PMID- 22390019
TI  - Creative midwifery education.

PMID- 22390020
TI  - Referral pathway for newly diagnosed cancer patients.

PMID- 22390021
TI  - Value added nurse recruitment and retention.

PMID- 22390022
TI  - Nurse education to cut cervical cancer.

PMID- 22390023
TI  - Work-ready graduate nurses.

PMID- 22390024
TI  - Emergency training boosts confidence.

PMID- 22390026
TI  - Nurse educators devalued drives change.

PMID- 22390025
TI  - SA e-learning expansion.

PMID- 22390027
TI  - The third space.

PMID- 22390028
TI  - [Analysis of serum T-lymphocyte subsets and NK cell activity in patients with
      squamous cell carcinoma of pharynx and larynx].
AB  - OBJECTIVE: To investigate the alteration of T-lymphocyte subsets and NK activity
      in patients with squamous cell carcinoma of pharynx and larynx. METHOD: T
      lymphocyte subsets and NK activity were determined by flow cytometry in 123
      patients with squamous cell carcinoma of pharynx and larynx. Blood samples of 36
      nontumor patients were used as control. RESULT: The total T lymphocytes were
      lower in patients with squamous cell carcinoma of pharynx and larynx than control
      group significantly (P < 0.05). The levels of helper lymphocyte subsets were
      little lower than those in control group(P > 0.05). On the other hand, the levels
      of suppressor lymphocytes in patients were higher than those in the control group
      (P < 0.05). Therefore, the CD4/CD8 ratios in patients were lower than those of
      the control group statistically (P < 0.05). There was no statistical difference
      in activated T lymphocytes and total B lymphocytes (P > 0.05), but NK activity in
      patients were lower than those in control group significantly (P < 0.01). There
      was no statistical difference in total T lymphocytes between stage I-II and stage
      III--IV (P > 0.05). The levels of helper lymphocyte subsets in stage I-II
      patients were little higher than in stage III-IV patients (P > 0.05), but the
      levels of suppressor lymphocytes in stage I-II patients were lower than in stage
      III-IV patients (P < 0.01). The CD4/CD8 ratios in stage I-II patients were
      significantly higher than in stage III-IV patients (P < 0.01). The levels of
      total B lymphocytes in stage I-II patients were significantly higher than in
      stage III-IV patients (P < 0.05). The activated T lymphocytes and NK activity did
      not changed statistically (P > 0.05). CONCLUSION: The immune function in patients
      with squamous cell carcinoma of pharynx and larynx is disordered and lower. With
      advanced stage disease, not only the cellular immune function in patients
      decrease gradually, but also the humoral immunity is lower. Analyzing T
      lymphocyte subsets and NK activity determined by flow cytometry would be easy and
      helpful to evaluate the immunologic condition of every patient.

PMID- 22390029
TI  - [Retrospective analysis of the treatment of recurrent congenital fistula or cyst
      in lateral cervical part].
AB  - OBJECTIVE: To analysis the therapeutic procedure on the recurrent congenital
      fistula or cyst in lateral cervical part. METHOD: Thirty-nine cases with
      recurrent congenital fistula or cyst in lateral cervical part were enrolled in
      this study including 12 cases from the first branchial cleft, 6 from the second
      branchial cleft and 21 from the third branchial cleft. RESULT: All the cases
      underwent fistula or cyst excision for 2 to 5 times in their whole therapeutic
      process, not counting the incision and drainage. During 9 months to 17 years
      follow-up, fistula or cyst in 6 cases relapsed,including 1 fistula from the first
      branchial cleft,3 fistulae from the second branchial cleft, 1 fistula and 1 cyst
      from the third branchial cleft, respectively. One case with recurrent fistula
      from the first branchial cleft was diagnosed temporal verrucous carcinoma six
      months after the third fistula excision operation and died one year after the
      forth operation probably due to the intracranial metastasis of temporal bone
      verrucous carcinoma. In two cases, the fistulae went through the thyroid gland to
      the piriform fossa and both the fistulae and part of the thyroid glands were
      resected. In the patients whose inner orificium fistulae were found and ligated
      effectively,no recurrence occurred during the followed-up period. CONCLUSION: The
      key point to cure the recurrent congenital fistula or cyst in lateral cervical
      part lies in proper occasion of operation, stain tracing in operation and
      reasonable program of operation.

PMID- 22390030
TI  - [Expression of matrix metalloproteinase-1, E26 transformation-specific-1 in
      laryngeal carcinoma tissue and the clinical significance].
AB  - OBJECTIVE: To investigate the expression of matrix metalloproteinase-1 (MMP-1),
      E26 transformation-specific-1 (Ets-1) in laryngeal carcinoma and to discuss their
      relevance and the roles in carcinogenesis and development of laryngeal carcinoma.
      METHOD: Immunohistochemical technique was used to detect the expression of MMP-1
      and Ets-1 protein in 34 tissues of laryngeal carcinoma and 34 para-carcinoma
      tissues, 15 cases of vocal cord polyps, and the use of the pathological image
      analysis software, we analysis the results of immunohistochemical semi
      quantitatively. RESULT: (1) The expression of MMP-1 and Ets-1 protein in
      laryngeal carcinoma tissues is obviously higher than that in para-carcinoma and
      in vocal cord polyps respectively (P < 0.05). There is no significant difference
      between the expression of para-carcinoma and vocal cord polyps(P > 0.05). (2) The
      expression of MMP-1, Ets-1 protein isn't related to patients' age and sex, tumor
      size,clinical classification (P > 0.05), but related to pathological grade,
      clinical stage and lymph nodes metastasis (P < 0.05). (3) There is a positive
      correlation between the expression of MMP-1 and Ets-1 in laryngeal carcinoma.
      CONCLUSION: Overexpression of MMP-1 and Ets-1 was observed in laryngeal
      carcinoma. The high expression of MMP-1 and Ets-1 may contribute to the
      carcinogenesis and development of laryngeal carcinoma,which is a important value
      to judge the malignant degree and progress of laryngeal carcinoma.

PMID- 22390031
TI  - [Analysis of clinical manifestations of rhinal and pharyngeal and laryngeal
      amyloidosis by 12 cases].
AB  - OBJECTIVE: To discuss the clinical characteristic of rhinal and pharyngeal and
      laryngeal amyloidosis. METHOD: Twelve cases of amyloidosis was confirmed,one case
      of multiple myeloma accompanied pharynx nasalis, laryngeal and facial amyloidosis
      was diagnosed and treated by chemotherapy in department of hematology; one case
      of plasmacytoma accompanied amyloidosis in right inferior turbinate concha was
      expected by nasal endoscope under local anesthesia and was treated by
      chemotherapy in department of hematology; five cases of polyps of vocal cord
      accompanied laryngeal amyloidosis were expected under self-retaining
      laryngoscope; three cases of local amyloidosis in bilateral vocal cords,
      subglottis and trachea were expected under self-retaining laryngoscope by
      polypotome and/ or CO2 laser; one case of pharyngeal amyloidosis in right tonsil
      was treated by tonsillectomy and the other case of local amyloidosis in lingual
      surface of epiglottis was expected by direct laryngoscope under general
      anaesthesia. RESULT: One case of multiple myeloma accompanied pharynx nasalis,
      laryngeal and facial amyloidosis died after 18 months because of cachexia
      accompanied pneumonia and multiple organ failure; one case of plasmacytoma
      accompanied amyloidosis in right inferior turbinate concha was relapse-free
      followed up for 2 years; five cases of polyps of vocal cord accompanied laryngeal
      amyloidosis were relapse-free followed up from 1 to 3 years one case of local
      amyloidosis in bilateral vocal cords, subglottis and trachea was relapse-free
      followed up for 3 years,another case of local amyloidosis in bilateral vocal
      cords, subglottis and trachea recurred in 4 months after operation and the other
      case recurred in 6 months after operation, these two recurrence cases of local
      amyloidosis in bilateral vocal cords, subglottis and trachea were treated again
      by operation and were relapse-free followed up for 6 months; two cases of
      pharyngeal amyloidosis (1 case of right tonsil amyloidosis and 1 case of local
      amyloidosis in lingual surface of epiglottis) were relapse-free followed up for 2
      years. CONCLUSION: The etiology of rhinal and pharyngeal and laryngeal
      amyloidosis is related to multiple factor. The clinical manifestations of rhinal
      and pharyngeal and laryngeal amyloidosis is complicated and non-specificity. To
      distinguish the clinical manifestations of primary amyloidosis (locality and
      general), secondary amyloidosis (locality and general), amyloidosis associated
      multiple myeloma and heredofamilial amyloidosis is important in diagnosis and
      treatment to reduce diagnostic errors.

PMID- 22390032
TI  - [Case-control study on risk factors of laryngeal cancer in Heilongjiang
      province].
AB  - OBJECTIVE: To study the incentives of laryngeal cancer in Heilongjiang province.
      METHOD: A 1:One matched case control study was used to study the risk factors of
      laryngeal cancer in Heilongjiang province, distributing all tested staff by the
      same gender, age, urban and rural. Logistic regression models were used to
      analysis the relationship. RESULT: In single Logistic regression models, such
      habit as high levels of education, frequently consumption of sauerkraut, BBQ
      food, processed meats, the less physical activity, a relatively short time,
      smoking, irascible, and other factors would increase the risk of suffering from
      laryngeal cancer. But regular consumption of fresh vegetables, coarse grains,
      eggs, milk, and regular physical activity would reduce the risk of suffering from
      laryngeal cancer. The odds ratios (OR) were calculated using multiple Logistic
      regression models, ORs for the highest versus the lowest quintile of intake were
      15.502 0 for high levels of education. 8.012 0 for smoking frequently. 7. 2680
      for eating sauerkraut. 2.904 0 for eating BBQ food. 0.408 0 for exercise in
      protective factors. CONCLUSION: Potential risk factors for laryngeal cancer were
      eating sauerkraut. BBQ food and smoking frequently, but proper exercise may
      reduce the risk of laryngeal cancer.

PMID- 22390033
TI  - [Study on influence of thermoplastic mask on radiation dermatitis for patients
      with laryngeal cancer].
AB  - OBJECTIVE: To observe the protective effect of thermoplastic mask on radiation
      dermatitis for patients with laryngeal cancer. METHOD: Seventy-three patients
      with laryngeal cancer was recruited in the research and were divided into two
      group. The test group (38 patients) was treated with opening-window on
      thermoplastic mask to protect the skin exposure to the radiotherapy. The control
      group (35 patients) was treated with intact thermoplastic mask. The rate of radio
      dermatitis and pain in the skin exposure to the radiotherapy were assessed.
      RESULT: The radio-dermatitis and pain of the skin exposure to the radiotherapy in
      the test group was significantly lower than the control group (P < 0.05).
      CONCLUSION: The opening-window on thermoplastic mask can decrease the radio
      dermatitis for patients with laryngeal cancer.

PMID- 22390034
TI  - [Study about eye complication of nasopharyngeal carcinoma].
AB  - OBJECTIVE: To explore the eye complication of nasopharyngeal carcinoma (NPC), to
      analysis the clinical manifestation, CT characteristics and pathological
      diagnosis of eye complications of NPC and to provide the base for early diagnosis
      of NPC. METHOD: To retrospectively study of 82 cases eye complications in 562
      cases NPC, to study their clinical manifestation, CT characteristics and
      pathological diagnosis. RESULT: The clinical studies showed that eye complication
      cases were occurred in 82 cases of 562 NPC cases (14.6%). Thirty-six cases in
      left and 37 cases in right eye, 9 cases in bilateral eyes. Sixty-five cases came
      from Guangdong, while the others 17 cases come from 5 provinces. There were 9
      kinds of eye manifestation. CT appearances: 40 cases suffered from skull base
      distracted, 6 cases with orbit involved, 2 cases ( in left eyes) with orbit
      metastasis, 12 cases with nose-sinus involved, 68 case with parapharyngeal space
      involved, 49 cases with soft issue in wall of styloid process involved (there
      were many kind of shows in the same case, so the data were repeated in these
      cases). CONCLUSION: There were multiplicity and complexity in eye complication of
      NPC. Ophthalmologists should think highly of these cases.

PMID- 22390035
TI  - [The influence of denervation on myofiber morphology of the adductor and abductor
      in patients with recurrent laryngeal nerve paralysis].
AB  - OBJECTIVE: To investigate the influence of denervation on myofiber morphology of
      the adductor and the abductor in patients with recurrent laryngeal nerve (RLN)
      paralysis and to provide experimental evidence for the clinical feasibility of
      RLN repair. METHOD: Adductor muscles were acquired from the lateral
      cricoarytenoid muscle (LCAM) and abductor muscles from the posterior
      cricoarytenoid muscle(PCAM). Normal human PCAM and LCAM are treated as control
      group (n = 7). Thirty-eight cases of PCAM with damaged RLN were divided into five
      groups according to the duration of their RLN damage: 0.5-1 year (7 cases), > 1-2
      years (10 cases), > 2-3 years (8 cases), > 3-6 years (8 cases) and > 6 years (5
      cases); twenty-nine cases of LCAM were also divided into five groups: 0.5-1 year
      (7 cases), > 1-2 years (6 cases); > 2-3 years (6 cases), > 3-6 years (6 cases)
      and > 6 years group(4 cases). They were all stained with HE and Masson three
      color staining, the fiber cross-sectional area of muscle tissue and collagen
      connective tissue were quantitative analyzed. The changes of myofiber morphology
      of adductor and abductor muscles after the loss of the RLN were analyzed with
      image analysis system. RESULT: The transverse areas of myofibers gradually
      decreased and those of collagen fibers gradually increased with the prolongation
      of denervation. (1) Difference between the denervated groups of LCAM of 0.5-1
      year, > 1-2 years and > 2-3 years groups were not significant (P > 0.05). Fiber
      cross-sectional area of > 3-6 years group decreased most obviously with
      significantly difference compared with > 2-3 years group (P < 0.05); (2) There
      were obvious difference between the control group, 0.5-1 year group, > 1-2 years
      group, > 2-3 years group and > 3-6 years of PCAM(P < 0.05); (3) There was no
      significant difference between the group of > 3-6 years and > 6 years of two
      kinds of laryngeal intrinsic muscle (P > 0.05); (4) Fiber cross-sectional area of
      each group of the LCAM after 1 year denervation were significantly greater than
      that of the PCAM under same conditions (P < 0.05). CONCLUSION: The influence of
      denervation on myofiber morphology following denervation is different between the
      abductor and adductor owing to the different fiber type composition and
      functional properties. The rate of muscle atrophy of the adductor is slower than
      that of the abductor. To restore the structure and function of denervated
      laryngeal muscles better, the recurrent laryngeal nerve injury repair surgery for
      PCA muscle function recovery should be carried out within 1 year after
      denervation while the surgery for LCA muscle function recovery should be carried
      out within 3 years after denervation.

PMID- 22390036
TI  - [The short duration functional electrical stimuli do not cause mRNA expression
      change of K(ATP) channel and acute inflammation cytokine in recurrent laryngeal
      nerve].
AB  - OBJECTIVE: To investigate whether the inflammation response and K(ATP) channel
      damage happened because of acute injury after functional electrical stimuli (FES)
      act on the recurrent laryngeal nerve (RLN). METHOD: Thirty rabbits were divided
      into 3 groups by 10 rabbits for each group. The unilateral RNL were stimulated by
      FES with cuff electrode in first group. There was electrode on the RNL without
      FES in second group. The third group was normal control. The electrical generator
      and isolation unit provide electrical stimulation to the RLN at 50 Hz, with 4 mA
      current, for 2ms pulse duration. The total train duration was 5 seconds (2
      seconds on; 3 seconds off). The RLN were collected in 1 hour after 3 hours
      electrical stimuli. We measured mRNA expression of injury acute response
      inflammation cytokine IL-10, TGF-beta1, TNF-alpha and K(ATP) Subunit protein
      Kir6.1, Kir6.2, SUR2AB, using real-time reverse transcribed-polymerase chain
      reaction. PCR products were verified by electrophoresis in agarose gels. We
      investigated the vocal synchronic adductive movement with RLN FES by endoscopy.
      We investigated the nerve local RNL morphological burn. Data were analyzed with
      the One-way ANOVA analysis of SPSS version 13.0 for Windows. RESULT: There were
      no significance difference among three groups in mRNA expression of inflammation
      cytokines IL-10, TGF-beta1, TNF-alpha and K(ATP) channel protein Kir6.1, Kir6.,
      SUR2AB. We did not find the nerve morphological burn in all rabbits RLN. The
      vocal synchronic adductive movement were normal during stimuli time. CONCLUSION:
      The short duration functional electrical stimuli do not cause mRNA expression
      change of K(ATP) channel and acute inflammation cytokine in recurrent laryngeal
      nerve.

PMID- 22390037
TI  - [Construction of lentivirus vector of interference of EGFL7 gene and its
      inhibitive role on the invasion of laryngeal cancer cell].
AB  - OBJECTIVE: To construct a lentivirus vector of RNA interference (RNAi) of EGFL7
      gene and observe its inhibitive role on the invasion of laryngeal cancer cell.
      METHOD: The effective sequence of siRNA targeting EGFL7 gene was confirmed. Both
      sense and antisence Oligo DNA of the targeting sequence was designed, synthesized
      and cloned into the pLV vector,which contained H1 promotor and green fluorescent
      protein (GFP). The resulting lentivirus vector containing EGFL7 shRNA was called
      LV-sh EGFL7,and it is confirmed by PCR and sequencing. After that, EGFL7 shRNA
      was transfected into Hep-2 cells and Western blot was used to test the expression
      of EGFL7. At last, boyden chamber was used to observe the invasion of the Hep-2
      cells. Colony formation assay using a EGFL7 gene silencing on the Hep-2 cell
      colony forming ability. RESULT: PCR and DNA sequencing demonstrated that the
      lentivirus RNAi vector of EGFL7 (LV-sh EGFL7) producing EGFL7 shRNA was
      constructed successfully. The titer of concentrated virus was 5 x 10(8) TU/L.
      Western blot showed that the expression of EGFL7 was negative in the EGFL7 siRNA
      Hep-2 cells. And boyden chamber showed the invasive capability of Hep-2 cells
      transfected EGFL7 siRNA were obviously decreased. EGFL7 gene silencing of cell
      colony formation rate of cloned Hep-2 cells and compared with empty vector cells,
      cell cloning and colony formation was significantly reduced. CONCLUSION: The
      lentivirus RNAi vector of EGFL7 was constructed successfully. And EGFL7 silence
      can inhibit invasion of laryngeal cancer in vitro. After silence EGFL7, Hep-2
      cell colony formation was significantly lower, that is, gene expression can be
      down EGFL7 some extent laryngeal cancer cells inhibited anchorage independent
      growth capacity.

PMID- 22390038
TI  - [Identification of infection agent in diagnostic material from patients with
      suspicion of enteroviral meningitis].
AB  - Clinical diagnosis of enteroviral infections of the central nervous system are
      performed by virus isolation in sensitive cell lines and RT-PCR assay. The aim of
      the study was evaluation these techniques for fast diagnosis meningitis caused by
      enteroviruses. 69 samples (cerebrospinal fluid, CSF) were collected and analised
      by RT-PCR reaction. 39 samples were positive (56.5%). 20 positive sample were
      selected and simultaneously 20 stool samples from the same patients were
      collected for virus isolation in sensitive cell line. Positive isolation was
      observed only in one CSF (5.3%) and in 9 stool samples (45%).

PMID- 22390039
TI  - [Epidemiological situation of children' intestinal infections in Malopolska
      Voivodeship regarding to new possibilities of rotavirus prevention].
AB  - Rotavirus is the main etiological cause of intestinal infections in children. The
      voluntary rotavirus vaccines was included to Polish vaccination schedule in 2007.
      The aim of this study was assessment of epidemiological situation of intestinal
      infections in children up to two years in Malopolska Voivodeship regarding the
      population influence of rotavirus vaccinations on the number ofrotavirus
      infections. For entire area included to evaluation, despite the increasing
      vaccination coverage in children the number of notified rotaviruses infections
      revealed the rising trend, as well. The results have not showed the population
      influence of voluntary rotavirus vaccinations on the incidence of intestinal
      infections in the youngest children.

PMID- 22390040
TI  - [Dengue as haemorrhagic fever].
AB  - Dengue virus is distributed in tropical and subtropical regions and transmitted
      by mosquitoes of the genus Aedes. In September 2010 two cases of indigenous
      dengue fever were diagnosed in metropolitan France for the first time and next
      DENV infection was diagnosed in a German traveler returning from a trip to
      Croatia. The Aedes albopictus mosquitoes were found in several European countries
      (for example in greenhouses in Netherlands). The indigenous DENV infections in
      Europe are rare diseases, probably acquired after bites of infected mosquitoes
      imported by airplanes from endemic areas. Nonspecific symptoms including: fever
      (up to 39 degrees C), chills, arthralagia, headache, myalgia and abnormalities in
      laboratory tests such as: thrombocytopaenia, leukopaenia and liver tests cause
      problems with differential diagnosis ofhematologic and hepatologic syndromes. The
      most serious complications are associated with dengue shock syndrome with
      mortality rate of 50%.

PMID- 22390041
TI  - [Dengue in patients hospitalized in the hospital ward of zoonoses and tropical
      diseases in Warsaw in years 2002-2011].
AB  - The article presents the clinical course of Dengue in 22 patients hospitalized in
      the Ward of Tropical Diseases and Zoonoses in Warsaw in 2002-2011. Dengue belong
      to hemorrhagic fevers.The virus which causes dengue (DENV) belonging to the
      Flaviviridae family of RNA viruses. It is transmitted by arthropods (mosquitoes
      Aedes). Among the hospitalized patients most aged 20-30 years (10 people), there
      were more women than men. There were two foreigners from Asia and Central
      America. The majority of patients visited regions of South East Asia (Thailand,
      Laos, Vietnam) then India, Brazil and Mexico. Most of hospitalized people had
      light and average course. Symptoms of the disease usually occurred shortly after
      returning from the visited region and were not specific (flulike). In of one of
      the patients the course was very heavy. The average hospital stay was 9 days, the
      longest, in one person was 27 days. All patients were treated symptomatically,
      one person received a platelet transfusion twice without complications. Two
      people were treated with steroid drugs. All patients were discharged without
      serious consequences for health and life.

PMID- 22390042
TI  - [Ticks infected with bacteria pathogenic to humans in municipal parks in Warsaw].
AB  - The aim of the study was to detect bacteria pathogenic to humans, such as
      Borrelia burgdorferi sensu lato, Rickettsia spp, and Coxiella burnetii in ticks
      found in municipal parks in Warsaw, including The Royal Lazienki Park, Mokotow
      Fields, Jozef Sowinski Park, Ujazdow Park and Fort Bema Park. To detect
      microorganisms PCR technique was used. It was shown that 6.1% of the ticks in
      Warsaw's parks are infected with B. burgdorferi sensu lato, and 2.9% with
      Rickettsia spp. Analysis of sequencing results revealed in examined ticks the
      presence of B. burgdorferi sensu stricto and R. helvetica.

PMID- 22390043
TI  - [Case of TIBOLA/DEBONEL (tick - borne lymphadenopathy/Dermacentor spp. - borne
      necrosis - erythema - lymphadenopathy) in Poland].
AB  - Rickettsia slovaca was recognized as the causative agent of the disease named
      tick - borne lymphadenopathy (TIBOLA) or Dermacentor spp.- borne necrosis -
      erythema lymphadenopathy (DEBONEL). Generally, this ricketsiosis is considered a
      mild disease but the disease is considered a mild rickettsiosis, but severe
      symptoms can appeare, especially in untreated patients. Described infection is
      the first case of TIBOLA/DEBONEL found in Poland. The patient had typical
      symptoms, such as enlarged painful cervical lymph nodes and maculo - papular
      rash. Milium on the scalp behind the ear concha, was a probably scar formation
      associated with typical eschar. The diagnosis was confirmed by detection of 128
      titer in MIF tests with R. rickettsii and R. slovaca antigens and four-fold
      decrease after treatment.

PMID- 22390044
TI  - [Serological confirmation of the prevalence of tick-borne encephalitis virus
      among patients with neurological infections in the Warmia-Masuria province in
      2006-2010].
AB  - The aim of the study was to analyze of tick-borne encephalitis (TBE) in the
      Warmia-Masuria province on the basis of serological testing of 878 patients with
      symptoms of neurological infections, diagnosed in 2006-2010 in the Voivodeship
      Sanitary-Epidemiological Station in Olsztyn. Specific IgM and IgG antibodies
      against the TBE virus were detected in serum and cerebrospinal fluid samples by
      ELISA method. Percentage of persons with serologically confirmed TBE was 15.5%.
      This confirms contact with TBE virus and its role as the suspected cause of
      neurological infections in patients in the Warmia-Masuria province. Men and
      people over 46 years of age were more commonly seropositive. Among examined
      patients the percentage of seropositive men was 18.1% and the proportion of
      seropositive women was - 12.9%. Most positive results were found in patients
      between 46 and 50 years of age (20.7%) and in those aged 56-60 years (19.5%).
      Seasonal patterns were detected, with highest proportion of seropositive results
      in July, August and October.

PMID- 22390045
TI  - [Cases of Toxoplasma gondii infection in foetus's and toxoplasmic encephalitis in
      immunosupressed patients confirmed by PCR method in NIPH - NIH, 2009-2010].
AB  - The results of molecular tests for Toxoplasma gondii infection carried out in
      NIPH-NIH were presented in the light of current data on diagnostics and
      epidemiology of toxoplasmosis. Between January 2009 and December 2010 four cases
      of active toxoplasmosis were confirmed using PCR targeting the 529-bp repeat
      element of Toxoplasma gondii. Intrauterine infection was found in 3 out of 180
      (1.7%) examined women. Toxoplasmic encephalitis was confirmed in one patient who
      was a liver transplant recipient. T. gondii was not detected in cerebrospinal
      fluid of 19 out of 20 examined patients with encephalitis. The cases of
      intrauterine toxoplasmosis diagnosed in 2009-2010 make 57.1% of all cases
      diagnosed in the last decade. In 2001-2010 toxoplasmic encephalitis was detected
      in two patients out of 45 examined. The choice of tests and interpretation of the
      results are important elements of T. gondii infection diagnosis and require
      cooperation between clinicians and laboratory diagnosticians. Establishing
      reference center for toxoplasmosis in Poland would contribute towards the
      improvement of standards of diagnostics and treatment of cases of congenital
      infections and the infection in immunosuppresed patients.

PMID- 22390046
TI  - Parasitological stool examination from children without the typical symptoms of
      parasitic disease.
AB  - Most parasitic intestinal infestations in humans are sub-clinical and, therefore,
      they are rarely diagnosed. A number of general, non-specific symptoms of
      parasitic invasions are often attributed to other diseases. A parasitological
      examination of feces performed as part of this study confirmed the presence of
      intestinal parasites in 21.6% of samples. Among the patients who reported 6
      different symptoms, the percentage of parasite-positive samples reached 80%. The
      obtained results suggest that coproscopic tests may establish the diagnosis in
      unclear cases, particularly in children. Many parasitic invasions are zoonoses
      and pets owe a reservoir. In view of the above, the results for pet owners and
      non-pet owners were compared in the study. There was no direct correlation
      between pet ownership and the incidence of parasitic infections.

PMID- 22390047
TI  - [Clinical aspects and treatment of respiratory syncytial virus infection in
      infants in the first 6 months of life].
AB  - Respiratory viral infection are one of the most frequent problem in infant and
      the younger children. Respiratory syncytial virus infects nearly all children (75
      100%) in the first 36 months of life. AIM: Analysis of clinical aspects and
      treatment of respiratory syncytial virus infection in infant hospitalized in year
      2009-2010 in Department of Pediatrics Propedeutics and Bone Metabolism Diseases.
      METHODS: Medical documentary of 32 infants in the first 6 months of life was
      analysed. RESULTS: The most frequent clinical symptoms were increased dyspnoea -
      in 96.88% children and discharge in respiratory tract - in 78.13% children. In
      near all patients (93.75%) antibiotic was used in treatment and Budesonid was
      applied in 87.5% children. Infants with Respiratory syncytial virus infections
      were hospitalized because of increased dyspnoea. Antibioticotherapy used in the
      examinated infants prevented complications.

PMID- 22390048
TI  - [Cases of children with influenza AH1N1/2009 in the district of Lodz in two
      epidemic waves].
AB  - High influenza morbidity due to new antigenic strain AH1N1 was announced in
      Mexico in spring 2009. Influenza pandemic caused by the virus AH1N1/2009 spread
      around the world. Two pandemic waves were noted in most European countries: the
      first one was due to summer months migration, the second wave started in the
      beginning of common influenza season. We present features of both waves in
      children from the district of Lodz. We describe mild clinical course in 14
      children who came from holiday in Spain with influenza and who were hospitalized
      and treated with osltamimivir due to unpredictable course of new influenza. We
      also present 22 influenza cases of the autumn pandemic wave, when children with
      severe complications of influenza and children from high risk groups were
      hospitalized and treated with antivirals. Experience that we have gained during
      2009 influenza pandemic indicates that International Influenza Control System is
      very efficient, however more flexibility is required in application of treatment
      and prophylaxis procedures with new influenza strains. Applied methods of control
      should mostly depend on the virulence of pandemic strain.

PMID- 22390049
TI  - [Polish multicenter study on safety and efficacy of adefovir dipivoxil in the
      treatment of lamivudine resistant chronic hepatitis B in adults (HEP 2008)].
AB  - Initiated in April 2008 Polish multicenter study HEP2008 aimed clinical data
      concerning safety and efficacy of adefovir dipivoxil (ADV, Hepsera, Gilead
      Sciences) in adult chronically infected HBV with lamivudine (LAM) resistance
      after earliest treatment. We examined 38 men (70.4%) and 16 women (29.6%) with
      chronic hepatitis B in age 23-81 (average 53) mostly HBeAg positive (70.4%).
      Majority of patients received earlier LAM (72%), but others additional entekawir
      and? or pegylated interferon. Average time from discovering infection HBV was 95
      +/- 77 (10-307) months. Majority of patients received monotherapy ADV, but
      physicians decided at 12 (22%) persons about continuation of LAM therapy. Median
      HBV DNA level decreased from a baseline value 6.73 +/- 1.71 (1.8-9.0) to 3.25
      log10 copies/mL. At least HBV DNA drop 1 log10 and 2 log10 get 78.8 and 60.6% in
      24 week, 84.8 and 69.7% in 48 week. HBV DNA reduction below level 300 and 50
      copies/mL it observed in 15.2 and 6.1% in 24 week, 39.4 and 30.3% in 48 week.
      Patients with undetectable Mean ALT activity dropped significantly and were below
      limit norm at 24 week in 40%, and at 48 week in 58% of patients. Patients treated
      ADV and LAM reached great reduction of ALT activity but was no influence on HBV
      DNA reduction. Results of research have confirmed efficiency and safety 48-week's
      therapy ADV in patients with LAM resistance.

PMID- 22390050
TI  - [Efficacy and safety of vaccines against tuberculosis in the relation to genetic
      variability of Mycobacterium bovis BCG strains].
AB  - All vaccines against tuberculosis used actually over the world contain
      Mycobacterium bovis BCG strains (Bacillus Calmette-Guerin) as active substance.
      Strain BCG, that was obtained in 1921 by Calmette and Guerin after 13 years
      ofpassaging on the potato-glicerol medium with addition of bile, was distributed
      to many laboratories for vaccine production. The repeated passages of M. bovis
      BCG strain in different culture conditions caused the numerous mutations and
      formation of many BCG substrains that differed according to efficacy and safety.
      The review of many publications related to genetic differences between BCG
      substrains was performed for identify the genes responsible for their virulence
      and protective characteristics. Possibility of development of new generation
      vaccines against tuberculosis is discussed.

PMID- 22390051
TI  - [Number of vaccinations performed and immunological system].
AB  - The study did not support the hypothesis of a causal link between vaccinations
      and chronic diseases and autoimmune diseases. Vaccinations do not weaken the
      immune system. A man can produce about 10 billion different antibodies. During
      the lifetime human organism produces from 1 to 100 million different antibodies.
      Vaccination creates antibodies to about 150 antigens. We describe the capacity of
      the infant's immune system to respond to vaccines as well as discuss the
      plausibility of theories that relate vaccines to the development if specific
      chronic disease.

PMID- 22390052
TI  - [Public health in Poland before World War II--lesson learned].
AB  - The article discusses the most important legal acts regulating the activities of
      the institutions of public health in interwar period in Poland. Particular
      attention was paid to the Ministry of Public Health, municipal boards, the Office
      of the Extraordinary Commissioner for Combating Epidemics and the National
      Institute of Hygiene. The substantive scope of the Basic Sanitary Act of 19 July
      1919 was presented. The scope of the Act was compared with 10 essential public
      health services as defined in 1994 in the U.S.A. A significant compatibility of
      views on public health in the past and present-day was reported. It was recalled
      that after World War II in Poland public health issues have been scattered into
      numerous acts. It was proposed to regard the Basic Sanitary Act as a hint when
      creating a present, a comprehensive law on the public health system.

PMID- 22390053
TI  - [The activity of the State Sanitary Inspectorate after implementation of the act
      of January, 23 2009 "Amending certain acts regarding reorganization and
      redistribution of competences of the public administration at the provincial
      level"].
AB  - The restructuring of the State Sanitary Inspectorate was determined by the need
      to adjust the existing system to the new structure- and task-oriented standards
      introduced by the administrative reforms at the provincial level. This brought
      about a lot of changes in the way State County Sanitary Inspectors operate. For
      first few months after the enforcement of the Act of January 23.2009 amending
      certain acts regarding reorganization and redistribution of competences of the
      public administration at the provincial level (Journal of Laws, No. 92, item.
      753, 2009) brought about a lot of ambiguities and expectations. Such unresolved
      issues are typical for the initial or transition period after implementation of a
      new law. The approach to the operation of the State Sanitary Inspectorate at the
      county level depicted in the article lays the emphasis on the challenges in the
      legal and task-oriented domain that arose after coming into force of the
      aforementioned amendment. By way of conclusion, the authors of the article
      briefly summaries the practical outcomes of the transformations undergone by the
      State Sanitary Inspectorate at the county level.

PMID- 22390054
TI  - [Globalization and infectious diseases].
AB  - Globalization is a phenomenon characteristic of present times. It can be
      considered in various aspects: economic, environmental changes, demographic
      changes, as well as the development of new technologies. All these aspects of
      globalization have a definite influence on the emergence and spread of infectious
      diseases. Economic aspects ofglobalization are mainly the trade development,
      including food trade, which has an impact on the spread of food-borne diseases.
      The environmental changes caused by intensive development of industry, as a
      result of globalization, which in turn affects human health. The demographic
      changes are mainly people migration between countries and rural and urban areas,
      which essentially favors the global spread of many infectious diseases. While
      technological advances prevents the spread of infections, for example through
      better access to information, it may also increase the risk, for example through
      to create opportunities to travel into more world regions, including the endemic
      regions for various diseases. The phenomenon ofglobalization is also closely
      associated with the threat of terrorism, including bioterrorism. It forces the
      governments of many countries to develop effective programs to protect and fight
      against this threat.

PMID- 22390055
TI  - [Five-year relative survival rates in Swietokrzyskie voivodeship (Poland) on the
      basis of the Swietokrzyskie Cancer Registry data].
AB  - The aim of the study was to evaluate the 5-year relative survival rates of
      patients with all malignant cancers in the Swietokrzyskie Voivodeship who were
      diagnosed with cancer during the period 1995-2007, which is when the
      Swietokrzyskie Cancer Centre began and developed its comprehensive oncological
      care in the region. 41,104 patients from the Swietokrzyskie Voivodeship who were
      registered in the Swietokrzyskie Cancer Registry in that period of time were
      included in the analysis of the survival rates. Relative survival was calculated
      using the Hakulinen and Brenner methods. These methods are recommended by the
      European Network of Cancer Registries for the population-based cancer registries
      where cause of death is unknown. The results were referred to the European
      average of relative survival rates calculated for all malignant cancers combined,
      as well as selected cancers calculated within the EUROCARE-4 project. The
      survival rates of patients diagnosed from 2003 to 2007 do not differ
      significantly from the European average, and are even higher for both sexes
      combined (56.0% v. 48.3%), and cancers of cervix and corpus uteri, as well as
      lung cancer for men and women combined. The 5-year relative survival rates for
      all malignances of patients in the Swietokrzyskie Voivodeship diagnosed from 2003
      to 2007 increased by 9.7 percentage points in comparison to previous years 1995
      2002. A significant improvement was seen in prostate cancer (28.1 percentage
      points), rectum cancer (13.1) and colon cancer (11.0). The improvement of the
      survival rates reflects the improvement in curability due to the development of
      the Swietokrzyskie Cancer Centre.

PMID- 22390056
TI  - [An analysis of kindergarden teachers' preparation to provide first aid].
AB  - The major causes of deaths among preschool children are injuries and poisoning.
      Among the injuries, the most frequent are road accidents and accidents on farms.
      We may also find health and life risks to preschoolers in homes and education
      centres. Everybody should know first-aid rules and how to apply them in life
      threatening situations. This duty particularly concerns kindergarten teachers.
      The purpose of the work was an analysis of kindergarten teachers' preparation to
      provide first aid. The research was performed on a sample of 100 kindergarten
      teachers from the Lubelskie Province. The research took place in January and
      February 2011 with the use of questionnaires prepared in-house The analysis of
      the results indicated that most teachers (84% of respondents) had participated in
      the first-aid training courses. The teachers with job seniority below 10 years
      and those between 11 and 20 years' seniority took part more often in the first
      aid training courses than the respondents with seniority above 20 years (p=0,02).
      Respondents, in most cases, assessed their knowledge of first aid at grade 3 (in
      a continuum from 1 to 5) (42% of respondents)--the average grade was 2.98 +/-
      0.97.

PMID- 22390057
TI  - [Occurrence of head pediculosis and its control in children's homes in selected
      provinces of Poland in the years 2007-2009].
AB  - Despite civilisation development and the easy access to pediculicides, head
      pediculosis remains still the social, hygienic and medical problem. In the years
      2007 - 2009 in children's homes in selected provinces of Poland the questionnaire
      survey on the occurrence of head pediculosis and its control have been conducted.
      From 127 orphanages 61 (48.03%) sent back fulfilled questionnaire. The
      infestation level ranged from 4.63% (Swietokrzyskie Province, 2009) until 17.63%
      (Mazowieckie Province 2007) in the surveyed children's homes. The most head
      pediculosis cases were observed among girls 6 - 12 years old in children's homes
      from all regions investigated. The profile of pediculicides used had been changed
      during our study: in the first year the most often pediculicides with the
      insecticide permethrin were used. In the next years their use decreased, but the
      use of herbal and silicone pediculicides increased. The efficacy of anti-louse
      product was the most important factor for the respondents when they choose an
      pediculicide.

PMID- 22390058
TI  - [Score method evaluation of the sanitary condition of the University Hospital in
      Bydgoszcz and personnel education in 2007 - 2010].
AB  - The Quality Management System ISO 9001:2008 introduced by the Management Board of
      the hospital in the year 2007 resulted in change of the methods used by the
      Hospital Infection Control Team (HICT) to assess the sanitary-and-hygienic
      condition. The inspection protocol used by HICT was modified as part of the
      Quality Management System. It was supplemented by the score sheet which made the
      inspection results more objective. The purpose of the study was to assess the
      results of the supervision over the sanitary and epidemiologic condition of the
      hospital as well as personnel training carried out in the years 2007-2010 by the
      Hospital Infection Control Team (HICT) of Szpital Uniwersytecki nr 2 im. dr.
      J.Biziela (J.Biziel University Hospital no. 2). 407 inspection protocols issued
      in the years 2007-2010 were analysed. The sanitary/hygienic condition indicators
      and personnel education indicators were calculated based on the analysed data.
      The sanitary/hygienic condition indicator for the entire hospital in the years
      2008-2010 amounted to over 91.50% and only in the year 2007 it was 89.33%. While
      the personnel education indicator for the entire hospital increased from 90.35%
      in 2007 to 93.75% in 2010. CONCLUSIONS: the assessment of hospital units
      performed on the basis of the new protocol of the sanitary/hygienic condition has
      been proven in practice, i.e. insufficient personnel education as regards
      hospital hygiene is efficiently detected by HICT at individual workstations and
      the Management Board of the hospital is notified on the ongoing basis on the
      results of supervision provided by HICT.

PMID- 22390059
TI  - [Waste generated in Polish hospitals during the years 2005 - 2009].
AB  - The medical institutions generate mainly municipal and medical waste. The medical
      waste includes infectious waste, dangerous but not infectious waste (toxic) and
      medical not dangerous waste. They have to be correctly identified, properly
      sorted and suitably neutralized. Questionnaires investigations were conducted on
      the basis on the forms worked out at National Institute of Public Health -
      National Institute of Hygiene. Information from above seven hundred seventy
      hospitals were collected. Inquiries indicated that during the period of years
      2005-2009 over two hundred thousand beds per year were available. The degree of
      the use run from 52% to 100%, in average 72%. The largest fraction of the waste
      from all institutions were municipal waste run from 80% to 90%. Dangerous waste
      in following years were between 9.9% and 18.1%. The great part of dangerous waste
      were infections waste, which content ranged from 8.7 to 17.1%. Very low quantity
      of medical not dangerous waste was noted (1-1,7%). The majority of infectious
      medical waste were neutralized outside hospitals by the companies having suitable
      permissions. The thermal conversions (burning) was the most often used method.

PMID- 22390060
TI  - [Department of epidemiology of the National Institute of Hygiene in Warsaw in the
      years 1951-2011--origins of forming, developmental ways in 60 years of work].
AB  - The paper discussed the origins of forming in 1951 the Department of
      Epidemiology, National Institute of Hygiene in Poland and its subsequent tasks.
      Relating to the evolving tasks, changes in the organizational structure,
      professional profile of the staff, main professional challenges and scientific
      achievements are described in 10 years cycles. Successive chapters address:
      scientific careers of the Department staff and contribution to scientific
      development of the whole institute among others; teaching and training, mainly
      targeted at the epidemiological service staff in Poland; editorial and publishing
      activities.

PMID- 22390061
TI  - Urinary tract infections of Escherichia coli strains of chaperone-usher system.
AB  - Urinary tract infections are a very serious health and economic problem affecting
      millions of people each year worldwide. The most common etiologic agent of this
      type of bacterial infections, involving the upper and lower urinary tract, are E.
      coli strains representing approximately 80% of cases. Uropathogenic E. coli
      strains produce several urovirulence factors which can be divided into two main
      types, surface virulence factors and exported virulence factors. Surface-exposed
      structures include mainly extracellular adhesive organelles such as fimbriae/pili
      necessary in adhesion, invasion, biofilm formation and cytokine induction. Among
      the surface-exposed polymeric adhesive structures there are three most invasive
      groups, type 1 pili, type P pili and Dr family of adhesins which are bioassembled
      via the conserved, among Gram-negative bacteria, chaperone-usher secretion
      system. Type 1 and P-piliated E. coli cause cystitis and pyelonephritis. The Dr
      family of adhesins recognizing DAF receptor is responsible for cystitis,
      pyelonephritis (especially in pregnant women) and diarrhoea (in infants). In
      addition, Dr-positive E. coli strains carry the risk of recurrent urinary tract
      infections. Pyelonephritis in pregnant women leads to a series of complications
      such as bacteremia, urosepsis, acute respiratory distress syndrome and even
      death. In the era of increasing drug resistance of bacteria, the development of
      vaccines, drugs termed pilicides and inhibitors of adhesion may be a promising
      tool in the fight against urogenital infections.

PMID- 22390062
TI  - Gelatinase-associated phenotypes and genotypes among clinical isolates of
      Enterococcus faecalis in Poland.
AB  - Enterococcus faecalis is an important nosocomial pathogen causing serious
      invasive infections. One of the virulence factors of this pathogen, gelatinase
      GelE, is a protease whose gene expression is regulated by the Fsr quorum sensing
      system. In this study, we used a well-characterized collection of 153 clinical E.
      faecalis isolates to investigate the distribution of genes involved in gelatinase
      expression. Although 140 isolates (91% of the group) harbored the gelE gene, only
      81 isolates (53%) produced active gelatinase. The gelatinase-negative phenotype
      was found in several unrelated clones, and appeared to be caused by various
      genetic events. Isolates of the hospital-adapted clonal complex 2 (CC2) and of
      CC40 were uniformly gelatinase-positive, while all the CC87 isolates contained
      the 23.9 kb deletion encompassing most of the fsr locus and were gelatinase
      negative. No significant differences among isolates of different clinical origin
      and gelatinase activity or presence of the fsr genes were found with the
      exception of isolates from cerebrospinal fluid, which were more often gelatinase
      positive than colonizing isolates.

PMID- 22390063
TI  - Identification and characterization of the Trichoderma harzianum gene encoding
      alpha-1,3-glucanase involved in streptococcal mutan degradation.
AB  - alpha-1,3-Glucanases (mutanases) are currently of great interest due to their
      potential use in the field of dental care. These enzymes have been reported in
      several bacteria, yeasts and fungi, but up to now, characterization of this
      family of proteins has been relatively poor. In this study, we identify and
      characterize a mutanase gene from Trichoderma harzianum CCM F-340. Sequence
      analysis, on the nucleotide and amino acid levels reveals that this alpha-1,3
      glucanase is highly homologous to alpha-1,3-glucanases from T harzianum isolate
      CBS 243.71 and T asperellum CECT 20539. T. harzianum CCM F-340 mutanase is a 634
      aa residue protein with a calculated molecular mass of 67.65 kDa, composed of two
      distinct, highly conserved domains (a long N-terminal catalytic domain and a
      short C-terminal polysaccharide-binding domain) separated by a less conserved Pro
      Ser-Thr-rich linker region. The mutanase gene was expressed in an E. coli BL21
      (DE3) host, under the transcriptional control of T7 promoter. The purified enzyme
      migrated as a band of about 68 kDa after SDS-polyacrylamide gel electrophoresis,
      which coincided with the predicted size based on the amino acid sequence. Our
      data indicate that this enzyme is highly conserved in Trichoderma and can be
      produced in active form in such heterologous expression system.

PMID- 22390064
TI  - Multiple-locus variable number of tandem repeats fingerprinting (MLVF) and
      virulence factor analysis of methicillin resistant Staphylococcus aureus SCCmec
      type III.
AB  - Methicillin resistant Staphylococcus aureus (MRSA), particularly strains with
      type III staphylococcal cassette chromosome mec (SCCmec), represent a serious
      human pathogen in Tehran, Iran. The disease-causing capability depends on their
      ability to produce a wide variety of virulent factors. The prevalence of exotoxin
      genes and multiple-locus variable number of tandem repeats fingerprinting (MLVF)
      profile among MRSA isolates, from patients in Tehran, was evaluated by PCR and
      Multiplex-PCR. The MLVF typing of 144 MRSA isolates with type III SCCmec produced
      5 different MLVF types. Generally, 97.2% (140/144) of all the isolates were
      positive for at least one of the tested exotoxin genes. The most prevalent genes
      were hld, found in 87.5% (126/144) of the isolates followed by lukE-lukD and hla
      found in 72.9% (105/144) and 70.1% (101/144) of the isolates, respectively. The
      tst gene, belonging to MLVF types I, IV and V, was found among three of the
      isolates from blood and wound samples. The sea gene was detected in 58.3%
      (84/144) of the isolates and the sed and see genes were found in one isolate with
      MLVF type V. The coexistence of genes was observed in the 87.5% (126/144) of the
      isolates. The rate of coexistence of hld with lukE-lukD, hla with lukE-lukD and
      sea with lukE-lukD were 66.7% (96/144), 44.4% (64/144) and 44.4% (64/144),
      respectively. The present study demonstrated that MRSA strains with type III
      SCCmec show different MLVF patterns and exotoxin profiles.

PMID- 22390065
TI  - Antibiotic sensitivity and sequence amplification patterns of genes in multidrug
      resistant enterobacteria isolates from processed foods in some West African
      countries.
AB  - Diarrhoea, dysentery and other diseases due to other enteric bacteria have
      reportedly been found to resist chemotherapeutic treatment in some West African
      communities with fatal consequences in some cases. This study was carried out to
      determine multidrug resistance patterns of Enterobacteria isolates from processed
      ready-to-eat foods. Indigenously processed food samples of different types were
      collected from two Francophone and two Anglophone countries in the West African
      sub-region during the wet and dry seasons of a sampling period of two years.
      Enterobacteria were isolated from the samples using standard techniques.
      Amplification of chromosomal DNA of the isolates using the Polymerase Chain
      Reaction was carried out. The results obtained were subjected to statistical
      analyses. All isolates showed resistance to cefuroxime (90.7%), nitrofurantoin
      (90.6%), augmentin (86.1%) and ampicillin (51.2%) while all were sensitive to
      gentamycin and ciprofloxacin. There was amplification indicating the presence of
      invA gene at a position of 240 bp. There was no amplification at all for the spvC
      gene in any of the isolates tested. Multidrug resistant enteric bacteria in these
      foods containing the invA gene could lead to infections with uncontrolled
      antibiotic use. The presence of enteric bacteria in the foods analyzed which
      provide undeniable evidence of the poor microbiological quality of these foods
      could form the basis of a useful databank in formulation of food-borne disease
      control and prevention strategies.

PMID- 22390066
TI  - Maize plants infestation by Fusarium spp. and deoxynivalenol in genetically
      modified corn hybrid and traditional maize cultivars.
AB  - The objective of the performed investigations was to isolate pathogenic fungi
      from contaminated maize cobs, to assess the appearance of maize cob fusariosis
      and to determine grain contamination with deoxynivalenol in the cultivation of
      genetically modified maize containing a gene resistance against European corn
      borer (Ostrinia nubilalis Hbn) as well as selected non-modified cultivars. The
      plant material comprised the following genetically modified maize cultivar: DKC
      3421 YG (MON 810) and non-modified cultivars obtained from Smolice Plant Breeding
      Ltd., IHAR Group: Junak (FAO 210-220), Prosna (FAO 220), SMH (FAO 230), Baca (FAO
      220). Prior to harvesting, the occurrence of maize cob fusariosis was determined
      in the 89 (BBCH) developmental ripening stage. Microbiological assessment was
      carried out on grains selected from cobs characterized by various pathological
      symptoms. In 2008, a total of 133 isolates was obtained from the examined samples
      of infected maize plants, of which 51 isolates were species-identified, while in
      2009, the total of 123 isolates were determined, of which 63 were species
      identified. In both experimental years, the majority of isolates contained fungi
      from the Fusarium genus. The performed analysis of mean levels of cob
      contamination by fusarioses revealed that DKC 3421 YG (MON 810) and SMH (FAO 230)
      cultivars showed the smallest levels of contamination as well as the lowest
      percent of cob contamination per plant, while Junak (FAO 210-220) and Baca (FAO
      220) cultivars were characterized by the highest degree of contamination. The
      lowest deoxynivalenol concentrations were determined in years 2008 and 2009 in
      the case of the DKC 3421 YG (MON 810) cultivar, whereas Prosna (FAO 220) cultivar
      was characterized by the highest deoxynivalenol concentration.

PMID- 22390067
TI  - Use of potato extract broth for culturing root-nodule bacteria.
AB  - Liquid media containing potato extract and 1% of glucose or sucrose were used to
      culture root-nodule bacteria (rhizobia) in shaken Erlenmeyer flasks. For
      comparison, these bacteria were also cultured in yeast extract-mannitol broth
      (YEMB) as a standard medium. Proliferation of rhizobia was monitored by measuring
      optical densities (OD550) of the cultures and by plate counting of the viable
      cells (c.f.u) of the bacteria. In general, multiplication of the rhizobia in
      potato extract-glucose broth (PEGB) and potato extract-sucrose broth (PESB) was
      markedly faster, as indicated by higher values of OD550, than in YEMB. The
      numbers of R. leguminosarum by. vicae GGL and S. meliloti 330 in PEGB and PEGB
      were high and ranged from 1.2 x 10(10) to 4.9 x 10(10) mL(-1) after 48 h of
      incubation at 28 degrees C. B. japonicum B3S culture in PEGB contained 6.4 x
      10(9) c.f.u. ml(-1) after 72 h of incubation. PEGB and YEMB cultures of the
      rhizobia were similar with respect to their beneficial effects on nodulation of
      the host-plants of these bacteria.

PMID- 22390068
TI  - Changes in gut microbiota in children with atopic dermatitis administered the
      bacteria Lactobacillus casei DN--114001.
AB  - Gut microbiota was analyzed in children, aged 6-18 months and suffering from
      atopic dermatitis before and after 3 month supplementation of their diet with
      Lactobacillus casei DN--114001 in a dose of 109 cells daily. On completion of
      this period the total number of fecal Lactobacillus sp. cells decreased from 7.86
      Log10 CFU/g to 6.40 Log10 CFU/g. After the next 5 months (without dietary
      supplementation with the probiotic bacteria) the level of Lactobacillus sp. cells
      was maintained at the latter value. During the dietary supplementation with the
      probiotic strain, the level of Bifidobacterium cells was maintained at 6.15-6.89
      Log10 CFU/g while after 5 months it decreased to 5.57 Log10 CFU/g. The population
      of Clostridium sp. was reduced after 3 months of dietary supplementation from
      6.49 to 5.83 Log10 CFU/g and was maintained at the latter level during the next 5
      months. The dietary supplementation had no effect on populations of Bacteroides
      sp., Enterococcus sp. and Enterobacteriaceae. Supplementation of children who
      developed atopic dermatitis with the preparation of Lactobacillus casei DN -
      114001 positively affected their gut microbiota in terms of bifidobacteria and
      clostridia populations.

PMID- 22390069
TI  - Comparison of multilocus variable-number tandem-repeat analysis with multilocus
      sequence typing and pulsed-field gel electrophoresis for Enterococcus faecalis.
AB  - Enterococcus faecalis represents recently an important etiological agent of
      health care-associated infections (HAIs) and there is a need for evaluation and
      comparison of typing methods available for this microorganism. We tested
      multilocus VNTR (variable-number tandem repeats) analysis (MLVA) on a well
      characterized collection of 153 clinical isolates of E. faecalis, corresponding
      to 52 multilocus sequence types and 67 pulsed-field gel electrophoresis (PFGE)
      profiles. MLVA showed high discriminatory power, discerning 111 different types
      (diversity index equal 98.9%). The concordance MLVA/MLST and MLVA/PFGE was 0.95
      and 0.74, respectively. High discriminatory power of MLVA indicates its utility
      for local epidemiology such as outbreak investigation, and for differentiation of
      clones defined by other methods.

PMID- 22390070
TI  - Tick-borne infections as a cause of heart transplantation.
AB  - Many bacterial species can be a cause of various heart diseases, such as:
      Borrelia burgdorferi sensu lato, Coxiella burnetii and Bartonella spp. The aim of
      the present studies was to establish if any tick-borne infections can contribute
      to serious heart disorders resulting in the need for heart transplantation.
      Myocardium, aortic and mitral valve samples from hearts removed from patients
      undergoing heart transplantation were tested. The presence of Bartonella spp.,
      Borrelia afzeli and C. burnetii bacteria in malfunctioning human hearts has been
      shown. DNA of Bartonella spp., B. burgdorferi and C. burnetii were detected in
      various parts of tested hearts. DNA of B. afzelii and Bartonella spp. were found
      in the aortic valves. DNA of C. burnetii was detected in the myocardium. Mixed
      infections with Bartonella spp. and C. burnetii were also observed. Obtained
      results indicate that diagnosis of Bartonella spp., B. burgdorferi C. burnetii
      and Rickettsia spp. infections should be considered in cases of infectious
      endocarditis with negative blood cultures.

PMID- 22390071
TI  - Influence of subinhibitory concentrations of cefotaxime, imipenem and
      ciprofloxacin on adhesion of Escherichia coli strains to polystyrene.
AB  - The present study investigated the ability of sub MICs of cefotaxime, imipenem
      and ciprofloxacin to interfere with adhesion of E. coli strains to polystyrene
      (selected polymer used in studies on microorganisms' adhesion). It was observed
      that cefotaxime and imipenem at 1/2 and 1/4 MICs decreased the adherence of E.
      coli strains to polystyrene significantly. 1/2, 1/4 and 1/8 MICs of ciprofloxacin
      generally decreased the adhesive properties of E. coli strains, but two E. coli
      strains showed a noticeable enhancement of adhesion after incubation at sub MICs
      of this antibiotic.

PMID- 22390072
TI  - [Peptidergic modulation of the hippocampus synaptic activity].
AB  - Effects of two newly synthesized nootropic and anxiolytic dipeptides: Noopept and
      Selank on inhibitory synaptic transmission in hippocampal CA1 pyramidal cells
      were investigated using patch-clamp technique in whole-cell configuration. Bath
      application of Noopept (1 microM) or Selank (2 microM) significantly increased
      the frequency of spike-dependent spontaneous m1PSCs, whereas spike-independent
      mlPSCs remained unchanged. It was suggested that both peptides mediated their
      effect sue to activation of inhibitory interneurons terminating on CA1 pyramidal
      cells. Results of current clamp recording of inhibitory interneurons residing in
      stratum radiatum confirmed this suggestion, at least for Noonent.

PMID- 22390073
TI  - [Excitatory action of GABA in ontogenesis].
AB  - GABA (gamma-aminobutyric acid) is the main inhibitory mediator in central nervous
      system. However, at early stages of ontogenesis, GABA has an excitatory effect on
      immature neurons. This review surveys modern concepts of the mechanisms of
      GABAergic excitation and physiological role of excitatory GABA in generation of
      patterns of network activity in developing brain.

PMID- 22390074
TI  - [Prenatal stressed female rats develop stable anxious and depressive state in
      experimental model of post-traumatic stress disorder].
AB  - The effects of immobilization stress from 15th to 19th days of gestation on
      pathological state development in the model of post-traumatic stress disorder in
      adult female offspring were studied. The results showed that prenatally stressed
      female rats as well as control rats demonstrated long-term high anxiety and
      hypersensitive glucocorticoid feedback in the stress-restress model. Enhanced
      depressive-like behaviour was found only in prenatally stressed females. The
      findings were discussed in the light of HPA axis alteration and risk factors for
      development of post-traumatic stress disorder.

PMID- 22390075
TI  - [Neonatal lesions of catecholaminergic system prevents maturation of cholinergic
      innervation of the rat neocortex].
AB  - The influence ofcatecholaminergic system on functioning of the somatosensory and
      cholinergic systems in early ontogenesis in rats was studied. The neonatal
      systemic administration of the neurotoxin 6-hydroxydopamine modifies sensitivity
      of neurons in the somatosensory cortex to peripheral stimulation (stimulation of
      the sciatic nerve). It is shown that in animals with lesions, catecholaminergic
      system reduces the number of the cortical neurons responsive to stimulation of
      ascending cholinergic pathways. The sensitivity of these neurons to acetylcholine
      does not change. The damage in the early ontogeny catecholaminergic mechanisms
      seems to prevent maturation of cholinergic afferents in the neocortex.

PMID- 22390076
TI  - [Effects of chronic nicotine exposure on electrogenic activity of the Na+, K(+)
      ATPase and contractility in the rat diaphragm muscle].
AB  - Rats were chronically treated with nicotine via subcutaneous injections up to a
      dose 6 mg/kg/day during 2-3 weeks. After this period, resting membrane potential
      and action potentials of muscle fibres as well as isometric twitch and tetanic
      (20 s(-1) and 50(-1)) contractions of isolated rat diaphragm were studied. To
      estimate electrogenic contribution of the alpha2 isoform of the Na+, K(+)-ATPase
      ouabain in concentration 1 microM was used. Chronic nicotine exposure induced
      depolarization of resting membrane potential of 2.2 +/- 0.6 mV (p < 0.01). In
      rats chronically exposed to nicotine, electrogenic contribution of the Na+, K(+)
      ATPase alpha2 isoform was twofold lesser than in control animals (3.7 +/- 0.6 mV
      and 6.4 +/- 0.6 mV, respectively, p < 0.01). Chronic nicotine exposure did not
      affect force of twitch and tetanic contractions in response to direct or indirect
      stimulation. A decrease in the twitch contraction time as well as in the rise
      time of tetanic contractions was observed. Fatigue dynamics was unchanged. The
      results suggest that chronic nicotine exposure leads to decrease of the Na+, K(+)
      ATPase alpha2 isoform electrogenic activity, and as a consequence to damage of
      the rat diaphragm muscle electogenesis.

PMID- 22390077
TI  - [Effects of stimulation of nervous fibres upon contractile activity of the
      tracheobronchial lymphatic node capsules' smooth muscles].
AB  - The contractile activity of smooth muscle of tracheobronchial lymph nodes'
      capsules was recorded in vitro. The field electric stimulation (0.5 ms pulses, 55
      V nominal, 4 min trains at frequencies 0.5, 1, 2, 4, 8, 16 and 32 Hz) of strips
      from lymph node produced a frequency-dependent increase in baseline tension and
      frequency of phase contractions. Evoked contractions were significantly (about
      80%) reduced by tetrodotoxin (1 x 10(-6) M). The blockage of M-cholinoreceptors
      with atropine (1 x 10(-6) M) did not affect the field-evoked responses.
      Contractile field-evoked effects were significantly reduced by the phentolamine
      (1 x 10(-7)-1 x 10(-6) M) but not completely. Field-evoked contractions were
      slightly affected by the propranolol (1 x 10(-7)-1 x 10(-6) M). We conclude that
      the contractile activity of bovine tracheobronchial lymph node capsular smooth
      muscle is modulated by excitatory adrenergic nerves.

PMID- 22390078
TI  - [Mechanism of the slow inotropic response of the mouse atrium mediated by the
      beta2-adrenoreceptor].
AB  - The abundant beta2-adrenoceptors (AR) expression was revealed in the mouse atrial
      cardiomyocytes, albeit its function is poorly understood. Recently we revealed
      the slow developing (for 20-40 min) positive inotropic effect in the mouse atrium
      which was induced by the specific agonist of the beta2-adrenoceptors (5 mkM
      fenoterol) and the task of this study involved investigation of the found effect.
      It was shown that stimulation of beta2-AR is enough for rapid triggering of up
      regulation of two signalling pathways that have the opposite influence on the
      contraction force. On one hand, activation of the adenylate cyclase--protein
      kinase A cascade occurs leading to increasing of intracellular Ca2+ concentration
      and amplitude of contraction; on the other hand, activation of the NO-synthase
      and enhance of NO production occurs which prevents the potentiating of the
      contraction force. During the first 15-20 minutes, superposition of these
      activation effects was revealed, which prevented the contraction strength
      increasing. Then the positive inotropic effects occurred due to the decreasing of
      NO production. It was shown that L-type Ca-channels and ryanodine receptors were
      the key targets incorporated in the beta2 adrenoreceptors signalling puzzle.

PMID- 22390079
TI  - [Effects of thermal preconditioning on convulsive activity in rats with
      inheritable form of audiogenic epilepsy].
AB  - Effects of thermal preconditioning universal recognized method of increase in
      concentration of inducible Heat shock protein 70 kDa (Hsp70i) on characteristics
      of convulsive activity in Krushinskii-Molodkina (KM) rats with inheritable
      audiogenic epilepsy were studied. For the first time, it was found that short
      term thermal preconditioning (41 degrees C during 5 minutes) increased duration
      of the latency of audiogenic seizure onset. Thermal preconditioning resulted in
      an increase in concentration of Hsp70i in amygdale, hypothalamus, midbrain; the
      uttermost increase was observed in hippocampus and inferior colliculus: the brain
      areas responsible for initiation of audiogenic seizures. A coincidence was found
      in the term of increase in concentration of Hsp70i and the latency of seizure
      onset (on day 4 after thermal preconditioning). Results of this research confirm
      the proposition that inducible Hsp70i is capable of taking part in the processes
      of seizure development in rats with inheritable form of audiogenic epilepsy.

PMID- 22390080
TI  - [Age-dependent changes of the autonomic neurons expressing vanilloid TRPV1
      receptors].
AB  - Expression of vanilloid receptors in sympathetic and afferent ganglionic neurons
      was studied in rats of different ages (newborn, 10-day old, 20-day old, 30-day
      old, 60-, 180-day old) using immunohistochemical methods. The results obtained
      indicate that the majority of the afferent neurons in the nodose ganglion of
      vagus nerve (GNVN) and in the spinal ganglia (SG) were TRPV1-positive from birth
      onwards. The percentage of neurons containing TRPVT receptors in SG slightly
      increased with age up to 30 days postnatally. In the GNVN, the percentage of
      TRPV1-positive neurons was higher in comparison with the SG in all age groups.
      The vast majority of the sympathetic neurons were TRPV1-positive from birth
      onwards, and the percentage of TRPV1-immunoreactive neurons substantially
      decreased during further development. In 20-day old and older animals, we
      observed only few TRPV1-immunoreactive neurons in sympathetic ganglia. Finally,
      the percentage of neurons containing these types of neurons, become similar to
      adult animals to the end of the first month of life.

PMID- 22390081
TI  - [Peculiarities of hemostasis reactivity under stress load in persons with
      different degree of physical training].
AB  - Healthy young persons with different degrees of physical training have been
      impacted with exposure to a stress (a single physical exercise). It caused
      unidirectional hypercoagulative shifts and activation of anticoagulant and
      fibrinolytic blood systems. It was shown that changes of the untrained
      individuals' haemostatic parameters could be adjusted with adaptogen preliminary
      administration. The adaptogen administration in trained individuals resulted in
      disadaptive shifts in the haemostatic system. These contradictory changes
      indicate different levels of subject's adaptive potential.

PMID- 22390082
TI  - [Thyroid effect on brain activity in adolescents during heart rhythm biofeedback
      session].
AB  - Types of neurophysiologic and thyroid condition in 15-17-year old adolescents
      were studied for the purpose of heart rhythm biofeedback session effect by heart
      rhythm variability parameters. Changes of heart rhythm vegetative regulation
      activity modulate functional capacities of central vegetative regulation
      structures. The biofeedback training with heart rhythm variability parameters
      increases brain bioelectrical activity in different frequency ranges. The thyroid
      system modulates functional activity of vegetative regulation central structures
      uppermost at sympathotonic and thyreotropin increasing leads to increase of
      rhythm maker structure reactivity in brain.

PMID- 22390083
TI  - [Longitudinal oxygen gradients in cerebra micro vessels in acute anaemia in
      rats].
AB  - Using a fine-tip oxygen microelectrodes the longitudinal gradients of oxygen
      tension (pO2) have been studied in small arterioles (with lumen diameter in
      control of 5 +/- 20 microm) and in capillaries of the rat brain cortex during
      stepwise decrease of the blood haemoglobin concentration [Hb] from control [Hb]-
      14.4 +/- 0.3 g/dl to 10.1 +/- 0.2 g/dl (step 1), 7.0 +/- 0.2 g/dl (step 2) and
      3.7 +/- 0.2 g/dl (step 3). All data are presented as "mean +/- standard error".
      Oxygen tension was measured in arteriolar segments in two locations distanced
      deltaL = 265 +/- 34 microm, n = 30. Mean diameter of studied arterioles was 10.7
      +/- 0.5 microm, n = 71. Length of studied capillary segments was about deltaL =
      201 +/- 45 Mm, n = 18. The measured longitudinal pO2 gradient (deltapO2/deltaL)
      in arterioles amounted 0.03 +/- 0.01 mmHg/microm, n = 15 in control; 0.06 +/-
      0.01 mmHg/microm, n = 16 (step 1); 0.07 +/- +/- 0.01 mmHg/microm, n = 14 (step
      2); 0.1 +/- 0.01 mmHg/microm, n = 30 (step 3). In the capillaries, the
      deltapO2/deltaL amounted to: 0.07 +/- 0.01 mmHg/microm, n = 17 (control); 0.09 +/
      0.02 mmHg/microm, n = 16 (step 1); 0.08 +/- 0.01 mmHg/microm, n = 15 (step 2);
      0.1 +/- 0.02 mmHg/microm, n = 18 (step 3). An over threefold decrease in the
      system blood oxygen capacity did not result in significant changes (p > 0.05) of
      the deltapO2/deltaL in capillaries that might result in relatively homogeneous
      oxygen flux from blood to tissue in acute anaemia. The longitudinal gradients of
      blood O2 saturation (deltaSO2/deltaL) in studied arterioles and capillaries were
      obtained using oxygen dissociation curve (ODC) of haemoglobin in the system
      blood. The gradients deltaSO2/deltaL in capillaries was shown to be threefold
      higher than the corresponding gradients in arterioles. The data show that
      anatomic capillaries are the main source of oxygen to brain tissue as in control
      and in hypoxic conditions. Sufficient oxygen delivery to brain tissue in acute
      anaemia is maintained by compensatory mechanisms of cardiovascular and
      respiratory systems. The data presented are the first measurements of the
      longitudinal pO, gradients in capillaries and minute cortical arterioles at acute
      anaemia.

PMID- 22390084
TI  - [Association of heart rate variability and frontal cortex activation].
AB  - Literature data and results of our own research suggest that amplitude of
      periodic modulations of heart rate may be related to the cerebral cortex
      activity. Verification of this assumption was accomplished by searching for
      correlation between the heart rate periodogram (as a measure of amplitude of
      periodic modulations of heart rate at different frequencies), and
      electroencephalographic evaluation of the level of different cortical areas
      activation. Positive association between levels of activation of the frontal
      cortex and amplitude of heart rate modulation with the period of 3 modulations
      per heart rate interval was discovered.

PMID- 22390085
TI  - [Perioperative management of radical prostatectomy: a nationwide survey in
      Japan].
AB  - PURPOSE: Recently, various types of radical surgery have been performed in Japan.
      To elucidate the surgical consequences, morbidity and mortality, and
      perioperative care, we conducted a nationwide survey. MATERIALS AND METHODS:
      Assisted by the Japanese Society of Endourology, perioperative data from 156
      hospitals participating in this survey in 2007 were analyzed. Using a spreadsheet
      database, data were collected from each institution. RESULTS: Open radical
      prostatectomy was performed in 3,138 patients at 143 hospitals, minimum incision
      endourological radical prostatectomy in 361 at 15 hospitals, laparoscopic radical
      prostatectomy via transperitoneal approach in 143 at 11 hospitals and
      laparoscopic radical prostatectomy via extraperitoneal approach in 337 at 13
      hospitals. For open and minimum incision endourological radical prostatectomy,
      the surgical duration was shorter but the bleeding volume was greater than that
      in laparoscopic radical prostatectomy via both approaches. As a whole,
      perioperatvie mortality rate was 0.05% and morbidity rate was 23.4%. Rectal
      injury was similarly infrequent among the four types of surgery. Superficial
      surgical site infection was most frequent in open radical prostatectomy.
      Perioperative management significantly varied among the four types of surgery. In
      laparoscopic radical prostatectomy via extraperitoneal approach, urethral
      catheter was removed earlier but acute urinary retention frequently occurred.
      CONCLUSIONS: In Japan, open radical prostatectomy was the most frequently
      performed surgery for prostate cancer. Surgical volume per hospital was small,
      however, mortality was low and morbidity was acceptable. Comparisons of
      complications and outcomes among the types of currently performed surgery should
      be useful to promote standardization of the perioperative care.

PMID- 22390086
TI  - [Case of renal parenchymal malakoplakia presenting as sepsis and treated with
      nephrectomy].
AB  - Malakoplakia is a rare chronic inflammatory condition characterized by defective
      macrophage function, most of which involve the genitourinary tract, and renal
      parenchymal involvement is uncommon. We present a case of malakoplakia affecting
      renal parenchyma. A 46-year-old woman with pyrexia and jaundice was referred to
      our department. Abdominal enhanced CT scan revealed a left pyelonephritis with
      ureteral stone and bilateral renal abscesses. Despite the insertion of a left
      ureteral stent and administration of antibiotics, the patient showed persistent
      high fever and elevated CRP, and no obvious improvement in clinical and imaging
      data. In view of the limited effectiveness of the conservative treatment in this
      case, we decided to perform left nephrectomy. The diagnosis of malakoplakia was
      made based on the histopathological findings of von Hansemann cells and Michaelis
      Guttmann bodies detected in the nephrectomy specimen. She is clinically healthy
      up to the present (50 months after surgery) with normal clinical indicators and
      CT findings.

PMID- 22390087
TI  - [Case of rectal migratin of mesh after TVM (tension-free vaginal mesh)
      operation].
AB  - A 64-year-old woman presented with recto-cutaneous fistula after tension-free
      vaginal mesh reconstruction using polypropylene mesh for pelvic organ prolapse.
      Eleven months after the operation, an ulcerative lesion with stools smell
      secretion developed in the left hip. Magnetic resonance imaging and colonoscopy
      revealed a migration of the left arm of the mesh and a recto-cutaneous fistula.
      The patient underwent excision of the infected mesh and rectal wall closure
      together with transient colostomy. After 8 months, colonoscopy revealed a new
      migration of the mesh in the rectum, which was also removed. The colostomy was
      closed one year later and rectal erosion has not reccurred since then. The
      possibility of developing a rare but severe mesh-related complication as
      presented here should always be kept in mind.

PMID- 22390088
TI  - [Case of mid-ureteral fibroepithelial polyps in a child].
AB  - A 11-year-old boy showed gross hematuria and left flank pain. Ultrasonography and
      CT revealed left hydroureteronephrosis, and he was referred to us for the further
      evaluation. MRI revealed left hydroureteronephrosis with filling defect at the
      distal end of the dilated ureter suggesting ureteral polyp. Open surgery was
      performed with the diagnosis of mid-ureteral obstruction. In the operative
      findings, multiple stalks of ureteral polyps arose from the entire ureteral wall
      over 5 cm in length at the site of ureteral obstruction. Mid-ureter with polyps
      was completely resected, and end-to-end anastomosis was performed. The
      pathological diagnosis was fibroepithelial polyp of the ureter.

PMID- 22390089
TI  - [Primary retroperitoneal carcinoid tumor associated with multiple endcrine
      neoplasia (men) type 1: a case report].
AB  - We report an extremely rare case of a 69-year-old man having a retroperitoneal
      carcinoid tumor associated with multiple endocrine neoplasia (MEN) type 1. The
      patient whose son and daughter were previously diagnosed with MEN type 1 was
      admitted to the Department of Endocrinology at our hospital for evaluation of
      this disorder. Computed tomography (CT) and ultrasonography revealed a
      parathyroid and retroperitoneal tumor (43 mm x 34 mm). The patient did not
      consent to surgical management of the tumor; however three years later, a follow
      up CT revealed tumor enlargement (55 mm x 50 mm). We were unable to rule out a
      malignancy, and subsequently resected the tumor. A pathological diagnosis of
      retroperitoneal carcinoid was made. No local recurrence or metastasis have been
      observed for 21 months.

PMID- 22390090
TI  - Nursing and guest relations.

PMID- 22390092
TI  - Professional journey to excellence showcase part II.

PMID- 22390091
TI  - When did COPP start and who is COPP?

PMID- 22390093
TI  - Medical Paternalism and Patient Autonomy; the dualism doctors contend with..

PMID- 22390094
TI  - Informed consent: a socio-legal study.
AB  - INTRODUCTION: Informed consent [IC] is a recognized socio-legal obligation for
      the medical profession. The doctrine of IC involves the law, which aims to ensure
      the lawfulness of health assistance and tends to reflect the concept of autonomy
      of the person requiring and requesting medical and/or surgical treatment. Recent
      changes in the health care delivery system and the complex sociological settings,
      in which it is practiced, have resulted in an increase in judicial activity and
      medical negligence lawsuits for physicians. While IC is a well-established
      practice, it often fails to meet its stated purpose. In the common law, the
      standard of medical care to disclose risks has been laid down by the Bolam test-
      a familiar concept to most physicians, but it has been challenged recently in
      many jurisdictions. This paper aims to discuss some important judgments in cases
      of alleged medical negligence so as to familiarize doctors regarding their socio
      legal obligations. We also propose to discuss some factors that influence the
      quality of IC in clinical practice. METHODS: Literature review. RESULTS: The law
      of medical consent has been undergoing changes in recent years. Case law appears
      to be evolving towards a more patient centered standard of disclosure. Patient's
      expectations are higher and they are aware of the power of exercising their
      rights. Failure to obtain IC is one of the common allegations in medical
      malpractice suits. CONCLUSION: The medical professionals need to change their
      mindset and avoid claims of negligence by providing information that is
      "reasonable" in the eyes of the court.

PMID- 22390095
TI  - Screening for intermediate and severe forms of thalassaemia in discarded red
      blood cells: optimization and feasibility.
AB  - Detection and quantification of Hb subtypes of human blood is integral to
      presumptive identification of thalassaemias. It has been used in neonatal
      screening of thalassaemia and Hb variants. The use of discarded red blood cells
      following processing of the cord blood for stem cells provides readily available
      diagnostic material for thalassaemia screening. In this study, we determined the
      range of Hb subtypes in 195 consecutive cord blood samples collected for cord
      blood banking. The 'cord blood samples' analysed were those of the remaining red
      blood cells after the cord blood was processed for stem cell storage.
      Quantification of Hb subtypes by high performance liquid chromatography (HPLC)
      was done on BioRad Variant II Hb testing system. Only 73 (36.5%) of the samples
      could be analyzed neat without dilution. With a 1:300 dilution with wash solution
      the acceptable area as recommended by the manufacturer for reading of a C-gram
      within the 1 to 3 million ranges were achieved in all. Eighteen (9%) 12 showed
      classical Hb Barts (y4) prerun peaks were confirmed by Sebia Hydrasys automated
      Hb gel electrophoresis and quantified by Sebia Capillarys 2 capillary
      electrophoresis. Only 1 (0.5%) was presumptively identified with HbH disease. Due
      to the limited number of samples no beta-thalassaemia major, Hb E beta
      thalassaemia and Hb Barts hydrops fetalis were found. The HPLC assay was possible
      at a cost US$ 5 per sample and a turnover time of 10 samples per hour without
      technical difficulties. This study reports an effective and valuable protocol for
      thalassaemia screening in red blood cells which would otherwise be discarded
      during cord blood processing. Cord blood with severe and intermediate forms of
      thalassaemia can be preselected and not stored.

PMID- 22390096
TI  - Appreciation of learning environment and development of higher-order learning
      skills in a problem-based learning medical curriculum.
AB  - This cross-sectional study determined the appreciation of the learning
      environment and development of higher-order learning skills among students
      attending the Medical Curriculum at the International Medical University,
      Malaysia which provides traditional and e-learning resources with an emphasis on
      problem based learning (PBL) and self-directed learning. Of the 708 participants,
      the majority preferred traditional to e-resources. Students who highly
      appreciated PBL demonstrated a higher appreciation of e-resources. Appreciation
      of PBL is positively and significantly correlated with higher-order learning
      skills, reflecting the inculcation of self-directed learning traits. Implementers
      must be sensitive to the progress of learners adapting to the higher education
      environment and innovations, and to address limitations as relevant.

PMID- 22390097
TI  - Human respiratory epithelial cells from nasal turbinate expressed stem cell genes
      even after serial passaging.
AB  - Current development in the field of tissue engineering led to the idea of
      repairing and regenerating the respiratory airway through in vitro reconstruction
      using autologous respiratory epithelial (RE). To ensure the capability of
      proliferation, the stem cell property of RE cells from the nasal turbinate should
      be evaluated. Respiratory epithelial cells from six human nasal turbinates were
      harvested and cultured in vitro. The gene expression of FZD-9 and BST-1 were
      expressed in passage 2 (P2) and passage 4 (P4). The levels of expression were not
      significant between both passages. The RE cells exhibit the stem cell properties,
      which remains even after serial passaging.

PMID- 22390098
TI  - Endonasal endoscopic transsphenoidal pituitary surgery for pituitary adenoma: a
      retrospective analysis of surgical outcome.
AB  - The purpose of this retrospective joint rhino-neurosurgical study from January
      1998 until September 2009 is to document the demographic data, clinical
      presentations, radiological findings, approaches and incidence of residual
      tumour. Forty-seven patients with pituitary adenoma underwent trans-sphenoidal
      hypophysectomy of which 25 patients with complete medical and radiological data
      were included in the study. The medical and radiological data were analyzed.
      There were 12 males and 13 females with age ranging from 17 to 76 years old (mean
      49.2). Fourteen of the patients were Chinese, eight Malays and three Indians.
      Twelve of the patients had functioning tumour of which five each presented with
      acromegaly and Cushing disease respectively and two with amenorrhoea. The rest of
      13 patients had non functioning tumour presenting with visual disturbances.
      Sixteen of the patients had pituitary macroadenomas and the rest 9 microadenomas.
      Eighteen patients had undergone transcollumellar trans-sphenoidal hypophysectomy
      and the rest 7 patients had undergone transnasal transsphenoidal hypophysectomy.
      About 68.8% of pituitary macroadenomas had residual tumour, compared to only
      22.2% of patient with pituitary microadenomas. Radiologically, about 45.5% of
      residual macroadenoma had suprasellar extension and the majority had spread to
      suprasellar cistern and carvenous sinus (54.5%). About 16.6% of patients had
      undergone post operative radiotherapy. In conclusion, this study showed that
      patient with pituitary macroadenomas had higher incidence of residual tumour
      compared to pituitary microadenomas.

PMID- 22390099
TI  - The effects of fasting during Ramadan on glycemic excursions detected by
      continuous glucose monitoring system (CGMS) in patients with type 2 diabetes.
AB  - OBJECTIVE: Safety of fasting in Ramadan for diabetic patients is not clearly
      known. The aim of this study was to determine the effects of fasting on glycemic
      excursions by continuous glucose monitoring system (CGMS). MATERIALS AND METHODS:
      This pilot, observational study conducted in the Endocrine Research Center,
      Mashhad University of Medical Sciences, Mashhad, IRAN, in Ramadan 2008. Seventeen
      well controlled patients with diabetes type 2 who were taking oral agents
      underwent 72 hour monitoring of glycemic excursions by CGMS one month before
      Ramadan and during Ramadan. The extent and duration of hyperglycemic and
      hypoglycemic events were evaluated and compared. RESULTS: A significant reduction
      in hyperglycemic events was observed during Ramadan. The extent and duration of
      hypoglycemic events was not significantly different between two states (Ramadan
      and before). A significant increase in number of hypoglycemic events in Ramadan
      was found in patients who take sulfonylurea compared with those who take only
      metformin. CONCLUSION: Fasting in Ramadan can be safe for well controlled
      patients with type 2 diabetes.

PMID- 22390100
TI  - Quality of life after haematopoietic stem cell transplantation in a multiracial
      population.
AB  - Haematopoietic stem cell transplantation (HSCT) was started in Malaysia since
      1993 and it has improved the survival of patients with otherwise fatal
      haematological diseases. This study was initiated because quality of life of
      these survivors is an important tool in assessing the outcome of this treatment
      modality. The secondary objective was to identify factors that influenced their
      quality of life. The European Organization of Research and Treatment of Cancer
      Quality of Life Questionnaire (EORTC-30) was used to assess the quality of life
      of eligible patients. A total of 62 patents were recruited. The mean global
      health score (QoL) was 71.2. The major symptoms faced by our patients were
      fatigue, financial difficulty and appetite loss. Appetite loss was an independent
      adverse factor for lower QoL.

PMID- 22390101
TI  - A case control study in factors that affect mammogram compliance.

PMID- 22390102
TI  - Sensitivity and specificity of waist circumference as a single screening tool for
      identification of overweight and obesity among Malaysian adults.
AB  - Generalised obesity and central obesity are risk factors for Type II diabetes
      mellitus and cardiovascular diseases. Waist circumference (WC) has been suggested
      as a single screening tool for identification of overweight or obese subjects in
      lieu of the body mass index (BMI) for weight management in public health program.
      Currently, the recommended waist circumference cut-off points of > or = 94cm for
      men and > or =80cm for women (waist action level 1) and > or = 102cm for men and
      > or = 88cm for women (waist action level 2) used for identification of
      overweight and obesity are based on studies in Caucasian populations. The
      objective of this study was to assess the sensitivity and specificity of the
      recommended waist action levels, and to determine optimal WC cut-off points for
      identification of overweight or obesity with central fat distribution based on
      BMI for Malaysian adults. Data from 32,773 subjects (14,982 men and 17,791 women)
      aged 18 and above who participated in the Third National Health Morbidity Survey
      in 2006 were analysed. Sensitivity and specificity of WC at waist action level 1
      were 48.3% and 97.5% for men; and 84.2% and 80.6% for women when compared to the
      cut-off points based on BMI > or = 25kg/m2. At waist action level 2, sensitivity
      and specificity were 52.4% and 98.0% for men, and 79.2% and 85.4% for women when
      compared with the cut-off points based on BMI (> or = 30 kg/m2). Receiver
      operating characteristic analyses showed that the appropriatescreening cut-off
      points for WC to identify subjects with overweight (> or = 25kg/m2) was 86.0cm
      (sensitivity=83.6%, specificity=82.5%) for men, and 79.1cm (sensitivity=85.0%,
      specificity=79.5%) for women. Waist circumference cut-off points to identify
      obese subjects (BMI > or = 30 kg/m2) was 93.2cm (sensitivity=86.5%,
      specificity=85.7%) for men and 85.2cm (sensitivity=77.9%, specificity=78.0%) for
      women. Our findings demonstrated that the current recommended waist circumference
      cut-off points have low sensitivity for identification of overweight and obesity
      in men. We suggest that these newly identified cut-off points be considered.

PMID- 22390103
TI  - Knowledge and attitude of women regarding the human papillomavirus (HPV)
      infection, its relationship to cervical cancer and prevention methods.
AB  - This study aimed to determine knowledge and attitude of women to HPV and its
      association with cervical cancer and prevention methods. In a cross-sectional
      study, 500 women, aged between 20 and 50 presenting to local health centers in
      Tehran, were asked about demographic factors and questioned about cervical
      cancer, HPV, and prevention methods. Responses were tabulated and summarized.
      Although knowledge of HPV, its relation to cervical cancer and prevention methods
      among Iranian women is not enough, their attitude towards education in this
      regards is extremely high. The results reflect the need of advertising and
      educational programs for public about HPV prevention methods, to reduce the
      prevalence of this infection and its severe consequences.

PMID- 22390104
TI  - Daycare tonsillectomy: a safe outpatient procedure. Hospital Sultanah Bahiyah,
      Alor Setar Malaysia experience.
AB  - OBJECTIVE: We present our experience with daycare tonsillectomy and evaluate
      patient satisfaction and the post operative complication rate. METHODS: A
      prospective audit review of 38 patients from March 2009 till May 2010 was
      conducted in our ambulatory care center. RESULTS: There were 38 patients involved
      in this review. All patients were satisfied with our Ambulatory care services. No
      admission was reported after daycare tonsillectomy. CONCLUSION: Daycare
      tonsillectomy with or without adenoidectomy is safe. It can reduce the waiting
      time and also bed occupancy thus cost effective. Proper selection of patient is
      very important.

PMID- 22390105
TI  - Final height in growth-hormone-treated children with idiopathic growth hormone
      deficiency: the Malaysian experience.

PMID- 22390106
TI  - Case series of foreign body aspiration in Paediatric Institute, Hospital Kuala
      Lumpur.
AB  - A retrospective case series was conducted to determine the clinical
      characteristics and bronchoscopy findings of children with foreign body
      aspiration in Paediatric Institute, Hospital Kuala Lumpur. Ten boys and two girls
      were included (range 2-177 months; median 26 months old). They commonly presented
      with cough (12/100%) and difficulty in breathing (9/75%). All patients had
      unilateral auscultatory findings and the commonest radiographic findings were
      unilateral hyperinflation (7/58.3%). The majority of foreign bodies removed was
      organic (8/66.6%) and more frequently found in the left bronchial tree (7/58.3%).
      Major complications were pneumonia (11/91.6%) and airway oedema (11/ 91.6%).
      Eight patients had delayed diagnosis due to parents unawareness (6/50%) and
      missed diagnosis (2/16.7%).

PMID- 22390107
TI  - Children with learning disabilities in the paediatric clinic, Hospital Tuanku
      Ja'afar Seremban: an overview.
AB  - The aim of the study was to document the prevalence of learning disability among
      the children attending the Paediatric Clinic in Hospital Tuanku Ja'afar Seremban.
      The demographic distribution of these patients; the age of detection of the
      problem; the associated medical conditions and types of intervention received by
      these patients were documented. Patients who were between the ages of five to
      twelve years were included in the study. Learning disability was divided into
      three categories: speech and articulation problems, academic skills disorder and
      other categories which included developmental delay. Children with cerebral palsy
      were excluded from the study. Out of 1320 patients screened, 355 were found to
      have learning disorders. Majority were Malays, with the male to female ratio of
      1.9:1. Most of the patients stayed in Seremban. The learning problem was most
      commonly detected at the age of 4 years and below. The commonest type of learning
      disorder was developmental delay, followed by academic skills disorder, speech
      and academic skills problems and speech disorders. Problems that were detected
      early were speech problems and developmental delay. Majority of the children had
      associated medical conditions. Most of the patients received some form of
      intervention but 11.3% did not attend any intervention program at all. A strategy
      should be formulated and implemented to help this group of children.

PMID- 22390108
TI  - Profiles of men-who-have-sex-with-men seeking anonymous voluntary HIV counseling
      and testing at a community-based centre in Malaysia.
AB  - Community-based HIV voluntary counseling and testing (VCT) services is an
      effective alternative for mapping the local demographics of at-risk populations
      for HIV as well as provide an acceptable and reliable means of early detection of
      HIV. We describe the profiles of men-who-have-sex-with-men (MSM) who sought VCT
      services in a community based centre in Kuala Lumpur.

PMID- 22390109
TI  - Spinal cord compression following traditional confinement massage.
AB  - We describe a case of tetraparesis in a 33-year-old woman following neck
      manipulation performed by a traditional confinement mid-wife. An MRI of the
      cervical spine revealed a fracture of the second cervical vertebra with atlanto
      axial subluxation that resulted in cord compression.

PMID- 22390110
TI  - Tay-Sach disease with "cherry-red spot"--first reported case in Malaysia.
AB  - We present a rare case of Tay-Sachs disease with retinal 'cherry-red spots' in a
      19-month-old Malay child. Molecular genetic studies confirmed the diagnosis. The
      case highlights that 'cherry-red spot' is a useful clinical clue in Tay-Sachs
      disease and several other lysosomal storage disorders. It serves as an ideal
      illustration of the eye as a window to inborn error of metabolism.

PMID- 22390111
TI  - Atrial flutter and pericarditis--a rare complication of right lobe amoebic liver
      abscess.
AB  - A 38 year old gentleman presented with fever and right hypochondrial pain. On
      further evaluation he was detected to have an amoebic liver abscess (ALA) in the
      right lobe of the liver. The abscess yielded anchovy sauce pus on percutaneous
      drainage. Following the percutaneous drainage the patient developed tachycardia.
      Electrocardiogram revealed atrial flutter with rapid ventricular rate and ST
      elevation in all leads suggestive of pericarditis. The atrial flutter was
      reverted to sinus rhythm by cardioversion. The patient then had an uncomplicated
      convalescence. Amoebic pericarditis, though rare, is a serious complication of
      amoebic liver abscess. Pericardial complications are usually seen with left lobe
      liver abscess due to its proximity. Both pericarditis and cardiac arrhythmias due
      to amoebic liver abscess especially from right lobe are very rare.

PMID- 22390112
TI  - An atypical case of retropharyngeal abscess with long blind tract treated with
      Ryle's tube drainage.
AB  - A 10 year-old Iban girl presented with severe odynophagia for 4 days and
      subcutaneous emphysema. Clinically, her neck was tender with crepitus. Lateral
      neck radiograph showed multiple linear radiolucent shadows at retropharyngeal
      space. Flexible nasopharyngolaryngoscope revealed a tunnel behind upper
      oesophagus with slough and there was pooling of saliva at pyriform sinus. Feeding
      via nasogastric tube was started and empirical treatment for fungal and bacterial
      infection was commenced. Subsequent computed tomography of neck and thorax showed
      a 15-long blind tract at subglottic region posterior to oesophagus (prevertebral
      region), extending to superior mediastinum just before carina at T3/T4 level,
      represent abscess. Hourly suctioning of the remaining abscess in the blind tract
      with 10ml-syringe was done.

PMID- 22390113
TI  - Bilateral adrenal histoplasmosis: endoscopic ultrasound-guided fine needle
      aspiration as a method of diagnosis and assessment.
AB  - We report a case of a healthy 78-year-old indonesian man who presented with
      chronic weight loss, poor appetite and lethargy. CT abdomen showed bilateral
      adrenal masses. EUS-guided FNA was performed on the left adrenal gland.
      Histopathology report was Histoplasma Capsulatum. He recovered well with
      antifungal treatment without any complication. In this case, we found that the
      role of EUS -guided FNA was not only limited to diagnosis but also helped in the
      prognosis of the disease since the method was able to assess the general anatomy
      of the adrenal gland better than other imaging modalities due to its close
      proximity and direct visualization.

PMID- 22390114
TI  - More than meets the smile: facial muscle expression in children with Ochoa
      syndrome.
AB  - The Ochoa syndrome is the association of a non-neurogenic neurogenic bladder with
      abnormal facial muscle expression. Patients are at risk for renal failure due to
      obstructive uropathy. We report a family of three siblings, with an emphasis on
      the abnormalities in facial expression. Careful examination shows an unusual co
      contraction of the orbicularis oculi and orbicularis oris muscles only when full
      facial expressions are exhibited, across a range of emotional or voluntary
      situations. This suggests a peripheral disorder in facial muscle control. Two
      thirds of patients have anal sphincter abnormalities. Aberrant organisation of
      the facial motor and urinary-anal sphincter nuclei may explain these symptoms.

PMID- 22390115
TI  - Acardius amorphus: magnetic resonance imaging (MRI) can be helpful in the
      diagnosis when ultrasound (US) is inconclusive.
AB  - An acardiac twin is rare and the diagnosis is commonly achieved from antenatal
      ultrasound (US) scans. However there have been cases where the appearances of the
      acardiac twin can be confusing and mimics a mass or tumour, for example, a
      teratoma. We experienced a case where the findings were unclear from the
      antenatal ultrasound scans and we had to resort to Magnetic Resonance Imaging
      (MRI), where we finally made the correct diagnosis based on the identification of
      two umbilical cords, supplying the normal fetus and the 'mass' (acardiac twin)
      respectively.

PMID- 22390116
TI  - Internal iliac artery pseudo aneurysm occlusion using amplatzer vascular plug.
AB  - Pseudoaneurysm of the internal iliac artery is a rare occurrence. Our patient
      presented with pain over the lower abdomen which also radiated to the back. An
      Angiogram of the aorta and the iliac arteries showed a pseudoaneurysm of the
      right internal iliac artery which measured about 8 x 8 cm with a proximal branch
      of the internal iliac artery distended. Initial efforts of trying to embolize the
      pseudoaneurysm revealed that there was a connection between the pseudoaneurysm
      and the interanal iliac vein where foam was getting dislodged into the venous
      system. Subsequently, we decided to use a vascular plug which has just been
      recently being introduced. Post procedure there was no more flow into the right
      internal iliac artery pseudoaneurysm.

PMID- 22390117
TI  - It's aneurysmal, it's stenotic, it's tuberculosis.
AB  - Tuberculous vasculitis is a very rare presentation of tuberculosis. So far this
      is the second reported case in the literature. The diagnosis of this disorder is
      based on the clinical presentation as well as blood investigation results. With
      the ever improvement in modern medicine and improvement in endovascular treatment
      of such diseases, the morbidity and mortality of these patients have been
      dramatically reduced with better clinical and survival results. We present a case
      of endovascular stenting of a stenotic subclavian artery with good results.

PMID- 22390118
TI  - Churg-Strauss syndrome presenting with conjunctival and eyelid masses: a case
      report.
AB  - Churg-Strauss syndrome, a small and medium vessel vasculitis, was first described
      by Churg and Strauss in 1951. It is characterised by the presence of asthma,
      prominent tissue and blood eosinophilia, systemic vasculitis, and pulmonary and
      systemic necrotising allergic granulomas. Involvement of the skin, heart and
      gastrointestinal tract is well documented, but ocular presentation is unusual. We
      describe a 40-year-old lady who presented with recurrent upper eyelid swelling
      due to conjunctival lesions. Although she has chronic asthma, Churg-Strauss
      syndrome was never suspected. The diagnosis of Churg-Strauss syndrome was only
      made following histological examination of the conjunctival lesions.

PMID- 22390119
TI  - Tako-Tsubo like syndrome triggered by meperidine.
AB  - We present a case of "inverted Tako-Tsubo" syndrome in a woman sedated with
      meperidine before undergoing a colonscopy. We discuss possible etiology of this
      ventricular dysfunction.

PMID- 22390120
TI  - Thalassaemia screening among students in a secondary school in Ampang, Malaysia.
AB  - Thalassaemia is a common disorder in Malaysia. It is estimated that 4.5% of the
      population are carriers for beta- or alpha- thalassaemias. We set out to screen
      Form 4 students aged between 15 and 16 years old in a national school, for
      thalassaemia in March 2008. Written consent was obtained from 310 students. The
      carrier rate for the common thalassaemia syndromes was 6.8% (2.9% for beta
      thalassaemia, 2.6% for HbE and 1.3% for two-gene deletion for alpha
      thalassaemia). Carriers for beta-thalassaemia and two-gene deletion for alpha
      thalassaemia were more common in the Chinese (4.3% and 1.4% respectively) while
      heterozygous HbE was more common in the Malays (3.8%). The laboratory cost of
      screening one student was RM 45 and the total number of man-hours spent in this
      screening activity was 600. This screening exercise showed that thalassaemia
      carriers are common among the Chinese and Malays and it is feasible to carry out
      a screening programme for secondary school students.

PMID- 22390121
TI  - Globus sensation in throat, the lymphoid and non-lymphoid origin of tongue base
      lesions.

PMID- 22390122
TI  - Critical appraisal of the existing and emerging therapies for smoking cessation.
AB  - Smoking is a major health problem of the society as it causes a wide variety of
      health hazards and produces a strong addictive behavior. Various pharmacological
      and non pharmacological treatments have been tried for smoking cessation from
      time to time. Some of the pharmacological treatments have been able to achieve
      the status of first line and second line therapy for smoking cessation by the US
      Public Health Service Clinical Practice Guideline. Some newer and very promising
      drugs have come up and are in the clinical trials for establishment of their
      efficacy. While some other drugs have been tried from time to time but have
      failed to show any consistent results. Various non pharmacological therapies like
      behavioural therapy are also of utmost importance in this regard. This article
      gives a brief review and critical assessment of the existing and the emerging
      smoking cessation therapies.

PMID- 22390123
TI  - [90th anniversary of the Chair and Department of Forensic Medicine Poznan
      University of Medical Sciences].
AB  - The paper outlines the history of the Chair and Department of Forensic Medicine
      Poznan University of Medical Sciences since it was established until today.
      Changes in the appearance and organization of the seat of the institution were
      discussed briefly. The profiles of all former heads of the Department, their
      contribution to the development and improvement of the institution and formation
      of the new scientific forensic medicine staff were presented. The specification
      and analysis of the scientific staff achievements was performed, especially
      taking into account their scientific publications and scope of the research that
      contributed to the efficient service activities for the prosecution and police,
      as well as society.

PMID- 22390124
TI  - [Penetration depth of missiles fired from a pneumatic weapon with kinetic energy
      below 17 J, in 20% gelatine blocks as correlated with injuries found during
      autopsy of a 9-year-old boy].
AB  - In Poland, according to the Act About Weapons and Ammunition, an air weapon which
      has kinetic energy of the fired projectiles below 17 J does not require
      registration and can be bought even on the Internet. Sport and recreation
      shooting with this weapon basically have to be performed in shooting ranges, but
      can be also carried on outside of shooting ranges, providing "particular caution"
      is exercised. In this study, we presented a case of fatal shooting of a 9-year
      old boy; the weapon was a Chinese pneumatic device weapon with kinetic energy of
      the fired projectiles below 17 J. The aim of this study was to compare autopsy
      findings with penetration depth of missiles fired from this pneumatic weapon in
      20% gelatine blocks. During the experiment, we used a Chinese pneumatic weapon
      with kinetic energy below 17 J, five kinds of lead projectiles with different
      shape and mass and 20% gelatine blocks at the temperature of 10 degrees C, which
      were the model of human soft tissues.

PMID- 22390125
TI  - [Comparison of bite marks and teeth features using 2D and 3D methods].
AB  - The nature of bite marks is complex. They are found at the scene of crime on
      different materials and surfaces - not only on human body and corpse, but also on
      food products and material objects. Human bites on skin are sometimes difficult
      to interpret and to analyze because of the specific character of skin--elastic
      and distortable--and because different areas of human body have different
      surfaces and curvatures. A bite mark left at the scene of crime can be a highly
      helpful way to lead investigators to criminals. The study was performed to
      establish: 1) whether bite marks exhibit variations in the accuracy of
      impressions on different materials, 2) whether it is possible to use the 3D
      method in the process of identifying an individual based on the comparison of
      bite marks revealed at the scene, and 3D scans of dental casts, 3) whether
      application of the 3D method allows for elimination of secondary photographic
      distortion of bite marks. The authors carried out experiments on simulated cases.
      Five volunteers bit various materials with different surfaces. Experimental bite
      marks were collected with emphasis on differentiations of materials.
      Subsequently, dental impressions were taken from five volunteers in order to
      prepare five sets of dental casts (the maxilla and mandible. The biting edges of
      teeth were impressed in wax to create an imprint. The samples of dental casts,
      corresponding wax bite impressions and bite marks from different materials were
      scanned with 2D and 3D scanners and photographs were taken. All of these were
      examined in detail and then compared using different methods (2D and 3D). RESULT:
      1) Bite marks exhibit variations in accuracy of impression on different
      materials. The most legible reproduction of bite marks was seen on cheese. 2) In
      comparison of bite marks, the 3D method and 3D scans of dental casts are highly
      accurate. 3) The 3D method helps to eliminate secondary photographic distortion
      of bite marks.

PMID- 22390126
TI  - [Problems associated with age estimation of underage persons who appear in child
      pornography materials].
AB  - Among opinions issued by the Forensic Medicine Department, Medical Science
      University in Poznan, in the last six years, there are opinions concerning age
      estimation in child pornography materials. The issue subject to research is
      indicating persons under the age of 15 years in pornographic materials, since
      possession of pornographic materials featuring underage persons is considered a
      crime and is subject to article 202 of the Penal Code. The estimation of the age
      of teenagers based on secondary and tertiary sexual characteristics is
      increasingly more difficult and the available data in professional literature
      regarding the standard time of development differ among various authors of such
      studies. In the report, an attempt has been made at determining the agreement
      regarding different characteristics in the data included in the Tanner's scale,
      which has been modified to accommodate the research done on persons registered by
      electronic means. The modified scale, which up to now has been used in research
      of registered subjects in classified public prosecutors' materials, has been
      employed in children seen in a pediatric outpatient department. The goal has been
      a comparison of the outcome of the research to prove its usefulness so that in
      the future, the modified scale could be used as a research tool in estimation of
      age of persons appearing in pornography materials. MATERIAL AND METHOD: medical
      forms of 205 children seen in a pediatric outpatient department, based on the
      scale created by the present authors us and later processed using Excel.

PMID- 22390127
TI  - [Causes of perinatal deaths in children delivered out of hospital in material
      collected by Chair and Department of Forensic Medicine, Medical University of
      Warsaw].
AB  - The study focused on cases of perinatal deaths of infants delivered out of
      hospital. The objective of the investigation was to determine the number of such
      cases in the Warsaw region, focusing in particular on suspected infanticides,
      evaluate the most frequent causes of death of children born out of hospital and
      determine possibilities and limitations of autopsies performed in neonates. The
      material comprised autopsy reports pertaining to 27 forensic perinatal postmortem
      examinations performed at the Chair and Department of Forensic Medicine, Warsaw
      Medical University, Poland, in the years 2001-2008. Determination of cause of
      death was possible in more than half of the cases. The most frequent cause of
      death was prematurity. A congenital malformation was seen in one neonate only.
      The most common factor that hindered determination of cause of death was advanced
      putrefaction, as well as unavailability of the placenta for examinations noted in
      more than 50% of the cases.

PMID- 22390128
TI  - [Y-STR Poland--a database for evaluation of evidence value in forensic genetics].
AB  - The "Y-STR Poland" is a multicenter project, the aim of which is the construction
      of a widely available database of Y chromosome haplotypes determined in the
      Polish population in a range of sixteen loci in AmpFISTR Y-filer system. The
      database will be regularly updated and it will be used in assessment of evidence
      value in forensic genetics. The starting base "Y-STR Poland" contains 1600 Y-STR
      haplotypes and encompasses data collected in Lodz (two independent centers),
      Warsaw and Szczecin regions. The present report contains as an attachment the
      data in an Excel-type file, which serves as a tool in frequency determination of
      a given Y haplotype in the Polish population. The file will be updated on a
      regular basis along with updating the database, and will be freely available from
      www.genetyka-sadowa.pl.

PMID- 22390129
TI  - [Validation and evaluation of a five miniSTRs kit in forensic genetics].
AB  - The newly designed and optimized miniplex contains the following markers:
      D3S3053, D6S474, D9S2157, D20S482 and sex-determining marker - amelogenin. The
      target amplicon lengths for the developed multiplex are 71-135 bp. Amplification
      products were detected in a fluorescence based automated genetic analyzer. A
      minimal DNA sample required to obtain full genetic profiles was 250 pg. The
      usefulness of these miniSTRs in genotyping of severely degraded forensic samples,
      such as stains of blood and semen, saliva on cigarette butts and telogen hair has
      been confirmed in validation studies. The designed pentaplex offers a new
      potential screening tool in cases of old crime scenes, mass disasters, mass
      graves, etc., where DNA degradation, body fragmentation or large numbers of
      victims occur. The use of additional non-CODIS markers may increase typeability
      of severely degraded samples and ensure a higher potential for genetic
      discrimination.

PMID- 22390130
TI  - [Application of Y-SNPs in forensic genetics].
AB  - The study presents the results obtained by LightSNiP method with the use of 2
      SNPs located on Y chromosome. The purpose of this study was examination of the
      mixture of the genetic material in the form of male and female blood in different
      dilutions. The size of available STR-PCR markers is between 100 and 500 bp, which
      can limit the possibility of DNA mixture analysis, where the amount of male DNA
      is relatively low or the genetic material is markedly degraded. Selection of
      appropriate SNPs placed on Y chromosome can provide information that will
      facilitate interpretation of the female and male DNA mixture. The test was
      performed on a Light Cycler 2.0, Roche Diagnostic.

PMID- 22390131
TI  - [Fatal injuries of organs situated in the neck caused by fastened seat belts].
AB  - The authors present the type and extent of injuries inflicted as a result of the
      victims wearing fastened seat belts during frontal impacts of the vehicles. As an
      example of a particular traffic accident, the authors describe a rare case of
      neck injuries resulting from improper fitting of the safety belt to the victim's
      height. The driver of the car that had frontally hit the obstacle was killed on
      the spot, while the female passenger, was taken to hospital in a severe
      condition, where she died several hours later. The direct cause of death of the
      passenger were injuries of the organs situated in the neck, such as rupture
      larynx, epiglottis and the thyroid cartilage, as well as the hyoid bone fracture
      resulting from an impact with a fastened safety belt.

PMID- 22390132
TI  - [Pedestrian dragged under a truck].
AB  - A traffic accident is described, involving a pedestrian who was at first hit and
      subsequently hooked up by his clothing by a suspension element of a low-floor
      truck trailer and dragged along a road for the distance of 3500 m. Autopsy
      demonstrated that the pedestrian died of cerebro-cranial injuries, inflicted
      while he had been hit by the truck. Additionally, the frontal surface of his body
      demonstrated external injuries typical for dragging of the body along the
      roadway. Before being dragged, the pedestrian was hit by the front of the
      vehicle, when he was in a sitting position, or was rising or else was in a
      recumbent position with an elevated head and trunk. Traffic accidents of the type
      were seldom described in the national and foreign literature.

PMID- 22390133
TI  - [DNA studies performed on a mummified body from Forensic Department Museum of
      Poznan University of Medical Sciences].
AB  - The article presents the results of experimental DNA examinations of a mummified
      body, which is kept in the Forensic Department Museum of Poznan University of
      Medical Sciences. The DNA analysis determined the gender of the mummy as male;
      the body was found to belong to the Y-chromosome haplogroups R1b and J2. The age
      of the mummified body was estimated by an anthropological examination as
      approximately 35 years.

PMID- 22390134
TI  - [Problem of exposure to direct danger of death or grave detriment to health of a
      child breast-fed by an alcohol-abusing mother in medico-legal opinions].
AB  - In the last few years, the authors have noted an increasing amount of cases
      submitted for analysis in the Chair and Department of Forensic Medicine, Poznan
      University of Medical Sciences, and addressing alcohol abuse by breast-feeding
      mothers. A question about the exposure to direct danger of death or grave
      detriment to health of a child by a breast-feeding mother under the influence of
      alcohol is posed by prosecution or the court, and the expectation is obtaining
      answers from forensic experts as to whether the situation fulfills the meaning of
      article 160 of the penal code, which would result in the mother bearing criminal
      liability. Difficulties that have arisen during the analysis of such cases have
      prompted the authors to analyze the problem of alcohol abuse by breast-feeding
      mothers in terms of medico-legal opinions.

PMID- 22390135
TI  - Construction of a natural mucin microarray and interrogation for biologically
      relevant glyco-epitopes.
AB  - Mucins are the principal components of mucus, and mucin glycosylation has
      important roles in defense, microbial adhesion, immunomodulation, inflammation,
      and cancer. Mucin expression and glycosylation are dynamic, responding to changes
      in local environment and disease. Potentially hundreds of heterogeneous glycans
      can substitute one mucin molecule, and it is difficult to identify biologically
      accessible glyco-epitopes. Thirty-seven mucins, from the reproductive and
      gastrointestinal (GI) tracts of six species (bovine, ovine, equine, porcine,
      chicken, and deer) and from two human-derived cell lines, were purified.
      Following optimization of mucin printing and construction of a novel mucin
      microarray, the glycoprofiles of the whole mucins on the microarray were compared
      using a panel of lectins and one antibody. Accessible glyco-motifs of GI mucins
      varied according to species and localization of mucin origin, with terminal
      fucose, the sialyl T-antigen, and N-linked oligosaccharides identified as
      potentially important. The occurrence of T- and sialyl T-antigen varied in bovine
      and ovine reproductive tract mucins, and terminal N-acetylgalactosamine (GalNAc)
      and sulfated carbohydrates were detected. This study introduces natural mucin
      microarrays as an effective tool for profiling mucin glyco-epitopes and
      highlights their potential for discovery of biologically important motifs in
      bacterial-host interactions and fertility.

PMID- 22390136
TI  - Preoperative rectal cancer staging with phased-array MR.
AB  - BACKGROUND: We retrospectively reviewed magnetic resonance (MR) images of 96
      patients with diagnosis of rectal cancer to evaluate tumour stage (T stage),
      involvement of mesorectal fascia (MRF), and nodal metastasis (N stage).Our gold
      standard was histopathology. METHODS: All studies were performed with 1.5-T MR
      system (Symphony; Siemens Medical System, Erlangen, Germany) by using a phased
      array coil. Our population was subdivided into two groups: the first one, formed
      by patients at T1-T2-T3, N0, M0 stage, whose underwent MR before surgery; the
      second group included patients at Tx N1 M0 and T3-T4 Nx M0 stage, whose underwent
      preoperative MR before neoadjuvant chemoradiation therapy and again 4-6 wks after
      the end of the treatment for the re-staging of disease.Our gold standard was
      histopathology. RESULTS: MR showed 81% overall agreement with histological
      findings for T and N stage prediction; for T stage, this rate increased up to 95%
      for pts of group I (48/96), while for group II (48/96) it decreased to
      75%.Preoperative MR prediction of histologically involved MRF resulted very
      accurate (sensitivity 100%; specificity 100%) also after chemoradiation
      (sensitivity 100%; specificity 67%). CONCLUSIONS: Phased-array MRI was able to
      clearly estimate the entire mesorectal fat and surrounding pelvic structures
      resulting the ideal technique for local preoperative rectal cancer staging.

PMID- 22390137
TI  - Orthodontic surgery and professional liability: the homozygote twin case.
AB  - A professional liability lawsuit of an orthodontic case is presented through its
      medico-legal assessment. The patient underwent an orthodontic treatment combined
      with several maxillo-facial surgical interventions. Several temporomandibular
      joint complications followed, plus he was unhappy with aesthetic results and
      modifications to his facial features. He wanted to verify from a medico-legal
      point of view the treatment received as he believed something was not done lege
      artis. The result of the orthodontic assessment was that there were no
      indications for such surgical interventions, along with other professional
      negligence: no psychological support given and no indications as to the aesthetic
      results postsurgery. It was decided to carry out an orthodontic assessment also
      on his homozygote twin brother, who was discovered to have the same malocclusion.
      His medico-legal assessment did not substitute the evidence obtained from the
      deceased, but gave added weight to the final technical conclusion.

PMID- 22390139
TI  - Indoles in multicomponent processes (MCPs).

PMID- 22390138
TI  - Feedback regulation by Atf3 in the endothelin-1-responsive transcriptome of
      cardiomyocytes: Egr1 is a principal Atf3 target.
AB  - Endothelin-1 promotes cardiomyocyte hypertrophy by inducing changes in gene
      expression. Immediate early genes including Atf3 (activating transcription factor
      3), Egr1 (early growth response 1) and Ptgs2 (prostaglandin-endoperoxide synthase
      2) are rapidly and transiently up-regulated by endothelin-1 in cardiomyocytes.
      Atf3 regulates the expression of downstream genes and is implicated in negative
      feedback regulation of other immediate early genes. To identify Atf3-regulated
      genes, we knocked down Atf3 expression in cardiomyocytes exposed to endothelin-1
      and used microarrays to interrogate the transcriptomic effects. The expression of
      23 mRNAs (including Egr1 and Ptgs2) was enhanced and the expression of 25 mRNAs
      was inhibited by Atf3 knockdown. Using quantitative PCR, we determined that
      knockdown of Atf3 had little effect on up-regulation of Egr1 mRNA over 30 min,
      but abolished the subsequent decline, causing sustained Egr1 mRNA expression and
      enhanced protein expression. This resulted from direct binding of Atf3 to the
      Egr1 promoter. Mathematical modelling established that Atf3 can suffice to
      suppress Egr1 expression. Given the widespread co-regulation of Atf3 with Egr1,
      we suggest that the Atf3-Egr1 negative feedback loop is of general significance.
      Loss of Atf3 caused abnormal cardiomyocyte growth, presumably resulting from the
      dysregulation of target genes. The results of the present study therefore
      identify Atf3 as a nexus in cardiomyocyte hypertrophy required to facilitate the
      full and proper growth response.

PMID- 22390140
TI  - Illness representations in patients with multimorbid long-term conditions:
      qualitative study.
AB  - Most research on illness representations explores how patients view single
      conditions, but many patients report more than one long-term condition (known as
      multimorbidity). It is not known how multimorbidity impacts on patient illness
      representations. This exploratory qualitative study examined patients'
      representations of multimorbid long-term conditions and sought to assess how
      models of illness representation might need modification in the presence of
      multimorbidity. We explored two major issues: (1) the impact of multimorbidity on
      patient representations of their individual conditions and (2) the representation
      of multimorbidity itself. Twenty eight adults with at least two long-term
      conditions (mean of 4) were interviewed. The presence of multimorbidity impacted
      on patient illness representations in relation to the dimensions of identity,
      perceived cause, coherence and consequences. Representations of multimorbidity
      itself concerned representations of the burden of medication and perceived
      priorities among conditions and synergies and antagonisms between conditions and
      their management. The results have implications for the measurement of
      multimorbidity (through scales such as the Illness Perception Questionnaire) and
      the use of illness representations in the design and delivery of interventions to
      improve health behaviour and outcomes of patients with multiple long-term
      conditions.

PMID- 22390141
TI  - Concise route to 3-arylisoquinoline skeleton by Lewis acid catalyzed C(sp3)-H
      bond functionalization and its application to formal synthesis of (+/-)
      tetrahydropalmatine.
AB  - An expeditious route to furnish an isoquinoline skeleton via hydride shift
      mediated C-H bond functionalization was developed. In this process, an unusual
      [1,5]-H shift without the assistance of the adjacent heteroatom took place to
      produce tetrahydroisoquinoline derivatives in good to excellent chemical yields.
      The formal synthesis of (+/-)-tetrahydropalmatine was achieved by exploiting this
      new transformation.

PMID- 22390142
TI  - Tetrahydrofuran-induced K and Li doping onto poly(furfuryl alcohol)-derived
      activated carbon (PFAC): influence on microstructure and H2 sorption properties.
AB  - We have doped poly(furfuryl alcohol)-derived activated carbon (PFAC) with two
      alkali metals, potassium (K) and lithium (Li), by previously reacting the metals
      with naphthalene in the presence of tetrahydrofuran (THF), followed by
      introducing them to pristine PFAC. The THF molecule causes a minor alteration of
      the microstructure of PFAC as confirmed by Raman spectra, X-ray diffraction, and
      pore textural analysis. Raman spectra and X-ray diffraction indicated a slight
      localized ordering toward the stacking defects of disordered carbon, as in PFAC,
      which can be attributed to the movement of THF molecules within the internal
      planes of graphene sheets. Pore textural analysis confirmed the lowering of the
      specific surface area and pore volume of both K- and Li-doped PFACs (BET SSA,
      1378 m(2)/g (PFAC); 1252 m(2)/g (K-PFAC), 1081 m(2)/g (Li-PFAC)). Volumetric
      hydrogen adsorption measurements at temperatures of 298, 288, 273, and 77 K and
      pressures of up to 1 bar indicated the enhanced adsorption potential imposed by
      the presence of alkali metals, which can be reconfirmed by the elevated heats of
      adsorption of metal-doped PFACs (Li-PFAC, -(10-11) kJ/mol; K-PFAC, -(16-19)
      kJ/mol) compared to that of pristine PFAC (-9.6 kJ/mol).

PMID- 22390143
TI  - Development, reproducibility and validity of the food frequency questionnaire in
      the Poland arm of the Prospective Urban and Rural Epidemiological (PURE) study.
AB  - BACKGROUND: A food frequency questionnaire (FFQ) is the most commonly used method
      in large epidemiological studies. The validation of an FFQ is essential for
      specific populations because foods are culture-dependent. The present study aimed
      to develop an FFQ and evaluate its validity and reproducibility in estimating the
      intake of nutrients in urban and rural areas of Poland. METHODS: Adult
      participants (n = 146) in the Polish arm of the ongoing Prospective Urban and
      Rural Epidemiological (PURE) study completed FFQs on two occasions, as well as
      four 24-h dietary recalls (DRs) during a 12-month period. Correlation
      coefficients (r) and de-attenuated correlation coefficients between dietary
      recalls and both FFQs were calculated for selected macro- and micronutrients.
      Agreement between the two methods was evaluated by classification into quartiles
      and the Bland-Altman method. Reproducibility was assessed by the intra-class
      correlation coefficient (ICC). RESULTS: The final food list contained 134 food
      items. For urban participants, FFQ2 generally underestimated energy, protein and
      fat compared to the FFQ1 and mean of DRs. In rural areas, compared to DRs, both
      FFQs overestimated energy and macronutrients. For both urban and rural settings,
      de-attenuated correlation exceeded 0.4 for almost all nutrients and the exact
      agreement in quartile categorisation was >66%. When assessing repeatability, ICC
      varied from 0.39-0.63 in an urban setting and 0.19-0.45 in a rural setting.
      CONCLUSIONS: This 134-item FFQ has good validity and reproducibility in relation
      to the reference method and can be used to rank individuals based on their macro-
      and micronutrient intake.

PMID- 22390144
TI  - Adult Kawasaki disease: evaluating the fluctuation of circulating lymphocytes
      associated with i.v. immunoglobulin treatment.

PMID- 22390145
TI  - 'In this world nothing can be said to be certain, except death and taxes'
      Benjamin Franklin, 1789.

PMID- 22390146
TI  - The importance of training in anorectal pathology among medical specialities.

PMID- 22390150
TI  - Successful endoscopic needle knife therapy combined with topical doxycycline
      injection of chronic sinus at ileal pouch-anal anastomosis.
AB  - AIM: Chronic presacral sinus at the anastomosis after restorative proctocolectomy
      and ileal pouch-anal anastomosis (IPAA) has been difficult to manage and results
      in a high rate of pouch failure. The aim was to present a novel technique with a
      combining endoscopic doxycycline injection and needle knife therapy for a sinus
      at the ileoanal anastomosis. METHODS: We applied repeat Doppler ultrasound-guided
      endoscopic needle knife therapy to open the orifice of the anastomotic sinus
      followed by topical injection of doxycycline. RESULTS: After six sessions of the
      endoscopic therapy, the refractory sinus was completely healed. CONCLUSION:   The
      Doppler ultrasound guided endoscopy therapy may provide an alternative treatment
      option for the patients with anastomotic sinus.

PMID- 22390151
TI  - Th17 cells induce a distinct graft rejection response that does not require IL
      17A.
AB  - IL-17A-producing helper T (Th17) cells have been implicated in the pathogenesis
      of autoimmune disease, inflammatory bowel disease and graft rejection, however
      the mechanisms by which they cause tissue damage remain ill-defined. We examined
      what damage Th17 cell lines could inflict on allogeneic skin grafts in the
      absence of other adaptive lymphocytes. CD4(+)  Th17 cell lines were generated
      from two TCR transgenic mouse strains, A1(M).RAG1(-/-)  and Marilyn, each
      monospecific for the male antigen Dby. After prolonged in vitro culture in
      polarizing conditions, Th17 lines produced high levels of IL-17A with inherently
      variable levels of interferon gamma (IFNgamma) and these cells were able to
      maintain IL-17A expression following adoptive transfer into lymphopenic mice.
      When transferred into lymphopenic recipients of male skin grafts, Th17 lines
      elicited a damaging reaction within the graft associated with pathological
      findings of epidermal hyperplasia and neutrophil infiltration. Th17 cells could
      be found in the grafted skins and spleens of recipients and maintained their
      polarized phenotype both in vivo and after ex vivo restimulation. Antibody
      mediated neutralization of IL-17A or IFNgamma did not interfere with Th17-induced
      pathology, nor did it prevent neutrophil infiltration. In conclusion, tissue
      damage by Th17 cells does not require IL-17A.

PMID- 22390152
TI  - Predictors of treatment utilisation at cognitive remediation groups for
      schizophrenia: the roles of neuropsychological, psychological and clinical
      variables.
AB  - The present study highlights the importance of carefully assessing
      neuropsychological functioning at the outset of cognitive remediation (CR)
      treatment. The effects of neuropsychological, psychological, and clinical
      variables on treatment utilisation (TU) in CR groups for individuals with
      schizophrenia were examined. Data included neuropsychological and psychosocial
      assessments conducted with 39 adult clients enrolled in CR as part of their
      ongoing outpatient therapy. TU was calculated using the percentage of sessions
      attended over a three-month period. Better global neuropsychological functioning
      (r = .46, p = .007), attention/working memory (r = .39, p = .03), and processing
      speed (r = .44, p = .01) were each associated with greater TU. Trend-level
      associations with TU were observed with executive functioning (r = .33, p = .06)
      and verbal learning (r = .23; p = .07). Higher rates of self-reported cognitive
      complaints were associated with lower TU (r = -.45, p = .01). Hierarchical
      regression analyses revealed that both objective and subjective indicators of
      neuropsychological functioning independently contributed to the prediction of TU.
      This information can serve to help providers develop empirically informed
      strategies to support their clients' CR treatment utilisation. The implications
      from these findings can be used as a way to provide ongoing guidance for service
      provision and can aid in improving CR treatment utilisation, and thus treatment
      effectiveness, in clinical settings.

PMID- 22390154
TI  - Direct amination of gamma-halo-beta-ketoesters with anilines.
AB  - The direct amination of alpha-haloacetoacetates with anilines is described.
      Compared to existing methods, this simple protocol provides an attractive
      strategy to prepare diverse gamma-anilino-beta-ketoesters in one step. Good to
      excellent yields of the amination products were obtained under robust conditions,
      providing versatile and useful scaffolds.

PMID- 22390153
TI  - Protein expression of PKCZ (Protein Kinase C Zeta), Munc18c, and Syntaxin-4 in
      the insulin pathway in endometria of patients with polycystic ovary syndrome
      (PCOS).
AB  - BACKGROUND: Polycystic Ovary Syndrome (PCOS) is an endocrine-metabolic disorder
      commonly associated with insulin resistance (IR). Previous studies indicate about
      the expression of molecules involved in the insulin pathway in endometria of
      women with PCOS-IR. Therefore, the aim of the present study was to evaluate the
      effect of insulin and testosterone in the expression of these proteins in the
      endometria and immortal endometrial stromal cell line (T-HESCs). METHODS: We
      examined the protein levels of Munc18c, PKC zeta, phospho-PKC Zeta, and Syntaxin
      4. Protein levels were assessed by Western Blot and/or immunohistochemistry in
      proliferative endometria (NPE = 6) and in PCOS endometria with insulin resistance
      (PCOSE-IR = 6). We also evaluated whether high concentrations of insulin (100 nM)
      and/or testosterone (100 nM), during a 24 h stimulatory period, affected the
      expression of these proteins in an immortal endometrial stromal cell line (T
      HESCs). Once stimulated, proteins were extracted from cells and were assessed by
      Western Blot analysis. Immunocytochemistry was performed to detect AR in T-HESC
      cells. RESULTS: Western Blot data showed decreased expression (p < 0,05) of
      Munc18c and phospho-PKC Zeta in PCOS-IR endometria (PCOSE-IR) with respect to the
      control (NPE). In the in vitro study, Western Blot analysis showed decreased
      levels of Munc18c, PKC Zeta and phospho-PKC Zeta with the different hormonal
      treatments when compared to the control condition (no hormonal stimulation) (p <
      0,05). The AR was present in the endometrial stromal cell line (T-HESC).
      CONCLUSION: The conditions of hyperinsulinism and hyperandrogenism present in
      PCOS-IR patients modulate the expression and/or phosphorylation of the proteins
      involved in the insulin pathway at the endometrial level. These data extend to
      the T-HESCs cells results, where insulin and testosterone exert an effect on both
      the expression and phosphorylation of proteins present in the pathway.

PMID- 22390155
TI  - Cobalt-centered ten-vertex germanium clusters: the pentagonal prism as an
      alternative to polyhedra predicted by the Wade-Mingos rules.
AB  - One of the most exciting recent (2009) discoveries in metal cluster chemistry is
      the pentagonal prismatic Co@Ge(10)(3-) ion, found in [K(2,2,2
      crypt)](4)[Co@Ge(10)][Co(1,5-C(8)H(12))(2)].toluene and characterized
      structurally by X-ray diffraction. The complete absence of triangular faces in
      the pentagonal prismatic structure of Co@Ge(10)(3-) contradicts expectations from
      the well-established Wade-Mingos rules, which predict polyhedral structures
      having mainly or entirely triangular faces. A theoretical study on Co@Ge(10)(z)
      systems (z = -5 to +1) predicts a singlet D(5h) pentagonal prismatic global
      minimum for the trianion Co@Ge(10)(3-) in accord with this experimental result.
      Redox reactions on this pentagonal prismatic Co@Ge(10)(3-) trianion generate low
      energy pentagonal prismatic structures for Co@Ge(10)(z) where z = 0, -1, -2, -4,
      and -5 having quartet, triplet, doublet, doublet, and triplet spin states,
      respectively. Similar theoretical methods predict a singlet C(3v) polyhedral
      structure for the monoanion Co@Ge(10)(-), similar to previous theoretical
      predictions on the isoelectronic neutral Ni@Ge(10) and the structure realized
      experimentally in the isoelectronic Ni@In(10)(10-) found in the K(10)In(10)Ni
      intermetallic. Redox reactions on this C(3v) polyhedral Co@Ge(10)(-) monoanion
      generate low energy C(3v) polyhedral structures for Co@Ge(10)(z) where z = 0, -2,
      -3, and -4 having doublet, doublet, triplet, and quartet spin states,
      respectively.

PMID- 22390156
TI  - Incidence, risk factors and prognosis of acute kidney injury after transcatheter
      aortic valve implantation.
AB  - AIM:   Transcatheter aortic valve implantation (TAVI) poses a significant risk of
      acute kidney injury (AKI). Little is known of the impact of TAVI and AKI on long
      term kidney function and health cost. We explored the predictive factors and
      prognostic implications of AKI following TAVI. METHODS:   Single-centre
      retrospective analysis of 52 elderly patients undergoing TAVI was conducted. The
      primary endpoint was renal outcome which included the incidence of AKI and 12
      month renal function after TAVI. Secondary endpoints were mortality, the length
      of hospital stay (LOS) and cost. RESULTS:   AKI occurred in 15/52 (28.8%)
      patients (mean age 84 +/- 6) and three patients (6%) required dialysis. Patients
      with AKI (AKI+) had greater comorbidity (diabetes and cerebrovascular disease)
      and a trend towards reduced estimated glomerular filtration rate (eGFR) at
      baseline compared with those without AKI (56.6 vs AKI-: 65.7 mL/min per 1.73 m(2)
      , P = 0.07). Following TAVI, AKI- patients experienced an immediate improvement
      in eGFR, which remained significantly higher at all time points compared with
      AKI+ patients (70.4 vs 46.9 at 6 months and 73.7 vs 53.0 at 12 months, P <
      0.001). Cumulative mortality for AKI+versus AKI- group was 26.7% and 2.7% (P =
      0.006). LOS doubled (P < 0.001) and average hospitalization cost per patient was
      1.5 times higher in the AKI+ group (P < 0.001). Independent predictors of AKI
      were peri-procedural blood transfusion (OR: 2.4, 95% CI: 2.0-3.1), trans-apical
      approach (OR: 9.3, 95% CI: 4.3-23.7) and hypertension (OR: 6.4, 95% CI: 2.9
      17.3). CONCLUSION:   AKI developed in 28.8% of patients after TAVI and was
      associated with procedural technique and transfusion requirement, and an
      increased LOS and mortality. However, most patients achieved a significant and
      sustained improvement in eGFR.

PMID- 22390157
TI  - Downregulation of TGF-betaRII in T effector cells leads to increased resistance
      to TGF-beta-mediated suppression of autoimmune responses in type I diabetes.
AB  - Tregs play an important role in controlling immune responses, particularly
      autoimmunity. In NOD mouse model, an excellent model for autoimmune diabetes,
      transfer of Tregs was shown to prevent diabetes, whereas depletion of Tregs in
      vivo enhanced disease progression, suggesting that Treg dysfunction contributes
      to the pathogenesis of diabetes. However, the mechanisms leading to Treg
      dysfunction and their role in diabetes progression has remained unclear. In this
      study we assessed quantitative and qualitative changes in Tregs during the
      development of autoimmune diabetes in NOD. We compared female NOD with males that
      have similar predisposition to but a lower incidence of diabetes and found that
      Treg numbers remained unchanged between 6 to 16 weeks of age in both groups.
      Although female Tregs produced lower TGF-beta compared to male, regulatory
      function of female Tregs was only marginally inferior to male upon GAD65
      autoantigen stimulation. GAD65-reactive female Teffectors were more responsive
      and progressively became refractory to regulation compared to male effectors, in
      part due to lower expression of TGF-beta RII, accounting for reduced sensitivity
      to Tregs. Moreover, we unexpectedly found that TGF-beta suppressed IFN-gamma
      production to GAD65 antigen in male, not in female responders. These data suggest
      that TGF-beta plays a major role in Teff resistance to regulation and Treg
      dysfunction, and may account for autoimmune diabetes. Our study implies that
      development of a successful supplemental Treg therapy for halting autoimmunity
      may require further understanding of Teff responses to regulation in order to
      generate highly effective Tregs.

PMID- 22390158
TI  - Acute onset of dyspnea associated with Oslerus osleri infection in a dog.
AB  - OBJECTIVE: To describe an unusual clinical presentation of Oslerus osleri
      infection in the dog and to review current diagnostic and treatment strategies
      for this infection. CASE SUMMARY: A 2-year-old Briard presented as an emergency
      for evaluation of acute respiratory distress. Radiographs of the thorax revealed
      an intratracheal masses near the bifurcation of the trachea. Biopsies of the
      masses identified parasitic fragments consistent with O. osleri infection. The
      patient was successfully treated with fenbendazole and the patient's clinical
      signs have not reoccurred over the last 5 months. UNIQUE INFORMATION PROVIDED:
      This report documents an uncommon presentation of acute respiratory distress
      associated with O. osleri infection in the dog, as previously reported cases
      usually report a history of chronic cough. In this case, the patient presented
      with an acute onset of dyspnea and no history of chronic cough suggesting that O.
      osleri infection may be a consideration in any young dog presented with acute
      respiratory distress.

PMID- 22390159
TI  - Assessment of public health impact of work-related asthma.
AB  - BACKGROUND: Asthma is among the most common chronic diseases in working-aged
      populations and occupational exposures are important causal agents. Our aims were
      to evaluate the best methods to assess occurrence, public health impact, and
      burden to society related to occupational or work-related asthma and to achieve
      comparable estimates for different populations. METHODS: We addressed three
      central questions: 1: What is the best method to assess the occurrence of
      occupational asthma? We evaluated: 1) assessment of the occurrence of
      occupational asthma per se, and 2) assessment of adult-onset asthma and the
      population attributable fractions due to specific occupational exposures. 2: What
      are the best methods to assess public health impact and burden to society related
      to occupational or work-related asthma? We evaluated methods based on assessment
      of excess burden of disease due to specific occupational exposures. 3: How to
      achieve comparable estimates for different populations? We evaluated
      comparability of estimates of occurrence and burden attributable to occupational
      asthma based on different methods. RESULTS: Assessment of the occurrence of
      occupational asthma per se can be used in countries with good coverage of the
      identification system for occupational asthma, i.e. countries with well
      functioning occupational health services. Assessment based on adult-onset asthma
      and population attributable fractions due to specific occupational exposures is a
      good approach to estimate the occurrence of occupational asthma at the population
      level. For assessment of public health impact from work-related asthma we
      recommend assessing excess burden of disease due to specific occupational
      exposures, including excess incidence of asthma complemented by an assessment of
      disability from it. International comparability of estimates can be best achieved
      by methods based on population attributable fractions. CONCLUSIONS: Public health
      impact assessment for occupational asthma is central in prevention and health
      policy planning and could be improved by purposeful development of methods for
      assessing health benefits from preventive actions. Registry-based methods are
      suitable for evaluating time-trends of occurrence at a given population but for
      international comparisons they face serious limitations. Assessment of excess
      burden of disease due to specific occupational exposure is a useful measure, when
      there is valid information on population exposure and attributable fractions.

PMID- 22390160
TI  - How to manage invasive procedures in children with haemophilia.
AB  - Invasive procedures can be performed safely in children with haemophilia due to
      the availability of factor VIII/IX for patients without inhibitors. Most
      guidelines are based on the experiences in adults, but still there is no
      established consensus on the optimal factor levels or duration of replacement
      therapy for adults undergoing surgery. Few publications have focused on surgery
      in children with haemophilia. Children who have developed inhibitors to factor
      VIII/IX have to be treated with bypassing agents and constitute a group at higher
      risk for bleeding complications during surgery. The aim of this review is to
      summarize the experiences and opinions in the literature on replacement treatment
      of children with haemophilia, with and without inhibitors, during and after
      surgery, with a focus on the most prevalent clinical situations.

PMID- 22390161
TI  - The relationship between change in self-perceptions of aging and physical
      functioning in older adults.
AB  - Negative self-perceptions of aging (SPA) have been linked to poor physical health
      and functioning outcomes in late life, yet the direction of this relationship
      remain unclear. Using data from the Australian Longitudinal Study of Aging, we
      investigated the directionality of the dynamic relationship between self
      perceptions of aging and physical functioning in 1,212 adults 65 years and above
      (mean age = 76.89, SD = 6.12) over 5 waves (up to 16 years). Bivariate Dual
      Change Score Models (BDCSM) revealed that the best fitting model for the data was
      that which allowed SPA to predict change in physical functioning over time lags
      of 1 year. The direction of the relationship remained after controlling for age,
      gender, partner status, residential care, number of medical conditions, self
      rated health, and psychological well-being. Findings suggest that more positive
      SPA may be protective of decline in physical functioning in late life.

PMID- 22390162
TI  - Perceptions of structural empowerment: differences between nationally certified
      perinatal nurses and perinatal nurses who are not nationally certified.
AB  - BACKGROUND: Although there has been previous research linking perceptions of
      empowerment to specialty certification among critical care nurses, no research in
      this area has been conducted among nationally certified perinatal nurses.
      METHODS: A comparative quantitative survey design was used. Participants included
      80 perinatal registered nurses from one community hospital in New York. RESULTS:
      Registered nurses who were nationally certified in a perinatal specialty had
      higher total empowerment scores and higher scores on five of the six subscales.
      CONCLUSION: This study supports the results of previous studies focused on
      differences in empowerment among nationally certified nurses and nurses without
      national certification. Because much of the preparation for certification is done
      within continuing education, nurse leaders must be cognizant of the value of
      certification and must develop and implement programs to support certification in
      the workplace.

PMID- 22390163
TI  - Benefits of a unit-based skin care group.
AB  - The medical patient population presents with various types of wounds when
      admitted to the hospital. A clinical nurse specialist (CNS) is often consulted to
      help nurses to assess wounds and dress them appropriately. Because CNS
      consultation is available only during business hours, staff identified a need for
      a core group of nurses to be knowledgeable about wound care. To address this
      need, a skin group was developed and given additional education. The members of
      this group were able to provide several interventions geared toward the nursing
      staff. In conjunction with the unit-based CNS, the skin group members have helped
      to improve the skin and wound care that patients receive and have consistently
      delivered this care in a timely manner.

PMID- 22390164
TI  - Mutual co-regulation between GPI-N-acetylglucosaminyltransferase and ergosterol
      biosynthesis in Candida albicans.
AB  - A novel co-regulation exists between the first step of GPI
      (glycosylphosphatidylinositol) anchor biosynthesis and the rate-determining step
      of ergosterol biosynthesis in Candida albicans. Depleting CaGpi19p, an accessory
      subunit of the enzyme complex that initiates GPI biosynthesis, down-regulates
      ERG11, altering ergosterol levels and drug response. This effect is specific to
      CaGpi19p depletion and is not due to cell wall defects or GPI deficiency.
      Additionally, down-regulation of ERG11 down-regulates CaGPI19 and GPI
      biosynthesis.

PMID- 22390165
TI  - Phase transitions of n-hexadecane in nanoencapsulated binary solutions of n
      hexadecane and 1-octanol.
AB  - Binary solutions of n-hexadecane and 1-octanol were encapsulated within poly(tert
      butyl methacrylate) nanocapsules and the phase transition behavior of the n
      hexadecane studied. A sigmoidal correlation was found between the binary
      composition of the encapsulated oil and the oil formulation prior to
      encapsulation. At low 1-octanol fractions in the synthesis, almost no alcohol was
      encapsulated, but at high 1-octanol fractions, the capsules were enriched in
      alcohol. The freezing point of the encapsulated n-hexadecane was considerably
      lower than in the bulk phase. This freezing point was further reduced as the
      radius of the particle was reduced, which is expected from the Gibbs-Thompson
      equation. The extracted value at infinite radii was, however, 14  degrees C below
      the bulk freezing point. The colligative effect of 1-octanol on the freezing
      point of n-hexadecane, i.e., dT(f)/dx(m), where x(m) is the mass fraction of 1
      octanol, was nearly identical to that measured in the bulk system. The specific
      enthalpy of freezing for the encapsulated system was considerably different from
      the bulk system. In the bulk system, the freezing enthalpy for n-hexadecane was
      nearly constant up to 60% mass of 1-octanol. The freezing enthalpy for the
      encapsulated n-hexadecane showed greater variation with % mass 1-octanol, and had
      a considerably lower absolute value than the bulk system.

PMID- 22390166
TI  - Purification and high-resolution top-down mass spectrometric characterization of
      human salivary alpha-amylase.
AB  - Human salivary alpha-amylase (HSAMY) is a major component of salivary secretions,
      possessing multiple important biological functions. Here we have established
      three methods to purify HSAMY in human saliva for comprehensive characterization
      of HSAMY by high-resolution top-down mass spectrometry (MS). Among the three
      purification methods, the affinity method based on the enzyme-substrate specific
      interaction between amylase and glycogen is preferred, providing the highest
      purity HSAMY with high reproducibility. Subsequently, we employed Fourier
      transform ion cyclotron resonance MS to analyze the purified HSAMY. The
      predominant form of alpha-amylase purified from saliva of various races and
      genders is nonglycosylated with the same molecular weight of 55,881.2, which is
      1885.8 lower than the calculated value based on the DNA-predicted sequence. High
      resolution MS revealed the truncation of the first 15 N-terminal amino acids (
      1858.96) and the subsequent formation of pyroglutamic acid at the new N-terminus
      Gln (-17.03). More importantly, five disulfide bonds in HSAMY were identified (
      10.08) and effectively localized by tandem MS in conjunction with complete and
      partial reduction by tris (2-carboxyethyl) phosphine. Overall, this study
      demonstrates that top-down MS combined with affinity purification and partial
      reduction is a powerful method for rapid purification and complete
      characterization of large proteins with complex and overlapping disulfide bond
      patterns.

PMID- 22390168
TI  - On the reaction mechanism of tirapazamine reduction chemistry: unimolecular N-OH
      homolysis, stepwise dehydration, or triazene ring-opening.
AB  - The initial steps of the activation of tirapazamine (TPZ, 1, 3-amino-1,2,4
      benzotriazine 1,4-N,N-dioxide) under hypoxic conditions consist of the one
      electron reduction of 1 to radical anion 2 and the protonation of 2 at O(N4) or
      O(N1) to form neutral radicals 3 and 4, respectively. There are some questions,
      however, as to whether radicals 3 and/or 4 will then undergo N-OH homolyses 3 ->
      5 + .OH and 4 -> 6 + .OH or, alternatively, whether 3 and/or 4 may react by
      dehydration and form aminyl radicals via 3 -> 11 + H(2)O and 4 -> 12 + H(2)O or
      phenyl radicals via 3 -> 17 + H(2)O. These outcomes might depend on the chemistry
      after the homolysis of 3 and/or 4, that is, dehydration may be the result of a
      two-step sequence that involves N-OH homolysis and formation of .OH aggregates of
      5 and 6 followed by H-abstraction within the .OH aggregates to form hydrates of
      aminyls 11 and 12 or of phenyl 17. We studied these processes with configuration
      interaction theory, perturbation theory, and density functional theory. All
      stationary structures of OH aggregates of 5 and 6, of H(2)O aggregates of 11, 12,
      and 17, and of the transition state structures for H-abstraction were located and
      characterized by vibrational analysis and with methods of electron and spin
      density analysis. The doublet radical 17 is a normal spin-polarized radical,
      whereas the doublet radicals 11 and 12 feature quartet instabilities. The
      computed reaction energies and activation barriers allow for dehydration in
      principle, but the productivity of all of these channels should be low for
      kinetic and dynamic reasons. With a view to plausible scenarios for the
      generation of latent aryl radical species without dehydration, we scanned the
      potential energy surfaces of 2-4 as a function of the (O)N1-Y (Y = C5a, N2) and
      (O)N4-Z (Z = C4a, C3) bond lengths. The elongation of any one of these bonds by
      0.5 A requires less than 25 kcal/mol, and this finding strongly suggests the
      possibility of bimolecular reactions of the spin-trap molecules with 2-4
      concomitant with triazene ring-opening.

PMID- 22390169
TI  - Layer-by-layer assembly of partially sulfonated isotactic polystyrene with
      poly(vinylamine).
AB  - The stereoregular synthetic polymer isotactic polystyrene bearing partially
      sulfonated groups (SiPS) was used as a layer-by-layer assembled thin film for the
      first time. When a low molecular weight compound was employed as the pair for the
      alternative layer-by-layer (LbL) assembly, the frequency shift was very small
      using quartz crystal microbalance (QCM) analysis, whereas poly(vinylamine) (PVAm)
      formed an effective pair for the construction of LbL films with SiPS. When it was
      neutralized, SiPS was not assembled, probably due to the loss of effective
      polymer-polymer interactions. The ionic strength conditions revealed a slight
      difference of the assembly behavior on the isotactic polymer as compared to the
      atactic one. The assembled LbL film showed the same peaks over the range from
      1141 to 1227 cm(-1) and 700 cm(-1) in the FT-IR/ATR spectra as the bulk complex
      of SiPS/PVAm, and the thickness on one side was calculated at 76 nm by QCM
      analysis. The surface roughness of the film was also observed by AFM.

PMID- 22390170
TI  - Silencing of the DEK gene induces apoptosis and senescence in CaSki cervical
      carcinoma cells via the up-regulation of NF-kappaB p65.
AB  - The human DEK proto-oncogene has been found to play an important role in
      autoimmune disease, viral infection and human carcinogenesis. Although it is
      transcriptionally up-regulated in cervical cancer, its intracellular function and
      regulation is still unexplored. In the present study, DEK and IkappaBalpha
      [inhibitor of NF-kappaB (nuclear factor kappaB) alpha] shRNAs (short hairpin
      RNAs) were constructed and transfected into CaSki cells using LipofectamineTM.
      The stable cell line CaSki-DEK was obtained after G418 selection. CaSki-IkappaB
      cells were observed at 48 h after psiRNA-IkappaB transfection. The inhibitory
      efficiency of shRNAs were detected by RT (reverse transcription)-PCR and Western
      blot analysis. The proliferation activity of cells were measured using an MTT [3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay, cell
      apoptosis was measured using an Annexin V/PI (propidium iodide) kit, the cell
      cycle was analysed by flow cytometry and cell senescence was detected using
      senescence beta-galactosidase staining. The intracellular expression of NF-kappaB
      p65 protein was studied by cytochemistry. The expression levels of NF-kappaB p65,
      p50, c-Rel, IkappaBalpha and phospho-IkappaBalpha protein were analysed by
      immunoblotting in whole-cell lysates, cytosolic fractions and nuclear extracts.
      The protein expression and activity of p38 and JNK (c-Jun N-terminal kinase) were
      also assayed. In addition, the NF-kappaB p65 DNA-binding activity was measured by
      ELISA. Following the silencing of DEK and IkappaBalpha, cell proliferation was
      inhibited, apoptosis was increased, the cell cycle was blocked in the G0/G1-phase
      with a corresponding decrease in the G2/M-phase, and cell senescence was induced.
      All of these effects may be related to the up-regulation of NF-kappaB p65
      expression and its nuclear translocation.

PMID- 22390171
TI  - Mutasynthesis of a potent anticancer sibiromycin analogue.
AB  - Pursuit of the actinomycete pyrrolobenzodiazepine natural product sibiromycin as
      a chemotherapeutic agent has been limited by its cardiotoxicity. Among
      pyrrolobenzodiazepines, cardiotoxicity is associated with hydroxylation at
      position 9. Deletion of the methyltransferase gene sibL abolishes the production
      of sibiromycin. Supplementation of growth media with 4-methylanthranilic acid can
      substitute for its native 3-hydroxy congener. Cultures grown in this fashion
      yielded 9-deoxysibiromycin. In this study, we characterize the structure and
      biological activity of sibiromycin and 9-deoxysibiromycin methyl carbinolamines.
      Preliminary in vitro evidence suggests that 9-deoxysibiromycin exhibits reduced
      cardiotoxicity while gaining antitumor activity. These results strongly support
      further exploration of the production and evaluation of monomeric and dimeric
      glycosylated pyrrolobenzodiazepine analogues of sibiromycin.

PMID- 22390172
TI  - Asymmetric total synthesis of (+)-virosine A via sequential nucleophilic
      cyclizations onto an activated formamide.
AB  - The first synthesis of tetracyclic alkaloid virosine A is reported. The natural
      alkaloid was prepared in only 13 steps, in an enantioenriched form. The
      azabicyclo[2.2.2]octane core was efficiently assembled using a key Vilsmeier
      Haack and Mannich cyclizations sequence performed in one pot.

PMID- 22390174
TI  - My word! Interference from reading object names implies a role for competition
      during picture name retrieval.
AB  - A related word prime has been found to interfere with picture naming after
      unrelated intervening trials (word-to-picture interference). Recently, Stroop
      type picture-word interference effects have been interpreted in terms of a
      postlexical response exclusion process rather than a competitive lexical
      selection process. An experiment is reported that examines whether word-to
      picture effects could reflect response exclusion mechanisms and, more generally,
      strategic processing of the word prime. Forty-eight volunteer university students
      named aloud sequences of semantically related (and unrelated) word primes and
      picture targets, separated by two unrelated filler stimuli. On half of the
      trials, participants were asked to count backwards in threes from a random number
      presented immediately after naming the prime word. They were also given a
      surprise recall test at the end of the naming block. Results for naming times and
      errors indicated a main effect of relatedness; semantic interference effects were
      not dependent on the unfilled gap following the word prime trial and were also
      not tied to episodic recall of prime words. The data indicate that slowed picture
      naming times are more likely to emerge from processes intrinsic to word prime
      naming rather than controlled processing and do not readily fit the postlexical
      response exclusion account. The results are considered in relation to two recent
      accounts of interference over unrelated trials, which refer to some form of
      competition at, or prior to, lexical access.

PMID- 22390173
TI  - The bar sinister: does handlebar level damage the pelvic floor in female
      cyclists?
AB  - INTRODUCTION: Cycling is associated with genital neuropathies and erectile
      dysfunction in males. Women riders also have decreased genital sensation;
      however, sparse information exists addressing the effects of modifiable risks on
      neurological injuries in females. AIM: This study assesses the effects of bicycle
      setup and cyclists' attributes on GS and saddle pressures among female cyclists.
      METHODS: Previously, we compared genital sensation in competitive female cyclists
      (N = 48) to that of female runners (N = 22). The current study is a subanalysis
      of the 48 cyclists from the original study group. Nonpregnant, premenopausal
      women who rode at least 10 miles per week, 4 weeks per month were eligible for
      participation. MAIN OUTCOME MEASURES: Genital sensation was measured in microns
      using biosthesiometry measures of vibratory thresholds (VTs). Perineal and total
      saddle pressures were determined using a specialized pressure map and recorded in
      kilopascals (kPA). RESULTS: Handlebars positioned lower than the saddle
      correlated with increased perineum saddle pressures and decreased anterior
      vaginal and left labial genital sensation (P < 0.05, P < 0.02, P < 0.03,
      respectively). Low handlebars were not associated with total saddle pressures or
      altered genital sensation in other areas. After adjusting for age and saddle
      type, low handlebars were associated with a 3.47-kPA increase in mean perineum
      saddle pressures (P < 0.04) and a 0.86-micron increase in anterior vagina VT (P <
      0.01). CONCLUSION: Handlebars positioned lower than the saddle were significantly
      associated with increased perineum saddle pressures and decreased genital
      sensation in female cyclists. Modifying bicycle setup may help alleviate
      neuropathies in females. Additional research is warranted to further assess the
      extent of the associations.

PMID- 22390175
TI  - Syntheses and excitation transfer studies of near-orthogonal free-base porphyrin
      ruthenium phthalocyanine dyads and pentad.
AB  - A new series of molecular dyads and pentad featuring free-base porphyrin and
      ruthenium phthalocyanine have been synthesized and characterized. The synthetic
      strategy involved reacting free-base porphyrin functionalized with one or four
      entities of phenylimidazole at the meso position of the porphyrin ring with
      ruthenium carbonyl phthalocyanine followed by chromatographic separation and
      purification of the products. Excitation transfer in these donor-acceptor polyads
      (dyad and pentad) is investigated in nonpolar toluene and polar benzonitrile
      solvents using both steady-state and time-resolved emission techniques.
      Electrochemical and computational studies suggested that the photoinduced
      electron transfer is a thermodynamically unfavorable process in nonpolar media
      but may take place in a polar environment. Selective excitation of the donor,
      free-base porphyrin entity, resulted in efficient excitation transfer to the
      acceptor, ruthenium phthalocyanine, and the position of imidazole linkage on the
      free-base porphyrin could be used to tune the rates of excitation transfer. The
      singlet excited Ru phthalocyanine thus formed instantly relaxed to the triplet
      state via intersystem crossing prior to returning to the ground state. Kinetics
      of energy transfer (k(ENT)) was monitored by performing transient absorption and
      emission measurements using pump-probe and up-conversion techniques in toluene,
      respectively, and modeled using a Forster-type energy transfer mechanism. Such
      studies revealed the experimental k(ENT) values on the order of 10(10)-10(11) s(
      1), which readily agreed with the theoretically estimated values. Interestingly,
      in polar benzonitrile solvent, additional charge transfer interactions in the
      case of dyads but not in the case of pentad, presumably due to the
      geometry/orientation consideration, were observed.

PMID- 22390176
TI  - Endoplasmic reticulum stress plays an important role in amyotrophic lateral
      sclerosis (commentary on Prell et al.).

PMID- 22390177
TI  - The unfolded protein response in models of human mutant G93A amyotrophic lateral
      sclerosis.
AB  - Recent studies indicate that endoplasmic reticulum (ER) stress is involved in the
      pathogenesis of familial and sporadic amyotrophic lateral sclerosis (ALS). ER
      stress occurs when the ER-mitochondria calcium cycle (ERMCC) is disturbed and
      misfolded proteins accumulate in the ER. To cope with ER stress, the cell engages
      the unfolded protein response (UPR). While activation of the UPR has been shown
      in some ALS models and tissues, ER stress elements have not been studied directly
      in motor neurons. Here we investigated the expression of XBP1 and ATF6alpha and
      phosphorylation of eIF2alpha, and their modulation, in mutated SOD1(G93A)  NSC34
      and animal model of ALS. Expression of XBP1 and ATF6alpha mRNA and protein was
      enhanced in SOD1(G93A)  NSC34 cells. Activation of ATF6alpha and XBP1 and
      phosphorylation of eIF2alpha were detectable in mutated SOD1(G93A)  motor but not
      in wild-type motor neurons. Treatment with the ER stressor thapsigargin enhanced
      phosphorylation of eIF2alpha and activated proteolysis of ATF6alpha and splicing
      of XBP1 in NSC34 and motor neurons in a time-dependent manner. The present study
      thus provides direct evidence of activated UPR in motor neurons which overexpress
      human pathogenic mutant SOD1(G93A) , providing evidence that ER stress plays a
      major role in ALS.

PMID- 22390178
TI  - Both NKCC1 and anion exchangers contribute to Cl- accumulation in postnatal
      forebrain neuronal progenitors.
AB  - Neuronal progenitors are continuously generated in the postnatal rodent
      subventricular zone and migrate along the rostral migratory stream to supply
      interneurons in the olfactory bulb. Nonsynaptic GABAergic signaling affects the
      postnatal neurogenesis by depolarizing neuronal progenitors, which depends on an
      elevated intracellular Cl(-) concentration. However, the molecular mechanism
      responsible for Cl(-) accumulation in these cells still remains elusive. Using
      confocal Ca(2+) imaging, we found that GABA depolarization-induced Ca(2+)
      increase was either abolished by bumetanide, a specific inhibitor of the Na(+) 
      K(+) -2Cl(-) cotransporter, or reduced by partial replacement of extracellular
      Na(+) with Li(+) , in the HEPES buffer but not in the CO(2)/HCO3- buffer. GABA
      depolarization-induced Ca(2+) increase in CO(2)/HCO3- buffer was abolished by a
      combination of bumetanide with the anion exchanger inhibitor DIDS or with the
      carbonic anhydrase inhibitor acetozalimide. Using gramicidin-perforated patch
      clamp recording, we further confirmed that bumetanide, together with DIDS or
      acetozalimide, reduced the intracellular chloride concentration in the neuronal
      progenitors. In addition, with BrdU labeling, we demonstrated that blocking of
      the Na(+) -K(+) -2Cl(-) cotransporter, but not anion exchangers, reduced the
      proliferation of neuronal progenitors. Our results indicate that both the Na(+) 
      K(+) -2Cl(-) cotransporter and anion exchangers contribute to the elevated
      intracellular chloride responsible for the depolarizing action of GABA in the
      postnatal forebrain neuronal progenitors. However, the Na(+) -K(+) -2Cl(-)
      cotransporter displays an additional effect on neuronal progenitor proliferation.

PMID- 22390179
TI  - Prolonged survival of allogeneic islets in cynomolgus monkeys after short-term
      triple therapy.
AB  - Preclinical studies in nonhuman primates (NHP) are particularly useful to
      evaluate the safety and efficacy of new therapeutic proteins developed for use in
      clinical transplantation. We hypothesized that a treatment that selectively
      destroys activated cytopathic donor reactive T cells while sparing resting and
      immunoregulatory T cells in a mouse model might also produce long-term drug-free
      engraftment and tolerance without the hazards of lymphopenia in the challenging
      nonhuman primate islet allograft model. Short-term treatment with a regimen
      consisting of rapamycin, and IL-2.Ig plus mutant antagonist-type IL-15.Ig
      cytolytic fusion proteins (triple therapy) posttransplantation results in
      prolonged, drug-free engraftment of cynomolgus islet allografts. Moreover slow
      progressive loss of islet function in some recipients was not associated with
      obvious pathologic evidence of rejection.

PMID- 22390180
TI  - Examination of heterogeneous crossing sequences between toner and rollerball pen
      strokes by digital microscopy and 3-D laser profilometry.
AB  - The determination of line crossing sequences between rollerball pens and laser
      printers presents difficulties that may not be overcome using traditional
      techniques. This research aimed to study the potential of digital microscopy and
      3-D laser profilometry to determine line crossing sequences between a toner and
      an aqueous ink line. Different paper types, rollerball pens, and writing pressure
      were tested. Correct opinions of the sequence were given for all case scenarios,
      using both techniques. When the toner was printed before the ink, a light
      reflection was observed in all crossing specimens, while this was never observed
      in the other sequence types. The 3-D laser profilometry, more time-consuming,
      presented the main advantage of providing quantitative results. The findings
      confirm the potential of the 3-D laser profilometry and demonstrate the
      efficiency of digital microscopy as a new technique for determining the sequence
      of line crossings involving rollerball pen ink and toner.

PMID- 22390181
TI  - Management of male infertility due to congenital bilateral absence of vas
      deferens should not ignore the diagnosis of cystic fibrosis.
AB  - Microsurgical or percutaneous epididymal sperm aspiration and intracytoplasmic
      sperm injection (ICSI) are proposed to overcome male infertility due to
      congenital bilateral absence of vas deferens (CBAVD). CBAVD has been associated
      with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)
      gene and consequently, genetic counselling has to be addressed before beginning
      ICSI procedure. However, management of male infertility due to CBAVD should not
      ignore a mild form of cystic fibrosis. We describe the case of cystic fibrosis
      late diagnosis performed in a 49-year-old infertile men with CBAVD. CFTR
      molecular testing detected two mutations F508del and A455E corresponding to a
      cystic fibrosis genotype. Pneumological evaluation revealed a severe obstructive
      respiratory disease, bronchiectasis and high sweat chloride levels. Symptoms
      consistent with a cystic fibrosis have to be identified in infertile men with
      CBAVD before beginning assisted reproductive procedures.

PMID- 22390182
TI  - Germinal center B-cells.
AB  - Within the B-cell follicle of secondary lymphoid organs, germinal center (GC)
      reactions produce high affinity antibody-secreting plasma cells (PCs) and memory
      B-cells necessary for the host's defense against invading pathogens. This process
      of GC formation is reliant on the activation of antigen-specific B-cells by T
      cells capable of recognizing epitopes of the same antigenic complex. The unique
      architecture of secondary lymphoid organs facilitates these initial GC events
      through the placement of large clonally-diverse B-cell follicles near equally
      diverse T-cell zones. Antigen-activated B-cells that receive proper
      differentiation signals at the T-cell border of the B-cell follicle initiate an
      early GC B-cell transcriptional profile and migrate to follicular dendritic cell
      (FDC) networks within the B-cell follicle to seed the GC reaction. Peripheral to
      FDCs, GC B-cells rapidly divide in dark zones of the GC, and undergo somatic
      hypermutation of their immunoglobulin (Ig) variable domain. Newly formed GC B
      cell clones then migrate into the GC light zone where they compete for antigen
      and secondary signals presented by FDCs and a specialized subset of CD4(+) T
      cells known as T-follicular helper (T(FH)) cells. Survival, proliferative and
      differentiation signals delivered by mature FDCs and T(FH) cells initiate
      transcriptional programs that determine if GC B-cells become memory B-cells or
      terminally differentiated PCs. To prevent oncogenic transformation and/or the
      escape of autoreactive clones, there are several regulatory mechanisms that
      restrict GC B-cell proliferation and survival. Here we will detail the recent
      advances in GC B-cell biology that relate to their generation and fate
      determination as well as their pathogenic potential.

PMID- 22390183
TI  - Fair reckoning: a qualitative investigation of responses to an economic health
      resource allocation survey.
AB  - OBJECTIVE: To investigate how participants in an economic resource allocation
      survey construct notions of fairness. DESIGN: Qualitative interview study guided
      by interpretive grounded theory methods. SETTING AND PARTICIPANTS: Qualitative
      interviews were conducted with volunteer university- (n=39) and community-based
      (n =7) economic survey participants. INTERVENTION OR MAIN VARIABLES STUDIED: We
      explored how participants constructed meanings to guide or explain fair survey
      choices, focusing on rationales, imagery and additional desired information not
      provided in the survey scenarios. MAIN OUTCOME MEASURES: Data were transcribed
      and coded into qualitative categories. Analysis iterated with data collection
      iterated through three waves of interviews. RESULTS: Participants compared the
      survey dilemmas to domains outside the health system. Most compared them with
      other micro-level, inter-personal sharing tasks. Participants raised several
      fairness-relevant factors beyond need or capacity to benefit. These included age,
      weight, poverty, access to other options and personal responsibility for illness;
      illness duration, curability or seriousness; life expectancy; possibilities for
      sharing; awareness of other's needs; and ability to explain allocations to those
      affected. They also articulated a fairness principle little considered by equity
      theories: that everybody must get something and nobody should get nothing.
      DISCUSSION AND CONCLUSIONS: Lay criteria for judging fairness are myriad. Simple
      scenarios may be used to investigate lay commitments to abstract principles.
      Although principles are the focus of analysis and inference, participants may
      solve simplified dilemmas by imputing extraneous features to the problem or
      applying unanticipated principles. These possibilities should be taken into
      account in the design of resource allocation surveys eliciting the views of the
      public.

PMID- 22390184
TI  - Use of lispro insulin for treatment of diabetic ketoacidosis in dogs.
AB  - OBJECTIVES: To characterize the use of lispro insulin in dogs with diabetes
      ketoacidosis (DKA) and to compare the length of time required for resolution of
      hyperglycemia, ketosis, and acidosis, respectively, in dogs with DKA treated with
      lispro or with regular insulin. DESIGN: Randomized prospective clinical trial
      performed between November 2006 and May 2009. SETTING: University teaching
      hospital. ANIMALS: Client-owned dogs with naturally occurring DKA. Dogs with a
      blood glucose (BG) > 13.9 mmol/L (>250 mg/dL), blood pH between 7.0 and 7.35, and
      a blood beta-hydroxybutyrate (BOHB) concentration >2.0 mmol/L were eligible to be
      enrolled into the study and were randomly assigned to receive an IV continuous
      rate infusion (CRI) of either lispro or regular insulin. INTERVENTIONS: Lispro or
      regular insulin was administered as an IV CRI at an initial dose of 0.09 U/kg/h.
      The dose was adjusted according to a previously published protocol. MEASUREMENTS
      AND MAIN RESULTS: Twelve dogs were enrolled into the study. The time to
      biochemical resolution of DKA was defined as the time interval from when the IV
      CRI of insulin began until marked hyperglycemia (BG > 13.9 mmol/L [>250 mg/dL]),
      acidosis (venous pH < 7.35), and ketosis (BOHB concentration >2.0 mmol/L)
      resolved. The median time to biochemical resolution of DKA in dogs treated with
      lispro insulin was significantly shorter (26 h; range 26-50 h) than in dogs
      treated with regular insulin (61 h; range, 38-80 h, P = 0.02). Median admission
      blood glucose concentration of all 12 dogs (24 mmol/L [432 mg/dL; range, 17.8
      38.9 mmol/L [321-700 mg/dL]) decreased significantly with fluid resuscitation and
      prior to insulin therapy (20.5 mmol/L [369 mg/dL; range, 14.5-33.3 mmol/L [261
      600 mg/dL], P = 0.0085). No adverse effects were observed in association with IV
      lispro insulin administration. CONCLUSIONS: Treatment of DKA in dogs with IV CRI
      lispro insulin is safe, and as effective as treatment with regular insulin.

PMID- 22390185
TI  - Approaches to developing the capacity of health policy analysis institutes: a
      comparative case study.
AB  - OBJECTIVES: To review and assess (i) the factors that facilitate the development
      of sustainable health policy analysis institutes in low and middle income
      countries and (ii) the nature of external support for capacity development
      provided to such institutes. METHODS: Comparative case studies of six health
      policy analysis institutes (3 from Asia and 3 from Africa) were conducted. In
      each region an NGO institute, an institute linked to government and a university
      based institute were included. Data collection comprised document review, semi
      structured interviews with stakeholders and discussion of preliminary findings
      with institute staff. FINDINGS: The findings are organized around four key
      themes: (i) Financial resources: three of the institutes had received substantial
      external grants at start-up, however two of these institutes subsequently
      collapsed. At all but one institute, reliance upon short term, donor funding,
      created high administrative costs and unpredictability. (ii) Human resources: the
      retention of skilled human resources was perceived to be key to institute success
      but was problematic at all but one institute. In particular staff often moved to
      better paid positions elsewhere once having acquired necessary skills and
      experience, leaving remaining senior staff with heavy workloads. (iii) Governance
      and management: board structures and roles varied according to the nature of
      institute ownership. Boards made important contributions to organizational
      capacity through promoting continuity, independence and fund raising. Routine
      management systems were typically perceived to be strong. (iv) Networks: linkages
      to policy makers helped promote policy influences. External networks with other
      research organizations, particularly where these were longer term institutional
      collaborations helped promote capacity. CONCLUSIONS: The development of strong in
      country analytical and research capacity to guide health policy development is
      critical, yet many health policy analysis institutes remain very fragile. A
      combination of more strategic planning, active recruitment and retention
      strategies, and longer term, flexible funding, for example through endowments,
      needs to be promoted. Specific recommendations to funders and institutes are
      provided.

PMID- 22390186
TI  - Outcome of in vitro fertilization following stimulation with highly purified hMG
      or recombinant FSH in downregulated women of advanced reproductive age: a
      prospective, randomized and controlled trial.
AB  - OBJECTIVE: To compare highly purified human menopausal gonadotropin (HP-hMG) with
      recombinant follicle-stimulating hormone (rFSH) on ovarian response and pregnancy
      outcome in downregulated women of advanced reproductive age. DESIGN: A
      prospective, randomized and controlled study of 127 consecutive normogonadotropic
      infertile women >= 35 years old undergoing their first in vitro
      fertilization/intracytoplasmic sperm injection cycles received ovarian
      stimulation with HP-hMG (n = 63) or with rFSH (n = 64) in a long gonadotropin
      releasing hormone agonist protocol. RESULTS: More leading (>= 18 mm) follicles
      and oocytes were obtained in rFSH group (p = 0.008 and p < 0.001, respectively).
      The proportion of top-quality embryo from oocyte retrieval and live birth rate
      per started cycle trended towards improvement with HP-hMG (OR 1.3, 95% CI 0.9
      1.8; OR 1.9, 95% CI 0.9-3.9; respectively), although they were not significant
      difference between two groups. At end of stimulation, higher serum progesterone
      level was found in rFSH group (p < 0.001). CONCLUSION: Following downregulated
      women of advanced reproductive age, superiority of HP-hMG over rFSH in live birth
      rate could not be concluded from this study, but noninferiority was established.
      Pharmacodynamic differences in follicular development, oocyte/embryo quality and
      endocrine response exist between HP-hMG and rFSH, which may be relevant to
      treatment outcome.

PMID- 22390187
TI  - Colonic micropapillary carcinoma, a recently recognized subtype associated with
      histological adverse factors: clinicopathological analysis of 15 cases.
AB  - AIM: Micropapillary carcinoma (MPC) is regarded as an aggressive variant of
      adenocarcinoma in any location. The reported proportion of a micropapillary
      carcinoma component in an entire tumour ranges from 5 to 95% and only one case of
      pure MPC has been reported. To date, approximately 130 cases of MPC in the
      colorectum have been reported, but it is likely that this small number is to some
      extent due to under-reporting because this pattern is not well recognized by the
      general pathologist. All previous studies have combined colonic and rectal
      primary tumours and most have only analysed patients with clinical Stages I or
      II. METHOD: We analysed 15 cases of MPC of the colon alone, diagnosed in our
      institution, and compared them with 105 conventional carcinomas of the colon.
      RESULTS: An MPC component was present in 10% of all colonic carcinomas. These
      tumours presented at a median age of 56 years, and all were of American Joint
      Committee on Cancer Stages III and IV. Subserosal tissue invasion was present in
      every case, 60% had more than four positive lymph nodes, 60% were accompanied by
      poorly differentiated conventional carcinoma, 40% had had an incomplete resection
      and a third demonstrated lymphovascular invasion. Despite these adverse
      prognostic factors, tumours containing MPC showed the same survival, stage by
      stage, as conventional adenocarcinoma in multivariate analysis, although 3-year
      survival (81.7%vs 87.3%, P=0.035) was worse on univariate analysis. CONCLUSION:
      The histopathologist should be aware of the possibility of MPC. Three-year
      survival is worse than in patients with conventional colonic carcinomas in Stage
      III.

PMID- 22390188
TI  - Outcome of Pneumocystis jirovecii pneumonia diagnosed by polymerase chain
      reaction in patients without human immunodeficiency virus infection.
AB  - BACKGROUND AND OBJECTIVE: Pneumonia caused by Pneumocystis jirovecii (PCP) in
      patients without human immunodeficiency virus (HIV) infection is associated with
      high mortality. The diagnosis of PCP at our institution is based on detection of
      DNA using a polymerase chain reaction (PCR) assay. The aim of this study was to
      describe the clinical manifestations, outcomes and factors associated with
      mortality due to PCP, as diagnosed by PCR, in patients without HIV infection.
      METHODS: Over a 6-year period, all HIV-negative immunocompromised patients
      suspected of having an opportunistic pulmonary infection underwent diagnostic
      bronchoscopy. A multigene PCR assay that detects Pneumocystis jirovecii DNA was
      used for the diagnosis of PCP. Patients were considered to have PCP if they had
      underlying immunodeficiency, compatible signs and symptoms, abnormal radiological
      findings, and Pneumocystis jirovecii DNA was detected in a bronchoalveolar lavage
      fluid sample. Data was collected retrospectively. RESULTS: PCP was diagnosed in
      58 patients. The underlying conditions included haematological malignancies
      (60.3%), solid tumours (17.2%) and immunosuppressive treatment (22.4%). The most
      common clinical features in patients with PCP were fever (94.6%), dyspnoea
      (67.2%) and cough (36.2%). The overall in-hospital mortality was 17.2% (10/58).
      Mortality was associated with co-infections, high lactate dehydrogenase levels,
      female gender, and higher pneumonia severity index and acute physiology and
      chronic health evaluation III scores. CONCLUSIONS: In this study, the mortality
      of HIV-negative patients with PCP was low compared with previous reports. We
      hypothesize that this finding resulted from the increased sensitivity of a PCR
      based assay, as compared with traditional methods, for the diagnosis of PCP in
      HIV-negative patients.

PMID- 22390189
TI  - Further evidence of validity of the Modified Melbourne Assessment for
      neurologically impaired children aged 2 to 4 years.
AB  - AIM: This paper reports the second phase of a study to extend the Melbourne
      Assessment for use with children with neurological impairment aged 2 to 4 years.
      The aim was to establish if (1) children's scores on the Modified Melbourne
      Assessment (MMA) and the Quality of Upper Extremity Skills Test (QUEST) showed a
      moderate to high, positive relation, (2) children had comparable behaviours for
      task and time demands on both tools, and (3) scores on the MMA could discriminate
      between children with mild, moderate, and severe levels of upper limb impairment.
      METHOD:   An observational study of 30 children (19 males, 11 females) with
      neurological impairment aged 2 to 4 years. Twenty-four children had spasticity
      (20 with a unilateral and four with a bilateral impairment) and two children
      presented with athetosis, two with ataxia, and two with hypotonia. RESULTS: A
      high, positive relation was found between children's scores on the MMA and the
      QUEST (rho=0.90; p=0.001). The clinical use of the MMA was comparable to the
      QUEST. MMA scores were able to discriminate between children's levels of upper
      limb impairment as determined by clinicians' ratings (F(2,27) =67.76, p=0.001).
      INTERPRETATION: These findings suggest the MMA can be clinically useful for
      children as young as 2.5 years and has the advantage of being valid for use with
      older children. Scores from the tool can also provide therapists with a
      quantitative means of consistently reporting level of upper limb impairment.

PMID- 22390190
TI  - The complexity of hydration of phloroglucinol: a comprehensive structural and
      thermodynamic characterization.
AB  - Hydrate formation is of great importance as the inclusion of water molecules
      affects many solid state properties and hence determines the required chemical
      processing, handling, and storage. Phloroglucinol is industrially important, and
      the observed differences in the morphology and diffuse scattering effects with
      growth conditions have been scientifically controversial. We have studied the
      anhydrate and dihydrate of phloroglucinol and their transformations by a unique
      combination of complementary experimental and computational techniques, namely,
      moisture sorption analysis, hot-stage microscopy, differential scanning
      calorimetry, thermogravimetry, isothermal calorimetry, single crystal and powder
      X-ray diffractometry, and crystal energy landscape calculations. The
      enthalpically stable dihydrate phase is unstable below 16% relative humidity (25 
      degrees C) and above 50  degrees C (ambient humidity), and the kinetics of
      hydration/dehydration are relatively rapid with a small hysteresis. A consistent
      atomistic picture of the thermodynamics of the hydrate/anhydrate transition was
      derived, consistent with the disordered single X-ray crystal structure and
      crystal energy landscape showing closely related low energy hydrate structures.
      These structures provide models for proton disorder and show stacking faults as
      intergrowth of different layers are possible. This indicates that the consequent
      variability in crystal surface features and diffuse scattering with growth
      conditions is not a practical concern.

PMID- 22390191
TI  - Simplification of biochemical models: a general approach based on the analysis of
      the impact of individual species and reactions on the systems dynamics.
AB  - BACKGROUND: Given the complex mechanisms underlying biochemical processes systems
      biology researchers tend to build ever increasing computational models. However,
      dealing with complex systems entails a variety of problems, e.g. difficult
      intuitive understanding, variety of time scales or non-identifiable parameters.
      Therefore, methods are needed that, at least semi-automatically, help to
      elucidate how the complexity of a model can be reduced such that important
      behavior is maintained and the predictive capacity of the model is increased. The
      results should be easily accessible and interpretable. In the best case such
      methods may also provide insight into fundamental biochemical mechanisms.
      RESULTS: We have developed a strategy based on the Computational Singular
      Perturbation (CSP) method which can be used to perform a "biochemically-driven"
      model reduction of even large and complex kinetic ODE systems. We provide an
      implementation of the original CSP algorithm in COPASI (a COmplex PAthway
      SImulator) and applied the strategy to two example models of different degree of
      complexity - a simple one-enzyme system and a full-scale model of yeast
      glycolysis. CONCLUSION: The results show the usefulness of the method for model
      simplification purposes as well as for analyzing fundamental biochemical
      mechanisms. COPASI is freely available at http://www.copasi.org.

PMID- 22390193
TI  - Role of interfacial water on protein adsorption at cross-linked polyethylene
      oxide interfaces.
AB  - Sum frequency generation (SFG) vibrational spectroscopy was used to study the
      structure of water at cross-linked PEO film interfaces in the presence of human
      serum albumin (HSA) protein. Although PEO is charge neutral, the PEO film/water
      interface exhibited an SFG signal of water similar to that of a highly charged
      water/silica interface, signifying the presence of ordered water. Ordered water
      molecules were observed not only at the water/PEO interface, but also within the
      PEO film. It indicates that the PEO and water form an ordered hydrogen-bonded
      network extending from the bulk PEO film into liquid water, which can provide an
      energy barrier for protein adsorption. Upon exposure to the protein solution, the
      SFG spectra of water at the water/PEO interface remained nearly unperturbed. For
      comparison, the SFG spectra of water/silica and water/polystyrene interfaces were
      also studied with and without HSA in the solution. The SFG spectra of the
      interfacial water were correlated with the amount of protein adsorbed on the
      surfaces using fluorescence microscopy, which showed that the amount of protein
      adsorbed on the PEO film was about 10 times less than that on a polystyrene film
      and 3 times less than that on silica.

PMID- 22390194
TI  - Electron and spin-density analysis of tirapazamine reduction chemistry.
AB  - Tirapazamine (TPZ, 1, 3-amino-1,2,4-benzotriazine 1,4-N,N-dioxide), the radical
      anion 2 formed by one-electron reduction of 1, and neutral radicals 3 and 4
      formed by protonation of 2 at O(N4) or O(N1), respectively, and their N-OH
      homolyses 3 -> 5 + .OH and 4 -> 6 + .OH have been studied with configuration
      interaction theory, perturbation theory, and density functional theory. A
      comprehensive comparative analysis is presented of structures and electronic
      structures and with focus on the development of an understanding of the spin
      density distributions of the radical species. The skeletons of radicals 3 and 4
      are distinctly nonplanar, several stereoisomeric structures are discussed, and
      there exists an intrinsic preference for 3 over 4. The N-oxides 1, 5, and 6 have
      closed-shell singlet ground states and low-lying, singlet biradical (SP-1, SP-6)
      or biradicaloid (SP-5) excited states. The doublet radicals 2, 3, and 4 are
      heavily spin-polarized. Most of the spin density of the doublet radicals 2, 3,
      and 4 is located in one (N,O)-region, and in particular, 3 and 4 are not C3
      centered radicals. Significant amounts of spin density occur in both rings in the
      singlet biradical(oid) excited states of 1, 5, and 6. The dipole moment of the N2
      C3(X) bond is large, and the nature of X provides a powerful handle to modulate
      the N2-C3 bond polarity with opposite effects on the two NO regions. Our studies
      show very low proton affinities of radical anion 2 and suggest that the pK(a) of
      radical [2+H] might be lower than 6. Implications are discussed regarding the
      formation of hydroxyl from 3 and/or 4, regarding the ability of 5 and 6 to react
      with carbon-centered radicals in a manner that ultimately leads to oxygen
      transfer, and regarding the interpretation of the EPR spectra of reduced TPZ
      species and of their spin-trap adducts.

PMID- 22390195
TI  - Diastereoselective aldol reaction of zincated 3-chloro-3-methyl-1-azaallylic
      anions as key step in the synthesis of 1,2,3,4-tetrasubstituted 3
      chloroazetidines.
AB  - Zincated 3-chloro-3-methyl-1-azaallylic anions undergo a stereoselective aldol
      addition across aromatic aldehydes and subsequent mesylation to produce syn alpha
      chloro-beta-mesyloxyketimines, which were isolated in 80-84% yield and high
      diastereomeric excess (dr > 97/3) after purification via flash chromatography.
      The syn alpha-chloro-beta-mesyloxyketimines were further stereoselectively
      reduced to give stereochemically defined 3-aminopropyl mesylates, which were
      cyclized to 1,2,3,4-tetrasubstituted 3-chloroazetidines containing three
      contiguous stereogenic centers. DFT calculations on the key aldol addition
      revealed the presence of a highly ordered bimetallic six-membered twist-boat-like
      transition state structure with a tetra-coordinated metal cyclic structure. DFT
      calculations revealed that chelation of both zinc and lithium cations in the
      transition state structure leads to the experimentally observed high syn
      diastereoselectivity of aldol reactions.

PMID- 22390196
TI  - The risk factors of CVA in Jordan.
AB  - This study aimed to identify the main risk factors of cerebrovascular accident
      (CVA) in Jordan. Identification of risk factors may help to reduce the incidence
      of CVA. A form was prepared for data collection which consisted of two parts to
      gather biodata and the incidence of risk factors. A sample of 200 patients with
      CVA (60% men) were randomly selected from various areas of Jordan. An age, region
      distribution, and gender-matched sample were selected to serve as control.
      Hypertension in the experimental group (66%) was significantly higher than the
      control group (32%) p  <  0.001. Half of the subjects with stroke had diabetes
      compared to 22% of the control group (p  <  0.001). Cardiovascular diseases were
      found in 29% of subjects with CVA compared to 14% in the control group (p  < 
      0.001). About 27% of the CVA group had hyperlipidemia in comparison to 13% in the
      controls (p <  0.002). Smokers represented 54% of the experimental group compared
      to 30% of the control group (p <  0.05). An important finding in the present
      study was that about half of the selected subjects with strokes were under the
      age of 60 years. In conclusion, hypertension, diabetes, cardiovascular diseases,
      hyperlipidemia, and smoking are risk factors for CVA in Jordan.

PMID- 22390197
TI  - Development of standard practice guidelines for open and closed system
      suctioning.
AB  - AIMS: This study was carried out to determine the knowledge and practice of
      nurses before and after training and the development of standard practice
      guidelines for open and closed system suctioning methods in patients with
      endotracheal tubes. BACKGROUND: Many life-threatening complications can occur
      when a suctioning procedure is not performed with the correct technique. It has
      been reported that standard practice guidelines for suctioning are insufficient
      in clinical practice. DESIGN: Non-participant structured observational study.
      METHODS: We assessed a total of 48 nurses who were employed in the cardiovascular
      surgery intensive care unit of a state hospital in Turkey. We used a
      questionnaire and nurse observation forms to assess the use of the open and
      closed system suctioning. RESULTS: There was a significant difference between the
      mean scores of the answers ('true', 'wrong' and 'I do not know') for the use of
      open and closed system suctioning before and after training. In addition, all
      steps of both suctioning procedures were carried out correctly during the third
      observation. CONCLUSIONS: The compliance of the nurses to the standard practice
      guidelines for open and closed suctioning and their knowledge levels on the
      subject were increased after training, while the implementation of standards was
      satisfactory. RELEVANCE TO CLINICAL PRACTICE: The development of open and closed
      system suctioning standard practice guidelines directly contributed to the
      enhancement of patient safety and the quality of nursing care. It is suggested
      that, as in other nursing care practices, suctioning should be carried out in
      accordance with standard practice guidelines, and health institutions should
      develop their standard practice guidelines and work in accordance with them.

PMID- 22390199
TI  - Hydrogenase: the next antibiotic target?
AB  - The struggle to control infectious diseases has become increasingly difficult due
      to resistance to current antibiotics and the co-existence of multiplying and non
      multiplying bacteria, which makes it an urgent task to discover new antibiotic
      targets and to develop new antibiotics. Hydrogenases are found in micro-organisms
      belonging to the archaea and bacteria domains, which can catalyse the reversible
      oxidation of hydrogen gas (H2<->2H+ +2e) and play pleiotropic roles in microbial
      survival. Studies have shown that H2 is a potent antioxidant and can selectively
      neutralize OH* (hydroxyl radicals). OH*, however, has been implicated as one of
      the mechanisms whereby bactericidal antibiotics and professional phagocytes kill
      bacteria. Thus we have enough reason to speculate that hydrogenases and H2 are
      conducive to increasing the virulence and antibiotic resistance of bacteria, and
      hydrogenase inhibitors would help control bacterial infection.

PMID- 22390200
TI  - Detection of Rickettsia spp. and host and habitat associations of fleas
      (Siphonaptera) in eastern Taiwan.
AB  - Rickettsia typhi and Rickettsia felis (Rickettsiales: Rickettsiaceae) are two
      rickettsiae principally transmitted by fleas, but the detection of either
      pathogen has rarely been attempted in Taiwan. Of 2048 small mammals trapped in
      eastern Taiwan, Apodemus agrarius Pallas (24.5%) and Mus caroli Bonhote (24.4%)
      (both: Rodentia: Muridae) were the most abundant, and M. caroli hosted the
      highest proportion of fleas (63.9% of 330 fleas). Two flea species were
      identified: Stivalius aporus Jordan and Rothschild (Siphonaptera: Stivaliidae),
      and Acropsylla episema Rothschild (Siphonaptera: Leptopsyllidae). Nested
      polymerase chain reaction targeting parts of the ompB and gltA genes showed six
      fleas to be positive for Rickettsia spp. (3.8% of 160 samples), which showed the
      greatest similarity to R. felis, Rickettsia japonica, Rickettsia conorii or
      Rickettsia sp. TwKM01. Rickettsia typhi was not detected in the fleas and
      Rickettsia co-infection did not occur. Both flea species were more abundant
      during months with lower temperatures and less rainfall, and flea abundance on M.
      caroli was not related to soil hardness, vegetative height, ground cover by
      litter or by understory layer, or the abundance of M. caroli. Our study reveals
      the potential circulation of R. felis and other rickettsiae in eastern Taiwan,
      necessitating further surveillance of rickettsial diseases in this region. This
      is especially important because many novel rickettsioses are emerging worldwide.

PMID- 22390198
TI  - AMP-activated protein kinase, stress responses and cardiovascular diseases.
AB  - AMPK (AMP-activated protein kinase) is one of the key players in maintaining
      intracellular homoeostasis. AMPK is well known as an energy sensor and can be
      activated by increased intracellular AMP levels. Generally, the activation of
      AMPK turns on catabolic pathways that generate ATP, while inhibiting cell
      proliferation and biosynthetic processes that consume ATP. In recent years,
      intensive investigations on the regulation and the function of AMPK indicates
      that AMPK not only functions as an intracellular energy sensor and regulator, but
      is also a general stress sensor that is important in maintaining intracellular
      homoeostasis during many kinds of stress challenges. In the present paper, we
      will review recent literature showing that AMPK functions far beyond its proposed
      energy sensor and regulator function. AMPK regulates ROS (reactive oxygen
      species)/redox balance, autophagy, cell proliferation, cell apoptosis, cellular
      polarity, mitochondrial function and genotoxic response, either directly or
      indirectly via numerous downstream pathways under physiological and pathological
      conditions.

PMID- 22390201
TI  - A quantitative review of ethnic group differences in experimental pain response:
      do biology, psychology, and culture matter?
AB  - OBJECTIVE: Pain is a subjectively complex and universal experience. We examine
      research investigating ethnic group differences in experimental pain response and
      factors contributing to group differences. METHOD: We conducted a systematic
      literature review and analysis of studies using experimental pain stimuli to
      assess pain sensitivity across multiple ethnic groups. Our search covered the
      period from 1944 to 2011, and used the PubMed bibliographic database; a reference
      source containing over 17 million citations. We calculated effect sizes;
      identified ethnic/racial group categories, pain stimuli, and measures; and
      examined findings regarding biopsychosociocultural factors contributing to
      ethnic/racial group differences. RESULTS: We found 472 studies investigating
      ethnic group differences and pain. Twenty-six of these met our review inclusion
      criteria of investigating ethnic group differences in experimental pain. The
      majority of studies included comparisons between African Americans (AA) and non
      Hispanic Whites (NHW). There were consistently moderate to large effect sizes for
      pain tolerance across multiple stimulus modalities; AA demonstrated lower pain
      tolerance. For pain threshold, findings were generally in the same direction, but
      effect sizes were small to moderate across ethnic groups. Limited data were
      available for suprathreshold pain ratings. A subset of studies comparing NHW and
      other ethnic groups showed a variable range of effect sizes for pain threshold
      and tolerance. CONCLUSION: There are potentially important ethnic/racial group
      differences in experimental pain perception. Elucidating ethnic group differences
      has translational merit for culturally competent clinical care and for addressing
      and reducing pain treatment disparities among ethnically/racially diverse groups.

PMID- 22390202
TI  - Ex vivo expansion of human Tregs by rabbit ATG is dependent on intact STAT3
      signaling in CD4+ T cells and requires the presence of monocytes.
AB  - The addition of low, nondepleting doses of rabbit antithymocyte globulin (ATG) to
      human peripheral blood mononuclear cells has been shown to expand functional
      CD4(+) CD25(+) FoxP3(+) regulatory T cells (Tregs) in vitro. This report is the
      first to elucidate the exact cellular mechanisms of ATG-mediated Treg expansion.
      CD4(+) T cells require monocytes, but not other antigen presenting cell subsets,
      to be present in coculture to expand Tregs. However, T cells do not require
      direct cell-cell contact with monocytes, suggesting the importance of soluble
      factors. Moreover, ATG initially "reprograms" CD4(+) T cells, but not monocytes,
      and induces STAT3 and STAT5 signaling in CD4(+) cells. These reprogrammed CD4(+)
      T cells subsequently secrete GM-CSF and IL-10 only in case of intact STAT3
      signaling, which in turn promote the generation of tolerogenic CD14(+) CD11c(+)
      dendritic cells characterized by enhanced IL-10 and decreased IL-12 production.
      Treg expansion following ATG treatment is accompanied by enhanced gene expression
      of both GM-CSF and Bcl-2, but not TGF-beta, in peripheral blood mononuclear
      cells. These results demonstrate that ex vivo expansion of human Tregs by ATG is
      due to its ability to reprogram CD4(+) T cells in a STAT3-dependent but TGF-beta
      independent manner, leading to the generation of monocyte-derived dendritic cells
      with a tolerogenic cytokine profile.

PMID- 22390203
TI  - What do we know about chronic kidney disease in India: first report of the Indian
      CKD registry.
AB  - BACKGROUND: There are no national data on the magnitude and pattern of chronic
      kidney disease (CKD) in India. The Indian CKD Registry documents the
      demographics, etiological spectrum, practice patterns, variations and special
      characteristics. METHODS: Data was collected for this cross-sectional study in a
      standardized format according to predetermined criteria. Of the 52,273 adult
      patients, 35.5%, 27.9%, 25.6% and 11% patients came from South, North, West and
      East zones respectively. RESULTS: The mean age was 50.1 +/- 14.6 years, with M:F
      ratio of 70:30. Patients from North Zone were younger and those from the East
      Zone older. Diabetic nephropathy was the commonest cause (31%), followed by CKD
      of undetermined etiology (16%), chronic glomerulonephritis (14%) and hypertensive
      nephrosclerosis (13%). About 48% cases presented in Stage V; they were younger
      than those in Stages III-IV. Diabetic nephropathy patients were older, more
      likely to present in earlier stages of CKD and had a higher frequency of males;
      whereas those with CKD of unexplained etiology were younger, had more females and
      more frequently presented in Stage V. Patients in lower income groups had more
      advanced CKD at presentation. Patients presenting to public sector hospitals were
      poorer, younger, and more frequently had CKD of unknown etiology. CONCLUSIONS:
      This report confirms the emergence of diabetic nephropathy as the pre-eminent
      cause in India. Patients with CKD of unknown etiology are younger, poorer and
      more likely to present with advanced CKD. There were some geographic variations.

PMID- 22390204
TI  - A non-natural nucleoside with combined therapeutic and diagnostic activities
      against leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer,
      presenting with approximately 5,000 new cases each year in the United States. An
      interesting enzyme implicated in this disease is terminal deoxynucleotidyl
      transferase (TdT), a specialized DNA polymerase involved in V(D)J recombination.
      TdT is an excellent biomarker for ALL as it is overexpressed in ~90% of ALL
      patients, and these higher levels correlate with a poor prognosis. These
      collective features make TdT an attractive target to design new selective anti
      cancer agents against ALL. In this report, we evaluate the anti-leukemia
      activities of two non-natural nucleotides designated 5-nitroindolyl-2'
      deoxynucleoside triphosphate (5-NITP) and 3-ethynyl-5-nitroindolyl-2'
      deoxynucleoside triphosphate (3-Eth-5-NITP). Using purified TdT, we demonstrate
      that both non-natural nucleotides are efficiently utilized as TdT substrates.
      However, 3-Eth-5-NITP is poorly elongated, and this observation validates its
      activity as a chain-terminator for blunt-end DNA synthesis. Cell-based
      experiments validate that the corresponding non-natural nucleoside produces
      robust cytostatic and cytotoxic effects against leukemia cells that overexpress
      TdT. The strategic placement of the ethynyl moiety allows the incorporated
      nucleoside triphosphate to be selectively tagged with an azide-containing
      fluorophore via "click" chemistry. This reaction allows the extent of nucleotide
      incorporation to be quantified such that the anti-cancer effects of the
      corresponding non-natural nucleoside can be self-assessed. The applications of
      this novel nucleoside are discussed, focusing on its use as a "theranostic" agent
      that can improve the accuracy of dosing regimens and accelerate clinical
      decisions regarding therapeutic intervention.

PMID- 22390205
TI  - Effect of mesoscopic fillers on the polymerization induced viscoelastic phase
      separation at near- and off-critical compositions.
AB  - We have investigated the effect of mesoscopic fillers on the polymerization
      induced viscoelastic phase separation of thermoplastic modified thermosets at
      near- and off-critical concentrations using optical microscopy, time-resolved
      light scattering, dynamic mechanical analyses, and rheological instrument.
      Mesoscopic fillers including sepiolite and nanosized silica showed a significant
      enhancement effect in viscoelastic phase separation, and resulted in pronounced
      differences in the phase structures at all concentrations of polyetherimide
      modified epoxy resins with dynamic asymmetry. For blends near critical
      concentration, the introduction of fillers led to much finer phase structure with
      smaller characteristic length scale. At off-critical composition (i.e., blends
      with low concentration of slow dynamic component), the strong polymer chain
      entanglement resulted in enwrapped mesoscopic fillers within a slow dynamic
      phase. The rheological behavior of the blends clearly demonstrated the
      significant enhancement effect of mesoscopic fillers in the viscoelastic phase
      separation. The apparent activation energy of polymer chain mobility obtained
      from dynamic mechanical study of glass transition reflected strong wrapping
      behavior of polymer chains on mesoscopic fillers, which were consistent with the
      rheological and light scattering study.

PMID- 22390206
TI  - Comparison of adherence between twice- and thrice-daily regimens of oral
      amoxicillin/clavulanic acid.
AB  - BACKGROUND AND OBJECTIVE: Few studies have analysed adherence with antibiotic
      treatment in patients with respiratory tract infections. The aim of this study
      was to compare the compliance of patients taking a pharmacokinetically enhanced
      formulation of amoxicillin/clavulanic acid twice daily with that of patients
      taking the standard formulation thrice daily. METHODS: Patients with suspected
      bacterial lower respiratory tract infections, pharyngitis and dental infections
      were included. Adherence was assessed by electronic monitoring, which recorded
      every opening of the patient's bottle of pills. The outcome variables were
      compliance with taking the medication, taking the correct dose and with timing of
      the dose. RESULTS: A total of 240 patients were enrolled (167 in the thrice-daily
      group and 73 in the twice-daily group). The percentage of doses taken was greater
      with the twice-daily regimen (84.5 +/- 22.8%) than with the thrice-daily regimen
      (72.7 +/- 20.1%; P < 0.001). Forty patients in the twice-daily group opened the
      container every 12 +/- 6 h during at least 80% of the course (54.8%), while only
      19.6% of the patients assigned to the thrice-daily formulation did so every 8 +/-
      4 h (P < 0.001). The percentage of patients who opened the container a
      satisfactory number of times per day was significantly higher among those taking
      the twice-daily regimen on days three, four, five, six and seven. Moreover, the
      thrice-daily group more frequently forgot to take the afternoon dose.
      CONCLUSIONS: The rate of compliance with amoxicillin/clavulanic acid therapy was
      very low. However, compliance with the new formulation that is taken twice-daily
      was significantly better.

PMID- 22390207
TI  - Ficaria verna Huds. extracts and their beta-cyclodextrin supramolecular systems.
AB  - BACKGROUND: Obtaining new pharmaceutical materials with enhanced properties by
      using natural compounds and environment-friendly methods is a continuous goal for
      scientists. Ficaria verna Huds. is a widespread perennial plant with applications
      in the treat of haemorrhoids and to cure piles; it has also anti-inflammatory,
      astringent, and antibiotic properties. The goal of the present study is the
      obtaining and characterization of new F. verna extract/beta-cyclodextrin
      complexes by using only natural compounds, solvents, and environment-friendly
      methods in order to increase the quality and acceptability versus toxicity
      indicator. Thus, the flavonoid content (as quercetin) of Ficaria verna Huds.
      flowers and leaves from the West side of Romania was determined and correlated
      with their antioxidant activity. Further, the possibility of obtaining beta
      cyclodextrin supramolecular systems was studied. RESULTS: F. verna flowers and
      leaves extracts were obtained by semi-continuous solid-liquid extraction. The raw
      concentrated extract was spectrophotometrically analyzed in order to quantify the
      flavonoids from plant parts and to evaluate the antioxidant activity of these
      extracts. The F. verna extracts were used for obtaining beta-cyclodextrin
      complexes; these were analyzed by scanning electron microscopy and Karl Fischer
      water titration; spectrophotometry was used in order to quantifying the
      flavonoids and evaluates the antioxidant activity. A higher concentration of
      flavonoids of 0.5% was determined in complexes obtained by crystallisation
      method, while only a half of this value was calculated for kneading method. The
      antioxidant activity of these complexes was correlated with the flavonoid content
      and this parameter reveals possible controlled release properties. CONCLUSIONS:
      The flavonoid content of F. verna Huds. from the West side of Romania (Banat
      county) is approximately the same in flowers and leaves, being situated at a
      medium value among other studies. beta-Cyclodextrin complexes of F. verna
      extracts are obtained with lower yields by crystallisation than kneading methods,
      but the flavonoids (as quercetin) are better encapsulated in the first case most
      probably due to the possibility to attain the host-guest equilibrium in the
      slower crystallisation process. F. verna extracts and their beta-cyclodextrin
      complexes have antioxidant activity even at very low concentrations and could be
      used in proper and valuable pharmaceutical formulations with enhanced
      bioactivity.

PMID- 22390208
TI  - Characteristics and smoking patterns of intermittent smokers.
AB  - Current models of smoking and dependence assume a need to smoke at regular
      intervals to maintain nicotine levels, yet about 25% of adult smokers do not
      smoke daily. This subset of intermittent smokers (ITS) has gone largely
      unexamined. In this study, we describe the demographics, smoking history, and
      smoking behavior of ITS (n = 282; 50.2% male) in comparison to daily smokers (DS;
      n = 233; 60.7% male). Within ITS, we also compare "converted" ITS (CITS), who had
      previously smoked daily, with "native" ITS (NITS). On average, ITS were 34.66
      years of age, and had smoked 42,850 cigarettes in the course of an average of 18
      years of smoking. They smoked an average of 4.38 days per week, consuming 4.39
      cigarettes a day on smoking days, and demonstrated considerable day-to-day
      variability in cigarette consumption. Almost half of ITS had Fagerstrom Test of
      Nicotine Dependence scores of 0, indicating no dependence. Compared to DS, ITS
      were more likely to cite alcohol drinking, socializing, and being with other
      smokers as common contexts for smoking, and they also more often cited being
      angry or stressed. Data suggested that ITS' behavior was not explained by use of
      other nicotine products nor by economic constraints on smoking, nor by
      differences in psychological adjustment. Within ITS, CITS were heavier, more
      frequent, and more dependent smokers. In many respects, CITS were intermediate
      between NITS and DS. ITS show distinct patterns of smoking behavior that are not
      well explained by current models of nicotine dependence.

PMID- 22390209
TI  - Using every tool in the toolbox.

PMID- 22390210
TI  - Reappraisal of the options for colorectal cancer screening in England.
AB  - AIM: The aim was to use newly available data to estimate the cost effectiveness
      and endoscopy requirements of screening options for colorectal cancer (CRC) to
      inform screening policy in England. METHODS: A state transition model simulated
      the life experience of a cohort of individuals in the general population of
      England with normal colon/rectal epithelium through to the development of
      adenomas and CRC and subsequent death. CRC natural history model parameters and
      screening test characteristics were estimated simultaneously by a process of
      model calibration. This process was fitted to observed data on CRC incidence in
      the absence of screening, data from existing screening programmes, and data from
      the UK flexible sigmoidoscopy (FS) screening trial. The costs, effects and
      resource impact were evaluated for a range of screening options involving the
      guaiac or immunochemical faecal occult blood test (gFOBT/iFOBT) and FS. RESULTS:
      The model suggests that screening strategies involving FS or iFOBT may produce
      additional benefits compared with the current policy of biennial gFOBT for 60-74
      year-olds. The age at which a single FS screen results in the greatest quality
      adjusted life year gain was 55, with similar gains for ages between 52 and 58.
      Strategies which combined FS and iFOBT showed further benefits and improved
      economic outcomes. CONCLUSIONS: Strategies which combine different screening
      modalities may provide greater clinical and economic benefits. The collection of
      comprehensive screening data using a uniform format will enable comparative
      analysis across screening programmes in different countries, will improve our
      understanding of the disease and will allow identification of optimal screening
      modalities.

PMID- 22390211
TI  - Beyond needs and expectations: identifying the barriers and facilitators to
      written medicine information provision and use in Australia.
AB  - PURPOSE: This study aimed to explore peoples' needs and expectations of written
      medicines information (WMI), and to determine the barriers and facilitators
      experienced or perceived in the context of WMI provision and use. METHODS: We
      conducted eight focus groups with 62 participants over 6 weeks in late 2008 in
      New South Wales, Australia. Using a semi-structured topic schedule and examples
      of WMI from Australia and other English-speaking countries as a guide, we
      explored themes relevant to WMI, including participant experiences, attitudes,
      beliefs and expectations. FINDINGS: Our findings suggest less than half had
      previously received WMI, with many unaware of its availability. Many, but not
      all, wanted WMI to supplement the spoken information they received but not to
      replace it, and it was predominantly used to facilitate informed choice,
      ascertain medicine suitability and review instructions. The current leaflets were
      considered technical and long, and a summary leaflet in addition to comprehensive
      information was favoured. Accurate side-effect information was the most important
      element that participants desired. The most common barriers to effective WMI use
      were time constraints and patient confidence, with participants citing
      empowerment, time and health-care professional (HCP)-patient relationships as
      important facilitators. CONCLUSION: The findings provide insight and
      understanding of peoples needs and expectations, and clarify issues associated
      with use and non-use of WMI. Challenges include addressing the barriers,
      especially of time and HCP attitudes to drive changes to workplace practices, and
      learning from the facilitating factors to encourage awareness and accessibility
      to WMI as a tool to empower patients.

PMID- 22390212
TI  - Expression of T-cell receptor-gammadelta in normal human skin, inflammatory
      dermatoses and mycosis fungoides.
AB  - BACKGROUND: T cells expressing the gammadelta T-cell receptor (TCR) (gammadelta T
      cells) are found in normal epithelial tissues such as the skin. However, the
      proportions of gammadelta T cells that may be observed in commonly encountered
      cutaneous diseases with a prominent lymphocytic infiltrate have not been
      elucidated. METHODS: Our pathology database was searched for cases of mycosis
      fungoides, erythema multiforme, graft-versus-host disease, lichen planus, lupus
      panniculitis and spongiotic dermatitis. Immunostaining for CD3, betaF1 and the
      TCR gamma chain was performed on formalin-fixed paraffin-embedded specimens
      retrieved from these cases to determine the normal range of gammadelta T cells in
      these diseases. RESULTS: In 100 of the 101 cases studied (99.0%), gammadelta T
      cells accounted for less than 10% of the T-cell infiltrate. Furthermore,
      gammadelta T cells were essentially absent in 74 cases (73.3%). CONCLUSIONS:
      These results suggest that gammadelta T cells very rarely account for more than
      10% of the lymphocytic infiltrate in common inflammatory or infiltrative
      processes of the skin. Any case of suspected mycosis fungoides or interface
      dermatitis that possesses more than 10% gammadelta T cells should raise
      consideration for further investigation.

PMID- 22390213
TI  - Total synthesis of (-)-kaitocephalin based on a Rh-catalyzed C-H amination.
AB  - A total synthesis of (-)-kaitocephalin, an ionotropic glutamate receptor
      antagonist, is accomplished in highly stereocontrolled manner via Overman
      rearrangement, rhodium-catalyzed benzylic C-H amination, pyrrolidine formation
      involving nucleophilic opening of a cyclic sulfamate, and rhodium-catalyzed
      allylic C-H amination as key steps.

PMID- 22390214
TI  - Applicability of DNA analysis on adhesive tape in forensic casework.
AB  - Adhesive tape is commonly used in crimes and is often the subject of forensic
      evaluation. DNA analysis of adhesive tape can provide DNA profiles of suspects.
      The object of this study was to evaluate the applicability of DNA analysis on
      adhesive tape samples in forensic casework. We retrospectively reviewed all cases
      involving adhesive tape or similar items received by our institute for DNA
      analysis during the past 11 years. From 100 forensic cases reviewed, 150 adhesive
      tape samples were examined. A total of 98 DNA profiles were obtained from these
      samples. Sixty-two of the profiles provided feasible case-relevant information.
      In conclusion, DNA profiling of adhesive tape samples can be useful in a variety
      of forensic cases.

PMID- 22390215
TI  - Analysis of veterinary drug residues in frog legs and other aquacultured species
      using liquid chromatography quadrupole time-of-flight mass spectrometry.
AB  - A liquid chromatography quadrupole time-of-flight (Q-TOF) mass spectrometry
      method was developed to analyze veterinary drug residues in frog legs and other
      aquacultured species. Samples were extracted using a procedure based on a method
      developed for the analysis of fluoroquinolones (FQs) in fish. Briefly, the tissue
      was extracted with dilute acetic acid and acetonitrile with added sodium
      chloride. After centrifugation, the extracts were evaporated and reconstituted in
      mobile phase. A molecular weight cutoff filter was used to clean up the final
      extract. A set of target compounds, including trimethoprim, sulfamethoxazole,
      chloramphenicol, quinolones, and FQs, was used to validate the method. Screening
      of residues was accomplished by collecting TOF (MS1) data and comparing the
      accurate mass and retention times of compounds to a database containing
      information for veterinary drugs. An evaluation of the MS data in fortified frog
      legs indicated that the target compounds could be consistently detected at the
      level of concern. The linearity and recoveries from matrix were evaluated for
      these analytes to estimate the amount of residue present. MS/MS data were also
      generated from precursor ions, and the mass accuracy of the product ions for each
      compound was compared to theoretical values. When the method was used to analyze
      imported frog legs, many of these residues were found in the samples, often in
      combination and at relatively high concentrations (>10 ng/g). The data from these
      samples were also evaluated for nontarget analytes such as residue metabolites
      and other chemotherapeutics.

PMID- 22390216
TI  - Cytochrome b5 increases cytochrome P450 3A4-mediated activation of anticancer
      drug ellipticine to 13-hydroxyellipticine whose covalent binding to DNA is
      elevated by sulfotransferases and N,O-acetyltransferases.
AB  - The antineoplastic alkaloid ellipticine is a prodrug, whose pharmacological
      efficiency is dependent on its cytochrome P450 (P450)- and/or peroxidase-mediated
      activation in target tissues. The P450 3A4 enzyme oxidizes ellipticine to five
      metabolites, mainly to 13-hydroxy- and 12-hydroxyellipticine, the metabolites
      responsible for the formation of ellipticine-13-ylium and ellipticine-12-ylium
      ions that generate covalent DNA adducts. Cytochrome b(5) alters the ratio of
      ellipticine metabolites formed by P450 3A4. While the amounts of the detoxication
      metabolites (7-hydroxy- and 9-hydroxyellipticine) were not changed with added
      cytochrome b(5), 12-hydroxy- and 13-hydroxyellipticine, and ellipticine N(2)
      oxide increased considerably. The P450 3A4-mediated oxidation of ellipticine was
      significantly changed only by holo-cytochrome b(5), while apo-cytochrome b(5)
      without heme or Mn-cytochrome b(5) had no such effect. The change in amounts of
      metabolites resulted in an increased formation of covalent ellipticine-DNA
      adducts, one of the DNA-damaging mechanisms of ellipticine antitumor action. The
      amounts of 13-hydroxy- and 12-hydroxyellipticine formed by P450 3A4 were similar,
      but more than 7-fold higher levels of the adduct were formed by 13
      hydroxyellipticine than by 12-hydroxyellipticine. The higher susceptibility of 13
      hydroxyellipticine toward heterolytic dissociation to ellipticine-13-ylium in
      comparison to dissociation of 12-hydroxyellipticine to ellipticine-12-ylium,
      determined by quantum chemical calculations, explains this phenomenon. The
      amounts of the 13-hydroxyellipticine-derived DNA adduct significantly increased
      upon reaction of 13-hydroxyellipticine with either 3'-phosphoadenosine-5'
      phosphosulfate or acetyl-CoA catalyzed by human sulfotransferases 1A1, 1A2, 1A3,
      and 2A1, or N,O-acetyltransferases 1 and 2. The calculated reaction free energies
      of heterolysis of the sulfate and acetate esters are by 10-17 kcal/mol more
      favorable than the energy of hydrolysis of 13-hydroxyellipticine, which could
      explain the experimental data.

PMID- 22390217
TI  - Men and women have specific needs that facilitate enrollment in HIV-prevention
      counseling.
AB  - Although reducing HIV risk is a primary motive for the design of HIV prevention
      interventions, the goals of the clients may be very different. Social theories of
      gender suggest that women, who often seek to resolve social and relational
      problems, may see HIV-prevention counseling as a mean of resolving partner
      violence. In contrast, men, who often worry about their physical strength, may
      seek to enroll in HIV-prevention programs when they experience physical symptoms
      unrelated to HIV. An unobtrusive study was conducted to observe enrollment in HIV
      risk-reduction counseling after measuring partner-violence complaints (e.g.,
      feeling threatened or being hit), emotional complaints (e.g., fatigue or
      anxiety), and physical complaints (e.g., cardiovascular or digestive symptoms).
      The sample was a group of 350 participants, 70% clients from a state-health
      department in North Central Florida and 30% community members. Consistent with
      predictions, complaints of partner violence had a positive association with
      enrollment in women but not in men, whereas complaints about physical health had
      a positive association with enrollment in men, but not in women. Emotional
      complaints did not predict enrollment in either gender group. This study suggests
      that broad, gender-specific population needs must be competently addressed within
      HIV-prevention programs and may be strategically used to increase program
      enrollment.

PMID- 22390219
TI  - Levofloxacin-induced delirium: is it a dangerous drug in patients with renal
      dysfunction?
AB  - The central nervous system (CNS) toxicity of fluoroquinolones is well known but
      usually occurs benign. In the literature, there are a few number of severe CNS
      toxicity cases related to fluoroquinolones. Levofloxacin is a third-generation
      fluorinated quinolone antibiotic, is the active levo stereoisomer of ofloxacin,
      and has one of the most favorable adverse reaction profiles. We describe a case
      of delirium associated with levofloxacin in a 55-year-old man who was
      hospitalized in our medical clinic for pneumonia.

PMID- 22390218
TI  - Patient adherence to and tolerability of self-administered interferon beta-1a
      using an electronic autoinjection device: a multicentre, open-label, phase IV
      study.
AB  - BACKGROUND: Achieving good adherence to self-injected treatments for multiple
      sclerosis can be difficult. Injection devices may help to overcome some of the
      injection-related barriers to adherence that can be experienced by patients. We
      sought to assess short-term adherence to, and tolerability of, interferon (IFN)
      beta-1a administered via electronic autoinjection device in patients with
      relapsing-remitting multiple sclerosis (RRMS). METHODS: BRIDGE (RebiSmart to self
      inject Rebif serum-free formulation in a multidose cartridge) was a 12-week,
      multicentre, open-label, single-arm, observational, Phase IV study in which
      patients self-administered IFN beta-1a (titrated to 44 MUg), subcutaneously (sc),
      three times weekly, via electronic autoinjection device. Patients were assessed
      at baseline and 4-weekly intervals to Week 12 or early termination (ET) for:
      physical examinations; diary card completion (baseline, Weeks 4, 8 only);
      neurological examinations (baseline, Week 12/ET only); MS Treatment Concern
      Questionnaire (MSTCQ; Weeks 4, 8, 12 only); Convenience Questionnaire (Week 12
      only); Hospital Anxiety and Depression Scale (HADS); and Paced Auditory Serial
      Addition Task (PASAT; baseline only). Adherence was defined as administration of
      >= 80% of scheduled injections, recorded by the autoinjection device. RESULTS:
      Overall, 88.2% (105/119; intent-to-treat population) of patients were adherent;
      67.2% (80/119) administered all scheduled injections. Medical reasons accounted
      for 35.6% (31/87) of missed injections, forgetfulness for 20.6% (18/87).
      Adherence did not correlate with baseline Expanded Disability Status Scale (P =
      0.821) or PASAT (P = 0.952) scores, or pre-study therapy (P = 0.303). No
      significant changes (baseline-Week 12) in mean HADS depression (P = 0.482) or
      anxiety (P = 0.156) scores were observed. 'Overall convenience' was the most
      important reported benefit of the autoinjection device. Device features
      associated with handling and ease of use were highly rated. Mean MSTCQ scores for
      'flu-like' symptoms (P = 0.022) and global side effects (P = 0.002) significantly
      improved from Week 4-12. Mean MSTCQ scores for pain at injection site and
      injection pain increased from Week 4-12 (P < 0.001). Adverse events were
      mild/moderate. No new safety signals were identified. CONCLUSION: Convenience and
      ease of use of the autoinjection device may improve adherence and, therefore,
      outcomes, in patients with RRMS receiving sc IFN beta-1a. TRIAL REGISTRATION: EU
      Clinical Trials Register (EU-CTR; http://www.clinicaltrialsregister.eu): 2009
      013333-24.

PMID- 22390220
TI  - Laparoscopic extraperitoneal colostomy in elective abdominoperineal resection for
      cancer: a single surgeon experience.
AB  - AIM: Parastomal herniation of end colostomies can be chronically debilitating for
      patients and a difficult problem to treat. To prevent parastomal hernia (PSH)
      formation an extraperitoneal colostomy (EPC) approach has been developed in open
      colorectal surgery and some studies have suggested a potential advantage to this
      approach. Here we describe our technique of laparoscopic extraperitoneal stoma
      formation and present our experience to date. METHODS: We performed a
      retrospective analysis of consecutive patients undergoing a laparoscopic
      abdominoperineal resection between March 1999 and March 2011. We performed the
      EPC technique as follows: under laparoscopic guidance, a smooth tip instrument
      was used to gently separate the peritoneum from the posterior aponeurotic plane
      to create an extraperitoneal tunnel running from the skin incision to the left
      flank of the abdominal cavity to join the previously dissected paracolic gutter.
      The colon was exteriorized and the position was checked to ensure the absence of
      torsion or kinking. RESULTS: Twenty-two patients underwent a standard
      laparoscopic abdominoperineal resection with total mesorectal excision. Colostomy
      was constructed extraperitoneally (EPC) or transperitoneally (TPC) in 12 and 10
      patients respectively. There were five complications requiring operative
      intervention: two stomal necrosis and one surgical site infection in the TPC
      group and two small bowel occlusions in the EPC group. Four patients from the TPC
      group developed PSH at 24, 36, 48 and 72 months respectively while there were no
      cases of PSH in the EPC group. CONCLUSION: Extraperitoneal laparoscopic colostomy
      showed a potential reduction of PSH in our series of patients.

PMID- 22390221
TI  - Causes of death in Tonga: quality of certification and implications for
      statistics.
AB  - BACKGROUND: Detailed cause of death data by age group and sex are critical to
      identify key public health issues and target interventions appropriately. In this
      study the quality of local routinely collected cause of death data from medical
      certification is reviewed, and a cause of death profile for Tonga based on
      amended data is presented. METHODS: Medical certificates of death for all deaths
      in Tonga for 2001 to 2008 and medical records for all deaths in the main island
      Tongatapu for 2008 were sought from the national hospital. Cause of death data
      for 2008 were reviewed for quality through (a) a review of current tabulation
      procedures and (b) a medical record review. Data from each medical record were
      extracted and provided to an independent medical doctor to assign cause of death,
      with underlying cause from the medical record tabulated against underlying cause
      from the medical certificate. Significant associations in reporting patterns were
      evaluated and final cause of death for each case in 2008 was assigned based on
      the best quality information from the medical certificate or medical record.
      Cause of death data from 2001 to 2007 were revised based on findings from the
      evaluation of certification of the 2008 data and added to the dataset.
      Proportional mortality was calculated and applied to age- and sex-specific
      mortality for all causes from 2001 to 2008. Cause of death was tabulated by age
      group and sex, and age-standardized (all ages) mortality rates for each sex by
      cause were calculated. RESULTS: Reported tabulations of cause of death in Tonga
      are of immediate cause, with ischemic heart disease and diabetes
      underrepresented. In the majority of cases the reported (immediate) cause fell
      within the same broad category as the underlying cause of death from the medical
      certificate. Underlying cause of death from the medical certificate, attributed
      to neoplasms, diabetes, and cardiovascular disease were assigned to other
      underlying causes by the medical record review in 70% to 77% of deaths. Of the 28
      (6.5%) deaths attributed to nonspecific or unknown causes on the medical
      certificate, 17 were able to be attributed elsewhere following review of the
      medical record. Final cause of death tabulations for 2001 to 2008 demonstrate
      that noncommunicable diseases are leading adult mortality, and age-standardized
      rates for cardiovascular diseases, neoplasms, and diabetes increased
      significantly between 2001 to 2004 and 2005 to 2008. Cause of death data for 2001
      to 2008 show increasing cause-specific mortality (deaths per 100,000) from 2001
      2004 to 2005-2008 from cardiovascular (194-382 to 423-644 in 2005-2008 for males
      and 108-227 to 194-321 for females) and other noncommunicable diseases that
      cannot be accounted for by changes in the age structure of the population.
      Mortality from diabetes for 2005 to 2008 is estimated at 94 to 222 deaths per
      100,000 population for males and 98 to 190 for females (based on the range of
      plausible all-cause mortality estimates) compared with 2008 estimates from the
      global burden of disease study of 40 (males) and 53 (females) deaths per 100,000
      population. DISCUSSION: Certification of death was generally found to be the most
      reliable data on cause of death in Tonga available for Tonga, with 93% of the
      final assigned causes following review of the 2008 data matching those listed on
      the medical certificate of death. Cause of death data available in Tonga can be
      improved by routinely tabulating data by underlying cause and ensuring
      contributory causes are not recorded in Part I of the certificate during data
      entry to the database. There is significantly more data on cause of death
      available in Tonga than are routinely reported or known to international
      agencies.

PMID- 22390223
TI  - Use of participatory research and photo-voice to support urban Aboriginal healthy
      eating.
AB  - The aim of this research was to work collaboratively with an urban Aboriginal
      community to understand meanings of food and food insecurity and strengthen
      responses to this issue. The project took place at the Wathaurong Aboriginal
      Cooperative in Geelong, South Eastern Australia in 2009-2010. Photo-voice
      research methods were used to explore meanings of food and food insecurity. This
      identified that food selections were influenced by family harmony, collectivism
      and satiation of hunger with cheap high carbohydrate and fat foods. People were
      also proud of their hunter-gatherer heritage and saw the Wathaurong Aboriginal
      Cooperative as leaders in healthy food provision. Action research cycles were
      used to develop responses including plates depicting healthy food portions,
      social cooking opportunities, development of a cooking television series and a
      specialised cook-book. The partnership required researchers to listen carefully
      to respond to needs of the Wathaurong Aboriginal Cooperative, and this meant
      adapting research plans to suit the local environment and community partner
      needs. There is potential for Aboriginal organisations to provide further
      leadership for healthy eating and food security through workplace food policies
      and partnerships with food security agencies. Use of Aboriginal nutrition
      knowledge to provide nutrition education may be useful in health promotion
      approaches.

PMID- 22390222
TI  - Reversible paraneoplastic encephalitis in three patients with ovarian neoplasms.
AB  - Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is a recently described
      potentially lethal but treatable disorder that often occurs as a paraneoplastic
      manifestation of ovarian teratomas. We report three women with this disorder who
      presented with subacute onset of delirium, seizures and autonomic instability.
      Anti-NMDA receptor antibodies were detectable in the serum or cerebrospinal fluid
      of each patient. Ovarian masses were detected in two patients, and subsequently
      excised. In the third patient, an empirical bilateral salpingo-oophorectomy was
      performed and revealed a microscopic neoplasm. All patients experienced slow
      reversal of the neurological symptoms following surgery and immunotherapy. Our
      experience suggests that prompt syndrome recognition followed by tumor removal
      and immunotherapy usually results in neurological recovery.

PMID- 22390224
TI  - Generation of indeno[1,2-c]pyrroles via a Pd-catalyzed reaction of 2
      alkynylbromobenzene with propargylic sulfonamide.
AB  - A novel route for the efficient assembly of indeno[1,2-c]pyrrole derivatives via
      a palladium-catalyzed tandem reaction of 2-alkynylbromobenzene with propargylic
      sulfonamide is reported. The starting materials are easily available, and the
      reaction proceeds smoothly with good functional group tolerance.

PMID- 22390226
TI  - Generational differences in young adults' life goals, concern for others, and
      civic orientation, 1966-2009.
AB  - Three studies examined generational differences in life goals, concern for
      others, and civic orientation among American high school seniors (Monitoring the
      Future; N = 463,753, 1976-2008) and entering college students (The American
      Freshman; N = 8.7 million, 1966-2009). Compared to Baby Boomers (born 1946-1961)
      at the same age, GenX'ers (born 1962-1981) and Millennials (born after 1982)
      considered goals related to extrinsic values (money, image, fame) more important
      and those related to intrinsic values (self-acceptance, affiliation, community)
      less important. Concern for others (e.g., empathy for outgroups, charity
      donations, the importance of having a job worthwhile to society) declined
      slightly. Community service rose but was also increasingly required for high
      school graduation over the same time period. Civic orientation (e.g., interest in
      social problems, political participation, trust in government, taking action to
      help the environment and save energy) declined an average of d = -.34, with about
      half the decline occurring between GenX and the Millennials. Some of the largest
      declines appeared in taking action to help the environment. In most cases,
      Millennials slowed, though did not reverse, trends toward reduced community
      feeling begun by GenX. The results generally support the "Generation Me" view of
      generational differences rather than the "Generation We" or no change views.

PMID- 22390225
TI  - The erosive effects of racism: reduced self-control mediates the relation between
      perceived racial discrimination and substance use in African American
      adolescents.
AB  - Perceived racial discrimination, self-control, anger, and either substance use or
      use cognitions were assessed in 2 studies conducted with samples of African
      American adolescents. The primary goal was to examine the relation between
      discrimination and self-control over time; a 2nd goal was to determine whether
      that relation mediates the link between discrimination and substance use found in
      previous research. Study 1, which included a latent growth curve analysis with 3
      waves of data, indicated that experience with discrimination (from age 10 years
      to age 18 years) was associated with reduced self-control, which then predicted
      increased substance use. Additional analyses indicated anger was also a mediator
      of this discrimination to use relation. Study 2, which was experimental, showed
      that envisioning an experience involving discrimination was associated with an
      increase in substance-related responses to double entendre words (e.g., pot,
      roach) in a word association task, especially for participants who were low in
      dispositional self-control. The effect was again mediated by reports of anger.
      Thus, the "double mediation" pattern was discrimination -> more anger and reduced
      self-control -> increased substance use and/or substance cognitions. Results are
      discussed in terms of the long-term impact of discrimination on self-control and
      health behavior. Implications for interventions aimed at ameliorating the
      negative effects of discrimination and low self-control on health are also
      discussed.

PMID- 22390227
TI  - Unseen disadvantage: how American universities' focus on independence undermines
      the academic performance of first-generation college students.
AB  - American universities increasingly admit first-generation college students whose
      parents do not have 4-year degrees. Once admitted, these students tend to
      struggle academically, compared with continuing-generation students--students who
      have at least 1 parent with a 4-year degree. We propose a cultural mismatch
      theory that identifies 1 important source of this social class achievement gap.
      Four studies test the hypothesis that first-generation students underperform
      because interdependent norms from their mostly working-class backgrounds
      constitute a mismatch with middle-class independent norms prevalent in
      universities. First, assessing university cultural norms, surveys of university
      administrators revealed that American universities focus primarily on norms of
      independence. Second, identifying the hypothesized cultural mismatch, a
      longitudinal survey revealed that universities' focus on independence does not
      match first-generation students' relatively interdependent motives for attending
      college and that this cultural mismatch is associated with lower grades. Finally,
      2 experiments at both private and public universities created a match or mismatch
      for first-generation students and examined the performance consequences. Together
      these studies revealed that representing the university culture in terms of
      independence (i.e., paving one's own paths) rendered academic tasks difficult
      and, thereby, undermined first-generation students' performance. Conversely,
      representing the university culture in terms of interdependence (i.e., being part
      of a community) reduced this sense of difficulty and eliminated the performance
      gap without adverse consequences for continuing-generation students. These
      studies address the urgent need to recognize cultural obstacles that contribute
      to the social class achievement gap and to develop interventions to address them.

PMID- 22390228
TI  - meso-Tetrakis(pentafluorophenyl)porphyrin-derived chromene-annulated chlorins.
AB  - The synthesis of mono- and bis-chromene-annulated meso
      (pentafluorophenyl)chlorins from meso-tetrakis(pentafluorophenyl)porphyrins by an
      OsO(4)-mediated dihydroxylation reaction, followed by an intramolecular
      nucleophilic aromatic substitution reaction, is described. The reaction sequence
      is applicable to the free base systems as well as their Zn(II), Ni(II), Pd(II),
      and Pt(II) complexes. The optical properties (UV-vis and fluorescence spectra) of
      the (metallo)chlorin-like chromophores that possess slightly red-shifted optical
      spectra compared to the corresponding 2,3-dihydroxychlorins are reported.
      Molecular modeling and (1)H-(19)F-HOESY NMR spectroscopy provide indications for
      the conformation of the chromene-annulated chromophores. Using (1)H-(1)H COSY and
      (19)F-(19)F QF-COSY NMR spectra, we interpret the (1)H and (19)F NMR spectra of
      the porphyrins and chlorins, thus providing a refined reference point for the use
      of (19)F NMR spectroscopy as a diagnostic tool in the analysis of meso
      pentafluorophenyl-substituted porphyrinoids.

PMID- 22390230
TI  - The use of solid supports to generate nucleic acid carriers.
AB  - Nucleic acids are the foundation stone of all cellular processes. Consequently,
      the use of DNA or RNA to treat genetic and acquired disorders (so called gene
      therapy) offers enormous potential benefits. The restitution of defective genes
      or the suppression of malignant genes could target a range of diseases, including
      cancers, inherited diseases (cystic fibrosis, muscular dystrophy, etc.), and
      viral infections. However, this strategy has a major barrier: the size and charge
      of nucleic acids largely restricts their transit into eukaryotic cells. Potential
      strategies to solve this problem include the use of a variety of natural and
      synthetic nucleic acid carriers. Driven by the aim and ambition of translating
      this promising therapeutic approach into the clinic, researchers have been
      actively developing advanced delivery systems for nucleic acids for more than 20
      years. A decade ago we began our investigations of solid-phase techniques to
      construct families of novel nucleic acid carriers for transfection. We envisaged
      that the solid-phase synthesis of polycationic dendrimers and derivatized
      polyamimes would offer distinct advantages over solution phase techniques.
      Notably in solid phase synthesis we could take advantage of mass action and
      streamlined purification procedures, while simplifying the handling of compounds
      with high polarities and plurality of functional groups. Parallel synthesis
      methods would also allow rapid access to libraries of compounds with improved
      purities and yields over comparable solution methodologies and facilitate the
      development of structure activity relationships. We also twisted the concept of
      the solid-phase support on its head: we devised miniaturized solid supports that
      provided an innovative cell delivery vehicle in their own right, carrying
      covalently conjugated cargos (biomolecules) into cells. In this Account, we
      summarize the main outcomes of this series of chemically related projects.

PMID- 22390229
TI  - Symptom recognition of heart attack and stroke in nine European countries: a
      representative survey.
AB  - BACKGROUND: Cardiovascular diseases are the number one cause of death and a
      source of chronic disability. OBJECTIVES: To assess recognition of and reaction
      to symptoms of heart attack and stroke, and how recognition is related to the
      frequency of consulting physicians and other information sources. DESIGN: Face-to
      face computer-assisted personal interviews. PARTICIPANTS: Representative sample
      of 10,228 persons in Austria, France, Germany, Italy, the Netherlands, Poland,
      Russia, Spain and UK, aged 14-98. MAIN OUTCOME VARIABLES: Recognition of heart
      attack and stroke symptoms and proper reaction to symptoms. RESULTS: Chest pain
      was the only heart attack symptom recognized by more than 50% of participants.
      Eight percent knew no symptoms. Of 14 stroke symptoms, none was recognized by
      more than 50% of participants; 19% could not identify any symptom. For both heart
      attack and stroke, Germans and Austrians recognized the largest number of
      symptoms. Persons in Italy, Poland, Russia and Spain knew only about half as many
      symptoms as in Germany or Austria. Only 51% of Europeans would call an ambulance
      when someone suffers a stroke, the fewest (33 and 34%) in Germany and Austria. In
      most countries, people who consulted their physician more frequently had no
      better recognition of heart attack or stroke symptoms. CONCLUSIONS: The majority
      of persons in nine European countries recognize few heart attack and stroke
      symptoms; many do not know how to react. This low level of knowledge constitutes
      a major health risk and likely leads to delay in treatment, contributing to the
      high mortality and morbidity from these diseases.

PMID- 22390231
TI  - Multivariable analyses of the relationships between age, gender, and body mass
      index and the source of chronic low back pain.
AB  - OBJECTIVE: To examine the combined relationships between age, gender, and body
      mass index (BMI) and the specific source of chronic low back pain. DESIGN:
      Retrospective chart review. SETTING: University spine center. PATIENTS: Charts
      from 378 cases from 358 consecutive patients were reviewed and 157 independent
      cases from 153 patients who underwent definitive diagnostic injections were
      analyzed. INTERVENTIONS: Discography, dual diagnostic facet joint blocks,
      sacroiliac joint injections, anesthetic interspinous ligaments/opposing spinous
      processes/posterior fusion hardware injections, percutaneous augmentation.
      OUTCOME MEASURES: Chronic low back pain source was the primary outcome variable.
      Predictor variables included age at initial presentation, gender, and BMI.
      RESULTS: Age, gender, and BMI were each significantly associated with the source
      of chronic low back pain, after controlling for the effects of each other.
      Increases in age were associated with significant decreases in the odds of
      internal disc disruption (IDD) vs facet joint pain (FJP), sacroiliac joint pain
      (SIJP), and other sources and decreases in the odds of FJP and SIJP vs other
      sources. Being female was associated with significant increases in the odds of
      SIJP vs IDD, FJP, and other sources. Increased BMI was associated with
      significant increases in the odds of FJP vs SIJP. CONCLUSIONS: These findings
      suggest a significant relationship among gender, age, and BMI and structural
      causes of chronic low back pain. Lumbar IDD is more prevalent in young males
      while FJP is more prevalent in females with increased BMI. Female gender and low
      BMI are associated with SIJP.

PMID- 22390232
TI  - Simulated IR, isotropic and anisotropic Raman, and vibrational circular dichroism
      amide I band profiles of stacked beta-sheets.
AB  - The amide I mode is a highly structure sensitive vibration of polypeptides that
      gives rise to a very strong band in IR absorption and a moderate band in Raman
      spectra. Many theoretical simulations of IR-band profiles have been undertaken
      thus far in order to expand the usability of amide I for the structure analysis
      of peptides and proteins. These simulations have thus far focused on the IR band
      profiles and to a limited extent on calculating the corresponding vibrational
      circular dichroism (VCD) signal. In this paper, we use excitonic coupling theory
      to simulate the IR, isotropic Raman, anisotropic Raman, and VCD band profiles of
      amide I of parallel and antiparallel beta-sheets as well as of two layers of
      stacked beta-sheets with antiparallel and parallel orientations of the respective
      sheets. Our calculations reveal anisotropic Raman and to a lesser extent VCD
      amide I profiles rather than the corresponding IR profile as suitable tools to
      discriminate between parallel and antiparallel beta-sheets. Stacking has a very
      limited influence on the Raman and IR band profiles, but enhance the VCD signal,
      the sign of which allows one to discriminate between parallel and antiparallel
      orientations of stacked sheets. Helical twisting and bending of parallel beta
      sheets give rise to a very enhanced positive couplet, in agreement with the
      recent work of Schweitzer-Stenner and Measey (J. Am. Chem. Soc., 2011, 133,
      1066). Stochastic uncorrelated inhomogeneity of individual peptide groups causes
      significant asymmetric broadening of Raman bands and, to a lesser extent, of IR
      bands and reduces the VCD-couplet of stacked beta-sheets.

PMID- 22390234
TI  - Trace rare earth element detection in food and agricultural products based on
      flow injection walnut shell packed microcolumn preconcentration coupled with
      inductively coupled plasma mass spectrometry.
AB  - With the extensive use of rare earth elements (REEs) in agriculture as fertilizer
      and feed additives, the concentration of REEs has increased in environmental and
      biological samples and finally impaired human health by food chain accumulation.
      The determination of trace REEs has gained considerable importance because of
      their toxicity and increasing occurrence. In this work, walnut shell has been
      used as the green adsorbent in online preconcentration and detection of REEs in
      food and agricultural products coupled with inductively coupled plasma mass
      spectrometry (ICP-MS). Because of the porous surface and abundant -COO(-) groups
      on the walnut shell surface, the walnut shell-packed microcolumn provides high
      adsorption efficiency and high tolerable capacity for coexisting ions. Under the
      optimized conditions, the adsorption efficiency of the walnut shell packed
      microcolumn was as high as 98.9% for 15 REEs, and the tolerable concentration
      ratios were between 2000 and 80,000,000 for 37 kinds of coexisting interfering
      ions. The enhancement factors achieved were 79-102 for 15 REEs with a sample
      loading volume of 4.7 mL. The detection limits were in the range of 2-34 pg g(
      1). The relative standard deviation for 11 replicate preconcentrations of 2.5 ng
      L(-1) REEs solution ranged from 0.5 to 2.0%. The present method was successfully
      applied to selective determination of REEs in 4 environmental and biological
      certified reference materials and 18 locally collected food and agricultural
      products.

PMID- 22390233
TI  - Type III bare lymphocyte syndrome associated with a novel RFXAP mutation: a case
      report.
AB  - Type III bare lymphocyte syndrome (BLS) is a severe combined immunodeficiency
      disease caused by the absence of MHC Class II expression associated with low
      expression of class I molecules. Here, we report a case with type III BLS who
      lacked RFXAP (Regulatory factor X-associated protein) expression as a result from
      a novel mutation introducing a premature stopcodon in DE-region at amino acid 73.

PMID- 22390235
TI  - Evaluation of 96 SNPs in 14 populations for worldwide individual identification.
AB  - Great advances have been made recently in searching for individual identification
      single-nucleotide polymorphisms (IISNPs or IDSNPs). Such SNPs as suggested by
      SNPforID scientists and by Pakstis et al., are promising, although they were
      selected from older or smaller databases rather than the most recent database.
      Here, we describe a new computational strategy for developing IDSNPs based on
      HapMap. We searched through HapMap r27 for SNPs having minor allele frequencies
      >=0.30 in all its 11 populations and found more than 1881 qualified SNPs. We
      examined 96 of them with 183 DNA samples from three Chinese populations using
      Illumina arrays. The average allele frequency for these 96 SNPs among the three
      populations was 0.495/0.505, the average number of identical SNP genotypes shared
      by two individuals among the 14 populations (three Chinese and 11 HapMap) was
      37.9, and the random matching probability for two unrelated Hans to match in all
      96 genotypes was 9.793 * 10(-39). Thus, most of these 96 SNPs are universally
      applicable.

PMID- 22390236
TI  - The technique of orthotopic mouse lung transplantation as a movie-improved
      learning by visualization.
AB  - The introduction of the mouse model of orthotopic single-lung transplantation has
      significantly advanced research in experimental lung transplantation.
      Technically, this model is demanding and presents major challenges to the
      researcher. In order to facilitate and accelerate the successful acquisition of
      this technique, we provide here a narrated movie in which the full
      transplantation procedure is comprehensively illustrated, featuring all key
      operative steps, but also highlighting potential pitfalls.

PMID- 22390237
TI  - Clock genes and clock-controlled genes in the regulation of metabolic rhythms.
AB  - Daily rotation of the Earth on its axis and yearly revolution around the Sun
      impose to living organisms adaptation to nyctohemeral and seasonal periodicity.
      Terrestrial life forms have developed endogenous molecular circadian clocks to
      synchronize their behavioral, biological, and metabolic rhythms to environmental
      cues, with the aim to perform at their best over a 24-h span. The coordinated
      circadian regulation of sleep/wake, rest/activity, fasting/feeding, and
      catabolic/anabolic cycles is crucial for optimal health. Circadian rhythms in
      gene expression synchronize biochemical processes and metabolic fluxes with the
      external environment, allowing the organism to function effectively in response
      to predictable physiological challenges. In mammals, this daily timekeeping is
      driven by the biological clocks of the circadian timing system, composed of
      master molecular oscillators within the suprachiasmatic nuclei of the
      hypothalamus, pacing self-sustained and cell-autonomous molecular oscillators in
      peripheral tissues through neural and humoral signals. Nutritional status is
      sensed by nuclear receptors and coreceptors, transcriptional regulatory proteins,
      and protein kinases, which synchronize metabolic gene expression and epigenetic
      modification, as well as energy production and expenditure, with behavioral and
      light-dark alternance. Physiological rhythmicity characterizes these biological
      processes and body functions, and multiple rhythms coexist presenting different
      phases, which may determine different ways of coordination among the circadian
      patterns, at both the cellular and whole-body levels. A complete loss of
      rhythmicity or a change of phase may alter the physiological array of rhythms,
      with the onset of chronodisruption or internal desynchronization, leading to
      metabolic derangement and disease, i.e., chronopathology.

PMID- 22390238
TI  - Expression of clock genes in human subcutaneous and visceral adipose tissues.
AB  - Disrupted circadian rhythms are associated with obesity and metabolic
      alterations, but little is known about the participation of peripheral circadian
      clock machinery in these processes. The aim of the present study was to analyze
      RNA expression of clock genes in subcutaneous (SAT) and visceral (VAT) adipose
      tissues of male and female subjects in AM (morning) and PM (afternoon) periods,
      and its interactions with body mass index (BMI). Ninety-one subjects (41 +/- 11
      yrs of age) presenting a wide range of BMI (21.4 to 48.6 kg/m(2)) were included.
      SAT and VAT biopsies were obtained from patients undergoing abdominal surgeries.
      Clock genes expressions were evaluated by qRT-PCR. The only clock gene that
      showed higher expression (p < .0001) in SAT in comparison to VAT was PER1 of
      female (372%) and male (326%) subjects. Different patterns of expression between
      the AM and PM periods were observed, in particular REV-ERBalpha, which was
      reduced (p < .05) at the PM period in SAT and VAT of both women and men (women:
      ~53% lower; men: ~78% lower), whereas CLOCK expression was not altered.
      Relationships between clock genes were different in SAT vs. VAT. BMI was
      negatively correlated with SATPER1 (r = -.549; p = .001) and SATPER2 (r = -.613;
      p = .0001) and positively with VATCLOCK (r = .541; p = .001) and VATBMAL1 (r =
      .468; p = .007) only in women. These data suggest that the circadian clock
      machinery of adipose tissue depots differs between female and male subjects, with
      a sex-specific effect observed for some genes. BMI correlated with clock genes,
      but at this moment it is not possible to establish the cause-effect relationship.

PMID- 22390239
TI  - Effects of dietary resveratrol on the sleep-wake cycle in the non-human primate
      gray mouse lemur (Microcebus murinus).
AB  - Converging evidence shows that the non-human primate gray mouse lemur (Microcebus
      murinus) is ideal for the study of the aging process and for testing the effects
      of new therapies and dietary interventions on age-associated pathologies. One
      such dietary supplement is resveratrol (RSV), a dietary polyphenolic compound
      with several positive effects on metabolic functions and longevity. However,
      little is known about the effect of RSV on the lemur sleep-wake cycle, which
      reflects mammalian brain function and health. In the present study, the authors
      investigated this effect by comparing sleep-wake cycles in adult lemurs based on
      electroencephalographic (EEG) rhythms. The effect of short-term RSV
      supplementation on the sleep-wake cycle of mouse lemurs was evaluated in
      entrained conditions (long-day photoperiods, light:dark 14:10). After 3 wks of
      RSV supplementation, the animals exhibited a significantly increased proportion
      of active-wake time, occurring mainly during the resting phase of the sleep-wake
      cycle (+163%). The increase in active-wake time with RSV supplementation was
      accompanied by a significant reduction of both paradoxical sleep (-95%) and slow
      wave sleep (-38%). These changes mainly occurred during the resting phase of the
      sleep-wake cycle (RSV supplementation induced negligible changes in active-wake
      time during the active phase of the sleep-wake cycle). The present data suggest
      that RSV may be a potent regulator of sleep-wake rhythms and could be of major
      interest in the study of sleep perturbations associated with aging and
      neuropathology.

PMID- 22390240
TI  - Diurnal variation in vascular function: role of sleep.
AB  - Although vascular function is lower in the morning than afternoon, previous
      studies have not assessed the influence of prior sleep on this diurnal variation.
      The authors employed a semiconstant routine protocol to study the contribution of
      prior nocturnal sleep to the previously observed impairment in vascular function
      in the morning. Brachial artery vascular function was assessed using the flow
      mediated dilation technique (FMD) in 9 healthy, physically active males (mean +/-
      SD: 27 +/- 9 yrs of age), at 08:00 and 16:00 h following, respectively, 3.29 +/-
      .37 and 3.24 +/- .57 h prior sleep estimated using actimetry. Heart rate and
      systolic and diastolic blood pressures were also measured. The data of the
      experimental sleep condition were compared with the data of the "normal" diurnal
      sleep condition, in which FMD measurements were obtained from 21 healthy
      individuals who slept only during the night, as usual, before the morning test
      session. The morning-afternoon difference in FMD was 1 +/- 4% in the experimental
      sleep condition compared with 3 +/- 4% in the normal sleep condition (p = .04).
      This difference was explained by FMD being 3 +/- 3% lower in afternoon following
      the prior experimental sleep (p = .01). These data suggest that FMD is more
      dependent on the influence of supine sleep than the endogenous circadian
      timekeeper, in agreement with our previous finding that diurnal variation in FMD
      is influenced by exercise. These findings also raise the possibility of a lower
      homeostatic "set point" for vascular function following a period of sleep and in
      the absence of perturbing hemodynamic fluctuation.

PMID- 22390241
TI  - Young women with major depression live on higher homeostatic sleep pressure than
      healthy controls.
AB  - There is mounting evidence for the involvement of the sleep-wake cycle and the
      circadian system in the pathogenesis of major depression. However, only a few
      studies so far focused on sleep and circadian rhythms under controlled
      experimental conditions. Thus, it remains unclear whether homeostatic sleep
      pressure or circadian rhythms, or both, are altered in depression. Here, the
      authors aimed at quantifying homeostatic and circadian sleep-wake regulatory
      mechanisms in young women suffering from major depressive disorder and healthy
      controls during a multiple nap paradigm under constant routine conditions. After
      an 8-h baseline night, 9 depressed women, 8 healthy young women, and 8 healthy
      older women underwent a 40-h multiple nap protocol (10 short sleep-wake cycles)
      followed by an 8-h recovery night. Polysomnographic recordings were done
      continuously, and subjective sleepiness was assessed. In order to measure
      circadian output, salivary melatonin samples were collected during scheduled
      wakefulness, and the circadian modulation of sleep spindles was analyzed with
      reference to the timing of melatonin secretion. Sleep parameters as well as non
      rapid eye movement (NREM) sleep electroencephalographic (EEG) spectra were
      determined for collapsed left, central, and right frontal, central, parietal, and
      occipital derivations for the night and nap-sleep episodes in the frequency range
      .75-25 Hz. Young depressed women showed higher frontal EEG delta activity, as a
      marker of homeostatic sleep pressure, compared to healthy young and older women
      across both night sleep episodes together with significantly higher subjective
      sleepiness. Higher delta sleep EEG activity in the naps during the biological day
      were observed in young depressed women along with reduced nighttime melatonin
      secretion as compared to healthy young volunteers. The circadian modulation of
      sleep spindles between the biological night and day was virtually absent in
      healthy older women and partially impaired in young depressed women. These data
      provide strong evidence for higher homeostatic sleep pressure in young moderately
      depressed women, along with some indications for impairment of the strength of
      the endogenous circadian output signal involved in sleep-wake regulation. This
      finding may have important repercussions on the treatment of the illness as such
      that a selective suppression of EEG slow-wave activity could promote acute mood
      improvement.

PMID- 22390242
TI  - Relationship of chronotype to sleep, light exposure, and work-related fatigue in
      student workers.
AB  - Students who work during the school year face the potential of sleep deprivation
      and its effects, since they have to juggle between school and work
      responsibilities along with social life. This may leave them with less time left
      for sleep than their nonworking counterparts. Chronotype is a factor that may
      exert an influence on the sleep of student workers. Also, light and social
      zeitgebers may have an impact on the sleep-related problems of this population.
      This study aimed to document sleep, light exposure patterns, social rhythms, and
      work-related fatigue of student workers aged 19-21 yrs and explore possible
      associations with chronotype. A total of 88 student workers (mean +/- SD: 20.18
      +/- .44 yrs of age; 36 males/52 females) wore an actigraph (Actiwatch-L; Mini
      Mitter/Respironics,Bend, OR) and filled out the Social Rhythm Metric for two
      consecutive weeks during the school year. Also, they completed the Morningness
      Eveningness Questionnaire (MEQ), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep
      Quality Index (PSQI), and Occupational Fatigue Exhaustion/Recovery Scale (OFER).
      Repeated and one-way analyses of variance (ANOVAs), Pearson's chi-square tests,
      and correlation coefficients were used for statistical comparisons. Subjects
      slept an average of 06:28 h/night. Actigraphic sleep parameters, such as sleep
      duration, sleep efficiency, wake after sleep onset, and sleep latency, did not
      differ between chronotypes. Results also show that evening types (n = 17)
      presented lower subjective sleep quality than intermediate types (n = 58) and
      morning types (n = 13). Moreover, evening types reported higher levels of chronic
      work-related fatigue, exhibited less regular social rhythms, and were exposed to
      lower levels of light during their waking hours (between 2 and 11 h after wake
      time) as compared to intermediate types and morning types. In addition, exposure
      to light intensities between 100 and 500 lux was lower in evening types than in
      intermediate types and morning types. However, bright light exposure (>= 1000
      lux) did not differ between chronotypes. In conclusion, results suggest that
      student workers may constitute a high-risk population for sleep deprivation.
      Evening types seemed to cope less well with sleep deprivation, reporting poorer
      sleep quality and higher levels of work-related fatigue than intermediate types
      and morning types. The higher chronic work-related fatigue of evening types may
      be linked to their attenuated level of light exposure and weaker social
      zeitgebers. These results add credence to the hypothesis that eveningness entails
      a higher risk of health-impairing behaviors.

PMID- 22390243
TI  - Impact of perinatal photoperiod on the chronotype of 11- to 18-year-olds in
      northern European Russia.
AB  - The study investigates the effect of the month of birth and ambient light
      conditions at birth on sleep length and chronotype among residents of high
      latitudes. The authors surveyed 1172 persons (609 girls, 563 boys) age 11 to 18
      yrs living in five villages and four towns located between 59.5 degrees N and
      67.6 degrees N latitude. Survey participation was voluntary and anonymous. Sleep
      length and chronotype were assessed using the Munich chronotype questionnaire
      (MCTQ). The study showed the sleep length and chronotype of the children and
      adolescents depended on sex, age, type of settlement (town/village), and latitude
      of residence. Latitude exerted a stronger impact on sleep length and chronotype
      of children and adolescents living in villages than on those of their urban
      counterparts. Month of birth had no effect on sleep length and chronotype. There
      was a significant effect of the time of sunrise, sunset, and day length at birth
      on the chronotype of children and adolescents. A later chronotype was observed in
      the sample of young persons living above the Arctic Circle who were born during
      the polar day and polar night.

PMID- 22390244
TI  - Relation of chronotype to sleep complaints in the general Finnish population.
AB  - Individuals show variation in their preference for the daily timing of
      activities. In this study the authors analyzed whether chronotypes associate with
      sleep duration and sleep-related complaints. The authors used the National
      FINRISK Study 2007 Survey data on 3696 women and 3162 men, representative of the
      Finnish population aged 25 yrs and older, for the assessment of chronotype and
      self-reported sleep. Evening types experienced insomnia symptoms, had nightmares,
      and had used recently hypnotics significantly more often than other chronotypes
      among both men and women. In a multinominal logistic regression model predicting
      insufficient sleep, the association of eveningness with insufficient sleep was
      not abolished after adjustment for sex, age, and sleep duration. The prevalence
      of short sleepers was significantly higher in evening types among men than among
      women, whereas that of long sleepers was significantly higher in evening types
      among both men and women, as compared with the other chronotypes. These results
      indicate that eveningness predisposes individuals to a range of sleep complaints.

PMID- 22390245
TI  - Class start times, sleep, and academic performance in college: a path analysis.
AB  - Path analysis was used to examine the relationship between class start times,
      sleep, circadian preference, and academic performance in college-aged adults.
      Consistent with observations in middle and high school students, college students
      with later class start times slept longer, experienced less daytime sleepiness,
      and were less likely to miss class. Chronotype was an important moderator of
      sleep schedules and daytime functioning; those with morning preference went to
      bed and woke up earlier and functioned better throughout the day. The benefits of
      taking later classes did not extend to academic performance, however; grades were
      somewhat lower in students with predominantly late class schedules. Furthermore,
      students taking later classes were at greater risk for increased alcohol
      consumption, and among all the factors affecting academic performance, alcohol
      misuse exerted the strongest effect. Thus, these results indicate that later
      class start times in college, while allowing for more sleep, also increase the
      likelihood of alcohol misuse, ultimately impeding academic success.

PMID- 22390246
TI  - Impact of nightshift work on overweight and abdominal obesity among workers of a
      poultry processing plant in southern Brazil.
AB  - The authors examined the associations of shiftwork with overweight and abdominal
      obesity through a cross-sectional study of 1206 employees 18 to 50 yrs of age who
      were working on a production line in a poultry processing plant. Night-shift
      workers (n = 800) were considered exposed, whereas day shiftworkers (n = 406)
      were considered nonexposed. Overweight was defined as a body mass index >= 25
      kg/m(2) and abdominal obesity as a waist circumference >= 88 cm in women and >=
      102 cm in men. The mean age of the workers was 30.5 yrs (standard deviation = 8.7
      yrs), and 65.2% were women. Nightshift workers compared to dayshift workers
      showed higher prevalences of overweight (42.2% vs. 34.3%; p= .020) and abdominal
      obesity (24.9% vs. 19.5%; p = .037). After adjusting for sociodemographics,
      parental overweight status, behavioral characteristics, and sleep
      characteristics, including hours of sleep, the prevalence ratios for overweight
      and abdominal obesity were 1.27 (95% confidence interval [ CI]: 1.00-1.61) and
      1.45 (95% CI: 1.10-1.92), respectively, for the nightshift workers compared to
      the dayshift workers. A consistent finding in our study was the independent
      contribution of night shiftwork to overweight and abdominal obesity among
      Brazilian workers. Further studies are needed to understand the biological
      mechanisms involved and the complex behavioral and social adaptations experienced
      by night-shift workers.

PMID- 22390247
TI  - Unaltered instrumental learning and attenuated body-weight gain in rats during
      non-rotating simulated shiftwork.
AB  - Exposure to shiftwork has been associated with multiple health disorders and
      cognitive impairments in humans. We tested if we could replicate metabolic and
      cognitive consequences of shiftwork, as reported in humans, in a rat model
      comparable to 5 wks of non-rotating night shifts. The following hypotheses were
      addressed: (i) shiftwork enhances body-weight gain, which would indicate
      metabolic effects; and (ii) shiftwork negatively affects learning of a simple
      goal-directed behavior, i.e., the association of lever pressing with food reward
      (instrumental learning), which would indicate cognitive effects. We used a novel
      method of forced locomotion to model work during the animals' normal resting
      period. We first show that Wistar rats, indeed, are active throughout a shiftwork
      protocol. In contrast with previous findings, the shiftwork protocol attenuated
      the normal weight gain to 76 +/- 8 g in 5 wks as compared to 123 +/- 15 g in the
      control group. The discrepancy with previous work may be explained by the
      concurrent observation that with our shiftwork protocol rats did not adjust their
      between-work circadian activity pattern. They maintained a normal level of
      activity during the "off-work" periods. In the control experiment, rats were kept
      active during the dark period, normally dominated by activity. This demonstrated
      that forced activity, per se, did not affect body-weight gain (mean +/- SEM: 85
      +/- 11 g over 5 wks as compared to 84 +/- 11 g in the control group). Rats were
      trained on an instrumental learning paradigm during the fifth week of the
      protocol. All groups showed equivalent increases in lever pressing from the first
      (3.8 +/- .7) to the sixth (21.3 +/- 2.4) session, and needed a similar amount of
      sessions (5.1 +/- .3) to reach a learning criterion (>= 27 out of 30 lever
      presses). These results suggest that while on prolonged non-rotating shiftwork,
      not fully reversing the circadian rhythm might actually be beneficial to prevent
      body-weight gain and cognitive impairments.

PMID- 22390248
TI  - Altered circadian rhythm of melatonin concentrations in hypocretin-deficient men.
AB  - Hypocretin deficiency causes narcolepsy. It is unknown whether melatonin
      secretion is affected in this sleep disorder. Therefore, in both narcolepsy
      patients and matched controls, the authors measured plasma melatonin levels
      hourly for 24 h before and after 5 days of sodium oxybate (SXB) administration.
      Although mean melatonin concentrations were similar between patients and
      controls, in narcoleptics the percentage of 24-h melatonin secreted during the
      daytime was significantly higher, and melatonin secretion exhibited a weaker
      coupling to sleep. SXB did not affect melatonin secretion. These findings suggest
      that hypocretin deficiency might disturb both the circadian control of melatonin
      release and its temporal association with sleep.

PMID- 22390249
TI  - Relationship between infant and mother circadian rest-activity rhythm pre- and
      postpartum, in comparison to an infant with free-running rhythm.
AB  - Some infants show a free-running rhythm in their rest-activity. We do not know
      why, nor do we know exactly what the entrainment factors are for the development
      of the normal 24-h rest-activity rhythm. Actigraphic recordings on 10 primiparae
      during late pregnancy and these mothers and their infants during the 2nd, 6th,
      and 12th wks after birth were made over 3-5 continuous days to investigate
      maternal and infant entrainment. One infant showed a free-running rest-activity
      circadian rhythm. In late pregnancy, the period in the autocorrelogram of the
      mother with the free-running infant was longer than the significant period of the
      mean autocorrelogram of the mothers with non-free-running infants. The finding of
      this study indicates the free-running rhythm of infant is not reset by maternal
      entrainment factors.

PMID- 22390250
TI  - Do perinatal photoperiods imprint human chronobiology? Suggestion for a study
      into the possible signature of light in the Northern and Southern hemispheres.

PMID- 22390254
TI  - Induced abortion, pregnancy loss and intimate partner violence in Tanzania: a
      population based study.
AB  - BACKGROUND: Violence by an intimate partner is increasingly recognized as an
      important public and reproductive health issue. The aim of this study is to
      investigate the extent to which physical and/or sexual intimate partner violence
      is associated with induced abortion and pregnancy loss from other causes and to
      compare this with other, more commonly recognized explanatory factors. METHODS:
      This study analyzes the data of the Tanzania section of the WHO Multi-Country
      Study on Women's Health and Domestic Violence, a large population-based cross
      sectional survey of women of reproductive age in Dar es Salaam and Mbeya,
      Tanzania, conducted from 2001 to 2002. All women who answered positively to at
      least one of the questions about specific acts of physical or sexual violence
      committed by a partner towards her at any point in her life were considered to
      have experienced intimate partner violence. Associations between self reported
      induced abortion and pregnancy loss with intimate partner violence were analysed
      using multiple regression models. RESULTS: Lifetime physical and/or sexual
      intimate partner violence was reported by 41% and 56% of ever partnered, ever
      pregnant women in Dar es Salaam and Mbeya respectively. Among the ever pregnant,
      ever partnered women, 23% experienced involuntary pregnancy loss, while 7%
      reported induced abortion. Even after adjusting for other explanatory factors,
      women who experienced intimate partner violence were 1.6 (95%CI: 1.06,1.60) times
      more likely to report an pregnancy loss and 1.9 (95%CI: 1.30,2.89) times more
      likely to report an induced abortion. Intimate partner violence had a stronger
      influence on induced abortion and pregnancy loss than women's age, socio-economic
      status, and number of live born children. CONCLUSIONS: Intimate partner violence
      is likely to be an important influence on levels of induced abortion and
      pregnancy loss in Tanzania. Preventing intimate partner violence may therefore be
      beneficial for maternal health and pregnancy outcomes.

PMID- 22390256
TI  - Effects of nutrition and density in Culex pipiens.
AB  - Mosquito larvae face numerous biotic and abiotic challenges that affect their
      development and survivorship, as well as adult fitness. We conducted two
      experiments under semi-natural conditions to evaluate the effects of
      intraspecific competition, nutrient limitation and sub-lethal doses of malathion
      on individual life history traits in adult Culex pipiens (Diptera: Culicidae). In
      the first experiment, larvae of Cx. pipiens were reared at different
      intraspecific densities and exposed to sub-lethal doses of malathion. In the
      second experiment, different intraspecific densities of Cx. pipiens larvae were
      reared under conditions of low or high larval nutrients, and subsequent adults
      were fed on either water or 10% sucrose solution. Malathion treatment had
      relatively minor effects compared with density, which had significant negative
      effects on development rate, survivorship to adulthood, body size (wing length)
      and longevity. As larval density increased, a sex ratio distortion in
      survivorship to adulthood emerged, in which a bias towards males was apparent.
      Nutrient-rich larval environments alleviated, in part, the effects of increasing
      density and extended the lifespan of mosquitoes fed on water and 10% sucrose.
      Density-dependent alterations in adult longevity attributable to the larval
      environment are complex and show contrasting results depending on interactions
      with other environmental factors. This study suggests that larval resource
      availability and competition influence Cx. pipiens population growth correlates
      and have lasting effects on traits that relate to a mosquito's ability to vector
      pathogens.

PMID- 22390255
TI  - Oral health care and aspiration pneumonia in frail older people: a systematic
      literature review.
AB  - OBJECTIVE: To systematically review the literature on oral health care
      interventions in frail older people and the effect on the incidence of aspiration
      pneumonia. BACKGROUND: Oral health care seems to play an important role in the
      prevention of aspiration pneumonia in frail older people. METHODS: Pubmed, Web of
      Science, Cochrane Library, EMBASE and CINAHL were searched for eligible
      intervention studies. Only publications with regard to hospitalized or
      institutionalized older people, who were not dependent on mechanical ventilation
      were eligible. Two authors independently assessed the publications for their
      methodological quality. RESULTS: Five publications were included and reviewed.
      Two studies showed that improvement of oral health care diminished the risk of
      developing aspiration pneumonia and the risk of dying from aspiration pneumonia
      directly. The three studies remaining showed that adequate oral health care
      decreased the amount of potential respiratory pathogens and suggested a reduction
      in the risk of aspiration pneumonia by improving the swallowing reflex and cough
      reflex sensitivity. CONCLUSIONS: According to the results of the current
      systematic literature review oral health care, consisting of tooth brushing after
      each meal, cleaning dentures once a day, and professional oral health care once a
      week, seems the best intervention to reduce the incidence of aspiration
      pneumonia.

PMID- 22390257
TI  - Quantification of BK viral load in asymptomatic renal allograft recipients.
AB  - INTRODUCTION: Polyoma BK virus (BKV) has recently been identified to cause renal
      allograft dysfunction, which manifests as polyomavirus-associated nephropathy
      (PVAN). However, the presence and level of BKV DNA in renal allograft patients
      with good and stable renal function have remained undetermined. METHODS: In this
      prospective study, serum samples were collected from a total of 45 renal
      allograft recipients with serum creatinine <155 MUmol/L. In 17 patients, whose
      duration of transplantation was under 2 years, samples were collected at 3-4
      month intervals for up to 2 years after transplantation. BK viral load was
      quantified using quantitative polymerase chain reaction (Q-PCR). RESULTS: The BK
      viral load in asymptomatic renal allograft recipients was independent of the
      duration of transplantation and did not correlate with allograft function. The
      mean (+/- SD) level of viremia was 552.80 +/- 1931.00 genome copies/mL, with
      92.9% of patients having low levels of viremia corresponding to <1 * 10(3)
      copies/mL. In contrast, patients with proven PVAN had levels in the range of
      10(6) copies/mL. CONCLUSIONS: The prevailing BK viral load in asymptomatic renal
      allograft patients is quantifiably low. Our findings may guide optimal
      immunosuppressive modulation in PVAN cases, where judicious manipulation of
      immunosuppression is required without inciting allograft rejection.

PMID- 22390258
TI  - Tumours of the retrorectal space: management and outcome of a heterogeneous group
      of diseases.
AB  - AIM: Retrorectal tumours are a rare and complex entity in adults and children.
      They present a varied symptomatology and their treatment is very different
      according to their histology. We aimed to evaluate our experience of tumours of
      the retrorectal space. METHOD: Forty patients with retrorectal tumours were
      divided into two groups according to age. The variables analysed were sex, signs
      and symptoms, complementary examinations, surgical approaches, adjuvant
      therapies, pathological analyses, recurrence and survival. RESULTS: Symptoms
      across the 30 adults varied--back pain (18) was the most common. Surgical
      intervention was performed on 20 patients; the rest were candidates for other
      treatments: five metastatic disease, two lymphomas and two Ewing tumour. The most
      common surgical approach was posterior, with 10 cases (50%). In all, 70% of adult
      tumours were malignant, with chordoma (30%) and metastases (20%) being the most
      common lesions. The most frequent benign lesion was hamartoma (10%). The 1- and 5
      year mortality rates were 23.8% and 38.1%, respectively. In the paediatric group,
      three patients were diagnosed in utero. The symptoms among children varied and
      all were operated upon. The most frequent tumour was teratoma. Overall mortality
      was 20%. CONCLUSIONS: Given their complexity, these tumours should be addressed
      by experts and all treatment options must be contemplated. They continue to
      present a challenge, above all in malignant tumours where the tumour cannot be
      controlled at a locoregional level.

PMID- 22390259
TI  - Nowadays which emergency contraception? Comparison between past and present:
      latest news in terms of clinical efficacy, side effects and contraindications.
AB  - Despite many highly effective methods of contraception are available nowadays,
      many pregnancies are unintended. Emergency contraception (EC) is the use of drug
      or device after unprotected intercourse to prevent an unwanted pregnancy. It is a
      woman's last chance to prevent unintended pregnancy. Nevertheless the confusion
      about mechanisms of action, side effects, clinical efficacy and controindications
      makes the intervention underused in every setting investigated. So far
      levonorgestrel (LNG) has been considered the gold standard for oral EC. Today, a
      new type of second generation progesterone receptor modulator, ulipristal acetate
      (UPA) has been proposed as a more effective drug than LNG in prevention of
      unwanted pregnancies by delaying or inhibiting ovulation; even if many other
      devices are disposable in commerce. We revised the literature to concern most of
      the data available on the role of EC and moreover clarifying the available
      methods, the action windows of the accessible devices, the adverse events and the
      controindications.

PMID- 22390260
TI  - A cross-sectional assessment of health-related quality of life (HRQoL) among
      hypertensive patients in Pakistan.
AB  - OBJECTIVE: To describe the health-related quality of life (HRQoL) profile of
      hypertensive population in Pakistan. METHODS: A cross-sectional descriptive study
      was undertaken with a cohort of 385 hypertensive patients attending two public
      hospitals in Quetta city, Pakistan. The EuroQoL EQ-5D scale was used for the
      assessment of HRQoL. EQ-5D is a standardized instrument for use as a measure of
      health outcome and is used in the clinical and economic evaluation of health care
      as well as population health surveys. The HRQoL was scored using values derived
      from the UK general population survey. P <= 0.05 was taken as significant.
      RESULTS: Two hundred and sixty-five (68.85%) respondents were men with 3.01 +/-
      0.939 years of history of hypertension. Majority (n = 186, 48.3%) were
      categorized in age group of 28-37 years with mean age of 39.02 +/- 6.596.
      Education, income and locality had significant relation with HRQoL score. HRQoL
      was measured poor in our study patients (0.4674 +/- 0.2844). CONCLUSION:
      Hypertension has an adverse effect on patients' well-being and HRQoL. Results
      from this study could be useful in clinical practice, particularly in early
      treatment of hypertension, at point where improving HRQoL is still possible.

PMID- 22390262
TI  - Enantiopure C1-symmetric bis(imino)pyridine cobalt complexes for asymmetric
      alkene hydrogenation.
AB  - Enantiopure C(1)-symmetric bis(imino)pyridine cobalt chloride, methyl, hydride,
      and cyclometalated complexes have been synthesized and characterized. These
      complexes are active as catalysts for the enantioselective hydrogenation of
      geminal-disubstituted olefins.

PMID- 22390261
TI  - Blood-brain barrier permeation and efflux exclusion of anticholinergics used in
      the treatment of overactive bladder.
AB  - Overactive bladder (OAB) is a common condition, particularly in the elderly.
      Anticholinergic agents are the mainstay of pharmacological treatment of OAB;
      however, many anticholinergics can cross the blood-brain barrier (BBB) and may
      cause central nervous system (CNS) effects, including cognitive deficits, which
      can be especially detrimental in older patients. Many anticholinergics have the
      potential to cause adverse CNS effects due to muscarinic (M(1)) receptor binding
      in the brain. Of note, permeability of the BBB increases with age and can also be
      affected by trauma, stress, and some diseases and medications. Passive crossing
      of a molecule across the BBB into the brain is dependent upon its physicochemical
      properties. Molecular characteristics that hinder passive BBB penetration include
      a large molecular size, positive or negative ionic charge at physiological pH,
      and a hydrophilic structure. Active transport across the BBB is dependent upon
      protein-mediated transporter systems, such as that of permeability-glycoprotein
      (P-gp), which occurs only for P-gp substrates, such as trospium chloride,
      darifenacin and fesoterodine. Reliance on active transport can be problematic
      since genetic polymorphisms of P-gp exist, and many commonly used drugs and even
      some foods are P-gp inhibitors or are substrates themselves and, due to
      competition, can reduce the amount of the drug that is actively transported out
      of the CNS. Therefore, for drugs that are preferred not to cross into the CNS,
      such as potent anticholinergics intended for the bladder, it is optimal to have
      minimal passive crossing of the BBB, although it may also be beneficial for the
      drug to be a substrate for an active efflux transport system. Anticholinergics
      demonstrate different propensities to cross the BBB. Darifenacin, fesoterodine
      and trospium chloride are substrates for P-gp and, therefore, are actively
      transported away from the brain. In addition, trospium chloride has not been
      detected in cerebrospinal fluid assays and does not appear to have significant
      CNS penetration. This article reviews the properties of anticholinergics that
      affect BBB penetration and active transport out of the CNS, discusses issues of
      increased BBB permeability in patients with OAB, and examines the clinical
      implications of BBB penetration on adverse events associated with
      anticholinergics.

PMID- 22390263
TI  - Synthesis of dopamine and serotonin derivatives for immobilization on a solid
      support.
AB  - The two important neurotransmitters dopamine and serotonin are synthesized with
      short PEG tethers and immobilized on a magnetic solid support. The tether is
      attached to the aromatic moiety of the neurotransmitters to conserve their
      original functional groups. This approach causes minimal alteration of the
      original structure with the aim of optimizing the immobilized neurotransmitters
      for aptamer selection by SELEX. For the dopamine derivative, the tether is
      attached to the aromatic core of a dopamine precursor by the Sonogashira
      reaction. For serotonin, a link to the indole core is introduced by a Claisen
      rearrangement from the allylated phenol moiety of serotonin. The tethers are
      azide-functionalized, which enables coupling to alkyne-modified magnetic beads.
      The coupling to the magnetic beads is quantified by UV spectroscopy using Fmoc
      monitoring of the immobilized dopamine and serotonin derivatives.

PMID- 22390264
TI  - ERN and the placebo: a misattribution approach to studying the arousal properties
      of the error-related negativity.
AB  - Performance monitoring in the anterior cingulate cortex (ACC) has largely been
      viewed as a cognitive, computational process devoid of emotion. A growing body of
      research, however, suggests that performance is moderated by motivational
      engagement and that a signal generated by the ACC, the error-related negativity
      (ERN), may partially reflect a distress response to errors. Although suggestive,
      this past work is hampered by use of correlational designs or by designs that
      confound affect and cognitive performance. Here we use the misattribution of
      arousal paradigm--an experimental paradigm that pilot research shows can
      dissociate affect from cognitive performance--to investigate the extent to which
      the ERN has arousal properties. Forty university students completed a
      misattribution of arousal paradigm by consuming a beverage they believed would
      either increase their anxiety or would have no side effects and then completed a
      go/no-go task while we recorded ERNs. Results indicate that participants who were
      given the opportunity to misattribute arousal exhibited a reduced ERN compared
      with participants who were not given any misattribution cues. This occurred
      despite no measurable differences in performance on the go/no-go task. In
      addition, correlations between the ERN and behavior were observed only for
      participants who did not misattribute their arousal to the placebo beverage.
      Taken together, these results suggest that the ERN is dissociable from cognitive
      performance but not negative affect.

PMID- 22390265
TI  - A tri-reference point theory of decision making under risk.
AB  - The tri-reference point (TRP) theory takes into account minimum requirements
      (MR), the status quo (SQ), and goals (G) in decision making under risk. The 3
      reference points demarcate risky outcomes and risk perception into 4 functional
      regions: success (expected value of x >= G), gain (SQ < * < G), loss (MR <= x <
      SQ), and failure (x < MR). The psychological impact of achieving or failing to
      achieve these reference points is rank ordered as MR > G > SQ. We present TRP
      assumptions and value functions and a mathematical formalization of the theory.
      We conducted empirical tests of crucial TRP predictions using both explicit and
      implicit reference points. We show that decision makers consider both G and MR
      and give greater weight to MR than G, indicating failure aversion (i.e., the
      disutility of a failure is greater than the utility of a success in the same
      task) in addition to loss aversion (i.e., the disutility of a loss is greater
      than the utility of the same amount of gain). Captured by a double-S shaped value
      function with 3 inflection points, risk preferences switched between risk seeking
      and risk aversion when the distribution of a gamble straddled a different
      reference point. The existence of MR (not G) significantly shifted choice
      preference toward risk aversion even when the outcome distribution of a gamble
      was well above the MR. Single reference point based models such as prospect
      theory cannot consistently account for these findings. The TRP theory provides
      simple guidelines for evaluating risky choices for individuals and organizational
      management.

PMID- 22390266
TI  - Improving working memory efficiency by reframing metacognitive interpretation of
      task difficulty.
AB  - Working memory capacity, our ability to manage incoming information for
      processing purposes, predicts achievement on a wide range of intellectual
      abilities. Three randomized experiments (N = 310) tested the effectiveness of a
      brief psychological intervention designed to boost working memory efficiency
      (i.e., state working memory capacity) by alleviating concerns about incompetence
      subtly generated by demanding tasks. Sixth graders either received or did not
      receive a prior 10-min intervention designed to reframe metacognitive
      interpretation of difficulty as indicative of learning rather than of self
      limitation. The intervention improved children's working memory span and reading
      comprehension and also reduced the accessibility of self-related thoughts of
      incompetence. These findings demonstrate that constructing a psychologically safe
      environment through reframing metacognitive interpretation of subjective
      difficulty can allow children to express their full cognitive potential.

PMID- 22390267
TI  - The physical burdens of secrecy.
AB  - The present work examined whether secrets are experienced as physical burdens,
      thereby influencing perception and action. Four studies examined the behavior of
      people who harbored important secrets, such as secrets concerning infidelity and
      sexual orientation. People who recalled, were preoccupied with, or suppressed an
      important secret estimated hills to be steeper, perceived distances to be
      farther, indicated that physical tasks would require more effort, and were less
      likely to help others with physical tasks. The more burdensome the secret and the
      more thought devoted to it, the more perception and action were influenced in a
      manner similar to carrying physical weight. Thus, as with physical burdens,
      secrets weigh people down.

PMID- 22390268
TI  - Effects of surface chemistry on the generation of reactive oxygen species by
      copper nanoparticles.
AB  - Mercaptocarboxylic acids with different carbon chain lengths were used for
      stabilizing uniform 15 nm copper nanoparticles. The effects of surface chemistry
      such as ligand type and surface oxidation on the reactive oxygen species (ROS)
      generated by the copper nanoparticles were examined. Transmission electron
      microscopy (TEM), powder X-ray diffraction (PXRD), UV-vis spectroscopy, and an
      acellular ROS assay show that ROS generation is closely related to the surface
      oxidation of copper nanoparticles. It was found that the copper nanoparticles
      with longer chain ligands had surfaces that were better protected from oxidation
      and a corresponding lower ROS generating capacity than did particles with shorter
      chain ligands. Conversely, the copper nanoparticles with greater surface
      oxidation also had higher ROS generating capacity.

PMID- 22390269
TI  - Placebo response changes depending on the neuropathic pain syndrome: results of a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To compare placebo responses in neuropathic pain syndromes. DESIGN:
      Systematic literature review and meta-analysis. SETTING AND PATIENTS: Randomized
      placebo-controlled trials assessing pain intensity or pain relief in any
      neuropathic pain syndrome published since 1995 with >=5days follow-up.
      INTERVENTIONS: Placebo response. OUTCOME MEASURES: Pain intensity and responder
      rates (proportion reporting >=50% pain relief). Meta-regression models were
      built. RESULTS: Ninety-four studies (N=5,317) were included in the pain intensity
      analysis; 47 studies (N=3,087) were included in the responder analysis. After
      controlling for potential confounders (e.g., subject characteristics, study
      design characteristics), the placebo response was found to be large and varied
      with the pain syndrome. Compared with diabetic neuropathic/polyneuropathic pain
      (DPN), the placebo response for a decline in pain intensity and responder rate
      was smaller in trials that assessed central pain and postherpetic neuralgia (PHN)
      and larger in trials that assessed HIV pain. The model-predicted mean decrease
      (95% confidence interval [CI]) from baseline in pain intensity (0-10 scale) was
      as follows: DPN, 1.45 (1.35 to 1.55); PHN, 1.16 (1.03 to 1.29); central pain,
      0.44 (-0.41 to 1.30); HIV pain, 1.82 (1.51 to 2.12). The predicted responder
      rates (95% CI) were as follows: DPN, 20% (14.6 to 25.8); PHN, 11.5% (8.4 to
      14.5); central pain, 7.2% (2.1 to 12.3); HIV pain, 42.8% (34.9 to 50.7). The type
      of treatment in the active arm also influenced the placebo response. CONCLUSIONS:
      Placebo response is influenced by the pain syndrome evaluated. These differences
      should be considered when evaluating novel compounds for the treatment of
      neuropathic pain conditions.

PMID- 22390270
TI  - Orthopantomographic evaluation of canine and first premolar using Demirjian's
      stages in central India: new approach to forensic age estimation.
AB  - Teeth development is widely used for age estimation in forensic science. The aims
      of this study were as follows: first, to establish Indian data on canine and
      first premolar development for age estimation and second, to investigate
      population differences in teeth development. Orthopantomograms of 340 Indian
      children aged between 5 and 14 years were analyzed. Demirjian's stages were
      recorded for the developmental evaluation of canine and first premolar and for
      further descriptive statistical analysis. A two-way ANOVA was performed to test
      the significance of difference in teeth development by sex and stage. A one-way
      ANOVA was performed to investigate population differences in teeth development.
      Results showed statistically significant differences in teeth development by sex
      and stage. Accordingly, teeth development was earlier in girls. No statistically
      significant differences were observed in timings of Demirjian's stages among
      different populations. In conclusion, the findings of this study could be used
      for age estimation of Indian children.

PMID- 22390271
TI  - Mixing properties of sphingomyelin ceramide bilayers: a simulation study.
AB  - Ceramide is the simplest molecule in the class of glycosphingolipids composed of
      a sphingosine backbone and acyl moiety. It plays significant roles in cell
      signaling; apoptosis; binding of hormones, toxins, and viruses; and many other
      biologically important functions. Sphingomyelin, ceramide with a
      phosphotidylcholine headgroup, is another biologically vital lipid present in the
      myelin sheath of nerve cell axons. Regions with high concentrations of ceramide
      can be formed in biological membranes composed of sphingomyelin by enzymatic
      catalysis with sphingomyelinase. To better understand the biophysical and
      thermodynamic properties of these molecules and their mixtures, we have preformed
      NPT molecular dynamics simulations of hydrated 16:0 sphingomyelin bilayers with
      increasing concentrations of 16:0 ceramide at 323, 332, 340, and 358 K. From
      analyses of electron densities, hydrogen bonding, NMR order parameters, partial
      molecular volume, and partial molecular area, we have identified possible
      structural changes corresponding to liquid ordered and liquid disordered phases.
      These structural changes are the results of changes in intra- and intermolecular
      hydrogen bonds between SM and Cer molecules. Our results correspond to DSC
      experiments for sphingomyelin bilayer concentrations up to 50% Cer. Above 50%
      concentration, we observe conformational changes in the SM headgroup similar to
      that of the umbrella model for lipid cholesterol mixtures.

PMID- 22390272
TI  - A NOVel ELISPOT assay to quantify HLA-specific B cells in HLA-immunized
      individuals.
AB  - Quantification of the humoral alloimmune response is generally achieved by
      measuring serum HLA antibodies, which provides no information about the cells
      involved in the humoral immune response. Therefore, we have developed an HLA
      specific B-cell ELISPOT assay allowing for quantification of B cells producing
      HLA antibodies. We used recombinant HLA monomers as target in the ELISPOT assay.
      Validation was performed with human B-cell hybridomas producing HLA antibodies.
      Subsequently, we quantified B cells producing HLA antibodies in HLA-immunized
      individuals, non-HLA-immunized individuals and transplant patients with serum HLA
      antibodies. B-cell hybridomas exclusively formed spots against HLA molecules of
      corresponding specificity with the sensitivity similar to that found in total IgG
      ELISPOT assays. HLA-immunized healthy individuals showed up to 182 HLA-specific B
      cells per million total B cells while nonimmunized individuals had none. Patients
      who were immunized by an HLA-A2-mismatched graft had up to 143 HLA-A2-specific B
      cells per million total B cells. In conclusion, we have developed and validated a
      highly specific and sensitive HLA-specific B-cell ELISPOT assay, which needs
      further validation in a larger series of transplant patients. This technique
      constitutes a new tool for quantifying humoral immune responses.

PMID- 22390273
TI  - Information processing in adolescents with bipolar I disorder.
AB  - BACKGROUND: Cognitive models of bipolar I disorder (BD) may aid in identification
      of children who are especially vulnerable to chronic mood dysregulation.
      Information-processing biases related to memory and attention likely play a role
      in the development and persistence of BD among adolescents; however, these biases
      have not been extensively studied in youth with BD. METHODS: We administered the
      self-referent encoding task and the dot-probe task to adolescents with bipolar I
      disorder (BD, n = 35) and a demographically similar healthy comparison group (HC,
      n = 25) at baseline, and at a 1-year follow-up in a subset of this cohort (n = 22
      per group). RESULTS: At both baseline and 1-year follow-up, there were
      significant interactions of group (BD, HC) and valence of stimulus (positive,
      negative adjective) on endorsement and recall of self-referent adjectives. HC
      adolescents endorsed and recalled more positive self-referent adjectives at
      baseline and follow-up while adolescents with BD endorsed and recalled more
      negative self-referent adjectives at baseline but not follow-up. Over time,
      depression symptomatology was associated with impaired memory for positive self
      referent adjectives. There were no group differences in attentional bias at
      either time points. CONCLUSIONS: Adolescents with BD exhibit bias away from
      endorsement and recall of positive adjectives, which remained stable over time
      and independent of mood state.

PMID- 22390274
TI  - Advanced biorefinery in lower termite-effect of combined pretreatment during the
      chewing process.
AB  - BACKGROUND: Currently the major barrier in biomass utilization is the lack of an
      effective pretreatment of plant cell wall so that the carbohydrates can
      subsequently be hydrolyzed into sugars for fermentation into fuel or chemical
      molecules. Termites are highly effective in degrading lignocellulosics and thus
      can be used as model biological systems for studying plant cell wall degradation.
      RESULTS: We discovered a combination of specific structural and compositional
      modification of the lignin framework and partial degradation of carbohydrates
      that occurs in softwood with physical chewing by the termite, Coptotermes
      formosanus, which are critical for efficient cell wall digestion. Comparative
      studies on the termite-chewed and native (control) softwood tissues at the same
      size were conducted with the aid of advanced analytical techniques such as
      pyrolysis gas chromatography mass spectrometry, attenuated total reflectance
      Fourier transform infrared spectroscopy and thermogravimetry. The results
      strongly suggest a significant increase in the softwood cellulose enzymatic
      digestibility after termite chewing, accompanied with utilization of
      holocellulosic counterparts and an increase in the hydrolysable capacity of
      lignin collectively. In other words, the termite mechanical chewing process
      combines with specific biological pretreatment on the lignin counterpart in the
      plant cell wall, resulting in increased enzymatic cellulose digestibility in
      vitro. The specific lignin unlocking mechanism at this chewing stage comprises
      mainly of the cleavage of specific bonds from the lignin network and the
      modification and redistribution of functional groups in the resulting chewed
      plant tissue, which better expose the carbohydrate within the plant cell wall.
      Moreover, cleavage of the bond between the holocellulosic network and lignin
      molecule during the chewing process results in much better exposure of the
      biomass carbohydrate. CONCLUSION: Collectively, these data indicate the
      participation of lignin-related enzyme(s) or polypeptide(s) and/or esterase(s),
      along with involvement of cellulases and hemicellulases in the chewing process of
      C. formosanus, resulting in an efficient pretreatment of biomass through a
      combination of mechanical and enzymatic processes. This pretreatment could be
      mimicked for industrial biomass conversion.

PMID- 22390275
TI  - Incidence and prevalence of Parkinson's disease in Buenos Aires City, Argentina.
AB  - BACKGROUND AND PURPOSE: Epidemiologic studies of incidence and prevalence in
      Parkinson's Disease (PD) show highly variable results. Despite the large number
      of studies performed worldwide during the last decades, little is known about its
      prevalence in South America and no incidence studies have been performed. The
      goal of this study is to assess the incidence and prevalence of PD in a health
      maintenance organization from Buenos Aires City, the capital city of Argentina.
      METHODS: The population were all members of the 'Plan de Salud, Hospital Italiano
      de Buenos Aires', a large prepaid health medical organization in Buenos Aires.
      From 1 January 2003 to 31 December 2008 patients diagnosed with PD according to
      Brain Bank of London diagnostic criteria were identified retrospectively.
      Incidence density was calculated with 95% confidence interval. RESULTS: Hundred
      and forty thousand people were followed for a total of 754,082 person-years. A
      total of 239 incident cases of PD were identified. Crude incidence density was
      31.2/100,000 person-years. Prevalence was 394/100,000 in the population older
      than 40 years. Male to female ratio was 1.31. CONCLUSIONS: This is the first
      study in South America that estimates the incidence of PD. Our results are
      consistent with other studies from other regions using similar methodologies.

PMID- 22390276
TI  - Tamoxifen-induced eccrine squamous syringometaplasia.
AB  - A 74-year-old woman had carcinoma of her right breast for which surgery was
      performed. Four weeks following the start of tamoxifen therapy, she developed
      papules and plaques over her face, trunk and limbs. A skin biopsy showed
      perivascular and periadnexal mixed inflammatory cellular infiltrate with
      fibroplasia. Notably, the dermis also showed squamous epithelial islands, which
      in foci were noted to be closely associated with eccrine epithelium. This was
      confirmed with double peroxidase - alkaline phosphatase immunohistochemistry -
      the eccrine lumina highlighted with carcinoembryonic antigen (polyclonal) and the
      squamous metaplasia positive for cytokeratin 5/6. Eccrine squamous
      syringometaplasia was diagnosed. With close clinicopathological correlation, the
      cutaneous eruption was attributed to tamoxifen. Following discontinuation of the
      drug, the eruption resolved. Eccrine squamous syringometaplasia has been reported
      to occur in association with diverse conditions, including skin ulcers, burns and
      as a cutaneous adverse drug reaction, most commonly to chemotherapeutic drugs.
      This is believed to be the first report involving tamoxifen.

PMID- 22390277
TI  - Temporary cardiac pacemaker treatment in five Norwegian regional hospitals.
AB  - OBJECTIVES: Over the last few decades the number of temporary pacemaker
      placements has declined, while the number of operators has increased. The present
      study was undertaken in order to assess the quality of present day temporary
      pacing in Norwegian general hospitals. DESIGN: Prospective, multi-center study
      from five general hospitals in Norway with a catchment area of 998,000
      inhabitants. All temporary pacing procedures performed at these hospitals during
      a 1-year period should be registered. RESULTS: Fifty patients were treated with
      temporary pacing and six repeated procedures were performed due to pacing
      failure. The yearly procedure-rate was five per 100,000 inhabitants. Twenty-nine
      physicians were involved in these procedures, of whom five were experienced
      implanters, and 18 physicians participated in only one procedure each. Following
      temporary pacing a permanent pacemaker was implanted in 60% of patients. In
      hospital mortality was 18%, and the incidence of bacteremia was 6%. CONCLUSIONS:
      Temporary pacemaker treatment is currently performed with less than the required
      amount of skill, with a high number of complications. Cardiologists on call and
      the possibility of fast-track permanent implantation could improve the quality of
      care of patients with acute bradyarrhythmias.

PMID- 22390278
TI  - Clock drawing in spatial neglect: a comprehensive analysis of clock perimeter,
      placement, and accuracy.
AB  - Clock drawings produced by right-brain-damaged (RBD) individuals with spatial
      neglect often contain an abundance of empty space on the left while numbers and
      hands are placed on the right. However, the clock perimeter is rarely compromised
      in neglect patients' drawings. By analysing clock drawings produced by 71 RBD and
      40 healthy adults, this study investigated whether the geometric characteristics
      of the clock perimeter reveal novel insights to understanding spatial neglect.
      Neglect participants drew smaller clocks than either healthy or non-neglect RBD
      participants. While healthy participants' clock perimeter was close to circular,
      RBD participants drew radially extended ellipses. The mechanisms for these
      phenomena were investigated by examining the relation between clock-drawing
      characteristics and performance on six subtests of the Behavioral Inattention
      Test (BIT). The findings indicated that the clock shape was independent of any
      BIT subtest or the drawing placement on the test sheet and that the clock size
      was significantly predicted by one BIT subtest: the poorer the figure and shape
      copying, the smaller the clock perimeter. Further analyses revealed that in all
      participants, clocks decreased in size as they were placed farther from the
      centre of the paper. However, even when neglect participants placed their clocks
      towards the centre of the page, they were smaller than those produced by healthy
      or non-neglect RBD participants. These results suggest a neglect-specific
      reduction in the subjectively available workspace for graphic production from
      memory, consistent with the hypothesis that neglect patients are impaired in the
      ability to enlarge the attentional aperture.

PMID- 22390280
TI  - Development of stable isotope dilution assays for the simultaneous quantitation
      of biogenic amines and polyamines in foods by LC-MS/MS.
AB  - Microbial amino acid metabolism may lead to substantial amounts of biogenic
      amines in either spontaneously fermented or spoiled foods. For products
      manufactured with starter cultures, it has been suggested that certain strains
      may produce higher amounts of such amines than others; however, to support
      efforts of food manufacturers in mitigating amine formation, reliable methods for
      amine quantitation are needed. Using 10 isotopically labeled biogenic amines as
      the internal standards, stable isotope dilution assays were developed for the
      quantitation of 12 biogenic amines and of the 2 polyamines, spermine and
      spermidine, in one LC-MS/MS run. Application of the method to several foods
      revealed high concentrations of, for example, tyramine and putrescine in salami
      and fermented cabbage, whereas histamine was highest in Parmesan cheese and
      fermented cabbage. On the other hand, ethanolamine was highest in red wine and
      Parmesan cheese. The results suggest that different amino acid decarboxylases are
      active in the respective foods depending on the microorganisms present. The
      polyamine spermine was highest in salami and tuna.

PMID- 22390279
TI  - Polo-like kinase 1 (PLK1) inhibition suppresses cell growth and enhances
      radiation sensitivity in medulloblastoma cells.
AB  - BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children
      and remains a therapeutic challenge due to its significant therapy-related
      morbidity. Polo-like kinase 1 (PLK1) is highly expressed in many cancers and
      regulates critical steps in mitotic progression. Recent studies suggest that
      targeting PLK1 with small molecule inhibitors is a promising approach to tumor
      therapy. METHODS: We examined the expression of PLK1 mRNA in medulloblastoma
      tumor samples using microarray analysis. The impact of PLK1 on cell proliferation
      was evaluated by depleting expression with RNA interference (RNAi) or by
      inhibiting function with the small molecule inhibitor BI 2536. Colony formation
      studies were performed to examine the impact of BI 2536 on medulloblastoma cell
      radiosensitivity. In addition, the impact of depleting PLK1 mRNA on tumor
      initiating cells was evaluated using tumor sphere assays. RESULTS: Analysis of
      gene expression in two independent cohorts revealed that PLK1 mRNA is
      overexpressed in some, but not all, medulloblastoma patient samples when compared
      to normal cerebellum. Inhibition of PLK1 by RNAi significantly decreased
      medulloblastoma cell proliferation and clonogenic potential and increased cell
      apoptosis. Similarly, a low nanomolar concentration of BI 2536, a small molecule
      inhibitor of PLK1, potently inhibited cell growth, strongly suppressed the colony
      forming ability, and increased cellular apoptosis of medulloblastoma cells.
      Furthermore, BI 2536 pretreatment sensitized medulloblastoma cells to ionizing
      radiation. Inhibition of PLK1 impaired tumor sphere formation of medulloblastoma
      cells and decreased the expression of SRY (sex determining region Y)-box 2 (SOX2)
      mRNA in tumor spheres indicating a possible role in targeting tumor initiating
      cells. CONCLUSIONS: Our data suggest that targeting PLK1 with small molecule
      inhibitors, in combination with radiation therapy, is a novel strategy in the
      treatment of medulloblastoma that warrants further investigation.

PMID- 22390281
TI  - Cellular mechanisms and intracellular signaling pathways for the modulation of
      eNOS in pulmonary arteries by 15-HETE.
AB  - The 15-hydroxyeicosatetraenoic acid (15-HETE), a lipid metabolite and
      vasoconstrictor, plays an important role in hypoxic contraction of pulmonary
      arteries (PAs) through working on smooth muscle cells (SMCs). Previous studies
      have shown that vascular endothelium is also involved in PAs tone regulation.
      However, little is known as to how the pulmonary artery endothelial cells (PAECs)
      are related to the 15-HETE-induced vasoconstriction and that which intracellular
      signaling systems are critical. To test this hypothesis, we examined PAs
      constriction in isolated rat PAs rings, the expression and activity of
      endothelial nitric oxide synthase (eNOS) with western blot, and nitric oxide (NO)
      production using the DAF-FM DA fluorescent indicator. The results showed that the
      15-HETE-induced PAs constriction was diminished in endothelium-intact rings. In
      the presence of the eNOS inhibitor L-NAME, vasoconstrictor responses to KCl were
      greater than the control. The activation of eNOS was activated by Ca2+ released
      from intracellular stores and the PI3K/Akt pathway. Phosphorylations of the eNOS
      at Ser-1177 and Akt at Ser-473 were necessary for their activity. A prolonged 15
      HETE treatment (30 min) led to a decrease in NO production by phosphorylation of
      eNOS at Thr-495, leading to augmentation of PAs constriction. Therefore, 15-HETE
      initially inhibited the PAs constriction through the endothelial NO system, and
      both Ca2+ and the PI3K/Akt signaling systems are required for the effects of 15
      HETE on PAs tone regulation.

PMID- 22390282
TI  - Mitochondrial gene therapy improves respiration, biogenesis, and transcription in
      G11778A Leber's hereditary optic neuropathy and T8993G Leigh's syndrome cells.
AB  - Many incurable mitochondrial disorders result from mutant mitochondrial DNA
      (mtDNA) and impaired respiration. Leigh's syndrome (LS) is a fatal
      neurodegenerative disorder of infants, and Leber's hereditary optic neuropathy
      (LHON) causes blindness in young adults. Treatment of LHON and LS cells harboring
      G11778A and T8993G mutant mtDNA, respectively, by >90%, with healthy donor mtDNA
      complexed with recombinant human mitochondrial transcription factor A (rhTFAM),
      improved mitochondrial respiration by ~1.2-fold in LHON cells and restored >50%
      ATP synthase function in LS cells. Mitochondrial replication, transcription, and
      translation of key respiratory genes and proteins were increased in the short
      term. Increased NRF1, TFAMB1, and TFAMA expression alluded to the activation of
      mitochondrial biogenesis as a mechanism for improving mitochondrial respiration.
      These results represent the development of a therapeutic approach for LHON and LS
      patients in the near future.

PMID- 22390283
TI  - Regioselective oxyalkylation of vinylarenes catalyzed by diatomite-supported
      manganese oxide nanoparticles.
AB  - A regioselective oxyalkylation reaction of vinylarenes with cyclic ethers was
      developed under the catalysis of a new heterogeneous catalyst, the diatomite
      supported Mn(3)O(4) nanoparticles (SMONP-1). The use of this heterogeneous
      catalyst provided a novel approach for the synthesis of alpha-carbonyled beta
      alkylated aryl derivatives via a sp(3) C-H bond functionalization under mild
      aerobic conditions.

PMID- 22390284
TI  - Serrated polyp detection rate during screening colonoscopy.
AB  - AIM: The adenoma detection rate is an important quality indicator for
      colonoscopy, but recently, serrated polyps of the large bowel have been
      recognized as important premalignant lesions. As they are often more difficult to
      see than adenomas, the detection rate of serrated polyps is set to become a more
      stringent indicator of quality in colonoscopy than adenoma detection rate. Here
      we aim to provide preliminary data on serrated polyp detection. METHOD: This is a
      retrospective review of prospectively collected data. Colonoscopies were
      stratified by one of six colorectal surgeons, each of whom had performed more
      than 1000 colonoscopies. Exams were separated by indication and the number of
      patients with at least one adenoma or one serrated polyp recorded. Time of
      withdrawal in normal examinations was noted. RESULTS: Eighteen thousand and three
      colonoscopies were included. Average completion rate was 96.3 +/- 1.2%. Mean
      serrated detection rate for all examinations was 20.6 +/- 4.8% and for screening
      examinations only was 13.9 +/- 5.0%. Corresponding means for adenoma detection
      were 31.5 +/- 6.7% and 20.7 +/- 4.1%, respectively. Simple regression of overall
      adenoma detection rate versus overall serrated detection rate was not significant
      (R = 0.571, P = 0.237), but was significant for screening exams (R = 0.854, P =
      0.031). There was a strong relationship between time of withdrawal and serrated
      detection rate (screening, R = 0.908, P = 0.012; overall, R = 0.956, P = 0.003).
      CONCLUSION: Taking time to withdraw the colonoscope is essential for maximum
      detection of serrated polyps. The ability to find adenomas does not necessarily
      correlate with an ability to find serrated polyps.

PMID- 22390285
TI  - Costs and benefits of electronic fetal monitoring.

PMID- 22390286
TI  - Design, synthesis, and characterization of mesogenic amine-capped nematic gold
      nanoparticles with surface-enhanced plasmonic resonances.
AB  - The use of the liquid-crystalline state to control the assembly of large (>5 nm)
      gold nanoparticles (NPs) is of considerable interest because of the promise of
      novel metamaterial properties of such systems. Here we report on a new approach
      for the preparation of large nematic gold NPs using a bifunctional capping agent
      that enables control over the particle size and serves as a linkage for
      subsequent functionalization with mesogenic groups. Properties of the NPs were
      characterized by HRTEM, NMR, DSC, TGA, UV/vis, OPM, and XRD studies. The results
      confirmed the formation of a stable nematic mesophase above 37.5  degrees C for
      NPs in the 6-11 nm size range.

PMID- 22390287
TI  - The Swiss Health Literacy Survey: development and psychometric properties of a
      multidimensional instrument to assess competencies for health.
AB  - BACKGROUND: Growing recognition of the role of citizens and patients in health
      and health care has placed a spotlight on health literacy and patient education.
      OBJECTIVE: To identify specific competencies for health in definitions of health
      literacy and patient-centred concepts and empirically test their dimensionality
      in the general population. METHODS: A thorough review of the literature on health
      literacy, self-management, patient empowerment, patient education and shared
      decision making revealed considerable conceptual overlap as competencies for
      health and identified a corpus of 30 generic competencies for health. A
      questionnaire containing 127 items covering the 30 competencies was fielded as a
      telephone interview in German, French and Italian among 1255 respondents randomly
      selected from the resident population in Switzerland. FINDINGS: Analyses with the
      software MPlus to model items with mixed response categories showed that the
      items do not load onto a single factor. Multifactorial models with good fit could
      be erected for each of five dimensions defined a priori and their corresponding
      competencies: information and knowledge (four competencies, 17 items), general
      cognitive skills (four competencies, 17 items), social roles (two competencies,
      seven items), medical management (four competencies, 27 items) and healthy
      lifestyle (two competencies, six items). Multiple indicators and multiple causes
      models identified problematic differential item functioning for only six items
      belonging to two competencies. CONCLUSIONS: The psychometric analyses of this
      instrument support broader conceptualization of health literacy not as a single
      competence but rather as a package of competencies for health.

PMID- 22390289
TI  - Semantic and affective salience: the role of meaning and preference in
      attentional capture and disengagement.
AB  - Emotion appears to have a substantial impact on a wide variety of attentional
      functions. However, stimuli that elicit affective responses also tend to be
      meaningful. Here we attempted to disentangle the effects of meaning from the
      effects of affect on attentional capture by irrelevant distractors. Experiment 1
      used a previously unfamiliar distractor stimulus, and manipulated the amount of
      knowledge provided to observers about the distractor. The results suggested that
      increases in meaning can reduce attentional capture. Experiments 2 and 3 used
      both familiar and unfamiliar symbols (baseball logos and flags, respectively) as
      distractors. Critically, of the two familiar symbols, one was rated as affective
      positive and the other was rated as affective-negative. As in Experiment 1, the
      results showed that unfamiliar distractors can capture attention. In addition,
      the results also suggested that the two affective distractors captured attention
      (so long as they were sufficiently intense). This finding suggests that while
      increased knowledge can reduce capture, affect can restore an item's ability to
      capture attention. Finally, the results of Experiment 4 showed that observers
      were slower to disengage from a negative item than from a positive item. This
      evidence emphasizes the differential roles of semantic knowledge versus affect on
      attentional capture.

PMID- 22390290
TI  - Going rogue in the spatial cuing paradigm: high spatial validity is insufficient
      to elicit voluntary shifts of attention.
AB  - Voluntary shifts of attention are often motivated in experimental contexts by
      using well-known symbols that accurately predict the direction of targets. The
      authors report 3 experiments, which showed that the presentation of predictive
      spatial information does not provide sufficient incentive to elicit voluntary
      shifts of attention. For instance, when allowed to spontaneously choose between
      using a 100%-valid spatial word cue versus searching without the aid of the cue,
      observers consistently searched for a unique target without the aid of the cue.
      Another experiment showed that observers' choice to use spatial word cues could
      be biased by providing dedicated time to process the cue before the target
      display appeared (i.e., nonzero, cue-target SOAs). Although this dedicated
      processing time has routinely been included in spatial cuing experiments, its
      incentive-inducing role has never been acknowledged. Implications for theories of
      both voluntary and involuntary control are discussed.

PMID- 22390288
TI  - Psychopathy increases perceived moral permissibility of accidents.
AB  - Psychopaths are notorious for their antisocial and immoral behavior, yet
      experimental studies have typically failed to identify deficits in their
      capacities for explicit moral judgment. We tested 20 criminal psychopaths and 25
      criminal nonpsychopaths on a moral judgment task featuring hypothetical scenarios
      that systematically varied an actor's intention and the action's outcome.
      Participants were instructed to evaluate four classes of actions: accidental
      harms, attempted harms, intentional harms, and neutral acts. Psychopaths showed a
      selective difference, compared with nonpsychopaths, in judging accidents, where
      one person harmed another unintentionally. Specifically, psychopaths judged these
      actions to be more morally permissible. We suggest that this pattern reflects
      psychopaths' failure to appreciate the emotional aspect of the victim's
      experience of harm. These findings provide direct evidence of abnormal moral
      judgment in psychopathy.

PMID- 22390291
TI  - Violation of the scalar property for time perception between 1 and 2 seconds:
      evidence from interval discrimination, reproduction, and categorization.
AB  - According to the hypothesis of a scalar property for time, the variability to
      time ratio should be constant. Three experiments tested the validity of this
      hypothesis in a restricted range of durations (standard values = 1, 1.3, 1.6, and
      1.9 s). In each experiment, time intervals to be discriminated, reproduced, or
      categorized were presented with 2, 4, or 6 brief successive auditory signals
      marking 1, 3, or 5 intervals, respectively. In Experiment 1, participants were
      asked to indicate whether the interval(s) within a second series of sounds were
      shorter or longer than those of the first. In Experiment 2, the standard interval
      had to be reproduced. In Experiment 3, after 10 presentations of the standard,
      participants had to categorize each comparison interval as shorter or longer than
      the standard. In addition to showing that performance was generally poorer when
      only 1 interval was presented and remained about the same regardless of whether 3
      or 5 intervals were presented (Experiments 1 and 3), the results demonstrated
      that the variability to time ratio is not constant across the standard interval
      conditions. Overall, the ratio is higher at 1.9 than at 1 s. This violation of
      scalar timing occurs whatever the method used and does not interact with the
      number-of-interval variable.

PMID- 22390293
TI  - Evidence for interaction between the stop signal and the Stroop task conflict.
AB  - Performance of the Stroop task reflects two conflicts--informational (between the
      incongruent word and ink color) and task (between relevant color naming and
      irrelevant word reading). The task conflict is usually not visible, and is only
      seen when task control is damaged. Using the stop-signal paradigm, a few studies
      demonstrated longer stop-signal reaction times for incongruent trials than for
      congruent trials. This indicates interaction between stopping and the
      informational conflict. Here we suggest that "zooming in" on task-control failure
      trials will reveal another interaction--between stopping and task conflict. To
      examine this suggestion, we combined stop-signal and Stroop tasks in the same
      experiment. When participants' control failed and erroneous responses to a stop
      signal occurred, a reverse facilitation emerged in the Stroop task (Experiment 1)
      and this was eliminated using methods that manipulated the emergence of the
      reverse facilitation (Experiment 2). Results from both experiments were
      replicated when all stimuli were used in the same task (Experiment 3). In
      erroneous response trials, only the task conflict increased, not the
      informational conflict. These results indicate that task conflict and stop-signal
      inhibition share a common control mechanism that is dissociable from the control
      mechanism activated by the informational conflict.

PMID- 22390292
TI  - Individual differences in the multisensory temporal binding window predict
      susceptibility to audiovisual illusions.
AB  - Human multisensory systems are known to bind inputs from the different sensory
      modalities into a unified percept, a process that leads to measurable behavioral
      benefits. This integrative process can be observed through multisensory
      illusions, including the McGurk effect and the sound-induced flash illusion, both
      of which demonstrate the ability of one sensory modality to modulate perception
      in a second modality. Such multisensory integration is highly dependent upon the
      temporal relationship of the different sensory inputs, with perceptual binding
      occurring within a limited range of asynchronies known as the temporal binding
      window (TBW). Previous studies have shown that this window is highly variable
      across individuals, but it is unclear how these variations in the TBW relate to
      an individual's ability to integrate multisensory cues. Here we provide evidence
      linking individual differences in multisensory temporal processes to differences
      in the individual's audiovisual integration of illusory stimuli. Our data provide
      strong evidence that the temporal processing of multiple sensory signals and the
      merging of multiple signals into a single, unified perception, are highly
      related. Specifically, the width of right side of an individuals' TBW, where the
      auditory stimulus follows the visual, is significantly correlated with the
      strength of illusory percepts, as indexed via both an increase in the strength of
      binding synchronous sensory signals and in an improvement in correctly
      dissociating asynchronous signals. These findings are discussed in terms of their
      possible neurobiological basis, relevance to the development of sensory
      integration, and possible importance for clinical conditions in which there is
      growing evidence that multisensory integration is compromised.

PMID- 22390294
TI  - Incidental and context-responsive activation of structure- and function-based
      action features during object identification.
AB  - Previous studies suggest that action representations are activated during object
      processing, even when task-irrelevant. In addition, there is evidence that
      lexical-semantic context may affect such activation during object processing.
      Finally, prior work from our laboratory and others indicates that function-based
      ("use") and structure-based ("move") action subtypes may differ in their
      activation characteristics. Most studies assessing such effects, however, have
      required manual object-relevant motor responses, thereby plausibly influencing
      the activation of action representations. The present work uses eyetracking and a
      Visual World Paradigm task without object-relevant actions to assess the time
      course of activation of action representations, as well as their responsiveness
      to lexical-semantic context. In two experiments, participants heard a target word
      and selected its referent from an array of four objects. Gaze fixations on
      nontarget objects signal activation of features shared between targets and
      nontargets. The experiments assessed activation of structure-based (Experiment 1)
      or function-based (Experiment 2) distractors, using neutral sentences ("S/he saw
      the....") or sentences with a relevant action verb (Experiment 1: "S/he picked up
      the...."; Experiment 2: "S/he used the...."). We observed task-irrelevant
      activations of action information in both experiments. In neutral contexts,
      structure-based activation was relatively faster-rising but more transient than
      function-based activation. Additionally, action verb contexts reliably modified
      patterns of activation in both Experiments. These data provide fine-grained
      information about the dynamics of activation of function-based and structure
      based actions in neutral and action-relevant contexts, in support of the "Two
      Action System" model of object and action processing (e.g., Buxbaum & Kalenine,
      2010).

PMID- 22390295
TI  - Spatiotemporal object history affects the selection of task-relevant properties.
AB  - For stable perception, we maintain mental representations of objects across space
      and time. What information is linked to such a representation? In this study, we
      extended our work showing that the spatiotemporal history of an object affects
      the way the object is attended the next time it is encountered. Observers
      conducted a visual search for a target among multiple distractors. Either the
      target location (Experiment 1) or the target feature (Experiment 2) could repeat
      from trial to trial. The entire visual search display was part of an object that
      could move in and out of view. Search was speeded when the target property
      repeated, but especially when the motion trajectory suggested that the same
      object had emerged. We show that this same-object benefit is tied to both the
      features and the spatial location of the target. It is most prominent for task
      relevant features, but is weak to absent for task-irrelevant target features or
      for distractors carrying a salient feature. We conclude that attention uses an
      object-specific memory for relevant target information. Finally, we show that
      this object-specific memory is not affected by a change in the exterior
      appearance of the object, but depends on the spatiotemporal history (Experiment
      3).

PMID- 22390296
TI  - Object-based attention overrides perceptual load to modulate visual distraction.
AB  - The ability to ignore task-irrelevant information and overcome distraction is
      central to our ability to efficiently carry out a number of tasks. One factor
      shown to strongly influence distraction is the perceptual load of the task being
      performed; as the perceptual load of task-relevant information processing
      increases, the likelihood that task-irrelevant information will be processed and
      interfere with task performance decreases. However, it has also been demonstrated
      that other attentional factors play an important role in whether or not
      distracting information affects performance. Specifically, object-based attention
      can modulate the extent of distractor processing, leaving open the possibility
      that object-based attention mechanisms may directly modulate the way in which
      perceptual load affects distractor processing. Here, we show that object-based
      attention dominates perceptual load to determine the extent of task-irrelevant
      information processing, with distractors affecting performance only when they are
      contained within the same object as the task-relevant search display. These
      results suggest that object-based attention effects play a central role in
      selective attention regardless of the perceptual load of the task being
      performed.

PMID- 22390297
TI  - Coordinated flexibility: how initial gaze position modulates eye-hand
      coordination and reaching.
AB  - Reaching to targets in space requires the coordination of eye and hand movements.
      In two experiments, we recorded eye and hand kinematics to examine the role of
      gaze position at target onset on eye-hand coordination and reaching performance.
      Experiment 1 showed that with eyes and hand aligned on the same peripheral start
      location, time lags between eye and hand onsets were small and initiation times
      were substantially correlated, suggesting simultaneous control and tight eye-hand
      coupling. With eyes and hand departing from different start locations (gaze
      aligned with the center of the range of possible target positions), time lags
      between eye and hand onsets were large and initiation times were largely
      uncorrelated, suggesting independent control and decoupling of eye and hand
      movements. Furthermore, initial gaze position strongly mediated manual reaching
      performance indexed by increments in movement time as a function of target
      distance. Experiment 2 confirmed the impact of target foveation in modulating the
      effect of target distance on movement time. Our findings reveal the operation of
      an overarching, flexible neural control system that tunes the operation and
      cooperation of saccadic and manual control systems depending on where the eyes
      look at target onset.

PMID- 22390298
TI  - Reducing extrinsic performance-limiting factors in graphene grown by chemical
      vapor deposition.
AB  - Field-effect transistors fabricated on graphene grown by chemical vapor
      deposition (CVD) often exhibit large hysteresis accompanied by low mobility, high
      positive backgate voltage corresponding to the minimum conductivity point
      (V(min)), and high intrinsic carrier concentration (n(0)). In this report, we
      show that the mobility reported to date for CVD graphene devices on SiO(2) is
      limited by trapped water between the graphene and SiO(2) substrate, impurities
      introduced during the transfer process and adsorbates acquired from the ambient.
      We systematically study the origin of the scattering impurities and report on a
      process which achieves the highest mobility (MU) reported to date on large-area
      devices for CVD graphene on SiO(2): maximum mobility (MU(max)) of 7800
      cm(2)/(V.s) measured at room temperature and 12,700 cm(2)/(V.s) at 77 K. These
      mobility values are close to those reported for exfoliated graphene on SiO(2) and
      can be obtained through the careful control of device fabrication steps including
      minimizing resist residue and non-aqueous transfer combined with annealing. It is
      also observed that CVD graphene is prone to adsorption of atmospheric species,
      and annealing at elevated temperature in vacuum helps remove these species.

PMID- 22390299
TI  - The insiders' experiences with continuous transversus abdominis plane blocks for
      analgesia after cesarean delivery.
AB  - OBJECTIVE: Transversus abdominis plane blocks have been recently utilized for
      analgesia after cesarean delivery. However, little data concerning continuous
      transversus abdominis plane blocks has been reported in the existing literature.
      Available studies mainly examine the efficacy of single-injection blocks, and
      only one small case series has been published regarding continuous blocks for
      analgesia after cesarean delivery. First-hand experiences and observations of
      three acute pain medicine specialists who received a continuous transversus
      abdominis plane block for analgesia after cesarean delivery are presented.
      SETTINGS AND PATIENTS: Three physicians specialized in acute and perioperative
      pain medicine personally underwent continuous transversus abdominis plane block
      placements for analgesia after cesarean delivery via a disposable infusion pump
      at the same teaching hospital. RESULTS: In a very motivated, well-supported, and
      informed patient after uncomplicated cesarean delivery, the use of continuous
      transversus abdominis plane blocks for analgesia offers the significant
      advantages of early functional recovery and excellent prolonged analgesia.
      CONCLUSION: The patients experienced postoperative continuous transversus
      abdominis plane blocks that seem to be of value in limiting opiate use and
      improving analgesia with daily activities in the acute postoperative phase after
      cesarean delivery.

PMID- 22390300
TI  - KAI1 suppresses HIF-1alpha and VEGF expression by blocking CDCP1-enhanced Src
      activation in prostate cancer.
AB  - BACKGROUND: KAI1 was initially identified as a metastasis-suppressor gene in
      prostate cancer. It is a member of the tetraspan transmembrane superfamily
      (TM4SF) of membrane glycoproteins. As part of a tetraspanin-enriched microdomain
      (TEM), KAI1 inhibits tumor metastasis by negative regulation of Src. However, the
      underlying regulatory mechanism has not yet been fully elucidated. CUB-domain
      containing protein 1 (CDCP1), which was previously known as tetraspanin
      interacting protein in TEM, promoted metastasis via enhancement of Src activity.
      To better understand how KAI1 is involved in the negative regulation of Src, we
      here examined the function of KAI1 in CDCP1-mediated Src kinase activation and
      the consequences of this process, focusing on HIF-1 alpha and VEGF expression.
      METHODS: We used the human prostate cancer cell line PC3 which was devoid of KAI1
      expression. Vector-transfected cells (PC3-GFP clone #8) and KAI1-expressing PC3
      clones (PC3-KAI1 clone #5 and #6) were picked after stable transfection with KAI1
      cDNA and selection in 800 MUg/ml G418. Protein levels were assessed by
      immunoblotting and VEGF reporter gene activity was measured by assaying
      luciferase activitiy. We followed tumor growth in vivo and immunohistochemistry
      was performed for detection of HIF-1, CDCP1, and VHL protein level. RESULTS: We
      demonstrated that Hypoxia-inducible factor 1alpha (HIF-1alpha) and VEGF
      expression were significantly inhibited by restoration of KAI1 in PC3 cells. In
      response to KAI1 expression, CDCP1-enhanced Src activation was down-regulated and
      the level of von Hippel-Lindau (VHL) protein was significantly increased. In an
      in vivo xenograft model, KAI1 inhibited the expression of CDCP1 and HIF-1alpha.
      CONCLUSIONS: These novel observations may indicate that KAI1 exerts profound
      metastasis-suppressor activity in the tumor malignancy process via inhibition of
      CDCP1-mediated Src activation, followed by VHL-induced HIF-1alpha degradation
      and, ultimately, decreased VEGF expression.

PMID- 22390302
TI  - Kidney graft outcome and quality (after transplantation) from uncontrolled
      deceased donors after cardiac arrest.
AB  - The use of uncontrolled deceased donors after cardiac arrest (uDDCA) has been
      developed in France to compensate for organ shortage. The quality of these
      kidneys remains unclear. We analyzed kidney graft function and histology from 27
      uDDCA and compared them with kidneys from 30 extended criteria donors (ECD) and
      from 24 simultaneous pancreas kidney (SPK) donors as a control group of optimal
      deceased donors. Kidneys from ECD and SPK donors were preserved by static cold
      storage while kidneys from uDDCA were preserved by pulsatile perfusion. The uDDCA
      graft function at 3 years posttransplantation (estimated with MDRD and measured
      with inulin clearance) did not differ from that of the ECD group (eGFR 44.1 vs.
      37.4 mL/min/1.73 m(2) , p = 0.13; mGFR 44.6 vs. 36.1 mL/min/1.73 m(2) , p = 0.07
      in the uDDCA and ECD groups, respectively). The histological assessment of 3
      month and 1-year protocol biopsies did not show differences for interstitial
      lesions between the uDDCA and ECD grafts (IF score at M3 was 30 vs. 28% and at
      M12 36 vs. 33%, p = NS). In conclusion, the results at 3 years with carefully
      selected and machine-perfused uDDCA kidneys have been comparable to ECD kidneys
      and encourage continuation of this program and development of similar programs.

PMID- 22390305
TI  - Testing the effectiveness of two cranial base foramina for metric sex assessment
      of fragmentary remains.
AB  - Sex differences in linear and area dimensions of the foramen ovale and external
      opening of the carotid canal were analyzed in a documented French sample (35 men
      and 32 women). The results demonstrated that a low level of sexual dimorphism is
      present in the cranial base foramina of this sample, with only two-thirds of the
      examined variables exhibiting statistically significant differences (p < 0.05)
      between the sexes. The cross-validated sex classification accuracy rates obtained
      for univariate and multivariate discriminant functions ranged from only 54.7 to
      72.1%. In addition, measurements of the cranial base foramina were found to be
      difficult to record with precision, with intra-observer error percentages ranging
      from 2.35 to 4.23%. Error rates of this magnitude may result in the misallocation
      of specimens. Therefore, osteometric analysis of the foramen ovale and carotid
      canal external opening cannot be recommended as a useful method for cranial sex
      assessment in this population group.

PMID- 22390304
TI  - Blood-feeding ecology of mosquitoes in zoos.
AB  - To determine if the unique host assemblages in zoos influence blood-feeding by
      mosquitoes (Diptera: Culicidae), a sampling programme was conducted in Greenville
      and Riverbanks Zoos, South Carolina, U.S.A., from April 2009 to October 2010. A
      total of 4355 female mosquitoes of 14 species were collected, of which 106
      individuals of nine species were blood-fed. The most common taxa were Aedes
      albopictus (Skuse), Aedes triseriatus (Say), Anopheles punctipennis (Say), Culex
      erraticus (Dyar & Knab), Culex pipiens complex (L.) and Culex restuans
      (Theobald). Molecular analyses (cytochrome b) of bloodmeals revealed that
      mosquitoes fed on captive animals, humans and wildlife, and took mixed
      bloodmeals. Host species included one amphibian, 16 birds, 10 mammals (including
      humans) and two reptiles. Minimum dispersal distances after feeding on captive
      hosts ranged from 15.5 m to 327.0 m. Mosquito-host associations generally
      conformed to previous accounts, indicating that mosquito behaviour inside zoos
      reflects that outside zoos. However, novel variation in host use, including new,
      exotic host records, warrants further investigation. Zoos, thus, can be used as
      experiment environments in which to study mosquito behaviour, and the findings
      extrapolated to non-zoo areas, while providing medical and veterinary benefits to
      zoo animals, employees and patrons.

PMID- 22390303
TI  - Proteomic characterization of the cellular response to nitrosative stress
      mediated by s-nitrosoglutathione reductase inhibition.
AB  - The S-nitrosoglutathione-metabolizing enzyme, GSNO reductase (GSNOR), has emerged
      as an important regulator of protein S-nitrosylation. GSNOR ablation is
      protective in models of asthma and heart failure, raising the idea that GSNOR
      inhibitors might hold therapeutic value. Here, we investigated the effects of a
      small molecule inhibitor of GSNOR (GSNORi) in mouse RAW 264.7 macrophages. We
      found that GSNORi increased protein S-nitrosylation in cytokine-stimulated cells,
      and we utilized stable isotope labeling of amino acids in cell culture (SILAC) to
      quantify the cellular response to this "nitrosative stress". The expression of
      several cytokine-inducible immunomodulators, including osteopontin,
      cyclooxygenase-2, and nitric oxide synthase isoform 2 (NOS2), were decreased by
      GSNORi. In addition, selective targets of the redox-regulated transcription
      factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-including heme
      oxygenase 1 (HO-1) and glutamate cysteine ligase modulatory subunit-were induced
      by GSNORi in a NOS2- and Nrf2-dependent manner. In cytokine-stimulated cells,
      Nrf2 protected from GSNORi-induced glutathione depletion and cytotoxicity and HO
      1 activity was required for down-regulation of NOS2. Interestingly, GSNORi also
      affected a marked increase in NOS2 protein stability. Collectively, these data
      provide the most complete description of the global effects of GSNOR inhibition
      and demonstrate several important mechanisms for inducible response to GSNORi
      mediated nitrosative stress.

PMID- 22390306
TI  - A 14-year-old girl with cough and anemia.

PMID- 22390307
TI  - A 20-month-old boy with fever for 23 days.

PMID- 22390308
TI  - An adolescent girl with weight loss and syncope.

PMID- 22390309
TI  - A 16-month-old with left knee swelling.

PMID- 22390310
TI  - A 14-year-old with joint pain and antinuclear antibodies.

PMID- 22390311
TI  - A 6-year-old girl with new boots.

PMID- 22390312
TI  - Appropriate use of the child developmental review.

PMID- 22390313
TI  - Cytogenetic and molecular predictors of response in patients with myeloid
      malignancies without del[5q] treated with lenalidomide.
AB  - BACKGROUND: While lenalidomide (LEN) shows high efficacy in myelodysplastic
      syndromes (MDS) with del[5q], responses can be also seen in patients presenting
      without del[5q]. We hypothesized that improved detection of chromosomal
      abnormalities with new karyotyping tools may better predict response to LEN.
      DESIGN AND METHODS: We have studied clinical, molecular and cytogenetic features
      of 42 patients with MDS, myeloproliferative neoplasms (MPN), MDS/MPN overlap
      syndromes and secondary acute myeloid leukemia (sAML) without del[5q] by
      metaphase cytogenetics (MC) who underwent therapy with LEN. RESULTS: Fluorescence
      in situ hybridization (FISH) or single nucleotide polymorphism array (SNP-A)
      based karyotyping marginally increased the diagnostic yield over MC, detecting
      2/42 (4.8%) additional cases with del[5q], one of whom were responded to LEN.
      Responses were more often observed in patients with a normal karyotype by MC (60%
      vs abnormal MC; 17%, p = .08) and those with gain of chromosome 8 material by
      either of all 3 karyotyping methods (83% vs all other chromosomal abnormalities;
      44% p = .11). However, 5 out of those 6 patients received combined LEN/AZA
      therapy and it may also suggest those with gain of chromosome 8 material respond
      well to AZA. The addition of FISH or SNP-A did not improve the predictive value
      of normal cytogenetics by MC. Mutational analysis of TET2, UTX, CBL, EZH2, ASXL1,
      TP53, RAS, IDH1/2, and DNMT-3A was performed on 21 of 41 patients, and revealed
      13 mutations in 11 patients, but did not show any molecular markers of
      responsiveness to LEN. CONCLUSIONS: Normal karyotype and gain of chromosome 8
      material was predictive of response to LEN in non-del[5q] patients with myeloid
      malignancies.

PMID- 22390315
TI  - Attributional style among youth at clinical risk for psychosis.
AB  - AIM: A biased attributional style, in which negative events are attributed to
      external and personal causes, is associated with paranoid delusions in
      schizophrenia. It is not known whether this biased attributional style also
      characterizes individuals at clinical risk for psychosis or if it is associated
      with their emergent paranoia. METHODS: Thirty-three clinical high-risk patients
      and 15 age- and gender-similar controls were assessed with the Internal,
      Personal, and Situational Attributions Questionnaire for externalizing and
      personalizing attributional biases and for potential correlates with
      suspiciousness and other symptoms. RESULTS: Both patients and controls had a
      similar external-personalizing attributional style that was unrelated to
      symptoms, including suspiciousness. CONCLUSIONS: Consistent with other studies, a
      biased attributional style was not associated with subthreshold paranoia.
      Therefore, a biased attributional style is likely not a trait that contributes to
      emergent paranoid delusions but is instead a state-dependent correlate of
      paranoid delusions.

PMID- 22390316
TI  - Relevance of sensitization to occupational allergy and asthma in the detergent
      industry.
AB  - There exists considerable historic experience of the relationship between
      exposure and both the induction of sensitization and the elicitation of
      respiratory symptoms from industrial enzymes of bacterial and fungal origin used
      in a wide variety of detergent products. The detergent industry in particular has
      substantial experience of how the control of exposure leads to limitation of
      sensitization with low risk of symptoms. However, the experience also shows that
      there are substantial gaps in knowledge, even when the potential occupational
      allergy problem is firmly under control, and also that the relationship between
      exposure and sensitization can be hard to establish. The latter aspect includes a
      poor appreciation of how peak exposures and low levels of exposure over time
      contribute to sensitization. Furthermore, while a minority of workers develop
      specific IgE, essentially none appear to have symptoms, a situation which appears
      to contradict the allergy dogma that, once sensitized, an individual will react
      to much lower levels of exposure. For enzymes, the expression of symptoms occurs
      at similar or higher levels than those that cause induction. In spite of some
      knowledge gaps, medical surveillance programs and constant air monitoring provide
      the tools for successful management of enzymes in the occupational setting.
      Ultimately, the knowledge gained from the occupational setting facilitates the
      completion of safety assessments for consumer exposure to detergent enzymes. Such
      assessments have been proven to be correct by the decades of safe use both
      occupationally and in consumer products.

PMID- 22390317
TI  - Peptide inhibitors of viral assembly: a novel route to broad-spectrum antivirals.
AB  - We investigated the potential of small peptide segments to function as broad
      spectrum antiviral drug leads. We extracted the alpha-helical peptide segments
      that share common secondary-structure environments in the capsid protein-protein
      interfaces of three unrelated virus classes (PRD1-like, HK97-like, and BTV-like)
      that encompass different levels of pathogenicity to humans, animals, and plants.
      The potential for the binding of these peptides to the individual capsid proteins
      was then investigated using blind docking simulations. Most of the extracted
      alpha-helical peptides were found to interact favorably with one or more of the
      protein-protein interfaces within the capsid in all three classes of virus.
      Moreover, binding of these peptides to the interface regions was found to block
      one or more of the putative "hot spot" regions on the protein interface, thereby
      providing the potential to disrupt virus capsid assembly via competitive
      interaction with other capsid proteins. In particular, binding of the GDFNALSN
      peptide was found to block interface "hot spot" regions in most of the viruses,
      providing a potential lead for broad-spectrum antiviral drug therapy.

PMID- 22390319
TI  - Retraction. Urinary trypsin inhibitor reduced neointimal formation after stent
      implantation in minipig.

PMID- 22390318
TI  - A randomized trial investigating the efficacy and safety of water soluble
      micellar paclitaxel (Paccal Vet) for treatment of nonresectable grade 2 or 3 mast
      cell tumors in dogs.
AB  - BACKGROUND: Effective treatments for dogs with advanced stage mast cell tumors
      (MCT) remain a pressing need. A micellar formulation of paclitaxel (paclitaxel
      [micellar]) has shown promise in early-phase studies. HYPOTHESIS/OBJECTIVES: The
      objective was to demonstrate greater activity for paclitaxel (micellar) compared
      with lomustine. The null hypothesis was MU(p) = MU(L) (ie, proportion of
      responders for the paclitaxel [micellar] and lomustine groups, respectively).
      ANIMALS: Two hundred and fifty-two dogs with advanced stage nonresectable grade 2
      or 3 MCT. METHODS: Prospective multicenter randomized double-blind positive
      controlled clinical trial. The primary endpoint was confirmed overall response
      rate (CORR) at 14 weeks. A secondary endpoint, biologic observed response rate
      (BORR), also was calculated. Safety was assessed by the characterization and
      grading of adverse events (AE). RESULTS: Overall CORR (7% versus 1%; P = .048)
      and BORR (23% versus 10%; P = .012) were greater for paclitaxel (micellar)
      compared with lomustine. Paclitaxel (micellar)-treated dogs were 6.5 times more
      likely to have a confirmed response and 3.1 times more likely to experience a
      biologic observed response. The majority of AE with paclitaxel (micellar) were
      transient and clinically manageable. Twenty-seven dogs (33%) receiving lomustine
      were discontinued because of hepatopathy compared with 3 dogs (2%) receiving
      paclitaxel (micellar) (P < .0001; odds ratio 26.7). CONCLUSIONS AND CLINICAL
      IMPORTANCE: Paclitaxel (micellar)'s activity and safety profile are superior to
      lomustine. The addition of an active and novel taxane to the veterinary
      armamentarium could fill a substantial need and, as its mechanism of action and
      AE profile do not overlap with currently available TKI, its availability could
      lead to effective combination protocols.

PMID- 22390321
TI  - Introduction to the special section on the neural substrate of analogical
      reasoning and metaphor comprehension.
AB  - The special section on the neural substrate of relational reasoning includes 4
      articles that address the processes and brain regions involved in analogical
      reasoning (Green, Kraemer, Fugelsang, Gray, & Dunbar, 2011; Maguire, McClelland,
      Donovan, Tillman, & Krawczyk, 2011) and in metaphor comprehension (Chettih,
      Durgin, & Grodner, 2011; Prat, Mason, & Just, 2011). We see this work as an
      example of how neuroscience approaches to cognition can lead to increased
      understanding of cognitive processes. In this brief introduction, we first
      situate the 4 articles in the context of prior cognitive neuroscience work on
      relational reasoning. We then highlight the main issues explored in these
      articles: different sources of complexity and difficulty in relational
      processing, potential differences between the roles of the 2 hemispheres, and the
      impact of individual differences in various cognitive abilities. The 4 articles
      illustrate a range of methodologies, including functional magnetic resonance
      imaging (fMRI; Green et al., 2011; Prat et al., 2011), event-related potentials
      (ERPs; Maguire et al., 2011), and different types of semantic priming (Chettih et
      al., 2011; Prat et al., 2011). They highlight the connections between research on
      analogy and on metaphor comprehension and suggest, collectively, that a cognitive
      neuroscience approach to relational reasoning can lead to converging conclusions.

PMID- 22390320
TI  - What matters to users of services? An explorative study to promote shared
      decision making in health care.
AB  - BACKGROUND: Involving service users and carers in decisions about their health
      care is a key feature of health-care practice. Professional health and social
      care students need to develop skills and attributes to best enable this to
      happen. AIMS: The aims were to explore service user and carer perceptions of
      behaviours, attributes and context required to enable shared decision making; to
      compare these perceptions to those of students and academic staff with a view to
      utilizing the findings to inform the development of student assessment tools.
      METHODS: A mixed methods approach was used including action learning groups (ALG)
      and an iterative process alongside a modified Delphi survey. PARTICIPANTS: The
      ALGs were from an existing service user and carer network. The survey was sent to
      sixty students, sixty academics and 30 service users from 16 different
      professional disciplines, spanning four Universities in England. RESULTS: The
      collaborative enquiry process and survey identified general agreement that being
      open and honest, listening, showing respect, giving time and being up to date
      were important. The qualitative findings identified that individual
      interpretation was a key factor. An unexpected result was an insight into
      possible insecurities of students. CONCLUSIONS: The findings indicate that
      distilling rich qualitative information into a format for student assessment
      tools could be problematic as the individual context could be lost, it is
      therefore proposed that the information could be better used as a learning rather
      than assessment tool. Several of those involved identified how they valued the
      process and found it beneficial.

PMID- 22390322
TI  - The case for subphonemic attenuation in inner speech: comment on Corley,
      Brocklehurst, and Moat (2011).
AB  - Corley, Brocklehurst, and Moat (2011) recently demonstrated a phonemic similarity
      effect for phonological errors in inner speech, claiming that it contradicted
      Oppenheim and Dell's (2008) characterization of inner speech as lacking
      subphonemic detail (e.g., features). However, finding an effect in both inner and
      overt speech is not the same as finding equal effects in inner and overt speech.
      In this response, I demonstrate that Corley et al.'s data are entirely consistent
      with the notion that inner speech lacks subphonemic detail and that each of their
      experiments exhibits a Similarity * Articulation interaction of about the same
      size that Oppenheim and Dell (2008, 2010) reported in their work. I further show
      that the major discrepancy between the labs' data lies primarily in the magnitude
      of the main effect of phonemic similarity and the overall efficiency of error
      elicitation, and demonstrate that greater similarity effects are associated with
      lower error rates. This leads to the conclusion that successful speech error
      research requires finding a sweet spot between too much randomness and not enough
      data.

PMID- 22390323
TI  - Three tests and three corrections: comment on Koen and Yonelinas (2010).
AB  - The slope of the z-transformed receiver-operating characteristic (zROC) in
      recognition memory experiments is usually less than 1, which has long been
      interpreted to mean that the variance of the target distribution is greater than
      the variance of the lure distribution. The greater variance of the target
      distribution could arise because the different items on a list receive different
      increments in memory strength during study (the "encoding variability"
      hypothesis). In a test of that interpretation, Koen and Yonelinas (2010)
      attempted to further increase encoding variability to see whether it would
      further decrease the slope of the zROC. To do so, they presented items on a list
      for 2 different durations and then mixed the weak and strong targets together.
      After performing 3 tests on the mixed-strength data, Koen and Yonelinas concluded
      that encoding variability does not explain why the slope of the zROC is typically
      less than 1. However, we show that their tests have no bearing on the encoding
      variability account. Instead, they bear on the mixture-unequal-variance signal
      detection (UVSD) model that corresponds to their experimental design. On the
      surface, the results reported by Koen and Yonelinas appear to be inconsistent
      with the predictions of the mixture-UVSD model (though they were taken to be
      inconsistent with the predictions of the encoding variability hypothesis).
      However, all 3 of the tests they performed contained errors. When those errors
      are corrected, the same 3 tests show that their data support, rather than
      contradict, the mixture-UVSD model (but they still have no bearing on the
      encoding variability hypothesis).

PMID- 22390325
TI  - Comfort of wear and material properties of eye patches for amblyopia treatment
      and the influence on compliance.
AB  - BACKGROUND: Occlusion therapy for amblyopia has been the mainstay of treatment
      for centuries, however, acceptance of the patch is often lacking. This study
      evaluated comfort of wear of the eye patch and assessed the mechanical properties
      in order to achieve a more individualized prescription. METHODS: For 8
      consecutive days, parents used each of the four main brands of patches for 2
      consecutive days in a randomized fashion. After 2 days a 21-item questionnaire
      was completed to evaluate comfort of wear for each patch. Compliance was measured
      electronically using the Occlusion Dose Monitor (ODM). In addition, breathing
      capacity at 23 degrees C and 33 degrees C, resistance to water penetration,
      opacity, and strength of adhesion to the skin were measured. RESULTS: Twenty-four
      children participated. Overall, satisfaction was moderate: large differences in
      discomfort when removing the patch, skin reaction, and cosmetic appearance were
      found. In the material measurements large differences were found in opacity and
      strength of adhesion to the skin. In all brands breathing capability was minimal.
      Answers given by the parents matched the physical properties of the eye patch.
      There was no difference in electronically measured compliance between patches.
      CONCLUSIONS: We found large differences in comfort of wear and mechanical
      properties. Therefore, when prescribing a certain brand of patch, the wide
      variety needs to be taken into account. Further study into these properties seems
      warranted; especially breathing capability requires improvement since children
      often wear the patch for a longer period of time. This could contribute to
      increasing satisfaction and consequently may improve compliance.

PMID- 22390326
TI  - Assessing divergence in children with intermittent exotropia.
AB  - PURPOSE: To report fusional divergence in children with intermittent exotropia
      (XT). METHODS: We retrospectively studied 32 children with intermittent XT (aged
      4 to 13 years) and 38 visually normal non-strabismic children. Fusional
      divergence break points were measured using a prism bar, starting from a
      naturally fused state. Distribution of divergence break points was evaluated.
      Subnormal fusional divergence was defined as below the 5th percentile in visually
      normal children. In children with intermittent XT, correlations were calculated
      between divergence break point and control score, angle of deviation, and
      convergence break point. RESULTS: The distribution of fusional divergence break
      points in intermittent XT was normal at near but bimodal at distance. Nine
      percent had subnormal divergence (<10 prism diopters [pd]) at near, and 48% (<6
      pd) at distance. There was a moderate correlation between divergence and
      convergence break points at near (r = 0.44; P=.01) but only weak inverse
      correlations between divergence break point and control score (r = -0.29; P =
      .11) and divergence break point and angle of deviation (r = 0.08; P = . 68) at
      near. CONCLUSIONS: Most children with intermittent XT have normal near fusional
      divergence but nearly half have reduced distance fusional divergence. We found
      the magnitude of near divergence break point correlates with the magnitude of
      near convergence break point. Measuring divergence may provide useful information
      about fragility of fusion in patients with intermittent XT. Future studies of
      fusional divergence are needed to establish whether common measurement methods
      represent true divergence amplitudes and whether such measures have prognostic
      significance.

PMID- 22390327
TI  - Vertical heterophoria and susceptibility to visually induced motion sickness.
AB  - Motion sickness is reported to be a common symptom in patients with vertical
      heterophoria. The goal of this study was to assess the relationship between
      vertical phoria and susceptibility to motion sickness in a nonclinical sample of
      43 subjects. Vertical phoria was measured with a Maddox rod after 30 s of
      occlusion. To evaluate susceptibility to motion sickness, subjects read text
      while sitting inside a rotating optokinetic drum for 10 min. Subjects rated their
      level of motion sickness at 1 min intervals during drum rotation and the
      magnitude of 13 motion sickness symptoms after drum rotation ended. The magnitude
      of vertical phoria ranged from 0 to 2.13 prism diopters (pd) with a mean of 0.46
      pd and correlated significantly with both the maximum rating of motion sickness
      during drum rotation and the summed symptom score following rotation. A vertical
      phoria of 0.75 pd discriminated best between subjects with low vs high summed
      motion sickness symptom scores (p < 0.0001). Introducing a prism to artificially
      increase the phoria of 12 subjects with vertical phorias <0.75 pd increased
      motion sickness symptoms in only 1 subject. Prisms that reduced the phoria of
      subjects with vertical phorias > 0.75 pd reduced motion sickness symptoms in 2 of
      the 4 subjects tested. The results confirm an association between vertical phoria
      and motion sickness, but suggest the relationship may not be causal.

PMID- 22390328
TI  - Botulinum toxin injection into the superior rectus for treatment of strabismus.
AB  - Botulinum toxin injected into the superior rectus (SR) has rarely been described
      in the literature. We conducted a database search to identify all cases of SR
      toxin from 1982 to 2010 at our institution. Out of a total of 7575 patients in
      the database, only eight cases of SR toxin were identified, all of which had
      residual hypertropia following previous ocular surgery. This surgery comprised:
      retinal surgery (3 patients), strabismus surgery for thyroid eye disease (2), and
      transposition for VI nerve palsy (2 patients). In seven out of eight cases, a
      long-lasting mean reduction of 10(Delta) was achieved from between two and three
      injections. Ptosis occurred in all but one case, but resolved. We conclude that
      SR toxin injection has very limited indications, but may be considered in
      residual hypertropia presumed secondary to a tight or overacting SR where the
      patient can tolerate the temporary iatrogenic ptosis.

PMID- 22390329
TI  - Post-vitreoretinal surgery strabismus-a review.
AB  - Vitreoretinal surgery has long been recognized as a significant cause of
      secondary strabismus. These cases can be difficult to manage due to the previous
      surgery and the altered status of the visual function. External scleral buckling
      procedures are most commonly associated with its development; however recent
      research shows that pars plana vitrectomy procedures also have a risk of causing
      the condition. Many factors may play a role in the development of the strabismus:
      mechanical, extraocular muscle changes, local anesthetic administration, and
      sensory alteration. Treatment options include occlusion, prisms, botulinum toxin,
      and surgery. Vitreoretinal surgeons should be aware of the distinct of strabismus
      development following surgery. With increased recognition, the condition can be
      managed more effectively.

PMID- 22390330
TI  - Dissociated vertical divergence.

PMID- 22390333
TI  - The publication of the opticorum Libri sex.

PMID- 22390334
TI  - Occlusion dose monitor available for electronic recording of compliance in patch
      wearing for amblyopia.

PMID- 22390335
TI  - Application of the stressor vulnerability model to understanding posttraumatic
      stress disorder (PTSD) and alcohol-related problems in an undergraduate
      population.
AB  - Research examining the comorbidity of posttraumatic stress disorder (PTSD) and
      alcohol-use disorder (AUD) suggests that individuals experiencing PTSD symptoms
      (PTSS) often drink alcohol as a means to self-medicate their trauma symptoms;
      however, little attention has been given to moderating variables that may make
      this association more likely. The stressor vulnerability model proposes that
      being male, relying on maladaptive forms of coping, and holding positive alcohol
      outcome expectancies predispose individuals to engage in alcohol use when
      experiencing psychological distress. In the current study, sex, avoidance coping
      (AVC), tension-reduction expectancies (TRE), and emotional-relief drinking
      refusal self-efficacy (ERDRSE) were examined as moderators of the relationship
      between PTSS and alcohol-related problems in a sample of 144 undergraduates.
      Results indicated that males reporting high levels of TRE exhibited a stronger
      positive relationship between PTSS and alcohol-related problems than was present
      for males reporting low levels of TRE and for females reporting either high or
      low levels of TRE. In addition, a significant positive relationship between PTSS
      and alcohol-related problems was observed for individuals reporting high levels
      of TRE and low levels of ERDRSE, but not for individuals reporting high levels of
      TRE and high levels of ERDRSE, low TRE-low ERDRSE, or low TRE-high ERDRSE.
      Assessment of these vulnerability factors in traumatized youth and young adults
      may serve as a useful means of identifying individuals at risk for the
      development of alcohol-related problems.

PMID- 22390336
TI  - Predicting alcohol use across adolescence: relative strength of individual,
      family, peer, and contextual risk and protective factors.
AB  - The current study examined developmental changes in the relative influence of
      risk and protective factors (RPFs) across individual, family, peer, school, and
      community domains on adolescent alcohol use. Using longitudinal data from two
      independent samples, multivariate cross-lagged models were used to estimate the
      unique influence of each RPF on subsequent changes in recent alcohol use between
      early to late adolescence. The results supported the hypothesis that the
      influence of Individual Risk would increase during this developmental period.
      However, less consistent evidence was found concerning developmental changes
      among the other domains. Whereas the influence arising from Family Protection
      diminished during adolescence, the influence of Family Risk, School Protection,
      and Community Protection did not vary. The influence of Peer Risk showed a
      nonlinear pattern across adolescence, peaking during the middle adolescent years.
      The results of this study support a developmental approach to adolescent alcohol
      use and emphasize the need for prevention strategies that account for these
      developmental changes.

PMID- 22390337
TI  - Synthesis and properties of 5-cyano-substituted nucleoside analog with a donor
      donor-acceptor hydrogen-bonding pattern.
AB  - 6-Aminopyridin-2-ones form Watson-Crick pairs with complementary purine analogues
      to add a third nucleobase pair to DNA and RNA, if an electron-withdrawing group
      at position 5 slows oxidation and epimerization. In previous work with a
      nucleoside analogue trivially named dZ, the electron withdrawing unit was a nitro
      group. Here, we describe an analogue of dZ (cyano-dZ) having a cyano group
      instead of a nitro group, including its synthesis, pK(a), rates of acid-catalyzed
      epimerization, and enzymatic incorporation.

PMID- 22390339
TI  - Post-trauma inguinal seroma formation in the cat.
AB  - Seven cats presented with large caudoventral abdominal or inguinal swellings
      following road traffic accidents. No case had evidence of disruption to the body
      wall or inguinal ring and the inguinal swellings may have been the result of
      either shear or compressive injury to soft tissues of the inguinum or disruption
      of the regional lymphatics. Six cases resolved completely following strict rest
      or simple Penrose drain placement with no recurrence reported. Recurrence of
      seroma was seen in one case but which then fully resolved following
      omentalisation of the inguinum.

PMID- 22390338
TI  - Nature-inspired total synthesis of (-)-fusarisetin A.
AB  - A concise, protecting group-free total synthesis of (-)-fusarisetin A (1) was
      efficiently achieved in nine steps from commercially available (S)-(-)
      citronellal. The synthetic approach was inspired by our proposed biosynthesis of
      1. Key transformations of our strategy include a facile construction of the
      decalin moiety that is produced via a stereoselective IMDA reaction and a one-pot
      TEMPO-induced radical cyclization/aminolysis that forms the C ring of 1. Our
      route is amenable to analogue synthesis for biological evaluation.

PMID- 22390340
TI  - Perineal descent does not imply a more severe clinical disorder.
AB  - AIM: There is poor consensus in the literature about measuring perineal descent.
      We aimed to assess symptoms and quality of life in constipated patients with
      abnormal perineal descent. METHOD: Constipated patients were categorized into
      those with obstructed defaecation, colonic inertia, mixed disorders and irritable
      bowel syndrome constipation types. Anal physiology was performed. KESS score,
      Irritable Bowel Syndrome Quality of Life and SF-12 questionnaires were completed.
      The position of the perineum was measured by defaecography. Patients were divided
      into two groups according to the position of the perineal descent at rest: group
      1 (normal < 3.5 cm) and group 2 (abnormal > 3.5 cm). RESULTS: Fifty-eight
      patients were identified, 23 (40%) in group 1 and 35 (60%) in group 2. Patients
      in group 2 were older (P = 0.007), had a higher body mass index (BMI; P = 0.003),
      a higher rate of hysterectomy (P = 0.04) and more vaginal deliveries (P = 0.001).
      Obstructed defaecation was the predominant subtype of constipation. Group 1 had
      more difficulty in initiating defaecation and group 2 presented more cases with
      intussusception and enterocele (P = 0.03 for both). Group 2 had a lesser degree
      of perineal descent between rest and straining. Rectal compliance was greater in
      group 2 (P = 0.03). Symptoms and quality of life scores were similar between the
      groups. CONCLUSION: Radiologically determined excessive perineal descent is not
      indicative of worse symptoms or quality of life. This radiological finding does
      not warrant further investigation.

PMID- 22390341
TI  - Sustainability of the whole-community project '10,000 Steps': a longitudinal
      study.
AB  - BACKGROUND: In the dissemination and implementation literature, there is a dearth
      of information on the sustainability of community-wide physical activity (PA)
      programs in general and of the '10,000 Steps' project in particular. This paper
      reports a longitudinal evaluation of organizational and individual sustainability
      indicators of '10,000 Steps'. METHODS: Among project adopters, department heads
      of 24 public services were surveyed 1.5 years after initially reported project
      implementation to assess continuation, institutionalization, sustained
      implementation of intervention components, and adaptations. Barriers and
      facilitators of project sustainability were explored. Citizens (n = 483) living
      near the adopting organizations were interviewed to measure maintenance of PA
      differences between citizens aware and unaware of '10,000 Steps'. Independent
      samples t, Mann-Whitney U, and chi-square tests were used to compare
      organizations for representativeness and individual PA differences. RESULTS: Of
      all organizations, 50% continued '10,000 Steps' (mostly in cycles) and
      continuation was independent of organizational characteristics. Level of
      intervention institutionalization was low to moderate on evaluations of
      routinization and moderate for project saturation. The global implementation
      score (58%) remained stable and three of nine project components were continued
      by less than half of organizations (posters, street signs and variants,
      personalized contact). Considerable independent adaptations of the project were
      reported (e.g. campaign image). Citizens aware of '10,000 Steps' remained more
      active during leisure time than those unaware (227 +/- 235 and 176 +/- 198
      min/week, respectively; t = -2.6; p < .05), and reported more household-related
      (464 +/- 397 and 389 +/- 346 min/week, respectively; t = -2.2; p < .05) and
      moderate-intensity-PA (664 +/- 424 and 586 +/- 408 min/week, respectively; t = 
      2.0; p < .05). Facilitators of project sustainability included an organizational
      leader supporting the project, availability of funding or external support, and
      ready-for-use materials with ample room for adaptation. Barriers included
      insufficient synchronization between regional and community policy levels and
      preference for other PA projects. CONCLUSIONS: '10,000 Steps' could remain
      sustainable but design, organizational, and contextual barriers need
      consideration. Sustainability of '10,000 Steps' in organizations can occur in
      cycles rather than in ongoing projects. Future research should compare
      sustainability other whole-community PA projects with '10,000 Steps' to contrast
      sustainability of alternative models of whole-community PA projects. This would
      allow optimization of project elements and methods to support decisions of choice
      for practitioners.

PMID- 22390344
TI  - Fire retardants abound in baby products: ES&T's top science paper 2011.

PMID- 22390343
TI  - Response to pudendal nerve block in women with pudendal neuralgia.
AB  - OBJECTIVE: To examine the evolution of pain and the duration of numbness after
      neural blockade of the pudendal nerve in women with pudendal neuralgia and
      correlate with clinical and historical data. DESIGN: Prospective, single arm,
      open label study. SETTING: University hospital and outpatient clinic. SUBJECTS:
      Eighty-two adult female patients were recruited from November 8, 2008 to February
      14, 2010. Patients were selected based on the presence of spontaneous or provoked
      pain in the distribution of the pudendal nerve. INTERVENTIONS: Subjects underwent
      a standardized pudendal nerve block. OUTCOME MEASURES: Visual analog pain scores
      and the presence of numbness were recorded before and for 64 hours after the
      pudendal nerve block. A complete clinical history and examination were
      documented. RESULTS: Sixty-six patients completed the study. About 86.9% had a
      reduction in one or more pain symptom, while 44.3% found that more than one of
      their pain symptoms did not return. About 69.7% of patients reported numbness
      lasting up to 16 hours or longer. Previous gynecological surgery was recorded in
      75.8%, previous traumatic obstetric events in 47.0% of cases. Prolonged history
      of pain correlated with a reduced chance of positive outcome of the pudendal
      nerve block. CONCLUSION: In patients with pudendal neuralgia, the pudendal nerve
      block has a variable response, but may have a beneficial effect in a subset of
      women. Surgical and obstetrical trauma are common historical antecedents.

PMID- 22390345
TI  - Temperature dependence of thermal boundary resistances between multiwalled carbon
      nanotubes and some typical counterpart materials.
AB  - We directly measured the temperature dependence of thermal boundary resistances
      (TBRs) between multiwalled carbon nanotubes (MWCNTs) and different materials at
      elevated temperatures. Using the steady-state heat flow and the noncontacted
      measurement method, we could conveniently obtain the TBR-temperature relations.
      Our results indicate that the TBR-temperature relations vary distinctively with
      different contact materials when heating temperatures change from about 300 to
      450 K; that is, the CNT-metal TBRs increase with increasing temperatures, whereas
      the CNT-insulator TBRs decrease. As a comparison, the TBRs between superaligned
      MWCNTs were measured and we found that the CNT-CNT TBRs remain basically
      unchanged as temperatures increase. We also found that the magnitude of TBRs
      between MWCNTs and different materials could differ from each other
      significantly. These results suggest that the choice of the right electrode may
      have an obvious influence on the thermal properties and other properties of the
      CNT-based devices. From another perspective, in view of some existing theoretical
      models about TBRs, our results support the validity of the molecular dynamics
      (MD) simulations in the calculation of CNT-solid TBRs at elevated temperatures.

PMID- 22390342
TI  - Cross-linking measurements of the Potato leafroll virus reveal protein
      interaction topologies required for virion stability, aphid transmission, and
      virus-plant interactions.
AB  - Protein interactions are critical determinants of insect transmission for viruses
      in the family Luteoviridae. Two luteovirid structural proteins, the capsid
      protein (CP) and the readthrough protein (RTP), contain multiple functional
      domains that regulate virus transmission. There is no structural information
      available for these economically important viruses. We used Protein Interaction
      Reporter (PIR) technology, a strategy that uses chemical cross-linking and high
      resolution mass spectrometry, to discover topological features of the Potato
      leafroll virus (PLRV) CP and RTP that are required for the diverse biological
      functions of PLRV virions. Four cross-linked sites were repeatedly detected, one
      linking CP monomers, two within the RTP, and one linking the RTP and CP. Virus
      mutants with triple amino acid deletions immediately adjacent to or encompassing
      the cross-linked sites were defective in virion stability, RTP incorporation into
      the capsid, and aphid transmission. Plants infected with a new, infectious PLRV
      mutant lacking 26 amino acids encompassing a cross-linked site in the RTP
      exhibited a delay in the appearance of systemic infection symptoms. PIR
      technology provided the first structural insights into luteoviruses which are
      crucially lacking and are involved in vector-virus and plant-virus interactions.
      These are the first cross-linking measurements on any infectious, insect
      transmitted virus.

PMID- 22390346
TI  - The long-term outcome of hepatic artery thrombosis after liver transplantation in
      children: role of urgent revascularization.
AB  - Hepatic artery thrombosis (HAT), one of the most severe complications of
      pediatric orthotopic liver transplantation (OLT), often compromises graft and/or
      child survival. Of 590 OLT performed in 516 children over a 20-year period, 45
      were complicated by early HAT, during the first 2 weeks after transplantation.
      Systematic Doppler ultrasonographic detection of HAT allowed successful surgical
      revascularization in 19 instances, resulting in a 20-year graft survival rate of
      77% versus 24% of cases when revascularization was not attempted or failed. A
      combination of surgical emergency revascularization, biliary interventional
      radiology, biliary surgery and/or retransplantation resulted in an 80% 20-year
      patient survival rate, identical to that of transplanted children who did not
      experience early HAT. The majority of long-term survivors with their initial
      graft had normal liver tests, no biliary dilation on ultrasonography and minimal
      or moderate fibrosis on liver histology. A failed attempt at revascularization
      did not significantly alter patient survival. Despite these encouraging results,
      for the children and their parents to overcome the entire process in terms of
      reoperations, repeated radiological interventions, number of hospitalizations and
      emotional stress, remains an ordeal of such magnitude that it justifies renewed
      efforts to progress in the prevention of this complication.

PMID- 22390348
TI  - Upon a failure to equal entry and exit wounds: a possible case of tandem bullets
      in view of the literature.
AB  - Forensic medicine specialists take account of the projectiles remaining in the
      body when determining whether there are an equal number of entry and exit wounds.
      The absence of projectiles should suggest blank cartridges, a single exit wound
      despite several firings and bullet embolization, whereas the presence of more
      projectiles than expected may indicate tandem projectiles and multiple
      projectiles entering through the same hole. Radiological examination of the whole
      body, follow-up of the bullet trajectories, examination of the clothes, and
      examination of the gun and projectiles play a key role in solving difficult
      cases. We review such situations based on a case of tandem bullets. Two 7.65-mm
      bullets created lethal wounds entering through a 32-year-old victim's neck
      followed the same trajectory to a certain point and diverted. We discussed the
      possibilities in cases that show inequalities between entry and exit wounds, in
      light of relevant literature.

PMID- 22390349
TI  - Goettingen Minipigs (GMP): Comparison of Two Different Models for Inducing
      Diabetes.
AB  - PURPOSE: Preclinical experiments on large animals are indispensable for
      evaluating the effectiveness of diabetes therapies. Miniature swine are well
      suited for such studies due to their physiological and pathophysiological
      responses. METHODS: We compare two methods for inducing diabetes in Goettingen
      minipigs (GMP), in five with the beta cell toxin streptozotocin (STZ) and in five
      other GMP by total pancreatectomy (PE). Glucose homeostasis was assessed with the
      intravenous glucose-tolerance test (IVGTT) and continual monitoring of
      interstitial glucose levels. At conclusion of the observation period, the
      pancreata were examined histologically. Three non-diabetic GMP served as control
      group. RESULTS: The IVGTT revealed markedly diabetic profiles in both GMP groups.
      STZ-GMP were found to harbor residual C-peptides and scattered insulin-positive
      cells in the pancreas. PE-GMP survived the total pancreatectomy only with
      intensive postoperative care. CONCLUSIONS: Although both methods reliably induced
      diabetes in GMP, the PE-GMP clearly had more health problems and required a
      greater expenditure of time and resources. The PE-GMP model, however, was better
      at eliminating endogenous insulin and C-peptide than the STZ-GMP model.

PMID- 22390350
TI  - Youth at ultra high risk for psychosis: using the Revised Network Episode Model
      to examine pathways to mental health care.
AB  - AIM: This paper aims to identify the ways in which youth at ultra high risk for
      psychosis access mental health services and the factors that advance or delay
      help seeking, using the Revised Network Episode Model (REV NEM) of mental health
      care. METHODS: A case study approach documents help-seeking pathways,
      encompassing two qualitative interviews with 10 young people and 29 significant
      others. Theoretical propositions derived from the REV NEM are explored,
      consisting of the content, structure and function of the: (i) family; (ii)
      community and school; and (iii) treatment system. RESULTS: Although the aspects
      of the REV NEM are supported and shape pathways to care, we consider rethinking
      the model for help seeking with youth at ultra high risk for psychosis.
      CONCLUSIONS: The pathway concept is important to our understanding of how
      services and supports are received and experienced over time. Understanding this
      process and the strategies that support positive early intervention on the part
      of youth and significant others is critical.

PMID- 22390351
TI  - Pigmented median raphe cyst of the penis.

PMID- 22390352
TI  - Treat the brain; communicate with the mind.

PMID- 22390353
TI  - Oxygen saturation targets for preterm infants in the delivery room.
AB  - Fetal life evolves in a low oxygen milieu as compared to the extra-uterine. In
      the fetal to neonatal transition rapid changes in the oxygen content of the newly
      born infant occur within a brief period of time. Delivery room care givers should
      be aware of the slow transition regarding oxygenation, and supply oxygen as
      needed trying to avoid damage caused by hyper-and-hypoxia. In this regard,
      titrating oxygen inspiratory fraction against oxygen saturation as measured by
      pulse oximetry following recent nomogram ranges is a valid method.

PMID- 22390354
TI  - Implementation of the World Health Organization surgical safety checklist at a
      university hospital in Thailand.
AB  - BACKGROUND: Compliance with the World Health Organization (WHO) surgical safety
      checklist may reduce preventable adverse events. However, compliance may be
      difficult to implement in Thailand. This study was conducted to examine
      compliance with the WHO checklist at a Thai university hospital. METHODS: A
      descriptive study was conducted among 4,340 patients undergoing surgery in nine
      departments from March to August 2009. The compliance rates were computed.
      RESULTS: The highest compliance rate (91.4%) during the sign-in period was with
      patients' confirmation of their identity, operative site, procedure, and consent.
      However, only 19.4% of the surgical sites were marked. In the time-out period,
      surgical teams had introduced themselves by name and role in 79% of the
      operations; and in 95.7% of the cases, the patient's name, the incision site, and
      the procedure had been confirmed. Antibiotic prophylaxis had been given within 60
      min before the incision in 71% of the cases. For 83% of the operations, the
      surgeons reviewed crucial events whereas only 78.4% were reviewed by the
      anesthetists. Sterility had been confirmed by the operating room nurses for every
      patient, but the essential imaging was displayed at a rate of only 64.4%. In the
      sign-out period, nurses correctly confirmed the name of the procedure orally in
      99.5% of the cases. Instrument, sponge, and needle counts were completed and the
      specimen was labeled in most cases, 96.8% and 97.6%, respectively. Equipment
      related problems were identified in 4.4% of the cases, and 100% of them were
      addressed. The surgeon, anesthetist, and nurse reviewed the key concerns for
      recovery and management of the patient at the rate of 85.1%. CONCLUSIONS: The WHO
      checklist can be implemented in a developing country. However, compliance with
      some items was extremely low, reflecting different work patterns and cultural
      norms. Additional education and enforcement of checklist use is needed to improve
      compliance.

PMID- 22390355
TI  - Child development in the context of adversity: experiential canalization of brain
      and behavior.
AB  - The authors examine the effects of poverty-related adversity on child
      development, drawing upon psychobiological principles of experiential
      canalization and the biological embedding of experience. They integrate findings
      from research on stress physiology, neurocognitive function, and self-regulation
      to consider adaptive processes in response to adversity as an aspect of
      children's development. Recent research on early caregiving is paired with
      research in prevention science to provide a reorientation of thinking about the
      ways in which psychosocial and economic adversity are related to continuity in
      human development.

PMID- 22390356
TI  - Evaluation of the use of decision-support software in carcino-embryonic antigen
      (CEA)-based follow-up of patients with colorectal cancer.
AB  - BACKGROUND: The present paper is a first evaluation of the use of "CEAwatch", a
      clinical support software system for surgeons for the follow-up of colorectal
      cancer (CRC) patients. This system gathers Carcino-Embryonic Antigen (CEA) values
      and automatically returns a recommendation based on the latest values. METHODS:
      Consecutive patients receiving follow-up care for CRC fulfilling our in- and
      exclusion criteria were identified to participate in this study. From August
      2008, when the software was introduced, patients were asked to undergo the
      software-supported follow-up. Safety of the follow-up, experiences of working
      with the software, and technical issues were analyzed. RESULTS: 245 patients were
      identified. The software-supported group contained 184 patients; the control
      group contained 61 patients. The software was safe in finding the same amount of
      recurrent disease with fewer outpatient visits, and revealed few technical
      problems. Clinicians experienced a decrease in follow-up workload of up to 50%
      with high adherence to the follow-up scheme. CONCLUSION: CEAwatch is an efficient
      software tool helping clinicians working with large numbers of follow-up
      patients. The number of outpatient visits can safely be reduced, thus
      significantly decreasing workload for clinicians.

PMID- 22390357
TI  - Temperature responses of developmental processes have not been affected by
      breeding in different ecological areas for 17 crop species.
AB  - * Rates of tissue expansion, cell division and progression in the plant cycle are
      driven by temperature, following common Arrhenius-type response curves. * We
      analysed the genetic variability of this response in the range 6-37 degrees C in
      seven to nine lines of maize (Zea mays), rice (Oryza spp.) and wheat (Triticum
      aestivum) and in 18 species (17 crop species, different genotypes) via the meta
      analysis of 72 literature references. * Lines with tropical or north-temperate
      origins had common response curves over the whole range of temperature.
      Conversely, appreciable differences in response curves, including optimum
      temperatures, were observed between species growing in temperate and tropical
      areas. * Therefore, centuries of crop breeding have not impacted on the response
      of development to short-term changes in temperature, whereas evolution over
      millions of years has. This slow evolution may be a result of the need for a
      synchronous shift in the temperature response of all developmental processes,
      otherwise plants will not be viable. Other possibilities are discussed. This
      result has important consequences for the breeding and modelling of temperature
      effects associated with global changes.

PMID- 22390358
TI  - Complete mesocolic excision in colon cancer surgery: a comparison between open
      and laparoscopic approach.
AB  - BACKGROUND: Complete mesocolic excision (CME) with central vessel ligation (CVL)
      as performed in Erlangen offers the best long-term outcome for colon cancer. The
      aim of this study was to assess specimens after laparoscopic vs open CME-CVL
      macroscopically and morphometrically in patients with left and right colon
      cancers. METHOD: All specimens were freshly photographed. Precise tumour
      morphometry and grading of the surgical plane were performed as described by
      pathologists in Leeds, UK. RESULTS: Thirty-four specimens from right-sided
      cancers were divided into 18 transverse colon cancers (nine laparoscopic vs nine
      open) and 16 caecum-ascending colon cancers (seven laparoscopic vs nine open) and
      56 specimens from left-sided cancers (33 laparoscopic vs 23 open). There was no
      difference between laparoscopically and open acquired left- and right-sided
      specimens. Specimens of transverse colon displayed differences in length of
      central ligation to tumour (open 11.67 cm vs laparoscopic 8.72 cm, P = 0.049),
      length of central ligation to bowel wall (open 9.11 cm vs laparoscopic 6.5 cm, P
      = 0.015) and lymph node clearance (open 46.33 vs laparoscopic 39.33, P = 0.033).
      CONCLUSION: Laparoscopy seems to offer specimens of similar quality after CME-CVL
      surgery for colon cancer to the open approach. Issues of completeness of excision
      from laparoscopy are raised for tumours located in the transverse colon.

PMID- 22390359
TI  - Development of NIR fluorescent dyes based on Si-rhodamine for in vivo imaging.
AB  - We have developed a series of novel near-infrared (NIR) wavelength-excitable
      fluorescent dyes, SiR-NIRs, by modifying the Si-rhodamine scaffold to obtain
      emission in the range suitable for in vivo imaging. Among them, SiR680 and SiR700
      showed sufficiently high quantum efficiency in aqueous media. Both antibody-bound
      and free dye exhibited high tolerance to photobleaching in aqueous solution.
      Subcutaneous xenograft tumors were successfully visualized in a mouse tumor model
      using SiR700-labeled anti-tenascin-C (TN-C) antibody, SiR700-RCB1. SiR-NIRs are
      expected to be useful as labeling agents for in vivo imaging studies including
      multicolor imaging, and also as scaffolds for NIR fluorescence probes.

PMID- 22390360
TI  - Antibody-targeted nanovectors for the treatment of brain cancers.
AB  - Introduced here is the hydrophilic carbon clusters (HCCs) antibody drug
      enhancement system (HADES), a methodology for cell-specific drug delivery.
      Antigen-targeted, drug-delivering nanovectors are manufactured by combining
      specific antibodies with drug-loaded poly(ethylene glycol)-HCCs (PEG-HCCs). We
      show that HADES is highly modular, as both the drug and antibody component can be
      varied for selective killing of a range of cultured human primary glioblastoma
      multiforme. Using three different chemotherapeutics and three different
      antibodies, without the need for covalent bonding to the nanovector, we
      demonstrate extreme lethality toward glioma, but minimal toxicity toward human
      astrocytes and neurons.

PMID- 22390361
TI  - Organocatalytic asymmetric 1,4-addition of aldehydes to acridiniums catalyzed by
      a diarylprolinol silyl ether.
AB  - The organocatalytic enantioselective 1,4-addition of aldehydes to acridiniums
      catalyzed by diarylprolinol silyl ether was achieved to furnish chiral acridanes
      in both high yields (82-96%) and excellent enantioselectivities (up to 99% ee),
      which also provides the highly enantioselective intermolecular alpha-alkylation
      of aldehydes with acridiniums salt.

PMID- 22390362
TI  - Chronic migraine-like headache caused by a demyelinating lesion in the brain
      stem.

PMID- 22390363
TI  - Evolution of the content of THC and other major cannabinoids in drug-type
      cannabis cuttings and seedlings during growth of plants.
AB  - In Europe, authorities frequently ask forensic laboratories to analyze seized
      cannabis plants to prove that cultivation was illegal (drug type and not fiber
      type). This is generally done with mature and flowering plants. However,
      authorities are often confronted with very young specimens. The aim of our study
      was to evaluate when the chemotype of cannabis plantlets can be surely determined
      through analysis of eight major cannabinoids content during growth. Drug-type
      seedlings and cuttings were cultivated, sampled each week, and analyzed by high
      performance liquid chromatography with diode array detection. The chemotype of
      clones was recognizable at any developmental stage because of high total Delta(9)
      tetrahydrocannabinol (THC) concentrations even at the start of the cultivation.
      Conversely, right after germination seedlings contained a low total THC content,
      but it increased quickly with plant age up, allowing chemotype determination
      after 3 weeks. In conclusion, it is not necessary to wait for plants' flowering
      to identify drug-type cannabis generally cultivated in Europe.

PMID- 22390364
TI  - Analysis of chimeric ribosomal stalk complexes from eukaryotic and bacterial
      sources: structural features responsible for specificity of translation factors.
AB  - Ribosomal protein P0 forms a pentameric complex with two heterodimers of the
      flexible stalk proteins P1*P2 and plays a role in the functional interaction of
      eukaryotic ribosomes with translational factors. To investigate the functionality
      of domains of P0 characteristic to eukaryotes, we constructed various chimeras
      between silkworm P0 and Escherichia coli counterpart L10. Replacement of the C
      terminal region of L10 with that of P0 allowed the binding of two P1*P2
      heterodimers, which supported ribosomal activity dependent on eukaryotic
      elongation factors eEF-2/eEF-1alpha, but not activity dependent on bacterial
      factors EF-G/EF-Tu. Conversely, replacement of the C-terminal region of P0 with
      that of L10 allowed binding of two bacterial L12 homodimers, which resulted in a
      low level of activity dependent on bacterial factors. Insertion of the extended
      region of P0 that is absent in the bacterial counterpart into L10 did not affect
      L12 binding or bacterial factor-dependent activity, but deletion of this region
      from P0 resulted in a 40% reduction in eukaryotic factor-dependent activity. The
      results indicate that the C-terminal regions of P0 and L10 are responsible for
      binding of the cognate stalk dimers and ribosomal specificity for translation
      factors and suggest that the extended region participates in accessibility only
      for eukaryotic factors.

PMID- 22390365
TI  - Overdose of Vinblastine in place of Vinorelbine during IGEV chemotherapy.
AB  - Any class of drugs is susceptible to errors, in case of antineoplastic agents the
      medication errors may cause severe and life-threatening toxicity due to very
      limited therapeutic index with toxic events even at therapeutic dosage, to
      complexity of regimens and the particular vulnerable population. We report herein
      a case of Vinblastine (VBL) accidental overdose, the cause of mistake, the toxic
      effect and the salvage therapy adopted in a young lady suffering of Hodgkin
      relapse during IGEV chemotherapy.

PMID- 22390367
TI  - Role of solid model simulation surgery for hemifacial microsomia.
AB  - Distraction osteogenesis is now a standard procedure for hemifacial microsomia,
      and various methods have been described. However, it is sometimes difficult to
      obtain the horizontal occlusal plane and facial symmetry. This brief
      communication describes and discusses the usefulness of solid model simulation
      surgery for hemifacial microsomia. 

PMID- 22390368
TI  - Pharmacokinetics and effect of food after oral administration of prolonged
      release tablets of ropinirole hydrochloride in Japanese patients with Parkinson's
      disease.
AB  - WHAT IS KNOWN AND OBJECTIVES: Ropinirole hydrochloride, a dopamine receptor
      agonist with a non-ergot alkaloid structure, is highly selective for the dopamine
      D(2) /D(3) receptors. This study was conducted to evaluate the steady-state
      pharmacokinetics, safety and efficacy after repeated oral administration of
      prolonged-release tablets of ropinirole hydrochloride in the absence of L-dopa
      preparations in Japanese patients with Parkinson's disease (PD). METHODS: This
      was a multicenter, open-label, uncontrolled study. The total duration of
      participation in the study ranged from 56 to 63 weeks. In the study, the plasma
      concentrations of ropinirole, its major metabolite SK&F104557 (N-depropyl
      ropinirole) and another metabolite SK&F89124 (ropinirole hydroxylated at the
      seventh position of the indole ring) were assessed. Safety based on adverse
      events, haematology, biochemistry, urinalysis and electrocardiography (ECG)
      (standard 12-lead ECG) were evaluated, and vital signs (blood pressure/pulse
      rate) were measured. Efficacy based on the Japanese version of Unified
      Parkinson's Disease Rating Scale (UPDRS) Parts III (motor) and II [activities of
      daily living (ADL)] as well as tolerability was evaluated. RESULTS: After
      repeated oral administration of prolonged-release tablets of ropinirole
      hydrochloride in Japanese patients with PD, ropinirole, SK&F104557 and low levels
      of SK&F89124 were detected in plasma. The trough concentrations of ropinirole and
      the two metabolites increased in proportion to the dose when ropinirole
      hydrochloride prolonged-release tablets were administered at doses ranging from 2
      to 16 mg/day. The plasma exposure to ropinirole and its two metabolites after
      intake of normal diet was comparable to that in the fasting state. The most
      common adverse events (10% or more) were somnolence, nausea, constipation,
      hallucination and nasopharyngitis. Most adverse events were mild or moderate in
      severity, and with no death. During the treatment period, serious adverse events
      were reported in five patients. Efficacy analysis (LOCF) at the final endpoint up
      to week 16 demonstrated a mean (SD) change from baseline in the Japanese UPDRS
      III (motor) and II (ADL) scores of -11.3 (8.21) and -3.9 (3.22), respectively,
      and thereafter remained at similar levels until week 52. WHAT IS NEW AND
      CONCLUSIONS: After administration of prolonged-release tablets of ropinirole
      hydrochloride in the absence of L-dopa preparations in Japanese patients with PD,
      the plasma pharmacokinetics of ropinirole and its metabolites was linear and not
      affected by food. Compared with the immediate-release (IR) tablet, the prolonged
      release tablet can be administered to Japanese patients with PD at a reduced
      daily dose frequency and adjusted to the maintenance dose after fewer dose
      changes with a smaller diurnal variation in the plasma ropinirole concentration.

PMID- 22390369
TI  - Differentiating among incretin-based therapies in the management of patients with
      type 2 diabetes mellitus.
AB  - The glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase
      4 (DPP-4) inhibitors have become important options for the management of patients
      with type 2 diabetes mellitus. While the GLP-1R agonists and DPP-4 inhibitors act
      on the incretin system to regulate glucose homeostasis, there are important
      clinical differences among the five agents currently available in the U.S. For
      example, the GLP-1R agonists require subcutaneous administration, produce
      pharmacological levels of GLP-1 activity, promote weight loss, have a more robust
      glucose-lowering effect, and have a higher incidence of adverse gastrointestinal
      effects. In contrast, the DPP-4 inhibitors are taken orally, increase the half
      life of endogenous GLP-1, are weight neutral, and are more commonly associated
      with nasopharyngitis. Differences in efficacy, safety, tolerability, and cost
      among the incretin-based therapies are important to consider in the primary care
      management of patients with type 2 diabetes mellitus.

PMID- 22390370
TI  - The prevalence of leptospiral antibodies in free roaming cats in Worcester
      County, Massachusetts.
AB  - BACKGROUND: Serosurveys of cats for exposure to or infection with leptospires
      have been published from other geographic areas, but none for cats in the United
      States in the past 4 decades. HYPOTHESIS/OBJECTIVES: The purpose of this pilot
      study was to determine the prevalence of leptospiral antibodies in a population
      of free roaming cats in Worcester County, (central) Massachusetts. ANIMALS: Sixty
      three free roaming cats presenting to a trap-neuter-return (TNR) program.
      METHODS: Prospective study. Serum was collected from 63 free roaming cats
      presented to a university associated TNR. Microagglutination titers to Leptospira
      interrogans serovars Autumnalis, Hardjo, Bratislava, Icterohaemorrhagiae,
      Canicola, Pomona, and L kirshneri Grippotyphosa were determined. RESULTS: A total
      of 3 of 63 cats (4.8%) had a titer of 1 : 100 or greater to one or more serovars,
      with Autumnalis being the most common. None of the cats were seropositive to
      Hardjo, Grippotyphosa, or Canicola. CONCLUSIONS AND CLINICAL IMPORTANCE: These
      results are consistent with previously published seroprevalence rates in feral
      cats. Additional studies are required to determine the role of leptosporosis in
      clinical disease in the domestic cat.

PMID- 22390371
TI  - Misinformation and fear of side-effects of family planning.
AB  - Fears about the side-effects from family planning are well-documented barriers to
      use. Many fears are misinformation, while others reflect real experience, and
      understanding of these is not complete. Using qualitative interviews with women
      in three countries, this study examines what women feared, how they acquired this
      knowledge, and how it impacted on decision-making. We aimed to understand whether
      women would be more likely to use family planning if they were counselled that
      the side-effects they feared were inaccurate. Across all countries, respondents
      had a similar host of fears and misinformation about family planning, which were
      comprised of a mixture of personal experience and rumour. Most fears were method
      specific and respondents overwhelmingly stated that they would be more likely to
      use the family planning method they feared if counselled that there were no side
      effects. This suggests programmes should focus on education about family planning
      methods and method mix.

PMID- 22390373
TI  - Cracking the olfactory code of a butterfly: the scent of ageing.
AB  - Although olfaction is a primary mode of communication, its importance in sexual
      selection remains understudied. Here, using the butterfly Bicyclus anynana, we
      address all the parameters of importance to sexual selection for a male olfactory
      signal. We show that variation in the male sex pheromone composition indicates
      male identity and male age. Courting males of different ages display small
      absolute (c. 200 ng) but large relative (100%) change of one specific pheromone
      component (hexadecanal) which, unlike the other components, showed no
      heritability. Females prefer to mate with mid-aged over younger males and the
      pheromone composition is sufficient to determine this preference. Surprisingly
      refined information is thus present in the male olfactory signal and is used for
      sexual selection. Our data also reveal that there may be no 'lek paradox' to
      resolve once the precise signal of importance to females is identified, as
      hexadecanal is, as expected, depleted in additive genetic variation.

PMID- 22390374
TI  - Increased lymph node harvest in patients operated on for right-sided colon
      cancer: a population-based study.
AB  - AIM: In recent decades, the focus has been on the treatment of rectal cancer with
      improved surgical techniques. This has resulted in improved results for patients
      with rectal cancer. Recently, the focus has shifted to colon cancer surgery with
      the introduction of preoperative staging, new surgical techniques, quality
      control and enhanced recovery programmes. The change in operative techniques has
      been most pronounced for patients with tumours on the right side of the colon,
      with more extensive resections and proximal ligations of the vessels. The aim of
      this study was to assess the number of analysed lymph nodes and the metastatic
      index (MI) in patients operated on for right-sided colon cancer in the Stockholm
      area between 1996 and 2009. METHOD: All patients operated on for cancer of the
      right colon between January 1996 and December 2009 were divided into three groups
      based on the year in which they were operated (period 1, 1996-1999; period 2,
      2000-2004; and period 3, 2005-2009). The number of lymph nodes and lymph node
      status were analysed. RESULTS: In total, 3536 patients were operated on for right
      sided colon cancer during the study period. There was a significantly lower
      proportion of emergency operations in the third time period. The mean number of
      lymph nodes examined increased significantly during the overall study period
      (seven in period 1, 11 in period 2 and 18 in period 3; P < 0.001). A significant
      drop in MI was seen during the third time period (0.25, compared with 0.40 in
      period 1 and 0.40 in period 2; P < 0.001). CONCLUSION: During the study period
      there was an increase in the number of analysed lymph nodes and a decrease in MI
      after right-sided hemicolectomies. Further investigations are needed to evaluate
      the potential impact on short-term and long-term outcome.

PMID- 22390375
TI  - Typology of undergraduate nursing students' unsafe clinical practices: Q
      methodology.
AB  - Undergraduate nursing students, as members of the health care team, must uphold
      patient safety as a professional and moral obligation during their clinical
      learning experiences. To address this imperative, in a humanistic paradigm,
      students engage in critical appraisal of self as a developing practitioner. Using
      Q-methodology, this study describes undergraduate nursing students' subjective
      understanding of unsafe clinical practices, and results revealed a typology of
      five groups of unsafe students. The results showed four discrete groups of
      students at risk for unsafe clinical practices-vulnerable, unprepared, unknowing,
      and distanced students. Overall, a consensus viewpoint described the presence of
      the displaced student as the greatest safety risk. Use of this typology as an
      assessment guide may help students and educators cooperatively create and
      maintain a culture of safety while developing competent novice nurses.

PMID- 22390376
TI  - A practical first step to integrating genetics into the curriculum.
AB  - We conducted a systematic literature review to identify tools that could be used
      to measure faculty and undergraduate nursing students' genetic literacy, and we
      assessed the utility of one of those tools, the Genetic Literacy Assessment
      Instrument (GLAI), with faculty and students at a college of nursing in a large
      public university. No significant differences were noted between faculty and
      students in terms of their overall scores on the GLAI. On average, faculty
      answered 76% of the questions correctly and students answered 73% of the
      questions correctly. Both groups scored highest in the genetics and society
      domain (93% and 85% correct answers for faculty and students, respectively) and
      lowest in the evolution domain (52% correct for both groups). The GLAI may be
      used to evaluate curricula for strengths and deficiencies, as well as to identify
      students and faculty in need of additional instruction.

PMID- 22390377
TI  - Stereotyping stigma: undergraduate health students' perceptions at handover.
AB  - The World Health Organization (WHO) has recognized that errors in communication
      are one of the leading causes of adverse patient outcomes. Consequently, the WHO
      developed the High 5s Project to review, among other variables, handover of
      patients between shifts, professionals, and organizations. Seven countries were
      involved in the initial project. Australia responded by using the ISOBAR
      (Identify, Situation, Observations, Background, Agreed plan, and Read-back) tool
      as a template. However, none of the countries involved considered the social and
      emotional effects of handover on the staff or patients, although research has
      demonstrated that attitudes and values can be handed over from one nurse to
      another during this process. This article shows how the nurse who hands over care
      from one shift to the next can transfer stigma and labeling and offers
      suggestions for nurse educators and clinicians to apply national standards and
      core values to clinical practice and education.

PMID- 22390380
TI  - Highly efficient polymer light-emitting diodes using graphene oxide as a hole
      transport layer.
AB  - We present an investigation of polymer light-emitting diodes (PLEDs) with a
      solution-processable graphene oxide (GO) interlayer. The GO layer with a wide
      band gap blocks electron transport from an emissive polymer to an ITO anode while
      reducing the exciton quenching between the GO and the active layer in place of
      poly(styrenesulfonate)-doped poly(3,4-ethylenedioxythiophene) (PEDOT:PSS). This
      GO interlayer maximizes hole-electron recombinations within the emissive layer,
      finally enhancing device performance and efficiency levels in PLEDs. It was found
      that the thickness of the GO layer is an important factor in device performance.
      PLEDs with a 4.3 nm thick GO interlayer are superior to both those with PEDOT:PSS
      layers as well as those with rGO, showing maximum luminance of 39 000 Cd/m(2),
      maximum luminous efficiencies of 19.1 Cd/A (at 6.8 V), and maximum power
      efficiency as high as 11.0 lm/W (at 4.4 V). This indicates that PLEDs with a GO
      layer show a 220% increase in their luminous efficiency and 280% increase in
      their power conversion efficiency compared to PLEDs with PEDOT:PSS.

PMID- 22390378
TI  - The Banff 2009 Working Proposal for polyomavirus nephropathy: a critical
      evaluation of its utility as a determinant of clinical outcome.
AB  - Clinical outcome in BK virus nephropathy (BKVN) was examined in relation to
      clinical and histologic parameters with reference to the Banff Working Proposal
      2009, which emphasizes tubular injury and viral load. Seventy one patients were
      evaluated in three eras: (i) Era-I: No BKV PCR performed (n = 36), (ii) Era-II:
      PCR performed for rising creatinine (n = 24) and (iii) Era III: PCR performed for
      routine screening (n = 11). Six of seventy-one (8.4%) patients were classified as
      Class A, 46/71 (64.8%) as Class B and 19/71 (26.8%) as Class C. Banff class A
      never occurred in Era-I. It is a heterogeneous class that includes biopsies with
      inflammation that have hitherto been included in Class B. Higher inflammation,
      but not tubular injury, nor histologic viral load correlated with worse
      creatinine at 3 months. On long-term follow-up, class C associated with graft
      loss (hazard ratio 2.45, p = 0.03). Clearance of viremia was associated with
      better graft survival at 5 years (46.0% vs. 25.0%). Viruria clearance was
      infrequent (15.6%). In conclusion, the clinical utility of the Banff Working
      Proposal 2009 derives from scoring of fibrosis and not extent of tubular injury
      or viral cytopathic effect. The proposal is not superior to existing schemas that
      include assessment of inflammation, which is a well-known prognostic marker in
      other renal allograft diseases.

PMID- 22390381
TI  - The use of crossover immunoelectrophoresis to detect human blood protein in soil
      from an ambush scene in Kosovo.
AB  - This study examines the survivability of human blood proteins in soils from a
      year and a half old ambush scene in Kosovo. A total of 72 soil samples were
      collected, a number of which were directly associated with bone fragments or
      bullet projectiles. The samples were examined using crossover
      immunoelectrophoresis (CIEP) to determine the presence of blood protein and
      species affiliation. Human blood proteins were identified in 44 of the 72 samples
      (61%) with the majority of the positive observations (29 of 44) found 0.0-4.5 cm
      below ground surface (65%). Chi-squared and two-sample difference of proportions
      tests confirmed significant differences between samples with and without
      associated physical evidence and the presence and depth of human blood proteins.
      While DNA has largely replaced immunological analysis in forensic analyses, our
      results suggest that in particular situations, CIEP may still be a valuable tool
      in criminology.

PMID- 22390382
TI  - Spinal tuberculosis as a cause of low back pain--a timely reminder.

PMID- 22390383
TI  - Hyperglycemic conditions inhibit C3-mediated immunologic control of
      Staphylococcus aureus.
AB  - BACKGROUND: Diabetic patients are at increased risk for bacterial infections;
      these studies provide new insight into the role of the host defense complement
      system in controlling bacterial pathogens in hyperglycemic environments. METHODS:
      The interactions of complement C3 with bacteria in elevated glucose were assayed
      for complement activation to opsonic forms, phagocytosis and bacterial killing.
      C3 was analyzed in euglycemic and hyperglycemic conditions by mass spectrometry
      to measure glycation and structural differences. RESULTS: Elevated glucose
      inhibited S. aureus activation of C3 and deposition of C3b and iC3b on the
      bacterial surface. S. aureus-generated C5a and serum-mediated phagocytosis by
      neutrophils were both decreased in elevated glucose conditions. Interestingly,
      elevated glucose increased the binding of unactivated C3 to S. aureus, which was
      reversible on return to normal glucose concentrations. In a model of
      polymicrobial infection, S. aureus in elevated glucose conditions depleted C3
      from serum resulting in decreased complement-mediated killing of E. coli. To
      investigate the effect of differing glucose concentration on C3 structure and
      glycation, purified C3 incubated with varying glucose concentrations was analyzed
      by mass spectrometry. Glycation was limited to the same three lysine residues in
      both euglycemic and hyperglycemic conditions over one hour, thus glycation could
      not account for observed changes between glucose conditions. However, surface
      labeling of C3 with sulfo-NHS-biotin showed significant changes in the surface
      availability of seven lysine residues in response to increasing glucose
      concentrations. These results suggest that the tertiary structure of C3 changes
      in response to hyperglycemic conditions leading to an altered interaction of C3
      with bacterial pathogens. CONCLUSIONS: These results demonstrate that
      hyperglycemic conditions inhibit C3-mediated complement effectors important in
      the immunological control of S. aureus. Mass spectrometric analysis reveals that
      the glycation state of C3 is the same regardless of glucose concentration over a
      one-hour time period. However, in conditions of elevated glucose C3 appears to
      undergo structural changes.

PMID- 22390384
TI  - Impact of a network system for providing proper inhalation technique by community
      pharmacists.
AB  - OBJECTIVE: The availability of many types of inhalers in the treatment of asthma
      has resulted in a wide range of prescription choices for clinicians. With so many
      devices available, however, there is some confusion regarding their proper use
      among both medical staff and patients. Since 2007, Kitano Hospital and Kita-ku
      Pharmaceutical Association, Osaka, Japan, have provided a network system for
      delivering instruction on correct inhalation technique through community
      pharmacists. We examined the clinical effects of this network system. METHODS:
      Our measurements included the manner in which community pharmacists instruct
      patients with asthma, the frequency of asthma exacerbations, patients' adherence
      to inhalation therapy using a 5-point Likert scale questionnaire, and patients'
      health status both prior to this system and at 4 years after. RESULTS: Usable
      information was obtained from 53 community pharmacists and 146 patients with
      asthma at baseline and from 60 community pharmacists and 148 patients at 4 years.
      When compared with baseline values, significant improvement was found in
      pharmacists' instruction and significant decreases were observed in the frequency
      of asthma exacerbations (1.4 +/- 1.6 vs. 1.0 +/- 1.4 times/yr, p = .042) and
      emergency room visits (0.5 +/- 1.0 vs. 0.2 +/- 0.5 times/yr, p = .004). Adherence
      to the inhalation regimen significantly increased (4.0 +/- 0.7 vs. 4.2 +/- 0.8, p
      = .041), but health status was unchanged. CONCLUSIONS: Our network system may
      improve asthma control and adherence to inhalation regimens.

PMID- 22390385
TI  - Narratives of transactional sex on a university campus.
AB  - Given the imperatives of HIV and gender equality, South African researchers have
      foregrounded transactional sex as a common practice that contributes to unsafe
      and inequitable sexual practices. This paper presents findings from a qualitative
      study with a group of students at a South African university, drawing on
      narratives that speak to the dynamics of reportedly widespread transactional sex
      on campus. Since many of these relationships are inscribed within unequal power
      dynamics across the urban-rural and local-'foreigner' divides, and across
      differences of wealth, age and status that intersect with gender in multiple,
      complex ways, it is argued that these may be exacerbating unsafe and coercive
      sexual practices among this group of young people. The paper further argues for a
      critical, reflexive position on transactional sex, pointing to the way in which
      participants articulate a binaristic response to transactional relationships that
      simultaneously serves to reproduce a silencing of a discourse on female sexual
      desires, alongside a simplistic and deterministic picture of masculinity
      underpinned by the male sexual drive discourse.

PMID- 22390386
TI  - Copy number variation of ribosomal DNA and Pokey transposons in natural
      populations of Daphnia.
AB  - BACKGROUND: Despite their ubiquity and high diversity in eukaryotic genomes, DNA
      transposons are rarely encountered in ribosomal DNA (rDNA). In contrast, R
      elements, a diverse group of non-LTR retrotransposons, specifically target rDNA.
      Pokey is a DNA transposon that targets a specific rDNA site, but also occurs in
      many other genomic locations, unlike R-elements. However, unlike most DNA
      transposons, Pokey has been a stable component of Daphnia genomes for over 100
      million years. Here we use qPCR to estimate the number of 18S and 28S ribosomal
      RNA genes and Pokey elements in rDNA (rPokey), as well as other genomic locations
      (gPokey) in two species of Daphnia. Our goals are to estimate the correlation
      between (1) the number of 18S and 28S rRNA genes, (2) the number of 28S genes and
      rPokey, and (3) the number of rPokey and gPokey. In addition, we ask whether
      Pokey number and distribution in both genomic compartments are affected by
      differences in life history between D. pulex and D. pulicaria. RESULTS: We found
      differences in 18S and 28S gene number within isolates that are too large to be
      explained by experimental variation. In general, Pokey number within isolates is
      modest (< 20), and most are gPokey. There is no correlation between the number of
      rRNA genes and rPokey, or between rPokey and gPokey. However, we identified three
      isolates with unusually high numbers of both rPokey and gPokey, which we infer is
      a consequence of recent transposition. We also detected other rDNA insertions
      (rInserts) that could be degraded Pokey elements, R- elements or the divergent
      PokeyB lineage recently detected in the Daphnia genome sequence. Unlike rPokey,
      rInserts are positively correlated with rRNA genes, suggesting that they are
      amplified by the same mechanisms that amplify rDNA units even though rPokey is
      not. Overall, Pokey frequency and distribution are similar in D. pulex and D.
      pulicaria suggesting that differences in life history have no impact on Pokey.
      CONCLUSIONS: The possibility that many rDNA units do not contain a copy of both
      18S and 28S genes suggests that rDNA is much more complicated than once thought,
      and warrants further study. In addition, the lack of correlation between rPokey,
      gPokey and rDNA unit numbers suggests that Pokey transposition rate is generally
      very low, and that recombination, in combination with natural selection,
      eliminates rPokey much faster than gPokey. Our results suggest that further
      research to determine the mechanisms by which Pokey has escaped complete
      inactivation by its host (the usual fate of DNA transposons), would provide
      important insights into transposon biology.

PMID- 22390387
TI  - Aversive workplace conditions and absenteeism: taking referent group norms and
      supervisor support into account.
AB  - Past research reveals inconsistent findings regarding the association between
      aversive workplace conditions and absenteeism, suggesting that other, contextual
      factors may play a role in this association. Extending contemporary models of
      absence, we draw from the social identity theory of attitude-behavior relations
      to examine how peer absence-related norms and leader support combine to explain
      the effect of aversive workplace conditions on absenteeism. Using a prospective
      design and a random sample of transit workers, we obtained results indicating
      that perceived job hazards and exposure to critical incidents are positively
      related to subsequent absenteeism, but only under conditions of more permissive
      peer absence norms. Moreover, this positive impact of peer norms on absenteeism
      is amplified among employees perceiving their supervisor to be less supportive
      and is attenuated to the point of nonsignificance among those viewing their
      supervisor as more supportive.

PMID- 22390388
TI  - Emotional intelligence, teamwork effectiveness, and job performance: the
      moderating role of job context.
AB  - We advance understanding of the role of ability-based emotional intelligence (EI)
      and its subdimensions in the workplace by examining the mechanisms and context
      based boundary conditions of the EI-performance relationship. Using a trait
      activation framework, we theorize that employees with higher overall EI and
      emotional perception ability exhibit higher teamwork effectiveness (and
      subsequent job performance) when working in job contexts characterized by high
      managerial work demands because such contexts contain salient emotion-based cues
      that activate employees' emotional capabilities. A sample of 212 professionals
      from various organizations and industries indicated support for the salutary
      effect of EI, above and beyond the influence of personality, cognitive ability,
      emotional labor job demands, job complexity, and demographic control variables.
      Theoretical and practical implications of the potential value of EI for workplace
      outcomes under contexts involving managerial complexity are discussed.

PMID- 22390389
TI  - Use of outpatient care in VA and Medicare among disability-eligible and age
      eligible veteran patients.
AB  - BACKGROUND: More than half of veterans who use Veterans Health Administration
      (VA) care are also eligible for Medicare via disability or age, but no prior
      studies have examined variation in use of outpatient services by Medicare
      eligible veterans across health system, type of care or time. OBJECTIVES: To
      examine differences in use of VA and Medicare outpatient services by disability
      eligible or age-eligible veterans among veterans who used VA primary care
      services and were also eligible for Medicare. METHODS: A retrospective cohort
      study of 4,704 disability- and 10,816 age-eligible veterans who used VA primary
      care services in fiscal year (FY) 2000. We tracked their outpatient utilization
      from FY2001 to FY2004 using VA administrative and Medicare claims data. We
      examined utilization differences for primary care, specialty care, and mental
      health outpatient visits using generalized estimating equations. RESULTS: Among
      Medicare-eligible veterans who used VA primary care, disability-eligible veterans
      had more VA primary care visits (p < 0.001) and more VA specialty care visits (p
      < 0.001) than age-eligible veterans. They were more likely to have mental health
      visits in VA (p < 0.01) and Medicare-reimbursed visits (p < 0.01). Disability
      eligible veterans also had more total (VA+Medicare) visits for primary care (p <
      0.01) and specialty care (p < 0.01), controlling for patient characteristics.
      CONCLUSIONS: Greater use of primary care and specialty care visits by disability
      eligible veterans is most likely related to greater health needs not captured by
      the patient characteristics we employed and eligibility for VA care at no cost.
      Outpatient care patterns of disability-eligible veterans may foreshadow care
      patterns of veterans returning from Afghanistan and Iraq wars, who are entering
      the system in growing numbers. This study provides an important baseline for
      future research assessing utilizations among returning veterans who use both VA
      and Medicare systems. Establishing effective care coordination protocols between
      VA and Medicare providers can help ensure efficient use of taxpayer resources and
      high quality care for disabled veterans.

PMID- 22390390
TI  - Health worker attitudes toward peer workers in hepatitis C prevention.
AB  - Attitudes toward people who inject drugs (PWID) and attitudes toward peer workers
      among a cross-section of 101 Australian hepatitis C health workers were assessed.
      A survey consisting of Likert-type questions and one open-ended question
      regarding training was used. Bivariate and regression analyses demonstrated that
      health workers' attitudes toward peer workers were associated with their
      attitudes toward PWID, independent of type of organization or time in the
      hepatitis C sector. Qualitative analysis revealed four training areas suggested
      by health workers for peer workers. Implications of these findings for staff and
      peer training are discussed and future research directions suggested.

PMID- 22390391
TI  - Selective electrocatalytic reduction of CO2 to formate by water-stable iridium
      dihydride pincer complexes.
AB  - Iridium dihydride complexes supported by PCP-type pincer ligands rapidly insert
      CO(2) to yield kappa(2)-formate monohydride products in THF. In
      acetonitrile/water mixtures, these complexes become efficient and selective
      catalysts for electrocatalytic reduction of CO(2) to formate. Electrochemical and
      NMR spectroscopic studies have provided mechanistic details and structures of key
      intermediates.

PMID- 22390393
TI  - Housing stability and recovery among chronically homeless persons with co
      occuring disorders in Washington, DC.
AB  - Pathways Housing First provides access to housing, support, and treatment
      services to clients having the most complex needs-persons who have been homeless
      for at least 5 years and have both a psychiatric disability and substance
      dependency. In a 2-year Housing and Urban Development-funded demonstration
      project in Washington, DC, in 2007 and 2008, we observed promising outcomes in
      housing retention and reductions in psychiatric symptoms, alcohol use, and demand
      for intensive support services. The program is designed to be fiscally self
      sustaining through extant public disability benefits for housing, treatment, and
      support services. This approach shows strong support for first providing a
      permanently supported housing solution for chronically homeless and severely
      disabled individuals in need of housing and treatment of co-occurring disorders.

PMID- 22390396
TI  - First self-perceived signs and symptoms in emerging psychosis compared with
      depression.
AB  - AIM: To investigate differences between the early symptoms of schizophrenia and
      depressive disorders. METHODS: Sixty-one individuals with an at-risk mental state
      (ARMS), 17 of whom later made the transition to psychosis, 37 patients with a
      first episode of psychosis and 16 controls with depressive disorders were
      interviewed about first self-perceived signs and symptoms. RESULTS: In ARMS and
      first episode of psychosis, on average, first self-perceived signs or symptoms
      had occurred about 5-6 years before the interview. In ARMS, including transition
      to psychosis, 'loss of energy' and 'difficulties concentrating' were the most
      frequently recalled first signs. There was much overlap for the four most
      frequently mentioned symptoms in the three groups. As compared with ARMS,
      controls with depressive disorders significantly more often recalled 'depression'
      and 'social isolation' as the very first signs of disease. CONCLUSIONS:
      Clinicians should consider the development of self-recalled first signs over time
      carefully when assessing suspected early prodromal stages of schizophrenia and
      beginning depressive disorder.

PMID- 22390397
TI  - Associations between polymorphisms related to calcium metabolism and human
      height: the Tromso Study.
AB  - A number of single nucleotide polymorphisms (SNPs) related to height have been
      detected. Calcium metabolism is important for the skeleton and accordingly also
      for adult height. Therefore, in the present study, nine SNPs related to the
      vitamin D receptor (VDR) gene and serum levels of 25-hydroxyvitamin D (25(OH)D),
      calcium, phosphate and parathyroid hormone (PTH) were related to height in 9471
      subjects. Relation with height was evaluated with linear regression for trend
      across SNP genotypes with age and gender as covariates. After correcting for
      multiple testing, significant associations with height were found for two SNPs
      related to the VDR gene (rs1544410 (Bsml) and rs7975232 (Apal)), one SNP related
      to serum 25(OH)D (rs3829251 at the DHCR7/NADSYN1 gene), one SNP related to serum
      calcium (rs1459015 at the PTH gene) and one SNP related to serum phosphate
      (rs1697421 at the ALPL gene). For rs3829251, the mean differences in height
      between major and minor homozygotes were 1.5-2.0 cm (P < 0.01) and were seen in
      both genders and all age groups tested, whereas for the other SNPs, the
      differences were less than 1 cm. In conclusion, several SNPs related to calcium
      metabolism are associated with height, in particular rs3829251 at the
      DHCR7/NADSYN1 gene.

PMID- 22390399
TI  - Synthesis and structure-activity analysis of new phosphonium salts with potent
      activity against African trypanosomes.
AB  - A series of 73 bisphosphonium salts and 10 monophosphonium salt derivatives were
      synthesized and tested in vitro against several wild type and resistant lines of
      Trypanosoma brucei (T. b. rhodesiense STIB900, T. b. brucei strain 427, TbAT1-KO,
      and TbB48). More than half of the compounds tested showed a submicromolar EC(50)
      against these parasites. The compounds did not display any cross-resistance to
      existing diamidine therapies, such as pentamidine. In most cases, the compounds
      displayed a good selectivity index versus human cell lines. None of the known T.
      b. brucei drug transporters were required for trypanocidal activity, although
      some of the bisphosphonium compounds inhibited the low affinity pentamidine
      transporter. It was found that phosphonium drugs act slowly to clear a
      trypanosome population but that only a short exposure time is needed for
      irreversible damage to the cells. A comparative molecular field analysis model
      (CoMFA) was generated to gain insights into the SAR of this class of compounds,
      identifying key features for trypanocidal activity.

PMID- 22390400
TI  - The ideal moisturizer: a survey of parental expectations and practice in
      childhood-onset eczema.
AB  - AIM: We evaluated the moisturizing and bathing practices and preferences of
      patients with childhood-onset eczema. METHODS: The attitudes and practice of
      patients with eczema managed at a pediatric dermatology clinic were evaluated,
      using children with non-eczematous skin diseases as controls. Disease severity of
      eczema in the preceding 12 months was evaluated by the Nottingham Eczema Severity
      Score (NESS). Skin hydration (SH) and transepidermal water loss (TEWL) were
      assessed. RESULTS: Majority of patients took shower instead of bath and spent 12
      13 min in shower. Most eczema patients applied emollients after shower/bath. Air
      conditioning use was frequent, and patients with eczema maintained a lower
      ambient temperature than non-eczema patients (p = 0.001). Most eczema patients
      reported regular emollient usage (1.8 times/day for mild vs 2.8 times/day for
      moderate-to-severe eczema, p = 0.001), and acceptability of the current product
      was good to fair. Parents reported that the current emollients were most often
      recommended by doctors. Majority of parents/patients with mild eczema thought an
      ideal emollient needs only to be used twice a day whereas moderate-to-severe
      patients preferred more frequent usage (p = 0.001), and most of them preferred a
      non-fragrant, non-herbal white cream. Agreements concerning ideal emollient usage
      were only "moderate-to-fair" (kappa values <0.61), implying what parents/patients
      practiced was not the same as what they preferred. CONCLUSION: This study helps
      better understand the emolliation practices and preferences of eczema patients.
      Doctors remain the most important source of recommendation. Majority think an
      ideal moisturizer is a non-fragrant, non-herbal, white or transparent cream which
      needs only to be used two to three times per day. Compliance may be enhanced if
      the recommended moisturizer conforms to the parents/patients preference.

PMID- 22390402
TI  - Characterization and inventory of PCDD/F emissions from the ceramic industry in
      China.
AB  - The ceramic industry is considered to be a potential source of dioxins
      (polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), considering the
      widespread distribution of dioxins in kaolinitic clays. Nevertheless, studies on
      the emission of dioxins from the ceramic industry are still very scarce. In this
      study, raw clays and stack gases from six typical ceramic plants in China were
      collected and analyzed to estimate the emission of dioxins from the ceramic
      industry. Dioxin profiles in raw clays were characterized by the domination of
      the congener octachlorodibenzo-p-dioxin (OCDD), and the contents of other
      congeners declined with the decreasing degree of chlorination. During the ceramic
      firing process, a considerable amount (16.5-25.1 wt % of the initial quantity in
      raw clays) of the dioxins was not destroyed and was released to the atmosphere.
      Dechlorination of OCDD generated a broad distribution within the PCDD congeners
      including a variety of non-2,3,7,8-substituted ones with the mass abundance of
      0.4-3.6%. Based on the mean concentrations measured in this study, the inventory
      of PCDD/Fs from the manufacturing of ceramics on the Chinese scale was estimated
      to be 7.94 kg/year; the corresponding value on the I-TEQ basis is 133.6 g I
      TEQ/year. This accounts for about 1.34% (I-TEQ basis) of the total emission of
      dioxins to the environment in China. The results suggest that the ceramic
      industry is a significant source of dioxins in the environment.

PMID- 22390401
TI  - The 4G/4G genotype of the PAI-1 (serpine-1) 4G/5G polymorphism is associated with
      decreased lung allograft utilization.
AB  - Widespread thrombi are found among donor lungs rejected for transplantation. The
      4G/5G polymorphism in the plasminogen activator inhibitor (PAI-1) gene impacts
      transcription and the 4G allele is associated with increased PAI-1 levels. We
      hypothesized that the 4G/4G genotype would be associated with decreased lung
      graft utilization, potentially because of worse oxygenation in the donor. We
      genotyped donors managed by the California Transplant Donor Network from 2001 to
      2008 for the 4G/5G polymorphism in the PAI-1 gene. Non-Hispanic donors from 2001
      to 2005 defined the discovery cohort (n = 519), whereas donors from 2006 to 2008
      defined the validation cohort (n = 369). We found, that the odds of successful
      lung utilization among Non-Hispanic white donors were lower among donors with the
      4G/4G genotype compared to those without this genotype in both the discovery (OR
      = 0.55, 95% CI = 0.3-0.9, p = 0.02) and validation (OR = 0.5, 95% CI = 0.3-0.9, p
      = 0.03) cohorts. This relationship was independent of age, gender, cause of
      death, drug use and history of smoking. Donors with the 4G/4G genotype also had a
      lower PaO2/FiO2 ratio (p = 0.03) and fewer donors with the 4G/4G genotype
      achieved the threshold PaO2/FiO2 ratio >= 300 (p = 0.05). These findings suggest
      a role for impaired fibrinolysis resulting in worse gas exchange and decreased
      donor utilization.

PMID- 22390403
TI  - Enantioselective synthesis of tryptophan derivatives by a tandem Friedel-Crafts
      conjugate addition/asymmetric protonation reaction.
AB  - The tandem Friedel-Crafts conjugate addition/asymmetric protonation reaction
      between 2-substituted indoles and methyl 2-acetamidoacrylate is reported. The
      reaction is catalyzed by (R)-3,3'-dibromo-BINOL in the presence of stoichiometric
      SnCl(4), and is the first example of a tandem conjugate addition/asymmetric
      protonation reaction using a BINOL.SnCl(4) complex as the catalyst. A range of
      indoles furnished synthetic tryptophan derivatives in good yields and high levels
      of enantioselectivity, even on a preparative scale. The convergent nature of this
      transformation should lend itself to the preparation of unnatural tryptophan
      derivatives for use in a broad array of synthetic and biological applications.

PMID- 22390404
TI  - Heterogeneity of cytokeratin 7 expression in pagetoid Bowen's disease.

PMID- 22390405
TI  - Vegetation dynamics as a tool for detecting clandestine graves.
AB  - The burial of a body can affect plant communities through mechanical disturbance
      and nutrient balance alteration. We performed an experimental trial using five
      swine carcasses buried in an open site in Italy. Vegetation dynamics was
      monitored recording monthly every plant individual on a regular sampling grid
      during 1 year on the graves, on an empty control grave, and on an undisturbed
      plot. Plant species composition and cover were significantly different between
      the disturbed and the undisturbed plots. Disturbed plots showed the increase in
      ruderal species and the reduction in stress-tolerant ones. Graves and the control
      grave could not be distinguished from each other. Disturbance was the main factor
      affecting plant cover, while the presence of a buried body did not affect
      vegetation dynamics. However, disturbance could be easily detected; the
      functional approach seems promising for the identification of dynamic patterns to
      be used in different biogeographic and ecological contexts.

PMID- 22390406
TI  - Intraorbital foreign body projectile as a consideration for unilateral pupillary
      defect.
AB  - Intraorbital foreign bodies are frequently the result of high-velocity injuries
      with varying clinical presentations. The resultant diagnosis, management, and
      outcome depend on the type of foreign body present, anatomical location, tissue
      disruption, and symptomatology. A patient who presented to the Emergency
      Department with a large intraorbital foreign body projectile that was not evident
      clinically, but found incidentally on computed tomography and subsequent plain
      films is reported. The emergency room physician needs to be aware of the
      differential diagnosis of a unilateral irregular pupil with or without visual
      acuity changes. The differential diagnosis for any trauma patient with an
      irregular pupil with significant visual loss must include intraorbital foreign
      body and associated injury to the optic nerve directly or via orbital compartment
      syndrome secondary to hemorrhage and/or edema. Patients with significantly
      decreased visual acuity may benefit from emergent surgical intervention. In
      patients with intact visual acuity, the patient must be monitored closely for any
      visual changes as this may require emergent surgical intervention.

PMID- 22390408
TI  - Combining ligand-induced quantum-confined stark effect with type II
      heterojunction bilayer structure in CdTe and CdSe nanocrystal-based solar cells.
AB  - We show that it is possible to combine several charge generation strategies in a
      single device structure, the performance of which benefits from all methods used.
      Exploiting the inherent type II heterojunction between layered structures of CdSe
      and CdTe colloidal quantum dots, we systematically study different ways of
      combining such nanocrystals of different size and surface chemistry and with
      different linking agents in a bilayer solar cell configuration. We demonstrate
      the beneficial use of two distinctly different sizes of NCs not only to improve
      the solar spectrum matching but also to reduce exciton binding energy, allowing
      their efficient dissociation at the interface. We further make use of the ligand
      induced quantum-confined Stark effect in order to enhance charge generation and,
      hence, overall efficiency of nanocrystal-based solar cells.

PMID- 22390407
TI  - The quorum sensing diversity within and between ecotypes of Bacillus subtilis.
AB  - Ecological sociobiology is an emerging field that aims to frame social evolution
      in terms of ecological adaptation. Here we explore the ecological context for
      evolution of quorum sensing diversity in bacteria, where social communication is
      limited to members of the same quorum sensing type (pherotype). We sampled
      isolates of Bacillus subtilis from soil on a microgeographical scale and
      identified three ecologically distinct phylogenetic groups (ecotypes) and three
      pherotypes. Each pherotype was strongly associated with a different ecotype,
      suggesting that it is usually not adaptive for one ecotype to 'listen' to the
      signalling of another. Each ecotype, however, contained one or more minority
      pherotypes shared with the other B. subtilis ecotypes and with more distantly
      related species taxa. The pherotype diversity within ecotypes is consistent with
      two models: first, a pherotype cycling model, whereby minority pherotypes enter a
      population through horizontal genetic transfer and increase in frequency through
      cheating the social interaction; and second, an occasional advantage model, such
      that when two ecotypes are each below their quorum densities, they may benefit
      from listening to one another. This is the first survey of pherotype diversity in
      relation to ecotypes and it will be interesting to further test the hypotheses
      raised and supported here, and to explore other bacterial systems for the role of
      ecological divergence in fostering pherotype diversity.

PMID- 22390409
TI  - Occipital nerve pulsed radiofrequency treatment: a multi-center study evaluating
      predictors of outcome.
AB  - OBJECTIVE: Occipital neuralgia (ON) is a challenging condition for which there is
      no reference standard for treatment. The purpose of this study was to provide
      outcome data on the largest study to date evaluating pulsed radiofrequency (PRF)
      for ON and to determine whether any demographic, clinical, or treatment
      characteristics are associated with success. DESIGN:   Retrospective data
      analysis was conducted in 102 subjects evaluating the effect of myriad factors on
      treatment success. SETTING: This study was conducted in academic civilian and
      military pain treatment centers. PATIENTS: One hundred and two consecutive
      patients with a primary diagnosis of ON were treated with PRF of the greater
      and/or lesser occipital nerve. OUTCOME MEASURES: A positive primary outcome was
      predefined as >=50% pain relief lasting at least 3 months. The secondary outcome
      measure was procedural satisfaction. RESULTS: Fifty-two (51%) patients
      experienced >=50% pain relief and satisfaction with treatment lasting at least 3
      months. Variables associated with a positive outcome included a traumatic
      inciting event (65.7% success rate; P=0.03), lower diagnostic block volumes (odds
      ratio [OR]: 0.72; 95% confidence interval [CI]: 0.62-0.82; P<0.0001), and
      employment of multiple rounds of PRF (OR: 2.95; 95% CI: 1.77-4.92; P<0.0001).
      Factors correlating with treatment failure included extension of pain anterior to
      the scalp apex (OR: 0.32; 95% CI: 0.14-0.73; P=0.006) and ongoing secondary gain
      issues (OR: 0.19; 95% CI: 0.11-0.33; P<0.0001). CONCLUSION: PRF may provide
      intermediate-term benefit in ON to a significant proportion of refractory cases.
      Careful attention to selection criteria and treatment parameters may further
      improve treatment outcomes.

PMID- 22390410
TI  - Mediators of the association of major depressive syndrome and anxiety syndrome
      with postpartum smoking relapse.
AB  - OBJECTIVE: Based on conceptual models of addiction and affect regulation, this
      study examined the mechanisms linking current major depressive syndrome (MDS) and
      anxiety syndrome (AS) to postpartum smoking relapse. METHOD: Data were collected
      in a randomized clinical trial from 251 women who quit smoking during pregnancy.
      Simple and multiple mediation models of the relations of MDS and AS with
      postpartum relapse were examined using linear regression, continuation ratio
      logit models, and a bootstrapping procedure to test the indirect effects.
      RESULTS: Both MDS and AS significantly predicted postpartum smoking relapse.
      After adjusting for MDS, AS significantly predicted relapse. However, after
      adjusting for AS, MDS no longer predicted relapse. Situationally based self
      efficacy, expectancies of controlling negative affect by means other than
      smoking, and various dimensions of primary and secondary tobacco dependence
      individually mediated the effect of both MDS and AS on relapse. In multiple
      mediation models, self-efficacy in negative/affective situations significantly
      mediated the effect of MDS and AS on relapse. CONCLUSIONS: The findings
      underscore the negative impact of depression and anxiety on postpartum smoking
      relapse and suggest that the effects of MDS on postpartum relapse may be largely
      explained by comorbid AS. The current investigation provided mixed support for
      affect regulation models of addiction. Cognitive and tobacco dependence-related
      aspects of negative and positive reinforcement significantly mediated the
      relationship of depression and anxiety with relapse, whereas affect and stress
      did not. The findings emphasize the unique role of low agency with respect to
      abstaining from smoking in negative affective situations as a key predictor of
      postpartum smoking relapse.

PMID- 22390411
TI  - A comparison of approaches for association studies of polymorphisms and
      colorectal cancer risk.
AB  - AIM: Meta-analyses have been used to evaluate associations between polymorphisms
      and colorectal cancer risk, but the quality of individual studies used to inform
      them may vary substantially. Our aim was to apply well-established quality
      control criteria to individual association studies and then compare the results
      of meta-analyses that included or excluded studies that did not meet these
      criteria. METHOD: We used meta-analyses of studies reporting a relationship
      between polymorphisms and colorectal cancer published between 1996 and 2008.
      Polymorphism-cancer associations were derived in separate meta-analyses including
      only those meeting the quality-control criteria. RESULTS: Relative ORs varied
      substantially between the open and restricted group meta-analyses for all
      variants except MTHFR 677 CT. However, the associations were modest and the
      direction of relative risk did not change after applying criteria. Publication
      bias was detected for all associations, except the restricted set of studies for
      GSTP1 GG. CONCLUSION: We observed variation in calculated relative risk and
      changes in tests for publication bias that were dependent on the inclusion
      criteria used for association studies of polymorphisms and colorectal cancer.
      Standardizing study inclusion criteria may reduce the variation in findings for
      meta-analyses of gene-association studies of common diseases such as colorectal
      cancer.

PMID- 22390412
TI  - Tautomeric and conformational properties of benzoylacetone, CH3-C(O)-CH2-C(O)
      C6H5: gas-phase electron diffraction and quantum chemical study.
AB  - Tautomeric and structural properties of benzoylacetone, CH(3)-C(O)-CH(2)-C(O)
      C(6)H(5), have been studied by gas-phase electron diffraction (GED) and quantum
      chemical calculations (B3LYP and MP2 approximation with different basis sets up
      to aug-cc-pVTZ). Analysis of GED intensities resulted in the presence of 100%
      enol tautomer at 331(5) K. The existence of two possible enol conformers in about
      equal amounts is confirmed by both GED and quantum chemical results. In both
      conformers the enol ring possesses C(s) symmetry with a strongly asymmetric
      hydrogen bond. The experimental geometric parameters are reproduced very closely
      by the B3LYP/cc-pVTZ method.

PMID- 22390414
TI  - Content identification of the interdisciplinary assessment of cerebral palsy
      using the International Classification of Functioning, Disability and Health as
      reference.
AB  - PURPOSE: To identify relevant items and most frequents categories related to
      functioning and disability recorded by professionals involved in rehabilitation
      of children with cerebral palsy (CP) and to assess the filling of the records.
      METHODS: A retrospective cross-sectional study based on the written documents
      provided by an interdisciplinary rehabilitation team. Participated in the study
      40 patients with CP, aged 10 months to 17 years. Two raters extracted information
      from the patients' medical documents as recorded by physicians, physiotherapists,
      occupational therapists, speech therapists, social workers, psychologists and
      dieticians using the ICF-CY. Patients' records were scored (+functioning, 
      disability and *environmental factors) using 27 ICF-CY items to assess the
      filling of the records. RESULTS: Eighty-one items in the medical records [body
      structure(15), bodily functions(32), activity(24) and environmental factors(10)]
      were identified as related to the evaluation of the different professions
      involved with neuro-rehabilitation. Physiotherapy and occupational therapy
      provided the most comprehensive assessments performed. Fourteen categories had a
      minimum frequency of 40% during the registration process. CONCLUSIONS: The
      content of the information involves categories related to the structures and body
      functions, activities and environmental factors. The information follows a
      heterogeneous pattern in content and number of categories. The most frequent
      items can comprise a set of codes for triage of CP. It is necessary to establish
      an interdisciplinary consensus based on ICF-CY for systematize the information's
      record.

PMID- 22390415
TI  - Design and synthesis of active site inhibitors of the human farnesyl
      pyrophosphate synthase: apoptosis and inhibition of ERK phosphorylation in
      multiple myeloma cells.
AB  - Human farnesyl pyrophosphate synthase (hFPPS) controls intracellular levels of
      FPP and post-translational prenylation of small GTPase proteins, which are
      essential for cell signaling and cell proliferation. Clinical investigations
      provide evidence that N-BP inhibitors of hFPPS are disease modifying agents that
      improve survival of multiple myeloma (MM) patients via mechanisms unrelated to
      their skeletal effects. A new series of N-BPs was designed that interact with a
      larger portion of the GPP subpocket, as compared to the current therapeutic
      drugs, and rigidify the (364)KRRK(367) tail of hFPPS in the closed conformation
      in the absence of IPP. An analogue of this series was used to demonstrate
      inhibition of the intended biological target, resulting in apoptosis and down
      regulation of ERK phosphorylation in human MM cell lines.

PMID- 22390413
TI  - MGMT promoter methylation in gliomas-assessment by pyrosequencing and
      quantitative methylation-specific PCR.
AB  - BACKGROUND: Methylation of the O(6)-methylguanine-DNA methyltransferase (MGMT)
      gene promoter is a favorable prognostic factor in glioblastoma patients. However,
      reported methylation frequencies vary significantly partly due to lack of
      consensus in the choice of analytical method. METHOD: We examined 35 low- and 99
      high-grade gliomas using quantitative methylation specific PCR (qMSP) and
      pyrosequencing. Gene expression level of MGMT was analyzed by RT-PCR. RESULTS:
      When examined by qMSP, 26% of low-grade and 37% of high-grade gliomas were found
      to be methylated, whereas 97% of low-grade and 55% of high-grade gliomas were
      found methylated by pyrosequencing. The average MGMT gene expression level was
      significantly lower in the group of patients with a methylated promoter
      independent of method used for methylation detection. Primary glioblastoma
      patients with a methylated MGMT promoter (as evaluated by both methylation
      detection methods) had approximately 5 months longer median survival compared to
      patients with an unmethylated promoter (log-rank test; pyrosequencing P = .02,
      qMSP P = .06). One third of the analyzed samples had conflicting methylation
      results when comparing the data from the qMSP and pyrosequencing. The overall
      survival analysis shows that these patients have an intermediate prognosis
      between the groups with concordant MGMT promoter methylation results when
      comparing the two methods. CONCLUSION: In our opinion, MGMT promoter methylation
      analysis gives sufficient prognostic information to merit its inclusion in the
      standard management of patients with high-grade gliomas, and in this study
      pyrosequencing came across as the better analytical method.

PMID- 22390416
TI  - Consenting to health record linkage: evidence from a multi-purpose longitudinal
      survey of a general population.
AB  - BACKGROUND: The British Household Panel Survey (BHPS) is the first long-running
      UK longitudinal survey with a non-medical focus and a sample covering the whole
      age range to have asked for permission to link to a range of administrative
      health records. This study determines whether informed consent led to selection
      bias and reflects on the value of the BHPS linked with health records for
      epidemiological research. METHODS: Multivariate logistical regression is used,
      with whether the respondent gave consent to data linkage or not as the dependent
      variable. Independent variables were entered as four blocks; (i) a set of
      standard demographics likely to be found in most health registration data, (ii) a
      broader set of socio-economic characteristics, (iii) a set of indicators of
      health conditions and (iv) information about the use of health services. RESULTS:
      Participants aged 16-24, males and those living in England were more likely to
      consent. Consent is not biased with respect to socio-economic characteristics or
      health. Recent users of GP services are underrepresented among consenters.
      CONCLUSIONS: Whilst data could only be linked for a minority of BHPS
      participants, the BHPS offers a great range of information on people's life
      histories, their attitudes and behaviours making it an invaluable source for
      epidemiological research.

PMID- 22390417
TI  - GATA transcription factors are involved in IgE-dependent mast cell degranulation
      by enhancing the expression of phospholipase C-gamma1.
AB  - Mast cell degranulation is a dynamic, highly organized process involving numerous
      signaling molecules and enzymes. Although the molecular mechanisms underlying
      antigen-mediated mast cell degranulation have been studied intensively, little is
      known about the transcriptional control of this process. Here, we show that the
      hematopoietic transcription factors GATA1 and GATA2 are involved in mast cell
      degranulation through the control of phospholipase C-gamma1 (PLC-gamma1)
      expression. Knockdown of GATA1 and/or GATA2 by specific siRNA significantly
      reduced antigen-induced degranulation and Ca(2+) mobilization in the rat
      basophilic leukemia cell line RBL-2H3. RT-PCR analyses showed that PLC-gamma1
      expression was significantly decreased by this GATA factor repression. Other GATA
      factor targets, such as the previously reported alpha and beta subunits of the
      high-affinity IgE receptor (FcepsilonRI), were unaffected. Chromatin
      immunoprecipitation and luciferase reporter assays demonstrated that GATA factors
      directly activate PLC-gamma1 gene transcription through a conserved GATA-binding
      motif that resides in the 5'-upstream sequence. Furthermore, we show evidence
      that the PLC-gamma1 expression is regulated by GATA2 in mast cells derived from
      mouse bone marrow. These data indicate that PLC-gamma1 is a target gene of GATA
      factors in mast cells and provide evidence that GATA1 and GATA2 control antigen
      mediated mast cell degranulation by regulating the expression of PLC-gamma1.

PMID- 22390418
TI  - Molecular epidemiology of Cryptosporidium and Giardia in humans on Prince Edward
      Island, Canada: evidence of zoonotic transmission from cattle.
AB  - To determine the zoonotic potential of Cryptosporidium and Giardia in Prince
      Edward Island (PEI), Canada, 658 human faecal specimens were screened that were
      submitted to the Queen Elizabeth Hospital diagnostic laboratory. Overall, 143
      (22%) samples were Cryptosporidium positive, while three (0.5%) were positive for
      Giardia. Successful genotyping of 25 Cryptosporidium isolates by sequence
      analysis of the HSP70 gene revealed that 28 and 72% were C. hominis and C.
      parvum, respectively. Cryptosporidium isolates from humans and previously
      genotyped C. parvum from beef cattle were subtyped by sequence analysis of the
      GP60 gene. Subtyping identified three subtypes belonging to the family IIa. All
      three subtypes IIaA16G2RI (55%), IIaA16G3RI (22%) and IIaA15G2RI (22%) were found
      in the animal isolates, while two of the subtypes found in the animals,
      IIaA16G2RI (80%) and IIaA15G2RI (20%), were also identified in the human
      isolates. Cryptosporidium infection in humans peaked in April-June. Molecular
      epidemiological analysis of the human data showed a C. parvum peak in the spring
      and a relatively smaller peak for C. hominis in July-September. The majority
      (57%) of human Cryptosporidium isolates were found in children between 5 and 10
      years of age. All three Giardia isolates were identified as G. duodenalis
      assemblage A. The overall Cryptosporidium prevalence in our human samples was
      high relative to other studies, but because the samples were submitted to a
      hospital diagnostic laboratory, the results may not be representative of the
      general population. Further, the presence of the same zoonotic C. parvum subtypes
      in cattle and human isolates implies that transmission is largely zoonotic and
      cattle may be a source of sporadic human infections on PEI. The presence of
      Giardia in people on PEI is rare, and the assemblage A found in humans might
      originate from humans, livestock or other domestic or wild animals.

PMID- 22390419
TI  - Strengthening global alliances: the International Society for Animal Clinical
      Pathology.

PMID- 22390420
TI  - Goat anti-human GM-CSF recognizes canine GM-CSF.

PMID- 22390421
TI  - Cytologic subtypes of canine transmissible venereal tumor.

PMID- 22390422
TI  - What's in a stain?

PMID- 22390423
TI  - ASVCP quality assurance guidelines: control of preanalytical and analytical
      factors for hematology for mammalian and nonmammalian species, hemostasis, and
      crossmatching in veterinary laboratories.
AB  - In December 2009, the American Society for Veterinary Clinical Pathology (ASVCP)
      Quality Assurance and Laboratory Standards committee published the updated and
      peer-reviewed ASVCP Quality Assurance Guidelines on the Society's website. These
      guidelines are intended for use by veterinary diagnostic laboratories and
      veterinary research laboratories that are not covered by the US Food and Drug
      Administration Good Laboratory Practice standards (Code of Federal Regulations
      Title 21, Chapter 58). The guidelines have been divided into 3 reports: (1)
      general analytical factors for veterinary laboratory performance and comparisons;
      (2) hematology, hemostasis, and crossmatching; and (3) clinical chemistry,
      cytology, and urinalysis. This particular report is one of 3 reports and provides
      recommendations for control of preanalytical and analytical factors related to
      hematology for mammalian and nonmammalian species, hemostasis testing, and
      crossmatching and is adapted from sections 1.1 and 2.3 (mammalian hematology),
      1.2 and 2.4 (nonmammalian hematology), 1.5 and 2.7 (hemostasis testing), and 1.6
      and 2.8 (crossmatching) of the complete guidelines. These guidelines are not
      intended to be all-inclusive; rather, they provide minimal guidelines for quality
      assurance and quality control for veterinary laboratory testing and a basis for
      laboratories to assess their current practices, determine areas for improvement,
      and guide continuing professional development and education efforts.

PMID- 22390424
TI  - ASVCP quality assurance guidelines: control of preanalytical, analytical, and
      postanalytical factors for urinalysis, cytology, and clinical chemistry in
      veterinary laboratories.
AB  - In December 2009, the American Society for Veterinary Clinical Pathology (ASVCP)
      Quality Assurance and Laboratory Standards committee published the updated and
      peer-reviewed ASVCP Quality Assurance Guidelines on the Society's website. These
      guidelines are intended for use by veterinary diagnostic laboratories and
      veterinary research laboratories that are not covered by the US Food and Drug
      Administration Good Laboratory Practice standards (Code of Federal Regulations
      Title 21, Chapter 58). The guidelines have been divided into 3 reports: (1)
      general analytical factors for veterinary laboratory performance and comparisons;
      (2) hematology, hemostasis, and crossmatching; and (3) clinical chemistry,
      cytology, and urinalysis. This particular report is one of 3 reports and
      documents recommendations for control of preanalytical, analytical, and
      postanalytical factors related to urinalysis, cytology, and clinical chemistry in
      veterinary laboratories and is adapted from sections 1.1 and 2.2 (clinical
      chemistry), 1.3 and 2.5 (urinalysis), 1.4 and 2.6 (cytology), and 3
      (postanalytical factors important in veterinary clinical pathology) of these
      guidelines. These guidelines are not intended to be all-inclusive; rather, they
      provide minimal guidelines for quality assurance and quality control for
      veterinary laboratory testing and a basis for laboratories to assess their
      current practices, determine areas for improvement, and guide continuing
      professional development and education efforts.

PMID- 22390425
TI  - Improving bioscience research reporting: the ARRIVE guidelines for reporting
      animal research.

PMID- 22390428
TI  - Community social norms as social determinants of violence against women.

PMID- 22390431
TI  - Yogi Berra, Ezekiel J. Emanuel, and Millennium Development Goal 7.

PMID- 22390432
TI  - Sanitation and public health: a heritage to remember and continue.

PMID- 22390433
TI  - Appealing to vanity: could potential appearance improvement motivate fruit and
      vegetable consumption?
AB  - Fruit and vegetable consumption is inadequate among adults in the United States;
      this contributes to preventable morbidity and mortality. More effective dietary
      intervention strategies are needed.  Recently, interventions that advertise the
      consequences of behavior for appearance have been successful in modifying sun
      exposure habits and tobacco use. Such an approach might also facilitate dietary
      improvement.  Consumption of carotenoid-rich fruit and vegetables positively
      affects skin color, which influences perceptions of health and attractiveness,
      and promoting such an effect may motivate target audiences to increase
      consumption of this important food group. This approach represents a novel
      direction for the field and is potentially suitable for cost-effective,
      population-level dissemination through the visual media.

PMID- 22390434
TI  - Cross-cultural effects of fruit and vegetable consumption on skin color.

PMID- 22390435
TI  - Protecting young people from junk food advertising: implications of psychological
      research for First Amendment law.
AB  - In the United States, one third of children and adolescents are overweight or
      obese, yet food and beverage companies continue to target them with advertising
      for products that contribute to this obesity crisis.  When government
      restrictions on such advertising are proposed, the constitutional commercial
      speech doctrine is often invoked as a barrier to action. We explore incongruities
      between the legal justifications for the commercial speech doctrine and the
      psychological research on how food advertising affects young people.  A proper
      interpretation of the First Amendment should leave room for regulations to
      protect young people from advertising featuring calorie-dense, nutrient-poor
      foods and beverages.

PMID- 22390436
TI  - Policy instruments used by States seeking to improve school food environments.
AB  - US legislatures and program administrators have sought to control the sale of
      foods offered outside of federally funded meal programs in schools, but little is
      known about which policies, if any, will prevent obesity in children.  We used a
      theoretical policy science typology to understand the types of policy instruments
      used by US state governments from 2001 to 2006. We coded 126 enacted bills and
      observed several types of instruments prescribed by state legislatures to
      influence the foods sold in schools and improve the school food environment.  Our
      study helps to better understand the various instruments used by policymakers and
      sets the stage to examine the effectiveness of the policy instruments used to
      prevent obesity.

PMID- 22390437
TI  - The impact of the individual mandate and Internal Revenue Service Form 990
      Schedule H on community benefits from nonprofit hospitals.
AB  - In response to a growing concern that nonprofit hospitals are not providing
      sufficient benefit to their communities in return for their tax-exempt status,
      the Internal Revenue Service (IRS) now requires nonprofit hospitals to formally
      document the extent of their community contributions.  While the IRS is
      increasing financial scrutiny of nonprofit hospitals, many provisions in the
      recently passed historical health reform legislation will also have a significant
      impact on the provision of uncompensated care and other community benefits.  We
      argue that health reform does not render the nonprofit organizational form
      obsolete. Rather, health reform should strengthen the nonprofit hospitals'
      ability to fulfill their missions by better targeting subsidies for uncompensated
      care and potentially increasing subsidized health services provision, many of
      which affect the public's health.

PMID- 22390438
TI  - Public health department accreditation implementation: transforming public health
      department performance.
AB  - In response to a call for improved quality and consistency in public health
      departments, the Public Health Accreditation Board (PHAB) is leading a voluntary
      public health accreditation initiative in the United States.  The public health
      department accreditation system will implement a comprehensive set of standards
      that set uniform performance expectations for health departments to provide the
      services necessary to keep communities healthy. Continuous quality improvement is
      a major component of PHAB accreditation, demonstrating a commitment to empower
      and encourage public health departments to continuously improve their
      performance.  The accreditation process was tested in 30 health departments
      around the country in 2009 and 2010, and was launched on a national level in
      September 2011 at the National Press Club in Washington, DC.

PMID- 22390439
TI  - Conflicts of quarantine the case of Jewish immigrants to the Jewish state.
AB  - Shaar Haaliya--Israel's Ellis Island during the mass immigration of the 1950s--is
      a case study that challenges the historian's understanding of the concept of
      quarantine. It was isolated and fenced off for declared health purposes and was
      widely referred to as a quarantine, but archival and historiographical
      documentation suggest that Israeli public health policy did not define it as
      such. I track the discussion and conflict surrounding Shaar Haaliya's function
      and perception as a quarantine. This is a story that illuminates the way fear of
      disease converged with fear of immigration as well as the way defiance of public
      health institutions took shape in a unique framework of citizenship and during a
      unique wave of migration.

PMID- 22390440
TI  - Identifying unaddressed systemic health conditions at dental visits: patients who
      visited dental practices but not general health care providers in 2008.
AB  - We assessed the proportion and characteristics of patients who do not regularly
      visit general health care providers but do visit dentists and whose unaddressed
      systemic health conditions could therefore be identified by their dentist. Of the
      26.0% of children and 24.1% of adults that did not access general outpatient
      health care in 2008, 34.7% and 23.1%, respectively, visited a dentist. They
      varied by census region, family income, and sociodemographics. Dental practices
      can serve as alternate sites of opportunity to identify health concerns among
      diverse groups of US patients.

PMID- 22390441
TI  - Framing water, sanitation, and hygiene needs among female-headed households in
      Periurban Maputo, Mozambique.
AB  - OBJECTIVES: Water, sanitation, and hygiene challenges in the global south require
      analyses that capture more than urban-rural differences. A new taxonomy is
      required to help systematize and respond to basic sanitary needs. My aim was to
      test a new framework for understanding these concerns in periurban spaces.
      METHODS: I conducted semistructured qualitative interviews with a randomized
      sample, stratified by settlement density, of mostly female-headed households in
      KaTembe, the largest municipal district of Maputo, Mozambique. The survey
      included questions on the adequacy, accessibility, and affordability of water,
      sanitation facilities, and waste management as well as awareness of illnesses and
      safe hygiene practices. RESULTS: Despite being part of a capital city, KaTembe
      residents face a diverse mixture of sanitary challenges, as revealed through an
      analysis of adequacy, accessibility, affordability, and awareness issues. The
      interaction of these 4 lenses provides insight into residents' behaviors and the
      obstacles they face in securing adequate provisions. CONCLUSIONS: International
      water, sanitation, and hygiene studies continue to depend on urban-rural
      distinctions. However, an adequacy, accessibility, affordability, and awareness
      framework can improve the utility of their data.

PMID- 22390442
TI  - Effect of same-sex marriage laws on health care use and expenditures in sexual
      minority men: a quasi-natural experiment.
AB  - OBJECTIVES: We sought to determine whether health care use and expenditures among
      gay and bisexual men were reduced following the enactment of same-sex marriage
      laws in Massachusetts in 2003. METHODS: We used quasi-experimental, prospective
      data from 1211 sexual minority male patients in a community-based health center
      in Massachusetts. RESULTS: In the 12 months after the legalization of same-sex
      marriage, sexual minority men had a statistically significant decrease in medical
      care visits (mean = 5.00 vs mean = 4.67; P = .05; Cohen's d = 0.17), mental
      health care visits (mean = 24.72 vs mean = 22.20; P = .03; Cohen's d = 0.35), and
      mental health care costs (mean = $2442.28 vs mean = $2137.38; P = .01; Cohen's d
      = 0.41), compared with the 12 months before the law change. These effects were
      not modified by partnership status, indicating that the health effect of same-sex
      marriage laws was similar for partnered and nonpartnered men. CONCLUSIONS:
      Policies that confer protections to same-sex couples may be effective in reducing
      health care use and costs among sexual minority men.

PMID- 22390443
TI  - Adult health behaviors over the life course by sexual orientation.
AB  - OBJECTIVES: We estimated differences in health behaviors among adults by sexual
      orientation. METHODS: We pooled 4 years of data (2001, 2003, 2005, and 2007) from
      the California Health Interview Survey. We estimated the frequency of smoking,
      alcohol use, healthy dietary behaviors, physical activity, and health care
      utilization, and we used logistic regression modeling to determine the odds of
      each behavior with increasing age and for 2 age groups: younger than 50 years and
      50 years old or older. RESULTS: At any adult age, lesbians had greater odds of
      smoking and binge drinking than did heterosexual women, and gay and bisexual men
      had greater health care utilization than did heterosexual men. Other risk
      behaviors differed with age. CONCLUSIONS: Some behavioral change interventions
      should target lesbians, gays, and bisexuals at all ages, whereas other
      interventions should specifically target individuals at younger ages.

PMID- 22390444
TI  - The costs of treating American Indian adults with diabetes within the Indian
      Health Service.
AB  - OBJECTIVES: We examined the costs of treating American Indian adults with
      diabetes within the Indian Health Service (IHS). METHODS: We extracted
      demographic and health service utilization data from the IHS electronic medical
      reporting system for 32 052 American Indian adults in central Arizona in 2004 and
      2005. We derived treatment cost estimates from an IHS facility-specific cost
      report. We examined chronic condition prevalence, medical service utilization,
      and treatment costs for American Indians with and without diabetes. RESULTS: IHS
      treatment costs for the 10.9% of American Indian adults with diabetes accounted
      for 37.0% of all adult treatment costs. Persons with diabetes accounted for
      nearly half of all hospital days (excluding days for obstetrical care). Hospital
      inpatient service costs for those with diabetes accounted for 32.2% of all costs.
      CONCLUSIONS: In this first study of treatment costs within the IHS, costs for
      American Indians with diabetes were found to consume a significant proportion of
      IHS resources. The findings give federal agencies and tribes critical information
      for resource allocation and policy formulation to reduce and eventually eliminate
      diabetes-related disparities between American Indians and Alaska Natives and
      other racial/ethnic populations.

PMID- 22390445
TI  - Individual participant data meta-analysis of mechanical workplace risk factors
      and low back pain.
AB  - OBJECTIVES: We used individual participant data from multiple studies to conduct
      a comprehensive meta-analysis of mechanical exposures in the workplace and low
      back pain. METHODS: We conducted a systematic literature search and contacted an
      author of each study to request their individual participant data. Because
      outcome definitions and exposure measures were not uniform across studies, we
      conducted 2 substudies: (1) to identify sets of outcome definitions that could be
      combined in a meta-analysis and (2) to develop methods to translate mechanical
      exposure onto a common metric. We used generalized estimating equation regression
      to analyze the data. RESULTS: The odds ratios (ORs) for posture exposures ranged
      from 1.1 to 2.0. Force exposure ORs ranged from 1.4 to 2.1. The magnitudes of the
      ORs differed according to the definition of low back pain, and heterogeneity was
      associated with both study-level and individual-level characteristics.
      CONCLUSIONS: We found small to moderate ORs for the association of mechanical
      exposures and low back pain, although the relationships were complex. The
      presence of individual-level OR modifiers in such an area can be best understood
      by conducting a meta-analysis of individual participant data.

PMID- 22390446
TI  - Racial and ethnic disparities in depression care in community-dwelling elderly in
      the United States.
AB  - OBJECTIVES: We investigated racial/ethnic disparities in the diagnosis and
      treatment of depression among community-dwelling elderly. METHODS: We performed a
      secondary analysis of Medicare Current Beneficiary Survey data (n = 33,708) for
      2001 through 2005. We estimated logistic regression models to assess the
      association of race/ethnicity with the probability of being diagnosed and treated
      for depression with either antidepressant medication or psychotherapy. RESULTS:
      Depression diagnosis rates were 6.4% for non-Hispanic Whites, 4.2% for African
      Americans, 7.2% for Hispanics, and 3.8% for others. After we adjusted for a range
      of covariates including a 2-item depression screener, we found that African
      Americans were significantly less likely to receive a depression diagnosis from a
      health care provider (adjusted odds ratio [AOR] = 0.53; 95% confidence interval
      [CI] = 0.41, 0.69) than were non-Hispanic Whites; those diagnosed were less
      likely to be treated for depression (AOR = 0.45; 95% CI = 0.30, 0.66).
      CONCLUSIONS: Among elderly Medicare beneficiaries, significant racial/ethnic
      differences exist in the diagnosis and treatment of depression. Vigorous clinical
      and public health initiatives are needed to address this persisting disparity in
      care.

PMID- 22390447
TI  - Reduction in purchases of sugar-sweetened beverages among low-income Black
      adolescents after exposure to caloric information.
AB  - OBJECTIVES: We examined the effect of an intervention to provide caloric
      information about sugar-sweetened beverages (SSBs) on the number of SSB
      purchases. METHODS: We used a case-crossover design with 4 corner stores located
      in low-income, predominately Black neighborhoods in Baltimore, Maryland. The
      intervention randomly posted 1 of 3 signs with the following caloric information:
      (1) absolute caloric count, (2) percentage of total recommended daily intake, and
      (3) physical activity equivalent. We collected data for 1600 beverage sales by
      Black adolescents, aged 12-18 years, including 400 during a baseline period and
      400 for each of the 3 caloric condition interventions. RESULTS: Providing Black
      adolescents with any caloric information significantly reduced the odds of SSB
      purchases relative to the baseline (odds ratio [OR] = 0.56; 95% confidence
      interval [CI] = 0.36, 0.89). When examining the 3 caloric conditions separately,
      the significant effect was observed when caloric information was provided as a
      physical activity equivalent (OR = 0.51; 95% CI = 0.31, 0.85). CONCLUSIONS:
      Providing easily understandable caloric information--particularly a physical
      activity equivalent--may reduce calorie intake from SSBs among low-income, Black
      adolescents.

PMID- 22390448
TI  - Outcomes of a Latino community-based intervention for the prevention of diabetes:
      the Lawrence Latino Diabetes Prevention Project.
AB  - OBJECTIVES: We tested the effectiveness of a community-based, literacy-sensitive,
      and culturally tailored lifestyle intervention on weight loss and diabetes risk
      reduction among low-income, Spanish-speaking Latinos at increased diabetes risk.
      METHODS: Three hundred twelve participants from Lawrence, Massachusetts, were
      randomly assigned to lifestyle intervention care (IC) or usual care (UC) between
      2004 and 2007. The intervention was implemented by trained Spanish-speaking
      individuals from the community. Each participant was followed for 1 year.
      RESULTS: The participants' mean age was 52 years; 59% had less than a high school
      education. The 1-year retention rate was 94%. Compared with the UC group, the IC
      group had a modest but significant weight reduction (-2.5 vs 0.63 lb; P = .04)
      and a clinically meaningful reduction in hemoglobin A1c (-0.10% vs -0.04%; P =
      .009). Likewise, insulin resistance improved significantly in the IC compared
      with the UC group. The IC group also had greater reductions in percentage of
      calories from total and saturated fat. CONCLUSIONS: We developed an inexpensive,
      culturally sensitive diabetes prevention program that resulted in weight loss,
      improved HbA1c, and improved insulin resistance in a high-risk Latino population.

PMID- 22390449
TI  - Social norms, collective efficacy, and smoking cessation in urban neighborhoods.
AB  - OBJECTIVES: We examined the separate and combined relations of neighborhood-level
      social norms and collective efficacy with individuals' cigarette smoking
      cessation. METHODS: We modeled the hazard of quitting over a 5-year period among
      863 smokers who participated in the 2005 New York Social Environment Study.
      RESULTS: In adjusted Cox proportional hazard models, prohibitive neighborhood
      smoking norms were significantly associated with higher rates of smoking
      cessation (second quartile hazard ratio [HR] = 1.17; 95% confidence interval [CI]
      = 0.59, 2.32; third quartile HR = 2.37; 95% CI = 1.17, 4.78; fourth quartile HR =
      1.80; 95% CI = 0.85, 3.81). We did not find a significant association between
      neighborhood collective efficacy and cessation or significant evidence of a joint
      relation of collective efficacy and smoking norms with cessation. CONCLUSIONS:
      Neighborhood social norms may be more relevant than is collective efficacy to
      smoking cessation. The normative environment may shape health behavior and should
      be considered as part of public health intervention efforts.

PMID- 22390450
TI  - The impact of changes in job strain and its components on the risk of depression.
AB  - OBJECTIVES: We assessed the impact of changes in dimensions of the psychosocial
      work environment on risk of depression in a longitudinal cohort of Canadian
      workers who were free of depression when work conditions were initially reported.
      METHODS: Using a sample (n = 3735) from the Canadian National Population Health
      Survey, we examined the effects of changes in job control, psychological demands,
      and social support over a 2-year period on subsequent depression. We adjusted
      models for a number of covariates, including personal history of depression.
      RESULTS: Respondents with increased psychological demands were more likely to
      have depression over the following 2 years (odds ratio = 2.36; 95% confidence
      interval = 1.14, 4.88). This risk remained statistically significant after
      adjustment for age, gender, marital status, presence of children, level of
      education, chronic health conditions, subclinical depression when work conditions
      were initially assessed, family history of depression, and personal history of
      depression. CONCLUSIONS: These results demonstrate that changes in psychological
      demands have a stronger influence than changes in job control on the onset of
      depression, highlighting the importance of not assuming an interaction between
      these 2 components of job strain when assessing health outcomes.

PMID- 22390451
TI  - Determinants of and disparities in reproductive health service use among
      adolescent and young adult women in the United States, 2002-2008.
AB  - OBJECTIVES: We investigated determinants of and disparities in reproductive
      health service use among young women in the United States from 2002 to 2008.
      METHODS: Using data on 4421 US women aged 15 to 24 years from the National Survey
      of Family Growth (2002, n = 2157; 2006-2008, n = 2264), we employed descriptive
      and univariate statistics and multivariate regression models to examine service
      use across women's sociodemographic and reproductive characteristics and to
      investigate potential disparate changes in service use over time. RESULTS: More
      than half the sample (59%) had used services in the past year. In regression
      models, predictors of service use included age, education, birthplace, insurance,
      religious participation, mother's education, childhood family situation, age at
      menarche, sexual intercourse experience, recent number of partners, and previous
      gynecological diagnosis. Although service use decreased by 8% overall from 2002
      to 2006-2008 (P < .001), the magnitude of decline was similar across demographic
      and socioeconomic groups. CONCLUSIONS: Inequalities in reproductive health
      service use exist among women in the United States, particularly among the
      youngest and socially disadvantaged women, which may translate to poor and
      disparate reproductive outcomes. Public health and policy strategies are needed
      to eliminate inequities in reproductive health service.

PMID- 22390454
TI  - Sexuality and homelessness in Los Angeles public schools.

PMID- 22390456
TI  - A curriculum for the new dental practitioner: preparing dentists for a
      prospective oral health care environment.
AB  - The emerging concept of prospective health care would shift the focus of health
      care from disease management to disease prevention and health management. 
      Dentistry has a unique opportunity to embrace this model of prospective and
      collaborative care and focus on the management of oral health.  Academic
      dentistry must better prepare future dentists to succeed in this new health care
      environment by providing them with the scientific and technical knowledge
      required to understand and assess risk and practice disease prevention. Dental
      schools must consider creating career pathways for enabling future graduates to
      assume important leadership roles that will advance a prospective oral health
      care system.

PMID- 22390457
TI  - Text4Health: impact of text message reminder-recalls for pediatric and adolescent
      immunizations.
AB  - OBJECTIVES: We conducted 2 studies to determine the impact of text message
      immunization reminder-recalls in an urban, low-income population. METHODS: In 1
      study, text message immunization reminders were sent to a random sample of
      parents (n = 195) whose children aged 11 to 18 years needed either or both
      meningococcal (MCV4) and tetanus-diphtheria-acellular pertussis (Tdap)
      immunizations. We compared receipt of MCV4 or Tdap at 4, 12, and 24 weeks with
      age- and gender-matched controls. In the other study, we compared attendance at a
      postshortage Haemophilus influenzae B (Hib) immunization recall session between
      parents who received text message and paper-mailed reminders (n = 87) and those
      who only received paper-mailed reminders (n = 87). RESULTS: Significantly more
      adolescents with intervention parents received either or both MCV4 and Tdap at
      weeks 4 (15.4% vs 4.2%; P < .001), 12 (26.7% vs 13.9%; P < .005), and 24 (36.4%
      vs 18.1%; P < .001). Significantly more parents who received both Hib reminders
      attended a recall session compared with parents who only received a mailed
      reminder (21.8% vs 9.2%; P < .05). After controlling for age, gender,
      race/ethnicity, insurance status, and language, text messaging was still
      significantly associated with both studies' outcomes. CONCLUSIONS: Text messaging
      for reminder-recalls improved immunization coverage in a low-income, urban
      population.

PMID- 22390458
TI  - Program, policy, and price interventions for tobacco control: quantifying the
      return on investment of a state tobacco control program.
AB  - OBJECTIVES: We examined health effects associated with 3 tobacco control
      interventions in Washington State: a comprehensive state program, a state policy
      banning smoking in public places, and price increases. METHODS: We used linear
      regression models to predict changes in smoking prevalence and specific tobacco
      related health conditions associated with the interventions. We estimated dollars
      saved over 10 years (2000-2009) by the value of hospitalizations prevented,
      discounting for national trends. RESULTS: Smoking declines in the state exceeded
      declines in the nation. Of the interventions, the state program had the most
      consistent and largest effect on trends for heart disease, cerebrovascular
      disease, respiratory disease, and cancer. Over 10 years, implementation of the
      program was associated with prevention of nearly 36,000 hospitalizations, at a
      value of about $1.5 billion. The return on investment for the state program was
      more than $5 to $1. CONCLUSIONS: The combined program, policy, and price
      interventions resulted in reductions in smoking and related health effects, while
      saving money. Public health and other leaders should continue to invest in
      tobacco control, including comprehensive programs.

PMID- 22390459
TI  - In the wake of Guatemala: the case for voluntary compensation and remediation.
AB  - Recently unearthed records reveal that between 1946 and 1948, researchers with
      the US Public Health Service engaged in nonconsensual inoculation of vulnerable
      Guatemalan populations with syphilis, gonorrhea, or chancroid.  The US government
      has issued formal public apologies to the Guatemalan government and its people,
      and the Presidential Commission for the Study of Bioethical Issues has been
      tasked with reviewing the historical record and the adequacy of protection of
      human research participants.  We argue that the US response is insufficient and
      call for a restitution program directed at the aggrieved parties. We review the
      lessons of two earlier analogous cases and propose guiding principles upon which
      such a restitution program could be crafted with the Guatemalan people in mind.

PMID- 22390461
TI  - Influence of different mesh filter module configurations on effluent quality and
      long-term filtration performance.
AB  - Recently, a new type of wastewater treatment system became the focus of
      scientific research: the mesh filter activated sludge system. It is a
      modification of the membrane bioreactor (MBR), in which a membrane filtration
      process serves for sludge separation. The main difference is that a mesh filter
      is used instead of the membrane. The effluent is not of the same excellent
      quality as with membrane bioreactors due to the much lager pore sizes of the
      mesh. Nevertheless, it still resembles the quality of currently used standard
      treatment system, the activated sludge process. The new process shows high future
      potential as an alternative where a small footprint of these plants is required
      (3 times lower footprint than conventional activated sludge systems because of
      neglecting the secondary clarifier and reducing the biological stage). However,
      so far only limited information on this innovative process is available. In this
      study, the effect of different pore sizes and different mesh module
      configurations on the effluent quality was investigated varying the parameters
      cross-flow velocity (CFV) and flux rate. Furthermore the long-term filtration
      performance was studied in a pilot reactor system and results were compared to
      the full-scale conventional activated sludge process established at the same
      site. The results demonstrate that the configuration of the filter module has
      little impact on effluent quality and is only of importance with regard to
      engineering aspects. Most important for a successful operation are the
      hydrodynamic conditions within the filter module. The statement "the higher the
      pore size the higher the effluent turbidity" was verified. Excellent effluent
      quality with suspended solids between 5 and 15 mg L(-1) and high biological
      elimination rates (chemical oxygen demand (COD) 90-95%, biological oxygen demand
      (BOD5) 94-98%, total nitrogen (TN) 70-80%, and ammonium nitrogen (NH(4)-N) 95
      99%) were achieved and also compared to those of conventional activated sludge
      systems. Regarding the air requirement for module aeration, which is the main
      cost factor in MBR technology, an astonishing optimization could be achieved.
      During the long-term filtration experiments only 4 N m(3)/m(3) was necessary to
      keep a stable filtration process for more than 3 weeks (MBR 20-50 N m(3)/m(3)).

PMID- 22390460
TI  - Psychosocial factors associated with mouth and throat cancer examinations in
      rural Florida.
AB  - OBJECTIVES: We examined the knowledge and prevalence of mouth and throat cancer
      examinations in a sample drawn from rural populations in north Florida. METHODS:
      Telephone interviews were conducted across rural census tracts throughout north
      Florida in 2009 and 2010, in a survey that had been adapted for cultural
      appropriateness using cognitive interviews. The sample consisted of 2526
      respondents (1132 men and 1394 women; 1797 Whites and 729 African Americans).
      RESULTS: Awareness of mouth and throat cancer examination (46%) and lifetime
      receipt (46%) were higher than reported in statewide studies performed over the
      past 15 years. Only 19% of the respondents were aware of their examination,
      whereas an additional 27% reported having the examination when a description was
      provided, suggesting a lack of communication between many caregivers and rural
      patients. Surprisingly, anticipated racial/ethnic differences were diminished
      when adjustments were made for health literacy and several measures of
      socioeconomic status. CONCLUSIONS: These findings support the notion that health
      disparities are multifactorial and include characteristics such as low health
      literacy, lack of access to care, and poor communication between patient and
      provider.

PMID- 22390463
TI  - Upstream transcription factor 1 (USF1) polymorphisms associate with Alzheimer's
      disease-related neuropathological lesions: Tampere Autopsy Study.
AB  - The apolipoprotein E (APOE) gene associates with Alzheimer's disease (AD) and
      cholesterol levels. Upstream transcription factor 1 (USF1) regulates lipid
      metabolism genes, including APOE, and the AD Abeta-precursor protein. We
      investigated associations between 6 haplotype-tagging USF1 single-nucleotide
      polymorphisms (and haplotypes) and AD-related neuropathological lesions [senile
      plaques (SP), neurofibrillary tangles (NFT) ] in an autopsy series comprising 603
      cases (ages 0-97, mean 62 years, 215 women) that died out-of-hospital. In age-
      and APOE-adjusted analyses, the minor G-allele of rs2774276, previously linked to
      elevated cholesterol, associated with late-stage burnt out SP among women and
      early non-neuritic SP among men. The G-allele of the previously unreported
      rs10908821 showed significant risk of having SP, especially neuritic and burnt
      out SP, among women but not men. USF1 haplotype GCGCAC carriers (risk alleles of
      rs2774276 and rs10908821) associated with SP risk, especially neuritic and late
      stage burnt out SP, among women but not men. Younger CCGCAC carriers (risk allele
      of rs2774276 and protective of rs10908821) were more likely to have non-neuritic
      and diffuse SP. Conversely, USF1 CCGCAC haplotype carriers had lower NFT
      prevalence among 65+ year-olds. These results suggest USF1 has an independent but
      gender- and age-associated effect on AD-related brain lesion development.

PMID- 22390462
TI  - Changes in LH pulsatility profiles in dairy heifers during exposure to oestrous
      urine and vaginal mucus.
AB  - Difficulty in observing oestrus is a problem for many dairy farmers performing
      AI. Finding ways to synchronize oestrous cycles or strengthen display of oestrus
      without hormonal treatments would be of great interest because many consumers
      object to the use of exogenous hormones on healthy animals. Modification of
      reproductive cycles through chemical communication has been reported in several
      species including cattle. LH is an important regulator of the follicular phase
      and could possibly be subject to pheromonal influence. This study focuses on the
      effect of volatile compounds from oestrous substances on LH pulsatility preceding
      the preovulatory LH surge in cattle. Four heifers of the Swedish Red breed were
      kept individually in isolation. Exposure to water during the control cycle (CC),
      and bovine oestrous urine and vaginal mucus during the treated cycle (TC),
      started simultaneously with induction of oestrus. Blood sampling at 15-min
      intervals started 37 h after administration of PGF(2alpha) and continued for 8 h.
      Monitoring of reproductive hormones, visual oestrus detection and
      ultrasonographic examination of the ovaries continued until ovulation had
      occurred. The mean concentration of LH at pulse nadir was significantly higher
      during TC (2.04 +/- 0.18 ng/ml) than during CC (1.79 +/- 0.16 ng/ml), and peak
      amplitude was significantly higher during CC (Delta1.03 +/- 0.09) than during TC
      (Delta0.87 +/- 0.09). No other parameters differed significantly between the two
      cycles. We conclude that the difference in LH pulsatility pattern may be an
      effect of exposing heifers to oestrous vaginal mucus and/or urine and that the
      mechanism behind this needs further investigation.

PMID- 22390464
TI  - Body-part-specific representations of semantic noun categories.
AB  - Word meaning processing in the brain involves ventrolateral temporal cortex, but
      a semantic contribution of the dorsal stream, especially frontocentral
      sensorimotor areas, has been controversial. We here examine brain activation
      during passive reading of object-related nouns from different semantic
      categories, notably animal, food, and tool words, matched for a range of
      psycholinguistic features. Results show ventral stream activation in temporal
      cortex along with category-specific activation patterns in both ventral and
      dorsal streams, including sensorimotor systems and adjacent pFC. Precentral
      activation reflected action-related semantic features of the word categories.
      Cortical regions implicated in mouth and face movements were sparked by food
      words, and hand area activation was seen for tool words, consistent with the
      actions implicated by the objects the words are used to speak about. Furthermore,
      tool words specifically activated the right cerebellum, and food words activated
      the left orbito-frontal and fusiform areas. We discuss our results in the context
      of category-specific semantic deficits in the processing of words and concepts,
      along with previous neuroimaging research, and conclude that specific dorsal and
      ventral areas in frontocentral and temporal cortex index visual and affective
      emotional semantic attributes of object-related nouns and action-related
      affordances of their referent objects.

PMID- 22390466
TI  - Local field potential activity associated with temporal expectations in the
      macaque lateral intraparietal area.
AB  - Oscillatory brain activity is attracting increasing interest in cognitive
      neuroscience. Numerous EEG (magnetoencephalography) and local field potential
      (LFP) measurements have related cognitive functions to different types of brain
      oscillations, but the functional significance of these rhythms remains poorly
      understood. Despite its proven value, LFP activity has not been extensively
      tested in the macaque lateral intraparietal area (LIP), which has been implicated
      in a wide variety of cognitive control processes. We recorded action potentials
      and LFPs in area LIP during delayed eye movement tasks and during a passive
      fixation task, in which the time schedule was fixed so that temporal expectations
      about task-relevant cues could be formed. LFP responses in the gamma band
      discriminated reliably between saccade targets and distractors inside the
      receptive field (RF). Alpha and beta responses were much less strongly affected
      by the presence of a saccade target, however, but rose sharply in the waiting
      period before the go signal. Surprisingly, conditions without visual stimulation
      of the LIP-RF-evoked robust LFP responses in every frequency band--most
      prominently in those below 50 Hz--precisely time-locked to the expected time of
      stimulus onset in the RF. These results indicate that in area LIP, oscillations
      in the LFP, which reflect synaptic input and local network activity, are tightly
      coupled to the temporal expectation of task-relevant cues.

PMID- 22390465
TI  - Age-related neural reorganization during spoken word recognition: the interaction
      of form and meaning.
AB  - Research on language and aging typically shows that language comprehension is
      preserved across the life span. Recent neuroimaging results suggest that this
      good performance is underpinned by age-related neural reorganization [e.g.,
      Tyler, L. K., Shafto, M. A., Randall, B., Wright, P., Marslen-Wilson, W. D., &
      Stamatakis, E. A. Preserving syntactic processing across the adult life span: The
      modulation of the frontotemporal language system in the context of age-related
      atrophy. Cerebral Cortex, 20, 352-364, 2010]. The current study examines how age
      related reorganization affects the balance between component linguistic processes
      by manipulating semantic and phonological factors during spoken word recognition
      in younger and older adults. Participants in an fMRI study performed an auditory
      lexical decision task where words varied in their phonological and semantic
      properties as measured by degree of phonological competition and imageability.
      Older adults had a preserved lexicality effect, but compared with younger people,
      their behavioral sensitivity to phonological competition was reduced, as was
      competition-related activity in left inferior frontal gyrus. This was accompanied
      by increases in behavioral sensitivity to imageability and imageability-related
      activity in left middle temporal gyrus. These results support previous findings
      that neural compensation underpins preserved comprehension in aging and
      demonstrate that neural reorganization can affect the balance between semantic
      and phonological processing.

PMID- 22390467
TI  - The path to memory is guided by strategy: distinct networks are engaged in
      associative encoding under visual and verbal strategy and influence memory
      performance in healthy and impaired individuals.
AB  - Given the diversity of stimuli encountered in daily life, a variety of strategies
      must be used for learning new information. Relating and encoding visual and
      verbal stimuli into memory has been probed using various tasks and stimulus
      types. Engagement of specific subsequent memory and cortical processing regions
      depends on the stimulus modality of studied material; however, it remains unclear
      whether different encoding strategies similarly influence regional activity when
      stimulus type is held constant. In this study, participants encoded object pairs
      using a visual or verbal associative strategy during fMRI, and subsequent memory
      was assessed for pairs encoded under each strategy. Each strategy elicited
      distinct regional processing and subsequent memory effects: middle/superior
      frontal, lateral parietal, and lateral occipital for visually associated pairs
      and inferior frontal, medial frontal, and medial occipital for verbally
      associated pairs. This regional selectivity mimics the effects of stimulus
      modality, suggesting that cortical involvement in associative encoding is driven
      by strategy and not simply by stimulus type. The clinical relevance of these
      findings, probed in a patient with a recent aphasic stroke, suggest that training
      with strategies utilizing unaffected cortical regions might improve memory
      ability in patients with brain damage.

PMID- 22390469
TI  - Isotretinoin is safe and efficacious in Asians with acne vulgaris.
AB  - BACKGROUND: Oral isotretinoin is effective for acne vulgaris but concerns remain
      regarding its adverse effects. OBJECTIVES: This study aims to evaluate the safety
      and efficacy of isotretinoin for acne vulgaris in Asian patients. METHODS: We
      conducted a 4-year retrospective study on all patients with acne vulgaris treated
      with isotretinoin, between January 2005 and December 2008 at the National Skin
      Centre in Singapore. Medical records were reviewed for information on patient
      demographics, acne severity, isotretinoin dose, duration, adverse effects and
      outcome. RESULTS: There were 2,255 patients, with a mean age of 22.5 years,
      male:female ratio of 2.5:1 and 82.3% being Chinese. The mean starting dose of
      isotretinoin was 0.4 mg/kg and on average, patients received 7.8 months of
      treatment at a mean dose of 0.5 mg/kg. Mean total cumulative dose was 95.6 mg/kg.
      Vast majority (93.9%) achieved complete remission or substantial improvement.
      Thirty-eight (2.2%) and 24 patients (2.7%) developed elevated serum levels of
      alanine and aspartate aminotransferases subsequent to treatment. There were 194
      (12.1%) and 80 (4.8%) patients who developed hyperlipidaemia and
      hypertriglyceridaemia respectively. Isotretinoin was generally well-tolerated,
      with 6.4% (n = 145) discontinuing due to side-effects. CONCLUSIONS: This study
      reaffirms the overall safety and efficacy of oral isotretinoin in Asian patients
      with acne vulgaris.

PMID- 22390470
TI  - Electrochemically induced chemically reversible proton-coupled electron transfer
      reactions of riboflavin (vitamin B2).
AB  - The electrochemical behavior of the naturally occurring vitamin B(2), riboflavin
      (Fl(ox)), was examined in detail in dimethyl sulfoxide solutions using variable
      scan rate cyclic voltammetry (nu = 0.1 - 20 V s(-1)) and has been found to
      undergo a series of proton-coupled electron transfer reactions. At a scan rate of
      0.1 V s(-1), riboflavin is initially reduced by one electron to form the radical
      anion (Fl(rad)(*-)) at E(0)(f) = -1.22 V versus Fc/Fc(+) (E(0)(f) = formal
      reduction potential and Fc = ferrocene). Fl(rad)(*-) undergoes a homogeneous
      proton transfer reaction with the starting material (Fl(ox)) to produce
      Fl(rad)H(*) and Fl(ox)(-), which are both able to undergo further reduction at
      the electrode surface to form Fl(red)H(-) (E(0)(f) = -1.05 V vs Fc/Fc(+)) and
      Fl(rad)(*2-) (E(0)(f) = -1.62 V vs Fc/Fc(+)), respectively. At faster
      voltammetric scan rates, the homogeneous reaction between Fl(rad)(*-) and Fl(ox)
      begins to be outrun, which leads to the detection of a voltammetric peak at more
      negative potentials associated with the one-electron reduction of Fl(rad)(*-) to
      form Fl(red)(2-) (E(0)(f) = -1.98 V vs Fc/Fc(+)). The variable scan rate
      voltammetric data were modeled quantitatively using digital simulation techniques
      based on an interconnecting "scheme of squares" mechanism, which enabled the four
      formal potentials as well as the equilibrium and rate constants associated with
      four homogeneous reactions to be determined. Extended time-scale controlled
      potential electrolysis (t > hours) and spectroscopic (EPR and in situ UV-vis)
      experiments confirmed that the chemical reactions were completely chemically
      reversible.

PMID- 22390473
TI  - Exploring exciton relaxation and multiexciton generation in PbSe nanocrystals
      using hyperspectral near-IR probing.
AB  - Hyperspectral femtosecond transient absorption spectroscopy is employed to record
      exciton relaxation and recombination in colloidal lead selenide (PbSe)
      nanocrystals in unprecedented detail. Results obtained with different pump
      wavelengths and fluences are scrutinized with regard to three issues: (1) early
      subpicosecond spectral features due to "hot" excitons are analyzed in terms of
      suggested underlying mechanisms; (2) global kinetic analysis facilitates
      separation of the transient difference spectra into single, double, and triple
      exciton state contributions, from which individual band assignments can be
      tested; and (3) the transient spectra are screened for signatures of multiexciton
      generation (MEG) by comparing experiments with excitation pulses both below and
      well above the theoretical threshold for multiplication. For the latter, a
      recently devised ultrafast pump-probe spectroscopic approach is employed. Scaling
      sample concentrations and pump pulse intensities inversely with the extinction
      coefficient at each excitation wavelength overcomes ambiguities due to direct
      multiphoton excitation, uncertainties of absolute absorption cross sections, and
      low signal levels. As observed in a recent application of this method to InAs
      core/shell/shell nanodots, no sign of MEG was detected in this sample up to
      photon energy 3.7 times the band gap. Accordingly, numerous reports of efficient
      MEG in other samples of PbSe suggest that the efficiency of this process varies
      from sample to sample and depends on factors yet to be determined.

PMID- 22390472
TI  - NT-proBNP, echocardiographic abnormalities and subclinical coronary artery
      disease in high risk type 2 diabetic patients.
AB  - BACKGROUND: Intensive multifactorial treatment aimed at prevention of
      cardiovascular (CV) disease may reduce left ventricular (LV) echocardiographic
      abnormalities in diabetic subjects. Plasma N-terminal (NT)-proBNP predicts CV
      mortality in diabetic patients but the association between P-NT-proBNP and the
      putative residual abnormalities in such patients are not well described. This
      study examined echocardiographic measurements of LV hypertrophy, atrial
      dilatation and LV dysfunction and their relation to P-NT-proBNP levels or
      subclinical coronary artery disease (CAD) in type 2 diabetic patients with
      microalbuminuria receiving intensive multifactorial treatment. METHODS:
      Echocardiography including tissue Doppler imaging and P-NT-proBNP measurements
      were performed in 200 patients without prior CAD. Patients with P-NT-proBNP >
      45.2 ng/L and/or coronary calcium score >= 400 were stratified as high risk
      patients for CAD(n = 133) and examined for significant CAD by myocardial
      perfusion imaging and/or CT-angiography and/or coronary angiography. RESULTS: LV
      mass index was 41.2 +/- 10.9 g/m2.7 and 48 (24%) patients had LV hypertrophy. LA
      and RA dilatation were found in 54(27%) and 45(23%) patients, respectively, and
      LV diastolic dysfunction was found in 109(55%) patients. Patients with increased
      P-NT-proBNP levels did not have more major echocardiographic abnormalities. In
      70(53%) of 133 high risk patients significant CAD was demonstrated and patients
      with LV hypertrophy had increased risk of significant CAD(adjusted odd ratio[CI]
      was 4.53[1.14-18.06]). CONCLUSION: Among asymptomatic type 2 diabetic patients
      with microalbuminuria that received intensive multifactorial treatment, P-NT
      proBNP levels is not associated with echocardiographic abnormalities. LV
      diastolic dysfunction was frequently observed, whereas LV hypertrophy was less
      frequent but associated with significant CAD.

PMID- 22390474
TI  - Pseudomonas aeruginosa population structure revisited under environmental focus:
      impact of water quality and phage pressure.
AB  - Pseudomonas aeruginosa attracts research attention as a common opportunistic
      nosocomial pathogen causing severe health problems in humans. Nevertheless, its
      primary habitat is the natural environment. Here, we relate the genetic diversity
      of 381 environmental isolates from rivers in northern Germany to ecological
      factors such as river system, season of sampling and different levels of water
      quality. From representatives of 99 environmental clones, also in comparison with
      91 clinical isolates, we determined motility phenotypes, virulence factors,
      biofilm formation, serotype and the resistance to seven environmental
      P.aeruginosa phages. The integration of genetic, ecological and phenotypic data
      showed (i) the presence of several extended clonal complexes (ecc) which are non
      uniformly distributed across different water qualities, and (ii) a correlation of
      the hosts' serotype composition with susceptibility towards distinct groups of
      environmental phages. For at least one ecc (eccB), we assumed the
      ecophysiological differences on environmental water adaptation and phage
      resistance to be so distinct as to reinforce an environmentally driven cladogenic
      split from the remainder of P.aeruginosa. In summary, we conclude that the
      majority of the microevolutionary population dynamics of P.aeruginosa were shaped
      by the natural environment and not by the clinical habitat.

PMID- 22390475
TI  - Subject-based reference values: biological variation, individuality, and
      reference change values.
AB  - Subject-based reference values have been largely overlooked in veterinary
      medicine. These values represent longitudinal data rather than the cross
      sectional data represented by standard population-based reference values. As such
      they provide information about biological and analytical variation. Inherent
      random variation of analytes around a homeostatic set point is referred to as
      biological variation; data on biological variation are underutilized in
      veterinary medicine and have multiple applications that include setting
      analytical goals, predicting the utility of population-based reference intervals
      (RIs), assessing the value of partitioning reference values, and evaluating the
      significance of changes in serial results. To generate these data, relatively few
      individuals are sampled for a short period of time. Given the difficulty of
      obtaining specimens from large number of healthy individuals to establish a cross
      sectional RI for many veterinary species, especially exotic species, use of
      subject-based RIs is a practical alternative approach for the veterinary
      diagnostician. Furthermore, for the majority of biochemical analytes and even
      many hemostatic variables, population-based reference values are less sensitive
      than subject-based reference values for detecting pathologic changes in an
      individual. The focus of this review is the clinical usefulness of subject-based
      reference values and diagnostic implications for their use. Implementation of the
      concepts of biological variation, individuality, and reference change value (RCV)
      may allow large diagnostic laboratories to offer more sensitive reference values
      to assess health and detect disease.

PMID- 22390476
TI  - Size and emotion averaging: costs of dividing attention after all.
AB  - Perceptual averaging is a process by which sets of similar items are represented
      by summary statistics such as their average size, luminance, or orientation.
      Researchers have argued that this process is automatic, able to be carried out
      without interference from concurrent processing. Here, we challenge this
      conclusion and demonstrate a reliable cost of computing the mean size of circles
      distinguished by colour (Experiments 1 and 2) and the mean emotionality of faces
      distinguished by sex (Experiment 3). We also test the viability of two strategies
      that could have allowed observers to guess the correct response without computing
      the average size or emotionality of both sets concurrently. We conclude that
      although two means can be computed concurrently, doing so incurs a cost of
      dividing attention.

PMID- 22390477
TI  - [The influence of semantic richness on the visual recognition of emotional
      words].
AB  - The aim of this study was to expand our knowledge of the influence of emotional
      valence on visual word recognition by answering two questions. The first was to
      examine whether the emotional valence effect is sensitive to different types of
      task requirements, and the second was to examine whether words polysemy can
      modulate the effect of emotional valence. For this purpose, we manipulated
      orthogonally emotional valence (negative, positive and neutral words) and
      polysemy (polysemous vs. non polysemous words) in two versions of the lexical
      decision task (one with legal nonwords and one with illegal nonwords). Results
      showed an effect of task: emotional valence and polysemy influenced lexical
      decision latencies only in the legal version of the lexical-decision task.
      Furthermore, results showed that the effect of polysemy was dependant on
      emotional valence. We observed a facilitation of polysemy for neutral words but
      not for emotional ones. Finally this experiment also showed that polysemy
      modulates the emotional valence effect. The facilitation observed for non
      polysemous emotional words compared to non polysemous neutral words disappeared
      for polysemous words. These findings fit with other studies showing facilitation
      for emotional word recognition and allow conclusions concerning the role of
      semantics on emotional word recognition.

PMID- 22390478
TI  - Response of glutathione S-transferase Pi (GSTP1) to neoadjuvant therapy in rectal
      adenocarcinoma.
AB  - AIM: The response of rectal adenocarcinoma to neoadjuvant therapy is variable.
      Accurate prediction of response would enable selective administration of therapy.
      The enzyme glutathione S-transferase Pi (GSTP1) has been shown to influence
      response to therapy in some solid tumours. Few data are available for rectal
      cancer. METHOD: The GSTP1 levels in rectal adenocarcinoma and adjacent normal
      mucosa were quantified before and after exposure to neoadjuvant therapy. Venous
      blood samples and biopsies of normal rectal mucosa and tumour were prospectively
      obtained from patients with primary rectal cancer. Patients were stratified by
      exposure to neoadjuvant therapy or surgery alone. GSTP1 was quantitatively
      measured using an enzyme-linked immunosorbent assay. RESULTS: Ninety-two patients
      (54 men; median age 68 years) were recruited. The median GSTP1 level was
      significantly higher in rectal adenocarcinoma than in matched normal mucosa [6.59
      MUg/mg vs 4.57 MUg/mg; P < 0.001]. The median tumour GSTP1 level was
      significantly lower in the therapy group compared with unmatched samples from the
      no-therapy group [4.47 MUg/mg vs 7.76 MUg/mg; P < 0.001]. CONCLUSION: The GSTP1
      level is increased in rectal adenocarcinoma compared with adjacent normal mucosa.
      It decreases following neoadjuvant therapy. Future studies correlating pre
      therapy GSTP1 levels with pathological response would be of interest.

PMID- 22390480
TI  - Production of zebrafish offspring from cultured spermatogonial stem cells.
AB  - Germ-line stem cells have the potential to be a very powerful tool for modifying
      the genetic information of individual animals. As a first step to use
      spermatogonial stem cells (SSCs) to enable genetic modification, we here describe
      effective long-term culture conditions for propagating zebrafish SSCs and for the
      production of offspring from these cultured SSCs after their differentiation into
      sperm in transplanted testicular cell aggregates. Dissociated testicular cells
      were cultured in specific medium with some modified supplements, including
      several mammalian growth factors. The spermatogonia actively proliferated and
      retained the expression of exogenous green fluorescent protein under the control
      of vas and sox17 promoters and also of promyelocytic leukemia zinc finger (Plzf),
      a marker of undifferentiated spermatogonia, after 1 month in culture. This is a
      longer period than the entire natural spermatogenic cycle (from SSCs to sperm).
      The use of subcutaneously grafted aggregates of these cultured spermatogonia and
      freshly dissociated testicular cells showed that these SSCs could undergo self
      renewal and differentiation into sperm. Artificial insemination of these grafted
      aggregates successfully produced offspring. This culture method will facilitate
      the identification of new factors for the maintenance of SSCs and enable the
      future enrichment of genetically modified SSCs that will produce offspring in
      zebrafish.

PMID- 22390479
TI  - The role of immunosuppression of mesenchymal stem cells in tissue repair and
      tumor growth.
AB  - Mesenchymal stem cells (MSCs) have acquired great interests for their potential
      use in the clinical therapy of many diseases because of their functions including
      multiple lineage differentiation, low immunogenicity and immunosuppression. Many
      studies suggest that MSCs are strongly immunosuppressive in vitro and in vivo.
      MSCs exert a profound inhibitory effect on the proliferation of T cells, B cells,
      dendritic cells and natural killer cells. In addition, several soluble factors
      have been reported to involved in the immunosuppressive effects by MSCs such as
      TGF-beta, HGF, PGE2, IDO and iNOS. These results suggest that MSCs can be used in
      the therapy of immune disorder diseases, prevention of organ transplantation
      rejection and tissue injury. In recent study, we demonstrated that MSCs in tumor
      inflammatory microenvironment might be elicited of immunosuppressive function.
      Thus, the application of MSCs in cancer therapy might have negative effect by
      helping tumor cells escaping from the immune surveillance.

PMID- 22390481
TI  - Are the effects of alcohol on the CNS influenced by Toll-like receptor signaling?

PMID- 22390482
TI  - PKCtheta: a new target for selective immunosuppression.

PMID- 22390484
TI  - Twelve years' experience with etanercept in the treatment of rheumatoid
      arthritis: how it has changed clinical practice.
AB  - Etanercept is approved for the treatment of patients with moderate-to-severe
      active rheumatoid arthritis (RA), polyarticular juvenile RA, ankylosing
      spondylitis, psoriatic arthritis and plaque psoriasis. Randomized clinical trials
      have shown that it improves the signs and symptoms of early and long-standing RA
      and other inflammatory arthritides, prevents radiographic progression and
      improves the patients' health-related quality of life. It is more effective when
      combined with methotrexate than alone. It is generally well tolerated, and seems
      to be relatively safe in the short term, as confirmed by clinical trials, long
      term observational studies and postmarketing surveillance over 12 years' use in
      clinical practice. It slightly increases the risk of serious infections. The
      incidence of malignancies during clinical trials and postmarketing surveillance
      is no different from that expected in the general population, except for the
      greater frequency of lymphoma. However, this is closely related to current RA
      activity and therefore suggests that it is not directly related to the drug. This
      article considers the published data in terms of clinical practice and changes in
      the progression of RA.

PMID- 22390485
TI  - Immunodeficiency: updating the personalized medicine approach to diagnostics and
      therapeutics.
AB  - The 2011 UK Primary Immunodeficiency Network Forum was held in the Liverpool
      Arena and Conference Centre. Over 200 healthcare scientists, nurses and doctors
      were in attendance to discuss a range of issues relating to primary immune
      deficiencies. This year the biennial forum saw both national and international
      speakers and a broad representation of posters and oral abstracts from across the
      interest groups. This article summarizes the keynote lectures and output from 2
      days including more than 70 poster presentations and 25 oral presentations.

PMID- 22390486
TI  - LRRK2 as a negative regulator of NFAT: implications for the pathogenesis of
      inflammatory bowel disease.
AB  - Inflammatory bowel disease encompasses two chronic, complex relapsing diseases
      believed to be caused by an excessive and poorly controlled immune response to
      the intestinal microbiota. The advent of genome-wide association scans has
      allowed for rapid identification of multiple susceptibility genes for Crohn's
      disease and ulcerative colitis. A locus containing LRRK2 and MUC19 is a confirmed
      Crohn's disease susceptibility locus. This genetic association precipitates an
      important functional study in which Liu et al. demonstrate that: LRRK2 acts as a
      negative regulator of NFAT in an NRON-dependent manner; LRRK2-deficient mice
      exhibit increased susceptibility to the development of dextran sodium sulfate
      colitis, which is enhanced by NFAT translocation to the nucleus; and patients
      exhibiting the risk LRRK2 allele have lower LRRK2 protein levels and exhibit less
      inhibition of NFAT. These data support the concept that defects within innate
      immunity trigger a robust adaptive immune response, which results in the
      production of proinflammatory cytokines and the development of chronic
      inflammation of the gastrointestinal mucosa.

PMID- 22390487
TI  - Abatacept in the long-term treatment of rheumatoid arthritis.
AB  - The last decade has been an era of exciting and innovative therapeutic targets in
      the treatment of moderate-to-severe rheumatoid arthritis. One such treatment that
      acts by disrupting T-cell activation is abatacept, which is currently used in
      patients who have had an inadequate clinical response to traditional disease
      modifying drugs or anti-TNF therapies. As newer therapies emerge, issues that
      need addressing include: long-term drug tolerance, adverse events, sustained
      clinical response, prevention of progression in structural damage and retention
      rates. In this article we discuss a recently published paper by Kremer et al.
      that reported 3-year data on safety, efficacy and radiographic progression in
      patients enrolled in a clinical trial of abatacept, as well as the advantages and
      limitations of long-term extension studies.

PMID- 22390488
TI  - Stress, the neuroendocrine system and mast cells: current understanding of their
      role in psoriasis.
AB  - Psychological stress can activate the hypothalamic-pituitary-adrenal axis and
      sensory nerves in the brain and skin, resulting in the release of neuroendocrine
      and neural mediators such as, corticotropin-releasing hormone, neuropeptides,
      neurotrophins and alpha-melanocyte-stimulating hormone. These factors can
      activate mast cells to release proinflammatory mediators and some of them, for
      example, histamine, tryptase and nerve growth factor, can stimulate sensory C
      fibers. Since corticotropin-releasing hormone, sensory nerves and mast cell
      numbers are increased in the psoriatic lesion, a feedforward loop can exist
      potentiating the inflammation. Studies in rats and mice have shown that mast
      cells are activated during standardized stress through corticotropin-releasing
      hormone and sensory nerves. Therefore, the role of stress, the neuroendocrine
      system and mast cells in psoriasis is discussed in this article.

PMID- 22390489
TI  - FcgammaRIIB: a modulator of cell activation and humoral tolerance.
AB  - An immune response needs to be tightly regulated to prevent excessive
      inflammation, which may result in the destruction of healthy tissues. At the
      molecular level, the strength of an immune response is determined by the
      integration of a multitude of positive and negative signals. This review will
      focus on IgG-dependent immune responses and discuss how the inhibitory receptor
      FcgammaRIIB may be involved in regulating both the afferent and efferent phases
      of such a response. Furthermore, we will discuss recent evidence suggesting that
      FcgammaRIIB may have important functions beyond the negative regulation of
      signals transduced by the B-cell receptor or activating FcgammaRs and could be
      responsible for the activity of agonistic antibodies in vivo.

PMID- 22390490
TI  - Reduced-intensity conditioning for allogeneic stem cell transplant in primary
      immune deficiencies.
AB  - Conventional myeloablative conditioning regimens prior to hematopoietic cell
      transplantation (HCT) are associated with significant transplant-related
      morbidity and mortality in children affected by primary immunodeficiency
      disorders. Reduced-intensity conditioning regimens have been extensively used
      without severe acute toxicity in patients with pre-HCT comorbidities, with the
      additional advantage of reducing or avoiding long-term sequelae such as
      infertility and growth retardation. Compared with myeloablative HCT, reduced
      intensity conditioning regimens are associated with an increased incidence of
      mixed donor chimerism and graft rejection. While mixed donor engraftment is
      likely to correct the phenotypic expression of most children with primary
      immunodeficiency disorders, the use of donor lymphocyte infusion to increase
      donor chimerism or second HCT procedures may be required in some cases. Here we
      discuss the most recent data on the use of different reduced-intensity
      conditioning protocols in children with primary immunodeficiency disorders,
      highlighting significant clinical lessons and areas that need additional study.

PMID- 22390493
TI  - Synergism of science and social justice.

PMID- 22390492
TI  - Autoimmunity in chronic obstructive pulmonary disease: clinical and experimental
      evidence.
AB  - Over the past few decades, neutrophils and macrophages had co-occupied center
      stage as the critical innate immune cells underlying the pathobiology of
      cigarette smoke-induced chronic obstructive pulmonary disease and lung
      parenchymal destruction (i.e., emphysema). While chronic exposure to smoke
      facilitates the recruitment of innate immune cells into the lung, a clear role
      for adaptive immunity in emphysema has emerged. Evidence from human studies
      specifically point to a role for recruitment and activation of pathogenic
      lymphocytes and lung antigen-presenting cells in emphysema; similarly, animal
      models have confirmed a significant role for autoimumnity in progressive smoke
      induced emphysema. Increased numbers of activated antigen-presenting cells, Th1
      and Th17 cells, have been associated with smoke-induced lung inflammation and
      production of the canonical cytokines of these cells, IFN-gamma and IL-17,
      correlates with disease severity. These exciting new breakthroughs could open new
      avenues for developing effective new therapies for smoke-induced emphysema.

PMID- 22390495
TI  - Human papillomavirus vaccine inaccuracies.

PMID- 22390491
TI  - Autoimmune heart disease: role of sex hormones and autoantibodies in disease
      pathogenesis.
AB  - Cardiovascular disease (CVD) and autoimmune diseases (ADs) are the first and
      third highest causes of death in the USA, respectively. Men have an increased
      incidence of the majority of CVDs, including atherosclerosis, myocarditis,
      dilated cardiomyopathy and heart failure. By contrast, nearly 80% of all ADs
      occur in women. However, in one category of ADs, rheumatic diseases, CVD is the
      main cause of death. Factors that link rheumatic ADs to CVD are inflammation and
      the presence of autoantibodies. In this review we will examine recent findings
      regarding sex differences in the immunopathogenesis of CVD and ADs, explore
      possible reasons for the increased occurrence of CVD within rheumatic ADs and
      discuss whether autoantibodies, including rheumatoid factor, could be involved in
      disease pathogenesis.

PMID- 22390497
TI  - Dental therapists are a positive innovation.

PMID- 22390499
TI  - Aging and health in America: a tale from two boomers.

PMID- 22390500
TI  - Aging in the United States: opportunities and challenges for public health.

PMID- 22390501
TI  - Current considerations about the elderly and firearms.
AB  - In the United States, more than 17 million people aged 65 years or older own a
      firearm. They have the highest rate of suicide by a firearm, and recent data
      suggest that a disproportionate number apply to carry a concealed weapon. At
      least one new handgun has been designed and marketed for older people.  Memory,
      thinking, and judgment as well as physical and behavioral competence issues
      related to an elderly person's safe operation of a motor vehicle apply to
      firearms, too. Gun availability can pose a particular risk to those with dementia
      and to their caretakers.  The elderly constitute a substantial and rapidly
      growing population and market segment for whom the public health implications of
      firearm production, promotion, access, ownership, and use merit consideration.

PMID- 22390502
TI  - Health behavior change: can genomics improve behavioral adherence?
AB  - The National Human Genome Research Institute recommends pursuing "genomic
      information to improve behavior change interventions" as part of its strategic
      vision for genomics. The limited effectiveness of current behavior change
      strategies may be explained, in part, by their insensitivity to individual
      variation in adherence responses.  The first step in evaluating whether genomics
      can inform customization of behavioral recommendations is evidence reviews to
      identify adherence macrophenotypes common across behaviors and individuals that
      have genetic underpinnings. Conceptual models of how biological, psychological,
      and environmental factors influence adherence also are needed.  Researchers could
      routinely collect biospecimens and standardized adherence measurements of
      intervention participants to enable understanding of genetic and environmental
      influences on adherence, to guide intervention customization and prospective
      comparative effectiveness studies.

PMID- 22390503
TI  - Knowledgeable Neighbors: a mobile clinic model for disease prevention and
      screening in underserved communities.
AB  - The Family Van mobile health clinic uses a "Knowledgeable Neighbor" model to
      deliver cost-effective screening and prevention activities in underserved
      neighborhoods in Boston, MA. We have described the Knowledgeable Neighbor model
      and used operational data collected from 2006 to 2009 to evaluate the service.
      The Family Van successfully reached mainly minority low-income men and women. Of
      the clients screened, 60% had previously undetected elevated blood pressure, 14%
      had previously undetected elevated blood glucose, and 38% had previously
      undetected elevated total cholesterol. This represents an important model for
      reaching underserved communities to deliver proven cost-effective prevention
      activities, both to help control health care costs and to reduce health
      disparities.

PMID- 22390504
TI  - Burden of oral disease among older adults and implications for public health
      priorities.
AB  - Dental disease is largely preventable. Many older adults, however, experience
      poor oral health.  National data for older adults show racial/ethnic and income
      disparities in untreated dental disease and oral health-related quality of life.
      Persons reporting poor versus good health also report lower oral health-related
      quality of life.  On the basis of these findings, suggested public health
      priorities include better integrating oral health into medical care, implementing
      community programs to promote healthy behaviors and improve access to preventive
      services, developing a comprehensive strategy to address the oral health needs of
      the homebound and long-term-care residents, and assessing the feasibility of
      ensuring a safety net that covers preventive and basic restorative services to
      eliminate pain and infection.

PMID- 22390505
TI  - Clinical preventive services for older adults: the interface between personal
      health care and public health services.
AB  - Healthy aging must become a priority objective for both population and personal
      health services, and will require innovative prevention programming to span those
      systems. Uptake of essential clinical preventive services is currently suboptimal
      among adults, owing to a number of system- and office-based care barriers.  To
      achieve maximum health results, prevention must be integrated across community
      and clinical settings. Many preventive services are portable, deliverable in
      either clinical or community settings. Capitalizing on that flexibility can
      improve uptake and health outcomes.  Significant reductions in health
      disparities, mortality, and morbidity, along with decreases in health spending,
      are achievable through improved collaboration and synergy between population
      health and personal health systems.

PMID- 22390506
TI  - A public health approach to addressing arthritis in older adults: the most common
      cause of disability.
AB  - Arthritis is highly prevalent and is the leading cause of disability among older
      adults in the United States owing to the aging of the population and increases in
      the prevalence of risk factors (e.g., obesity). Arthritis will play a large role
      in the health-related quality of life, functional independence, and disability of
      older adults in the upcoming decades. We have emphasized the role of the public
      health system in reducing the impact of this large and growing public health
      problem, and we have presented priority public health actions.

PMID- 22390507
TI  - Strategies for managing the dual risk of sexually transmitted infections and
      unintended pregnancy among Puerto Rican and African American young adults.
AB  - Although young adults in the United States are at increased risk for sexually
      transmitted infections (STIs) and unintended pregnancy, they do not report high
      rates of dual-method use (condoms plus other contraception) for prevention. We
      used prospective qualitative data from 69 urban Puerto Rican and African American
      individuals aged 18 to 25 years to determine how they managed these risks in
      their heterosexual relationships during a 4- to 8-week period. Hormonal or long
      acting contraceptive use, condoms, and withdrawal were the most common unintended
      pregnancy prevention strategies; condoms, STI testing, and perceived fidelity
      were dominant among STI prevention strategies. We need to shift the focus from
      dual-method use toward a broader concept of dual protection to be more responsive
      to young adults' concerns, perceptions, and priorities.

PMID- 22390508
TI  - Community epidemiology of risk and adolescent substance use: practical questions
      for enhancing prevention.
AB  - To promote an effective approach to prevention, the community diagnosis model
      helps communities systematically assess and prioritize risk factors to guide the
      selection of preventive interventions. This increasingly widely used model relies
      primarily on individual-level research that links risk and protective factors to
      substance use outcomes. I discuss common assumptions in the translation of such
      research concerning the definition of risk factor elevation; the equivalence,
      independence, and stability of relations between risk factors and problem
      behaviors; and community differences in risk factors and risk factor-problem
      behavior relations. Exploring these assumptions could improve understanding of
      the relations of risk factors and substance use within and across communities and
      enhance the efficacy of the community diagnosis model. This approach can also be
      applied to other areas of public health where individual and community levels of
      risk and outcomes intersect.

PMID- 22390509
TI  - Enumeration and composition of the public health workforce: challenges and
      strategies.
AB  - The field of public health needs a comprehensive classification data system that
      provides a better assessment of the size and composition of its workforce. Such a
      data system is necessary for understanding the capacity, trend projections, and
      policy development critical to the future workforce.  Previous enumeration and
      composition studies on the public health workforce have been helpful, but the
      methodology used needs further improvements in standardization, specificity, data
      storage, and data availability. Resolving this issue should follow a consensus
      based course of action that includes public and private stakeholders at the
      national, state, and local level.  This prime issue should be addressed now,
      particularly in the current environment of comprehensive health care reform.

PMID- 22390510
TI  - Dual loyalty in prison health care.
AB  - Despite the dissemination of principles of medical ethics in prisons, formulated
      and advocated by numerous international organizations, health care professionals
      in prisons all over the world continue to infringe these principles because of
      perceived or real dual loyalty to patients and prison authorities.  Health care
      professionals and nonmedical prison staff need greater awareness of and training
      in medical ethics and prisoner human rights. All parties should accept
      integration of prison health services with public health services.  Health care
      workers in prison should act exclusively as caregivers, and medical tasks
      required by the prosecution, court, or security system should be carried out by
      medical professionals not involved in the care of prisoners.

PMID- 22390511
TI  - Informed consent and cluster-randomized trials.
AB  - We argue that cluster-randomized trials are an important methodology, essential
      to the evaluation of many public health interventions.  However, in the case of
      at least some cluster-randomized trials, it is not possible, or is incompatible
      with the aims of the study, to obtain individual informed consent. This should
      not necessarily be seen as an impediment to ethical approval, providing that
      sufficient justification is given for this omission.  We further argue that it
      should be the institutional review board's task to evaluate whether the protocol
      is sufficiently justified to proceed without consent and that this is preferable
      to any reliance on community consent or other means of proxy consent.

PMID- 22390512
TI  - Understanding barriers to and facilitators of diabetes control and prevention in
      the New York City Bangladeshi community: a mixed-methods approach.
AB  - We have reported results from the formative stage of a community health worker
      intervention designed to improve diabetes management among Bangladeshi patients
      in New York City. Trained community health workers conducted focus groups (n =
      47) and surveys (n = 169) with Bangladeshi individuals recruited from community
      locations. Results indicated that participants faced numerous barriers to care,
      had high rates of limited English proficiency, and had low levels of knowledge
      about diabetes. Most participants expressed interest in participating in a
      community health worker intervention.

PMID- 22390513
TI  - Adolescent health and harassment based on discriminatory bias.
AB  - Is harassment based on personal characteristics such as race/ethnicity, sexual
      orientation, religion, or disability more detrimental than general harassment? In
      2 large population-based studies of adolescents, more than one third of those
      harassed reported bias-based school harassment. Both studies show that bias-based
      harassment is more strongly associated with compromised health than general
      harassment. Research on harassment among youths rarely examines the underlying
      cause. Attention to bias or prejudice in harassment and bullying should be
      incorporated into programs and policies for young people.

PMID- 22390514
TI  - Health-related quality of life among older adults with and without functional
      limitations.
AB  - OBJECTIVES: We examined factors that influence health-related quality of life
      (HRQOL) among individuals aged 50 years and older with and without functional
      limitations. METHODS: We analyzed data from the 2009 Behavioral Risk Factor
      Surveillance System to assess associations among demographic characteristics,
      health care access and utilization indicators, modifiable health behaviors, and
      HRQOL characterized by recent physically and mentally unhealthy days in those
      with and those without functional limitations. We defined functional limitations
      as activity limitations owing to physical, mental, or emotional health or as the
      need for special equipment because of health. RESULTS: Age, medical care costs,
      leisure-time physical activity, and smoking were strongly associated with both
      physically and mentally unhealthy days among those with functional limitations.
      Among those without functional limitations, the direction of the effects was
      similar, but the size of the effects was substantially smaller. CONCLUSIONS: The
      availability of lower cost medical care, increasing leisure-time physical
      activity, and reducing rates of cigarette smoking will improve population HRQOL
      among older adults with and without functional limitations. These factors provide
      valuable information for determining future public health priorities.

PMID- 22390515
TI  - Stress and mental health among midlife and older gay-identified men.
AB  - OBJECTIVES: We investigated associations between stress and mental health
      (positive affect, depressive symptoms) among HIV-negative and HIV-positive
      midlife and older gay-identified men, along with the mediating and moderating
      effects of mastery and emotional support. We also studied the mental health
      effects of same-sex marriage. METHODS: We obtained data from self-administered
      questionnaires completed in 2009 or 2010 by a subsample (n = 202; average age =
      56.91 years; age range = 44-75 years) of participants in the University of
      California, Los Angeles component of the Multicenter AIDS Cohort Study, one of
      the largest and longest-running natural-history studies of HIV/AIDS in the United
      States. RESULTS: Both sexual minority stress (perceived gay-related stigma,
      excessive HIV bereavements) and aging-related stress (independence and fiscal
      concerns) appeared to have been detrimental to mental health. Sense of mastery
      partially mediated these associations. Being legally married was significantly
      protective net of all covariates, including having a domestic partner but not
      being married. Education, HIV status, and race/ethnicity had no significant
      effects. CONCLUSIONS: Sexual minority and aging-related stress significantly
      affected the emotional lives of these men. Personal sense of mastery may help to
      sustain them as they age. We observed specific mental health benefits of same-sex
      legal marriage.

PMID- 22390516
TI  - Project-based Housing First for chronically homeless individuals with alcohol
      problems: within-subjects analyses of 2-year alcohol trajectories.
AB  - OBJECTIVES: Two-year alcohol use trajectories were documented among residents in
      a project-based Housing First program. Project-based Housing First provides
      immediate, low-barrier, nonabstinence-based, permanent supportive housing to
      chronically homeless individuals within a single housing project. The study aim
      was to address concerns that nonabstinence-based housing may enable alcohol use.
      METHODS: A 2-year, within-subjects analysis was conducted among 95 chronically
      homeless individuals with alcohol problems who were allocated to project-based
      Housing First. Alcohol variables were assessed through self-report. Data on
      intervention exposure were extracted from agency records. RESULTS: Multilevel
      growth models indicated significant within-subjects decreases across alcohol use
      outcomes over the study period. Intervention exposure, represented by months
      spent in housing, consistently predicted additional decreases in alcohol use
      outcomes. CONCLUSIONS: Findings did not support the enabling hypothesis. Although
      the project-based Housing First program did not require abstinence or treatment
      attendance, participants decreased their alcohol use and alcohol-related problems
      as a function of time and intervention exposure.

PMID- 22390517
TI  - Feeding a family in a recession: food insecurity among Minnesota parents.
AB  - OBJECTIVES: We assessed current levels of food insecurity among a large, diverse
      sample of parents and examined associations between food insecurity and parental
      weight status, eating patterns, and the home food environment. METHODS: Project F
      EAT (Families and Eating and Activity Among Teens) examined the home food
      environments of adolescents. Parents and caregivers (n = 2095) living with
      adolescents from the Minneapolis-St. Paul, Minnesota school districts completed
      mailed surveys during a 12-month period in 2009-2010. We performed our
      assessments using multivariate regressions. RESULTS: Almost 39% of the parents
      and caregivers experienced household food insecurity, whereas 13% experienced
      very low food security. Food insecurity was significantly associated with poorer
      nutrition-related variables such as higher rates of parental overweight and
      obesity, less healthy foods served at meals, and higher rates of binge eating.
      Food-insecure parents were 2 to 4 times more likely to report barriers to
      accessing fruits and vegetables. CONCLUSIONS: Food insecurity was highly
      prevalent. Environmental interventions are needed to protect vulnerable families
      against food insecurity and to improve access to affordable, healthy foods.

PMID- 22390518
TI  - A 2-phase labeling and choice architecture intervention to improve healthy food
      and beverage choices.
AB  - OBJECTIVES: We assessed whether a 2-phase labeling and choice architecture
      intervention would increase sales of healthy food and beverages in a large
      hospital cafeteria. METHODS: Phase 1 was a 3-month color-coded labeling
      intervention (red = unhealthy, yellow = less healthy, green = healthy). Phase 2
      added a 3-month choice architecture intervention that increased the visibility
      and convenience of some green items. We compared relative changes in 3-month
      sales from baseline to phase 1 and from phase 1 to phase 2. RESULTS: At baseline
      (977,793 items, including 199,513 beverages), 24.9% of sales were red and 42.2%
      were green. Sales of red items decreased in both phases (P < .001), and green
      items increased in phase 1 (P < .001). The largest changes occurred among
      beverages. Red beverages decreased 16.5% during phase 1 (P < .001) and further
      decreased 11.4% in phase 2 (P < .001). Green beverages increased 9.6% in phase 1
      (P < .001) and further increased 4.0% in phase 2 (P < .001). Bottled water
      increased 25.8% during phase 2 (P < .001) but did not increase at 2 on-site
      comparison cafeterias (P < .001). CONCLUSIONS: A color-coded labeling
      intervention improved sales of healthy items and was enhanced by a choice
      architecture intervention.

PMID- 22390519
TI  - Life course outcomes on mental and physical health: the impact of foster care on
      adulthood.
AB  - OBJECTIVE: We compared the prevalence rates of mental health and physical health
      problems between adults with histories of childhood foster care and those
      without. METHODS: We used 2003-2005 California Health Interview Survey data (n =
      70,456) to test our hypothesis that adults with childhood histories of foster
      care will report higher rates of mental and physical health concerns, including
      those that affect the ability to work, than will those without. RESULTS: Adults
      with a history of childhood foster care had more than twice the odds of receiving
      Social Security Disability Insurance because they were unable to work owing to
      mental or physical health problems for the past year, even after stratifying by
      age and adjusting for demographic and socioeconomic characteristics. CONCLUSIONS:
      Childhood foster care may be a sentinel event, signaling the increased risk of
      adulthood mental and physical health problems. A mental and physical health care
      delivery program that includes screening and treatment and ensures follow-up for
      children and youths who have had contact with the foster care system may decrease
      these individuals' disproportionately high prevalence of poor outcomes throughout
      their adulthood.

PMID- 22390520
TI  - Association of returning to work with better health in working-aged adults: a
      systematic review.
AB  - OBJECTIVES: We systematically reviewed the literature on the impact of returning
      to work on health among working-aged adults. METHODS: We searched 6 electronic
      databases in 2005. We selected longitudinal studies that documented a transition
      from unemployment to employment and included a comparison group. Two reviewers
      independently appraised the retrieved literature for potential relevance and
      methodological quality. RESULTS: Eighteen studies met our inclusion criteria,
      including 1 randomized controlled trial. Fifteen studies revealed a beneficial
      effect of returning to work on health, either demonstrating a significant
      improvement in health after reemployment or a significant decline in health
      attributed to continued unemployment. We also found evidence for health
      selection, suggesting that poor health interferes with people's ability to go
      back to work. Some evidence suggested that earlier reemployment may be associated
      with better health. CONCLUSIONS: Beneficial health effects of returning to work
      have been documented in a variety of populations, times, and settings. Return-to
      work programs may improve not only financial situations but also health.

PMID- 22390521
TI  - Effects of timing and level of degree attained on depressive symptoms and self
      rated health at midlife.
AB  - OBJECTIVES: We examined whether attaining a higher educational degree after 25
      years of age was associated with fewer depressive symptoms and better self-rated
      health at midlife than was not attaining a higher educational degree. METHODS: We
      analyzed data from National Longitudinal Survey of Youth, restricting our sample
      to respondents who had not attained a bachelor's degree by 25 years of age (n =
      7179). We stratified all regression models by highest degree attained by 25 years
      of age. RESULTS: Among respondents with no degree, a high school diploma, or a
      post-high school certificate at 25 years of age, attaining at least a bachelor's
      degree by midlife was associated with fewer depressive symptoms and better self
      rated health at midlife compared with respondents who did not attain a higher
      degree by midlife. Those with an associate's degree at 25 years of age who later
      attained a bachelor's degree or higher reported better health at midlife.
      CONCLUSIONS: Attaining at least a bachelor's degree after 25 years of age is
      associated with better midlife health. Other specifications of educational timing
      and its health effects across the life course should be studied.

PMID- 22390523
TI  - Public health surveillance and meaningful use regulations: a crisis of
      opportunity.
AB  - The Health Information Technology for Economic and Clinical Health Act is
      intended to enhance reimbursement of health care providers for meaningful use of
      electronic health records systems. This presents both opportunities and
      challenges for public health departments.  To earn incentive payments, clinical
      providers must exchange specified types of data with the public health system,
      such as immunization and syndromic surveillance data and notifiable disease
      reporting. However, a crisis looms because public health's information technology
      systems largely lack the capabilities to accept the types of data proposed for
      exchange.  Cloud computing may be a solution for public health information
      systems. Through shared computing resources, public health departments could reap
      the benefits of electronic reporting within federal funding constraints.

PMID- 22390524
TI  - Population burden of betel quid abuse and its relation to oral premalignant
      disorders in South, Southeast, and East Asia: an Asian Betel-quid Consortium
      Study.
AB  - OBJECTIVES: We investigated the population burden of betel quid abuse and its
      related impact on oral premalignant disorders (OPDs) in South, Southeast, and
      East Asia. METHODS: The Asian Betel-Quid Consortium conducted a multistage
      sampling of 8922 representative participants from Taiwan, Mainland China,
      Malaysia, Indonesia, Nepal, and Sri Lanka. Participants received an interviewer
      administered survey and were examined for oral mucosal disorders. RESULTS: The
      prevalence of betel quid abuse was 0.8% to 46.3% across 6 Asian populations. The
      abuse frequency was over 40.5% for current chewers, with the highest proportion
      in Nepalese and Southeast Asian chewers (76.9%-99.6%). Tobacco-added betel quid
      conferred higher abuse rates (74.4%-99.6%) among Malaysian, Indonesian, and Sri
      Lankan men than did tobacco-free betel quid (21.8%-89.1%). Gender, lower
      education level, younger age at chewing initiation, and clustering of familial
      betel quid use significantly contributed to higher abuse rates. Indonesian betel
      quid abusers showed the highest prevalence of OPDs and had a greater risk of OPDs
      than did nonabusers. CONCLUSIONS: Betel quid abuse is high in regions of Asia
      where it is customarily practiced, and such abuse correlates highly with OPDs. By
      recognizing abuse-associated factors, health policies and preventive frameworks
      can be effectively constructed to combat these oral preneoplasms.

PMID- 22390527
TI  - Regarding: long-term results of percutaneous lumbar decompression mild for spinal
      stenosis.

PMID- 22390525
TI  - Socioeconomic disparities in community-based treatment of tobacco dependence.
AB  - OBJECTIVES: We examined socioeconomic disparities in a community-based tobacco
      dependence treatment program. METHODS: We provided cognitive-behavioral treatment
      and nicotine patches to 2739 smokers. We examined treatment use, clinical and
      environmental, and treatment outcome differences by socioeconomic status (SES).
      We used logistic regressions to model end-of-treatment and 3- and 6-month
      treatment outcomes. RESULTS: The probability of abstinence 3 months after
      treatment was 55% greater for the highest-SES than for the lowest-SES (adjusted
      odds ratio [AOR] = 1.55; 95% confidence interval [CI] = 1.03, 2.33) smokers and
      increased to 2.5 times greater for the highest-SES than for the lowest-SES
      smokers 6 months after treatment (AOR = 2.47; 95% CI = 1.62, 3.77). Lower-SES
      participants received less treatment content and had fewer resources and
      environmental supports to manage a greater number of clinical and environmental
      challenges to abstinence. CONCLUSIONS: Targets for enhancing therapeutic
      approaches for lower socioeconomic groups should include efforts to ensure that
      lower-SES groups receive more treatment content, strategies to address specific
      clinical and environmental challenges associated with treatment outcomes for
      lower-SES smokers (i.e., higher dependence and stress levels and exposure to
      other smokers), and strategies to provide longer-term support.

PMID- 22390528
TI  - Factors contributing to psychoaffective differences among men with sexual
      dysfunction in response to a partnered sexual experience.
AB  - Even though men with sexual dysfunction, as a whole, experience less positive and
      more negative emotion to sexual situations than do men without sexual
      dysfunction, men with sexual dysfunction themselves show considerable differences
      in their emotional responses. The authors explored a set of a priori factors that
      might contribute to the emotional response of men with sexual dysfunction in the
      context of a partnered sexual experience. The authors constructed 5 global
      affective response factors-2 positive and 3 negative-through principle components
      analysis and related them to 5 independent predictor variables in a sample of 66
      men with sexual dysfunction visiting a urology clinic. Predictor variables
      included the following: dysfunction severity, cardiovascular/metabolic health,
      age, self-reported importance of sex, and perceived importance of sex to the
      partner. The affective factor, apprehension, was the most sensitive of the 5
      derived emotional response factors, with most predictor variables significantly
      affecting this factor. However, of the predictor variables, the self-rated
      importance of sex to the patient and the perceived importance of sex to the
      partner were most strongly related to the affective factors. These findings
      suggest that, no matter the etiology, the therapeutic strategy should include
      attention to men's emotional experiences associated with sexual activity by
      addressing individual and partner expectations, self-efficacy, and communication
      in the sexual relationship.

PMID- 22390529
TI  - Challenging atrophied perspectives on postmenopausal dyspareunia: a systematic
      description and synthesis of clinical pain characteristics.
AB  - This study investigated the clinical attributes of postmenopausal dyspareunia.
      The authors obtained a systematic description of pain symptomatology from 182
      postmenopausal dyspareunia sufferers using a structured interview, quantitative
      sensory testing, a standardized pain measure, and gynecological examination. The
      authors conducted a cluster analysis to examine whether sufferers could be
      categorized using clinical pain and gynecological factors. The authors delineated
      6 subgroups, each exhibiting distinct combinations of pain and gynecological
      characteristics. The results support the hypothesis that, similarly to
      premenopausal dyspareunia, postmenopausal dyspareunia is a heterogeneous
      condition.

PMID- 22390530
TI  - Demographics, behavior problems, and psychosexual characteristics of adolescents
      with gender identity disorder or transvestic fetishism.
AB  - This study provided a descriptive and quantitative comparative analysis of data
      from an assessment protocol for adolescents referred clinically for gender
      identity disorder (n = 192; 105 boys, 87 girls) or transvestic fetishism (n =
      137, all boys). The protocol included information on demographics, behavior
      problems, and psychosexual measures. Gender identity disorder and transvestic
      fetishism youth had high rates of general behavior problems and poor peer
      relations. On the psychosexual measures, gender identity disorder patients had
      considerably greater cross-gender behavior and gender dysphoria than did
      transvestic fetishism youth and other control youth. Male gender identity
      disorder patients classified as having a nonhomosexual sexual orientation (in
      relation to birth sex) reported more indicators of transvestic fetishism than did
      male gender identity disorder patients classified as having a homosexual sexual
      orientation (in relation to birth sex). The percentage of transvestic fetishism
      youth and male gender identity disorder patients with a nonhomosexual sexual
      orientation self-reported similar degrees of behaviors pertaining to transvestic
      fetishism. Last, male and female gender identity disorder patients with a
      homosexual sexual orientation had more recalled cross-gender behavior during
      childhood and more concurrent cross-gender behavior and gender dysphoria than did
      patients with a nonhomosexual sexual orientation. The authors discuss the
      clinical utility of their assessment protocol.

PMID- 22390531
TI  - Agomelatine: an antidepressant without deterioration of sexual response.
AB  - Sexual dysfunctions caused by the use of antidepressants are relatively common.
      Agomelatine has demonstrated antidepressant properties in comparative studies
      with sertraline, fluoxetine, and venlafaxine as active controls. The aim of this
      study was to evaluate the effects of agomelatine on sexual response. Acutely
      depressed patients (n = 25) treated with agomelatine (25-50 mg/day) were
      evaluated over 12 weeks. Agomelatine showed a favorable response on depressive
      symptoms using the Montgomery-Asberg Depression Rating Scale throughout the
      study. The Clinical Global Impression improvement score at the end of the study
      was 1.70 (SD = 0.89). The author assessed sexual response using the Arizona
      Sexual Experiences Scale, the International Index of Erectile Function, and a
      Visual Analogue Scale for desire, arousal, time, and intensity of orgasm and
      vaginal lubrication. Arizona Sexual Experiences Scale scores improved after 3
      weeks of treatment, mainly attributable to an improvement in women rather than in
      men. The Visual Analogue Scale showed improvement in all stages of sexual
      response in women, with minimal changes in men. Clinical Satisfaction Scores at
      the end of the study for all patients were 7.00 (SD = 1.53). In conclusion,
      agomelatine appears to be a good option for the treatment of depression because
      it would not have adverse effects on sexual function.

PMID- 22390532
TI  - Gender differences in desire discrepancy as a predictor of sexual and
      relationship satisfaction in a college sample of heterosexual romantic
      relationships.
AB  - The authors examined desire discrepancy and its effect on sexual and relationship
      satisfaction in a sample of 133 heterosexual couples attending a midsize
      university. Couples were required to be in a relationship for at least 1 year (M
      = 4.32 years, SD = 3.13 years); 23.7% of the couples were cohabitating.
      Hierarchical multiple regression results indicated that higher desire discrepancy
      scores significantly predicted women's (but not men's) lower sexual satisfaction
      after controlling for relationship satisfaction. Higher desire discrepancy scores
      significantly predicted men's (but not women's) lower relationship satisfaction
      after controlling for sexual satisfaction. The authors assessed gender
      differences using a mixed model with the dyad and gender as factors and
      satisfaction as the outcome. Although gender difference patterns appeared in the
      regression models, the differences were nonsignificant within each couple in the
      extent to which desire discrepancy affected sexual and relationship satisfaction.
      These findings suggest moving away from focusing on only one partner with low
      desire and shifting attention to the dyad's interaction. Also, the way in which
      desire discrepancy affects sexual and relationship satisfaction deserves
      consideration. Therapeutic implications and study limitations are discussed.

PMID- 22390536
TI  - Genetic polymorphisms and recurrent spontaneous abortions: an overview of current
      knowledge.
AB  - The relevance of gene polymorphisms in the development of unexplained recurrent
      spontaneous abortion is still unclear. Cytokines, angiogenic mediators, and
      hormones are involved in all stages of reproduction and pregnancy outcome.
      Impaired production and/or unbalanced ratios of these mediators have been
      implicated in the pathogenesis of unexplained recurrent spontaneous abortion.
      Functional polymorphism influence gene activity and therefore can interfere with
      the expression of mediators. Several studies have been carried out to evaluate
      the relationship between cytokines, angiogenic mediators, and hormones gene
      polymorphisms and unexplained recurrent spontaneous abortion. The results of
      these studies are mostly contradictory, and few significant associations have
      been identified. Up to present time, the evidence is insufficient to support the
      evaluation of cytokines, angiogenic mediators, and hormones gene polymorphism in
      routine workup in all cases of recurrent pregnancy loss, and these tests are not
      included in any of the major obstetric guidelines.

PMID- 22390537
TI  - "Left at right" adult liver transplantation: the feasibility of heterotopic
      implantation of left liver graft.
AB  - Left liver grafts have been widely utilized in adult liver transplantation (LT)
      and yielded acceptable results. However, the conventional orthotopic implantation
      of a left liver graft imposes the potential risk of perioperative vascular
      complications. We report herein an alternative modified technique for adult left
      liver LT and evaluate its feasibility in LT. In this study, 10 recipients had
      their left liver graft rotated 180 degrees , and heterotopically implanted at the
      right subphrenic space, which we termed "left at right" liver transplantation
      (LAR-LT). The sequence of vascular and biliary reconstruction was performed as
      standard techniques, and no perioperative vascular complications related to LAR
      LT were encountered. There were two mortalities in this series, one due to a
      small-for-size graft dysfunction and the other due to postoperative internal
      hemorrhage. Two recipients had biliary strictures that were successfully managed
      by percutaneous biliary dilatation and Roux-en-Y hepaticojejunostomy. The
      clinical characteristics and outcomes of patients undergoing LAR-LT were also
      compared with patients undergoing conventional orthotopic left liver LT (n = 14).
      Although the results showed no significant difference between the two groups,
      according to our experience, the satisfactory outcome and easier technical
      reconstruction suggest that the LAR-LT modification could be a feasible
      alternative to left liver LT.

PMID- 22390539
TI  - Intralesional therapy for psoriasis.
AB  - Localized resistant plaques of psoriasis often remain despite highly effective
      anti-psoriasis treatment. Intralesional therapy is often used to treat various
      malignant, infectious or inflammatory cutaneous diseases, including psoriasis.
      Despite the presence of many review articles on the treatment of psoriasis, no
      articles exist which review the use of intralesional therapy for psoriasis. In
      this article, we review the published literatures of intralesional therapy for
      psoriasis. Corticosteroids, methotrexate, cyclosporin, biologics, botulinum toxin
      type-A, 15-hydroxyeicosatetraenoic acid, and chemotherapy agents such as 5
      fluorouracil are discussed. Also, agents which may be used intralesionally and
      have the potential to treat psoriasis will also be reviewed such as bleomycin,
      vincristine or vinblastine, mitomycin-C, aminophylline, 5-aminolevulinic acid,
      rituximab, bevacizumab and pentoxifylline are included.

PMID- 22390538
TI  - 3,5-Diaryl-2-aminopyridines as a novel class of orally active antimalarials
      demonstrating single dose cure in mice and clinical candidate potential.
AB  - A novel class of orally active antimalarial 3,5-diaryl-2-aminopyridines has been
      identified from phenotypic whole cell high-throughput screening of a commercially
      available SoftFocus kinase library. The compounds were evaluated in vitro for
      their antiplasmodial activity against K1 (chloroquine and drug-resistant strain)
      and NF54 (chloroquine-susceptible strain) as well as for their cytotoxicity.
      Synthesis and structure-activity studies identified a number of promising
      compounds with selective antiplasmodial activity. One of these frontrunner
      compounds, 15, was equipotent across the two strains (K1 = 25.0 nM, NF54 = 28.0
      nM) and superior to chloroquine in the K1 strain (chloroquine IC(50) K1 = 194.0
      nM). Compound 15 completely cured Plasmodium berghei-infected mice with a single
      oral dose of 30 mg/kg. Dose-response studies generated ED(50) and ED(90) values
      of 0.83 and 1.74 mg/kg for 15 in the standard four-dose Peters test.
      Pharmacokinetic studies in the rat indicated that this compound has good oral
      bioavailability (51% at 20 mg/kg) and a reasonable half-life (t(1/2) ~ 7-8 h).

PMID- 22390540
TI  - Confocal microscopy analysis of breech face marks on fired cartridge cases from
      10 consecutively manufactured pistol slides.
AB  - Recent publications from the National Academy of Sciences have called for
      additional foundational research in the field of firearm and toolmark analysis.
      We examined test fires from 10 pistol slides with consecutively manufactured
      breech faces. A total of nine test fires from each pistol slide, for a total of
      90 test fired cartridge cases, were compared using confocal microscopy combined
      with three-dimensional cross-correlation analysis algorithms. A total of 8010
      comparisons were performed (720 matches and 7290 nonmatches). The average score
      for matches was 0.82 with a standard deviation of 0.06. The average score for
      nonmatches was 0.20 with a standard deviation of 0.03. Additionally, subclass
      toolmarks were observed on the breech faces, but the presence of subclass was not
      detected in the correlation analysis. There was no overlap of scores between
      matching and nonmatching test fires. This provides objective data that support
      the AFTE (Association of Firearms and Tool Mark Examiners) theory of
      identification.

PMID- 22390541
TI  - Analysis of energy use and CO2 emissions in the U.S. refining sector, with
      projections for 2025.
AB  - This analysis uses linear programming modeling of the U.S. refining sector to
      estimate total annual energy consumption and CO(2) emissions in 2025, for four
      projected U.S. crude oil slates. The baseline is similar to the current U.S.
      crude slate; the other three contain larger proportions of higher density, higher
      sulfur crudes than the current or any previous U.S. crude slates. The latter
      cases reflect aggressive assumptions regarding the volumes of Canadian crudes in
      the U.S. crude slate in 2025. The analysis projects U.S. refinery energy use 3.7%
      6.3% (~ 0.13-0.22 quads/year) higher and refinery CO(2) emissions 5.4%-9.3% (~
      0.014-0.024 gigatons/year) higher in the study cases than in the baseline.
      Refining heavier crude slates would require significant investments in new
      refinery processing capability, especially coking and hydrotreating units. These
      findings differ substantially from a recent estimate asserting that processing
      heavy oil or bitumen blends could increase industry CO(2) emissions by 1.6-3.7
      gigatons/year.

PMID- 22390542
TI  - Radiation products at 77 K in trehalose single crystals: EMR and DFT analysis.
AB  - The radicals obtained in trehalose dihydrate single crystals after 77 K X
      irradiation have been investigated at the same temperature using X-band electron
      paramagnetic resonance (EPR), electron nuclear double resonance (ENDOR), and
      ENDOR-induced EPR (EIE) techniques. Five proton hyperfine coupling tensors were
      unambiguously determined from the ENDOR measurements and assigned to three carbon
      centered radical species (T1, T1*, and T2) based on the EIE spectra. EPR angular
      variations revealed the presence of four additional alkoxy radical species (T3 to
      T6) and allowed determination of their g tensors. Using periodic density
      functional theory (DFT) calculations, T1/T1*, T2, and T3 were identified as H
      loss species centered at C4, C1', and O2', respectively. The T4 radical is
      proposed to have the unpaired electron at O4, but considerable discrepancies
      between experimental and calculated HFC values indicate it is not simply the
      (net) H-loss species. No suitable models were found for T5 and T6. These exhibit
      a markedly larger g anisotropy than T3 and T4, which were not reproduced by any
      of our DFT calculations.

PMID- 22390545
TI  - Hypogalactosylation of serum N-glycans fails to predict clinical response to
      methotrexate and TNF inhibition in rheumatoid arthritis.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is associated with hypogalactosylation of
      immunoglobulin G (IgG). We examined whether a proxy measure for galactosylation
      of IgG N-glycans could predict response to therapy or was differentially affected
      by methotrexate (MTX) or TNF blockade. METHODS: Using a previously defined normal
      phase high-performance liquid chromatography approach, we ascertained the
      galactosylation status of whole serum N-glycans in two well-defined RA clinical
      cohorts: the Autoimmune Biomarkers Collaborative Network (n = 98) and Nested I (n
      = 64). The ratio of agalactosylated to monogalactosylated N-glycans in serum
      (sG0/G1) was determined before and during therapy with MTX or TNF inhibition and
      correlated with anticitrullinated peptide antibody (ACPA) status and clinical
      response as assessed by 28-joint Disease Activity Score utilizing C-reactive
      peptide and European League Against Rheumatism response criteria. RESULTS: RA
      patients from both cohorts exhibited elevation of sG0/G1 at baseline. Improvement
      in clinical scores correlated with a reduction in sG0/G1 (Spearman's rho = 0.31
      to 0.37; P < 0.05 for each cohort). However, pretreatment sG0/G1 was not
      predictive of clinical response. Changes in sG0/G1 were similar in the MTX and
      TNF inhibitor groups. Corrected for disease activity, ACPA positivity correlated
      with higher sG0/G1. CONCLUSIONS: Baseline serum N-glycan hypogalactosylation, an
      index previously correlated with hypogalactosylation of IgG N-glycans, did not
      distinguish patients with rheumatoid arthritis who were likely to experience a
      favorable clinical response to MTX or TNF blockade. Clinical improvement was
      associated with partial glycan normalization. ACPA-positive patients demonstrated
      enhanced N-glycan aberrancy compared with ACPA-negative patients.

PMID- 22390544
TI  - Enhanced epimerization of glycosylated amino acids during solid-phase peptide
      synthesis.
AB  - Glycopeptides are extremely useful for basic research and clinical applications,
      but access to structurally defined glycopeptides is limited by the difficulties
      in synthesizing this class of compounds. In this study, we demonstrate that many
      common peptide coupling conditions used to prepare O-linked glycopeptides result
      in substantial amounts of epimerization at the alpha position. In fact,
      epimerization resulted in up to 80% of the non-natural epimer, indicating that it
      can be the major product in some reactions. Through a series of mechanistic
      studies, we demonstrate that the enhanced epimerization relative to
      nonglycosylated amino acids is due to a combination of factors, including a
      faster rate of epimerization, an energetic preference for the unnatural epimer
      over the natural epimer, and a slower overall rate of peptide coupling. In
      addition, we demonstrate that use of 2,4,6-trimethylpyridine (TMP) as the base in
      peptide couplings produces glycopeptides with high efficiency and low
      epimerization. The information and improved reaction conditions will facilitate
      the preparation of glycopeptides as therapeutic compounds and vaccine antigens.

PMID- 22390546
TI  - LC-MS analysis of polyclonal human anti-Neu5Gc xeno-autoantibodies immunoglobulin
      G Subclass and partial sequence using multistep intravenous immunoglobulin
      affinity purification and multienzymatic digestion.
AB  - Human polyclonal IgG antibodies directly against the nonhuman sialic acid N
      glycolylneuraminic acid (Neu5Gc) are potential biomarkers and mechanistic
      contributors to cancer and other diseases associated with chronic inflammation.
      Using a sialoglycan microarray, we screened the binding pattern of such
      antibodies (anti-Neu5Gc IgG) in several samples of clinically approved human IVIG
      (IgG). These results were used to select an appropriate sample for a multistep
      affinity purification of the xeno-autoantibody fraction. The sample was then
      analyzed via our multienzyme digestion procedure followed by nano liquid
      chromatography (nanoLC) coupled to linear ion trap-Fourier transform mass
      spectrometry (LTQ-FTMS). We used characteristic and unique peptide sequences to
      determine the IgG subclass distribution and thus provided direct evidence that
      all four IgG subclasses can be generated during a xeno-autoantibody immune
      response to carbohydrate Neu5Gc-antigens. Furthermore, we obtained a significant
      amount of sequence coverage of both the constant and variable regions. The
      approach described here, therefore, provides a way to characterize these
      clinically significant antibodies, helping to understand their origins and
      significance.

PMID- 22390548
TI  - Relationship between normal serum creatinine concentration and periodontal
      disease in Japanese middle-aged males.
AB  - BACKGROUND: Periodontitis has been shown to be closely related to diabetes, which
      was recently found to be associated with lower serum creatinine. Conversely,
      several studies have suggested a positive relationship between periodontitis and
      abnormally high concentrations of serum creatinine associated with renal
      dysfunction, seemingly contradicting the above. This study evaluates periodontal
      status and serum levels of creatinine within the normal range to resolve this
      apparent contradiction. METHODS: A comprehensive health examination of 907
      Japanese males, 49 to 59 years old, was performed from 2000 to 2002. A blood
      sample was collected from the antecubital vein after an overnight fast. The
      periodontal parameters were periodontal probing depth (PD) and clinical
      attachment loss (AL). We examined the association between serum creatinine
      concentration within the normal range and periodontal parameters. RESULTS: Serum
      creatinine concentration within the normal range was inversely correlated with
      mean PD and mean AL. In multivariate linear regression analyses, every 0.1-mg/dL
      increment in serum creatinine concentration was associated with a 0.064-mm
      decrease in both mean PD and mean AL (P <0.05) after adjusting for confounding
      variables. CONCLUSION: This study finds a significant inverse association between
      normal serum creatinine concentration and periodontal disease.

PMID- 22390549
TI  - Accuracy of linear measurements and visibility of the mandibular canal of cone
      beam computed tomography images with different voxel sizes: an in vitro study.
AB  - BACKGROUND: The major use of cone-beam computed tomography (CBCT) is in implant
      planning. Although CBCT has been shown to be a reliable tool for measurements, we
      were unable to find studies comparing the differences between images acquired
      using different voxel sizes for implant planning. The aims of the present in
      vitro study are to verify the accuracy of linear measurements and to analyze the
      visibility of the mandibular canal on CBCT images obtained using different voxel
      sizes. METHODS: Twelve dry human hemimandibles were scanned using voxel sizes of
      0.2, 0.3, and 0.4 mm, and 108 transversal CBCT images were generated, on which
      two examiners performed 648 linear measurements and evaluated the visibility of
      the mandibular canal. RESULTS: The global mean +/- SD error between measurements
      on images and direct measurements was 0.23 +/- 0.20 mm. CBCT measurements
      underestimated direct measurements in 390 cases (60.2%). All measurement errors
      found were <1 mm. There was a statistically significant difference (P = 0.0001
      and P = 0.0028) between the two examiners only when measuring the width in two
      posterior sites. There was a statistically significant difference (P = 0.0242)
      between voxel sizes only for one of the examiners, for a measurement of height.
      It was possible to visualize the mandibular canal in all of the 108 images
      evaluated. CONCLUSIONS: Transversal CBCT images are adequate for linear
      measurements in the posterior region of the mandible and provide adequate
      visualization of the mandibular canal using voxel sizes of 0.2, 0.3, or 0.4 mm. A
      voxel of 0.3 mm is a good compromise between image quality and low radiation
      dose.

PMID- 22390550
TI  - Treatment of localized gingival recessions using gingival unit grafts: a
      randomized controlled clinical trial.
AB  - BACKGROUND: One of the success factors in periodontal plastic surgery is the
      synergistic relationship between involved tissues and vascular supply. Gingiva as
      a functional unit is unique with a specific vascular configuration and contains
      the supracrestal portion naturally created to survive over avascular root
      surfaces. The aim of this randomized controlled trial is to clinically evaluate
      the treatment of localized gingival recessions by using gingival unit grafts
      (palatal tissue involving marginal gingiva and papillae) compared with
      conventional palatal grafts. METHODS: Seventeen patients with Class I to II
      recession defects on mandibular anterior teeth were included and randomly divided
      into two groups. Recessions were treated with gingival unit grafts in group 1 (n
      = 8) and with palatal grafts in group 2 (n = 9). Clinical parameters including
      vertical recession (VR), probing depth, keratinized tissue (KT), and attachment
      level were recorded at baseline and 8 months after surgery. RESULTS: Both
      treatments produced significant clinical improvements within the groups.
      Intergroup comparison revealed significantly higher VR reduction, attachment, and
      KT gain in group 1 than in group 2; mean percentages of the defect coverage were
      91.62% +/- 9.74% and 68.97% +/- 13.67%, respectively (P <0.05). Healing of the
      gingival unit donor site was uneventful. CONCLUSION: Within its limits, this
      study demonstrates the possibility of treating buccal recessions with gingival
      unit grafts as an alternative technique using gingival donor graft of site
      specific vascular configuration, with better defect coverage, clinical, and
      esthetic improvements compared with palatal grafts.

PMID- 22390551
TI  - Translation of pharmacogenetics to clinical practice: what will it take?

PMID- 22390552
TI  - Nanomedicine on the move: from monotherapeutic regimens to combination therapies.

PMID- 22390555
TI  - Octreotide long-acting repeatable for acromegaly.
AB  - Acromegaly remains a therapeutic challenge for the endocrinologist. Among the
      available therapeutic options, octreotide long-acting repeatable
      (Sandostatin((r)) LAR((r)), Novartis) plays a chief role, both as a primary
      therapy and as an adjuvant treatment after unsuccessful surgery. A plethora of
      papers and a meta-analysis have demonstrated its efficacy in: control of clinical
      picture; achievement of safe growth hormone and normal age-matched IGF-I levels
      (both factors associated with restoration of normal life expectancy) in 60-70% of
      patients; control of tumor volume (with real shrinkage in over half of cases);
      and halt or reversal of most acromegaly-associated comorbidities. Treatment is
      well tolerated in most patients and can be safely prolonged for many years if
      required.

PMID- 22390556
TI  - Recent progress in unraveling the complexities of receptor biology: towards new
      therapeutics.
AB  - This meeting is the main annual event convened by the British Pharmacological
      Society. The December 2011 meeting featured a joint symposium with the Chinese
      Pharmacological Society. Held at the Queen Elizabeth II conference centre in
      London, UK, the meeting was sold out, with more than 800 delegates in attendance.
      The meeting comprised a diverse selection of symposia, together with award
      lectures, short oral communications and vibrant poster sessions, in both basic
      and clinical pharmacology.

PMID- 22390554
TI  - Mesalamine in the treatment and maintenance of remission of ulcerative colitis.
AB  - Ulcerative colitis (UC) is a chronic disease of the GI tract that is
      characterized by mucosal inflammation in the colon. Mesalamine (mesalazine) is a
      5-aminosalicylic acid compound that is the first-line treatment for patients with
      mild-to-moderate UC. There are multiple formulations of mesalamine available,
      primarily differentiated by their means of delivering active mesalamine to the
      colon. Mesalamine has been demonstrated in randomized controlled trials to induce
      both clinical response and remission, and maintain clinical remission, in these
      patients. It has few serious adverse effects and is generally well tolerated by
      patients. The main areas of uncertainty with use of mesalamine in patients with
      UC center on the optimal dose for induction of response, how to maintain patient
      adherence and the role of mesalamine in cancer chemoprophylaxis. Generic forms of
      mesalamine have yet to be approved by regulatory bodies in the USA.

PMID- 22390557
TI  - Meeting the obligation to communicate clinical trial results to study volunteers.
AB  - Although the overwhelming majority of study volunteers want to receive
      information on the results of their participation in clinical trials, research
      suggests that most study volunteers never do. CISCRP - an independent nonprofit
      organization - in collaboration with Pfizer, conducted a study evaluating the
      feasibility and impact of a new process to inform study volunteers of the results
      of their clinical trials. Two process components were evaluated via surveys,
      focus groups, and interviews with volunteers and investigative site staff: a
      series of ongoing post-trial communications to set expectations for when trial
      results would be received; and routine development and delivery of the lay
      language trial results summary. The results of this assessment show that study
      volunteers and investigative site staff are extremely receptive to receiving
      clinical trial results and that the process of preparing and disseminating
      clinical trial results is feasible and generally easy to execute. The results
      also indicate that study volunteer comprehension of basic facts about their
      clinical trial pre- and post-test increased by as much as 65.6 percentage points,
      and suggest that this communication initiative may positively impact volunteer
      recruitment, retention and long-term trust in the clinical research enterprise.

PMID- 22390558
TI  - Drug discovery and development: lessons from an undeveloped drug.
AB  - In this article, drug discovery and preclinical development paradigms, as
      employed in today's pharmaceutical companies, are discussed. The antimalarial
      drug, artemisinin, is given as an example of a compound that is unlikely to be
      developed by a modern pharmaceutical company, yet is a safe and effective drug
      for the treatment of a deadly disease. It is argued that the use of prespecified
      charts, listing undesired properties to deselect molecules may lead to missed
      opportunities in bringing best-in-class medications to patients. Implementation
      of systems pharmacology, disease progression and pharmacokinetic/pharmacodynamic
      models are proposed. These models offer a superior approach in selecting the best
      drug candidates with the highest chance of success of entry into the market.

PMID- 22390559
TI  - Do the benefits of anti-arrhythmic drugs outweigh the associated risks? A tale of
      treatment goals in atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common cardiac rhythm disorder and places a
      substantial burden on the US healthcare system. Unfortunately, there is no
      consensus as to whether patients should be treated with a primary rate- or rhythm
      control strategy. The use of anti-arrhythmic drugs in the treatment of AF is
      discussed in the broader context of AF disease-management strategies with a focus
      on rhythm control. Outside of rhythm/ECG, AF treatment targets and cardiovascular
      outcomes are highlighted.

PMID- 22390561
TI  - The use of STOPP/START criteria as a screening tool for assessing the
      appropriateness of medications in the elderly population.
AB  - Although numerous initiatives and interventions have been developed to promote
      medication safety, medication incidents still remain an important cause of
      hospitalization. To avoid this, it is important for physicians to prescribe
      safely. To date, the Beers criteria have been the most widely used explicit
      criteria for assessing the appropriateness of medications in the elderly, but
      they do have limitations. The more recent STOPP/START criteria were developed in
      the hope of addressing the deficiencies observed in the Beers criteria. This
      article gives an overview of STOPP/START criteria and its applications, and
      reviews the studies that assessed medication appropriateness using STOPP/START
      and/or the Beers criteria.

PMID- 22390562
TI  - Targeting adenosine receptors in the development of cardiovascular therapeutics.
AB  - Adenosine receptor stimulation has negative inotropic and dromotropic actions,
      reduces cardiac ischemia-reperfusion injury and remodeling, and prevents cardiac
      arrhythmias. In the vasculature, adenosine modulates vascular tone, reduces
      infiltration of inflammatory cells and generation of foam cells, and may prevent
      the development of atherosclerosis as a result. Modulation of insulin sensitivity
      may further add to the anti-atherosclerotic properties of adenosine signaling. In
      the kidney, adenosine plays an important role in tubuloglomerular feedback and
      modulates tubular sodium reabsorption. The challenge is to take advantage of the
      beneficial actions of adenosine signaling while preventing its potential adverse
      effects, such as salt retention and sympathoexcitation. Drugs that interfere with
      adenosine formation and elimination or drugs that allosterically enhance specific
      adenosine receptors seem to be most promising to meet this challenge.

PMID- 22390563
TI  - Treatment of interstitial lung diseases associated with connective tissue
      diseases.
AB  - A variety of interstitial lung diseases (ILDs) have been reported in association
      with connective tissue diseases (CTDs). ILD is commonly associated with multiple
      CTDs and accounts for significant morbidity and mortality in these conditions. In
      rheumatoid arthritis and systemic sclerosis, ILD commonly occurs in the course of
      these disorders (incidence: 20-44%). The pathological findings of ILDs are
      similar to those of idiopathic interstitial pneumonia. A wide variety of
      histopathologic features, such as various types of interstitial pneumonia and
      airway involvement, have been observed that are specific for ILDs in rheumatoid
      arthritis, and this high variety makes its pathology complicated. The diagnosis
      of ILD is generally based on clinical presentation, bronchioalveolar lavage fluid
      and high-resolution computed tomography, among others. The most important
      differential diagnosis is infection, especially pneumocystis pneumonia, and
      treatment-related toxic damage. The immunosuppressive agents most widely used for
      the treatment of ILDs are cyclophosphamide, azathioprine, mycophenolate mofetil
      and calcineurin inhibitors. Other therapeutic strategies are currently being
      extensively studied, such as antifibrotic agents, endothelin-1 receptor
      antagonists, tyrosine kinase inhibitors and newer biological agents. In this
      article, we describe novel therapies for ILDs associated with CTDs.

PMID- 22390560
TI  - Magnetic nanoparticles: an emerging technology for malignant brain tumor imaging
      and therapy.
AB  - Magnetic nanoparticles (MNPs) represent a promising nanomaterial for the targeted
      therapy and imaging of malignant brain tumors. Conjugation of peptides or
      antibodies to the surface of MNPs allows direct targeting of the tumor cell
      surface and potential disruption of active signaling pathways present in tumor
      cells. Delivery of nanoparticles to malignant brain tumors represents a
      formidable challenge due to the presence of the blood-brain barrier and
      infiltrating cancer cells in the normal brain. Newer strategies permit better
      delivery of MNPs systemically and by direct convection-enhanced delivery to the
      brain. Completion of a human clinical trial involving direct injection of MNPs
      into recurrent malignant brain tumors for thermotherapy has established their
      feasibility, safety and efficacy in patients. Future translational studies are in
      progress to understand the promising impact of MNPs in the treatment of malignant
      brain tumors.

PMID- 22390565
TI  - Enhancing performance of ZnO dye-sensitized solar cells by incorporation of
      multiwalled carbon nanotubes.
AB  - A low-temperature, direct blending procedure was used to prepare composite films
      consisting of zinc oxide [ZnO] nanoparticles and multiwalled carbon nanotubes
      [MWNTs]. The mesoporous ZnO/MWNT films were fabricated into the working
      electrodes of dye-sensitized solar cells [DSSCs]. The pristine MWNTs were
      modified by an air oxidation or a mixed acid oxidation treatment before use. The
      mixed acid treatment resulted in the disentanglement of MWNTs and facilitated the
      dispersion of MWNTs in the ZnO matrix. The effects of surface property and
      loading of MWNTs on DSSC performance were investigated. The performance of DSSCs
      was found to depend greatly on the type and the amount of MWNTs incorporated. At
      a loading of 0.01 wt%, the acid-treated MWNTs were able to increase the power
      conversion efficiency of fabricated cells from 2.11% (without MWNTs) to 2.70%.

PMID- 22390566
TI  - Thrombocytosis: a retrospective study of 165 dogs.
AB  - BACKGROUND: Thrombocytosis has been associated with various conditions, including
      inflammation, neoplasia, iron deficiency, splenectomy, and drug administration.
      OBJECTIVE: The aim of this study was to characterize diseases and conditions
      associated with thrombocytosis in dogs. METHODS: In this retrospective study,
      dogs with thrombocytosis (platelet count > 600 * 10(3) /MUL) and complete medical
      records during a 1-year period were included, and breed, sex, age, CBC results,
      alkaline phosphatase and gamma-glutamyltransferase activities in some dogs,
      administration of glucocorticoids or vincristine, and primary diagnosis were
      evaluated. RESULTS: Thrombocytosis was found in 240 of 5342 dogs (4.6%), and 165
      (3.1%) met inclusion criteria. Thrombocytosis was secondary in all dogs, and
      underlying diseases and conditions (n,%) were neoplasia (56, 33.9%), inflammation
      (55, 33.3%), miscellaneous disorders (26, 15.8%), neoplasia plus a second disease
      (13, 7.9%), endocrine diseases (8, 4.8%), and multiple diseases (7, 4.2%). In
      dogs with neoplasia, carcinomas (24) and round cell neoplasms (20), especially
      lymphoma and mast cell tumor, were the most frequent tumors. Inflammatory
      disorders consisted of immune-mediated disorders (11), neurologic diseases (8),
      infectious diseases (6), allergic disease (5), orthopedic diseases (4),
      gastrointestinal diseases (4), and miscellaneous conditions (17). Of the 165
      dogs, 73 (44.2%) had received glucocorticoids (55) or vincristine (18) Marked
      (850-969 * 10(3) platelets/MUL) or extreme ( >= 970 * 10(3) platelets/MUL)
      thrombocytosis occurred in 24 (14.5%) dogs; 12 (50.0%) had neoplasia.
      Thromboembolism occurred in 13 (7.9%) dogs. CONCLUSIONS: Thrombocytosis in dogs
      occurred most frequently secondary to neoplastic and inflammatory diseases and
      was commonly associated with glucocorticoid and vincristine administration.
      Thromboembolic complications occurred in a small number of patients. Marked or
      extreme thrombocytosis was more likely to occur with neoplasia than with other
      conditions.

PMID- 22390567
TI  - Variation in ano-genital distance in spontaneously cycling female mice.
AB  - A recently observed developmental instability of the ano-genital distance (AGD)
      in female mice indicates that natural prenatal androgens do not have such a
      robust effect on female genital morphology as has been generally assumed. Part of
      this instability might be caused by oestrous cyclicity. To check this assumption,
      we examined the effect of the stage of the oestrous cycle on the AGD in adult (61
      75 days old) female mice. Consistent with our assumption, the female AGD (1)
      varied during the oestrous cycle (p < 0.05), indicating thus rapid changes in
      morphology of female external genitalia, and (2) showed good repeatability
      (>0.66) in each stage of the oestrous cycle, suggesting that female genital
      morphology systematically varied within the oestrous cycle. Therefore, the stage
      of the oestrous cycle should be considered when assessing prenatal
      masculinization in adult female mice.

PMID- 22390568
TI  - Preservation of integrity and activity of Haberlea rhodopensis photosynthetic
      apparatus during prolonged light deprivation.
AB  - The effect of prolonged light deprivation on ultrastructure, pigment composition
      and functions of photosynthetic apparatus of the resurrection plant Haberlea
      rhodopensis Friv. (Gesneriaceae) was studied. For this purpose, intact plants
      were kept in darkness for up to 6 months. Haberlea rhodopensis demonstrated
      extraordinary ability to preserve its photosynthetic machinery intact despite
      complete absence of light. During the first 4 weeks of light deprivation, we
      observed preservation of pigment content, chloroplast ultrastructure and a
      decrease in the rate of CO(2)  assimilation. The signs of dark-induced senescence
      were observed only after the fourth week. This phase was characterized by
      decrease of pigment content, partial disintegration of chloroplast ultrastructure
      and by the development of photosystem II down regulation that includes the
      increases in non-photochemical fluorescence quenching, qN. In comparison with
      other plants like common bean and Arabidopsis, the processes of dark-induced
      senescence were very slow and the plants still can recover even after 6 months of
      light deprivation. We think these findings can open new opportunities for
      studying not only dark-induced senescence but also to investigate mechanisms
      determining tolerance to multiple stresses affecting integrity of photosynthetic
      apparatus.

PMID- 22390569
TI  - Acyl and silyl group effects in reactivity-based one-pot glycosylation: synthesis
      of embryonic stem cell surface carbohydrates Lc4 and IV(2)Fuc-Lc4.
AB  - Relative reactivity evaluations showed the graded arming of toluenyl
      thioglucosides by variously positioned silyl groups but not by their acyl
      counterparts. These findings were applied in reactivity-based one-pot assembly of
      linker-attached Lc(4) and IV(2)Fuc-Lc(4), which are components of human embryonic
      stem cell surface. The sugar-galectin-1 binding was also examined.

PMID- 22390570
TI  - Development and design of a multidisciplinary training program for outpatient
      children and adolescents with psoriasis and their parents.
AB  - INTRODUCTION: To describe and illustrate in a case-study design the development
      and design of a multidisciplinary training program for outpatient children and
      adolescents with psoriasis and their parents. METHODS: For the development of the
      program, a steering group was assembled, systematic semi-structured interviews
      were held and the literature was reviewed. RESULTS: Aim of the training program
      was to strengthen patients and their parents in coping with and diminishing
      psoriasis-related problems in an outpatient setting. The program included
      treatment modules of medical information and skin care, itch and scratch
      problems, psychological issues in coping with the psoriasis, sleep hygiene and
      relapse prevention. Descriptive results in the case patient showed improvement of
      all outcome variables in the expected direction. CONCLUSION: This is the first
      multidisciplinary training program for outpatient children and adolescents with
      psoriasis and their parents. It aims at improving coping skills and self
      management and could be a promising addition to regular treatment.

PMID- 22390571
TI  - Detection of clinical and subclinical tubulo-interstitial inflammation by the
      urinary CXCL10 chemokine in a real-life setting.
AB  - Urinary CXCL10 is a promising noninvasive biomarker for tubulo-interstitial
      allograft inflammation, but its diagnostic characteristics have not been assessed
      in a real-life setting. We investigated urinary CXCL10 in 213 consecutive renal
      allograft recipients having 362 surveillance biopsies at 3/6 months and 80
      indication biopsies within the first year posttransplant. Allograft histology
      results were classified as (i) acute Banff score zero, (ii) interstitial
      infiltrates only, (iii) tubulitis t1, (iv) tubulitis t2-3 and (v) isolated
      vascular compartment inflammation. For clinical and subclinical pathologies,
      urinary CXCL10 correlated well with the extent of tubulo-interstitial
      inflammation. To determine diagnostic characteristics of urinary CXCL10,
      histological groups were separated into two categories: no relevant inflammation
      (i.e. acute Banff score zero and interstitial infiltrates only) versus all other
      pathologies (i.e. tubulitis t1-3 and isolated vascular compartment inflammation).
      For subclinical pathologies, AUC was 0.69 (sensitivity 61%, specificity 72%); for
      clinical pathologies, AUC was 0.74 (sensitivity 63%, specificity 80%). A urinary
      CXCL10-guided biopsy strategy would have reduced performance of surveillance and
      indication biopsies by 61% and 64%, respectively. Missed (sub)clinical
      pathologies were mostly tubulitis t1 and isolated vascular compartment lesions.
      In real life, urinary CXCL10 had clinically useful diagnostic properties making
      it a candidate biomarker to guide allograft biopsies.

PMID- 22390572
TI  - Intermittent flushing with heparin versus saline for maintenance of peripheral
      intravenous catheters in a medical department: a pragmatic cluster-randomized
      controlled study.
AB  - BACKGROUND: Three meta-analyses conducted in the 1990s concluded that the effect
      of intermittent flushing with heparin at low concentration (10 U/mL) was
      equivalent to that of 0.9% sodium chloride flushes in preventing occlusion or
      superficial phlebitis. No firm conclusion was reached on the safety and efficacy
      of heparin concentrations of 100 U/mL used as an intermittent flush. PURPOSE: To
      determine whether flushing peripheral intravenous catheters with 3 mL of a 100 U
      heparin/mL solution instead of saline improves the outcome of infusion devices.
      METHODS: Cluster-randomized, controlled, two-arm, open trial, conducted in a
      research and teaching hospital in Northern Italy, involving 214 medical patients
      without contraindications to heparin: 107 randomly allocated to heparin and 107
      to saline flushes (control group). Main outcome measure was catheter occlusion
      and catheter-related phlebitis. RESULTS: Patients with either phlebitis or
      occlusion were 45 (42.1%) in the heparin group and 68 (63.6%) in the saline group
      (OR 0.41; 95% CI 0.24-0.72; p= 0.002); patients with occlusion alone were 23
      (21.5%) and 47 (43.9%), respectively (p= 0.03); patients with phlebitis alone
      were 28 (26.2%) and 56 (52.6%) respectively (p= <0.001). Similar results were
      obtained when the analysis was based on catheters. No heparin severe side effects
      were identified. LIMITATIONS: Lack of blinding, patient selection, cluster
      randomization of periods of treatment. CONCLUSIONS: Heparin 100 U/mL in the
      maintenance of peripheral venous catheters was more effective than saline
      solution, in that it reduced the number of catheter-related phlebitis/occlusions
      and the number of catheters per patient, with potential advantages to both
      patients and the health system. It also appeared safe. However, subjects with
      platelet or coagulation defects were excluded, and, therefore, caution should be
      used when prescribing this type of catheter maintenance to patients at risk of
      bleeding.

PMID- 22390573
TI  - Replacing gasoline with corn ethanol results in significant environmental problem
      shifting.
AB  - Previous studies on the life-cycle environmental impacts of corn ethanol and
      gasoline focused almost exclusively on energy balance and greenhouse gas (GHG)
      emissions and largely overlooked the influence of regional differences in
      agricultural practices. This study compares the environmental impact of gasoline
      and E85 taking into consideration 12 different environmental impacts and regional
      differences among 19 corn-growing states. Results show that E85 does not
      outperform gasoline when a wide spectrum of impacts is considered. If the impacts
      are aggregated using weights developed by the National Institute of Standards and
      Technology (NIST), overall, E85 generates approximately 6% to 108% (23% on
      average) greater impact compared with gasoline, depending on where corn is
      produced, primarily because corn production induces significant eutrophication
      impacts and requires intensive irrigation. If GHG emissions from the indirect
      land use changes are considered, the differences increase to between 16% and 118%
      (33% on average). Our study indicates that replacing gasoline with corn ethanol
      may only result in shifting the net environmental impacts primarily toward
      increased eutrophication and greater water scarcity. These results suggest that
      the environmental criteria used in the Energy Independence and Security Act
      (EISA) be re-evaluated to include additional categories of environmental impact
      beyond GHG emissions.

PMID- 22390574
TI  - The infectious hypodermal and haematopoietic necrosis virus: a brief review of
      what we do and do not know.
AB  - Given its high prevalence, its wide distribution and its remarkable capacity to
      cause severe mortality in shrimp, the infectious hypodermal and haematopoietic
      necrosis virus (IHHNV) may deserve far more attention than it has received, as it
      remains considered as one of the most serious problems plaguing the global shrimp
      farming industry. Furthermore, its real measurable impact over wild shrimp
      populations remains unknown. Undeniably, the progress that we have reached today
      on the knowledge of its geographical distribution, clinical signs, genetic
      diversity, transmission and virulence may help to identify and understand
      important aspects of its biology and pathogenesis. However, the information
      regarding the molecular events that occur during the infection process is scarce.
      Thus, it may not be surprising to find that there are no therapeutic options
      available for the prophylaxis or treatments to reduce the deleterious impact of
      this viral pathogen to date. The aim of this review is to integrate and discuss
      the current state of knowledge concerning several aspects of the biology of IHHNV
      and to highlight potential future directions for this area of research.

PMID- 22390575
TI  - Pathological, immunological and molecular diagnosis of rabies in clinically
      suspected animals of different species using four detection techniques in Jordan.
AB  - A total of 29 brain tissue samples (BTS) were examined for rabies infection by
      different diagnostic techniques. None of the examined brain tissues were
      presented as a whole intact brain. Twenty-seven brain tissue samples from various
      animal species - dog (13 cases), cat (one case), fox (one case), pig (one case),
      cow (three cases), sheep (two cases), goat (one case), camel (one case), horse
      (one case) and donkey (three cases) - were provided by the Vaccine and Sera
      Department/Al-Bashir Central Hospital in Amman/Jordan from July 2009 up to May
      2010. All these samples were frozen at -20 degrees C, for a period of time and
      then fixed in 10% formalin after being tested for rabies virus by fluorescence
      antibody test (FAT). The results showed that 21 (77.77%) of 27 BTS were positive
      for rabies by FAT. Seventeen samples (58.62%) of 29 were positive by
      histopathology, 2 (6.90%) were positive by histopathology, immunohistochemistry
      (IHC) and of those which were fixed for 24h only, and 21 (72.42%) were positive
      using RT-PCR assay. Five of 29 BTS had no pathological lesions, 17 had Negri
      bodies and the remaining had non-suppurative encephalitis and necrosis. Thirteen
      BTS that were diagnosed positive by FAT were also positive by RT-PCR and
      histopathology, but negative by IHC. Four BTS that were positive by FAT were
      negative by histopathology, IHC and RT-PCR. Also, 3 BTS (cases 19, 22, and 25)
      that were negative by FAT were positive by RT-PCR and negative by IHC. One of
      these was negative, while two were positive by histopathology. Therefore,
      definitive diagnosis of rabies under these conditions in Jordan needs one or more
      other diagnostic tests in addition to FAT. Also, freezing and prolonged formalin
      fixation of BTS is not suitable for the detection of rabies virus antigen using
      IHC.

PMID- 22390576
TI  - Increased sensitivity for detecting malaria parasites in human umbilical cord
      blood using scaled-up DNA preparation.
AB  - BACKGROUND: All mothers donating umbilical cord blood units to the NHS cord blood
      bank undergo an assessment for the likelihood of prior exposure to malaria
      infection. Those deemed at risk due to a history of travel to, or residence in,
      malaria endemic regions are screened serologically to detect anti-malaria
      antibodies. A positive result excludes the use of the cord blood for transplant
      therapy unless a risk assessment can ensure that malaria transmission is
      extremely unlikely. This paper details the screening of cord blood units from
      malaria serology positive mothers to detect malaria parasite DNA using a highly
      sensitive nested PCR. METHODS: Uninfected blood from a healthy volunteer was
      spiked with known quantities of malaria parasites and 5 millilitre and 200
      microlitre aliquots were subjected to DNA extraction using QIAamp DNA maxi and
      DNA mini kits respectively. Nested PCR, to detect malarial SSU rRNA sequences,
      was performed on the purified DNA samples to determine the limit of detection for
      this assay with both extraction methodologies. Following assay validation, 54
      cord blood units donated by mothers who were positive for anti-malaria antibodies
      were screened by this approach. RESULTS: When DNA was purified from 5 millilitres
      of blood it was possible to routinely detect as few as 50 malaria parasites per
      millilitre using nested PCR. This equates to a significant increase in the
      sensitivity of the current gold standard nucleic acid amplification technique
      used to detect malaria parasites (routinely performed from > 200 microlitre
      volumes of blood). None of the 54 donated cord blood units from serology positive
      mothers tested positive for malaria parasites using this scaled up DNA
      preparation method. CONCLUSION: Serological testing for malaria parasites may be
      overly conservative, leading to unnecessary rejection of cord blood donations
      that lack malaria parasites and which are, therefore, safe for use in stem cell
      therapy.

PMID- 22390578
TI  - Preventing suicide by preventing lethal injury: the need to act on what we
      already know.

PMID- 22390577
TI  - Predictors of new atherosclerotic carotid plaque development in patients with
      rheumatoid arthritis: a longitudinal study.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is associated with increased
      cardiovascular morbidity and mortality attributed to both classical risk factors
      and chronic inflammation. We assessed longitudinally the factors associated with
      new carotid plaques in nondiabetic RA patients and apparently healthy
      individuals. METHODS: In our present prospective observational study, carotid
      plaques were identified by ultrasonography at baseline and follow-up end,
      separated by an average of 3.6 +/- 0.2 years, in 64 patients (mean age 59.2 +/-
      12.0 and disease duration at baseline 7.8 +/- 6.2 years, 83% women, clinical and
      laboratory evaluation every 3 to 6 months). In a substudy, 35 of the patients
      were matched 1:1 for traditional cardiovascular risk factors with 'healthy'
      controls and were studied in parallel. RESULTS: New atherosclerotic plaques
      formed in 30% of patients (first plaque in 9%) who were significantly older than
      the remaining patients. Tobacco use, blood pressure, body mass index, average
      cumulative low-density lipoprotein, high-sensitivity C-reactive protein,
      erythrocyte sedimentation rate level, RA stage, functional class, disease
      duration and treatment modalities during follow-up did not differ significantly
      between subgroups after application of the Bonferroni correction. RA was in
      clinical remission, on average, for approximately 70% of the follow-up time and
      was not different between subgroups. Multivariate analysis including all the
      above parameters revealed that age (P = 0.006), smoking (P = 0.009) and duration
      of low-dose corticosteroid use (P = 0.016) associated independently with new
      plaque formation. RA patients displayed similar numbers of newly formed carotid
      plaques to the tightly matched for traditional cardiovascular risk factors
      'healthy' controls, although more patients than controls had carotid plaques at
      baseline. CONCLUSIONS: Formation of new atherosclerotic plaques in this small
      cohort of patients with well-controlled RA depended mainly on traditional
      cardiovascular risk factors and corticosteroid use, whereas an adverse effect of
      residual systemic inflammation was not readily detectable.

PMID- 22390579
TI  - Surveillance of suicide and suicide attempts among veterans: addressing a
      national imperative.

PMID- 22390580
TI  - Suicide prevention is a winnable battle.

PMID- 22390581
TI  - Precedence for integration of clinical services in public health initiatives.

PMID- 22390582
TI  - Suicide among veterans in 16 states, 2005 to 2008: comparisons between utilizers
      and nonutilizers of Veterans Health Administration (VHA) services based on data
      from the National Death Index, the National Violent Death Reporting System, and
      VHA administrative records.
AB  - OBJECTIVES: We sought to compare suicide rates among veterans utilizing Veterans
      Health Administration (VHA) services versus those who did not. METHODS: Suicide
      rates from 2005 to 2008 were estimated for veterans in the 16 states that fully
      participated in the National Violent Death Reporting System (NVDRS), using data
      from the National Death Index, NVDRS, and VHA records. RESULTS: Between 2005 and
      2008, veteran suicide rates differed by age and VHA utilization status. Among men
      aged 30 years and older, suicide rates were consistently higher among VHA
      utilizers. However, among men younger than 30 years, rates declined significantly
      among VHA utilizers while increasing among nonutilizers. Over these years, an
      increasing proportion of male veterans younger than 30 years received VHA
      services, and these individuals had a rising prevalence of diagnosed mental
      health conditions. CONCLUSIONS: The higher rates of suicide for utilizers of VHA
      among veteran men aged 30 and older were consistent with previous reports about
      which veterans utilize VHA services. The increasing rates of mental health
      conditions in utilizers younger than 30 years suggested that the decreasing
      relative rates in this group were related to the care provided, rather than to
      selective enrollment of those at lower risk for suicide.

PMID- 22390583
TI  - Suicide among patients in the Veterans Affairs health system: rural-urban
      differences in rates, risks, and methods.
AB  - OBJECTIVES: Using national patient cohorts, we assessed rural-urban differences
      in suicide rates, risks, and methods in veterans. METHODS: We identified all
      Department of Veterans Affairs (VA) patients in fiscal years 2003 to 2004 (FY03
      04) alive at the start of FY04 (n = 5,447,257) and all patients in FY06-07 alive
      at the start of FY07 (n = 5,709,077). Mortality (FY04-05 and FY07-08) was
      assessed from National Death Index searches. Census criteria defined rurality. We
      used proportional hazards regressions to calculate rural-urban differences in
      risks, controlling for age, gender, psychiatric diagnoses, VA mental health
      services accessibility, and regional administrative network. Suicide method was
      categorized as firearms, poisoning, strangulation, or other. RESULTS: Rural
      patients had higher suicide rates (38.8 vs 31.4/100,000 person-years in FY04-05;
      39.6 vs 32.4/100,000 in FY07-08). Rural residence was associated with greater
      suicide risks (20% greater, FY04-05; 22% greater, FY07-08). Firearm deaths were
      more common in rural suicides (76.8% vs 61.5% in FY07-08). CONCLUSIONS: Rural
      residence is a suicide risk factor, even after controlling for mental health
      accessibility. Public health and health system suicide prevention should address
      risks in rural areas.

PMID- 22390584
TI  - The role of pain, functioning, and mental health in suicidality among Veterans
      Affairs primary care patients.
AB  - OBJECTIVES: We examined suicidality, pain, functioning, and psychiatric disorders
      among veterans in primary care by using both self-report and clinical measures of
      pain and mental health to determine correlates that might be clinically useful in
      primary care settings. METHODS: Data were from 884 Veterans Affairs patients
      enrolled in a regional 4-site cross-sectional study. Patients were administered
      measures that assessed functioning (including pain) and psychiatric disorders.
      Data were merged with medical records for clinical pain indicators. RESULTS:
      Overall, 9.1% (74 of 816) of patients indicated suicidal ideation, with those who
      were middle-aged, unemployed because of disability, had less than college
      education, and served in a warzone most likely to consider suicidality. Suicidal
      patients had worse functioning (measured by the Short Form-36) than did
      nonsuicidal patients in every domain, including bodily pain, and were more likely
      to meet criteria for a psychiatric diagnosis. However, when pain and mental
      health were jointly considered, only mental health (both psychiatric diagnosis
      and mental health functioning) was related to suicidality. CONCLUSIONS: Although
      providers should be alert to the possibility of suicidality in patients with
      pain, they should be vigilant when patients have a psychiatric disorder or poor
      mental health.

PMID- 22390585
TI  - Facilitating treatment engagement during high-risk transition periods: a
      potential suicide prevention strategy.

PMID- 22390586
TI  - Differences between veteran suicides with and without psychiatric symptoms.
AB  - OBJECTIVES: Our objective was to examine all suicides (n = 423) in 2 geographic
      areas of the Veterans Health Administration (VHA) over a 7-year period and to
      perform detailed chart reviews on the subsample that had a VHA visit in the last
      year of life (n = 381). METHODS: Within this sample, we compared a group with 1
      or more documented psychiatric symptoms (68.5%) to a group with no such symptoms
      (31.5%). The groups were compared on suicidal thoughts and behaviors, somatic
      symptoms, and stressors using the chi(2) test and on time to death after the last
      visit using survival analyses. RESULTS: Veterans with documented psychiatric
      symptoms were more likely to receive a suicide risk assessment, and have suicidal
      ideation and a suicide plan, sleep problems, pain, and several stressors. These
      veterans were also more likely to die in the 60 days after their last visit.
      CONCLUSIONS: Findings indicated presence of 2 large and distinct groups of
      veterans at risk for suicide in the VHA, underscoring the value of tailored
      prevention strategies, including approaches suitable for those without identified
      psychiatric symptoms.

PMID- 22390587
TI  - Suicide risk and precipitating circumstances among young, middle-aged, and older
      male veterans.
AB  - OBJECTIVES: The purpose of this study was to evaluate the risk of suicide among
      veteran men relative to nonveteran men by age and to examine the prevalence of
      suicide circumstances among male veterans in different age groups (18-34, 35-44,
      45-64, and >= 65 years). METHODS: Data from the National Violent Death Reporting
      System (2003-2008) were used to calculate age-specific suicide rates for veterans
      (n = 8440) and nonveterans (n = 21,668) and to calculate the age-stratified
      mortality ratio for veterans. Multiple logistic regression was used to compare
      health status, stressful life events preceding suicide, and means of death among
      young, middle-aged, and older veterans. RESULTS: Veterans were at higher risk for
      suicide compared with nonveterans in all age groups except the oldest. Mental
      health, substance abuse, and financial and relationship problems were more common
      in younger than in older veteran suicide decedents, whereas health problems were
      more prevalent in the older veterans. Most male veterans used firearms for
      suicide, and nearly all elderly veterans did so. CONCLUSIONS: Our study
      highlighted heightened risk of suicide in male veterans compared with
      nonveterans. Within the veteran population, suicide might be influenced by
      different precipitating factors at various stages of life.

PMID- 22390588
TI  - Suicide incidence and risk factors in an active duty US military population.
AB  - OBJECTIVES: The goal of this study was to investigate and identify risk factors
      for suicide among all active duty members of the US military during 2005 or 2007.
      METHODS: The study used a cross-sectional design and included the entire active
      duty military population. Study sample sizes were 2,064,183 for 2005 and
      1,981,810 for 2007. Logistic regression models were used. RESULTS: Suicide rates
      for all services increased during this period. Mental health diagnoses, mental
      health visits, selective serotonin reuptake inhibitors (SSRIs), sleep
      prescriptions, reduction in rank, enlisted rank, and separation or divorce were
      associated with suicides. Deployments to Operation Enduring Freedom or Operation
      Iraqi Freedom were also associated with elevated odds ratios for all services in
      the 2007 population and for the Army in 2005. CONCLUSIONS: Additional research
      needs to address the increasing rates of suicide in active duty personnel. This
      should include careful evaluation of suicide prevention programs and the possible
      increase in risk associated with SSRIs and other mental health drugs, as well as
      the possible impact of shorter deployments, age, mental health diagnoses, and
      relationship problems.

PMID- 22390589
TI  - Lessons learned from mental health enhancement and suicide prevention activities
      in the Veterans Health Administration.

PMID- 22390590
TI  - Suicidal behavior in a national sample of older homeless veterans.
AB  - OBJECTIVES: We examined self-reported suicidal behavior of older homeless
      veterans to establish frequencies and predictors of recent suicidal behaviors,
      and their impact on transitional housing interventions. METHODS: We analyzed the
      records of a national sample of 10,111 veterans who participated in a transition
      housing program over a 6-year period, ending in 2008. RESULTS: Approximately 12%
      of homeless veterans reported suicidal ideation before program admission; 3%
      reported a suicide attempt in the 30 days before program admission. Older
      homeless veterans exhibiting suicidal behavior had histories of high rates of
      psychiatric disorders and substance abuse. Regression analyses showed that self
      report of depression was the primary correlate of suicidal behavior. Suicidal
      behavior before program entry did not predict intervention outcomes, such as
      program completion, housing outcome, and employment. CONCLUSIONS: Suicidal
      behavior was prevalent in older homeless veterans and was associated with a
      history of psychiatric disorder and substance abuse. Self-reported depression was
      associated with these behaviors at the time of housing intervention. Despite the
      association with poor mental health history, suicidal behavior in older homeless
      veterans did not impact outcomes of transitional housing interventions.

PMID- 22390591
TI  - Veterans and suicide: a reexamination of the National Death Index-linked National
      Health Interview Survey.
AB  - OBJECTIVES: We assessed the risk of suicide among veterans compared with
      nonveterans. METHODS: Cox proportional hazards models estimated the relative risk
      of suicide, by self-reported veteran status, among 500,822 adult male
      participants in the National Death Index (NDI)-linked National Health Interview
      Survey (NHIS), a nationally representative cohort study. RESULTS: A total of 482
      male veterans died by suicide during 1,837,886 person-years of follow-up (76% by
      firearm); 835 male nonveterans died by suicide during 4,438,515 person-years of
      follow-up (62% by firearm). Crude suicide rates for veterans and nonveterans
      were, respectively, 26.2 and 18.8 per 100,000 person-years. The risk of suicide
      was not significantly higher among veterans, compared with nonveterans, after
      adjustment for differences in age, race, and survey year (hazard ratio = 1.11;
      95% confidence interval = 0.96, 1.29). CONCLUSIONS: Consistent with most studies
      of suicide risk among veterans of conflicts before Operation Iraqi
      Freedom/Operation Enduring Freedom, but in contrast to a previous study using the
      NDI-linked NHIS data, we found that male veterans responding to the NHIS were
      modestly, but not significantly, at higher risk for suicide compared with male
      nonveterans.

PMID- 22390592
TI  - Is the rate of suicide among veterans elevated?

PMID- 22390593
TI  - A call to link data to answer pressing questions about suicide risk among
      veterans.

PMID- 22390594
TI  - Estimating the risk of suicide among US veterans: how should we proceed from
      here?

PMID- 22390595
TI  - Addressing the surveillance goal in the National Strategy for Suicide Prevention:
      the Department of Defense Suicide Event Report.
AB  - The US National Strategy for Suicide Prevention (National Strategy) described 11
      goals across multiple areas, including suicide surveillance. Consistent with
      these goals, the Department of Defense (DoD) has engaged aggressively in the area
      of suicide surveillance.  The DoD's population-based surveillance system, the DoD
      Suicide Event Report (DoDSER) collects information on suicides and suicide
      attempts for all branches of the military. Data collected includes suicide event
      details, treatment history, military and psychosocial history, and psychosocial
      stressors at the time of the event.  Lessons learned from the DoDSER program are
      shared to assist other public health professionals working to address the
      National Strategy objectives.

PMID- 22390596
TI  - Implementation and early utilization of a Suicide Hotline for veterans.
AB  - Suicide crisis lines have a respected history as a strategy for reducing deaths
      from suicide and suicidal behaviors. Until recently, however, evidence of the
      effectiveness of these crisis lines has been sparse. Studies published during the
      past decade suggest that crisis lines offer an alternative to populations who may
      not be willing to engage in treatment through traditional mental health settings.
      Given this promising evidence, in 2007, the Department of Veterans Affairs in
      collaboration with the Department of Health and Human Services' Substance Abuse
      and Mental Health Administration implemented a National Suicide Hotline that is
      staffed 24 hours a day, 7 days a week, by Veterans Affairs clinical staff. We
      report here on the implementation of this suicide hotline and our early
      observations of its utilization in a largely male population.

PMID- 22390597
TI  - An emergency department-based brief intervention for veterans at risk for suicide
      (SAFE VET).
AB  - Reducing deaths from veteran suicide is a public health priority for veterans who
      receive their care from the Department of Veterans Affairs (VA) and those who
      receive services in community settings. Emergency departments frequently function
      as the primary or sole point of contact with the health care system for suicidal
      individuals; therefore, they represent an important venue in which to identify
      and treat veterans who are at risk for suicide. We describe the design,
      implementation and initial evaluation of a brief behavioral intervention for
      suicidal veterans seeking care at VA emergency departments. Initial findings of
      the feasibility and acceptability of the intervention suggest it may be
      transferable to diverse VA and non-VA settings, including community emergency
      departments and urgent care centers.

PMID- 22390598
TI  - Prevalence and characteristics of suicide ideation and attempts among active
      military and veteran participants in a national health survey.
AB  - The relationships between military service and suicide are not clear, and
      comparatively little is known about the characteristics and correlates of suicide
      ideation and attempts among those with history of military service. We used data
      from a national health survey to estimate the prevalence and correlates of
      suicidal behaviors among veterans and service members in 2 states. The prevalence
      of suicidal behaviors among Veterans was similar to previous estimates of
      ideation and attempts among adults in the US general population.

PMID- 22390599
TI  - Characteristics of suicides among US army active duty personnel in 17 US states
      from 2005 to 2007.
AB  - Suicides are increasing among active duty US Army soldiers. To help focus
      prevention strategies, we characterized 56 US Army suicides that occurred from
      2005 to 2007 in 17 US states using 2 large-scale surveillance systems. We found
      that intimate partner problems and military-related stress, particularly job
      stress, were common among decedents. Many decedents were also identified as
      having suicidal ideation, a sad or depressed mood, or a recent crisis before
      death. Focusing efforts to prevent these forms of stress might reduce suicides
      among soldiers.

PMID- 22390600
TI  - Suicidal ideation among sexual minority veterans: results from the 2005-2010
      Massachusetts Behavioral Risk Factor Surveillance Survey.
AB  - Suicide is a public health problem disproportionately associated with some
      demographic characteristics (e.g., sexual orientation, veteran status). Analyses
      of the Massachusetts Behavioral Risk Factor Surveillance Survey data revealed
      that more lesbian, gay, and bisexual (i.e., sexual minority) veterans reported
      suicidal ideation compared with heterosexual veterans. Decreased social and
      emotional support contributed to explaining the association between sexual
      minority status and suicidal ideation. More research is needed about suicide risk
      among sexual minority veterans; they might be a population for outreach and
      intervention by the Veterans Health Administration.

PMID- 22390601
TI  - Effect of dwell time on the mental health of US military personnel with multiple
      combat tours.
AB  - OBJECTIVE: We investigated the association of the length of time spent at home
      between deployments, or dwell time, with posttraumatic stress disorder (PTSD) and
      other mental health disorders. METHODS: We included US Marine Corps personnel
      identified from military deployment records who deployed to Operation Iraqi
      Freedom once (n = 49,328) or twice (n = 16,376). New-onset mental health
      diagnoses from military medical databases were included. We calculated the ratio
      of dwell-to-deployment time (DDR) as the length of time between deployments
      divided by the length of the first deployment. RESULTS: Marines with 2
      deployments had higher rates of PTSD than did those with 1 deployment (2.1%
      versus 1.2%; P < .001). A DDR representing longer dwell times at home relative to
      first deployment length was associated with reduced odds of PTSD (odds ratio [OR]
      = 0.47; 95% confidence interval [CI] = 0.32, 0.70), PTSD with other mental health
      disorder (OR = 0.56; 95% CI = 0.33, 0.94), and other mental health disorders (OR
      = 0.62; 95% CI = 0.51, 0.75). CONCLUSIONS: Longer dwell times may reduce
      postdeployment risk of PTSD and other mental health disorders. Future research
      should focus on the role of dwell time in adverse health outcomes.

PMID- 22390603
TI  - Local board of health authority to address obesity.

PMID- 22390604
TI  - Use of the Air Force Post-Deployment Health Reassessment for the identification
      of depression and posttraumatic stress disorder: public health implications for
      suicide prevention.
AB  - OBJECTIVES: Military members are required to complete the Post-Deployment Health
      Assessment on return from deployment and the Post-Deployment Health Reassessment
      (PHDRA) 90 to 180 days later, and we assessed the PDHRA's sensitivity and
      specificity in identifying posttraumatic stress disorder (PTSD) and depression
      after a military deployment among US Air Force personnel. METHODS: We computed
      the PDHRA's sensitivity and specificity for depression and PTSD and developed a
      structural model to suggest possible improvements to it. RESULTS: For depression,
      sensitivity and specificity were 0.704 and 0.651, respectively; for PTSD, they
      were 0.774 and 0.650, respectively. Several variables produced significant direct
      effects on depression and trauma, suggesting that modifications could increase
      its sensitivity and specificity. CONCLUSIONS: The PDHRA was moderately effective
      in identifying airmen with depression and PTSD. It identified behavioral health
      concerns in many airmen who did not develop a diagnostic mental health condition.
      Its low level of specificity may result in reduced barriers to care and increased
      support services, key components of a public health approach to suicide
      prevention, for airmen experiencing subacute levels of distress after deployment,
      which may, in part, account for lower suicide rates among airmen after
      deployment.

PMID- 22390606
TI  - Preventing suicide is a national imperative.

PMID- 22390605
TI  - Mental and physical health status and alcohol and drug use following return from
      deployment to Iraq or Afghanistan.
AB  - OBJECTIVES: We examined (1) mental and physical health symptoms and functioning
      in US veterans within 1 year of returning from deployment, and (2) differences by
      gender, service component (Active, National Guard, other Reserve), service branch
      (Army, Navy, Air Force, Marines), and deployment operation (Operation Enduring
      Freedom/Operation Iraqi Freedom [OEF/OIF]). METHODS: We surveyed a national
      sample of 596 OEF/OIF veterans, oversampling women to make up 50% of the total,
      and National Guard and Reserve components to each make up 25%. Weights were
      applied to account for stratification and nonresponse bias. RESULTS: Mental
      health functioning was significantly worse compared with the general population;
      13.9% screened positive for probable posttraumatic stress disorder, 39% for
      probable alcohol abuse, and 3% for probable drug abuse. Men reported more alcohol
      and drug use than did women, but there were no gender differences in
      posttraumatic stress disorder or other mental health domains. OIF veterans
      reported more depression or functioning problems and alcohol and drug use than
      did OEF veterans. Army and Marine veterans reported worse mental and physical
      health than did Air Force or Navy veterans. CONCLUSIONS: Continuing
      identification of veterans at risk for mental health and substance use problems
      is important for evidence-based interventions intended to increase resilience and
      enhance treatment.

PMID- 22390607
TI  - Reduced mortality among Department of Veterans Affairs patients with
      schizophrenia or bipolar disorder lost to follow-up and engaged in active
      outreach to return for care.
AB  - OBJECTIVES: We determined whether contacting Department of Veterans Affairs (VA)
      patients with schizophrenia or bipolar disorders (serious mental illness [SMI])
      who had dropped out of care for prolonged periods resulted in reengagement with
      VA services and decreased mortality. METHODS: We developed a list of patients
      with SMI who were last treated in fiscal years 2005 to 2006, and were lost to
      follow-up care for at least 1 year. VA medical centers used our list to contact
      patients and schedule appointments. Additional VA administrative data on patient
      utilization and mortality through May 2009 were analyzed. RESULTS: About 72%
      (2375 of 3306) of the patients who VA staff attempted to contact returned for VA
      care. The mortality rate of returning patients was significantly lower than that
      for patients not returning (0.5% vs 3.9%; adjusted odds ratio = 5.8; P < .001),
      after demographic and clinical factors were controlled. CONCLUSIONS: The
      mortality rate for returning patients with SMI was almost 6 times less than for
      those who did not return for medical care. Proactive outreach might result in
      patients returning to care and should be implemented to reengage this vulnerable
      group.

PMID- 22390608
TI  - Suicide prevention for veterans and active duty personnel.

PMID- 22390609
TI  - Effects of Iraq/Afghanistan deployments on major depression and substance use
      disorder: analysis of active duty personnel in the US military.
AB  - OBJECTIVES: Our objective was to analyze the association between deployment
      characteristics and diagnostic rates for major depression and substance use
      disorder among active duty personnel. METHODS: Using active duty personnel
      serving between 2001 and 2006 (n = 678,382) and deployment information from the
      Contingent Tracking System, we identified individuals diagnosed with substance
      use disorders and major depression from TRICARE health records. We performed
      logistic regression analysis to assess the effect of deployment location and
      length on these diagnostic rates. RESULTS: Increased odds of diagnosis with both
      conditions were associated with deployment to Iraq or Afghanistan compared with
      nondeployed personnel and with Army and Marine Corps personnel compared with Navy
      and Air Force personnel. Increases in the likelihood of either diagnosis with
      deployment length were only observed among Army personnel. CONCLUSIONS: There
      were increased substance use disorders and major depression across services
      associated with combat conditions. It would be important to assess whether the
      public health system has adequate resources to handle the increasing need of
      mental health services in this population.

PMID- 22390610
TI  - Patterns of treatment utilization before suicide among male veterans with
      substance use disorders.
AB  - OBJECTIVES: We sought to describe the extent and nature of contact with the
      health care system before suicide among veterans with substance use disorders
      (SUDs). METHODS: We examined all male Veterans Health Administration patients who
      died by suicide between October 1, 1999, and September 30, 2007, and who had a
      documented SUD diagnosis during the 2 years before death (n = 3132). RESULTS:
      Over half (55.5%; n = 1740) of the male patients were seen during the month
      before suicide, and 25.4% (n = 796) were seen during the week before suicide. In
      examining those with a medical visit in the year before suicide (n = 2964), most
      of the last visits before suicide (56.6%; n = 1679) were in a general medical
      setting, 32.8% (n = 973) were in a specialty mental health setting, and 10.5% (n
      = 312) were in SUD treatment. CONCLUSIONS: Men with SUDs who died from suicide
      were frequently seen in the month before their death. Most were last seen in
      general medical settings, although a substantial minority of those with SUDs was
      seen in specialty mental health settings.

PMID- 22390611
TI  - Sleep disturbance preceding suicide among veterans.
AB  - OBJECTIVES: We examined the role of sleep disturbance in time to suicide since
      the last treatment visit among veterans receiving Veterans Health Administration
      (VHA) services. METHODS: Among 423 veteran suicide decedents from 2 geographic
      areas, systematic chart reviews were conducted on the 381 (90.1%) who had a VHA
      visit in the last year of life. Veteran suicides with a documented sleep
      disturbance (45.4%) were compared with those without sleep disturbance (54.6%) on
      time to death since their last VHA visit using an accelerated failure time model.
      RESULTS: Veterans with sleep disturbance died sooner after their last visit than
      did those without sleep disturbance, after we adjusted for the presence of mental
      health or substance use symptoms, age, and region. CONCLUSIONS: Findings
      indicated that sleep disturbance was associated with time to suicide in this
      sample of veterans who died by suicide. The findings had implications for using
      the presence of sleep disturbance to detect near-term risk for suicide and
      suggested that sleep disturbance might provide an important intervention target
      for a subgroup of at-risk veterans.

PMID- 22390612
TI  - Suicide mortality among patients treated by the Veterans Health Administration
      from 2000 to 2007.
AB  - OBJECTIVES: We sought to examine rates of suicide among individuals receiving
      health care services in Veterans Health Administration (VHA) facilities over an 8
      year period. METHODS: We included annual cohorts of all individuals who received
      VHA health care services from fiscal year (FY) 2000 through FY 2007 (October 1,
      1999-September 30, 2007; N = 8,855,655). Vital status and cause of death were
      obtained from the National Death Index. RESULTS: Suicide was more common among
      VHA patients than members of the general US population. The overall rates of
      suicide among VHA patients decreased slightly but significantly from 2000 to 2007
      (P < .001). Male veterans between the ages of 30 and 64 years were at the highest
      risk of suicide. CONCLUSIONS: VHA health care system patients are at elevated
      risk for suicide and are appropriate for suicide reduction services, although the
      rate of suicide has decreased in recent years for this group. Comprehensive
      approaches to suicide prevention in the VHA focus not only on recent returnees
      from Iraq and Afghanistan but also on middle-aged and older Veterans.

PMID- 22390613
TI  - Anatomical placement of the human eyeball in the orbit--validation using CT scans
      of living adults and prediction for facial approximation.
AB  - Accuracy of forensic facial approximation and superimposition techniques relies
      on the knowledge of anatomical correlations between soft and hard tissues. Recent
      studies by Stephan and collaborators (6,8,10) reviewed traditional guidelines
      leading to a wrong placement of the eyeball in the orbit. As those statements are
      based on a small cadaver sample, we propose a validation of these findings on a
      large database (n = 375) of living people. Computed tomography scans of known age
      and sex subjects were used to collect landmarks on three-dimensional surfaces and
      DICOM with TIVMI. Results confirmed a more superior and lateral position of the
      eyeball relatively to the orbital rims. Orbital height and breadth were used to
      compute regression formulae and proportional placement using percentages to find
      the most probable position of the eyeball in the orbit. A size-related sexual
      dimorphism was present but did not impact on the prediction accuracy.

PMID- 22390614
TI  - Electron energy loss spectra and overestimation of inelastic mean free paths in
      many-pole models.
AB  - We investigate established theoretical approaches for the determination of
      electron energy loss spectra (EELS) and inelastic mean free paths (IMFPs) in
      solids. In particular, we investigate effects of alternate descriptions of the
      many plasmon resonances that define the energy loss function (ELF), and the
      contribution of lifetime broadening in these resonances to the IMFP. We find that
      despite previously claimed agreement between approaches, approximations of
      different models consistently conspire to underestimate electron scattering for
      energies below 100 eV, leading to significant overestimates of the IMFP in this
      regime.

PMID- 22390615
TI  - Case of annular-shaped giant basal cell carcinoma.

PMID- 22390616
TI  - Heterogeneity of multiple-pore membranes investigated with ion conductance
      microscopy.
AB  - Heterogeneous conductance of individual pores on a porous membrane was studied
      with a four-electrode scanning ion conductance microscope (SICM). Application of
      a potential difference across the membrane resulted in migration of ions through
      nanopores, where subsequent conductance changes were measured by a nanopipet
      positioned above the nanopore as a change in pipet current. Current responses of
      single-pore membranes and individual pores within a multipore membrane were
      examined and demonstrated variations in ion current rectification (ICR) ratios
      due to the small differences in pore geometries.

PMID- 22390617
TI  - Daptomycin failure in a neutropenic leukemia patient with Staphylococcus aureus
      meningitis.

PMID- 22390618
TI  - Second-order-like cluster-monomer transition within magnetic fluids and its
      impact upon the magnetic susceptibility.
AB  - The low-field (below 5 Oe) ac and dc magnetic response of a magnetic fluid [MF]
      sample in the range of 305 to 360 K and 410 to 455 K was experimentally and
      theoretically investigated. We found a systematic deviation of Curie's law, which
      predicts a linear temperature dependence of inverse initial susceptibility in the
      range of our investigation. This finding, as we hypothesized, is due to the onset
      of a second-order-like cluster-to-monomer transition with a critical exponent
      which is equal to 0.50. The susceptibility data were well fitted by a modified
      Langevin function, in which cluster dissociation into monomers, at the critical
      temperature [T*], was included. In the ac experiments, we found that T* was
      reducing from 381.8 to 380.4 K as the frequency of the applied field increases
      from 123 to 173 Hz. In addition, our ac experiments confirm that only monomers
      respond for the magnetic behavior of the MF sample above T*. Furthermore, our
      Monte Carlo simulation and analytical results support the hypothesis of a thermal
      assisted dissociation of chain-like structures.PACS: 75.75.-C; 75.30.Kz;
      75.30.Cr.

PMID- 22390619
TI  - Radial-arm-maze behavior of the red-footed tortoise (Geochelone carbonaria).
AB  - The radial-arm maze is an established method for testing an animal's spatial win
      shift behavior. Research on mammals, birds, and fish has shown that the mastery
      of this task is commonly mediated, to different degrees, by two types of
      strategy: those based on external cues and those based on response stereotypy. In
      the present study we trained four red-footed tortoises (Geochelone carbonaria) to
      navigate an eight-arm radial maze while providing different levels of access to
      visual room cues. The results indicate that response stereotypy is the more
      prevalent mechanism in these tortoises, although navigation based on landmarks
      can also occur if learned initially. The findings suggest that tortoise spatial
      navigation may be more similar to that observed in mammals and birds than
      previously thought.

PMID- 22390620
TI  - Evidence for individual differences in regulatory focus in rats, Rattus
      norvegicus.
AB  - Regulatory focus (Higgins, 1997) builds on the classic approach-avoidance
      distinction by identifying two important approach orientations: the promotion
      focus (approaching gains and attainment) and the prevention focus (approaching
      nonlosses and safety). Though individual differences in regulatory focus have
      been widely studied in human psychology, it is unknown if such differences exist
      in other species. To explore this possibility, we designed a series of tests for
      laboratory rats, paralleling human regulatory focus research on risk taking. In
      home-cage tests, rats (N = 23) were given an opportunity to prevent a loss by
      burying a noxious novel object. In solitary tests in a novel enclosure, the same
      rats had the opportunity to pursue gains (food rewards) and/or safety (darkness).
      Rats demonstrated stable individual differences on both tests (p's < .001).
      Complementing the human research, duration of time spent with the noxious novel
      object was predicted by an individual's tendency to pursue safety (p < .01) and
      not by the tendency to pursue gains (p > .8). Some aspects of these results were
      compatible with alternative approaches, such as the bold-shy axis and "if-then"
      personality profiles (Mischel & Shoda, 1995). Regulatory focus theory, however,
      was uniquely able to predict the overall pattern, which may be an indication that
      it could contribute to future research in animal personality, motivation, and
      welfare.

PMID- 22390622
TI  - Use of slope and feature cues in pigeon (Columba livia) goal-searching behavior.
AB  - Terrain slope provides a directional frame of reference for reorientation and
      navigation, similar to cardinal directions. Previous studies have shown that, in
      a goal location task, slope is a very salient cue and that pigeons tend to rely
      on it even if it is not the most informative cue. Such a strong dependence on one
      type of information, when there are more effective predictors of reward, is a key
      premise for a modular view of information processing. Here we tested the
      provocative hypothesis of a "slope module" for reorientation in slanted
      environments. Pigeons had to solve a goal location task using slope or another,
      theoretically salient cue: a beacon feature. Overall, searching behavior was
      controlled almost equally by the two cues. The fact that, for the first time,
      slope failed to capture most of the associative strength allows us to reject a
      strong modularity view and suggests instead that there is competition between
      cues based on salience. As an interesting additional finding, the reliance on
      slope and the feature was affected by training location (uphill vs. downhill),
      suggesting the possibility of a modulatory role of effort on the cue-weighting
      mechanism of reorientation.

PMID- 22390621
TI  - The composite face effect in chimpanzees (Pan troglodytes) and rhesus monkeys
      (Macaca mulatta).
AB  - The accurate recognition of individuals is a cornerstone of social exchange in
      primates. Current approaches to the study of individual recognition, however, are
      focused on human performance and only occasionally reference comparative research
      for support. A number of studies have suggested that humans can easily recognize
      thousands of individual faces and that this perceptual expertise is supported by
      holistic processing, a phenomenon best demonstrated by the composite face effect
      (CFE). Recent advances have indicated that the CFE in humans is robust to changes
      in contrast polarity (positive or negative). Here we apply a two alternative
      forced choice match-to-sample paradigm across two species of nonhuman primate,
      chimpanzees (Pan troglodyte) and rhesus monkeys (Macaca mulatta). We find strong
      evidence that chimpanzees and rhesus monkeys experience interference from
      holistic processing in the positive contrast condition. While there is some
      indication that the chimpanzees experienced a CFE in the negative contrast
      condition, there was no evidence of a CFE in the corresponding rhesus monkey
      data. These results suggest that, while holistic processing is a general
      mechanism, rhesus monkeys are more sensitive to contrast-polarity than humans.

PMID- 22390623
TI  - The effect of body orientation on judgments of human visual attention in western
      lowland gorillas (Gorilla gorilla gorilla).
AB  - The ability to appreciate the attentional states of others is an important
      element used in discerning the presence of Theory of Mind in an individual.
      Whether primates are able to recognize attention, and further, use such
      information to predict behavior, remains contentious. In this study, six western
      lowland gorillas (Gorilla gorilla gorilla) were tested under different conditions
      that aimed to investigate not only their understanding of what a human
      experimenter sees, but also what information they use to make these judgments. In
      all experiments the gorillas selected between two human experimenters, one who
      could see them and one who could not. In Experiment 1 the gorillas' performance
      was significantly above chance in conditions where they judged body orientation,
      head orientation, and eyes. Experiment 2 showed that the gorillas' initial
      judgments of attention may be based on body orientation rather than facial cues.
      Experiment 3 demonstrated that the gorillas were better able to utilize facial
      cues in some conditions, when these cues were paired with a more neutral body
      orientation. These findings suggest that the gorillas are using a hierarchical
      approach to determining visual attention, by making an immediate decision based
      on the most salient cue-body orientation. However, when body orientation is more
      ambiguous their ability to judge the less prominent cues of the face and eyes
      does improve.

PMID- 22390624
TI  - Community-acquired pneumonia in immunocompromised older patients: incidence,
      causative organisms and outcome.
AB  - The number of elderly patients in the community with immunosuppressive conditions
      has increased progressively over recent decades. We sought to determine the
      incidence, causative organisms and outcome of community-acquired pneumonia (CAP)
      occurring in immunocompromised older patients. We prospectively compared cases of
      CAP in immunocompromised and non-immunocompromised patients admitted to five
      public hospitals in three Spanish regions. Of 320 cases studied, 115 (36%)
      occurred in immunocompromised patients, including: solid or hematological
      malignancy (97), corticosteroids or other immunosuppressive drugs (44), solid
      organ or stem cell transplant (five), and other conditions (eight). The etiology
      was established in 44% of immunocompromised patients vs. 32% of non
      immunocompromised patients (p 0.03). Streptococcus pneumoniae was the most common
      causative organism in both groups (29% vs. 21%; p 0.08), followed by Legionella
      pneumophila (3% vs. 6%; p 0.01). Gram-negative bacilli were more frequent among
      immunocompromised patients (5% vs. 0.5%; p <0.01), particularly Pseudomonas
      aeruginosa (3% vs. 0%; p 0.04). Nocardiosis was only observed in
      immunocompromised patients (two cases). Bacteremia occurred similarly in the two
      groups. No significant differences were found with respect to ICU admission (8%,
      in both groups) or the length of stay (12.5 vs. 10.4 days). The early (<48 h)
      (3.5 vs. 0.5%; p 0.04) and overall case-fatality rates (12% vs. 3%; p <0.01) were
      higher in immunocompromised patients. In conclusion, a substantial number of
      older patients hospitalized for CAP are immunocompromised. Although relatively
      uncommon, CAP due to gram-negative bacilli, including P. aeruginosa, is more
      frequent among these patients. CAP occurring in immunocompromised patients causes
      significant morbidity and mortality.

PMID- 22390625
TI  - Exercise training after lung transplantation improves participation in daily
      activity: a randomized controlled trial.
AB  - The effects of exercise training after lung transplantation have not been studied
      in a randomized controlled trial so far. We investigated whether 3 months of
      supervised training, initiated immediately after hospital discharge, improve
      functional recovery and cardiovascular morbidity of patients up to 1 year after
      lung transplantation. Patients older than 40 years, who experienced an
      uncomplicated postoperative period, were eligible for this single blind, parallel
      group study. Sealed envelopes were used to randomly allocate patients to 3 months
      of exercise training (n = 21) or a control intervention (n = 19). Minutes of
      daily walking time (primary outcome), physical fitness, quality of life and
      cardiovascular morbidity were compared between groups adjusting for baseline
      assessments in a mixed models analysis. After 1 year daily walking time in the
      treated patients (n = 18) was 85 +/- 27 min and in the control group (n = 16) 54
      +/- 30 min (adjusted difference 26 min [95%CI 8-45 min, p = 0.006]). Quadriceps
      force (p = 0.001), 6-minute walking distance (p = 0.002) and self-reported
      physical functioning (p = 0.039) were significantly higher in the intervention
      group. Average 24 h ambulatory blood pressures were significantly lower in the
      treated patients (p <= 0.01). Based on these results patients should be strongly
      encouraged to participate in an exercise training intervention after lung
      transplantation.

PMID- 22390626
TI  - PDK1 regulates the generation of oligodendrocyte precursor cells at an early
      stage of mouse telencephalic development.
AB  - During the development of the mouse telencephalon, multipotent neural precursor
      cells (NPCs) generate oligodendrocyte precursor cells (OPCs), progenitors
      restricted to the oligodendrocyte lineage, at various sites in a developmental
      stage-dependent manner. Although substantial progress has been made in
      identifying the transcription factors that control the production of OPCs, the
      signaling pathways that regulate these transcription factors and the
      spatiotemporal pattern of OPC production have been only partially clarified.
      Here, we show that the serine-threonine kinase 3-phosphoinositide-dependent
      kinase 1 (PDK1) contributes to an early wave of OPC production in the developing
      mouse telencephalon. Ablation of PDK1 in NPCs resulted in a reduction in the
      number of OPCs positive for Sox10 and platelet-derived growth factor receptor
      alpha (PDGFRalpha) within the neocortex and striatum at embryonic day (E) 15.5,
      but not at E18.5. Furthermore, pharmacological inhibition of phosphoinositide 3
      kinase (PI3K) or deletion of the PDK1 gene suppressed the generation of OPCs from
      NPCs induced by fibroblast growth factor (FGF) 2 in culture. These results
      implicate the PI3K-PDK1 pathway in the physiological regulation of OPC production
      in a developmental context-dependent manner.

PMID- 22390627
TI  - Tyrosyl-DNA phosphodiesterase 1 inhibitor from an anamorphic fungus.
AB  - Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an enzyme that catalyzes hydrolysis of
      3'-phosphotyrosyl bonds and is involved in repair of irreversible topoisomerase I
      (Top1)-DNA covalent complexes. Tdp1 inhibitors are regarded as potential cancer
      therapeutics in combination with Top1 inhibitors, which are currently used to
      treat human cancers. While screening for Tdp1 inhibitors, we discovered a novel
      compound, JBIR-21 (1), from the culture of an anamorphic fungus, RF-13305. The
      structure of 1 was established by extensive NMR and MS analyses. Compound 1
      showed inhibitory activity against Tdp1 (IC(50) value, 18 MUM) and cytotoxic
      activity against cancer cell lines (IC(50) values, 3.5-13 MUM). Compound 1 also
      exhibited antitumor activity in a mouse xenograft model without adverse effects.

PMID- 22390628
TI  - Current anticoagulant safety.
AB  - INTRODUCTION: Currently used anticoagulants such as unfractionated heparin, low
      molecular-weight heparin and vitamin K antagonists, have several drawbacks,
      mostly related to safety. In this review, we will briefly discuss and compare the
      safety of anticoagulation therapy with 'old' and new agents. AREAS COVERED:
      Safety issues with anticoagulation therapy are mostly related to bleeding. The
      intensity of anticoagulation is related to the risk of bleeding and thus, for the
      efficacy not to be affected, must be maintained at the lower effective intensity.
      Several improvements have been made in the management of anticoagulation therapy;
      these include monitoring, pathology-based treatment schemes taking into account
      patient characteristics, patient education and the introduction of
      anticoagulation centers. Safety of novel anticoagulants is encouraging. EXPERT
      OPINION: Novel agents have the potential to compete with existing therapy for
      thromboprophylaxis, treatment and stroke prevention in atrial fibrillation.
      Promising results have emerged from trials comparing them with existing
      treatment. Not long from now we will see these new agents in the armamentarium of
      antithrombotic drugs.

PMID- 22390629
TI  - Establishment of canine hematology reference intervals for the Sysmex XT-2000iV
      hematology analyzer using a blood donor database.
AB  - BACKGROUND: The Sysmex XT-2000iV is a hematology analyzer that combines impedance
      and optical techniques and has been previously validated for dogs. Specific
      reference intervals (RIs) are useful when interpreting results. OBJECTIVES: The
      aim of this study was to determine hematologic RIs for the Sysmex XT-2000iV using
      a large reference population of client-owned clinically healthy blood donor dogs,
      adopting an indirect sampling method. METHODS: Dogs were screened for breed,
      size, health, travel history, and previous blood transfusions, and the quality of
      blood specimens was also reviewed. Results from specimens that met inclusion
      criteria were used to determine RIs using a nonparametric method. Specimens from
      Akitas and sighthounds were excluded from the study. RESULTS: Of 992 specimens
      that had been collected from blood donors and analyzed, 297 were initially
      included in the RI study. An additional 38 specimens were excluded as outliers,
      and hematologic RIs for the Sysmex XT-2000iV were based on analysis of specimens
      from 259 clinically healthy dogs. Measurands evaluated had variable
      distributions, and intervals obtained were generally comparable to previously
      reported RIs. Differences observed included higher lower and upper reference
      limits (LRL and URL, respectively) for MCV and lower URL for WBC count.
      Reticulocyte count and the LRL of the absolute lymphocyte count were also higher
      than previously reported, and the RI for platelet count was narrower and lower.
      CONCLUSIONS: Canine RIs for the Sysmex hematology analyzer were established using
      an indirect sampling method with reference individuals selected from a large
      database of client-owned clinically healthy blood donor dogs. For specimens
      included in this study, time from collection to analysis was similar to what
      veterinary commercial laboratories experience.

PMID- 22390630
TI  - Preoperative margin detection by digital dermoscopy in the traditional surgical
      excision of cutaneous squamous cell carcinomas.
AB  - BACKGROUND: The incomplete excision rate is a useful clinical and performance
      indicator, as it correlates with the treatment, the recurrence rate, the
      patient's morbidity and mortality. Methods of preoperative assessment of tumoral
      margins are therefore of paramount importance. Dermoscopy is a simple, non
      invasive method, and can also be used for the diagnosis of epithelial tumors.
      OBJECTIVE: The aim of the study is to assess the preoperative evaluation of
      margins with digital dermoscopy, and compare it with clinical evaluation; to
      ameliorate the surgical performance. PATIENTS AND METHODS: Ninety-four patients
      with histologically confirmed squamous cell carcinomas were initially selected
      for traditional surgical excision. Subsequently, the margin of excision was
      determined by both clinical (group A, 46 patients) and dermoscopy evaluation
      (group B, 48 patients). RESULTS: In group A, margin involvement was observed in
      eight (17%) patients. Positive margins were seen in three (6%) patients of group
      B. CONCLUSIONS: Preoperative digital dermoscopy is a better method for detecting
      tumoral margins than clinical evaluation, and is an effective, simple, non
      invasive method for the presurgical evaluation of margins.

PMID- 22390631
TI  - Water footprint of European cars: potential impacts of water consumption along
      automobile life cycles.
AB  - Due to global increase of freshwater scarcity, knowledge about water consumption
      in product life cycles is important. This study analyzes water consumption and
      the resulting impacts of Volkswagen's car models Polo, Golf, and Passat and
      represents the first application of impact-oriented water footprint methods on
      complex industrial products. Freshwater consumption throughout the cars' life
      cycles is allocated to material groups and assigned to countries according to
      import mix shares or location of production sites. Based on these regionalized
      water inventories, consequences for human health, ecosystems, and resources are
      determined by using recently developed impact assessment methods. Water
      consumption along the life cycles of the three cars ranges from 52 to 83
      m(3)/car, of which more than 95% is consumed in the production phase, mainly
      resulting from producing iron, steel, precious metals, and polymers. Results show
      that water consumption takes place in 43 countries worldwide and that only 10% is
      consumed directly at Volkswagen's production sites. Although impacts on health
      tend to be dominated by water consumption in South Africa and Mozambique,
      resulting from the production of precious metals and aluminum, consequences for
      ecosystems and resources are mainly caused by water consumption of material
      production in Europe.

PMID- 22390633
TI  - Masseter muscle changes following orthognathic surgery: a long-term three
      dimensional computed tomography follow-up.
AB  - OBJECTIVE: To evaluate the long-term changes of masseter muscle morphology in
      skeletal Class III patients with facial asymmetry following two-jaw orthognathic
      surgery (Le Fort I osteotomy + intraoral vertical ramus osteotomy). MATERIALS AND
      METHODS: Using computed tomography (CT), a longitudinal study was conducted on 17
      skeletal Class III patients with facial asymmetry. Measurements from the
      reconstructed three-dimensional (3D) CT images were compared from T1 (before
      surgery), T2 (1 year after surgery), and T3 (4 years after surgery). The maximum
      cross-sectional area (CSA), orientation, thickness, and width of the masseter
      muscle were measured on both the deviated and nondeviated sides. The control
      group included 17 volunteers with skeletal and dental Class I relationships
      without dentofacial deformities. RESULTS: At T1, there were no significant
      differences in CSA, thickness, or width of masseter muscle between the deviated
      and nondeviated sides. Masseter muscle orientation was significantly more
      vertical on the nondeviated side than on the deviated side at T1 (P < .01); no
      significant bilateral differences were noted at T2 and T3. At T1, masseter muscle
      measurements were significantly lower than controls (P < .01). During T1-T3, a
      significant increase was noted in CSA, thickness, and width (P < .01) of masseter
      muscle. At T3, no significant difference was noted between the study and control
      groups. CONCLUSION: After surgery, the masseter muscle measurements of skeletal
      Class III asymmetry patients showed no significant differences compared with the
      control group within the 4-year follow-up period, indicating adaptation to the
      new skeletal environments and increased functional demand.

PMID- 22390632
TI  - Effects of different intracoronal bleaching methods on shear bond strengths of
      orthodontic brackets.
AB  - OBJECTIVE: To evaluate the effects of different intracoronal bleaching methods on
      the shear bond strengths (SBS) of orthodontic brackets. MATERIALS AND METHODS:
      Sixty freshly extracted mandibular incisors were randomly divided into four
      groups (n = 15 per group). After filling the root canals, root fillings were
      removed 2 mm apical to the cementoenamel junction, and a 2-mm-thick layer of zinc
      phosphate cement base was applied. Group 1 served as the control. Intracoronal
      bleaching was performed with hydrogen peroxide (Opalacence Endo, Ultradent
      products Inc, South Jordan, Utah) in group 2, sodium perborate (Sultan
      Healthcare, Englewood, NJ) in group 3, and 37% carbamide peroxide (Whiteness
      Super Endo, Dentscare, ltda, Joinville, Brazil) in group 4. Orthodontic brackets
      were bonded with a light cure composite resin and cured with an LED light. After
      bonding, the SBS of the brackets was tested with a Universal testing machine.
      RESULTS: Analysis of variance indicated a significant difference between groups
      (P < .001). The highest values for SBS were measured in group 1 (10.15 +/- 1.15
      MPa). The SBS was significantly lower in groups 2, 3, and 4 than in group 1 (P <
      .001). The lowest values for SBS were measured in group 3 (6.17 +/- 0.85 MPa).
      SBS was significantly higher in group 4 than in group 3 (P < .05). CONCLUSIONS:
      Intracoronal bleaching significantly affected the SBS of orthodontic brackets on
      human enamel. Bleaching with sodium perborate affects SBS more adversely than
      does bleaching with other agents.

PMID- 22390634
TI  - Factors affecting stresses in cortical bone around miniscrew implants: a three
      dimensional finite element study.
AB  - OBJECTIVE: To evaluate various types of stress in cortical bone around miniscrew
      implants using finite element analysis. MATERIALS AND METHODS: Twenty-six three
      dimensional assemblies of miniscrew models placed in alveolar bone blocks were
      constructed using Abaqus (Dassault Systemes Simulia Corp, Providence, RI), a
      commercial finite element analysis software package. The model variables included
      implant design factors and bone-related factors. All miniscrew implants were
      loaded in the mesial direction with a linear force equal to 2 N. Peak von Mises
      and principal stress values in cortical bone were compared between the different
      models for each factor. RESULTS: The results demonstrated that some factors
      affected the stresses in bone (implant diameter, implant head length, thread
      size, and elastic modulus of cancellous bone), while other factors did not
      (thread shape, thread pitch, and cortical bone thickness). CONCLUSIONS: Miniscrew
      implant diameter, head length, and thread size as well as the elastic modulus of
      cancellous bone affect the stresses in cortical bone layer surrounding the
      miniscrew implant and may therefore affect its stability.

PMID- 22390635
TI  - Community analysis of high- and low-nucleic acid-containing bacteria in NW
      Mediterranean coastal waters using 16S rDNA pyrosequencing.
AB  - The ecological significance of the marine bacterial populations distinguishable
      by flow cytometry on the basis of the fluorescence (FL) of their nucleic acid
      (NA) content and proxies of cell size (such as side scatter, SSC) remains largely
      unknown. Some studies have suggested that cells with high NA (HNA) content and
      high SSC (HS) represent the active members of the community, while the low NA
      (LNA) cells are inactive members of the same phylogenetic groups. But group
      specific activity measurements and phylogenetic assignment after cell sorting
      have suggested this is not be the case, particularly in open-ocean communities.
      To test the extent to which the different NA subgroups are similar, and
      consequently the extent to which they likely have similar ecological and
      biogeochemical roles in the environment, we analysed the phylogenetic composition
      of three populations after cell sorting [high NA-high SC (HNA-HS), high NA-low SC
      (HNA-LS), low NA (LNA)] by 454 pyrosequencing in two contrasting periods of the
      year in NW Mediterranean coastal waters (BBMO, Blanes Bay Microbial Observatory)
      where these three populations have recurrent seasonal patterns. Statistical
      analyses showed that summer and winter samples were significantly different and,
      importantly, the sorted populations within a sample were composed of different
      taxa. The majority of taxa were associated with one NA fraction only, and the
      degree of overlap (i.e. OTUs present simultaneously in 2 fractions) between HNA
      and LNA and between summer and winter communities was very small.
      Rhodobacterales, SAR116 and Bacteroidetes contributed primarily to the HNA
      fraction, whereas other groups such as SAR11 and SAR86 contributed largely to the
      LNA fractions. Gammaproteobacteria other than SAR86 showed less preference for
      one particular NA fraction. An increase in diversity was observed from the LNA to
      the HNA-HS fraction for both sample dates. Our results suggest that, in Blanes
      Bay, flow cytometric signatures of natural communities track their phylogenetic
      composition.

PMID- 22390636
TI  - Modelling malaria treatment practices in Bangladesh using spatial statistics.
AB  - BACKGROUND: Malaria treatment-seeking practices vary worldwide and Bangladesh is
      no exception. Individuals from 88 villages in Rajasthali were asked about their
      treatment-seeking practices. A portion of these households preferred malaria
      treatment from the National Control Programme, but still a large number of
      households continued to use drug vendors and approximately one fourth of the
      individuals surveyed relied exclusively on non-control programme treatments. The
      risks of low-control programme usage include incomplete malaria treatment,
      possible misuse of anti-malarial drugs, and an increased potential for drug
      resistance. METHODS: The spatial patterns of treatment-seeking practices were
      first examined using hot-spot analysis (Local Getis-Ord Gi statistic) and then
      modelled using regression. Ordinary least squares (OLS) regression identified key
      factors explaining more than 80% of the variation in control programme and vendor
      treatment preferences. Geographically weighted regression (GWR) was then used to
      assess where each factor was a strong predictor of treatment-seeking preferences.
      RESULTS: Several factors including tribal affiliation, housing materials,
      household densities, education levels, and proximity to the regional urban
      centre, were found to be effective predictors of malaria treatment-seeking
      preferences. The predictive strength of each of these factors, however, varied
      across the study area. While education, for example, was a strong predictor in
      some villages, it was less important for predicting treatment-seeking outcomes in
      other villages. CONCLUSION: Understanding where each factor is a strong predictor
      of treatment-seeking outcomes may help in planning targeted interventions aimed
      at increasing control programme usage. Suggested strategies include providing
      additional training for the Building Resources across Communities (BRAC) health
      workers, implementing educational programmes, and addressing economic factors.

PMID- 22390637
TI  - A versatile synthesis method of dendrites-free segmented nanowires with a precise
      size control.
AB  - We report an innovative strategy to obtain cylindrical nanowires combining well
      established and low-cost bottom-up methods such as template-assisted nanowires
      synthesis and electrodeposition process. This approach allows the growth of
      single-layer or multi-segmented nanowires with precise control over their length
      (from few nanometers to several micrometers). The employed techniques give rise
      to branched pores at the bottom of the templates and consequently dendrites at
      the end of the nanowires. With our method, these undesired features are easily
      removed from the nanowires by a selective chemical etching. This is crucial for
      magnetic characterizations where such non-homogeneous branches may introduce
      undesired features into the final magnetic response. The obtained structures show
      extremely narrow distributions in diameter and length, improved robustness and
      high-yield, making this versatile approach strongly compatible with large scale
      production at an industrial level. Finally, we show the possibility to tune
      accurately the size of the nanostructures and consequently provide an easy
      control over the magnetic properties of these nanostructures.

PMID- 22390638
TI  - Quality of life in atopic dermatitis: Changes over 6 years in patients who report
      persistent eczema.

PMID- 22390639
TI  - Antigen-antibody interactions and structural flexibility of a femtomolar-affinity
      antibody.
AB  - The femtomolar-affinity mutant antibody (4M5.3) generated by directed evolution
      is interesting because of the potential of antibody engineering. In this study,
      the mutant and its wild type (4-4-20) were compared in terms of antigen-antibody
      interactions and structural flexibility to elucidate the effects of directed
      evolution. For this purpose, multiple steered molecular dynamics (SMD)
      simulations were performed. The pulling forces of SMD simulations elucidated the
      regions that form strong attractive interactions in the binding pocket.
      Structural analysis in these regions showed two important mutations for improving
      attractive interactions. First, mutation of Tyr102(H) to Ser (sequence numbering
      of Protein Data Bank entry  1FLR ) played a role in resolving the steric
      hindrance on the pathway of the antigen in the binding pocket. Second, mutation
      of Asp31(H) to His played a role in resolving electrostatic repulsion. Potentials
      of mean force (PMFs) of both the wild type and the mutant showed landscapes that
      do not include obvious intermediate states and go directly to the bound state.
      These landscapes were regarded as funnel-like binding free energy landscapes.
      Furthermore, the structural flexibility based on the fluctuations of the
      positions of atoms was analyzed. It was shown that the fluctuations in the
      positions of the antigen and residues in contact with antigen tend to be smaller
      in the mutant than in the wild type. This result suggested that structural
      flexibility decreases as affinity is improved by directed evolution. This
      suggestion is similar to the relationship between affinity and flexibility for in
      vivo affinity maturation, which was suggested by Romesberg and co-workers
      [Jimenez, R., et al. (2003) Proc. Natl. Acad. Sci. U.S.A.100, 92-97].
      Consequently, the relationship was found to be applicable up to femotomolar
      affinity levels.

PMID- 22390641
TI  - Inflammation in ischemic stroke subtypes.
AB  - Determining the cause of stroke does influence choices for management.
      categorization of subtypes of ischemic stroke has had considerable study, but
      definitions are hard to formulate and their application for diagnosis in an
      individual patient is often problematic. Cerebral ischemia initiates a complex
      cascade of events at genomic, molecular, and cellular levels, and inflammation is
      important in this cascade. In 1993 for For the Trial of Org 10172 in Acute Stroke
      Treatment (TOAST), Adams et al] conducted a placebo-controlled, randomized,
      blinded study of the low-molecular-weight heparinoid given to patients within 24
      hours after stroke and developed a system for diagnosis of subtype of ischemic
      stroke that uses components of existing diagnostic schemes. The type of acute
      ischemic stroke was classified according to the TOAST classification: 1) Large
      Artery AtheroSclerosis (LAAS); 2) CardioEmbolic Infarct (CEI); 3) LACunar infarct
      (LAC); 4) stroke of Other Determined Etiology (ODE); 5) stroke of UnDetermined
      Etiology (UDE) (see Fig. (1)). On the basis of pathophysiologic differences of
      each stroke subtype it's possible to hypothesize a different pattern of immuno
      inflammatory activation in relation of ischemic stroke subtype. A nonspecific
      systemic inflammatory response occurs after both ischemic and hemorrhagic stroke,
      either as part of the process of brain damage or in response to complications
      such as deep venous thrombosis. Several studies have reported that higher levels
      of inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6)
      are associated with worse outcome after ischemic stroke. Our group reported that
      patients with cardioembolic subtype showed significantly higher median plasma
      levels of TNF-alpha, IL-6, IL-1beta whereas the lacunar subtype showed
      significantly lower median plasma levels of TNF-alpha, IL-6 and IL-1beta. Our
      findings underlined the significant association was noted between the severity of
      neurological deficit at admission, the diagnostic subtype and some inflammatory
      variables.

PMID- 22390640
TI  - Differential regulation of osteoclastogenesis by Notch2/Delta-like 1 and
      Notch1/Jagged1 axes.
AB  - INTRODUCTION: Osteoclastogenesis plays an important role in the bone erosion of
      rheumatoid arthritis (RA). Recently, Notch receptors have been implicated in the
      development of osteoclasts. However, the responsible Notch ligands have not been
      identified yet. This study was undertaken to determine the role of individual
      Notch receptors and ligands in osteoclastogenesis. METHODS: Mouse bone marrow
      derived macrophages or human peripheral blood monocytes were used as osteoclast
      precursors and cultured with receptor activator of nuclear factor-kappaB ligand
      (RANKL) and macrophage-colony stimulating factor (M-CSF) to induce osteoclasts.
      Osteoclasts were detected by tartrate-resistant acid phosphatase (TRAP) staining.
      K/BxN serum-induced arthritic mice and ovariectomized mice were treated with anti
      mouse Delta-like 1 (Dll1) blocking monoclonal antibody (mAb). RESULTS: Blockade
      of a Notch ligand Dll1 with mAb inhibited osteoclastogenesis and, conversely,
      immobilized Dll1-Fc fusion protein enhanced it in both mice and humans. In
      contrast, blockade of a Notch ligand Jagged1 enhanced osteoclastogenesis and
      immobilized Jagged1-Fc suppressed it. Enhancement of osteoclastogenesis by
      agonistic anti-Notch2 mAb suggested that Dll1 promoted osteoclastogenesis via
      Notch2, while suppression by agonistic anti-Notch1 mAb suggested that Jagged1
      suppressed osteoclastogenesis via Notch1. Inhibition of Notch signaling by a
      gamma-secretase inhibitor suppressed osteoclastogenesis, implying that
      Notch2/Dll1-mediated enhancement was dominant. Actually, blockade of Dll1
      ameliorated arthritis induced by K/BxN serum transfer, reduced the number of
      osteoclasts in the affected joints and suppressed ovariectomy-induced bone loss.
      CONCLUSIONS: The differential regulation of osteoclastogenesis by Notch2/Dll1 and
      Notch1/Jagged1 axes may be a novel target for amelioration of bone erosion in RA
      patients.

PMID- 22390642
TI  - Effects of physical exercise on inflammatory markers of atherosclerosis.
AB  - It is well established that physically fit individuals have a reduced risk of
      developing CVD (cardiovascular disease) and other age-related chronic disorders.
      Regular exercise is an established therapeutic intervention with an enormous
      range of benefits. Chronic low-grade systemic inflammation may be involved in
      atherosclerosis, diabetes and in pathogenesis of several chronic pathological
      conditions; recent findings confirm that physical activity induces an increase in
      the systemic levels of a number of cytokines and chemokines with anti
      inflammatory properties. The possibility that regular physical exercise exerts
      anti-inflammation activity, being the interaction between contracting muscle and
      the other tissues and the circulating cells mediated through signals transmitted
      by "myokines" produced with muscle contractions. To date the list of myokines
      includes IL-6, IL-8, and IL-15. During muscle contractions are also released IL-1
      receptor antagonis and sTNF-R, molecules that contribute to provide anti
      inflammatory actions. Nevertheless discrepancies, analysis of available
      researches seem to confirm the efficacy of regular physical training as a
      nonpharmacological therapy having target chronic low-grade inflammation. Given
      this, physical exercise could be considerate a useful weapon against local
      vascular and systemic inflammation in atherosclerosis. Several mechanisms explain
      the positive effect of chronic exercise, nevertheless, these mechanisms do not
      fully enlighten all pathways by which exercise can decrease inflammation and
      endothelial dysfunction, and hence modulate the progression of the underlying
      disease progress.

PMID- 22390643
TI  - Atherosclerosis as an inflammatory disease.
AB  - In many ways, atherosclerosis is a chronic inflammatory disorder and this issue
      is confirmed by recent investigations of that have focused on inflammation,
      providing new insight into mechanisms of disease. Several recent studies have
      addressed the role of chemokines in leukocyte accumulation in atherosclerosis,
      extending our knowledge and understanding of the complex and cell type-specific
      functions of chemokines in atherosclerosis. Activated T-lymphocytes within the
      atherosclerotic vessel wall express the CD40 ligand surface molecule, known to
      play a major role in several immunological pathways. In addition to activated T
      lymphocytes, functional CD40 and CD40L are coexpressed by human vascular
      endothelial cells, smooth muscle cells and human macrophages in vitro as well as
      in situ in human atherosclerotic lesions. Recent studies indicate that CD40L
      activates atheroma-associated cells by promoting the expression of molecules
      thought to be involved in atherosclerosis, such as adhesion molecules, cytokines,
      matrix metalloproteinases, and tissue factor. Atherosclerosis starts with an
      innate immune response involving the recruitment and activation of monocytes
      macrophages that respond to an excessive accumulation of modified lipids within
      the arterial wall, followed by an adaptive immune response involving antigen
      specific T lymphocytes. Effector T cells recognize modified auto-antigens such as
      oxidized LDL and heat shock proteins (i.e. HSP-60) that are presented by antigen
      presenting cells such as macrophages or dendritic cells. The accumulation of
      inflammatory cells within the arterial wall leads to local production of
      chemokines, interleukins and proteases that enhance the influx of monocytes and
      lymphocytes, thereby promoting the progression of atherosclerotic lesions Recent
      reports have helped explain some of these questions by pointing to a role of
      contact dependent interaction between CD40 and CD40 ligand (CD40L, renamed CD154)
      as a stimulus for atheroma-associated cells. Also Macrophages play important
      roles in the progression of atherosclerosis by exhibiting unique characteristics
      under the various stimuli, evolving the plaque instability, thrombus formation
      and remodeling. Macrophage recruitment by abnormal endothelium over developing
      atherosclerotic plaques, is aided by endothelial expression of adhesion molecules
      (ICAM-1, VCAM, ELAM). The knowledge of atherosclerosis as an inflammatory disease
      offers the opportunity to develop novel therapeutic strategies targeting the
      inflammatory component of the disease.

PMID- 22390644
TI  - Inflammation in peripheral arterial disease (PAD).
AB  - Peripheral arterial disease (PAD) affects a large number of individuals over the
      age of 55 years old, and data from studies has shown a relationship between
      inflammation, and PAD. Many researchers have not only focused on the role played
      by inflammatory biomarkers and the progression of PAD, but also on the efficiency
      of biomarkers in monitoring medical, surgical and interventional strategies in
      PAD patients. In this review, Authors aim to demonstrate that biomarkers play a
      key role in the pathophysiology of PAD, and consequently they could be screened
      to highlight individuals showing these crucial pathophysiological signs. Based on
      a large debate about phlogosis, it is now considered to be a relevant objective
      in reducing the prevalence and consequences of atherosclerotic diseases such as
      PAD. Finally, efforts must be made towards addressing this very important
      objective, and consequently a greater number of studies need to be made in
      combatting phlogosis, especially among PAD patients.

PMID- 22390645
TI  - Inflammation in coronary artery disease and acute myocardial infarction - is the
      stage set for novel therapies?
AB  - Acute myocardial infarction (AMI) constitutes the major cause of death in most
      nations and death rates and morbidity remain substantial in the years thereafter.
      Inflammation is a hallmark throughout the distinct stages of atherosclerotic
      lesion formation preceding AMI as well as at the time of plaque rupture and
      during the post-infarct repair phase. Epidemiological, genetic, clinical and
      experimental evidence converges on inflammation as a pivotal factor in disease
      progression and exacerbation. Harnessing its harmful consequences constitutes an
      attractive therapeutic approach to address this unmet medical need. Components of
      the innate and adaptive immune system with the characteristic cytokines
      interleukin-1 and tumor necrosis factor-alpha, respectively exert prominent
      functions in atherogenesis and post-infarct remodeling. Leukocyte subsets of the
      monocyte/macrophage and CD4(+) T lymphocyte cell lineage interacting with a vast
      array of cells comprising platelets, neutrophils, dendritic cells, mast cells,
      vascular smooth muscle cells and fibroblasts orchestrate the inflammatory
      pathophysiology underlying plaque progression in the vasculature and fibrotic
      repair of the infarct. This pathophysiology is amenable to modification by drugs
      targeting cell proliferation, cell migration, osteogenic/fibrous turnover of the
      extracellular matrix ranging from antimetabolites, glucocorticoids, specific
      cytokine and leukotriene antagonists to classic immunosuppressive agents and
      vaccines directed specifically at certain disease-relevant antigens. Based on
      published data on clinical safety and clinical/experimental efficacy in
      inhibiting disease progression this review covers recent advances in this field
      and aims to propose candidate drugs for future clinical trials.

PMID- 22390646
TI  - Acute coronary syndromes as auto-inflammatory disorders.
AB  - From the onset to the healing stage of acute coronary syndromes, an endless
      inflammation has been presented with complex, multiple cross-talk mechanisms at
      the molecular, cellular, and organ levels. Even though the early reperfusion
      treatment either by thrombolysis or percutaneous coronary intervention provides
      the excellent clinical benefits in patients with acute coronary syndromes,
      ischemia/ reperfusion injury may somewhat offset those great advantages.
      Inflammation, although potentially protective, has been deeply associated with
      those detrimental conditions. The hexagonal vascular inflammatory network which
      is composed of activated various leukocytes, vascular endothelial cells, vascular
      smooth muscle cells, platelets, excess reactive oxygen species, and cholesterol
      may contribute these vicious circles. To address these complex syndromes with
      more benefits regarding the prevention and treatment, this review comprehensively
      updates the pathogenesis of acute coronary syndromes from the view points of
      vascular inflammation.

PMID- 22390647
TI  - Episiotomy characteristics and risks for obstetric anal sphincter injuries: a
      case-control study.
AB  - OBJECTIVES: To investigate the association between the geometrical properties of
      episiotomy and obstetric anal sphincter injuries (OASIS) because episiotomies
      angled at 40-60 degrees  are associated with fewer OASIS than episiotomies with
      more acute angles. DESIGN: Case-control study. SETTING: University Hospital of
      North Norway, Tromso and Nordland Hospital, Bodo, Norway. SAMPLE: Seventy-four
      women who had one vaginal birth and episiotomy. Cases (n = 37) have sustained
      OASIS at birth, while controls (n = 37) had not. The groups were matched for
      instrumental delivery. METHODS: Two groups of women with history of only one
      vaginal birth were compared. Episiotomy scar was identified and photographed and
      relevant measures were taken. Data were analysed using conditional logistic
      analysis. MAIN OUTCOME MEASURES: Mean episiotomy angle, length, depth, incision
      point. RESULTS: The risk of sustaining OASIS decreased by 70% (odds ratio [OR]
      0.30; 95% CI 0.14-0.66) for each 5.5-mm increase in episiotomy depth, decreased
      by 56% (OR 0.44; 95% CI 0.23-0.86) for each 4.5-mm increase in the distance from
      the midline to the incision point of the episiotomy, and decreased by 75% (OR
      0.25; 95% CI 0.10-0.61) for each 5.5-mm increase in episiotomy length. Lastly,
      there was no difference in mean angle between groups but there was a "U-shaped"
      association between angle and OASIS (OR 2.09; 95% CI 1.02-4.28) with an increased
      risk (OR 9.00; 95% CI 1.1-71.0) of OASIS when the angle was either smaller than
      15 degrees  or >60 degrees . CONCLUSION: The present study showed that scarred
      episiotomies with depth > 16 mm, length > 17 mm, incision point > 9 mm lateral of
      midpoint and angle range 30-60 degrees  are significantly associated with less
      risk of OASIS. Shrinkage of tissue must be considered.

PMID- 22390648
TI  - Association between obesity at diagnosis and weight change during induction and
      survival in pediatric acute lymphoblastic leukemia.
AB  - For children with acute lymphoblastic leukemia (ALL), the impact of obesity at
      diagnosis and weight change during induction on survival is uncertain. Objectives
      of this study were to describe the relationship between obesity and weight change
      during induction and event-free survival (EFS) and overall survival (OS).
      Participants were children 2-18 years old with ALL diagnosed between January 2001
      and September 2006. Univariate and multiple regression analyses were conducted.
      In total 238 children were included; 21 (8.8%) were obese at diagnosis. Obese
      patients, compared with non-obese patients, had lower 5-year EFS (62.2+/-12.1%
      vs. 83.6+/-2.6%; p =0.02) and OS (80.7+/-8.7% vs. 92.9+/-1.9%; p =0.005). In
      univariate analysis, weight gain during induction was associated with better EFS
      (hazard ratio [HR] =0.89, 95% confidence interval [CI] 0.82-0.97; p =0.009) and
      OS (HR =0.81, 95% CI 0.74-0.90; p <0.0001). Obese pediatric patients with ALL
      have inferior survival while increased weight during induction may be associated
      with better survival. Causes of weight loss during induction should be
      aggressively managed.

PMID- 22390650
TI  - To provide care and be cared for in a multiple-bed hospital room.
AB  - AIMS: To illuminate patients' experiences of being cared for and nurses'
      experiences of caring for patients in a multiple-bed hospital room. BACKGROUND:
      Many patients and healthcare personnel seem to prefer single-bed hospital rooms.
      However, certain advantages of multiple-bed hospital rooms (MBRs) have also been
      described. METHOD: Eight men and eight women being cared for in a multiple
      bedroom were interviewed, and two focus-group interviews (FGI) with 12 nurses
      were performed. A qualitative content analysis was used. RESULTS: One theme-
      Creating a sphere of privacy--and three categories were identified based on the
      patient interviews. The categories were: Being considerate, Having company and
      The patients' area. In the FGI, one theme--Integrating individual care with care
      for all--and two categories emerged: Experiencing a friendly atmosphere and
      Providing exigent care. Both patients and nurses described the advantages and
      disadvantages of multiple-bed rooms. The patient culture of taking care of one
      another and enjoying the company of room-mates were considered positive and gave
      a sense of security of both patients and nurses. The advantages were slight and
      could easily become disadvantages if, for example, room-mates were very ill or
      confused. The patients tried to maintain their privacy and dignity and claimed
      that there were small problems with room-mates listening to conversations. In
      contrast, the nurses stressed patient integrity as a main disadvantage and worked
      to protect the integrity of individual patients. Providing care for all patients
      simultaneously had the advantage of saving time. CONCLUSIONS: The insights gained
      in the present study could assist nurses in reducing the disadvantages and taking
      advantage of the positive elements of providing care in MBRs. Health
      professionals need to be aware of how attitudes towards male and female patients,
      respectively, could affect care provision.

PMID- 22390652
TI  - Emerging therapies for treatment of acute lung injury and acute respiratory
      distress syndrome.
AB  - In 2007, Bosma et. al provided a comprehensive review of emerging therapies for
      the acute respiratory distress syndrome (ARDS), a condition which continues to
      carry a mortality rate of greater than 30%. Over the past several years, the
      development of novel and effective therapeutic agents for ARDS remains
      disappointing, and unfortunately, no recent therapeutic interventions have
      demonstrated a clear benefit. Herein, the results of several of these early and
      late phase clinical trials are reviewed, the majority of which address known
      maladaptive processes that have been deemed critical in ARDS pathophysiology.
      Based on the ongoing futility of current therapeutic models to yield effective
      therapies, it is speculated whether or not novel treatment paradigms, which
      address distinctly different aspects of this disease paradigm, may be warranted.

PMID- 22390651
TI  - CMV late phase-induced mTOR activation is essential for efficient virus
      replication in polarized human macrophages.
AB  - Human cytomegalovirus (CMV) remains one of the most important pathogens following
      solid-organ transplantation. Mounting evidence indicates that mammalian target of
      rapamycin (mTOR) inhibitors may decrease the incidence of CMV infection in solid
      organ recipients. Here we aimed at elucidating the molecular mechanisms of this
      effect by employing a human CMV (HCMV) infection model in human macrophages,
      since myeloid cells are the principal in vivo targets of HCMV. We demonstrate a
      highly divergent host cell permissiveness for HCMV with optimal infection
      susceptibility in M2 but not M1 polarized macrophages. Employing an ultrahigh
      purified HCMV stock we observed rapamycin-independent viral entry and induction
      of IFN-beta transcripts, but no proinflammatory cytokines or mitogen-activated
      protein kinases and mTOR activation early after infection. However, in the late
      infection phase, sustained mTOR activation was observed in HCMV-infected cells
      and was required for efficient viral protein synthesis including the viral late
      phase proteins pUL-44 and pp65. Accordingly, rapamycin strongly suppressed CMV
      replication 3 and 5 days postinfection in macrophages. In conclusion, these data
      indicate that mTOR is essential for virus replication during late phases of the
      viral cycle in myeloid cells and might explain the potent anti-CMV effects of
      mTOR inhibitors after organ transplantation.

PMID- 22390653
TI  - Isolation of Kingella kingae in the oropharynx during K. kingae arthritis in
      children.
AB  - Kingella kingae arthritis in children is now mainly diagnosed by PCR, which has
      surpassed conventional culture of joint fluid. As oropharynx colonization is the
      first step of Kingella kingae invasion, we prospectively investigated the
      possibility of cultivating it from throat swabs, in children hospitalized for K.
      kingae arthritis. Throat culture was 5.6-fold more sensitive than joint fluid
      cultures in isolating K. kingae (66.7% vs. 11.9% respectively, p <0.001) and may
      be used to perform antibiotic susceptibility testing.

PMID- 22390654
TI  - Potential energy surface and matrix isolation FT-IR study of isoleucine.
AB  - The conformational landscape of isoleucine was investigated by a theoretical DFT
      and MP2 study. This investigation has revealed new important conformations in
      comparison to a previous study. Five conformations have been predicted with an
      abundance larger than 5% at both levels of theory. Among these, three different
      types of amino acid backbone were present, each characterized by a typical
      intramolecular H-bond. Due to the H-bonding, the frequencies of the involved
      groups are strongly shifted, and these modes were probably observed with FT-IR
      spectroscopy in an Ar matrix. The experimental abundances could be estimated and
      were in good accordance with the MP2 stabilities, whereas the accordance with the
      DFT abundances was poor. In contrast to this, the correspondence of the DFT and
      the experimental frequencies was excellent, as demonstrated by the mean frequency
      deviation of only 4.7 cm(-1).

PMID- 22390655
TI  - Dopaminergic and prefrontal contributions to reward-based learning and outcome
      monitoring during child development and aging.
AB  - In many instances, children and older adults show similar difficulties in reward
      based learning and outcome monitoring. These impairments are most pronounced in
      situations in which reward is uncertain (e.g., probabilistic reward schedules)
      and if outcome information is ambiguous (e.g., the relative value of outcomes has
      to be learned). Furthermore, whereas children show a greater sensitivity to
      external outcome information, older adults focus less on a rapid differentiation
      of rewarding outcomes. In this article, we review evidence for the idea that
      these phenomenologically similar impairments in learning and outcome monitoring
      in children and older adults can be attributed to deficits in different
      underlying neurophysiological mechanisms. We propose that in older adults
      learning impairments are the result of reduced dopaminergic projections to the
      ventromedial prefrontal cortex, which lead to less differentiated representations
      of reward value. In contrast, in children, impairments in learning can be
      primarily attributed to deficits in executive control, which may be due to a
      protracted development of the dorsal medial and lateral prefrontal cortices. We
      think that this framework maps well onto recent neurophysiological models of
      reward processing and is plausible from a broader developmental perspective.

PMID- 22390656
TI  - Sex differences in reaction time mean and intraindividual variability across the
      life span.
AB  - Men are often found to have faster and less variable reaction times (RTs) than do
      women. However, it has not been established whether these differences occur in
      children. One suggestion is that sex differences in RT variability may be due to
      the effect of sex hormones on the brain and, by implication, may be expected in
      adults but not in children. The present study investigates sex differences in RT
      mean and intraindividual variability in a sample that includes both children and
      adults (age range = 4-75 years). Mean and intraindividual variability of simple
      RT (SRT) and 4-choice RT (CRT) were measured in 1,994 visitors to science
      festivals held in Edinburgh, Scotland, in 2008 and 2009 and in Cheltenham and
      Cambridge, England, in 2008. The commonly reported pattern of decreasing RT mean
      and variability in childhood and adolescence, followed by an increase in mean and
      variability through adulthood and into old age, was confirmed. Greater
      intraindividual variability for females in SRT and CRT was observed in adults but
      not in children. Males had significantly faster mean SRT than did females across
      the life span, but there were no sex differences in mean CRT.

PMID- 22390657
TI  - Peer network drinking predicts increased alcohol use from adolescence to early
      adulthood after controlling for genetic and shared environmental selection.
AB  - Research consistently links adolescents' and young adults' drinking with their
      peers' alcohol intake. In interpreting this correlation, 2 essential questions
      are often overlooked. First, which peers are more important, best friends or
      broader social networks? Second, do peers cause increased drinking, or do young
      people select friends whose drinking habits match their own? The present study
      combines social network analyses with family (twin and sibling) designs to answer
      these questions via data from the National Longitudinal Study of Adolescent
      Health. Analysis of peer nomination data from 134 schools (n = 82,629) and 1,846
      twin and sibling pairs shows that peer network substance use predicts changes in
      drinking from adolescence into young adult life even after controlling for
      genetic and shared environmental selection, as well as best friend substance use.
      This effect was particularly strong for high-intensity friendships. Although the
      peer-adolescent drinking correlation is partially explained by selection, the
      present finding offers powerful evidence that peers also cause increased
      drinking.

PMID- 22390658
TI  - Female and male adolescents' subjective orientations to mathematics and the
      influence of those orientations on postsecondary majors.
AB  - Although important strides toward gender parity have been made in several
      scientific fields, women remain underrepresented in the physical sciences,
      engineering, mathematics, and computer sciences (PEMCs). This study examines the
      effects of adolescents' subjective orientations, course taking, and academic
      performance on the likelihood of majoring in PEMC in college. Results indicate
      that racial-ethnic and gender underrepresentation in science, technology,
      engineering, and mathematics (STEM) fields are interrelated and should be
      examined with attention to the intersecting factors influencing female and racial
      ethnic minority adolescents' pathways toward careers in these fields. Among those
      who major in PEMC fields, women closely resemble men with respect to their
      subjective orientations. The effects of subjective orientations on women's
      chances of majoring in PEMC vary by their secondary school mathematics course
      completion levels. Women who take more mathematics courses are more likely to
      major in PEMC; however, course taking alone does not attenuate gender disparities
      in declaring these majors. High mathematics ability (as measured by standardized
      test scores in the 10th grade) appears to be positively associated with women's
      selection of social, behavioral, clinical, and health science majors. This
      association is less robust (and slightly negative) for women in PEMC. While
      advanced course taking appears to assist women in selecting PEMC majors, women
      who enter these fields may not be as strong as those who select other, less male
      dominated scientific fields.

PMID- 22390659
TI  - The relation between spatial skill and early number knowledge: the role of the
      linear number line.
AB  - Spatial skill is highly related to success in math and science (e.g., Casey,
      Nuttall, Pezaris, & Benbow, 1995). However, little work has investigated the
      cognitive pathways by which the relation between spatial skill and math
      achievement emerges. We hypothesized that spatial skill plays a crucial role in
      the development of numerical reasoning by helping children to create a spatially
      meaningful, powerful numerical representation-the linear number line. In turn, a
      strong linear number representation improves other aspects of numerical knowledge
      such as arithmetic estimation. We tested this hypothesis using 2 longitudinal
      data sets. First, we found that children's spatial skill (i.e., mental
      transformation ability) at the beginning of 1st and 2nd grades predicted
      improvement in linear number line knowledge over the course of the school year.
      Second, we found that children's spatial skill at age 5 years predicted their
      performance on an approximate symbolic calculation task at age 8 and that this
      relation was mediated by children's linear number line knowledge at age 6. The
      results are consistent with the hypothesis that spatial skill can improve
      children's development of numerical knowledge by helping them to acquire a linear
      spatial representation of numbers.

PMID- 22390661
TI  - Attachment-related differences in perceptions of an initial peer interaction
      emerge over time: evidence of reconstructive memory processes in adolescents.
AB  - This study examined whether attachment, assessed using the Adult Attachment
      Interview (AAI; George, Kaplan, & Main, 1996) was linked to how adolescents
      reconstructed their memory for an initial interaction with an unfamiliar peer.
      Adolescents (N = 189, 62% female) completed a 10-min laboratory task with a
      student whom they did not know. Immediately following this task, adolescents
      rated their perceptions of the interaction. Adolescents completed the same
      perception measure 2 weeks later. Although adolescents classified as secure and
      insecure on the AAI did not differ in how they perceived unfamiliar peers
      initially, attachment-related differences emerged over time. Insecure adolescents
      remembered the interactions as less positive and more negative and also reported
      being treated with greater hostility than they had initially reported 2 weeks
      earlier. In contrast, secure adolescents' memories for the negative aspects of
      the interaction and for hostile treatment remained stable, although, like
      insecure adolescents, they remembered the conflicts as being less positive than
      initially reported.

PMID- 22390660
TI  - Dopaminergic modulation of incentive motivation in adolescence: age-related
      changes in signaling, individual differences, and implications for the
      development of self-regulation.
AB  - Behavioral activation that is associated with incentive-reward motivation
      increases in adolescence relative to childhood and adulthood. This quadratic
      developmental pattern is generally supported by behavioral and experimental
      neuroscience findings. It is suggested that a focus on changes in dopamine
      neurotransmission is informative in understanding the mechanism for this
      adolescent increase in reward-related behavioral activation and subsequent
      decline into adulthood. Evidence is presented to indicate that incentive-reward
      motivation is modulated by mesoaccumbens dopamine, and that it increases in
      adolescence before declining into adulthood because of normative developmental
      changes at the molecular level. Potential mechanisms of variation in functional
      mesoaccumbens dopamine transmission are discussed with a focus on the interplay
      between tonic and phasic modes of dopamine transmission in modulating both
      general incentive-motivational biases and the efficacy of reward learning during
      exposure to novel reward experiences. Interactions between individual difference
      factors and these age-related trends are discussed.

PMID- 22390663
TI  - Disagreement and causal learning: others' hypotheses affect children's
      evaluations of evidence.
AB  - When children evaluate evidence and make causal inferences, they are sensitive to
      the social context in which data are generated. This study investigated whether
      children learn more from evidence generated by an agent who agrees with them or
      from one who disagrees with them. Children in two age groups (5- and 6-year-olds
      and 9- and 10-year-olds) observed the functioning of a machine that lit up and
      played music in the presence of certain objects. After endorsing one of two
      plausible causal hypotheses, children observed a puppet either agree or disagree
      with their own hypotheses. The puppet then generated a further piece of evidence
      that confirmed, disconfirmed, or was neutral with respect to the children's
      hypotheses. When they were later asked to make causal inferences about objects
      they did not directly observe, children in both age groups responded
      differentially to identical evidence depending on whether the agent agreed or
      disagreed, and they often drew stronger inferences in response to disagreement.
      In addition, older children were particularly sensitive to disagreement when the
      evidence was ambiguous. Our results suggest that children consider the
      relationship between their own and others' hypotheses when evaluating evidence
      that others generate.

PMID- 22390662
TI  - Longitudinal changes in behavioral approach system sensitivity and brain
      structures involved in reward processing during adolescence.
AB  - Figure 2 was distorted in production. The correct version is presented in the
      erratum.] Adolescence is a period of radical normative changes and increased risk
      for substance use, mood disorders, and physical injury. Researchers have proposed
      that increases in reward sensitivity (i.e., sensitivity of the behavioral
      approach system [BAS]) and/or increases in reactivity to all emotional stimuli
      (i.e., reward and threat sensitivities) lead to these phenomena. The present
      study is the first longitudinal investigation of changes in reward (i.e., BAS)
      sensitivity in 9- to 23-year-olds across a 2-year follow-up. Support was found
      for increased reward sensitivity from early to late adolescence, and evidence was
      found for decline in the early 20s. This decline is combined with a decrease in
      left nucleus accumbens (Nacc) volume, a key structure for reward processing, from
      the late teens into the early 20s. Furthermore, we found longitudinal increases
      in sensitivity to reward to be predicted by individual differences in the Nacc
      and medial orbitofrontal cortex (OFC) volumes at baseline in this developmental
      sample. Similarly, increases in sensitivity to threat (i.e., behavioral
      inhibition system sensitivity) were qualified by sex, with only females
      participants experiencing this increase, and predicted by individual differences
      in lateral OFC volumes at baseline.

PMID- 22390664
TI  - What infants know and what they do: perceiving possibilities for walking through
      openings.
AB  - What infants decide to do does not necessarily reflect the extent of what they
      know. In the current study, 17-month-olds were encouraged to walk through
      openings of varying width under risk of entrapment. Infants erred by squeezing
      into openings that were too small and became stuck, suggesting that they did not
      accurately perceive whether they could fit. However, a second penalty condition
      revealed accurate action selection when errors resulted in falling, indicating
      that infants are indeed perceptually sensitive to fitting through openings.
      Furthermore, independent measures of perception were equivalent between the two
      penalty conditions, suggesting that differences in action selection resulted from
      different penalties, not lack of perceptual sensitivity.

PMID- 22390665
TI  - Charting the Eccles' expectancy-value model from mothers' beliefs in childhood to
      youths' activities in adolescence.
AB  - The Eccles' expectancy-value model posits that a cascade of mechanisms explain
      associations between parents' beliefs and youths' achievement-related behaviors.
      Specifically, parents' beliefs predict parents' behaviors; in turn, parents'
      behaviors predict youths' motivational beliefs, and youths' motivational beliefs
      predict their behaviors. This investigation focused on testing this model with
      mothers in sports, music, math, and reading over a 12-year period. Data were
      drawn from mother, youth, and teacher questionnaires collected as part of
      Childhood and Beyond Study (92% European American; N = 723). Mothers' beliefs in
      sports, music, and math positively predicted their behaviors in these areas 1
      year later, which predicted youths' self-concepts of ability and values (i.e.,
      their motivational beliefs) in these domains 1 year later. Adolescents'
      motivational beliefs predicted time spent in organized sport activities, playing
      music, and reading after school measured 4 years later as well as the number of
      math courses taken in high school. Furthermore, except in reading, mothers'
      behaviors mediated the relations between mothers' and youths' beliefs, and
      youths' beliefs mediated the relations between mothers' behaviors and youths'
      behaviors. Although there were mean-level differences in several indicators based
      on child gender, in most cases the relations among these indicators did not
      significantly vary by child gender. This study highlights the processes by which
      mothers' beliefs during their children's childhood can predict children's
      activities in adolescence.

PMID- 22390666
TI  - Marijuana use and risky sexual behavior among high-risk adolescents:
      trajectories, risk factors, and event-level relationships.
AB  - Adolescents involved with the juvenile justice system have a high incidence of
      risky sexual behaviors resulting in unintended pregnancy and sexually transmitted
      infections. Substance use may be particularly important as a risk factor for
      unsafe sexual behavior for this group, and recent evidence suggests a possible
      association between marijuana use and risky sexual behavior. Adolescents (n =
      728; 33% female) on probation were followed for 2 years, at intervals of 6
      months, to explore the association of marijuana use and condom use longitudinally
      and at a specific intercourse occasion. Latent growth curve modeling indicated
      that greater marijuana use at baseline was associated with a steeper decline in
      condom use over the 2-year period of the study. In-depth analysis of the most
      recent intercourse occasion suggested that condom use was less likely if
      marijuana was being used by the participant or his/her partner and that this
      association was more pronounced if intercourse occurred with someone the
      participant had just met. Implications for the prevention of risky sexual
      behavior in this population are discussed.

PMID- 22390667
TI  - Educational and career interests in math: a longitudinal examination of the links
      between classroom environment, motivational beliefs, and interests.
AB  - Drawing on the expectancy-value model, stage-environment fit theory, and self
      determination theory, this study examined the longitudinal associations between
      classroom characteristics, expectancies-values, high school course enrollment,
      and career aspirations in the domain of math. Data were collected on 3,048 youth
      who reported on their classroom experiences in 7th grade, expectancies-values in
      6th, 7th, and 10th grades, and career aspirations in 12th grade. Student grades
      for math courses were collected from school records at 6th, 7th, and 10th grades,
      and their math course enrollment was collected from 9th through 12th grades.
      Results indicated that students' math classroom experiences predicted their
      expectancies and values, which, in turn, predicted the number of high school math
      courses taken and career aspirations in math. Gender and math ability differences
      are also discussed.

PMID- 22390668
TI  - Difference or disorder? Cultural issues in understanding neurodevelopmental
      disorders.
AB  - Developmental disorders, such as autism spectrum disorder and specific language
      impairment, are biologically based disorders that currently rely on behaviorally
      defined criteria for diagnosis and treatment. Specific behaviors that are
      included in diagnostic frameworks and the point at which individual differences
      in behavior constitute abnormality are largely arbitrary decisions. Such
      decisions are therefore likely to be strongly influenced by cultural values and
      expectations. This is evident in the dramatically different prevalence rates of
      autism spectrum disorder across countries and across different ethnic groups
      within the same country. In this article, we critically evaluate the
      understanding of developmental disorders from a cultural perspective. We
      specifically consider the challenges of applying diagnostic methods across
      cultural contexts, the influence of cultural values and expectations on the
      identification and treatment of children with suspected disorders, and how cross
      cultural studies can help to refine cognitive theories of disorder that have been
      derived exclusively from Western North American and European investigations. Our
      review synthesizes clinical, cultural, and theoretical work in this area,
      highlighting potential universals of disorder and concluding with recommendations
      for future research and practice.

PMID- 22390670
TI  - Understanding infants' and children's social learning about foods: previous
      research and new prospects.
AB  - Developmental psychologists have devoted significant attention to investigating
      how children learn from others' actions, emotions, and testimony. Yet most of
      this research has examined children's socially guided learning about artifacts.
      The present article focuses on a domain that has received limited attention from
      those interested in the development of social cognition: food. We begin by
      reviewing the available literature on infants' and children's development in the
      food domain and identify situations in which children evidence both successes and
      failures in their interactions with foods. We focus specifically on the role that
      other people play in guiding what children eat and argue that understanding
      patterns of successes and failures in the food domain requires an appreciation of
      eating as a social phenomenon. We next propose a series of questions for future
      research and suggest that examining food selection as a social phenomenon can
      shed light on mechanisms underlying children's learning from others and provide
      ideas for promoting healthy social relationships and eating behaviors early in
      development.

PMID- 22390669
TI  - Interaction between serotonin transporter polymorphism (5-HTTLPR) and stressful
      life events in adolescents' trajectories of anxious/depressed symptoms.
AB  - Caspi et al. (2003) found an interaction between the serotonin transporter
      polymorphism gene (5-HTTLPR) and stressful life events on depression. Subsequent
      attempts to replicate have been inconsistent. The present research included long
      allele variants modified by SNP rs25531 and tested the interaction on
      adolescents' trajectories of anxious/depressed symptoms, with consideration of
      possible age effects. Adolescents (N = 574), of whom 436 were genotyped, were
      followed from ages 12 to 17. Analyses demonstrated a G * E interaction in
      predicting the development of anxious/depressed symptoms. Specifically,
      adolescents with lower serotonin transcriptional efficiency (TE) genotypes whose
      mothers reported more stressful events were reported to show more
      anxious/depressed symptoms and greater increases in the development of symptoms
      of anxiety and depression than were higher TE adolescents, particularly at ages
      16 and 17. Interactions did not differ by gender. Findings demonstrate that
      stress may affect adolescents' likelihood of experiencing anxious/depressed
      symptoms when they have a low serotonin TE (A/G-modified 5-HTTLPR) genotype and
      suggest that the vulnerability may be stronger in late than early adolescence.

PMID- 22390671
TI  - A propensity score matching study of participation in community activities: a
      path to positive outcomes for youth in New Zealand?
AB  - Extracurricular activities are important in many young people's lives and have
      been associated with positive academic, psychological, and social outcomes.
      However, most previous research has been limited to school-based activities in
      the North American context. This study expands existing literature by analyzing
      longitudinal data from more than 1,300 young Maori and European New Zealanders,
      using propensity score matching techniques to control for selection effects.
      Results suggest that youth participating in community-based activities
      experienced greater social support than nonparticipants. For Maori youth,
      participating in nonsports activities was associated with later benefits, while
      for New Zealand European youth, benefits were associated with sports activities.
      Participants of different ages reported different types of benefits. These
      findings highlight points of similarity and difference between New Zealand and
      North American youth and provide a better understanding of the positive impacts
      of community-based activities for young people.

PMID- 22390673
TI  - System-wide emissions implications of increased wind power penetration.
AB  - This paper discusses the environmental effects of incorporating wind energy into
      the electric power system. We present a detailed emissions analysis based on
      comprehensive modeling of power system operations with unit commitment and
      economic dispatch for different wind penetration levels. First, by minimizing
      cost, the unit commitment model decides which thermal power plants will be
      utilized based on a wind power forecast, and then, the economic dispatch model
      dictates the level of production for each unit as a function of the realized wind
      power generation. Finally, knowing the power production from each power plant,
      the emissions are calculated. The emissions model incorporates the effects of
      both cycling and start-ups of thermal power plants in analyzing emissions from an
      electric power system with increasing levels of wind power. Our results for the
      power system in the state of Illinois show significant emissions effects from
      increased cycling and particularly start-ups of thermal power plants. However, we
      conclude that as the wind power penetration increases, pollutant emissions
      decrease overall due to the replacement of fossil fuels.

PMID- 22390672
TI  - Overexpression of SlSOS2 (SlCIPK24) confers salt tolerance to transgenic tomato.
AB  - The Ca(2+)-dependent SOS pathway has emerged as a key mechanism in the
      homeostasis of Na(+) and K(+) under saline conditions. We have identified and
      functionally characterized the gene encoding the calcineurin-interacting protein
      kinase of the SOS pathway in tomato, SlSOS2. On the basis of protein sequence
      similarity and complementation studies in yeast and Arabidopsis, it can be
      concluded that SlSOS2 is the functional tomato homolog of Arabidopsis AtSOS2 and
      that SlSOS2 operates in a tomato SOS signal transduction pathway. The
      biotechnological potential of SlSOS2 to provide salt tolerance was evaluated by
      gene overexpression in tomato (Solanum lycopersicum L. cv. MicroTom). The better
      salt tolerance of transgenic plants relative to non-transformed tomato was shown
      by their faster relative growth rate, earlier flowering and higher fruit
      production when grown with NaCl. The increased salinity tolerance of SlSOS2
      overexpressing plants was associated with higher sodium content in stems and
      leaves and with the induction and up-regulation of the plasma membrane Na(+)/H(+)
      (SlSOS1) and endosomal-vacuolar K(+), Na(+)/H(+) (LeNHX2 and LeNHX4) antiporters,
      responsible for Na(+) extrusion out of the root, active loading of Na(+) into the
      xylem, and Na(+) and K(+) compartmentalization.

PMID- 22390674
TI  - Follow-up study of vitiligo patients treated with autologous epidermal sheet
      transplants.
AB  - BACKGROUND: Autologous epidermal transplantation is available for the treatment
      of stable vitiligo. However, the results of this technique are affected by many
      factors. OBJECTIVES: It is important to investigate the long-term results and
      factors that might influence the outcome of the autologous epidermal grafting
      technique to form a basis for guidance for patients with vitiligo. METHODS: We
      performed a follow-up study involving 173 patients (95 male, 78 female) with
      vitiligo vulgaris and 109 patients (59 male, 50 female) with segmental vitiligo
      who underwent autologous epidermal grafting. We investigated the long-term
      percentage of repigmentation and colour matching up to 13 years after treatment
      (mean 1.87 years). RESULTS: The mean percentage of repigmentation in the total of
      1938 sheets was 80.65%. In patients with vitiligo vulgaris, 110 (63.6%) showed
      excellent repigmentation, 18 (10.4%) showed good, 4 (5.8%) showed fair and 12
      (20.2%) showed poor repigmentation. In patients with segmental vitiligo, 83 (76%)
      showed excellent repigmentation, 10 (9%) showed good, 4 (4%) showed fair and 12
      (11%) showed poor repigmentation. In segmental vitiligo, the degree of
      repigmentation was significantly higher than that in vitiligo vulgaris lesions.
      Better outcomes were obtained in female patients and less than 20 years old
      patients, whereas results in male patients and more than 20 years old were
      inferior in both vitiligo vulgaris and segmental vitiligo patients. The face and
      neck had a higher completely matching ratio in the treated area with the
      surrounding skin compared to the non-exposed sites. However, the face and neck
      had a lower repigmentation in vitiligo vulgaris. There was a higher ratio of
      Koebner phenomenon on the donor site and new lesions on the other sites in 45 no
      repigmentation patients. CONCLUSIONS: Autologous epidermal transplantation
      achieves a high percentage of repigmentation which is affected by sex, age,
      types, position, duration and the stability time before transplantation in
      vitiligo patients. A more perfect colour matching was obtained in exposure sites.
      Disease activity after transplantation was very important for repigmentation or
      not.

PMID- 22390675
TI  - Measuring markers of liver function using a micropatterned paper device designed
      for blood from a fingerstick.
AB  - This paper describes a paper-based microfluidic device that measures two
      enzymatic markers of liver function (alkaline phosphatase, ALP, and aspartate
      aminotransferase, AST) and total serum protein. A device consists of four
      components: (i) a top plastic sheet, (ii) a filter membrane, (iii) a patterned
      paper chip containing the reagents necessary for analysis, and (iv) a bottom
      plastic sheet. The device performs both the sample preparation (separating blood
      plasma from erythrocytes) and the assays; it also enables both qualitative and
      quantitative analysis of data. The data obtained from the paper-microfluidic
      devices show standard deviations in calibration runs and "spiked" standards that
      are acceptable for routine clinical use. This device illustrates a type of test
      useable for a range of assays in resource-poor settings.

PMID- 22390676
TI  - Angled-predrilling depth and mini-implant shape effects on the mechanical
      properties of self-drilling orthodontic mini-implants during the angled insertion
      procedure.
AB  - OBJECTIVE: To investigate the effects of orthodontic mini-implant (OMI) shape and
      angled-predrilling depth on the mechanical properties of OMIs during the angled
      insertion procedure. MATERIALS AND METHODS: A total of 30 OMIs (self-drilling
      type, 7 mm in length) were allocated into six groups according to the OMI shape
      (cylindrical or tapered) and angled-predrilling depth (control, 1.5-mm and 4.0-mm
      angled-predrilling; predrilled with 1-mm-diameter drill-bit), as follows: C-con,
      C-1.5, C-4.0, T-con, T-1.5, and T-4.0 groups (N  =  5 per group). The OMIs were
      installed at an angle of 60 degrees  in double-layer artificial bone blocks that
      simulated the cortical and cancellous bone (Sawbone((r))). Total insertion time
      (TIT), maximum insertion torque (MIT), total insertion energy (TIE), and
      inclination of the time-torque graph (INC) were measured. RESULTS: Within the
      same shape group, angled-predrilling had a shorter TIT than did the control
      (control vs 1.5; control vs 4.0; all P < .05). MIT and TIE decreased in the order
      of control, 1.5-mm, and 4.0-mm angled-predrilling (control vs 1.5; 1.5 vs 4.0;
      all P < .05), but INC increased from control to 1.5-mm angled-predrilling and
      decreased from 1.5-mm to 4.0-mm angled-predrilling within the same shape group
      (control vs 1.5, 1.5 vs 4.0; all P < .05). The MIT of the tapered group was
      greater than that of the cylindrical group (C-con vs T-con, C-1.5 vs T-1.5; all P
      < .05, C-4.0 vs T-4.0; P < .01). In the same angled-predrilling depth, no
      differences were observed in TIE between the cylindrical and tapered groups (C
      1.5 vs T-1.5, C-4.0 vs T-4.0; all P > .05). CONCLUSIONS: In angled-predrilling
      insertion of OMIs into thick cortical bone, tapered OMIs might be a better choice
      than cylindrical OMIs for increasing primary stability because of higher MIT and
      similar TIE values.

PMID- 22390678
TI  - New prognostic markers, determined using gene expression analyses, reveal two
      distinct subtypes of chronic myelomonocytic leukaemia patients.
AB  - Chronic myelomonocytic leukaemia (CMML) is a heterogeneous haematopoietic
      disorder characterized by myeloproliferative or myelodysplastic features. At
      present, the pathogenesis of this malignancy is not completely understood. In
      this study, we sought to analyse gene expression profiles of CMML in order to
      characterize new molecular outcome predictors. A learning set of 32 untreated
      CMML patients at diagnosis was available for TaqMan low-density array gene
      expression analysis. From 93 selected genes related to cancer and cell cycle, we
      built a five-gene prognostic index after multiplicity correction. Using this
      index, we characterized two categories of patients with distinct overall survival
      (94% vs. 19% for good and poor overall survival, respectively; P = 0.007) and we
      successfully validated its strength on an independent cohort of 21 CMML patients
      with Affymetrix gene expression data. We found no specific patterns of
      association with traditional prognostic stratification parameters in the learning
      cohort. However, the poor survival group strongly correlated with high-risk
      treated patients and transformation to acute myeloid leukaemia. We report here a
      new multigene prognostic index for CMML, independent of the gene expression
      measurement method, which could be used as a powerful tool to predict clinical
      outcome and help physicians to evaluate criteria for treatments.

PMID- 22390679
TI  - A common variant near TERC and telomere length are associated with susceptibility
      to childhood acute lymphoblastic leukemia in Chinese.
AB  - Telomeres are involved in maintaining chromosomal stability, cellular immortality
      and tumorigenesis. A recent genome-wide association study has identified an
      association between telomere length and two common variants (rs12696304 and
      rs16847897) at 3q26 that includes TERC. We hypothesized that the two variants and
      relative telomere length (RTL) would be predictors of the risk of childhood acute
      lymphoblastic leukemia (ALL). A case-control study of 570 cases and 673 cancer
      free controls among Chinese children was performed. We found that there was a
      protective relationship between the second and third quartiles of RTL and risk of
      ALL [adjusted odds ratio (OR) with 95% confidence interval (95% CI) by quartile:
      0.65 (0.47-0.91), 0.56 (0.40-0.79)], compared with the first quartile (shortest)
      RTL. Moreover, rs16847897 CG genotype increased the risk of childhood ALL by 29%
      compared with the CC genotype. Our findings indicate that extreme telomere length
      may be a potential predictor for future risk of ALL, and TERC rs16847897 may
      contribute to the development of childhood ALL.

PMID- 22390677
TI  - A randomized controlled trial investigating the effect of Pycnogenol and Bacopa
      CDRI08 herbal medicines on cognitive, cardiovascular, and biochemical functioning
      in cognitively healthy elderly people: the Australian Research Council Longevity
      Intervention (ARCLI) study protocol (ANZCTR12611000487910).
AB  - BACKGROUND: One of the major challenges associated with our ageing population is
      the increasing incidence of age-associated cognitive decline, which has
      significant implications for an individual's ability to lead a productive and
      fulfilling life. In pure economic terms the costs of ageing reflects decreased
      productivity and engagement with the workforce. The maintenance of brain health
      underpinning intact cognition is a key factor to maintaining a positive, engaged,
      and productive lifestyle. In light of this, the role of diet, including
      supplementation with nutritional and even pharmacological interventions capable
      of ameliorating the neurocognitive changes that occur with age constitute vital
      areas of research. METHODS: In order to reduce cognitive ageing, the ARC
      longevity intervention (ARCLI) was developed to examine the effects of two
      promising natural pharmacologically active supplements on cognitive performance.
      ARCLI is a randomized, placebo-controlled, double-blind, 3-arm clinical trial in
      which 465 participants will be randomized to receive an extract of Bacopa
      monnieri (CDRI08 300 mg/day), Pycnogenol (150 mg/day), or placebo daily for 12
      months. Participants will be tested at baseline and then at 3, 6 and 12 months
      post-randomization on a wide battery of cognitive, neuropsychological and mood
      measures, cardiovascular (brachial and aortic systolic and diastolic blood
      pressures as well as arterial stiffness), biochemical (assays to measure
      inflammation, oxidative stress and safety) as well as genetic assessments
      (telomere length and several Single Nucleotide Polymorphisms). The primary aim is
      to investigate the effects of these supplements on cognitive performance. The
      secondary aims are to explore the time-course of cognitive enhancement as well as
      potential cardiovascular and biochemical mechanisms underpinning cognitive
      enhancement over the 12 months of administration.ARCLI will represent one of the
      largest and most comprehensive experimental clinical trials in which supplements
      are administered to elderly participants. Results from ARCLI may help develop
      novel preventative health practices and nutritional/pharmacological targets in
      the elderly for cognitive and brain health. TRIAL REGISTRATION: Australia and New
      Zealand Clinical Trials Register (ANZCTR): ACTRN12611000487910.

PMID- 22390682
TI  - Robot-assisted laparoscopic prostatectomy versus open: comparison of the learning
      curve of a single surgeon.
AB  - BACKGROUND AND PURPOSE: Because of the increased use of robot-assisted
      laparoscopic prostatectomy (RALP) for the management of localized prostate
      cancer, surgeons in training face the issues of developing skills in both open
      surgery and the robotic console. This study compares prospectively the safety and
      efficacy of the first 50 open radical retropubic prostatectomy (RRP) procedures
      and the first 50 RALP procedures, performed by the same surgeon in the same
      institution. PATIENTS AND METHODS: The patients' baseline demographic, clinical,
      and oncologic parameters were prospectively recorded. The study end points
      included oncologic outcome, functional outcomes (at 3 months), and perioperative
      parameters. Complications were classified according to the modified Clavien
      system. RESULTS: No statistically significant differences were noted between the
      two groups in terms of preoperative patient characteristics and oncologic
      parameters. The operative time and mean estimated blood loss were lower in the
      RALP group (P<0.001), but no statistically significant difference was noted in
      regard to transfusion rates (P=0.362). Mean hospital stay was lower in the RALP
      group (P<0.001). The minor (Clavien I+II) and major (Clavien III+IV) complication
      rates were comparable between the two groups. The overall positive margin (PSM)
      rates were 20% and 18% for RRP and RALP, respectively (P=0.799), while for pT(3)
      disease, the PSM rates were 26.1% and 22.2%% for RRP and RALP, respectively
      (P=0.53). The 3-month continence rates were 88% and 90% for RRP and RALP,
      respectively (P=0.749). For preoperatively potent patients, 3-month potency rates
      were comparable between the two groups (60.6% and 62.1% in the RRP and the RALP
      group, respectively, P=0.893). CONCLUSION: The early learning curve for RALP
      appears safe and results in equivalent functional and oncologic outcome, when
      compared with the results of open surgery.

PMID- 22390680
TI  - Risk factors for cardiovascular mortality in patients with systemic lupus
      erythematosus, a prospective cohort study.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease.
      Cardiovascular disease (CVD) is common and a major cause of mortality. Studies on
      cardiovascular morbidity are abundant, whereas mortality studies focusing on
      cardiovascular outcomes are scarce. The aim of this study was to investigate
      causes of death and baseline predictors of overall (OM), non-vascular (N-VM), and
      specifically cardiovascular (CVM) mortality in SLE, and to evaluate systematic
      coronary risk evaluation (SCORE). METHODS: 208 SLE patients were included 1995
      1999 and followed up after 12 years. Clinical evaluation, CVD risk factors, and
      biomarkers were recorded at inclusion. Death certificates and autopsy protocols
      were collected. Causes of death were divided into CVM (ischemic vascular and
      general atherosclerotic diseases), N-VM and death due to pulmonary hypertension.
      Predictors of mortality were investigated using multivariable Cox regression.
      SCORE and standardized mortality ratio (SMR) were calculated. RESULTS: During
      follow-up 42 patients died at mean age of 62 years. SMR 2.4 (CI 1.7-3.0). 48% of
      deaths were caused by CVM. SCORE underestimated CVM but not to a significant
      level. Age, high cystatin C levels and established arterial disease were the
      strongest predictors for all- cause mortality. After adjusting for these in
      multivariable analyses, only smoking among traditional risk factors, and high
      soluble vascular cell adhesion molecule-1 (sVCAM-1), high sensitivity C-reactive
      protein (hsCRP), anti-beta2 glycoprotein-1 (abeta2GP1) and any antiphospholipid
      antibody (aPL) among biomarkers, remained predictive of CVM. CONCLUSION: With the
      exception of smoking, traditional risk factors do not capture the main underlying
      risk factors for CVM in SLE. Rather, cystatin C levels, inflammatory and
      endothelial markers, and antiphospholipid antibodies (aPL) differentiate patients
      with favorable versus severe cardiovascular prognosis. Our results suggest that
      these new biomarkers are useful in evaluating the future risk of cardiovascular
      mortality in SLE patients.

PMID- 22390684
TI  - Pulmonary hypertension and pregnancy--a review of 12 pregnancies in nine women.
AB  - OBJECTIVE: To report outcomes in a recent series of pregnancies in women with
      pulmonary hypertension (PH). DESIGN: Retrospective case note review. SETTING:
      Tertiary referral unit (Chelsea and Westminster and Royal Brompton Hospitals).
      SAMPLE: Twelve pregnancies in nine women with PH between 1995 and 2010. METHODS:
      Multidisciplinary review of case records. MAIN OUTCOME MEASURES: Maternal and
      neonatal mortality and morbidity. RESULTS: There were two maternal deaths (1995
      and 1998), one related to pre-eclampsia and one to arrhythmia. Maternal morbidity
      included postpartum haemorrhage (five cases), and one post-caesarean evacuation
      of a wound haematoma. There were no perinatal deaths, nine live births and three
      first-trimester miscarriages. Mean birthweight was 2197 g, mean gestational age
      was 34 weeks (range 26-39), and mean birthweight centile was 36 (range 5-60).
      Five babies required admission to the neonatal intensive care unit, but were all
      eventually discharged home. All women were delivered by caesarean section (seven
      elective and two emergency deliveries), under general anaesthetic except for one
      emergency and one elective caesarean performed under regional block. CONCLUSIONS:
      Maternal and fetal outcomes for women with PH may be improving. However, the risk
      of maternal mortality remains significant, so that early and effective
      counselling about contraceptive options and pregnancy risks should continue to
      play a major role in the management of such women when they reach reproductive
      maturity.

PMID- 22390685
TI  - Tailoring of Seebeck coefficient with surface roughness effects in silicon sub-50
      nm films.
AB  - The effect of surface roughness on the Seebeck coefficient in the sub-50-nm scale
      silicon ultra thin films is investigated theoretically using nonequilibrium
      Green's function formalism. For systematic studies, the surface roughness is
      modelled by varying thickness periodically with square wave profile characterized
      by two parameters: amplitude (A 0) and wavelength (lambda). Since high Seebeck
      coefficient is obtained if the temperature difference between the ends of device
      produces higher currents and higher induced voltages, we investigate how the
      generated current and induced voltage is affected with increasing A 0 and lambda.
      The theoretical investigations show that pseudoperiodicity of the device
      structure gives rise to two effects: firstly the threshold energy at which the
      transmission of current starts is shifted towards higher energy sides and
      secondly transmission spectra of current possess pseudobands and pseudogaps. The
      width of the pseudobands and their occupancies determine the total generated
      current. It is found that current decreases with increasing A 0 but shows a
      complicated trend with lambda. The trends of threshold energy determine the
      trends of Seebeck voltage with roughness parameters. The increase in threshold
      energy makes the current flow in higher energy levels. Thus, the Seebeck voltage,
      i.e. voltage required to nullify this current, increases. Increase in Seebeck
      voltage results in increase in Seebeck coefficient. We find that threshold energy
      increases with increasing A 0 and frequency (1/lambda). Hence, Seebeck voltage
      and Seebeck coefficient increase vice versa. It is observed that Seebeck
      coefficient is tuneable with surface roughness parameters. 

PMID- 22390683
TI  - A variable light domain fluorogen activating protein homodimerizes to activate
      dimethylindole red.
AB  - Novel fluorescent tools such as green fluorescent protein analogues and fluorogen
      activating proteins (FAPs) are useful in biological imaging for tracking protein
      dynamics in real time with a low fluorescence background. FAPs are single-chain
      variable fragments (scFvs) selected from a yeast surface display library that
      produce fluorescence upon binding a specific dye or fluorogen that is normally
      not fluorescent when present in solution. FAPs generally consist of human
      immunoglobulin variable heavy (V(H)) and variable light (V(L)) domains covalently
      attached via a glycine- and serine-rich linker. Previously, we determined that
      the yeast surface clone, V(H)-V(L) M8, could bind and activate the fluorogen
      dimethylindole red (DIR) but that the fluorogen activation properties were
      localized to the M8V(L) domain. We report here that both nuclear magnetic
      resonance and X-ray diffraction methods indicate the M8V(L) forms noncovalent,
      antiparallel homodimers that are the fluorogen activating species. The M8V(L)
      homodimers activate DIR by restriction of internal rotation of the bound dye.
      These structural results, together with directed evolution experiments with both
      V(H)-V(L) M8 and M8V(L), led us to rationally design tandem, covalent homodimers
      of M8V(L) domains joined by a flexible linker that have a high affinity for DIR
      and good quantum yields.

PMID- 22390686
TI  - Patients with psoriasis and atopic dermatitis show distinct anxiety profiles.

PMID- 22390687
TI  - Common transcriptional effects in the mouse striatum following chronic treatment
      with heroin and methamphetamine.
AB  - The molecular alterations that underlie the long-lasting behavioural effects of
      drugs of abuse, such as psychomotor sensitization and physical dependence, are
      still not known. Moreover, it is not known which molecular effects are similar
      for addictive drugs from various pharmacological classes. In this study, we
      utilized whole-genome microarray profiling to evaluate the detailed time-course
      of transcriptional alterations in the mouse striatum during chronic treatment
      with heroin (HER) and methamphetamine (METH) and after period of spontaneous
      withdrawal. We identified 27 genes regulated by chronic drug administration. The
      overlap between lists of HER- and METH-induced genes was highly significant. The
      most substantial impact on the gene expression profile was observed for circadian
      genes (Per1, Per2 and Nr1d1). However, changing the treatment scheme from diurnal
      to nocturnal was sufficient to attenuate the drug-induced changes in circadian
      gene mRNA levels. Both of the drugs caused a dose-dependent induction in
      glucocorticoid-dependent genes with relatively long mRNA half-lives (Fkbp5,
      Sult1a1 and Plin4). The analysis also showed a drug-regulated group of
      transcripts enriched in the nucleus accumbens and includes well known (Pdyn,
      Cartpt and Rgs2) as well as new (Fam40b and Inmt) candidate genes. All identified
      alterations in the striatal transcriptome were transient and persisted up to 6
      days after withdrawal. Behavioural sensitization, however, was maintained
      throughout the 12-day withdrawal period for both HER and METH. We suggest that
      transient gene expression alterations during drug treatment and in the early
      period of withdrawal are involved in the establishment of persistent neuroplastic
      alterations responsible for the development of drug addiction.

PMID- 22390689
TI  - Editorial: modulation and new mediators in inflammation.

PMID- 22390688
TI  - Investigator-initiated, open-label trial of ustekinumab for the treatment of
      moderate-to-severe palmoplantar psoriasis.
AB  - BACKGROUND: Palmoplantar psoriasis is a variant of psoriasis resistant to many
      forms of treatment. METHODS: Twenty subjects with moderate-to-severe psoriasis of
      the palms and soles, 50% with pustules at baseline, were treated with ustekinumab
      at weeks 0, 4, and 16. All subjects had previously failed topical
      corticosteroids. Dosing was 45 mg subcutaneously for subjects weighing <100 kg
      and 90 mg for subjects weighing >=100 kg. The primary endpoint was the percent of
      subjects achieving clinical clearance at week 16, defined as Palm-Sole
      Physician's Global Assessment <=1. The study received Tufts Medical Center IRB
      approval. RESULTS: After 16 weeks of treatment, 35% (7/20) of subjects achieved
      clinical clearance. Sixty percent (12/20) improved two or more points on the Palm
      Sole Physician's Global Assessment scale. Sixty-seven percent (6/9) of those
      receiving the 90 mg ustekinumab dose achieved clinical clearance compared with
      nine percent (1/11) receiving 45 mg (p = 0.02). At 24 weeks, mean values showed
      56% improvement in Dermatology Life Quality Index, and 34% improvement in pain
      Visual Analogue Scale score (all p < 0.05). LIMITATIONS: Assessment tools for
      palmoplantar psoriasis are not yet validated. Five subjects withdrew or were lost
      to follow-up. CONCLUSION: This study demonstrates that ustekinumab dosed at 90 mg
      is effective in controlling signs and symptoms of palmoplantar psoriasis.

PMID- 22390690
TI  - Mast cells in allergic and inflammatory diseases.
AB  - Mast cells are important in the development of allergic and anaphylactic
      reactions, but also in acquired and innate immunity. There is also increasing
      evidence that mast cells participate in inflammatory diseases, where they can be
      activated by non-allergic triggers, such as neuropeptides and cytokines, often
      having synergistic effects as in the case of substance P (SP) and IL-33.
      Secretion of vasoactive mediators, cytokines and proteinases contribute to the
      development of coronary artery disease (CAD), as well as to diet-induced obesity
      and the metabolic syndrome. Mast cells may be able to orchestrate such different
      biological processes through their ability to release pro-inflammatory mediators
      selectively without the degranulation typical of allergic reactions. Recent
      evidence suggests that mitochondrial uncoupling protein 2 (UCP2) and
      mitochondrial translocation regulate mast cell degranulation, but not selective
      mediator release. Better understanding of these two processes and how mast cells
      exert both immunostimulatory and immunosuppressive actions could lead to the
      development of inhibitors of release of specific mediators with novel therapeutic
      applications.

PMID- 22390691
TI  - Immunobiology of antigen-specific immunoglobulin free light chains in chronic
      inflammatory diseases.
AB  - Mast cells are increasingly recognized as critical players in elicitation and
      maintenance of different inflammatory related disorders, like allergy, autoimmune
      diseases and cancer. Mast cells maturate within the tissue and are able to adapt
      to microenvironmental changes. Together with the ability to produce multiple pro-
      and anti-inflammatory mediators upon activation, mast cells are highly capable of
      exerting immunomodulatory functions. Cross-linking of receptor bound IgE is the
      best known mechanism of antigen-specific mast cell activation. In this review we
      focus on a different route of activation, via immunoglobulin free light chains
      (FLCs). Here, we describe current knowledge and concepts on FLCs based on
      preclinical models and data on human subjects, after briefly recapitulating early
      research findings on FLCs. Furthermore, because FLC research mainly focuses on
      mast cells, several mast cell mediated pathologies and mouse models for mast cell
      research will be discussed. Whether targeting of mast cells is beneficial for the
      treatment of specific disorders has to be addressed in future studies. Specific
      inhibition of FLC-mediated mast cell activation may be an interesting avenue to
      treat chronic inflammatory diseases.

PMID- 22390692
TI  - The nervous system as a critical regulator of immune responses underlying
      allergy.
AB  - The nervous and immune systems collaborate in the control of homeostasis and host
      defence. All divisions of the nervous system, sympathetic, parasympathetic and
      sensory, act to regulate immune cell function. Processes under neuronal control
      include antigen processing and presentation, Th1/Th2 balance, immunoglobulin
      production and antigen specific responses, while involvement of the central
      nervous system allows for behavioral changes leading to avoidance of antigen or
      noxious stimuli. It therefore follows that dysregulation of these complex
      bidirectional neuroimmune signaling systems may contribute to the aetiology and
      pathophysiology of immune disorders including atopic disease. A greater
      understanding on how the brain perceives, processes and responds to immune
      challenges and how multiple neurotransmitters interact to maintain or skew the
      balance between tolerance and immunity will undoubtedly provide opportunities for
      the development of novel therapeutics. Furthermore, the implications for atopic
      disease of relatively recent developments such as the cholinergic anti
      inflammatory pathway and the potential direct antigen-specific activation of the
      nervous system require further exploration.

PMID- 22390693
TI  - The mechanism of adjuvanticity of aluminium-containing formulas.
AB  - Vaccinations have been given to people for at least 100 years of which 80 years
      formulated in adjuvants. Currently, aluminium- containing formulas and the oil
      based substance called MF59 are the two adjuvants licensed for clinical use.
      Despite the massive use of aluminium adjuvant, its mechanism of action has been
      only recently addressed. In this review, we will discuss both the cellular and
      molecular mode of action of aluminium-containing adjuvants.

PMID- 22390694
TI  - The pollen enigma: modulation of the allergic immune response by non-allergenic,
      pollen-derived compounds.
AB  - The question what makes an allergen an allergen puzzled generations of
      researchers. Pollen grains of anemophilous plants are the most important allergen
      carriers in ambient air, and pollinosis is a highly prevalent multi-organ disease
      in civilized countries. In the past, research on the allergenicity of pollen has
      mainly focused on elucidating genetic predisposing factors and on defining
      certain structural characteristics of pollen derived allergens. Recently, studies
      extended to the analysis of non-allergenic, adjuvant mediators co-released from
      pollen. Besides active proteases and oxidases, extracts of pollen contain low
      molecular weight molecules like pollen-associated lipid mediators or adenosine
      exhibiting a potential to stimulate and modulate cultured human immune cells.
      This article reviews our current knowledge on non-allergenic, protein and non
      protein compounds from pollen and their in vitro and in vivo effects on the
      allergic immune response. To ultimately judge the physiological relevance of
      these compounds, a systematic approach will be needed comparing their
      releasability, content and activity in different, allergenic and non-allergenic,
      pollen species. System biology such as proteome and metabolome analysis will be a
      useful future approach to better understand pollen biology.

PMID- 22390695
TI  - Inflammasome signaling in pathogenesis of lung diseases.
AB  - Asthma and Chronic Obstructive Pulmonary Disease (COPD) are two important lung
      and airways diseases which affect the lives of ~500 million people worldwide.
      Asthma is a heterogeneous disease that is broadly defined as a clinical syndrome
      characterized by altered lung function, mucus hypersecretion, peribronchial
      inflammation and hyperresponsiveness In contrast, the effect of inhalation of
      toxic particles and gases on the innate and adaptive inflammatory immune systems
      underlie the pathogenesis of COPD. In the last decade, knowledge concerning the
      pathophysiologic mechanisms underlying asthma and COPD has risen tremendously and
      current dogma suggests that the pathogenesis of both diseases is driven by the
      chronic inflammation present in the airways of these patients. Thus,
      understanding the mechanisms for the persistence of inflammation may lead to new
      therapeutic approaches. In this review, we provide an overview of the main signal
      transduction pathways implicated in asthma and COPD pathophysiology focusing on
      inflammasome signaling in various cells types which result in altered
      inflammatory mediator expression.

PMID- 22390696
TI  - Dendritic cells in pathogenesis of COPD.
AB  - COPD (Chronic Obstructive Pulmonary Disease) is an important lung and airway
      disease which affects the lives of around 200 million people worldwide with an
      increasing incidence particularly in developing countries. The pathogenesis of
      COPD is based on the innate and adaptive inflammatory immune response to the
      inhalation of toxic particles and gases. Although cigarette smoking is the
      primary cause of this inflammation, many other environmental and occupational
      exposures contribute to the pathology of COPD. The immune inflammatory changes
      associated with COPD are linked to a tissue repair and remodeling process that
      increases mucus production and causes emphysematous destruction of the gas
      exchanging surface of the lung. The inflamed airways of COPD patients contain
      several inflammatory cells including neutrophils, macrophages, T lymphocytes, and
      dendritic cells (DCs). Little is known about the relative contribution of DCs in
      the pathogenesis of COPD. However the number of DCs is changed in smokers and
      COPD patients and cigarette smoke (CS) induces the release of chemokines from DCs
      that play a role in the pathogenesis of COPD. In this review paper, an overview
      is presented on the role of DCs and their mediators in the pathogenesis of COPD.
      The activation of DCs and their signaling in response to CS will also be
      highlighted and discussed.

PMID- 22390697
TI  - Local inflammation in chronic upper airway disease.
AB  - Chronic Rhinosinusitis (CRS), a chronic upper airway inflammation, is an
      inflammation of the nose and the paranasal cavities and is highly prevalent.
      Chronic rhinosinusitis is currently classified as CRS with nasal polyps or CRS
      without nasal polyps. This review highlights the pathophysiological differences
      in CRS on remodeling and on T-cell patterns. Nasal polyps have a high co
      morbidity with the lower airway inflammatory disease, asthma. Evidence is
      accumulating for the role of superantigens, Staphylococcus aureus enterotoxins,
      in CRS with nasal polyps and asthma, both T helper 2 -biased diseases. Until
      today there are no biomarkers involved in the diagnosis of CRS or the treatment
      follow-up. Further differentiation of the phenotype of the disease is needed,
      which will reflect in the development of new biomarkers and in new innovative
      treatment options. Defining and predicting response to therapy in individual CRS
      patients is a challenge for future research.

PMID- 22390698
TI  - Interleukin-7: a key mediator in T cell-driven autoimmunity, inflammation, and
      tissue destruction.
AB  - IL-7, expressed by stromal cells in primary lymphoid organs, is known for its
      critical role in the development and homeostatic expansion of T cells in humans
      and mice. IL-7 is equally important for B cell development in human and mice, but
      only in mice seems critical for B cell development and expansion. Recent studies
      demonstrate that this potent immunostimulatory cytokine is overexpressed in
      inflamed tissues of patients with (rheumatic) autoimmune diseases and that
      expression levels correlate with clinical parameters of disease. In inflamed
      tissues several cell types, including macrophages, dendritic cells, and
      fibroblasts produce IL-7. IL-7 primarily acts on T cells that abundantly express
      the IL-7 receptor and that are increased at the inflammatory sites, and
      predominantly induces Th1 and Th17-associated cytokine secretion. IL-7-mediated T
      cell-dependent activation of macrophages, dendritic cells and B cells is
      accompanied by up regulation of T cell differentiating factors, chemokines,
      adhesion/co-stimulatory molecules and catabolic cytokines and enzymes. Moreover,
      overexpression of IL-7 is associated with ectopic lymphoid aggregate formation,
      corresponding with the capacity of IL-7 to induce LTbeta and TNFalpha and to
      activate innate lymphoid tissue inducer cells. Additionally, IL-7 promotes T cell
      driven osteoclastogenesis and fibroblast activation, processes involved in tissue
      destruction in chronic inflammation. Altogether this suggests that IL-7 is an
      important proinflammatory mediator in several chronic (rheumatic) inflammatory
      autoimmune diseases. The substantial amelioration of inflammation and
      immunopathology in experimental animal models for these diseases by blocking IL
      7(receptor) supports this role of IL-7 and demonstrates that IL-7 and its
      receptor represent novel targets for immunotherapy.

PMID- 22390699
TI  - Immune cell-derived vesicles: modulators and mediators of inflammation.
AB  - Most cell types can release vesicles. Cell-derived vesicles are increasingly
      recognized as an evolutionary wide-spread mechanism of intercellular
      communication. The paracrine and long range activity of vesicles and their
      regulated cargo-composition endows these vesicles with regulatory properties
      beyond that of the parental cell. The release and biogenesis of cell-derived
      vesicles is a dynamic and tightly controlled process. In the past years it has
      become clear that these vesicles exert a plethora of biological effects. This has
      sparked the intense interest in these vesicles in relation to
      (patho)physiological processes. This review focuses on the role of cell-derived
      vesicles in inflammation, with emphasis on the immune modulating capacity of
      immune cell-derived vesicles. The biological activity of different leukocyte
      derived vesicles is compared, and potential explanations for the strong
      biological effects exhibited by vesicles are provided. The role of cell-derived
      vesicles in inflammatory processes is discussed by speculating how these vesicles
      can contribute to allergic inflammation.

PMID- 22390700
TI  - Difficulties in describing allergic disease modulation by pre-, pro- and
      synbiotics.
AB  - The so-called hygiene hypothesis is, at least in part, accountable for the
      increase in allergic diseases in the developed countries. Although there is
      support for one of its primary predictions that host-microbe interactions in
      early life have longterm effects on the development of disease across
      populations, the theory has already proven to be imperfect as many more recent
      increases in certain diseases cannot be explained by the hygiene hypothesis.
      Nevertheless, many research groups are interested in the host-microbe
      interactions and are exploring the use of "live micro-organisms which, when
      administered in adequate amounts, confer a health benefit to the host"
      (probiotics) and "selectively fermented ingredients that result in specific
      changes, in the composition and/or activity of the gastrointestinal microbiota,
      thus conferring benefit(s) upon host health" (prebiotics) to reduce the allergic
      disease onset or clinical outcomes. As the definitions of pre- and probiotics by
      itself were already adapted after their original dictation, it is not surprising
      that producing generalistic conclusions on the effectiveness of pre-, pro and
      synbiotic intervention in allergic diseases is very challenging as large
      differences exist in used species, methodologies, prebiotic(s) (mixtures) and
      probiotic strains. In this review we elucidate on the hurdles in describing
      prebiotics, probiotics and the combination being synbiotics in allergic
      manifestations.

PMID- 22390701
TI  - Long chain N-3 polyunsaturated fatty acids in the prevention of allergic and
      cardiovascular disease.
AB  - The diet is considered to have a major impact on human health. Dietary lipids
      including long chain polyunsaturated fatty acids (LCPUFA) possess potent
      immunomodulatory activities. Over the last decades the incidence of inflammatory
      disorders including allergic and cardiovascular diseases (CVD) has been rising.
      This phenomenon is associated with deficiencies in N-3 LCPUFA, found in fatty
      fish, and increased content of N-6 LCPUFA in the Western diet. LCPUFA act via
      different mechanisms including membrane fluidity, raft composition, lipid
      mediator formation, signaling pathways and transmembrane receptors. N-3 LCPUFA
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce the
      development of allergic disease by affecting both the innate and adaptive immune
      system involved in the initiation and persistence of allergic disease. Fish oil
      has been shown to be effective in the primary prevention of allergic disease in
      infants at risk when supplemented during pregnancy and lactation. Subtle effects
      of N-3 LCPUFA on the outcome of the immune response may underlie these protective
      effects. This review describes the currently reported effects of LCPUFA on
      dendritic cells, T cells, B cells and mast cells. Also CVD are positively
      affected by N-3 LCPUFA. Populations consuming high amounts of oily fish are
      protected against CVD. Moreover N-3 LCPUFA are effective in the secondary
      prevention of cardiovascular events. Amongst other effects, EPA and DHA have been
      shown to suppress endothelial cell activation hereby reducing adhesion molecule
      expression and endothelial cell - leukocyte interactions. This review describes
      the mechanistic basis of the preventive role for N-3 LCPUFA in allergic disease
      and CVD.

PMID- 22390702
TI  - A nanostructured electrochromic supercapacitor.
AB  - We report the first successful application of an ordered bicontinuous double
      gyroid vanadium pentoxide network in an electrochromic supercapacitor. The
      freestanding vanadia network was fabricated by electrodeposition into a voided
      block copolymer template that had self-assembled into the double-gyroid
      morphology. The highly ordered structure with 11.0 nm wide struts and a high
      specific surface to bulk volume ratio of 161.4 MUm(-1) is ideal for fast and
      efficient lithium ion intercalation/extraction and faradaic surface reactions,
      which are essential for high energy and high power density electrochemical energy
      storage devices. Supercapacitors made from such gyroid-structured vanadia
      electrodes exhibit a high specific capacitance of 155 F g(-1) and show a strong
      electrochromic color change from green/gray to yellow, indicating the capacitor's
      charge condition. The nanostructuring approach and utilizing an electrode
      material that has intrinsic electrochemical color-change properties are concepts
      that can be readily extended to other electrochromic intercalation compounds.

PMID- 22390703
TI  - Focused but fixed: the impact of expectation of external rewards on inhibitory
      control and flexibility in preschoolers.
AB  - Promise of rewards has been widely used in controlling preschoolers' behaviors.
      The current study investigated how the expectation of receiving an external
      reward may influence preschoolers' executive function. Four- to 5-year-old
      Singaporean children were randomly assigned to reward-informed and reward
      uninformed conditions. Results showed that compared with those in the reward
      uninformed condition, although performing the same on the control tasks and
      reporting similar motivation and mood states before being told about the reward,
      the children in the reward-informed condition performed better on the Day/Night
      Stroop (Experiment 1, N = 41) but worse on the Flexible Item Selection Test
      (Experiment 2, N = 43). These findings suggest that the expectation of receiving
      an external reward can influence preschoolers' behavioral control.

PMID- 22390704
TI  - Emotional modulation of visual remapping of touch.
AB  - The perception of tactile stimuli on the face is modulated if subjects
      concurrently observe a face being touched; this effect is termed "visual
      remapping of touch" or the VRT effect. Given the high social value of this
      mechanism, we investigated whether it might be modulated by specific key
      information processed in face-to-face interactions: facial emotional expression.
      In two separate experiments, participants received tactile stimuli, near the
      perceptual threshold, either on their right, left, or both cheeks. Concurrently,
      they watched several blocks of movies depicting a face with a neutral, happy, or
      fearful expression that was touched or just approached by human fingers
      (Experiment 1). Participants were asked to distinguish between unilateral and
      bilateral felt tactile stimulation. Tactile perception was enhanced when viewing
      touch toward a fearful face compared with viewing touch toward the other two
      expressions. In order to test whether this result can be generalized to other
      negative emotions or whether it is a fear-specific effect, we ran a second
      experiment, where participants watched movies of faces-touched or approached by
      fingers-with either a fearful or an angry expression (Experiment 2). In line with
      the first experiment, tactile perception was enhanced when subjects viewed touch
      toward a fearful face and not toward an angry face. Results of the present
      experiments are interpreted in light of different mechanisms underlying different
      emotions recognition, with a specific involvement of the somatosensory system
      when viewing a fearful expression and a resulting fear-specific modulation of the
      VRT effect.

PMID- 22390705
TI  - The Affect Misattribution Procedure: hot or not?
AB  - The Affect Misattribution Procedure (AMP; Payne, Cheng, Govorun, & Stewart, 2005)
      is an important tool in implicit social cognition research, but little is known
      about its underlying mechanisms. This paper investigates whether, as the name
      implies, affect-based processes really underlie the AMP. We used a modified AMP
      that enabled us to separate the influence of affective and nonaffective
      processes. In three studies, evidence for the implication of nonaffective
      processes was consistently found. In contrast, there was no evidence for affect
      based processes. Thus, the AMP rather seems cold than hot. The generalizability
      of the results obtained with the modified AMP is discussed.

PMID- 22390706
TI  - Through the eyes of anxiety: Dissecting threat bias via emotional-binocular
      rivalry.
AB  - An extensive body of research has demonstrated that anxious individuals
      abnormally process threat-related content. Yet, the manner in which clinical
      anxiety affects the selection of threatening signals and their maintenance within
      consciousness is yet to be explored. The present study used an emotional
      binocular rivalry (e-BR) procedure, in which pictures of faces depicting either
      fearful or neutral expressions competed with pictures of a house for conscious
      perception. We assumed that first- or cumulative-preferred perception of faces
      with fearful over neutral expression (i.e., initial or sustained threat bias,
      respectively) stand for preferential selection or maintenance of fear content in
      awareness, correspondingly. Unmedicated patients with social anxiety disorder
      (SAD) and panic disorder (PAD) were compared to healthy controls for threat
      related perceptual biases in the e-BR. At first perception of face, both SAD and
      PAD patients showed a greater initial threat bias than healthy controls. In
      contrast, at cumulative dwell-time of face, patient groups demonstrated a
      diminished sustained threat bias relative to healthy controls, yet in a different
      manner. SAD patients showed a sustained threat bias, though it was smaller than
      in healthy controls. Furthermore, increased levels of reported anxiety among SAD
      patients were associated with enhanced sustained perception of neutral faces. PAD
      patients, on the other hand, showed no sustained threat bias and a diminished
      cumulative perception of fearful faces with increased levels of anxiety traits.
      These findings indicate that anxiety disorders commonly involve an initially
      enhanced selection of threat signals into awareness, followed by disorder
      specific manifestation of diminished preferred maintenance of threat in
      awareness.

PMID- 22390708
TI  - Time-course of attention to negative stimuli: negative affectivity, anxiety, or
      dysphoria?
AB  - Although biased attention to emotional stimuli is considered a vulnerability
      factor for anxiety and dysphoria, research has infrequently related such
      attentional biases to dimensional models of vulnerability for anxiety and mood
      disorders. In two studies (Study 1, n = 64; Study 2, n = 168), we evaluate the
      differential associations of general negative affectivity, anxiety, and dysphoria
      with biases in selective attention among nonclinical participants selected to
      vary in both anxiety and dysphoria. Across both studies, preferential processing
      of angry faces at a 300-ms exposure duration was associated with a general
      tendency to experience a range of negative affect, rather than being specific to
      symptoms of either anxiety or dysphoria. In the second study, we found evidence
      of a suppressor relationship between anxiety and dysphoria in the prediction of
      delayed attentional biases (1,000 ms) for sad faces. In particular, dysphoria was
      specifically associated with biased attention toward sad cues, but only after
      statistically accounting for anxiety; by contrast, anxiety was specifically
      associated with attentional avoidance of sad cues, but only after statistically
      accounting for dysphoria. These results suggest that the specificity of
      relationships between components of negative affectivity and attention to
      emotional stimuli varies as a function of the time course at which attentional
      biases are assessed, highlighting the importance of evaluating both anxiety and
      dysphoria in research on attentional processing of emotional stimuli.

PMID- 22390707
TI  - Influences of parent and child negative emotionality on young children's everyday
      behaviors.
AB  - Negative emotionality is linked to unfavorable life outcomes, but studies have
      yet to examine negative emotionality of parents and children as predictors of
      children's problem behaviors and negative emotion word use in everyday life. This
      study used a novel naturalistic recording device called the Electronically
      Activated Recorder to investigate the separate and interactive influences of
      parent and child negative emotionality on daily child behaviors in a sample of 35
      preschool-aged children over two time points separated by 1 year. Fathers'
      negative emotionality predicted children's whining at Time 1; mothers' negative
      emotionality predicted children's negative emotion word use at Time 1 and
      increases in children's arguing/fighting from Time 1 to Time 2. Parents' ratings
      of child negative emotionality also were associated with increases in children's
      arguing/fighting from Time 1 to Time 2, and child negative emotionality moderated
      the association between mothers' negative emotionality and children's
      arguing/fighting. Further, children with mothers high in negative emotionality
      displayed higher levels of problem behaviors when their mothers self-reported low
      levels of positive emotional expressiveness and/or high levels of negative
      emotional expressiveness. These findings offer preliminary evidence linking
      parent and child negative emotionality to everyday child behaviors and suggest
      that emotional expressiveness may play a key role in moderating the links between
      maternal negative emotionality and child behavioral problems.

PMID- 22390709
TI  - Emotions that associate with uncertainty lead to structured ideation.
AB  - This study tested the role of emotion in structured ideation, a process in which
      newly generated ideas and insights closely follow previously generated ideas and
      insights. Emotions can be differentiated on a number of underlying dimensions,
      including uncertainty, and uncertainty can influence information processing. On
      these grounds, we proposed and tested the idea that (1) emotions that associate
      with appraisals of uncertainty (fear, sadness) lead to more structured ideation
      than emotions that associate with appraisals of certainty (happiness, anger) and
      that (2) appraisals of uncertainty drive this effect. Findings of four
      experiments on idea generation in which (un)certainty was primed (Study 1) and
      emotions were induced through self-generated imagery (Study 2-4) supported these
      predictions.

PMID- 22390710
TI  - Eliciting and maintaining ruminative thought: the role of social-evaluative
      threat.
AB  - This study tested whether a performance stressor characterized by social
      evaluative threat (SET) elicits more rumination than a stressor without this
      explicit evaluative component and whether this difference persists minutes,
      hours, and days later. The mediating role of shame-related cognition and emotion
      (SRCE) was also examined. During a laboratory visit, 144 undergraduates (50%
      female) were randomly assigned to complete a speech stressor in a social
      evaluative threat condition (SET; n = 86), in which an audience was present, or a
      nonexplicit social-evaluative threat condition (ne-SET; n = 58), in which they
      were alone in a room. Participants completed measures of stressor-related
      rumination 10 and 40 min posttask, later that night, and upon returning to the
      laboratory 3-5 days later. SRCE and other emotions experienced during the
      stressor (fear, anger, and sadness) were assessed immediately posttask. As
      hypothesized, the SET speech stressor elicited more rumination than the ne-SET
      speech stressor, and these differences persisted for 3-5 days. SRCE-but not other
      specific negative emotions or general emotional arousal-mediated the effect of
      stressor context on rumination. Stressors characterized by SET may be likely
      candidates for eliciting and maintaining ruminative thought immediately and also
      days later, potentially by eliciting shame-related emotions and cognitions.

PMID- 22390711
TI  - Flexible attention deployment in threatening contexts: an instructed fear
      conditioning study.
AB  - Factors leading humans to shift attention away from danger cues remain poorly
      understood. Two laboratory experiments reported here show that context interacts
      with learning experiences to shape attention avoidance of mild danger cues. The
      first experiment exposed 18 participants to contextual threat of electric shock.
      Attention allocation to mild danger cues was then assessed with the dot-probe
      task. Results showed that contextual threat caused subjects to avert attention
      from danger cues. In the second experiment, 36 participants were conditioned to
      the same contextual threat used in Experiment 1. These subjects then were
      randomly assigned to either an experimental group, trained to shift attention
      toward danger cues, or a placebo group exposed to the same stimuli without the
      training component. As in Experiment 1, contextual threat again caused attention
      allocation away from danger in the control group. However, this did not occur in
      the experimental group. These experiments show that acute contextual threat and
      learning experiences interact to shape the deployment of attention away from
      danger cues.

PMID- 22390713
TI  - Heartwarming memories: Nostalgia maintains physiological comfort.
AB  - Nostalgia, a sentimental longing or wistful affection for the past, is a
      predominantly positive and social emotion. Recent evidence suggests that
      nostalgia maintains psychological comfort. Here, we propose, and document in five
      methodologically diverse studies, a broader homeostatic function for nostalgia
      that also encompasses the maintenance of physiological comfort. We show that
      nostalgia--an emotion with a strong connotation of warmth--is triggered by
      coldness. Participants reported stronger nostalgia on colder (vs. warmer) days
      and in a cold (vs. neutral or warm) room. Nostalgia, in turn, modulates the
      interoceptive feeling of temperature. Higher levels of music-evoked nostalgia
      predicted increased physical warmth, and participants who recalled a nostalgic
      (vs. ordinary autobiographical) event perceived ambient temperature as higher.
      Finally, and consistent with the close central nervous system integration of
      temperature and pain sensations, participants who recalled a nostalgic (vs.
      ordinary autobiographical) event evinced greater tolerance to noxious cold.

PMID- 22390712
TI  - Competition effects of threatening faces in social anxiety.
AB  - Threatening faces involuntarily grab attention in socially anxious individuals.
      It is unclear, however, whether attention capture is at the expense of concurrent
      visual processing. The current study examined the perceptual cost effects of
      viewing fear-relevant stimuli (threatening faces) relative to a concurrent change
      detection task. Steady-state visual evoked potentials (ssVEPs) were used to
      separate the neural response to 2 fully overlapping types of stimuli flickering
      at different frequencies: Task-irrelevant facial expressions (angry, neutral,
      happy) were overlaid with a task-relevant Gabor patch stream, which required a
      response to rare phase reversals. Groups of 17 high and 17 low socially anxious
      observers were recruited through online prescreening of 849 students. A prominent
      competition effect of threatening faces was observed solely in elevated social
      anxiety: When an angry face, relative to a neutral or happy face, served as a
      distractor, heightened ssVEP amplitudes were seen at the tagging frequency of
      that facial expression. Simultaneously, the ssVEP evoked by the task-relevant
      Gabor grating was reliably diminished compared with conditions with neutral or
      happy distractor faces. Thus, threatening faces capture and hold low-level
      perceptual resources in viewers symptomatic for social anxiety at the cost of a
      concurrent primary task. It is important to note that this competition in lower
      tier visual cortex was maintained throughout the viewing period and was
      unaccompanied by competition effects on behavioral performance.

PMID- 22390714
TI  - A VUV photoionization study of the combustion-relevant reaction of the phenyl
      radical (C6H5) with propylene (C3H6) in a high temperature chemical reactor.
AB  - We studied the reaction of phenyl radicals (C(6)H(5)) with propylene (C(3)H(6))
      exploiting a high temperature chemical reactor under combustion-like conditions
      (300 Torr, 1200-1500 K). The reaction products were probed in a supersonic beam
      by utilizing tunable vacuum ultraviolet (VUV) radiation from the Advanced Light
      Source and recording the photoionization efficiency (PIE) curves at mass-to
      charge ratios of m/z = 118 (C(9)H(10)(+)) and m/z = 104 (C(8)H(8)(+)). Our
      results suggest that the methyl and atomic hydrogen losses are the two major
      reaction pathways with branching ratios of 86 +/- 10% and 14 +/- 10%. The isomer
      distributions were probed by fitting the recorded PIE curves with a linear
      combination of the PIE curves of the individual C(9)H(10) and C(8)H(8) isomers.
      Styrene (C(6)H(5)C(2)H(3)) was found to be the exclusive product contributing to
      m/z = 104 (C(8)H(8)(+)), whereas 3-phenylpropene, cis-1-phenylpropene, and 2
      phenylpropene with branching ratios of 96 +/- 4%, 3 +/- 3%, and 1 +/- 1% could
      account for the signal at m/z = 118 (C(9)H(10)(+)). Although searched for
      carefully, no evidence of the bicyclic indane molecule could be provided. The
      reaction mechanisms and branching ratios are explained in terms of electronic
      structure calculations nicely agreeing with a recent crossed molecular beam study
      on this system.

PMID- 22390715
TI  - Yeast hypertrophy: cause or consequence of aging? Reply to Bilinski et al.

PMID- 22390716
TI  - Accuracy and reliability of cone beam computed tomography of the jaws for
      comparative forensic identification: a preliminary study.
AB  - Conventional computed tomography is an emerging modality in forensic
      identification but is not sufficiently accurate for use in dental identification
      primarily because of problems with metallic dental restoration-induced streak
      artifact. In this study, the accuracy and reliability of recording forensic
      information from cone beam computed tomography (CBCT) scans of the jaws when
      compared to conventional panoramic radiographs has been analyzed under
      experimental conditions. Information could be recorded with near-perfect
      repeatability and reproducibility. Information could also be recorded accurately,
      the sensitivity being 96.6% (95% CI, 95.1-98.1) and specificity being 98.4% (95%
      CI, 96.2-100). The metal dental restoration-induced streak artifact was at a
      level that permitted, in most cases, accurate observations. This is considered an
      important step in validating CBCT as a tool in comparative dental identification
      of bodies. It may have a role in mass fatalities and in chemical, biological,
      radiological, and nuclear incidents, but further studies are required to assess
      the feasibility of this.

PMID- 22390718
TI  - Application of PCA and SIMCA statistical analysis of FT-IR spectra for the
      classification and identification of different slag types with environmental
      origin.
AB  - In the past, different slag materials were often used for landscaping and
      construction purposes or simply dumped. Nowadays German environmental laws
      strictly control the use of slags, but there is still a remaining part of 35%
      which is uncontrolled dumped in landfills. Since some slags have high heavy metal
      contents and different slag types have typical chemical and physical properties
      that will influence the risk potential and other characteristics of the deposits,
      an identification of the slag types is needed. We developed a FT-IR-based
      statistical method to identify different slags classes. Slags samples were
      collected at different sites throughout various cities within the industrial Ruhr
      area. Then, spectra of 35 samples from four different slags classes, ladle
      furnace (LF), blast furnace (BF), oxygen furnace steel (OF), and zinc furnace
      slags (ZF), were determined in the mid-infrared region (4000-400 cm(-1)). The
      spectra data sets were subject to statistical classification methods for the
      separation of separate spectral data of different slag classes. Principal
      component analysis (PCA) models for each slag class were developed and further
      used for soft independent modeling of class analogy (SIMCA). Precise
      classification of slag samples into four different slag classes were achieved
      using two different SIMCA models stepwise. At first, SIMCA 1 was used for
      classification of ZF as well as OF slags over the total spectral range. If no
      correct classification was found, then the spectrum was analyzed with SIMCA 2 at
      reduced wavenumbers for the classification of LF as well as BF spectra. As a
      result, we provide a time- and cost-efficient method based on FT-IR spectroscopy
      for processing and identifying large numbers of environmental slag samples.

PMID- 22390717
TI  - Characterisation of the vitreous proteome in proliferative diabetic retinopathy.
AB  - BACKGROUND: Diabetes can lead to serious microvascular complications such as
      proliferative diabetic retinopathy (PDR), which results in severe vision loss.
      The diabetes-induced alterations in the vitreous protein composition in diabetic
      patients with PDR may be responsible for the presence of PDR. The vitreous humour
      can be utilised in a variety of studies aimed toward the discovery of new targets
      for the treatment or prevention of PDR and the identification of novel disease
      mechanisms. The aim of this study was to compare the protein profile of vitreous
      humour from diabetic patients with PDR with that of vitreous humour from normal
      human eyes donated for corneal transplant. RESULTS: Vitreous humour from type 2
      diabetic patients with PDR (n = 10) and from normal human eyes donated for
      corneal transplant (n = 10) were studied. The comparative proteomic analysis was
      performed using two-dimensional fluorescence difference gel electrophoresis (2-D
      DIGE). Differentially produced proteins (abundance ratio > 2 or < -2, p < 0.01)
      were identified by matrix-assisted laser desorption ionisation time-of-flight
      mass spectrometry (MALDI-TOF MS) and MALDI-TOF tandem mass spectrometry. A total
      of 1242 protein spots were detected on the 2-D master gel of the samples, and 57
      spots that exhibited statistically significant variations were successfully
      identified. The spots corresponded to peptide fragments of 29 proteins, including
      8 proteins that increased and 21 proteins that decreased in PDR. Excluding the
      serum proteins from minor vitreous haemorrhage, 19 proteins were found to be
      differentially produced in PDR patients compared with normal subjects; 6 of these
      proteins have never been reported to be differentially expressed in PDR vitreous:
      N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH 1), tubulin alpha-1B
      chain, gamma-enolase, cytosolic acyl coenzyme A thioester hydrolase, malate
      dehydrogenase and phosphatidylethanolamine-binding protein 1 (PEBP 1). The
      differential production of pigment epithelium-derived factor (PEDF) and clusterin
      was confirmed by Western blot analysis. CONCLUSIONS: These data provide an in
      depth analysis of the human vitreous proteome and reveal protein alterations that
      are possibly involved in the pathogenesis of PDR. Further investigation of these
      special proteins may provide potential new targets for the treatment or the
      prevention of PDR.

PMID- 22390720
TI  - Value of immediate second resection of the tumor bed to improve the effectiveness
      of transurethral resection of bladder tumor.
AB  - BACKGROUND AND PURPOSE: Current guidelines recommend routine second transurethral
      resection (TUR) for accurate diagnosis and to prevent understaging of muscle
      invasive bladder cancer. We evaluated the diagnostic accuracy of immediate second
      resection of the tumor bed during initial TUR and its prognostic significance.
      PATIENTS AND METHODS: Patients (n=126) undergoing TUR were prospectively
      randomized to undergo (n=63) or not undergo (n=63) immediate second resection of
      the tumor bed after complete TUR. Second resection was repeated until muscularis
      propria (MP) was identified in the specimen and the depth of tumor invasion was
      inspected. The results of second resection were compared with final pathology
      results for diagnostic accuracy. Recurrence and progression rates were compared
      in the two groups, and factors affecting recurrence were evaluated. RESULTS:
      Patient age, sex distribution, number of tumors, pathologic T stage and grade
      were similar in the groups. MP was included in all TUR specimens in the immediate
      second resection group, compared with 41 of 63 (65.1%) in the nonsecond resection
      group. The concordance rate of second resection with final pathology was r=0.810
      (P<0.01). The sensitivity and specificity of second resection for T(2) disease
      were 90.9% and 98.0%, respectively, and the positive and negative predictive
      values of second resection for T(2) disease were 90.0% and 96.2%, respectively.
      Among the 94 patients followed up, those in the second resection group had
      significantly higher 2-year recurrence-free survival rate (77.0% vs 45.8%,
      P=0.025), but there was no difference in progression-free survival rate.
      CONCLUSIONS: Immediate second resection of the tumor bed after complete TUR
      improves the effectiveness of resection by immediately confirming the presence of
      MP in the specimen and accurately differentiating muscle-invasive disease. The
      advantages of immediate second resection were precise prediction of final
      pathology results and reduced early recurrence.

PMID- 22390722
TI  - Commentary on "Comparison of cosmetic outcome between single-incision
      laparoscopic cholecystectomy and conventional laparoscopic cholecystectomy: an
      objective study".

PMID- 22390719
TI  - Outcome of acute myeloid leukaemia following myelodysplastic syndrome after
      azacitidine treatment failure.

PMID- 22390723
TI  - Antimicrobial susceptibility testing in 90 min by bacterial cell count
      monitoring.
AB  - The rise in antimicrobial resistance has become a serious global health problem.
      Restrictive use of antibiotics seems the only option to temper this accession
      since research in new antibiotics has halted. Antimicrobial stewardship
      programmes rely on quick access to susceptibility data. This study evaluated the
      concept of bacterial cell count monitoring as a fast method to determine
      susceptibility. Escherichia coli, Pseudomonas aeruginosa and Staphylococcus
      aureus strains were tested for amoxicillin/piperacillin and gentamicin by three
      conventional methods (VITEK2((r)) , Etest((r)) and broth-macrodilution).
      Bacterial cell count monitoring reliably predicted susceptibility after 90 min
      for Escherichia coli and after 120 min for Pseudomonas aeruginosa and
      Staphylococcus aureus without any minor, major or very major discrepancies. Time
      to-result was reduced by 74%, 83% and 76%, respectively. Bacterial cell count
      monitoring shows great potential for rapid susceptibility testing.

PMID- 22390724
TI  - Genetic and physical interaction of Meis2, Pax3 and Pax7 during dorsal midbrain
      development.
AB  - BACKGROUND: During early stages of brain development, secreted molecules,
      components of intracellular signaling pathways and transcriptional regulators act
      in positive and negative feed-back or feed-forward loops at the mid-hindbrain
      boundary. These genetic interactions are of central importance for the
      specification and subsequent development of the adjacent mid- and hindbrain. Much
      less, however, is known about the regulatory relationship and functional
      interaction of molecules that are expressed in the tectal anlage after tectal
      fate specification has taken place and tectal development has commenced. RESULTS:
      Here, we provide experimental evidence for reciprocal regulation and subsequent
      cooperation of the paired-type transcription factors Pax3, Pax7 and the TALE
      homeodomain protein Meis2 in the tectal anlage. Using in ovo electroporation of
      the mesencephalic vesicle of chick embryos we show that (i) Pax3 and Pax7
      mutually regulate each other's expression in the mesencephalic vesicle, (ii)
      Meis2 acts downstream of Pax3/7 and requires balanced expression levels of both
      proteins, and (iii) Meis2 physically interacts with Pax3 and Pax7. These results
      extend our previous observation that Meis2 cooperates with Otx2 in tectal
      development to include Pax3 and Pax7 as Meis2 interacting proteins in the tectal
      anlage. CONCLUSION: The results described here suggest a model in which
      interdependent regulatory loops involving Pax3 and Pax7 in the dorsal
      mesencephalic vesicle modulate Meis2 expression. Physical interaction with Meis2
      may then confer tectal specificity to a wide range of otherwise broadly expressed
      transcriptional regulators, including Otx2, Pax3 and Pax7.

PMID- 22390725
TI  - Relative performance of different dental professional groups in screening for
      occlusal caries.
AB  - OBJECTIVES: The use of role substitution, where different levels of practitioner
      undertake the duties of the most qualified clinician, is common in medicine and
      dentistry. Proponents argue that role substitution has the potential to increase
      dentists' efficiency and effectiveness, thereby freeing up resources to improve
      access and reduce oral health inequalities. Given the current global economic
      climate, many countries are re-examining models of service provision to utilize
      role substitution. The objective of this study was to determine whether different
      members of the dental team could meet the diagnostic threshold set by the World
      Health Organization, when screening photographs of occlusal surfaces for dental
      caries. METHODS: Participants were sampled purposively and included; final-year
      dental students, final-year hygiene-therapy students, primary care dentists,
      hygiene-therapists and dental nurses. Following a brief training package,
      participants were asked to score 102 clinical photographs of both carious and
      noncarious extracted teeth and determine whether the tooth was 'healthy' or had
      'suspected decay'. The time delay between consecutive photographs was set at 8-s.
      Judgment decisions were compared against the International Caries Detection and
      Assessment System as the gold standard, with scores of two or less representing
      'healthy'. Sensitivity, specificity and predictive values were determined for
      each participant and clinical group. Kappa was calculated to determine test
      retest reliability. RESULTS: Dental nurses had the highest median sensitivity
      (87.9%), although all groups were comparable. The median specificity for the
      groups was lower than their sensitivity scores, with dentists scoring the highest
      (71.0%). Dentists also scored the highest median positive predictive value
      (57.8%), whilst dental nurses scored the highest negative predictive value
      (91.3%). The median level of agreement was high for all groups; the highest
      median score was for the final-year dental students (88.9%). CONCLUSIONS: Even
      with minimal training, different members of the dental team show the potential to
      screen for occlusal caries to a similar standard as primary care dentists. This
      requires further testing in vivo, but has important implications for the
      productivity and design of the future dental workforce.

PMID- 22390727
TI  - Gold nanoparticles assembling on smooth silver spheres for surface-enhanced Raman
      spectroscopy.
AB  - A simple and cost-effective chemical method was introduced to assemble gold (Au)
      nanoparticles on smooth silver (Ag) spheres for realizing surface-enhanced Raman
      scattering (SERS) enhancement by the replacement reaction between chloroauric
      acid and Ag spheres. In addition, the Ag-Au core-shell spheres were fabricated
      when a certain amount of chloroauric acid was used in the reaction solution. We
      found that the Ag particles decorated with small Au nanoparticles demonstrated
      the strongest SERS enhancement, while Ag-Au core-shell spheres showed the weakest
      enhancement.

PMID- 22390726
TI  - Cnidocyte discharge is regulated by light and opsin-mediated phototransduction.
AB  - BACKGROUND: Cnidocytes, the eponymous cell type of the Cnidaria, facilitate both
      sensory and secretory functions and are among the most complex animal cell types
      known. In addition to their structural complexity, cnidocytes display complex
      sensory attributes, integrating both chemical and mechanical cues from the
      environment into their discharge behavior. Despite more than a century of work
      aimed at understanding the sensory biology of cnidocytes, the specific sensory
      receptor genes that regulate their function remain unknown. RESULTS: Here we
      report that light also regulates cnidocyte function. We show that non-cnidocyte
      neurons located in battery complexes of the freshwater polyp Hydra magnipapillata
      specifically express opsin, cyclic nucleotide gated (CNG) ion channel and
      arrestin, which are all known components of bilaterian phototransduction
      cascades. We infer from behavioral trials that different light intensities elicit
      significant effects on cnidocyte discharge propensity. Harpoon-like stenotele
      cnidocytes show a pronounced diminution of discharge behavior under bright light
      conditions as compared to dim light. Further, we show that suppression of firing
      by bright light is ablated by cis-diltiazem, a specific inhibitor of CNG ion
      channels. CONCLUSIONS: Our results implicate an ancient opsin-mediated
      phototransduction pathway and a previously unknown layer of sensory complexity in
      the control of cnidocyte discharge. These findings also suggest a molecular
      mechanism for the regulation of other cnidarian behaviors that involve both
      photosensitivity and cnidocyte function, including diurnal feeding repertoires
      and/or substrate-based locomotion. More broadly, our findings highlight one
      novel, non-visual function for opsin-mediated phototransduction in a cnidarian,
      the origins of which might have preceded the evolution of cnidarian eyes.

PMID- 22390728
TI  - Can interprofessional collaboration provide health human resources solutions? A
      knowledge synthesis.
AB  - Many studies examine the impact of interprofessional (IP) interventions on
      various health practice and education outcomes. One significant gap is the lack
      of research on the effects of IP interventions on health human resource (HHR)
      outcomes. This project synthesized the literature on the impact of IP
      interventions at the pre- and post-licensure levels on quality workplace, staff
      satisfaction, recruitment, retention, turnover, choice of employment and cost
      effectiveness. Forty-one peer-reviewed articles and five IECPCP project reports
      were included in the review. We found that IP interventions at the post-licensure
      level improved provider satisfaction and workplace quality. Including IP learning
      opportunities into practice education in rural communities or in less popular
      healthcare specialties attracted a higher number of students and therefore may
      increase employment rates. This area requires more high quality studies to firmly
      establish the effectiveness of IP interventions in recruiting and retaining
      future healthcare professionals. There is strong evidence that IP interventions
      at the post-licensure level reduced patient care costs. The knowledge synthesis
      has enhanced our understanding of the relationships between IP interventions, IP
      collaboration and HHR outcomes. Gaps remain in the knowledge of staff retention
      and determination of staffing costs associated with IP interventions vis-a-vis
      patient care costs. None of the studies reported long-term data on graduate
      employment choice, which is essential to fully establish the effectiveness of IP
      interventions as a HHR recruitment strategy.

PMID- 22390729
TI  - Understanding health behaviours in a cohort of pregnant women at risk of
      gestational diabetes mellitus: an observational study.
AB  - OBJECTIVE: To assess health behaviours, physical activity levels, weight gain and
      development of gestational diabetes mellitus (GDM) in high-risk women. DESIGN: An
      observational sub-study of a larger randomised controlled trial. SETTING: A large
      tertiary hospital in Australia. POPULATION: Ninety-seven women (mean age 31.7 +/-
      4.5 years; body mass index 30.3 +/- 5.9 kg/m(2) ) at risk of developing GDM.
      METHODS: Women were identified as at risk of GDM based on a validated screening
      tool. Baseline measures were completed at 12-15 weeks of gestation and repeated
      at 26-28 weeks of gestation. MAIN OUTCOME MEASURES: Anthropometric (weight and
      height) and physical activity assessment (Yamax pedometer and International
      physical activity questionnaire), questionnaires (self-efficacy) and GDM
      screening. RESULTS: By 28 weeks of gestation, there was a high GDM prevalence of
      26% using the recent International Association of Diabetes and Pregnancy Study
      Group criteria. Weight gain in overweight (body mass index 25-29.9 kg/m(2)) and
      obese (body mass index >30.0 kg/m(2)) women exceeded minimum total weight gain
      recommendations set by the Institute of Medicine (P < 0.01). Physical activity
      levels were low and declined during pregnancy (5437 +/- 2951 steps/day to 4096 +/
      2438 steps/day, respectively, P < 0.001). Despite reduced activity levels,
      increased weight gain and high GDM incidence many women did not accurately
      perceive GDM risk and were confident in their ability to control weight. A
      significant association with physical activity, weight and GDM outcome was not
      observed. CONCLUSIONS: Overweight and obese pregnant women at risk for developing
      GDM demonstrate excessive weight gain and a reduced level of physical activity
      observed from early pregnancy to 28 weeks of gestation. Results highlight the
      need for targeted intervention in women at risk for developing GDM.

PMID- 22390730
TI  - Solution structure of the Dickerson DNA dodecamer containing a single
      ribonucleotide.
AB  - Ribonucleotides are frequently incorporated into DNA during replication. They are
      recognized and processed by several cellular enzymes, and their continued
      presence in the yeast nuclear genome results in replicative stress and genome
      instability. Thus, it is important to understand the effects of isolated
      ribonucleotide incorporation on DNA structure. With this goal in mind, we
      describe the nuclear magnetic resonance structure of the self-complementary
      Dickerson dodecamer sequence [d(CGC)rGd(AATTCGCG)](2) containing two
      symmetrically positioned riboguanosines. The absence of an observable H(1)-H(2)
      scalar coupling interaction indicates a C3'-endo conformation for the ribose.
      Longer-range structural perturbations resulting from the presence of the
      ribonucleotide are limited to the adjacent and transhelical nucleotides, while
      the global B-form DNA structure is maintained. Because crystallographic studies
      have indicated that isolated ribonucleotides promote global B -> A transitions,
      we also performed molecular modeling analyses to evaluate the structural
      consequences of higher ribonucleotide substitution levels. Increasing the
      ribonucleotide content increased the minor groove width toward values more
      similar to that of A-DNA, but even 50% ribonucleotide substitution did not fully
      convert the B-DNA to A-DNA. Comparing our structure with the structure of an
      RNase H2-bound DNA supports the conclusion that, as with other DNA-protein
      complexes, the DNA conformation is strongly influenced by the interaction with
      the protein.

PMID- 22390732
TI  - Consumer involvement in systematic reviews of comparative effectiveness research.
AB  - BACKGROUND: The Institute of Medicine recently recommended that comparative
      effectiveness research (CER) should involve input from consumers. While
      systematic reviews are a major component of CER, little is known about consumer
      involvement. OBJECTIVE: To explore current approaches to involving consumers in
      US-based and key international organizations and groups conducting or
      commissioning systematic reviews ('organizations'). DESIGN: In-depth, semi
      structured interviews with key informants and review of organizations' websites.
      SETTING AND PARTICIPANTS: Seventeen highly regarded US-based and international
      (Cochrane Collaboration, Campbell Collaboration) organizations. RESULTS:
      Organizations that usually involve consumers (seven of 17 in our sample) involve
      them at a programmatic level in the organization or in individual reviews through
      one-time consultation or on-going collaboration. For example, consumers may
      suggest topics, provide input on the key questions of the review, provide
      comments on draft protocols and reports, serve as co-authors or on an advisory
      group. Organizations involve different types of consumers (individual patients,
      consumer advocates, families and caregivers), recruiting them mainly through
      patient organizations and consumer networks. Some offer training in research
      methods, and one developed training for researchers on how to involve consumers.
      Little formal evaluation of the effects of consumer involvement is being carried
      out. CONCLUSIONS: Consumers are currently involved in systematic reviews in a
      variety of ways and for various reasons. Assessing which approaches are most
      effective in achieving different aims of consumer involvement is now required to
      inform future recommendations on consumer involvement in CER.

PMID- 22390731
TI  - Escherichia coli low-molecular-weight penicillin-binding proteins help orient
      septal FtsZ, and their absence leads to asymmetric cell division and branching.
AB  - Escherichia coli cells lacking low-molecular-weight penicillin-binding proteins
      (LMW PBPs) exhibit morphological alterations that also appear when the septal
      protein FtsZ is mislocalized, suggesting that peptidoglycan modification and
      division may work together to produce cell shape. We found that in strains
      lacking PBP5 and other LMW PBPs, higher FtsZ concentrations increased the
      frequency of branched cells and incorrectly oriented Z rings by 10- to 15-fold.
      Invagination of these rings produced improperly oriented septa, which in turn
      gave rise to asymmetric cell poles that eventually elongated into branches.
      Branches always originated from the remnants of abnormal septation events,
      cementing the relationship between aberrant cell division and branch formation.
      In the absence of PBP5, PBP6 and DacD localized to nascent septa, suggesting that
      these PBPs can partially substitute for the loss of PBP5. We propose that
      branching begins when mislocalized FtsZ triggers the insertion of inert
      peptidoglycan at unusual positions during cell division. Only later, after normal
      cell wall elongation separates the patches, do branches become visible. Thus, a
      relationship between the LMW PBPs and cytoplasmic FtsZ ultimately affects cell
      division and overall shape.

PMID- 22390733
TI  - Absolute configuration and total synthesis of a novel antimalarial lipopeptide by
      the de novo preparation of chiral nonproteinogenic amino acids.
AB  - The absolute configuration (via degradation and Marfey's derivatization studies)
      and the total synthesis of a novel antimalarial lipid-peptide isolated from
      Streptomyces sp. (IC(50) = 0.8 MUM, Plasmodium falciparum 3D7) is disclosed. To
      this end, versatile stereocontrolled routes to nonproteinogenic amino acids (via
      catalytic Mannich, Sharpless methods) and enantiomeric trans fatty acids (via
      Evans alkylation, Kocienski-Julia olefination) have been developed.

PMID- 22390734
TI  - Dutch translation and cross-cultural adaptation of the PROMIS(r) physical
      function item bank and cognitive pre-test in Dutch arthritis patients.
AB  - INTRODUCTION: Patient-reported physical function is an established outcome domain
      in clinical studies in rheumatology. To overcome the limitations of the current
      generation of questionnaires, the Patient-Reported Outcomes Measurement
      Information System (PROMIS(r)) project in the USA has developed calibrated item
      banks for measuring several domains of health status in people with a wide range
      of chronic diseases. The aim of this study was to translate and cross-culturally
      adapt the PROMIS physical function item bank to the Dutch language and to pretest
      it in a sample of patients with arthritis. METHODS: The items of the PROMIS
      physical function item bank were translated using rigorous forward-backward
      protocols and the translated version was subsequently cognitively pretested in a
      sample of Dutch patients with rheumatoid arthritis. RESULTS: Few issues were
      encountered in the forward-backward translation. Only 5 of the 124 items to be
      translated had to be rewritten because of culturally inappropriate content.
      Subsequent pretesting showed that overall, questions of the Dutch version were
      understood as they were intended, while only one item required rewriting.
      CONCLUSIONS: Results suggest that the translated version of the PROMIS physical
      function item bank is semantically and conceptually equivalent to the original.
      Future work will be directed at creating a Dutch-Flemish final version of the
      item bank to be used in research with Dutch speaking populations.

PMID- 22390735
TI  - A phase II study of risk-adapted intravenous melphalan in patients with AL
      amyloidosis.

PMID- 22390736
TI  - Cross-generational effects of discrimination among immigrant mothers: perceived
      discrimination predicts child's healthcare visits for illness.
AB  - OBJECTIVE: This study tested whether an immigrant mother's perception of ethnic
      and language-based discrimination affects the health of her child (indexed by the
      child's frequency of sick visits to the doctor, adjusting for well-visits), as a
      function of her ethnic-group attachment and length of U.S. residency. METHOD: A
      community-based sample of 98 immigrant Dominican and Mexican mothers of normally
      developing 14-month-old children were interviewed. Mothers reported their
      perceived ethnic and language-based discrimination, degree of ethnic-group
      attachment, length of time in the United States, and frequency of their child's
      doctor visits for both illness and routine (healthy) exams. RESULTS: Among more
      recent immigrants, greater perceived ethnic and language-based discrimination
      were associated with more frequent sick-child visits, but only among those
      reporting low ethnic-group attachment. The associations between both forms of
      perceived discrimination and sick-child visits were not observed among mothers
      reporting high ethnic-group attachment. Among more established immigrants,
      perceived language-based discrimination was associated with more frequent sick
      child visits regardless of ethnic-group attachment. CONCLUSION: These results
      suggest that a Latina mother's experience with ethnic and language-based
      discrimination is associated with her child's health, as indicated by doctor
      visits for illness, but that strong ethnic-group attachment may mitigate this
      association among recent immigrants.

PMID- 22390737
TI  - Illness perception ratings of high-risk newborns by mothers and clinicians:
      relationship to illness severity and maternal stress.
AB  - OBJECTIVE: Patients' views of illness are often thought to differ from those of
      medical staff, although this is rarely assessed. This study examined the
      correspondence between mothers' and clinicians' perceptions of the same high-risk
      newborns, as well as with an objective measure of illness severity. We also
      investigated how mothers' perceptions were related to reported stress. METHODS:
      Mothers of 99 high-risk infants admitted to either a neonatal intensive care or
      neonatal high dependency unit, which offers specialized but not intensive care,
      completed illness perception ratings of their baby's condition as well as
      perceived stress 3 to 5 days following admission. At the same time, a
      standardized measure of neonatal illness severity was calculated and the baby's
      primary neonatologist completed illness perceptions ratings. RESULTS: Unlike
      clinician ratings, mothers' illness perceptions were not significantly correlated
      with illness severity. Mothers generally rated babies in both units as sicker and
      having a more serious illness than did neonatologists. Whereas clinicians,
      compared with mothers, rated babies in intensive care as having an illness that
      would affect their life more and last for a longer time. Mothers rated medical
      treatment to be significantly more helpful than did clinicians, particularly for
      babies admitted to the high dependency unit. Mothers' stress was significantly
      associated with illness perceptions but unrelated to illness severity.
      CONCLUSIONS: Significant differences exist in the perceptions of illness
      severity, helpfulness of treatment, and the long-term effects of the baby's
      illness between parents and clinicians and this may lead to misunderstandings and
      misinterpretations in communication.

PMID- 22390738
TI  - Self-regulatory processes mediate the intention-behavior relation for adherence
      and exercise behaviors.
AB  - OBJECTIVES: Understanding the gap between people's intentions and actual health
      behavior is an important issue in health psychology. Our aim in this study was to
      investigate whether self-regulatory processes (monitoring goal progress and
      responding to discrepancies) mediate the intention-behavior relation in relation
      to HIV medication adherence (Study 1) and intensive exercise behavior (Study 2).
      METHOD: In Study 1, questionnaire and electronically monitored adherence data
      were collected at baseline and 3 months later from patients in the control arm of
      an HIV-adherence intervention study. In Study 2, questionnaire data was collected
      at 3 time points 6-weeks apart in a cohort study of physical activity. RESULTS:
      Complete data at all time points were obtained from 51 HIV-infected patients and
      499 intensive exercise participants. Intentions were good predictors of behavior
      and explained 25 to 30% of the variance. Self-regulatory processes explained an
      additional 11% (Study 1) and 6% (Study 2) of variance in behavior on top of
      intentions. Regression and bootstrap analyses revealed at least partial, and
      possibly full, mediation of the intention-behavior relation by self-regulatory
      processes. CONCLUSIONS: The present studies indicate that self-regulatory
      processes may explain how intentions drive behavior. Future tests, using
      different health behaviors and experimental designs, could firmly establish
      whether self-regulatory processes complement current health behavior theories and
      should become routine targets for intervention. (PsycINFO Database Record (c)
      2012 APA, all rights reserved).

PMID- 22390739
TI  - Experimental evidence for the intention-behavior relationship in the physical
      activity domain: a meta-analysis.
AB  - OBJECTIVE: Most contemporary theories of physical activity include an intention
      construct as the proximal determinant of behavior. Support of this premise has
      been found through correlational research. The purpose of this paper was to
      appraise the experimental evidence for the intention-behavior relationship
      through meta-analysis. METHODS: Studies were eligible if they included: (1)
      random assignment of participants to intervention/no intervention groups; (2) an
      intervention that produced a significant difference in intention between groups;
      and (3) a measure of behavior was taken after the intention measure. Literature
      searches were concluded in December 2010 among five key search engines. RESULTS:
      This search yielded a total of 1,033 potentially relevant records; of these, 11
      passed the eligibility criteria. Random effects meta-analysis procedures with
      correction for sampling bias were employed in the analysis. The sample-weighted
      average effect size derived from these studies was d+ = .45 (95% CI .30 to .60)
      for intention, yet d+ = .15 (95% CI .06 to .23) for behavior. CONCLUSIONS: These
      results demonstrate a weak relationship between intention and behavior that may
      be below meaningful/practical value. We suggest that prior evidence was probably
      biased by the limits of correlation coefficients in passive designs. It is
      recommended that contemporary research apply models featuring intention-behavior
      mediators or action control variables in order to account for this intention
      behavior gap.

PMID- 22390740
TI  - Pathological impairments induced by interstitial implantation of 125I seeds in
      spinal canal of banna mini-pigs.
AB  - BACKGROUND: Use a banna mini-pig to set up 125I implantation model, and
      investigate the consequence of radiation-related impairments. METHODS: In present
      study, 125I seeds were implanted into spinal canal of T13 level of spine in banna
      mini-pigs. After operation, the pigs were raised up to 8 months, behavior changes
      were recorded within this period. After 8 months, spinal cords were collected for
      pathological analysis. RESULTS: In this study, a 125I brachytherapy animal model
      had been successfully established, in the model group, the banna pigs' Tarlov
      scale decreased from 5 to 2.57 +/- 0.36, significant cellular impairments were
      noted by pathological analysis. CONCLUSIONS: Without any protection and operation
      improvement, 125I implantation can cause serious histological impairments and
      moving difficulty for banna mini-pigs; this present research provides an
      alternative tool to study spinal 125I brachytherapy.

PMID- 22390741
TI  - Age-related trends of Stroop-like interference in animal size tests in 5- to 12
      year-old children and young adults.
AB  - Few studies have examined the development of Prepotent Response Inhibition
      (Nigg's interference control) from childhood to adulthood. This cross-sectional
      study examined differences in Prepotent Response Inhibition among children of 5
      age groups: twenty 5- to 6-year-olds, twenty-one 7- to 8-year-olds, twenty-two 9-
      to 10-year-olds, eighteen 11- to 12-year-olds, and 24 young adults (18- to 24
      year-olds). Participants were administered two Stroop-like tasks: the Real Animal
      Size Test described in 2009 by Catale and Meulemans, which requires that
      participants decide the real size of animals (big vs. small) displayed in a
      mismatching pictorial size; and the Pictorial Animal Size Test (an original
      test), which requires that participants report the pictorial size of the animals.
      Results showed clear differences between the tests. The Pictorial Animal Size
      Test elicited robust interference whereas the Real Animal Size Test elicited no
      interference. The Pictorial Animal Size Test also revealed the development of
      Prepotent Response Inhibition in children of 5-12 years and between children and
      young adults. These results were discussed with respect to differences in
      strengths of processing. The Pictorial Animal Size Test can be a useful tool for
      assessment of Prepotent Response Inhibition in children older than 5 years of
      age.

PMID- 22390742
TI  - The use of mineral trioxide aggregate to achieve root end closure: three case
      reports.
AB  - The use of mineral trioxide aggregate (MTA) to achieve root end closure has many
      advantages over the traditional calcium hydroxide (Ca(OH)2) technique including
      the reduced number of visits and the reduced mechanical damage to dentine.
      Limited studies have reported the outcome of using MTA as an apexification
      material and a one-stage obturation technique in non-vital immature teeth. This
      article illustrates three successful clinical cases where MTA was used as an
      apexification material. In case study one: Type 1 Dens Invaginatus tooth with
      incomplete root formation, case study two: an immature tooth that suffered pulp
      necrosis following an enamel and dentine fracture trauma and case study three: a
      non-vital tooth following an apical root fracture.

PMID- 22390743
TI  - Morphological and syntactic skills in language samples of pre school aged
      children with autism: atypical development?
AB  - This study investigated whether children with autism have atypical development of
      morphological and syntactic skills, including whether they use rote learning to
      compensate for impaired morphological processing and acquire grammatical
      morphemes in an atypical order. Participants were children aged from 3-6 years
      who had autism (n = 17), developmental delay without autism (n = 7), and
      typically-developing children (n = 19). Language samples were taken from
      participants during the administration of the Autism Diagnostic Observation
      Schedule, and transcripts were coded using the Index of Productive Syntax, and
      for usage of Brown's grammatical morphemes. Participants were also administered
      an elicitation task requiring the application of inflections to non-words; the
      Wugs Task. The main finding of this study was that children with autism have
      unevenly developed morphological and syntactic sub-skills; they have skills which
      are a combination of intact, delayed, and atypical. It was also found that
      children with autism and children with developmental delays can acquire and use
      morphological rules. The implications of these findings are that, in order to
      maximize language acquisition for these children, clinicians need to utilize
      comprehensive language assessment tools and design interventions that are
      tailored to the child's strengths and weaknesses.

PMID- 22390744
TI  - Parents' expectations, awareness, and experiences of accessing evidence-based
      speech-language pathology services for their children with autism.
AB  - The aim of this study was to explore the expectations, awareness, and experiences
      of parents in their efforts to access evidence-based speech-language pathology
      (SLP) services for their children with autism spectrum disorders (ASD). Four
      focus groups were conducted with 20 parents of pre school aged children with ASD
      and transcripts were analysed using thematic analysis. Two themes emerged to
      account for the participants' expectations, awareness, and experiences. The two
      themes, "Speech-language pathology: More than just a business", and "Parents and
      power", represented the complex interaction between factors including the
      parents' access to information, their involvement in the therapy process, and
      their sense of empowerment. The parents in this study expressed a strong desire
      for evidence-based practice (EBP) to be employed. However, the parents had
      different views on how EBP should be achieved. The findings of this study
      demonstrate the importance of involving parents in therapeutic relationships as
      partners in the decision-making process. This means providing parents with
      comprehensive information, including research evidence to support the clinical
      decisions that need to be made, and respecting parents' preferences in the
      therapy process.

PMID- 22390745
TI  - Clinical investigation of the Global Voice Therapy Model.
AB  - The purpose of this study was to investigate the effect of the Global Voice
      Therapy Model (GVTM) on acoustic, aerodynamic, and perceptual voice measures of
      four adults seeking voice therapy for a voice disorder. A speech-language
      pathologist facilitated speaking voice therapy with the four participants using
      the GVTM. Participants completed acoustic, aerodynamic, and perceptual voice
      measures at pre- and post-therapy time points. Differences were seen in the voice
      measures from pre- to post-therapy. The GVTM was successful in facilitating an
      improvement in the acoustic, aerodynamic, and perceptual measures of the
      participants.

PMID- 22390746
TI  - Use of simulated patients for a student learning experience on managing difficult
      patient behaviour in speech-language pathology contexts.
AB  - A student learning experience about managing difficult patients in speech
      language pathology is described. In 2006, 40 students participated in a daylong
      learning experience. The first part of the experience consisted of presentations
      and discussions of different scenarios of interpersonal difficulty. The
      theoretical introduction was followed by an active learning experience with
      simulated patients. A similar experience without the simulated patients was
      conducted for 45 students in 2010. Both years of students rated the experience
      with an overall grade and gave qualitative feedback. There was no significant
      difference between the overall grades given by the students in 2006 and 2010. The
      qualitative feedback indicated that the students valued the experience and that
      they felt it added to their learning and professional development. The students
      in 2006 also provided detailed feedback on the simulation activities. Students
      endorsed the experience and recommended that the learning experience be repeated
      for future students. However, the students in 2006 also commented that they had
      felt inadequately prepared for interacting with the simulated patients. A
      learning experience with simulated patients can add to students' learning. The
      inclusion of simulated patients can provide a different, but not automatically
      better, learning experience.

PMID- 22390747
TI  - Motivating factors influencing choice of major in undergraduates in communication
      sciences and disorders.
AB  - The purposes of this study were to determine: (1) whether background factors
      influence the choice of Communication Sciences and Disorders (CSD) as an academic
      major; (2) what motivates students to major in CSD; (3) the relationship between
      motivation to pursue CSD as a major and the attractiveness of the major; and (4)
      whether motivation influences the perceived value of a career in CSD. A survey of
      143 undergraduates was created and administered to assess motivational factors
      that influence the choice of major. The participants had diverse ethnic/racial
      and cultural backgrounds and were enrolled in CSD courses in the Liberal Arts
      College of St John's University, a US American Institution in Queens, New York.
      Preliminary analyses indicated that ethnic/racial background and family income
      had no statistically significant relationship to motivations, attractiveness of
      CSD as a major, or career value of CSD as a major. Students scored highest on
      Intrinsic motivation factor (e.g., enjoy interacting with people) and the lowest
      on Science motivation (e.g., interested in science). Student confidence (e.g., in
      reaching career goals) was an important predictor in the perception of the career
      value of a CSD. Results of this study provide further insight into curriculum
      development and recruiting strategies.

PMID- 22390749
TI  - Vitiligo exacerbated after herpes zoster.

PMID- 22390748
TI  - Evolution of the osteoblast: skeletogenesis in gar and zebrafish.
AB  - BACKGROUND: Although the vertebrate skeleton arose in the sea 500 million years
      ago, our understanding of the molecular fingerprints of chondrocytes and
      osteoblasts may be biased because it is informed mainly by research on land
      animals. In fact, the molecular fingerprint of teleost osteoblasts differs in key
      ways from that of tetrapods, but we do not know the origin of these novel gene
      functions. They either arose as neofunctionalization events after the teleost
      genome duplication (TGD), or they represent preserved ancestral functions that
      pre-date the TGD. Here, we provide evolutionary perspective to the molecular
      fingerprints of skeletal cells and assess the role of genome duplication in
      generating novel gene functions. We compared the molecular fingerprints of
      skeletogenic cells in two ray-finned fish: zebrafish (Danio rerio)--a teleost-
      and the spotted gar (Lepisosteus oculatus)--a "living fossil" representative of a
      lineage that diverged from the teleost lineage prior to the TGD (i.e., the
      teleost sister group). We analyzed developing embryos for expression of the
      structural collagen genes col1a2, col2a1, col10a1, and col11a2 in well-formed
      cartilage and bone, and studied expression of skeletal regulators, including the
      transcription factor genes sox9 and runx2, during mesenchymal condensation.
      RESULTS: Results provided no evidence for the evolution of novel functions among
      gene duplicates in zebrafish compared to the gar outgroup, but our findings shed
      light on the evolution of the osteoblast. Zebrafish and gar chondrocytes both
      expressed col10a1 as they matured, but both species' osteoblasts also expressed
      col10a1, which tetrapod osteoblasts do not express. This novel finding, along
      with sox9 and col2a1 expression in developing osteoblasts of both zebrafish and
      gar, demonstrates that osteoblasts of both a teleost and a basally diverging ray
      fin fish express components of the supposed chondrocyte molecular fingerprint.
      CONCLUSIONS: Our surprising finding that the "chondrogenic" transcription factor
      sox9 is expressed in developing osteoblasts of both zebrafish and gar can help
      explain the expression of chondrocyte genes in osteoblasts of ray-finned fish.
      More broadly, our data suggest that the molecular fingerprint of the osteoblast,
      which largely is constrained among land animals, was not fixed during early
      vertebrate evolution.

PMID- 22390750
TI  - Endoscopic snare resection of bladder tumors: evaluation of an alternative
      technique for bladder tumor resection.
AB  - Transurethral resection of bladder tumor (TURBT) is the standard of care for
      initial bladder tumor management. In response to its shortcomings, we propose an
      alternative technique for tumor resection and retrieval: The endoscopic snare
      resection of bladder tumor (ESRBT). Eleven tumors managed by ESRBT were reviewed
      retrospectively. Via cystoscopy, tumors were resected en bloc with an
      electrosurgical polypectomy snare and retrieved transurethrally. Safety and
      efficacy were assessed by clinical and pathologic outcomes. ESRBT was highly
      effective for appropriate tumors. Tumor size and location varied: Two small, six
      medium, three large; six lateral wall, two dome, two trigone, one posterior wall.
      Half of initial urothelial carcinoma specimens contained muscle. There were no
      intraoperative or postoperative complications (mean follow-up: 17 mos; range 10
      25 mos). ESRBT is a feasible technique for the resection of pedunculated bladder
      tumors. It offers evident and theoretical advantages over TURBT and may augment
      bladder tumor management. Further study is needed.

PMID- 22390751
TI  - Simultaneous determination of human Enterovirus 71 and Coxsackievirus B3 by dual
      color quantum dots and homogeneous immunoassay.
AB  - Human Enterovirus 71 (EV71) and Coxsackievirus B3 (CVB3) have high risks for
      morbidity and mortality. A virus quantitation immunoassay has been proposed by
      employing two colored quantum dots (QDs), antibodies of the virus, and graphene
      oxide (GO). The QDs are streptavidin-conjugated quantum dots (SA-QDs), and the
      antibodies are biotinylated antibodies. Biotinylated EV71 antibody (Ab1) was
      associated with 525 nm green colored SA-QDs via biotin-streptavidin interaction
      forming QDs-Ab1, whereas biotinylated CVB3 antibody (Ab2) was associated with 605
      nm red colored SA-QDs via biotin-streptavidin interaction forming QDs-Ab2. GO was
      an excellent quencher to the fluorescence of both QDs-Ab1 and QDs-Ab2. The
      targets of EV71 and CVB3 can break up the complex of QDs-Ab and GO, recovering
      the fluorescence of QDs-Ab1 and QDs-Ab2, respectively. Using these two different
      colored QDs-Ab fluorescence recovery intensities upon the addition of targets
      EV71 and CVB3, the two enteroviruses can be simultaneously quantitatively
      determined with a single excitation light. The detection limits of EV71 and CVB3
      are 0.42 and 0.39 ng mL(-1) based on 3 times signal-to-noise ratio, respectively.
      More importantly, this strategy can be further used as a universal method for any
      protein or virus determination by changing the conjugated antibodies in disease
      early diagnosis, which can provide a fast and promising clinical approach for
      virus differentiation and determination. In a word, a simple, fast, sensitive,
      and highly selective assay for EV71 and CVB3 has been developed. It could be
      applied in clinical sample analysis with a satisfactory result. It was notable
      that the sensor could not only achieve rapid and precise quantitative
      determination of protein/virus by fluorescent intensity but also could be applied
      in semiquantitative protein/virus determination by digital visualization.

PMID- 22390752
TI  - Identity, influence, and change: rediscovering John Turner's vision for social
      psychology.
AB  - John Turner, whose pioneering work on social identity and self-categorization
      theories changed the face of modern social psychology, died in July 2011. This
      unique virtual special issue celebrates Turner's life and work by reproducing a
      number of key articles that were published in the British Journal of Social
      Psychology and the European Journal of Social Psychology over the course of his
      career. These articles are of three types: first, key position papers, on which
      Turner was the leading or sole author; second, papers that he published with
      collaborators (typically PhD students) that explored key theoretical
      propositions; third, short commentary papers, in which Turner engaged in debate
      around key issues within social psychology. Together, these papers map out a
      clear and compelling vision. This seeks to explain the distinctly social nature
      of the human mind by showing how all important forms of social behaviour - and in
      particular, the propensity for social influence and social change -are grounded
      in the sense of social identity that people derive from their group memberships.
      As we discuss in this editorial, Turner's great contribution was to formalize
      this understanding in terms of testable hypotheses and generative theory and then
      to work intensively but imaginatively with others to take this vision forward.

PMID- 22390753
TI  - Triaging women with ovarian masses for surgery: observational diagnostic study to
      compare RCOG guidelines with an International Ovarian Tumour Analysis (IOTA)
      group protocol.
AB  - OBJECTIVE: To compare guidelines from the Royal College of Obstetricians and
      Gynaecologists (RCOG) based on the Risk of Malignancy Index (RMI) with a protocol
      based on logistic regression model LR2 developed by the International Ovarian
      Tumour Analysis (IOTA) group for triaging women with an ovarian mass as low,
      moderate, or high risk of malignancy. DESIGN AND SETTING: Observational
      diagnostic study conducted between 2005 and 2007 at 21 oncology referral centres,
      referral centres for ultrasonography and general hospitals. SAMPLE: In all, 1938
      women undergoing surgery for an ovarian mass. METHODS: RCOG guidelines use the
      RMI to triage women as low (RMI < 25), moderate (25-250), or high (above >250)
      risk. The IOTA protocol uses LR2s estimated probability of malignancy (<0.05
      indicates low risk, >= 0.05 but <0.25 moderate risk, and >= 0.25 high risk). MAIN
      OUTCOME MEASURE: Percentages of benign, borderline and invasive tumours
      classified as low, moderate or high risk. RESULTS: The IOTA and RCOG protocols
      classified 71.1% and 62.1% of benign tumours as low risk, respectively
      (difference 9.0; 95% CI 6.2-11.9, P < 0.0001). Of invasive tumours, 88.6% and
      73.6% were labelled high risk (difference 15.0; 10.6-19.4, P < 0.0001), and 3.0%
      and 5.2% were labelled low risk (difference -2.2; -4.6 to 0.2, P = 0.07)
      respectively by each protocol. Similar results were found after stratification
      for menopausal status. CONCLUSIONS: The IOTA protocol was more accurate for
      triage than the RCOG protocol. The IOTA protocol would avoid major surgery for
      more women with benign tumours while still appropriately referring more women
      with an invasive tumour to a gynaecological oncologist.

PMID- 22390754
TI  - Targeting molecular pathways in human malignancy: current status and future
      development.

PMID- 22390755
TI  - Targeting the EGFR-family for therapy: biological challenges and clinical
      perspective.
AB  - Members of epidermal growth factor receptor (EGFR) or ErbB receptor family play a
      critical role in a wide range of human cancers. In the past decade, there has
      been a remarkable progress in developing ErbB targeted therapeutics. However, a
      substantial portion of patients has non-responsive disease or subsequently shows
      evidence of tumour relapse following initial success with anti-ErbB agents.
      Improved insights into the biology of ErbB receptor family have led to more
      effective second- and third-generation anti-ErbB therapies. In this review, we
      have summarised salient features of the ErbB receptor physiology and highlighted
      key mechanisms involved in abnormal ErbB signalling in tumorigenesis. The
      rationale of anti-ErbB receptor therapies are outlined along with key mechanisms
      proposed for resistance to treatment as well as the current concept of combined
      anti-ErbB therapies. In conclusion, improved understanding of the molecular
      pathways that confer resistance to anti-ErbB therapeutics will be essential in
      minimising tumour resistance to ErbB targeted treatments.

PMID- 22390756
TI  - Anti-VEGF strategies - from antibodies to tyrosine kinase inhibitors: background
      and clinical development in human cancer.
AB  - Tumour angiogenesis (formation of new blood vessels supporting tumour growth and
      metastasis) is a result of complex interactions between the tumour and the
      surrounding microenvironment. Targeting tumours with anti-angiogenic therapy
      remains an exciting area of preclinical and clinical studies. Although many
      significant advances have been achieved and the clinical use of anti-angiogenic
      drugs is now well recognized in many solid malignancies, these therapies fall
      short of their anticipated clinical benefits and leave many unanswered questions
      like exact mechanism of action, patients' selection and monitoring response to
      anti-angiogenic drugs. Tumour angiogenesis is controlled by complex signaling
      cascades and ongoing research into molecular mechanisms of tumour angiogenesis
      not only helps to understand its basic mechanisms but hopefully will identify new
      therapeutic targets. In 2012, both monoclonal antibodies and small molecule
      tyrosine kinase inhibitors remain the two major clinically useful therapeutic
      options that interfere with tumour angiogenesis in many solid malignancies.

PMID- 22390758
TI  - Novel VEGF-independent strategies targeting tumor vasculature: clinical aspects.
AB  - In the last decades, the active research in the field of tumor angiogenesis has
      led to the development of a class of agents providing an effective inhibition of
      neo-vessel formation through the blockade of VEGF related pathways. More
      recently, the identification of other factors involved in tumor angiogenesis,
      such as platelet-derived growth factor, fibroblast growth factor and
      Angiopoietins has emphasized the need to develop agents targeting multiple pro
      angiogenic pathways. Although contrasting data are currently available regarding
      the clinical efficacy of multikinase inhibitors, Sunitinib, Sorafenib and
      Pazopanib have displayed encouraging results, and have fuelled further
      evaluations. Moreover, definitive data are also eagerly awaited regarding the
      clinical role of angiopoietins inhibitors. On the other hand, the existence of
      morphological, functional and architectural differences between normal and tumor
      vasculature has provided solid basis for the development of a novel class of
      compounds, known as Vascular Disrupting Agents (VDAs) able to selectively disrupt
      existing tumor vessels. After initial concerns related to the potential
      development of severe cardiovascular toxicities, further clinical investigations
      have shown a safe toxicity profile for these agents. Moreover, despite the
      discouraging data on dolostatin-10 and ASA404, several VDAs, including CAP4,
      Ombrabulin and Pinabulin have already shown promising activity in phase I-II
      clinical trials warranting more advanced evaluations. In this review we aimed at
      summarizing the most relevant VEGF-independent strategies targeting tumor
      vasculature, focusing on the clinical development of novel antiangiogenic agents
      including multikinase and angiopoietins inhibitors as well as VDAs.

PMID- 22390759
TI  - The endothelin axis as therapeutic target in human malignancies: present and
      future.
AB  - To assure their growth advantage cancer cells require the appropriation of key
      pathways, such as those controlled by G-protein coupled receptor (GPCR), that
      influence cell growth, migration, and death, as well as the expansion of vascular
      networks. Accumulating molecular and in vivo evidences demonstrate that the
      activation of the endothelin-1 (ET-1) axis elicites pleiotropic effects on tumour
      cells and on the tumour microenvironment as well, modulating epithelial to
      mesenchymal transition, chemoresistance, and other tumourassociated processes. As
      ET-1 axis blockade has been shown to reduce tumor growth in preclinical models,
      several small molecule antagonists of ET-1 receptors are currently undergoing
      clinical trial as novel agents in cancer therapy. To fully appreciate the
      potential hegemony of the ET-1 axis in cancer, here we review emerging
      preclinical and clinical data outlining the spectrum of cellular activities
      triggered by ET-1 signaling and the challenges facing molecular targeted therapy.
      Because scaffold proteins, such as beta-arrestin, create signalling platforms
      that drive cellular transformation upon GPCR activation, mechanisms mediated by
      beta-arrestin in ET-1 signalling are discussed. Deeper understanding of molecular
      mechanisms activated by ET-1 receptor, as well as of how pathway crosstalk can
      influence ET-1 signalling outcome in cancer, is of paramount translational
      relevance in the study of ET-1 receptor-targeted therapy. The improved knowledge
      of the interconnected molecular mechanism promoted by ET-1 axis in cancer will
      certainly result in more effective and durable mechanism-guided combinations of
      ET-1 receptor antagonists with cytotoxic drugs or other targeted agents in the
      clinical management of ET-1 axis-dependent malignancies.

PMID- 22390757
TI  - Moving beyond VEGF for anti-angiogenesis strategies in gynecologic cancer.
AB  - Gynecologic cancer is a major burden in both developed and developing countries.
      Almost a half million deaths from gynecologic cancer are reported each year.
      Understanding the molecular biology of cancer is a principle resource leading to
      the identification of new potential therapeutic targets, which may be parlayed
      into novel therapeutic options in gynecologic cancer. Focal adhesion kinase (FAK)
      is a non-receptor tyrosine kinase, which plays a pivotal role in many aspects of
      malignant growth including cancer cell survival, migration, invasion,
      angiogenesis and metastasis. Various human cancer tissues have demonstrated high
      expression of FAK or activated FAK, which has been correlated with survival of
      cancer patients. Among gynecologic cancers, reports have emerged demonstrating
      that FAK is involved in the pathogenesis of ovarian, endometrial, and cervical
      cancers. In addition, the polycomb group protein enhancer of Zeste homologue 2
      (EZH2), Dll4/notch and EphA2 has also emerged as important regulators of
      endothelial cell biology and angiogenesis. Herein, we review the role of these
      new targets in tumor angiogenesis and the rationale for further clinical
      development.

PMID- 22390760
TI  - Estrogen receptor beta in cancer: an attractive target for therapy.
AB  - While it is well documented that the mitogenic actions of estrogens are critical
      in the development and progression of human breast and some gynecologic cancers,
      only latest data demonstrate a crucial involvement of estrogen-signaling in the
      carcinogenesis of non-classical estrogen target tissues, as colon, prostate,
      lung, skin, and brain. Only recently it has also been found out that the
      biological effects of estrogens are mediated by two distinct estrogen receptors
      (ERs), ERalpha and ERbeta, and that their relative levels in a given cell are
      important determinants of response to estradiol and selective estrogen receptor
      modulators. Indeed, although ERalpha and ERbeta have similar structure, they
      produce different effects, and there is currently increasing evidence that, for
      some tumors, an imbalanced ERbeta expression might play a pivotal role in tumor
      development and progression. However, the prognostic value, the potential
      significance in predicting response to endocrine therapy, and, eventually, the
      utility of ERbeta as a therapeutic target need to be assessed in large-scale and
      prospective clinical studies. This review examines the experimental and clinical
      evidences for a role of ERbeta in carcinogenesis of classical and nonclassical
      estrogen target tissues. If anomalies of ERbeta expression could be demonstrated
      to represent a critical step in the development and progression of some types of
      cancers, its re-expression by genetic engineering, as well as the use of targeted
      ERbeta therapies would constitute new important therapeutic approaches.

PMID- 22390761
TI  - The role of FLT3 kinase as an AML therapy target.
AB  - FMS-like tyrosine kinase-3 (FLT3) is a tyrosine kinase receptor involved in the
      survival and expansion of hematopoietic stem progenitors. A constitutively
      activated, mutated form of FLT3, is expressed in approximately 30% of de novo
      acute myeloid leukemia (AML) and about 6% of acute lymphoblastic leukemia (ALL)
      cases. Since mutant FLT3 has emerged as an attractive therapeutic target, there
      are several FLT3 inhibitors currently undergoing evaluation in different phases
      of clinical trials. However, although many aspects of the intracellular signaling
      mediated by oncogenic FLT3 have been revealed, what is the best strategy to
      inhibit FLT3 and how FLT3 inhibitors should be developed for AML treatment is
      poorly defined. Despite promising in vitro studies, where most FLT3 inhibitors
      show potent efficacy at nanomolar concentrations, clinical responses in AML
      patients are moderate and temporary. Furthermore, under prolonged therapy, FLT3
      mutation-positive leukemic cells rapidly develop resistance to FLT3 inhibitors
      when used as monotherapy. Considering that there is no uniform mechanism of
      resistance triggered by FLT3 inhibitors, it will be necessary to develop new
      agents that target FLT3, and that can be used consecutively or in combination
      with conventional cytotoxic therapeutics. On the other hand, given that
      overexpression of FLT3 ligand (FL), occurring after myelosuppressive therapy,
      reduces the efficacy of FLT3 inhibitors, targeting both FL and FLT3 kinase, might
      be more effective approach in AML treatment. Here, we summarize up-to-date
      studies on FLT3 structure, its mutation status and role in malignant signal
      trafficking. We also review why FLT3 targeted therapies have not revolutionized
      AML treatment.

PMID- 22390762
TI  - Tubulins as therapeutic targets in cancer: from bench to bedside.
AB  - Tubulin is the target of some of the most widely used and time-honored anticancer
      tubulin-binding agents (TBAs). The clinical usefulness of many TBAs has been held
      back as a result of tumor cell drug-resistance. The elucidation of the three
      dimensional structure of alphabeta-tubulin dimer has provided an opportunity for
      rational drug design aimed at generating compounds that will target tubulin in
      therapeutically more efficacious ways compared to presently available drugs. An
      issue to be addressed is which one(s) of the tubulin species, their isotypes, or
      their posttranslationally modified forms, should be specifically targeted in
      cancer chemotherapy. This review offers a critical appraisal of current knowledge
      on tubulins in cancer and an update on new anti-neoplastic microtubule-targeted
      treatment strategies. Specifically, it examines, across disciplines,
      cellular/molecular, biochemical, clinical/pathological, and pharmacological
      aspects of beta-tubulin isotypes, posttranslational modifications of tubulin
      dimers, gamma-tubulin and microtubule nucleation, and microtubule regulatory
      proteins. Emphasis is placed on the overexpression of (i) the betaIII isotype,
      which functions as a survival factor associated with dynamic instability of
      microtubules; (ii) gamma-tubulin, a key microtubule nucleating protein; and (iii)
      the microtubule severing enzyme spastin, involved in cell motility and
      proliferation of glioblastoma cells. The role of betaIII-tubulin in resistance of
      cancer cells to taxanes is examined. Attention is called to the novel concept
      that betaIII-tubulin functions as a "gateway" for prosurvival signals in
      partnership with GTPases, such as GBP1. Appraisal is also offered on epothilones
      and the concept of hypersensitization to TBAs as promising therapeutic strategies
      in taxane resistant epithelial cancers and in high-grade gliomas.

PMID- 22390763
TI  - Novel drugs targeting microtubules: the role of epothilones.
AB  - Among the drugs targeting microtubule functions by interfering with tubulin
      subunits, epothilones represent a class of anticancer agents which recently
      entered clinical development. Although epothilones share mechanisms of action
      similar to taxanes, they have non-overlapping mechanisms of resistance; in
      particular, while overexpression of class III beta-tubulin plays a major role in
      taxane resistance, epothilones display their highest efficacy in class III beta
      tubulin overexpressing malignancies. Three compounds belonging to this family
      (patupilone, ixabepilone and sagopilone), have been actively investigated in
      clinical trials, and some of them are at an advanced stage of development. This
      review provides a comprehensive analysis of the available literature on
      epothilones, focusing on their clinical development and potential as an
      additional weapon in the arsenal against tumors.

PMID- 22390764
TI  - Approaches for developing novel microtubule targeting agents (MTAs) for
      therapeutic exploitation.
AB  - The microtubule (MT) represents a highly validated target for therapy. Insights
      into the complex nature of the dynamic microtubule physiology will provide the
      basis for developing novel microtubule targeting agents with enhanced efficacy
      and minimised toxicity. In this article, with an emphasis on translational
      applications, we have summarised relevant aspects of tubulin physiology in the
      context of developing MT binding agents as therapeutic agents. Case studies were
      included to illustrate therapeutic developments in prostate cancer and current
      strategies to discover novel agents or targets for therapy.

PMID- 22390765
TI  - Molecular targets of gemcitabine action: rationale for development of novel drugs
      and drug combinations.
AB  - Gemcitabine is one of the most widely used pyrimidine analogues, with a well
      established role as a first- and second-line treatment of several types of
      tumors. Several preclinical and clinical studies have been done to obtain
      information on molecular determinants of gemcitabine activity and metabolism, in
      order to predict whether this drug will be effective and safe for the individual
      patient. Among these molecular determinants, the mRNA and protein expression of
      equilibrative transporter-1 (ENT1) and ribonucleotide reductase (RR) emerged as
      possible predictors of drug activity in studies on pancreatic and non-small cell
      lung cancer. However, cytidine deaminase polymorphisms and activity were
      correlated with clinical outcome and severe toxicities, whereas further studies
      should evaluate both P53 dependent and independent pathways involved in
      gemcitabine induced apoptosis. Improved knowledge on these determinants is
      critical for the optimal development of combination of gemcitabine with other
      conventional or biological therapies, as well as to exploit the radiosensitizing
      potential of gemcitabine. Emerging technologies such as massive parallel
      sequencing, gene expression arrays and proteomics may identify novel biomarkers
      in tumor material, while polymorphisms and phenotyping analysis should unravel
      factors involved in drug toxicity. Validation of these markers in preclinical
      models should be used for the appropriate patient enrolment into subsequent
      prospective studies. Hopefully, novel pharmacogenetic biomarkers will be
      validated in these prospective studies and used to select cancer patients to be
      treated with gemcitabine-based regimens in the near future or to enroll them in
      studies with prodrugs in order to bypass resistance mechanisms.

PMID- 22390766
TI  - Chemoradiotherapy of human tumors: novel approaches from nanomedicine.
AB  - Chemoradiotherapy is an important treatment paradigm in oncology and is part of
      the curative treatment for many solid cancers, such as lung, pancreatic and
      cervical cancers. One of the main goals in oncology research is to develop
      approaches that can improve the efficacy of chemoradiotherapy while minimizing
      treatment toxicity. A new and exciting approach is to incorporate advances in
      nanomedicine into chemoradiotherapy. Nanoparticles possess unique properties,
      such as preferential accumulation in tumors and minimal uptake in normal tissues,
      that make them ideally suited for delivering chemotherapy in chemoradiotherapy.
      In this review, we plan to discuss the rationale and evidence for applying
      nanomedicine to chemoradiotherapy.

PMID- 22390767
TI  - Cancer stem cells and novel targets for antitumor strategies.
AB  - Cancer stem cells (CSCs) were identified in human leukemias in landmark studies
      of John Dick and his colleagues. Subsequently, similar cancer stem-like cells
      were identified in solid tumors of the breast, colon, brain and other sites. CSCs
      have distinct markers and are highly tumorigenic compared to other subsets. They
      can differentiate into all the cell phenotypes of the parental tumor. Other key
      features include activation of pluripotency genes (Oct4, Sox2, Nanog), self
      renewal, formation of tumor spheres in low-adherence cultures, and multi-drug
      resistance. Clinically, drug resistance is probably the most important feature,
      because CSCs resist conventional cancer therapies and are likely to play a major
      role in cancer relapse. Based on their properties, several molecules have been
      targeted for therapy with drugs as follows. 1) The self-renewal pathways Wnt/beta
      catenin, Hedgehog and Notch. 2) The aryl hydrocarbon receptor (AHR), with
      tranilast and other AHR agonists. 3) Cytokines and inflammatory pathways (e.g.,
      IL-6, IL-8, NF-kappaB). 4) TGF-beta and epithelial- to-mesenchymal transition
      (EMT) pathways. 5) Homing molecules involved in metastasis; most notably CXCR4 or
      its ligand CXCL12. 6) Growth factors, their receptors and coreceptors (such as
      neuropilin-1), and signaling components (e.g., tyrosine kinases). 7) Cell-surface
      markers (CD44 and integrins). Several drugs have been identified by screening or
      other observations (salinomycin, metformin, tesmilifene, sulforaphane, curcumin,
      piperine and others). Some of these drugs are at preclinical or early clinical
      phases of development, and it remains to be seen how many will progress to
      clinical application. This review focuses on some promising new developments in
      anti-CSC drug therapy.

PMID- 22390769
TI  - Construction of C(aryl)-C(alkynyl) bond from copper-mediated arene-alkyne and
      aryl iodide-alkyne cross-coupling reactions: a common aryl-Cu(III) intermediate
      in arene C-H activation and Castro-Stephens reaction.
AB  - Both copper(II)-mediated oxidative C-H bond activation and oxidative addition of
      copper(I) into a C-I bond produced an identical and structurally well-defined
      aryl-Cu(III) intermediate. The cross-coupling reaction of an aryl-Cu(III)
      intermediate with both terminal alkynes at an elevated temperature and
      alkynyllithium reagents under mild conditions led effectively to the formation of
      a C(aryl)-C(alkynyl) bond. An alternative mechanism has been proposed for the
      Castro-Stephens reaction.

PMID- 22390770
TI  - Healthcare utilization among patients with depression before and after initiating
      duloxetine in the United Kingdom.
AB  - OBJECTIVE: Duloxetine is indicated for treatment of major depressive disorders in
      the UK. While clinical trials have documented its clinical effectiveness, little
      is known regarding the relationship between duloxetine use and healthcare
      utilization in community practice. This study quantifies the impact of treatment
      with duloxetine on healthcare utilization among patients with depression and
      those with depression and co-existing pain. METHODS: Depressed adults initiating
      duloxetine during 1/1/2006-9/30/2007 were identified from the General Practice
      Research Database (GPRD). All-cause hospitalization, accident/emergency visits,
      specialist referrals, and analgesic use in the 12 months before (pre-period) and
      after (post-period) duloxetine initiation were compared. Generalized Estimating
      Equation models evaluated the pre-post change in the odds of hospitalization.
      RESULTS: Nine hundred and nine patients were identified, 413 had pre-period
      unexplained pain (UPain). Rates of hospitalization declined from the pre- to the
      post-period. Fewer UPain patients received analgesics post-duloxetine initiation.
      Multivariate analyses confirmed that the odds of hospitalization were lower after
      duloxetine initiation. UPain patients with pre-period anticonvulsant use had
      lower odds of hospitalization in the post-period and the reduction in odds was
      significantly larger than that of patients without pre-period anticonvulsants.
      While patients with pre-period anxiolytic use, alcohol/drug dependence, or sleep
      disorders did not show statistically significant pre-post change in the odds of
      hospitalization, these changes were significantly different from patients without
      these conditions. LIMITATIONS: The study did not include a comparison group of
      patients who were non-users of duloxetine. Prevalence of chronic conditions might
      be under-estimated due to coding in the GPRD. Medications were assumed to be
      taken as prescribed. Study results are not generalizable beyond the population
      covered by the UK's primary care system. CONCLUSIONS: All-cause hospitalization
      rates lowered among depressed patients and fewer UPain patients received
      analgesics post-duloxetine initiation. The reduction in the odds of
      hospitalization was most pronounced among UPain patients receiving pre-period
      anticonvulsants.

PMID- 22390771
TI  - AutoMate ExpressTM forensic DNA extraction system for the extraction of genomic
      DNA from biological samples.
AB  - The AutoMate ExpressTM Forensic DNA Extraction System was developed for automatic
      isolation of DNA from a variety of forensic biological samples. The performance
      of the system was investigated using a wide range of biological samples.
      Depending on the sample type, either PrepFilerTM lysis buffer or PrepFiler BTATM
      lysis buffer was used to lyse the samples. After lysis and removal of the
      substrate using LySepTM column, the lysate in the sample tubes were loaded onto
      AutoMate ExpressTM instrument and DNA was extracted using one of the two
      instrument extraction protocols. Our study showed that DNA was recovered from as
      little as 0.025 MUL of blood. DNA extracted from casework-type samples was free
      of detectable PCR inhibitors and the short tandem repeat profiles were complete,
      conclusive, and devoid of any PCR artifacts. The system also showed consistent
      performance from day-to-day operation.

PMID- 22390772
TI  - Klebsiella pneumoniae resistant to third-generation cephalosporins in five
      African and two Vietnamese major towns: multiclonal population structure with two
      major international clonal groups, CG15 and CG258.
AB  - The molecular epidemiology of third-generation cephalosporin-resistant (3GC-R)
      Klebsiella pneumoniae in developing countries is poorly documented. From February
      2007 to March 2008, we collected 135 3GC-R K. pneumoniae isolates from seven
      major towns in Maghreb (Morocco), West Africa (Senegal, Cote d'Ivoire), Central
      Africa (Cameroon), East Africa (Madagascar) and Southeast Asia (Vietnam). Their
      genetic diversity, assessed by multilocus sequence typing, was high (60 sequence
      types), reflecting multiclonality. However, two major clonal groups, CG15 (n =
      23, 17% of isolates) and CG258 (n = 18, 13%), were detected in almost all
      participating centres. The two major clonal groups have previously been described
      in other parts of the world, indicating their global spread. The high diversity
      of enterobacterial repetitive intergenic consensus sequence-PCR banding patterns
      at the local level indicates that most isolates were epidemiologically unrelated.
      The isolates were characterized by the presence of multiple resistance
      determinants, most notably the concomitant presence of the aac(6')-Ib-cr, qnr and
      blaCTX-M-15 genes in 61 isolates (45%) belonging to 31 sequence types. These
      isolates were detected across a large geographical area including Cameroon (n =
      1), Vietnam (n = 4), Madagascar (n = 10), Cote d'Ivoire (n = 12), Morocco (n =
      13) and Senegal (n = 21). These results have major implications for patient
      management and highlight a potential reservoir for resistance determinants.

PMID- 22390774
TI  - Droplet compression and relaxation by a superhydrophobic surface: contact angle
      hysteresis.
AB  - In this article, the contact angle hysteresis (CAH) of acrylic glass is
      experimentally and theoretically studied through the compression-relaxation
      process of droplets by using a superhydrophobic surface with negligible CAH
      effect. In contrast to the existing technique in which the volume of the droplet
      changes during the measurement of CAH, this procedure is carried out at a
      constant volume of the droplet. By observing the base diameter (BD) and the
      contact angle (CA) of the droplet during the compression-relaxation process, the
      wetting behavior of the droplet can be divided into two regimes, the contact line
      withdrawal and the contact line pinning regimes, depending on the gap thickness
      (H) at the end of the compression process. During the compression process, both
      regimes possess similar droplet behavior; the contact line will move outward and
      the BD will expand while the CA remains at the advancing angle. During the
      relaxation process, the two regimes are significantly different. In the contact
      line withdrawal regime, the contact line will withdraw with the CA remaining at
      the receding angle. In the contact line pinning regime, however, the contact line
      will be pinned at the final position and the CA will decline to a certain value
      higher than the receding angle. Furthermore, the advancing pinning behavior can
      also be realized through a successive compression-relaxation process. On the
      basis of the liquid-induced defects model, Surface Evolver simulations are
      performed to reproduce the behavior of the droplet during the compression
      relaxation process; both contact line withdrawal and pinning regimes can also be
      identified. The results of the experiment and simulation agree with each other
      very well.

PMID- 22390773
TI  - A view to kill.
AB  - Genome and proteome data from Hydra magnipapillata have opened the way for the
      molecular analysis of an ancient nervous system, which includes stinging cells,
      an unusual neurosensory and neurosecretory cell type. They hold some surprises
      for the mechanisms and evolution of sensory transduction that could not have been
      anticipated from what has been learned from flies and vertebrates. Research in
      BMC Biology now implicates the ancient opsin-mediated transduction pathway in the
      neuronal control of stinging cell discharge.

PMID- 22390776
TI  - Arginine metabolism is markedly impaired in polymicrobial infected mice.

PMID- 22390775
TI  - Structure of the S. aureus PI-specific phospholipase C reveals modulation of
      active site access by a titratable pi-cation latched loop.
AB  - Staphylococcus aureus secretes a phosphatidylinositol-specific phospholipase C
      (PI-PLC) as a virulence factor that is unusual in exhibiting higher activity at
      acidic pH values than other enzymes in this class. We have determined the crystal
      structure of this enzyme at pH 4.6 and pH 7.5. Under slightly basic conditions,
      the S. aureus PI-PLC structure closely follows the conformation of other
      bacterial PI-PLCs. However, when crystallized under acidic conditions, a large
      section of mobile loop at the alphabeta-barrel rim in the vicinity of the active
      site shows ~10 A shift. This loop displacement at acidic pH is the result of a
      titratable intramolecular pi-cation interaction between His258 and Phe249. This
      was verified by a structure of the mutant protein H258Y crystallized at pH 4.6,
      which does not exhibit the large loop shift. The intramolecular pi-cation
      interaction for S. aureus PI-PLC provides an explanation for the activity of the
      enzyme at acid pH and also suggests how phosphatidylcholine, as a competitor for
      Phe249, may kinetically activate this enzyme.

PMID- 22390777
TI  - Dead space and CO2 elimination related to pattern of inspiratory gas delivery in
      ARDS patients.
AB  - INTRODUCTION: The inspiratory flow pattern influences CO2 elimination by
      affecting the time the tidal volume remains resident in alveoli. This time is
      expressed in terms of mean distribution time (MDT), which is the time available
      for distribution and diffusion of inspired tidal gas within resident alveolar
      gas. In healthy and sick pigs, abrupt cessation of inspiratory flow (that is,
      high end-inspiratory flow (EIF)), enhances CO2 elimination. The objective was to
      test the hypothesis that effects of inspiratory gas delivery pattern on CO2
      exchange can be comprehensively described from the effects of MDT and EIF in
      patients with acute respiratory distress syndrome (ARDS). METHODS: In a medical
      intensive care unit of a university hospital, ARDS patients were studied during
      sequences of breaths with varying inspiratory flow patterns. Patients were
      ventilated with a computer-controlled ventilator allowing single breaths to be
      modified with respect to durations of inspiratory flow and postinspiratory pause
      (TP), as well as the shape of the inspiratory flow wave. From the single-breath
      test for CO2, the volume of CO2 eliminated by each tidal breath was derived.
      RESULTS: A long MDT, caused primarily by a long TP, led to importantly enhanced
      CO2 elimination. So did a high EIF. Effects of MDT and EIF were comprehensively
      described with a simple equation. Typically, an efficient and a less-efficient
      pattern of inspiration could result in +/- 10% variation of CO2 elimination, and
      in individuals, up to 35%. CONCLUSIONS: In ARDS, CO2 elimination is importantly
      enhanced by an inspiratory flow pattern with long MDT and high EIF. An optimal
      inspiratory pattern allows a reduction of tidal volume and may be part of lung
      protective ventilation.

PMID- 22390780
TI  - Effect of administration of apoptotic blebs on disease development in lupus mice.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease
      characterised by the formation of autoantibodies against nuclear components.
      Disturbed apoptosis and reduced clearance of apoptotic material have been
      assigned a role in the pathogenesis of SLE. During apoptosis, apoptotic blebs are
      formed, in which SLE autoantigens are clustered. In vitro, apoptotic blebs can
      induce maturation of dendritic cells (DC), which in turn can stimulate IL-17
      production by T cells. Here, we investigated the effects of administration of
      apoptotic blebs, separate or in combination with dendritic cells, on disease
      progression and autoantibody production in lupus and normal mice. METHODS: A
      preparation of apoptotic blebs, with or without DC, was intravenously
      administered to MRL/lpr and CBA mice at weeks 7, 9, and 11 of age. T-cell
      responses against autoantigens present in blebs were examined by delayed type
      hypersensitivity reactions. Disease progression of the mice was evaluated by
      determining proteinuria and the titers of anti-DNA, anti-histone, and anti
      nucleosome autoantibodies in plasma. RESULTS: Repeated administration of
      apoptotic blebs, with or without DC, had no effect on the course of proteinuria
      or on anti-DNA, anti-histone and anti-nucleosome autoantibody levels in MRL/lpr
      mice. Intravenous injections of apoptotic blebs resulted in a decrease in the DTH
      response towards s.c. administered blebs in MRL/lpr mice and in reduced anti
      nucleosome antibody titers in CBA mice. These tolerizing effects were lost when
      apoptotic blebs were administered together with syngeneic DC after 2 hours of co
      incubation. DISCUSSION AND CONCLUSIONS: In contrast to previous studies with
      apoptotic cells, and deviating from our in vitro findings with apoptotic blebs,
      we observed no stimulating effect of the administration of apoptotic blebs on
      disease progression in MRL/lpr lupus mice. The tolerogenic effects that were
      observed may be associated with rapid removal of i.v. administered blebs by
      phagocytes in an immune-silencing way.

PMID- 22390778
TI  - Increased incidence of chronic lymphocytic leukaemia and lymphomas in patients
      with Merkel cell carcinoma - a population based study of 335 cases with
      neuroendocrine skin tumour.
AB  - Merkel cell carcinoma (MCC) is a rare aggressive skin tumour that appears to be
      associated with a large number of other tumours. We collected all reported cases
      in Israel and estimated its association with other tumours, including
      haematological malignancies. The population based Israel Cancer Registry
      identified 335 patients with MCC diagnosed between1989 and 2010. Ninety-seven
      percent were in the Jewish population; median age at diagnosis for Jewish
      patients was 73.4 and 55.6 years for the Arab population. Other associated
      malignancies were encountered in 92 patients (27.4%) with MCC (90 Jews, two
      Arabs). Of the Jewish cases, 66 presented with an associated malignancy before,
      and 24 after, the diagnosis of MCC. Solid tumours were not significantly
      increased among patients with MCC. Thirty-one of these associated cancers (34.4%)
      were haemato-oncological malignancies, 24 were detected before and seven after
      the diagnosis of MCC. The standardized incidence ratio (SIR) for haematological
      malignancy was 3.67 for males and 3.62 for females, and the most frequent haemato
      oncological neoplasias recorded were chronic lymphocytic leukaemia (45%) and
      lymphomas (29%). Although MCC is rare, clinicians should be aware of the possible
      association with B-cell lymphoproliferative disorders when evaluating patients
      with neuroendocrine skin tumours.

PMID- 22390781
TI  - The Turku Declaration: a consensus document on psychiatric-mental health nursing
      roles, education, and practice.

PMID- 22390784
TI  - FDA-approved drugs to treat ADHD.

PMID- 22390786
TI  - Ionic liquid salt bridge with low solubility of water and stable liquid junction
      potential based on a mixture of a potential-determining salt and a highly
      hydrophobic ionic liquid.
AB  - A new type of ionic liquid salt bridge (ILSB) based on a mixture of
      pentyltripropylammonium bis(pentafluoroethanesulfonyl)amide,
      [N(3335)(+)][C(2)C(2)N(-)], and heptadecafluorodecyltrioctylphosphonium
      tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, [TOPH(+)][TFPB(-)], shows a
      stable phase-boundary potential (Delta(IL)(W)phi) between the ILSB and an aqueous
      solution of MCl (M = H(+), Li(+), Na(+), and K(+)) over the concentration range
      from 0.05 mM to 0.5 M with an averaged excursion in 1 h of +/-0.3 mV. The
      reproducibility of Delta(IL)(W)phi is +/-0.6 mV on average (95% confidence
      interval) in KCl solutions in this concentration range. The mixing of the two
      different types of salts not only increases the stability of the phase-boundary
      potential but provides us with more freedom in selecting potential-determining
      salts to design and customize ILSBs for different purposes.

PMID- 22390787
TI  - Gait and balance in treatment-naive active alcoholics with and without a lifetime
      drug codependence.
AB  - BACKGROUND: Disturbed gait and balance are among the most consistent sequelae of
      chronic alcoholism. However, although a majority of alcoholics have never sought
      treatment, most investigations showing ataxia in alcohol-dependent individuals
      have relied on samples drawn from treated populations. In addition, few studies
      have addressed the associations of codependence on other drugs with alcoholic
      gait and balance disturbance. METHODS: This study employed the Walk-a-Line Ataxia
      Battery (Fregly et al. Alcohol Clin Exp Res 1972;43:395-399) to assess gait and
      balance in treatment-naive, actively drinking alcohol-dependent men and women
      (TNA; n = 69) who were dependent on alcohol only (ALC; n = 43), or who also had a
      lifetime drug dependence (ALC + DRG; n = 26; i.e., methamphetamine, cocaine,
      opiates, and/or marijuana), compared with nonsubstance abusing controls (NSAC; n
      = 74).We also examined associations between lifetime alcohol use and age with
      gait and balance measures. RESULTS: Our main findings were (i) no evidence of
      disturbed gait and balance in ALC versus NSAC and (ii) significantly disturbed
      gait and balance in ALC + DRG, relative to both NSAC and ALC, along with steeper
      age-associated decline in gait and balance performance in ALC versus ALC + DRG.
      CONCLUSIONS: Our results provide evidence consistent with previous studies that
      TNA (without a lifetime drug codependence) may represent a population that is
      different and less impaired (including in gait and balance) than treated
      alcoholics. Additionally, we provide evidence that ALC + DRG, with greater
      alcohol use and family drinking density than ALC, have an accelerated effect of
      age on gait and balance disturbance compared with both NSAC and ALC. The ALC +
      DRG group likely represents a subset of TNA with different characteristics than
      ALC.

PMID- 22390788
TI  - Level of oral health impacts among patients participating in PEARL: a dental
      practice-based research network.
AB  - OBJECTIVES: To determine whether participants of a dental practice-based research
      network (PBRN) differ in their level of oral health impact as measured by the
      Oral Health Impact Profile (OHIP) questionnaire. METHODS: A total of 2410
      patients contributed 2432 OHIP measurements (median age = 43 years; interquartile
      range = 28) were enrolled in four dental studies. All participants completed the
      Oral Health Impact Profile (OHIP-14) during a baseline visit. The main outcome of
      this study was the level of oral health impact, defined as follows: no impact
      ('Never' reported on all items); low ('Occasionally' or 'Hardly ever' as the
      greatest frequency score reported on any item); and high ('Fairly often' or 'Very
      often' as the greatest frequency reported on any item). Polychotomous logistic
      regression was used to develop a predictive model for the level of oral health
      impact considering the following predictors: patient's age, gender, race,
      practice location, type of dentist, and number of years the enrolling dentist has
      been practicing. RESULTS: A high level of oral health impacts was reported in 8%
      of the sample; almost a third (29%) of the sample reported a low level of
      impacts, and 63% had no oral health impacts. The prevalence of impacts differed
      significantly across protocols (P < 0.001). Women were more likely to be in the
      high oral impact group than in the no impact group compared to men (OR = 1.46;
      95% CI = 1.06-1.99). African Americans were more likely to report high oral
      impacts when compared to other racial/ethnic groups (OR = 2.11; 95% CI = 1.26
      3.55). Protective effects for being in the high or in the low-impact groups were
      observed among patients enrolled by a solo practice (P < 0.001) or by more
      experienced dentists (P = 0.01). A small but highly significant statistical
      association was obtained for patient age (P < 0.001). In the multivariate model,
      patient's age, practice size, and gender were found to jointly be significant
      predictors of oral health impact level. CONCLUSIONS: Patients' subjective report
      of oral health impact in the clinical setting is of importance for their health.
      In the context of a dental PBRN, the report of oral health-related quality of
      life (OHRQoL) was different across four dental studies. The observed findings
      validate the differential impact that oral health has on the patients' perception
      of OHRQoL particularly among specific groups. Similar investigations to elucidate
      the factors associated with patient's report of quality of life are warranted.

PMID- 22390790
TI  - Discrimination of transparent polyethylene films based on identification of
      inorganic antiblocking agents.
AB  - Several nondestructive and semidestructive analyses were used to discriminate
      colorless transparent polyethylene bags. Transparent plastic bags made from low
      density and linear low-density polyethylene usually contain antiblocking agents
      to prevent sticking of the film, which makes it difficult to open the mouths of
      plastic bags. Inorganic antiblocking agents are uniformly dispersed in
      polyethylene films, so they are easily observed using optical microscopy. The
      particle size distributions of the antiblocking agents were compared by
      statistical tests. Particle composition was examined by elemental analysis using
      energy-dispersive X-ray spectrometry with a scanning electron microscope and by
      molecular vibration analysis using a sensitive microscopic Raman spectrometer.
      The compositions could be determined nondestructively on the basis of the
      results. These data reinforce the morphological discrimination. Morphological
      discrimination of the dispersed antiblocking agent powders, statistical
      comparison of particle size distributions, and compositional analysis of the
      antiblocking agents strengthen the ability to discriminate polyethylene films.

PMID- 22390789
TI  - Suzuki coupling of potassium cyclopropyl- and alkoxymethyltrifluoroborates with
      benzyl chlorides.
AB  - Efficient Csp(3)-Csp(3) Suzuki couplings have been developed with both potassium
      cyclopropyl- and alkoxymethyltrifluoroborates. Moderate to good yields have been
      achieved in the cross-coupling of potassium cyclopropyltrifluoroborate with
      benzyl chlorides possessing electron-donating or electron-withdrawing
      substituents. Benzyl chloride was also successfully cross-coupled to potassium
      alkoxymethyltrifluoroborates derived from primary, secondary, and tertiary
      alcohols.

PMID- 22390791
TI  - Cisplatin-tethered gold nanoparticles that exhibit enhanced reproducibility, drug
      loading, and stability: a step closer to pharmaceutical approval?
AB  - Gold nanoparticles (AuNPs) can be used as delivery vehicles for platinum
      anticancer drugs, improving their targeting and uptake into cells. Here, we
      examine the appropriateness of different-sized AuNPs as components of platinum
      based drug-delivery systems, investigating their controlled synthesis,
      reproducibility, consistency of drug loading, and stability. The active component
      of cisplatin was tethered to 25, 55, and 90 nm AuNPs, with the nanoparticles
      being almost spherical in nature and demonstrating good batch-to-batch
      reproducibility (24.37 +/- 0.62, 55.2 +/- 1.75, and 89.1 +/- 2.32 nm). The size
      distribution of 25 nm AuNPs has been significantly improved, compared with a
      previous method that produces polydispersed nanoparticles. Attachment of platinum
      to the AuNP surface through a poly(ethylene glycol) (PEG) linker exhibits an
      increase in the drug loading with increasing particle size: 25 nm (815 +/- 106
      drug molecules per AuNP), 55 nm (14216 +/- 880), and 90 nm (54487 +/- 15996). The
      stability of the naked, PEGylated, and platinum-conjugated nanoparticles has been
      examined over time under various conditions. When stored at 4  degrees C, there
      is minimal variation in the diameter for all three AuNP sizes; variation after 28
      days for the 25 nm AuNPs was 2.4%; 55 nm, 3.3%; and 90 nm, 3.6%. The 25 nm AuNPs
      also demonstrate minimal changes in UV-visible absorbance over the same time
      period.

PMID- 22390792
TI  - Immunohistological analysis of in-transit metastasis in a patient with advanced
      melanoma treated with combination therapy of cytosine guanine dinucleotide
      oligodeoxynucleotide, dacarbazine and beta-interferon: a case report.

PMID- 22390793
TI  - Mutual powerlessness in client participation practices in mental health care.
AB  - BACKGROUND: Client participation has become a dominant policy goal in many
      countries including the Netherlands and is a topic much discussed in the
      literature. The success of client participation is usually measured in terms of
      the extent to which clients have a say in the participation process. Many
      articles have concluded that client participation is limited; professionals often
      still control the participation process and outcomes. OBJECTIVE: The objective of
      this study is to gain insight into (i) the practice of client participation
      within a quality improvement collaborative in mental health care and (ii) the
      consequences of a Foucauldian conceptualization of power in analysing practices
      of client participation. DESIGN: We used an ethnographic design consisting of
      observations of national events and improvement team meetings and interviews with
      the collaborative's team members and programme managers. RESULTS: Contrary to
      many studies on client participation, we found both clients and service providers
      frequently felt powerless in its practice. Professionals and clients alike
      struggled with the contributions clients could make to the improvement processes
      and what functions they should fulfil. Moreover, professionals did not want to
      exert power upon clients, but ironically just for that reason sometimes struggled
      with shaping practices of client participation. This mutual powerlessness
      (partly) disappeared when clients helped to determine and execute specific
      improvement actions instead of participating in improvement teams. CONCLUSION:
      Recognizing that power is inescapable might allow for a more substantive
      discussion concerning the consequences that power arrangements produce, rather
      than looking at who is exerting how much power.

PMID- 22390794
TI  - Cyanide is an adequate agonist of the plant hormone ethylene for studying
      signalling of sensor kinase ETR1 at the molecular level.
AB  - The plant hormone ethylene is involved in many developmental processes and
      responses to environmental stresses in plants. Although the elements of the
      signalling cascade and the receptors operating the ethylene pathway have been
      identified, a detailed understanding of the molecular processes related to signal
      perception and transfer is still lacking. Analysis of these processes using
      purified proteins in physical, structural and functional studies is complicated
      by the gaseous character of the plant hormone. In the present study, we show that
      cyanide, a pi-acceptor compound and structural analogue of ethylene, is a
      suitable substitute for the plant hormone for in vitro studies with purified
      proteins. Recombinant ethylene receptor protein ETR1 (ethylene-resistant 1)
      showed high level and selective binding of [(14)C]cyanide in the presence of
      copper, a known cofactor in ethylene binding. Replacement of Cys(65) in the
      ethylene-binding domain by serine dramatically reduced binding of radiolabelled
      cyanide. In contrast with wild-type ETR1, autokinase activity of the receptor is
      not reduced in the ETR1-C65S mutant upon addition of cyanide. Additionally,
      protein-protein interaction with the ethylene signalling protein EIN2 (ethylene
      insensitive 2) is considerably sustained by cyanide in wild-type ETR1, but is not
      affected in the mutant. Further evidence for the structural and functional
      equivalence of ethylene and cyanide is given by the fact that the ethylene
      responsive antagonist silver, which is known to allow ligand binding but prevent
      intrinsic signal transduction, also allows specific binding of cyanide, but shows
      no effect on autokinase activity and ETR1-EIN2 interaction.

PMID- 22390795
TI  - Postinfarct cardiac remodeling and the substrate for sudden cardiac death: role
      of oxidative stress and myocardial fibrosis.

PMID- 22390796
TI  - Stress-induced cardiomyopathy: a syndrome of the susceptible patient?

PMID- 22390797
TI  - Central sleep apnea treatment in heart failure: are we counting chickens before
      they are hatched?

PMID- 22390799
TI  - Real-life global survey evaluating patients with atrial fibrillation (REALISE
      AF): results of an international observational registry.
AB  - Despite being one of the most studied arrhythmias, there is paucity of
      information regarding atrial fibrillation (AF) control in the general population
      and the treatment strategies utilized by healthcare providers. REALISE-AF is an
      ongoing international registry investigating the management of AF and its control
      in nonhospitalized subjects. The registry has enrolled patients in 26 countries
      worldwide with the primary aim to determine the control of AF. This article
      presents a review of the initial results from the REALISE-AF registry and
      compares it to major practice-changing clinical trials conducted in the past. It
      also gives an overview of the current management strategies, recent updates in
      treatment and what further developments portend in the future.

PMID- 22390800
TI  - Aliskiren, amlodipine and hydrochlorothiazide triple combination for
      hypertension.
AB  - Cardiovascular-related morbidity and mortality is linked to hypertension with
      proportional gains in cardiovascular risk factor reduction with the lowering of
      blood pressure. Clinical trial data has shown that attaining goal blood pressure
      requires, for most patients, at least two antihypertensive medications, with a
      significant proportion requiring regimens of three or more medications. Single
      pill triple combinations have returned to the market following results of
      increased efficacy and adherence over dual- and mono-therapy. The combination of
      aliskiren, amlodipine and hydrochlorothiazide is a rational choice for
      combination therapy and recent studies suggest that it is safe and effective in
      lowering blood pressure in patients who fail dual combination therapy.

PMID- 22390801
TI  - Highlights of the American Heart Association Scientific Sessions 2011: a focus on
      ATLAS-TIMI 51, TRACER and PALLAS.
AB  - Several key reports from the American Heart Association meeting, held in Orlando
      (FL, USA) in November 2011, are presented related to anti-thrombotic therapy in
      acute coronary syndrome and the use of dronedarone in permanent atrial
      fibrillation is discussed in this brief (and selective) overview of this meeting.
      A summary of the ATLAS-TIMI-51, TRACER and PALLAS trials is provided.

PMID- 22390802
TI  - For a rapid diagnosis of acute myocardial infarction, a sensitive troponin assay
      is needed in the near-patient testing setting.
AB  - An early diagnosis of myocardial infarction in the emergency setting would be
      advantageous for both patients and the physicians treating these patients.
      Guidelines currently recommend serial samples that are drawn at presentation and
      6-9 h later to be measured for cardiac troponin to aid in this diagnosis.
      However, much effort has been directed to decrease the time to make a diagnosis
      in this setting, and there has been renewed interest in shortening the time
      between serial measurements as well as the turnaround time for reporting the
      results. By eliminating the blood sample transit time to the central laboratory,
      point-of-care testing or near-patient testing can reduce the turnaround time for
      reporting the results, however this is possibly at the cost of decreased
      diagnostic performance. In this article, we discuss the recent results from the
      RATPAC study, which evaluated whether the combination of myoglobin, the MB
      isoenzyme of creatine kinase (CKMB) and a sensitive troponin assay would be
      superior to troponin alone.

PMID- 22390803
TI  - Drug and device therapy for patients with chronic heart failure.
AB  - Untreated heart failure is a terminal illness with a poor prognosis. beta
      blockers are an established therapy used to reduce morbidity and mortality.
      Hypotension and bradycardia often hinder optimal beta-blocker administration in
      patients with chronic heart failure. The efficacy of cardiac resynchronization
      therapy (CRT) in affecting favorable cardiac remodeling and reducing mortality in
      heart failure patients with electrical dyssynchrony has been demonstrated in
      landmark trials only in patients receiving optimal medical therapy. This paper
      demonstrates the favorable effects of CRT on cardiac hemodynamics facilitating
      uptitration of beta-blocker therapy. It highlights the synergistic relationship
      of the two therapies and emphasizes the importance of optimizing medical therapy
      before and after CRT implantation.

PMID- 22390804
TI  - Gastroesophageal reflux and atrial fibrillation: is there any correlation?
AB  - Atrial fibrillation (AF), gastroesophageal reflux disease (GERD) and hiatal
      hernias are commonly seen in clinical practice. GERD and hiatal hernias have been
      proposed to be a possible cause of AF. In this paper, we will briefly review
      GERD, AF and hiatal hernias, consider the available literature covering the
      association between these diseases and provide further insight into the topic in
      general.

PMID- 22390805
TI  - Novel pathways and therapies in experimental diabetic atherosclerosis.
AB  - Diabetic subjects are at a greater risk of developing major vascular
      complications due to abnormalities pertinent to the diabetic milieu. Current
      treatment options achieve significant improvements in glucose levels and blood
      pressure control, but do not necessarily prevent or retard diabetes-mediated
      macrovascular disease. In this review, we highlight several pathways that are
      increasingly being appreciated as playing a significant role in diabetic vascular
      injury. We focus particularly on the advanced glycation end product/receptor for
      advanced glycation end product (AGE/RAGE) axis and its interplay with the nuclear
      protein HMGB1. We discuss evidence implicating a significant role for the renin
      angiotensin system, urotensin II and PPAR, as well as the importance of
      proinflammatory mediators and oxidative stress in cardiovascular complications.
      The specific targeting of these pathways may lead to novel therapies to reduce
      the burden of diabetic vascular complications.

PMID- 22390806
TI  - Potential cardiovascular effects of incretin-based therapies.
AB  - Glucagon-like peptide (GLP)-1 agonists and dipeptidyl peptidase-4 inhibitors are
      two classes of drugs that have been approved for treatment of Type 2 diabetes
      mellitus, based upon the glucose-lowering actions of the gastrointestinal hormone
      GLP-1. However, GLP-1 receptors are also present in cardiovascular tissues. Data
      from animal and in vitro studies suggest that GLP-1 may have cardioprotective
      effects and improve myocardial and endothelial dysfunction. Clinical data
      demonstrating cardiovascular effects are more limited, and there is some evidence
      that incretin-based therapies may be associated with improvements in
      cardiovascular risk factors. Large prospective cardiovascular outcome trials are
      underway to examine the cardiovascular safety of incretin-based therapies, and
      may reveal whether these agents are associated with any reduction in
      cardiovascular adverse events in patients with Type 2 diabetes mellitus.

PMID- 22390808
TI  - Statin use during pregnancy: a systematic review and meta-analysis.
AB  - Statins enjoy widespread acceptance as effective drugs to reduce morbidity and
      mortality in patients with and without cardiovascular disease, and are considered
      safe for long-term use. However, these compounds are contraindicated during
      pregnancy based on their potential teratogenic effects. Owing to the increasing
      number of young women eligible for statin therapy and the concern that the
      discontinuation of statin therapy might be harmful for both mother and child with
      hypercholesterolemia, gestational exposure to statins has increasingly become an
      issue of significant clinical importance. In this systematic review of both human
      and animal studies on the teratogenic effects of statins during pregnancy, we
      found that most of the available data in fact suggests that statins are unlikely
      to be teratogenic. In humans, the observed congenital anomalies were isolated and
      no consistent pattern has emerged to suggest that a common mechanism could
      underlie these observations. Animal studies show conflicting results, but in the
      reports in which an excess of congenital anomalies was reported in the statin
      treated rodents, excessive doses were used compared with the regimens we commonly
      prescribe to human subjects.

PMID- 22390807
TI  - HDL dysfunction in diabetes: causes and possible treatments.
AB  - HDL is known to be inversely correlated with cardiovascular disease due to its
      diverse antiatherogenic functions. These functions include cholesterol efflux and
      reverse cholesterol transport, antioxidative and anti-inflammatory activities.
      However, HDL has been shown to undergo a loss of function in several
      pathophysiological states, as in the acute phase response, obesity and chronic
      inflammatory diseases. Some of these diseases were also shown to be associated
      with increased risk for cardiovascular disease. One such disease that is
      associated with HDL dysfunction and accelerated atherosclerosis is diabetes
      mellitus, a disease in which the HDL particle undergoes diverse structural
      modifications that result in significant changes in its function. This review
      will summarize the changes that occur in HDL in diabetes mellitus and how these
      changes lead to HDL dysfunction. Possible treatments for HDL dysfunction are also
      briefly described.

PMID- 22390809
TI  - Guidelines for the prevention of cardiovascular disease in women: international
      challenges and opportunities.
AB  - Women are victims of cardiovascular disease (CVD) at rates similar to men. A
      reduction in CVD within developed nations has been noted and is primarily due to
      preventive efforts focused on risk factor modification. Middle- and low-income
      nations, however, have noted an increase in CVD. Efforts to reduce the occurrence
      of CVD risk factors targeting women's health in these populations are lacking and
      need to be encouraged. Risk factor modification with regards to hypertension,
      dyslipidemia, diabetes, tobacco use, abdominal obesity and psychosocial factors
      would provide the greatest reduction in CVD occurrence.

PMID- 22390810
TI  - Identification and management of orthostatic hypotension in older and medically
      complex patients.
AB  - Orthostatic hypotension is defined as a drop in systolic blood pressure (BP) of
      at least 20 mmHg or of diastolic BP of at least 10 mmHg within 3 min of standing.
      It is uncommon in the healthy elderly. However, it occurs in 30-50% of elderly
      persons with known risk factors and is another example of a multifactorial
      geriatric syndrome similar to falls and delirium. Most patients with orthostatic
      hypotension either have no symptoms or atypical symptoms, and therefore,
      screening BPs should be taken in all patients with risk factors. The treatment
      approach is not standardized but a stepped-care algorithm is presented that is
      likely to be successful for many patients. Future studies need to focus on the
      potential benefits of screening and treating patients with this disorder.

PMID- 22390812
TI  - Injectable solid peptide hydrogel as a cell carrier: effects of shear flow on
      hydrogels and cell payload.
AB  - beta-hairpin peptide-based hydrogels are a class of injectable solid hydrogels
      that can deliver encapsulated cells or molecular therapies to a target site via
      syringe or catheter injection as a carrier material. These physical hydrogels can
      shear-thin and consequently flow as a low-viscosity material under a sufficient
      shear stress but immediately recover back into a solid upon removal of the
      stress, allowing them to be injected as preformed gel solids. Hydrogel behavior
      during flow was studied in a cylindrical capillary geometry that mimicked the
      actual situation of injection through a syringe needle in order to quantify
      effects of shear-thin injection delivery on hydrogel flow behavior and
      encapsulated cell payloads. It was observed that all beta-hairpin peptide
      hydrogels investigated displayed a promising flow profile for injectable cell
      delivery: a central wide plug flow region where gel material and cell payloads
      experienced little or no shear rate, and a narrow shear zone close to the
      capillary wall where gel and cells were subject to shear deformation. The width
      of the plug flow region was found to be weakly dependent on hydrogel rigidity and
      flow rate. Live-dead assays were performed on encapsulated MG63 cells 3 h after
      injection flow and revealed that shear-thin delivery through the capillary had
      little impact on cell viability and the spatial distribution of encapsulated cell
      payloads. These observations help us to fundamentally understand how the gels
      flow during injection through a thin catheter and how they immediately restore
      mechanically and morphologically relative to preflow, static gels.

PMID- 22390814
TI  - S gene mutations of HBV in children with HBV-associated glomerulonephritis.
AB  - BACKGROUND: Hepatitis B virus-associated glomerulonephritis (HBV-GN) is a kind of
      immune complex-induced glomerulonephritis. The present study was designed to
      determine whether mutation of Hepatitis B virus (HBV) S gene is associated with
      glomerulonephritis in Chinese children. METHODS: Total 53 subjects, including 30
      HBV-GN, 5 nephrosis with HBV carriers (control group 1), and 18 HBV carriers
      (control group 2) were included in this study. Polymerase chain reaction (PCR)
      was used to detect the HBV-GN S gene mutation. RESULTS: (1) The serotype of HBV
      was adw in the majority (52/53) of subjects, and was adr in only 1 subject in the
      control group 2; (2) the genotype of HBV was the type B in 51 subjects, the type
      E in 1 HBV-GN child, and the type C in 1 HBV carrier; (3) Seventeen point
      mutations in the S gene of HBV were identified in 21 of 30 (70%) HBV-GN patients.
      Among them, 16 of 21 (76.2%) mutations may cause amino acid substitutions of the
      HBV proteins, which occur predominantly (11/16 mutations) at threonine, serine or
      tyrosine phosphorylation sites of mitogen-activated protein kinase (MAPK) or
      protein tyrosine kinase (PTK). (4) In addition, single nucleotide mutations
      without amino acid substitutions (same sense mutation) were found in 2 subjects
      in each control group and 5 subjects in HBV-GN group. CONCLUSIONS: HBV S gene
      mutations and the subsequent amino acid substitutions in HBV proteins were found
      in most children with HBV-GN, suggesting that these mutations may play an
      important role in the pathogenesis of HBV-GN.

PMID- 22390813
TI  - Brachial artery reactivity in patients with severe sepsis: an observational
      study.
AB  - INTRODUCTION: Ultrasound measurements of brachial artery reactivity in response
      to stagnant ischemia provide estimates of microvascular function and conduit
      artery endothelial function. We hypothesized that brachial artery reactivity
      would independently predict severe sepsis and severe sepsis mortality. METHODS:
      This was a combined case-control and prospective cohort study. We measured
      brachial artery reactivity in 95 severe sepsis patients admitted to the medical
      and surgical intensive care units of an academic medical center and in 52 control
      subjects without acute illness. Measurements were compared in severe sepsis
      patients versus control subjects and in severe sepsis survivors versus
      nonsurvivors. Multivariable analyses were also conducted. RESULTS: Hyperemic
      velocity (centimeters per cardiac cycle) and flow-mediated dilation (percentage)
      were significantly lower in severe sepsis patients versus control subjects
      (hyperemic velocity: severe sepsis = 34 (25 to 48) versus controls = 63 (52 to
      81), P < 0.001; flow-mediated dilation: severe sepsis = 2.65 (0.81 to 4.79)
      versus controls = 4.11 (3.06 to 6.78), P < 0.001; values expressed as median
      (interquartile range)). Hyperemic velocity, but not flow-mediated dilation, was
      significantly lower in hospital nonsurvivors versus survivors (hyperemic
      velocity: nonsurvivors = 25 (16 to 28) versus survivors = 39 (30 to 50), P <
      0.001; flow-mediated dilation: nonsurvivors = 1.90 (0.68 to 3.41) versus
      survivors = 2.96 (0.91 to 4.86), P = 0.12). Lower hyperemic velocity was
      independently associated with hospital mortality in multivariable analysis (odds
      ratio = 1.11 (95% confidence interval = 1.04 to 1.19) per 1 cm/cardiac cycle
      decrease in hyperemic velocity; P = 0.003). CONCLUSIONS: Brachial artery
      hyperemic blood velocity is a noninvasive index of microvascular function that
      independently predicts mortality in severe sepsis. In contrast, brachial artery
      flow-mediated dilation, reflecting conduit artery endothelial function, was not
      associated with mortality in our severe sepsis cohort. Brachial artery hyperemic
      velocity may be a useful measurement to identify patients who could benefit from
      novel therapies designed to reverse microvascular dysfunction in severe sepsis
      and to assess the physiologic efficacy of these treatments.

PMID- 22390815
TI  - Ultrasound-guided percutaneous tracheostomy in critically ill obese patients.
AB  - INTRODUCTION: The purpose of this study was to evaluate the feasibility of
      ultrasound (US)-guided percutaneous tracheostomy (PCT) and the incidence of
      complications in critically ill, obese patients. METHODS: Fifty consecutive
      patients were included in a prospective study in two surgical and critical care
      medicine departments. Obesity was defined as a body mass index (BMI) of at least
      30 kg/m2. The feasibility of PCT and the incidence of complications were compared
      in obese patients (n = 26) and non-obese patients (n = 24). Results are expressed
      as the median (25th-75th percentile) or number (percentage). RESULTS: The median
      BMIs were 34 kg/m2 (32-38) in the obese patient group and 25 kg/m2 (24-28) in the
      non-obese group (p < 0.001). The median times for tracheostomy were 10 min (8-14)
      in non-obese patients and 9 min (5-10) in obese-patients (p = 0.1). The overall
      complication rate was similar in obese and non-obese patient groups (35% vs. 33%,
      p = 0.92). Most complications were minor (hypotension, desaturation, tracheal
      cuff puncture and minor bleeding), with no differences between obese and non
      obese groups. Bronchoscopic inspection revealed two cases of granuloma (8%) in
      obese patients. One non-obese patient developed a peristomal skin infection,
      which was treated with intravenous antibiotics. Ultrasound-guided PCT was
      possible in all enrolled patients and there were no surgical conversions or
      deaths. CONCLUSIONS: This study demonstrated that US-guided PCT is feasible in
      obese patients with a low complication rate. Obesity may not constitute a contra
      indication for US-guided PCT. A US examination provides information on cervical
      anatomy and hence modifies and guides choice of the PCT puncture site. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01502657.

PMID- 22390817
TI  - Identifying the unknowns by aligning fragmentation trees.
AB  - Mass spectrometry allows sensitive, automated, and high-throughput analysis of
      small molecules. In principle, tandem mass spectrometry allows us to identify
      "unknown" small molecules not in any database, but the automated interpretation
      of such data is in its infancy. Fragmentation trees have recently been introduced
      for the automated analysis of the fragmentation patterns of small molecules. We
      present a method for the automated comparison of such fragmentation patterns,
      based on aligning the compounds' fragmentation trees. We cluster compounds based
      solely on their fragmentation patterns and show a good agreement with known
      compound classes. Fragmentation pattern similarities are strongly correlated with
      the chemical similarity of molecules. We present a tool for searching a database
      for compounds with fragmentation pattern similar to an unknown sample compound.
      We apply this tool to metabolites from Icelandic poppy. Our method allows fully
      automated computational identification of small molecules that cannot be found in
      any database.

PMID- 22390816
TI  - An analysis of lymphocyte phenotype after steroid avoidance with either
      alemtuzumab or basiliximab induction in renal transplantation.
AB  - Several studies have analyzed the phenotype of repopulated T-lymphocytes
      following alemtuzumab induction; however there has been less scrutiny of the
      reconstituted B-cell compartment. In the context of a randomized controlled trial
      (RCT) comparing alemtuzumab induction with tacrolimus monotherapy against
      basiliximab induction with tacrolimus and mycophenolate mofetil (MMF) therapy in
      renal transplantation, we analyzed the peripheral B- and T-lymphocyte phenotypes
      of patients at a mean of 25 +/- 2 months after transplantation. We examined the
      relationship between peripheral lymphocyte phenotype and graft function. Patients
      who received alemtuzumab had significantly higher numbers of B cells including
      naive, transitional and regulatory subsets. In contrast, the CD4(+)  T-cell
      compartment was dominated by a memory cell phenotype. Following either
      basiliximab or alemtuzumab induction patients with lower numbers of B cells or B
      subsets had significantly worse graft function. For alemtuzumab there was also a
      correlation between these subsets the stability of graft function and the
      presence of HLA-specific antibodies. These results demonstrate that a significant
      expansion of regulatory type B cells is associated with superior graft function
      and that this pattern is more common after alemtuzumab induction. This phenomenon
      requires further prospective study to see whether this phenotype could be used to
      customize immunotherapy.

PMID- 22390818
TI  - Prediction of arterial pressure increase after fluid challenge.
AB  - BACKGROUND: Mean arterial pressure above 65 mmHg is recommended for critically
      ill hypotensive patients whereas they do not benefit from supranormal cardiac
      output values. In this study we investigated if the increase of mean arterial
      pressure after volume expansion could be predicted by cardiovascular and renal
      variables. This is a relevant topic because unnecessary positive fluid balance
      increases mortality, organ dysfunction and Intensive Care Unit length of stay.
      METHODS: Thirty-six hypotensive patients (mean arterial pressure < 65 mmH)
      received a fluid challenge with hydroxyethyl starch. Patients were excluded if
      they had active bleeding and/or required changes in vasoactive agents infusion
      rate in the previous 30 minutes. Responders were defined by the increase of mean
      arterial pressure value to over 65 mmHg or by more than 20% with respect to the
      value recorded before fluid challenge. Measurements were performed before and at
      one hour after the end of fluid challenge. RESULTS: Twenty-two patients (61%)
      increased arterial pressure after volume expansion. Baseline heart rate, arterial
      pressure, central venous pressure, central venous saturation, central venous to
      arterial PCO2 difference, lactate, urinary output, fractional excretion of sodium
      and urinary sodium/potassium ratio were similar between responder and non
      responder. Only 7 out of 36 patients had valuable dynamic indices and then we
      excluded them from analysis. When the variables were tested as predictors of
      responders, they showed values of areas under the ROC curve ranging between 0.502
      and 0.604. Logistic regression did not reveal any association between variables
      and responder definition. CONCLUSIONS: Fluid challenge did not improve arterial
      pressure in about one third of hypotensive critically ill patients.
      Cardiovascular and renal variables did not enable us to predict the individual
      response to volume administration. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT00721604.

PMID- 22390819
TI  - Characterization and dating of blue ballpoint pen inks using principal component
      analysis of UV-Vis absorption spectra, IR spectroscopy, and HPTLC.
AB  - The ink of pens and ink extracted from lines on white photocopier paper of 10
      blue ballpoint pens were subjected to ultraviolet-visible (UV-Vis) spectroscopy,
      infrared (IR), and high-performance thin-layer liquid chromatography (HPTLC). The
      R(f)  values and color tones of the bands separated by thin-layer chromatography
      (TLC) analysis used to classify the writing inks into three groups. The principal
      component analysis (PCA) investigates the pen responsible for a piece of writing,
      and how time affects spectroscopy of written ink. PCA can differentiate between
      pen ink and ink line indicates the influence of solvent extraction process on the
      results. The PCA loadings are useful in individualization of a questioned ink
      from a database. The PCA of ink lines extracted at different times can be used to
      estimate the time at which a questioned document was written. The results proved
      that the UV-Vis spectra are effective tool to separate blue ballpoint pen ink in
      most cases rather than IR and HPTLC.

PMID- 22390820
TI  - The effects of sinus membrane pathology on bone augmentation and procedural
      outcome using minimal invasive antral membrane balloon elevation.
AB  - Abstract   Objectives: Membrane pathology tends to complicate the post procedural
      course of open sinus lift by ostio-meatal complex (OMC) obstruction and
      consequently acute sinusitis.  The objective of this study was to evaluate the
      outcome of subjects with considerable sinus membrane pathology undergoing
      maxillary sinus floor augmentation and simultaneously implants placement using
      the minimal invasive antral membrane balloon elevation (MIAMBE) method. Material
      and methods: Retrospective chart review of MIAMBE procedures performed in the
      presence of significant sinus membrane pathology. Results: 16 patients with
      maxillary sinus membrane thickening in well ventilated OMC as determined by
      dental computerized tomography (CT) underwent sinus augmentation and simultaneous
      implants placement using the MIAMBE technique. All 16 procedures were
      successfully concluded without significant procedural or post-procedural
      complications or implant failure. Post MIAMBE membrane pathology regressed or
      disappeared in 8 patients (50%) or remained unchanged in six 6 patients (37.5%),
      while in 2 patients the sinus membrane pathology was limited to evaluation by
      periapical x-rays. Conclusions: Sinus augmentation using the MIAMBE technique can
      be performed safely in asymptomatic patients in the presence of sinus membrane
      pathology if the OMC is not obstructed. In significant proportion of these cases
      complete resolution of the membrane pathology after MIAMBE is observed. When
      compared to open sinus lift, OMC obstruction is less likely to occur when
      employing the MIAMBE method.

PMID- 22390822
TI  - Cs3UGe7O18: a pentavalent uranium germanate containing four- and six-coordinate
      germanium.
AB  - A pentavalent uranium germanate, Cs(3)UGe(7)O(18), was synthesized under high
      temperature, high-pressure hydrothermal conditions at 585  degrees C and 160 MPa
      and structurally characterized by single-crystal X-ray diffraction and infrared
      spectroscopy. The valence state of uranium was confirmed by X-ray photoelectron
      spectroscopy and electron paramagnetic resonance. The room-temperature EPR
      spectrum can be simulated with two components using an axial model that are
      consistent with two distinct sites of uranium(V). In the structure of the title
      compound, each ([6])GeO(6) octahedron is bonded to six three-membered single-ring
      ([4])Ge(3)O(9)(6-) units to form germanate triple layers in the ab plane. Each
      layer contains nine-ring windows; however, these windows are blocked by adjacent
      layers. The triple layers are further connected by UO(6) octahedra to form a
      three-dimensional framework with intersecting six-ring channels along the <1 10>
      directions. The Cs(+) cation sites are fully occupied, ordered, and located in
      the cavities of the framework. Pentavalent uranium germanates or silicates are
      very rare, and only two uranium silicates and one germanate analogue have been
      published. However, all of them are iso-structural with those of the Nb or Ta
      analogues. In contrast, the title compound adopts a new structural type and
      contains both four- and six-coordinate germanium. Crystal data of
      Cs(3)UGe(7)O(18): trigonal, P3c1 (No. 165), a = 12.5582(4) A, c = 19.7870(6) A, V
      = 2702.50(15) A(3), Z = 6, D(calc) = 5.283 g.cm(-3), MU(Mo Kalpha) = 26.528 mm(
      1), R(1) = 0.0204, wR(2) = 0.0519 for 1958 reflections with I > 2sigma(I). GooF =
      1.040, rho(max,min) = 1.018, and -1.823 e.A(-3).

PMID- 22390821
TI  - Processing speed delays contribute to executive function deficits in individuals
      with agenesis of the corpus callosum.
AB  - Corpus callosum malformation and dysfunction are increasingly recognized causes
      of cognitive and behavioral disability. Individuals with agenesis of the corpus
      callosum (AgCC) offer unique insights regarding the cognitive skills that depend
      specifically upon callosal connectivity. We examined the impact of AgCC on
      cognitive inhibition, flexibility, and processing speed using the Color-Word
      Interference Test (CWIT) and Trail Making Test (TMT) from the Delis-Kaplan
      Executive Function System. We compared 36 individuals with AgCC and IQs within
      the normal range to 56 matched controls. The AgCC cohort was impaired on timed
      measures of inhibition and flexibility; however, group differences on CWIT
      Inhibition, CWIT Inhibition/Switching and TMT Number-Letter Switching appear to
      be largely explained by slow performance in basic operations such as color naming
      and letter sequencing. On CWIT Inhibition/Switching, the AgCC group was found to
      commit significantly more errors which suggests that slow performance is not
      secondary to a cautious strategy. Therefore, while individuals with agenesis of
      the corpus callosum show real deficits on tasks of executive function, this
      impairment appears to be primarily a consequence of slow cognitive processing.
      Additional studies are needed to investigate the impact of AgCC on other aspects
      of higher order cortical function.

PMID- 22390824
TI  - Primary actinomycosis of hand: A rare soft tissue infection.

PMID- 22390825
TI  - Individual budgets for people with incontinence: results from a 'shopping'
      experiment within the British National Health Service.
AB  - BACKGROUND AND CONTEXT: Most people with urinary incontinence are given limited
      choice when provided with absorbent products through the British National Health
      Service (NHS), even though the available range is large. OBJECTIVE: To
      investigate users' preferences for four disposable designs (inserts, all-in-ones,
      belted/T-shaped and pull-ups) and towelling washable/reusable products, day and
      night. DESIGN: Shopping experiment. SETTING AND PARTICIPANTS: Community-dwelling
      women and men in England with moderate-to-heavy urinary incontinence recruited to
      a larger trial. INTERVENTION: Participants tested each design and selected
      products they would prefer with a range of different budgets. MAIN OUTCOME
      MEASURES: Design preferences (rankings); 'purchasing' decisions from designated
      budgets. Results  Eighty-five participants (49 men) tested products, 75 completed
      the shopping experiment. Inserts, most frequently supplied by the NHS, were
      ranked second to pull-ups by women and lowest by men. When faced with budget
      constraints, up to 40% of participants opted to 'mix-and-match' designs. Over 15
      different combinations of products were selected by participants in the shopping
      experiment. Most (91%) stated a willingness to 'top-up' assigned budgets from
      income to secure preferred designs. DISCUSSION: Participants displayed diverse
      preferences. Enabling user choice of absorbent product design through individual
      budgets could improve satisfaction of consumers and efficiency of allocation of
      limited NHS resources. CONCLUSION: Recent policy for the NHS seeks to provide
      consumers with more control in their care. Extension of the concept of individual
      budgets to continence supplies could be feasible and beneficial for patients and
      provide better value-for-money within the NHS. Further research is warranted.

PMID- 22390826
TI  - Benzophenone synthase from Garcinia mangostana L. pericarps.
AB  - The cDNA of a benzophenone synthase (BPS), a type III polyketide synthase (PKS),
      was cloned and the recombinant protein expressed from the fruit pericarps of
      Garcinia mangostana L., which contains mainly prenylated xanthones. The obtained
      GmBPS showed an amino acid sequence identity of 77-78% with other plant BPSs
      belonging to the same family (Clusiaceae). The recombinant enzyme produced 2,4,6
      trihydroxybenzophenone as the predominant product with benzoyl CoA as substrate.
      It also accepted other substrates, such as other plant PKSs, and used 1-3
      molecules of malonyl CoA to form various phloroglucinol-type and polyketide
      lactone-type compounds. Thus, providing GmBPS with various substrates in vivo
      might redirect the xanthone biosynthetic pathway.

PMID- 22390828
TI  - Life at the extreme: lessons from the genome.
AB  - Extremophile plants thrive in places where most plant species cannot survive.
      Recent developments in high-throughput technologies and comparative genomics are
      shedding light on the evolutionary mechanisms leading to their adaptation.

PMID- 22390829
TI  - Reply to: Ahren B et al. Mechanisms of action of the dipeptidyl peptidase-4
      inhibitor vildagliptin in humans. Diabetes Obes Metab 2011; 13(9): 775-783 and
      Ahren B et al. Clinical evidence and mechanistic basis for vildagliptin's action
      when added to metformin. Diabetes Obes Metab 2011; 13(3): 193-203.

PMID- 22390827
TI  - Kinetics of Torpedo californica acetylcholinesterase inhibition by
      bisnorcymserine and crystal structure of the complex with its leaving group.
AB  - Natural and synthetic carbamates act as pseudo-irreversible inhibitors of AChE
      (acetylcholinesterase) as well as BChE (butyrylcholinesterase), two enzymes
      involved in neuronal function as well as in the development and progression of AD
      (Alzheimer's disease). The AChE mode of action is characterized by a rapid
      carbamoylation of the active-site Ser(200) with release of a leaving group
      followed by a slow regeneration of enzyme action due to subsequent
      decarbamoylation. The experimental AD therapeutic bisnorcymserine, a synthetic
      carbamate, shows an interesting activity and selectivity for BChE, and its
      clinical development is currently being pursued. We undertook detailed kinetic
      studies on the activity of the carbamate bisnorcymserine with Tc (Torpedo
      californica) AChE and, on the basis of the results, crystallized the complex
      between TcAChE and bisnorcymserine. The X-ray crystal structure showed only the
      leaving group, bisnoreseroline, trapped at the bottom of the aromatic enzyme
      gorge. Specifically, bisnoreseroline interacts in a non-covalent way with
      Ser(200) and His(440), disrupting the existing interactions within the catalytic
      triad, and it stacks with Trp(84) at the bottom of the gorge, giving rise to an
      unprecedented hydrogen-bonding contact. These interactions point to a dominant
      reversible inhibition mechanism attributable to the leaving group,
      bisnoreseroline, as revealed by kinetic analysis.

PMID- 22390830
TI  - Anxiety and negative self-schemas mediate the association between childhood
      maltreatment and paranoia.
AB  - This study examined affective and psychological routes from childhood
      maltreatment to increased paranoia in adulthood. Recent anxiety and negative
      beliefs about the self partially accounted for the associations between emotional
      or physical abuse and paranoia. However, as full mediation did not occur, other
      psychological, social and biological pathways require exploration.

PMID- 22390831
TI  - Cognitive activity, education and socioeconomic status as preventive factors for
      mild cognitive impairment and Alzheimer's disease.
AB  - Growing epidemiological evidence suggests that premorbid participation in
      cognitive leisure activities (CLA) reduces the risk of dementia by increasing
      cognitive reserve. We investigated the differential effect of CLA, education, and
      socioeconomic status (SES) on the development of mild cognitive impairment (MCI)
      and Alzheimer's disease (AD). Participants in the prospective population-based
      ILSE study (*1930-1932; 12-year follow-up) were examined in three examination
      waves (t1:1993/94; t2:1997/98; t3:2005/07). In total, 381 subjects of the
      original cohort (n=500) were re-examined at t3. Of these subjects 29% received
      the diagnosis of MCI and 7% of AD. Subjects participated in a thorough
      psychogeriatric examination and neuropsychological testing. Moreover, they took
      part in a detailed autobiographical interview and completed questionnaires
      including socio-demographic data and current frequency of participation in CLA.
      Subjects who were highly cognitively active at t1 had a significantly reduced
      risk of developing MCI/AD at t3 (scores adjusted for education, SES, gender, and
      depressive symptoms). Additionally, high education and high SES separately
      reduced the risk of MCI and AD. Our results confirm the hypothesis that a high
      level of CLA acts as a protective factor against the development of MCI and AD by
      increasing cognitive reserve. This effect is not accounted for by important
      potential confounders.

PMID- 22390832
TI  - Can a one-hour session of exposure treatment modulate startle response and reduce
      spider fears?
AB  - Preliminary evidence suggests that 3 hours of behavior therapy can reduce fear
      responses to phobic stimuli. Most of this research, however, has relied on self
      reports and clinician assessments, and failed to include a comparison group. To
      extend this literature, with 32 adults with spider phobia, we investigated the
      effects of a single hour of in vivo exposure on subjective and
      electrophysiological aspects of fear; comparisons were made to a wait-list
      control group. Pre- and post-assessments included phobia-relevant questionnaires
      and startle reflex responses to spider, negative, neutral and positive stimuli.
      Compared to the control group, our one-hour treatment reduced self-reported and
      physiological responses to spider stimuli. These data provide preliminary support
      for the ability of affective startle modulation to be changed by very brief
      exposure therapy.

PMID- 22390833
TI  - A search for obligatory paternal alleles in a DNA database to find an alleged
      rapist in a fatherless paternity case.
AB  - A sexual assault case resulted in a pregnancy, which was subsequently aborted.
      The alleged father of the fetus was unknown. Maternal and fetal types were
      obtained using the 11-locus AmpFlSTR((r))  SGM Plus((r))  kit. The national DNA
      database was searched for the paternal obligatory alleles and detected two
      suspects who could not be excluded as father of the male fetus. Additional typing
      using the AmpFlSTR((r))  Minifiler(TM)  kit, containing three additional
      autosomal loci, was not sufficient to exclude either suspect. Subsequent typing
      using the PowerPlex((r))  16, containing four additional loci, and Y-Filer(TM) 
      kits resulted in excluding one suspect. Searching a database for paternal
      obligatory alleles can be fruitful, but is fraught with possible false positive
      results so that finding a match must be taken as only preliminary evidence.

PMID- 22390834
TI  - Radical-regulating and antiviral properties of ascorbic acid and its derivatives.
AB  - The ability of ascorbic acid and a number of its derivatives to suppress
      replication of Herpes simplex virus type I was investigated in human
      rhabdomyosarcoma cell line. In parallel, interaction of the test compounds with
      carbon- and oxygen-centered radicals formed on radiolysis of hydroxyl-containing
      organic compounds was studied using the steady state radiolysis method. It has
      been shown that 2-O-glycoside of ascorbic acid, displaying marked antiviral
      properties against Herpes simplex virus type I, is also capable of inhibiting
      fragmentation and recombination reactions of alpha-hydroxyl-containing carbon
      centered radicals while not affecting processes involving oxygen-centered
      radicals.

PMID- 22390836
TI  - Overdispersion in marine fish parasites.
AB  - A modification of Taylor's Power law was used to compare the degree of
      overdispersion in frequency distributions from 38 datasets of marine parasites,
      data that had originally been collected for fish stock discrimination. The
      results strongly indicate that the overriding factor contributing to
      overdispersion in these helminths and crustaceans is the number of hosts in the
      life cycle. This was particularly well shown by juveniles of Anisakis 1 from
      different fish species. Data on the cestode Otobothrium cysticum and the
      monogenean Pricea multae appear anomalous and lead to conclusions about their
      biology not at first evident from the literature.

PMID- 22390835
TI  - Structure based design of iminohydantoin BACE1 inhibitors: identification of an
      orally available, centrally active BACE1 inhibitor.
AB  - From an initial lead 1, a structure-based design approach led to identification
      of a novel, high-affinity iminohydantoin BACE1 inhibitor that lowers CNS-derived
      Abeta following oral administration to rats. Herein we report SAR development in
      the S3 and F' subsites of BACE1 for this series, the synthetic approaches
      employed in this effort, and in vivo data for the optimized compound.

PMID- 22390837
TI  - A guide to Sonogashira cross-coupling reactions: the influence of substituents in
      aryl bromides, acetylenes, and phosphines.
AB  - The conversion-time data for 168 different Pd/Cu-catalyzed Sonogashira cross
      coupling reactions of five arylacetylenes (phenylacetylene; 1-ethynyl-2
      ethylbenzene; 1-ethynyl-2,4,6-R(3)-benzene (R = Me, Et, i-Pr)) and Me(3)SiCCH
      with seven aryl bromides (three 2-R-bromobenzenes (R = Me, Et, i-Pr); 2,6-Me(2)
      bromobenzene and three 2,4,6-R(3)-bromobenzenes (R = Me, Et, i-Pr)) with four
      different phosphines (P-t-Bu(3), t-Bu(2)PCy, t-BuPCy(2), PCy(3)) were determined
      using quantitative gas chromatography. The stereoelectronic properties of the
      substituents in the aryl bromides, acetylenes, and phosphines were correlated
      with the performance in Sonogashira reactions. It was found that the nature of
      the most active Pd/PR(3) complex for a Sonogashira transformation is primarily
      determined by the steric bulk of the acetylene; ideal catalysts are: Pd/P-t-Bu(3)
      or Pd/t-Bu(2)PCy for sterically undemanding phenylacetylene, Pd/t-BuPCy(2) for 2-
      and 2,6-substituted arylacetylenes or Me(3)SiCCH and Pd/PCy(3) for extremely
      bulky acetylenes and aryl bromides. Electron-rich and sterically demanding aryl
      bromides with substituents in the 2- or the 2,6-position require larger amounts
      of catalyst than 4-substituted aryl bromides. The synthesis of tolanes with bulky
      groups at one of the two aryl rings is best done by placing the steric bulk at
      the arylacetylene, which is also the best place for electron-withdrawing
      substituents.

PMID- 22390838
TI  - Arthroscopic findings in 32 joints affected by severe elbow incongruity with
      concomitant fragmented medial coronoid process.
AB  - OBJECTIVE: To report arthroscopic findings in dogs with severe elbow incongruity
      combined with fragmented medial coronoid process (FCP) and compare these findings
      in normal joints and congruent joints affected by FCP. STUDY DESIGN: Clinical
      study. ANIMALS: Dogs with elbow lameness (n = 40) and purpose bred dogs (5;
      controls). MATERIALS AND METHODS: Arthroscopic features of 32 severely
      incongruent joints with concomitant FCP were compared with 32 congruent elbow
      joints affected with FCP and 10 normal joints. A radioulnar step of >= 3 mm on
      radiographs and computed tomography (CT) scans was the selection criterion for a
      severely incongruent joint. Intraarticular structures were visually assessed at
      various sites within the joint. Regions of interest were: the radioulnar
      transition, humeroradial and humeroulnar joint space, trochlear notch, primary
      and secondary lesions of the medial coronoid process, and radial head. RESULTS:
      Incongruent joints had a radioulnar step and changes at the cartilage in the
      center of the trochlear notch, an irregular radioulnar transition, and an
      abnormal surface of the radial head. Coronoid pathology was present in every
      pathologic joint. CONCLUSION: Arthroscopy allowed detection of several features
      that were signs or consequences of severe elbow incongruity or accompanying
      inflammation. After a prominent radioulnar step, cartilage changes involving the
      radial head and trochlear notch were most frequently seen.

PMID- 22390839
TI  - Molecular characterization of a novel mycovirus in the cultivated mushroom,
      Lentinula edodes.
AB  - BACKGROUND: In the 1970s, mycoviruses were identified that infected the edible
      mushroom Lentinula edodes (shiitake), but they were not regarded as causal agents
      for mushroom diseases. None of their genes has been sequenced. In this study, the
      dsRNA genome of a mycovirus recently found in a shiitake commercial strain was
      sequenced and its molecular structure was characterized. METHODS: A cDNA library
      was constructed from a dsRNA purified from the fruiting body of L. edodes. The
      virus was tentatively named L. edodes mycovirus HKB (LeV). Based on the deduced
      RNA-dependent RNA polymerase (RdRp) sequence, phylogenetic analysis of LeV was
      conducted. Because no virion particles associated with the dsRNA were observed by
      electron microscopic observation, atomic force microscopy (AFM) observation was
      chosen for achieving molecular imaging of the virus. RESULTS: The 11,282-bp
      genome of LeV was obtained. The genome encoded two open reading frames (ORFs).
      ORF1 coded for a hypothetical protein and ORF2 for a putative RdRp, respectively.
      In addition, a region coding for a NUDIX domain was present in ORF1. There was a
      62-bp intergenic region between ORF1 and RdRp. Similarity with coat protein of
      mycoviruses was not found within the whole sequence. Based on phylogenetic
      analysis of the putative RdRp sequence, LeV grouped into a clade with dsRNA found
      in the basidiomycetes Phlebiopsis gigantea and Helicobasidium mompa. The clade
      was placed apart from the Totiviridae and Chrysoviridae families. As suggested
      from the genome sequence, AFM revealed that the structure of LeV was linear
      unencapsidated dsRNA. CONCLUSIONS: The results suggest that LeV represents a
      novel family of mycoviruses, found thus far only among the basidiomycetes.

PMID- 22390840
TI  - Very early recurrence of anti-Phospholipase A2 receptor-positive membranous
      nephropathy after transplantation.
AB  - Membranous nephropathy is a common cause of adult nephrotic syndrome, with recent
      evidence suggesting that 70% of idiopathic disease is associated with anti
      Phospholipase A(2)  receptor autoantibodies. We describe a 63-year-old man with
      membranous nephropathy who underwent a kidney transplant and developed recurrent
      membranous nephropathy with fine granular co-localization of Phospholipase A(2) 
      receptor and IgG evident on transplant biopsy on day 6 and elevated circulating
      levels of serum anti-Phospholipase A(2)  receptor autoantibody that declined over
      time in conjunction with improvement in the serum creatinine and urinary protein.
      This is a very early case of Phospholipase A(2)  receptor-associated recurrent
      membranous nephropathy with circulating anti-Phospholipase A(2)  receptor
      autoantibody, which supports the emerging evidence that idiopathic membranous
      nephropathy is an autoimmune disease.

PMID- 22390841
TI  - Deficient post-error slowing in children with ADHD is limited to the inattentive
      subtype.
AB  - Post-error slowing (i.e., slowing of a response on correct trials following an
      error) is thought to reflect adaptive behavior that may be impaired in Attention
      Deficit/Hyperactivity Disorder (ADHD). The current study examined post-error
      slowing in children with ADHD and typically developing controls on two cognitive
      tasks. Fifty-one ADHD-Combined type, 53 ADHD-Inattentive type, and 47 controls
      completed a Choice Discrimination and Stop Signal Task with incentive and event
      rate manipulations. Linear mixed models were used to examine reaction times
      surrounding errors (trial-by-trial). Pre-error speeding and pre- to post-error
      slowing occurred on both tasks. Impaired post-error slowing was only present on
      the Choice Discrimination Task for the ADHD-Inattentive type. Post-error slowing
      is impaired in children with ADHD-Inattentive type, but not ADHD-Combined type,
      on a simple attention task. These findings highlight the importance of
      considering task demands and ADHD subtype when examining post-error slowing and
      also provide a novel approach to quantifying post-error slowing.

PMID- 22390842
TI  - ECC-RT-PCR: a new method to determine the viability and infectivity of Giardia
      cysts.
AB  - BACKGROUND: Giardia sp is a major cause of diarrheal illness worldwide, and
      millions of people are infected each year. Rapid methods to determine the
      infectivity and virulence of isolates are critical for the development of
      intervention strategies to control the transmission of Giardia sp cysts, which
      occurs through contaminated surfaces, food, and water. However, determining the
      viability, infectivity, and virulence of Giardia sp cysts using molecular methods
      is a technical challenge because of the lack of a cell culture model. METHOD:
      This study was designed to evaluate mRNA expression in trophozoites and to assess
      trophozoite attachment to cell monolayer and changes in transcellular resistance
      as an indicator of Giardia sp viability and infectivity. Heat shock mRNA in
      Giardia cysts and variant-specific protein (VSP) mRNA in trophozoites were
      quantified by reverse transcription polymerase chain reaction (RT-PCR). C2bb
      (Caco-2) cells were grown on transwell chambers to study the attachment of
      trophozoites, changes in transcellular resistance, and expression of VSP in
      trophozoites. RESULTS: The results of these molecular and cell culture studies
      indicate a direct linear correlation between the viability and infectivity of
      fresh stocks of Giardia sp cysts. The attachment of trophozoites to cell
      monolayer, expression of VSP, and change in the transcellular resistance was
      directly correlated with their infectivity in neonatal mice. PCR was successfully
      combined with the electrophysiological analysis of cell culture (ECC-RT-PCR) post
      trophozoite attachment. CONCLUSION: This study shows that the ECC-RT-PCR, a new
      integrated cell culture assay, can be used as a rapid and cost-effective tool for
      assessing the viability and infectivity of environmental isolates of Giardia sp
      cysts.

PMID- 22390843
TI  - High frequency of Helicobacter pylori in the esophageal mucosa of dyspeptic
      patients and its possible association with histopathological alterations.
AB  - BACKGROUND: Helicobacter pylori gastric colonization is known to be high in
      symptomatic subjects. However, only a few reports on the presence of H. pylori in
      the esophageal mucosa have been published. The aim of this study was to assess
      the frequency of H. pylori in the esophagus of dyspeptic patients and its
      association with histopathology. METHODS: The presence of H. pylori in the
      gastroesophageal mucosa was detected by fluorescence in situ hybridization (FISH)
      and PCR analysis of DNA extracted from gastric and esophageal biopsies of 82
      symptomatic patients, using genus- and species-specific PCR primers. Alterations
      in the gastroesophageal mucosa were assessed by conventional histological
      techniques. RESULTS: H. pylori in the stomach was detected by PCR and FISH,
      respectively, in 61% (n=43) and 90% (n=63) of dyspeptic patients, and in the
      esophagus in 70% (n=44) and 73% (n=46). The prevalence of cagA-positive strains
      by PCR varied from 50% (n=35) in the gastric mucosa to 65% (n=41) in the
      esophageal mucosa. By combining the results of both methods, H. pylori was
      present in the gastroesophageal mucosa in 86% (n=68) of patients. The association
      of the presence of bacteria, including H. pylori, in the esophageal mucosa with
      histopathological alterations was statistically significant between
      microabscesses and bacteria (r=0.656, p<0.0001) and PCR detection and
      pseudogoblet cells (r=0.25, p<0.047). CONCLUSIONS: This is the first report of
      the occurrence of H. pylori in the esophageal mucosa from dyspeptic Venezuelan
      patients. These results demonstrate the high prevalence of H. pylori in the
      esophagus, and its presence was correlated with signs of inflammation.

PMID- 22390844
TI  - High frequency variations of Helicobacter pylori isolates in individual hosts in
      a Chinese population.
AB  - BACKGROUND: Colonization of individual hosts by multiple Helicobacter pylori
      genotypes may be one reason why this infection is persistent and difficult to
      eradicate. METHODS: In order to study the diversity of H. pylori in individuals,
      a modified randomly amplified polymorphic DNA (RAPD) method was applied using
      primary culture isolates instead of passaged cultures. RESULTS: The results
      showed that variations in H. pylori were prevalent among individuals in the
      Chinese population, and the incidence of multiple colonization was 99.1%
      (115/116), significantly higher than in other reports. Moreover, the number of
      RAPD genotypes was found to be significantly associated with the process of
      disease development (p<0.05). Indeed, a trend for a higher number of RAPD
      genotypes within a single host (up to five genotypes) was observed as the disease
      developed or became more serious. After subculturing for three generations in our
      experiment, some genotypes present in the primary cultures were lost. The
      different genotypes in one patient may have originated from a single ancestral
      strain, as determined by analysis of six H. pylori housekeeping gene alleles,
      most of which were shown to be identical. CONCLUSIONS: These results suggest that
      investigating isolates of the primary culture will better reflect the H. pylori
      diversity in individuals. Also, they indicate that continuous variation of one
      strain in the gastric microenvironment may be the main cause of H. pylori
      diversity in individuals in the Chinese population.

PMID- 22390845
TI  - Effect of narrow-band ultraviolet B phototherapy on production of antinuclear
      antibodies.

PMID- 22390846
TI  - Glycopolymer modification on physicochemical and biological properties of poly(L
      lysine) for gene delivery.
AB  - Poly(L-lysine) (PLL) has excellent plasmid DNA (pDNA) condensation capacity.
      However, the relatively high cytotoxicity and low transfection efficiency limit
      its application as gene delivery vectors. Here, well-defined glycopolymers are
      synthesized by reversible addition fragmentation transfer polymerization and
      grafted onto PLL to improve the gene delivery performance. After glycopolymer
      modification, PLL shows reduced cytotoxicity. By regulating the glycopolymer
      length and amino group substitution degree, the glycopolymer modified PLL can
      condense pDNA with proper strength, protect the condensed pDNA from degradation
      and release them in time. Transfection with NIH3T3 and HepG2 cells shows that the
      glycopolymer modified PLL has improved transfection efficiencies. The low
      cytotoxicity, effective pDNA protection and enhanced transfection efficiencies
      indicate that glycopolymer modification would be an effective strategy to improve
      the polycation properties for gene delivery.

PMID- 22390847
TI  - Synthesis, drug release and anti-HIV activity of a series of PEGylated zidovudine
      conjugates.
AB  - A series of methoxy poly(ethylene glycol)-succinyl-5'-O-zidovudine conjugates
      (mPEG-succinyl-AZT) with different molecular weight (M(w): 750 Da, 2, 5 or 10
      kDa) of mPEG were synthesized and characterized by Fourier transform infrared
      (FTIR) spectroscopy, (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy, and
      matrix-assisted laser desorption/ionization time of flight mass (MALDI TOF MS)
      spectrometry analysis. All conjugates showed good stability in vitro release
      experiments, and good anti-HIV activity and low cytotoxicity in MT-4 cells, in
      which, mPEG(750)-succinyl-AZT exhibited good inhibition to wild-type viruses
      (strains IIIB and ROD) with EC(50) values of 0.11 and 0.090 MUmol/L,
      respectively, and it showed no cytotoxicity up to 110 MUmol/L. Oral
      pharmacokinetic study in rats showed the half-life time (T(1/2)) of all
      conjugates are prolonged compared to free AZT. Especially, mPEG(750)-succinyl-AZT
      displayed a ~2.3-fold prolonged half-life and approximately 224% increased
      bioavailability of AZT.

PMID- 22390848
TI  - Self-assembly of beta-lactoglobulin and the soluble fraction of gum tragacanth in
      aqueous medium.
AB  - Spectrophotometric and light scattering measurements, along with optical
      microscopy, were used to follow the complexation and coacervation process that
      occur when beta-lactoglobulin (BLG)/tragacanthin (T) mixed dispersions (0.3 wt.%
      total concentration; BLG:T ratio of 2:1) were brought from pH 6 to pH 2. In
      addition, the coupling of slow in situ acidification of the mixture and rheometry
      was utilised to gain deeper insights into pH-induced structural transitions
      during the assembly process. The results obtained by this multi-methodological
      approach allowed the associative phase separation process to be parameterised in
      terms of a set of characteristic pH values (~5.3, ~4.8, ~4.5, ~4.15, ~4, ~3.8,
      ~2.5) at which critical structural changes took place. Investigation of the
      absorbance profiles of complexed/coacervated systems as a function of time
      revealed that several transitions could occur at different time scales.
      Morphological changes in the assemblies and the subsequent formation of some
      flocculant substances during the late stage of process were clearly visualised
      using microscopy.

PMID- 22390849
TI  - Preparation, characterization and evaluation of biocomposite films containing
      chitosan and sago starch impregnated with silver nanoparticles.
AB  - The positive attributes of excellent biocompatibility and biodegradability of
      biopolymers with versatile biological activities have provided ample
      opportunities for further development of functional biomaterials of high
      potential in various fields. The biopolymers used in this study, i.e. chitosan
      and sago starch are abundantly available in nature and can be used in various
      biomedical applications. In the present study, the composite films of chitosan
      (Ch) and sago starch (SG) impregnated with silver nanoparticles (AgNP) with and
      without antibiotic gentamicin (G) were prepared by solvent casting method. The
      films prepared were characterized for their physic-chemical properties using
      conventional methods. The results obtained showed that with the increase of
      chitosan content in the composite results in decrease in its water absorption
      capacity. The FTIR and SEM studies have shown the composite nature of the films
      prepared. Ch-SG-AgNP and Ch-SG-AgNP-G composites were used as wound dressing
      materials in experimental wounds of rats. The healing pattern of the wounds was
      evaluated by planimetric studies, macroscopic observations, biochemical studies
      and histopathological observations. The results have shown faster healing pattern
      in the wounds treated with Ch-SG-AgNP and Ch-SG-AgNP-G composites compared to
      untreated control. This study suggests that Ch-SG-AgNP film may be a potential
      candidate as a dressing material for wound healing applications.

PMID- 22390850
TI  - Nano photo scouring and nano photo bleaching of raw cellulosic fabric using nano
      TiO2.
AB  - Photo catalytic action of nano TiO(2) for decomposing of some organic compounds
      is a well known phenomenon. This can be extended to the application on nano
      TiO(2) on the desized cotton fabric to decompose the hydrophobic impurities and
      coloring matters of the fabric. This can be nominating as a replacement for the
      conventional scouring and bleaching processes on cotton fabric producing the
      hydrophilic white cotton fabric. The photo activities of the nano TiO(2) on the
      desized cotton through decomposition of the cotton impurities compared for two
      different light exposures: UV rays and daylight. The desized cotton fabrics
      treated in the ultrasonic bath containing a colloidal aqueous solution of nano
      TiO(2)/citric acid (CA)/sodium hypophosphite (SHP). Incorporating CA in the
      treatment bath enhanced the treatment durability against washing, created a
      durable hydrophilic white cotton fabric even after several successive washings.
      Increasing the nano TiO(2) content enhanced the fabric hydrophilicity and
      whiteness features. Overall, the nano photo scouring and nano photo bleaching on
      the cotton fabric introduced and thoroughly discussed. This gains the application
      of nano TiO(2) on textile materials besides the other well known characteristics
      obtained on the textiles including self-cleaning, antibacterial and UV
      protection.

PMID- 22390851
TI  - A polysaccharide from Agaricus blazei inhibits proliferation and promotes
      apoptosis of osteosarcoma cells.
AB  - Many reports have proved that traditional Chinese herbal medicines (TCM) have
      become popular used in disease prevention and as alternatives to cancer
      chemotherapy. In this study, we purified a polysaccharide (ABP-Ia) from the
      fruiting bodies of Agaricus blazei and identified its molecular weight to be
      4.2*10(5)Da. ABP-Ia was a heteropolysaccharide fraction consisting of glucose,
      mannose, and galactose in a molar ratio of 1:1:1, along with trace of rhamnose.
      The effect of ABP-Ia at three concentrations of 100, 200 and 400 MUg/mL on the
      cell growth and apoptosis was evaluated in osteosarcoma cell lines HOS and a
      normal human osteoblast cell line NHOst. ABP-Ia had a significant inhibitory
      effect against the growth of HOS cells, whereas a mild cytotoxicity to the HOS
      cells mediated by ABP-Ia was observed, which was in accordance with the results
      that ABP-Ia substantially induced apoptosis in a dose-dependent fashion in the
      HOS cells. However ABP-Ia had no or minor inhibitory and cytotoxic effects on the
      viability of NHOst cells even at the high concentration of 400 MUg/mL. Base on
      all the observations, we could conclude that ABP-Ia had an evident inhibitory
      effect on the growth of HOS cells mainly through induction of apoptosis, with a
      minor toxicity to normal human osteoblast cell.

PMID- 22390852
TI  - Automating a combined composite-consensus method to generate DNA profiles from
      low and high template mixture samples.
AB  - We present an automated method to generate DNA profiles from replicate PCRs by
      combining advantages of the composite and consensus method by a system of
      brackets in which an allelic balance threshold is used as a variable to separate
      DNA-profiles of major from minor donors. Through the analysis of artificial low
      (125 pg) and high (250 pg) template three-person mixtures with low (1:1.5:3) and
      high (1:5:10) donor ratios we demonstrate the usefulness of a tool to determine
      the optimal allelic balance threshold within a locus. The automated extraction of
      dominant profiles saves considerable amounts of time when producing composite
      consensus profiles. Drop-in/drop-out rates are produced and a comparison is made
      with an alternative open source script to evaluate the dominant profiles
      generated. By introducing this script into the forensic community we hope to
      increase awareness of much needed collaborative efforts with bioinformaticians
      and statisticians to develop forensic open source software scripts.

PMID- 22390853
TI  - FamLink--a user friendly software for linkage calculations in family genetics.
AB  - The present number of STR loci adopted in relationship testing is chiefly limited
      to unlinked markers, in most cases residing on different chromosomes. In order to
      solve more complex cases of relatedness, e.g. deficient paternities and disputed
      sibships, the number of core loci can be extended. The inclusion of multiple loci
      on the same chromosome will, however, increase the risk of possible linkage
      between markers. We present a new software, FamLink, freely available from
      http://www.FamLink.se, that can perform statistical calculations based on
      pedigree structures and account for linkage between pairs of markers. In
      addition, FamLink can simulate genotype data in order to study the effect of
      accounting for linkage or not. We demonstrate the importance of taking linkage
      properly into account using examples and real cases.

PMID- 22390854
TI  - Testing the utility of a cancer clinical trial specific Question Prompt List (QPL
      CT) during oncology consultations.
AB  - OBJECTIVE: A Question Prompt List (QPL) is a proven, simple intervention to aid
      patients to be active participants in consultations with their physicians by
      asking questions. We aimed to further develop and test the efficacy of a targeted
      QPL for clinical trials (QPL-CT). METHODS: Breast, Lung and Genitourinary cancer
      patients who were facing a discussion about a therapeutic clinical trial
      completed short pre- and post-consultation questionnaires and used the QPL-CT in
      their discussions with their oncologists. RESULTS: 30 participants were recruited
      from 6 oncologists. All QPL-CT questions were selected by at least one-third of
      participants. Participants mostly wanted and asked questions about personal trial
      benefit. Oncologists provided information about personal benefit to varying
      degrees, thus patients did not ask some questions. Patients were still left with
      some unasked and unanswered questions. CONCLUSION: The QPL-CT has potential as a
      simple, inexpensive intervention to aid such communication. Further investigation
      is needed to demonstrate the efficacy of the QPL-CT in improving cancer patient
      outcomes. PRACTICE IMPLICATIONS: These preliminary finding suggest that important
      areas of clinical trials are overlooked in clinical consultations. The QPL-CT may
      be an effective method to encourage oncologists to endorse patient question
      asking about clinical trials and prompt patient questions.

PMID- 22390855
TI  - Temporal dynamics of Arc gene induction in hippocampus: relationship to context
      memory formation.
AB  - Past studies have proposed a role for the hippocampus in the rapid encoding of
      context memories. Despite this, there is little data regarding the molecular
      processes underlying the stable formation of a context representation that occurs
      in the time window established through such behavioral studies. One task that is
      useful for investigating the rapid encoding of context is contextual fear
      conditioning (CFC). Behavioral studies demonstrate that animals require
      approximately 30 s of exploration prior to a footshock to form a contextual
      representation supporting CFC. Thus, any potential molecular process required for
      the stabilization of the cellular representation for context must be activated
      within this narrow and behaviorally defined time window. Detection of the
      immediate-early gene Arc presents an ideal method to assess the activation of
      specific neuronal ensembles, given past studies showing the context specific
      expression of Arc in CA3 and CA1 subfields and the role of Arc in hippocampal
      long-term synaptic plasticity. Therefore, we examined the temporal dynamics of
      Arc induction within the hippocampus after brief context exposure to determine
      whether experience-dependent Arc expression could be involved in the rapid
      encoding of incidental context memories. We found that the duration of context
      exposure differentially activated Arc expression in hippocampal subfields, with
      CA3 showing rapid engagement within as little as 3 s of exposure. By contrast,
      Arc induction in CA1 required 30 s of context exposure to reach maximal levels. A
      parallel behavioral experiment revealed that 30 s, but not 3 s, exposure to a
      context resulted in strong conditioned freezing 24 h later, consistent with past
      studies from other laboratories. The current study is the first to examine the
      rapid temporal dynamics of Arc induction in hippocampus in a well-defined context
      memory paradigm. These studies demonstrate within 30 s of context exposure Arc is
      fully activated in CA3 and CA1, suggesting that the engagement of plastic
      processes requiring Arc function (such as long-term potentiation) occurs within
      the same temporal domain as that required for behavioral conditioning.

PMID- 22390856
TI  - Selective lesions of the dentate gyrus produce disruptions in place learning for
      adjacent spatial locations.
AB  - The hippocampus (HPP) plays a known role in learning novel spatial information.
      More specifically, the dentate gyrus (DG) hippocampal subregion is thought to
      support pattern separation, a mechanism for encoding and separating spatially
      similar events into distinct representations. Several studies have shown that
      lesions of the dorsal DG (dDG) in rodents result in inefficient spatial pattern
      separation for working memory; however, it is unclear whether selective dDG
      lesions disrupt spatial pattern separation for reference memory. Therefore, the
      current study investigated the role of the dDG in pattern separation using a
      spatial reference memory paradigm to determine whether the dDG is necessary for
      acquiring spatial discriminations for adjacent locations. Male Long-Evans rats
      were randomly assigned to receive bilateral intracranial infusions of colchicine
      or saline (control) into the dDG. Following recovery from surgery, each rat was
      pseudo-randomly assigned to an adjacent arm or separate arm condition and
      subsequently tested on a place-learning task using an eight-arm radial maze. Rats
      were trained to discriminate between a rewarded arm and a nonrewarded arm that
      were either adjacent to one another or separated by a distance of two arm
      positions. Each rat received 10 trials per day and was tested until the animal
      reached a criterion of nine correct choices out of 10 consecutive trials across 2
      consecutive days of testing. Both groups acquired spatial discriminations for the
      separate condition at similar rates. However, in the adjacent condition, dDG
      lesioned animals required significantly more trials to reach the learning
      criterion than controls. The results suggest that dDG lesions decrease efficiency
      in pattern separation resulting in impairments in the adjacent condition
      involving greater overlap among the distal cues. Conversely, in the separate
      condition, there was less overlap among distal cues during encoding and less need
      for pattern separation. These findings provide further support for a critical
      role for the dDG in spatial pattern separation by demonstrating the importance of
      a processing mechanism that is capable of reducing interference among overlapping
      spatial inputs across a variety of memory demands.

PMID- 22390857
TI  - Roles of dopamine D1 and D2 receptors in the acquisition and expression of fat
      conditioned flavor preferences in rats.
AB  - Sugars and fats elicit innate and learned flavor preferences with the latter
      mediated by flavor-flavor (orosensory) and flavor-nutrient (post-ingestive)
      processes. Systemic dopamine (DA) D1 (SCH23390: SCH) and D2 (raclopride: RAC),
      but not opioid antagonists blocked the acquisition and expression of flavor
      flavor preferences conditioned by sugars. In addition, systemic D1, but not D2 or
      opioid antagonists blocked the acquisition of flavor-nutrient preferences
      conditioned by intragastric (IG) sugar infusions. Given that DA antagonists
      reduce fat intake, the present study examined whether systemic D1 or D2
      antagonists altered the acquisition and/or expression of conditioned flavor
      preferences (CFP) produced by pairing one novel flavor (CS+, e.g., cherry) with a
      3.5% corn oil (CO: fat) solution relative to another flavor (CS-, e.g., grape)
      paired with a 0.9% CO solution. In an expression study, food-restricted rats were
      trained to drink either flavored 3.5% or 0.9% CO solutions on alternate days.
      Subsequent two-bottle tests with the CS+ and CS- flavors mixed in 0.9% CO
      solutions occurred 0.5h after systemic administration of vehicle (VEH), SCH (50
      800 nmol/kg) or RAC (50-800 nmol/kg). The rats displayed a robust CS+ preference
      following VEH treatment (87-88%) the expression of which was attenuated by
      treatment with moderate doses of RAC, and to a lesser degree, SCH. In an
      acquisition study, six groups of rats received VEH, SCH (25, 50, 200 nmol/kg) or
      RAC (50, 200 nmol/kg) 0.5 h prior to 1-bottle training trials with CS+ flavored
      3.5% and CS- flavored 0.9% (CS-) CO solutions. A seventh Limited VEH group was
      trained with its training intakes limited to that of the SCH and RAC groups.
      Subsequent two-bottle tests were conducted with the CS+ and CS- flavors presented
      in 0.9% CO without injections. Significant and persistent CS+ preferences were
      observed in VEH (75-82%), Limited VEH (70-88%), SCH25 (75-84%), SCH50 (64-87%),
      SCH200 (78-91%) and RAC200 (74-91%) groups. In contrast, the group trained with
      RAC50 displayed a significant initial CS+ preference (76%) which declined over
      testing to 61%. These data indicate limited DA D1 and D2 receptor signaling
      involvement in the expression and acquisition of a fat-CFP relative to previous
      robust effects for sugar-CFP.

PMID- 22390858
TI  - Opioid mechanisms are involved in the disruption of arcaine-induced amnesia by
      context pre-exposure.
AB  - Previous exposure to the training context disrupts glutamatergic N-methyl-d
      aspartate receptor (NMDAr) antagonist-induced amnesia, indicating that novelty is
      necessary for such an amnestic effect. While there are reports that novelty
      related release of opioids cause amnesia, no study has addressed whether the
      amnestic effect of NMDAr antagonists involve opioid mechanisms. In this study we
      investigated whether pharmacological manipulation of the opioid system
      immediately after context pre-exposure alters the amnestic effect of arcaine, a
      NMDAr antagonist. Adult male Wistar rats were habituated (pre-exposed) to a fear
      conditioning training apparatus or to a different context (open field).
      Immediately after pre-exposure, animals were injected with saline or naloxone
      (0.5 mg/kg, i.p.) or anti-beta-endorphin antibody (1:500, i.c.v.). Forty eight
      hours after pre-exposure session, all animals were subjected to fear conditioning
      acquisition protocol and saline or arcaine (30 mg/kg, i.p.) was administered
      immediately after training. Testing was carried out 24 h later, and freezing
      responses due to re-exposure to the training apparatus were recorded. Pre
      exposure to the training apparatus prevented the impairment of memory induced by
      post-training arcaine. Administration of naloxone or anti-beta-endorphin
      antibody, immediately after pre-exposure to the training apparatus, reinstated
      the amnesic effect of post-training arcaine. The results suggest that endogenous
      opioid mechanisms are involved in the pre-exposure-induced loss of the amnestic
      effect of arcaine.

PMID- 22390859
TI  - Hippocampal metabolites and memory performances in patients with amnestic mild
      cognitive impairment and Alzheimer's disease.
AB  - In patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's
      disease (AD), previous studies have reported the decrease of N-acetylaspartate
      (NAA) concentration and the increase of myo-inositol (MI) concentration using
      proton magnetic resonance spectroscopy (1H-MRS). However, it remains to be
      investigated what aspects of cognition these metabolite changes reflect. In this
      study we evaluated the correlations between the subtests of Wechsler Memory Scale
      Revised (WMS-R) and the concentrations of NAA and MI. The study group was
      composed of 42 patients with aMCI and 67 patients with AD. 1H-MR spectra with a
      single voxel-point resolved spectroscopy (PRESS) at a short echo time were
      acquired from the bilateral hippocampi and posterior cingulate gyrus. Positive
      correlations were shown between the NAA concentration in the left hippocampus and
      verbal memory, visual memory, general memory, attention and delayed recall; and
      furthermore, between the NAA concentration in the right hippocampus and verbal
      memory and general memory. Negative correlations were shown between the MI
      concentration in the left hippocampus and verbal memory, general memory, and
      delayed recall, and between the MI concentration in the right hippocampus and
      verbal memory. There was no significant correlation between any subtest of WMS-R
      and these two metabolite concentrations in the posterior cingulate gyrus. These
      findings suggest that bilateral, especially left hippocampal NAA and MI
      concentrations are associated with memory dysfunction observed in patients with
      aMCI and AD. In contrast, NAA and MI concentrations in the posterior cingulate
      gyrus may be less related to memory function than those in the hippocampus.

PMID- 22390860
TI  - Tackling creativity at its roots: evidence for different patterns of EEG alpha
      activity related to convergent and divergent modes of task processing.
AB  - The distinction between convergent and divergent cognitive processes given by
      Guilford (1956) had a strong influence on the empirical research on creative
      thinking. Neuroscientific studies typically find higher event-related
      synchronization in the EEG alpha rhythm for individuals engaged in creative
      ideation tasks compared to intelligence-related tasks. This study examined,
      whether these neurophysiological effects can also be found when both cognitive
      processing modes (convergent vs. divergent) are assessed by means of the same
      task employing a simple variation of instruction. A sample of 55 participants
      performed the alternate uses task as well as a more basic word association task
      while EEG was recorded. On a trial-by-trial basis, participants were either
      instructed to find a most common solution (convergent condition) or a most
      uncommon solution (divergent condition). The answers given in the divergent
      condition were in both tasks significantly more original than those in the
      convergent condition. Moreover, divergent processing was found to involve higher
      task-related EEG alpha power than convergent processing in both the alternate
      uses task and the word association task. EEG alpha synchronization can hence
      explicitly be associated with divergent cognitive processing rather than with
      general task characteristics of creative ideation tasks. Further results point to
      a differential involvement of frontal and parietal cortical areas by individuals
      of lower versus higher trait creativity.

PMID- 22390861
TI  - High on-treatment platelet reactivity by ADP and increased risk of MACE in good
      clopidogrel metabolizers.
AB  - High on-treatment platelet reactivity (HPR) by ADP, which primarily reflects the
      effect of thienopyridines, has been found to be an independent predictor of
      ischemic events in patients with acute coronary syndrome (ACS) on dual
      antiplatelet therapy. CYP2C19*2 is associated with HPR by ADP. The aim of our
      study was to evaluate if high on-clopidogrel platelet reactivity (HPR) by ADP is
      associated with an increased risk of major adverse coronary events (MACE) after
      ACS independent of CYP2C19*2 allele, i.e. whether genotyping patients for
      CYP2C19*2 polymorphism is sufficient to identify those to be switched to novel
      antiplatelets. A total of 1187 patients were included (CYP2C19 *1/*1 n = 892;
      *1/*2 n = 264; *2/*2 n = 31); 76 MACE (CV death and non-fatal MI) were recorded
      in non-carriers of CYP2C19*2 (8.5%) and 39 in carriers of CYP2C19*2 (13.2%). At
      the landmark analysis in the first 6 months, HPR by ADP and CYP2C19*2 allele were
      both significantly and independently associated with MACE [HPR by ADP: HR = 2.0
      (95% CI 1.2-3.4), p = 0.01; CYP2C19*2 allele: HR = 2.3 (95% CI 1.3-3.9), p =
      0.003]. At the land mark analysis from 7 to 12 months, only HPR by ADP remained
      significantly associated with the risk of MACE [HPR by ADP: HR = 2.7 (95% CI 1.4
      5.3), p = 0.003; CYP2C19*2: HR = 0.8 (95% CI 0.2-1.1), p = ns]. CYP2C19*2 allele
      and HPR by ADP are both independently associated with an increased risk of MACE
      in the first 6 months after ACS. HPR by ADP is associated with an increased risk
      until 12 months of follow-up. Therefore, both phenotype and genotype are
      clinically relevant for the evaluation of the antiplatelet effect of clopidogrel
      and for the prognostic stratification of ACS patients.

PMID- 22390862
TI  - Acute and chronic effects of bupivacaine on muscle energetics during contraction
      in vivo: a modular metabolic control analysis.
AB  - Bupivacaine is a widely used anaesthetic injected locally in clinical practice
      for short-term neurotransmission blockade. However, persistent side effects on
      mitochondrial integrity have been demonstrated in muscle parts surrounding the
      injection site. We use the precise language of metabolic control analysis in the
      present study to describe in vivo consequences of bupivacaine injection on muscle
      energetics during contraction. We define a model system of muscle energy
      metabolism in rats with a sciatic nerve catheter that consists of two modules of
      reactions, ATP/PCr (phosphocreatine) supply and ATP/PCr demand, linked by the
      common intermediate PCr detected in vivo by (31)P-MRS (magnetic resonance
      spectroscopy). Measured system variables were [PCr] (intermediate) and
      contraction (flux). We first applied regulation analysis to quantify acute
      effects of bupivacaine. After bupivacaine injection, contraction decreased by
      15.7% and, concomitantly, [PCr] increased by 11.2%. The regulation analysis
      quantified that demand was in fact directly inhibited by bupivacaine (-21.3%),
      causing an increase in PCr. This increase in PCr indirectly reduced mitochondrial
      activity (-22.4%). Globally, the decrease in contractions was almost fully
      explained by inhibition of demand (-17.0%) without significant effect through
      energy supply. Finally we applied elasticity analysis to quantify chronic effects
      of bupivacaine iterative injections. The absence of a difference in elasticities
      obtained in treated rats when compared with healthy control rats clearly shows
      the absence of dysfunction in energetic control of muscle contraction energetics.
      The present study constitutes the first and direct evidence that bupivacaine
      myotoxicity is compromised by other factors during contraction in vivo, and
      illustrates the interest of modular approaches to appreciate simple rules
      governing bioenergetic systems when affected by drugs.

PMID- 22390864
TI  - [Raynaud's syndrome, 2011].
AB  - Raynaud's phenomenon is characterized by intense vasospasm of the digital
      arteries on cold exposure or emotional stress, leading to well-defined colour
      changes in the skin of the fingers. Behind the clinical manifestations, there is
      an imbalance between vasoconstrictor and vasodilator factors. It may be primary
      or secondary to an underlying condition, including autoimmune diseases. Physical
      examination, nail fold capillaroscopy and immunological tests can differentiate
      primary forms from secondary ones. The treatment is based on preventing exposure
      to cold, emotional stress and the administration of certain drugs and, if attacks
      are present, vasodilators, prostaglandin analogues and anticoagulants may be
      given. This review focuses on the characteristics of Raynaud's phenomenon and the
      available diagnostic and therapeutic options.

PMID- 22390863
TI  - Semantic clustering of category fluency in schizophrenia examined with singular
      value decomposition.
AB  - Decreased productivity on verbal fluency tasks by persons with schizophrenia has
      been attributed to semantic system abnormalities. Semantic structure is often
      assessed using multidimensional scaling (MDS) to detect normal and aberrant
      semantic clustering. However, MDS has limitations that may be particularly
      problematic for such assessments. Here, we introduce a different clustering
      technique, singular value decomposition (SVD), to elucidate abnormalities of the
      semantic system in schizophrenia. We compared 102 treated outpatients with
      schizophrenia to 109 healthy adults on two category-cued word fluency tasks.
      Patients with schizophrenia showed semantic clustering patterns that differ
      markedly from those of healthy adults. However, SVD revealed more detailed and
      critical semantic system abnormalities than previously appreciated using MDS.
      Patients with schizophrenia showed less coherent semantic clustering of both low-
      and high-frequency category exemplars than healthy adults. These results suggest
      the intriguing possibility that impaired automatic activation of semantic
      information is a key deficit in schizophrenia.

PMID- 22390865
TI  - [Possibilities of behavior modification in the treatment of diabetes mellitus and
      obesity].
AB  - Being aware of the worldwide spread of diabetes and obesity as well as its
      economic effects, the authors discuss the complex, behavior remediational methods
      of the treatment and its current questions. They emphasize the role of chronic
      stress in the etiopatogenesis of insulin resistance, metabolic syndrome, and type
      2 diabetes. All these require a shift of paradigm in the field of treatment too.
      Based on literature data and on their own practical experience, the authors
      consider that behavior remediational can integrate two, sometimes still opposing
      medical philosophical views in order to foster the efficiency of medical work.
      They review elements of behavior remediation of diabetes, underlining self
      management, acceptance of the illness, and motivation which can be followed by
      teaching theoretical and practical knowledge, the ongoing diabetes education.
      Comorbid psychological disorders impede these processes; their early recognition
      and complex treatment are essential. The authors present a cognitive, behavior
      remediational programme of weight loss, that can be used in practise, both in
      prevention and treatment of diabetes.

PMID- 22390866
TI  - [Effect of treatment with gonadotropin releasing hormone analogues in girls with
      idiopathic central precocious puberty].
AB  - It has been proven for more than two decades that gonadotropin releasing hormone
      analogue therapy is the only choice of treatment in patients with central
      precocious puberty. AIMS: The aim of the authors was to assess the effect of
      gonadotropin releasing hormone analogue treatment on final height, body mass
      index, bone mineral density and ovarian function in girls with idiopathic central
      precocious puberty. METHODS: Predicted adult height, target height and achieved
      height due to therapy was assessed in 15 girls with idiopathic precocious puberty
      treated with gonadotropin releasing hormone analogue. At the beginning of the
      treatment, the age of the girls was 7.0+/-0.8 years (mean+/-SD) and at the end of
      the treatment 12+/-0.8 years. The duration of gonadotropin-releasing hormone
      analogue treatment was 4.48+/-0.8 years. At the time of achieving final height,
      the age of the patients was 18.2+/-2.0 years and the height was 160.4+/-7.1 cm.
      When final height was reached, the authors evaluated bone mineral density Z-score
      values, levels of bone markers and the function of the hypothalamic-pituitary
      gonadal axis. 15 healthy prepubertal girls, 15 pubertal girls and 15 girls who
      reached final height matched for chronological age were selected as control
      groups. RESULTS: The majority of the gonadotropin releasing hormone-treated girls
      reached or almost reached their expected height predicted on the basis of the
      heights of their parents, but the therapy resulted only in a modest beneficial
      effect on height gain. Despite the fact that the body weight of patients
      increased during the treatment, there was no significant difference in their body
      mass index when they reached their final height as compared to controls. As
      compared to controls, patients had a decreased bone mineral density at the time
      when they reached their final height (lumbar spine 2-4 Z score, -0.27+/-1.2 vs.
      0.5+/-0.7 in controls; p = 0.0377), which could be explained by their overweight
      that already existed before treatment, lack of exercise and poor calcium uptake.
      Their menarche occurred 12+/-4.6 months after discontinuing the treatment.
      CONCLUSIONS: Gonadotropin releasing hormone analogue therapy exerts a modest
      beneficial effect on final height gain. There are no detrimental effects on body
      mass index, bone mineral density and ovarian function after treatment. Side
      effects are of minor severity and they are tolerable.

PMID- 22390867
TI  - [Superoxide-anion production by neutrophil granulocytes in healthy and
      preeclamptic pregnant women].
AB  - Data on respiratory burst activity of granulocytes from healthy and preeclamptic
      pregnant women are contradictory. To further investigate a possible role of
      reactive oxygen species in the etiology of preeclampsia, the induced superoxide
      anion generation by granulocytes from non-pregnant, healthy pregnant and
      preeclamptic pregnant women were measured. The reciprocal effects of heat
      inactivated and non-inactivated plasma on superoxide production by neutrophils
      from non-pregnant, healthy pregnant and preeclamptic pregnant subjects were also
      examined. Superoxide generation was measured by ferricytochrome c reduction. Both
      phorbol-12.13-dibutirate- and N-formyl-methionyl-leucyl-phenylalanine-induced
      superoxide production was significantly decreased in normal pregnancy compared to
      results obtained in non-pregnant and preeclamptic pregnant women. Phorbol-12.13
      dibutirate-induced superoxide generation by non-pregnant and preeclamptic
      neutrophils was significantly inhibited by heat-inactivated and non-inactivated
      healthy pregnant plasma. N-formyl-methionyl-leucyl-phenylalanine-stimulated
      superoxide production by non-pregnant and preeclamptic granulocytes was
      suppressed only by non-inactivated healthy pregnant plasma. Phorbol-12.13
      dibutirate-induced superoxide generation of healthy pregnant neutrophils was
      significantly increased by inactivated and non-inactivated non-pregnant and
      preeclamptic plasma. N-formyl-methionyl-leucyl-phenylalanine-stimulated
      superoxide production by healthy pregnant granulocytes was significantly enhanced
      following treatment of the cells with non-inactivated non-pregnant and
      preeclamptic pregnant plasma. Deficient superoxide generation in normal pregnancy
      may be caused by maternal immunosuppressive factors. The failure of reduction in
      superoxide production in preeclampsia may be partly responsible for endothelial
      dysfunction. Apart from oxidative stress, a possible role of inefficient maternal
      immunosuppression should also be considered in the pathogenesis of preeclampsia.

PMID- 22390868
TI  - [Adenoid cystic carcinoma of the uterine cervix].
AB  - This report presents the history of a 35-year-old patient with adenoid cystic
      cervical cancer stage IIIB. Adenoid cystic carcinoma of the uterine cervix is a
      rare disease with poor prognosis. Following irradiation therapy, the patient was
      declared tumor free, and 20 years after diagnosis and treatment, she has no
      pathological signs or symptoms.

PMID- 22390869
TI  - [To the Editors: Role of the physician in the case of out-of-hospital death].

PMID- 22390870
TI  - Systemic virus distribution and host responses in brain and intestine of chickens
      infected with low pathogenic or high pathogenic avian influenza virus.
AB  - BACKGROUND: Avian influenza virus (AIV) is classified into two pathotypes, low
      pathogenic (LP) and high pathogenic (HP), based on virulence in
      chickens.Differences in pathogenicity between HPAIV and LPAIV might eventually be
      related to specific characteristics of strains, tissue tropism and host
      responses. METHODS: To study differences in disease development between HPAIV and
      LPAIV, we examined the first appearance and eventual load of viral RNA in
      multiple organs as well as host responses in brain and intestine of chickens
      infected with two closely related H7N1 HPAIV or LPAIV strains. RESULTS: Both H7N1
      HPAIV and LPAIV spread systemically in chickens after a combined
      intranasal/intratracheal inoculation. In brain, large differences in viral RNA
      load and host gene expression were found between H7N1 HPAIV and LPAIV infected
      chickens. Chicken embryo brain cell culture studies revealed that both HPAIV and
      LPAIV could infect cultivated embryonic brain cells, but in accordance with the
      absence of the necessary proteases, replication of LPAIV was limited.
      Furthermore, TUNEL assay indicated apoptosis in brain of HPAIV infected chickens
      only. In intestine, where endoproteases that cleave HA of LPAIV are available, we
      found minimal differences in the amount of viral RNA and a large overlap in the
      transcriptional responses between HPAIV and LPAIV infected chickens.
      Interestingly, brain and ileum differed clearly in the cellular pathways that
      were regulated upon an AI infection. CONCLUSIONS: Although both H7N1 HPAIV and
      LPAIV RNA was detected in a broad range of tissues beyond the respiratory and
      gastrointestinal tract, our observations indicate that differences in
      pathogenicity and mortality between HPAIV and LPAIV could originate from
      differences in virus replication and the resulting host responses in vital organs
      like the brain.

PMID- 22390871
TI  - Promising option in the prevention of idiopathic anaphylaxis: omalizumab.
AB  - Anaphylaxis is a serious and probably lethal systemic reaction which occurs
      instantaneously after exposure to an allergen. It can occur after exposure to
      various triggers including allergic and non-allergic factors. When a trigger
      cannot be determined, idiopathic anaphylaxis is considered. In idiopathic
      anaphylaxis presenting with frequent attacks, long-term prophylaxis with H(1)
      antihistamine and steroid treatment are recommended. Omalizumab, a humanized
      monoclonal antibody drug which decreases free immunoglobulin E molecules in the
      circulation, is approved for the treatment of chronic severe persistent allergic
      asthma. We report a 46-year-old female patient with severe uncontrolled allergic
      asthma and idiopathic anaphylaxis presenting with attacks of abdominal pain,
      generalized urticaria, feeling of strangulation in her throat and
      unconsciousness. Omalizumab at a dose of 375 mg once every 2 weeks was
      administrated and at the end of 3 months anaphylactic attacks had ceased. At the
      end of the sixth month of omalizumab therapy, her injection intervals were
      extended to 4 weeks. After she began experiencing moderate attacks of urticaria
      and hoarsening, however, initial treatment plan was reestablished. Currently, she
      has completed her first year of treatment without further attacks.

PMID- 22390872
TI  - Interpreting NK cell transcripts versus T cell transcripts in renal transplant
      biopsies.
AB  - NK cell transcripts are increased in biopsies with antibody-mediated rejection,
      whereas T cell transcripts are increased in T cell-mediated rejection. However,
      NK and T cells share many features, creating potential ambiguity. Therefore to
      estimate the NK- versus T cell transcript burdens separately, we defined
      nonoverlapping transcripts selective for NK cells (N = 4) or T cells (N = 5). We
      compared NK- versus T cell transcript burdens in microarrays from 403 kidney
      transplant biopsies (182 early, 221 late). In late biopsies, high NK-cell
      transcript expression was associated with antibody-mediated rejection,
      correlating with microvascular inflammation and donor specific HLA antibody.
      However, some early biopsies with T cell-mediated rejection had high NK-cell
      transcript expression, as well as T cell transcripts, without evidence of
      antibody-mediated rejection or DSA, correlating with interstitial inflammation
      and tubulitis. Both NK-cell and T cell transcripts were moderately increased in
      many kidneys with inflammation secondary to injury or atrophy scarring. These
      results support the distinct role of NK cells in late antibody-mediated
      rejection, but indicate a role for NK-transcript expressing cells (NK cells or T
      cells with NK features) both in T cell-mediated rejection and in inflammation
      associated with injury and atrophy scarring.

PMID- 22390874
TI  - Interaction of 8-anilinonaphthalene 1-sulphonate (ANS) and human matrix
      metalloproteinase 7 (MMP-7) as examined by MMP-7 activity and ANS fluorescence.
AB  - Human matrix metalloproteinase 7 (MMP-7) is the smallest matrix
      metalloproteinase. It plays important roles in tumour invasion and metastasis. 8
      Anilinonaphthalene 1-sulphonate (ANS) is a fluorescent probe widely used for the
      analysis of proteins. It emits large fluorescence energy when its
      anilinonaphthalene group binds with hydrophobic regions of protein. In this
      study, we analysed the interaction of ANS and MMP-7. At pH 4.5-9.5, ANS inhibited
      MMP-7 activity in the hydrolysis of (7-methoxycoumarin-4-yl)acetyl-L-Pro-L-Leu
      Gly-L-Leu-[N(3)-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl]-L-Ala-L-Arg-NH(2).
      The inhibition was a non-competitive manner and depended on the time for pre
      incubation of ANS and MMP-7. At pH 4.5-9.5, the fluorescence of ANS was not
      changed by the addition of MMP-7. At pH 3.5, MMP-7 lacked activity, and the
      fluorescence of ANS was increased by the addition of MMP-7. These results suggest
      that at pH 4.5-9.5, the sulphonic group of ANS binds with MMP-7 through
      electrostatic interaction, whereas at pH 3.5, the anilinonaphthalene group of ANS
      binds with MMP-7 through hydrophobic interaction.

PMID- 22390873
TI  - Network biology methods integrating biological data for translational science.
AB  - The explosion of biomedical data, both on the genomic and proteomic side as well
      as clinical data, will require complex integration and analysis to provide new
      molecular variables to better understand the molecular basis of phenotype.
      Currently, much data exist in silos and is not analyzed in frameworks where all
      data are brought to bear in the development of biomarkers and novel functional
      targets. This is beginning to change. Network biology approaches, which emphasize
      the interactions between genes, proteins and metabolites provide a framework for
      data integration such that genome, proteome, metabolome and other -omics data can
      be jointly analyzed to understand and predict disease phenotypes. In this review,
      recent advances in network biology approaches and results are identified. A
      common theme is the potential for network analysis to provide multiplexed and
      functionally connected biomarkers for analyzing the molecular basis of disease,
      thus changing our approaches to analyzing and modeling genome- and proteome-wide
      data.

PMID- 22390875
TI  - Bovine pericardium based non-cross linked collagen matrix for successful root
      coverage, a clinical study in human.
AB  - INTRODUCTION: The aim of this study was to clinically assess the capacity of a
      novel bovine pericardium based, non-cross linked collagen matrix in root
      coverage. METHODS: 62 gingival recessions of Miller class I or II were treated.
      The matrix was adapted underneath a coronal repositioned split thickness flap.
      Clinical values were assessed at baseline and after six months. RESULTS: The mean
      recession in each patient was 2.2 mm at baseline. 6 Months after surgery 86.7% of
      the exposed root surfaces were covered. On average 0,3 mm of recession remained.
      The clinical attachment level changed from 3.5 +/- 1.3 mm to 1,8 ( +/- 0,7) mm
      during the observational time period. No statistically significant difference was
      found in the difference of probing depth. An increase in the width of gingiva was
      significant. With a baseline value of 1.5 +/- 0.9 mm an improvement of 2.4 +/-
      0.8 mm after six month could be observed. 40 out of 62 recessions were considered
      a thin biotype at baseline. After 6 months all 62 sites were assessed thick.
      CONCLUSIONS: The results demonstrate the capacity of the bovine pericardium based
      non-cross linked collagen matrix for successful root coverage. This material was
      able to enhance gingival thickness and the width of keratinized gingiva. The
      percentage of root coverage achieved thereby is comparable to existing
      techniques. This method might contribute to an increase of patient's comfort and
      an enhanced aesthetical outcome.

PMID- 22390876
TI  - The contributions of self-reported injury characteristics and psychiatric
      symptoms to cognitive functioning in OEF/OIF veterans with mild traumatic brain
      injury.
AB  - Mild traumatic brain injury (mTBI) affects a significant number of combat
      veterans returning from Operation Enduring Freedom/Operation Iraqi Freedom
      (OEF/OIF). Although resolution of mTBI symptoms is expected over time, some
      individuals continue to report lingering cognitive difficulties. This study
      examined the contributions of self-reported mTBI injury characteristics (e.g.,
      loss of consciousness, post-traumatic amnesia) and psychiatric symptoms to both
      subjective and objective cognitive functioning in a sample of 167 OEF/OIF
      veterans seen in a TBI clinic. Injury characteristics were not associated with
      performance on neuropsychological tests but were variably related to subjective
      ratings of cognitive functioning. Psychiatric symptoms were highly prevalent and
      fully mediated most of the relationships between injury characteristics and
      cognitive ratings. This indicates that mTBI characteristics such as longer time
      since injury and loss of consciousness or post-traumatic amnesia can lead to
      increased perceived cognitive deficits despite having no objective effects on
      cognitive performance. Psychiatric symptoms were associated with both cognitive
      ratings and neuropsychological performance, illustrating the important role that
      psychiatric treatment can potentially play in optimizing functioning. Finally,
      subjective cognitive ratings were not predictive of neuropsychological
      performance once psychiatric functioning was statistically controlled, suggesting
      that neuropsychological assessment provides valuable information that cannot be
      gleaned from self-report alone.

PMID- 22390877
TI  - The world comes to Glasgow--the IRPA 13 Congress.

PMID- 22390878
TI  - Development of web-based computer-tailored advice to promote physical activity
      among people older than 50 years.
AB  - BACKGROUND: The Active Plus project is a systematically developed theory- and
      evidence-based, computer-tailored intervention, which was found to be effective
      in changing physical activity behavior in people aged over 50 years. The process
      and effect outcomes of the first version of the Active Plus project were
      translated into an adapted intervention using the RE-AIM framework. The RE-AIM
      model is often used to evaluate the potential public health impact of an
      intervention and distinguishes five dimensions: reach, effectiveness, adoption,
      implementation, and maintenance. OBJECTIVE: To gain insight into the systematic
      translation of the first print-delivered version of the Active Plus project into
      an adapted (Web-based) follow-up project. The focus of this study was on the
      reach and effectiveness dimensions, since these dimensions are most influenced by
      the results from the original Active Plus project. METHODS: We optimized the
      potential reach and effect of the interventions by extending the delivery mode of
      the print-delivered intervention into an additional Web-based intervention. The
      interventions were adapted based on results of the process evaluation, analyses
      of effects within subgroups, and evaluation of the working mechanisms of the
      original intervention. We pretested the new intervention materials and the Web
      based versions of the interventions. Subsequently, the new intervention
      conditions were implemented in a clustered randomized controlled trial. RESULTS:
      Adaptations resulted in four improved tailoring interventions: (1) a basic print
      delivered intervention, (2) a basic Web-based intervention, (3) a print-delivered
      intervention with an additional environmental component, and (4) a Web-based
      version with an additional environmental component. Pretest results with
      participants showed that all new intervention materials had modest usability and
      relatively high appreciation, and that filling in an online questionnaire and
      performing the online tasks was not problematic. We used the pretest results to
      improve the usability of the different interventions. Implementation of the new
      interventions in a clustered randomized controlled trial showed that the print
      delivered interventions had a higher response rate than the Web-based
      interventions. Participants of both low and high socioeconomic status were
      reached by both print-delivered and Web-based interventions. CONCLUSIONS:
      Translation of the (process) evaluation of an effective intervention into an
      adapted intervention is challenging and rarely reported. We discuss several major
      lessons learned from our experience. TRIAL REGISTRATION: Nederlands Trial
      Register (NTR): 2297;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2297 (Archived by
      WebCite at http://www.webcitation.org/65TkwoESp).

PMID- 22390879
TI  - Phencyclidine/schizophrenia: one view toward the past, the other to the future.
AB  - The history of the chemical synthesis and animal/human pharmacology of
      phencyclidine is documented. From its early use as a general anesthetic, chemical
      model of schizophrenia, and drug of abuse, phencyclidine has had a checkered
      history. Research with this agent and its chemical derivatives like ketamine have
      provided a solid foundation for just a beginning to understanding the
      neuropathology of schizophrenia.

PMID- 22390880
TI  - First- and second-line anti-tuberculosis drug resistance in Northwest Ethiopia.
AB  - SETTING: Gondar Hospital, Gondar Health Centre, Metemma Hospital, Bahir Dar
      Hospital and Debre Markos Hospital in Northwest Ethiopia. OBJECTIVE: To assess
      the level of and risk factors for first- and second-line drug resistance among
      tuberculosis (TB) patients. DESIGN: Drug susceptibility  testing (DST) against
      first-line drugs, including isoniazid (INH), rifampicin (RMP), streptomycin (SM),
      ethambutol (EMB) and pyrazinamide (PZA), was performed using the BacT/ALERT 3D
      system. DST against second-line drugs, including fluoroquinolones and
      aminoglycocides/cyclic peptides, was  performed using GenoType MTBDRsl. RESULTS:
      Of 260 Mycobacterium tuberculosis isolates, 41 (15.8%) were resistant to at least
      one first-line drug, 13 (5.0%) were multidrug-resistant (MDR) and 9 (3.5%) were
      resistant to all first-line drugs. Any resistance to INH, RMP, SM, EMB and  PZA
      was respectively 36 (13.8%), 15 (5.8%), 26 (10.0%), 19 (7.3%) and 12 (4.6%). Of
      214 new and 46 previously treated cases, respectively 8 (3.7%) and 5 (10.9%) were
      MDR. All isolates were susceptible to all second-line drugs. CONCLUSION: A
      substantial number of new and previously treated  cases harbour MDR-TB. We
      recommend DST at least for previously treated cases, patients who remain smear
      positive at the end of the second month of treatment and patients in close
      contact with MDR-TB cases. Improved infection control measures need to be
      implemented in Ethiopia.

PMID- 22390881
TI  - Fatal rectal perforation following boar-to-boar mounting.
AB  - Although abnormal sexual behavior, including boar-to-boar mounting with anal
      penetration, is recognized in pubescent pigs, reports of the pathologic
      consequences are scarce. A 7-month-old male minipig, housed with age-matched
      males, died within 1 day of the onset of lethargy and reluctance to rise. At
      necropsy, 2 rectal tears were identified as the cause for fibrinous peritonitis,
      and spermatozoa were identified in the pelvic and peritoneal cavity by light and
      transmission electron microscopy. According to DNA typing results, using 11
      porcine microsatellites, the intraperitoneal semen was from at least 2 pen mates.
      The prohibition of castration of fattening pigs, implemented or planned in
      multiple European countries, could increase the risk of rectal perforation in co
      housed pigs.

PMID- 22390882
TI  - Evidence of oxidative injury of the spinal cord in 2 horses with equine
      degenerative myeloencephalopathy.
AB  - The cervical spinal cords of 2 horses with equine degenerative
      myeloencephalopathy (EDM) were evaluated for evidence of oxidative damage to the
      central nervous system (CNS) using immunohistochemical staining for 3
      nitrotyrosine (3-NT) and 4-hydroxynonenol (4-HNE). Neurons of the CNS from horses
      with EDM had positive immunohistochemical staining, whereas control samples did
      not, thus supporting the theory that oxidative damage is a potential underlying
      factor in horses with EDM. In addition, serum vitamin E concentration was low in
      both EDM-affected horses, and vitamin E concentration was also deficient in the
      cerebrospinal fluid in 1 EDM horse, further supporting the association between
      low vitamin E concentrations and oxidative damage to the CNS. Continued research
      is necessary to further define the pathophysiologic mechanisms of EDM.

PMID- 22390883
TI  - White matter predictors of cognitive functioning in older adults.
AB  - Few studies have applied multiple imaging modalities to examine cognitive
      correlates of white matter. We examined the utility of T2-weighted magnetic
      resonance imaging (MRI) -derived white matter hyperintensities (WMH) and
      diffusion tensor imaging-derived fractional anisotropy (FA) to predict cognitive
      functioning among older adults. Quantitative MRI and neuropsychological
      evaluations were performed in 112 older participants from an ongoing study of the
      genetics of Alzheimer's disease (AD) in African Americans. Regional WMH volumes
      and FA were measured in multiple regions of interest. We examined the association
      of regional WMH and an FA summary score with cognitive test performance.
      Differences in WMH and FA were compared across diagnostic groups (i.e., normal
      controls, mild cognitive impairment, and probable AD). Increased WMH volume in
      frontal lobes was associated with poorer delayed memory performance. FA did not
      emerge as a significant predictor of cognition. White matter hyperintensity
      volume in the frontal and parietal lobes was increased in MCI participants and
      more so in AD patients relative to controls. These results highlight the
      importance of regionally distributed small vessel cerebrovascular disease in
      memory performance and AD among African American older adults. White matter
      microstructural changes, quantified with diffusion tensor imaging, appear to play
      a lesser role in our sample.

PMID- 22390884
TI  - Prospective blind comparative clinical study of two point fixation of zygomatic
      complex fracture using wire and mini plates.
AB  - BACKGROUND: The zygomatic maxillary complex (ZMC) fractures are one of the most
      frequent injuries of the facial skeleton due to its position and facial contour.
      Assaults, road traffic accidents and falls are the principal etiologic factors
      that may cause fractures of zygomatic bone. The different fixation methods are
      applied to treat the zygomatic bone fractures, with many more classifications
      which have been described in the literature for the ease of management. The type
      of the fracture, its severity and associated facial fractures usually interferes
      the treatment modality. PURPOSE OF STUDY: The aim of this paper is to show the
      results of 18yrs prospective blind comparative study using wire and plate
      osteosynthesis which needed open reduction and internal fixation involving Type
      II to Type IV Spissel and Schroll ZMC fractures. MATERIALS AND METHODS: Total 80
      cases included in the study out of 1780 ZMC cases which were treated using wire
      and plate osteosynthesis over a period of 18 yrs, involving only Type II to Type
      IV Spissel and Schroll ZMC fractures. Other types excluded from study to prevent
      observer bias. All the fixations carried out through Standard Dingman's incision
      using stainless steel 26 gauze wire and titanium 1.5 mm mini plate system under
      general anesthesia by single maxillofacial surgeon and evaluated by another
      maxillofacial surgeon who is blinded for surgical procedure after 2 and 4 wks of
      follow-up for facial symmetry, wound healing, functional assessment (mouth
      opening, diplopia), and sensory disturbance. All the data tabulated in Excel
      software (Microsoft) for statistical analysis. P-value calculated to know the
      Significance of treatment modality in all aspects. RESULTS: Result shows no
      significant p-values indicating both the operating techniques are equally
      efficient in the surgical management of ZMC fracture. CONCLUSION: Osteosynthesis
      by mini plates is simple, logical and effective treatment compared to wire
      osteosynthesis in regard to stability of fracture fragments. Wire osteosynthesis
      will be helpful in emergency surgeries or where the mini plates are not
      available. Even though the wire osteosynthesis is economical compared to mini
      plate fixation; but the time and skill is required for fixation of wires.

PMID- 22390885
TI  - Personnel dosimetry in UK radiology: is it time for a change?

PMID- 22390887
TI  - Special issue on sorption and transport processes affecting the fate of
      environmental pollutants in the subsurface.

PMID- 22390886
TI  - Initial and sustained participation in an internet-delivered long-term worksite
      health promotion program on physical activity and nutrition.
AB  - BACKGROUND: Determinants of participation in health promotion programs are
      largely unknown. To evaluate and implement interventions, information is needed
      regarding their reach as well as regarding the characteristics of program users
      and non-users. OBJECTIVE: In this study, individual, lifestyle, and health
      indicators were investigated in relation to initial, and sustained participation
      in an Internet-delivered physical activity and healthy nutrition program in the
      workplace setting. In addition, determinants of program website use were studied.
      METHODS: Determinants of participation were investigated in a longitudinal study
      among employees from six workplaces participating in a two-year cluster
      randomized controlled trial. The employees were invited by email to participate.
      At baseline, all participants visited a website to fill out the questionnaire on
      lifestyle, work, and health factors. Subsequently, a physical health check was
      offered, followed by face-to-face advice. Throughout the study period, all
      participants had access to a website with information on lifestyle and health,
      and to fully automated personalized feedback on the questionnaire results. Only
      participants in the intervention received monthly email messages to promote
      website visits during the first year and had access to additional Web-based tools
      (self-monitors, a food frequency questionnaire assessing saturated fat intake,
      and the possibility to ask questions) to support behavior change. Website use was
      monitored by website statistics measuring access. Logistic regression analyses
      were conducted to identify characteristics of employees who participated in the
      program and used the website. RESULTS: Complete baseline data were available for
      924 employees (intervention: n=456, reference: n=468). Lifestyle and health
      factors were not associated with initial participation. Employees aged 30 years
      and older were more likely to start using the program and to sustain their
      participation. Workers with a low intention to increase their physical activity
      level were less likely to participate (Odds Ratio (OR)=0.60, 95% Confidence
      interval (95%CI), 0.43-0.85) but more likely to sustain participation throughout
      the study period (ORs ranging from 1.40 to 2.06). Furthermore, it was found that
      smokers were less likely to sustain their participation in the first and second
      year (OR=0.54, 95%CI 0.35-0.82) and to visit the website (OR=0.72, 95%CI 0.54
      0.96). Website use was highest in the periods immediately after the baseline
      (73%) and follow-up questionnaires (71% and 87%). Employees in the intervention
      were more likely to visit the website in the period they received monthly emails
      (OR=5.88, 95%CI 3.75-9.20) but less likely to visit the website in the subsequent
      period (OR=0.62, 95%CI 0.45-0.85). CONCLUSIONS: Modest initial participation and
      high attrition in program use were found. Workers with a low intention to change
      their behavior were less likely to participate, but once enrolled they were more
      likely to sustain their participation. Lifestyle and health indicators were not
      related to initial participation, but those with an unhealthy lifestyle were less
      likely to sustain. This might influence program effectiveness. Regular email
      messages prompted website use, but the use of important Web-based tools was
      modest. There is a need for more appealing techniques to enhance retention and to
      keep those individuals who need it most attracted to the program. TRIAL
      REGISTRATION: ISRCTN52854353; http://www.controlled-trials.com/ISRCTN52854353.

PMID- 22390888
TI  - Profuse sialorrhea in a case of anti N-methyl-D-aspartate receptor (NMDAR)
      encephalitis.

PMID- 22390889
TI  - An easy adjustable method of ectatic vertebrobasilar artery transposition for
      microvascular decompression.
AB  - BACKGROUND: Microvascular decompression (MVD) of trigeminal neuralgia (TN) or
      hemifacial spasm (HFS) caused by an elongated, tortuous or enlarged vertebral or
      basilar artery has a higher rate of incomplete cure. OBJECTIVE: We used an easily
      applied and adjustable method of vertebrobasilar artery transposition and
      fixation to improve the immediate surgical outcome of MVD of TN or HFS due to
      compression by an ectatic vertebrobasilar artery system. METHODS: Vertebral or
      basilar artery transposition was performed using the vascular sling with a strip
      of unabsorbable dural tape. The vertebrobasilar artery-sling complex was then
      fixed to the dura over the petrous bone by aneurysm clip through the dural
      bridge. The direction and angle of traction on the vertebrobasilar artery was
      adjustable using different lengths of clip or the horizontal level of the dural
      bridge. RESULTS: The sling and clip fixation method has been applied in 7 cases
      of MVD associated with vertebral or basilar artery compression. All 3 patients
      with TN and one with HFS had total remission of symptoms right after the
      procedure; one patient was completely free of spasm within 1 week after MVD and
      one had achieved 80% improvement of spasm in his last clinical visit 3 months
      after MVD. There was no major surgical complication in these 7 patients.
      Surprisingly, refractory hypertension was unexpectedly cured in one patient with
      TN following the procedure. CONCLUSION: The vertebrobasilar artery transposition
      and fixation method used in the present study provided surgeons an easy and
      adjustable way to perform MVD safely and effectively.

PMID- 22390890
TI  - Normal height and weight in a series of ambulant Duchenne muscular dystrophy
      patients using the 10 day on/10 day off prednisone regimen.
AB  - Prednisone treatment delays the progressive course of Duchenne muscular
      dystrophy. The aim of this study was to determine the influence of the 10 day
      on/10 day off treatment on height and weight. We retrospectively reviewed the
      growth and weight charts of Duchenne patients born between 1988 and 2006
      (patients between 4 and 9 years old, being able to walk in the home situation).
      Forty-seven patients were eligible for further analysis and divided into two
      groups: 33 patients treated with prednisone and 14 non-prednisone treated
      patients. Results of a median follow-up of 57 months (range 27-146) are
      described. By using linear mixed models this study demonstrates that height and
      body mass index in prednisone-treated patients with 10/10 regimen are not
      significantly different compared to untreated patients. We cautiously conclude
      that the alternating prednisone regimen has no apparent side effects on weight
      and height in the ambulatory phase of Duchenne muscular dystrophy.

PMID- 22390891
TI  - [Case 46. Tolosa-Hunt syndrome].

PMID- 22390893
TI  - The built environment and obesity among low-income preschool children.
AB  - In spite of the evidence that adult obesity is influenced by environmental
      factors, the influence of the environment on childhood obesity remains under
      investigated. This paper examines the association of the built environment with
      the prevalence of obesity in low-income preschool children. Built environment
      indicators include measures relating to food choice and physical activity. The
      relationship of the environment with childhood obesity is further stratified by
      urban-rural location. Overall, the built environment is associated with the
      prevalence of obesity in low-income preschool children, although the impact of
      the environment is affected by urban-rural status. Results imply broad-scope for
      community-level interventions.

PMID- 22390894
TI  - Role of Sulindac and Celecoxib in chemoprevention of colorectal cancer via
      intrinsic pathway of apoptosis: exploring NHE-1, intracellular calcium
      homeostasis and Calpain 9.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) have become promising agents for
      the chemoprevention of colorectal cancer presumably by inducing apoptosis.
      However, the role of NSAIDs in the regulation of NHE-1, intracellular calcium
      [Ca(2+)](i) homeostasis and Calpain 9 signaling pathway seems unclear. Male
      Sprague-Dawley rats were used as model for experimental colorectal cancer.
      Effects of pro-carcinogen (DMH) and NSAIDs were studied via morphological
      examination of tumors, histopathological changes, [Ca(2+)](i) homeostasis,
      production of reactive oxygen species (ROS), changes in mitochondrial membrane
      potential (MMP or DeltaPsi(M)) and expression profile of target genes and
      proteins both at transcription and translation levels respectively. Size and
      number of tumors were found less in NSAIDs co-administered groups as compared to
      the DMH alone. Higher expression of NHE-1 was observed in DMH group whereas
      Calpain 9 was up-regulated in NSAIDs co-administered groups. [Ca(2+)](i) levels
      and reactive oxygen species were observed elevated in NSAIDs co-administered
      groups. DeltaPsi(M) was found higher in DMH alone group along with the increased
      expression of the anti-apoptotic and mitochondrial membrane guard protein, Bcl-2.
      Expression levels of various pro-apoptotic proteins were observed higher in case
      of NSAIDs co-administered groups. Down-regulation of NHE-1, along with an
      increased [Ca(2+)](i) and induction of intrinsic pathway of apoptosis via
      activated Calpain 9 could be a putative mechanism pursued by Sulindac and
      Celecoxib for the chemoprevention of colorectal cancer.

PMID- 22390895
TI  - Changes in composition of colostrum of Egyptian buffaloes and Holstein cows.
AB  - BACKGROUND: Changes in colostrum composition of Egyptian buffaloes and Holstein
      cows collected at calving, 6, 12, 24, 48, 72, 96, 120 h and after 14 days of
      parturition were studied. Total solids, total protein, whey proteins, fat,
      lactose and ash contents were determined. Macro- and micro-elements, IgG, IgM,
      IGF-1, lactoferrin and vitamins (A and E) were also estimated. RESULTS: At
      calving, the total protein and whey proteins concentration did not differ between
      buffalo and cow colostrum, while total solids, fat, lactose and ash
      concentrations were higher in buffalo than in cow colostrum. All components
      decreased gradually as the transition period advanced except lactose which
      conversely increased. On the fifth day post-partum, concentration of total
      protein, whey proteins, fat, ash and total solids decreased by 69.39, 91.53,
      36.91, 45.58 and 43.85% for buffalo and by 75.99, 94.12, 53.36, 33.59 and 52.26%
      for cow colostrum. However, lactose concentration increased by 42.45% for buffalo
      and 57.39% for cow colostrum. The macro-and micro-elements concentration of both
      colostrums tended to decline slightly toward normality on the fifth day of
      parturition. Buffalo colostrum had a higher concentration of vitamin E than cow
      colostrum during the experimental period. At calving, the concentration of
      vitamin A in buffalo colostrum was found to be approximately 1.50 times lower
      than in cow colostrum. The concentrations of IgG, IgM, IGF-1 and lactoferrin
      decreased by 97.90, 97.50, 96.25 and 96.70% for buffalo and 76.96, 74.92, 76.00
      and 77.44% for cow colostrum, respectively after five days of parturition.
      CONCLUSIONS: There is a dramatic change in buffalo and cow colostrum composition
      from the first milking until the fifth day of parturition. There are differences
      between buffalo and cow colostrum composition during the five days after calving.
      The composition of both colostrums approaches to those of normal milk within five
      days after parturition.

PMID- 22390896
TI  - Obesogenic neighbourhoods: the impact of neighbourhood restaurants and
      convenience stores on adolescents' food consumption behaviours.
AB  - OBJECTIVE: To examine the relationship between the neighbourhood food environment
      and dietary intake among adolescents. DESIGN: Cross-sectional design using: (i) a
      geographic information system to assess characteristics of the neighbourhood food
      environment and neighbourhood socio-economic status; (ii) the modified Healthy
      Eating Index (HEI) to assess participants' overall diet quality; and (iii)
      generalized linear models to examine associations between HEI and home and school
      food environmental correlates. SETTING: Mid-sized Canadian city in Ontario,
      Canada. Participants Grade 7 and 8 students (n 810) at twenty-one elementary
      schools. RESULTS: Students living in neighbourhoods with a lower diversity of
      land-use types, compared with their higher diversity counterparts, had higher HEI
      scores (P < 0.05). Students with more than 1 km between their home and the
      nearest convenience store had higher HEI scores than those living within 1 km (P
      < 0.01). Students attending schools with a distance further than 1 km from the
      nearest convenience store (P < 0.01) and fast-food outlet (P < 0.05) had higher
      HEI scores than those within 1 km. Those attending schools with three or more
      fast-food outlets within 1 km had lower HEI scores than those attending schools
      with no fast-food outlet in the school surroundings (P < 0.05). CONCLUSIONS:
      Close proximity to convenience stores in adolescents' home environments is
      associated with low HEI scores. Within adolescents' school environments, close
      proximity to convenience and fast-food outlets and a high density of fast-food
      outlets are associated with low HEI scores.

PMID- 22390897
TI  - 22 : 6n-3 DHA inhibits differentiation of prostate fibroblasts into
      myofibroblasts and tumorigenesis.
AB  - Prostate cancer is one of the most common malignancies in men. Epidemiological
      and experimental studies have revealed that stromal cells of the tumour
      microenvironment contribute to the development of prostate cancers, while long
      chain n-3 PUFA-enriched diets reduce the risk of this tumour histotype. These
      findings prompted us to investigate whether DHA, an n-3 PUFA, may abrogate
      differentiation of prostate fibroblasts into myofibroblasts, the activated form
      of fibroblasts generally involved in prostate cancer progression. We used the
      human prostate carcinoma cell line (PC3) as a prostate adenocarcinoma model and
      found that DHA (1) inhibits alpha-smooth muscle actin (alpha-SMA) expression, a
      typical marker of myofibroblast differentiation, in prostate fibroblasts
      stimulated in vitro with transforming growth factor-beta (TGF-beta), (2) blocks
      the matrix metalloproteinase-2-dependent enhanced invasiveness of PC3 prostate
      adenocarcinoma cells migrated in a medium conditioned by TGF-beta-stimulated
      prostate fibroblasts, (3) prevents epithelial-mesenchymal transition (EMT) and
      invasiveness of PC3 cells promoted by a medium conditioned by TGF-beta-stimulated
      prostate fibroblasts, and (4) reduces the growth rate of tumours obtained in
      immunodeficient animals injected with PC3 cells plus TGF-beta-stimulated prostate
      fibroblasts. Moreover, DHA was found to revert alpha-SMA expression and the
      invasiveness-promoting activity exerted in PC3 cells by tumoral-activated
      fibroblasts. Thus, DHA represents a suitable agent to inhibit prostate
      myofibroblast differentiation, invasiveness and EMT, two most important tumour
      promoting activities involved in the progression of prostate cancer cells.

PMID- 22390898
TI  - Propofol hemisuccinate suppresses cortical spreading depression.
AB  - Propofol is a rapidly acting water-insoluble non-barbiturate anesthetic agent
      that is widely used as an intravenous sedative-hypnotic agent. Anecdotal evidence
      indicates that propofol may be effective at terminating intractable migraine
      headache. Cortical spreading depression (CSD) is believed to be the neural
      correlate of migraine aura and may be a trigger for migraine pain. Agents that
      block the induction or slow the spread of CSD may be of utility in treating
      migraine. Here we examined the ability of propofol hemisuccinate (PHS), a water
      soluble prodrug of propofol, to affect CSD in mice. For comparison, we examinined
      dizocilpine, an NMDA receptor antagonist, that is well recognized to inhibit CSD.
      When administered 15min prior to activation of CSD by KCl application to the
      cortex, intraperitoneal PHS at doses of 120 and 200mg/kg decreased the number of
      CSD deflections without an effect on CSD amplitude, and at 200mg/kg caused a 77%
      reduction in CSD velocity. The minimally-effective dose of PHS (120mg/kg) did not
      cause sedation or motor impairment and while some animals receiving 200mg/kg did
      demonstrate motor impariment none exhibited loss-of-righting reflex (anesthesia).
      Dizocilpine produced comparable inhibition of CSD at doses of 0.5 and 2.5mg/kg.
      We conclude that acute PHS treatment inhibits CSD. Our results indicate that
      propofol, or its prodrug PHS, are worthy of further investigation as a treatment
      for migraine.

PMID- 22390899
TI  - Periaqueductal gray stimulation suppresses spontaneous pain behavior in rats.
AB  - Methods for evaluating analgesic effect for spontaneous pain are increasingly
      important because it is reported by most patients with neuropathic pain. The
      present study assessed the analgesic effects of periaqueductal gray (PAG)
      stimulation in the spared nerve injury (SNI) model of neuropathic pain of the
      rat. Spontaneous rapid paw withdrawal movements were used as the index of
      spontaneous pain. Deep-brain stimulation in the PAG was performed in rats 3 weeks
      after SNI. Significant analgesic effects on spontaneous pain behavior were
      observed at the same stimulation parameter that reversed the reduced mechanical
      threshold of the von Frey test. Both analgesic effects lasted 30-40min beyond the
      3min stimulation period. In summary, PAG stimulation was effective in alleviating
      spontaneous pain and mechanical allodynia in the SNI rat. The frequency of
      spontaneous paw lifting, a behavioral index of spontaneous pain used in this
      study, will be useful for future testing of therapeutic methods.

PMID- 22390900
TI  - Allicin ameliorates cognitive deficits ageing-induced learning and memory
      deficits through enhancing of Nrf2 antioxidant signaling pathways.
AB  - Numerous studies have demonstrated that learning and memory abilities in the
      course of normal aging cognitive abilities tend to decline and Nrf2 expression
      appears to decline with aging. So, Nrf2 pathway has been identified as a
      promising therapeutic target for neurodegenerative diseases. The organosulfur
      compounds, allicin can activate Nrf2, because it has an electrophilic center,
      which can serve as an attack site for nucleophiles, such as specific protein
      sulfhydryl groups present on Keap1. However, the influence of allicin on aging
      induced cognitive deficits has not been examined. In this study, we assess the
      effects of allicin on endogenous antioxidant defenses in hippocampus of
      cognitively impaired aged mouse. Our results indicate that treatment of allicin
      significantly ameliorated ageing-induced cognitive dysfunction through enhancing
      of Nrf2 antioxidant signaling pathways. Therefore, allicin could be recommended
      as a possible candidate for the prevention and therapy of cognitive deficits in
      aging and Alzheimer's disease.

PMID- 22390901
TI  - The "pegylated" story continues--perhaps because both ends (alpha2a and alpha2b)
      are true?

PMID- 22390902
TI  - Congenital cholesteatoma isolated to the mastoid presenting as stricture of the
      external auditory canal.
AB  - Congenital cholesteatoma may originate at various sites in the temporal bone.
      Congenital cholesteatoma of the mastoid origin shows a variable clinical
      presentation, although the least common site is the mastoid process. We report an
      extremely rare case of congenital cholesteatoma isolated to the mastoid
      presenting as stricture of the external auditory canal. A 10-year-old boy
      presented with stricture of the left-sided external auditory canal caused by
      bulging of the posterior wall of the external auditory canal. Computed tomography
      showed destruction of the posterior wall of the external auditory canal by a
      lesion of soft tissue density in the left mastoid cells. At surgery,
      cholesteatoma was observed in the mastoid cavity. Although destruction of the
      posterior wall of the external auditory canal was identified, the external
      auditory canal skin and tympanic membrane were intact, and the aditus ad antrum
      mucosa was normal. Congenital cholesteatoma isolated to the mastoid was
      diagnosed. Diagnosis of congenital cholesteatoma isolated to the mastoid should
      be based on clinical examination, radiological evaluation, and surgical findings.
      In addition, the possibility of congenital cholesteatoma isolated to the mastoid
      should be considered in patients with stricture of the external auditory canal.

PMID- 22390903
TI  - Malondialdehyde level and adenosine deaminase activity in adenoid tissue of
      patients with OME and obstructive adenoid hypertrophy.
AB  - OBJECTIVE: The aim of our study was to determine and compare adenosine deaminase
      (ADA) activity and malondialdehyde (MDA) level in adenoid tissue of patients with
      or without otitis media with effusion (OME). METHODS: The study included 30
      patients undergoing adenoidectomy due to obstructive adenoid hypertrophy (OAH) or
      OME. Tissue MDA level was measured by the method of Okawa with modification and
      tissue ADA activity by the method of Giusti. We measured, superoxide dismutase
      (SOD) and catalase (CAT) activities as well. RESULTS: In patients with OAH, mean
      tissue MDA level and ADA activity were 4.13 +/- 0.90 nmol/mg Pr and 0.39 +/- 0.04
      U/mg Pr, respectively, which were significantly higher than those of OME group
      (1.43 +/- 0.41 nmol/mg Protein and 0.22 +/- 0.04 U/mg Pr, respectively) (P<0.05).
      SOD and CAT activities were found to be increased in patients with OAH when
      compared to the OME group but they did not reach statistically significant level
      (P=0.06 and 0.05 respectively). CONCLUSIONS: The present study showed the
      presence of measurable ADA activity in adenoid tissue, and also significant
      increases in both tissue MDA level and ADA activity in OAH tissue when compared
      to adenoid tissue of the patient with OME. However, the significance of changes
      in MDA and ADA activation in the pathogenesis of OAH requires further study.

PMID- 22390904
TI  - Bone anchored hearing aids in children: an update.
AB  - OBJECTIVE: Over recent years, there have been a significant number of
      publications reporting evolving bone anchored hearing device (BAHD) indications
      and modifications in surgical techniques. We aim to present a review of recent
      trends in paediatric BAHD surgery and also discuss alternative treatment options
      available. METHODS: All papers referring to paediatric BAHD surgery (English
      language) were identified from Medline, Pubmed, Cochrane library and Embase
      search in May 2011. Abstracts were read and relevant papers were obtained.
      RESULTS: BAHDs have evolved over recent years as technology has advanced. New
      bone conduction hearing devices have recently been launched such as the Ponto
      system [OticonTM], Alpha 1 (M) hearing system [Sophono], Soundbite system
      [Sonitus] and the Vibrant Soundbridge system [Medel]. Modifications to existing
      implant systems have significantly altered BAHD practice with earlier loading of
      the sound processor now a positive step forward. CONCLUSIONS: The latest
      generation of percutanous devices have been designed to reduce skin
      complications, promote better osseointegration and earlier loading of the sound
      processor. Alternative devices without a skin-penetrating abutment are now
      available and have shown promising results in the paediatric population.

PMID- 22390905
TI  - Letter to the editor regarding 'The effect of adenotonsillectomy on serum insulin
      like growth factors and the adenoid/nasopharynx ratio in pediatric patients: a
      blind, prospective clinical study'.

PMID- 22390907
TI  - Nursing home deficiency citations for physical restraints and restrictive side
      rails.
AB  - This article examines whether nursing home facility-level characteristics are
      associated with the likelihood of receiving deficiency citations for physical
      restraints, including restrictive side rails. Data from the on-line survey
      certification of automated records were used to calculate odds ratios for
      facility-level characteristics associated with these deficiency citations. Repeat
      records from 2000 to 2007 were combined to produce longitudinal data. The results
      of this study show that restraint/side rail deficiency citations were negatively
      associated with higher staffing levels of registered nurses and licensed
      practical nurses (p <= .001) and higher Medicaid reimbursement rates (p <= .01).
      Citations were positively associated with greater nurse aide staffing (p <= .01)
      and higher quality-of-care deficiency citation percentiles (p <= .001). The
      extent of physical restraint and restrictive side rail misuse within nursing
      homes appears to vary according to various facility characteristics. It is less
      clear how internal processes within a facility bring about these observed
      patterns of variation.

PMID- 22390906
TI  - Joint L1 and total variation regularization for fluorescence molecular
      tomography.
AB  - Fluorescence molecular tomography (FMT) is an imaging modality that exploits the
      specificity of fluorescent biomarkers to enable 3D visualization of molecular
      targets and pathways in vivo in small animals. Owing to the high degree of
      absorption and scattering of light through tissue, the FMT inverse problem is
      inherently ill-conditioned making image reconstruction highly susceptible to the
      effects of noise and numerical errors. Appropriate priors or penalties are needed
      to facilitate reconstruction and to restrict the search space to a specific
      solution set. Typically, fluorescent probes are locally concentrated within
      specific areas of interest (e.g., inside tumors). The commonly used L(2) norm
      penalty generates the minimum energy solution, which tends to be spread out in
      space. Instead, we present here an approach involving a combination of the L(1)
      and total variation norm penalties, the former to suppress spurious background
      signals and enforce sparsity and the latter to preserve local smoothness and
      piecewise constancy in the reconstructed images. We have developed a surrogate
      based optimization method for minimizing the joint penalties. The method was
      validated using both simulated and experimental data obtained from a mouse-shaped
      phantom mimicking tissue optical properties and containing two embedded
      fluorescent sources. Fluorescence data were collected using a 3D FMT setup that
      uses an EMCCD camera for image acquisition and a conical mirror for full-surface
      viewing. A range of performance metrics was utilized to evaluate our simulation
      results and to compare our method with the L(1), L(2) and total variation norm
      penalty-based approaches. The experimental results were assessed using the Dice
      similarity coefficients computed after co-registration with a CT image of the
      phantom.

PMID- 22390908
TI  - Effects of polyunsaturated fatty acids on cocaine-conditioned place preference in
      mice.
AB  - OBJECTIVE: The objective of the present study was to assess whether the
      administration of polyunsaturated fatty acids (PUFAs) would lead to alterations
      in cocaine-conditioned place preference by correlating behavioral data and plasma
      levels of PUFAs. METHODS: Five groups of C57Bl/6J mice received a linseed oil
      supplement or a control solution for 19 days and were conditioned to cocaine.
      RESULTS: PUFAs did not exert a protective effect against cocaine-conditioned
      place-preference behavior, although there were significant differences  in the
      levels of eicosapentaenoic acid (EPA) and linoleic acid among the groups tested.
      Higher doses of PUFAs might be necessary to induce a change in the plasma level
      of EPA in cocaine-conditioned mice. DISCUSSION: PUFAs had no effect on cocaine
      conditioned place preference.

PMID- 22390909
TI  - Cardiovascular risk in relation to functionality of sequence variants in the gene
      coding for the low-density lipoprotein receptor: a study among 29,365 individuals
      tested for 64 specific low-density lipoprotein-receptor sequence variants.
AB  - AIMS: A plethora of mutations in the LDL-receptor gene (LDLR) underlie the
      clinical phenotype of familial hypercholesterolaemia (FH). For the diagnosis of
      FH, it is important, however, to discriminate between pathogenic and non
      pathogenic mutations. The aim of the current study was to assess whether true
      pathogenic mutations were indeed associated with the occurrence of coronary
      artery disease (CAD) when compared with non-functional variants. The latter
      variants should not exhibit such an association with CAD. METHODS AND RESULTS: We
      assessed 29 365 individuals tested the 64 most prevalent LDLR variants. First, we
      determined pathogenicity for each of these sequence variants. Subsequently, a Cox
      proportional hazard model was used to compare event-free survival, defined as the
      period from birth until the first CAD event, between carriers and non-carriers of
      LDLR mutations. Fifty-four sequence variants in the LDLR gene were labelled as
      pathogenic and 10 as non-pathogenic. The 9 912 carriers of a pathogenic LDLR
      mutation had a shorter event-free survival than the 18 393 relatives who did not
      carry that mutation; hazard ratio 3.64 [95% confidence interval (CI): 3.24-4.08;
      P< 0.001]. In contrast, the 355 carriers of a non-pathogenic LDLR variant had
      similar event-free survival as the 705 non-carrying relatives; hazard ratio 1.00
      (95% CI: 0.52-1.94; P= 0.999). CONCLUSION: These findings with respect to
      clinical outcomes substantiate our criteria for functionality of LDLR sequence
      variants. They also confirm the CAD risk associated with FH and underline that
      these criteria can be used to decide whether a specific sequence variant should
      be used in cascade screening.

PMID- 22390910
TI  - Right atrial Merkel cell tumour metastasis characterization using a multimodality
      approach.

PMID- 22390911
TI  - Mechanical dyssynchrony evaluated by tissue Doppler cross-correlation analysis is
      associated with long-term survival in patients after cardiac resynchronization
      therapy.
AB  - AIMS: Pre-implant assessment of longitudinal mechanical dyssynchrony using cross
      correlation analysis (XCA) was tested for association with long-term survival and
      compared with other tissue Doppler imaging (TDI)-derived indices. METHODS AND
      RESULTS: In 131 patients referred for cardiac resynchronization therapy (CRT)
      from two international centres, mechanical dyssynchrony was assessed from TDI
      velocity curves using time-to-peak opposing wall delay (OWD) >=80 ms, Yu index
      >=32 ms, and the maximal activation delay (AD-max) >35 ms. AD-max was calculated
      by XCA of the TDI-derived myocardial acceleration curves. Outcome was a composite
      of all-cause mortality, cardiac transplantation, or implantation of a ventricular
      assist device (left ventricular assist device) and modelled using the Cox
      proportional hazards regression. Follow-up was truncated at 1460 days.
      Dyssynchrony by AD-max was independently associated with improved survival when
      adjusted for QRS > 150 ms and aetiology {hazard ratio (HR) 0.35 [95% confidence
      interval (CI) 0.16-0.77], P = 0.01}. Maximal activation delay performed
      significantly better than Yu index, OWD, and the presence of left bundle branch
      block (P < 0.05, all, for difference between parameters). In subgroup analysis,
      patients without dyssynchrony and QRS between 120 and 150 ms showed a
      particularly poor survival [HR 4.3 (95% CI 1.46-12.59), P < 0.01, compared with
      the group with dyssynchrony and QRS between 120 and 150 ms]. CONCLUSION:
      Mechanical dyssynchrony assessed by AD-max was associated with long-term survival
      after CRT and was significantly better associated compared with other TDI-derived
      indices. Patients without dyssynchrony and QRS between 120 and 150 ms had a
      particularly poor prognosis. These results indicate a valuable role for XCA in
      selection of CRT candidates.

PMID- 22390912
TI  - Persistent left superior vena cava draining into the left atrium: an elderly man
      with hypoxia, cyanosis, and paradoxical shunting post-myocardial infarction.

PMID- 22390913
TI  - Prognostic value of coronary vessel dominance in relation to significant coronary
      artery disease determined with non-invasive computed tomography coronary
      angiography.
AB  - AIMS: Limited information is available regarding the relationship between
      coronary vessel dominance and prognosis. Therefore, the purpose of this study was
      to determine the prognostic value of coronary vessel dominance in relation to
      significant coronary artery disease (CAD) in patients referred for computed
      tomography coronary angiography (CTA). METHODS AND RESULTS: The study population
      consisted of 1425 patients (869 men, 57 +/- 12 years) referred for CTA. To
      evaluate the impact of vessel dominance and significant CAD on CTA on outcome,
      patients were followed during a median period of 24 months for the occurrence of
      non-fatal myocardial infarction and all-cause mortality. The presence of a left
      dominant system was identified as a significant predictor for non-fatal
      myocardial infarction and all-cause mortality (HR: 3.20; 95% CI: 1.67-6.13, P <
      0.001) and had incremental value over baseline risk factors and severity of CAD
      on CTA. In addition, in the subgroup of patients with significant CAD on CTA,
      patients with a left dominant system had a worse outcome compared with patients
      with a right dominant system (cumulative event rates: 9.5% and 35% at 3-year
      follow-up for a right and left dominant coronary artery system, respectively, log
      rank P < 0.001). CONCLUSIONS: The presence of a left dominant system was
      identified as an independent predictor of non-fatal myocardial infarction and all
      cause mortality, especially in patients with significant CAD on CTA. Therefore,
      the assessment of coronary vessel dominance on CTA may further enhance risk
      stratification beyond the assessment of significant CAD on CTA.

PMID- 22390914
TI  - MR-IMPACT II: Magnetic Resonance Imaging for Myocardial Perfusion Assessment in
      Coronary artery disease Trial: perfusion-cardiac magnetic resonance vs. single
      photon emission computed tomography for the detection of coronary artery disease:
      a comparative multicentre, multivendor trial.
AB  - AIMS: Perfusion-cardiac magnetic resonance (CMR) has emerged as a potential
      alternative to single-photon emission computed tomography (SPECT) to assess
      myocardial ischaemia non-invasively. The goal was to compare the diagnostic
      performance of perfusion-CMR and SPECT for the detection of coronary artery
      disease (CAD) using conventional X-ray coronary angiography (CXA) as the
      reference standard. METHODS AND RESULTS: In this multivendor trial, 533 patients,
      eligible for CXA or SPECT, were enrolled in 33 centres (USA and Europe) with 515
      patients receiving MR contrast medium. Single-photon emission computed tomography
      and CXA were performed within 4 weeks before or after CMR in all patients. The
      prevalence of CAD in the sample was 49%. Drop-out rates for CMR and SPECT were
      5.6 and 3.7%, respectively (P = 0.21). The primary endpoint was non-inferiority
      of CMR vs. SPECT for both sensitivity and specificity for the detection of CAD.
      Readers were blinded vs. clinical data, CXA, and imaging results. As a secondary
      endpoint, the safety profile of the CMR examination was evaluated. For CMR and
      SPECT, the sensitivity scores were 0.67 and 0.59, respectively, with the lower
      confidence level for the difference of +0.02, indicating superiority of CMR over
      SPECT. The specificity scores for CMR and SPECT were 0.61 and 0.72, respectively
      (lower confidence level for the difference: -0.17), indicating inferiority of CMR
      vs. SPECT. No severe adverse events occurred in the 515 patients. CONCLUSION: In
      this large multicentre, multivendor study, the sensitivity of perfusion-CMR to
      detect CAD was superior to SPECT, while its specificity was inferior to SPECT.
      Cardiac magnetic resonance is a safe alternative to SPECT to detect perfusion
      deficits in CAD.

PMID- 22390915
TI  - Traumatic brain injury: a risk factor for Alzheimer's disease.
AB  - Traumatic brain injury (TBI) constitutes a major global health and socio-economic
      problem with neurobehavioral sequelae contributing to long-term disability. It
      causes brain swelling, axonal injury and hypoxia, disrupts blood brain barrier
      function and increases inflammatory responses, oxidative stress,
      neurodegeneration and leads to cognitive impairment. Epidemiological studies show
      that 30% of patients, who die of TBI, have Abeta plaques which are pathological
      features of Alzheimer's disease (AD). Thus TBI acts as an important epigenetic
      risk factor for AD. This review focuses on AD related genes which are expressed
      during TBI and its relevance to progression of the disease. Such understanding
      will help to diagnose the risk of TBI patients to develop AD and design
      therapeutic interventions.

PMID- 22390916
TI  - First molluscan theta-class Glutathione S-Transferase: identification, cloning,
      characterization and transcriptional analysis post immune challenges.
AB  - Glutathione S-Transferases (GSTs) are multifunctional cytosolic isoenzymes,
      distinctly known as phase II detoxification enzymes. GSTs play a significant role
      in cellular defense against toxicity and have been identified in nearly all
      organisms studied to date, from bacteria to mammals. In this study, we have
      identified a full-length cDNA of the theta class GST from Ruditapes philippinarum
      (RpGSTtheta), an important commercial edible molluscan species. RpGSTtheta was
      cloned and the recombinant protein expressed, in order to study its biochemical
      characteristics and determine its physiological activities. The cDNA comprised an
      ORF of 693 bp, encoding 231 amino acids with a predicted molecular mass of 27 kDa
      and an isoelectric point of 8.2. Sequence analysis revealed that RpGSTtheta
      possessed characteristic conserved domains of the GST_N family, Class Theta
      subfamily (PSSM: cd03050) and GST_C_family Super family (PSSM: cl02776).
      Phylogenetic analysis showed that RpGSTtheta evolutionarily linked with other
      theta class homologues. The recombinant protein was expressed in Escherichia coli
      BL21(DE3) cells and the purified enzyme showed high activity with GST substrates
      like CDNB and 4-NBC. Glutathione dependent peroxidase activity of GST,
      investigated with cumene hydroperoxide as substrate affirmed the antioxidant
      property of rRpGSTtheta. By quantitative PCR, RpGSTtheta was found to be
      ubiquitously expressed in all tissues examined, with the highest levels occurring
      in gills, mantle, and hemocytes. Since GSTs may act as detoxification enzymes to
      mediate immune defense, the effects of pathogen associated molecular pattern,
      lipopolysaccharide and intact Vibrio tapetis bacteria challenge on RpGSTtheta
      gene transcription were studied. Furthermore, the RpGSTtheta expression changes
      induced by immune challenges were similar to those of the antioxidant defense
      enzyme manganese superoxide dismutase (RpMnSOD). To our knowledge, RpGSTtheta is
      the first molluscan theta class GST reported, and its immune-related role in
      Manila clam may provide insights into potential therapeutic targets for
      protecting this important aquaculture species.

PMID- 22390917
TI  - Acute phase protein concentrations after limited distance and long distance
      endurance rides in horses.
AB  - Acute phase proteins (APP) have been described as useful for assessing health in
      human and animal patients, as they closely reflect the acute phase reaction
      (APR). In humans and dogs a reaction analogous to APR has also been described
      after prolonged or strenuous exercise. The aim of this study was to determine, if
      similar reactions occur in endurance horses after limited and long distance
      rides. Seventeen horses that successfully completed various distance competitions
      were tested. Routine haematological and biochemical tests were performed and the
      concentrations of serum amyloid A (SAA), C-reactive protein (CRP) and haptoglobin
      were measured. Typical endurance exercise-induced haematological and biochemical
      changes were observed in all horses, regardless the distance. After long distance
      rides, the level of SAA markedly increased, but CRP and haptoglobin
      concentrations remained unchanged. After limited distance rides no changes in the
      levels of APPs were noted. Exercise-induced APR in horses occurred only after
      prolonged, strenuous exertion, and differed from APR in inflammation in that only
      SAA concentration was increased.

PMID- 22390918
TI  - Re-building life after ICU: a qualitative study of the patients' perspective.
AB  - OBJECTIVE: To explore former ICU patients' views on what the key components of a
      post ICU rehabilitation programme should be. RESEARCH METHODOLOGY: Thirty five
      participants completed an online questionnaire accessed via a link to the study
      from two support groups' websites. Adults (>18 years) who had been patients in
      ICU were invited to take part. Participants were asked open questions about their
      ICU experience and their views on ICU rehabilitation. Participants were: aged
      from 22 to 70 years; from the USA (22), the UK (8), Canada (2), Australia (1) and
      other (2); 30 female and five male. Findings were analysed using a thematic
      approach. FINDINGS: Three themes were identified: 'Information and education',
      'Personal support' and 'Assessment and therapy'. Analysis suggested that for
      participants the aspects of rehabilitation covered by each of the themes were of
      equal importance. CONCLUSION: Healthcare professionals in ICU, acute ward and
      community settings need to be aware of the broad array of physical and
      psychological challenges faced by patients who have been critically ill.
      Healthcare professionals need to ensure a holistic approach is implemented to
      coordinate and facilitate rehabilitation, to address identified patients' needs.

PMID- 22390919
TI  - Measurement of physiologic responses to mobilisation in critically ill adults.
AB  - OBJECTIVE: To identify physiologic variables that could be measured in response
      to mobilisation interventions in critically ill adults. BACKGROUND: Physical
      activity may mitigate muscle damage from critical illness, but critically ill
      patients may have limited activity tolerance. Physiologic measures may be most
      useful in identifying safety and efficacy of mobilisation in this population.
      METHODS: A comprehensive literature search of electronic databases was conducted
      from 1990 to present, including CINAHL, MEDLINE the Cochrane Database of
      Systematic Reviews and PubMed. Search terms used were mobilisation, exercise,
      activity and critical illness. Seventeen articles were identified for review.
      Physiologic measurement approaches were reviewed for precision and accuracy.
      RESULTS: Cardiopulmonary measures comprised the majority of physiologic variables
      identified, and multiple measures were used. Physiologic measures were primarily
      used as indicators of safety, although several efficacy measures were identified.
      Only one standardised tool was found that could be suitable as a safety measure,
      the Borg Rating of Perceived Exertion. The Medical Research Council Muscle
      Strength Grading Scale could be used as a physiologic outcome measure.
      Inflammatory biomarkers may be used as a novel measure of physiologic response.
      Descriptions of approaches to assure precision and accuracy of physiologic
      response measures were extremely limited. CONCLUSIONS: Multiple physiologic
      variables should be measured when considering response to mobilisation in
      critically ill patients. Attention should be paid to procedures to assure
      accuracy and precision in measurement. Future studies including physiologic
      measures should include inflammatory biomarkers, and other measures of
      physiologic function, such as pain assessment.

PMID- 22390920
TI  - Point: Parametrial irradiation in locally advanced cervix cancer can be achieved
      effectively with a variety of external beam techniques.

PMID- 22390921
TI  - Counterpoint: Time to retire the parametrial boost.

PMID- 22390925
TI  - 'Choice': what we mean by it, and what that means for preventing childhood
      obesity.
AB  - OBJECTIVE: (i) To map how US adults value 'choice' in the context of obesity
      policy and (ii) to discuss implications for obesity prevention in children.
      DESIGN: Semi-structured interviews (n =105) were conducted between 2006 and 2009
      about causes of and solutions to childhood obesity. Quotes captured in field
      notes from community meetings (n = 6) on childhood obesity prevention were also
      analysed. Each use of the word 'choice' and its variants was identified in these
      texts. Content and discourse were analysed to identify the implied values and
      meaning in each use. SETTING: North-eastern USA. SUBJECTS: One hundred and five
      adults, some involved in childhood obesity prevention initiatives. RESULTS: Three
      distinct frames of 'choice' emerged: (i) having choices (choice as freedom), (ii)
      making choices (choice as responsibility) and (iii) influencing choices
      (contextual constraints and impacts on choice). Many speakers used more than one
      frame over the course of an interview. Most people using the third frame seemed
      to share the values behind the first two frames, but focused on conditions
      required to enable people to be accountable for their choices and to make truly
      free choices. A small subset thought outside the frame of individual choice,
      valuing, as one person put it, a 'social contract'. CONCLUSIONS: Public debate in
      the USA about responsibility for and solutions to rising obesity rates often
      hinges on notions of 'choice'. These frames, and the values underlying them, are
      not mutually exclusive. Respecting the values behind each 'choice' frame when
      crafting obesity prevention policy and employing all three in public
      communications about such policy may facilitate greater consensus on prevention
      measures.

PMID- 22390924
TI  - Is interleukin-10 gene polymorphism a predictive marker in HCV infection?
AB  - The clinical outcome of hepatitis C virus (HCV) infection varies between
      individuals - from spontaneous viral clearance and persistence without
      complication, to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Also
      patterns of response to interferon-based anti-HCV therapy are different from
      person to person. This diversity may be affected by host genetic factors,
      including alterations in genes encoding cytokines. Interleukin-10, as an anti
      inflammatory cytokine and immune response modulator, may influence on HCV
      infection susceptibility as well as spontaneous and treatment-induced HCV
      eradication. Moreover, it is stated that IL-10 has antifibrotic properties and
      play a role in progression of liver disease. This review summarized studies on
      interleukin-10 gene polymorphisms (mainly promoter SNPs at positions -1082(G/A), 
      819(C/T) and -592(C/A)), which may determine IL-10 production, regarding
      susceptibility to HCV infection, course of HCV-related liver disease (fibrosis,
      cirrhosis, hepatocellular carcinoma, ALT abnormalities), spontaneous viral
      elimination as well as hepatitis C treatment outcomes. Analysis of hereby
      summarized studies shows that it is difficult to unambiguously determine the
      importance of IL-10 polymorphism as a predictor of clinical outcome of hepatitis
      C and response to anti-HCV therapy before its beginning. Thus, future larger
      studies need to address these issues. Continuation of studies on interleukin-10
      polymorphisms as well as identification of other candidate predictive markers in
      HCV infection has important practical implications and there is a chance that may
      contribute to reduce the scale of hepatitis C problem.

PMID- 22390927
TI  - Mechanical loading prevents the stimulating effect of IL-1beta on osteocyte
      modulated osteoclastogenesis.
AB  - Inflammatory diseases such as rheumatoid arthritis are often accompanied by
      higher plasma and synovial fluid levels of interleukin-1beta (IL-1beta), and by
      increased bone resorption. Since osteocytes are known to regulate bone resorption
      in response to changes in mechanical stimuli, we investigated whether IL-1beta
      affects osteocyte-modulated osteoclastogenesis in the presence or absence of
      mechanical loading of osteocytes. MLO-Y4 osteocytes were pre-incubated with IL
      1beta (0.1-1 ng/ml) for 24h. Cells were either or not subjected to mechanical
      loading by 1h pulsating fluid flow (PFF; 0.7 +/- 0.3 Pa, 5 Hz) in the presence of
      IL-1beta (0.1-1 ng/ml). Conditioned medium was collected after 1h PFF or static
      cultures. Subsequently mouse bone marrow cells were seeded on top of the IL-1beta
      treated osteocytes to determine osteoclastogenesis. Conditioned medium from
      mechanically loaded or static IL-1beta-treated osteocytes was added to co
      cultures of untreated osteocytes and mouse bone marrow cells. Gene expression of
      cysteine-rich protein 61 (CYR61/CCN1), receptor activator of nuclear factor kappa
      B ligand (RANKL), and osteoprotegerin (OPG) by osteocytes was determined
      immediately after PFF. Incubation of osteocytes with IL-1beta, as well as
      conditioned medium from static IL-1beta-treated osteocytes increased the
      formation of osteoclasts. However, conditioned medium from mechanically loaded IL
      1beta-treated osteocytes prevented osteoclast formation. Incubation with IL-1beta
      upregulated RANKL and downregulated OPG gene expression by static osteocytes. PFF
      upregulated CYR61, RANKL, and OPG gene expression by osteocytes. Our results
      suggest that IL-1beta increases osteocyte-modulated osteoclastogenesis, and that
      mechanical loading of osteocytes may abolish IL-1beta-induced osteoclastogenesis.

PMID- 22390926
TI  - Targeting Werner syndrome protein sensitizes U-2 OS osteosarcoma cells to
      selenium-induced DNA damage response and necrotic death.
AB  - Mutations in the Werner syndrome protein (WRN), a caretaker of the genome, result
      in Werner syndrome, which is characterized by premature aging phenotypes and
      cancer predisposition. Methylseleninic acid (MSeA) can activate DNA damage
      responses and is a superior compound to suppress tumorigenesis in mouse models of
      cancer. To test the hypothesis that targeting WRN can potentiate selenium
      toxicity in cancer cells, isogenic WRN small hairpin RNA (shRNA) and control
      shRNA U-2 OS osteosarcoma cells were treated with MSeA for 2d, followed by
      recovery for up to 7d. WRN deficiency sensitized U-2 OS cells to MSeA-induced
      necrotic death. Co-treatment with the ataxia-telangiectasia mutated (ATM) kinase
      inhibitor KU55933 desensitized the control shRNA cells, but not WRN shRNA cells,
      to MSeA treatment. WRN did not affect MSeA-induced ATM phosphorylation on Ser
      1981 or H2A.X phosphorylation on Ser-139, but promoted recovery from the MSeA
      induced DNA damage. Taken together, WRN protects U-2 OS osteosarcoma cells
      against MSeA-induced cytotoxicity, suggesting that oxidative DNA repair pathway
      is a promising target for improving the efficacy of selenium on tumor
      suppression.

PMID- 22390928
TI  - ParaAT: a parallel tool for constructing multiple protein-coding DNA alignments.
AB  - Constructing multiple homologous alignments for protein-coding DNA sequences is
      crucial for a variety of bioinformatic analyses but remains computationally
      challenging. With the growing amount of sequence data available and the ongoing
      efforts largely dependent on protein-coding DNA alignments, there is an
      increasing demand for a tool that can process a large number of homologous groups
      and generate multiple protein-coding DNA alignments. Here we present a parallel
      tool - ParaAT that is capable of parallelly constructing multiple protein-coding
      DNA alignments for a large number of homologs. As testified on empirical
      datasets, ParaAT is well suited for large-scale data analysis in the high
      throughput era, providing good scalability and exhibiting high parallel
      efficiency for computationally demanding tasks. ParaAT is freely available for
      academic use only at http://cbb.big.ac.cn/software.

PMID- 22390929
TI  - Exendin-4 restores glucolipotoxicity-induced gene expression in human coronary
      artery endothelial cells.
AB  - Exendin-4, a stable GLP-1 receptor agonist, has been shown to stimulate insulin
      secretion. It has also been shown to exert beneficial effects on endothelial
      function that are independent of its glycemic effects. The molecular mechanisms
      underlying the protective actions of exendin-4 against diabetic glucolipotoxicity
      in endothelial cells largely remain elusive. We have investigated the long-term
      in vitro effect of palmitate or high glucose (simulating the diabetic milieu) and
      the role of exendin-4 on gene expression in human coronary artery endothelial
      cells. Gene expression profiling in combination with Western blotting revealed
      that exendin-4 regulates expression of a number of genes involved in
      angiogenesis, inflammation and thrombogenesis under glucolipotoxic conditions.
      Our results indicate that exendin-4 may improve endothelial cell function in
      diabetes through regulating expression of the genes, whose expression was
      disrupted by glucolipotoxicity. As endothelial dysfunction appears to be an early
      indicator of vascular damage, and predicts both progression of atherosclerosis
      and incidence of cardiovascular events, exendin-4 and possibly other incretin
      based strategies may confer additional cardiovascular benefit beyond improved
      glycemic control.

PMID- 22390930
TI  - AQP9: a novel target for bone loss induced by microgravity.
AB  - The aim of current study was to elucidate whether aquaporin-9 (AQP9) expression
      was involved in the progression of bone loss induced by microgravity. We used the
      hind-limb suspension (HLS) mice model to simulate microgravity and induce bone
      loss. It was found that HLS exposure decreased femur bone mineral density (BMD),
      and enhanced femur AQP9 mRNA and protein levels. Then, the relationship between
      AQP9 mRNA expression and BMD was studied and it was showed that femur AQP9 mRNA
      level was negatively related to femur BMD in mice exposed to HLS. We sought to
      exam the function of AQP9 in the femur using the AQP9-null mice. It was found
      that AQP9 knockout attenuated bone loss and inhibited osteoclastogenesis under
      the condition of HLS exposure, but had no similar effect on bone under normal
      physiological conditions. In addition, it was found that exposure to simulated
      hypergravity or exercise training, main countermeasures against microgravity,
      reduced AQP9 mRNA and protein levels in femur of mice. Moreover, it was found
      that both aging and estrogen deprivation, another two risk factors of bone loss,
      had no significant effect on femur AQP9 expression. In conclusion, AQP9 plays an
      important role in the development of microgravity-induced bone loss, and may be a
      potential target for the prevention or management of microgravity-induced bone
      loss.

PMID- 22390931
TI  - Expression and prognostic relevance of PRAME in primary osteosarcoma.
AB  - The preferentially expressed antigen of melanoma (PRAME), a cancer-testis antigen
      with unknown function, is expressed in many human malignancies and is considered
      an attractive potential target for tumor immunotherapy. However, studies of its
      expression and function in osteosarcoma have rarely been reported. In this study,
      we found that PRAME is expressed in five osteosarcoma cell lines and in more than
      70% of osteosarcoma patient specimens. In addition, an immunohistochemical
      analysis showed that high PRAME expression was associated with poor prognosis and
      lung metastasis. Furthermore, PRAME siRNA knockdown significantly suppressed the
      proliferation, colony formation, and G1 cell cycle arrest in U-2OS cells. Our
      results suggest that PRAME plays an important role in cell proliferation and
      disease progression in osteosarcoma. However, the detail mechanisms of PRAME
      function in osteosarcoma require further investigation.

PMID- 22390932
TI  - Possible involvement of melanocortin-4-receptor and AMP-activated protein kinase
      in the interaction of glucagon-like peptide-1 and leptin on feeding in rats.
AB  - Glucagon-like peptide-1 (GLP-1) and leptin are anorectic hormones produced in the
      small intestine and white adipose tissue, respectively. Investigating how these
      hormones act together as an integrated anorectic signal is important to elucidate
      a mechanism to maintain energy balance. In the present study, coadministration of
      subthreshold GLP-1 and leptin dramatically reduced feeding in rats. Although
      coadministration of GLP-1 with leptin did not enhance leptin signal transduction
      in the hypothalamus, it significantly decreased phosphorylation of AMP-activated
      protein kinase (AMPK). In addition, coadministration of GLP-1 with leptin
      significantly increased proopiomelanocortin (POMC) mRNA levels. Considering that
      alpha-melanocortin stimulating hormone (alpha-MSH) is derived from POMC and
      functions through the melanocortin-4-receptor (MC4-R) as a key molecule involved
      in feeding reduction, the interaction of GLP-1 and leptin on feeding reduction
      may be mediated through the alpha-MSH/MC4-R system. As expected, the interaction
      of GLP-1 and leptin was abolished by intracerebroventricular preadministration of
      the MC4-R antagonists agouti-related peptide and SHU9119. Taken together, GLP-1
      and leptin cooperatively reduce feeding at least in part via inhibition of AMPK
      following binding of alpha-MSH to MC4-R.

PMID- 22390933
TI  - An involvement of SR-B1 mediated PI3K-Akt-eNOS signaling in HDL-induced
      cyclooxygenase 2 expression and prostacyclin production in endothelial cells.
AB  - It is well-known that sphingosine-1-phosphate (S1P), the phospholipid content of
      HDL, binding to S1P receptors can raise COX-2 expression and PGI(2) release
      through p38MAPK/CREB pathway. In the present study we assess the action of SR-B1
      initiated PI3K-Akt-eNOS signaling in the regulation of COX-2 expression and
      PGI(2) production in response to HDL. We found that apoA1 could increase PGI(2)
      release and COX-2 expression in ECV 304 endothelial cells. Furthermore, SR-B1 was
      found to be involved in HDL induced up-regulation of COX-2 and PGI(2). Over
      expressed SR-B1 did not significantly increase the expression of COX-2 and the
      PGI(2) levels, but knock-down of SR-B1 by siRNA could significantly attenuate COX
      2 expression and PGI(2) release together with p38MAPK and CREB phosphorylation.
      Consistently, the declines of p-p38MAPK, p-CREB, COX-2 and PGI(2) were also
      observed after incubation with LY294002 (25MUmol/L; PI3K special inhibitor) or L
      NAME (50MUmol/L; eNOS special inhibitor). In addition, we demonstrated the
      increases of PGI(2) release, COX-2 expression and p38MAPK phosphorylation, when
      nitric oxide level was raised through the incubation of L-arginine (10 or
      20nmol/L) in endothelial cells. Taking together, our data support that SR-B1
      mediated PI3K-Akt-eNOS signaling was involved in HDL-induced COX-2 expression and
      PGI(2) release in endothelial cells.

PMID- 22390934
TI  - High circulating levels of S100A8/A9 complex (calprotectin) in male Japanese with
      abdominal adiposity and dysregulated expression of S100A8 and S100A9 in adipose
      tissues of obese mice.
AB  - S100A8/A9 complex, calprotectin, which serves as an endogenous ligand for immune
      pathways, is associated with atherosclerosis. These proteins are reported to have
      several functions such as activating NADPH oxidase, binding toll-like receptor 4
      and associated with the receptor for advanced glycation end-products. We recently
      reported S100A8 mRNA was highly expressed in mouse white adipose tissues and
      differentiated 3T3-L1 adipocytes. However, regulation of S100A9 expression in
      murine adipose tissue remains to be elucidated. The results of our studies in
      male Japanese, obese and control mice and cultured cells showed: (1) serum levels
      of S100A8/A9 complex, calprotectin, correlated with visceral fat area, body mass
      index, subcutaneous fat area, and leukocyte count in 500 Japanese men, and (2)
      higher mRNA expression levels of S100A8 in mature adipocyte fraction and S100A9
      in stromal vascular cell fraction of obese mice, compared with those of lean
      mice. Overexpression of S100A8 and S100A9 in obese adipose tissue may be
      involved, at least partly, in not only high circulating levels of S100A8/A9
      complex in abdominal obesity but also adipose and systemic tissue inflammation.

PMID- 22390935
TI  - Proprotein convertases in post-menopausal endometrial cancer: distinctive
      regulation and non-invasive diagnosis.
AB  - Proprotein convertases (PCs) play critical roles in cleaving precursor proteins
      (growth factors, hormones, receptors and adhesion molecules) for activation. PCs
      are implicated in a number of cellular functions, including oncogenesis.
      Endometrial cancer is the most common gynecological cancer in the developed
      world, but the involvement of PCs is unclear. To characterize the role of PCs in
      endometrial cancer, we assessed expression of seven PCs (PC1/3, PC2, PACE4, PC4,
      furin, PC5/6 and PC7) by RT-PCR in six well characterized endometrial cancer cell
      lines. Expression was variable in all lines, with furin being most consistently
      expressed in all cell lines tested. We next determined the cellular localization
      and expression levels of four ubiquitously expressed PCs (furin, PACE4, PC5/6 and
      PC7) in post-menopausal endometrial biopsies from control (n=7) and endometrial
      cancer patients (n=30) by immunohistochemistry. Furin increased in tumors,
      whereas PC5/6, PACE4 and PC7 expression was reduced with increasing cancer
      grades. Uterine lavage is a non-invasive source material for evaluating the
      endometrium. We thus assessed whether total PC activity was altered in uterine
      lavage of endometrial cancer patients (n=36) compared to controls (n=10). PC
      activity was detected in all uterine lavage samples, and significantly elevated
      in all grades of endometrial cancer. This study demonstrates a complex
      association between individual PCs and endometrial cancer. Importantly, we show
      that monitoring the total PC activity in uterine lavage may provide a rapid and
      non-invasive method for the diagnosis of endometrial cancer in postmenopausal
      women.

PMID- 22390937
TI  - Current applications of oogram methodology in experimental schistosomiasis;
      fecundity of female Schistosoma mansoni and egg release in the intestine of AKR/J
      mice following immunomodulatory treatment with pentoxifylline.
AB  - Oogram methodology permitted a direct assessment of the fecundity of Schistosoma
      mansoni and the passage of parasite eggs from mesenteric vessels into the
      intestinal lumen in AKR/J mice that had been infected via the intraperitoneal
      route with 60 cercariae of the trematode and later subjected to short-term
      subcutaneous treatments with pentoxifylline (PTX). The administration of PTX did
      not change oviposition kinetics, the individual fecundity of female parasites (as
      determined by the study of the ratio of second-stage S. mansoni eggs per g
      intestine/number of female parasites recovered from the portal system), nor the
      number of mature and dead eggs retained in the host tissue, though the drug has
      known immunomodulatory effects, as shown previously in experimental
      schistosomiasis. A better appraisal was also carried out, including the study of
      statistical parameters, concerning the utilization of the ratios of each stage of
      immature eggs (first to fourth) per g intestine/number of female worms from the
      portal system. The second-stage eggs had the lowest variability, confirming that
      the utilization of this stage as an indicator of the individual fecundity of
      parasite females is indeed viable. In the light of our findings, current uses of
      oogram methodology are discussed. Moreover, additional consideration is given to
      data obtained in the present study concerning intraperitoneal infection with S.
      mansoni cercariae in both untreated and treated mice of the AKR/J strain, such as
      the recovery of mature worms, eggs and free granulomas from the peritoneal cavity
      of these rodents.

PMID- 22390936
TI  - Cyclin-dependent kinase inhibitor 3 is overexpressed in hepatocellular carcinoma
      and promotes tumor cell proliferation.
AB  - Cyclin-dependent kinase inhibitor 3 (CDKN3) belongs to the protein phosphatases
      family and has a dual function in cell cycling. The function of this gene has
      been studied in several kinds of cancers, but its role in human hepatocellular
      carcinoma (HCC) remains to be elucidated. In this study, we found that CDKN3 was
      frequently overexpressed in both HCC cell lines and clinical samples, and this
      overexpression was correlated with poor tumor differentiation and advanced tumor
      stage. Functional studies showed that overexpression of CDKN3 could promote cell
      proliferation by stimulating G1-S transition but has no impact on cell apoptosis
      and invasion. Microarray-based co-expression analysis identified a total of 61
      genes co-expressed with CDKN3, with most of them involved in cell proliferation,
      and BIRC5 was located at the center of CDKN3 co-expression network. These results
      suggest that CDKN3 acts as an oncogene in human hepatocellular carcinoma and
      antagonism of CDKN3 may be of interest for the treatment of HCC.

PMID- 22390938
TI  - WHIDE--a web tool for visual data mining colocation patterns in multivariate
      bioimages.
AB  - MOTIVATION: Bioimaging techniques rapidly develop toward higher resolution and
      dimension. The increase in dimension is achieved by different techniques such as
      multitag fluorescence imaging, Matrix Assisted Laser Desorption / Ionization
      (MALDI) imaging or Raman imaging, which record for each pixel an N-dimensional
      intensity array, representing local abundances of molecules, residues or
      interaction patterns. The analysis of such multivariate bioimages (MBIs) calls
      for new approaches to support users in the analysis of both feature domains:
      space (i.e. sample morphology) and molecular colocation or interaction. In this
      article, we present our approach WHIDE (Web-based Hyperbolic Image Data Explorer)
      that combines principles from computational learning, dimension reduction and
      visualization in a free web application. RESULTS: We applied WHIDE to a set of
      MBI recorded using the multitag fluorescence imaging Toponome Imaging System. The
      MBI show field of view in tissue sections from a colon cancer study and we
      compare tissue from normal/healthy colon with tissue classified as tumor. Our
      results show, that WHIDE efficiently reduces the complexity of the data by
      mapping each of the pixels to a cluster, referred to as Molecular Co-Expression
      Phenotypes and provides a structural basis for a sophisticated multimodal
      visualization, which combines topology preserving pseudocoloring with information
      visualization. The wide range of WHIDE's applicability is demonstrated with
      examples from toponome imaging, high content screens and MALDI imaging (shown in
      the Supplementary Material). AVAILABILITY AND IMPLEMENTATION: The WHIDE tool can
      be accessed via the BioIMAX website http://ani.cebitec.uni-bielefeld.de/BioIMAX/;
      Login: whidetestuser; Password: whidetest.

PMID- 22390939
TI  - Combining multiple approaches for gene microarray classification.
AB  - MOTIVATION: The microarray report measures the expressions of tens of thousands
      of genes, producing a feature vector that is high in dimensionality and that
      contains much irrelevant information. This dimensionality degrades classification
      performance. Moreover, datasets typically contain few samples for training,
      leading to the 'curse of dimensionality' problem. It is essential, therefore, to
      find good methods for reducing the size of the feature set. RESULTS: In this
      article, we propose a method for gene microarray classification that combines
      different feature reduction approaches for improving classification performance.
      Using a support vector machine (SVM) as our classifier, we examine an SVM trained
      using a set of selected genes; an SVM trained using the feature set obtained by
      Neighborhood Preserving Embedding feature transform; a set of SVMs trained using
      a set of orthogonal wavelet coefficients of different wavelet mothers; a set of
      SVMs trained using texture descriptors extracted from the microarray, considering
      it as an image; and an ensemble that combines the best feature extraction methods
      listed above. The positive results reported offer confirmation that combining
      different features extraction methods greatly enhances system performance. The
      experiments were performed using several different datasets, and our results
      [expressed as both accuracy and area under the receiver operating characteristic
      (ROC) curve] show the goodness of the proposed approach with respect to the state
      of the art. AVAILABILITY: The MATHLAB code of the proposed approach is publicly
      available at bias.csr.unibo.it/nanni/micro.rar.

PMID- 22390940
TI  - CentiLib: comprehensive analysis and exploration of network centralities.
AB  - CentiLib is a library and plug-in for the comprehensive analysis and exploration
      of network centralities. It provides 17 different node centrality and four graph
      centrality measures in a user-friendly interface and supports the exploration of
      analysis results within the networks. Its architecture allows for easy adaption
      to Java-based network analysis, simulation and visualization tools, which is
      demonstrated by providing the plug-in for two popular network analysis tools
      Cytoscape and Vanted. With the ability to quantitatively analyze biological
      networks in an interactive and visual manner, CentiLib supports a better
      understanding of complex biological networks and processes. AVAILABILITY AND
      IMPLEMENTATION: Software with manual and tutorials is freely available at
      http://centilib.ipk-gatersleben.de/.

PMID- 22390941
TI  - Low predictability of anthropometric indicators of obesity in metabolic syndrome
      (MS) risks among elderly women.
AB  - While diagnostic criteria for MS may vary depending on ethnicity, obesity remains
      a key risk factor in its development. In Taiwan, the incidence of obesity and MS
      among women has been increasing; however cut-off values for defining obesity for
      the diagnosis of MS among different groups of women have not been clearly
      established. The goal of this research was to examine the suitability of various
      anthropometric indicators of obesity in predicting the presence of MS criteria
      and to determine appropriate cut-off values of these indicators for women of
      different age and menstrual status. The sample was derived from the 2002 "Taiwan
      Three High Prevalence Survey" database. Women were divided into three groups
      based on age and menstrual status. Receiver-operating characteristic (ROC) curves
      was applied to the anthropometric indicators of obesity including, body mass
      index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height
      ratio (WHtR), to ascertain its value in predicting MS. 2848 cases were included.
      It was found that most MS component values were worse with age and following
      menopause. Obesity indicators showed poor predictability for MS risks in post
      menopausal women over 65 years, but good predictability in women under 65 years;
      our study revealed the following as ideal cut-off values for non-menopausal
      female: WHtR<0.49, WC<78 cm, WHR<0.79, BMI<24 kg/m(2); for menopausal women,
      WHtR<0.54, WC<83 cm, WHR<0.84, BMI<24.4 kg/m(2). It was concluded that obesity
      alone is not a reliable predictor of MS risks in women over the age of 65, and
      cut-off values for obesity indicators need to be further reduced in non
      menopausal women.

PMID- 22390942
TI  - Functional interactions between the paraventricular hypothalamic nucleus and
      raphe magnus. A comparative study of an integrated homeostatic analgesic
      mechanism.
AB  - This work compares the effects of electrical stimulation of the paraventricular
      hypothalamic nucleus (PVN) and the raphe magnus nucleus (RMg) on the single-unit
      response from dorsal spinal cord neurons activated by nociceptive receptive field
      stimulation. We evaluated the effects of stimulating the PVN or RMg individually
      or simultaneously, as well as PVN stimulation after RMg electrolytic lesion. PVN
      or RMg stimulation suppressed the A-delta, C fiber, and postdischarge, and we
      demonstrated that their simultaneous stimulation increases the duration and
      intensity of suppressive effects. RMg lesion increased the peripheral responses,
      but PVN stimulation continued to be suppressive. The intrathecal administration
      of 20 MUl of a 10-5 M solution of a specific oxytocin antagonist strongly reduced
      the PVN effects, and 20 MUl of 10-6 M naloxone significantly reduced the RMg
      suppression of receptive field responses. Some spinal cord cells presented a
      short-latency, evoked action potential (6.8 ms and a variability of +/-0.5 ms)
      produced by the RMg stimulation. This is interpreted as a direct postsynaptic
      action of the RMg on the spinal cord cells. We never found similar responses
      produced by the PVN, and therefore, we propose that the PVN effects are
      presynaptic. Finally, the immunohistochemical experiments confirmed the
      oxytocinergic and the vasopresinergic innervation used by the PVN projection to
      the RMg, and they raise the possibility that other neurotransmitters are
      involved. We conclude that the PVN and the RMg form part of a homeostatic
      analgesic mechanism acting on the same spinal cord cells to block the noxious
      information, but using different mechanisms. Both structures, and others,
      contribute to the homeostatic mechanism of endogenous analgesia.

PMID- 22390943
TI  - Haloperidol and clozapine block formation of autophagolysosomes in rat primary
      neurons.
AB  - Early intervention and maintenance treatment for schizophrenia patients may
      prolong the duration of exposure to antipsychotic agents; however, there have
      been few studies on the neurotoxicity of these agents. Here, we investigated the
      effects of antipsychotics on cell viability and autophagy in rat primary neurons.
      Cultured cortical neurons obtained from rat embryos were treated with various
      concentrations of haloperidol and clozapine, and the neuronal toxicity was
      assessed by measuring lactate dehydrogenase (LDH) activity and 3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
      (MTS) assay. Autophagosomes were quantitated by measuring the level of
      microtubule-associated protein 1A/1B-light chain 3 (LC3-II) by Western blot and
      immunofluorescence staining. Autophagic flux was assayed using bafilomycin A1 and
      GFP-mCherry-LC3 transfection. Haloperidol and clozapine decreased the viability
      of neurons in vitro in a concentration- and time-dependent manner. We also
      observed increased accumulation of autophagosomes after antipsychotic treatment.
      Using bafilomycin A1 and GFP-mCherry-LC3 transfection, we discovered that
      haloperidol and clozapine inhibited autophagosome turnover resulting in a
      dysfunctional autophagic process, including impaired lysosomal fusion. Together,
      these results suggest that haloperidol and clozapine negatively affect neuronal
      viability, possibly by blocking autophagolysosome formation.

PMID- 22390945
TI  - Importance of root HTO uptake in controlling land-surface tritium dynamics after
      an-acute HT deposition: a numerical experiment.
AB  - To investigate the role of belowground root uptake of tritiated water (HTO) in
      controlling land-surface tritium (T) dynamics, a sophisticated numerical model
      predicting tritium behavior in an atmosphere-vegetation-soil system was
      developed, and numerical experiments were conducted using the model. The
      developed model covered physical tritiated hydrogen (HT) transport in a
      multilayered atmosphere and soil, as well as microbial oxidation of HT to HTO in
      the soil, and it was incorporated into a well-established HTO-transfer
      organically bound tritium (OBT)-formation model. The model performance was tested
      through the simulation of an existing HT-release experiment. Numerical
      experiments involving a hypothetical acute HT exposure to a grassland field with
      a range of rooting depths showed that the HTO release from the leaves to the
      atmosphere, driven by the root uptake of the deposited HTO, can exceed the HTO
      evaporation from the ground surface to the atmosphere when root water absorption
      preferentially occurs beneath the ground surface. Such enhanced soil-leaf
      atmosphere HTO transport, caused by the enhanced root HTO uptake, increased HTO
      concentrations in both the surface atmosphere and in the cellular water of the
      leaf. Consequently, leaf OBT assimilation calculated for shallow rooting depths
      increased by nearly an order of magnitude compared to that for large rooting
      depths.

PMID- 22390944
TI  - Orexinergic modulation of GABAergic neurotransmission to cardiac vagal neurons in
      the brain stem nucleus ambiguus changes during development.
AB  - Cardiac vagal neurons (CVNs) in the nucleus ambiguus (NA) are the major
      determinant of parasympathetic activity to the heart. Spontaneous GABAergic
      neurotransmission to CVNs is modulated by hypothalamic neuropeptide orexin-A in
      postnatal days 2-5 (P5) rats; however, during early postnatal development, orexin
      expression changes, and the role of orexin-A in modulating CVN activity at other
      stages of development is unknown. In this study, we compared changes in GABAergic
      inhibitory postsynaptic currents (IPSCs) in CVNs evoked by orexin-A in P5, P16-20
      (P20), and P27-30 (P30) rats using an in vitro brain stem slice preparation. Bath
      applied orexin-A enhanced GABAergic IPSCs in all CVNs tested in P5 and P30
      animals and in the majority of neurons tested in P20 pups. Focal application of
      orexin-A ejected from a pipette positioned within 30 MUm of the patched CVN did
      not alter GABAergic signaling in P5 pups. In contrast, in both P20 and P30 rats,
      focal application of orexin-A inhibited GABAergic IPSCs, and this inhibition
      persisted in the presence of tetrodotoxin. These results indicate orexin-A
      facilitates GABAergic IPSCs likely by activating preceding GABAergic neurons that
      project to CVNs. Orexin-A also likely acts at GABAergic presynaptic terminals
      surrounding CVNs within the NA to inhibit GABA release. The latter mechanism is
      absent in P5 pups but occurs in P20 and P30 rats. In conclusion, this study
      elucidates an important maturation of the parasympathetic cardiac control system.
      Alterations in these developmental mechanisms may play a role in pathogenesis of
      disorders related to a specific stage of development maturation.

PMID- 22390946
TI  - Impact of 5-HT3 receptor antagonists on peripheral and central diseases.
AB  - In this article we discuss the novel pharmacological aspects of 5-HT(3) receptor
      antagonists. Commonly used to counteract chemotherapy-induced emesis, these
      agents now appear to be reaching out for newer indications. Studies have reported
      neuroprotective and anti-inflammatory properties in vitro and in vivo. 5-HT(3)
      receptor antagonists can modulate the immune-inflammatory axis through blockade
      of 5-HT(3) receptors present on immune cells. We review evidence addressing the
      effects of these drugs on peripheral inflammatory diseases, including asthma,
      rheumatoid diseases, inflammatory bowel disease and sepsis in addition to
      diabetes and CNS disorders, including Alzheimer's disease (AD), seizure and
      stroke.

PMID- 22390948
TI  - Upper-body muscular endurance in female university-level modern dancers: a pilot
      study.
AB  - Physical demands vary among dance styles, and injury patterns differ accordingly.
      Modern dance tends to be high in upper-body demands, and university-level female
      modern dancers are suggested to be at high risk for upper-body injury. Low
      muscular endurance is a known injury risk factor.  Whether modern dancers have
      different upper-body muscular endurance than non-dancers is unclear. Thus, the
      purpose of this study was to compare upper-body endurance in female university
      level modern dancers (n = 17) and physically active non-dancers (n = 15), using
      the modified push-up test.  Pearson-correlations examined relationships between
      anthropometrics and push-ups. Multiple regression analyses were used to determine
      whether anthropometrics and physical activity could predict push-up scores. One
      way ANOVAs compared upper-body endurance (number of push-ups) and physical
      activity  between groups (p < 0.05). Except for height (r = -.37), no variables
      were related to push-ups. Neither anthropometrics nor physical activity were able
      to predict push-up scores (p = 0.25). Despite dancers being more active/day (3.6
      +/- 1.9 vs. 0.9 +/- 0.4 hrs/day, p < 0.001),  more times per week (5.4 +/- 1.2
      vs. 4.0 +/- 1.8, p = 0.02), and having greater overall physical activity volumes
      (20.4 +/- 11.4 vs. 3.3 +/- 2.5 hrs/week, p < 0.001) than non-dancers, both groups
      had similar upper-body endurance (22.2 +/- 8.6 vs. 19.9 +/- 8.2,  p = 0.44). A
      probable explanation for this similarity exists in the lack of physical activity
      beyond dance itself performed by the dancers; our preliminary work suggests that
      modern dance alone may not produce upper-body muscle endurance gains. Hence, it
      is suggested that modern dancers should  engage in strength and conditioning
      training programs to enhance upper-body endurance.

PMID- 22390947
TI  - Analytic regularization for landmark-based image registration.
AB  - Landmark-based registration using radial basis functions (RBF) is an efficient
      and mathematically transparent method for the registration of medical images. To
      ensure invertibility and diffeomorphism of the RBF-based vector field, various
      regularization schemes have been suggested. Here, we report a novel analytic
      method of RBF regularization and demonstrate its power for Gaussian RBF. Our
      analytic formula can be used to obtain a regularized vector field from the
      solution of a system of linear equations, exactly as in traditional RBF, and can
      be generalized to any RBF with infinite support. We statistically validate the
      method on global registration of synthetic and pulmonary images. Furthermore, we
      present several clinical examples of multistage intensity/landmark-based
      registrations, where regularized Gaussian RBF are successful in correcting
      locally misregistered areas resulting from automatic B-spline registration. The
      intended ultimate application of our method is rapid, interactive local
      correction of deformable registration with a small number of mouse clicks.

PMID- 22390949
TI  - Effects of voice enhancement technology and relaxing music on the frequency of
      imagery among break dancers.
AB  - A device was developed in 2008 by Hypnoke International Ltd. for use by
      performance consultants and hypnotherapists. It enhances a practitioner's voice
      and blocks out auditory distractions while delivering imagery inductions, thereby
      increasing their effectiveness. This study examined  the impact of voice
      enhancement technology and relaxing music on the frequency of imagery experienced
      by a sample of elite British break dancers (N = 20; mean age = 26.5 years, SD =
      1.5 years). An imagery script was administered to participants under four
      conditions: voice enhancement with  music, voice enhancement only, a music-only
      control, and a no-voice-enhancement-and-no-music control. Frequency of imagery
      was assessed using the Sport Imagery Questionnaire. There was a higher incidence
      of imagery in the voice enhancement with music, voice enhancement only, and music
      only  conditions when compared to the no-voice-enhancement-and-no-music control.
      The key finding was that imagery was most frequent when voice enhancement was
      combined with music in a complementary manner. Thus, it is concluded that the use
      of voice enhancement technology can improve the efficacy  of relaxation and
      imagery training for break dancers, and potentially, dancers in general.

PMID- 22390950
TI  - Injuries in professional modern dancers: incidence, risk factors, and management.
AB  - Modern (or contemporary) dance has become increasingly popular, yet little has
      been reported with respect to modern dance injuries and their consequences. The
      purpose of this study is to define the incidence, risk factors, and management of
      musculoskeletal injuries in professional modern  dancers. A total of 184 dancers
      in the United States completed an anonymous 17-page questionnaire on their
      injuries, including extensive details regarding the two most severe injuries that
      had occurred in the prior 12 months. According to their self-reports, a total of
      82% of the dancers had  suffered between one and seven injuries. The foot and
      ankle (40%) was the most common site of injury, followed by the lower back (17%)
      and the knee (16%). The rate of injuries was 0.59 per 1,000 hours of class and
      rehearsal. Injured male dancers returned to full dancing after a median of 21 
      days, while females returned after a median of 18 days. Most dancers missed no
      performances due to injury. Of the medical consultations sought by dancers for
      their injuries, 47% were made to physicians, 41% to physical therapists, and 34%
      to chiropractors. The majority of dancers adhered to  the advice given them by
      consultants (87% of males and 78% of females for the most severe injury). While
      the majority of injuries were considered work-related (61% of the most severe
      injury and 69% of the second most severe), few were covered by Workers'
      Compensation insurance (12% and 5%  respectively). These professional modern
      dancers suffer from a rate of injury similar to other groups of professional
      dancers. Most dancers return to a partial level of dancing several weeks before
      attempting full-capacity dancing.

PMID- 22390951
TI  - Differences in segmental coordination and postural control in a multi-joint dance
      movement: developpe arabesque.
AB  - Analysis of skill at multiple points on the learning continuum provides insight
      into how complex limb and postural organization is modified with extended
      practice. Dancers at three skill levels were compared performing a domain
      specific movement (developpe arabesque) to  identify motor control parameters
      underlying skill acquisition of a sequential multi-joint trunk and extremity
      movement. It was hypothesized that general organization would be similar between
      groups, but that segmental coordination and postural control would differ with
      skill level. Twenty-seven  expert, advanced, and intermediate dancers performed
      six repetitions of an arabesque sequence with the right limb. Data were acquired
      with a five-camera motion analysis system. Differences between groups in pelvis
      and gesture limb displacement, joint coordination patterns, and variability  were
      determined using ANOVA with post hoc comparisons where applicable. Subjects
      displayed similar movement organization and timing. Differences were found in
      postural pelvic control and intra- and inter-limb coordination. These differences
      were most apparent during the arabesque phase. Control  of the pelvis appears to
      be a key area that requires prolonged practice to master.

PMID- 22390952
TI  - Effects of kinesthetic versus visual imagery practice on two technical dance
      movements: a pilot study.
AB  - Motor imagery is a type of mental practice that involves imagining the body
      performing a movement in the absence of motor output. Dance training
      traditionally incorporates mental practice techniques, but quantitative effects
      of motor imagery on the performance of dance movements are  largely unknown. This
      pilot study compared the effects of two different imagery modalities, external
      visual imagery and kinesthetic imagery, on pelvis and hip kinematics during two
      technical dance movements, plie and saute. Each of three female dance students
      (mean age = 19.7  years, mean years of training = 10.7) was assigned to use a
      type of imagery practice: visual imagery, kinesthetic imagery, or no imagery.
      Effects of motor imagery on peak external hip rotation varied by both modality
      and task. Kinesthetic imagery increased peak external hip rotation for plies, 
      while visual imagery increased peak external hip rotation for sautes. Findings
      suggest that the success of motor imagery in improving performance may be task
      specific. Dancers may benefit from matching imagery modality to technical tasks
      in order to improve alignment and thereby avoid  chronic injury.

PMID- 22390953
TI  - A kinematic approach to calculating ground reaction forces in dance.
AB  - A technique that can be used with dancers for the calculation of ground reaction
      forces in the absence of force plates is described. The ground reaction forces
      are required for analyzing potentially injurious activity within the dancer's
      body. However, the use of a force plate for this  purpose disrupts the
      performance surface and could, due to its stiffness, in itself lead to injury.
      This technical report provides an indication that a technique utilizing kinematic
      calculations of ground reaction forces in dancers offers a viable alternative.
      The kinematic calculations technique  is suitable for use across large
      performance surfaces, including sprung floors. In this preliminary study, it is
      validated against force plate output using data from a single dancer and is
      extended to consider tuning of the generic mass distribution model to improve
      accuracy in the calculation  of ground reaction forces.

PMID- 22390954
TI  - Chewing gum, occupational stress, work performance and wellbeing. An intervention
      study.
AB  - An intervention study was carried out to examine the effects of chewing gum on
      occupational stress and related outcomes. 101 volunteers from Cardiff University
      completed the study. The results showed that chewing gum reduced stress (both at
      work and outside work), reduced fatigue, reduced anxiety and depression and led
      to a more positive mood. Chewing gum was also associated with perceptions of
      better performance (both at work and outside).

PMID- 22390955
TI  - Evaluation of remedial options for a benzene-contaminated site through a
      simulation-based fuzzy-MCDA approach.
AB  - A simulation-based fuzzy multi-criteria decision analysis (SFMCDA) method is
      developed for supporting the selection of remediation strategies for petroleum
      contaminated sites. SFMCDA integrates process modeling (using BIOPLUME III) and
      fuzzy ranking (based on fuzzy TOPSIS) into a general management framework, and
      can compare various remediation alternatives, in light of both cost-risk
      tradeoffs and uncertainty impacts. The proposed method is applied to a
      hypothetical contaminated site suffering from a benzene leakage problem. Six
      remediation alternatives are taken into consideration, including natural
      attenuation (NA), pump-and-treat (PAT), enhanced natural attenuation (ENA), and a
      number of their combinations. Six fuzzy criteria, including both cost and risk
      information, are used to compare different alternatives through fuzzy TOPSIS. The
      results demonstrates that the proposed method can help systematically analyze
      fuzzy inputs from contaminant transport modeling, cost implications and
      stakeholders' preferences, and provide useful ranking information covering a
      variety of decision-relevant remediation options for decision makers.

PMID- 22390956
TI  - Heavy metals and trace elements in atmospheric fall-out: their relationship with
      topsoil and wheat element composition.
AB  - The objectives of this study were to determine the average concentrations and
      deposition rates of 28 elements in atmospheric bulk deposition and to elucidate
      associations among topsoil, bulk deposition and wheat element composition. The
      fluxes of arsenic (As), copper (Cu), lead (Pb) and zinc (Zn) deposition in
      Cordoba were higher than in other agro-ecosystems, which reflects both natural
      (geochemistry and topsoil removal) and anthropogenic sources. High lanthanide,
      uranium (U) and thorium (Th) concentrations revealed the impact of an open cast
      uranium mine. The highest enrichment factors (EF) were those of Cu, Pb, Zn and
      nickel (Ni), with calcium (Ca) being the most prominent in the surroundings of a
      cement plant. Industries and the transport of airborne urban pollutants were the
      main anthropogenic sources for Ca, Cu, Ni, Pb, Zn, cadmium (Cd), iron (Fe),
      manganese (Mn) and antimony (Sb). The concentrations of metals in wheat grain
      were predicted using the topsoil and atmospheric fall-out composition with
      R(2)=0.90, with the latter being the best explanatory variable. The present study
      highlights the potential health hazards of wheat consumption (Environmental
      Protection Agency) by the assessment of heavy metals in bulk atmospheric
      deposition.

PMID- 22390957
TI  - Continuous degradation of a mixture of sulfonamides by Trametes versicolor and
      identification of metabolites from sulfapyridine and sulfathiazole.
AB  - In this study, we assessed the degradation of the sulfonamides sulfapyridine
      (SPY) and sulfathiazole (STZ) by the white-rot fungus Trametes versicolor.
      Complete degradation was accomplished in fungal cultures at initial pollutant
      concentrations of approximately 10 mg L(-1), although a longer period of time was
      needed to completely remove STZ in comparison to SPY. When cytochrome P450
      inhibitors were added to the fungal cultures, STZ degradation was partially
      suppressed, while no additional effect was observed for SPY. Experiments with
      purified laccase and laccase mediators caused the removal of greater than 75% of
      each antibiotic. Ultra-performance liquid chromatography-quadupole time of flight
      mass spectrometry (UPLC-QqTOF-MS) analyses allowed the identification of a total
      of eight degradation intermediates of SPY in both the in vivo and the laccase
      experiments, being its desulfonated moiety the commonly detected product. For
      STZ, a total of five products were identified. A fluidized bed reactor with T.
      versicolor pellets degraded a mixture of sulfonamides (SPY, STZ and
      sulfamethazine, SMZ) by greater than 94% each at a hydraulic residence time of 72
      h. Because wastewater contains many diverse pollutants, these results highlight
      the potential of T. versicolor as a bioremediation agent not only for the removal
      of antibiotics but also for the elimination of a wide range of contaminants.

PMID- 22390958
TI  - Clinical performance of an orthokeratology lens fitted with the aid of a computer
      software in Chinese children.
AB  - PURPOSE: To report the clinical performance of the orthokeratology (ortho-k) lens
      fitted with computer assisted system after 1-month of lens wear, in a group of
      children undergoing ortho-k treatment in a 2-year randomized myopic control
      study. METHOD: Children aged 6-11 years old were fitted with the ortho-k lenses
      using computerized fitting. The initial myopia was 4.00-0.50 D and the initial
      refractive astigmatism was within 1.25 D. Lens performance, in terms of
      centration, myopic reduction, vision, ocular health status and lens binding
      incidence, was evaluated at one night, one week and one month after lens wear.
      Only data from the right eye was presented. RESULTS: The initial spherical
      equivalent refraction (SER) for the 51 subjects was -2.29 +/- 0.81 D. The first
      fit success rate was 90%. The reduction of SER after one night and one week
      aftercare visit were 57% and 81%, respectively. At the one month visit, the mean
      reduction in SER was 89% with unaided logMAR visual acuity of 0.03 +/- 0.11. Mild
      central corneal staining was found in 9-20% of the subjects at the aftercare
      visits. The incidences of lens binding at one night, one week and one month
      aftercare visits were 17%, 39% and 30%, respectively. CONCLUSIONS: Computer
      assisted system for Menicon Z Night lens fitting gave a high first fit success
      rate. Menicon Z Night lens was effective in myopic reduction and provided stable
      vision after one week of lens wear. Ocular health of the subjects after lens wear
      was generally unremarkable.

PMID- 22390959
TI  - Functional electrical stimulation applied to gluteus medius and tibialis anterior
      corresponding gait cycle for stroke.
AB  - The purpose of this study was to determine the influence of functional electrical
      stimulation (FES) applied to the tibialis anterior and gluteus medius muscles on
      the improvement of the spatiotemporal parameters of gait in individuals with a
      hemiparetic stroke. Thirty-six patients who had suffered a hemiparesis post
      stroke were enrolled in this study. The participants walked at a self-selected
      velocity on three different FES applications: (1) FES-triggered gait on the
      gluteus medius in the stance phase and the tibialis anterior in the swing phase
      (GM+TA), (2) FES-triggered gait on the tibialis anterior in the swing phase (TA
      only), and (3) gait without FES-triggered (Non-FES). FES was triggered when the
      heel in the affected lower limb was placed in contact with an on or off foot
      switch sensor. The effect of FES applications was assessed using GAITRite for
      spatiotemporal data. The gait speed, cadence, and stride length were
      significantly higher under the GM+TA condition than under the TA only and None
      FES conditions. The gait speed, cadence and stride length were increased
      significantly in the TA only condition compared with the Non-FES condition. The
      double support time and gait symmetry were significantly improved in the GM+TA
      condition compared to the TA only and Non-FES conditions. These findings suggest
      that walking with FES of the gluteus medius in the stance phase and tibialis
      anterior in the swing phase can improve the spatiotemporal parameters of gait in
      individuals with hemiparetic stroke.

PMID- 22390960
TI  - Time-of-day influences postural balance in older adults.
AB  - BACKGROUND: Postural balance assessments are performed in both clinical and basic
      research settings on a daily basis. During a 24-h time span our physiology and
      physical performance undergo radical changes as we are influenced by the
      circadian rhythm. The time-of-day interaction on postural balance is unknown in
      older adults. The aim of this study was to investigate the time-of-day effect on
      postural balance in older adults. METHODS: Center of pressure (CoP) excursion was
      measured (100 Hz) by force plate analysis in 34 older adults during 30 s of
      narrow quiet bilateral stance. Measurements were performed around 9a.m., 12.30
      p.m. and 4 p.m. on the same day. Postural balance was quantified by velocity
      moment, confidence ellipse area, total sway area and total sway length. RESULTS:
      An overall significant time-of-day (between 9 a.m. and 4 p.m.) effect was
      observed for velocity-moment (mm(2)/s) 57 +/- 27-65 +/- 29 (p = 0.001),
      confidence ellipse area (mm(2)) 36 +/- 16-44 +/- 19 (p < 0.001), total sway area
      (mm(2)) 548 +/- 263-627 +/- 285 (p = 0.001) and total sway length (mm) 373 +/-
      120-379 +/- 113 (p = 0.037). The variation of postural balance was mostly
      pronounced from midday (12.30 p.m.) toward the afternoon (4 p.m.) in all sway
      parameters. Specifically between 12.30 p.m. and 4 p.m. confidence ellipse area
      increased by 18.5%, total sway area by 17.1%, velocity-moment by 15.8% and total
      sway length by 4.6%. No differences were observed between 9 a.m. and 12.30 p.m.
      in any of the sway parameters. CONCLUSIONS: This study demonstrates that time-of
      day influences postural balance in older adults. These findings have important
      scientific and clinical relevance, as they imply that time-of-day should be a
      controlled factor when assessing postural balance in older adults.

PMID- 22390961
TI  - Unilateral eccentric exercise of the knee flexors affects muscle activation
      during gait.
AB  - Uni-lateral muscle soreness is common yet the effects on gait or
      electromyographic (EMG) activity are unknown. The purpose of our study was to
      induce delayed onset muscle soreness (DOMS) in the knee flexor group and measure
      the resultant change in EMG activity and knee motion during gait. Nine healthy
      subjects participated in the study. Measures of function, evoked tenderness of
      the biceps femoris, as well as knee angle, and EMG activity during gait were
      assessed prior and 48 h after an eccentric exercise protocol. DOMS was induced
      unilaterally in the knee flexors using an isokinetic dynamometer and subjects
      exercised until they could not generate 50% of their maximal voluntary isometric
      contraction (MVIC). There was a significant decrease in biceps femoris activity
      after DOMS during the last phase of gait. Moreover, there was a day * phase
      interaction for gastrocnemius activity with the last two phases displaying an
      increase in activity. There was no significant change in knee angle during gait.
      The decrease in biceps femoris activity as well as the increase in gastrocnemius
      activity could be evidence of a protective mechanism designed to decrease
      activity of the sore muscle while increasing the activity of a synergistic
      muscle.

PMID- 22390962
TI  - Characterization of spatiotemporally complex gait patterns using cross
      correlation signatures.
AB  - We hypothesize that spatiotemporal joint coupling patterns during gait are
      closely associated with musculoskeletal injury mechanics. Previous studies
      examining joint coupling, have primarily focused on coupling between single pairs
      of neighboring body segments or joints; thus falling short of characterizing the
      full spatiotemporal complexity across the entire gait apparatus. This study
      proposes the reliance on properties of the temporal cross-correlation of distinct
      joint variables as a means to characterize and detect differences in multiple
      segmental coupling pairs and to quantify how these couplings change between
      different gait conditions or test groups. In particular, for each subject, a
      characteristic diagram array is obtained whose entries include the maximum values
      of the cross-correlation between all pairs of joint variables as well as the
      associated phase shifts at which these maxima are recorded. Paired t-tests are
      then used to highlight significant differences in the corresponding entries
      between two gait conditions. In the present study, this technique was applied to
      angular displacement and velocity histories across 12 lower extremity joint
      variables, for healthy subjects with and without a brace on the right knee. As
      expected, the statistical analysis indicated that the temporal cross-correlations
      associated with the right knee-angle variables differed the most between the two
      gait conditions. In addition, significant differences (p<0.01) were found in the
      coupling between other pairs of joint variables, establishing a characteristic
      spatiotemporal signature for the changes from normative gait that result from
      reduced mobility at the knee.

PMID- 22390963
TI  - Egg consumption and the risk of type 2 diabetes mellitus: a case-control study.
AB  - OBJECTIVE: Type 2 diabetes mellitus appears to involve an interaction between
      susceptible genetic backgrounds and environmental factors including highly
      calorific diets. As it is important to identify modifiable risk factors that may
      help reduce the risk of type 2 diabetes mellitus, the aim of the present study
      was to determine the association between egg consumption and the risk of type 2
      diabetes mellitus. DESIGN: A specifically designed questionnaire was used to
      collect information on possible risk factors of type 2 diabetes mellitus. The
      odds ratios and 95 % confidence intervals for type 2 diabetes mellitus were
      calculated by conditional logistic regression. SETTING: A case-control study in a
      Lithuanian out-patient clinic was performed in 2001. SUBJECTS: A total of 234
      cases with a newly confirmed diagnosis of type 2 diabetes mellitus and 468
      controls free of the disease. RESULTS: Variables such as BMI, family history of
      diabetes, cigarette smoking, education, morning exercise and plasma TAG level
      were retained in multivariate logistic regression models as confounders because
      their inclusion changed the value of the odds ratio by more than 10 % in any
      exposure category. After adjustment for possible confounders more than twofold
      increased risk of type 2 diabetes mellitus was determined for individuals
      consuming 3-4.9 eggs/week (OR = 2.60; 95 % CI 1.34, 5.08) and threefold increased
      risk of the disease was determined for individuals consuming >=5 eggs/week (OR =
      3.02; 95 % CI 1.14, 7.98) compared with those eating <1 egg/week. CONCLUSIONS:
      Our data support a possible relationship of egg consumption and increased risk of
      type 2 diabetes mellitus.

PMID- 22390964
TI  - Assessment of intrastromal corneal ring segment position with anterior segment
      optical coherence tomography.
AB  - BACKGROUND AND OBJECTIVE: To examine the exact position of implanted Keraring
      (Mediphacos, Belo Horizonte, Brazil) segments by high-resolution anterior segment
      optical coherence tomography (AS-OCT). PATIENTS AND METHODS: This study included
      17 eyes of 13 patients with keratoconus who underwent uneventful intracorneal
      ring segment implantation with the aid of femtosecond laser. Eyes were evaluated
      by AS-OCT at the third postoperative month. Distance from the apex of the
      triangular cross-section of the ring segment to the anterior corneal surface and
      distances from two basal corners to the posterior corneal surface were measured.
      RESULTS: Distance from apex to anterior corneal surface (263.1 +/- 42.9 MUm) was
      significantly smaller than target depth calculated intraoperatively (356.9 +/-
      35.7 MUm, P < .001). Distance between outer basal corner and posterior corneal
      surface was significantly greater than distance between inner basal corner and
      posterior corneal surface. CONCLUSION: High-resolution AS-OCT is a rapid,
      convenient, and valuable technique in the follow-up of patients with implanted
      Keraring segments that may be helpful in predicting ring-related complications.

PMID- 22390965
TI  - Quantification of pupil parameters in diseased and normal eyes with near infrared
      iris transillumination imaging.
AB  - BACKGROUND AND OBJECTIVE: To investigate near infrared iris transillumination
      (NIRit) imaging as a new method to quantify pupil shape, size, and position
      because the imaging modality can uniquely provide simultaneous information
      regarding iris structural details that influence pupil characteristics and
      because exploration of related techniques could promote discovery helpful to
      clinical research and care. PATIENTS AND METHODS: Digital NIRit images of normal
      and diseased eyes were used along with computer-assisted techniques to quantify
      four primary pupil parameters, including pupil roundness (PR), pupil ovalness
      (PO), pupil size (PS), and pupil eccentricity (PE). A combined measure of PR and
      PO was also developed (the pupil circularity index [PCI]). Repeatability of the
      measures was studied and example analyses were performed. RESULTS: Pupil measures
      could be calculated for right eyes of 307 subjects (164 normal, 143 other), with
      fewer than 0.5% exclusions due to image quality. Repeatability study did not show
      significant bias (P < .05) for any of the four primary measures. Example analyses
      could show age-associated differences in pupil shape (>= 50 year olds had less
      regular pupils than < 50 year olds: median PCI = 0.009 vs 0.006; P < .01) and
      that a group of pigment dispersion syndrome subjects (n = 27) had less regular
      pupils than a group of matched controls (PO = 0.9966 vs 0.9990; P < .05).
      CONCLUSION: Digital NIRit imaging can provide novel, reliable, and informative
      methods to quantify pupil characteristics while providing simultaneous
      information about iris structure that may influence these parameters.

PMID- 22390966
TI  - Disease targeting therapies in patients with Eisenmenger syndrome: response to
      treatment and long-term efficiency.
AB  - OBJECTIVES: To examine long-term efficacy of disease targeting therapies (DTT) in
      patients with Eisenmenger syndrome. METHODS: All adult patients with Eisenmenger
      syndrome treated with DTT at our institution were included. Functional class
      (FC), oxygen saturation and 6-minute walk test distance (6 MWTd) were analysed
      retrospectively. RESULTS: Between 2002 and 2010, 79 Eisenmenger patients (21
      males, 16 with Down syndrome) aged 34 +/- 10 years (range 17-68 years) were
      included. Median follow-up was 3.3 years (range 0.2 to 8.9 years). 6 MWTd
      increased early after initiation of DTT, with a plateau after approximately 3
      years and no obvious trend towards a deterioration on average during longer-term
      follow-up. Two patients died during follow-up and escalation of treatment was
      required in 18 patients after a median period of 2.5 years. Escalation of therapy
      was also associated with an increase in 6 MWTd. In addition, FC improved on DTT
      and oxygen saturation, increased, both at rest and peak exercise. This effect was
      more pronounced in the patients with the lowest baseline oxygen saturation at
      rest. CONCLUSIONS: Long-term DTT is safe and improves objective exercise capacity
      and subjective symptoms. Response to DTT was typically observed early after
      initiation of DTT and was, on average, maintained longer-term. However, 1 in 5
      patients required escalation of DTT, with time, due to symptomatic deterioration
      and this was associated with an afresh improvement in 6 MWTd.

PMID- 22390967
TI  - Abnormal right atrial and right ventricular diastolic function relate to impaired
      clinical condition in patients operated for tetralogy of Fallot.
AB  - BACKGROUND: Atrial enlargement may reflect ventricular diastolic dysfunction.
      Although patients with tetralogy of Fallot (TOF) have been studied extensively,
      little is known about atrial size and function. We assessed bi-atrial size and
      function in patients after TOF repair, and related them to biventricular systolic
      and diastolic function, and clinical parameters. METHODS: 51 Patients (21 +/- 8
      years) and 30 healthy controls (31 +/- 7 years) were included and underwent
      magnetic resonance imaging to assess bi-atrial and biventricular size, systolic
      and diastolic function. Patients also underwent exercise testing, and N-terminal
      prohormone brain natriuretic peptide (NT-proBNP) assessment. RESULTS: In
      patients, right atrial (RA) minimal volume (34 +/- 8 ml/m(2) vs. 28 +/- 8
      ml/m(2), p=0.001) and late emptying fraction were increased; RA early emptying
      fraction was decreased. Patients had longer right ventricular (RV) deceleration
      time (0.24 +/- 0.10 vs. 0.13 +/- 0.04, p<0.001), reflecting impaired RV
      relaxation, and larger RV volumes. Patients with end-diastolic forward flow
      (EDFF) had larger RA and RV size, abnormal RA emptying, higher NT-proBNP levels,
      higher VE/VCO2 slope (ventilatory response to carbon dioxide production), and the
      most abnormal LV diastolic function (impaired compliance). Patients with abnormal
      RA emptying (reservoir function <30% and pump function >24%) had higher NT-proBNP
      levels and worse exercise capacity. RA minimal volume was associated with RV end
      diastolic volume (r=0.35, p=0.013). CONCLUSIONS: In TOF patients with moderate RV
      dilatation, abnormal bi-atrial function and biventricular diastolic dysfunction
      are common. Abnormal RA emptying was associated with signs of impaired clinical
      condition, as was the presence of EDFF. These parameters, together with RA
      enlargement, could serve as useful markers for clinically relevant RV diastolic
      dysfunction.

PMID- 22390968
TI  - Cardiogenic shock induced by basal septal hypertrophy and left ventricular
      outflow tract dynamic obstruction in a critically ill patient with sepsis.

PMID- 22390969
TI  - The Sum1/Ndt80 transcriptional switch and commitment to meiosis in Saccharomyces
      cerevisiae.
AB  - Cells encounter numerous signals during the development of an organism that
      induce division, differentiation, and apoptosis. These signals need to be present
      for defined intervals in order to induce stable changes in the cellular
      phenotype. The point after which an inducing signal is no longer needed for
      completion of a differentiation program can be termed the "commitment point."
      Meiotic development in the yeast Saccharomyces cerevisiae (sporulation) provides
      a model system to study commitment. Similar to differentiation programs in
      multicellular organisms, the sporulation program in yeast is regulated by a
      transcriptional cascade that produces early, middle, and late sets of sporulation
      specific transcripts. Although critical meiosis-specific events occur as early
      genes are expressed, commitment does not take place until middle genes are
      induced. Middle promoters are activated by the Ndt80 transcription factor, which
      is produced and activated shortly before most middle genes are expressed. In this
      article, I discuss the connection between Ndt80 and meiotic commitment. A
      transcriptional regulatory pathway makes NDT80 transcription contingent on the
      prior expression of early genes. Once Ndt80 is produced, the recombination
      (pachytene) checkpoint prevents activation of the Ndt80 protein. Upon activation,
      Ndt80 triggers a positive autoregulatory loop that leads to the induction of
      genes that promote exit from prophase, the meiotic divisions, and spore
      formation. The pathway is controlled by multiple feed-forward loops that give
      switch-like properties to the commitment transition. The conservation of
      regulatory components of the meiotic commitment pathway and the recently reported
      ability of Ndt80 to increase replicative life span are discussed.

PMID- 22390970
TI  - Into the eye of the cytokine storm.
AB  - The cytokine storm has captured the attention of the public and the scientific
      community alike, and while the general notion of an excessive or uncontrolled
      release of proinflammatory cytokines is well known, the concept of a cytokine
      storm and the biological consequences of cytokine overproduction are not clearly
      defined. Cytokine storms are associated with a wide variety of infectious and
      noninfectious diseases. The term was popularized largely in the context of avian
      H5N1 influenza virus infection, bringing the term into popular media. In this
      review, we focus on the cytokine storm in the context of virus infection, and we
      highlight how high-throughput genomic methods are revealing the importance of the
      kinetics of cytokine gene expression and the remarkable degree of redundancy and
      overlap in cytokine signaling. We also address evidence for and against the role
      of the cytokine storm in the pathology of clinical and infectious disease and
      discuss why it has been so difficult to use knowledge of the cytokine storm and
      immunomodulatory therapies to improve the clinical outcomes for patients with
      severe acute infections.

PMID- 22390971
TI  - Emerging role of ubiquitination in antiviral RIG-I signaling.
AB  - Detection of viruses by the innate immune system involves the action of
      specialized pattern recognition receptors. Intracellular RIG-I receptors sense
      the presence of viral nucleic acids in infected cells and trigger signaling
      pathways that lead to the production of proinflammatory and antiviral proteins.
      Over the past few years, posttranslational modification of RIG-I and downstream
      signaling proteins by different types of ubiquitination has been found to be a
      key event in the regulation of RIG-I-induced NF-kappaB and interferon regulatory
      factor 3 (IRF3) activation. Multiple ubiquitin ligases, deubiquitinases, and
      ubiquitin binding scaffold proteins contribute to both positive and negative
      regulation of the RIG-I-induced antiviral immune response. A better understanding
      of the function and activity of these proteins might eventually lead to the
      development of novel therapeutic approaches for management of viral diseases.

PMID- 22390974
TI  - 'PUFA-GPR40-CREB signaling' hypothesis for the adult primate neurogenesis.
AB  - Despite the well-known effects of polyunsaturated fatty acids (PUFA) on synaptic
      plasticity, PUFA-modulated signaling mechanism is unknown especially in humans.
      In 2003, three groups reported that G protein-coupled receptor 40 (GPR40) induces
      Ca2+ mobilization in response to PUFA. Although GPR40 gene is abundantly
      expressed in the primate brain, it is negligible in the rodent brain. Diverse
      PUFA including docosahexaenoic acid (DHA) are in vitro ligands for GPR40, but
      nobody knows its downstream pathway. cAMP-response element binding protein (CREB)
      is a transcription factor transmitting extracellular signals to change gene
      expression. Although PUFA, transported by fatty acid binding proteins (FABP),
      directly phosphorylate CREB in rodents, hydrophobic PUFA cannot access to the
      nuclei in the primate neurons because of lack of a cargo protein. Ischemia
      enhanced adult neurogenesis in monkeys showed concomitant upregulation of GPR40
      and phosphorylated CREB, and localization of both in the neurogenic niche. Here,
      'PUFA-GPR40-CREB signaling' hypothesis was highlighted as a regulator of adult
      neurogenesis specific for primates.

PMID- 22390975
TI  - The growth pattern and fuel life cycle analysis of the electricity consumption of
      Hong Kong.
AB  - As the consumption of electricity increases, air pollutants from power generation
      increase. In metropolitans such as Hong Kong and other Asian cities, the surge of
      electricity consumption has been phenomenal over the past decades. This paper
      presents a historical review about electricity consumption, population, and
      change in economic structure in Hong Kong. It is hypothesized that the growth of
      electricity consumption and change in gross domestic product can be modeled by 4
      parameter logistic functions. The accuracy of the functions was assessed by
      Pearson's correlation coefficient, mean absolute percent error, and root mean
      squared percent error. The paper also applies the life cycle approach to
      determine carbon dioxide, methane, nitrous oxide, sulfur dioxide, and nitrogen
      oxide emissions for the electricity consumption of Hong Kong. Monte Carlo
      simulations were applied to determine the confidence intervals of pollutant
      emissions. The implications of importing more nuclear power are discussed.

PMID- 22390976
TI  - Comparison of a bioremediation process of PAHs in a PAH-contaminated soil at
      field and laboratory scales.
AB  - A laboratory experiment was carried on the same initial soil and at the same time
      than a windrow treatment in order to compare results at field and laboratory
      scales for a soil mainly contaminated with PAHs. After 6 months, laboratory
      experiments gave similar but less scattered results than those obtained in the
      field indicating that the field biotreatment was well optimised. The total amount
      of PAHs degraded after 6 months was ca. 90% and degradation rates followed a
      negative exponential trend. Relative degradation rates of 3- and 4-ring PAHs were
      about 32 and 7.2 times greater than those of 5- and 6-ring PAHs, respectively.
      With respect to the bacterial community, bacteria belonging to Gamma
      proteobacteria persisted whereas Beta-proteobacteria appeared after three months
      of biotreatment when PAH concentration was low enough to render the soil non
      ecotoxic.

PMID- 22390972
TI  - The multiple signaling systems regulating virulence in Pseudomonas aeruginosa.
AB  - Cell-to-cell communication is a major process that allows bacteria to sense and
      coordinately react to the fluctuating conditions of the surrounding environment.
      In several pathogens, this process triggers the production of virulence factors
      and/or a switch in bacterial lifestyle that is a major determining factor in the
      outcome and severity of the infection. Understanding how bacteria control these
      signaling systems is crucial to the development of novel antimicrobial agents
      capable of reducing virulence while allowing the immune system of the host to
      clear bacterial infection, an approach likely to reduce the selective pressures
      for development of resistance. We provide here an up-to-date overview of the
      molecular basis and physiological implications of cell-to-cell signaling systems
      in Gram-negative bacteria, focusing on the well-studied bacterium Pseudomonas
      aeruginosa. All of the known cell-to-cell signaling systems in this bacterium are
      described, from the most-studied systems, i.e., N-acyl homoserine lactones
      (AHLs), the 4-quinolones, the global activator of antibiotic and cyanide
      synthesis (GAC), the cyclic di-GMP (c-di-GMP) and cyclic AMP (cAMP) systems, and
      the alarmones guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate
      (pppGpp), to less-well-studied signaling molecules, including diketopiperazines,
      fatty acids (diffusible signal factor [DSF]-like factors), pyoverdine, and
      pyocyanin. This overview clearly illustrates that bacterial communication is far
      more complex than initially thought and delivers a clear distinction between
      signals that are quorum sensing dependent and those relying on alternative
      factors for their production.

PMID- 22390977
TI  - Changes in stability of the DPPC monolayer during its contact with the liquid
      phase.
AB  - The Langmuir-Blodgett (LB) method was applied and a few series of advancing and
      receding contact angles measurements as a function of time were performed to
      examine stability of model phospholipid monolayers during their contact with
      water, formamide and diiodomethane droplets. The studied monolayer was single
      component saturated phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
      (DPPC) transferred onto mica surface. When the time of the contact angle
      measurements is prolonged in these systems, some changes in the DPPC layer
      structure occur due to the contact with probing liquid, especially water, which
      is reflected in the changes of measured contact angle. Generally, with increasing
      time of the droplet contact with DPPC monolayer the contact angle decreases. Some
      correlation between the contact angle decrease and molecular rearrangements of
      initially hydrophobic DPPC monolayer is observed if it comes into contact with
      water. On the other hand, the contact angle completed within the first few
      seconds can faithfully reflect the original structure of the layer, and thus its
      energetic state, because during this time the structure changes are
      insignificant. Basing on the measured contact angles the monolayer's apparent
      surface free energy and its components, corresponding to different contact times
      of the droplets, were calculated. These results are helpful for better
      characterization of the processes taking place in the phospholipid layers being
      in contact with polar (water and formamide) and nonpolar (diiodomethane) liquids.

PMID- 22390978
TI  - Interplay of early-life nutritional programming on obesity, inflammation and
      epigenetic outcomes.
AB  - The huge health burden accompanying obesity is not only attributable to
      inadequate dietary and sedentary lifestyle habits, since a predisposing genetic
      make-up and other putative determinants concerning easier weight gain and fat
      deposition have been reported. Thus, several investigations aiming to understand
      energy metabolism and body composition maintenance have been performed
      considering the participation of perinatal nutritional programming and epigenetic
      processes as well as inflammation phenomena. The Developmental Origins of Health
      and Disease hypothesis and inheritance-oriented investigations concerning gene
      nutrient interactions on energy homoeostasis and metabolic functions have
      suggested that inflammation could be not only a comorbidity of obesity but also a
      cause. There are several examples about the role of nutritional interventions in
      pregnancy and lactation, such as energetic deprivation, protein restriction and
      excess fat, which determine a cluster of disorders affecting energy efficiency in
      the offspring as well as different metabolic pathways, which are mediated by
      epigenetics encompassing the chromatin information encrypted by DNA methylation
      patterns, histone covalent modifications and non-coding RNA or microRNA.
      Epigenetic mechanisms may be boosted or impaired by dietary and environmental
      factors in the mother, intergenerationally or transiently transmitted, and could
      be involved in the obesity and inflammation susceptibility in the offspring. The
      aims currently pursued are the early identification of epigenetic biomarkers
      concerned in individual's disease susceptibility and the description of protocols
      for tailored dietary treatments/advice to counterbalance adverse epigenomic
      events. These approaches will allow diagnosis and prognosis implementation and
      facilitate therapeutic strategies in a personalised 'epigenomically modelled'
      manner to combat obesity and inflammation.

PMID- 22390979
TI  - Scattering matrices of Lamb waves at irregular surface and void defects.
AB  - Time-harmonic solution of Lamb wave scattering in a plane-strain waveguide with
      irregular thickness is investigated based on stair-step discretization and
      stepwise mode matching. The transfer relations of the transmission matrices and
      reflection matrices are derived in both directions of the waveguide. With these,
      an explicit expression of the scattering matrix is derived. When the scattering
      region of an inner irregular defect is geometrically divided into several parts
      composed of sub-waveguides with variable thicknesses and void regions with
      vertical free edges corresponding to the plate surfaces, the scattering matrix of
      the whole region could then be derived by modal matching along the artificial
      boundaries, as explicit functions of all the scattering matrices of the sub
      waveguides and reflection matrices of the free edges. The effectiveness of the
      formulation is examined by numerical examples; the calculated scattering
      coefficients are in good accordance with those obtained from numerical simulation
      models.

PMID- 22390973
TI  - Phylogenetic framework and molecular signatures for the main clades of the phylum
      Actinobacteria.
AB  - The phylum Actinobacteria harbors many important human pathogens and also
      provides one of the richest sources of natural products, including numerous
      antibiotics and other compounds of biotechnological interest. Thus, a reliable
      phylogeny of this large phylum and the means to accurately identify its different
      constituent groups are of much interest. Detailed phylogenetic and comparative
      analyses of >150 actinobacterial genomes reported here form the basis for
      achieving these objectives. In phylogenetic trees based upon 35 conserved
      proteins, most of the main groups of Actinobacteria as well as a number of their
      superageneric clades are resolved. We also describe large numbers of molecular
      markers consisting of conserved signature indels in protein sequences and whole
      proteins that are specific for either all Actinobacteria or their different
      clades (viz., orders, families, genera, and subgenera) at various taxonomic
      levels. These signatures independently support the existence of different
      phylogenetic clades, and based upon them, it is now possible to delimit the
      phylum Actinobacteria (excluding Coriobacteriia) and most of its major groups in
      clear molecular terms. The species distribution patterns of these markers also
      provide important information regarding the interrelationships among different
      main orders of Actinobacteria. The identified molecular markers, in addition to
      enabling the development of a stable and reliable phylogenetic framework for this
      phylum, also provide novel and powerful means for the identification of different
      groups of Actinobacteria in diverse environments. Genetic and biochemical studies
      on these Actinobacteria-specific markers should lead to the discovery of novel
      biochemical and/or other properties that are unique to different groups of
      Actinobacteria.

PMID- 22390980
TI  - Cuspal deflection and microleakage in premolar teeth restored with bulk-fill
      flowable resin-based composite base materials.
AB  - OBJECTIVES: To assess the cuspal deflection and cervical microleakage of
      standardised Class II cavities incrementally filled with a dimethacrylate RBC or
      bulk-fill flowable RBC bases. METHODS: Twenty-four sound upper premolar teeth
      with Class II cavities were allocated to three groups (n=8). Restoration of the
      teeth involved the placement of an RBC (GrandioSO) in eight oblique increments
      (Group A) or Groups B and C were restored to within 2 mm of the palatal cusp in a
      single increment with bulk-fill flowable RBC bases (SDR and x-tra base) before
      the two occlusal cavity increments were placed with GrandioSO. Buccal and palatal
      cusp deflections were recorded postirradiation using a twin channel deflection
      measuring gauge. Following restoration, the teeth were thermocycled, immersed in
      0.2% basic fuchsin dye for 24h, sectioned and examined for cervical microleakage.
      RESULTS: The mean total cuspal deflection for the oblique incremental restoration
      technique was 11.26 (2.56) MUm (Group A) and 4.63 (1.19) MUm (Group B) and 4.73
      (0.99) MUm (Group C) for the bulk-fill flowable RBC bases. A significant increase
      in the mean total cuspal deflection for the incrementally filled GrandioSO
      compared with the SDR (P=0.007) and x-tra base (P=0.005) restored teeth was
      evident. No significant difference in the cervical microleakage scores was
      recorded between groups AC (P>0.05). CONCLUSIONS: The bulk-fill flowable RBC
      bases significantly reduced cuspal deflection compared with a conventional RBC
      restored in an oblique incremental filling technique with no associated change in
      cervical microleakage recorded.

PMID- 22390981
TI  - Fungicidal amounts of antifungals are released from impregnated denture lining
      material for up to 28 days.
AB  - OBJECTIVES: The aim of this study was to investigate the efficacy of a polymeric
      delivery system impregnated with chlorhexidine or fluconazole against Candida
      species. METHODS: Self-cure poly-ethyl methacrylate and tetrahydro-furfuryl
      methacrylate (PEM/THFM) discs impregnated with pure fluconazole substance (FLUp),
      fluconazole powder from capsules (FLUc) or chlorhexidine powder (CHX) were
      incubated in water for up to 28 days at 37  degrees C. The water was replaced at
      24h and 3, 7, 14, 21, 28 days. The amount of released drugs and antifungal
      activity of the leachates was measured by bioassay. The minimal inhibitory
      concentration (MIC) of each drug for 46 Candida isolates was determined and
      compared to the released concentrations. RESULTS: A total of 53.0% of CHX, 38.5%
      of FLUc and 13.2% of FLUp impregnated into the discs was leached during the 28
      day incubation. Of the total amount leached, 71.8% of CHX, 75.1% of FLUc and
      70.5% of FLUp was released during the first week of incubation. Antifungal
      activity was confirmed for up to 28 days. CONCLUSION: Both chlorhexidine and
      fluconazole become readily leached from PEM/THFM polymer up to four weeks and
      that the polymerisation of the acrylic does not affect the antimicrobial activity
      of the agents. Importantly, the amount of drugs released exceeded the MICs of
      most isolates also during the fourth week of incubation. CLINICAL SIGNIFICANCE:
      These findings indicate the feasibility of this treatment modality for oral
      candidal infections, especially denture stomatitis. But further in vivo work is
      warranted to determine its clinical relevance and applicability.

PMID- 22390983
TI  - Remodelling of the sinotubular junction to correct aortic insufficiency.

PMID- 22390982
TI  - Paying more attention to attention: towards more comprehensive cognitive
      translation using mouse models of Alzheimer's disease.
AB  - The cognitive phenotyping of mouse models of Alzheimer's disease (AD) currently
      focuses on impairments in learning and memory. However, AD is not simply a memory
      disorder, but other cognitive domains, and in particular attention, can also be
      impaired even at very early stages of the disease. In this review we argue for
      the benefits of including other constructs, and in particular attention, in
      preclinical studies to identify drug targets and disease mechanisms of AD in
      mouse models. First we give a brief account of the evidence for attentional
      deficits in AD; we then summarise methods to assess equivalent aspects of
      attention in mice, followed by a review of recent evidence for attentional
      impairments in widely used mouse models of AD. We conclude by suggesting that a
      multidimensional approach to cognitive assessment in preclinical models, in which
      a number of aspects of cognition are investigated while confounding factors are
      minimized, is becoming increasingly feasible and may contribute significantly
      towards the development of more targeted therapeutic interventions.

PMID- 22390984
TI  - The combination of polytetrafluoroethylene mesh and titanium rib implants: an
      innovative process for reconstructing large full thickness chest wall defects.
AB  - OBJECTIVES: The reconstruction of large full thickness chest wall defect after
      resection of T3/T4 non-small cell lung cancer (NSCLC) or primary chest wall
      tumours presents a technical challenge for thoracic surgeons and is a critical
      factor in determining post-operative outcome. When the defect is large,
      complications are common with a 27% mean rate of respiratory morbidity. METHODS:
      Since 2006, 31 patients underwent reconstruction for wide chest wall defects
      using titanium implants and strong mesh. The reconstruction was achieved using a
      layer of polytetrafluoroethylene or a XCM biologic tissue mesh shaped to match
      the defect and sutured under maximum tension to re-establish the skeletal
      continuity. The mesh was placed close to the lung and was fixed onto the bony
      framework and onto the titanium plate. In one case, we used XCM biologic tissue
      because of a large infected T3 NSCLC. A horizontal titanium rib osteosynthesis
      system was used to reestablish the rigidity of the thoracic wall by bridging the
      defect except for one case in which we use a vertical rib osteosynthesis system.
      RESULTS: Twenty-six patients underwent a complete R0 resection with the removal
      of a mean of 4.67 +/- 1.5 [3-9] ribs, including the sternum in 14 cases. The mean
      defect area was 198 +/- 91.2 [95-400] cm&sup2;. Reconstruction required a mean of
      2.06 +/- 1.1 [1-4] titanium plates. There were two cases of deep wound infection
      that required surgical removal of the osteosynthesis system in one patient. Only
      one patient developed a major complication in the form of respiratory failure.
      There were two postoperative deaths neither of which was directly related to the
      surgical procedure. CONCLUSIONS: Our experience and initial results show that
      titanium rib osteosynthesis in combination with strong biologic or synthetic mesh
      can easily and safely be used in a one-stage procedure for the reconstruction of
      major chest wall defects.

PMID- 22390986
TI  - Age and neo-adjuvant chemotherapy increase the risk of atrial fibrillation
      following oesophagectomy.
AB  - OBJECTIVES: Atrial tachyarrhythmias occur in up to 25% of patients after major
      thoracic surgery. We examined risk factors for new-onset atrial fibrillation (AF)
      following oesophagectomy in an attempt to guide prophylactic use of anti
      arrhythmic strategies. METHODS: Data were extracted from a database of patients
      who underwent oesophagectomy between 1991 and 2009. Patients with pre-operative
      arrhythmias were excluded leaving 997 patients for further analysis. Univariate
      and multivariate logistic regression analyses were performed to identify factors
      predicting AF, and receiver operating characteristic curves were generated from a
      model using these predictors. Statistical significance was reflected in a P-value
      of <0.05. RESULTS: Patients who developed AF (n = 209; 20.96%) were older (median
      age 70.54 years vs. 66.9 years; P < 0.01) and included 141 males (67.4%) (P =
      0.11). Patients with AF were noted to have a higher in-hospital mortality rate (n
      = 17; 8.1% vs. n = 34; 4.8%) (P = 0.04) and a longer stay in hospital (14 days
      vs. 12 days; P < 0.01). Multivariate analysis identified advanced age and neo
      adjuvant chemotherapy to be independent predictors of the risk of developing AF.
      Assessment of discriminative ability of a predictive model revealed a c-statistic
      of just 0.62. CONCLUSIONS: Despite the identification of age and neo-adjuvant
      chemotherapy as predictors of AF, the moderate discriminative ability of
      predictive modelling does not support the use of prophylactic anti-arrhythmic
      drugs. However, the high incidence of AF after major thoracic surgery makes it
      necessary to understand its underlying mechanisms better before prophylactic
      strategies are considered.

PMID- 22390987
TI  - Incoming pathogens team up with harmless 'resident' bacteria.
AB  - Microbial diseases occur as a result of multifarious host-pathogen interactions.
      However, invading pathogens encounter a large number of different harmless and
      beneficial bacterial species, which colonize and reside in the host.
      Surprisingly, there has been little study of the possible interactions between
      incoming pathogens and the resident bacterial community. Recent studies have
      revealed that resident bacteria assist different types of incoming pathogens via
      a wide variety of mechanisms including cell-cell signaling, metabolic
      interactions, evasion of the immune response and a resident-to-pathogen switch.
      This calls for serious consideration of pathogen-microbe interactions in the host
      with respect to disease severity and progression.

PMID- 22390988
TI  - Sonography characteristics of the intra-graft thrombus: association with
      procedure success and procedure time of percutaneous transluminal angioplasty for
      thrombosed prosthetic dialysis graft.
AB  - Percutaneous transluminal angioplasty (PTA) for thrombosed dialysis graft is both
      difficult and time-consuming that may increase radiation exposure. A predictor of
      PTA success and procedure time has not been identified yet. Sonography data and
      the PTA results of 88 grafts were reviewed retrospectively. The echogenicity of
      the majority of the intra-graft thrombus and the presence/absence of thrombus
      free space in the grafts were examined. The association between the sonography
      findings and PTA procedure success and procedure time was analyzed. The
      echogenicity of the intra-graft thrombus and presence/absence of thrombus free
      space were the major determinants of procedure success and procedure time. Higher
      intra-graft echogenicity and lack of thrombus free space were associated with
      more procedure failures (p < 0.01 vs. p = 0.04) and longer procedure times (p =
      0.03 vs. p < 0.01). Thrombi from occluded dialysis grafts may differ in
      resistance to mechanical/pharmacological thrombolysis. Sonography characteristics
      of the intra-graft thrombus may help to differentiate them.

PMID- 22390989
TI  - Anterior shoulder instability: correlation between magnetic resonance
      arthrography, ultrasound arthrography and intraoperative findings.
AB  - The purpose of the present study was to determine ultrasound (US) arthrography
      diagnostic accuracy in patients with recurrent shoulder dislocation by comparing
      US arthrography and magnetic resonance arthrography (MRA) with intraoperative
      findings. Fifty-six consecutive patients with diagnosis of chronic anterior
      instability of the shoulder were evaluated for assessment of bone and soft tissue
      lesions by three radiologists. Twenty-five cases were confirmed by surgery.
      Sensitivity, specificity, inter- and intraobserver agreement were calculated.
      Ultrasound sensitivity ranged from 20% to 100% and specificity from 25% to 90%.
      MRA sensitivity ranged from 80% to 100% and specificity from 50% to 100%.
      Interobserver agreement was good for MRA (0.54-0.70) and fair for US arthrography
      (0.19-0.40). Despite a higher interobserver variability for US arthrography than
      for MRA, our results indicate that US is capable of demonstrating bone and soft
      tissue lesions related to chronic instability of the shoulder in the presence of
      intra-articular fluid.

PMID- 22390990
TI  - Characteristics of the secondary bubble cluster produced by an electrohydraulic
      shock wave lithotripter.
AB  - This study investigated the characteristics of the secondary bubble cluster
      produced by an electrohydraulic lithotripter using high-speed imaging and passive
      cavitation detection techniques. The results showed that (i) the discrepancy of
      the collapse time between near a flat rigid boundary and in a free field of the
      secondary bubble cluster was not as significant as that by the primary one; (ii)
      the secondary bubble clusters were small but in a high bubble density and
      nonuniform in distribution, and they did not expand and aggregate significantly
      near a rigid boundary; and (iii) the corresponding bubble collapse was weaker
      with few microjet formation and bubble rebound. By applying a strong suction flow
      near the electrode tip, the production of the secondary shock wave (SW) and
      induced bubble cluster could be disturbed significantly, but without influence on
      the primary ones. Consequently, stone fragmentation efficiency was reduced from
      41.2 +/- 7.1% to 32.2 +/- 3.5% after 250 shocks (p < 0.05). Altogether, these
      observations suggest that the secondary bubble cluster produced by an
      electrohydraulic lithotripter may contribute to its ability for effective stone
      fragmentation.

PMID- 22390991
TI  - Targeted delivery of bone mesenchymal stem cells by ultrasound destruction of
      microbubbles promotes kidney recovery in acute kidney injury.
AB  - The aim of the present study was to explore whether ultrasound microbubble
      destruction augments site-targeted engraftment of bone marrow mesenchymal stem
      cells (BM-MSCs) to kidney tissue and promotes recovery of the kidney in acute
      kidney injury (AKI) in rats. AKI was induced by the subcutaneous injection of
      mercuric chloride (HgCl2). Forty Sprague-Dawley (SD) rats were randomly divided
      into the following groups after the establishment of rat models of AKI (n = 10):
      (1) Model group alone (control group); (2) 1.0 W/cm2 ultrasound (US) +
      microbubble (MB) (US/MB group); (3) MSCs group; and (4) 1.0 W/cm2 US+MB + MSCs
      group (US/MB + MSCs group). The number of 4',6-diamidino-2-phenylindole (DAPI)
      labelled MSCs was evaluated by fluorescence microscopy and real-time polymerase
      chain reaction (RT-PCR) and Western blotting and histological examination were
      performed 7 days after MSCs transplantation. It was observed via fluorescence
      microscopy that the number of DAPI-labelled MSCs in the kidney for the US/MB +
      MSCs group was significantly more than the MSCs group (p < 0.05). The results
      from RT-PCR revealed that the US/MB and US/MB + MSCs groups markedly increased
      the level of inter-cellular adhesion molecule 1 (ICAM-1) messenger ribonucleic
      acid (mRNA) compared with the control group and the MSCs group (p < 0.05).
      Western blot analysis showed that the expression of hepatocyte growth factor
      (HGF) and epidermal growth factor (EGF) in the US/MB + MSCs group were markedly
      increased compared with the all other groups (p < 0.01). The extent of tubular
      necrosis and dilation was significantly milder in the US/MB + MSCs group
      (acoustic exposure conditions: 5s at 1 MHz and 1.0 W/cm2 with a 5s pause,
      totalling 60 s) than the all other groups (p < 0.05). Microbubble destruction by
      1.0 W/cm2 ultrasound can promote both the homing of BM-MSCs to kidney tissue and
      the recovery of the kidney in AKI in rats.

PMID- 22390992
TI  - Echogenic regional anaesthesia needles: a comparison study in Thiel cadavers.
AB  - Ultrasound guidance is now the standard procedure for regional nerve block in
      anesthesiology. However, ultrasonic visualisation of needle manipulation and
      guidance within tissues remains a problem. Two new echogenic needles (Pajunk and
      Braun) have been introduced to anesthesiology clinical practice but evaluation
      has been restricted to preserved animal tissue. In this study, the visibility of
      both echogenic needles was compared with a standard nonechogenic needle in a
      Thiel cadaver model. A total of 144 intramuscular injections were made in the
      upper arm in-plane and out-of-plane to the ultrasound beam at four angles (30
      degrees , 45 degrees , 60 degrees  and 75 degrees ). The visibility of the needle
      was assessed by two independent, blinded observers using a 5-point Likert ordinal
      scale. Weighted kappa for interobserver agreement was 0.77 (95% confidence
      interval [CI]: 0.68-0.86). The Pajunk echogenic needle was more visible than the
      Braun standard needle in-plane (p = 0.04), and the Braun standard and Braun
      echogenic needles out-of-plane (p = 0.02). Independent predictors of visibility
      using logistic regression were needle (p < 0.001) and plane of insertion (p =
      0.08), receiver operator characteristic (ROC) area under the curve 0.90. In
      conclusion, the Pajunk echogenic needle offers the best visibility for ultrasound
      guided regional anesthesia.

PMID- 22390993
TI  - In vivo evaluation of synthetic aperture sequential beamforming.
AB  - Ultrasound in vivo imaging using synthetic aperture sequential beamformation
      (SASB) is compared with conventional imaging in a double blinded study using side
      by-side comparisons. The objective is to evaluate if the image quality in terms
      of penetration depth, spatial resolution, contrast and unwanted artifacts is
      comparable to conventional imaging. In vivo data was acquired using a ProFocus
      ultrasound scanner (BK Medical, Herlev, Denmark) and a 192-element 3.5 MHz convex
      array transducer (Sound Technology Inc., PA, USA). Data were acquired
      interleaved, ensuring that the exact same anatomical locations were scanned.
      Eighteen volunteers were scanned abdominally resulting in 85 image sequence
      pairs. Evaluation of image quality was performed by five medical doctors. Results
      show that image quality using SASB was significantly better than conventional
      imaging (p value: <0.01). There was not a significant difference in penetration
      depth (p value: 0.55). The study supports that in vivo ultrasound imaging using
      SASB is feasible for abdominal imaging.

PMID- 22390994
TI  - The crucifixion of Jesus: review of hypothesized mechanisms of death and
      implications of shock and trauma-induced coagulopathy.
AB  - The crucifixion of Jesus is arguably the most well-known and controversial
      execution in history. Christian faithful, dating back to the time of Jesus, have
      believed that Jesus was executed by crucifixion and later returned physically to
      life again. Others have questioned whether Jesus actually died by crucifixion, at
      all. From review of medical literature, physicians have failed to agree on a
      specific mechanism of Jesus' death. A search of Medline/Pubmed was completed with
      respect to crucifixion, related topics, and proposed mechanisms of Jesus' death.
      Several hypotheses for the mechanism of Jesus' death have been presented in
      medical literature, including 1) Pulmonary embolism 2) Cardiac rupture 3)
      Suspension trauma 4) Asphyxiation 5) Fatal stab wound, and 6) Shock. Each
      proposed mechanism of Jesus' death will be reviewed. The events of Jesus'
      execution are described, as they are pertinent to development of shock. Traumatic
      shock complicated by trauma-induced coagulopathy is proposed as a contributing
      factor, and possibly the primary mechanism, of Jesus' death by crucifixion.

PMID- 22390995
TI  - Excited delirium syndrome (ExDS): treatment options and considerations.
AB  - The term Excited Delirium Syndrome (ExDS) has traditionally been used in the
      forensic literature to describe findings in a subgroup of patients with delirium
      who suffered lethal consequences from their untreated severe agitation.(1-5)
      Excited delirium syndrome, also known as agitated delirium, is generally defined
      as altered mental status and combativeness or aggressiveness. Although the exact
      signs and symptoms are difficult to define precisely, clinical findings often
      include many of the following: tolerance to significant pain, rapid breathing,
      sweating, severe agitation, elevated temperature, delirium, non-compliance or
      poor awareness to direction from police or medical personnel, lack of fatiguing,
      unusual or superhuman strength, and inappropriate clothing for the current
      environment. It has become increasingly recognized that individuals displaying
      ExDS are at high risk for sudden death, and ExDS therefore represents a true
      medical emergency. Recently the American College of Emergency Physicians (ACEP)
      published the findings of a white paper on the topic of ExDS to better find
      consensus on the issues of definition, diagnosis, and treatment.(6) In so doing,
      ACEP joined the National Association of Medical Examiners (NAME) in recognizing
      ExDS as a medical condition. For both paramedics and physicians, the difficulty
      in diagnosing the underlying cause of ExDS in an individual patient is that the
      presenting clinical signs and symptoms of ExDS can be produced by a wide variety
      of clinical disease processes. For example, agitation, combativeness, and altered
      mental status can be produced by hypoglycemia, thyroid storm, certain kinds of
      seizures, and these conditions can be difficult to distinguish from those
      produced by cocaine or methamphetamine intoxication.(7) Prehospital personnel are
      generally not expected to differentiate between the multiple possible causes of
      the patient's presentation, but rather simply to recognize that the patient has a
      medical emergency and initiate appropriate stabilizing treatment. ExDS patients
      will generally require transfer to an emergency department (ED) for further
      management, evaluation, and definitive care. In this paper, we present a typical
      ExDS case and then review existing literature for current treatment options.

PMID- 22390996
TI  - Phenazepam: the drug that came in from the cold.
AB  - In the past few years there has been concern in Western Europe and in the US
      about the rise in abuse of phenazepam, a benzodiazepine that was originally
      developed in the USSR in the mid- to late 1970s.(1-4) Although phenazepam is one
      of the most widely prescribed benzodiazepines in Russia and other commonwealth of
      independent state (CIS) countries, it has not been licensed elsewhere in the
      world. Due to very limited licensed geographical distribution, there is very
      little peer-reviewed literature that is not written in Russian. In this article,
      we review the current state of what is currently known about phenazepam. This
      information on phenazepam and how it can be detected in biological specimens
      should assist the forensic community in identifying phenazepam in routine
      toxicology screening and interpreting any phenazepam concentrations that are
      obtained.

PMID- 22390997
TI  - CT based volume measurement and estimation in cases of pericardial effusion.
AB  - The measurement of fluid volumes in cases of pericardial effusion is a necessary
      procedure during autopsy. With the increased use of virtual autopsy methods in
      forensics, the need for a quick volume measurement method on computed tomography
      (CT) data arises, especially since methods such as CT angiography can potentially
      alter the fluid content in the pericardium. We retrospectively selected 15 cases
      with hemopericardium, which underwent post-mortem imaging and autopsy. Based on
      CT data, the pericardial blood volume was estimated using segmentation techniques
      and downsampling of CT datasets. Additionally, a variety of measures (distances,
      areas and 3D approximations of the effusion) were examined to find a quick and
      easy way of estimating the effusion volume. Segmentation of CT images as shown in
      the present study is a feasible method to measure the pericardial fluid amount
      accurately. Downsampling of a dataset significantly increases the speed of
      segmentation without losing too much accuracy. Some of the other methods examined
      might be used to quickly estimate the severity of the effusion volumes.

PMID- 22390998
TI  - Reconstruction of femur length from its fragments in South Indian males.
AB  - Stature is one of the essential parameters in the establishment of identity of an
      individual. It is well documented from the previous studies that intact femur has
      the highest correlation with stature and as such widely used in the regression
      equation derivations. However, the femur is not always recovered intact in
      forensic cases, thereby rendering the equations derived from the whole bone
      inappropriate for analysis. This has necessitated the derivation of regression
      equations for estimating the length of femur, from the fragments of femur. The
      calculated maximum femoral length can then be used to estimate the stature of the
      individual by the regression equations, tables or the multiplication factors
      already established by the various studies. Seven variables were measured in a
      sample of 60 male femora. All the measurements showed positive degree of
      correlation. Regression equations for the estimation of maximum length of femur
      were derived. It is therefore stated that in the absence of intact femur,
      regression equations derived from the present study can provide a reliable
      estimate of maximum length of femur in South Indian males and thereby the adult
      stature.

PMID- 22390999
TI  - Metric method for sex determination based on the 12th thoracic vertebra in
      contemporary north-easterners in China.
AB  - Many studies have shown that discriminant function equations, used in the
      determination of sex from skeletons, are population specific. The aim of the
      present research was to develop discriminant function equations for sex
      determination using the 12th thoracic vertebra (T12) in a contemporary northeast
      Chinese sample and to investigate whether the differences of the T12 between
      males and females consist more in shape than in size. Thirty linear measurements
      were obtained from 141 three-dimensional reconstructed T12 models (78 males and
      63 females), and then 112 ratios were calculated by using the thirty linear
      measurements. Of the 30 linear measurements, 28 were sexually dimorphic, and
      their univariate discriminant function equations predicted sex with 56.4-90.1%
      accuracies. Of the 112 ratios, 62 were sexually dimorphic, with accuracies
      ranging from 56.7% to 73.8%. Using stepwise method of discriminant function
      analysis, four variables predicted sex with 94.2% accuracy. It is concluded that
      the T12 vertebra of the north-easterners in China is useful for sex
      determination, and the size of the T12 vertebra contributes more than the shape
      in the differences of the T12 vertebra between males and females.

PMID- 22391000
TI  - Focal traumatic brain stem injury is a rare type of head injury resulting from
      assault: a forensic neuropathological study.
AB  - INTRODUCTION: Brainstem haemorrhage is common in cases of head injury when it is
      associated with space-occupying lesion and increases in the intracranial pressure
      (duret haemorrhage), in cases of diffuse axonal injury (in dorso-lateral
      quadrant) and diffuses vascular injury (in the periventricular tissue). However
      focal traumatic brainstem injury is rare. MATERIAL AND METHOD: We identified 12
      cases of focal traumatic brainstem injury from review of 319 case of head injury.
      The head trauma had been caused by different mechanisms of complex fall from
      height and assault. 10/12 are associated with skull fracture, 11/12 with contre
      coup contusions in the frontal and temporal lobes, 5/12 direct contusions to
      cerebellum, 5/12 haemorrhage in corpus callosum and 2/11 have gliding contusions.
      None of the cases had pathological evidence of increase in the intracranial
      pressure. The bleeding in the pons was at the edge in 2/12 and cross the section
      in 10/12. The majority of patients were unconscious immediately after the
      incident (10/12) and 9/12 died within one day. CONCLUSION: Focal traumatic
      brainstem injury occurs most likely due to direct impact at the back of the head
      or stretching forces affecting the brainstem in cases of complex fall from height
      and after assault, particularly those associated with kicks. It is a serious and
      commonly fatal brain damage, which needed to be differentiated from other causes
      of brainstem haemorrhages.

PMID- 22391001
TI  - Racial variation on articular surface of talus (astragalus) in North Indian
      population.
AB  - Articular morphology, especially of the lower limb, can be modified by various
      stresses on bone like adoption of bipedal gait and erect posture resulting in
      variations of the skeleton. Effects of variations in posture like squatting,
      which are a part of lifestyle of certain populations, were studied on 147 tali of
      North Indian population and examined for differences with those from other
      geographic regions. The modifications were classified into nine types. The
      lateral squatting facet was the most frequently found variation (65.9%), the
      medial, combined and continuous squatting facets being 8.2%, 2.04% and 4.1%,
      respectively. Lateral (32.7%), medial (27.2%) and continuous (4.7%), trochlear
      extensions, and extensions of medial (39.4%) and lateral (12.9%) articular facets
      were also observed in the population studied. The findings of the present study
      were important markers which could help in determining the race of unidentified
      bones.

PMID- 22391002
TI  - The assessment of lethal propeller strike injuries in sea mammals.
AB  - Assessment of injuries in marine mammals may be required to help authorities
      determine whether human activity was involved. Three cases of marine animal
      deaths involving propeller blade strikes are reported to demonstrate
      characteristic features of such cases and diagnostic difficulties that may occur.
      Case 1: A juvenile New Zealand fur seal (Arctocephalus forsteri) suffered two
      parallel linear incised wounds of the flank and died following small intestinal
      herniation. Case 2: An Indo-Pacific bottlenose dolphin neonate (Tursiops aduncus)
      died from a deeply incised wound of the left side of the head with shattering of
      the skull and laceration of the underlying brain.Case 3: An adult female Indo
      Pacific bottlenose dolphin (T. aduncus) died from two parallel chop wounds to the
      torso with opening of the thoracic and abdominal cavities with fractures of the
      ribs and vertebrae. Given that some animals may recover, and that the carcasses
      of those that are killed may simply not be found or reported, it is impossible to
      provide an estimate of the incidence of this type of injury amongst wild sea
      mammals. In cases that do come to forensic attention accurate evaluation of the
      type of injury may potentially have great medicolegal significance. Post-mortem
      putrefaction and post-mortem feeding by other sea animals may complicate
      assessments.

PMID- 22391003
TI  - Sex estimation from foramen magnum dimensions in an Indian population.
AB  - Identification of skeletal remains is vital in forensic investigations. The need
      for methods to estimate sex from cranial fragments becomes apparent when only a
      part of skull is brought for identification. The present research is an attempt
      to study the sexual dimorphism of the anteroposterior diameter, transverse
      diameter and area of foramen magnum in a population of costal Karnataka region
      using statistical considerations. Ninety adult dry skulls of known sex (50 male
      and 40 female) were included in the study. Morphometric analysis of foramen
      magnum was conducted using vernier calipers and the area of foramen magnum was
      calculated. The anteroposterior diameter, transverse diameter and area of foramen
      magnum are found to be significantly larger in males than females. Binary
      Logistic Regression (BLR) analysis was performed to derive models for estimation
      of sex from the different measurements of foramen magnum and Receiver Operating
      Characteristic (ROC) curve was drawn for the predicted probabilities obtained
      from BLR analysis. The predictability of foramen magnum measurements in sexing of
      crania was 65.4% for transverse diameter and 86.5% for the anteroposterior
      diameter. For the area of foramen magnum that was calculated using the formula
      derived by Radinsky and Teixeria, the predicted probabilities were observed to be
      81.6% and 82.2% respectively. When anteroposterior and transverse diameter were
      used together in BLR analysis the predictability of sex increased to 88%.
      However, considering the overlapping in the male and female values for the
      foramen magnum measurements it is suggested that its application in sex
      estimation should be restricted to cases where only a fragment of base of the
      skull is brought for examination. In such cases, the anteroposterior diameter and
      area of the foramen magnum can be employed as better tools for sexing the skulls
      than the transverse diameter of the foramen magnum.

PMID- 22391004
TI  - Assessment of the responsibility between a road traffic accident and medical
      defects after the traffic accident injury of knee joint.
AB  - A 48-year-old Chinese woman was hit by a car in a road traffic accident. Local
      county hospital considered that her right knee was injured, but didn't find any
      sign of fracture from X-ray imaging. Then the hospital gave diagnosis of soft
      tissue contusion and the patient started to exercise with burden 21 days after
      her right lower limb was fixed by plaster slab. Four months later, she had to go
      back to the county hospital for recheck due to persistent pain on her right knee.
      Then, the right tibia outer plateau fracture was found. The patient rejected the
      advice of open reduction and internal fixation of right tibia plateau fracture.
      Instead, she accepted the unicompartmental knee arthroplasty in a hospital
      affiliated to a medical college. The patient felt the knee pain alleviated after
      surgery However, the joint dysfunction was aggravated even more. The patient used
      the legal procedure for personal compensation. Both driver and the insurance
      company disputed that the final consequence of the injured knee was due to not
      only the traffic accident, but also poor medical practice involved. Therefore the
      court consigned us to make judicial judgment of expertise. After investigation,
      we found the earliest X-ray graph after the accident had shown the fracture of
      right tibia outer plateau and right knee valgum, with articular surface
      involvement, and the traffic accident was considered as the primary cause of
      sequelae. At the same time, the county hospital missed the diagnosis of fracture,
      and led to insufficient fixation of right lower limb, which was not good for
      rehabilitation from fracture and joint injury. This was the secondary cause of
      sequelae. Additionally, instead of the standard therapy, the affiliated hospital
      of medical college made the unicompartmental knee arthroplasty four months later,
      which also had a little defect. It was the minor reason for the result.

PMID- 22391005
TI  - Child starvation and neglect: a report of two fatal cases.
AB  - Fatal starvation is a rare cause of death in industrialised countries. In such
      cases, investigation of death is never an easy task for forensic pathologists who
      need to couple autopsy findings with full investigation of the crime scene and
      family record to establish if death results from deliberate neglect, maltreatment
      and withholding of food. The present article describes two cases of death caused
      by child neglect. The first case involved a 16-month-old female who died from
      starvation with dehydration as a contributing factor. In the second case a 7-year
      old girl died from ultimate aspiration of stomach contents that had been vomited
      during the child's last meal because of the fecal concretions blocking the
      intestinal passage. In both cases macroscopic and histological findings revealed
      severe chronic malnutrition; crime scene investigations confirmed stories of
      child maltreatment and neglect.

PMID- 22391006
TI  - Differential diagnosis between cranial fractures of traumatic origin and
      explosion fractures in burned cadavers.
AB  - Interpreting the damages on a cadaver which has been exposed to the action of
      fire is a challenge for the forensic pathologist. The finding of a burned body
      gives in fact the opportunity to make a series of inquiries which deal with the
      whole medical-legal practice. In our case, the victim has been hit over the head
      with a blunt object and has been then carbonized. The medical-legal problems
      implied lie in the definition of the exact manner and cause of death, and
      therefore in the analysis of vital, perimortal and postmortal injuries, as to
      formulate a differential diagnosis between the former traumatic originated and
      the latter caused by combustion.

PMID- 22391007
TI  - A challenging injury interpretation: could this be a stab wound?
AB  - Forensic practitioner should exercise caution in the forensic interpretation of
      suspicious wounds at death scenes, at least until there is an opportunity to
      fully explore the wound and its relationship to underlying structures and bony
      landmarks. This is especially so in cases of apparent suicide. A case is
      presented which not only illustrates the challenges which may face the examiner
      at a death scene in injury interpretation, but also, where there remains a
      lingering doubt that the autopsy did not address all of the concerns expressed by
      both scenes of crime scientific officers and the forensic medical examiner.

PMID- 22391008
TI  - Hb level in relation to vitamin D status in healthy infants and toddlers.
AB  - OBJECTIVE: To assess the presence of an association between vitamin D deficiency
      and anaemia in Jordanian infants and toddlers, in whom both vitamin D deficiency
      and anaemia have previously been proved to be common separately. DESIGN: Cross
      sectional prospective study. SETTING: Department of Paediatrics, Princess Rahma
      Teaching Hospital, Jordan. SUBJECTS: Healthy infants and children aged 6-36
      months who were seen for primary care. RESULTS: Out of 203 infants and toddlers
      included in the study, the anaemia prevalence was 40.4 %. The prevalence of
      anaemia among infants (n 110) was 51.8 %, whereas it was 26.9 % among toddlers (n
      93). No association between vitamin D status and anaemia was found. CONCLUSIONS:
      Vitamin D deficiency is not a risk for anaemia in infants and toddlers.

PMID- 22391009
TI  - The minimum temperature for budburst in Betula depends on the state of dormancy.
AB  - Vegis has put forward the theory that the range of growth-promoting temperatures
      changes during the induction and the release of dormancy. We have tested the
      response of buds of Betula pubescens Ehrh. and B. pendula Roth. on temperature
      during the induction and release of dormancy. Betula seedlings were exposed to
      dormancy-inducing high-temperature and short-day conditions and subsequently to
      dormancy-releasing chilling conditions in darkness. To monitor the dormancy
      status of the seedlings, subsets of them were transferred to five forcing
      temperatures and their budburst was observed. The results show that the
      expression of dormancy was temperature dependent, so that the minimum temperature
      for 100% budburst rose during the induction and dropped during the release of
      dormancy. These responses may explain previous contradictions between
      experimental and modelling studies, but that needs to be verified with more
      extensive experiments, some of which are identified in this study. The results
      provide further evidence for the concept of gradual change in bud dormancy. They
      also suggest that global change studies modelling budburst phenology should
      address the changing expression of bud dormancy.

PMID- 22391010
TI  - Novel Prunus rootstock somaclonal variants with divergent ability to tolerate
      waterlogging.
AB  - Plants require access to free water for nutrient uptake, but excess water
      surrounding the roots can be injurious or even lethal because it blocks the
      transfer of free oxygen between the soil and the atmosphere. Genetic improvement
      efforts in this study were focused on the increased tolerance in roots to
      waterlogging. Among a pool of clones generated in vitro from leaf explants of
      rootstock Mr.S.2/5 of Prunus cerasifera L., the S.4 clone was flood tolerant
      whereas the S.1 clone was sensitive. The S.4 clone formed adventitious roots on
      exposure to flooding. Moreover, the chlorophyll content and mitochondrial
      activity in the leaf and root, soluble sugar content, alcohol dehydrogenase
      activity and ethylene content were different between the clones. The sorbitol
      transporter gene (SOT1) was up-regulated during hypoxia, the alcohol
      dehydrogenase genes (ADH1 and ADH3) were up-regulated in the leaves and down
      regulated in the roots of the S.4 clone during hypoxia, and the 1
      aminocyclopropane-1-oxidase gene (ACO1) was up-regulated in the leaves and roots
      of the S.4 clone during hypoxia and down-regulated in the wild-type roots. In
      addition, in the S.4 root, hypoxia induced significant down-regulation of a
      glycosyltransferase-like gene (GTL), which has a yet-undefined role. Although the
      relevant variation in the S.4 genome has yet to be determined, genetic alteration
      clearly conferred a flooding-tolerant phenotype. The isolation of novel
      somaclonals with the same genomic background but with divergent tolerance to
      flooding may offer new insights in the elucidation of the genetic machinery of
      resistance to flooding and aid in the selection of new Prunus rootstocks to be
      used in various adverse environments.

PMID- 22391011
TI  - Theoretical dosimetry estimations for radioisotopes produced by proton-induced
      reactions on natural and enriched molybdenum targets.
AB  - This study presents a summary of the dosimetry calculations performed for three
      technetium agents most commonly used in nuclear medicine diagnostic studies,
      namely sestamibiTM, phosphonates and pertechnetate, labeled with cyclotron
      produced technetium. Calculated patient doses were compared to those that would
      be delivered by the same radiotracers labeled with technetium obtained from a
      generator produced in a reactor. The main difference is that technetium from a
      generator is pure, i.e. contains only (99m)Tc and its decay product (99g)Tc,
      while in a cyclotron a large number of other stable and radioactive isotopes are
      created. In our calculations only technetium radioisotopes (ground and isomeric
      states) were considered as they will be included in the radiotracer labeling
      process and will contribute to the patient dose. Other elements should be removed
      by chemical purification. These dose estimates are based on our theoretical
      calculations of the proton-induced reaction cross sections and radioisotope
      production yields. Thick targets of enriched (three different compositions) and
      natural molybdenum, and three initial beam energies (16, 19 and 24 MeV) were
      considered for irradiation times of 3, 6 and 12 h with a beam current of 200 uA.
      The doses were calculated for injection times corresponding to 0, 2, 8, 12 and 24
      h after the end of beam.

PMID- 22391013
TI  - Identification of brain regions responsible for Alzheimer's disease using a Self
      adaptive Resource Allocation Network.
AB  - In this paper, we present a novel approach for the identification of brain
      regions responsible for Alzheimer's disease using the Magnetic Resonance (MR)
      images. The approach incorporates the recently developed Self-adaptive Resource
      Allocation Network (SRAN) for Alzheimer's disease classification using voxel
      based morphometric features of MR images. SRAN classifier uses a sequential
      learning algorithm, employing self-adaptive thresholds to select the appropriate
      training samples and discard redundant samples to prevent over-training. These
      selected training samples are then used to evolve the network architecture
      efficiently. Since, the number of features extracted from the MR images is large,
      a feature selection scheme (to reduce the number of features needed) using an
      Integer-Coded Genetic Algorithm (ICGA) in conjunction with the SRAN classifier
      (referred to here as the ICGA-SRAN classifier) have been developed. In this
      study, different healthy/Alzheimer's disease patient's MR images from the Open
      Access Series of Imaging Studies data set have been used for the performance
      evaluation of the proposed ICGA-SRAN classifier. We have also compared the
      results of the ICGA-SRAN classifier with the well-known Support Vector Machine
      (SVM) and Extreme Learning Machine (ELM) classifiers. The study results clearly
      show that the ICGA-SRAN classifier produces a better generalization performance
      with a smaller number of features, lower misclassification rate and a compact
      network. The ICGA-SRAN selected features clearly indicate that the variations in
      the gray matter volume in the parahippocampal gyrus and amygdala brain regions
      may be good indicators of the onset of Alzheimer's disease in normal persons.

PMID- 22391012
TI  - Starvation, detoxification, and multidrug resistance in cancer therapy.
AB  - The selection of chemotherapy drugs is based on the cytotoxicity to specific
      tumor cell types and the relatively low toxicity to normal cells and tissues.
      However, the toxicity to normal cells poses a major clinical challenge,
      particularly when malignant cells have acquired resistance to chemotherapy. This
      drug resistance of cancer cells results from multiple factors including
      individual variation, genetic heterogeneity within a tumor, and cellular
      evolution. Much progress in the understanding of tumor cell resistance has been
      made in the past 35 years, owing to milestone discoveries such as the
      identification and characterization of ABC transporters. Nonetheless, the
      complexity of the genetic and epigenetic rewiring of cancer cells makes drug
      resistance an equally complex phenomenon that is difficult to overcome. In this
      review, we discuss how the remarkable changes in the levels of glucose, IGF-I,
      IGFBP-1 and in other proteins caused by fasting have the potential to improve the
      efficacy of chemotherapy against tumors by protecting normal cells and tissues
      and possibly by diminishing multidrug resistance in malignant cells.

PMID- 22391014
TI  - Androgen deprivation therapy for prostate cancer: implications for
      cardiometabolic clinical care.
AB  - Prostate cancer (PCa) is the most common malignancy in men. Androgen deprivation
      therapy (ADT) plays an important role in the management of locally advanced and
      metastatic PCa. Its use in combination with external beam radiation and as an
      adjuvant therapy has resulted in improved survival in a subset of patients with
      locally advanced disease. In men with metastatic disease, ADT results in
      improvement in pain and overall quality of life. In addition to these two
      clinical settings where ADT has proven benefits, it is also being increasingly
      used in patients experiencing biochemical recurrence and those with early stage
      localized disease, even though no survival advantage has been demonstrated. ADT
      has significant adverse effects such as sexual dysfunction, decreased lean mass,
      increased fat mass, decreased quality of life, anemia, and osteoporosis.
      Recently, insulin resistance, diabetes, and metabolic syndrome have emerged as
      complications of ADT. Some data also suggests that ADT might be responsible for
      incident cardiovascular disease. Since the majority of men with PCa die of
      conditions other than their malignancy, recognition and management of these
      adverse effects is important. This paper serves as a focused review of recent
      studies examining the metabolic abnormalities and cardiovascular disease related
      to ADT.

PMID- 22391016
TI  - A systematic review of retention of adult advanced life support knowledge and
      skills in healthcare providers.
AB  - OBJECTIVE: Advanced life support (ALS) guidelines are widely adopted for
      healthcare provider training with recommendations for retraining every two years
      or longer. This systematic review studies the retention of adult ALS knowledge
      and skills following completion of an ALS course in healthcare providers.
      METHODS: We retrieved original articles using Medline, CINAHL, Cochrane Library,
      and PubMed, and reviewed reference citations to identify additional studies. We
      extracted data from included articles using a structured approach and organized
      outcomes by evaluation method, and knowledge and skills retention. RESULTS: Among
      336 articles retrieved, 11 papers were included. Most studies used multiple
      choice questionnaires to evaluate knowledge retention and cardiac arrest
      simulation or other skills tests to evaluate skills retention. All studies
      reported variable rates of knowledge or skills deterioration over time, from 6
      weeks to 2 years after training. Two studies noted retention of knowledge at 18
      months and up to 2 years, and one reported skills retention at 3 months. Clinical
      experience, either prior to or after the courses, has a positive impact on
      retention of knowledge and skills. CONCLUSION: There is a lack of large well
      designed studies examining the retention of adult ALS knowledge and skills in
      healthcare providers. The available evidence suggests that ALS knowledge and
      skills decay by 6 months to 1 year after training and that skills decay faster
      than knowledge. Additional studies are needed to help provide evidence-based
      recommendations for assessment of current knowledge and skills and need for
      refresher training to maximize maintenance of ALS competency.

PMID- 22391017
TI  - Effects of local climate and hydrological conditions on the thermal regime of a
      reservoir at Tropic of Cancer, in southern China.
AB  - Thermal regime is strongly associated with hydrodynamics in water, and it plays
      an important role in the dynamics of water quality and ecosystem succession of
      stratified reservoirs. Changes in both climate and hydrological conditions can
      modify thermal regimes. Liuxihe Reservoir (23 degrees 45'50"N; 113 degrees
      46'52"E) is a large, stratified and deep reservoir in Guangdong Province, located
      at the Tropic of Cancer of southern China. The reservoir is a warm monomictic
      water body with a long period of summer stratification and a short period of
      mixing in winter. The vertical distribution of suspended particulate material and
      nutrients are influenced strongly by the thermal structure and the associated
      flow fields. The hypolimnion becomes anoxic in the stratified period, increasing
      the release of nutrients from the bottom sediments. Fifty-one years of climate
      and reservoir operational observations are used here to show the marked changes
      in local climate and reservoir operational schemes. The data show increasing air
      temperature and more violent oscillations in inflow volumes in the last decade,
      while the inter-annual water level fluctuations tend to be more moderate. To
      quantify the effects of changes in climate and hydrological conditions on thermal
      structure, we used a numerical simulation model to create scenarios incorporating
      different air temperatures, inflow volumes, and water levels. The simulations
      indicate that water column stability, the duration of the mixing period, and
      surface and outflow temperatures are influenced by both natural factors and by
      anthropogenic factors such as climate change and reservoir operation schemes.
      Under continuous warming and more stable storage in recent years, the simulations
      indicate greater water column stability and increased duration of stratification,
      while irregular large discharge events may reduce stability and lead to early
      mixing in autumn. Our results strongly suggest that more attention should be
      focused on water quality in years of extreme climate variation and hydrological
      conditions, and selective withdrawal of deep water may provide an efficient means
      to reduce internal loading in warm years.

PMID- 22391018
TI  - Completeness of metabolic disease recordings in Nordic national databases for
      dairy cows.
AB  - The four Nordic countries Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE)
      all have national databases where diagnostic events in dairy cows are recorded.
      Comparing and looking at differences in disease occurrence between countries may
      give information on factors that influence disease occurrence, optimal diseases
      control and treatment strategies. For such comparisons to be valid, the data in
      these databases should be standardised and of good quality. The objective of the
      study presented here was to assess the quality of metabolic disease recordings,
      primarily milk fever and ketosis, in four Nordic national databases. Completeness
      of recording figures of database registrations at two different levels was chosen
      as a measure of data quality. Firstly, completeness of recording of all disease
      events on a farm regardless of veterinary involvement, called 'Farmer observed
      completeness', was determined. Secondly, completeness of recording of veterinary
      treated disease events only, called 'Veterinary treated completeness', was
      determined. To collect data for calculating these completeness levels a simple
      random sample of herds was obtained in each country. Farmers who were willing to
      participate, recorded for 4 months in 2008, on a purpose made registration form,
      any observed illness in cows, regardless of veterinary involvement. The number of
      participating herds was 105, 167, 179 and 129 in DK, FI, NO and SE respectively.
      In total these herds registered 247, 248, 177 and 218 metabolic events for
      analysis in DK, FI, NO and SE, respectively. Data from national databases were
      subsequently extracted, and the two sources of data were matched to find the
      proportion, or completeness, of diagnostic events registered by farmers that also
      existed in national databases. Matching was done using a common diagnostic code
      system and allowed for a discrepancy of 7 days for registered date of the event.
      For milk fever, the Farmer observed completeness was 77%, 67%, 79% and 79%, and
      for Veterinary treated completeness 88%, 71%, 80% and 82%, in DK, FI, NO and SE,
      respectively. For ketosis, the Farmer observed completeness was 77%, 55%, 70% and
      46%, and for Veterinary treated completeness 84%, 75%, 79% and 56%, in DK, FI, NO
      and SE, respectively. The differences observed in some of these completeness
      figures indicate that metabolic disease frequency measures when calculated from
      these four national databases do not accurately reflect the true difference in
      metabolic disease occurrence in dairy cows between countries. Further
      standardisation of disease registrations is necessary for valid between-country
      assessments.

PMID- 22391019
TI  - A semi-parametric model for lactation curves: development and application.
AB  - We propose a semi-parametric model for lactation curves that, along with stage of
      lactation, accounts for day of the year at milk recording and stage of gestation.
      Lactation is described as having 3 different phases defined by 2 change points of
      which the second is a function of gestation stage. Season of milk recording is
      modelled using cosine and sine functions. As an application, the model is used to
      estimate the association between intramammary infections (IMI) dynamics as
      measured by somatic cell count (SCC) over the dry period and the shape of the
      lactation curve. Milk recording data collected in 2128 herds from England and
      Wales between 2004 and 2007 were used in the analysis. From a random sample of
      1000 of these herds, smoothed milk production was used to test the behaviour of
      the model and estimate model parameters. The first change point was set at 60
      days in milk. The second change point was set at 100 days of gestation or 200
      days in milk when the latter was not available. Using data from the 1128
      remaining herds, multilevel models were then used to model individual test-day
      milk production within lactations within herds. Average milk production at 60
      days in milk for cows of parities 1, 2, 3 and greater than 3 were 26.9 kg, 31.6
      kg, 34.4 kg and 34.7 kg respectively and, after this stage, decreases in milk
      production per 100 days milk of lactation were 3.1 kg, 5.1 kg, 6.3 kg and 6.7 kg
      respectively. Compared to cows that had an SCC below 200,000 cells/mL on both the
      last milk recording in a lactation and the first milk recording in the following
      lactation, cows that had an SCC greater than 200,000 cells/mL on their first milk
      recording after calving had an estimated loss of milk production of between 216
      and 518 kg depending on parity. These estimates demonstrate the impact of the
      dynamics of SCC during the dry period on milk production during the following
      lactation.

PMID- 22391020
TI  - Predictors of differences in the perception of antimicrobial resistance risk in
      the treatment of sick, at-risk, and high-risk feedlot cattle.
AB  - Concerns exist that some uses of antimicrobials in cattle may lead to the
      emergence, proliferation, dissemination and persistence of resistant pathogenic
      bacteria in animal agriculture, which in turn can infect humans via the food
      supply. The degree of perceived risk varies with the clinical indication for
      which the antimicrobial in question is used. In this study, four uses of
      antimicrobials are considered, including in acutely sick, chronically sick, at
      risk, and high-risk cattle, contrasting the degree of risk among these uses.
      Using a random sample of 103 feedlot cattle veterinarians and variables drawn
      from the theory of planned behavior, we predict differences in risk perception by
      clinical indication with differences in perceived efficacy of antimicrobials,
      social pressures to use antimicrobials, and moral obligations to use
      antimicrobials. In most models, veterinarians who perceived that others in the
      feedlot industry (i.e., other feedlot veterinarians, nutritionists, feedlot
      clients, and retained owners of cattle) were more likely to expect them to use
      antimicrobials in one situation versus another, the less likely those
      veterinarians perceived the risk of antimicrobial risk to be greater in the
      former versus the latter situation. Only two of these contrasts contained
      influences outside the immediate feedlot relationships. This exception involves
      the 'downstream' public: meat packers, retailers, and consumers. Veterinarians
      who believe that using antimicrobials for acutely sick cattle is more beneficial
      than using antimicrobials for chronically sick cattle were more likely to believe
      that antimicrobial resistance was a less probable outcome in acutely sick cattle
      than in chronically sick cattle.

PMID- 22391021
TI  - Evaluation of two cocktails containing ESAT-6, CFP-10 and Rv-3615c in the
      intradermal test and the interferon-gamma assay for diagnosis of bovine
      tuberculosis.
AB  - The intradermal tuberculin tests and the interferon-gamma (IFN-gamma) assay are
      the principal tests used worldwide for the ante-mortem diagnosis of bovine
      tuberculosis. The conventional reagent currently in use in these tests is
      purified protein derivative (PPD) tuberculin obtained from Mycobacterium bovis
      culture. The components of PPD are poorly characterized and difficult to
      standardize. To overcome this issue, antigens specific to the Mycobacterium
      tuberculosis complex are being studied. Here we have assessed the biological
      potency of ESAT-6, CFP-10 and Rv-3615c presented as peptide or recombinant
      protein cocktails in comparison with the standard bovine PPD used routinely in
      Spanish eradication campaigns. The study was performed in cattle (n=23) from a
      herd with natural M. bovis infection. Animals were simultaneously injected with
      PPD and the peptide and protein cocktails. The percentages of cattle reacting
      positively to single intradermal test were 60.9% (bovine PPD), 47.8% (peptide
      cocktail) and 60.9% (protein cocktail), with no significant difference between
      the actual skin fold thickness increases (p>0.05). The IFN-gamma assay detected
      60.9% of animals when stimulation was performed with bovine PPD, but decreased to
      52.2% when stimulation was performed with the peptide cocktail and to 47.8% when
      stimulation was performed with the protein cocktail. However, no significant
      differences were found between IFN-gamma responder frequencies (p>0.05). These
      results show a potential use of these defined reagents for in vivo tuberculosis
      diagnosis.

PMID- 22391022
TI  - The use of PEGylated liposomes to prolong the circulation lifetime of salvianolic
      acid B.
AB  - The clinical application of salvianolic acid B (Sal B), a potential therapeutic
      agent for cardiovascular diseases isolated from Salvia miltiorrhiza, is greatly
      restricted by its short half-life and low bioavailability. To improve therapeutic
      effects and prolong the systemic circulation time of Sal B, liposomes, composed
      of soybean phosphatidylcholine and cholesterol were prepared by reverse-phase
      evaporation method. In addition, polyethylene glycol 2000
      disteroylphosphoethanolamine (PEG-DSPE 2000) was included to give steric barrier
      to liposomes. A central composite design was employed to optimize liposomal
      formulation with high encapsulation efficiency and small particle size.
      Physicochemical characteristics such as particle size, zeta potential,
      encapsulation efficiency and in vitro release were investigated. In vivo
      pharmacokinetic properties of Sal B in beagle dogs and the effect of PEG on the
      blood circulation time of Sal B-loaded liposomes were also evaluated. An
      optimized formulation with encapsulation efficiency of 73.68% and mean particle
      size of 136.6nm were developed. Encapsulation of Sal B into conventional and
      PEGylated liposomes could prolong the half-life of Sal B by 5.8- and 17.5-fold
      and enhance the AUC(0-t) of Sal B by 6.7- and 13.3-fold compared with free Sal B,
      respectively. Therefore, the use of PEGylated liposomes could prolong the
      circulation time in blood and longevity effect of liposomes on Sal B was
      increased by PEG.

PMID- 22391023
TI  - Transdermal microemulsion drug delivery system for impairing male reproductive
      toxicity and enhancing efficacy of Tripterygium Wilfordii Hook f.
AB  - The present study is trying to produce a transdermal microemulsion drug delivery
      system (TMDDS) for Tripterygium Wilfordii Hook f. (TWHF) and attempting to solve
      male reproductive toxicity problem of TWHF. The formulation was optimized by the
      central composite design with response surface methodology and was decided as 12%
      oleic acid, 19.7% Labrasol S, 19.7% ethanol and 19.7% Pharmasolve, and 29% water.
      TMDDS for TWHF had stronger transdermal ability than free TWHF, and TWHF
      microemulsion significantly inhibited the adjuvant-induced arthritis and at the
      same time, had preferable anti-inflammatory effect with the long-time
      administration. Various pharmacodynamics parameters proved that TWHF
      microemulsion can reduce the male reproductive toxicity and hepatotoxicity of
      rats. All these suggested that TMDDS could be a suitable delivery system for
      TWHF.

PMID- 22391024
TI  - A cytotoxic triterpenoid saponin from under-ground parts of Gypsophila pilulifera
      Boiss.& Heldr.
AB  - A cytotoxic triterpenoid saponin was isolated from the under-ground parts of
      Gypsophila pilulifera Boiss.& Heldr. (Caryophyllaceae) naturally grow in the
      southwestern region of the Turkey. The structures of saponin was elucidated as 3
      O-beta-D-galactopyranosyl-(1->2)-[beta-D-xylopyranosyl-(1->3)]-beta-D
      glucuronopyranosyl quillaic acid 28-O-beta-D-glucopyranosyl-(1->3)-[beta-d
      xylopyranosyl-(1->4]-alpha-l-rhamnopyranosyl-(1->2)-beta-D-fucopyranosyl ester on
      the basis of extensive spectral analysis and chemical evidence. The separated
      triterpenoid saponin was isolated from Gypsophila pilulifera for the first time.
      The saponin compound displayed significant cytotoxicity against A549 cell line
      with IC(50) values >16MUM.

PMID- 22391025
TI  - Epigenetic and antioxidant effects of dietary isothiocyanates and selenium:
      potential implications for cancer chemoprevention.
AB  - There is evidence from epidemiological studies suggesting that increased
      consumption of cruciferous vegetables may protect against specific cancers more
      effectively than total fruit and vegetable intake. These beneficial effects are
      attributed to the glucosinolate breakdown products, isothiocyanates (ITC).
      Similarly, selenium (Se) consumption has also been inversely associated with
      cancer risk and as an integral part of many selenoproteins may influence multiple
      pathways in the development of cancer. This paper will briefly review the current
      state of knowledge concerning the effect of Se and ITC in cancer development with
      a particular emphasis on its antioxidant properties, and will also address
      whether alterations in DNA methylation may be a potential mechanism whereby these
      dietary constituents protect against the carcinogenic process. Furthermore, we
      will discuss the advantages of combining ITC and Se to benefit from their
      complementary mechanisms of action to potentially protect against the alterations
      leading to neoplasia. Based on this review it may be concluded that an
      understanding of the impact of ITC and Se on aberrant DNA methylation in relation
      to factors modulating gene-specific and global methylation patterns, in addition
      to the effect of these food constituents as modulators of key selenoenzymes, such
      as gastrointestinal glutathione peroxidase-2 (GPx2) and thioredoxin reductase-1
      (TrxR1), may provide insights into the potential synergy among various components
      of a plant-based diet that may counteract the genetic and epigenetic alterations
      that initiate and sustain neoplasia.

PMID- 22391026
TI  - Performance evaluation of Siemens ADVIA Centaur enhanced estradiol assay and a
      split sample comparison with liquid chromatography-tandem mass spectrometry.
AB  - OBJECTIVES: The objective of this study was to evaluate the newly developed
      Siemens ADVIA Centaur enhanced Estradiol (eE2) assay and compare it with a well
      established estradiol liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method. DESIGN AND METHODS: The Siemens eE2 assay was evaluated using the
      Clinical and Laboratory Standards Institute evaluation protocols. Split patient
      samples were compared with the eE2 assay, the current ADVIA Centaur E2-6 Ill
      assay; and LC-MS/MS method by API5000 mass spectrometer. RESULTS: Within-run and
      total imprecision of the eE2 assay demonstrated coefficient of variations of
      5.7%, 3.2%, 1.5%, and 10.4%, 7.3%, and 6.8%, at levels of 380, 752, and 2051
      pmol/L, respectively. The method comparisons showed: eE2=0.903(E2-6 III) -16.2,
      R(2)=0.938, average bias=-12.3%; and eE2=0.946(LC-MS/MS)+19.5, R(2)=0.925,
      average bias: 0%. CONCLUSION: The Siemens eE2 assay correlates well with LC
      MS/MS. This method is reliable, and appropriate for routine clinical laboratory
      use.

PMID- 22391027
TI  - Urinary iodine and sodium status of urban Korean subjects: a pilot study.
AB  - OBJECTIVES: We estimated iodine status of Korean population by determining the
      concentration of spot urinary iodine (UI) with a reliable method based on the
      Sandell-Kolthoff reaction. MATERIALS AND METHODS: A total of 540 urine samples
      from apparently healthy subjects were collected, and UI, urinary sodium (UNa),
      and urinary creatinine (UCr) were determined from those samples and analyzed with
      age. RESULTS: There were significant decreases in either UI (P<0.0001), UI/UCr
      ratio (P=0.0001), UNa (P<0.0001), or UNa/Cr ratio (P=0.0001) in younger subjects
      than older ones. The median value of UI was 267.6 MUg/L, but the median UI of the
      younger group (191.8 MUg/L) was significantly decreased compared to that of the
      older group (383.9 MUg/L). CONCLUSIONS: This study showed that the median of UI
      in Korean urban population was in a more than adequate iodine nutritional state,
      but UI was significantly different between the younger age group and the older
      age group.

PMID- 22391028
TI  - Spectrophotometric assay for serum glutathione transferase: a re-examination.
AB  - OBJECTIVES: The aim of the present paper is a careful re-examination of an
      automated spectrophotometric procedure for glutathione transferase (GST) activity
      in human serum described previously and used in many laboratories. DESIGN AND
      METHODS: GST activity in human serum has been assayed spectrophotometrically
      under various experimental conditions. Recombinant human GSTs and specific
      inhibitors were also used to check the possible occurrence of artifacts. RESULTS:
      Basal level of the enzyme calculated using this method turns out to be much
      higher than that found using RIA and ELISA procedures. Relevant pH-dependent
      artifacts deeply affect this spectrophotometric assay. Notably, spectral changes
      previously interpreted as a measure of basal activity, are mainly due to an
      increase of the spontaneous reaction between the two substrates. CONCLUSION: GST
      activity in normal serum cannot be correctly determined with the
      spectrophotometric assay described previously because of the very low enzyme
      concentration and the pH-dependent artifacts.

PMID- 22391029
TI  - Can successful cancer therapies build on what we learn from complex disorders?

PMID- 22391030
TI  - Glutamate-based depression GBD.
AB  - We describe a new term: glutamate-based depression (GBD). GBD is defined as a
      chronic depressive illness associated with environmental stress and diseases
      associated with altered glutamate neurotransmission. We hypothesize that
      glutamate-induced over-activation of extrasynaptic NMDA receptors in the
      subgenual cingulate area called Brodmann's 25 plays an important role in the
      etiology of depression and may be responsible for the high incidence of co-morbid
      depression associated in diseases with glutamate etiology. While depression is a
      syndrome with multiple possible etiologies, we propose that a disruption in
      glutamatergic neurotransmission may underline a substantial proportion of
      clinically observed depression. The high rates of depressive symptoms associated
      with various disorders in which altered glutamatergic functions have been
      identified, may suggest a common pathophysiological mechanism is underlying the
      diverse clinical presentations.

PMID- 22391031
TI  - Tumour metastasis as an adaptation of tumour cells to fulfil their phosphorus
      requirements.
AB  - Inorganic phosphate (Pi) is a vital component of nucleotides, membrane
      phospholipids, and phosphorylated intermediates in cellular signalling. The
      Growth Rate Hypothesis (GRH) states that fast growing organisms should be richer
      in phosphorus (relatively low C:P and N:P cell content) than slow developing
      organisms as a result of high ribosome biogenesis. Cells that proliferate
      rapidly, such as cancer cells, require a high amount of ribosomes and other P
      rich RNA components that are necessary to manufacture proteins. The GRH
      hypothesis may be applied to cancer predicting that tumour cells are richer in
      phosphorus than the surrounding tissue, and that they resort to metastasis in
      order to meet their nutrient demands. Considering that the cells most P-deprived
      should be located in the inner parts of the tumour we propose that changes in the
      membrane of these cells favour the detachment of the more peripheral cells.

PMID- 22391033
TI  - Design, synthesis, and biological evaluation of 4-arylmethyl-1-phenylpyrazole and
      4-aryloxy-1-phenylpyrazole derivatives as novel androgen receptor antagonists.
AB  - A series of 4-arylmethyl-1-phenylpyrazole and 4-aryloxy-1-phenylpyrazole
      compounds B were designed, synthesized, and evaluated for their potential as new
      generation androgen receptor (AR) antagonists therapeutically effective against
      castration-resistant prostate cancer (CRPC). Introduction of a bulky amide
      substituent (R(2)) to the terminal aryl ring of the 4-arylmethyl group favored
      the reduction of agonistic activity and improved the pharmacokinetic (PK)
      properties. Similarly, introduction of a bulky substituent in the 4-aryloxy
      derivatives also resulted in improved PK properties. Compounds 28 h and 44b
      exhibited potent antitumor effects against a CRPC model of LNCaP-hr cell line in
      a mouse xenograft model. On the contrary, bicalutamide showed only partial
      suppression of tumor growth. These results suggest that the novel pyrazole
      derivatives are new-generation AR antagonists, different from the 'first
      generation' antagonists such as bicalutamide in a CRPC treatment model.

PMID- 22391032
TI  - Generation and exploration of new classes of antitubercular agents: The
      optimization of oxazolines, oxazoles, thiazolines, thiazoles to imidazo[1,2
      a]pyridines and isomeric 5,6-fused scaffolds.
AB  - Tuberculosis (TB) is a devastating disease resulting in a death every 20s. Thus,
      new drugs are urgently needed. Herein we report ten classes of compounds
      oxazoline, oxazole, thiazoline, thiazole, pyrazole, pyridine, isoxazole,
      imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine and imidazo[1,2-c]pyrimidine
      which have good (micromolar) to excellent (sub-micromolar) antitubercular
      potency. The 5,6-fused heteroaromatic compounds were the most potent with MIC's
      as low as <0.195 MUM (9 and 11). Overall, the imidazo[1,2-a]pyridine class was
      determined to be most promising, with potency similar to isoniazid and PA-824
      against replicating Mtb H(37)Rv, clinically relevant drug sensitive, multi- and
      extensively resistant Mtb strains as well as having good in vitro metabolic
      stability.

PMID- 22391034
TI  - Orna Cohen-Fix: playing with nuclear morphology. Interview by Caitlin Sedwick.

PMID- 22391035
TI  - The cell biology of regeneration.
AB  - Regeneration of complex structures after injury requires dramatic changes in
      cellular behavior. Regenerating tissues initiate a program that includes diverse
      processes such as wound healing, cell death, dedifferentiation, and stem (or
      progenitor) cell proliferation; furthermore, newly regenerated tissues must
      integrate polarity and positional identity cues with preexisting body structures.
      Gene knockdown approaches and transgenesis-based lineage and functional analyses
      have been instrumental in deciphering various aspects of regenerative processes
      in diverse animal models for studying regeneration.

PMID- 22391036
TI  - JunB contributes to Id2 repression and the epithelial-mesenchymal transition in
      response to transforming growth factor-beta.
AB  - The process of epithelial-mesenchymal transition (EMT) in response to
      transforming growth factor-beta (TGF-beta) contributes to tissue fibrosis, wound
      healing, and cancer via a mechanism that is not fully understood. This study
      identifies a critical role of JunB in the EMT and profibrotic responses to TGF
      beta. Depletion of JunB by small interfering ribonucleic acid abrogates TGF-beta
      induced disruption of cell-cell junctions, formation of actin fibers, focal
      adhesions, and expression of fibrotic proteins. JunB contributes to Smad-mediated
      repression of inhibitor of differentiation 2 through interaction with
      transcription repressor activating transcription factor 3. Importantly, JunB
      mediates the TGF-beta induction of profibrotic response factors, fibronectin,
      fibulin-2, tropomyosin (Tpm1), and integrin-beta3, which play critical roles in
      matrix deposition, cell-matrix adhesion, and actin stress fibers. In summary,
      JunB provides important input in setting the transcriptional program of the EMT
      and profibrotic responses to TGF-beta. Thus, JunB represents an important target
      in diseases associated with EMT, including cancer and fibrosis.

PMID- 22391038
TI  - Vinculin associates with endothelial VE-cadherin junctions to control force
      dependent remodeling.
AB  - To remodel endothelial cell-cell adhesion, inflammatory cytokine- and angiogenic
      growth factor-induced signals impinge on the vascular endothelial cadherin (VE
      cadherin) complex, the central component of endothelial adherens junctions. This
      study demonstrates that junction remodeling takes place at a molecularly and
      phenotypically distinct subset of VE-cadherin adhesions, defined here as focal
      adherens junctions (FAJs). FAJs are attached to radial F-actin bundles and marked
      by the mechanosensory protein Vinculin. We show that endothelial hormones
      vascular endothelial growth factor, tumor necrosis factor alpha, and most
      prominently thrombin induced the transformation of stable junctions into FAJs.
      The actin cytoskeleton generated pulling forces specifically on FAJs, and
      inhibition of Rho-Rock-actomyosin contractility prevented the formation of FAJs
      and junction remodeling. FAJs formed normally in cells expressing a Vinculin
      binding-deficient mutant of alpha-catenin, showing that Vinculin recruitment is
      not required for adherens junction formation. Comparing Vinculin-devoid FAJs to
      wild-type FAJs revealed that Vinculin protects VE-cadherin junctions from opening
      during their force-dependent remodeling. These findings implicate Vinculin
      dependent cadherin mechanosensing in endothelial processes such as leukocyte
      extravasation and angiogenesis.

PMID- 22391039
TI  - The CXCR2 antagonist, SCH-527123, shows antitumor activity and sensitizes cells
      to oxaliplatin in preclinical colon cancer models.
AB  - Colorectal cancer is the second most common cause of cancer-related death in the
      United States. Recent studies showed that interleukin-8 (IL-8) and its receptors
      (CXCR1 and CXCR2) are significantly upregulated in both the tumor and its
      microenvironment, and act as key regulators of proliferation, angiogenesis, and
      metastasis. Our previous study showed that IL-8 overexpression in colorectal
      cancer cells triggers the upregulation of the CXCR2-mediated proliferative
      pathway. The aim of this study was to investigate whether the CXCR2 antagonist,
      SCH-527123, inhibits colorectal cancer proliferation and if it can sensitize
      colorectal cancer cells to oxaliplatin both in vitro and in vivo. SCH-527123
      showed concentration-dependent antiproliferative effects in HCT116, Caco2, and
      their respective IL-8-overexpressing variants colorectal cancer cell lines.
      Moreover, SCH-527123 was able to suppress CXCR2-mediated signal transduction as
      shown through decreased phosphorylation of the NF-kappaB/mitogen-activated
      protein kinase (MAPK)/AKT pathway. These findings corresponded with decreased
      cell migration and invasion, while increased apoptosis in colorectal cancer cell
      lines. In vivo results verified that SCH-527123 treatment decreased tumor growth
      and microvessel density when compared with vehicle-treated tumors. Importantly,
      these preclinical studies showed that the combination of SCH-527123 and
      oxaliplatin resulted in a greater decrease in cell proliferation, tumor growth,
      apoptosis, and angiogenesis that was superior to single-agent treatment. Taken
      together, these findings suggest that targeting CXCR2 may block tumor
      proliferation, migration, invasion, and angiogenesis. In addition, CXCR2 blockade
      may further sensitize colorectal cancer to oxaliplatin treatment.

PMID- 22391041
TI  - Medical journal editor and scientific publication issue.

PMID- 22391040
TI  - Ictal high-gamma oscillation (60-99 Hz) in intracranial electroencephalography
      and postoperative seizure outcome in neocortical epilepsy.
AB  - OBJECTIVE: High-gamma oscillations (HGOs) (60-99 Hz) have been suggested to
      correlate with seizure onset zones and seizure outcomes. We investigated the
      correlation between the extent of removal of ictal HGO generating areas and
      postoperative seizure outcome in neocortical epilepsy (NE). METHODS: Twenty three
      patients with medically intractable NE underwent chronic intracranial
      electroencephalography (iEEG) using subdural electrodes. Ictal HGOs and
      superimposed undersampled ripples within +/-3 s of video-iEEG ictal onset were
      extracted by wavelet clustering and thresholding. Cluster epileptogenicity
      indices (CEIs) were calculated. The temporal analysis window was locked to the
      timing of the maximum CEI wavecluster. Root mean square amplitudes, cross
      correlation synchronies and the local focus indices within the temporal window
      were calculated. RESULTS: Percentages of resected maximum CEI waveclusters and
      HGO zones with high standardised amplitudes (>3), high cross-correlation
      synchronies (>0.9) and high local focus indices (>2) were significantly higher in
      the seizure-free group compared to the not seizure-free group (p=0.036, p=0.018,
      and p=0.026, respectively). CONCLUSIONS: The automatic quantitative ictal HGO
      analysis may be effective in delineating the epileptogenic zone. SIGNIFICANCE:
      HGO analysis may be helpful for improving post-resection seizure outcome in NE in
      the future.

PMID- 22391037
TI  - Drosophila CK1-gamma, gilgamesh, controls PCP-mediated morphogenesis through
      regulation of vesicle trafficking.
AB  - Cellular morphogenesis, including polarized outgrowth, promotes tissue shape and
      function. Polarized vesicle trafficking has emerged as a fundamental mechanism by
      which protein and membrane can be targeted to discrete subcellular domains to
      promote localized protrusions. Frizzled (Fz)/planar cell polarity (PCP) signaling
      orchestrates cytoskeletal polarization and drives morphogenetic changes in such
      contexts as the vertebrate body axis and external Drosophila melanogaster
      tissues. Although regulation of Fz/PCP signaling via vesicle trafficking has been
      identified, the interplay between the vesicle trafficking machinery and
      downstream terminal PCP-directed processes is less established. In this paper, we
      show that Drosophila CK1-gamma/gilgamesh (gish) regulates the PCP-associated
      process of trichome formation through effects on Rab11-mediated vesicle
      recycling. Although the core Fz/PCP proteins dictate prehair formation broadly,
      CK1-gamma/gish restricts nucleation to a single site. Moreover, CK1-gamma/gish
      works in parallel with the Fz/PCP effector multiple wing hairs, which restricts
      prehair formation along the perpendicular axis to Gish. Our findings suggest that
      polarized Rab11-mediated vesicle trafficking regulated by CK1-gamma is required
      for PCP-directed processes.

PMID- 22391042
TI  - CR3-dependent negative regulation of human eosinophils by Mycobacterium bovis BCG
      lipoarabinomannan.
AB  - Eosinophils have recently been shown to participate in innate immune responses
      against mycobacteria. We have investigated whether Mycobacterium bovis BCG
      regulate the human eosinophil immune response. A negative correlation between
      mycobacteria internalization and eosinophil activation was observed. In addition,
      mannose-capped lipoarabinomannan from M. bovis BCG (ManLAM) failed to induce a
      significant release of eosinophil peroxidase and TNF-alpha. Noteworthy, ManLAM
      exhibited a potent inhibitory effect on eosinophil peroxidase release by TLR2
      activated eosinophils involving the complement receptor-3 molecule and the
      phosphatidylinositol-3 kinase pathway. ManLAM, generally present in pathogenic
      mycobacteria, plays an important role in modulating eosinophil-dependent immune
      response.

PMID- 22391044
TI  - Elevated plasma glucose-dependent insulinotropic polypeptide associates with
      hyperinsulinemia in metabolic syndrome.
AB  - BACKGROUND AND AIMS: Metabolic syndrome (MS) is a high-risk condition for type 2
      diabetes, a disease characterized by insulin resistance and insulin secretion
      abnormalities. Insulin resistance has been widely characterized in MS subjects
      while insulin secretion has been poorly investigated. The present study was hence
      undertaken to further investigate the alpha and beta cell function and entero
      insular axis in this pre-diabetic condition. MATERIALS AND METHODS: Using 120'
      oral glucose tolerance test (OGTT, 75  g) and 60' intravenous glucose tolerance
      test (IVGTT, 0.3  g/kg), we studied alpha and beta cell function, insulin
      resistance, and incretin levels in 96 subjects with normal fasting glucose and
      normal glucose tolerance to OGTT, with (MS+, n=29) and without MS (MS-, n=67).
      RESULTS: MS+ individuals showed in comparison with MS-: higher insulinogenic
      index (IG30) and higher area under the curve (AUC) (0-120) for glucose and
      insulin during the OGTT, P<0.05; higher AUC (0-10) for glucose (P<0.05) but
      similar first phase insulin secretion (P=NS) as measured by DeltaAIRG and AUC (0
      10) for insulin during the IVGTT; increased AUC (0-60) for insulin during the
      IVGTT (P=0.04); higher GIP levels at 30' (P=0.03), 60' (P=0.01), 90' (P=0.003),
      and 120' (P=0.004); higher AUC (0-120) for GIP (P=0.007); similar AUC (0-120) for
      GLP-1 during the OGTT; and delayed glucagon suppression after the OGTT.
      CONCLUSION: NGT subjects with MS showed increased GIP secretion that could be
      responsible for the delayed glucagon suppression during the OGTT, thereby
      suggesting a role for incretins in regulating glucose homeostasis in this
      condition.

PMID- 22391045
TI  - Iterative 4D cardiac micro-CT image reconstruction using an adaptive spatio
      temporal sparsity prior.
AB  - Temporal-correlated image reconstruction, also known as 4D CT image
      reconstruction, is a big challenge in computed tomography. The reasons for
      incorporating the temporal domain into the reconstruction are motions of the
      scanned object, which would otherwise lead to motion artifacts. The standard
      method for 4D CT image reconstruction is extracting single motion phases and
      reconstructing them separately. These reconstructions can suffer from
      undersampling artifacts due to the low number of used projections in each phase.
      There are different iterative methods which try to incorporate some a priori
      knowledge to compensate for these artifacts. In this paper we want to follow this
      strategy. The cost function we use is a higher dimensional cost function which
      accounts for the sparseness of the measured signal in the spatial and temporal
      directions. This leads to the definition of a higher dimensional total variation.
      The method is validated using in vivo cardiac micro-CT mouse data. Additionally,
      we compare the results to phase-correlated reconstructions using the FDK
      algorithm and a total variation constrained reconstruction, where the total
      variation term is only defined in the spatial domain. The reconstructed datasets
      show strong improvements in terms of artifact reduction and low-contrast
      resolution compared to other methods. Thereby the temporal resolution of the
      reconstructed signal is not affected.

PMID- 22391046
TI  - Remediation of toxic metal contaminated soil by washing with biodegradable
      aminopolycarboxylate chelants.
AB  - Ex situ soil washing with synthetic extractants such as, aminopolycarboxylate
      chelants (APCs) is a viable treatment alternative for metal-contaminated site
      remediation. EDTA and its homologs are widely used among the APCs in the ex situ
      soil washing processes. These APCs are merely biodegradable and highly persistent
      in the aquatic environments leading to the post-use toxic effects. Therefore, an
      increasing interest is focused on the development and use of the eco-friendly
      APCs having better biodegradability and less environmental toxicity. The paper
      deals with the results from the lab-scale washing treatments of a real sample of
      metal-contaminated soil for the removal of the ecotoxic metal ions (Cd, Cu, Ni,
      Pb, and Zn) using five biodegradable APCs, namely [S,S]-ethylenediaminedisuccinic
      acid, imminodisuccinic acid, methylglycinediacetic acid, DL-2-(2-carboxymethyl)
      nitrilotriacetic acid (GLDA), and 3-hydroxy-2,2'-iminodisuccinic acid. The
      performance of those biodegradable APCs was evaluated for their interaction with
      the soil mineral constituents in terms of the solution pH and metal-chelant
      stability constants, and compared with that of EDTA. Speciation calculations were
      performed to identify the optimal conditions for the washing process in terms of
      the metal-chelant interactions as well as to understand the selectivity in the
      separation ability of the biodegradable chelants towards the metal ions. A linear
      relationship between the metal extraction capacity of the individual chelants
      towards each of the metal ions from the soil matrix and metal-chelant conditional
      stability constants for a solution pH greater than 6 was observed. Additional
      considerations were derived from the behavior of the major potentially
      interfering cations (Al, Ca, Fe, Mg, and Mn), and it was hypothesized that use of
      an excess of chelant may minimize the possible competition effects during the
      single-step washing treatments. Sequential extraction procedure was used to
      determine the metal distribution in the soil before and after the extractive
      decontamination using biodegradable APCs, and the capability of the APCs in
      removing the metal ions even from the theoretically immobilized fraction of the
      contaminated soil was observed. GLDA appeared to possess the greatest potential
      to decontaminate the soil through ex situ washing treatment compared to the other
      biodegradable chelants used in the study.

PMID- 22391043
TI  - Neonatal +-methamphetamine exposure in rats alters adult locomotor responses to
      dopamine D1 and D2 agonists and to a glutamate NMDA receptor antagonist, but not
      to serotonin agonists.
AB  - Neonatal exposure to (+)-methamphetamine (Meth) results in long-term behavioural
      abnormalities but its developmental mechanisms are unknown. In a series of
      experiments, rats were treated from post-natal days (PD) 11-20 (stage that
      approximates human development from the second to third trimester) with Meth or
      saline and assessed using locomotor activity as the readout following
      pharmacological challenge doses with dopamine, serotonin and glutamate agonists
      or antagonists during adulthood. Exposure to Meth early in life resulted in an
      exaggerated adult locomotor hyperactivity response to the dopamine D1 agonist SKF
      82958 at multiple doses, a high dose only under-response activating effect of the
      D2 agonist quinpirole, and an exaggerated under-response to the activating effect
      of the N-methyl-d-aspartic acid (NMDA) receptor antagonist, MK-801. No change in
      locomotor response was seen following challenge with the 5-HT releaser p
      chloroamphetamine or the 5-HT2/3 receptor agonist, quipazine. These are the first
      data to show that PD 11-20 Meth exposure induces long-lasting alterations to
      dopamine D1, D2 and glutamate NMDA receptor function and may suggest how
      developmental Meth exposure leads to many of its long-term adverse effects.

PMID- 22391047
TI  - Evaluation of the possible adverse effects of legacy persistent organic
      pollutants (POPs) on the brown booby (Sula leucogaster) along the Brazilian
      coast.
AB  - This study aimed to investigate the impact of contamination by persistent organic
      pollutants (POPs) on Brazilian wildlife. The concentrations of certain POPs,
      including dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls
      (PCBs), in the eggs of the brown booby (Sula leucogaster) were measured. The eggs
      were collected from breeding colonies located on three archipelagos (Saint Peter
      and Saint Paul, Abrolhos and Cagarras Islands) in the Atlantic Ocean, which are
      located at different distances from the Brazilian coast (range 4-1010 km). In
      addition, possible alterations in eggshell characteristics were evaluated. The
      average values of POPs found in eggs from the archipelago of Saint Peter and
      Saint Paul (0.05MUgg(-1) of SigmaPCBs and 0.01 MUg g(-1) of SigmaDDT) and the
      archipelago of Abrolhos (0.19 MUg g(-1) of SigmaPCBs and 0.03 MUg g(-1) of
      SigmaDDT) were low compared to the reference values reported in the literature.
      In contrast, the concentrations measured in eggs from Cagarras (8.4 MUg g(-1) of
      SigmaPCBs and 1.8 MUg g(-1) of SigmaDDT) were the highest, and this total PCB
      level is close to the threshold values considered to be harmful to birds. Our
      findings indicate that the brown booby colony closest to the Rio de Janeiro coast
      has recently been exposed to DDT. Despite the high pollution levels found on the
      Cagarras Islands, no alterations in the eggshell weight or the thickness of the
      analyzed eggs were detected. Hence, more detailed studies are recommended to
      determine the actual effects of the selected POPs on the Cagarras breeding
      colony.

PMID- 22391048
TI  - Behavior of perfluorinated compounds in soils during leaching experiments.
AB  - Perfluorinated compounds (PFCs) can be detected worldwide in both, soil and
      water. In order to study the leaching behavior of this heterogeneous group of
      compounds in soil, flow-through column experiments have been conducted. Ten
      perfluoro carboxylates and four perfluoro sulfonates ranging from C4 to C14 in
      chain length, and contaminated sewage sludge, have been used to spike a standard
      soil. The aqueous column effluent was analyzed using liquid chromatography tandem
      mass spectrometry (LC-MS/MS) with direct injection. The observed percolation
      velocity seems to be strongly correlated with the length of the perfluorinated
      chain. Other factors that additionally contribute to the leaching behavior are
      the functional group of the PFC, the organic carbon content of the soil and the
      presence of other adsorbates. A mass balance calculation showed that
      perfluorobutanoic acid can adsorb strongly to the soil, when no PFC with longer
      carbon chain are present. Only about 60% of the added perfluorobutanoic acid
      could be detected in the percolate water. The missing amount started to elute
      again when longer chain PFC or stearate were added to the soil. Thus it would
      appear that larger and more lipophilic molecules can displace shorter PFC from
      their binding sites in the soil. The results of a monitoring study using 32
      surface water samples and 150 groundwater samples confirm that the PFC with the
      highest concentrations in groundwater are the short chain PFC with less than 7
      (fluorinated) carbon atoms. The dominating PFC in surface waters are
      perfluorooctanoic acid and perfluorooctane sulfonic acid.

PMID- 22391049
TI  - Atmospheric concentrations of PCDD/Fs, dl-PCBs and some pesticides in northern
      Algeria using passive air sampling.
AB  - Two monitoring campaigns were conducted in northern Algeria to assess the
      contamination level of pesticides and persistent organic pollutants (POPs) in
      ambient air. Six pesticides (alpha- and gamma-hexachlorocyclohexane,
      fenitrothion, malathion, chlorpyrifos and lambda-cyhalothrin) were monitored at
      two different sampling locations during the first campaign. The passive sampling
      was performed at a semi urban/industrial site but also in a rural area between
      July to September 2008. The pesticides levels, analyzed by GC/MS/MS, ranged from
      16 pg m(-3) to 11 ng m(-3). The second campaign was carried out from May to
      November 2009. The polychlorodibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and
      dioxin-like polychlorinated biphenyls (dl-PCBs) concentrations were evaluated at
      an urban/industrial and at an industrial site. The PCDD/Fs and dl-PCBs, analyzed
      by HRGC/HRMS, ranged from 249 to 923 fg TEQ m(-3). In addition to passive
      sampling, active sampling using an isokinetic sampler was also performed at an
      industrial waste incinerator. The PCDD/Fs and dl-PCBs found was 268 pg TEQ m(-3).
      This paper presents the first measurements of PCDD/Fs, dl-PCBs and pesticides in
      rural, urban and industrial areas of northern Algeria.

PMID- 22391051
TI  - Behavioural processes in social context: female abductions, male herding and
      female grooming in hamadryas baboons.
AB  - The formation of bonds between strangers is an event that occurs routinely in
      many social animals, including humans, and, as social bonds in general, they
      affect the individuals' welfare and biological fitness. The present study was
      motivated by an interest in the behavioural processes that drive bond formation
      in a social context of hostility, in which the incumbent partners vary greatly in
      physical power and reproductive interests, a situation in which individuals of
      many group-living species find themselves often throughout their lives. We
      focused on the quantitative analysis of female abductions via male aggressive
      herding in a nonhuman primate, the hamadryas baboon, in which intersexual bonds
      are known to be strong. We tested three hypotheses informed by sexual
      conflict/sexual coercion theory (male herding-as-conditioning and female grooming
      as-appeasement) and by socioecological theory (unit size and female competition).
      The results supported the predictions: males resorted to coercive tactics
      (aggressive herding) with abducted females, and abducted females elevated the
      amount of grooming directed at their new unit males; in fact, they escaped from
      the otherwise negative effect of unit size on female-to-male grooming. These
      findings reveal that conflicts of interest are natural ingredients underpinning
      social bonds and that resorting to coercive aggression may be an option
      especially when partners differ greatly in their physical power.

PMID- 22391050
TI  - Organochlorine compounds in mussels cultured in the Ria of Vigo: accumulation and
      origin.
AB  - This paper analyzes the influence of mussel physiological conditions on
      bioaccumulation of organochlorine pollutants. A direct relationship between
      reproductive stage, lipid content and accumulation of PCBs, DDTs and HCHs was
      observed. The organochlorine compounds accumulated by mussels cultured in the Ria
      of Vigo show levels below the limits set by the European legislation for human
      consumption, ranging between 12.50-58, 2.21-10.80 and 0.50-2.69 MUg kg(-1) dry
      weight for PCBs, DDTs and HCHs, respectively. Other organochlorine pesticides
      normally present in estuarine areas, such as hexachlorobenzene (HCB), aldrin,
      chlordane and nonachlor were not detected. The proportion of PCBs, between 2 and
      7 times higher than OCPs, indicates a pollution of predominantly industrial
      origin in the sampling area. Several molecular indices were used to identify the
      source of accumulated OCPs by Mytilus, showing recent inputs of technical DDT,
      mainly in summer-autumn, and continued discharges of lindane. On the other hand,
      other pesticides containing DDT impurities, such as dicofol, can contribute to
      DDT pollution in the Ria of Vigo. Multivariate analysis suggests the usefulness
      of including physiological parameters such as the gonad condition index and lipid
      content of sentinel organisms in environmental biomonitoring of lipophilic
      pollutants, as well as in the determination of their origin.

PMID- 22391053
TI  - Adjuvant radiation therapy for early stage seminoma: proton versus photon
      planning comparison and modeling of second cancer risk.
AB  - PURPOSE: Given concerns of excess malignancies following adjuvant radiation for
      seminoma, we evaluated photon and proton beam therapy (PBT) treatment plans to
      assess dose distributions to organs at risk and model rates of second cancers.
      MATERIALS AND METHODS: Ten stage I seminoma patients who were treated with
      conventional para-aortic AP-PA photon radiation to 25.5 Gy at Massachusetts
      General Hospital had PBT plans generated (AP-PA, PA alone). Dose differences to
      critical organs were examined. Risks of second primary malignancies were
      calculated. RESULTS: PBT plans were superior to photons in limiting dose to
      organs at risk. PBT decreased dose by 46% (8.2 Gy) and 64% (10.2 Gy) to the
      stomach and large bowel, respectively (p<0.01). Notably, PBT was found to avert
      300 excess second cancers among 10,000 men treated at a median age of 39 and
      surviving to 75 (p<0.01). CONCLUSIONS: In this study, the use of protons provided
      a favorable dose distribution with an ability to limit unnecessary exposure to
      critical normal structures in the treatment of early-stage seminoma. It is
      expected that this will translate into decreased acute toxicity and reduced risk
      of second cancers, for which prospective studies are warranted.

PMID- 22391052
TI  - Combinatorial use of translational co-factors for cell type-specific regulation
      during neuronal morphogenesis in Drosophila.
AB  - The translational regulators Nanos (Nos) and Pumilio (Pum) work together to
      regulate the morphogenesis of dendritic arborization (da) neurons of the
      Drosophila larval peripheral nervous system. In contrast, Nos and Pum function in
      opposition to one another in the neuromuscular junction to regulate the
      morphogenesis and the electrophysiological properties of synaptic boutons.
      Neither the cellular functions of Nos and Pum nor their regulatory targets in
      neuronal morphogenesis are known. Here we show that Nos and Pum are required to
      maintain the dendritic complexity of da neurons during larval growth by promoting
      the outgrowth of new dendritic branches and the stabilization of existing
      dendritic branches, in part by regulating the expression of cut and head
      involution defective. Through an RNA interference screen we uncover a role for
      the translational co-factor Brain Tumor (Brat) in dendrite morphogenesis of da
      neurons and demonstrate that Nos, Pum, and Brat interact genetically to regulate
      dendrite morphogenesis. In the neuromuscular junction, Brat function is most
      likely specific for Pum in the presynaptic regulation of bouton morphogenesis.
      Our results reveal how the combinatorial use of co-regulators like Nos, Pum and
      Brat can diversify their roles in post-transcriptional regulation of gene
      expression for neuronal morphogenesis.

PMID- 22391054
TI  - Radiation-induced cardiac damage in early left breast cancer patients: risk
      factors, biological mechanisms, radiobiology, and dosimetric constraints.
AB  - Today there is general awareness of the potential damage to the heart in left
      sided (more than in right-sided) breast cancer radiotherapy (RT). Historical
      changes in tumor and heart doses are presented here along with the impact of
      different RT techniques and volumes. Individual and pharmacological risk factors
      are also examined with respect to radiation damage. The biological mechanisms of
      harm are only partially understood, such as the radiobiology of heart damage due
      to the presence of various radiosensitive structures and their topographic
      heterogeneity. Furthermore, individual variability may expose patients to higher
      or lower risks of late cardiac damage or death. Damage mechanisms and
      radiobiological characteristics in heart irradiation are presented in relation to
      dosimetric and biological parameters.

PMID- 22391055
TI  - A comparison between slaughter traits and meat quality of various sheep breeds:
      wool, dual-purpose and mutton.
AB  - The slaughter and meat quality traits of 20-month-old wool (Merino), dual-purpose
      (Dohne Merino and South African Mutton Merino [SAMM]) and mutton (Dormer) type
      sheep were compared. Average live weights of SAMM and Dormer sheep were 23%
      heavier than those of Dohne Merinos which were 28% heavier than Merinos. Fat
      depths at the thirteenth rib and lumbar regions of Merino and Dohne Merino sheep
      were lower than those of SAMM and Dormer sheep. The cooking loss, drip loss and
      shearing value from the M. longissimus dorsi did not differ between breeds. The
      initial juiciness and sustained juiciness of meat from Merinos were rated
      significantly lower by sensory analysis. Meat from Dohne Merino was rated
      significantly more tender for the attribute first bite. It was demonstrated that
      Dormer and SAMM sheep had heavier but fatter carcasses than Merinos and Dohne
      Merinos, with differences in meat quality between breeds.

PMID- 22391056
TI  - Lysine, disodium guanylate and disodium inosinate as flavor enhancers in low
      sodium fermented sausages.
AB  - Fermented sausages were produced with 50% replacement of NaCl with KCl and with
      addition of lysine, disodium guanylate, and disodium inosinate. The sausage
      production was monitored with physical, chemical and microbiological analyses.
      The final products were submitted to a consumer study. The replacement of NaCl
      with KCl did not cause changes in the technological process. However, defects in
      the sensory quality were detected. Lysine at a concentration of 1% with disodium
      inosinate (300 mg/kg) and disodium guanylate (300 mg/kg) reduced the sensory
      defects caused by the replacement of 50% NaCl with KCl allowing the preparation
      of sensory acceptable fermented sausages with a 50% decrease in sodium.

PMID- 22391057
TI  - Impact of oxygen plasma treatment on the device performance of zinc oxide
      nanoparticle-based thin-film transistors.
AB  - Thin-films of zinc oxide nanoparticles were investigated by photoluminescence
      spectroscopy and a broad defect-related yellow-green emission was observed.
      Oxygen plasma treatment was applied in order to reduce the number of defects, and
      the emission intensity was quenched to 4% of the initial value. Thin-film
      transistors that incorporate the nanoparticles as active semiconducting layers
      show an improved device performance after oxygen plasma treatment. The maximum
      drain current and the charge carrier mobility increased more than 1 order of
      magnitude up to a nominal value of 23 cm(2) V(-1) s(-1) and the threshold voltage
      was lowered.

PMID- 22391058
TI  - A computational model of use-dependent motor recovery following a stroke:
      optimizing corticospinal activations via reinforcement learning can explain
      residual capacity and other strength recovery dynamics.
AB  - This paper describes a computational model of use-dependent recovery of movement
      strength following a stroke. The model frames the problem of strength recovery as
      that of learning appropriate activations of residual corticospinal neurons to
      their target motoneuronal pools. For example, for an agonist/antagonist muscle
      pair, we assume the motor system must learn to activate preserved agonist
      exciting corticospinal neurons and deactivate preserved antagonist-exciting
      corticospinal neurons. The model incorporates a biologically plausible
      reinforcement learning algorithm for adjusting cell activation patterns
      stochastic search-using generated limb force as the teaching signal to adjust the
      synaptic weights that determine cell activations. The model makes predictions
      consistent with clinical and brain imaging data, such as that patients can
      achieve an increase in strength after appearing to reach a recovery plateau
      (i.e., "residual capacity"), that the differential effect of a dose of movement
      practice will be greater earlier in recovery, and that force-related brain
      activation will increase in secondary motor areas following a stroke. An
      interesting prediction that could be explored clinically is that temporarily
      inhibiting subpopulations of more powerfully connected corticospinal neurons
      during late movement training will allow the motor system to optimize
      corticospinal neurons with a weaker influence, whose optimization was blocked by
      the rapid optimization of more strongly connected neurons early in training.

PMID- 22391059
TI  - Serum osteoprotegerin: bone or cardiovascular marker in Type 2 diabetes males?
AB  - BACKGROUND: The role of osteoprotegerin (OPG) as a marker of cardiovascular
      disease (CVD) in Type 2 diabetes (T2DM) is not well established. Moreover, the
      relationship between OPG, osteoporosis, and vertebral fractures in T2DM remains
      to be elucidated. AIM: To determine the role of serum OPG in the prediction of
      CVD and bone disease in T2DM males. SUBJECTS AND METHODS: Cross-sectional study
      with 68 males, 43 with T2DM and 25 subjects without diabetes. We measured: serum
      OPG by inmunoassay, the presence of CVD (coronary heart disease, cerebrovascular
      and peripheral artery disease), surrogate markers of CVD [intima- media thickness
      (IMT) and aortic calcification] and bone disease (bone mineral density and
      prevalent vertebral fractures). RESULTS: OPG serum levels (in pmol/l) were
      significantly higher in T2DM males with abnormal IMT (5.12 +/- 1.59 vs 3.76 +/-
      1.98), carotid plaque (5.46 +/- 1.67 vs 4.20 +/- 1.81), aortic calcification
      (5.91 +/- 1.39 vs 4.07 +/- 1.76), hypertension (5.11 +/- 1.86 vs 3.81 +/- 1.47),
      and peripheral artery disease (6.24 +/- 1.64 vs 4.21 +/- 1.63, p < 0.05 for all
      comparisons). In the logistic regression analysis (after adjustment for age and
      main cardiovascular risk factors), serum OPG (per 1 pmol/l increase in OPG) was
      associated with increased risk of abnormal IMT [odds ratio (OR) 1.84, confidence
      interval (CI) 1.21-2.79, p = 0.004), carotid plaque (OR 1.71, CI 1.13-2.58, p =
      0.012), aortic calcification (OR 2.21, CI 1.27-3.84, p = 0.05) and peripheral
      artery disease (OR 4.02, CI 1.65-9.8 p = 0.002). However, OPG were not related to
      bone mass or vertebral fractures. CONCLUSIONS: Our results suggest that in T2DM
      males OPG serum concentrations constitute a marker of CVD, but not a marker of
      bone disease.

PMID- 22391060
TI  - Potential health benefits of moderate alcohol consumption: current perspectives
      in research.
AB  - The benefits of moderate amounts of alcohol for a better health and longer life
      expectancy compared with abstinence have been suggested by the findings of
      numerous studies. However, controversies have emerged regarding the influence of
      confounding factors and the systematic errors that might have been inadvertently
      disregarded in the early studies. This review includes a description of the
      findings of those research studies published in the last 5 years on the effects
      of moderate alcohol consumption on all-cause mortality, CVD and inflammation, the
      immune system, insulin sensitivity, non-alcoholic fatty liver disease (NAFLD) and
      cancer. Promising evidences exist from both animal studies and human clinical
      trials regarding intermediate end-points of CHD and insulin sensitivity, such as
      HDL, adiponectin or fibrinogen. However, controversies and inconsistent findings
      exist regarding many of these diseases and related functions and biomarkers.
      Further research and human randomised-controlled trials with adequate
      standardisation of the study conditions are necessary in order to draw a
      comparison between studies, establish the causal effect of moderate alcohol
      intake on disease protection and reach consensus on the circumstances that allow
      the recommendation of moderate alcohol habitual intakes as a strategy for health
      maintenance.

PMID- 22391061
TI  - Retro peptide-hybrids as selective inhibitors of the Dengue virus NS2B-NS3
      protease.
AB  - New chemotherapeutics against Dengue virus and related flaviviruses are of
      growing interest in antiviral drug discovery. The viral serine protease NS2B-NS3
      is a promising target for the development of such agents. Drug-like inhibitors of
      this protease with high affinity to the target are not available at the moment.
      The present work describes the discovery of new retro di- and tripeptide hybrids
      that do not necessarily require an electrophilic "warhead" to achieve affinities
      in the low micromolar range. The most active sequence in this series is the
      tripeptide R-Arg-Lys-Nle-NH(2). By variation of the N-terminal groups (R) it
      could be shown that the previously described arylcyanoacrylamide moiety is a
      preferable group in this position. Retro tripeptide hybrids were found to be more
      active and more selective than retro dipeptide hybrids. A significant selectivity
      towards the Dengue virus protease could be shown in a counterscreen with thrombin
      and the West Nile virus protease. Alternative sequences to R-Arg-Lys-Nle-NH(2)
      did not have higher affinities towards the Dengue virus protease, similar to
      retro-inverse sequences with D-lysine and D-arginine residues. The results of a
      competition assay with the known inhibitor aprotinin indicate that the N-terminal
      arylcyanoacrylamide residue of this compound class binds near the catalytic
      center of the enzyme.

PMID- 22391062
TI  - A comparison of a Monte Carlo-based detection probability matrix with analytical
      probability matrix for small animal PET scanners.
AB  - Positron Emission Tomography (PET) offers the possibility to quantitatively
      measure the radiotracer distribution in tissues. In order to obtain images of
      these tissues, the detection probability matrix (DPM) must be accurately
      determined. Usually, DPM is analytically calculated. However, this approach does
      not take into account the whole probabilistic interactions of the photons. On the
      other hand, Monte Carlo simulations (MC) are more accurate to calculate the DPM
      as they selectively consider diverse photon interactions. In this work, MC DPM
      (MCDPM) and analytically calculated DPM (ACDPM) were compared in terms of image
      quality. The results showed that the images obtained from the MCDPM were
      qualitatively better resolved and provided a significant improvement of the
      signal-to-noise ratio (SNR). The MCDPM yielded to an increase of up to 40% in SNR
      and up to 25% in contrast in comparison with ACDPM. On the other hands, MCDPM
      enhanced the counts distribution by more than 12% with respect to ACDPM.

PMID- 22391063
TI  - Creation of a female and male segmentation dataset based on Chinese Visible Human
      (CVH).
AB  - OBJECTIVE: Segmentation is a necessary step when creating realistic three
      dimensional (3D) models. In order to build 3D models of whole body structures and
      have a wider lateral application, the thin sectional anatomical images of the
      Chinese Visible Human (CVH) dataset should be segmented. The more detailed
      structures are segmented to provide greater potential for wider application of
      the segmented images. MATERIALS AND METHODS: All the images based on the CVH male
      and female dataset were segmented semi-automatically using PHOTOSHOP software.
      This research lasted about 7 years. RESULT: In this study, 869 structures of CVH
      male and 860 structures of CVH female were semi-automatically segmented, and the
      formats for the segmented color-filled image data were PSD and PNG. In these
      segmented structures, nearly all skeletal muscles included muscle belly and
      tendon, and hollow organs included their organ walls and their lumen. Most nerve
      trunks, small arteries, lymph nodes, and lymph ducts were also segmented. Many
      surface-rendering and volume-rendering organ models were created using these
      segmented images. CONCLUSION: The CVH male and female images represent the normal
      Asian population. After segmentation, the images can be reconstructed directly in
      3D and greatly facilitate the biological modeling of physical and physiological
      information, a great help in improving medical and biological science in China.

PMID- 22391064
TI  - Corelationship between matrix metalloproteinase 2 and 9 expression and severity
      of chronic rhinosinusitis with nasal polyposis.
AB  - BACKGROUND: Matrix metalloproteinase (MMP) is involved in the remodeling process
      of inflammatory airway diseases and is correlated with the severity of asthma. We
      hypothesized that MMP was associated with the severity of chronic rhinosinusitis
      with nasal polyps (CRSwNPs).  We also investigated the effect of allergy on the
      expression of MMP in the polyp. METHODS: The expression of MMP-2 and -9 was
      investigated in recurrent nasal polyps of 30 patients and in nonrecurrent nasal
      polyps of 31 patients undergoing endoscopic sinus surgery. These  expressions
      were then compared with those in control nasal mucosal samples obtained from 32
      patients with chronic hypertrophic rhinitis. Demographic data, Lund-Mackay (LM)
      score, polyp grade, and allergy status were obtained for all patients. Tissue
      samples were assessed via immunohistochemistry. RESULTS: MMP-2 and -9 were
      constantly expressed in recurrent NPs, primary NPs, and control nasal mucosa. The
      expression of MMP-9 was significantly enhanced in glands and MMP-2 positivity was
      significantly increased in surface epithelium for patients with NPs when compared
      with  control nasal mucosa. The expression of MMP-9 and -2 was not correlated
      with polyp grade and LM score. Allergic status is an independent factor in the
      expression of MMP-2 and -9. CONCLUSION: These results suggested up-regulation of
      MMP-9, and MMP-2 in gland and surface  epithelium, respectively, were
      characteristic of NPs. Therefore, patients with allergy will exhibit greater MMP
      2 and -9 positivity. However, the MMP-2 and -9 expression intensity was not
      correlated with the severity of CRS with nasal polyposis.

PMID- 22391067
TI  - Effect of simvastatin on transforming growth factor beta-1-induced myofibroblast
      differentiation and collagen production in nasal polyp-derived fibroblasts.
AB  - BACKGROUND: Statins are the most commonly prescribed drugs for the treatment of
      hypercholesterolemia. Statins exert not only lipid-lowering but also other
      cellular effects, including antifibrotic properties. The purpose of this study
      was to determine the effect of simvastatin  on transforming growth factor (TGF)
      beta-1-induced myofibroblast differentiation and collagen production in nasal
      polyp-derived fibroblasts (NPDFs) and to verify the mechanism of the effect of
      simvastatin in TGF-beta-1-induced myofibroblast differentiation in NPDFs.
      METHODS: NPDFs were pretreated with simvastatin with or without mevalonate or Y
      27643 for 2 hours before induction by TGF-beta-1. The expression of alpha-smooth
      muscle actin (SMA) and collagen type IV mRNA was determined by a reverse
      transcription-polymerase chain reaction,  and the expression of alpha-SMA protein
      was determined by immunofluorescent cytochemical staining. Total soluble collagen
      production was analyzed by the SirCol collagen dye-binding assay (Biocolor,
      Belfast, U.K.). Phosphorylation of Smad 2/3 was evaluated by Western blot
      analysis. RESULTS: In TGF-beta-1-induced NPDFs, simvastatin significantly
      inhibited the expressions of alpha-SMA and collagen type IV mRNA and reduced
      alpha-SMA and collagen protein levels. Pretreatment with mevalonate reversed the
      effect of simvastatin. The expression of alpha-SMA  mRNA and protein was
      significantly decreased by pretreatment with Y-27632. The TGF-beta-1-induced
      expression of pSmad 2/3 protein was notably decreased by pretreatment with
      simvastatin. CONCLUSION: We showed that simvastatin inhibits TGF-beta-1-induced
      myofibroblast  differentiation (expression of alpha-SMA) and collagen production
      in NPDFs and Rho/Rock and TGF-beta/Smad signaling is involved as an underlying
      mechanism. The results of our study suggest that simvastatin is a possible
      candidate for the suppression of nasal polyp formation.

PMID- 22391066
TI  - Suppression of connexin 26 is related to protease-activated receptor 2-mediated
      pathway in patients with allergic rhinitis.
AB  - BACKGROUND: Connexin (Cx) 26 plays a key role in maintaining the integrity of
      tight junctions. However, the expression and modulation of Cx26 in allergic
      rhinitis (AR) has not been well understood. METHODS: We detected the expression
      of Cx26 in house-dust  mite (HDM)-sensitized AR patients and investigated the
      Cx26 production and modulation in primary human nasal epithelial cells (HNECs)
      and BEAS-2B cells after treatment with the allergen Der p 1 from Dermatophagoides
      pteronyssinus. RESULTS: We found that the  mRNA and protein levels of Cx26 were
      significantly down-regulated in AR patients compared with the control. Der p 1
      was found to induce protease-activated receptor 2 (PAR2) expression and suppress
      Cx26 production significantly in vitro. PAR2 siRNA was shown to prevent the
      suppression  of Cx26 induced by Der p 1 in BEAS-2B cells. CONCLUSION: The
      suppression of Cx26 in HDM-sensitized AR patients is related to a PAR2-mediated
      pathway and might serve during the initiation and maintenance of AR. Targeting
      the PAR2-mediated Cx26 suppression may be a potential  means of preventing
      allergic sensitization.

PMID- 22391068
TI  - The role of nitrosative stress in the pathogenesis of unexplained chronic cough
      with cough hypersensitivity.
AB  - BACKGROUND: Unexplained chronic cough is a common condition without specific
      causes. A hyperreactivity of the cough reflex has been suggested as a mechanism
      for inducing chronic cough. We hypothesized that nitrosative stress in the upper
      airway might play a role in cough  hypersensitivity by causing neurochemical
      abnormalities. METHODS: Fifty-one patients with unexplained chronic cough and 27
      controls were enrolled. A capsaicin cough provocation test was performed to
      determine cough sensitivity. Nitrosative stress in the upper airway was  assessed
      by quantifying 3-nitrotyrosine (3-NT) immunostaining in nasal epithelial cells
      (NECs) and measuring nasal nitric oxide (nNO). The effect of NO on airway
      epithelium was investigated by measuring the levels of substance P (SP) in nasal
      lavage fluid and evaluating SP expression in airway  epithelial cells. RESULTS:
      Based on the results of the capsaicin test, patients were divided into two
      groups: a cough hypersensitivity (CHS) group and a normal cough sensitivity (NCS)
      group. The levels of 3-NT immunoreactivity in NECs were significantly higher in
      CHS (49  +/- 2.9%) than in NCS (27 +/- 3.3%) and controls (12 +/- 1.6%), a
      pattern that was also reflected in the values of nNO (350 +/- 43, 215 +/- 23, and
      138 +/- 23 ppb in CHS, NCS, and controls, respectively). SP concentration was
      also elevated in nasal lavage fluids  from CHS (746 +/- 28 pg/mL) compared with
      that from NCS (624 +/- 40 pg/mL) and controls (526 +/- 41 pg/mL). SP expression
      in airway epithelial cells was greatly enhanced by exposure to NO donor, which
      was attenuated by pretreatment with either NO scavenger or NO synthase inhibitor.
      CONCLUSION: Increased nitrosative stress in the upper airway may play a role in
      the pathogenesis of unexplained chronic cough with CHS through enhanced secretion
      of SP.

PMID- 22391065
TI  - Acquired cilia dysfunction in chronic rhinosinusitis.
AB  - BACKGROUND: Cilia are complex and powerful cellular structures of the respiratory
      mucosa that play a critical role in airway defense. Respiratory epithelium is
      lined with cilia that perform an integrated and coordinated mechanism called
      mucociliary clearance. Mucociliary  clearance is the process by which cilia
      transport the mucus blanket overlying respiratory mucosa to the gastrointestinal
      tract for ingestion. It is the primary means by which the airway clears
      pathogens, allergens, debris, and toxins. The complex structure and regulatory
      mechanisms that dictate  the form and function of normal cilia are not entirely
      understood, but it is clear that ciliary dysfunction results in impaired
      respiratory defense. METHODS: A literature review of the current knowledge of
      cilia dysfunction in chronic rhinosinsusitis was conducted. RESULTS: Ciliary
      dysfunction may be primary, the result of genetic mutations resulting in abnormal
      cilia structure, or, more commonly, secondary, the result of environmental,
      infectious, or inflammatory stimuli that disrupt normal motility or coordination.
      Patients with chronic  rhinosinusitis (CRS) have been found to have impaired
      mucociliary clearance. Many biochemical, environmental, and mechanical stimuli
      have been shown to influence ciliary beat frequency, and common microbial
      pathogens of respiratory mucosa such as Pseudomonas aeruginosa and Haemophilus
      influenzae  have developed toxins that appear to interrupt normal mucociliary
      function. Furthermore, inflammatory mediators known to be present in patients
      with CRS appear to impair secondarily mucociliary clearance. CONCLUSION: The goal
      of this article is to summarize the recent developments  in the understanding of
      cilia dysfunction and mucociliary clearance in CRS.

PMID- 22391069
TI  - HLA-DRA polymorphisms associated with risk of nasal polyposis in asthmatic
      patients.
AB  - BACKGROUND: Nasal polyps, part of the aspirin triad symptoms, are edematous
      protrusions arising from the mucosa of the nasal sinuses. Although the causative
      factors and pathogenesis of the polyps are unknown, the significant effect of
      human leukocyte antigen-DR (HLA-DR) expression  in nasal polyps and genetic
      associations of the major histocompatibility complex class II, DR alpha (HLA-DRA)
      with immune-mediated diseases have been revealed. METHODS: To investigate the
      associations of HLA-DRA polymorphisms with nasal polyposis in asthmatic  patients
      and in aspirin-hypersensitive subgroups, 22 single nucleotide polymorphisms
      (SNPs) were genotyped in a total of 467 asthmatic patients including 158 nasal
      polyp-positive and 309 polyp-negative subjects. RESULTS: Statistical analysis
      showed that four SNPs (p = 0.0005-0.02;  Pcorr = 0.009-0.033) and one haplotype
      (p = 0.002; Pcorr = 0.029) were significantly associated with the presence of
      nasal polyposis in asthmatic patients. In further analysis, although significant
      signals disappeared after corrections for multiple testing, two HLA-DRA
      polymorphisms  (rs9268644C>A, rs3129878A>C) were found to be potential markers
      for nasal polyp development in aspirin-tolerant asthma (p = 0.005 and 0.007,
      respectively) compared with the aspirin-exacerbated respiratory disease (p >
      0.05) subgroup. In silico analysis predicted  major "C" allele of rs14004C>A in
      5'-untranslated region as a potential binding site for regulatory glucocorticoid
      receptor. In addition, sequence nearby rs1051336G>A is suspected to be a
      pyrimidine-rich element that affects mRNA stability. CONCLUSION: Despite the need
      for replication in larger cohorts and/or functional evaluations, our findings
      suggest that HLA-DRA polymorphisms might contribute to nasal polyposis
      susceptibility in patients with asthma.

PMID- 22391070
TI  - Crenotherapy modulates the expression of proinflammatory cytokines and
      immunoregulatory peptides in nasal secretions of children with chronic
      rhinosinusitis.
AB  - BACKGROUND: The effect of crenotherapy on major mucosal markers of inflammation,
      TNF alpha, human beta-defensins 2 (hBD-2), and calprotectin, are largely
      unexplored in pediatric chronic rhinosinusitis (CRS). The aim of this study was
      to investigate the effects of crenotherapy  with sulfate-sodium-chloride water on
      mucosal markers of inflammation in children with CRS. METHODS: Children with CRS
      received 15-day crenotherapy consisting of sulfate-sodium-chloride thermal water
      inhalations by nasal aerosol (15 minutes/day). Concentrations of nasal  mucosal
      markers of inflammation (TNF alpha, hBD-2, and calprotectin) were measured before
      and after crenotherapy. Presence of specific symptoms (nasal obstruction, nasal
      discharge, facial pain, sense of smell, and cough), value of symptoms score sino
      nasal 5 (SN5), quality of life (QoL) score  (1 [worse] to 10 [optimal]) were also
      assessed. RESULTS: After crenotherapy a significant reduction was observed in TNF
      alpha (from 0.14 +/- 0.02 to 0.08 +/- 0.01; p < 0.001), calprotectin (from 2.9 +/
      1.0 to 1.9 +/- 0.5; p < 9.001), and hBD-2  (from 2.0 +/- 0.1 to 0.9 +/- 0.6; p <
      0.001) concentrations. A significant (p < 0.05) reduction in number of subjects
      presenting symptoms of nasal obstruction (100% versus 40%), nasal discharge (33%
      versus 13%), facial pain (30% versus 10%), and sense of smell (60% versus 20%) 
      was observed. A significant improvement of SN5 (from 3.07 +/- 0.76 to 2.08 +/-
      0.42; p < 0.001) was observed after the crenotherapy. QoL also improved after
      crenotherapy (from 4.2 +/- 1.1 to 6.6 +/- 1.0; p < 0.001). CONCLUSION:
      Crenotherapy induced  a down-regulation of nasal mucosal inflammatory mediators
      in children with CRS.

PMID- 22391071
TI  - Subcutaneous and sublingual immunotherapy for allergic rhinitis: what is the
      evidence?
AB  - BACKGROUND: Increasing interest in sublingual immunotherapy (SLIT) among
      practitioners and patients has resulted in numerous publications and clinical
      trials in recent years. With the clinical growth of SLIT, discussions of its
      efficacy, safety, and immunologic effects have  intensified, as have comparisons
      to subcutaneous immunotherapy (SCIT). In the United States, SCIT has been the
      traditional form of immunotherapy for inhalant allergy and is the only
      immunotherapy method approved by the U.S. Food and Drug Administration at this
      time. The similarities and differences  between SLIT and SCIT are often
      discussed, yet clinical studies directly comparing these immunotherapy methods
      are scarce. METHODS: A literature review of specific issues and controversies
      between SLIT and SCIT for allergic rhinitis was conducted. RESULTS: Safety,
      efficacy, and immunologic effects of these two immunotherapy techniques are
      reviewed. CONCLUSION: Unanswered questions relating to SLIT are examined.

PMID- 22391073
TI  - Diagnosis and treatment of allergic rhinitis due to house-dust mites in Spain.
AB  - BACKGROUND: The prevalence of allergic rhinitis due to house-dust mites (HDMs) is
      high and increasing. Treatment guidelines and consensus statements are available,
      but few data exist on how these are followed in clinical practice in Spain. This
      study was designed to collect  data on diagnosis and treatment of allergic
      rhinitis due to HDMs and adherence to guidelines in Spanish specialized clinical
      practice. METHODS: In this observational study, patients referred to specialists
      for a first consultation were collected. Diagnosis of allergic rhinitis  due to
      HDMs was confirmed by skin-prick tests and measurement of specific immunoglobulin
      E levels. Variables included patient demographics, diagnosis, and treatment.
      Moreover, investigators answered a questionnaire on their attitudes to allergic
      rhinitis treatment. RESULTS: Two hundred forty-seven clinicians collected
      evaluable data from 519 patients (mean age, 24.8 years; SD, 11.9 years; 54%
      women) with confirmed allergic rhinitis (86.2% with moderate or severe disease
      and 70.5% with persistent disease; 40% with concomitant asthma) caused by
      Dermatophagoides.  In 85.6% of patients, symptoms had not improved since
      diagnosis and good disease control was only being achieved in 43.4%. At the study
      visit, pharmacologic treatment was prescribed in 98.3% and allergen immunotherapy
      was prescribed in 52.2% of patients. CONCLUSION: When  patients with HDM-induced
      allergic rhinitis are referred to an allergy specialist in Spain, they have
      moderate-to-severe persistent disease and are generally not achieving good
      control with symptomatic treatment. Allergen immunotherapy is prescribed in
      approximately one-half of patients. In  this representative sample of Spanish
      allergy specialists, the level of adherence to clinical guidelines in these
      patients is encouraging.

PMID- 22391072
TI  - Aspirin-exacerbated respiratory disease in China: a cohort investigation and
      literature review.
AB  - BACKGROUND: Although the prevalence of aspirin-exacerbated respiratory disease
      (AERD) in western populations is high, AERD is rather rare in China, and few
      related studies have been published to date. METHODS: We performed a prospective
      cohort investigation  on the incidence of AERD in patients with chronic
      rhinosinusitis (CRS) in southern China. A literature search of the China Academic
      Journal Network Publishing Database was conducted to obtain an overview of the
      incidence of AERD in the Chinese population, and previous studies on the
      incidence  of AERD were reviewed. RESULTS: We found 2 patients with aspirin
      hypersensitivity among 351 consecutive CRS (309 with nasal polyps [NPs])
      patients, suggesting a rate of 0.57% in the CRS population. Forty-five articles
      about AERD were obtained by Chinese-language literature  searches. In total, 346
      cases of AERD were reported during the past 30 years. CONCLUSION: Given the large
      population of NPs in China, the prevalence of AERD is very low, and this may be
      related to the reduced levels of nasal tissue eosinophilia and subsequent low
      asthma  comorbidity.

PMID- 22391074
TI  - Bilateral sphenopalatine ganglion blockade improves postoperative analgesia after
      endoscopic sinus surgery.
AB  - BACKGROUND: Endoscopic sinus surgery (ESS) is a common procedure preferably done
      with an anesthetic technique ensuring effective postoperative analgesia while
      speeding discharge home. Although anesthesia administered locally in conjunction
      with vasoconstricting agents is  known to minimize intraoperative bleeding, its
      usefulness in providing postoperative analgesia has not been well characterized.
      The results supporting the use of regional anesthesia for sinus surgery have also
      been limited. Using a randomized, double-blinded and placebo-controlled design, 
      we evaluated recovery times, opioid consumption, and nausea and vomiting after
      ESS when patients were randomized to either general anesthesia (GA) alone or with
      regional blockade. METHODS: Subjects were 70 adults scheduled for sinus surgery.
      All participants underwent propofol/remifentanil/nitrous  oxide anesthesia and
      similar intraoperative care. Patients received either GA alone or with
      sphenopalatine ganglion (SPG) blocks in a double-masked study design. Independent
      observers recorded readiness for discharge, incidence of nausea/vomiting, and
      pain scores every 15 minutes until discharge.  Overall opioid use in the recovery
      area was also a secondary end point. Twenty-four hours later, patients were
      called and asked to rate their pain and overall satisfaction with their pain
      control. RESULTS: Block group participants were considered ready for discharge
      after  45 minutes and discharged from the hospital ~40 minutes sooner than GA
      group participants. The block group required less total fentanyl in the recovery
      room than did the GA group. The incidences of nausea and vomiting did not differ
      significantly. Data at 24 hours postoperatively did not  differ significantly
      between groups but trended toward increased satisfaction in the block group. No
      lasting adverse events were observed. CONCLUSION: Regional anesthesia using
      targeted nerve blocks is effective in ESS. The combination of GA and SPG blockade
      appears to  shorten hospital stay and reduce narcotic requirements in the
      recovery area. No demonstrable benefits were observed after 24 hours regarding
      pain management.

PMID- 22391076
TI  - The effects of corticosteroid on tissue lactoferrin in patients with nasal
      polyposis.
AB  - BACKGROUND: Although, lactoferrin (LF) is the second most important antimicrobial
      and anti-inflammatory peptide after lysozyme in upper respiratory tract, little
      is known about its role in chronic rhinosinusitis (CRS). Recent studies
      pronounced that LF levels were significantly  reduced in CRS with nasal polyposis
      (NP) compared with other subgroups. However, effects of systemic corticosteroid
      (CS) treatment, which is currently the main NP treatment modality, and subsequent
      surgical intervention on LF levels are still not known. This study was designed
      to evaluate  the effects of CS treatment and surgical intervention on LF levels
      in patients with NP. METHODS: Patients with inflammatory NP who were scheduled to
      undergo CS treatment and a control group were included in this study. LF levels
      were determined from mucosal samples taken  from both groups, before and after CS
      treatment, and also 1 month after surgical intervention. RESULTS: Twenty-seven
      patients with NP and 14 patients who underwent septoplasty were included in the
      study. Tissue LF levels were significantly lower in the NP group compared  with
      the control group (p = 0.014). Tissue LF levels did not change significantly in
      NP patients after CS treatment. However, a significant reduction in tissue LF was
      detected 1 month after endoscopic sinus surgery. CONCLUSION: Tissue LF
      concentrations significantly decreased  in patients with NP. CS treatment had no
      effect on tissue LF levels, whereas postendoscopic sinus surgery, tissue LF
      levels were getting lower because there was also a reduction in inflammatory load
      (whether from reduction in mucosa surface area or resolution of disease).

PMID- 22391075
TI  - Aspirin-sensitive asthma and upper airway diseases.
AB  - BACKGROUND: Aspirin exacerbated respiratory disease (AERD) consists of nasal
      polyposis, rhinosinusitis, asthma, and aspirin (ASA) sensitivity. OBJECTIVE: This
      article details how to diagnose and treat AERD and describes the procedures
      associated with ASA  challenge and desensitization, benefits associated with ASA
      desensitization, and appropriate doses for treatment. METHODS: Criteria for
      diagnosis of AERD as well as desensitization protocols for oral ASA challenge and
      combined intranasal ketorolac and oral ASA challenge,  are detailed in this
      article based on literature review. RESULTS: AERD requires a multidimensional
      approach to treat the disease given the multiple conditions. With successful ASA
      desensitization and maintenance of ASA administration, all patients are able to
      achieve ASA  tolerance and select patients are able to achieve improvement in
      clinical markers such as global scores and reduction in use of topical and
      systemic corticosteroids.

PMID- 22391077
TI  - IgE reactivity patterns in patients with allergic rhinoconjunctivitis to ragweed
      and mugwort pollens.
AB  - BACKGROUND: Differential diagnosis between ragweed and mugwort pollen allergy
      represents a large clinical problem in areas where both plants are present. The
      aim of this study was to investigate ragweed- and mugwort-sensitized patients to
      identify specific IgE reactivity  profiles. Results were correlated to clinical
      findings such as medical history and health-related quality of life (HRQL).
      METHODS: Seventy-four patients with allergic rhinoconjunctivitis between July and
      October were examined and underwent in vivo tests (skin-prick  test [SPT] and
      nasal provocation). Sera were evaluated for IgE reactivity to mugwort and ragweed
      pollen extracts, major (Art v 1; Amb a 1) and minor (profilin and calcium-binding
      protein) allergens. HRQL was evaluated using a standardized questionnaire.
      RESULTS: Seventy-one  patients revealed positive SPT reactivity against mugwort
      and 60 patients against ragweed extracts. Of these patients, 74 revealed IgE
      antibodies against mugwort extracts, whereas anti-Art v 1 antibodies were
      detectable in 50 individuals. Fifty-five patients showed IgE antibodies against 
      natural ragweed extracts; anti-Amb v 1 antibodies were detected in six cases
      only. Using standardized clinical history and HRQL questionnaires we were not
      able to detect any differences within different reactivity patterns. CONCLUSION:
      Within the investigated population  of 74 weed-allergic patients the prevalence
      of true mugwort and ragweed sensitization can be calculated as 68 and 8%. High
      prevalence of ragweed sensitization when testing with full extracts can be
      explained by cross-reactivity between other weeds, e.g., mugwort rather than
      cosensitization.  Differences in medical history and HRQL between different
      reactivity patterns were not detectable.

PMID- 22391078
TI  - Orally exhaled nitric oxide in patients with seasonal allergic rhinitis during
      natural pollen season.
AB  - BACKGROUND: Nitric oxide (NO) is the endogenous molecule involved in regulatory,
      protective, and defensive mechanisms. Although exhaled NO (ENO) has been used to
      monitor patients with asthma, possible usage of ENO in allergic rhinitis (AR)
      still needs to be evaluated. The  authors wanted to determine the levels of NO
      exhaled orally both out of the pollen season and during the natural pollen
      exposure in patients with AR without asthma. METHODS: Forty-six patients without
      asthma, with seasonal AR (SAR) and 15 healthy, nonreactive, nonatopic  subjects
      as a control group were investigated. ENO, congestion score, and peak nasal
      inspiratory flows (PNIFs) were measured in all subjects 6 weeks before the pollen
      season, at the height of the pollen season, and 6 weeks after the end of the
      pollen season. RESULTS: Patients  with SAR had significantly higher basal ENO
      values compared with healthy control. The number of parts of NO increased in both
      groups during the pollen season but only in AR patients was the increase
      significant compared with the levels before the pollen season. Those with SAR and
      high levels  of NO in exhaled air at the height of the pollen season had
      significantly lower PNIF rates and higher obstruction scores than out of the
      pollen season and in the healthy group. CONCLUSION: Natural exposure may lead to
      an elevation of ENO in the patients with SAR without  asthma. We estimate that
      the increased ENO may result from subclinical allergic inflammation present
      within the lower airways of nonasthmatic patients with SAR.

PMID- 22391081
TI  - Neurochemical characterization of pterygopalatine ganglion branches in humans.
AB  - BACKGROUND: Pterygopalatine ganglion (PPG) branches, seem to be involved in the
      pathophysiology of facial pain. The functions of these branches, including a
      recently discovered orbital branch, are not completely known but could be of
      clinical significance. This study was  designed to characterize PPG branches
      through immunohistochemical stain and study their anatomy, specifically the
      orbital branches. METHODS: In a cadaver study of four specimens, the
      pterygopalatine fossa (PPF) was dissected out of its bony surroundings as a
      tissue block.  Subsequently, cryostat sectioning of these blocks was performed.
      In one specimen the PPF was microscopically dissected. Recently discovered neural
      structures were identified, dissected out of the tissue block, and cryosectioned.
      All cryostat sectionings were immunohistochemically stained for  protein gene
      product (PGP) 9.5, nitric oxide synthase (NOS), and tyrosine hydroxylase (TH).
      RESULTS: A recently discovered neural connection between the PPG and the
      ophthalmic nerve could be confirmed and classified as an orbital PPG branch. The
      connection stained throughout  for PGP 9.5 and partially stained for NOS. In
      other orbital branches, both NOS and TH(+) nerve fibers were found. The PPG
      contained NOS(+) cells. TH labeling was also found in nerve fibers running
      through the PPG and the vidian nerve. CONCLUSION: The recently  discovered
      orbital PPG branch is of a mixed parasympathetic and sensory nature. In the other
      orbital branches, sympathetic fibers were shown as well. This knowledge may add
      to understanding the symptomatology and therapies of headache syndromes such as
      nerve block.

PMID- 22391080
TI  - Is there any correlation between the results of skin-prick test and the severity
      of symptoms in allergic rhinitis?
AB  - BACKGROUND: This study was designed to determine whether there is any correlation
      between results of the skin-prick test and the severity of symptoms in allergic
      rhinitis. METHODS: We retrospectively evaluated 150 patients with persistent or
      intermittent  allergic rhinitis confirmed by positive skin tests and scaled from
      1 to 4 according to the size of the wheal. The symptoms including sneezing, nasal
      obstruction, rhinorrhea, and nasal itching were ranked according to their
      severity (0 for no symptoms, 1 for mild, 2 for moderate, and 3 for  severe). We
      investigated the correlation between the skin tests' positivity and symptoms
      score, rhinoconjunctivitis quality-of-life questionnaire (RQLQ), and visual
      analog scale (VAS) scores. RESULTS: Of the 150 patients, 98 had persistent and 52
      had intermittent allergic  rhinitis. Some patients had multiple allergen
      sensitivity. Each skin test group was compared with respect to symptom scores,
      RQLQ, or VAS scores. There was no statistically significant correlation between
      the size of the wheal and symptoms score, RQLQ, or VAS scores. There was also no
      correlation  between the type of allergen and symptoms score. CONCLUSION: The
      skin-prick test can be applied to support the diagnosis of allergic rhinitis, but
      one can not predict the severity of illness by stratifying the size of the skin
      prick test result.

PMID- 22391079
TI  - No mucosal atrophy and reduced inflammatory cells: active-controlled trial with
      yearlong fluticasone furoate nasal spray.
AB  - BACKGROUND: Fluticasone furoate nasal spray (FFNS) and mometasone furoate nasal
      spray (MFNS) are well tolerated and more effective than placebo at relieving the
      symptoms of seasonal and perennial allergic rhinitis. Effects of FFNS on the
      nasal histology have not been previously  reported. This study examines the
      effects of FFNS and MFNS, administered daily for 1 year, on the nasal mucosa in
      subjects with perennial allergic rhinitis. METHODS: Subjects with perennial
      allergic rhinitis were randomized 1:1 to q.d., open-label treatment with FFNS,
      110  MUg, or MFNS, 200 MUg, for 1 year. These groups and a healthy control group
      that did not receive study medication underwent nasal biopsies at baseline and 12
      months. RESULTS: The nasal biopsy population comprised 96 participants (37 using
      FFNS, 42 using MFNS, and 17  healthy controls). Epithelial thickness did not
      change appreciably from baseline to week 52 in any of the groups and mean change
      from baseline did not differ between FFNS and MFNS (least square mean difference,
      -0.001 mm, 95% confidence interval, -0.007, 0.006). Although not tested  for
      significance, improvements over baseline were observed in epithelial histology in
      the FFNS group with more epithelium including intact columnar and ciliated
      epithelial cells. No appreciable change in the percentage of goblet cells was
      established. FFNS and MFNS were associated with decreases  in epithelial and
      subepithelial nasal mucosal eosinophils and basophils from baseline to week 52.
      The percentage of subjects with no inflammatory cells at week 52 was 49 and 33%
      for eosinophils and 46 and 24% for basophils, for FFNS and MFNS, respectively.
      CONCLUSION: Yearlong  therapy with either FFNS or MFNS showed no changes in
      epithelial thickness or the percentage of goblet cells as well as a reduction in
      inflammatory cell infiltrate. FFNS was associated with improvements in epithelial
      histology. These data support the long-term safety of FFNS in subjects with 
      perennial allergic rhinitis.

PMID- 22391082
TI  - Usefulness of the subjective cold hyperresponsiveness scale as evaluated by cold
      dry air provocation.
AB  - BACKGROUND: There is still no study about the correlation between the symptom
      score and the reactivity to cold dry air (CDA). The authors developed a
      subjective cold hyperresponsiveness (SCH) scale for CDA and we evaluated its
      usefulness by comparing the changes of the symptom  score and the acoustic
      parameters between different SCH groups and analyzing the correlation between the
      SCH scale and other parameters. METHODS: One hundred fifty-two patients were
      classified according to their SCH scale. The symptom score by the visual analog
      scale (VAS),  the total nasal volume (TNV), and the minimal cross-sectional area
      (MCA) by acoustic rhinometry were obtained before and after CDA provocation.
      Changes of these values were compared between groups and an analysis was
      performed for the correlation between SCH scale and change of the VAS, TNV,  or
      MCA. RESULTS: The patients with SCH grade 2 or 3 had a greater change of the VAS
      scores for nasal obstruction and rhinorrhea. The patients with SCH grade 2 or 3
      had a greater change of the TNV (grade 0, 26.1 +/- 17.2%; grade 1, 33.3 +/-
      26.5%, versus grade  2, 44.2 +/- 30.0%; grade 3, 61.6 +/- 40.0%; p < 0.05) and
      MCA (grade 0, 23.0 +/- 25.3%; grade 1, 35.7 +/- 51.1%, versus grade 2, 61.2 +/-
      72.4%; grade 3, 80.5 +/- 56.4%; p < 0.05). Significant correlation existed
      between the SCH scale and changes in the  TNV or MCA. CONCLUSION: We developed
      the SCH scale and proved its usefulness for evaluating nonspecific
      hyperreactivity.

PMID- 22391083
TI  - Cytologic alterations in nasal mucosa after sphenopalatine artery ligation in
      patients with vasomotor rhinitis.
AB  - BACKGROUND: Vasomotor rhinitis (VR) seems to be related to an imbalance between
      cholinergic and adrenergic activity in the autonomic nervous system. The nerve
      fibers of the sympathetic and parasympathetic nervous systems reach the nose
      through the posterior nasal nerve, which,  after crossing the sphenopalatine
      foramen, distributes to the mucosa following the branches of the sphenopalatine
      vessels. This study was designed to evaluate the effect of sphenopalatine artery
      ligation on nasal function and nasal cytology in patients with VR. METHODS:
      Thirty  patients with VR and bilateral inferior turbinate hypertrophy (ITH) were
      randomly assigned to receive endoscopic inferior turbinoplasty either with or
      without sphenopalatine artery ligation. Pre- (baseline) and postsurgical (1-year
      follow-up) assessment included fiber endoscopy, active anterior  rhinomanometry,
      measurement of mucociliary transport time (MTt), and nasal cytology examination.
      RESULTS: At 1-year follow-up there was a statistically significant improvement in
      nasal resistances in both groups but not on intergroup comparison; MTt
      significantly decreased  in both groups (p < 0.01) and was significantly better
      (p < 0.05) in the group that had undergone sphenopalatine artery ligation. Among
      the patients in this group, significantly fewer were found to have altered
      ciliated cells (p < 0.005) or a hyperchromatic supranuclear stria (p <  0.005) on
      nasal cytology; the differences were statistically significant also on intergroup
      comparison (p < 0.005 and p < 0.001, respectively). CONCLUSION: In patients with
      vasomotor rhinopathy and ITH, improvement in symptoms, nasal resistance, ciliated
      cell trophism,  and MTt was observed after sphenopalatine artery ligation.

PMID- 22391084
TI  - Management of intractable spontaneous epistaxis.
AB  - BACKGROUND: Epistaxis is a common otolaryngology emergency and is often
      controlled with first-line interventions such as cautery, hemostatic agents, or
      anterior nasal packing. A subset of patients will continue to bleed and require
      more aggressive therapy. METHODS: Intractable spontaneous epistaxis was
      traditionally managed with posterior nasal packing and prolonged hospital
      admission. In an effort to reduce patient morbidity and shorten hospital stay,
      surgical and endovascular techniques have gained popularity. A literature review
      was conducted. RESULTS: Transnasal endoscopic sphenopalatine artery ligation and
      arterial embolization provide excellent control rates but the decision to choose
      one over the other can be challenging. The role of transnasal endoscopic anterior
      ethmoid artery ligation is unclear but may be  considered in certain cases when
      bleeding localizes to the ethmoid region. CONCLUSION: This article will focus on
      the management of intractable spontaneous epistaxis and discuss the role of
      endoscopic arterial ligation and embolization as it pertains to this challenging 
      clinical scenario.

PMID- 22391085
TI  - Technological innovations in tissue removal during rhinologic surgery.
AB  - BACKGROUND: The modern rhinologist has a wide variety of technological
      innovations at his/her disposal for the removal of soft tissue and bone during
      endoscopic surgery. We identified and critically evaluated four leading tissue
      removal technologies that have impacted, or  are poised to impact, rhinological
      surgery. METHODS: A literature review was conducted. RESULTS: Technological
      functions, strengths and limitations of microdebriders, radio frequency ablation,
      endoscopic drills, and ultrasonic aspirators were explored.  The primary drawback
      of powered instruments continues to be the higher costs associated with their
      use, and their main advantage is the ability to accomplish multiple functions
      such as tissue removal, suction, and irrigation, all with one tool. The effective
      and safe use of any powered instrument  requires an intimate understanding of its
      function, capabilities, and limitations. CONCLUSION: Powered instrumentation
      continues to play a significant and evolving role in soft tissue and bone removal
      during rhinologic surgery.

PMID- 22391087
TI  - Global and disease-specific health-related quality of life after complete
      endoscopic resection of anterior skull base neoplasms.
AB  - BACKGROUND: Minimally invasive surgery for neoplasms of the anterior skull base
      has revolutionized the treatment of these diseases. The relative effect of
      endoscopic procedures, however, has not been described in terms of disease
      specific and global health-related quality  of life (QoL). METHODS: A single
      center longitudinal study was performed of patients undergoing complete
      endoscopic resection of anterior skull base neoplasms. Patients presenting
      between October 2009 and September 2010 were enrolled. QoL assessments were based
      on the 22-question  Sinonasal Outcomes Test (SNOT-22), Health Utilities Index
      Mark II (HUI-2), and Short-Form 12 (SF-12) and were completed preoperatively and
      at 3, 6, and 12 months postoperatively. Comparisons over time were made within
      subjects. RESULTS: Fourteen patients were enrolled;  11 completed preoperative
      and postoperative assessments (79%). Our cohort consisted of five men and six
      women; mean age was 55 years. Six patients had malignant tumors; four required
      adjuvant therapy. SNOT-22 scores were stable or improved in 10 cases (91%), with
      a significant difference for  the cohort (mean, -33 points; p < 0.01). Ten (91%)
      patients had stable or improved HUI-2 scores (mean utility change, +0.13). SF-12
      scores were stable for both mental (p = 0.17) and physical (p = 0.26) components.
      Mean quality-adjusted life year gain over the study period was 0.07. CONCLUSION:
      Complete endoscopic resection of anterior skull base neoplasms is oncologically
      sound with anecdotal QoL improvements relative to open craniofacial resection. We
      show positive, quantifiable QoL results with validated global and disease
      specific instruments. Additional  work will help to improve outcomes in this
      population and will be used in formal cost-effectiveness analysis.

PMID- 22391089
TI  - Mycobacterium tuberculosis-induced neutrophil ectosomes decrease macrophage
      activation.
AB  - BACKGROUND: The existence of ectosome-like microvesicles released by neutrophils
      was proposed a few decades ago. Other studies revealed that the innate immune
      response during mycobacterial infection is accompanied by an intense migration of
      neutrophils to the site of infection, which may be important during the acute
      phase of tuberculosis. We found that the ectosomes derived from infected
      neutrophils are biologically active and can influence the survival of
      Mycobacterium tuberculosis within macrophages. METHODS: Mycobacteria were
      cultured on supplemented Middlebrook-7H9 broth. All strains were grown to the
      exponential phase and quantitated by serial dilution. Human neutrophils and
      macrophages were infected with mycobacteria. Ectosomes from neutrophils were
      isolated post-infection and characterized by transmission electron microscopy and
      flow cytometry. To determine whether these microvesicles influenced
      mycobactericidal activity, mycobacteria-infected macrophages were treated with
      isolated ectosomes. RESULTS: Ectosomes were released from neutrophils infected
      with mycobacteria. These ectosomes were derived from neutrophil plasma membrane
      and a small proportion stained with PKH26. These microvesicles, when incubated
      with infected macrophages, influenced antimycobacterial activity. CONCLUSIONS:
      This is the first study to demonstrate that ectosomes that are shed from infected
      neutrophils influence mycobactericidal activity in macrophages in vitro,
      suggesting that these microvesicles have biological significance. Nevertheless,
      major gaps in our knowledge of microvesicle biology remain.

PMID- 22391086
TI  - Extensive surgical and comprehensive postoperative medical management for cystic
      fibrosis chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis has a major impact on the quality of life of
      patients with cystic fibrosis (CF) and may contribute to progression of chronic
      lung disease. Despite multiple sinus surgeries, maxillary sinus involvement is a
      recurrent problem. The modified  endoscopic medial maxillectomy (MEMM) permits
      debridement in the clinic, improves mucus clearance with nasal irrigations, and
      increases access for topical delivery of therapeutics. However, clinical outcomes
      of aggressive sinus surgery with regimented postoperative medical treatment have
      not  been systematically evaluated. METHODS: CF patients completed the 22-Item
      Sinonasal Outcome Test questionnaires before sinus surgery (and bilateral MEMM)
      and at sequential postoperative visits. Objective measures included Lund-Kennedy
      endoscopic score and pulmonary function  tests (forced expiratory volume at 1
      second percent [FEV(1)%] predicted). Culture-directed antibiotic therapy,
      prednisone, and topical irrigations were initiated postoperatively. RESULTS:
      Twenty-two patients (mean age, 26.5 years; 4.9 prior sinus operations) underwent 
      MEMM and sinus surgery. Symptom scores were significantly reduced at 60 days
      (primary outcome, 64.7 +/- 18.4 presurgery versus 27.5 +/- 15.3 postsurgery; p <
      0.0001) and up to a year postoperatively (27.6 +/- 12.6; p < 0.0001). Endoscopic
      scores were also reduced after  surgery (10.4 +/- 1.1 presurgery versus 5.7 +/-
      2.4 [30 days], 5.7 +/- 1.4 [60 days], 5.8 +/- 1.3 [120 days], and 6.0 +/- 1.1 [1
      year]; p < 0.0001)]. There were no differences in FEV(1)% predicted up to 1 year
      postoperatively, but hospital admissions secondary  to pulmonary exacerbations
      significantly decreased (2.0 +/- 1.4 versus 3.2 +/- 2.4, respectively; p < 0.05).
      CONCLUSION: Prospective evaluation indicates sinus surgery with MEMM is
      associated with marked improvement in sinus disease outcomes. Additional studies 
      are necessary to confirm whether this treatment paradigm is associated with
      improved CF pulmonary disease.

PMID- 22391090
TI  - Macrophage immunomodulatory activity of extracellular polysaccharide (PEP) of
      Antarctic bacterium Pseudoaltermonas sp.S-5.
AB  - Antarctic bacteria are a novel source of polysaccharides which might have
      potential applications as biological response modifiers (BRM). A
      heteropolysaccharide (PEP) was isolated from the liquid culture broth of the
      Antarctic bacterium Pseudoaltermonas sp.S-5. PEP contained Mannose, Glucose, and
      Galactose in a ratio of 4.8:50.9:44.3. High performance gel permeation
      chromatography of this polysaccharide showed a unimodal profile, and the
      molecular weight was 397 kDa. PEP was studied for its immunological effects on
      peritoneal macrophage cells. Morphological alterations were observed in
      macrophages treated with PEP. In vitro exposure to PEP increased the occurrence
      of activated macrophages and endocytic index in a dose-dependent pattern (2.5-50
      MUg/ml) after 24h of incubation, since increase of 136% and 133% was detected in
      the activated macrophage percentage and endocytic index respectively compared to
      untreated cells. At 200 MUg/ml PEP caused a greatest increase (44.5%) in NO
      production when compared to the control group; however, this polysaccharide did
      not affect respiratory burst in the absence of PMA. Furthermore, it was
      demonstrated that PEP induces macrophages to secrete tumor necrosis factor (TNF)
      alpha and interleukin (IL)-1beta. These results suggested that PEP from
      Pseudoaltermonas sp.S-5 can be classified as a BRM.

PMID- 22391091
TI  - Automatic computer-aided detection of prostate cancer based on multiparametric
      magnetic resonance image analysis.
AB  - In this paper, a fully automatic computer-aided detection (CAD) method is
      proposed for the detection of prostate cancer. The CAD method consists of
      multiple sequential steps in order to detect locations that are suspicious for
      prostate cancer. In the initial stage, a voxel classification is performed using
      a Hessian-based blob detection algorithm at multiple scales on an apparent
      diffusion coefficient map. Next, a parametric multi-object segmentation method is
      applied and the resulting segmentation is used as a mask to restrict the
      candidate detection to the prostate. The remaining candidates are characterized
      by performing histogram analysis on multiparametric MR images. The resulting
      feature set is summarized into a malignancy likelihood by a supervised classifier
      in a two-stage classification approach. The detection performance for prostate
      cancer was tested on a screening population of 200 consecutive patients and
      evaluated using the free response operating characteristic methodology. The
      results show that the CAD method obtained sensitivities of 0.41, 0.65 and 0.74 at
      false positive (FP) levels of 1, 3 and 5 per patient, respectively. In
      conclusion, this study showed that it is feasible to automatically detect
      prostate cancer at a FP rate lower than systematic biopsy. The CAD method may
      assist the radiologist to detect prostate cancer locations and could potentially
      guide biopsy towards the most aggressive part of the tumour.

PMID- 22391094
TI  - Euchromatic and heterochromatic compositional properties emerging from the
      analysis of Solanum lycopersicum BAC sequences.
AB  - The consortium responsible for the sequencing of the tomato (Solanum
      lycopersicum) genome initially focused on the sequencing of the euchromatic
      regions using a BAC-by-BAC strategy. We analyzed the compositional features of
      the whole collection of BAC sequences publically available. This analysis
      highlights specific peculiarities of heterochromatic and euchromatic BACs, in
      particular: the whole BAC collection has i) a large variability in repeat and
      gene content, ii) a positive and significant correlation of LTR retrotransposons
      of the Gypsy class with the repeat content and iii) the preferential location of
      the SINEs (short interspersed nuclear elements) in BAC sequences showing a low
      repeat content. Our results point out a typical design of the tomato chromosomes
      and pave the way for further investigations on the relationship between DNA
      primary structure and chromatin organization in Solanaceae genomes.

PMID- 22391093
TI  - Functional study of the novel multidrug efflux pump KexD from Klebsiella
      pneumoniae.
AB  - We cloned a gene, kexD, that provides a multidrug-resistant phenotype from
      multidrug-resistant Klebsiella pneumoniae MGH78578. The deduced amino acid
      sequence of KexD is similar to that of the inner membrane protein, RND-type
      multidrug efflux pump. Introduction of the kexD gene into Escherichia coli KAM32
      resulted in a MIC that was higher for erythromycin, novobiocin, rhodamine 6G,
      tetraphenylphosphonium chloride, and ethidium bromide than that of the control.
      Intracellular ethidium bromide levels in E. coli cells carrying the kexD gene
      were lower than that in the control cells under energized conditions, suggesting
      that KexD is a component of an energy-dependent efflux pump. RND-type pumps
      typically consist of three components: an inner membrane protein, a periplasmic
      protein, and an outer membrane protein. We discovered that KexD functions with a
      periplasmic protein, AcrA, from E. coli and K. pneumoniae, but not with the
      periplasmic proteins KexA and KexG from K. pneumoniae. KexD was able to utilize
      either TolC of E. coli or KocC of K. pneumoniae as an outer membrane component.
      kexD mRNA was not detected in K. pneumoniae MGH78578 or ATCC10031. We isolated
      erythromycin-resistant mutants from K. pneumoniae ATCC10031, and some showed a
      multidrug-resistant phenotype similar to the drug resistance pattern of KexD. Two
      strains of multidrug-resistant mutants were investigated for kexD expression;
      kexD mRNA levels were increased in these strains. We conclude that changing kexD
      expression can contribute to the occurrence of multidrug-resistant K. pneumoniae.

PMID- 22391092
TI  - DNA adenine methyltransferase (Dam) controls the expression of the cytotoxic
      enterotoxin (act) gene of Aeromonas hydrophila via tRNA modifying enzyme-glucose
      inhibited division protein (GidA).
AB  - Aeromonas hydrophila is both a human and animal pathogen, and the cytotoxic
      enterotoxin (Act) is a crucial virulence factor of this bacterium because of its
      associated hemolytic, cytotoxic, and enterotoxic activities. Previously, to
      define the role of some regulatory genes in modulating Act production, we showed
      that deletion of a glucose-inhibited division gene (gidA) encoding tRNA methylase
      reduced Act levels, while overproduction of DNA adenine methyltransferase (Dam)
      led to a concomitant increase in Act-associated biological activities of a
      diarrheal isolate SSU of A. hydrophila. Importantly, there are multiple GATC
      binding sites for Dam within an upstream sequence of the gidA gene and one such
      target site in the act gene upstream region. We showed the dam gene to be
      essential for the viability of A. hydrophila SSU, and, therefore, to better
      understand the interaction of the encoding genes, Dam and GidA, in act gene
      regulation, we constructed a gidA in-frame deletion mutant of Escherichia coli
      GM28 (dam(+)) and GM33 (?dam) strains. We then tested the expressional activity
      of the act and gidA genes by using a promoterless pGlow-TOPO vector containing a
      reporter green fluorescent protein (GFP). Our data indicated that in GidA(+)
      strains of E. coli, constitutive methylation of the GATC site(s) by Dam
      negatively regulated act and gidA gene expression as measured by GFP production.
      However, in the ?gidA strains, irrespective of the presence or absence of
      constitutively active Dam, we did not observe any alteration in the expression of
      the act gene signifying the role of GidA in positively regulating Act production.
      To determine the exact mechanism of how Dam and GidA influence Act, a real-time
      quantitative PCR (RT-qPCR) assay was performed. The analysis indicated an
      increase in gidA and act gene expression in the A. hydrophila Dam-overproducing
      strain, and these data matched with Act production in the E. coli GM28 strain.
      Thus, the extent of DNA methylation caused by constitutive versus overproduction
      of Dam, as well as possible conformation of DNA influence the expression of act
      and gidA genes in A. hydrophila SSU. Our results indicate that the act gene is
      under the control of both Dam and GidA modification methylases, and Dam regulates
      Act production via GidA.

PMID- 22391095
TI  - Isolation and characteristics of the melanocortin 1 receptor gene (MC1R) in the
      Chinese yakow (Bos grunniens*Bos taurus).
AB  - The Chinese yakow is the offspring of yak (Bos grunniens) and Yellow cattle (Bos
      taurus). The melanocortin 1receptor gene (MC1R) plays a crucial role in
      determining coat colour of mammals. To investigate the relationship of
      polymorphism of the MC1R with coat colour in the Chinese yakow, the coding
      sequence (CDS) and the flanking region of MC1R were sequenced from 84 Chinese
      yakow samples and compared with the sequences of the MC1R from other bovid
      species. A fragment of 1134 base pair (bp) sequences including the full CDS
      (954bp) and parts of the 5'- and 3'-untranslated regions (162 and 18bp,
      respectively) of the Chineseyakow MC1R were obtained. A total of 13 single
      nucleotide polymorphisms (SNPs) including 4 SNPs (T-129C, A-127C, C-106T, G-1A)
      in the 5'-untranslated region and 9 SNPs (C201T, T206C, C340A, C375T, T663C,
      G714C, C870T, G871A and T890C) in the CDS were identified, revealing high genetic
      variability. Four novel SNPs including T206C, G714C, C870T and T890C, which have
      not been reported previously in bovid species, were retrieved. Within 9 coding
      SNPs, C201T, C375T, T663C and C870T were silent mutations, while T206C, C340A,
      G714C, G871A and T890C were mis-sense mutations, corresponding to amino acid
      changes p.L69P, p.Q114K, p.K238N, p.A291N and p.I297T, respectively. Amino acid
      sequences alignment showed a more than 96% similarity with other ruminates.
      However, three classical bovine MC1R loci the E(D), E(+) and e were not retrieved
      in the Chinese yakow, indicating other genes or factors could be involved in
      affecting coat colour in this species.

PMID- 22391096
TI  - Bone mineral density and polymorphisms in metallothionein 1A and 2A in a Chinese
      population exposed to cadmium.
AB  - Cadmium (Cd) effect on bone varies between individuals. We investigated whether
      genetic variation in metallothionein (MT)1A and MT2A associated with Cd induced
      bone loss in this study. A total of 465 persons (311 women and 154 men), living
      in control, moderately and heavily polluted areas, participated. The participants
      completed a questionnaire and the bone mineral density (BMD) was measured by dual
      energy x-ray absorptiometry (DXA) at the proximal radius and ulna. Samples of
      urine and blood were collected for determination of Cd in urine (UCd) and blood
      (BCd). Genotypes for polymorphisms in MT1A (rs11076161) and MT2A (rs10636) were
      determined by Taqman allelic discrimination assays. BCd had a weak association
      with variant alleles for MT1A (rs11076161) and MT2A (rs10636) in female living in
      the highly polluted group (p=0.08 and 0.05, respectively). A weak association was
      found between bone mineral density and MT2A polymorphisms variation (p=0.06) in
      female living in the highly polluted group. Only a weak association was found
      between bone mineral density and MT1A polymorphisms variation in female. Genetic
      variation in the MT1A and MT2A genes may not associate with bone loss caused by
      cadmium exposure.

PMID- 22391097
TI  - Use of iron oxide nanomaterials in wastewater treatment: a review.
AB  - Nowadays there is a continuously increasing worldwide concern for the development
      of wastewater treatment technologies. The utilization of iron oxide nanomaterials
      has received much attention due to their unique properties, such as extremely
      small size, high surface-area-to-volume ratio, surface modifiability, excellent
      magnetic properties and great biocompatibility. A range of environmental clean-up
      technologies have been proposed in wastewater treatment which applied iron oxide
      nanomaterials as nanosorbents and photocatalysts. Moreover, iron oxide based
      immobilization technology for enhanced removal efficiency tends to be an
      innovative research point. This review outlined the latest applications of iron
      oxide nanomaterials in wastewater treatment, and gaps which limited their large
      scale field applications. The outlook for potential applications and further
      challenges, as well as the likely fate of nanomaterials discharged to the
      environment were discussed.

PMID- 22391098
TI  - Molecular architecture of vertebrate kinetochores.
AB  - Kinetochores form a dynamic interface with the microtubules from the mitotic
      spindle to achieve accurate chromosome segregation. Multiple proteins are
      assembled on centromeric DNA to form the kinetochore structure. Recent insights
      regarding the mechanism of kinetochore formation in vertebrate cells have come
      from the identification and characterization of kinetochore proteins using a
      variety of approaches. Constitutive centromere associated network (CCAN) proteins
      create a platform for kinetochore formation. Subsequently, CCAN proteins recruit
      outer kinetochore components such as KNL1, the Mis12 complex and the Ndc80
      complex (KMN network) that attach to the spindle microtubules, together
      comprising the functional kinetochore. In this review, we introduce and discuss
      putative roles of CCAN and KMN proteins during the process of kinetochore
      formation.

PMID- 22391100
TI  - Medium range order of bulk metallic glasses determined by variable resolution
      fluctuation electron microscopy.
AB  - Variable resolution fluctuation electron microscopy (FEM) experiments are
      implemented with hollow-cone dark-field transmission electron microscopy. Medium
      range order lengths of zirconium and iron based bulk metallic glasses and
      amorphous silicon nitride are determined from the FEM results. It shows that
      maximum normalized intensity variances of FEM images occur when their nominal
      resolution approaches the correlation length Lambda of the amorphous materials.
      Additionally, differences in the length and magnitude of medium range order are
      compared between metallic and covalent bond amorphous materials.

PMID- 22391101
TI  - Atom probe study of the carbon distribution in a hardened martensitic hot-work
      tool steel X38CrMoV5-1.
AB  - The microstructure of the hardened common hot-work tool steel X38CrMoV5-1 has
      been characterized by atom probe tomography with the focus on the carbon
      distribution. Samples quenched with technically relevant cooling parameters
      lambda from 0.1 (30 K/s) to 12 (0.25 K/s) have been investigated. The parameter
      lambda is an industrially commonly used exponential cooling parameter,
      representing the cooling time from 800 to 500  degrees C in seconds divided with
      hundred. In all samples pronounced carbon segregation to dislocations and cluster
      formation could be observed after quenching. Carbon enriched interlath films with
      peak carbon levels of 6-10 at.%, which have been identified to be retained
      austenite by TEM, show a thickness increase with increasing lambda. Therefore,
      the fraction of total carbon staying in the austenite grows. This carbon is not
      available for the tempering induced precipitation of secondary carbides in the
      bulk. Through all samples no segregation of any substitutional elements takes
      place. Charpy impact testing and fracture surface analysis of the hardened
      samples reveal the cooling rate induced microstructural distinctions.

PMID- 22391099
TI  - Telomeres: the beginnings and ends of eukaryotic chromosomes.
AB  - The ends of eukaryotic chromosomes are called telomeres. This article provides a
      short history of telomere and telomerase research starting with the pioneering
      work of Muller and McClintock through the molecular era of telomere biology.
      These studies culminated in the 2009 Nobel Prize in Medicine. Critical findings
      that moved the field forward and that suggest directions for future research are
      emphasized.

PMID- 22391102
TI  - The cannabinoid CB1 receptor biphasically modulates motor activity and regulates
      dopamine and glutamate release region dependently.
AB  - Cannabinoid administration modulates both dopaminergic and glutamatergic
      neurotransmission. The present study examines the effects of high and low dose
      WIN55,212-2, a CB1 receptor agonist, on extracellular dopamine and glutamate
      release in vivo via brain microdialysis in the nucleus accumbens (NAc), striatum
      and prefrontal cortex (PFC) in parallel to its effects on locomotor activity.
      WIN55,212-2 increased extracellular dopamine in the NAc (1 mg/kg i.p.), striatum
      (0.1 and 1 mg/kg i.p.) and PFC (1 mg/kg i.p.). Glutamate release was also
      elevated by WIN55,212-2 in the PFC (1 mg/kg i.p.) whereas in the NAc (0.1 and 1
      mg/kg i.p.) and striatum, it was reduced (1 mg/kg i.p.). WIN55,212-2
      administration produced hyperlocomotion at the lower dose (0.1 mg/kg i.p.) and
      hypolocomotion at the higher dose (1 mg/kg i.p.). Co-administration with the CB1
      antagonist, SR-141716A (0.03 mg/kg i.p.), prevented the above effects. According
      to the present results, WIN55,212-2 affected locomotor activity biphasically
      while exerting converging effects on dopamine activity but diverging effects on
      glutamate release between cortical and subcortical regions, especially at the
      higher dose. These findings emphasize the involvement of the CB1 receptor in the
      simultaneous modulation of dopaminergic and glutamatergic neurotransmission in
      brain regions involved in reward and locomotion and suggest possible underlying
      mechanisms of acute cannabinoid exposure and its psychoactive and behavioural
      manifestations.

PMID- 22391103
TI  - Mode of peroxisome proliferator-activated receptor gamma activation by luteolin.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma) is a target for
      treatment of type II diabetes and other conditions. PPARgamma full agonists, such
      as thiazolidinediones (TZDs), are effective insulin sensitizers and anti
      inflammatory agents, but their use is limited by adverse side effects. Luteolin
      is a flavonoid with anti-inflammatory actions that binds PPARgamma but, unlike
      TZDs, does not promote adipocyte differentiation. However, previous reports
      suggested variously that luteolin is a PPARgamma agonist or an antagonist. We
      show that luteolin exhibits weak partial agonist/antagonist activity in
      transfections, inhibits several PPARgamma target genes in 3T3-L1 cells (LPL,
      ORL1, and CEBPalpha) and PPARgamma-dependent adipogenesis, but activates GLUT4 to
      a similar degree as rosiglitazone, implying gene-specific partial agonism. The
      crystal structure of the PPARgamma ligand-binding domain (LBD) reveals that
      luteolin occupies a buried ligand-binding pocket (LBP) but binds an inactive
      PPARgamma LBD conformer and occupies a space near the beta-sheet region far from
      the activation helix (H12), consistent with partial agonist/antagonist actions. A
      single myristic acid molecule simultaneously binds the LBP, suggesting that
      luteolin may cooperate with other ligands to bind PPARgamma, and molecular
      dynamics simulations show that luteolin and myristic acid cooperate to stabilize
      the Omega-loop among H2', H3, and the beta-sheet region. It is noteworthy that
      luteolin strongly suppresses hypertonicity-induced release of the pro
      inflammatory interleukin-8 from human corneal epithelial cells and reverses
      reductions in transepithelial electrical resistance. This effect is PPARgamma
      dependent. We propose that activities of luteolin are related to its singular
      binding mode, that anti-inflammatory activity does not require H12 stabilization,
      and that our structure can be useful in developing safe selective PPARgamma
      modulators.

PMID- 22391104
TI  - Positron emission tomography/computed tomography imaging of residual skull base
      chordoma before radiotherapy using fluoromisonidazole and fluorodeoxyglucose:
      potential consequences for dose painting.
AB  - PURPOSE: To detect the presence of hypoxic tissue, which is known to increase the
      radioresistant phenotype, by its uptake of fluoromisonidazole (18F) (FMISO) using
      hybrid positron emission tomography/computed tomography (PET/CT) imaging, and to
      compare it with the glucose-avid tumor tissue imaged with fluorodeoxyglucose
      (18F) (FDG), in residual postsurgical skull base chordoma scheduled for
      radiotherapy. PATIENTS AND METHODS: Seven patients with incompletely resected
      skull base chordomas were planned for high-dose radiotherapy (dose >=70 Gy). All
      7 patients underwent FDG and FMISO PET/CT. Images were analyzed qualitatively by
      visual examination and semiquantitatively by computing the ratio of the maximal
      standardized uptake value (SUVmax) of the tumor and cerebellum (T/C R), with
      delineation of lesions on conventional imaging. RESULTS: Of the eight lesion
      sites imaged with FDG PET/CT, only one was visible, whereas seven of nine lesions
      were visible on FMISO PET/CT. The median SUVmax in the tumor area was 2.8 g/mL
      (minimum 2.1; maximum 3.5) for FDG and 0.83 g/mL (minimum 0.3; maximum 1.2) for
      FMISO. The T/C R values ranged between 0.30 and 0.63 for FDG (median, 0.41) and
      between 0.75 and 2.20 for FMISO (median,1.59). FMISO T/C R >1 in six lesions
      suggested the presence of hypoxic tissue. There was no correlation between FMISO
      and FDG uptake in individual chordomas (r = 0.18, p = 0.7). CONCLUSION: FMISO
      PET/CT enables imaging of the hypoxic component in residual chordomas. In the
      future, it could help to better define boosted volumes for irradiation and to
      overcome the radioresistance of these lesions. No relationship was founded
      between hypoxia and glucose metabolism in these tumors after initial surgery.

PMID- 22391105
TI  - Interfractional positional variability of fiducial markers and primary tumors in
      locally advanced non-small-cell lung cancer during audiovisual biofeedback
      radiotherapy.
AB  - PURPOSE: To evaluate implanted markers as a surrogate for tumor-based setup
      during image-guided lung cancer radiotherapy with audiovisual biofeedback.
      METHODS AND MATERIALS: Seven patients with locally advanced non-small-cell lung
      cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a
      reference bony structure (vertebra) were contoured for all 10 phases of the four
      dimensional respiration-correlated fan-beam computed tomography and weekly four
      dimensional cone-beam computed tomography. RESULTS: The systematic/random
      interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm
      in the x (lateral), y (anterior-posterior), and z (superior-inferior) directions,
      respectively. The systematic/random interfractional marker-to-bone displacements
      were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The
      systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x,
      y, and z directions, respectively. All displacements changed significantly over
      time (p < 0.0001). CONCLUSIONS: Although marker-based image guidance may decrease
      the risk for geometric miss compared with bony anatomy-based positioning, the
      observed displacements between markers and tumor centroids indicate the need for
      repeated soft tissue imaging, particularly in situations with large tumor volume
      change and large initial marker-to-tumor centroid distance.

PMID- 22391106
TI  - Non-steroidal anti-inflammatory drugs and efficacy of antidepressants in major
      depressive disorder.
AB  - BACKGROUND: It has been proposed that non-steroidal anti-inflammatory drugs
      (NSAIDs) may interfere with the efficacy of antidepressants and contribute to
      treatment resistance in major depressive disorder (MDD). This effect requires
      replication and a test of whether it is specific to serotonin-reuptake inhibiting
      (SRI) antidepressants. METHOD: We tested the effect of concomitant medication
      with NSAIDs on the efficacy of escitalopram, a SRI antidepressant, and
      nortriptyline, a tricyclic antidepressant, among 811 subjects with MDD treated
      for up to 12 weeks in the GENDEP study. Effects of NSAIDs on improvement of
      depressive symptoms were tested in mixed-effect linear models. Effects on
      remission were tested in logistic regression. Age, sex, baseline severity and
      centre of recruitment were considered as potential confounding factors. RESULTS:
      Ten percent (n=78) of subjects were taking NSAIDs during the antidepressant
      treatment. Older subjects were significantly more likely to take NSAIDs. After
      controlling for age, sex, centre of recruitment and baseline severity,
      concomitant medication with NSAIDs did not significantly influence the efficacy
      of escitalopram [beta=0.035, 95% confidence interval (CI) -0.145 to 0.215,
      p=0.704] or nortriptyline (beta=0.075, 95% CI -0.131 to 0.281, p=0.476). Although
      slightly fewer subjects who took NSAIDs reached remission [odds ratio (OR) 0.80,
      95% CI 0.49-1.31, p=0.383], this non-significant effect was reversed after
      controlling for age, sex, baseline severity and recruitment centre effects (OR
      1.04, 95% CI 0.61-1.77, p=0.882). CONCLUSIONS: NSAIDs are unlikely to affect the
      efficacy of SRI or other antidepressants. Concurrent use of NSAIDs and
      antidepressants does not need to be avoided.

PMID- 22391107
TI  - Modified miniplates for orthopaedic skeletal anchorage.

PMID- 22391108
TI  - Reconstruction of the nose with a new double flap technique: microvascular
      osteocutaneous femur and microvascular chondrocutaneous ear flap--first clinical
      results.
AB  - This study describes a new microvascular flap combination from the medial femur
      and ear to reconstruct the nose after subtotal resection and presents the first
      clinical results. In four patients a squamous cell carcinoma of the nose was
      registered. In three patients this was diagnosed for the first time while in the
      fourth patient it was the second relapse after two resections and local flap
      surgery. In every case, tumour resection ended up in an extended defect of the
      nose, cheek and upper lip region. For skeletal reconstruction and the inner
      lining of the nose, a microvascular osteocutaneous femur flap was used. After
      reconstructing the nasal skeleton, the remaining defect was covered by a
      microvascular composite flap from the left ear and preauricular region. Both flap
      pedicles were anastomosed to the facial vein and artery. In every case, the flaps
      healed without complications. There was no tumour relapse. 12 months after
      reconstruction, minor surgical corrections were made. The patients showed a
      satisfying functional and aesthetic result. The combination of a microvascular
      osteocutaneous femur flap and a microvascular ear flap can be used successfully
      for reconstructing the nose after subtotal resection.

PMID- 22391109
TI  - Increased circulating concentrations of bioactive PTH 1-84 in patients with heart
      failure.
AB  - BACKGROUND: PTH is related to left ventricular hypertrophy and its circulating
      levels are associated with worse prognosis in patients with heart failure (HF).
      The objectives of our study were to measure the circulating levels of bioactive
      PTH 1-84 through third-generation assay in HF patients, to determine their
      association with the disease severity as well as their relation with recognized
      biomarkers of HF worsening and prognosis. METHODS: PTH 1-84 concentrations were
      determined in 76 HF patients and in 49 healthy volunteers. Circulating levels of
      amino-terminal proatrial natriuretic peptide (Nt-proANP), B-type natriuretic
      peptide (BNP), Nt-proBNP, proBNP, and big endothelin-1 (Big ET-1) were also
      measured. RESULTS: HF patients had in- creased PTH 1-84 levels in comparison to
      controls. A significant increase of the PTH 1-84 circulating concentrations was
      observed according to the New York Heart Association functional classes. PTH 1-84
      circulating concentrations were also significantly correlated with Nt-proANP,
      BNP, Nt-proBNP, proBNP, and Big ET-1. CONCLUSIONS: PTH 1-84 circulating levels
      are significantly increased in HF patients in comparison to healthy individuals.
      Our study has also demonstrated that circulating concentrations of bioactive PTH
      are related to HF severity and well-established biomarkers of the worsening of
      the disease.

PMID- 22391111
TI  - Repair-oriented categorization of circumcision urethral injury in Benin city,
      Nigeria.
AB  - BACKGROUND: The wide spectrum of circumcision urethral injury/fistula makes
      selection of appropriate repair methods challenging in sub-Saharan Africa. This
      paper reports on the outcome of repair-oriented categorization in a Nigerian
      center. METHODS: Consecutive children presenting with circumcision urethral
      injury/fistula at the University of Benin Teaching Hospital were categorized into
      six repair-oriented groups in 2009-2011. RESULTS: 21 children were treated.
      Except in 2 cases, early neonatal circumcision at an average age of 8 days (range
      4-14 days) had been performed, the majority (52%) by paramedics at home.
      Categories of injury/fistula based on severity ranged from isolated fistula (38%)
      which required fistula excision and repair (category A) to severe ventral
      urethral/coronal/glanular avulsion (29%) which required urethral plate
      tubularization/ventral penile reconstruction (category F). Overall, successful
      first-stage repair was achieved in 19 (91%) children. Meatal stenosis (2),
      urethral stricture (1), which responded to serial dilatation, and minor urinary
      leakage (2), which was closed at second stage, were the post-repair
      complications. Adequate penile size and straight penis on erection were achieved
      in all cases. Cosmetic outcome was excellent in 16 (76%) cases, good in 4 (19%)
      and fair in 1 (5%). CONCLUSION: Repair-oriented categorization, which could be
      useful to practitioners in similar settings, was satisfactory in managing
      urethral injury/urethrocutaneous fistula.

PMID- 22391110
TI  - Downgrading of high-grade vesicoureteral reflux is a reliable option in the
      treatment of children with grade IV-V reflux accompanied by breakthrough
      infections.
AB  - PURPOSE: To evaluate incidence of urinary tract infection (UTI) and natural
      history of downgraded vesicoureteral reflux (VUR) in children with high-grade VUR
      following endoscopic correction. MATERIALS AND METHODS: We retrospectively
      studied 54 children (13 males and 41 females) with a mean age of 1.8 years who
      underwent endoscopic correction of Grade IV-V VUR due to breakthrough infections
      while on antibiotic prophylaxis. Reflux was Grade IV in 40 (74%) and V in 14
      (26%) patients comprising 95 renal refluxing units (RRU). Reflux was corrected in
      72 (76%) RRU. 18 (34%) patients/23 (24%) RRU demonstrated downgrading of VUR. 21
      of the 23 RRU showed Grade II and 2 Grade III VUR, and were taken off antibiotic
      prophylaxis and allocated to observation. Patients were followed for 2-22 years
      (median 14 years). RESULTS: Technetium 99m dimercaptosuccinic acid renal scan
      demonstrated preoperative renal scarring in 21 (78%) of the 23 RRU with
      downgraded VUR. None of the children developed febrile UTI after surgery. 1 RRU
      showed renal function deterioration. 8 (44%) of the 18 patients underwent follow
      up voiding cystourethrogram, and in 7 (88%) there was either spontaneous
      resolution of VUR or downgrade to Grade I VUR. CONCLUSIONS: Downgrading of VUR is
      a reasonable option in patients with high-grade VUR suffering from breakthrough
      infections while on antibiotic prophylaxis. It leads to the cessation of febrile
      UTIs, further spontaneous resolution of VUR and may potentially avoid renal
      damage.

PMID- 22391112
TI  - Should antiplatelet and anticoagulant medications be discontinued before minor
      oral surgery procedures?

PMID- 22391113
TI  - An investigation of the influence of process and formulation variables on
      mechanical properties of high shear granules using design of experiment.
AB  - Being able to predict the properties of granules from the knowledge of the
      process and formulation variables is what most industries are striving for. This
      research uses experimental design to investigate the effect of process variables
      and formulation variables on mechanical properties of pharmaceutical granules
      manufactured from a classical blend of lactose and starch using hydroxypropyl
      cellulose (HPC) as the binder. The process parameters investigated were
      granulation time and impeller speed whilst the formulation variables were starch
      to-lactose ratio and HPC concentration. The granule properties investigated
      include granule packing coefficient and granule strength. The effect of some
      components of the formulation on mechanical properties would also depend on the
      process variables used in granulation process. This implies that by subjecting
      the same formulation to different process conditions results in products with
      different properties.

PMID- 22391114
TI  - Human T(H)2 cells respond to cysteinyl leukotrienes through selective expression
      of cysteinyl leukotriene receptor 1.
AB  - BACKGROUND: Allergic asthma is characterized by reversible airway obstruction and
      bronchial hyperresponsiveness associated with T(H)2 cell-mediated inflammation.
      Cysteinyl leukotrienes (CysLTs) are potent lipid mediators involved in
      bronchoconstriction, mucus secretion, and cell trafficking in asthmatic patients.
      Recent data have implicated CysLTs in the establishment and amplification of
      T(H)2 responses in murine models, although the precise mechanisms are unresolved.
      OBJECTIVES: Preliminary microarray studies suggested that human T(H)2 cells might
      selectively express cysteinyl leukotriene receptor 1 (CYSLTR1) mRNA. We sought to
      establish whether human T(H)2 cells are indeed a CysLT target cell type. METHODS:
      We examined the expression of CYSLTR1 using real-time PCR in human T(H)1 and
      T(H)2 cells. We functionally assessed cysteinyl leukotriene receptor 1 protein
      (CysLT(1)) expression using calcium flux, cyclic AMP, and chemotaxis assays.
      RESULTS: We show that human T(H)2 cells selectively express CYSLTR1 mRNA at high
      levels compared with T(H)1 cells after in vitro differentiation from naive
      precursors. Human T(H)2 cells are selectively responsive to CysLTs in a calcium
      flux assay when compared with T(H)1 cells with a rank order of potency similar to
      that described for CysLT(1) (leukotriene [LT] D(4) > LTC(4) > LTE(4)). We also
      show that LTD(4)-induced signaling in T(H)2 cells is mediated through CysLT(1)
      coupled to G(alpha)q and G(alpha)i proteins, and both pathways can be completely
      inhibited by selective CysLT(1) antagonists. LTD(4) is also found to possess
      potent chemotactic activity for T(H)2 cells at low nanomolar concentrations.
      CONCLUSIONS: These findings suggest a novel mechanism of action for CysLTs in the
      pathogenesis of asthma and provide a potential explanation for the anti
      inflammatory effects of CysLT(1) antagonists.

PMID- 22391116
TI  - Dopamine agonist-induced penile erection and yawning: differential role of D2
      like receptor subtypes and correlation with nitric oxide production in the
      paraventricular nucleus of the hypothalamus of male rats.
AB  - The dopamine D3 preferring agonist pramipexole (50 ng) induced penile erection
      and yawning when injected into the paraventricular nucleus of the hypothalamus of
      male rats, like the mixed D1/D2-like agonist apomorphine (50 ng), while the D4
      agonist PD 168,077 (100 ng), induced penile erection only. These responses lasted
      for 45-60 min and occurred with an increase of NO2- and NO3- concentrations in
      the dialysate obtained from the paraventricular nucleus by intracerebral
      microdialysis. Pramipexole and apomorphine responses were reduced by the D2
      preferring antagonist L-741,626 (5 MUg), but not by the D3 preferring antagonist
      SB-277011A (10 MUg), or the D4 preferring antagonist L-745,870 (5 MUg), injected
      into the PVN before the dopamine agonist. In contrast, PD 168,077 responses were
      reduced by L-745,870, but not by L-741,626 or SB-277011A. Pramipexole,
      apomorphine and PD 168,077 effects were also reduced by the nitric oxide synthase
      inhibitor S-methyl-L-thiocitrulline (20 MUg) and the N-type voltage-dependent
      Ca2+ channels blocker omega-conotoxin (5 ng), given into the paraventricular
      nucleus, and by the oxytocin antagonist d(CH2)5Tyr(Me)2-Orn8-vasotocin (2 MUg),
      given intracerebroventricularly but not into the paraventricular nucleus before
      dopamine agonists. These results suggest that stimulation of D2, but not D3 or D4
      receptors, by pramipexole or apomorphine increases Ca2+ influx in cell bodies of
      oxytocinergic neurons. This increases the production of nitric oxide, which
      activates oxytocinergic neurotransmission in extra-hypothalamic brain areas and
      spinal cord, leading to penile erection and yawning. However, the stimulation of
      D4 receptors by PD 168,077 also increases Ca2+ influx/nitric oxide production
      leading to penile erection, but not yawning.

PMID- 22391115
TI  - MicroRNA signature in patients with eosinophilic esophagitis, reversibility with
      glucocorticoids, and assessment as disease biomarkers.
AB  - BACKGROUND: The role of microRNAs (miRNAs), a key class of regulators of mRNA
      expression and translation, in patients with eosinophilic esophagitis (EoE) has
      not been explored. OBJECTIVE: We aimed to identify miRNAs dysregulated in
      patients with EoE and assess the potential of these miRNAs as disease biomarkers.
      METHODS: Esophageal miRNA expression was profiled in patients with active EoE and
      those with glucocorticoid-induced disease remission. Expression profiles were
      compared with those of healthy control subjects and patients with chronic
      (noneosinophilic) esophagitis. Expression levels of the top differentially
      expressed miRNAs from the plasma of patients with active EoE and patients with
      EoE remission were compared with those of healthy control subjects. RESULTS: EoE
      was associated with 32 differentially regulated miRNAs and was distinguished from
      noneosinophilic forms of esophagitis. The expression levels of the most
      upregulated miRNAs (miR-21 and miR-223) and the most downregulated miRNA (miR
      375) strongly correlated with esophageal eosinophil levels. Bioinformatic
      analysis predicted interplay of miR-21 and miR-223 with key roles in the
      polarization of adaptive immunity and regulation of eosinophilia, and indeed,
      these miRNAs correlated with key elements of the EoE transcriptome. The
      differentially expressed miRNAs were largely reversible in patients who responded
      to glucocorticoid treatment. EoE remission induced a single miRNA (miR-675)
      likely to be involved in DNA methylation. Plasma analysis of the most upregulated
      esophageal miRNAs identified miR-146a, miR-146b, and miR-223 as the most
      differentially expressed miRNAs in the plasma. CONCLUSIONS: We have identified a
      marked dysregulated expression of a select group of miRNAs in patients with EoE
      and defined their reversibility with glucocorticoid treatment and their potential
      value as invasive and noninvasive biomarkers.

PMID- 22391117
TI  - An examination of the effects of subthalamic nucleus inhibition or MU-opioid
      receptor stimulation on food-directed motivation in the non-deprived rat.
AB  - The subthalamic nucleus (STN) serves important functions in regulating movement,
      cognition, and motivation and is connected with cortical and basal ganglia
      circuits that process reward and reinforcement. In order to further examine the
      role of the STN on motivation toward food in non-deprived rats, these experiments
      studied the effects of pharmacological inhibition or MU-opioid receptor
      stimulation of the STN on the 2-h intake of a sweetened fat diet, the amount of
      work exerted to earn sucrose on a progressive ratio 2 (PR-2) schedule of
      reinforcement, and performance on a differential reinforcement of low-rate
      responding (DRL) schedule for sucrose reward. Separate behavioral groups (N=6-9)
      were tested following bilateral inhibition of the STN with the GABA(A) receptor
      agonist muscimol (at 0-5 ng/0.5 MUl/side) or following MU-opioid receptor
      stimulation with the agonist D-Ala2, N-MePhe4, Gly-ol-enkephalin (DAMGO; at 0,
      0.025 or 0.25 MUg/0.5 MUl/side). Although STN inhibition increased ambulatory
      behavior during 2-h feeding sessions, it did not significantly alter intake of
      the sweetened fat diet. STN inhibition also did not affect the breakpoint for
      sucrose pellets during a 1-h PR-2 reinforcement schedule or impact the number of
      reinforcers earned on a 1-h DRL-20s reinforcement schedule in non-deprived rats.
      In contrast, STN MU-opioid receptor stimulation significantly increased feeding
      on the palatable diet and reduced the reinforcers earned on a DRL-20 schedule,
      although DAMGO microinfusions had no effect on PR-2 performance. These data
      suggest that STN inhibition does not enhance incentive motivation for food in the
      absence of food restriction and that STN MU-opioid receptors play an important
      and unique role in motivational processes.

PMID- 22391118
TI  - Which cue to 'want'? Opioid stimulation of central amygdala makes goal-trackers
      show stronger goal-tracking, just as sign-trackers show stronger sign-tracking.
AB  - Pavlovian cues that have been paired with reward can gain incentive salience.
      Drug addicts find drug cues motivationally attractive and binge eaters are
      attracted by food cues. But the level of incentive salience elicited by a cue re
      encounter still varies across time and brain states. In an animal model, cues
      become attractive and 'wanted' in an 'autoshaping' paradigm, where different
      targets of incentive salience emerge for different individuals. Some individuals
      (sign-trackers) find a predictive discrete cue attractive while others find a
      reward contiguous goal cue more attractive (location where reward arrives: goal
      trackers). Here we assessed whether central amygdala mu opioid receptor
      stimulation enhances the phasic incentive salience of the goal-cue for goal
      trackers during moments of predictive cue presence (expressed in both approach
      and consummatory behaviors to goal cue), just as it enhances the attractiveness
      of the predictive cue target for sign-trackers. Using detailed video analysis we
      measured the approaches, nibbles, sniffs, and bites directed at their preferred
      target for both sign-trackers and goal-trackers. We report that DAMGO
      microinjections in central amygdala made goal-trackers, like sign-trackers, show
      phasic increases in appetitive nibbles and sniffs directed at the goal-cue
      expressed selectively whenever the predictive cue was present. This indicates
      enhancement of incentive salience attributed by both goal trackers and sign
      trackers, but attributed in different directions: each to their own target cue.
      For both phenotypes, amygdala opioid stimulation makes the individual's prepotent
      cue into a stronger motivational magnet at phasic moments triggered by a CS that
      predicts the reward UCS.

PMID- 22391120
TI  - 1H NMR-based metabonomic analysis of brain in rats of morphine dependence and
      withdrawal intervention.
AB  - Metabolic consequences of morphine dependence and withdrawal intervention have
      not been well explored. In the present study, the metabolic changes in brain
      hippocampus, nucleus accumbens (NAc), prefrontal cortex (PFC) and striatum of
      rats with morphine dependence and withdrawal intervention were explored by using
      1H nuclear magnetic resonance coupled with principal component analysis, partial
      least squares and orthogonal signal correction analysis. We found that the
      concentrations of neurotransmitters including glutamate, glutamine and gamma
      aminobutyric acid changed differentially in hippocampus, NAc, PFC and striatum
      after repeated morphine treatment. Significant changes were also found in a
      number of cerebral metabolites including N-acetyl aspartate (NAA), lactic acid,
      creatine, myo-inositol and taurine. These findings indicate the profound
      disturbances of energy metabolism, amino acid metabolism and neurotransmitters
      caused by chronic morphine treatment. Interestingly, morphine-induced changes in
      lactic acid, creatine and NAA were clearly reversed by intervention of methadone
      or clonidine. Our study provides a comprehensive understanding of the metabolic
      alteration associated with morphine addiction and withdrawal therapy, which may
      help to develop new pharmacotherapies.

PMID- 22391119
TI  - Improved motor performance in Dyt1 DeltaGAG heterozygous knock-in mice by
      cerebellar Purkinje-cell specific Dyt1 conditional knocking-out.
AB  - Early-onset generalized torsion dystonia (dystonia 1) is an inherited movement
      disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Most
      patients have a 3-base pair deletion (DeltaGAG) in one allele of DYT1,
      corresponding to a loss of a glutamic acid residue (DeltaE) in the C-terminal
      region of the protein. Functional alterations in basal ganglia circuits and the
      cerebellum have been reported in dystonia. Pharmacological manipulations or
      mutations in genes that result in functional alterations of the cerebellum have
      been reported to have dystonic symptoms and have been used as phenotypic rodent
      models. Additionally, structural lesions in the abnormal cerebellar circuits,
      such as cerebellectomy, have therapeutic effects in these models. A previous
      study has shown that the Dyt1 DeltaGAG heterozygous knock-in (KI) mice exhibit
      motor deficits in the beam-walking test. Both Dyt1 DeltaGAG heterozygous knock-in
      (KI) and Dyt1 Purkinje cell-specific knockout (Dyt1 pKO) mice exhibit dendritic
      alterations of cerebellar Purkinje cells. Here, Dyt1 pKO mice exhibited
      significantly less slip numbers in the beam-walking test, suggesting better motor
      performance than control littermates, and normal gait. Furthermore, Dyt1 DeltaGAG
      KI/Dyt1 pKO double mutant mice exhibited significantly lower numbers of slips
      than Dyt1 DeltaGAG heterozygous KI mice, suggesting Purkinje-cell specific
      knockout of Dyt1 wild-type (WT) allele in Dyt1 DeltaGAG heterozygous KI mice
      rescued the motor deficits. The results suggest that molecular lesions of torsinA
      in Purkinje cells by gene therapy or intervening in the signaling pathway
      downstream of the cerebellar Purkinje cells may rescue motor symptoms in dystonia
      1.

PMID- 22391121
TI  - Excitotoxic lesion of the perirhinal cortex impairs spatial working memory in a
      delayed-alternation task.
AB  - The perirhinal cortex (PRh) is strategically located between the neocortex and
      memory-related structures such as the entorhinal cortex and the hippocampal
      formation. The pattern of strong reciprocal connections between these areas,
      together with experimental evidence that PRh damage induces specific memory
      deficits, has placed this cortical region at the center of a growing interest for
      its role in learning and memory mechanisms. The aim of the present study is to
      clarify the involvement of PRh in learning and retention in a novel experimental
      model of spatial working memory, the water T-maze. The data show that pre
      acquisition neurotoxic PRh lesions caused task-learning deficits. This impairment
      was observed during the acquisition phase as well as the retrieval phase. On the
      other hand, a post-acquisition PRh neurotoxic lesion failed to impair the
      acquisition and the retrieval of the water T-maze task performed 32 day after
      lesion. These results suggest a possible key role of PRh in the acquisition but
      not in the retention of a working memory task. Furthermore, these results show
      that the water T-maze may be a suitable learning paradigm to study different
      components of learning and memory.

PMID- 22391122
TI  - An in-depth Monte Carlo study of lateral electron disequilibrium for small fields
      in ultra-low density lung: implications for modern radiation therapy.
AB  - Modern radiation therapy techniques such as intensity-modulated radiation therapy
      (IMRT) and stereotactic body radiation therapy (SBRT) use tightly conformed
      megavoltage x-ray fields to irradiate a tumour within lung tissue. For these
      conditions, lateral electron disequilibrium (LED) may occur, which systematically
      perturbs the dose distribution within tumour and nearby lung tissues. The goal of
      this work is to determine the combination of beam and lung density parameters
      that cause significant LED within and near the tumour. The Monte Carlo code
      DOSXYZnrc (National Research Council of Canada, Ottawa, ON) was used to simulate
      four 20 * 20 * 25 cm(3) water-lung-water slab phantoms, which contained lung
      tissue only, or one of three different centrally located small tumours (sizes: 1
      * 1 * 1, 3 * 3 * 3, 5 * 5 * 5 cm(3)). Dose calculations were performed using
      combinations of six beam energies (Co-60 up to 18 MV), five field sizes (1 * 1
      cm(2) up to 15 * 15 cm(2)), and 12 lung densities (0.001 g cm(-3) up to 1 g cm(
      3)) for a total of 1440 simulations. We developed the relative depth-dose factor
      (RDDF), which can be used to characterize the extent of LED (RDDF <1.0). For RDDF
      <0.7 severe LED occurred, and both lung and tumour dose were drastically reduced.
      For example, a 6 MV (3 * 3 cm(2)) field was used to irradiate a 1 cm(3) tumour
      embedded in lung with ultra-low density of 0.001 g cm(-3) (RDDF = 0.2). Dose in
      up-stream lung and tumour centre were reduced by as much as 80% with respect to
      the water density calculation. These reductions were worse for smaller tumours
      irradiated with high energy beams, small field sizes, and low lung density. In
      conclusion, SBRT trials based on dose calculations in homogeneous tissue are
      misleading as they do not reflect the actual dosimetric effects due to LED.
      Future clinical trials should only use dose calculation engines that can account
      for electron scatter, with special attention given to patients with low lung
      density (i.e. emphysema). In cases where tissue inhomogeneity corrections are
      applied, the nature of the correction used may be inadequate in predicting the
      correct level of LED. In either case, the dose to the tumour is not the
      prescribed dose and clinical response data are uncertain. The new information
      from this study can be used by radiation oncologists who wish to perform advanced
      radiation therapy techniques while avoiding the deleterious predictable
      dosimetric effects of LED.

PMID- 22391123
TI  - Epigenetic biomarkers in prostate cancer: Current and future uses.
AB  - Epigenome alterations are characteristic of nearly all human malignancies and
      include changes in DNA methylation, histone modifications and microRNAs (miRNAs).
      However, what induces these epigenetic alterations in cancer is largely unknown
      and their mechanistic role in prostate tumorigenesis is just beginning to be
      evaluated. Identification of the epigenetic modifications involved in the
      development and progression of prostate cancer will not only identify novel
      therapeutic targets but also prognostic and diagnostic markers. This review will
      focus on the use of epigenetic modifications as biomarkers for prostate cancer.

PMID- 22391124
TI  - Synthesis of lactosylated glycoclusters and inhibition studies with plant and
      human lectins.
AB  - Under microwave activation, the Cu(I)-catalyzed azide-alkyne cycloaddition
      (CuAAC) between an azido-functionalized lactoside and tetra-alkynylated core
      scaffolds (one porphyrin and three topological conformers of calix[4]arenes)
      afforded four lactosylated glycoclusters in high yields. The glycoclusters were
      then evaluated and compared to a monovalent probe as ligands of two lectins: ECA
      from legume plant Erythrina cristagalli and recombinant human galectin-1.
      Micromolar inhibition concentrations and IC(50) values were measured by
      inhibition of hemagglutination (HIA) or enzyme-linked lectin assays (ELLA),
      respectively for these glycoclusters for binding to ECA. A slight binding
      preference was identified for the porphyrin and the 1,3-alternate calixarene
      scaffolds. Similar inhibition studies were performed for galectin-1 by HIA and
      surface plasmon resonance (SPR) analyses. A strong selectivity was observed for
      the porphyrin and cone conformer topologies under HIA experimental conditions but
      these could not be confirmed using SPR analysis. This difference in the
      inhibitory properties based on two techniques confirmed the need for multiple
      complementary analyses for in-depth and accurate analysis of the inhibitory
      properties of multivalent glycoconjugates to multivalent lectins.

PMID- 22391125
TI  - Biochemical and physiological responses of rice (Oryza sativa L.) as influenced
      by Trichoderma harzianum under drought stress.
AB  - Rice is one of the most important food crops drastically affected by drought in
      lowland rice ecosystems. In the present study, the impact of drought tolerant
      isolates of endophytic fungus Trichoderma harzianum on rice response to drought
      was investigated. Out of 43 Trichoderma isolates studied, only five isolates
      viz., Th 56, Th 69, Th 75, Th 82 and Th 89 were selected to be drought tolerant
      as these were able to colonize well on cow dung at low moisture content of 10-20
      percent, though two isolates, Th 56 and Th 75, grew even at 5 percent moisture
      content. Trichoderma-colonized rice seedlings were slower to wilt in response to
      drought. Colonization delayed drought induced changes like stomatal conductance,
      net photosynthesis and leaf greenness. Drought conditions varying from 3 to 9
      days of withholding water led to an increase in the concentration of many stress
      induced metabolites in rice leaves and decrease of MSI, while Trichoderma
      colonization caused a decrease in proline, MDA and H2O2 contents, and increase in
      phenolics concentration and MSI. Among test isolates, Th 56 induced maximum
      drought tolerance as treated plants recorded only 20-40 percent wilting even at 9
      DDS. With or without exposure to drought, colonization by Trichoderma promoted
      seedling growth, with Th 56 giving the most consistent effect. The primary direct
      effect of Trichoderma colonization was promotion of root growth, regardless of
      water status, which caused delay in the drought responses of rice plants.

PMID- 22391126
TI  - Jasmonic acid accumulation and systemic photosynthetic and electrical changes in
      locally burned wild type tomato, ABA-deficient sitiens mutants and sitiens pre
      treated by ABA.
AB  - Burning the terminal leaflet of younger tomato (Lycopersicon esculentum Mill.)
      leaf caused local and systemic changes in the surface electrical potential (SEP)
      and gas exchange (GE) parameters. The local and systemic accumulation of
      endogenous abscisic acid (ABA) and jasmonic acid (JA) was measured 85 min after
      burning. The experiments were conducted with wild type (WT) plants, ABA-deficient
      mutant sitiens (SIT) and ABA pre-treated SIT plants (SITA). First changes in SEP
      were detected within 1.5 min after burning and were followed by a decrease in GE
      parameters within 3-6 min in WT, SIT and SITA plants. GE and SEP time courses of
      SIT were different and wave amplitudes of SEP of SIT were lower compared to WT
      and SITA. ABA content in WT and SITA control plants was similar and substantially
      higher compared to SIT, JA content was similar among WT, SIT and SITA. While
      changes in the ABA content in systemic leaves have not been recorded after
      burning, the systemic JA content was substantially increased in WT and more in
      SIT and SITA. The results suggest that ABA content governs the systemic reaction
      of GE and the SEP shape upon local burning. ABA, JA and SEP participate in
      triggering the GE reaction. The ABA shortage in the SIT in the reaction to
      burning is partly compensated by an enhanced JA accumulation. This JA
      compensation is maintained even in SIT endogenously supplied with ABA. A
      correlation between the systemic JA content and changes in GE parameters or SEP
      was not found.

PMID- 22391127
TI  - Proteomic analysis of early seed development in Pinus massoniana L.
AB  - Understanding seed development is important for large-scale propagation and
      germplasm conservation for the Masson pine. We undertook a proteomic analysis of
      Masson pine seeds during the early stages of embryogenesis. Two-dimensional
      difference gel electrophoresis (2D DIGE) was used to quantify the differences in
      protein expression during early seed development. Using electrospray ionization
      mass spectrometry/mass spectrometry, we identified proteins from 43 gel spots
      that had been excised from preparative "pick" gels. Proteins involved in carbon
      metabolism were identified and were predominantly expressed at higher levels
      during the cleavage polyembryony and columnar embryo stages. Functional
      annotation of one seed protein revealed it involvement in programmed cell death
      and translation of selective mRNAs, which may play an important role in
      subordinate embryo elimination and suspensor degeneration in polyembryonic seed
      gymnosperms. Other identified proteins were associated with protein folding,
      nitrogen metabolism, disease/defense response, and protein storage, synthesis and
      stabilization. The comprehensive protein expression profiles generated by this
      study will provide new insights into the complex developmental process of seed
      development in Masson pine.

PMID- 22391128
TI  - Aluminium long-term stress differently affects photosynthesis in rye genotypes.
AB  - The ability of crops to overcome Al toxicity varies among crop species and
      cultivars. Among the Triticeae genus, rye (Secale cereale) is considered the most
      Al-tolerant species. In the present work, two rye genotypes differing in Al
      tolerance ('Riodeva': Al-sensitive and 'Donkowsky Zlote': Al-tolerant) were
      exposed to 1.11 and 1.85 mM Al during three weeks. Growth, water status and
      photosynthesis related parameters were assessed. After three weeks of Al
      exposure, both genotypes presented similar decrease in leaf growth. Al-induced
      RWC decreased in both genotypes, but was more remarkable in 'Riodeva'. Al
      toxicity induced a decrease in net photosynthetic rate only after three weeks of
      exposure. In 'D. Zlote', A decrease was accompanied by stomatal closure, Chl a
      content and q(p) reduction, but no alterations in RuBisCo or sFBPase activity
      were observed. In 'Riodeva' plants exposed to 1.11 mM Al, A decrease was
      accompanied by C(i)/C(a) increase whereas in plants exposed to 1.85 mM Al
      C(i)/C(a) was not affected. Nevertheless, for both conditions RuBisCo activity
      decreased. A decrease did not limited glucose accumulation in neither of the rye
      genotypes. This study revealed that Al-induced earlier damages in the 'Riodeva'
      genotype, but both genotypes showed long-term high susceptibility to Al.
      Furthermore, the photosynthetic parameters proved to be a good tool to monitor Al
      sensitivity and long-term exposure showed to be crucial to evaluate Al
      sensitivity.

PMID- 22391129
TI  - Sensing endoplasmic reticulum stress by protein kinase RNA-like endoplasmic
      reticulum kinase promotes adaptive mitochondrial DNA biogenesis and cell survival
      via heme oxygenase-1/carbon monoxide activity.
AB  - Endoplasmic reticulum (ER) stress activates the adaptive unfolded protein
      response, allowing cells to recover folding capacity in the organelle. However,
      the overwhelming response to severe damage results in apoptotic cell death.
      Because of the physical proximity between ER and mitochondria, a functional
      interrelationship between these two organelles, including mitochondrial ATP
      production and apoptosis, has been suggested. The adaptive response to ER stress
      includes the maintenance of cellular energetics, which eventually determines cell
      fate. We previously demonstrated that heme oxygenase-1 (HO-1) activity protects
      cells against ER stress in a protein kinase RNA-like endoplasmic reticulum kinase
      (PERK)-dependent pathway. Here, we provide evidence that PERK-mediated induction
      of HO-1 in murine macrophages, RAW264.7, relays ER stress to mitochondrial DNA
      (mtDNA) replication and function. ER stress induced by thapsigargin treatments
      (10-100 nM) resulted in a 2-fold increase in mtDNA contents compared with that in
      the untreated control. HO-1 activity on ER stress is proven to be critical for
      mitochondrial integrity because chemical inhibition (zinc protoporphyrin, 5-20
      MUM) and genetic depletion of HO-1 by small interference RNA transfection
      suppress the activation of transcription factors for mitochondrial biogenesis.
      Carbon monoxide (CO), an enzymatic by-product of HO-1 activity is responsible for
      the function of HO-1. Limited bioavailability of CO by hemoglobin treatment
      triggers cell death with a concomitant decline in ATP production. Approximately
      78.1% of RAW264.7 cells were damaged in the presence of hemoglobin compared with
      the percentage of injured cells (26.9%) under ER stress alone. Mitochondrial
      generation of ATP levels significantly declined when CO availability was limited
      under prolonged ER stress. Taken together, these results suggest that the
      cellular HO-1/CO system conveys ER stress to cell survival signals from
      mitochondria via both the activation of transcriptional factors and functional
      integrity of mtDNA.

PMID- 22391130
TI  - Therapeutic angiogenesis due to balanced single-vector delivery of VEGF and PDGF
      BB.
AB  - Therapeutic angiogenesis by delivery of vascular growth factors is an attractive
      strategy for treating debilitating occlusive vascular diseases, yet clinical
      trials have thus far failed to show efficacy. As a result, limb amputation
      remains a common outcome for muscle ischemia due to severe atherosclerotic
      disease, with an overall incidence of 100 per million people in the United States
      per year. A challenge has been that the angiogenic master regulator vascular
      endothelial growth factor (VEGF) induces dysfunctional vessels, if expressed
      outside of a narrow dosage window. We tested the hypothesis that codelivery of
      platelet-derived growth factor-BB (PDGF-BB), which recruits pericytes, could
      induce normal angiogenesis in skeletal muscle irrespective of VEGF levels.
      Coexpression of VEGF and PDGF-BB encoded by separate vectors in different cells
      or in the same cells only partially corrected aberrant angiogenesis. In marked
      contrast, coexpression of both factors in every cell at a fixed relative level
      via a single bicistronic vector led to robust, uniformly normal angiogenesis,
      even when VEGF expression was high and heterogeneous. Notably, in an ischemic
      hindlimb model, single-vector expression led to efficient growth of collateral
      arteries, revascularization, increased blood flow, and reduced tissue damage.
      Furthermore, these results were confirmed in a clinically applicable gene therapy
      approach by adenoviral-mediated delivery of the bicistronic vector. We conclude
      that coordinated expression of VEGF and PDGF-BB via a single vector constitutes a
      novel strategy for harnessing the potency of VEGF to induce safe and efficacious
      angiogenesis.

PMID- 22391131
TI  - High levels of p110delta PI3K expression in solid tumor cells suppress PTEN
      activity, generating cellular sensitivity to p110delta inhibitors through PTEN
      activation.
AB  - Class IA PI3K isoforms have divergent, nonredundant cell biological roles. In
      untransformed cells and tissues, p110alpha and p110beta are ubiquitously
      expressed, whereas p110delta expression is highly enriched in leukocytes. High
      levels of p110delta expression have been documented in some solid tumor cell
      lines, but the functional role is unknown. This study aimed to elucidate the link
      between elevated expression of p110delta PI3K and cancer. We report that in
      breast and prostate cancer cells that contain leukocyte levels of p110delta,
      p110delta activity dampens the activity of the PTEN tumor suppressor. Indeed,
      inactivation of p110delta in these cells led to PTEN activation, suppression of
      Akt phosphorylation, and inhibition of cell proliferation, with inhibition of
      PTEN activity being able to counterbalance p110delta inactivation. Likewise,
      forced overexpression of p110delta in cells with low p110delta expression reduced
      PTEN activity, resulting in increased Akt phosphorylation. Our data indicate that
      the oncogenic potential of p110delta PI3K overexpression might at least partially
      act through PTEN inactivation, and that p110delta-selective PI3K inhibitors can
      have a dual antitumor mechanism, namely by directly inhibiting p110delta
      signaling and by a broader inhibition of class I PI3K activity through PTEN
      activation. These data may have important implications in the intervention of
      breast cancer.

PMID- 22391132
TI  - P2X3-mediated peripheral sensitization of neuropathic pain in resiniferatoxin
      induced neuropathy.
AB  - Patients suffering from sensory neuropathy due to skin denervation frequently
      have paradoxical manifestations of reduced nociception and neuropathic pain.
      However, there is a lack of satisfactory animal models to investigate these
      phenomena and underlying mechanisms. We developed a mouse system of neuropathy
      induced by resiniferatoxin (RTX), a capsaicin analog, and examined the functional
      significance of P2X3 receptor in neuropathic pain. From day 7 of RTX neuropathy,
      mice displayed mechanical allodynia (p<0.0001) and thermal hypoalgesia
      (p<0.0001). After RTX treatment, dorsal root ganglion (DRG) neurons of the
      peripherin type were depleted (p=0.012), while neurofilament (+) DRG neurons were
      not affected (p=0.62). In addition, RTX caused a shift in neuronal profiles of
      DRG: (1) increased in P2X3 receptor (p=0.0002) and ATF3 (p=0.0006) but (2)
      reduced TRPV1 (p=0.036) and CGRP (p=0.015). The number of P2X3(+)/ATF3(+) neurons
      was linearly correlated with mechanical thresholds (p=0.0017). The peripheral
      expression of P2X3 receptor in dermal nerves was accordingly increased (p=0.016),
      and an intraplantar injection of the P2X3 antagonists, A-317491 and TNP-ATP,
      relieved mechanical allodynia in a dose-dependent manner. In conclusion, RTX
      induced sensory neuropathy with upregulation of P2X3 receptor for peripheral
      sensitization of mechanical allodynia, which provides a new therapeutic target
      for neuropathic pain after skin denervation.

PMID- 22391134
TI  - Trait impulsivity and prefrontal gray matter reductions in cocaine dependent
      individuals.
AB  - BACKGROUND: Impulsivity is thought to play a key role in cocaine addiction onset
      and progression; therefore, we hypothesized that different facets of impulsive
      personality may be significantly associated with brain structural abnormalities
      in cocaine-dependent individuals. METHODS: Thirty-eight cocaine-dependent
      individuals and 38 non-drug using controls completed the UPPS-P scale (measuring
      five different facets of impulsivity: sensation seeking, lack of premeditation,
      lack of perseverance, and positive and negative urgency) and were scanned on a 3T
      MRI scanner. We used whole-brain voxel-based morphometry analyses (VBM) to detect
      differences in gray matter (GM) and white matter (WM) volumes between cocaine
      users and controls, and to measure differences in the way that impulsivity
      relates to GM and WM volumes in cocaine users vs. controls. RESULTS: Cocaine
      dependent individuals had lower GM volumes in a number of sections of the
      orbitofrontal cortex, right inferior frontal gyrus, right insula, left amygdala
      and parahippocampal gyrus, temporal gyrus, and bilateral caudate. They also had
      lower WM volumes in the left inferior and medial frontal gyrus, superior temporal
      gyrus, right anterior cingulate cortex, insula and caudate. There was a positive
      correlation between trait impulsivity and GM volume in the left inferior/middle
      frontal gyrus of cocaine-dependent individuals, a pattern directly opposed to the
      association in controls. Conversely, in cocaine users lack of premeditation was
      negatively correlated with GM volume in the insula and the putamen. CONCLUSIONS:
      Trait impulsivity may influence cocaine dependence by impacting its
      neurobiological underpinnings in frontostriatal systems.

PMID- 22391133
TI  - Computer adaptive testing of liability to addiction: identifying individuals at
      risk.
AB  - BACKGROUND: Employed as a quantitative measure of substance use disorder (SUD)
      risk, the transmissible liability index (TLI) can be useful for detecting youths
      requiring prevention intervention. This study was conducted to develop and
      evaluate a computer adaptive test (CAT) version of the TLI to identifying
      individuals at risk for SUD. METHODS: In the first sample (N=425) of male and
      female subjects were recruited under aegis of the Center for Education and Drug
      Abuse Research in Pittsburgh, PA, USA, having a mean age of 18.8 years. A
      provisional CAT version of the TLI was assessed using simulation procedures. In
      sample 2, twins were recruited at the 2010 Twinsburg Festival in Twinsburg, OH,
      USA. The CAT and paper and pencil (P&P) versions of the TLI were administered to
      276 twin pairs having a mean age of 19.94 years. RESULTS: The simulated CAT
      version of the TLI predicted cannabis use disorder 2 years after initial study
      with 4% less accuracy (72% vs. 68%) than P&P version but with 78% reduction of
      items. In the twin sample, the CAT version predicted alcohol and drug use (OR=1.7
      [2.1], p<.001) with 64% and 65% accuracy (sensitivity=75% [75%] and
      specificity=64% [65%]). CONCLUSIONS: This study demonstrated that the CAT version
      of the TLI is an accurate and efficient measure of risk for SUD. The CAT version
      of the TLI potentially affords the opportunity for efficient screening of risk so
      that timely interventions can be implemented to prevent occurrence of SUDs having
      frequently lifelong consequences.

PMID- 22391135
TI  - In memoriam. Giovanni Faglia (1930-2012).

PMID- 22391136
TI  - The absence of polymorphisms in ADRB3, UCP1, PPARgamma, and ADIPOQ genes protects
      morbid obese patients toward insulin resistance.
AB  - BACKGROUND AND AIMS: The insulin resistance (IR) is a major metabolic impairment
      in severe obesity, a multifactorial disease in which the importance of the effect
      of single nucleotide polymorphisms (SNP) associations in different rather than
      individual genes was established. The aim of this study was to test the
      predictive value of presence/absence of polymorphisms/ variants in beta3
      adrenergic receptor (ADRB3), uncoupling protein 1 (UCP1), peroxisome proliferator
      activated receptor gamma (PPARgamma), and adiponectin (ADIPOQ) genes in
      diagnosing the IR in obesity. SUBJECTS AND METHODS: We studied 112 (40 males, 72
      females) severely obese (body mass index: 48.5+/-7.5 kg/m2) subjects recruited
      from the outpatient obesity clinic of Federico II University Hospital in Naples.
      Genomic DNA was extracted from peripheral leukocytes with a commercial kit. The
      gene polymorphisms Trp64Arg in ADRB3, -3826 A>G in UCP1, Pro12Ala in PPARgamma,
      and c.268G>A, c.331T>C, and c.334C>T in ADIPOQ were characterized by TaqMan assay
      or by direct sequencing (ADIPOQ). RESULTS AND CONCLUSION: Our results demonstrate
      that -3826A>G UCP1 polymorphism is associated with IR in morbid obesity. Further,
      the lack of any polymorphisms, Trp64Arg in ADRB3 and/or -3826 A>G in UCP1 and/or
      Pro12Ala in PPARgamma and/or c.268G>A, c.331T>C and c.334C>T in ADIPOQ, appears a
      useful prognostic factor (NPV=100%) toward the IR onset in these obese patients
      representing a further parameter for an earlier and appropriate therapy.

PMID- 22391137
TI  - Expression of STRBP mRNA in patients with cryptorchidism and Down's syndrome.
AB  - The most frequent defect of the male urogenital tract at birth is cryptorchidism.
      Cryptorchidism causes primitive testicular pathology responsible for infertility.
      Men with Down's syndrome (DS) have an increased risk of cryptorchidism. The
      spermatid perinuclear RNA-binding protein (STRBP) gene codifies a microtubule
      associated RNA-binding protein and it is highly expressed in the testis as well
      as in the brain. At both levels, this gene seems to play a relevant role in the
      regular development of these organs. These observations prompted us to evaluate
      the expression of STRBP mRNA in 5 DS men with cryptorchidism and 5 normal healthy
      men (controls) by quantitative Real Time PCR in peripheral blood leukocytes. We
      found a decreased expression of the STRBP gene in men with DS and cryptorchidism
      compared with controls. This finding suggests that the impaired expression of
      this gene in DS may play a pathogenetic role in the altered brain and testicular
      development in subjects with DS and cryptorchidism.

PMID- 22391138
TI  - Voxel-based morphometric MRI post-processing in MRI-negative focal cortical
      dysplasia followed by simultaneously recorded MEG and stereo-EEG.
AB  - We aim to report on the usefulness of a voxel-based morphometric MRI post
      processing technique in detecting subtle epileptogenic structural lesions. The
      MRI post-processing technique was implemented in a morphometric analysis program
      (MAP), in a 30-year-old male with pharmacoresistant focal epilepsy and negative
      MRI. MAP gray-white matter junction file facilitated the identification of a
      suspicious structural lesion in the right frontal opercular area. The
      electrophysiological data by simultaneously recorded stereo-EEG and MEG confirmed
      the epileptogenicity of the underlying subtle structural abnormality. The patient
      underwent a limited right frontal opercular resection, which completely included
      the area detected by MAP. Surgical pathology revealed focal cortical dysplasia
      (FCD) type IIb. Postoperatively the patient has been seizure-free for 2 years.
      This study demonstrates that MAP has promise in increasing the diagnostic yield
      of MRI reading in challenging patients with "non-lesional" MRIs. The clinical
      relevance and epileptogenicity of MAP abnormalities in patients with epilepsy
      have not been investigated systematically; therefore it is important to confirm
      their pertinence by performing electrophysiological recordings. When confirmed to
      be epileptogenic, such MAP abnormalities may reflect an underlying subtle
      cortical dysplasia whose complete resection can lead to seizure-free outcome.

PMID- 22391139
TI  - Hemodialysis and peritoneal dialysis are associated with similar outcomes for end
      stage renal disease treatment in Canada.
AB  - BACKGROUND: There were 35 265 patients receiving renal replacement therapy in
      Canada at the end of 2007 with 11.0% of patients on peritoneal dialysis (PD) and
      48.9% on hemodialysis (HD) and a remaining 40.1% living with a functioning kidney
      transplant. There are no contemporary studies examining PD survival relative to
      HD in Canada. The objective was to compare survival outcomes for incident
      patients starting on PD as compared to HD in Canada. METHODS: Using data from the
      Canadian Organ Replacement Register, the Cox proportional hazards (PH) model was
      employed to study survival outcomes for patients initiating PD as compared to HD
      in Canada from 1991 to 2004 with follow-up to 31 December 2007. Comparisons of
      outcomes were made between three successive calendar periods: 1991-95, 1996-2000
      and 2001-04 with the relative risk of death of incident patients calculated using
      an intent-to-treat (ITT) analysis with proportional and non-PH models using a
      piecewise exponential survival model to compare adjusted mortality rates.
      RESULTS: In the ITT analysis, overall survival for the entire study period
      favored PD in the first 18 months and HD after 36 months. However, for the 2001
      04 cohort, survival favored PD for the first 2 years and thereafter PD and HD
      were similar. Among female patients > 65 years with diabetes, PD had a 27% higher
      mortality rate. CONCLUSIONS: Overall, HD and PD are associated with similar
      outcomes for end-stage renal disease treatment in Canada.

PMID- 22391141
TI  - Evolutionary tinkering with visual photoreception.
AB  - Eyes have evolved many times, and arthropods and vertebrates share transcription
      factors for early development. Moreover, the photochemistry of vision in all eyes
      employs an opsin and the isomerization of a retinoid from the 11-cis to the all
      trans configuration. The opsins, however, have associated with several different
      G proteins, initiating hyperpolarizing and depolarizing conductance changes at
      the photoreceptor membrane. Beyond these obvious instances of homology, much of
      the evolutionary story is one of tinkering, producing a great variety of
      morphological forms and variation within functional themes. This outcome poses a
      central issue in the convergence of evolutionary and developmental biology: what
      are the heritable features in the later stages of development that give natural
      selection traction in altering phenotypic outcomes? This paper discusses some
      results of evolutionary tinkering where this question arises and, in some cases,
      where the reasons for particular outcomes and the role of adaptation may not be
      understood. Phenotypic features include: the exploitation of microvilli in
      rhabdomeric photoreceptors for detecting the plane of polarized light; different
      instances of retinoid in the visual pigment; examples of the many uses of
      accessory pigments in tuning the spectral sensitivity of photoreceptors;
      selection of opsins in tuning sensitivity in aquatic environments; employing
      either reflection or refraction in the optics of compound eyes; the multiple ways
      of constructing images in compound eyes; and the various ways of regenerating 11
      cis retinals to maintain visual sensitivity. Evolution is an irreversible
      process, but tinkering may recover some lost functions, albeit by new mutational
      routes. There is both elegance and intellectual coherence to the natural
      processes that produce such variety and functional complexity. But marginalizing
      the teaching of evolution in public education is a continuing social and
      political problem that contributes to the reckless capacity of humans to alter
      the planet without trying to understand how nature works.

PMID- 22391140
TI  - The enzyme 4-hydroxy-2-oxoglutarate aldolase is deficient in primary
      hyperoxaluria type 3.
AB  - BACKGROUND: Mutations in the 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene have
      been recently identified in patients with atypical primary hyperoxaluria (PH).
      However, it was not clearly established whether these mutations caused disease
      via loss of function or activation of the gene product. METHODS: Whole-gene
      sequencing of HOGA1 was conducted in 28 unrelated patients with a high clinical
      suspicion of PH and in whom Types 1 and 2 had been excluded. RESULTS: Fifteen
      patients were homozygous or compound heterozygous for mutations in HOGA1. In
      total, seven different mutations were identified including three novel changes: a
      missense mutation, c.107C > T (p.Ala36Val), and two nonsense mutations c.117C > A
      (p.Tyr39X) and c.208C > T (p.Arg70X) as well as the previously documented c.860G
      > T (p.Gly297Val), c.907C > T (p.Arg303Cys) and in-frame c.944_946delAGG
      (p.Glu315del) mutations. The recurrent c.700 + 5G > T splice site mutation in
      intron 5 was most common with a frequency of 67%. Expression studies on hepatic
      messenger RNA demonstrated the pathogenicity of this mutation. CONCLUSIONS: The
      detection of a patient with two novel nonsense mutations within exon 1 of the
      gene, c.117C > A (p.Tyr39X) and c.208C > T (p.Arg70X), provides definitive proof
      that PH Type 3 is due to deficiency of the 4-hydroxy-2-oxoglutarate aldolase
      enzyme.

PMID- 22391143
TI  - "Split them!" smaller item sizes of cookies lead to a decrease in energy intake
      in children.
AB  - OBJECTIVE: Examine the influence of altering the size of snack food (ie, small vs
      large cookies) on short-term energy intake. METHODS: First- and sixth-graders (n
      = 77) participated in a between-subjects experimental design. All participants
      were offered the same gram weight of cookies during an afternoon tea at their
      school. For half of the participants, food was cut in 2 to make the small item
      size. Food intake (number of cookies, gram weight, and energy intake) was
      examined using ANOVA. RESULTS: Decreasing the item size of food led to a decrease
      of 25% in gram weight intake, corresponding to 68 kcal. Appetitive ratings and
      subject and food characteristics had no moderating effect. CONCLUSIONS AND
      IMPLICATIONS: Reducing the item size of food could prove a useful dietary
      prevention strategy based on decreased consumption, aimed at countering obesity
      promoting eating behaviors favored by the easy availability of large food
      portions.

PMID- 22391142
TI  - BAFF/BAFF-R involved in antibodies production of rats with collagen-induced
      arthritis via PI3K-Akt-mTOR signaling and the regulation of paeoniflorin.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniflorin (Pae) is extracted from the root of
      paeonia lactiflora which have attracted attention for anti-rheumatic and immune
      modulating properties. AIM OF THE STUDY: To investigate the role of PI3K/Akt/mTOR
      signaling mediated by BAFF/BAFF-R in antibodies production and the regulation of
      Pae on the signaling pathway in rats with collagen-induced arthritis (CIA).
      MATERIALS AND METHODS: CIA rats were randomly separated into different groups and
      treated with Pae (25, 100mg/kg) from day 18 to day 38 after immunization. The
      effects of Pae on B lymphocytes of CIA rats were evaluated by the levels of BAFF,
      anti-CII antibody, IgA, IgG and IgM, and the expressions of BAFF-R, PI3K, p-Akt
      and mTOR. RESULTS: In CIA rats, the levels of anti-CII antibody, IgA, IgG and IgM
      in serum enhanced, BAFF, BAFF-R, PI3K, p-Akt and mTOR were highly expressed. Pae
      (100mg/kg) obviously decreased arthritis score, relieved ankle and paw swelling,
      improved spleen histopathology in CIA rats, decreased the levels of IgA, IgM, IgG
      and anti-CII antibody, and significantly decreased the expressions of BAFF, BAFF
      R, PI3K, p-Akt and mTOR. CONCLUSION: PI3K/Akt/mTOR signaling mediated by
      BAFF/BAFF-R participates in antibodies production by B lymphocytes of CIA rats.
      Pae had therapeutic effects on rats with CIA. These effects might be relative to
      regulating PI3K/Akt/mTOR signal mediated by BAFF/BAFF-R, and down regulate the
      antibodies production further.

PMID- 22391144
TI  - Implementing clinical supervision for ICU Outreach Nurses: a case study of their
      journey.
AB  - INTRODUCTION: Many health services with Intensive Care Units have developed ward
      liaison programs, managed by Outreach Nurses, to facilitate the transition for
      patients between the intensive care and general wards. This paper reports a case
      study of clinical supervision for two Outreach Nurses as they adapted to their
      new, largely autonomous role in an Australian tertiary hospital. METHOD:
      Individual clinical supervision was provided fortnightly to two Outreach Nurses
      over 12 months by an experienced facilitator, and evaluated using a case study
      methodology. The Outreach Nurses completed a journal that captured their personal
      and professional growth and the supervisor also provided a reflective account. An
      interview was conducted with both Outreach Nurses to evaluate their experiences
      of clinical supervision. FINDINGS: Key themes emerging from all the data sources
      included: respect for clinical supervision and the supervisor; role
      clarification; understanding and dealing with interpersonal issues; dedicated
      time for reflection; facing up to issues and letting them go. CONCLUSION: The
      Outreach Nurses described the personal and professional benefits of clinical
      supervision and highlighted how it was successfully implemented for them in a
      busy clinical environment with limited available resources.

PMID- 22391146
TI  - Depth of cure of resin composites: is the ISO 4049 method suitable for bulk fill
      materials?
AB  - OBJECTIVES: To evaluate if depth of cure D(ISO) determined by the ISO 4049 method
      is accurately reflected with bulk fill materials when compared to depth of cure
      D(new) determined by Vickers microhardness profiles. METHODS: D(ISO) was
      determined according to "ISO 4049; Depth of cure" and resin composite specimens
      (n=6 per group) were prepared of two control materials (Filtek Supreme Plus,
      Filtek Silorane) and four bulk fill materials (Surefil SDR, Venus Bulk Fill,
      Quixfil, Tetric EvoCeram Bulk Fill) and light-cured for either 10s or 20s. For
      D(new), a mold was filled with one of the six resin composites and light-cured
      for either 10 s or 20 s (n=22 per group). The mold was placed under a
      microhardness indentation device and hardness measurements (Vickers hardness,
      VHN) were made at defined distances, beginning at the resin composite that had
      been closest to the light-curing unit (i.e. at the "top") and proceeding toward
      the uncured resin composite (i.e. toward the "bottom"). On the basis of the VHN
      measurements, Vickers hardness profiles were generated for each group. RESULTS:
      D(ISO) varied between 1.76 and 6.49 mm with the bulk fill materials showing the
      highest D(ISO). D(new) varied between 0.2 and 4.0 mm. D(new) was smaller than
      D(ISO) for all resin composites except Filtek Silorane. CONCLUSIONS: For bulk
      fill materials the ISO 4049 method overestimated depth of cure compared to depth
      of cure determined by Vickers hardness profiles.

PMID- 22391145
TI  - Salivary alpha-amylase and cortisol responsiveness following electrical
      stimulation stress in panic disorder patients.
AB  - Psychosocial stress-induced activation of salivary alpha-amylase (sAA) functions
      is as a marker of sympathoadrenal medullary system (SAM) activity. However, in
      contrast to salivary cortisol, sAA has been less extensively studied in panic
      disorder patients. The present study measured sAA and salivary cortisol levels in
      patients with panic disorder following electrical stimulation stress. The authors
      determined Profile of Mood State (POMS) scores and State-Trait anxiety Inventory
      (STAI) scores, heart rate variability (HRV), and levels of sAA and salivary
      cortisol in 34 patients with panic disorder and 41 healthy volunteers following
      the application of electrical stimulation stress. 34 alprazolam-treated patients
      with panic disorder were divided into non-responder and responder group. Vigor
      scores in patients with panic disorder were significantly decreased compared with
      healthy controls. Another score in POMS in patients with panic disorder were
      significantly increased compared with healthy controls. Trait and state anxiety
      of STAI in panic disorder patients were higher than healthy controls. There was
      no difference in either HRV or threshold of electrical stimulation applied
      between panic disorder patients and healthy controls. SAA levels in the responder
      group were significantly elevated compared with the non-responder group and
      controls both before and after electrical stimulation. In addition, there were no
      differences in salivary cortisol levels between responder and non-responder
      groups of patients with panic disorder and control. The sample may not be
      representative of the general population. These preliminary results suggest that
      sAA might be useful predictive biological markers of treatment responsiveness in
      patients with panic disorder.

PMID- 22391147
TI  - Co-development of a companion diagnostic for targeted cancer therapy.
AB  - Oncology drug development is a long and costly process associated with a success
      rate of 5-10%. The parallel development of companion diagnostic tests that will
      identify patients most likely to receive benefit has the potential to increase
      the success rate for oncology drugs and decrease development time and associated
      costs. Metastatic melanoma is a challenging disease that has been associated with
      poor survival. Identification of a mutated BRAF kinase gene in many cases of
      melanoma provided a promising therapeutic target. Here we describe the successful
      co-development of vemurafenib, a first-in-class selective inhibitor of oncogenic
      BRAF kinase, and its companion diagnostic, the cobas((r)) 4800 BRAF V600 Mutation
      Test. Key success factors in the development process included early
      identification of the BRAF V600E biomarker, early development of the diagnostic
      test, and early and close collaboration between the pharmaceutical and diagnostic
      development teams. This focused and integrated process resulted in the first
      personalized medicine for the treatment of metastatic melanoma less than five
      years after the Investigational New Drug Application, a remarkably short time.

PMID- 22391148
TI  - The effect of stochastic fluctuation in radiation dose-rate on cell survival
      following fractionated radiation therapy.
AB  - In radiobiological models, it is often assumed that the radiation dose rate
      remains constant during the course of radiation delivery. However, instantaneous
      radiation dose rate undergoes random (stochastic) temporal fluctuation. The
      effect of stochastic dose rate in fractionated radiation therapy is unknown and
      there has been no analytical formulation of stochastic dose-rate fluctuation
      effect in fractionated radiation therapy which we endeavor to pursue here. We
      have obtained the quantitative expression of cellular survival fraction
      considering stochastic temporal fluctuation or noise in dose rate. We have shown
      that the constant dose-rate approximation overestimates the survival fraction
      compared to that under stochastic dose rate in a fractionated radiation therapy
      situation and this overestimation effect increases appreciably with the increase
      in the fluctuation level in dose rate. However, for a given level of fluctuation
      in dose rate, overestimation of survival fraction also depends on the value of
      cellular radiation sensitivity parameter beta and the repair rate of DNA lesion.
      This overestimation effect is higher for the cells which have a higher value of
      beta parameter or have a lower repair rate. Our study draws attention to
      stochastic temporal fluctuation in the radiation dose rate and its potential
      contribution to cell survival following fractionated radiotherapy.

PMID- 22391149
TI  - The distracted nurse.

PMID- 22391150
TI  - The use of simulation for pediatric oncology nursing safety principles: ensuring
      competent practice through the use of a mnemonic, chemotherapy road maps and case
      based learning.

PMID- 22391151
TI  - Functional and morphological analysis of the subretinal injection of retinal
      pigment epithelium cells.
AB  - Replacement of retinal pigment epithelium (RPE) cells by transplantation is a
      potential treatment for some retinal degenerations. Here, we used a combination
      of invasive and noninvasive methods to characterize the structural and functional
      consequences of subretinal injection of RPE cells. Pigmented cells from primary
      cultures were injected into albino mice. Recovery was monitored over 8 weeks by
      fundus imaging, spectral domain optical coherence tomography (sdOCT), histology,
      and electroretinography (ERG). sdOCT showed that retinal reattachment was nearly
      complete by 1 week. ERG response amplitudes were reduced after injection, with
      cone-mediated function then recovering better than rod function. Photoreceptor
      cell loss was evident by sdOCT and histology, near the site of injection, and is
      likely to have been the main cause of incomplete recovery. With microscopy,
      injected cells were identified by the presence of apical melanosomes. They either
      established contact with Bruch's membrane, and thus became part of the RPE
      monolayer, or were located on the apical surface of the host's cells, resulting
      in apposition of the basal surface of the injected cell with the apical surface
      of the host cell and the formation of a series of desmosomal junctions. RPE cell
      density was not increased, indicating that the incorporation of an injected cell
      into the RPE monolayer was concomitant with the loss of a host cell. The
      transplanted and remaining host cells contained large vacuoles of ingested debris
      as well as lipofuscin-like granules, suggesting that they had scavenged the
      excess injected and host cells, and were stressed by the high digestive load.
      Therefore, although significant functional and structural recovery was observed,
      the consequences of this digestive stress may be a concern for longer-term
      health, especially where RPE cell transplantation is used to treat diseases that
      include lipofuscin accumulation as part of their pathology.

PMID- 22391152
TI  - Immunodominance: a pivotal principle in host response to viral infections.
AB  - We encounter pathogens on a daily basis and our immune system has evolved to
      mount an immune response following an infection. An interesting phenomenon that
      has evolved in response to clearing bacterial and viral infections is called
      immunodominance. Immunodominance refers to the phenomenon that, despite co
      expression of multiple major histocompatibility complex class I alleles by host
      cells and the potential generation of hundreds of distinct antigenic peptides for
      recognition following an infection, a large portion of the anti-viral cytotoxic T
      lymphocyte population targets only some peptide/MHC class I complexes. Here we
      review the main factors contributing to immunodominance in relation to influenza
      A and HIV infection. Of special interest are the factors contributing to
      immunodominance in humans and rodents following influenza A infection. By
      critically reviewing these findings, we hope to improve understanding of the
      challenges facing the discovery of new factors enabling better anti-viral vaccine
      strategies in the future.

PMID- 22391154
TI  - [Expression of HtrA2 and WT1 genes in acute myeloid leukemia].
AB  - Objective of this study was to detect the expression of HtrA2 and WT1 mRNA in
      acute myeloid leukemia (AML) and investigate the relationship of their expression
      levels with clinical variates and correlation between them. The expression levels
      of HtrA2 and WT1 were measured by RQ-PCR in bone marrow cells in 104 newly
      diagnosed AML patients and leukemia cell lines (K562, HL-60, NB4, Kasumi-1,
      U937), and the relationship between expression level and clinical parameters
      (age, sex, WBC count, diagnosis and prognosis) was investigated. The results
      showed that (1) the expression of HtrA2 gene in newly diagnosed AML was lower
      than that of the normal controls (P < 0.01), while expression of WT1 gene in
      newly diagnosed AML was higher than that of the normal controls (P < 0.01), the
      expression levels of HtrA2 and WT1 genes both did not correlate with age, sex and
      WBC counts of patients. There were no significant difference of HtrA2 gene
      expression between different NCCN prognosis group, while WT1 gene expression in
      better-risk group was significantly lower than that in intermediate-risk group (P
      = 0.003). The HtrA2 expression level rose after treatment in both CR group and
      non-CR group (P < 0.05), while WT1 expression level significantly decreased after
      treatment only in CR group (P < 0.01). Negative correlation between HtrA2 and WT1
      expression was also observed (r = -0.249, P = 0.011). It is concluded that the
      low expression of HtrA2 and high expression of WT1 are closely related with
      occurrence and development of acute leukemia, so up-regulating expression of
      HtrA2 and interfering expression of WT1 may become the targets for leukemia
      therapy in the future.

PMID- 22391153
TI  - Extinction from a rationalist perspective.
AB  - The merging of the computational theory of mind and evolutionary thinking leads
      to a kind of rationalism, in which enduring truths about the world have become
      implicit in the computations that enable the brain to cope with the experienced
      world. The dead reckoning computation, for example, is implemented within the
      brains of animals as one of the mechanisms that enables them to learn where they
      are (Gallistel, 1990, 1995). It integrates a velocity signal with respect to a
      time signal. Thus, the manner in which position and velocity relate to one
      another in the world is reflected in the manner in which signals representing
      those variables are processed in the brain. I use principles of information
      theory and Bayesian inference to derive from other simple principles explanations
      for: (1) the failure of partial reinforcement to increase reinforcements to
      acquisition; (2) the partial reinforcement extinction effect; (3) spontaneous
      recovery; (4) renewal; (5) reinstatement; (6) resurgence (aka facilitated
      reacquisition). Like the principle underlying dead-reckoning, these principles
      are grounded in analytic considerations. They are the kind of enduring truths
      about the world that are likely to have shaped the brain's computations.

PMID- 22391155
TI  - [Expression of Kindlins and angiopoietins in acute myeloid leukemia].
AB  - This study was purposed to explore the expression of Ang-1, Ang-2, Tie-2, Kindlin
      2, Kindlin-3 in different leukemia cell lines and bone marrow of acute myeloid
      leukemia (AML) patients and its clinical significance. The levels of Ang-1, Ang
      2, Tie-2, Kindlin-2, Kindlin-3 in bone marrow of AML patients and nontumorous
      control group as well as leukemia cell lines (K562, KG-1a, U937, HL-60 and
      Jurkat) were detected by RQ-PCR. The difference of positive rate and expression
      level between AML patients and controls was analyzed. The relation between 5
      genes and their relationship with typing and prognosis of AML were investigated.
      The results showed that Ang-1, Ang-2, Kindlin-3 expressed in K562, KG-1a, U937,
      HL-60 and Jurkat cells. Tie-2 only expressed in KG-1a and HL-60 cells. Kindlin-2
      expressed in K562, KG-1a and HL-60 cells. All of these 5 genes expressed in AML
      patients and nontumorous controls. The expression level of Ang-1 and Ang-2 in
      patients with higher WBC count (>= 30 * 10(9)/L) was significantly higher than
      that in patients with lower WBC (< 30 * 10(9)/L, P < 0.001, P < 0.001). The
      expression level of Ang-1 and Ang-2 in patients with t(8;21) or t(15;17) was
      significantly lower (P < 0.001, P = 0.005). In the NCCN better-risk group, Ang-1
      expressed lower (P = 0.020). The group with lower expression of Ang-1 showed a
      higher complete remission (CR) rate (P = 0.027). The expression level of Kindlin
      2 was lower in AML patients (P = 0.010), lower in patients with higher WBC (>= 30
      * 10(9)/L, P = 0.020), and higher in patients with t(8;21) or t(15;17). The
      expression levels of both Kindlin-2 and Kindlin-3 were significantly higher after
      CR (P < 0.001, P = 0.004). It is concluded that Ang-1 closely correlated with the
      poor prognosis of AML. Kindlin-2 lowly expresses in AML, which has a close
      relation with the favorable prognosis of AML. Kindlin-2 can be a marker for
      favorable prognosis of AML.

PMID- 22391156
TI  - [Mutational detection of full-length mixed lineage leukemia gene in patients with
      de novo AML-M4 and M5].
AB  - Abnormalities of chromosome 11 involving mixed lineage leukemia (MLL) on 11q23
      are often seen in acute myeloid leukemia (AML)-M5 or AML-M4. The fusion gene of
      MLL-PTD and MLL plays a critical role in the pathogenesis of these AML. However,
      rare chromosome abnormalities have been identified in this type of leukemia. To
      explore whether there were other MLL gene mutations at M4 and M5, in this study
      all of the MLL exons were sequenced at cDNA level. 25 patients with de novo AML
      M4 or M5 with normal karyotypes excluding M4eo and MLL fusion gene or MLL-PTD
      were selected, the amplification and direct sequencing analysis of full length
      MLL gene exons were carried out, then the mutations found were verified at
      genomic DNA level. Furthermore, the point mutations were tested in normal samples
      and a larger group of AML patients using the platform of Mass Array. The results
      showed that high-frequency deletion/insertion and point mutations in RD, PHD, TAD
      and SET domains of MLL were found, while these alterations in normal samples and
      other subtypes of AML samples were also verified, and without significant
      difference (P > 0.05). It is concluded that a variety of deletions/insertions in
      MLL mRNA and point mutations are respectively alternative splicing of MLL gene at
      transcriptional level and single nucleotide polymorphism. These alternations
      together constituted genetic polymorphisms of MLL. Although these variations may
      not play a direct role in the molecular pathogenesis of AML-M4 or M5, their
      correlations to clinical treatment and prognosis need to be further explored.

PMID- 22391157
TI  - [Regulatory mechanisms of PI3K/AKT signaling pathway in acute leukemia].
AB  - This study was aimed to analyze the expression profiles of PI3K/AKT signaling
      pathway genes from bone marrow samples of AML and ALL patients and normal
      samples. AML, ALL and normal bone marrow samples were collected from 6 AML, 6 ALL
      patients and 4 normal persons. The expression of PI3K/AKT signaling pathway genes
      including PTEN, CCND1, mTOR, RICTOR, FOXO1 were detected by real-time fluorescent
      quantification RT-PCR while GAPDH gene expression was used as an internal
      reference. The relative gene expression level was calculated by the method of the
      2(-DeltaDeltaCt). The results showed that the gene expression profiles were
      different between normal and leukemic groups. PTEN, mTOR and RICTOR expression
      levels were down-regulated, while FOXO1 and CCND1 levels were up-regulated in AML
      and ALL. PTEN was down-regulated in 10 out of the 12 samples; mTOR was down
      regulated in 9 out of the 12 samples; RICTOR was down-regulated in 7 out of the
      12 samples; FOXO1 was up-regulated in 9 out of the 12 samples and CCND1 was up
      regulated in 7 out of the 12 samples. It is concluded that PI3K/AKT signal
      pathway is activated in both AML and ALL leukemic cells.

PMID- 22391158
TI  - [Analysis of PTPN11 mutation in children leukemia and its clinical significance].
AB  - This study was aimed to explore the frequency of PTPN11 mutation in children with
      leukemia and its clinical significance. Genomic DNAs were extracted from
      peripheral leukocytes of 131 patients with leukemia, including 101 cases of ALL,
      26 cases of AML, 3 cases of CML and 1 case of juvenil myelomonocytic leukemia
      (JMML). The sequences of PTPN11 exons 3, 8, 13 were amplified by polymerase chain
      reaction (PCR), and the clinical characteristics of positive patients were
      analyzed. The results indicated that the PTPN11 mutation was found in 10 cases
      (9.9%) from newly diagnosed 101 cases of ALL. Grouping the newly diagnosed ALL
      children by various clinical features, it was found that the PTPN11 mutation did
      not show associations with sex, age, white blood cell (WBC) count, prednisone
      test sensitivity, clinical risk and disease recurrences at the first visit (P >
      0.05). PTPN11 mutations were found in 2 cases out of 26 AML patients, including
      one AML-M(2) and one AML-M(4). No PTPN11 mutation in 3 CML patients was found.
      Exon 13 mutation of PTPN11 gene was found in 1 case of JMML. It is concluded that
      the E76 of exon 3 is the hot spot of PTPN11 mutation in children leukemia. The
      novel G503E (1508G > A) mutation is detected in one JMML patient. The PTPN11
      mutation does not associate with the sex, age, WBC count, prednisone sensitive
      test and early recurrence.

PMID- 22391159
TI  - [Immunogenetic diagnosis of large granular lymphocytic leukemia and therapy by
      sirolimus].
AB  - This study was aimed to investigate the immunogenetic diagnosis of large granular
      lymphocytic leukemia (LGLL) and therapeutic efficacy of sirolimus, and to
      analysis 256 cases of LGLL reported at home and abroad within 2000 - 2010.
      Besides the routine examination of peripheral blood and classification of bone
      marrow cell morphology, the expression of T cell receptor variable region of beta
      chain (TCR BV), CD3, CD4 and CD8, as well as TCRalphabeta, TCRgammadelta were
      detected by flow cytometry; the RT-PCR was used to amplify and determine the TCR
      gene spectrotypes, and to analyze the clonality of abnormal cells. Sirolimus was
      first given to patients who did not gain efficacy from common agents. The results
      showed that lymphocytosis happened in all LGLL patients, but patients from West
      countries always displayed neutropenia while Chinese patients always displayed
      anemia. In 2 out of 4 patients from our hospital, the large granular lymphocytes
      (LGL) were difficult to be distinguished. In all 4 patients, almost all
      lymphocytes were CD3(+), CD8(+), and TCRalpha/beta(+). TCR BV 24 gene family
      clones showed monoclonal TRBV 23, TRBV 20, TRBV 13.6, and TRBV 13.6,
      respectively. FCM results were consistent with those of RT-PCR. When 4 patients
      had been given sirolimus (6 mg first dose, 2 mg once a day) for about 1 week,
      hemoglobin level and reticulocyte count increased significantly without any
      serious side effects. It is concluded that the detection of specific lymphocyte
      monoclonal TCR BV 24 gene family by FCM contributes to the diagnosis of LGLL.
      Sirolimus is an effective agent without serious side effect for LGLL patients,
      especially for patients who cannot tolerate common drugs.

PMID- 22391160
TI  - [Regulation of all-trans retinoic acid and arsenic trioxide on CD44v6 expression
      in NB4 cells].
AB  - The adhesion molecule CD44 variant isoform (CD44v6) closely associates with
      progress of acute myeloid leukemia (AML). This study was purposed to investigate
      the effects of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) on the
      expression of CD44v6 and the associated signal pathway phosphatidylinositol 3
      kinase (PI3K)/Akt in acute promyelocytic leukemia (APL) cell line NB4 cells. The
      differentiation of NB4 was detected by morphologic observation and flow
      cytometry; the NB4 cell apoptosis was assayed by flow cytometry with Annexin V
      FITC/PI double staining; the CD44v6 mRNA expression in NB4 cells was determined
      by real-time RT-PCR, the CD44v6 protein expression and changes of PI3K/Akt signal
      pathway in NB4 cells were analysed by Western blot. The results demonstrated that
      in ATRA-induced differentiation, the transcriptional level of CD44v6 was
      dominantly down-regulated, the translational level of CD44v6 did not change and
      the PI3K/Akt signal axis was activated. In As2O3-induced apoptosis, both the
      transcriptional level and translational level of CD44v6 were remarkably reduced,
      and the PI3K/Akt pathway was inhibited. It is concluded that the regulation of
      ATRA on expression of CD44v6 in NB4 cells differs from that of As2O3. The results
      provide an experimental basis to reveal the different mechanism of ATRA and As2O3
      in view of the intercommunication between leukemia cells and hematopoietic
      microenvironment.

PMID- 22391161
TI  - [Clinical diagnostic significance of cerebrospinal fluid detection with flow
      cytometry in children acute lymphoblastic leukemia accompanied by central nervous
      system leukemia].
AB  - This study was aimed to explore the clinical diagnostic significance of
      cerebrospinal fluid detection with flow cytometry (FCM) in children acute
      lymphoblastic leukemia (ALL) accompanied by central nervous system leukemia
      (CNSL). The 75 cerebrospinal fluid (CSF) samples of children with de novo ALL
      were detected by FCM, conventional cytology (CC), CSF routine tests and
      cytochemical examination. The results showed that among 75 de novo ALL, median
      age of onset was 5 (1 - 14) years old, ratio of male/female was 1.3:1. According
      to CCLG2008-ALL risk group protocol, there were 38 cases of standard risk
      (50.7%), 22 cases of intermedia risk (29.3%), 15 cases of high risk (20%). The
      results of CSF detection showed FCM(+)CC(+) 5 cases (6.7%), FCM(+)CC(-) 8 cases
      (10.7%) and FCM(-)CC(-) 62 cases (82.7%). According to CNS status classified,
      there were 3 cases of CNS-2, 2 cases of CNS-3 in FCM(+)CC(+) group there were CNS
      1 7 cases, CNS-2 1 case in FCM(+)CC(-) groups, there were CNS-1 60 cases, CNS-2 1
      case, CNS-3 1 case in FMC(-)CC(-) group. There was no significant difference in
      the distribution of the CNS-1, -2, -3 among the FCM(+)CC(+), FCM(+)CC(-), FCM(
      )CC(-) groups (P > 0.05). It may be related to the fewer samples. There was
      higher consistency between results of FCM and CC on CNS-2, -3 diagnoses. FCM
      increased CC diagnosis positive rate to 20%. Meanwhile, there was no malignant
      cell in the smear, and no abnormal lymphocytic immunophenotype could be seen in
      CSF samples from 9 cases of viral encephalitis. It is concluded that
      cerebrospinal fluid detection with FCM has higher sensitivity, which is an
      important supplement to CSF routine detections and has significant useful value
      in diagnosis of children CNSL.

PMID- 22391162
TI  - [Effects of interferon-alpha combined with homoharringtonine on K562 cell
      proliferation and beta-catenin expression].
AB  - The study was aimed to investigate the synergistically effect of interferon-alpha
      (IFN-alpha) and homoharringtonine (HHT) on the proliferation, apoptosis, cell
      cycle of K562 cells and the expression of beta-catenin. The proliferation,
      apoptosis, cell cycle and beta-catenin mRNA expression of K562 cells treated with
      IFN-alpha and/or HHT were assayed with MTT, flow cytometry or RT-PCR
      respectively. The results showed that HHT alone, but not IFN-alpha alone,
      displayed a proliferation inhibition, apoptosis induction, G(0)/G(1) phase block
      and down-regulation of beta-catenin expression in K562 cells with concentration-
      and time-dependent manners. The expression level of beta-catenin mRNA after being
      treated with HHT was 0.5576 +/- 0.0373, which were lower than that in control
      group (0.9369 +/- 0.0142). The down-regulation of beta-catenin expression in
      group of IFN-alpha combined with HHT was higher significantly than that in HHT
      group (0.3737 +/- 0.0529 vs 0.5576 +/- 0.0373, P < 0.05). Otherwise, HHT combined
      with IFN-alpha did not demonstrate obvious toxicologic effect on bone marrow
      mononuclear cells. It is concluded that IFN-alpha combined with HHT can enhance
      the cytotoxic effect of HHT on K562 cells, which may be associated with down
      regulation of beta-catenin expression.

PMID- 22391163
TI  - [Decitabine inhibits cell proliferation and induces apoptosis of all-trans
      retinoid acid-resistant acute promyelocytic leukemia NB4-R2 cell line].
AB  - The aim of this study was to investigate the proliferation-inhibitory and
      inducing apoptotic effects of decitabine (DAC) on acute promyelocytic leukemia
      NB4-R2 cells. Cell inhibitory rate was determined by cell proliferation and
      cytotoxicity assay (WST-1 assay) after NB4-R2 cells were treated with 0.01 - 0.5
      umol/L DAC for 24, 48 and 72 h. Apoptosis of NB4-R2 cells treated with 0.05 - 5
      umol/L DAC for 48 h was detected by flow cytometry with PI staining and
      AnnexinV/PI staining. Reverse transcription-PCR (RT-PCR) was used to determine
      the mRNA expression level of MDR1 gene encoding P-glycoprotein (P-gp). The
      results indicated that DAC (0.01 - 0.5 umol/L) inhibited the proliferation of NB4
      R2 cells in both time- and concentration-dependent manners. The IC(50) of DAC on
      the viability of NB4-R2 cells after treatment for 48 and 72 h were 0.089 and
      0.064 umol/L respectively. DAC (0.05 - 5 umol/L) induced NB4-R2 cell apoptosis in
      dose-dependent manner with down-regulation of MDR 1 gene expression. It is
      concluded that a low concentration of DAC (< 0.5 umol/L) inhibits cell
      proliferation, while higher concentration of DAC (1 or 5 umol/L) induces
      apoptosis on NB4-R2 cells, accompanied with reduction of MDR1 levels.

PMID- 22391164
TI  - [Dynamic monitoring of plasma circulating DNA in patients with acute myeloid
      leukemia and its clinical significance].
AB  - This study was aimed to quantify plasma circulating DNA level in patients with
      acute myeloid leukemia (AML) and to evaluate its clinical significance. 66 AML
      patients and 100 controls (60 healthy subjects for health examination, 20 cases
      of benign hematopathy, and 20 cases of solid tumors) were enrolled in this study.
      Blood samples were collected from AML patients at different status of disease and
      control groups. Circulating DNA were drew by using the BILATEST DNA Kit. The
      level of plasma DNA was determined by using duplex real-time quantitative PCR.
      The results showed that the median value of plasma DNA level in AML patients at
      diagnosis was 168.5 (73.4 - 245.1) ng/ml, significantly higher than those in
      three control groups, and the median level in male patients was significantly
      higher than that in female patients (P = 0.019). No significant difference was
      found in plasma DNA level of the patients at different ages and with different
      FAB subtypes. Compared with level before chemotherapy, the plasma DNA levels in
      complete remission patients and partial remission patients decreased
      significantly, and with no statistical difference from level of healthy controls,
      but was significantly different from level of non-remission patients (P < 0.05).
      Following up of 31 remission patients showed that the plasma DNA level increased
      in 5 out of 6 (83.3%) relapsed patients, but no increase was found in 22 out of
      25 (88.0%) non-relapsed patients. It is concluded that the quantification of
      plasma DNA may be useful for evaluating therapeutic effects and monitoring
      relapse in AML patients.

PMID- 22391165
TI  - [Influence of crocin on proliferation in vitro and function of dendritic cells
      derived from bone marrow of children with acute leukemia].
AB  - This study was purposed to investigate the effect of crocin on the proliferation
      in vitro and immune function of dendritic cells (DC) derived from the bone marrow
      of children with acute leukemia. The mononuclear cells were isolated from bone
      marrow of leukemia children by Ficoll-Hypaque. The experiment was divided into
      six groups: blank control group (A), crocin 1.25 mg/ml group (B), cytokines (rhGM
      CSF 75 ng/ml+rhIL-4 75 ng/ml+rhTNF-alpha 50 ng/ml) group (C), cytokines+crocin
      0.3125, 1.25 or 5.0 mg/ml groups (D, E, F). The numbers of DC were counted and
      the phenotypes of DC were determined by flow cytometry on the ninth day of
      culture. The DC of different groups were mixed with T cells just separated from
      peripheral blood of another children with acute lymphoblastic leukemia, and
      cultured with rhIL-2 200 U/ml for 5 d. The function of DC was detected by mixed
      lymphocyte reaction (MLR). The results indicated that the test groups and control
      group all obtained a certain amount of typical DC, but the DC numbers in test
      groups were all higher than those in control group (P < 0.01). Cultured for 9
      days, the rates of CD1a(+), CD83(+), and HLA-DR(+) in group C, D, E, F were
      higher than group A (P < 0.01). There was no statistically significant difference
      between A and B groups (P > 0.05). MLR showed that with the increasing of DC, the
      stimulation index of T cells in group A and B was not rising (P > 0.05); the
      stimulated index of T cells in group C and E was significantly rising, there was
      statistically significant difference between them (P < 0.01). When the number of
      stimulated cells was the same, the stimulation index of T cell in group E was the
      highest (P < 0.01). It is concluded that the capability of DC proliferation
      promoted by crocin alone is lower than that of its combination with rhGM-CSF,
      rhIL-4 and rhTNF-alpha, but the crocin can synergically promote the maturity of
      DC cooperating with rhGM-CSF, rhIL-4 and rhTNF-alpha. The DC induced by crocin
      can particularly enhance the proliferation of T cells.

PMID- 22391166
TI  - [Influence of mesenchymal stem cells on proliferation of HL-60].
AB  - The objective of this study was to explore the effect of mesenchymal stem cells
      (MSC) on HL-60 proliferation and its molecular mechanism. HL-60 cells co
      cultivated with MSC were used as experiment group, and the cells cultivated
      solely were taken as control group. HL-60 cells in the two groups were counted at
      different time. The time-quantity curve was drawn. The cell cycle and apoptosis
      ratio of HL-60 cells were compared between the two groups and expressions of
      Survivin and Bcl-2 protein were detected by flow cytometry. The results showed
      that HL-60 cells cultivated with MSC were obviously inhibited, especially on day
      5 and 7 (P < 0.01). HL-60 cells were distributed on the phase of G(0)/G(1)
      [control group (47.0 +/- 9.0)% vs experiment group (70.0 +/- 16.0)%, P = 0.003],
      and apoptotic peak appeared. Both of Survivin and Bcl-2 protein expressions in HL
      60 cells decreased [Bcl-2 protein in control group (63.0 +/- 9.1)% vs experiment
      group (50.0 +/- 14.1)%, P = 0.045; Survivin in control group (94.0 +/- 9.3)% vs
      experiment group (77.0 +/- 11.8)%, P = 0.006]. It is concluded that the MSC can
      inhibit HL-60 cell proliferation, and promote HL-60 cell apoptosis.

PMID- 22391167
TI  - [Effect of triptolide on sensitivity of K562/A02 cell line to adriamycin].
AB  - This study was aimed to evaluate the effect of triptolide (TPL) on the reversal
      of multidrug resistance in K562/A02 cell line. The sensitivity of K562 and
      K562/A02 to adriamycin (ADM) and reversal of drug resistance were determined with
      MTT method. The concentration of intracellular ADM and P-glycoprotein expression
      were detected by flow cytometry. Luciferase reporter gene assay was used to
      detect the transcriptional activity of MDR1 promoter. The results showed that TPL
      significantly decreased the resistance degree of K562/A02 cells, inhibited P
      glycoprotein expression (mean fluorescent intensity decreased from 123 +/- 13 to
      39 +/- 13) and increased the intracellular concentration of ADM (mean fluorescent
      intensity increased from 18 +/- 5 to 34 +/- 6) in K562/A02 cells. Luciferase
      reporter gene assay demonstrated that TPL inhibited the transcriptional activity
      of MDR1 promoter by 75%. It is concluded that TPL may effectively reverse the
      multidrug resistance in K562/A02 cells via modulating P-glycoprotein expression
      and increasing intracellular ADM accumulation.

PMID- 22391168
TI  - [Clinical study on efficiency of fludarabine-based regimen for the patients with
      chronic lymphocytic leukemia].
AB  - The aim of this study was to evaluate the therapeutic effects and adverse
      reactions of fludarabine-based regimen for patients with chronic lymphocytic
      leukemia(CLL).18 patients with CLL were treated with F regimen [fludarabine 30
      mg/(m(2).d) intravenously for 3 d, repeatedly every 28 days]. 22 patients were
      treated with FC regimen [fludarabine 25 mg/(m(2).d) plus cyclophosphamide 250
      mg/(m(2).d) intravenously for 3 d, repeatedly every 28 days]. The results showed
      that the rate of complete remission (CR), partial remission (PR) and overall
      remission (OR) reached 16.7%, 61.1% and 77.8% in the F regimen groups and 59.1%,
      40.9% and 100% in the FC regimen groups (P < 0.05, P > 0.05 and P > 0.05),
      respectively. FC regimen resulted in significantly higher CR rate than that in
      single-agent fludarabine regimen. The main adverse reactions were
      myelosuppression and immunosuppression. No significant differences were found
      between the two regimens. FC regimen did not increase the rate of severe
      infections. It is concluded that FC regimen can give higher CR rate as compared
      with F regimen, fludarabine-based regimens is effective and safe first-line
      regimen for patients with CLL.

PMID- 22391169
TI  - [Mitochondria-mediated apoptosis induced by 5-aminolevulinic acid-based
      photodynamic therapy in HL-60 cells].
AB  - This study was purposed to investigate the changes of mitochondrial membrane
      potential (MMP) and apoptosis-related gene Bcl-2 expression of HL-60 cells
      treated with 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT). HL-60
      cell line was used as a model and divided into 4 groups: ALA group, PDT group,
      ALA+PDT group and control group. The change of MMP was detected by flow cytometry
      with JC-1 (lipophilic cation 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethyl
      benzimidazol-carbocyanine iodide); the mRNA expression of Bcl-2 was determined by
      semi-quantitative RT-PCR and real-time PCR. The results demonstrated that MMP
      significantly decreased after treatment with ALA-PDT and the ratio of cells with
      disrupted MMP obviously increased in ALA+PDT group in time-dependence manner, as
      compared with control, ALA and PDT groups (P < 0.05), while no difference between
      ALA and PDT groups was found. The semi-quantitative RT-PCR and real-time PCR
      showed that the expression level of Bcl-2 was obviously down regulated at 2 h
      after ALA-PCT, further down-regulated at 4 h, and lasted in low level at 24 h. It
      is concluded that ALA-PDT-induced apoptosis of HL-60 cells is associated with its
      effect on MMP, that is ALA-PDT promotes cell apoptosis through effect on
      mitochondrial function.

PMID- 22391170
TI  - [RQ-PCR detection of GST-pi and LRP genes in adult acute leukemia and its
      clinical significance].
AB  - This study was aimed to detect the glutathione S-transferase-pi (GST-pi) and lung
      resistance-related protein (LRP) genes and to investigate their relationship with
      multidrug resistance (MDR) of patients with acute leukemia (AL). Real-time
      fluorescent quantitative reverse transcription polymerase chain reaction (RQ-PCR)
      was used to detect the expression of GST-pi and LRP genes in peripheral blood
      mononuclear cells from 44 AL patients and 27 normal subjects. The results showed
      that the significant difference in GST-pi expression level was found between
      newly diagnosed patients and complete remission patients and between refractory
      patients and complete remission patients (P < 0.01), while expression level of
      LRP genes showed obvious difference (P <= 0.01) between newly diagnosed patients
      and refractory patients and between complete remission patients and refractory
      patients. Statistical analysis indicated that there was no correlation between
      GST-pi gene and LRP gene. The expression of GST-pi and LRP genes was not
      significantly different in different white blood cell (WBC) count groups and
      different clinical typing groups (ALL and ANLL). It is concluded that the
      mechanism of MDR resulting from GST-pi and LRP genes is different, thereby
      combination detection of GST-pi and LRP genes demonstrates a larger role for
      evaluating prognosis of AL patients, as compared with detection of GST-pi or LRP
      gene alone. The WBC count and leukemia typing have no relationship with
      expression of GST-pi and LRP genes.

PMID- 22391171
TI  - [Expression of Notch signal molecules in human lymphoma cells and its
      significance].
AB  - The study was aimed to investigate the expression of Notch signal molecules in
      human lymphoma cells and its significance. Raji, Maver, Z138 and Jurkat cell
      lines were used in the study. RT-PCR was used to determine the expression of
      Notch signaling molecules in these lymphoma cells. Flow cytometry was used to
      detect the apoptosis and cell-cycle of the lymphoma cells induced by different
      concentrations of gamma secretase inhibitor DAPT. CCK-8 was used to detect the
      proliferation of the lymphoma cells treated by DAPT. The results showed that the
      expression of Notch molecules in the four cell lines was different. Notch1 and
      Notch2 were found to be expressed in the four lymphoma cell lines, Notch3
      predominantly expressed in Jurkat cells, Notch4 only expressed in Raji cells
      weakly and Hes1 only expressed in Raji and Jurkat cells. Treatment with DAPT
      could increase the apoptosis ratio of Raji and Jurkat cells. Besides, DAPT could
      significantly inhibit the proliferation of Raji and Jurkat cells by inducing the
      cell cycle arrest in G(1) phase, but the effect of DAPT on Maver and Z138 cells
      was not obvious. The activity of Notch pathway could be inhibited by DAPT
      treatment through down-regulating the expression of Notch target gene Hes1. It is
      concluded that the abnormal expression and activation of Notch signal pathway
      play an important role in the proliferation of lymphoma cells. Notch may be
      likely a new target for the therapy of lymphoma.

PMID- 22391172
TI  - [Silencing of survivin gene in Jeko-1 cell line with small interfering RNA].
AB  - This study was aimed to investigate the impact of specific siRNA on survivin gene
      in transfected lymphoma cell line and provide experimental evidences for future
      treatment of mantle cell lymphoma. The small interfering RNA (siRNA) targeted
      survivin mRNA was synthesized in vitro and was transfected into Jeko-1 that
      showed high survivin expression in mRNA level. The levels of survivin mRNA and
      protein expression were detected by quantitative reverse transcription polymerase
      chain reaction (RT-PCR) and Western blot respectively. The apoptosis effect was
      examined by calculating the ratio of Annexin V-FITC/PI positive cells using flow
      cytometry. The inhibition of cell proliferation was assayed with CCK-8 reagent
      after transfection. The results showed that expression of survivin mRNA was
      markedly suppressed by the siRNA. The relative expression levels were 0.49 +/-
      0.03, 0.38 +/- 0.02 and 0.17 +/- 0.02 at time points of 24, 48 and 72 h
      respectively, compared with the control group; the inhibitive rates of cell
      proliferation were (31.2 +/- 2.1)%, (43.3 +/- 3.4)% and (52.6 +/- 2.5)%; the
      apoptotic rates of cells were (6.3 +/- 0.5)%, (13.5 +/- 1.1)% and (23.6 +/- 1.6)%
      respectively; survivin protein expression levels were gradually reduced. It is
      concluded that the siRNA targeting survivin down-regulates the expressions of
      survivin mRNA and protein evidently. The siRNA of survivin displays the potent
      ability to inhibit the proliferation of lymphoma cell line Jeko-1; survivin may
      become a potential molecular target for the therapy of lymphoma in the future.

PMID- 22391173
TI  - [Characteristics of two cases of Burkitt lymphoma/leukemia with concurrent
      t(8;14) and t(14;18)].
AB  - This article aimed to report two cases of Burkitt lymphoma/leukemia with
      concurrent t(8;14) and t(14;18). Morphology, immunophenotype, cytogenetics and
      molecular biology (MICM) methods were applied to diagnosis. The results showed
      that the two cases were both acute lymphocytic leukemia L3 type according to FAB
      criteria. Conventional cytogenetic technique or interphase fluorescence in situ
      hybridization (FISH) demonstrated that t(8;14) and t(14;18) were detected
      concurrently in both patients. CD20, CD10, FMC7, CD38 and CD19 were expressed in
      both patients by immunophenotyping. According to MICM, they were both diagnosed
      as Burkitt lymphoma/leukemia. The first patient died in one month after
      chemotherapy, and the second patient survived 19 months after rituximab- combined
      high-dose chemotherapy and subsequently allogeneic hematopoietic stem cell
      transplantation (HSCT). In conclusion, t(8;14) and t(14;18) may present
      simultaneously in Burkitt lymphoma/leukemia and indicate poor prognosis.
      Rituximab-combined chemotherapy and subsequently HSCT could improve the outcomes
      of such cases.

PMID- 22391174
TI  - Incipient Coombs' test negative autoimmune hemolytic anemia precedes non
      Hodgkin's lymphoma.
AB  - The cases of lymphoma accompanied or preceded by Coombs' test positive autoimmune
      hemolytic anemia (AIHA) have been reported. However, Coombs' test negative AIHA
      prior to the diagnosis of lymphoma was rarely described. Herein, this article
      reports a case of non-Hodgkin's lymphoma (NHL) preceded about 1.5 years by Coombs
      test negative AIHA. A woman aged 69 was diagnosed with HA based on the history
      and laboratory tests. Further studies revealed that this patient was negative
      with Coombs' test for IgG, IgM, IgA and C3. After all possible causes of HA,
      especially malignancies were ruled out, the patient was diagnosed with Coombs'
      test negative AIHA and treated with prednisolone. The patient responded well
      initially to steroid treatment. Two recurrences of acute HA were presented at
      time of 10 months post steroid cessation, and immediately after an attempt to
      withdraw steroid, respectively, but the hemolysis was effectively controlled by
      reinstitution of prednisolone. At third recurrence, however, the patient was no
      longer responding to steroid, and was found with cervical lymphadenopathy.
      Coombs' test for IgG, IgM, IgA and C3 remained negative. B cell NHL was diagnosed
      by pathology. After receiving 6 cycles of CHOP chemotherapy, the patient was
      lymphoma free, but the hemolysis was not improved, however, which was effectively
      controlled by the following low dose-rituximab (RTX) therapy. The patient was
      still kept in a remission of lymphoma free of anemia. In conclusion, this report
      presented a very rare case of NHL with Coombs' test negative AIHA as initial
      major clinical manifestation.

PMID- 22391175
TI  - [Prognostic value of P53 aberrations in diffuse large B-cell lymphoma].
AB  - The aim of this study was to analyze the P53 aberrations in diffuse large B-cell
      lymphoma (DLBCL) and its prognostic value. Using fluorescence in situ
      hybridization (FISH), the P53 gene was detected in paraffin-embedded tonsil
      tissues from 50 cases of DLBCL, while all the peripheral blood of patients was
      collected for detecting P53 protein in serum by using enzyme-linked immunosorbent
      assay (ELISA). The relationships between P53 gene and protein expression and the
      prognosis of patients with DLBCL were analyzed. The results showed that 21 out of
      50 cases had P53 gene deletion, serum P53 protein content was (176.25 +/- 61.25)
      pg/ml, which was higher than that in normal controls. The Cox model likelihood
      ratio test found that abnormal P53 could be used as independent prognostic factor
      in DLBCL patients. The risk of death in patients with P53 gene deletion were more
      than that in patients with P53 gene normal. The patients with histology P53 gene
      deletion detected by FISH also had relatively high level of mutant P53 protein in
      serum. It is concluded that P53 aberrations in patients with DLBCL can be used as
      an independent prognostic factor, the early detection of P53 in DLBCL patients
      helps to determine their prognosis accurately.

PMID- 22391176
TI  - [Predicating the sensibility of patients with multiple myeloma to glucocorticoid
      by cochaperone P23].
AB  - This study was aimed to investigate the sensitive index for predicting the
      sensitivity of patients with multiple myeloma (MM) to glucocorticoid (GC). MM1.S,
      MM1.R cell lines and 10 MM patients sensitive or non-sensitive to GC were
      enrolled in this study. The expression of heat shock protein 90 (HSP90) and P23
      in peripheral blood mononuclear cells (PBMNC) of MM patients was detected by
      Western blot, and its relation with GC resistance was explored. The results
      showed that there were no differences in HSP90, GR and IkappaB-alpha expressions
      among MM1.S, MM1.R, PBMNC of normal persons and MM patients, while there was
      apparent difference in P23; along with increasing of dexamethasone dose, the
      survival rate of MM1.S decreased, but that of MM1.R did not change so obviously.
      Among 7 cases with P23 low expression, combination treatment scheme with GC was
      effective in 6 cases (86%), uneffective in 1 cases (14%); while among 3 cases
      with P23 high expression, 1 cases (33%) showed effective to combination treatment
      with GC, 2 cases (67%) showed uneffective (P < 0.05). It is concluded that the
      P23 expression may predict the sensitivity of MM patients to GC and may be used
      as index for guiding clinical treatment.

PMID- 22391177
TI  - [Caspase-independent apoptosis induced by arsenic trioxide in human multiple
      myeloma cell RPMI8226].
AB  - This study was purposed to explore the caspase-independent apoptosis pathway in
      human multiple myeloma cell RPMI8226 induced by arsenic trioxide (As(2)O(3)). MTT
      method was used to analyze the proliferation inhibition rate; flow cytometry was
      used to detect the apoptosis rate; Western blot was used to determine the
      expressions of BCL-2 and Caspase-3 in RPMI8226 cells. The results showed that
      As(2)O(3) (0.1 - 20 umol/L) significantly inhibited the proliferation of RPMI8226
      (P < 0.05) in concentration- and time-dependent manner. Compared with the group
      treated with As(2)O(3) (10 umol/L) alone, the apoptosis rate of zVAD-fmk (20
      umol/L) and As(2)O(3) combined treated group did not change. Compared with the
      group treated with As(2)O(3) (10 umol/L) alone, zVAD-fmk (20 umol/L) combined
      with As(2)O(3) (10 umol/L) treatment group showed significant increase of
      expressions of Caspase-3 and BCL-2. It is concluded that As(2)O(3) can inhibit
      the proliferation of RPMI8226 cells. As(2)O(3) can induce apoptosis of RPMI8226
      cells, and a caspase-independent process probably exist in As2O3-inducing
      RPMI8266 cells apoptosis.

PMID- 22391178
TI  - Effects of arsenic trioxide combined with bortezomib on apoptosis of multiple
      myeloma cell line KM3 and its mechanisms.
AB  - This study was purposed to investigate the effect of bortezomib (Bor) and arsenic
      trioxide (As(2)O(3)) combination on multiple myeloma cell line KM3 and its
      mechanisms. KM3 cells were cultured with different concentration of Bor or
      As(2)O(3) as well as both for a certain time. The cell proliferation was analysed
      by MTT assay and the concentration of 50% proliferation inhibition (IC(50)) was
      calculated. Early apoptosis and late apoptosis of KM3 cells were detected by
      Annexin-V-FITC Kit, and the change of transmembrane potential was measured by
      flow cytometry. mRNA of Caspase-3, Bim and Bcl-xL were detected by RT-PCR. The
      results showed that the proliferation inhibitory rate of KM3 cells treated by Bor
      plus As(2)O(3) was much higher than that of KM3 cells treated by Bor only for 72
      h [ (27.64 +/- 0.81)% vs (21.67 +/- 2.20)%, P < 0.05]. There were more KM3 cells
      treated by Bor plus As(2)O(3) in early apoptosis at 48 h and late apoptosis at 72
      h than that of KM3 cells treated only by Bor [ (53.20 +/- 3.70)% vs (35.40 +/-
      2.58)%, P < 0.01; (63.96 +/- 2.97)% vs (54.08 +/- 3.76)%, P < 0.01].
      Transmembrane potential (Deltapsim) of KM3 cells treated by Bor plus As(2)O(3)
      decreased more at 48 h, as compared with Bor alone. The expression levels of
      caspase-3 mRNA and Bim mRNA in KM3 cells treated with Bor plus As(2)O(3) were
      higher than that in KM3 cells treated with Bor alone. But the expression level of
      Bcl-xL mRNA was lower than that in KM3 cells treated with Bor alone. It is
      concluded that As(2)O(3) can enhance the apoptosis-inducing effect of Bor on
      multiple myeloma cell line KM3, which is associated with decreasing the
      expression of Bcl-xl mRNA and increasing the expression of Caspase-3 and Bim
      mRNA.

PMID- 22391179
TI  - [Correlation of laboratory indexes with prognosis in patients with
      myelodysplastic syndrome].
AB  - The myelodysplastic syndrome (MDS) is a group of hematopoietic stem cell-clonal
      disease. The International Prognostic Scoring System (IPSS) is mainly used for
      its prognostic classification, but still remains some unrepeatable results in the
      same group of patients with MDS. This study was aimed to compare the levels of
      peripheral blood mean corpuscular volume (MCV), serum lactate dehydrogenase
      (LDH), beta2-microglobulin (beta2-MG), ferroprotein (SF), Vit B12 in patients
      with MDS classified by IPSS and to explore the relationship between the prognosis
      and laboratory indexes above mentioned in MDS patients. 116 patients with MDS
      were divided into 4 group: low-risk, intermediate risk-I, intermediate risk-II
      and high-risk according to IPSS. The index of MCV, serum LDH, beta2-MG, SF and
      Vit B12 in MDS patients prior treatment and in normal control group were
      detected. Data with normal group and each groups of MDS were compared. The
      results showed that the levels of MCV, LDH, beta2-MG, SF were Vit B12 in patients
      with MDS were significantly higher than those in normal control group (P < 0.05).
      There were significant differences of serum LDH among the 4 groups of MDS (P <
      0.05), and the levels of serum LDH increased in turn: low-risk, intermediate risk
      I, intermediate risk II and high-risk. Serum beta2-MG level in the high-risk
      group was significantly higher than that in the groups of low risk, intermediate
      risk I and intermediate risk II (P < 0.05), the difference among the latter three
      groups was not statistically significant (P > 0.05). There were no significant
      differences in MCV, SF and Vit B12 levels of all groups compared with each other.
      It is concluded that the level of serum LDH and beta2-MG seems to have a certain
      correlation with the progress and prognosis of the MDS, which may be useful for
      predicting the prognosis of the MDS besides IPSS scoring system.

PMID- 22391180
TI  - [Relationship between polymorphism of HLA-A, -B, -DRB1 alleles and susceptibility
      of children to acquired aplastic anemia].
AB  - The aim of this study was to identify the relationship between susceptibility of
      children to acquired aplastic anemia (AA) and HLA-A, -B, -DRB1 alleles. 80
      children with AA were enrolled in this study. Among of them, 34 patients
      collected from tissue typing test centers of Nanfang Hospital; 46 patients were
      diagnosed at Department of Pediatrics of Sun Yat-Sen Memorial Hospital. In these
      patients, 48 were males, 32 were females, and with average age 8.1 years old, 6
      cases were non-severe AA (nSAA), 74 case were severe AA (SAA). The healthy
      control group consisted of 109 donors who were from the same area. All the
      patients and healthy controls were of Han Chinese, and all were unrelated
      individuals. The polymerase chain reaction sequence specific primers (PCR-SSP)
      was used to analyze the polymorphism of HLA-A, -B and -DRB1 alleles. Pearson Chi
      square or continuity correction or two-sided Fisher's exact test were used. The
      results showed that the genotype frequency of HLA-B*48:01 and DRB1*09:01 were
      significantly higher in children with AA as compared with healthy controls (P <
      0.05). The genotype frequency of HLA-B*51:01, DRB1*03:01 and DRB1*11:01 were
      significantly lower in children with AA as compared with healthy controls (P <
      0.05). Besides, the results also demonstrated that the genotype frequencies of
      HLA-B*48:01 and DRB1*09:01 were significantly higher in SAA as compared with
      controls, the genotype frequencies of B*51:01, DRB1*03:01 and DRB1*11:01 were
      significantly lower in SAA, as compared with controls. In conclusion, HLA-B*48:01
      and DRB1*09:01 are related with children AA, and may be susceptible alleles to
      the development of children AA. Besides, the expression of HLA-B*51:01,
      DRB1*03:01 and DRB1*11:01 are low in children with AA, whether they are relative
      protection alleles of children needs to be further studied.

PMID- 22391181
TI  - [Effect of thalassemia panel reactive antibody on proliferation and apoptosis of
      cord blood CD34(+) cells].
AB  - The study was purposed to explore the effect of panel reactive antibody (PRA)
      serum from patients with beta-thalassemia on proliferation and apoptosis of the
      CD34(+)cells from cord blood and its mechanism. CD34(+) cells of umbilical cord
      blood were incubated with different sera and complement respectively. After
      incubation, the samples were centrifuged and the supernatants were collected for
      lactate dehydrogenase (LDH) detection, and the CD34(+) cells were harvested and
      measured for the apoptosis by flow cytometry with Annexin V/PI. The intracellular
      DNA synthesis were also quantified by [(3)H]TdR incorporation using liquid
      scintillation counter. The results showed that concentration of LDH in PRA
      positive groups was higher as compared with control group, and the DNA synthesis
      of CD34(+) cells in PRA positive groups were inhibited. There were no differences
      in the percentage of cell apoptosis and necrosis among different groups. It is
      concluded that thalassemic serum PRA impairs the cell membrane, inhibits the DNA
      synthesis, which can be increased by addition of the complement, but PRA had no
      significant effect on apoptosis of CD34(+) cells.

PMID- 22391182
TI  - [Bactericidal permeability increasing protein inhibits lipopolysaccharide
      mediated platelet activation in vitro].
AB  - This study was purposed to investigate the inhibitory effect of bactericidal
      permeability-increasing protein (BPI) on lipopolysaccharide (LPS)-mediated
      activation of platelets. Venous blood samples were obtained from 10 healthy
      volunteers and were prepared into platelet-rich plasma (PRP, 1 * 10(8)/ml).
      Experiments were divided into four groups: normal platelet group (untreated
      group); LPS group, BPI group and BPI+LPS group. PRP were stimulated by LPS (10
      ug/ml) in the presence and absence of BPI (100 ug/ml) or BPI alone. Then
      platelets were harvested and determined for Toll-like receptor-4 (TLR-4) with
      flow cytometry (FCM), the supernatant was used for detection of cytokines
      including tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) with
      enzyme-linked immunosorbent assay (ELISA). The results showed that as compared
      with normal platelet group, TLR-4 expression on platelets was significantly
      increased under LPS stimulation (P < 0.001); the levels of TNF-alpha and IL-6 in
      the supernatant were also remarkably elevated (P < 0.001). However, either TLR-4
      expression or the cytokine levels significantly decreased in the presence of BPI
      when platelets underwent LPS-challenge (P < 0.05), but still were higher than
      that in normal platelet group. Stimulating the platelets with BPI alone could not
      enhance the TLR-4 expression and cytokine levels. It is concluded that BPI has
      the ability to inhibit the LPS-induced platelet activation.

PMID- 22391183
TI  - [Effects of transcription factor T-bet, GATA-3, FoxP3 and CD4(+)CD25(+)regulatory
      T cells in pathogenesis of child Hench-Schonlein purpura].
AB  - The aim of this study was to investigate the effects of transcription factors T
      bet, GATA-3 in the pathogenesis of Hench-Schonlein purpura (HSP) in children, the
      relationship between CD4(+)CD25(+)regulatory T cells, transcription factor FoxP3
      and the development of child HSP, and the molecular mechanisms of Th1/Th2
      imbalance of child HSP at acute phase, so as to may provide a new approach and
      strategy for the treatment of HSP at the molecular levels. The expression of T
      bet, GATA-3 and FoxP3 mRNA were detected by real time PCR using SYBR Green I in
      46 patients with HSP at acute phase and 30 healthy children as controls. The
      expression of T lymphocyte subsets CD4(+)CD25(+) in peripheral blood mononuclear
      cells was detected by flow cytometry. The results showed that the relative level
      of GATA-3 mRNA in peripheral blood mononuclear cells of patients with HSP was
      significantly higher than those of the control group (964.30 +/- 655.18 vs 78.09
      +/- 57.20, P < 0.01). The relative level of T-bet mRNA in peripheral blood
      mononuclear cells of patients with HSP was lower than those of the control group
      (53.98 +/- 35.79 vs 181.56 +/- 96.90, P < 0.01). The expression level of FoxP3
      mRNA with HSP was lower than that of the control group (32.17 +/- 23.04 vs 147.91
      +/- 99.15, P < 0.01). The result of CD4(+)CD25(+) Treg with HSP was lower than
      those of the control group [(5.34 +/- 2.51)% vs (7.85 +/- 1.97)%, P < 0.01)]. It
      is concluded that Th1/Th2 imbalance exists in acute phase of child HSP,
      especially predominant activation of Th2, which correlates with the abnormal
      expression of transcription factor T-bet and GATA-3 mRNA. At acute phase of child
      HSP, the expression of CD4(+)CD25(+)Treg and its special transcription factor
      FoxP3 mRNA are down-regulated. Treg cells decreases, which indicates that
      insufficient immunosuppressive effects resulting from the reduction of Treg cells
      may be one of the important reason in the immune imbalance of HSP acute phase.
      This study provides experimental evidence for illustrating the pathogenesis of
      HSP from the molecular mechanism of Treg cells and its regulation, and also
      provides a new thinking and new strategies for the treatment of HSP at molecular
      levels.

PMID- 22391184
TI  - [Homing characteristics of graft cells in leukemia mice after allogenic bone
      marrow transplantation with different conditioning regimens].
AB  - The aim of this study was to investigate the homing characteristics of bone
      marrow cells in leukemia mice after allogenic bone marrow transplantation with
      different conditioning regimens on the basis of a leukemia mouse model. Allogenic
      bone marrow transplantation was performed after three different kinds of
      conditioning regimen, including nonmyeloablative conditioning regimen (5 Gy
      (60)Co gamma ray total body irradiation, A group), radiotherapeutic myeloablative
      conditioning regimen (9 Gy (60)Co gamma ray total body irradiation, B group) and
      chemotherapeutic myeloablative conditioning regimen (large dose chemotherapy, C
      group). In the recipient mice, the nucleated cell number in peripheral blood,
      bone marrow and spleen was counted, the percentage of positive cells capable of
      connecting with FITC labeled anti-mouse H-2K(b) antibody was detected by flow
      cytometry and the homing ratio in bone marrow and spleen was calculated at 24,
      48, 72, 96 h after bone marrow transplantation. The results showed that donor
      myeloid cells displayed homing and then mobilization (going out of home) in group
      A; homing, mobilization, and rehoming in group B and C, and there was a little
      delay of homing in the spleen in group C. In bone marrow, the homing efficiency
      of A group was the highest in early period and the lowest [(0.90 +/- 0.09)%] in
      the fourth day with the mobilization of myeloid cells (P < 0.05), and the homing
      efficiency of B and C groups was lower in the early period and the highest [(2.17
      +/- 0.26)%, B group] in the fourth day with the rehoming of myeloid cells (P <
      0.05). In spleen, the homing efficiency was similar to that in bone marrow and
      there still was a little delay in C group. It is concluded that the homing ratio
      is high in the early period and decrease obviously in 72 h after bone marrow of
      leukemia mice treated with nonmyeloablative conditioning regimen. The homing
      ratio is low in the early period and increases obviously in 72 h after bone
      marrow of leukemia mice treated with radio-or chemotherapeutic myeloablative
      conditioning regimens. The homing ratio does not obviously change between the
      early period and 72 h after bone marrow of leukemia mice treated with
      chemotherapeutic myeloablative conditioning regimen, and lies between group A and
      B.

PMID- 22391185
TI  - [Clinical significance of monitoring BK polyomavirus in patients after
      hematopoietic stem cell transplantation].
AB  - This study was aimed to establish a method for rapid detecting BK polyomavirus
      (BKV) and to investigate the feasibility and value used in leukemia patients
      undergoing hematopoietic stem cell transplantation. Primers were designed
      according to BKV gene sequence; the quantitative standards for BKV and a real
      time fluorescent quantitative PCR for BKV were established. The BKV level in
      urine samples from 36 patients after hematopoietic stem cell transplantation were
      detected by established method. The results showed that the standard of
      reconstructed plasmid and real time fluorescent quantitative PCR method were
      successfully established, its good specificity, sensitivity and stability were
      confirmed by experiments. BKV was found in 55.56% of urine samples, and the BKV
      load in urine was 2.46 * 10(4) - 7.8 * 10(9) copy/ml. It is concluded that the
      establishment of real-time fluorescent quantitative PCR for BKV detection
      provides a method for early diagnosis of the patients with hemorrhagic cystitis
      after hematopoietic stem cell transplantation.

PMID- 22391186
TI  - [Phenotypic identification and differentiation potential analysis of two kinds of
      human amniotic cells].
AB  - The aim of this study was to isolate, cultivate and phenotypically characterize
      two types of human amnio-tic membrane (HAM)-derived cells, and to analyze their
      differentiation potential in vitro. Human amnion epithelial cells (hAEC) were
      derived from the embryonic ectoderm, while human amnion mesenchymal cells (hAMC)
      were derived from the embryonic mesoderm. The cells were characterized by flow
      cytometry and immunofluorescence, then immunofluorescence also was performed for
      the analysis of multipotentiality in differentiation. The results indicated that
      immunophenotypic characterization of both cell types demonstrated positive for
      HLA-A, B, C and mesenchymal stem cell markers (CD29, CD73, CD44, CD59, CD90,
      CD105, CD166), but did not express the hematopoietic markers (CD31, CD34, CD45,
      HLA-DR) and showed the weak expression of costimulatory molecules (CD40, CD40L,
      CD80, CD86). Phenotypes of both cell populations were maintained from passages 3
      to 7. The immunofluorescence indicated that hAEC expressed cytokeratin 19, but
      did not express vimentin. On the contrary, hAMC expressed vimentin but did not
      express cytokeratin 19. The assessment of multilineage potential demonstrated
      that hAMC showed greater cardiomyocytes potential, while hAEC showed greater
      neural potential. It is concluded that hAEC and hAMC can be successfully isolated
      from the HAM. Both cell populations possess similar immunophenotype. However,
      they differ in cell yield and multipotential for differentiation into the major
      lineages, hAEC possess a much greater ectodermal differentiation capacity, while
      hAMC possess a much greater mesodermal differentiation capacity. This conclusion
      will be important for use of these cells in cell therapy.

PMID- 22391187
TI  - [Effect of conditioned medium of mesenchymal stem cells on proliferation,
      migration and adhesion of human umbilical vein endothelial cells].
AB  - The aim of this study was to explore the effect of mesenchymal stem cell (MSC)
      conditioned medium (MSC-CM) on proliferation, migration and adhesion of human
      umbilical vein endothelial cell (CRL1730) and its mechanism. Isolation and
      purification of MSC were performed with the classic adhering method, the surface
      markers (CD29, CD90, CD45 and CD34) in MSC were detected by flow cytometry. MSC
      were treated and cultured for 3 d, the MSC-CM or MSC overexpressing stem cell
      derived factor-1 (SDF-1) conditioned medium (Ad-SDF-1-MSC-CM) were collected.
      Subsequently, CRL1730 cells were treated respectively with 2% FBS-DMEM, 15% FBS
      DMEM (control group), MSC-CM or Ad-SDF-1-MSC-CM for 24 h, the proliferation of
      CRL1730 cells was detected by MTT method. CRL1730 cell migration in vitro was
      performed by using wound healing system. The adhesion ability of CRL1730 cells
      was analyzed by microscope. The results indicated that the CRL1730 cells treated
      with Ad-SDF-1-MSC-CM showed greater proliferative capacity than CRL1730 cells
      treated with MSC-CM. While adding with AMD3100 5 umol/L, the blocker of CXCR4,
      the CRL1730 proliferation mediated by Ad-SDF-1-MSC-CM was significantly reduced.
      Meanwhile, compared with MSC-CM, Ad-SDF-1-MSC-CM had greater effects for
      promoting CRL1730 migration and enhancing adhesion ability of CRL1730 cells,
      these effects were significantly inhibited by AMD3100. It is concluded that MSC
      CM promotes the migration and adhesion ability of CRL1730 cells through SDF-1
      expressed by MSC.

PMID- 22391188
TI  - [Establishment and application of lentivirus luciferase reporter-mediated miRNA
      target gene screening system].
AB  - This study was aimed to establish a high-throughput luciferase reporter system,
      through which to screen and identify miRNAs directly targeting p21, and to
      explore the biological function and significance of these miRNAs. Molecular
      cloning technique was used to construct and identify two lentivirus-expressing
      vectors-pWPXL-Luc and pWPXL-Luc-P21-3'UTR, virus particles were collected after
      the pWPXL-Luc or pWPXL-Luc-P21-3'UTR vectors were co-transfected with the psPAX2
      packaging plasmid and the envelope plasmid pDM2G into HEK-293T cells.
      Furthermore, two stable cell lines expressing luciferase singly or co-expressed
      luciferase and P21-3'UTR were established by transducing HEK-293 cells with
      recombinant lentivirus; the former was used as control in the following
      experiments. Finally luciferase activity of the latter stable cells was measured
      by using the luciferase reporter assay system. The results showed that high-titre
      recombinant lentivirus was produced and two stable cell lines were constructed,
      also to some certain, the luciferase activity was in direct proportion to the
      number of cells. In conclusion, the high-throughput luciferase reporter system is
      established successfully; using this system, the 28 miRNA that directly target
      P21 Cip1/Waf1 are screened experimentally.

PMID- 22391189
TI  - [Construction of venus vector carrying IGFBP7 gene and its expression in K562
      cells].
AB  - The aim of this study was to construct venus vector carrying the gene encoding
      insulin-like growth factor binding protein 7 (IGFBP7), which provides an
      effective platform for exploring the function of this gene in leukemia. After
      digestion by restriction endonuclease, the IGFBP7 gene was recombined with the
      transfer plasmid. The venus particles were packaged using 293T cells to transfect
      K562 cells, and identification was performed by means of flow cytometry, RT-PCR
      and Western blot. The results showed that the sequence of cloned IGFBP7 gene was
      the same as that in GenBank. The size of product restricted by BamHI was same as
      the predicted one. GFP expression was observed in 293T and K562 cells with the
      fluorescent microscopy and flow cytometry. The expression level of mRNA and
      protein of IGFBP7 was confirmed by RT-PCR and Western blotting in K562 cells. It
      is concluded that venus vector carrying IGFBP7 gene has been successfully
      constructed and provides basis for exploring function of IGFBP7 in K562 cells.

PMID- 22391190
TI  - [Construction of lentiviral vector for truncated mouse fibroblast growth factor
      receptor-1 gene and its expression in eukaryotic cells].
AB  - This study was aimed to clone the gene coding mouse fibroblast growth factor
      receptor-1 (fgfr1), to construct the recombinant lentiviral vector of truncated
      form fgfr-1 (Deltafgfr1) carrying enhanced green fluorescence protein (EGFP) and
      to investigate its expression in eukaryotic cells (293FT cells). The full length
      fgfr1 gene was cloned by RT-PCR using brain tissue of BALB/c fetal mouse as
      template and inserted into PCR-Blunt vector, a truncated fgfr1 fragment was
      produced by site-directed mutagenesis for deleting intracellular phosphorylated
      domain, then was subcloned into a lentiviral vector and cotransfected into 293FT
      packaging cells together with envelope plasmid and packaging plasmid by
      lipofectamine 2000. Viruses were gathered and concentrated using ultracentrifuge,
      and then transfected into 293FT cells. Expression of EGFP was detected by
      fluorescent microscopy and flow cytometry (FCM), and the truncated FGFR1 protein
      was detected by Western blot. The results demonstrated that mouse fgfr1 gene was
      cloned and the lentiviral expression vector LV-IRES-EGFP-Deltafgfr1 and control
      vector LV-IRES-EGFP were successfully constructed. The lentiviral particles were
      correctly packaged, and the virus titers were above 10(8) TU/ml in the
      supernatant after concentration. Expression of EGFP was detected by fluorescent
      microscopy in 293FT cells post transfection, and the transfection efficacy was >
      95% determined by FCM. Expression of FGFR1 protein detected by Western blot was
      significantly higher than that in control group. It is concluded that the
      truncated gene fgfr1 along with the gene coding EGFP is successfully inserted
      into a lentiviral vector to construct a recombinant lentiviral vector, which can
      be expressed in eukaryotic cells.

PMID- 22391191
TI  - [Construction of expression vector from different transcripts of RHD gene].
AB  - RHD gene has different alternative transcripts. This study was aimed to construct
      expression vector of normal mRNA, DEL9 and DEL89 transcripts from RHD gene. Total
      RNA was extracted from Rh(D) positive umbilical blood cells of newborn. Intact
      RhD cDNA, DEL9 and DEL89 transcripts were obtained by one-step and two-step RT
      PCR, respectively. The obtained products were cloned into pCR4 TOPO sequencing
      vector for choosing the right transcript. RHD gene was amplified again from the
      sequencing plasmid DNA, and then subcloned into pcDNA3.1/V5-His TOPO expression
      vector; DEL9 and DEL89 were cloned into the expression vector directly. Gene
      sequence and direction were identified by sequencing. The results showed that the
      sequence and direction of target genes were right, thus these 3 different
      expression vectors were correctly constructed. It is concluded that expression
      vector is constructed from different transcripts of RHD gene, which lays a
      foundation for further exploring the membranous protein expression of Rh(D)
      antigen.

PMID- 22391192
TI  - [Discrimination of alleles in HLA-C*07:01:01G and HLA-C*07:02:01G groups through
      detection sequences in exons 1 to 7 of HLA-C locus by using polymerase chain
      reaction sequence-based typing].
AB  - This study was aimed to discriminate the alleles in the HLA-C*07:01:01G and HLA
      C*07:02:01G groups and analyze their associations with HLA-B locus. Samples
      previously typed as HLA-C*07:01:01G and HLA-C*07:02:01G were collected. The
      nucleotide sequences in exons 1 to 7 of the HLA-C locus were sequenced by
      polymerase chain reaction sequence-based typing (PCR-SBT) and HLA-B genotyping
      was also preformed by PCR-SBT in these samples. The results showed that 4 samples
      (30.8%) were confirmed as HLA-C*07:01:01 and 9 samples (69.2%) were HLA-C*07:06
      among 13 samples previously typed as HLA-C*07:01:01G. Linkage disequilibrium (LD)
      analysis showed that HLA-C*07:06 allele was strongly related with HLA-B*44:03.
      All samples were typed as C*07:02:01 among 102 individuals previously typed as
      C*07:02:01G. LD analysis showed that C*07:02:01 was strongly related with HLA
      B*51:01, B*46:01, B*39:01, B*40:01, B*38:02, B*15:02 alleles. It is concluded
      that HLA-C*07:01:01 and HLA-C*07:06 alleles are confirmed in the HLA-C*07:01:01G
      group and HLA-C*07:02:01 is a preferred allele in the HLA-C*07:02:01G.

PMID- 22391193
TI  - [Effect of lentinan against immunosuppression of lymphocytes cultured in
      simulated microgravity environment].
AB  - This study was aimed to evaluate the effect of lentinan on the immune function of
      splenic lymphocytes in rotary cell culture system (RCCS) microgravity
      environment. The splenic lymphocytes from mice were separated and cultured in the
      normal gravity and the microgravity environments. The cells were treated with
      lentinan solution (0, 10, 20 and 40 ug/ml). After incubated with lentinan for
      indicated times (24, 48 and 72 h), the cell proliferation, secretion of cytokine
      and the expression of cell surface markers were detected by MTT method, ELISA and
      flow cytometry respectively. The results indicated that lentinan of above
      mentioned concentrations did not obviously promote the lymphocyte proliferation,
      but increased the secretion of IL-2 and IFN-gamma and enhanced the expression of
      lymphocyte surface markers CD4 and CD8 in microgravity environment. It is
      concluded that lentinan has the ability to enhance the lymphocyte immune function
      in microgravity environment.

PMID- 22391194
TI  - [Experimental study of immunological function regulated by Fufang Hongjingtian
      capsule in mice].
AB  - The aim of this study was to investigate the immunological function regulated by
      Fufang Hongjingtian capsule (HJT) in mice. The mice were given ig HJT 25, 250 and
      750 mg/kg, once daily, for 30 - 38 d, respectively. The mice in control group
      were given ig corresponding solvent. After the last time of administration, the
      immunological parameters of the mice were measured. The results showed that
      compared with negative control group, the delayed type hypersensitivity, spleen
      lymphocyte proliferation and number of spleen IgM antibody forming cells
      increased in HJT groups. In conclusion the HJT has the effect to improve the
      immunological functions of mice.

PMID- 22391195
TI  - [Progress of study on microRNA and chronic myeloid leukemia].
AB  - microRNA (miRNA) are about 22 nucleotide (nt) endogenous small non-coding RNA
      that play an important role in regulation of gene expression at the post
      transcriptional level. miRNA control the expression of genes involved in several
      biologic processes, including apoptosis, proliferation, differentiation and
      metabolism of cells. miRNA can also act as oncogenes or antioncogenes. Abnormal
      expression of miRNA is associated with chronic myelogenous leukemia (CML) and
      contributes to the pathogenesis, disease progression, and response to therapy of
      CML. They may also serve as the potential therapy targets in the disease. In this
      review, the most important findings about the biogenesis pathway and function of
      miRNA as well as the role of miRNA in the pathogenesis, drug-resistance and
      therapy of CML are discussed.

PMID- 22391196
TI  - [Recent research advances on markers, isolation and purification of mouse
      hematopoietic stem cells].
AB  - Hematopoietic stem cells (HSC), the well-characterized adult stem cells both in
      the markers and function, show tremendous therapeutic potential. However, the
      level of hematopoietic stem cells in bone marrow is very low, which makes it
      difficult to work with. Based on cell surface markers and dye staining, HSC can
      be isolated from bone marrow and peripheral blood by using magnetic-activated
      cell separation and fluorescence-activated cell sorting. Over 40 years of
      research, many surface markers have been identified to purify mouse HSC, and
      CD34(-)LSK cells are regarded as the mostly used enrichment of HSC in mouse bone
      marrow. The purpose of this review is to provide insight into the advance of
      these markers, and isolation and purification of HSC.

PMID- 22391197
TI  - [Research advances of genomic GYP coding MNS blood group antigens].
AB  - The MNS blood group system includes more than 40 antigens, and the M, N, S and s
      antigens are the most significant ones in the system. The antigenic determinants
      of M and N antigens lie on the top of GPA on the surface of red blood cells,
      while the antigenic determinants of S and s antigens lie on the top of GPB on the
      surface of red blood cells. The GYPA gene coding GPA and the GYPB gene coding GPB
      locate at the longarm of chromosome 4 and display 95% homologus sequence,
      meanwhile both genes locate closely to GYPE gene that did not express product.
      These three genes formed "GYPA-GYPB-GYPE" structure called GYP genome. This
      review focuses on the molecular basis of genomic GYP and the variety of GYP
      genome in the expression of diversity MNS blood group antigens. The molecular
      basis of Miltenberger hybrid glycophorin polymorphism is specifically expounded.

PMID- 22391198
TI  - [Lenalidomide in hematological malignancies---review].
AB  - Lenalidomide is an immunomodulatory, antiangiogenic drug that is a structural
      analog of thalidomide. Studies showed that lenalidomide may work through various
      mechanisms in hematologic malignancies. These mechanisms involved direct
      cytotoxicity as well as through indirect effects on tumor immunity etc. It is
      approved by the Food and Drug Administration for treatment of multiple myeloma
      and myelodysplastic syndromes, and proved to have a good efficacy. Recent studies
      demonstrate that oral lenalidomide alone produces durable responses with
      manageable adverse events in patients with non-Hodgkin's lymphoma,
      relapsed/refractory Hodgkin's lymphoma, chronic lymphocytic leukemia and older
      patients with acute myeloid leukemia etc, warranting further investigation of
      treatment for these patients. This review focuses the related studies and the
      latest progression about lenalidomide in hematological malignancies in order to
      provide some references and help to the use of lenalidomide for the treatment of
      hematological malignancies.

PMID- 22391199
TI  - [Epigenetic regulation of histone H3 lysine 9 methylation in leukemia].
AB  - In recent years, the role of epigenetic modifications in tumorigenesis drawn more
      and more attention. The aberrant changes of histone modifications have been found
      in leukemias, whereby loss of balance in H3K9 methylation is associated closely
      with leukemogenesis. SUV39H1, the first described histone H3 lysine 9
      methyltransferase takes part in heterochromatin formation and gene transcription
      regulation. It could be a new target for leukemia therapy by correcting the
      aberrance of H3K9 methylation, inducing the reexpression of tumor suppressor
      genes. This review discusses how H3K9 methylation regulating gene transcription,
      silencing gene expression and its association with leukemia.

PMID- 22391200
TI  - [Recent progress of study on imbalance of Th17/Treg cells in aplastic anemia].
AB  - Aplastic anemia (AA) is an autoimmune disease characterized by destruction of
      hematopoietic tissue resulting in hyperfunction of effector T-lymphocytes. Recent
      studies indicate that Th17 and Treg cells are functionally antagonistic each
      other, and the increase of Th17 cells and decrease of Treg cells are closely
      related with AA. In vivo experiments showed that both anti-IL-17 treatment and
      Treg cell infusion can protect against immune-mediated bone marrow failure in
      mouse with AA. This review summarizes the recent progress of study on imbalance
      of Th17/Treg cells in AA, so as to explore the pathogenesis of AA and provide
      approach to clinical treatment. The main problems that are discussed in this
      review include biological characteristics of Th17/Treg cells, the regulation of
      Th17/Treg cell balance and related cytokines, the relationship between Th17/Treg
      cells and AA.

PMID- 22391201
TI  - [New advances of epigenetic study in tumors of lymphatic system---review].
AB  - Epigenetics is aimed to study the heritable changes in gene expression patterns
      independent of alterations in genomic DNA sequence structure, and the mechanisms
      of translation from genotype to phenotype. In recent years, compelling evidence
      gathered supports a role of epigenetic alterations in the pathogenesis of
      lymphatic system tumors. For example, recent data from multiple laboratories
      indicate that several hundred genes, involving dozens of critical molecular
      pathways, are epigenetically suppressed in acute lymphocytic leukemia; a panel of
      methylation markers can be used for additional risk stratification of chronic
      lymphocytic leukemia patients; based on the epigenetic profiles, the class
      prediction models in gray zone lymphoma can be established; the epigenetic
      silencing of microRNAs in multiple myeloma generally appears to have intact P53
      function; epigenetic therapies have broader implication and high potential for
      the development of immunotherapeutic strategies and so on. In this review, the
      latest advances of epigenetic study and the prospect of epigenetic therapy for
      tumors in lymphatic system are summarized.

PMID- 22391202
TI  - [Recent research advances on cryopreserved platelets].
AB  - The right choice of frozen protective agents and additives is an important factor
      to ensure the quality of frozen platelets. The immediate hemostatic function of
      frozen platelet in vivo is superior to liquid-stored platelets. In order to
      ensure the quality of frozen platelets better, it is important to understand the
      role of dimethylsulfoxide (DMSO) in the preservation of frozen platelets and its
      mechanism, and to understand the mechanism of DMSO enhancing the hemostatic
      function of frozen platelets and the effects of different factors on the frozen
      platelets. In this review, the long-term preservation of frozen platelets and its
      quality standards, the mechanism of DMSO effect on the molecular changes and
      inhibition of frozen platelets, different factors influencing preservation
      freezing platelets and the test of preservation effects, the application of
      frozen platelets to the military operation and disaster relief, the canine frozen
      platelet studies and so on are summarized.

PMID- 22391203
TI  - HIV-1 Tat impairs cell cycle control by targeting the Tip60, Plk1 and cyclin B1
      ternary complex.
AB  - HIV-1 Tat triggers intrinsic and extrinsic apoptosis pathways in both infected
      and uninfected cells and plays an important role in the pathogenesis of AIDS.
      Knocking down Tip60, an interactive protein of Tat, leads to the impairment of
      cell cycle progression, indicating a key role of Tip60 in cell cycle control. We
      found that Tip60 interacts with Plk1 through its ZnFMYST domain, and that this
      interaction is enhanced in the G 2/M phase. In addition, cyclin B1 was confirmed
      to interact with the ZnF domain of Tip60. Immunofluorescence imaging showed that
      Tip60 co-localizes with both Plk1 and cyclin B1 at the centrosome during the
      mitotic phase and to the mid-body during cytokinesis. Further experiments
      revealed that Tip60 forms a ternary complex with Plk1 and cyclin B1 and
      acetylates Plk1 but not cyclin B1. HIV-1 Tat likely forms a quaternary complex
      with Tip60, cyclin B1 and Plk1. Fluorescent microscopy showed that Tat causes an
      unscheduled nuclear translocation of both cyclin B1 and Plk1, causing their co
      localization with Tip60 in the nucleus. Tat, Tip60, cyclin B1 and Plk1
      interactions provide new a mechanistic explanation for Tat-mediated cell cycle
      dysregulation and apoptosis.

PMID- 22391204
TI  - Rad18 is a transcriptional target of E2F3.
AB  - The E2F family of transcription factors responds to a variety of intracellular
      and extracellular signals and, as such, are key regulators of cell growth,
      differentiation and cell death. The cellular response to DNA damage is a
      multistep process generally involving the initial detection of DNA damage,
      propagation of signals via posttranslational modifications (e.g., phosphorylation
      and ubiquitination) and, finally, the implementation of a response. We have
      previously reported that E2F3 can be induced by DNA damage, and that it plays an
      important role in DNA damage-induced apoptosis. Here, we demonstrate that E2F3
      knockdown compromises two canonical DNA damage modification events, the
      ubiquitination of H2AX and PCNA. We find that the defect in these
      posttranscriptional modifications after E2F3 knockdown is due to reduced
      expression of important DNA damage responsive ubiquitin ligases. We characterized
      the regulation of one of these ligases, Rad18, and we demonstrated that E2F3
      associates with the Rad18 promoter and directly controls its activity.
      Furthermore, we find that ectopic expression of Rad18 is sufficient to rescue the
      PCNA ubiquitination defect resulting from E2F3 knockdown. Our study reveals a
      novel facet of E2F3's control of the DNA damage response.

PMID- 22391205
TI  - Glycogen synthase kinase (GSK)-3 and mammalian target of rapamycin complex 1
      (mTORC1) cooperate to regulate protein S6 kinase 1 (S6K1).

PMID- 22391206
TI  - Adaptation in a eukaryotic pathway: combining experiments with modeling.

PMID- 22391208
TI  - p38alpha MAPK regulates myocardial regeneration in zebrafish.
AB  - Although adult mammals are unable to significantly regenerate their heart, this
      is not the case for a number of other vertebrate species. In particular,
      zebrafish are able to fully regenerate their heart following amputation of up to
      20% of the ventricle. Soon after amputation, cardiomyocytes dedifferentiate and
      proliferate to regenerate the missing tissue. More recently, identical results
      have also been obtained in neonatal mice. Ventricular amputation of neonates
      leads to a robust regenerative response driven by the proliferation of existing
      cardiomyocytes in a similar manner to zebrafish. However, this ability is
      progressively lost during the first week of birth. The fact that adult zebrafish
      retain the capacity to regenerate their heart suggests that they either possess a
      unique regenerative mechanism, or that adult mammals lose/ inhibit this process.
      p38alpha MUAPK has previously been shown to negatively regulate the proliferation
      of adult mammalian cardiomyocytes. We sought to determine whether a similar
      mechanism exists in adult zebrafish, and whether this needs to be overcome to
      allow regeneration to proceed. To determine whether p38alpha MUAPK also regulates
      zebrafish cardiomyocytes in a similar manner, we generated conditional transgenic
      zebrafish in which either dominant-negative or active p38alpha MUAPK are
      specifically expressed in cardiomyocytes. We found that active p38alpha MUAPK but
      not dominantnegative p38alpha MUAPK blocks proliferation of adult zebrafish
      cardiomyocytes and, consequently, heart regeneration as well. It appears that
      adult zebrafish cardiomyocytes share many characteristics with adult mammalian
      cardiomyocytes, including p38alpha MAPK-mediated cell cycle inhibition. These
      findings raise the possibility that zebrafish-like heart regeneration could be
      achieved in adult mammals.

PMID- 22391207
TI  - Role for Rif1 in the checkpoint response to damaged DNA in Xenopus egg extracts.
AB  - TopBP1 is critical for both DNA replication and checkpoint regulation in
      vertebrate cells. In this study, we have identified Rif1 as a binding partner of
      TopBP1 in Xenopus egg extracts. In addition, Rif1 also interacts with both ATM
      and the Mre11-Rad50-Nbs1 (MRN) complex, which are key regulators of checkpoint
      responses to double-stranded DNA breaks (DSBs). Depletion of Rif1 from egg
      extracts compromises the activation of Chk1 in response to DSBs but not stalled
      replication forks. Removal of Rif1 also has a significant impact on the chromatin
      binding behavior of key checkpoint proteins. In particular, binding of TopBP1,
      ATR and the MRN complex to chromatin containing DSBs is reduced in the absence of
      Rif1. Rif1 interacts with chromatin in a highly regulated and dynamic manner. In
      unperturbed egg extracts, the association of Rif1 with chromatin depends upon
      formation of replication forks. In the presence of DSBs, there is elevated
      accumulation of Rif1 on chromatin under conditions where the activation of ATM is
      suppressed. Taken together, these results suggest that Rif1 plays a dynamic role
      in the early steps of a checkpoint response to DSBs in the egg-extract system by
      promoting the correct accumulation of key regulators on the DNA.

PMID- 22391210
TI  - The cyclin K/Cdk12 complex: an emerging new player in the maintenance of genome
      stability.

PMID- 22391209
TI  - Flavopiridol induces phosphorylation of AKT in a human glioblastoma cell line, in
      contrast to siRNA-mediated silencing of Cdk9: Implications for drug design and
      development.
AB  - Cdk9 and Cdk7 are cdc2-like serine/threonine kinases that stabilize RNA
      transcript elongation through RNA polII carboxyl terminal domain (CTD)
      phosphorylation and are considered suitable targets for cancer therapy.   The
      effects of flavopiridol and of siRNA-mediated inhibition of Cdk9 and/or Cdk7 were
      analyzed in human glioblastoma and human prostate cancer cell lines.   One
      finding revealed that Cdk9 and Cdk7 could substitute each other in RNA polII CTD
      phosphorylation in contrast to the in vitro system. Thus, a simultaneous
      inhibition of Cdk9 and Cdk7 might be required both for targeting malignant cells
      and developing a platform for microarray analysis. However, these two pathways
      are not redundant, as indicated by differential effects observed in cell cycle
      regulation following siRNA-mediated inhibition of Cdk9 and/or Cdk7 in human PC3
      prostate cancer cell line. Specifically, siRNA-mediated inhibition of Cdk9 caused
      a shift from G 0/G 1 to G 2/M phase in human PC3 prostate cancer cell line.  
      Another finding showed that flavopiridol treatment induced a substantial AKT
      Ser473 phosphorylation in human glioblastoma T98G cell line in contrast to siRNA
      mediated inhibition of Cdk9 and Cdk9 combined with Cdk7, whereas siRNA-mediated
      silencing of Cdk7 caused a minor increase in AKT-Ser473 phosphorylation. AKT
      Ser473 is a hallmark of AKT pathway activation and may protect cells from
      apoptosis. This finding also shows that Cdk9 and Cdk7 pathways are not redundant
      and may have important implications in drug development and for studying the
      mechanism of chemoresistance in malignant cells.

PMID- 22391211
TI  - MiR-33 connects cholesterol to the cell cycle.

PMID- 22391212
TI  - Schizophrenia in patients with atopic disorders with particular emphasis on
      asthma: a Danish population-based study.
AB  - OBJECTIVE: Autoimmune diseases and infections have been associated with an
      increased risk of schizophrenia that could be rooted in inflammatory mechanisms.
      However, other diseases characterized by a heightened immune response, such as
      atopic disorders, remain to be thoroughly investigated. The aim of this study was
      to investigate whether atopic disorders in the individual or in a first-degree
      relative affect the risk of developing schizophrenia. METHOD: We linked two
      nationwide population-based registers: the Danish Psychiatric Central Register
      and the National Hospital Register. Two longitudinal designs were used: a cohort
      study and a case/sibling study. Rate ratios (RRs) and accompanying 95% confidence
      intervals (CIs) were obtained. RESULTS: Hospital contact with any atopic disorder
      increased the RR of schizophrenia by 1.45 (95% CI=1.31-1.90). The increased risk
      was mainly driven by asthma: 1.59 (95% CI=1.31-1.90); this was confirmed when
      cases were compared with siblings instead of the background population. Hospital
      contact with other included atopic disorders (atopic dermatitis, urticaria and
      allergic rhinitis) increased the risk of schizophrenia significantly only if they
      were combined into one group. Hospital contact with asthma in a first-degree
      relative did not significantly increase the risk of schizophrenia. CONCLUSION:
      This study indicates the existence of an association between atopic disorders in
      general and asthma in particular and the risk of developing schizophrenia. The
      study adds to a growing body of literature suggesting the possible involvement of
      immune processes in the pathophysiology of schizophrenia.

PMID- 22391213
TI  - Muscarinic M1 receptor sequence: preliminary studies on its effects on cognition
      and expression.
AB  - It has been reported that people with schizophrenia who are homozygous at the
      c.267C>A single nucleotide polymorphism of the cholinergic muscarinic M1 receptor
      (CHRM1) perform less well on the Wisconsin Card Sorting Test than those who are
      heterozygous. We investigated whether CHRM1 sequence is associated with impaired
      executive function, a common problem in schizophrenia. We sequenced the CHRM1
      using peripheral DNA from 97 people with schizophrenia who completed the
      Wisconsin Card Sorting Test, a verbal fluency test and the National Adult Reading
      Test. Clinical severity was assessed using the Positive and Negative Syndrome
      Scale. To determine whether CHRM1 sequence affected receptor expression, we used
      post-mortem data, from another cohort, to investigate associations between CHRM1
      sequence and mRNA levels. On the Wisconsin Card Sorting Test, 267C/C participants
      with schizophrenia made more perseverative errors (p<0.05) and perseverative
      responses (p<0.05) than 267C/A participants. Genotype had no effect on verbal
      fluency (p=0.8) or National Adult Reading test (p=0.62). Cortical CHRM1 mRNA
      levels did not vary with gene sequence (p=0.409). The clinical study supports the
      proposal that CHRM1 sequence is associated with alterations in some aspects of
      executive function. However, the post-mortem study indicates this is not simply
      due to altered expression at the level of mRNA, suggesting this sequence
      alteration may affect the functionality of the CHRM1.

PMID- 22391214
TI  - [Medical errors].

PMID- 22391216
TI  - International note: between-domain relations of Chinese high school students'
      academic achievements.
AB  - The present study examined the between-domain relations of Chinese high school
      students' academic achievements. In a sample of 1870 Chinese 10th grade students,
      the results indicated that Chinese high school students' academic achievements
      were correlated across nine subjects. In line with the previous Western findings,
      the findings suggested that academic achievement was largely domain-general in
      nature.

PMID- 22391215
TI  - Vascular tissues are a primary source of BMP2 expression during bone formation
      induced by distraction osteogenesis.
AB  - Prior studies showed that bone regeneration during distraction osteogenesis (DO)
      was dependent on vascular tissue development and that inhibition of VEGFR
      signaling diminished the expression of BMP2. A combination of micro-computed
      tomography (MUCT) analysis of vascular and skeletal tissues, immunohistological
      and histological analysis of transgenic mice containing a BAC transgene in which
      beta-galactosidase had been inserted into the coding region of BMP2 and qRT-PCR
      analysis, was used to examine how the spatial temporal expression of the
      morphogenetic signals that drive skeletal and vascular tissue development is
      coordinated during DO. These results showed that BMP2 expression was induced in
      smooth muscle and vascular endothelial cells of arteries and veins, capillary
      endothelial cells, hypertrophic chondrocytes and osteocytes. BMP2 was not
      expressed by lymphatic vessels or macrophages. Separate peaks of BMP2 mRNA
      expression were induced in the surrounding muscular tissues and the distraction
      gap and corresponded first with large vessel collateralization and arteriole
      remodeling followed by periods of angiogenesis in the gap region.
      Immunohistological and qRT-PCR analysis of VEGF receptors and ligands showed that
      mesenchymal cells, lining cells and chondrocytes, expressed VEGFA, although PlGF
      expression was only seen in mesenchymal cells within the gap region. On the other
      hand VEGFR2 appeared to be predominantly expressed by vascular endothelial and
      hematopoietic cells. These results suggest that bone and vascular tissue
      formation is coordinated via a mutually supporting set of paracrine loops in
      which blood vessels primarily synthesize the morphogens that promote bone
      formation while mesenchymal cells primarily synthesize the morphogens that
      promote vascular tissue formation.

PMID- 22391217
TI  - Studies on the pathogenesis of a Chinese strain of bovine parainfluenza virus
      type 3 infection in Balb/c mice.
AB  - To date, three genotypes A, B, and C of bovine parainfluenza virus type 3 (BPIV3)
      have been isolated from cattle and only limited studies on the pathogenesis of
      the genotype A of BPIV3 infection in calves and laboratory animals have been
      conducted. The pathogenesis of the genotypes B and C of BPIV3 infection in calves
      and laboratory animals have not been reported. To alleviate the difficulties
      associated with sourcing suitable calves for infection studies, the establishment
      of BPIV3 infection model using laboratory model animals could aid in increasing
      the knowledge of the pathogenesis of this virus. Therefore thirty Balb/c mice
      were intranasally inoculated with a Chinese BPIV3 strain SD0835 which was
      classified as genotype C. Virus replications in mice were demonstrated by using
      virus isolation and titration, immunofluorescent staining, and
      immunohistochemistry and had occurred in the respiratory tissues as early as 24h
      after intranasal inoculation. The results of immunofluorescent staining and IHC
      implicated that the lungs and tracheas might be the major tissues in which the
      SD0835 infected and replicated. The histopathologic examinations revealed that
      alveoli septa thickening and focal cellulose pneumonia were seen in the lungs of
      experimentally infected mice. The aforementioned results indicated that the
      SD0835 of the genotype C was pathogenic to Balb/c mice and the mouse infection
      model could cast light on the genotype C of BPIV3 infection process and
      pathogenesis.

PMID- 22391218
TI  - Probabilistic models of state estimation predict visuomotor transformations
      during prism adaptation.
AB  - This study aims to create a prediction model for state-space estimation and to
      elucidate the required information processing for identifying an external space
      in prism adaptation. Subjects were 57 healthy students. The subjects were
      instructed to rapidly perform reaching movements to one of the randomly
      illuminating light-emitting diode lights. Their movements were measured while
      wearing prism glasses and after removing that. We provided the following four
      conditions and control. In target condition, reaching error distance was visually
      fed back to the subject. In trajectory condition, the trajectory of fingertip
      movement could be seen, and the final reaching error was not fed back. Two
      restricted visual feedback conditions were prepared based on a different
      presentation timing (on-time and late-time conditions). We set up a linear
      parametric model and an estimation model using Kalman filtering. The goodness of
      fit between the estimated and observed values in each model was examined using
      Akaike information criterion (AIC). AIC would be one way to evaluate two models
      with different number of parameters. In the control, the value of AIC was 179.0
      and 154.0 for the linear model and Kalman filtering, respectively, while these
      values were 173.6 and 161.1 for the target condition, 202.8 and 159.7 for the
      trajectory condition, 192.7 and 180.8 for the on-time condition, and 206.9 and
      174.0 for the late-time condition. Kalman gain in the control was 0.07-0.26.
      Kalman gain relies on the prior estimation distribution when its value is below
      0.5. Kalman gain in the trajectory and late-time conditions was 0.03-0.60 and
      0.08-0.95, respectively. The Kalman filter, a state estimation model based on
      Bayesian theory, expressed the dynamics of the internal model under uncertain
      feedback information better than the linear parametric model. The probabilistic
      estimation model can clearly simulate state estimation according to the
      reliability of the visual feedback.

PMID- 22391219
TI  - Reduced mismatch negativity in mild cognitive impairment: associations with
      neuropsychological performance.
AB  - Mild cognitive impairment (MCI) refers to a transitory state between healthy
      aging and dementia. Biomarkers are needed to facilitate early identification of
      MCI and predict progression to dementia. One potential neurophysiological
      biomarker, mismatch negativity (MMN), is an event-related potential reflecting
      fundamental, pre-attentive cognitive processes. MMN is reduced in normal aging
      and dementia and in neuropsychiatric samples and is associated with verbal memory
      deficits and poor executive functioning. This study aimed to investigate auditory
      MMN and its relationship to neuropsychological performance in MCI. Twenty-eight
      MCI participants and fourteen controls, aged >=50 years, underwent
      neurophysiological and neuropsychological assessment, and completed
      questionnaires pertaining to disability. Relative to controls, the MCI group
      demonstrated reduced temporal MMN amplitude (p < 0.01). Reduced right temporal
      MMN was significantly associated with poorer verbal learning (r = 0.496; p <
      0.01) and reduced left temporal MMN was significantly associated with increased
      self-reported disability (r = -0.419; p < 0.05). These results indicate that
      patients with MCI exhibit altered pre-attentive information processing, which in
      turn is associated with memory and psychosocial deficits. These findings overall
      suggest that MMN may be a viable neurophysiological biomarker of underlying
      disease in this 'at risk' group.

PMID- 22391220
TI  - ABCG2- and ABCG4-mediated efflux of amyloid-beta peptide 1-40 at the mouse blood
      brain barrier.
AB  - The accumulation of amyloid-beta peptide (Abeta) in the brain is a critical
      hallmark of Alzheimer's disease. This high cerebral Abeta concentration may be
      partly caused by impaired clearance of Abeta across the blood-brain barrier
      (BBB). The low-density lipoprotein receptor-related protein-1 (LRP-1) and the ATP
      binding cassette (ABC) protein ABCB1 (P-glycoprotein) are involved in the efflux
      of Abeta across the BBB. We hypothesized that other ABC proteins, such as members
      of the G subfamily, are also involved in the BBB clearance of Abeta. We therefore
      investigated the roles of ABCG2 (BCRP) and ABCG4 in the efflux of [3H] Abeta1-40
      from HEK293 cells stably transfected with human ABCG2 or mouse abcg4. We showed
      that ABCG2 and Abcg4 mediate the cellular efflux of [3H] Abeta1-40. In addition,
      probucol fully inhibited the efflux of [3H] Abeta1-40 from HEK293-abcg4 cells.
      Using the in situ brain perfusion technique, we showed that GF120918 (dual
      inhibitor of Abcb1 and Abcg2) strongly enhanced the uptake (Clup, MUl/g/s) of
      [3H] Abeta1-40 by the brains of Abcb1-deficient mice, but not by the brains of
      Abcb1/Abcg2-deficient mice, suggesting that Abcg2 is involved in the transport of
      Abeta at the mouse BBB. Perfusing the brains of Abcb1/Abcg2- and Abca1-deficient
      mice with [3H] Abeta1-40 plus probucol significantly increased the Clup of Abeta.
      This suggests that a probucol-sensitive transporter that is different from Abca1,
      Abcb1, and Abcg2 is involved in the brain efflux of Abeta. We suggest that this
      probucol-sensitive transporter is Abcg4. We conclude that Abcg4 acts in concert
      with Abcg2 to efflux Abeta from the brain across the BBB.

PMID- 22391222
TI  - Emerging avenues linking inflammation and cancer.
AB  - The role of inflammation in carcinogenesis has been extensively investigated and
      well documented. Many biochemical processes that are altered during chronic
      inflammation have been implicated in tumorigenesis. These include shifting
      cellular redox balance toward oxidative stress; induction of genomic instability;
      increased DNA damage; stimulation of cell proliferation, metastasis, and
      angiogenesis; deregulation of cellular epigenetic control of gene expression; and
      inappropriate epithelial-to-mesenchymal transition. A wide array of
      proinflammatory cytokines, prostaglandins, nitric oxide, and matricellular
      proteins are closely involved in premalignant and malignant conversion of cells
      in a background of chronic inflammation. Inappropriate transcription of genes
      encoding inflammatory mediators, survival factors, and angiogenic and metastatic
      proteins is the key molecular event in linking inflammation and cancer. Aberrant
      cell signaling pathways comprising various kinases and their downstream
      transcription factors have been identified as the major contributors in abnormal
      gene expression associated with inflammation-driven carcinogenesis. The
      posttranscriptional regulation of gene expression by microRNAs also provides the
      molecular basis for linking inflammation to cancer. This review highlights the
      multifaceted role of inflammation in carcinogenesis in the context of altered
      cellular redox signaling.

PMID- 22391221
TI  - Docosahexaenoic acid-induced unfolded protein response, cell cycle arrest, and
      apoptosis in vascular smooth muscle cells are triggered by Ca2+-dependent
      induction of oxidative stress.
AB  - Proliferation of vascular smooth muscle cells is a characteristic of pathological
      vascular remodeling and represents a significant therapeutic challenge in several
      cardiovascular diseases. Docosahexaenoic acid (DHA), a member of the n-3
      polyunsaturated fatty acids, was shown to inhibit proliferation of numerous cell
      types, implicating several different mechanisms. In this study we examined the
      molecular events underlying the inhibitory effects of DHA on proliferation of
      primary human smooth muscle cells isolated from small pulmonary artery (hPASMCs).
      DHA concentration-dependently inhibited hPASMC proliferation, induced G1 cell
      cycle arrest, and decreased cyclin D1 protein expression. DHA activated the
      unfolded protein response (UPR), evidenced by increased mRNA expression of HSPA5,
      increased phosphorylation of eukaryotic initiation factor 2alpha, and splicing of
      X-box binding protein 1. DHA altered cellular lipid composition and led to
      increased reactive oxygen species (ROS) production. DHA-induced ROS were
      dependent on both intracellular Ca(2+) release and entry of extracellular Ca(2+).
      Overall cellular ROS and mitochondrial ROS were decreased by RU360, a specific
      inhibitor of mitochondrial Ca(2+) uptake. DHA-induced mitochondrial dysfunction
      was evidenced by decreased mitochondrial membrane potential and decreased
      cellular ATP content. DHA triggered apoptosis as found by increased numbers of
      cleaved caspase-3- and TUNEL-positive cells. The free radical scavenger Tempol
      counteracted DHA-induced ROS, cell cycle arrest, induction of UPR, and apoptosis.
      We conclude that Ca(2+)-dependent oxidative stress is the central and initial
      event responsible for induction of UPR, cell cycle arrest, and apoptosis in DHA
      treated hPASMCs.

PMID- 22391223
TI  - Zero field splitting parameters of Mn2+ in Bis (L-asparaginato) Zn (II) at
      interstitial orthorhombic symmetry site.
AB  - The superposition model is used to calculate the crystal field parameters (CFPs)
      of Mn(2+) in Bis (L-asparaginato) Zn (II). The zero field splitting parameters
      (ZFSPs) D and E are then investigated using perturbation theory and microscopic
      spin Hamiltonian (SH) theory. The calculated ZFS parameters are compared with the
      experimental values obtained by electron paramagnetic resonance. Both the zero
      field splitting parameters (ZFSPs) D and E evaluated theoretically are in good
      agreement with the experimental values. The results support the notion that the
      Mn(2+) ion occupies interstitial site in Bis (L-asparaginato) Zn (II).

PMID- 22391224
TI  - Growth, spectral, optical, thermal, crystallization perfection and nonlinear
      optical studies of novel nonlinear optical crystal--urea thiosemicarbazone
      monohydrate.
AB  - Single crystals of organic nonlinear material urea thiosemicarbazone monohydrate
      (UTM) have been grown by slow evaporation method. The grown crystals were
      characterized by single crystal X-ray diffraction analysis reveals that sample
      crystallized in triclinic system with noncentrosymmetric space group P1. Powder
      XRD pattern confirmed that grown crystal posses highly crystalline nature. FTIR
      spectrum was recorded to identify the presence of functional groups and molecular
      structure was confirmed by (1)H NMR spectrum. Material confirmation of title
      compound has been performed by using mass spectroscopic analysis. Elemental
      composition of grown crystal was confirmed by energy-dispersive spectrometry
      (EDS). To study the crystalline perfection of the grown crystals, high-resolution
      X-ray diffraction (HR-XRD) study was carried out. Thermogravimetric and
      differential thermal analyses were employed to understand the thermal and physio
      chemical stability of the synthesized compound. UV-Vis-NIR spectrum revealed the
      transmission properties of the crystal specimen. Relative SHG efficiency is
      measured by Kurtz and Perry method and found to about 0.89 times that of standard
      potassium dihydrogen phosphate (KDP) crystals.

PMID- 22391225
TI  - Non invasive analysis of miniature paintings: proposal for an analytical
      protocol.
AB  - The characterisation of palettes used in manuscript illumination is a hard
      analytical task, due to value and fragility of the analysed items. Analysis on
      miniatures must be necessarily non-invasive and fast and requires the use of
      several techniques since no single technique is able to provide all information
      needed. In this work a four-step analytical protocol is proposed for non-invasive
      in situ characterisation of miniature paintings. The protocol allows the
      identification of coloured materials through the use in sequence of complementary
      techniques, so as to fully exploit the information given by each instrument.
      Preliminarily to the instrumental investigations on ancient books and miniatures
      is the compilation of spectroscopic databases obtained from "standard" samples
      prepared on parchment, according to recipes described in medieval artistic
      treatises. The protocol starts with an extensive investigation with UV-visible
      spectrophotometry in reflectance mode, collecting spectra from all the most
      significant painted areas in the manuscript; chemometric classification is then
      performed on the spectra to highlight areas possibly containing the same
      materials. The second step involves in-depth inspection of miniatures under
      optical microscopy that guides the interpretation of reflectance spectra. XRF
      spectrometry is then performed to characterise pigments and metal layers, to
      verify the presence of overlapping layers, to identify mordants in lakes and to
      recognise minor components that may yield information concerning provenance; in
      addition, chemometric classification can be performed on element concentrations
      to highlight similar areas. Finally, Raman spectroscopy is used to shed light on
      the uncertain cases, if still present. Such a procedure offers a wealth of
      information without causing stress to the manuscripts under analysis.

PMID- 22391226
TI  - Development and validation of a method for allantoin determination in liposomes
      and pharmaceutical formulations.
AB  - The aim of this work was to develop and validate an ultraviolet derivative
      spectrophotometric (UVDS) method for the quantitative determination of allantoin
      (ALL) in liposomes, gels and creams. Liposomes were prepared by methods of thin
      film hydration and mechanical agitation. Solutions of ALL in 0.1 mol/L NaOH with
      ethanol:water (70:30, v/v) were prepared in order to destroy liposome vesicles.
      Spectral interference from components of liposomes, cream, gel and ALL
      degradation products was eliminated using the second-order derivative of the zero
      order spectrum. Characterization of ALL in 0.1 mol/L NaOH was carried out by
      direct infusion mass spectrometry. Absorbances of ALL solutions were measured at
      266.6 nm of the second-derivative spectrum and linearity was observed in the ALL
      concentration range of 50-300 MUgmL(-1) (correlation coefficient (r)=0.9961). The
      mean recovery percentage was 100.68 +/- 1.61, repeatability expressed as relative
      standard deviation (RSD) was 1.07 and 2.12%, and intermediate precision (RSD) was
      2.16%. The proposed UVDS method was found to be linear, precise, accurate, robust
      and selective, providing rapid and specific determination of ALL in raw materials
      and in topical formulations.

PMID- 22391227
TI  - Differential domain structure stability of the severe acute respiratory syndrome
      coronavirus papain-like protease.
AB  - Papain-like protease (PLpro) from severe acute respiratory syndrome (SARS)
      coronavirus is one of the two proteases involved in the proteolytic processing of
      the virion polyproteins. In addition, PLpro shows significant in vitro
      deubiquitinating and de-ISGylating activities. All these findings demonstrated
      the multifunctional nature of the PLpro. Here we report the sensitivity of PLpro
      to denaturant urea. An increase in urea concentration induced a reversible
      biphasic unfolding of the enzyme. Differently, the unfolding of the catalytic
      triad region located within the palm and thumb domains followed a monophasic
      unfolding curve. Further observations suggest that the zinc-binding domain may
      start to unfold during the first transition. An 80% lost of its enzymatic
      activity at a urea concentration lower than 1M showed a close correlation with
      unfolding of the zinc-binding domain. The enzyme was also characterized in terms
      of hydrophobicity and size-and-shape distribution. We have demonstrated that
      PLpro displayed differential domain structure stability and molten globule state
      in its folding. These studies will not only assist in our understanding of the
      folding of this viral enzyme, but also that of other deubiquitinating enzymes
      with a similar scaffold.

PMID- 22391228
TI  - Screening of integrin-binding peptides from the laminin alpha4 and alpha5 chain G
      domain peptide library.
AB  - Laminins, a multifunctional protein family of extracellular matrix, interact with
      various types of integrin. Here, integrin-mediated cell adhesive peptides have
      been systematically screened in the laminin alpha4 and alpha5 chain G domain
      peptide library consisting of 211 peptides by both the peptide-coated plastic
      plates and peptide-conjugated Sepharose bead assays using human dermal
      fibroblasts. Thirteen peptides promoted cell spreading and the activity was
      specifically inhibited by EDTA. Cell attachment to 11 peptides was inhibited by
      anti-integrin beta1 antibody. Additionally, cell attachment to the A5G81
      (AGQWHRVSVRWG) and A5G84 (TWSQKALHHRVP) peptides was specifically inhibited by
      anti-integrin alpha3 and alpha6 antibodies. These results suggest that the A5G81
      and A5G84 peptides promote integrin alpha3beta1- and alpha6beta1-mediated cell
      attachment. Further, most of the integrin-mediated cell adhesive peptides are
      located in the loop regions in the G domains, suggesting that structure is
      important for the integrin specific recognition. Integrin binding peptides are
      useful for understanding laminin functions and have a potential to use for
      biomaterials and drug development.

PMID- 22391229
TI  - Effects of MDMA (ecstasy) and two of its metabolites on rat embryos in vitro.
AB  - MDMA consumers are young people of childbearing age. Consequently, developmental
      exposure to this drug is a potential public health concern. Several studies have
      addressed MDMA neurotoxicity in adults; however, knowledge of the effects of MDMA
      on developing embryos is limited. After administration, MDMA is metabolized
      species specifically via two main pathways. One leads to the formation of MDA and
      the other to the formation of HHMA. Here we evaluated the embryotoxic effects of
      MDMA, and also those of MDA, a main metabolite of MDMA in rats, and HHMA, a main
      metabolite in humans. For this purpose, we used the whole embryo culture (WEC).
      Our results show a concentration-dependent embryotoxic effect of MDMA, MDA and
      HHMA at a concentration range of 25-50MUg/ml. The embryotoxic potential of the
      parent compound and the two metabolites was comparable in vitro.

PMID- 22391230
TI  - Immunogenicity of recombinant human erythropoietin in Korea: a two-year cross
      sectional study.
AB  - Immunogenicity of erythropoietin (EPO) is related with pure red cell aplasia
      (PRCA). We sought to determine the prevalence of antibody (Ab)-mediated PRCA in
      Korea and threshold diagnostic criteria by dual parameters: Ab titer and
      neutralizing activity. This study was a multi-center, cross-sectional study for
      two years. In the first year study (1 YS), 209 samples suspected to be EPO
      resistance were collected. In the second year study (2 YS), all the patients who
      consented to participate (N = 946) were enrolled. In 1 YS, we found three and six
      serum samples that were positive and borderline for anti-EPO Abs, respectively.
      The first three patients had neutralizing activity (NT) and were diagnosed as
      PRCA. In 2 YS, seven patients were anti-EPO positives and six had borderline
      levels. Among them, one patient with NT was diagnosed as PRCA and one with NT as
      aplastic anemia. The prevalence of PRCA was 0.106%. The correlation analysis of
      the 22 patients who had anti-EPO Ab showed that dual crossed cut-off lines (anti
      EPO Ab titer >= 40 ng/ml, % NT >= 25%) were able to clearly isolate red cell
      aplasia. We suggest novel diagnostic criteria for diagnosis and prediction of Ab
      mediated PRCA with data from both Ab titer assays and NT bioassays.

PMID- 22391231
TI  - Investigation of efficient features for image recognition by neural networks.
AB  - In the paper, effective and simple features for image recognition (named LiRA
      features) are investigated in the task of handwritten digit recognition. Two
      neural network classifiers are considered-a modified 3-layer perceptron LiRA and
      a modular assembly neural network. A method of feature selection is proposed that
      analyses connection weights formed in the preliminary learning process of a
      neural network classifier. In the experiments using the MNIST database of
      handwritten digits, the feature selection procedure allows reduction of feature
      number (from 60 000 to 7000) preserving comparable recognition capability while
      accelerating computations. Experimental comparison between the LiRA perceptron
      and the modular assembly neural network is accomplished, which shows that
      recognition capability of the modular assembly neural network is somewhat better.

PMID- 22391232
TI  - Evolving neural fields for problems with large input and output spaces.
AB  - We have developed an extension of the NEAT neuroevolution method, called
      NEATfields, to solve problems with large input and output spaces. The NEATfields
      method is a multilevel neuroevolution method using externally specified design
      patterns. Its networks have three levels of architecture. The highest level is a
      NEAT-like network of neural fields. The intermediate level is a field of
      identical subnetworks, called field elements, with a two-dimensional topology.
      The lowest level is a NEAT-like subnetwork of neurons. The topology and
      connection weights of these networks are evolved with methods derived from the
      NEAT method. Evolution is provided with further design patterns to enable
      information flow between field elements, to dehomogenize neural fields, and to
      enable detection of local features. We show that the NEATfields method can solve
      a number of high dimensional pattern recognition and control problems, provide
      conceptual and empirical comparison with the state of the art HyperNEAT method,
      and evaluate the benefits of different design patterns.

PMID- 22391233
TI  - PMOG: the projected mixture of Gaussians model with application to blind source
      separation.
AB  - We extend the mixtures of Gaussians (MOG) model to the projected mixture of
      Gaussians (PMOG) model. In the PMOG model, we assume that q dimensional input
      data points z(i) are projected by a q dimensional vector w into 1-D variables
      u(i). The projected variables u(i) are assumed to follow a 1-D MOG model. In the
      PMOG model, we maximize the likelihood of observing u(i) to find both the model
      parameters for the 1-D MOG as well as the projection vector w. First, we derive
      an EM algorithm for estimating the PMOG model. Next, we show how the PMOG model
      can be applied to the problem of blind source separation (BSS). In contrast to
      conventional BSS where an objective function based on an approximation to
      differential entropy is minimized, PMOG based BSS simply minimizes the
      differential entropy of projected sources by fitting a flexible MOG model in the
      projected 1-D space while simultaneously optimizing the projection vector w. The
      advantage of PMOG over conventional BSS algorithms is the more flexible fitting
      of non-Gaussian source densities without assuming near-Gaussianity (as in
      conventional BSS) and still retaining computational feasibility.

PMID- 22391234
TI  - A morphological perceptron with gradient-based learning for Brazilian stock
      market forecasting.
AB  - Several linear and non-linear techniques have been proposed to solve the stock
      market forecasting problem. However, a limitation arises from all these
      techniques and is known as the random walk dilemma (RWD). In this scenario,
      forecasts generated by arbitrary models have a characteristic one step ahead
      delay with respect to the time series values, so that, there is a time phase
      distortion in stock market phenomena reconstruction. In this paper, we propose a
      suitable model inspired by concepts in mathematical morphology (MM) and lattice
      theory (LT). This model is generically called the increasing morphological
      perceptron (IMP). Also, we present a gradient steepest descent method to design
      the proposed IMP based on ideas from the back-propagation (BP) algorithm and
      using a systematic approach to overcome the problem of non-differentiability of
      morphological operations. Into the learning process we have included a procedure
      to overcome the RWD, which is an automatic correction step that is geared toward
      eliminating time phase distortions that occur in stock market phenomena.
      Furthermore, an experimental analysis is conducted with the IMP using four
      complex non-linear problems of time series forecasting from the Brazilian stock
      market. Additionally, two natural phenomena time series are used to assess
      forecasting performance of the proposed IMP with other non financial time series.
      At the end, the obtained results are discussed and compared to results found
      using models recently proposed in the literature.

PMID- 22391236
TI  - Spatial and temporal variations in coral growth on an inshore turbid reef
      subjected to multiple disturbances.
AB  - Coral growth rates (linear extension, density, calcification rates) of three fast
      growing corals (Acropora, Montipora, Turbinaria) were studied in situ on Middle
      Reef, an inshore reef located on the central Great Barrier Reef (GBR), to assess
      the influence of changing environmental conditions on coral condition and reef
      growth. Middle Reef is subjected to both local (e.g. high sediment loads) and
      global (e.g. coral bleaching) disturbance events, usually associated with reduced
      coral growth. Results indicated, however, that Acropora growth rates (mean linear
      extension = 6.3 cm/year) were comparable to those measured at similar depths on
      offshore reefs on the GBR. Montipora linear extension (2.9 cm/year) was greater
      than estimates available from both clear-water and turbid reefs, and Turbinaria's
      dense skeleton (1.3 g/cm(3)) may be more resilient to physical damage as ocean pH
      falls. Coral growth was found to vary between reef habitats due to spatial
      differences in water motion and sediment dynamics, and temporally with lower
      calcification rates during the summer months when SSTs (monthly average 29 
      degrees C) and rainfall (monthly total >500 mm) were high. In summary, corals on
      Middle Reef are robust and resilient to their marginal environmental conditions,
      but are susceptible to anthropogenic disturbances during the summer months.

PMID- 22391235
TI  - p97/VCP- and Lys48-linked polyubiquitination form a new signaling pathway in DNA
      damage response.
AB  - RNF8/RNF168-dependent Lys63-linked polyubiquitination at sites of DNA double
      strand breaks (DSBs) was originally regarded as the sole ubiquitin-signaling
      pathway involved in the DNA damage response (DDR). However, ubiquitin-dependent
      p97/VCP segregase activity and RNF8-dependent Lys48-linked polyubiquitin chains
      at DSB sites have recently been identified as components of an additional and
      parallel ubiquitin-signaling DDR pathway. This newly identified pathway is
      essential to spatiotemporal protein turnover and regulates both main branches of
      DSB repair, homologous recombination and nonhomologous end joining. In this
      report, the function of the RNF8/Lys48 polyubiquitin chains/p97 pathway is
      discussed in the context of DSB repair and p97 chromatin-related functions.

PMID- 22391237
TI  - Toxic effects of engineered nanoparticles in the marine environment: model
      organisms and molecular approaches.
AB  - Engineered nanoparticles (ENPs) have been produced by nano-biotech companies in
      recent decades to generate innovative goods in various fields, including
      agriculture, electronics, biomedicine, manufacturing, pharmaceuticals and
      cosmetics. The nano-scale size of the particles can confer novel and
      significantly improved physical, chemical and biological properties to scientific
      phenomena and processes. As their applications to science and technology expand,
      the need to understand the putative noxious effects of ENPs on humans and
      ecosystems is becoming increasingly important. ENPs are emerging as a new class
      of pollutants with eco-toxicological impacts on marine ecosystems because the
      particles can end up in waterways and reach the sea. Recent laboratory studies in
      invertebrates and fishes suggest that exposure to ENPs could have harmful
      effects. Because there is not much data available for gauging the effects of ENPs
      on marine wildlife, the ultimate ecotoxicological impacts of chronic exposure to
      ENPs should be investigated further using laboratory tests and field studies. We
      propose the use of model organisms to understand the molecular pathways involved
      in the mechanisms that may be affected by exposure to ENPs. Sensitive and
      innovative molecular methods will provide information regarding the hazards of
      ENPs that may exist in the marine environment. Model organisms that have not been
      conventionally used for risk assessment and the development of eco-toxicogenomic
      approaches will result in an improved understanding of the mechanistic modes of
      action of contaminating ENPs in the marine environment.

PMID- 22391239
TI  - The synthetic progestogen, Levonorgestrel, but not natural progesterone, affects
      male mate calling behavior of Xenopus laevis.
AB  - Worldwide, more than 100 million women use hormonal contraceptives, which act
      through progestogenic modes of action. These man-made hormones can enter the
      aquatic environment as they are excreted via feces and urine. Xeno-progestins are
      able to interfere with the endocrine system of female aquatic vertebrates
      impairing oogenesis and reproduction. However, data on progestogenic effects on
      reproductive behavior of male aquatic vertebrates are lacking. To evaluate
      whether progestins affect the mating behavior of male Xenopus laevis, we exposed
      male frogs to three environmentally relevant concentrations (10(-7) M, 10(-8) M
      and 10(-10) M) of the synthetic progestin Levonorgestrel (LNG) and the
      corresponding natural steroid progesterone (PRG), respectively. LNG at all
      exposure concentrations increased the proportions of advertisement calling,
      indicating a sexually aroused state of the males. Furthermore LNG at 10(-7) M
      decreased the relative proportions of rasping, a call type indicating a sexually
      unaroused state of the male. PRG, on the other hand, did not affect any of those
      parameters. Temporal and spectral features of the advertisement call itself were
      not affected by any of the two exposure treatments. Since LNG exhibits slight
      androgenic activity, the results suggest that LNG effects on male mate calling
      behavior of X. laevis are due to its moderate androgenic but not to its
      progestogenic activities. However, although males' sexual arousal seems to be
      enhanced by LNG, the adverse effects of LNG on female reproduction presumably
      outweigh these enhancing effects and LNG exposure nonetheless might result in
      reduced reproductive success of these animals.

PMID- 22391238
TI  - Gonadotropin-inhibitory hormone (GnIH): discovery, progress and prospect.
AB  - A hypothalamic neuropeptide, gonadotropin-releasing hormone (GnRH), is the
      primary factor regulating gonadotropin secretion. An inhibitory hypothalamic
      neuropeptide for gonadotropin secretion was, until recently, unknown, although
      gonadal sex steroids and inhibin can modulate gonadotropin secretion. Findings
      from the last decade, however, indicate that GnRH is not the sole hypothalamic
      regulatory neuropeptide of vertebrate reproduction, with gonadotropin-inhibitory
      hormone (GnIH) playing a key role in the inhibition of reproduction. GnIH was
      originally identified in birds and subsequently in mammals and other vertebrates.
      GnIH acts on the pituitary and on GnRH neurons in the hypothalamus via a novel G
      protein-coupled receptor (GPR147). GnIH decreases gonadotropin synthesis and
      release, inhibiting gonadal development and maintenance. Such a down-regulation
      of the hypothalamo-pituitary-gonadal (HPG) axis may be conserved across
      vertebrates. Recent evidence further indicates that GnIH operates at the level of
      the gonads as an autocrine/paracrine regulator of steroidogenesis and
      gametogenesis. More recent evidence suggests that GnIH also acts both upstream of
      the GnRH system and at the level of the gonads to appropriately regulate
      reproductive activity across the seasons and during times of stress. The
      discovery of GnIH has fundamentally changed our understanding of hypothalamic
      control of reproduction. This review summarizes the discovery, progress and
      prospect of GnIH, a key regulator of vertebrate reproduction.

PMID- 22391241
TI  - The Rho kinase pathway regulates the migration of dendritic cells through SIRP
      alpha.

PMID- 22391240
TI  - Multi-layered environmental regulation on the homeostasis of stem cells: the saga
      of hair growth and alopecia.
AB  - Stem cells are fascinating because of their potential in regenerative medicine.
      Stem cell homeostasis has been thought to be mainly regulated by signals from
      their adjacent micro-environment named the "stem cell niche". However, recent
      studies reveal that there can be multiple layers of environmental controls. Here
      we review these environmental controls using the paradigm of hair stem cells,
      because to observe and analyze the growth of hair is easier due to their
      characteristic cyclic regeneration pattern. The length of hair fibers is
      regulated by the duration of the growth period. In the hair follicles, hair stem
      cells located in the follicle bulge interact with signals from the dermal
      papilla. Outside of the follicle, activation of hair stem cells has been shown to
      be modulated by molecules released from the intra-dermal adipose tissue as well
      as body hormone status, immune function, neural activities, and aging. The
      general physiological status of an individual is further influenced by circadian
      rhythms and changing seasons. The interactive networks of these environmental
      factors provide new understanding on how stem cell homeostasis is regulated,
      inspiring new insights for regenerative medicine. Therapies do not necessarily
      have to be achieved by using stem cells themselves which may constitute a higher
      risk but by modulating stem cell activity through targeting one or multiple
      layers of their micro- and macro-environments.

PMID- 22391242
TI  - The effects of NB-UVB on the hair follicle-derived neural crest stem cells
      differentiating into melanocyte lineage in vitro.
AB  - BACKGROUND: Narrow-band UVB (NB-UVB) is an effective therapeutic option in the
      treatment of vitiligo. Despite the apparent clinical efficacy, the underlying
      mechanism of how topical NB-UVB induces repigmentation in vitiligo has not been
      clearly elucidated. OBJECTIVES: To investigate the effects of NB-UVB on the
      maturation of melanocyte lineage differentiated from hair follicle-derived neural
      crest stem cells (HF-NCSCs) in vitro. METHODS: HF-NCSCs were isolated from mouse
      whisker follicles. The isolated cells were multipotent and expressed embryonic
      NCSC biomarkers. The effects of NB-UVB on development and differentiation of HF
      NCSCs were evaluated. We assessed cell viability, melanogenesis and migration of
      melanocytes derived from HF-NCSCs after NB-UVB radiation. Tyrosinase, Tyrp1, Dct,
      Kit, Mc1R, Fzd4, NT3R, Ednra, EP1, TGFbetaR, Sox10, Mitf, Lef1 and Pax3 gene
      expression was measured by quantitative RT-PCR, while Tyrosinase, Sox10 and Mitf
      protein expression were measured by Western blot analysis. Cell migration was
      measured by Boyden chamber transwell assay. RESULTS: NB-UVB increased the
      expression of tyrosinase during melanocytic differentiation from mouse HF-NCSCs,
      however, NB-UVB inhibited proliferation of melanocytes derived from HF-NCSCs.
      Mechanistically, increased melanocyte maturation after NB-UVB treatment was
      resulted from increased expression of several key melanogenic factors, including
      Sox10, Kit and Mc1R, which play a critical role to promote tyrosinase expression.
      Furthermore, the migration of the HF-NCSCs-derived melanocytes was downregulated
      as NB-UVB doses increased. However, the migration of HF-NCSCs was upregulated
      under 0.4J NB-UVB radiation. CONCLUSIONS: Those data provide in vitro evidence
      demonstrating some direct effects of NB-UVB on pigmentation of melanocyte lineage
      differentiated from HF-NCSCs, and may provide a possible mechanism for the effect
      of NB-UVB in vitiligo.

PMID- 22391243
TI  - Correlation between serum thymus and activation-regulated chemokine levels and
      stratum corneum barrier function in healthy individuals and patients with mild
      atopic dermatitis.
AB  - BACKGROUND: Serum thymus and activation-regulated chemokine (TARC) levels closely
      reflect the disease activity of atopic dermatitis (AD). AD is characterized by
      impaired epidermal barrier function and atopic dry skin. However, dry skin is
      also a very common problem in healthy individuals. OBJECTIVE: To investigate the
      relationship between serum TARC levels and epidermal barrier function in healthy
      subjects and patients with mild AD. METHODS: This study included 2 groups, 121
      healthy subjects (healthy group) and 66 patients with mild AD (mild AD group).
      Barrier function was assessed by transepidermal water loss (TEWL) and stratum
      corneum hydration (SCH). RESULTS: Significantly elevated serum TARC levels and
      TEWL values and significantly decreased SCH values were detected in the mild AD
      group compared to those in the healthy group. In the mild AD group, serum TARC
      levels were significantly correlated with TEWL values and were inversely
      correlated with SCH values. Importantly, serum TARC levels were also inversely
      correlated with SCH values in the healthy controls. TEWL values in the healthy
      group tended to be correlated with TARC levels but did not reach statistical
      significance. CONCLUSION: Together with TEWL and SCH, serum TARC level is a
      useful biomarker, reflecting impairment of epidermal function in AD patients as
      well as healthy subjects.

PMID- 22391245
TI  - Visual signal processing in the macaque lateral geniculate nucleus.
AB  - Comparisons of S- or prepotential activity, thought to derive from a retinal
      ganglion cell afferent, with the activity of relay cells of the lateral
      geniculate nucleus (LGN) have sometimes implied a loss, or leak, of visual
      information. The idea of the "leaky" relay cell is reconsidered in the present
      analysis of prepotential firing and LGN responses of color-opponent cells of the
      macaque LGN to stimuli varying in size, relative luminance, and spectral
      distribution. Above a threshold prepotential spike frequency, called the signal
      transfer threshold (STT), there is a range of more than 2 log units of test field
      luminance that has a 1:1 relationship between prepotential- and LGN-cell firing
      rates. Consequently, above this threshold, the LGN cell response can be viewed as
      an extension of prepotential firing (a "nonleaky relay cell"). The STT level
      decreased when the size of the stimulus increased beyond the classical receptive
      field center, indicating that the LGN cell is influenced by factors other than
      the prepotential input. For opponent ON cells, both the excitatory and the
      inhibitory response decreased similarly when the test field size increased beyond
      the center of the receptive field. These findings have consequences for the
      modeling of LGN cell responses and transmission of visual information,
      particularly for small fields. For instance, for LGN ON cells, information in the
      prepotential intensity-response curve for firing rates below the STT is left to
      be discriminated by OFF cells. Consequently, for a given light adaptation, the
      STT improves the separation of the response range of retinal ganglion cells into
      "complementary" ON and OFF pathways.

PMID- 22391244
TI  - Characterization of retinoic acid-inducible gene-I (RIG-I) expression
      corresponding to viral infection and UVB in human keratinocytes.
AB  - BACKGROUND: Retinoic acid-inducible gene-I (RIG-I) is a cytoplasmic protein that
      recognizes viral double-stranded RNA to induce the type I interferon (IFN)
      response. In human keratinocytes, RIG-I is induced by IFN-gamma and tumor
      necrosis factor-alpha stimulation, and is abundantly expressed in psoriatic
      keratinocytes of the spinous and basal layers. OBJECTIVE: This study investigated
      the effects of extraneous stimuli including viral infection and UVB exposure on
      RIG-I expression in human keratinocytes. METHODS: Human skin keratinocytes (HaCaT
      cells) were stimulated by polyinosinic-polycytidylic acid (poly(I:C)), which
      mimics viral infection, and UVB exposure. We assessed the expression of RIG-I and
      IFN-regulatory factor (IRF)-1 in HaCaT cells by RT-PCR and Western blot analysis.
      Moreover, we investigated the effect of IRF-1 binding site of RIG-I gene promoter
      on the regulation of RIG-I expression by luciferase promoter assay and
      electrophoretic mobility shift assay. RESULTS: Poly(I:C) induced RIG-I
      expression, while UVB inhibited basal RIG-I expression and the poly(I:C)-induced
      RIG-I overexpression in HaCaT cells. IRF-1, which binds to a regulatory element
      located on the RIG-I gene promoter, was required for both inductions of RIG-I
      expression. IRF-1 expression was enhanced three hours after the poly(I:C)
      stimulation, consistent with the RIG-I response to poly(I:C), and thereafter was
      suppressed. Moreover, UVB exposure promptly decreased IRF-1 expression, resulting
      in decreased IRF-1 protein binding to the RIG-I promoter, and consequently,
      decreased RIG-I expression. CONCLUSION: Thus, suppression of RIG-I and IRF-1
      expression caused by UVB exposure may partly explain the inhibition of skin-based
      immune responses, leading to viral infection and recrudescence.

PMID- 22391246
TI  - Differential susceptibility to the PPAR-gamma agonist pioglitazone in 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine rodent models of
      Parkinson's disease.
AB  - A growing body of evidence suggests that peroxisome proliferator-activated
      receptor (PPAR) agonists are valuable candidates as disease modifiers in
      Parkinson's disease (PD) and may thus enable neuroprotection and preserve motor
      function. The present study sought to evaluate the effect of the PPAR-gamma
      agonist pioglitazone in two different animal models of PD. The study was based on
      nigral dopaminergic neuron labelling and the assessment of motor behaviour in (i)
      the frequently investigated MPTP mouse model and (ii) the less well-known
      bilateral 6-OHDA rat model. In MPTP-injected mice, pioglitazone reversed body
      weight loss and the reduction in rearing frequency and induced significant
      neuroprotection of the nigrostriatal dopaminergic pathway (by 24%, compared with
      vehicle). In contrast, pioglitazone did not have any effect on the 73.5% loss of
      dopaminergic neurons or motor impairments (a reduced rearing frequency and a loss
      of strength in the forepaws) in bilateral 6-OHDA rats. The PPAR-gamma agonist
      pioglitazone had a significant neuroprotective effect in MPTP mice but not in
      bilateral 6-OHDA rats. The various effects of PPAR agonists in both models can be
      accounted by the different action mechanism of the 2 toxins or by the fact that
      3MUg 6-OHDA injection was too harmful to be alleviated by the compound. This work
      supports PPAR-agonists to be relevant in the therapeutic strategy research in
      Parkinson's disease and highlights the importance in evaluating neuroprotective
      agent in different models.

PMID- 22391247
TI  - Are novel serum biomarkers informative?
AB  - To justify use in routine coronary heart disease (CHD) risk assessment, a novel
      serum biomarker must be specifically associated with future CHD events and add
      information beyond techniques currently available. Current risk assessment
      techniques are probabilistic and imperfect; however, to date, no novel serum
      biomarker has improved substantially on the current population-based risk
      stratification approach. Although limited trial-based data are available to
      assess the utility of biomarkers, insights gained from biomarkers may enhance
      clinical decision making. Continued basic science and population-based research
      into CHD biomarkers may help to further the capacity for CHD risk assessment.

PMID- 22391248
TI  - LDL cholesterol: the lower the better.
AB  - High cholesterol is often a prerequisite for atherosclerotic plaque. Low-density
      lipoprotein cholesterol (LDL-C) is the focus of the National Cholesterol
      Education Program Adult Treatment Panel guidelines. LDL-C ranges from 50 to 70
      mg/dL in native hunter-gatherers, healthy human neonates, free-living primates,
      and other wild mammals, who are notably free of atherosclerotic vascular disease.
      Multiple statin trials and meta-analyses support a treatment target of LDL-C
      levels less than 70 mg/dL, as this is associated with improved clinical outcomes
      and atherosclerosis regression. In fact, no threshold has yet been identified
      below which patients do not benefit from lowering of LDL-C.

PMID- 22391249
TI  - HDL-cholesterol: perfection is the enemy of good?
AB  - An inverse relationship between the plasma concentration of high-density
      lipoprotein (HDL)-cholesterol and the risk of having a cardiovascular event has
      been shown in several epidemiologic studies. It is likely that this relationship
      is causal because HDL has several intrinsic properties that can potentially
      reverse atherosclerosis. However, this has not been conclusively shown in humans,
      and trying to achieve perfection with pharmacotherapy is possibly the enemy of
      good (ie, a healthy lifestyle). Patients with low HDL should be advised to change
      their lifestyle, including smoking cessation, weight reduction, and regular
      exercise.

PMID- 22391250
TI  - Triglycerides: how much credit do they deserve?
AB  - In the modern era of statin therapy, major advances have been made in treating
      coronary heart disease. However, despite intensive treatment with statin therapy,
      residual cardiovascular risk persists and has been attributed to the persistence
      of atherogenic dyslipidemia and, in part, elevated triglycerides (TGs). In this
      review, the authors focus on the mechanism of elevated TGs and provide a
      discussion of the challenges of measuring TGs as a biomarker, its role in the
      pathogenesis of atherosclerotic heart disease, and results of several recent
      studies that have elucidated the relationship between TGs and cardiovascular
      morbidity and mortality.

PMID- 22391251
TI  - Atherosclerosis in chronic kidney disease: lessons learned from glycation in
      diabetes.
AB  - In diabetes, glycation is a nonenzymatic posttranslational modification resulting
      from the bonding of a sugar molecule with a protein or lipid followed by
      oxidation, resulting in the development of advanced glycation end products (AGE).
      Like glycation, carbamylation is a posttranslational protein modification that is
      associated with AGE formation. Glycation of extracellular matrix proteins and low
      density lipoprotein with subsequent deposition in the vessel wall could
      contribute to inflammatory response and atheroma formation. It is logical to
      extrapolate that carbamylation may result in modification of vessel wall proteins
      similar to glycation, and predispose to atherosclerosis.

PMID- 22391252
TI  - "My parents died of myocardial infarction: is that my destiny?".
AB  - This article presents an overview of clinical and molecular genetics of
      myocardial infarction (MI). Discussion includes the partial overlapping of risk
      factors for myocardial infarction and atherosclerosis, the impact of a positive
      family history on the risk of MI, the "familial" nongenetic, environmental
      factors, the inherited risk associated with the low-dose input of many genes, and
      a simple approach to stratify the individual risk in genetic counseling.

PMID- 22391253
TI  - Age as a risk factor.
AB  - The risk of developing cardiovascular disease (CVD) is generally dependent on the
      presence or absence of traditional risk factors. Age is a well-known traditional
      risk factor, generally considered nonmodifiable. This review discusses the common
      use of individual age in prediction of CVD incidence using different risk scores,
      whether or not age as a risk factor can be modified, the methods used to evaluate
      long-term and short-term CVD risk, appropriate communication of individual risk
      based on age group and CVD risk, and the influence of age on cardiac and vascular
      risk factors.

PMID- 22391254
TI  - Coronary artery disease in aging women: a menopause of endothelial progenitor
      cells?
AB  - The cardiovascular protection provided to women during the reproductive age and
      the unique angiogenic properties of the female reproductive system provide
      insights into the complex regulatory network of female sex hormones, angiogenic
      growth factors, and stem cell regulatory molecules. The intricate and interwoven
      endometrial physiology of the female menstrual cycle shows that in order to
      harness the physiologic cardioprotection provided by nature to women of
      reproductive age, for better cardiovascular therapies in postmenopausal women and
      the population in general, a coherent and systematic approach is needed.

PMID- 22391255
TI  - Imaging for prevention.
AB  - Cardiovascular disease deaths have declined considerably, with more than 35%
      reductions during the past two decades, yet a sizable detection gap remains.
      Cardiovascular disease remains the leading cause of morbidity and mortality in
      the United States and across the world, including in developing and developed
      nations. Recent statistics reveal that approximately 840,000 deaths were
      attributed to cardiovascular disease, approximately 300,000 more deaths than
      reported for cancer; three-quarters were reported in previously asymptomatic
      individuals, raising the question as to whether screening for cardiovascular
      disease is warranted in detecting potentially high-risk patients.

PMID- 22391256
TI  - Genomics: is it ready for primetime?
AB  - The next decade will focus on identifying the missing heritability of coronary
      artery disease (CAD). This process will involve a more comprehensive
      interrogation of common single nucleotide polymorphisms (SNPs) that impart modest
      biologic effect and an interrogation of rare SNPs that impart profound biologic
      effect. In parallel, an investigation of the underlying biology of the described
      association will likely yield novel pathways that provide therapeutic targets.
      Once we obtain a more complete inventory of sequence variation that predisposes
      to CAD, a more realistic assessment of the role of genetic risk scoring allied
      with standard risk algorithms will be possible.

PMID- 22391257
TI  - Statins personalized.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor medications, commonly
      referred to as statins, are among the most widely prescribed medications.
      Variation in individual response to statins concerning low-density lipoprotein
      cholesterol reduction, clinical event benefit, and side effects has been
      observed. Some of this variability is attributed to demographic and environmental
      issues, chief of which is compliance. A large portion of the individual response
      to statin therapy is attributed to single nucleotide polymorphisms that have
      recently been elucidated, several of which seem to have clinical utility.

PMID- 22391258
TI  - Childhood cholesterol disorders: the iceberg base or nondisease?
AB  - Pediatric cholesterol disorders are common, affecting 1 in 5 adolescents,
      although most are mild or moderate abnormalities. Because cholesterol values
      during childhood are moderately predictive of adult cholesterol levels, and are
      associated with atherosclerosis by pathology and by vascular testing, and because
      familial hyperlipidemias are associated with early cardiovascular events,
      cholesterol screening is recommended during childhood. Identified lipid
      abnormalities are an indication for lifestyle improvement and, in rare cases,
      pharmacotherapy. However, many gaps in the pediatric knowledge base remain about
      the benefits and risk, the optimal method for lipid screening, and about
      appropriate indications for pharmacotherapy.

PMID- 22391259
TI  - Risk factor update: old wine in a new bottle?

PMID- 22391261
TI  - Molecular profiling of paired helical filaments.

PMID- 22391260
TI  - Local renin-angiotensin systems in the adrenal gland.
AB  - In the adrenal gland all components of the renin-angiotensin system (RAS) are
      expressed in both the adrenal cortex and the adrenal medulla. In this review
      evidence shall be presented that a local secretory RAS exists in the adrenal
      cortex that stimulates aldosterone production and serves as an amplification
      system for circulating angiotensin (ANG) II. The regulation of the secretory
      adrenal RAS clearly differs from the regulation of the circulatory RAS in terms
      of renin expression as well as of renin secretion. For example under potassium
      load the activity of the renal and circulatory RAS is suppressed whereas the
      activity of the adrenal RAS is stimulated. Thus the activity of the adrenal RAS
      but not of the circulating RAS correlates well with the regulation of aldosterone
      production by potassium. The present review also summarizes the knowledge about
      the expression and functions of an additional renin transcript that has recently
      been discovered. This transcript encodes for a non-secretory cytosolic renin
      isoform. The cytosolic renin may be a basis for the existence of an intracellular
      renin system in the adrenal gland that has long been proposed. The present state
      of knowledge shall be discussed indicating that such an intracellular system
      modulates cell survival and cell death such as apoptosis and necrosis or cell
      functions such as aldosterone production.

PMID- 22391264
TI  - The cartilage matrix molecule components produced by human foetal cartilage
      rudiment cells within scaffolds and the role of exogenous growth factors.
AB  - Development of cartilage lesions in osteoarthritis and following traumatic injury
      has important consequences on the weight bearing and articulation of joints, has
      severe impact on the quality of life of affected individuals and is of
      significant socioeconomic impact. Hyaline cartilage is a highly specialised
      tissue with a limited ability to self repair. Development of three-dimensional
      scaffolds which maintain the correct chondrocyte phenotype during expansion of
      cells in vitro and their application in regenerative strategies for cartilage
      repair is therefore a major research objective of many laboratories. This study
      examined the matrix components elaborated by cultured foetal cartilage rudiment
      cells, a mixture of chondroblasts/chondroprogenitor cells and committed
      chondrocytes, in monolayer, cell pellet cultures and in the synthetic scaffolds
      sodium alginate and polyglycolic acid (PGA). The ability of fibroblast growth
      factor (FGF)-2 and FGF-18 to promote chondrogenesis in pellet cultures was also
      examined. While the scaffolds did not completely replicate the matrix
      organisation evident in native cartilage, type II collagen and aggrecan were
      nevertheless prominent matrix components. FGF-2 and FGF-18 further promoted the
      production of cartilage-specific matrix components in pellet culture as FGF-18
      stimulated the production of type X collagen and perlecan and may be indicative
      of a more terminally differentiated phenotype induced in the rudiment cells with
      this growth factor.

PMID- 22391265
TI  - Lipid multilayer microarrays for in vitro liposomal drug delivery and screening.
AB  - Screening for effects of small molecules on cells grown in culture is a well
      established method for drug discovery and testing, and faster throughput at lower
      cost is needed. Small-molecule arrays and microfluidics are promising approaches.
      Here we introduce a simple method of surface-mediated delivery of drugs to cells
      from a microarray of phospholipid multilayers (layers thicker than a bilayer)
      encapsulating small molecules. The multilayer patterns are of sub-cellular
      dimensions and controllable thickness and were formed by dip-pen nanolithography.
      The patterns successfully delivered a rhodamine-tagged lipid and drugs only to
      the cells directly over them, indicating successful encapsulation and no cross
      contamination to cells grown next to the patterns. We also demonstrated
      multilayer thickness-dependant uptake of the lipids from spots with sub-cellular
      lateral dimensions, and therefore the possibility of delivering different dosages
      from different areas of the array. The efficacies of two drugs were assayed on
      the same surface, and we were able to deliver dosages comparable to those of
      solution based delivery (up to the equivalent of 30 MUg/mL). We expect our method
      to be a promising first step toward producing a single high-throughput liposome
      based screening microarray plate that can be used in the same way as a standard
      well plate.

PMID- 22391266
TI  - Asian dust storm events are associated with an acute increase in pneumonia
      hospitalization.
AB  - PURPOSE: This study aims to examine the association of Asian dust storm (ADS)
      events with the daily number of pneumonia admissions using 10-year population
      based data in the Taipei metropolitan region. METHODS: We identified 1,933,247
      admissions with a principal discharge diagnosis of pneumonia between 2000 and
      2009. The auto-regressive integrated moving average (ARIMA) method was used to
      examine the associations between ADS episodes and the logarithm of the daily
      number of pneumonia hospitalizations. RESULTS: There was a significant difference
      in the mean number of daily pneumonia admissions between ADS event days, post-ADS
      event days, and non-ADS event days (P < .001); the mean number of daily
      admissions for ADS event days, post-ADS event days, and non-ADS event days were
      292.5, 305.7, and 279.0, respectively. After adjusting for the time-trend effect,
      ambient temperature, and SO(2), CO, and O(3), the ARIMA showed that compared with
      non-ADS event days, ADS event days and post-ADS event days 1 through 4 had a
      significantly higher mean number of pneumonia admissions for the total group.
      CONCLUSIONS: Our results suggest that ADS event days and post-ADS days 1 through
      4 had significantly higher mean numbers of pneumonia admissions than non-ADS
      days.

PMID- 22391267
TI  - Nonsignificance plus high power does not imply support for the null over the
      alternative.
AB  - This article summarizes arguments against the use of power to analyze data, and
      illustrates a key pitfall: Lack of statistical significance (e.g., p > .05)
      combined with high power (e.g., 90%) can occur even if the data support the
      alternative more than the null. This problem arises via selective choice of
      parameters at which power is calculated, but can also arise if one computes power
      at a prespecified alternative. As noted by earlier authors, power computed using
      sample estimates ("observed power") replaces this problem with even more
      counterintuitive behavior, because observed power effectively double counts the
      data and increases as the P value declines. Use of power to analyze and interpret
      data thus needs more extensive discouragement.

PMID- 22391268
TI  - Dehydroepiandrosterone (DHEA) inhibits voltage-gated T-type calcium channels.
AB  - BACKGROUND AND PURPOSE: Dehydroepiandrosterone (DHEA) and its sulfated form,
      DHEAS, are the most abundant steroid hormones in the mammalian blood flow. DHEA
      may have beneficial effects in various pathophysiological conditions such as
      cardiovascular diseases or deterioration of the sense of well-being. However to
      date, the cellular mechanism underlying DHEA action remains elusive and may
      involve ion channel modulation. In this study, we have characterized the effect
      of DHEA on T-type voltage-activated calcium channels (T-channels), which are
      involved in several cardiovascular and neuronal diseases. KEY RESULTS: Using the
      whole-cell patch-clamp technique, we demonstrate that DHEA inhibits the three
      recombinant T-channels (Ca(V)3.1, Ca(V)3.2 and Ca(V)3.3) expressed in NG108-15
      cell line, as well as native T-channels in pulmonary artery smooth muscle cells.
      This effect of DHEA is both concentration (IC(50) between 2 and 7MUM) and voltage
      dependent and results in a significant shift of the steady-state inactivation
      curves toward hyperpolarized potentials. Consequently, DHEA reduces window T
      current and inhibits membrane potential oscillations induced by Ca(V)3 channels.
      DHEA inhibition is not dependent on the activation of nuclear androgen or
      estrogen receptors and implicates a PTX-sensitive Gi protein pathway.
      Functionally, DHEA and the T-type inhibitor NNC 55-0396 inhibited KCl-induced
      contraction of pulmonary artery rings and their effect was not cumulative.
      CONCLUSIONS: Altogether, the present data demonstrate that DHEA inhibits T
      channels by a Gi protein dependent pathway. DHEA-induced alteration in T-channel
      activity could thus account for its therapeutic action and/or physiological
      effects.

PMID- 22391269
TI  - Bedside chest radiography.
AB  - The bedside chest x-ray (CXR) is an indispensible diagnostic tool for monitoring
      seriously ill patients in the intensive care unit. The CXR often reveals
      abnormalities that may not be detected clinically. In addition, bedside CXRs are
      an irreplaceable tool with which to detect the malposition  of tubes and lines
      and to identify associated complications. Although the image quality is often
      limited, bedside CXRs still provide valuable diagnostic information. The
      interpretation of the bedside CXRs is often challenging, and requires extensive
      radiologic experience to avoid misinterpretation  of the wide spectrum of pleural
      and pulmonary disease. The clinical information is of substantial value for the
      interpretation of the frequently nonspecific findings.

PMID- 22391270
TI  - Does prophylactic CPAP have any role in thoracic surgery?

PMID- 22391271
TI  - The globalization of respiratory care.

PMID- 22391273
TI  - Melatonin and mitochondrial dysfunction in the central nervous system.
AB  - Cell death and survival are critical events for neurodegeneration, mitochondria
      being increasingly seen as important determinants of both. Mitochondrial
      dysfunction is considered a major causative factor in Alzheimer's disease (AD),
      Parkinson's disease (PD) and Huntington's disease (HD). Increased free radical
      generation, enhanced mitochondrial inducible nitric oxide (NO) synthase activity
      and NO production, and disrupted electron transport system and mitochondrial
      permeability transition, have all been involved in impaired mitochondrial
      function. Melatonin, the major secretory product of the pineal gland, is an
      antioxidant and an effective protector of mitochondrial bioenergetic function.
      Both in vitro and in vivo, melatonin was effective to prevent oxidative
      stress/nitrosative stress-induced mitochondrial dysfunction seen in experimental
      models of AD, PD and HD. These effects are seen at doses 2-3 orders of magnitude
      higher than those required to affect sleep and circadian rhythms, both
      conspicuous targets of melatonin action. Melatonin is selectively taken up by
      mitochondria, a function not shared by other antioxidants. A limited number of
      clinical studies indicate that melatonin can improve sleep and circadian rhythm
      disruption in PD and AD patients. More recently, attention has been focused on
      the development of potent melatonin analogs with prolonged effects which were
      employed in clinical trials in sleep-disturbed or depressed patients in doses
      considerably higher than those employed for melatonin. In view that the relative
      potencies of the analogs are higher than that of the natural compound, clinical
      trials employing melatonin in the range of 50-100mg/day are needed to assess its
      therapeutic validity in neurodegenerative disorders.

PMID- 22391272
TI  - Quantifying the severity of acute lung injury using dead-space ventilation:
      should the lung injury score be updated?

PMID- 22391274
TI  - ANZJP this month.

PMID- 22391275
TI  - Neither euthanasia nor suicide, but rather assisted death.

PMID- 22391276
TI  - Explanations and unexplanations: restoring meaning to psychiatry.

PMID- 22391277
TI  - The science and practice of lithium therapy.
AB  - INTRODUCTION: Despite more that 60 years of clinical experience, the effective
      use of lithium for the treatment of mood disorder, in particular bipolarity, is
      in danger of becoming obsolete. In part, this is because of exaggerated fears
      surrounding lithium toxicity, acute and long-term tolerability and the
      encumbrance of life-long plasma monitoring. Recent research has once again
      positioned lithium centre stage and amplified the importance of understanding its
      science and how this translates to clinical practice. OBJECTIVE: The aim of this
      paper is to provide a sound knowledge base as regards the science and practice of
      lithium therapy. METHOD: A comprehensive literature search using electronic
      databases was conducted along with a detailed review of articles known to the
      authors pertaining to the use of lithium. Studies were limited to English
      publications and those dealing with the management of psychiatric disorders in
      humans. The literature was synthesized and organized according to relevance to
      clinical practice and understanding. RESULTS: Lithium has simple pharmacokinetics
      that require regular dosing and monitoring. Its mechanisms of action are complex
      and its effects are multi-faceted, extending beyond mood stability to
      neuroprotective and anti-suicidal properties. Its use in bipolar disorder is
      under-appreciated, particularly as it has the best evidence for prophylaxis,
      qualifying it perhaps as the only true mood stabilizer currently available. In
      practice, its risks and tolerability are exaggerated and can be readily minimized
      with knowledge of its clinical profile and judicious application. CONCLUSION:
      Lithium is a safe and effective agent that should, whenever indicated, be used
      first-line for the treatment of bipolar disorder. A better understanding of its
      science alongside strategic management of its plasma levels will ensure both
      wider utility and improved outcomes.

PMID- 22391278
TI  - The role of alprazolam for the treatment of panic disorder in Australia.
AB  - OBJECTIVE: To investigate the potential impact of increasing prescription rates
      of alprazolam for the treatment of panic disorder (PD) in Australia through a
      review of efficacy, tolerability and adverse outcome literature. METHODS: Data
      were sourced by a literature search using MEDLINE, Embase, PsycINFO and a manual
      search of scientific journals to identify relevant articles. Clinical practice
      guidelines from the American Psychiatric Association, National Institute of
      Clinical Excellence, Royal Australian and New Zealand College of Psychiatrists
      and World Federation of Societies of Biological Psychiatry were sourced.
      Prescription data were sourced from Australian governmental sources. RESULTS:
      Alprazolam has shown efficacy for control of PD symptoms, particularly in short
      term controlled clinical trials, but is no longer recommended as a first-line
      pharmacological treatment due to concerns about the risks of developing
      tolerance, dependence and abuse potential. Almost no evidence is available
      comparing alprazolam to current first-line pharmacological treatment. Despite
      this, prescription rates are increasing. A number of potential issues including
      use in overdose and impact on car accidents are noted. conclusion: Although
      effective for PD symptoms in clinical trials, a number of potential issues may
      exist with use. Consideration of its future place in PD treatment in Australia
      may be warranted.

PMID- 22391279
TI  - Transitioning patients taking clozapine from the public to private/GP shared-care
      setting: barriers and criteria.
AB  - OBJECTIVE: The aim of this study was to explore the barriers to transitioning
      patients taking clozapine from the public to private psychiatrist or general
      practitioner (GP) shared-care setting, as well as the criteria used by staff to
      identify patients suitable for transitioning. METHOD: The experience of
      clinicians managing people taking clozapine was explored through circulation of a
      feedback questionnaire. The clozapine transition questionnaire (CTQ) was
      developed as the primary measure following extensive consultation with clinical
      staff with expertise in clozapine treatment. A total of 215 clinicians were sent
      questionnaires (60 community mental health service staff, 120 private
      psychiatrists registered to prescribe clozapine, and 35 GPs from the Bayside
      Health clozapine GP shared-care programme), with overall 80 (46.2%) returned.
      RESULTS: Over 64% of participants had managed patients who had been transitioned
      from public to private psychiatrist or GP shared-care settings. Around half of
      these said that it was a 'worthwhile treatment option' and that 'it went
      smoothly' and 'the patient was satisfied'. The most significant barriers to
      successful transitioning were the cost of private service, the patient's level of
      disorganization, and the need for ongoing care coordination. The most important
      criteria for transitioning patients was compliance with medication, ability to
      independently attend appointments and access appropriate pharmacies to receive
      medication, and willingness to transition out of the public system. CONCLUSIONS:
      Transitioning suitable public psychiatric patients taking clozapine into private
      psychiatrist/GP shared-care offers an important model to improve the efficiency
      and effectiveness of care, but requires careful planning, preparation, and
      monitoring to ensure sustained success.

PMID- 22391280
TI  - Stereotaxic localisation of the dorsolateral prefrontal cortex for transcranial
      magnetic stimulation is superior to the standard reference position.
AB  - OBJECTIVE: To determine whether the standard method of localisation of the
      dorsolateral prefrontal cortex for repetitive transcranial magnetic stimulation
      is accurate and reliable, and to develop an empirically based method for
      operational localisation of the dorsolateral prefrontal cortex with reference to
      the motor hand area. METHOD: We compared stereotaxic localisation of the
      dorsolateral prefrontal cortex with the commonly used operational definition of 6
      cm anterior to the site of the abductor pollicis brevis muscle in healthy
      participants (n = 18). We also report the average translational distance from the
      site of the abductor pollicis brevis to the stereotaxically defined dorsolateral
      prefrontal cortex. RESULTS: The stereotaxic method was less variable than the
      operational method of localisation and more frequently targeted the middle
      frontal gyrus. The average translational distance from the site of the abductor
      pollicis brevis to the stereotaxically targeted dorsolateral prefrontal cortex
      was x = -5 mm, y = 53 mm and z = -31 mm. CONCLUSIONS: Operational localisation of
      the dorsolateral prefrontal cortex for repetitive transcranial magnetic
      stimulation with reference to the motor hand area is more variable than
      stereotaxic localisation. If future studies choose to use an operational
      definition of the left dorsolateral prefrontal cortex, we suggest it should be 5
      mm lateral, 53 mm anterior and 31 mm inferior to the site of the abductor
      pollicis brevis.

PMID- 22391281
TI  - Duration of assertive community treatment and the interpretation of routine
      outcome data.
AB  - OBJECTIVE: Statistical inferences based on routine outcome monitoring data are
      susceptible to biases. Because this process may be influenced by differences in
      attrition and treatment duration, we wished to gain an insight into the
      relationship between treatment duration and clinical outcome. METHOD: We enrolled
      569 assertive community treatment (ACT) team patients. As part of a six-monthly
      routine outcome monitoring (ROM) procedure, we used the Global Assessment of
      Functioning (GAF) scale, the Health of the Nation Outcome Scales (HoNOS), and a
      scale to assess their treatment motivation and satisfaction with services.
      Duration of ACT showed that treatment duration was short for 292 patients [<=
      three ROM assessments; 11.6 months (SD = 6.1)], medium for 191 [four to six ROM
      assessments; 26.9 months (SD = 7.3)], and long for 86 [>= seven ROM assessments;
      44.06 months (SD=7.1)]. Chi-square and ANOVA were used to compare patient
      characteristics and baseline values across different treatment duration groups,
      and structural equation modelling was used to unravel interdependencies between
      the baseline and outcome variables. RESULTS: More patients receiving long-term
      ACT were diagnosed with a psychotic disorder and/or substance abuse than those
      whose treatment was shorter. Patients whose treatment lasted longer had worse
      baseline GAF and HoNOS scores than those whose treatment was shorter. Structural
      equation modelling showed that the interdependencies between determinants and
      outcome variables (concerning the relationships between both identical and non
      identical variables over time) were different for each of the treatment duration
      categories. CONCLUSIONS: Patients in ACT teams with different treatment durations
      constitute distinguishable groups with different outcomes. This should be taken
      into account when using outcome data for benchmarking purposes.

PMID- 22391282
TI  - The impact of gender on early ill-health retirement in people with heart disease
      and depression.
AB  - OBJECTIVE: Depression and heart disease are major causes of early ill-health
      retirement. The effect of comorbid depression on the award of ill-health
      retirement in those with heart disease is unclear, however, and may differ by
      gender. Given the deleterious effects of ill-health retirement, identifying at
      risk groups is important for guiding targeted interventions. METHOD: We
      retrospectively analysed baseline data of 20,655 participants from the 45 and Up
      Study (New South Wales, Australia), who had fully retired between the ages of 45
      and 64. We examined the associations of depression and heart disease with ill
      health retirement and then adjusted for the presence of common confounders. We
      then restricted the sample to the 1165 individuals with heart disease prior to
      retirement, to determine the impact of comorbid depression on IHR and analysed
      whether there was a differential impact by gender. RESULTS: In the complete
      sample, 3836 out of 20,655 (18.6%) of the participants retired early due to ill
      health. Prior heart disease and depression were both independently and strongly
      associated with ill-health retirement. Those who retired due to ill health were
      also more likely to be men, less educated, report greater physical disability and
      were younger at retirement. Among the 1165 for whom heart disease predated any
      form of retirement, 40% retired due to ill health. Comorbid depression prior to
      ill-health retirement was strongly associated with an increased risk of this IHR
      in women (odds ratio = 2.85; 95% confidence interval = 1.20-6.77, p = 0.01), but
      not in men (interaction term, p = 0.045). CONCLUSIONS: Ill-health retirement is
      common in those with heart disease. Women appear to be particularly susceptible
      to the effects of comorbid depression. Given the policy emphasis on reducing the
      number of people leaving the workforce early, women with early heart disease may
      represent a particular group in whom interventions designed to detect and treat
      comorbid depression should be targeted.

PMID- 22391283
TI  - Repetitive transcranial magnetic stimulation in combination with citalopram in
      young patients with first-episode major depressive disorder: a double-blind,
      randomized, sham-controlled trial.
AB  - OBJECTIVES: To evaluate the effectiveness of repetitive transcranial magnetic
      stimulation (rTMS) started with citalopram in first-episode young major
      depressive patients. METHODS: In a 2-week double-blind study with a 2-week
      extended antidepressant phase, 60 first-episode young major depressive patients
      were randomly assigned to citalopram in combination with 2 weeks of either active
      or sham rTMS treatment. During the following 2 weeks, the patients continued only
      the citalopram treatment. The 17-item Hamilton depression rating scale (HAMD-17)
      and Montgomery-Asberg depression rating scale (MADRS) were used to assess the
      severity of depression. Moreover, the Wisconsin Card Sorting Test (WCST), Trail
      Making Test (TMT), and Stroop Color-Word Test (SCWT) were used to assess
      executive function. RESULTS: (1) There was a significantly greater number of
      early improvers (a reduction of HAMD-17 score >= 20% within the first 2 weeks)
      observed in the active rTMS group compared to the sham group (57% vs. 29%,
      chi(2)=4.667, p=0.031). (2) There was no significant difference observed in
      responder rates (46% vs. 36%, chi(2)=0.295, p=0.586) or in remission rates (39%
      vs. 29%, chi(2)=0.319, p=0.572) between the two groups at 4 weeks. (3) There was
      a significant difference seen in both HAMD-17 and MADRS scores between the two
      groups at 2 and 4 weeks. The active rTMS group showed a significantly faster
      score reduction compared to the sham group at 2 weeks (HAMD-17, t=13.444,
      p=0.001; MADRS, t=30.123, p=0.000), which was maintained at 4 weeks on both
      scales (HAMD-17, t=46.915, p=0.000; MADRS, t=39.996, p=0.000). (4) The patients
      did not deteriorate in executive performance, and even improved in categories on
      WCST and completed TMT faster in the active group. CONCLUSIONS: RTMS accelerated
      the rapidity of the antidepressant response in first-episode young depressive
      patients. Our results call for future rTMS studies with larger sample sizes, high
      intensity of stimuli, and longer duration to draw more definitive conclusions.

PMID- 22391284
TI  - The impact of climate change on obsessive compulsive checking concerns.
AB  - OBJECTIVE: To investigate whether climate change has impacted on the nature of
      the obsessions or compulsions experienced by patients with obsessive compulsive
      disorder (OCD). METHODS: The sample comprised 50 patients with OCD checking
      subtype who had presented at the Anxiety Disorders Clinic at The University of
      Sydney seeking treatment during the period March 2008 to November 2009. Details
      of the type of obsessions and compulsions directly related to climate change
      phenomena were identified. RESULTS: Fourteen of the 50 participants (28%) were
      identified as having OCD concerns directly related to climate change. The most
      frequent concerns involved electricity, water and gas wastage. Less frequent
      concerns included pets dying of thirst and one participant was concerned about
      house damage due to floors cracking, pipes leaking; roof problems and white ant
      activity. Compulsions included checking and rechecking pet water bowls, light
      switches, taps, stoves, skirting boards, pipes, roofs and wooden structures.
      While these behaviours are not particularly unusual for people with this
      condition, it was the rationale they provided for carrying them out that was
      surprising. Instead of checking and rechecking so as to prevent fire or flood,
      the rituals were specifically performed so as to reduce their global footprint,
      or respond to climate change-induced negative events. CONCLUSIONS: Our findings
      demonstrate that the types of obsessions and compulsions experienced by 28% of
      our sample were directly aligned with the current issue of climate change and the
      perceived dangers associated with this phenomenon. To our knowledge this
      represents the first documentation of the significant impact of climate change on
      the nature of the concerns experienced by people with OCD checking subtype. We
      suggest that mental health professionals need to be aware of, and assess for the
      presence of such concerns.

PMID- 22391285
TI  - Reconsidering benzodiazepines in the treatment of panic disorder.

PMID- 22391286
TI  - Commentary on 'The role of alprazolam for the treatment of panic disorder in
      Australia'.

PMID- 22391287
TI  - Are we becoming obsessed about climate change?

PMID- 22391288
TI  - Commentary on 'Palliative models of care for later stages of mental disorder:
      maximising recovery, maintaining hope and building morale'.

PMID- 22391289
TI  - Re: Sanders et al. (2011) Differences in patients' perceptions of Schizophrenia
      between Maori and New Zealand Europeans.

PMID- 22391290
TI  - Quetiapine-related harms are on the rise.

PMID- 22391291
TI  - It's all atypical: can clozapine cause atypical neuroleptic malignant syndrome?

PMID- 22391292
TI  - Products containing synthetic cannabinoids and psychosis.

PMID- 22391293
TI  - Cerclage wiring in displaced associated anterior column and posterior hemi
      transverse acetabular fractures.
AB  - PURPOSE: The effects of cerclage wiring in the open reduction and internal
      fixation of displaced associated anterior column and posterior hemi-transverse
      acetabular fractures were evaluated. METHODS: This is a retrospectively clinical
      study of such cases where the main surgical strategy was open reduction and
      internal fixation with cerclage wire and reconstruction plates. Data on 12 cases
      treated between 1992 and 2011 were collected. The mean follow-up period was 32
      (12-132) months. RESULTS: Reduction with a fracture gap of less than 2 mm without
      articular stepping and solid union was achieved in all 12 cases. Postoperative
      complication developed in one case of symptomatic arthritis. Excluding the case
      with symptomatic arthritis, the other cases had good to excellent final D'Aubigne
      and Postel functional results. CONCLUSIONS: Cerclage wiring is very useful and
      effective in the reduction and fixation of displaced associated anterior column
      and posterior hemi-transverse acetabular fractures, and supplemental fixation
      with reconstruction plates and screws is necessary.

PMID- 22391294
TI  - The effectiveness of hypertonic saline and pentoxifylline (HTS-PTX) resuscitation
      in haemorrhagic shock and sepsis tissue injury: comparison with LR, HES, and LR
      PTX treatments.
AB  - PURPOSE: To compare lung and liver injury and laboratory results in haemorrhagic
      shock and sepsis models treated with combinations of lactated Ringer's solution
      (LR), 7.5% hypertonic saline (HTS), hydroxyethyl starch (HES), and pentoxifylline
      (PTX). METHODS: Male Sprague-Dawley rats (200-290 g) were assigned randomly to
      one of four treatment groups (n=16 per group): (1) LR; (2) HES; (3) LR-PTX; and
      (4) HTS-PTX. Each group was subdivided into (1) haemorrhagic shock (n=8) and (2)
      sepsis (n=8) model groups. A venous catheter was used to inject resuscitation
      fluids, and an arterial catheter was used to withdraw blood and monitor mean
      arterial pressure (MAP). Lung and liver histology, bronchoalveolar lavage (BAL)
      fluid, and cytokine levels were evaluated. RESULTS: The mean lung injury score
      was 1.7. At 24h after treatment, the total leucocyte count in the BAL fluid was
      significantly (p<0.05) higher with LR treatment (10 * 10(6) +/- 0.8) than with
      other treatments in the sepsis model groups (HES, 6 * 10(6) +/- 1.2; LR-PTX, 5 *
      10(6) +/- 1.5; HTS-PTX, 5 * 10(6) +/- 0.6). The higher total leucocyte count
      after LR treatment was attributable to a greater increase in the number of
      neutrophils (17 +/- 1.5%) compared with increases after the other treatments
      (HES, 6 +/- 0.8%; LR-PTX, 10 +/- 1.3%; HTS-PTX, 5 +/- 0.4%). In the sepsis model
      groups, the total hepatic injury score was also significantly (p<0.05) higher
      with LR treatment (9.9 +/- 0.5) than with the other treatments (HES, 6.7 +/- 0.8;
      LR-PTX, 5.6 +/- 0.7; HTS-PTX, 3.1 +/- 0.9). This also occurred in the shock model
      (LR, 10.6 +/- 2.1; HES, 5.8 +/- 0.9; LR-PTX, 7.3 +/- 0.9; HTS-PTX, 3.5 +/- 0.9).
      As compared with LR treatment, HTS-PTX resuscitation resulted in a 49% decrease
      in TNF-alpha, 29% decrease in IL-1beta, and 58% decrease in IL-6 in the shock
      model at 24h (p<0.05), and the respective decreases were 45, 24, and 35% in the
      sepsis model (p<0.05). CONCLUSION: HTS-PTX was superior to HES, LR-PTX, and LR
      for treating shock and sepsis, and LR-PTX and HES gave better results than LR
      therapy alone.

PMID- 22391295
TI  - Gene expression pattern of adiponectin and adiponectin receptors in dominant and
      atretic follicles and oocytes screened based on brilliant cresyl blue staining.
AB  - Adiponectin and its receptors (AdipoR1 and AdipoR2) are novel endocrine systems
      that act at various levels to control male and female fertility. The aim of this
      study was to determine whether adiponectin and its receptors gene expression
      levels differ between dominant follicle (DF) and atretic follicle (AF) and also
      between oocytes which were stained positively and negatively with brilliant
      cresyl blue (BCB(+) and BCB(-)). Based on estradiol/progesterone ratio, follicles
      from ovaries were classified as AFs and DFs. The stages of estrous cycle
      (follicular or luteal phases) were defined by macroscopic observation of the
      ovaries and the uterus. Oocytes were stained with BCB for 90 min. The relative
      expression of adiponectin, AdipoR1 and AdipoR2 mRNA in theca and cumulus cells
      and oocytes of different follicles were determined by quantitative real time PCR.
      Adiponectin and its receptors genes were clearly expressed higher (P<0.05) in
      theca and cumulus cells and oocytes of DFs than those of AFs during the
      follicular and luteal phases. BCB(+) oocytes showed a higher (P<0.05) expression
      of adiponectin and its receptors compared with their BCB(-) counterparts.
      Positive correlation (r>0.725, P<0.001) was observed between adiponectin mRNA
      level in ovarian cells of DFs and follicular fluid E2 concentration in follicular
      phase. Adiponectin mRNA abundance in ovarian cells of AFs showed a significant
      negative correlation with follicular fluid progesterone concentration in
      follicular and luteal phases (r<-0.731, P<0.001). This work has revealed the
      novel association of adiponectin and its receptors genes with follicular
      dominance and oocyte competence, thereby opening several new avenues of research
      into the mechanisms of dominance and competence in animal and human.

PMID- 22391296
TI  - Changes in pupil diameter entrained by cortically initiated changes in attention.
AB  - The diameter of the pupil is affected by changes in ambient illumination, color,
      spatial structure, movement, and mental effort. It has now been found that pupil
      diameter can be affected by cognitive processes. That is, it can be entrained by
      alternations between broadly spread and narrowly focused attention that are cued
      exogenously (attention is "summoned" by the cue) or endogenously (attention
      changes under the perceiver's intentional control). Pupil diameter also is
      affected by post-eye-blink constrictions that occur most often when attention is
      narrowed, and possibly by changes evoked by the near reflex, although changes in
      attention state parsimoniously account for the entirety of the results. Changes
      in pupil diameter produce differences in spherical aberration that alternately
      blur (when the pupil dilates) and sharpen the retinal image (when the pupil
      constricts), affecting the relative sensitivity of large receptive fields that
      mediate broadly spread attention compared with smaller receptive fields that
      mediate more narrowly focused attention. Results for endogenously cued,
      intentional changes in attentional spread provide definitive behavioral evidence
      for cortical feedback to subcortical nuclei that control pupil diameter, either
      directly or through pupil-constricting eye blinks. Analyses of convergent and
      divergent changes in eye position indicate that the near reflex was activated
      long after the initiation of relatively gradual attentionally cued changes in
      pupil diameter, and further, that when it occurs, the near reflex facilitates
      ongoing changes in pupil diameter.

PMID- 22391297
TI  - Hedgehog signaling.
AB  - The original hedgehog (hh) gene was found in Drosophila and named for the
      appearance of a mutant phenotype which causes an embryo to be covered with pointy
      denticles, thus resembling a hedgehog. The hedgehog family consists of sonic
      hedgehog (Shh), desert hedgehog (Dhh), and Indian hedgehog (Ihh). Shh is found in
      vertebrates and the best studied ligand of the hedgehog signaling pathway
      (Gilbert, 2000). It plays an important role in regulating vertebrate
      organogenesis, such as in the growth of digits on limbs and organization of the
      brain, and earlier studies also show that it is important during retinal
      development (for a review, see Amato et al., 2004). Hedgehog expression drives
      waves of neurogenesis in animal retina, although genetic programs that control
      its expression are poorly elucidated. Recently, a novel transcriptional cascade
      which involves the atonal and Iroquois gene family was proposed in the regulation
      of hedgehog waves during vertebrate retinal development (Choy et al., 2010). This
      chapter will focus on Shh by addressing its signaling mechanisms and roles in
      vertebrate eye development, as well as a novel finding in retinogenesis.

PMID- 22391298
TI  - Canonical and noncanonical Hedgehog/GLI signaling in hematological malignancies.
AB  - The highly conserved Hedgehog/GLI signaling pathway regulates multiple aspects of
      embryonic development and plays a decisive role in tissue homeostasis and the
      hematopoietic system by controlling cell fate decisions, stem cell self-renewal,
      and activation. Loss of negative control of Hedgehog signaling contributes to
      tumor pathogenesis and progression. In the classical view of canonical Hedgehog
      signaling, Hedgehog ligand binding to its receptor Patched culminates in the
      activation of the key pathway activator Smoothened, followed by activation of the
      GLI transcription factors. Its essential function and druggability render
      Smoothened well suited to therapeutic intervention. However, recent evidence
      suggests a critical role of Smoothened-independent regulation of GLI activity by
      several other signaling pathways including the PI3K/AKT and RAS/RAF/MEK/ERK axes.
      In addition, the contribution of canonical Hedgehog signaling via Patched and
      Smoothened to normal and malignant hematopoiesis has been the subject of recent
      controversies. In this review, we discuss the current understanding and
      controversial findings of canonical and noncanonical GLI activation in
      hematological malignancies in light of the current therapeutic strategies
      targeting the Hedgehog pathway.

PMID- 22391300
TI  - Gli protein nuclear localization signal.
AB  - Drosophila cubitus interruptus (Ci) and its vertebrate homologues, the
      glioblastoma (Gli) protein family, are the transcription factors belonging to the
      metazoan Gli/Glis/Zic ZF protein superfamily that shares similar five tandemly
      repeated C2H2-type zinc finger (ZF) motifs. Nuclear transport of Gli/Ci proteins
      is regulated by hedgehog (Hh) signaling and is an essential part of the Hh signal
      transduction pathway. Gli/Ci proteins possess a nuclear localization signal (NLS)
      and a nuclear export signal (NES), both of which are key signatures for
      controlling nucleocytoplasmic shuttling. The NLS of the Gli/Ci proteins has been
      mapped to the fifth ZF domain and its C-terminal side. It contains two clusters
      of basic residues (classical bipartite-type), which are conserved in metazoan
      Gli/Ci homologues, but which partially deviate from the intra-ZF domain NLSs in
      the Glis and Zic proteins. Recently, Importin alpha3 was identified as a nuclear
      transport protein for Ci. When we modeled the 3D structure of the Gli NLS
      Importin alpha complex, the two basic clusters were predicted to fit in the two
      binding interfaces of Importin alpha. The mechanisms controlling the function of
      NLSs and NESs involve the elimination of the NES by Hh signaling-dependent
      protein cleavage in the Ci and the Gli3 proteins, and the phosphorylation of a
      threonine residue close to the NLS in Gli1. Both processes depend on the activity
      of protein kinase A, which has a critical role in Hh signaling in fly wing discs.
      In addition, the Roadkill protein, a substrate recognition component of E3
      ubiquitin ligase, competes with the Ci protein to interact with Importin alpha3
      resulting in inhibition of Ci protein nuclear import.

PMID- 22391299
TI  - Noncanonical Hedgehog signaling.
AB  - The notion of noncanonical hedgehog (Hh) signaling in mammals has started to
      receive support from numerous observations. By noncanonical, we refer to all
      those cellular and tissue responses to any of the Hh isoforms that are
      independent of transcriptional changes mediated by the Gli family of
      transcription factors. In this chapter, we discuss the most recent findings that
      suggest that Patched1 can regulate cell proliferation and apoptosis independently
      of Smoothened (Smo) and Gli and the reports that Smo modulates actin cytoskeleton
      dependent processes such as fibroblast migration, endothelial cell tubulogenesis,
      axonal extension, and neurite formation by diverse mechanisms that exclude any
      involvement of Gli-dependent transcription. We also acknowledge the existence of
      less stronger evidence of noncanonical signaling in Drosophila.

PMID- 22391301
TI  - Mammalian homologues of Drosophila fused kinase.
AB  - Sonic Hedgehog (Shh) signaling pathway is implicated in various developmental and
      postnatal processes. Much of the current knowledge about the mechanisms of Shh
      signal transduction in vertebrates comes from the investigations of the
      respective pathway in fruit fly Drosophila melanogaster. In Drosophila,
      serine/threonine kinase fused is involved in all aspects of regulation of the Hh
      dependent transcription factor cubitus interruptus possessing both catalytic and
      regulatory functions. Two proteins, Stk36 and Ulk3, share similarity with fu and
      have been suggested as mammalian fu homologues. However, in vivo data clarify
      that Stk36 is not required for embryonic development in mice and participates in
      Shh-independent genesis of motile cilia. Even if Stk36 is associated with any
      pathological or physiological aspect of postnatal Shh signaling in mammals, it
      has perhaps only regulatory functions since its catalytic activity seems to be
      lost during evolution. In contrast to Stk36, Ulk3 is an active kinase. In non
      stimulated cells, Ulk3 catalytic activity is blocked, and it is involved in
      negative control of Gli proteins, mediators of Shh signaling. In response to Shh,
      Ulk3 positively regulates Gli proteins by directly phosphorylating them. Thus,
      Ulk3 is able to recapitulate both positive and negative roles of fu in vitro.
      However, Ulk3 functioning in vivo remains to be investigated.

PMID- 22391304
TI  - Sonic Hedgehog regulates Wnt activity during neural circuit formation.
AB  - Gradients of secreted morphogens, such as Sonic hedgehog (Shh), Wnt, and
      TGFbeta/Bmp, have classically been shown to control many aspects of early
      development by regulating cell proliferation and determining cell fate. However,
      recent studies demonstrate that these molecules also play important and
      evolutionarily conserved roles in later aspects of neural development. Depending
      on the context, these molecules can elicit gene transcription in the nucleus, or
      alternatively can provide instructive signals at the growth cone that induce
      local and rapid changes in cytoskeletal organization. Shh can activate different
      cellular transduction pathways via its binding to alternative coreceptor
      complexes or simply by adaptation of its "classical" signaling pathway. However,
      in most of its activities during neural development, Shh does not act alone but
      rather in concert with other morphogens, particularly the Wnts. This review
      provides an overview of the mechanisms by which Shh signaling acts in concert
      with Wnts to mediate a myriad of cellular processes that are required for neural
      circuit formation.

PMID- 22391302
TI  - Identification, functional characterization, and pathobiological significance of
      GLI1 isoforms in human cancers.
AB  - Glioma-associated oncogene homolog 1 (GLI1) is the nuclear mediator of Hedgehog
      signaling that activates gene transcription via its zinc finger DNA-binding and
      transactivation domains. GLI1 plays a critical role in several cellular
      processes, including embryonic development, tumorigenesis, and tumor growth and
      progression. The human GLI1 gene was identified in 1987 as an amplified gene in
      glioblastoma. Somatic mutations have never been reported in the GLI1 gene in any
      cell or tumor type. Very recently in 2008-2009, the full-length GLI1 transcript
      was discovered to undergo alternative splicing to form two shorter isoforms,
      namely N-terminal deletion variant (GLI1DeltaN) and truncated GLI1 (tGLI1).
      Emerging evidence suggests that the three structurally different GLI1 isoforms
      are distinctly different in their expression patterns and functions in the
      context of human cancers. The tGLI1 isoform, in particular, has been shown to
      gain the ability to modulate expression of the genes that are not regulated by
      GLI1 and to support the biology of more aggressive cancer. Consequently, a key
      focus of this chapter is to summarize and compare the properties of the three
      GLI1 isoforms and their relations to malignant biology of human cancers.

PMID- 22391305
TI  - Hedgehog/Gli control by ubiquitination/acetylation interplay.
AB  - Hedgehog is a key morphogen regulating development and leading to tumorigenesis,
      when hyperactivated. Hedgehog signaling is mediated by transcriptional effectors
      belonging to the Gli family. Ubiquitination-related posttranslational
      modifications of the Gli transcription factors, leading to proteasome-dependent
      proteolytic cleavage or massive degradation, represent an important mechanism of
      regulation of the pathway. Gli ubiquitination is controlled by a number of E3
      ligases belonging to the RING/Cullin and HECT families. These E3 ligases are
      regulated by several members of the Hh pathway itself (e.g., Smo-activated
      kinases) as well as by proteins belonging to other signaling cascades (i.e., Numb
      activated Itch). These proteolytic signals finally suppress Gli function either
      directly or indirectly (i.e., suppression of HDAC1-mediated Gli deacetylation).
      The complex of these regulatory circuitries finely tunes Hedgehog signaling
      providing a tight control of developmental processes, the subversion of which
      leads to tumorigenesis. To this regard, these ubiquitination processes represent
      promising targets for novel therapeutic strategies.

PMID- 22391303
TI  - Gli-similar proteins: their mechanisms of action, physiological functions, and
      roles in disease.
AB  - Gli-similar (Glis) 1-3 proteins constitute a subfamily of Kruppel-like zinc
      finger proteins that are closely related to members of the Gli family. Glis
      proteins have been implicated in several pathologies, including cystic kidney
      disease, diabetes, hypothyroidism, fibrosis, osteoporosis, psoriasis, and cancer.
      In humans, a mutation in the Glis2 gene has been linked to the development of
      nephronophthisis (NPHP), a recessive cystic kidney disease, while mutations in
      Glis3 lead to an extended multisystem phenotype that includes the development of
      neonatal diabetes, polycystic kidneys, congenital hypothyroidism, and facial
      dysmorphism. Glis3 has also been identified as a risk locus for type-1 and type-2
      diabetes and additional studies have revealed a role for Glis3 in pancreatic
      endocrine development, beta-cell maintenance, and insulin regulation. Similar to
      Gli1-3, Glis2 and 3 have been reported to localize to the primary cilium. These
      studies appear to suggest that Glis proteins are part of a primary cilium
      associated signaling pathway(s). It has been hypothesized that Glis proteins are
      activated through posttranslational modifications and subsequently translocate to
      the nucleus where they regulate transcription by interacting with Glis-binding
      sites in the promoter regions of target genes. This chapter summarizes the
      current state of knowledge regarding mechanisms of action of the Glis family of
      proteins, their physiological functions, as well as their roles in disease.

PMID- 22391307
TI  - Phosphorylation regulation of Hedgehog signaling.
AB  - The study of posttranslational regulation of proteins has occupied biochemists
      for well over a half century. Understanding balanced phosphorylation and
      dephosphorylation of the proteins may be the key to meeting some of the most
      pressing scientific challenges. A detailed examination of the phosphorylation of
      many components in the Hedgehog (Hh) pathway leads to a better understanding of
      the Hh signaling mechanisms. This chapter describes the precise phosphorylation
      that evolves during the phosphorylation/dephosphorylation of players in the Hh
      signaling cascade, including the signal transducer Smoothened and the
      transcription factor Ci/Gli.

PMID- 22391306
TI  - Palmitoylation of Hedgehog proteins.
AB  - Hedgehog (Hh) proteins are secreted signaling proteins that contain amide-linked
      palmitate at the N-terminus and cholesterol at the C-terminus. Palmitoylation of
      Hh proteins is critical for effective long- and short-range signaling. The
      palmitoylation reaction occurs during transit of Hh through the secretory
      pathway, most likely in the lumen of the ER. Attachment of palmitate to Hh
      proteins is independent of cholesterol modification and autoprocessing and is
      catalyzed by Hhat (Hedgehog acyltransferase). Hhat is a member of the membrane
      bound O-acyltransferase (MBOAT) family, a subgroup of multipass membrane proteins
      that catalyze transfer of fatty acyl groups to lipids and proteins. Several
      classes of secreted proteins have recently been shown to be substrates for MBOAT
      acyltransferases, including Hh proteins and Spitz (palmitoylated by Hhat), Wg/Wnt
      proteins (modified with palmitate and/or palmitoleate by Porcupine) and ghrelin
      (octanoylated by ghrelin O-acyltransferase). These findings highlight protein
      fatty acylation as a mechanism that not only influences membrane binding of
      intracellular proteins but also regulates the signaling range and efficacy of
      secreted proteins.

PMID- 22391308
TI  - Protein kinase A activity and Hedgehog signaling pathway.
AB  - Protein kinase A (PKA) is a well-known kinase that plays fundamental roles in a
      variety of biological processes. In Hedgehog-responsive cells, PKA plays key
      roles in proliferation and fate specification by modulating the transduction of
      Hedgehog signaling. In the absence of Hedgehog, a basal level of PKA activity
      represses the transcription of Hedgehog target genes. The main substrates of PKA
      in this process are the Ci/Gli family of bipotential transcription factors, which
      activate and repress Hedgehog target gene expression. PKA phosphorylates Ci/Gli,
      promoting the production of the repressor forms of Ci/Gli and thus repressing
      Hedgehog target gene expression. In contrast, the activation of Hedgehog
      signaling in response to Hedgehog increases the active forms of Ci/Gli, resulting
      in Hedgehog target gene expression. Because both decreased and increased levels
      of PKA activity cause abnormal cell proliferation and alter cell fate
      specification, the basal level of PKA activity in Hedgehog-responsive cells
      should be precisely regulated. However, the mechanism by which PKA activity is
      regulated remains obscure and appears to vary between cell types, tissues, and
      organisms. To date, two mechanisms have been proposed. One is a classical
      mechanism in which PKA activity is regulated by a small second messenger, cAMP;
      the other is a novel mechanism in which PKA activity is regulated by a protein,
      Misty somites.

PMID- 22391309
TI  - Phosphorylation of Gli by cAMP-dependent protein kinase.
AB  - Hedgehog (Hh) signaling plays a central role in many developmental processes. Hh
      protein is a developmental morphogen that elicits a graded cellular response
      depending on the distance between the recipient cell and the ligand-secreting
      cell. Gli transcription factors are effectors that induce the expression of
      downstream target genes. The outline of this cascade from Hh to Gli has been
      elucidated, and many components have been identified. However, the interpretation
      of graded ligand stimulation remains to be resolved. Among the components,
      adenosine 3'5'-cyclic monophosphate-dependent protein kinase (PKA) functions as a
      negative regulator that phosphorylates a specific region of Gli, thereby inducing
      proteolytic cleavage to generate the repressor form. In addition, recent studies
      have identified different mechanisms that are followed by PKA phosphorylation of
      Gli. In this review, we examine Hh signaling and PKA phosphorylation and propose
      a possible interaction between the multiple mechanisms regulated by PKA and the
      gradient-dependent response.

PMID- 22391310
TI  - ZFP932 suppresses cellular Hedgehog response and Patched1 transcription.
AB  - Substantial amount of research has been devoted to the understanding of hedgehog
      (Hh) signal transduction in the past two decades. Although significant progresses
      have been made on the understanding of individual signaling components of this
      pathway, the transcriptional regulation of these components is not as well
      understood. We have recently characterized a novel Kruppel-associated box (KRAB)
      domain containing zinc finger transcription factor ZFP932 (formerly known as
      ZNF431) and showed that it transcriptionally regulates several components of the
      Hh pathway. ZFP932 is part of the largest KRAB-domain zinc finger transcription
      factor family in the mammalian genome. However, the in vivo functions for the
      majority of these transcription factors as well as their downstream targets are
      not fully understood. ZFP932 is a nuclear KRAB-domain zinc finger transcriptional
      repressor that recruits HDACs to target promoters. Using the embryonic limb
      mesenchymal cell line MPLB, we uncovered many potential targets for ZFP932. Among
      them, Patched1 (Ptch1) was found to be a direct transcriptional target of ZFP932.
      Promoter analyses using reporter assays as well as electrophoretic mobility shift
      assays revealed three ZFP932 binding sites in the Ptch1 proximal promoter which
      are bound by ZFP932 in vivo as demonstrated by chromatin immunoprecipitation.
      Consistently, overexpression of ZFP932 either in MPLB cells or in Xenopus and
      mouse embryos strongly repressed Ptch1 expression. Conversely, shRNA knockdown of
      Zfp932 in MPLB cells elevated Ptch1 expression. In addition to regulating Ptch1
      transcription, we demonstrated that ZFP932 also regulates hedgehog signaling as
      Hh pathway readouts are reduced in ZFP932 overexpression and elevated in ZFP932
      knockdown MPLB cells. Moreover, perturbation of ZFP932 expression in C3H10T1/2
      cells affected Hh-induced osteoblast differentiation. Together, these results
      implicate ZFP932 in Hh signaling by transcriptionally regulating Hh signal
      component expression.

PMID- 22391311
TI  - A new era for an ancient drug: arsenic trioxide and Hedgehog signaling.
AB  - Arsenic has been used for ages as a therapeutic agent. Currently, it is an FDA
      approved drug to treat acute promyelocytic leukemia where it leads to degradation
      of the PML-RAR fusion protein. It has been shown to have various other targets in
      cells such as JNK, NFkappaB, thioredoxin reductase, and MAPK pathways. Most of
      its effects in cells have been through arsenic's ability to bind to thiol groups
      in cysteine residues. Recent evidence has shown that arsenic can inhibit the
      Hedgehog pathway by inhibiting GLI proteins. The proposed mechanism of action is
      through direct binding. Potential binding sites include the critical cysteine
      residues in GLI zinc finger domains. The role of the Hedgehog pathway has been
      implicated in many cancers such as basal cell carcinoma, medulloblastoma, Ewing
      sarcoma, and rhabdoid tumors. Current Hedgehog pathway inhibitors have been
      fraught with resistance issues and so arsenic trioxide may provide an alternative
      therapy when combined with these other inhibitors or after acquired resistance.

PMID- 22391312
TI  - Aberrations and therapeutics involving the developmental pathway Hedgehog in
      pancreatic cancer.
AB  - To conduct a systematic review of the role that the hedgehog signaling pathway
      has in pancreatic cancer tumorigenesis. A PubMed search from 2000 to 2010 and
      literature-based references were sourced. It was found that in 2009 a genetic
      analysis of pancreatic cancers discovered that a core set of 12 cellular
      signaling pathways including hedgehog were genetically altered in 67-100% of
      cases. Second, in vitro and in vivo studies of treatment with cyclopamine (a
      naturally occurring antagonist of the hedgehog signaling pathway component;
      Smoothened) have shown that inhibition of hedgehog can abrogate pancreatic cancer
      metastasis. Third, experimental evidence has demonstrated that sonic hedgehog
      (Shh) is correlated with desmoplasia in pancreatic cancer. This is important
      because targeting the Shh pathway potentially may facilitate chemotherapeutic
      drug delivery as pancreatic cancers tend to have a dense fibrotic stroma that
      extrinsically compressed the tumor vasculature leading to a hypoperfusing
      intratumoral circulation. It is probable that patients with locally advanced
      pancreatic cancer will derive the greatest benefit from treatment with Smoothened
      antagonists. Fourth, it has been found that ligand-dependent activation by
      hedgehog occurs in the tumor stromal microenvironment in pancreatic cancer, a
      paracrine effect on tumorigenesis. Finally, in pancreatic cancer, cells with the
      CD44+CD24+ESA+ immunophenotype select a population enriched for cancer initiating
      stem cells. Shh is increased 46-fold in CD44+CD24+ESA+ cells compared with normal
      pancreatic epithelial cells. Medications that destruct pancreatic cancer
      initiating stem cells are a potentially novel strategy in cancer treatment. In
      conclusion, aberrant hedgehog signaling occurs in pancreatic cancer tumorigenesis
      and therapeutics that target the transmembrane receptor Smoothened abrogate
      hedgehog signaling and may improve the outcomes of patients with pancreatic
      cancer.

PMID- 22391313
TI  - Sonic Hedgehog signaling and potential therapeutic indications.
AB  - Sonic hedgehog (Shh) is a glycoprotein molecule that is expressed throughout the
      central nervous system (CNS). It is important during neurodevelopment,
      particularly through its induction of endogenous neural precursor cells and
      neural stem cells. The signaling system by which Shh has its diffuse effects on
      multiple end organs depends on a downstream signaling cascade initiated by
      binding to the receptor Patched (PTC) on Shh-specific target cells. The
      downstream signaling cascade has widespread effects on multiple organ systems.
      Research into tumor suppressive effects and germline mutations has uncovered
      important implications in neuro-oncology. Modulating the neuroproliferative
      effects of the Shh signaling cascade implicated a potential role in ameliorating
      the effects of CNS injury, particularly in animal models of spinal cord injury
      and cerebral cortical ischemia. This chapter provides a summary of the Shh
      signaling mechanism and a review of its impact in these neurological disorders.

PMID- 22391314
TI  - Sonic Hedgehog on microparticles and neovascularization.
AB  - Neovascularization represents a pivotal process consisting in the development of
      vascular network during embryogenesis and adult life. Postnatally, it arises
      mainly through angiogenesis, which has physiological and pathological roles in
      health and disease. Blood vessel formation results as tightly regulated multistep
      process which needs coordination and precise regulation of the balance of
      proangiogenic and antiangiogenic factors. Sonic Hedgehog (SHH), a morphogen
      belonging to Hedgehog (HH) family proteins, is implicated in a remarkably wide
      variety of process, including vessel development. Recent evidence demonstrate
      that, in addition to the classic factors, microvesicles (MVs), both
      microparticles (MPs) and exosomes, small vesicles released distinct cellular
      compartments, are involved in modulation of neovascularization. MPs generated
      from T lymphocytes undergoing both activation and apoptosis harbor at their
      surface SHH and play a crucial role in modulation of neovascularization. They are
      able to modulate the different steps implicated in angiogenesis process in vitro
      and to enhance postischemic neovascularization in vivo. As the consequence, we
      suggest that the MPs carrying SHH contribute to generation of a vascular network
      and may represent a new therapeutic approach to treat pathologies associated with
      failed angiogenesis.

PMID- 22391315
TI  - "Patch"-ing up the neurons: revival or enervation?
AB  - Since its identification Patched1 (Ptch1) has gained importance for playing a
      cardinal role in developmental patterning through Hedgehog (Hh) pathway, acting
      as a transmembrane receptor. Involvement of this protein in diverse aspects of
      the neuronal system, from development to regeneration and protection, including
      uncontrolled proliferation in oncogenic perspectives, makes it an intriguing
      candidate for investigation in neurobiology. Stem cell population of adult
      nervous system is also found to be regulated by Ptch1. Though not elaborately
      studied, research in this field for the past one decade has suggested a new
      spectrum of Ptch1 function through an alternative route independent of Hh. In
      this chapter, the available knowledge about Ptch1 in neuronal system is
      critically reviewed and further functional insights about this protein are
      evaluated.

PMID- 22391316
TI  - Activation of Hedgehog pathway in gastrointestinal cancers.
AB  - The hedgehog (Hh) pathway is a major regulator for cell differentiation, tissue
      polarity, and cell proliferation in embryonic development and homeostasis in
      adult tissue. Studies from many laboratories reveal activation of this pathway in
      a variety of human cancer, including basal cell carcinomas (BCCs),
      medulloblastomas, leukemia, gastrointestinal, lung, ovarian, breast, and prostate
      cancers. It is thus believed that targeted inhibition of Hh signaling may be
      effective in treatment and prevention of human cancer. Even more exciting is the
      discovery and synthesis of specific signaling antagonists for the Hh pathway,
      which have significant clinical implications in novel cancer therapeutics. In
      this review, we summarize major advances in the past 2 years in our understanding
      of Hh signaling activation in human gastrointestinal cancer and their potential
      in clinical treatment with Hh pathway inhibitors.

PMID- 22391318
TI  - Sonic Hedgehog-mediated synergistic effects guiding angiogenesis and
      osteogenesis.
AB  - Sonic hedgehog (Shh) is a morphogen controlling the skeletal and vascular
      development in the embryo but is also reactivated during adult repair processes.
      Thus, this molecule holds great therapeutic potential for biotechnological and
      biomedical approaches aiming to enhance tissue regeneration or to replace damaged
      tissues. According to present knowledge, Shh signaling controls the expression of
      several families of growth factors involved in neovascularization and vessel
      maturation and acts upstream of the most prominent angiogenic growth factor,
      vascular endothelial growth factor. In this context, a very interesting feature
      of Shh is that it controls both angiogenic activity and vessel stabilization by
      mural cells. In parallel, Shh seems to have a direct effect on endothelial cell
      tube formation and seems to trigger the differentiation process of mesenchymal
      stem cells toward the osteogenic lineage. In this chapter, we will therefore
      shortly summarize the multifaceted potential of Shh for bone repair and
      vascularization according to the current literature. In addition, we will show
      how coculture models based on outgrowth endothelial cells and primary osteoblasts
      can be used to reveal some of the relevant mechanisms by which Shh drives and
      connects bone regeneration and vascularization.

PMID- 22391317
TI  - The role of Sonic Hedgehog as a regulator of gastric function and
      differentiation.
AB  - The Hedgehog (Hh) genes play a key role in the regulation of embryonic
      development and govern processes such as cell differentiation, cell
      proliferation, and tissue patterning. In vertebrate embryos, Hh gene expression
      regulates correct formation of limbs, skeleton, muscles, and organs including
      stomach. In the adult, the Hh pathway functions in tissue repair and
      regeneration, along with maintenance of stem cells. Sonic Hedgehog (Shh)
      signaling has been extensively studied for its role in developmental and cancer
      biology. Recent advances in the field of gastroenterology show that in the
      stomach, Shh is responsible for proper differentiation of the gastric glands. The
      aberrant activity of the Shh signaling pathway leads to an altered gastric
      differentiation program and loss of gastric acid secretion that is the
      predominant function of the stomach. In this chapter, we review the most recent
      findings that reveal the role of Shh as a regulator of gastric function and
      differentiation and how this signaling is dysregulated during the development of
      gastric cancer in response bacterial infection.

PMID- 22391319
TI  - Hedgehog inhibition as an anti-cancer strategy.
AB  - Dysregulated Hedgehog (Hh) signaling has been implicated in a growing number of
      human cancers. Although first identified as an important developmental signaling
      pathway crucial for cellular proliferation, differentiation, and migration during
      organogenesis in invertebrates, these fundamental processes have been co-opted in
      human cancers. Initial evidence for the Hh pathway in tumor biology comes from
      mutations of signaling pathway components in a hereditary cancer syndrome that
      typically results in basal-cell carcinoma and medulloblastoma. Subsequent
      analysis revealed that Hh pathway mutations are found in sporadic tumors as well
      as activated Hh signaling in several epithelial cancers independent of Hh pathway
      mutation status. Further, recent evidence has demonstrated paracrine Hh signaling
      within stromal cells of the tumor microenvironment with implications for drug
      delivery. Several Hh antagonists targeting the Hh receptor, Smoothened (SMO),
      have been developed and show efficacy in preclinical studies and early-stage
      clinical trials in humans. However, major issues with these small molecule
      compounds include rapid acquired resistance, potential developmental toxicities
      secondary to use in children, and limited efficacy in cancers driven by Hh
      signaling downstream of the SMO receptor.

PMID- 22391320
TI  - Hedgehog signaling. Preface.

PMID- 22391321
TI  - Effect of calcium ions on the evolution of biofouling by Bacillus subtilis in
      plate heat exchangers simulating the heat pump system used with treated sewage in
      the 2008 Olympic Village.
AB  - Heat pump systems using treated sewage water as the heat source were used in the
      Beijing Olympic Village for domestic heating and cooling. However, considerable
      biofouling occurred in the plate heat exchangers used in the heat pump system,
      greatly limiting the system efficiency. This study investigates the biofouling
      characteristics using a plate heat exchanger in parallel with a flow cell system
      to focus on the effect of calcium ions on the biofilm development. The
      interactions between the microorganisms and Ca(2+) enhances both the extent and
      the rate of biofilm development with increasing Ca(2+) concentration, leading to
      increased heat transfer and flow resistances. Three stages of biofouling
      development were identified in the presence of Ca(2+) from different biofouling
      mass growth rates with an initial stage, a rapid growth stage and an extended
      growth stage. Each growth stage had different biofouling morphologies influenced
      by the Ca(2+) concentration. The effects of Ca(2+) on the biofouling heat
      transfer and flow resistances had a synergistic effect related to both the
      biofouling mass and the morphology. The effect of Ca(2+) on the biofouling
      development was most prominent during the rapid growth stage.

PMID- 22391322
TI  - Continuous monitoring of phospholipid vesicle hydrolysis by phospholipase D (PLD)
      reveals differences in hydrolysis by PLDs from 2 Streptomyces species.
AB  - Phospholipase D (PLD)-mediated hydrolysis of phosphatidylcholine (PC) in large
      unilamellar vesicles (LUVs) consisting of PC and either glycerol monooleate (GMO)
      or methyl oleate (MeO) were monitored in situ and in real time by using a choline
      oxidase-immobilized oxygen electrode. This technique revealed reaction
      differences between 2 bacterial PLDs. PLD from Streptomyces chromofuscus, which
      is closely homologous to bacterial alkaline phosphatase, hydrolyzed only 6% of
      surface PC owing to product inhibition. The catalytic activity of this enzyme was
      not sensitive to the addition of GMO. On the other hand, typical bacterial PLD
      from Streptomyces sp. was found to hydrolyze all the PC molecules at the outer
      surface of LUVs suggesting that this enzyme is free from product inhibition.
      Introduction of GMO or MeO into the bilayer increased exposure of the PC
      headgroup and facilitated PC hydrolysis mediated by PLD from Streptomyces sp. GMO
      and MeO have the same lipophilic tail but the latter lacks hydroxyl groups on its
      polar head. From kinetic analysis by using the Michaelis-Menten model extended to
      the reaction at the interface, these compounds were found to activate PLD from
      Streptomyces sp. in different ways, i.e., MeO increased the protein binding to
      membranes and GMO stimulated the enzyme-substrate complex formation at membrane
      surface.

PMID- 22391323
TI  - Trichostatin A induces cell death at the concentration recommended to
      differentiate the RGC-5 cell line.
AB  - Supplementation with Trichostatin A (TSA) has been described as the method of
      choice for differentiating the RGC-5 cell line into cells with neuronal
      properties. However, TSA is known to induce apoptosis. We therefore investigated
      whether TSA at the recommended concentration for differentiation (500 nM) and at
      three additional concentrations (40, 150 and 2000 nM) induces apoptosis or cell
      death in the RGC-5 cell line. Morphological changes of the RGC-5 cells occurred
      after 24 and 48 hours (h) of treatment with 500 and 2000 nM TSA. Differentiation
      of RGC-5 cell began at 150 nM. A decrease in the cell count was observed from 150
      nM TSA onwards compared to controls. Five hundred nanomolar of TSA reduced the
      amount of cells to 51% (p<0.005) after 24h and to 24% (p<0.005) after 48 h
      compared to controls on crystal violet staining. At 500 nM TSA a massive
      induction of apoptosis after 24 and 48 h was noted. Supplementation of 500 nM TSA
      increased caspase 3/7 activity 5.0-fold (p<0.005). Furthermore, 27* more TUNEL
      positive cells were found and the cleaved caspase 3/caspase 3 ratio was 1.8-fold
      (p<0.1) higher 24h after the addition of 500 nM TSA. The Bax/Bcl-2 ratio was 3.4
      fold (p<0.05) higher after 48 h. Cell viability decreased to 70% (p<0.005) and to
      35% (p<0.005) after 24 and 48 h, respectively. Moreover, 103* (p<0.05) more dead
      cells (via propidium iodide staining) were found after 48 h of treatment with 500
      nM TSA. In conclusion, TSA induces cell death and apoptosis at the concentration
      recommended for differentiation. The induction of apoptosis occurred dose and
      time dependently and already at even lower concentrations of TSA which did not
      lead to differentiation induced apoptosis. Thus, studies with RGC-5 cells should
      not be performed within the first 48 h after supplementation with TSA.

PMID- 22391324
TI  - Chronic inhibition of nitric oxide synthase activity by NG-nitro-L-arginine
      induces nitric oxide synthase expression in the developing rat cerebellum.
AB  - Studies on chronic inhibition of nitric oxide synthase (NOS) in the CNS suggest a
      plastic change in nitric oxide (NO) synthesis in areas related to motor control,
      which might protect the animal from the functional and behavioral consequences of
      NO deficiency. In the present study, the acute and chronic effect of the
      substrate analogue inhibitor N(G)-nitro-l-arginine (l-NNA) was examined on NO
      production, NO-sensitive cyclic guanosine monophosphate (cGMP) levels and the
      expression of NOS isoforms in the developing rat cerebellum. Acute
      intraperitoneal administration of the inhibitor (5-200mg/kg) to 21-day-old rats
      reduced NOS activity and NO concentration dose dependently by 70-90% and the
      tissue cGMP level by 60-80%. By contrast, chronic application of l-NNA between
      postnatal days 4-21 diminished the total NOS activity and NO concentration only
      by 30%, and the tissue cGMP level by 10-50%. Chronic treatment of 10mg/kg l-NNA
      induced neuronal (n)NOS expression in granule cells, as revealed by in situ
      hybridization, NADPH-diaphorase histochemistry and Western-blot, but it had no
      significant influence on tissue cGMP level or on layer formation of the
      cerebellum. However, a higher concentration (50mg/kg) of l-NNA decreased the
      intensity of the NADPH-diaphorase reaction in granule cells, significantly
      reduced cGMP production, and retarded layer formation and induced inducible
      (i)NOS expression & activity in glial cells. Treatments did not affect
      endothelial (e)NOS expression. The administration of the biologically inactive
      isomer D-NNA (50mg/kg) or saline was ineffective. The present findings suggest
      the existence of a concentration-dependent compensatory mechanism against
      experimentally-induced cronich inhibition of NOS, including nNOS or iNOS up
      regulation, which might maintain a steady-state NO level in the developing
      cerebellum.

PMID- 22391325
TI  - Function and regulation of taurine transport in Muller cells under osmotic
      stress.
AB  - In the retina, taurine works as an osmolyte to exert a neuroprotective function,
      and it has been proposed that Muller cells, a major type of retinal glial cells,
      are involved in the osmolarity regulation of retinal neural cells by controlling
      the taurine concentration in retinal extracellular fluid (ECF). However, the
      detailed mechanism of taurine transport in Muller cells has not fully examined,
      and we investigated this using a conditionally immortalized rat Muller cell line
      (TR-MUL5 cells). In the uptake study, TR-MUL5 cells exhibited Na(+)-, Cl(-)
      dependent [(3)H]taurine uptake with a K(m) of 37.9MUM. The [(3)H]taurine uptake
      by TR-MUL5 cells was strongly inhibited by beta-alanine and hypotaurine,
      substrates of taurine transporter TAUT (SLC6A6), and RT-PCR and immunoblot
      analyses demonstrated the expression of TAUT in Muller cells, suggesting the
      involvement of TAUT in taurine uptake by Muller cells. In the efflux study,
      [(3)H]taurine efflux by TR-MUL5 cells under hypotonic conditions was
      significantly greater than that under isotonic conditions, and significantly
      enhanced by sphingosine 1-phosphate (S1P), suggesting that the volume-sensitive
      taurine release is enhanced via G protein-coupled receptors (GPCRs) in Muller
      cells. Furthermore, [(3)H]taurine efflux by TR-MUL5 cells under hypotonic
      conditions was significantly inhibited in the presence of the volume-sensitive
      organic osmolyte and anion channel (VSOAC) inhibitor, suggesting a major
      contribution of VSOAC to the volume-sensitive taurine release by Muller cells.
      This is the first description of the detailed mechanism of taurine transport in
      Muller cells, indicating a possible function of Muller cells in retinal
      neuroprotection by regulating osmolarity of retinal ECF.

PMID- 22391326
TI  - Hydrogen sulfide producing enzymes in pregnancy and preeclampsia.
AB  - Preeclampsia, a human pregnancy specific disorder is characterized by an anti
      angiogenic state. As hydrogen sulfide (H(2)S) has pro-angiogenic and anti
      oxidative characteristics, we hypothesized that H(2)S levels could play a role in
      the pathogenesis of preeclampsia and studied the placental expression of the
      H(2)S-producing enzymes cystathionine-gamma-lyase (CSE) and cystathionine-beta
      synthase (CBS). CBS and CSE protein are expressed in the fetal-placental
      endothelium and CBS only in Hofbauer cells. CBS mRNA expression is decreased (p =
      0.002) in early-onset preeclampsia, while CSE mRNA is unchanged. Thus, down
      regulation of CBS during early-onset preeclampsia may result in less H(2)S
      production and may aid in the anti-angiogenic state.

PMID- 22391327
TI  - Role of arginase-2 and eNOS in the differential vascular reactivity and hypoxia
      induced endothelial response in umbilical arteries and veins.
AB  - The main vasodilator in the placenta is nitric oxide (NO), which is synthesized
      by endothelial NO synthase (eNOS). Arginase-2 competes with eNOS for l-arginine,
      and its activity has been related with vascular dysfunction. Recently, we showed
      that hypoxia induces arginase-2, and decreases eNOS activity in human umbilical
      vein endothelial cells (HUVEC). However there is evidence that vascular responses
      to hypoxia are not similar throughout the placental vascular tree. We studied
      whether arginase-2 plays a role controlling vascular tone in human umbilical
      vessels, and the changes in the expression of arginase-2 and eNOS proteins by
      hypoxia in endothelial cells from umbilical arteries (HUAEC) and veins (HUVEC).
      In isolated umbilical vessels the presence of eNOS and arginase-2 was determined
      in the endothelium, and the NO-dependent vasoactive responses in the presence and
      absence of S-(2-boronoethyl)-L-cysteine (BEC, arginase inhibitor) were studied.
      Additionally, HUAEC and HUVEC were exposed (0-24 h) to hypoxia (2% O2) or
      normoxia (5% O2), and protein levels of eNOS (total and phosphorylated at serine
      1177) and arginase-2 were determined. In umbilical arteries and veins arginase-2
      and eNOS were detected mainly at the endothelium. BEC induced a higher
      concentration-dependent relaxation in umbilical arteries than veins, and these
      responses were NOS-dependent. In HUAEC exposed to hypoxia there were no changes
      in eNOS and arginase-2 levels, however there was a significant increase of p
      eNOS. In contrast, HUVEC showed an increase in arginase-2 and a reduction of p
      eNOS in response to hypoxia. These results show that arginases have a vascular
      role in placental vessels counteracting the NOS-dependent relaxation, which is
      differentially regulated in placental artery and vein endothelial cells.

PMID- 22391328
TI  - [Formation and quantification assay of Candida albicans and Staphylococcus aureus
      mixed biofilm].
AB  - This study quantifies the production of single and mixed biofilms of Candida
      albicans and Staphylococcus aureus to determine if such mixed biofilms have
      synergistic effects. Assays were performed using polystyrene microtitre plates of
      96 wells, metabolic activity was measured by the enzymatic reduction of a
      tetrazolium salt (XTT) and colorimetric changes were measured at 490 nm. Confocal
      scanning laser microscopy was used to visualise the biofilms of each
      microorganism and its growth kinetics. The highest levels of biofilm formation
      were observed in mixed biofilms, followed by those of Candida albicans only, with
      the lowest levels of biofilm formation being detected for Staphylococcus aureus;
      all together these results suggest a synergistic relationship between the tested
      microorganisms.

PMID- 22391329
TI  - Separation of nucleobases and their derivatives with organic-high ionic strength
      aqueous phase systems by spiral high-speed counter-current chromatography.
AB  - A set of nucleic acid constituents were separated with ultra polar two-phase
      solvent systems by a spiral multilayer coil mounted on the rotary frame of a type
      J coil planet centrifuge. These two-phase systems were composed of 1
      butanol/ethanol/50% saturated aqueous ammonium sulfate at various volume ratios.
      Nucleobases including adenine, cytosine, uracil, and thymine; nucleosides
      including adenosine, guanosine, cytidine, and uridine; and nucleotides including,
      AMP, GMP, CMP, UMP, and TMP are partitioned in each group with suitable solvent
      ratios. Adenine derivatives such as adenosine, AMP, ADP, and ATP were well
      resolved in the most polar solvent system composed of ethanol/50% saturated
      aqueous ammonium sulfate at a volume ratio of 1:2. It was found that cytosine and
      cytidine peaks showed some irregular two peaks probably due to their keto and
      enol isomers, while the separation of AMP forms two peaks especially when TMP was
      added in the sample solution, the mechanism of which is now under investigation
      in our laboratory.

PMID- 22391330
TI  - Gas chromatography-mass spectrometry determination of pharmacologically active
      substances in urine and blood samples by use of a continuous solid-phase
      extraction system and microwave-assisted derivatization.
AB  - A sensitive method based on gas chromatography-mass spectrometry was used to
      determine 22 pharmacologically active substances (frequently used in the
      treatment of human and animal's diseases) including analgesics, antibacterials,
      anti-epileptics, antiseptics, beta-blockers, hormones, lipid regulators and non
      steroidal anti-inflammatories in blood and urine samples. Samples were subjected
      to continuous solid-phase extraction in a sorbent column (Oasis HLB), and then
      the target analytes were eluted with ethyl acetate and derivatized in a household
      microwave oven at 350 W for 3 min. Finally, these products were determined in a
      gas chromatograph-mass spectrometer equipped with a DB-5 fused silica capillary
      column. The analyte detection limits thus obtained ranged from 0.2 to 1.3 ng L-1
      for urine samples and 0.8-5.6 ng L-1 for blood samples. Recoveries from both
      blood and urine ranged from 85 to 102%, and within-day and between-day relative
      standard deviations were all less than 7.5%. The proposed method offers
      advantages in reduction of the exposure danger to toxic solvents used in
      conventional sample pretreatment, simplicity of the extraction processes,
      rapidity, and sensitivity enhancement. The method was successfully used to
      quantify pharmacologically active substances in human and animal (lamb, veal and
      pig) blood and urine. The hormones estrone and 17beta-estradiol were detected in
      virtually all samples, and so were other analytes such as acetylsalicylic acid,
      ibuprofen, ketoprofen and triclosan in human samples, and florfenicol,
      pyrimethamine and phenylbutazone in animal samples.

PMID- 22391331
TI  - A LC-MS/MS method to evaluate the hepatic uptake of the liver-specific magnetic
      resonance imaging contrast agent gadoxetate (Gd-EOB-DTPA) in vitro and in humans.
AB  - Gadoxetate (Gd-EOB-DTPA, Primovist(r)) is a frequently used liver-specific
      magnetic resonance imaging (MRI) contrast agent which disposition is so far not
      fully understood in humans. Here, we describe the development and validation of a
      selective and sensitive quantification method to measure cellular in vitro
      concentrations as well as human serum concentrations of gadoxetate. The drug was
      measured after protein precipitation with acetonitrile and ethyl acetate-mediated
      sample concentration using amoxicillin as internal standard and liquid
      chromatography coupled with tandem mass spectrometry (LC-MS/MS) for detection.
      Hydrophilic interaction chromatography (HILIC) was performed by using the column
      Atlantis(r) HILIC Silica (2.1 mm * 100 mm), a step-elution gradient with
      acetonitrile and ammonium acetate (5mM, pH 3.8) as mobile phases and a flow rate
      of 200 MUl/min. The MS/MS detection was done in the negative multiple reaction
      monitoring (MRM) mode by monitoring the m/z transitions 681.3/635.2 for
      gadotrexate and 363.8/222.7 for the internal standard. The method was validated
      between 5 and 4000 ng/ml in serum and between 1.25 and 500 ng/ml in cell lysates.
      The method was shown to possess sufficient specificity, accuracy, precision and
      stability without any matrix effects, thereby fulfilling current bioanalytical
      guidelines. The developed assay was successfully applied to quantify gadoxetate
      in cellular uptake studies in OATP1B1-transfected cell lines and to monitor serum
      concentrations-time profiles from a clinical pilot study performed in healthy
      volunteers carrying the wild-type or the functionally relevant variants T521C
      (*5) and A388G (*1b) of the hepatic uptake transporter OATP1B1.

PMID- 22391332
TI  - Interfacial microstructure and properties of carbon fiber composites modified
      with graphene oxide.
AB  - The performance of carbon fiber-reinforced composites is dependent to a great
      extent on the properties of fiber-matrix interface. To improve the interfacial
      properties in carbon fiber/epoxy composites, we directly introduced graphene
      oxide (GO) sheets dispersed in the fiber sizing onto the surface of individual
      carbon fibers. The applied graphite oxide, which could be exfoliated to single
      layer GO sheets, was verified by atomic force microscope (AFM). The surface
      topography of modified carbon fibers and the distribution of GO sheets in the
      interfacial region of carbon fibers were detected by scanning electron microscopy
      (SEM). The interfacial properties between carbon fiber and matrix were
      investigated by microbond test and three-point short beam shear test. The tensile
      properties of unidirectional (UD) composites were investigated in accordance with
      ASTM standards. The results of the tests reveal an improved interfacial and
      tensile properties in GO-modified carbon fiber composites. Furthermore,
      significant enhancement of interfacial shear strength (IFSS), interlaminar shear
      strength (ILSS), and tensile properties was achieved in the composites when only
      5 wt % of GO sheets introduced in the fiber sizing. This means that an
      alternative method for improving the interfacial and tensile properties of carbon
      fiber composites by controlling the fiber-matrix interface was developed. Such
      multiscale reinforced composites show great potential with their improved
      mechanical performance to be likely applied in the aerospace and automotive
      industries.

PMID- 22391333
TI  - Elimination diet effectively treats eosinophilic esophagitis in adults; food
      reintroduction identifies causative factors.
AB  - BACKGROUND & AIMS: Adults with eosinophilic esophagitis (EoE) typically present
      with dysphagia and food impaction. A 6-food elimination diet (SFED) is effective
      in children with EoE. We assessed the effects of the SFED followed by food
      reintroduction on the histologic response, symptoms, and quality of life in
      adults with EoE. METHODS: At the start of the study, 50 adults with EoE underwent
      esophagogastroduodenoscopies (EGDs), biopsies, and skin-prick tests for food and
      aeroallergens. After 6 weeks of SFED, patients underwent repeat EGD and biopsies.
      Histologic responders, defined by <= 5 eosinophils/high-power field (eos/hpf) (n
      = 32), underwent systematic reintroduction of foods followed by EGD and biopsies
      (n = 20). Symptom and quality of life scores were determined before and after
      SFED. RESULTS: Common symptoms of EoE included dysphagia (96%), food impaction
      (74%), and heartburn (94%). The mean peak eosinophil counts in the proximal
      esophagus were 34 eos/hpf and 8 eos/hpf, before and after the SFED, and 44
      eos/hpf and 13 eos/hpf in the distal esophagus, respectively (P < .0001). After
      the SFED, 64% of patients had peak counts <= 5 eos/hpf and 70% had peak counts of
      <= 10 eos/hpf. Symptom scores decreased in 94% (P < .0001). After food
      reintroduction, esophageal eosinophil counts returned to pretreatment values (P <
      .0001). Based on reintroduction, the foods most frequently associated with EoE
      were wheat (60% of cases) and milk (50% of cases). Skin-prick testing predicted
      only 13% of foods associated with EoE. CONCLUSIONS: An elimination diet
      significantly improves symptoms and reduces endoscopic and histopathologic
      features of EoE in adults. Food reintroduction re-initiated features of EoE in
      patients, indicating a role for food allergens in its pathogenesis. Foods that
      activated EoE were identified by systematic reintroduction analysis but not by
      skin-prick tests.

PMID- 22391334
TI  - Estimation of spatial-temporal gait parameters in level walking based on a single
      accelerometer: validation on normal subjects by standard gait analysis.
AB  - This paper investigates the ability of a single wireless inertial sensing device
      stuck on the lower trunk to provide spatial-temporal parameters during level
      walking. The 3-axial acceleration signals were filtered and the timing of the
      main gait events identified. Twenty-two healthy subjects were analyzed with this
      system for validation, and the estimated parameters were compared with those
      obtained with state-of-the-art gait analysis, i.e. stereophotogrammetry and
      dynamometry. For each side, from four to six gait cycles were measured with the
      device, of which two were validated by gait analysis. The new acquisition system
      is easy to use and does not interfere with regular walking. No statistically
      significant differences were found between the acceleration-based measurements
      and the corresponding ones from gait analysis for most of the spatial-temporal
      parameters, i.e. stride length, stride duration, cadence and speed, etc.;
      significant differences were found for the gait cycle phases, i.e. single and
      double support duration, etc. The system therefore shows promise also for a
      future routine clinical use.

PMID- 22391335
TI  - 12(S)-Hydroxyheptadeca-5Z,8E,10E-trienoic acid suppresses UV-induced IL-6
      synthesis in keratinocytes, exerting an anti-inflammatory activity.
AB  - 12(S)-Hydroxyheptadeca-5Z,8E,10E-trienoic acid (12- HHT) is an enzymatic product
      of prostaglandin H(2) (PGH(2)) derived from cyclooxygenase (COX)-mediated
      arachidonic acid metabolism. Despite the high level of 12-HHT present in tissues
      and bodily fluids, its precise function remains largely unknown. In this study,
      we found that 12-HHT treatment in HaCaT cells remarkably down-regulated the
      ultraviolet B (UVB) irradiation-induced synthesis of interleukin-6 (IL-6), a pro
      inflammatory cytokine associated with cutaneous inflammation. In an approach to
      identify the down-stream signaling mechanism by which 12-HHT down-regulates UVB
      induced IL-6 synthesis in keratinocytes, we observed that 12-HHT inhibits the UVB
      stimulated activation of p38 mitogen-activated protein kinase (MAPK) and nuclear
      factor kappa B (NF-kappaB). In addition, we found that 12-HHT markedly up
      regulates MAPK phosphatase-1 (MKP-1), a critical negative regulator of p38 MAPK.
      When MKP-1 was suppressed by siRNA knock-down, the 12-HHT-mediated inhibitory
      effects on the UVB-stimulated activation of p38 MAPK and NF-kappaB, as well as
      the production of IL-6, were attenuated in HaCaT cells. Taken together, our
      results suggest that 12-HHT exerts anti-inflammatory effect via up-regulation of
      MKP-1, which negatively regulates p38 MAPK and NF-kappaB, thus attenuating IL-6
      production in UVB-irradiated HaCaT cells. Considering the critical role of IL-6
      in cutaneous inflammation, our findings provide the basis for the application of
      12-HHT as a potential anti-inflammatory therapeutic agent in UV-induced skin
      diseases.

PMID- 22391336
TI  - The effectiveness of valerian acupressure on the sleep of ICU patients: a
      randomized clinical trial.
AB  - BACKGROUND: Severely ill patients often experience problems with sleep. Either
      acupressure or valerian aromatherapy are reported as helpful in promoting sleep.
      OBJECTIVES: The purpose of this study was to explore the effectiveness of
      valerian acupressure on the sleep of patients in the intensive care unit (ICU).
      DESIGN: A randomized clinical trial. SETTING: A 42-bed adult intensive care unit.
      PARTICIPANTS: Forty-one subjects in the experimental group and 44 subjects in the
      control group. METHODS: The measurement included observation, and actigraphy
      measures during 10 pm-6 am, and the Stanford Sleepiness Scale (SSS) measures on
      the next morning. Experimental groups received valerian acupressure on the
      Shenmen, Neiguan, and Yongquan acupoints between 7 pm and 10 pm of the second day
      while control groups received regular treatment. Heart rate was measured for 5
      min before and after valerian acupressure present for HR variability analysis to
      measure relaxation response. RESULTS: The results indicated that after receiving
      valerian acupressure, patients' sleeping hours increased, wake frequency reduced
      and SSS grades declined. The HR variability data indicated relaxation response
      immediately after valerian acupressure. CONCLUSION: This study supports the
      hypothesis that valerian acupressure on the Shenmen, Neiguan, and Yongquan
      acupoints could improve the sleeping time and quality of ICU patients.

PMID- 22391337
TI  - Emotional exhaustion and workarounds in acute care: cross sectional tests of a
      theoretical framework.
AB  - BACKGROUND: As health care organizations strive to improve their work processes,
      attention is being paid to workarounds in the clinical setting. Some research has
      found a link between burnout and workarounds. Other research shows that the
      clinical work environment can influence burnout levels in clinical workers,
      particularly emotional exhaustion. OBJECTIVE: Underpinned by Conservation of
      Resources theory, we examined a conceptual model linking the work environment
      with workarounds in acute care nurses and other clinicians, and hypothesized that
      burnout, specifically emotional exhaustion, would mediate these relationships.
      STUDY DESIGN AND SETTING: A cross sectional survey study was conducted in a large
      tertiary hospital in North America. PARTICIPANTS: All clinical care providers in
      the hospital's medical units were invited to participate. The response rate was
      45%, with nurses comprising 85% of respondents. METHOD: Questionnaires were
      mailed to employee homes using a two-wave methodology. RESULTS: Hypotheses were
      examined using structural equation modeling. Time pressure was positively related
      to exhaustion, and autonomy was negatively related. Exhaustion was positively
      related to workarounds, and mediated the time pressure and autonomy to
      workarounds relationships. Contrary to expectations, the physical environment was
      directly and negatively related to workarounds. CONCLUSION: Our findings suggest
      that the work environment may influence more than individual clinician well-being
      and exhaustion, it also may influence workaround behaviors that could lead to
      harm for patients and/or the organization. More attention should be paid to the
      mechanisms that influence workarounds.

PMID- 22391339
TI  - The association of obesity with the likelihood of arrest for young adults.
AB  - This paper examines whether obesity is associated with the likelihood of arrest.
      We hypothesize that obese individuals are less likely to commit crime and be
      arrested because their body weights may prevent them from successfully engaging
      in certain criminal activities, particularly those that are physically intensive.
      To test this hypothesis, we use the National Longitudinal Survey of Youth 1997
      and panel data techniques and find that obesity is negatively related to arrest.
      In one specification, for example, we found that the odds of an obese man being
      arrested are 64% of those of a healthy weight man. The social costs of obesity
      may be overstated if obesity reduces the likelihood of arrest because the obese
      are less criminally active.

PMID- 22391338
TI  - Fat chance! Obesity and the transition from unemployment to employment.
AB  - This paper focuses on estimating the magnitude of any potential weight
      discrimination by examining whether obese job applicants in Germany get treated
      or behave differently from non-obese applicants. Based on two waves of rich
      survey data from the IZA Evaluation dataset, which includes measures that control
      for education, demographic characteristics, labor market history, psychological
      factors and health, we estimate differences in job search behavior and labor
      market outcomes between obese/overweight and normal weight individuals. Unlike
      other observational studies which are generally based on obese and non-obese
      individuals who might already be at different points in the job ladder (e.g.,
      household surveys), in our data, individuals are newly unemployed and all start
      from the same point. The only subgroup we find in our data experiencing any
      possible form of negative labor market outcomes is obese women. Despite making
      more job applications and engaging more in job training programs, we find some
      indications that they experienced worse (or at best similar) employment outcomes
      than normal weight women. Obese women who found a job also had significantly
      lower wages than normal weight women.

PMID- 22391340
TI  - Transaortic Fallot repair in a grown-up patient: advantages in a situs inversus
      setting.
AB  - We present the case studies of two adult patients with tetralogy of Fallot who
      were scheduled for surgery. After addressing the right ventricular outflow tract
      obstruction, the aorta was opened and the ventricular septal defect was
      approached in a straightforward manner as it was located just under the
      overriding aortic valve. The second patient presented with was a situs inversus,
      dextroapex Fallot. In this setting, the aortic approach simplified the repair
      expeditiously. After 2 years, both patients are in New York Heart Association
      class I, with no residual ventricular septal defect, no aortic regurgitation, and
      complete relief of right ventricular outflow tract obstruction.

PMID- 22391341
TI  - Imitation of a bimanual task in preschool- and school-age children: a
      hierarchical construction.
AB  - The present study examined the development of bimanual interaction during the
      imitation of a live demonstration. To this end, children of five different age
      groups observed an adult model performing in an object manipulation task
      consisting to open a box with one hand, taking out an object with the other hand,
      and closing the box again, before they were asked to imitate this motor task
      under different imitation conditions. The children's responses were videotaped,
      coded in dichotomous data, and then transformed in percentage scores. The main
      results showed that all children were able to imitate/attain the goal of the
      task. However, differences were observed for the different imitation conditions,
      which were also reflected in some age effects, while hand dominance was a strong
      constraint on imitation. Also, practice did not seem to increase the likelihood
      of model imitation. These findings confirm that imitation is a reconstruction
      mechanism hierarchically organized.

PMID- 22391342
TI  - Lipopolysaccharide activates ERK-PARP-1-RelA pathway and promotes nuclear factor
      kappaB transcription in murine macrophages.
AB  - Poly(ADP-ribosyl)ation, like acetylation, methylation and phosphorylation, is one
      of the essential post-translational protein modifications. Poly(ADP-ribose)
      polymerase 1 (PARP-1), the best characterized member of the PARP family,
      catalyzes PAR formation, and has been implemented in the in vivo and in vitro
      inflammatory disease models. However, the exact signaling pathways leading to
      PARP-1 activation and the molecular mechanisms of activated PARP-1 signaling of
      inflammatory genes' expression remains to be further elucidated. In the present
      study, murine macrophages, in vitro stimulated with lipopolysaccharide (LPS),
      showed a profound activation of PARP-1, and PARP-1-dependent expression of mRNA
      for interleukin (IL)-1beta and IL-18 inflammatory cytokines. Immunoprecipitation
      assays showed that LPS stimulation enhanced the binding of PARP-1 with p65 (RelA)
      and poly(ADP-ribosyl)ation of p65, which might account for the upregulated
      transcription activity of nuclear factor (NF)-kappaB and the increased expression
      of proinflammatory genes. The application of various signal pathway inhibitors
      revealed that besides the canonical ROS-DNA damage signal, ERK pathway modulated
      the activation of PARP-1. ERK inhibitor blocked the interaction of PARP-1 with
      ERK1/2, phosphorylation of PARP-1, and poly(ADP-ribosyl)ation of p65, suggesting
      that ERK-dependent phosphorylation of PARP-1 regulates PARP-1 activity and NF
      kappaB activation. Taken together, our results suggest that an ERK-PARP-1-RelA
      pathway in macrophages promote inflammatory progression in septic diseases.

PMID- 22391343
TI  - Description and molecular modeling of a novel human leukocyte antigen allele:
      A*32:22.
AB  - We describe here the sequence and the molecular modeling of a new variant of HLA
      A*32 allele officially named A*32:22. This novel allele has been detected in an
      Italian cord blood sample by sequence-based typing (SBT). The mutation (CAT 
      >CGT), which has occurred at codon 151, at nucleotide position 524, implies an
      amino acidic change from Histidine to Arginine. Residue 151 is located on top of
      the molecule inside the region contacted by T cell receptor (TCR) and it is
      possibly involved in docking TCR. A positively charged residue is maintained on
      this position determining a slight change of electrostatic potential on the
      molecular surface. This suggests a limited functional relevance of the amino acid
      substitution encoded by A*32:22.

PMID- 22391344
TI  - Rifaximin improves systemic hemodynamics and renal function in patients with
      alcohol-related cirrhosis and ascites.
AB  - Circulating levels of endotoxin, interleukin (IL)-6, and tumor necrosis factor
      (TNF)-alpha increase with intestinal bacterial overgrowth and translocation, and
      are believed to be involved in the pathogenesis of hyperdynamic circulatory
      syndrome and functional renal failure in patients with advanced cirrhosis. We
      investigated the effects of the antibiotic rifaximin on systemic hemodynamics and
      renal function in patients with alcohol-related cirrhosis and ascites. We
      measured mean arterial pressure, cardiac output (CO) by Doppler ultrasound,
      systemic vascular resistance (as the ratio of mean arterial pressure:CO), plasma
      renin activity, levels of plasma aldosterone, the glomerular filtration rate by
      plasma clearance of technetium-99m-DTPA, natriuresis, levels of plasma endotoxin,
      and serum levels of IL-6 and TNF-alpha in 13 patients at baseline and after 4
      weeks of treatment with rifaximin. Rifaximin treatment significantly reduced CO
      and significantly increased systemic vascular resistance, in association with a
      significant decrease in plasma rennin activity. The therapy also significantly
      increased the glomerular filtration rate and natriuresis while reducing levels of
      endotoxin, IL-6, and TNF-alpha. Intestinal decontamination with rifaximin
      improved systemic hemodynamics and renal function in patients with advanced
      cirrhosis.

PMID- 22391345
TI  - Effect of renal impairment on mortality of patients with cirrhosis and
      spontaneous bacterial peritonitis.
AB  - BACKGROUND & AIMS: The effects of end-stage renal disease (ESRD) on the mortality
      of patients with cirrhosis and spontaneous bacterial peritonitis (SBP) have not
      been determined. METHODS: We collected data from Taiwan's National Health
      Insurance Database on 2592 patients with cirrhosis who were hospitalized with SBP
      from January 1 to December 31, 2004. Patients were matched with individuals from
      a national mortality database; 30-day and 1-year mortalities were calculated for
      each group and compared to calculate hazard ratios (HRs). RESULTS: Of the
      patients with cirrhosis and SBP, 300 (11.5%) had renal function impairment. Of
      these, 145 had acute renal failure, 70 had ESRD, and 75 had chronic kidney
      disease. Overall, 30-day and 1-year mortality were 21.3% and 51.7%, respectively.
      After adjusting for age, sex, and underlying comorbidities, HRs for 30-day
      mortality from renal function impairment, acute renal failure, ESRD, and chronic
      kidney disease were 3.00, 4.68, 1.93, and 1.37, respectively. The HRs for 1-year
      mortality from renal function impairment, acute renal failure, ESRD, and chronic
      kidney disease were 2.03, 2.78, 1.70, and 1.37, respectively. The adjusted HRs
      for 30-day and 1-year mortality of patients with acute renal failure were 2.6 and
      1.6, respectively, compared with patients with ESRD. CONCLUSIONS: Acute renal
      failure is a better determinant of 30-day and 1-year mortality than renal
      function impairment in cirrhotic patients with SBP.

PMID- 22391346
TI  - Rare cause of gastric outlet obstruction: incarcerated pylorus within an inguinal
      hernia.
AB  - We present the case of a 79-year-old man admitted to the emergency room. Having
      anorexia and vomiting as main complaints, combined with abdominal distension and
      discomfort, diagnostic examination revealed a giant left inguinal hernia
      containing the antrum and pylorus of a dilated stomach,  creating an outlet
      obstruction. This was complicated with free peritoneal air, gastric emphysema and
      air in the portal system due to ischaemia.

PMID- 22391347
TI  - Duodenal duplication complicating laparoscopic cholecystectomy: a case report.
AB  - Duplication of the gastrointestinal tract is an uncommon congenital abnormality
      that can occur anywhere from the tongue to the anus. The duodenum is the least
      common location for such an abnormality, which usually manifests as a spherical
      cyst-like structure that can present as mechanical  bowel obstruction, biliary
      obstruction or an abdominal mass, among other presentations. Such abnormalities
      are typically detected during childhood but here we report a case of duodenal
      duplication discovered as a complication of laparoscopic cholecystectomy in an
      adult.

PMID- 22391348
TI  - Subacute physeal abscess: case report to illustrate treatment with a minimally
      invasive incision and drainage technique.
AB  - INTRODUCTION: Brodie's abscess is a form of subacute osteomyelitis characterised
      by a low grade pyogenic abscess found most commonly in the metaphysis. One rare
      form found in children crosses the physeal growth plate and into the epiphysis.
      Due to the rarity of this subtype and  apprehension associated with treatment of
      the transphyseal abscess, no clear guidance exists on its management. CASE
      HISTORY: We present a case of delayed diagnosis of Brodie's abscess crossing the
      physis in a 14-year-old boy. He gave a one-year history of pain in the right knee
      and early x-rays had shown lucent areas in the tibia. However, these were only
      noted to be significant at presentation one year later. We also describe an
      improvised minimally invasive and atraumatic technique of modifying a laminar
      suction catheter for accessing and draining the abscess. CONCLUSIONS: From our
      experience and reports in the literature it is clear that antibiotic treatment is
      generally advocated with varying degrees of surgical intervention. Outcomes are
      largely favourable. Nevertheless, initial drainage allows samples to be sent for
      microbiological and histological assessment  to aid subsequent management and may
      prevent subsequent leg length discrepancy from failed conservative treatment. We
      believe that management of a transphyseal abscess must include early drainage and
      a prolonged course of antibiotics. The antibiotic choice and duration will be
      governed by  culture results and local policy but is commonly given for up to six
      weeks in the literature and must include one antistaphylococcal drug.

PMID- 22391349
TI  - Breast cancer presenting as subclavian/axillary deep vein thrombosis and upper
      limb lymphoedema.
AB  - This case report describes the delayed diagnosis of inflammatory breast cancer
      following initial presentation with a subclavian/axillary deep vein thrombus. The
      relationship of thrombosis and cancer is discussed and the typical presentation
      of inflammatory breast cancer described. Understanding  the relationship between
      thromboembolism and cancer is crucial to support the early diagnosis of breast
      cancer, which can present insidiously. The literature is reviewed, highlighting
      the improving prognosis of this rare condition and the current preferred
      treatment modalities.

PMID- 22391350
TI  - Isolated metastatic primary peritoneal carcinoma to the breast: a rare site of
      disease recurrence.
AB  - Primary breast carcinoma is a common pathology in the UK. It can present with
      metastatic deposits but it is rare that lesions in the breast are the sole
      primary or secondary presentation for metastatic cancer from other sources. We
      present a case of a primary peritoneal cancer recurring  after optimal treatment
      with a new breast lesion and the diagnostic difficulties that this can cause.

PMID- 22391351
TI  - Septic emboli resulting in an acutely ischaemic lower limb: a case report.
AB  - Sources of arterial embolism range from the common, such as cardiac pathology, to
      less common causes. We present a case of an acutely ischaemic lower limb due to
      septic emboli from Staphylococcus aureus pneumonia.

PMID- 22391352
TI  - A case of triple volvulus.
AB  - Situs inversus is a rare congenital anomaly that has reportedly been associated
      with caecal volvulus. We describe a case of partial situs inversus complicated by
      intestinal obstruction secondary to three simultaneously occurring volvuli of the
      stomach, caecum and sigmoid colon. To our  knowledge, this is the first
      documented case in the literature of multiple, simultaneously occurring volvuli.

PMID- 22391353
TI  - Reconstruction for basal cell carcinoma in an anatomical region where the sun
      does not shine: an attractive option!
AB  - Basal cell carcinoma is one of the common skin malignancies but it is rarely
      found in sun-protected areas. The soft tissue reconstruction at the perianal
      region can be challenging and a variety of options are described in the
      literature. The keystone design perforator island flap is  an excellent and
      attractive option for soft tissue reconstruction. We present a case of perianal
      basal cell carcinoma that was reconstructed with a unilateral keystone flap.

PMID- 22391354
TI  - Faecaloma in ano.
AB  - INTRODUCTION: Faecal concretions or faecalomas ('stone of faeces') are
      symptomatic of many well-recognised colorectal conditions. Faecalomas are usually
      located in the colon or rectum and associated with disorders of colorectal
      transit. We describe an unusual case of 'faecaloma  in ano' secondary to a
      chronic fissure in ano. A 67-year-old woman with a 10-year history of chronic
      constipation and intermittent anal discomfort presented with a painless perianal
      lump of similar duration. METHODS: The patient's case notes were reviewed and a
      literature search  was carried out. RESULTS: Examination under anaesthesia,
      sigmoidoscopy and anoscopy did not reveal any mucosal abnormality or an internal
      opening or any connection with the perianal lump. The mass was enucleated after
      incising the skin, leaving behind a cavity completely separate  from the anal
      canal and sphincters. Histology revealed inspissated faecal material with
      evidence of calcification. CONCLUSIONS: Chronic fissures may be complicated by
      sepsis and, rarely, a 'fissure fistula' may develop. We suspect that this was the
      underlying pathogenesis of this  'faecaloma in ano'. The term faecaloma in ano
      befits the clinical picture.

PMID- 22391355
TI  - Electrosurgery ignition of a pneumoperitoneum secondary to prior spontaneous
      perforation of the small bowel: a cautionary tale.
AB  - We describe explosive combustion of a gas filled peritoneum from a handheld
      electrosurgery electrode used to enter the abdomen. The pneumoperitoneum was due
      to small bowel perforation and peritonitis had been established for at least two
      days. No injury was caused to either the patient  or medical staff. This rare
      occurrence has only been described once before. Surgeons should be aware of the
      possible combustion of bowel gas, whether on opening bowel or the peritoneum
      after bowel perforation.

PMID- 22391356
TI  - Parastomal hernia causing gastric emphysema.
AB  - We report a case of a parastomal hernia in which the stomach became incarcerated.
      This is an unusual yet serious complication of parastomal hernias.

PMID- 22391357
TI  - Cervical pneumatocoele following total thyroidectomy.
AB  - Cervical pneumatocoele following thyroidectomy is rare. Urgent surgical
      intervention is necessary in the setting of widespread tissue emphysema and
      respiratory embarrassment. We describe a patient with a large pneumatocoele
      presenting six weeks after a total thyroidectomy who was managed  successfully
      without surgical re-exploration. We also discuss the aetiology of cervical
      pneumatocoele as well as the potential indications for operative versus
      conservative management.

PMID- 22391358
TI  - Local anaesthetics.
AB  - Although there are two types of LA, amides are now more commonly used.
      Understanding the pharmacology and physicochemical properties of LAs enables
      prediction of speed of onset, duration of action and determination of the correct
      LA for a particular clinical requirement. Drug concentration is expressed as a
      percentage such that 1% = 1 g/100 ml = 1,000 mg/100 ml = 10 mg/ml. Lipid rescue
      therapy has been shown to be a very effective treatment for LA toxicity.

PMID- 22391359
TI  - Gastrogastric herniation: an unusual complication following greater curve
      plication for the treatment of morbid obesity.
AB  - Greater curve plication is an emerging procedure for the treatment of morbid
      obesity. A median weight loss of up to 61% at one year has been reported in
      initial reports. Thus far, operative morbidity is low and there is no reported
      mortality. We present a case of gastric herniation  after greater curve
      plication. Severe nausea and vomiting occurred in our patient with an excessively
      tight greater curve plication. Two gastric hernias developed through the
      plication suture. Surgical reduction of these hernias and revision of the
      original procedure was required. We recommend  that greater curve plication is
      performed over a bougie and that two rows of closely spaced interrupted sutures
      are used to secure the plication.

PMID- 22391360
TI  - Cervical lymphocoele: a simple solution for a complicated problem.
AB  - Spontaneous cervical lymphocoeles are extremely rare. Their surgical management
      can pose many challenges with the lack of clear surgical planes potentiating
      risks. We present the case of a patient with an extensive right-sided cervical
      lymphocoele. Surgical excision would have involved  extensive surgery with risk
      to the great vessels and lungs. We describe the successful use of talc
      sclerotherapy in the management of this patient, who made a rapid post-operative
      recovery with no evidence of recurrence on follow-up. Talc sclerotherapy may be
      used successfully in the management  of patients with cervical lymphocoeles,
      obviating the need for high risk surgical procedures.

PMID- 22391361
TI  - The numeric threshold for the disclosure of risk: outdated and inapplicable to
      surgical consent.
AB  - When describing the risks of surgery to a patient, there is a common and mistaken
      supposition by surgeons that there exists a numeric threshold of improbability
      beyond which there is no need to disclose. Where should the line be drawn?

PMID- 22391362
TI  - An unusual case of desmoid tumour presenting as haemorrhagic shock.
AB  - We report the case of a 22-year-old patient who presented to the emergency
      department with epigastric pain and vomiting. Haematological studies showed a
      rapid decrease in haemoglobin levels from 13.6 g/dl to 4.9 g/dl. Abdominal
      ultrasonography revealed the presence of fluid around the spleen and the patient
      was immediately referred for surgery. An intra-abdominal desmoid tumour
      presenting as a hemorrhagic shock has not previously been described. Given the
      relatively benign course of the disease and the young age at presentation, this
      clinical entity should not be overlooked as it has the potential to invade
      vessels and therefore be fatal.

PMID- 22391363
TI  - A quick and effective method of limb preparation with health, safety and
      efficiency benefits.
AB  - INTRODUCTION: Pre-operative limb preparation (PLP) usually involves lifting the
      limb and holding it in a fixed 'static' posture for several minutes. This is
      hazardous to theatre staff. Furthermore, 'painting' the limb can be time
      consuming and difficult areas such as between  toes and fingers may remain
      unsterile. We demonstrate the time efficiency and asepsis achieved using the
      'sterile bag' preparation technique. An additional advantage is the ability to
      prepare and anaesthetise a limb prior to theatre, increasing efficiency
      substantially for units with a large  throughput of cases, such as day-case hand
      surgery lists. METHODS: We monitored the duration of PLP in 20 patients using the
      'sterile bag' technique compared to 20 patients using a conventional 'painting'
      method. Additionally, microbiology samples acquired from prepared upper limbs  of
      27 sequential patients operated on by a single surgeon over a two-month period
      were sent for culture immediately prior to commencement of surgery. RESULTS: The
      mean duration of the 'sterile bag' PLP was significantly lower than that of the
      conventional method (24 seconds vs 85  seconds, p=0.045). The technique can take
      as little as ten seconds (n=1). Final microbiology reports showed no growth for
      any of the 27 patients from whom a culture sample was taken. CONCLUSIONS: The
      sterile bag technique is effective in achieving asepsis, has the potential  to
      increase theatre efficiency and reduces manual handling hazards compared to the
      conventional method. It is now taught to all theatre staff in our hospital during
      manual handling training. It can be undertaken in approximately ten seconds with
      practice for the upper limb.

PMID- 22391364
TI  - Gastrojejunostomy: a potential hazard to the surgeon.
AB  - This case report highlights the potential hazard of emergency operating of an
      obstructed hollow viscus in the era of World Health Organization checklists.

PMID- 22391365
TI  - Phytobezoar: a rare cause of late upper gastrointestinal perforation following
      gastric bypass surgery.
AB  - Marginal ulcers are a well described complication following Roux-en-Y gastric
      bypass. These may be a cause for perforation. We describe a case of upper
      gastrointestinal perforation 18 months following a laparoscopic Roux-en-Y gastric
      bypass that appeared to be caused by a food bezoar.  The perforation occurred at
      the site of the jejunojejunal anastomosis and was repaired after an exploratory
      laparotomy. After extracting the food debris (phytobezoar) through the
      perforation, direct closure resulted in an uneventful post-operative recovery. To
      our knowledge, this is the first  description of a food bezoar causing an
      intestinal perforation in such a manor after bariatric surgery. Patients should
      be educated carefully on what and how to eat after having undergone surgery for
      superobesity.

PMID- 22391366
TI  - Alcohol skin preparation causes surgical fires.
AB  - INTRODUCTION: Surgical fires are a rare but serious preventable safety risk in
      modern hospitals. Data from the US show that up to 650 surgical fires occur each
      year, with up to 5% causing death or serious harm. This study used the National
      Reporting and Learning Service (NRLS)  database at the National Patient Safety
      Agency to explore whether spirit-based surgical skin preparation fluid
      contributes to the cause of surgical fires. METHODS: The NRLS database was
      interrogated for all incidents of surgical fires reported between 1 March 2004
      and 1 March 2011.  Each report was scrutinised manually to discover the cause of
      the fire. RESULTS: Thirteen surgical fires were reported during the study period.
      Of these, 11 were found to be directly related to spirit-based surgical skin
      preparation or preparation soaked swabs and drapes. CONCLUSIONS: Despite
      manufacturer's instructions and warnings, surgical fires continue to occur.
      Guidance published in the UK and US states that spirit-based skin preparation
      solutions should continue to be used but sets out some precautions. It may be
      that fire risk should be included in pre-surgical  World Health Organization
      checklists or in the surgical training curriculum. Surgical staff should be aware
      of the risk that spirit-based skin preparation fluids pose and should take action
      to minimise the chance of fire occurring.

PMID- 22391367
TI  - Splenic laceration with a twist: a lesson learnt from gastric volvulus.
AB  - Acute gastric volvulus is an uncommon entity that requires prompt diagnosis and
      management to prevent potential life threatening complications. We present a rare
      case of splenic laceration secondary to acute gastric volvulus.

PMID- 22391368
TI  - The effect of alcohol on surgical skills.
AB  - INTRODUCTION: The General Medical Council states 'a surgeon must not work when
      their health state is adversely influenced by fatigue, disease, drugs or
      alcohol'. However, there are no defined criteria for acceptable blood alcohol
      levels when operating. The aim of this study was  to measure the effect of
      varying amounts of alcohol on surgical dexterity, cognitive abilities and the
      social interactions required to ensure patient safety during a routine ear, nose
      and throat (ENT) operation. METHODS: ENT surgeons were asked to perform a
      microlaryngoscopy with  excision of a predetermined glottic lesion on a validated
      laryngeal model. The procedure was repeated four times over a period of four
      hours with varying doses of alcohol (no alcohol control, one glass, three glasses
      and six glasses of wine). The parameters recorded included theatre etiquette, 
      surgical time, operative skills and patient safety. Scores were adjudicated by
      two independent observers. RESULTS: The more glasses of wine consumed, the more
      detrimental the effect was on the surgical performance of all participants. There
      was a global reduction in ability of 7.25%  after three glasses and 19.25% after
      six glasses of alcohol. No domain showed an improvement following sequential
      increase in blood alcohol concentration. CONCLUSIONS: This study suggests that
      there are no deleterious effects on surgical performance following the
      consumption of one  glass of wine 45 minutes prior to microlaryngoscopy among ENT
      surgeons of varying experience. However, there is clear evidence that with three
      or more glasses of wine there is an adverse effect on performance, with decreased
      surgical dexterity, cognition functions and professionalism.

PMID- 22391369
TI  - Screening mammogram microcalcification due to basal cell carcinoma of the skin.
AB  - Basal cell carcinoma is the most common skin malignancy worldwide, typically
      presenting as a pearly or translucent papule. Histologically, approximately 21%
      contain areas of microcalcification. We report a case of a woman presenting with
      microcalcification on screening mammography that  was suspicious. Repeated core
      biopsies did not obtain microcalcification, and a diagnostic excision of breast
      tissue and overlying skin revealed an intradermal basal cell carcinoma containing
      the microcalcification. No breast malignancy was present. We believe this is the
      second such reported  case in the literature and the first to be reported in
      Europe.

PMID- 22391370
TI  - Intraductal papillary mucinous neoplasm of the oesophagus: an unusual case of
      dysphagia.
AB  - We report the case of a 58-year-old woman presenting with dysphagia secondary to
      an intraductal papillary mucinous neoplasm arising from a heterotopic pancreas in
      the oesophageal wall. This was successfully treated with a
      laparoscopic/thoracoscopic ivor Lewis oesophagectomy. Dysphagia  is the most
      common symptom of oesophageal tumours regardless of aetiology of the tumour and
      can be treated successfully with surgical resection. Through an extensive search
      of the literature, we found that a heterotopic pancreas in the oesophagus is
      extremely rare with only ten cases being  reported. We describe what we believe
      to be the first case of a heterotopic pancreas in the oesophagus transforming
      into an intraductal papillary mucinous neoplasm.

PMID- 22391371
TI  - The power of words: sources of anxiety in patients undergoing local anaesthetic
      plastic surgery.
AB  - INTRODUCTION: With local or regional anaesthesia being employed for more as well
      as more complex surgical procedures, an increasing number of patients remain
      fully conscious during their operation. This is generally perceived as being
      advantageous to the patient as less time  is spent in hospital and the side
      effects of general anaesthesia are avoided. However, there is no direct measure
      of the patient experience during 'awake surgery', in particular of which aspects
      of the process may be distressing. METHODS: Seventy patients undergoing day case
      plastic  surgery under local anaesthesia were asked to complete a short
      questionnaire immediately following their operation. This was designed to
      identify specific factors likely to either increase or reduce anxiety during
      surgery. The questionnaire was initially validated on a pilot group of ten
      patients. RESULTS: Unsurprisingly, painful stimuli such as injections were
      identified as potential stressors. More interestingly, the data highlighted that
      some commonly used surgical terms such as 'knife' and 'scalpel' provoke
      considerable anxiety in the conscious patient. This varied according to age and
      sex  with younger and female patients being most vulnerable. Other events
      identified as potential stressors, such as casual conversations and movements
      among theatre staff, were actually shown to be non-stressful and, in some cases,
      stress relieving. CONCLUSIONS: Technical jargon used  by surgical staff can
      elevate anxiety levels among patients who are awake for their operation. Careful
      consideration of the words we use may reduce this, particularly in female
      patients.

PMID- 22391372
TI  - Abdominal pain and two x-rays: spot the difference.
AB  - We present two patients with air found in the right upper quadrant on standard
      abdominal x-ray. One was diagnosed with pneumobilia and underwent elective
      surgery for a bilioenteric fistula. The other was diagnosed with portal vein gas
      and underwent an emergency exploratory laparotomy  at which a superior mesenteric
      artery embolism was found. The differential diagnostic criteria for pneumobilia
      and portal vein gas are described. If portal venous gas is found on x-ray in
      patients with abdominal pain, it is recommended that management is aggressive,
      meaning an emergency  exploratory laparotomy, because mortality in such cases is
      approximately 75%.

PMID- 22391373
TI  - Proximal anterior cruciate ligament avulsion treated with TightRope(r) fixation
      device.
AB  - Anterior cruciate ligament injury is an uncommon finding in children but when it
      does occur it is usually a result of tibial avulsion or, less commonly, a
      midsubstance tear. It is generally agreed that surgical fixation is a necessity.
      We present a case of proximal anterior cruciate  ligament avulsion and a new
      method of fixation.

PMID- 22391374
TI  - Percutaneous cholecystostomy as an alternative to cholecystectomy in high risk
      patients with biliary sepsis: a district general hospital experience.
AB  - INTRODUCTION: Cholecystectomy is the standard treatment for patients with acute
      cholecystitis. However, percutaneous cholecystostomy (PC) is an alternative for
      patients at high risk for surgery. We present our five-year clinical experience
      with the aim of evaluating the efficacy  of PC in high risk patients. METHODS: A
      retrospective review was performed on 30 consecutive patients who underwent PC at
      our institution. The indications for cholecystostomy, route of insertion,
      technical success, clinical improvement, length of hospitalisation, in-hospital
      or 30-day  mortality, complications, subsequent admissions and performance of
      interval cholecystectomy were recorded. The median follow-up period was 25 months
      (range: 1-52 months). RESULTS: Thirty-two PCs were performed in thirty patients
      (mean age: 76.1 years; range: 52-90 years).  The indications for PC were acute
      calculous cholecystitis (29/32), acalculous cholecystitis (1/32) and
      emphysematous cholecystitis (2/32). The route of insertion was transperitoneal
      for 22/32 PCs (68.8%) and transhepatic for 10/32 (31.2%). The procedure was
      technically successful in all patients  although 2/22 transperitoneal drains
      (9.1%) were dislodged subsequently. Twenty-seven PCs (84.4%) resulted in clinical
      improvement within five days. The in-hospital or 30-day mortality rate was 16.7%
      (5/30). Eleven patients (36.7%) had a subsequent cholecystectomy: 6 were
      laparoscopic and  5 converted to open procedures at a median interval of 58 days
      (range: 1-124 days). CONCLUSIONS: PCs are straightforward with few complications.
      Most patients improve clinically and the procedure can therefore be used as a
      definitive treatment in unfit patients or as a bridge  to surgery in those who
      might subsequently prove fit for a definitive operation.

PMID- 22391375
TI  - Inverted cyclops lesion after anterior cruciate ligament reconstruction.
AB  - We report the case of an inverted cyclops lesion limiting extension of the knee
      joint after a four-strand hamstring anterior cruciate ligament (ACL)
      reconstruction. One case has been reported previously following a bone-tendon
      bone reconstruction of the ACL but a similar case has not  been reported.

PMID- 22391376
TI  - Penile degloving: an unusual presentation of hidradenitis suppurativa.
AB  - Chronic hidradenitis suppurativa (HS) can cause lymphoedema, leading to novel
      presentations. We present the case of a man with chronic HS causing penile oedema
      and subsequent degloving. He underwent direct excision with a good result.
      Chronic HS patients should be warned about problems  related to lymphoedema and
      reviewed regularly to resolve problems early.

PMID- 22391377
TI  - The use of pre-operative computed tomography in the assessment of the acute
      abdomen.
AB  - INTRODUCTION: While there are a lot of data on the accuracy of computed
      tomography (CT) in diagnosing specific causes of an acute abdomen, there is very
      little information on the accuracy of CT in the acute general surgical admissions
      workload. We look at the diagnostic accuracy  of CT in patients presenting with
      an acute abdomen who ultimately required a laparotomy. METHODS: Patients who
      underwent an emergency laparotomy between 2008 and 2010 at Eastbourne District
      General Hospital with pre-operative CT on the same admission were included in the
      study. The  CT report was compared with the laparotomy and histology findings
      and, where a discrepancy existed, the original imaging was reviewed by a senior
      consultant blinded to the original report and laparotomy findings. RESULTS: A
      total of 196 emergency laparotomies were performed over  the 2-year period, with
      112 patients undergoing preoperative CT. Fifteen patients were excluded from the
      study due to missing notes. In the remaining 97 patients, 80 CT reports
      correlated with the final operative diagnosis, giving a diagnostic accuracy of
      82%. Of these, the on-call registrar  was the initial reporter in 37 scans, with
      a diagnostic accuracy of 78%. On review of the CT by a second consultant, this
      increased to 90 correlations, yielding an accuracy of 93%. Delay between CT and
      the operation did not significantly alter diagnostic accuracy, nor was there any
      statistically  significant reduction in accuracy in reports issued by on-call
      registrars. CONCLUSIONS: On first reporting, CT misses 18% of diagnoses that
      ultimately require operative intervention. Reducing the threshold for obtaining a
      second consultant radiologist review significantly improves  the diagnostic
      accuracy to 93%.

PMID- 22391378
TI  - Total preservation of patency and valve function after percutaneous
      pharmacomechanical thrombolysis using the Trellis(r)-8 system for an acute,
      extensive deep venous thrombosis.
AB  - Pharmacomechanical thrombolysis is being used increasingly for the treatment of
      deep vein thrombosis (DVT) and aims to reduce the severity of post-thrombotic
      syndrome. We report the case of a 60-year-old woman with extensive lower limb DVT
      that was treated using pharmacomechanical thrombolysis  leading to complete
      recovery of her deep venous system. The prompt use of pharmacomechanical
      thrombolysis for the acute management of extensive DVT should be considered when
      treating patients with extensive DVT in order to facilitate return of normal
      function.

PMID- 22391379
TI  - An unusual presentation of late oesophagojejunal anastomotic leak after total D2
      gastrectomy.
AB  - Oesophagojejunal anastomotic leak usually presents in the early post-operative
      period with abdominal pain and sepsis. We report a case of late anastomotic leak
      presenting as epigastric pain with hyperamylasaemia and discuss the differential
      diagnosis.

PMID- 22391380
TI  - Lesions of uncertain malignant potential (B3) on core biopsy in the NHS Breast
      Screening Programme: is the screening round relevant?
AB  - INTRODUCTION: Most women who have screening mammography and undergo subsequent
      open biopsy following an indeterminate core biopsy result are eventually found to
      have benign disease. However, a significant number have malignant disease and the
      rate of malignancy in such cases  may be influenced by various factors. This
      study examined the effect of the type of screening round (prevalent or incident)
      on the likelihood of breast cancer being present. METHODS: A total of 199 women
      who had NHS breast screening mammograms and subsequent indeterminate (B3) core 
      biopsy results followed by excision biopsy over an 11-year period in a single
      breast screening unit were reviewed. RESULTS: The rate of malignancy following
      excision of a lesion graded as B3 on core biopsy was 21% for women in the
      prevalent screening round compared to 33% in subsequent  rounds (Fisher's exact
      test, p=0.038). CONCLUSIONS: The incidence of malignancy associated with a B3
      core biopsy result appears to be related to the screening round in which the
      lesion is detected, being approximately 50% higher in the subsequent incident
      rounds compared to  the initial prevalent round. This finding may be useful in
      formulating management plans for women who have an indeterminate biopsy result.

PMID- 22391381
TI  - Testicular dislocation: the importance of scrotal examination in a trauma
      patient.
AB  - Testicular dislocation after blunt perineal trauma is a rare event and a
      diagnosis that can be easily overlooked. Careful examination can help facilitate
      early and appropriate treatment. Timely diagnosis and surgical management are of
      paramount importance to preserve normal spermatogenic  function in the dislocated
      testicle. We describe a case of testicular dislocation and discuss some of the
      issues surrounding diagnosis and treatment.

PMID- 22391382
TI  - Static monolateral external fixation for the Rolando fracture: a simple solution
      for a complex fracture.
AB  - INTRODUCTION: Rolando fractures are often difficult to manage because of their
      inherent instability. We describe a simple technique for the treatment of this
      fracture using the principle of ligamentotaxis, with a static, two-pin external
      fixator spanning the trapeziometacarpal joint, and present the results of a
      single-surgeon case series. METHODS: Eight consecutive patients (mean age: 32.8
      years) with Rolando fractures were treated using a Hoffmann II((r)) Micro small
      bone external fixator using blunt ended 2.0mm half pins, inserted into the
      trapezium and diaphysis of the first metacarpal. Functional outcome was assessed
      with the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score at a
      mean time of 2.7 years following the fracture (range: 4 months-6.0 years). The
      mean time to frame removal was 28 days. RESULTS: There were three cases of
      superficial pin site infection. Follow-up x-rays at four months did not
      demonstrate significant joint incongruity or malunion in any case. The mean
      QuickDASH score was 7.95 and all patients returned to their previous levels of
      activity. CONCLUSIONS: Although external fixation risks pin site infection, the
      results of this study support the use of spanning trapeziometacarpal external
      fixation for Rolando fractures as it reliably gives excellent functional
      outcomes.

PMID- 22391383
TI  - The cadaveric anatomy of the distal radius: implications for the use of volar
      plates.
AB  - INTRODUCTION: Fractures of the distal radius are common upper limb injuries,
      representing a substantial proportion of the trauma workload in orthopaedic
      units. With ever increasing advancements in implant technology, operative
      intervention is becoming more frequent. As growing  numbers of surgeons are
      performing operative fixation of distal radial fractures, an accurate
      understanding of the relevant surgical anatomy is paramount. The flexor carpi
      radialis (FCR) tendon forms the cornerstone of the Henry approach to the volar
      cortex of the distal radius. A number of  key neurovascular structures around the
      wrist are potentially at risk during this approach, especially when the FCR is
      mobilised and placed under retractors. METHODS: In order to clarify the safe
      margins of the FCR approach, ten fresh frozen human cadaver limbs were dissected.
      The  location of the radial artery, the median nerve, the palmar cutaneous branch
      of the median nerve and the superficial branch nerve were measured with respect
      to the FCR tendon. Measurements were taken on a centre-to-centre basis in the
      coronal plane at the watershed level. In addition, the  distances between the
      tendons of brachioradialis, abductor pollicis longus and flexor pollicis longus,
      and the radial artery and median nerve were measured to create a complete picture
      of the anatomy of the FCR approach to the distal radius. RESULTS: The structure
      most at risk was  the palmar cutaneous branch of the median nerve. It was located
      on average 3.4mm from the FCR tendon. The radial artery and the main trunk of the
      median nerve were located 7.8mm and 8.9mm from the tendon. The superficial branch
      of the radial nerve was 24.4mm from the FCR tendon and 11.1mm  from the
      brachioradialis tendon. CONCLUSIONS: Operative intervention is not without
      complication. We believe a more accurate understanding of the surgical anatomy is
      key to the prevention of neurovascular damage arising from the surgical
      management of distal radial fractures.

PMID- 22391384
TI  - Arterial injuries at the elbow carry a high risk of muscle necrosis and warrant
      urgent revascularisation.
AB  - INTRODUCTION: Revascularisation following axial arterial system injury is
      effective in upper limb salvage but necrosis of muscle, the tissue most sensitive
      to ischaemia, may still occur. We examined the frequency of necrosis, its related
      factors and its functional significance. METHODS: The clinical findings and
      operative management of 13 patients with injuries at the elbow referred to 2
      plastic surgical hand surgery units over a 30-month period were reviewed. Good
      outcome was defined as minimal impairment with return to previous occupation,
      intermediate outcome as moderate  impairment with change in occupation and poor
      outcome as major functional loss preventing work. RESULTS: Seven patients injured
      the brachial and six injured both the radial and ulnar arteries. Concomitant
      injuries were severe with nerve injuries in 11 and muscle damage in 12 patients. 
      Functional outcome was good in four cases, intermediate in four and poor in five.
      Muscle necrosis developed in four brachial artery injuries. In all four cases,
      initial successful revascularisation failed post-operatively. Case review
      revealed delayed recognition in three cases where pain  heralded ischaemia but
      distal skin circulation and pulses were adequate. Of patients with necrosis,
      three had a poor outcome and one had an intermediate outcome. CONCLUSIONS: The
      risk of muscle necrosis must be considered when managing these injuries,
      particularly if initial revascularisation  is unsuccessful. Every effort should
      be made to optimise repair technique and post-operative monitoring. Limb salvage
      is no longer enough. Fully viable muscle is necessary to restore function and
      livelihoods.

PMID- 22391386
TI  - A simple technique to ensure adequate moulding of a cast into the Edinburgh
      position.

PMID- 22391385
TI  - Accuracy of prediction equations for calculating resting energy expenditure in
      morbidly obese patients.
AB  - INTRODUCTION: The accuracy of prediction equations for estimating resting energy
      expenditure (REE) in morbidly obese patients is unclear. The aim of this study
      was to compare the REE measured using bedside indirect calorimetry with commonly
      used prediction equations. METHODS: A total of 31 morbidly obese patients were
      studied. Pre-operative REE was measured with indirect calorimetry and compared
      with estimated REE using the Harris-Benedict and Schofield equations. All
      patients subsequently underwent a Roux-en-Y gastric bypass and measurements were
      repeated at six weeks and three months following surgery. RESULTS: The mean age
      of the patients was 47 years. The mean pre-operative body mass index was 46
      kg/m(2). The mean REE measured using indirect calorimetry was 1,980 kcal/day. The
      estimated REE using the Harris-Benedict and Schofield formulae was 2,195 and
      2,129 kcal/day respectively. The equations overestimated REE by 10% and 7%. Body
      weight and body mass index reduced significantly following Roux-en-Y gastric
      bypass. There was no significant change in measured REE over the three-month
      period. After weight loss the difference between the estimated and measured REE
      reduced to 1-3%. CONCLUSIONS: Prediction equations overestimate REE in morbidly
      obese patients. Their accuracy improved after surgery induced weight loss,
      confirming their validity for the normal weight population. Indirect calorimetry
      should be used in morbid obesity.

PMID- 22391388
TI  - How the Newcastle Thousand Families birth cohort study has contributed to the
      understanding of the impact of birth weight and early life socioeconomic position
      on disease in later life.
AB  - Much has been made of the potential influence of birth weight and early
      socioeconomic disadvantage in influencing adult health, but little has been
      published in terms of how important these associations may be with respect to
      exposures throughout the lifecourse. The objective of this review is to describe
      the contributions of the Newcastle Thousand Families Study in understanding the
      relative impacts of factors in early life, particularly birth weight and socio
      economic position at birth, in influencing health in later life. The Newcastle
      Thousand Families Study is a prospective birth cohort established in 1947. It
      originally included all births to mothers resident in Newcastle upon Tyne, in
      northern England, in May and June of that year. Study members were followed
      extensively throughout childhood and intermittently in adulthood. At the age of
      49-51 years, study members underwent a large-scale follow-up phase enabling an
      assessment of how early life may influence their later health, and also
      incorporating adult risk factors which enabled the relative contributions of
      factors at different stages of life to be assessed. While some findings from the
      study do support birth weight and early socio-economic position having influences
      on adult health status, the associations are generally small when compared to
      risk factors later in life. Using path analyses on longitudinal data of this
      nature enables mediating pathways between early life and later health to be
      assessed and if more studies were to take this approach, the relative importance
      of early life on adult disease risk could be better understood.

PMID- 22391389
TI  - Recurrent chromosomal breakpoints in patients with myelodysplastic syndromes and
      complex karyotype versus fragile sites.

PMID- 22391390
TI  - Characterization of sporulation histidine kinases of Paenibacillus polymyxa.
AB  - Sporulation histidine kinases, which sense sporulation-specific signals and
      initiate phosphorelay reactions, are poorly conserved among Bacillus species. We
      found several putative genes for sporulation histidine kinases in the genome
      sequence of Paenibacillus polymyxa E681 and assayed the genes for complementation
      of sporulation mutants of Bacillus subtilis. One of these genes, Kin1377,
      significantly restored the sporulation deficiency of kinA kinB double mutant of
      B. subtilis, but not of B. subtilis spo0B mutant. These results indicated that
      Kin1377 requires B. subtilis Spo0B and possibly Spo0F to transfer phosphate to B.
      subtilis Spo0A. Another putative kinase, Kin1038, slightly restored the
      sporulation deficiencies of both kinA kinB double mutant and spo0B mutant of B.
      subtilis. However the sporulation deficiency of the B. subtilis spo0B mutant was
      significantly restored in the presence of both Kin1038 and P. polymyxa Spo0A.
      These results indicate that the overexpressed Kin1038 is able to interact
      directly with and activate P. polymyxa Spo0A, and that Spo0A can support spore
      formation in B. subtilis.

PMID- 22391391
TI  - CuInSe2 (CIS) thin films prepared from amorphous Cu-In-Se nanoparticle precursors
      for solar cell application.
AB  - CuInSe(2) (CIS) absorber layers for thin film solar cells were formed via a
      nonvacuum route using nanoparticle precursors. A low-temperature colloidal
      process was used to prepare nanoparticles by which amorphous Cu-In-Se
      nanoparticles were formed within 1 min of reaction without any external heating.
      Raman spectra of the particles revealed that they were presumably mixtures of
      amorphous Cu-Se and In-Se binaries. Selenization of the precursor film prepared
      by doctor blade coating of the Cu-In-Se nanoparticles resulted in a facile growth
      of the particles up to micrometer scale. However, it also left large voids in the
      final film, which acted as short circuiting paths in completed solar cells. To
      solve this problem, we applied a solution-filling treatment in which a solution
      containing Cu and In ions was additionally coated onto the precoated
      nanoparticles, resulting in a complete infiltration of the filler solution into
      the pores in the nanoparticles based film. By this approach, short circuiting of
      the device was significantly mitigated and a conversion efficiency of up to 1.98%
      was obtained.

PMID- 22391392
TI  - Effects of dispersion of fiber orientation on the mechanical property of the
      arterial wall.
AB  - Effects of dispersion of the fiber orientation on the mechanical property of the
      arterial wall in health and disease subjected to the combined internal pressure
      and axial loading are examined within the framework of the finite deformation
      hyper-elasticity theory. Taking into account the residual stress, a two layer
      thick-walled circular cylindrical tube model with the fiber-reinforced
      incompressible composite hyper-elastic material is employed. Stress-radius curves
      and stress distributions of the arterial wall are given in health and disease
      considering dispersion of the fiber orientation. With instability/bifurcation
      analysis, it is found that not only the uniform inflation of the arterial wall in
      health, but also the instability or bifurcation problem for the arterial wall in
      disease may be described by this model.

PMID- 22391394
TI  - Molecular characterization of cytochrome P450 CYP6B47 cDNAs and 5'-flanking
      sequence from Spodoptera litura (Lepidoptera: Noctuidae): its response to lead
      stress.
AB  - In insects, P450s are responsible for the oxidative metabolism of structurally
      diverse endogenous and exogenous compounds including plant allelochemicals and
      insecticides. A novel full-length P450 cDNA, CYP6B47, was cloned from Spodoptera
      litura (Lepidoptera: Noctuidae). The sequence is 1718 bp in length with an ORF of
      1509 bp encoding 503 amino acid residues. The phylogenetic analysis indicated
      that CYP6B47 belongs to CYP3 clan and second clade of CYP6Bs which contain 11
      P450s from Noctuidae. Quantitative real-time PCR showed that CYP6B47 was
      expressed only in larvae stages and had a high level of transcription in the
      midgut and fat body. In addition, we cloned a 2141-bp 5'-flanking regions and
      presented the basal luciferase activities of promoter. We also predicted multiple
      putative elements for transcription factors binding in the 5'-flanking region.
      Interestingly, the expression of CYP6B47 significantly increased in the midgut
      and fat body after lead (Pb) exposure for 5 generations. Larvae tolerance to the
      alpha-cypermethrin (35% increased in LC(50)) and fenvalerate (52% increased in
      LC(50)) were improved after pre-exposure to 50 mg/kg Pb. These dates suggested
      that lead increased tolerance of larvae to insecticides mainly through
      transcriptional induction of detoxification genes including CYP6B47.

PMID- 22391399
TI  - Very small size proteoliposomes derived from Neisseria meningitidis: an effective
      adjuvant for antigen-specific cytotoxic T lymphocyte response stimulation under
      leukopenic conditions.
AB  - Leukopenia is a severe condition resulting from both pathological processes and
      some treatments, like chemotherapy in cancer patients. However, the activation of
      the patient immune system is required for the success of immunotherapeutic
      strategies, as cancer vaccines. In this regard, leukopenia constitutes a major
      hurdle to overcome, mainly due to the impairment of cytotoxic T lymphocyte (CTL)
      responses. Adjuvants are basic components of vaccine formulations, which might be
      useful to stimulate immunity under this immunosuppressed condition. To this aim,
      we tested the capacity of a novel nanoparticulated complex, very small size
      proteoliposomes (VSSP), to promote CTL even in a leukopenic scenario. Noteworthy,
      we observed that a VSSP-based OVA vaccine induced a normal antigen-specific CTL
      response in mice rendered leukopenia by the administration of high doses of the
      chemotherapeutic agent cyclophosphamide (CY), while under the same conditions the
      OVA antigen formulated in the TLR-3 agonist polyinosinic-polycytidylic acid
      (P(I:C)) was ineffective. Moreover, an appropriate combination of VSSP with the
      P(I:C) vaccine was able to restore the CD8(+) T cell effector function in
      leukopenic mice. VSSP induced not only a faster repopulation of immune cells in
      CY-receiving animals, but also enhanced the recovery of memory T lymphocytes and
      myeloid dendritic cells (DCs) while simultaneously abrogated the
      immunosuppressive capacity of myeloid-derived suppressor cells (MDSCs). Our
      results suggest that VSSP could be a particularly suitable immunomodulator to be
      used in CTL-promoting active immunotherapy strategies operating in severe immune
      compromised scenarios.

PMID- 22391400
TI  - Immune responses and protective efficacy of a recombinant swinepox virus
      expressing HA1 against swine H1N1 influenza virus in mice and pigs.
AB  - Swine influenza virus (SIV) is not only an important respiratory pathogen in pigs
      but also a potent threat to human health. Although immunization with recombinant
      poxviruses expressing protective antigens as vaccines has been widely used for
      against many infectious diseases, development of recombinant swinepox virus
      (rSPV) vector for the purpose has been less successful. Here, we report the
      construction of a recombinant swinepox virus (rSPV-HA1) expressing hemagglutinin
      (HA1) of H1N1 SIV. Immune responses and protection efficacy of the vaccination
      vector were evaluated in both the mouse model and the natural host: pig. Prime
      and boost inoculations of rSPV-HA1 yielded high levels of neutralization antibody
      against SIV and elicited potent H1N1 SIV-specific IFN-gamma response from T
      lymphocytes. Complete protection of pigs against H1N1 SIV challenge was observed.
      No pigs showed evident systemic and local reactions to the vaccine and no SIV
      shedding was detected from pigs vaccinated with rSPV-HA1 after challenge. Our
      data demonstrated that the recombinant swinepox virus encoding HA1 of SIV H1N1
      may serve as a promising SIV vaccine for protection against SIV infection.

PMID- 22391401
TI  - Developing evidence-based immunization recommendations and GRADE.
AB  - The Strategic Group of Advisory Experts (SAGE) on immunization is an independent
      advisory committee with a mandate to advise the World Health Organization (WHO)
      on the development of vaccine and immunization related policies. SAGE working
      groups are established on a time-limited basis to review and provide evidence
      based recommendations, together with their implications, for open deliberation
      and decision-making by SAGE. In making its recommendations, SAGE takes into
      consideration: the epidemiologic and clinical characteristics of the disease;
      vaccine and immunization characteristics; economic analysis; health system
      considerations; the existence of and interaction with other intervention and
      control strategies; costing and social impacts; and legal and ethical concerns.
      Since 1998, WHO has produced evidence-based vaccine position papers for use
      primarily by national public health officials and immunization programme
      managers. Since April 2006 all new or updated position papers have been based on
      SAGE recommendations. The Grading of Recommendations Assessment, Development and
      Evaluation (GRADE) approach has been adopted by WHO and, since 2008, GRADE tables
      that rate the quality of evidence have been produced in support of key
      recommendations. SAGE previously expressed concern that GRADE was not ideally
      suited to many immunization-specific issues such as the vaccine population level
      effect and the inclusion of surveillance system data, particularly for vaccine
      safety. Extensive productive interactions with various advisory groups including
      the US Advisory Committee on Immunization Practices, the European Centres for
      Disease Control, the German Standing Committee on Vaccination (STIKO), WHO's
      Global Advisory Committee on Vaccine Safety and the GRADE working group resulted
      in key enhancements to accommodate vaccine-relevant evidence. This facilitated
      integration and acceptability of the GRADE approach in the development of
      immunization related SAGE and WHO recommendations. Ongoing utilisation should
      result in further fine-tuning of the approach to ensure that recommendations are
      based on the full range of appropriate evidence.

PMID- 22391402
TI  - Ventriculocoronary fistulae in a patient with transposition of the great
      arteries, hypoplastic left heart, and pulmonary atresia.
AB  - We present a rare case of ventriculocoronary fistulae in a patient with d
      transposition of the great arteries, hypoplastic left heart, and pulmonary
      atresia. To our knowledge, this is the first report of this anatomic variant, and
      raises an important discussion about the development and implications of such
      fistulous connections.

PMID- 22391403
TI  - Methodology and interpretation of radiographic outcomes in surgically treated
      pelvic fractures:  a systematic review.
AB  - OBJECTIVE: To identify and evaluate previously described methods for the
      measurement, and interpretation, of radiographic outcomes of operatively treated
      pelvic fractures. DATA SOURCES: A systematic review of the available literature
      was performed using all major databases (MEDLINE, EMBASE, MEDLINE IN-PROGRESS,
      and Cochrane Central) in August 2009. STUDY SELECTION: Inclusion criteria were
      case series, cohort studies, or clinical trials regarding orthopaedic treatment
      of acute traumatic pelvic ring fractures treated surgically in adults, with at
      least 12 weeks of radiographic follow-up. Exclusion criteria were case reports or
      case series of <10 patients, review articles, foreign language articles, and
      series where time frame of outcome measurement was not stated were excluded. DATA
      EXTRACTION: Modality, and timeline, of the radiographic assessment was recorded.
      Next, the description of the method of radiographic measurement technique used
      was scrutinized for standardization. The interpretation of the radiographic
      measurement was evaluated, and any grading scale used was recorded. The
      interpretation of the quality of the radiographic result as described by each
      author was recorded. Finally, a qualitative methodological analysis was
      performed. DATA SYNTHESIS: Number of standardized radiographic assessment
      techniques used (3 of 31) and interpretation scales used (13 of 31) were
      calculated. Nonweighted mean follow-up time (30.6 months) and overall positive
      radiographic outcomes were calculated (78.6% good or excellent). CONCLUSIONS:
      Reporting of radiographic outcomes in pelvic fractures has been done using
      largely unstandardized and universally untested measurement techniques. The
      interpretations of these measurements are also inconsistent and untested.
      Substantive future research is needed in this area.

PMID- 22391404
TI  - Plunging when drilling:  effect of using blunt drill bits.
AB  - OBJECTIVE: Plunging when drilling can be a detrimental factor in patient care.
      There is, although, a general lack of information regarding the surgeon's
      performance in this skill. The aim of this study was to determine the effect that
      using sharp or blunt instruments had on the drill bit's soft tissue penetration,
      using a simulator. MATERIALS AND METHODS: Surgeons taking part in an
      International Trauma Course were invited to participate. Two groups were defined:
      experienced and inexperienced surgeons. Twelve holes were drilled in the
      following order: 3 holes with a sharp drill bit in normal bone (SNB), 3 holes
      with a sharp drill bit in osteoporotic bone (SOB), 3 holes with a blunt drill bit
      in normal bone, and 3 holes with a blunt drill bit in osteoporotic bone. Mean
      values and Student t tests were used for statistical analysis. RESULTS: Thirty
      seven surgeons participated, 20 experienced and 17 inexperienced surgeons. Mean
      plunging depths for SNB, SOB, blunt drill bit in normal bone, and blunt drill bit
      in osteoporotic bone were, respectively, 5.1, 5.4, 21.1, and 13.9 mm for
      experienced surgeons and 7.6, 7.7, 22, and 15.9 mm for inexperienced surgeons.
      Drilling with SNB and with SOB was statistically different, with inexperienced
      surgeons plunging 2.5 mm (P = 0.31) and 2.6 mm (P = 0.042) deeper, respectively.
      There was a difference (P < 0.001) between sharp and blunt drill bits in all
      drilling conditions for both the groups. CONCLUSIONS: Our study showed a
      significant difference in plunging depth when sharp or bunt drill bit was being
      used. Surgeons, regardless of their experience level, penetrate over 20 mm in
      normal bone and over 10 mm in osteoporotic bone.

PMID- 22391405
TI  - Radiostereometric analysis in measurements of migration and inducible micromotion
      in intra-articular distal radius fractures treated with a volar plate.
AB  - OBJECTIVES: This study examined the use of radiostereometric analysis (RSA) in
      the assessment of fixation stability and healing characteristics in intra
      articular fractures of the distal radius treated with a volar locking plate.
      DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS: Fifteen
      patients between 39 and 67 years of age with OTA type C distal radius fractures.
      INTERVENTION: All fractures were treated with a locked volar plate, and tantalum
      markers were inserted into fracture fragments. RSA was performed at 2, 6, 12, 18,
      and 52 weeks postoperatively. RSA measurements were also performed using maximal
      voluntary grip to create inducible micromotion at the fracture site at 6, 12, 18,
      and 52 weeks. MAIN OUTCOME MEASUREMENTS: Interfragmentary migration and inducible
      micromotion in terms of translation and rotation in 3 orthogonal axes were
      determined. The total translation and rotation were also calculated. RESULTS:
      Precision of measurements along individual axes was between 0.08 and 0.17 mm and
      0.70-0.94 degrees for migration and between 0.04 and 0.07 mm and 0.29 and 0.86
      degrees for inducible micromotion. Fractures underwent significant translational
      and rotational migration (P = 0.004 for both) during the first 2 weeks after
      surgery. This permanent migration was not detectable on conventional radiographs.
      Inducible fracture micromotion, measured during maximal grip, was detectable up
      to 18 weeks, even after achievement of radiographic union. CONCLUSIONS: RSA seems
      to have the potential to be a unique tool in redefining the biologic progress of
      fracture union. In plated fractures of the distal radius, the method is
      technically challenging due to difficulties in achieving a good scatter and
      visibility of tantalum RSA markers. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 22391407
TI  - Cervical carotid artery stenosis: latest update on diagnosis and management.
AB  - Carotid atherosclerotic disease is implicated in 15% to 30% of all ischemic
      strokes. Carotid endarterectomy has been the standard treatment for carotid
      artery atherosclerosis, but carotid angioplasty and stenting have emerged as a
      less-invasive treatment alternative. In this article, we review the recent
      literature on the epidemiology, pathophysiology, investigations, and treatment
      for atherosclerotic carotid artery disease, focusing on the role of carotid
      endarterectomy and carotid angioplasty and stenting in the treatment of
      symptomatic and asymptomatic carotid lesions.

PMID- 22391409
TI  - Body image satisfaction among Norwegian adolescents and young adults: a
      longitudinal study of the influence of interpersonal relationships and BMI.
AB  - This study used a latent growth curve modeling approach to examine body image
      satisfaction in 1132 Norwegian adolescent and adult males and females measured at
      six times between ages 13 and 30. An additional model examined the long term
      influence of parent-child relationship, peer relationship (both relationships
      assessed at age 13), and BMI (measured at each interval) to the patterns of
      change. The results showed a linear growth in body image satisfaction through
      adolescence followed by a stabilizing of the latent curve in adulthood for both
      genders. There were gender and developmental variations in the relative
      contributions of parents and peers for the slope and quadratic growth and in the
      contribution of BMI to body image satisfaction. When controlling for BMI, initial
      parent-child relationships and peer relationship predicted the variance in slope
      growth for males. Parent-child relationship predicted quadratic growth for males.
      Among females, only initial peer relationships predicted linear growth. No effect
      was found for quadratic growth. BMI had an additional negative effect on body
      image satisfaction during adulthood.

PMID- 22391408
TI  - Chest CT incidentalomas: thyroid lesions, enlarged mediastinal lymph nodes, and
      lung nodules.
AB  - A computed tomography (CT) incidentaloma is an incidentally detected and
      previously unsuspected finding or abnormality that is not related to the
      indication for obtaining the CT examination. The aim of this article is to review
      the frequency of incidentalomas on chest CT scans, discuss the potential clinical
      significance of the findings, and suggest guidelines for reporting, further
      evaluation, and follow-up, with particular focus on thyroid lesions, enlarged
      mediastinal lymph nodes and lung nodules.

PMID- 22391410
TI  - A comparison of eating, exercise, shape, and weight related symptomatology in
      males with muscle dysmorphia and anorexia nervosa.
AB  - In the context of the lack of nosological clarity surrounding muscle dysmorphia,
      this paper aims to compare the symptomatic profile of muscle dysmorphia and
      anorexia nervosa in males whilst using measures sensitive to indexing male body
      image concerns. Twenty-one male muscle dysmorphia patients, 24 male anorexia
      nervosa patients, and 15 male gym-using controls completed the Eating Disorder
      Examination-Questionnaire, the Muscle Dysmorphia Disorder Inventory, the
      Compulsive Exercise Test, and a measure of appearance-enhancing substance use.
      Men with muscle dysmorphia and anorexia nervosa demonstrated widespread
      symptomatic similarities spanning the domains of disturbed body image, disordered
      eating, and exercise behaviour, whilst differences were consistent with the
      opposing physiques pursued in each condition. Furthermore, correlational analyses
      revealed significant associations between scores on muscle dysmorphia and eating
      disorder measures. The present findings provide moderate support for the notion
      that muscle dysmorphia may be nosologically similar to anorexia nervosa.

PMID- 22391412
TI  - CyrA, a matricellular protein that modulates cell motility in Dictyostelium
      discoideum.
AB  - CyrA, an extracellular matrix (slime sheath), calmodulin (CaM)-binding protein in
      Dictyostelium discoideum, possesses four tandem EGF-like repeats in its C
      terminus and is proteolytically cleaved during asexual development. A previous
      study reported the expression and localization of CyrA cleavage products CyrA-C45
      and CyrA-C40. In this study, an N-terminal antibody was produced that detected
      the full-length 63kDa protein (CyrA-C63). Western blot analyses showed that the
      intracellular expression of CyrA-C63 peaked between 12 and 16h of development,
      consistent with the time that cells are developing into a motile, multicellular
      slug. CyrA immunolocalization and CyrA-GFP showed that the protein localized to
      the endoplasmic reticulum, particularly its perinuclear component. CyrA-C63
      secretion began shortly after the onset of starvation peaking between 8 and 16h
      of development. A pharmacological analysis showed that CyrA-C63 secretion was
      dependent on intracellular Ca(2+) release and active CaM, PI3K, and PLA2. CyrA
      C63 bound to CaM both intra- and extracellularly and both proteins were detected
      in the slime sheath deposited by migrating slugs. In keeping with its purported
      function, CyrA-GFP over-expression enhanced cAMP-mediated chemotaxis and CyrA-C45
      was detected in vinculin B (VinB)-GFP immunoprecipitates, thus providing a link
      between the increase in chemotaxis and a specific cytoskeletal component.
      Finally, DdEGFL1-FITC was detected on the membranes of cells capped with
      concanavalin A suggesting that a receptor exists for this peptide sequence.
      Together with previous studies, the data presented here suggests that CyrA is a
      bona fide matricellular protein in D. discoideum.

PMID- 22391411
TI  - Umbilical cord stem cells released from alginate-fibrin microbeads inside
      macroporous and biofunctionalized calcium phosphate cement for bone regeneration.
AB  - The need for bone repair has increased as the population ages. The objectives of
      this study were to (1) develop a novel biofunctionalized and macroporous calcium
      phosphate cement (CPC) containing alginate-fibrin microbeads encapsulating human
      umbilical cord mesenchymal stem cells (hUCMSC) and, for the first time, (2)
      investigate hUCMSC proliferation and osteogenic differentiation inside the CPC. A
      macroporous CPC was developed using calcium phosphate powder, chitosan, and a gas
      foaming porogen. Five types of CPC were fabricated: a CPC control, CPC+0.05%
      fibronectin (Fn), CPC+0.1% Fn, CPC+0.1% arginine-glycine-aspartate (RGD), and
      CPC+0.1% Fn+0.1% RGD. Alginate-fibrin microbeads containing 10(6) hUCMSC per ml
      were encapsulated in the CPC paste. After the CPC had set, the degradable
      microbeads released hUCMSC within it. The hUCMSC proliferated inside the CPC,
      with the cell density after 21 days being 4-fold that on day1. CPC+0.1% RGD had
      the highest cell density, which was 4-fold that of the CPC control. The released
      cells differentiated along the osteogenic lineage and synthesized bone mineral.
      The hUCMSC inside the CPC+0.1% RGD construct expressed the genes alkaline
      phosphatase, osteocalcin and collagen I, at twice the level of the CPC control.
      Mineral synthesis by hUCMSC inside the CPC+0.1% RGD construct was 2-fold that in
      the CPC control. RGD and Fn incorporation in the CPC did not compromise its
      strength, which matched the reported strength of cancellous bone. In conclusion,
      degradable microbeads released hUCMSC which proliferated, differentiated and
      synthesized minerals inside the macroporous CPC. The CPC with RGD greatly
      enhanced cell function. The novel biofunctionalized and macroporous CPC-microbead
      hUCMSC construct is promising for bone tissue engineering applications.

PMID- 22391413
TI  - Effect of persistent activation of phosphoinositide 3-kinase on heart.
AB  - AIMS: Insulin/insulin-like growth factor-1 (IGF-1) signaling plays an important
      role in many biological processes. The class IA isoform of phosphoinositide 3
      kinase (PI3K) is an important downstream effector of the insulin/IGF-1 signaling
      pathway. The aim of this study is to examine the effect of persistent activation
      of PI3K on gene expression and markers of cellular senescence in murine hearts.
      MAIN METHODS: Transgenic mice expressing a constitutively active PI3K in a heart
      specific manner were analyzed at the ages of 3 and 20 months. Effects of
      persistent activation of PI3K on gene expression were comprehensively analyzed
      using microarrays. KEY FINDINGS: Upon comprehensive gene expression profiling,
      the genes whose expression was increased included those for several heat shock
      chaperons. The amount and nuclear localization of a forkhead box O (FOXO) protein
      was increased. In addition, the gene expression of insulin receptor substrate-2
      decreased, and that of phosphatase and tensin homolog deleted on chromosome ten
      (PTEN) increased, suggesting that the persistent activation of PI3K modified the
      expression of molecules of insulin/IGF-1 signaling. The expression of markers of
      cellular senescence, such as senescence-associated beta-galactosidase activity,
      cell cycle inhibitors, proinflammatory cytokines, and lipofuscin, did not differ
      between old wild-type and caPI3K mice. SIGNIFICANCE: The persistent activation of
      PI3K modified the expression of molecules of insulin/IGF-1 signaling pathway in a
      transgenic mouse line. Markers of cellular senescence were not changed in the
      aged mutant mice.

PMID- 22391415
TI  - Novel application of polyelectrolyte multilayers as nanoscopic closures with
      hermetic sealing.
AB  - Closure systems for personnel protection applications, such as protective
      clothing or respirator face seals, should provide effective permeation barrier to
      toxic gases. Currently available mechanical closure systems based on the hook and
      loop types (example, Velcro) do not provide adequate barrier to gas permeation.
      To achieve hermetic sealing, we propose a nonmechanical, nanoscopic molecular
      closure system based on complementary polyelectrolyte multilayers, one with a
      polycation outermost layer and the other with a polyanion outermost layer. The
      closure surfaces were prepared by depositing polyelectrolyte multilayers under a
      variety of deposition conditions, on conformable polymer substrates (thin films
      of polyethylene teraphthalate, PET or polyimide, PI). The hermetic sealing
      property of the closures was evaluated by measuring the air flow resistance using
      the dynamic moisture permeation cell (DMPC) at different humidity conditions. The
      DMPC measurements show that the polyelectrolyte multilayer closures provide
      significantly large resistance to air flow, approximately 20-800 times larger
      than that possible with conventional hook and loop type closure systems, at all
      humidity levels (from 5 to 95% relative humidity). Hence, from the point of view
      of providing a hermetic seal against toxic gas permeation, the polyelectrolyte
      multilayer closures are viable candidates for further engineering development.
      However, the adhesive strength of the multilayer closures measured by atomic
      force microscopy suggests that the magnitude of adhesion is much smaller than
      what is possible with mechanical closures. Therefore, we envisage the development
      of a composite closure system combining the mechanical closure to provide strong
      adhesion and the multilayer closure to provide hermetic sealing.

PMID- 22391414
TI  - Rapid functional upregulation of vasocontractile endothelin ETB receptors in rat
      coronary arteries.
AB  - AIMS: Endothelin ET(B) receptors mediate under normal physiological conditions
      vasorelaxation in coronary arteries. However, vasocontractile ET(B) receptors
      appear in coronary arteries of ischemic heart disease patients. Interestingly,
      organ culture of isolated coronary arteries also induces upregulation of
      vasocontractile ET(B) receptors. This study examines the early time course and
      mechanism behind upregulation of contractile ET(B) receptors in isolated rat
      coronary arteries during short-term organ culture. MAIN METHODS: Coronary artery
      segments were mounted in wire-myographs and incubated in physiological saline
      solution. Contractions were measured after exposure to the specific ET(B)
      receptor agonist Sarafotoxin 6c (S6c) and the endogenous agonists endothelin-1
      and endothelin-3. Protein localization and levels of ET(B) and phosphorylated
      extracellular-signal-regulated-kinase-1/2 (ERK1/2) were examined by
      immunohistochemistry. KEY FINDINGS: Fresh arteries showed negligible
      vasoconstriction to S6c. However, incubation for only 4 and 7h increased S6c
      contractions two- and seven-fold, respectively. Furthermore, 7h incubation
      enhanced vasocontractile responses to endothelin-3 and increased ET(B) receptor
      density in vascular smooth muscle cells. ERK1/2 was activated rapidly after start
      of incubation. Moreover, incubation with either the transcriptional inhibitor
      actinomycin D or the mitogen-activated-protein kinase kinase 1/2 (MEK1/2)
      inhibitor U0126 attenuated contractile ET(B) receptor upregulation. U0126
      attenuated ET(B) receptor protein levels after 24 h of incubation. SIGNIFICANCE:
      Coronary arteries rapidly upregulate vasocontractile ET(B) receptors during organ
      culture via transcriptional mechanisms and MEK-ERK1/2 signalling. This model may
      mimic the mechanisms seen in ischemic conditions. Furthermore, these findings
      have important experimental implications in tissue bath experiments lasting for
      more than 4h.

PMID- 22391417
TI  - Using baby books to change new mothers' attitudes about corporal punishment.
AB  - OBJECTIVE: Research has found corporal punishment to have limited effectiveness
      in altering child behavior and the potential to produce psychological and
      cognitive damage. Pediatric professionals have advocated reducing, if not
      eliminating its use. Despite this, it remains a common parenting practice in the
      US. METHODS: Using a three-group randomized design, this study explored whether
      embedding educational information about typical child development and effective
      parenting in baby books could alter new mothers' attitudes about their use of
      corporal punishment. Low-income, ethnically diverse women (n=167) were recruited
      during their third trimester of pregnancy and followed until their child was 18
      months old. RESULTS: Findings from home-based data collection throughout this
      period suggest that educational baby books compared with non-educational baby
      books or no books can reduce new mothers' support for the use of corporal
      punishment (respective effect sizes=.67 and .25) and that these effects are
      greater for African-American mothers (effect sizes=.75 and .57) and those with
      low levels of educational attainment (high school diploma, GED, or less) (effect
      sizes=.78 and .49). CONCLUSION: Given their low cost and ease of implementation,
      baby books offer a promising way to change new mothers' attitudes and potentially
      reduce the use of corporal punishment with infants and toddlers.

PMID- 22391418
TI  - Infant with altered consciousness after cannabis passive inhalation.

PMID- 22391416
TI  - Childhood sexual abuse moderates the association between sexual functioning and
      sexual distress in women.
AB  - OBJECTIVE: To assess the degree to which a history of childhood sexual abuse
      (CSA) moderates the association between sexual functioning and sexual distress in
      women. METHOD: Women with (n=105, M age=33.71, 66.1% Caucasian) and without
      (n=71, M age=32.63, 74.7% Caucasian) a history of CSA taking part in a larger
      clinical trial completed self-report questionnaires at intake including the
      Sexual Satisfaction Scale for Women (SSS-W), the Female Sexual Function Index
      (FSFI), and the Trauma History Questionnaire (THQ). RESULTS: Desire, arousal,
      lubrication, and orgasm interacted with sexual abuse status in predicting sexual
      distress such that sexual functioning was more weakly associated with distress
      for women with a history of CSA. This disconnect was more pronounced for women
      who were abused by a family member. CONCLUSION: CSA status serves as an important
      moderator of the association between sexual functioning and sexual distress in
      women. Specifically, women with a history of CSA show higher levels of distress
      in the context of good sexual functioning as compared to women without a history
      of CSA. Possible explanations and clinical implications are discussed.

PMID- 22391419
TI  - Redesigning the NEDD8 pathway with a bacterial genetic screen for ubiquitin-like
      molecule transfer.
AB  - Pathways of ubiquitin-like (UBL) molecule transfer regulate a myriad of cellular
      cascades. Here, we report a high-throughput assay that correlates catalytic human
      NEDD8 transfer to bacterial survival. The assay was utilized to screen mutant
      NEDD8 and NAE (NEDD8-activating enzyme) libraries to engineer a more stable NEDD8
      and redesign the NEDD8-NAE interface. This approach will be useful in
      understanding the specificities underlying UBL pathways.

PMID- 22391421
TI  - Anti-LRP/LR-specific antibody IgG1-iS18 significantly reduces adhesion and
      invasion of metastatic lung, cervix, colon and prostate cancer cells.
AB  - The 37-kDa/67-kDa laminin receptor [laminin receptor precursor/high-affinity
      laminin receptor (LRP/LR)] is thought to play a major role in invasion and
      adhesion, key components of metastatic cancer. Lung cancer, cervical cancer,
      colon cancer and prostate cancer are among the top 10 cancer types worldwide.
      Here, we report that LRP/LR levels on the surface of lung cancer cells, cervical
      cancer cells, colon cancer cells and prostate cancer cells are significantly
      increased compared to non-tumorigenic fibroblasts. Adhesion of lung cancer cells,
      cervical cancer cells, colon cancer cells and prostate cancer cells to laminin-1
      is significantly reduced, employing the anti-LRP/LR-specific antibody IgG1-iS18.
      Invasion of these cell lines into the MatrigelTM matrix was significantly impeded
      with IgG1-iS18. The Pearson's correlation coefficient proves a correlation
      between LRP/LR cell-surface levels and invasion potential, as well as adhesion
      and invasion, respectively. Our findings suggest that IgG1-iS18 antibody might
      act as alternative therapeutic tool for treatment of various metastatic cancer
      types.

PMID- 22391420
TI  - Engineered oligomerization state of OmpF protein through computational design
      decouples oligomer dissociation from unfolding.
AB  - Biogenesis of beta-barrel membrane proteins is a complex, multistep, and as yet
      incompletely characterized process. The bacterial porin family is perhaps the
      best-studied protein family among beta-barrel membrane proteins that allows
      diffusion of small solutes across the bacterial outer membrane. In this study, we
      have identified residues that contribute significantly to the protein-protein
      interaction (PPI) interface between the chains of outer membrane protein F
      (OmpF), a trimeric porin, using an empirical energy function in conjunction with
      an evolutionary analysis. By replacing these residues through site-directed
      mutagenesis either with energetically favorable residues or substitutions that do
      not occur in natural bacterial outer membrane proteins, we succeeded in
      engineering OmpF mutants with dimeric and monomeric oligomerization states
      instead of a trimeric oligomerization state. Moreover, our results suggest that
      the oligomerization of OmpF proceeds through a series of interactions involving
      two distinct regions of the extensive PPI interface: two monomers interact to
      form a dimer through the PPI interface near G19. This dimer then interacts with
      another monomer through the PPI interface near G135 to form a trimer. We have
      found that perturbing the PPI interface near G19 results in the formation of the
      monomeric OmpF only. Thermal denaturation of the designed dimeric OmpF mutant
      suggests that oligomer dissociation can be separated from the process of protein
      unfolding. Furthermore, the conserved site near G57 and G59 is important for the
      PPI interface and might provide the essential scaffold for PPIs.

PMID- 22391424
TI  - Premature myocardial infarction is associated with low serum levels of Wnt-1.
AB  - OBJECTIVE: Besides its effects on glucose and lipid metabolism, the Wnt pathway
      has been increasingly implicated in the regulation of proliferation, migration
      and survival of vascular cells. In addition, defective Wnt signaling has been
      identified in a family with autosomal dominant early coronary artery disease. The
      aim of this study was to investigate whether premature coronary artery disease is
      associated with features of decreased Wnt signaling. METHODS AND RESULTS: We
      prospectively enrolled 100 consecutive young survivors of myocardial infarction
      (MI<=40 years of age) from two high-volume cardiac catheterization centers and
      100 sex and age matched hospital controls. We determined serum levels of Wnt-1
      and its antagonist Dkk-1 by ELISA. MI patients showed significantly lower Wnt-1
      levels as compared to controls (151 ng/mL, IQR 38-473 ng/mL vs. 233 ng/mL, IQR 62
      1756; p<0.005) whereas Dkk-1 was not different at baseline. Wnt-1 levels remained
      stable over time, whereas Dkk-1 significantly increased at one-year follow-up
      from 3557, IQR 2306-5810 pg/mL to 4973, IQR 3293-7093 pg/mL (p<0.001). In the
      stable phase of the disease, Wnt-1 levels were lower (p<0.005) and Dkk-1 levels
      were significantly higher (p<0.001) as compared to controls. Wnt-1 at follow-up
      was associated with glucose, HbA1c, non-HDL-, HDL-cholesterol and triglyceride
      levels but no other features of the metabolic syndrome. CONCLUSION: This study
      establishes an association between low Wnt-1 and high Dkk-1 serum levels and
      premature myocardial infarction. Wnt-1 is associated with markers of glucose and
      lipid metabolism. Further research elucidating the role of Wnt pathways in
      premature coronary artery disease and metabolic syndrome is warranted.

PMID- 22391425
TI  - The growing interest of fibrin imaging in atherosclerosis.

PMID- 22391426
TI  - [Neurosyphilis after treatment of syphilitic hepatitis in an immunocompetent
      patient].

PMID- 22391427
TI  - [Royal Decree on biobanks].

PMID- 22391428
TI  - [Knowledge and adherence to pneumococcal vaccination recommendations in adults
      among family physicians and hospital specialists].

PMID- 22391429
TI  - Incidence of nodal disease after nonsurgical therapy in head and neck squamous
      cell carcinoma patients with bilateral neck disease: can a bilateral neck
      dissection be avoided?
AB  - BACKGROUND: We evaluated whether classifying 1 side of a patients' neck as "high
      risk" would help in deciding the extent of neck dissection in patients with
      bilateral nodal disease. METHODS: We conducted a retrospective review of 44
      patients (88 heminecks) with head and neck squamous cell carcinoma who had
      bilateral nodal disease and received definitive chemoradiotherapy (CRT). For
      lateralized lesions (70%), the ipsilateral neck was designated as the "high-risk"
      neck. For midline lesions, pre-CRT and post-CRT computed tomography scans were
      used to stage each side of the neck (hemineck); the higher staged hemineck was
      designated as the "high-risk" neck. RESULTS: Twenty-seven patients had died at
      the time of analysis. Patients had a median follow-up of 27.8 months (range, 6 to
      150 mo). Two-year neck control and overall survival were 83% and 56%,
      respectively. Sixty-two heminecks (71%) were dissected. A total of 6/22 (27%)
      "low-risk" necks were positive after CRT if the "high-risk" neck was positive
      versus 0/22 if the "high-risk" neck was negative (P=0.02). CONCLUSIONS:
      Identifying the more "high-risk" neck may be useful when deciding the extent of
      neck dissection after CRT. For patients with bilateral nodal disease treated with
      CRT, dissection of the "low-risk" hemineck may be omitted if the "high-risk" neck
      is pathologically negative.

PMID- 22391430
TI  - Characterization and outcomes of small cell carcinoma of the bladder using the
      surveillance, epidemiology, and end results database.
AB  - OBJECTIVE: To utilize the Surveillance, Epidemiology, and End Results Database to
      analyze clinical features, treatment, and survival outcomes of patients with
      small cell carcinoma of the bladder in a large population-based sample. Because
      of its rarity, prior reports are primarily limited to small single-institution
      studies. METHODS: We identified patients of any age who were diagnosed with small
      cell carcinoma of the bladder between 1988 and 2007. Kaplan-Meier and Cox
      regression analysis were used to compare overall survival (OS) and urinary
      bladder-specific survival. RESULTS: A total of 663 patients were identified. Most
      patients had either stage II (38.8%) or stage IV (35.4%) disease. The median OS
      for all patients was 12 months [95% confidence interval (CI), 10.9-13.1]. After
      excluding those patients who presented with distant metastatic disease or for
      whom it was unknown whether or not they received any treatment, there were no
      significant differences in survival between those that received cystectomy
      (median survival, 21 mo; 95% CI, 14.3-27.7) compared with those who underwent
      external beam radiation (median survival, 17 mo; 95% CI, 13.4-20.6). On
      multivariate analysis, both cystectomy (hazard ratio, 0.53; 95% CI, 0.4-0.71; P <
      0.001) and radiation (hazard ratio, 0.66; 95% CI, 0.5-0.88; P=0.005) were
      associated with improved survival. CONCLUSIONS: Small cell carcinoma of the
      bladder is a rare but aggressive malignancy with poor OS. For those who present
      without widespread metastatic disease, treatment with either cystectomy or
      radiation appears to improve survival. Further prospective studies are needed to
      determine the best approach for treatment of these patients.

PMID- 22391431
TI  - The effectiveness of erlotinib against brain metastases in non-small cell lung
      cancer patients.
AB  - BACKGROUND: Brain metastases commonly occur in non-small cell lung cancer
      (NSCLC), and patient prognosis is poor. Erlotinib, a specific inhibitor of
      epidermal growth factor receptor-associated tyrosine kinase, has shown antitumor
      activity in advanced NSCLC. This study evaluates erlotinib in the treatment for
      brain metastases from NSCLC. PATIENTS AND METHODS: We retrospectively reviewed 40
      NSCLC patients with brain metastases. All were treated with oral erlotinib and
      followed until disease progression, death, or intolerable side effects. EGFR
      mutations within surgical specimens were retrospectively examined in 9 patients.
      RESULTS: For intracranial diseases, partial response (PR) was observed in 4
      patients (10%), stable disease (SD) in 21 (52.5%), and progressive disease in 15
      (37.5%), with an objective response rate of 10% and a disease control rate (DCR)
      of 62.5%. For extracranial diseases, DCR was observed in 17 patients (42.5%) (3
      PRs+14 SDs) and progressive disease in 23 patients (57.5%). DCR within brain
      lesions in patients with activating EGFR mutations was 80% (1 PR+3 SDs), compared
      with 25% (1 SD) in patients with negative EGFR mutation. The median progression
      free survival and median survival were 3.0 months and 9.2 months, respectively.
      There were no clinical factors associated with the response to erlotinib and
      survival as well (all P>0.05), whereas only the DCR in the brain was related to
      survival in multivariate analysis (P=0.000). CONCLUSIONS: Erlotinib is modestly
      active and well-tolerated by NSCLC patients with brain metastases. Erlotinib
      seems to be more effective in patients with activating EGFR mutations. Erlotinib
      may be an alternative to traditional treatments in this patient population.

PMID- 22391432
TI  - Utilization of proton therapy: evidence-based, market-driven, or something in
      between?
AB  - OBJECTIVES: Proton therapy (PT) is a potentially promising, but costly, radiation
      modality. Assessment of such new health technologies is becoming increasingly
      important in the era of constrained budgets. This study attempts to establish how
      PT utilization might fit into the existing radiation oncology armamentarium.
      MATERIALS AND METHODS: All patients treated in 2007 with radiation therapy at an
      academic institution were individually evaluated as potential PT candidates.
      Seven potential adoption scenarios were developed, ranging from PT being superior
      (A), to being clinically reasonable with some published evidence (B1-B3), to
      being clinically appealing but without published evidence (C). Two sensitivity
      analyses (D and E) were also performed. RESULTS: One thousand forty-two patients
      were treated using 19,749 treatment fractions. PT could be used in 6% of
      treatment courses and 3% of treatment fractions in scenario A, in 12% and 7% in
      scenario B1, in 17% and 17% in scenario B2, in 8% and 17% in scenario B3, in 24%
      and 30% in scenario C, in 37% and 30% in scenario D, and 67% and 79% in scenario
      E. Introduction of PT would increase treatment delivery cost over baseline by 2%,
      2%, 18%, 27%, 45%, 29%, and 141%, respectively. CONCLUSIONS: The degree of PT
      utilization would depend on the strictness of selection criteria, and would
      likely range from 6% to 25%, with concomitant cost increase from minimal to 40%.
      Ultimate adoption of PT in the United States may depend on individual facilities
      and payors performing similar analyses and setting individual adoption criteria.

PMID- 22391433
TI  - The efficacy of high-dose 3-dimensional conformal radiation therapy in patients
      with small hepatocellular carcinoma not eligible for other local modalities.
AB  - PURPOSE: To analyze the efficacy and toxicity of high-dose 3-dimensional
      conformal radiation therapy (3D-CRT) for patients with small hepatocellular
      carcinoma (HCC) not eligible for other local modalities. METHODS: Between 1998
      and 2006, 61 patients with small HCC were treated with high-dose 3D-CRT. The
      eligibility criteria were as follows: (1) HCC <5 cm; (2) HCC without vascular
      invasion; (3) HCC without extrahepatic metastasis; and (4) not eligible for other
      local modalities. The median RT dose was 54 Gy (range, 36 to 55 Gy) daily in 2.5
      to 5 Gy fractions. We evaluated tumor response, local control, overall survival,
      pattern of failure, and toxicity. RESULTS: The median follow-up period was 16.7
      months. Tumor response was 68.9% (42 of 61 lesions) with a complete response in
      27 lesions (44.3%). Local control was 93.8% at 1 year and 86.9% at 3 years.
      Intrahepatic metastases developed in 40 patients (65.6%). Thirteen patients
      (22.3%) had extrahepatic metastasis. The median survival was 56 months (range,
      2.8 to 68.1 mo), and the overall survival rate was 81.1% at 1 year and 58.4% at 3
      years. Three patients developed radiation-induced liver disease, but there were
      no instances of grade 3 or higher toxicity. CONCLUSIONS: High-dose 3D-CRT for
      small HCC <5 cm showed favorable local control and overall survival without
      serious complications. RT might be an effective local modality in patients with
      small HCC not eligible for other local modalities.

PMID- 22391434
TI  - Association of DiGeorge anomaly and caudal dysplasia sequence in a neonate born
      to a diabetic mother.
AB  - AIM/OBJECTIVE: Several studies have demonstrated a significantly increased risk
      of specific patterns of congenital anomalies in infants born to diabetic mothers.
      In particular, caudal dysplasia sequence has been linked to pregnancy complicated
      by maternal diabetes. In addition, several cases of infants born to diabetic
      mothers presenting with features of DiGeorge anomaly have been reported. Infants
      with DiGeorge anomaly can display additional manifestations within the spectrum
      of caudal dysplasia sequence, including vertebral anomalies and renal agenesis.
      METHODS: We report a neonate presenting with the co-occurrence of features of
      both DiGeorge anomaly and caudal dysplasia sequence, born to a mother with poorly
      controlled insulin-dependent diabetes. RESULTS: The patient was affected by
      truncus arteriosus type A1 and hypertrophic cardiomyopathy. CONCLUSION: Maternal
      diabetes can cause a spectrum of manifestations, expressing with isolated
      DiGeorge anomaly or caudal dysplasia sequence, with intermediate phenotypes or
      with the co-occurrence of both the congenital anomalies in the same patient. The
      present observations argue for a feasible link between truncus arteriosus with
      hypertrophic cardiomyopathy, DiGeorge anomaly, and maternal diabetes.

PMID- 22391435
TI  - Effect of early life housing manipulation on baseline and drug-induced
      behavioural responses on neurochemistry in the male rat.
AB  - Employing environmental enrichment (EE) provides continual sources of dynamic
      interaction for animals. Though an established discipline in behavioural science,
      the consequences of EE on behavioural pharmacological tests have not been
      extensively examined. The purpose of this study was to examine the consequences
      of EE (or isolation housing) on a range of behavioural pharmacological tests and
      brain monoamine and brain-derived neurotrophic factor (BDNF) expression in the
      rat. Male rats were randomly assigned to IC (isolation), SC (standard group
      housed) or EE conditions. IC and SC animals were housed singly or in groups of
      four in standard cages, whilst the EE group were housed in groups of four in
      larger cages enriched with a variety of wooden, cardboard and plastic objects.
      After 5weeks of housing, its impact on the effects of diazepam (DZP) in the
      elevated plus maze (EPM); desipramine (DMI) in the forced swim test (FST) and
      amphetamine (AMP) effects on homecage activity were assessed. Post-mortem
      monoamine and BDNF levels were analysed using HPLC and ELISA. EE rats displayed
      reduced activity in the OFT, however no other differences were found in baseline
      behaviours. DMI reduced immobility time in the FST, but only for rats housed in
      IC, while AMP effects were somewhat greater for socially-housed animals than
      those in IC. There were no housing effects on monoamine or BDNF levels in
      discreet brain regions. The results suggest that post-weaning enrichment had no
      significant effect on baseline behaviours or monoamine and BDNF levels, thus it
      is suitable to implement as a commonplace husbandry practice, however, caution
      must be taken when investigating responsiveness to psychotropic drugs.

PMID- 22391436
TI  - Total shoulder arthroplasty for the treatment of failed hemiarthroplasty in
      patients with fracture of the proximal humerus.
AB  - BACKGROUND: Little information is available for the outcomes of conversion to
      total shoulder arthroplasty (TSA) of failed hemiarthroplasty (HA) implanted for
      fractures or fracture-dislocations of the proximal humerus. MATERIALS AND
      METHODS: We evaluated the clinical and radiographic results in 16 patients who
      underwent conversion of HA to TSA due to pain and shoulder disfunction. Patients
      were a mean age of 63 years at revision, which was occurred a mean of 3.3 years
      after the HA. The main prerequisites for conversion were forward flexion to at
      least 60 degrees , no massive cuff tear, or severe resorption or nonunion of the
      tuberosities. In all cases, a modular prosthesis was used in the HA, uncemented
      in 14 and cemented in 2. The latest follow-up was a mean of 4.6 years after
      revision. RESULTS: The mean Constant score was 50.6 (range, 33-69), with an
      average increase of 11.9 points compared with the preoperative score (P = .001).
      In 75% of patients, the mean score was 54.6 (average increase, 15.1 points). The
      lowest scores occurred in patients with a cemented prosthesis that needed to be
      removed, and in 1 patient who had loosening of the implanted glenoid that was
      revised. CONCLUSIONS: Conversion of HA to TSA can improve the preoperative
      condition in most patients aged in their 50s or 60s in the absence of rotator
      cuff deficiency and severe bone loss of the proximal humerus.

PMID- 22391437
TI  - Electromagnetic navigation bronchoscopy (ENB): Increasing diagnostic yield.
AB  - OBJECTIVES: To determine factors associated with diagnostic yield of ENB.
      METHODS: In 112 consecutive patients referred to our department between March
      2010 and December 2010 the diagnostic work-up for solitary pulmonary lesions
      included a FDG-PET-CT scan, and ENB in combination with ROSE. The final diagnosis
      was confirmed by histopathological evaluation of specimen obtained either by ENB,
      or - if ENB was not diagnostic - by CT-guided fine needle aspiration or surgery.
      RESULTS: Thirty-seven (33%) subjects were female, mean age was 66.7 (+/-1.04)
      years. The mean diameter of lesions was 27mm (range: 6-46mm). In 83.9% the
      combination of PET-CT, ENB, and ROSE established a correct diagnosis, as defined
      by the definite histopathological result. 15.2% (17/112) of lesions were benign,
      and 84.8% (95/112) were malignant. For 112 procedures we observed a steep
      learning curve with a diagnostic yield of 80% and 87.5% for the first 30 and last
      30 procedures, respectively. The diagnostic yield in lesions <=20mm and >20mm in
      diameter was 75.6% and 89.6% (p=0.06), respectively. No significant difference in
      diagnostic yield was seen depending on lung function, and the localization of the
      lesions. Two cases (1.8%) of pneumothorax were seen during and up to 24h after
      bronchoscopy, none of them required a chest tube. CONCLUSION: Diagnostic yield
      increased with experience but was independent from the size of the lesion, the
      localisation in the lungs, and lung function. The diagnostic yield of ENB can be
      as high as for CT-guided transthoracic biopsies but carries a significantly lower
      complication rate.

PMID- 22391438
TI  - The posterior transpedicular approach for circumferential decompression and
      instrumented stabilization with titanium cage vertebrectomy reconstruction for
      spinal tumors: consecutive case series of 50 patients.
AB  - STUDY DESIGN: A retrospective case series. OBJECTIVE: To demonstrate the
      feasibility, safety, and results of the posterior transpedicular approach for
      circumferential decompression and instrumented reconstruction of thoracolumbar
      spinal tumors. SUMMARY OF BACKGROUND DATA: Patients presenting with spinal tumor
      disease requiring 3-column instrumented stabilization are typically treated with
      a combined anterior and posterior surgical approach. However, circumferential
      decompression and instrumented stabilization may also be achieved through a
      single-stage, midline posterior transpedicular approach. METHODS: Fifty
      consecutive patients (27 women and 23 men) underwent surgery between 2003 and
      2010 at a single institution by the senior author. Mean age was 55.9 years
      (range, 25-79 yr).Single or multilevel, contiguous subtotal vertebrectomy was
      performed ranging from T1 to L4 (38 thoracic and 12 lumbar). Three-column spinal
      stabilization was achieved using posterior pedicle screw fixation and vertebral
      body reconstruction, with a titanium cage introduced through the posterior
      transpedicular route. The mean follow-up period was 17 months (range, 1-54 mo).
      RESULTS: The mean operating time was 4.2 hours. The mean estimated blood loss for
      a subgroup of 9 patients with hypervascular tumor pathology was 3933 mL (range,
      2700-5800 mL). The mean blood loss in the remaining 41 patients was 1262 mL
      (range, 250-2500 mL).Postoperative neurological status was maintained or improved
      in all patients. Mean postoperative stay was 7.7 days (range, 3-12 d). At last
      review, 14 patients were alive, with a mean survival of 36 months (range, 13-71
      mo). The mean survival for the 36 patients who died was 19 months (range, 2 weeks
      to 54 mo). CONCLUSION: This is the largest reported series of patients with
      spinal tumor disease undergoing circumferential decompression and 3-column
      instrumented stabilization through the posterior transpedicular approach.This
      surgical approach provides sufficient access for safe and effective
      circumferential decompression and stabilization, with reduced complications
      compared with costotransversectomy or combined anterior transcavitary and
      posterior approaches.

PMID- 22391439
TI  - The influence of closing-opening wedge osteotomy on sagittal balance in
      thoracolumbar kyphosis secondary to ankylosing spondylitis: a comparison with
      closing wedge osteotomy.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To compare the radiographical and
      clinical outcomes between closing wedge osteotomy (CWO) and closing-opening wedge
      osteotomy (COWO) for thoracolumbar kyphosis secondary to ankylosing spondylitis.
      SUMMARY OF BACKGROUND DATA: Several surgical techniques have been used to correct
      the fixed thoracolumbar kyphosis caused by ankylosing spondylitis. To date, the
      comparison of the outcomes between CWO and COWO has not yet been addressed.
      METHODS: According to the association with anterior edge opening or not shown on
      the postoperative radiographs, 64 patients were divided into 2 groups (35
      patients in the CWO group and 29 patients in the COWO group). The radiographical
      and clinical outcomes were compared between the 2 groups, with a mean follow-up
      of 36 months (range, 24-84 mo). Radiographical measurements included thoracic
      kyphosis, lumbar lordosis, global kyphosis, sagittal vertical axis, osteotomized
      vertebra angle, and the height of the osteotomized vertebra. Oswestry Disability
      Index was evaluated at the final follow-up. RESULTS: Thoracic kyphosis did not
      change significantly between postoperatively and the final follow-up in both
      groups. The mean corrections of lumbar lordosis, global kyphosis, sagittal
      vertical axis, and osteotomized vertebra angle were significantly larger in the
      COWO group than in the CWO group (P < 0.05). Notably, statistically significant
      differences (P < 0.05) were observed in the variation of height of the
      osteotomized vertebra (1.3 cm in the CWO group vs. 0.7 cm in the COWO group). In
      both groups, no patients had pseudarthrosis at the osteotomy level at the last
      follow-up. There was no significant difference of Oswestry Disability Index
      scores between the 2 groups at the final follow-up. CONCLUSION: Both CWO and COWO
      are safe and effective surgical methods for correction of thoracolumbar kyphosis.
      COWO can obtain larger correction and better sagittal alignment without
      additional neurological complications.

PMID- 22391441
TI  - Biomechanical analysis of the intact and destabilized sheep cervical spine.
AB  - STUDY DESIGN: An in vitro investigation of the biomechanics of the intact and
      destabilized sheep cervical spine. OBJECTIVE: To establish the primary and
      coupled behaviors of the sheep cervical spine, levels C2-C7. SUMMARY OF
      BACKGROUND DATA: Sheep spine models are often used as a precursor to human
      cadaveric and clinical trials. Several studies have focused on the sheep anatomy
      and functional spinal unit biomechanics. However, there has not been a
      comprehensive study of the multilevel sheep cervical spine. METHODS: Adult sheep
      cervical spines (C2-C7) were tested in flexion-extension, lateral bending, and
      axial rotation, using a 6-df testing apparatus. Moment-rotation curves were
      generated to understand the entire loading curve. Functional spinal units were
      tested at various levels of destabilization by sequentially removing the
      stabilizing structures (i.e., ligaments, facets). RESULTS: The range of motion
      increased with caudal progression. The average total range of motion was
      approximately 77 degrees , 130 degrees , and 64 degrees  for flexion-extension,
      lateral bending, and axial rotation, respectively. The neutral zone accounted for
      a large range of motion during flexion-extension (~63%) and lateral bending
      (~72%). The flexion, extension, and axial rotation motion greatly increased after
      the removal of the capsular ligaments and facets. The C2-C3 has the largest
      change in motion during the various stages of destabilization. CONCLUSION: The
      sheep cervical spine is extremely flexible, as seen by the large range of motion
      and neutral zone. The large neutral zone may account for the coupled motion
      between axial rotation and lateral bending. The facets and capsular ligaments
      provide significant stability, especially in axial rotation, flexion, and
      extension.

PMID- 22391440
TI  - Different curve pattern and other radiographical characteristics in male and
      female patients with adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Retrospective radiographical study. OBJECTIVE: To compare the sex
      differences in curve patterns and radiographical characteristics in patients who
      have adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Sex
      differences in AIS have been documented in the incidence of curve progression,
      response to bracing, and outcomes of surgical treatment. However, limited
      information is available about the relation between sex and scoliosis curve
      patterns and radiographical presentations. METHODS: A total of 359 male and 999
      female patients with AIS with major curve of 20 degrees  or more were recruited.
      Standard posteroanterior and lateral radiographs of spine were reviewed to
      classify scoliosis curve patterns as typical or atypical and to measure curve
      severity and thoracic kyphosis. In 351 surgically treated patients, side-bending
      films were used to assess curve flexibility. Comparisons between male and female
      patients were made by subgrouping patients according to curve patterns and
      severity. RESULTS: Atypical curves were more frequently observed in male (19.8%)
      than in female patients (8.9%) (P < 0.01). Sex differences were also found in the
      distribution of curve types. Main thoracic curve was the most common curve type
      in both sexes. Furthermore, significantly higher incidence of main thoracic curve
      in patients with severe AIS than in patients with moderate AIS was found in male
      (P < 0.001) but not in female patients. In patients with severe AIS who had
      typical curve patterns that included a major thoracic curve, male patients had
      larger magnitude of thoracic curve, more severe thoracic kyphosis, and more rigid
      thoracic and lumbar curves than female patients. CONCLUSION: Atypical curve
      patterns were more predominant in male than in female patients with AIS. The
      thoracic curve in male patients with AIS might have higher incidence of
      progression than that in female patients. The higher rigidity of both thoracic
      and lumbar curves in male patients with AIS with severe curves might contribute
      to the lower curve correction rate and poor response to brace than in female
      cases.

PMID- 22391442
TI  - In vivo dynamic compressive stresses in the disc annulus: a pilot study of
      bilateral differences due to hemiepiphyseal implant in a quadruped model.
AB  - STUDY DESIGN: In vivo biomechanical study in quadruped model. OBJECTIVE: To
      develop in vivo model capable of determining physiological compressive stresses
      bilaterally in the intervertebral disc annulus and preliminarily assess effects
      of a hemiepiphyseal implant. SUMMARY OF BACKGROUND DATA: Spine growth
      modification alters stress distributions in vertebral growth plates and discs.
      Quantification of stresses is required to help assess implant efficacy and disc
      health. More generally, despite widespread and necessary use of animals in
      preclinical studies of spine instrumentation, limited quantitative information is
      available on mechanobiological conditions in quadruped spines for comparisons
      with those of humans. METHODS: Skeletally immature domestic pigs were
      instrumented with an implant and 4 stress sensors. Sensors were inserted into
      left and right sides of the annulus at 2 thoracic levels. A titanium staple-screw
      construct was implanted at 1 level. Signals were acquired intraoperatively,
      postoperatively during normal activities, and biweekly with the animal under
      anesthesia, for up to 8 weeks. RESULTS: Stresses varied by sensor location
      relative to implant, postoperative time, activity, and animal. Intraoperatively,
      the mean peak stress due to staple insertion was 1.6 MPa at the sensor nearest
      the staple. Mean stress at the end of surgery was 0.23 MPa. Mean stress standing
      the first day was 0.38 MPa. Dynamic stresses were recorded at all locations,
      including the location nearest the staple. Highest mean stresses were those
      nearest the implant. With the animal under anesthesia, the dynamic stress range
      in the resting prone position was 0.1 MPa, whereas this range was 0.9 MPa when
      the spine was manually flexed. CONCLUSION: Compressive stresses were dynamic at
      both control and stapled levels, which indicated that the disc was not
      immobilized by the implant. These pilot results suggested that mean disc
      compression was increased within the first postoperative week. Stresses ranged up
      to levels measured in humans.

PMID- 22391443
TI  - Modulation of in vitro microenvironment facilitates synovium-derived stem cell
      based nucleus pulposus tissue regeneration.
AB  - STUDY DESIGN: Two experiments were conducted. Experiment 1 evaluated the effect
      of 3 kinds of decellularized extracellular matrices (DECMs) deposited by synovium
      derived stem cells (SDSCs) and/or nucleus pulposus cells (NPCs) on SDSC expansion
      and NP lineage differentiation. Experiment 2 evaluated the effect of DECM
      deposited by SDSCs on NPC expansion and redifferentiation capacity. In both
      experiments, hypoxia was evaluated in DECM preparation and pellet culture.
      OBJECTIVE: Modulating the in vitro microenvironment facilitates SDSC-based NP
      tissue regeneration. SUMMARY OF BACKGROUND DATA: Autologous cell therapy is a
      promising approach for NP regeneration. Current in vitro expansion in monolayer
      results in cell dedifferentiation. METHODS: In Experiment 1, passage 3 SDSCs were
      expanded for 1 passage on DECM deposited by NPCs, SDSCs, or NPCs combined with
      SDSCs (50:50); DECM was prepared under either normoxia (21% O2) or hypoxia (5%
      O2). Expanded SDSCs were then cultured in a serum-free chondrogenic medium in
      hypoxia for 14 days. In Experiment 2, passage 2 NPCs were expanded for 1 passage
      on DECM deposited by SDSCs; DECM was prepared under either normoxia or hypoxia.
      Expanded NPCs were cultured in a serum-free chondrogenic medium under either
      hypoxia or normoxia for 14 days. Cell expansion on plastic flasks served as a
      control in both experiments. Fourteen-day pellets were evaluated for
      chondrogenesis using histology, immunostaining, biochemistry, and real-time
      polymerase chain reaction. RESULTS: DECM deposited by NPCs combined with SDSCs
      effectively enhanced expanded SDSC viability and guided SDSC differentiation
      toward an NP lineage; this effect is comparable with DECM deposited by SDSCs but
      higher than that deposited by NPCs. DECM prepared under normoxia favored SDSC
      viability and NP lineage differentiation whereas DECM prepared under hypoxia
      benefited NPC viability and redifferentiation. Low oxygen in a pellet culture
      system enhanced NPC viability and redifferentiation. CONCLUSION: The in vitro
      microenvironment can be modulated by low oxygen and tissue-specific cell-based
      DECM to facilitate NP tissue regeneration.

PMID- 22391444
TI  - The role of FDG-PET/CT in gynaecological cancers.
AB  - There is now a growing body of evidence supporting the use of fluorodeoxyglucose
      (FDG)-positron emission tomography (PET)/computed tomography (CT) in
      gynaecological malignancies. Although this molecular imaging technique is
      becoming increasingly available, PET/CT remains an expensive imaging tool. It is
      essential to be familiar with the circumstances in which FDG-PET/CT can add value
      and contribute to patient management and indeed to know when it is unlikely to be
      of benefit. It is also important to understand and recognize the potential
      pitfalls. FDG-PET/CT has been most widely adopted for staging patients with
      suspected advanced disease or in suspected recurrence, offering a whole-body
      imaging approach. However, there is great potential for this technique to act as
      a predictive biomarker of response to treatment, as well as a prognostic
      biomarker. In addition, FDG-PET images may now be incorporated into radiotherapy
      planning in order to refine the delineation of dose according to metabolically
      active sites of disease. This article reviews the literature that provides the
      evidence for the use of FDG-PET in gynaecological malignancies, identifies areas
      of real benefit and future potential, and highlights circumstances where there is
      limited value.

PMID- 22391445
TI  - O-GlcNAcylation of a circadian clock protein: dPER taking its sweet time.
AB  - In this issue of Genes & Development, Kim and colleagues (pp. 490-502) report
      that the Drosophila circadian repressor dPER undergoes O-linked GlcNAcylation (O
      GlcNAc). Their data show that manipulation of the relevant O-GlcNAc transferase
      (OGT) regulates behavioral rhythmicity by affecting the stability and nuclear
      translocation of dPER.

PMID- 22391447
TI  - ATRX-mediated chromatin association of histone variant macroH2A1 regulates alpha
      globin expression.
AB  - The histone variant macroH2A generally associates with transcriptionally inert
      chromatin; however, the factors that regulate its chromatin incorporation remain
      elusive. Here, we identify the SWI/SNF helicase ATRX (alpha-thalassemia/MR, X
      linked) as a novel macroH2A-interacting protein. Unlike its role in assisting
      H3.3 chromatin deposition, ATRX acts as a negative regulator of macroH2A's
      chromatin association. In human erythroleukemic cells deficient for ATRX,
      macroH2A accumulates at the HBA gene cluster on the subtelomere of chromosome 16,
      coinciding with the loss of alpha-globin expression. Collectively, our results
      implicate deregulation of macroH2A's distribution as a contributing factor to the
      alpha-thalassemia phenotype of ATRX syndrome.

PMID- 22391446
TI  - On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1.
AB  - Cellular stress responses are mediated through a series of regulatory processes
      that occur at the genomic, transcriptional, post-transcriptional, translational,
      and post-translational levels. These responses require a complex network of
      sensors and effectors from multiple signaling pathways, including the abundant
      and ubiquitous nuclear enzyme poly(ADP-ribose) (PAR) polymerase-1 (PARP-1). PARP
      1 functions at the center of cellular stress responses, where it processes
      diverse signals and, in response, directs cells to specific fates (e.g., DNA
      repair vs. cell death) based on the type and strength of the stress stimulus.
      Many of PARP-1's functions in stress response pathways are mediated by its
      regulated synthesis of PAR, a negatively charged polymer, using NAD(+) as a donor
      of ADP-ribose units. Thus, PARP-1's functions are intimately tied to nuclear
      NAD(+) metabolism and the broader metabolic profile of the cell. Recent studies
      in cell and animal models have highlighted the roles of PARP-1 and PAR in the
      response to a wide variety of extrinsic and intrinsic stress signals, including
      those initiated by oxidative, nitrosative, genotoxic, oncogenic, thermal,
      inflammatory, and metabolic stresses. These responses underlie pathological
      conditions, including cancer, inflammation-related diseases, and metabolic
      dysregulation. The development of PARP inhibitors is being pursued as a
      therapeutic approach to these conditions. In this review, we highlight the newest
      findings about PARP-1's role in stress responses in the context of the historical
      data.

PMID- 22391448
TI  - EZH2 couples pancreatic regeneration to neoplastic progression.
AB  - Although the polycomb group protein Enhancer of Zeste Homolog 2 (EZH2) is well
      recognized for its role as a key regulator of cell differentiation, its
      involvement in tissue regeneration is largely unknown. Here we show that EZH2 is
      up-regulated following cerulein-induced pancreatic injury and is required for
      tissue repair by promoting the regenerative proliferation of progenitor cells.
      Loss of EZH2 results in impaired pancreatic regeneration and accelerates
      KRas(G12D)-driven neoplasia. Our findings implicate EZH2 in constraining
      neoplastic progression through homeostatic mechanisms that control pancreatic
      regeneration and provide insights into the documented link between chronic
      pancreatic injury and an increased risk for pancreatic cancer.

PMID- 22391449
TI  - AMD1 is essential for ESC self-renewal and is translationally down-regulated on
      differentiation to neural precursor cells.
AB  - The gene expression networks governing embryonic stem cell (ESC) pluripotency are
      complex and finely regulated during differentiation toward specific lineages. We
      describe a new role for Amd1 (adenosyl methionine decarboxylase), a key enzyme in
      the polyamine synthesis pathway, in regulating both ESC self-renewal and
      differentiation to the neural lineage. Amd1 is highly expressed in ESCs and is
      translationally down-regulated by the neural precursor cell (NPC)-enriched
      microRNA miR-762 during NPC differentiation. Overexpression of Amd1 or addition
      of the polyamine spermine blocks ESC-to-NPC conversion, suggesting Amd1 must be
      down-regulated to decrease the levels of inhibitory spermine during
      differentiation. In addition, we demonstrate that high levels of Amd1 are
      required for maintenance of the ESC state. We show that forced overexpression of
      Amd1 in ESCs results in maintenance of high Myc levels and a delay in
      differentiation on removal of LIF. We propose that Amd1 is a major regulator of
      ESC self-renewal and that its essential role lies in its regulation of Myc levels
      within the cell.

PMID- 22391450
TI  - The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene
      expression.
AB  - Cell cycle progression is dependent on two major waves of gene expression. Early
      cell cycle gene expression occurs during G1/S to generate factors required for
      DNA replication, while late cell cycle gene expression begins during G2 to
      prepare for mitosis. Here we demonstrate that the MuvB complex-comprised of LIN9,
      LIN37, LIN52, LIN54, and RBBP4-serves an essential role in three distinct
      transcription complexes to regulate cell cycle gene expression. The MuvB complex,
      together with the Rb-like protein p130, E2F4, and DP1, forms the DREAM complex
      during quiescence and represses expression of both early and late genes. Upon
      cell cycle entry, the MuvB complex dissociates from p130/DREAM, binds to B-Myb,
      and reassociates with the promoters of late genes during S phase. MuvB and B-Myb
      are required for the subsequent recruitment of FoxM1 to late gene promoters
      during G2. The MuvB complex remains bound to FoxM1 during peak late cell cycle
      gene expression, while B-Myb binding is lost when it undergoes phosphorylation
      dependent, proteasome-mediated degradation during late S phase. Our results
      reveal a novel role for the MuvB complex in recruiting B-Myb and FoxM1 to promote
      late cell cycle gene expression and in regulating cell cycle gene expression from
      quiescence through mitosis.

PMID- 22391451
TI  - Beyond tRNA cleavage: novel essential function for yeast tRNA splicing
      endonuclease unrelated to tRNA processing.
AB  - Pre-tRNA splicing is an essential process in all eukaryotes. In yeast and
      vertebrates, the enzyme catalyzing intron removal from pre-tRNA is a
      heterotetrameric complex (splicing endonuclease [SEN] complex). Although the SEN
      complex is conserved, the subcellular location where pre-tRNA splicing occurs is
      not. In yeast, the SEN complex is located at the cytoplasmic surface of
      mitochondria, whereas in vertebrates, pre-tRNA splicing is nuclear. We engineered
      yeast to mimic the vertebrate cell biology and demonstrate that all three steps
      of pre-tRNA splicing, as well as tRNA nuclear export and aminoacylation, occur
      efficiently when the SEN complex is nuclear. However, nuclear pre-tRNA splicing
      fails to complement growth defects of cells with defective mitochondrial-located
      splicing, suggesting that the yeast SEN complex surprisingly serves a novel and
      essential function in the cytoplasm that is unrelated to tRNA splicing. The novel
      function requires all four SEN complex subunits and the catalytic core. A subset
      of pre-rRNAs accumulates when the SEN complex is restricted to the nucleus,
      indicating that the SEN complex moonlights in rRNA processing. Thus, findings
      suggest that selection for the subcellular distribution of the SEN complex may
      reside not in its canonical, but rather in a novel, activity.

PMID- 22391452
TI  - Paracrine effects of mesenchymal stem cells enhance vascular regeneration in
      ischemic murine skin.
AB  - New theories on the regeneration of ischemic vasculature have emerged indicating
      a pivotal role of adult stem cells. The aim of this study was to investigate
      homing and hemodynamic effects of circulating bone marrow-derived mesenchymal
      stem cells (MSCs) in a critically ischemic murine skin flap model. Bone marrow
      derived mesenchymal stem cells (Lin(-)CD105(+)) were harvested from GFP(+)-donor
      mice and transferred to wildtype C57BL/6 mice. Animals receiving GFP(+)
      fibroblasts served as a control group. Laser scanning confocal microscopy and
      intravital fluorescence microscopy were used for morphological analysis,
      monitoring and quantitative assessment of the stem cell homing and
      microhemodynamics over two weeks. Immunohistochemical staining was performed for
      GFP, eNOS, iNOS, VEGF. Tissue viability was analyzed by TUNEL-assay. We were able
      to visualize perivascular homing of MSCs in vivo. After 4 days, MSCs aligned
      along the vascular wall without undergoing endothelial or smooth muscle cell
      differentiation during the observation period. The gradual increase in arterial
      vascular resistance observed in the control group was abolished after MSC
      administration (P<0.01). At capillary level, a strong angiogenic response was
      found from day 7 onwards. Functional capillary density was raised in the MSC
      group to 197% compared to 132% in the control group (P<0.01). Paracrine
      expression of VEGF and iNOS, but not eNOS could be shown in the MSC group but not
      in the controls. In conclusion, we demonstrated that circulating bone marrow
      derived MSCs home to perivascular sites in critically ischemic tissue, exhibits
      paracrine function and augment microhemodynamics. These effects were mediated
      through arteriogenesis and angiogenesis, which contributed to vascular
      regeneration.

PMID- 22391453
TI  - Molecular imaging of cytochrome P450 activity in mice.
AB  - Detailed knowledge of drug metabolism is relevant information provided by
      preclinical drug development research. Oxidative enzymes such as those belonging
      to P450 family of cytochromes (CYP) play a prominent role in drug metabolism.
      Here, we propose an innovative method based on bioluminescence in vivo imaging
      which has the potential to simplify the in vivo measurement of CYP activity also
      providing a dynamic measure of the effects of a drug on a specific P450 enzyme
      complex in a living mouse. The method is based on a pro-luciferin which can be
      converted into the active luciferase substrate by a specific P450 activity. The
      pro-luciferin is administered to a luciferase reporter mouse which produces
      luminescent signals in relation to the cytochrome activity present in each
      tissue. The photon emission generated can be easily localized and quantified by
      optical imaging. To demonstrate the validity of the system, we pharmacologically
      induced hepatic Cyp3a in the reporter mouse and proved that pro-luciferin
      administration generates a Cyp3a selective signal in the chest area that can be
      efficiently detected by optical imaging. The kind of tool generated has the
      potential to be exploited for the study of additional CYPs.

PMID- 22391454
TI  - Minimal access maximal success; a myth or a reality.
AB  - Minimal invasive surgery is one of the most challenging advances in the craft of
      surgery in last 2 decades. In our country the advanced craft has been in practice
      for more than one and a half decade and some of our committed surgeons have
      mastered this craft and made an impact not only on national level but also on
      international level. Many times we may get impressed by watching the masters in
      the craft but forgetting the efforts the master has put in to reach the Zenith
      and in a bid to imitate the master we may ignore the awaiting disaster. In this
      article I will be discussing the overall impact of this surgical craft globally
      and its various evidence based pros and cons with a particular reference to
      colorectal surgery to ascertain whether the craft of minimal access with maximal
      success is a myth or a reality.

PMID- 22391455
TI  - Proteinuria as a surrogate end point--more data are needed.
AB  - Surrogate end points have the potential to facilitate drug development because
      effects on surrogate end points can sometimes be demonstrated more rapidly and in
      smaller studies than can effects on clinical outcomes of interest. Proteinuria
      has been repeatedly proposed as a surrogate end point for renal outcomes in drug
      development; however, the FDA has generally not accepted effects on proteinuria
      as evidence of a drug's effectiveness. Proteinuria is an early marker of some
      kidney diseases and increases in proteinuria can predict risk of disease
      progression. Whether or not treatment effects on proteinuria can reliably predict
      treatment effects on renal outcomes is not known. Nevertheless, it may be
      reasonable to use effects on proteinuria as a basis for accelerated approval of a
      drug if certain conditions are met. Approval under this pathway carries with it a
      requirement to complete a study after drug approval that verifies the anticipated
      treatment benefit.

PMID- 22391457
TI  - Fullerene hollow microspheres prepared by bubble-templates as sensitive and
      selective electrocatalytic sensor for biomolecules.
AB  - We developed an electrocatalytic sensor based on C(60) hollow microspheres for
      highly sensitive and selective detection of dopamine (DA) in the presence of
      ascorbic acid (AA), and uric acid (UA) in the presence of l-cysteine (RSH). The
      hollow microspheres of C(60) with a diameter controllable in the range of 0.5 to
      1.5 MUm and a thickness of 200 nm are synthesized by a high-temperature
      reprecipitation method with the assistance of alcohol bubbles. The
      superhydrophobicity of C(60) hollow microspheres makes them capable of forming a
      compact thin film at air/water interface, which can be readily transferred on the
      surface of gold or glassy carbon electrodes. This porous C(60) film made from
      C(60) hollow microspheres shows a specific surface area as high as 107 m(2) g(
      1). In order to obtain a conducting film, the C(60)-modified electrode is
      pretreated by scanning the potential range from 0.0 to -1.5 V in 1 M KOH followed
      by potential cycling between 550 to -50 mV in a pH 7.2 phosphate buffer solution.
      On the basis of XPS and IR measurements, we found that surface oxides, such as 
      OH and C?O groups, are introduced on the surfaces of the conducting C(60) film.
      This, combined with the porosity that enhances the adsorption activity of C(60)
      modified electrodes, enable the electrocatalytic analysis of target biomolecules
      with detection limit as low as 0.1 nM for DA in the presence of AA, and 1 MUM for
      UA in the presence of RSH.

PMID- 22391456
TI  - Proteinuria should be used as a surrogate in CKD.
AB  - Surrogate end points of renal failure are instrumental to the testing of new
      treatments in patients with chronic kidney disease, the natural history of which
      is characterized by a slow, asymptomatic decline in renal function. The magnitude
      of proteinuria is widely recognized as a marker of the severity of
      glomerulopathy. Population-based studies have identified proteinuria as a
      predictor of future decline in glomerular filtration rate and of the development
      of end-stage renal disease. More importantly, a reduction in proteinuria
      invariably translates into a protection from renal function decline in patients
      with diabetic and nondiabetic renal disease with overt proteinuria. Thus,
      proteinuria should be considered a valuable surrogate end point for clinical
      trials in patients with proteinuric renal diseases.

PMID- 22391458
TI  - Instabilities of the resting state in a mathematical model of calcium handling in
      cardiac myocytes.
AB  - We analyze a recently published model of calcium handling in cardiac myocytes in
      order to find conditions for the presence of instabilities in the resting state
      of the model. Such instabilities can create calcium waves which in turn may be
      able to initiate cardiac arrhythmias. The model was developed by Swietach,
      Spitzer and Vaughan-Jones in order to study the effect, on calcium waves, of
      varying ryanodine receptor (RyR)-permeability, sarco/endoplasmic reticulum
      calcium ATPase (SERCA) and calcium diffusion. We study the model using the
      extracellular calcium concentration c(e) and the maximal velocity of the SERCA
      pump v(SERCA) as control parameters. In the (c(e),v(SERCA))-domain we derive an
      explicit function v*=v*(c(e)), and we claim that any resting state based on
      parameters that lie above the curve (i.e. any pair (c(e),v(SERCA)) such that with
      v(SERCA) > v*(c(e))) is unstable in the sense that small perturbations will grow
      and can eventually turn into a calcium wave. And conversely; any pair
      (c(e),v(SERCA)) below the curve is stable in the sense that small perturbations
      to the resting state will decay to rest. This claim is supported by analyzing the
      stability of the system in terms of computing the eigenmodes of the linearized
      model. Furthermore, the claim is supported by direct simulations based on the non
      linear model. Since the curve separating stable from unstable states is given as
      an explicit function, we can show how stability depends on other parameters of
      the model.

PMID- 22391459
TI  - Exploiting multi-layered information to iteratively predict protein functions.
AB  - BACKGROUND: Similarity based computational methods are a useful tool for
      predicting protein functions from protein-protein interaction (PPI) datasets.
      Although various similarity-based prediction algorithms have been proposed,
      unsatisfactory prediction results have occurred on many occasions. The purpose of
      this type of algorithm is to predict functions of an unannotated protein from the
      functions of those proteins that are similar to the unannotated protein.
      Therefore, the prediction quality largely depends on how to select a set of
      proper proteins (i.e., a prediction domain) from which the functions of an
      unannotated protein are predicted, and how to measure the similarity between
      proteins. Another issue with existing algorithms is they only believe the
      function prediction is a one-off procedure, ignoring the fact that interactions
      amongst proteins are mutual and dynamic in terms of similarity when predicting
      functions. How to resolve these major issues to increase prediction quality
      remains a challenge in computational biology. RESULTS: In this paper, we propose
      an innovative approach to predict protein functions of unannotated proteins
      iteratively from a PPI dataset. The iterative approach takes into account the
      mutual and dynamic features of protein interactions when predicting functions,
      and addresses the issues of protein similarity measurement and prediction domain
      selection by introducing into the prediction algorithm a new semantic protein
      similarity and a method of selecting the multi-layer prediction domain. The new
      protein similarity is based on the multi-layered information carried by protein
      functions. The evaluations conducted on real protein interaction datasets
      demonstrated that the proposed iterative function prediction method outperformed
      other similar or non-iterative methods, and provided better prediction results.
      CONCLUSIONS: The new protein similarity derived from multi-layered information of
      protein functions more reasonably reflects the intrinsic relationships among
      proteins, and significant improvement to the prediction quality can occur through
      incorporation of mutual and dynamic features of protein interactions into the
      prediction algorithm.

PMID- 22391460
TI  - EDL-291, a novel isoquinoline, presents antiglioblastoma effects in vitro and in
      vivo.
AB  - To investigate the effectiveness of EDL-291, a 6,7-dimethoxy-1-[4-(4
      methoxypyridin-3-yl)benzyl]-1,2,3,4-tetrahydroisoquinoline dihydrochloride
      compound, in inhibiting the survival of glioblastoma in vitro and in vivo. Dose
      response curves were generated to determine the EC50 in rat and human
      glioblastoma cell lines by treatment with different dilutions of EDL-291. To
      evaluate the architecture of the glioblastoma cells after treatment with EDL-291,
      the rat and human glioblastoma cells were stained with Mito Tracker Green FM. To
      determine whether autophagy was induced in EDL-291-treated glioblastoma cells,
      both rat and human glioblastoma cell lines were stained with acridine orange and
      light chain-3 immunoblots were performed. The efficacy of EDL-291 was monitored
      in vivo using a rat glioblastoma model. Rat glioblastoma cells were transplanted
      into an intracranial rat model, followed by infusions of saline, a low dose of
      EDL-291 (20 mg/kg for the first half hour, followed by 40 mg/kg EDL-291 in saline
      for 4 h), or a high dose of EDL-291 (60 mg/kg for the first half hour, followed
      by 90 mg/kg EDL-291 for 4 h). EDL-291 inhibits glioblastoma in vitro by
      destroying the mitochondria as shown with Mito Tracker Green FM. Acridine orange
      staining and light chain-3 immunoblots suggest that autophagy is induced when
      glioblastoma cells are treated with EDL-291. In vivo, a low dosage of EDL-291 is
      sufficient and effective in reducing glioblastoma tumor size. EDL-291 selectively
      induces cell death in rat and human glioblastoma cell lines by the induction of
      autophagy. EDL-291 exhibits antiglioblastoma effects both in vitro and in vivo.

PMID- 22391461
TI  - Influence of different soluble dietary fibers on the bioaccessibility of the
      minor Fusarium mycotoxin beauvericin.
AB  - Beauvericin (BEA) is a bioactive compound produced by the secondary metabolism of
      several Fusarium strains and is known to have various biological activities. This
      study investigated the bioaccessibility of the BEA tested in concentrations of 5
      and 25mg/L, in a model solution and in wheat crispy breads elaborated with
      different natural binding compounds as the soluble alimentary dietary fibers beta
      1,3 glucan, chitosan low molecular weight (L.M.W.), chitosan medium molecular
      weight (M.M.W.), fructooligosaccharides (FOS), galattomannan, inulin and pectin,
      added at concentrations of 1% and 5%. The bioaccessibility was determinated by
      employing a simulated gastrointestinal digestion that simulates the physiologic
      conditions of the digestive tract until the colonic compartment. The
      determination of BEA in the intestinal fluids was carried out by liquid
      chromatography-mass spectrometry detection (LC-MS). The mean BEA bioaccessibility
      data in the model solutions ranged from 31.8% of the samples treated with only
      the duodenal digestion until 54.0% of the samples processed including the colonic
      fermentation, whereas in the alimentary system composed by the wheat crispy
      breads produced with different fiber concentration the duodenal and the
      duodenal+colonic BEA bioaccessibility resulted in 1.9% and 27.0% respectively.

PMID- 22391462
TI  - p-Methoxyl-diphenyl diselenide protects against cisplatin-induced renal toxicity
      in mice.
AB  - The present study was designed to investigate the effects of p-methoxyl-diphenyl
      diselenide (OMePhSe)(2) on oxidative stress and renal damage parameters of mice
      exposed to cisplatin. (OMePhSe)(2) (50 and 100 mg/kg/day) was orally administered
      to mice for six consecutive days. On the third day after the beginning of
      (OMePhSe)(2) treatment, the renal toxicity was induced by injecting cisplatin (10
      mg/kg intraperitoneal) in mice. (OMePhSe)(2) treatment (50 mg/kg) partially
      reduced plasma urea and creatinine levels increased by cisplatin.
      Histopathological examination of kidneys showed that (OMePhSe)(2) ameliorated
      renal injury caused by cisplatin. (OMePhSe)(2) attenuated the decrease in reduced
      glutathione (GSH) and ascorbic acid (AA) levels, the inhibition of glutathione
      peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and
      catalase (CAT) activities caused by cisplatin in kidney. (OMePhSe)(2) treatment
      partially protected against the inhibition of renal delta-aminolevulinic
      dehydratase (delta-ALA-D) activity caused by cisplatin. No alteration in renal
      lipid peroxidation levels was found in cisplatin and/or (OMePhSe)(2) groups.
      (OMePhSe)(2) was effective against the increase in reactive species (RS) levels
      caused by the cisplatin exposure. Based on the renoprotective and antioxidant
      actions of (OMePhSe)(2) we suggest that this organoselenium compound could be
      considered a feasible candidate to protect against toxicity commonly encountered
      in cisplatin exposure.

PMID- 22391463
TI  - Collaborative evaluation of a high school prevention curriculum: How methods of
      collaborative evaluation enhanced a randomized control trial to inform program
      improvement.
AB  - Blending high-quality and rigorous research with pure evaluation practice can
      often be best accomplished through thoughtful collaboration. The evaluation of a
      high school drug prevention program (All Stars Senior) is an example of how
      perceived competing purposes and methodologies can coexist to investigate
      formative and summative outcome variables that can be used for program
      improvement. Throughout this project there were many examples of client learning
      from evaluator and evaluator learning from client. This article presents
      convincing evidence that collaborative evaluation can improve the design,
      implementation, and findings of the randomized control trial. Throughout this
      paper, we discuss many examples of good science, good evaluation, and other
      practical benefits of practicing collaborative evaluation. Ultimately, the
      authors created the term pre-formative evaluation to describe the period prior to
      data collection and before program implementation, when collaborative evaluation
      can inform program improvement.

PMID- 22391464
TI  - Successful treatment of cutaneous zygomycosis with extensive surgical debridement
      and oral posaconazole in an immunocompetent patient.
AB  - We describe a case of successful treatment of cutaneous zygomycosis using a
      combination of extensive surgical debridement and the oral antifungal agent,
      posaconazole.

PMID- 22391465
TI  - Closure of palatal fistula with local double-breasted mucoperiosteal flaps.
AB  - INTRODUCTION AND OBJECTIVES: Despite improvement to surgical techniques of cleft
      palate surgery, palatal fistulas remain a challenge. Many surgical procedures
      have been described for repair of these fistulas either by using the local tissue
      or by importing a new tissue from adjacent areas. In this report, we describe our
      technique for closure of palatal fistula using double-breasted mucoperiosteal
      flaps based on the greater palatine artery. PATIENTS AND METHODS: Eight patients
      with oronasal fistulas located in the posterior two-thirds of the hard palate
      following cleft-palate repair were treated by double-breasted mucoperiosteal
      flaps with an overlapping zone of 1-2 cm. RESULTS: All fistulas successively
      healed, none of our patients developed any significant postoperative bleeding,
      infection or fistula recurrence. CONCLUSIONS: Double breasated mucoperiostial
      flap is a simple successful option for correction of oronasal fistula.

PMID- 22391466
TI  - Barking seizure: acute episodes of barking in a 75-year-old previously healthy
      man.
AB  - A 75-year-old right-handed man was admitted to our emergency department
      complaining of recurrent episodes of involuntary 'barking' within the past 12h.
      The episodes had occurred after an initial two-minute attack from sleep involving
      tonic contraction of the upper extremities and jaw locking. By the time of
      admission, the patient had had a total of at least 7-10 'barking' episodes, each
      lasting 30-45 s. Seven months prior to his current admission, the patient had had
      a minor ischemic stroke causing mild left paresis, which had resolved completely.
      His awake EEG revealed a normal background pattern interrupted by runs of two per
      second slow waves mixed with low-voltage spikes in the left temporal lobe with a
      left mid-temporal emphasis. The patient was diagnosed with recurrent simple
      partial seizures, and treatment with intravenous valproic acid was initiated. He
      was discharged four days later without having experienced any further barking
      episodes. Atypical presentations of the epileptic seizures have been described in
      the literature, but ictal barking is very rare manifestation of epilepsy.

PMID- 22391467
TI  - The low permeability of healthy meniscus and labrum limit articular cartilage
      consolidation and maintain fluid load support in the knee and hip.
AB  - The knee meniscus and hip labrum appear to be important for joint health, but the
      mechanisms by which these structures perform their functions are not fully
      understood. The fluid phase of articular cartilage provides compressive stiffness
      and aids in maintaining a low friction articulation. Healthy fibrocartilage, the
      tissue of meniscus and labrum, has a lower fluid permeability than articular
      cartilage. In this study we hypothesized that an important function of the knee
      meniscus and the hip labrum is to augment fluid retention in the articular
      cartilage of a mechanically loaded joint. Axisymmetric hyperporoelastic finite
      element models were analyzed for an idealized knee and an idealized hip. The
      results indicate that the meniscus maintained fluid pressure and inhibited fluid
      exudation in knee articular cartilage. Similar, but smaller, effects were seen
      with the labrum in the hip. Increasing the fibrocartilage permeability relative
      to that of articular cartilage gave a consolidation rate and loss of fluid load
      support comparable to that predicted by meniscectomy or labrectomy. The reduced
      articular cartilage fluid pressure that was calculated for the joint periphery is
      consistent with patterns of endochondral ossification and osteophyte formation in
      knee and hip osteoarthritis. High articular central strains and loss of fluid
      load support after meniscectomy could lead to fibrillation. An intact low
      permeability fibrocartilage is important for limiting fluid exudation from
      articular cartilage in the hip and knee. This may be an important aspect of the
      role of fibrocartilage in protecting these joints from osteoarthritis.

PMID- 22391468
TI  - Urogenital manifestations in Wegener granulomatosis: a study of 11 cases and
      review of the literature.
AB  - We describe the main characteristics and treatment of urogenital manifestations
      in patients with Wegener granulomatosis (WG). We conducted a retrospective review
      of the charts of 11 patients with WG. All patients were men, and their median age
      at WG diagnosis was 53 years (range, 21-70 yr). Urogenital involvement was
      present at onset of WG in 9 cases (81%), it was the first clinical evidence of WG
      in 2 cases (18%), and was a symptom of WG relapse in 6 cases (54%). Symptomatic
      urogenital involvement included prostatitis (n = 4) (with suspicion of an abscess
      in 1 case), orchitis (n = 4), epididymitis (n = 1), a renal pseudotumor (n = 2),
      ureteral stenosis (n = 1), and penile ulceration (n = 1). Urogenital symptoms
      rapidly resolved after therapy with glucocorticoids and immunosuppressive agents.
      Several patients underwent a surgical procedure, either at the time of diagnosis
      (n = 3) (consisting of an open nephrectomy and radical prostatectomy for
      suspicion of carcinoma, suprapubic cystostomy for acute urinary retention), or
      during follow-up (n = 3) (consisting of ureteral double J stents for ureteral
      stenosis, and prostate transurethral resection because of dysuria). After a mean
      follow-up of 56 months, urogenital relapse occurred in 4 patients (36%).
      Urogenital involvement can be the first clinical evidence of WG. Some
      presentations, such as a renal or prostate mass that mimics cancer or an abscess,
      should be assessed to avoid unnecessary radical surgery. Urogenital symptoms can
      be promptly resolved with glucocorticoids and immunosuppressive agents. However,
      surgical procedures, such as prostatic transurethral resection, may be mandatory
      in patients with persistent symptoms.

PMID- 22391469
TI  - Testicular vasculitis: findings differentiating isolated disease from systemic
      disease in 72 patients.
AB  - Testicular vasculitis (TV) may be part of systemic (testicular) vasculitis (STV)
      or may exist as single-organ/isolated (testicular) vasculitis (ITV). In the
      current study we sought to identify clinical and histologic features that
      distinguish STV from ITV. The distinction was deemed important because it is
      already well established that in other forms of single organ vasculitis, surgical
      therapy alone may be curative. We identified patients with biopsy-proven TV from
      pathology databases from our institution and from an English-language PubMed
      search. Patients were included if data were available to determine TV extent
      confidently. Data recorded included clinical, laboratory, and histologic
      features; treatment; and clinical follow-up. The study included 72 patients with
      TV (mean age, 42 yr; range, 4-78 yr) (7 from our institution). About 74% of
      patients presented with painful testicular swelling/mass, 10% with a painless
      testicular swelling/mass, and 4% with epididymal swelling/mass. Eleven percent
      had no testicular complaints and vasculitis was discovered at autopsy or in other
      surgical interventions. Vasculitis involved the testicle in 80.3% of cases, the
      epididymis in 44.6%, and the spermatic cord in 30.6%. Thirty-seven (51%) patients
      had ITV and 35 (49%) had STV. No differences between ITV and STV patients were
      found in regards to age, presenting testicular features, duration of testicular
      symptoms, and time of follow-up. Compared to ITV patients, STV patients presented
      more often with constitutional/musculoskeletal symptoms (74.3% vs. 8.3%,
      respectively; p = 0.0001), elevated erythrocyte sedimentation rate (94.7% vs.
      16%; p = 0.0001), and anemia (50% vs. 0%; p = 0.0001). Neoplasm was more
      frequently suspected in ITV than in STV (74.2% vs. 31.6%; p = 0.001), but only
      occurred in 2 ITV patients. Long-term glucocorticoid therapy was given only to
      STV patients, and 59.1% of them also received cytotoxic agents. ITV was diagnosed
      more often by orchiectomy (81.1% vs. 42.9%; p = 0.001) and less frequently by
      testicular biopsy (2.7% vs. 28.6%; p = 0.003) than STV. Nongranulomatous
      inflammation affecting medium-sized vessels occurred in most patients with both
      ITV and STV. Among STV, polyarteritis nodosa was the most frequently diagnosed
      (63%), followed by Wegener granulomatosis (17%).In summary, TV occurs as ITV in
      men usually presenting with a testicular mass in the absence of systemic symptoms
      and normal laboratory results. In most ITV patients, a testicular neoplasm is
      initially suspected, and TV is an unexpected finding. After surgical removal, ITV
      does not require systemic therapy. Polyarteritis nodosa is the systemic
      vasculitis most frequently associated with testicular involvement.

PMID- 22391470
TI  - Metastatic infectious disease and clinical outcome in Staphylococcus aureus and
      Streptococcus species bacteremia.
AB  - Early detection of metastatic infection in patients with Gram-positive bacteremia
      is important as morbidity and mortality are higher in the presence of these foci,
      probably due to incomplete eradication of clinically silent foci during initial
      treatment. We performed a prospective study in 115 patients with Staphylococcus
      aureus or Streptococcus species bacteremia with at least 1 risk factor for the
      development of metastatic foci, such as community acquisition, treatment delay,
      persistently positive blood cultures for >48 hours, and persistent fever >72
      hours after initiation of treatment. An intensive search for metastatic
      infectious foci was performed including 18F-fluorodeoxyglucose-positron emission
      tomography in combination with low-dose computed tomography scanning for
      optimizing anatomical correlation (FDG-PET/CT) and echocardiography in the first
      2 weeks of admission. Metastatic infectious foci were detected in 84 of 115 (73%)
      patients. Endocarditis (22 cases), endovascular infections (19 cases), pulmonary
      abscesses (16 cases), and spondylodiscitis (11 cases) were diagnosed most
      frequently. The incidence of metastatic infection was similar in patients with
      Streptococcus species and patients with S. aureus bacteremia. Signs and symptoms
      guiding the attending physician in the diagnostic workup were present in only a
      minority of cases (41%). An unknown portal of entry, treatment delay >48 hours,
      and the presence of foreign body material were significant risk factors for
      developing metastatic foci. Mean C-reactive protein levels on admission were
      significantly higher in patients with metastatic infectious foci (74 vs. 160
      mg/L). FDG-PET/CT was the first technique to localize metastatic infectious foci
      in 35 of 115 (30%) patients. As only a minority of foci were accompanied by
      guiding signs or symptoms, the number of foci revealed by symptom-guided CT,
      ultrasound, and magnetic resonance imaging remained low. Mortality tended to be
      lower in patients without complicated infection compared to those with metastatic
      foci (16% vs. 25%, respectively). Five of 31 patients (16%) without proven
      metastatic foci died. In retrospect, 3 of these 5 patients likely had metastatic
      foci that could not be diagnosed while alive. In patients with Gram-positive
      bacteremia and a high risk of developing complicated infection, a structured
      protocol including echocardiography and FDG-PET/CT aimed at detecting metastatic
      infectious foci can contribute to improved outcome.

PMID- 22391471
TI  - Inflammatory myopathies with anti-Ku antibodies: a prognosis dependent on
      associated lung disease.
AB  - Anti-Ku antibodies have been reported in a wide spectrum of autoimmune diseases,
      sometimes in association with inflammatory myopathies (IM). We studied the
      clinical, laboratory, and muscle histologic features of all anti-Ku-positive
      patients detected in our hospital during the last 10 years, as well as their
      treatment and outcomes. Anti-Ku antibodies were found in 34 patients (0.46% of
      20,600 sera positive for antinuclear antibodies), and complete data were
      available for 30 patients; 86.7% were female, mean age was 49 years (range, 20-73
      yr). The most frequent clinical manifestations were arthralgia (77%) and Raynaud
      phenomenon (53%). Eleven (37%) patients had IM, 8 of them as part of an overlap
      syndrome defined as IM associated with connective autoimmune disease (5 systemic
      sclerosis [SSc], 2 Sjogren syndrome (SS), and 1 systemic lupus erythematosus
      [SLE]). Of 21 patients without IM, 19 had autoimmune diseases (including 6 SLE, 2
      SSc, 2 SS, and 2 rheumatoid arthritis), 1 had bronchial neoplasia, and 1 had
      nephroangiosclerosis. Clinical features of the 9 patients with IM were myalgia
      (91%), proximal muscle weakness (89%), and dysphagia (36%). All had increased
      creatine kinase (median, 2210 U/L; range, 194-4073 U/L). Muscle biopsy showed
      necrosis, inflammation, and positive HLA class I immunostaining. Interstitial
      lung disease (ILD) was detected on computed tomography (CT) scan in 11 patients
      (37%) and was significantly more frequent in patients with IM (82% vs. 10.5%, p <
      0.001). Fourteen (47%) patients required no immunosuppressive treatment or only a
      low corticosteroid dose (<15 mg/d, n = 3). A high dose of corticosteroids was
      more frequently administered in patients with IM (10/11 cases, 80% with
      associated ILD) than in patients without IM (4/19 cases, 0 with ILD). Complete
      muscle remission after steroids occurred in 73% of patients with IM. Lung disease
      was corticoresistant in 6 of 8 (75%) treated cases.Anti-Ku antibodies remain
      rarely detected, but their presence can be frequently associated with
      corticosensitive IM and severe, corticoresistant ILD.

PMID- 22391472
TI  - Systematic use of universal 16S rRNA gene polymerase chain reaction (PCR) and
      sequencing for processing pleural effusions improves conventional culture
      techniques.
AB  - Conventional culture of pleural fluid samples frequently provides false-negative
      results. Universal polymerase chain reaction (PCR) of the 16S ribosomal
      ribonucleic acid (rRNA) gene (16S PCR) has proven useful in the diagnosis of
      various bacterial infections. We conducted a prospective study to assess the
      value of 16S PCR in the etiologic diagnosis of pleural effusion. All pleural
      fluid samples received for culture were also studied using 16S PCR. Positive
      samples were sequenced for identification. Clinical records and conventional
      culture results were analyzed to classify pleural fluid samples as infected or
      not infected. We studied 723 samples. We excluded 188 samples because they were
      obtained from a long-term chest tube, there was a diagnosis of mycobacterial
      infection, or there were insufficient data to classify the episode. Finally, 535
      pleural fluid samples were analyzed. According to our criteria, 82 (15.3%) were
      infected and 453 (84.7%) were not infected. In the infected samples, 16S PCR was
      positive in 67 samples (81.7%) while conventional culture was positive in 45
      (54.9%). There were 4 false positives with 16S PCR (0.9%) and 12 with culture
      (2.6%). The values for the etiologic diagnosis of bacterial pleural effusion of
      conventional culture compared with 16S PCR were as follows: sensitivity,
      54.9%/81.7%; specificity, 97.4%/99.1%; positive predictive value, 76.3%/94.4%;
      negative predictive value, 92.6%/96.8%; and accuracy, 90.8%/96.5%.When compared
      with conventional culture, 16S PCR plus sequencing substantially improves the
      etiologic diagnosis of infectious pleural effusion. In our opinion, this
      technique should be added to the routine diagnostic armamentarium of clinical
      microbiology laboratories.

PMID- 22391473
TI  - Bartonella henselae infections in solid organ transplant recipients: report of 5
      cases and review of the literature.
AB  - Bartonella henselae is the causative agent of cat scratch disease and bacillary
      angiomatosis-peliosis. The spectrum of disease, diagnosis, and management of B.
      henselae infection in solid organ transplant recipients has not been well
      characterized. We identified 29 cases of solid organ transplant recipients who
      had Bartonella infection, 24 by a review of the English-language literature and 5
      from our institution. Localized cat scratch disease was found in 8 patients
      (28%), and disseminated infection was found in 21 patients (72%). The mean time
      after transplantation to development of Bartonella infection among those with cat
      scratch disease was 5.6 +/- 5.3 years, and among those with disseminated
      infection was 2.7 +/- 2.4 years. Prominent clinical features included cat
      exposure in 26 patients (90%), fever in 27 patients (93%), lymphadenopathy in 12
      patients (41%), and skin lesions in 7 patients (24%). Methods used in
      establishing the diagnosis of Bartonella infection included culture, polymerase
      chain reaction (PCR) assay, serologic assays, and histopathologic examination.
      Culture was positive in 2 of only 4 patients in whom this was performed, and PCR
      was positive in 12 of 14 patients (86%) in whom this test was performed.
      Serologic assays were positive in all 23 patients who were tested.
      Histopathologic examination of tissues in all 8 patients who had cat scratch
      disease revealed granulomatous inflammation in 4 (50%) and bacillary angiomatosis
      peliosis in 2 (25%). Among the 15 patients who had disseminated infection and who
      had tissue examined, 8 (53%) had only granulomatous inflammation, 4 had only
      bacillary angiomatosis-peliosis (27%), and 2 had both granulomas and bacillary
      angiomatosis-peliosis (13%). A positive Warthin-Starry or Steiner stain was noted
      in 12 of 19 patients (63%) who had 1 of these stains performed. All 8 patients
      with cat scratch disease and 19 of 21 patients with disseminated bartonellosis
      were cured with antimicrobial therapy. Two patients, both of whom had
      endocarditis, died. Among solid organ transplant recipients, infection with B.
      henselae is uncommon and has diverse disease manifestations including
      disseminated disease. Persistent fevers or lymphadenopathy in a transplant
      recipient who has been exposed to cats should prompt clinicians to maintain a
      high index of suspicion for B. henselae infection. Identifying B. henselae as the
      causative organism often requires multiple diagnostic studies. Once the diagnosis
      is established, most solid organ transplant recipients respond appropriately to
      antimicrobial treatment.

PMID- 22391474
TI  - Light-to-electron converting panchromatic supramolecular solar cells of
      phthalocyanine-porphyrin heterodimers adsorbed onto nanocrystalline SnO2
      electrodes.
AB  - Broadband capturing supramolecular solar cells are constructed by layer-by-layer
      deposition of oppositely charged phthalocyanine and porphyrin dyes onto the
      SnO(2) surface.

PMID- 22391475
TI  - ERP correlates of spatially incongruent object identification during scene
      viewing: contextual expectancy versus simultaneous processing.
AB  - Object processing is affected by the gist of the scene within which it is
      embedded. Previous ERP research has suggested that manipulating the semantic
      congruency between an object and the surrounding scene affects the high level
      (semantic) representation of that object emerging after the presentation of the
      scene (Ganis & Kutas, 2003). In two ERP experiments, we investigated whether
      there would be a similar electrophysiological response when spatial congruency of
      an object in a scene was manipulated while the semantic congruency remained the
      same. Apart from the location of the object, all other object features were
      congruent with the scene (e.g., in a bedroom scene, either a painting or a cat
      appeared on the wall). In the first experiment, participants were shown a
      location cue and then a scene image for 300 ms, after which an object image
      appeared on the cued location for 300 ms. Spatially incongruent objects elicited
      a stronger centro-frontal N300-N400 effect in the 275-500 ms window relative to
      the spatially congruent objects. We also found early ERP effects, dominant on the
      left hemisphere electrodes. Strikingly, LORETA analysis revealed that these
      activations were mainly located in the superior and middle temporal gyrus of the
      right hemisphere. In the second experiment, we used a paradigm similar to Mudrik,
      Lamy, and Deouell (2010). The scene and the object were presented together for
      300 ms after the location cue. This time, we did not observe either an early or
      the pronounced N300-N400 effect. In contrast to Experiment 1, LORETA analysis on
      the N400 time-window revealed that the generators of these weak ERP effects were
      mainly located in the temporal lobe of the left hemisphere. Our results suggest
      that, when the scene is presented before the object, top-down spatial encoding
      processes are initiated and the right superior temporal gyrus is activated, as
      previously suggested (Ellison, Schindler, Pattison, & Milner, 2004). Mismatch
      between the actual object features and the spatially driven top-down structural
      and functional features could lead to the early effect, and then to the N300-N400
      effect. In contrast, when the scene is not presented before the object, the
      spatial encoding could not happen early and strong enough to initiate spatial
      object-integration effects. Our results indicate that spatial information is an
      early and essential part in scene-object integration, and it primes structural as
      well as semantic features of an object.

PMID- 22391476
TI  - Self-esteem modulates dorsal anterior cingulate cortical response in self
      referential processing.
AB  - Self-esteem can be defined as evaluations that individuals make about their worth
      as human beings. These evaluations are in part based on how we evaluate ourselves
      on our abilities, values, opinions, etc. compared with others or our past or
      ideal self; and they are also influenced by a thought that what others may think
      about us. Studies to date investigating the neural mechanisms underlying
      individual differences in self-esteem have focused mostly on the latter process
      (i.e. on how self-esteem is associated with neural correlates of processing
      feedback from others). However, given that people spend a lot of time thinking
      about themselves and evaluating their worth, we aimed to investigate neural
      mechanism underlying the association between levels of self-esteem and processing
      of self-relevant information. Seventeen participants completed a functional
      magnetic resonance imaging (fMRI) scan during which they were asked to evaluate
      whether a given statement is true about them (Self), an acquaintance of theirs
      (Other), or about general knowledge (Semantic). A whole brain correlational
      analysis revealed a significant negative correlation between levels of self
      esteem and changes in activation of dorsal anterior cingulate gyrus (dACC, BA32)
      in response to evaluating self-relevant information (Self versus Other contrast).
      This result extends previous findings implicating this region in the association
      between processing evaluative feedback and levels of self-esteem and suggests
      that activity in this region is affected by self-esteem levels also when
      individuals are engaged in self-referencing and self-evaluation. Future studies
      should investigate whether these associations are affected differently based on
      valence of self-evaluations.

PMID- 22391477
TI  - Phenazepam abuse in Finland: findings from apprehended drivers, post-mortem cases
      and police confiscations.
AB  - Phenazepam is a long-acting benzodiazepine that, unlike other benzodiazepines, is
      currently not scheduled as a narcotic in Finland, most other European countries
      or the USA. It is used as an anxiolytic, sedative-hypnotic and anti-epileptic,
      mainly in Russia. In Finland, as well as in some other countries, an increase in
      the unauthorized use of phenazepam has been observed in recent years. In the one
      year period between July 1, 2010 and June 30, 2011 the prevalence of phenazepam
      in Finland was assessed among drivers apprehended for driving under the influence
      of drugs (DUID), in medico-legal autopsy cases and in police confiscations of
      illicit drugs. In DUID cases an LC-MS/MS method preceded by solid phase
      extraction was used for the determination of phenazepam. In the post-mortem
      investigations the sample preparation consisted of liquid-liquid extraction
      followed by derivatization and the determination was carried out by GC-MS. The
      police confiscations were analysed by GC-MS. There were 141 positive phenazepam
      cases among apprehended drivers, representing approximately 3.5% of all confirmed
      drug cases (n=4007) in this time period. The median (range) phenazepam blood
      concentration in DUID cases was 0.061 mg/L (0.004-3.600 mg/L). The median
      phenazepam concentration in cases with no concomitant stimulant use was
      significantly higher than the overall median concentration. Phenazepam was found
      in 17 medico-legal autopsy cases and the median (range) blood concentration was
      0.048 mg/L (0.007-1.600 mg/L). Phenazepam was not considered by the medico-legal
      team to be the sole cause of death in any of the cases, the majority of them
      being accidental opiod overdoses. There were 26 seizures of phenazepam by the
      Police in the time period studied, some of the batches consisted of a mixture of
      phenazepam and stimulant designer drugs. The data show that phenazepam abuse is a
      widespread phenomenon in Finland. A typical user was a male multi-drug user in
      his 30s. The concentration range of phenazepam among apprehended drivers and
      medico-legal autopsy cases was wide and the drug was usually found along with
      other psychoactive drugs. Therefore, although it seems likely that phenazepam
      contributed to impairment of driving in some DUID cases, the extent of its effect
      remains unclear and further studies are needed to define the concentrations
      causing impairment and toxicity.

PMID- 22391478
TI  - Mucinous tubular and spindle cell carcinoma of the kidney: imaging features.
AB  - This article describes the features on sonography, computed tomography (CT) and
      magnetic resonance imaging (MRI) of mucinous tubular and spindle cell carcinoma
      of the kidney. Six pathologically proven cases of mucinous tubular and spindle
      cell carcinoma of the kidney were identified (5 females, 1 male); all patients
      underwent preoperative imaging. The mean age of the patients was 58.5 years.
      Thirteen imaging studies were available for review: 2 sonograms, 1 unenhanced CT
      scan, 5 contrast-enhanced CT scans, 1 unenhanced magnetic resonance imaging (MRI)
      examination, and 4 contrast-enhanced MRI examinations. Two abdominal radiologists
      evaluated all images retrospectively on a PACS workstation using a standardized
      data collection sheet until consensus was reached. All mucinous tubular and
      spindle cell carcinomas presented as well-marginated, small (mean 2.6 cm, range
      1.9-3.2 cm) predominantly solid masses. No intratumoral fat or calcification was
      identified. Unenhanced CT and MRI appearances were variable as was the degree of
      enhancement following intravenous contrast material administration. There was no
      evidence of perinephric extension, renal vein involvement or metastatic disease
      in any of the cases. The radiological appearance of mucinous tubular and spindle
      cell carcinoma is diverse and therefore indistinguishable from the more common
      subtypes of renal cell carcinoma.

PMID- 22391479
TI  - Si nanowires organic semiconductor hybrid heterojunction solar cells toward 10%
      efficiency.
AB  - High-efficiency hybrid solar cells are fabricated using a simple approach of spin
      coating a transparent hole transporting organic small molecule, 2,2',7,7'
      Tetrakis-(N,N-di-4-methoxyphenylamino)-9,9'-spirobifluorene (Spiro-OMeTAD) on
      silicon nanowires (SiNWs) arrays prepared by electroless chemical etching. The
      characteristics of the hybrid cells are investigated as a function of SiNWs
      length from 0.15 to 5 MUm. A maximum average power conversion efficiency of 9.92%
      has been achieved from 0.35 MUm length SiNWs cells, despite a 12% shadowing loss
      and the absence of antireflective coating and back surface field enhancement. It
      is found that enhanced aggregations in longer SiNWs limit the cell performance
      due to increased series resistance and higher carrier recombination in the
      shorter wavelength region. The effects of the Si substrate doping concentrations
      on the performance of the cells are also investigated. Cells with higher
      substrate doping concentration exhibit a significant drop in the incident photons
      to-current conversion efficiency (IPCE) in the near infrared region.
      Nevertheless, a promising short circuit current density of 19 mA/cm(2) and IPCE
      peak of 57% have been achieved for a 0.9 MUm length SiNWs cell fabricated on a
      highly doped substrate with a minority-carrier diffusion length of only 15 MUm.
      The results suggest that such hybrid cells can potentially be realized using Si
      thin films instead of bulk substrates. This is promising towards realizing low
      cost and high-efficiency SiNWs/organic hybrid solar cells.

PMID- 22391480
TI  - Stroke: TOAST to CASCADE--a childhood stroke classification system.

PMID- 22391481
TI  - Alzheimer disease: DNA damage provides novel and powerful biomarkers of Alzheimer
      disease.

PMID- 22391482
TI  - Micro-coulometric study of bioelectrochemical reaction coupled with TCA cycle.
AB  - The mediated electro-enzymatic electrolysis systems based on the tricarboxylic
      acid (TCA) cycle reaction were examined on a micro-bulk electrolytic system. A
      series of the enzyme-catalyzed reactions in the TCA cycle was coupled with
      electrode reaction. Electrochemical oxidation of NADH was catalyzed by diaphorase
      with an aid of a redox mediator with a formal potential of -0.15 V vs. Ag|AgCl.
      The mediator was also able to shuttle electrons between succinate dehydrogenase
      and electrode. The charge during the electrolysis increased on each addition of
      dehydrogenase reaction in a cascade of the TCA cycle. However, the electrolysis
      efficiencies were close to or less than 90% because of the product inhibition.
      Lactate oxidation to acetyl-CoA catalyzed by two NAD-dependent dehydrogenases was
      coupled with the bioelectrochemical TCA cycle reaction to achieve the 12-electron
      oxidation of lactate to CO(2). The charge passed in the bioelectrocatalytic
      oxidation of 5 nmol of lactate was 4 mC, which corresponds to 70% of the
      electrolysis efficiency.

PMID- 22391483
TI  - Perioperative outcomes of total laparoendoscopic single-site hysterectomy versus
      total robotic hysterectomy in endometrial cancer patients: a multicentre study.
AB  - OBJECTIVE: To compare the peri-operative outcomes between total laparo-endoscopic
      single-site (LESS) and robotic approaches for the staging and treatment of early
      stage endometrial cancer patients. METHODS: A multicentre retrospective study
      involving three Italian gynaecological groups and one American centre. The peri
      operative outcomes of LESS and robotic approach were compared in similar groups
      of patients, with regard to surgical outcomes and intra- and post-operative
      parameters and complications. RESULTS: During the study period, 75 patients
      submitted to a total LESS hysterectomy and 75 patients received a total robotic
      hysterectomy. The median operative time - 122 versus 175 min (p=0.0001) - and the
      estimated blood loss - 50 versus 80 mL (p=0.03) - were slightly more favourable
      in the LESS group. The intra-operative complications were equally distributed
      (p=0.99); in the robotic group there were 4 (5.3%) post-operative grade IIIb
      complications versus 1 (1.3%) in the LESS group (p=0.172). CONCLUSIONS: The LESS
      and robotic approaches both appear reasonable and each may have benefits and
      limitations depending upon the patient population. Further studies are needed to
      validate these preliminary conclusions.

PMID- 22391485
TI  - In silico screening of quadruplex-binding ligands.
AB  - Recent advances in computational processing power and molecular docking
      algorithms have facilitated the development of computer-aided methods for the
      rapid and efficient discovery of G-quadruplex-interacting molecules. In this
      article, we provide an introductory framework for the methodology of in silico
      screening for the identification of novel DNA G-quadruplex ligands from chemical
      libraries. We discuss aspects of model construction, database selection and
      molecular docking techniques, and highlight representative examples from this
      field. Finally, we offer a perspective on the potential application of in silico
      techniques for the discovery of RNA G-quadruplex-binding ligands in the future.

PMID- 22391484
TI  - Novel regulators of planar cell polarity: a genetic analysis in Drosophila.
AB  - Planar cell polarity (PCP) is a common feature of many epithelia and epithelial
      organs. Although progress has been made in the dissection of molecular mechanisms
      regulating PCP, many questions remain. Here we describe a screen to identify
      novel PCP regulators in Drosophila. We employed mild gain-of-function (GOF)
      phenotypes of two cytoplasmic Frizzled (Fz)/PCP core components, Diego (Dgo) and
      Prickle (Pk), and screened these against the DrosDel genome-wide deficiency
      collection for dominant modifiers. Positive genomic regions were rescreened and
      narrowed down with smaller overlapping deficiencies from the Exelixis collection
      and RNAi-mediated knockdown applied to individual genes. This approach isolated
      new regulators of PCP, which were confirmed with loss-of-function analyses
      displaying PCP defects in the eye and/or wing. Furthermore, knockdown of a subset
      was also sensitive to dgo dosage or dominantly modified a dishevelled (dsh) GOF
      phenotype, supporting a role in Fz/PCP-mediated polarity establishment. Among the
      new "PCP" genes we identified several kinases, enzymes required for lipid
      modification, scaffolding proteins, and genes involved in substrate modification
      and/or degradation. Interestingly, one of them is a member of the Meckel-Gruber
      syndrome factors, associated with human ciliopathies, suggesting an important
      role for cell polarity in nonciliated cells.

PMID- 22391486
TI  - Cytometry: today's technology and tomorrow's horizons.
AB  - Flow cytometry has been the premier tool for single cell analysis since its
      invention in the 1960s. It has maintained this position through steady advances
      in technology and applications, becoming the main force behind interrogating the
      complexities of the immune system. Technology development was a three-pronged
      effort, including the hardware, reagents, and analysis algorithms to allow
      measurement of as many as 20 independent parameters on each cell, at tens of
      thousands of cells per second. In the coming years, cytometry technology will
      integrate with other techniques, such as transcriptomics, metabolomics, and so
      forth. Ongoing efforts are aimed at algorithms to analyse these aggregated
      datasaets over large numbers of samples. Here we review the development efforts
      heralding the next stage of flow cytometry.

PMID- 22391487
TI  - Multiplexing and multivariate analysis in neurodegeneration.
AB  - Limited sample volume is often an obstacle in clinical research and one way to
      circumvent this is to use multiplex techniques where several different analytes
      are simultaneously measured. There is a multitude of different platforms that can
      be used for multiplexing and their uniqueness and similarities will be described.
      Multivariate analysis is a powerful tool for extracting information from
      multiplex data. An introduction to one such algorithm is presented followed by
      examples from the literature, in the field of neurodegeneration, where multiplex
      and multivariate methods have been used.

PMID- 22391488
TI  - The design of a double-tuned two-port surface resonator and its application to in
      vivo hydrogen- and sodium-MRI.
AB  - The design and construction of a two-port surface transceiver resonator for both
      (1)H-and (23)Na-MRI in the rodent brain at 7 T is described. Double-tuned
      resonators are required for accurately co-registering multi-nuclei data sets,
      especially when the time courses of (1)H and (23)Na signals are of interest as,
      for instance, when investigating the pathological progression of ischaemic stroke
      tissue in vivo. In the current study, a single-element two-port surface resonator
      was developed wherein both frequency components were measured with the same
      detector element but with each frequency signal routed along different output
      channels. This was achieved by using the null spot technique, allowing for
      optimal variable tuning and matching of each channel in situ within the MRI
      scanner. The (23)Na signal to noise ratio, measured in the ventricles of the rat
      brain, was increased by a factor of four compared to recent state-of-the-art rat
      brain studies reported in the literature. The resonator's performance was
      demonstrated in an in vivo rodent stroke model, where regional variations in (1)H
      apparent diffusion coefficient maps and the (23)Na signal were recorded in an
      interleaved fashion as a function of time in the acute phase of the stroke
      without having to exchange, re-adjust, or re-connect resonators between scans.
      Using the practical construction steps described in this paper, this coil design
      can be easily adapted for MRI of other X-nuclei, such as (17)O, (13)C, (39)K, and
      (43)Ca at various field strengths.

PMID- 22391489
TI  - Inverse field-based approach for simultaneous B1 mapping at high fields - a
      phantom based study.
AB  - Based on computational electromagnetics and multi-level optimization, an inverse
      approach of attaining accurate mapping of both transmit and receive sensitivity
      of radiofrequency coils is presented. This paper extends our previous study of
      inverse methods of receptivity mapping at low fields, to allow accurate mapping
      of RF magnetic fields (B(1)) for high-field applications. Accurate receive
      sensitivity mapping is essential to image domain parallel imaging methods, such
      as sensitivity encoding (SENSE), to reconstruct high quality images. Accurate
      transmit sensitivity mapping will facilitate RF-shimming and parallel
      transmission techniques that directly address the RF inhomogeneity issue,
      arguably the most challenging issue of high-field magnetic resonance imaging
      (MRI). The inverse field-based approach proposed herein is based on computational
      electromagnetics and iterative optimization. It fits an experimental image to the
      numerically calculated signal intensity by iteratively optimizing the coil
      subject geometry to better resemble the experiments. Accurate transmit and
      receive sensitivities are derived as intermediate results of the optimization
      process. The method is validated by imaging studies using homogeneous saline
      phantom at 7T. A simulation study at 300MHz demonstrates that the proposed method
      is able to obtain receptivity mapping with errors an order of magnitude less than
      that of the conventional method. The more accurate receptivity mapping and
      simultaneously obtained transmit sensitivity mapping could enable artefact
      reduced and intensity-corrected image reconstructions. It is hoped that by
      providing an approach to the accurate mapping of both transmit and receive
      sensitivity, the proposed method will facilitate a range of applications in high
      field MRI and parallel imaging.

PMID- 22391490
TI  - The mitral valve...'and miles to go...'.

PMID- 22391491
TI  - Hydrophilic interaction liquid chromatography of anthranilic acid-labelled
      oligosaccharides with a 4-aminobenzoic acid ethyl ester-labelled dextran
      hydrolysate internal standard.
AB  - Hydrophilic interaction liquid chromatography (HILIC) of fluorescently labelled
      oligosaccharides is used in many laboratories to analyse complex oligosaccharide
      mixtures. Separations are routinely performed using a TSK gel-Amide 80 HPLC
      column, and retention times of different oligosaccharide species are converted to
      glucose unit (GU) values that are determined with reference to an external
      standard. However, if retention times were to be compared with an internal
      standard, consistent and more accurate GU values would be obtained. We present a
      method to perform internal standard-calibrated HILIC of fluorescently labelled
      oligosaccharides. The method relies on co-injection of 4-aminobenzoic acid ethyl
      ester (4-ABEE)-labelled internal standard and detection by UV absorption, with 2
      AA (2-aminobenzoic acid)-labelled oligosaccharides. 4-ABEE is a UV chromophore
      and a fluorophore, but there is no overlap of the fluorescent spectrum of 4-ABEE
      with the commonly used fluorescent reagents. The dual nature of 4-ABEE allows for
      accurate calculation of the delay between UV and fluorescent signals when
      determining the GU values of individual oligosaccharides. The GU values obtained
      are inherently more accurate as slight differences in gradients that can
      influence retention are negated by use of an internal standard. Therefore, this
      paper provides the first method for determination of HPLC-derived GU values of
      fluorescently labelled oligosaccharides using an internal calibrant.

PMID- 22391492
TI  - Plasmid DNA partitioning and separation using poly(ethylene
      glycol)/poly(acrylate)/salt aqueous two-phase systems.
AB  - Phase diagrams of poly(ethylene glycol)/polyacrylate/Na(2)SO(4) systems have been
      investigated with respect to polymer size and pH. Plasmid DNA from Escherichia
      coli can depending on pH and polymer molecular weight be directed to a
      poly(ethylene glycol) or to a polyacrylate-rich phase in an aqueous two-phase
      system formed by these polymers. Bovine serum albumin (BSA) and E. coli
      homogenate proteins can be directed opposite to the plasmid partitioning in these
      systems. Two bioseparation processes have been developed where in the final step
      the pDNA is partitioned to a salt-rich phase giving a total process yield of 60
      70%. In one of them the pDNA is partitioned between the polyacrylate and PEG
      phases in order to remove proteins. In a more simplified process the plasmid is
      partitioned to a PEG-phase and back-extracted into a Na(2)SO(4)-rich phase. The
      novel polyacrylate/PEG system allows a strong change of the partitioning between
      the phases with relatively small changes in composition or pH.

PMID- 22391493
TI  - Determination of tropane alkaloids atropine and scopolamine by liquid
      chromatography-mass spectrometry in plant organs of Datura species.
AB  - Hyoscyamine (atropine) and scopolamine are the predominant tropane alkaloids in
      the Datura genus, occurring in all plant organs. The assessment of the alkaloid
      content of various plant parts is essential from the viewpoint of medical use,
      but also as a potential risk of toxicity for humans and animals. Therefore, a
      reliable method for the determination of tropane alkaloid content is of high
      importance. The present work aimed at the elaboration of a rapid method for
      determination of the most abundant Datura alkaloids by LC-MS technique using a
      new generation of core-shell particle packed column. Tropane alkaloid content was
      investigated in various plant organs of four Datura taxa (D. innoxia, D. metel,
      D. stramonium, and D. stramonium var. tatula), grown under the same conditions,
      in two developmental stages. We have developed a rapid LC-MS method for the
      quantitative determination of atropine and scopolamine, which was successfully
      applied to quantify the alkaloids in different plant organs (leaves, flowers,
      stems, seeds) of thorn apples after a simple sample preparation step. Elaboration
      and validation of the method and analysis of plant extracts were done by UFLC-MS
      technique, employing an Ascentis Express C18 column. Detection was done in
      positive ionization mode (ESI+) and the method suitability was evaluated by
      several validation characteristics. Quantitation limits are 333 and 167 pgmL(-1)
      for scopolamine and atropine, respectively, and the method shows very good
      repeatability. The analysis of Datura extracts revealed significant differences
      depending on the species, the organ and the sampling period. Atropine was found
      to be dominant over scopolamine in three out of the four taxa investigated. D.
      innoxia showed the highest concentrations of scopolamine in all organs examined,
      whereas D. metel accumulated the lowest scopolamine levels. Hyoscyamine, measured
      as atropine, was the highest in D. stramonium var. tatula, and the lowest in D.
      innoxia. Samples collected in summer had higher scopolamine levels than autumn
      samples, concerning both stems and leaves.

PMID- 22391494
TI  - Displacement chromatography as first separating step in online two-dimensional
      liquid chromatography coupled to mass spectrometry analysis of a complex protein
      sample--the proteome of neutrophils.
AB  - Displacement chromatography provides some advantages over elution chromatography
      such as the opportunity to enrich trace amounts of molecules and to elute
      molecules in highest concentrations achievable with liquid chromatography. In a
      previous study we demonstrated that displacement chromatography is a well-suited
      alternative to gradient elution in an offline two-dimensional (2D-)LC-MS approach
      for the analysis of proteomes. In this study we present a method for applying
      displacement chromatography in an online 2D-LC-MS system including a cation
      exchange (CEX) column and a reversed phase column. We circumvented the problem of
      determining the sample capacity of the CEX column by repeated injection (pulses)
      of sample aliquots monitored by an LC-MS analysis of each flow-through fraction
      of the CEX column. Elution of tryptic peptides from the CEX column was achieved
      by repeated injection (pulses) of the displacer spermine. Pulsed displacer
      injections offer the advantage through physical separation of preventing post
      column mixing of already separated compounds. As a proof of principle we analyzed
      the cytosolic proteome of human neutrophils.

PMID- 22391495
TI  - Role of fistulography in evaluating pancreatic fistula after
      pancreaticoduodenectomy.
AB  - OBJECTIVE: To evaluate the usefulness of fistulography as a diagnostic and
      management tool for clinically suspected pancreatic fistulas (PF) after
      pancreaticoduodenectomy (PD). METHODS: 84 consecutive fistulographies were
      performed for clinical suspicion of PF and retrospectively analysed. We
      radiologically defined two types of PF by means of fistulography, PF1 in the case
      of primary filling with contrast agent of the jejunal loop or stomach and PF2 in
      the case of secondary filling of the jejunal loop or stomach through a fistulous
      tract or a fluid collection. RESULTS: In 35/84 (41.7%) of the fistulograms, a PF1
      was demonstrated owing to an instantaneous opacification of the intestinal lumen
      or the stomach, without evidence of a fistulous tract or fluid collection. In
      49/84 (58.3%) fistulograms, a PF2 was demonstrated by the depiction of a fluid
      collection and/or a fistulous tract and a communication with the intestinal loop
      or the stomach anastomised with the pancreas. The mean healing time of a PF after
      PD was 2.7 days for PF1, and 9.8 days for PF2. CONCLUSION: Fistulography helps in
      the confirmation of clinically suspect PF, and can distinguish PF1 and PF2, thus
      decreasing post-operative morbidity significantly.

PMID- 22391496
TI  - Effects of employing a 10B-carrier and manipulating intratumour hypoxia on local
      tumour response and lung metastatic potential in boron neutron capture therapy.
AB  - OBJECTIVES: To evaluate the effects of employing a (10)B-carrier and manipulating
      intratumour hypoxia on local tumour response and lung metastatic potential in
      boron neutron capture therapy (BNCT) by measuring the response of intratumour
      quiescent (Q) cells. METHODS: B16-BL6 melanoma tumour-bearing C57BL/6 mice were
      continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P)
      cells. The tumours received reactor thermal neutron beam irradiation following
      the administration of a (10)B-carrier [L-para-boronophenylalanine-(10)B (BPA) or
      sodium mercaptoundecahydrododecaborate-(10)B (BSH)] in combination with an acute
      hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH).
      Immediately after the irradiation, cells from some tumours were isolated and
      incubated with a cytokinesis blocker. The responses of the Q and total (P+Q) cell
      populations were assessed based on the frequency of micronuclei using
      immunofluorescence staining for BrdU. In other tumour-bearing mice, macroscopic
      lung metastases were enumerated 17 days after irradiation. RESULTS: BPA-BNCT
      increased the sensitivity of the total tumour cell population more than BSH-BNCT.
      However, the sensitivity of Q cells treated with BPA was lower than that of BSH
      treated Q cells. With or without a (10)B-carrier, MTH enhanced the sensitivity of
      the Q cell population. Without irradiation, nicotinamide treatment decreased the
      number of lung metastases. With irradiation, BPA-BNCT, especially in combination
      with nicotinamide treatment, showed the potential to reduce the number of
      metastases more than BSH-BNCT. CONCLUSION: BSH-BNCT in combination with MTH
      improves local tumour control, while BPA-BNCT in combination with nicotinamide
      may reduce the number of lung metastases.

PMID- 22391497
TI  - "Black bone" MRI: a partial flip angle technique for radiation reduction in
      craniofacial imaging.
AB  - The potential harmful effects of ionising radiation continue to be highlighted.
      Radiation reduction techniques have largely consisted of low-dose techniques
      rather than a shift to non-ionising methods of imaging. CT scanning is frequently
      employed for imaging the craniofacial skeleton despite being one of the key
      anatomical regions for radiation protection in view of the radiosensitive lens
      and thyroid gland. We describe a low flip angle gradient echo MRI sequence which
      provides high image contrast between bone and other tissues but reduces the
      contrast between individual soft tissues. This permits the "black bone" to be
      easily distinguished from the uniformity of the soft tissues. While maintaining a
      repetition time of 8.6 ms and an echo time of 4.2 ms, the flip angle which
      provided optimised suppression of both fat and water was identified to be 5
      degrees . The biometric accuracy of this sequence was confirmed using a phantom
      to obtain direct anatomical measurements and comparable CT scanning. The average
      discrepancy between black bone MRI measurements and direct anatomical
      measurements was 0.32 mm. Black bone MRI therefore has the potential to reduce
      radiation exposure by replacing CT scanning when imaging the facial skeleton,
      with particular scope for imaging benign conditions in the young.

PMID- 22391498
TI  - Be careful where you inject!

PMID- 22391499
TI  - CT and MRI findings correlate with the time-course of unresectable cavernous
      haemangioma of the liver after fractionated radiotherapy.
AB  - We present the case of a 79-year-old female with symptomatic cavernous
      haemangioma of the liver. The patient had experienced progressive right lateral
      abdominal pain for years despite increased painkiller use. Surgical resection or
      transarterial embolisation was not recommended because of the patient's age,
      cardiovascular comorbidities and large tumour size. Therefore, the patient was
      treated with 3-dimensional conformal radiotherapy (RT) with a total dose of 30 Gy
      in 15 fractions. Following RT, the painkillers were tapered from the third month,
      and complete symptomatic remission was achieved after the ninth month. The
      measured tumour volume from serial images pre-RT and 3, 9 and 15 months post-RT
      was 400 ml, 372 ml, 185 ml and 140 ml, respectively. The most dramatic volumetric
      reduction was found between 3 and 9 months post-RT, whereas the change before or
      after this period was minimal. The time course of the radiological volumetric
      changes correlated with that of the clinical symptoms. In addition, the observed
      vascular changes on serial imaging studies were consistent with the assumed
      radiobiological effects after fractionated RT.

PMID- 22391500
TI  - Retention of iodinated contrast material within renal cysts in a patient with
      autosomal dominant polycystic kidney disease.
AB  - Hyperdense renal cysts, a common condition in autosomal dominant polycystic
      kidney disease, may be induced by haemorrhage into the cysts. However, hyperdense
      renal cysts resulting from retention of contrast material after intravenous
      injection is extremely uncommon because the intravenous administration of
      contrast material does not induce an increase in the attenuation of renal cysts.
      We report a case of retention of iodinated contrast material within renal cysts
      in a patient with autosomal dominant polycystic kidney disease.

PMID- 22391501
TI  - CT appearance of intercostal nerve neurotisation.
AB  - A nerve transfer or neurotisation procedure is performed to repair damaged
      nerves, in particular those of the brachial plexus following an avulsion injury.
      An intercostal to phrenic nerve transfer to re-innervate the diaphragm in
      patients with high cervical spine injury has also been reported in the
      literature. We present the imaging finding in a 65-year-old female who had an
      intercostal nerve transfer for a damaged phrenic nerve following a resection for
      a non-small cell lung carcinoma.

PMID- 22391502
TI  - The MRI findings of a de Garengeot hernia.
AB  - The presence of the appendix within a femoral hernia is rare. It was first
      described by the French surgeon Jacques Croissant de Garengeot in 1731. This
      phenomenon accounts for 0.8-1% of all femoral hernias. Acute appendicitis
      occurring within a femoral hernia is even rarer and is difficult to diagnose pre
      operatively. This type of hernia is termed a de Garengeot hernia. The
      ultrasonographic and CT imaging features of de Garengeot hernias have been
      described previously. We report a case of a 57-year-old female who presented with
      a painful right-sided groin mass. She underwent MRI of the inguinal region, which
      successfully diagnosed this rare hernia pre-operatively. To our knowledge, this
      is the first description of a de Garengeot hernia diagnosed using MRI.

PMID- 22391503
TI  - Erdheim-Chester disease associated with intramedullary spinal cord lesion.
AB  - Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. We
      present a case of a 56-year-old male with ECD. As time progressed, involvement of
      the orbital fossa, cranial convexity, spinal cord, brain stem, thyroid, lung,
      retroperitoneum, lower extremity bones and skin were found. Previously reported
      cases reveal the frequency of ECD with spinal cord involvement is rare. Although
      this was a presumed diagnosis based on other lesions, our case is the first in
      which both intramedullary and epidural masses are present.

PMID- 22391504
TI  - Contrast-enhanced ultrasound in testicular trauma: role in directing exploration,
      debridement and organ salvage.
AB  - We describe the use of contrast-enhanced ultrasound as an additional imaging
      technique during an ultrasound examination of a traumatised testis, allowing for
      confident testicular preserving surgery to be performed.

PMID- 22391505
TI  - MRI and CT findings of metastatic pulmonary calcification.
AB  - Metastatic pulmonary calcification is a consequence of calcium deposition in the
      normal pulmonary parenchyma, secondary to abnormal calcium metabolism. The most
      characteristic radiological manifestation is poorly defined nodular opacities
      that are mainly seen in the upper lung zone. The aim of this report is to
      describe the CT and MRI findings observed in two patients with metastatic
      pulmonary calcification. The disease may present in CT as consolidations with
      calcification, and with a high lesion/muscle signal intensity ratio on T(1)
      weighted imaging without contrast in MRI. The high signal on T(1) weighted
      imaging probably occurs because the low calcium concentration of the lesion
      changes the surface effects of diamagnetic calcium particles, causing T(1)
      shortening of water protons. MRI is a good option for characterising calcium
      accumulation caused by a metabolic disorder.

PMID- 22391506
TI  - The stabilizing role of the rotator cuff at the shoulder--responses to external
      perturbations.
AB  - BACKGROUND: The rotator cuff has been hypothesized as a dynamic stabilizer at the
      shoulder joint yet evidence supporting this role remains inconclusive. We aimed
      to investigate the activity levels and recruitment patterns between the rotator
      cuff and superficial shoulder muscles in response to external perturbations to
      provide insight into the stabilizing role of the rotator cuff. METHODS: Surface
      and intramuscular electromyography (EMG) were used to measure timing of onset and
      level of activation (EMG amplitude as a percentage of maximum voluntary isometric
      contraction, % MVIC) of rotator cuff (supraspinatus, infraspinatus and
      subscapularis) and superficial muscles (anterior and posterior deltoid) on 19
      healthy participants. Participants received expected and unexpected externally
      applied perturbations in directions of internal and external rotation at the
      glenohumeral joint. FINDINGS: All three rotator cuff muscles demonstrated pre
      activation in anticipation of the perturbation prior to their representative
      global synergists, anterior and posterior deltoid (P<0.05). Subscapularis and
      infraspinatus were activated prior to all other muscles during external rotation
      and internal rotation perturbation trials respectively (P<0.01). Direction
      specific activation levels were observed; subscapularis was moderately strongly
      active (37% MVIC) in response to an external rotation perturbation and
      infraspinatus was moderately active (28% MVIC) in response to an internal
      rotation perturbation. No muscle was activated >10% MVIC when not acting as the
      main muscle opposing the movement. INTERPRETATION: The rotator cuff may function
      in part as a dynamic stabilizing unit of the shoulder demonstrating a feedforward
      muscle activation pattern. These results may assist in improving assessment and
      treatment of shoulder dysfunction.

PMID- 22391507
TI  - The relationship between inflammatory activity and brain atrophy in natalizumab
      treated patients.
AB  - OBJECTIVE: To assess the evolution of brain atrophy and its relationship with
      inflammatory activity in RRMS patients treated with natalizumab. METHODS:
      Eighteen RRMS patients were prospectively followed up for 18 months after
      starting natalizumab therapy. Patients were monitored monthly and assessed for
      signs of relapses, adverse events or disability increase. MRI scans were
      performed before starting natalizumab and every six months. Cross-sectional T2
      lesion volume (T2LV) and the normalized brain volume (NBV) at baseline and 18
      months MRI scans were calculated using the Steronauta(r) and SIENAx softwares,
      respectively. Longitudinal Percentage of Brain Volume Change (PBVC) was estimated
      with SIENA. Linkage between inflammatory activity and brain atrophy was studied.
      RESULTS: Natalizumab reduced ARR by 67% and cumulative CEL by 87.5%. T2 lesion
      volume decreased from 1000 mm3, to 960 mm3 (p=0.006) and NBV decreased from
      1.55*10(5) mm3 to 1.42*10(5) mm3 (p=0.025). Global PBVC from baseline to 18
      months was -2.5%, predominantly during the first six months (0-6 months PBVC 
      1.7%; 6-12 months PBVC -0.74%; 12-18 months PBVC -0.50%). The number of relapses
      before treatment was correlated to the PBVC during the first semester (Pearson's
      coefficient -0.520, p=0.003), while the number of basal CEL or baseline T2LV did
      not correlate with brain atrophy rate. During follow-up, nine patients had
      clinical or radiological inflammatory activity. Their PBVC was significantly
      higher in the first semester (-2.3% to -1.1%, p=0.002). CONCLUSIONS: Natalizumab
      reduced relapse rate and CEL in MRI. Brain atrophy predominated in the first
      semester and was related to previous inflammatory activity.

PMID- 22391509
TI  - Recent developments in the study of ionic liquid interfaces using X-ray
      photoelectron spectroscopy and potential future directions.
AB  - A perspective is given on the potential of X-ray photoelectron spectroscopy to
      investigate ionic liquid (IL) interfaces and related bulk properties. To allow
      for cross-correlation of different IL properties, the study is restricted to
      imidazolium-based systems. By systematic variation of alkyl chain lengths, by
      investigation of different anions, and by introduction of functional groups
      detailed information on surface orientation, enrichment effects, cation-anion
      interactions, and the correlation to macroscopic properties such as density and
      surface tension of ILs are derived. Furthermore, the molecular arrangement and
      growth behaviour of ultrathin ionic liquid layers on various substrates, in situ
      monitoring of chemical reactions, and the dissolution of transition metal
      complexes are addressed.

PMID- 22391508
TI  - Single-nucleotide polymorphisms associated with skin naphthyl-keratin adduct
      levels in workers exposed to naphthalene.
AB  - BACKGROUND: Individual genetic variation that results in differences in systemic
      response to xenobiotic exposure is not accounted for as a predictor of outcome in
      current exposure assessment models. OBJECTIVE: We developed a strategy to
      investigate individual differences in single-nucleotide polymorphisms (SNPs) as
      genetic markers associated with naphthyl-keratin adduct (NKA) levels measured in
      the skin of workers exposed to naphthalene. METHODS: The SNP-association analysis
      was conducted in PLINK using candidate-gene analysis and genome-wide analysis. We
      identified significant SNP-NKA associations and investigated the potential impact
      of these SNPs along with personal and workplace factors on NKA levels using a
      multiple linear regression model and the Pratt index. RESULTS: In candidate-gene
      analysis, a SNP (rs4852279) located near the CYP26B1 gene contributed to the 2
      naphthyl-keratin adduct (2NKA) level. In the multiple linear regression model,
      the SNP rs4852279, dermal exposure, exposure time, task replacing foam, age, and
      ethnicity all were significant predictors of 2NKA level. In genome-wide analysis,
      no single SNP reached genome-wide significance for NKA levels (all p >= 1.05 *
      10(-5)). Pathway and network analyses of SNPs associated with NKA levels were
      predicted to be involved in the regulation of cellular processes and homeostasis.
      CONCLUSIONS: These results provide evidence that a quantitative biomarker can be
      used as an intermediate phenotype when investigating the association between
      genetic markers and exposure-dose relationship in a small, well-characterized
      exposed worker population.

PMID- 22391510
TI  - Molecular cloning of chicken interleukin-5 receptor alpha-chain and analysis of
      its binding specificity.
AB  - Interaction between interleukin (IL)-5 and its receptor (IL-5R) is important for
      the regulation of immunity against worm infections, allergic reactions and B cell
      response in mammals. In this study, we identified a full-length cDNA encoding
      chicken IL-5R alpha-chain (chIL-5Ralpha). The deduced amino acid sequence showed
      41-43% identity to mammalian homologues. It has four well-conserved cysteines and
      a WSXWS motif in the extracellular region, and a PPXP motif in the cytoplasmic
      region. Quantitative RT-PCR analysis revealed that chIL-5Ralpha mRNA expression
      was markedly high in bone marrow and relatively high in spleen and lung.
      Recombinant proteins of soluble chIL-5Ralpha and cytokines (artificially produced
      chIL-5 (achIL-5) and another IL-5-like molecule KK34) were expressed by 293F
      cells to examine the cytokine-receptor interactions. Interaction assay using a
      Biacore biosensor showed that chIL-5Ralpha has the capability to bind with
      monomeric achIL-5, but not with KK34. In conclusion, chicken has an IL-5Ralpha
      homologue but KK34 does not complement the IL-5/IL-5R system.

PMID- 22391511
TI  - The effects of age on the spatial and temporal integration of global motion.
AB  - The purpose of this study was to determine the relative contributions of local
      element speed and/or spatial displacement to age-related deficits in global
      motion processing. Motion coherence thresholds (79% correct) were measured for
      discriminating the direction of translational random dot kinematograms (RDKs) as
      a function of dot speed and spatial displacement across the adult lifespan (20-79
      years). Age-related impairments in global motion processing were only apparent in
      observers 70-79 years of age. In agreement with previous studies, we found an age
      related impairment at low (0.625 deg/s) and high speeds (10 deg/s). However,
      these effects were heavily mediated by dot spatial displacement. Motion coherence
      thresholds were also most markedly elevated in women aged over 70 years. These
      findings suggest a prominent role of spatial integration in global motion
      processing. Moreover, global motion perception appears to be relatively well
      preserved until around 70 years of age.

PMID- 22391512
TI  - Motion perception induced by dynamic grouping: a probe for the compositional
      structure of objects.
AB  - A new method is described for determining how the visual system resolves
      ambiguities in the compositional structure of multi-surface objects; i.e., how
      the surfaces of objects are grouped together to form a hierarchical structure.
      The method entails dynamic grouping motion, a high level process in which changes
      in a surface (e.g., increases or decreases in its luminance, hue or texture)
      transiently perturb its affinity with adjacent surfaces. Affinity is determined
      by the combined effects of Gestalt and other grouping variables in indicating
      that a pair of surfaces forms a subunit within an object's compositional
      structure. Such pre-perturbation surface groupings are indicated by the
      perception of characteristic motions across the changing surface. When the
      affinity of adjacent surfaces is increased by a dynamic grouping variable, their
      grouping is transiently strengthened; the perceived motion is away from their
      boundary. When the affinity of adjacent surfaces is decreased, their grouping is
      transiently weakened; the perceived motion is toward the surfaces' boundary. It
      is shown that the affinity of adjacent surfaces depends on the nonlinear, super
      additive combination of affinity values ascribable to individual grouping
      variables, and the effect of dynamic grouping variables on motion perception
      depends on the prior, pre-perturbation affinity state of the surfaces. It is
      proposed that affinity-based grouping of an object's surfaces must be consistent
      with the activation of primitive three-dimensional object components in order for
      the object to be recognized. Also discussed is the potential use of dynamic
      grouping for determining the compositional structure of multi-object scenes.

PMID- 22391513
TI  - HIV neuropathy induced Charcot neuroarthropathy: a case discussion.
AB  - Charcot neuroarthropathy is a devastating joint condition that affects persons
      with neuropathy. With HIV/AIDS treatments prolonging the lives of these persons,
      it is likely that long-term sequelae of the disease will become more evident in
      the near future. Patients with this disease frequently develop peripheral
      neuropathy. A high index of suspicion must be raised in any patient with
      peripheral neuropathy of any cause and a red, hot, swollen, painful foot for
      Charcot neuroarthropathy to give these patients proper treatment to help prevent
      the devastating effects of Charcot neuropathy with its potential consequences
      including foot ulceration and amputation. We present a case of an individual with
      HIV peripheral neuropathy and Charcot neuroarthropathy.

PMID- 22391514
TI  - Differences in psychomotor activity in patients suffering from unipolar and
      bipolar affective disorder in the remitted or mild/moderate depressive state.
AB  - BACKGROUND: Abnormalities in psychomotor activity are a central and essential
      feature of affective disorder. Studies measuring differences in psychomotor
      activity between unipolar and bipolar disorder show divergent results and none
      have used a combined heart rate and movement monitor for measuring activity
      during free-living conditions. OBJECTIVE: To compare objectively measured
      psychomotor activity in patients with unipolar and bipolar disorder in a remitted
      or mild/moderate depressive state. Further, both groups were compared to a
      healthy control group. METHODS: A cross-sectional study of outpatients suffering
      from unipolar (n=20) and bipolar (n=18) disorder and healthy controls (n=31),
      aged 18-60 years. For three consecutive days a combined acceleration (m/s(2)) and
      heart rate (beats per minute) monitoring was used in conjunction with a step test
      to estimate activity energy expenditure (J/min/kg) as measures of psychomotor
      activity and physical fitness. RESULTS: Overall score on Hamilton-17 items ranged
      between 0 and 22. Patients had higher sleeping heart rate (p<0.001), lower
      fitness (p=0.02), lower acceleration (p=0.004), and lower activity energy
      expenditure (p=0.004) compared to controls. Comparing unipolar and bipolar
      patients and adjusting for differences in Hamilton-17 revealed lower acceleration
      (p=0.01) and activity energy expenditure in bipolar patients (p=0.02); the
      difference was most prominent in the morning. CONCLUSIONS: Electronic monitoring
      of psychomotor activity may be a promising additional tool in the distinction
      between unipolar and bipolar affective disorder when patients present in a
      remitted or depressive state.

PMID- 22391515
TI  - Mental disorders and suicide in Japan: a nation-wide psychological autopsy case
      control study.
AB  - BACKGROUND: The purpose of the present nationwide psychological autopsy case
      control study is to identify the association between mental disorders and suicide
      in Japan, adjusting for physical conditions. METHODS: A semi-structured interview
      was conducted of the closest family members of 49 suicide completers and 145
      gender-, age-, and municipality-matched living controls. The interview included
      sections of socio-demographic characteristics, physical conditions, and a
      psychiatric interview producing DSM-IV diagnoses of mental disorders prior to
      suicide (or at survey). We compared prevalences of mental disorders between the
      two groups, using conditional logistic regression. RESULTS: A significantly
      higher proportion with any mental disorder was found in the suicide group (65.3%)
      compared to the control group (4.8%) (p=0.003, odds ratio [OR]=7.5). The
      population attributable risk proportion associated with mental disorder was 0.24.
      Mood disorder, particularly major depressive disorder, was the most strongly
      associated with suicide (p<0.001). Anxiety disorder, alcohol-related disorder,
      and brief psychotic disorder were also significantly associated with suicide
      (p<0.05). These patterns were unchanged after adjusting for serious chronic
      physical conditions. LIMITATIONS: The present study had some limitations, such as
      small sample size, sampling bias and information bias. CONCLUSIONS: Most mental
      disorders, particularly mood disorder, were significantly associated with a
      greater risk of suicide in Japan, independent of physical conditions. Mental
      disorders are a major target of suicide prevention programs in Japan.

PMID- 22391516
TI  - Predictors of change in perceived burden among caregivers of patients with eating
      disorders.
AB  - BACKGROUND: Little is known about whether the perceived burden of caring for
      someone with an eating disorder (ED) changes over time or what may predict such
      change. METHODS: In this prospective study of ED patients and their caregivers,
      caregivers answered the Involvement Evaluation Questionnaire - EU Version (IEQ
      EU), the Hospital Anxiety and Depression Scale (HADS), the SF-12, and the
      Anorectic Behaviour Observation Scale (ABOS) at baseline and after one and two
      years of follow-up. On the same schedule, patients answered the HADS and the SF
      12, as well as the Eating Attitudes Test (EAT-26) and the Health-Related Quality
      of Life in ED - short form (HeRQoLED-s). The psychiatrists assessed ED severity
      using the Clinical Global Impressions (CGI) scale. RESULTS: Perceived caregiver
      burden significantly improved over the first year of follow-up; no further
      improvement was observed with longer follow-up. Reduction in perceived burden was
      associated with lower anxiety in caregivers and patients, and lower caregiver's
      perception of the severity of the patient's ED. With a decrease in patients'
      depressive symptoms, caregivers felt less need to urge them to carry out
      activities of self-care. LIMITATIONS: The IEQ-EU evaluates burden of caring in
      psychosis and mood disorders, but not for EDs. Loss of participants during the
      study could limit the generalization of results for the second year of follow-up.
      CONCLUSIONS: These data corroborate the need to monitor the health of caregivers
      of ED patients and provide them with tools to manage the consequences of these
      disorders, because these consequences can determine the burden perception
      independent of patients' symptoms.

PMID- 22391517
TI  - Depressive episode characteristics and subsequent recurrence risk.
AB  - BACKGROUND: Clinical practice guidelines increasingly recognize the heterogeneity
      associated with major depressive episodes (MDE), e.g. through strategies such as
      watchful waiting. However, the implications of episode heterogeneity for long
      term prognosis have not been adequately explored. METHODS: In this project, we
      used data from a Canadian longitudinal study to evaluate recurrence risks for MDE
      after an initial episode in the mid-1990s. This study collected data from a
      community cohort between 1994/1995 and 2008/2009 using biannual interviews.
      Characteristics of the index episode: syndromal versus sub-syndromal, duration of
      symptoms, and indicators of seriousness (activity restriction, high distress or
      suicidal ideation) were recorded. The ability of these variables to predict MDE
      recurrence was explored using proportional hazards modeling. Additional analyses
      using generalized estimating equations were used to assess robustness. RESULTS:
      Even brief, sub-syndromal episodes not characterized by indicators of seriousness
      were associated with an increased risk of subsequent MDE. However, episodes
      meeting diagnostic criteria for MDE, those lasting longer than four weeks and
      those associated with indicators of seriousness were associated with much higher
      recurrence risk. Sub-syndromal episodes associated with these characteristics
      generally predicted subsequent MDE as strongly as the occurrence of MDE itself.
      LIMITATIONS: The data source did not include assessment of all potentially
      relevant covariates. The assessment of MDE used an abbreviated instrument.
      CONCLUSIONS: Brief sub-syndromal episodes of depression are not usually targets
      of acute treatment, but such episodes have implications for subsequent MDE risk.
      Episode characteristics identify a range of outcomes that have potential
      implications for long-term management.

PMID- 22391518
TI  - Increased inflammation and lower platelet 5-HT in depression with metabolic
      syndrome.
AB  - BACKGROUND: Recent studies suggest comorbidity between major depressive disorder
      (MDD) and metabolic syndrome. For both disorders, impaired serotoninergic
      neurotransmission and inflammatory factors have been suggested. The objective of
      this study was to investigate the concentration of platelet serotonin,
      interleukin-6 (IL-6) and C-reactive protein (CRP) in MDD patients with and
      without metabolic syndrome. The second goal was to investigate the association of
      the concentrations of platelet serotonin, IL-6 and CRP with individual components
      of metabolic syndrome in MDD patients. METHODS: A total of 145 MDD patients were
      included in the study (diagnosed according DSM IV TR criteria). The metabolic
      syndrome was defined according to the criteria of the American National
      Cholesterol Education Program-Treatment Panel III (ATP III). Inflammation factors
      (IL-6 and CRP) and platelet serotonin concentration were assessed by the enzyme
      linked immunosorbent assay (ELISA). RESULTS: MDD patients with metabolic syndrome
      showed lower platelet serotonin and higher IL-6 and CRP concentrations when
      compared to MDD patients without metabolic syndrome. An inverse correlation was
      found between platelet serotonin and waist circumference and serum glucose
      levels. A positive correlation was found between IL-6 and glucose or triglyceride
      concentrations, while the correlation with HDL cholesterol was negative.
      LIMITATIONS: Data on dietary habits or physical activity prior to hospitalisation
      were not collected. Also, the study was a cross-sectional without a prospective
      design. CONCLUSION: Metabolic syndrome in patients with MDD may be associated
      with reduced concentrations of platelet serotonin and increased concentrations of
      IL-6 and CRP.

PMID- 22391519
TI  - Rheumatoid arthritis: Why wait? Explaining delays in seeking therapy for early
      arthritis.

PMID- 22391520
TI  - Repeatability of blood pressure measurements during treadmill exercise.
AB  - OBJECTIVE: Blood pressure measurements during exercise are difficult to obtain
      but are used widely in clinical practice. The objective of this study was to
      investigate the repeatability of blood pressure measurements and gas exchange
      parameters during treadmill exercise. METHODS: Participants were 10 healthy and
      nonsmoking men (age: 26.1 +/- 3.6 years). Each participant performed two
      identical treadmill tests until exhaustion. The blood pressure was measured in
      the right arm before, at 4-min intervals during and just after the exercise test.
      Oxygen consumption, carbon dioxide production and ventilation were measured
      continuously breath-by-breath. Blood lactic acid concentration was measured
      repeatedly. RESULTS: We found that blood pressure measurements during treadmill
      exercise are difficult to obtain. Systolic blood pressure increases with the
      exercise time. Diastolic blood pressure remains constant throughout the
      incrementing exercise test. Systolic blood pressure measurements are more
      repeatable than those of diastolic blood pressure measurements. We found that
      maximal oxygen consumption, obtained by an incrementing treadmill test, is highly
      repeatable and more repeatable than submaximal exercise parameters. CONCLUSION:
      Blood pressure monitoring during exercise testing may provide important clinical
      information that could aid in identifying patients at risk of developing chronic
      hypertension.

PMID- 22391521
TI  - Validation of A&D TM-2430 upper-arm blood pressure monitor for ambulatory blood
      pressure monitoring in children and adolescents, according to the British
      Hypertension Society protocol.
AB  - OBJECTIVE: The A&D TM-2430 ambulatory blood pressure (BP) monitor has been
      validated in adults but not in a young population. We sought to validate the
      device monitoring in children and adolescents, according to the British
      Hypertension Society (BHS) protocol. METHODS: The A&D TM-2430 is an automated
      oscillometric upper-arm device for ambulatory BP monitoring. Nine consecutive
      measurements were taken in 61 children (mean age, 9.8 years; range, 5-15 years)
      according to the BHS criteria. Overseen by an independent supervisor,
      measurements were recorded by two observers blinded from each other's readings
      and from the device readings. RESULTS: The mean difference +/- SD between the
      observers and device measurements was 0.73 +/- 1.64 mmHg for systolic blood
      pressure (SBP) and -1.23 +/- 1.65 mmHg for diastolic blood pressure (DBP),
      respectively, with an interobserver difference of 4 mmHg. The cumulative
      percentages of differences within 5, 10, and 15 mmHg were 89, 95, and 98% for SBP
      and 67, 88, and 98% for DBP. The device achieved a grade A rating for SBP and a B
      grade for DBP. CONCLUSION: The A&D TM-2430 upper-arm BP monitor has fulfilled the
      required BHS standards and can be recommended for measuring ambulatory BP in
      children and adolescent populations.

PMID- 22391522
TI  - Heart rate responses to parental behavior in depressed adolescents.
AB  - In order to more fully understand the abnormalities in emotional responding
      associated with adolescent depression we examined clinically depressed and non
      depressed adolescents' physiological responses to their parents' negative
      emotional behavior, as indexed by their heart rate responses to parental angry
      and dysphoric behavior during laboratory-based interactions. Maternal angry and
      dysphoric behavior predicted heart rate deceleration amongst non-depressed
      adolescents, a response that was not observed in depressed adolescents. Fathers'
      angry behavior predicted significant heart rate acceleration in depressed (but
      not non-depressed) adolescents, whereas fathers' dysphoric behavior predicted
      heart rate deceleration amongst depressed but not amongst non-depressed
      adolescents. These findings are interpreted within the framework of orienting and
      defense cardiac responses, and suggest that reactivity in adolescent depression
      is characterized by the absence of a normative orienting response toward aversive
      maternal behaviors, and a defensive physiological response to aggressive paternal
      behavior.

PMID- 22391523
TI  - From the heart to the mind's eye: cardiac vagal tone is related to visual
      perception of fearful faces at high spatial frequency.
AB  - The neurovisceral integration model (Thayer and Lane, 2000) proposes that vagally
      mediated heart rate variability (HRV)--an index of cardiac vagal tone--is
      associated with autonomic flexibility and emotional self-regulation. Two
      experiments examined the relationship between vagally mediated HRV and visual
      perception of affectively significant stimuli at different spatial frequencies.
      In Experiment 1, HRV was positively correlated with superior performance
      discriminating the emotion of affectively significant (i.e., fearful) faces at
      high spatial frequency (HSF). In Experiment 2, processing goals moderated the
      relationship between HRV and successful discrimination of HSF fearful faces. In
      contrast to Experiment 1, discriminating the expressiveness of HSF fearful faces
      was not correlated with HRV. The current research suggests that HRV is positively
      associated with superior visual discrimination of affectively significant stimuli
      at high spatial frequency, and this relationship may be sensitive to the top-down
      influence of different processing goals.

PMID- 22391524
TI  - Effects of dimerization on the structure and biological activity of antimicrobial
      peptide Ctx-Ha.
AB  - It is well known that cationic antimicrobial peptides (cAMPs) are potential
      microbicidal agents for the increasing problem of antimicrobial resistance.
      However, the physicochemical properties of each peptide need to be optimized for
      clinical use. To evaluate the effects of dimerization on the structure and
      biological activity of the antimicrobial peptide Ctx-Ha, we have synthesized the
      monomeric and three dimeric (Lys-branched) forms of the Ctx-Ha peptide by solid
      phase peptide synthesis using a combination of 9-fluorenylmethyloxycarbonyl
      (Fmoc) and t-butoxycarbonyl (Boc) chemical approaches. The antimicrobial activity
      assay showed that dimerization decreases the ability of the peptide to inhibit
      growth of bacteria or fungi; however, the dimeric analogs displayed a higher
      level of bactericidal activity. In addition, a dramatic increase (50 times) in
      hemolytic activity was achieved with these analogs. Permeabilization studies
      showed that the rate of carboxyfluorescein release was higher for the dimeric
      peptides than for the monomeric peptide, especially in vesicles that contained
      sphingomyelin. Despite different biological activities, the secondary structure
      and pore diameter were not significantly altered by dimerization. In contrast to
      the case for other dimeric cAMPs, we have shown that dimerization selectively
      decreases the antimicrobial activity of this peptide and increases the hemolytic
      activity. The results also show that the interaction between dimeric peptides and
      the cell wall could be responsible for the decrease of the antimicrobial activity
      of these peptides.

PMID- 22391525
TI  - Short-term therapy with luliconazole, a novel topical antifungal imidazole, in
      guinea pig models of tinea corporis and tinea pedis.
AB  - Luliconazole is a novel topical antifungal imidazole with broad-spectrum and
      potent antifungal activity. The drug is under clinical development in the United
      States for management of dermatophytosis with a short-term treatment regimen. The
      present study was undertaken to investigate the clinical benefit of short-term
      therapy with luliconazole cream in guinea pig models of tinea corporis and tinea
      pedis induced with Trichophyton mentagrophytes. The dose-dependent therapeutic
      efficacy of topical luliconazole cream (0.02 to 1%), measured by macroscopic
      improvement of skin lesions and by fungal eradication as determined by a culture
      assay, was demonstrated using a tinea corporis model. The improvement in skin
      lesions seen with luliconazole cream was observed even at a concentration of
      0.02%, and its efficacy at 0.1% was equal to that of 1% bifonazole cream. The
      efficacy of short-term therapy with 1% luliconazole cream, which is used for
      clinical management, was investigated using the tinea corporis model (4- and 8
      day treatment regimens) and the tinea pedis model (7- and 14-day treatment
      regimens). The 1% luliconazole cream completely eradicated the fungus in half or
      less of the treatment time required for 1% terbinafine cream and 1% bifonazole
      cream, as determined by a culture assay for both models. These results clearly
      indicate that 1% luliconazole cream is sufficiently potent for short-term
      treatment for dermatophytosis compared to existing drugs. Luliconazole is
      expected to be useful in the clinical management of dermatophytosis.

PMID- 22391526
TI  - Proveblue (methylene blue) as an antimalarial agent: in vitro synergy with
      dihydroartemisinin and atorvastatin.

PMID- 22391527
TI  - Apicoplast-targeting antibacterials inhibit the growth of Babesia parasites.
AB  - The apicoplast housekeeping machinery, specifically apicoplast DNA replication,
      transcription, and translation, was targeted by ciprofloxacin, thiostrepton, and
      rifampin, respectively, in the in vitro cultures of four Babesia species.
      Furthermore, the in vivo effect of thiostrepton on the growth cycle of Babesia
      microti in BALB/c mice was evaluated. The drugs caused significant inhibition of
      growth from an initial parasitemia of 1% for Babesia bovis, with 50% inhibitory
      concentrations (IC(50)s) of 8.3, 11.5, 12, and 126.6 MUM for ciprofloxacin,
      thiostrepton, rifampin, and clindamycin, respectively. The IC(50)s for the
      inhibition of Babesia bigemina growth were 15.8 MUM for ciprofloxacin, 8.2 MUM
      for thiostrepton, 8.3 MUM for rifampin, and 206 MUM for clindamycin. The IC(50)s
      for Babesia caballi were 2.7 MUM for ciprofloxacin, 2.7 MUM for thiostrepton, 4.7
      MUM for rifampin, and 4.7 MUM for clindamycin. The IC(50)s for the inhibition of
      Babesia equi growth were 2.5 MUM for ciprofloxacin, 6.4 MUM for thiostrepton, 4.1
      MUM for rifampin, and 27.2 MUM for clindamycin. Furthermore, an inhibitory effect
      was revealed for cultures with an initial parasitemia of either 10 or 7% for
      Babesia bovis or Babesia bigemina, respectively. The three inhibitors caused
      immediate death of Babesia bovis and Babesia equi. The inhibitory effects of
      ciprofloxacin, thiostrepton, and rifampin were confirmed by reverse transcription
      PCR. Thiostrepton at a dose of 500 mg/kg of body weight resulted in 77.5%
      inhibition of Babesia microti growth in BALB/c mice. These results implicate the
      apicoplast as a potential chemotherapeutic target for babesiosis.

PMID- 22391528
TI  - In vitro cardiovascular effects of dihydroartemisin-piperaquine combination
      compared with other antimalarials.
AB  - The in vitro cardiac properties of dihydroartemisinin (DHA) plus piperaquine
      phosphate (PQP) were compared with those of other antimalarial compounds. Results
      with antimalarial drugs, chosen on the basis of their free therapeutic maximum
      concentration in plasma (C(max)), were expressed as the fold of that particular
      effect with respect to their C(max). The following tests were used at 37  degrees
      C: hERG (human ether-a-go-go-related gene) blockade and trafficking, rabbit heart
      ventricular preparations, and sodium and slow potassium ion current interference
      (I(Na) and I(Ks), respectively). Chloroquine, halofantrine, mefloquine, and
      lumefantrine were tested in the hERG studies, but only chloroquine, dofetilide,
      lumefantrine, and the combination of artemether-lumefantrine were used in the
      rabbit heart ventricular preparations, hERG trafficking studies, and I(Na) and
      I(Ks) analyses. A proper reference was used in each test. In hERG studies, the
      high 50% inhibitory concentration (IC(50)) of halofantrine, which was lower than
      its C(max), was confirmed. All the other compounds blocked hERG, with IC(50)s
      ranging from 3- to 30-fold their C(max)s. In hERG trafficking studies, the
      facilitative effects of chloroquine at about 30-fold its C(max) were confirmed
      and DHA blocked it at a concentration about 300-fold its C(max). In rabbit heart
      ventricular preparations, dofetilide, used as a positive control, revealed a high
      risk of torsades de pointes, whereas chloroquine showed a medium risk. Neither
      DHA-PQP nor artemether-lumefantrine displayed an in vitro signal for a
      significant proarrhythmic risk. Only chloroquine blocked the I(Na) ion current
      and did so at about 30-fold its C(max). No effect on I(Ks) was detected. In
      conclusion, despite significant hERG blockade, DHA-PQP and artemether
      lumefantrine do not appear to induce potential torsadogenic effects in vitro,
      affect hERG trafficking, or block sodium and slow potassium ion currents.

PMID- 22391530
TI  - Carriage of an ACME II variant may have contributed to methicillin-resistant
      Staphylococcus aureus sequence type 239-like strain replacement in Liverpool
      Hospital, Sydney, Australia.
AB  - Approximately 39% of methicillin-resistant Staphylococcus aureus (MRSA) sequence
      type 239 (ST239)-like bloodstream isolates from Liverpool Hospital (obtained
      between 1997 and 2008) carry an arginine catabolic mobile element (ACME). Whole
      genome sequencing revealed that an ACME II variant is located between orfX and
      SCCmec III, and based on pulsed-field gel electrophoresis patterns and temporal
      relationships of all ST239-like isolates (n = 360), ACME carriage may have
      contributed to subpulsotype strain replacement.

PMID- 22391529
TI  - L-selectin and P-selectin are novel biomarkers of cervicovaginal inflammation for
      preclinical mucosal safety assessment of anti-HIV-1 microbicide.
AB  - A major obstacle thwarting preclinical development of microbicides is the lack of
      a validated biomarker of cervicovaginal inflammation. Therefore, the present
      study aims to identify novel noninvasive soluble markers in a murine model for
      assessment of microbicide mucosal safety. By performing cytokine antibody array
      analysis, we identified two adhesion molecules, L-selectin and P-selectin, which
      significantly increased when mucosal inflammation was triggered by nonoxynol-9
      (N9), an anti-HIV-1 microbicide candidate that failed clinical trials, in a
      refined murine model of agent-induced cervicovaginal inflammation. We found that
      patterns of detection of L-selectin and P-selectin were obviously different from
      those of the two previously defined biomarkers of cervicovaginal inflammation,
      monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6). The levels of
      these two soluble selectins correlated better than those of MCP-1 and IL-6 with
      the duration and severity of mucosal inflammation triggered by N9 and two
      approved proinflammatory compounds, benzalkonium chloride (BZK) and sodium
      dodecyl sulfate (SDS), but not by two nonproinflammatory compounds, carboxymethyl
      celluose (CMC; microbicide excipients) and tenofovir (TFV; microbicide
      candidate). These data indicated that L-selectin and P-selectin can serve as
      additional novel cervicovaginal inflammation biomarkers for preclinical mucosal
      safety evaluation of candidate microbicides for the prevention of infection with
      HIV and other sexually transmitted pathogens.

PMID- 22391531
TI  - Antiviral activity and in vitro mutation development pathways of MK-6186, a novel
      nonnucleoside reverse transcriptase inhibitor.
AB  - MK-6186 is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) which
      displays subnanomolar potency against wild-type (WT) virus and the two most
      prevalent NNRTI-resistant RT mutants (K103N and Y181C) in biochemical assays. In
      addition, it showed excellent antiviral potency against K103N and Y181C mutant
      viruses, with fold changes (FCs) of less than 2 and 5, respectively. When a panel
      of 12 common NNRTI-associated mutant viruses was tested with MK-6186, only 2
      relatively rare mutants (Y188L and V106I/Y188L) were highly resistant, with FCs
      of >100, and the remaining viruses showed FCs of <10. Furthermore, a panel of 96
      clinical virus isolates with NNRTI resistance mutations was evaluated for
      susceptibility to NNRTIs. The majority (70%) of viruses tested displayed
      resistance to efavirenz (EFV), with FCs of >10, whereas only 29% of the mutant
      viruses displayed greater than 10-fold resistance to MK-6186. To determine
      whether MK-6186 selects for novel resistance mutations, in vitro resistance
      selections were conducted with one isolate each from subtypes A, B, and C under
      low-multiplicity-of-infection (MOI) conditions. The results showed a unique
      mutation development pattern in which L234I was the first mutation to emerge in
      the majority of the experiments. In resistance selection under high-MOI
      conditions with subtype B virus, V106A was the dominant mutation detected in the
      breakthrough viruses. More importantly, mutant viruses selected by MK-6186 showed
      FCs of <10 against EFV or etravirine (ETR), and the mutant viruses containing
      mutations selected by EFV or ETR were sensitive to MK-6186 (FCs of <10).

PMID- 22391532
TI  - Recurrent episodes of candidemia due to Candida glabrata with a mutation in hot
      spot 1 of the FKS2 gene developed after prolonged therapy with caspofungin.
AB  - We report two episodes of recurrent candidemia caused by echinocandin-resistant
      Candida glabrata in a 69-year-old patient who underwent repeated abdominal
      surgery. In the first episode of candidemia, an echinocandin-susceptible Candida
      glabrata strain was isolated, and the patient was treated with caspofungin. The
      isolates from the later episodes showed resistance to echinocandins. Analysis of
      the HS1 region of the FKS2 gene showed the amino acid substitution S663P.
      Microsatellite analysis demonstrated a strong genetic relationship between the
      isolates.

PMID- 22391533
TI  - Strand length-dependent antimicrobial activity and membrane-active mechanism of
      arginine- and valine-rich beta-hairpin-like antimicrobial peptides.
AB  - Antimicrobial peptides with amphipathic beta-hairpin-like structures have potent
      antimicrobial properties and low cytotoxicity. The effect of VR or RV motifs on
      beta-hairpin-like antimicrobial peptides has not been investigated. In this
      study, a series of beta-hairpin-like peptides, Ac-C(VR)(n)(D)PG (RV)(n)C-NH(2) (n
      = 1, 2, 3, 4, or 5), were synthesized, and the effect of chain length on
      antimicrobial activity was evaluated. The antimicrobial activity of the peptides
      initially increased and then decreased with chain length. Longer peptides
      stimulated the toxicity to mammalian cells. VR3, a 16-mer peptide with seven
      amino acids in the strand, displayed the highest therapeutic index and represents
      the optimal chain length. VR3 reduced bacterial counts in the mouse peritoneum
      and increased the survival rate of mice at 7 days after Salmonella enterica
      serovar Typhimurium infection in vivo. The circular dichroism (CD) spectra
      demonstrated that the secondary structure of the peptides was a beta-hairpin or
      beta-sheet in the presence of an aqueous and membrane-mimicking environment. VR3
      had the same degree of penetration into the outer and inner membranes as
      melittin. Experiments simulating the membrane environment showed that Trp
      containing VRW3 (a VR3 analog) tends to interact preferentially with negatively
      charged vesicles in comparison to zwitterionic vesicles, which supports the
      biological activity data. Additionally, VR3 resulted in greater membrane damage
      than melittin as determined using a flow cytometry-based membrane integrity
      assay. Collectively, the data for synthetic lipid vesicles and whole bacteria
      demonstrated that the VR3 peptide killed bacteria via targeting the cell
      membrane. This assay could be an effective pathway to screen novel candidates for
      antibiotic development.

PMID- 22391535
TI  - Functional characterization of a Cassette-specific promoter in the class 1
      integron-associated qnrVC1 gene.
AB  - Integrons are natural expression vectors due to the presence of an intrinsic
      promoter (P(c)). Although rare, gene cassettes can harbor their own promoter.
      This study determined the functionality of an internal promoter in the qnrVC1
      cassette whose presence was suggested by a level of transcription similar to that
      of the preceding cassette (aadA2) and confirmed by in silico analysis. Its
      functionality was determined by 5' rapid amplification of cDNA ends (RACE) and
      cloning into promoter-probe vectors. P(qnrVC) was found in the qnrVC cassette
      family, stressing its role in contributing to resistance manifestation.

PMID- 22391534
TI  - Posaconazole exposure-response relationship: evaluating the utility of
      therapeutic drug monitoring.
AB  - Posaconazole has become an important part of the antifungal armamentarium in the
      prophylaxis and salvage treatment of invasive fungal infections (IFIs).
      Structurally related to itraconazole, posaconazole displays low oral
      bioavailability due to poor solubility, with significant drug interactions and
      gastrointestinal disease also contributing to the generally low posaconazole
      plasma concentrations observed in patients. While therapeutic drug monitoring
      (TDM) of plasma concentrations is widely accepted for other triazole antifungal
      agents such as voriconazole, the utility of TDM for posaconazole is controversial
      due to debate over the relationship between posaconazole exposure in plasma and
      clinical response to therapy. This review examines the available evidence for a
      relationship between plasma concentration and clinical efficacy for posaconazole,
      as well as evaluating the utility of TDM and providing provisional target
      concentrations for posaconazole therapy. Increasing evidence supports an exposure
      response relationship for plasma posaconazole concentrations for prophylaxis and
      treatment of IFIs; a clear relationship has not been identified between
      posaconazole concentration and toxicity. Intracellular and intrapulmonary
      concentrations have been studied for posaconazole but have not been correlated to
      clinical outcomes. In view of the high mortality and cost associated with the
      treatment of IFIs, increasing evidence of an exposure-response relationship for
      posaconazole efficacy in the prevention and treatment of IFIs, and the common
      finding of low posaconazole concentrations in patients, TDM for posaconazole is
      likely to be of significant clinical utility. In patients with subtherapeutic
      posaconazole concentrations, increased dose frequency, administration with high
      fat meals, and withdrawal of interacting medications from therapy are useful
      strategies to improve systemic absorption.

PMID- 22391536
TI  - NDM-1-producing Klebsiella pneumoniae now in Turkey.

PMID- 22391537
TI  - First pharmacokinetic and safety study in humans of the novel lipid antiviral
      conjugate CMX001, a broad-spectrum oral drug active against double-stranded DNA
      viruses.
AB  - CMX001 is a novel, broad-spectrum lipid antiviral conjugate (LAC) that produces
      high intracellular levels of the active antiviral agent cidofovir diphosphate
      (CDV-PP). Study CMX001-102 was a randomized, double-blind, placebo-controlled,
      parallel group, dose-escalating study in healthy volunteers. The objectives of
      the study were to evaluate the safety and pharmacokinetic parameters of CMX001
      after single and multiple doses. Single doses ranging from 0.25 to 2.0 mg/kg of
      body weight and multiple doses ranging from 0.1 to 1.0 mg/kg (3 total doses,
      administered every 6 days) were given orally. Safety was assessed using
      comprehensive clinical and laboratory evaluations, including enhanced monitoring
      for potential gastrointestinal (GI) effects using wireless capsule endoscopy
      (WCE). Serial plasma and pooled urine samples were collected to estimate
      pharmacokinetic parameters for both CMX001 and cidofovir (CDV). No adverse events
      occurred that prevented dose escalation. No clinically significant drug-related
      changes in blood chemistry, hematology, renal function, or intraocular pressure
      were observed. No CMX001-related gastrointestinal mucosal changes were observed
      by WCE. CMX001 was absorbed rapidly, with maximum plasma concentrations observed
      2 to 3 h postdose. Maximum plasma drug concentration and systemic exposure of
      CMX001 increased approximately in proportion to dose following single and
      multiple doses; no significant accumulation of CMX001 or CDV was observed
      following multiple doses. We conclude that CMX001 is orally bioavailable and well
      tolerated in healthy volunteers at doses up to 2 mg/kg, approximately 140 mg in a
      typical adult. This is the first demonstration of the use of phospholipid
      conjugation technology to achieve plasma drug exposures that are expected to
      result in activity against multiple double-stranded DNA viruses.

PMID- 22391538
TI  - Targeting persisters for tuberculosis control.
AB  - Mycobacterial persisters, the survivors from antibiotic exposure, necessitate the
      lengthy treatment of tuberculosis (TB) and pose a significant challenge for our
      control of the disease. We suggest that persisters in TB are heterogeneous in
      nature and comprise various proportions of the population depending on the
      circumstances; the mechanisms of their formation are complex and may be related
      to those required for persistence in chronic infection. Results from recent
      studies implicate multiple pathways for persister formation, including energy
      production, the stringent response, global regulators, the trans-translation
      pathway, proteasomal protein degradation, toxin-antitoxin modules, and
      transporter or efflux mechanisms. A combination of specifically persister
      targeted approaches, such as catching them when active and susceptible either by
      stimulating them to "wake up" or by intermittent drug dosing, the development of
      new drugs, the use of appropriate drug combinations, and combined chemotherapy
      and immunotherapy, may be needed for more effective elimination of persisters and
      better treatment of TB. Variations in levels of persister formation and in host
      genetics can play a role in the outcome of clinical treatment, and thus, these
      may entail personalized treatment regimens.

PMID- 22391539
TI  - In vitro interactions between aspirin and amphotericin B against planktonic cells
      and biofilm cells of Candida albicans and C. parapsilosis.
AB  - The increase in drug resistance and invasion caused by biofilm formation brings
      enormous challenges to the management of Candida infection. Aspirin's antibiofilm
      activity in vitro was discovered recently. The spectrophotometric method and the
      XTT {2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H
      tetrazolium hydroxide} reduction assay used for data generation make it possible
      to evaluate fungal biofilm growth accurately. The combined use of the most
      commonly used methods, the fractional inhibitory concentration index (FICI) and a
      newly developed method, the DeltaE model, which uses the concentration-effect
      relationship over the whole concentration range instead of using the MIC index
      alone, makes the interpretation of results more reliable. As an attractive tool
      for studying the pharmacodynamics of antimicrobial agents, time-kill curves can
      provide detailed information about antimicrobial efficacy as a function of both
      time and concentration. In the present study, in vitro interactions between
      aspirin (acetylsalicylic acid [ASA]) and amphotericin B (AMB) against planktonic
      cells and biofilm cells of Candida albicans and C. parapsilosis were evaluated by
      the checkerboard microdilution method and the time-kill test. Synergistic and
      indifferent effects were found for the combination of ASA and AMB against
      planktonic cells, while strong synergy was found against biofilm cells analyzed
      by FICI. The DeltaE model gave more consistent results with FICI. The positive
      interactions in concentration were also confirmed by the time-kill test.
      Moreover, this approach also revealed the pharmacodynamics changes of ASA and
      synergistic action on time. Our findings suggest a potential clinical use for
      combination therapy with ASA and AMB to augment activity against biofilm
      associated infections.

PMID- 22391540
TI  - Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for
      multidrug-resistant tuberculosis: long-term outcome, tolerability, and effect on
      emergence of drug resistance.
AB  - The 2-year follow-up results for a randomized placebo-controlled study of 47
      patients with multidrug-resistant pulmonary tuberculosis treated with either the
      new diarylquinoline TMC207, recently renamed bedaquiline, or placebo, added to
      the first 8 weeks of a background regimen, are presented. Bedaquiline
      significantly reduced the time to culture conversion over 24 weeks (hazard ratio,
      2.253; 95% confidence interval, 1.08 to 4.71; P = 0.031). With the exception of
      nausea reported in 26% of patients receiving bedaquiline and none receiving
      placebo, adverse events occurred at similar frequencies in both groups of
      patients: bilateral hearing impairment, extremity pain, acne, and noncardiac
      chest pain occurred in 13 and 21%, 17 and 13%, 9 and 17%, and 4 and 17% of
      patients, respectively, receiving bedaquiline or placebo. Excluding resistance to
      ethambutol and ethionamide, only one patient receiving bedaquiline acquired
      resistance to companion drugs, but five patients receiving placebo (4.8% versus
      21.7%; P = 0.18) acquired resistance to companion drugs, and resistance to
      ofloxacin was acquired in four patients receiving placebo and none receiving
      bedaquiline (0% versus 22%; 0 = 0.066). In all, 23 patients (49%), including 13
      receiving placebo (54%) and 10 receiving bedaquiline (44%), discontinued the
      study prior to its completion, 12 during the first 24 weeks of treatment. Eight
      subjects were withdrawn for noncompliance or default, and seven withdrew consent,
      citing the rigorous program of investigations for safety and pharmacokinetic
      monitoring. Bedaquiline may contribute to the management of multidrug-resistant
      tuberculosis by effecting more rapid sputum culture negativity and by preventing
      acquired resistance to companion drugs.

PMID- 22391542
TI  - Activity of a novel cyclic lipopeptide, CB-183,315, against resistant Clostridium
      difficile and other Gram-positive aerobic and anaerobic intestinal pathogens.
AB  - We evaluated the activity of CB-183,315 against Clostridium difficile, including
      strains that are resistant to fluoroquinolones and metronidazole and with
      elevated MICs to vancomycin as well as other Gram-positive intestinal pathogens.
      The MICs of CB-183,315 against all C. difficile isolates were <= 1 MUg/ml. CB
      183,315 had greater activity than vancomycin and metronidazole against C.
      difficile isolates and was more active than the comparators against vancomycin
      resistant enterococcus (VRE). CB-183,315 also had excellent activity against
      methicillin-resistant Staphylococcus aureus (MRSA), other Clostridium spp., and
      Peptostreptococcus spp.

PMID- 22391541
TI  - Effect of HIV-1 infection and sex on the cellular pharmacology of the
      antiretroviral drugs zidovudine and lamivudine.
AB  - The cellular pharmacology of zidovudine (ZDV) and lamivudine (3TC) in vivo is not
      completely understood. This prospective longitudinal study investigated the
      relationship between HIV-1 serostatus, sex, race, and time on therapy with
      intracellular and plasma ZDV and 3TC concentrations. Of 20 HIV-seronegative and
      23 HIV-seropositive volunteers enrolled, 16 (8 women) and 21 (5 women) completed
      all 12 study days, respectively. Volunteers began ZDV-3TC therapy (plus a third
      active drug in HIV-seropositive volunteers), and steady-state concentrations
      (C(ss)) were determined after days 1, 3, 7, and 12. A repeated-measures mixed
      model was utilized. HIV-seronegative status was associated with 22% (95%
      confidence interval [CI], 0%, 50%) and 37% (15%, 67%) higher C(ss) estimates
      compared to those of HIV-seropositive individuals for intracellular ZDV-TP and
      3TC-TP levels, respectively. African-Americans had 36% (8%, 72%) higher ZDV-TP
      estimates than non-African-Americans. Sex was not associated with ZDV-TP or 3TC
      TP (P > 0.19). Women had 36% (4%, 78%) higher plasma ZDV, but the effect was
      lessened when normalized by lean body weight (5% [-19%, 38%]; P = 0.68). Plasma
      3TC was 19% (0%, 41%) higher in HIV-seropositive volunteers and 22% (0%, 48%)
      higher in African American volunteers, but these effects were not significant
      when corrected for creatinine clearance (7% [-9%, 20%] and -5% [-26%, 12%] for
      HIV serostatus and race, respectively; P > 0.35). These results suggest that HIV
      seropositive status decreases and African American race elevates the cellular
      triphosphates of ZDV and 3TC. This information extends knowledge of ZDV and 3TC
      cellular pharmacology in vivo and provides new leads for future cellular
      pharmacology studies aimed at optimizing HIV prevention/treatment with these
      agents.

PMID- 22391543
TI  - Bactericidal activity of multiple combinations of tigecycline and colistin
      against NDM-1-producing Enterobacteriaceae.
AB  - The interaction between colistin and tigecycline against eight well-characterized
      NDM-1-producing Enterobacteriaceae strains was studied. Time-kill methodology was
      employed using a 4-by-4 exposure matrix with pharmacokinetically achievable free
      drug peak, trough, and average 24-h serum concentrations. Colistin sulfate and
      methanesulfonate alone showed good early bactericidal activity, often with
      subsequent regrowth. Tigecycline alone had poor activity. Addition of tigecycline
      to colistin does not produce increased bacterial killing; instead, it may cause
      antagonism at lower concentrations.

PMID- 22391544
TI  - Empirical use of ciprofloxacin for acute uncomplicated pyelonephritis caused by
      Escherichia coli in communities where the prevalence of fluoroquinolone
      resistance is high.
AB  - There is little information about the effectiveness of ciprofloxacin in regions
      where ciprofloxacin-resistant Escherichia coli is prevalent. This study was
      conducted to evaluate whether ciprofloxacin is effective as the initial empirical
      antibiotic for treatment of uncomplicated acute pyelonephritis (APN) due to
      ciprofloxacin-resistant E. coli. A total of 255 women with clinical diagnoses of
      uncomplicated APN due to E. coli were enrolled in the emergency department
      between March 2005 and December 2008. All enrolled patients were initially
      treated with ciprofloxacin. Patients were followed up 4 to 7 days after the start
      of therapy and 14 to 21 days after its completion. At the first follow-up visit,
      ciprofloxacin was changed to the appropriate antibiotic when necessary, depending
      on the antibiotic susceptibility results. Not only improvement of symptoms and
      signs but also microbiologic eradication was assessed at each visit. Fifteen
      percent (39/255) of the E. coli isolates were resistant to ciprofloxacin. There
      was no statistically significant difference between the clinical cure rates of
      the ciprofloxacin-susceptible group and the ciprofloxacin-resistant group at the
      first follow-up (87.0% versus 76.9%, P = 0.135) or the second follow-up (98.6%
      versus 94.9%, P = 0.177). However, there was a lower microbiologic cure rate in
      the ciprofloxacin-resistant group than in the ciprofloxacin-susceptible group
      (92.4% versus 41.7%, P = 0.000) at the first follow-up visit. No complications
      occurred in the ciprofloxacin-resistant group during the follow-up period. Our
      findings indicate that ciprofloxacin is an appropriate choice for empirical
      therapy of uncomplicated APN and has no serious adverse outcomes, if it is
      tailored appropriately, even for women infected with ciprofloxacin-resistant E.
      coli.

PMID- 22391545
TI  - Prevalence of qnr, aac(6')-Ib-cr, qepA, and oqxAB in Escherichia coli isolates
      from humans, animals, and the environment.
AB  - qnr, aac(6')-Ib-cr, qepA, and oqxAB genes were detected in 5.7%, 4.9%, 2.6%, and
      20.2% of 1,022 Escherichia coli isolates from humans, animals, and the
      environment, respectively, collected between 1993 and 2010 in China. The
      prevalence of oqxAB in porcine isolates (51.0%) was significantly higher than
      that in other isolates. This is the first report of oqxAB-positive isolates from
      ducks and geese and as early as 1994 from chickens.

PMID- 22391546
TI  - Cryptococcus neoformans-Cryptococcus gattii species complex: an international
      study of wild-type susceptibility endpoint distributions and epidemiological
      cutoff values for amphotericin B and flucytosine.
AB  - Clinical breakpoints (CBPs) are not available for the Cryptococcus neoformans
      Cryptococcus gattii species complex. MIC distributions were constructed for the
      wild type (WT) to establish epidemiologic cutoff values (ECVs) for C. neoformans
      and C. gattii versus amphotericin B and flucytosine. A total of 3,590
      amphotericin B and 3,045 flucytosine CLSI MICs for C. neoformans (including 1,002
      VNI isolates and 8 to 39 VNII, VNIII, and VNIV isolates) and 985 and 853 MICs for
      C. gattii, respectively (including 42 to 259 VGI, VGII, VGIII, and VGIV
      isolates), were gathered in 9 to 16 (amphotericin B) and 8 to 13 (flucytosine)
      laboratories (Europe, United States, Australia, Brazil, Canada, India, and South
      Africa) and aggregated for the analyses. Additionally, 442 amphotericin B and 313
      flucytosine MICs measured by using CLSI-YNB medium instead of CLSI-RPMI medium
      and 237 Etest amphotericin B MICs for C. neoformans were evaluated. CLSI-RPMI
      ECVs for distributions originating in >=3 laboratories (with the percentages of
      isolates for which MICs were less than or equal to ECVs given in parentheses)
      were as follows: for amphotericin B, 0.5 MUg/ml for C. neoformans VNI (97.2%) and
      C. gattii VGI and VGIIa (99.2 and 97.5%, respectively) and 1 MUg/ml for C.
      neoformans (98.5%) and C. gattii nontyped (100%) and VGII (99.2%) isolates; for
      flucytosine, 4 MUg/ml for C. gattii nontyped (96.4%) and VGI (95.7%) isolates, 8
      MUg/ml for VNI (96.6%) isolates, and 16 MUg/ml for C. neoformans nontyped (98.6%)
      and C. gattii VGII (97.1%) isolates. Other molecular types had apparent
      variations in MIC distributions, but the number of laboratories contributing data
      was too low to allow us to ascertain that the differences were due to factors
      other than assay variation. ECVs may aid in the detection of isolates with
      acquired resistance mechanisms.

PMID- 22391547
TI  - Development of a robust cytopathic effect-based high-throughput screening assay
      to identify novel inhibitors of dengue virus.
AB  - We have developed a robust cytopathic effect-based high-throughput screening
      assay to identify inhibitors of dengue virus (DENV) infection. Screening of a
      small natural product library yielded 11 hits. Four of these were found to be
      potent inhibitors of DENV, although serotype differences were noted. Taken
      together, these data suggest that screening of larger and more complex molecule
      libraries may result in the identification of more potent and specific DENV
      inhibitors.

PMID- 22391548
TI  - In vitro antimicrobial susceptibility to isepamicin of 6,296 Enterobacteriaceae
      clinical isolates collected at a tertiary care university hospital in Greece.
AB  - The reevaluation of "forgotten" antibiotics can identify new therapeutic options
      against extensively drug-resistant Gram-negative pathogens. We sought to
      investigate isepamicin in this regard. We retrospectively evaluated the
      antimicrobial susceptibility to isepamicin of Enterobacteriaceae sp. isolates
      from unique patients, collected at the microbiological laboratory of the
      University Hospital of Heraklion, Crete, Greece, from 2004 to 2009.
      Susceptibility testing was done with the automated Vitek 2 system. The
      breakpoints for susceptibility to isepamicin, tigecycline, and other antibiotics
      were those proposed by the Comite de l'Antibiogramme de la Societe Francaise de
      Microbiologie (CA-SFM), the FDA, and the CLSI, respectively. A total of 6,296
      isolates were studied, including primarily 3,401 (54.0%) Escherichia coli, 1,040
      (16.5%) Klebsiella pneumoniae, 590 (9.4%) Proteus mirabilis, and 460 (7.3%)
      Enterobacter sp. isolates. Excluding the species with intrinsic resistance to
      each antibiotic, antimicrobial susceptibility was highest for colistin
      (5,275/5,441 isolates [96.9%]) and isepamicin (6,103/6,296 [96.9%]), followed by
      meropenem (5,890/6,296 [93.6%]), imipenem (5,874/6,296 [93.3%]), and amikacin
      (5,492/6,296 [87.2%]). The antimicrobial susceptibility of the 1,040 K.
      pneumoniae isolates was highest for isepamicin (95.3%), followed by colistin
      (89.3%) and meropenem (63.0%). Regarding resistant K. pneumoniae isolates,
      susceptibility to isepamicin was observed for 91.1% of the 392, 87.7% of the 375,
      and 85.6% of the 111 isolates that were nonsusceptible to the carbapenems, all
      other aminoglycosides, and colistin, respectively. Isepamicin exhibited high in
      vitro activity against almost all of the Enterobacteriaceae species. It could
      particularly serve as a last-resort therapeutic option for carbapenem-resistant
      K. pneumoniae in our region, where it is endemic, as it does not show
      considerable cross-resistance with other aminoglycosides.

PMID- 22391549
TI  - Effects of antibiotics on Shiga toxin 2 production and bacteriophage induction by
      epidemic Escherichia coli O104:H4 strain.
AB  - The role of antibiotics in treatment of enterohemorrhagic Escherichia coli (EHEC)
      infections is controversial because of concerns about triggering hemolytic-uremic
      syndrome (HUS) by increasing Shiga toxin (Stx) production. During the recent
      large EHEC O104:H4 outbreak, antibiotic therapy was indicated for some patients.
      We tested a diverse panel of antibiotics to which the outbreak strain is
      susceptible to interrogate the effects of subinhibitory antibiotic concentrations
      on induction of stx(2)-harboring bacteriophages, stx(2) transcription, and Stx2
      production in this emerging pathogen. Ciprofloxacin significantly increased
      stx(2)-harboring phage induction and Stx2 production in outbreak isolates (P
      values of <0.001 to <0.05), while fosfomycin, gentamicin, and kanamycin
      insignificantly influenced them (P > 0.1) and chloramphenicol, meropenem,
      azithromycin, rifaximin, and tigecycline significantly decreased them (P <=
      0.05). Ciprofloxacin and chloramphenicol significantly upregulated and
      downregulated stx(2) transcription, respectively (P < 0.01); the other
      antibiotics had insignificant effects (P > 0.1). Meropenem, azithromycin, and
      rifaximin, which were used for necessary therapeutic or prophylactic
      interventions during the EHEC O104:H4 outbreak, as well as tigecycline, neither
      induced stx(2)-harboring phages nor increased stx(2) transcription or Stx2
      production in the outbreak strain. These antibiotics might represent therapeutic
      options for patients with EHEC O104:H4 infection if antibiotic treatment is
      inevitable. We await further analysis of the epidemic to determine if usage of
      these agents was associated with an altered risk of developing HUS.

PMID- 22391550
TI  - Detection and characterization of VIM-31, a new variant of VIM-2 with Tyr224His
      and His252Arg mutations, in a clinical isolate of Enterobacter cloacae.
AB  - We report the first description of the metallo-beta-lactamase VIM-31, a new
      variant of VIM-2 with Tyr224His and His252Arg mutations, in Enterobacter cloacae
      11236, which was isolated from blood specimens of a patient with colonic
      adenocarcinoma in Belgium. bla(VIM-31) was found on a class 1 integron located on
      a self-transferable but not typeable 42-kb plasmid. Compared to values published
      elsewhere for VIM-2, the purified VIM-31 enzyme showed weaker catalytic
      efficiency against all the tested beta-lactam agents (except for ertapenem),
      resulting from lower k(cat) (except for ertapenem) and higher K(m) values for VIM
      31.

PMID- 22391551
TI  - The aminoglycoside antibiotic kanamycin damages DNA bases in Escherichia coli:
      caffeine potentiates the DNA-damaging effects of kanamycin while suppressing cell
      killing by ciprofloxacin in Escherichia coli and Bacillus anthracis.
AB  - The distribution of mutants in the Keio collection of Escherichia coli gene
      knockout mutants that display increased sensitivity to the aminoglycosides
      kanamycin and neomycin indicates that damaged bases resulting from antibiotic
      action can lead to cell death. Strains lacking one of a number of glycosylases
      (e.g., AlkA, YzaB, Ogt, KsgA) or other specific repair proteins (AlkB, PhrB,
      SmbC) are more sensitive to these antibiotics. Mutants lacking AlkB display the
      strongest sensitivity among the glycosylase- or direct lesion removal-deficient
      strains. This perhaps suggests the involvement of ethenoadenine adducts,
      resulting from reactive oxygen species and lipid peroxidation, since AlkB removes
      this lesion. Other sensitivities displayed by mutants lacking UvrA, polymerase V
      (Pol V), or components of double-strand break repair indicate that kanamycin
      results in damaged base pairs that need to be removed or replicated past in order
      to avoid double-strand breaks that saturate the cellular repair capacity.
      Caffeine enhances the sensitivities of these repair-deficient strains to
      kanamycin and neomycin. The gene knockout mutants that display increased
      sensitivity to caffeine (dnaQ, holC, holD, and priA knockout mutants) indicate
      that caffeine blocks DNA replication, ultimately leading to double-strand breaks
      that require recombinational repair by functions encoded by recA, recB, and recC,
      among others. Additionally, caffeine partially protects cells of both Escherichia
      coli and Bacillus anthracis from killing by the widely used fluoroquinolone
      antibiotic ciprofloxacin.

PMID- 22391552
TI  - The composition of the culture medium influences the beta-1,3-glucan metabolism
      of Aspergillus fumigatus and the antifungal activity of inhibitors of beta-1,3
      glucan synthesis.
AB  - In vitro testing of Aspergillus fumigatus susceptibility to echinocandins has
      always been a challenge. Using a simple and quick colorimetric method to analyze
      the activity of inhibitors of beta-1,3-glucan synthesis, we found that the
      composition of the culture medium significantly influences glucan synthesis and
      consequently the antifungal properties of inhibitors of beta-1,3-glucan synthesis
      when they are tested alone or in combination with chitin synthase inhibitors.

PMID- 22391553
TI  - Assessment of the pharmacokinetic interaction between eltrombopag and lopinavir
      ritonavir in healthy adult subjects.
AB  - Eltrombopag is an orally bioavailable thrombopoietin receptor agonist that is
      approved for the treatment of chronic idiopathic thrombocytopenic purpura. It is
      being developed for other medical disorders that are associated with
      thrombocytopenia. Patients with human immunodeficiency virus (HIV) may suffer
      from thrombocytopenia as a result of their HIV disease or coinfection with
      hepatitis C virus (HCV). HIV medications, particularly ritonavir (RTV)-boosted
      HIV protease inhibitors, are involved in many drug interactions. This study
      evaluated the potential drug-drug interaction between eltrombopag and lopinavir
      (LPV)/RTV. Forty healthy adult subjects enrolled in this open-label, three
      period, single-sequence crossover study received a single 100-mg dose of
      eltrombopag (period 1), LPV/RTV at 400/100 mg twice daily (BID) for 14 days
      (period 2), and LPV/RTV at 400/100 mg BID (2 doses) with a single 100-mg dose of
      eltrombopag administered with the morning LPV/RTV dose (period 3). There was a 3
      day washout between periods 1 and 2 and no washout between periods 2 and 3.
      Serial pharmacokinetic samples were collected during 72 h in periods 1 and 3 and
      during 12 h in period 2. The coadministration of 400/100 mg LPV/RTV BID with a
      single dose of 100 mg eltrombopag decreased the plasma eltrombopag area under the
      plasma concentration-time curve from time zero extrapolated to infinity (AUC(0
      infinity)) by 17%, on average, with no change in plasma LPV/RTV exposure. Adverse
      events (AEs) reported in period 2 were consistent with known LPV/RTV AEs, such as
      diarrhea, abdominal pain, nausea, vomiting, rash, and fatigue. No subjects
      withdrew due to AEs, and no serious AEs were reported. These study results
      suggest that platelet counts should be monitored and the eltrombopag dose
      adjusted accordingly if LPV/RTV therapy is initiated or discontinued.

PMID- 22391554
TI  - Pharmacokinetics and disposition study of calf thymus DNA in rats by applying 3H
      labeling method.
AB  - A tritium((3)H)-labeling method with high specificity was established to
      investigate the pharmacokinetics and disposition of the calf thymus DNA (ctDNA)
      in rats. The plasma pharmacokinetics, tissue distribution, mass balance and
      excretion were characterized in SD rats, respectively. Rats were injected i.v.
      with radiolabeled ctDNA with the dose of 40MUCi/kg in each independent
      experiment. (3)H-labeled ctDNA was eliminated rapidly in plasma, with the half
      life estimated from 9 to 13h and preferentially accumulated in liver and lung,
      its concentration in all the tissues investigated decreased to very low level
      after 24h. ctDNA exhibited 80.8% accumulative recovery, excretion of radiolabel
      in urine and bile was nearly complete by 72h, which shown as the main excretion
      pathways, and the total recovery of excretion reached 77.9% within three days. In
      conclusion, ctDNA was rapidly eliminated in plasma and would not accumulate in
      tissues, parent ctDNA and its radioactive metabolites can be recovered almost
      completely in schedule time. All the results indicated that the in vitro use of
      ctDNA is safe and will not bring out potential risk.

PMID- 22391555
TI  - Acetylcholinesterase capillary enzyme reactor for screening and characterization
      of selective inhibitors.
AB  - The aim of the present work is to report on the optimized preparation of
      capillary enzyme reactors (ICERs) based on acetylcholinesterase (AChE, EC
      3.1.1.7), for the screening of selective inhibitors. The AChE-ICERs were prepared
      by using the homobifunctional linker glutaraldehyde through Schiff base linkage.
      The enzyme was anchored onto a modified fused silica capillary and employed as an
      LC biochromatography column for online studies, with UV-vis detection. Not only
      did the tailored AChE-ICER result in maintenance of the activity of the
      immobilized enzyme, but it also significantly improved the stability of the
      enzyme in the presence of organic solvents. In addition, the kinetic studies
      demonstrated that the enzyme retained its activity with high stability,
      preserving its initial activity over 10months. The absence of non-specific matrix
      interactions, immediate recovery of the enzymatic activity, and short analysis
      time were the main advantages of this AChE-ICER. The use of AChE-ICER in the
      ligands recognition assay was validated by evaluation of four known reversible
      inhibitors (galanthamine, tacrine, propidium, and rivastigmine), and the same
      order of inhibitory potencies described in the literature was found. The
      immobilized enzyme was utilized in the screening of 21 coumarin derivatives. In
      this library, two new potent inhibitors were identified: coumarins 20 (IC(50)
      17.14+/-3.50MUM) and 21 (IC(50) 6.35+/-1.20MUM), which were compared to the
      standard galanthamine (IC(50) 12.68+/-2.40MUM). Considering the high inhibitory
      activities of these compounds, with respect to the AChE-ICER, the mechanism of
      action was investigated. Both coumarins 20 and 21 exhibited a competitive
      mechanism of action, furnishing K(i) values of 8.04+/-0.18 and 2.67+/-0.18MUM,
      respectively. The results revealed that the AChE-ICER developed herein represents
      a useful tool for the biological screening of inhibitor candidates and evaluation
      of action mechanism.

PMID- 22391556
TI  - A DNA hypermethylation module for the stem/progenitor cell signature of cancer.
AB  - Many DNA-hypermethylated cancer genes are occupied by the Polycomb (PcG)
      repressor complex in embryonic stem cells (ESCs). Their prevalence in the full
      spectrum of cancers, the exact context of chromatin involved, and their status in
      adult cell renewal systems are unknown. Using a genome-wide analysis, we
      demonstrate that ~75% of hypermethylated genes are marked by PcG in the context
      of bivalent chromatin in both ESCs and adult stem/progenitor cells. A large
      number of these genes are key developmental regulators, and a subset, which we
      call the "DNA hypermethylation module," comprises a portion of the PcG target
      genes that are down-regulated in cancer. Genes with bivalent chromatin have a
      low, poised gene transcription state that has been shown to maintain stemness and
      self-renewal in normal stem cells. However, when DNA-hypermethylated in tumors,
      we find that these genes are further repressed. We also show that the methylation
      status of these genes can cluster important subtypes of colon and breast cancers.
      By evaluating the subsets of genes that are methylated in different cancers with
      consideration of their chromatin status in ESCs, we provide evidence that DNA
      hypermethylation preferentially targets the subset of PcG genes that are
      developmental regulators, and this may contribute to the stem-like state of
      cancer. Additionally, the capacity for global methylation profiling to cluster
      tumors by phenotype may have important implications for further refining tumor
      behavior patterns that may ultimately aid therapeutic interventions.

PMID- 22391557
TI  - Transcriptome survey reveals increased complexity of the alternative splicing
      landscape in Arabidopsis.
AB  - Alternative splicing (AS) is a key regulatory mechanism that contributes to
      transcriptome and proteome diversity. As very few genome-wide studies analyzing
      AS in plants are available, we have performed high-throughput sequencing of a
      normalized cDNA library which resulted in a high coverage transcriptome map of
      Arabidopsis. We detect ~150,000 splice junctions derived mostly from typical
      plant introns, including an eightfold increase in the number of U12 introns
      (2069). Around 61% of multiexonic genes are alternatively spliced under normal
      growth conditions. Moreover, we provide experimental validation of 540 AS
      transcripts (from 256 genes coding for important regulatory factors) using high
      resolution RT-PCR and Sanger sequencing. Intron retention (IR) is the most
      frequent AS event (~40%), but many IRs have relatively low read coverage and are
      less well-represented in assembled transcripts. Additionally, ~51% of Arabidopsis
      genes produce AS transcripts which do not involve IR. Therefore, the significance
      of IR in generating transcript diversity was generally overestimated in previous
      assessments. IR analysis allowed the identification of a large set of cryptic
      introns inside annotated coding exons. Importantly, a significant fraction of
      these cryptic introns are spliced out in frame, indicating a role in protein
      diversity. Furthermore, we show extensive AS coupled to nonsense-mediated decay
      in AFC2, encoding a highly conserved LAMMER kinase which phosphorylates splicing
      factors, thus establishing a complex loop in AS regulation. We provide the most
      comprehensive analysis of AS to date which will serve as a valuable resource for
      the plant community to study transcriptome complexity and gene regulation.

PMID- 22391558
TI  - Tumor development is associated with decrease of TET gene expression and 5
      methylcytosine hydroxylation.
AB  - The TET (ten-eleven translocation) family of alpha-ketoglutarate (alpha-KG)
      dependent dioxygenases catalyzes the sequential oxidation of 5-methylcytosine
      (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine,
      leading to eventual DNA demethylation. The TET2 gene is a bona fide tumor
      suppressor frequently mutated in leukemia, and TET enzyme activity is inhibited
      in IDH1/2-mutated tumors by the oncometabolite 2-hydroxyglutarate, an antagonist
      of alpha-KG, linking 5mC oxidation to cancer development. We report here that the
      levels of 5hmC are dramatically reduced in human breast, liver, lung, pancreatic
      and prostate cancers when compared with the matched surrounding normal tissues.
      Associated with the 5hmC decrease is the substantial reduction of the expression
      of all three TET genes, revealing a possible mechanism for the reduced 5hmC in
      cancer cells. The decrease of 5hmC was also observed during tumor development in
      different genetically engineered mouse models. Together, our results identify
      5hmC as a biomarker whose decrease is broadly and tightly associated with tumor
      development.

PMID- 22391559
TI  - Ribosomal protein S14 unties the MDM2-p53 loop upon ribosomal stress.
AB  - The MDM2-p53 feedback loop is crucially important for restricting p53 level and
      activity during normal cell growth and proliferation, and is thus subjected to
      dynamic regulation in order for cells to activate p53 upon various stress
      signals. Several ribosomal proteins, such as RPL11, RPL5, RPL23, RPL26 or RPS7,
      have been shown to have a role in regulation of this feedback loop in response to
      ribosomal stress. Here, we identify another ribosomal protein S14, which is
      highly associated with 5q-syndrome, as a novel activator of p53 by inhibiting
      MDM2 activity. We found that RPS14, but not RPS19, binds to the central acidic
      domain of MDM2, similar to RPL5 and RPL23, and inhibits its E3 ubiquitin ligase
      activity toward p53. This RPS14-MDM2 binding was induced upon ribosomal stress
      caused by actinomycin D or mycophenolic acid. Overexpression of RPS14, but not
      RPS19, elevated p53 level and activity, leading to G1 or G2 arrest. Conversely,
      knockdown of RPS14 alleviated p53 induction by these two reagents. Interestingly,
      knockdown of either RPS14 or RPS19 caused a ribosomal stress that led to p53
      activation, which was impaired by further knocking down the level of RPL11 or
      RPL5. Together, our results demonstrate that RPS14 and RPS19 have distinct roles
      in regulating the MDM2-p53 feedback loop in response to ribosomal stress.

PMID- 22391561
TI  - Tumor angiogenesis is enforced by autocrine regulation of high-mobility group box
      1.
AB  - The endothelium plays a pivotal role in the progression of solid tumors and is
      considered a highly relevant target for therapy. However, it emerges that current
      clinical angiogenesis inhibitors that act through inhibition of tumor-derived
      growth factors are prone to inducing drug resistance. Therefore, markers of tumor
      endothelial cells (ECs) themselves provide attractive novel therapeutic targets.
      In a screen for markers of tumor angiogenesis, we recently identified high
      mobility group box 1 (HMGB1), known to act as proinflammatory cytokine and
      chromatin-binding molecule. Here we report on the role of HMGB1 in angiogenesis
      by showing that its overexpression is associated with an increased angiogenic
      potential of ECs. HMGB1 stimulates the expression of players in vascular
      endothelial growth factor and platelet-derived growth factor signaling, both in
      vitro and in vivo. Importantly, we show that HMGB1 triggers and helps to sustain
      this proangiogenic gene expression program in ECs, additionally characterized by
      increased activity of matrix metalloproteinases, integrins and nuclear factor
      kappaB. Moreover, we found that HMGB1 is involved in several autocrine and/or
      paracrine feedback mechanisms resulting in positive enforcement of HMGB1
      expression, and that of its receptors, RAGE (receptor for advanced glycation end
      products) and Toll-like receptor 4 (TLR4). Interference in HMGB1 expression
      and/or function using knockdown approaches and antibody-mediated targeting to
      break this vicious circle resulted in inhibited migration and sprouting of ECs.
      Using different in vivo models, therapeutic efficacy of HMGB1 targeting was
      confirmed. First, we demonstrated induction of HMGB1 expression in the chicken
      embryo chorioallantoic membrane (CAM) neovasculature following both photodynamic
      therapy and tumor challenge. We subsequently showed that anti-HMGB1 antibodies
      inhibited vessel density in both models, accompanied by a reduced vascular
      expression of angiogenic growth factor receptors. Collectively, these data
      identify HMGB1 as an important modulator of tumor angiogenesis and suggest the
      feasibility of targeting HMGB1 for multi-level cancer treatment.

PMID- 22391560
TI  - UVB-induced COX-2 expression requires histone H3 phosphorylation at Ser10 and
      Ser28.
AB  - Cyclooxygenase-2 (COX-2) is an inducible enzyme that contributes to the
      generation of chronic inflammation in response to chemical carcinogens and
      environmental stresses, including ultraviolet B (UVB) irradiation. Although post
      translational histone modifications are believed to have an important role in
      modulating transcriptional regulation of UVB-induced COX-2, the underlying
      biochemical mechanisms are completely unknown. Here, we show that UVB activates
      the p38 MAPK/MSK1 kinase cascade to phosphorylate histone H3 at Ser10 and Ser28,
      contributing to UVB-induced COX-2 expression. UVB has no effect on the global tri
      methylation level of histone H3 (H3K4me3, H3K9me3, and H3K27me3). We observed
      that selected mammalian 14-3-3 proteins bind to UVB-induced phosphorylated
      histone H3 (Ser10 and Ser28). In particular, 14-3-3E is critical for recruiting
      MSK1 and Cdk9 to the chromatin and subsequently phosphorylating the C-terminal
      domain of RNA polymerase II in the cox-2 promoter. We propose that histone H3
      phosphorylation at Ser10 and Ser28 serve as critical switches to promote cox-2
      gene expression by facilitating the recruitment of MSK1 and Cdk9 to the cox-2
      promoter, thereby promoting RNA polymerase II phosphorylation.

PMID- 22391562
TI  - A potent Chk1 inhibitor is selectively cytotoxic in melanomas with high levels of
      replicative stress.
AB  - There are few effective treatments for metastatic melanoma. Checkpoint kinase 1
      (Chk1) inhibitors are being trialled for their efficacy in enhancing conventional
      chemotherapeutic agents, but their effectiveness as single agents is not known.
      We have examined the effectiveness of two novel Chk1 selective inhibitors, AR323
      and AR678, in a panel of melanoma cell lines and normal cell types. We
      demonstrate that these drugs display single-agent activity, with IC50s in the low
      nanomolar range. The drugs produce cytotoxic effects in cell lines that are most
      sensitive to these drugs, whereas normal cells are only sensitive to these drugs
      at the higher concentrations where they have cytostatic activity. The cytotoxic
      effect is the consequence of inhibition of S-phase Chk1, which drives cells
      prematurely from late S phase into an aberrant mitosis and results in either
      failure of cytokinesis or cell death through an apoptotic mechanism. The
      sensitivity to the Chk1 inhibitors was correlated with the level of endogenous
      DNA damage indicating replicative stress. Chk1 inhibitors are viable single-agent
      therapies that target melanoma cells with high levels of endogenous DNA damage.
      This sensitivity suggests that Chk1 is a critical component of an adaptation to
      replicative stress in these cells. It also suggests that markers of DNA damage
      may be useful in identifying the melanomas and potentially other tumour types
      that are more likely to be sensitive to Chk1 inhibitors as single agents.

PMID- 22391563
TI  - The deubiquitination enzyme USP46 functions as a tumor suppressor by controlling
      PHLPP-dependent attenuation of Akt signaling in colon cancer.
AB  - PH domain leucine-rich-repeats protein phosphatase (PHLPP) is a family of Ser/Thr
      protein phosphatases that serve as tumor suppressors by negatively regulating
      Akt. Our recent studies have demonstrated that the ubiquitin proteasome pathway
      has an important role in the downregulation of PHLPP in colorectal cancer. In
      this study, we show that the deubiquitinase USP46 stabilizes the expression of
      both PHLPP isoforms by reducing the rate of PHLPP degradation. USP46 binds to
      PHLPP and directly removes the polyubiquitin chains from PHLPP in vitro and in
      cells. Increased USP46 expression correlates with decreased ubiquitination and
      upregulation of PHLPP proteins in colon cancer cells, whereas knockdown of USP46
      has the opposite effect. Functionally, USP46-mediated stabilization of PHLPP and
      the subsequent inhibition of Akt result in a decrease in cell proliferation and
      tumorigenesis of colon cancer cells in vivo. Moreover, reduced USP46 protein
      level is found associated with poor PHLPP expression in colorectal cancer patient
      specimens. Taken together, these results indentify a tumor suppressor role of
      USP46 in promoting PHLPP expression and inhibiting Akt signaling in colon cancer.

PMID- 22391564
TI  - MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are
      downregulated in prostate carcinoma.
AB  - With ~30 000 deaths annually in the United States, prostate cancer (PCa) is a
      major oncologic disease. Here we show that the microRNAs miR-130a, miR-203 and
      miR-205 jointly interfere with the two major oncogenic pathways in prostate
      carcinoma and are downregulated in cancer tissue. Using transcriptomics we show
      that the microRNAs repress several gene products known to be overexpressed in
      this cancer. Argonaute 2 (AGO2) co-immunoprecipitation, reporter assays and
      western blot analysis demonstrate that the microRNAs directly target several
      components of the mitogen-activated protein kinase (MAPK) and androgen receptor
      (AR) signaling pathways, among those several AR coregulators and HRAS (Harvey rat
      sarcoma viral oncogene homolog), and repress signaling activity. Both pathways
      are central for the development of the primary tumor and in particular the
      progression to its incurable castration-resistant form. Reconstitution of the
      microRNAs in LNCaP PCa cells induce morphological changes, which resemble the
      effect of androgen deprivation, and jointly impair tumor cell growth by induction
      of apoptosis and cell cycle arrest. We therefore propose that these microRNAs
      jointly act as tumor suppressors in prostate carcinoma and might interfere with
      progression to castration resistance.

PMID- 22391565
TI  - Low dose IR-induced IGF-1-sCLU expression: a p53-repressed expression cascade
      that interferes with TGFbeta1 signaling to confer a pro-survival bystander
      effect.
AB  - Inadvertent mammalian tissue exposures to low doses of ionizing radiation (IR)
      after radiation accidents, remediation of radioactive-contaminated areas, space
      travel or a dirty bomb represent an interesting trauma to an organism. Possible
      low-dose IR-induced bystander effects could impact our evaluation of human health
      effects, as cells within tissue are not equally damaged after doses of IR <=10
      cGy. To understand tissue responses after low IR doses, we generated a reporter
      system using the human clusterin promoter fused to firefly luciferase (hCLUp
      Luc). Secretory clusterin (sCLU), an extracellular molecular chaperone, induced
      by low doses of cytotoxic agents, clears cell debris. Low-dose IR (>=2 cGy)
      exposure induced hCLUp-Luc activity with peak levels at 96 h, consistent with
      endogenous sCLU levels. As doses increased (>=1 Gy), sCLU induction amplitudes
      increased and time-to-peak response decreased. sCLU expression was stimulated by
      insulin-like growth factor-1, but suppressed by p53. Responses in transgenic
      hCLUp-Luc reporter mice after low IR doses showed that specific tissues (that is,
      colon, spleen, mammary, thymus and bone marrow) of female mice induced hCLUp-Luc
      activity more than male mice after whole body (>=10 cGy) irradiation. Tissue
      specific, non-linear dose- and time-responses of hCLUp-Luc and endogenous sCLU
      levels were noted. Colon maintained homeostatic balance after 10 cGy. Bone marrow
      responded with delayed, but prolonged and elevated expression. Intraperitoneal
      administration of alpha-transforming growth factor (TGF)beta1 (1D11), but not
      control (13C4) antibodies, immediately following IR exposure abrogated CLU
      induction responses. Induction in vivo also correlated with Smad signaling by
      activated TGFbeta1 after IR. Mechanistically, media with elevated sCLU levels
      suppressed signaling, blocked apoptosis and increased survival of TGFbeta1
      exposed tumor or normal cells. Thus, sCLU is a pro-survival bystander factor that
      abrogates TGFbeta1 signaling and most likely promotes wound healing.

PMID- 22391566
TI  - EpCAM regulates cell cycle progression via control of cyclin D1 expression.
AB  - The epithelial cell adhesion molecule (EpCAM) is an integral transmembrane
      protein that is frequently overexpressed in embryonic stem cells, tissue
      progenitors, carcinomas and cancer-initiating cells. In cancer cells, expression
      of EpCAM is associated with enhanced proliferation and upregulation of target
      genes including c-myc. However, the exact molecular mechanisms underlying the
      observed EpCAM-dependent cell proliferation remained unexplored. Here, we show
      that EpCAM directly affects cell cycle progression via its capacity to regulate
      the expression of cyclin D1 at the transcriptional level and depending on the
      direct interaction partner FHL2 (four-and-a-half LIM domains protein 2). As a
      result, downstream events such as phosphorylation of the retinoblastoma protein
      (Rb) and expression of cyclins E and A are similarly affected. In vivo, EpCAM
      expression strength and pattern are both positively correlated with the
      proliferation marker Ki67, high expression and nuclear localisation of cyclin D1,
      and Rb phosphorylation. Thus, EpCAM enhances cell cycle progression via the
      classical cyclin-regulated pathway.

PMID- 22391567
TI  - FOXA1 represses the molecular phenotype of basal breast cancer cells.
AB  - Breast cancer is a heterogeneous disease that comprises multiple subtypes.
      Luminal subtype tumors confer a more favorable patient prognosis, which is, in
      part, attributed to estrogen receptor (ER)-alpha positivity and antihormone
      responsiveness. Expression of the forkhead box transcription factor, FOXA1,
      similarly correlates with the luminal subtype and patient survival, but is also
      present in a subset of ER-negative tumors. FOXA1 is also consistently expressed
      in luminal breast cancer cell lines even in the absence of ER. In contrast,
      breast cancer cell lines representing the basal subtype do not express FOXA1. To
      delineate an ER-independent role for FOXA1 in maintaining the luminal phenotype,
      and hence a more favorable prognosis, we performed expression microarray analyses
      on FOXA1-positive and ER-positive (MCF7, T47D), or FOXA1-positive and ER-negative
      (MDA-MB-453, SKBR3) luminal cell lines in the presence or absence of transient
      FOXA1 silencing. This resulted in three FOXA1 transcriptomes: (1) a luminal
      signature (consistent across cell lines), (2) an ER-positive signature
      (restricted to MCF7 and T47D) and (3) an ER-negative signature (restricted to MDA
      MB-453 and SKBR3). Gene set enrichment analyses revealed FOXA1 silencing causes a
      partial transcriptome shift from luminal to basal gene expression signatures.
      FOXA1 binds to a subset of both luminal and basal genes within luminal breast
      cancer cells, and loss of FOXA1 increases enhancer RNA transcription for a
      representative basal gene (CD58). These data suggest FOXA1 directly represses a
      subset of basal signature genes. Functionally, FOXA1 silencing increases
      migration and invasion of luminal cancer cells, both of which are characteristics
      of basal subtype cells. We conclude FOXA1 controls plasticity between basal and
      luminal breast cancer cells, not only by inducing luminal genes but also by
      repressing the basal phenotype, and thus aggressiveness. Although it has been
      proposed that FOXA1-targeting agents may be useful for treating luminal tumors,
      these data suggest that this approach may promote transitions toward more
      aggressive cancers.

PMID- 22391568
TI  - Histone deacetylase inhibitors suppress mutant p53 transcription via histone
      deacetylase 8.
AB  - Mutation of the p53 gene is the most common genetic alteration in human cancer
      and contributes to malignant process by enhancing transformed properties of cells
      and resistance to anticancer therapy. Mutant p53 is often highly expressed in
      tumor cells at least, in part, due to its increased half-life. However, whether
      mutant p53 expression is regulated by other mechanisms in tumors is unclear. Here
      we found that histone deacetylase (HDAC) inhibitors suppress both wild-type and
      mutant p53 transcription in time- and dose-dependent manners. Consistent with
      this, the levels of wild-type and mutant p53 proteins are decreased upon
      treatment with HDAC inhibitors. Importantly, we found that upon knockdown of each
      class I HDAC, only HDAC8 knockdown leads to decreased expression of wild-type and
      mutant p53 proteins and transcripts. Conversely, we found that ectopic expression
      of wild-type, but not mutant HDAC8, leads to increased transcription of p53.
      Furthermore, we found that knockdown of HDAC8 results in reduced expression of
      HoxA5 and consequently, attenuated ability of HoxA5 to activate p53
      transcription, which can be rescued by ectopic expression of HoxA5. Because of
      the fact that HDAC8 is required for expression of both wild-type and mutant p53,
      we found that targeted disruption of HDAC8 expression remarkably triggers
      proliferative defect in cells with a mutant, but not wild-type, p53. Together,
      our data uncover a regulatory mechanism of mutant p53 transcription via HDAC8 and
      suggest that HDAC inhibitors and especially HDAC8-targeting agents might be
      explored as an adjuvant for tumors carrying a mutant p53.

PMID- 22391569
TI  - microRNA-125b inhibits tube formation of blood vessels through translational
      suppression of VE-cadherin.
AB  - Angiogenesis is controlled positively or negatively by extrinsic and intrinsic
      molecular cues in endothelial cells (ECs); in the tumor microenvironment, the
      action of positive regulators exceeds that of negative regulators. Thus,
      overinduction of negative regulators may inhibit tumor angiogenesis. MicroRNAs
      (miRNAs or miRs) are endogenous short noncoding RNAs regulating gene expression
      either through translational inhibition or destabilization of target mRNA. Here,
      we show that miR-125b expression is transiently induced in ECs on stimulation
      with vascular endothelial growth factor or by ischemia. miR-125b inhibits
      translation of vascular endothelial (VE)-cadherin mRNA and in vitro tube
      formation by ECs. Injection of miR-125b into the tumor inhibited VE-cadherin
      expression by ECs and induced nonfunctional blood vessel formation, resulting in
      inhibition of tumor growth. It has been suggested that pro-angiogenic signals in
      ECs also upregulate anti-angiogenic molecules simultaneously via negative
      feedback. Because miR-125b induction in ECs is transient after pro-angiogenic
      stimulation, prolonged overexpression of miR-125b could result in blood vessel
      regression. Thus, miR-125b may be useful in cancer therapy by causing the
      collapse of the lumen of ECs.

PMID- 22391571
TI  - Protein N-terminal acetyltransferases in cancer.
AB  - The human N-terminal acetyltransferases (NATs) catalyze the transfer of acetyl
      moieties to the N-termini of 80-90% of all human proteins. Six NAT types are
      present in humans, NatA-NatF, each is composed of specific subunits and each
      acetylates a set of substrates defined by the N-terminal amino-acid sequence.
      NATs have been suggested to act as oncoproteins as well as tumor suppressors in
      human cancers, and NAT expression may be both elevated and decreased in cancer
      versus non-cancer tissues. Manipulation of NATs in cancer cells induced cell
      cycle arrest, apoptosis or autophagy, implying that these enzymes target a
      variety of pathways. Of particular interest is hNaa10p (human ARD1), the
      catalytic subunit of the NatA complex, which was coupled to a number of signaling
      molecules including hypoxia inducible factor-1alpha, beta-catenin/cyclin D1,
      TSC2/mammalian target of rapamycin, myosin light chain kinase , DNA
      methyltransferase1/E-cadherin and p21-activated kinase-interacting exchange
      factors (PIX)/Cdc42/Rac1. The variety of mechanistic links where hNaa10p acts as
      a NAT, a lysine acetyltransferase or displaying a non-catalytic role, provide
      insights to how hNaa10p may act as both a tumor suppressor and oncoprotein.

PMID- 22391570
TI  - S6K1 determines the metabolic requirements for BCR-ABL survival.
AB  - In chronic myelogenous leukemia, the constitutive activation of the BCR-ABL
      kinase transforms cells to an addicted state that requires glucose metabolism for
      survival. We investigated S6K1, a protein kinase that drives glycolysis in
      leukemia cells, as a target for counteracting glucose-dependent survival induced
      by BCR-ABL. BCR-ABL potently activated S6K1-dependent signaling and glycolysis.
      Although S6K1 knockdown or rapamycin treatment suppressed glycolysis in BCR-ABL
      transformed cells, these treatments did not induce cell death. Instead, loss of
      S6K1 triggered compensatory activation of fatty-acid oxidation, a metabolic
      program that can support glucose-independent cell survival. Fatty-acid oxidation
      in response to S6K1 inactivation required the expression of the fatty-acid
      transporter carnitine palmitoyl transferase 1c, which was recently linked to
      rapamycin resistance in cancer. Finally, addition of an inhibitor of fatty-acid
      oxidation significantly enhanced cytotoxicity in response to S6K1 inactivation.
      These data indicate that S6K1 dictates the metabolic requirements mediating BCR
      ABL survival and provide a rationale for combining targeted inhibitors of signal
      transduction, with strategies to interrupt oncogene-induced metabolism.

PMID- 22391573
TI  - On the stability of an unsupported mercury-mercury bond linking group 15 Zintl
      clusters.
AB  - The dimeric Zintl ion [Hg(2)(As(7))(2)](4-) has been synthesized with high
      crystalline yield from the reaction of an ethylendiamine solution of the
      intermetallic Zintl phase K(3)As(7) with diphenyl mercury. Single crystal X-ray
      diffraction of [K(2,2,2-crypt)](4)[Hg(2)As(14)], 1 (2,2,2-crypt = 4,7,13,16,21,24
      hexaoxa-1,10-diazabicyclo[8.8.8]-hexacosane), reveals that the cluster anion
      exhibits a Hg-Hg bond and the compound has been further characterized using Raman
      spectroscopy, cyclic voltammetry and its band gap energy was measured.
      Theoretical studies provide a microscopic understanding of the bonding in this
      unusual compound.

PMID- 22391572
TI  - Increased invasiveness of MMP-9-deficient tumors in two mouse models of
      neuroendocrine tumorigenesis.
AB  - Despite their apparent success in pre-clinical trials, metalloproteinase (MMP)
      inhibitors proved to be inefficacious in clinical settings. In an effort to
      understand the underlying causes of this unanticipated outcome, we modeled the
      consequences of long-term MMP inhibition by removing one of the major players in
      tumorigenesis, MMP9, in two complimentary mouse models of pancreatic
      neuroendocrine carcinogenesis: Myc;BclXl and RIP1-Tag2. By employing gel
      zymography and a fluoregenic solution assay, we first established that MMP9 is
      expressed and activated in Myc;BclXl tumors in an interleukin-1beta-dependent
      manner. The genetic deletion of MMP9 in Myc;BclXl mice impairs tumor angiogenesis
      and growth analogous to its absence in the RIP1-Tag2 model. Notably, tumors that
      developed in the context of MMP9-deficient backgrounds in both models were
      markedly more invasive than their typical wild-type counterparts, and expressed
      elevated levels of pro-invasive cysteine cathepsin B. The increased invasion of
      MMP9-deficient tumors was associated with a switch in the spectrum of
      inflammatory cells at the tumor margins, involving homing of previously
      undetected, cathepsin-B expressing CD11b;Gr1-positive cells to the invasive
      fronts. Thus, plasticity in the tumor inflammatory compartment is partially
      responsible for changes in the expression pattern of tumor-associated proteases,
      and may contribute to the compensatory effects observed on MMP inhibition, hence
      accounting for the heightened tumor progression described in late stage clinical
      trials.

PMID- 22391574
TI  - Sunitinib targets PDGF-receptor and Flt3 and reduces survival and migration of
      human meningioma cells.
AB  - The multitargeted tyrosine-kinase inhibitor sunitinib is a highly effective anti
      angiogenic and cytostatic agent in the therapy of various tumours. While
      malignant gliomas have been shown to be responsive to sunitinib, detailed studies
      analysing human meningiomas are missing. We therefore analysed the effects of
      sunitinib in two benign (BenMen-1, HBL52) and two malignant (IOMM-Lee, KT21MG)
      human meningioma cell lines and found that DNA synthesis was significantly (p <=
      0.001) inhibited following 1, 2 or 5 MUM sunitinib, with IC(50) values between 2
      and 5 MUM in all cell lines. This effect was associated with a G(2)M-arrest at 10
      MUM for BenMen-1, HBL52 and IOMM-Lee, and 20 MUM in KT21MG cells. Nuclear
      bisbenzimide staining revealed chromatin condensation following treatment with
      sunitinib concentrations of 10 MUM or higher. Corresponding, cell viability
      assays showed a significant (p <= 0.001) short term decrease of viable cells
      (24h) only for high sunitinib concentrations with IC(50)-values between 10 and 20
      MUM. However, pre-irradiated meningioma cells (5 Gy) showed a sensitivity shift
      towards IC(50)-values around 5 MUM sunitinib. We also found that 5 MUM strongly
      reduced meningioma cell migration in vitro. Western blot analyses showed
      abolished platelet derived growth factor receptor (PDGFR)-autophosphorylation
      after sunitinib. Interestingly, the drug also inhibited the autophosphorylation
      of the receptor tyrosine kinase fms-like tyrosine kinase 3 (Flt3) in a dose
      dependent manner. Taken together, the present data show that micromolar sunitinib
      has strong cytostatic and anti-migratory effects on human meningioma cells.

PMID- 22391575
TI  - Prospective association between body mass index and receipt of preventive
      services: results from the Central Pennsylvania Women's Health Study (CePAWHS).
AB  - OBJECTIVE: We examine whether overweight and obesity are associated with
      disparities in clinical preventive services receipt in a unique, prospective,
      population-based cohort of reproductive-age women. METHOD: We used data from the
      Central Pennsylvania Women's Health Study (CePAWHS) longitudinal survey of women
      ages 18-45. The baseline random-digit-dial telephone survey was conducted in 2004
      2005 and a second telephone interview two years later; 1342 participants
      comprised the analytic sample. Dependent variables were seven preventive services
      identified at follow-up. In addition to baseline body mass index (BMI) category,
      independent variables were selected based on the behavioral model of health
      services utilization. RESULTS: Forty-six percent of the sample was classified as
      normal weight, 28% as overweight, and 26% as obese. In adjusted analyses, women
      who were overweight and obese, compared to women with normal weight, were more
      likely to receive preventive counseling for diet/nutrition, physical activity,
      and weight management (p<0.01). Overweight and obese women received more
      cholesterol and diabetes screening (p<0.05 and p<0.01, respectively). However,
      there were no differences by BMI category in receipt of Pap testing or
      reproductive counseling. CONCLUSION: Overall, we found that women with overweight
      and obesity were more likely to receive preventive services, especially services
      relevant for overweight and obese populations.

PMID- 22391576
TI  - Applying the concept of culture to reduce health disparities through health
      behavior research.
AB  - Culture is often cited as an underlying cause of the undue burden of disease
      borne by communities of color along the entire life cycle. However, culture is
      rarely defined or appropriately measured. Scientifically, culture is a complex,
      integrated, and dynamic conceptual framework that is incongruent with the way it
      is operationalized in health behavior theories: as a unidimensional, static, and
      immutable character element of a homogeneous population group. This paper lays
      out this contradiction and proposes a more scientifically grounded approach to
      the use of culture. The premise is that if the concept of culture were better
      operationalized, results from studies of diverse population groups would produce
      findings that are more scientifically valid and relevant to the community.
      Practitioners could then use these findings to develop more effective strategies
      to reduce health disparities and improve the health of all population groups. Six
      steps are proposed to increase our ability to achieve greater clarity on what
      culture is and to identify how it impacts health behavior and ultimately health
      outcomes, enabling researchers to build a stronger science of cultural diversity.

PMID- 22391577
TI  - Human CD55 expression blocks hyperacute rejection and restricts complement
      activation in Gal knockout cardiac xenografts.
AB  - BACKGROUND: Transgenic expression of human complement regulatory proteins reduces
      the frequency of hyperacute rejection (HAR) in Gal-positive cardiac
      xenotransplantation. In this study, we examined the impact of human CD55 (hCD55)
      expression on a Gal knockout (GTKO) background using pig-to-primate heterotopic
      cardiac xenotransplantation. METHODS: Cardiac xenotransplantation was performed
      with GTKO (group 1; n=6) and GTKO.hCD55 (group 2; n=5) donor pigs using similar
      immunosuppression. Cardiac biopsies were obtained 30 min after organ reperfusion.
      Rejection was characterized by histology and immunohistology. Intragraft gene
      expression, serum non-Gal antibody, and antibody recovered from rejected hearts
      were analyzed. RESULTS: HAR of a GTKO heart was observed. Remaining grafts
      developed delayed xenograft rejection. Median survival was 21 and 28 days for
      groups 1 and 2, respectively. Vascular antibody deposition was uniformly detected
      30 min after organ reperfusion and at explant. A higher frequency of vascular C5b
      deposition was seen in GTKO organs at explant. Serum non-Gal antibody, antibody
      recovered from the graft, and intragraft gene expression were similar between the
      groups. CONCLUSION: HAR of GTKO hearts without hCD55 may occur. Expression of
      hCD55 seemed to restrict local complement activation but did not improve graft
      survival. Chronic vascular antibody deposition with evidence of protracted
      endothelial cell activation was seen. These observations suggest that non-Gal
      antibody-induced chronic endothelial cell activation coupled to possible
      hemostatic incompatibilities may be the primary stimulus for delayed xenograft
      rejection of GTKO hearts. To avoid possible HAR, future clinical studies should
      use donors expressing human complement regulatory proteins in the GTKO
      background.

PMID- 22391578
TI  - Substituted oxines inhibit endothelial cell proliferation and angiogenesis.
AB  - Two substituted oxines, nitroxoline (5) and 5-chloroquinolin-8-yl phenylcarbamate
      (22), were identified as hits in a high-throughput screen aimed at finding new
      anti-angiogenic agents. In a previous study, we have elucidated the molecular
      mechanism of antiproliferative activity of nitroxoline in endothelial cells,
      which comprises of a dual inhibition of type 2 human methionine aminopeptidase
      (MetAP2) and sirtuin 1 (SIRT1). Structure-activity relationship study (SAR) of
      nitroxoline offered many surprises where minor modifications yielded oxine
      derivatives with increased potency against human umbilical vein endothelial cells
      (HUVEC), but with entirely different as yet unknown mechanisms. For example, 5
      nitrosoquinolin-8-ol (33) inhibited HUVEC growth with sub-micromolar IC(50), but
      did not affect MetAP2 or MetAP1, and it only showed weak inhibition against
      SIRT1. Other sub-micromolar inhibitors were derivatives of 5-aminoquinolin-8-ol
      (34) and 8-sulfonamidoquinoline (32). A sulfamate derivative of nitroxoline (48)
      was found to be more potent than nitroxoline with the retention of activities
      against MetAP2 and SIRT1. The bioactivity of the second hit, micromolar HUVEC and
      MetAP2 inhibitor carbamate 22 was improved further with an SAR study culminating
      in carbamate 24 which is a nanomolar inhibitor of HUVEC and MetAP2.

PMID- 22391579
TI  - Differential expression of potassium channels in placentas from normal and
      pathological pregnancies: targeting of the K(ir) 2.1 channel to lipid rafts.
AB  - Potassium channels play important physiological roles in human
      syncytiotrophoblasts (hSTBs) from placenta, an epithelium responsible for
      maternal-fetal exchange. Basal and apical plasma membranes differ in their lipid
      and protein composition, and the latter contains cholesterol-enriched
      microdomains. In placental tissue, the specific localization of potassium
      channels is unknown. Previously, we described two isolated subdomains from the
      apical membrane (MVM and LMVM) and their respective microdomains (lipid rafts).
      Here, we report on the distribution of K(ir)2.1, K(v)2.1, TASK-1, and TREK-1 in
      hSTB membranes and the lipid rafts that segregate them. Immunoblotting
      experiments showed that these channels are present mainly in the apical membrane
      from healthy hSTBs. Apical expression versus basal membrane was 84 and 16% for
      K(ir)2.1 and K(v)2.1, 60 and 30% for TREK-1, and 74 and 26% for TASK-1.
      Interestingly, K(v)2.1 showed differences between apical membrane subdomains: 26
      +/- 8% was located in the LMVM and 59 +/- 9% in MVM. In pathological placentas,
      the expression distribution changed in the basal membrane: preeclampsia shifted
      to 50% and intrauterine growth restriction to 42% for TASK-1 and both pathologies
      increased to 25% for K(ir)2.1 and K(v)2.1, K(ir)2.1 appeared to be associated
      with rafts that were sensitive to cholesterol depletion in healthy, but not in
      pathological, placentas. K(v)2.1 and TREK-1 emerged in the nonraft fractions. The
      precise membrane localization of ion channels in hSTB membranes is necessary to
      understand the physiological events.

PMID- 22391580
TI  - Endothelial keratoplasty without Descemet stripping after failed penetrating
      keratoplasty.
AB  - PURPOSE: To evaluate outcomes of endothelial keratoplasty (EK) without Descemet
      membrane stripping for treatment of failed penetrating keratoplasty (PKP).
      METHODS: Retrospective cohort study of all eyes that underwent EK without
      Descemet membrane stripping for failed PKP at one institution between May 2008
      and June 2010, with follow-up to 12 months. Main outcome measures were best
      corrected visual acuity (BCVA), dislocation rate, and graft failure. RESULTS:
      Twenty-two eyes of 22 patients underwent non-Descemet stripping EK with a mean
      follow-up of 8.8 months (+/-3.41; range, 3-12 months). The mean preoperative BCVA
      was logarithm of the minimum angle of resolution (logMAR) 1.43 (+/-0.72; range,
      0.3-3; Snellen, 20/537; N = 22). The mean postoperative BCVA was logMAR 0.97 (+/
      0.88; range, 0-3; N = 21) at 1 month, 0.76 logMAR (+/-0.74; range, 0.1-3; N = 21)
      at 3 months, 0.75 (+/-0.77; range, 0-3; N = 17) at 6 months, and logMAR 0.55 (+/
      0.38; range, 0.18-1; Snellen, 20/70; N = 9) at 1 year. Eight eyes (36.6%) had
      graft dislocations requiring one rebubbling procedure in 6 of 8 eyes and 2
      rebubblings in the other 2 eyes. All grafts were successfully reattached. Graft
      failure occurred in 2 of 22 eyes (9%), with 1 eye (5%) undergoing repeat EK and 1
      eye (5%) undergoing PKP. CONCLUSIONS: EK without Descemet membrane stripping is
      an effective option for management of eyes with failed PKP and may be a
      preferable alternative to a repeat PKP.

PMID- 22391581
TI  - Risk of stroke after transcatheter aortic valve implantation (TAVI): a meta
      analysis of 10,037 published patients.
AB  - AIMS: Transcatheter aortic valve implantation (TAVI) represents a novel treatment
      option for inoperable or high surgical risk patients with severe symptomatic
      aortic valve disease. Recent randomised studies have raised major safety concerns
      because of increased stroke/transient ischemic attack (TIA) rates with TAVI
      compared to medical treatment and conventional aortic valve replacement. We aimed
      to review all currently published literature and estimate the incidence of
      periprocedural stroke and outcomes in patients undergoing TAVI. METHODS AND
      RESULTS: Fifty-three studies including a total of 10,037 patients undergoing
      transfemoral, transapical or trans-subclavian TAVI for native aortic valve
      stenosis published between 01/2004 and 11/2011 were identified and included in a
      meta-analysis. Patients were 81.5 +/- 1.8-years-old and had a mean logistic
      EuroSCORE of 24.77 +/- 5.60%. Procedural stroke (<24 h) occurred in 1.5 +/- 1.4%.
      The overall 30-day stroke/TIA was 3.3 +/- 1.8%, with the majority being major
      strokes (2.9 +/- 1.8%). During the first year after TAVI, stroke/TIA increased up
      to 5.2 +/- 3.4%. Differences in stroke rates were associated with different
      approaches and valve prostheses used with lowest stroke rates after transapical
      TAVI (2.7 +/- 1.4%). Average 30-day mortality was more than 3.5-fold higher in
      patients with compared to those without stroke (25.5 +/- 21.9% vs. 6.9 +/- 4.2%).
      CONCLUSIONS: TAVI was associated with average 30-day stroke/TIA rate of 3.3 +/-
      1.8% (range 0-6%). Most of these strokes were major strokes and were associated
      with increased mortality within in the first 30 days.

PMID- 22391582
TI  - In situ selective N-alkylation of pendant pyridyl functionality in mixed-valence
      copper complexes with methanol and copper(II) bromide.
AB  - The reactions of CuBr(2) with pyridyl 2,2':6',2''-terpyridine ligands in methanol
      yielded four copper complexes under solvothermal conditions. The self-assembly
      processes were accompanied by designing bitopic precursor ligands and increasing
      the stoichiometric metal-ligand ratio. In the four resulting complexes, the
      pendant pyridyl groups of pyridylterpyridine were selectively in situ N
      methylated and yielded the 4'-(N-methylpyridinium)-2,2':6',2''-terpyridine
      cations, including the 2-position pyridyl group which is difficult to be N
      alkylated due to the steric problem. Partial divalent copper atoms were reduced
      to cuprous ones in the solvothermal reactions, which made the mixed-valence
      copper atoms coexist in each compound. The mixed-valence complexes have a varied
      dimensionality (from 2D to 0D) and the Cu(I)Br cluster, which can be controlled
      by changing the metal-ligand ratio. Theoretical studies show that the
      nucleophilic attack of the nitrogen atom in the pendant pyridyl is more facile
      than others of terpyridine. A possible mechanism was also proposed.

PMID- 22391584
TI  - Long-term follow-up of prostate cancer patients treated with vaccine and
      definitive radiation therapy.
AB  - BACKGROUND: Vaccine therapy in combination with radiation therapy may improve
      distant and/or local control in prostate cancer. We present long-term follow-up
      data on the secondary and exploratory endpoints of safety and biochemical
      failure, respectively, from patients with clinically localized prostate cancer
      treated definitively with a poxviral vector-based therapeutic vaccine combined
      with external beam radiation therapy (EBRT). METHODS: Thirty-six prostate cancer
      patients received definitive EBRT plus vaccine. A total of 18 patients were
      treated with adjuvant standard-dose interleukin-2 (S-IL-2) (4 MIU m(-2)) and 18
      were treated with very low-dose IL-2 (M-IL-2) (0.6 MIU m(-2)). Seven patients
      were treated with EBRT alone. Twenty-six patients treated with EBRT plus vaccine
      returned for follow-up, and we reviewed the most recent labs and clinical notes
      of the remaining patients. RESULTS: Median follow-up for the S-IL-2, M-IL-2 and
      EBRT-alone groups was 98, 76 and 79 months, respectively. Actuarial 5-year PSA
      failure-free probability was 78%, 82% and 86% (P=0.58 overall), respectively.
      There were no significant differences between the actuarial overall survival and
      the prostate cancer-specific survival between the two vaccine arms. Of the 26
      patients who returned for follow-up, Radiation Therapy Oncology Group grade >=2
      genitourinary (GU) and gastrointestinal (GI) toxicity was seen in 19% and 8%,
      respectively, with no difference between the arms (P=1.00 and P=0.48 for grade
      >=2 GU and GI toxicity, respectively). In all, 12 patients were evaluated for PSA
      specific immune responses, and 1 demonstrated a response 66 months post
      enrollment. CONCLUSIONS: We demonstrate that vaccine combined with EBRT does not
      appear to have significant differences with regard to PSA control or late-term
      toxicity compared with standard treatment. We also found limited evidence of long
      term immune response following vaccine therapy.

PMID- 22391586
TI  - Harvesting microalgal biomass using submerged microfiltration membranes.
AB  - This study was performed to investigate the applicability of submerged
      microfiltration as a first step of up-concentration for harvesting both a
      freshwater green algae species Chlorella vulgaris and a marine diatom
      Phaeodactylum tricornutum using three lab-made membranes with different porosity.
      The filtration performance was assessed by conducting the improved flux step
      method (IFM) and batch up-concentration filtrations. The fouling autopsy of the
      membranes was performed by scanning electron microscopy (SEM), energy-dispersive
      X-ray spectroscopy (EDX) and Fourier transform infrared spectroscopy (FTIR). The
      cost analysis was estimated based on the data of a related full-scale submerged
      membrane bioreactor (MBR). Overall results suggest that submerged microfiltration
      for algal harvesting is economically feasible. The IFM results indicate a low
      degree of fouling, comparable to the one obtained for a submerged MBR. By
      combining the submerged microfiltration with centrifugation to reach a final
      concentration of 22% w/v, the energy consumption to dewater C. vulgaris and P.
      tricornutum is 0.84 kW h/m(3) and 0.91 kW h/m(3), respectively.

PMID- 22391587
TI  - Tostadin, a novel antibacterial peptide from an antagonistic microorganism
      Brevibacillus brevis XDH.
AB  - A novel small antibacterial peptide was obtained from the liquid culture of
      Brevibacillus brevis XDH, which is a broad-spectrum antagonistic bacterium
      isolated from the soil of Mountain Tai, China. This peptide was purified from the
      fermentation medium of strain XDH via ammonium sulfate precipitation, cation
      exchange chromatography, and reversed-phase high-performance liquid
      chromatography (HPLC), successively. The structure of the active linear peptide
      was elucidated using mass spectra (MS) and nuclear magnetic resonance (NMR)
      analyses that consisted of nine amino acids. This peptide was easily soluble in
      water, thermally stable and strongly inhibited the growth of Escherichia coli and
      Staphylococcus aureus in vitro. The present data support the identification of a
      novel antibacterial peptide, which was named Tostadin.

PMID- 22391588
TI  - Mass balance of pilot-scale pretreatment of sugarcane bagasse by steam explosion
      followed by alkaline delignification.
AB  - Five pilot-scale steam explosion pretreatments of sugarcane bagasse followed by
      alkaline delignification were explored. The solubilised lignin was precipitated
      with 98% sulphuric acid. Most of the pentosan (82.6%), and the acetyl group
      fractions were solubilised during pretreatment, while 90.2% of cellulose and
      87.0% lignin were recovered in the solid fraction. Approximately 91% of the
      lignin and 72.5% of the pentosans contained in the steam-exploded solids were
      solubilised by delignification, resulting in a pulp with almost 90% of cellulose.
      The acidification of the black liquors allowed recovery of 48.3% of the lignin
      contained in the raw material. Around 14% of lignin, 22% of cellulose and 26% of
      pentosans were lost during the process. In order to increase material recovery,
      major changes, such as introduction of efficient condensers and the reduction in
      the number of washing steps, should be done in the process setup.

PMID- 22391589
TI  - Thermochemical pre- and biological co-treatments to improve hydrolysis and
      methane production from poultry litter.
AB  - The biochemical methane potential (BMP) of raw poultry litter waste was assessed
      in batch assays. Biological co-treatment with Clostridium cellulolyticum,
      Caldicellulosiruptor saccharolyticum and Clostridium thermocellum as
      bioaugmentation strains, and thermochemical pre-treatments with lime and sodium
      hydroxide performed at different temperatures and pressures were applied as
      strategies to improve the BMP by favouring the hydrolysis of the cellulolytic
      material in the waste. Anaerobic digestion of the raw waste allowed a specific
      methane production of 145 +/- 14 LCH(4)kg(-1)VS, with 1% total solids and 0.72 g
      VS(inoculum)g(-1)VS(waste). The pre- and co-treatments contributed to a
      significant increase (up to 74%) in the waste solubilisation when using C.
      saccharolyticum, but methane production did not improve considerably. Therefore,
      the conversion of soluble organic matter to methane was the limiting step of the
      anaerobic digestion process of poultry litter waste.

PMID- 22391590
TI  - Activated carbon and biochar amendments decrease pore-water concentrations of
      polycyclic aromatic hydrocarbons (PAHs) in sewage sludge.
AB  - The aim of the research was to determine the influence of biochar and activated
      carbon (AC) on the freely dissolved concentration of polycyclic aromatic
      hydrocarbons (PAHs) in sewage sludge. Two different biochars (MSB and PMW) and
      two ACs (CP1 and BP2) were used in the present experiment. Addition of AC/biochar
      to sewage sludge caused significant decrease of freely dissolved PAHs
      concentration. Depending on the dose, the reduction of freely dissolved PAHs
      ranged from 56% to 95% (ACs) and from 0% to 57% (biochars). Only for the biochars
      was there a significant difference between short 7-d and long 30/60-d mixing
      time. It is concluded that both AC and biochar are effective at reducing PAH pore
      water concentrations, the more expensive and non-carbon negative AC having the
      greatest effect.

PMID- 22391591
TI  - Enantioselective oxidation of racemic secondary alcohols catalyzed by chiral
      Mn(III)-salen complexes with N-bromosuccinimide as a powerful oxidant.
AB  - We demonstrate an efficient enantioselective oxidation of secondary alcohols
      catalyzed by Mn(III)-salen complex using N-bromosuccinimide (NBS) as the oxidant.
      The new protocol is very efficient for the oxidative kinetic resolution of a
      variety of secondary alcohols, including ortho-substituted benzylic alcohols.

PMID- 22391592
TI  - Letter to the Editor: Regarding: Kraft S, Mackler E, Schlickman P, Welch K,
      DePestel DD (2011) Outcomes of therapy: vancomycin-resistant enterococcal
      bacteremia in hematology and bone marrow transplant patients. Supp Care Cancer
      19;1969-1974.

PMID- 22391593
TI  - Re: In response to "Clinical features and management of carboplatin-related
      hypersensitivity reactions in pediatric low grade glioma".

PMID- 22391594
TI  - Caring for a loved one with a malignant fungating wound.
AB  - PURPOSE: Caring for a loved one with a malignant fungating wound is very
      challenging and causes extreme physical and psychological distress. The aim of
      this study was to explore the experiences of carers who care for a loved one with
      a fungating breast wound. METHOD: To explore the lived experiences of carers, a
      methodological framework using Heideggerian hermeneutic phenomenology and semi
      structured interviews was used. Seven carers were interviewed from January until
      November 2009. RESULTS: Having to deal with a situation of a loved one with a
      visible cancer was hard for all the carers. The visibility of the cancer was one
      of the most shocking aspects to deal with from the perspective of the patient and
      the carer. The presence of the visible wound and a cancer at an advanced stage
      contributed to a change in the relationship and extreme suffering for both the
      patient and the carer. Despite many problems such as wound odour and copious
      discharge from the wound, which was difficult to control, carers did their best
      to help their loved one with the wound. Gradually, the wound became the centre of
      the patient and carer's life, and a great deal of time was spent trying to
      control the wound symptoms. All carers managed the wound on their own without
      help and advice from health care practitioners. For all of them, it was a major
      burden and they felt isolated. CONCLUSION: This study contributes to an
      understanding that the care of women and their carers needs strategies that are
      integrated in palliative wound care that takes a holistic and empathic approach
      that responds to patients' and carers' psychosocial and emotional needs and a
      practical need for information to help carers assist in managing the wound
      related symptoms.

PMID- 22391596
TI  - Convergent synthesis of the potent P2Y receptor antagonist MG 50-3-1 based on a
      regioselective Ullmann coupling reaction.
AB  - MG 50-3-1 (3, trisodium 1-amino-4-{4-[4-chloro-6-(2-sulfophenylamino)-1,3,5
      triazin-2-ylamino]-2-sulfophenylamino}-9,10-dioxo-9,10-dihydroanthracene 2
      sulfonate) is the most potent and selective antagonist (IC50 4.6 nM) for "P2Y1
      like" nucleotide-activated membrane receptors in guinea-pig taenia coli
      responsible for smooth muscle relaxation. Full characterization of the compound,
      however, e.g., at the human P2Y1 receptor, which is a novel potential target for
      antithrombotic drugs, as well as other P2 receptor subtypes, has been hampered
      due to difficulties in synthesizing the compound in sufficient quantity. MG 50-3
      1 would be highly useful as a biological tool for detailed investigation of
      signal transduction in the gut. We have now developed a convenient, fast, mild,
      and efficient convergent synthesis of 3 based on retrosynthetic analysis. A new,
      regioselective Ullmann coupling reaction under microwave irradiation was
      successfully developed to obtain 1-amino-4-(4-amino-2-sulfophenylamino)-9,10
      dioxo-9,10-dihydro-anthracene 2-sulfonate (8). Four different copper catalysts
      (Cu, CuCl, CuCl2, and CuSO4) were investigated at different pH values of sodium
      phosphate buffer, and in water in the absence or presence of base. Results showed
      that CuSO4 in water in the presence of triethylamine provided the best conditions
      for the regioselective Ullmann coupling reaction yielding the key intermediate
      compound 8. A new synthon (sodium 2-(4,6-dichloro-1,3,5-triazin-2
      ylamino)benzenesulfonate, 13) which can easily be obtained on a gram scale was
      prepared, and 13 was successfully coupled with 8 yielding the target compound 3.

PMID- 22391595
TI  - Enhancing patient-reported outcome measurement in research and practice of
      palliative and end-of-life care.
AB  - PURPOSE: Patient-reported outcome measurement (PROM) plays an increasing role in
      palliative and end-of-life (EOL) care but their use in EOL care and research
      remains varied and inconsistent. We aimed to facilitate pan-European
      collaboration to improve PROMs in palliative and EOL care and research. METHODS:
      The study includes a workshop with experts experienced in using PROMs in clinical
      care and research from Europe, North America, and Africa. Information from
      presentations, and plenary and group discussions was analysed using content
      analysis for extracting the main themes. RESULTS: Thirty-two professionals from
      15 countries and eight different professional backgrounds participated in the
      workshop. The discussion identified: 1) the need for standardisation with
      improvement of existing PROMs, e.g., with a modular system and an optional item
      pool; 2) the aspects of further development with a multi-professional approach
      taking into account cultural sensitivity especially for translated versions; and
      3) the need for guidance, training, and resources. An international network for
      sharing concepts, experiences, and solutions could enhance these steps of further
      development. CONCLUSION: PROMs must be based on rigorous scientific methods and
      respond to patient complexity. Coordinated pan-European collaboration including
      researchers and clinicians is required to develop and attain quality care and
      systematic research in outcome measurement in palliative and EOL care.

PMID- 22391597
TI  - Oxidation of 2-hydroxynevirapine, a phenolic metabolite of the anti-HIV drug
      nevirapine: evidence for an unusual pyridine ring contraction.
AB  - Nevirapine (NVP) is an anti-HIV drug associated with severe hepatotoxicity and
      skin rashes, which raises concerns about its chronic administration. There is
      increasing evidence that metabolic activation to reactive electrophiles capable
      of reacting with bionucleophiles is likely to be involved in the initiation of
      these toxic responses. Phase I NVP metabolism involves oxidation of the 4-methyl
      substituent and the formation of phenolic derivatives that are conceivably
      capable of undergoing further metabolic oxidation to electrophilic quinoid
      species prone to react with bionucleophiles. The covalent adducts thus formed
      might be at the genesis of toxic responses. As part of a program aimed at
      evaluating the possible contribution of quinoid derivatives of Phase I phenolic
      NVP metabolites to the toxic responses elicited by the parent drug, we have
      investigated the oxidation of 2-hydroxy-NVP with dipotassium nitroso-disulfonate
      (Fremy's salt), mimicking the one-electron oxidation involved in enzyme-mediated
      metabolic oxidations. We report herein the isolation and full structural
      characterization of a 1H-pyrrole-2,5-dione derivative as a major product,
      stemming from an unusual pyridine ring contraction.

PMID- 22391598
TI  - Supercritical fluid extraction and ultra performance liquid chromatography of
      respiratory quinones for microbial community analysis in environmental and
      biological samples.
AB  - Microbial community structure plays a significant role in environmental
      assessment and animal health management. The development of a superior analytical
      strategy for the characterization of microbial community structure is an ongoing
      challenge. In this study, we developed an effective supercritical fluid
      extraction (SFE) and ultra performance liquid chromatography (UPLC) method for
      the analysis of bacterial respiratory quinones (RQ) in environmental and
      biological samples. RQ profile analysis is one of the most widely used culture
      independent tools for characterizing microbial community structure. A UPLC
      equipped with a photo diode array (PDA) detector was successfully applied to the
      simultaneous determination of ubiquinones (UQ) and menaquinones (MK) without
      tedious pretreatment. Supercritical carbon dioxide (scCO(2)) extraction with the
      solid-phase cartridge trap proved to be a more effective and rapid method for
      extracting respiratory quinones, compared to a conventional organic solvent
      extraction method. This methodology leads to a successful analytical procedure
      that involves a significant reduction in the complexity and sample preparation
      time. Application of the optimized methodology to characterize microbial
      communities based on the RQ profile was demonstrated for a variety of
      environmental samples (activated sludge, digested sludge, and compost) and
      biological samples (swine and Japanese quail feces).

PMID- 22391599
TI  - A microwave-assisted bismuth nitrate-catalyzed unique route toward 1,4
      dihydropyridines.
AB  - The classical Hantzsch reaction is one of the simplest and most economical
      methods for the synthesis of biologically important and pharmacologically useful
      1,4-dihydropyridine derivatives. Bismuth nitrate pentahydrate under microwave
      irradiation is proven to act as a very efficient catalyst for a one-pot, three
      component synthesis of 1,4-dihydropyridines in excellent yields from diverse
      amines/ammonium acetate, aldehydes and 1,3-dicarbonyl compounds within 1-3 min
      under solvent-free conditions. The present environmentally benign procedure for
      the synthesis of 1,4-dihydropyridines is suitable for library synthesis and it
      will find application in the synthesis of potent biologically active molecules.
      The excellent yield and extreme rapidity of the method is due to a concurrent
      effect of the catalyst and microwave irradiation.

PMID- 22391600
TI  - Rapid and sensitive LC-MS/MS method for the determination of metoprolol in Beagle
      dog plasma with a simple protein precipitation treatment and its pharmacokinetic
      applications.
AB  - A rapid LC-MS/MS method with good accuracy and sensitivity was developed and
      validated for the pharmacokinetics study of metoprolol (MP) in beagle dogs. The
      plasma samples were simply precipitated by methanol and then analyzed by LC
      MS/MS. An Ultimate XB-C18 column (150 * 2.1 mm ID, 5 MUm) was used for
      separation, with methanol-water containing 0.2% formic acid (65:35, v/v) as the
      mobile phase at a flow rate of 0.2 mL/min. Monitoring ions of MP and internal
      standard (hydroxypioglitazone) were m/z 268.1/115.6 and m/z 373.1/150.2,
      respectively. The linear range was 3.03-416.35 ng/mL with an average correlation
      coefficient of 0.9996, and the limit of quantification was 3.03 ng/mL. The intra-
      and inter-day precision was less than 15%. At low, middle and high
      concentrations, the recovery, the matrix effect and the accuracy was in the range
      of 76.06%-95.25%, 93.67%-104.19% and 95.20%-99.96% respectively. The method was
      applied for the pharmacokinetics study of MP tartrate tablets (50 mg). The AUC(0
      t), T(max) and C(max) were respectively 919.88 +/- 195.67 MUg/L.h, 0.96 +/- 0.33
      h, 349.12 +/- 78.04 ng/mL.

PMID- 22391601
TI  - Bioactive phenolic amides from Celtis africana.
AB  - Nine compounds have been isolated for the first time from Celtis africana, namely
      trans-N-coumaroyltyramine (1), trans-N-feruloyltyramine (2), trans-N
      caffeoyltyramine (3), lauric acid (4), oleic acid (5), palmitic acid (6), lupeol
      (7), beta-sitosterol (8) and oleanolic acid (9), respectively. Their structures
      have been elucidated by different spectroscopic techniques. The isolated
      compounds were screened for their antioxidant, anti-inflammatory and
      acetylcholinestrease enzyme inhibitory activities. Compounds 1-3 showed
      significant antioxidant and anti-inflammatory activities and weak to moderate
      acetylcholinestrease enzyme inhibition activity.

PMID- 22391602
TI  - Chemical and antimicrobial evaluation of supercritical and conventional Sideritis
      scardica Griseb., Lamiaceae extracts.
AB  - Sideritis scardica Griseb., Lamiaceae (ironwort, mountain tea), an endemic plant
      of the Balkan Peninsula, has been used in traditional medicine in the treatment
      of antimicrobial infections, gastrointestinal complaints, inflammation and
      rheumatic disorders. This study reports a comparison between conventional
      (hydrodistillation HD and solvent extraction SE) and alternative (supercritical
      carbon dioxide SC CO2) extraction methods regarding the qualitative and
      quantitative composition of the obtained extracts as analyzed by GC and GC-MS
      techniques and their anitimicrobial activity. Different types of extracts were
      tested, the essential oil EO obtained by HD, EO-CO2 and AO-CO2 obtained by SC CO2
      at different preasures 10 and 30 MPa, at 40  degrees C, respectively, and the
      fractions A, B, C and D obtained by successive solvent extraction (SE) A:
      ethanol, B: diethyl ether, C: ethyl acetate and D: n-butanol). While EO was
      characterized by the presence of the high percentage of oxygenated monoterpenes
      and sesquiterpenes (30.01 and 25.54%, respectively), the rest of the investigated
      samples were the most abundant in fatty acids and their esters and diterpenes
      (from 16.72 to 71.07% for fatty acids and their esters, and from 23.30 to 72.76%,
      for diterpenes). Microbial susceptibility tests revealed the strong to moderate
      activity of all investigated extracts against the tested microorganisms (MIC from
      40 to 2,560 MUg/mL). Although differences in the chemical compositions determined
      by GC and GC-MS analysis were established, the displayed antimicrobial activity
      was similar for the all investigated extracts.

PMID- 22391603
TI  - Antibacterial activity and anticancer activity of Rosmarinus officinalis L.
      essential oil compared to that of its main components.
AB  - In this study, Rosmarinus officinalis L. essential oil and three of its main
      components 1,8-cineole (27.23%), alpha-pinene (19.43%) and beta-pinene (6.71%)
      were evaluated for their in vitro antibacterial activities and toxicology
      properties. R. officinalis L. essential oil possessed similar antibacterial
      activities to alpha-pinene, and a little bit better than beta-pinene, while 1,8
      cineole possessed the lowest antibacterial activities. R. officinalis L.
      essential oil exhibited the strongest cytotoxicity towards three human cancer
      cells. Its inhibition concentration 50% (IC50) values on SK-OV-3, HO-8910 and Bel
      7402 were 0.0250/00, 0.0760/00 and 0.130/00 (v/v), respectively. The cytotoxicity
      of all the test samples on SK-OV-3 was significantly stronger than on HO-8910 and
      Bel-7402. In general, R. officinalis L. essential oil showed greater activity
      than its components in both antibacterial and anticancer test systems, and the
      activities were mostly related to their concentrations.

PMID- 22391604
TI  - A 21-year-old woman with multiple cancers and a new brain lesion.

PMID- 22391606
TI  - Selecting stroke patients for intra-arterial therapy.
AB  - There is a great need for new treatments for acute ischemic stroke that will
      achieve greater rates of arterial recanalization and increase the population of
      patients who may benefit. Of several approaches under investigation, intra
      arterial therapy (IAT) is the farthest along in clinical development, but
      experience has shown that the increased rates of recanalization achieved are not
      always translated to improved patient outcomes. Proper patient selection, allied
      to efficient strategies aiming at faster recanalization and reperfusion, may
      result in better clinical outcomes and more rational use of therapeutic
      resources. While high-tech multimodal imaging has the great promise of
      identifying hypoperfused but still viable brain tissue, a number of clues suggest
      that relatively low-tech approaches similar to those that were used to
      demonstrate the efficacy of systemic thrombolysis, and which have emphasized the
      key role of time and clinical factors such as age, glucose, stroke severity, and
      infarct on noncontrast CT scan, deserve greater study as an efficient way to
      optimize IAT. Eventually it will be a combination of predictors that will enable
      us to most precisely identify the best patients for IAT and any other new
      revascularization therapies.

PMID- 22391605
TI  - American Academy of Neurology policy on pharmaceutical and device industry
      support.
AB  - OBJECTIVE: To examine the American Academy of Neurology (AAN)'s prevention and
      limitation of conflicts of interest (COI) related to relationships with
      pharmaceutical and medical device manufacturers and other medically related
      commercial product and service companies (industry). METHODS: We reviewed the
      AAN's polices governing its interactions with industry, mechanisms for
      enforcement, and the recent findings of the board-appointed COI task force, in
      the context of the 2009 David Rothman and colleagues' article in JAMA, the
      Council of Medical Specialty Societies (CMSS) Code for Interactions with
      Companies (Code), efforts of the American Medical Association in this area, and
      increased public and Congressional scrutiny of physician/physician organizations'
      relationships with industry. RESULTS: The AAN's Policy on Conflicts of Interest
      provides 4 mechanisms for addressing COI: avoidance, separation, disclosure, and
      regulation. The AAN's Principles Governing Academy Relationships with External
      Sources of Support, including recent amendments proposed by the COI task force,
      regulate industry interaction with AAN programming, products, and leadership.
      With the Policy, Principles, and other methods of COI prevention, the AAN meets
      or exceeds all recommendations of the CMSS Code. CONCLUSIONS: With its adherence
      to the Principles since 2004, the AAN has been a leader among professional
      medical associations in appropriately managing COI related to interactions with
      industry. Recent amendments to the Principles maintain the AAN's position as a
      leader in a time of increased public scrutiny of physicians' and professional
      medical associations' relationships with industry. The AAN is responsive to the
      recommendations of the COI task force, and has adopted the CMSS Code.

PMID- 22391607
TI  - Reflections for October.

PMID- 22391608
TI  - Normative data for the Montreal Cognitive Assessment (MoCA) in a population-based
      sample.

PMID- 22391609
TI  - Pearls & oy-sters: functional MRI: a primer for neurology residents.

PMID- 22391610
TI  - French government warns public about drug misuse.

PMID- 22391611
TI  - Government's plans to avoid unnecessary libel claims don't go far enough, say
      critics.

PMID- 22391612
TI  - Primary screening for human papillomavirus compared with cytology screening for
      cervical cancer in European settings: cost effectiveness analysis based on a
      Dutch microsimulation model.
AB  - OBJECTIVES: To investigate, using a Dutch model, whether and under what variables
      framed for other European countries screening for human papillomavirus (HPV) is
      preferred over cytology screening for cervical cancer, and to calculate the
      preferred number of examinations over a woman's lifetime. DESIGN: Cost
      effectiveness analysis based on a Dutch simulation model. Base case analyses
      investigated the cost effectiveness of more than 1500 different screening
      policies using the microsimulation model. Subsequently, the policies were
      compared for five different scenarios that represent different possible scenarios
      (risk of cervical cancer, previous screening, quality associated test
      characteristics, costs of testing, and prevalence of HPV). SETTING: Various
      European countries. POPULATION: Unvaccinated women born between 1939 and 1992.
      MAIN OUTCOME MEASURES: Optimal screening strategy in terms of incremental cost
      effectiveness ratios (costs per quality adjusted life years gained) compared with
      different cost effectiveness thresholds, for two levels of sensitivity and costs
      of the HPV test. RESULTS: Primary HPV screening was the preferred primary test
      over the age of 30 in many considered scenarios. Primary cytology screening was
      preferred only in scenarios with low costs of cytology and in scenarios with a
      high prevalence of HPV in combination with high costs of HPV testing.
      CONCLUSIONS: Most European countries should consider switching from primary
      cytology to HPV screening for cervical cancer. HPV screening must, however, only
      be implemented in situations where screening is well controlled.

PMID- 22391613
TI  - The impact of frailty and delirium on mortality in older inpatients.
AB  - BACKGROUND: delirium and frailty are common among hospitalised older people but
      delirium is often missed and frailty considered difficult to measure in clinical
      practice. OBJECTIVE: to explore the relationship between delirium and frailty in
      older inpatients and determine their impact on survival. DESIGN AND SETTING: the
      prospective cohort study of 273 patients aged >=75 years. MEASURES: patients were
      screened for delirium at presentation and on alternate days throughout their
      hospital stay. Frailty status was measured by an index of accumulated deficits
      (FI), giving a potential score from 0 (no deficits) to 1.0 (all 33 deficits),
      with 0.25 used as the cut-off between 'fit' and 'frail'. RESULTS: delirium was
      detected in 102 patients (mean FI: 0.33) and excluded in 171 (mean FI: 0.18) (P <
      0.005); 111 patients were frail. Among patients with delirium, the median
      survival in fit patients was 359 days (95% CI: 118-600) compared with 88 days for
      those who were frail (95% CI: 5-171; P < 0.05). CONCLUSION: delirium was
      associated with higher levels of frailty: the identification of frail patients
      may help to target those at a greatest risk of delirium. Survival following
      delirium was poor with the combination of frailty and delirium conferring a
      particularly bleak prognosis.

PMID- 22391614
TI  - Interpreting and evaluating the CASP-19 quality of life measure in older people.
AB  - OBJECTIVE: to investigate how to interpret changes on the CASP-19 quality of life
      scale for older people, and whether it discriminates between, and is responsive
      to, relevant differences or changes in participants' circumstances. METHODS:
      analysis of data from the English Longitudinal Study of Ageing for those
      completing CASP-19 in both Wave 1 and Wave 2 (n = 6,482). Cross-sectional and
      longitudinal comparisons, using multiple linear regression, of CASP-19 scores
      with respect to eight anchor variables. RESULTS: cross-sectional comparisons
      found differences in mean CASP-19 scores at Wave 1 between categories of anchor
      variables varied from 1.9 for living alone to 8.0 for being able to walk &frac14;
      mile with difficulty. Longitudinal comparisons of changes in CASP-19 found that
      subjects that had moved between categories of the anchor variables over 28
      months, had changed their mean CASP-19 score by about 1 unit in the expected
      direction, compared with the unchanged category. These changes were statistically
      significant for six of the eight anchors. CONCLUSIONS: the cross-sectional
      comparisons help interpret differences and indicate CASP-19 has discriminatory
      power. The longitudinal changes show that CASP-19 is responsive to changes in
      most anchor variables that reflect some aspects of quality of life.

PMID- 22391615
TI  - Association between emergency department resources and diagnosis of intimate
      partner violence.
AB  - OBJECTIVE: There is little information about which intimate partner violence
      (IPV) policies and services assist in the identification of IPV in the emergency
      department (ED). The objective of this study was to examine the association
      between a variety of resources and documented IPV diagnoses. METHODS: Using
      billing data assembled from 21 Oregon EDs from 2001 to 2005, we identified
      patients who were assigned a discharge diagnosis of IPV. We then surveyed ED
      directors and nurse managers to gain information about IPV-related policies and
      services offered by participating hospitals. We combined billing data, survey
      results, and hospital-level variables. Multivariate analysis assessed the
      likelihood of receiving a diagnosis of IPV depending on the policies and services
      available. RESULTS: In 754 597 adult female ED visits, IPV was diagnosed 1929
      times. Mandatory IPV screening and victim advocates were the most commonly
      available IPV resources. The diagnosis of IPV was independently associated with
      the use of a standardized intervention checklist (odds ratio: 1.71; 95%
      confidence interval: 1.04-2.82). Public displays regarding IPV were negatively
      associated with IPV diagnosis (odds ratio 0.56; 95% confidence interval: 0.35
      0.88). CONCLUSION: IPV remains a rare documented diagnosis. Most common hospital
      level resources did not demonstrate an association with IPV diagnoses; however, a
      standardized intervention checklist may play a role in clinician's likelihood of
      diagnosing IPV.

PMID- 22391616
TI  - An approach to design long-term monitoring and evaluation frameworks in multi
      actor systems--a case in water management.
AB  - Learning-by-doing and adaptive management require careful monitoring and
      evaluation of the outcomes of environmental policies and programs under
      implementation. Selecting relevant indicators is difficult, especially when
      monitoring over a longer period of time. Further challenges arise when policies
      are developed as a collaborative effort among multiple actors. This paper
      discusses an approach to design frameworks for long-term monitoring and
      evaluation in multi-actor systems. It uses Dynamic Actor Network Analysis (DANA)
      as an actor-sensitive method to reconstruct program theories. This is combined
      with elements of assumption-based planning to identify critical assumptions and
      associated indicators to incorporate the dynamic aspects related to long-term
      monitoring. An application of this approach is described for a case of water
      management in the Netherlands. Here, mapping multiple perspectives and
      identifying critical assumptions helped to broaden the scope of monitoring in
      important ways. Identifying associated indicators and expectations on their
      development in response to policy implementation proved more difficult. From this
      case, it can be concluded that the approach is feasible, useful, but also
      demanding. However, with continuing trends of networked governance and adaptive
      management, additional efforts to reflect these trends in monitoring and
      evaluation, through this and similar approaches, are needed.

PMID- 22391617
TI  - Essential competencies for program evaluators in a diverse cultural context.
AB  - Essential evaluator competencies as identified by Stevahn, King, Ghere, and
      Minnema (2005) were studied in regard to how well they generalize to an Asian
      (Taiwan) context. A fuzzy Delphi survey with two iterations was used to collect
      data from 12 experts. While most competencies fit Taiwan, there were a number of
      unique ones. A complete set of results is provided along with the implications of
      the findings and what they might mean for evaluation in Taiwan particularly in
      relationship to the professionalization of evaluation.

PMID- 22391618
TI  - Associative memory or algorithmic search: a comparative study on learning
      strategies of bats and shrews.
AB  - Two common strategies for successful foraging are learning to associate specific
      sensory cues with patches of prey ("associative learning") and using set decision
      making rules to systematically scan for prey ("algorithmic search"). We
      investigated whether an animal's life history affects which of these two foraging
      strategies it is likely to use. Natterer's bats (Myotis nattereri) have slow life
      history traits and we predicted they would be more likely to use associative
      learning. Common shrews (Sorex araneus) have fast life-history traits and we
      predicted that they would rely more heavily on routine-based search. Apart from
      their marked differences in life-history traits, these two mammals are similar in
      body size, brain weight, habitat, and diet. We assessed foraging strategy,
      associative learning ability, and retention time with a four-arm maze; one arm
      contained a food reward and was marked with four sensory stimuli. Bats and shrews
      differed significantly in their foraging strategies. Most bats learned to
      associate the sensory stimuli with the reward and remembered this association
      over time. Most shrews searched the maze using consistent decision-making rules,
      but did not learn or remember the association. We discuss these results in terms
      of life-history traits and other key differences between these species. Our
      results suggest a link between an animal's life-history strategy and its use of
      associative learning.

PMID- 22391619
TI  - Further characterization of acro-renal-uterine-mandibular syndrome: report of a
      case and review of earlier reports.

PMID- 22391620
TI  - History and molecular characteristics of a patient with terminal deletion of 14q.
      Is this another syndrome with a striking phenotype?

PMID- 22391621
TI  - Prenatal detection of an inverted duplication deletion in the long arm of
      chromosome 1 in a fetus with increased nuchal translucency. Molecular cytogenetic
      analysis and review of the literature.

PMID- 22391622
TI  - Correspondence: Further studies on a kindred reported by Li 2009 as 'A new
      syndrome of ankyloglossia and ulnar ray defects in Newfoundland kindred'. From
      'new syndrome' through EEC to ulnar mammary syndrome.

PMID- 22391624
TI  - Pro-inflammatory action of Candida albicans DNA in zymosan-induced arthritis.
AB  - OBJECTIVE: This study was designed to examine the potential ability of Candida
      albicans DNA to influence joint inflammation in a mouse model of zymosan-induced
      arthritis (ZIA) relating to Toll-like receptor-9 (TLR9) expression and cytokine
      production in different compartments. METHODS: To induce ZIA, mice were injected
      in the ankle joint with 180 MUg zymosan. TLR9 expression in synovial extracts,
      peritoneal macrophages, splenocytes and popliteal lymph node cells was analyzed
      by flow cytometry. The levels of interferon (IFN)-gamma, interleukin (IL)-6 and
      IL-10 in synovial fluid and sera were measured by ELISA. The expression of TLR9
      in the joints was determined by immunohistochemistry. RESULTS: A single
      intraperitoneal injection of C. albicans DNA did not elevate TLR9 expression and
      cytokine levels in the joints. It increased TLR9 expression by peritoneal
      macrophages isolated from healthy and arthritic mice and elevated the IFN-gamma
      level in circulation. In-vitro stimulation with DNA enhanced IL-6, IFN-gamma and
      IL-10 production by different cells isolated from mice with ZIA. CONCLUSION:
      These results suggest that small quantities of C. albicans DNA can provoke a pro
      inflammatory systemic response rather than locally in the joint.

PMID- 22391623
TI  - Ovine synovial membrane-derived mesenchymal progenitor cells retain the phenotype
      of the original tissue that was exposed to in-vivo inflammation: evidence for a
      suppressed chondrogenic differentiation potential of the cells.
AB  - BACKGROUND: The purpose of this study was to characterize the effect of post
      surgery joint inflammation on the chondrogenic differentiation capacity of
      mesenchymal progenitor cells (MPCs) derived from the synovial membrane (SM).
      METHODS: Six Suffolk-cross sheep were subjected to experimental anterior cruciate
      ligament (ACL) core surgeries. After they were killed 2 weeks after surgery, the
      volume of synovial fluid in the knees was measured and SM was collected for mRNA
      extraction and cell isolation. Cells were propagated and used for lineage
      specific differentiation assays using cell pellet cultures and mRNA extraction.
      Chondrogenic differentiation assays in the presence of exogenous interleukin
      1beta (IL-1beta) were also performed. RESULTS: The volume of synovial fluid from
      the operated knees was significantly greater than from the contralateral knees.
      Quantitative RT-PCR revealed that mRNA levels for IL-1beta and matrix
      metalloproteinases-3 and -13 in SM from the operated knees were significantly
      higher than those from the contralateral knees. The size of MPC pellets from
      operated knees (opMPC) cultured in chondrogenic medium were significantly smaller
      than the corresponding pellets generated with MPCs from contralateral knees
      (conMPC). Addition of 1-100 ng/ml IL-1beta significantly suppressed the resultant
      size of chondrogenic cell pellets from normal ovine SM-MPC. DISCUSSION: From
      these results, we conclude that cells from SM exposed to post-surgical
      inflammation are compromised by the inflammatory environment and that IL-1beta
      can inhibit the latent chondrogenic potential of normal MPCs. This suggests that
      if MPCs from injured joints do contribute to cartilage repair, their endogenous
      repair potential may become compromised by such post-injury joint inflammation.

PMID- 22391625
TI  - Genetic skin diseases predisposing to basal cell carcinoma.
AB  - Basal cell carcinoma (BCC) is the commonest cancer in humans. Predisposing
      factors reflect common genetic variations and environmental influences in most
      cases. However, an underlying Mendelian disorder should be suspected in a
      specific subset of patients, namely those with multiple, early onset lesions.
      Some specific conditions, including Gorlin, Bazex-Dupre-Christol and Rombo
      syndromes, and Xeroderma Pigmentosum, show BCC as a prominent feature. In
      addition, BCC may represent a relatively common, although less specific, finding
      in many other genodermatoses. These include disorders of DNA replication/repair
      functions (Bloom, Werner, Rothmund-Thomson and Muir-Torre syndromes),
      genodermatoses affecting the folliculo-sebaceus unit (Brooke-Spiegler, Schopf
      Schulz-Passarge and Cowden syndromes), immune response (cartilage-hair hypoplasia
      and epidermodysplasia verruciformis) and melanin biosynthesis (oculocutaneous
      albinism and Hermansky-Pudlak syndrome), and some epidermal nevus syndromes.
      Further conditions occasionally associated with BCCs exist, but the significance
      of the association remains to be proven.

PMID- 22391626
TI  - Observation of neighboring ortho-hydroxyl group participation in organocatalytic
      asymmetric sequential Michael-lactonization reactions: synthesis of highly
      substituted chiral spirodihydrocoumarins.
AB  - A general approach to asymmetric synthesis of highly substituted
      spirodihydrocoumarins with a quaternary stereocenter was achieved through
      neighboring ortho-hydroxyl group induced sequential Michael-lactonization
      reactions on 2-(2-nitrovinyl)phenols with alkyl cyclopentanone-2-carboxylates in
      the presence of a catalytic amount of quinine-NH-thiourea followed by p-TSA.

PMID- 22391628
TI  - Sounding the alarm for patients with obstructive sleep apnea.

PMID- 22391627
TI  - Evaluation of the prognostic value of TGF-beta superfamily type I receptor and
      TGF-beta type II receptor expression in nasopharyngeal carcinoma using high
      throughput tissue microarrays.
AB  - Gene expression profiling had revealed that TGF-beta superfamily type I receptor
      (also known as activin receptor-like kinase-1, ALK1) and TGFbetaR2 (TGF-beta type
      II receptor) were down-regulated in nasopharyngeal carcinoma (NPC) (P < 0.05,
      respectively). However, no study with significantly large clinical samples to
      address the relevance of ALK1 and TGFbetaR2 in NPC progression or in patient
      outcomes has been reported. This study aims to assess the possible correlations
      of ALK1 and TGFbetaR2 expression with NPC progression and their potential
      prognostic predictive ability in NPC outcomes. ALK1 and TGFbetaR2 mRNA and
      protein levels were detected by qRT-PCR and NPC tissue microarray (TMA), which
      included 742 tissue cores. Both mRNA and protein levels of ALK1 and TGFbetaR2
      were significantly lower in the cancer tissues compared with the non-cancerous
      tissues (P < 0.05). Epstein-Barr virus small RNA (EBER-1) hybridization signals
      in NPC showed significant associations with ALK1 and TGFbetaR2 proteins (P =
      0.000 and 0.003, respectively). In the final logistic regression analysis model,
      the abnormal expression of ALK1 and TGFbetaR2 were found to be independent
      contributors to nasopharyngeal carcinogenesis (P = 0.000 and 0.000,
      respectively). A survival analysis revealed that ALK1 (Disease Free Survival
      (DFS): P = 0.002, Overall Survival (OS): P = 0.007) and TGFbetaR2 (DFS: P =
      0.072, OS: P = 0.045) could predict the prognosis of NPC patients. The positive
      expression of ALK1 and TGFbetaR2 were independent risk factors for DFS and OS in
      multivariate analyses (DFS: P = 0.001 and 0.420, respectively; OS: P = 0.018 and
      0.047, respectively). These results suggest that ALK1 and TGFbetaR2 may be useful
      prognostic biomarkers in NPC.

PMID- 22391630
TI  - Differential effects of cholesterol and budesonide on biophysical properties of
      clinical surfactant.
AB  - INTRODUCTION: Corticosteroids have been widely used in clinical medicine as a
      first-line therapy to modify the inflammatory response in many pulmonary and
      systemic diseases. Inhaled and intratracheally administered corticosteroids have
      a particular interest in that their use allows the clinician to circumvent
      systemic steroid side effects. However, it is vital that corticosteroids
      delivered via the lungs not interfere with surface activity of the pulmonary
      surfactant lining layer. RESULTS: We found differential effects of cholesterol
      and budesonide on the biophysical properties of a cholesterol-free clinical
      surfactant preparation, Curosurf. At a low concentration up to 1%, both steroids
      play a similar role of fluidizing the surfactant film. However, when steroid
      concentration is increased to 10%, cholesterol induces a unique phase transition
      that abolishes the surface activity of the Curosurf film. By contrast, 10%
      budesonide simply fluidizes the film, thus having only limited effects on surface
      activity. DISCUSSION: Together with those of a previous study using a cholesterol
      containing surfactant, our findings suggest that cholesterol-free surfactant
      preparations may be more advantageous than cholesterol-containing preparations as
      a carrier of budesonide because a larger amount of the drug may be delivered to
      the lungs without significantly compromising the surface activity of pulmonary
      surfactant. METHODS: Langmuir balance was used to study the effect of cholesterol
      and budesonide added at different concentrations on surface activity of Curosurf.
      Atomic force microscopy (AFM) was used to reveal their effects on the interfacial
      molecular organization and lateral structure of Curosurf films.

PMID- 22391631
TI  - Enteral leucine supplementation increases protein synthesis in skeletal and
      cardiac muscles and visceral tissues of neonatal pigs through mTORC1-dependent
      pathways.
AB  - INTRODUCTION: Leucine (Leu) activates mammalian target of rapamycin (mTOR) to
      upregulate protein synthesis (PS). RESULTS: PS in skeletal muscles, heart, liver,
      pancreas, and jejunum, but not kidney, were greater in low protein supplemented
      with Leu (LP+L) than LP, but lower than high protein (HP). In longissimus dorsi
      muscle, protein kinase B phosphorylation was similar in LP and LP+L, but lower
      than HP. Although less than HP, p70 ribosomal S6 kinase 1 (S6K1) and eukaryotic
      initiation factor (eIF) 4E binding protein 1 (4EBP1) association with regulatory
      associated protein of mammalian target of rapamycin was greater in LP+L than LP,
      resulting in higher S6K1 and 4EBP1 phosphorylation. Feeding LP+L vs. LP decreased
      4EBP1.eIF4E and increased eIF4E.eIF4G formation, but not to HP. Similar results
      were obtained for S6K1 and 4EBP1 phosphorylation in gastrocnemius, masseter,
      heart, liver, pancreas, and jejunum, but not kidney. eIF2alpha and elongation
      factor 2 phosphorylation was unaffected by treatment. DICUSSION: Our results
      suggest that enteral Leu supplementation of a low protein diet enhances PS in
      most tissues through mTOR complex 1 pathways. METHODS: To examine enteral Leu
      effects on PS and signaling activation, 5-d-old piglets were fed for 24 h diets
      containing: (i) LP, (ii) LP+L, or (iii) HP.

PMID- 22391632
TI  - Multidose optimization simulation of erythropoietin treatment in preterm infants.
AB  - INTRODUCTION: Preterm infants commonly develop anemia requiring red blood cell
      transfusions (RBCTx). Although an alternative therapy is recombinant human
      erythropoietin (Epo), it is not widely employed. To provide a rigorous scientific
      basis supporting the latter approach, a model-based simulation analysis of
      endogenous erythropoiesis was developed. RESULTS: The
      pharmacodynamic/pharmacokinetic (PK/PD) model identified an optimal Epo dosing
      algorithm in preterm infants that demonstrated maximal efficacy when Epo was
      dosed frequently during the early weeks of life (when phlebotomy loss is
      greatest). Model-based simulations employing optimized Epo dosing predicted that
      13 of the 27 (46%) infants would avoid RBCTx ("good responders"). Importantly,
      simulation results identified five subject-specific covariate factors predictive
      of good Epo response. DISCUSSION: This simulation study provides a basis for
      possibly eliminating RBCTx in infants who can be selected for optimized Epo
      therapy. METHODS: Epo PD hemoglobin production parameters were determined in 27
      preterm infants studied intensively during the first 28 d of life. Model-derived
      Epo PD parameters were combined with PK parameters derived from the literature to
      simulate an optimized intravenous Epo bolus dosing schedule. The goal of this
      simulated optimized schedule was to eliminate RBCTx, as prescribed per current
      guidelines, in as many preterm infants as possible.

PMID- 22391633
TI  - The perinatal transition of the circulating metabolome in a nonhuman primate.
AB  - INTRODUCTION: The fetal-to-neonatal transition is one of the most complex
      processes in biological existence; much is unknown about this transition on the
      molecular and biochemical level. Based on growing metabolomics literature, we
      hypothesize that metabolomic analysis will reveal the key biochemical
      intermediates that change during the birth transition. RESULTS: Using two
      dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC
      * GC-TOFMS), we identified 100 metabolites that changed during this transition.
      Of these 100 metabolites, 23 demonstrated significant change during the first 72
      h. Of note, four intermediates of the tricarboxylic acid (TCA) cycle were
      identified (alpha-ketoglutaric acid, fumaric acid, malic acid, and succinyl-CoA),
      demonstrating a consistent rate of rise during the study. This may signify the
      transition of the neonate from a hypoxic in utero environment to an oxygen-rich
      environment. Important signaling molecules were also identified, including myo
      inositol and glutamic acid. DISCUSSION: GC * GC-TOFMS was able to identify
      important metabolites associated with metabolism and signaling. These data can be
      used as a baseline for normal birth transition, which may aid in future perinatal
      research investigations. METHODS: Late-preterm Macaca nemestrina were delivered
      by hysterotomy, with plasma drawn from the cord blood and after birth at eight
      additional time points to 72 h of age.

PMID- 22391634
TI  - Limited predictive value of early changes in EEG spectral power for neural injury
      after asphyxia in preterm fetal sheep.
AB  - INTRODUCTION: This study examined whether spectral analysis of the
      electroencephalogram (EEG) can discriminate between mild and severe hypoxic
      ischemic injury in the immature brain. RESULTS: Total EEG power was profoundly
      suppressed after umbilical cord occlusion and recovered to baseline by 5 h after
      15-min of occlusion, in contrast with transient recovery in the 25-min (P <
      0.05). Power spectra were not different between groups in the first 3 h; alpha
      and beta power were significantly higher in the 15-min group from 4 h, and Delta
      and theta power from 5 h (P < 0.05). The 25-min group showed severe neuronal loss
      in hippocampal regions and basal ganglia at 3 days, in contrast with no/minimal
      injury in the 15-min group. DISCUSSION: EEG power after asphyxia did not
      discriminate between mild and severe injury in the first 3 h in preterm fetal
      sheep. Severe subcortical neural injury was associated with persistent loss of
      high-frequency activity. METHODS: Chronically instrumented fetal sheep at 0.7
      gestation (101-104 days; term is 147 days) received either 15-min (n = 13) or 25
      min (n = 13) of complete umbilical cord occlusion. The Delta (0-3.9 Hz), theta (4
      7.9 Hz), alpha (8-12.9 Hz), and beta (13-22 Hz) components of the EEG were
      determined by power spectral analysis. Brains were taken at 3 days for
      histopathology.

PMID- 22391635
TI  - Thalamic changes in a preterm sample with periventricular leukomalacia:
      correlation with white-matter integrity and cognitive outcome at school age.
AB  - INTRODUCTION: Thalamic abnormalities have been well documented in preterms with
      periventricular leukomalacia (PVL), although their contribution to long-term
      cognitive dysfunctions has not been thoroughly investigated. RESULTS: Significant
      differences between groups were observed for global thalamic volume.
      Neuropsychological assessments showed that preterms with PVL scored within the
      normal range, although significantly below controls in the full intelligence
      quotient and the specific cognitive domains of processing speed and working
      memory. Correlations of several thalamic regions with Working Memory Index and
      FIQ were found in the PVL group. Moreover, thalamic atrophy correlated with white
      matter (WM) damage indexes (fractional anisotropy and radial diffusivity)
      assessed by diffusion tensor imaging. DISCUSSION: The findings suggest that
      thalamic damage is a common correlate of WM microstructural alterations and might
      be involved in the cognitive deficits seen in premature infants with PVL at
      school age. METHODS: We analyzed the impact of PVL-associated thalamic injury on
      cognitive status at school age and its correlation with WM integrity as measured
      by magnetic resonance imaging techniques. Thalamic volume and shape of 21 preterm
      children with PVL were compared with those of 11 preterm children of similar
      gestational age and birth weight with no evidence of focal WM abnormality.

PMID- 22391636
TI  - Study of leptin levels and gene polymorphisms in patients with central precocious
      puberty.
AB  - INTRODUCTION: Three single-nucleotide polymorphisms (SNPs) in the leptin (LEP) or
      leptin receptor (LEPR) genes were assessed for their association with central
      precocious puberty (CPP). RESULTS: The control group with the A/G SNP at LEPR 223
      or A/G SNP at LEPR 109 exhibited significantly higher peak luteinizing hormone
      (LH) levels. The leptin level in the CPP group was significantly higher than that
      in the control group, but SNPs in either LEP or LEPR gene could not explain this
      observation. DISCUSSION: In conclusion, SNPs at LEPR 223 and LEPR 109 were
      significantly associated with higher levels of LH in girls without CPP, but none
      of the genotypes at these SNPs were significantly associated with CPP. METHODS:
      The SNP genotypes of LEP (polymorphism at promoter at nt-2548) and LEPR (223A/G,
      109A/G) of 219 healthy girls and 249 girls diagnosed with CPP were compared.
      Allele frequencies in SNPs were compared with anthropometric measures,
      circulating leptin, hormones (estradiol, follicle-stimulating hormone, and LH),
      and lipid concentrations for CPP risk.

PMID- 22391637
TI  - M-ficolin concentrations in cord blood are related to circulating phagocytes and
      to early-onset sepsis.
AB  - INTRODUCTION: The pattern-recognition molecule M-ficolin is synthesized by
      monocytes and neutrophils. M-ficolin activates the complement system in a manner
      similar to mannan-binding lectin (MBL), but little is known about its role in
      host defense. Neonates are highly vulnerable to bacterial sepsis, in particular,
      due to their decreased phagocytic function. RESULTS: M-ficolin cord blood
      concentration was positively correlated with the absolute phagocyte count (rho
      0.51, P < 0.001) and with immature/total neutrophil ratio (rho 0.34, P < 0.001).
      When comparing infants with sepsis and controls, a high M-ficolin cord blood
      concentration (>1,000 ng/ml) was associated with early-onset sepsis (EOS)
      (multivariate odds ratio 10.92, 95% confidence interval 2.21-54.02, P = 0.003).
      Experimental exposure of phagocytes isolated from adult donors to Escherichia
      coli resulted in a significant time- and dose-dependent release of M-ficolin.
      DISCUSSION: In conclusion, M-ficolin concentrations were related to circulating
      phagocytes and EOS. Our results indicate that bacterial sepsis can trigger M
      ficolin release by phagocytes. Future studies should investigate whether M
      ficolin may be used as a marker of neutrophil activation during invasive
      infections. METHODS: We investigated M-ficolin in 47 infants with culture
      positive sepsis during the first 30 days of life (13 with EOS and in 94 matched
      controls. M-ficolin was measured in cord blood using time-resolved
      immunofluorometric assay (TRIFMA). Multivariate logistic regression was
      performed.

PMID- 22391638
TI  - Skin conductance peaks could result from changes in vital parameters unrelated to
      pain.
AB  - INTRODUCTION: Pain is usually assessed by the interpretation of behavior, which
      can be subjective. Therefore, there is an ongoing search for more objective
      methods. Performance of skin conductance measurement as a pain assessment tool is
      variable, as some studies report low specificity and a low predictive value of
      the method. The aim of this pilot study was to test whether autoregulation of the
      skin temperature influences the skin conductance of pain-free infants. RESULTS:
      Skin conductance was highly correlated with skin temperature in all subjects.
      Moreover, a significant change in all other vital parameters was observed on
      comparing before- and after-peak data. DISCUSSION: These results indicate that
      sympathetic neural activity to maintain homeostasis (such as autoregulation of
      skin temperature) results in skin conductance peaks. Real-time evaluation of the
      sympathetic nervous system would be valuable for pain assessment. However, the
      technique should be better defined to increase both sensitivity and specificity
      for the measurement of pain before use in daily practice can be advocated.
      METHODS: We included 11 infants, median (interquartile range (IQR)) age of 34 (13
      76) d, who were admitted to the surgical high-care unit for monitoring after
      surgery. None was treated with opioids or sedatives, and observational pain
      scores were low.

PMID- 22391639
TI  - Disruption of intracardiac flow patterns in the newborn infant.
AB  - INTRODUCTION: Consistent patterns of rotational intracardiac flow have been
      demonstrated in the healthy adult human heart. Intracardiac rotational flow
      patterns are hypothesized to assist in the maintenance of kinetic energy of
      inflowing blood, augmenting cardiac function. Newborn cardiac function is known
      to be suboptimal secondary to decreased receptor number and sympathetic
      innervation, increased afterload, and increased reliance on atrial contraction to
      support ventricular filling. Patterns of intracardiac flow in the newborn have
      not previously been examined. RESULTS: Whereas 5 of the 13 infants studied showed
      significant evidence of rotational flow within the right atrium, 8 infants showed
      little or no rotational flow. Presence or absence of rotational flow was not
      related to gestational age, birth weight, postnatal age, atrial size, or image
      quality. Despite absence of intra-atrial rotational flow, atrioventricular valve
      flow into the left and right ventricles later in the cardiac cycle could be seen,
      suggesting that visualization techniques were adequate. DISCUSSION: While further
      study is required to assess its exact consequences on cardiac mechanics and
      energetics, disruption to intracardiac flow patterns could be another contributor
      to the multifactorial sequence that produces newborn circulatory failure.
      METHODS: We studied 13 newborn infants, using three-dimensional (3D) cardiac
      magnetic resonance phase-contrast imaging (spatial resolution 0.84 mm, temporal
      resolution 22.6 ms) performed without sedation/anesthesia.

PMID- 22391640
TI  - Infants born very preterm react to variations of the acoustic environment in
      their incubator from a minimum signal-to-noise ratio threshold of 5 to 10 dBA.
AB  - INTRODUCTION: Very early preterm infants (VPIs) are exposed to unpredictable
      noise in neonatal intensive care units. Their ability to perceive moderate
      acoustic environmental changes has not been fully investigated. RESULTS:
      Physiological values of the 598 isolated sound peaks (SPs) that were 5-10 and 10
      15 dB slow-response A (dBA) above background noise levels and that occurred
      during infants' sleep varied significantly, indicating that VPIs detect them.
      Exposure to 10-15 dBA SPs during active sleep significantly increased mean heart
      rate and decreased mean respiratory rate and mean systemic and cerebral oxygen
      saturations relative to baseline. DISCUSSION: VPIs are sensitive to changes in
      their nosocomial acoustic environment, with a minimal signal-to-noise ratio (SNR)
      threshold of 5-10 dBA. These acoustic changes can alter their well-being.
      METHODS: In this observational study, we evaluated their differential auditory
      sensitivity to sound-pressure level (SPL) increments below 70-75 dBA equivalent
      continuous level in their incubators. Environmental (SPL and audio recording),
      physiological, cerebral, and behavioral data were prospectively collected over 10
      h in 26 VPIs (GA 28 (26-31) wk). SPs emerging from background noise levels were
      identified and newborns' arousal states at the time of SPs were determined.
      Changes in parameters were compared over 5-s periods between baseline and the 40
      s following the SPs depending on their SNR thresholds above background noise.

PMID- 22391641
TI  - Androgen receptor is overexpressed in boys with severe hypospadias, and ZEB1
      regulates androgen receptor expression in human foreskin cells.
AB  - INTRODUCTION: ZEB1 is overexpressed in patients with severe hypospadias. We
      examined the interaction between ZEB1 and the androgen receptor (AR) in vitro and
      the expression of AR in boys with hypospadias. RESULTS: ZEB1 and AR colocalize to
      the nucleus. Estrogen upregulated ZEB1 and AR expression. Chromatin
      immunoprecipitation (ChIP) demonstrated that ZEB1 binds to an E-box sequence in
      the AR gene promoter. AR expression is higher in subjects with severe hypospadias
      than those with mild hypospadias and control subjects (P < 0.05). ZEB1 physically
      interacts with AR in human foreskin cells. DISCUSSION: AR is overexpressed in
      patients with severe hypospadias. Environmental estrogenic compounds may increase
      the risk of hypospadias by facilitating the interaction between ZEB1 and AR.
      METHODS: Hs68 cells, a fibroblast cell line derived from neonatal human foreskin,
      were exposed to 0, 10, and 100 nmol/l of estrogen, after which the cellular
      localization of ZEB1 and AR was assessed using immunocytochemistry. To determine
      if ZEB1 interacted with the AR gene, ChIP was performed using ZEB1 antibody and
      polymerase chain reaction (PCR) for AR. Second, AR expression was quantified
      using real-time PCR and western blot in normal subjects (n = 32), and subjects
      with mild (n = 16) and severe hypospadia (n = 16).

PMID- 22391643
TI  - Combined effects of two mild stresses (cold and hypergravity) on longevity,
      behavioral aging, and resistance to severe stresses in Drosophila melanogaster.
AB  - Mild stresses may have positive effects on aging, longevity and resistance to
      severe stresses at various ages in Drosophila melanogaster. However, no study has
      combined two mild stresses to know whether more positive effects would be
      observed than with each stress alone. Cold and hypergravity (HG) have positive
      effects on some traits, but negative ones can also be observed, particularly in
      females. This study combined in the same flies cold and HG exposure. When cold
      and HG had each positive or negative effects their combination had additive
      effects but, when only one of the pretreatments had some effect, the effect of
      their combination usually reflected this effect. Therefore, combining two mild
      stresses with positive effects on aging and longevity can be more efficient than
      each stress alone. However, if one of these mild stresses had negative effects
      and the other one positive effects, the net result of their combination could be
      the suppression of the positive effect of the second stress. On the whole, if the
      net result of the combination of two mild stresses would be negative, it would be
      preferable not to combine them.

PMID- 22391642
TI  - Risk of bronchopulmonary dysplasia by second-trimester maternal serum levels of
      alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol.
AB  - INTRODUCTION: Although maternal serum alpha-fetoprotein (AFP), human chorionic
      gonandotropin (hCG), and estriol play important roles in immunomodulation and
      immunoregulation during pregnancy, their relationship with the development of
      bronchopulmonary dysplasia (BPD) in young infants is unknown despite BPD being
      associated with pre- and postnatal inflammatory factors. RESULTS: We found that
      these serum biomarkers were associated with an increased risk of BPD. Risks were
      especially high when AFP and/or hCG levels were above the 95th percentile and/or
      when unconjugated estriol (uE3) levels were below the 5th percentile (relative
      risks (RRs) 3.1-6.7). Risks increased substantially when two or more biomarker
      risks were present (RRs 9.9-75.9). DISCUSSION: Data suggested that pregnancies
      that had a biomarker risk and yielded an offspring with BPD were more likely to
      have other factors present that suggested early intrauterine fetal adaptation to
      stress, including maternal hypertension and asymmetric growth restriction.
      METHODS: The objective of this population-based study was to examine whether
      second-trimester levels of AFP, hCG, and uE3 were associated with an increased
      risk of BPD.

PMID- 22391645
TI  - The incidence of 30-day adverse events after colonoscopy among outpatients in the
      Netherlands.
AB  - OBJECTIVES: Colonoscopy is the gold standard for visualization of the colon. It
      is generally accepted as a safe procedure and major adverse events occur at a low
      rate. However, few data are available on structured assessment of (minor) post
      procedural adverse events. METHODS: Consecutive outpatients undergoing
      colonoscopy were asked for permission to be called 30 days after their procedure.
      A standard telephone interview was developed to assess the occurrence of (i)
      major adverse events (hospital visit required), (ii) minor adverse events, and
      (iii) days missed from work. Adverse events were further categorized in definite
      , possible-, and unrelated adverse events. Patients were contacted between
      January 2010 and September 2010. RESULTS: Out of a total of 1,528 patients who
      underwent colonoscopy and gave permission for a telephone call, 1,144 patients
      were contacted (response: 75%), 49% were male, the mean age was 59 years (s.d.:
      14). Thirty-four patients (3%) reported major adverse events. These were definite
      related in nine (1%) patients, possible-related in 6 (1%), and unrelated in 19
      patients (2%). Minor adverse events were reported by 466 patients (41%). These
      were definite-related in 336 patients (29%), possible-related in 36 (3%), and
      unrelated in the remaining 94 patients (8%). Female gender (odds ratio (OR):
      1.5), age <50 years (OR: 1.5), colonoscopy for colorectal cancer
      screening/surveillance (OR: 1.6), and fellow-endoscopy (OR: 1.7) were risk
      factors for the occurrence of any definite-related adverse event. Patients who
      reported definite-related adverse events were significantly less often willing to
      return for colonoscopy (81 vs. 88%, P<0.01) and were less often positive about
      the entire colonoscopy experience (84 vs. 89%, P=0.04). CONCLUSIONS: Structured
      assessment of post-colonoscopy adverse events shows that these are more common
      than generally reported. Close to one-third of patients report definite-related
      adverse events, which are major in close to 1 in 100 patients. The occurrence of
      adverse events does have an impact on the willingness to return for colonoscopy.

PMID- 22391646
TI  - Laser-guided percutaneous kidney access with the Uro Dyna-CT: first experience of
      three-dimensional puncture planning with an ex vivo model.
AB  - BACKGROUND AND PURPOSE: Safe and successful puncture of the kidney's collecting
      system is essential for acute therapy of hydronephrosis or as part of
      percutaneous nephrolithotomy. The procedure is technically challenging and might
      lead to major complications. We describe the feasibility of a laser guidance
      system and three-dimensional puncture planning in the endourological operation
      room. MATERIALS AND METHODS: An Uro Dyna-CT of the biological model was performed
      with the Artis Zee((r)) Ceiling (Siemens Medical Solutions, Erlangen, Germany) to
      gain multiplanar reconstructions. 10 punctures were performed with the syngo
      iGuide((r)) laser guidance system. Puncture success was depicted with antegrade
      contrast filling of the collecting system and fluoroscopic control. Puncture
      time, tract length, and fluoroscopy time was documented. RESULTS: Data
      acquisition (8 s) and 3D rendering (48 s) was possible in approximately 1 min.
      Median time for planning the punctures was 7 [5-15] min. Median puncture time was
      4.6 [2-10.2] min. Median tract length was 4.96 [4.33-6.5] cm. Median fluoroscopy
      time was 0.4 [0.2-1] min. 9 of 10 punctures were successful. A second puncture
      was needed to gain access to the collecting system in one case, and one puncture
      was broken up. CONCLUSION: The tested laser guidance system was feasible to
      perform successful percutaneous punctures of the kidney in this ex vivo study.
      Handling was intuitive and time within acceptable limits. Due to the requirement
      of multiplanar reconstructions with higher radiation exposure to the patient than
      with standard fluoroscopy, this technique should be limited to complex cases.

PMID- 22391647
TI  - Microbial colonization and ureteral stent-associated storage lower urinary tract
      symptoms: the forgotten piece of the puzzle?
AB  - PURPOSE: Ureteral stents are frequently associated with side effects. Most
      patients suffer from storage lower urinary tract symptoms (LUTS). Storage LUTS
      are commonly attributed to the irritation of the trigone, smooth muscle spasm or
      a combination of factors. The relationship between microbial ureteral stent
      colonization (MUSC) and de novo or worsening storage LUTS has not been
      investigated yet. METHODS: Five hundred ninety-one polyurethane ureteral stents
      from 275 male and 153 female patients were prospectively evaluated. The removed
      stents were sonicated to dislodge adherent microorganisms. Urine flow cytometry
      was performed to detect pyuria. A standardized urinary symptom questionnaire was
      given to all patients. RESULTS: Thirty-five per cent of male and 28% of female
      cases showed de novo or worsened storage LUTS. MUSC was more common in patients
      with storage LUTS compared to patients without storage LUTS (men: 26 vs. 13%,
      respectively, P < 0.05; women: 63 vs. 48%, respectively, P = 0.13). Pyuria was
      significantly more common in patients with storage LUTS compared to patients
      without storage LUTS (men: 55 vs. 40%, respectively, P < 0.05; women: 70 vs. 45%,
      respectively, P < 0.05). No significant correlation was observed between the
      detected genera of microorganisms and storage LUTS. CONCLUSIONS: Our data show a
      significant association between MUSC- and stent-related de novo experienced or
      worsened storage LUTS in men. The incidence of MUSC is most common in both female
      and male patients with storage LUTS and accompanying pyuria. In these patients, a
      combination of antibiotics and anti-inflammatory drugs may be regarded as
      treatment option.

PMID- 22391649
TI  - Molecular aspects of prostate cancer.

PMID- 22391648
TI  - The association of cruciferous vegetables intake and risk of bladder cancer: a
      meta-analysis.
AB  - OBJECTIVE: This meta-analysis of cohort and case-control studies was undertaken
      to evaluate the relationship between cruciferous vegetables intake and risk of
      bladder cancer. METHODS: Eligible studies were retrieved via both computer
      searches and review of references. The summary relative risks (RRs) with 95%
      confidence interval (CI) for the highest versus the lowest intake of cruciferous
      vegetables were calculated. Heterogeneity and publication bias were also
      evaluated. RESULTS: Five cohort and five case-control studies were included. A
      significantly decreased risk with bladder cancer was observed in overall
      cruciferous vegetables intake group (RR = 0.80; 95% CI 0.69-0.92) and subgroup of
      case-control studies (RR = 0.78; 95% CI, 0.67-0.89), but not in cohort studies
      (RR = 0.86; 95% CI, 0.61-1.11). No heterogeneity and publication bias were
      detected across studies. CONCLUSION: Our findings support that cruciferous
      vegetables intake was related to the decreased risk of bladder cancer. Because of
      the limited number of studies, further well-designed prospective studies are
      needed to explore the protective effect of cruciferous vegetables on bladder
      cancer.

PMID- 22391650
TI  - Sevoflurane-induced delayed neuroprotection involves mitoK(ATP) channel opening
      and PKC epsilon activation.
AB  - There is an increasing body of evidence that a brief exposure to anesthesia
      induces ischemic tolerance in rat brain (anesthetic preconditioning). However, it
      is unknown whether preconditioning with sevoflurane, a commonly used volatile
      anesthetic in current clinical practice, produces a delayed window of
      neuroprotection against ischemia and what the mechanisms are for this protection.
      To address these issues, adult male Sprague-Dawley rats were subjected to middle
      cerebral arterial occlusion (MCAO) for 2 h. Sevoflurane preconditioning was
      induced 24 h before brain ischemia by exposing the animals to sevoflurane at 1.0
      minimum alveolar concentration (2.4%) in oxygen for 60 min. Animals
      preconditioned with sevoflurane had lower neurological deficit scores and smaller
      brain infarct volumes than animals with brain ischemia at 6 and 24 h after MCAO,
      respectively. Application of a selective antagonist for mitochondrial ATP
      sensitive potassium (mitoK(ATP)) channel, 5-hydroxydecanoate (5-HD, 40 mg/kg
      i.p.) 30 min before sevoflurane exposure attenuated this beneficial effect.
      Moreover, protein kinase C epsilon (PKC epsilon) was translocated to the membrane
      fraction at 6 h, but not 24 h, after brain reperfusion in animals preconditioned
      with sevoflurane and this effect was also abolished by 5-HD. We concluded that
      sevoflurane preconditioning induces a delayed neuroprotection and that
      mitochondrial K(ATP) channels and PKC epsilon may be involved in this
      neuroprotection.

PMID- 22391651
TI  - Consistent isomiR expression patterns and 3' addition events in miRNA gene
      clusters and families implicate functional and evolutionary relationships.
AB  - 3' addition events in miRNAs are widely detected and may contribute to miRNA
      stability, but little is known about details of the events in miRNA gene clusters
      and families. Here, we performed a comprehensive analysis of isomiR expression
      patterns and 3' additions in miRNA gene clusters and families by analyzing high
      throughput sequencing dataset. According to dominant modified isomiRs, miRNA
      members in many miRNA gene clusters and families showed the same 3' additional
      non-template nucleotides. Although clustered miRNAs and homologous miRNAs had
      consistent or inconsistent expression levels, we found many of them showed
      consistent expression patterns at isomiR levels. These findings revealed similar
      processing mechanism and 3' modification event of miRNAs in gene clusters and
      families through miRNA maturation process. The consistent maturation mechanism
      may contribute to co-regulate biological processes, and may originate from
      ancestral miRNA genes through complex duplication history.

PMID- 22391652
TI  - cDNA cloning of heat shock protein 90 gene and protein expression pattern in
      response to heavy metal exposure and thermal stress in planarian Dugesia
      japonica.
AB  - Heat shock protein 90 (HSP90) is an abundant and highly conserved molecular
      chaperone, playing important roles in multiple cellular stress responses. The
      full-length cDNA of planarian Dugesia japonica Hsp90 (designated DjHsp90) was
      firstly cloned using rapid amplification of cDNA ends (RACE) techniques. It is
      2,354 bp, including an open reading frame (ORF) of 2,148 bp encoding a
      polypeptide of 715 amino acids with all five HSP90 family signatures. We
      sequenced the ORF sequences from genomic DNA, and found only one intron (48 bp)
      existed in Djhsp90 gene structure. We used western blot and immunohistochemistry
      to analyze the expression pattern of DjHsp90 in response to heavy metal exposure
      and thermal stress at the protein level. Our results show that low doses of heavy
      metals and elevated culture temperature induced, but high doses of heavy metals
      and severe heat shock inhibited DjHsp90 expression. In response to heavy metals
      and thermal stress, DjHsp90-positive cells only appeared in the parenchymal
      tissue under epidermis cells along the bilateral from head to tail. These
      positive cells are presumably sensor cells that can detect external environment
      changes. Our work provides basic data for the study of stress responses in
      planarians.

PMID- 22391653
TI  - Porcine SPP1 gene polymorphism association with phenotypic traits in the Landrace
      * Jeju (Korea) Black pig F2 population.
AB  - This study examined polymorphisms of the secreted phosphoprotein 1 (SPP1) gene
      and its association with growth and carcass traits in the F(2) population of the
      crossbred Landrace * Jeju (Korea) Black pig. The authors detected the
      presence/absence polymorphisms of short interspersed nuclear element in the SPP1
      intron 6 of the population; they then designated the longer fragment as allele A
      and the shorter one as allele B. The SPP1 A/B heterozygous pigs evidenced
      significantly heavier body weight at birth and on days 21 and 70, and a higher
      level of average daily gain during the early developmental period than was seen
      in the A/A and B/B homozygous pigs (P < 0.05). Further, the SPP1 A/B heterozygous
      pigs evidenced significantly greater body length, less backfat thickness measured
      at three different sites, and larger loin muscle area than the homozygotes (P <
      0.05). On the other hand, the levels of late average daily gain, 140th-day body
      weight, and marbling score were not significantly associated (P > 0.05). The
      results of this study reveal faster growth rate and differences in pig
      productivity according to genotypes of the SPP1 gene. These findings demonstrate
      that SPP1 genotypes may effectively function as molecular genetic markers for the
      improvement of Jeju Black pig-related crossbreeding systems.

PMID- 22391655
TI  - Is planning for change an oxymoron or a prescription for success? your role in
      advocacy, the IOM future of nursing report, and the importance of therapy in home
      care and hospice.

PMID- 22391654
TI  - Croatian national reference Y-STR haplotype database.
AB  - A reference Y-chromosome short tandem repeat (STR) haplotype database is needed
      for Y-STR match interpretation as well as for national and regional
      characterization of populations. The aim of this study was to create a
      comprehensive Y-STR haplotype database of the Croatian contemporary population
      and to analyze substructure between the five Croatian regions. We carried out a
      statistical analysis of the data from previously performed genetic analyses
      collected during routine forensic work by the Forensic Science Centre "Ivan
      Vucetic". A total of 1,100 unrelated men from eastern, western, northern,
      southern and central Croatia were selected for the purpose of this study. Y-STRs
      were typed using the AmpFISTR Yfiler PCR amplification kit. Analysis of molecular
      variance calculated with the Y chromosome haplotype reference database online
      analysis tool included 16 population samples with 20,247 haplotypes. A total of
      947 haplotypes were recorded, 848 of which were unique (89.5%). Haplotype
      diversity was 0.998, with the most frequent haplotype found in 9 of 1,100 men
      (0.82%). Locus diversity varied from 0.266 for DYS392 to 0.868 for DYS385.
      Discrimination capacity was 86.1%. Our results suggested high level of similarity
      among regional subpopulations within Croatia, except for mildly different
      southern Croatia. Relative resemblance was found with Bosnia and Herzegovina and
      Serbia. Whit Atheys' Haplogroup Predictor was used to estimate the frequencies of
      Y-chromosome haplogroups. I2a, R1a, E1b1b and R1b haplogroups were most frequent
      in all Croatian regions. These results are important in forensics and contribute
      to the population genetics and genetic background of the contemporary Croatian
      population.

PMID- 22391656
TI  - Views on the future of nursing and home healthcare: the future of nursing in home
      healthcare is now.
AB  - "My view you know is that the ultimate destination is the nursing of the sick in
      their own homes. ... I look to the abolition of all hospitals and workhouse
      infirmaries. But it is no use to talk about the year 2000." -Florence
      Nightingale, 1867 ().

PMID- 22391657
TI  - Views on the future of nursing and home healthcare: the future of nursing for
      home healthcare.
AB  - "The Future of Nursing: Leading Change, Advancing Health" from the Institute of
      Medicine () has created a long-overdue national discussion about nursing's role
      in the healthcare delivery system and what it will take for nurses to address
      these possibilities. For home healthcare nurses in particular, the next 10 years
      are going to result in drastic changes in practice and operations in home
      healthcare nursing practice. Most of these changes are going to be positive from
      the home healthcare nurse's perspective. However, I am concerned that home
      healthcare nurses are not ready for the extent of these drastic changes, and I
      present several scenarios that could occur, based on the IOM report and existing
      research.

PMID- 22391658
TI  - Hand hygiene practices of home visiting community nurses: perceptions,
      compliance, techniques, and contextual factors of practice using the World Health
      Organization's "five moments for hand hygiene".
AB  - In this observational study, the perceptions, compliance, techniques, and
      contextual issues of hand hygiene practices among community clinicians (nurses)
      during 103 hand hygiene opportunities (based on the World Health Organization
      "Five Moments for Hand Hygiene") in 40 patient care episodes were examined.
      Compliance with standard hand hygiene practices was generally poor, with many
      contextual influences making compliance difficult. Clinician preferences and
      convenience are important considerations in hand hygiene compliance. Improving
      home-visiting community clinicians' hand hygiene practices requires addressing
      contextual issues related to the availability of hand hygiene equipment, such as
      alcohol-based hand rubs, as well as hand hygiene in-service education to update
      knowledge on hand hygiene for everyday practice in community settings.

PMID- 22391662
TI  - The management of respiratory insufficiency in patients with ALS at or near the
      end of life.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease causing
      progressive paralysis and eventual death, usually from respiratory failure.
      Treatment for ALS is focused primarily on optimal symptom management because
      there is no known cure. Respiratory symptoms that occur are related to the
      disease process and can be very distressing for patients and their loved ones.
      Recommendations on the management of respiratory insufficiency are provided to
      help guide clinicians caring for patients with ALS.

PMID- 22391660
TI  - Adults with sickle cell disease: an interdisciplinary approach to home care and
      self-care management with a case study.
AB  - The complexity of caring for adults with sickle cell disease (SCD) strains the
      confines of a care-segregated medical system. As treatment protocols have
      dramatically improved since 1990, many patients with SCD are now living well
      beyond their 6th decade of life. This improved survival rate presents
      opportunities and challenges for the home healthcare nurse in the management of
      adult patients with SCD. The home healthcare nurse is essential in the
      coordination of interdisciplinary health team members to reduce pain episodes and
      the potentially catastrophic complications of renal failure, pulmonary disease,
      and cardiovascular events. In addition, the home healthcare nurse serves as
      patient advocate for the transition from acute care to home, as well as advocate
      for healthcare maintenance of vision, musculoskeletal involvement, and social and
      psychological support. This article seeks to provide a viable network for home
      healthcare nurses to establish self-care management and support of the adult
      patient with SCD.

PMID- 22391664
TI  - Reimbursement for therapy in medicare home health:  balancing patient needs and
      program integrity.

PMID- 22391665
TI  - Reflections of a hospice physical therapist: patient-centered care bringing
      quality toward end of life.
AB  - When discussing hospice care with physical therapy (PT) students, other
      healthcare professionals, patients, and families, they often ask: What do you do
      with a hospice patient? What goals can they actually achieve? What rehab
      potential do they actually have? My answer is: What does the patient want to be
      able to do? How does he or she want to improve his or her mobility? Hospice PT is
      all about the quality of the end of a patient's life.

PMID- 22391666
TI  - A community-wide quality improvement project on patient care transitions reduces
      30-day hospital readmissions from home health agencies.
AB  - Approximately 1 in 5 Medicare patients are rehospitalized within 30 days of
      discharge. The Harlingen Hospital Referral Region, an area defined by the
      Dartmouth Atlas as 35 ZIP codes in South Texas, reduced 30-day hospital
      readmission rates and associated costs through its participation in the Centers
      for Medicare & Medicaid Services Care Transitions project. The project emphasized
      a community-wide focus on 4 quality improvement areas: (a) the problem of
      rehospitalization, (b) improving cross-setting collaboration, (c) access to
      performance data, and (d) implementation of best practice interventions to reduce
      avoidable hospitalizations.

PMID- 22391667
TI  - Solvent and substituent effects on aggregation constants of perylene bisimide pi
      stacks--a linear free energy relationship analysis.
AB  - A series of six perylene bisimides (PBIs) with hydrophilic and hydrophobic side
      chains at the imide nitrogens were applied for a comparative study of the solvent
      and structural effects on the aggregation behaviour of this class of dyes. A
      comparison of the binding constants in tetrachloromethane at room temperature
      revealed the highest binding constant of about 10(5) M(-1) for a PBI bearing
      3,4,5-tridodecyloxyphenyl substituents at the imide nitrogens, followed by 3,4,5
      tridodecylphenyl and alkyl-substituted PBIs, whereas no aggregation could be
      observed in the accessible concentration range for PBIs equipped with bulky 2,6
      diisopropylphenyl substituents at the imide nitrogens. The aggregation behaviour
      of three properly soluble compounds was investigated in 17 different solvents
      covering a broad polarity range from nonpolar n-hexane to highly polar DMSO and
      water. Linear free energy relationships (LFER) revealed a biphasic behaviour
      between Gibbs free energies of aggregation and common empirical solvent polarity
      scales indicating particularly strong pi-pi stacking interactions in nonpolar
      aliphatic and polar alcoholic solvents whilst the weakest binding is observed in
      dichloromethane and chloroform. Accordingly, PBI aggregation is dominated by
      electrostatic interactions in nonpolar solvents and by solvophobic interactions
      in protic solvents. In water, the aggregation constant is increased far beyond
      LFER expectations pointing at a pronounced hydrophobic effect.

PMID- 22391669
TI  - Suspicion of duplicate publication regarding "J Anesth 2011; 25:953-4".

PMID- 22391668
TI  - Effect of wound infiltration with bupivacaine on postoperative analgesia in
      neonates and infants undergoing major abdominal surgery: a pilot randomized
      controlled trial.
AB  - PURPOSE: Postoperative pain management is essential in the perioperative care of
      neonates and infants but it requires a high level of care. Wound infiltration
      with bupivacaine, a long-acting local anesthetic, is a simple method with minimal
      complications. However, studies on the effectiveness of wound infiltration in
      neonates and infants are lacking. The purpose of this study was to investigate
      the effectiveness of wound infiltration with bupivacaine for postoperative
      analgesia in neonates and infants undergoing abdominal surgery. METHODS: A
      prospective, randomized controlled trial was conducted in 34 neonates and
      infants. The patients were randomized into two groups: the bupivacaine (B) group
      and the control (C) group. A standardized anesthetic protocol was used for each
      patient. Before wound closure, the surgical site of each patient in the B group
      was infiltrated with 2 mg/kg of bupivacaine, whereas no surgical site anesthetic
      infiltration was used in the C group. The neonatal infant pain scale (NIPS) score
      was used to evaluate postoperative pain, and fentanyl 0.5-1.5 MUg/kg was
      administered when the NIPS score was >=4. In regard to the fentanyl requirement,
      the NIPS score and the numbers of patients whose NIPS score was >=4 were compared
      between the two groups. RESULTS: The median fentanyl dose requirements in the B
      group and C group were 1 and 0.5 MUg/kg, respectively; and the difference was not
      statistically significant (p = 0.255). The postoperative NIPS scores in the two
      groups were not significantly different. In addition, there were no significant
      differences in the numbers of patients whose NIPS score was >=4 at 6, 12, 18, and
      24 h postoperatively. CONCLUSIONS: In neonates and infants, wound infiltration
      with bupivacaine had no significant effect on pain relief or fentanyl requirement
      during the first 24 h after major abdominal surgery.

PMID- 22391671
TI  - Parker Flex-Tip Tube(r) provides higher intubation success with the Pentax-AWS
      Airwayscope(r) despite the AWS tip being inserted into the vallecula.
AB  - The Parker Flex-Tip((r)) tube, in combination with the Pentax-Airwayscope((r))
      (AWS), is anecdotally reported to facilitate intubation when the AWS tip fails to
      be inserted behind the epiglottis. We examined whether the Parker tube
      facilitates intubation when the AWS tip is inserted into the vallecula. Forty
      patients were randomly assigned into either the standard or Parker tube group.
      Following general anesthesia induction, AWS intubation was attempted with the
      blade tip inserted into the vallecula. After obtaining an optimal laryngeal view,
      the tube was advanced toward the glottis. The laryngoscopist allowed additional
      adjustment of the blade tip direction when the first tube insertion failed
      because of involvement or folding of the epiglottis resulting from advancement of
      the tube. The primary outcome was defined as the success rate for intubation and
      secondary outcome as the time needed for tube placement. The Parker tube provided
      both a higher intubation success rate (17/20 vs. 4/20, P < 0.01), and a faster
      intubation time (17 +/- 5 s vs. 25 +/- 4 s, P < 0.01), than the standard tube. We
      conclude the use of the Parker tube in combination with the AWS is an optional
      technique allowing the laryngoscopist to obtain more reliable intubation success
      despite insertion of the AWS tip into the vallecula.

PMID- 22391670
TI  - Electrostimulation with or without ultrasound-guidance in interscalene brachial
      plexus block for shoulder surgery.
AB  - In a prospective controlled trial to compare conventional interscalene brachial
      plexus block (ISBPB) using anatomic landmarks and electro-stimulation with a
      combined technique of ultrasound guidance followed by nerve stimulation, 60
      patients were randomized into 2 matched equal groups: Group A using nerve
      stimulation (NS) alone and Group B using the combination of ultrasound and NS.
      The time to detect the plexus (3.9 +/- 4 min in Group A and 3.3 +/- 1.4 min in
      Group B) was not significantly different. We needed to reposition the needle once
      (n = 13) or twice (n = 4) in Group B. First-shot motor response was achieved in
      all but one patient in Group A; here we were only able to locate the plexus by
      use of ultrasound. None of the patients needed general anaesthesia. There were no
      significant differences between postoperative pain, motor power, or patient's
      satisfaction. ISBPB seems similarly effective using electro-stimulation and
      ultrasound if performed by experienced anesthesiologists.

PMID- 22391672
TI  - Let-7b is a novel regulator of hepatitis C virus replication.
AB  - The non-coding microRNA (miRNA) is involved in the regulation of hepatitis C
      virus (HCV) infection and offers an alternative target for developing anti-HCV
      agent. In this study, we aim to identify novel cellular miRNAs that directly
      target the HCV genome with anti-HCV therapeutic potential. Bioinformatic analyses
      were performed to unveil liver-abundant miRNAs with predicted target sequences on
      HCV genome. Various cell-based systems confirmed that let-7b plays a negative
      role in HCV expression. In particular, let-7b suppressed HCV replicon activity
      and down-regulated HCV accumulation leading to reduced infectivity of HCVcc.
      Mutational analysis identified let-7b binding sites at the coding sequences of
      NS5B and 5'-UTR of HCV genome that were conserved among various HCV genotypes. We
      further demonstrated that the underlying mechanism for let-7b-mediated
      suppression of HCV RNA accumulation was not dependent on inhibition of HCV
      translation. Let-7b and IFNalpha-2a also elicited a synergistic inhibitory effect
      on HCV infection. Together, let-7b represents a novel cellular miRNA that targets
      the HCV genome and elicits anti-HCV activity. This study thereby sheds new
      insight into understanding the role of host miRNAs in HCV pathogenesis and to
      developing a potential anti-HCV therapeutic strategy.

PMID- 22391674
TI  - Diffusion tensor imaging (DTI) study of a trigeminal neuralgia due to large
      venous angioma.

PMID- 22391673
TI  - Life on a microarray: assessing live cell functions in a microarray format.
AB  - Microarray technology outgrew the detection of simple intermolecular
      interactions, as incubation of slides with living cells opened new vistas. Cell
      based array technology permits simultaneous detection of several different cell
      surface molecules, allowing the complex characterization of cells with an amount
      of information that is hardly assessed by any other technique. Furthermore,
      binding of cells to printed antibodies or ligands may induce their activation,
      and consequently the outcome of these interactions, such as phosphorylation, gene
      expression, secretion of various products; differentiation, proliferation and
      apoptosis of the cells are also measurable on arrays. Moreover, since cells can
      be transfected with printed vectors, over- or under-expression of selected genes
      is also achievable simultaneously, creating a nice tool for assessing the
      function of a given gene. The enormously high-throughput cell-based microarray
      technology enables testing the effect of external stimuli on a scale that was
      earlier unthinkable. This review summarizes the possible applications of cell
      based arrays.

PMID- 22391675
TI  - Effects of topiramate use on body composition and resting metabolic rate in
      migraine patients.
AB  - Topiramate is an anticonvulsant agent effective in the prophylaxis of migraine,
      which also induces weight reduction by an unknown mechanism. We investigated the
      effect of topiramate on resting metabolic rate, anthropometric measurements, and
      body composition in patients with migraine independently from any intention to
      lose body weight. Forty patients (18-71 years old) with migraine were treated
      with 100 mg of topiramate/day over a period of 3 months. Anthropometric
      measurements, body fat proportions and resting metabolic rates of these patients
      were measured before and after treatment. At the end of 3 months, we detected
      mean 0.8 kg reduction in body weight and 0.3 kg/m(2) reduction in body mass index
      (BMI). Waist circumference decreased significantly (p = 0.01). Body fat ratio
      decreased (p = 0.016). Abdominal skinfold measurements decreased after treatment
      (p = 0.048); however, no difference was found in other regions (p > 0.05). We did
      not find a significant difference in resting metabolic rate (p > 0.05).These TPM
      treated patients lost weight and had reduction in their mean BMI. It was seen
      that patients lost weight from body fat tissue and central area. We saw that
      TPM'S weight-reducing effect was independent from resting metaobolic rate. The
      weight-reducing effect of TPM may result from changes on the hypothalamus.

PMID- 22391677
TI  - Effect of acupuncture on hippocampal Ref-1 expression in cerebral multi
      infarction rats.
AB  - Redox effector factor (Ref-1) is a sensitive marker for oxidative cellular
      injury. The aim of this study was to investigate the effects of acupuncture on
      hippocampal Ref-1 expression in cerebral multi-infarction rats. The rats with
      reference memory impairment were randomly allocated to three groups: impaired
      group, acupuncture group and placebo acupuncture group. Moreover, normal group
      and sham-operated group were set as control groups. Morris water maze test showed
      that cerebral multi-infarction rats did not present significant changes in
      spatial working memory performance. Further investigation by immunohistochemistry
      revealed that acupunctural treatment significantly increased the expression of
      Ref-1 in the hippocampus of the impaired rats. These findings suggested that the
      spatial working memory was unaffected in the cerebral multi-infarction rats
      although spatial reference memory deficits were detected in our previous study;
      in addition, acupuncture could increase the Ref-1 expression, consequently
      exerting the anti-oxidant effects.

PMID- 22391678
TI  - Multichannel fenestration of the petrous and cavernous segments of the internal
      carotid artery associated with two small carotid canals.

PMID- 22391676
TI  - Nature and nurture in stuttering: a systematic review on the case of Moses.
AB  - Stuttering is a disturbance of normal fluency of speech whose pathophysiology is
      still not well understood. We investigated one of the most ancient speech
      disorders in the biblical person Moses who lived in approximately 1300 BC. To get
      the most complete medical and non-medical information on Moses, we did systematic
      searches in the Holy Bible using the Bible-Discovery v2.3(c) software (
      http://www.bible-discovery.com ) looking for verses containing the terms "Moses",
      "Stuttering" and "Stutter"; and in PubMed/Medline database for manuscripts having
      the terms "Moses", "Bible" and "Stuttering". From the Bible search, 742 verses
      were found, of which 23 were relevant; three additional verses were found by hand
      search. Six papers discussing Moses's pathology were found in the PubMed search.
      The analysis of ancient descriptions in the light of current research suggests
      that stuttering is the most likely pathology Moses had, with clear evidence for
      both genetic origin and environmental triggers. Further, it was found that Moses
      practiced some "sensory tricks" that could be used to relieve his speech disorder
      which are, to our knowledge, the first "tricks" that successfully modulated a
      movement disorder described in the medical literature.

PMID- 22391679
TI  - Proteomic identification of aldolase A as an autoantibody target in patients with
      atypical movement disorders.
AB  - We tried to identify the target/s of autoantibodies to basal ganglia neurons
      found in a patient with hyperkinetic movement disorders (HMD) characterized by
      rapid, rhythmic involuntary movements or spasms in both face and neck. Patient
      and control sera were used in Western blot to probe mouse brain homogenates. Two
      dimensional gel electrophoresis (2-DE) SDS-PAGE protein spots recognized by the
      patient's antibodies were excised and sequenced by mass spectrometry analysis,
      and the glycolytic enzyme aldolase A was identified as the antigen recognized by
      the patient's autoantibodies. To assess relevance and specificity of these
      antibodies to the identified targets as biomarkers of autoimmunity in movement
      disorders, autoantibody responses to the identified target were then measured by
      ELISA in various diseases of the central nervous system. Anti-aldolase A
      autoantibodies were associated mainly with HMD (7/17, 41%) and Parkinson's
      disease (4/30, 13%) patients, and undetectable in subjects with other
      inflammatory and non-inflammatory central nervous system diseases. We, thus,
      identified aldolase A as an autoantigen in a sub-group of patients with HMD, a
      clinically ill-defined syndrome. Anti-aldolase A antibodies may represent a
      useful biomarker of autoimmunity in HMD patients.

PMID- 22391681
TI  - Limb-specific training affects exercise hyperemia but not sympathetic
      vasoconstriction.
AB  - This study used cross-sectional and longitudinal training research designs to
      determine if (a) exercise hyperemia is enhanced in exercise-trained forearms and
      (b) sympathetic vasoconstriction of the trained forearm is attenuated
      (sympatholysis) during handgrip exercise. In the cross-sectional comparison, 10
      rock climbers, 10 runners, 10 controls participated while the longitudinal
      training study examined vascular responsiveness in six untrained men before and
      after 6 weeks of handgrip training. Mean blood velocity, brachial artery
      diameter, heart rate, and systemic blood pressure were measured at rest, during a
      cold pressor test (CPT), dynamic handgrip exercise at 30% MVC with and without
      CPT, and during reactive hyperemia. During the resting CPT, forearm blood flow
      (FBF) decreased less (P < 0.05) in runners than in climbers, the decline being 
      6.30 + 30.05 and -34.3 + 20.54 during the last minute, respectively. During
      handgrip exercise, FBF and vascular conductance (VC) increased more (P < 0.05) in
      climbers than in runners and controls, the latter reaching 3.98 + 1.11, 2.22 +
      0.88, and 2.75 + 1.06 ml min(-1) mmHg(-1), respectively. When a CPT was added
      during handgrip exercise, the reduction in FBF and VC was not different between
      the groups. Handgrip training increased (P < 0.05) forearm volume (5 + 3%) and
      MVC (25 + 29%), but did not affect FBF or VC during a CPT, with or without
      exercise. These data suggest that arm-trained athletes have greater exercise
      hyperemia. However, this training effect is not explained by sympatholysis and is
      not evident after 6 weeks of handgrip training in previously untrained subjects.

PMID- 22391680
TI  - Osteoporotic vertebral compression fracture augmentation by injectable partly
      resorbable ceramic bone substitute (CeramentTM|SPINESUPPORT): a prospective
      nonrandomized study.
AB  - INTRODUCTION: This study aimed to evaluate long-term stabilizing healing
      effectiveness and influence on adjacent intact vertebral bodies of a new
      injectable partly resorbable calcium sulfate (60 wt.%)/hydroxyapatite (40 wt.%)
      bone substitute employed in vertebral augmentation of osteoporotic collapses.
      METHODS: From April 2009 to April 2011, 80 patients underwent vertebral
      augmentation. Patient enrolment criteria are as follows: age more than 20 years;
      symptomatic osteoporotic vertebral compression fracture from low energy trauma
      encompassing level T5 to L1 and classified as A1.1 to A1.2 according to the AO
      classification system; vertebral height compression within 0-75% compared to the
      posterior (dorsal) wall; client history confirming the age of the compression
      fracture to be within at least 4 weeks; and patients who are able to understand
      the procedure and participate in the study. Preoperative and postoperative
      imaging studies consisted of computed tomography, plain X-ray, dual X-ray
      absorptiometry scanning, and magnetic resonance. Pain intensity has been
      evaluated by an 11-point visual analog scale (VAS), and physical and quality of
      life compromise assessments have been evaluated by Oswestry Disability
      Questionnaire (ODI). All procedures have been performed fluoroscopically guided
      by left unilateral approach under local anesthesia and mild sedation. RESULTS:
      VAS-based pain trend over 12-month follow-up has shown a statistical significant
      (p < 0.001) decrease, starting from 7.68 (SD 1.83) preoperatively with an
      immediate first day decrease at 3.51 (SD 2.16) and 0.96 (SD 0.93) at 12 months.
      The ODI score dropped significantly from 54.78% to 20.12% at 6 months. None
      device-related complication has been reported. In no case, a new incidental
      adjacent fracture has been reported. CONCLUSION: Data show how this injectable
      partly resorbable ceramic cement could be a nontoxic and lower stiffness
      alternative to polymethylmethacrylate for immediate and long-term stabilization
      of osteoporotic collapsed vertebral bodies.

PMID- 22391682
TI  - Reduced plantar cutaneous sensation modifies gait dynamics, lower-limb kinematics
      and muscle activity during walking.
AB  - Peripheral neuropathy is the most common long-term complication in diabetes and
      is involved in changes in diabetic gait and posture. The regression of nerve
      function leads to various deficits in the sensory and motor systems, impairing
      afferent and efferent pathways in the lower extremities. This study aimed to
      examine how reduced plantar-afferent feedback impacts the gait pattern. Cutaneous
      sensation in the soles of both feet was experimentally reduced by means of
      intradermal injections of an anaesthetic solution, without affecting foot
      proprioception or muscles. Ten subjects performed level walking at a controlled
      velocity before and after plantar anaesthesia. Muscle activity of five leg
      muscles, co-contraction ratios for the knee and ankle joint, ground reaction
      forces (GRF), spatiotemporal characteristics, joint angles and moments of the
      hip, knee and ankle were analysed. The intervention significantly lowered plantar
      sensation, reducing it to the level of sensory neuropathy. Spatiotemporal gait
      characteristics remained unchanged. The ankle joint was more dorsiflexed which
      coincided with increased tibialis anterior and decreased gastrocnemius medialis
      muscle activity during foot flat to mid-stance. In addition, the knee joint was
      more flexed accompanied by increased biceps femoris activity and higher internal
      knee-extension moment. With regard to gait dynamics, a delay of the first peak of
      the vertical GRF was observed. Increased soleus and tibialis anterior muscle
      activity were found during the end of stance. Short-term loss of plantar
      sensation affects lower-limb kinematics and gait dynamics, particularly during
      the first half of stance, and contributes to modified muscle-activation patterns
      during locomotion.

PMID- 22391683
TI  - Redox balance and mitochondrial glycerol phosphate dehydrogenase activity in
      trained rats.
AB  - Free radical production is increased in many disease states and during exercise,
      but in the latter the concurrent stimulation of the antioxidant defense system
      seems to protect the organism from excessive production of reactive oxygen
      species. Chronic exercise can exert negative effects on the activity of
      mitochondrial glycerol phosphate dehydrogenase (mGPdH), which may offer some
      explanation for the antioxidant effects of training, since this enzyme is a
      relevant producer of free radicals. To test this correlation, we compared mGPdH
      activity, two antioxidant defense markers and two markers of oxidative stress in
      sedentary and trained (Tr) rats. Training was through a swimming exercise 3 days
      a week. After 8 weeks, Tr rats lasted twice as long as controls in an acute
      swimming test with a 5% load. Forty-eight hours after the last exercise, the
      animals were killed to collect blood and tissues. Tr animals presented lower body
      weight and visceral fat mass with lower triglyceride content in visceral fat and
      plasma (p < 0.05). The specific activity of mGPdH in muscle mitochondria was
      reduced in Tr rats by 88% (p < 0.05). Total antioxidant capacity, lipid
      peroxidation and reduced glutathione (GSH) in liver and muscle were unaltered,
      while plasma GSH increased by 21% (p < 0.05). These data suggest a profile of
      successful redox equilibrium maintenance in Tr rats, with a potentially
      significant contribution from the lower level of mGPdH activity in muscle. This
      training protocol appears to be suitable for use in detailed studies of
      biochemical adaptations to oxidative stress.

PMID- 22391684
TI  - Evaluation of the effects of hyperbaric oxygen therapy for spinal cord lesion in
      correlation with the moment of intervention.
AB  - STUDY DESIGN: Experimental, controlled, animal study. OBJECTIVES: To evaluate the
      functional effect of hyperbaric oxygen therapy administered shortly, one day
      after, and no intervention (control) in standardized experimental spinal cord
      lesions in Wistar rats. SETTING: Sao Paulo, Brazil. METHODS: In all, 30 Wistar
      rats with spinal cord lesions were divided into three groups: one group was
      submitted to hyperbaric oxygen therapy beginning half an hour after the lesion
      and with a total of 10 one-hour sessions, one session per day, at 2 atm; the
      second received the same treatment, but beginning on the day after the lesion;
      and the third received no treatment (control). The Basso, Beattie and Bresnahan
      scales were used for functional evaluation on the second day after the lesion and
      then weekly, until being killed 1 month later. RESULTS: There were no significant
      differences between the groups in the functional analysis on the second day after
      the lesion. There was no functional difference comparing Groups 1 and 2 (treated
      shortly after or one day after) in any evaluation moment. On the 7th day, as well
      as on the 21st and 28th postoperative days, the evaluation showed that groups 1
      and 2 performed significantly better than the control group (receiving no
      therapy). CONCLUSION: Hyperbaric chamber therapy is beneficial in the functional
      recovery of spinal cord lesions in rats, if it is first administered just after
      spinal cord injury or within 24 h.

PMID- 22391685
TI  - An investigation of seasonal variation in leisure-time physical activity in
      persons with spinal cord injury.
AB  - STUDY DESIGN: Secondary cross-sectional analyses of a cohort. OBJECTIVES: To
      examine seasonal variation in total moderate-to-vigorous leisure-time physical
      activity (MV-LTPA), exercise and sport participation in a cohort of individuals
      with spinal cord injury (SCI). SETTING: Community (Ontario, Canada). METHODS:
      Participants with SCI (n=695) completed telephone interviews regarding their
      involvement in MV-LTPA along with social cognitive predictors of MV-LTPA.
      Logistic regression was used to predict the impact of season on participation in
      MV-LTPA, exercise and sport. Hierarchical linear regression was used to examine
      seasonal variation in min per day of MV-LTPA in the active sub-cohort (n=342)
      with a specific focus on exercise (for example, wheeling), and sport (for
      example, sledge hockey). RESULTS: Logistic regressions revealed that season did
      not predict whether participants engaged in MV-LTPA, exercise or sport. Linear
      regressions revealed that individuals in the active sub-cohort who completed the
      questionnaire during the winter reported engaging in less MV-LTPA than those who
      were interviewed in summer (betasummer=0.14, P<0.05). This pattern was observed
      for exercise (betasummer=0.16, P<0.05; R2 change=0.018) but not for sport
      (betasummer=0.076, P=0.68; R2 change=0.014). CONCLUSION: Individuals with SCI
      report less exercise and total LTPA accrued during the winter months; sport was
      found to be an exception to this case.

PMID- 22391686
TI  - Burden and quality of life among caregivers of children and adolescents with
      meningomyelocele: measuring the relationship to anxiety and depression.
AB  - OBJECTIVES: This study aimed to assess the burden and quality of life (Qol) of
      primary caregivers of children/adolescents with meningomyelocele, taking into
      account the relationship to anxiety and depression symptoms. METHODS: A cross
      sectional approach was taken to analyze the health-related Qol and burden using
      the Short Form-36 Survey (SF-36) and the caregiver burden scale (CBS),
      respectively. Depressive and anxiety symptoms were investigated using the Beck
      Inventories. The Heckman two-step method was used to deal with the selection bias
      problem. RESULTS: A total of 43 primary caregivers were enrolled in the study.
      Most of the caregivers were mothers with preliminary education, living in
      consensual union. Lower scores in general health and vitality were reported in
      the SF-36. The mean global CBS score was 2.2. Majority of the volunteers (55.8%)
      were considered non-depressive. There were both positive and negative
      correlations between the scores of both Beck Inventories and most dimensions of
      the CBS and SF-36. The Heckman method showed a higher burden among caregivers who
      had children with fecal incontinence, were living together with a partner, were
      unemployed and had lower income (P<0.05). CONCLUSION: The primary caregivers of
      children and adolescents with myelomeningocele reported burden and a lower Qol.
      There were more anxiety and depression symptoms in subjects with higher burden
      and impaired Qol. Caregivers had a higher burden if they were living together
      with a partner, were unemployed, had low income and had care recipients with
      fecal incontinence.

PMID- 22391687
TI  - Influence of the neurological level of spinal cord injury on cardiovascular
      outcomes in humans: a meta-analysis.
AB  - BACKGROUND: Although motor and sensory deficits following spinal cord injury
      (SCI) are well known, there are still contrasting reports on how SCI affects
      baseline cardiovascular (CV) parameters and other autonomic functions. STUDY
      DESIGN: Meta-analysis is performed. OBJECTIVES: To examine the effect of injury
      level on supine and seated CV function in individuals with SCI. METHODS: A total
      of 98 studies representing 1968 individuals were retrieved for analysis. Systolic
      blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were
      abstracted from the studies and compared between four groups according to the
      neurological lesion level, cervical (C) SCI (C4-C8), high-thoracic (HT) SCI (T1
      T6), low-thoracic lumbar (LTL) SCI (below T6) and able-bodied (AB) controls.
      RESULTS: In the supine position, SBP, DBP and HR were lower in C compared with
      HT, LTL and AB (all P<0.04). In the seated position, SBP and DBP were
      significantly lower in C compared with LTL and AB (all P<0.003) and HR was
      significantly lower in C compared with LTL only (P=0.01). A final finding was
      that C exhibited a lower resting SBP in the seated compared with the supine
      position (P<0.001). CONCLUSION: Individuals with SCI exhibit a lesion-dependent
      impairment in resting CV function, whereby those with the highest injury had the
      greatest degree of CV dysfunction. A further finding was that individuals with a
      C injury exhibited a lower resting SBP in the seated vs supine position. Thus,
      clinicians and researchers should consider lesion level and body position when
      measuring and interpreting CV parameters in individuals with SCI.

PMID- 22391688
TI  - Fitness, fatness and survival in elderly populations.
AB  - This study examines the relative importance of fitness versus fatness in
      predicting mortality in elderly populations aged 70 years and over, and whether
      fitness may account for the 'paradoxical' relationship between better survival
      and increasing weight. Four thousand community-living Chinese men and women aged
      65 years or over were recruited and stratified so that approximately 33% were in
      each of the age groups: 65-69, 70-74, and 75 or above. Medical history, height,
      weight, waist-hip ratio, body composition using DEXA, and walking speed were
      obtained. They were followed up for a mean of 7.0 years to ascertain death.
      Compared with the high fitness category, those in the moderate and low categories
      have a 43% and 68% increased risk of mortality at 7 years adjusting for multiple
      confounders. When mortality risk according to various fatness indicators was
      examined, only the lowest quartile of BMI, BFI, and FLMR conferred statistically
      significant increased risk. Fitness categories were significantly associated with
      all fatness indicators. The finding of fewer people in the high fitness category
      among the highest quartiles of other fatness indicators suggests that fitness is
      not the underlying mechanism for the obesity paradox. Within each quartile of
      fatness indicator, there was a significant trend towards reduced mortality with
      increasing fitness. In conclusion, the study confirms the beneficial effects of
      cardiorespiratory fitness on mortality but does not explain the 'obesity
      paradox'. The findings underscore the importance of maintaining physical fitness
      through exercise and re-confirm the importance of weight maintenance in reducing
      mortality risk.

PMID- 22391689
TI  - Oil palm empty fruit bunch as alternative substrate for acetone-butanol-ethanol
      production by Clostridium butyricum EB6.
AB  - Acetone-butanol-ethanol (ABE) production from renewable resources has been widely
      reported. In this study, Clostridium butyricum EB6 was employed for ABE
      fermentation using fermentable sugar derived from treated oil palm empty fruit
      bunch (OPEFB). A higher amount of ABE (2.61 g/l) was produced in a fermentation
      using treated OPEFB as the substrate when compared to a glucose based medium that
      produced 0.24 g/l at pH 5.5. ABE production was increased to 3.47 g/l with a
      yield of 0.24 g/g at pH 6.0. The fermentation using limited nitrogen
      concentration of 3 g/l improved the ABE yield by 64%. The study showed that OPEFB
      has the potential to be applied for renewable ABE production by C. butyricum EB6.

PMID- 22391690
TI  - Production of microbial cellulose by a bacterium isolated from fruit.
AB  - This study presents the production of bacterial cellulose (BC) by a bacterium
      isolated from a rotten fruit and its process optimization. Here, isolation and
      screening of potent cellulose producers were carried out from different natural
      sources, viz., soil, rotten fruits, and vegetables and vinegar. A total of 200
      bacterial isolates were obtained, which were screened for cellulose production
      using Hestrin-Schramm medium. A novel and potent cellulose-producing bacterium
      was newly isolated from a rotten fruit and identified as Gluconacetobacter sp. F6
      through 16S ribosomal DNA sequencing and morphological, cultural, and biochemical
      characteristics. After optimization of culture conditions, including pH,
      temperature, agitation, carbon/nitrogen sources, and inducers, the BC production
      was greatly increased from 0.52 to 4.5 g/l (8.65-fold increase). The optimal
      culture medium contained 1% (w/v) glucose, 1.5% (w/v) yeast extract, 0.5% (w/v)
      peptone, 0.27% (w/v) disodium hydrogen phosphate, 0.115% (w/v) citric acid, and
      0.4% (w/v) ethanol. BC produced was analyzed for the presence of cellulose
      fibrils by epiflourescent microscopy using Calcofluor white stain and scanning
      electron microscopy and confirmed by NMR. There are very scanty reports about the
      optimization of BC production by bacteria isolated from rotten fruits.

PMID- 22391691
TI  - Production of microbial surfactants from oily sludge-contaminated soil by
      Bacillus subtilis DSVP23.
AB  - The indigenous microbial community utilizing aliphatic, aromatic, and polar
      components from the oily sludge as sole source of carbon and energy was selected
      from the soil samples of Ankleshwar, India for biosurfactant production.
      Evaluation of biosurfactant production was done using screening assays such as
      surface tension reduction, hemolytic activity, emulsification activity, drop
      collapse assay, and cell surface hydrophobicity studies. Maximum biosurfactant
      (6.9 g/l) production was achieved after 5 days of growth from Bacillus subtilis
      DSVP23 which was identified by 16S RNA technique (NCBI GenBank accession no.
      EU679368). Composition of biosurfactant showed it to be lipopeptide in nature
      with 15.2% protein content and 18.0% lipid content. Functional group analysis was
      also done by using Fourier transform infrared spectroscopy which showed it to be
      a protein-bound lipid thereby imparting them special properties. Analysis by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometric and
      nuclear magnetic resonance revealed that the major constituents of lipopeptide
      are leucine and isoleucine. Gas chromatographic analysis data indicated that oily
      sludge components of chain length C12-C30 and aromatic hydrocarbons were degraded
      effectively by B. subtilis DSVP23 after 5 days of incubation. These results
      collectively points toward the importance of B. subtilis DSVP23 as a potential
      candidate for bioremediation studies.

PMID- 22391692
TI  - Generation of monoclonal antibody for 15-deoxy-Delta12,14-prostaglandin J2 and
      development of enzyme-linked immunosorbent assay for its quantification in
      culture medium of adipocytes.
AB  - 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) is a biologically active molecule
      serving as a pro-adipogenic factor or an anti-inflammatory regulator. This
      compound is one of naturally occurring derivatives formed by the non-enzymatic
      dehydration of PGD2. To determine the endogenous synthesis of 15d-PGJ2, a
      convenient immunological approach is useful. At first, we established a cloned
      hybridoma cell line to secrete a monoclonal antibody specific for 15d-PGJ2. For
      the development of a solid-phase enzyme-linked immunosorbent assay (ELISA), the
      immobilized antigen using a protein conjugate of 15d-PGJ2 was allowed to react
      competitively with a monoclonal antibody in the presence of free 15d-PGJ2. Under
      the optimized conditions, a sensitive calibration curve was generated able to
      determine the amount of 15d-PGJ2 from 0.5 pg to 9.7 ng with 71 pg of 50%
      displacement in one assay. Our monoclonal antibody did not recognize other
      related prostanoids except PGJ2 with cross-reaction of 4%. Our ELISA was
      demonstrated to be reliable for the quantification of 15d-PGJ2 in the maturation
      medium of cultured adipocytes by confirming the accuracy and specificity of its
      determination. The application of our assay revealed that the non-enzymatic
      formation of 15d-PGJ2 became more evident after several hours of incubation with
      authentic PGD2 at 37  degrees C. The results indicate the usefulness of our
      developed solid-phase ELISA with the monoclonal antibody for further studies on
      the endogenous synthesis of 15d-PGJ2 and its roles in various cells and tissues.

PMID- 22391693
TI  - Advances and developments in strategies to improve strains of Saccharomyces
      cerevisiae and processes to obtain the lignocellulosic ethanol--a review.
AB  - The conversion of biomass into ethanol using fast, cheap, and efficient
      methodologies to disintegrate and hydrolyse the lignocellulosic biomass is the
      major challenge of the production of the second-generation ethanol. This revision
      describes the most relevant advances on the conversion process of lignocellulose
      materials into ethanol, development of new xylose-fermenting strains of
      Saccharomyces cerevisiae using classical and modern genetic tools and strategies,
      elucidation of the expression of some complex industrial phenotypes, tolerance
      mechanisms of S. cerevisiae to lignocellulosic inhibitors, monitoring and
      strategies to improve fermentation processes. In the last decade, numerous
      engineered pentose-fermenting yeasts have been developed using molecular biology
      tools. The increase in the tolerance of S. cerevisiae to inhibitors is still an
      important issue to be exploited. As the industrial systems of ethanol production
      operate under non-sterile conditions, microbial subpopulations are generated,
      depending on the operational conditions and the levels of contaminants. Among the
      most critical requirements for production of the second-generation ethanol is the
      reduction in the levels of toxic by-products of the lignocellulosic hydrolysates
      and the production of low-cost and efficient cellulosic enzymes. A number of
      procedures have been established for the conversion of lignocellulosic materials
      into ethanol, but none of them are completely satisfactory when process time,
      costs, and efficiency are considered.

PMID- 22391694
TI  - Topoisomerase inhibition, nucleolytic and electrolytic contribution on DNA
      binding activity exerted by biological active analogue of coordination compounds.
AB  - The neutral mononuclear copper complexes with the quinolone antibacterial drug
      ciprofloxacin and bipyridine derivatives have been synthesized and characterized.
      Complexes were screened for their antibacterial activity against three Gram((-))
      and two Gram((+)) bacteria, and study suggests inhibition of gyrase activity by
      metal complexes as the possible mechanism. The nucleolytic activity of adducts
      was carried out on double stranded pUC19 DNA using gel electrophoresis in the
      presence of radical scavenging agents that suggest hydrolytic cleavage mechanism
      for plasmid DNA.

PMID- 22391695
TI  - Angiotensin I-converting enzyme inhibitory proteins and peptides from the
      rhizomes of Zingiberaceae plants.
AB  - Ammonium sulphate cut protein extracts, and their pepsin hydrolysates, from the
      rhizomes of 15 plants in the Zingiberaceae family were screened for their in
      vitro angiotensin I-converting enzyme inhibitory (ACEI) activity. The protein
      extract from Zingiber ottensii had the highest ACEI activity (IC(50) of 7.30 *
      10(-7) mg protein/mL) and was enriched for by SP Sepharose chromatography with
      five NaCl step gradients 0, 0.25, 0.50, 0.75 and 1 M NaCl collecting the
      corresponding five fractions. The highest ACEI activity was found in the F75
      fraction, which appeared to contain a single 20.7-kDa protein, suggesting
      enrichment to or near to homogeneity. The ACEI activity of the F75 fraction was
      moderately thermostable (-20-60  degrees C), showed >80% activity across a broad
      pH range of 4-12 (optimal at pH 4-5) and appeared as a competitive inhibitor of
      ACE (K(i) of 9.1 * 10(-5) mg protein/mL). For the pepsin hydrolysates, that from
      Zingiber cassumunar revealed the highest ACEI activity (IC(50) of 0.38 +/- 0.012
      mg/mL), was enriched to a single active hexapeptide by RP-HPLC with a strong ACEI
      activity (IC(50) of 0.011 +/- 0.012 mg/mL) and acted as a competitive inhibitor
      of ACE (K(i) of 1.25 * 10(-6) mg protein/mL).

PMID- 22391696
TI  - Initial proteome analysis of caffeine-induced proteins in Aspergillus tamarii
      using two-dimensional fluorescence difference gel electrophoresis.
AB  - Caffeine is toxic to most microorganisms. However, some filamentous fungi, such
      as Aspergillus tamarii, are able to metabolize this alkaloid when fed caffeine as
      the sole nitrogen source. The aim of the present work was to identify
      intracellular A. tamarii proteins, regulated by caffeine, using fluorescence
      difference two-dimensional gel electrophoresis. Specific proteins from two
      culture media of A. tamarii grown either on ammonium sulfate or caffeine as the
      sole nitrogen source were analysed by mass spectrometry. Thirteen out of a total
      of 85 differentially expressed spots were identified after database search.
      Identified up-regulated proteins include phosphoglycerate kinase, malate
      dehydrogenase, dyp-type peroxidase family protein, heat shock protein, Cu, Zn
      superoxidase dismutase and xanthine dehydrogenase. Some of the proteins
      identified in this study are involved in the caffeine degradation pathway as well
      as in stress response, suggesting that stress proteins could be involved in
      caffeine metabolism in filamentous fungi.

PMID- 22391697
TI  - The impact of long-term in vitro expansion on the senescence-associated markers
      of human adipose-derived stem cells.
AB  - Human adipose-derived stem cells (ASCs) have generated a great deal of excitement
      in regenerative medicine. However, their safety and efficacy issue remain a major
      concern especially after long-term in vitro expansion. The aim of this study was
      to investigate the fundamental changes of ASCs in long-term culture by studying
      the morphological feature, growth kinetic, surface marker expressions, expression
      level of the senescence-associated genes, cell cycle distribution and beta
      galactosidase activity. Human ASCs were harvested from lipoaspirate obtained from
      6 patients. All the parameters mentioned above were measured at P5, P10, P15 and
      P20. Data were subjected to one-way analysis of variance with a Tukey post hoc
      test to determine significance difference (P < 0.05). The data showed that growth
      of ASCs reduced in long-term culture and the beta-galactosidase activity was
      significantly increased at later passage (P20). The morphology of ASCs in long
      term culture showed the manifestation of senescent feature at P15 and P20.
      Significant alteration in the senescence-associated genes expression levels was
      observed in MMP1, p21, Rb and Cyclin D1 at P15 and P20. Significant increase in
      CD45 and HLA DR DQ DP surface marker was observed at P20. While cell cycle
      analysis showed significant decrease in percentage of ASCs at S and G2/M phase at
      later passage (P15). Our data showed ASCs cultured beyond P10 favours the
      senescence pathway and its clinical usage in cell-based therapy may be limited.

PMID- 22391698
TI  - A superoxide dismutase purified from the rhizome of Curcuma aeruginosa Roxb. as
      inhibitor of nitric oxide production in the macrophage-like RAW 264.7 cell line.
AB  - Superoxide dismutase (SOD, EC 1.15.1.1) is a metalloenzyme or antioxidant enzyme
      that catalyzes the disproportionation of the harmful superoxide anionic radical
      to hydrogen peroxide and molecular oxygen. Due to its antioxidative effects, SOD
      has long been applied in medicinal treatment, cosmetic, and other chemical
      industries. Fifteen Zingiberaceae plants were tested for SOD activity in their
      rhizome extracts. The crude homogenate and ammonium sulfate cut fraction of
      Curcuma aeruginosa were found to contain a significant level of SOD activity. The
      SOD enzyme was enriched 16.7-fold by sequential ammonium sulfate precipitation,
      diethylaminoethyl cellulose ion exchange, and Superdex 75 gel filtration column
      chromatography. An overall SOD yield of 2.51 % with a specific activity of 812.20
      U/mg was obtained. The enriched SOD had an apparent MW of 31.5 kDa, as judged by
      sodium dodecyl sulfate polyacrylamide gel electrophoresis, and a pH and
      temperature optima of 4.0 and 50  degrees C. With nitroblue tetrazolium and
      riboflavin as substrates, the K(m) values were 57.31 +/- 0.012 and 1.51 +/- 0.014
      M, respectively, with corresponding V(max) values of 333.7 +/- 0.034 and 254.1 +/
      0.022 MUmol min(-1) mg protein(-1). This SOD likely belongs to the Fe- or Mn-SOD
      category due to the fact that it was insensitive to potassium cyanide or hydrogen
      peroxide inhibition, but was potentially weakly stimulated by hydrogen peroxide,
      and stimulated by Mn(2+)and Fe(2+) ions. Moreover, this purified SOD also
      exhibited inhibitory effects on lipopolysaccharide-induced nitric oxide
      production in cultured mouse macrophage cell RAW 264.7 in a dose-dependent manner
      (IC(50) = 14.36 +/- 0.15 MUg protein/ml).

PMID- 22391699
TI  - Prostate-specific antigen velocity versus prostate-specific antigen doubling time
      for prediction of 11C choline PET/CT in prostate cancer patients with biochemical
      failure after radical prostatectomy.
AB  - PURPOSE: We previously showed that prostate-specific antigen (PSA) doubling time
      (PSADT) is a significant predictor of 11C choline positron emission
      tomography/computed tomography (PET/CT) findings in prostate cancer (PCa)
      patients. This study compared PSA velocity (PSAV) and PSADT to predict 11C
      choline PET/CT findings. MATERIALS AND METHODS: PSAV and PSADT were
      retrospectively calculated in 170 PCa patients with biochemical failure after
      radical prostatectomy, who underwent 11C choline PET/CT for restaging of disease.
      RESULTS: Median PSA was 1.25 ng/mL (range: 0.23-48.6 ng/mL), and median PSAV was
      0.99 ng/mL/y (range: 0.11-98.9 ng/mL/y). Patients with positive 11C choline
      PET/CT (n = 75) had significantly (P < 0.05) higher PSAV than patients with
      negative 11C choline PET/CT (n = 95) (6.93 +/- 13.08 vs. 1.23 +/- 2.03 ng/mL/y).
      The percent of patients with positive 11C choline PET/CT was 21% for PSAV <1
      ng/mL/y, 56% for PSAV between 1 and 2 ng/mL/y, and 76% for PSAV >2 ng/mL/y. The
      quality of fitting (r2) of PSA values according to the exponential function
      (PSADT) was significantly (P < 0.05) better than the quality of fitting according
      to the linear function (PSAV) in the entire sample and in all anatomic regions.
      At multivariate analysis, trigger PSA, PSADT but not PSAV obtained the
      statistical significance (P < 0.05). CONCLUSIONS: PSAV can be used to stratify
      the risk of positive 11C choline PET/CT in PCa patients with biochemical failure.
      Patients with PSAV >1 ng/mL/y should be selected to increase the positive
      detection rate of 11C choline PET/CT. The greater statistical power of PSADT
      compared with PSAV could be related to the better capability of fitting time
      dependent changes in PSA values, thereby better reflecting the natural growth of
      recurrent PCa.

PMID- 22391700
TI  - Comparative accuracy of CT attenuation-corrected and non-attenuation-corrected
      SPECT myocardial perfusion imaging.
AB  - OBJECTIVE: The aim of the present study was to evaluate whether computed
      tomography based-attenuation correction (CT-AC) provides any advantage over non
      attenuation-corrected (NAC) images for qualitative and quantitative analysis of
      single photon emission tomography (SPECT) myocardial perfusion imaging (MPI).
      METHODS: We retrospectively evaluated data of 171 patients who underwent stress
      rest MPI SPECT/CT as per standard protocol. Angiography done within +/-3 months
      of MPI was taken as reference standard. Two readers independently evaluated CT-AC
      and NAC images. Receiver operating characteristic curve analysis was done using
      >=50% and >=70% stenosis as cutoff. The size and severity of perfusion defects
      were also compared on CT-AC and NAC images. RESULTS: For both readers, the area
      under the receiver operating characteristic curve was larger for CT-AC images
      than for NAC images at both >=50% and >=70% cutoff, but the difference was not
      significant. CT-AC images had significantly lower sensitivity for detecting right
      coronary artery disease compared with NAC (29% vs. 50% for reader 1 and 25.8% vs.
      43.2% for reader 2). However, the specificity improved with CT-AC. Inferior
      defects were significantly smaller in CT-AC than NAC (P = 0.0002), with no
      significant difference for anterior defects (P = 0.544). There was significant
      variation in severity between CT-AC and NAC images for both overall (P = 0.001)
      as well as for inferior defects (P = 0.0007), but not for anterior defects (P =
      0.279). CONCLUSION: In our study, the CT-based AC improved the specificity but
      decreased the sensitivity leading to nonsignificant improvement in overall
      diagnostic accuracy of Tc-99m sestamibi/tetrofosmin MPI.

PMID- 22391701
TI  - SPECT/CT in differentiation of pseudarthrosis from other causes of back pain in
      lumbar spinal fusion: report on 10 consecutive cases.
AB  - PURPOSE: SPECT fused with computed tomography (CT) provides a new approach for
      more accurate diagnosis of pseudathrosis after spinal fusion procedures. The aim
      of this study was to compare the findings of SPECT fused with CT (SPECT/CT) with
      those of CT alone for the diagnosis of pseudarthrosis. MATERIALS AND METHODS:
      SPECT and CT of 10 consecutive patients with recurrence of back and/or leg pain
      and with suspicion of pseudarthrosis on conventional radiologic imaging were
      analyzed retrospectively. All had previously undergone anterior and/or posterior
      lumbar fusion techniques. Presence of screw loosening, nonunion through or around
      the cages, and facet joint degeneration were assessed for diagnosis of
      pseudarthrosis. Based on SPECT/CT scan findings, the decision of surgical
      reintervention was made on 6 of 10 patients. The clinical follow-up (mean, 15.6
      months; range, 5-29 months) was evaluated according to Macnab criteria
      (excellent, good, fair, poor). RESULTS: All patients showing screw loosening on
      CT alone showed also an abnormal uptake on SPECT/CT. SPECT/CT did not show
      abnormal uptake in 3 of 5 patients who had nonunion through/around the cages on
      CT alone. SPECT/CT was able to show increased uptake in 6 cases in which CT alone
      did not show facet joint degeneration. CONCLUSIONS: In the lumbar spine, SPECT/CT
      seems to increase specificity for detection of nonunion of interbody devices
      compared with CT alone. It is more sensitive than CT to detect facet joint
      degeneration, and it can detect screw loosening as well as CT. These findings can
      be helpful for surgeons in planning appropriate surgical revision strategy.

PMID- 22391702
TI  - The use of molecular breast imaging to assess response in women undergoing
      neoadjuvant therapy for breast cancer: a pilot study.
AB  - PURPOSE OF THE REPORT: To report our findings from a prospective pilot study
      evaluating the accuracy of molecular breast imaging (MBI) in assessing tumor
      response to neoadjuvant therapy (NT) for breast cancer. MATERIALS AND METHODS:
      Twenty patients with newly diagnosed invasive breast cancer who were scheduled to
      receive NT underwent MBI before beginning and after completing NT before surgery.
      MBI was performed using a dual-detector cadmium-zinc-telluride gamma camera
      system mounted on a modified mammography gantry after patients had received an
      intravenous injection of 20 mCi of 99mTc sestamibi. Tumor extent was measured on
      MBI, and tumor-to-background (T/B) ratios of radiotracer uptake were determined
      through region-of-interest analysis. Pathologic measurement of tumor size was
      used as a standard and compared with post-NT tumor size derived from MBI.
      RESULTS: Three patients in whom post-NT MBI could not be performed because of
      scheduling problems were excluded from analysis. Eighteen cancers were diagnosed
      in 17 patients. A correlation coefficient of r = 0.681 (P = 0.002) was found
      between MBI and residual tumor size. The average T/B ratio on MBI decreased from
      a pretreatment value of 3.0 to a posttreatment value of 1.4. The relative
      decrease in T/B ratio did not appear to be predictive of response. CONCLUSIONS:
      Measurements of tumor size by MBI and T/B ratios are limited in their predictive
      value regarding the pathologic extent of residual disease in women treated with
      NT for breast cancer. Alternate tumor-specific radiopharmaceuticals should be
      evaluated to provide information to improve planning and monitoring of breast
      cancer treatment.

PMID- 22391703
TI  - Renal cortical imaging in children: 99mTc MAG3 versus 99mTc DMSA.
AB  - OBJECTIVE: To determine the potentials of technitium-99m mercaptoacetyltriglycine
      (99mTc MAG3) to replace technitium-99m dimercaptosuccinic acid (99mTc DMSA) in
      assessment of renal cortex and split renal function (SRF). MATERIAL AND METHODS:
      This a retrospective study in which we reviewed the scintigraphic results of 52
      patients with age range of 7 days-10 years (mean, 5.3 years). A total of 104
      studies (1 99mTc MAG3 and 1 99mTc DMSA per patient) were performed between 1
      January, 2009 and 31 December, 2010 because of various renal disorders. Both
      studies were performed within 24 hours of each other, starting with 99mTc MAG3.
      RESULTS: Twenty patients had normal SRF, and 26 patients had abnormal SRF (6 with
      solitary kidney, 4 with 1 kidney SRF <10%, and 16 with 1 kidney SRF >10%). In all
      46 patients, SRF assessed by 99mTc MAG3 correlated with that by 99mTc DMSA (P =
      0.0001). In remaining 6 patients, the correlation was less optimal, and the
      diseased kidney had overestimation of SRF by 99mTc MAG3. Nonvisualized kidneys
      and cortical defects were observed equally on both studies. CONCLUSION: 99mTc
      MAG3 provides adequate images for assessment of renal cortex and accurate
      measurement of SRF comparable with 99mTc DMSA results. In addition, it provides
      important information on the urodynamics of both kidneys, avoids unnecessary
      radiation to the children, as well as is time saving. We consider it is time to
      replace the 99mTc DMSA with 99mTc MAG3 in most nephrourologic disorders in
      pediatric patients and to keep the former to doubtful cases obtained using the
      latter.

PMID- 22391704
TI  - Automatic measurement of renal volume in children using 99mTc dimercaptosuccinic
      acid SPECT: normal ranges with body weight.
AB  - OBJECTIVE: The purpose of this study was to automate volume measurement of
      pediatric kidneys using Technetium-99m-dimercaptosuccinic acid (99mTc DMSA)
      SPECT. Assessment of renal size is essential in making an accurate clinical
      diagnosis and in evaluating normal and abnormal renal growth. Existing techniques
      for measuring renal length and volume are often observer-dependent and are
      limited by interobserver variability. MATERIALS AND METHODS: An automated method
      using 99mTc DMSA SPECT was developed to measure renal length, volume, and 2D/3D
      split renal functions. An adaptive threshold was used for segmentation of renal
      images. To improve measurement accuracy of renal volumes, a boundary-weighted
      integration and a linear correction from phantom experiments were applied. Using
      the new automated software, we evaluated 620 normal kidneys in 310 patients aged
      1 to 21 years. RESULTS: In all, 99.4% of renal volume measurement was inter
      /intraobserver reproducible without manual intervention. Correlations between
      renal size (volume and length) and growth parameters (age and body weight) were
      evaluated by nonlinear regression modeling. Body weight was found to be the best
      predictor of kidney volume and length (P < 0.0001). Normal ranges were
      established according to body weight. CONCLUSIONS: Automatic renal volume
      measurement with 99mTc DMSA SPECT demonstrates high observer reproducibility, and
      it is useful for achieving accurate assessment of renal growth using sequential
      measurements. The renal growth models generated by this study will aid physicians
      in evaluating and monitoring renal growth.

PMID- 22391705
TI  - Normal uptake of 68Ga-DOTA-TOC by the pancreas uncinate process mimicking
      malignancy at somatostatin receptor PET.
AB  - PURPOSE: To characterize a commonly occurring increased uptake by the uncinate
      process of the pancreas at PET/CT using 68Ga-DOTA-d-Phe1-Tyr3-octreotide (68Ga
      DOTA-TOC). This tracer has replaced In pentetreotide (OctreoScan(r)) for
      somatostatin receptor scintigraphy at our laboratory. METHODS: Fifty of our first
      74 PET/CT examinations with 68Ga-DOTA-TOC could be evaluated in retrospect. None
      of these patients had surgery or showed any pathology in the pancreas head at the
      concomitant CT. RESULTS: Thirty-five of the 50 examinations (70%) showed an
      uptake by the uncinate process sufficiently intense to be interpreted as
      pathologic and simulating a tumor. Mean SUVmax was 9.2. Mean SUVmean using an
      isoactivity cut-off of >75% and >50% was 7.8 and 6.0, respectively. Volume
      calculations of the uncinate process activity using these definitions gave 0.9 mL
      and 4.2 mL, respectively. CONCLUSION: There is a frequent physiological uptake of
      68Ga-DOTA-TOC by the pancreas uncinate process. This may be caused by an
      accumulation of pancreatic polypeptide-containing cells expressing somatostatin
      receptors. If there is a normal finding at concomitant diagnostic CT, this uptake
      should be regarded as physiological.

PMID- 22391706
TI  - Early dynamic PET/CT and 18F-FDG blood flow imaging in bladder cancer detection:
      a novel approach.
AB  - BACKGROUND: The standard PET/CT and 18F-FDG scanning protocols for patients with
      cancer call for data acquisitions to start 50 to 60 minutes postinjection (PI) of
      the radiopharmaceutical. This prolonged incubation period allows the
      concentration of high activity tracer to accumulate in the urinary bladder
      rendering identification of bladder lesions very difficult, if not impossible.
      The objective of this study was to identify bladder cancer using a novel PET/CT
      and 18F-FDG scanning protocol that takes advantage of the angiogenesis observed
      in malignancies and the kidneys' physiology of delayed excretion of 18F-FDG into
      the urinary bladder. METHODS: Early dynamic PET/CT and 18F-FDG scans were
      performed on 7 consecutive male patients with pathology-confirmed bladder cancer.
      A series of 5 dynamic scans of 2 minutes each, starting at injection time, were
      obtained on each patient's urinary bladder. Areas of increased 18F-FDG blood flow
      to the bladder walls were considered suspicious for cancer. RESULTS: Using
      pathologic report as the gold standard, this new protocol resulted in 5 true
      positives, 1 true negative, and 1 false positive. The average maximum standard
      uptake values (SUVmax +/- SD), at 2 to 4 minutes postinjection, of bladder wall
      areas with increased and normal blood flow were 2.7 +/- 0.7 and 1.1 +/- 1.3 g/mL,
      respectively. Also, the average activity concentration ratios (tumor/blood
      vessel) of suspected cancerous regions versus time showed a linear pattern with a
      slope of 2.9. CONCLUSION: Early dynamic FDG PET images can demonstrate bladder
      lesions that are obscured by urine activity on routine images at 1 hour.

PMID- 22391707
TI  - Communicating in organizations, part II: Tips for leaders when starting a team.
AB  - Team projects are an important part of the innovative work done in large
      organizations. Individuals from various portions of the department or
      organization are chosen who have different areas of expertise, backgrounds, and
      personalities. In a properly functioning team, the group decisions made will be
      superior to those made by any individual on the team. There are many different
      conversations that are necessary during a team project to make sure that all goes
      optimally, and this article will focus on communication tips for leaders when
      starting a team.

PMID- 22391708
TI  - Late splenosis evaluation after autoimplantation of spleen morsels in major
      omentum in hepatosplenic schistosomiasis patients using SPECT/CT imaging.

PMID- 22391709
TI  - Postoperative lymphocele demonstrated by lymphoscintigraphy SPECT/CT.

PMID- 22391710
TI  - 99mTc MAA pulmonary perfusion scintigraphy in 2 cases of anomalous systemic
      arterial supply to normal basal segments of the left lower lobe of the lung.

PMID- 22391711
TI  - 99mTc-MDP- and 18F-FDG-avid metastatic liver lesion: the similarities and
      differences between 2 modalities.

PMID- 22391712
TI  - 99mTc MAG3 renography demonstrating return to normal renal function following
      resolution of renal vein thrombosis.

PMID- 22391713
TI  - Waders sign on bone scan: a manifestation of portal hypertension.

PMID- 22391714
TI  - Myocardial perfusion scintigraphy after cardiac arrest: on the pathophysiology of
      cardiac death.

PMID- 22391715
TI  - 124I-anti-CD52 dosimetry before radioimmunotherapy as part of conditioning for
      stem cell transplantation in acute leukemia.

PMID- 22391716
TI  - Hepatocelluar carcinoma in an accessory lobe of the liver revealed by 11C-acetate
      PET with a negative finding on FDG imaging.

PMID- 22391717
TI  - Serial bone scintigraphy in a case of malignant epithelioid hemangioendothelioma.

PMID- 22391718
TI  - 18F-FDG and 11C-methionine PET/CT findings in a case with anti-NMDA (NR2B)
      receptor encephalitis.

PMID- 22391719
TI  - Localization of lymphatic leakage site in chylothorax by thoracic duct
      scintigraphy by orally administered 123I BMIPP using SPECT/CT.

PMID- 22391720
TI  - Perirenal urinoma on bone scan as the first manifestation of ureteral metastasis
      in a colon cancer patient.

PMID- 22391721
TI  - Unusual pelvic mass on bone scan caused by a preserved cranial bone graft.

PMID- 22391722
TI  - Lymphoscintigraphy of lower limb edema.

PMID- 22391723
TI  - Sarcomatoid carcinoma (carcinosarcoma) of the lung mimics malignant pleural
      mesothelioma on 18F-FDG PET/CT: a report of 2 cases.

PMID- 22391724
TI  - FDG uptake by a condylomata acuminata in an HIV-infected patient mimicked urine
      contamination.

PMID- 22391725
TI  - Current readings in nuclear medicine.

PMID- 22391726
TI  - 11C-acetate PET/CT in bladder urothelial carcinoma: intraindividual comparison
      with 11C-choline.
AB  - OBJECTIVE: We present a first study of the use of 11C-acetate (ACET) positron
      emission tomography (PET)/computed tomography (CT) in bladder urothelial
      carcinoma (UC) and an intraindividual comparison with 11C-choline (CHOL) PET/CT.
      METHODS: Fourteen patients with biopsy-proven UC (11 T2, 3 T1 refractory to
      treatment) were prospectively evaluated before radical cystectomy and excision of
      pelvic lymph nodes (LNs), with ACET and CHOL PET/CT scans performed within 1
      week. Image acquisition started 5 minutes after intravenous injection of 12 to 14
      mCi for both tracers. Standardized uptake values (SUVs) and tumor-to-background
      ratios (TBR) were calculated for all tumor and nodal findings and correlated with
      histopathology and follow-up. RESULTS: ACET and CHOL were taken up in all UCs,
      involved LNs, and prostate pathology. SUVs were on average slightly,
      nonsignificantly higher for CHOL uptake (SUV) in UCs and significantly higher for
      ACET in LNs. TBR was nonsignificantly higher with CHOL for UC and significantly
      higher for LNs. CONCLUSIONS: In this preliminary series, 11C-ACET and 11C-CHOL
      PET/CT showed equivalent results in the preoperative evaluation of UC. Both
      tracers have the potential to contribute to selecting patients who would benefit
      from combined treatment--neoadjuvant chemotherapy and surgery--by identifying
      pathologic LNs or from surgery only, thanks to their high negative predictive
      value for LN involvement.

PMID- 22391727
TI  - 18F-DOPA PET/CT in neuroblastoma: comparison of conventional imaging with CT/MR.
AB  - AIM: Role of 18F-DOPA PET/CT in neuroblastoma (NB) compared with CT/MR. MATERIALS
      AND METHODS: In all, 21 patients (M:F = 14:7; mean age, 7.4 years) affected by
      advanced stage NB (III-IV) were prospectively enrolled. Overall, 37 paired 18F
      DOPA PET and CT/MR scans were performed, and for each, we identified site and
      number of lesions. Standard of reference was based on a multidisciplinary
      assessment, including 123I-MIBG, selective biopsy, and clinical-instrumental
      monitoring. Both scan-based and a lesion-based analysis was performed, and for
      each modality, we calculated sensitivity, specificity, negative predictive value
      (NPV), positive predictive value (PPV), and accuracy. RESULTS: On the scan-based
      analysis, 18F-DOPA PET and CT/MR showed the following rates: sensitivity,
      specificity, NPV, PPV, and accuracy were 100%, 92.3%, 100%, 96%, and 97.3% versus
      91.7%, 61.5%, 80%, 81.5%, and 81.1%, respectively (P = 0.014). Overall 179
      findings were reported at imaging, of which 139 (77.7%) resulted true sites of
      disease at final outcome. On the lesion-based analysis, the 2 imaging modalities
      showed the following sensitivity, specificity, NPV, PPV, and accuracy rates:
      90.6%, 90%, 73.5%, 96.9%, and 90.5% versus 47.5%, 27.5%, 13.1%, 69.5%, and 43% (P
      < 0.00001). CONCLUSIONS: In our study, 18F-DOPA PET/CT results more accurate than
      CT/MR in advanced stage NB therefore should be taken into consideration for the
      diagnostic workup of these patients.

PMID- 22391728
TI  - Successful thrombolysis, early luxury perfusion, and spectacular outcome after
      acute ischemic stroke.

PMID- 22391729
TI  - Intense 18F-fluoride accumulation in liver metastases from a neuroendocrine tumor
      after peptide receptor radionuclide therapy.

PMID- 22391730
TI  - 99mTc-tektrotyd SPECT/MRI in the diagnosis of a gastroenteropancreatic
      neuroendocrine tumor.

PMID- 22391731
TI  - 99mTc ECD and 99mTc TRODAT-1 SPECT in Hashimoto encephalopathy.

PMID- 22391732
TI  - Unusual F-18 choline uptake in penile metastasis from prostate cancer.

PMID- 22391733
TI  - A rare case of synchronous bilateral pulmonary neuroendocrine tumor detected by
      68Ga-DOTANOC PET/CT.

PMID- 22391734
TI  - A dual color fluorescent reporter system for the real time detection of promoter
      activity.
AB  - Understanding the mechanisms controlling transcription of a gene requires the
      identification and characterization of its cis-acting regulatory elements. A
      highly useful approach to the identification and characterization of cis-acting
      elements has been the systematic coupling of genomic fragments to reporter
      constructs, so called "promoter bashing". The expression from such reporters must
      be normalized for differences in transient transfection efficiency between cells
      and replicates. A novel dual color fluorescent reporter system to assay the
      promoter activity of a genomic DNA fragment of interest was established by
      cloning a Discosoma red fluorescent protein gene and a green fluorescent protein
      gene into a single vector, giving a system in which the ratio between red and
      green fluorescence is proportional to promoter activity. This system allows real
      time quantitative monitoring of promoter activity. We validated this approach by
      assaying the cis-acting regulatory potential of the peroxisome proliferators
      activated receptor gamma2 gene.

PMID- 22391735
TI  - Characterization of a recombinant endo-type alginate lyase (Alg7D) from
      Saccharophagus degradans.
AB  - A gene, alg7D, from Saccharophagus degradans, coding for a putative alginate
      lyase belonging to the family of polysaccharide lyase-7, was overexpressed in
      Escherichia coli. The properties of the recombinant Alg7D were characterized. The
      enzyme endolytically depolymerized alginate by beta-elimination into oligo
      alginates with degrees of polymerization of 2-5. Its activity was maximal at 50
      degrees C and pH 7 and was slightly increased in the presence of Na(+). The K(M),
      V(max), k(cat), and k(cat)/K(M) values were: 3 mg ml(-1), 6.2 U mg(-1), 1.9 * 10(
      2) s(-1), and 6.3 * 10(-3) mg(-1 )ml s(-1), respectively.

PMID- 22391736
TI  - Tight controlled expression and secretion of Lactobacillus brevis SlpA in
      Lactococcus lactis.
AB  - Prokaryotes commonly present outer cell wall structures composed of a crystalline
      array of proteinaceous subunits, known as surface layers (S-layers). The ORF
      encoding the S-layer protein (SlpA) of Lactobacillus brevis was cloned into
      Lactococcus lactis under the transcriptional control of the xylose-inducible
      expression system (XIES). SlpA was secreted into the extracellular medium, as
      determined by immunoblotting, and assays on the kinetics of SlpA production
      revealed that repression of the system with glucose did not require the depletion
      of xylose from the medium that allows transitory ORF expression. The successful
      use of XIES to express S-layer proteins in the versatile and generally recognized
      as safe species L. lactis opens new possibilities for an efficient production and
      isolation of SlpA S-layer protein for its various applications in biotechnology
      and importantly as an antigen-carrying vehicle.

PMID- 22391737
TI  - Isolation and functional characterization of a transcription factor VpNAC1 from
      Chinese wild Vitis pseudoreticulata.
AB  - NAC (for NAM, ATAF1, 2, and CUC2) family genes encode plant-specific
      transcription factors that play important roles in plant development regulation
      and in abiotic and biotic stresses. However, the function of NAC genes in
      grapevines is not clear. A novel NAC transcription factor, designated as VpNAC1,
      was isolated from Chinese wild Vitis pseudoreticulata. It belongs to the TERN
      subgroup and is a nuclear-targeting protein and functions as a transcriptional
      activator. Moreover, VpNAC1 was induced by the fungus Erysiphe necator and the
      exogenous hormones, particularly salicylic acid, methyl jasmonate and ethylene.
      Over-expression of VpNAC1 in tobacco plants enhanced their resistance to Erysiphe
      cichoracearum and Phytophthora parasitica var. nicotianae Tucker. These results
      suggest that VpNAC1 acts as a positive regulator in biotic stresses.

PMID- 22391738
TI  - Barramundi (Lates calcarifer) desaturase with Delta6/Delta8 dual activities.
AB  - Barramundi is a commercially farmed fish in Australia. To examine the potential
      for barramundi to metabolise dietary alpha-linolenic acid (ALA, 18:3 n-3), the
      existence of barramundi desaturase enzymes was examined. A putative fatty acid
      Delta6 desaturase was cloned from barramundi liver and expressed in yeast.
      Functional expression revealed Delta6 desaturase activity with both the 18 carbon
      (C(18)) and C(24) n-3 fatty acids, ALA and 24:5 n-3 as well as the C(18) n-6
      fatty, linoleic acid (LA, 18:2 n-6). Metabolism of ALA was favoured over LA. The
      enzyme also had Delta8 desaturase activity which raises the potential for
      synthesis in barramundi of omega-3 (n-3) long chain polyunsaturated fatty acids
      from ALA via a pathway that bypasses the initial Delta6 desaturase step. Our
      findings not only provide molecular evidence for the fatty acid desaturation
      pathway in the barramundi but also highlight the importance of taking
      extracellular fatty acid levels into account when assessing enzyme activity
      expressed in Saccharomyces cerevisiae.

PMID- 22391739
TI  - Congenital smooth muscle hamartoma of the palpebral conjunctiva.
AB  - Smooth muscle hamartoma is defined as a disorganized focus or an overgrowth of
      mature smooth muscle, generally with low capacity of autonomous growth and benign
      behavior. The implicated tissues are mature and proliferate in a disorganized
      fashion. A healthy 5-day-old Mexican boy was referred to the authors' hospital in
      Mexico city for evaluation of a "cystic" lesion of the right eye that had been
      noted since birth. The pregnancy and delivery were unremarkable. On physical
      examination, there was a reddish-pink soft lesion with a tender "cystic"
      appearance, which was probably emerging from the upper eyelid conjunctiva, which
      measured 2.7 cm in its widest diameter and transilluminated. Ultrasound imaging
      revealed an anterior "cystic" lesion with normally formed phakic eye. An
      excisional biopsy was performed, and the lesion was dissected from the upper
      tarsal subconjunctival space. Subsequent histologic and immunohistochemical
      findings were consistent with the diagnosis of congenital smooth muscle hamartoma
      (CSMH) of the tarsal conjunctiva. The authors' research revealed that only one
      case of CSMH localized in the conjunctiva (Roper GJ, Smith MS, Lueder GT.
      Congenital smooth muscle hamartoma of the conjunctival fornix. Am J Ophthalmol.
      1999;128:643-4) has been reported to date in the literature. To the best of the
      authors' knowledge, this current case would be the second case reported of CSMH
      in this anatomic location. Therefore, the authors' recommendation is to include
      CSMH in the differential diagnosis of a cystic mass that presents in the fornix
      and palpebral conjunctiva.

PMID- 22391740
TI  - Does upper lid blepharoplasty improve contrast sensitivity?
AB  - PURPOSE: To assess the effect of upper eyelid blepharoplasty surgery on contrast
      sensitivity. METHODS: A prospective study was performed. Pre- and postoperative
      contrast sensitivity measurements were taken on patients undergoing routine upper
      eyelid blepharoplasty surgery. The patients were selected for surgery on the
      basis of a functional visual field effect from dermatochalasis. Contrast
      sensitivity was measured using a Pelli-Robson chart, read at 1 m under standard
      lighting conditions. This produces a result in log contrast sensitivity. Other
      data collected included visual acuity and an automated 60:4 visual field. A
      paired t test was used to assess the change in contrast sensitivity. RESULTS: 28
      eyes of 14 patients underwent upper eyelid blepharoplasty surgery. The mean
      preoperative log contrast sensitivity was 1.49, and the mean postoperative log
      contrast sensitivity was 1.64. The mean increase in log contrast sensitivity was
      0.14 (range 0-0.45). The increase in log contrast sensitivity was statistically
      significant (p = 0.00002). CONCLUSIONS: Dermatochalasis is well known to cause
      visual field defects in many patients. Anecdotally, patients often report that
      their vision is brighter following upper eyelid blepharoplasty. The authors have
      demonstrated a significant increase in contrast sensitivity in patients who have
      undergone upper eyelid blepharoplasty surgery. This information may be of use in
      justifying blepharoplasty surgery in the future.

PMID- 22391741
TI  - Orbital inflammation after dental procedures.
AB  - This study reports 3 cases of acute orbital inflammation that occurred within 3
      weeks of various dental procedures and offers a possible mechanism as to their
      cause. The charts of 3 patients were retrospectively examined. Clinical notes,
      laboratory testing, and imaging studies were reviewed. The cases involved a 36
      year old woman, a 61-year-old woman, and a 44-year-old woman who developed acute
      dacryoadenitis after tooth extraction in the former case and after routine dental
      cleaning in the latter 2. All cases were initially treated with an oral steroid
      taper over 6 to 8 weeks. The first 2 cases resolved promptly and have remained
      quiescent. The last individual had recurrent symptoms prompting lacrimal gland
      biopsy that demonstrated chronic, nongranulomatous inflammation without
      monoclonality. The patient subsequently responded to periorbital steroid
      injection only to have a recurrent bout of inflammation after repeat dental
      cleaning. Another periorbital steroid injection resulted in resolution of
      inflammation. The authors propose that a subset of acute orbital inflammation may
      represent an autoimmune response triggered by dental manipulation. These cases
      are suggestive of an atypical variant of noninfectious, microbe-induced
      inflammation.

PMID- 22391742
TI  - Multiple intratarsal keratinous cysts of the eyelid.
AB  - Intratarsal keratinous cysts are uncommonly reported entities that originate
      within the tarsal plate. Previously reported cysts have always been solitary,
      whether primary or recurrent. The authors present an unusual case of a 50-year
      old man with 11 intratarsal keratinous cysts on a single eyelid. Complete
      excision of all the cysts was curative for at least 2 months.

PMID- 22391743
TI  - Alteration of some inflammatory biomarkers by dietary oxysterols in rats.
AB  - Oxysterols are structurally similar to cholesterol, but are characterized by one
      or more additional oxygen-containing functional groups. These compounds are
      implicated in inflammation given their ability to cause irreversible damage to
      vascular cells. The aim of this study was to study the alteration of some
      inflammatory biomarkers in Wistar rats in response to dietary oxysterols.
      Eighteen rats were randomly divided into three groups of six rats each. A
      standard diet supplemented with 1% (w/w) pure cholesterol (Chol group) or 1%
      (w/w) of an oxidized cholesterol mixture (COPs group) was fed for 8 weeks. Blood
      serum was separated; abdominal, pericardial, and epididymal adipose tissue was
      removed carefully. The COPs subjects exhibited significant increase in blood
      pressure and serum triacylgycerols as well as increased body fat index and
      pericardic, abdominal, and epididymal adipose tissue. These effects were
      accompanied by elevated circulating levels of plasma high-sensitivity C-reactive
      protein, tumor necrosis factor alpha, and resistin. We suggest that dietary
      oxysterols have an important pro-inflammatory effect.

PMID- 22391744
TI  - Postconditioning with alpha7nAChR agonist attenuates systemic inflammatory
      response to myocardial ischemia--reperfusion injury in rats.
AB  - The inflammatory response plays a major role in ischemia-reperfusion injury
      (IRI). Considering that cholinergic stimulation can inhibit inflammatory response
      through the cholinergic anti-inflammatory pathway (CAP) and the alpha subunit
      containing nicotinic acetylcholine receptor(alpha7nAChR) expressed by immune
      cells is an important component of CAP, we assessed the effect of
      postconditioning with alpha7nAChR agonist on systemic inflammatory response
      during the myocardial ischemia-reperfusion process in an in vivo rat model.
      Thirty Sprague Dawley rats were randomly divided into three groups: sham group,
      control group, and postconditioning with alpha7nAChR agonist group (PP group). In
      the groups other than the sham group, the left anterior descending coronary
      artery was ligated for 30 min followed by a 180-min reperfusion. At the end of
      the experiment, the serum levels of troponin I, tumor necrosis factor alpha,
      interleukin-6, and high-mobility group box 1 were assayed, and the infarct size
      was assessed. The results showed that postconditioning with alpha7nAChR agonist
      significantly attenuated the systemic inflammatory response to myocardial IRI, as
      evidenced by decreased serum levels of tumor necrosis factor alpha and high
      mobility group box 1. Also, this treatment protected against myocardial IRI, as
      shown by reduced infarct size and serum troponin I level.

PMID- 22391745
TI  - Protection against titanium particle-induced inflammatory osteolysis by the
      proteasome inhibitor bortezomib in vivo.
AB  - Wear particle-induced vascularized granulomatous inflammation and subsequent
      inflammatory osteolysis is the most common cause of aseptic loosening after total
      joint replacement (TJR); however, the precise mechanism by which this occurs is
      unclear. This study investigates the effects of the proteasome inhibitor
      bortezomib (Bzb) on the expression of key biochemical markers of bone metabolism
      and vascularised granulomatous tissues, such as receptor activator of nuclear
      factor-kappaB ligand (RANKL), osteoprotegerin (OPG), vascular endothelial growth
      factor (VEGF) and tumor necrosis factor receptor-associated factor 6 (TRAF6). In
      addition, the effect of Bzb on apoptosis of CD68+ cells was examined. A total of
      32 female BALB/C mice were randomly divided into four groups. After implantation
      of calvaria bone from syngeneic littermates, titanium (Ti) particles were
      injected into established air pouches for all mice (excluding negative controls)
      to provoke inflammatory osteolysis. Subsequently, Bzb was administered at a ratio
      of 0, 0.1, or 0.5 mg/kg on day 1, 4, 8, and 11 post-surgery to alleviate this
      response. All of the air pouches were harvested 14 days after the surgical
      procedure and were processed for molecular and histological analysis. The results
      demonstrated that Ti injection elevated the expression of RANKL, OPG, VEGF, and
      TRAF6 at both the gene and protein levels, increased counts of infiltrated cells
      and thickness of air pouch membranes, and elevated the apoptosis index (AI) of
      CD68+ cells. Bzb treatment significantly improved Ti particle-induced implanted
      bone osteolysis, attenuated vascularised granulomatous tissues and elevated AI of
      CD68+ cells. Therefore, the proteasome pathway may represent an effective
      therapeutic target for the prevention and treatment of aseptic loosening.

PMID- 22391746
TI  - Resveratrol Inhibits respiratory syncytial virus-induced IL-6 production,
      decreases viral replication, and downregulates TRIF expression in airway
      epithelial cells.
AB  - Respiratory syncytial virus (RSV) is the most common pathogen responsible for
      lower respiratory diseases in children. So far, there is no effective treatment
      or preventative vaccine available for RSV infection, although ribavirin and
      dexamethasone are commonly prescribed. Resveratrol has been shown to inhibit the
      replication of several other viruses, thus the effect of resveratrol on RSV
      induced inflammatory mediators in 9HTEo cell cultures was evaluated, and possible
      mechanisms of action were explored and compared with dexamethasone and ribavirin.
      Incubation with resveratrol resulted in decreased IL-6 production and partial
      inhibition of RSV replication. Resveratrol treatment also inhibited virus-induced
      TIR-domain-containing adapter-inducing interferon-beta (TRIF) and TANK binding
      kinase 1 (TBK1) protein expression. These data demonstrate the ability of
      resveratrol to inhibit cytokine production by RSV in airway epithelial cells,
      indicating that it might be a therapeutic agent with both anti-inflammatory and
      antiviral potential for the treatment of RSV infection.

PMID- 22391747
TI  - Volunteering and subjective well-being in midlife and older adults: the role of
      supportive social networks.
AB  - OBJECTIVE: This study examined the extent to which associations between
      volunteering and subjective well-being (SWB) could be related to volunteers
      having more supportive social networks relative to nonvolunteers. METHOD: The
      sample consisted of 561 midlife and older adults (aged 55-94 years) from the
      TRAnsitions In Later Life study. Multiple mediation analyses examined
      associations between hours spent volunteering per week; availability of social
      support from friends, relatives, and neighbors; positive and negative social
      exchanges; and SWB. RESULTS: The results indicated that the higher life
      satisfaction and positive affect reported by those who volunteer at moderate
      levels (up to 7 hr per week) are related to their higher levels of positive
      social exchanges and greater availability of social support from friends and
      family, relative to nonvolunteers. Those who volunteer at higher levels (7 hr or
      more per week) also reported greater levels of positive affect in comparison to
      nonvolunteers, and this was related to their greater availability of social
      support from friends. Availability of support from friends accounted for the
      greatest proportion of the volunteering-SWB associations. DISCUSSION: The
      findings suggest that the positive SWB associated with volunteering is related to
      volunteers' more extensive friend and family networks.

PMID- 22391748
TI  - Considering life course concepts.

PMID- 22391750
TI  - A historical cycle control comparison of two drospirenone-containing combined
      oral contraceptives: ethinylestradiol 30 MUg/drospirenone 3 mg administered in a
      21/7 regimen versus ethinylestradiol 20 MUg/drospirenone 3 mg administered in a
      24/4 regimen.
AB  - OBJECTIVES: To compare the bleeding patterns and cycle control of an oral
      contraceptive (OC) containing ethinylestradiol (EE) 30 MUg/drospirenone (drsp)
      3mg administered in a 21/7 regimen versus a lower-dose OC containing EE 20
      MUg/drsp 3mg administered in a 24/4 regimen, using data from two identically
      designed studies. MATERIALS AND METHODS: In the first study, 326 healthy women
      (18-35 years) received EE 30 MUg/drsp 3mg in a 21/7 regimen. In the second study,
      1027 healthy women (17-36 years) received EE 20 MUg/drsp 3mg in a 24/4 regimen.
      Participants recorded bleeding using daily completed diaries over 13 treatment
      cycles. RESULTS: During cycles 1-12, the prevalence of scheduled withdrawal
      bleeding was lower with EE 20 MUg/drsp 3mg 24/4 than with EE 30 MUg/drsp 3mg 21/7
      (82.0-91.7% versus 94.8-100.0% of women, respectively); moreover, a higher
      proportion of women reported a maximum intensity of light scheduled withdrawal
      bleeding with EE 20 MUg/drsp 3mg 24/4 than with EE 30 MUg/drsp 3mg 21/7 (30.9
      39.0% versus 13.8-20.5% of women, respectively). In cycles 2-13, unscheduled
      intracyclic bleeding was reported by 7.7-13.8% of EE 20 MUg/drsp 3mg 24/4
      recipients and 3.8-7.9% of EE 30 MUg/drsp 3mg 21/7 recipients; these were mainly
      single bleeding days. During reference periods 1-4, the mean number of bleeding
      episodes was similar between groups (3.1-3.3 episodes with EE 20 MUg/drsp 3mg
      24/4 versus 3.2 episodes with EE 30 MUg/drsp 3mg 21/7). CONCLUSIONS: A low-dose
      24/4 regimen OC containing EE 20 MUg/drsp 3mg is generally comparable in terms of
      bleeding to a higher-dose 21/7 regimen OC containing EE30 MUg/drsp 3mg. Between
      treatment differences in bleeding intensity and unscheduled intracyclic bleeding
      rates were observed.

PMID- 22391749
TI  - Race/ethnic and nativity disparities in later life physical performance: the role
      of health and socioeconomic status over the life course.
AB  - OBJECTIVES: We examine race/ethnic and nativity differences in objective measures
      of physical performance (i.e., peak expiratory flow, grip strength, and gait
      speed) in a nationally representative sample of older Whites, Blacks, and
      Hispanics. We also examine whether detailed measures of childhood and adult
      health and socioeconomic status (SES) mediate race/ethnic differences in physical
      performance. METHOD: We use data from the Health and Retirement Study, a
      population-based sample of older Americans born before 1947, and 3 measures of
      physical performance. Nested ordinary least squares models examine whether
      childhood and adult health and SES mediate race/ethnic differences in
      performance. RESULTS: We find large and significant race/ethnic and nativity
      differences in lung function, grip strength, and gait speed. Adjusting for
      childhood and current adult health and SES reduces race/ethnic differences in
      physical performance but does not eliminate them entirely. Childhood health and
      SES as well as more proximal levels of SES are important determinants of
      race/ethnic disparities in later life physical performance. DISCUSSION: The
      analysis highlights that a large proportion of race/ethnic and nativity
      disparities result from health and socioeconomic disadvantages in both early life
      and adulthood and thus suggests multiple intervention points at which disparities
      can be reduced.

PMID- 22391751
TI  - Work-related laryngeal syndromes.
AB  - PURPOSE OF REVIEW: This review summarizes recent literature regarding the
      association of nonorganic laryngeal dysfunction with occupational exposures.
      Laryngeal dysfunction may masquerade as asthma and is an important consideration
      in patients with work-associated respiratory symptoms. RECENT FINDINGS: Although
      there is lack of consensus regarding clinical features, vocal cord dysfunction
      (VCD) is the most well appreciated form of nonorganic laryngeal dysfunction.
      There are significant gaps in the literature regarding the occupational
      epidemiology of laryngeal dysfunction, however, occupational exposures such as
      upper airway irritants may be associated with the onset of symptoms. Recurrent
      work-associated laryngeal dysfunction has been described in occupational groups
      including the military and professional athletes. Recent theories have considered
      that VCD may be a state of laryngeal hyperresponsiveness associated with both
      intrinsic and extrinsic factors. SUMMARY: Laryngeal dysfunction is an important
      consideration in patients with work-associated respiratory symptoms. Clinicians
      should have a high index of suspicion, in particular, if symptoms are associated
      with exposure to a respiratory irritant. Situations of high psychological stress
      may also be associated with recurrent symptoms. There is a requirement for
      evidence-based guidelines for the diagnosis and management of laryngeal
      dysfunction, which should also address work-related factors.

PMID- 22391752
TI  - The current diagnostic role of the specific occupational laboratory challenge
      test.
AB  - PURPOSE OF REVIEW: Classically, the specific occupational challenge test has been
      considered as the reference test in the diagnosis of occupational asthma. The
      present study assesses the usefulness of this test for diagnosing this disease
      and compares it with other diagnostic methods. RECENT FINDINGS: Occupational
      asthma is the most frequent work-related respiratory disease in developed
      countries. Its correct diagnosis is vitally important not only from the medical
      point of view, but also in view of the disease's major socio-economic
      repercussions both for the patient and for society as a whole. Diagnosis is based
      on clinical suspicion of bronchial asthma and of a possible association with the
      patient's occupation. Various diagnostic strategies have been proposed, including
      clinical history, immunological test, spirometry, the study of peak flow, the
      methacholine test and the specific occupational challenge test, as well as
      studies of bronchial inflammation using noninvasive methods. SUMMARY: The
      specific occupational challenge test remains the reference test for the diagnosis
      of occupational asthma for causal agents of both high and low molecular weight.

PMID- 22391753
TI  - Allergens and bacteria interaction in the induction of basophil activation:  is
      this the lost ring between allergy and infections in pediatric patients?
AB  - PURPOSE OF REVIEW: The aim of this review is to describe the relationships
      between allergy and infectious diseases, with specific attention on bacterial
      infection. According to the most recent literature, bacteria could be considered
      also as one of the major causes of asthma exacerbations that we need to further
      explore. RECENT FINDINGS: The availability of novel methods to detect large
      panels of pathogens, including viruses and bacteria specific for the upper
      respiratory tract, together with the capacity of evaluating how basophils are
      activated, has changed the point of view of the mechanisms related to asthma
      exacerbations. The recent finding that basophils are activated in the presence of
      suboptimal doses of allergens and bacteria has been recently described and may
      explain the clinical behavior of allergy exacerbation. Indeed the activation of
      basophils induces the secretion of mediators, which, at bronchial level, may
      cause bronchospasm that leads to an asthma exacerbation in patients with
      infection. The contrary is also true. SUMMARY: Although the explanations for
      these facts are numerous, at present, bacteria seem to play a relevant role in
      the worsening of asthma in infected patients.

PMID- 22391754
TI  - Influence of poverty and infection on asthma in Latin America.
AB  - PURPOSE OF REVIEW: Asthma in Latin America is a growing public health problem and
      seems to be most prevalent and cause most morbidity among poor urban populations.
      This article will review the findings of recent human studies of the associations
      of asthma prevalence in Latin America with factors associated with poverty and
      inequality including childhood infections, stress, environment, nutrition and
      diet. RECENT FINDINGS: Most asthma in childhood in Latin America is nonatopic and
      has been associated with exposures related to environmental dirt, diet and
      psychosocial distress. These factors are strongly linked to poverty and
      inequality. Interestingly, infections with bacterial, viral and parasitic
      pathogens in childhood appear to attenuate atopy in childhood but have no effect
      on asthma symptoms. There are biologically plausible mechanisms by which dirt
      exposures (e.g. endotoxin and other microbial products and nonmicrobial
      irritants), diet and obesity and psychosocial stress may cause airways
      inflammation. SUMMARY: Most childhood asthma in Latin America is nonatopic for
      which important risk factors are those of poverty including poor hygiene (i.e.
      dirt), poor diet and obesity and psychosocial stress. There is evidence that
      exposures to infections in early childhood reduce atopy but not asthma. Research
      is needed to identify causes of nonatopic asthma that may be suitable for primary
      prevention or other public health intervention strategies for asthma in Latin
      America.

PMID- 22391755
TI  - Obesity and childhood asthma - mechanisms and manifestations.
AB  - PURPOSE OF REVIEW: Obesity is a chronic condition affecting children worldwide.
      However, the prevalence is higher in asthmatic children. Obese children most
      likely become obese adults. Understanding the clinical presentation of this
      subgroup is essential to their clinical management, now and in the future. This
      review highlights the most recent findings over the past 18 months in
      understanding the presentation and potential mechanisms of obesity in childhood
      asthma. RECENT FINDINGS: Recent research suggests that inhaled corticosteroid
      efficacy is reduced in obese asthmatic children whereas ventilatory function and
      bronchoreactivity appear to be marginally affected. A paucity of studies
      describing airway inflammation and lung volume measurements in this subgroup
      limits their clinical characterization. Recent studies indicate metabolic
      abnormalities that typically manifest with excess adiposity may be associated
      with asthma, providing an interesting factor in the asthma-obesity link. The
      inception, persistence and composition of obesity prove important considerations
      for future studies. SUMMARY: Highlighted is the need for more descriptive airway
      inflammation studies, lung volume assessments and longitudinal studies to better
      characterize the obese asthma phenotype in children and understand the
      pathogenesis from childhood to adulthood. Understanding the manifestations and
      mechanisms of obese asthma in childhood will help direct clinical management and
      targeted therapeutic interventions.

PMID- 22391756
TI  - Prognostic significance of serum antioxidant parameters in immunocompetent
      patients with cryptococcal meningitis.
AB  - The purpose of this investigation was to determine whether endogenous
      antioxidants were prognostic factors in immunocompetent patients with
      cryptococcal meningitis (CM). The clinical features, alterations of serum
      albumin, bilirubin, and uric acid (UA) levels before and after six weeks of
      treatment in 94 immunocompetent patients with CM from January 2000 to December
      2010 were retrospectively analyzed. The patients with CM had lower serum albumin
      and UA levels and higher bilirubin levels before treatment. After six weeks of
      treatment, the serum bilirubin levels decreased significantly and the serum UA
      levels increased significantly in 'cured/improved' patients. The serum UA level
      was negatively correlated with log cerebrospinal fluid (CSF) cryptococcal count
      and positively correlated with the CSF glucose level. A significantly lower level
      of serum UA was associated with high CSF open pressure, hydrocephalus, brain
      lesions, and consciousness disturbance. Moreover, the good outcome was 7.779
      times more likely to occur in patients with an increase in the serum UA level
      >=38.8% after six weeks of treatment. A logistic regression analysis also
      confirmed that an increase in the serum UA level >=38.8% after six weeks of
      treatment was an independent good outcome predictor. Though there were abnormal
      conditions of serum antioxidants, the variation in the UA level could serve as a
      potential indicator of therapeutic efficacy in immunocompetent patients with CM.

PMID- 22391757
TI  - Incidence and management of presumption of Lyme borreliosis in Belgium: recent
      data from the sentinel network of general practitioners.
AB  - An increasing incidence of tick bites and Lyme disease has been noticed
      internationally. The aims of this study are threefold: to estimate the incidence
      of tick bites and erythema migrans, to assess the compliance of the general
      practitioners (GPs) with the recommendations about the management of tick bites
      and erythema migrans, and finally, to have a look at the evolution over time,
      both on incidence and management. We used data of the Belgian network of sentinel
      general practitioners (SGP) to study the incidence rates in Belgium, the trend
      over time, and the degree of compliance of the SGP. The overall Belgian incidence
      rates in the SGP practice in 2008-2009 were 18.65 (95% CI 17.29-20.08) per 10,000
      persons for tick bites and 9.02 (95% CI 8.08-10.03) for erythema migrans. The
      diagnostic management of patients with an asymptomatic tick bite has worsened
      over time, while the therapeutic management of erythema migrans has improved over
      time. The international increasing trend of the incidence was not observed in the
      SGP. There is still room for improvement concerning the approach of the GPs.
      Recommendations could help to improve their approach.

PMID- 22391758
TI  - Prolonged carriage of resistant E. coli by returned travellers: clonality, risk
      factors and bacterial characteristics.
AB  - The aim of this study was to delineate the potential risks and dynamics of the
      prolonged carriage of resistant E. coli in returned travellers. A sample of 274
      previously collected E. coli resistant to ceftriaxone (CRO), ciprofloxacin,
      gentamicin and/or nalidixic acid recovered from 102 travellers was studied.
      Travellers were assessed pre-travel then longitudinally (maximum 6 months) with
      peri-rectal/rectal swabs. Clonality was determined by REP-PCR and the presence of
      O25b-ST131 was assessed. Comparison was made longitudinally for individuals and
      between identified co-travellers. The risk of prolonged carriage was lower for
      CRO than for ciprofloxacin or gentamicin resistance. Repeated isolation of the
      same phenotype at different time points occurred in 19% of initial CRO-resistant
      carriers compared with 50% of ciprofloxacin- or gentamicin-resistant carriers.
      The duration of carriage was also longer for the latter resistance phenotypes
      (75th quartile 8 vs 62 and 63 days respectively). In multivariate analysis, risks
      of prolonged carriage included antimicrobial use whilst travelling (3.3, 1.3-8.4)
      and phylogenetic group B2 (9.3, 3.4-25.6) and D (3.8, 1.6-8.8). Clonality amongst
      longitudinal isolates from the same participant was demonstrated in 92% of
      participants who were assessable and most marked amongst CRO-resistant isolates.
      ST-131 was surprisingly infrequent (3% of participants). Prolonged carriage of
      ciprofloxacin- and gentamicin-resistant isolates is more frequent and prolonged
      than CRO resistance after travel. Risks of prolonged carriage indicate a
      contribution of host and bacterial factors to this carriage. These require
      further elucidation. The strong clonality identified suggests that carriage of a
      "phenotype" was mediated by persistence of bacteria/plasmid combinations rather
      than persistence of the plasmid after horizontal transfer to other bacteria.

PMID- 22391760
TI  - Initial dose of vancomycin based on body weight and creatinine clearance to
      minimize inadequate trough levels in Japanese adults.
AB  - Our aims were to elucidate the factors that affected vancomycin (VCM) serum
      trough levels and to find the optimal initial dose based on creatinine clearance
      (CrCl) and body weight (BW) to minimize inadequate trough levels in a
      retrospective observational study among Japanese adults. One hundred and six
      inpatients, in whom VCM trough levels were measured after completing the third
      dosing, were consecutively recruited into our study in a tertiary hospital. We
      considered the frequency of <30% as low. In the generalized linear model, initial
      VCM total daily dose, CrCl, and BW were independent risk factors of VCM trough
      levels. In patients with CrCl >=30 and <50 mL/min, 1 g/day yielded low
      frequencies of a trough level of >=20 mcg/mL, regardless of BW. In patients with
      CrCl >=50 mL/min, 2 g/day yielded low frequencies of a trough level of <10 mcg/mL
      in patients weighing <55 kg, but not in patients weighing >=55 kg. Optimal VCM
      initial total daily dose may be 1 g/day in patients with CrCl >=30 and <50 mL/min
      regardless of BW and 2 g/day in patients weighing <55 kg with CrCl >=50 mL/min
      among Japanese adults.

PMID- 22391761
TI  - Chiral recognition of carbon nanoforms.
AB  - The selective recognition of chiral carbon nanoforms poses a fundamental
      challenge. New design principles must be devised to construct hosts capable of
      enantiodiscrimination between species in which chirality does not arise from
      asymmetric carbon atoms. In this emerging area article, we provide an overview of
      some of the relatively few successful examples of chiral recognition of carbon
      nanoforms, highlighting their common features with the aim of helping to develop
      general trends for the design of new generations of hosts.

PMID- 22391759
TI  - Milleri group streptococcus--a stepchild in the viridans family.
AB  - The purpose of this investigation was to provide a comprehensive review of the
      pathogenic role and spectrum of disease of milleri group streptococci, with
      special attention to bloodstream invasion and to possible differential roles
      among the three species. All consecutive isolates of milleri group streptococci
      from any anatomic source, during a 37-month period, in a tertiary care teaching
      hospital in Tel-Aviv, Israel, were thoroughly investigated. Identification to the
      species level was performed by an automated system.Streptococcus anginosus
      constituted 82% of the 245 patient-unique isolates from hospitalized patients.
      All nonurinary isolates were involved in pyogenic infections mostly originating
      from the gastrointestinal tract, with bacteremia in 28 cases. The 71 urinary
      isolates represented either urinary tract infection or nonsignificant
      bacteriuria. No specific association could be detected between species and the
      infection site, except for a higher relative representation of Streptococcus
      constellatus in bacteremia. Milleri group streptococci are common in clinical
      practice and play a different pathogenic role to other viridans streptococci. Due
      to their invariable association with pyogenic processes, their presence in blood
      warrants immediate focus identification. In addition, they have a previously
      unappreciated clinical niche concerning urinary tract infection. The
      identification of viridans streptococci to the species level is of paramount
      clinical significance.

PMID- 22391762
TI  - Long-term clinical outcome of patients with recurrent epithelial ovarian
      carcinoma: is it the same for each histological type?
AB  - OBJECTIVE: This study was conducted to estimate the long-term clinical outcome of
      patients with recurrent ovarian carcinoma (ROC). METHODS: Six hundred three
      patients with ROC were analyzed in this study. The pathological slides were
      evaluated under central pathological review. The prognostic significances of
      clinicopathologic factors were evaluated using both univariate and multivariate
      analysis. RESULTS: The 5-year overall survival (OS) and postrecurrence survival
      (PRS) rates were 31.1 and 16.9%, respectively. On stratifying to treatment
      periods, the PRS has been prolonged over the last decade (year >=2000) compared
      with before this period (year <=1999) (P = 0.0002). In contrast, on stratifying
      to histological types and treatment periods, in both OS and PRS, the prognosis of
      patients with the nonmucinous/clear-cell histology, including serous,
      endometrioid, and other histological types, was significantly improved after 2000
      compared with before (year <=1999) (OS, P = 0.0009; PRS, P < 0.0001). In
      contrast, that of patients with the mucinous/clear-cell histology did not
      significantly differ regardless of the treatment period (>=2000 vs <=1999: OS, P
      = 0.3887; PRS, P = 0.7617). In multivariate analysis, the stage, period of
      starting initial treatment, histological type, and the treatment-free interval
      were independent prognostic factors of a poor OS and PRS (OS/PRS: histological
      type: mucinous/clear-cell vs nonmucinous/clear-cell: hazard ratio, 1.300/1.498;
      95% confidence interval [CI], 1.039-1.626/1.197-1.874). CONCLUSIONS: Despite the
      continuous administration of treatment for ROC, survival is poor, and the extent
      of therapeutic progress differs according to the histological type.

PMID- 22391763
TI  - HLA class II DRB1*1302 allele protects against progression to cervical
      intraepithelial neoplasia grade 3: a multicenter prospective cohort study.
AB  - OBJECTIVE: Genetic variations in human leukocyte antigens (HLA) class II regions
      may influence the risk of cervical cancer by altering the efficiency of the
      immune responses to human papillomavirus antigens. This prospective study was
      designed to evaluate the effects of HLA class II alleles on the natural course of
      cervical precursor lesions. METHODS: We followed a total of 454 Japanese women
      with cytological low-grade squamous intraepithelial lesion (LSIL) and
      histological cervical intraepithelial neoplasia grades 1 to 2 (CIN1-CIN2).
      Patients were tested for HLA class II alleles and cervical human papillomavirus
      DNA at the time of entry and then monitored by cytology and colposcopy every 4
      months for a mean follow-up of 39.0 months. We analyzed cumulative probabilities
      of cytological regression to at least 2 consecutive negative Papanicolaou tests
      and histological progression to biopsy-positive CIN3. RESULTS: During the follow
      up period, 39 lesions progressed to CIN3, and 282 lesions regressed to normal
      cytology. Progression to CIN3 did not occur in DRB1*1302-positive women, and this
      protective effect of DRB1*1302 was statistically significant (P = 0.03). Low
      grade squamous intraepithelial lesion regressed to normal cytology more quickly
      in DRB1*1302-positive women than in DRB1*1302-negative women (median time, 8.9
      months vs 14.2 months), although the difference was not statistically significant
      (P = 0.16). The risk of LSIL persistence or progression to CIN3 within 5 years
      was not affected by any other HLA class II alleles. CONCLUSION: By using a
      prospective study design, we demonstrated the protective effect of the DRB1*1302
      allele against progression to CIN3 among Japanese women with LSIL.

PMID- 22391764
TI  - Structure-function relationship in the sinus and atrioventricular nodes.
AB  - Recently published optical mapping studies of larger mammals, including humans,
      have identified functionally discrete sinoatrial exit pathways of activation.
      This is in line with earlier mapping studies of the dog and the human but in
      contrast with findings in the mouse and the rabbit, wherein a propagation wave
      front pattern of activation has been described. It underpins the complex three
      dimensional (3D) organization of the cardiac pacemaking and conduction system in
      larger species, wherein sinoatrial and atrioventricular nodal physiologies both
      demonstrate identifiable activation pathways, which coincide with anatomic
      landmarks and histologic architecture, so that in addition to muscle fiber
      orientation and cell coupling, these intrinsic factors act to determine
      excitation pathways. This complex 3D organization increases the effect of source
      to-sink mismatch both by greater variability in the space constant of tissue and
      by the 3D projection of this effect in all directions. Mathematical modeling
      provides a means to study these interactions, and newer models should incorporate
      these additional factors and their effect into the 3D structure of large mammal
      physiology.

PMID- 22391765
TI  - Rupture of a submitral aneurysm into the left atrium.
AB  - Submitral aneurysm is a rare cause of mitral regurgitation. This report describes
      a young boy with this entity, further complicated by its rupture into the left
      atrium.

PMID- 22391766
TI  - An unusual presentation of necrotizing enterocolitis on an echocardiogram.
AB  - This report describes the spontaneous intracardiac air contrast found on the
      echocardiogram of a 5 day-old term neonate with Down syndrome and a complete
      atrioventricular septal defect who had experienced sudden-onset tachypnea and
      systemic desaturation. The stream of air contrast was tracked coming from the
      hepatic veins, and a diagnosis of necrotizing enterocolitis was suspected. An
      abdominal radiograph and ultrasound confirmed the diagnosis.

PMID- 22391767
TI  - Transcatheter closure of a large left atrial aneurysm with a right pulmonary
      artery-to-left atrium connection using the Amplatzer ventricular septal occluder.
AB  - A right pulmonary artery-to-left atrium connection is a very rare cyanotic
      congenital heart defect. Although it is generally treated with surgery, we
      describe the case of a 5-year-old girl whose connection was successfully closed
      the Amplatzer muscular ventricular septal defect occluder. The patient was
      asymptomatic at last follow-up.

PMID- 22391768
TI  - Atrioventricular canal defect as a sign of laterality defect in Ellis-van Creveld
      and polydactyly syndromes with ciliary and Hedgehog signaling dysfunction.

PMID- 22391769
TI  - The influence of metabolic syndrome, physical activity and genotype on catechol-O
      methyl transferase promoter-region methylation in schizophrenia.
AB  - The catechol-O-methyl transferase (COMT) 158Val/Met variant has been suggested to
      play a role in COMT function. Epigenetic regulation of COMT may further influence
      the prevalence of metabolic syndrome in these patient populations. This study
      examined the correlation between COMT promoter methylation and metabolic syndrome
      in schizophrenia patients receiving atypical antipsychotic (AAP) therapy. DNA was
      extracted from peripheral blood samples of schizophrenia subjects screened for
      metabolic syndrome. Pyrosequencing was used to analyze two methylation sites of
      the soluble COMT (COMT-s) promoter region. Associations between AAP use,
      lifestyle variables, metabolic syndrome and COMT genotype with peak methylation
      values were analyzed. Data are reported in 85 subjects. Methylation on CpG site 1
      had a mean of 79.08% (+/-4.71) and it was 12.43% (+/-1.19) on site 2. COMT
      genotype proved to be an indicator of COMT methylation status on site 1 (F(2,
      84)=5.78, P=0.0044) and site 2 (F(2, 84),=3.79, P=0.027). A significant negative
      correlation between physical activity and COMT promoter region methylation was
      found in Val/Val homozygous patients (site 1: P=0.013 and site 2: P=0.019). Those
      homozygous for Met/Met showed a positive correlation between promoter site
      methylation and physical activity (site 1: P=0.027, site 2: P=0.005), and between
      CpG site methylation and metabolic syndrome (site 1: P=0.002; site 2: P=0.001).
      The results of this study suggest that COMT promoter region methylation is
      largely influenced by COMT genotype and that physical activity plays a
      significant role in epigenetic modulation of COMT.

PMID- 22391771
TI  - Intraoperative template-molded bone flap reconstruction for patient-specific
      cranioplasty.
AB  - Cranioplasty is a common neurosurgical procedure. Free-hand molding of polymethyl
      methacrylate (PMMA) cement into complex three-dimensional shapes is often time
      consuming and may result in disappointing cosmetic outcomes. Computer-assisted
      patient-specific implants address these disadvantages but are associated with
      long production times and high costs. In this study, we evaluated the clinical,
      radiological, and cosmetic outcomes of a time-saving and inexpensive
      intraoperative method to mold custom-made implants for immediate single-stage or
      delayed cranioplasty. Data were collected from patients in whom cranioplasty
      became necessary after removal of bone flaps affected by intracranial infection,
      tumor invasion, or trauma. A PMMA replica was cast between a negative form of the
      patient's own bone flap and the original bone flap with exactly the same shape,
      thickness, and dimensions. Clinical and radiological follow-up was performed 2
      months post-surgery. Patient satisfaction (Odom criteria) and cosmesis (visual
      analogue scale for cosmesis) were evaluated 1 to 3 years after cranioplasty.
      Twenty-seven patients underwent intraoperative template-molded patient-specific
      cranioplasty with PMMA. The indications for cranioplasty included bone flap
      infection (56%, n = 15), calvarian tumor resection (37%, n = 10), and defect
      after trauma (7%, n = 2). The mean duration of the molding procedure was 19 +/- 7
      min. Excellent radiological implant alignment was achieved in 94% of the cases.
      All (n = 23) but one patient rated the cosmetic outcome (mean 1.4 years after
      cranioplasty) as excellent (70%, n = 16) or good (26%, n = 6). Intraoperative
      cast-molded reconstructive cranioplasty is a feasible, accurate, fast, and cost
      efficient technique that results in excellent cosmetic outcomes, even with large
      and complex skull defects.

PMID- 22391772
TI  - Whole-body computerized tomography and concomitant spine and head injuries: a
      study of 355 cases.
AB  - The authors present a prospective study on the coexistence of spinal injury (SI)
      and severe traumatic brain injury (TBI) in patients who were involved in traffic
      accidents and arrived at the Emergency Department of Hospital das Clinicas of the
      University of Sao Paulo between September 1, 2003 and December 31, 2009. A whole
      body computed tomography was the diagnostic method employed in all cases. Both
      lesions were observed simultaneously in 69 cases (19.4%), predominantly in males
      (57 individuals, 82.6%). Cranial injuries included epidural hematoma, acute
      subdural hematoma, brain contusion, ventricular hemorrhage and traumatic
      subarachnoid hemorrhage. The transverse processes were the most fragile portion
      of the vertebrae and were more susceptible to fractures. The seventh cervical
      vertebra was the most commonly affected segment, with 24 cases (34.78%). The
      distribution of fractures was similar among the other cervical vertebrae, the
      first four thoracic vertebrae and the lumbar spine. Neurological deficit
      secondary to SI was detected in eight individuals (11.59%) and two individuals
      (2.89%) died. Traumatic subarachnoid hemorrhage was the most common intracranial
      finding (82.6%). Spinal surgery was necessary in 24 patients (34.78%) and brain
      surgery in 18 (26%). Four patients (5.79%) underwent cranial and spinal
      surgeries. The authors conclude that it is necessary a judicious assessment of
      the entire spine of individuals who presented in coma after suffering a brain
      injury associated to multisystemic trauma and whole-body CT scan may play a major
      role in this scenario.

PMID- 22391774
TI  - Is the positive illusory bias illusory? Examining discrepant self-perceptions of
      competence in girls with ADHD.
AB  - It has been claimed that excessively positive self-perceptions of competence are
      a key risk factor for concurrent and subsequent impairments in youth with
      attention-deficit/ hyperactivity disorder (ADHD). We examined whether girls with
      ADHD demonstrate positive illusory self-perceptions in scholastic competence,
      social acceptance, and behavioral conduct domains. We then tested, across a five
      year longitudinal span, whether (a) such self-perceptions versus (b) the
      constituent informant ratings or test scores were more strongly predictive of
      adolescent impairment and positive adjustment. Participants included an
      ethnically diverse sample of 140 girls with ADHD and 88 comparison girls, aged 6
      12 at baseline (M = 9.0, SD = 1.7). Girls with ADHD rated themselves as more
      positive than indicated by external ratings, but these self-reports were still in
      a negative direction (comparison girls rated themselves as less positive than
      these indicators). ADHD subtypes were not related to discrepancy scores. Higher
      rates of depression symptoms were associated with attenuated discrepancy scores.
      Crucially, measures of actual competence were more strongly associated with
      adolescent impairment and positive adjustment than were "illusory" self
      perceptions for girls with ADHD. Our findings challenge the view that, at least
      in girls with ADHD, overly positive and "illusory" appraisals of competence are
      strongly associated with future impairment and adjustment. The key psychometric
      point is that, in difference or discrepancy scores, the individual components of
      such scores should be separately examined.

PMID- 22391775
TI  - Bullying and PTSD symptoms.
AB  - PTSD symptoms related to school bullying have rarely been investigated, and never
      in national samples. We used data from a national survey to investigate this
      among students from grades 8 and 9 (n = 963). The prevalence estimates of
      exposure to bullying were within the range of earlier research findings.
      Multinomial logistic regression showed that boys were 2.27 times more likely to
      be exposed to frequent bullying than girls. A latent variable second-order model
      demonstrated an association between frequency of bullying exposure and PTSD
      symptoms (beta = 0.49). This relationship was not moderated by gender. However,
      the average levels of PTSD symptoms as well as clinical range symptoms were
      higher for girls. For all bullied students, 27.6% of the boys and 40.5% of the
      girls had scores within the clinical range. A mimic model showed that youth who
      identify as being both a bully and a victim of bullying were more troubled than
      those who were victims only. Our findings support the idea that exposure to
      bullying is a potential risk factor for PTSD symptoms among students. Future
      research could investigate whether the same holds for PTSD through diagnostic
      procedures, but this will depend on whether or not bullying is decided to comply
      with the DSM-IV classification of trauma required for diagnosis. Results are
      discussed with regard to their implications for school interventions.

PMID- 22391780
TI  - Dialogues, dilemmas, and disclosures: genomic research and incidental findings.

PMID- 22391776
TI  - Surgical management of proximal bile duct cancers.
AB  - INTRODUCTION: Tumors arising from the proximal biliary tree remain particularly
      challenging with respect to their evaluation and treatment. Complete resection
      with negative histologic margins is the most effective treatment modality.
      RESULTS: However, the majority of patients are not candidates for surgery. Over
      the last decades, advances have evolved to improve resectability and morbidity
      after major liver and bile duct resection. However, these disease processes still
      pose a management challenge. Herein, we provide an overview of proximal bile duct
      cancers, hilar cholangiocarcinoma (HCCa) and intrahepatic cholangiocarcinoma
      (ICCa).

PMID- 22391781
TI  - Resources available for informed prenatal decisions.

PMID- 22391777
TI  - Preneoplastic conditions underlying bile duct cancer.
AB  - BACKGROUND: Malignancies arising from the biliary tract can arise from the
      epithelial lining of the biliary tract and surrounding tissues. Conditions that
      predispose to malignancy as well as preneoplastic changes in biliary tract
      epithelia have been identified. In this overview, we discuss preneoplastic
      conditions of the biliary tract and emphasize their clinical relevance. RESULTS:
      Chronic biliary tract inflammation predisposes to cancer in the biliary tract.
      Biliary tract carcinogenesis involves a multistep process as a consequence of
      chronic biliary epithelial injury or inflammation. Reminiscent of other
      gastrointestinal epithelial malignancies such as gastric, colon, and pancreatic
      cancer, biliary tract cancers may evolve via multistep progression from
      epithelial hyperplasia and dysplasia to malignant transformation. The potential
      role of initiating cells is also becoming recognized. CONCLUSIONS: In spite of
      improved risk factor recognition, and advances in diagnostic tools, the early
      diagnosis of pre-malignant or malignant biliary tract conditions is extremely
      challenging, and there is a paucity of evidence on which to base their
      management. As a result, the role of pre-emptive surgery remains largely
      undefined.

PMID- 22391782
TI  - Medical genetics and genomics curricula focused on the laboratory specialties.

PMID- 22391783
TI  - Fragile X population carrier screening.

PMID- 22391787
TI  - Reaction of facial soft tissues to treatment with a Herbst appliance.
AB  - OBJECTIVE: The objective of this prospective longitudinal study was to
      investigate the reaction of facial soft tissues to treatment with a Herbst
      appliance. We aimed to quantify three-dimensionally (3D) the isolated effect of
      the Herbst appliance and volume changes in the lip profile. PATIENTS AND METHODS:
      The 3D data of the facial soft tissues of 34 patients with skeletal Class II (17
      female and 17 male, mean age 13.5 +/- 1.8 years) were prepared in a standardized
      manner immediately before (T1) and after (T2) treatment with a Herbst appliance.
      Anthropometric evaluation was carried out in sagittal and vertical dimensions. To
      quantify volume changes, pretherapeutic and posttherapeutic images were
      superimposed three-dimensionally and the difference volumes calculated. Following
      testing for normal distribution, a statistical analysis was carried out using the
      paired t test. RESULTS: We observed ventral development of the soft tissues of
      the lower jaw with flattening of the profile curvature and anterior displacement
      of the sublabial region in a total of 27 patients. Anterior facial height was
      lengthened and the facial depth at the lower jaw increased. The largest
      percentage changes were noted in the lip profile, with a reduction in the red
      margin of the upper lip and an increase in lower lip height. We also observed a
      reduction of the sublabial fold in conjunction with a simultaneous increase in
      volume. CONCLUSION: The influence of the Herbst appliance on the facial soft
      tissues is expected to result in a positive treatment outcome, particularly in
      patients with a convex profile, a retrusive lower lip, and a marked sublabial
      fold. We observed a broad clinical spectrum of individual reactions in the facial
      soft tissues. It is, thus, not possible to detect a linear relationship between
      the Herbst treatment and soft tissue changes, making soft tissue changes
      difficult to predict.

PMID- 22391786
TI  - Effectiveness of bionator therapy for Class II malocclusions: a comparative long
      term study.
AB  - OBJECTIVE: The goal of this retrospective study was to examine the effectiveness
      of isolated bionator therapy in Class II patients both longitudinally and over
      the long term. We aimed to determine whether skeletal and/or dentoalveolar
      reactions differ in relationship to the Angle Class (II, Division 1 vs. II,
      Division 2). PATIENTS AND METHODS: A total of 50 juvenile patients with Class II
      malocclusion (? n = 26, ? n = 24) were included. A total of 24 patients presented
      an Angle Class II, Division 1 and 26 an Angle Class II, Division 2. We compared
      the patients' lateral cephalograms taken at the beginning of treatment (t1: 10.1
      years), after active therapy (t2: 13.8 years), and at the end of retention (t3:
      16.4 years) analyzing the following cephalometric parameters: SNA, SNB, ANB,
      ANB(ind), SNPog, Wits appraisal, U1-SN, U1-SpP, L1-MeGo, interincisal angle. Mean
      and standard deviations of each of the variables were calculated. Differences
      between t1-t2 and t2-t3 were tested for statistical significance. Changes in the
      variables were then analyzed biometrically for specific differences in terms of
      Angle Class (II, Division 1 vs. II, Division 2). RESULTS: Between t1 and t2, SNB
      (p = 0.000) and SNPog (p = 0.000) increased significantly, as did ANB (p =
      0.000), while the difference between ANB and ANB(ind) (p = 0.000) and Wits
      appraisal (p = 0.000) decreased significantly. The dentoalveolar variables U1-SN,
      U1-SpP, and the interincisal angle changed significantly in both groups. The
      inclination of the upper incisors was corrected by retrusion in the Class II,
      Division 1 and by protrusion in the Class II, Division 2 group. Only marginal
      changes in all variables between t2 and t3 were observed. CONCLUSION: A
      significant skeletal effect (even in long-time stability) through bionator
      treatment could be confirmed in this study of Class II, Divisions 1 and 2
      patients. The desired effect on the upper front teeth was realized, and there was
      no appreciable dentoalveolar compensation in the mandible.

PMID- 22391788
TI  - Design and characterization of novel peptide-coated lipid nanoparticles for
      targeting anti-HIV drug to CD4 expressing cells.
AB  - Human immunodeficiency virus (HIV) persists in lymph nodes and lymphoid tissues
      even during aggressive drug treatment, likely due to insufficient drug
      concentrations at this site. Therefore, to eliminate this residual virus, methods
      that enhance lymph node drug concentrations are currently being evaluated.
      Although enhanced drug concentrations in tissue have been achieved with drug
      associated lipid nanoparticles, targeting these particles to CD4(+) cells may
      provide specific delivery of drug to HIV target cells and further enhance drug
      efficacy. We have evaluated four candidate peptides with reported binding
      specificity to CD4 for anchoring on lipid nanoparticle preparations previously
      shown to localize in lymph nodes. Terminal cysteine containing candidate peptides
      were conjugated to lipid nanoparticles through maleimide-linked phospholipids for
      targeting to CD4 cells. Using fluorescently labeled lipid nanoparticle binding to
      cells with varying degree of CD4 expression (CEMx174, Molt-4, Jurkat, and Ramos),
      we indentified two peptide sequences that provided CD4 selectivity to
      nanoparticles. These two peptide candidates on lipid nanoparticles bound to cells
      corresponding to the degree of CD4 expression and in a peptide dose dependent
      manner. Further, binding of these targeted lipid nanoparticles was CD4 specific,
      as pre-exposure of CD4(+) cells to anti-CD4 antibodies or free peptides inhibited
      the binding interactions. These results indicate targeting of lipid nanoparticles
      for specific binding to CD4 can be accomplished by tagging CD4 binding peptides
      with peptides, and these results provide a basis for further evaluation of this
      targeted delivery system to enhance antiviral drug delivery to CD4(+) HIV host
      cells, particularly those in lymph nodes and lymphoid tissues.

PMID- 22391789
TI  - Issues and challenges of subvisible and submicron particulate analysis in protein
      solutions.
AB  - The analysis of particulates has been a longstanding challenge in
      biopharmaceutical drug product development and quality control because the active
      constituents themselves may form particulate matter as a degradation product that
      may be difficult to quantify. These analytical challenges were met with success
      as long as the definition of particulate matter remained well within the
      capabilities of the instruments and methods used to measure it. The current
      testing as per USP <788> for parenterals at <=100 mL stipulates that the sample
      "passes" the test if the average number of particles present does not exceed
      6,000 per container at >=10 MUm and does not exceed 600 per container at >=25
      MUm. The new challenge, posed by regulatory direction and academic research, is
      to count and to characterize subvisible particulates that are <=10 MUm with the
      goal of providing higher resolution information about the particulate levels and
      potential consequences of this product quality attribute in vivo. The present
      discussion focuses on two parallel efforts: (a) to develop a model system for
      protein subvisible particulates in samples with high protein concentrations and
      (b) to evaluate the capabilities and limitations of different technologies
      available (at the time these studies were conducted) for subvisible and submicron
      particle (<1 MUm in diameter) sizing and counting. Our findings illustrate the
      importance of using appropriate instrumentation that is adapted to the
      characteristics of the samples to be analyzed. Any sample manipulation to meet
      the capabilities and to accommodate the limitations of the analytical technique
      should be carefully evaluated.

PMID- 22391790
TI  - The solubility-permeability interplay and its implications in formulation design
      and development for poorly soluble drugs.
AB  - While each of the two key parameters of oral drug absorption, the solubility and
      the permeability, has been comprehensively studied separately, the relationship
      and interplay between the two have been largely ignored. For instance, when
      formulating a low-solubility drug using various solubilization techniques: what
      are we doing to the apparent permeability when we increase the solubility?
      Permeability is equal to the drug's diffusion coefficient through the membrane
      times the membrane/aqueous partition coefficient divided by the membrane
      thickness. The direct correlation between the intestinal permeability and the
      membrane/aqueous partitioning, which in turn is dependent on the drug's apparent
      solubility in the GI milieu, suggests that the solubility and the permeability
      are closely associated, exhibiting a certain interplay between them, and the
      current view of treating the one irrespectively of the other may not be
      sufficient. In this paper, we describe the research that has been done thus far,
      and present new data, to shed light on this solubility-permeability interplay. It
      has been shown that decreased apparent permeability accompanies the solubility
      increase when using different solubilization methods. Overall, the weight of the
      evidence indicates that the solubility-permeability interplay cannot be ignored
      when using solubility-enabling formulations; looking solely at the solubility
      enhancement that the formulation enables may be misleading with regards to
      predicting the resulting absorption, and hence, the solubility-permeability
      interplay must be taken into account to strike the optimal solubility
      permeability balance, in order to maximize the overall absorption.

PMID- 22391792
TI  - Proteomic study of the yeast Rhodotorula mucilaginosa RCL-11 under copper stress.
AB  - In order to understand the mechanism involved in Rhodotorula mucilaginosa RCL-11
      resistance to copper a proteomic study was conducted. Atomic absorption
      spectroscopy showed that the copper concentration in the medium decreased from
      0.5 to 0.19 mM 48 h after inoculation of the yeast. Analysis of one-dimensional
      gel electrophoresis of crude cell extracts revealed expression of differential
      bands between cells with and without copper. In order to study this difference,
      two-dimensional electrophoresis of R. mucilaginosa RCL-11 exposed to Cu for 16,
      24, and 48 h was carried out. Identification of differentially expressed proteins
      was performed by MALDI-TOF/TOF. Ten of the 16 spots identified belonged to heat
      shock proteins. Superoxide dismutase, methionine synthase and beta-glucosidase
      were also found over-expressed at high copper concentrations. The results
      obtained in the present work show that when R. mucilaginosa RCL-11 is exposed to
      0.5 mM copper, differential proteins, involved in cell resistance mechanisms, are
      expressed.

PMID- 22391791
TI  - Pharmacokinetics, lymph node uptake, and mechanistic PK model of near-infrared
      dye-labeled bevacizumab after IV and SC administration in mice.
AB  - Our objective was to determine the pharmacokinetics, bioavailability and lymph
      node uptake of the monoclonal antibody bevacizumab, labeled with the near
      infrared (IR) dye 800CW, after intravenous (IV) and subcutaneous (SC)
      administration in mice. Fluorescence imaging and enzyme-linked immunosorbent
      assay (ELISA) assays were developed and validated to measure the concentration of
      bevacizumab in plasma. The bevacizumab-IRDye conjugate remained predominantly
      intact in plasma and in lymph node homogenate samples over a 24-h period, as
      determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and size
      exclusion chromatography. The plasma concentration vs. time plots obtained by
      fluorescence and ELISA measurements were similar; however, unlike ELISA,
      fluorescent imaging was only able to quantitate concentrations for 24 h after
      administration. At a low dose of 0.45 mg/kg, the plasma clearance of bevacizumab
      was 6.96 mL/h/kg after IV administration; this clearance is higher than that
      reported after higher doses. Half-lives of bevacizumab after SC and IV
      administration were 4.6 and 3.9 days, respectively. After SC administration,
      bevacizumab-IRDye800CW was present in the axillary lymph nodes that drain the SC
      site; lymph node uptake of bevacizumab-IRDye 800CW was negligible after IV
      administration. Bevacizumab exhibited complete bioavailability after SC
      administration. Using a compartmental pharmacokinetic model, the fraction
      absorbed through the lymphatics after SC administration was estimated to be about
      1%. This is the first report evaluating the use of fluorescent imaging to
      determine the pharmacokinetics, lymphatic uptake, and bioavailability of a near
      infrared dye-labeled antibody conjugate.

PMID- 22391793
TI  - The protective effects of riluzole on manganese-induced disruption of glutamate
      transporters and glutamine synthetase in the cultured astrocytes.
AB  - Chronic exposure to excessive manganese (Mn) can lead to manganism, a type of
      neurotoxicity accomplished with extracellular glutamate (Glu) accumulation. To
      investigate this accumulation, this study focused on the role of astrocyte
      glutamate transporters (GluTs) and glutamine synthetase (GS), which have roles in
      Glu transport and metabolism, respectively. And the possible protective effects
      of riluzole (a glutamatergic modulator) were studied in relation to Mn exposure.
      At first, the astrocytes were exposed to 0, 125, 250, and 500 MUM MnCl(2) for 24
      h, and 100 MUM riluzole was pretreated to astrocytes for 6 h before 500 MUM
      MnCl(2) exposure. Then, [(3)H]-glutamate uptake was measured by liquid
      scintillation counting; Na(+)-K(+) ATPase and GS activities were determined by a
      colorimetric method; glutamate/aspartate transporter (GLAST), glutamate
      transporter-1 (GLT-1), and GS mRNA expression were determined by RT-PCR and
      protein levels were measured by western blotting. The results showed that Mn
      inhibited Glu uptake, Na(+)-K(+) ATPase and GS activities, GLAST, GLT-1, and GS
      mRNA, and protein in a concentration-dependent manner. And they were
      significantly higher for astrocytes pretreated with 100 MUM riluzole than the
      group exposed to 500 MUM MnCl(2). The results suggested that Mn disrupted Glu
      transport and metabolism by inhibiting GluTs and GS. Riluzole activated
      protective effects on enhancing GluTs and GS to reverse Glu accumulation. In
      conclusion, Mn exposure results in the disruption of GLAST, GLT-1, and GS
      expression and function. Furthermore, riluzole attenuates this Mn toxicity.

PMID- 22391794
TI  - Amounts of Sr and Ca eluted from deciduous enamel to artificial saliva related to
      dental caries.
AB  - This study was performed to elucidate the relationship between dental caries and
      the levels of Sr and Ca eluted from enamel, and to examine whether these elements
      are useful as factors to assess caries risk. The available 103 (Sr) and 108 (Ca)
      samples were obtained among 111 collected deciduous teeth. The healthy regions of
      enamel were decalcified in artificial saliva at pH 6.2 and 5.5. The eluted levels
      of these elements from enamel were determined using atomic absorption
      spectrophotometry. Sr and Ca levels were not affected by the sex nor tooth type.
      Sr levels of the caries-experienced tooth (CE) group were 2.6-fold (pH 6.2) and
      2.2-fold (pH 5.5) higher than those of the sound tooth (ST) group, respectively.
      Furthermore, the Sr levels were significantly higher in the teeth with treated
      than in those with untreated caries. Only at pH 6.2 was a significant difference
      found in Ca levels between the ST and CE groups. In the ST group, at pH 5.5, both
      the Sr and Ca levels significantly increased when the children had six or more
      carious teeth. The Sr and Ca elution levels were significantly inhibited in the
      teeth receiving fluoride application every 3 or 4 months compared to those that
      were not. These findings indicate that Sr can be an indicator of the acid
      resistance of teeth, and a useful factor to assess future caries risk.

PMID- 22391795
TI  - Influence of cadmium exposure on growth and fecundity of freshwater mosquitofish
      Gambusia affinis: in situ and in vivo studies.
AB  - This study aims to investigate the effect of cadmium (Cd) exposure on growth and
      fecundity of mosquitofish Gambusia affinis. For this purpose, two natural
      populations of pregnant females of G. affinis captured from two sites were
      differently contaminated with Cd (S1 present Cd levels 5-fold higher than S2) and
      a sublethal exposure to 0.4 mg CdCl(2)/L (10% of LC(50)) during 56 days was
      conducted in vivo. The length-weight regression revealed a significant difference
      in the growth between these two populations. A significant difference in
      fecundity was also noted between the two populations. Indeed, the embryo numbers
      in pregnant females captured from S1 are significantly higher than those noted in
      pregnant females from S2 (21.17+/-5 and 7.97+/-2.12, respectively; p<0.05).
      Following Cd exposure, we noted a growth perturbation resulting in lower values
      of both indices BWG and SGR following 7 and 21 days (-5.21 and -1.18 for BWG, and
      -2.09 and -0.46 for SGR, respectively) and a recuperation of growing weight at 42
      and 56 days (1.32 and 1.71 for BWG, and 0.45 and 0.54 for SGR, respectively). For
      CF index, we observed a significant difference (p<0.05) between control and Cd
      groups at 7 and 21 days of exposure, and at 21 and 56 days respectively for HSI
      and GSI indices. Furthermore, Cd contents in both tissues (liver and yolk sac)
      and fractions (cytosolic and membrane) are significantly different between groups
      during experimentation. In addition, the Cd contents noticed in the liver
      membrane fraction are significantly higher than those noted in the yolk sac
      tissue. The MTs levels revealed a significant difference between the control and
      Cd groups. In liver tissue, a significant difference was noted, in MTs levels,
      during the Cd exposure (7, 21, 42, and 56 days) while in the yolk sac tissue the
      difference was noted at 42 days of exposure. Taken together, these results imply
      the potential negative effect of Cd on physiological status of G. affinis as
      evidenced by decreasing growth and fecundity rate.

PMID- 22391796
TI  - Monocarboxylate transporters are not responsible for Cr(3+) transport from
      endosomes.
AB  - Cr(3+), similar to Fe(3+), is transported into cells primarily via endocytosis as
      the metal-transferrin complex. As Cr(3+) ions are not readily reduced under
      biological conditions, the ion cannot be transported from endosomes by the same
      mechanism as iron that utilized divalent metal ion transporters. Cr(3+) has been
      hypothesized to potentially be transported as small ligand complexes with a free
      carboxylate functionality by monocarboxylate transporters (MCT), in a similar
      fashion to that proposed for Al(3+). Consequently, mouse C2C12 muscle cells were
      utilized to determine if Cr(3+) is potentially transported by MCT by examining
      the effects of MCT inhibitors on Cr and Fe transport and subcellular distribution
      when the metals are added as their transferrin complexes. The results suggest
      that Cr is not primarily transported by MCT from the endosomes to the cytosol,
      and that another mechanism for this transport needs to be identified.

PMID- 22391797
TI  - Microbial and geochemical assessment of bauxitic un-mined and post-mined
      chronosequence soils from Mocho Mountains, Jamaica.
AB  - Microorganisms are very sensitive to environmental change and can be used to
      gauge anthropogenic impacts and even predict restoration success of degraded
      environments. Here, we report assessment of bauxite mining activities on soil
      biogeochemistry and microbial community structure using un-mined and three post
      mined sites in Jamaica. The post-mined soils represent a chronosequence,
      undergoing restoration since 1987, 1997, and 2007. Soils were collected during
      dry and wet seasons and analyzed for pH, organic matter (OM), total carbon (TC),
      nitrogen (TN), and phosphorus. The microbial community structure was assessed
      through quantitative PCR and massively parallel bacterial ribosomal RNA (rRNA)
      gene sequencing. Edaphic factors and microbial community composition were
      analyzed using multivariate statistical approaches and revealed a significant,
      negative impact of mining on soil that persisted even after greater than 20 years
      of restoration. Seasonal fluctuations contributed to variation in measured soil
      properties and community composition, but they were minor in comparison to long
      term effects of mining. In both seasons, post-mined soils were higher in pH but
      OM, TC, and TN decreased. Bacterial rRNA gene analyses demonstrated a general
      decrease in diversity in post-mined soils and up to a 3-log decrease in rRNA gene
      abundance. Community composition analyses demonstrated that bacteria from the
      Proteobacteria (alpha, beta, gamma, delta), Acidobacteria, and Firmicutes were
      abundant in all soils. The abundance of Firmicutes was elevated in newer post
      mined soils relative to the un-mined soil, and this contrasted a decrease,
      relative to un-mined soils, in proteobacterial and acidobacterial rRNA gene
      abundances. Our study indicates long-lasting impacts of mining activities to soil
      biogeochemical and microbial properties with impending loss in soil productivity.

PMID- 22391799
TI  - Seasonal depth-related gradients in virioplankton: lytic activity and comparison
      with protistan grazing potential in Lake Pavin (France).
AB  - This study presents an original depth-related survey of virioplankton lytic
      activity in relation to prokaryotic production and potential protistan
      bacterivory in the deep (Z(max) = 92 m) meromictic volcanic Lake Pavin (Massif
      Central, France). The sampling strategy was designed to be representative of the
      physico-chemical gradients of the water column of the lake, and of the seasonal
      variability as well, i.e. 12 different depths sampled in triplicates from April
      to December 2005. In the space, viral lytic activity estimated from the frequency
      of visibly infected prokaryotic cells and from burst size over the study period
      generally decreased with depth. This was viewed as a paradox compared to the
      abundances of viruses and prokaryotes and to the prokaryotic production which
      increased with depth. The seasonal variability in viral lytic activity was
      correlated with prokaryotic variables (abundance and production) in the deepest
      waters, i.e. from the hypolimnion downwards. Compared to previous studies known
      from the mixolimnion, we conclude that the deep waters in Lake Pavin represent an
      exclusive environment for heterotrophic prokaryotes whose seasonal activity
      offers an optimal and unique resource for thriving viral communities, some of
      which may be typical, endemic to the ambient dark, cold and stable deep water
      masses. Overall, the main findings in the present study get well around a
      previous statement that the ecology of the deepest waters of Lake Pavin is
      essentially driven by the dark viral loop (dissolved organic matter-prokaryotes
      viruses) processes, which can sequester organic matters and nutrients for a long
      lived turnover time. This is in agreement with recent demonstrations from marine
      systems that meso- and bathypelagic waters are optimal environments for viral
      survival and proliferation.

PMID- 22391801
TI  - Triterpenoid saponins from the root of Anemone tomentosa.
AB  - Three new triterpenoid saponins, tomentoside A (1), B (2) and C (3), along with
      four known saponins (4-7) were isolated from the root of Anemone tomentosa. The
      structures of the new compounds were elucidated as 3-O-beta-D-ribopyranosyl-(1
      >3)-alpha-L-rhamnopyranosyl-(1->2)-[beta-D-glucopyranosyl-(1->4)]-alpha-L
      arabinopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl-(1->4)-beta-D
      glucopyranosyl-(1->6)-beta-D-glucopyranoside (1), 3-O-beta-D-ribopyranosyl-(1->3)
      alpha-L-rhamnopyranosyl-(1->2)-[beta-D-glucopyranosyl-(1->4)]-beta-D
      xylopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl-(1->4)-beta-D
      glucopyranosyl-(1->6)-beta-D-glucopyranoside (2) and 3-O-beta-D-galactopyranosyl
      (1->3)-alpha-L-rhamnopyranosyl-(1->2)-beta-D-xylopyranosyl oleanolic acid 28-O
      alpha-L-rhamnopyranosyl-(1->4)-beta-D-glucopyranosyl-(1->6)-beta-D
      glucopyranoside (3) on the basis of chemical and spectral evidence. In the
      oligosaccharide chains of compound 3, the characteristic D-galactose residue is a
      rare structural feature and secondly encountered among triterpenoid saponins from
      Anemone.

PMID- 22391800
TI  - Satureja khuzestanica attenuates apoptosis in hyperglycemic PC12 cells and spinal
      cord of diabetic rats.
AB  - Several studies have indicated the involvement of oxidative stress and high
      glucose-induced cell death in the development of diabetic neuropathy. Satureja
      khuzestanica has been recommended in the literature as a remedy for the treatment
      of diabetes, and also contains antioxidant agents. Here, we investigated the
      possible neuroprotective effects of Satureja khuzestanica extract (SKE) on in
      vitro and in vivo models of diabetic neuropathy pain. High-glucose-induced damage
      to pheochromocytoma (PC12) cells and in streptozotocin-induced diabetic rats was
      studied. Tail-flick and rotarod treadmill tests were used to access nociceptive
      threshold and motor coordination, respectively. Cell viability was determined by
      MTT assay. Activated caspase 3 and Bax/Bcl-2 ratio-biochemical markers of
      apoptosis-were evaluated using immunoblotting. We found that elevating the
      glucose in the medium (to 4* normal) increased cell toxicity and caspase-3
      activation in PC12 cells. Incubation with SKE (200 and 250 MUg/ml) decreased cell
      damage. Furthermore, the diabetic rats developed neuropathy, which was evident
      from thermal hyperalgesia and motor deficit. Administering SKE at a daily dose of
      between 50 and 200 mg/kg to the diabetic animals for 3 weeks ameliorated
      hyperglycemia, weight loss, hyperalgesia, and motor deficit, inhibited caspase 3
      activation, and decreased the Bax/Bcl-2 ratio. The results suggest that SKE
      exerts neuroprotective effects against hyperglycemia-induced cellular damage. The
      mechanisms of these effects may be related to (at least in part) the prevention
      of neural apoptosis, and the results suggest that Satureja has the therapeutic
      potential to attenuate side effects of diabetes, such as neuropathy.

PMID- 22391803
TI  - A history of the taxonomy and systematics of arbuscular mycorrhizal fungi
      belonging to the phylum Glomeromycota.
AB  - Arbuscular mycorrhizal fungi (AMF) are grouped in a monophyletic group, the
      phylum Glomeromycota. In this review, the history and complexity of the taxonomy
      and systematics of these obligate biotrophs is addressed by recognizing four
      periods. The initial discovery period (1845-1974) is characterized by description
      mainly of sporocarp-forming species and the proposal of a classification for
      these fungi. The following alpha taxonomy period (1975-1989) established a solid
      morphological basis for species identification and classification, resulting in a
      profuse description of new species and a need to standardize the nomenclature of
      spore subcellular structures. The cladistics period from 1990 to 2000 saw the
      first cladistic classification of AMF based on phenotypic characters only. At the
      end of this period, genetic characters played a role in defining taxa and
      elucidating evolutionary relationships within the group. The most recent
      phylogenetic synthesis period (2001 to present) started with the proposal of a
      new classification based on genetic characters using sequences of the multicopy
      rRNA genes.

PMID- 22391802
TI  - Overexpression of inducible 70-kDa heat shock protein in mouse improves
      structural and functional recovery of skeletal muscles from atrophy.
AB  - Heat shock proteins play a key regulatory role in cellular defense. To
      investigate the role of the inducible 70-kDa heat shock protein (HSP70) in
      skeletal muscle atrophy and subsequent recovery, soleus (SOL) and extensor
      digitorum longus (EDL) muscles from overexpressing HSP70 transgenic mice were
      immobilized for 7 days and subsequently released from immobilization and
      evaluated after 7 days. Histological analysis showed that there was a decrease in
      cross-sectional area of type II myofiber from EDL and types I and II myofiber
      from SOL muscles at 7-day immobilization in both wild-type and HSP70 mice. At 7
      day recovery, EDL and SOL myofibers from HSP70 mice, but not from wild-type mice,
      recovered their size. Muscle tetanic contraction decreased only in SOL muscles
      from wild-type mice at both 7-day immobilization and 7-day recovery; however, it
      was unaltered in the respective groups from HSP70 mice. Although no effect in a
      fatigue protocol was observed among groups, we noticed a better contractile
      performance of EDL muscles from overexpressing HSP70 groups as compared to their
      matched wild-type groups. The number of NCAM positive-satellite cells reduced
      after immobilization and recovery in both EDL and SOL muscles from wild-type
      mice, but it was unchanged in the muscles from HSP70 mice. These results suggest
      that HSP70 improves structural and functional recovery of skeletal muscle after
      disuse atrophy, and this effect might be associated with preservation of
      satellite cell amount.

PMID- 22391805
TI  - Alteration of selectivity in rhodamine based probes for Fe(III) and Hg(II) ion
      induced dual mode signalling responses.
AB  - The probes for metal ion induced chromo- and fluorogenic signalling responses
      alter their selectivity depending upon the nature of substituent as well as a
      function of solvent medium. 2 has shown selectivity towards Fe(III) ion, 4
      towards Hg(II) ion while 3 is responsive towards both Fe(III) and Hg(II) ions.

PMID- 22391798
TI  - Spatial heterogeneity of bacterial communities in sediments from an infiltration
      basin receiving highway runoff.
AB  - The bacterial community diversity of highway runoff-contaminated sediment that
      had undergone 19 years of acetate-based de-icing agents addition followed by
      three years of acetate-free de-icing agents was investigated. Analysis of 26
      sediment samples from two drilled soil cores by means of 16S rDNA PCR generated
      3,402 clones, indicating an overall high bacterial diversity, with no prominent
      members within the communities. Sequence analyses provided evidences that each
      sediment sample displayed a specific structure bacterial community.
      Proteobacteria-affiliated clones (58% and 43% for the two boreholes) predominated
      in all samples, followed by Actinobacteria (12% and 16%), Firmicutes (7% and 12%)
      and Chloroflexi (7% and 11%). The subsurface geochemistry complemented the
      molecular methods to further distinguish ambient and contaminant plume zones.
      Principal component analysis revealed that the levels of Fe(II) and dissolved
      oxygen were strongly correlated with bacterial communities. At elevated Fe(II)
      levels, sequences associated with anaerobic bacteria were detected in high
      levels. As iron levels declined and oxygen levels increased below the plume
      bottom, there was a gradual shift in the community structure toward the increase
      of aerobic bacteria.

PMID- 22391804
TI  - The role of phosphorus in the ectendomycorrhiza continuum of desert truffle
      mycorrhizal plants.
AB  - The influence of inorganic and organic phosphorus (P) and the absence of P in the
      culture medium on the type of mycorrhizal colonization formed (ecto-, ectendo-,
      or endomycorrhiza) during Helianthemum almeriense x Terfezia claveryi symbiosis
      in in vitro conditions was analyzed. This is the first time that the relative
      proportions of the different mycorrhizal types in mycorrhizal roots of H.
      almeriense have been quantified and statistically analyzed. The relative
      proportions of the mycorrhizal types depended on the P source in the medium,
      suggesting that it is the organic P form that induces the formation of
      intracellular colonization. The above association should be considered as a
      continuum between intra- and intercellular colonizations, the most appropriate
      term for defining it being ectendomycorrhiza. The influence of the endogenous
      concentration of P on plant growth was also analyzed. P translocation was
      observed from shoot to roots, especially in mycorrhizal plants because
      mycorrhizal roots showed higher growth than non-mycorrhizal roots and/or because
      of an extra P demand from mycelium inside the roots. Soluble and cell wall acid
      phosphatases activities from H. almeriense roots were kinetically characterized
      at optimum pH (5.0), using p-nitrophenyl phosphate as substrate, with K (m)
      values of 3.4 and 1.8 mM, respectively. Moreover, the plant acid phosphatase and
      fungal alkaline phosphatases activities were histochemically localised in
      mycorrhizal H. almeriense roots by fluorescence with enzyme-labelled fluorescence
      substrate.

PMID- 22391807
TI  - Design of iron chelators with therapeutic application.
AB  - Iron is essential for the proper functioning of all living cells, however it is
      toxic when present in excess. Thus, using iron chelators as therapeutic agents,
      namely chelation therapy, has received increasing attention. The objective of
      this review is to discuss the factors which should be considered when designing
      clinically useful iron chelators, to present the application of iron chelators in
      the treatment of iron overload associated with beta-thalassaemia major and sickle
      cell anaemia, and to highlight the potential applications in the treatment of
      neurodegenerative disorders and microbial infection. This article reviews recent
      knowledge centred on these themes and indicates the growing importance of the
      concept of iron chelation in medicine.

PMID- 22391806
TI  - Class II major histocompatibility complex-associated response to type XI collagen
      regulates the development of chronic arthritis in rats.
AB  - OBJECTIVE: Chronic inflammation of the peripheral joints is a hallmark of
      rheumatoid arthritis (RA). The autoantibody response in RA has been shown to be
      directed mainly to ubiquitous antigens, whereas the response to cartilage
      proteins has been less extensively investigated. This study was undertaken to
      characterize the immune response in pristane-induced arthritis (PIA) in the rat
      to the cartilage-specific proteins type II collagen (CII) and type XI collagen
      (CXI) and to genetically fine-map their underlying major histocompatibility
      complex (MHC) associations. METHODS: The genetic control of CII and CXI immunity
      was mapped using intra-MHC-recombinant inbred strains immunized with the
      respective collagens. Reactivity with CII and CXI was tested in acute and chronic
      PIA and in 356 HLA-typed patients with recently diagnosed RA. RESULTS: Mapping of
      arthritis susceptibility within the MHC region revealed a 144-223-kb locus
      containing <12 genes, including paralogs for HLA-DQ and HLA-DR. Susceptibility to
      CII and CXI was linked to haplotypes RT1(av1)  (DA) and RT1(f)  (DA.1F),
      respectively. After injection of pristane, rats of both strains developed weak T
      cell and IgG responses to CII, but not to CXI. In chronic arthritis, however,
      collagen reactivity was stronger, specific for CXI, and restricted to rats with
      RT1(f)  MHC. Among RA patients, 12% exhibited a specific IgG response to CXI, 6%
      to CII, and 6% to both collagens. CONCLUSION: These findings demonstrate a shift
      in cartilage recognition in early and chronic arthritis in the rat, suggesting
      that CXI autoreactivity contributes to the perpetuation of chronic disease. The
      results provide evidence of the importance of joint antigens in arthritis
      development.

PMID- 22391808
TI  - The 2nd Biennial Eurasian Colorectal Technologies Association (ECTA) Meeting.

PMID- 22391809
TI  - Reasoning on the basis of fantasy content: two studies with high-functioning
      autistic adolescents.
AB  - Reasoning about problems with empirically false content can be hard, as the
      inferences that people draw are heavily influenced by their background knowledge.
      However, presenting empirically false premises in a fantasy context helps
      children and adolescents to disregard their beliefs, and to reason on the basis
      of the premises. The aim of the present experiments was to see if high
      functioning adolescents with autism are able to utilize fantasy context to the
      same extent as typically developing adolescents when they reason about
      empirically false premises. The results indicate that problems with engaging in
      pretence in autism persist into adolescence, and this hinders the ability of
      autistic individuals to disregard their beliefs when empirical knowledge is
      irrelevant.

PMID- 22391810
TI  - Flexible visual processing in young adults with autism: the effects of implicit
      learning on a global-local task.
AB  - We utilized a hierarchical figures task to determine the default level of
      perceptual processing and the flexibility of visual processing in a group of high
      functioning young adults with autism (n = 12) and a typically developing young
      adults, matched by chronological age and IQ (n = 12). In one task, participants
      attended to one level of the figure and ignored the other in order to determine
      the default level of processing. In the other task, participants attended to both
      levels and the proportion of trials in which a target would occur at either level
      was manipulated. Both groups exhibited a global processing bias and showed
      similar flexibility in performance, suggesting that persons with autism may not
      be impaired in flexible shifting between task levels.

PMID- 22391811
TI  - Examining the specific effects of context on adaptive behavior and achievement in
      a rural African community: six case studies from rural areas of Southern
      province, Zambia.
AB  - Generally accepted as universal, the construct of adaptive behavior differs in
      its manifestations across different cultures and settings. The Vineland-II
      (Sparrow et al. in Vineland Adaptive Behavior Scales, Second edn. AGS Publishing,
      Circle Pines, MN, 2005) was translated into Chitonga and adapted to the setting
      of rural Southern Province, Zambia. This version was administered to the
      parents/caregivers of 114 children (grades 3-7, mean age = 12.94, SD = 2.34). The
      relationships between these children's adaptive behavior, academic achievement
      and cognitive ability indicators are compared to those usually observed in US
      samples. Results reflect no association between adaptive behavior and cognitive
      ability indicators, but a strong relationship between high adaptive behavior and
      reading-related measures. Six case studies of children with high and low scores
      on the Vineland-II are presented to illustrate the possible factors affecting
      these outcomes. 

PMID- 22391814
TI  - Modulation of T-cell function by type I interferon.
AB  - Production of type I interferon (IFN-alpha/beta) is a common cellular response to
      virus infection. IFN-alpha/beta has a dual role in combating infection,
      triggering innate antiviral mechanisms and stimulating the generation of an
      adaptive immune response. This review focuses on the effects of IFN-alpha/beta on
      one particular immune cell type, the T cell, and the impact of IFN-alpha/beta
      mediated signalling in T cells on the immune response. The critical role of T
      cell responsiveness to IFN-alpha/beta for the generation of productive T-cell
      responses after infections with certain viruses in vivo is discussed in the
      context of in vitro experiments investigating the mechanisms by which IFN
      alpha/beta modifies T-cell function. These studies reveal complex effects of IFN
      alpha/beta on T cells, with the consequences of exposure to IFN-alpha/beta
      depending on the context of other signals received by the T cell.

PMID- 22391813
TI  - Yin Yang-1 suppresses differentiation of hepatocellular carcinoma cells through
      the downregulation of CCAAT/enhancer-binding protein alpha.
AB  - As a member of the GLI-Kruppel family of transcriptional factors, Yin Yang-1
      (YY1) functions as an oncogene in various types of cancers. However, the role of
      YY1 in hepatocellular carcinogenesis remains unknown. In this report, we
      investigated the relevance of YY1 to hepatocellular carcinoma (HCC) development.
      We found that YY1 was upregulated in HCC cell lines. Ectopic YY1 expression
      promoted the growth of non-tumor liver cells that expressed low level of YY1. In
      contrast, YY1 depletion inhibited the growth of HCC cells which was accompanied
      with distinct morphological changes. Moreover, the phenotypic changes induced by
      YY1 depletion were attributed to cellular differentiation rather than cellular
      senescence. CCAAT/enhancer-binding protein alpha (CEBPA) which was important to
      regulate differentiation of hepatocytes was found as the direct target
      downregulated by YY1. Restoration of CEBPA in YY1-expressing HCC cells induced
      cellular differentiation and growth inhibition while knockdown of CEBPA
      expression in non-tumor liver cells promoted cell growth. In summary, our study
      demonstrated that YY1 could promote hepatocellular carcinogenesis and inhibit
      cellular differentiation through the downregulation of CEBPA expression.

PMID- 22391815
TI  - Impaired ability of burn patient neutrophils to stimulate beta-defensin
      production by keratinocytes.
AB  - Immunosuppressive neutrophils (PMN-II) appearing in association with burn injury
      have a role on the increased susceptibility of burn patients to various
      infections. In the present study, the role of PMN-II on the production of human
      beta-defensins (HBDs), important molecules on host antimicrobial innate
      immunities, by human keratinocytes was studied. Normal human epidermal
      keratinocytes (NHEKs) were cultured with neutrophils (PMNs) isolated from burn
      patients or healthy volunteers in dual-chamber transwells. Culture fluids
      harvested 24 h after cultivation were assayed for HBDs using enzyme-linked
      immunosorbent assay. Also, these culture fluids were assayed for their
      antimicrobial activities by a standard colony-counting method using Pseudomonas
      aeruginosa. In the results, PMNs isolated from peripheral blood of burn patients
      were confirmed as PMN-II, because these cells produced CC-chemokine ligand 2
      (CCL2), but not interleukin (IL)-12 and CC-chemokine ligand 3 (CCL3). Culture
      fluids of NHEK transwell-cultured with healthy PMNs exhibited strong killing
      activities against P. aeruginosa (96% inhibition), however, the growth of
      bacteria was not dramatically inhibited by the culture fluids of NHEK transwell
      cultured with burn-patient PMNs (36% inhibition). IL-12 and CCL3 containing
      culture fluids of healthy PMNs stimulated with the bacterial antigen or rCCL3 and
      rIL-12 enhanced the production of HBD2 and HBD3 by NHEK, whereas CCL2 containing
      culture fluids of burn-patient PMN stimulated with the antigen or rCCL2 inhibited
      the HBD production by NHEK. These results indicate that PMN-II appearing in
      association with burn injury contribute to the decreased production of HBDs in
      thermally injured patients.

PMID- 22391816
TI  - Acute coronary syndrome or apical ballooning syndrome?
AB  - Apical ballooning syndrome (ABS) is uniquely characterized by the acute onset of
      transient extensive kinesis of the apical and mid portions of the left ventricle
      without significant epicardial coronary artery stenosis, accompanied by chest
      symptoms and electrocardiogram changes similar to those of acute coronary
      syndrome. We report a case of ABS with severe coronary artery stenosis presenting
      as acute coronary syndrome after emotional stress. ABS should be considered a
      cause of left ventricular wall motion abnormalities even if a coronary
      arteriogram shows severe coronary artery stenosis.

PMID- 22391817
TI  - EU commissioner says he will tighten laws to make cigarette packs less
      attractive.

PMID- 22391818
TI  - People over 65 should be screened for atrial fibrillation, say stroke
      specialists.

PMID- 22391819
TI  - Europe issues proposals to bring drugs to market faster.

PMID- 22391820
TI  - TB and HIV services must be fully integrated, says WHO.

PMID- 22391821
TI  - Lipoma arborescens.

PMID- 22391822
TI  - Protective effect of rPb40 as an adjuvant for chemotherapy in experimental
      paracoccidioidomycosis.
AB  - The conventional treatment for the most prevalent mycosis in Latin America,
      paracoccidioidomycosis (PCM), involves long periods of therapy that results in
      side effects and a high frequency of relapses. The search for a new, alternative
      treatment is necessary. Pb40 is an antigenic protein from P. brasiliensis
      fraction F0. This fraction has already been shown to have significant protective
      activity when used as a PCM vaccine in experimental models. The complete cDNA
      sequence corresponding to Pb40 was cloned into a pET-21a plasmid, expressed in E.
      coli with a his-tag and purified by affinity chromatography. The predicted
      protein sequence exhibited nearly 100% homology to a fragment of the hypothetical
      EF-hand domain containing protein of P. brasiliensis. Immunization with this
      recombinant protein was used together with chemotherapy in an attempt to improve
      PCM treatment. The combined drug/rPb40 treatment exhibited long-lasting control
      of PCM in the liver and spleen and largely preserved the tissue structures of
      these organs. Despite the lack of a reduction in CFUs in the group that received
      the combined treatment, there was a significant reduction in the size of the
      lesions in the lungs after 70 days of infection. At the same time, the IL-10
      levels were higher in the treated mice than in the infected-only mice. Moreover,
      significant levels of rPb40-specific IgG antibodies were detected in the sera of
      immunized mice. Thus, the treatment protocol consisting of rPb40 immunization in
      addition to fluconazole chemotherapy showed an additive protective effect after
      intratracheal challenge, preventing fungal dissemination to other sites of
      infection and preventing relapses. These results provide new prospects for PCM
      immunotherapy.

PMID- 22391824
TI  - Patients undergoing frozen-thawed embryo transfer have similar live birth rates
      in spontaneous and artificial cycles.
AB  - PURPOSE: To evaluate the outcome of frozen-thawed embryo transfer (FET) when
      freezing takes place at the pronuclear stage, a retrospective analysis was
      performed comparing spontaneous and artificial cycles. METHODS: 148 women
      received FET in a spontaneous cycle (Group A) and 55 women received FET in an
      artificial cycle (Group B) induced by administering estrogen (E2) and
      progesterone (P). Pregnancy rates, endometrial thickness and serum levels of E2,
      P and luteinizing hormone (LH) were measured. Statistical analysis included the
      mean, the standard deviation, the Chi-squared test and the T-test. RESULTS: The
      clinical pregnancy rate was 34.5% for Group A and 21.8% for Group B (p = 0.084),
      with a live birth rate of 20.9% and 12.7% respectively (p = 0.15). There was no
      difference in endometrial thickness or the P levels, while LH and E2 levels were
      significantly higher in group B (p < 0.0001). CONCLUSION: Our retrospective study
      shows a trend towards higher pregnancy rates and live birth rates with the
      administration of FET during a spontaneous cycle compared to FET during an
      artificial cycle. Large randomized controlled trials are needed to confirm this
      trend.

PMID- 22391823
TI  - Deletion of the Candida albicans PIR32 results in increased virulence, stress
      response, and upregulation of cell wall chitin deposition.
AB  - Candida albicans is a common opportunistic pathogen that causes a wide variety of
      diseases in a human immunocompromised host leading to death. In a pathogen, cell
      wall proteins are important for stability as well as for acting as antigenic
      determinants and virulence factors. Pir32 is a cell wall protein and member of
      the Pir protein family previously shown to be upregulated in response to
      macrophage contact and whose other member, Pir1, was found to be necessary for
      cell wall rigidity. The purpose of this study is to characterize Pir32 by
      generating a homozygous null strain and comparing the phenotype of the null with
      that of the wild-type parental strain as far as filamentation, virulence in a
      mouse model of disseminated candidiasis, resistance to oxidative stress and cell
      wall disrupting agents, in addition to adhesion, biofilm capacities, and cell
      wall chitin content. Our mutant was shown to be hyperfilamentous, resistant to
      sodium dodecyl sulfate, hydrogen peroxide, sodium chloride, and more virulent in
      a mouse model when compared to the wild type. These results were unexpected,
      considering that most cell wall mutations weaken the wall and render it more
      susceptible to external stress factors and suggests the possibility of a cell
      surface compensatory mechanism. As such, we measured cell wall chitin deposition
      and found a twofold increase in the mutant, possibly explaining the above
      observed phenotypes.

PMID- 22391825
TI  - Cryopreservation of individually selected sperm: methodology and case report of a
      clinical pregnancy.
AB  - OBJECTIVE: To describe a new technique for freezing individually isolated
      spermatazoa from testicular biopsies, epididymal aspirates and oligospermic semen
      samples METHODS: Samples were evaluated for the presence of motile sperm before
      cryopreservation. Motile or twitching sperm were isolated with an ICSI needle for
      single sperm cryopreservation. Selected sperm were loaded on the High Security
      Straw (HSV; Irvine Scientific; Irvine,CA), in ~0.5 ul of fluid to facilitate
      recovery. The sample was also frozen using conventional methodology in cryovials
      (100-1000 ul aliquots). In both freezing techniques, the samples were slow
      cooled. Test-yolk buffer-glycerol (Irvine) was used as the cryoprotectant. Test
      thaws were performed to assess sperm recovery and motility. RESULTS: Six men with
      azoospermia had single sperm cryopreservation, as well as freezing aliquots of
      their testicular or epididymal sperm in traditional cryovials. In addition, two
      men with oligospermia also had individual sperm selected and frozen. In all 8
      cases, the ~0.5 ul of fluid containing sperm was quite easily unloaded from the
      HSV straw during thawing. The percent sperm recovery ranged from 33% to 100%.
      Motility was evident in all but one sample. In six cases, the sperm were used for
      intracytoplasmic sperm injection of mature oocytes. Fertilization occurred in all
      but one case. In this study, we report the first clinical pregnancy with this
      technique. This pregnancy was remarkable in that a single motile sperm identified
      and selected in the initial testicular preparation was successfully frozen. We
      were able to subsequently recover this sperm, fertilize an oocyte and the
      resultant embryo gave rise to a live birth. The methodology described in this
      preliminary report offers a new modality for sequestering small numbers of sperm.
      It may be particularly useful in cases involving severe impairment of
      spermatogenesis, where extensive screening may be necessary to find a few viable
      sperm.

PMID- 22391826
TI  - Capillary refill time is a very useful clinical sign in early recognition and
      treatment of very sick children.

PMID- 22391827
TI  - Exhaled breath condensate: a breathalyzer for lung inflammation.

PMID- 22391828
TI  - Family presence: not a panacea for all.

PMID- 22391829
TI  - Mechanical ventilation during the season for acute lower respiratory infection:
      too much or too little?.

PMID- 22391830
TI  - Preventing a CRISIS: no magic cocktail yet.

PMID- 22391831
TI  - Racial disparities in congenital heart disease: beyond red and blue.

PMID- 22391832
TI  - Respiratory distress syndrome and acute respiratory distress syndrome: can early
      diagnosis facilitate a better outcome?.

PMID- 22391833
TI  - Infections and brain injuries: beginning to understand the association.

PMID- 22391834
TI  - When persistent pulmonary hypertension of the newborn persists.

PMID- 22391835
TI  - Weathering the perfect storm: a deeper look at simulation applied to pediatric
      critical care.

PMID- 22391836
TI  - Occult sinusitis in the pediatric intensive care unit.

PMID- 22391837
TI  - Catheter-associated bloodstream infections: primum non nocere (firstly, do no
      harm).

PMID- 22391839
TI  - pH1N1: predictions may go south so please do not bet.

PMID- 22391838
TI  - Vulnerability to pediatric sepsis: all in the genes?.

PMID- 22391840
TI  - New hopes and better treatment prospects for patients with neuromuscular
      pathologies and respiratory failure?.

PMID- 22391841
TI  - A warning from India: hypovolemia may be as dangerous as excessive fluid infusion
      for cerebral edema in diabetic ketoacidosis.

PMID- 22391842
TI  - Chest physiotherapy: how does it work (if it does)?.

PMID- 22391843
TI  - 'De hydration' assessment and replacement fluid therapy in diabetic ketoacidosis:
      is there an answer?.

PMID- 22391844
TI  - High-frequency oscillatory ventilation: learning which way to turn the dials.

PMID- 22391845
TI  - Antioxidants in pediatric sepsis: do not put the plough in front of the horses!.

PMID- 22391846
TI  - Have a couple of minutes? Probably not.

PMID- 22391847
TI  - Invasive arterial pressure: test it before believing in!

PMID- 22391848
TI  - The removal-associated sepsis prevention trial in preterm newborns was ended in
      an untimely manner.

PMID- 22391849
TI  - Chest compression vibrations and manual hyperinflation in pediatric patients.

PMID- 22391851
TI  - The pulmonary artery catheter in the pediatric intensive care unit: not the way
      to go.

PMID- 22391852
TI  - Risk factors for cerebral edema in diabetic ketoacidosis in a developing country:
      role of fluid refractory shock.
AB  - OBJECTIVES: To study the clinical profile and risk factors of cerebral edema in
      children with diabetic ketoacidosis with specific reference to fluid refractory
      shock. DESIGN: Retrospective review of medical records. SETTING: Twelve-bed
      pediatric intensive care unit of a teaching hospital. PATIENTS: Seventy-seven
      patients admitted to pediatric intensive care unit with a diagnosis of diabetic
      ketoacidosis over 5 yrs. INTERVENTION: Medical records were reviewed, and data
      with respect to patients' age, clinical features, biochemical profile (blood
      glucose, osmolality, electrolytes, urea, creatinine, arterial pH, PaCO(2), and
      HCO(3) at admission, 6-12 hrs, 24 hrs, and beyond 24 hrs), cerebral edema,
      presence of sepsis and shock, treatment details, and primary outcome in terms of
      survival or death were retrieved. Patients with and without cerebral edema were
      compared. Variables that were significant on univariate analysis were entered in
      a multiple logistic regression analysis to determine the predictors for cerebral
      edema. Odds ratio and 95% confidence interval were calculated using SPSS version
      15. MEASUREMENTS AND MAIN RESULTS: Mean age of the patients was 5.6 (standard
      deviation, 3.8) years. Fifty-five (71.4%) patients had new-onset diabetes
      mellitus. Cerebral edema was seen in 20 patients (26%). Blood glucose, serum
      osmolality, and CO(2) values at admission and rate of decline in glucose and
      osmolality during the first 12 hrs were similar in the cerebral edema and
      noncerebral edema groups. On multiple logistic regression analysis, fluid
      refractory shock (odds ratio, 7.3; 95% confidence interval, 1.3-41; p = .025) and
      presence of azotemia (odds ratio, 4.3; 95% confidence interval, 1.1-16; p = .034)
      at admission were predictors for development of cerebral edema. Mortality in
      cerebral edema group was 25% as compared to 3% in the noncerebral edema group.
      CONCLUSIONS: Patients with fluid refractory shock and azotemia at admission had
      higher odds for development of cerebral edema. Initial blood glucose, effective
      osmolality, or decline in glucose and osmolality had no association with cerebral
      edema.

PMID- 22391853
TI  - [The joys and sorrows of congress presentations].

PMID- 22391854
TI  - Combined effects of quercetin and atenolol in reducing isoproterenol-induced
      cardiotoxicity in rats: possible mediation through scavenging free radicals.
AB  - In this investigation, combined effects of quercetin and atenolol in the
      regulation of isoproterenol (ISO)-induced cardiotoxicity have been evaluated in
      rats. While ISO administration increased the levels of serum creatine kinase-MB
      (CK-MB), lactate dehydrogenase (LDH) and glutamate pyruvate transaminase (SGPT)
      as well as cardiac malondialdehyde (MDA); it reduced the activities of superoxide
      dismutase, catalase, glutathione peroxidase and the level of reduced glutathione.
      ISO-induced rats also exhibited ST-segment elevation and tachycardia. Oral
      administration of atenolol (6 mg/kg) and quercetin (5 mg/kg), along with ISO (5
      mg/kg, subcutaneously) every day for 10 days markedly reduced the serum CK-MB,
      LDH and SGPT levels. Concomitantly the test drugs improved the status of
      antioxidative enzymes, decreased the cardiac MDA and nearly normalized the
      electrocardiogram. Electron paramagnetic resonance study also revealed a decrease
      in 5,5'-dimethyl-1-pyroline-N-oxide-hydroxyl radicals signal intensity when
      atenolol and quercetin were administered together to ISO-treated rats. In
      conclusion, the combined treatment of atenolol and quercetin appears to produce a
      better cardioprotective effect in ISO-induced animals as compared to their
      individual treatments, and possibly the beneficial actions are associated with
      the free radical scavenging action of quercetin.

PMID- 22391855
TI  - Methylation effect on chalcone synthase gene expression determines anthocyanin
      pigmentation in floral tissues of two Oncidium orchid cultivars.
AB  - The anthocyanin-biosynthetic pathway was studied in flowers of Oncidium Gower
      Ramsey with yellow floral color and mosaic red anthocyanin in lip crests, sepals
      and petals, and compared with the anthocyanin biosynthesis in flowers of Oncidium
      Honey Dollp, a natural somatoclone derived from tissue culture of Gower Ramsey,
      with a yellow perianth without red anthocyanins in floral tissues. HPLC analysis
      revealed that the red anthocyanin in lip crests of the Gower Ramsey cultivar
      comprised peonidin-3-O-glucoside, delphinidin-3-O-glucoside and cyanidin-3-O
      glucoside, whereas Honey Dollp was devoid of anthocyanin compounds. Among the
      five anthocyanin-biosynthetic genes, OgCHS was actively expressed in lip crests
      of Gower Ramsey flowers, but no transcripts of OgCHS were detected in Honey Dollp
      floral tissues. Transient expression of OgCHS by bombardment confirmed that
      recovery of the OgCHS gene expression completed the anthocyanin pathway and
      produced anthocyanin compounds in lip crests of Honey Dollp flowers.
      Transcription factor genes regulating anthocyanin biosynthesis showed no
      distinctive differences in the expression level of OgMYB1, OgbHLH and OgWD40
      between the two cultivars. A methylation assay revealed that the promoter of
      OgCHS was not methylated in Gower Ramsey, while a positive methylation effect was
      present in the upstream promoter region of OgCHS in Honey Dollp. Overall, our
      results suggest that the failure of anthocyanin accumulation in Honey Dollp
      floral tissues may be attributed to inactivation of the OgCHS gene resulting from
      the epigenetic methylation of 5'-upstream promoter region.

PMID- 22391856
TI  - A mutation in the E2 subunit of the mitochondrial pyruvate dehydrogenase complex
      in Arabidopsis reduces plant organ size and enhances the accumulation of amino
      acids and intermediate products of the TCA cycle.
AB  - The mitochondrial pyruvate dehydrogenase complex (mtPDC) plays a pivotal role in
      controlling the entry of carbon into the tricarboxylic acid (TCA) cycle for
      energy production. This multi-enzyme complex consists of three components: E1,
      E2, and E3. In Arabidopsis, there are three genes, mtE2-1, mtE2-2, and mtE2-3,
      which encode the putative mtPDC E2 subunit but how each of them contributes to
      the total mtPDC activity remains unknown. In this work, we characterized an
      Arabidopsis mutant, m132, that has abnormal small organs. Molecular cloning
      indicated that the phenotype of m132 is caused by a mutation in the mtE2-1 gene,
      which results in a truncation of 109 amino acids at the C-terminus of the encoded
      protein. In m132, mtPDC activity is only 30% of the WT and ATP production is
      severely impaired. The mutation in the mtE2-1 gene also leads to the over
      accumulation of most intermediate products of the TCA cycle and of all the amino
      acids for protein synthesis. Our results suggest that, among the three mtE2
      genes, mtE2-1 is a major contributor to the function of Arabidopsis mtPDC and
      that the functional disruption of mtE2-1 profoundly affects plant growth and
      development, as well as its metabolism.

PMID- 22391857
TI  - A seminaphthofluorescein-based fluorescent chemodosimeter for the highly
      selective detection of cysteine.
AB  - A fluorescent chemodosimeter for cysteine detection was developed based on a
      tandem conjugate addition and intramolecular cyclization reaction. The method
      exhibited an excellent selectivity for cysteine over other biothiols such as
      homocysteine and glutathione.

PMID- 22391858
TI  - An investigation of the correlation between blood concentration of mizoribine and
      its efficacy in treatment of rheumatoid arthritis based on indices of drug
      survival and improvement in DAS28-CRP.
AB  - OBJECTIVES: The efficacy of mizoribine (MZR) in treatment of rheumatoid arthritis
      (RA) was retrospectively investigated in terms of drug survival, improvement in
      Disease Activity Score-28 (DAS28)-C-reactive protein (CRP), and blood MZR
      concentration obtained 3 h after dosing (MZR-C3). METHODS: To compare the
      efficacy of MZR administered via different regimens, the subjects were divided
      into 2 groups: those receiving a single dose of MZR at 100-150 mg every other day
      (group A) and those receiving 2 or 3 divided doses of the drug on consecutive
      days, which is the usual dosing method of the drug (group B). RESULTS: Group A
      had significantly higher MZR-C3 levels compared with group B, as well as
      significantly greater improvement in DAS28-CRP. Moreover, drug survival was
      significantly longer in group A. The primary regression equation suggested that
      the effective blood MZR concentration in RA treatment is MZR-C3 of 1.47 ug/mL or
      more. CONCLUSIONS: The results of the present study indicate that it is possible
      to increase the efficacy of MZR in a blood concentration-dependent manner, and
      also to control RA over a prolonged period, using single administration of MZR on
      alternate days at an increased dose.

PMID- 22391859
TI  - Color flow signals of six-joint Doppler sonography correlate with disease
      activity in patients with rheumatoid arthritis.

PMID- 22391860
TI  - ANCA-associated vasculitis with dual ANCA positivity in coexistence with mixed
      connective tissue disease.
AB  - We here report a rare case of dual antineutrophil cytoplasmic antibody (ANCA)
      associated vasculitis (AAV) in a 38-year-old Japanese woman previously diagnosed
      with mixed connective tissue disease. The patient was found to be positive for
      myeloperoxidase- and proteinase 3-ANCA, and was diagnosed with AAV following
      admission to hospital with fervescence, polyarthralgia, purpura, and asymmetric
      numbness of the extremities. Examination of her genetic background revealed that
      she carried HLA-DR9, which confers risk of both diseases in Japanese populations.

PMID- 22391861
TI  - Importance of CT scans in diagnosing symptoms from misplaced implants.
AB  - Maxillary sinus or nasal cavity invasion with implants might not be detected
      during implant placement. However, these complications cause problems in the long
      run. In the following two cases, maxillary sinus and nasal cavity invasion with
      misplaced implants could not be detected with panoramic and periapical
      radiographs; the patients had to undergo several prosthetic and surgical
      procedures to have their problems resolved. These problems were detected with CT
      imaging technique. For the first patient, the misplaced implant was removed and a
      new prosthesis was fabricated on the remaining implants. The prosthetic treatment
      of the second patient was finalized with new implants placed in the removed
      implant sites, and a new metal-resin implant-fixed complete dental prosthesis was
      fabricated.

PMID- 22391862
TI  - Effect of using a titanium washer on the removal torque of an abutment screw in
      the external connection type of dental implant.
AB  - PURPOSE: The aim of this study was to determine the effect of using a washer on
      the removal torque of an abutment screw in the external connection type of dental
      implant and abutment complex. MATERIALS AND METHODS: Four experimental groups
      with titanium washers of different types (CP titanium or Ti6Al4V titanium alloy)
      and thicknesses (1.0 or 2.0 mm) included between the abutment and external
      connection type of implant were investigated. No washer was applied in the
      control group. The removal torque was measured with a resolution of 0.1 Ncm. One
      way analysis of variance (alpha = 0.05) and Scheffe's post hoc test were used for
      statistical analysis. RESULTS: The removal torque was higher in all the groups
      with a washer than in the control group (alpha = 0.05), higher with a CP titanium
      washer than with a titanium alloy washer of the same thickness, and higher with a
      2.0-mm-thick washer than with a 1.0-mm-thick washer (alpha = 0.05). CONCLUSIONS:
      Inclusion of a washer between the titanium screw and the abutment seems to
      increase the removal torque. A 2.0-mm-thick CP titanium washer might provide the
      largest increase in the removal torque.

PMID- 22391863
TI  - S-nitrosoglutathione prevents experimental cerebral malaria.
AB  - Administration of the exogenous nitric oxide (NO) donor dipropylenetriamine
      NONOate (DPTA-NO) to mice during Plasmodium berghei ANKA (PbA) infection largely
      prevents development of experimental cerebral malaria (ECM). However, a high dose
      (1 mg/mouse twice a day) is necessary and causes potent side effects such as
      marked hypotension. In the present study we evaluated whether an alternative,
      physiologically relevant NO donor, S-nitrosoglutathione (GSNO), was able to
      prevent ECM at lower doses with minimal side effects. Prophylactic treatment with
      high (3.5 mg), intermediate (0.35 mg) or low (0.035 mg) doses of GSNO decreased
      incidence of ECM in PbA-infected mice, decreasing also edema, leukocyte
      accumulation and hemorrhage incidence in the brain. The high dose inhibited
      parasite growth and also induced transient hypotension. Low and intermediate
      doses had no or only mild effects on parasitemia, blood pressure, and heart rate
      compared to saline-treated mice. PbA infection decreased brain total and reduced
      (GSH) glutathione levels. Brain levels of oxidized (GSSG) glutathione and the
      GSH/GSSG ratio were positively correlated with temperature and motor behavior.
      Low and intermediate doses of GSNO failed to restore the depleted brain total
      glutathione and GSH levels, suggesting that ECM prevention by GSNO was probably
      related to other effects such as inhibition of inflammation and vascular
      protection. These results indicate that ECM is associated with depletion of the
      brain glutathione pool and that GSNO is able to prevent ECM development in a wide
      range of doses, decreasing brain inflammation and inducing milder cardiovascular
      side effects.

PMID- 22391866
TI  - Comparison between continuous and discontinuous multiple vertebral compression
      fractures.
AB  - BACKGROUND: The majority of multiple vertebral fractures (MVFs) occur under high
      energy conditions; however, some cases occurring under minor-energy conditions
      exist. Fractures in successive vertebrae (continuous type) and in skipped
      vertebrae (discontinuous type) can exist. PURPOSE: The objective of this study
      was to compare and evaluate the cause, level of injury, and relationship to
      osteoporosis between continuous and discontinuous MVFs. METHODS: We studied 77
      subjects (173 vertebrae) who had presented with acute back pain between September
      2007 and April 2010 and who received diagnoses of fresh MVFs through magnetic
      resonance imaging. Subjects with continuous and discontinuous fractures were
      evaluated based on age, sex, bone mineral density (BMD), level of affected
      vertebrae, and cause of injury. RESULTS: Subjects with discontinuous MVFs were
      significantly older and comprised more female patients. Mean BMD, measured by
      dual-emission X-ray absorptiometry, was 0.70 and 0.58 g/cm(3) for the continuous
      and discontinuous MVFs, respectively, demonstrating a significant difference. Of
      34 patients with discontinuous MVFs, 32 (94%) exhibited vertebral fractures in
      the thoracolumbar junction. In subjects with continuous MVFs, the MVFs of 19
      (44%) subjects were caused by high-energy trauma, whereas mild trauma and unknown
      cause were identified in 14 (41%) and 13 (38%) subjects with discontinuous MVFs,
      respectively. CONCLUSIONS: Discontinuous MVFs generally caused by mild outer
      force, and often occurred at the thoracolumbar junction. Continuous MVFs,
      frequently, were caused by high-energy trauma.

PMID- 22391864
TI  - Prefrontal dopaminergic and enkephalinergic synaptic accommodation in HIV
      associated neurocognitive disorders and encephalitis.
AB  - Changes in synapse structure occur in frontal neocortex with HIV encephalitis
      (HIVE) and may contribute to HIV-associated neurocognitive disorders (HAND). A
      postmortem survey was conducted to determine if mRNAs involved in synaptic
      transmission are perturbed in dorsolateral prefrontal cortex (DLPFC) in subjects
      with HIVE or HAND. Expression of the opioid neurotransmitter preproenkephalin
      mRNA (PENK) was significantly decreased in a sampling of 446 brain specimens from
      HIV-1 infected people compared to 67 HIV negative subjects. Decreased DLPFC PENK
      was most evident in subjects with HIVE and/or increased expression of interferon
      regulatory factor 1 mRNA (IRF1). Type 2 dopamine receptor mRNA (DRD2L) was
      decreased significantly, but not in the same set of subjects with PENK
      dysregulation. DRD2L downregulation occurred primarily in the subjects without
      HIVE or neurocognitive impairment. Subjects with neurocognitive impairment often
      failed to significantly downregulate DRD2L and had abnormally high IRF1
      expression. CONCLUSION: Dysregulation of synaptic preproenkephalin and DRD2L in
      frontal neocortex can occur with and without neurocognitive impairment in HIV
      infected people. Downregulation of DRD2L in the prefrontal cortex was associated
      with more favorable neuropsychological and neuropathological outcomes; the
      failure to downregulate DRD2L was significantly less favorable. PENK
      downregulation was related neuropathologically to HIVE, but was not related to
      neuropsychological outcome independently. Emulating endogenous synaptic
      plasticity pharmacodynamically could enhance synaptic accommodation and improve
      neuropsychological and neuropathological outcomes in HIV/AIDS.

PMID- 22391867
TI  - Neuroprotective therapy using granulocyte colony-stimulating factor for acute
      spinal cord injury: a phase I/IIa clinical trial.
AB  - OBJECTIVE: Granulocyte colony-stimulating factor (G-CSF) is a cytokine that is
      clinically used to treat neutropenia. G-CSF also has non-hematopoietic functions
      and could potentially be used to treat neuronal injury. To confirm the safety and
      feasibility of G-CSF administration for acute spinal cord injury (SCI), we have
      initiated a phase I/IIa clinical trial of neuroprotective therapy using G-CSF.
      METHODS: The trial included a total of 16 SCI patients within 48 h of onset. In
      the first step, G-CSF (5 MUg/kg/day) was intravenously administered for 5
      consecutive days to 5 patients. In the second step, G-CSF (10 MUg/kg/day) was
      similarly administered to 11 patients. We evaluated motor and sensory functions
      of patients using the American Spinal Cord Injury Association (ASIA) score and
      ASIA impairment scale (AIS) grade. RESULTS: In all 16 patients, neurological
      improvement was obtained after G-CSF administration. AIS grade increased by one
      step in 9 of 16 patients. A significant increase in ASIA motor scores was
      detected 1 day after injection (P < 0.01), and both light touch and pin prick
      scores improved 2 days after injection (P < 0.05) in the 10 MUg group. No severe
      adverse effects were observed after G-CSF injection. CONCLUSION: These results
      indicate that intravenous administration of G-CSF (10 MUg/kg/day) for 5 days is
      essentially safe, and suggest that some neurological recovery may occur in most
      patients. We suggest that G-CSF administration could be therapeutic for patients
      with acute SCI.

PMID- 22391868
TI  - High-intensity zone (HIZ) of lumbar intervertebral disc on T2-weighted magnetic
      resonance images: spatial distribution, and correlation of distribution with low
      back pain (LBP).
AB  - OBJECTIVES: To analyze the three-dimensional distribution of high-intensity zone
      (HIZ) in lumbar disks and to assess the correlation between low back pain (LBP)
      and spatial distribution of HIZs. METHODS: Clinical records and lumbar MRIs of
      623 patients (337 males and 286 females, age 50.10 +/- 15.38 years) were selected
      and reviewed. Baseline characteristics and 3D localization were performed and
      recorded by two radiologists in a blind fashion. RESULTS: Among the 623 patients,
      200 exhibited an HIZ in at least one disk. HIZs were more frequently seen in the
      inferior part of annulus fibrosus (superior-middle-inferior ratio 39:59:140, P <
      0.001). One hundred and eighty-one HIZs (76.1%) occurred at L4/5 and/or L5/S1.
      The prevalence of multi-segmental HIZ was 16.5%. Among the 33 patients with multi
      segmental HIZs, 24 exhibited HIZs in adjacent disks. The LBP rate of HIZ patients
      was significantly higher than that of patients who exhibited no HIZ (57.5 vs.
      47.8%, P < 0.05). There was no evidence for a correlation between LBP and spatial
      distribution of HIZ in disk (P > 0.05). The incidence of LBP was slightly higher
      when the HIZ disk level was lower or when there were HIZs exhibited in more
      disks; however, the difference was statistically insignificant (P > 0.05).
      CONCLUSIONS: High-intensity zones occurred frequently at lower segments, inferior
      part of annulus fibrosus, and single disk.

PMID- 22391869
TI  - Not your mother's old age: Baby Boomers at age 65.

PMID- 22391871
TI  - Time for my life now: early Boomer women's anticipation of volunteering in
      retirement.
AB  - PURPOSE: This study explored to what extent early Boomer women who work for pay
      will be interested in and committed to formal volunteering during retirement.
      METHOD: Data for this hermeneutic study were gathered through 2 in-depth
      conversational interviews of 19 English-speaking early Boomer women living in New
      Brunswick, Canada. RESULTS: Interpretive analysis of interview data revealed that
      for these early Boomer women, consideration of volunteering in retirement
      revolves around analyzing the perceived costs and benefits, setting specific
      criteria for involvement, and recognizing the societal impacts of their refusal
      to volunteer or their limitation of commitment. IMPLICATIONS: Although not
      generalizable, the results of this study suggest administrators planning to
      recruit and retain retired early Boomer women to volunteer should not assume
      participation at the same rate or with the same commitment as previous
      generations. New models of volunteer recruitment and deployment may need to be
      developed to meet the expectations of these women. These participants indicated
      that formal volunteering will be for personal, not altruistic reasons, on their
      own terms through direct service; they are not interested in the consuming
      commitments of board and committee work or fundraising. Volunteering must be
      meaningful, something about which they are passionate and on their own schedule.

PMID- 22391870
TI  - Baby Boomers in an active adult retirement community: comity interrupted.
AB  - PURPOSE OF THE STUDY: This article explores a clash between incoming Baby Boomers
      and older residents in an active adult retirement community (AARC). We examine
      issues of social identity and attitudes as these groups encounter each other.
      DESIGN AND METHODS: Data are drawn from a multiyear ethnographic study of social
      relations in senior housing. Research at this site included in-depth, open-ended
      interviews (47), field notes (25), and participant observation in the field (500
      hr). Research team biweekly discussions and Atlas.ti software program facilitated
      analysis. FINDINGS: We begin with a poignant incident that has continued to
      engender feelings of rejection by elders with each retelling and suggests the
      power and prevalence of ageism in this AARC. We identify three pervasive themes:
      (a) social identity and image matter, (b) significant cultural and attitudinal
      differences exist between Boomers and older residents, and (c) shared age matters
      less than shared interests. IMPLICATIONS: Our data clearly show the operation of
      ageism in this community and an equating of being old with being sick. The
      conflict between these two age cohorts suggests that cohort consciousness among
      Boomers carries elements of age denial, shared by the older old. It also
      challenges the Third Age concept as a generational phenomenon.

PMID- 22391872
TI  - Impact of voluntary accreditation on deficiency citations in U.S. nursing homes.
AB  - PURPOSE OF THE STUDY:  This study examines the association between nursing home
      accreditation and deficiency citations.  DESIGN AND METHODS:  Data originated
      from a web-based search of The Joint Commission (TJC) accreditation and On-line
      Survey Certification of Automated Records from 2002 to 2010. Deficiency citations
      were divided into 4 categories: resident behavior and facility practices, quality
      of life, quality of care, and the most severe citations. Data were analyzed
      through negative binomial regression, where the number of residents at risk for
      each measure was the exposure level for that measure.  RESULTS:  TJC-accredited
      nursing homes had fewer deficiency citations in all 4 deficiency categories
      examined. Comparing citations in the year of accreditation with the first year
      after accreditation, 3 of the 4 deficiency categories were significant. In
      comparing deficiency citations after 8 years of accreditation, all 4 categories
      of deficiencies were significant. In all cases, accreditation was associated with
      fewer deficiency citations.  IMPLICATIONS:  Our results indicate that TJC
      accredited nursing homes improve their quality immediately after accreditation
      and continue to maintain these improvements over the long-term. These findings
      support the need for further discussion and facilitation of voluntary
      accreditation in nursing homes.

PMID- 22391873
TI  - Health behaviors among Baby Boomer informal caregivers.
AB  - PURPOSE OF THE STUDY: This study examines health-risk behaviors among "Baby
      Boomer" caregivers and non-caregivers. DESIGN AND METHODS: Data from the 2009
      California Health Interview Survey of the state's non-institutionalized
      population provided individual-level, caregiving, and health behavior
      characteristics for 5,688 informal caregivers and 12,941 non-caregivers. Logistic
      regression models were estimated separately for four individual health-risk
      behaviors-smoking, sedentary behavior, and regular soda and fast-food consumption
      as well as a global health-risk measure. RESULTS: Controlling for psychological
      distress and personal characteristics and social resources such as age, gender,
      income and education, work and marital status, and neighborhood safety,
      caregivers had greater odds than non-caregivers of overall negative health
      behavior and of smoking and regular soda and fast-food consumption. We did not
      observe significant differences in odds of negative behavior related to stress
      for spousal caregivers and caregivers in the role for longer periods of time or
      those providing more hours of weekly care compared with other caregivers.
      IMPLICATIONS: Our study found evidence that Baby Boomer caregivers engage in poor
      health behaviors that are associated with exposure to caregiving. Baby Boomer
      caregivers may be at risk for certain behavioral factors that are associated with
      disability and chronic illness.

PMID- 22391875
TI  - Coordination chemistry in the solid state.

PMID- 22391874
TI  - Stabilised DNA secondary structures with increasing transcription localise
      hypermutable bases for somatic hypermutation in IGHV3-23.
AB  - Somatic hypermutation (SHM) mediated by activation-induced cytidine deaminase
      (AID) is a transcription-coupled mechanism most responsible for generating high
      affinity antibodies. An issue remaining enigmatic in SHM is how AID is
      preferentially targeted during transcription to hypermutable bases in its
      substrates (WRC motifs) on both DNA strands. AID targets only single stranded
      DNA. By modelling the dynamical behaviour of IGHV3-23 DNA, a commonly used human
      variable gene segment, we observed that hypermutable bases on the non-transcribed
      strand are paired whereas those on transcribed strand are mostly unpaired.
      Hypermutable bases (both paired and unpaired) are made accessible to AID in
      stabilised secondary structures formed with increasing transcription levels. This
      observation provides a rationale for the hypermutable bases on both the strands
      of DNA being targeted to a similar extent despite having differences in
      unpairedness. We propose that increasing transcription and RNAP II stalling
      resulting in the formation and stabilisation of stem-loop structures with AID
      hotspots in negatively supercoiled region can localise the hypermutable bases of
      both strands of DNA, to AID-mediated SHM.

PMID- 22391876
TI  - The effects of temozolomide delivered by prolonged intracerebral microinfusion
      against the rat brainstem GBM allograft model.
AB  - OBJECTIVE: Diffuse intrinsic brainstem gliomas are considered to be inoperable.
      We report our initial experience of temozolomide (TMZ) administration into
      brainstem by intracerebral (i.c.) microinfusion using a rat brainstem
      glioblastoma allograft model. METHODS: Forty-eight Fischer 344 female rats were
      used. In a feasibility study, various doses of i.c.-TMZ (1-10 mg) were
      administered into the brainstem using AlzetTM pumps in order to evaluate survival
      rates and neurotoxicity. For tumor implantation, rats received an injection of
      10(5) 9 L gliosarcoma cells. For local therapy, 5 days after inoculation, a total
      amount of 1 mg of TMZ or saline was administered into the brainstem at 1 MUl/h
      over 7 days (n = 8/group). For systemic therapy, rats were treated with an orally
      administered maximum daily dose of 50 mg/kg TMZ for 5 consecutive days. Survival
      time and neurological deficit were recorded as outcome parameters. RESULTS: In
      the neurotoxicity study, low dose TMZ (1 mg) was feasible to be administered into
      brainstem over 7 days without neurological deficit. Using high dose TMZ (5-10
      mg), marked neurotoxic effect was observed. In the brainstem tumor study,
      survival was significantly prolonged in low dose i.c.-TMZ group compared to
      control rats (median survival 23.5 versus 29.5 days; p < 0.01). Systemic therapy
      with maximal oral-TMZ dose resulted in longer survival time compared to low dose
      i.c.-TMZ group (median survival 33.5 versus 29.5 days; p < 0.01). CONCLUSIONS:
      i.c.-TMZ is feasible and effective against rat brainstem glioblastoma allograft.
      However, we could not show superior potential of i.c.-TMZ compared to oral-TMZ
      administration. Modification of TMZ infusion with systemic therapy warrants
      future investigations.

PMID- 22391877
TI  - Porous polysulfone coatings for enhanced drug delivery.
AB  - The synthesis of a porous polysulfone (PSU) coating for use in drug delivery
      applications is presented. PSU can serve as a functional surface coating for drug
      delivery vehicles, such as intraocular biomicrorobots. The coatings can be
      applied using spin coating or dip coating. The porosity is introduced by
      selectively dissolving calcium carbonate nanoparticles embedded in the bulk
      polymer. The network of pores thus formed increases by a factor of thirty the
      amount of Rhodamine B (model drug) that can be loaded and by a factor of fifteen
      the amount that can be released. The films do not affect cell viability and
      exhibit poor cell adhesion. The straightforward synthesis and predictability of
      porosity enables the tuning of the amount of drug that can be loaded.

PMID- 22391878
TI  - A fully microfabricated carbon nanotube three-electrode system on glass substrate
      for miniaturized electrochemical biosensors.
AB  - We present an integration process to fabricate single-walled carbon nanotube
      (SWCNT) three-electrode systems on glass substrate for electrochemical
      biosensors. Key issues involve optimization of the SWCNT working electrode to
      achieve high sensitivity, developing an optimal Ag/AgCl reference electrode with
      good stability, and process development to integrate these electrodes. Multiple
      spray coatings of the SWCNT film on glass substrate enabled easier integration of
      the SWCNT film into an electrochemical three-electrode system. O2 plasma etching
      and subsequent activation of spray-coated SWCNT films were needed to pattern and
      functionalize the SWCNT working electrode films without serious damage to the
      SWCNTs, and to remove organic residues. The microfabricated three-electrode
      systems were characterized by microscopic and spectroscopic techniques, and the
      electrochemical properties were investigated using cyclic voltammetry and chrono
      amperometry. The fully-integrated CNT three-electrode system showed an effective
      working electrode area about three times larger than its geometric surface area
      and an improved electrochemical activity for hydrogen peroxide decomposition.
      Finally, the effectiveness of miniaturized pf-SWCNT electrodes as biointerfaces
      was examined by applying them to immunosensors to detect Legionella(L)
      pneumophila, based on a direct sandwich enzyme-linked immunosorbent assay (ELISA)
      format with 3,3',5,5'-tetramethylbenzidine dihydrochloride/hydrogen
      peroxide(TMB/H2O2) as the substrate/mediator system. The lower detection limit of
      the pf-SWCNT-based immunosensors to L. pneumophila is about 1500 times lower than
      that of the standard ELISA assay.

PMID- 22391879
TI  - Multiplexed suspension array platform for high-throughput protein assays.
AB  - A multiplexed suspension array platform, based on SU8 disks patterned with
      machine-readable binary identification codes is presented. Multiple probe
      molecules, each attached to individual disks with different unique codes, provide
      multiplexed detection of targets in a small sample volume. The experimental
      system consists of a microfluidic chamber for arraying the particles in a manner
      suitable for high throughput imaging using a simple fluorescent microscope,
      together with custom software for automated code readout and analysis of assay
      response. The platform is demonstrated with a multiplexed antibody assay
      targeting 3 different human inflammatory cytokines. The suitability of the
      platform for other bio-analytical applications is discussed.

PMID- 22391880
TI  - Determination of the size distribution of blood microparticles directly in plasma
      using atomic force microscopy and microfluidics.
AB  - Microparticles, also known as microvesicles, found in blood plasma, urine, and
      most other body fluids, may serve as valuable biomarkers of diseases such as
      cardiovascular diseases, systemic inflammatory disease, thrombosis, and cancer.
      Unfortunately, the detection and quantification of microparticles are hampered by
      the microscopic size of these particles and their relatively low abundance in
      blood plasma. The use of a combination of microfluidics and atomic force
      microscopy to detect microparticles in blood plasma circumvents both problems. In
      this study, capture of a specific subset of microparticles directly from blood
      plasma on antibody-coated mica surface is demonstrated. The described method
      excludes isolation and washing steps to prepare microparticles, improves the
      detection sensitivity, and yields the size distribution of the captured
      particles. The majority of the captured particles have a size ranging from 30 to
      90 nm, which is in good agreement with prior results obtained with microparticles
      immediately isolated from fresh plasma. Furthermore, the qualitative shape of the
      size distribution of microparticles is shown not to be affected by high-speed
      centrifugation or the use of the microfluidic circuit, demonstrating the relative
      stable nature of microparticles ex vivo.

PMID- 22391881
TI  - Mesh-supported submicron parylene-C membranes for culturing retinal pigment
      epithelial cells.
AB  - In this work, a mesh-supported submicron parylene-C membrane (MSPM) is proposed
      as an artificial Bruch's membrane for the therapy of age-related macular
      degeneration (AMD). Any artificial Bruch's membrane must first satisfy two
      important requirements. First, it should be as permeable as healthy human Bruch's
      membrane to support nutrients transportation. Secondly, it should be able to
      support the adherence and proliferation of retinal pigment epithelial (RPE) cells
      with in vivo-like morphologies and functions. Although parylene-C is widely used
      as a barrier layer in many biomedical applications, it is found that parylene-C
      membranes with submicron thickness are semipermeable to macromolecules. We first
      measure the permeability of submicron parylene-C and find that 0.15-0.30 MUm
      parylene-C has similar permeability to healthy human Bruch's membranes. Blind
      well perfusion cell viability experiments further demonstrate that nutrients and
      macromolecules can diffuse across 0.30 MUm parylene-C to nourish the cells. A
      mesh-supported submicron parylene-C membrane (MSPM) structure is design to
      enhance the mechanical strength of the substrate. In vitro cells culture on the
      MSPM (with 0.30 MUm ultrathin parylene-C) shows that H9-RPE cells are able to
      adhere, proliferate, form epithelial monolayer with tight intracellular
      junctions, and become well-polarized with microvilli, which exhibit similar
      characteristics to RPE cells in vivo. These studies have demonstrated the
      potential of the MSPM as an artificial Bruch's membrane for RPE cell
      transplantation.

PMID- 22391882
TI  - Obesity is a strong determinant of hypertensive target organ damage in young-to
      middle-age patients.
AB  - OBJECTIVE: To examine the impact of overweight and obesity on development of
      target organ damage in the early stage of hypertension. SUBJECTS: Participants
      were 727 young-to-middle-age subjects screened for stage 1 hypertension and
      followed for 8 years. MEASUREMENTS: Ambulatory blood pressure (BP), albumin
      excretion rate and echocardiographic data were obtained at entry, every 5 years
      and/or before starting antihypertensive treatment. RESULTS: During the follow-up,
      hypertension needing treatment was developed by 54.7% of the subjects with normal
      weight, 66.6% of those with overweight and 73.0% of those with obesity (P<0.001).
      Kaplan-Meier curves showed that patients with obesity or overweight progressed to
      sustained hypertension earlier than those with normal weight (P<0.001). At study
      end, rate of organ damage was 10.7% in the normal weight, 16.4% in the overweight
      and 30.1% in the obese subjects (P<0.001). In a multivariable logistic regression
      analysis, overweight (P=0.008) and obesity (P<0.001) were significant predictors
      of final organ damage. Inclusion of changes in 24-h BP and body mass index, and
      of baseline organ damage did not virtually modify these associations (P=0.002 and
      <0.001, respectively). Obesity was a significant predictor of both left
      ventricular hypertrophy (P<0.001) and microalbuminuria (P=0.015) with an odds
      ratio (95% confidence interval) of 8.5 (2.7-26.8) and 3.5 (1.3-9.6),
      respectively. CONCLUSION: These data indicate that in hypertensive subjects
      obesity has deleterious effects on the cardiovascular system already at an early
      age. Preventive strategies addressed to achieve weight reduction should be
      implemented at a very early stage in young people with excess adiposity and high
      BP.

PMID- 22391883
TI  - Role of orexin receptors in obesity: from cellular to behavioral evidence.
AB  - The orexin peptides and their two receptors are involved in multiple
      physiological processes, including energy homeostasis, arousal, stress and
      reward. Higher signaling of the orexin peptides at the orexin receptors (OXR)
      protects against obesity, but it is less clear how their activation in different
      brain regions contributes to this behavioral output. This review summarizes the
      evidence available for a role of central OXR in energy homeostasis and their
      contribution to obesity. A detailed analysis of anatomical, cellular and
      behavioral evidence shows that modulation of energy homeostasis by the OXR is
      largely dependent upon anatomical and cellular context. It also shows that
      obesity resistance provided by activation of the OXR is distributed across
      multiple brain sites with site-specific actions. We suggest that understanding
      the role of the OXR in the development of obesity requires considering both
      specific mechanisms within brain regions and interactions of orexinergic input
      between multiple sites.

PMID- 22391884
TI  - Ethnic differentiation of copy number variation on chromosome 16p12.3 for
      association with obesity phenotypes in European and Chinese populations.
AB  - OBJECTIVE: Genomic copy number variations (CNVs) have been strongly implicated as
      important genetic factors for obesity. A recent genome-wide association study
      identified a novel variant, rs12444979, which is in high linkage disequilibrium
      with CNV 16p12.3, for association with obesity in Europeans. The aim of this
      study was to directly examine the relationship between the CNV 16p12.3 and
      obesity phenotypes, including body mass index (BMI) and body fat mass. SUBJECTS:
      Subjects were a multi-ethnic sample, including 2286 unrelated subjects from a
      European population and 1627 unrelated Han subjects from a Chinese population.
      Body fat mass was measured using dual energy X-ray absorptiometry. RESULTS: Using
      Affymetrix Genome-Wide Human SNP Array 6.0, we directly detected CNV 16p12.3,
      with the deletion frequency of 27.26 and 0.8% in the European and Chinese
      populations, respectively. We confirmed the significant association between this
      CNV and obesity (BMI: P=1.38 * 10(-2); body fat mass: P=2.13 * 10(-3)) in the
      European population. Less copy numbers were associated with lower BMI and body
      fat mass, and the effect size was estimated to be 0.62 (BMI) and 1.41 (body fat
      mass), respectively. However, for the Chinese population, we did not observe
      significant association signal, and the frequencies of this deletion CNV are
      quite different between the European and Chinese populations (P<0.001).
      CONCLUSION: Our findings first suggest that CNV 16p12.3 might be ethnic specific
      and cause ethnic phenotypic diversity, which may provide some new clues into the
      understanding of the genetic architecture of obesity.

PMID- 22391885
TI  - Variations in the obesity genes FTO, TMEM18 and NRXN3 influence the vulnerability
      of children to weight gain induced by short sleep duration.
AB  - OBJECTIVE: Shorter sleep duration predisposes to obesity, but the mechanisms
      whereby sleep deprivation affects body weight are poorly understood. We tested
      whether this association is modulated by the obesity genes FTO, TMEM18 and NRXN3.
      SUBJECTS: Body mass index (BMI), waist circumference, visceral fat (abdominal
      ultrasound), homeostasis model assessment for insulin resistance (HOMA-IR),
      systolic blood pressure (SBP) and sleep time per 24 h were assessed in 297
      asymptomatic children (151 boys, 146 girls; age range 5-9 years; BMI s.d. score
      range -2.0-4.0). Associations between sleep duration and the abovementioned
      outcomes were tested for three common single-nucleotide polymorphisms (SNPs),
      namely FTO (rs9939609), TMEM 18 (rs4854344) and NRXN3 (rs10146997), as well as
      for their combination. RESULTS: TT homozygotes (but not A(*) carriers) for the
      FTO SNP, exhibited nominal associations between decreasing sleep duration and
      increasing BMI, waist circumference, visceral fat and HOMA-IR (all P<0.05).
      Similar associations were observed in children with risk alleles (but not in
      those without risk alleles) for the TMEM18 and NRXN3 SNPs (P<0.05 to P<0.0001).
      The three SNPs had additive effects on the negative associations between sleep
      and, respectively, BMI (P<0.001), waist (P<0.005), visceral fat (P<0.001), HOMA
      IR (P=0.010) and SBP (P<0.0005). The combined effects on obesity measures and SBP
      remained significant after correction for multiple testing. On average, 2 h of
      sleep less per night was associated with an increase in BMI of 1.0 s.d. (95%
      confidence interval 0.5-1.6 s.d.) and with 8.0 cm (95% confidence interval 3.6
      12.2 cm) more waist circumference in genetically susceptible children.
      CONCLUSION: By age 7, common variations in FTO, TMEM18 and NRXN3 influence the
      vulnerability to metabolic complications of sleep deprivation. Further genetic
      studies are warranted to replicate these findings in other populations.

PMID- 22391886
TI  - In vitro insulin release from thermosensitive chitosan hydrogel.
AB  - Recently, great attention has been paid to in situ gel-forming chitosan/glycerol
      phosphate (chitosan/Gp) solution due to their good biodegradability and
      thermosensitivity. This in situ gel-forming system is injectable fluid that can
      be introduced into the body in a minimally invasive manner prior to solidifying
      within the desired tissue. At the present study, insulin release from chitosan/Gp
      solution has been investigated. Insulin in different concentrations was loaded in
      two formulations of chitosan/Gp solution and in vitro drug release was studied
      over a period of 3 weeks. Results indicated that the release of insulin from
      chitosan/Gp gel decreases by increasing in Gp salt and initial insulin
      concentration. Stability of released insulin was investigated by 8-anilino-1
      naphthalenesulfonate probe. Results proved that insulin have been released in its
      native form. Because of simple preparation and administration, prolonged release
      of insulin and stability of released insulin, this in situ gel-forming system
      could be used as a controlled release delivery system for insulin.

PMID- 22391887
TI  - Physicochemical properties of amorphous roxithromycin prepared by quench cooling
      of the melt or desolvation of a chloroform solvate.
AB  - Roxithromycin is a poorly soluble antibacterial drug. The aim of this study was
      to prepare and characterize an amorphous form of roxithromycin. The amorphous
      form was prepared by desolvation of its chloroform solvate, and by quench cooling
      a melt of the crystalline monohydrated solid. The X-ray powder diffraction
      pattern of the desolvated chloroform solvate was indistinguishable from that of
      the glass prepared by melting, which indicated that it was amorphous. The
      roxithromycin glass was determined to be a fragile glass, but due to its high
      Kauzmann temperature (approximately 8 degrees C), it should remain fairly stable
      upon refrigeration or even at room temperature. It was also determined that this
      glass remains stable in the presence of moisture with no indication of
      crystallization.

PMID- 22391888
TI  - Could hydrolysis of arsenic substituted DNA be prevented? Protection arises from
      stacking interactions.
AB  - Investigation of the hydrolysis of dinucleoside-arsenate-deoxyguanylyl-3',5'
      deoxyguanosine (dGAsdG(-)) reveals that base-stacking in DNA increases the
      resistance of As-DNA towards hydrolysis. Base-stacking raises the activation
      energy of hydrolysis. Hydrolysis of As-DNA is found to be endothermic. The
      hydrolysis stability of As-DNA should be higher than that estimated based on
      arsenate diester models.

PMID- 22391889
TI  - Interruption of glycosphingolipid synthesis enhances osteoarthritis development
      in mice.
AB  - OBJECTIVE: Glycosphingolipids (GSLs) are ubiquitous membrane components that
      modulate transmembrane signaling and mediate cell-to-cell and cell-to-matrix
      interactions. GSL expression is decreased in the articular cartilage of humans
      with osteoarthritis (OA). This study was undertaken to determine the functional
      role of GSLs in cartilage metabolism related to OA pathogenesis in mice. METHODS:
      We generated mice with knockout of the chondrocyte-specific Ugcg gene, which
      encodes an initial enzyme of major GSL synthesis, using the Cre/loxP system (Col2
      Ugcg(-/-)  mice). In vivo OA and in vitro cartilage degradation models were used
      to evaluate the effect of GSLs on the cartilage degradation process. RESULTS:
      Although Col2-Ugcg(-/-)  mice developed and grew normally, OA changes in these
      mice were dramatically enhanced with aging, through the overexpression of matrix
      metalloproteinase 13 and chondrocyte apoptosis, compared to their wild-type (WT)
      littermates. Col2-Ugcg(-/-)  mice showed more severe instability-induced
      pathologic OA in vivo and interleukin-1alpha (IL-1alpha)-induced cartilage
      degradation in vitro. IL-1alpha stimulation of chondrocytes from WT mice
      significantly increased Ugcg messenger RNA expression and up-regulated GSL
      metabolism. CONCLUSION: Our results indicate that GSL deficiency in mouse
      chondrocytes enhances the development of OA. However, this deficiency does not
      affect the development and organization of cartilage tissue in mice at a young
      age. These findings indicate that GSLs maintain cartilage molecular metabolism
      and prevent disease progression, although GSLs are not essential for
      chondrogenesis of progenitor and stem cells and cartilage development in young
      mice. GSL metabolism in the cartilage is a potential target for developing a
      novel treatment for OA.

PMID- 22391891
TI  - Competition-strength-dependent ground suppression in figure-ground perception.
AB  - Figure-ground segregation is modeled as inhibitory competition between objects
      that might be perceived on opposite sides of borders. The winner is the figure;
      the loser is suppressed, and its location is perceived as shapeless ground.
      Evidence of ground suppression would support inhibitory competition models and
      would contribute to explaining why grounds are shapeless near borders shared with
      figures, yet such evidence is scarce. We manipulated whether competition from
      potential objects on the ground side of figures was high (i.e., portions of
      familiar objects were potentially present there) or low (novel objects were
      potentially present). We predicted that greater competition would produce more
      ground suppression. The results of two experiments in which suppression was
      assessed via judgments of the orientation of target bars confirmed this
      prediction; a third experiment showed that ground suppression is short-lived. Our
      findings support inhibitory competition models of figure assignment, in
      particular, and models of visual perception entailing feedback, in general.

PMID- 22391890
TI  - Impact of phenylephrine administration on cerebral tissue oxygen saturation and
      blood volume is modulated by carbon dioxide in anaesthetized patients.
AB  - BACKGROUND: Multiple studies have shown that cerebral tissue oxygen saturation
      (Sct(O(2))) is decreased after phenylephrine treatment. We hypothesized that the
      negative impact of phenylephrine administration on Sct(O(2)) is affected by
      arterial blood carbon dioxide partial pressure (Pa(CO(2))) because CO(2) is a
      powerful modulator of cerebrovascular tone. METHODS: In 14 anaesthetized healthy
      patients, i.v. phenylephrine bolus was administered to increase the mean arterial
      pressure ~20-30% during hypocapnia, normocapnia, and hypercapnia. Sct(O(2)) and
      cerebral blood volume (CBV) were measured using frequency domain near-infrared
      spectroscopy, a quantitative technology. Data collection occurred before and
      after each treatment. RESULTS: Phenylephrine caused a significant decrease in
      Sct(O(2)) during hypocapnia [DeltaSct(O(2)) =-3.4 (1.5)%, P<0.001], normocapnia
      [DeltaSct(O(2)) =-2.4 (1.5)%, P<0.001], and hypercapnia [DeltaSct(O(2)) =-1.4
      (1.5)%, P<0.01]. Decreases in Sct(O(2)) were significantly different between
      hypocapnia, normocapnia, and hypercapnia (P<0.001). Phenylephrine also caused a
      significant decrease in CBV during hypocapnia (P<0.01), but not during
      normocapnia or hypercapnia. CONCLUSION: The negative impact of phenylephrine
      treatment on Sct(O(2)) and CBV is intensified during hypocapnia while blunted
      during hypercapnia.

PMID- 22391892
TI  - On the replication of Kristofferson's (1980) quantal timing for duration
      discrimination: some learning but no quanta and not much of a Weber constant.
AB  - This study revisited Kristofferson's (Perception & Psychophysics 27:300-306,
      1980) report showing that, with sufficient practice at interval discrimination,
      the relationship between timing variability and physical time is a step function
      in other words, that psychological time is quantized. Two participants completed
      260 sessions of a temporal discrimination task, 20 consecutive sessions for each
      of 13 base durations ranging from 100 to 1,480 ms. The data do not replicate
      Kristofferson's (Perception & Psychophysics 27:300-306, 1980) quantal finding,
      and it is argued that the effect Kristofferson reported may have been due to
      specific methodological decisions. Importantly, the data show (1) some limitation
      of Weber's law for time, even for the narrow range of the present investigation,
      and (2) that extensive training provides some modest benefit to temporal
      discrimination, mainly for longer intervals, and that this benefit primarily
      occurs in the first few sessions.

PMID- 22391893
TI  - Effects of parafoveal word length and orthographic features on initial fixation
      landing positions in reading.
AB  - Previous research has demonstrated that readers use word length and word boundary
      information in targeting saccades into upcoming words while reading. Previous
      studies have also revealed that the initial landing positions for fixations on
      words are affected by parafoveal processing. In the present study, we examined
      the effects of word length and orthographic legality on targeting saccades into
      parafoveal words. Long (8-9 letters) and short (4-5 letters) target words, which
      were matched on lexical frequency and initial letter trigram, were paired and
      embedded into identical sentence frames. The gaze-contingent boundary paradigm
      (Rayner, 1975) was used to manipulate the parafoveal information available to the
      reader before direct fixation on the target word. The parafoveal preview was
      either identical to the target word or was a visually similar nonword. The
      nonword previews contained orthographically legal or orthographically illegal
      initial letters. The results showed that orthographic preprocessing of the word
      to the right of fixation affected eye movement targeting, regardless of word
      length. Additionally, the lexical status of an upcoming saccade target in the
      parafovea generally did not influence preprocessing.

PMID- 22391894
TI  - Partial repetition costs persist in nonsearch compound tasks: evidence for
      multiple-weighting-systems hypothesis.
AB  - Search performance is sequence-dependent. A specific finding observed in compound
      search tasks consists of an interaction between cross-trial sequences (repetition
      vs. change) of the target-defining (primary) and response-defining (secondary)
      features: The effect of a target change is greater when the response stays the
      same than when the response changes. The present study tested whether this
      interaction arises from processes involved in target search or from later
      processes in compound tasks. Uncertainty about the upcoming target location-that
      is, the search component of compound tasks-was removed in different experiments,
      either by the use of exogenous spatial precues or by presenting only one, central
      item. Despite having removed the search component, we observed a robust
      interaction between target (primary) and response (secondary) feature sequences.
      These results suggest that this interaction originates from a processing stage
      concerned with discriminating the response feature of a single (selected) item,
      rather than from a search-related stage. Furthermore, the results support our
      multiple-weighting-systems hypothesis, according to which sequence effects in
      visual search tasks do not stem from a single, unitary mechanism; rather,
      multiple stages of processing on any given trial can lead to separate memory
      traces, which in turn have effects on different stages of processing on the
      subsequent trial.

PMID- 22391895
TI  - Enhanced Computer Modeling of Cardiac Action Potential Dynamics using
      Experimental Data-Based Feedback.
AB  - Mathematical models of cardiac action potential (AP) dynamics are useful for
      studying the formation of dynamically significant patterns such as alternans and
      conduction block. A closed-loop observer is an augmented version of a
      mathematical model, in which experimental data are supplied to the model through
      feedback. In this study, tools for observer analysis were applied to a two
      variable Karma model of AP dynamics. For a single-cell system, it was confirmed
      that membrane potential data could be used to reconstruct the system state, and
      that Luenberger feedback could stabilize the observer. Next an observer with a 1D
      geometry was tested with microelectrode membrane-potential data from a 2.1cm in
      vitro canine Purkinje fiber. It was shown that the observer produced more
      accurate AP duration (APD) estimates than the model by itself. These
      reconstructed quantities could be used to provide enhanced information to anti
      tachyarrhythmic stimulus protocols that depend on real-time measurements.

PMID- 22391896
TI  - Cautious backing for proposals to reduce red tape in farming.

PMID- 22391897
TI  - GALVmed awarded L31 million to scale-up its work on vaccines.

PMID- 22391898
TI  - Owners 'worryingly unprepared' for health problems in older pets.

PMID- 22391899
TI  - Geographical spread of UK cases of SBV 'within expectations'.

PMID- 22391901
TI  - Encouraging the profession's future leaders.

PMID- 22391902
TI  - Research aims to help vulnerable dog breeds.

PMID- 22391904
TI  - New veterinary physiotherapy association.

PMID- 22391905
TI  - Control or eradication? Costs and benefits in the case of PRRSV.

PMID- 22391906
TI  - Performing in the aid circus.

PMID- 22391907
TI  - Echinococcus risk from imported beavers.

PMID- 22391908
TI  - Honing basic consultation skills.

PMID- 22391909
TI  - Donating medicines to welfare projects.

PMID- 22391910
TI  - Use of suture materials in practice.

PMID- 22391911
TI  - Prevention of Schmallenberg virus.

PMID- 22391912
TI  - Heavyweight science.

PMID- 22391921
TI  - Quantum mechanical polar surface area.
AB  - A correlation has been established between the absorbed fraction of training-set
      molecules after oral administration in humans and the Quantum Mechanical Polar
      Surface Area (QMPSA). This correlation holds for the QMPSA calculated with
      structures where carboxyl groups are deprotonated. The correlation of the
      absorbed fraction and the QMPSA calculated on the neutral gas phase optimized
      structures is much less pronounced. This suggests that the absorption process is
      mainly determined by polar interactions of the drug molecules in water solution.
      Rules are given to derive the optimal polar/apolar ranges of the electrostatic
      potential.

PMID- 22391923
TI  - Primary amebic meningoencephalitis: a case report and literature review.
AB  - Primary amebic meningoencephalitis (PAM) is a rare but nearly always fatal
      disease caused by infection with Naegleria fowleri, a thermophilic, free-living
      ameba found in freshwater environments. Cases of N. fowleri infection have been
      reported from many of the southern-tier states in the United States, with Florida
      and Texas disproportionately represented among them. Primary amebic
      meningoencephalitis presents clinically in a fashion that may be
      indistinguishable from bacterial and viral meningitis. Unfortunately, because the
      disease is so rare, PAM is often excluded from the differential diagnosis of
      children with meningitis resulting in delayed diagnostic and therapeutic
      efforts.Pediatric acute care practitioners in emergency departments, general
      pediatric wards, and critical care units, especially those practicing in the
      southern United States, should be familiar with the risk factors for acquisition
      of PAM, its clinical presentation, and the fact that common empiric treatment of
      bacterial meningitis will not treat N. fowleri. Herein, we present the case of an
      adolescent who died of PAM and review the (a) epidemiology, (b) pathophysiology,
      (c) available diagnostic modalities, (d) treatment options, and (e) outcomes of
      patients treated for N. fowleri infection of the central nervous system.

PMID- 22391922
TI  - Synthesis and characterization of azolate gold(I) phosphane complexes as
      thioredoxin reductase inhibiting antitumor agents.
AB  - Following an increasing interest in the gold drug therapy field, nine new neutral
      azolate gold(I) phosphane compounds have been synthesized and tested as
      anticancer agents. The azolate ligands used in this study are pyrazolates and
      imidazolates substituted with deactivating groups such as trifluoromethyl, nitro
      or chloride moieties, whereas the phosphane co-ligand is the triphenylphosphane
      or the more hydrophilic TPA (TPA = 1,3,5-triazaphosphaadamantane). The studied
      gold(I) complexes are: (3,5-bis-trifluoromethyl-1H-pyrazolate-1-yl)
      triphenylphosphane-gold(I) (1), (3,5-dinitro-1H-pyrazolate-1-yl)
      triphenylphosphane-gold(I) (2), (4-nitro-1H-pyrazolate-1-yl)-triphenylphosphane
      gold(I) (5), (4,5-dichloro-1H-imidazolate-1-yl)-triphenylphosphane-gold(I) (7),
      with the related TPA complexes (3), (4), (6) and (8) and (1-benzyl-4,5-di-chloro
      2H-imidazolate-2-yl)-triphenylphosphane-gold(I) (9). The presence of deactivating
      groups on the azole rings improves the solubility of these complexes in polar
      media. Compounds 1-8 contain the N-Au-P environment, whilst compound 9 is the
      only one to contain a C-Au-P environment. Crystal structures for compounds 1 and
      2 have been obtained and discussed. Interestingly, the newly synthesized gold(I)
      compounds were found to possess a pronounced cytotoxic activity on several human
      cancer cells, some of which were endowed with cis-platin or multidrug resistance.
      In particular, among azolate gold(I) complexes, 1 and 2 proved to be the most
      promising derivatives eliciting an antiproliferative effect up to 70 times higher
      than cis-platin. Mechanistic experiments indicated that the inhibition of
      thioredoxin reductase (TrxR) might be involved in the pharmacodynamic behavior of
      these gold species.

PMID- 22391924
TI  - A case of Menetrier disease in a child.
AB  - Menetrier disease is a protein-losing gastroenteropathy often misdiagnosed in the
      pediatric population. The disease is characterized by hypoalbuminemia secondary
      to protein loss through the gastrointestinal mucosa and resultant peripheral
      edema. It is important for emergency department practitioners to consider this
      diagnosis in the differential diagnosis for edema and low albumin levels in
      pediatric patients. We present a case report of Menetrier disease in an edematous
      child and a brief review.

PMID- 22391925
TI  - Concomitant hypercalcemia and hyperammonemia associated with distal renal tubular
      acidosis.
AB  - We describe an infant with concomitant hypercalcemia and hyperammonemia
      associated with nonanion gap metabolic acidosis secondary to distal renal tubular
      acidosis (dRTA). The levels of both serum calcium and ammonia rapidly normalized
      with the correction of dehydration and metabolic acidosis. To the best of our
      knowledge, there has been only one previous case report of concomitant
      hypercalcemia and hyperammonemia associated with dRTA that has been reported in
      the literature. We describe the causes and emergent management of hypercalcemia
      and review the possible mechanisms of this rare association with dRTA.

PMID- 22391926
TI  - Retrieval of a rectal foreign body using enemas in a 13-year-old boy.
AB  - In adults, rectal foreign bodies are a well-described phenomenon. In the
      pediatric emergency department, however, insertion of foreign bodies into the
      rectum is a rarely seen condition. Herein, we discuss a case of a rectal foreign
      body in a 13-year-old boy and the modality of removal.

PMID- 22391927
TI  - A case of infantile star anise toxicity.
AB  - Chinese star anise (Illicium verum) is a popular herbal remedy for infantile
      colic. Contamination with a related species of Japanese star anise (Illicium
      anisatum) has been related to cases of toxicity in infants. We report the case of
      a 3-month-old infant girl who presented to the emergency department with signs
      and symptoms of toxicity after recent star anise ingestion. Her presentation is
      consistent with other reports of toxicity that include particular
      gastrointestinal and neurological findings. A discussion of the clinical aspects
      of star anise toxicity, differential diagnosis, and management follows.

PMID- 22391928
TI  - Altered mental status and hematemesis in a child with hypercalcemia.
AB  - Altered mental status in a child is a potentially life-threatening condition with
      a broad differential including vascular, toxin-mediated, infectious, metabolic,
      and traumatic causes. Hypercalcemia is a rare cause of altered mental status in
      children. We report a case of a 13-month-old boy with familial hypocalciuric
      hypercalcemia who presented to our emergency department with altered mental
      status and hematemesis. Familial hypocalciuric hypercalcemia is a rare cause of
      hypercalcemia that usually presents with asymptomatic hypercalcemia. This case
      illustrates the presentation of severe hypercalcemia and reviews the initial
      management and evaluation of hypercalcemia in children.

PMID- 22391929
TI  - Salter-harris type 2 fracture of the proximal phalanx of the thumb with a
      rotational deformity: a case report and review.
AB  - Hand fractures are the most common site of injury in the pediatric population.
      They commonly involve the epiphyseal growth plates, and their standard
      classification is that of Salter-Harris (SH). Rotational deformities after SH
      fractures are rarely reported in literature. However, only 5 degrees of
      angulation can cause evident rotational deformity. This could be seen clinically
      and reconfirmed with radiologic evaluation. Up to this date, there are only a few
      cases of SH fractures with rotational deformity that have been described. We
      present 2 cases of SH type 2 with evidence of rotational deformity, which were
      reduced under local anesthesia in the emergency department. A review of
      literature is performed. Thus, examination for rotational deformities in SH
      fractures should be kept in mind. A satisfactory closed reduction under local
      anesthesia can be obtained.

PMID- 22391930
TI  - Dexmedetomidine sedation: uses in pediatric procedural sedation outside the
      operating room.
AB  - As the field of pediatric procedural sedation continues to expand, so does the
      exploration of medications that have a role in such invasive and noninvasive
      procedures. One such medication that has emerged during the last decade is
      dexmedetomidine, a drug approved for use in the adult intensive care setting. Its
      role in pediatrics has varied in its use from sedation in ventilated children in
      the intensive care unit to treatment for emergence reactions from general
      anesthesia and in sedation needed for radiographic imaging studies,
      electroencephalography, and invasive procedures. This review article presents the
      pediatric studies that have been published thus far regarding dexmedetomidate in
      the nonventilated, spontaneously breathing patient and identifies those patients
      where the use of this agent may not be indicated.

PMID- 22391932
TI  - Intussusception: edematous ileocecal valve mimicking incomplete reduction.

PMID- 22391933
TI  - ECGs in the ED.

PMID- 22391934
TI  - A 16-year-old with recalcitrant seizures.

PMID- 22391935
TI  - Working memory demands modulate cognitive control in the Stroop paradigm.
AB  - One important task of cognitive control is to regulate behavior by resolving
      information processing conflicts. In the Stroop task, e.g., incongruent trials
      lead to conflict-related enhancements of cognitive control and to improved
      behavioral performance in subsequent trials. Several studies suggested that these
      cognitive control processes are functionally and anatomically related to working
      memory (WM) functions. The present study investigated this suggestion and tested
      whether these control processes are modulated by concurrent WM demands. For this
      purpose, we performed three experiments in which we combined different WM tasks
      with the Stroop paradigm and measured their effects on cognitive control. We
      found that high WM demands led to a suppression of conflict-triggered cognitive
      control, whereas our findings suggest that this suppression effect is rather due
      to WM updating than to maintenance demands. We explain our findings by assuming
      that WM processes interfere with conflict-triggered cognitive control, harming
      the efficiency of these control processes.

PMID- 22391936
TI  - 1-Hour plasma glucose in obese youth.
AB  - Adults with normal glucose tolerance (NGT) but exaggerated plasma glucose
      excursion at 1 h (1HPG) following the oral glucose tolerance test (OGTT) have
      significantly higher risk of developing impaired glucose tolerance (IGT) or
      diabetes. Aim of the study will be to characterize the metabolic phenotype of NGT
      obese youth according to values of 1HPG. To accomplish this aim, obese patients
      (N = 1,454; 761 men; 79 IGT; BMI z-score 2.56 +/- 0.16 SDS; age 11 +/- 0.7 years)
      from two data sets were analyzed. In all patients, empirical parameters of
      insulin metabolism were calculated in fasting condition and following an OGTT
      (1.75 mg of glucose per kilogram/body weight). Receiver-operating characteristic
      (ROC) analysis was performed in the first group (training set, N = 920) to
      establish the cutoff value of 1HPG best identifying IGT. The second set
      (validation set, N = 534) served to verify the goodness of the model and the
      identified cutoff values. 1HPG >= 132.5 mg/dl identified IGT with 80.8%
      sensitivity and 74.3% specificity in the training set (AUC 0.855, 95% CI 0.808
      0.902, p < 0.0001), and 70.3% sensitivity and 80% specificity in the validation
      set (AUC 0.81, 95% CI 0.713-0.907, p < 0.0001), respectively. NGT patients with
      1HPG >= 132.5 mg/dl had a metabolic phenotype (triglycerides, insulin action, and
      secretion) that was in between those of NGT patients with 1HPG below the
      threshold and IGT patients (p < 0.0001 for all the comparisons). 1HPG >= 132.5
      mg/dl seems to be associated with increased metabolic risk in obese youth,
      identifying patients with lower insulin sensitivity, early secretion, and higher
      total insulin secretion than in obese mates with lower 1HPG.

PMID- 22391937
TI  - High meat consumption is associated with type 1 diabetes mellitus in a Sardinian
      case-control study.
AB  - The large worldwide variation in type 1 diabetes incidence and increasing
      incidence over time points toward important environmental risk factors. Among
      them, nutrition plays an important role. The objective was to investigate the
      relationship between type 1 diabetes and nutritional factors in pregnancy and
      early in life. We carried out, using semi-quantitative food frequency
      questionnaires, a retrospective case-control study in 298 children of 0-15 years
      old, 145 of which were affected by type 1 diabetes. The diet of all children and
      of their mothers during pregnancy and lactation was assessed. In children, a
      statistically significant dose-response association between type 1 diabetes and
      the amount of meat consumption was found while no other nutritional factors were
      associated with the disease. High meat consumption seems to be an important early
      in life cofactor for type 1 diabetes development, although these findings need to
      be confirmed in wider prospective follow-up studies. 

PMID- 22391938
TI  - Chemical reaction networks as a model to describe UVC- and radiolytically-induced
      reactions of simple compounds.
AB  - When a chemical system is submitted to high energy sources (UV, ionizing
      radiation, plasma sparks, etc.), as is expected to be the case of prebiotic
      chemistry studies, a plethora of reactive intermediates could form. If oxygen is
      present in excess, carbon dioxide and water are the major products. More
      interesting is the case of reducing conditions where synthetic pathways are also
      possible. This article examines the theoretical modeling of such systems with
      random-generated chemical networks. Four types of random-generated chemical
      networks were considered that originated from a combination of two connection
      topologies (viz., Poisson and scale-free) with reversible and irreversible
      chemical reactions. The results were analyzed taking into account the number of
      the most abundant products required for reaching 50% of the total number of moles
      of compounds at equilibrium, as this may be related to an actual problem of
      complex mixture analysis. The model accounts for multi-component reaction systems
      with no a priori knowledge of reacting species and the intermediates involved if
      system components are sufficiently interconnected. The approach taken is relevant
      to an earlier study on reactions that may have occurred in prebiotic systems
      where only a few compounds were detected. A validation of the model was attained
      on the basis of results of UVC and radiolytic reactions of prebiotic mixtures of
      low molecular weight compounds likely present on the primeval Earth. 

PMID- 22391939
TI  - Glucose metabolism in patients with subclinical Cushing's syndrome.
AB  - This clinical review will summarize the available data regarding the effect of
      either physiological or increased glucocorticoid concentrations on glucose
      metabolism and insulin-sensitivity, in order to clarify the role, if any, of
      subclinical Cushing's syndrome (SCS), a status of altered hypothalamic-pituitary
      adrenal axis secretion in the absence of the classical signs or symptoms of overt
      cortisol excess, in patients with adrenal incidentalomas (AI) and diabetes
      mellitus type 2. Focusing on patients with SCS associated to AI, while there is
      convincing evidence in the literature that even a mild hyper cortisolemia is
      associated with alterations of glucose metabolism, evidence is insufficient to
      conclude that the simple correction of chronic, even mild, hypercortisolism can
      completely revert metabolic, mainly glycemic alterations. At the same time,
      considering the variability of the prevalence of Cushing's syndrome in patients
      with diabetes mellitus type 2 reported in the literature, no agreement does exist
      whether screening for CS can be useful and recommended in those patients.

PMID- 22391940
TI  - Changes in serum 25-hydroxyvitamin D and cholecalciferol after one whole-body
      exposure in a commercial tanning bed: a randomized study.
AB  - We wanted to evaluate the cutaneous synthesis of 25OHD and cholecalciferol after
      one whole-body exposure to ultraviolet radiation type B (UVB) in a randomized
      setup. Healthy volunteers were randomized to one whole-body exposure in a
      commercial tanning bed with UVB emission (UVB/UVA ratio 1.8-2.0%) or an identical
      placebo tanning bed without UVB. The output in the 280-320 nm range was 450
      uW/cm2. Blood samples were analyzed for 25OHD and cholecalciferol at baseline and
      during 7 days after treatment. We included 20 volunteers, 11 to UVB and 9 to
      placebo treatment. During the first 6 h, no significant differences in 25OHD
      between the groups were found. At the end of the study, we found a mean increase
      of 25OHD in the UVB group of 4.5 nmol/l (SD 7 nmol/l) compared to a decline of 
      1.2 nmol/l (SD 7 nmol/l) in the placebo group (p = 0.1). A linear mixed model
      yielded an increase of 25OHD in the UVB group of 1.0 nmol/l per 24 h (p < 0.01).
      For cholecalciferol, we found a near significant increase of 1 pmol/l per hour in
      the UVB group compared to the placebo group during the first 6 h (p = 0.052). One
      tanning bed session had significant, but modest impact on the level of 25OHD
      during 7 days after exposure to UVB.

PMID- 22391942
TI  - Volar dislocation of second, third, and fourth carpometacarpal joints: a rare and
      easily missed diagnosis.
AB  - Volar carpometacarpal dislocation is a rare form of hand injury that can be
      easily missed without applying a high level of suspicion and performing a
      meticulous examination. In this case report, we present a rare case of compound
      volar dislocation of the second, third, and fourth carpometacarpal joints in a 40
      year-old male. This was managed by closed reduction and the use of a mini
      external fixator. The patient regained a good range of motion in 6 weeks with no
      pain. It is important to diagnose and treat this injury in order to avoid the
      considerable morbidity associated with this condition.

PMID- 22391941
TI  - Meta-analysis of association studies between five candidate genes and type 2
      diabetes in Chinese Han population.
AB  - The multiple small-scale association studies of candidate genes for type 2
      diabetes mellitus in the Chinese Han population have shown inconsistent results.
      Here, we performed a meta-analysis to evaluate the contribution of five candidate
      genes to the pathogenesis of type 2 diabetes in the Chinese Han population. We
      searched for relevant published papers and used STATA v.11.0 to perform a meta
      analysis on six single-nucleotide polymorphisms in five genes-ADIPOQ-rs2241766
      (SNP45) and -rs1501299 (SNP276), ADRB3-rs4994 (Trp64Arg), CAPN10-rs3792267
      (SNP43), ENPP1-rs1044498 (K121Q), and PPARGC1A-rs8192678 (Gly482Ser)-in the
      Chinese Han population under an additive genetic model. The pooled odds ratios
      (95% confidence intervals and P-values) were 0.71 (0.60-0.83; P < 0.001) for
      ADIPOQ-rs2241766, 0.79 (0.64-0.97; P = 0.027) for ADIPOQ-rs1501299, 1.27 (1.07
      1.51; P = 0.006) for ADRB3-rs4994, 0.79 (0.57-1.10; P = 0.163) for CAPN10
      rs3792267, 1.41 (1.13-1.76; P = 0.003) for ENPP1-rs1044498, and 1.54 (1.34-1.81;
      P < 0.001) for PPARGC1A-rs8192678. There was high heterogeneity for ADIPOQ
      rs2241766, ADIPOQ-rs1501299, and CAPN10-rs3792267 (I2 = 74.9, 69.4, and 75.8%,
      respectively), but not for ADRB3-rs4994, ENPP1-rs1044498, and PPARGC1A-rs8192678
      (I2 = 0.0, 43.4, and 23.3%, respectively). Under an additive genetic model, the C
      allele of ADRB3-rs4994, the C allele of ENPP1-rs1044498, and the A allele of
      PPARGC1A-rs8192678 increase the risk of type 2 diabetes in the Chinese Han
      population.

PMID- 22391943
TI  - Combined pubic rami and sacral osteoporotic fractures: a prospective study.
AB  - BACKGROUND: Pelvic osteoporotic fractures (POFs) are often associated with
      considerable morbidity and mortality mainly as a result of infections and
      cardiovascular events. Patients usually need prolonged institutionalization,
      rehabilitation, and follow-up, with a high rate of dependency and cost. The most
      common sites of POFs include the pubic rami, sacrum, ilium, and acetabulum.
      Combined pubic rami (PROFs) and sacral osteoporotic fractures (SOFs) have been
      reported, mostly in retrospective studies, describing the mechanism of injury and
      incidence. The aim of this study was to evaluate the association between PROFs
      and SOFs and to assess the effect of combined PROFs and SOFs on patients'
      mobility, discharge destination, and length of stay. MATERIALS AND METHODS: We
      prospectively studied 67 patients with low-impact PROFs and/or SOFs. There were
      54 (80.4%) female and 13 (19.6%) male patients, and the average age was 87.5
      (range 65-96) years. All patients were assessed by the fracture liaison service.
      Patients had magnetic resonance imaging or bone scan when there was history of
      low back pain following the injury or lumbosacral tenderness on clinical
      examination. RESULTS: The mean length of stay for all patients was 45 (+/- 35)
      days. Mortality rate was 10.4%. A significant relationship was found between low
      back pain and a positive finding of sacral fracture. Patients with combined PROFs
      and SOFs showed significantly longer length of stay than those with isolated
      PROFs. CONCLUSIONS: The presence of low back pain and tenderness in patients who
      had low-impact pelvic injuries was highly suggestive of the presence of an
      associated SOF. There was a high association between sacral and PROFs. The length
      of stay of patients with PROFs associated with sacral osteoporotic fractures was
      significantly longer than that of patients with PROFs only. Therefore, we
      recommend considering the high association between SOFs and PROFs in planning the
      management and rehabilitation of patients with POFs.

PMID- 22391944
TI  - Inflation osteoplasty: in vitro evaluation of a new technique for reducing
      depressed intra-articular fractures of the tibial plateau and distal radius.
AB  - BACKGROUND: Anatomic reduction of intra-articular fractures of the tibial plateau
      and distal radius can be difficult to achieve. Treatment goals are centered on
      restoring the native anatomy and articular congruency. Several surgeons in the
      USA have begun using an inflatable bone tamp to reduce these fracture patterns.
      The concept is built on the success of the tamp in kyphoplasty of the spine, but
      it has yet to be tested in the lab for use in the extremities. We performed an
      investigation into the safety and efficacy of using an inflatable bone tamp for
      intra-articular fracture reduction of the tibial plateau and distal radius.
      MATERIALS AND METHODS: Paired cadaveric specimens were obtained for a total of
      six proximal tibias and six distal radii. Intra-articular depression-type
      fractures were created in all specimens. The inflatable bone tamp was then used
      to reduce the depression. For comparison, the tibias were fractured on the medial
      and lateral side and a conventional metal tamp was used on the contralateral side
      of the balloon. Fine-cut micro-computed tomography (CT) scans were performed on
      all intact specimens, which were then fractured, and again after fracture
      reduction. CT data was used to measure the amount of restoration of the normal
      anatomy and to compare the effectiveness of the balloon to conventional methods.
      RESULTS: The inflatable bone tamp was equivalent to conventional methods in
      large, minimally displaced fracture fragments and proved superior when
      comminution was present at the articular surface. No instances of overreduction
      or penetration into the joint were encountered with the balloon, whereas this was
      a common occurrence with conventional metal tamps. The inflatable tamp was
      successful in reducing all distal radius fractures without complication.
      CONCLUSION: Anatomic reduction of impacted articular fractures should be the goal
      of any treating surgeon. In our cadaveric models, we have shown the inflatable
      bone tamp to be safe and effective in reducing depressed articular fractures
      around the tibial plateau and distal radius. The balloon offers the advantage of
      being minimally invasive and creating a symmetric, contained defect to hold bone
      filler for subchondral support.

PMID- 22391945
TI  - Mechanical behaviour and rupture of normal and pathological human ascending
      aortic wall.
AB  - The mechanical properties of aortic wall, both healthy and pathological, are
      needed in order to develop and improve diagnostic and interventional criteria,
      and for the development of mechanical models to assess arterial integrity. This
      study focuses on the mechanical behaviour and rupture conditions of the human
      ascending aorta and its relationship with age and pathologies. Fresh ascending
      aortic specimens harvested from 23 healthy donors, 12 patients with bicuspid
      aortic valve (BAV) and 14 with aneurysm were tensile-tested in vitro under
      physiological conditions. Tensile strength, stretch at failure and elbow stress
      were measured. The obtained results showed that age causes a major reduction in
      the mechanical parameters of healthy ascending aortic tissue, and that no
      significant differences are found between the mechanical strength of aneurysmal
      or BAV aortic specimens and the corresponding age-matched control group. The
      physiological level of the stress in the circumferential direction was also
      computed to assess the physiological operation range of healthy and diseased
      ascending aortas. The mean physiological wall stress acting on pathologic aortas
      was found to be far from rupture, with factors of safety (defined as the ratio of
      tensile strength to the mean wall stress) larger than six. In contrast, the
      physiological operation of pathologic vessels lays in the stiff part of the
      response curve, losing part of its function of damping the pressure waves from
      the heart.

PMID- 22391946
TI  - Safety of multi-channel stimulation implants: a single blocking capacitor per
      channel is not sufficient after single-fault failure.
AB  - One reason given for placing capacitors in series with stimulation electrodes is
      that they prevent direct current flow and therefore tissue damage under fault
      conditions. We show that this is not true for multiplexed multi-channel
      stimulators with one capacitor per channel. A test bench of two stimulation
      channels, two stimulation tripoles and a saline bath was used to measure the
      direct current flowing through the electrodes under two different single fault
      conditions. The electrodes were passively discharged between stimulation pulses.
      For the particular condition used (16 mA, 1 ms stimulation pulse at 20 Hz with
      electrodes placed 5 cm apart), the current ranged from 38 to 326 MUA depending on
      the type of fault. The variation of the fault current with time, stimulation
      amplitude, stimulation frequency and distance between the electrodes is given.
      Possible additional methods to improve safety are discussed.

PMID- 22391947
TI  - Dual stimuli-responsive dendritic-linear block copolymers.
AB  - Dendritic-linear block copolymers that have pH responsive poly(benzyl ether)
      dendrons and temperature responsive PiPrOx chains have been designed by copper
      mediated click reactions. These copolymers exhibit sharp thermal transitions with
      a wide range of pH-dependent thermal transition temperatures.

PMID- 22391948
TI  - Ghrelin contributes to derangements of glucose metabolism induced by rapamycin in
      mice.
AB  - AIMS/HYPOTHESIS: Rapamycin impairs glucose tolerance and insulin sensitivity. Our
      previous study demonstrated that rapamycin significantly increases the production
      of gastric ghrelin, which is critical in the regulation of glucose metabolism.
      Here, we investigated whether ghrelin contributes to derangements of glucose
      metabolism induced by rapamycin. METHODS: The effects of rapamycin on glucose
      metabolism were examined in mice receiving ghrelin receptor antagonist or with
      Ghsr1a gene knockout. Changes in GLUT4, c-Jun N-terminal kinase (JNK) and
      phosphorylated ribosomal protein S6 (pS6) were investigated by immunofluorescent
      staining or western blotting. Related hormones were detected by radioimmunoassay
      kits. RESULTS: Rapamycin impaired glucose metabolism and insulin sensitivity not
      only in normal C57BL/6J mice but also in both obese mice induced by a high fat
      diet and db/db mice. This was accompanied by elevation of plasma acylated
      ghrelin. Rapamycin significantly increased the levels of plasma acylated ghrelin
      in normal C57BL/6J mice, high-fat-diet-induced obese mice and db/db mice.
      Elevation in plasma acylated ghrelin and derangements of glucose metabolism upon
      administration of rapamycin were significantly correlated. The deterioration in
      glucose homeostasis induced by rapamycin was blocked by D: -Lys3-GHRP-6, a
      ghrelin receptor antagonist, or by deletion of the Ghsr1a gene. Ghrelin receptor
      antagonism and Ghsr1a knockout blocked the upregulation of JNK activity and
      downregulation of GLUT4 levels and translocation in the gastrocnemius muscle
      induced by rapamycin. CONCLUSIONS/INTERPRETATION: The current study demonstrates
      that ghrelin contributes to derangements of glucose metabolism induced by
      rapamycin via altering the content and translocation of GLUT4 in muscles.

PMID- 22391950
TI  - Exercise in type 2 diabetes: to resist or to endure?
AB  - There is now evidence that a single bout of endurance (aerobic) or resistance
      exercise reduces 24 h post-exercise subcutaneous glucose profiles to the same
      extent in insulin-resistant humans with or without type 2 diabetes. However, it
      remains to be determined which group would benefit most from specific exercise
      protocols, particularly with regard to long-term glycaemic control. Acute aerobic
      exercise first accelerates translocation of myocellular glucose transporters via
      AMP-activated protein kinase, calcium release and mitogen-activated protein
      kinase, but also improves insulin-dependent glucose transport/phosphorylation via
      distal components of insulin signalling (phosphoinositide-dependent kinase 1,
      TBC1 domain family, members 1 and 4, Rac1, protein kinase C). Post-exercise
      effects involve peroxisome-proliferator activated receptor-gamma coactivator
      1alpha and lead to ATP synthesis, which may be modulated by variants in genes
      such as NDUFB6. While mechanisms of acute resistance-type exercise are less
      clear, chronic resistance training activates the mammalian target of
      rapamycin/serine kinase 6 pathway, ultimately increasing protein synthesis and
      muscle mass. Over the long term, adherence to rather than differences in
      metabolic variables between specific modes of regular exercise might ultimately
      determine their efficacy. Taken together, studies are now needed to address the
      variability of individual responses to long-term resistance and endurance
      training in real life.

PMID- 22391949
TI  - Serine/threonine protein kinase 25 (STK25): a novel negative regulator of lipid
      and glucose metabolism in rodent and human skeletal muscle.
AB  - AIMS/HYPOTHESIS: This study investigates the role of serine/threonine protein
      kinase 25 (STK25), a member of the sterile 20 (STE20) superfamily of kinases, in
      the regulation of skeletal muscle metabolism. METHODS: The effect of depleting
      STK25 in muscle cells was studied by reducing the mRNA and protein content of
      this target in the rat myoblast cell line L6 by small interfering (si)RNA. The
      changes in the mRNA and protein levels of several members of the fatty acid
      oxidative and glucose metabolic pathways were measured by quantitative real-time
      (qRT)-PCR and western blot. The rate of palmitate oxidation and glucose uptake
      was measured after transfection with siRNA for Stk25. Expression of STK25 was
      also evaluated in skeletal muscle biopsies from 41 white Europid men and women
      with normal and impaired glucose tolerance and type 2 diabetes using qRT-PCR.
      RESULTS: We demonstrate that partial depletion of STK25 increases the expression
      of uncoupling protein 3 (Ucp3), accompanied by increased lipid oxidation, in
      myoblasts. In addition, a reduced level of STK25 enhances the expression of
      Slc2a1 (also known as Glut1), Slc2a4 (also known as Glut4) and hexokinase 2, and
      correspondingly, improves insulin-stimulated glucose uptake in muscle cells.
      Consistent with these results, significantly higher STK25 levels were observed in
      the skeletal muscle of type 2 diabetic patients, compared with individuals with
      normal glucose tolerance. CONCLUSIONS/INTERPRETATION: This is the first study
      indicating a possible role for STK25 in the regulation of glucose and lipid
      metabolism in L6 myoblasts. This kinase appears to be an interesting new mediator
      to be evaluated for therapeutic intervention in type 2 diabetes and related
      complications, as controlled increase in lipid oxidation and insulin-stimulated
      glucose uptake in skeletal muscle is favourable and can restore energy balance in
      metabolically compromised states.

PMID- 22391951
TI  - A new approach on the gastric absorption of anthocyanins.
AB  - The bioavailability of anthocyanins is the most difficult one to assess amongst
      all flavonoid compounds as a result of their occurrence under different
      structures in equilibrium depending on pH. Due to their rapid appearance in
      plasma, the absorption of anthocyanins is likely to occur at the gastric level.
      Further investigations of the mechanisms by which anthocyanins are absorbed are
      limited by the lack of testable gastric epithelial cell models that form
      functional barriers. The methods available to evaluate the absorption of drugs at
      the gastric level make use of isolated gastric epithelial cells, which is both
      time and labour consuming. In the present study, a biologically relevant in vitro
      model of moderately differentiated adenocarcinoma stomach cells (MKN-28) was used
      as gastric barrier. The transepithelial electrical resistance (TEER) of MKN-28
      cell monolayers was evaluated at pH values that cover the physiologic range of
      the stomach, ensuring the integrity of the cell monolayer . The
      immunofluorescence assay attested the localization of occludins at the cellular
      margins, which is associated with a non-disrupted membrane. Anthocyanins were
      found to cross MKN-28 cells in a time dependent manner and probably via a
      saturable transport mechanism.

PMID- 22391952
TI  - Muscle density in rheumatoid arthritis: associations with disease features and
      functional outcomes.
AB  - OBJECTIVE: To explore the associations between measures of body composition
      derived from computed tomography (CT) of the thigh and functional outcomes in
      patients with rheumatoid arthritis (RA). METHODS: Patients with RA underwent
      bilateral midfemoral quantitative CT for measurement of thigh fat area (TFA),
      thigh muscle area (TMA), and thigh muscle density (TMD). The associations of
      thigh-composition measures with disability and physical performance, as measured
      with the Health Assessment Questionnaire (HAQ), the Valued Life Activities
      (VLAs), and the Short Physical Performance Battery (SPPB) instruments, were
      explored in the total cohort and in the cohort subgrouped by sex, controlling for
      pertinent demographic, lifestyle, and RA disease and treatment covariates.
      RESULTS: A total of 152 RA patients were studied. Among the potential
      determinants of TMD, older age, longer duration of sedentary activity, longer
      duration of RA, higher tender joint count, higher serum interleukin-6 levels, use
      of glucocorticoids, and nonuse of hydroxychloroquine were all significantly
      associated with lower TMD in multivariable models. RA characteristics accounted
      for 63% of the explainable variability in TMD. When comodeled, higher TFA and
      lower TMD, but not lower TMA, were significantly and independently associated
      with higher HAQ scores, lower Short Form 36 health survey physical functioning
      scores, lower composite SPPB scores, and a greater proportion of affected
      obligatory VLAs. CONCLUSION: Thigh CT-derived measures of body composition,
      particularly fat area and muscle density, were strongly associated with
      disability and physical performance in RA patients, with RA disease features as
      potential determinants. Efforts to reduce fat and improve muscle quality may
      reduce disability in this population with impaired physical functioning.

PMID- 22391953
TI  - Context change and retrieval difficulty in the list-before-last paradigm.
AB  - Using the "list-before-last" paradigm (Jang & Huber, Journal of Experimental
      Psychology: Learning, Memory, and Cognition, 34, 112-127, 2008; Shiffrin,
      Science, 168, 1601-1603, 1970), we examined whether the difficulty involved in
      retrieving a previously studied list affects the recall of the current list.
      Participants studied three lists (L1, L2, and L3), and between L2 and L3 study
      they either engaged in retrieval of L1 or solved math problems for the same
      duration of time. After L3 encoding, all participants recalled L2. We examined
      accurate recall of L2, intrusions from L3, and also the first-response function
      from L2 across all four experiments. In Experiments 1 and 2, retrieval difficulty
      was manipulated by presenting participants with variable numbers of letter cues
      for the L1 words, with some participants receiving more cues than others. In
      Experiment 1, L1 and L2 words shared the first two letters in common to create
      potential item interference, whereas in Experiment 2, they did not share common
      cues. In Experiments 3 and 4, we manipulated retrieval difficulty using a delay
      manipulation-L1 was encoded 1, 24, or 72 h prior to the session during which L2
      and L3 were encoded. In Experiment 3, L1 retrieval involved a cued recall test,
      whereas in Experiment 4, it involved a free recall test. The results of all of
      these experiments showed that, as compared to solving math problems, retrieving
      L1 led to forgetting of L2, reduced intrusions from L3, and reduced first
      response functions from L2. However, all of the dependent measures were invariant
      across the various manipulations of retrieval difficulty. We discuss the results
      in terms of the context-change interpretation of prior-list retrieval.

PMID- 22391954
TI  - Examining the relationship between physician and facility level-of-service coding
      in outpatient wound centers: results of a multicenter study  .
AB  - The evaluation and management (E/M) services for the physician and the hospital
      based outpatient center ("facility") are calculated using different federal
      regulations. In addition, patients visiting outpatient wound care centers require
      different levels of care from the physician than the facility. The purpose of
      this study was to analyze and compare physician and facility E/M level-of-service
      coding using the electronic wound registry records from three geographically
      diverse, hospital-based outpatient wound centers. De-identified data on 9,985
      patient visit level-of-service codes were prospectively collected using an
      electronic health record (EHR) system that internally and automatically audits
      the chart and calculates the physician and the facility E/M level of service
      based on the documentation present in the chart. Correlations were calculated
      using Kendall's tau b/Goodman-Kruskal gamma statistics. Correlations were weak
      between facility and physician E/M level-of-service codes, varying from 0.084 to
      0.179 for follow-up and from 0.066 to 0.354 for initial visits. Although facility
      E/M levels of service followed a normal distribution, physician E/M visits were
      heavily skewed toward higher levels of care (3 to 5). These findings confirm
      that, especially during the initial visit, patients presenting at outpatient
      wound centers require different levels of care from the physician than from the
      facility. The finding that initial physician level of service coding was higher
      than facility E/M levels of service for both initial and follow-up visits is not
      unexpected, considering the high number of comorbidities in many wound patients
      and the general risk of their presenting problems.

PMID- 22391955
TI  - Using high-voltage electrical stimulation in the treatment of recalcitrant
      pressure ulcers: results of a randomized, controlled clinical study .
AB  - The use of electrical stimulation has been studied in a variety of wounds
      emphasizing different variables with regard to provision of therapy. The purpose
      of this prospective, randomized, controlled clinical study was to evaluate the
      effect of high-voltage electrical stimulation (HVES) on nonhealing, lower
      extremity, Stage II and Stage III pressure ulcers. Patients admitted for care and
      eligible to participate in the study received standard supportive care and
      topical treatments covered with wet-to-moist dressings. Patients assigned to the
      treatment arm of the study also received HVES (100 V; 100 MUs; 100 Hz)
      continuously for 50 minutes once daily, five times per week. Patients were
      followed until healing for a maximum of 6 weeks. Wound tracings and measurements
      were obtained weekly. Over a 4-year period, 26 patients were enrolled in the
      treatment and 24 in the control group. Ulcers had existed for an average of 3.17
      and 2.83 months in the treatment and control groups, respectively. Most were
      classified as Stage II (17 in the treatment and 16 in the control group) with an
      average baseline size of 4.54 cm2 and 3.97 cm2, respectively. Wound areas and
      linear measurements decreased significantly in both groups (P <0.05), but
      increases in granulation tissue were significant in the treatment group only (P =
      0.006). Wound area, linear measurement, wound volume, and granulation tissue
      changes were statistically significantly greater in the treatment than in the
      control group starting in the second week of treatment. Week 6 surface area
      change was 88.9% (SD 14) in the treatment and 44.4% (SD 63.1) in the control
      group (P = 0.00003). Correlation coefficients between changes in wound surface
      area, longest length, and longest width were R = 0.96 and R = 0.98 in the
      treatment and R = 0.94 and R = 0.89 in the control group. HVES improved the
      healing rate of recalcitrant Stage II and Stage III pressure ulcers. Research to
      compare the effectiveness of using cathodic and anodal stimulation combined or
      alone and to determine the optimal duration of these two types of electrical
      stimulation is warranted.

PMID- 22391956
TI  - An observational study to assess an electronic point-of-care wound documentation
      and reporting system regarding user satisfaction and potential for improved care.
AB  - The integration of information technology into daily patient care potentially
      provides a means to standardize care and enable continuous quality improvement
      through improved communication among care teams. A 2-month observational study
      was conducted on 38 residents with pressure ulcers at a 51-bed skilled nursing
      facility to rate the Ease of Use and Wound Management Effectiveness of a point-of
      care electronic wound documentation system. Nine nurses evaluated the use of
      handheld "smart phone" devices equipped with a digital camera to document
      pressure ulcer assessment and treatment at point of care. Ease of Use (five
      items) was scored on a 5-point Likert scale (5 = very easy); Wound Management
      Effectiveness (eight items) was scored on a 5-point Likert scale (5 = very
      effective). Statistically significant mean changes in nurses' ratings were found
      for baseline compared to 2-month follow-up by paired t-test. Ease of Use ratings
      across the five criteria increased from an overall mean of 3.3 at baseline to 4.7
      at follow-up (P = 0.5), while Wound Management Effectiveness increased from an
      overall mean of 3.3 at baseline to 4.4 at follow-up (P = 0.5) . The greatest
      gains for single items were reviewing wound progress (mean difference = 2.35; P =
      0.000) and recognizing changes in wound status (mean difference = 1.78; P =
      0.001) within the Ease of Use and Wound Management Effectiveness scales,
      respectively. The smallest change occurred in reading charts and notes (mean
      difference = 0.89) and ability to determine resident's risk level (mean
      difference = 0.39). Further research is needed to assess use of a wound
      documentation system in this and other settings, as well as to ascertain validity
      and reliability.

PMID- 22391958
TI  - Activation of transient receptor potential vanilloid subtype 1 increases
      expression and permeability of tight junction in normal and hyposecretory
      submandibular gland.
AB  - Tight junction (TJ) is an important structure that regulates material transport
      through the paracellular pathway across the epithelium, but its significance in
      salivary physiology and pathogenesis of salivary dysfunctional diseases is not
      fully understood. We previously demonstrated that a functional transient receptor
      potential vanilloid subtype 1 (TRPV1) expresses in submandibular gland (SMG).
      However, association of TRPV1-induced saliva secretion with TJ remains unknown.
      Here we explored the effect of TRPV1 activation on expression and function of TJ
      of rabbit SMG in vitro and in vivo. RT-PCR and western blot analysis revealed
      that capsaicin upregulated expression of zonula occludin-1 (ZO-1), claudin (Cldn)
      3, and -11, but not Cldn-1, -2, -4, -5, and -7 in cultured SMG cells. Capsaicin
      also increased the entering of 4 kDa FITC-dextran into the acinar lumen, induced
      redistribution of cytoskeleton F-actin under confocal microscope, and these
      effects were abolished by preincubation of capsazepine, a TRPV1 antagonist,
      indicating that activation of TRPV1 increases expression and permeability of TJ
      in SMG. Additionally, in a hyposecretory model induced by rabbit SMG
      transplantation, the expression of ZO-1, Cldn-3, and -11 was decreased, whereas
      other TJs remained unaltered. The structure of TJ was impaired and the width of
      apical TJs was reduced under transmission electron microscope, concomitant with
      diminished immunofluorescence of F-actin in peri-apicolateral region, indicating
      impaired TJ expression and decreased paracellular permeability in the
      transplanted SMG. Moreover, topical capsaicin cream increased secretion,
      decreased TJ structural injury, reversed TJ expression levels, and protected F
      actin morphology from disarrangement in transplanted SMGs. These data provide the
      first evidence to demonstrate that TJ components, particularly ZO-1, Cldn-3, and 
      11 have important roles in secretion of SMG under both physiological and
      pathophysiological conditions. The injury in TJ integrity was involved in the
      hypofunctional SMGs, and TRPV1 might be a potential target to improve saliva
      secretion through modulating expression and function of TJs.

PMID- 22391957
TI  - Wnt signaling induces epithelial-mesenchymal transition with proliferation in
      ARPE-19 cells upon loss of contact inhibition.
AB  - Proliferation and epithelial-mesenchymal transition (EMT) of the retinal pigment
      epithelium (RPE) are hallmarks of proliferative vitreoretinopathy. This study
      aims at clarifying the role of growth factors, such as epidermal growth factor
      (EGF), fibroblast growth factor-2 (FGF-2), and transforming growth factor-beta1
      (TGF-beta1), in controlling how RPE proliferates while undergoing EMT. When
      contact inhibition of post-confluent ARPE-19 cells was disrupted by EGTA, an
      increase of BrdU labeling was noted only in the presence of EGF and/or FGF-2, and
      was accompanied by EMT as evidenced by the loss of a normal RPE phenotype
      (altered cytolocalization of RPE65, N-cadherin, ZO-1, and Na,K-ATPase) and the
      gain of a mesenchymal phenotype (increased expression of vimentin, S100A4, and
      alpha-smooth muscle actin). EMT with proliferation by EGTA+EGF+FGF-2 was
      accompanied by activation of canonical Wnt signaling (judged by the TCF/LEF
      promoter activity, increased nuclear levels of and interaction between beta
      catenin and LEF1 proteins, and the replication by overexpression of beta
      catenin), abolished by concomitant addition of XAV939, a Wnt inhibitor, but not
      associated with suppression of Hippo signaling (negative expression of nuclear
      TAZ or YAP and cytoplasmic p-TAZ or p-YAP). The causative role of Wnt signaling
      on EMT with proliferation was confirmed by overexpression of stable S33Y beta
      catenin with EGTA treatment. In addition, contact inhibition disrupted by EGTA in
      the presence of TGF-beta1 also led to EMT, but suppressed proliferation and Wnt
      signaling. The Wnt signaling triggered by EGF+FGF-2 was sufficient and synergized
      with TGF-beta1 in activating the Smad/ZEB1/2 signaling responsible for EMT. These
      findings establish a framework for further dissecting how RPE might partake in a
      number of proliferative vitreoretinopathies characterized by EMT.

PMID- 22391959
TI  - Macrophages are related to goblet cell hyperplasia and induce MUC5B but not
      MUC5AC in human bronchus epithelial cells.
AB  - Airway goblet cell hyperplasia (GCH)--detectable by mucin staining--and abnormal
      macrophage infiltrate are pathological features present in many chronic
      respiratory disorders. However, it is unknown if both factors are associated.
      Using in-vivo and in-vitro models, we investigated whether macrophages are
      related with GCH and changes in mucin immunophenotypes. Lung sections from
      Sprague-Dawley rats treated for 48 h with one intra-tracheal dose of PBS or LPS
      (n=4-6 per group) were immunophenotyped for rat-goblet cells, immune, and
      proliferation markers. Human monocyte-derived macrophages (MDM) were pre-treated
      with or without LPS, immunophenotyped, and their supernatant, as well as
      cytokines at levels equivalent to supernatant were used to challenge primary
      culture of normal human bronchus epithelial cells (HBEC) in air-liquid interface,
      followed by MUC5B and MUC5AC mucin immunostaining. An association between
      increased bronchiolar goblet cells and terminal-bronchiolar proliferative
      epithelial cells confirmed the presence of GCH in our LPS rat model, which was
      related with augmented bronchiolar CD68 macrophage infiltration. The in-vitro
      experiments have shown that MUC5AC phenotype was inhibited when HBEC were
      challenged with supernatant from MDM pre-treated with or without LPS. In
      contrast, TNF-alpha and interleukin-1beta at levels equivalent to supernatant
      from LPS-treated MDM increased MUC5AC. MUC5B was induced by LPS, supernatant from
      LPS-treated MDM, a mix of cytokines including TNF-alpha and TNF-alpha alone at
      levels present in supernatant from LPS-treated MDM. We demonstrated that
      macrophages are related with bronchiolar GCH, and that they induced MUC5B and
      inhibited MUC5AC in HBEC, suggesting a role for them in the pathogenesis of
      airway MUC5B-related GCH.

PMID- 22391960
TI  - Incidence and clinical predictors of low defibrillation safety margin at time of
      implantable defibrillator implantation.
AB  - BACKGROUND: Determination of the defibrillation safety margin (DSM) is the most
      common method of testing device effectiveness at the time of implantation of
      implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy
      defibrillator (CRTD). Low DSM remains a problem in clinical practice. OBJECTIVE:
      The purpose of this study is to ascertain the incidence and clinical predictors
      of low DSM and the treatment strategies for low DSM in ICD or CRTD recipients.
      METHODS: Selected ICD or CRTD recipients from January 2006 to May 2008 who
      underwent DSM test at the time of implantation were included. Low DSM patients
      were defined as patients who had a DSM within 10 J of the maximum delivered
      energy of the device. These patients were compared to patients who had DSM > 10
      J. RESULTS: This study included 243 patients. Of these, 13 (5.3%) patients had
      low DSM, and 230 patients had adequate DSM. Patients with low DSM had a high
      prevalence of amiodarone use (69% vs 13%, p < 0.01), secondary prevention
      indications (69% vs 30%, p < 0.01), and a trend toward younger age (51 +/- 18 vs
      58 +/- 15 years, p = 0.08). After adjustment for age and sex, amiodarone use was
      significantly associated with low DSM. All low DSM patients except one obtained
      adequate DSM after taking additional steps, including discontinuing amiodarone
      and starting sotalol, RV lead repositioning, adding a subcutaneous array or shock
      coil, changing single-coil to dual-coil lead, and upgrading to a high output
      device. CONCLUSION: The incidence of low DSM patients is low with high-energy
      devices. Amiodarone use is associated with low DSM, and its discontinuation or
      substitution with sotalol is one of a variety of available options for low DSM
      patients.

PMID- 22391961
TI  - Assessment of atrial conduction time by tissue Doppler echocardiography and P
      wave dispersion in smokers.
AB  - INTRODUCTION: The aim of this study was to evaluate the relationship between
      cigarette smoking and atrial rhythm disorders with the use of noninvasive
      methods. METHODS: The study population consisted of 50 healthy volunteer smokers
      and 40 healthy volunteer non-smokers who had normal echocardiographic parameters
      and similar sex and age profiles. P-wave dispersion (PWD) was calculated from the
      12-lead surface ECG. Left ventricle (LV) end-systolic and end-diastolic
      diameters, LV ejection fraction, and interatrial and intraatrial
      electromechanical delay were measured by tissue Doppler imaging and conventional
      echocardiography. RESULTS: Isovolumetric relaxation time and deceleration time
      were significantly higher (91.5 +/- 11 vs. 82.35 +/- 8.6, p < 0.0001; 215.7 +/-
      37.1 vs. 175.3 +/- 17.7, p < 0.0001, respectively), and HDL cholesterol was
      significantly lower in smokers (39.34 +/- 7.5 vs.44.3 +/- 8.07, p = 0.003). There
      were no significant differences between the groups with respect to Sm and Em
      values, Am value, and E/A and E/Em ratios. However, the Em/Am ratio was
      significantly lower in smokers (1.28 +/- 0.21 vs. 1.44 +/- 0.33, p < 0.006).
      Inter- and intraatrial electromechanical delay were significantly higher in
      smokers when compared with non-smokers (51.11 +/- 1.54 vs. 27.30 +/- 3.36, p <
      0.0001, and 30.63 +/- 3.2 vs. 12.24 +/- 3.26, p < 0.0001, respectively). The
      amount of smoking was strongly correlated with interatrial electromechanical
      delay (r = 0.567, p < 0.0001), and a significant correlation was detected between
      PWD and interatrial electromechanical delay (r = 0.653, p = 0.001). CONCLUSION:
      We have demonstrated the relationship between inter- and intraatrial
      electromechanical delay and PWD. These parameters may be useful predictive
      markers for the development of AF in the asymptomatic period before cardiac
      rhythm disturbances occur. This finding may indicate that smokers have an
      increased risk of developing atrial rhythm disturbances.

PMID- 22391962
TI  - Laparoscopic excision of an antenatally diagnosed large simple hepatic cyst in
      the newborn.
AB  - Non-parasitic hepatic cysts are rare in infants and children. Advances in
      antenatal imaging have improved their detection, while development of
      laparoscopic techniques has expanded options for treatment. We present a case of
      an antenatally diagnosed non-parasitic hepatic cyst in a neonate, which was
      successfully excised laparoscopically with no recurrence.

PMID- 22391963
TI  - Dihydroarteminsin-induced apoptosis is not dependent on the translocation of Bim
      to the endoplasmic reticulum in human lung adenocarcinoma cells.
AB  - Bim, a proapoptotic BH3-only member of Bcl-2 family, has been considered to play
      an important role in initiating mitochondrial apoptotic pathway. Our previous
      studies have shown the ability of dihydroarteminsin (DHA) to induce apoptosis in
      human lung adenocarcinoma (ASTC-a-1) cells. In this study, we investigated the
      function of Bim during DHA-induced apoptosis in ASTC-a-1 and another human lung
      adenocarcinoma (A549) cell lines. Confocal imaging of single living cell
      expressing GFP-BimL showed the translocation of Bim to endoplasmic reticulum (ER)
      rather than mitochondria during DHA-induced apoptosis. Moreover, we also found
      that DHA induced ER stress and an increase of Bim protein levels. However,
      silencing Bim by short hairpin RNA did not inhibit DHA-induced caspase-9
      activation and cell apoptosis. Taken together, our results demonstrate for the
      first time that DHA induces Bim translocation to ER, but DHA-induced apoptosis is
      not dependent on Bim in ASTC-a-1 and A549 cell lines.

PMID- 22391964
TI  - Whey protein versus whey protein hydrolyzate for the protection of azoxymethane
      and dextran sodium sulfate induced colonic tumors in rats.
AB  - Recent studies have shown that whey protein has many useful effects including its
      anti-cancer effect. In this study we have compared the protective effect of
      dietary whey protein with whey protein hydrolyzate against azoxymethane and
      dextran sodium sulfate induced colon cancer in rats. We used a rat model of the
      colon cancer induced by administration of azoxymethane followed by repeated
      dextran sodium sulfate ingestion which causes multiple tumor development. Colon
      tissues were analyzed histologically in addition to biochemical analyses
      performed by measuring lipid peroxidation, protein oxidation and glutathione
      levels in both of colon and liver tissues of rats after sacrification.
      Macroscopic and microscopic tumors were identified in all groups that received
      azoxymethane followed by repeated dextran sodium sulfate. Group fed with whey
      protein hydrolyzate showed significantly less macroscopic and microscopic tumor
      development compared with group fed with whey protein. The protocol applied to
      generate an appropriate model of colon cancer was successful. Whey protein
      hydrolyzate was found to be more effective in preventing colon tumor development
      compared with whey protein.

PMID- 22391965
TI  - Controversial effect of two methylguanidine-based ionic liquids on firefly
      luciferase.
AB  - The importance and applicability of ionic liquids (ILs) in biocatalysis have been
      well recognized. ILs have growing interest as new and highly efficient reaction
      mediums for biocatalytic reactions, but as a reaction milieu for firefly
      luciferase has not been tested. In this report, the effects of two
      tetramethylguanidine-based ionic liquids on the activity and stability of
      Photinus pyralis luciferase were investigated. In spite of a common cationic
      part, luciferase activity increased up to 0.25 M of [TMG][Lac] but decreased in
      the presence of similar concentrations of [TMG][Pro]. Optimum temperature and
      thermal stability studies show more stability of luciferase only in the presence
      of [TMG][Lac]. The change in light intensity of firefly luciferase in the
      presence of both ILs was brought about without effect on bioluminescence emission
      spectra. The rate of light decay in the presence of both ILs was slower than
      native luciferase. 

PMID- 22391966
TI  - Glycosaminoglycan polysaccharide biosynthesis and production: today and tomorrow.
AB  - Glycosaminoglycans [GAGs] are essential heteropolysaccharides in vertebrate
      tissues that are also, in certain cases, employed as virulence factors by
      microbes. Hyaluronan [HA], heparin, and chondroitin sulfate [CS] are GAGs
      currently used in various medical applications and together are multi-billion
      dollar products thus targets for production by animal-free manufacture. By using
      bacteria as the source of GAGs, the pathogen's sword may be converted into a
      plowshare to help avoid potential liabilities springing from the use of animal
      derived GAGs including adventitious agents (e.g., prions, pathogens),
      antigenicity, degradation of the environment, and depletion of endangered
      species. HA from microbes, which have a chemical structure identical to human HA,
      has already been commercialized and sold at the ton-scale. Substantial progress
      towards microbial heparin and CS has been made, but these vertebrate polymers are
      more complicated structurally than the unsulfated bacterial polysaccharide
      precursors thus require additional processing steps. This review provides an
      overview of GAG structure, medical applications, microbial biosynthesis, and the
      state of bacterial GAG production systems. Representatives of all
      glycosyltransferase enzymes that polymerize the sugar chains of the three main
      GAGs have been identified and serve as the core technology to harness, but the
      proteins involved in sugar precursor formation and chain export steps of
      biosynthesis are also essential to the GAG production process. In addition, this
      review discusses future directions and potential important issues. Overall, this
      area is poised to make great headway to produce safer (both increased purity and
      more secure supply chains) non-animal GAG-based therapeutics.

PMID- 22391967
TI  - Expression and regulation of genes encoding lignocellulose-degrading activity in
      the genus Phanerochaete.
AB  - As white-rot basidiomycetes, Phanerochaete species are critical to the cycling of
      carbon sequestered as woody biomass, and are predicted to encode many enzymes
      that can be harnessed to promote the conversion of lignocellulose to sugars for
      fermentation to fuels and chemicals. Advances in genomic, transcriptomic, and
      proteomic technologies have enabled detailed analyses of different Phanerochaete
      species and have revealed numerous enzyme families required for lignocellulose
      utilization, as well as insight into the regulation of corresponding genes.
      Recent studies of Phanerochaete are also exemplified by molecular analyses
      following cultivation on different wood preparations, and show substrate
      dependent responses that were difficult to predict using model compounds or
      isolated plant polysaccharides. The aim of this mini-review is to synthesize
      results from studies that have applied recent advances in molecular tools to
      evaluate the expression and regulation of proteins that contribute to
      lignocellulose conversion in Phanerochaete species. The identification of
      proteins with as yet unknown function are also highlighted and noted as important
      targets for future investigation of white-rot decay.

PMID- 22391968
TI  - Peculiarities of brown-rot fungi and biochemical Fenton reaction with regard to
      their potential as a model for bioprocessing biomass.
AB  - This work reviews the brown-rot fungal biochemical mechanism involved in the
      biodegradation of lignified plant cell walls. This mechanism has been acquired as
      an apparent alternative to the energetically expensive apparatus of
      lignocellulose breakdown employed by white-rot fungi. The mechanism relies, at
      least in the incipient stage of decay, on the oxidative cleavage of glycosidic
      bonds in cellulose and hemicellulose and the oxidative modification and
      arrangement of lignin upon attack by highly destructive oxygen reactive species
      such as the hydroxyl radical generated non-enzymatically via Fenton chemistry
      [Formula: see text]. Modifications in the lignocellulose macrocomponents
      associated with this non-enzymatic attack are believed to aid in the selective,
      near-complete removal of polysaccharides by an incomplete cellulase suite and
      without causing substantial lignin removal. Utilization of this process could
      provide the key to making the production of biofuel and renewable chemicals from
      lignocellulose biomass more cost-effective and energy efficient. This review
      highlights the unique features of the brown-rot fungal non-enzymatic, mediated
      Fenton reaction mechanism, the modifications to the major plant cell wall
      macrocomponents, and the implications and opportunities for biomass processing
      for biofuels and chemicals.

PMID- 22391969
TI  - Pathway redesign for deoxyviolacein biosynthesis in Citrobacter freundii and
      characterization of this pigment.
AB  - Violacein (Vio) is an important purple pigment with many potential bioactivities.
      Deoxyviolacein, a structural analog of Vio, is always synthesized in low
      concentrations with Vio in wild-type bacteria. Due to deoxyviolacein's low
      production and difficulties in isolation and purification, little has been
      learned regarding its function and potential applications. This study was the
      first effort in developing a stable and efficient biosynthetic system for
      producing pure deoxyviolacein. A recombinant plasmid with vioabce genes was
      constructed by splicing using an overlapping extension-polymerase chain reaction,
      based on the Vio-synthesizing gene cluster of vioabcde, originating from
      Duganella sp. B2, and was introduced into Citrobacter freundii. With the viod
      gene disrupted in the Vio synthetic pathway, Vio production was completely
      abolished and the recombinant C. freundii synthesized only deoxyviolacein.
      Interestingly, vioe gene expression was strongly stimulated in the viod-deleted
      recombinant strain, indicating that viod disruptions could potentially induce
      polar effects upon the downstream vioe gene within this small operon.
      Deoxyviolacein production by this strain reached 1.9 g/L in shaker flasks. The
      product exhibited significant acid/alkali and UV resistance as well as
      significant inhibition of hepatocellular carcinoma cell proliferation at low
      concentrations of 0.1-1 MUM. These physical characteristics and antitumor
      activities of deoxyviolacein contribute to illuminating its potential
      applications.

PMID- 22391970
TI  - Amino acid substitutions in naphthalene dioxygenase from Pseudomonas sp. strain
      NCIB 9816-4 result in regio- and stereo-specific hydroxylation of flavanone and
      isoflavanone.
AB  - Wild-type naphthalene dioxygenase (NDO) from Pseudomonas sp. strain NCIB 9816-4
      transforms relatively planar flavone and isoflavone to cis-dihydrodiols. However,
      this enzyme cannot catalyze the transformation of flavanone and isoflavanone in
      which a phenyl group bonds to the stereogenic C2 or C3 of the C-ring. Protein
      modeling suggested that Phe224 in the substrate binding site of NDO may play a
      key role in substrate specificity toward flavanone and isoflavanone. Site
      directed mutants of NDO with substitution of Phe224 with Tyr biotransformed only
      the (S)-stereoisomers of flavanone and isoflavanone, producing an 8-OH group on
      the A-ring. In contrast, the Phe224Cys and Phe224Gln substitutions, which used
      (2S)-flavanone as a substrate, and Phe224Lys, which transformed (2S)-flavanone
      and (3S)-isoflavanone, each showed lower activity than the Phe224Tyr
      substitution. The remainder of the tested mutants had no activity with flavanone
      and isoflavanone. Protein docking studies of flavanone and isoflavanone to the
      modeled mutant enzyme structures revealed that an expanded substrate binding
      site, due to mutation at 224, as well as appropriate hydrophobic interaction with
      the residue at 224, are critical for successful binding of the substrates.
      Results of this study also suggested that in addition to the previously known
      Phe352, the Phe224 site of NDO appears to be important site for expanding the
      substrate range of NDO and bringing regiospecific and stereospecific
      hydroxylation reactions to C8 of the flavanone and isoflavanone A-rings.

PMID- 22391971
TI  - Simple Deletion: a vector- and marker-free method to generate and isolate site
      directed deletion mutants.
AB  - We have designed a new vector- and marker-free site-directed deletion system for
      gram-negative bacteria. In this system, a specific DNA fragment is amplified from
      a parental strain by using polymerase chain reaction (PCR), then circularized and
      introduced back into the parental strain for homologous recombination. The
      recombinant mutant is then detected and isolated by PCR-based sib selection.
      Unlike conventional methods, our Simple Deletion method requires no cloning
      procedures, and no foreign genes such as antibiotic-resistance genes are
      introduced as selection markers. The resulting mutant is, therefore, the same as
      the parental strain except for the lack of the target region. This method is
      categorized as a type of "self-cloning," and the resulting mutant can be used for
      laboratory research without restrictions. Using this method, we generated a
      mutant of a plant pathogenic bacterium, Xanthomonas campestris pv. campestris, in
      which the 20.4-kb hrp gene cluster involved in the type III secretion system and
      in pathogenicity was deleted. In addition, we proved that this method can also be
      used to delete smaller DNA regions of X. campestris pv. campestris and to
      generate deletion mutants of the bacterium Ralstonia solanacearum.

PMID- 22391972
TI  - Microbial heparin/heparan sulphate lyases: potential and applications.
AB  - Heparin/heparan sulphate glycosaminoglycans (HSGAGs) are composed of linear
      chains of 20-100 disaccharide units of N-acetylated D: -glucosamine alpha (1-4)
      linked to glucuronic acid. HSGAGs are widely distributed on the cell surface and
      extracellular cell matrix of virtually every mammalian cell type and play
      critical role in regulating numerous functions of blood vessel wall, blood
      coagulation, inflammation response and cell differentiation. These
      glycosaminoglycans present in this extracellular environment very significantly
      influence the blood coagulation system and cardiovascular functions. Recent
      studies have investigated the mechanism by which cancer causes thrombosis and
      emphasizes the importance of the coagulation system in angiogenesis and tumour
      metastasis. Heparan sulphate/heparin lyases or heparinases are a class of enzymes
      that are capable of specifically cleaving the (1-4) glycosidic linkages in
      heparin and heparan sulphate to generate biologically active oligosaccharides
      with substantially significant and distinct clinical, pharmaceutical and
      prophylactic/therapeutic applications. Bioavailability and pharmacokinetic
      behaviour and characteristics of these oligosaccharides vary significantly
      depending on the origin/nature of the substrate (heparin or heparan sulphate-like
      glycosaminoglycans), the source of enzyme and method of preparation. Various
      microorganisms are reported/patented to produce these enzymes with different
      properties. Heparinases are commercially used for the depolymerization of
      unfractionated heparin to produce low molecular weight heparins (LMWHs), an
      effective anticoagulant. Individual LMWHs are chemically different and unique and
      thus cannot be interchanged therapeutically. Heparinases and LMWHs are reported
      to control angiogenesis and metastasis also. This review catalogues the
      degradation of HSGAGs by microbial heparin/heparan sulphate lyases and their
      potential either specific to the enzymes or with the dual role for generation of
      oligosaccharides for a new generation of compounds, as shown by various
      laboratory or clinical studies.

PMID- 22391973
TI  - Quantitative colorimetric measurement of cellulose degradation under microbial
      culture conditions.
AB  - We have developed a simple, rapid, quantitative colorimetric assay to measure
      cellulose degradation based on the absorbance shift of Congo red dye bound to
      soluble cellulose. We term this assay "Congo Red Analysis of Cellulose
      Concentration," or "CRACC." CRACC can be performed directly in culture media,
      including rich and defined media containing monosaccharides or disaccharides
      (such as glucose and cellobiose). We show example experiments from our laboratory
      that demonstrate the utility of CRACC in probing enzyme kinetics, quantifying
      cellulase secretion, and assessing the physiology of cellulolytic organisms.
      CRACC complements existing methods to assay cellulose degradation, and we discuss
      its utility for a variety of applications.

PMID- 22391974
TI  - Reversible immobilization of glucoamylase onto magnetic chitosan nanocarriers.
AB  - A simple preparation process for the monodispersed pH-sensitive core-shell
      magnetic microspheres was carried out consisting of chitosan self-assembled on
      magnetic iron oxide nanoparticles. Meanwhile, glucoamylase was immobilized as a
      model enzyme on this carrier of Fe(3)O(4)/CS microspheres by ionic adsorption.
      The morphology, inner structure, and high magnetic sensitivity of the resulting
      magnetic chitosan microspheres were studied, respectively, with a field emission
      scanning electron microscope (SEM), transmission electron microscope (TEM), FT-IR
      spectroscopy, thermogravimetric analysis (TGA), and a vibrating sample
      magnetometer (VSM). Subsequently, the properties of glucoamylase immobilized on
      the regenerated supports were also investigated by determining storage stability,
      pH stability, reusability, magnetic response, and regeneration of supports. The
      results from characterization and determination remarkably indicated that the
      immobilized glucoamylase obtained presents excellent storage stability, pH
      stability, reusability, magnetic response, and regeneration of supports.
      Therefore, this kind of magnetic Fe(3)O(4)/CS microspheres with perfect
      monodispersity should be an ideal support for enzyme immobilization.

PMID- 22391975
TI  - Tumefactive postmenopausal gonadotroph cell hyperplasia.

PMID- 22391977
TI  - Outcome of transilluminated powered phlebectomy for varicose vein: review of 299
      patients (447 limbs).
AB  - PURPOSE: Varicose vein incompetence in the legs is very prevalent in the Korean
      population. New technologies and improvements in established methods have changed
      the treatment of varicose veins. Transilluminated powered phlebectomy is an
      alternative surgical technique that combines endoscopic powered vein resection
      and ablation of superficial varicosities with tumescent anesthesia and irrigated
      illumination. The present study sought to determine the clinical efficacy and
      safety of transilluminated powered phlebectomy from clinical data. METHOD: Four
      hundred and forty-seven limbs in 299 patients (157 male, 142 female; mean age
      50.6 years) with varicose veins were treated with transilluminated powered
      phlebectomy over a 7-year period. The patients were followed for 1 year
      postoperatively. The analyzed data included sex, age, body mass index, operative
      time (from skin incision to the application of elastic bandages on the legs for
      compression purposes), and postoperative complications. RESULTS: The mean
      operative time was 87.2 min for both limbs and 57.3 min for single limbs. The
      median number of incisions was five. Postoperative complications included an
      episode of cellulitis in 10 patients (2.2%), wound abscess in two patients
      (0.4%), hematoma in 15 patients (3.4%), residual veins in five patients (1.1%),
      cutaneous nerve damage in 10 patients (2.2%), and seroma in 13 patients (2.9%).
      No skin perforation and deep venous thrombosis were observed at the 1-year follow
      up. CONCLUSION: Transilluminated powered phlebectomy is an effective and safe
      method for the excision of varicosities.

PMID- 22391976
TI  - Signaling pathways in pheochromocytomas and paragangliomas: prospects for future
      therapies.
AB  - There is currently no completely effective therapy available for metastatic
      pheochromocytomas or paragangliomas. Increasing understanding of the germline and
      somatic mutations leading to pheochromocytoma and paraganglioma development has
      revealed crucial insights into the molecular pathology of these tumors. A
      detailed understanding of the molecular pathway alterations giving rise to
      pheochromocytomas and paragangliomas should allow for the exploration and
      development of new effective molecular-targeted therapy options for this rare but
      frequently fatal malignancy. Molecular analysis has shown that
      pheochromocytoma/paraganglioma-promoting gene mutations can be divided into two
      major groups-clusters 1 and 2-following two different routes to tumorigenesis.
      Cluster 1 mutations are associated with pseudohypoxia and aberrant VEGF signaling
      while cluster 2 mutations are associated with abnormal activation of kinase
      signaling pathways such as PI3 kinase/AKT, RAS/RAF/ERK, and mTORC1/p70S6K
      suggesting relevant targets for novel molecular-targeted therapy approaches which
      will be discussed in detail in this chapter.

PMID- 22391978
TI  - Intramural pseudocyst of the duodenum caused by pancreatic head cancer: report of
      a case.
AB  - An intramural pseudocyst in the alimentary tract develops as a rare complication
      of acute pancreatitis or trauma. A 60-year-old woman with pancreatic head cancer
      underwent preoperative radiological examinations, which revealed a 45-mm cystic
      mass around the second portion of the duodenum. Endoscopic ultrasonography
      confirmed a cystic lesion in the submucosal layer of the duodenum and fine needle
      aspiration cytology of the cystic contents suggested adenocarcinoma. The cystic
      fluid was amylase-rich, at 17040 U/l. We performed pancreaticoduodenectomy for
      the pancreatic head cancer. Pancreatography of the resected specimen showed a
      communication between the main pancreatic duct and the cystic lesion. The cut
      surface of the resected specimen revealed a cystic lesion, which surrounded the
      duodenum. Pathologically, the cystic lesion was diagnosed as a pseudocyst,
      located between the dissociated smooth muscle layers of the duodenum.

PMID- 22391979
TI  - Hepatic resection using a liver-hanging maneuver and Glissonean pedicle
      transection for hepatocellular carcinoma in a patient with situs inversus
      totalis: report of a case.
AB  - Situs inversus totalis is a rare congenital anomaly in which the major abdominal
      organs are located as a mirror image of their normal positions. This poses much
      difficulty for surgeons. We describe how we performed the liver-hanging maneuver
      (LHM) for hepatocellular carcinoma (HCC) in a 59-year-old man with situs inversus
      totalis, to resolve the difficulty of the mirror-image location of his liver. The
      HCC was located in the right lateral sector. Although segmentectomy of segment 7
      would normally be considered minimal for a curative treatment of HCC, this was
      relatively complicated in this patient. Thus, we performed an extended right
      lateral sectionectomy using the LHM to achieve a simple transection. The hepatic
      hilum was dissected using the Glissonean pedicle transection method. The
      operation time and intraoperative blood loss were 6 h 45 min and 471 ml,
      respectively. No blood product transfusion was required. The LHM and the hilar
      Glissonean pedicle approach proved effective for resolving the difficulties of
      performing surgery in a mirror image for HCC in a patient with situs inversus
      totalis.

PMID- 22391980
TI  - Questionnaire survey regarding the current status and controversial issues
      concerning reconstruction after gastrectomy in Japan.
AB  - The Japanese Society for the Study of Postoperative Morbidity after Gastrectomy
      conducted a nationwide questionnaire survey to clarify the current status of
      reconstruction after gastrectomy. One hundred and forty-five institutions (66%)
      responded to the survey. The questionnaire dealt with the reconstruction after a
      distal gastrectomy, pylorus-preserving gastrectomy (PPG), total gastrectomy, and
      proximal gastrectomy. The most common method of reconstruction after distal
      gastrectomy was Billroth I in 112 institutions (74%), and Roux-en-Y (RY) in 30
      (21%). Seventy-seven institutions (53%) responded to the PPG questions. The
      lengths of the antral cuff were widely distributed among the institutions.
      Segmental gastrectomy was performed by 23 institutions for limited cases. The
      most common method of reconstruction after total gastrectomy was RY in 138
      institutions (95%). Reconstruction with a pouch after total gastrectomy was done
      in 26 institutions (18%). The most common reconstructions after proximal
      gastrectomy were esophagogastrostomy in 69 institutions (48%), jejunal
      interposition in 41 (28%), double tract in 19 (13%) and pouch reconstruction in 6
      (7%). Although most Japanese surgeons are concerned about the revised methods of
      reconstruction and quality of life after gastrectomy, surgeons have not yet
      reached a full consensus on these issues.

PMID- 22391981
TI  - Carcinosarcoma of the gallbladder: report of two cases.
AB  - Adenocarcinoma is the predominant histological type of carcinoma of the
      gallbladder, accounting for more than 80% of all gallbladder carcinomas. In
      contrast, carcinosarcoma of the gallbladder is an extremely atypical subset of
      gallbladder malignancies. It is characterized by the presence of both epithelial
      and mesenchymal components. Currently, fewer than 100 cases have been reported in
      the English literature. Therefore, knowledge and experience regarding this
      disease are limited. Recently, we experienced two cases of gallbladder
      carcinosarcoma, which were diagnosed as gallbladder carcinoma based on the
      preoperative clinical and radiological examinations. Cholecystectomies were
      performed in both cases, and the malignant tumor cells included carcinomatous and
      sarcomatous components histologically. The final pathological diagnoses were
      carcinosarcoma of the gallbladder. We herein report these two cases of
      gallbladder carcinosarcoma and review the previous pertinent literature.

PMID- 22391982
TI  - Intersectoral planning for city health development.
AB  - The article reviews the evolution and process of city health development planning
      (CHDP) in municipalities participating in the European Network of Healthy Cities
      organized by the European Region of the World Health Organization. The concept of
      CHDP combines elements from three theoretical domains: (a) health development,
      (b) city governance, and (c) urban planning. The setting was the 77 cities which
      participated in Phase IV (2003-2008) of the network. Evidence was gathered
      principally from a general evaluation questionnaire sent to all network cities.
      CHDPs are strategic documents giving direction to municipalities and partner
      agencies. Analysis revealed a trend away from "classic" CHDPs with a primary
      focus on health development towards ensuring a health dimension to other sector
      plans, and into the overarching strategies of city governments. Linked to the
      Phase IV priority themes of Healthy aging and healthy urban planning, cities
      further developed the concept and application of human-centered sustainability.
      More work is required to utilize cost-benefit analysis and health impact
      assessment to unmask the synergies between health and economic prosperity.

PMID- 22391983
TI  - The emerging of xylazine as a new drug of abuse and its health consequences among
      drug users in Puerto Rico.
AB  - During the last decade, the veterinary anesthetics have gained popularity as
      recreational drugs. The aim of this study was to document the use of "anestecia
      de caballo" (xylazine) and its consequences among drug users in Puerto Rico. The
      study combined a cross-sectional survey with 89 drug users and two focus groups
      conducted in Mayaguez with frontline drug treatment providers. Drug users were
      recruited from communities of the San Juan metropolitan area using a variety of
      ethnographic and outreach strategies. A short questionnaire developed for the
      study collected information on sociodemographics, xylazine use, and its
      consequences. The two focus groups were conducted to discuss the details related
      to xylazine use, its consequences, and utilization awareness. The sample
      comprised 63 males (70.8%) and 26 females with a mean age of 37.2 years. The mean
      number of years of drug use was 14.3, with a mean frequency of drug use of 5.9
      times daily. More than 65% reported speedball as the principal drug of use. The
      prevalence of xylazine use was 80.7%. More than 42% of the sample used xylazine
      in a mixture with speedball. The main route of administration of xylazine was
      injection but 14% reported the use of xylazine by inhalation. More than 35% of
      the sample reported skin lesions and 21.1% reported at least one overdose
      episode. Multiple logistic regression analysis revealed that males (OR = 3.47, CI
      = 1.10-12.00) and those who reported speedball as their main drug of use (OR =
      9.34, CI = 2.51-34.70) were significantly more likely to be xylazine users. Focus
      groups revealed that drug users claimed to recognize the presence of xylaxine in
      a mixture of speedball based on its effects, taste, the color of the drug (dark
      brown), and its odor. In conclusion, the use of xylazine among drug users in
      Puerto Rico seems to be an emerging trend with potentially serious health
      consequences.

PMID- 22391984
TI  - Prevalence and characteristics of femoral injection among Seattle-area injection
      drug users.
AB  - Injection drug use (IDU) into central veins, most common among long-term IDUs
      with no other options, can lead to severe infectious, vascular, and traumatic
      medical consequences. To follow-up on anecdotal reports of femoral vein injection
      and related medical problems in Seattle, we analyzed data from the annual survey
      of a community-based syringe exchange program. A total of 276 (81%) of 343
      program attendees completed the survey in August 2010. Among 248 IDUs, 66% were
      male, 78% white, and 86% primarily injected opiates. One hundred respondents
      (40%) had injected into the femoral vein, 55% of whom were actively doing so, and
      58% of whom reported medical complications that they attributed to the practice.
      Most (66%) used the femoral vein due to difficulty accessing other veins,
      although 61% reported other veins they could access and 67% reporting using other
      sites since initiating femoral injection. While injecting into muscle was more
      frequent among older IDUs with longer injection careers, the prevalence of
      femoral injection was highest among respondents in their late twenties with 2.5-6
      years of injecting drugs. Multivariate analysis demonstrated an increased risk of
      initiating femoral injection each calendar year after 2007. Injecting into the
      femoral vein was also associated with white versus other race (odds ratio [OR]
      2.7, 95% CI 1.3-5.4) and injection of primarily opiates versus other drugs (OR
      6.3, 95% CI 1.2-32.9) and not associated with age, length of IDU career, or a
      history of injecting into muscle. These findings suggest a secular trend of
      increasing femoral injection among Seattle-area IDUs with a high rate of related
      medical problems. Interventions, such as education regarding the hazards of
      central venous injection and guidance on safe injection into peripheral veins,
      are needed to minimize the health consequences of femoral injection.

PMID- 22391985
TI  - Fetal liver calcifications: an autopsy study.
AB  - Fetal liver calcifications are occasionally found in fetal autopsies. However,
      the incidence, associated findings, clinical significance, and presumed
      pathogenesis of fetal liver calcifications are not well documented. This study
      analyzed the characteristics and significance of fetal liver calcifications found
      on fetal autopsies. Cases of fetal liver calcifications were collected from a
      fetal autopsy database. Their clinical and pathological characteristics were
      analyzed in comparison to the remaining cases in the database. Thirty-five cases
      (4.2%) of fetal liver calcifications were found among 827 consecutive fetal
      autopsies that had been performed in our hospital during the 16-year period from
      January 1, 1994 through December 31, 2009. Twenty-nine cases had nodular
      calcifications, predominantly subcapsular. Calcification in portal spaces and
      porta hepatis were present in six cases. Twenty cases were missed abortions and
      intrauterine fetal death. Missed abortion at or earlier than 23 weeks had
      significantly more subcutaneous edema and other evidence of circulatory
      abnormalities. Calcifications in older fetuses (>23 weeks) were located more
      commonly in portal spaces and in other organs. Fetal liver calcification is an
      incidental finding during autopsies. The significance of fetal liver
      calcifications has to be assessed in combination with other clinical and
      pathological parameters, including location and number of the lesions, signs of
      circulatory compromise, and abnormalities of placenta, umbilical cord, and fetal
      malformations. Fetal liver calcifications are commonly associated with conditions
      related to impaired circulation, including umbilical cord abnormalities and
      subcutaneous edema. We suggest that fetal liver calcifications might attest to
      circulatory compromise preceding death, especially if subcutaneous edema is
      present and even when no other abnormal findings are seen.

PMID- 22391986
TI  - Evaluation of atrial conduction features with tissue Doppler imaging in patients
      with chronic obstructive pulmonary disease.
AB  - BACKGROUND: The electrical activity of atria can be demonstrated by P waves on
      surface electrocardiogram (ECG). Atrial electromechanical delay (AEMD) measured
      with tissue Doppler imaging (TDI) echocardiography can be a useful non-invasive
      method for evaluating atrial conduction features. We investigated whether AEMD is
      prolonged in patients with chronic obstructive pulmonary disease (COPD). PATIENTS
      AND METHODS: Study consisted of 41 (15 female, 26 male, mean age 62 + 12 years)
      patients with COPD and 41 healthy subjects. Pulmonary function tests,12 lead
      surface ECG and echocardiographic examination were performed and recorded. P wave
      changes on surface ECG, minimum (P (min)) and maximum (P (max)) duration of P
      wave and its difference as P wave dispersion (P (wd)) were measured and recorded.
      Atrial electromechanic delay (AEMD) was calculated from colored-TDI recordings.
      RESULTS: Pulmonary functions were significantly lower in COPD group than the
      control group as expected. Right atrial areas and pulmonary arterial systolic
      pressures (PAP) were significantly higher in COPD group than the controls (right
      atrial area: 11.9 +/- 3.4 cm(2) and 8.2 +/- 2.2 cm(2), p < 0.0001 and PAP: 38.4
      +/- 12.2 and 19.0 +/- 3.2 mmHg p < 0.0001, respectively). P wave intervals on
      surface ECG were significantly increased in COPD patients than the control group
      (P (max): 105 +/- 11 and 90 +/- 12 ms, p < 0.0001; P (min): 60 +/- 12 and 51 +/-
      10 ms, p = 0.003 and P (wd): 39 +/- 10 and 31 +/- 7 ms, p < 0.0001). According to
      the AEMD measurements from different sites by TDI, there was a significant delay
      between the onset of the P wave on surface ECG and the onset of the late
      diastolic wave in patients with COPD when compared with controls measured from
      tricuspid lateral septal annulus (TAEMD) (COPD: 41.3 +/- 9.8 ms, control: 36 +/-
      4.5 ms; p = 0.005). There was a positive correlation between TAEMD and right
      atrial area (r = 0.63, p < 0.0001) and also between TAEMD and PASP (r = 0.43, p <
      0.0005) and a negative correlation between TAEMD and forced expiratory volume
      (FEV1) (r = -0.44, p = 0.04). CONCLUSIONS: Right atrial electromechanical delay
      is significantly prolonged in patients with COPD. The right atrial area, PAP and
      FEV1 levels are important factors of this prolonged delay. Also the duration of
      atrial depolarization is significantly prolonged and propagation of
      depolarization is inhomogeneous in patients with COPD. These may be the
      underlying mechanisms to explain the atrial premature beats, multifocal atrial
      tachycardia, atrial flutter and fibrillation often seen in patients with COPD
      secondary to these changes.

PMID- 22391987
TI  - Comparison of HbA1c and oral glucose tolerance test for diagnosis of diabetes in
      patients with coronary artery disease.
AB  - BACKGROUND: Measurement of glycated hemoglobin A1c (HbA1c) to diagnose diabetes
      mellitus (DM-2) is recommended by several expert groups. DM-2 occurs very
      frequently among patients with coronary artery disease (CAD). Therefore, we aimed
      to investigate the diagnostic strengths of HbA1c and oral glucose tolerance test
      (OGTT) in detecting latent glucometabolic disturbances among patients with CAD.
      MATERIALS AND METHODS: One hundred ninety-nine consecutive patients admitted with
      CAD were included in this observational study. Fasting plasma glucose as well as
      HbA1c measurement was performed in all study participants and those without
      preexisting DM-2 underwent an OGTT. RESULTS: Patients were subdivided according
      to their medical history into those with previous DM-2 (n = 37). The remaining
      162 patients underwent OGTT, which revealed 39 patients with diabetes (DM
      (OGTT)), 35 with impaired glucose tolerance (IGT), 20 with impaired fasting
      glucose (IFG) and 68 with normal glucose tolerance (NGT). Using HbA1c resulted in
      6.8% DM and 45.6% at risk (HbA1c 5.7-6.4%) diagnosis. OGTT identified 24.1% DM (p
      = 0.002 compared with HbA1c) and 21.6% IGT patients. Among those with
      intermediate HbA1c (5.7-6.4%) 26.5% patients were NGT and only 30.9% displayed DM
      2 by use of OGTT. Among patients with HbA1c of <5.7%, 44% (n = 31) of patients
      had disturbed glucose metabolism. Using receiver-operating curve HbA1c cutoff
      with the highest sensitivity and specificity was found to be 5.8%. DISCUSSION:
      There is a large discordance between OGTT and HbA1c in terms of detecting latent
      DM-2 in patients with CAD. Measurement of HbA1c could result in lower propensity
      of DM-2 diagnosis.

PMID- 22391988
TI  - Lasting reduction of heart transplant tachycardia with ivabradine is effective
      and well tolerated: results of 48-month study.
AB  - The safety and efficacy of ivabradine applied in heart transplant (HTx)
      recipients with permanent sinus tachycardia (PST) has been depicted in previous
      short-term follow-up studies. We sought to investigate the long-term impact of
      ivabradine in this patient population. From May to November 2006, 29 HTx
      recipients with PST, who exhibited either contraindications or intolerance of
      beta-blocker medication or insufficient heart rate (HR) reduction on beta-blocker
      treatment, first received oral ivabradine treatment (5 mg bid). Ivabradine
      treatment was discontinued in three patients due to adverse events within the
      first week. In the remaining 26 patients, resting HR was significantly lowered
      from 106.8 +/- 9.2 at baseline to 83.2 +/- 5.1 bpm after 3 months (p < 0.001).
      This effect remained stable in the long-term follow-up (82.1 +/- 11.8 bpm after 4
      years), whilst blood pressure was not affected. Apart from the corrected QT
      interval (QTc), there were no significant changes in ECG. The elongated QTc at
      baseline (469.4 +/- 29.5 ms) decreased to 444.3 +/- 33.1 ms after 3 months
      ivabradine treatment (p < 0.001). A decrease in QTc until month 9 was observed,
      followed by a partial increase to the upper limit of the normal value. Neither
      allograft rejection nor changes in left ventricular ejection fraction were
      observed over the follow-up period. In conclusion, ivabradine appears to be a
      safe and feasible long-term therapeutic option for HTx recipients with PST. It
      reduced the resting HR without impairment of blood pressure, myocardial
      contractility and cardiac conduction. The prognostic value of normalised QTc
      following ivabradine administration requires further observation.

PMID- 22391989
TI  - Efficient on-chip isolation of HIV subtypes.
AB  - HIV has caused a global pandemic over the last three decades. There is an unmet
      need to develop point-of-care (POC) viral load diagnostics to initiate and
      monitor antiretroviral treatment in resource-constrained settings. Particularly,
      geographical distribution of HIV subtypes poses significant challenges for POC
      immunoassays. Here, we demonstrated a microfluidic device that can effectively
      capture various subtypes of HIV particles through anti-gp120 antibodies, which
      were immobilized on the microchannel surface. We first optimized an antibody
      immobilization process using fluorescent antibodies, quantum dot staining and AFM
      studies. The results showed that anti-gp120 antibodies were immobilized on the
      microchannel surface with an elevated antibody density and uniform antibody
      orientation using a Protein G-based surface chemistry. Further, RT-qPCR analysis
      showed that HIV particles of subtypes A, B and C were captured repeatably with
      high efficiencies of 77.2 +/- 13.2%, 82.1 +/- 18.8, and 80.9 +/- 14.0% from
      culture supernatant, and 73.2 +/- 13.6, 74.4 +/- 14.6 and 78.3 +/- 13.3% from
      spiked whole blood at a viral load of 1000 copies per mL, respectively. HIV
      particles of subtypes A, B and C were captured with high efficiencies of 81.8 +/-
      9.4%, 72.5 +/- 18.7, and 87.8 +/- 3.2% from culture supernatant, and 74.6 +/-
      12.9, 75.5 +/- 6.7 and 69.7 +/- 9.5% from spiked whole blood at a viral load of
      10,000 copies per mL, respectively. The presented immuno-sensing device enables
      the development of POC on-chip technologies to monitor viral load and guide
      antiretroviral treatment (ART) in resource-constrained settings.

PMID- 22391990
TI  - Characterization of exogenous bacterial oligosaccharyltransferases in Escherichia
      coli reveals the potential for O-linked protein glycosylation in Vibrio cholerae
      and Burkholderia thailandensis.
AB  - Bacterial protein glycosylation systems from varying species have been
      functionally reconstituted in Escherichia coli. Both N- and O-linked
      glycosylation pathways, in which the glycans are first assembled onto lipid
      carriers and subsequently transferred to acceptor proteins by an
      oligosaccharyltransferase (OTase), have been documented in bacteria. The
      identification and characterization of novel OTases with different properties may
      provide new tools for engineering glycoproteins of biotechnological interest. In
      the case of OTases involved in O-glycosylation (O-OTases), there is very low
      sequence homology between those from different bacterial species. The Wzy_C
      signature domain common to these enzymes is also present in WaaL ligases; enzymes
      involved in lipopolysaccharide biosynthesis. Therefore, the identification of O
      OTases using solely bioinformatic methods is problematic. The hypothetical
      proteins BTH_I0650 from Burkholderia thailandensis E264 and VC0393 from Vibrio
      cholerae N16961 contain the Wzy_C domain. In this work, we demonstrate that both
      proteins have O-OTase activity and renamed them PglL(Bt) and PglL(Vc),
      respectively, similar to the Neisseria meningitidis counterpart (PglL(Nm)). In E.
      coli, PglL(Bt) and PglL(Vc) display relaxed glycan and protein specificity.
      However, effective glycosylation depends upon a specific combination of the
      protein acceptor, glycan and O-OTase analyzed. This knowledge has important
      implications in the design of glycoconjugates and provides novel tools for use in
      glycoengineering applications. The codification of enzymatically active O-OTase
      in the genomes of members of the Vibrio and Burkholderia genera suggests the
      presence of still unknown O-glycoproteins in these organisms, which might have a
      role in bacterial physiology or pathogenesis.

PMID- 22391991
TI  - Simple isolation method for the bulk isolation of wear particles from metal on
      metal bearing surfaces generated in a hip simulator test.
AB  - Isolation and characterization of metal-on-metal (MoM) wear particles from
      simulator lubricants is essential to understand wear behaviour, ion release and
      associated corrosive activity related to the wear particles. Substantial
      challenges remain to establish a simple, precise and repeatable protocol for the
      isolation and analysis of wear particles due to their extremely small size, their
      tendency to agglomerate and degrade. In this paper, we describe a simple and
      efficient method for the bulk isolation and characterisation of wear particles
      from MoM bearings. Freeze drying was used to remove the large volume of water
      from the serum lubricant, enzymes used to digest the proteins and
      ultracentrifugation to finally isolate and purify the particles. The present
      study involved a total of eight steps for the isolation process and a wear
      particle extraction efficiency of 45% was achieved.

PMID- 22391993
TI  - Surface modification of titanium by hydrothermal treatment in Mg-containing
      solution and early osteoblast responses.
AB  - Surface modification on titanium was carried out in order to improve its
      bioactivity. Pure titanium was hydrothermally treated in distilled water and 0.1
      M MgCl(2) solutions at 200 degrees C for 24 h. Surface morphology, roughness,
      wettability and chemical composition were characterized before and after
      treatment. Bovine serum albumin was used as model to study protein adsorption.
      MC3T3-E1 cells were cultured and initial cell attachment, morphology,
      proliferation were evaluated. After hydrothermal treatment, nano-sized
      precipitations were observed and samples showed superhydrophilicity. Magnesium
      (Mg) was immobilized into titanium surface by hydrothermal treatment. Protein
      adsorption was significantly increased on Mg-containing samples. Cell attachment
      was improved and cell spreading was enhanced on Mg-containing samples compared
      with untreated or those treated in distilled water. Increased early cellular
      attachment on the MgTi surface resulted in subsequent increase of number of
      proliferated cells. Hydrothermal treatment in MgCl(2) solution was expected to be
      an effective method to fabricate titanium implant with good bioactivity.

PMID- 22391994
TI  - Preparation of injectable auto-forming alginate gel containing simvastatin with
      amorphous calcium phosphate as a controlled release medium and their therapeutic
      effect in osteoporosis model rat.
AB  - Highly soluble amorphous calcium phosphate powder (ACP) was added to the alginate
      gel as a buffering agent, in an attempt to enable widely controlled release while
      avoiding an acidification of the gel-environment. Therapeutic effects of the ACP
      containing alginate gel which slowly releases a drug, simvastatin, on
      osteoporosis model rats were examined. A model drug, simvastatin, incorporated in
      the alginate gel with ACP up to 0.5%, was continuously released for a long time
      under the acidic condition. The release rate was controlled by the amount of ACP,
      serving as a buffer to suppress acidity. When the alginate solution
      intramuscularly injected in the rat, a soft gel was formed in the injected site.
      Simvastatin released from the gel containing 0.5% of ACP showed high therapeutic
      effect on osteoporosis rat. Thus, the present injectable long-sustained release
      system is expected to be a novel drug delivery controlling device.

PMID- 22391995
TI  - Photocatalytic activity of low temperature oxidized Ti-6Al-4V.
AB  - Numerous advanced surface modification techniques exist to improve bone
      integration and antibacterial properties of titanium based implants and
      prostheses. A simple and straightforward method of obtaining uniform and
      controlled TiO(2) coatings of devices with complex shapes is H(2)O(2)-oxidation
      and hot water aging. Based on the photoactivated bactericidal properties of
      TiO(2), this study was aimed at optimizing the treatment to achieve high
      photocatalytic activity. Ti-6Al-4V samples were H(2)O(2)-oxidized and hot water
      aged for up to 24 and 72 h, respectively. Degradation measurements of rhodamine B
      during UV-A illumination of samples showed a near linear relationship between
      photocatalytic activity and total treatment time, and a nanoporous coating was
      observed by scanning electron microscopy. Grazing incidence X-ray diffraction
      showed a gradual decrease in crystallinity of the surface layer, suggesting that
      the increase in surface area rather than anatase formation was responsible for
      the increase in photocatalytic activity.

PMID- 22391996
TI  - No evidence for mevalonate shunting in moderately affected children with Smith
      Lemli-Opitz syndrome.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is caused by a genetic deficiency in 7
      dehydrocholesterol (7-DHC) reductase (EC 1.3.1.21), the last enzyme of the
      cholesterol synthetic pathway. In SLOS, plasma cholesterol concentration is
      reduced and immediate precursor concentration (7-DHC) is elevated. Surprisingly,
      total sterol synthesis is reduced but HMG-CoA reductase activity, a rate-limiting
      enzyme in cholesterol synthesis is unaltered as judged by normal urinary
      excretion of mevalonic acid (MVA) (Pappu et al. J Lipid Res 43:1661-1669, 2002).
      These findings raise the possibility of increased diversion of MVA into the MVA
      shunt pathway away from sterol synthesis, by activation of the shunt pathway
      enzymes. To test this hypothesis, we measured the urinary excretion of 3
      methylglutaconic acid (U-3MGC), a by-product of the shunt pathway, in 19 mildly
      to moderately severely affected SLOS subjects (ten males, nine females) receiving
      either a cholesterol-free or a high cholesterol diet, and in 20 age- and sex
      matched controls. U-3MGC was similar in SLOS and controls, and was unaffected by
      dietary cholesterol intake. Further, no change in U-3MGC was observed in a subset
      of SLOS subjects (n = 9) receiving simvastatin. In contrast, U-MVA was reduced by
      cholesterol supplementation (~54%, p < 0.05) and by simvastatin (~50%, p < 0.04).
      There was no correlation between U-3MGC and either plasma sterol concentrations,
      urinary isoprenoids, or the subjects' clinical severity score. However U-3MGC was
      inversely correlated with age (p < 0.04) and body weight (p < 0.02), and higher
      in females than in males (~65%, p < 0.025). The data show that DHCR7 deficiency
      does not result in 3MGC accumulation in SLOS and suggest that the MVA shunt
      pathway is not activated in patients with the condition.

PMID- 22391997
TI  - Tetrahydrobiopterin (BH4) in PKU: effect on dietary treatment, metabolic control,
      and quality of life.
AB  - BACKGROUND: Tetrahydrobiopterin (BH(4))-sensitive phenylketonuria (PKU) can be
      treated with sapropterin dihydrochloride. We studied metabolic control and health
      related quality of life (HRQoL) in PKU patients treated with BH(4). SUBJECTS AND
      METHODS: Based on the review of neonatal BH(4) test results and mutation analysis
      in 41 PKU patients, 19 were identified as potentially BH(4)-sensitive (9 females,
      10 males, age 4-18 years). We analyzed phenylalanine (phe) concentrations in
      dried blood samples, nutrition protocols, and HRQoL questionnaires (KINDL((r)))
      beginning from 1 year before, during the first 42 days, and after 3 months of
      BH(4) therapy. RESULTS: Eight BH(4)-sensitive patients increased their phe
      tolerance (629 +/- 476 vs. 2131 +/- 1084 mg, p = 0.006) while maintaining good
      metabolic control (phe concentration in dried blood 283 +/- 145 vs. 304 +/- 136
      MUM, p = 1.0). Six of them were able to stop dietary protein restriction
      entirely. BH(4)-sensitive patients had average HRQoL scores that were comparable
      to age-matched healthy children. There was no improvement in HRQoL scores after
      replacing classic dietary treatment with BH(4) supply, although personal reports
      given by the patients and their parents suggest that available questionnaires are
      inappropriate to detect aspects relevant to inborn metabolic disorders.
      DISCUSSION: BH(4) can allow PKU patients to increase their phe consumption
      significantly or even stop dietary protein restrictions. Unexpectedly, this does
      not improve HRQoL as assessed with KINDL((r)), partly due to high scores even
      before BH(4) therapy. Specific questionnaires should be developed for inborn
      metabolic disorders.

PMID- 22391999
TI  - The QWERTY effect: how typing shapes the meanings of words.
AB  - The QWERTY keyboard mediates communication for millions of language users. Here,
      we investigated whether differences in the way words are typed correspond to
      differences in their meanings. Some words are spelled with more letters on the
      right side of the keyboard and others with more letters on the left. In three
      experiments, we tested whether asymmetries in the way people interact with keys
      on the right and left of the keyboard influence their evaluations of the
      emotional valence of the words. We found the predicted relationship between
      emotional valence and QWERTY key position across three languages (English,
      Spanish, and Dutch). Words with more right-side letters were rated as more
      positive in valence, on average, than words with more left-side letters: the
      QWERTY effect. This effect was strongest in new words coined after QWERTY was
      invented and was also found in pseudowords. Although these data are
      correlational, the discovery of a similar pattern across languages, which was
      strongest in neologisms, suggests that the QWERTY keyboard is shaping the
      meanings of words as people filter language through their fingers. Widespread
      typing introduces a new mechanism by which semantic changes in language can
      arise.

PMID- 22391998
TI  - Progress in understanding 2-hydroxyglutaric acidurias.
AB  - The organic acidurias D: -2-hydroxyglutaric aciduria (D-2-HGA), L-2
      hydroxyglutaric aciduria (L-2-HGA), and combined D,L-2-hydroxyglutaric aciduria
      (D,L-2-HGA) cause neurological impairment at young age. Accumulation of D-2
      hydroxyglutarate (D-2-HG) and/or L-2-hydroxyglutarate (L-2-HG) in body fluids are
      the biochemical hallmarks of these disorders. The current review describes the
      knowledge gathered on 2-hydroxyglutaric acidurias (2-HGA), since the description
      of the first patients in 1980. We report on the clinical, genetic, enzymatic and
      metabolic characterization of D-2-HGA type I, D-2-HGA type II, L-2-HGA and D,L-2
      HGA, whereas for D-2-HGA type I and type II novel clinical information is
      presented which was derived from questionnaires.

PMID- 22392001
TI  - Economic methods in the century trial--a comprehensive lifestyle modification
      study for managing coronary artery disease.
AB  - While most studies assess the cost-effectiveness of treating acute coronary
      conditions, the Century Health Study for Cardiovascular Medicine (Century Trial)
      focuses on ameliorating coronary artery disease (CAD) through a comprehensive
      lifestyle modification program. This 1,300-patient phase III randomized study
      uses positron emission tomography for risk stratification, complemented with
      comprehensive educational and motivational therapy for patients with preclinical
      or established CAD. The Century Trial is in its second year of a five-year follow
      up protocol, and it is one of the first to combine imaging technology and
      lifestyle modification as a way to improve patient behavior and health. In this
      article, we present the economic study design used in the Century Trial and
      provide considerable methodological detail to serve as reference for other
      researchers. We describe the cost and effect estimation methods as well as our
      analysis and uncertainty modeling plans. The study will incorporate quality
      adjusted life years and use a societal perspective to measure both in-trial and
      lifetime costs through incremental cost-effectiveness ratios. The approach we
      follow should provide further evidence on the cost-effectiveness of comprehensive
      lifestyle modification programs in regressing coronary artery disease.

PMID- 22392002
TI  - [Complement--a phylogenetically old system as a new player in the development of
      atherosclerosis].
AB  - Atherosclerotic diseases such as coronary artery disease and ischaemic stroke are
      caused by chronic inflammation in arterial vessel walls. The complement system is
      part of the innate immune system. It is involved in many processes contributing
      to onset and development of atherosclerotic plaques up to the final stage of
      acute thrombotic events. This is due to its prominent role in inflammatory
      processes. In addition, there is increasing evidence that interactions between
      complement and coagulation provide a link between inflammation and thrombosis. On
      the other hand, the complement system also has an atheroprotective function
      through the clearance of apoptotic material.  The knowledge of these complex
      mechanisms will become increasingly important, also for clinicians, since it may
      lead to novel therapeutic and diagnostic options. Therapies targeting the
      complement system have the potential to reduce tissue damage caused by acute
      ischaemic events. Whether early anti-inflammatory and anti-complement therapy may
      be able to prevent atherosclerosis, remains a hot topic for research.

PMID- 22392003
TI  - Ring-size controllable metallamacrocycles as building blocks for the construction
      of microporous metal-organic frameworks.
AB  - Presented here is a new strategy for the synthesis of metallamacrocycles (MC[n])
      with different ring-size and guest selectivity via integrating a flexible
      trinuclear metal unit and a bridging organic ligand, and further body-centered
      cubic packing of these MCs results in the formation of three microporous MOFs for
      potential application in gas storage.

PMID- 22392004
TI  - Risk from winter vegetables and pulses produced in arsenic endemic areas of Nadia
      District: field study comparison with market basket survey.
AB  - Arsenic contaminated groundwater uses for irrigation potentially lead the
      incidence of arsenic into food chain. In present study we examined total arsenic
      concentrations in 32 types of vegetables and 7 types of pulses. Range of total
      arsenic concentration in edible parts of vegetables collected from grown fields
      was 0.114-0.910 mg/kg. Highest arsenic values were in spinach 0.910 mg/kg.
      Vegetable samples were grouped into leafy, non-leafy-fruity, root-tubers. 18
      common types of vegetables and pulses were collected through market basket
      survey, total arsenic were approximately 100 mg lower than those observed for the
      vegetables collected from the fields.

PMID- 22392005
TI  - Glyphosate, alachor and maleic hydrazide have genotoxic effect on Trigonella
      foenum-graecum L.
AB  - In the present study effects of herbicides glyphosate (GP), alachlor (AL) and
      maleic hydrazide (MH) is studied on mitotic cells of Trigonella foenum-graecum L.
      Seeds of T. foenum-graecum L. treated with a series of concentrations ranging
      from 0.1%, 0.2%, 0.3%, 0.4% and 0.5% for 1, 2 and 6 h and their effect on mitotic
      index and chromosomal aberrations was studied. The results indicate that these
      herbicides reduced mitotic index in dose-dependent manner. In addition, increase
      in the percentage of abnormal mitotic plates was observed in herbicide treated
      groups which was both concentration and time dependent. Commonly observed
      abnormalities were c-mitosis, laggards, bridges, stickiness, c-anaphase,
      precocious separation, un-equal distribution and fragments. The result of the
      present investigation indicates that commonly used herbicides GP, AL and MH have
      significant genotoxic effect on T. foenum-graecum plant.

PMID- 22392006
TI  - Histopathological effects of carbaryl on digestive system of snake-eyed lizard,
      Ophisops elegans.
AB  - We examined the effects of carbaryl in the digestive system of Ophisops elegans.
      Lizards were exposed once to different concentrations of carbaryl (2.5, 25 and
      250 MUg/g). After 96 h, findings related to the esophagus in all treatment groups
      were not conspicuous. The most important histological defects were observed in
      the stomach. In the small intestine, collapse of villi was prominent at high
      dose. In the large intestine, disintegration in epithelial cells and scattered
      secretory granules of goblet cells were observed at high dose.

PMID- 22392007
TI  - A preliminary study of total petrogenic hydrocarbon distribution in Setiu
      Wetland, southern South China Sea (Malaysia).
AB  - The distribution of total petrogenic hydrocarbon was investigated in the
      subsurface water of Setiu Wetland from July to October 2008. The concentration
      was quantified by UV-fluorescence spectroscopy and ranged from 4 to 121 MUg/L
      (mean 60 +/- 41 MUg/L). Higher total petrogenic hydrocarbon concentrations were
      found in area with high boating activities suggesting that the contribution is
      likely related to fossil fuel combustion. The present study also revealed that
      the total petrogenic hydrocarbon values are still lower that those reported in
      Malaysian coastal waters.

PMID- 22392008
TI  - Dissipation kinetics of metalaxyl in cucumber.
AB  - Residues of metalaxyl were estimated in cucumber fruits using Gas Liquid
      Chromatography (GLC) with Nitrogen phosphorus detector (NPD). Following three
      applications of Ridomil-MZ @ 0.3% and 0.6%, the average initial deposits of
      metalaxyl were observed to be 0.19 and 0.24 mg kg(-1), respectively. The residues
      dissipated below the limit of quantification (LOQ) of 0.02 mg kg(-1) after 10
      days at both the dosages. The half-life values (T(1/2)) of metalaxyl was worked
      out to be 3.5 and 3.0 days, respectively at 0.3% and 0.6% concentration. Thus, a
      waiting period of 1 day was suggested for the safe consumption of metalaxyl
      treated cucumber.

PMID- 22392009
TI  - Behavioural treatment increases activity in the cognitive neuronal networks in
      children with attention deficit/hyperactivity disorder.
AB  - Response cost and token approach (RCT) within the scope of a summer camp training
      is an effective treatment program for attention deficit hyperactivity disorder
      (ADHD). It is likely that intensive RCT training influences networks responsible
      for ADHD symptoms. Functional magnetic resonance imaging (fMRI) was carried out
      in 12 children with ADHD before and after the RCT program and in 12 healthy
      control children twice. For fMRI, a Go/No-go paradigm was used to investigate the
      influence of RCT training on attention and impulsivity. The No-go condition
      revealed only weak activation in the dorsal part of the anterior cingulate cortex
      (ACC), parietal and dorsolateral prefrontal cortex (DLPFC) before the training in
      children with ADHD compared to healthy children. However, this activation in
      these brain regions was significantly more pronounced after the training. This
      increase in hemodynamic response cannot be attributed merely to repetition of the
      measurement since the effect was not observed in healthy children. The increase
      in hemodynamic response in the ACC and right DLPFC was significantly associated
      with a reduction in response time variability and clinical symptoms in ADHD
      patients. After the RCT training, the children with ADHD demonstrated more
      pronounced activation of cortical structures which are typically related to
      response monitoring and self-control. It seems likely that children with ADHD
      learned more cognitive control in a continuous performance task as was revealed
      by both neuropsychological outcome and fMRI.

PMID- 22392010
TI  - Interleukin-1 and tumor necrosis factor alpha blockade treatment of experimental
      polymyositis in mice.
AB  - OBJECTIVE: Histologic studies of the muscles suggest that cytokines are involved
      in inflammatory myopathy. The therapeutic effects of cytokine blockade are
      controversial, with anecdotal reports of clinical efficacy. The aim of this study
      was to discern the significance of interleukin-1 (IL-1) and tumor necrosis factor
      alpha (TNFalpha) as therapeutic targets in polymyositis (PM) by studying their
      involvement and the effects of their blockade in C protein-induced myositis
      (CIM), a murine model of PM. METHODS: C57BL/6 mice were immunized with
      recombinant skeletal C protein fragments to induce CIM. The expression of IL-1
      and TNFalpha in the muscles of mice with CIM was detected using
      immunohistochemical and real-time polymerase chain reaction analyses. After the
      onset of myositis, the mice with CIM were treated with recombinant IL-1 receptor
      antagonist (IL-1Ra), anti-IL-1R monoclonal antibody, recombinant TNF receptor
      (p75)-fusion protein (TNFR-Fc), or anti-TNFalpha monoclonal antibody. The muscles
      were examined histologically for the severity of myositis. RESULTS: IL-1alpha-
      and TNFalpha-positive macrophages were observed in the muscle tissue of mice with
      CIM as early as 7 days after immunization. IL-1alpha, IL-1beta, and TNFalpha
      expression in the muscles increased as the severity of myositis peaked, at both
      the messenger RNA and protein levels. Continuous subcutaneous delivery of IL-1Ra
      resulted in suppression of established CIM. Intermittent delivery (1-day
      intervals) of anti-IL-1R monoclonal antibody suppressed myositis, while
      intermittent delivery of IL-1Ra did not suppress myositis. Treatment with anti
      TNFalpha monoclonal antibody and with TNFR-Fc also reduced the severity of CIM.
      CONCLUSION: IL-1 and TNF blockade ameliorated CIM after disease onset and should
      potentially be a new strategy for the treatment of inflammatory myopathy. As IL-1
      blockade, treatment with anti-IL-1R monoclonal antibody appeared more feasible
      than the other approaches.

PMID- 22392012
TI  - Obesity and the risk for premenopausal and postmenopausal breast cancer.
AB  - Obesity has been consistently associated with an increased risk of postmenopausal
      breast cancer in population-based studies. Conversely, obesity in such studies
      has been inversely associated with premenopausal breast cancer risk. In a report
      of data from two large chemoprevention trials, both of which enrolled women at a
      high risk of breast cancer, obesity was associated with only a modest,
      nonsignificantly increased risk of postmenopausal breast cancer and a surprising
      statistically significant 70% increased risk of premenopausal breast cancer (vs.
      normal weight). The discrepancies between these results and those from previous
      observational studies may be due to differences in study design and exposure
      ascertainment or due to inherent biologic differences whereby the obesity-breast
      cancer association differs for high-risk women in the clinical setting compared
      with general population, average-risk women in the observational setting.

PMID- 22392011
TI  - MR imaging of subscapularis tendon injury in the setting of anterior shoulder
      dislocation.
AB  - OBJECTIVE: To evaluate the degree and location patterns of subscapularis tendon
      injury in patients with prior anterior shoulder dislocation (ASD). MATERIAL AND
      METHODS: Forty-five consecutive MR shoulder examinations in patients with a
      history of ASD and 20 consecutive MR examinations in patients without prior
      dislocation were reviewed. Two readers assessed for the presence and location of
      tendinosis and tearing in the subscapularis tendon, which was divided into three
      segments: superior, middle, and inferior. The readers also documented the
      presence of anterior labral tears, osseous Bankart defects and Hill-Sachs
      lesions. Fisher's exact tests were performed to analyze the different types of
      pathology and their locations. RESULTS: Subscapularis tendinosis, and partial
      thickness and full thickness tears were more common in patients with a history of
      ASD. Tendinosis was found in 60-64.4% of the dislocation patients compared with
      40% of the non-dislocation group. When stratified by location, the middle and
      inferior thirds were the most commonly affected with statistical significance (p
      < 0.05) found in tearing of the inferior third. Anterior labral tears, osseous
      Bankart defects, and Hill-Sachs lesions were more common in the dislocation group
      with statistically significant associations with tendinosis in the middle and
      inferior thirds and tearing of the middle third (p < 0.05). CONCLUSION: Our study
      suggests an association between middle and inferior subscapularis tendon
      pathology and prior anterior shoulder dislocation. Based on our results, careful
      MR assessment of the subscapularis tendon by the radiologist is indicated in the
      setting of ASD as injury of this structure can be symptomatic and may be amenable
      to treatment.

PMID- 22392013
TI  - Magnetic resonance fluid dynamics for intracranial aneurysms--comparison with
      computed fluid dynamics.
AB  - BACKGROUND: Hemodynamics in intracranial aneurysms is thought to play an
      important role in their growth and rupture. Usual computed fluid dynamics (CFD)
      based on three-dimensional (3D) computed tomographic (CT) angiography requires a
      time-consuming process for analysis. Magnetic resonance fluid dynamics (MRFD)
      based on MR images is a new tool for analyzing flow dynamics and a promising
      method for obtaining such information more easily. We compared the data from MRFD
      and CFD and studied the clinical feasibility of MRFD. METHODS: A total of 15
      aneurysms, including two ruptured ones, in 15 patients were investigated with MR
      imaging and 3D-CT angiography. The flow data of MRFD and CFD, 3D stream lines,
      flow velocity profile and wall shear stress (WSS) were extracted from the image
      reconstruction and were compared each other. RESULTS: Both flow dynamics images
      showed quite similar 3D flow pattern and WSS map. However, the calculated value
      of maximum WSS was quite different and there was no significant correlation.
      Further, in one ruptured case, CFD showed less visualization to evaluate the
      intra-aneurysmal flow. Interestingly, one delayed rupture case showed a
      particular flow pattern with abnormal secondary flow in the bottom of the
      aneurysm before rupture, which might suggest the specific finding of rupture
      risk. CONCLUSION: MRFD is a valuable and less invasive tool to evaluate
      aneurysmal fluid dynamics. It can be obtained from the usual MRI examination
      without contrast medium and exposure to radiation. Although there is a problem of
      consistency of the absolute value of WSS between MRFD and conventional CFD, it
      may be useful to predict the risk of enlargement or rupture of aneurysms based on
      the information of the similar distribution of WSS and flow patterns. The
      quantifiable analysis and establishment of a meaningful threshold for high risk
      should be further studied.

PMID- 22392014
TI  - Vascular compression of the cochlear nerve and tinnitus: a pathophysiological
      investigation.
AB  - OBJECTIVE: Chronic microvascular compressions of the eighth nerve induce a
      slowing down of signal transmission in the auditory nerve, electrophysiologically
      characterized by IPL I-III prolongation. METHODS: The authors hypothesize this is
      compensated by an active slowing down of signal transmission of the contralateral
      input at the level of the brainstem, characterized by contralateral IPL III-V
      prolongation. RESULTS: Differences between ipsilateral and contralateral IPL I
      III and IPL III-V are analyzed before and after microvascular decompression. ABR
      diagnostic criteria for microvascular compression are ipsilateral IPL I-III
      prolongation or ipsilateral peak II decrease + ipsilateral IPL I-III
      prolongation. With IPL I-III as diagnostic criterion, unlike preoperatively the
      difference between the ipsi- and contralateral IPL I-III is significant
      postoperatively. When using the stricter diagnostic criterion of IPL I-III + peak
      II, there is a preoperative significant difference between ipsi- and
      contralateral IPL I-III, but postoperatively the difference between the ipsi- and
      contralateral IPL I-III is not significant. CONCLUSIONS: Preoperatively, there is
      a marginal significant difference between the ipsi- and contralateral IPL III-V,
      which disappears postoperatively.

PMID- 22392015
TI  - Bilateral chronic subdural non-traumatic hematoma associated with von
      Willebrand's type I disease: a case report.

PMID- 22392016
TI  - Management of bilateral trigeminal neuralgia with trigeminal radiofrequency
      rhizotomy: a treatment strategy for the life-long disease.
AB  - BACKGROUND: The objective of this study was to evaluate the effectiveness of
      percutaneous controlled radiofrequency trigeminal rhizotomy (RF-TR) in patients
      with bilateral trigeminal neuralgia (BTN). Patients were analyzed after RF-TR in
      terms of outcome, safety and complications. METHODS: Eighty-nine BTN patients
      underwent 186 RF-TR procedures. Eighty-seven patients had idiopathic trigeminal
      neuralgia (ITN) and two patients had multiple sclerosis (2.2%). Fifty-six (62.9%)
      were women and 33 (37.1%) were men. Ages ranged from 29 to 85 years. Anesthesia
      was administered at a determined optimal level, allowing patient cooperation for
      controlled and selective lesioning. RESULTS: The mean follow-up period was 101.71
      +/- 77.7 months. Familial occurrence was seen in two (2.2%) patients.
      Synchronized pain was observed in 25 (28.2%) patients. Pain occurrence on the
      contralateral side was observed with an average duration of 124.7 +/- 87.13
      months. Fifty-four of the 89 patients underwent 146 RF-TR procedures for both
      sides and 35 underwent 40 RF-TR procedures for one side. Complete pain relief or
      partial satisfactory pain relief was achieved on the medically treated side in 35
      patients. During follow-up, 36 patients required the second procedure and 7
      required the third procedure. Acute pain relief was reported in 86 (96.6%)
      patients. Early (<6 months) pain recurrence was observed in 11 (12.3%) and late
      (>6 months) recurrence in 25 (28.0%) patients. Complications included diminished
      corneal reflex in four (2.1%) patients, keratitis in two (1.1%), masseter
      dysfunction in four (2.1%), dysesthesia in two (1.1%), and anesthesia dolorosa in
      one (0.5%). CONCLUSIONS: RF-TR is an effective, selective, well-controlled, and
      effortlessly repeatable procedure for treating BTN, especially in the elderly, in
      terms of low morbidity and mortality rates and high rate of satisfactory pain
      relief.

PMID- 22392017
TI  - A healed bony puzzle: an old gunshot wound to the head.

PMID- 22392018
TI  - Quality of photographic images provided for injury interpretation: room for
      improvement?
AB  - The aim of the study was to determine the quality and nature of photographic
      images submitted to the National Injuries Database (part of the National Policing
      Improvement Agency) in the United Kingdom, for expert assessment and
      interpretation. A prospective analysis of cases (n = 50) were assessed for the
      number, origin, type and quality of images. Of 1,332 images in 50 cases submitted
      to the National Injuries Database, only 24% were appropriately labeled with an
      index; 5% were unfocussed; 64% had no rules or measurement scales; 0% had color
      charts or bars; 1.3% were of unidentifiable parts of the anatomy. The images sent
      to the National Injuries Database for interpretation originated from a variety of
      sources with no consistency in presentation. In particular, features such as
      rules or scales, color charts and appropriate labels with indexes, were absent in
      a variable number of cases, although these factors may at times be crucial to
      interpretation. It would be appropriate for standards to be developed and used
      for consistency in image capture, presentation and reproduction for
      interpretation for court settings in order to improve the quality of evidence
      available.

PMID- 22392019
TI  - Postmortem CT investigation of skeletal and dental maturation of the fetuses and
      newborn infants: a serial case study.
AB  - Physical maturation involving bones and teeth is a classic indication of fetal
      maturity in forensic practice, for which radiological examination is effective.
      The present study preliminarily investigated the efficacy of postmortem computed
      tomography (PM-CT) in estimating the gestational age of fetuses (n = 3) and
      newborn infants (n = 4), compared with plain radiography. Body length and weight
      estimated in reconstructed CT images approximated the measured values, providing
      additional data of body mass volume and fat development. The diaphyses of humerus
      and femur, and the epiphyseal ossification centers of femur and calcaneus were
      more easily identified and accurately measured in CT images than in plain
      radiographs. The developmental stage of deciduous teeth was also clearly
      identified. PM-CT was useful to evaluate the physical maturity of infants.

PMID- 22392020
TI  - First report of chronic implant-related septic arthritis and osteomyelitis due to
      Kytococcus schroeteri and a review of human K. schroeteri infections.
AB  - We report the first case of Kytococcus schroeteri implant-related septic
      arthritis and osteomyelitis, identified by phenotypic tests and 16S rRNA
      sequencing, which responded to implant removal and doxycycline. 16S rRNA
      sequencing was useful for the accurate and rapid identification of the organism
      as it exhibited three different colonial morphologies in vitro.

PMID- 22392021
TI  - Evidence of genetic segregation in the apogamous fern species Cyrtomium fortunei
      (Dryopteridaceae).
AB  - In apogamous ferns, all offspring from a parent are expected to be clonal.
      However, apogamous 'species' frequently demonstrate a large amount of
      morphological and genetic variations. Cyrtomium fortunei composed of four
      varieties (C. fortunei var. fortunei, var. clivicola, var. intermedium, and var.
      atropunctatum), is all reported to be apogamous triploids, but demonstrates large
      and continuous morphological variation. In previous studies, we showed that
      considerable genetic diversity was observed in many local populations of the
      apogamous fern 'species'. We hypothesized that genetic segregation has occurred,
      because neither sexual type nor intraspecific polyploidy have been observed in C.
      fortunei in Japan. Of 732 progeny examined (250 gametophytes and 482
      sporophytes), obtained from a parental sporophyte whose pgiC genotype was
      estimated as aab, 11 (4.4%) gametophytes and 8 (1.7%) sporophytes showed a
      different genotype (aaa) from that of the parent sporophyte. We showed that
      genetic segregation occurs in apogamous C. fortunei in relatively high frequency.
      Moreover, we could first show that the segregation frequency in gametophytes is
      significantly higher than that in sporophytes of the next generation (chi2 =
      4.90, P = 0.027). It may suggest the existence of deleterious genes, which are
      expressed during the morphogenesis and growth of sporophytes.

PMID- 22392022
TI  - First-line treatment with capecitabine combined with irinotecan in patients with
      advanced colorectal carcinoma: a phase II study.
AB  - GOALS: To evaluate the efficacy and toxicity of capecitabine with irinotecan as
      first-line treatment in metastatic colorectal cancer. BACKGROUND: The addition of
      irinotecan to infusional 5 fluorouracil and leucovorin significantly improves the
      response rate and survival compared with 5 fluorouracil/leucovorin alone in
      metastatic colorectal cancer. Capecitabine with irinoteacan was reported to yield
      comparable results in phase II studies. STUDY: Patients older than 75 years,
      Eastern Cooperative Oncology Group <=0 to 3, with measurable disease, no previous
      treatment for advanced disease, previous adjuvant chemotherapy >6 months, and
      adequate hepatic, renal, and hematological function were included. The treatment
      protocol included capecitabine 1000 mg/m twice daily given for 14 days (days 1 to
      14) and irinotecan (100 mg/m) given on days 1 and 8. Treatment was repeated on
      day 21. RESULTS: Thirty patients were included. All were assessable for response
      and toxicity. Average age was 64 years, male/female ratio 20/10. Fifteen had
      liver metastases; 9 had abdominal metastases; 5 had liver and lymph nodes
      metastases; and 1 had lung metastases. The median number of cycles was 8. Grades
      III and IV diarrheas were observed in 20%, mild vomiting in 20%, grades III and
      IV leukopenia in 23%, and hand and foot syndrome grade III in 1 patient (3%). A
      complete response was achieved in 3 (10%) patients, a partial response in 16
      (53%), disease stabilization in 6 (20%), and tumor progression in 5 (17%).
      Progression-free survival was 8.4 months. Overall survival was 19.3 months.
      CONCLUSIONS: This regimen was provided on an outpatient basis with significant
      antitumor activity and without the need for indwelling catheters and seems to be
      feasible for patients of all ages, with acceptable toxicity.

PMID- 22392023
TI  - No helicobacter left behind: detecting the infection in patients with partial
      gastrectomy.

PMID- 22392024
TI  - Epstein-Barr virus-associated gastric carcinoma: a newly defined entity.
AB  - Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a recently
      recognized entity, which is defined by the presence of EBV in the gastric
      carcinoma cells. EBVaGC represents about 10% of gastric carcinoma worldwide, and
      >80,000 patients are estimated to develop EBVaGC annually. EBVaGC shows some
      distinct clinicopathologic characteristics, such as male predominance,
      predisposition to the proximal stomach, and a high proportion in diffuse-type
      gastric carcinomas. Besides, EBVaGC also shows characteristic molecular
      abnormality, that is, global and nonrandom CpG-island methylation of the promoter
      region of many cancer-related genes, which causes downregulation of their
      expression. Moreover, EBVaGC has a relative favorable prognosis. The uniform
      presence of EBV-encoded small RNA in tumor cells but not in the surrounding
      normal epithelial cells, and the detection of monoclonal EBV episomes in EBVaGC,
      strongly suggests that EBV play an etiological role in gastric carcinogenesis.
      Therefore, EBVaGC should be regarded as a distinct entity of gastric carcinoma,
      although it only accounts for a relatively small fraction of total gastric
      carcinomas. In this review, the epidemiological and clinicopathologic features of
      EBVaGC and the genetic abnormalities of EBVaGC cell including chromosomal and
      epigenetic abnormalities are described. The roles of EBV in gastric
      carcinogenesis are discussed. We make an emphasis on the EBV latency pattern and
      genome polymorphisms as well as local immunity in EBVaGC. In addition, the
      treatment of EBVaGC is also briefly discussed. Taken together, this review aims
      to give the reader a full understanding of a newly defined entity of gastric
      carcinoma, EBVaGC.

PMID- 22392025
TI  - Diagnostic performance of urea breath test, rapid urea test, and histology for
      Helicobacter pylori infection in patients with partial gastrectomy: a meta
      analysis.
AB  - BACKGROUND: Helicobacter pylori infection has been implicated in the pathogenesis
      of gastroduodenal diseases such as recurrent peptic ulceration and particularly
      residual stomach cancer in the postoperative stomach. AIM: To determine the
      performance of different commonly used tests for the diagnosis of H. pylori
      infection in patients after partial gastrectomy. METHODS: A systematic literature
      search was conducted by searching the PubMed, EMBASE and ScienceDirect databases
      with relevant key words. Data extraction was independently performed by two
      reviewers. Meta-analyses were performed for the performance of the different
      tests including the sensitivities, specificities, likelihood ratios (LRs),
      diagnostic odds ratio diagnostic odds ratio, and the summary receiver operating
      characteristic summary receiver operating characteristic curve. The meta-analysis
      was performed by Meta-DiSc software. RESULTS: Studies showed a high degree of
      heterogeneity. Pooled sensitivity, specificity, LR+, LR- and diagnostic odds
      ratio for the different methods were: Urea breath test (9 studies): 0.77 (95% CI,
      0.72-0.82), 0.89 (95% CI, 0.85-0.93), 6.32 (95% CI, 3.22-12.42), 0.27 (95% CI,
      0.17-0.43), and 27.86 (95% CI, 13.27-58.49). Rapid urease test (7 studies): 0.79
      (95% CI, 0.72-0.84), 0.94 (95% CI, 0.90-0.97), 10.21 (95% CI, 5.94-17.54), 0.28
      (95% CI, 0.22-0.36) and 49.02 (95% CI, 24.24-99.14). Histology (3 studies): 0.93
      (95% CI, 0.88-0.97), 0.85 (95% CI, 0.73-0.93), 5.88 (95% CI, 3.26-10.60), 0.09
      (95% CI, 0.05- 0.15), and 97.28 (95% CI, 34.30-275.95). The corresponding summary
      receiver operating characteristic curves showed areas under the curves of 0.91,
      0.93 and 0.96 and Q* values of 0.84, 0.86 and 0.91, respectively CONCLUSION:
      Among the three commonly used tests, histological examination performs the best,
      followed by the rapid urease test, for the diagnosis of H. pylori infection after
      partial gastrectomy. Thus, histology, preferably after the rapid urease test, is
      recommended for the diagnosis of H. pylori infection after partial gastrectomy.

PMID- 22392026
TI  - Gastro-Antalya 2011: a successful regional meeting between the WGO and the TSG.

PMID- 22392027
TI  - A smart porphyrin cage for recognizing azide anions.
AB  - A smart porphyrin cage that can recognize azide anions by the changes of (1)H NMR
      spectra was synthesized by CuAAC "click" reaction in high yield.

PMID- 22392028
TI  - Accuracy of non-invasive blood pressure monitoring in very preterm infants.
AB  - PURPOSE: Blood pressure (BP) monitoring is an essential procedure in intensive
      care. There is controversy about the reliability of non-invasive BP measurements
      in very preterm infants. This prospective trial compared non-invasive BP
      monitoring with BP monitoring via an umbilical arterial catheter (UAC) in this
      population. METHODS: Preterm infants born at less than 32 weeks gestation
      requiring a UAC for clinical management were eligible. Enrolled infants had up to
      three BP measurements on the right arm (RA) and right leg (RL) when in a resting
      state. UAC-BP measurements were noted immediately after the non-invasive BP was
      displayed on the monitor. Measurements were analysed in subgroups according to
      birth weight: no greater than 750 g, 751-1,000 g, above 1,000 g. Statistical
      analysis reports median, range, and Bland-Altman analysis. RESULTS: Sixty infants
      were included. Median (range) gestational age was 26.4 weeks (23.6, 31.2); birth
      weight 924 g (581, 1,518). A total of 1,865 measurements were performed (RA: 935,
      RL: 930). Mean difference (95% limits of agreement) for infants no greater than
      750 g: RA 2.53 mmHg (-11.18, 16.24), RL -0.804 mmHg (-12.65, 11.04); for infants
      751-1,000 g: RA 3.535 mmHg (-9.6, 16.7), RL -1.239 mmHg (-13.14, 10.66); for
      infants above 1,000 g: RA -1.65 mmHg (-13.47, 10.17), RL -4.101 mmHg (-14.17,
      5.96). CONCLUSIONS: Although the average differences between invasive and non
      invasive BP measurements are acceptable, the range of under- and overestimation
      of non-invasive BP measurements is large and not consistent, making reliance on
      non-invasive modalities to guide circulatory management problematic. If arterial
      BP monitoring is not available, our results suggest measuring non-invasive BP on
      the leg in preterm infants with a birth weight no greater than 1,000 g.

PMID- 22392029
TI  - Dismissal of the utility of free cortisol measurement is premature.

PMID- 22392031
TI  - International evidence-based recommendations for point-of-care lung ultrasound.
AB  - BACKGROUND: The purpose of this study is to provide evidence-based and expert
      consensus recommendations for lung ultrasound with focus on emergency and
      critical care settings. METHODS: A multidisciplinary panel of 28 experts from
      eight countries was involved. Literature was reviewed from January 1966 to June
      2011. Consensus members searched multiple databases including Pubmed, Medline,
      OVID, Embase, and others. The process used to develop these evidence-based
      recommendations involved two phases: determining the level of quality of evidence
      and developing the recommendation. The quality of evidence is assessed by the
      grading of recommendation, assessment, development, and evaluation (GRADE)
      method. However, the GRADE system does not enforce a specific method on how the
      panel should reach decisions during the consensus process. Our methodology
      committee decided to utilize the RAND appropriateness method for panel judgment
      and decisions/consensus. RESULTS: Seventy-three proposed statements were examined
      and discussed in three conferences held in Bologna, Pisa, and Rome. Each
      conference included two rounds of face-to-face modified Delphi technique.
      Anonymous panel voting followed each round. The panel did not reach an agreement
      and therefore did not adopt any recommendations for six statements.
      Weak/conditional recommendations were made for 2 statements, and strong
      recommendations were made for the remaining 65 statements. The statements were
      then recategorized and grouped to their current format. Internal and external
      peer-review processes took place before submission of the recommendations.
      Updates will occur at least every 4 years or whenever significant major changes
      in evidence appear. CONCLUSIONS: This document reflects the overall results of
      the first consensus conference on "point-of-care" lung ultrasound. Statements
      were discussed and elaborated by experts who published the vast majority of
      papers on clinical use of lung ultrasound in the last 20 years. Recommendations
      were produced to guide implementation, development, and standardization of lung
      ultrasound in all relevant settings.

PMID- 22392032
TI  - Interfaces for long-term noninvasive positive pressure ventilation in children.
AB  - OBJECTIVE: The aim of the study was to report the type and tolerance of the
      interface chosen for long-term noninvasive positive pressure ventilation (NPPV)
      in children. METHODS: This was a descriptive study carried out in the clinical
      setting of a pediatric university hospital in which all children started on long
      term NPPV over a 18-month period were included. RESULTS: NPPV was started in 97
      children with neuromuscular disease or thoracic scoliosis (n = 35), obstructive
      sleep apnea with (n = 32) or without (n = 21) maxillofacial deformity, or lung
      disease (n = 9). All 25 children <= 2 years of age, as well as four older
      children, were fitted with custom-made nasal masks; all other children were
      fitted with an industrial nasal mask (50%), a facial mask (16%), or nasal prongs
      (2%). Industrial masks with and without manufactured leaks were used in 33 (34%)
      and 35 (36%) children, respectively. All patients with obstructive sleep apnea
      used interfaces with manufactured leaks, whereas all patients with neuromuscular
      disease or thoracic scoliosis used interfaces without manufactured leaks. Both
      types of interfaces were used in patients with lung disease. The interface had to
      be changed in 20 patients because of discomfort (n = 16), leaks (n = 4), facial
      growth (n = 3), skin injury (n = 2), or change of the ventilatory mode (n = 2). A
      second or third mask change was necessary in nine and four patients,
      respectively. CONCLUSION: The choice of the interface for NPPV in children is
      determined by the patient's age and the underlying disease. Discomfort is the
      main reason for mask change.

PMID- 22392033
TI  - Managing sensitive phenotypic data and biomaterial in large-scale collaborative
      psychiatric genetic research projects: practical considerations.
AB  - Large-scale collaborative research will be a hallmark of future psychiatric
      genetic research. Ideally, both academic and non-academic institutions should be
      able to participate in such collaborations to allow for the establishment of very
      large samples in a straightforward manner. Any such endeavor requires an easy-to
      implement information technology (IT) framework. Here we present the requirements
      for a centralized framework and describe how they can be met through a modular IT
      toolbox.

PMID- 22392034
TI  - The role of PGC-1 and Apoepsilon4 in insomnia.
AB  - OBJECTIVE: Insomnia is associated with certain psychiatric illnesses such as
      anxiety disorder and depressive disorder. Moreover, sleep is controlled by
      endogenous circadian genes, which are associated with peroxisome proliferator
      activated receptor-gamma coactivator-1alpha (PGC-1alpha). In addition,
      apolipoprotein epsilon4 (Apoepsilon4), which plays an important role in lipid
      metabolism, may be also associated with some mental disorders related to
      insomnia. The aim of this study was to investigate the role of PGC-1alpha in
      insomnia among different mental disorder groups under the control of Apoepsilon4
      and other psychosocial factors. METHODS: A total of 202 patients with insomnia
      and 253 controls were recruited. RESULTS: Logistic regression and structural
      equation modeling showed similar results in that with sex and age controlled,
      major depressive disorder, PGC-1alpha and Apoepsilon4 increased the risk of
      insomnia. With the factors of sex, age, major depressive disorder, and
      Apoepsilon4 controlled, PGC-1alpha still increased the risk for insomnia, showing
      that the GG allele of PGC-1alpha may play an important role in insomnia.
      CONCLUSION: In the future, when treating those with insomnia and high lipid
      profiles, health education with regard to how to control their lipid profile
      maybe used.

PMID- 22392036
TI  - A pilot study of serum microRNA signatures as a novel biomarker for occult
      hepatitis B virus infection.
AB  - The implementation of hepatitis B surface antigen (HBsAg) screening tests has
      significantly enhanced blood transfusion safety. However, the transmission of
      HBsAg-negative blood components can still occur in the acute phase of infection
      during the seronegative window period or during chronic stages of infection such
      as occult hepatitis virus B infection (OBI). OBI, characterized by the presence
      of HBV infection without detectable HBsAg, is capable to elude the routine
      detection with HBV serologic markers and harbor a potential risk of HBV
      transmission through blood transfusion or organ transplantation. Here, we test
      the hypothesis that OBI patients have a differentially expressed profile of
      microRNA (miRNA) in serum, and this unique serum miRNA signature can serve as a
      biomarker to detect OBI. Employing TaqMan probe-based quantitative reverse
      transcription polymerase chain reaction (qRT-PCR), we assessed the expression
      level of miRNAs in serum samples. To control for miRNA quantitation, we added an
      exogenous plant miRNA, MIR156a, into the samples before RNA extraction and used
      it as an internal control. After screening 13 previously identified HBV-specific
      serum miRNAs, we obtained four miRNAs, let-7c, miR-23b, miR-122, and miR-150,
      which are differentially expressed in OBI sera compared to healthy control sera.
      This 4-serum miRNA signature shows a high level of accuracy in discriminating
      both OBI (AUC = 0.999) and HBV (AUC = 0.989) cases from the non-infected
      controls. Cluster analysis also demonstrates that this 4-miRNA signature can
      clearly separate OBI patients from the control group. Our results demonstrate for
      the first time that a profile of serum miRNAs can serve as a sensitive and
      accurate biomarker for OBI detection.

PMID- 22392042
TI  - Breast cancer phenotype in women with TP53 germline mutations: a Li-Fraumeni
      syndrome consortium effort.
AB  - Breast cancer is the most common tumor in women with Li-Fraumeni Syndrome (LFS),
      an inherited cancer syndrome associated with germline mutations in the TP53 tumor
      suppressor gene. Their lifetime breast cancer risk is 49% by age 60. Breast
      cancers in TP53 mutation carriers recently have more often been reported to be
      hormone receptor and HER-2 positive by immunohistochemistry and FISH in small
      series. We seek to complement the existing small literature with this report of a
      histopathologic analysis of breast cancers from women with documented LFS.
      Unstained slides and paraffin-embedded tumor blocks from breast cancers from 39
      germline TP53 mutation carriers were assembled from investigators in the LFS
      consortium. Central histology review was performed on 93% of the specimens by a
      single breast pathologist from a major university hospital. Histology, grade, and
      hormone receptor status were assessed by immunohistochemistry; HER-2 status was
      defined by immunohistochemistry and/or FISH. The 43 tumors from 39 women comprise
      32 invasive ductal carcinomas and 11 ductal carcinomas in situ (DCIS). No other
      histologies were observed. The median age at diagnosis was 32 years (range 22
      46). Of the invasive cancers, 84% were positive for ER and/or PR; and 81% were
      high grade. Sixty three percent of invasive and 73% of in situ carcinomas were
      positive for Her2/neu (IHC 3+ or FISH amplified). Of the invasive tumors, 53%
      were positive for both ER and HER2+; other ER/PR/HER2 combinations were observed.
      The DCIS were positive for ER and HER2 in 27% of the cases. This report of the
      phenotype of breast cancers from women with LFS nearly doubles the literature on
      this topic. Most DCIS and invasive ductal carcinomas in LFS are hormone receptor
      positive and/or HER-2 positive. These findings suggest that modern treatments may
      result in improved outcomes for women with LFS-associated breast cancer.

PMID- 22392043
TI  - Biologic features and prognosis of ductal carcinoma in situ are not adversely
      impacted by initial large body mass.
AB  - Obesity is associated with adverse biologic features and poor outcome in patients
      with invasive breast cancer, yet this relationship has not been evaluated in
      patients with ductal carcinoma in situ (DCIS). From 1996 to 2009, body mass index
      (BMI) was recorded at initial diagnosis for 1,885 patients with DCIS treated at
      our institution. Patients were categorized as obese (BMI >= 30 kg/m(2)),
      overweight (BMI 25 to <30 kg/m(2)), or of normal weight or underweight (BMI < 25
      kg/m(2)). Logistic regression was used to examine associations between BMI and
      patient, clinical, and pathologic features and treatment. Local-regional
      recurrence was calculated using the Kaplan-Meier method. All statistical tests
      were two-sided. Of the 1,885 patients, 514 (27.7%) were obese, 510 (27.5%) were
      overweight, and 831 (44.8%) were normal/underweight. In multivariate analysis,
      overweight and obese patients were significantly more likely to be African
      American (odds ratio [OR], 3.93; 95% confidence interval [CI], 2.66-5.80) or
      Hispanic (OR, 1.44; CI, 1.02-2.04), be postmenopausal (OR, 1.63; CI, 1.28-2.07),
      have diabetes (OR, 4.60; CI, 2.60-8.12), have estrogen-receptor-positive DCIS
      (OR, 1.39; CI, 1.00-192), and present with a radiologic abnormality rather than
      clinical symptoms (OR, 1.35; CI, 1.01-1.80). At a median follow-up time of 4.96
      years (range, 1.0-14.34 years), no significant differences in local recurrence
      rates were detected based on patients' initial BMI category. Furthermore, there
      was no significant difference in risk of recurrence between diabetic patients
      receiving metformin or not. In conclusion, higher BMI is not associated with
      adverse biologic features or prognosis in patients with DCIS.

PMID- 22392044
TI  - Cross-reactive antibodies to target proteins are dependent upon oligomannose
      glycosylated epitopes in HTLV-1 associated neurological disease.
AB  - Our lab recently identified a cross-reactive antibody response between human T
      lymphotropic virus type-1-p24-(gag) (HTLV-1-p24-(gag)) and peroxiredoxin-1 (PrX
      1) as potentially contributing to the pathogenesis of HTLV-1 associated
      neurological disease via molecular mimicry. These targets proteins were
      glycosylated, yet the glycan side chains immunoreactive with the immunoglobulins
      were unknown. Using a combination of lectin isolation and serial enzymatic
      deglycosylation of glycoproteins, we determined that the immunoreactive epitopes
      contained branched oligomannose side chains. These data suggest that post
      translational glycosylation specifically related to oligomannose immunoreactivity
      to both the infecting and host antigens may contribute to molecular mimicry and
      be important in the pathogenesis of HTLV-1 associated neurological disease.

PMID- 22392045
TI  - Knockdown of core 1 beta 1, 3-galactosyltransferase prolongs skin allograft
      survival with induction of galectin-1 secretion and suppression of CD8+ T cells:
      T synthase knockdown effects on galectin-1 and CD8+ T cells.
AB  - Core 1 beta 1,3-galactosyltransferase also known as T-antigen-synthase or T
      synthase is a key enzyme for the synthesis of the common core 1 O-glycan
      structure (T-antigen). Although T-synthase is known to be important in human
      immune-related diseases, the effects of T-synthase and T-antigen on host immune
      responses remain poorly defined. In this study, a T-synthase-specific short
      hairpin RNA (shRNA) was transfected into murine colon carcinoma CT26 cells or
      mouse muscle tissues via intramuscular electroporation to assess the effects of T
      synthase on T cells and cytokines. T-synthase knockdown significantly induced
      galectin-1 secretion both in vivo and in vitro and strongly enhanced Th2 cytokine
      (IL-10 and IL-4) production in vivo. Further, the increased production of
      galectin-1 induced by T-synthase knockdown promoted CD8(+) T-cell apoptosis,
      which, when combined with the increased production of CD4(+) T cell-derived Th2
      cytokines prolonged the survival of skin allografts in mice. Our data suggest
      core 1 beta 1,3-galactosyltransferase-shRNA could serve not only as a useful tool
      in organ transplantation but also as a powerful tool for investigating O-glycans
      and glycoprotein synthesis and function.

PMID- 22392046
TI  - Safety, efficacy and pharmacokinetics of a new 10% liquid intravenous
      immunoglobulin (IVIG) in patients with primary immunodeficiency.
AB  - INTRODUCTION: An investigational 10% liquid intravenous immunoglobulin (IVIG) was
      studied in 63 patients with primary immunodeficiency (PID) at 15 study sites.
      METHODS: Patients were treated every 3 or 4 weeks with 254-1029 mg/kg/infusion of
      IVIG. RESULTS: Overall, Biotest-IVIG infusions were well tolerated. The
      proportion of infusions that were associated with adverse events during infusion,
      and up to 72 h after infusion, including those unrelated to study product, was
      27.7% with an upper 95% confidence limit <=30.6%. Two serious bacterial
      infections (SBIs) were observed resulting in a serious bacterial infection rate
      of 0.035 per person per year and an upper one-sided 99% confidence limit of
      <=0.136 SBI/patient/year. The number of days of work or school missed due to
      infection were relatively low at 2.28 days/patient/year. Two patients were
      hospitalized for infection producing a rate of 0.21 hospitalization
      days/patient/year. The IgG half-life was approximately 30 days with variation
      among individuals. CONCLUSIONS: Pharmacokinetic parameters of specific antibody
      activities were essentially the same as those of total IgG. Biotest-IVIG is safe
      and effective in the treatment of PID.

PMID- 22392047
TI  - Inflammation-induced hepcidin is associated with the development of anemia and
      coronary artery lesions in Kawasaki disease.
AB  - PURPOSE: Kawasaki disease (KD) is a systemic febrile vasculitis complicated by
      coronary artery lesions (CAL). Anemia is common in patients with KD and is
      associated with a prolonged duration of active inflammation. Hepcidin is a
      central modulator of inflammation-associated anemia, acting via control of iron
      absorption and a direct inhibitory effect on erythropoiesis. The aims of this
      study were to investigate the role of inflammation-induced hepcidin in the
      development of anemia, the occurrence of CAL formation, and IVIG treatment
      response in patients with KD. METHODS: Eighty-six KD patients and 30 febrile
      controls were enrolled. Levels of interleukin (IL)-6 and serum hepcidin were
      measured in sera by enzyme-linked immunosorbent assay. Hemoglobin and serum iron
      levels were also measured. RESULTS: Hemoglobin and iron levels were lower in KD
      patients than in controls (p < 0.001 and p = 0.009, respectively). Serum hepcidin
      and IL-6 levels were higher in KD patients than in controls (both p < 0.001)
      before intravenous immunoglobulin (IVIG) treatment. After IVIG treatment, serum
      hepcidin, IL-6, and hemoglobin levels decreased significantly (all p < 0.001). In
      addition, the serum hepcidin levels before IVIG treatment were negatively
      correlated with hemoglobin levels after IVIG treatment (R = -0.188, p = 0.046)
      and positively correlated with the changes of hemoglobin levels after IVIG
      treatment (R = 0.269, p = 0.015). Furthermore, serum hepcidin levels were
      negatively correlated with serum iron levels (R = -0.412, p = 0.002), which were
      positively correlated with hemoglobin levels (R = 0.210, p = 0.045).
      Additionally, the change of hepcidin levels was associated with IVIG treatment
      response and the occurrence of CAL formation. CONCLUSIONS: Inappropriately raised
      hepcidin levels impair iron metabolism and are associated with decreased
      hemoglobin levels in KD patients. Inflammation-induced hepcidin is associated
      with the development of anemia and disease outcomes in patients with KD.

PMID- 22392048
TI  - Apoptotic effects of a chimeric plant virus carrying a mimotope of the hepatitis
      C virus hypervariable region 1: role of caspases and endoplasmic reticulum
      stress.
AB  - The role of apoptosis in the persistence of hepatitis C virus (HCV) infection is
      controversial. Moreover, conflicting data on the modulation of this process by
      HCV proteins have been provided. We evaluated the susceptibility of peripheral
      lymphocytes from patients with chronic hepatitis C to apoptosis both spontaneous
      and after incubation with a chimeric Cucumber mosaic virus (CMV) carrying 180
      copies of the synthetic R9 mimotope obtained from more than 200 hypervariable
      region-1 sequences of HCV. Resting T lymphocytes were found to be sensitized to
      apoptosis as a result of chronic HCV infection. The plant virus-derived vector R9
      CMV displayed a strong pro-apoptotic effect associated with activation of both
      caspase-8 and -9, indicating the involvement of both extrinsic and intrinsic
      apoptotic pathways. A parallel R9-CMV-mediated activation of endoplasmic
      reticulum-stress was suggested by the significant induction of BiP/GRP78, GADD153
      and caspase-12. These data contribute to define the complex HCV/host interaction,
      and open new prospects for developing a plant-derived antigen-presenting system
      to strengthen host defences against persistent pathogens.

PMID- 22392049
TI  - Single nucleotide polymorphisms in multiple sclerosis: disease susceptibility and
      treatment response biomarkers.
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating and
      neurodegenerative disease of the central nervous system characterized by
      unpredictable and variable clinical course. Etiology of MS involves both genetic
      and environmental factors. New technologies identified genetic polymorphisms
      associated with MS susceptibility among which immunologically relevant genes are
      significantly overrepresented. Although individual genes contribute only a small
      part to MS susceptibility, they might be used as biomarkers, thus helping to
      identify accurate diagnosis, predict clinical disease course and response to
      therapy. This review focuses on recent progress in research on MS genetics with
      special emphasis on the possibility to use single nucleotide polymorphism of
      candidate genes as biomarkers of susceptibility to disease and response to
      therapy.

PMID- 22392050
TI  - The potential of interleukin-17 to mediate hematopoietic response.
AB  - It has long been known that T cells have the potential to modulate hematopoietic
      response in different ways. More recently, the importance of interleukin (IL)-17
      secreting Th17 cells in T-cell-mediated regulation of hematopoiesis was indicated
      by the line of evidence that IL-17 links T-cell function and hematopoiesis
      through stimulation of granulopoiesis and neutrophil trafficking. Furthermore,
      our data demonstrated that IL-17 also affects other cells of hematopoietic
      system, such as erythroid progenitors, as well as mesenchymal stem cells. In
      order to better understand the regulatory role of IL-17 in hematopoiesis,
      molecular mechanisms underlying the effects of IL-17 on hematopoietic and
      mesenchymal stem cells were also studied.

PMID- 22392051
TI  - The response of human dendritic cells to co-ligation of pattern-recognition
      receptors.
AB  - Dendritic cells (DCs) are key antigen-presenting cells that express a wide
      variety of pattern-recognition receptors (PRRs). Triggering of a single PRR,
      especially Toll-like receptors (TLRs) and C-type lectins, induces maturation of
      DCs, but cooperativity between multiple PRRs is needed in order to achieve an
      effective immune response. In this review, we summarize the published data
      related to the effect of individual and joint PRR agonists on DCs and Langerhans
      like cells derived from monocytes (MoDCs and MoLCs, respectively). Our results
      demonstrate that MoDCs co-stimulated with TLR3/TLR7 and TLR3/Dectin-1 ligands
      induced superior T helper (Th)1 and Th17 immune responses, compared to effects of
      single agonists. The opposite outcome was observed after co-ligation of TLR3 and
      Langerin on MoLCs. These findings may be relevant to improve strategy for tumor
      immunotherapy.

PMID- 22392052
TI  - CXCL12 in control of neuroinflammation.
AB  - Inflammation within the central nervous system (CNS) is strictly controlled and
      if possible prevented. Such a tight control is necessary due to high sensitivity
      of nervous tissue to mechanical and biochemical consequences of inflammation.
      Still, neuroinflammation is a typical feature of a chronic, inflammatory,
      demyelinating disease multiple sclerosis (MS) and its animal model experimental
      autoimmune encephalomyelitis (EAE). It is assumed that mechanisms that should
      prevent activation of immune cells at the periphery, in the lymphoid tissues,
      and/or inflammation within the CNS are inadequately efficient in MS patients.
      Here, some recent data about the importance of CXCL12 for regulation of
      neuroinflammation and contribution of its deviant expression within the CNS to
      EAE and MS pathogenesis are presented.

PMID- 22392055
TI  - Immunologic research: Publishing knowledge of the future today!: the first three
      decades.

PMID- 22392056
TI  - Multiplex amplicon quantification screening the ABCA13 gene for copy number
      variation in schizophrenia and bipolar disorder.

PMID- 22392054
TI  - Trichinella spiralis: shaping the immune response.
AB  - The co-evolution of a wide range of helminth parasites and vertebrates
      represented a constant pressure on the host's immune system and a selective force
      for shaping the immune response. Modulation of the immune system by parasites is
      accomplished partly by dendritic cells. When exposed to helminth parasites or
      their products, dendritic cells do not become classically mature and are potent
      inducers of Th2 and regulatory responses. Treating animals with helminths (eggs,
      larvae, extracts) causes dampening or in some cases prevention of allergic or
      autoimmune diseases. Trichinella spiralis (T. spiralis) possess a capacity to
      retune the immune cell repertoire, acting as a moderator of the host response not
      only to itself but also to third party antigens. In this review, we will focus on
      the ability of T. spiralis-stimulated dendritic cells to polarize the immune
      response toward Th2 and regulatory mode in vitro and in vivo and also on the
      capacity of this parasite to modulate autoimmune disease--such as experimental
      autoimmune encephalomyelitis.

PMID- 22392053
TI  - IL-33/ST2 axis in inflammation and immunopathology.
AB  - Interleukin-33 (IL-33), a member of the IL-1 family of cytokines, binds to its
      plasma membrane receptor, heterodimeric complex consisted of membrane-bound ST2L
      and IL-1R accessory protein, inducing NFkB and MAPK activation. IL-33 exists as a
      nuclear precursor and may act as an alarmin, when it is released after cell
      damage or as negative regulator of NFkappaB gene transcription, when acts in an
      intracrine manner. ST2L is expressed on several immune cells: Th2 lymphocytes,
      NK, NKT and mast cells and on cells of myeloid lineage: monocytes, dendritic
      cells and granulocytes. IL-33/ST2 axis can promote both Th1 and Th2 immune
      responses depending on the type of activated cell and microenvironment and
      cytokine network in damaged tissue. We previously described and discuss here the
      important role of IL-33/ST2 axis in experimental models of type 1 diabetes,
      experimental autoimmune encephalomyelitis, fulminant hepatitis and breast cancer.
      We found that ST2 deletion enhance the development of T cell-mediated autoimmune
      disorders, EAE and diabetes mellitus type I. Disease development was accompanied
      by dominantly Th1/Th17 immune response but also higher IL-33 production, which
      suggest that IL-33 in receptor independent manner could promote the development
      of inflammatory autoreactive T cells. IL-33/ST2 axis has protective role in Con A
      hepatitis. ST2-deficient mice had more severe hepatitis with higher influx of
      inflammatory cells in liver and dominant Th1/Th17 systemic response. Pretreatment
      of mice with IL-33 prevented Con A-induced liver damage through prevention of
      apoptosis of hepatocytes and Th2 amplification. Deletion of IL-33/ST2 axis
      enhances cytotoxicity of NK cells, production of IFN-gamma in these cells and
      systemic production of IFN-gamma, IL-17 and TNF-alpha, which leads to attenuated
      tumor growth. IL-33 treatment of tumor-bearing mice suppresses activity of NK
      cells, dendritic cell maturation and enhances alternative activation of
      macrophages. In conclusion, we observed that IL-33 has attenuated anti
      inflammatory effects in T cell-mediated responses and that both IL-33 and ST2
      could be further explored as potential therapeutic targets in treatment of immune
      mediated diseases.

PMID- 22392057
TI  - Disc herniation diagnosis in MRI using a CAD framework and a two-level
      classifier.
AB  - PURPOSE: Disc herniation in the lumbar spine is a common condition, so an
      automated method for diagnosis could be helpful in clinical applications. A
      computer-aided framework for disk herniation diagnosis was developed for use in
      magnetic resonance imaging (MRI). MATERIALS AND METHOD: A computer-aided
      diagnosis framework for lumbar spine with a two-level classification scheme for
      disc herniation diagnosis was developed using heterogeneous classifiers: a
      perceptron classifier, a least mean square classifier, a support vector machine
      classifier, and a k-Means classifier. Each classifier makes a diagnosis based on
      a feature set generated from regions of interest that contain vertebrae, a disc,
      and the spinal cord. Then, an ensemble classifier makes a final decision using
      score values of each classifier. We used clinical MR image data from 70 subjects
      in T1-weighted sagittal view and T2-weighted sagittal view for evaluation of the
      system. RESULTS: MR images of 70 subjects were processed using the proposed
      framework resulting in successful detection of disc herniation with 99% accuracy,
      achieving a speedup factor of 30 in comparison with radiologist's diagnosis.
      CONCLUSION: The computer-aided framework works well to diagnose herniated discs
      in MRI scans. We expect the framework can be adapted to effectively diagnose a
      variety of abnormalities in the lumbar spine.

PMID- 22392059
TI  - Viability analysis of multi-fishery.
AB  - This work is about the viability domain corresponding to a model of fisheries
      management. The dynamic is subject of two constraints. The biological constraint
      ensures the stock perennity where as the economic one ensures a minimum income
      for the fleets. Using the mathematical concept of viability kernel, we find out a
      viability domain which simultaneously enables the fleets to exploit the resource,
      to ensure a minimum income and stock perennity.

PMID- 22392060
TI  - Proceeding of the Third International Conference of the French-speaking Society
      for Theoretical Biology.

PMID- 22392061
TI  - Cardiomyopathies: Mutations in a big gene are linked to a big heart.

PMID- 22392058
TI  - Effects of aripiprazole and clozapine on the treatment of glycolytic carbon in
      PC12 cells.
AB  - Aripiprazole is the only atypical antipsychotic drug known to cause the
      phosphorylation of AMP-activated protein kinase (AMPK) in PC12 cells. However,
      the molecular mechanisms underlying this phosphorylation in aripiprazole-treated
      PC12 cells have not yet been clarified. Here, using PC12 cells, we show that
      these cells incubated for 24 h with aripiprazole at 50 MUM and 25 mM glucose
      underwent a decrease in their NAD+/NADH ratio. Aripiprazole suppressed cytochrome
      c oxidase (COX) activity but enhanced the activities of pyruvate dehydrogenase
      (PDH), citrate synthase and Complex I. The changes in enzyme activities coincided
      well with those in NADH, NAD+, and NAD+/NADH ratio. However, the bioenergetic
      peril judged by the lowered COX activity might not be accompanied by excessive
      occurrence of apoptotic cell death in aripiprazole-treated cells, because the
      mitochondrial membrane potential was not decreased, but rather increased. On the
      other hand, when PC12 cells were incubated for 24 h with clozapine at 50 MUM and
      25 mM glucose, the NAD+/NADH ratio did not change. Also, the COX activity was
      decreased; and the PDH activity was enhanced. These results suggest that
      aripiprazole-treated PC12 cells responded to the bioenergetic peril more
      effectively than the clozapine-treated ones to return the ATP biosynthesis back
      toward its ordinary level. This finding might be related to the fact that
      aripiprazole alone causes phosphorylation of AMPK in PC12 cells.

PMID- 22392062
TI  - Acute coronary syndromes. High uric acid levels predict mortality.

PMID- 22392063
TI  - Pharmacotherapy. Elevating HDL-cholesterol levels with dalcetrapib is safe.

PMID- 22392064
TI  - Extending the family of Zn-based MOFs: synthetic approaches to chiral framework
      structures and MOFs with large pores and channels.
AB  - Tri- and pentanuclear, kinetically stable SBUs were exploited for the preparation
      of the novel MOFs [Zn(3)(BTEB)(2)(DMF)(2)] and (Me(2)NH(2))[Zn(5)(BTEB)(3)(MU(3)
      OH)(2)(DMF)(2)]. The applied synthetic approach results in topologies that are
      stabilised by tritopic benzene-trisethynylbenzoic acid (BTEB) linkers giving rise
      to chiral frameworks with large pores or channels.

PMID- 22392065
TI  - Valsartan and telmisartan abrogate angiotensin II-induced downregulation of ABCA1
      expression via AT1 receptor, rather than AT2 receptor or PPARgamma activation.
AB  - The possible pharmacological mechanism by which partial PPARgamma-activating
      angiotensin II (Ang II) type 1 receptor blocker (ARB) telmisartan and non
      PPARgamma-activating ARB valsartan reverse Ang II-suppressed ABCA1 expression is
      still unclear. In this study, human monocyte-derived THP-1 cells were
      differentiated into macrophages. Cells were treated with various concentrations
      of Ang II alone or with Ang II and various drugs including highly selective ARB
      valsartan, partial PPARgamma-activating ARB telmisartan, angiotensin II type 2
      (AT2) receptor blocker PD123319, full PPARgamma agonist pioglitazone, and
      PPARgamma antagonist GW9662, respectively. After treatment, messenger RNA and
      protein expressions of ABCA1 and ABCG1 were analyzed by real-time polymerase
      chain reaction and Western blotting, respectively. ABCA1 expression was
      remarkably suppressed by Ang II at both messenger RNA and protein levels in a
      dose-dependent manner in THP-1-derived macrophages, whereas ABCG1 expression was
      not affected. Valsartan and telmisartan could both reverse the downregulation of
      Ang II on ABCA1 expression. Such effects were not affected by either AT2 receptor
      blocker PD123319 or PPARgamma antagonist GW9662. Our findings suggest that the
      effect of Ang II on ABCA1 expression should be mediated by the AT1 receptor. Both
      valsartan and telmisartan abrogate Ang II-induced downregulation of ABCA1
      expression mainly through AT1 receptor rather than through AT2 receptor or
      PPARgamma-dependent pathway.

PMID- 22392066
TI  - Simvastatin attenuated cerebrovascular cell proliferation in the development of
      hypertension through Rho/Rho-kinase pathway.
AB  - The cerebrovascular remodeling is a prominent feature of hypertension and
      considered as a major risk of stroke. Statins may suppress the activation of the
      Rho/Rho-kinase pathway and have pleiotropic actions against the development of
      vascular remodeling. We hypothesized that the inhibition of the Rho/Rho-kinase
      pathway by simvastatin during hypertension could recuperate the pathological
      changes of basilar artery through the downregulation of cell proliferation. To
      resolve the problem, we used 2-kid, 2-clip rat as a hypertension model and
      evaluated the effect of simvastatin on the Rho/Rho-kinase pathway. In addition,
      we assessed the changes of the proliferation rate by CCK-8 assay in basilar
      artery smooth muscle cells. Our results from this study showed that a continuous
      increase in the plasma endothelin-1 (ET-1) concentration and the Rho/Rho-kinase
      activity was positively correlated with changes in blood pressure in the
      hypertensive rat. Simvastatin ameliorated the upregulated Rho/Rho-kinase activity
      and cell proliferation during hypertension. Moreover, simvastatin, the RhoA
      inhibitor C3, and the RhoA-kinase inhibitor Y27632 all attenuated the
      proliferation rate induced by ET-1 in basilar artery smooth muscle cells via the
      Rho/Rho-kinase signaling pathway. In conclusion, simvastatin attenuated ET-1
      induced proliferation through the Rho/Rho-kinase signaling pathway in
      hypertensive rat basilar artery, and it may be an excellent reagent to protect
      vascular remodeling and stroke.

PMID- 22392067
TI  - Anterior cruciate ligament reconstruction using biodegradable transfemoral
      fixation at 5-year follow-up: clinical and magnetic resonance imaging evaluation.
AB  - PURPOSE: Biodegradable transfemoral graft fixation devices used in anterior
      cruciate ligament (ACL) reconstruction have recently been reported to
      precociously lose structural integrity. METHODS: This study investigated outcomes
      after ACL reconstruction using hamstring grafts and biodegradable transfemoral
      fixation at 5-year follow-up. The condition of both graft and fixation device was
      evaluated by magnetic resonance imaging (MRI) and related to clinical outcomes.
      In total, 85 patients on whom index ACL reconstructive surgery by means of a
      quadrupled semitendinosus-gracilis graft and biodegradable transfemoral fixation
      was performed were included in the study. RESULTS: Fifty-nine patients could be
      assessed by clinical and MRI examinations at a mean follow-up of 61 months
      (range, 52-69 months). Completely intact pins were found in 17 patients (29%),
      intact pins with delicate areas of resorption in 8 patients (14%), pin
      deformation in 5 patients (8%), pin fracture in 22 patients (37%) and pin
      migration in 3 patients (5%). In 40 patients (68%), pins had undergone
      degradation at the graft suspension point. Hamstring graft integrity and signal
      intensity scores were found to be significantly higher in patients with deformed,
      broken or dislocated pins as compared to patients with fully or mainly intact
      pins. Clinically, the mean side-to-side difference in anterior-posterior-laxity
      was 1.1 +/- 1.6 mm, while Lysholm, IKDC and Tegner scores were 89 +/- 11, 84 +/-
      14 and 4 (1-9). No statistically significant correlation was found between pin
      condition and clinical outcomes. CONCLUSION: Biodegradable fixation pins lose
      structural integrity in a way that suggests continuous loading of the pin/graft
      construct, thereby questioning osseous incorporation of the graft. This situation
      is clinically relevant in terms of improved graft condition. LEVEL OF EVIDENCE:
      Retrospective case series, Level III.

PMID- 22392068
TI  - Distal femur and proximal tibia replacement with megaprosthesis in revision knee
      arthroplasty: a limb-saving procedure.
AB  - PURPOSE: The aim of the present study was to assess whether using megaprostheses
      in revision knee arthroplasty procedures allows limb salvage with an acceptable
      outcome and complication rate, in comparison with other limb-saving procedures.
      METHODS: Between 2000 and 2010, megaprosthesis implantation was required for non
      oncologic indications in 20 patients (21 knees) (average age 73 years).
      Reconstructions involved the distal femur (n = 15), proximal tibia (n = 4), and
      both femur and tibia (n = 2). The indications, type, and numbers of previous
      operations and implants, as well as complications associated with megaprosthesis
      implantation, were reviewed, and the clinical and radiographic outcomes after an
      average follow-up period of 34 months (range 10-84 months) were evaluated.
      RESULTS: The indications for megaprosthesis implantation were periprosthetic
      infection (n = 5), fracture (n = 9), nonunion (n = 5), and aseptic loosening (n =
      2). The types of implant placed before the megaprosthetic reconstruction were a
      cemented rotating-hinge arthroplasty (n = 16) and a primary total knee
      arthroplasty (n = 5). Six patients had an additional osteosynthesis of the distal
      femur. An average of 3.8 operations (range 1-7) had been carried out before
      megaprosthesis implantation. Complications developed in 11 patients. The Knee
      Society Score improved significantly, from 43 (+/- 15) to 68 (+/- 16.8); P <
      0.05. CONCLUSIONS: Megaprosthesis implantation in revision knee arthroplasty is
      an exceptional indication. Despite the high complication rate, the patients can
      be spared amputation in most cases, and rapid mobilization with full weight
      bearing is possible.

PMID- 22392069
TI  - Whole-body FDG PET/CT is more accurate than conventional imaging for staging
      primary breast cancer patients.
AB  - PURPOSE: This retrospective study aimed (1) to compare the diagnostic accuracy of
      whole-body FDG PET/CT for initial breast cancer staging with the accuracy of a
      conventional, multimodal imaging algorithm, and (2) to assess potential
      alteration in patient management based on the FDG PET/CT findings. METHODS:
      Patients with primary breast cancer (106 women, mean age 57 +/- 13 years)
      underwent whole-body FDG PET/CT and conventional imaging (X-ray mammography, MR
      mammography, chest plain radiography, bone scintigraphy and breast, axillary and
      liver ultrasonography). The diagnostic accuracies of FDG PET/CT and a
      conventional algorithm were compared. Diagnostic accuracy was assessed in terms
      of primary tumour detection rate, correct assessment of primary lesion focality,
      T stage and the detection rates for lymph node and distant metastases.
      Histopathology, imaging or clinical follow-up served as the standards of
      reference. RESULTS: FDG PET/CT was significantly more accurate for detecting
      axillary lymph node and distant metastases (p = 0.0125 and p < 0.005,
      respectively). No significant differences were detected for other parameters.
      Synchronous tumours or locoregional extraaxillary lymph node or distant
      metastases were detected in 14 patients (13%) solely by FDG PET/CT. Management of
      15 patients (14%) was altered based on the FDG PET/CT findings, including 3
      patients with axillary lymph node metastases, 5 patients with extraaxillary lymph
      node metastases, 4 patients with distant metastases and 3 patients with
      synchronous malignancies. CONCLUSION: Full-dose, intravenous contrast-enhanced
      FDG PET/CT was more accurate than conventional imaging for initial breast cancer
      staging due to the higher detection rate of metastases and synchronous tumours,
      although the study had several limitations including a retrospective design, a
      possible selection bias and a relevant false-positive rate for the detection of
      axillary lymph node metastases. FDG PET/CT resulted in a change of treatment in a
      substantial proportion of patients.

PMID- 22392072
TI  - On the fine anatomy of the human cerebellum. 1874.

PMID- 22392071
TI  - Long-term outcome and prognostic factors after spontaneous cerebellar hemorrhage.
AB  - Cerebellar hemorrhage is the least common type of intracranial hemorrhage (ICH)
      encountered in clinical practice, and clinical data concerning the long-term
      outcomes are limited. This study aimed to investigate the long-term outcomes
      following spontaneous cerebellar hemorrhage in a cohort of Chinese patients. This
      single-center observational study was carried out between 1996 and 2010 and
      included 72 consecutive Chinese patients with a first spontaneous cerebellar
      hemorrhage. Of 440 patients with primary ICH, 72 (16.4%) had primary cerebellar
      hemorrhage. The mean age was 67.5 +/- 12.3 years and patients were predominantly
      male (54%). The 30-day mortality was 16.7% with Glasgow coma scale <= 8 as the
      only predictor. At 6 months, 56.7% of patients who survived the first 30 days had
      a persistently poor functional status with modified Rankin scale score >2. After
      a mean follow-up of 4.7 years, 3.3% of patients had recurrent ICH, a recurrence
      rate of 7.3 per 1,000 patient-years. Ischemic stroke occurred in 12% of patients,
      an incidence of 25.5 per 1,000 patient-years. This study provided data on the
      long-term outcome of post-cerebellar hemorrhage in Chinese patients.

PMID- 22392073
TI  - Improved L-lysine production with Corynebacterium glutamicum and systemic insight
      into citrate synthase flux and activity.
AB  - We here developed a series of Corynebacterium glutamicum strains with gradual
      decreased specific citrate synthase (CS) activity and quantified in a
      multifaceted approach the consequences of residual activity on the transcriptome,
      metabolome, and fluxome level as well as on L-lysine formation and growth. We
      achieved an intended gradual L-lysine yield increase and recognized and overcame
      further new limitations in the L-lysine biosynthesis pathway to result in a
      strain with the highest yield reported so far when assayed under comparable
      conditions. As a non-intended outcome, a detailed flux analysis revealed an
      almost constant flux through CS at 10% remaining CS activity, whereas the
      metabolome data revealed an increase in the oxaloacetate and acetyl-CoA
      concentrations. Hence reduced CS activity is apparently efficiently buffered by
      increased concentrations of CS substrates, implying a certain robustness of the
      central metabolism in response of the imposed gene expressions.

PMID- 22392074
TI  - IGFBP-rP1 induces p21 expression through a p53-independent pathway, leading to
      cellular senescence of MCF-7 breast cancer cells.
AB  - OBJECTIVES: Insulin-like growth factor-binding protein (IGFBP)-related protein 1
      (IGFBP-rP1), a member of the IGFBP super family, was identified as a potent tumor
      suppressor in several carcinomas. IGFBP-rP1 was down-regulated in primary breast
      cancer tissues and several breast cancer cell lines but overexpressed in
      senescent human mammary epithelial cells (HMECs), suggesting that IGFBP-rP1 might
      be a tumor suppressor in breast cancer and the tumor suppressor role of IGFBP-rP1
      might be associated with cellular senescence. The aim of the study was to observe
      the effect of IGFBP-rP1 on cellular senescence and the molecular events mediating
      this biological effect in MCF-7 breast cancer cells. METHODS: DNA fragment
      encoding IGFBP-rP1 was cloned in-frame N-terminally to EGFP gene to generate
      IGFBP-rP1-EGFP fusion protein expression plasmid (pEGFP-IGFBP-rP1). The plasmid
      pEGFP-IGFBP-rP1 was then transfected into MCF-7 cells, and the proliferation,
      cell cycle distribution, cellular senescence, and cell cycle-related protein
      expression of MCF-7 cells were examined by trypan blue exclusion, flow cytometry,
      senescence-associated galactosidase (SA-beta-gal) staining, and Western blot
      analysis, respectively. Two shRNA plasmid vectors against p21 or p53 gene were
      constructed and stably transfected into the MCF-7 cells to determine the
      involvement of p21 or p53 in cellular senescence induced by IGFBP-rP1. RESULTS:
      Transfection of IGFBP-rP1 or addition of condition medium (CM) from IGFBP-rP1
      transfected cells in MCF-7 cells caused induction of a variety of senescent
      phenotypes, such as decrease in cell proliferation, increase in G0/G1 cell cycle
      arrest cells, change in cell morphology, and increase in senescence-associated
      galactosidase (SA-beta-gal) activity. IGFBP-rP1-induced growth arrest is
      associated with enhanced expression of the cyclin-dependent kinase inhibitor p21
      and dephosphorylation of the retinoblastoma protein (pRB). Cell proliferation
      block and cellular senescence induction in response to IGFBP-rP1 were partially
      reversed by p21 knockdown in MCF-7 cells. Knockdown of p53 in MCF-7 cells did not
      influence the growth inhibition, cellular senescence, and p21 expression of the
      cells in response to IGFBP-rP1 transfection. CONCLUSIONS: Results from this study
      suggest that cellular senescence induced by IGFBP-rP1 is mediated at least in
      part by p21 enhanced expression, which regulated through the p53-independent
      pathway. IGFBP-rP1 might be one of the key molecules that trigger cellular
      senescence in breast cancer. Restoration of IGFBP-rP1 function might have
      therapeutic significance in breast cancer.

PMID- 22392075
TI  - Loco-recurrence after resection for ductal adenocarcinoma of the pancreas:
      predictors and implications for adjuvant chemoradiotherapy.
AB  - PURPOSE: Loco (regional)-recurrence rate after pancreaticoduodenectomy (PD) for
      pancreatic ductal adenocarcinoma (PDAC) remains high, and the efficiency of
      adjuvant chemoradiotherapy is still debated. We aimed to assess predictors of
      loco-recurrence in order to tailor the indications for adjuvant
      chemoradiotherapy. METHODS: Patients who underwent PD for PDAC between January
      2001 and December 2010 were retrieved from a prospective database. Tumor
      recurrence was categorized as either loco-recurrence or distant recurrence.
      Clinicopathological characteristics and survivals were compared between patients
      with different recurrence patterns. The predictors for loco-recurrence were
      assessed. RESULTS: Seventy-nine patients were included. Loco-recurrence alone was
      identified in 22 patients (27.8%), distant recurrence alone in 33 (41.8%), both
      loco- and distant recurrences in 17 (21.5%) and no recurrence in 7 (8.9%). Median
      survival after recurrence (SAR) was significantly better in patients with loco
      recurrence alone than in those with distant recurrence alone (10.4 vs. 5.0
      months, P = 0.002) or in those with both loco- and distant recurrences (10.4 vs.
      5.8 months, P = 0.044); the survival for patients with distant recurrence alone
      and those with both patterns was identical. Patients with early recurrence had a
      significantly poorer SAR than those with late recurrence (median, 5.5 vs. 9.0
      months, P = 0.001). Logistic regression analysis revealed that positive resection
      margin (P = 0.001, HR = 14.532; 95% CI 7.399-38.466), early T stage (P = 0.018,
      HR = 0.014; 95% CI 0.000-0.475) and large tumor size (P = 0.030, HR = 4.345; 95%
      CI 1.152-16.391) were the determinant factors directly related to loco-recurrence
      alone. CONCLUSIONS: Patients with PDAC loco-recurrence alone had a significantly
      better SAR than those with distant recurrence. Adjuvant chemoradiotherapy should
      be considered to reduce loco-recurrence further and improve long-term survival.

PMID- 22392076
TI  - The effects of cytokine-induced killer cells for the treatment of patients with
      solid tumors: a clinical retrospective study.
AB  - BACKGROUND: Cytokine-induced killer (CIK) cells exert high impact on adoptive
      immunotherapeutic approaches for malignant tumors. This study aimed to evaluate
      the effect of adjuvant immunotherapy with CIK cells on the prognosis of solid
      tumor. METHODS: Peripheral blood mononuclear cells were collected by a blood cell
      separator from 40 patients, then expanded by priming them with interferon-gamma
      followed by monoclonal antibody against CD3 and interleukin-2 the next day. The
      phenotypic patterns of CIK cells were characterized by flow cytometry on days 0,
      7, 10, 14 and 21 of incubation, respectively. Then, 5 ml of venous blood was
      obtained from 40 patients before and after CIK cells were transfused into
      patients to assess the influence of CIK cells on the percentages of effector
      cells. RESULTS: After 14 days of incubation in vitro, the percentages of CD3(+),
      CD8(+), CD3(+) and CD56(+) increased significantly (P < 0.05). The clinical
      symptoms of 40 patients were improved apparently. The 6-month, 1-year and 3-year
      overall survival rates were 70.0, 60.0 and 57.5%, respectively. CONCLUSIONS: Our
      results indicated that CIKs immunotherapy can be an effective adjuvant instrument
      of the routine therapy of malignancy.

PMID- 22392077
TI  - In vitro and in vivo anti-tumor activities of anti-EGFR single-chain variable
      fragment fused with recombinant gelonin toxin.
AB  - PURPOSE: Epidermal growth factor receptor (EGFR) plays an important role in the
      growth and metastasis of many solid tumors. Strategies that target EGFR hold
      promising therapeutic potential for the treatment for non-small cell lung cancer
      (NSCLC), as EGFR is normally overexpressed in these tumors. This study was
      designed to determine whether an anti-EGFR immunotoxin has anti-tumor activity
      against NSCLC, and if so, to further investigate the possible mechanisms of
      cytotoxicity. METHODS: A fusion protein of anti-EGFR single-chain variable
      fragment (anti-EGFR scFv) and the plant toxin gelonin (rGel) was constructed,
      expressed in bacteria, and purified to homogeneity. Cytotoxicity of anti-EGFR
      scFv/rGel (E/rG) immunotoxin was assessed on A549, HCC827, and H1975 cells (EGFR
      overexpressing NSCLC-derived cell lines) and A549 xenografts in nude mice.
      RESULTS: Cytotoxicity experiments using E/rG on A549, HCC827, and H1975 cells
      demonstrated that E/rG can specifically inhibit proliferation of these cells,
      whereas it did not affect the proliferation of Raji cells that do not express
      EGFR. Treatment for A549 xenografts in nude mice with E/rG resulted in
      significant suppression of tumor growth compared to controls. Immunofluorescence
      in frozen tissue sections confirmed that E/rG could specifically bind to tumor
      tissues in nude mice bearing A549 tumor xenografts, while rGel alone showed no
      binding activity. Furthermore, E/rG inhibited the growth of A549 cells by
      cytotoxic effects that blocked tumor proliferation, and the immunotoxin-induced
      cell death may be mediated by autophagy. CONCLUSIONS: These results showed that
      E/rG might have significant potential as a novel clinical therapeutic agent
      against human NSCLC.

PMID- 22392078
TI  - Greater intake of fruit and vegetables is associated with lower risk of
      nasopharyngeal carcinoma in Chinese adults: a case-control study.
AB  - PURPOSE: The effect of fruit and vegetable intake on the risk of nasopharyngeal
      carcinoma (NPC) remains uncertain due to limited published evidence. We performed
      a matched case-control study to investigate the relationship between the intake
      of fruit and vegetables and the risk of NPC. METHODS: Between July 2009 and March
      2011, 600 (448 male, 152 female), NPC incident cases from a single hospital in
      Guangzhou, Guangdong Province, China, a high-incidence area, were enrolled in the
      study. 600 controls, matched by gender, age (+/- 3 years) and household type
      (urban/rural) were also enrolled. Face-to-face interviews were used to collect
      habitual dietary intakes and information on various covariates. RESULTS:
      Multivariate conditional logistic regression analyses showed significant, dose
      dependent inverse associations between the intake of vegetables, fruit or a
      combination of the two and the risk of NPC, even after adjustments for social
      economic status, body mass index, dietary factors and other potential covariates.
      The adjusted odds ratios (95% confidence intervals) for NPC in the top quartile
      of vegetable intake, fruit intake or a combination of the two, as compared to the
      lowest quartile, were 0.33 (0.22-0.50), 0.70 (0.47-1.04) and 0.37 (0.25-0.55),
      respectively. Dark green leafy vegetables, carrots, peppers and tomatoes, citrus
      fruit and pome fruit showed much more pronounced benefits with regards to NPC
      than other types of fruit and vegetables. Interaction analyses demonstrated that
      the effects of total combined vegetable and fruit intake were much more
      significant in subjects with a higher education level (p interaction: 0.027), and
      the benefits of fruit were observed in males, but not in females (p interaction:
      0.088). CONCLUSION: Our findings suggest that a greater consumption of fruit and
      vegetables may lower the risk of NPC in Chinese adults.

PMID- 22392080
TI  - Questionable evidence of increasing incidence of invasive penile cancer in
      Denmark.

PMID- 22392079
TI  - Association of cord blood methylation fractions at imprinted insulin-like growth
      factor 2 (IGF2), plasma IGF2, and birth weight.
AB  - PURPOSE: Altered methylation at Insulin-like Growth Factor 2 (IGF2) regulatory
      regions has previously been associated with obesity, and several malignancies
      including colon, esophageal, and prostate adenocarcinomas, presumably via changes
      in expression and/or loss of imprinting, but the functional significance of these
      DNA methylation marks have not been demonstrated in humans. We examined
      associations among DNA methylation at IGF2 differentially methylated regions
      (DMRs), circulating IGF2 protein concentrations in umbilical cord blood (UCB) and
      birth weight in newborns. METHODS: Questionnaire data were obtained from 300
      pregnant women recruited between 2005 and 2009. UCB DNA methylation was measured
      by bisulfite pyrosequencing. UCB plasma concentrations of soluble IGF2 were
      measured by ELISA assays. Generalized linear regression models were used to
      examine the relationship between DMR methylation and IGF2 levels. RESULTS: Lower
      IGF2 DMR methylation was associated with elevated plasma IGF2 protein
      concentrations (beta = -9.87, p < 0.01); an association that was stronger in
      infants born to obese women (pre-pregnancy BMI > 30 kg/m(2), beta = -20.21, p <
      0.0001). Elevated IGF2 concentrations were associated with higher birth weight (p
      < 0.0001) after adjusting for maternal race/ethnicity, pre-pregnancy BMI,
      cigarette smoking, gestational diabetes, and infant sex. These patterns of
      association were not apparent at the H19 DMR. CONCLUSION: Our data suggest that
      variation in IGF2 DMR methylation is an important mechanism by which circulating
      IGF2 concentrations, a putative risk factor for obesity and cancers of the colon,
      esophagus, and prostate, are modulated; associations that may depend on pre
      pregnancy obesity.

PMID- 22392081
TI  - Paclitaxel enhances therapeutic efficacy of the F8-IL2 immunocytokine to EDA
      fibronectin-positive metastatic human melanoma xenografts.
AB  - The selective delivery of bioactive agents to tumors reduces toxicity and
      enhances the efficacy of anticancer therapies. In this study, we show that the
      antibody F8, which recognizes perivascular and stromal EDA-fibronectin (EDA-Fn),
      when conjugated to interleukin-2 (F8-IL2) can effectively inhibit the growth of
      EDA-Fn-expressing melanomas in combination with paclitaxel. We obtained curative
      effects with paclitaxel administered before the immunocytokine. Coadministration
      of paclitaxel increased the uptake of F8 in xenografted melanomas, enhancing
      tumor perfusion and permeability. Paclitaxel also boosted the recruitment of F8
      IL2-induced natural killer (NK) cells to the tumor, suggesting a host response as
      part of the observed therapeutic benefit. In support of this likelihood, NK cell
      depletion impaired the antitumor effect of paclitaxel plus F8-IL2. Importantly,
      this combination reduced both the tumor burden and the number of pulmonary
      metastatic nodules. The combination did not cause cumulative toxicity. Together,
      our findings offer a preclinical proof that by acting on the tumor stroma
      paclitaxel potentiates the antitumor activity elicited by a targeted delivery of
      IL2, thereby supporting the use of immunochemotherapy in the treatment of
      metastatic melanoma.

PMID- 22392082
TI  - [Updating of the Brazilian guideline for chronic heart failure - 2012].

PMID- 22392083
TI  - Defensive secretions of the carabid beetle Chlaenius cordicollis: chemical
      components and their geographic patterns of variation.
AB  - The defensive secretion of the ground beetle Chlaenius cordicollis is
      predominantly 3-methylphenol. Adult C. cordicollis were collected in Pennsylvania
      and Manitoba and induced to discharge defensive secretion in a vial. The
      headspace was sampled by solid phase microextraction, and samples were analyzed
      by gas chromatography-mass spectrometry. Five alkylphenolic compounds were
      detected: all beetles secreted 3-methlyphenol, 2,5-dimethylphenol, and 3
      ethylphenol, and most beetles from each locality secreted detectable amounts of
      2,3-dimethlyphenol and 3,4-dimethylphenol. In about 80% of beetles, we detected
      small amounts of the alkoxyphenolic compounds 2-methoxy-4-methylphenol and 2
      methoxy-5-methylphenol. Multivariate compositional analysis of relative peak
      areas of alkylphenolic compounds revealed geographic variation and sexual
      dimorphism in defensive secretions. Compared with samples from Manitoba, relative
      peak areas of samples from Pennsylvania were lower for 2,3-dimethylphenol and
      higher for 3-methylphenol. Sexual dimorphism was detected only in Manitoba where,
      compared with samples from males, relative peak areas for samples from females
      were higher for 2,5-dimethylphenol and lower for 3-ethylphenol. This is the first
      report of geographic variation in defensive secretions of carabid beetles, and it
      demonstrates the need for knowledge of patterns of variation before
      characterizing the defensive secretions of a species as a whole.

PMID- 22392084
TI  - In the nick of time: males of the parasitoid wasp Pimpla disparis respond to
      semiochemicals from emerging mates.
AB  - Males of the parasitoid wasp Pimpla disparis Viereck (Hymenoptera: Ichneumonidae)
      aggregate on parasitized gypsy moth, Lymantria dispar, host pupae when the
      emergence of a prospective mate is imminent or under way. We tested the
      hypotheses that the developing parasitoid ("DePa") inside the host pupal case
      produces a pheromone that attracts and arrests mate-seeking males, and that the
      pheromone is most effective during the emergence of the parasitoid from the host.
      Results obtained in two-choice laboratory experiments, with 4-7-d-old virgin
      males, indicate that (1) DePa-derived semiochemicals arrest males, (2) the
      opening of a host pupal case strongly arrests males, and (3) the arrestment cue
      emanates from oral fluid secreted by both female and male parasitoids while they
      chew their way out of a host pupal case. This phenomenon implies that emerging
      females, which are haplodiploid and can reproduce without mating, do not engage
      in active pheromone signaling to attract males, and that mate-seeking males co
      opt chemicals involved in eclosion as a mate-finding cue, taking a 50% chance
      that the prospective mate is a female.

PMID- 22392085
TI  - Nocturnal bees are attracted by widespread floral scents.
AB  - Flower localization in darkness is a challenging task for nocturnal pollinators.
      Floral scents often play a crucial role in guiding them towards their hosts.
      Using common volatile compounds of floral scents, we trapped female nocturnal
      Megalopta-bees (Halictidae), thus uncovering olfactory cues involved in their
      search for floral resources. Applying a new sampling method hereby described, we
      offer novel perspectives on the investigation of nocturnal bees.

PMID- 22392086
TI  - Poorly Differentiated Neuroendocrine Carcinoma of the Sigmoid Colon-a Rare
      Differential Diagnosis of Malignant Colon Tumours.

PMID- 22392087
TI  - Primary CD138-Positive Poorly Cohesive Adenocarcinoma of the Stomach Whose
      Carcinoma Cells Resemble Plasma Cells (Plasmacytoid Adenocarcinoma of the
      Stomach).

PMID- 22392088
TI  - After distal pancreatectomy pancreatic leakage from the stump of the pancreas may
      be due to drain failure or pancreatic ductal back pressure.
AB  - HYPOTHESIS: The method to lower postoperative pancreatic fistula (POPF) after
      distal pancreatectomy (DP) involves controlling risk factors for leakage from the
      pancreatic stump. GOAL: The aim of this study was to identify controllable risk
      factors for POPF. METHODS: In order to promote homogeneity, we used a single
      surgeon case series and then calculated POPF with a public web-based tool based
      on the severity classification system of the International Study Group of
      Pancreatic Surgery (ISGPS). A total of 223 consecutive cases of DPs were
      reviewed. DP involved the same hand-sewn fish-mouth closure of the pancreatic
      stump. All received postoperative epidural anesthesia. Logistic regression
      analysis identified risk factors for clinically relevant POPF (grade B/C).
      RESULTS: Mortality was zero. ISGPS gradings were: no POPF 53%, grade A = 32%, B =
      13.9%, and C = 0.9%. The clinical-relevant POPF (B/C) rate was 14.8% of which 24%
      represented surgical drain failure due to lack of patency and/or misplaced from
      their original location. Preoperative endoscopic ablation and/or stenting of
      Wirsung's duct was a significant risk factor to lower grade B/C leak (3%).
      Multivariate analysis identified two controllable risk factors-intraoperative
      blood loss >1,000 ml and those who did not undergo preoperative endoscopic
      interventions of Wirsung's duct. In the group with presumed intact pancreatic
      sphincters (no endoscopic intervention, n = 177), the use of postoperative
      intravenous opioids (with epidural failure) was a risk factor for B/C leak (34%).
      These findings suggest that increased back pressure in the pancreatic duct has a
      role in promoting pancreatic stump leakage. CONCLUSIONS: Using the ISGPS
      definition and its web-based tool, the incidence of clinically relevant leakage
      was 14.8% in 223 cases of DP. Opportunities to lower this rate are improving our
      surgical drain technology, limiting intraoperative blood loss, and avoiding
      postoperative intravenous narcotics with epidural analgesia.

PMID- 22392089
TI  - Usefulness of pyloric reconstruction without compromising curative resection in
      gastric cancer treatment.
AB  - INTRODUCTION: We herein report the short-term results of the newly developed
      modified technique of Billroth I (modified B-I; pylorus reconstruction) that
      prevents duodenogastric reflux (DGR) and remnant gastritis after distal
      gastrectomy. PATIENTS AND METHODS: Distal gastrectomy with this technique was
      performed in 20 patients (age, 41 to 86 years [mean, 68.5 +/- 11.8 years],
      male/female = 12:8) with gastric cancer from June 2006 through December 2009.
      These patients were compared with another 20 patients who underwent conventional
      B-I after distal gastrectomy (age, 41 to 85 years [mean, 69.3 +/- 8.69 years],
      male/female = 11:9). The side effects of gastric surgery evaluated in this study
      were the degree of remnant gastritis, the presence of dumping syndrome, and the
      degree of weight loss. RESULTS: By gastrografin contrast imaging on the fifth day
      after pylorus reconstruction, the remnant stomach was not dilated and
      gastrografin flowed physiologically to the duodenum without backward reflux into
      the remnant stomach. By gastroscopy at 6 months after the operation, DGR and the
      degree of remnant gastritis after pylorus reconstruction was lower than those of
      conventional B-I (P = 0.00068). The bile acid concentration of remnant gastric
      juice of pylorus reconstruction was lower than that of conventional B-I (55.5 +/-
      93.5 vs. 1,369.5 +/- 2,502.1 MUmol/L, P = 0.0415). Weight loss at 1 year after
      distal gastrectomy was less in pylorus reconstruction compared with conventional
      B-I (6.2 +/- 5.2% vs. 9.8 +/- 8.7%, P = 0.0725). CONCLUSION: Pylorus
      reconstruction is a simple and safe anastomotic technique that reduces the side
      effects of B-I reconstruction.

PMID- 22392091
TI  - Small-gauge vitrectomy does not protect against nuclear sclerotic cataract.
AB  - PURPOSE: To determine whether the gauge of vitrectomy instrumentation is
      associated with the progression of nuclear sclerotic cataract. METHODS: A
      prospective interventional and observational study of patients undergoing
      vitrectomy surgery for various retinal conditions. Patients had Scheimpflug lens
      photography in the operated and fellow eye at baseline and at 6 months and 12
      months after vitrectomy surgery. RESULTS: Of 42 eyes included in the analysis, 11
      had 20-gauge surgery, 22 had 23-gauge surgery, and 9 had 25-gauge surgery. In all
      operated eyes, vitrectomy surgery led to the significant progression of nuclear
      sclerotic cataract, compared with the fellow, unoperated eye. This small study
      was unable to detect a difference in nuclear sclerotic progression when comparing
      small-gauge surgery (23 and 25 gauge) with standard 20-gauge surgery. CONCLUSION:
      Removal of the vitreous gel using any-gauge vitrectomy surgery leads to
      significant progression of nuclear sclerotic cataract at 6 months and 12 months.
      The findings are consistent with the hypothesis that the vitreous gel is
      important in protecting the lens from increased exposure to oxygen that leads to
      the formation of nuclear sclerotic cataract. This increased exposure to oxygen
      occurs as a result of removing the vitreous gel and is independent of the gauge
      of vitrectomy instrumentation.

PMID- 22392090
TI  - Surgical management of pancreaticobiliary disease associated with juxtapapillary
      duodenal diverticula: case series and review of the literature.
AB  - INTRODUCTION: Juxtapapillary duodenal diverticula (DD), although usually
      asymptomatic, are occasionally associated with pancreaticobiliary conditions such
      as recurrent bile duct stones, cholangitis, and pancreatitis. MATERIALS AND
      METHODS: An unusual case of DD associated with a dorsal duct stricture in a
      patient with recurrent pancreatitis and pancreas divisum is presented along with
      three additional instances of surgically treated DD and a review of the
      literature. RESULTS: The role of surgical intervention depends upon the specific
      nature of the presentation and the anatomical relationship of the diverticulum to
      the ampullary and pancreaticobiliary ductal system. CONCLUSION: Operations that
      divert bile and the food stream from DD are preferred over diverticulectomy.

PMID- 22392092
TI  - Anatomical and visual outcomes of macular hole surgery with short-duration 3-day
      face-down positioning.
AB  - PURPOSE: The role of face-down posturing after macular hole (MH) surgery remains
      unclear and controversial. We evaluated the anatomical and visual outcomes of MH
      repair using a short duration (3 days) of prone positioning. METHODS: Prospective
      series of 50 consecutive eyes in 50 patients with Stage 2 or Stage 3 idiopathic
      MHs. All eyes underwent vitrectomy MH surgery with internal limiting membrane
      peeling and 20% sulfur hexafluoride (SF6) gas tamponade. The procedure was
      combined with phacoemulsification cataract surgery in phakic eyes. Surgical
      outcomes, MH closure rates, complications, and postoperative visual acuity were
      investigated. RESULTS: Anatomical closure of MHs was achieved in 49 (98%) of 50
      eyes by 1 surgery. Postoperative logarithm of the minimum angle of resolution
      visual acuity decreased (i.e., improved) by 0.271 (95% confidence interval, 0.101
      0.441 [P = 0.0024]). One complication of intraocular lens pupillary capture and
      one case of chronic cystoid macular edema were observed. There were no
      complications attributed to intraocular pressure fluctuations. CONCLUSION:
      Vitrectomy with internal limiting membrane peeling and gas tamponade with SF6
      followed by short-duration 3-day face-down positioning is a successful surgical
      intervention for Stage 2 and Stage 3 idiopathic MHs. This method possessed
      minimal complications and offered significant improvement in visual acuity.

PMID- 22392093
TI  - Effect of Brilliant Blue G on the retinal ganglion cells of rats.
AB  - PURPOSE: To investigate the effects of Brilliant Blue G (BBG) on rat retinal
      ganglion cells (RGCs), both in vitro and in vivo. METHODS: In vitro, rat RGCs
      were purified by a 2-step immunopanning procedure, briefly exposed to BBG (250
      mg/L), and irradiated with an endoilluminator for 15 minutes or incubated in the
      presence of BBG (concentration, 2-250 mg/L) without irradiation. The number of
      viable RGCs was counted after 3 days in culture. In vivo, after rats received an
      intravitreal injection of 3 MUL of BBG (0.25 and 2.5 mg/L), the number of viable
      RGCs was examined by a 1,1'-dioctadecyl-1-3,3,3',3'-tetramethylindocarbocyanine
      perchlorate-retrolabeling technique. RESULTS: In vitro, a brief exposure to BBG
      and irradiation did not affect RGC survival. However, BBG reduced the number of
      viable RGCs in a dose-dependent manner when the cells were exposed for 3 days. In
      vivo, when rats received an intravitreous injection of 0.25 mg/L BBG, the number
      of viable RGCs was not affected. The number of viable RGCs showed a tendency to
      decrease in the 2.5-mg/L group 14 days after the injection, but the difference
      was not significant compared with the number in the saline-treated control group.
      CONCLUSION: Brilliant Blue G exerts no detectable detrimental effect on RGCs
      after short-time exposure, and no significant toxic effect even after a longer
      time exposure in the current experimental setting.

PMID- 22392095
TI  - Phosphaalkenyl germylenes and their gold, tungsten and molybdenum complexes.
AB  - The new bis(phosphaalkenyl) germanium(II) compound (NHC)Ge(CCl=PMes*)(2) reacts
      with L(2)M(CO)(4) (M = Mo, W) to give bidentate complexes with an unexpected
      coordinating behaviour involving the Ge(II) centre and one phosphorus atom, and
      with AuI or Me(2)SAuCl to afford the monodentate complexes coordinated at the
      germanium(II) atom.

PMID- 22392094
TI  - Over-expression of BMP4 inhibits experimental choroidal neovascularization by
      modulating VEGF and MMP-9.
AB  - Bone morphorgenetic protein (BMP)-4 has been shown to play a pivotal role in eye
      development; however, its role in mature retina or ocular angiogenic diseases is
      unclear. Activating downstream Smad signaling, BMP4 can be either pro-angiogenic
      or anti-angiogenic, depending on the context of cell types and associated
      microenvironment. In this study, we generated transgenic mice over-expressing
      BMP4 in retinal pigment epithelial (RPE) cells (Vmd2-Bmp4 Tg mice), and used the
      laser-induced choroidal neovascularization (CNV) model to study the angiogenic
      properties of BMP4 in adult eyes. Vmd2-Bmp4 Tg mice displayed normal retinal
      histology at 10 weeks of age when compared with age-matched wildtype mice. Over
      expression of BMP4 in RPE in the transgenic mice was confirmed by real-time PCR
      and immunostaining. Elevated levels of Smad1,5 phosphorylation were found in BMP4
      transgenic mice compared to wildype mice. Over-expression of BMP4 was associated
      with less severe CNV as characterized by fluorescein angiography, CNV volume
      measurement and histology. While control mice showed increased levels of vascular
      endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 after laser
      injury, Vmd2-Bmp4 Tg showed no increase in either VEGF or MMP-9. Further, we
      found that TNF-induced MMP-9 secretion in vitro was reduced by pretreatment of
      RPE cells with BMP4. The inhibition of MMP-9 was Smad-dependent because BMP4
      failed to repress TNF-induced MMP-9 expression when Smad1,5 was silenced by
      siRNA. In summary, our studies identified an anti-angiogenic role for BMP4 in
      laser-induced CNV, mediated by direct inhibition of MMP-9 and indirect inhibition
      of VEGF.

PMID- 22392096
TI  - Lung cancer: Maintenance chemotherapy--a stitch in time saves nine?

PMID- 22392097
TI  - Exercise rehabilitation in patients with cancer.
AB  - Emerging evidence indicates that patients with cancer have considerable
      impairments in cardiorespiratory fitness, which is likely to be a result of the
      direct toxic effects of anticancer therapy as well as the indirect consequences
      secondary to therapy (for example, deconditioning). This reduced
      cardiorespiratory fitness is associated with heightened symptoms, functional
      dependence, and possibly with an increased risk of cardiovascular morbidity and
      mortality. Current understanding of the complex interaction between the effects
      of the tumour and cancer-associated therapies on the organ components that govern
      cardiorespiratory fitness, and the effects of exercise training on these
      parameters is limited; further research will be critical for further progress of
      exercise-based rehabilitation in the oncology setting. We assess the current
      evidence regarding the level, mechanisms, and clinical importance of diminished
      cardiorespiratory fitness in patients with cancer. The efficacy and adaptations
      to exercise training to prevent and/or mitigate dysfunction in conjunction with
      exercise prescription considerations for clinical use are also discussed.

PMID- 22392098
TI  - In silico analysis of drug-resistant mutant of neuraminidase (N294S) against
      oseltamivir.
AB  - The recent H1N1 influenza pandemic has attracted worldwide attention due to the
      high infection rate. Oseltamivir is a new class of anti-viral agent approved for
      the treatment and prevention of influenza infections. The principal target for
      this drug is a virus surface glycoprotein, neuraminidase (NA), which facilitates
      the release of nascent virus and thus spreads infection. Until recently, only a
      low prevalence of neuraminidase inhibitor (NAI) resistance (<1 %) had been
      detected in circulating viruses. However, there have been reports of significant
      numbers of A (H1N1) influenza strains with a N294S neuraminidase mutation that
      was highly resistant to the NAI, oseltamivir. Hence, in the present study, we
      highlight the effect of point mutation-induced oseltamivir resistance in H1N1
      subtype neuraminidases by molecular simulation approach. The docking analysis
      reveals that mutation (N294S) significantly affects the binding affinity of
      oseltamivir with mutant type NA. This is mainly due to the decrease in the
      flexibility of binding site residues and the difference in prevalence of hydrogen
      bonds in the wild and mutant structures. This study throws light on the possible
      effects of drug-resistant mutations on the large functionally important
      collective motions in biological systems.

PMID- 22392099
TI  - Ovarian cancer and the pelvic floor surgeon: the case for prophylactic bilateral
      salpingectomy during POP surgery.

PMID- 22392100
TI  - Can simple codon pair usage predict protein-protein interaction?
AB  - Deciphering functional interactions between proteins is one of the great
      challenges in biology. Sequence-based homology-free encoding schemes have been
      increasingly applied to develop promising protein-protein interaction (PPI)
      predictors by means of statistical or machine learning methods. Here we analyze
      the relationship between codon pair usage and PPIs in yeast. We show that codon
      pair usage of interacting protein pairs differs significantly from randomly
      expected. This motivates the development of a novel approach for predicting PPIs,
      with codon pair frequency difference as input to a Support Vector Machine
      predictor, termed as CCPPI. 10-fold cross-validation tests based on yeast PPI
      datasets with balanced positive-to-negative ratios indicate that CCPPI performs
      better than other sequence-based encoding schemes. Moreover, it ranks the best
      when tested on an unbalanced large-scale dataset. Although CCPPI is subjected to
      high false positive rates like many PPI predictors, statistical analyses of the
      predicted true positives confirm that the success of CCPPI is partly ascribed to
      its capability to capture proteomic co-expression and functional similarities
      between interacting protein pairs. Our findings suggest that codon pairs of
      interacting protein pairs evolve in a coordinated manner and consequently they
      provide additional information beyond amino acids-based encoding schemes. CCPPI
      has been made freely available at: http://protein.cau.edu.cn/ccppi.

PMID- 22392101
TI  - Incontinence after colonoscopy--an unrecognized and preventable problem. A cross
      sectional study from the Gastronet quality assurance program.
AB  - BACKGROUND: Colonoscopy requires insufflation of gas for visualization of the
      bowel wall. Worldwide, this is usually done using air. The aim of the present
      study was to assess the risk of postcolonoscopy incontinence, and to investigate
      whether insufflation of CO2 instead of air may reduce this risk, since it is
      easily absorbed through the bowel mucosa. METHODS: This is a prospective
      multicenter study of colonoscopy patients undergoing bowel insufflation using air
      or CO2. A successive series of colonoscopies were reported to a national quality
      assurance program in Norway between January and December 2009 from 21 endoscopy
      centers with varying insufflation practices. The study comprised 7812 patients
      aged 18 years or older who were referred for outpatient colonoscopy. Of these,
      5015 underwent colonoscopy performed using air and 2797 colonoscopy using CO2
      insufflation. RESULTS: Patient-reported incontinence up to 24 h after colonoscopy
      was compared using binary logistic regression analysis for the type of gas used
      for insufflation. The air and CO2 patient groups were comparable with regard to
      age, sex, indication for colonoscopy, and sedation practice. Incontinence was
      reported by 336 out of 7812 patients (4.3%). Incontinence was significantly less
      frequent in the CO2 group than in the air group [2.1% versus 5.5%; adjusted odds
      ratio (OR) 0.38; 95%CI 0.28-0.50; P < 0.001]. Female patients had a higher risk
      of incontinence than men (adjusted OR 1.77; 95% CI 1.39-2.24; P < 0.001).
      CONCLUSION: About every 20th patient undergoing colonoscopy using standard air
      insufflation experiences postexamination incontinence. This proportion can be
      reduced by 60% by converting from air insufflation to insufflation with the
      absorbable CO2.

PMID- 22392102
TI  - Lanthanide-mediated triangular cationic assemblies: structural and physico
      chemical properties.
AB  - This contribution investigates Ln(III) complexes formed with a small ditopic
      ligand, L1, and their structural, thermodynamic and photophysical properties. The
      spectrophotometric and NMR titrations evidence the triangular assemblies
      [Ln(3)(L1-H)(3)](6+) at stoichiometric conditions and their properties are
      discussed in relation to L2-containing analogues. In addition, the dinuclear
      species, [Ln(2)(L1-H)](5+), is observed with an excess of metal.

PMID- 22392103
TI  - Uric acid is an important predictor for hypertensive early atherosclerosis.
AB  - INTRODUCTION: The association between hyperuricemia and cardiovascular disease in
      hypertensive subjects is controversial. Attempts to elucidate the possible
      association between hyperuricemia and early atherosclerosis in hypertensive
      patients may provide alternative prevention or therapy targets for future
      cardiovascular events. METHODS: A total of 67 hypertensive and 30 healthy
      subjects underwent B-mode ultrasonography to measure carotid intima media
      thickness (C-IMT). All biochemical analyses were assessed by local laboratories
      using standard laboratory methods. RESULTS: C-IMT, serum uric acid (UA) levels,
      and mean arterial blood pressure (MBP) levels were significantly higher in
      hypertensive population compared to healthy subjects (P<0.001). Among
      hypertensive subjects, high sensitivity C-reactive protein (hs-CRP), C-IMT, and
      proteinuria levels were significantly higher in hyperuricemic patients compared
      to normouricemic participants (for all, P<0.05). Age (r=0.28, P=0.02), MBP
      (r=0.34, P=0.04), hs-CRP (r=0.58, P=0.006), proteinuria (r=0.58, P=0.007),
      estimated glomerular filtration rate (r=-0.35, P=0.02), and UA (r=0.31, P=0.02)
      levels were significantly associated with C-IMT levels. Multiple linear
      regression analysis using C-IMT as a dependent variable showed that age
      (beta=0.84, P=0.03) and UA levels (beta=-0.87, P=0.02) were independently
      associated with C-IMT. CONCLUSION: Hyperuricemia is an independent predictor for
      early atherosclerosis in hypertensive subjects with normal renal function.
      Therefore, the optimal control of UA may provide further benefits in preventing
      atherosclerosis and hypertensive end-organ injury.

PMID- 22392104
TI  - MRI classification of asymmetric septal hypertrophic cardiomyopathy and its
      relation to the presence of risk factors.
AB  - Asymmetric septal hypertrophic cardiomyopathy (ASH) is the common phenotype of
      hypertrophic cardiomyopathy (HCM). We sought to classify ASH using magnetic
      resonance imaging (MRI) and to determine whether the MRI classification of ASH is
      related to the presence of risk factors for HCM. Ninety-three patients with ASH
      underwent cine and delayed-enhancement MRI. The ASH was classified
      morphologically using cine MRI at end-diastole. We evaluated the association
      between the MRI findings and the presence of risk factors in the ASH. The ASH was
      classified into three subtypes by MRI: contiguous subtype showing various
      clinical and MRI features (57%), sigmoid subtype (29%) with fewer risk factors,
      and reverse-curve subtype (14%) in younger patients with the larger myocardial
      mass and delayed-enhancement, which were significantly related to the risk
      factors. MRI was used to classify ASH into three subtypes, which might be related
      to the presence of risk factors.

PMID- 22392105
TI  - Comparison of cardiac MRI tissue tracking and myocardial tagging for assessment
      of regional ventricular strain.
AB  - This study sought to compare regional measures of ventricular strain by tissue
      tracking (TT) to those derived from myocardial tagging (MT) within cardiac MR
      (CMR), in normal subjects and patients with hypertrophic cardiomyopathy. CMR
      images from 13 normal subjects and 11 subjects with hypertrophic cardiomyopathy
      were retrospectively analyzed. For each subject, equivalent mid-papillary level
      short-axis cine steady-state free precession and MT slices from the same
      examination were evaluated. The time to peak circumferential strain and magnitude
      of the peak strain were calculated for 6 matched left ventricular segments. Data
      from 24 slices (n = 144 segments) were compared. The mean difference between
      techniques in magnitude of peak strain and time to peak strain was 1 +/- 9% and 1
      +/- 58 ms, respectively. The mean difference in the standard deviation of time to
      peak strain within a slice was 0 +/- 19 ms (mean cardiac cycle duration 1,013 +/-
      204 ms). Bland-Altman analysis showed closer agreement in time to peak strain
      than peak strain magnitude. Measurements of segmental time to peak strain by TT
      and MT were in close agreement; agreement for the magnitude of peak segmental
      strain was more modest. The TT approach does not add to CMR examination time and
      may be a useful tool for the assessment of ventricular synchrony.

PMID- 22392106
TI  - Lessons from the epidemiology of neuropsychiatric disorders in older people.

PMID- 22392107
TI  - The role of magnetic resonance imaging in the management of schistosomal
      myeloradiculopathy.

PMID- 22392108
TI  - Use of psychotropic medications by caregivers of elderly patients with dementia:
      is this a sign of caregiver burden?
AB  - This study evaluated the consumption of psychotropic medications by caregivers of
      elderly patients with or without dementia. This was a cross-sectional study
      conducted at all geriatric units in Brasilia, Brazil, during a two-month period.
      Structured interviews were performed with 311 caregivers of people with or
      without dementia and they completed questionnaires. Among the caregivers, 196
      (63%) were caregivers of patients with dementia and 115 (37%) were caregivers of
      patients without dementia. Forty-four caregivers (14.1%) were taking psychotropic
      drugs (benzodiazepines or antidepressants), and this usage was more frequent
      among caregivers of patients with dementia (p<0.01). Twenty-two caregivers of
      patients with dementia (11.4%) had used sleeping pills after beginning care,
      compared with only five (4.3%) caregivers of patients without dementia (p<0.01).
      In conclusion, this study found that caregivers of patients with dementia took
      psychotropic drugs (benzodiazepines and antidepressants) more frequently than the
      ones of patients without dementia.

PMID- 22392109
TI  - Low quality of life scores in school children with attention deficit
      hyperactivity disorder related to anxiety.
AB  - OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is an alteration that
      begins early in infancy and whose cardinal symptoms are inattention,
      hyperactivity and impulsivity. There are few studies for specific tests to
      measure Quality of Life (QoL) in children with ADHD. METHODS: We evaluated QoL of
      120 children from 7-12 years of age with ADHD and of a group of 98 healthy
      control children. To measure QoL, we utilized the Questionnaire of Quality of
      Life for Children in Pictures (AutoQuestionnaire Qualite de Vie Enfant Image,
      AUQUEI). We evaluated anxiety in children by the Children's Manifest Anxiety
      Scale-Revisited (CMAS-R). We compared results among groups and employed the
      calculation of correlation between the AUQUEI questionnaire and the CMAS-R scale.
      RESULTS: The total average of the AUQUEI questionnaire in children with ADHD was
      45.2, while in the control group it was 54.3 (p<0.05). We also observed
      significant differences between the control group and groups of children with
      ADHD in the CMAS-R scale. We found significant correlations between AUQUEI
      questionnaire and CMAS-R scale. CONCLUSION: The main result was to the disclosure
      that low QoL scores in ADHD children was anxiety-related.

PMID- 22392110
TI  - Translation and validation of Autism Diagnostic Interview-Revised (ADI-R) for
      autism diagnosis in Brazil.
AB  - OBJECTIVE: To translate into Brazilian Portuguese the Autism Diagnostic Interview
      Revised (ADI-R), an extremely useful diagnostic tool in autism. METHODS: A case
      control study was done to validate the ADI-R. After being translated, the
      interview was applied in a sample of 20 patients with autism and 20 patients with
      intellectual disability without autism, in order to obtain the initial
      psychometric properties. RESULTS: The internal consistency was high, with a of
      Crombach of 0.967. The validity of criterion had sensitivity and specificity of
      100%, having as a gold standard the DSM-IV diagnostic criteria. The interview had
      high discriminant validity, with higher scores in the group of patients with
      autism, as well as high interobserver consistency, with median kappa of 0.824.
      CONCLUSION: The final version of ADI-R had satisfactory psychometric
      characteristics, indicating good preliminary validation properties. The
      instrument needs to be applied in bigger samples in other areas of the country.

PMID- 22392111
TI  - Motor function measure scale, steroid therapy and patients with Duchenne muscular
      dystrophy.
AB  - OBJECTIVE: To assess the evolution of motor function in patients with Duchenne
      muscular dystrophy (DMD) treated with steroids (prednisolone or deflazacort)
      through the Motor Function Measure (MFM), which evaluates three dimensions of
      motor performance (D1, D2, D3). METHODS: Thirty-three patients with DMD (22
      ambulant, 6 non-ambulant and 5 who lost the capacity to walk during the period of
      the study) were assessed using the MFM scale six times over a period of 18
      months. RESULTS: All the motor functions remained stable for 14 months in all
      patients, except D1 for those who lost their walking ability. In ambulant
      patients, D2 (axial and proximal motor capacities) motor functions improved
      during six months; an improvement in D3 (distal motor capacity) was noted during
      the total follow-up. D1 (standing posture and transfers) and total score were
      useful to predict the loss of the ability to walk. CONCLUSIONS: The use of the
      MFM in DMD patients confirms the benefits of the steroid treatment for slowing
      the progression of the disease.

PMID- 22392112
TI  - Motor Activity Log-Brazil: reliability and relationships with motor impairments
      in individuals with chronic stroke.
AB  - The Motor Activity Log (MAL) assesses the spontaneous use of the most affected
      upper limb with the amount of use (AOU) and quality of movement (QOM) scales
      during daily activities in real environments in individuals with chronic stroke.
      OBJECTIVES: This study translated the testing manual into Portuguese and assessed
      the inter-rater and test-retest reliabilities of the MAL, based upon the
      Brazilian manual version. METHODS: The inter-rater reliability was evaluated by
      comparing the results of two examiners, and the test-retest reliability was
      tested by comparing the results of two evaluations, repeated one-week apart with
      30 individuals with chronic hemiparesis (55.8+/-15.1 years). RESULTS: The intra
      class correlation coefficients (ICCs) for the total scores were adequate for both
      the inter-rater (0.98 for the AOU and 0.91 for QOM) and test-retest reliabilities
      (0.99 for both scales). CONCLUSIONS: The results suggested that the MAL was
      reliable to evaluate the spontaneous use of the most affected upper limb after
      stroke.

PMID- 22392113
TI  - Serum C-reactive protein levels predict neurological outcome after aneurysmal
      subarachnoid hemorrhage.
AB  - OBJECTIVES: Our aim was to evaluate the relationship between serum C-reactive
      protein (CRP) levels and the neurological prognosis and development of vasospasm
      in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Eighty-two
      adult patients with aSAH diagnoses were prospectively evaluated. Glasgow Coma
      Scale (GCS) score, Hunt and Hess grade, Fisher grade, cranial CT scans, digital
      subtraction angiography studies and daily neurological examinations were
      recorded. Serial serum CRP measurements were obtained daily between admission and
      the tenth day. Glasgow Outcome Scale (GOS) and the modified Rankin Scale (mRS)
      were used to assess the prognosis. RESULTS: Serum CRP levels were related to
      severity of aSAH. Patients with lower GCS scores and higher Hunt and Hess and
      Fisher grades presented statistically significant higher serum CRP levels.
      Patients with higher serum CRP levels had a less favorable prognosis.
      CONCLUSIONS: Increased serum CRP levels were strongly associated with worse
      clinical prognosis in this study.

PMID- 22392114
TI  - Scar neuromas as triggers for headache after craniotomy: clinical evidence.
AB  - We present four cases of headache with variable intensity, located in close
      proximity to a craniotomy incision which was performed for non-traumatic reasons.
      Since manual palpation of the scar often triggers pain, and infiltration with
      local anesthetics reduce or abolish the pain in some patients, we suggest that
      neuromas or nerve entrapment in the scars, as a result of the surgery, are
      responsible for headaches. Although local infiltrations or nerve blocks are often
      used for diagnostic reasons, herein we consider that they are also of therapeutic
      value. We review the current known pathophysiology of post-craniotomy headaches
      and present a hypothesis suggesting a greater recognition of the potential
      contribution of neuroma formation in areas of scars tissue to contribute to this
      kind of headache.

PMID- 22392115
TI  - Extensive spinal cord involvement in magnetic resonance imaging evaluation on
      schistosomal myelitis.
AB  - The diagnosis of schistosomal myelitis (SM) is frequently presumptive because no
      findings from any complementary examination are pathognomonic for this disease.
      The present report describes some abnormalities seen on magnetic resonance
      imaging (MRI) evaluation of a series of SM patients and discusses their
      etiopathogenesis. METHODS: This study evaluated SM patients at the time of their
      diagnosis. These patients routinely underwent MRI on all segments of the spinal
      cord. RESULTS: Thirteen patients were evaluated. The MRI was abnormal in 12
      (92.3%) of them. In 11 patients (84.61%), the damage reached two or more spinal
      segments. CONCLUSIONS: MRI was an important diagnostic aid in this sample,
      because of the high rate of abnormalities detected. The tissue damage observed on
      MRI was extensive in the majority of the patients.

PMID- 22392116
TI  - Aquaporin 9 in rat brain after severe traumatic brain injury.
AB  - OBJECTIVE: To reveal the expression and possible roles of aquaporin 9 (AQP9) in
      rat brain, after severe traumatic brain injury (TBI). METHODS: Brain water
      content (BWC), tetrazolium chloride staining, Evans blue staining,
      immunohistochemistry (IHC), immunofluorescence (IF), western blot, and real-time
      polymerase chain reaction were used. RESULTS: The BWC reached the first and
      second (highest) peaks at 6 and 72 hours, and the blood brain barrier (BBB) was
      severely destroyed at six hours after the TBI. The worst brain ischemia occurred
      at 72 hours after TBI. Widespread AQP9-positive astrocytes and neurons in the
      hypothalamus were detected by means of IHC and IF after TBI. The abundance of
      AQP9 and its mRNA increased after TBI and reached two peaks at 6 and 72 hours,
      respectively, after TBI. CONCLUSIONS: Increased AQP9 might contribute to
      clearance of excess water and lactate in the early stage of TBI. Widespread AQP9
      positive astrocytes might help lactate move into neurons and result in cellular
      brain edema in the later stage of TBI. AQP9-positive neurons suggest that AQP9
      plays a role in energy balance after TBI.

PMID- 22392117
TI  - Blood-brain barrier breakdown and repair following gliotoxic drug injection in
      the brainstem of streptozotocin-diabetic rats.
AB  - Ethidium bromide (EB) causes local astrocytic disappearance, with glia limitans
      disruption and blood-brain barrier (BBB) breakdown. The aim of this study was to
      evaluate the BBB integrity after the injection of 0.1% EB or 0.9% saline solution
      into the cisterna pontis of Wistar rats submitted or not to the streptozotocin
      diabetogenic model. Brainstem sections were collected from 24 hours to 31 days
      post-injection for ultrastructural analysis and glial fibrillary acidic protein
      immunohistochemical staining. Some animals received colloidal carbon ink by
      intravenous route at the same periods. In rats injected with EB, results revealed
      astrocyte disappearance and leakage of carbon particles beginning at 48 hours and
      persisting for 7 days in non-diabetic rats and for 15 days in the diabetic ones,
      although, in both groups, several areas remained devoid of astrocytic processes
      up to 31 days. In rats injected with saline, there was no sign of astrocytic loss
      or carbon particles leakage.

PMID- 22392118
TI  - Leukoencephalopathy with cerebral calcifications and cyst: Labrune syndrome.

PMID- 22392119
TI  - Metamorphopsia associated with topiramate for migraine prevention.

PMID- 22392120
TI  - Behavioral changes on amyotrophic lateral sclerosis (ALS): a case of ALS/FTD TDP
      43 proteinopathy.

PMID- 22392121
TI  - Central neurocytoma of spinal cord.

PMID- 22392122
TI  - Alcohol production in cryptococcal meningitis.

PMID- 22392123
TI  - Headache, alcoholic consumption, and medical student.

PMID- 22392124
TI  - Investigation of cognitive impairments in people with brain tumors.
AB  - Study of brain tumors (BT) has revealed the importance of cognitive and
      behavioral assessment to clinical care and prognosis. This paper overviews recent
      literature, focusing on the main points of interest and current methods,
      providing recommendations for advancing research. Histological aspects, disease
      progression, treatment-related neurotoxicity, and co-morbidities determine the
      cognitive patterns of BT. Mental slowing with prominent executive and memory
      compromise usually mark the advanced phases of disease, whereas normal cognitive
      performance or subtle behavioral symptoms characterize the early disease course,
      irrespective of tumor location. Neurocognitive assessment may indicate brain
      damage in otherwise neurologically normal patients, explain pathological
      behavior, and provide reliable measures of outcome, contributing to improving the
      management of patients. Scarce attention has been devoted to social cognitive
      deficits which are expected to impair autonomy and relationships. Interest in non
      pharmacological treatment of cognitive impairment is a growing area although
      methodological difficulties persist. Homogeneous patient populations,
      longitudinal study designs including baseline evaluations, and measurement of the
      lowest and highest levels of cognitive performance seem indispensable to
      advancing the study of the cognitive and behavioral changes provoked by BT.
      Future investigations are also expected to clarify the clinical significance of
      such changes, their effect on quality of life, and the efficacy of specific
      rehabilitation treatments.

PMID- 22392125
TI  - 1P19Q loss but not IDH1 mutations influences WHO grade II gliomas spontaneous
      growth.
AB  - Mutations at the codon 132 in the isocitrate dehydrogenase 1 (IDH1) gene occur
      early, with a high frequency, in World Health Organization (WHO) grade II
      gliomas. We investigated the impact of IDH1 mutations on spontaneous glioma
      growth rate, known to be an early prognostic factor.The mean tumor diameter was
      assessed on the first MRI performed at diagnosis and on a second MRI, performed
      immediately before surgery, in a series of 64 WHO grade II gliomas. The patients
      did not undergo treatment before surgery. Because of a frequent association, we
      jointly analyzed the 1p19q co-deletion and IDH1 mutations effects on tumor
      velocity of diameter expansion (mm/year) during preoperative spontaneous growth
      period. 1p19q co-deletion had a significant slowing effect (p = 0.0133) on tumor
      growth estimated at -1.7760 +/- 0.711 mm/year (95% CI -3.154, -0.366), whereas
      IDH1 mutations estimated effect of +0.036 +/- 0.833 mm/year (95% CI -1.668;
      +1.596) was not significant (p = 0.9654). Our results provide first evidence that
      IDH1 mutations are not significantly involved in tumor growth rate. By contrast,
      we confirm that 1p19q co-deletion decreases growth velocity.

PMID- 22392126
TI  - Significance of target location relative to the depth from the brain surface and
      high-dose irradiated volume in the development of brain radionecrosis after
      micromultileaf collimator-based stereotactic radiosurgery for brain metastases.
AB  - The objective of this study was to investigate the factors that potentially lead
      to brain radionecrosis (RN) after micromultileaf collimator-based stereotactic
      radiosurgery (SRS) for brain metastases. We retrospectively evaluated 131 lesions
      with a minimum follow-up of 6 months, 43.5% of which received prior whole-brain
      radiotherapy (WBRT). The three-tiered location grade (LG) was defined, as
      follows, for each target by considering mainly the depth from the brain surface:
      grade 1 (superficial), involving the region at a depth of <=5 mm from the brain
      surface; grade 2 (deep), located at a depth of >5 mm from the brain surface; and
      grade 3 (central), located in the brainstem, cerebellar peduncle, diencephalon,
      or basal ganglion. The predictive factors for RN, including high-dose irradiated
      isodose volumes (IIDVs) and LG, were evaluated by univariate and multivariate
      analysis. Symptomatic RN (S-RN) and asymptomatic RN (A-RN) were observed in 8.4%
      and 6.9% of cases, respectively. Multivariate analysis indicated that the
      significant factors for both types of RN were LG, V12 Gy, and V22 Gy in all
      cases; V22 Gy and LG for the non-WBRT cases; and V15 Gy and LG for the WBRT
      cases. For the non-WBRT cases, the cutoff values of V22 Gy were 2.62 and 2.14
      cm(3) for S-RN and both RN, respectively. For the WBRT cases, the cutoff values
      of V15 Gy were 5.61 and 5.20 cm(3) for S-RN and both RN, respectively. In
      addition to the IIDV data, LG helps predict the risk of RN. High-dose IIDV, V22
      Gy, was also significantly correlated with RN, particularly for patients treated
      with SRS alone.

PMID- 22392128
TI  - Induced mirror symmetry breaking via template-controlled copolymerization:
      theoretical insights.
AB  - A chemical equilibrium model of template-controlled copolymerization is presented
      for describing the outcome of the experimental induced desymmetrization scenarios
      recently proposed by Lahav and co-workers.

PMID- 22392130
TI  - Gluten-free diet in obese patients with celiac disease: an enemy of the bariatric
      surgeon?

PMID- 22392129
TI  - Laparoscopic treatment of obese patients with gastroesophageal reflux disease and
      Barrett's esophagus: a prospective study.
AB  - BACKGROUND: Short-segment Barrett's esophagus (SSBE) or long-segment Barrett's
      esophagus (LSBE) is the consequence of chronic gastroesophageal reflux disease
      (GERD), which is frequently associated with obesity. Obesity is a significant
      risk factor for the development of GERD symptoms, erosive esophagitis, Barrett's
      esophagus, and esophageal adenocarcinoma. Morbidly obese patients who submitted
      to gastric bypass have an incidence of GERD as high as 50% to 100% and Barrett's
      esophagus reaches up to 9% of patients. METHODS: In this prospective study, we
      evaluate the postoperative results after three different procedures--calibrated
      fundoplication + posterior gastropexy (CFPG), fundoplication + vagotomy + distal
      gastrectomy + Roux-en-Y gastrojejunostomy (FVDGRYGJ), and laparoscopic
      resectional Roux-en-Y gastric bypass (LRRYGBP)--among obese patients. RESULTS: In
      patients with SSBE who submitted to CFPG, the persistence of reflux symptoms and
      endoscopic erosive esophagitis was observed in 15% and 20.2% of them,
      respectively. Patients with LSBE were submitted to FVDGRYGJ or LRRYGBP which
      significantly improved their symptoms and erosive esophagitis. No modifications
      of LESP were observed in patients who submitted to LRRYGBP before or after the
      operation. Acid reflux diminished after the three types of surgery were employed.
      Patients who submitted to LRRYGBP presented a significant reduction of BMI from
      41.5 +/- 4.3 to 25.7 +/- 1.3 kg/m(2) after 12 months. CONCLUSIONS: Among patients
      with LSBE, FVDGRYGJ presents very good results in terms of improving GERD and
      Barrett's esophagus, but the reduction of weight is limited. LRRYGBP improves
      GERD disease and Barrett's esophagus with proven reduction in body weight and
      BMI, thus becoming the procedure of choice for obese patients.

PMID- 22392131
TI  - The psychology of obesity.
AB  - G. Stanley Hall, the first person to earn a Ph.D. in psychology in the United
      States, did research on eating behaviors in the nineteenth century (Lepore in The
      New Yorker, 2011). Research on psychological aspects of obesity accelerated in
      the 1950s and there has been a great deal done at this point. We review areas of
      considerable activity and relevance.

PMID- 22392132
TI  - The effect of sublethal exposure to temephos and propoxur on reproductive fitness
      and its influence on circadian rhythms of pupation and adult emergence in
      Anopheles stephensi Liston-a malaria vector.
AB  - The present study was undertaken to investigate the effects of organophosphate
      and carbamate insecticides namely, temephos and propoxur respectively, on the
      life history of Anopheles stephensi Liston (Culicidae) under laboratory
      conditions. The late third instar larvae of the mosquito were exposed to
      sublethal concentrations of temephos and propoxur at LC(10), LC(30) and LC(50),
      respectively, and adult survivors were evaluated for fitness parameters.
      Sublethal effects were also evaluated in subsequent generations. Fecundity, egg
      hatchability, sex ratio, adult longevity and morphology of gonads were the end
      points studied and compared to the untreated control. Adverse changes in
      developmental traits were mainly observed in fecundity, egg hatchability and sex
      ratio. However, significant differences in adult longevity were observed in the
      insecticide-exposed population. Pleiotropic effects through prolonged larval
      duration and enhanced longevity of adults were observed. Morphology of gonads in
      the insecticide-exposed population was severely affected and is represented by
      rudimentary and atrophied testes, and the size of the vas deferens was very much
      reduced when compared to that of the control. In another set of experiments,
      circadian rhythm (for pupation and adult emergence) of LC(10), LC(30) and LC(50)
      values to abovementioned insecticides exposed to late third instar larvae was
      studied. Pupation and adult emergence rhythms were found to be disturbed with an
      increase in concentrations of insecticides when compared to that of untreated
      control.

PMID- 22392133
TI  - Mitochondrial DNA and morphology show independent evolutionary histories of
      bedbug Cimex lectularius (Heteroptera: Cimicidae) on bats and humans.
AB  - The bedbug, Cimex lectularius, is a well-known human ectoparasite that is
      reemerging after a long absence of several decades in developed countries of
      North America and Western Europe. Bedbugs' original hosts were likely bats, and
      the bedbugs are still common in their roosts. Using morphometry and sequences of
      mitochondrial cytochrome oxidase subunit I and 16S genes, we showed that the
      populations on bats and humans are largely isolated and differ in morphology. The
      character of the morphological difference suggests it to be due to adaptation to
      different hosts, namely adaptations to different sensory, feeding, and dispersal
      needs. Using the molecular data, we estimated the time of splitting into bat- and
      human-parasitizing groups using the isolation-with-migration model. The estimate
      is surprisingly long ago and seems to predate the expansion of modern human from
      Africa. The gene flow between bat- and human-parasitizing bedbugs is limited and
      asymmetric with prevailing direction from human-parasitizing populations to bat
      parasitizing populations. The differentiation of the populations fits the concept
      of host races and supports the idea of sympatric speciation. Furthermore, our
      findings contradict recently formulated hypotheses suggesting bat roosts as a
      source of bedbug's resurgence as a human pest. Also, we extend the known host
      range of the bedbug by two bat species.

PMID- 22392134
TI  - Cloning and characterization of Plasmodium vivax thioredoxin peroxidase-1.
AB  - Reactive oxygen species produced from hemoglobin digestion and the host immune
      system could have adverse effects on malaria parasites. To protect themselves,
      malaria parasites are highly dependent on the antioxidant enzymes, including
      superoxide dismutases and thioredoxin-dependent peroxidases. To date, several
      thioredoxin peroxidases (TPx) have been characterized in Plasmodium falciparum,
      but the TPx in Plasmodium vivax has not yet been characterized. The complete
      sequence of gene coding for thioredoxin peroxidase-1 of P. vivax (PvTPx-1) was
      amplified by PCR and cloned. Using the recombinant PvTPx-1 (rPvTPx-1), polyclonal
      antibody was produced in mice for immunolocalization of the enzyme in the
      parasite. The antioxidant activity of rPvTPx-1 was evaluated by mixed-function
      oxidation assay. PvTPx-1 has two conserved cysteine residues in the amino acid
      sequence at the positions 50 and 170 which formed a dimer under a non-reducing
      condition. Using a thiol mixed-function oxidation assay, the antioxidant activity
      of rPvTPx-1 was revealed. Indirect immunofluorescence microscopy with the
      specific antibody indicated that PvTPx-1 was expressed in the cytoplasm of the
      erythrocytic stage of the parasite in a dots-like pattern. The results suggest
      that P. vivax uses TPx-1 to reduce and detoxify hydrogen peroxides in order to
      maintain their redox homeostasis and proliferation in the host body.

PMID- 22392136
TI  - Augmentation of antileishmanial efficacy of miltefosine in combination with
      tuftsin against experimental visceral leishmaniasis.
AB  - Current drugs for the treatment of visceral leishmaniasis are inadequate, and
      their efficacies are also compromised due to suppression of immune function
      during the course of infection. Miltefosine is the only promising orally active
      antileishmanial drug, but due to its long half-life, there is risk of development
      of resistance. To overcome these problems, efforts are needed to develop
      combination therapy of miltefosine with effective immunostimulating agents where
      a decrease of parasitic burden and simultaneous enhancement of adaptive immunity
      can be achieved. In the present study, we have explored the antileishmanial
      efficacy of a subcurative dose of miltefosine in combination with free as well as
      liposomal palmitoyl tuftsin (p-tuftsin) using a Leishmania donovani/BALB/c mouse
      model. When miltefosine (2.5 mg/kg for 5 days) was given with free p-tuftsin, the
      inhibitory effect was significantly increased from 49.6% to 66% (P < 0.01), which
      was further enhanced up to 81% (P < 0.001) when given after liposomal
      encapsulation of p-tuftsin. Significant enhancement in parasitic inhibition (93%,
      P < 0.01) was witnessed when animals were co-administered with liposomal p
      tuftsin + 5 mg/kg * 5 days dose of miltefosine (72.1%). Enhancement in the
      production of Th1 cytokines (IL-12, TNF-alpha, and IFN-gamma), reactive oxygen,
      and nitrogen metabolites was witnessed in the combination group. A remarkable
      increase in phagocytosis index was also observed indicating overall immunological
      enhancement to antileishmanial activity of miltefosine by p-tuftsin.

PMID- 22392135
TI  - Validity of silver, chitosan, and curcumin nanoparticles as anti-Giardia agents.
AB  - This study was carried out to evaluate the anti parasitic potential of silver,
      chitosan, and curcumin nanoparticles as anti-Giardia agents. Non-treated infected
      control rats were inoculated with Giardia lamblia cysts in a dose of 2 * 10(5)
      cysts/rat. Experimental group was infected then treated with curcumin, curcumin
      nanoparticles, chitosan, chitosan nanoparticles, and silver nanoparticles as
      single or combined therapy. The number of Giardia cysts in stools and
      trophozoites in intestinal sections were detected. Toxicity of nanoparticles was
      evaluated by comparing hematological and histopathological parameters of the
      normal control group and treated non-infected control group. The amount of silver
      was also measured in the liver, kidney, small intestine, lung, and brain of rats
      treated with silver nanoparticles. The number of the parasites in stool and small
      intestinal sections decreased in treated infected rats compared with infected non
      treated ones. The effect in the single therapy was better with nanoparticles, and
      the best effect was detected in nano-silver. The combined therapy gave better
      results than single. Combination between nanoparticles was better than the
      combination of nano-forms and native chitosan and curcumin. The best effect was
      detected in combinations of nano-silver and nano-chitosan but with no full
      eradication. In conclusion, the highest effect and complete cure was gained by
      combining the three nano-forms. The parasite was successfully eradicated from
      stool and intestine. None of the treatments exhibited any toxicity. Accumulated
      silver in different organs was within the safe limits.

PMID- 22392137
TI  - Using the AD12-ICT rapid-format test to detect Wuchereria bancrofti circulating
      antigens in comparison to Og4C3-ELISA and nucleopore membrane filtration and
      microscopy techniques.
AB  - Lymphatic filariasis (LF) continues to be a major source of permanent disability
      and an impediment to socio-economic development in 73 countries where more than 1
      billion people are at risk and over 120 millions are infected. The global drive
      to eliminate LF necessitates an increasing demand for valid, reliable and rapid
      diagnostic tests. This study aimed to assess the performance of the AD12 rapid
      format immunochromatographic test (ICT) to detect Wuchereria bancrofti
      circulating antigens, against the combined gold standard: TropBio Og4C3-ELISA
      (enzyme-linked immunosorbent assay) which detects circulating filarial antigen
      (CFA) and the nucleopore membrane filtration and microscopic examination. This
      prospective case-control study involved 647 asymptomatic migrant workers from
      filariasis-endemic countries. Of these specimens, 32 were positive for
      microfilaremia using the membrane filtration and microscopy, 142 positive by
      ELISA (of which 32 had microfilaremia), and 128 positive by the ICT (of which 31
      had microfilaremia). The performance of the ICT was calculated against 32 true
      positive and 90 true-negative cases. For the detection of CFA, the ICT had a
      sensitivity of 97% (95% confidence interval [CI] 91-103), specificity 100% (95%
      CI 100-100), Positive Predictive Value (PPV) 100% (95% CI 100-100), Negative
      Predictive Value (NPV) 99% (95% CI 97-101); and the total accuracy of the test
      was 99% (95% CI 98-101). The agreement between ICT and ELISA in detecting W.
      bancrofti antigens was excellent (kappa = 0.934; p = 0.000). In conclusion, the
      AD12-ICT test for the detection of W. bancrofti-CFA was sensitive and specific
      and comparable to the performance of ELISA. The ICT would be a useful additional
      test to facilitate the proposed strategies for control and elimination of LF.
      Because it is rapid, simple to perform, and does not require the use of special
      equipment, the ICT may be most appropriate in screening programs and in
      monitoring the possible risk of introducing the disease to the non-endemic
      countries.

PMID- 22392138
TI  - The course of a primary infection of Plasmodium yoelii 17XL in both 129S1 and IFN
      gamma receptor-deficient mice.
AB  - In the present study, we found that 129S1 mice are resistant to the infection
      with Plasmodium yoelii 17XL, which is highly virulent and causes lethal infection
      in various strains of mice. In contrast, IFN-gamma receptor-deficient (IFN
      gammaR(-/-)) mice on the 129S1 background were much more susceptible than 129S1
      mice with intraperitoneal infection with 1 * 10(5) parasitized erythrocytes. The
      mortality in 129S1 and IFN-gammaR(-/-) mice was 11.6 and 79.4 %, respectively.
      Following inoculation of the parasites, both 129S1 and IFN-gammaR(-/-) mice
      showed a progressive increase in parasitemia. Growth rate of malaria parasites at
      the early stages of infection in the IFN-gammaR(-/-) mice was faster than that in
      129S1 mice, and this difference in growth rate might cause the earlier death of
      IFN-gammaR(-/-) host from day 8 of infection than that of 129S1. In surviving
      mice of both strains, however, malaria parasites in their bloodstream began to
      decrease in number right after a peak of parasitemia and were not detectable by a
      microscopic examination during the observation period. Next, we investigated the
      cytokine and antibody production in 129S1 and IFN-gammaR(-/-) mice during
      infection. An analysis of cytokines showed that serum IFN-gamma and IL-4 levels
      elevated significantly from day 1 and day 4 of infection, respectively, in both
      129S1 and IFN-gammaR(-/-) mice when compared with the levels from the uninfected
      controls. Following the infection, significantly higher levels of malaria
      specific IgG1 and IgG2a antibodies in the infected 129S1 mice were detected from
      day 15, and these elevations were coincident with the decrease of parasitemia. On
      the other hand, the levels of malaria-specific antibodies in IFN-gammaR(-/-) mice
      had a tendency to elevate on day 21 but did not reach statistical significance.
      The present data indicate that IFN-gammaR plays an essential role in mediating
      the early immune mechanisms induced by the infection of erythrocytic stages of P.
      yoelii 17XL parasite, leading to host survival.

PMID- 22392139
TI  - Detection and characterization of Cryptosporidium cuniculus by real-time PCR.
AB  - Cryptosporidium cuniculus was originally detected in rabbits and has been
      identified as an emerging human pathogen, but the occurrence, prevalence, and
      epidemiology in human and rabbit populations are poorly understood. As
      identification of C. cuniculus can be time-consuming and costly using existing
      molecular assays, a real-time polymerase chain reaction (PCR)-based method
      targeting specific markers for this species was developed. The assay is based on
      amplification of the C. cuniculus-specific 60-kDa glycoprotein (GP60) gene using
      two PCRs targeting subtype families Va and Vb. PCR product formation was
      monitored by SYBR Green I fluorescence measurement followed by post-amplification
      melt curve analysis; high resolution melt curve analysis was found to give
      increased sensitivity over standard melt curve analysis. The real-time PCR
      correctly identified all 41 C. cuniculus isolates (40 from humans, one from a
      rabbit) tested, with subtype family in agreement with GP60 gene sequencing.
      Specificity was demonstrated by lack of detection of nine other Cryptosporidium
      species and genotypes, including 88 isolates of the closely related species,
      Cryptosporidium hominis. The PCRs were performed in separate tubes to maximize
      the possibility of detecting mixed Va-Vb infections; however, none were detected.
      The potential for multiplexing the reactions was also demonstrated, furthering
      the utility of the assay for large-scale occurrence and prevalence studies.

PMID- 22392140
TI  - Associations among parent acculturation, child BMI, and child fruit and vegetable
      consumption in a Hispanic sample.
AB  - The objective of this study was to investigate the association of parent
      acculturation with child fruit and vegetable consumption and obesity, as measured
      by body mass index (BMI). Participants included 250 Mexican-American and other
      Hispanic families living within San Diego County. Height and weight measurements
      were collected to calculate the age- and sex-specific BMI for each child and
      parent, and parents completed self-administered surveys. Child BMI z-score was
      significantly related to parent BMI after controlling for parent acculturation
      and parent birth place (beta = 0.05, p < 0.01). Child fruit consumption was
      significantly associated with parent acculturation (beta = -0.02, p = 0.01) and
      parent BMI (beta = 0.02, p = 0.04) after adjusting for the other variables in the
      model. Child vegetable consumption was not significantly related to parent
      acculturation. Findings suggest that parental weight status may be more
      predictive of child obesity than acculturation, and highlight the need to examine
      culturally relevant behavioral and psychosocial factors related to childhood
      obesity and dietary behaviors.

PMID- 22392141
TI  - Managing methanogens and homoacetogens to promote reductive dechlorination of
      trichloroethene with direct delivery of H2 in a membrane biofilm reactor.
AB  - A study with H(2)-based membrane biofilm reactors (MBfRs) was undertaken to
      examine the effectiveness of direct H(2) delivery in ex-situ reductive
      dechlorination of chlorinated ethenes. Trichloroethene (TCE) could be reductively
      dechlorinated to ethene with up to 95% efficiency as long as the pH-increase
      effects of methanogens and homoacetogens were managed and dechlorinators were
      selected for during start-up by creating H(2) limitation. Based on quantitative
      PCR, the dominant bacterial groups in the biofilm at the end of reactor operation
      were Dehalococcoides, Geobacter, and homoacetogens. Pyrosequencing confirmed the
      dominance of the dechlorinators and identified Acetobacterium as the key
      homoacetogen. Homoacetogens outcompeted methanogens for bicarbonate, based on the
      effluent concentration of acetate, by suppressing methanogens during batch start
      up. This was corroborated by the methanogenesis functional gene mcrA, which was 1
      2 orders of magnitude lower than the FTHFS functional gene for homoacetogens.
      Imaging of the MBfR fibers using scanning electron microscopy showed a distinct
      Dehalococcoides-like morphology in the fiber biofilm. These results support that
      direct addition of H(2) can allow for efficient and complete reductive
      dechlorination, and they shed light into how H(2)-fed biofilms, when operated to
      manage methanogenic and homoacetogenic activity, can be used for ex-situ
      bioremediation of chlorinated ethenes.

PMID- 22392142
TI  - NADPH oxidase-derived superoxide destabilizes lipopolysaccharide-induced
      interleukin 8 mRNA via p38, extracellular signal-regulated kinase mitogen
      activated protein kinase, and the destabilizing factor tristetraprolin.
AB  - Expression of inflammatory cytokines is regulated by transcriptional and
      posttranscriptional mechanisms. We previously showed that NADPH oxidase-derived
      superoxide induces inflammatory mediators in response to tumor necrosis factor
      alpha (TNF-alpha) and lipopolysaccharide (LPS). In this study, we examined the
      role of endothelial NADPH oxidase in the regulation of mRNA stability of three
      inflammatory mediators: interleukin (IL) 8, IL-6, and intercellular adhesion
      molecule 1 (ICAM-1). Tumor necrosis factor alpha increased mRNA stability of ICAM
      1, IL-8, and IL-6 by a p38 mitogen-activated protein kinase (MAPK)-dependent
      mechanism, but this did not involve NADPH oxidase. Surprisingly, whereas LPS
      treatment alone did not alter stability of these molecules, the antioxidant N
      acetyl-L-cysteine; the flavine inhibitor diphenylene iodonium; short interfering
      RNA against Nox2, Nox4; and the p22(phox) subunit of NADPH oxidase all enhanced
      IL-8 mRNA stability in LPS-treated cells, indicating that LPS induced
      destabilization through NADPH oxidase. This occurred by a mechanism that involved
      extracellular signal-regulated kinase 1/2, p38 MAPK, and the mRNA-destabilizing
      factor tristetraprolin. On the other hand, N-acetyl-L-cysteine decreased mRNA
      stability of ICAM-1 and IL-6 in LPS-treated cells and IL-6 and ICAM-1 in TNF
      alpha-treated cells. In conclusion, NADPH oxidase contributes to destabilization
      of IL-8 mRNA stability and propose a model for the complex underlying mechanism,
      which is dependent upon agonist (LPS vs. TNF-alpha) and target molecule (IL-8 vs.
      IL-6 and ICAM-1) and involves tristetraprolin, p38, and extracellular signal
      regulated kinase 1/2 MAPK.

PMID- 22392143
TI  - Specific role of neutrophil inducible nitric oxide synthase in murine sepsis
      induced lung injury in vivo.
AB  - Nitric oxide produced by inducible nitric oxide synthase (iNOS) contributes
      importantly to acute lung injury (ALI), but the specific contribution of
      neutrophil iNOS has not been defined. Thus, we defined the role of neutrophils
      and specifically neutrophil iNOS in a murine model of septic ALI. Four hours
      after cecal ligation/perforation, ALI was characterized by increases in pulmonary
      neutrophil infiltration (tissue myeloperoxidase activity, bronchoalveolar lavage
      neutrophils), microvascular leak of Evans blue (EB) dye-labeled albumin, and
      oxidant stress (8-isoprostane levels). Septic ALI was neutrophil dependent, as
      pretreatment with anti-CD18 before cecal ligation/perforation significantly (P <
      0.05) attenuated septic increases in pulmonary myeloperoxidase (39 +/- 11 vs. 85
      +/- 14 mU/mg protein), bronchoalveolar lavage neutrophils (0.5% +/- 0.2% vs. 2.1%
      +/- 0.6%), microvascular EB-albumin leak (1.3 +/- 0.3 vs. 2.6 +/- 0.7 MUg EB/g
      per minute), and 8-isoprostane content (74 +/- 15 vs. 115 +/- 16 pg/mg protein).
      The role of neutrophil iNOS was assessed by creation of neutrophil-iNOS chimeric
      mice: iNOS(+/+) versus iNOS(-/-) mice were bone marrow depleted by irradiation
      and selectively reconstituted with iNOS(+/+) versus iNOS(-/-) neutrophils. Cecal
      ligation/perforation resulted in significant septic ALI in + to - neutrophil-iNOS
      chimeric mice (iNOS(+/+) neutrophils in iNOS(-/-) mice), but not in - to +
      neutrophil depleted-reconstituted mice (iNOS(-/-) neutrophils in iNOS(+/+) mice).
      There were no significant differences between iNOS(+/+) and iNOS(-/-) neutrophils
      in phagocytosis, respiratory burst, or CD11a/b/CD18 surface expression, although
      septic shedding of CD62L was blunted in iNOS(-/-) neutrophils. Neutrophil iNOS
      contributes importantly to murine septic ALI in vivo, but not simply through a
      change in neutrophil phenotype. We speculate that neutrophil iNOS may modulate
      neutrophil-endothelial interactions in complex fashion, including regulation of
      transendothelial neutrophil migration and pulmonary neutrophil infiltration.

PMID- 22392144
TI  - Effects of eritoran tetrasodium, a toll-like receptor 4 antagonist, on intestinal
      microcirculation in endotoxemic rats.
AB  - Lipopolysaccharide (LPS) or endotoxin can induce Toll-like receptor 4 signaling
      and cause microcirculatory dysfunction, which can lead to multiple organ
      dysfunction. The goal of this study was to investigate whether Toll-like receptor
      4 antagonist, eritoran tetrasodium, can attenuate microcirculatory dysfunction in
      endotoxemic rats. Seventy-two male Wistar rats were divided into three groups as
      follows: control, LPS, and eritoran + LPS. These rats received laparotomy to
      exteriorize a segment of terminal ileum for microcirculation examination on
      intestinal mucosa, muscle, and Peyer patch. The rats in the eritoran + LPS group
      received 10 mg kg-1 eritoran intravenously. The rats in the LPS and eritoran +
      LPS groups received 15 mg kg-1 LPS intravenously. Microcirculatory blood flow
      intensity was measured by full-field laser perfusion imager. Total and perfused
      small-vessel densities, microvascular flow index, and heterogeneity index were
      investigated by sidestream dark-field video microscope. Our results revealed that
      eritoran restored the mean arterial pressure. At 240 min, the microcirculatory
      blood flow intensity was higher in the eritoran + LPS group than in the LPS group
      as follows: mucosa (1,094 [SD, 398] vs. 543 [SD, 163] perfusion unit [PU]; P <
      0.001), muscle (752 [SD, 124] vs. 357 [SD, 208] PU; P < 0.001), and Peyer patch
      (961 [SD, 162] vs. 480 [SD, 201] PU; P < 0.001). Eritoran also attenuated
      endotoxin-induced elevation in the serum level of D-dimer. In conclusion, we have
      established a promising rat protocol to investigate the intestinal
      microcirculation in endotoxemia. Our data indicate that eritoran can reduce
      microcirculatory dysfunction in endotoxemic rats.

PMID- 22392145
TI  - Acute treatment with bone marrow-derived mononuclear cells attenuates the organ
      injury/dysfunction induced by hemorrhagic shock in the rat.
AB  - Recent evidence suggests that cell therapy such as the injection of bone marrow
      derived mononuclear cells (BMMNCs) can exert protective effects in various
      conditions associated with ischemia-reperfusion injury. Here, we investigate the
      effects of BMMNCs on the organ injury/dysfunction induced by hemorrhagic shock
      (HS). Thirty-seven anesthetized male Wistar rats were subjected to hemorrhage by
      reducing mean arterial pressure to 35 +/- 5 mmHg for 90 min, followed by
      resuscitation with 20 mL/kg Ringer's lactate administered over 10 min and 50% of
      the shed blood over 50 min. Rats were killed 4 h after the onset of
      resuscitation. Bone marrow-derived mononuclear cells were freshly isolated from
      rat tibias and femurs using Percoll density gradient centrifugation, and BMMNCs
      (1 * 10 cells per rat in 1 mL/kg phosphate-buffered saline, i.v.) were
      administered on resuscitation. Hemorrhagic shock resulted in significant organ
      injury/dysfunction (renal, hepatic, neuromuscular) and inflammation (hepatic,
      lung). In rats subjected to HS, administration of BMMNCs significantly attenuated
      (i) organ injury/dysfunction (renal, hepatic, neuromuscular) and inflammation
      (hepatic, lung), (ii) increased the phosphorylation of Akt and glycogen synthase
      kinase-3beta, (iii) attenuated the activation of nuclear factor-kappaB, (iv)
      attenuated the increase in extracellular signal-regulated kinase 1/2
      phosphorylation, and (v) attenuated the increase in expression of intercellular
      adhesion molecule-1. Our findings suggest that administration of BMMNCs protects
      against the induction of early organ injury/dysfunction caused by severe HS by a
      mechanism that may involve activation of Akt and the inhibition of glycogen
      synthase kinase-3beta and nuclear factor-kappaB.

PMID- 22392146
TI  - Effect of hydrogen gas on the survival rate of mice following global cerebral
      ischemia.
AB  - Global cerebral ischemia and reperfusion (I/R) often result in high mortality.
      Free radicals have been reported to play an important role in global cerebral
      I/R, and therefore, reduction of these might improve the outcome. Here, we
      investigated the effect of hydrogen gas (H2) (a strong free radical scavenger) on
      the survival rate of mice following global cerebral I/R. We further examined the
      histopathological outcome and also the brain water content (as a possible
      determinant of mortality). Male C57BL/6J mice were subjected to global cerebral
      I/R by means of 45-min bilateral common carotid artery occlusion (BCCAO). A total
      of 160 mice were divided into three groups: sham surgery (sham group), BCCAO
      without H2 (BCCAO group), and BCCAO treated with 1.3% H2 (BCCAO + H2 group). We
      observed that H2 treatment significantly (P = 0.0232) improved the 7-day survival
      rate of mice, from 8.3% (BCCAO group, n = 12) to 50% (BCCAO + H2 group, n = 10).
      Histopathological analysis revealed that H2 treatment significantly attenuated
      neuronal injury and autophagy in the hippocampal cornu ammonis 1 sector and also
      brain edema, after 24 h of reperfusion. The beneficial effects of H2 treatment on
      brain injury were associated with significantly lower levels of oxidative stress
      markers (8-hydroxy-2'-deoxyguanosine and malondialdehyde) in the brain tissue.
      Thus, we believe that H2 may be an effective treatment for global cerebral I/R.

PMID- 22392147
TI  - Systemic involvement of high-mobility group box 1 protein and therapeutic effect
      of anti-high-mobility group box 1 protein antibody in a rat model of crush
      injury.
AB  - Patients with crush injury often present systemic inflammatory response syndrome
      and fall into multiple organ failure. The mechanism by which the local tissue
      damage induces distant organ failure is still unclear. We focused on high
      mobility group box 1 protein (HMGB1) as one of the damage-associated molecular
      pattern molecules that cause systemic inflammation in crush injury. We
      investigated involvement of HMGB1 and the effects of treatment with anti-HMGB1
      antibody in a rat model of crush injury. Both hindlimbs of rats were compressed
      for 6 h and then released. In the crush injury group, the level of serum HMGB1
      peaked at 3 h after releasing compression, followed by the increasing in the
      serum levels of interleukin 6 and tumor necrosis factor alpha. Hematoxylin-eosin
      staining showed substantial damage in the lung 24 h after the crush injury, with
      upregulation of the expression of receptor for advanced glycation end products,
      as revealed by immunohistochemical analysis. Intravenous administration of anti
      HMGB1 antibody improved survival (n = 20 each group) and significantly suppressed
      serum levels of HMGB1, interleukin 6, and tumor necrosis factor alpha compared
      with the untreated crush injury group (n = 6-9 each group). Histological findings
      of lung damage were ameliorated, and the expression of receptor for advanced
      glycation end products was hampered by the treatment. These results indicate that
      HMGB1 is released in response to damage immediately after crush injury and acts
      as a proinflammatory mediator. Administration of anti-HMGB1 antibody reduced
      inflammatory reactions and improved survival by blocking extracellular HMGB1.
      Thus, HMGB1 appears to be a therapeutic target, and anti-HMGB1 antibody may
      become a promising novel therapy against crush injury to prevent the progression
      to multiple organ failure.

PMID- 22392148
TI  - Pulmonary contusion is associated with toll-like receptor 4 upregulation and
      decreased susceptibility to pseudomonas pneumonia in a mouse model.
AB  - Pulmonary contusion is a major cause of respiratory failure in trauma patients.
      This injury frequently leads to immune suppression and infectious complications
      such as pneumonia. The mechanism whereby trauma leads to an immune-suppressed
      state is poorly understood. To further study this phenomenon, we developed an
      animal model of pulmonary contusion (PC) complicated by pneumonia and assessed
      the effect of PC and pneumonia on toll-like receptor expression in alveolar
      macrophages. Using a mouse model, PC was induced on the right lung, and pneumonia
      was induced with Pseudomonas aeruginosa (Pa) injected intratracheally 48 h after
      injury. Susceptibility to pneumonia was assessed by mortality at 7 days.
      Uninjured animals were used as controls. Bronchoalveolar lavage fluid and blood
      were assayed 48 h after injury and 24 h after Pa instillation to look at markers
      of systemic inflammation. Toll-like receptor expression in the initial
      inflammatory response was analyzed by flow cytometry. Unexpectedly, injured
      animals subjected to intratracheal injection of Pa at 48 h after PC demonstrated
      increased survival compared with uninjured animals. Bronchoalveolar lavage
      cytokine expression was increased significantly after Pa administration but not
      after PC alone. Toll-like receptor 4 expression on alveolar macrophages was
      significantly elevated in the injured group compared with sham but not in
      neutrophils. Animals subjected to PC are more resistant to mortality from
      infection with Pa and display an enhanced cytokine response when subsequently
      subjected to Pa. Increased expression of toll-like receptor 4 on alveolar
      macrophages and enhanced innate immunity are a possible mechanism of increased
      cytokine production and decreased susceptibility to pneumonia.

PMID- 22392149
TI  - The 5-lipoxygenase pathway is required for acute lung injury following
      hemorrhagic shock.
AB  - The cellular and biochemical mechanisms leading to acute lung injury (ALI) and
      subsequent multiple organ failure are only partially understood. To study the
      potential role of eicosanoids, particularly leukotrienes, as possible mediators
      of ALI, we used a murine experimental model of ALI induced by hemorrhagic shock
      after blood removal via cardiac puncture. Neutrophil sequestration, as shown by
      immunofluorescence and protein leakage into the alveolar space were measured as
      markers of injury. We used liquid chromatography coupled to tandem mass
      spectrometry to unequivocally identify several eicosanoids in the bronchoalveolar
      lavage fluid of experimental animals. MK886, a specific inhibitor of the 5
      lipoxygenase (5-LO) pathway, and transgenic mice deficient in 5-LO were used to
      determine the role of this enzymatic pathway in this model. Leukotriene B4 and
      leukotriene C4 were consistently elevated in shock-treated mice compared with
      sham-treated mice. MK886 attenuated neutrophil infiltration and protein
      extravasation induced by hemorrhagic shock. 5-Lipoxygenase-deficient mice showed
      reduced neutrophil infiltration and protein extravasation after shock treatment,
      indicating greatly reduced lung injury. These results support the hypothesis that
      5-LO, most likely through the generation of leukotrienes, plays an important role
      in the pathogenesis of ALI induced by hemorrhagic shock in mice. This pathway
      could represent a new target for pharmacological intervention to reduce lung
      damage following severe primary injury.

PMID- 22392150
TI  - Common variants in the TPH2 promoter confer susceptibility to paranoid
      schizophrenia.
AB  - Serotonergic system-related genes may be good candidates in investigating the
      genetic basis of schizophrenia. Our previous study suggested that promoter region
      of tryptophan hydroxylase 2 gene (TPH2) may confer the susceptibility to paranoid
      schizophrenia. In this study, we investigated whether common variants within TPH2
      promoter may predispose to paranoid schizophrenia in Han Chinese. A total of 509
      patients who met DSM-IV criteria for paranoid schizophrenia and 510 matched
      healthy controls were recruited for this study. Five polymorphisms within TPH2
      promoter region were tested. No statistically significant differences were found
      in allele or genotype frequencies between schizophrenic patients and healthy
      controls. The frequency of the rs4448731T-rs6582071A-rs7963803A-rs4570625T
      rs11178997A haplotype was significantly higher in cases compared to the controls
      (P = 0.003; OR = 1.49; 95% CI, 1.15-1.95). Our results suggest that the common
      variants within TPH2 promoter are associated with paranoid schizophrenia in Han
      Chinese. Further studies in larger samples are warranted to elucidate the role of
      TPH2 in the etiology of paranoid schizophrenia.

PMID- 22392151
TI  - Increased expression of alpha-synuclein by SNCA duplication is associated with
      resistance to toxic stimuli.
AB  - Duplication of alpha-synuclein gene (SNCA) is a recognized cause of Parkinson's
      disease (PD). However, the penetrance in families with SNCA duplication is as low
      as 30%, indicating that factors other than the SNCA gene dosage have an important
      role in neuronal death. In this study, using lymphoblastoid cell lines (LCLs)
      derived from a parkinsonian kindred with SNCA duplication, we examined whether
      there is difference in (1) the level of SNCA mRNA and protein expression and cell
      viability and (2) the vulnerability to various insults relevant to PD between a
      patient, asymptomatic carrier, and unaffected control. Expression of SNCA mRNA
      and protein increased in the LCLs from subjects with SNCA gene duplication,
      irrespective of the disease status. In the absence of treatment, LCLs from the
      patient and carrier showed decreased viability compared with the LCL from the
      control. The LCL from the patient also showed decreased viability compared to the
      carrier. When susceptibility to various insults including lactacystin,
      dexamethasone, 3-methyladenine, H(2)O(2), and rotenone was examined,
      surprisingly, the LCL from the patient was more resistant than the LCL from the
      control to all agents except for lactacystin. This study shows that both
      intrinsic and extrinsic factors and their interaction have important roles in
      cell death and in the development of PD and further indicates that the
      relationship between cell death and the level of alpha-synuclein may be more
      complicated than previously thought.

PMID- 22392152
TI  - Blood-borne metabolic factors in obesity exacerbate injury-induced gliosis.
AB  - Reactive gliosis, a sign of neuroinflammation, has been observed in mice with
      adult-onset obesity as well as CNS injury. The hypothesis that obesity-derived
      metabolic factors exacerbate reactive gliosis in response to mechanical injury
      was tested here on cultured primary glial cells subjected to a well-established
      model of scratch wound injury. Cells treated with serum from mice with diet
      induced obesity (DIO) showed higher immunoreactivity of CD11b (marker for
      microglia) and GFAP (marker for astrocytes), with morphological changes at both
      the injury border and areas away from the injury. The effect of DIO serum was
      greater than that of scratch injury alone. Leptin was almost as effective as DIO
      serum in inducing microgliosis and astrogliosis in a dose-response manner. By
      contrast, C-reactive protein (CRP) mainly induced microgliosis in noninjured
      cells; injury-induced factors appeared to attenuate this effect. The effect of
      CRP also differed from the effect of the antibiotic minocycline. Minocycline
      attenuated the microgliosis and to a lesser extent astrogliosis, particularly in
      CRP-treated cells, thus serving as a negative control. We conclude that blood
      borne proinflammatory metabolic factors in obesity increase reactive gliosis and
      probably exacerbate CNS injury.

PMID- 22392153
TI  - Metabolism: an Akt-independent pathway for regulation of gluconeogenesis.

PMID- 22392154
TI  - A review of the evidence for and against increased mortality in hypothyroidism.
AB  - The lifetime risk of overt hypothyroidism is around 5%, and this disease is
      usually preceded by subclinical hypothyroidism, which has an even higher
      prevalence (estimated to be up to 9%). Hypothyroidism has been linked with
      cardiac dysfunction, atherosclerosis, hypertension and coagulopathy. Intuitively,
      this increased morbidity is expected to shorten patients' lifespan, but
      definitive data are lacking on whether either of these hypothyroid states
      (particularly overt hypothyroidism) increase mortality. Study findings are
      inconsistent and, overall, the pooled data do not demonstrate increased mortality
      in patients with either subclinical or overt hypothyroidism. However, none of the
      available studies was adequately designed to answer this question. This Review
      discusses major shortcomings in those studies, such as population
      dissimilarities, hypothyroid state classification and misclassification, the
      inclusion of nonthyroidal illness, drug interference from concurrent therapies,
      serious comorbidities (for example, cardiovascular disease), differences in
      duration of follow-up and the number of levothyroxine-treated individuals. Taken
      together, the data exhibit little evidence of systematic bias and no strong
      scientific proof of increased mortality related to either subclinical or overt
      hypothyroidism. Future studies, however, should take the above-mentioned
      shortcomings and potential genetic confounding into consideration.

PMID- 22392156
TI  - Substance use and sexual risk behavior in HIV-positive men who have sex with men:
      an episode-level analysis.
AB  - Men who have sex with men (MSM) make up nearly half of all people living with HIV
      in the United States. The prevalence of the epidemic in this population makes it
      vitally important to understand the transmission of the infection and to develop
      methods to prevent its spread. The current study uses longitudinal diary methods
      to examine relationships between substance use and unprotected anal intercourse
      in a sample of 158 HIV-positive, mostly ethnic minority MSM. Results indicate
      that both general substance use and use of specific drugs (i.e., inhalants,
      cocaine, crack, and club drugs) have a substantial impact on the sexual risk
      behavior of this population.

PMID- 22392155
TI  - Understanding heterosexual condom use among homeless men.
AB  - This study uses an event-based approach to examine individual, relationship, and
      contextual correlates of heterosexual condom use among homeless men. Structured
      interviews were conducted with a predominantly African American sample of 305 men
      recruited from meal lines in the Skid Row area of Los Angeles. Men reported on
      their most recent heterosexual event involving vaginal or anal intercourse.
      Adjusting for demographic characteristics only, condom use was more likely when
      men had higher condom use self-efficacy, greater HIV knowledge, or talked to
      their partner about condoms prior to sex. Condom use was less likely when men
      held more negative attitudes towards condoms, the partner was considered to be a
      primary/serious partner, hard drug use preceded sex, or sex occurred in a public
      setting. Condom attitudes, self-efficacy, partner type, and communication were
      the strongest predictors of condom use in a multivariate model that included all
      of the above-mentioned factors. Associations of unprotected sex with hard drug
      use prior to sex and having sex in public settings could be accounted for by
      lower condom self-efficacy and/or less positive condom attitudes among men having
      sex under these conditions. Results suggest that it may be promising to adapt
      existing, evidence-based IMB interventions for delivery in non-traditional
      settings that are frequented by men experiencing homelessness to achieve HIV risk
      reduction and thus reduce a significant point of disparity for the largely
      African American population of homeless men.

PMID- 22392157
TI  - Measuring adherence to antiretroviral treatment: the role of pharmacy records of
      drug withdrawals.
AB  - This study aimed to evaluate adherence to antiretroviral treatment (ART) among
      HIV + adults, assess its association with HIV viral load (VL) and identify
      factors associated to adherence. A survey involving a random sample of adults
      followed at a HIV/AIDS reference center in Sao Paulo city, Brazil, from 2007 to
      2009 was done. A questionnaire was applied and data were retrieved from the
      pharmacy and medical records. The study involved 292 subjects: 70.2% men; median
      age: 43 years; median duration of ART: 8 years. 89.3% self-reported taken all
      prescribed pills in the last 3 days but only 39.3% picked up >=95% of the
      prescribed ART from the pharmacy in the last 12 months. At the multivariate
      analysis having symptoms prior to ART, taking fewer ART pills, and not missing
      medical appointments were independently associated to higher adherence. Adherence
      was strongly associated with undetectable HIV VL. Rates of undetectable HIV VL
      did not differ from 80 to >=95% of adherence.

PMID- 22392158
TI  - Prevalence and predictors of conscious risk behavior among San Franciscan men who
      have sex with men.
AB  - We estimated the prevalence of conscious risk, specifically defined as
      unprotected anal intercourse with an HIV-serodiscordant partner, and identified
      individual-level and partnership-level predictors of this behavior. Conscious
      risk was estimated to be practiced by 4.8% of HIV-negative MSM and 15.7% of HIV
      positive MSM over a six-month period (p < 0.01). Among HIV-negative MSM, episodes
      of conscious risk were estimated to be more frequent among individuals between
      the ages of 18 and 24 (compared to those 55 years of age or older), among African
      Americans and Whites (compared to Latinos and Asians), individuals earning less
      than 10,000 dollars per year (compared to those earning 50,000 and 70,000 dollars
      per year), and among users of methamphetamine, downers, pain killers, and amyl
      nitrate (poppers). Among HIV-positive MSM, episodes of conscious risk were more
      frequent among Whites and Asians (compared to those of "other" races, i.e., those
      of mixed race, or those who did not exclusively self-report as White, Black,
      Latino, or Asian), those with full-time employment (as opposed to those with part
      time employment), those earning between 30,000 and 50,000 dollars per year or
      70,000 dollars per year or greater (compared to those earning under 10,000
      dollars per year), and recent users of poppers. Conscious risk was more
      frequently reported in partnerships with large age gaps and in main partnerships
      (as opposed to casual or exchange partnerships). Individuals at high risk for
      conscious risk may be ideal candidates for pre-exposure prophylaxis (PrEP).

PMID- 22392159
TI  - The influence of drug consumption on condom use and other aspects related to HIV
      infection among male sex workers in Spain.
AB  - Higher rates of substance use have been associated with unsafe sex behavior. Male
      sex workers (MSW) present high rates of drug use during or after the professional
      sexual exchange with clients and also in their leisure. This research describes
      patterns of drug consumption among MSW in Spain and explores both the effect of
      substance use on professional and risk sexual behaviors. Participants were 100
      agency MSW offering their services in Valencia and Castellon (Spain). Most of
      them were drug users and the most common substances were "soft drugs" and
      cocaine. An absence of injection drugs was found. Drug consumers indicated a
      higher HIV risk perceived and lower perceived influence of substance use on
      condom use negotiation. Drug influence on condom use is not clear. More
      investigation about drug influence on sexual risk behaviors among MSW is needed.
      The role of steady partners and clients must be taken into account too.

PMID- 22392160
TI  - Reduced colon cancer incidence and mortality in postmenopausal women treated with
      an oral bisphosphonate--Danish National Register Based Cohort Study.
AB  - In this Danish national register-based cohort study, we examined the effects of
      alendronate on the development of colon cancers and survival. The incidence of
      colon cancer and mortality rate, once colon cancer had been diagnosed, were lower
      in patients treated with alendronate, posing the question whether alendronate
      acts as chemopreventive. INTRODUCTION: When bisphosphonates are given by mouth,
      around 99% remains non-absorbed in the intestine. Based on their biochemical
      actions, we predicted that oral bisphosphonates might prevent colon cancers.
      METHODS: This is a Danish national register-based cohort study. We identified
      30,606 women aged 50+, mean age 71.9 years, who had not previously taken
      treatments for osteoporosis, who began to take alendronate in 1996-2005, and
      assigned 124,424 individually age- and gender-matched control subjects. The main
      outcome measure was colorectal cancers incidence and post-diagnosis survival in
      patients taking oral alendronate for osteoporosis. RESULTS: Cox proportional
      hazards analysis of death due to colon cancer showed lower risk in alendronate
      users, crude hazard ratio (HR) 0.69 (95% CI 0.59-0.81) with an adjusted HR of
      0.62 (95% CI 0.52-0.72). The reduction in risk comprised both a lower incidence
      of colon cancer-adjusted HR 0.69 (95% CI 0.60-0.79) and a lower mortality once
      colon cancer had been diagnosed, adjusted HR 0.82 (95% CI 0.70-0.97). Weekly
      alendronate was associated with a greater risk reduction than daily alendronate.
      The main findings were unaffected by excluding patients from the analysis who had
      pulmonary disease, a major co-morbid condition in users of alendronate and an
      important cause of death. CONCLUSIONS: The risk of overall deaths from cancer and
      in particular death caused by colon cancer was significantly and substantially
      decreased (40%) in patients treated with alendronate, with survival curves
      deviating progressively after 2 years. Also, the incidence of colon cancer was
      lower in those patients.

PMID- 22392162
TI  - Investigations towards nano-hybrid resin-based composites.
AB  - OBJECTIVE: Clinical data indicate an increased trend in material fracture as
      reason for failure in composite restorations, questioning whether modern resin
      based composites (RBCs) are able to fulfil the rising aesthetical demands and to
      provide at the same time a sufficient mechanical stability also in larger
      cavities. Nano-hybrid RBCs are promoted as materials with improved mechanical
      properties. The aim of this study was to analyse differences in mechanical
      properties within and between modern flowable and non-flowable nano-hybrid and
      micro-hybrid RBCs by measuring mechanical properties at macro- and micro-scale.
      METHODS: Thirty-four RBCs with traditional and new monomer formulation or photo
      polymerization initiator technology-15 nano-hybrid, nine micro-hybrid and ten
      flowable-were therefore considered. Flexural strength, flexural modulus
      (E(flexural)), indentation modulus, Vickers hardness (HV) and creep were measured
      after the samples had been stored in water for 24 h at 37 degrees C. Differences
      within the materials as well as within material categories were statistically
      analysed using one-way ANOVA with Tukey HSD post hoc test (alpha = 0.05) as well
      as partial eta-square statistics. RESULTS: The category of micro- and nano-hybrid
      RBCs performed in all properties superior compared to the flowable RBCs. The
      former two categories differ significantly only with regard to three parameters,
      with nano-hybrid RBCs showing higher HV respectively lower E(flexural) and filler
      weight. The micro-mechanical parameters proved to be more sensitive to
      differences in filler amount and RBCs type than the macro-mechanical properties.
      CLINICAL RELEVANCE: Only few differences were found between nano-hybrid and micro
      hybrid RBCs as a material category and thus, from laboratory tests, no clear
      advantages in the mechanical stability in stress-bearing areas of nano-hybrid
      RBCs are expected clinically. Similar is valid for materials with new monomer
      formulation or photo-polymerization initiator technology. However, several of the
      measured nano-hybrid RBCs showed consistently higher mechanical properties than
      the mean values of the micro-hybrid RBCs.

PMID- 22392163
TI  - Clinical results of lithium-disilicate crowns after up to 9 years of service.
AB  - OBJECTIVES: The purpose of this prospective study was to evaluate the clinical
      outcome of anterior and posterior crowns made of a lithium-disilicate glass
      ceramic framework material (IPS e.max Press, Ivoclar Vivadent). MATERIALS AND
      METHODS: A total of 104 single crowns were placed in 41 patients (mean age, 34 +/
      9.6 years; 15 male, 26 female). Eighty-two anterior and 22 posterior crowns were
      inserted. All teeth received a 1-mm-wide chamfer or rounded shoulder preparation
      with an occlusal/incisal reduction of 1.5-2.0 mm. The minimum framework thickness
      was 0.8 mm. Frameworks were laminated by a prototype of a veneering material
      combined with an experimental glaze. Considering the individual abutment
      preconditions, the examined crowns were either adhesively luted (69.2 %) or
      inserted with glass-ionomer cement (30.8 %). Follow-up appointments were
      performed 6 months after insertion, then annually. Replacement of a restoration
      was defined as failure. RESULTS: Four patients (10 crowns) were defined as
      dropouts. For the remaining 94 crowns, the mean observation time was 79.5 months
      (range, 34-109.7 months). The cumulative survival rate according to Kaplan-Meier
      was 97.4 % after 5 years and 94.8 % after 8 years. Applying log rank test, it was
      shown that the location of the crown did not significantly have an impact on the
      survival rate (p = 0.74) and that the cementation mode did not significantly
      influence the occurrence of complications (p = 0.17). CONCLUSIONS: The
      application of lithium-disilicate framework material for single crowns seems to
      be a reliable treatment option. CLINICAL RELEVANCE: Crowns made of a lithium
      disilicate framework material can be used clinically in the anterior and
      posterior region irrespective of an adhesive or conventional cementation when
      considering abutment preconditions.

PMID- 22392164
TI  - Multidisciplinary outpatient rehabilitation following cardiac revascularization
      or valve surgery: patient-related factors for uptake.
AB  - BACKGROUND: There are concerns in Europe regarding the service provision and
      accessibility of multidisciplinary cardiac rehabilitation (MDCR) in general, and
      particularly in ambulatory settings. This paper analyses the utilization of
      outpatient MDCR and its determinants after cardiac revascularization or valve
      surgery in Belgium. METHODS: Claims rehabilitation data for all patients
      discharged in 2007 after a percutaneous cardiac intervention or cardiac surgery
      were available from the Belgian Common Sickness Funds Agency. Logistic
      regressions were performed to identify patients demographic and socioeconomic
      characteristics associated with the uptake of outpatient MDCR during the year
      following the hospital discharge. RESULTS: A total of 29,021 patients were
      included. During the hospitalization for the cardiac procedure, 44% were offered
      inpatient MDCR. After discharge, only 15.6% followed at least one session of
      outpatient MDCR. The chance of attending outpatient MDCR was lower for female,
      disabled, and older patients, as well as unemployed patients. The absence of an
      authorized MDCR centre in the neighbourhood of the patient's residence decreased
      the chance of attending outpatient MDCR, while living in a neighbourhood with a
      high education and income level increased this probability. CONCLUSION: These
      results confirm the low rates of MDCR attendance found in a previous study
      performed by the European Association of Cardiovascular Prevention and
      Rehabilitation. The study shows specific patient groups that should be targeted
      in priority, i.e. women, elderly, unemployed patients, disabled persons, and
      patients with a low socioeconomic status.

PMID- 22392165
TI  - Advances in clinical application of quantitative myocardial perfusion imaging.

PMID- 22392166
TI  - CME instructions: PET measurement of adenosine stimulated absolute myocardial
      blood flow for physiological assessment of the coronary circulation.

PMID- 22392168
TI  - Analgesic effect of breast milk versus sucrose for analgesia during heel lance in
      late preterm infants.
AB  - OBJECTIVE: The purpose of this trial was to investigate whether breast milk
      (either breastfed or bottle-fed) has a better analgesic effect than sucrose in
      newborns born at a postmenstrual age between 32 and 37 weeks. METHODS: We
      conducted a randomized controlled trial at a secondary care neonatal unit in the
      Netherlands on 71 preterm neonates (postmenstrual age at birth 32-37 weeks),
      undergoing heel lance with an automated piercing device. Newborns were randomly
      assigned to breast milk (either breastfed or bottle-fed) administered during heel
      lance or oral sucrose administered before heel lance. We assessed the Premature
      Infant Pain Profile (PIPP) score (range, 0-21) to investigate whether there was a
      difference in pain score between neonates receiving breast milk and those
      receiving sucrose solution. RESULTS: There was no significant difference in mean
      PIPP score between neonates receiving breast milk (6.1) and those receiving
      sucrose (5.5), with a mean difference of 0.6 (95% confidence interval -1.6 to
      2.8; P = .58). CONCLUSIONS: From this study, it cannot be concluded that breast
      milk has a better analgesic effect than sucrose in late preterm infants. From the
      results, it follows with 95% confidence that the analgesic effect of breast milk
      is not >1.6 points better and not > 2.8 points worse on the PIPP scale (SD 3.7)
      than the analgesic effect of sucrose in late preterm infants.

PMID- 22392169
TI  - Breast milk and glucose for pain relief in preterm infants: a noninferiority
      randomized controlled trial.
AB  - OBJECTIVE: The study goal was to compare the efficacy of expressed breast milk
      (EBM) versus 25% glucose on pain responses of late preterm infants during heel
      lancing. METHODS: In a noninferiority randomized controlled trial, a total of 113
      newborns were randomized to receive EBM (experimental group [EG]) or 25% glucose
      (control group [CG]) before undergoing heel lancing. The primary outcome was pain
      intensity (Premature Infant Pain Profile [PIPP]) and a 10% noninferiority margin
      was established. Secondary outcomes were incidence of cry and percentage of time
      spent crying and adverse events. Intention-to-treat (ITT) analysis was used.
      RESULTS: Groups were similar regarding demographics and clinical characteristics,
      except for birth weight and weight at data collection day. There were lower pain
      scores in the CG over 3 minutes after lancing (P < .001). A higher number of
      infants in the CG had PIPP scores indicative of minimal pain or absence of pain
      (P = .002 and P = .003 on ITT analysis) at 30 seconds after lancing, and the mean
      difference in PIPP scores was 3 (95% confidence interval: 1.507-4.483). Lower
      incidence of cry (P = .001) and shorter duration of crying (P = .014) were
      observed for CG. Adverse events were benign and self-limited, and there was no
      significant difference between groups (P = .736 and P = .637 on ITT analysis).
      CONCLUSIONS: Results based on PIPP scores and crying time indicate poorer effects
      of EBM compared with 25% glucose during heel lancing. Additional studies
      exploring the vol and administration of EBM and its combination with other
      strategies such as skin-to-skin contact and sucking are necessary.

PMID- 22392170
TI  - Nosocomial rotavirus infections: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Nosocomial rotavirus (nRV) infections represent an
      important part of rotavirus (RV)-associated morbidity. The incidence of nRV
      influences the estimated total RV disease burden, an important determinant of
      cost-effectiveness of RV vaccination programs. Our aim is to summarize the
      existing evidence and produce reliable estimates of nRV incidence, in pediatric
      settings in Europe and North America. METHODS: We searched electronic databases
      for studies on nRV incidence among pediatric inpatients. To ascertain complete
      case reporting, only studies describing active nRV surveillance in their
      methodology were included. Random effects meta-analysis was performed. Meta
      regression was used to obtain results adjusted for important study
      characteristics. RESULTS: Twenty surveillance studies met the quality criteria
      for inclusion. The pooled unadjusted nRV incidence was 2.9 per 100
      hospitalizations (95% confidence interval [CI]: 1.6-4.4). Incidence was
      significantly influenced by studies' seasonality-months (RV epidemic season only
      or year-round) and the age range of included patients. Highest nRV incidence was
      found for children <2 years of age, hospitalized during the epidemic months
      (8.1/100 hospitalizations; 95% CI: 6.4-9.9). The adjusted year-round nRV
      incidence estimate without age restriction was 0.4/100 hospitalizations (95% CI:
      0.1-2.1) and 0.7 (95% CI: 0.0-1.8) for children <5 years of age. CONCLUSIONS:
      This is the first meta-analysis to summarize results of surveillance studies on
      nRV incidence. nRV is an important problem among hospitalized infants during the
      winter months. The lower season and age-adjusted nRV incidence estimate seems
      more appropriate for application in population-based burden of disease analysis.

PMID- 22392171
TI  - Neonatal liver cirrhosis without iron overload caused by gestational alloimmune
      liver disease.
AB  - Gestational alloimmune liver disease has emerged as the major cause of antenatal
      liver injury and failure. It usually manifests as neonatal liver failure with
      hepatic and extrahepatic iron overload, a clinical presentation called neonatal
      hemochromatosis. We report on a newborn in whom fetal hepatomegaly was detected
      during pregnancy and who presented at birth with liver cirrhosis and mild liver
      dysfunction. Liver biopsy showed the absence of iron overload but strong
      immunostaining of hepatocytes for the C5b-9 complex, the terminal complement
      cascade neoantigen occurring specifically during complement activation by the
      immunoglobulin G-mediated classic pathway, which established the alloimmune
      nature of the hepatocyte injury. The infant survived with no specific therapy,
      and follow-up until 36 months showed progressive normalization of all liver
      parameters. This case report expands the recognized clinical spectrum of
      congenital alloimmune liver disease to include neonatal liver disease and
      cirrhosis, even in the absence of siderosis. Such a diagnosis is of utmost
      importance regarding the necessity for immunotherapy in further pregnancies to
      avoid recurrence of alloimmune injury.

PMID- 22392172
TI  - Clinic-integrated behavioral intervention for families of youth with type 1
      diabetes: randomized clinical trial.
AB  - OBJECTIVE: To test the effect on diabetes management outcomes of a low-intensity,
      clinic-integrated behavioral intervention for families of youth with type 1
      diabetes. METHODS: Families (n = 390) obtaining care for type 1 diabetes
      participated in a 2-year randomized clinical trial of a clinic-integrated
      behavioral intervention designed to improve family diabetes management practices.
      Measurement of hemoglobin A1c, the primary outcome, was obtained at each clinic
      visit and analyzed centrally. Blood glucose meter data were downloaded at each
      visit. Adherence was assessed by using a semistructured interview at baseline,
      mid-study, and follow-up. Analyses included 2-sample t tests at predefined time
      intervals and mixed-effect linear-quadratic models to assess for difference in
      change in outcomes across the study duration. RESULTS: A significant overall
      intervention effect on change in glycemic control from baseline was observed at
      the 24-month interval (P = .03). The mixed-effect model showed a significant
      intervention by age interaction (P < .001). Among participants aged 12 to 14, a
      significant effect on glycemic control was observed (P = .009 for change from
      baseline to 24-month interval; P = .035 for mixed-effect model across study
      duration), but there was no effect among those aged 9 to 11. There was no
      intervention effect on child or parent report of adherence; however, associations
      of change in adherence with change in glycemic control were weak. CONCLUSIONS:
      This clinic-integrated behavioral intervention was effective in preventing the
      deterioration in glycemic control evident during adolescence, offering a
      potential model for integrating medical and behavioral sciences in clinical care.

PMID- 22392173
TI  - Interrater reliability of clinical findings in children with possible
      appendicitis.
AB  - OBJECTIVE: Our objective was to determine the interrater reliability of clinical
      history and physical examination findings in children undergoing evaluation for
      possible appendicitis in a large, multicenter cohort. METHODS: We conducted a
      prospective, multicenter, cross-sectional study of children aged 3-18 years with
      possible appendicitis. Two clinicians independently evaluated patients and
      completed structured case report forms within 60 minutes of each other and
      without knowing the results of diagnostic imaging. We calculated raw agreement
      and assessed reliability by using the unweighted Cohen kappa statistic with 2
      sided 95% confidence intervals. RESULTS: A total of 811 patients had 2
      assessments completed, and 599 (74%) had 2 assessments completed within 60
      minutes. Seventy-five percent of paired assessments were completed by pediatric
      emergency physicians. Raw agreement ranged from 64.9% to 92.3% for history
      variables and 4 of 6 variables had moderate interrater reliability (kappa > .4).
      The highest kappa values were noted for duration of pain (kappa = .56 [95%
      confidence intervals .51-.61]) and history of emesis (.84 [.80-.89]). For
      physical examination variables, raw agreement ranged from 60.9% to 98.7%, with 4
      of 8 variables exhibiting moderate reliability. Among physical examination
      variables, the highest kappa values were noted for abdominal pain with walking,
      jumping, or coughing (.54 [.45-.63]) and presence of any abdominal tenderness on
      examination (.49 [.19-.80]). CONCLUSIONS: Interrater reliability of patient
      history and physical examination variables was generally fair to moderate. Those
      variables with higher interrater reliability are more appropriate for inclusion
      in clinical prediction rules in children with possible appendicitis.

PMID- 22392175
TI  - Pediatric office pain: crying for attention.

PMID- 22392174
TI  - Alcohol consumption in movies and adolescent binge drinking in 6 European
      countries.
AB  - OBJECTIVE: The goal of this study was to investigate whether the association
      between exposure to images of alcohol use in movies and binge drinking among
      adolescents is independent of cultural context. METHODS: A cross-sectional survey
      study in 6 European countries (Germany, Iceland, Italy, Netherlands, Poland, and
      Scotland) was conducted. A total of 16 551 pupils from 114 public schools with a
      mean (+/- SD) age of 13.4 (+/- 1.18) years participated. By using previously
      validated methods, exposure to alcohol use in movies was estimated from the 250
      top-grossing movies of each country (years 2004-2009). Lifetime binge drinking
      was the main outcome measure. RESULTS: Overall, 27% of the sample had consumed >5
      drinks on at least 1 occasion in their life. After controlling for age, gender,
      family affluence, school performance, television screen time, sensation seeking
      and rebelliousness, and frequency of drinking of peers, parents, and siblings,
      the adjusted beta-coefficient for lifetime binge drinking in the entire sample
      was 0.12 (95% confidence interval: 0.10-0.14; P < .001). The crude relationship
      between movie alcohol use exposure and lifetime binge drinking was significant in
      all countries; after covariate adjustment, the relationship was still significant
      in 5 of 6 countries. A sensitivity analysis revealed that the association is
      content specific, as there was no significant association between lifetime binge
      drinking and exposure to smoking in movies. CONCLUSIONS: The link between alcohol
      use in movies and adolescent binge drinking was robust and seems relatively
      unaffected by cultural contexts.

PMID- 22392176
TI  - Utilizing improvement science methods to improve physician compliance with proper
      hand hygiene.
AB  - OBJECTIVE: In 2009, The Joint Commission challenged hospitals to reduce the risk
      of health care-associated infections through hand hygiene compliance. At our
      hospital, physicians had lower compliance rates than other health care workers,
      just 68% on general pediatric units. We used improvement methods and reliability
      science to increase compliance with proper hand hygiene to >95% by inpatient
      general pediatric teams. METHODS: Strategies to improve hand hygiene were tested
      through multiple plan-do-study-act cycles, first by 1 general inpatient medical
      team and then spread to 4 additional teams. At the start of each rotation,
      residents completed an educational module and posttest about proper hand hygiene.
      Team compliance data were displayed daily in the resident conference room. Real
      time identification and mitigation of failures by a hand-washing champion
      encouraged shared accountability. Organizational support ensured access to
      adequate hand hygiene supplies. The main outcome measure was percent compliance
      with acceptable hand hygiene, defined as use of an alcohol-based product or hand
      washing with soap and turning off the faucet without using fingers or palm.
      Compliance was defined as acceptable hand hygiene before and after contact with
      the patient or care environment. Covert bedside observers recorded at least 8
      observations of physicians' compliance per day. RESULTS: Physician compliance
      with proper hand hygiene improved to >95% within 6 months and was sustained for
      11 months. CONCLUSIONS: Instituting a hand-washing champion for immediate
      identification and mitigation of failures was key in sustaining results.
      Improving physician compliance with proper hand hygiene is achievable and a first
      step in decreasing health care-associated infections.

PMID- 22392177
TI  - Barriers to conducting advance care discussions for children with life
      threatening conditions.
AB  - BACKGROUND AND OBJECTIVE: Advance care discussions (ACD) occur infrequently or
      are initiated late in the course of illness. Although data exist regarding
      barriers to ACD among the care of adult patients, few pediatric data exist. The
      goal of this study was to identify barriers to conducting ACD for children with
      life-threatening conditions. METHODS: Physicians and nurses from practice
      settings where advance care planning typically takes place were surveyed to
      collect data regarding their attitudes and behaviors regarding ACD. RESULTS: A
      total of 266 providers responded to the survey: 107 physicians and 159 nurses
      (54% response rate). The top 3 barriers were: unrealistic parent expectations,
      differences between clinician and patient/parent understanding of prognosis, and
      lack of parent readiness to have the discussion. Nurses identified lack of
      importance to clinicians (P = .006) and ethical considerations (P < .001) as
      impediments more often than physicians. Conversely, physicians believed that not
      knowing the right thing to say (P = .006) was more often a barrier. There are
      also perceived differences among specialties. Cardiac ICU providers were more
      likely to report unrealistic clinician expectations (P < .001) and differences
      between clinician and patient/parent understanding of prognosis (P = .014) as
      common barriers to conducting ACD. Finally, 71% of all clinicians believed that
      ACD happen too late in the patient's clinical course. CONCLUSIONS: Clinicians
      perceive parent prognostic understanding and attitudes as the most common
      barriers to conducting ACD. Educational interventions aimed at improving
      clinician knowledge, attitudes, and skills in addressing these barriers may help
      health care providers overcome perceived barriers.

PMID- 22392178
TI  - A Saudi family making end-of-life decisions in the PICU.

PMID- 22392179
TI  - A randomized controlled trial of zinc as adjuvant therapy for severe pneumonia in
      young children.
AB  - BACKGROUND AND OBJECTIVE: Diarrhea and pneumonia are the leading causes of
      illness and death in children <5 years of age. Zinc supplementation is effective
      for treatment of acute diarrhea and can prevent pneumonia. In this trial, we
      measured the efficacy of zinc when given to children hospitalized and treated
      with antibiotics for severe pneumonia. METHODS: We enrolled 610 children aged 2
      to 35 months who presented with severe pneumonia defined by the World Health
      Organization as cough and/or difficult breathing combined with lower chest
      indrawing. All children received standard antibiotic treatment and were
      randomized to receive zinc (10 mg in 2- to 11-month-olds and 20 mg in older
      children) or placebo daily for up to 14 days. The primary outcome was time to
      cessation of severe pneumonia. RESULTS: Zinc recipients recovered marginally
      faster, but this difference was not statistically significant (hazard ratio =
      1.10, 95% CI 0.94-1.30). Similarly, the risk of treatment failure was slightly
      but not significantly lower in those who received zinc (risk ratio = 0.88 95% CI
      0.71-1.10). CONCLUSIONS: Adjunct treatment with zinc reduced the time to
      cessation of severe pneumonia and the risk of treatment failure only marginally,
      if at all, in hospitalized children.

PMID- 22392180
TI  - Blue rubber bleb nevus syndrome: successful treatment with sirolimus.
AB  - Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder with characteristic
      vascular malformations of the skin, gastrointestinal system, and, less often,
      other organ systems. The characteristic cutaneous lesions consist of deep-blue,
      soft, rubbery blebs, which are easily compressible. The most serious complication
      is abundant gastrointestinal bleeding. We describe the case of an 8-year-old girl
      with diagnosed BRBNS who had multiple venous malformations all over her body,
      importantly, throughout the gastrointestinal tract, mouth, esophagus, stomach,
      small bowel, and colon. She presented with recurrent massive gastrointestinal
      bleeding and soft tissue hematoma despite prednisolone and alpha-interferon
      therapy. We started low-dose sirolimus as an antiangiogenic agent. The vascular
      masses were reduced rapidly and there was no gastrointestinal bleeding and
      muscular hematoma after sirolimus therapy. There was no drug adverse reaction at
      20-month follow-up. To the best of our knowledge, this is the first report
      related to the use of sirolimus in a patient with BRBNS.

PMID- 22392182
TI  - Development of a pragmatic measure for evaluating and optimizing rapid response
      systems.
AB  - OBJECTIVES: Standard metrics for evaluating rapid response systems (RRSs) include
      cardiac and respiratory arrest rates. These events are rare in children;
      therefore, years of data are needed to evaluate the impact of RRSs with
      sufficient statistical power. We aimed to develop a valid, pragmatic measure for
      evaluating and optimizing RRSs over shorter periods of time. METHODS: We reviewed
      724 medical emergency team and 56 code-blue team activations in a children's
      hospital between February 2010 and February 2011. We defined events resulting in
      ICU transfer and noninvasive ventilation, intubation, or vasopressor infusion
      within 12 hours as "critical deterioration." By using in-hospital mortality as
      the gold standard, we evaluated the test characteristics and validity of this
      proximate outcome metric compared with a national benchmark for cardiac and
      respiratory arrest rates, the Child Health Corporation of America Codes Outside
      the ICU Whole System Measure. RESULTS: Critical deterioration (1.52 per 1000 non
      ICU patient-days) was more than eightfold more common than the Child Health
      Corporation of America measure of cardiac and respiratory arrests (0.18 per 1000
      non-ICU patient-days) and was associated with >13-fold increased risk of in
      hospital death. The critical deterioration metric demonstrated both criterion and
      construct validity. CONCLUSIONS: The critical deterioration rate is a valid,
      pragmatic proximate outcome associated with in-hospital mortality. It has great
      potential for complementing existing patient safety measures for evaluating RRS
      performance.

PMID- 22392181
TI  - Sleep-disordered breathing in a population-based cohort: behavioral outcomes at 4
      and 7 years.
AB  - OBJECTIVES: Examine statistical effects of sleep-disordered breathing (SDB)
      symptom trajectories from 6 months to 7 years on subsequent behavior. METHODS:
      Parents in the Avon Longitudinal Study of Parents and Children reported on
      children's snoring, mouth breathing, and witnessed apnea at >=2 surveys at 6, 18,
      30, 42, 57, and 69 months, and completed the Strengths and Difficulties
      Questionnaire at 4 (n = 9140) and 7 (n = 8098) years. Cluster analysis produced 5
      "Early" (6-42 months) and "Later" (6-69 months) symptom trajectories
      ("clusters"). Adverse behavioral outcomes were defined by top 10th percentiles on
      Strengths and Difficulties Questionnaire total and subscales, at 4 and 7 years,
      in multivariable logistic regression models. RESULTS: The SDB clusters predicted
      ~20% to 100% increased odds of problematic behavior, controlling for 15 potential
      confounders. Early trajectories predicted problematic behavior at 7 years equally
      well as at 4 years. In Later trajectories, the "Worst Case" cluster, with peak
      symptoms at 30 months that abated thereafter, nonetheless at 7 years predicted
      hyperactivity (1.85 [1.30-2.63]), and conduct (1.60 [1.18-2.16]) and peer
      difficulties (1.37 [1.04-1.80]), whereas a "Later Symptom" cluster predicted
      emotional difficulties (1.65 [1.21-2.07]) and hyperactivity (1.88 [1.42-2.49]) .
      The 2 clusters with peak symptoms before 18 months that resolve thereafter still
      predicted 40% to 50% increased odds of behavior problems at 7 years. CONCLUSIONS:
      In this large, population-based, longitudinal study, early-life SDB symptoms had
      strong, persistent statistical effects on subsequent behavior in childhood.
      Findings suggest that SDB symptoms may require attention as early as the first
      year of life.

PMID- 22392183
TI  - Electrocardiogram screening for disorders that cause sudden cardiac death in
      asymptomatic children: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Pediatric sudden cardiac death (SCD) occurs in an
      estimated 0.8 to 6.2 per 100 000 children annually. Screening for cardiac
      disorders causing SCD in asymptomatic children has public appeal because of its
      apparent potential to avert tragedy; however, performance of the
      electrocardiogram (ECG) as a screening tool is unknown. We estimated (1)
      phenotypic (ECG- or echocardiogram [ECHO]-based) prevalence of selected pediatric
      disorders associated with SCD, and (2) sensitivity, specificity, and predictive
      value of ECG, alone or with ECHO. METHODS: We systematically reviewed literature
      on hypertrophic cardiomyopathy (HCM), long QT syndrome (LQTS), and Wolff
      Parkinson-White syndrome, the 3 most common disorders associated with SCD and
      detectable by ECG. RESULTS: We identified and screened 6954 abstracts, yielding
      396 articles, and extracted data from 30. Summary phenotypic prevalences per 100
      000 asymptomatic children were 45 (95% confidence interval [CI]: 10-79) for HCM,
      7 (95% CI: 0-14) for LQTS, and 136 (95% CI: 55-218) for Wolff-Parkinson-White.
      The areas under the receiver operating characteristic curves for ECG were 0.91
      for detecting HCM and 0.92 for LQTS. The negative predictive value of detecting
      either HCM or LQTS by using ECG was high; however, the positive predictive value
      varied by different sensitivity and specificity cut-points and the true
      prevalence of the conditions. CONCLUSIONS: Results provide an evidence base for
      evaluating pediatric screening for these disorders. ECG, alone or with ECHO, was
      a sensitive test for mass screening and negative predictive value was high, but
      positive predictive value and false-positive rates varied.

PMID- 22392184
TI  - Interplay between SAFE and RISK pathways in sphingosine-1-phosphate-induced
      cardioprotection.
AB  - PURPOSE: We studied the role of two powerful molecular signalling mechanisms
      involved in the cardioprotective effect of sphingosine-1-phosphate (S1P), a major
      component of high density lipoprotein (HDL) against myocardial ischaemic
      reperfusion injury, namely the RISK pathway (Akt/Erk), including its downstream
      target FOXO-1 and, the SAFE pathway (TNF/STAT-3). METHODS: Control hearts from
      wildtype, TNF deficient (TNF(-/-)) or cardiomyocyte STAT-3 deficient (STAT-3(-/
      )) male mice were perfused on a Langendorff apparatus (35 min global ischaemia
      and 45 min reperfusion). S1P (10 nM) was given at the onset of reperfusion for
      the first 7 min, with/without STAT-3 or Akt inhibitors, AG490 and wortmannin (W),
      respectively. RESULTS: S1P reduced myocardial infarct size in wildtype hearts
      (39.3+/-4.4% in control vs 17.3+/-3.1% in S1P-treated hearts; n>=6; p<0.05) but
      not in STAT-3(-/-) or TNF(-/-) mice (34.2+/-4.3% in STAT-3(-/-) and 34.1+/-2.0%
      in TNF(-/-) mice; n>=6; p=ns vs. their respective control). Both STAT-3 and Akt
      inhibitors abolished the protective effects of S1P (33.7+/-3.3% in S1P + AG490
      and 36.6+/-4.9% in S1P + W; n=6; p=ns vs. their respective control). Increased
      nuclear levels of phosphorylated STAT-3 (pSTAT-3), Akt and FOXO-1 were observed
      at 15 min reperfusion in wildtype mice with Western Blot analysis (53% STAT-3,
      47% Akt, 41% FOXO-1; p<0.05 vs control) but not in STAT-3-/- mice or in wiltype
      hearts treated with the Akt inhibitor. Interestingly, an activation of pSTAT-3
      was noticed in the mitochondria at 7 min but not 15 min of reperfusion.
      CONCLUSIONS: In conclusion, S1P activates both the SAFE and RISK pathways,
      therefore suggesting a dual protective signalling in S1P-induced
      cardioprotection.

PMID- 22392185
TI  - Renin inhibitors and cardiovascular and renal protection: an endless quest?
AB  - Renin-angiotensin system (RAS) blockade with angiotensin-converting enzyme (ACE)
      inhibitors or angiotensin receptor blockers (ARBs) has become a major therapeutic
      approach in medicine since the end of the 1970's. Although these molecules were
      the first RAS blockers to be developed, it would have been physiologically and
      pharmacologically more pertinent to selectively inhibit renin itself. Indeed, the
      reaction between renin and its unique substrate, angiotensinogen, is the highly
      regulated and rate-limiting step of the RAS. The development of direct renin
      inhibitors (DRI) has been a slow and complex process and the synthesis of the
      first orally active DRI, aliskiren, was only achieved in the 2000's. Its
      pharmacological profile in patients with hypertension, diabetic nephropathy or
      heart failure, in addition to experimental evidence, suggests that aliskiren may
      be of value for the management of cardiovascular and renal diseases. However, the
      long-term, randomized, placebo-controlled, morbidity/mortality trial, ALTITUDE,
      which included 8,600 patients with type 2 diabetes, proteinuria and a high
      cardiovascular risk already treated with ACE inhibitors or ARBs was terminated in
      December 2011 because of futility and an increased incidence of serious adverse
      events in the aliskiren 300 mg arm. Other long-term studies are still ongoing to
      demonstrate the safety and efficacy of aliskiren to reduce cardiovascular
      morbidity and mortality in patients with heart failure and in elderly individuals
      (>=65 years) with systolic blood pressure of 130 to 159 mmHg, no overt
      cardiovascular disease, and a high cardiovascular risk profile. In the meantime,
      according to the European Medicines Agency recommendations, aliskiren should not
      be prescribed to diabetic patients in combination with ACE inhibitors or ARBs.

PMID- 22392186
TI  - Obesity, inflammation and brachial artery flow-mediated dilatation: therapeutic
      targets in patients with microvascular angina (cardiac syndrome X).
AB  - BACKGROUND: The pathophysiology of microvascular angina (cardiac syndrome X,
      CSX), (effort-induced angina, a positive response to exercise stress testing and
      angiographically normal coronary arteries) has not been fully elucidated. Various
      pathogenic mechanisms have been proposed, amongst which coronary microvascular
      dysfunction features prominently. Management of patients with microvascular
      angina is often challenging as a substantial number of patients does not respond
      to conventional anti-anginal therapy. In this study, we sought to assess the
      association between brachial artery FMD, high-sensitive C-reactive protein (hs
      CRP) and cardiovascular risk factors including obesity in patients with cardiac
      syndrome X. METHODS AND RESULTS: Thirty-four consecutive CSX patients (29 female,
      mean age 60 +/- 9 years) were recruited from a specialised CSX clinic. Twelve
      asymptomatic subjects (10 female, mean age 51 +/- 12 years) with comparable
      cardiovascular risk factor profile served as controls. All participants underwent
      standardized computer-assisted FMD measurements and assessment of hs-CRP
      concentrations at study entry. Body mass index (BMI), used as a general measure
      of obesity was calculated as weight (kilograms) divided by height (meters
      squared). Compared to controls, CSX patients had significantly higher hs-CRP
      concentrations (p = 0.003) and impaired FMD (p < 0.01). Moreover, among the CSX
      patients, a correlation between FMD and hs-CRP (r = -0.66, p < 0.01), FMD and BMI
      (r = 0.377, p = 0.028), and hs-CRP and BMI (r = -0.372, p = 0.030) was found.
      CONCLUSION: Impaired brachial artery FMD is significantly associated with
      elevated hs-CRP concentrations and BMI in patients with CSX. The results support
      the concept that low-grade inflammation and obesity may promote vascular
      dysfunction in these patients representing therapeutic targets for future
      research investigations.

PMID- 22392187
TI  - Animal models of prenatal immune challenge and their contribution to the study of
      schizophrenia: a systematic review.
AB  - Prenatal immune challenge (PIC) in pregnant rodents produces offspring with
      abnormalities in behavior, histology, and gene expression that are reminiscent of
      schizophrenia and autism. Based on this, the goal of this article was to review
      the main contributions of PIC models, especially the one using the viral-mimetic
      particle polyriboinosinic-polyribocytidylic acid (poly-I:C), to the understanding
      of the etiology, biological basis and treatment of schizophrenia. This systematic
      review consisted of a search of available web databases (PubMed, SciELO, LILACS,
      PsycINFO, and ISI Web of Knowledge) for original studies published in the last 10
      years (May 2001 to October 2011) concerning animal models of PIC, focusing on
      those using poly-I:C. The results showed that the PIC model with poly-I:C is able
      to mimic the prodrome and both the positive and negative/cognitive dimensions of
      schizophrenia, depending on the specific gestation time window of the immune
      challenge. The model resembles the neurobiology and etiology of schizophrenia and
      has good predictive value. In conclusion, this model is a robust tool for the
      identification of novel molecular targets during prenatal life, adolescence and
      adulthood that might contribute to the development of preventive and/or treatment
      strategies (targeting specific symptoms, i.e., positive or negative/cognitive)
      for this devastating mental disorder, also presenting biosafety as compared to
      viral infection models. One limitation of this model is the incapacity to model
      the full spectrum of immune responses normally induced by viral exposure.

PMID- 22392188
TI  - Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and
      anxiety.
AB  - Electrical stimulation of midbrain tectum structures, particularly the dorsal
      periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive
      responses, such as freezing and escape behavior. Freezing also ensues after
      termination of dPAG stimulation (post-stimulation freezing). These defensive
      reaction responses are critically mediated by gamma-aminobutyric acid and 5
      hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play
      a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are
      involved in the global processing and expression of fear at the level of the
      midbrain tectum is yet unclear. The present study investigated the role of NK-1
      receptors in unconditioned defensive behavior induced by electrical stimulation
      of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 MUL), a selective
      NK-1 antagonist, injected into these midbrain structures had anti-aversive
      effects on defensive responses and distress ultrasonic vocalizations induced by
      stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of
      spantide did not influence post-stimulation freezing or alter exploratory
      behavior in rats subjected to the elevated plus maze. These results suggest that
      NK-1 receptors are mainly involved in the mediation of defensive behavior
      organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation
      freezing was not affected by intra-dPAG injections of spantide, suggesting that
      NK-1-mediated mechanisms are only involved in the output mechanisms of defensive
      behavior and not involved in the processing of ascending aversive information
      from the dPAG.

PMID- 22392191
TI  - Highlights of novel melanoma therapies presented at the 8th International
      Congress of the Society for Melanoma Research (SMR) Tampa, FL, November 9-11,
      2011.

PMID- 22392190
TI  - Induction on differentiation and modulation of bone marrow progenitor of
      dendritic cell by methionine enkephalin (MENK).
AB  - Methionine enkephalin (MENK), the endogenous neuropeptide, is known to exert
      direct effects on the neuroendocrine and the immune systems and participates in
      regulation of various functions of cells related to both the innate and adaptive
      immune systems. Dendritic cells (DCs) play important role in initiating and
      regulating T cell responses. The aim of this work is to investigate the effects
      of MENK on differentiation, maturation, and function of DCs derived from murine
      bone marrow progenitors (BM-derived DCs). Our result showed that MENK could
      induce BM-derived DCs to polarize predominantly to mDC subtype, rather than pDC
      both in vivo and in vitro, and this was in favor of Th1 response. BM-derived DCs,
      after treatment with MENK, up-regulated the expressions of MHC class II and key
      costimulatory molecules. Result by RT-PCR showed MENK could increase expressions
      of delta and kappa receptors on BM-derived DCs. Also MENK promoted BM-derived DCs
      to secret higher levels of proinflammatory cytokines of IL-12p70, TNF-alpha.
      Furthermore, differentiated BM-derived DCs treated with MENK displayed higher
      activity to induce allogeneic T cell proliferation and MENK also inhibited tumor
      growth in vivo and induced apoptosis of tumor cells in vitro. Thus, it is
      concluded that MENK could be an effective inducer of BM-derived DCs and might be
      a new therapeutic agent for cancer, as well as other immune handicapped disease.
      Also we may consider MENK as a potential adjuvant in vaccine preparation.

PMID- 22392189
TI  - Fine-tuning of defensive behaviors in the dorsal periaqueductal gray by atypical
      neurotransmitters.
AB  - This paper presents an up-to-date review of the evidence indicating that atypical
      neurotransmitters such as nitric oxide (NO) and endocannabinoids (eCBs) play an
      important role in the regulation of aversive responses in the periaqueductal gray
      (PAG). Among the results supporting this role, several studies have shown that
      inhibitors of neuronal NO synthase or cannabinoid receptor type 1 (CB1) receptor
      agonists cause clear anxiolytic responses when injected into this region. The
      nitrergic and eCB systems can regulate the activity of classical
      neurotransmitters such as glutamate and gamma-aminobutyric acid (GABA) that
      control PAG activity. We propose that they exert a 'fine-tuning' regulatory
      control of defensive responses in this area. This control, however, is probably
      complex, which may explain the usually bell-shaped dose-response curves observed
      with drugs that act on NO- or CB1-mediated neurotransmission. Even if the
      mechanisms responsible for this complex interaction are still poorly understood,
      they are beginning to be recognized. For example, activation of transient
      receptor potential vanilloid type-1 channel (TRPV1) receptors by anandamide seems
      to counteract the anxiolytic effects induced by CB1 receptor activation caused by
      this compound. Further studies, however, are needed to identify other mechanisms
      responsible for this fine-tuning effect.

PMID- 22392192
TI  - Tumor-associated myeloid cells can be activated in vitro and in vivo to mediate
      antitumor effects.
AB  - Tumor growth is often accompanied by the accumulation of myeloid cells in the
      tumors and lymphoid organs. These cells can suppress T cell immunity, thereby
      posing an obstacle to T cell-targeted cancer immunotherapy. In this study, we
      tested the possibility of activating tumor-associated myeloid cells to mediate
      antitumor effects. Using the peritoneal model of B16 melanoma, we show that
      peritoneal cells (PEC) in tumor-bearing mice (TBM) had reduced ability to secrete
      nitric oxide (NO) following in vitro stimulation with interferon gamma and
      lipopolysaccharide, as compared to PEC from control mice. This reduced function
      of PEC was accompanied by the influx of CD11b(+) Gr-1(+) myeloid cells to the
      peritoneal cavity. Nonadherent PEC were responsible for most of the NO production
      in TBM, whereas in naive mice NO was mainly secreted by adherent CD11b(+)
      F4/80(+) macrophages. Sorted CD11b(+) Gr-1(-) monocytic and CD11b(+) Gr-1(+)
      granulocytic PEC from TBM had a reduced ability to secrete NO following in vitro
      stimulation (compared to naive PEC), but effectively suppressed proliferation of
      tumor cells in vitro. In vivo, treatment of mice bearing established peritoneal
      B16 tumors with anti-CD40 and CpG resulted in activation of tumor-associated PEC,
      reduction in local tumor burden and prolongation of mouse survival. Inhibition of
      NO did not abrogate the antitumor effects of stimulated myeloid cells. Taken
      together, the results indicate that in tumor-bearing hosts, tumor-associated
      myeloid cells can be activated to mediate antitumor effects.

PMID- 22392193
TI  - Factors of empowerment for women in recovery from substance use.
AB  - Empowerment is an interdisciplinary construct heavily grounded in the theories of
      community psychology. Although empowerment has a strong theoretical foundation,
      few context-specific quantitative measures have been designed to evaluate
      empowerment for specific populations. The present study explored the factor
      structure of a modified empowerment scale with a cross-sectional sample of 296
      women in recovery from substance use who lived in recovery homes located
      throughout the United States. Results from an exploratory factor analysis
      identified three factors of psychological empowerment which were closely related
      to previous conceptualizations of psychological empowerment: self-perception,
      resource knowledge and participation. Further analyses demonstrated a
      hierarchical relationship among the three factors, with resource knowledge
      predicting participation when controlling for self-perception. Finally, a
      correlational analysis demonstrated the initial construct validity of each
      factor, as each factor of empowerment was significantly and positively related to
      self-esteem. Implications for the application of psychological empowerment theory
      and research are discussed.

PMID- 22392194
TI  - Highly crystalline strontium ferrites SrFeO(3-delta): an easy and effective wet
      chemistry synthesis.
AB  - The synthesis of strontium ferrite SrFeO(3-delta) has been explored through wet
      chemistry methods in order to optimize a quick, easy and reproducible method to
      obtain the perovskite in pure crystalline form with a high yield. Among the three
      investigated synthetic paths, (i) coprecipitation of hydroxides, (ii)
      coprecipitation of oxalates and (iii) polyol-assisted coprecipitation, only the
      second one was effective in obtaining the desired perovskite modification as a
      single phase. The products were analyzed by means of powder X-ray diffraction
      (XRD) and X-ray photoelectron spectroscopy (XPS), to determine the crystalline
      structure and the chemical composition of the sample surface, respectively, and
      to optimise the synthetic process. Pure samples were further characterised by
      means of inductively coupled plasma (ICP-AES) analysis, nitrogen adsorption,
      elemental analysis, temperature programmed reduction (TPR) and Mossbauer
      spectroscopy.

PMID- 22392195
TI  - Covered stents versus uncovered stents for the palliation of malignant
      extrahepatic biliary obstruction caused by direct tumor invasion: a cohort
      comparative study.
AB  - Biliary stenting is a well-established palliative treatment in patients with
      unresectable malignant biliary strictures. The aim of the present study was to
      compare clinical outcomes of covered and uncovered stents in patients with
      malignant extrahepatic biliary obstruction caused by direct tumor invasion.
      Patients diagnosed with malignant extrahepatic biliary obstruction caused by
      direct tumor invasion were enrolled in this study. Of these patients, 37 received
      ePTFE-covered stent placement and were prospectively studied, and 47 received
      uncovered stent placement and were retrospectively studied. The technical success
      rate, tumor ingrowth rate, complication rate, stent patency, and patient survival
      were evaluated for both groups. Stent placement was successful in all cases
      except one in the covered group due to stent kinking. Tumor ingrowth occurred
      exclusively in the uncovered group. No significant differences were observed for
      the complication rate and patient survival between the two groups. Three patients
      in the covered group experienced stent migration, whereas no patients did in the
      uncovered group. A significant difference was found regarding stent patency,
      which was greater for the covered group compared to the uncovered group. The
      placement of ePTFE-covered stents for the treatment of malignant biliary
      obstruction caused by direct tumor invasion was a safe and an effective method
      characterized by greater stent patency.

PMID- 22392196
TI  - Increased efficacy of a dose-dense regimen of neoadjuvant chemotherapy in breast
      carcinoma: a retrospective analysis.
AB  - Neoadjuvant chemotherapy is being increasingly used in the treatment of breast
      carcinoma. We performed a single-center retrospective analysis of the results of
      neoadjuvant therapy in 376 breast carcinoma patients treated with three different
      regimens combining doxorubicin and paclitaxel (AT), dose-dense doxorubicin and
      cyclophosphamide with sequential weekly paclitaxel (DD AC-P), or the combination
      of trastuzumab with chemotherapy (DD AC-PT). The expression of estrogen receptors
      (ER), progesterone receptors (PR) and human epidermal growth factor receptor
      (HER)-2 was determined immunohistochemically. Pathological response was
      determined in 318 patients. Pathological complete response (pCR) was observed in
      18% of patients. The pCR rate was significantly higher in patients treated with
      DD regimen (22 vs. 13%) and younger than 55 years (23 vs. 13%). The pCR rate was
      higher in patients with triple negative (TN) tumors (43%) and tumors over
      expressing HER-2 (HER-2+; 28%) compared to patients with ER- or PR-positive
      tumors not expressing HER-2 (ER/PR+HER-2-; 6%). In patients with TN tumors pCR
      rate was significantly higher after treatment with DD AC-P compared to AT (61 vs.
      22%, p=0.005). pCR was associated with significantly improved relapse-free
      survival (RFS) and overall survival (OS), but when analysis was performed based
      on tumor phenotype, the difference was significant only in patients with TN
      tumors. In multivariate analysis, pCR, stage, and ER expression were significant
      predictors of RFS, while pCR, stage, ER and DD regimen were significant
      predictors of OS. In conclusion, present data indicate superiority of a DD
      regimen in obtaining pCR in patients with breast carcinoma treated with
      neoadjuvant chemotherapy. The difference in efficacy is due mostly to markedly
      higher pCR rate in patients with TN tumors.

PMID- 22392197
TI  - Sequential FOLFOX-6 and gemcitabine for locally advanced and/or metastatic
      pancreatic cancer.
AB  - This prospective phase II trial aims to evaluate the sequential FOLFOX-6 and
      gemcitabine followed by adapted maintenance for advanced pancreatic cancer.
      Treatment included FOLFOX-6 for 4 cycles, followed sequentially by gemcitabine
      for 3 cycles. Patients, who show clinical benefit after both sequences, will
      receive maintenance treatment based on the investigator's discretion. From
      January 2005 to June 2008, 32 patients with median age of 63 were included; 75%
      of patients had metastatic disease, 81% had pure adenocarcinoma, while 19% had
      adenocarcinoma with a neuroendocrine component. There were 22% PR and 22% SD
      resulting in 44% tumor growth control. Under FOLFOX, grade 3/4 toxicities were
      neutropenia in 8 patients, thrombocytopenia and anemia in 3 patients each, and
      diarrhea in 2 patients. Under Gem, grade 3/4 neutropenia was observed in 4
      patients, thrombocytopenia and anemia were observed in 2 patients, and hand-foot
      syndrome was observed in 3 patients. The median TTP and OS were 4 and 10 months,
      respectively. In APC, FOLFOX-6 regimen followed by gemcitabine achieved an
      interesting RR within a tolerable level of toxicity. This regimen seems to
      warrant further investigation to confirm its efficacy.

PMID- 22392198
TI  - Primary mantle cell lymphoma of the trachea.
AB  - Primary mantle cell lymphoma (MCL) is a controversial entity. It is difficult to
      diagnose MCL in a single organ without lymph node involvement. However, with the
      advent of PET-CT scans and large panels of immunohistochemistry markers, there
      have been increasing reports of primary MCL detected in various organs of which
      the GI tract is the most common. In this case report, we describe the diagnosis
      and clinical course of a patient who presented with "B symptoms" and respiratory
      distress. On further investigation, he was found to have a mass in his trachea,
      which was diagnosed as primary MCL.

PMID- 22392199
TI  - Rare pulmonary primitive neuroectodermal tumor metastasizing to the right atrium:
      a case report.
AB  - A 28-year-old man complained of intermittent irritable dry cough for 2 months
      with occasional bloody sputum. Positron emission tomography-computed tomography
      (PET-CT) suggested multiple heterogeneous soft tissue masses in the inferior
      lobes of both lungs, with heterogeneous increases in 18F-FDG uptake. No metabolic
      disorders were found in the rest of the body. CT-guided percutaneous lung
      puncture and biopsy and immunohistochemical study confirmed pulmonary primitive
      neuroectodermal tumor (PNET). PNET is characterized by small round blue cells and
      positive CD99 expression. After six cycles of chemotherapy with ifosfamide,
      dacarbazine and cisplatin, the lesions diminished substantially. At 2 months
      after the last cycle of chemotherapy, the patient complained of exertional
      dyspnea. PET-CT and echocardiogram suggested a space-occupying lesion in the
      right atrium. Autopsy revealed that this space-occupying lesion had the same
      pathomorphology and immunophenotype with pulmonary PNET, suggesting metastasis of
      pulmonary PNET to the right atrium. Here, we reported this rare case of pulmonary
      PNET metastasizing, instead of direct infiltrating or extending, into the heart.

PMID- 22392201
TI  - Evidence-based medicine: what is taking the jury so long?

PMID- 22392202
TI  - SMJ editor's preface to special issue on evidence-based medicine.

PMID- 22392203
TI  - Evidence-based medicine for clinicians.

PMID- 22392204
TI  - The challenge of evidence-based medicine.

PMID- 22392205
TI  - Evidence-based medicine: specific skills necessary for developing expertise in
      critical appraisal.
AB  - The concept of evidence-based medicine (EBM), defined as the integration of best
      research evidence with clinical expertise and patient values, is essential to the
      review, understanding, and application of clinical principles into the practice
      of medicine. Critical appraisal includes recognizing and evaluating various study
      designs and their ranking in order of priority, judging relevance to the question
      at hand, identifying potential sources of bias, and determining whether the data
      presentation, statistical analysis, and conclusions are appropriate. The focus of
      this article is on the quality of the evidence and how each step in critical
      appraisal is important to the overall concept and application of EBM.

PMID- 22392206
TI  - Statistics for the nonstatistician: A primer for reading clinical studies.

PMID- 22392207
TI  - Statistics for the nonstatistician: Part I.
AB  - Clinical research typically gathers sample data to make an inference about a
      population. Sample data carries the risk of introducing variation into the data,
      which can be estimated by the standard error of the mean. Data are described
      using descriptive statistics such as mean, median, mode, and standard deviation.
      The strength of the relation between two groups of data can be described using
      correlation. Hypothesis testing allows the researcher to accept or reject a null
      hypothesis by calculating the probability that differences between groups are the
      result of chance. By convention, if the probability is less than .05, the
      difference between the groups is said to be statistically significant. This
      probability is determined by statistical tests. Of these groups of tests, the
      Student t test and the analysis of variance are the more common parametric tests,
      and the chi-square test is common for nonparametric tests. This article provides
      a basic overview of biostatistics to assist the nonstatistician with interpreting
      statistical analyses in research articles.

PMID- 22392208
TI  - Statistics for the nonstatistician: Part II.
AB  - Part I of this two-part article provides a foundation of statistical terms and
      analyses for clinicians who are not statisticians. Types of data, how data are
      distributed and described, hypothesis testing, statistical significance, sample
      size determination, and the statistical analysis of interval scale (numeric) data
      were reviewed. Some data are presented not as interval data, but as named
      categories, also called nominal or categorical data. Part II reviews statistical
      tests and terms that are used when analyzing nominal data, data that do not
      resemble a normal, bell-shaped curve when plotted on the x- and y-axes, linear
      and logistic regression analysis, and survival analyses. A comprehensive
      algorithm of appropriate statistical analysis determined by the type, number, and
      distribution of collected variables also is provided.

PMID- 22392209
TI  - Application of the principles of evidence-based medicine to patient care.
AB  - Evidence-based medicine (EBM) is the conscientious and judicious use of the best
      evidence available collected from clinical trials, guidelines, and consensus
      statements. This article provides simple ways to practice EBM using five steps
      (assess the patient, ask a clearly focused clinical question, acquire the best
      evidence available from the medical literature, appraise the evidence, and apply
      the evidence to patient care) and how to execute each step properly, multiple
      examples of how to apply EBM to patient care, and examples of how to apply the
      PICO mnemonic (patient, intervention, comparison, and outcome) to the process of
      EBM.

PMID- 22392210
TI  - Critical appraisal process: step-by-step.
AB  - We present information describing how to search to identify those reports that
      provide insight into the answer to the query. We have presented a reasonable
      approach to searching, with our end-point being the identification of published
      articles which appear to answer our queries. The decision as to whether these
      articles are applicable to the patient under discussion is determined by our
      clinical knowledge and the specifics of the patient's medical concerns. This
      process is recognized as critical analysis. Our structure for optimal searching
      includes use of the PICO model, formulating a focused clinical question, and
      defining key search terms. Using these principles, we have addressed an example
      important controversy in the practice of clinical medicine; in other words, the
      effectiveness of screening for prostate cancer and whether it alters the natural
      history of this illness.

PMID- 22392211
TI  - Impact of patient selection in various study designs:  identifying potential bias
      in clinical results.
AB  - Many different study designs are used to address different types of clinical
      questions. The two broad categories are the experimental study, which is the
      randomized controlled trial, and observational studies, which includes all of the
      other basic study designs (cohort [prospective and retrospective] studies, case
      control [etiologic] studies, cross-sectional [prevalence] studies, case series,
      and case reports). These study designs address basic categories of clinical
      questions: treatment, diagnosis, prognosis, and harm. This article focuses on
      some of these study designs, highlighting the impact of patient selection,
      inclusion, and exclusion criteria on results and outcomes through the use of
      specific examples.

PMID- 22392212
TI  - Challenge of surrogate endpoints.
AB  - Surrogate endpoints are biomarkers that are intended to substitute for clinical
      endpoints. They have been used to find novel therapeutic targets, improve the
      statistical power and shorten the duration of clinical trials, and control the
      cost of conducting research studies. The more generalized use of surrogate
      endpoints in clinical decision making can be hazardous and should be undertaken
      with great caution. This article reviews prior work with surrogate endpoints and
      highlights caveats and lessons learned from studies using surrogate endpoints.

PMID- 22392213
TI  - Arriving at correct conclusions:  the importance of association, causality, and
      clinical significance.
AB  - Declaring that a causal and not solely a correlative relation exists between a
      risk factor and a disease creates significant implications for patients and
      physicians. No matter the forum, when investigators or clinicians make such a
      claim, it is essential to explain how this determination was made so that
      appropriate recommendations are made in all areas of our professional practice.
      When we review the medical literature it is similarly crucial to understand this
      distinction between causality and association. The Bradford Hill criteria of
      strength of association, consistency, temporality, biological gradient,
      biological plausibility, coherence, experimental evidence, and analogy can be
      used to help establish causality. It is also important to understand the
      distinction between clinical and statistical significance to complete our
      appraisal of the implications of a clinical study. Statistically significant
      results, although not the result of chance, may be clinically insignificant.
      Statistically insignificant results, conversely, may not exclude the possibility
      of a clinically important relation. This article reviews the concepts of
      causality and association and clinical versus statistical significance and
      provides examples from the literature.

PMID- 22392214
TI  - Reasoning and evidence-based medicine:  common pitfalls.
AB  - It is impossible to answer every potential clinical question through randomized
      controlled trials. Hence, assumptions, rational thinking, logic, and reasoning
      are used in making recommendations; however, these methods may interfere with the
      judicious application of evidence-based medicine and, as discussed in this
      article, may result in logical fallacies. We also explain how we may incorporate
      recommendations based on assumptions and rational thinking in patient care.
      Extrapolations of study content and confusing association with causation are
      common pitfalls in the application of the evidence-based medicine process.
      Personal bias can be another barrier in the adoption of evidence-based medicine.
      It can be difficult to modify personal bias despite the evidence; keeping up with
      the medical literature in a busy practice can be daunting.

PMID- 22392215
TI  - Final tips in interpreting evidence-based medicine.
AB  - In this issue, the Southern Medical Journal presents a series of articles to help
      students of medicine understand the principles of evidence-based medicine. These
      articles are not meant to be a comprehensive review, but rather an easy-to-read
      primer. In this final article, the authors offer suggestions to aid the reader in
      navigating the ever-expanding amount of information. These tips address a number
      of points that are commonly encountered in the medical literature, but are not
      all-inclusive.

PMID- 22392216
TI  - Development: Many roads lead to commitment.

PMID- 22392218
TI  - Human disease: Germline selection for deleterious mutation in males.

PMID- 22392217
TI  - Regulation of cytoplasmic mRNA decay.
AB  - Discoveries made over the past 20 years highlight the importance of mRNA decay as
      a means of modulating gene expression and thereby protein production. Up until
      recently, studies largely focused on identifying cis-acting sequences that serve
      as mRNA stability or instability elements, the proteins that bind these elements,
      how the process of translation influences mRNA decay and the ribonucleases that
      catalyse decay. Now, current studies have begun to elucidate how the decay
      process is regulated. This Review examines our current understanding of how
      mammalian cell mRNA decay is controlled by different signalling pathways and lays
      out a framework for future research.

PMID- 22392220
TI  - Technology: Cancer-cell-targeting robots.

PMID- 22392221
TI  - Ventricular tachycardia with frequent retrograde P waves.

PMID- 22392222
TI  - Alternating bizarrely-shaped broad QRS complex tachycardia. What is the
      mechanism?

PMID- 22392219
TI  - Metazoan promoters: emerging characteristics and insights into transcriptional
      regulation.
AB  - Promoters are crucial for gene regulation. They vary greatly in terms of
      associated regulatory elements, sequence motifs, the choice of transcription
      start sites and other features. Several technologies that harness next-generation
      sequencing have enabled recent advances in identifying promoters and their
      features, helping researchers who are investigating functional categories of
      promoters and their modes of regulation. Additional features of promoters that
      are being characterized include types of histone modifications, nucleosome
      positioning, RNA polymerase pausing and novel small RNAs. In this Review, we
      discuss recent findings relating to metazoan promoters and how these findings are
      leading to a revised picture of what a gene promoter is and how it works.

PMID- 22392223
TI  - A wider scope on the treatment of atrial fibrillation.

PMID- 22392224
TI  - Improving metallomics information related to transgenic and non-transgenic
      soybean seeds using 2D-HPLC-ICP-MS and ESI-MS/MS.
AB  - This work reports the use of 2D-HPLC-ICP-MS to enlarge metallomics information
      when considering soybean seeds. Separations using size exclusion chromatography
      (SEC) allowed the identification of three metal fractions: the first
      corresponding to molecular weights from 38.1 to 181.1 kDa, the second from 8.2 to
      17.2 kDa and the third from 0.4 to 3.8 kDa. In a second dimension, using anion
      exchange chromatography (AEX), three sub-fractions containing Fe, Mg and Mn, one
      containing Cu, and three containing Co, Cu, Mg, Mn and Zn were obtained. After
      these separations, 33 proteins were identified using the ESI-MS/MS technique, and
      divided into four functional categories: plant growth/cell division, protein
      destination and storage, metabolism and unclassified proteins. Among the
      identified proteins, proteins previously related to metals were found.

PMID- 22392225
TI  - Investigation of encapsulation of insulin biotemplate within C
      methylresorcin[4]arenes.
AB  - Solution structure of insulin templated C-methyl resorcin[4]arene nanocapsules
      has been investigated using neutron scattering. The insulin biotemplate has
      enhanced the limits of encapsulation and enabled formation of a larger spherical
      molecular host.

PMID- 22392226
TI  - Patterns of sheath elongation, cell proliferation, and manganese(II) oxidation in
      Leptothrix cholodnii.
AB  - Leptothrix cholodnii is a Mn(II)-oxidizing and sheath-forming member of the class
      beta-Proteobacteria. Its sheath is a microtube-like filament that contains a
      chain of cells. From a chemical perspective, the sheath can be described as a
      supermolecule composed of a cysteine-rich polymeric glycoconjugate, called
      thiopeptidoglycan. However, the mechanism that controls the increase in sheath
      length is unknown. In this study, we attempted to detect sheath elongation
      through microscopic examination by using conventional reagents. Selective
      fluorescent labeling of preexisting or newly formed regions of the sheath was
      accomplished using combinations of biotin-conjugated maleimide, propionate
      conjugated maleimide, and a fluorescent antibiotin antibody. Epifluorescence
      microscopy indicated that the sheath elongates at the terminal regions. On the
      bases of this observation, we assumed that the newly secreted thiopeptidoglycan
      molecules are integrated into the preexisting sheath at its terminal ends.
      Successive phase-contrast microscopy revealed that all cells proliferate at
      nearly the same rate regardless of their positions within the sheath. Mn(II)
      oxidation in microcultures was also examined with respect to cultivation time.
      Results suggested that the deposition of Mn oxides is notable in the aged
      regions. The combined data reveal the spatiotemporal relationships among sheath
      elongation, cell proliferation, and Mn oxide deposition in L. cholodnii.

PMID- 22392227
TI  - Culture of limbal stem cells on human amniotic membrane.
AB  - Limbal stem cells (LSC) have an important role in the maintenance of the corneal
      surface epithelium, and autologous cultured limbal epithelial cell (HLECs)
      transplantations have contributed substantially to the treatment of the visually
      disabling condition known as LSC deficiency. A major challenge is the ability to
      identify LSC in vitro and in situ, and one of the major controversies in the
      field relates to reliable LSC markers. This study was carried out to evaluate the
      culture of a limbal biopsy on human amniotic membrane (HAM): directly on the
      chorionic side and on intact epithelium, and the expression of the stem cell
      associated markers: ABCG2, p63. HAM has been extensively used for ocular surface
      reconstruction and has properties which facilitate the growth of epithelial cells
      controlling inflammation and scarring.

PMID- 22392228
TI  - Use of irradiated human amnion as a matrix for limbal stem cell culture.
AB  - Several ocular diseases affect the corneal surface; the development of effective
      technologies for the treatment of corneal lesions has brought about an
      improvement in the quality of life of affected patients. The aim of this study is
      to culture and characterize limbal stem cells cultured on gamma ((60)Co)
      radiosterilized human amnion (RHA). Limbal stem cells were isolated from ten
      preserved samples of corneal transplant. The cells were cultured since primary
      culture until expanded cells on RHA and stained with monoclonal antibodies to
      establish their immunophenotype, after which cytokeratin 12 and Vimentin were
      positive by immunohistochemistry. The immunophenotype remained constant since
      primary culture until expanded cells in RHA. The RHA and cells construct were
      structurally integrated. Immunohistochemistry was cytokeratin 12, Vimentin
      positive, and cytokeratin 19 negative. In vitro limbal cells maintain a constant
      epithelial transition immunophenotype in culture up to primary culture until
      expanded cells on RHA.

PMID- 22392229
TI  - Mineralization of pentachlorophenol with enhanced degradation and power
      generation from air cathode microbial fuel cells.
AB  - The combined anaerobic-aerobic conditions in air-cathode single-chamber MFCs were
      used to completely mineralize pentachlorophenol (PCP; 5 mg/L), in the presence of
      acetate or glucose. Degradation rates of 0.140 +/- 0.011 mg/L-h (acetate) and
      0.117 +/- 0.009 mg/L-h (glucose) were obtained with maximum power densities of
      7.7 +/- 1.1 W/m(3) (264 +/- 39 W/m(2), acetate) and 5.1 +/- 0.1 W/m(3) (175 +/- 5
      W/m(2), glucose). At a higher PCP concentration of 15 mg/L, PCP degradation rates
      increased to 0.171 +/- 0.01 mg/L-h (acetate) and 0.159 +/- 0.011 mg/L-h
      (glucose). However, power was inversely proportional to initial PCP
      concentration, with decreases of 0.255 W/mg PCP (acetate) and 0.184 W/mg PCP
      (glucose). High pH (9.0, acetate; 8.0, glucose) was beneficial to exoelectrogenic
      activities and power generation, whereas an acidic pH = 5.0 decreased power but
      increased PCP degradation rates (0.195 +/- 0.002 mg/L-h, acetate; 0.173 +/- 0.005
      mg/L-h, glucose). Increasing temperature from 22 to 35 degrees C enhanced power
      production by 37% (glucose) to 70% (acetate), and PCP degradation rates (0.188 +/
      0.01 mg/L-h, acetate; 0.172 +/- 0.009 mg/L-h, glucose). Dominant exoelectrogens
      of Pseudomonas (acetate) and Klebsiella (glucose) were identified in the
      biofilms. These results demonstrate that PCP degradation using air-cathode single
      chamber MFCs may be a promising process for remediation of water contaminated
      with PCP as well as for power generation.

PMID- 22392230
TI  - A comparison between time to clinical stability in community-acquired aspiration
      pneumonia and community-acquired pneumonia.
AB  - Antimicrobial therapy has been the main stay of therapy of community-acquired
      aspiration pneumonia (CAAP), but the duration of treatment has not been
      established. The objective of this study was to describe the time to reach
      clinical stability in patients with aspiration pneumonia compared to community
      acquired pneumonia (CAP). A retrospective case control study at two university
      affiliated centers encompassing 329 consecutive patients admitted with CAAP and
      329 consecutive patients with CAP was conducted between 2007 and 2011. While the
      median time to stability for patients with CAP was distributed around a median of
      4 days, there was a bimodal distribution for time to clinical stability in
      patients with CAAP with dual peaks at days 2 and 5, respectively. CAAP patients
      who required more than 2 days to achieve clinical stability had a higher
      mortality rate compared to those with 2 days or less [odds ratio (OR) 5.95, 95%
      CI 2.85-12.4], and a longer hospital stay (6.6 +/- 5.8 vs. 3.9 +/- 1.2 days; p <
      0.001). None of the CAAP patients who achieved clinical stability in 2 days or
      less was transferred to a higher level of care. In a multivariate analysis, time
      to clinical stability was found to be an independent predictor of outcome in
      patients with CAAP (OR 2.59, 95% CI 2.02-3.32). Normalization of vital signs in
      aspiration pneumonia follows a distinct pattern from that of patients with CAP.
      Time to achieve clinical stability may assist in identifying CAAP patients who
      are likely to require a shorter hospital stay and a shorter course of
      antimicrobial therapy.

PMID- 22392231
TI  - Directions of the bilateral cochlear implant in Brazil.

PMID- 22392232
TI  - The influence of the type of breastfeeding on middle ear conditions in infants.
AB  - Infants should be submitted to hearing screening upon birth, and for the results
      to be complete, it is necessary to assess middle ear conditions. OBJECTIVE: To
      check whether the type of breastfeeding in infants between zero and four months
      can impact middle ear conditions my means an ENT assessment and acoustic
      immittance comparing neonates who were submitted to hearing screening with those
      who failed it. MATERIALS AND METHODS: Otoacoustic emissions (OAE) was carried out
      in 60 infants between zero and four months. They were distributed in two groups;
      group I had the infants with OAE and those infants in group II did not have OAE.
      They were submitted to tympanometry with a 1000 Hz test tone and ENT assessment.
      RESULTS: Bottle fed infants or those who were fed in a mixed way had more changes
      to their audiometry and ENT assessment, with a statistically significant
      difference. The breastfed infants had a higher occasion of normal tympanometries
      and normal otorhinolaryngological assessment, with statistically significant
      difference. CONCLUSION: We then concluded that those breastfed implants had less
      ENT changes and as well as less acoustic immittance change, thus enabling OAEs.
      Breastfeeding alone can be considered a protection factor against middle ear
      changes.

PMID- 22392233
TI  - Children with cochlear implants: communication skills and quality of life.
AB  - Given the multidimensional scope of cochlear implants, there is a growing need to
      assess clinical measures related communicative abilities and more general aspects
      involved in the effectiveness of treatment, such as quality of life. AIM: To
      translate and adapt an international questionnaire of quality of life to
      Brazilian Portuguese; to apply the questionnaire in parents of children with
      cochlear implant to assess quality of life of children after cochlear
      implantation; to analyze correlations among factors related to quality of life;
      to analyze correlations between quality of life and clinical measures of outcome.
      METHOD: Prospective study in which parents of children with cochlear implants
      responded to validated instruments on quality of life and communication
      abilities. RESULTS: The translation and adaptation of the questionnaire was
      satisfactorily completed. According to the data, cochlear implants had a positive
      effect on quality of life of the implanted children and their families. Observed
      correlations for the variable communication demonstrate a direct relationship
      between oral communication and other variables of quality of life. CONCLUSIONS:
      This study makes this questionnaire available in Brazilian Portuguese. For
      parents of Brazilian children with cochlear implants, lexical
      development(acquisition and use of words) is the variable that relates most to
      the quality of life of their children.

PMID- 22392234
TI  - Retrospective analysis of 26 cases of inverted nasal papillomas.
AB  - Inverted papilloma (IP) comprises 0.5-4% of benign nasal tumors. The importance
      is shown by local aggressiveness, a high recurrence rate and the possibility of
      malignant transformation. The treatment is controversial, but endoscopic
      approaches tends to be the choice today. AIM: To describe clinical,
      epidemiological and treatment of IP cases in a tertiary hospital. METHODS:
      Retrospective study consisting of chart reviews of 26 patients diagnosed with IP;
      evaluation of tumor location, clinical staging, follow up, tumor recurrence,
      malignancy, type of surgery and postoperative complications. RESULTS: There were
      13 men and 13 women, the mean age was 57.8 years. The mean follow up time was
      29.4 months; the recurrence rate was 7.6%. There was a preponderance of T3 and T4
      tumors and a 3.8% malignancy rate. All patients underwent surgical treatment,
      mostly endonasal endoscopic surgery. CONCLUSION: IP is an uncommon nasal tumor
      that originates mainly in the lateral nasal wall, but it also affects the
      paranasal sinuses. Advances in endoscopic surgery are gaining room due to lower
      invasiveness and success rates similar to traditional external techniques for
      completely resecting the tumor. There is a lower recurrence rate, and endoscopy a
      definitive treatment for malignancy cases in this study.

PMID- 22392235
TI  - Cochlear implant radiography: technique adapted into a portable apparatus.
AB  - The unavailability of advanced imaging equipment in the operating rooms of most
      hospitals - as well as the fundamental importance for surgeons of immediate
      observation of the cochlear implants soon after their insertion - makes
      conventional radiography a good option. OBJECTIVE: To describe a practical, fast
      and low-cost radiographic method, allowing for evaluation of the electrodes
      regarding their position and integrity, during the insertion of cochlear
      implants. MATERIALS AND METHODS: Radiographies from 262 cochlear implant patients
      were analyzed, from March 2005 to October 2008, by means of intraoperative
      radiography, soon after electrode insertion. All radiographies were analyzed by
      the surgeon in the intraoperative period and, afterwards, by the radiologist.
      RESULTS: A total of 524 radiographies were analyzed, and 95.61% presented
      adequate technique--with the patient being positioned into the technique proposed
      in this study--as well as a clear visualization of the electrodes, regarded as
      satisfactory. On the other hand, 4.39% presented inadequate technique and/or
      unsatisfactory visualization of the electrodes, regarded as unsatisfactory.
      CONCLUSION: Although the portable X-ray apparatus presents limitations, the
      employment of proper techniques and accessories makes possible the obtainment of
      satisfactory radiographies to observe cochlear implants.

PMID- 22392236
TI  - Method for removal of samples of ear canal and tympanic membrane for histologic
      and immunhistochemical study.
AB  - Temporal bones are valuable resources to study ear diseases. Although there are
      several methods for removing temporal bones from cadavers, such methods are not
      usually described in enough details in experimental research papers. OBJECTIVES:
      To describe a simple and rapid method for ear canal and tympanic membrane
      removal, and to evaluate its viability for histologic and immunohistochemical
      studies. MATERIALS AND METHODS: In this experimental study, we obtained 31 ear
      canal and tympanic membrane samples from cadavers, with a conventional power
      drill and plug cutter. The material was dissected and samples containing ear
      canals and tympanic membranes were obtained in blocks. The samples were analyzed
      by histology and immunohistochemistry. RESULTS: Removal of small and good quality
      samples containing entire ear canals and tympanic membranes. In all the samples,
      it was possible to perform both histological and immunohistochemical analyses.
      CONCLUSION: This method was easily achievable, reproducible and yielded good
      quality samples, both for training purposes and for experimental research. All
      the samples were viable for histological and immunohistochemical analyses.

PMID- 22392237
TI  - Electro acoustic stimulation of the auditory system: UNICAMP's surgical approach.
AB  - A new era has arrived in auditory rehabilitation with the introduction of new
      technologies such as electroacoustic stimulation (EAS). EAS is indicated for
      patients with residual hearing at low frequencies and severe or profound hearing
      loss at high frequencies. These patients have no indication for conventional
      cochlear implant and have difficulties in adapting to individual sound
      amplification devices. Preservation of hearing is vital in this process; the
      surgical technique must be based on this concept. OBJECTIVES: To present the
      cochlear implant surgical technique with MED-EL Mand FlexEAS to preserve hearing
      in patients with hearing loss at high frequencies and to maintain low frequency
      hearing. We are the first institution to carry out this treatment in Brazil.
      METHODS: A case report of the surgical technique carried out in four patients;
      the procedure was carried out by the cochlear implant group of a specialized
      clinical hospital. RESULTS: The procedures were successful and uneventful.
      CONCLUSION: We described the technique used at our institution for implants using
      EAS; the surgical technique is complex and includes steps for preservation of
      hearing.

PMID- 22392238
TI  - Influence of sealant fibrin on the wound healing of the pigs vocal folds.
AB  - Fibrin sealants or fibrin glue are products made from human plasma proteins,
      which mimic the final pathway of the coagulation cascade. Its application to
      stimulate the healing process has been a topic of debate in the literature. The
      use of fibrin sealants in phonosurgery has been empirical; there have been no
      studies that investigate the action of fibrin sealant in Reinke's space. AIM: To
      evaluate the effect of fibrin glue in healing of the vocal folds of pigs after
      surgical manipulation. MATERIALS AND METHODS: This was a prospective and
      experimental study. Six animals had both vocal folds incised. Sealant was applied
      in one of them; the other served as a control. After three months, the animals
      were sacrificed and a collagen count was carried out. RESULTS: The side on which
      glue was applied had an average of 27.8% against 20.4% of the side without glue.
      CONCLUSION: The collagen concentration in the samples where the fibrin sealant
      was applied was significantly higher compared to samples without glue. Thus, the
      presence of a fibrin sealant stimulates fibrogenesis in this tissue.

PMID- 22392239
TI  - Risk factors for incidental parathyroidectomy during thyroidectomy.
AB  - Incidental parathyroidectomy is a common event in thyroid surgery. The literature
      shows a finding of parathyroid glands ranging from 6.4% to 31% in pathological
      specimens of the thyroid gland. OBJECTIVE: To collect the amount of parathyroid
      glands found in surgical specimens of thyroidectomy and correlate with the
      histopathological and demographic variables. METHODS: Retrospective study based
      on pathological reports of thyroidectomy from January 2007 to December 2008.
      RESULTS: 442 patients were submitted to total thyroidectomy, and 2.93% had
      parathyroid glands, which corresponded to 13 of this total. The presence of
      papillary thyroid carcinoma associated with incidental parathyroidectomy was
      10.11%, compared to the benign lesion: 1.4%. CONCLUSION: Papillary thyroid
      carcinoma was the variable associated with increased number of incidental
      parathyroidectomy.

PMID- 22392240
TI  - Correlation between vestibular test results and self-reported psychological
      complaints of patients with vestibular symptoms.
AB  - Cognitive and emotional factors may affect balance; psychiatric conditions are a
      common component in patient dizziness. The treatment of patients with vertigo may
      be affected to a greater degree by the suffering due to this disease than by the
      severity of organic changes. OBJECTIVE: This study aimed to investigate
      associations between vestibular test results and self-reported psychological
      complaints in patients evaluated during 2009 in an audiology unit at a hospital
      in Porto Alegre. METHODS: We conducted a retrospective, descriptive-exploratory
      study of data taken from a database of the software VecWin(r) and VecWin(r) 2,
      developed by Neurograff(r). We investigated vestibular test results, reports of
      psychological symptoms reported spontaneously, and information such as age, sex
      and the presence of vertigo and/or dizziness. This study consisted of three
      steps: clustering, exclusion/inclusion and quantification. CONCLUSION: Age and
      gender and the presence or absence of vertigo and/or dizziness were not variables
      that influenced the outcomes of vestibular testing. There was a significant
      association between the presence of self-reported psychological complaints and
      normal vestibular test results. Thus, it is crucial that professionals pay
      attention to psychological issues reported by patients when the vestibular
      history is taken.

PMID- 22392241
TI  - Antimicrobial activity of Terminalia arjuna Wight & Arn.: an ethnomedicinal plant
      against pathogens causing ear infection.
AB  - Ear infection is one of the common diseases occurring throughout the world.
      Different etiological agents are responsible for ear infections. AIM: To assess
      the antimicrobial potential of Terminalia arjuna leaves and bark extracts against
      Staphylococcus aureus, Acinetobacter sp., Proteus mirabilis, Escherchia coli,
      Pseudomonas aeruginosa and Candida albicans, pathogens causing ear infections and
      their comparison with locally available ear drops. MATERIALS AND METHODS:
      Methanol, ethanol, acetone, aqueous (hot and cold) extracts from the leaves and
      bark of T. arjuna were tested for their antimicrobial activity. RESULTS: Of the
      three organic solvents evaluated, acetonic leaf extract was found to be best
      against S. aureus. Organic bark extract showed almost equal inhibition of all
      tested Gram negative bacteria except P. aeruginosa. However, aqueous extract of
      T. arjuna bark exhibited good activity against S. aureus. All the extracts were
      unable to exhibit any antifungal activity. CONCLUSION: Organic extract obtained
      from the T. arjuna bark and leaves may be used to treat the bacterial ear
      pathogens especially S. aureus, which has shown greater inhibition zones than the
      herbal drops, however, we still need more detailed studies as in vivo testing and
      pharmacokinetics properties for their therapeutic utility in treating ear
      infections.

PMID- 22392242
TI  - Comparison between endoscopic and open surgery in 37 patients with nasopharyngeal
      angiofibroma.
AB  - Juvenile nasopharyngeal angiofibroma is a rare benign vascular tumor of the
      nasopharynx. Although the treatment of choice is surgery, there is no consensus
      on what is the best approach. AIM: To compare surgical time and intraoperative
      transfusion requirements in patients undergoing endoscopic surgery versus open /
      combined and relate the need for transfusion during surgery with the time between
      embolization and surgery. MATERIAL AND METHODS: Study descriptive, analytical,
      retrospective study with a quantitative approach developed in the
      Otorhinolaryngology department of a teaching hospital. Analyzed 37 patients with
      angiofibroma undergoing surgical treatment. Data obtained from medical records.
      Analyzed with tests of the Fisher-Freeman-Halton and Games-Howell. Was considered
      significant if p <0.05. STUDY DESIGN: Historical cohort study with cross
      sectional. RESULTS: The endoscopic approach had a shorter operative time (p
      <0.0001). There is less need for transfusion during surgery when the embolization
      was performed on the fourth day. CONCLUSION: This suggests that the period ahead
      would be ideal to perform the process of embolization and endoscopic surgery by
      demanding less time would be associated with a lower morbidity. This study,
      however, failed to show which group of patients according to tumor stage would
      benefit from specific technical.

PMID- 22392243
TI  - pH salivary analysis of subjects suffering from Sjogren's syndrome and
      laryngopharyngeal reflux.
AB  - Saliva is one of the components for the digestive homeostasis. Recent studies
      have shown that patients with laryngopharyngeal reflux (LPR) present a drop in
      salivary pH. Patients with Sjogren's syndrome (SS) are a potential clinical
      research model for xerostomia and its laryngeal and pharyngeal consequences. The
      aim was to evaluate the characteristics of saliva of patients with SS and LPR.
      METHODS: 19 patients with SS plus LPR, and 12 healthy controls had their saliva
      studied prospectively for volume and pH. Two salivary samples were obtained from
      each participant: whole unstimulated saliva(WUS) and whole stimulated saliva(WSS)
      while chewing parafilm M(r). All the participants were females. RESULTS: Mean age
      was 60 years (study group) and 44 years (control). LPR was diagnosed on all 19
      subjects. The mean pH of WUS was 7.53 (SS) and 7.57 (controls), raising to 7.87
      and 7.83 respectively after stimulation. The mean salivary volume of patients
      with SS was 1.27 mL (WUS) and 3.78 mL (WSS), whereas controls had a significantly
      higher salivary volume both before and after stimuli. CONCLUSION: A very high
      prevalence of LPR was found in patients with SS, which is probably caused by a
      uniform drop in salivary volume and all its contents, rather than a specific
      deficiency in its components, as shown previously in patients without SS.

PMID- 22392244
TI  - Occurrence and suppression effect of otoacoustic emissions in normal hearing
      adults with tinnitus and hyperacusis.
AB  - The association between tinnitus and hyperacusis is common according to the
      literature. AIM: To verify the occurrence and the suppression effect of transient
      otoacoustic emissions (TEOAE), the existence of association between tinnitus
      degrees and hyperacusis degrees, and between the suppressive effect of TEOAE and
      laterality, tinnitus and hyperacusis degrees in normal hearing adults with
      complaints of tinnitus and hyperacusis. MATERIALS AND METHODS: 25 normal hearing
      subjects with complaints of hyperacusis and tinnitus were studied in this cross
      sectional study. The Tinnitus Handicap Inventory (THI) was used for the
      classification of tinnitus degrees, and the Loudness Discomfort Level (LDL) for
      the hyperacusis classification. RESULTS: The occurrence of TEOAE ranged from 33
      to 88%. We observed the presence of TEOAE suppression effect on 63.7% in the
      right ear and 81.7% in the left ear. There was no significant correlation between
      the degrees of tinnitus and hyperacusis in both ears. No statistically
      significant associations between the TEOAE suppression effect and laterality,
      tinnitus degrees and hyperacusis degrees were found. CONCLUSION: The occurrence
      of TEOAE was lower than that found in normal hearing adults. A higher percentage
      of the presence of TEOAE suppression effect has been found in both ears. No
      association between the variables was observed.

PMID- 22392245
TI  - Tympanometry with 226 and 1000 Hertz tone probes in infants.
AB  - This study aimed at describing and analyzing tympanometric results obtained with
      226 Hz and 1000 Hz probe tones; checking for correlations between tympanometry,
      otoacoustic emissions and otoscopic examination; describing abnormal results
      found in the evaluation procedures. METHODS: Double-blind and prospective study.
      Our sample included 70 babies, between 7 days and one month and 13 days of age,
      without risk indicators for hearing loss, evaluated in the State Neonatal Hearing
      Screening Program. Transient evoked otoacoustic emissions, otoscopic examination
      and tympanometry with 226 Hz and 1000 Hz probe tones were used as assessment
      tools. The study was approved by the Ethics Committee from the institution.
      RESULTS: Statistically significant differences were observed (p<0.05) in the
      tympanometric measures correlation and also between transient evoked otoacoustic
      emissions and compliance obtained with both probe tones. Most test results were
      within the normal range (94.28%). Three children (4.28%) were referred to
      diagnostic follow-up and one (1.42%) had middle ear dysfunction confirmed by
      otoscopy and 1000 Hz tympanometry. CONCLUSIONS: 1000 Hz tympanometry is the most
      reliable probe tone used to evaluate children under three months of age. More
      studies focusing on middle ear acoustics and mechanics are necessary to provide
      reliable and precise interpretation in the evaluation of middle ear functions in
      babies.

PMID- 22392246
TI  - Comparison of the area of the pharynx during wakefulness and induced sleep in
      patients with obstructive sleep apnea (OSA).
AB  - The study of obstructive sleep apnea (OSA) has received growing attention over
      the past years since various aspects have not been sufficiently established. AIM:
      To evaluate, with the use of magnetic resonance imaging (MRI), changes in the
      area of the pharynx during wakefulness and induced sleep in patients with OSA.
      MATERIALS AND METHODS: A prospective study of thirty-two patients with a
      polysomnographic diagnosis of OSA. All patients were submitted to MR imaging in
      order to obtain high-definition anatomical sagittal sequences during wakefulness
      and during sleep induced with Propofol. An area was defined on the sagittal plane
      in the midline of the pharynx. This region was called pharyngeal midplane (PMP)
      area. RESULTS: A significant difference in PMP area (mm2) was observed between
      wakefulness and induced sleep in each patient (p < 0.000001). CONCLUSION: The
      patients with OSA suffer a significant reduction of 75.5 % in the area of the
      pharynx during induced sleep compared to wakefulness.

PMID- 22392247
TI  - Middle ear implants: functional gain in mixed hearing loss.
AB  - Osseous atresia and chronic otitis media are diseases benefit with middle ear
      implants. Surgery for atresia is technically complicated, has significant number
      of complications and functional results are often poor. The osseointegrated
      hearing aids are an alternative. They provide a very good functional gain, but
      have many problems with the skin and osseointegration. In chronic otitis media,
      the ossiculoplasty solved partially the hearing problem. Unfortunately in some
      cases of otitis media and in open cavities fitted with conventional hearing aids
      the gain is unsatisfactory. AIM: To determine the usefulness of an active middle
      ear implant. MATERIAL AND METHOD: Longitudinal Study. Vibrant-Soundbrigde was
      implanted in eight patients with severe mixed hearing loss. Four patients had
      chronic otitis media and four had unilateral atresia. The placement of the
      stimulator (FMT or Floating Mass Transducer) was in five patients on round
      window, two in stapes and one in the oval window. RESULTS: Functional gain was 35
      dB, 40 dB, 48.7 dB and 50 dB for the frequencies 500, 1000, 2000 and 4000 Hz,
      respectively. CONCLUSION: Vibrant-Soundbrigde is an excellent option in hearing
      recovery in severe and profound mixed hearing loss. It also provides an excellent
      functional gain in diseases difficult to treat with conventional hearing aids.

PMID- 22392248
TI  - Using ERG inquiry to evaluate otoplasty satisfaction in an otorhinolaryngology
      medical residency training hospital.
AB  - The ear deformity surgery intervention impact on psychological and self-esteem
      aspects, in adults and children, is well documented. Recently, the studys are
      focused on patient satisfaction, funcional result and impact on quality of life.
      Any modification on patient's quality of life has been a challenge. The use of
      valid and established questionnairies, like Glasgow Benefit Inventory (GBI),
      assists on data analyse, turning it consistent. AIM: The aim of this study is to
      evaluate the impact on patients quality of life after otoplasty, through the GBI
      questionnaire. METHODS: Retrospective study including patients underwent
      otoplasty, within july of 2009 to july of 2010. The data were collected through
      questionnaire applied by medical resident on 90 post-surgical return. RESULTS: 36
      patients answered the questionnaire. There was increase on patients quality of
      life demonstrated by positive mediana obtained through out questinnaire. There
      were no significantly differences between age and sex. CONCLUSION: The patients
      are satisfied with post-surgical results. There was increase on patients quality
      of life conform positive results obtained. The use of GBI showed easy and
      elucidative.

PMID- 22392249
TI  - Cephalometric evaluation of the oropharyngeal space in children with atypical
      deglutition.
AB  - For several factors, not yet fully explained until now, infant deglutition may
      persist after changing the primary teeth and such swallowing is classified as
      atypical swallowing. Possible causes: finger sucking, bottle feeding, sucking the
      tongue and mouth breathing. There is no consensus about the etiology of atypical
      deglutition. OBJECTIVE: The aim of this study was to compare the oropharyngeal
      space in side-view radiographs of children with atypical deglutition and normal
      deglutition. METHODS: Retrospective study, by means of cephalometric analysis of
      side-view radiographs, measuring the anteroposterior distance of the lumen of the
      airway in two groups: 55 cephalograms from the experimental group (with atypical
      deglutition) and 55 side-view radiographs from the control group (normal
      deglutition). Measurements from the groups were compared using Mann-Whitney U
      test and a p value <0.05 was considered as an indication of statistical
      significance. RESULTS: The median in the control group was 10 mm and in the
      experimental group it was 7 mm, with a statistically significant difference (p
      <0.001). CONCLUSION: The oropharyngeal space is reduced in the group with
      atypical deglutition.

PMID- 22392250
TI  - Sickle cell anemia and hearing loss among children and youngsters: literature
      review.
AB  - Sickle cell anemia is still a significant public health issue in underdeveloped
      and developing countries. Sickle cell disease is one of the most common inherited
      diseases in Brazil. It affects mainly the mixed race population. Approximately 1
      African-Brazilian child is affected with sickle cell disease for every 37,400
      children born alive. Hearing loss has been considered one of the main clinical
      manifestations, especially in children. However, to date, there are just a hand
      full of studies in Brazil and the Brazilian state of Bahia has the largest
      African-descended population, attempting to establish the frequency of this
      event. OBJECTIVES: To analyze the major studies associated with the subject,
      published in the last twenty years in the main indexed databases. METHODS: To use
      MEDLINE to identify the main papers published in English in medical literature,
      between January of 1989 and January of 2009; associating sickle cell anemia and
      hearing loss, with its clinical outcomes. CONCLUSION: Given that it is always
      possible to attempt to prevent disabilities, understanding hearing loss in
      children with sickle cell anemia enables to maximize quality of life and provides
      for a broader school attendance.

PMID- 22392251
TI  - Head and neck cancer: genetic polymorphisms and folate metabolism.
AB  - Epidemiological evidence suggests that genetic variants encoding enzymes involved
      in folate metabolism may modulate HNSCC risk by altering DNA methylation
      synthesis and genomic estability. AIM: A review of the literature on genetic
      polymorphisms involved in folate metabolism and risk of head and neck cancer was
      carried out. METHODOLOGY: An electronic search was made on the Medline database
      to select papers on head and neck cancer and polymorphisms involved in folate
      metabolism. RESULTS: The association between MTHFR C677T polymorphism and the
      risk of this tumor type was evaluated in nine studies; there was an association
      with this disease in three papers. The MTR A2756G and MTRR A66G and RFC1 A80G
      polymorphisms were also associated with increased risk for HNSCC. MTHFD1 G1958A
      polymorphism was not associated with increased risk of this disease; the
      evaluation results of the MTHFR A1298C polymorphism in this neoplasm were
      contradictory. Other polymorphisms involved in folate metabolism were not studied
      for this neoplasm. CONCLUSION: We conclude that polymorphisms involved in folate
      metabolism may modulate the risk of head and neck cancer, however, these results
      need to be demonstrated in different populations.

PMID- 22392252
TI  - Laryngotracheoplasty in a low birth weight preterm newborn.

PMID- 22392253
TI  - Catheterization of Stenon's duct for surgical excision of oral fibroepithelial
      hyperplasia.

PMID- 22392254
TI  - Surgical approach in a patient with multiple symmetrical lipomatosis: case
      report.

PMID- 22392255
TI  - Subglottic hemangiome in childhood.

PMID- 22392256
TI  - Changes in ribosomal protein S3 immunoreactivity and its protein levels in the
      gerbil hippocampus following subacute and chronic restraint stress.
AB  - Ribosomal protein S3 (rpS3), a multi-functional protein, has been known to
      participate in DNA repair mechanism. In this study, we investigated changes in
      rpS3 immunoreactivity and its protein levels in the sub-regions of the gerbil
      hippocampus following subacute and chronic restraint stress. Serum corticosterone
      levels were increased in both the subacute and chronic-stress-groups compared to
      the control-group: the level in the subacute-stress-group was much higher than
      that in the chronic-stress-group. We could not find any neuronal damage in all
      the sub-regions of the hippocampus after both the subacute and chronic restraint
      stress. In the subacute-stress-group, rps3 immunoreactivity was not different
      compared to the control-group. However, rps3 immunoreactivity in the chronic
      stress-group was decreased compared to the subacute-stress-group: especially, the
      immunoreactivity was markedly decreased in the pyramidal cells of the hippocampus
      proper (CA1-CA3 region) and granule cells of the dentate gyrus. In addition,
      western blot analysis also showed that rpS3 protein levels in the chronic-stress
      group were significantly decreased compared to those in the subacute-stress
      group. These findings indicate that chronic stress, not subacute stress, can
      decrease rpS3 immunoreactivity.

PMID- 22392257
TI  - Structural characterization of monosialo-, disialo- and trisialo-gangliosides by
      negative ion AP-MALDI-QIT-TOF mass spectrometry with MS(n) switching.
AB  - The atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI)
      is a quite convenient soft ionization for biomolecules, keeping analytes
      atmospheric conditions instead of high vacuum conditions. In this study, an AP
      MALDI ion source has been coupled to a quadrupole ion trap time-of-flight (QIT
      TOF) mass spectrometer, which is able to perform MS(n) analysis. We applied this
      system to the structural characterization of monosialogangliosides, GM1 (NeuAc)
      and GM2 (NeuAc), disialogangliosides, GD2 (NeuAc, NeuAc), GD1a (NeuAc, NeuAc) and
      GD1b (NeuAc, NeuAc) and trisialoganglioside GT1a (NeuAc, NeuAc, NeuAc). In this
      system, the negative ion mass spectra of MS, MS(2) and MS(3), a set of three mass
      spectra, were able to measure within 2 s per cycle. Thus, obtained results
      demonstrate that the negative ion mode MS, MS(2) and MS(3) spectra provided
      sufficient information for the determination of molecular weights,
      oligosaccharide sequences and ceramide structures, and indicate that the AP-MALDI
      QIT-TOF mass spectrometry keeping analytes atmospheric conditions with MS(n)
      switching is quite useful and convenient for structural analyses of various types
      of sialic acid-containing GSLs, gangliosides.

PMID- 22392258
TI  - Social use of language in children with reactive attachment disorder and autism
      spectrum disorders.
AB  - Children with a diagnosis of reactive attachment disorder (RAD) appear to show
      difficulties in social understanding. We aimed to compare the pragmatic language
      functioning of children with (RAD) and autism spectrum disorder (ASD).
      Assessments were made in three groups of children aged 5-8 years, with verbal IQ
      estimates in the normal range: 35 with a RAD diagnosis, 52 with an ASD diagnosis
      and 39 with typical development. The Children's Communication Checklist (CCC) was
      used to compare their pragmatic language skills, and ADI-R algorithms were used
      to compare autistic symptomatology, according to parent report. According to the
      CCC, the RAD group demonstrated significant problems in their use of context,
      rapport and social relationships with a degree of severity equivalent to children
      in the ASD comparison group. More than 60% of the group with RAD met ADI-R
      clinical criteria on the Use of Language and Other Social Communication Skills
      subscale, 46% on the Reciprocal Social Interaction subscale, and 20% had
      significant repetitive and stereotyped behaviours. Children with RAD appear to be
      at least as impaired as children with ASD in certain domains of social
      relatedness, particularly in their pragmatic language skills.

PMID- 22392260
TI  - PCP-bridged chalcogen-centred anions: coordination chemistry and carbon-based
      reactivity.
AB  - Since the discovery of the stabilising influence of thiophosphinoyl groups in
      methanediides by Le Floch et al. (Angew. Chem. Int. Ed., 2004, 43, 6382),
      numerous transition metal, lanthanide and actinide complexes of
      bis(thiophosphinoyl) carbene ligands have been investigated with an emphasis on
      the electronic structure and reactivity of the metal-carbon bonds. This
      Perspective begins by discussing main group (s- and p-block) complexes of this
      ligand and draws attention to differences compared to their d and f-block
      analogues. Investigations targeting the heavy chalcogen analogues of the Le Floch
      ligand have revealed an unusual carbon-based reactivity that led to the discovery
      of novel multidentate chalcogen-centred ligands as both monomers and, upon
      oxidation, dimers linked by dichalcogenido functionalities. Studies of main group
      and coinage metal complexes have established the flexibility and redox-activity
      of these novel anionic ligands.

PMID- 22392259
TI  - Modified tension band for displaced type 2 lateral end clavicle fractures.
AB  - PURPOSE: Displaced type 2 lateral end clavicle fractures have a tendency to
      delayed union or non-union. Various methods of stabilisation of the displaced
      lateral end fractures are described. The increasing use of implants to fix such
      fractures also necessitates extensive dissection for implant retrieval. Adequate
      reduction and minimal tissue trauma during implant placement and removal would be
      ideal modalities for fixation of such fractures. METHODS: All displaced type 2
      lateral end clavicle fractures fulfilling our inclusion criteria were reduced
      with a small anterosuperior incision. Anteroposterior drill holes were made in
      both the fragments and a nonabsorabable polyester suture was passed through. The
      fracture was reduced and fixed with transacromial smooth Kirshner wires. The
      suture was tied with the knot superiorly in a figure-eight manner. The arm was
      supported in an arm pouch for six weeks. The Kirshner wire was routinely removed
      after six weeks in an out-patient department. Clinico-radiological outcome was
      studied at six weeks, and monthly intervals thereafter until union. RESULTS: All
      16 fractures united. The mean average age of patients was 36.25 years with a SD
      of 11.35. There was no loss of reduction even after removal of Kirshner wires at
      six weeks. The mean average time of union was 10.75 weeks with a SD of 3.92. All
      patients regained near normal range of motion, and the mean average constant
      score at the end of one year was 98.37 with a SD of 2.87. All patients returned
      to preinjury level by the one-year follow-up. The range of motion remained the
      same in those who were followed up in successive years. Skin impingement with
      bent Kirshner wires were noted in four cases. Kirshner wires backed out in one
      case before six weeks but there was no loss of reduction. Infection and Kirshner
      wire breakage were not noted in our series. CONCLUSION: The clinico-radiological
      outcomes with our modified tension band fixation for displaced type 2 lateral end
      clavicle fractures were encouraging and comparable with earlier studies.

PMID- 22392261
TI  - Getting used to academic public speaking: global self-esteem predicts habituation
      in blood pressure response to repeated thesis presentations.
AB  - Global self-esteem was tested to predict quicker cardiovascular adaptation during
      stressful oral thesis presentation and faster habituation from the first to the
      second and third thesis presentations. Nineteen graduate students initially rated
      their global self-esteem and afterwards orally presented their theses proposals
      in 20-min presentations to their thesis supervisor and peers. A second and third
      presentation of the revised thesis concepts took place at 4-weeks intervals.
      Ambulatory blood pressure and heart rate were assessed repeatedly during the
      presentations. Post-talk self ratings of stressfulness indicated presentations to
      be a strong public speaking stressor. One hundred and thirty-eight measurements
      of systolic (SBP), diastolic blood pressure (DBP), and heart rate (HR) showed a
      significant adaptation (decrease) during presentations. There was an overall mean
      level decrease from the first to the second, and the second to the third
      presentations in HR, but not in SBP and DBP. However, habituation in SBP and DBP
      across three presentations was significantly faster (p < .05) in those
      participants who initially reported higher levels of global self-esteem. Higher
      global self-esteem did not foster adaptation within the presentations. Self
      esteem is discussed as an important individual resource that allows successful
      coping with recurring evaluative threats.

PMID- 22392262
TI  - [Objective structured clinical examination (OSCE) on completion of surgical block
      practical training--twelve months experience with a hands-on examination].
AB  - BACKGROUND: According to the approval system for medical doctors, practical
      courses such as block practical training must be graded. The grading of the
      surgical block practical training at the Klinikum rechts der Isar, Technische
      Universitat of Munich (TUM), was changed from single grades of each day to a
      final objective structured clinical examination (OSCE). We report about the
      experiences in the past 12 months with this relatively new form of examination.
      METHODS: An OSCE was established as a practical exam with seven stations about
      suture techniques, internal fixation, first-aid education, hygiene and sterility,
      clinical examination and perioperative management. The feasibility of a
      comprehensive OSCE with the necessary modifications was studied and the grades
      had been compared. RESULTS: In the past 12 months four surgical block placements
      for over three weeks had been organised with a total of 326 students. 309
      students were admitted for the OSCE at the end of block practical training. The
      average score was 1.75. The medical student raters graded either equally or more
      stringently compared to the medical doctors. The transcript revealed in all OSCEs
      a normal distribution of grading with high validity. However, an adaptation of
      the evaluation forms and an extension of the stations with modified content was
      required to obtain the same test conditions for all students. The implementation
      of the OSCE on this scale is possible with adequate preparation time and
      sufficient financial support. The evaluation of the specimens after completion of
      the test were all positive. CONCLUSION: The new medical approval system calls for
      restructuring, not only in teaching but also in the form of examination of the
      courses. Through this practical test, those skills of a student will be assessed
      that cannot be tested by the IMPP exam. Moreover, this examination form provides
      an excellent preparation for the practical part of the oral state examination.
      This OSCE is even feasible with high numbers of students and offers with
      appropriate adaptation of the evaluation forms and test stations, a normal
      distribution of grading.

PMID- 22392263
TI  - Epidemiology and outcome of sepsis in a tertiary care PICU of Pakistan.
AB  - OBJECTIVE: To determine the epidemiology and outcome of sepsis in children
      admitted in pediatric intensive care unit (PICU) of a tertiary care hospital.
      METHODS: Retrospective review of children 1 mo to 14 y old, admitted to the PICU
      with severe sepsis or septic shock from January 2007 through December 2008 was
      done. Demographic, clinical and laboratory features of subjects were reviewed.
      The primary outcome was mortality at the time of discharge from PICU. The
      independent predictors of mortality were modeled using multiple logistic
      regression. RESULTS: In 2 years, 17.3% (133/767) children admitted to the PICU
      had sepsis. Median age was 18 mo (IQR 6-93 mo), with male: female ratio of 1.6:1.
      Mean PRISM III score was 9 (+/-7.8). One third had culture proven infection,
      majority (20%) having bloodstream infection. The frequency of multi-organ
      dysfunction syndrome (MODS) was 81% (108/133). The case specific mortality rate
      of sepsis was 24% (32/133). Multi-organ dysfunction (Adjusted OR 18.0, 95% CI 2.2
      144), prism score of >10 (Adjusted OR 1.5, 95% CI 0.6-4.0) and the need for > 2
      inotropes (Adjusted OR 3.5, 95% CI 1.3-9.2) were independently associated with
      mortality due to sepsis. CONCLUSIONS: The presence of septic shock and MODS is
      associated with high mortality in the PICU of developing countries.

PMID- 22392264
TI  - Disseminated cysticercosis in a child.

PMID- 22392265
TI  - Selective arterial embolization of giant renal tuberous sclerosis.
AB  - Different minimally invasive methods have been proposed to treat renal
      manifestation of tuberous sclerosis complex (TSC), in order to preserve kidney
      parenchyma and avoid nephrectomy. The case of a boy with bleeding giant
      angiomyolipoma treated by selective arterial embolization is discussed. The
      extensive renal lesions resulted significantly decreased, with resolution of
      arterial hypertension and abdominal symptoms. Differential renal function
      increased from 26.6% to 32.6%. Renal involvement in TSC requires careful
      parenchymal-sparing procedures. Selective embolization of the main renal lesions
      should be considered as first line therapy.

PMID- 22392266
TI  - Clinical profile of Langerhans Cell Histiocytosis at a tertiary centre: a
      prospective study.
AB  - OBJECTIVE: To study the varied presentations of Langerhans Cell Histiocytosis
      (LCH), the differential diagnosis of the varied presentations and the time lag in
      achieving the diagnosis. Prospective analysis of children diagnosed to have LCH
      over a period of 51 mo was done. A complete history and physical examination was
      undertaken in all patients, followed by relevant laboratory and radiological
      evaluation. Biopsy of the appropriate specimen was done. The extent of the
      disease was documented, accordingly treated and followed up. RESULTS: There were
      16 children with LCH from October 2005 through December 2009. The age ranged from
      8 mo to 72 mo. Diagnosis was confirmed by CD1a/S 100 in 15 children (93.75%). The
      mean time to arrive at the diagnosis was 9.9 mo. Multisystem disease was
      documented in 11 (68.75%) children and there were 4 (25.0%) cases of pulmonary
      LCH. The mean time of follow-up was 14.4 mo (range, 1 mo to 50.6 mo). Most common
      referral diagnoses in LCH patients was recurrent pneumonia and immunodeficiency.
      CONCLUSIONS: There is a need for high index of suspicion for diagnosis of LCH;
      misdiagnosis is frequent. Pulmonary involvement in children with LCH appears
      common. It is possibly still underdiagnosed. Nail changes are uncommon, but may
      act as a marker for multisystem disease. In addition to survival data and
      analysis of prognostic factors, the prospective collection of data on diverse
      presentations is essential, along with a high index of suspicion for the
      diagnosis of LCH.

PMID- 22392267
TI  - Treatment of chronic noninsertional Achilles tendinopathy with endoscopic
      Achilles tendon debridement and flexor hallucis longus transfer.
AB  - Decompression with debridement has been shown to be effective in pain management
      in patients with chronic mid-portion Achilles tendinopathy; however, augmentation
      with the flexor hallucis longus tendon can provide additional mechanical support.
      The technique of endoscopic debridement of the tendinopathic tendon together with
      flexor hallucis longus transfer is described to treat patients suffering from
      chronic painful noninsertional Achilles tendinopathy with the potential advantage
      of minimally invasive surgery. LEVELS OF EVIDENCE: Therapeutic, Level IV.

PMID- 22392268
TI  - Reducing the cost and frequency of explantations associated with single-level
      anterior diskectomy and fusion at a single institution through education.
AB  - STUDY DESIGN: We prospectively evaluated the costs/frequency of explanted
      instrumentation (devices implanted but removed prior to closure) for all single
      level anterior diskectomy (1-ADF) procedures performed in 2010 at a single
      institution before and after surgeon education. OBJECTIVE: To determine whether
      surgeon education would reduce the costs/frequency of explantation for 1-ADF.
      SUMMARY OF BACKGROUND DATA: In 2009, we reported that the cost of explanted
      devices was 9.2% of the cost of implanted devices. METHODS: The costs/frequencies
      of explantation for 1-ADF performed in 2010 at the same institution by the same
      surgeons were analyzed before and after surgeon education. From January through
      April, surgeons were unaware of concerns regarding explantation. At the end of
      April 2010, spinal surgeons were educated about explantation costs/frequency at 2
      meetings. Explantation costs/frequencies for the first 4 months of 2010 were
      compared with those for the last 8 months as well as with the results from 2009.
      RESULTS: Prior to surgeon education, instrumentation was explanted in 45.5% of
      the cases, whereas after education explantation occurred in 16% of the cases. The
      explantation rate (the number of explanted devices as a percentage of implanted
      devices) was lower after education for screws (12.5% vs. 7.7%), plates (9.4% vs.
      0%), and allograft spacers (7.1% vs. 2.9%), and lower than for rates from 2009.
      In 2010, the overall cost of explanted devices as a percentage of implanted
      devices was also lower after surgeon education (5.8%) than before surgeon
      education in 2010 (20.0%) or 2009 (9.2%). CONCLUSION: The frequency and cost of
      explanted instrumentation used to perform 1-ADF were reduced through surgeon
      education.

PMID- 22392270
TI  - Mitochondria in vascular disease.
AB  - Mitochondria are often regarded as the powerhouse of the cell by generating the
      ultimate energy transfer molecule, ATP, which is required for a multitude of
      cellular processes. However, the role of mitochondria goes beyond their capacity
      to create molecular fuel, to include the generation of reactive oxygen species,
      the regulation of calcium, and activation of cell death. Mitochondrial
      dysfunction is part of both normal and premature ageing, but can contribute to
      inflammation, cell senescence, and apoptosis. Cardiovascular disease, and in
      particular atherosclerosis, is characterized by DNA damage, inflammation, cell
      senescence, and apoptosis. Increasing evidence indicates that mitochondrial
      damage and dysfunction also occur in atherosclerosis and may contribute to the
      multiple pathological processes underlying the disease. This review summarizes
      the normal role of mitochondria, the causes and consequences of mitochondrial
      dysfunction, and the evidence for mitochondrial damage and dysfunction in
      vascular disease. Finally, we highlight areas of mitochondrial biology that may
      have therapeutic targets in vascular disease.

PMID- 22392271
TI  - Identification of two-histidines one-carboxylate binding motifs in proteins
      amenable to facial coordination to metals.
AB  - Among natural metalloenzymes, the facial two-histidines one-carboxylate binding
      motif (FTM) is a widely represented first coordination sphere motif present in
      the active site of a variety of metalloenzymes. A PDB search revealed a total of
      1685 structures bearing such FTMs bound to a metal. Sixty statistically
      representative FTMs were selected and used as template for the identification of
      structurally characterized proteins bearing these three amino acids in a
      propitious environment for binding to a transition metal. This geometrical
      superposition search, carried out using the STAMPS software, returned 2320 hits.
      While most consisted of either apo-FTMs or bore strong sequence homology to known
      FTMs, seven such structures lying within a cavity were identified as novel and
      viable scaffolds for the creation of artificial metalloenzymes bearing an FTM.

PMID- 22392272
TI  - Stability and sustained oscillations in a ventricular cardiomyocyte model.
AB  - The Luo-Rudy I model, describing the electrophysiology of a ventricular
      cardiomyocyte, is associated with an 8-dimensional discontinuous dynamical system
      with logarithmic and exponential non-linearities depending on 15 parameters. The
      associated stationary problem was reduced to a nonlinear system in only two
      unknowns, the transmembrane potential V and the intracellular calcium
      concentration [Ca]( i ). By numerical approaches appropriate to bifurcation
      problems, sections in the static bifurcation diagram were determined. For a
      variable steady depolarizing or hyperpolarizing current (I (st)), the
      corresponding projection of the static bifurcation diagram in the (I (st), V)
      plane is complex, featuring three branches of stationary solutions joined by two
      limit points. On the upper branch oscillations can occur, being either damped at
      a stable focus or diverted to the lower branch of stable stationary solutions
      when reaching the unstable manifold of a homoclinic saddle, thus resulting in
      early after-depolarizations (EADs). The middle branch of solutions is a series of
      unstable saddle points, while the lower one a series of stable nodes. For
      variable slow inward and K(+) current maximal conductances (g (si) and g (K)), in
      a range between 0 and 4-fold normal values, the dynamics is even more complex,
      and in certain instances sustained oscillations tending to a limit cycle appear.
      All these types of behavior were correctly predicted by linear stability analysis
      and bifurcation theory methods, leading to identification of Hopf bifurcation
      points, limit points of cycles and period doubling bifurcations. In particular
      settings, e.g. one-fifth-of-normal g (si), EADs and sustained high amplitude
      oscillations due to an unstable resting state may occur simultaneously.

PMID- 22392273
TI  - A fast algorithm for treating dielectric discontinuities in charged spherical
      colloids.
AB  - Electrostatic interactions between multiple colloids in ionic fluids are
      attracting much attention in studies of biological and soft matter systems. The
      evaluation of the polarization surface charges due to the spherical dielectric
      discontinuities poses a challenging problem to highly efficient computer
      simulations. In this paper, we propose a new method for fast calculating the
      electric field of spaced spheres using the multiple reflection expansion. The
      method uses a technique of recursive reflections among the spherical interfaces
      based on a formula of the multiple image representation, resulting in a simple,
      accurate and close-form expression of the surface polarization charges. Numerical
      calculations of the electric potential energies of charged spheres demonstrate
      the method is highly accurate with small number of reflections, and thus
      attractive for the use in practical simulations of related problems such as
      colloid suspension and macromolecular interactions.

PMID- 22392274
TI  - Critical evaluation of quantitative colocalization analysis in confocal
      fluorescence microscopy.
AB  - Spatial colocalization of fluorescently labeled proteins can reveal valuable
      information about proteinprotein interactions. Compared to qualitative visual
      interpretation of dual color images, quantitative colocalization analysis (QCA)
      provides more objective evaluations to the degree of colocalization. However, the
      finite resolution power of microscopes and the spatial patterns of intracellular
      structures may compromise the reliability of many classical QCA methods. In this
      paper, we discuss the strength and weakness of some mostly used QCA methods. By
      studying their applications on computer-simulated images and biological images,
      we show that classical pixel intensity based QCA methods are often vulnerable to
      coincidental overlapping among resolution elements (resel) distributions and thus
      not suitable to images with high molecular density or with low resolution. Also,
      many QCA methods can mistakenly regard long range correlation as colocalization
      due to protein localization in intracellular structures. The newly developed
      protein-protein index (PPI) approach is able to reduce the influence from resel
      overlapping and spatial intracellular pattern compared to previous methods,
      significantly improving the reliability of QCA.

PMID- 22392275
TI  - Computer aided subunit vaccine design against pathogenic Leptospira serovars.
AB  - Epitopes of Leptospira inducing CD4(+) T-cell responses by binding to human MHC
      molecules could critically contribute to the development of subunit vaccines for
      leptospirosis. Herein, we have identified unique vaccine peptides from outer
      membrane proteins (OMPs) common to four sequenced pathogenic Leptospira serovars
      through in silico reverse vaccinology technique. The OMPs were explored for
      probable antigens using jemboss and screened in ProPred subsequently to predict
      thirty HLA-DRB epitopes. The HLA-DRB epitopes were validated through published
      positive control (HA307-PKYVKQNTLKLAT-319), SYFPEITHI and immune epitope database
      (IEDB) to list twelve epitopes as putative subunit vaccine peptides from nine
      OMPs. Cation efflux system membrane protein (czcA) having four subunit vaccine
      peptides, was modeled in Modeller9v7 and evaluated through Procheck, ProSA and
      ProQ. The HLA-DRB alleles and czcA 3D interactions were studied using Hex 5.1.
      Further, the T-cell epitopes present in czcA were docked individually with HLA
      DRB alleles. The docking result revealed that czcA and its epitopes were
      interacting well with HLA-DRB alleles, hence would certainly produce cell
      mediated immune response in host. Thus, czcA and its four subunit vaccine
      peptides would be ideal T-cell driven efficacious vaccine against leptospirosis.

PMID- 22392276
TI  - Predicting Km values of beta-glucosidases using cellobiose as substrate.
AB  - The Michaelis-Menten constant Km is a very important parameter to relate enzyme
      with its substrate in enzymatic reaction. Although Km can be experimentally
      determined, the Km values are not easily available in literature. With rapid
      increase of newly designed enzymes, we face the shortage of parameters related to
      enzymatic reactions. The beta-glucosidase is a crucial enzyme for cellulose
      hydrolysis and cellobiose is one of its substrates. In this study, we attempt to
      develop models to predict Km with cellobiose as substrates using information
      about primary structure of beta-glucosidase. The results show that the 20-1
      feedforward backpropagation neural network using the amino-acid distribution
      probability as predictor works best for prediction of Km values.

PMID- 22392277
TI  - Predictions on impact of missense mutations on structure function relationship of
      PAX6 and its alternatively spliced isoform PAX6(5a).
AB  - The PAX6 contains two DNA-binding domains, paired domain (PD), homeodomain (HD),
      and a transactivation domain (TD). Only the crystal structure of PD and the
      solution structure of HD of PAX6 are known. Mutations in PAX6 show variable
      penetrance, and expressivity of ocular and neural diseases, but the mechanism is
      poorly understood. Its alternatively spliced isoform PAX6(5a), is also required
      in a specific ratio for optimal functions. To understand impact of missense
      mutations on stability, and conformation of PAX6, whose functional analyses are
      described in PAX6 allelic variant database, were considered. Representative
      mutations like PAX6-L46R, -C52R, -V126D, -R128C, -R242T, -P375Q, -Q422R, -V256E,
      and -S259P from PD, HD, and TD of PAX6 were explored. The secondary structures
      were analyzed through PSIPRED, and relative solvent accessibilities (RSA) of the
      mutant and the wild type amino acid residues were compared through SABLE. The
      change in the contact residues and calculations of energy level were studied
      through SVMcon, MUpro, and FoldX, respectively. The 3D modeling was performed
      with the help of MODELLER and models were visualized in Chimera. Predictions
      suggest mutation induced alterations in local conformation or misfolding in DNA
      binding domains of PAX6 and PAX6(5a). The predicted impact of mutations via
      secondary structure, changes in free energy, stability, conformation, and
      experimental reports on DNA-binding and transactivation, necessarily provides a
      strong background to explain structure-function relationship of PAX6 and
      PAX6(5a). However, because of their predictive nature, these findings need to be
      validated with other experimental evidences when structure of full length PAX6 is
      available.

PMID- 22392278
TI  - Preliminary analysis to target pyruvate phosphate dikinase from wolbachia
      endosymbiont of Brugia malayi for designing anti-filarial agents.
AB  - Filariasis causing nematode Brugia malayi is shown to harbor wolbachia bacteria
      as symbionts. The sequenced genome of the wolbachia endosymbiont from B.malayi
      (wBm) offers an unprecedented opportunity to identify new wolbachia drug targets.
      Genome analysis of the glycolytic/gluconeogenic pathway has revealed that wBm
      lacks pyruvate kinase (PK) and may instead utilize the enzyme pyruvate phosphate
      dikinase (PPDK; ATP: pyruvate, orthophosphate phosphotransferase, EC 2.7.9.1).
      PPDK catalyses the reversible conversion of AMP, PPi and phosphoenolpyruvate into
      ATP, Pi and pyruvate. Most organisms including mammals exclusively possess PK.
      Therefore the absence of PPDK in mammals makes this enzyme as attractive
      wolbachia drug target. In the present study we have modeled the three dimensional
      structure of wBm PPDK. The template with 50% identity and 67% similarity in amino
      acid sequence was employed for homology-modeling approach. The putative active
      site consists of His476, Arg360, Glu358, Asp344, Arg112, Lys43 and Glu346 was
      selected as site of interest for designing suitable inhibitor molecules. Docking
      studies were carried out using induced fit algorithms with OPLS force field of
      Schrodinger's Glide. The lead molecules which inhibit the PPDK activity are taken
      from the small molecule library (Pubchem database) and the interaction analysis
      showed that these compounds may inhibit the function of PPDK in wBm.

PMID- 22392279
TI  - Arabidopsis WRKY33 is a key transcriptional regulator of hormonal and metabolic
      responses toward Botrytis cinerea infection.
AB  - The Arabidopsis (Arabidopsis thaliana) transcription factor WRKY33 is essential
      for defense toward the necrotrophic fungus Botrytis cinerea. Here, we aimed at
      identifying early transcriptional responses mediated by WRKY33. Global expression
      profiling on susceptible wrky33 and resistant wild-type plants uncovered massive
      differential transcriptional reprogramming upon B. cinerea infection. Subsequent
      detailed kinetic analyses revealed that loss of WRKY33 function results in
      inappropriate activation of the salicylic acid (SA)-related host response and
      elevated SA levels post infection and in the down-regulation of jasmonic acid
      (JA)-associated responses at later stages. This down-regulation appears to
      involve direct activation of several jasmonate ZIM-domain genes, encoding
      repressors of the JA-response pathway, by loss of WRKY33 function and by
      additional SA-dependent WRKY factors. Moreover, genes involved in redox
      homeostasis, SA signaling, ethylene-JA-mediated cross-communication, and
      camalexin biosynthesis were identified as direct targets of WRKY33. Genetic
      studies indicate that although SA-mediated repression of the JA pathway may
      contribute to the susceptibility of wrky33 plants to B. cinerea, it is
      insufficient for WRKY33-mediated resistance. Thus, WRKY33 apparently directly
      targets other still unidentified components that are also critical for
      establishing full resistance toward this necrotroph.

PMID- 22392281
TI  - Selective synthesis of organogold magic clusters Au54(C=CPh)26.
AB  - Organogold clusters Au(54)(C(2)Ph)(26) were selectively synthesized by reacting
      polymer-stabilized Au clusters (1.2 +/- 0.2 nm) with excess phenylacetylene in
      chloroform.

PMID- 22392280
TI  - Cooperative function of PLDdelta and PLDalpha1 in abscisic acid-induced stomatal
      closure in Arabidopsis.
AB  - Phospholipase D (PLD) is involved in responses to abiotic stress and abscisic
      acid (ABA) signaling. To investigate the roles of two Arabidopsis (Arabidopsis
      thaliana) PLDs, PLDalpha1 and PLDdelta, in ABA signaling in guard cells, we
      analyzed ABA responses in guard cells using Arabidopsis wild type, pldalpha1 and
      plddelta single mutants, and a pldalpha1 plddelta double mutant. ABA-induced
      stomatal closure was suppressed in the pldalpha1 plddelta double mutant but not
      in the pld single mutants. The pldalpha1 and plddelta mutations reduced ABA
      induced phosphatidic acid production in epidermal tissues. Expression of either
      PLDalpha1 or PLDdelta complemented the double mutant stomatal phenotype. ABA
      induced stomatal closure in both pldalpha1 and plddelta single mutants was
      inhibited by a PLD inhibitor (1-butanol ), suggesting that both PLDalpha1 and
      PLDdelta function in ABA-induced stomatal closure. During ABA-induced stomatal
      closure, wild-type guard cells accumulate reactive oxygen species and nitric
      oxide and undergo cytosolic alkalization, but these changes are reduced in guard
      cells of the pldalpha1 plddelta double mutant. Inward-rectifying K(+) channel
      currents of guard cells were inhibited by ABA in the wild type but not in the
      pldalpha1 plddelta double mutant. ABA inhibited stomatal opening in the wild type
      and the plddelta mutant but not in the pldalpha1 mutant. In wild-type rosette
      leaves, ABA significantly increased PLDdelta transcript levels but did not change
      PLDalpha1 transcript levels. Furthermore, the pldalpha1 and plddelta mutations
      mitigated ABA inhibition of seed germination. These results suggest that
      PLDalpha1 and PLDdelta cooperate in ABA signaling in guard cells but that their
      functions do not completely overlap.

PMID- 22392282
TI  - Plasmid pP62BP1 isolated from an Arctic Psychrobacter sp. strain carries two
      highly homologous type II restriction-modification systems and a putative organic
      sulfate metabolism operon.
AB  - The complete nucleotide sequence of plasmid pP62BP1 (34,467 bp), isolated from
      Arctic Psychrobacter sp. DAB_AL62B, was determined and annotated. The conserved
      plasmid backbone is composed of several genetic modules, including a replication
      system (REP) with similarities to the REP region of the iteron-containing plasmid
      pPS10 of Pseudomonas syringae. The additional genetic load of pP62BP1 includes
      two highly related type II restriction-modification systems and a set of genes
      (slfRCHSL) encoding enzymes engaged in the metabolism of organic sulfates, plus a
      putative transcriptional regulator (SlfR) of the AraC family. The pP62BP1 slf
      locus has a compact and unique structure. It is predicted that the enzymes SlfC,
      SlfH, SlfS and SlfL carry out a chain of reactions leading to the transformation
      of alkyl sulfates into acyl-CoA, with dodecyl sulfate (SDS) as a possible
      starting substrate. Comparative analysis of the nucleotide sequences of pP62BP1
      and other Psychrobacter spp. plasmids revealed their structural diversity.
      However, the presence of a few highly conserved DNA segments in pP62BP1, plasmid
      1 of P. cryohalolentis K5 and pRWF-101 of Psychrobacter sp. PRwf-1 is indicative
      of recombinational shuffling of genetic information, and is evidence of lateral
      gene transfer in the Arctic environment.

PMID- 22392283
TI  - Effect of C-terminal truncation on enzyme properties of recombinant
      amylopullulanase from Thermoanaerobacter pseudoethanolicus.
AB  - The smallest and enzymatically active molecule, TetApuQ818, was localized within
      the C-terminal Q818 amino acid residue after serial C-terminal truncation
      analysis of the recombinant amylopullulanase molecule (TetApuM955) from
      Thermoanaerobacter pseudoethanolicus. Kinetic analyses indicated that the overall
      catalytic efficiency, k (cat)/K (m), of TetApuQ818 was 8-32% decreased for the
      pullulan and the soluble starch substrate, respectively. Changes to the substrate
      affinity, K (m), and the turnover rate, k (cat), were decreased significantly in
      both enzymatic activities of TetApuQ818. TetApuQ818 exhibited less
      thermostability than TetApuM955 when the temperature was raised above 85 degrees
      C, but it had similar substrate-binding ability and hydrolysis products toward
      various substrates as TetApuM955 did. Both enzymes showed similar spectroscopies
      of fluorescence and circular dichroism, suggesting the active folding
      conformation was maintained after this C-terminal Q818 deletion. This study
      suggested that the binding ability of insoluble starch by TetApuM955 did not rely
      on the putative C-terminal carbohydrate binding module family 20 (CBM20) and two
      FnIII regions of TetApu, though the integrity of the AamyC module of TetApuQ818
      was required for the enzyme activity.

PMID- 22392284
TI  - Diverse action of acrylamide on cytochrome P450 and glutathione S-transferase
      isozyme activities, mRNA levels and protein levels in human hepatocarcinoma
      cells.
AB  - Humans are exposed to acrylamide in their diet and cigarette smoke. Acrylamide is
      metabolized into glycidamide by CYP2E1. However, very few studies regarding the
      effects of acrylamide on cytochrome P450 and Glutathione S-Transferase (GST)
      isozymes have been pursued. The aim of this study is to elucidate the effects of
      acrylamide on cytochrome P450 and GST isozymes in HepG2 cell line. Treatment with
      1.25 and 2.5 mM acrylamide caused 9.5- and 3.7-fold increases and 4.0- and 3.3
      fold increases in CYP1A-associated ethoxyresorufin O-deethylase (EROD) and
      methoxyresorufin O-demethylase (MROD) activities, respectively. These increases
      were consistent with increases in mRNA and protein levels of these isozymes.
      Similarly, CYP2E1-associated aniline 4-hydroxylase (ANH) activity, protein
      levels, and mRNA levels increased 2.1- and 2.6-fold, 2.4- and 3.2-fold, and 1.4-
      and 1.9-fold following 1.25 and 2.5 mM acrylamide treatments, respectively. In
      addition, GST-mu activity was increased 2.4- and 5.1-fold by acrylamide.
      Moreover, GST-mu mRNA and protein levels increased twofold as a result of
      acrylamide treatment. In contrast, GST-pi protein and mRNA levels decreased
      significantly. In conclusion, human cell exposure to acrylamide causes an
      increase in the levels of carcinogenicity and toxicity and a disturbance in drug
      metabolism, possibly due to complex effects on P450 and GST isozymes.

PMID- 22392285
TI  - Progress, challenges and prospects of eco-hydrological studies in the Tarim river
      basin of Xinjiang, China.
AB  - Eco-hydrological research in arid inland river basins has been a focus of
      geologists and ecologists as it is crucial for maintaining the sustainable
      development of socio-economy, particularly in ecologically vulnerable areas.
      Based on the research work carried out in the Tarim River basin of Xinjiang,
      northwestern China, this paper summarizes synthetically the climate change and
      associated responses of water resources in the mountainous area, land use and
      land cover in the oasis, and plants responding to environmental stresses in the
      desert area of the river basin. Research gaps, challenges, and future
      perspectives in the eco-hydrological studies of the Tarim River basin are also
      discussed.

PMID- 22392286
TI  - Wildland-urban interface fires and socioeconomic conditions: a case study of a
      northwestern Patagonia city.
AB  - In many regions of the world, fires are primarily of anthropogenic origin. In
      northwestern Patagonia, the number of fires is not correlated with meteorological
      variables, but is concentrated in urban areas. This study was conducted in the
      wildland-urban interface (WUI) area of San Carlos de Bariloche (Patagonia,
      Argentina), within the Nahuel Huapi National Park. WUI fires are particularly
      problematic because, besides people and goods, they represent a danger to
      protected areas. We studied the relationship between fire records and
      socioeconomic indicators within the WUI of San Carlos de Bariloche. We conducted
      a Multiple Correspondence Factorial Analysis and an Ascendant Hierarchical
      Classification of the city neighborhoods. The results show that the neighborhoods
      in Bariloche can be divided into three classes: High Socioeconomic Fire Risk
      neighborhoods, including neighborhoods with the highest fire rates, where people
      have low instruction level, high levels of unsatisfied basic needs and high
      unemployment levels; Low Socioeconomic Fire Risk neighborhoods, that groups
      neighborhoods which present the opposite characterization, and Moderate
      Socioeconomic Fire Risk neighborhoods, which are more heterogeneous. Once
      neighborhoods were classified, a Socioeconomic Fire Risk map was generated,
      supplementing the existing WUI Fire Danger map. Our results emphasize the
      relevance of socioeconomic variables to fire policies.

PMID- 22392287
TI  - Neighborhood-level socioeconomic determinants impact outcomes in nonsmall cell
      lung cancer patients in the Southeastern United States.
AB  - BACKGROUND: Studies examining the impact of lower socioeconomic status (SES) on
      the outcomes of patients with nonsmall cell lung cancer (NSCLC) are inconsistent.
      The objective of this study was to clearly elucidate the association between SES,
      education, and clinical outcomes among patients with NSCLC. METHODS: The study
      population was derived from a consecutive, retrospective cohort of patients with
      NSCLC who received treatment within the Duke Health System between 1995 and 2007.
      SES determinants were based on the individual's census tract and corresponding
      2000 Census data. Determinants included the percentage of the population living
      below poverty, the median household income, and the percentages of residents with
      at least a high school diploma and at least a bachelor's degree. The SES and
      educational variables were divided into quartiles. Statistical comparisons were
      performed using the 25th and 75th percentiles. RESULTS: Individuals who resided
      in areas with a low median household income or in which a high percentage of
      residents were living below the poverty line had a shorter cancer-specific 6-year
      survival than individuals who resided in converse areas (P = .0167 and P = .0067,
      respectively). Those living in areas in which a higher percentage of residents
      achieved a high school diploma had improved disease outcomes compared with those
      living in areas in which a lower percentage attained a high school diploma (P =
      .0033). A survival advantage also was observed for inhabitants of areas in which
      a higher percentage of residents attained a bachelor's degree (P = .0455).
      CONCLUSIONS: Low SES was identified as an independent prognostic factor for poor
      survival in patients with both early and advanced stage NSCLC. Patients who lived
      in areas with high poverty levels, low median incomes, and low education levels
      had worse mortality.

PMID- 22392288
TI  - Therapy: localized gastric cancer--a CLASSIC shift in the paradigm?

PMID- 22392290
TI  - The enteric nervous system and neurogastroenterology.
AB  - Neurogastroenterology is defined as neurology of the gastrointestinal tract,
      liver, gallbladder and pancreas and encompasses control of digestion through the
      enteric nervous system (ENS), the central nervous system (CNS) and integrative
      centers in sympathetic ganglia. This Review provides a broad overview of the
      field of neurogastroenterology, with a focus on the roles of the ENS in the
      control of the musculature of the gastrointestinal tract and transmucosal fluid
      movement. Digestion is controlled through the integration of multiple signals
      from the ENS and CNS; neural signals also pass between distinct gut regions to
      coordinate digestive activity. Moreover, neural and endocrine control of
      digestion is closely coordinated. Interestingly, the extent to which the ENS or
      CNS controls digestion differs considerably along the digestive tract. The
      importance of the ENS is emphasized by the life-threatening effects of certain
      ENS neuropathies, including Hirschsprung disease and Chagas disease. Other ENS
      disorders, such as esophageal achalasia and gastroparesis, cause varying degrees
      of dysfunction. The neurons in enteric reflex pathways use a wide range of
      chemical messengers that signal through an even wider range of receptors. These
      receptors provide many actual and potential targets for modifying digestive
      function.

PMID- 22392292
TI  - Liver: determining prognosis in acute liver failure.

PMID- 22392293
TI  - Liver transplantation: outcomes could be improved in HCV-HIV co-infected liver
      transplant recipients.

PMID- 22392295
TI  - Colonoscopy: diagnostic yield of flexible sigmoidoscopy and CTC.

PMID- 22392298
TI  - Pediatrics: tailoring weight-control programs to teenagers.

PMID- 22392303
TI  - [Introduction on why your data is important].

PMID- 22392299
TI  - Intraductal papillary mucinous neoplasms of the pancreas--a surgical disease.
AB  - Cystic pancreatic neoplasms are increasingly recognized, with intraductal
      papillary mucinous neoplasms of the pancreas (IPMNs) being the most frequently
      observed type. IPMNs are characterized by mucin production and epithelial growth
      within the pancreatic ducts, and are generally differentiated according to
      location: main pancreatic duct, its major side branches, or both (mixed type).
      IPMNs vary from benign to malignant and are considered precursor lesions of
      pancreatic adenocarcinoma. However, the exact time to neoplastic transformation
      and whether all IPMNs progress to malignant tumors is unclear. Surgical resection
      is warranted for all main-duct and mixed-type IPMNs (they harbor a high risk of
      malignancy of ~70%). By contrast, branch-duct IPMNs progress to cancer in only
      ~30% of cases. Thus, according to current guidelines (Sendai criteria),
      asymptomatic side-branch IPMNs <3 cm in size without suspicious radiological
      features (such as size progression) can be treated conservatively. Lately, even
      this approach has become controversial, owing to a number of Sendai-negative
      IPMNs showing malignant transformation. Although most IPMNs should be resected by
      standard oncological procedures (including lymphadenectomy), small Sendai
      negative IPMNs can be treated with limited resections. This Review summarizes
      current knowledge of the treatment of IPMNs, with a particular focus on surgical
      approaches to this disease.

PMID- 22392304
TI  - [Clinical research as a strategy for health development].

PMID- 22392305
TI  - [Professional-patient relationship and bioethics: a discussion always current].

PMID- 22392306
TI  - ["SIC"].

PMID- 22392307
TI  - [Is EEG with brain mapping superior to traditional EEG in the diagnosis of
      neurological disorders?].

PMID- 22392308
TI  - [Does nesiritide reduce dyspnea in decompensated heart failure?].

PMID- 22392309
TI  - [Cocaine-induced ischemic colitis].

PMID- 22392310
TI  - [Tuberculosis of the hip joint: apropos of a case].

PMID- 22392313
TI  - Evaluation of CA-125 and soluble CD-23 in patients with pelvic endometriosis: a
      case-control study.
AB  - OBJECTIVE: To evaluate serum concentrations of CA-125 and soluble CD-23 and to
      correlate them with clinical symptoms, localization and stage of pelvic
      endometriosis and histological classification of the disease. METHODS: Blood
      samples were collected from 44 women with endometriosis and 58 without
      endometriosis, during the first three days (1st sample) and during the 7th, 8th
      and 9th day (2nd sample) of the menstrual cycle. Measurements of CA-125 and
      soluble CD-23 were performed by ELISA. Mann-Whitney U test was used for age, pain
      evaluations (visual analog scale) and biomarkers concentrations. RESULTS: Serum
      levels of CA125 were higher in endometriosis patients when compared to the
      control group during both periods of the menstrual cycle evaluated in the study.
      This marker was also elevated in women with chronic pelvic pain, deep dyspareunia
      (2nd sample), dysmenorrhea (both samples) and painful defecation during the
      menstrual flow (2nd sample). CA-125 concentration was higher in advanced stages
      of the disease in both samples and also in women with ovarian endometrioma.
      Concerning CD-23, no statistically significant differences were observed between
      groups. CONCLUSION: The concentrations of CA-125 were higher in patients with
      endometriosis than in patients without the disease. No significantly differences
      were observed for soluble CD-23 levels between groups.

PMID- 22392311
TI  - [Gastroesophageal reflux disease: non-pharmacological treatment].

PMID- 22392314
TI  - [Total energy value and percentage contribution of calories from macronutrients
      in the diet of elderly individuals from Fortaleza, state of Ceara, Brazil].
AB  - OBJECTIVE: Describe the total energy value and percentage contribution of
      calories from macronutrients in the diet of elderly individuals living in
      Fortaleza/CE. METHODS: This is a population-based, cross-sectional domiciliary
      study, which included 458 elderly individuals (66.6% women). The variables
      evaluated were total energy value (TEV) and the percentage contribution of
      calories from proteins, carbohydrates, and lipids. The results are shown as mean,
      standard deviation, and percentile distribution (P5, P10, P25, P50, P75, P90,
      P95). The Student's t-test and analysis of variance (one-way ANOVA) with LSD post
      hoc tests were used to determine the statistical significance of means between
      two groups and among three or more groups, respectively. RESULTS: When comparing
      the mean values of TEV among categories of socioeconomic and demographic
      variables, statistically significant differences were found between women for
      ethnicity, years of schooling and socioeconomic level. Among men, differences
      were found for years of schooling and socioeconomic level. The mean energy value
      of men's diet was significantly higher than that of women (1475.8 kcal and 1236.4
      kcal, respectively). The mean values of calorie percentage contribution from
      proteins, carbohydrates, and lipids were similar between men and women.
      CONCLUSION: The elderly of this study showed significant differences in mean
      values of TEV between sexes and between the categories years of schooling and
      socioeconomic level. Women also showed significant differences between the ethnic
      categories. The mean relative contribution of macronutrients in TEV was similar
      between genders and age groups.

PMID- 22392315
TI  - [Left and right ventricular hypertrophy at autopsy of hypertensive individuals].
AB  - OBJECTIVE: To measure the right and left ventricular thickness in deceased
      individuals with a history of hypertension submitted to clinical autopsies.
      METHODS: We selected 90 cases from the Death Verification Service of the city of
      Recife, state of Pernambuco, Brazil, of both sexes, with a history of essential
      arterial hypertension related to heart wall thickness, in addition to correlation
      with autopsy findings and other clinical reports. RESULTS: There was a
      significant association between the presence of left ventricular hypertrophy
      (LVH) and right ventricular hypertrophy (RVH) and between severe hypertensive
      cardiomyopathy and RVH. There was a predominance of RVH and LVH in men aged 60-79
      years and a higher prevalence in the Brazilian mulatto and Black ethnic groups
      and in those with adequate nutritional status or overweight and obese
      individuals. CONCLUSION: It was observed that the presence of RVH was related to
      LVH, suggesting that there are similar pathogenic factors involved in the
      development of bilateral hypertrophy. The RVH seems to be associated with more
      severe heart disease and may, based on other studies, be considered as a new
      prognostic factor in the evaluation of hypertensive patients.

PMID- 22392316
TI  - [Sexual and reproductive rights in adolescence].
AB  - OBJECTIVE: To present legal milestones to ensure the Brazilian adolescent
      autonomy indealing with their sexual and reproductive health. METHODS: Literature
      review of national legislation published on the official sites of governmental
      organs (Ministry of Health and Ministry of Education) and Class Associations
      (Federal Council of Medicine [Conselho Federal de Medicina--CFM] and the Federal
      Council of Nursing--COFEN). RESULTS: We found 8 legislations, of which 3 were
      from Class Associations (COFEN and CFM), one Interministerial Ordinance
      (Ministries of Health and Education), one Technical Note of the National STD/AIDS
      Program, and 3 Federal Laws. Many of the legal guarantees directly affect the
      adolescent population (guarantee of schooling during pregnancy and puerperal
      period or maternity leave, condom distribution, no discrimination in the school
      environment on the basis of serology). They are important tools for the
      preservation of sexual and reproductive rights, privacy of medical care, search
      for reliable health information, and access to inputs such as condoms and
      contraceptive methods. CONCLUSION: The analysis of the legislation listed in the
      present study demonstrated that these legal milestones are essential to ensure
      the safe and healthy experience of sexuality, and all health and education
      professionals involved in adolescent counseling should know them comprehensively.

PMID- 22392317
TI  - [Depressive symptoms among medical intern students in a Brazilian public
      university].
AB  - OBJECTIVE: To estimate, among Medical School intern students, the prevalence of
      depressive symptoms and their severity, as well as associated factors. METHODS:
      Cross-sectional study in May 2008, with a representative sample of medical intern
      students (n = 84) from Universidade Federal de Sergipe (UFS). Beck Depression
      Inventory (BDI) and a structured questionnaire containing information on
      sociodemographic variables, teaching-learning process, and personal aspects were
      used. The exploratory data analysis was performed by descriptive and inferential
      statistics. Finally, the analysis of multiple variables by logistic regression
      and the calculation of simple and adjusted ORs with their respective 95%
      confidence intervals were performed. RESULTS: The general prevalence was 40.5%,
      with 1.2% (95% CI: 0.0-6.5) of severe depressive symptoms; 4.8% (95% CI: 1.3
      11.7) of moderate depressive symptoms; and 34.5% (95% CI: 24.5-45.7) of mild
      depressive symptoms. The logistic regression revealed the variables with a major
      impact associated with the emergence of depressive symptoms: thoughts of dropping
      out (OR 6.24; p = 0.002); emotional stress (OR 7.43;p = 0.0004); and average
      academic performance (OR 4.74; p = 0.0001). CONCLUSION: The high prevalence of
      depressive symptoms in the study population was associated with variables related
      to the teaching-learning process and personal aspects, suggesting immediate
      preemptive measures regarding Medical School graduation and student care are
      required.

PMID- 22392318
TI  - [Prevalence and factors associated with metabolic syndrome in users of primary
      healthcare units in Sao Paulo--SP, Brazil].
AB  - OBJECTIVE: To determine the relationship between metabolic syndrome (MS) and
      socioeconomic level, life style, health status, family history of morbidity, and
      residence areas. METHODS: This is a cross-sectional cohort study. The random
      sample consisted of users of two primary health care units (Unidades Basicas de
      Saude--UBSs) in the city of Sao Paulo--Jardim Comercial (UBS1), and Jardim
      Germania (UBS2), a total of 452 subjects. The NCEP ATP IIIcriterion was used to
      diagnose MS. Weight, height, abdominal and hip circumferences were measured for
      the anthropometric evaluation. A general questionnaire was used to obtain
      sociodemographic and socioeconomic data; family history; medical history;
      behavioral habits such as smoking, drinking, and physical activity. Multivariate
      logistic regression was used to establish the association between explanatory
      variables of interest and MS. RESULTS: At UBS1, MS percentage was 56.1%; at UBS2,
      34.0%. There was a direct and significant association between MS and age, female
      gender, race, smoking, drinking, physical activity level, stress, and family
      history of heart disease and diabetes mellitus. Education level showed an inverse
      association. Subjects living in a lower socioeconomic level neighborhood had a
      higher MS risk. CONCLUSION: The results suggest that the morbidities that compose
      MS are a serious publichealth problem in that population.

PMID- 22392319
TI  - What should we know about metabolic syndrome and lipodystrophy in AIDS?
AB  - OBJECTIVE: Prevalence of chronic complications of HIV infection is increasing and
      early recognition and treatment of the components of metabolic syndrome (MS) are
      essential to prevent cardiovascular and metabolic complications. Considering
      this, we performed a cross-sectional study on the prevalence and risk-factors for
      MS among HIV-infected subjects. METHODS: A total of 819 patients followed at a
      large outpatient HIV unit were assessed by an interviewer-administered
      questionnaire that recorded several demographic, epidemiologic, clinical,
      laboratory, and social variables. Lipodystrophy diagnosis relied on agreement
      between patient's self-report and physician's observation of altered body-fat
      deposits. The presence of three or more of the following characteristics
      identified MS: increased waist circumference, hypertriglyceridemia, low HDL
      cholesterol level, hypertension, and hyperglycemia. We used logistic regression
      analyses to study variables independently associated with MS. RESULTS: The
      prevalence of MS was 20.6% and that of lipodystrophy was 38.5%. 61 (36.1%) out of
      169 patients with MS had also lipodystrophy. Patients with metabolic syndrome
      were significantly more likely to be older (OR = 1.08), had higher CD4 counts (OR
      = 1.001), had an increased body mass index (OR = 1.27) and had longer exposure to
      antiretroviral therapy (OR = 1.01) than those without metabolic syndrome.
      CONCLUSION: Both traditional risk factors for cardiovascular disease and factors
      associated with HIV infection itself, such as an increased CD4 cell count and a
      longer exposure to antiretroviral therapy, seem to be associated with metabolic
      syndrome in the present study population.

PMID- 22392320
TI  - [Comparative analysis of injuries observed in motorcycle riders involved in
      traffic accidents and victims of other blunt trauma mechanisms].
AB  - OBJECTIVE: To conduct a comparative analysis of the lesions found among
      motorcycle riders involved in traffic accidents and victims of other mechanisms
      of blunt trauma. METHODS: Analysis of data prospectively collected on protocols
      for trauma patients older than 13 years, admitted from 06/10/2008 to 09/01/2009,
      victims of blunt trauma. Data collected included trauma mechanism, vital signs at
      admission, laboratory tests, injuries, and treatment.Stratification of trauma and
      lesion severity was performed by calculating the trauma index: Glasgow Coma Scale
      (GCS), Revised Trauma Score (RTS), Abbreviated Injury Scale (AIS), Injury
      Severity Score (ISS) and TRISS. We compared the variables between motorcycle
      riders (group A) and the others (group B). Severe injuries were considered when
      AIS > 3. For statistical analysis, we used Student's t, Mann Whitney, chi-square
      and Fisher's test, with p < 0.05 considered statistically significant. RESULTS:
      The study included 3,783 blunt trauma victims, aged 14 to 99 years, of which
      76.0% were males. The most frequent trauma mechanisms were accidents involving
      motorcycle riders (24.4%) and pedestrians (22.6%). When comparing the variables
      between groups A and B, we observed that motorcycle riders were significantly (p
      < 0.05) younger (28.9 +/- 8.5 years vs. 42.4 +/- 18.5 years) and had lower mean
      AIS in the head segment (0.3 +/- 0.9 vs. 0.8 +/- 1.1), as well as higher mean GCS
      at admission (14.5 +/- 1.9 vs. 14.2 +/- 2.2), AIS in the extremities (1.5 +/- 1.2
      vs. 0.9 +/- 1.2), RTS (7.8 +/- 0.5 vs. 7.7 +/- 0.6) and TRISS (0.98 +/- 0.1 vs.
      0.97 +/- 0.1). Men were significantly more frequent in group A (87.9% vs. 72.6%).
      When comparing injuries between groups, we observed that the motorcycle riders
      had significantly (p < 0.05) lower frequency of extradural hematomas (0.6% vs.
      2.1%), subdural hematomas (0.9% vs. 2.1%), subarachnoid hemorrhage (0.9% vs.
      2.2%), brain injury (1.2 vs. 3.6%), and severe head injuries (4.8% vs. 9.4% ), as
      well as higher frequency of diffuse axonal injury (1.6% vs. 0.7%), upper- (7.9%
      vs. 4.4%) and lower-limb fractures (7.7% vs. 5, 2%), and severe extremity lesions
      (20.6% vs. 12.6%). CONCLUSION: Compared to victims of other trauma mechanisms,
      motorcycle riders had a lower frequency and severity of head injuries, as well as
      increased frequency and severity of lesions in the extremities.

PMID- 22392321
TI  - [High prevalence of off-label and unlicensed drug prescribing in a Brazilian
      intensive care unit].
AB  - OBJECTIVE: To describe the use and determine the prevalence of off-label and
      unlicensed drug use prescribing in a pediatric intensive care unit in a
      Southeastern Brazilian hospital METHODS: Cross-sectional study of inpatients in a
      pediatric intensive care unit from May 2008 through January 2009. The
      classification according to the Brazilian regulatory agency (Agencia de
      Vigilancia Sanitaria - Anvisa) approval criteria was based on the Anvisa
      electronic package insert list, Pharmaceuticals Dictionary, and the analysis was
      conducted through R software. RESULTS: We analysed 1,054 prescription items for
      73 patients. Females predominated (52%), and the patients' age ranged from 0 to
      16 years. Among the prescribed items, 23.4% were off-label, 12.6% were
      unlicensed, 1.4% were both off-label and unlicensed, 86% had at least one item
      off-label, and 67% had at least one unlicensed drug. The most frequently
      prescribed therapeutic groups were systemic anti-bacterial, analgesic,
      psycholeptic, and antiasmathic agents. CONCLUSION: The current study results
      confirm the high prevalence of unlicensed and off-label drug use in a pediatric
      intensive care unit.

PMID- 22392322
TI  - [Evidence for the use of appetite suppressant drugs in Brazil: a
      pharmacoeconometric study].
AB  - OBJECTIVE: Analyze the use of appetite suppressants in Brazil in 2009, according
      to the characteristics of users, healthcare system, and other drugs. METHODS:
      Pharmaconeconometric study of cross-sectional data to analyze the relationship
      between the use of appetite suppressants (mg/per capita) and the independent
      variables selected (gender, race/color, age, schooling, income, health insurance
      coverage, and use of fluoxetine and chlordiazepoxide) using multiple linear
      regression analysis. This study used these variables in level of aggregation by
      states for 2009. The analyses were performed using the Gretl software. RESULTS:
      We highlight that Sao Paulo showed the highest use of appetite suppressants with
      97.3 mg/per capita, followed by Goias with 94.8 mg/per capita. The lowest use of
      appetite suppressants was seen in Ceara (3.8 mg/per capita). The biggest
      fluoxetine users were in Rio Grande do Sul, with 58.0 mg/per capita, and in
      Goias, with 51.5 mg/per capita. Ceara showed the lowest fluoxetine use (2.3
      mg/per capita). For chlordiazepoxide, the highest values were seen in Minas
      Gerais (7.5 mg/per capita) and in Rio de Janeiro (4.8 mg/per capita), while
      Amazonas (0.08 mg/per capita) showed the lowest use. Based on regression
      analysis, we can highlight: 1) the use of appetite suppressants is related to
      income, education, and fluoxetine use; and 2) race/color, gender, age, health
      insurance coverage, and use of chlordiazepoxide showed no relation to the use of
      appetite suppressants. CONCLUSION: These evidences may contribute to the
      improvement of regulatory actions, sanitary surveillance, and ethical conduct,
      particularly with regard to the concomitant use of appetite suppressants and
      fluoxetine, which is prohibited by the Federal Council of Medicine (Conselho
      Federal de Medicina) and also by Anvisa (Agencia Nacional de Vigilancia Sanitaria
      - National Health Surveillance Agency).

PMID- 22392323
TI  - [Analysis of similar drug labeling: potential medication errors].
AB  - OBJECTIVE: This study aimed to examine drug packaging and labeling, identifying
      similarities among them that may lead to medication errors, which may occur by
      unintentional substitution, in different sectors of the pharmacy of a university
      hospital in northeastern Brazil. METHODS: Cross-sectional observational study,
      which included 300 pharmaceutical presentations (150 pairs) that were
      photographed from May to December 2010. Concordance analysis of data related to
      the pictures of possibly similar packaging and labels was validated using the
      Kappa index. RESULTS: Of all drugs evaluated (n = 150), about 43% of "possibly
      similar drugs" were in the central pharmacy (n = 65) and were related to small
      volume parenteral solutions. The strength of interobserver agreement in the
      category "very similar to each other" was considered "satisfactory" (Kappa =
      0584) in 90.66% of the drugs evaluated (n = 136). The overall Kappa analysis of
      the study was 0.488. Variables with statistical significance were: "same color
      label or packaging", with the respective percentages for both primary and
      secondary packaging (52%-44%), p = 0.028; the variable "same color of drug
      presentation" obtained similar values and statistical significance to the
      previous variable; for the variable "same arrangement of words", the values found
      for both packages were close to 50%, p = 0.001; and for the variable "same color
      of the words", the percentages were: (50.7% - 44%) (p = 0.008). CONCLUSION: Our
      results indicate similarities related to the labeling of drugs with potential for
      errors, especially in dispensing, storage, and administration if preventive
      measures are not adopted.

PMID- 22392324
TI  - [Costs of the chain of treatment procedures in acute myocardial infarction in
      Brazilian reference and specialized hospitals].
AB  - OBJECTIVE: To present the methodology and the results of a field survey to assess
      the chain costs of procedures for treatment of acute myocardial infarction (AMI),
      carried out in 11 Brazilian reference and specialized hospitals. METHODS: The
      cost assessment used the cost per procedure and per pathology systems. The
      procedures associated with the treatment of AMI were organized and their logical
      sequence (protocols) was used to create a flowchart. Data collection tools
      gathered information on prices and quantities in 2008 (private, health insurance,
      SUS, and Brazilian Medical Association - AMB price lists), as well as the
      applicable costs. RESULTS: Overall, the total cost of the procedures involving
      the 'standard treatment' of AMI was R$ 12,873.69, if percutaneous coronary
      intervention (PCI) did not involve stent use. If the stent becomes necessary, the
      cost increases to R$ 23,461.87. CONCLUSION: Among the results, we emphasize the
      fact that the costs of the more expensive procedures did not present
      statistically significant variations between hospitals, regardless of their
      location, predominant clientele or legal nature, and the fact that hospitals that
      treat predominantly users of the Brazilian Unified Health System registered the
      lowest costs, albeit not statistically significant regarding the entire chain of
      procedures associated with the pathology.

PMID- 22392325
TI  - Combined spinal-epidural anesthesia and non-pharmacological methods of pain
      relief during normal childbirth and maternal satisfaction: a randomized clinical
      trial.
AB  - OBJECTIVE: The objective of this study was to compare maternal satisfaction with
      childbirth according to whether or not combined spinal-epidural anesthesia (CSE)
      of pain relief was used during labor. METHODS: A randomized, open clinical trial
      was performed with 70 pregnant women, 35 of whom received CSE anesthesia while 35
      received only non-pharmacological forms of pain relief during labor. The
      variables evaluated were visual analogue scale (VAS) pain score, maternal
      satisfaction with the technique of pain relief used during childbirth and with
      delivery, the patient's intention to request the same technique in a subsequent
      delivery, and loss of control during delivery. RESULTS: VAS pain score decreased
      significantly in patients receiving CSE during vaginal delivery. Furthermore,
      maternal satisfaction with the technique of pain relief and with delivery was
      higher in the CSE group, and around 97% of the patients would repeat the same
      technique at future deliveries compared to 82.4% of the women in the group using
      only non-pharmacological methods. With respect to the women's impressions of
      their control during delivery, approximately half the women in both groups felt
      that they had lost control at some point during the process. CONCLUSION: The use
      of CSE was associated with a significant reduction in VAS pain scores during
      delivery and with greater maternal satisfaction with the pain relief method and
      with the childbirth process.

PMID- 22392326
TI  - Double-blind randomized controlled trial of rolls fortified with
      microencapsulated iron.
AB  - OBJECTIVE: To evaluate the impact of the fortification of rolls with
      microencapsulated iron sulfate with sodium alginate on the hemoglobin levels in
      preschoolers as compared to controls. METHODS: Double-blind randomized controlled
      trial comprised of children aged 2 to 6 years with initial hemoglobin exceeding 9
      g/dL from four not-for-profit daycares randomly selected in the city of Sao Paulo
      - Brazil. Children of 2 daycares (n = 88) received rolls with fortified wheat
      flour as the exposed group (EC) and children of 2 daycares (n = 85) received
      rolls without fortification as the control group (CG) over a 24-week period.
      Rolls with 4 mg iron each were offered once a day, five days a week. Hemoglobin
      concentrations were determined in capillary blood by HemoCue(r) at three moments
      of trial: baseline (Ml), after 12 and 24 weeks of intervention (M2, M3). RESULTS:
      Hemoglobin concentration presented significant increase up to M3 in EG (11.7-12.5
      12.6 g/dL) and in CG (11.1-12.4-12.3 g/dL) with higher elevations in children
      initially with anemia. There was significant reduction in the occurrence of
      anemia from 22% to 9% in EG and from 47% to 8.2% in CG at M3. CONCLUSION: Rolls
      fortified with microencapsulated iron sulfate were well tolerated, increased
      hemoglobin levels and reduced the occurrence of anemia, but with no difference
      compared to the control group.

PMID- 22392327
TI  - Glucose disturbances in non-diabetic patients receiving acute treatment with
      methylprednisolone pulses.
AB  - OBJECTIVE: Methylprednisolone pulses are used in a variety of disease conditions,
      both for acute and chronic therapy. Although well tolerated, they increase
      glucose levels in both non-diabetic and diabetic patients. They may also be
      considered a significant risk for acute metabolic alterations. The purpose of
      this report is to determine the metabolic changes in blood glucose levels in non
      diabetic patients receiving methylprednisolone pulses and identify the presence
      of predictive factors for its development. METHODS: Observational, prospective
      study in 50 non-diabetic patients receiving 1 g intravenous methylprednisolone
      pulses for three consecutive days as an indication for diverse autoimmune
      disorders. Demographic, anthropometric, and metabolic variables were analyzed,
      and glucose, insulin and C-peptide levels after each steroid pulse were
      identified. Different variables and the magnitude of hyperglycemia were analyzed
      using Pearson's correlation. RESULTS: 50 patients were included, predominantly
      women (66%, n = 33). The average age was 41 +/- 14 years with a BMI of 26 +/- 3
      kg/m2. Baseline glucose was 83 +/- 10 mg/dL. After each steroid pulse, glucose
      increased to 140 +/- 28, 160 +/- 38 and 183 +/- 44, respectively (p < 0.001). C
      peptide and insulin concentrations increased significantly (p < 0.001). The
      prevalence of fasting hyperglycemia after each pulse was 68%, 94% and 98%,
      respectively. We found no correlation between the magnitude of hyperglycemia and
      the studied variables. CONCLUSION: Methylprednisolone pulses produced significant
      increases in fasting glucose in most patients without diabetes. Further studies
      are needed to define its role in long-term consequences.

PMID- 22392328
TI  - MicroRNAs as biomarkers for myocardial infarction.
AB  - MicroRNAs (miRs) are short non-coding RNA molecules involved in post
      transcriptional gene regulation by binding to the 3' untranslated region of a
      messenger RNA (mRNA), thereby inhibiting the translation or inducing mRNA
      destabilization. MiRs are generally considered to act as intracellular mediators
      essential for normal cardiac function, and their deregulated expression profiles
      have been associated with cardiovascular diseases. Recent studies have revealed
      the existence of freely circulating miRs in human peripheral blood, which are
      present in a stable nature. This has raised the possibility that miRs may be
      released in the circulation and can serve as novel diagnostic markers for acute
      or chronic human disorders, including myocardial infarction (MI). This review
      summarizes the recent findings of miRs that fulfill the criteria of candidate
      biomarkers for MI.

PMID- 22392330
TI  - Magnetic nanoparticles in magnetic resonance imaging and diagnostics.
AB  - Magnetic nanoparticles are useful as contrast agents for magnetic resonance
      imaging (MRI). Paramagnetic contrast agents have been used for a long time, but
      more recently superparamagnetic iron oxide nanoparticles (SPIOs) have been
      discovered to influence MRI contrast as well. In contrast to paramagnetic
      contrast agents, SPIOs can be functionalized and size-tailored in order to adapt
      to various kinds of soft tissues. Although both types of contrast agents have a
      inducible magnetization, their mechanisms of influence on spin-spin and spin
      lattice relaxation of protons are different. A special emphasis on the basic
      magnetism of nanoparticles and their structures as well as on the principle of
      nuclear magnetic resonance is made. Examples of different contrast-enhanced
      magnetic resonance images are given. The potential use of magnetic nanoparticles
      as diagnostic tracers is explored. Additionally, SPIOs can be used in diagnostic
      magnetic resonance, since the spin relaxation time of water protons differs,
      whether magnetic nanoparticles are bound to a target or not.

PMID- 22392331
TI  - Vaginal film drug delivery of the pyrimidinedione IQP-0528 for the prevention of
      HIV infection.
AB  - PURPOSE: Polymeric quick-dissolving films were developed as a solid dosage
      topical microbicide formulation for the vaginal delivery of the highly potent and
      non-toxic, dual-acting HIV nonnucleoside reverse transcriptase inhibitor (NNRTI)
      pyrimidinedione, IQP-0528. METHODS: Formulated from approved excipients, a
      polyvinyl alcohol (PVA) based film was manufactured via solvent casting methods.
      The film formulations were evaluated based upon quantitative physicochemical
      evaluations defined by a Target Product Profile (TPP) RESULTS: Films dosed with
      0.1% (w/w) of IQP-0528 disintegrated within 10 min with over 50% of drug released
      and near 100% total drug released after 30 min. The IQP-0528 films were found to
      be non-toxic in in vitro CEM-SS and PBMC cell-based assays and biologically
      active with sub-nanomolar efficacy against HIV-1 infection. In a 12 month
      stability protocol, the IQP-0528 films demonstrated no significant degradation at
      International Conference on Harmonization (ICH) recommended standard (25 degrees
      C/65% relative humidity (R.H.)) and accelerated (40 degrees C/75% R.H.)
      environmental conditions. CONCLUSIONS: Based on the above evaluations, a vaginal
      film formulation has been identified as a potential solid dosage form for the
      vaginal delivery of the topical microbicide candidate IQP-0528.

PMID- 22392334
TI  - (1)H, (15)N and (13)C assignments of the calcium bound S100P.
AB  - To determine the three-dimensional solution structure of the calcium bound S100P
      protein, the backbone and side chain resonance assignments of the S100P protein
      have been reported based on triple-resonance experiments using uniformly [(13)C,
      (15)N]-labeled calcium bound protein.

PMID- 22392332
TI  - Relationship between the affinity of PEO-PPO-PEO block copolymers for biological
      membranes and their cellular effects.
AB  - PURPOSE: The interactions of poly(ethylene oxide)-co-poly(propylene oxide) tri
      block copolymers (PEO-PPO-PEO block copolymers, Pluronics(r), Synperonics(r),
      Poloxamers) of differing chemical composition with cell membranes were
      systematically investigated in order to clarify the mechanisms behind their
      previously reported various cellular responses. METHODS: Relationships between
      the structural components of a defined series of PEO-PPO-PEO block copolymers and
      i) their interactions with biological membranes; ii) their cytotoxic potential
      were probed using a combination of haemolysis studies and cytotoxicity assays in
      the Caco-2 and HMEC-1 cell lines. RESULTS: The length of the PPO block as well as
      the PEO/PPO ratio were determinants of their membrane binding constant and
      cytotoxicity endpoints measured in the MTS and LDH assays. Similar 2D parabolic
      relationships were found between polymer composition and their affinity for
      membranes or their cytotoxicity potential. Cytotoxicity was related to the
      ability of the copolymers to form ion transversable pores within the cell
      membrane. CONCLUSIONS: The data suggest a link between the affinity of certain
      Pluronics for biological membranes and their cellular adverse effects. This first
      cell-based investigation of the interactions of Pluronics with biological
      membranes is an important step towards unravelling the complex mechanisms which
      govern the biological effects of widely used amphiphilic materials.

PMID- 22392335
TI  - (1)H, (13)C and (15)N resonance assignments of the Onconase FL-G zymogen.
AB  - Onconase((r)) FL-G zymogen is a 120 residue protein produced by circular
      permutation of the native Onconase((r)) sequence. In this construction, the wild
      type N- and C-termini are linked by a 16 residue segment and new N- and C-termini
      are generated at wild type positions R73 and S72. This novel segment linking the
      native N- and C-termini is designed to obstruct Onconase's((r)) active site and
      encloses a cleavage site for the HIV-1 protease. As a first step towards the
      resolution of its 3D structure and the study of its structure-function
      relationships, we report here the nearly complete NMR (1)H, (13)C and (15)N
      resonance chemical shift assignments at pH 5.2 and 35 degrees C (BMRB deposit no
      17973). The results presented here clearly show that the structure of the wild
      type Onconase((r)) is conserved in the FL-G zymogen.

PMID- 22392336
TI  - (1)H, (13)C, and (15)N backbone chemical shift assignments of StAR-related lipid
      transfer domain protein 5 (STARD5).
AB  - Steroidogenic acute regulatory (StAR)-related lipid transfer proteins possess a
      START (steroidogenic acute regulatory-related lipid transfer) domain. START
      domains are conserved protein modules involved in the non-vesicular intracellular
      transport of lipids and cholesterol in mammals. Fifteen mammalian proteins,
      divided in five subfamilies, are reported to possess a START domain. Members of
      the STARD4 subfamily, i.e. STARD4, 5 and 6 are essentially single START domains
      and are thought to be involved in the intracellular transport of cholesterol. No
      structure of a cholesterol-bound START domain from this family has been resolved
      yet. The determination of the structure of such a complex would contribute to a
      better understanding of the mechanism of ligand binding and transport by START
      domains, two unresolved aspects of their structural biology. In this context, we
      have undertaken the structure determination of a ligand-bound form of STARD5 by
      NMR. Here, we report the (1)H, (13)C and (15)N backbone resonance assignments of
      the ligand-free STARD5.

PMID- 22392337
TI  - (1)H, (13)C, and (15)N chemical shifts assignments for human endothelial monocyte
      activating polypeptide EMAP II.
AB  - Endothelial and monocyte-activating polypeptide II (EMAP II) is a cytokine that
      plays an important role in inflammation, apoptosis and angiogenesis processes in
      tumour tissues. Structurally, the EMAP II is a 169 amino acid residues long C
      terminal domain (residues 147-312) of auxiliary tRNA binding protein p43. In
      spite of existence in pdb databank of two X-ray structures there are some
      important aspects of EMAP II cytokine function which are still not fully
      understood in detail. To obtain information about 3D structure and backbone
      dynamic processes in solution we perform structure evaluation of human EMAP II
      cytokine by NMR spectroscopy. The standard approach to sequence-specific backbone
      assignment using 3D NMR data sets was not successful in our studies and was
      supplemented by recently developed 4D NMR experiments with random sampling of
      evolution time space. Here we report the backbone and side chain (1)H, (13)C, and
      (15)N chemical shifts in solution for recombinant EMAP II cytokine together with
      secondary structure provided by TALOS + software.

PMID- 22392338
TI  - Backbone resonance assignments of the C2 domain of coagulation factor VIII.
AB  - Factor VIII (FVIII, other clotting factors are named similarly) is a glycoprotein
      that circulates in the plasma bound to von Willebrand factor. During the blood
      coagulation cascade, activated FVIII (FVIIIa) binds to FIXa and activates FX in
      the presence of calcium ions and phospholipid membranes. The C1 and C2 domains
      mediate membrane binding that is essential for activation of the FVIIIa-FIXa
      complex. Here, (1)H, (13)C, and (15)N backbone chemical shift assignments are
      reported for the C2 domain of FVIII, including assignments for the residues in
      solvent-exposed loops. The NMR resonance assignments, along with further
      structural studies of membrane-bound FVIII, will advance understanding of blood
      clotting protein interactions.

PMID- 22392339
TI  - Resonance assignments of the 56 kDa chimeric avidin in the biotin-bound and free
      forms.
AB  - Avidin is a homotetrameric ~56 kDa protein found in chicken egg white. Avidin's
      ability to bind biotin with a very high affinity has widely been exploited in
      biotechnological applications. Protein engineering has further diversified
      avidin's feasibility. ChiAVD(I117Y) is a product of rational protein engineering.
      It is a hyperthermostable synthetic hybrid of avidin and avidin-related protein 4
      (AVR4). In this chimeric protein a 23-residue segment in avidin has been replaced
      with the corresponding sequence found in AVR4, and a point mutation at subunit
      interface 1-3 (and 2-4) has been introduced. Here we report the backbone and
      sidechain resonance assignments of the biotin-bound form of ChiAVD(I117Y) as well
      as the backbone resonance assignments of the free form.

PMID- 22392340
TI  - (1)H, (13)C, and (15)N chemical shift assignments for PfPMT, a
      phosphoethanolamine methyltransferase from Plasmodium falciparum.
AB  - Phosphoethanolamine methyltransferases (PMTs also known as PEAMTs) catalyze the
      three-step s-adenosyl-methionione-dependent methylation of phosphoethanolamine to
      form phosphocholine. These enzymes play an important function in the synthesis of
      phosphatidylcholine, the major phospholipid in the membranes of lower and higher
      eukaryotes, as well as in the production of the compatible solute and
      osmoprotectant glycine betaine in plants. Genetic studies in plants,
      Caenhorhabditis elegans and Plasmodium falciparum have demonstrated that
      disruption of PMT activity results in severe defects in important cellular
      processes such as development, replication, survival and sexual maturation and
      differentiation. Here we report chemical shift assignments for PfPMT, the PMT
      from Plasmodium falciparum. X-ray crystal structures have been recently reported
      for complexes of PfPMT, but the structure of the apoenzyme remains unknown. The
      solution structure of the apoenzyme will help to elucidate important details of
      the mechanism of substrate binding by PfPMT, as residues comprising the substrate
      binding site are inaccessible to solvent in the conformation evident in the
      available crystal structures. In addition to enabling determination of the
      solution structure of the apoenzyme, the assignments will facilitate additional
      investigations into the interaction of PfPMT with its substrates and inhibitors.

PMID- 22392341
TI  - Backbone (1)H, (13)C, and (15)N resonance assignments of guanylyl cyclase
      activating protein-1, GCAP1.
AB  - Guanylyl cyclase activating protein 1 (GCAP1), a member of the neuronal calcium
      sensor subclass of the calmodulin superfamily, confers Ca(2+)-dependent
      activation of retinal guanylyl cyclase that regulates the visual light response.
      GCAP1 is genetically linked to retinal degenerative diseases. We report backbone
      NMR chemical shift assignments of Ca(2+)-saturated GCAP1 (BMRB no. 18026).

PMID- 22392342
TI  - NMR assignment of a PDZ domain in complex with a HPV51 E6 derived N-terminally
      pyroglutamic acid modified peptide.
AB  - The resonance assignment of an amino-terminal pyroglutamic acid containing
      peptide derived from the E6 protein of human papillomavirus (HPV) type 51 in
      complex with PDZ domain 2 of hDlg/SAP-97 is reported. The assignments include
      (1)H, (13)C and (15)N resonances for the protein and peptide in the complex and
      all of the peptide's pyroglutamic acid nuclei.

PMID- 22392343
TI  - (1)H, (13)C and (15)N assignments of CdnL, an essential protein in Myxococcus
      xanthus.
AB  - CdnL, an essential protein in Myxococcus xanthus and several other bacteria, is a
      member of the large CarD_TRCF family of bacterial proteins that interact with RNA
      polymerase. Structural analyses of the 164-residue M. xanthus CdnL by NMR is
      complicated because of broadening, and hence overlap, of the signals due to the
      self-association and the monomer-dimer equilibrium that occurs in solution. Here,
      we report (1)H, (13)C and (15)N assignments for CdnL achieved by analyzing its
      NMR spectra on the basis of the complete assignment obtained in this study for
      the 68-residue N-terminal fragment of CdnL (CdnLNt) together with those we
      described previously for the stable, protease-resistant, 110-residue C-terminal
      domain (CdnLCt). This approach relied on our observation that many of the CdnLNt
      and CdnLCt chemical shifts matched closely with those of the equivalent residues
      in the full-length protein. Our assignments provide the crucial first step in the
      structural analysis of CdnL and this functionally important family of bacterial
      proteins.

PMID- 22392344
TI  - Backbone and sidechain (1)H, (15)N and (13)C assignments of Tyrosine Phosphatase
      related to Biofilm formation A (TpbA) of Pseudomonas aeruginosa.
AB  - The backbone and side chain resonance assignments of the Tyrosine Phosphatase
      related to Biofilm formation A (TpbA) of Pseudomonas aeruginosa have been
      determined based on triple-resonance experiments using uniformly [(13)C,(15)N]
      labeled protein. This assignment is the first step towards the determination of
      the 3-dimensional structure of TpbA.

PMID- 22392345
TI  - Strong pi-delocalization and substitution effect on electronic properties of
      dithienylpyrrole-containing bipyridine ligands and corresponding ruthenium
      complexes.
AB  - The first dithienylpyrrole (DTP)-based bipyridine ligands has been prepared and
      coordinated with ruthenium to give the corresponding homoleptic complexes.
      Bipyridine was bound at pyrrole (DTP(1)) or thiophene (DTP(2)) ring. A strong
      bathochromic effect was obtained by switching from pyrrole to thiophene for
      ligands and complexes. Interestingly the DTP(2) series offered a wide absorption
      window from UV to visible domain with an almost constant absorbance. These
      effects are due to a larger extent of delocalization as supported by DFT
      calculations and photophysical measurements.

PMID- 22392346
TI  - Association of mammographic density with hormone receptors in invasive breast
      cancers: results from a case-only study.
AB  - For many breast cancer (BC) risk factors, there is growing evidence concerning
      molecular subtypes for which the risk factor is specific. With regard to
      mammographic density (MD), there are inconsistent data concerning its association
      with estrogen receptor (ER) and progesterone receptor (PR) expression. The aim of
      our study was to analyze the association between ER and PR expression and MD. In
      our case-only study, data on BC risk factors, hormone receptor expression and MD
      were available for 2,410 patients with incident BC. MD was assessed as percent MD
      (PMD) using a semiautomated method by two readers for every patient. The
      association of ER/PR and PMD was studied with multifactorial analyses of
      covariance with PMD as the target variable and including well-known factors that
      are also associated with MD, such as age, parity, use of hormone replacement
      therapy, and body mass index (BMI). In addition to the commonly known
      associations between PMD and age, parity, BMI and hormone replacement therapy, a
      significant inverse association was found between PMD and ER expression levels.
      Patients with ER-negative tumors had an average PMD of 38%, whereas patients with
      high ER expression had a PMD of 35%. A statistical trend toward a positive
      association between PMD and PR expression was also seen. PMD appears to be
      inversely associated with ER expression and may correlate positively with PR
      expression. These effects were independent of other risk factors such as age,
      BMI, parity, and hormone replacement therapy, possibly suggesting other pathways
      that mediate this effect.

PMID- 22392347
TI  - Toxicity of amphetamines: an update.
AB  - Amphetamines represent a class of psychotropic compounds, widely abused for their
      stimulant, euphoric, anorectic, and, in some cases, emphathogenic, entactogenic,
      and hallucinogenic properties. These compounds derive from the beta
      phenylethylamine core structure and are kinetically and dynamically characterized
      by easily crossing the blood-brain barrier, to resist brain biotransformation and
      to release monoamine neurotransmitters from nerve endings. Although amphetamines
      are widely acknowledged as synthetic drugs, of which amphetamine,
      methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are well
      known examples, humans have used natural amphetamines for several millenniums,
      through the consumption of amphetamines produced in plants, namely cathinone
      (khat), obtained from the plant Catha edulis and ephedrine, obtained from various
      plants in the genus Ephedra. More recently, a wave of new amphetamines has
      emerged in the market, mainly constituted of cathinone derivatives, including
      mephedrone, methylone, methedrone, and buthylone, among others. Although
      intoxications by amphetamines continue to be common causes of emergency
      department and hospital admissions, it is frequent to find the sophism that
      amphetamine derivatives, namely those appearing more recently, are relatively
      safe. However, human intoxications by these drugs are increasingly being
      reported, with similar patterns compared to those previously seen with classical
      amphetamines. That is not surprising, considering the similar structures and
      mechanisms of action among the different amphetamines, conferring similar
      toxicokinetic and toxicological profiles to these compounds. The aim of the
      present review is to give an insight into the pharmacokinetics, general
      mechanisms of biological and toxicological actions, and the main target organs
      for the toxicity of amphetamines. Although there is still scarce knowledge from
      novel amphetamines to draw mechanistic insights, the long-studied classical
      amphetamines-amphetamine itself, as well as methamphetamine and MDMA, provide
      plenty of data that may be useful to predict toxicological outcome to improvident
      abusers and are for that reason the main focus of this review.

PMID- 22392348
TI  - Building a consumer base for trauma-focused cognitive behavioral therapy in a
      state system of care.
AB  - This paper documents the scope and limitations of an outreach effort to build a
      consumer base for Trauma-focused cognitive behavioral therapy in a state public
      mental health system for children. Three key aspects are discussed: the fostering
      of an informed referral network, the development of screening and identification
      services, and the engagement of families. Referral, screening and engagement are
      each examined against the backdrop of existing literature on implementation and
      dissemination. Each aspect of the implementation plan is described in detail-as
      are the barriers encountered and lessons learned during the course of execution.
      We provide several recommendations to assist other efforts to implement Evidence
      Based Treatments into state systems of care.

PMID- 22392349
TI  - Relationship between CDT and disease activity in rheumatoid arthritis.
AB  - The aim of this study was to estimate the serum concentration of carbohydrate
      deficient transferrin (CDT) in patients with rheumatoid arthritis (RA) and the
      relationship between the CDT level and disease activity in RA patients. Studies
      were carried out in 47 female patients with RA and 32 healthy women. Disease
      activity of RA was evaluated using the 28-joint count Disease Activity Score (DAS
      28). Serum CDT was determined by particle-enhanced immunononephelometry using the
      N Latex CDT test. Patients with RA had significantly lower serum concentrations
      of CDT compared with controls. The correlation study showed the significant
      negative relationship between CDT and DAS 28 (r = - 0.483, p = 0.011). There were
      no correlations between serum CDT level and patient's age, disease duration,
      number of tender and swollen joints, and degree of disability evaluated by the
      Health Assessment Questionnaire. The level of CDT in patients with RA was
      significantly decreased and confirms the changes in transferrin glycosylation
      which are dependent on the disease activity. Therefore, measurement of CDT in the
      sera of patients with RA can be useful for the evaluation of disease activity in
      these patients.

PMID- 22392350
TI  - Effect of ascorbic acid on reactive oxygen species production in chemotherapy and
      hyperthermia in prostate cancer cells.
AB  - Cellular reactive oxygen species (ROS) production is increased by both
      temperature and anticancer drugs. Antioxidants are known to suppress ROS
      production while cancer patients may take them as dietary supplement during
      chemotherapy and hyperthermic therapy. We examined changes in ROS production in
      prostate cancer cells in the presence of various anticancer drugs and
      antioxidants at different temperatures. ROS production was increased with
      temperature in cancer cells, but not in normal cells; this increase was potently
      inhibited by ascorbic acid. ROS production was also increased in the presence of
      some anticancer drugs, such as vinblastine, but not by others. Dietary
      antioxidant supplements, such as beta-carotene, showed variable effects. Ascorbic
      acid potently inhibited ROS production, even in the presence of anticancer drugs,
      while beta-carotene showed no inhibition. Accordingly, our results suggest that
      cancer patients should carefully choose antioxidants during their cancer
      chemotherapy and/or hyperthermic therapy.

PMID- 22392351
TI  - Substrate-mediated enhanced activity of Ru nanoparticles in catalytic
      hydrogenation of benzene.
AB  - The impact of carbon substrate-Ru nanoparticle interactions on benzene and
      hydrogen adsorption that is directly related to the performance in catalytic
      hydrogenation of benzene has been investigated by first-principles based
      calculations. The stability of Ru(13) nanoparticles is enhanced by the defective
      graphene substrate due to the hybridization between the dsp states of the Ru(13)
      particle with the sp(2) dangling bonds at the defect sites. The local curvature
      formed at the interface will also raise the Ru atomic diffusion barrier, and
      prohibit the particle sintering. The strong interfacial interaction results in
      the shift of averaged d-band center of the deposited Ru nanoparticle, from -1.41
      eV for a freestanding Ru(13) particle, to -1.17 eV for the Ru/Graphene
      composites, and to -1.54 eV on mesocellular foam carbon. Accordingly, the
      adsorption energies of benzene are increased from -2.53 eV for the
      Ru/mesocellular foam carbon composites, to -2.62 eV on freestanding Ru(13)
      particles, to -2.74 eV on Ru/graphene composites. A similar change in hydrogen
      adsorption is also observed, and all these can be correlated to the shift of the
      d-band center of the nanoparticle. Thus, Ru nanoparticles graphene composites are
      expected to exhibit both high stability and superior catalytic performance in
      hydrogenation of arenes.

PMID- 22392352
TI  - Breast cancer local therapy: what is its effect on mortality?
AB  - Until recently, the concept of biological predeterminism appeared pre-eminent and
      a worthy successor to the Halstedian doctrine of centrifugal spread of cancer.
      However, evidence has now emerged from clinical trials to cast doubt on the
      universal application of this concept to breast tumors. Prevention of local
      recurrence can save lives, local control does matter, and rates of local
      recurrence should be minimized in the first 5 years. In up to one quarter of
      cases of local recurrence the locally recurring disease will be a determinant and
      not simply a marker of risk for distant relapse and death. Both types of local
      recurrence are manifestations of the same biological processes and reflect
      intrinsic behavior of the tumor. This principle applies to reduction in local
      relapse from both adjuvant radiotherapy and surgical modalities.

PMID- 22392353
TI  - Prolactin promotes hepatocellular carcinoma through Janus kinase 2.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one human cancer with obvious
      gender disparity. This study investigated the association of aberrant prolactin
      levels with HCC risk and the potential impacts on HCC of the prolactin receptor
      (PRLR)/Janus kinase 2 (JAK2) signaling. METHODS: Serum prolactin of 63 HCC
      patients and 162 subjects without HCC was measured by radioimmunoassay. The
      expressions of PRLR and phosphorylated JAK2 (p-JAK2) in 82 retrospectively
      collected HCC specimens were evaluated by immunohistochemistry and further
      incorporated into the survival analysis. The immunoblotting and proliferation
      assays were used to analyze the effects of PRLR/JAK2 signaling on liver cancer
      cells with prolactin treatment. RESULTS: Serum prolactin level was significantly
      higher in HCC patients than in controls. Hepatocellular carcinoma patients with
      high p-JAK2 expression had a significantly higher postoperative risk than those
      with low p-JAK2 expression. Moreover, results from the multivariate analysis
      indicated the prognostic role of p-JAK2 expression with respect to overall
      survival in HCC patients. In addition, the Kaplan-Meier survival curve showed
      that high p-JAK2 expression was associated with poor survival in HCC patients
      with high PRLR expression. The immunoblotting assay showed that prolactin induced
      the expression of both p-JAK2 and cyclin D1 in Hep-G2 cells. Importantly, the
      proliferative effects induced by prolactin could be effectively attenuated by
      adding AG490, a JAK2 inhibitor. CONCLUSIONS: Increased circulating prolactin was
      found in HCC patients and high p-JAK2 expression could predict poor overall
      survival in those patients expressing high PRLR. In addition, prolactin
      contributed to the proliferation of liver cancer cells through PRLR/JAK2
      signaling.

PMID- 22392354
TI  - Desarda versus Lichtenstein technique for primary inguinal hernia treatment: 3
      year results of a randomized clinical trial.
AB  - BACKGROUND: The Shouldice method and other tissue-based techniques are still
      acknowledged to be acceptable for primary inguinal hernia repair according to the
      European Hernia Society guidelines. Desarda's technique, presented in 2001, is an
      original hernia repair method using an undetached strip of external oblique
      aponeurosis. This randomized trial compared outcomes after hernia repair with
      Desarda (D) and mesh-based Lichtenstein (L) techniques. METHODS: A total of 208
      male patients were randomly assigned to the D or L group (105 vs. 103,
      respectively). The primary outcomes measured were recurrence and chronic pain.
      Additionally, early and late complications, foreign body sensation, and return to
      everyday activity were examined in hospital and at 7, 30 days, and 6, 12, 24, and
      36 months after surgery. RESULTS: During the follow-up, two recurrences were
      observed in each group (p = 1.000). Chronic pain was experienced by 4.8 and 2.9%
      of patients from groups D and L, respectively (p = 0.464). Foreign body sensation
      and return to activity were not different between the groups. There was
      significantly less seroma production in the D group (p = 0.004). CONCLUSIONS: The
      results of primary inguinal hernia repair with the Desarda and Lichtenstein
      techniques are comparable at the 3-year follow-up. The technique may potentially
      increase the number of tissue-based methods available for treating groin hernias.

PMID- 22392355
TI  - Snapshot of surgical activity in rural Ethiopia: is enough being done?
AB  - BACKGROUND: Surgical conditions are responsible for a significant burden of the
      disease prevalence in sub-Saharan Africa. However, there is a paucity of data
      surrounding the amount and availability of surgical care. Few surveys exist that
      document current rates of surgical activity in the low-income setting, and most
      figures rely on the country estimates. We aim to document accurately the rates of
      surgery at the district level. METHODS: We performed a retrospective survey of
      surgical activity in 10 hospitals in the Southern Nation and Nationalities
      Peoples' Region of Ethiopia using a standardized data collection form. We also
      performed structured interviews with hospital directors. RESULTS: Surgical output
      varied across the hospitals from 56 to 421 operations per year per 100,000
      catchment population. The most commonly performed operation was cesarean section
      (29% of major procedures). Emergency surgery accounted for 55% of operations,
      with the most frequent emergency operation being cesarean section. The overall
      cesarean section rate was alarmingly low at 0.6%. There are only 76 health
      workers that are providing a surgical service to this sample population of 12.9
      million people. CONCLUSIONS: The rates of surgery found here were very low,
      consistent with the huge shortage of health workers providing a surgical service.
      The low cesarean section rate indicates that there is a large unmet surgical
      disease burden at the population level, and more comprehensive surveys are
      required to investigate this further. The most important steps to tackle the
      problem of deficiencies in global surgery are to increase access to surgical care
      and the surgical workforce capacity.

PMID- 22392357
TI  - Evaluation of the appendicitis inflammatory response score for patients with
      acute appendicitis.

PMID- 22392356
TI  - Robot-assisted thoracoscopic lymphadenectomy along the left recurrent laryngeal
      nerve for esophageal squamous cell carcinoma in the prone position: technical
      report and short-term outcomes.
AB  - BACKGROUND: Meticulous mediastinal lymphadenectomy frequently induces recurrent
      laryngeal nerve palsy (RLNP). Surgical robots with impressive dexterity and
      precise dissection skills have been developed to help surgeons perform
      operations. The objective of this study was to determine the impact on short-term
      outcomes of robot-assisted thoracoscopic radical esophagectomy performed on
      patients in the prone position for the treatment of esophageal squamous cell
      carcinoma, including its impact on RLNP. METHODS: A single-institution
      nonrandomized prospective study was performed. The patients (n = 36) with
      resectable esophageal squamous cell carcinoma were divided into two groups:
      patients who agreed to robot-assisted thoracoscopic esophagectomy with total
      mediastinal lymphadenectomy performed in the prone position (n = 16, robot
      assisted group) without insurance reimbursement, and those who agreed to undergo
      the same operation without robot assistance but with health insurance coverage (n
      = 20, control group). These patients were observed for 30 days following surgery
      to assess short-term surgical outcomes, including the incidence of vocal cord
      palsy, hoarseness, and aspiration. RESULTS: Robot assistance significantly
      reduced the incidence of vocal cord palsy (p = 0.018) and hoarseness (p = 0.015)
      and the time on the ventilator (p = 0.025). There was no in-hospital mortality in
      either group. There were no significant differences between the two groups with
      respect to patient background, except for the use of preoperative therapy (robot
      assisted group <control, p = 0.003). There were no significant differences in
      estimated blood loss, operating time, number of dissected lymph nodes,
      completeness of resection, or the incidence of the other complications, except
      for anastomotic leakage (p = 0.038). CONCLUSION: Robot-assisted thoracoscopic
      esophagectomy with total mediastinal lymphadenectomy is feasible and safe. This
      method shows promise in preventing RLNP.

PMID- 22392359
TI  - Inorganic salts in purely ionic liquid media: the development of High Ionicity
      Ionic Liquids (HIILs).
AB  - This work explores the possibility of increasing the ionicity of ionic liquids
      via the solubilization of inorganic salts in their midst. The resulting purely
      ionic media-distinct ionic liquid plus inorganic salt mixtures-are liquid in an
      extensive concentration range and can be aptly denominated High Ionicity Ionic
      Liquids (HIILs).

PMID- 22392358
TI  - Single-incision transperitoneal laparoscopic left adrenalectomy.
AB  - BACKGROUND: Laparoscopic adrenalectomy via three or four trocars is a well
      established procedure. This report describes the initial experience with single
      incision laparoscopic surgery (SILS) using the transperitoneal approach for left
      adrenalectomy. METHODS: Between April 2010 and August 2011, all consecutive
      patients with adrenal masses, including Conn's syndrome, Cushing's adenoma, and
      nonfunctional adrenal tumors, who agreed to undergo SILS adrenalectomy were
      included in a prospective study. The left 2.5-cm subcostal incision was the sole
      point of entry. Data of patients who underwent SILS adrenalectomy were compared
      with those from an uncontrolled group of patients who underwent conventional
      laparoscopic adrenalectomy during the same study period. RESULTS: There were 20
      patients in each study group (20 men, 20 women; mean age [SD] = 50 [6.5] years).
      SILS was successfully performed and none of the patients required conversion to
      an open procedure. In one case of SILS procedure, an additional lateral 5-mm port
      was needed for retraction of the kidney. The mean (SD) duration of the operation
      was 95 (20) min in the SILS group and 80 (8) min in the conventional laparoscopic
      adrenalectomy group (p = 0.052). There were no intraoperative or postoperative
      complications. There were no differences between the two study groups with
      respect to postoperative pain, number of patients who resumed oral intake within
      the first 24 h, final pathologic diagnosis, and length of hospital stay.
      CONCLUSION: SILS left adrenalectomy is a technically feasible and safe procedure
      in carefully selected patients. The definitive clinical, aesthetic and functional
      advantages of this technique require further analysis.

PMID- 22392360
TI  - What can we know from pituitary-adrenal hormones about the nature and
      consequences of exposure to emotional stressors?
AB  - Exposure to stress induces profound physiological and behavioral changes in the
      organisms and some of these changes may be important regarding stress-induced
      pathologies and animal models of psychiatric diseases. Consequences of stress are
      dependent on the duration of exposure to stressors (acute, chronic), but also of
      certain characteristics such as intensity, controllability, and predictability.
      If some biological variables were able to reflect these characteristics, they
      could be used to predict negative consequences of stress. Among the myriad of
      physiological changes caused by stress, only a restricted number of variables
      appears to reflect the intensity of the situation, mainly plasma levels of ACTH
      and adrenaline. Peripheral hypothalamic-pituitary-adrenal (HPA) hormones (ACTH
      and corticosterone) are also able to reflect fear conditioning. In contrast, the
      activation of the HPA axis is not consistently related to anxiety as evaluated by
      classical tests such as the elevated plus-maze. Similarly, there is no consistent
      evidence about the sensitivity of the HPA axis to psychological variables such as
      controllability and predictability, despite the fact that: (a) lack of control
      over aversive stimuli can induce behavioral alterations not seen in animals which
      exert control, and (b) animals showed clear preference for predictable versus
      unpredictable stressful situations. New studies are needed to re-evaluate the
      relationship between the HPA axis and psychological stress characteristics using
      ACTH instead of corticosterone and taking advantages of our current knowledge
      about the regulation of this important stress system.

PMID- 22392361
TI  - Adjuvant therapy in stage I carcinoma of the breast: the influence of multigene
      analyses and molecular phenotyping.
AB  - BACKGROUND: Breast Health International and the Kimmel Cancer Center of Thomas
      Jefferson University cosponsored a consensus conference that included an
      international group of experts. METHODS: Since the adoption of adjuvant
      chemotherapy for stage I, lymph node-negative breast cancers in 1988,
      investigators have tried to "fine-tune" the treatment criteria. At this consensus
      conference, the group debated recommendations for adjuvant hormone and cytotoxic
      chemotherapy in stage I breast cancers. RESULTS: Discussions during the
      conference addressed issues of adjuvant therapy for stage I breast cancer and the
      influence of multigene analyses and molecular phenotyping. The panelists
      discussed various demographic, morphologic, biologic, and genetic factors
      expressed by individual tumors and their influence on treatment decisions.
      CONCLUSIONS: The panel tried to create guidelines for the consideration of
      adjuvant treatment of these patients, including both hormone and cytotoxic
      regimens. They also encouraged further research into the molecular analysis of
      breast cancers and the introduction of clinical trials based on current data,
      although they concluded that it is too early to add any of those analyses into
      the decision-making algorithms of recommendations for the treatment of stage I
      breast cancer.

PMID- 22392364
TI  - Nutrition Issues in Codex: Health Claims, Nutrient Reference Values and WTO
      Agreements-A Conference Report : 11 November 2011, Kronberg, Germany.

PMID- 22392363
TI  - Chemical reactivity in the framework of pair density functional theories.
AB  - Chemical reactivity descriptors are derived within the framework of the pair
      density functional theory. These indices provide valuable information about
      bonding rearrangements and activating mechanisms upon electrophilic or
      nucleophilic reactions. Indices derived and tested in this work represent
      nonlocal counterparts of the local reactivity indices derived in the context of
      conceptual density functional theory (CDFT) and frequently used in reactivity
      studies; the Fukui function, the local softness and the dual descriptor. In this
      work, we show how these nonlocal indices provide a quantum chemical basis to
      explain the success of qualitative resonance models in chemical reactivity
      predictions. Also, local information is implicitly contained as CDFT indices are
      obtained by simple integration. As illustrative examples, we have considered in
      this work the Markovnikov's rule, the reactivity of enolate anion, the
      nucleophilic conjugate addition to alpha,beta-unsaturated compounds and the
      electrophilic aromatic substitution of benzene derivatives. The densities used in
      this work were obtained with Hartree-Fock, Kohn-Sham DFT, and singles and doubles
      configuration interaction (CISD) approaches.

PMID- 22392362
TI  - Targeting neuro-inflammatory cytokines and oxidative stress by minocycline
      attenuates quinolinic-acid-induced Huntington's disease-like symptoms in rats.
AB  - Recent experimental and clinical reports support the fact that the minocycline
      exhibits significant neuroprotective activity in neurodegenerative diseases.
      However, its mechanism of neuroprotection is still far from our understanding.
      Besides, minocycline does not always produce neuroprotective effect. Therefore,
      this study has been designed to explore the possible mechanism of minocycline in
      experimental model of HD in rats. Intrastriatal administration of quinolinic acid
      caused a significant reduction in body weight, motor dysfunction (impaired
      locomotor activity, rotarod performance, and beam walk test), oxidative damage
      (as evidenced by increase in lipid peroxidation, nitrite concentration, and
      depletion of super oxide dismutase and catalase), increased TNF-alpha and IL-6
      levels as compared to the sham-treated animals. Minocycline (25, 50, and 100
      mg/kg) treatment (for 21 days) significantly improved body weight, locomotor
      activity, rotarod performance, balance beam walk performance, oxidative defense,
      attenuated TNF-alpha and IL-6 levels as compared to quinolinic-acid (QA)-treated
      animals. This study provides evidence that minocycline might have neuroprotective
      effect against QA-induced Huntington-like behavioral, biochemical alterations,
      and neuroinflammation in rats.

PMID- 22392366
TI  - Negotiating identity transition when leaving forensic hospitals.
AB  - The transition from hospital patient to community resident is something which is
      far from straightforward. For those with multiple labels of disability,
      chronicity and criminal offending behaviours this transition is particularly
      complicated. This article reports on a study of accounts provided by a hard-to
      reach group of patients and their workers in one region of the UK. Through the
      use of 59 in-depth interviews with conditionally discharged persons, community
      mental health nurses and social workers, everyday understandings of the process
      of discharge and reintegration were investigated. The primary focus was on how
      identity was handled in the talk of discharged persons and what workers said
      about this. Analysis focused upon the action-oriented nature of accounts related
      to discharge, community return and attempts to construct viable identities in the
      outside world. This study found that stories did the work of loosening previous
      labels. Illness as mitigation was deployed as an important resource for this
      purpose. Deviant labels signifying mental illness and criminality presented
      enduring identity-threats. It was found that as they adjust to return to the
      community, individuals deploy particular types of identity talk to neutralize
      ascriptions of continuing deviance and make claims to normality. Workers for
      their part supported illness as mitigation but continued to orient towards risk
      as an enduring identity label. In their day-to-day lives the accomplishment of
      'ordinary' identities was a continuing task of discharged persons in maintaining
      community return.

PMID- 22392367
TI  - Neoliberalism, welfare policy and health: a qualitative meta-synthesis of single
      parents' experience of the transition from welfare to work.
AB  - Following the United States' lead, the emergence of neoliberal welfare policy
      across the western world has resulted in employment programmes for single
      parents, who are predominantly single mothers. While some governments claim that
      employment will improve single parents' incomes and well-being, researchers
      dispute that single parents can unproblematically move into the workforce, with
      net positive effects. While researchers have quantified the socio-economic effect
      of these programmes, in particular on participant health, no study has yet
      synthesized participants' experiences of welfare-to-work. Here, I present a meta
      synthesis of eight qualitative health-related studies of single parents' (and
      exclusively single mothers') welfare-to-work transition. I report that single
      mothers faced a combination of health and economic issues which made their
      transition from welfare to work difficult, including degrees of poor physical and
      mental health. For participants in the United States, these health issues were
      often compounded by a loss of health benefits on moving into low-wage employment.
      In countries where a return to employment was required before children reached
      school age, a lack of affordable and appropriate child care, especially for
      children with health problems, exacerbated these difficulties. As a result of
      scarce resources, single mothers in receipt of welfare benefits often relied on
      food banks or went without food. A return to the workforce did not alleviate this
      problem as additional child care and reduced government subsidies depleted the
      funds available for food. I conclude that welfare-to-work policies are
      underpinned by the neoliberal assumption that the market more efficiently
      distributes resources than the State. However, for the women in the studies
      examined here, labour market participation often depleted access to essential
      resources. Interventions to address the 'problem' of welfare dependency must
      recognize the complex interplay between work incentives and disincentives and the
      care-work of single mothers.

PMID- 22392368
TI  - Capillary electrophoresis for simultaneous analysis of heparin, chondroitin
      sulfate and hyaluronic acid and its application in preparations and synovial
      fluid.
AB  - A simple and accurate capillary electrophoresis (CE) method was developed to
      simultaneously separate and quantify heparin, chondroitin sulfate and hyaluronic
      acid. The relative standard deviations (intra-day) of migration time, peak height
      and peak area for heparin, chondroitin sulfate and hyaluronic acid were lower
      than 1.11, 5.45 and 2.82%, respectively. The limits of detection of heparin,
      chondroitin sulfate and hyaluronic acid were 0.91, 0.12 and 9.04 * 10(-3) mg/mL,
      respectively. The developed electrophoretic method was successfully applied to
      the analysis of commercial drug products and biological samples containing
      chondroitin sulfate and/or hyaluronic acid. The recoveries for chondroitin
      sulfate and hyaluronic acid were in the range of 95.9 ~107.0%. This was the first
      time the content of hyaluronic acid in the synovial fluids from osteoarthritic
      rabbits was investigated by CE. The results suggested that hyaluronic acid in the
      synovial fluids from osteoarthritic rabbits may be further metabolized and the
      administration of chondroitin sulfate or hyaluronic acid could affect the content
      and metabolism of hyaluronic acid in the synovial fluids. The developed CE method
      was simple to implement without sample pretreatment such as depolymerisation,
      very repeatable and easily transferred from lab to lab.

PMID- 22392369
TI  - Gas chromatographic determination of guanidino compounds in uremic patients using
      glyoxal as derivatizing reagent.
AB  - The guanidino compounds guanidine, methylguanidine, guanidinoacetic acid,
      guanidinopropionic acid, guanidinobutyric acid and guanidinosuccinic acid were
      eluted and separated after pre-column derivatization with glyoxal from an HP-5
      column (30 m * 0.32 mm i.d.) with film thickness 0.25 um at an initial column
      temperature of 100  degrees C for 2 min, with ramping of 20 degrees C/min up to
      250  degrees C and a nitrogen flow rate of 3 mL/min. Detection was by flame
      ionization detection. Linear calibrations were observed within 0.1-20.0 umol/L,
      with limit of detection within 0.024-0.034 umol/L for each compound. The
      separation was repeatable with relative standard deviation (RSD) (n = 6) within
      1.2-1.8 and 1.1-1.6% in terms of retention time and peak height/peak area,
      respectively. The method was applied for the determination of the guanidino
      compounds from serum of uremic patients (n = 7) and healthy volunteers (n = 8),
      and amounts were observed within 1.33-11.71 and 0.07-0.39 umol/L with RSD 1.1-3.5
      and 1.1-3.0%, respectively. The results were further supported by the standard
      addition method.

PMID- 22392370
TI  - The role of renal denervation in the treatment of heart failure.
AB  - The heart and kidney interact in terms of hemodynamics and neurohumoral
      regulatory mechanisms, and this helps to maintain circulatory homeostasis under
      normal conditions. However, the normal regulatory mechanisms become inappropriate
      in the setting of congestive heart failure (CHF), and significant renal
      dysfunction often develops in CHF patients. Activation of renal sympathetic
      efferent nerves causes renin release, sodium and water retention, and reduced
      renal blood flow, all hallmarks of the renal manifestations of CHF. An increase
      in plasma levels of angiotensin II that is mediated in part by renal sympathetic
      activation has an effect on the central nervous system to further increase global
      sympathetic tone. Renal sympathetic activity can be assessed clinically by renal
      norepinephrine spillover, and an increase in renal norepinephrine spillover in
      CHF predicts reduced survival. In addition to efferent sympathetic activation,
      activation of renal sensory nerves in CHF may cause a reflex increase in
      sympathetic tone that contributes to elevated peripheral vascular resistance and
      vascular remodeling as well as left ventricular remodeling and dysfunction. In
      animal models of heart failure, surgical renal denervation has been shown to
      improve both renal and ventricular function. Although surgical renal denervation
      has long been known to lower blood pressure and improve survival in patients with
      hypertension, the invasive nature of this approach and its associated
      complications has limited its appeal. However, a novel catheter-based device has
      recently been introduced that specifically interrupts both efferent and afferent
      renal nerves, and there is significant interest in the use of this device to
      treat both hypertension and CHF. Several ongoing clinical trials are
      investigating the safety and efficacy of renal denervation in patients with CHF.

PMID- 22392371
TI  - Multiplex flow-through immunoassay formats for screening of mycotoxins in a
      variety of food matrices.
AB  - Two multi-analyte flow-through immunoassay formats for rapid detection of
      mycotoxins in a variety of food matrices (peanut cake, maize, and cassava flour)
      were developed and evaluated. The selected food matrices are typical staple foods
      and export products for most low-income communities around the world. The assay
      formats included gel-based and membrane-based flow-through assays and were based
      on the principle of indirect enzyme-linked immunosorbent assay. Using the same
      immunoreagents, the performance characteristics of both assays were compared. To
      the best of our knowledge, this is the first report on such a comparison. The gel
      based format was developed to screen for ochratoxin A, fumonisin B(1),
      deoxynivalenol, and zearalenone detection at cut-off values of 3, 1,250, 1,000,
      and 200 MUg kg(-1), respectively, while the membrane-based format can be used to
      screen ochratoxin A, aflatoxin B(1,) deoxynivalenol, and zearalenone at the
      following cut-offs: 3, 5, 700, and 175 MUg kg(-1), respectively. The
      applicability of these assay formats was demonstrated by evaluating the
      performance characteristics of both tests through performing multiple experiments
      on different days. Both assays were further evaluated by analyzing naturally
      contaminated samples in the laboratory and also in the field under tropical
      conditions (Cameroon, West Africa). The false-negative rate with both formats was
      less than 5%, which is in good agreement with Commission Decision 2002/657/EC
      regarding the performance of analytical methods intended for screening purposes.

PMID- 22392372
TI  - Binding interface of cardiac potassium channel proteins identified by hydrogen
      deuterium exchange of synthetic peptides.
AB  - Three synthetic peptides, derived from the human potassium channel proteins Ether
      a-go-go-related gene (HERG), KCNQ1, and KCNE1, were investigated by hydrogen
      deuterium exchange coupled with electron-transfer dissociation mass spectrometry
      at single residue resolution. Each amino acid residue in the first half of the
      HERG peptide incorporated deuterons with a higher rate than those in the second
      half of the peptide, consistent with the nuclear magnetic resonance structure of
      this peptide, with amino acids 1-10 being a flexible coil, whereas amino acids 11
      24 are a stable amphipathic helix. The binding interface of KCNQ1 and KCNE1 was
      determined by comparing the difference of sequential fragment ions before and
      after binding. The residues determined to be involved in binding were consistent
      with a cysteine cross-linking study and confirmed by double mutant cycle
      analysis.

PMID- 22392373
TI  - LC-MS/MS fast analysis of androgenic steroids in urine.
AB  - The liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was
      developed and validated to detect androgenic steroids: trenbolone,
      nortestosterone, boldenone, methylboldenone, testosterone, methyltestosterone,
      17beta-1-testosterone and their metabolites in bovine urine. Sample preparation
      before LC-MS/MS analysis involved an enzymatic hydrolysis with glucuronidase AS
      HP, isolation of free hormones from urine on C(18) SPE column and purification of
      the extract using liquid-liquid extraction with n-pentane and SPE NH(2) column.
      For the chromatographic separation of steroids, the Poroshell 120-EC C18 column
      (150 * 2.1 mm, 2.7 MUm) was used. Mass spectrometric measurement was achieved
      using the API 4000 triple quadrupole (QqQ) instrument with a TurboIon-Spray
      source operating in positive electrospray ionization mode. The procedure was
      validated according to the Decision 2002/657/EC. Recovery ranged from 76.5% to
      118.9% for all examined compounds. The repeatability was below 20% and
      reproducibility did not exceed the 25%. The linearity was good for all analytes
      in the whole range of tested concentrations, as proved by the correlation
      coefficients greater than 0.99. The decision limit (CCalpha) ranged from 0.10 to
      0.17 MUg L(-1) for all analytes, whereas the detection capability (CCbeta) ranged
      from 0.17 to 0.29 MUg L(-1). The application of an innovative Poroshell column
      allowed for very good chromatographic separation of steroids with a much shorter
      time of analysis.

PMID- 22392374
TI  - Ambient-ageing processes in amine self-assembled monolayers on microarray slides
      as studied by ToF-SIMS with principal component analysis, XPS, and NEXAFS
      spectroscopy.
AB  - We investigated the ageing of amine-terminated self-assembled monolayers (amine
      SAMs) on different silica substrates due to exposure to different ambient gases,
      pressures, and/or temperatures using time-of-flight secondary ion mass
      spectrometry (ToF-SIMS) with principal component analysis and complementary
      methods of surface analysis as X-ray photoelectron spectroscopy (XPS) and near
      edge X-ray absorption fine structure (NEXAFS). The goal of this study is to
      examine the durability of primary amine groups of amine-SAMs stored in a user
      laboratory prior to being used as supports for biomolecule immobilization and
      other applications. We prepared amine-SAMs on the native oxides of silicon wafers
      and glass slides using 3-aminopropyl triethoxysilane, by using optimized
      conditions such as anhydrous organic solvent and reaction time scale of hours to
      avoid multilayer growth. Selected commercial amine-SAM slides have been
      investigated, too. When the amine-SAMs are exposed to air, oxygen incorporation
      occurs, followed by formation of amide groups. The formation of oxygen species
      due to ageing was proved by ToF-SIMS, XPS, and NEXAFS findings such as CNO(-)
      secondary ion emission at m/z 42, observation of the N 1s HNC=O component peak at
      400.2-400.3 eV in XPS, and, last but not least, by formation of a pi*(HNC=O)
      resonance at 401 eV in the N K-edge X-ray absorption spectrum. It is concluded
      that the used multi-method approach comprising complementary ToF-SIMS, XPS, and
      NEXAFS analyses is well suited for a thorough study of chemical aspects of ageing
      phenomena of amine-SAM surfaces.

PMID- 22392375
TI  - An international assessment of the metrological equivalence of higher-order
      measurement services for creatinine in serum.
AB  - The Consultative committee for amount of substance-metrology in chemistry (CCQM)
      K80 Key Comparison directly assessed the equivalence of many of the world's
      higher-order value-assigned materials (HOVAMs) for creatinine in human serum.
      This 2009 international study compared the certified values and uncertainties of
      the materials using measurements made under repeatability conditions. The study
      evaluated 17 materials submitted by 6 national metrology institutes (NMIs). The
      creatinine quantity in these materials ranged from 3 mg/kg to 57 mg/kg (about 0.3
      mg/dL to 6 mg/dL or 30 nmol/L to 500 nmol/L). All materials were stored and
      prepared according the specifications provided by the participating NMIs. Samples
      were processed and analyzed under repeatability conditions by one analyst using
      isotope-dilution liquid chromatography-mass spectrometry in two measurement
      campaigns. The certified values and repeatability measurements were compared
      using uncertainty-weighted generalized distance regression. The instrumental
      repeatability relative standard deviation was 1.2%. The measurement design
      required assessment of within-unit and between-campaign variability in addition
      to measurement repeatability. At a 95% level of confidence, the certified values
      for all 17 materials agreed to within their assigned uncertainties. CCQM-K80
      demonstrated the metrological equivalence of the currently available HOVAMs for
      creatinine in human serum and of the creatinine measurement services provided by
      the participating NMIs.

PMID- 22392376
TI  - Simultaneous determination of two major snow crab aeroallergens in processing
      plants by use of isotopic dilution tandem mass spectrometry.
AB  - Snow crab is a major fishery in the North Atlantic region. During crab processing
      the proteins are aerosolized and some are responsible for development of
      occupational asthma. Tropomyosin and arginine kinase have recently been reported
      as major snow crab allergens. A liquid chromatographic tandem mass spectrometric
      method has been developed for simultaneous analysis of these two proteins in air
      samples collected from processing plants. These proteins were initially isolated
      then characterized by use of mass spectrometry to determine their primary
      structure and signature peptides. The signature peptides were chemically
      synthesized in light and heavy forms and used as standards for developing the
      multiple-reaction monitoring transitions to monitor allergen levels. A validation
      study was performed; precision and accuracy were 1.8-8% and 91-104%,
      respectively. Replicate air samples were collected on air filters from two crab
      processing plants in Newfoundland and Labrador (NL) and four located in Quebec.
      In NL, measured levels of both tropomyosin and arginine kinase were between 1 and
      20 ng m(-3). In Quebec plants, however, levels were found to be much higher at 2
      2400 ng m(-3). Significant differences were also observed among the plants and
      individual processing workstations. For the first time arginine kinase has been
      detected in its aerosolized form in processing plants. In general, levels of the
      allergens were highest in the butchering and cooking areas; plant design can,
      however, have a significant effect on levels of the allergens.

PMID- 22392377
TI  - Pyrolysis and combustion of tobacco in a cigarette smoking simulator under air
      and nitrogen atmosphere.
AB  - A coupling between a cigarette smoking simulator and a time-of-flight mass
      spectrometer was constructed to allow investigation of tobacco smoke formation
      under simulated burning conditions. The cigarette smoking simulator is designed
      to burn a sample in close approximation to the conditions experienced by a lit
      cigarette. The apparatus also permits conditions outside those of normal
      cigarette burning to be investigated for mechanistic understanding purposes. It
      allows control of parameters such as smouldering and puff temperatures, as well
      as combustion rate and puffing volume. In this study, the system enabled
      examination of the effects of "smoking" a cigarette under a nitrogen atmosphere.
      Time-of-flight mass spectrometry combined with a soft ionisation technique is
      expedient to analyse complex mixtures such as tobacco smoke with a high time
      resolution. The objective of the study was to separate pyrolysis from combustion
      processes to reveal the formation mechanism of several selected toxicants. A
      purposely designed adapter, with no measurable dead volume or memory effects,
      enables the analysis of pyrolysis and combustion gases from tobacco and tobacco
      products (e.g. 3R4F reference cigarette) with minimum aging. The combined system
      demonstrates clear distinctions between smoke composition found under air and
      nitrogen smoking atmospheres based on the corresponding mass spectra and
      visualisations using principal component analysis.

PMID- 22392378
TI  - Infrared spectroscopy in hemodialysis: reagent-free monitoring of patient
      detoxification by infrared spectroscopy.
AB  - A method for monitoring hemodialysis based on quantitative infrared spectroscopic
      determination of the molecules dialyzed from patient blood is reported. The
      measurements are reagent-free and aim at real-time and in-line monitoring of the
      hemodialysis patient. A flow cell using attenuated total reflection infrared
      spectroscopy is coupled downstream of the dialysis filter unit. A calibration
      model has been developed from real hemodialysis samples analyzed by chemical
      reference analysis and from artificially mixed dialysis samples. The infrared
      monitoring of hemodialysis includes quantitative determination of urea as the
      lead substance, as well as glucose, lactate, and creatinine, all at a precision
      only limited by the chemical reference analysis. The flow cell can be fitted to
      all standard hemodialysis systems. Preliminary tests with hemodialysis patients
      have demonstrated that detoxification can be clearly monitored. Furthermore,
      these experiments demonstrate that a wide, real-time control of the patient's
      physiological parameters is possible with this method, which could lead to
      increased patient safety.

PMID- 22392379
TI  - Imaging translocation and transformation of bioavailable selenium by Stanleya
      pinnata with X-ray microscopy.
AB  - Selenium hyperaccumulator Stanleya pinnata, Colorado ecotype, was supplied with
      water-soluble and biologically available selenate or selenite. Selenium
      distribution and tissue speciation were established using X-ray microscopy (micro
      X-ray fluorescence and transmission X-ray microscopy) in two dimensions and three
      dimensions. The results indicate that S. pinnata tolerates, accumulates, and
      volatilizes significant concentrations of selenium when the inorganic form
      supplied is selenite and may possess novel metabolic capacity to differentiate,
      metabolize, and detoxify selenite concentrations surpassing field concentrations.
      The results also indicate that S. pinnata is a feasible candidate to detoxify
      selenium-polluted soil sites, especially locations with topsoil polluted with
      soluble and biologically available selenite.

PMID- 22392382
TI  - Burden of mental disorders based on the World Mental Health surveys.

PMID- 22392383
TI  - The role of the World Psychiatric Association in facilitating development of
      psychiatric publications from low-and middle-income countries.

PMID- 22392384
TI  - Gender parity and drug use: are girls catching up with boys?
AB  - OBJECTIVE: To evaluate the association between gender and use of alcohol,
      tobacco, and other drugs in adolescents aged 10 to 18 years in the municipalities
      of Jacarei and Diadema, Sao Paulo, Brazil. METHODS: A total of 971 adolescents
      completed the Drug Use Screening Inventory (DUSI). RESULTS: In our sample, 55% of
      adolescents were male, 33.8% reported having made use in the previous month of
      alcohol, 13.5% of cigarettes, and 6.4% of illicit drugs. There was no significant
      difference between genders in the use of alcohol, tobacco, and illicit drugs in
      any of the analysis (p > 0.05). The use of alcohol, tobacco, and illicit drugs
      was associated with the city, age, educational level, school failure, and
      relationship with parents (p < 0.05). CONCLUSIONS: Substance abuse among
      adolescents in our sample seems to follow the recent global trend towards the
      equalization of drug use between genders. This result should be taken into
      account by public health professionals in developing policies for this problem.

PMID- 22392385
TI  - Psychometric properties of the sixth version of the Addiction Severity Index (ASI
      6) in Brazil.
AB  - BACKGROUND: There are few research tools in Brazil to assess more broadly the
      alcohol and other drug related problems. OBJECTIVE: To test the psychometric
      properties of ASI in its sixth version (ASI-6). METHODS: A multicenter cross
      sectional study was conducted in four Brazilian state capitals. Four research
      centers interviewed 150 adult inpatients or outpatients, and one research center
      interviewed 140 patients. A total of 740 substance abusers were selected.
      Training and supervision of interviewers were performed to assure the quality of
      dada collected. RESULTS: Most areas of the ASI showed good reliability between
      the instrument and the interviewers, with no statistically significant
      differences between the ASI-6 Summary Scores for Recent Functioning (SS-Rs) of
      both interviews. Cronbach's alpha for ASI-6 subscales ranged from 0.64 to 0.95.
      Correlations between the ASI-6 Alcohol and Drug scores and the concurrent
      instrument (ASSIST) were high (0.72 and 0.89, respectively). There was a
      significant negative correlation between the scores in psychiatric, medical and
      drug areas and the scores of WHOQOL. CONCLUSION: Analysis of the psychometric
      properties of ASI-6 both in outpatients and inpatients in Brazil indicate a good
      reliability and validity of this instrument for the Brazilian culture. The
      development of this instrument in Brazil is an important advancement, which will
      certainly have implications for the prevention, clinical research, and social
      rehabilitation fields.

PMID- 22392386
TI  - Suicide mortality in Sao Gabriel da Cachoeira, a predominantly indigenous
      Brazilian municipality.
AB  - OBJECTIVE: To describe the characteristics and the raw suicide mortality rates
      (RSMR) during the period 2000-2007 in the municipality with the largest
      proportion of self-reported indigenous people in Brazil, Sao Gabriel da Cachoeira
      (SGC), State of Amazonas. METHOD: A retrospective descriptive study was carried
      out using data from the Information Department of the Brazilian Unified Health
      System (DATASUS). We considered suicide the cause of death coded in the records
      as voluntary self-Inflicted injuries according to the International
      Classification of Diseases and Related Health Problems, 10th revision. RESULTS:
      Forty-four suicide cases were registered in this period. The average RSMR was
      16.8 per 100,000 inhabitants (male, 26.6; female, 6.3). The highest rates were
      observed in the age groups 15-24 years and 25-34 years, with RSMR of 43.1 and
      30.2 per 100,000 inhabitants, respectively. Most suicides occurred among
      indigenous people (97.7%), males (81.8%), and unmarried people (70.5%). In most
      cases, deaths occurred at home (86.4%), during weekends (59.1%) and mainly by
      hanging (97.7%). CONCLUSION: Suicide is a significant health and social problem
      in SGC. The suicide profile observed in this municipality was, as a whole, more
      similar to that observed in certain indigenous communities than that found in
      most urban and non-indigenous environments, demonstrating the sociocultural
      specificity of these events in Brazil.

PMID- 22392387
TI  - No association between the HTR1A gene and suicidal behavior: a meta-analysis.
AB  - OBJECTIVE: Dysfunction of serotonin 1A receptors (HTR1A) may play a role in the
      genesis of suicidal behavior. We studied the association between a functional
      polymorphism in the HTR1A gene and suicidal behavior. METHOD: We performed a meta
      analysis of published genetic association studies by searching through Medline,
      PubMed, and Web of Science databases to analyze a possible correlation between
      the rs6295 polymorphism and suicidal behavior in different populations. RESULTS:
      Four studies comprising a total of nine hundred and fifty seven patients with
      suicidal behavior and nine hundred and fifty seven controls were the eligible.
      The G allele of the rs6295 polymorphism may not be associated with suicidal
      behavior (Random-effects model: OR = 1.08; 95% CI: 0.80-1.45; p(Z) = 0.80) in
      presence of heterogeneity (Q = 17.84, df = 4, p = 0.0013). In a second analysis
      that presented no heterogeneity, a negative association was also observed (OR =
      0.94; 95%CI: 0.79-1.13; p(Z) = 0.99). CONCLUSION: To our knowledge, the present
      study is the first meta-analysis searching for a correlation between rs6295 of
      HTR1A and suicidal behavior. Our results showed no association between HTR1A and
      suicidal behavior. However, more studies assessing different populations, as well
      as larger samples, are needed.

PMID- 22392388
TI  - The Brazilian smoker: a survey in the largest cities of Brazil.
AB  - OBJECTIVE: To understand the sociodemographic factors associated with daily
      consumption of cigarettes and pattern of cigarette use among Brazilian smokers.
      METHOD: A cross-sectional study was performed in 2005 involving the 108 largest
      Brazilian cities. Data were collected through interviews with subjects aged 12 to
      65 years in randomly selected households. Based on a questionnaire adapted to the
      Brazilian context, a logistic regression model was used to investigate the
      association between the sociodemographic characteristics of the sample and
      smoking. RESULTS: Of the 7,921 subjects interviewed, 16.4% reported daily use of
      cigarettes. The smoking prevalence was similar between genders, although women
      reported to start smoking at a later age and smoke fewer cigarettes per day.
      Almost 65% of the smokers were interested in quitting or reducing their smoking
      habit. The main sociodemographic characteristics associated with smoking were as
      follows: adult age (30-59 years old), unemployment, low education level, and low
      socioeconomic level. Alcohol abuse was also shown to be associated with smoking.
      CONCLUSIONS: Our findings suggest that adverse socioeconomic characteristics are
      implicated in increased susceptibility to smoking in Brazil. In our sample, a
      high proportion of smokers reported interest to quit or reduce smoking. These
      data suggest that sociodemographic factors should be considered in the
      elaboration of smoking prevention and treatment policies.

PMID- 22392389
TI  - Low family support perception: a 'social marker' of substance dependence?
AB  - OBJECTIVE: Simultaneously assess the relationship between the family support
      perception and the intensity of hopelessness, depression, and anxiety symptoms in
      alcohol or drug dependent (AOD) patients and in non-AOD dependent control group
      (CON). METHOD: 60 patients who met the DSM-IV criteria for AOD dependence and 65
      individuals with similar profile, but not dependent on AOD completed the Family
      Support Perception Inventory (FSPI), Beck Depression Inventory (BDI), Beck
      Anxiety Inventory (BAI), and Beck Hopelessness Scale (BHS). RESULTS: Logistic
      regression analysis indicated that high scores in family autonomy (OR = 0.08),
      and low scores in hopelessness (OR = 0.64) were negatively correlated with AOD
      dependence. Individuals with high scores in BAI had higher probability (OR =
      1.22) of belonging to the AOD group, as well as those who reported previous
      psychiatric treatment (OR = 68.91). Only in the AOD group the total FSPI scores
      presented significant correlation with depression, anxiety, and hopelessness.
      CONCLUSIONS: Individuals with AOD dependence and low scores of family support
      perception also presented high scores of depression, anxiety, and hopelessness,
      suggesting that FSPI scores could be a useful 'social marker' of AOD dependence
      with psychiatric comorbidities. These data also reinforce the relevance of
      evaluating family support in AOD treatment planning.

PMID- 22392390
TI  - Peritraumatic tonic immobility is associated with posttraumatic stress symptoms
      in undergraduate Brazilian students.
AB  - OBJECTIVE: Tonic immobility is a defensive reaction occurring under extreme life
      threats. Patients with posttraumatic stress disorder (PTSD) reporting
      peritraumatic tonic immobility show the most severe symptoms and a poorer
      response to treatment. This study investigated the predictive value of tonic
      immobility for posttraumatic stress symptoms in a non-clinical sample. METHODS:
      One hundred and ninety-eight college students exposed to various life threatening
      events were selected to participate. The Posttraumatic Stress Disorder Checklist 
      Civilian Version (PCL-C) and tonic immobility questions were used. Linear
      regression models were fitted to investigate the association between
      peritraumatic tonic immobility and PCL-C scores. Peritraumatic dissociation,
      peritraumatic panic reactions, negative affect, gender, type of trauma, and time
      since trauma were considered as confounding variables. RESULTS: We found
      significant association between peritraumatic tonic immobility and PTSD symptoms
      in a non-clinical sample exposed to various traumas, even after regression
      controlled for confounding variables (beta = 1.99, p = 0.017). CONCLUSIONS: This
      automatic reaction under extreme life threatening stress, although adaptive for
      defense, may have pathological consequences as implied by its association with
      PTSD symptoms.

PMID- 22392391
TI  - Prevalence and clinical impact of eating disorders in bipolar patients.
AB  - OBJECTIVES: To study the impact of eating disorders (EDs) on the severity of
      bipolar disorder (BD). METHODS: The Structured Clinical Interview for DSM-IV Axis
      I (SCID-I), Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale
      (HAM-D-17), Hamilton Anxiety Rating Scale (HAM-A), Global Assessment of
      Functioning (GAF), Clinical Global Impression (CGI), and the World Health
      Organization Quality of Life Assessment (WHOQOL-BREF) were used. Clinical and
      sociodemographic data were also collected. RESULTS: Among the 356 bipolar
      patients included in this study, 19 (5.3%) were also diagnosed with ED. Of these,
      57.9% had bulimia nervosa (BN) and 42.1% had anorexia nervosa (AN). Among ED
      patients, 94.7% were female. Bipolar patients with EDs presented with lower
      scores in the mental health domain of the WHOQOL-BREF, higher scores of
      depressive symptoms, and more psychiatric comorbidities. CONCLUSIONS: ED
      comorbidities imposed important negative outcomes in bipolar patients. This
      finding suggests that attention should be given to the presence of EDs in BD
      patients and that better treatments focused on this population should be
      developed.

PMID- 22392392
TI  - Peripheral chemokine levels in women with recurrent major depression with
      suicidal ideation.
AB  - OBJECTIVE: To compare serum levels of MCP-1/CCL2, RANTES/CCL5, and Eotaxin/CCL11
      between female patients with recurrent major depressive disorder (MDD) and
      healthy controls, verifying if there is a difference in the levels of these
      mediators between those with or without current suicidal ideation. METHODS:
      Thirty female outpatients with recurrent MDD were divided in two groups
      accordingly the presence or absence of suicidal ideation. These groups were
      compared with 16 healthy controls. Serum levels of MCP-1/CCL2, RANTES/CCL5, and
      Eotaxin/CCL11 were determined. Depression severity was evaluated by Beck
      Depression Inventory (BDI). Suicidal ideation was assessed by SCID-I and BDI.
      RESULTS: Patients with recurrent MDD and healthy controls did not differ in age,
      socioeconomic status, and education. All patients reported high scores of BDI
      (mean, SD, n; 29.75, 10.55, 28). Multivariable analysis of covariance adjusted
      for age and BMI showed that MDD patients with suicidal ideation presented lower
      levels of MCP-1/ CCL2 and RANTES/CCL5 (p < 0.001) and higher levels of
      Eotaxin/CCL11 (p = 0.04) compared to healthy controls. These differences remained
      significant after adjusting for depression severity. CONCLUSION: The findings of
      this study indicated that the presence of recurrent MDD with suicidal ideation is
      associated with differences in inflammatory chemokines when compared to those
      without suicidal ideation.

PMID- 22392393
TI  - Development and validation of the Intrinsic Religiousness Inventory (IRI).
AB  - OBJECTIVE: The role of religious involvement in mental health has been
      increasingly investigated in psychiatric research; however, there is a shortage
      of scales on religiousness in Portuguese. The present study aimed to develop and
      validate a brief instrument to assess intrinsic religiosity (Intrinsic
      Religiousness Inventory - IRI) in two Brazilian samples. METHOD: The initial
      version was based on literature review and experts' suggestions. University
      students (sample 1; n = 323) and psychiatric patients (sample 2; n = 102)
      completed the Duke Religiosity Index (DUREL), the IRI, an instrument of
      spirituality measurement (WHOQOL-SRPB), as well as measurements of anxiety and
      depressive symptoms. RESULTS: The IRI showed adequate internal consistence
      reliability in sample 1 (Cronbach's alpha = 0.96; 95% CI; 0.95-0.97) and sample 2
      (alpha = 0.96; 95% CI; 0.95-0.97). The IRI main component analyses indicated a
      single factor, which explained 73.7% and 74.9% of variance in samples 1 and 2,
      respectively. Strong correlations between IRI and intrinsic subscale of the DUREL
      were observed (Spearman's r ranging from 0.87 to 0.73 in samples 1 and 2,
      respectively, p < 0.001). The IRI showed good test-retest reliability (intraclass
      correlation coefficients > 0.70). CONCLUSION: These data indicate that the IRI is
      a valid instrument and may contribute to study intrinsic religiosity in Brazilian
      samples.

PMID- 22392394
TI  - Molecular medicine: a path towards a personalized medicine.
AB  - Psychiatric disorders are among the most common human illnesses; still, the
      molecular and cellular mechanisms underlying their complex pathophysiology remain
      to be fully elucidated. Over the past 10 years, our group has been investigating
      the molecular abnormalities in major signaling pathways involved in psychiatric
      disorders. Recent evidences obtained by the Instituto Nacional de Ciencia e
      Tecnologia de Medicina Molecular (National Institute of Science and Technology -
      Molecular Medicine, INCT-MM) and others using behavioral analysis of animal
      models provided valuable insights into the underlying molecular alterations
      responsible for many complex neuropsychiatric disorders, suggesting that
      "defects" in critical intracellular signaling pathways have an important role in
      regulating neurodevelopment, as well as in pathophysiology and treatment
      efficacy. Resources from the INCT have allowed us to start doing research in the
      field of molecular imaging. Molecular imaging is a research discipline that
      visualizes, characterizes, and quantifies the biologic processes taking place at
      cellular and molecular levels in humans and other living systems through the
      results of image within the reality of the physiological environment. In order to
      recognize targets, molecular imaging applies specific instruments (e.g., PET)
      that enable visualization and quantification in space and in real-time of signals
      from molecular imaging agents. The objective of molecular medicine is to
      individualize treatment and improve patient care. Thus, molecular imaging is an
      additional tool to achieve our ultimate goal.

PMID- 22392395
TI  - A review on predictors of treatment outcome in social anxiety disorder.
AB  - OBJECTIVE: This article aims to review the clinical features and therapeutic
      characteristics that may predict treatment response in patients with social
      anxiety disorder (SAD). METHODS: A systematic review of trials identified through
      databases of ISI, Medline, PsycInfo, Cochrane, LILACS, Current Controlled Trials,
      and in references of previously selected articles published in English up to
      December 2010. In our literature search, we used the words prediction/predictors
      and social anxiety disorder or social phobia. RESULTS: Early onset, greater
      disease severity, comorbidity with other anxiety disorders (including generalized
      anxiety disorder and simple phobia), and high expectations about the role of the
      therapist emerged as potential predictors of less effective treatment in SAD.
      CONCLUSIONS: Knowledge of various clinical and treatment features may help
      professionals to predict possible responses to therapeutic interventions in
      patients with SAD. However, given the diversity of measures used to assess
      response, further studies should be performed with standardized methods to
      investigate the aspects related to treatment resistance in SAD.

PMID- 22392396
TI  - Neuroimaging in specific phobia disorder: a systematic review of the literature.
AB  - OBJECTIVE: Specific phobia (SP) is characterized by irrational fear associated
      with avoidance of specific stimuli. In recent years, neuroimaging techniques have
      been used in an attempt to better understand the neurobiology of anxiety
      disorders. The objective of this study was to perform a systematic review of
      articles that used neuroimaging techniques to study SP. METHOD: A literature
      search was conducted through electronic databases, using the keywords: imaging,
      neuroimaging, PET, spectroscopy, functional magnetic resonance, structural
      magnetic resonance, SPECT, MRI, DTI, and tractography, combined with simple
      phobia and specific phobia. One-hundred fifteen articles were found, of which 38
      were selected for the present review. From these, 24 used fMRI, 11 used PET, 1
      used SPECT, 2 used structural MRI, and none used spectroscopy. RESULT: The search
      showed that studies in this area were published recently and that the
      neuroanatomic substrate of SP has not yet been consolidated. CONCLUSION: In spite
      of methodological differences among studies, results converge to a greater
      activation in the insula, anterior cingulate cortex, amygdala, and prefrontal and
      orbitofrontal cortex of patients exposed to phobia-related situations compared to
      controls. These findings support the hypotheses of the hyperactivation of a
      neuroanatomic structural network involved in SP.

PMID- 22392397
TI  - Cognitive-behavior therapy-online in OCD patient with hoarding symptoms.

PMID- 22392398
TI  - Hypoplastic splenium of the corpus callosum and co-occurrence of attention
      deficit/hyperactivity and language disorders: a case report.

PMID- 22392399
TI  - Alcohol and other drug use by Brazilian truck drivers: a cause for concern?

PMID- 22392400
TI  - Unfeasibility of a risk mitigation strategy for sibutramine.

PMID- 22392401
TI  - Increased serum levels of C3 and C4 in patients with schizophrenia compared to
      eutymic patients with bipolar disorder and healthy.

PMID- 22392404
TI  - Olive oil intake and breast cancer risk in the Mediterranean countries of the
      European Prospective Investigation into Cancer and Nutrition study.
AB  - Although there is some evidence suggesting that olive oil could reduce breast
      cancer (BC) risk, the epidemiological data are still relatively limited, not
      entirely consistent and mainly based on case-control studies. Therefore, we
      prospectively assessed the association between olive oil and BC risk in
      postmenopausal women from the Mediterranean cohorts within the European
      Prospective Investigation into Cancer and Nutrition. The analysis included 62,284
      postmenopausal women recruited from Spain, Italy and Greece who had complete
      dietary data (collected from validated country-specific dietary questionnaires).
      The risk of BC (overall and by hormone receptor subtypes) was assessed using
      hazards ratios (HRs) obtained from Cox proportional hazards regression, while
      adjusting for known BC risk factors. After a mean follow-up of 9 years, 1,256
      women were diagnosed with a primary incident invasive BC. The multivariate HRs
      for BC risk by olive oil intake (highest vs. lowest tertile of g/day/2,000 kcal)
      were 1.07 (95% CI = 0.91-1.25) in the adjusted model, 1.06 (95% CI = 0.91-1.24)
      in the model additionally adjusted for reproductive-related factors and 1.10 (95%
      CI = 0.92-1.31) for the model additionally adjusted for dietary factors. There
      was no association between olive oil and risk of estrogen or progesterone
      receptor-positive tumors, but a suggestion of a negative association with
      estrogens and progesterone receptor-negative tumors. The results from our
      prospective study showed that olive oil consumption during adult life was not
      associated with the risk of BC. However, larger prospective studies are still
      needed to explore possible differences related to hormone receptor status.

PMID- 22392405
TI  - Errors in fluid therapy in medical wards.
AB  - BACKGROUND: Intravenous fluid therapy remains an essential part of patients' care
      during hospitalization. There are only few studies that focused on fluid therapy
      in the hospitalized patients, and there is not any consensus statement about
      fluid therapy in patients who are hospitalized in medical wards. OBJECTIVE: The
      aim of the present study was to assess intravenous fluid therapy status and
      related errors in the patients during the course of hospitalization in the
      infectious diseases wards of a referral teaching hospital. SETTING: This study
      was conducted in the infectious diseases wards of Imam Khomeini Complex Hospital,
      Tehran, Iran. METHODS: During a retrospective study, data related to intravenous
      fluid therapy were collected by two clinical pharmacists of infectious diseases
      from 2008 to 2010. Intravenous fluid therapy information including indication,
      type, volume and rate of fluid administration was recorded for each patient. An
      internal protocol for intravenous fluid therapy was designed based on literature
      review and available recommendations. The data related to patients' fluid therapy
      were compared with this protocol. The fluid therapy was considered appropriate if
      it was compatible with the protocol regarding indication of intravenous fluid
      therapy, type, electrolyte content and rate of fluid administration. MAIN OUTCOME
      MEASURE: Any mistake in the selection of fluid type, content, volume and rate of
      administration was considered as intravenous fluid therapy errors. RESULTS: Five
      hundred and ninety-six of medication errors were detected during the study period
      in the patients. Overall rate of fluid therapy errors was 1.3 numbers per patient
      during hospitalization. Errors in the rate of fluid administration (29.8%),
      incorrect fluid volume calculation (26.5%) and incorrect type of fluid selection
      (24.6%) were the most common types of errors. The patients' male sex, old age,
      baseline renal diseases, diabetes co-morbidity, and hospitalization due to
      endocarditis, HIV infection and sepsis are predisposing factors for the
      occurrence of fluid therapy errors in the patients. CONCLUSION: Our result showed
      that intravenous fluid therapy errors occurred commonly in the hospitalized
      patients especially in the medical wards. Improvement in knowledge and attention
      of health-care workers about these errors are essential for preventing of
      medication errors in aspect of fluid therapy.

PMID- 22392406
TI  - Balloon dilatation: a helpful technique for removal of a stuck dialysis line.
AB  - We describe a useful technique for the removal of an irretrievable/stuck long
      term intravenous catheter. The alternative would have meant removing it
      surgically or snaring it in a case of extremely difficult venous access. The
      process we used was effective in this particular case.

PMID- 22392407
TI  - Comparison of myofibroblasts expression in oral squamous cell carcinoma,
      verrucous carcinoma, high risk epithelial dysplasia, low risk epithelial
      dysplasia and normal oral mucosa.
AB  - The aim was to evaluate and compare the presence of myofibroblasts in oral
      squamous cell carcinoma (OSCC), verrucous carcinoma (VC), high-risk epithelial
      dysplasia (HRED), low-risk epithelial dysplasia (LRED), and normal oral mucosa
      (NOM). The study consisted of 37 OSCC, 15 VC, 15 HRED, 15 LRED and 15 NOM. alpha
      smooth muscle actin (alpha-SMA) antibody was used to identify myofibroblasts. The
      alpha-SMA expression was not observed in NOM and LRED. The alpha-SMA was
      expressed in 97.29% of OSCC, 86.66% of VC, 46.66 % of HRED. The alpha-SMA
      expression was significantly higher in OSCC than VC (p = 0.023) and HRED (p <
      0.000). The alpha-SMA expression was significantly higher in VC than HRED (p =
      0.043). Myofibroblastic expression, as highlighted by alpha-SMA, is undetectable
      in NOM and LRED but increases as the disease progresses from potentially
      malignant disorders, as HRED to VC to invasive OSCC. Thus, proliferation of
      myofibroblasts may be used as a stromal marker of oral premalignancy and
      malignancy.

PMID- 22392408
TI  - Sinonasal seromucinous hamartoma: a review of the literature and a case report
      with focal myoepithelial cells.
AB  - Seromucinous hamartoma is a benign lesion of the sinonasal tract. Since its
      description in 1974, only a small number of additional cases have been reported.
      It is composed of a proliferation of seromucinous glands and ducts within a
      variable fibrous stroma. The serous component typically stains positively for
      S100 (at least focally) and lacks p63 positive abluminal cells. The lack of
      myoepithelial/basal cells is an important diagnostic feature of seromucinous
      hamartoma; their absence could lead to an incorrect diagnosis of low-grade
      sinonasal adenocarcinoma. We report the case of a polypoid mass resected from the
      posterior nasal cavity and nasopharynx of a 54-year-old woman. The lesion
      contained a population of small and large glands lined by cuboidal to flattened
      cells within a hypocellular stroma varying from dense and sclerotic to myxoid.
      Additionally, there was a superficial focus of ciliated invaginated surface
      epithelium and glands. Throughout the lesion there were no cytologic or
      architectural features of malignancy. The histologic features were diagnostic of
      seromucinous hamartoma. Immunohistochemistry showed focal S100 positivity of the
      serous glands. However, in contrast to previously reported cases, the glands
      focally showed an outer basal layer that was calponin, p63 and actin positive.
      Our case demonstrates two important points. First, complete absence of p63
      staining should not necessarily be a required feature in the diagnosis of
      seromucinous hamartoma. Second, the ciliated larger glands--in keeping with
      respiratory epithelial adenomatoid hamartoma (REAH)--support the suggestion that
      seromucinous hamartoma and REAH are a spectrum of lesions, often seen together.

PMID- 22392409
TI  - Evaluation of PTEN immunoexpression in oral submucous fibrosis: role in
      pathogenesis and malignant transformation.
AB  - Oral submucous fibrosis (OSMF) is a chronic debilitating disease and a
      premalignant condition of the oral cavity characterized by generalized submucosal
      fibrosis. Despite its precancerous nature, the molecular biology regarding its
      malignant potential has not been extensively studied. PTEN, a known tumor
      suppressor gene is mutated in a majority of human cancers and has also been
      implicated in several fibrotic disorders. The present study aims to evaluate the
      expression of PTEN in OSMF and oral squamous cell carcinoma (OSCC) and correlate
      it with the pathogenesis and malignant transformation of OSMF. 60 cases total of
      OSMF (30) and OSCC (30) were subjected to immunohistochemistry using PTEN
      antibody. Ten normal oral mucosa (NOM) specimens were also stained as controls.
      There was progressive loss of PTEN expression from normal mucosa to OSMF and OSCC
      (p <= 0.001). Significant differences were observed for PTEN expression between
      NOM and OSMF, OSMF and OSCC as well as NOM and OSCC. Though a progressive loss of
      PTEN was noticed between early OSMF and advanced OSMF, the variation did not
      reach statistical significance (p >= 0.001). Data suggest that there is a
      significant loss of PTEN expression in OSMF as compared to normal oral mucosa and
      that this trend increased from OSMF to OSCC. Thus, alteration of PTEN is likely
      an important molecular event in OSMF pathogenesis and oral carcinogenesis.

PMID- 22392410
TI  - Bilateral buccal bifurcation cyst: case report and literature review.
AB  - Buccal bifurcation cyst (BBC) is a rare inflammatory odontogenic cyst that
      typically occurs at the buccal region of the first or second mandibular molars of
      children. In the current case, a 9-year-old boy complained of an extraoral soft
      tissue painful swelling. Intraoral examination revealed a partial eruption of the
      right permanent mandibular first molar with drainage of purulent material and
      clinical absence of the left mandibular first molar. Panoramic radiographic and
      computed tomography showed two well-defined areas surrounding the mandibular
      first molars consistent with cystic lesions. Surgical enucleations were performed
      and histopathologic analysis revealed inflammatory cysts. Based on the clinical,
      microscopic, radiographic, and CT images, the diagnosis of bilateral BBC was
      established. Patient has been under follow-up for about 1 year showing normal
      bone repair and eruption of the involved teeth. Although BBC is uncommon, it is
      important to recognize this entity.

PMID- 22392411
TI  - Characterisation of surface wettability based on nanoparticles.
AB  - Nanoparticles are becoming frequently used in the research area of creating
      functional surfaces because they can be more versatile than just making
      dimensions smaller. Particularly, a variety of nanoparticles have been applied
      for the construction of superhydrophobic and superhydrophilic surfaces with micro
      and nano-scaled structures. As nanoparticles can also be fashioned and modified,
      their effects will be of great importance to the formed surface structures. In
      the present paper, we review the recent research progress in the utilization of
      nanoparticles to form extremely wettable/non-wettable surface structures and
      their influence on surface wettability. This report manifests an apparent
      inclination of nanoparticle structured surfaces using the multidisciplinary
      approaches, from the viewpoint of engineer/scientist. Therefore, the typical
      methodologies with regard to the use of nanoparticles, including the preparation
      and functionalisation processes, for the realization of surface wettabilities are
      discussed in this work. The discussions also represent some of the size
      determined phenomena that are related to wettable/non-wettable surfaces. This
      Review thus provides an insight into the connection between nanoparticles and
      surface wettability.

PMID- 22392412
TI  - Perceived competence and depressive symptoms among adolescents: the moderating
      role of attributional style.
AB  - This longitudinal study examined the interactive effects of depressive
      attributional style and multiple domains of perceived competence on depressive
      symptoms among 431 adolescents. Our structural equation modeling with latent
      factor interactions indicated that (1) for girls with a higher depressive
      attributional style, lower perceived competence in physical appearance was
      predictive of depressive symptoms over a 2.5 year period, and (2) regardless of
      gender, among adolescents with a higher depressive attributional style, lower
      athletic competence was predictive of higher depressive symptoms 6 months later,
      which in turn were related to higher depressive symptoms 2 years later.
      Significant main effects suggested that lower levels of perceived social
      acceptance were associated with higher subsequent levels of depressive symptoms
      but only for boys. These findings have implications for understanding the roles
      of perceived competence and attributional style in predicting depressive symptoms
      among adolescent girls and boys.

PMID- 22392413
TI  - Relations between parent psychopathology, family functioning, and adolescent
      problems in substance-abusing families: disaggregating the effects of parent
      gender.
AB  - The present study: (1) examined relations between parent psychopathology and
      adolescent internalizing problems, externalizing problems, and substance use in
      substance-abusing families; and (2) tested family functioning problems as
      mediators of these relations. Structural equation modeling was used to estimate
      the independent effects of parent psychopathology and family functioning problems
      by parent gender. Participants included 242 parents in treatment for substance
      abuse and/or dependence and 59 of their coparents (16.9% in treatment for
      substance-abuse/dependence) from middle income households (SES: M = 4.7; SD =
      2.1). Ratings were obtained for 325 adolescents (48% female; 27.8% non-Caucasian)
      between the ages of 10 and 18 years (M = 13.5 years; SD = 2.5 years). Parent
      psychopathology, family functioning problems, and adolescent problems were
      assessed with parent and coparent ratings on the Symptom Checklist (SCL-90)/Brief
      Symptom Inventory (BSI), the Family Relationship Measure, and the Child Behavior
      Checklist, respectively. Results indicated that maternal psychopathology was
      directly related to adolescent internalizing problems and substance use, but
      maternal perceptions of family functioning problems failed to mediate relations
      between maternal psychopathology and adolescent problems. By contrast, paternal
      perceptions of family functioning problems uniquely mediated relations between
      paternal psychopathology and adolescent externalizing problems. Findings
      underscore the importance of examining how mothers and fathers may differentially
      impact adolescent problems in substance-abusing families.

PMID- 22392414
TI  - The contribution of parenting practices and parent emotion factors in children at
      risk for disruptive behavior disorders.
AB  - The goal of this study was to examine the impact of different parenting
      characteristics on child disruptive behavior and emotional regulation among a
      sample of at-risk children. The sample consisted of 373 Australian 5- to 9-year
      old children who were screened for serious behavior problems. Seven parenting
      variables based on self-report were evaluated, involving parenting practices,
      emotion beliefs and behaviors, emotion expressiveness, and mental health. Outcome
      variables based on parent/teacher report were child disruptive behavior problems
      and emotion regulatory ability. When entered simultaneously in a multiple
      regression analysis, inconsistent discipline, negative parental emotional
      expressiveness, and parent mental health demonstrated the strongest relationship
      to disruptive behavior problems and problems with emotion regulation. The data
      presented here elucidate multiple risk pathways to disruptive behavior disorders
      and can inform the design of prevention and early intervention programs.

PMID- 22392415
TI  - A double-blind placebo controlled trial of Ginkgo biloba added to risperidone in
      patients with autistic disorders.
AB  - Ginkgo biloba has been reported to affect the neurotransmitter system and to have
      antioxidant properties that could impact the pathogenesis of Autism Spectrum
      Disorder. Based on these studies, we decided to assess the effectiveness of
      Ginkgo biloba extract (Ginko T.D., Tolidaru, Iran) as an adjunctive agent to
      risperidone in the treatment of autism. Forty-seven outpatients with a DSM-IV-TR
      diagnosis of autism ages between 4 and 12 years were assigned to this double
      blinded clinical trial and were randomly divided into two groups. One group
      received risperidone plus Ginko T.D and the other received risperidone plus
      placebo. The dose of risperidone was 1-3 mg/day and the dose of Ginko T.D. was 80
      mg/day for patients under 30 kg and 120 mg/day for patients above 30 kg. Patients
      were assessed using Aberrant Behavior Checklist-Community (ABC-C) rating scale
      and the side effect check list every 2 weeks until the endpoint. None of the 5
      subscales of ABC-C rating scale showed significant differences between the two
      groups. Incidents of side effects were not significantly different between the
      two groups. Adding Ginkgo biloba to risperidone did not affect the treatment
      outcome of ADs. Nevertheless, further observations are needed to confirm this
      result.

PMID- 22392416
TI  - Parental and late adolescent psychopathology: mothers may provide support when
      needed most.
AB  - Research links negative parenting and parental psychopathology to poorer outcomes
      among youth. Less research examines these effects simultaneously during late
      adolescence. The current study examines parenting, parental psychopathology, and
      late adolescent psychopathology as reported by late adolescents (N = 328) with
      the use of structural equation modeling. Results of measurement models indicate
      that parental psychopathology and parenting are related to late adolescent
      psychopathology. However, results of structural models indicate that the effect
      of parenting on late adolescent psychopathology becomes non-significant in the
      paternal model and reverses in the maternal model. Interestingly, maternal
      parenting is associated with higher levels of late adolescent psychopathology,
      suggesting that mothers provide their late adolescents with more supportive
      parenting when it is needed most. Overall, results suggest the importance of
      examining parenting characteristics simultaneously in the context of gender and
      other variables.

PMID- 22392417
TI  - Pharmacy school provenance and pharmacy practice.

PMID- 22392418
TI  - On pharmacogenomics in pharmacy benefit management.
AB  - Recently, the separate trajectories of pharmacy benefit management and
      pharmacogenomics converged. Pharmacogenomic tests have become more widely
      available for clinical use and at costs within the range of typical health care
      services. Pharmacy benefit payers continue to seek the precision they can apply
      to their coverage policies and clinical programs that pharmacogenomics offers. We
      describe how pharmacogenomics can now make sense as part of a pharmacy benefit
      and also how pharmacogenomics can be applied in a benefit coverage policy and
      clinical programs. Detail is provided on clinical program development and
      implementation processes featuring pharmacogenomics. We also discuss the research
      needed to support ongoing program development involving pharmacogenomics and
      describe the current roles of benefit payers and administrators in these research
      efforts. The legal and ethical dimensions of applying pharmacogenomics in
      pharmacy benefits are covered and in particular how benefit payers and
      administrators need to navigate between genetic exceptionalism and applicable
      laws and regulations. Finally, some thoughts are provided on future opportunities
      and challenges for pharmacogenomics in pharmacy benefit management and pharmacy
      in general.

PMID- 22392419
TI  - Sustained impact of anticoagulant control achieved in an anticoagulation
      management service after transfer of management to the primary care physician.
AB  - STUDY OBJECTIVES: To determine whether the impact of anticoagulant control
      achieved in an Anticoagulation Management Service (AMS) is sustained after
      transfer of anticoagulation management to the primary care physician (PCP), and
      to assess patient satisfaction with their anticoagulation management by both the
      AMS and PCP. DESIGN: Prospective, randomized trial. SETTING: Pharmacist-directed
      ambulatory AMS located in a tertiary medical care facility and PCP practices in
      Canada. PATIENTS: Sixty-two adults who had received at least 6 months of warfarin
      therapy managed by the AMS. INTERVENTION: Patients were randomly assigned to
      remain with AMS care (32 patients) or to transfer their anticoagulation
      management care to their PCP (30 patients). After 4.5 months of care, patients in
      both groups completed a validated survey instrument assessing their satisfaction
      with the management of their warfarin therapy. MEASUREMENTS AND MAIN RESULTS: Of
      295 patients screened, most were excluded from the study for denying consent or
      for having previous bleeding or clotting complications while taking warfarin.
      Patients in the AMS and PCP groups who completed the study were similar in age
      (median 70 and 76 yrs, respectively), and most had atrial fibrillation as an
      indication for warfarin (75% and 83%, respectively). The primary outcome measure
      mean percentage of time within the desired international normalized ratio (INR)
      range after 6 months-was compared between the two groups, using both the actual
      range (INR 2.5 +/- 0.5) and an expanded range (INR 2.5 +/- 0.7). No significant
      difference was noted in this outcome between the groups (73.5 +/- 19.1% vs 76.9
      +/- 24.5% for the AMS vs PCP groups, p=0.54). Other outcome measures were rates
      of thrombotic and hemorrhagic events resulting in emergency department visits or
      hospitalizations, patients' overall satisfaction with warfarin therapy, and
      patients' preferred anticoagulation management strategy. Two hemorrhagic events
      and one thrombotic event occurred in each group. Patients were more satisfied
      with their anticoagulant management by the AMS relative to PCP care (p=0.01), and
      given the choice, patients preferred AMS care (p=0.001). CONCLUSION: During this
      6-month trial, anticoagulation control did not significantly differ between
      patients who continued to receive anticoagulation management by the AMS and those
      who transferred to their PCP for anticoagulation management, indicating that the
      effects of AMS care were sustained. Although patients were more satisfied and
      preferred to stay with AMS care, this study shows that select patients could have
      their anticoagulation care transferred to their PCP without compromising
      anticoagulation control.

PMID- 22392420
TI  - Economic analysis of alvimopan for prevention and management of postoperative
      ileus.
AB  - STUDY OBJECTIVE: To determine whether alvimopan for prevention of postoperative
      ileus in patients undergoing small- or large-bowel resection by laparotomy is
      associated with lower total costs compared with standard care. DESIGN:
      Pharmacoeconomic analysis using a formal decision model. DATA SOURCE: Four phase
      III clinical trials, two pooled analyses, and one meta-analysis. PATIENT
      POPULATION: A cohort of patients who underwent bowel resection with primary
      anastomosis by laparotomy and received either standardized, accelerated
      postoperative care (usual care) or usual care plus alvimopan. MEASUREMENTS AND
      MAIN RESULTS: Clinical outcomes, obtained from pooled analyses of published
      studies, were time to discharge order written, postoperative nasogastric tube
      insertion, postoperative ileus-related readmission within 7 days, and occurrence
      of nausea and vomiting. Cost inputs included drugs, nursing labor, readmissions,
      and hospitalizations. Costs were assessed by determining the net cost of
      alvimopan use and subsequent reduction in length of stay. Sensitivity and
      scenario analyses were conducted. Costs for alvimopan were $570 based on an
      average of 9.5 doses. Given the 18.4-hour mean reduction in time to discharge
      order written, use of alvimopan reduced hospitalization costs by $2021. Mean
      difference in overall cost of care, as determined by Monte Carlo simulation, was
      $1168 (95% certainty interval -$437 to $5879), favoring the use of alvimopan. In
      the sensitivity analysis, association of alvimopan with lower costs was robust to
      several changes in key parameters including cost and number of doses of
      alvimopan, time to discharge order written, readmission rates, and
      hospitalization cost. In the scenario analyses, alvimopan use yielded a net cost
      of $226 when no difference in time to discharge order written was assumed. In the
      scenario analysis using data from a study that did not enforce opioid use,
      alvimopan resulted in a cost saving of $65/patient. CONCLUSION: Alvimopan was
      cost saving for prevention of postoperative ileus in patients undergoing bowel
      resection by laparotomy, although these potential cost savings were highly
      dependent on a difference in time to discharge order written. This finding is not
      applicable to the less-invasive laparoscopic surgical approach for which quality
      data on alvimopan use are lacking. Limitations of this analysis included use of
      time to discharge order written as a proxy for length of stay and difficulty
      interpreting study results due to inconsistent reporting and conduct of the
      clinical trials evaluating alvimopan. More research is needed to determine the
      cost-effectiveness of alvimopan.

PMID- 22392421
TI  - A real-world evaluation of oral vancomycin for severe Clostridium difficile
      infection: implications for antibiotic stewardship programs.
AB  - STUDY OBJECTIVE: To assess antibiotic treatment patterns and clinical outcomes of
      patients with Clostridium difficile infection (CDI) based on underlying severity
      of CDI disease. DESIGN: Retrospective analysis of data from a prospective cohort
      study. SETTING: Large tertiary care university hospital. PATIENTS: One hundred
      forty-four patients (mean +/- SD age 63 +/- 17 yrs) with CDI who received
      metronidazole (intravenous or oral) or oral vancomycin as their initial therapy
      option between 2006 and 2008. MEASUREMENTS AND MAIN RESULTS: Patients were
      stratified by severity of illness and treatment, and outcomes assessed were
      clinical response, relapse of disease, all-cause inpatient mortality, and length
      of hospital stay. Mild-moderate CDI disease was present in 85 patients (59%) and
      severe disease in 59 patients (41%). Overall, oral vancomycin was given to 16
      patients (11%); use of this drug did not differ according to severity of
      infection. Among patients with severe disease, clinical success occurred in 32
      (63%) of 51 patients given metronidazole and in all 8 patients (100%) given
      vancomycin (p=0.04). Inpatient mortality and hospital length of stay were lower
      in patients with severe CDI who were given oral vancomycin, although these
      results were not statistically significant. CONCLUSION: Oral vancomycin was not
      commonly used for severe CDI. An improved clinical response rate was observed in
      patients with severe CDI given oral vancomycin; this outcome supported results
      from clinical trials. Antibiotic stewardship teams could play a major role in
      providing guidance on CDI treatment based on severity.

PMID- 22392422
TI  - Prescription ergocalciferol dosing for vitamin D repletion: a retrospective
      evaluation.
AB  - STUDY OBJECTIVES: To determine the efficacy and safety of vitamin D repletion
      with prescription ergocalciferol and to determine patient-specific factors that
      may influence the amount of ergocalciferol needed to attain vitamin D
      sufficiency. DESIGN: Retrospective medical record review. SETTING: University
      affiliated outpatient health system. PATIENTS: A total of 1446 patients aged 18
      89 years who had a prescription for ergocalciferol 50,000 IU between January 1,
      2007, and December 31, 2008, were identified; of these patients, 582 patients had
      a vitamin D concentration measured 120 days before their first prescription
      (baseline) and had another concentration measured 60-180 days after this
      prescription (follow-up) and were deemed "first-time users" of ergocalciferol.
      MEASUREMENTS AND MAIN RESULTS: Vitamin D sufficiency was defined as a 25
      hydroxyvitamin D (vitamin D) concentration of 30 ng/ml or higher. Twenty-nine
      different ergocalciferol prescribing regimens were identified in the 1446
      patients. For the 582 first-time users of ergocalciferol, vitamin D
      concentrations increased from a mean +/- SE of 17.7 +/- 0.32 ng/ml at baseline to
      32.9 +/- 0.73 ng/ml at first follow-up concentration, with a mean +/- SE
      prescribed ergocalciferol dose of 63,876 +/- 1973 IU given over an average of 17
      weeks. Overall, 326 (56%) of the 582 first-time users attained sufficiency with
      their prescribed regimen. With use of a logistic regression model to control for
      variables that could influence a patient's response to vitamin D, patients
      prescribed 50,000-100,000 IU/week were significantly more likely to attain
      vitamin D sufficiency compared with those prescribed less than 50,000 IU/week (OR
      2.61, 95% CI 1.37-4.99). Body mass index of 30 kg/m(2)  or higher decreased the
      odds of attaining vitamin D sufficiency, whereas use of a loading dose did not
      increase the odds of attaining sufficiency. CONCLUSION: Many different
      ergocalciferol regimens were used to replace vitamin D, and overall attainment of
      vitamin D sufficiency appeared to be moderate. Based on our findings, an
      ergocalciferol regimen of 50,000-100,000 IU/week with no loading dose could be
      considered as a starting point for vitamin D repletion.

PMID- 22392424
TI  - Selection of the initial methadone regimen for the management of iatrogenic
      opioid abstinence syndrome in critically ill children.
AB  - Iatrogenic opioid abstinence syndrome (IOAS) is a common complication in
      critically ill infants and children receiving prolonged exposure to continuous
      infusions of opioids. Although no guidelines are available regarding management
      of IOAS in children, several treatment options are available, including
      clonidine, morphine, and methadone. Methadone is commonly prescribed due to its
      long half-life and antagonism of the N-methyl-d-aspartate receptor. Different
      approaches, such as weight-based and formula-based methods, have been used to
      determine the initial methadone dosing regimen. Because of the vast differences
      in the recommended dosing regimen from these sources, we conducted a literature
      search to identify articles evaluating the initial methadone dosing regimen for
      prevention and/or treatment of IOAS in children. Specifically, we evaluated the
      reported frequency of withdrawal and oversedation after initiation of methadone
      treatment. Our literature search was limited to English-language articles in the
      MEDLINE (1950-March 2011), EMBASE (1988-March 2011), International Pharmaceutical
      Abstracts (1970-March 2011), and Cochrane Library (1996-March 2011) databases.
      Relevant abstracts and reference citations were also reviewed. A total of eight
      reports representing 183 patients were included in the analysis. There was wide
      discrepancy in the initial methadone dosing regimen. Approximately one-third of
      all patients experienced withdrawal after starting methadone, and there did not
      appear to be a difference between weight-based and formula-based regimens. Seven
      patients experienced oversedation; however, not all articles reported this
      complication. It appears that a standard approach to initial methadone dosing
      does not exist because withdrawal occurred despite the regimen started.
      Therefore, it seems best to begin with the lowest dose possible and titrate to
      the child's response to avoid complications such as oversedation. Routine
      monitoring should be performed in all patients to guide clinicians in the
      management of IOAS.

PMID- 22392423
TI  - Acceptable plasma concentrations of raltegravir and etravirine when administered
      by gastrostomy tube in a patient with advanced multidrug-resistant human
      immunodeficiency virus infection.
AB  - STUDY OBJECTIVE: To determine whether the absorption of four antiretroviral
      agents-raltegravir, etravirine, emtricitabine, and tenofovir-is compromised when
      administered by gastrostomy tube. DESIGN: Pharmacokinetic analysis. SETTING:
      University medical center. PATIENT: A 52-year-old African-American man coinfected
      with advanced multidrug-resistant human immunodeficiency virus (HIV) and chronic
      hepatitis B, who was receiving treatment with raltegravir, etravirine,
      emtricitabine, and tenofovir, and developed ulcerative esophagitis with
      perforation, requiring a gastrostomy tube. MEASUREMENTS AND MAIN RESULTS: Due to
      the patient's esophageal perforations, all nutrition and drug therapy had to be
      provided by gastrostomy tube. As his antiretroviral regimen of raltegravir,
      etravirine, and emtricitabine-tenofovir was not available in liquid or powder
      formulations, the oral tablets were crushed or dispersed and mixed with water,
      then administered by gastrostomy tube. To ensure that the absorption of the drugs
      was sufficient for antiretroviral response, plasma samples were collected at 2
      hours and 12 hours after dosing, and drug concentrations were quantitated by
      using validated assays. The 2- and 12-hour postdose plasma concentrations were
      1220 and 446 ng/ml for raltegravir, 212 and 274 ng/ml for etravirine, 1148 and
      164 ng/ml for emtricitabine, and 320 and 94 ng/ml for tenofovir, respectively.
      The patient's plasma concentrations were then compared with those in published
      pharmacokinetic studies of oral regimens administered to HIV-infected persons and
      healthy volunteers. Overall, the plasma concentrations of the antiretrovirals
      administered by gastrostomy tube were similar to published values. No drug
      toxicities were observed in this patient. CONCLUSION: These pharmacokinetic data
      suggest that absorption of raltegravir, etravirine, emtricitabine, and tenofovir
      was not compromised when the drugs were administered by gastrostomy tube. These
      findings provide a basis for further investigation of the pharmacokinetics,
      safety, tolerance, and antiretroviral response to raltegravir, etravirine, and
      emtricitabine-tenofovir when the oral route of administration is not possible.

PMID- 22392425
TI  - Clinical controversies in thrombolytic therapy for the management of acute
      pulmonary embolism.
AB  - Acute pulmonary embolism is a common complication in hospitalized patients,
      spanning multiple patient populations and crossing various therapeutic
      disciplines. Due to the heterogeneous clinical manifestations, the selection of
      management strategies for patients with acute pulmonary embolism is a challenge
      for clinicians, and a nuanced understanding of the relevant literature is
      required. Previous studies that evaluated thrombolytic therapy in patients with
      acute pulmonary embolism are limited and controversial. Thus, we sought to
      identify the clinical controversies related to thrombolytic therapy in acute
      pulmonary embolism and reviewed the recent literature that impacts clinical
      practice. To apply these controversies into daily clinical practice and decision
      making, we provide an overview of risk stratification and assessment of pulmonary
      embolism. Specific areas of controversies that are discussed relate to the impact
      of thrombolytic therapy on outcomes, specifically in submassive pulmonary
      embolism, including mortality, composite primary end points, and intensive care
      unit length of stay. Other controversies relate to the impact of the patient's
      sex on outcomes, the most safe and effective thrombolytic dose, optimal
      administration techniques including infusion duration or concurrent
      anticoagulation, and therapeutic strategies when thrombolytic therapy is
      unsuccessful. Despite published guidelines and review articles, select aspects of
      thrombolytic therapy for the management of pulmonary embolism remain
      controversial; therefore, clinical practice varies from institution to
      institution and from practitioner to practitioner. When making decisions about
      the role of thrombolytic therapy in patients with pulmonary embolism, clinicians
      must be knowledgeable about areas with limited evidence and the therapy's
      associated risks. In every situation, practitioners must consider the trajectory
      of the patient's status and the ability to intervene in an appropriate time
      frame.

PMID- 22392426
TI  - Boceprevir: a novel NS3/4 protease inhibitor for the treatment of hepatitis C.
AB  - Hepatitis C virus (HCV) infection affects over 170 million people worldwide and
      is the most common blood-borne infection in the United States. Standard treatment
      with peginterferon alfa-ribavirin results in low sustained virologic response
      (SVR) rates in many patients, especially those who are African-American, are
      coinfected with human immunodeficiency virus (HIV), or have liver cirrhosis.
      Because of suboptimal SVR rates, new direct-acting antiviral agents that target
      HCV viral replication steps are in development. Boceprevir is one of the novel
      NS3/4A protease inhibitors that was recently approved by the U.S. Food and Drug
      Administration. We evaluated the literature regarding boceprevir by performing a
      MEDLINE search (January 1996-July 2011) to identify relevant clinical trials.
      Abstracts and poster and oral presentations from hepatology and HIV conferences
      were also reviewed. Potent anti-HCV activity was seen in clinical trials with
      boceprevir when it was studied in HCV genotype 1-infected patients who were naive
      to or had experience with HCV therapy. Data with boceprevir in HIV-HCV-coinfected
      patients are currently lacking; however, initial data on drug-drug interactions
      between boceprevir and antiretrovirals have become available. Resistance to
      boceprevir has been evaluated in trials as well, although more data are needed in
      this area. The most common adverse events with boceprevir included anemia and
      dysgeusia. Based on available data, boceprevir is one of the promising novel
      direct-acting antiviral agents that will likely reshape the treatment of patients
      with HCV infection.

PMID- 22392427
TI  - Palpable purpura complicated by streptococcal toxic shock syndrome resulting in
      limb necrosis and amputation: a case of levamisole and cocaine coingestion.
AB  - Palpable purpura resulting from cocaine and levamisole coingestion has been
      reported with increasing frequency over the last several years as distribution of
      this drug combination becomes more universal. Toxicity from ingestion of this
      dangerous combination is difficult to diagnose due to the multitude of possible
      clinical presentations, variety of possible adulterants, and elusive nature of
      levamisole given its short half-life and limited availability of detection
      methods. Levamisole is a chemotherapeutic and immunomodulatory agent currently
      marketed as a veterinary anthelmintic. We describe the case of a 48-year-old
      woman admitted to our intensive care unit with a diagnosis of streptococcal toxic
      shock syndrome (STSS), confirmed from fluid taken from an elbow lesion that grew
      Streptococcus pyogenes. She was noted to have bullae of the elbow and diffuse
      purpura with necrotic centers covering a large portion of her body (trunk, legs,
      arms, back, toes, fingers, and tip of nose). On further evaluation, she was found
      to have ingested levamisole-tainted cocaine. The patient's complications related
      to either cocaine and levamisole coingestion or STSS included thrombocytopenia,
      acute renal failure, and limb necrosis. Thrombocytopenia gradually improved upon
      treatment with prednisone, and acute renal failure improved with intravenous
      fluid resuscitation; however, she subsequently required several appendage
      amputations due to severe gangrene. Clinicians must have high suspicion for
      ingestion of this drug combination and request prompt testing of urine samples
      for levamisole if a patient who admits to illicit drug use presents with purpuric
      or necrotic skin lesions.

PMID- 22392428
TI  - Prasugrel as a safe alternative for clopidogrel-induced polyarthralgias.
AB  - Clopidogrel is an oral thienopyridine that has been shown to reduce the risk of
      vascular death in patients with acute coronary syndrome, ischemic stroke, and
      peripheral vascular disease. The drug is associated with rare adverse effects
      such as thrombotic thrombocytopenia purpura, acute hepatotoxicity, and
      neutropenia. Only six cases have been reported that link acute arthritis with the
      use of clopidogrel. We describe a 64-year-old Caucasian man with sudden onset of
      severe arthritis, erythema, and swelling after starting clopidogrel therapy; he
      had no history of arthralgias while taking prasugrel during the previous 8
      months. The patient was hospitalized for 3 days, and after cessation of
      clopidogrel therapy and conservative management, he improved dramatically,
      showing resolution of his joint erythema and swelling. The patient started
      prasugrel therapy at discharge, and no arthritic development was noted 8 weeks
      later. Although clopidogrel is commonly well tolerated, this case report
      demonstrates that clinicians should be aware that acute arthritis may be a
      possible adverse effect of clopidogrel. Additionally, polyarthralgias may not be
      a class effect of thienopyridines; patients who experience acute arthralgias
      during clopidogrel therapy may not experience similar adverse effects with
      prasugrel.

PMID- 22392429
TI  - Irreversible atorvastatin-associated hearing loss.
AB  - Drug-associated ototoxicity is a potentially irreversible adverse event. Among
      the several 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins)
      available in the United States, only atorvastatin is associated with tinnitus,
      but none are associated with any forms of hearing loss. A search of the published
      literature (1950-August 2011) revealed no published case reports of ototoxicity
      associated with statins. To our knowledge, we describe the first case of
      progressive, irreversible hearing loss in a 32-year-old man 18 months after
      starting atorvastatin therapy. He began taking atorvastatin 20 mg every evening
      for treatment of hypercholesterolemia. Six months later, he complained of
      occasional episodes of tinnitus, which resolved spontaneously. An audiogram was
      obtained and was normal. By 18 months, the tinnitus became continuous. Another
      audiogram revealed bilateral "cookie-bite" middle-frequency hearing loss.
      Atorvastatin was immediately discontinued, and the patient was fitted with
      hearing aids. Four years after drug discontinuation, his hearing loss had neither
      progressed nor regressed. Use of the Naranjo adverse drug reaction probability
      scale indicated a possible (score of 2) temporal and causal relationship between
      the patient's hearing loss and atorvastatin. Causes of "cookie-bite" hearing loss
      include chronic exposure to loud noises, presbycusis, genetic predisposition, and
      drugs. The manufacturer of atorvastatin has received three unpublished cases of
      deafness, but claims that causal relationships were not established. Despite
      these claims by the manufacturer, based on this case report, we recommend that
      clinicians and patients be aware of the risk of atorvastatin-associated tinnitus
      and permanent hearing loss. Further research is needed to better understand the
      mechanism and frequency of this adverse event.

PMID- 22392430
TI  - Acute care clinical pharmacy practice: unit- versus service-based models.
AB  - This commentary from the 2010 Task Force on Acute Care Practice Model of the
      American College of Clinical Pharmacy was developed to compare and contrast the
      "unit-based" and "service-based" orientation of the clinical pharmacist within an
      acute care pharmacy practice model and to offer an informed opinion concerning
      which should be preferred. The clinical pharmacy practice model must facilitate
      patient-centered care and therefore must position the pharmacist to be an active
      member of the interprofessional team focused on providing high-quality
      pharmaceutical care to the patient. Although both models may have advantages and
      disadvantages, the most important distinction pertains to the patient care role
      of the clinical pharmacist. The unit-based pharmacist is often in a position of
      reacting to an established order or decision and frequently is focused on task
      oriented clinical services. By definition, the service-based clinical pharmacist
      functions as a member of the interprofessional team. As a team member, the
      pharmacist proactively contributes to the decision-making process and the
      development of patient-centered care plans. The service-based orientation of the
      pharmacist is consistent with both the practice vision embraced by ACCP and its
      definition of clinical pharmacy. The task force strongly recommends that
      institutions pursue a service-based pharmacy practice model to optimally deploy
      their clinical pharmacists. Those who elect to adopt this recommendation will
      face challenges in overcoming several resource, technologic, regulatory, and
      accreditation barriers. However, such challenges must be confronted if clinical
      pharmacists are to contribute fully to achieving optimal patient outcomes.

PMID- 22392431
TI  - Binding of rhodamine B and kiton red S to cucurbit[7]uril: density functional
      investigations.
AB  - The binding of the laser dyes rhodamine B (RhB) and sulforhodamine B (kiton red S
      or KRS) to a cucurbit[7]uril (CB[7]) host has been investigated using density
      functional theory. Both guests (RhB and KRS) contain two N,N-diethylamino groups
      on a xanthene core. The lowest-energy structure of these host-guest complexes has
      one of the N,N-diethylamino groups encapsulated within the host cavity, that
      engenders C-H...O interactions with portals, while the remaining noninteracting
      diethylamino group resides outside the cavity. The (1)H NMR chemical shifts
      derived using the gauge-independent atomic orbital method are consistent with
      those observed in experiments.

PMID- 22392433
TI  - Cooperativity effects in linear formaldehyde oligomers using density functional
      theory calculations.
AB  - This work reports hydrogen bonding interaction in linear formaldehyde oligomers
      using density functional theory method. Many-body analysis technique has been
      used to study the various interactions in these oligomers and to obtain %
      contributions from individual many-body energy terms to the binding energies of
      these oligomers. Co-operativity effects are studied using different indicators
      viz. hydrogen bond strength, inter- and intramolecular distances, dissociation
      energy, dipole co-operativity, energy per hydrogen bond, excess energy and non
      additive energy. All these indicators show strong positive hydrogen bond co
      operativity in linear formaldehyde oligomers. The dipole moment changes from 2.51
      D in monomer to 20.92 D in formaldehyde heptamer.

PMID- 22392432
TI  - Insights into the mechanisms of the selectivity filter of Escherichia coli
      aquaporin Z.
AB  - Aquaporin Z (AQPZ) is a tetrameric protein that forms water channels in the cell
      membrane of Escherichia coli. The histidine residue (residue 174) in the
      selectivity filter (SF) region plays an important role in the transport of water
      across the membrane. In this work, we perform equilibrium molecular dynamics (MD)
      simulations to illustrate the gating mechanism of the SF and the influences of
      residue 174 in two different protonation states: Hsd174 with the proton at
      Ndelta, and Hse174 with the proton at Nepsilon. We calculate the pore radii in
      the SF region versus the simulation time. We perform steered MD to compute the
      free-energy profile, i.e., the potential of mean force (PMF) of a water molecule
      through the SF region. We conduct a quantum mechanics calculation of the binding
      energy of one water molecule with the residues in the SF region. The hydrogen
      bonds formed between the side chain of Hsd174 and the side chain of residue 189
      (Arg189) play important roles in the selectivity mechanism of AQPZ. The radii of
      the pores, the hydrogen-bond analysis, and the free energies show that it is
      easier for water molecules to permeate through the SF region of AQPZ with residue
      174 in the Hse state than in the Hsd state.

PMID- 22392434
TI  - Trabectedin has promising antineoplastic activity in high-grade meningioma.
AB  - BACKGROUND: Meningiomas are common intracranial tumors arising from the meninges
      and usually are benign. However, a few meningiomas have aggressive behavior and,
      for such patients, effective treatment options are needed. Trabectedin is a
      novel, marine-derived, antineoplastic agent that has been approved and is used
      routinely as therapy for advanced soft tissue sarcoma and ovarian cancer.
      METHODS: The authors investigated the in vitro effects of trabectedin alone and
      in combination with hydroxyurea, cisplatin, and doxorubicin in primary cell
      cultures of benign (n = 9), atypical (n = 6), and anaplastic (n = 4) meningiomas
      using chemosensitivity assays (3-[4,5dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide [MTT]), Western blot analysis, cell cycle analysis,
      and immunofluorescent staining. RESULTS: Strong antimeningioma activity of
      trabectedin was observed and was characterized by distinct cell cycle arrest,
      down-regulation of multiple cyclins, deregulated expression of cell death
      regulatory genes, and massive apoptosis induction. Cytotoxic activity was
      especially intense in higher grade meningiomas with a half-maximal inhibitory
      concentration <10 nM. Combination with trabectedin synergistically enhanced the
      antimeningioma activity of hydroxyurea but also enhanced the activity of
      doxorubicin and cisplatin. On the basis of these findings, trabectedin was given
      to 1 patient who had heavily pretreated, anaplastic meningioma, and a favorable
      response was observed with radiologic disease stabilization, marked reductions in
      brain edema and requirement for corticosteroids, and improvement of clinical
      symptoms. However, treatment had to be discontinued after 5 cycles because of
      adverse drug effects. CONCLUSIONS: The current results indicated that trabectedin
      may represent a promising new therapeutic option for patients with aggressive
      meningioma and should be evaluated in prospective clinical studies.

PMID- 22392435
TI  - Rickettsia slovaca and Rickettsia raoultii in Dermacentor marginatus and
      Dermacentor reticulatus ticks from Slovak Republic.
AB  - Rickettsiae, obligate intracellular Gram-negative bacteria, responsible for mild
      to severe diseases in humans are associated with arthropod vectors. Dermacentor
      marginatus and Dermacentor reticulatus are known vectors of Rickettsia slovaca
      and Rickettsia raoultii distributed across Europe. A total of 794 D. marginatus,
      D. reticulatus and Ixodes ricinus adult ticks were collected from the vegetation,
      removed from horses, sheep, goats and dogs in Slovakia. The DNA of Rickettsia sp.
      was found in 229 ticks by PCR amplifying parts of gltA, ompA and sca4 genes. Next
      analyses of Rickettsia-positive samples by PCR-RFLP and/or sequencing showed D.
      reticulatus ticks were more infected with R. raoultii and D. marginatus were more
      infected with R. slovaca. The prevalence of R. raoultii was 8.1-8.6% and 22.3-27%
      in D. marginatus and D. reticulatus, respectively. The prevalence of R. slovaca
      was 20.6-24.3% in D. marginatus and 1.7-3.4% in D. reticulatus. Intracellular
      growth of R. raoultii isolate from D. marginatus tick was evaluated by rOmpA
      based quantitative SybrGreen PCR assay. The highest point of multiplication was
      recorded on the 7th and 8th day postinfection in Vero and L929 cells,
      respectively. R. raoultii was transmitted during feeding of R. raoultii-positive
      ticks to guinea pigs and subsequently rickettsial infection was recorded in all
      organs, the highest infection was in spleen, liver and heart. Our study describes
      the detection and isolation of tick-borne pathogens R. raoultii and R. slovaca,
      show that they are spread in Slovakia and highlight their risk for humans.

PMID- 22392436
TI  - Raoiella indica (Acari: Tenuipalpidae): an exploding mite pest in the neotropics.
AB  - Major infestations of the flat mite species Raoiella indica Hirst affecting
      bananas, palms and other ornamental plants have been reported from the Caribbean
      islands, Mexico, FL (USA), Venezuela, Colombia and Brazil. Specimens from these
      localities were examined using traditional light microscopy and low-temperature
      scanning electron microscopy techniques. While little is known about the biology
      of this mite, its recent appearance in the Americas in both commercial coconut
      and banana plantations has raised concerns about its economic impact as an
      invasive pest.

PMID- 22392438
TI  - Hemichannels: permeants and their effect on development, physiology and death.
AB  - Hemichannels, which are one half of the gap junction channels, have independent
      physiological roles. Although hemichannels consisting of connexins are more
      widely documented, hemichannels of pannexins, proteins homologous to invertebrate
      gap junction proteins also have been studied. There are at least 21 different
      connexin and three pannexin isotypes. This variety in isotypes results in tissue
      specific hemichannels, which have been implicated in varied events ranging from
      development, cell survival, to cell death. Hemichannel function varies with its
      spatio-temporal opening, thus demanding a refined degree of regulation. This
      review discusses the activity of hemichannels and the molecules released in
      different physiological states and their impact on tissue functioning.

PMID- 22392441
TI  - Upcoming special issues in the Journal of Community Genetics.

PMID- 22392440
TI  - Genetics of autoimmune thyroid disease in the Lebanese population.
AB  - This study aims to investigate the association of human leukocyte antigen (HLA)
      class II genes and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) with
      autoimmune thyroid diseases in the Lebanese population. A total of 128 patients
      with autoimmune thyroid disease (55 with Graves' disease (GD) and 73 with
      Hashimoto's thyroiditis (HT)) were typed for HLA DQA1 (0301 and 0501) and DQB1
      (0201, 0302, and 0303) and for 49A/G CTLA-4 using PCR-based sequence-specific
      priming methods. A total of 186 matched controls were typed for the same alleles
      and compared to the diseased population. Results showed no significant
      differences in HLA DQB1*0201 or DQB1*0301 allelic frequencies or CTLA-4
      polymorphisms between patients and controls. For GD, there was a weak association
      with HLA DQB1*0302 [34.6% (19 of 55) vs. 21.5% (40 of 186), P = 0.048, odds ratio
      (OR) = 1.926, confidence interval (CI) = 0.999-3.715] and HLA DQB1*0302-DQA1*0501
      haplotype [56.36% (31 of 55) vs. 40.8% (76 of 186), P = 0.042, OR = 1.870, CI =
      1.018-3.433]. For HT, the frequencies of DQB1*0302-DQA1*0501 haplotype [28.8%
      (21of 73) vs. 14.5% (27 of 186), P = 0.008, OR = 2.378, CI = 1.241-4.558] and
      DQB1*0302-DQA1*0301 haplotype [60.2% (44 of 73) vs. 38.7% (72 of 186), P = 0.002,
      OR = 2.402, CI = 1.381-4.180] were significantly higher in patients. On the other
      hand, weak association was found between HT and DQA1*0301 allele [32.9% (24 of
      73) vs. 20.9% (39 of 186), P = 0.044, OR = 1.846, CI = 1.011-3.373]. Findings
      show that DQB1*0302-DQA1*0501 and DQB1*0302-DQA1*0301 haplotypes may play a role
      in the pathogenesis of HT in the Lebanese population. For the 49A/G CTLA-4
      polymorphism, no significant difference was found between patients and controls.

PMID- 22392442
TI  - Novel crystalloid oligodendrogliopathy in hereditary spastic paraplegia.
AB  - Hereditary spastic paraplegia (HSP) comprises a group of clinically and
      genetically heterogeneous disorders associated with spastic paraparesis (pure
      HSP) with or without additional neurological symptoms (complicated HSP). Here we
      present a case of an adult-onset, apparently autosomal-dominant, complicated form
      of HSP. Onset of clinical symptoms was at the age 40 years and characterised by
      slowly progressive corticospinal tract dysfunction, dysarthria, disorientation,
      extrapyramidal symptoms, and bilateral ptosis. Cranial MRI revealed
      hyperintensities on T2-weighted sequences mostly in the posterior limb of the
      internal capsule. The proband deceased at the age of 64 years. As morphological
      substrate for the slowly progressive clinical symptoms, comprehensive
      neuropathological and ultrastructural evaluation revealed a novel
      oligodendrogliopathy with distinctive, partly ubiquitinated and p62 positive
      fibrillar inclusions evolving into crystalloid deposits, containing elements of
      the oligodendroglial cytoskeleton (alpha- and beta-tubulin, TPPP/p25). In the
      central nervous system, accumulation of crystalloid structures has been related
      to histiocytes but not to glial cells. This study has implications for the
      understanding on how the human central nervous system reacts to protracted
      dysfunction and disruption of the oligodendroglial cytoskeleton, including
      development of crystalloid structures, which have not yet been reported in
      neurodegenerative diseases including HSP.

PMID- 22392443
TI  - Medulloblastoma: a potpourri of distinct entities.

PMID- 22392444
TI  - Does tool use extend peripersonal space? A review and re-analysis.
AB  - The fascinating idea that tools become extensions of our body appears in
      artistic, literary, philosophical, and scientific works alike. In the last 15
      years, this idea has been reframed into several related hypotheses, one of which
      states that tool use extends the neural representation of the multisensory space
      immediately surrounding the hands (variously termed peripersonal space, peri-hand
      space, peri-cutaneous space, action space, or near space). This and related
      hypotheses have been tested extensively in the cognitive neurosciences, with
      evidence from molecular, neurophysiological, neuroimaging, neuropsychological,
      and behavioural fields. Here, I briefly review the evidence for and against the
      hypothesis that tool use extends a neural representation of the space surrounding
      the hand, concentrating on neurophysiological, neuropsychological, and
      behavioural evidence. I then provide a re-analysis of data from six published and
      one unpublished experiments using the crossmodal congruency task to test this
      hypothesis. While the re-analysis broadly confirms the previously reported
      finding that tool use does not literally extend peripersonal space, the overall
      effect sizes are small and statistical power is low. I conclude by questioning
      whether the crossmodal congruency task can indeed be used to test the hypothesis
      that tool use modifies peripersonal space.

PMID- 22392445
TI  - Remapping of the line motion illusion across eye movements.
AB  - Although motion processing in the brain has been classically studied in terms of
      retinotopically defined receptive fields, recent evidence suggests that motion
      perception can occur in a spatiotopic reference frame. We investigated the
      underlying mechanisms of spatiotopic motion perception by examining the role of
      saccade metrics as well as the capacity of trans-saccadic motion. To this end, we
      used the line motion illusion (LMI), in which a straight line briefly shown after
      a high contrast stimulus (inducer) is perceived as expanding away from the
      inducer position. This illusion provides an interesting test of spatiotopic
      motion because the neural correlates of this phenomenon have been found early in
      the visual cortex and the effect does not require focused attention. We measured
      the strength of LMI both with stable fixation and when participants were asked to
      perform a 10 degrees  saccade during the blank ISI between the inducer and the
      line. A strong motion illusion was found across saccades in spatiotopic
      coordinates. When the inducer was presented near in time to the saccade cue,
      saccadic latencies were longer, saccade amplitudes were shorter, and the strength
      of reported LMI was consistently reduced. We also measured the capacity of the
      trans-saccadic LMI by varying the number of inducers. In contrast to a visual
      spatial memory task, we found that the LMI was largely eliminated by saccades
      when two or more inducers were displayed. Together, these results suggest that
      motion perceived in non-retinotopic coordinates depends on an active, saccade
      dependent remapping process with a strictly limited capacity.

PMID- 22392446
TI  - The use of outpatient mental health care services of migrants vis-a-vis Dutch
      natives: equal access?
AB  - BACKGROUND: Although the use of outpatient mental health care services by
      migrants in the Netherlands has increased in recent years, whether it aligns with
      the need for care is unclear. AIMS: To investigate ethnic-related differences in
      utilization in outpatient mental health care, taking need into account, and to
      examine whether socio-economic or cultural barriers explain such differences.
      METHODS: Data for the native population was taken from the second Dutch National
      Survey of General Practice (N = 7,772). An additional random sample was drawn (N
      = 1,305) from four migrant groups (Surinamese, Dutch Antilleans, Moroccans and
      Turks) living in the Netherlands. Participants were surveyed on mental health
      care utilization, indicators of need, educational level, proficiency in Dutch and
      acculturation. RESULTS: Use of outpatient mental health care was about 5% for the
      indigenous population. Among migrants, percentages of use ranged from 6.5%
      (Moroccans) to 9.0% (Turks). Corrected for need, however, all non-Dutch groups
      had a lower chance of service utilization than the native group. Acculturation
      predicted utilization but did not explain all ethnic-related differences;
      proficiency in Dutch and health beliefs were not explanatory factors.
      CONCLUSIONS: In non-Dutch-speaking migrant groups, utilization is about half the
      level of the native Dutch, suggesting that a substantial gap exists. Our study
      found that acculturation only partially explains the differences.

PMID- 22392447
TI  - Rapid high resolution electroanatomical mapping: evaluation of a new system in a
      canine atrial linear lesion model.
AB  - BACKGROUND: A canine right atrial (RA) linear lesion model was used to produce a
      complex pattern of RA activation to evaluate a novel mapping system for rapid,
      high resolution (HR) electroanatomical mapping. METHODS AND RESULTS: The mapping
      system (Rhythmia Medical, Incorporated) uses an 8F deflectable catheter with a
      minibasket (1.8 cm diameter), containing 8 splines of 8 electrodes (total 64
      electrodes, 2.5 mm spacing). The system automatically acquires electrograms and
      location information based on electrogram stability and respiration phase. In 10
      anesthetized dogs, HR-RA map was obtained by maneuvering the minibasket catheter
      during sinus rhythm and coronary sinus pacing. A right thoracotomy was performed,
      and either 1 or 2 (to create a gap) epicardial linear lesions were created on the
      RA free wall (surgical incision or epicardial radiofrequency lesions). RA maps
      during RA pacing close to the linear lesions were obtained. A total of 73 maps
      were created, with 44 to 729 (median 237) beats and 833 to 12 412 (median 3589)
      electrograms (<=2 to <=5 mm from surface geometry), resolution 1.8 to 5.3 (median
      2.7) mm, and 2.6 to 26.3 (median 7.3) minutes mapping time. Without manual
      annotation, the system accurately created RA geometry and demonstrated RA
      activation, identifying the location of lines of block and presence or absence of
      a gap in all 10 dogs. Endocardial radiofrequency catheter ablation of a gap
      (guided by activation map) produced complete block across the gap in all 3 dogs
      tested. CONCLUSIONS: The new HR mapping system accurately and quickly identifies
      geometry and complex patterns of activation in the canine RA, with little or no
      manual annotation of activation time.

PMID- 22392449
TI  - Rhodium pyrazolate complexes as potential CVD precursors.
AB  - Reaction of 3,5-(CF(3))(2)PzLi with [Rh(MU-Cl)(eta(2)-C(2)H(4))(2)](2) or [Rh(MU
      Cl)(PMe(3))(2)](2) in Et(2)O gave the dinuclear complexes [Rh(eta(2)
      C(2)H(4))(2)(MU-3,5-(CF(3))(2)-Pz)](2) (1) and [Rh(2)(MU-Cl)(MU-3,5-(CF(3))(2)
      Pz) (PMe(3))(4)] (2) respectively (3,5-(CF(3))(2)Pz = bis-trifluoromethyl
      pyrazolate). Reaction of PMe(3) with [Rh(COD)(MU-3,5-(CF(3))(2)-Pz)](2) in
      toluene gave [Rh(3,5-(CF(3))(2)-Pz)(PMe(3))(3)] (3). Reaction of 1 and 3 in
      toluene (1 : 4) gave moderate yields of the dinuclear complex [Rh(PMe(3))(2)(MU
      3,5-(CF(3))(2)-Pz)](2) (4). Reaction of 3,5-(CF(3))(2)PzLi with [Rh(PMe(3))(4)]Cl
      in Et(2)O gave the ionic complex [Rh(PMe(3))(4)][3,5-(CF(3))(2)-Pz] (5). Two of
      the complexes, 1 and 3, were studied for use as CVD precursors. Polycrystalline
      thin films of rhodium (fcc-Rh) and metastable-amorphous films of rhodium
      phosphide (Rh(2)P) were grown from 1 and 3 respectively at 170 and 130  degrees
      C, 0.3 mmHg in a hot wall reactor using Ar as the carrier gas (5 cc min(-1)).
      Thin films of amorphous rhodium and rhodium phosphide (Rh(2)P) were grown from 1
      and 3 at 170 and 130  degrees C respectively at 0.3 mmHg in a hot wall reactor
      using H(2) as the carrier gas (7 cc min(-1)).

PMID- 22392448
TI  - The association of bipolar spectrum disorders and borderline personality
      disorder.
AB  - Bipolar disorder (BD) and borderline personality disorder (BPD) are two different
      entities sharing a variety of common features in a number of fields and, thus,
      presenting difficulties in their differential diagnosis. The aim of the review is
      to identify similarities and differences between BD and BPD concerning the
      symptomatology, causes, course and treatment of the two disorders. A systematic
      electronic search of Pubmed (Medline) was conducted in order to identify all
      relevant scientific articles published between 1990 and 2010. The main common
      clinical features of BD and BPD are affective instability and impulsivity, which,
      however, present with quality differences in each disorder. In the field of
      neuroanatomy, BD and BPD demonstrate similarities such as alterations in the
      limbic system, as well as specific differences, such as the increase in size of
      the amygdala in BD and the decrease in BPD. Both disorders appear to have a
      significant percentage of heritability, but environmental factors seem to hold an
      important role in BPD, in particular. Both BD and BPD are affected by alterations
      in the dopaminergic and serotonergic system. Fuctionability and prognosis are
      slightly worse for BPD. Concerning medication treatment, antidepressants are
      considered effective in BPD, whereas mood stabilizers are the main treatment of
      choice in BD. The effectiveness of a variety of psychotherapeutic methods is
      still under research for both disorders. Despite the similarities and differences
      already being traced in clinical and biological fields, the relationship of the
      two disorders has not yet been thoroughly defined.

PMID- 22392450
TI  - Distinct roles for complement in glomerulonephritis and atherosclerosis revealed
      in mice with a combination of lupus and hyperlipidemia.
AB  - OBJECTIVE: Although the accelerating effect of systemic lupus erythematosus (SLE)
      on atherosclerosis is well established, the underlying mechanisms are unknown.
      The aim of this study was to explore the hypothesis that lupus autoimmunity
      modulates the effect of hypercholesterolemia in driving arterial pathologic
      development. METHODS: Low-density lipoprotein receptor-deficient (Ldlr(-/-) )
      mice were crossed with B6.129-Sle16 (Sle16)-congenic autoimmune mice to obtain
      Sle16. Ldlr(-/-) mice, which were compared with Ldlr(-/-) and Sle16 control mice.
      All mice were fed either a low-fat or high-fat diet. Groups of mice were
      compared, by strain and by diet group, for features of accelerated
      atherosclerosis and autoimmunity. RESULTS: Presence of the Sle16 locus
      significantly increased the extent of atherosclerosis in Ldlr(-/-) mice.
      Circulating C3 levels were significantly reduced in Sle16.Ldlr(-/-) mice compared
      to Ldlr(-/-) control mice and this was paralleled by a marked reduction in
      arterial lesion C3 deposition despite similar levels of IgG deposition between
      the groups. Increased numbers of apoptotic cells in plaques were observed in the
      high-fat-fed Sle16.Ldlr(-/-) mice, consistent with the observed defective
      clearance of cellular debris. After receiving the high-fat diet, Sle16.Ldlr(-/-)
      mice developed glomerulonephritis and displayed enhanced glomerular C3
      deposition. CONCLUSION: These results indicate that accelerated atherosclerosis
      and renal inflammation in SLE are closely linked via immune complex formation and
      systemic complement depletion. However, whereas hyperlipidemia will enhance renal
      immune complex-mediated complement activation and the development of nephritis,
      accelerated atherosclerosis is, instead, related to complement depletion and a
      reduction in the uptake of apoptotic/necrotic debris. These results suggest that
      aggressive treatment of hyperlipidemia in patients with SLE may reduce the
      occurrence of lupus nephritis, as well as diminish the risk of accelerated
      atherosclerosis.

PMID- 22392451
TI  - Posterior condylar cartilage may distort rotational alignment of the femoral
      component based on posterior condylar axis in total knee arthroplasty.
AB  - PURPOSE: Among several anatomical references, the posterior condylar axis is the
      most apparent landmark to decide the femoral rotation for total knee
      arthroplasty. External rotation based on the posterior condylar axis requires
      condylar twist angle in order to set the femoral component parallel to trans
      epicondylar axis although the angle is not constant. The angle during surgery
      differs from the pre-operative measurement on epicondylar view, because X-rays do
      not show the posterior condylar residual cartilage thickness. The thickness
      should be measured for the accurate femoral rotation. METHODS: We investigated
      the two twist angles on preoperative X-ray and during surgery, and the impact of
      residual cartilage on the setting of rotational angle of the femoral component in
      184 knees in 112 patients with varus osteoarthritis (mean femorotibial angle: 185
      +/- 6.9 from 169 to 205 degrees ). RESULTS: The twist angle during surgery was
      5.2 +/- 1.3 degrees  (1.5-8.5 degrees ) and the angle on X-ray was 6.5 +/- 2.3
      degrees  (0.6-13.5 degrees ). The rotational angle influenced by the residual
      cartilage was calculated to be 1.7 +/- 1.3 degrees  (0.0-4.6 degrees ). The
      discrepancy in the two twist angles was close to the rotational angle. There
      were, however, wide variations in all angles. CONCLUSION: The results suggested
      the importance of considering the influence of the residual cartilage and the
      individual variation in determining the femoral component setting. Multiple
      reference frames for femoral component rotation or combination with gap technique
      may help to minimize malalignment which may lead to poor clinical outcome.

PMID- 22392452
TI  - Effects of targeting higher vancomycin trough levels on clinical outcomes and
      costs in a matched patient cohort.
AB  - STUDY OBJECTIVE: To compare clinical outcomes and costs in patients treated with
      the new vancomycin guidelines recommending goal serum trough concentrations of 15
      20 mg/L versus patients treated with vancomycin doses targeting trough
      concentrations 5-20 mg/L prior to the new guidelines. DESIGN: Retrospective quasi
      experimental study. SETTING: Urban level I trauma center. PATIENTS: A total of
      200 patients treated with vancomycin for at least 72 hours for confirmed,
      complicated methicillin-resistant Staphylococcus aureus (MRSA) bacteremia during
      one of two study phases relative to the implementation of the vancomycin dosing
      guidelines targeting serum trough concentrations of 15-20 mg/L: 2005-2007
      (preperiod phase) and 2008-2010 (postperiod phase). One hundred patients in each
      phase were matched in a 1:1 ratio according to diagnosis, any concomitant
      nephrotoxic agents (e.g., aminoglycosides, colistin, acyclovir), and age +/- 5
      years. MEASUREMENTS AND MAIN RESULTS: Patients in the preperiod had significantly
      lower success rates with vancomycin than those in the postperiod (45% vs 60%,
      p=0.034). Median length of stay (LOS) was not significantly higher in patients in
      the preperiod versus postperiod (15 days vs 13.5 days; p=0.28), and patients in
      the preperiod received a longer median duration of vancomycin versus those in the
      postperiod (13 days vs 8.5 days; p<0.001). No statistically significant
      difference was noted in total hospital costs for patients treated with vancomycin
      during the preperiod versus the postperiod ($32,754 vs $27,709, p=0.147).
      However, total drug and monitoring costs of vancomycin were significantly higher
      for patients in the postperiod. Initial vancomycin trough levels were
      significantly lower in patients in the preperiod versus postperiod (12.3 mg/L vs
      15.8 mg/L, p=0.02). Patients in the preperiod had lower rates of nephrotoxicity
      than those in the postperiod, although this difference was not statistically
      significant (15% vs 18%; p=0.85). Median (interquartile range) LOS was
      significantly longer in patients who developed nephrotoxicity compared with
      patients who did not develop nephrotoxicity (17 days [11.5-36.5 days] vs 14 days
      [9-24 days], p=0.017). Costs associated with measurement of serum creatinine
      concentrations and vancomycin trough levels as well as labor were significantly
      higher in patients who developed nephrotoxicity. CONCLUSION: Higher vancomycin
      trough concentrations improved outcomes in patients with complicated MRSA
      bacteremia. In addition, more aggressive dosing was shown to significantly
      decrease overall duration of vancomycin therapy, which may affect total hospital
      LOS and cost. Patients who experienced nephrotoxicity had a significantly longer
      hospital LOS. Additional studies evaluating optimal therapy for MRSA bacteremia
      in a larger cohort of matched patients are warranted.

PMID- 22392453
TI  - Relationship between changes in inhaled corticosteroid use and markers of
      uncontrolled asthma during pregnancy.
AB  - STUDY OBJECTIVE: To describe changes in inhaled corticosteroid use during
      pregnancy and markers of uncontrolled asthma, and to evaluate the association
      between them. DESIGN: Population-based, cross-sectional study. DATA SOURCE: Three
      administrative claims databases in Quebec, Canada. PATIENTS: A cohort of 4434
      asthmatic women (4920 pregnancies) who delivered their infants between 1990 and
      2002 and who used inhaled corticosteroids before their pregnancy. MEASUREMENTS
      AND MAIN RESULTS: The average daily doses of inhaled corticosteroids during
      pregnancy and during the 9 months before conception were compared; the change in
      use was categorized as discontinuation (reduction of >=75%), reduction (26-75%
      reduction), no change (+/-25% change), or increase (increase of >=25%). The
      markers of uncontrolled asthma included at least one asthma exacerbation and the
      use of three or more doses/week of a short-acting beta(2) -agonist during
      pregnancy. Generalized estimating equation models were used for statistical
      analyses. In nearly 50% of the pregnancies (2388 [48.5%] of 4920), the women
      either stopped or reduced their doses of corticosteroid during pregnancy, and
      these doses were already quite low before pregnancy. The proportion of women who
      had an asthma exacerbation during pregnancy was 8.2% among women who discontinued
      corticosteroids and greater than 20% in all of the other groups. All of the
      groups used frequent doses of short-acting beta(2) -agonists. Discontinuing
      inhaled corticosteroid use during pregnancy was associated with a lower risk of
      exacerbations (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.33-0.54),
      whereas increasing inhaled corticosteroid use was associated with a higher risk
      (OR 1.42, 95% CI 1.17-1.72), compared with no change in use. CONCLUSION: Because
      of residual confounding by asthma severity, our study was not able to show that
      women who stopped inhaled corticosteroids during pregnancy were at increased risk
      of having an asthma exacerbation. However, women who stopped corticosteroids
      tended to have a milder form of asthma, which is reassuring and suggests that
      women can recognize, to a certain extent, the need to continue taking their
      controller agents if necessary.

PMID- 22392454
TI  - Measuring and reporting of the treatment effect of hormonal emergency
      contraceptives.
AB  - STUDY OBJECTIVES: To derive summary estimates of observed pregnancy rates in
      women who used the Yuzpe or levonorgestrel emergency contraceptive regimen and
      identify the various ways in which data related to regimen effectiveness were
      reported, to discuss the limitations of the effectiveness estimates as they are
      currently reported, and to propose alternative reporting methods that are less
      susceptible to misinterpretation. DESIGN: Analysis of pooled data from 34
      experimental or observational studies that had an explicit method of follow-up to
      systematically evaluate pregnancy outcome after a single course of emergency
      contraception treatment within a given menstrual cycle. PATIENTS: Women who took
      either the Yuzpe or levonorgestrel emergency contraceptive regimen to prevent
      pregnancy. MEASUREMENTS AND MAIN RESULTS: We searched the MEDLINE and EMBASE
      databases for clinical studies that systematically evaluated pregnancy outcomes
      of women who used the Yuzpe or levonorgestrel regimen for emergency
      contraception. The effectiveness of these regimens is typically reported in
      relative terms as the reduction of pregnancy risk from a theoretical baseline
      risk. We reported the effectiveness using absolute risk reductions and numbers
      needed to treat. We pooled relevant data by using the beta-binomial method to
      derive observed pregnancy rates. The pooled observed pregnancy rates for studies
      of the Yuzpe and levonorgestrel regimens were 2.0% (95% confidence interval [CI]
      1.5-2.5%) and 1.7% (95% CI 1.2-2.2%), respectively. Against expected pregnancy
      rates of 4-8%, relative emergency contraceptive effectiveness ranges were 50.0
      75.0% and 57.5-78.8% for the Yuzpe and levonorgestrel regimens, respectively.
      Absolute risk reductions were 2.0-6.0% and 2.3-6.3%, respectively. This means
      that 17-50 women would need to have received the Yuzpe regimen and 16-43 women
      the levonorgestrel regimen to prevent one pregnancy. CONCLUSION: Emergency
      contraception effectiveness data are susceptible to misinterpretation when data
      are reported in relative terms without the expected pregnancy rate (i.e., the
      baseline risk). We recommend that the effect of emergency contraceptives be
      expressed in absolute terms and accompanied by the expected pregnancy rate used
      in its estimation.

PMID- 22392455
TI  - A systematic review of the evidence for pharmacist care of patients with
      dyslipidemia.
AB  - STUDY OBJECTIVE: To evaluate the effect of pharmacist care on patients with
      dyslipidemia. DESIGN: Systematic review of 21 randomized controlled trials.
      PATIENTS: A total of 5416 patients who received enhanced pharmacist care or
      standard care as part of a research study. MEASUREMENTS AND MAIN RESULTS:
      Nineteen databases and four trial registries were systematically searched from
      inception through February 21, 2010, with an update in September 2011. In
      addition, Web sites of relevant professional associations, scientific meetings,
      and research groups were reviewed, and manual searches of select journals were
      performed. A total of 8771 articles were identified, and 21 studies included.
      Data from the studies were analyzed using a random-effects model. The primary
      outcome measure assessed was the difference between the groups (pharmacist
      intervention vs standard care) in low-density lipoprotein cholesterol (LDL) level
      at the end of follow-up. Secondary outcome measures included the difference
      between the groups at the end of follow-up in total cholesterol, high-density
      lipoprotein cholesterol, and triglyceride levels; and the proportion of patients
      who achieved target lipid parameters, underwent lipid panel measurements, adhered
      to therapy, and/or were instructed to change their lipid-lowering therapy. At the
      end of follow-up, the mean LDL level was 10.7 mg/dl lower in the enhanced
      pharmacy care groups compared with the standard care groups (95% confidence
      interval [CI] -16.9 to -4.6 mg/dl), with moderate heterogeneity. The mean total
      cholesterol level was significantly lower in the enhanced pharmacy care groups
      compared with the standard care groups; however, these results were highly
      heterogeneous. Patients who received enhanced pharmacist care were also more
      likely than those receiving standard care to achieve target lipid parameters
      (odds ratio [OR] 2.46, 95% CI 1.43-4.25) and to have a lipid panel ordered or
      recommended by a pharmacist during the study (OR 2.05, 95% CI 1.30-3.24).
      Patients in the pharmacist intervention groups were almost twice as likely as
      patients in the standard care groups to have a change in lipid-lowering therapy
      (OR 1.82, 95% CI 1.09-3.06). Adherence data could not be analyzed. CONCLUSION:
      This systematic review showed that enhanced pharmacist care improves lipid
      parameters, notably LDL levels, in patients with dyslipidemia. These results
      point to the benefit that pharmacist care can provide across the spectrum of
      dyslipidemia management, from screening patients to treating them to assisting
      them in the attainment of clinical targets.

PMID- 22392456
TI  - Distressing adverse events after antidepressant switch in the Sequenced Treatment
      Alternatives to Relieve Depression (STAR*D) trial: influence of adverse events
      during initial treatment with citalopram on development of subsequent adverse
      events with an alternative antidepressant.
AB  - STUDY OBJECTIVE: To determine whether distressing adverse events (DAEs)
      experienced during initial antidepressant treatment are associated with
      subsequent DAEs after switching to a second antidepressant. DESIGN: Secondary
      analysis of data from the Sequenced Treatment Alternatives to Relieve Depression
      (STAR*D) trial. SETTING: Primary care and psychiatric care facilities. PATIENTS:
      A total of 727 outpatients aged 18-75 years with nonpsychotic major depressive
      disorder who failed first-step therapy with citalopram and were switched to
      second-step monotherapy with an alternative antidepressant. MEASUREMENTS AND MAIN
      RESULTS: In the STAR*D trial, patient-reported DAEs were entered into the Patient
      Rated Inventory of Side Effects (PRISE). In this secondary analysis, data from
      PRISE were used to determine the incidence of DAEs during first-step treatment
      with citalopram and second-step treatment with sustained-release bupropion,
      sertraline, or extended-release venlafaxine. Regression models were used to
      compare the risk of adverse events during second-step treatment between those who
      reported similar adverse events during first-step treatment and those who did
      not, while controlling for potential confounders. Of the 727 patients analyzed,
      DAEs were reported by 514 patients (70.7%) during first-step treatment and 626
      (86.1%) during second-step treatment; no significant differences were observed
      among the three second-step treatment groups. Overall, patients reporting DAEs
      during first-step treatment were more likely to report DAEs during second-step
      treatment (risk ratio [RR] 1.11, 95% confidence interval [CI] 1.03-1.20). After
      controlling for confounders, patients were significantly more likely to report
      DAEs specific to a body function or organ system, such as those involving the
      genitourinary system (RR 3.39, 95% CI 2.41-4.78) or sexual functioning (RR 2.75,
      95% CI 2.29-3.29), if the patients had reported similar events during initial
      treatment. CONCLUSION: Patients who experienced DAEs with initial antidepressant
      treatment were likely to report similar adverse events after switching to an
      alternative antidepressant, even when subsequent treatment is from a different
      class of antidepressants.

PMID- 22392457
TI  - Emerging antiplatelet therapy for coronary artery disease and acute coronary
      syndrome.
AB  - Antiplatelet therapy is used widely with proven benefit for the prevention of
      further ischemic cardiac complications in patients with known coronary artery
      disease (CAD) and a history of acute coronary syndrome (ACS). The limitations of
      conventional antiplatelet therapy with aspirin, clopidogrel, or prasugrel, as
      well as the fact that rates of recurrent ischemic events still remain high with
      use of these agents, underscore the need to investigate alternate agents that may
      further reduce event rates while limiting bleeding risk. The selection of
      antiplatelet therapy is further influenced by the following: ticagrelor was
      approved in July 2011 by the United States Food and Drug Administration (FDA),
      and clopidogrel is slated to become available as a generic productin 2012. We
      provide an overview of emerging agents for the treatment of CAD and ACS,
      including the reversible P2Y(12) antagonists ticagrelor, cangrelor, and
      elinogrel, and a new class of oral protease-activated receptor-1 (PAR-1)
      inhibitors, vorapaxar and atopaxar.The recently approved P2Y(12) antagonists
      prasugrel and ticagrelor demonstrate enhanced ability to prevent adverse cardiac
      outcomes. However, this comes at a cost of a potential increased risk of
      bleeding. New adverse effects have also emerged, including dyspnea for all of the
      reversible P2Y(12) antagonists (ticagrelor, cangrelor, and elinogrel) and
      ventricular pauses for ticagrelor. In addition, the newer P2Y(12) antagonists
      have a faster onset and offset. Two of these agents, cangrelor and elinogrel, are
      available as intravenous formulations, which may provide additional benefits in
      patients who undergo coronary artery bypass graft (CABG) surgery. Trials with the
      PAR-1 inhibitors have also shown trends toward reductions in cardiac events, but
      not without the possibility of increased bleeding. More than ever, as the arsenal
      of antiplatelet therapy expands, health care providers need to understand the
      pharmacologic and pharmacodynamic differences between conventional and emerging
      antiplatelet therapies for patients with ACS and CAD. Health care providers must
      also carefully assess patient-specific factors such as risk of thrombosis,
      concomitant disease states, age, drug adherence, and aspirin dose, and plan for
      those patients who will be undergoing CABG when selecting antiplatelet therapy in
      order to optimally balance bleeding and thrombosis risk.

PMID- 22392458
TI  - Denosumab for the prevention of skeletal-related events in patients with bone
      metastasis from solid tumor.
AB  - Most patients with advanced malignancy develop bone metastases during the course
      of their disease. For the remainder of the patient's life, these bone metastases
      lead to skeletal-related events such as pathologic fractures and spinal cord
      compression, as well as bone pain or lesions requiring palliative radiation
      therapy or surgery to prevent or treat fractures. Skeletal-related events result
      in increased morbidity, mortality and health care costs. For the past decade,
      intravenous bisphosphonates (zoledronic acid, pamidronate) have been recognized
      as the primary pharmacologic options in the prevention or treatment of skeletal
      related events in patients with bone metastasis. Recently, the United States Food
      and Drug Administration approved denosumab, a fully human monoclonal antibody,
      for the prevention of skeletal-related events in patients with bone metastases
      from solid tumors. Three prominent clinical trials were conducted to establish
      the efficacy of denosumab. In two of three trials, denosumab was found to delay
      the time to first skeletal-related event significantly more than zoledronic acid
      in patients with breast or castration-resistant prostate cancer with bone
      metastasis. The third trial found denosumab to be noninferior to zoledronic acid
      in patients with metastases from solid tumors, excluding breast and prostate
      solid tumors. Overall survival and progression-free survival were similar between
      zoledronic acid and denosumab. Thus, evidence is insufficient to prove a greater
      efficacy of one agent over the other. According to the American Society of
      Clinical Oncology and the National Comprehensive Cancer Network, patients with
      bone metastasis should have zoledronic acid, pamidronate, or denosumab (with
      calcium and vitamin D supplementation) added to their chemotherapy regimen if
      they have an expected survival of 3 months or longer and have adequate renal
      function.

PMID- 22392459
TI  - The CHADS2versus the new CHA2DS2-VASc scoring systems for guiding antithrombotic
      treatment of patients with atrial fibrillation: review of the literature and
      recommendations for use.
AB  - The association of atrial fibrillation and resultant thromboembolic stroke is
      readily recognized in the published literature. However, the identification and
      weight of other risk factors that increase stroke risk are varied. To predict
      which patients are at greatest risk for thromboembolic stroke, numerous risk
      stratification schemas have been developed to guide thromboprophylactic treatment
      decisions. The well-known CHADS(2) scoring system incorporates risk factors such
      as congestive heart failure, hypertension, age 75 years or older, diabetes
      mellitus, and previous stroke or transient ischemic attack. Recently, a novel
      risk stratification model, CHA2DS2 -VASc, has entered the literature and
      international guidelines, prompting further review of newly added risk factors
      age 65-74 years, presence of vascular disease, and female sex-and the increased
      allotment of 2 points (vs 1 point in CHADS2) for age 75 years or older. The
      rationale for CHA2DS2 -VASc, as put forth by its authors, is that other risk
      assessment models omit important risk factors, have low predictive ability, and
      categorize too many patients as intermediate risk, leaving the choice of
      anticoagulant or antiplatelet therapy to the discretion of the clinician.
      Although CHA2DS2 -VASc readily identifies those patients truly at low risk, it
      classifies more patients as high risk who would then receive anticoagulation
      therapy. Therefore, implementation of this risk schema warrants further
      evaluation, especially when weighing the risk for bleeding and the risk for
      stroke. This critical review provides practitioners with an understanding of the
      literature that prompted the inclusion of these new risk factors and increased
      point allocations, compares and contrasts the risk schemas, and reviews national
      and international guidelines, thereby equipping the health care provider with the
      knowledge to aid clinical decision-making.

PMID- 22392460
TI  - Successful management of anticoagulation therapy during international travel.
AB  - Warfarin is considered a high-risk drug because of its narrow therapeutic window,
      variability in dose response, and multitude of drug and food interactions.
      Although travel advice is available for patients who are taking warfarin, it is
      geared toward patients who are traveling to developed countries and tends to be
      lacking in detail. We describe a 53-year-old woman with two mechanical heart
      valves and chronic atrial fibrillation who was taking warfarin for
      thromboembolism prophylaxis and had plans to travel to Vietnam for 10 weeks.
      Three days before her departure, she was prescribed amiodarone for long-term use.
      As a result of the extended duration of her travel and the complexities of
      warfarin use, the pharmacists who managed the patient's anticoagulation reviewed
      several aspects of a comprehensive management approach with the patient for a
      safe international trip. They assessed the patient's thromboembolic and
      hemorrhagic risks, and determined which other drugs (e.g., enoxaparin,
      phytonadione), dosages, and adequate supplies would be required along with
      warfarin, as well as how to safely transport these drugs during travel. In
      addition, the logistics of effectively monitoring international normalized ratio
      (INR) levels were evaluated, and methods of managing multiple potential scenarios
      were carefully planned out. Contact with the patient was made through pharmacist
      directed telephone visits throughout the travel period. A total of 12 telephone
      visits were conducted with the patient during the 10 weeks of travel. Her INR was
      supratherapeutic on three occasions and was subtherapeutic once; however, neither
      enoxaparin nor phytonadione were needed during the travel period, and the patient
      returned safely to the United States. Effective and safe use of high-risk drugs
      for patients leaving the United States requires extensive pretravel planning, and
      pharmacists can play a central role in optimizing therapeutic outcomes for these
      patients during international travel.

PMID- 22392461
TI  - Probable interaction between Lycium barbarum (goji) and warfarin.
AB  - Lycium barbarum (also called goji berry), a Chinese herb used as a supplement for
      health benefits, is traditionally consumed by the Chinese in the form of a tea.
      Goji juice, a widely available beverage in the United States, also contains this
      herb. We describe a 71-year-old Ecuadorean-American woman who was taking warfarin
      and was hospitalized for a markedly elevated, indeterminate international
      normalized ratio (INR) (prothrombin time > 120 sec) after consumption of goji
      juice. She had undergone knee surgery approximately 3 months earlier at which
      time warfarin therapy was started. She reported no changes in dietary habits or
      lifestyle other than drinking goji juice for 4 days before hospitalization. On
      presentation to the emergency department, she described symptoms of epistaxis,
      bruising, and rectal bleeding. After discontinuation of the goji juice and
      warfarin, the patient was treated with phytonadione, and her INR decreased to 2.6
      over 2 days. Application of the Naranjo adverse drug reaction probability scale
      indicated a probable relationship (score of 6) between the patient's elevated INR
      with associated bleeding and her concomitant use of L. barbarum and warfarin. Two
      other published reports have described similar interactions between warfarin and
      a tea containing L. barbarum. Patients should be educated about avoiding popular
      herbal drinks, such as goji juice, that contain L. barbarum while they are taking
      warfarin. In addition, clinicians should question patients about their use of
      herbal therapies and document such use in their medical records before
      prescribing drugs such as warfarin.

PMID- 22392463
TI  - [Physical activity, exercise and fitness in the field of public health].

PMID- 22392462
TI  - Curcumin ameliorates hydrogen peroxide-induced epithelial barrier disruption by
      upregulating heme oxygenase-1 expression in human intestinal epithelial cells.
AB  - BACKGROUND: Disruption of epithelial tight junctions (TJ) followed by loss of
      barrier function is of crucial importance in the pathogenesis of a variety of
      gastrointestinal disorders. Heme oxygenase-1 (HO-1), which can be induced by
      curcumin (Cur), provides protection against various forms of oxidative stress.
      AIMS: The protective effect of Cur on oxidative stress-induced intestinal barrier
      disruption in human intestinal epithelial cells was elucidated in this study.
      METHODS: H(2)O(2)-induced Caco-2 enterocytic monolayers were incubated in the
      presence or absence of Cur and/or zinc protoporphyrin (ZnPP). The trans
      epithelial electrical resistance (TEER) and the flux of sodium fluorescein in the
      filter-grown Caco-2 cell monolayers were measured. The expression and
      localization of the TJ protein occludin and zonula occluden-1 (ZO-1) were
      evaluated by western blot and immunofluorescence microscopy. The mRNA and protein
      levels of HO-1 were analyzed by real-time PCR and western blot. RESULTS: Cur
      attenuated H(2)O(2)-induced disruption of paracellular permeability (TEER 52.02
      +/- 10.15% vs 22.71 +/- 3.11%; sodium fluorescein flux 12.41 +/- 2.19% vs 32.00
      +/- 4.97%, P < 0.05) and induced HO-1 mRNA (6.64 +/- 0.48 vs 3.22 +/- 0.28, P <
      0.05) and protein (291.00 +/- 9.17% vs 99.00 +/- 10.00%, P < 0.05) expression in
      Caco-2 cells. After administration of H(2)O(2), occludin and ZO-1 proteins were
      restored by Cur (occludin 175.67 +/- 29.50% vs 53.67 +/- 24.19%, P < 0.05; ZO-1
      139.67 +/- 33.71% vs 36.00 +/- 15.88%, P < 0.05) and this effect was blocked by
      HO-1 inhibitor, ZnPP (occludin 54.67 +/- 10.02% vs 168.33 +/- 36.47%, P < 0.05;
      ZO-1 50.00 +/- 15.13% vs 117.67 +/- 38.81%, P < 0.05). CONCLUSION: Cur protects
      human intestinal epithelial cells against H(2)O(2)-induced disruption of TJ and
      barrier dysfunction via the HO-1 pathway.

PMID- 22392464
TI  - [Prevalence, degree of control and treatment of hypertension in the adult
      population of Madrid, Spain].
AB  - BACKGROUND: Hypertension (HT) is a major modifiable cardiovascular risk factors.
      The objective of this study is to estimate the adult population of the Community
      of Madrid (30-74 years) prevalence of hypertension, knowledge, degree of control
      and drug treatment. METHODS: We studied a random sample population in 2007 among
      residents of Madrid Community of between 30 and 74 years, obtained by cluster
      sampling. An epidemiological questionnaire was applied through telephone
      interview. Physical examination was conducted by a team of trained nurses in the
      health center. To assess control of hypertension by number of active ingredients
      odds were calculated through logistic regression models. RESULTS: The final
      sample included 1,085 men and 1,183 women with a mean age of 48.3 years. The
      prevalence of hypertension was 29.3% (35.1% men and 23.9% in women (p<0.01). Of
      the 665 hypertensives identified 68.6% knew their condition (62.4 76.65% in males
      and females, p<0.05), of which 54% were in drug treatment (45.4% in men and 64.5%
      in women, p<0.05). Of the 265 treated hypertensive patients, blood pressure was
      controlled in 33% of males and 49% of women, p<0.05. Patients treated with two or
      more active improves your control (aOR: 1, 89). CONCLUSIONS: Our data on
      prevalence, treatment and control are at the lower-intermediate between those
      reported in previous studies on Spanish and European populations. However, the HA
      is a public health problem in the CM. Many hypertensive patients are not
      detected. Of those detected, only 1 in 3 of men and 1 in 2 women are well
      controlled.

PMID- 22392465
TI  - [Validity of a questionnaire for the assessment of work-related musculoskeletal
      symptoms and physical demands].
AB  - BACKGROUND: Participatory ergonomics interventions are frequently based on the
      use of self-answered questionnaires intended to gathering information on work
      related musculoskeletal symptoms and physical demands reported by workers. The
      aim of this study is to assess the validity of a questionnaire designed to be
      applied in these programs. METHODS: Thirty five volunteer workers from ten
      different companies located in Valencia and Alicante (Spain) agreed to
      participate. Field work was developed in 2009. Three complementary approaches
      were applied: reproducibility in two administrations of the questionnaire;
      comparing data in the questionnaire with data from direct observation of
      workplaces; and comparing data in the questionnaire with data from routine
      reports of health surveillance and risk assessment in participating companies.
      RESULTS: Agreement indices (weighted kappa, wK) in reproducibility analyses for
      musculoskeletal symptoms in the different parts of the body (thighs being the
      only exception) were between 0.32 (95%CI 0.05-0.59) and 0.70 (95%CI 0.41-0.99).
      In general, the same analyses for exposure to the different ergonomic risks
      yielded lower agreement indices; e.g., wK for neck positions between 0.36
      (backwards, 95%CI 0.11-0.61) and 0.55 (forwards, 95%CI 0.30-0.80). In the
      analyses comparing with data from workplace observation, agreement indices were
      lower. Most items in the questionnaire show acceptable levels of agreement in
      reproducibility analyses, but lower indices when comparing with observation.
      CONCLUSIONS: Most of musculoskeletal symptoms and physical demands self-reported
      by the workers in the questionnaire were not included in the companies' routine
      health surveillance and risk assessment reports. The questionnaire is a more
      sensitive tool than routine health surveillance and risk assessments practices in
      order to identify perceived problems by workers.

PMID- 22392466
TI  - [Influence of socio-demographic correlates on the adherence to physical activity
      recommendations in adults aged from 15-to 74 years].
AB  - BACKGROUND: To know the adherence to physical activity recommendations of the
      population is of clinical and social interest. The aim of this study was to
      estimate the proportion of Spanish adults adhering to the physical activity
      recommendations, and to examine the influences of socio-demographic correlates.
      METHODS: In the present cross-sectional study we conducted a telephone survey of
      1,500 Spanish adults (15-74 years old) from Madrid (Spain). Physical activity
      (work place, transport and leisure time) was assessed with the version 2 of the
      Global Physical Activity Questionnaire (GPAQv2). Participants were categorized in
      three physical activity levels (low, moderate and high). The socio-demographic
      correlates included: gender, age, educational level, employment status, marital
      status, smoking status, and self-perceived health. The association between socio
      demographic factors and physical activity was examined with multinomial logistic
      regression analysis. RESULTS: A total of 82% of men and 78% of women (total 80%)
      had moderate to high levels of physical activity, yet, when considering the
      leisure time physical activity, only 40,1% of mean and 22,6% of women (total
      31.1%) reach the recommendations. Participants with university degree (OR: 2.05;
      95%IC: 1.48-2.86), those who were smokers (OR: 1.41; 95%IC: 1.04-1.90), and those
      who perceived their health as bad (OR: 3.58; 95%IC: 2.39-5.38) were more likely
      to not to reach the recommendations. In contrast, those participants aged 35-44
      years (OR: 0.61; 95%IC: 0.39-0.95) and 45-54 years (OR: 0.52; 95%IC: 0.32-0.83)
      were less likely not to reach the recommendations. CONCLUSIONS: The 20% of adults
      from Madrid did not reach the physical activity recommendations, and when
      considering only leisure time physical activity, only 69% reached the
      recommendations. The findings suggest that the educational level, smoking status,
      and the self-perceived health seem to be key determinants. There is a large
      diversity in the physical activity levels in the population subgroup; therefore,
      there is a need of developing social-ecological approaches to physical activity
      promotion.

PMID- 22392467
TI  - [Psychometric validation of the Spanish version of the scale properties Self
      Report Habit Index (SRHI) measuring physical exercise habits].
AB  - BACKGROUND: The measurement of physical activity habits is especially important
      in the evaluation of the consequences of chronic diseases. The study tries was to
      validate to the context Spanish the scale Self-Report Habit Index (SRHI) of 12
      items for to measure the habit strength. METHODS: The psychometric properties of
      SRHI were analyzed realizing a analysis statistical of the items, an factorial
      analysis and an estimation of the reliability coefficient via Cronbach alpha. A
      sample of 222 university students of first year was used. The majority of they
      has practiced some type of sport during his school stage. To assess the adequacy
      of sampling and possible sphericity of data obtained, both Kaiser-Meyer-Olkin
      (KMO) tests were performed (which resulted in 0.953) and Bartlett (which resulted
      in p=.000). RESULTS: The Cronbach alpha coefficient is 0.96. The results of a
      factor mining analysis (unrotated, orthogonal) point to a grouping of the 12
      items into a single factor with eigenvalue of 8.342 and a percentage of total
      variance of 69.52%. CONCLUSIONS: Results show that the scale is valid and
      reliable to measure physical activity habits A clear similarity of the
      psychometric properties of the Spanish version of the original version SRHI is
      shown.

PMID- 22392468
TI  - [Inactivity, obesity and mental health in the Spanish population from 4 to 15
      years of age].
AB  - BACKGROUND: An active lifestyle and a good weight status are two major health
      determinants from a public health perspective. AIM: To evaluate the degree of
      association between physical activity, weight status and the emotional and mental
      health of Spanish schoolchildren. METHOD: Mental health status was assessed
      through the Strengths and Difficulties Questionnaire (SDQ), also leisure time
      physical activity and body mass index (BMI) in a total of 6 803 children from 4
      to 15 years participating in the Spanish National Health Survey 2006. The degree
      of association between. these variables was estimated by a multinomial logistic
      regression analysis. RESULTS: Among sedentary schoolchildren are more common
      mental health problems (OR 2.10), emotional problems (OR 1.84), conduct problems
      (OR 1.53), problems with peers (OR 2.35) and social relationship difficulties (OR
      1.36). Obesity is associated with poor general mental health (OR 1.58), and obese
      schoolchildren show more often emotional problems (OR 1.52) and problems with
      peers (OR 2.43). CONCLUSIONS: In the Spanish schoolchildren, a healthy BMI is
      associated with increased mental well-being, although an active lifestyle is the
      best indicator of a good mental health status.

PMID- 22392469
TI  - [Tonsillopharyngitis outbreak caused by foodborne group A beta-hemolytic
      Streptococcus].
AB  - BACKGROUND: Although infrequent, some authors have reported outbreaks of
      foodborne tonsillopharyngitis. On May 11, 2010 a series of cases of
      tonsillopharyngitis among those attending a fellowship meeting on 8 March was
      notified to the Epidemiological Surveillance Network in Andalusia (SVEA). The aim
      of this study is to epidemiologically characterise the outbreak. METHODS:
      Descriptive analysis of reported cases and case - control exposure to the
      implicated food. The variables taken into account were age, sex, symptoms and
      start date. Sources of information used were the records of the SVEA and
      individual digital report (DIRAYA). Frequencies and attack rates were calculated,
      and a Bayesian analysis for the comparison of difference in proportions of
      disease was carried out for a 95% probability or credibility range (IP). RESULTS:
      Among the 130 attendees at a communion 41 cases of tonsillopharyngitis (attack
      rate 31.5%) were detected, and in smears Group A Beta-Hemolytic Streptococcus was
      isolated. The most affected age group was the 25-44 year-olds, 16 (39,0%); 68.6%
      (24) female. The egg salad showed a probability greater than 80% P(Delta>0.10 and
      Delta>0.15) for a 95% IP of risk of disease after intake and a probability of
      having a lower risk of no disease. CONCLUSIONS: It was a Group A Beta-Hemolytic
      Streptococcal outbreak, the epidemiological evidence indicates exposure to common
      single source, hence the hypothesis of dietary origin, the implicated food was
      egg salad. Contributing factors could be cross-contamination after preparation
      favoured by the bad practice and the conditions of the place.

PMID- 22392470
TI  - [Evaluation of a medical records archive through the application of statistical
      methods for quality control].
AB  - BACKGROUND: In undertaking a Minimum Basic Data Set (MBDS) of hospital discharges
      has to be done for all hospitals. It depends on the good function of the Medical
      Records Archive. The objective of this study is the continuous evaluation of the
      quality of the Medical Records Archive via Control Diagrams statistical
      techniques arose. METHODS: From June 2005 to January 2009 a retrospective search
      of the discharges/Medical Records pending coding, from a tertiary care university
      hospital was carried out. The different categories of discharges/Medical Records
      were registered on an Excel spreadsheet under the following headings: searched
      for, found, completed/closed, pending and not located for each a particular month
      and year. The Overall Effectiveness Index was calculated, 0,9 being the standard
      quality value. Furthermore to assess the process quality over the entire length
      of the period studied and in each month and year, the Shewhart's Control Diagram
      and Cumulative Sum (CUSUM) graphic tests were applied. RESULTS: The Overall
      Effectiveness Index was 0.95. The majority of % errors corresponded to November
      2008 with 55 (11.73%) and June 2008 with 14 (10.45%). In the Control Diagrams
      there are abnormally high values, obtained after standardization, in July 2005
      (5.95) and November 2008 (7.00). The CUSUM showed one point outside of the
      initial control (July 2005 - 5.95), although until June 2007, the average (4.7%)
      was slightly below the overall averages (4.81%) and then increases from July 2007
      on (5.02%). CONCLUSION: The Archive quality has varied over time, demonstrating
      that it was especially lower at the end of the study.

PMID- 22392472
TI  - [Public health and forensic pathology].

PMID- 22392471
TI  - [Construction and validation of a self-efficacy scale for physical activity].
AB  - BACKGROUND: The estimation by standardized tests on belief in personal capacity
      to practice regular physical activity (self-efficacy for physical activity)
      allows us to make predictions about the actual practice of this behavior. We do
      not have measuring instruments suitable for this purpose, therefore, we propose
      to construct and validate a scale to determine levels of self-efficacy of adult
      users of the Primary Health Care Services for regular physical activity. METHODS:
      Phases: 1) Develop and review the scale by expert judges. 2) A pilot study. 3)
      Determination of reliability and validity of the test. The sample was 388 adult
      users (18-65 years) of health centres from the province of Seville selected by
      cluster sampling (health centres) and quotas (town size, age and sex). Concurrent
      validity was found by the International Physical Activity Questionnaire (IPAQ)
      and discriminant validity by Beck Depression Inventory (BDI). RESULTS: The
      results reported adequate content validity and high reliability (Cronbach Alpha >
      0,9 in all factors and beta = 0,96). Exploratory factor analysis showed three
      factors explaining 52,569% of the variance. The scale was sensitive to activity
      levels assessed by the IPAQ (F (1)= 4.131; p <0.05) and negatively correlated
      with BDI (r = -0,127; p <0,05). CONCLUSIONS: The psychometric properties of the
      scale are appropriate for measuring the efficacy of adult users of Health
      Services to practice regular physical activity.

PMID- 22392473
TI  - Steered molecular dynamics simulation study on dynamic self-assembly of single
      stranded DNA with double-walled carbon nanotube and graphene.
AB  - In the present work, we explored the diameter selectivity of dynamic self
      assembly for the single-strand DNA (ssDNA) encapsulation in double-walled
      nanotubes (DWNTs) via molecular dynamics simulation method. Moreover, the pulling
      out process was carried out by steered molecular dynamics simulations.
      Considering pi-pi stacking and solvent accessibility together, base-CNT binding
      should be strongest on a graphene sheet and weakest on the inner CNT surface.
      When pulling the ssDNA out of the single-walled carbon nanotube (SWNT), the force
      exhibits characteristic fluctuations around a plateau about 300 pN. Each
      fluctuation force pulse to pull ssDNA corresponds to the exit of one base. In
      addition, the solvents used for the system are also of significant interest.
      Water does play an important role in encapsulation process but doesn't in the
      pulling out process.

PMID- 22392474
TI  - Invited commentary: Structure and context matters--the need to emphasize "social"
      in "psychosocial epidemiology".
AB  - A high level of influence on core aspects of life in general and at the workplace
      in particular is believed to reduce the risk of ill health. In this issue of the
      Journal, Joensuu et al. (Am J Epidemiol. 2012;175(7):609-619) shake this belief
      by presenting prospective associations between high decision authority at work
      and increased all-cause, cardiovascular, and alcohol-related mortality among
      Finnish forest company employees followed through 2005. In this invited
      commentary, the author welcomes these findings as a much needed inspiration for
      reflections on the current state of psychosocial epidemiology and how it can be
      advanced in the future. Although it is important to investigate possible harmful
      effects of too high decision authority, the author argues that it is even more
      important to be aware that psychosocial factors originate from societal
      structures and social contexts. Understanding these structures and contexts,
      their changes over time, and their relation to psychosocial factors is key for
      understanding the effect of psychosocial factors on health and illness. Joensuu
      et al. have presented thought-provoking findings. It is the hope of the author
      that this will push the research community to emphasize the "social" in
      "psychosocial epidemiology."

PMID- 22392475
TI  - Differential associations of job control components with mortality: a cohort
      study, 1986-2005.
AB  - Inconsistent evidence of the hypothesized favorable effects of high job control
      on health may have resulted from a failure to treat job control as a multifactor
      concept. The authors studied whether the 2 components of job control, decision
      authority and skill discretion, were differentially associated with cause
      specific mortality in 13,510 Finnish forest company employees with no history of
      severe illness. Surveys on work characteristics were carried out in 1986 and
      1996, and the respondents were followed up until the end of 2005 by use of the
      Statistics Finland National Death Registry. During a mean follow-up of 15.5
      years, 981 participants died. In the analyses adjusted for confounders, employees
      with high and intermediate levels of skill discretion had a lower all-cause
      mortality risk than those with low skill discretion, with hazard ratios of 0.84
      (95% confidence interval (CI): 0.69, 1.02) and 0.81 (95% CI: 0.69, 0.96),
      respectively. In contrast, high decision authority was associated with elevated
      risks of all-cause, cardiovascular, and alcohol-related mortality, with hazard
      ratios of 1.28 (95% CI: 1.06, 1.54), 1.49 (95% CI: 1.11, 2.02), and 2.03 (95% CI:
      1.03, 4.00), respectively. The results suggest that job control is not an
      unequivocal concept in relation to mortality; decision authority and skill
      discretion show different and to some extent opposite associations.

PMID- 22392476
TI  - Response to invited commentary: Joensuu et al. respond to "Structure and context
      matters".

PMID- 22392477
TI  - QM/MM investigations of organic chemistry oriented questions.
AB  - About 35 years after its first suggestion, QM/MM became the standard theoretical
      approach to investigate enzymatic structures and processes. The success is due to
      the ability of QM/MM to provide an accurate atomistic picture of enzymes and
      related processes. This picture can even be turned into a movie if nuclei
      dynamics is taken into account to describe enzymatic processes. In the field of
      organic chemistry, QM/MM methods are used to a much lesser extent although almost
      all relevant processes happen in condensed matter or are influenced by
      complicated interactions between substrate and catalyst. There is less importance
      for theoretical organic chemistry since the influence of nonpolar solvents is
      rather weak and the effect of polar solvents can often be accurately described by
      continuum approaches. Catalytic processes (homogeneous and heterogeneous) can
      often be reduced to truncated model systems, which are so small that pure quantum
      mechanical approaches can be employed. However, since QM/MM becomes more and more
      efficient due to the success in software and hardware developments, it is more
      and more used in theoretical organic chemistry to study effects which result from
      the molecular nature of the environment. It is shown by many examples discussed
      in this review that the influence can be tremendous, even for nonpolar reactions.
      The importance of environmental effects in theoretical spectroscopy was already
      known. Due to its benefits, QM/MM can be expected to experience ongoing growth
      for the next decade.In the present chapter we give an overview of QM/MM
      developments and their importance in theoretical organic chemistry, and review
      applications which give impressions of the possibilities and the importance of
      the relevant effects. Since there is already a bunch of excellent reviews dealing
      with QM/MM, we will discuss fundamental ingredients and developments of QM/MM
      very briefly with a focus on very recent progress. For the applications we follow
      a similar strategy.

PMID- 22392478
TI  - Paramagnetic solid-state magic-angle spinning NMR spectroscopy.
AB  - A number of technical improvements have recently opened up solid-state NMR to the
      analysis of new classes of substrates with wide ranging implications for
      molecular and biological sciences, with an immediate impact on a large community
      of researchers. A wealth of information can be extracted from the analysis of
      solid-state NMR signals of paramagnetic compounds, as the changes induced by the
      paramagnetic center depend in a well-defined way on the structure of the
      molecule. Solid-state NMR is in a position to allow direct, straightforward
      experimental access to the fine details of the molecular electronic
      configuration, which is in turn a sensible reporter of the molecular geometry in
      small catalysts as well as in larger biomolecules.

PMID- 22392479
TI  - Stereoselective synthesis of tetrasubstituted alkenes via torquoselectivity
      controlled olefination of carbonyl compounds with ynolates.
AB  - The efficient synthesis of tetrasubstituted alkenes by the olefination of
      carbonyl compounds with ynolates is described. This reaction involves the
      cycloaddition of ynolates with carbonyl groups, followed by electrocyclic ring
      opening of the resulting beta-lactone enolates. Orbital symmetry during the
      electrocyclic ring opening requires conrotatory motion. The direction of this
      rotation (inward or outward) determines the E/Z geometry to the tetrasubstituted
      olefin product through torquoselectivity. Theoretical calculations revealed that
      several secondary orbital interactions are essential for the high
      torquoselectivity. This methodology is a novel olefination for constructing
      multisubstituted olefins.

PMID- 22392480
TI  - Stereoselective synthesis of Z-alkenes.
AB  - This chapter offers a general review of the evolvement of methods for the
      stereoselective synthesis of Z-alkenes, with a focus on the development of
      catalytic systems towards this goal in recent years.

PMID- 22392481
TI  - SHG nanoprobes: advancing harmonic imaging in biology.
AB  - Second harmonic generating (SHG) nanoprobes have recently emerged as versatile
      and durable labels suitable for in vivo imaging, circumventing many of the
      inherent drawbacks encountered with classical fluorescent probes. Since their
      nanocrystalline structure lacks a central point of symmetry, they are capable of
      generating second harmonic signal under intense illumination - converting two
      photons into one photon of half the incident wavelength - and can be detected by
      conventional two-photon microscopy. Because the optical signal of SHG nanoprobes
      is based on scattering, rather than absorption as in the case of fluorescent
      probes, they neither bleach nor blink, and the signal does not saturate with
      increasing illumination intensity. When SHG nanoprobes are used to image live
      tissue, the SHG signal can be detected with little background signal, and they
      are physiologically inert, showing excellent long-term photostability. Because of
      their photophysical properties, SHG nanoprobes provide unique advantages for
      molecular imaging of living cells and tissues with unmatched sensitivity and
      temporal resolution.

PMID- 22392482
TI  - Synthetic lethality of PARP inhibition in BRCA-network disrupted tumor cells is
      associated with interferon pathway activation and enhanced by interferon-gamma.
AB  - Tumor suppressor genes BRCA1 and BRCA2 function in a complex gene network that
      regulates homologous recombination and DNA double-strand break repair. Disruption
      of the BRCA-network through gene mutation, deletion, or RNAi-mediated silencing
      can sensitize cells to small molecule inhibitors of poly (ADP-ribose) polymerase
      (PARPi). Here, we demonstrate that BRCA-network disruption in the presence of
      PARPi leads to the selective induction and enhancement of interferon pathway and
      apoptotic gene expression in cultured tumor cells. In addition, we report PARPi
      cytotoxicity in BRCA1-deficient tumor cells is enhanced >10-fold when combined
      with interferon-gamma. These findings establish a link between synthetic
      lethality of PARPi in BRCA-network disrupted cells and interferon pathway
      activation triggered by genetic instability.

PMID- 22392483
TI  - Role of mitochondrial pathway in compression-induced apoptosis of nucleus
      pulposus cells.
AB  - Various mechanical stresses can induce apoptosis of nucleus pulposus (NP) cells
      and intervertebral disc (IVD) degeneration in vivo, but the underlying molecular
      mechanism by which the number of NP cells is decreased in degenerated IVD is
      still not elucidated. The purpose of this study was to investigate whether the
      mitochondrial pathway is involved in compression-induced apoptosis of rabbit NP
      cells. The compression apparatus was used to investigate the effect of the
      compression in this process at one magnitude (1.0 MPa) for 6, 12, 18, 24 and 36
      h. Cell viability was measured by cell counting kit-8. Apoptosis rate was
      analyzed by flow cytometry and the morphologic changes in apoptosis cells were
      observed by the phase-contrast microscopy and Hoechst 33258 staining. The
      apoptosis-related gene and protein synthesis, such as Bax, Bcl-2 and Caspase-3,
      was analyzed by real-time polymerase chain reaction and Western-blot,
      respectively. Mitochondrial function was evaluated by analyzing the mitochondrial
      permeability transition pore (MPTP), as well as reactive oxygen species (ROS) and
      mitochondrial membrane potential (MMP). The results indicated that compression at
      the magnitude of all time points induced apoptosis of rabbit NP cells in a time
      dependent manner, and the cell viability was reduced significantly. Furthermore,
      the compression at this level profoundly suppressed the functions of the
      mitochondria such as the opening of MPTP, the excessive production of ROS and the
      decreased MMP. Our findings suggest that the compression-induced IVD degeneration
      is mediated, at least in part, via the mitochondrial apoptotic pathway in NP
      cells.

PMID- 22392484
TI  - Serous papillary adenocarcinoma probably arising from epithelial inclusions of
      the hepatic hilar lymph node.
AB  - BACKGROUND: Only three cases of serous adenocarcinoma arising from Mullerian
      epithelial inclusions of the lymph node have been reported. Herein reported is a
      case of serous papillary adenocarcinoma arising probably from epithelial
      (Mullerian) inclusions of the hepatic hilar lymph node. CASE REPORT: A 73-year
      old woman presented with peripheral neuropathy, which was thought to be a
      paraneoplastic syndrome associated with visceral malignancy. Total body
      examination, including X-P, US, CT, MRI, PET, and upper and lower
      gastrointestinal endoscopy was done. As the results, only lymph node swelling was
      detected in the hepatic hilus. Tumor was not identified in other sites. The
      physicians considered malignant lymphoma, and laparotomic excision of the hepatic
      hilar mass was performed. Cytological examination of abdominal cavity washing
      revealed no malignant cells. Grossly, the mass was firm and white and measured 4
      * 5 * 5 cm. Microscopically, the mass showed carcinoma cells arranged in
      papillary and tubular patterns. The appearances strongly resembled serous
      papillary adenocarcinoma of the ovary. Lymph node structures were noted in some
      peripheral areas. No benign epithelial inclusions were recognized.
      Immunohistochemically, the carcinoma cells were positive for ER, PgR, CA125, WT1,
      p53. They were negative for TTF-1 and CDX-2. Because the positive ER, PgR, CA125,
      WT1, p53 and p16 are indicative of gynecologic malignancy, simple hysterectomy
      and bilateral salpingo-oophorectomy were performed, which showed no
      abnormalities. Cytological examination of abdominal cavity washing fluid revealed
      no malignant cells. The patient was treated by paclitaxel and carboplatin, and is
      now alive without metastasis 2 years after the first manifestation. CONCLUSION:
      The author reported a case of serous papillary adenocarcinoma arising probably
      from epithelial (Mullerian) inclusions of the hepatic hilar lymph node.

PMID- 22392485
TI  - Clomiphene citrate alternatives for the initial management of polycystic ovary
      syndrome: an evidence-based approach.
AB  - Polycystic ovary syndrome (PCOS) is a prevalent and heterogeneous condition
      affecting 4-8% of reproductive age women. It is the most common cause of chronic
      anovulation and is associated with hyperandrogenemia. Clomiphene citrate (CC) is
      considered as the first-line therapy for ovulation induction in these patients.
      Despite progress in understanding the pathophysiology of PCOS over the past 20
      years, many questions persist to the extent that PCOS was described as "A Riddle
      Wrapped in a Mystery inside an Enigma". On the other hand, a recent publication
      from the Centers for Disease Control suggested that CC may be associated with an
      increased risk of birth defects. The purpose of this review is to critically
      evaluate and summarize the current literature regarding CC alternatives for the
      initial management of PCOS focusing specifically on the roles of weight loss and
      other approaches to ovulation induction as insulin-sensitizing drugs, aromatase
      inhibitors, minimal stimulation protocol, gonadotrophins and surgery
      (laparoscopic ovarian drilling). Finally, the efficacy of intrauterine
      insemination with CC for the initial management of PCOS will be evaluated.

PMID- 22392486
TI  - Association between endometriosis and polymorphisms in tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL), TRAIL receptor and osteoprotegerin
      genes and their serum levels.
AB  - PURPOSE: To evaluate the relationship between endometriosis and polymorphisms in
      the genes encoding tumor necrosis factor (TNF)-related apoptosis-inducing ligand
      (TRAIL), TRAIL receptor (DR) and osteoprotegerin (OPG) and their serum levels in
      Korean women. METHODS: A case-control study was conducted with 138 women with
      endometriosis and 214 women without endometriosis in academic medical center.
      TRAIL c.49G>A, c.592A>G, c.615A>G, and c.662T>C; DR4 c.626G>C and c.1322A>G; DR5
      c.95C>T, c.200C>T, and c.72T>G; OPG -245T>G, c.9C>G, c.788A>C, and c.9938G>T
      polymorphisms were investigated and circulating levels of TRAIL and OPG were
      measured. RESULTS: The TRAIL c.49G>A, c.615A>G, and c.662T>C; the DR4 c.626G>C;
      the DR5 c.72T>G; the OPG c.788A>C and c.9938G>T polymorphisms were not observed.
      The genotype distributions and allele frequencies of single or combined
      polymorphisms of TRAIL, DR4, DR5, and OPG measured in women with endometriosis
      were not different from those in women without endometriosis, regardless of
      endometriosis stage. Serum TRAIL and OPG levels were significantly lower in women
      with endometriosis than in women without endometriosis, but these levels did not
      show differences between early and advanced endometriosis. CONCLUSIONS:
      Endometriosis is associated with circulating TRAIL and OPG levels in Korean women
      but not with the TRAIL, DR, and OPG polymorphisms.

PMID- 22392487
TI  - Vascular endothelial growth factor gene polymorphisms and endometriosis risk: a
      meta-analysis.
AB  - PURPOSE: The vascular endothelial growth factor (VEGF) gene polymorphism has been
      reported to be associated with endometriosis risk. The purpose of the present
      study was to perform a comprehensive meta-analysis to explore whether VEGF gene
      polymorphisms confer risk to endometriosis. METHODS: By searching PubMed and
      EMBASE databases, a total of 11 studies were identified. Crude odds ratio (OR)
      and their corresponding 95% confidence intervals (CI) for VEGF gene polymorphisms
      and endometriosis risk were calculated. RESULT: An association of VEGF gene
      +936TC polymorphism with endometriosis was found (Fixed-effect model: TT + TC vs.
      CC: OR 1.184, 95% CI 1.027-1.366, P = 0.020; TC vs. CC: OR 1.187, 95% CI 1.024
      1.375, P = 0.023. Random-effect model: TT + TC vs. CC: OR 1.203, 95% CI 1.003
      1.443, P = 0.046; TC vs. CC: OR 1.188, 95% CI 1.021-1.382, P = 0.026). No
      association between VEGF genes -460CT, +405CG, -2578AC, -1154GA polymorphisms and
      endometriosis was observed. CONCLUSION: Our results indicate that VEGF +936TC
      gene polymorphism is a risk factor for endometriosis, and not -460CT, +405CG, 
      2578AC, -1154GA.

PMID- 22392488
TI  - What every gynecologist should know about male infertility: an update.
AB  - PURPOSE: Our article reviews the evolving concepts in the field of male
      infertility for gynecologists and other health professionals involved in the care
      of men and women experiencing difficulty in having a child. The increased
      knowledge will help in the better management and treatment of infertile couples.
      METHODS: Review of literature through Pubmed, Science Direct, Online Library.
      RESULTS: Gynecologists are often the first healthcare providers to assess an
      infertile couple. Because half of all infertility problems stem from male
      factors, it is crucial for the gynecologist to remain updated on the main
      conditions that cause male infertility as well as current diagnostic tools and
      treatment options, including conventional strategies and assisted reproductive
      techniques. CONCLUSIONS: Extraordinary advances have been achieved in the field
      of male infertility over the past several years and many old concepts are now
      challenged. Therefore, it is imperative that male infertility physicians should
      update the gynecologists about the recent advances in the work-up of infertile
      men in terms of diagnosis and management. Such convention will help improve the
      standards of care for the infertile couple and enhance the cooperation between
      male and female reproductive endocrinologists.

PMID- 22392489
TI  - c-Kit proto-oncogene expression in endometrial hyperplasia and endometrial
      cancer.
AB  - PURPOSE: To evaluate the expression of c-kit (CD117) in endometrial hyperplasia
      and endometrial cancer. METHODS: Expression of c-kit in 10 normal endometrium, 18
      simple endometrial hyperplasia, 16 complex endometrial hyperplasia (10 cases with
      atypia and 6 cases without atypia), and 6 endometrial cancer were investigated by
      immunohistochemistry. RESULTS: c-Kit expression decreased as the lesion
      progressed to endometrial cancer. Immunostaining was mostly focal and weak in the
      normal endometrium and was mostly diffuse and strong in the simple and complex
      endometrial hyperplasia. CONCLUSIONS: Simple and complex hyperplastic endometrial
      tissues express diffuse cytoplasmic staining for c-kit and the expression
      decreases with the progression of the lesion.

PMID- 22392490
TI  - Prenatal diagnosis and outcome of multiple pregnancies with reversed arterial
      perfusion (TRAP-sequence).
AB  - OBJECTIVES: We analyse the prenatal detection and pregnancy outcome of twin
      reversed arterial perfusion syndrome (TRAP-sequence) in monochorionic twin
      pregnancies. METHODS: We included all cases in which the prenatal diagnosis of a
      TRAP-sequence had been established and reviewed the prenatal, obstetrical, and
      pathological records of the acardiac twin as well as the neonatal/pediatric
      records of the donor twin. Minimal follow-up for the donor twin after birth was 6
      months. RESULTS: We detected six cases of TRAP-sequence in 412 examined
      monochorionic multiple pregnancies (incidence 1.46%) Mean gestational age at
      diagnosis was 20.4 (13.1-28.0) gestational weeks. All donor twins survived
      without detectable mid- or long-term sequelae. There was neither missed prenatal
      diagnosis nor a false-positive diagnosis of TRAP-sequence. Mean birthweight of
      the acardiac twins was 1,400 g (830-2800 g). There was an uneventful medical
      history in the maternal records of all included women. Fetal karyotype was
      available for 5/6 twin-pairs, all revealing a normal distribution of the
      chromosomes. All acardiac twins had post-mortem examination with specification of
      the subtypes of acardiac twin displaying 3/6 acardius acephalus, 2/6 acardius
      amorphus, and 1/6 acardius anceps. CONCLUSIONS: The antenatal diagnosis of TRAP
      sequence is feasible and can be established during the first-trimester-screening.
      The discrimination of the adequate time to end the pregnancy, though a crucial
      concern, remains a challenging question. Future studies should address this
      topic.

PMID- 22392491
TI  - Transvaginal 3D HD-flow in diagnosis of uterine arteriovenous malformation.

PMID- 22392492
TI  - Favorable prognosis in patients with T1a/T1bN0 triple-negative breast cancers
      treated with multimodality therapy.
AB  - BACKGROUND: The authors evaluated the clinical characteristics, natural history,
      and outcomes of patients who had <=1 cm, lymph node-negative, triple-negative
      breast cancer (TNBC). METHODS: After excluding patients who had received
      neoadjuvant therapy, 1022 patients with TNBC who underwent definitive breast
      surgery during 1999 to 2006 were identified from an institutional database. In
      total, 194 who had lymph node-negative tumors that measured <=1 cm comprised the
      study population. Clinical data were abstracted, and survival outcomes were
      analyzed. RESULTS: The median follow-up was 73 months (range, 5-143 months). The
      median age at diagnosis was 55.5 years (range, 27-84 years). Tumor (T)
      classification was microscopic (T1mic) in 16 patients (8.2%), T1a in 49 patients
      (25.3%), and T1b in 129 patients (66.5%). Most tumors were poorly differentiated
      (n = 142; 73%), lacked lymphovascular invasion (n = 170; 87.6%), and were
      detected by screening (n = 134; 69%). In total, 129 patients (66.5%) underwent
      breast-conserving surgery, and 65 patients (33.5%) underwent mastectomy. One
      hundred thirteen patients (58%) received adjuvant chemotherapy, and 123 patients
      (63%) received whole-breast radiation. The patients who received chemotherapy had
      more adverse clinical and disease features (younger age, T1b tumor, poor tumor
      grade; all P < .05). Results from testing for the breast cancer (BRCA)
      susceptibility gene were available for 49 women: 19 women had BRCA1 mutations, 7
      women had BRCA2 mutations, and 23 women had no mutations. For the entire group,
      the 5-year local recurrence-free survival rate was 95%, and the 5-year distant
      metastasis-free survival rate was 95%. There was no difference between patients
      with T1mic/T1a tumors and patients with T1b tumors in the distant recurrence rate
      (94.5% vs 95.5%, respectively; P = .81) or in the receipt of chemotherapy (95.9%
      vs 94.5%, respectively; P = .63). CONCLUSIONS: Excellent 5-year locoregional and
      distant control rates were achievable in patients with TNBC who had tumors <=1.0
      cm, 58% of whom received chemotherapy. These results identified a group of
      patients with TNBC who had favorable outcomes after early detection and
      multimodality treatment.

PMID- 22392493
TI  - Viral infection: SAMHD1 cuts the power to HIV-1.

PMID- 22392494
TI  - Immune evasion: Gm18, a bacterial 'invisibility cloak'.

PMID- 22392495
TI  - Antimicrobials: Making a fus over FA.

PMID- 22392496
TI  - Increased antioxidant content in juice enriched with dried extract of pomegranate
      (Punica granatum) peel.
AB  - Antioxidants are compounds responsible for free radical scavenging in the body.
      They protect the organism from oxidative modification of cells and tissues. These
      modifications have been associated with degenerative diseases, atherosclerosis
      and carcinogenesis. Punica granatum displays high antioxidant potential due to
      the presence of phenolic compounds, which are capable of disease prevention. The
      present study showed the highest antioxidant activity in pomegranate peel than in
      seeds and pulp. Based on these results, pomegranate peel was used to produce
      dried extract that was added to commercial tomato juice and orange juice with
      strawberries. Analysis to determine the content of phenolic compounds and
      antioxidant activity was performed on pomegranate pulp, seeds and peel and in
      juices enriched with dried extract of pomegranate peel. The dried extract was
      responsible for a significant increase in antioxidant activity of the juices,
      proportional to the concentrations added. However, although both flavors of
      enriched juices displayed high antioxidant levels, the samples with higher dried
      extract concentrations received the lowest scores from sensory analysis
      participants due to the characteristic astringent flavor of pomegranate peels.
      Therefore, to obtain greater acceptance in the consumer market, we concluded that
      the maximum addition of dried pomegranate peel extract is 0.5% in tomato juice
      and orange juice with strawberries.

PMID- 22392497
TI  - Circulating salicylic acid and metabolic and inflammatory responses after fruit
      ingestion.
AB  - We hypothesized that fruit ingestion provides measurable amounts of salicylic
      acid (SA) and produces different metabolic and inflammatory responses compared to
      mere fruit sugars. In a randomized-crossover study, 26 healthy subjects received
      a peach shake meal (PSM) (SA: 0,06 +/- 0,001 mg/100 g) and a mixed sugar meal
      (MSM), consisting in an aqueous solution with the same sugars found in the peach
      shake. In order to control for the SA contribution from meals in the previous
      day, 16 subjects (Group 1) abstained from fruits and vegetables consumption the
      evening before trials, and 10 subjects (Group 2) maintained their usual diet.
      Circulating SA, glucose, insulin, free fatty acids, and interleukin-6 were
      determined. Basal SA was lower in Group 1 than in Group 2 (0.09 +/- 0.02 vs. 0.30
      +/- 0.03 MUmol/l, p < 0.001), peaked at 90 min in both groups (0.18 +/- 0.01 vs.
      0.38 +/- 0.02 MUmol/l, p < 0.01) and remained above baseline (p < 0.05) up to 3
      h. Glycemia increased less after PSM at 15 min (p < 0.01) with a lower average
      glucose excursion (p < 0.05). Insulin peaked at 45 min with both meals but
      decreased less rapidly with PSM. Free fatty acids decreased more (p < 0.01), and
      interleukin-6 increased less (p < 0.05) with PSM. Dietary fruit intake increases
      the concentration of SA in vivo, and provides non-nutrients capable to modulate
      the inflammatory and metabolic responses to carbohydrates.

PMID- 22392498
TI  - Potato- an important source of nutritional kynurenic acid.
AB  - Kynurenic acid (KYNA) is a metabolite of tryptophan which is formed along the
      kynurenine pathway. KYNA may possess neuroprotective, anti-inflammatory,
      antioxidant and antiproliferative properties. This study measured the
      concentration of KYNA in various varieties of potatoes and products made from
      potatoes. KYNA content was determined by means of the high-performance liquid
      chromatography with fluorescence detection. KYNA was found in all 16 studied
      varieties of potato tubers in amounts varying from 0.239 to 3.240 MUg/g dry
      weight. The content of KYNA in potato tubers declined during long-term storage.
      The content of KYNA in French fries varied from 0.100 to 0.646 MUg/g dry weight.
      KYNA content in potato crisps was 0.478 and 0.576 MUg/g dry weight. Hence, all in
      all, we concluded that the amount of KYNA potentially delivered to the human body
      in potatoes and various foods produced from potatoes is high and might be
      compared to the amount of KYNA present in a maximum daily dose of popular herbs
      and herbal medicines.

PMID- 22392499
TI  - ImmunoPET using engineered antibody fragments: fluorine-18 labeled diabodies for
      same-day imaging.
AB  - Combining the specificity of tumor-targeting antibodies with the sensitivity and
      quantification offered by positron emission tomography (PET) provides tremendous
      opportunities for molecular characterization of tumors in vivo. Until recently,
      significant challenges have been faced when attempting to combine antibodies
      which show long biological half-lives and positron-emitting radionuclides with
      comparably short physical half-lives, in particular (18)F (half-life, 109 min). A
      fast and simple microwave-assisted method of generating N-succinimidyl-4
      [(18)F]fluorobenzoate has been developed and employed for radiolabeling a small,
      rapidly targeting HER2-specific engineered antibody fragment, the cys-diabody.
      Using this tracer, HER2-positive tumor xenografts in mice were detected at 1-4 h
      post-injection by microPET. This confirms the rapid kinetics of
      [(18)F]fluorobenzoyl cys-diabody localization, and demonstrates the feasibility
      of same-day immunoPET imaging. This approach can be broadly applied to antibodies
      targeting cell surface biomarkers for molecular imaging of tumors and should be
      highly translatable for clinical use.

PMID- 22392500
TI  - Cell surface expression of hyaluronan on human ovarian cancer cells inversely
      correlates with their adhesion to peritoneal mesothelial cells.
AB  - Eight of 15 human ovarian carcinoma cell lines were shown to express high levels
      of hyaluronan (HA) on their surfaces. The role of cell surface HA in its adhesion
      to mesothelial cells, which is potentially involved in peritoneal dissemination,
      was evaluated. Three human ovarian carcinoma cell lines, ES-2, MH, and KF cells,
      were repeatedly sorted into variant cell lines with high levels of cell surface
      HA (ES-2/HA+7, MH/HA+7, and KF/HA+7) and with low cell surface HA (ES-2/HA-7,
      MH/HA-7, and KF/HA-7). The ability of these cells to adhere to peritoneal
      mesothelial cells was compared. ES-2/HA+7, MH/HA+7, and KF/HA+7 cells were less
      adherent to mesothelial cells than the ES-2/HA-7, MH/HA-7, and KF/HA-7 cells. On
      ovarian carcinoma cells, high cell surface HA levels seem to inversely correlate
      with their capacity to adhere and disseminate to the peritoneum. Considering that
      peritoneum implantation is the primary ovarian cancer complication, HA cell
      surface expression may be considered a property associated with a less aggressive
      phenotype, which is contrary to the general perception that HA expression is
      associated with malignant progression.

PMID- 22392501
TI  - Effects of BTG2 on proliferation inhibition and anti-invasion in human lung
      cancer cells.
AB  - The objective of the study was to investigate the impact of the B cell
      translocation gene 2 (BTG2) on lung cancer cell growth, proliferation,
      metastasis, and other biological characteristics and to provide experimental
      evidence for the biological treatment of human lung cancer. A pcDNA3.1-BTG2
      eukaryotic expression vector was constructed and transfected into the human lung
      cancer cell line A549. The biological changes in the BTG2-expressing cells were
      analyzed using growth curves, the MTT (tetrazolium) assay, propidium iodide (PI)
      staining, and the Transwell invasion chamber. Additionally, Western blotting was
      used to determine the impact of BTG2 on the protein expression of cyclin D1, MMP
      1, and MMP-2. Compared to the empty vector-transfected A549 cells or the mock
      transfected A549 cells, the pcDNA3.1-BTG2-transfected A549 cells grew
      significantly slower. No significant differences were detected between the empty
      vector-transfected group and the mock-transfected A549 cells. The growth curve
      analysis and the PI staining showed that the pcDNA3.1-BTG2-transfected cells grew
      significantly slower than the empty vector-transfected A549 cells (P < 0.05). The
      cell invasion assay results suggested that the invasion rate of the pcDNA3.1-BTG2
      transfected A549 cells was significantly slower than the invasion rate of the
      empty vector-transfected group and the mock-transfected group (P < 0.05). The
      overexpression of BTG2 may inhibit the protein expression of cyclin D1, MMP-1,
      and MMP-2 in A549 cells. The overexpression of BTG2 may inhibit the growth,
      proliferation, and invasiveness of the A549 human lung cancer cell line.

PMID- 22392502
TI  - Variety in vegetable and fruit consumption and the risk of gastric and esophageal
      cancer in the European Prospective Investigation into Cancer and Nutrition.
AB  - Diets high in vegetables and fruits have been suggested to be inversely
      associated with risk of gastric cancer. However, the evidence of the effect of
      variety of consumption is limited. We therefore investigated whether consumption
      of a variety of vegetables and fruit is associated with gastric and esophageal
      cancer in the European Prospective Investigation into Cancer and Nutrition study.
      Data on food consumption and follow-up on cancer incidence were available for
      452,269 participants from 10 European countries. After a mean follow-up of 8.4
      years, 475 cases of gastric and esophageal adenocarcinomas (180 noncardia, 185
      cardia, gastric esophageal junction and esophagus, 110 not specified) and 98
      esophageal squamous cell carcinomas were observed. Diet Diversity Scores were
      used to quantify the variety in vegetable and fruit consumption. We used
      multivariable Cox proportional hazard models to calculate risk ratios.
      Independent from quantity of consumption, variety in the consumption of
      vegetables and fruit combined and of fruit consumption alone were statistically
      significantly inversely associated with the risk of esophageal squamous cell
      carcinoma (continuous hazard ratio per 2 products increment 0.88; 95% CI 0.79
      0.97 and 0.76; 95% CI 0.62-0.94, respectively) with the latter particularly seen
      in ever smokers. Variety in vegetable and/or fruit consumption was not associated
      with risk of gastric and esophageal adenocarcinomas. Independent from quantity of
      consumption, more variety in vegetable and fruit consumption combined and in
      fruit consumption alone may decrease the risk of esophageal squamous cell
      carcinoma. However, residual confounding by lifestyle factors cannot be excluded.

PMID- 22392503
TI  - Role of the CCL21 and CCR7 pathways in rheumatoid arthritis angiogenesis.
AB  - OBJECTIVE: To determine the role of CCL21 and its receptor CCR7 in the
      pathogenesis of rheumatoid arthritis (RA). METHODS: Histologic studies were
      performed to compare the expression of CCR7 and CCL21 in RA synovial tissue.
      Next, the role of CCL21 and/or CCR7 in angiogenesis was examined using in vitro
      chemotaxis, tube formation, and in vivo Matrigel plug assays. Finally, the
      mechanism by which CCL21 mediates angiogenesis was determined by Western blot
      analysis and endothelial cell chemotaxis and tube formation assays. RESULTS:
      CCL21, but not CCL19, at concentrations present in the RA joint, induced human
      microvascular endothelial cell (HMVEC) migration that was mediated through CCR7
      ligation. Suppression of the phosphatidylinositol 3-kinase pathway markedly
      reduced CCL21-induced HMVEC chemotaxis and tube formation; however, suppression
      of the ERK and JNK pathways had no effect on these processes. Neutralization of
      either CCL21 in RA synovial fluid or CCR7 in HMVECs significantly reduced the
      induction of HMVEC migration and/or tube formation by RA synovial fluid. We
      further demonstrated that CCL21 is angiogenic, by showing its ability to promote
      blood vessel growth in Matrigel plugs in vivo at concentrations that are present
      in RA joints. CONCLUSION: Angiogenesis is dependent on endothelial cell
      activation, migration, and proliferation, and inhibition of angiogenesis may
      provide a novel therapeutic approach in RA. This study identified a novel
      function of CCL21 as a mediator of RA angiogenesis, supporting CCL21/CCR7 as a
      therapeutic target in RA.

PMID- 22392504
TI  - Prothrombin Mumbai causes severe prothrombin deficiency due to a novel Cys90Ser
      mutation.

PMID- 22392505
TI  - Congenital myopathies: an update.
AB  - Congenital myopathy is a clinicopathological concept of characteristic
      histopathological findings on muscle biopsy in a patient with early-onset
      weakness. Three main categories are recognized within the classical congenital
      myopathies: nemaline myopathy, core myopathy, and centronuclear myopathy. Recent
      evidence of overlapping clinical and histological features between the classical
      forms and their different genetic entities suggests that there may be shared
      pathomechanisms between the congenital myopathies. Animal models, especially
      mouse and zebrafish, have been especially helpful in elucidating such
      pathomechanisms associated with the congenital myopathies and provide models in
      which future therapies can be investigated.

PMID- 22392506
TI  - Disorders of the optic nerve in mitochondrial cytopathies: new ideas on
      pathogenesis and therapeutic targets.
AB  - Mitochondrial cytopathies are a heterogeneous group of human disorders triggered
      by disturbed mitochondrial function. This can be due to primary mitochondrial DNA
      mutations or nuclear defects affecting key components of the mitochondrial
      machinery. Optic neuropathy is a frequent disease manifestation and the degree of
      visual failure can be profound, with a severe impact on the patient's quality of
      life. This review focuses on the major mitochondrial disorders exhibiting optic
      nerve involvement, either as the defining clinical feature or as an additional
      component of a more extensive phenotype. Over the past decade, significant
      progress has been achieved in our basic understanding of Leber hereditary optic
      neuropathy and autosomal-dominant optic atrophy--the two classical paradigms for
      these mitochondrial optic neuropathies. There are currently limited treatments
      for these blinding ocular disorders and, ultimately, the aim is to translate
      these major advances into tangible benefits for patients and their families.

PMID- 22392507
TI  - Blood glutamate scavengers prolong the survival of rats and mice with brain
      implanted gliomas.
AB  - L-Glutamate (Glu) plays a crucial role in the growth of malignant gliomas. We
      have established the feasibility of accelerating a naturally occurring brain to
      blood Glu efflux by decreasing blood Glu levels with intravenous oxaloacetate,
      the respective Glu co-substrate of the blood resident enzyme humane glutamate
      oxaloacetate transaminase(hGOT). We wished to demonstrate that blood Glu
      scavenging provides neuroprotection in the case of glioma.We now describe the
      neuroprotective effects of blood Glu scavenging in a fatal condition such as
      brain-implanted C6 glioma in rats and brain-implanted human U87 MG glioma in nude
      mice. Rat (C-6) or human (U87) glioma cells were grafted stereotactically in the
      brain of rats or mice. After development of tumors, the animals were drinking
      oxaloacetate with or without injections of hGOT. In addition, mice were treated
      with combination treatment, which included drinking oxaloacetate with
      intracutaneous injections of hGOT and intraperitoneal injection of Temozolomide.
      Animals drinking oxaloacetate with or without injections of hGOT displayed a
      smaller tumor volume, reduced invasiveness and prolonged survival than control
      animals drinking saline. These effects were significantly enhanced by
      Temozolomide in mice, which increased survival by 237%. This is the first
      demonstration of blood Glu scavenging in brain cancer, and because of its safety,
      is likely to be of clinical significance for the future treatment of human
      gliomas. As we demonstrated, the blood glutamate scavenging treatment in
      combination with TMZ could be a good candidate or as an alternative treatment to
      the patients that do not respond to TMZ.

PMID- 22392509
TI  - Idiopathic pyoderma gangrenosum: successful resolution with infliximab therapy
      and pro-inflammatory cytokines assessment.

PMID- 22392508
TI  - Phase I trial of dasatinib and ixabepilone in patients with solid tumors.
AB  - PURPOSE: Dasatinib is an oral tyrosine kinase inhibitor (TKI) of BCR-ABL and SRC
      family and ixabepilone is an epothilone B analog. Synergistic activity has been
      reported when combining dasatinib with chemotherapy. This study was conducted to
      determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses
      (MTDs) for this combination. PATIENTS AND METHODS: Patients with metastatic solid
      tumors who progressed on standard therapy received dasatinib orally daily and
      ixabepilone IV every 3 weeks at escalating doses using 3 + 3 design. An expansion
      cohort was studied after reaching the MTD. Pharmacokinetic studies were
      performed. RESULTS: Nineteen patients were enrolled. No DLTs were observed at
      dose level (DL) 1 (dasatinib 100 mg and ixabepilone 30 mg/m(2)). At DL 2
      (dasatinib 100 mg and ixabepilone 40 mg/m(2)), one patient had multiple DLTs. At
      DL 3 (dasatinib 150 mg and ixabepilone 40 mg/m(2)), the first patient developed
      grade 3 AE during cycle 2, the second patient had a DLT and a grade 3 AE during
      cycle 2. The accrual to DL 3 was halted without reaching the maximally
      administered dose (MAD) and MTDs were determined to be dasatinib 100 mg and
      ixabepilone 40 mg/m(2) (DL 2). One patient had a partial response and 12 patients
      stable disease as their best response. Fourteen patients came off study due to
      toxicities. CONCLUSION: The combination of dasatinib and ixabepilone showed
      modest clinical activity with doses 100 mg orally daily and 40 mg/m(2) IV every 3
      weeks, respectively. Treatment related toxicities were seen frequently.

PMID- 22392510
TI  - Halogen anion-induced formation of[(PdLX)2] (X = Cl-, Br-, I-) vs. [PdL2] (L = [6
      MeO(O)CC6H4NHC(S)NP(S)(OiPr)2]-): reversible photoinduced cis/trans isomerization
      of [PdL2].
AB  - Reaction of the potassium salt of N-thiophosphorylated thiourea 6
      MeO(O)CC(6)H(4)NHC(S)NHP(S)(OiPr)(2) (HL) with PdX(2) (X = Cl(-), Br(-), I(-))
      leads to the dark red binuclear complexes [(PdLX)(2)], while the same reaction
      with PdY(2) (Y = NO(3)(-), CN(-), CH(3)COO(-)) leads to the light red mononuclear
      complex [PdL(2)]. [PdL(2)] exhibits reversible photoinduced cis-isomerization
      upon irradiation at 365 or 450 nm, reverting back to the trans-isomer in darkness
      or upon irradiation at 546 nm.

PMID- 22392512
TI  - Zn(II) and Cd(II) coordination polymers assembled by di(1H-imidazol-1-yl)methane
      and carboxylic acid ligands.
AB  - Five new Zn(II)/Cd(II) coordination polymers constructed from di(1H-imidazol-1
      yl)methane (L) mixed with different auxiliary carboxylic acid ligands formulated
      as [Zn(L)(H(2)L(1))(2).(H(2)O)(0.2)](n) (1), {[Zn(L)(L(2))].H(2)O}(n) (2),
      {[Cd(2)(L)(2)(L(2))(2)].2H(2)O}(n) (3), {[Cd(L)(L(3))].H(2)O}(n) (4) and
      [Cd(L)(L(4))](n) (5) (H(3)L(1) = 1,3,5-benzenetricarboxylic acid, H(2)L(2) = 4,4'
      oxybis(benzoic acid), H(2)L(3) = m-phthalic acid and H(2)L(4) = p-phthalic acid)
      have been synthesized under hydrothermal conditions and structurally
      characterized. Four related auxiliary carboxylic acids were chosen to examine the
      influences on the construction of these coordination frameworks with distinct
      dimensionality and connectivity. The coordination arrays of 1-5 vary from 1D
      zigzag chain for 1, 2D (4,4) layer for 2-4, to 2-fold interpenetrated 3D
      coordination network with the alpha-Po topology for 5. The thermal and
      photoluminescence properties of complexes 1-5 in the solid state have also been
      investigated.

PMID- 22392513
TI  - Analysis of in vitro oxidized human LDL phospholipids by solid-phase extraction
      and micellar electrokinetic capillary chromatography.
AB  - Phospholipids of in vitro oxidized human low-density lipoproteins (LDL) were
      separated by two different solid-phase extraction (SPE) methods. One of the two
      methods was designed to test the effects of gradient elution. This SPE method
      isolated more phospholipids from in vitro oxidized LDL than the other one
      according to the results of liquid chromatography and electrospray ionization
      mass spectrometry (LC ESI-MS) analysis. A micellar electrokinetic capillary
      chromatography (MEKC) method was also used to analyze phospholipids separated by
      SPE. The results of MEKC and LC ESI-MS were consistent for the major phospholipid
      classes, including PC, lysoPC, PE, PI and PS. The MEKC profiles showed
      significant differences for native and oxidized LDL phospholipids. Therefore, the
      unique combination of SPE and MEKC methods showed dramatic distinctions between
      native and in vitro oxidized human LDL phospholipids. The combination also shows
      great potential for rapid analysis of in vivo oxidized human LDL phospholipids in
      the future.

PMID- 22392514
TI  - Development and validation of a HPAE-PAD method for the quantification of
      CGP69669A, a sialyl Lewis(x)  mimetic, in skin permeation studies.
AB  - A simple, rapid, precise and specific isocratic HPAE-PAD method for
      quantification of CGP69669A was developed and validated. CGP69669A is a
      glycomimetic of sialyl Lewis(x) and an antagonist of E-selectin with potential
      application in the treatment of inflammatory skin disease. Quantification was
      performed using a Dionex CarboPac(TM) PA-200 anion-exchange column (3 * 250 mm)
      with 100 mm NaOH solution as mobile phase, a flow rate of 0.50 mL/min and an
      injection volume of 10 MUL. A quadruple potential waveform was used to detect the
      carbohydrate (+0.1 V from 0.00 to 0.40 s, -2.0 V from 0.41 to 0.42 s, +0.6 V at
      0.43 s and -0.1 V from 0.44 to 0.50 s with current integrated between 0.20 and
      0.40 s for detection) and rafinose was employed as an internal standard. The
      optimized conditions enabled rapid elution of CGP69669A (at 3.0 min) without
      interference from solvent peaks or substances present in the skin. The method
      showed good intra- and inter-day precision and accuracy and the response was
      linear from 1.0 to 25 ug/mL. This is the first validated direct method for the
      quantification of CGP69669A. It will now be employed in studies investigating the
      topical and transdermal delivery of CGP69669A in vitro and in vivo and it should
      also be of use for other applications of this molecule.

PMID- 22392515
TI  - Quantitative determination of uridine in rabbit plasma and urine by liquid
      chromatography coupled to a tandem mass spectrometry.
AB  - Recently a pyrimidine nucleoside, uridine, has been show to have a protective
      effect on cultured human corneal epithelial cells, and on dry eye animal model
      and patients. In this study, we introduce a sensitive liquid
      chromatography/tandem mass spectrometry method for the determination of uridine
      in rabbit plasma and urine. After protein precipitation with methanol including
      methaqualone (internal standard), the analyte was chromatographed on a reversed
      phase column with a mobile phase of 0.1% formic acid aqueous solution and
      methanol (1:4, v/v). The accuracy and precision of the assay were in accordance
      with Food and Drug Administration regulations for the validation of bioanalytical
      methods. This method was used to measure the concentrations of uridine in plasma
      and urine after a single oral administration of 450 mg/kg uridine in rabbits.

PMID- 22392516
TI  - Online sex-seeking, substance use, and risky behaviors in Taiwan: results from
      the 2010 Asia Internet MSM Sex Survey.
AB  - We conducted an online behavioral survey to estimate the prevalence of online sex
      seeking and substance use behaviors and to compare risky behaviors among men
      using different venues to seek sex with men. A cross-sectional online survey, the
      Asia Internet MSM Sex Survey, was conducted online from January 1 to February 28,
      2010. Of the 1,645 participants enrolled from Taiwan, 72.4% reported the Internet
      as the main way of seeking sexual partners, 73.9% had had sex with partners found
      online, and 16% had used recreational drugs in the previous 6 months. There was
      no evidence to suggest that men who looked for sex through the Internet were more
      likely to engage in unprotected anal intercourse with their casual partners than
      those using other gay venues. Having had online sex partners in the previous 6
      months was significantly associated with being young [adjusted odd ratio (AOR) =
      0.97, 95% CI: 0.95-0.99], having had no steady partners in the previous year (AOR
      = 0.24, 95% CI: 0.15-0.39), having had more than five partners in the previous 6
      months (AOR = 4.57, 95% CI: 2.95-7.11), having used recreational drugs in the
      previous 6 months (AOR = 2.24, 95% CI: 1.30-3.87), and having had an STI in the
      previous 6 months (AOR = 4.24, 95% CI: 1.59-11.30). In conclusion, because the
      Internet is a popular meeting place for MSM in Taiwan, effective and targeted
      prevention programs should be developed to minimize the HIV transmission risk in
      the Internet era.

PMID- 22392517
TI  - Feederism: an exaggeration of a normative mate selection preference?
AB  - Quinsey and Lalumiere (1995) suggested that some, if not most, paraphilias are
      exaggerated manifestations of more normative and functional mate selection
      preferences. The present study tested whether Feederism, a fat fetish focused on
      erotic eating, feeding, and gaining weight, is an exaggeration of a sexual
      arousal pattern commonly seen in the general population. Thirty participants (15
      men and 15 women) recruited from the general population were assessed using
      penile plethysmography and vaginal photoplethysmography, respectively. None of
      the participants were self-identified Feeders or Feedees. Participants were shown
      sexual, neutral, and feeding still images while listening to audio recordings of
      sexual, neutral, and feeding stories. Participants did not genitally respond to
      feeding stimuli. However, both men and women subjectively rated feeding stimuli
      as more sexually arousing than neutral stimuli. We discuss the discordance
      between physiological and self-reported sexual arousal in the context of sex
      differences in sexual concordance and implications for future research.

PMID- 22392518
TI  - Charge transport in fibre-based perylene-diimide transistors: effect of the alkyl
      substitution and processing technique.
AB  - We report a comparative study on the self-assembly from solution and electrical
      characterization of n-type semiconducting fibres obtained from five different
      perylenebis(dicarboximide) (PDI) derivatives. In particular we investigated the
      role of the nature of the alkyl chain covalently linked to the N,N' sites of the
      PDI in modulating the molecular solubility and aggregation capacity. We explored
      the morphologies of the self-assembled architectures physisorbed on dielectric
      surfaces and in particular how they can be modified by tuning the deposition and
      post-deposition procedures, i.e. by modulating the kinetics of the self-assembly
      process. To this end, alongside the conventional spin-coating, solvent vapour
      annealing (SVA) and solvent induced precipitation (SIP) have been employed. Both
      approaches led to fibres having widths of several hundred nanometres and lengths
      up to tens of micrometres. SVA formed isolated fibres which were tens of
      nanometres high, flat, and tapered at the ends. Conversely, SIP fibres exhibited
      nearly matching heights and widths, but organized into bundles. Despite these
      morphological differences, the same intermolecular packing is found by XRD in
      each type of structure, albeit with differing degrees of long-range order. The
      study of the electrical characteristics of the obtained low dimensional nano
      assemblies has been accomplished by fabricating and characterizing organic field
      effect transistors.

PMID- 22392519
TI  - Development and (pre-) clinical assessment of a novel surgical tool for primary
      and secondary tracheoesophageal puncture with immediate voice prosthesis
      insertion, the Provox Vega Puncture Set.
AB  - Development and (pre-) clinical assessment were performed of a novel surgical
      tool for primary and secondary tracheoesophageal puncture (TEP) with immediate
      voice prosthesis (VP) insertion in laryngectomized patients, the Provox Vega
      Puncture Set (PVPS). After preclinical assessment in fresh frozen cadavers, a
      multicenter prospective clinical feasibility study in two stages was performed.
      Stage-1 included 20 patients, and stage-2 had 27. Based on observations in stage
      1, the PVPS was re-designed (decrease in diameter of the dilator from 23.5 to 18
      Fr.) and further used in stage-2. Primary outcome measure was immediate VP
      insertion without requiring additional instruments. Secondary outcome measures
      for comparison of the new with the traditional TEP procedure were: appreciation,
      ease of use, time consumption, estimated surgical risks and overall preference. A
      mini-max two-stage study design was used to establish the required sample size.
      In stage-1, dilatation forces were considered too high in patients with a
      fibrotic TE wall. With the final thinner version of the PVPS, VPs were
      successfully inserted into the TEP in 'one-go' in 24/27 (89%) of TEPs: 20 primary
      and 7 secondary. Participating surgeons rated appreciation, ease of use, time
      consumption and estimated surgical risks as better. Related adverse events were
      few and minor. The new PVPS appeared to be the preferred device by all
      participating surgeons. This study shows that the novel, disposable PVPS is a
      useful TEP instrument allowing quick and easy insertion of the VP in the vast
      majority of cases without requiring additional instruments.

PMID- 22392520
TI  - Long-term outcomes of endonasal surgery for choanal atresia: 28 years experience
      in an academic medical centre.
AB  - This study aimed to evaluate the long-term outcomes of endonasal surgical
      treatment for choanal atresia (CA) and determine possible predictors of
      recurrence. A retrospective study of 50 cases of CA that were managed endonasally
      was conducted at an academic tertiary referral centre. Recurrence of disease was
      assessed with regard to the type and nature of atresia, presence of CHARGE
      association and stent usage. Bilateral CA cases (n = 76 sides) were operated at
      an early age and had an incidence of recurrence of 57%, while unilateral cases
      had a recurrence rate of 25% (3/12). Use of stents did not have a statistically
      significant effect on the rate of recurrence. However, a significantly higher
      recurrence rate was noted in patients with purely bony atretic plates (p < 0.001)
      or CHARGE association (p = 0.049). A tendency towards a higher recurrence rate in
      bilateral atresias was also found (p = 0.085). The transnasal approach is a safe
      and effective way to re-establish the nasal choanae. However, appropriate
      information on the likelihood of recurrence should be included in the
      preoperative counselling of patients and their parents, especially in cases with
      bilateral atresia or CHARGE association.

PMID- 22392521
TI  - Re: Thyroid incidentalomas in FDG-PET/CT: prevalence and clinical impact.

PMID- 22392522
TI  - Factors influencing self- and parent-reporting health-related quality of life in
      children with brain tumors.
AB  - PURPOSE: Health-related quality of life (HRQOL) is not only a degree of health
      but also reflects patient perceptions and expectations of health. For children
      with brain tumors, better understanding of HRQOL requires the use of
      complementary reports from parents and interviewer-administered reports for
      children. Here, we aimed to test whether or not the trait anxiety of children and
      the psychological distress of their parents influence children's and parents'
      responses to HRQOL questionnaires, and whether or not the report-administration
      method for children influences children's responses to HRQOL questionnaires.
      METHODS: One hundred and thirty-four children aged 5-18 with brain tumors and one
      of their parents completed the Pediatric Quality of Life Inventory(TM)
      (PedsQL(TM)) Brain Tumor Module questionnaires. In addition, the children also
      completed the State-Trait Anxiety Inventory for Children (STAIC), and the parents
      also completed the Kessler-10 (K10) and health and sociodemographic
      characteristics questionnaires. The child questionnaires were administered either
      by the child (self-administered) or an interviewer. Rater-dependent perceptions
      about HRQOL were derived from the subscales scores of the PedsQL(TM) Brain Tumor
      Module using structural equation modeling based on a multitrait-multimethod
      model. The STAIC trait-anxiety score, K10 score, report-administration method,
      and other health and sociodemographic factors related to each child's or parent's
      perceptions were identified through multiple linear regression analyses of the
      questionnaire responses. We used a path analysis to estimate the change in a
      PedsQL(TM) child-reported score that occurs when interviewer-administration
      changes the child's perception about HRQOL. RESULTS: Surveys for 89 children were
      self-administered while those for 45 were interviewer-administered. The
      perceptions of the children and parents were calculated by fitting data to the
      model (chi-squared P = 0.087, normed fit index = 0.932, comparative fit index =
      0.978, standardized root mean squared residual = 0.053, and root mean square
      error of approximation = 0.054). The children's perception of HRQOL was affected
      by their STAIC trait-anxiety score (b = -0.43, 95% CI [-0.60, -0.25]). The
      parent's perception was affected by their child's treatment status (b = 0.26, 95%
      CI [0.09, 0.43]), the parent's K10 score (b = -0.21, 95% CI [-0.37, -0.04]), and
      by education level (b = 0.17, 95% CI [0.00, 0.34]). The change in the child
      reported PedsQL(TM) score in relation to the method of administration ranged from
      -1.1 (95% CI: -3.5, 1.3) on the procedural anxiety subscale to -2.5 (95% CI: 
      7.6, 2.6) on the movement and balance subscale. CONCLUSION: Child-reporting of
      HRQOL is little influenced by the method of administration. Children's perception
      about HRQOL tended to be influenced by their trait anxiety, while parents'
      perception was influenced by their psychological distress, academic background,
      and their child's treatment status.

PMID- 22392524
TI  - Feasibility, reliability and validity of the Chinese simplified version of the
      MOS-HIV health survey among AIDS patients in China.
AB  - PURPOSES: To test the feasibility, reliability and validity of the Chinese
      simplified version of the MOS-HIV health survey among AIDS patients in China.
      METHODS: A cross-sectional survey of 120 patients receiving highly active
      antiretroviral treatment was conducted. Feasibility was assessed using the time
      of administration and the response rate. Reliability was estimated using
      Cronbach's alpha. Validity was analyzed by construct and discriminant validity.
      RESULTS: The time of administration was about 12 min, and the response rate was
      100%. The MOS-HIV showed a good internal reliability and Cronbach's alpha of
      eight multi-item scales ranged from 0.75 to 0.91. Correlations between scales
      were all significant. The majority of the correlations between pairs of scales
      were within the acceptable range (0.4-0.8). The scores of role function, pain,
      physical health summary scales were significantly higher for patients with time
      on antiretroviral treatment >1 year compared to those with time <= 1 year.
      Patients >40 years had significantly higher scores than those of <= 40 years on
      energy and mental health summary scales. CONCLUSIONS: The Chinese simplified
      version of MOS-HIV health survey had good feasibility, reliability and validity.
      It was successfully adapted for AIDS patients in rural areas and could be a
      valuable tool in evaluating the quality of life of AIDS patients.

PMID- 22392523
TI  - Estimating utilities for chronic kidney disease, using SF-36 and SF-12-based
      measures: challenges in a population of veterans with diabetes.
AB  - PURPOSE: Using transformations of existing quality-of-life data to estimate
      utilities has the potential to efficiently provide investigators with utility
      information. We used within-method and across-method comparisons and estimated
      disutilities associated with increasing chronic kidney disease (CKD) severity.
      METHODS: In an observational cohort of veterans with diabetes (DM) and pre
      existing SF-36/SF-12 responses, we used six transformation methods (SF-12 to EQ
      5D, SF-36 to HUI2, SF-12 to SF-6D, SF-36 to SF-6D, SF-36 to SF-6D (Bayesian
      method), and SF-12 to VR-6D) to estimate unadjusted utilities. CKD severity was
      staged using glomerular filtration rate estimated from serum creatinines, with
      the modification of diet in renal disease formula. We then used multivariate
      regression to estimate disutilities specifically associated with CKD severity
      stage. RESULTS: Of 67,963 patients, 22,273 patients had recent-onset DM and
      45,690 patients had prevalent DM. For the recent-onset group, the adjusted
      disutility associated with CKD derived from the six transformation methods ranged
      from 0.0029 to 0.0045 for stage 2; -0.004 to -0.0009 for early stage 3; -0.017 to
      -0.010 for late stage 3; -0.023 to -0.012 for stage 4; -0.078 to -0.033 for stage
      5; and -0.012 to -0.001 for ESRD/dialysis. CONCLUSION: Disutility did not
      increase monotonically as CKD severity increased. Differences in disutilities
      estimated using the six different methods were found. Both findings have
      implications for using such estimates in economic analyses.

PMID- 22392525
TI  - Burkitt post-transplantation lymphoma in adult solid organ transplant recipients:
      sequential immunochemotherapy with rituximab (R) followed by cyclophosphamide,
      doxorubicin, vincristine, and prednisone (CHOP) or R-CHOP is safe and effective
      in an analysis of 8 patients.
AB  - BACKGROUND: Burkitt lymphoma post-transplantation lymphoproliferative disorder
      (Burkitt-PTLD) is a rare form of monomorphic B-cell PTLD for which no standard
      treatment has been established. Currently, the treatment of Burkitt lymphoma
      outside the post-transplantation setting involves high doses of alkylating
      agents, frequent dosing, and intrathecal and/or systemic central nervous system
      prophylaxis. In PTLD, however, such protocols are associated with considerable
      toxicity and mortality. METHODS: The authors present a retrospective series of 8
      adult patients with Burkitt-PTLD. Six patients were reported to the prospective
      German PTLD registry or were enrolled in the PTLD-1 trial, and 2 patients had
      received treatment before 2000, thus allowing for comparison with the pre
      rituximab era. RESULTS: Seven of the 8 patients were men. The median age at
      presentation was 38 years, and the median time since transplantation was 5.7
      years. Five of 8 patients had histologically established, Epstein-Barr virus
      associated disease, and 7 of 7 patients were positive for a MYC translocation.
      Five of 8 patients received sequential immunochemotherapy (4 courses of rituximab
      [R] followed by 4 cycles of cyclophosphamide, doxorubicin, vincristine, and
      prednisolone [CHOP] or R plus CHOP [R-CHOP]). In this group, 5 of 5 patients
      reached complete remission (CR), and their overall survival (OS) was
      significantly longer (P = .008) compared with the OS for 2 of 8 patients who
      received first-line CHOP and did not respond. One of 8 patients (who had stage IV
      disease with meningiosis) received combination therapy (cyclophosphamide
      pretreatment, rituximab, intrathecal chemotherapy, whole-brain irradiation, and
      radioimmunotherapy) and reached CR. Overall, 6 of 8 patients reached CR; and,
      after a median follow-up of 4.7 years (range, 1.7-4.8 years), the median OS was
      36.7 months. There was no treatment-related mortality under first-line therapy.
      CONCLUSIONS: In the largest adult case series in Burkitt-PTLD to date, sequential
      immunochemotherapy with rituximab followed by standard CHOP or R-CHOP was a both
      safe and effective treatment.

PMID- 22392526
TI  - Changes in parameters of bone metabolism in postmenopausal women following a 12
      month intervention period using dairy products enriched with calcium, vitamin D,
      and phylloquinone (vitamin K(1)) or menaquinone-7 (vitamin K (2)): the
      Postmenopausal Health Study II.
AB  - The objective of the present study was to examine the effect of dairy products
      enriched with calcium, vitamin D(3), and phylloquinone (vitamin K(1)) or
      menaquinone-7 (vitamin K(2)) on parameters of bone metabolism in postmenopausal
      women following a 12-month intervention. Postmenopausal women were divided into
      three intervention groups and a control group (CG). All three intervention groups
      attended biweekly sessions and received fortified dairy products providing daily
      800 mg of calcium and 10 MUg of vitamin D(3) (CaD). Furthermore, in two of the
      three intervention groups the dairy products were also enriched with vitamin K,
      providing daily 100 MUg of either phylloquinone (CaDK1) or menaquinone-7 (CaDK2).
      The increase observed for serum 25(OH)D levels in all intervention groups and the
      increase observed for serum IGF-I levels in the CaDK2 group differed
      significantly compared to the changes observed in CG (P = 0.010 and P = 0.028,
      respectively). Furthermore, both the CaDK1 and CaDK2 groups had a significantly
      lower mean serum undercarboxylated osteocalcin to osteocalcin ratio and urine
      deoxypyridinoline levels at follow-up compared to the CaD and CG groups (P =
      0.001 and P = 0.047, respectively). Significant increases in total-body BMD were
      observed in all intervention groups compared to CG (P < 0.05), while significant
      increases in lumbar spine BMD were observed only for CaDK1 and CaDK2 compared to
      CG (P < 0.05) after controlling for changes in serum 25(OH)D levels and dietary
      calcium intake. In conclusion, the present study revealed more favorable changes
      in bone metabolism and bone mass indices for the two vitamin K-supplemented
      groups, mainly reflected in the suppression of serum levels of bone remodeling
      indices and in the more positive changes in lumbar spine BMD for these two study
      groups.

PMID- 22392527
TI  - 17beta-estradiol rapidly activates calcium release from intracellular stores via
      the GPR30 pathway and MAPK phosphorylation in osteocyte-like MLO-Y4 cells.
AB  - Estrogen regulates critical cellular functions, and its deficiency initiates bone
      turnover and the development of bone mass loss in menopausal females. Recent
      studies have demonstrated that 17beta-estradiol (E(2)) induces rapid non-genomic
      responses that activate downstream signaling molecules, thus providing a new
      perspective to understand the relationship between estrogen and bone metabolism.
      In this study, we investigated rapid estrogen responses, including calcium
      release and MAPK phosphorylation, in osteocyte-like MLO-Y4 cells. E(2) elevated
      [Ca(2+)]( i ) and increased Ca(2+) oscillation frequency in a dose-dependent
      manner. Immunolabeling confirmed the expression of three estrogen receptors
      (ERalpha, ERbeta, and G protein-coupled receptor 30 [GPR30]) in MLO-Y4 cells and
      localized GPR30 predominantly to the plasma membrane. E(2) mobilized calcium from
      intracellular stores, and the use of selective agonist(s) for each ER showed that
      this was mediated mainly through the GPR30 pathway. MAPK phosphorylation
      increased in a biphasic manner, with peaks occurring after 7 and 60 min. GPR30
      and classical ERs showed different temporal effects on MAPK phosphorylation and
      contributed to MAPK phosphorylation sequentially. ICI182,780 inhibited E(2)
      activation of MAPK at 7 min, while the GPR30 agonist G-1 and antagonist G-15
      failed to affect MAPK phosphorylation levels. G-1-mediated MAPK phosphorylation
      at 60 min was prevented by prior depletion of calcium stores. Our data suggest
      that E(2) induces the non-genomic responses Ca(2+) release and MAPK
      phosphorylation to regulate osteocyte function and indicate that multiple
      receptors mediate rapid E(2) responses.

PMID- 22392528
TI  - Improved diffusion imaging through SNR-enhancing joint reconstruction.
AB  - Quantitative diffusion imaging is a powerful technique for the characterization
      of complex tissue microarchitecture. However, long acquisition times and limited
      signal-to-noise ratio represent significant hurdles for many in vivo
      applications. This article presents a new approach to reduce noise while largely
      maintaining resolution in diffusion weighted images, using a statistical
      reconstruction method that takes advantage of the high level of structural
      correlation observed in typical datasets. Compared to existing denoising methods,
      the proposed method performs reconstruction directly from the measured complex k
      space data, allowing for gaussian noise modeling and theoretical
      characterizations of the resolution and signal-to-noise ratio of the
      reconstructed images. In addition, the proposed method is compatible with many
      different models of the diffusion signal (e.g., diffusion tensor modeling and q
      space modeling). The joint reconstruction method can provide significant
      improvements in signal-to-noise ratio relative to conventional reconstruction
      techniques, with a relatively minor corresponding loss in image resolution.
      Results are shown in the context of diffusion spectrum imaging tractography and
      diffusion tensor imaging, illustrating the potential of this signal-to-noise
      ratio-enhancing joint reconstruction approach for a range of different diffusion
      imaging experiments.

PMID- 22392529
TI  - Decision making in advanced heart failure: a scientific statement from the
      American Heart Association.

PMID- 22392530
TI  - Role for substance p-based nociceptive signaling in progenitor cell activation
      and angiogenesis during ischemia in mice and in human subjects.
AB  - BACKGROUND: Pain triggers a homeostatic alarm reaction to injury. It remains
      unknown, however, whether nociceptive signaling activated by ischemia is relevant
      for progenitor cells (PC) release from bone marrow. To this end, we investigated
      the role of the neuropeptide substance P (SP) and cognate neurokinin 1 (NK1)
      nociceptor in PC activation and angiogenesis during ischemia in mice and in human
      subjects. METHODS AND RESULTS: The mouse bone marrow contains sensory fibers and
      PC that express SP. Moreover, SP-induced migration provides enrichment for PC
      that express NK1 and promote reparative angiogenesis after transplantation in a
      mouse model of limb ischemia. Acute myocardial infarction and limb ischemia
      increase SP levels in peripheral blood, decrease SP levels in bone marrow, and
      stimulate the mobilization of NK1-expressing PC, with these effects being
      abrogated by systemic administration of the opioid receptor agonist morphine.
      Moreover, bone marrow reconstitution with NK1-knockout cells results in depressed
      PC mobilization, delayed blood flow recovery, and reduced neovascularization
      after ischemia. We next asked whether SP is instrumental to PC mobilization and
      homing in patients with ischemia. Human PC express NK1, and SP-induced migration
      provides enrichment for proangiogenic PC. Patients with acute myocardial
      infarction show high circulating levels of SP and NK1-positive cells that
      coexpress PC antigens, such as CD34, KDR, and CXCR4. Moreover, NK1-expressing PC
      are abundant in infarcted hearts but not in hearts that developed an infarct
      after transplantation. CONCLUSIONS: Our data highlight the role of SP in
      reparative neovascularization. Nociceptive signaling may represent a novel target
      of regenerative medicine.

PMID- 22392531
TI  - Spinal cord injury pain: mechanisms and management.
AB  - Patients with spinal cord injury (SCI) may experience several types of chronic
      pain, including peripheral and central neuropathic pain, pain secondary to
      overuse, painful muscle spasms, and visceral pain. An accurate classification of
      the patient's pain is important for choosing the optimal treatment strategy. In
      particular, neuropathic pain appears to be persistent despite various treatment
      attempts. In recent years, we have gained increasing knowledge of SCI pain
      mechanisms from experimental models and clinical studies. Nevertheless, treatment
      remains difficult and inadequate. In line with the recommendations for peripheral
      neuropathic pain, evidence from randomized controlled treatment trials suggests
      that tricyclic antidepressants and pregabalin are first-line treatments. This
      review highlights the diagnosis and classification of SCI pain and recent
      improvements in the understanding of underlying mechanisms, and provides an
      update on treatment of SCI pain.

PMID- 22392532
TI  - Diabetic macular edema: therapeutic options.
AB  - Treatment for diabetic macular edema (DME) is continuously evolving with the
      advent of pharmacologic therapies. Focal laser photocoagulation remains the
      historical standard of care; however, a new wave of studies is rapidly emerging
      that shows the benefit of intravitreal antivascular endothelial growth factor
      medications and corticosteroids. The goal of this review is to compare the
      various treatment options for DME, and include data from the most recent clinical
      trials of therapies for this complex condition.

PMID- 22392534
TI  - Chemo-switched chromatic, magnetic and structural changes with retention of
      molecular crystallinity, Ni(12aneS4)(BF4)2.
AB  - The molecular crystal [Ni(12aneS(4))](BF(4))(2) (12aneS(4) = 1,4,7,10
      tetrathiacyclododecane) displays the uncommon ability to retain its crystallinity
      on facile reversible hydration/dehydration without requiring polymeric bonding
      and despite the significant structural changes required. The flexibility of the
      12aneS(4) ring facilitates rearrangement of the complex in the solid state upon
      absorption of two equivalents of water, with the crystal structures showing a
      clear topotactic relationship. The well defined chromatic, structural and
      magnetic changes that are both highly sensitive and easily reversed makes this
      complex of interest as an environmentally responsive material and as a
      contrasting example to the commonly reported coordination polymers.

PMID- 22392535
TI  - Translation through argumentation in medical research and physician-citizenship.
AB  - While many "benchtop-to-bedside" research pathways have been developed in "Type
      I" translational medicine, vehicles to facilitate "Type II" and "Type III"
      translation that convert scientific data into clinical and community
      interventions designed to improve the health of human populations remain elusive.
      Further, while a high percentage of physicians endorse the principle of citizen
      leadership, many have difficulty practicing it. This discrepancy has been
      attributed, in part, to lack of training and preparation for public advocacy,
      time limitation, and institutional resistance. As translational medicine and
      physician-citizenship implicate social, political, economic and cultural factors,
      both enterprises require "integrative" research strategies that blend insights
      from multiple fields of study, as well as rhetorical acumen in adapting messages
      to reach multiple audiences. This article considers how argumentation theory's
      epistemological flexibility, audience attentiveness, and heuristic qualities,
      combined with concepts from classical rhetoric, such as rhetorical invention, the
      synecdoche, and ethos, yield tools to facilitate translational medicine and
      enable physician-citizenship.

PMID- 22392536
TI  - 'Misery loves company': sexual trauma, psychoanalysis and the market for misery.
AB  - This article examines sexual 'misery memoirs', focusing on author/reader and
      genre/market relationships in the context of models of trauma and child sexual
      abuse. It shows that the success of sexual 'misery memoirs' is inextricably bound
      up with the popular dissemination of a feminist-psychoanalytic model of traumatic
      memory that has taken place since the 1970s. It also argues that, as the 'truth'
      of recovered and traumatic memories has been fundamental to its success,
      anxieties about false memory and hoax 'misery memoirs' have posed a challenge to
      the genre and established a market for 'retractor' narratives.

PMID- 22392533
TI  - Osteoarthritis: a disease of the joint as an organ.

PMID- 22392537
TI  - Birth: a collection of poems.

PMID- 22392538
TI  - Does osteoporosis therapy invalidate FRAX for fracture prediction?
AB  - Ten-year fracture risk assessment with the fracture risk assessment system (FRAX)
      is increasingly used to guide treatment decisions. Osteoporosis pharmacotherapy
      reduces fracture risk, but the effect is greater than can be explained from the
      increase in bone mineral density (BMD). Whether this invalidates fracture
      predictions with FRAX is uncertain. A total of 35,764 women (age >=50 years) and
      baseline BMD testing (1996-2007) had FRAX probabilities retroactively calculated.
      A provincial pharmacy database was used to identify osteoporosis medication use.
      Women were categorized as untreated, current high adherence users [medication
      possession ratio (MPR) >=0.80 in the year after BMD testing], current low
      adherence users (MPR <0.80), and past users. Fractures outcomes to 10 years were
      established form a population-based health data repository. FRAX and femoral neck
      BMD alone stratified major osteoporotic and hip fracture risk within untreated
      and each treated subgroup (all p-values <0.001) with similar area under the
      receiver operating characteristic curve. In untreated and each treated subgroup,
      a stepwise gradient in observed 10-year major osteoporotic and hip fracture
      incidence was found as a function of the predicted probability tertile (all p
      values <0.001 for linear trend). Concordance (calibration) plots for major
      osteoporotic fractures and hip fractures showed good agreement between the
      predicted and observed 10-year fracture incidence in untreated women and each
      treated subgroup. Only in the highest risk tertile of women highly adherent to at
      least 5 years of bisphosphonate use was observed hip fracture risk significantly
      less than predicted, though major osteoporotic fracture risk was similar to
      predicted. In summary, this work suggests that the FRAX tool can be used to
      predict fracture probability in women currently or previously treated for
      osteoporosis. Although FRAX should not be used to assess the reduction in
      fracture risk in individuals on treatment, it may still have value for guiding
      the need for continued treatment or treatment withdrawal

PMID- 22392539
TI  - CD99 is a novel prognostic stromal marker in non-small cell lung cancer.
AB  - The complex interaction between cancer cells and the microenvironment plays an
      essential role in all stages of tumourigenesis. Despite the significance of this
      interplay, alterations in protein composition underlying tumour-stroma
      interactions are largely unknown. The aim of this study was to identify stromal
      proteins with clinical relevance in non-small cell lung cancer (NSCLC). A list
      encompassing 203 stromal candidate genes was compiled based on gene expression
      array data and available literature. The protein expression of these genes in
      human NSCLC was screened using the Human Protein Atlas. Twelve proteins were
      selected that showed a differential stromal staining pattern (BGN, CD99, DCN,
      EMILIN1, FBN1, PDGFRB, PDLIM5, POSTN, SPARC, TAGLN, TNC and VCAN). The
      corresponding antibodies were applied on tissue microarrays, including 190 NSCLC
      samples, and stromal staining was correlated with clinical parameters. Higher
      stromal expression of CD99 was associated with better prognosis in the univariate
      (p = 0.037) and multivariate (p = 0.039) analysis. The association was
      independent from the proportion of tumour stroma, the fraction of inflammatory
      cells and clinical and pathological parameters like stage, performance status and
      tumour histology. The prognostic impact of stromal CD99 protein expression was
      confirmed in an independent cohort of 240 NSCLC patients (p = 0.008).
      Furthermore, double-staining confocal fluorescence microscopy showed that CD99
      was expressed in stromal lymphocytes as well as in cancer-associated fibroblasts.
      Based on a comprehensive screening strategy the membrane protein CD99 was
      identified as a novel stromal factor with clinical relevance. The results support
      the concept that stromal properties have an important impact on tumour
      progression.

PMID- 22392540
TI  - A comparative phylogenetic study of genetics and folk music.
AB  - Computer-aided comparison of folk music from different nations is one of the
      newest research areas. We were intrigued to have identified some important
      similarities between phylogenetic studies and modern folk music. First of all,
      both of them use similar concepts and representation tools such as
      multidimensional scaling for modelling relationship between populations. This
      gave us the idea to investigate whether these connections are merely accidental
      or if they mirror population migrations from the past. We raised the question;
      does the complex structure of musical connections display a clear picture and can
      this system be interpreted by the genetic analysis? This study is the first to
      systematically investigate the incidental genetic background of the folk music
      context between different populations. Paternal (42 populations) and maternal
      lineages (56 populations) were compared based on Fst genetic distances of the Y
      chromosomal and mtDNA haplogroup frequencies. To test this hypothesis, the
      corresponding musical cultures were also compared using an automatic overlap
      analysis of parallel melody styles for 31 Eurasian nations. We found that close
      musical relations of populations indicate close genetic distances (<0.05) with a
      probability of 82%. It was observed that there is a significant correlation
      between population genetics and folk music; maternal lineages have a more
      important role in folk music traditions than paternal lineages. Furthermore, the
      combination of these disciplines establishing a new interdisciplinary research
      field of "music-genetics" can be an efficient tool to get a more comprehensive
      picture on the complex behaviour of populations in prehistoric time.

PMID- 22392541
TI  - Pleural epithelioid hemangioendothelioma.

PMID- 22392543
TI  - Molecular design of chiral quaternary ammonium polymers for asymmetric catalysis
      applications.
AB  - Repeated reaction between a chiral quaternary ammonium dimer and disodium
      disulfonate gave a chiral ionic polymer, which showed excellent catalytic
      activity in the asymmetric benzylation of N-diphenylmethylene glycine tert-butyl
      ester.

PMID- 22392542
TI  - Reproductive success of three passerine species exposed to dioxin-like compounds
      near Midland, Michigan, USA.
AB  - Nests of three passerine birds, house wren (HOWR), tree swallow (TRES), and
      eastern bluebird (EABL) were monitored daily (2005-2007) at study areas (SAs)
      downstream of Midland, Michigan where soil and sediment concentrations of
      polychlorinated dibenzofurans (PCDFs) were significantly greater than the
      regional background concentrations and upstream reference areas (RAs). Similarly,
      TRES research conducted at sites contaminated with dioxin-like compounds
      indicated that concentrations of polychlorinated dibenzo-p-dioxins and PCDFs,
      expressed as SigmaPCDD/DFs and 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents
      observed in the diet and eggs of these three species would be predicted to cause
      significant effects on reproduction. However, site-specific reproductive
      parameters including hatching success and fledging success at downstream SAs were
      similar to or greater than those at upstream RAs. Specifically, hatching success
      was not significantly different among years, species, locations, or between early
      and late nesting attempts. Of all initiated clutches, 66% (n = 427), 73% (n =
      245), and 64% (n = 122) successfully fledged at least one nestling for HOWR,
      TRES, and EABL, respectively. Overall reproductive performance was similar
      between SAs and RAs. The reason for these unexpected results is consistent with
      the fact that there are species-specific and congener-specific differences in
      sensitivities to the effects of aryl hydrocarbon receptor agonists.

PMID- 22392544
TI  - Aggression, digit ratio, and variation in the androgen receptor, serotonin
      transporter, and dopamine D4 receptor genes in African foragers: the Hadza.
AB  - The role of genes in the expression of aggression and masculinity traits in
      humans has been a focus of recent behavioral genetic studies. This is the first
      study on the variation in aggression, the digit ratio (the ratio between the
      second and the fourth digits, 2D:4D), the directional asymmetry in 2D:4D (D(R-L))
      and polymorphisms of the AR, DRD4, and 5-HTTL genes in simple hunter-gatherers,
      namely the Hadza of Tanzania (142 adult men). The distribution of AR, DRD4E3, and
      5-HTTLPR genotypes and allele frequencies in Hadza was compared to other African
      populations on which the data were available. Hadza and Ariaal differed
      significantly in the distributions of frequencies of AR alleles with different
      numbers of CAG repeats. Hadza population was similar to other African populations
      in the distribution of allelic frequencies of the DRD4E3 locus, and to Afro
      Americans in the distribution of allelic types of the 5-HTTLPR locus. We found no
      influence of AR gene on the right hand 2D:4D ratio, D(R-L), and any of aggression
      subscales of the Buss-Perry Aggression Questionnaire (AQ). Although, a weak
      positive correlation between CAG repeats and the left hand 2D:4D was found. The
      multiple regression analysis with digit ratios, D(R-L) and aggression subscales
      of AQ as dependent variables and the three gene candidates (AR, DRD4E3, and 5
      HTTLPR) as independent variables revealed the following: men with lower number of
      CAG repeats had significantly lower left hand 2D:4D ratio; men with higher
      numbers of 48-bp unit copies in exon 3 of a VNTR polymorphism in the DRD4 gene
      had significantly lower digit ratios on both hands; no effect of the 5-HTTLPR
      gene on either the digit ratio or aggressive behavior. These findings demonstrate
      the complexity of gene effects on digit ratios and aggression and call for
      simultaneous analysis of more candidate genes. It is noteworthy that these
      results were obtained for a human population that is still practicing foraging
      and has been subjected to a high selective pressure due to harsh environments and
      practically has no access to modern medical care. Hadza are highly egalitarian,
      and their culture does not favor persons with a dominant or aggressive behavior.
      It is still to be found to what extent the relationships observed in this study
      are similar to those in other human populations.

PMID- 22392545
TI  - Erratum to: Osteoid osteoma and osteoblastoma of the spine: a review of the
      literature.

PMID- 22392546
TI  - Erratum to: Corticosteroid injection for tennis elbow or lateral epicondylitis: a
      review of the literature.

PMID- 22392547
TI  - Effect of dietary inclusion of fermented pigeon pea (Cajanus cajan) meal on
      growth, apparent nutrient digestibility and blood parameters of cockerel chicks.
AB  - The effect of dietary inclusion of fermented pigeon pea meal (FPPM) on growth
      response, apparent nutrient digestibility, haematological indices and serum
      biochemistry of cockerel chicks was studied using 240-day-old cockerel chicks
      allotted to four dietary treatments consisting of 60 birds each. Four
      experimental diets were formulated to include FPPM at 0, 50, 100 and 150 g/kg
      inclusion levels, respectively. Each of the diets was fed to 60 birds replicated
      six times with ten birds per replicate. The feeding trial lasted for 56 days.
      Results indicated that final live weight (linear (L). quadratic (Q): P < 0.05),
      weight gain (L.Q: P < 0.01), feed intake (Q.: P < 0.05) and coefficient of total
      tract apparent crude protein digestibility (P < 0.05) were reduced with
      increasing dietary inclusion of FPPM. Similar improved feed-to-gain ratios were
      obtained for chicks fed the control and those fed a diet containing 50 g/kg FPPM.
      Coefficient of total tract apparent ether extract and ash digestibility were not
      affected (P > 0.05) by the inclusion of FPPM. Haemoglobin and serum uric acid
      concentrations were also reduced (P < 0.05) with increasing dietary inclusion of
      FPPM. Chicks fed with 150 g/kg FPPM had the least (P < 0.05) packed cell volume,
      red blood cell and neutrophil count. It was concluded that dietary inclusion of
      up to 50 g/kg FPPM could be used in the ration for cockerel chicks without
      imposing any threat on the growth response, nutrient digestibility and blood
      constituents.

PMID- 22392548
TI  - Animal production systems of small farms in the Kaski district of Nepal.
AB  - The aim of this study was to describe animal production on small farms in the
      Kaski district of Nepal, with the goal of identifying areas where animal health
      and productivity could be improved. Eighty-five randomly selected farms from four
      different Village Development Committees were visited. Farmers were interviewed
      and premises and animals visually inspected on all farms. Feed samples were
      collected from a subset of farms. The most commonly kept species were water
      buffalo (used for milk and meat), cattle (used for milk and labor), and goats
      (used for meat). Average milk production levels were 4.7 kg/day for water buffalo
      and 1.9 kg/day for cattle. All animals were milked manually, no calves were
      weaned, and only one farm practiced artificial insemination. A majority of cattle
      and goats had access to pasture, and a majority of farms fed their working or
      producing animals concentrates; however, nutritional input was insufficient in
      terms of energy, protein, and micronutrient content to increase levels of
      production. Goat-raising was the most profitable endeavor, followed by water
      buffalo and cattle. We conclude that animals have the potential to contribute
      significantly to improved livelihoods of farmers in terms of both income
      generation and non-tangible benefits. However, we found that significant
      constraints on animal production exist, including insufficient nutritional levels
      and a lack of preventative care resulting in animal disease. Furthermore,
      cultural considerations reflecting attitudes toward cattle shape farming in ways
      that may limit production. Nevertheless, targeted interventions that improve
      animal health and productivity are possible without being cost prohibitive.

PMID- 22392550
TI  - Psychopathology and personality in parents of children with ADHD.
AB  - OBJECTIVE: To compare psychopathology and personality in parents of children with
      ADHD and control parents. METHOD: A total of 140 parents were subdivided
      according to presence and duration of ADHD. Assessment was based on various ADHD
      self-rating scales, the revised Symptom Checklist (SCL-90-R), the Patient Health
      Questionnaire (PHQ), and the revised NEO Five Factors Inventory (NEO-FFI).
      RESULTS: Parents with lifelong persistent ADHD were most abnormal on all
      dimensions of ADHD psychopathology, the SCL-90-R, the PHQ, and the neuroticism
      and conscientiousness dimensions of the NEO-FFI. The scores of parents with
      current ADHD approached those of parents with persistent ADHD on most dimensions,
      and both groups scored higher than did parents with either remitted ADHD or no
      ADHD, or controls. The scores of the latter three groups were not significantly
      different from each other. CONCLUSION: Among parents of children with ADHD,
      parents with lifelong persistent or current ADHD show highest scores of
      psychopathology.

PMID- 22392551
TI  - Training executive, attention, and motor skills: a proof-of-concept study in
      preschool children With ADHD.
AB  - OBJECTIVE: To examine whether cognitive enhancement can be delivered through play
      to preschoolers with ADHD and whether it would affect severity of ADHD symptoms.
      METHOD: Twenty-nine 4- and 5-year-old children and their parents participated in
      separate group sessions (3-5 children/group). Child groups were introduced games
      designed to enhance inhibitory control, working memory, attention, visuospatial
      abilities, planning, and motor skills. Parent groups were encouraged playing
      these games with their children at least 30 to 45 min/day and taught strategies
      for scaffolding difficulty levels and dealing with obstacles to daily playing.
      RESULTS: Parent ratings and session attendance indicated considerable
      satisfaction with the program. Parent (p < .001) and teacher (p = .003) ratings
      on the ADHD-Rating Scale-IV (ADHD-RS-IV) indicated significant improvement in
      ADHD severity from pre- to post-treatment, which persisted 3 months later.
      CONCLUSION: This play-based intervention for preschoolers with ADHD is readily
      implemented at home. Preliminary evidence suggests efficacy beyond the
      termination of active treatment.

PMID- 22392552
TI  - Brain cortical thickness in ADHD: age, sex, and clinical correlations.
AB  - OBJECTIVE: Longitudinal magnetic resonance imaging (MRI) studies have shown
      reduced cortical thickness (CT) in individuals with ADHD, but this abnormality
      disappears with age, suggesting developmental delay. However, cross-sectional MRI
      studies have shown reduced CT, suggesting abnormal development. The aim of this
      study was to compare whole-brain CT in male and female children, adolescents, and
      adults with ADHD with whole-brain CT in matched control participants. METHOD: MRI
      scans were performed on ADHD and control participants. RESULTS: CT data revealed
      differences in right hemisphere (RH) only. Reduced CT was observed predominantly
      in the frontoparietal region. However, increased CT was observed predominantly in
      the occipital lobe. The CT differences were correlated with severity of ADHD.
      Analysis of sex differences revealed that location, number, and magnitude of CT
      differences were different between males and females in each age group.
      CONCLUSION: These data support the hypothesis that anatomical abnormalities in
      ADHD represent abnormal development rather than developmental delay.

PMID- 22392553
TI  - Flow-independent 3D whole-heart vessel wall imaging using an interleaved T2
      preparation acquisition.
AB  - Current techniques to visualize the arterial vessel wall are limited in coverage
      because most of them are flow dependent. In this study, we present a novel
      technique for flow-independent vessel wall imaging that takes advantage of the
      differences in T2 relaxation time of arterial blood and surrounding tissues using
      the T2-preparation prepulse. The technique is based on the acquisition and
      subtraction of two data sets, one obtained with and one without T2-preparation
      prepulse. This approach allows for nulling the signal of arterial blood while
      maintaining signal from muscle and vessel wall. The result of the subtraction is
      a flow-independent black-blood vessel wall image. To minimize the motion
      sensitivity of the subtraction step, we developed an interleaved acquisition for
      the T2-preparation prepulse and non-T2-preparation prepulse images, which allows
      obtaining coronary vessel wall images from a whole-heart acquisition with minimal
      misregistration artefacts. In this article, we present the technique and
      preliminary results in healthy subjects.

PMID- 22392554
TI  - A way to stable, highly emissive fluorubine dyes: tuning the electronic
      properties of azaderivatives of pentacene by introducing substituted pyrazines.
AB  - Pentacene and its derivatives are among the most important examples of pi
      electron-rich molecules used in organic field effect transistors. The replacement
      of CH groups by nitrogen atoms opens an elegant way to generate highly electron
      deficient molecules, known as oligoazaacenes. We describe the synthesis and
      spectroscopic properties of two novel derivatives of this family, namely the
      zwitterionic and quinoidal conjugated forms of dihydro-5,6,7,12,13,14
      hexaazapentacene (fluorubine). We outline a powerful strategy to tune the
      electronic properties of these redox-active azaacenes by the selective
      introduction of substituted pyrazines. Their acidochromic and solvatochromic
      behaviour is investigated experimentally and interpreted with the help of
      theoretical calculations. The simple "exchange" of substituents or protonation is
      shown to significantly alter the spectroscopic and electronic properties of these
      remarkably stable pi-systems. Their exceptional optical properties, such as high
      fluorescence quantum yields combined with a redox-active behaviour, make them
      promising candidates for sensor materials. Additional marked features in the
      solid state, such as herringbone packing in combination with short pi-pi
      distances, will open access to electronic materials.

PMID- 22392555
TI  - Effect of clarithromycin and fluconazole on the pharmacokinetics of montelukast
      in human volunteers.
AB  - OBJECTIVE: Montelukast, a leukotriene receptor antagonist, is used in the
      treatment of asthma. The objective of the study reported here was to determine
      whether multiple doses of clarithromycin or fluconazole affect the
      pharmacokinetics of montelukast. METHODS: This was a four-phase cross-over study
      with a washout period of 2 weeks between phases. In phase 1, 12 volunteers
      received a single oral dose of 10 mg montelukast. In phase 2, the volunteers
      received a single, oral dose of 1,000 mg clarithromycin once daily for 2 days,
      followed by, on day 3, a single oral dose of 10 mg montelukast co-administered
      with clarithromycin. In phase 3, a single oral dose of 50 mg fluconazole was
      given once daily for 6 days, followed by, on day 7, a single oral dose of 10 mg
      montelukast co-administered with 50 mg fluconazole. In the last phase (phase 4),
      a single oral dose of 150 mg fluconazole was given once daily for 6 days,
      followed by, on day 7, a single oral dose of 10 mg montelukast co-administered
      with 150 mg fluconazole. The plasma concentration of montelukast was measured by
      high performance liquid chromatography for 24 h. RESULTS: Following
      clarithromycin co-administration, the area under the concentration-time curve
      from zero to infinity ( AUC(0-infinity)) of montelukast increased by 144% [90%
      confidence interval (CI) 2.03-2.86]. The co-administration of a single oral dose
      of 150 and 50 mg fluconazole decreased the montelukast AUC(0-infinity) by 30.7
      (90% CI 0.53-0.81) and 38.8% (90% CI 0.57-0.69), respectively. CONCLUSIONS:
      Clarithromycin increased the plasma concentrations of montelukast whereas
      fluconazole reduced the plasma concentrations of montelukast. The mechanism of
      the interaction is probably due to interference of the interacting drugs with
      transporters mediating the uptake of montelukast.

PMID- 22392556
TI  - Variability of antimicrobial prescribing in patients with acute cellulitis.
AB  - PURPOSE: Clinical guidelines concerning treatment of infection are incorporated
      into prescribing formularies and antimicrobial stewardship policies. The extent
      to which these influence prescribing is uncertain. In this study, we sought to
      examine antimicrobial prescribing patterns in patients with cellulitis. METHODS:
      Consecutive adults admitted to hospital due to acute cellulitis between 2008 and
      2010 were studied. Data collected were clinical and laboratory markers of sepsis,
      antimicrobial agent, route of administration, number of i.v. dosages, duration of
      antimicrobial treatment, and hospital length of stay. Three groups were defined
      by prescribing that was (i) identical to formulary, (ii) modified appropriately
      due to microbiological data or prior drug allergy, and (iii) nonformulary
      prescribing. Comparisons were made between groups using Mann-Whitney tests.
      RESULTS: There were 306 patients: 167 men (54.6%), median age 66 (range 18-100)
      years. Prescribing was consistent with formulary recommendations in 253 (82.7%),
      modified appropriately in 24 (7.8%), and nonformulary in 29 (9.5%). Median
      [interquartile range (IQR)] duration of hospital stay was 5 (3-8), 7 (5-9, P =
      0.026), and 7 (5-14, P = 0.0006) days, and overall duration of antimicrobial
      therapy was 12 (9-16), 13 (8-15), and 15 (12-19, P = 0.0479) days, respectively.
      No differences were observed in clinical or laboratory markers of sepsis.
      CONCLUSIONS: Prescribing patterns accorded with prevailing guidelines in the
      majority of patients. Nonetheless, there was nonformulary prescribing in 10% of
      patients, and this could not be explained by clinical or laboratory measures of
      disease severity. Further work is needed to explore the factors that contribute
      to nonformulary prescribing in this group of patients.

PMID- 22392557
TI  - Modelling drug-related morbidity in Sweden using an expert panel of physicians.
AB  - PURPOSE: In modelling studies using pharmacists' opinions, drug-related morbidity
      (DRM) and preventable DRM have been more common than in observational studies,
      and the resulting costs are extensive. Modelling studies' estimates may vary
      depending on informants' profession. The purpose of this modelling study was to
      estimate the proportion of patients with DRM and preventable DRM and the cost of
      illness (COI) of DRM in Sweden based on physicians' expert opinions. METHOD: A
      conceptual model of DRM was modified from previous studies. Using a modified
      Delphi technique, a panel of physicians (n = 19) estimated the probabilities of
      DRM, preventable DRM, and clinical outcomes of DRM separately for outpatients and
      inpatients. DRM included new medical problems (adverse drug reactions, drug
      dependence, and intoxications by overdose) and therapeutic failure (insufficient
      effects of medicines, and morbidity due to untreated indication). A COI analysis
      included the direct costs of DRM. RESULTS: Physicians estimated that 51 +/- 22%
      [mean +/- standard deviation (SD)] of outpatients experience DRM and 12 +/- 8%
      preventable DRM. Of inpatients, 54 +/- 17% was estimated to experience DRM and 16
      +/- 7% preventable DRM. Of outpatients with DRM, 24 +/- 11% was estimated to
      experience preventable DRM, whereas this proportion for inpatients was 31 +/-
      15%. The estimated COI was 376 euros per outpatient and 838 euros per inpatient.
      CONCLUSIONS: Swedish physicians estimated that every other outpatient and
      inpatient experiences DRM, which is often preventable and costly. As physicians'
      estimates on the proportion of patients with DRM were higher than in
      observational studies in restricted subpopulations, DRM may be more common in the
      general population than observational studies suggest.

PMID- 22392558
TI  - Prescribing errors intercepted by clinical pharmacists in paediatrics and
      obstetrics in a tertiary hospital in Spain.
AB  - PURPOSE: To assess the main differences in clinical significance of the
      prescribing errors intercepted by clinical pharmacists in paediatrics and
      obstetrics and the reasons for these prescribing errors, as well as the
      differences in pharmacists' activity indicators. METHODS: The was a cross
      sectional epidemiological study analysing the activities of paediatric
      pharmacists in a maternity and children's hospital with 180 paediatric beds and
      138 obstetrics and gynaecology beds between January 2007 and December 2009. The
      following variables were analysed: clinical significance of prescribing errors
      intercepted, reason for the error, impact of the intervention by pharmacist,
      acceptance rate of the recommendation made, medication involved, intervention
      detection date and observations. RESULTS: A total of 2,449 interventions in
      medical orders were recorded. Interventions that were not accepted by doctors
      were excluded, leaving 43 cases (2.1%) of extremely significant interventions and
      170 (8.4%) very significant interventions. Interventions in what were deemed to
      be error-free situations were excluded. Significance testing (based on 2,035
      errors detected) showed that 1.7% of the detected errors were potentially lethal
      (35 cases), while 10.2% (210 cases) were clinically serious. The main reason for
      the interventions was the detection of a dosage between 1.5- and tenfold higher
      than the recommended dosage. The overall rate of acceptance of the pharmacist's
      suggestions was 92.2%. Pharmacists carried out an average of 0.016
      interventions/patient-day throughout the study period. CONCLUSIONS: Paediatric
      patients had a fourfold higher risk of serious errors than the maternity
      population. Pharmacist intervention had a major impact on reducing prescribing
      errors in the study period, thus improving the quality and efficiency of care
      provided.

PMID- 22392559
TI  - Outcome of anatomic transphyseal anterior cruciate ligament reconstruction in
      Tanner stage 1 and 2 patients with open physes.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) injuries are being seen with
      increasing frequency in children. Treatment of the ACL-deficient knee in
      skeletally immature patients is controversial. PURPOSE: To determine the outcome
      of all-arthroscopic transphyseal anatomic single-bundle ACL reconstruction in
      Tanner stage 1 and 2 patients at a minimum of 2 years after surgery. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: Between 2007 and 2008, 16
      prepubescent patients underwent ACL reconstruction using soft tissue grafts. All
      patients were Tanner stage 1 and 2. Outcomes were assessed at a minimum of 2
      years after surgery and included limb alignment, limb length, instrumented
      testing with the KT-1000 arthrometer, and International Knee Documentation
      Committee (IKDC) score. RESULTS: Mean age at the time of surgery was 12 years
      (range, 8-14 years). Graft choices included the following: living donor-related
      hamstring tendon allograft (n = 14), hamstring tendon autograft (n = 1), and
      fresh-frozen allograft (n = 1). Mean IKDC subjective score was 96 (range, 84
      100). All patients had a stable knee postoperatively. Eleven patients had a
      negative Lachman test result, and 14 had a negative pivot-shift test result. The
      remainder had grade 1 Lachman and pivot-shift test findings, respectively. At 2
      years after surgery, all patients had returned to strenuous activities, and
      normal or nearly normal overall IKDC score was documented in 94% of patients.
      There were no cases of limb malalignment or growth arrest. CONCLUSION: We present
      a case series of transphyseal anatomic single-bundle ACL reconstruction in Tanner
      stage 1 and 2 patients at a minimum of 2 years after surgery. Excellent clinical
      outcomes were obtained with high levels of return to desired activities.
      Importantly, no growth disturbances were seen in this series of patients.

PMID- 22392560
TI  - Alterations in internal rotation and alpha angles are associated with
      arthroscopic cam decompression in the hip.
AB  - BACKGROUND: Symptomatic labral tears of the hip are associated with bony
      abnormalities of the femoral head and acetabulum, resulting in impingement. These
      patients have characteristic internal rotation limitations, which can result in
      compensatory athletic injury patterns around the hip, pelvis, and lumbar spine.
      HYPOTHESIS: Patients undergoing arthroscopic cam decompression will have
      improvement in internal rotation after decompression. Patients with decreased
      femoral neck anteversion will have decreased preoperative internal rotation of
      the hip and show less improvement after cam decompression. STUDY DESIGN: Cohort
      study; Level of evidence, 3. METHODS: Patients undergoing arthroscopic
      decompression of cam and pincer lesions of the hip and treatment of labral injury
      were evaluated for range of motion and bony anatomy by preoperative computed
      tomography and pre- and postoperative radiographs. Patients were excluded for age
      older than 40 years, arthritic changes of the joint, and revision setting.
      RESULTS: Fifty-five patients (56 hips) were treated with selective labral
      debridement with functional labral preservation (33/56) or selective labral
      debridement with labral refixation (23/56) and cam decompression. Fifty-one of
      the 56 had resection of associated pincer lesions. Patients were divided into
      femoral anteversion subgroups: normal (5 degrees -20 degrees , 34 patients),
      increased (>20 degrees , 8 patients), and decreased (<5 degrees , 13 patients).
      Mean patient age was 24.7 +/- 6.3 years (range, 14-39 years). Alpha angle, a
      measure of the head-neck offset, decreased from 68.0 degrees  +/- 10.0 degrees 
      preoperatively to 43.4 degrees  +/- 4.0 degrees  after decompression (P < .001).
      Internal rotation of the hip increased from 9.9 degrees  +/- 6.6 degrees 
      preoperatively to 27.6 degrees  +/- 6.4 degrees  after decompression (P < .001)
      and 30.1 degrees  +/- 5.3 degrees  at 3 months (P < .001). Hip flexion was not
      significantly different immediately after decompression but was significantly
      improved from 115.7 degrees  +/- 13.3 degrees  preoperatively to 127.9 degrees 
      +/- 6.6 degrees  at 3 months postoperatively (P < .003). Although improvement in
      internal rotation after decompression increased independent of femoral version,
      patients with abnormal version had altered internal rotation with increased
      values associated with increased anteversion (15.7 degrees  +/- 5.4 degrees /34.3
      degrees  +/- 6.7 degrees ) and decreased with relative retroversion (7.1 degrees 
      +/- 8.3 degrees /25.2 degrees  +/- 4.9 degrees ; P < .05). CONCLUSION:
      Arthroscopic decompression results in improvement of the radiographic alpha angle
      and normalization of internal rotation in impingement-related disease of the hip.
      Internal rotation improvements can be achieved even in the setting of femoral
      retroversion.

PMID- 22392561
TI  - The effect of dynamic femoroacetabular impingement on pubic symphysis motion: a
      cadaveric study.
AB  - BACKGROUND: A link between femoroacetabular impingement and athletic pubalgia has
      been reported clinically. One proposed origin of athletic pubalgia is secondary
      to repetitive loading of the pubic symphysis, leading to instability and
      parasymphyseal tendon and ligament injury. Hypothesis/ PURPOSE: The purpose of
      this study was to investigate the effect of simulated femoral-based
      femoroacetabular impingement on rotational motion at the pubic symphysis. The
      authors hypothesize that the presence of a cam lesion leads to increased relative
      symphyseal motion. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve
      hips from 6 fresh-frozen human cadaveric pelvises were used to simulate cam-type
      femoroacetabular impingement. The hips were held in a custom jig and maximally
      internally rotated at 90 degrees  of flexion and neutral adduction. Three
      dimensional motion of the pubic symphysis was measured by a motion-tracking
      system for 2 states: native and simulated cam. Load-displacement plots were
      generated between the internal rotational torque applied to the hip and the
      responding motion in 3 anatomic planes of the pubic symphysis. RESULTS: As the
      hip was internally rotated, the motion at the pubic symphysis increased
      proportionally with the degrees of the rotation as well as the applied torque
      measured at the distal femur for both states. The primary rotation of the
      symphysis was in the transverse plane and on average accounted for more than 60%
      of the total rotation. This primary motion caused the anterior aspect of the
      symphyseal joint to open or widen, whereas the posterior aspect narrowed. At the
      torque level of 18.0 N.m, the mean transverse rotation in degrees was 0.89
      degrees  +/- 0.35 degrees  for the native state and 1.20 degrees  +/- 0.41
      degrees  for cam state. The difference between cam and the native groups was
      statistically significant (P < .03). CONCLUSION: Dynamic femoroacetabular
      impingement as caused by the presence of a cam lesion causes increased rotational
      motion at the pubic symphysis. CLINICAL RELEVANCE: Repetitive loading of the
      symphysis by cam impingement is thought to lead to increased symphyseal motion,
      which is one possible precursor to athletic pubalgia.

PMID- 22392562
TI  - A high-speed drug interaction search system for ease of use in the clinical
      environment.
AB  - With the advancement of pharmaceutical development, drug interactions have become
      increasingly complex. As a result, a computer-based drug interaction search
      system is required to organize the whole of drug interaction data. To overcome
      problems faced with the existing systems, we developed a drug interaction search
      system using a hash table, which offers higher processing speeds and easier
      maintenance operations compared with relational databases (RDB). In order to
      compare the performance of our system and MySQL RDB in terms of search speed,
      drug interaction searches were repeated for all 45 possible combinations of two
      out of a group of 10 drugs for two cases: 5,604 and 56,040 drug interaction data.
      As the principal result, our system was able to process the search approximately
      19 times faster than the system using the MySQL RDB. Our system also has several
      other merits such as that drug interaction data can be created in comma-separated
      value (CSV) format, thereby facilitating data maintenance. Although our system
      uses the well-known method of a hash table, it is expected to resolve problems
      common to existing systems and to be an effective system that enables the safe
      management of drugs.

PMID- 22392563
TI  - Physicians' views and assessments on picture archiving and communication systems
      (PACS) in two Turkish public hospitals.
AB  - A picture archiving and communication system (PACS) is a medical imaging
      technology which provides economical storage of and convenient access to images
      from multiple modalities (source machine types). PACS have been widely introduced
      as a credible alternative to the traditional film-based radiological service.
      This study was planned and conducted to determine the physicians' views and
      assessments on PACS in two public hospitals in Turkey. A questionnaire was
      prepared by viewing the literature related to PACS. The questionnaires were
      distributed several times to a total of 150 physicians two public hospitals in
      Ankara, Turkey. The overall response rate is 46%. Some questions required a
      graduated score in response and others an open ended response. The majority of
      physicians judged PACS to be a major advance for their hospitals with less
      frustration than using film high quality images and an improvement in their
      working lives and patient care. They reported that PACS gave them to radiology
      reports in short time. Also physicians believed that PACS has improved their
      consultations. Open ended questions were prepared with concerning the benefits
      and disadvantages of PACS. The assessments of the physicians demonstrated many
      more benefits than disadvantages of PACS in their hospitals. PACS has been
      accepted well by a wide percentage of hospital physicians. PACS evolves over time
      components are frequently replaced and so the users must expect continuous
      learning about new updates and improved functionality. The implementation of the
      PACS clearly contributes to an increase in the productivity of health
      professionals and physicians.

PMID- 22392564
TI  - An improved medical decision support system to identify the diabetic retinopathy
      using fundus images.
AB  - An improved Computer Aided Clinical Decision Support System has been developed to
      classify the retinal images using Neural Network and presented in this paper. The
      Optic Disc Parameters, thickness of the blood vessels, main vessel, and branch
      vessel and vein diameter have been extracted. Various types of Neural Network
      have been used for classification. The percentage of False Acceptance Rate and
      False Rejection Rate of the SVM classifier is found less than other classifiers.
      The accuracy of the proposed system has been verified and found to be 97.47%.

PMID- 22392565
TI  - Favorable survival maintained in children who have myeloid leukemia associated
      with Down syndrome using reduced-dose chemotherapy on Children's Oncology Group
      trial A2971: a report from the Children's Oncology Group.
AB  - BACKGROUND: Children who are treated for myeloid leukemia associated with Down
      syndrome (DS) experience superior survival compared with children who have
      myeloid leukemia without DS. To maintain excellent outcomes while avoiding
      toxicity, the Children's Oncology Group (COG) conducted the phase 3 trial COG
      A2971, the first trial solely designed to provide uniform treatment of myeloid
      leukemia in North American children with DS. A2971 eliminated 2 induction drugs
      and 3 months of maintenance therapy from the standard-timing regimen of
      dexamethasone, cytarabine, 6-thioguanine, etoposide, and rubidomycin/daunomycin
      (DCTER) used in the previous study (Children's Cancer Group [CCG] 2891). METHODS:
      COG A2971 was a multi-institutional, nonrandomized, clinical trial that enrolled
      132 patients who had DS with either acute myeloid leukemia (n = 91) or
      myelodysplastic syndrome (n = 41). RESULTS: The median follow-up was 4.8 years
      (range, 0.8-8.6 years), the median age at diagnosis was 1.7 years (range, 0.3
      13.6 years), and the median white blood cell count was 6200/MUL (range, 900
      164,900/MUL). The remission rate (92.7% +/- 6%) was similar to that reported in
      the CCG 2891 study (91.3% +/- 5%; P = .679). The 5-year event free survival (EFS)
      rate was 79% +/- 7% (vs 77% +/- 7% in CCG 2891; P = .589), the disease-free
      survival (DFS) rate was 89% +/- 6% (vs 85% +/- 6% in CCG 2891; P = .337), and the
      overall survival rate was 84% +/- 6% (vs 79% +/- 7% in CCG 2891; P = .302).
      Induction day-14 bone marrow response trended toward a more favorable outcome
      (EFS: P = .12). Age >4 years was an adverse risk factor (5-year EFS rate: 33% +/-
      38% for children aged >4 years [median, 8.5 years; n = 6] vs 81% +/- 7% for
      children ages 0-4 years [median, 1.7 years; n = 126]; P = .001). CONCLUSIONS: The
      COG A2971 trial reduced the chemotherapy dose and maintained survival to that
      achieved by the CCG 2891 trial in children who had myeloid leukemia associated
      with DS.

PMID- 22392566
TI  - IgG glycan hydrolysis by endoglycosidase S diminishes the proinflammatory
      properties of immune complexes from patients with systemic lupus erythematosus: a
      possible new treatment?
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease with
      chronic or episodic inflammation in several organ systems, related to the
      presence of circulating and tissue-deposited immune complexes (ICs) that
      stimulate leukocytes through Fcgamma receptors (FcgammaR) with subsequent
      inflammation. Treatment with endoglycosidase S (EndoS), an IgG glycan-hydrolyzing
      bacterial enzyme from Streptococcus pyogenes, has shown beneficial effects in
      several experimental animal models of chronic inflammatory disease. This study
      was undertaken to investigate whether EndoS affects the proinflammatory
      properties of ICs and has the potential to be developed as a therapy for SLE.
      METHODS: ICs purified from SLE patients or RNA-containing ICs formed in vitro
      were treated with EndoS and used in several assays reflecting different important
      features of SLE pathogenesis, such as phagocytosis by polymorphonuclear cells
      (PMNs) and plasmacytoid dendritic cells (PDCs), complement activation, and
      interferon-alpha (IFNalpha) production by PDCs. RESULTS: EndoS treatment
      abolished all proinflammatory properties of the ICs investigated. This included
      FcgammaR-mediated phagocytosis by PDCs (P = 0.001) and subsequent production of
      IFNalpha (P = 0.002), IC-induced classical pathway of complement activation (P =
      0.008), chemotaxis, and oxidative burst activity of PMNs (P = 0.002). EndoS
      treatment also had a direct effect on the molecular structure of ICs, causing
      decreased IC size and glycosylation. CONCLUSION: Our findings indicate that EndoS
      treatment has prominent effects on several pathogenetically important IC-mediated
      events, and suggest that EndoS has the potential to be developed as a novel
      therapy for SLE.

PMID- 22392567
TI  - Effects of dexmedetomidine on conditioned pain modulation in humans.
AB  - BACKGROUND: Systemic administration of dexmedetomidine (DEX; selective alpha(2) 
      adrenoceptor agonist) is found to inhibit diffuse noxious inhibitory control in
      rats, now referred to as conditioned pain modulation (CPM) in humans. The present
      study was designed to investigate the effect of intravenous administration of DEX
      on CPM in humans. METHODS: There were two sequential sessions in this double
      blind, randomized study. The first session was the control with normal saline
      infusion (N(1st), L(1st), H(1st)). During the second session, three types of
      agents were infused: normal saline (N(2nd)); a low plasma concentration of DEX
      (0.04 ng/mL; L(2nd)); and a high plasma concentration of DEX (0.08 ng/mL;
      H(2nd)). The amplitude of somatosensory evoked potentials (ampSEP)s and the
      visual analogue scale of tooth pain (VASt) induced by electrical tooth
      stimulation were evaluated with and without conditioning CO(2) laser stimulation
      of the hand. The inhibition rate (% inhibition) was calculated [= (1-[ampSEP or
      VASt with conditioning stimuli]/[ampSEP or VASt without conditioning stimuli]) *
      100] to compare the magnitude of the DEX effects on CPM. RESULTS: The inhibition
      rates of ampSEPs and VASt in Types N, L and H varied significantly, demonstrating
      a dose-dependent reduction of CPM effects of ampSEP and VASt during randomized
      DEX administration, consistent with results from animal studies. CONCLUSIONS: The
      present study shows that systemic administration of an alpha(2) -adrenoceptor
      agonist (DEX), less than the clinical dose, inhibited CPM in humans. These
      results may provide some mechanistic insight into why many chronic pain patients
      show impaired CPM.

PMID- 22392568
TI  - Primary mixed neuroendocrine carcinoma of the bladder with large cell component:
      a case report and review of the literature.
AB  - Primary large cell neuroendocrine carcinomas (NECs) of the bladder are rarely
      encountered, and only a few reports have been documented. Frequently, they are
      found to be admixed with other histologies. In this report, we describe such a
      tumor found in a 65-year-old man who underwent radical cystectomy, after initial
      transurethral resection discovered a small cell NEC pathology. We also reviewed
      the limited number of neuroendocrine tumors reported containing a large cell
      component. Given the paucity of these tumors and the resultant difficulty in
      developing generalized treatment protocols, we promote the use of gene expression
      models to tailor chemotherapeutic regimens for individual tumors.

PMID- 22392569
TI  - BMD screening in older women: initial measurement and testing interval.

PMID- 22392570
TI  - The burden of stress in head and neck cancer.
AB  - BACKGROUND: Head and neck cancer (HNCa) introduces numerous stressors. We
      developed the Cancer-Related Stressors Checklist (CRSC), which documents exposure
      to seven categories of common stressors and emotional distress. We surveyed HNCa
      survivors and examined associations among exposure to cancer-related stressors,
      illness intrusiveness (i.e., cancer-induced interference with lifestyles,
      activities, and interests), and distress. We also investigated whether reported
      exposure rates differ between self-administered and interviewer-administered
      measures. METHODS: Respondents included HNCa survivors, stratified by sex, who
      participated in one of two clinical studies (N1  = 162; N2  = 408) examining the
      psychosocial impact of illness intrusiveness. All completed the CRSC, the Center
      for Epidemiologic Studies Depression Scale, and the Illness Intrusiveness Ratings
      Scale. Study 1 respondents self-administered the instruments; an interviewer
      administered them in Study 2. We gathered clinical data by self-report and from
      medical records. RESULTS: High inter-rater reliability corroborated the 8
      subscale structure of the CRSC (Krippendorff alpha = .92). Cancer-related
      stressor exposures differed significantly across categories (interpersonal
      stressors were most common). Controlling for empirically identified covariates
      and distress, exposure to each cancer-related stressor correlated significantly
      and uniquely with illness intrusiveness. All stressor categories correlated
      significantly with distress, but coefficients were low to moderate,
      substantiating incremental validity. Respondents reported fewer exposures when
      materials were self-administered as compared with interviewer-administered, but
      reported distress levels did not differ by mode of administration. CONCLUSIONS:
      Cancer-related stressors are common and burdensome in HNCa and, therefore, merit
      clinical attention. Identifying specific stressors will allow more targeted and
      effective interventions to alleviate and prevent distress.

PMID- 22392572
TI  - Phase I study of AEE788, a novel multitarget inhibitor of ErbB- and VEGF-receptor
      family tyrosine kinases, in recurrent glioblastoma patients.
AB  - PURPOSE: Vascular endothelial growth factor receptor (VEGFR) and epidermal growth
      factor receptor (EGFR) play a significant role in glioblastoma angiogenesis and
      proliferation, making tyrosine kinase (TK) receptors logical targets for
      treatment. We evaluated AEE788, a reversible TK inhibitor that inhibits EGFR and
      VEGFR, in recurrent glioblastoma patients. METHODS: In this dose-escalation,
      phase I study, patients with recurrent glioblastoma received AEE788 once daily in
      28-day cycles in stratified subgroups: those receiving (1) non-enzyme-inducing
      anticonvulsants drugs or no anticonvulsants (Group A) and (2) enzyme-inducing
      anticonvulsant drugs (Group B). A dose-expansion phase stratified patients by
      surgical eligibility. Primary objectives were to determine dose-limiting toxicity
      (DLT) and maximum tolerated dose; secondary objectives included evaluating (1)
      safety/tolerability, (2) pharmacokinetics, and (3) preliminary antitumor
      activity. RESULTS: Sixty-four glioblastoma patients were enrolled. Two Group A
      patients experienced DLTs (proteinuria and stomatitis) at 550 mg; 550 mg was,
      therefore, the highest dose evaluated and dose limiting. One Group B patient
      receiving 800 mg experienced a DLT (diarrhea). The initially recommended dose for
      dose-expansion phase for Group A was 400 mg; additional patients received 250 mg
      to assess the hepatotoxicity. Most frequently reported adverse events (AEs)
      included diarrhea and rash. Serious AEs, most commonly grade 3/4 liver function
      test elevations, were responsible for treatment discontinuation in 17% of
      patients. AEE788 concentrations were reduced by EIACD. The best overall response
      was stable disease (17%). CONCLUSIONS: Continuous, once-daily AEE788 was
      associated with unacceptable toxicity and minimal activity for the treatment of
      recurrent glioblastoma. The study was, therefore, discontinued prematurely.

PMID- 22392573
TI  - Pre-operative progressive pneumoperitoneum for repair of a large incisional
      hernia.
AB  - Large incisional hernias are difficult to treat surgically because of the post
      operative respiratory complications and abdominal compartment syndrome. Pre
      operative progressive pneumoperitoneum is a technique which has been used in such
      cases. We describe a case of a large incisional hernia, where this technique was
      employed by objectively calculating abdominal and hernial sac volumes on the
      basis of computerized tomography scan of abdomen with a satisfactory outcome. A
      review of literature and issues involved in pre-operative progressive
      pneumoperitoneum have been discussed.

PMID- 22392574
TI  - Inguinoscrotal extension of a pancreatic collection: a rare complication of
      pancreatitis-case report and review of the literature.
AB  - Pancreatitis associated with the extension of a pancreatic collection, pseudocyst
      or abscess into the groin is a rare phenomenon with few reports in the English
      literature. Nevertheless, it remains a clinically important differential
      diagnosis as it may be mistaken for more common pathologies in the groin and with
      a subsequent unnecessary surgical intervention. A case of this rare complication
      of pancreatitis is reported, together with a review of the literature.

PMID- 22392575
TI  - Combined endo-laparoscopic approach in a patient with a duodenal foreign body and
      bowel obstruction.
AB  - We report the successful removal of an intraduodenal foreign body (f.b.) by endo
      laparoscopic rendezvous, in a 67-year-old patient with mental disorders and
      duodenal occlusion by a large peach seed impacted in the duodenum. During a first
      endoscopic diagnostic evaluation it was possible to retract the peach seed into
      the stomach and have a confirmation of a stenosis of the second portion of the
      duodenum. Otherwise, the endoscopic procedure failed during removal out of the
      esophagus due to the large size of the f.b., and a second treatment in general
      anesthesia was planned. A 4 cm anterior gastrotomy was than performed by
      laparoscopy, and with a real endo-laparoscopic rendezvous, the peach seed out of
      the stomach was positioned, avoiding any intra-gastric surgical manouver and
      directly passing from Dormia basket into laparoscopic plastic retrieval bag. The
      gastrotomy was than closed with a single cartridge of a linear stapler and
      reinforced with an oversewn suture.

PMID- 22392576
TI  - Bowel function and fecal continence after Soave's trans-anal endorectal pull
      through for Hirschsprung's disease: a local experience.
AB  - The aim of this study was to evaluate the postoperative clinical outcome,
      colorectal function, and fecal continence score after Soave's transanal
      endorectal pull-through surgery (TERPT) for Hirschsprung's disease (HD) comparing
      them in preschool and school children with the results of younger children. This
      comparative retrospective study was done on 40 HD children treated over a period
      of 8 years from January 2001 to December 2008. Patients were classified into two
      equal groups according to their age: group I (n = 20) included children with age
      <6 months up to 42 months, and group II (n = 20) included children from 3.5 years
      up to 13 years. Demographic, clinical data, preoperative investigations,
      operative records, postoperative outcome and follow-up including defecation
      problems, fecal continence score rate (FCSR), anal manometry and electromyography
      were all reviewed. Obtained data were statistically analyzed using SPSS. Forty
      patients were included in this study, 28 males and 12 females with the male to
      female ratio of 2.3:1. The median age of the studied patients in group I was 8.9
      months, while in group II, the median age was 65.95 months. The postoperative
      follow-up period ranged from 18 to 24 months in group I with a mean of 21 months,
      while it ranged from 2 to 26 months in group II. In group I, most of children
      showed no abnormal defecation problems, 16 patients had excellent FCSR, 4 were
      having good FCSR and no poor continence score rate, while 3 patients suffered
      from constipation. Meanwhile, in group II, 15 patients showed excellent FCSR in
      10 patients and 5 with good FCSR. While the rest of patients suffered from
      different abnormal defecation behavior that was constipation in 5 patients. The
      remaining 5 patients suffered from continence problems varying from fair in 3
      patients (20%), with the remaining 2 patients having a poor continence score
      rate. It can be concluded that TERPT can be performed with some difficulties in
      older children; yet, the follow-up results are statistically low when compared
      with those patients who had undergone the operation at younger age.

PMID- 22392577
TI  - Forty-nine colorectal cancer liver metastases in one-stage hepatectomy with
      cumulative Pringle time lasting 348 min.

PMID- 22392578
TI  - Non-cirrhotic liver tolerance to intermittent inflow occlusion during
      laparoscopic liver resection.
AB  - While inflow occlusion techniques are accepted methods to reduce bleeding during
      open liver surgery, their use in laparoscopic liver resections are limited by
      possible effects of pneumoperitoneum on ischemia-reperfusion liver damage. This
      retrospective study was designed to investigate the impact of intermittent
      pedicle clamping (IPC) on patients with normal liver undergoing minor
      laparoscopic liver resections. Three matched groups of patients were
      retrospectively selected from our in-house database: 11 patients who underwent
      robot-assisted liver resection with IPC, and 16 and 11 patients who underwent
      robot-assisted liver resection without IPC and open liver resection with IPC,
      respectively. The primary end point was to assess differences in postoperative
      serum alanine, aspartate aminotransferase (ALT and AST) and bilirubin levels. The
      curves of serum AST, ALT and bilirubin levels in a span of time of five
      postoperative days were not significantly different between the three groups. IPC
      has no relevant effects on ischemia-reperfusion liver damage even in the presence
      of pneumoperitoneum.

PMID- 22392580
TI  - Spontaneous recovery from anti-NMDAR encephalitis.

PMID- 22392579
TI  - Health-related quality of life in Huntington's disease patients: a comparison of
      proxy assessment and patient self-rating using the disease-specific Huntington's
      disease health-related quality of life questionnaire (HDQoL).
AB  - Huntington's disease (HD) is a fatal, neurodegenerative disease for which there
      is no known cure. Proxy evaluation is relevant for HD as its manifestation might
      limit the ability of persons to report their health-related quality of life
      (HrQoL). This study explored patient-proxy ratings of HrQoL of persons at
      different stages of HD, and examined factors that may affect proxy ratings. A
      total of 105 patient-proxy pairs completed the Huntington's disease health
      related quality of life questionnaire (HDQoL) and other established HrQoL
      measures (EQ-5D and SF-12v2). Proxy-patient agreement was assessed in terms of
      absolute level (mean ratings) and intraclass correlation. Proxies' ratings were
      at a similar level to patients' self-ratings on an overall Summary Score and on
      most of the six Specific Scales of the HDQoL. On the Specific Hopes and Worries
      Scale, proxies on average rated HrQoL as better than patients' self-ratings,
      while on both the Specific Cognitive Scale and Specific Physical and Functional
      Scale proxies tended to rate HrQoL more poorly than patients themselves. The
      patient's disease stage and mental wellbeing (SF-12 Mental Component scale) were
      the two factors that primarily affected proxy assessment. Proxy scores were
      strongly correlated with patients' self-ratings of HrQoL, on the Summary Scale
      and all Specific Scales. The patient-proxy correlation was lower for patients at
      moderate stages of HD compared to patients at early and advanced stages. The
      proxy report version of the HDQoL is a useful complementary tool to self
      assessment, and a promising alternative when individual patients with advanced HD
      are unable to self-report.

PMID- 22392581
TI  - Genetic variants of the MRC1 gene and the IFNG gene are associated with leprosy
      in Han Chinese from Southwest China.
AB  - Leprosy is an ancient infectious disease, with over 200,000 affected people
      (mainly in Asia and Africa) being registered annually. Genetic factors may confer
      susceptibility to this disease. In the present study, we genotyped 12 genetic
      variants of the MRC1 gene and the IFNG gene in 527 Han Chinese with leprosy and
      583 healthy individuals from Yunnan, China, to discern potential association of
      these two genes with leprosy. In particular, we aimed to validate the recently
      reported association of MRC1 variant rs1926736 (p.G396S) and IFNG variant
      rs2430561 (+874 T>A) with leprosy, which were initially observed in Vietnamese
      and Brazilian populations, respectively. Our results failed to confirm the
      reported association between variants rs1926736 and rs2430561 and leprosy in Han
      Chinese. However, we found that variants rs692527 (P = 0.022) and rs34856358 (P =
      0.022) of the MRC1 gene were associated with paucibacillary leprosy, and
      rs3138557 of the IFNG gene was significantly associated with multibacillary
      leprosy. The exact role of the MRC1 gene and the IFNG gene in leprosy awaits
      future study.

PMID- 22392582
TI  - Prenatal screening for beta-thalassemia major reveals new and rare mutations in
      the Pakistani population.
AB  - beta-Thalassemia is the most common genetic disorder in Pakistan, where more than
      6000 affected children are born annually, and the carrier population is around 10
      million. The objective was to study beta-globin gene mutations in chorionic
      villous biopsy samples. Prenatal screening of 383 pregnant women between 2003 and
      2010 was carried out using a panel of 13 mutation primers and amplification
      refractory mutations system (ARMS)-PCR. In addition, DNA sequencing was used to
      confirm uncharacterized mutations and in some cases fetal disease status was
      confirmed by linkage analysis. Families enrolled in this study represented major
      ethnic groups in Pakistan. Of the 13 mutations tested, three mutations accounted
      71% of the total, including IVS1-5(G-C)[HBB:c.92+5G>C], codon 8/9(+G)
      [HBB:c.27_28insG] and del 619[NG_000007.3:g71609-72227del619]. Mutations in four
      uncharacterized samples were later confirmed by DNA sequencing as -88(C-T)[HBB:c.
      138C>G], -90(C-T)[HBB:c.-140C>T] and codon 59(+T)[HBB:c.178_179insT]. To our
      knowledge, this is the first report of these mutations in Pakistan. Moreover,
      19.2% fetal samples were normal and 52.3% heterozygous, whereas 26.4% were
      affected with thalassemia major. IVS1-5:IVS1-5 was the most common genotype in
      fetal samples. Prenatal diagnosis of beta-thalassemia using ARMS PCR is an
      efficient approach for reducing the burden of this disease in Pakistan. In
      addition, rare mutations reported in this study should be incorporated in the
      diagnostic strategy.

PMID- 22392583
TI  - Blood flow and anatomical MRI in a mouse model of retinitis pigmentosa.
AB  - This study tested the sensitivity of an arterial spin labeling MRI method to
      image changes in retinal and choroidal blood flow (BF) and anatomical thickness
      of the retina in the rd10 mouse model of retinitis pigmentosa. High-resolution
      (42 * 42 MUm) MRI was performed on rd10 mice and age-matched controls at 25, 35,
      and 60 days of age (n = 6 each group) on a 7-T scanner. Anatomical MRI was
      acquired, and quantitative BF was imaged using arterial spin labeling MRI with a
      separate cardiac labeling coil. Histology was obtained to confirm thickness
      changes in the retina. In control mice, the retinal and choroidal vascular layers
      were quantitatively resolved. In rd10 mice, retinal BF decreased progressively
      over time, while choroidal BF was unchanged. The rd10 retina became progressively
      thinner at later time points compared with age-matched controls by anatomical MRI
      and histology (P < 0.01). BF and anatomical MRI were capable of detecting
      decreased BF and thickness in the rd10 mouse retina. Because BF is tightly
      coupled to metabolic function, BF MRI has the potential to noninvasively assess
      retinal diseases in which metabolism and function are perturbed and to evaluate
      novel treatments, complementing existing retinal imaging techniques.

PMID- 22392584
TI  - Patient advocates' role in clinical trials: perspectives from Cancer and Leukemia
      Group B investigators and advocates.
AB  - BACKGROUND: Patient advocates are increasingly involved in cooperative group
      trials, single-institution cancer programs, and peer-review of research
      applications. The purpose of this study was to evaluate the role and value of
      patient advocates from the perspective of Cancer and Leukemia Group B (CALGB)
      advocates and investigators. METHODS: An online survey was sent to current and
      past (within 5 years) patient advocates and investigators. RESULTS.: Response
      rates were 72.7% (16 of 22) for advocates and 56.4% (102 of 181) for
      investigators. Patient advocates were more likely than investigators to report
      the following: the clinical trial process benefited from advocate involvement on
      committees (100% of advocates vs 72.1% of investigators; P < .05), advocates
      contribute to protocol development (92.8% vs 33.8%, respectively; P < .001), the
      cultural appropriateness of protocols (21.4% vs 10.4%, respectively; P < .05),
      advocates assist with patient accrual (78.6% vs 23.4%, respectively; P < .001),
      and advocates add value to concept development and protocol review (100% vs
      63.2%, respectively; P < .001). Over half of advocates and investigators reported
      gaps in patient advocate knowledge and suggested that additional clinical trials
      training was needed. To improve clinical trials, advocates suggested their
      earlier involvement in protocol development and increased support from
      investigators. CALGB investigators recommended improving patient advocate
      selection and communication skills training: CONCLUSIONS: The majority of patient
      advocates and investigators perceived benefits from advocate involvement in the
      clinical trials process; patient advocates placed more value on their role than
      investigators. The current results indicated that strategies to improve advocacy
      training and advocate-investigator communication may further enhance the role of
      patient advocates, and future studies that clarify the role of advocates in the
      prioritization and development of protocol, consent, and education materials, and
      on patient accrual, are warranted.

PMID- 22392585
TI  - Tautomerisation of 2-substituted pyridines to N-heterocyclic carbene ligands
      induced by the 16 e- unsaturated [Tp(Me2)Ir(III)(C6H5)2] moiety.
AB  - The complex [Tp(Me2)Ir(C(6)H(5))(2)(N(2))] reacts with several 2-substituted
      pyridines to generate N-heterocyclic carbenes resulting from a formal 1,2
      hydrogen shift from C(6) to N. In this paper we provide a detailed report of the
      scope and the mechanistic aspects (both experimental and theoretical) of the
      tautomerisation of 2-substituted pyridines.

PMID- 22392586
TI  - Trends in life expectancy by education in Norway 1961-2009.
AB  - Educational attainment and longevity are strongly related. Large population
      studies covering long periods to provide evidence of trends in educational
      inequalities regarding life expectancy are scarce though, especially prior to the
      1980s. Our objective was to document changes in life expectancy by education in
      Norway in the period 1961-2009, and to determine whether the patterns differ
      between sexes. This is a register-based population study of all Norwegian
      residents over 34 years, with data from the National Central Population Registry
      and the National Education Database. For each calendar year during 1961-2009,
      death rates by 1 year age groups were calculated separately for each sex and
      three educational categories (primary, secondary and tertiary). Annual life
      tables were used to calculate life expectancy at age 35 (e ( 35 )) and survival
      probability for the three age-intervals 35-44, 45-64, and 65-90. All education
      groups increased their e ( 35 ) over time, but inequalities in e ( 35 ) between
      tertiary and primary educational categories widened 5.3 years for men and 3.2
      years for women during the study period. The probability for women with primary
      education to survive to age 64 did not improve from 1961 to 2009. The gain in
      life expectancy lagged about 10 years in lower compared to higher education
      groups which might suggest that improvements in life sustaining factors reach
      different segments of the population at different times. The widening of the gap
      seems to have partly tapered off over the last two decades, and the changes in
      life expectancy should be followed carefully in the future to document the
      development.

PMID- 22392587
TI  - Cross-cultural comparison of correlates of quality of life and health status: the
      Whitehall II Study (UK) and the Western New York Health Study (US).
AB  - Measures of quality of life (QoL) have been found to be predictors of mortality
      and morbidity; however, there is still limited understanding of the multifaceted
      nature of these measures and of potential correlates. Using two large populations
      from the UK and US, we aimed to evaluate and compare measured levels of QoL and
      the key factors correlated with these levels. Participants were 6,472 white
      subjects (1,829 women) from the Whitehall II Study (mean age 55.8 years) and
      3,684 white subjects (1,903 women) from the Western New York Health Study (mean
      age 58.7 years). QoL was assessed in both using the physical and mental health
      component summaries of the short form-36 questionnaire (SF-36). Analysis of
      covariance was used to compare gender-specific mean scores for the two
      populations across several potential correlates (including socio-demographic,
      lifestyle and co-morbidity factors). Levels of reported physical QoL tended to be
      higher in the UK population (51.2 vs. 48.6) while mental QoL was higher in the US
      group (53.1 vs. 51.1). Age, sleep duration and depressive symptoms were the main
      factors correlated with both physical and mental QoL in both samples. Increasing
      age was associated with poorer physical health but higher mental health scores in
      both populations (P<0.001). Sleep duration below 6 or above 8 h was associated
      with lower levels of QoL. Depressive symptoms were strongly associated with
      poorer mental health scores (P<0.001) while higher BMI, lower physical activity
      levels and presence of cardiovascular disease were associated with poorer
      physical health in both samples and gender (P<0.05). There were consistent
      findings for correlates of QoL in this cross-cultural comparison of two
      populations from the UK and US. Strongest associations were between lifestyle and
      co-morbidity factors and the physical health component of the SF-36 rather than
      the mental health component. This is a novel finding which warrants further
      consideration.

PMID- 22392588
TI  - Leisure time physical activity and risk of non-vertebral fracture in men and
      women aged 55 years and older: the Tromso Study.
AB  - Our aim was to examine associations between leisure time physical activity and
      risk of non-vertebral fractures in men and women aged >=55 years, with focus on
      the anatomical fracture location. Self-reported physical activity was registered
      in 3,450 men and 4,072 women aged 55-97 years at baseline in the Tromso Study,
      Norway, in 1994-1995. Non-vertebral fractures were registered through December
      31, 2009. During 75,546 person-years at risk, 1,693 non-vertebral fractures were
      identified. Risk of any non-vertebral fracture decreased with increasing physical
      activity level in men (P (trend) = 0.006) and non-significantly in women (P
      (trend) = 0.15), after adjustment for age, body mass index, height, smoking, and
      previous fracture. The reduced fracture risk was due to a reduced risk in the
      weight-bearing skeleton, particular at the hip, whereas risk of fracture in the
      non-weight-bearing skeleton was not related to physical activity. At weight
      bearing sites, an inverse relationship between physical activity and fracture
      risk was present in both sexes (P (trend) <= 0.013). Compared with sedentary
      subjects, the most active men and women had respectively 37% (HR = 0.63, 95% CI:
      0.45, 0.88) and 23% (HR = 0.77, 95% CI: 0.62, 0.95) reduced fracture risk in the
      weight-bearing skeleton. Physical activity is associated with reduced fracture
      risk at weight-bearing sites, with no associations at non-weight-bearing sites,
      in both sexes. Habitual physical activity is an important amendable approach to
      prevent hip fracture.

PMID- 22392589
TI  - High caloric intake, poor cognition and dementia: the Caerphilly Prospective
      Study.
AB  - To examine the hypothesis that caloric intake in mid-life is associated with
      later dementia or cognitive impairment not dementia (CIND). A prospective cohort
      study was conducted in Caerphilly, South Wales, United Kingdom. Men aged 45-59
      years were identified from the electoral roll and general practice. 2,512 men
      were examined between July 1979 until September 1983. Four follow-up examinations
      were conducted every 4-5 years until 2004. Participants were categorized on the
      basis of their average daily caloric intake over each of the first three phases.
      Outcomes were CIND and dementia ascertained at phase five (2004). 192 men (15% of
      1,248 participants at phase five) had CIND and 100 (8%) dementia. Age adjusted
      odds ratios demonstrated strongest associations between average energy
      consumption and vascular CIND or dementia (OR 1.62 95% CI 1.25-2.10). Adjustment
      for nutritional factors, vascular disease, diabetes, smoking, BP and BMI if
      anything increased the association (OR 1.64, 95% CI 1.03-2.60). After adjusting
      for social class, associations were attenuated and consistent with chance (OR
      1.48, 95% CI 0.92-2.38). When adjusted for social class, the previously observed
      association between caloric intake and cognitive outcomes is modest, consistent
      with chance, and may be due to residual confounding.

PMID- 22392590
TI  - Sex difference and the role of leptin in the association between high-sensitivity
      C-reactive protein and adiposity in two different populations.
AB  - Elevated high-sensitivity C-reactive protein (hs-CRP) concentration is associated
      with an increased risk of cardiovascular disease but this association seems to be
      largely mediated via conventional cardiovascular risk factors. In particular, the
      association between hs-CRP and obesity has been extensively demonstrated and
      correlations are stronger in women than men. We used fractional polynomials--a
      method that allows flexible modeling of non linear relations--to investigate the
      dose/response mathematical relationship between hs-CRP and several indicators of
      adiposity in Caucasians (Switzerland) and Africans (Seychelles) surveyed in two
      population-based studies. This relationship was non-linear exhibiting a steeper
      slope for low levels of hs-CRP and a higher level in women. The observed sex
      difference in the relationship between hs-CRP and adiposity almost disappeared
      upon adjustment for leptin, suggesting that these sex differences might be
      partially mediated, by leptin. All these relationship were similar in Caucasians
      and Africans. This is the first report on a non-linear relation, stratified by
      gender, between hs-CRP and adiposity.

PMID- 22392593
TI  - Intervertebral disc and macrophage interaction induces mechanical hyperalgesia
      and cytokine production in a herniated disc model in rats.
AB  - OBJECTIVE: The expression of proinflammatory factors such as tumor necrosis
      factor alpha (TNFalpha), interleukin-6 (IL-6), IL-8, and prostaglandin E(2)
      (PGE(2) ) is significantly correlated with the symptoms of herniated disc
      disease. Among the different types of immune cells, macrophages are frequently
      noted in the herniated disc tissue. We undertook this study to clarify the
      interaction of the intervertebral disc (IVD) and macrophages with regard to the
      production of TNFalpha, IL-6, IL-8, and PGE(2) . METHODS: We developed 2 animal
      models to assess the interactions of IVDs with macrophages in terms of TNFalpha,
      IL-6, IL-8, and PGE(2) production and pain-related behavior. We also cocultured
      IVDs and macrophages to assess the role of TNFalpha in IL-6, IL-8, and PGE(2)
      production. RESULTS: IVD autografts induced TNFalpha, IL-6, IL-8, and
      cyclooxygenase 2 (COX-2) messenger RNA (mRNA) up-regulation; macrophage
      infiltration was seen shortly after the autograft was implanted. A significant
      decrease was noted in the mechanical threshold of the ipsilateral paw following
      the up-regulation of TNFalpha, IL-6, IL-8, and COX-2 mRNA. Only IVD and
      macrophage cocultures resulted in IL-8 and PGE(2) up-regulation. TNFalpha up
      regulation was maximized before that of IL-6 and IL-8. TNFalpha neutralization
      attenuated production of IL-6 and PGE(2) , but not that of IL-8. Neutralization
      of TNFalpha and IL-8 significantly increased the paw withdrawal mechanical
      threshold in the IVD autograft and spinal nerve ligation model. CONCLUSION: IVD
      macrophage interaction plays a major role in sciatica and in the production of
      TNFalpha, IL-6, IL-8, and PGE(2) . TNFalpha is required for IL-6 and PGE(2)
      production, but not for IL-8 production, during IVD-macrophage interaction.
      Neutralization of TNFalpha and IL-8 can be a valuable therapy for herniated disc
      disease.

PMID- 22392594
TI  - Pediatric bilateral Morgagni-Larrey diaphragmatic hernia: is diagnosis with
      computed tomography required in the era of laparoscopic approach?

PMID- 22392595
TI  - Emotion regulation and anxiety disorders.
AB  - A growing body of research suggests that the construct of emotion regulation is
      important for understanding the onset, maintenance, and treatment of anxiety
      disorders. In this review, we provide a selective overview of this emerging field
      and highlight the major sources of evidence. First, evidence suggests that the
      construct of emotion regulation can be differentiated from the construct of
      emotion. Second, there is a large and consistent body of research demonstrating
      that emotion regulation strategies can modulate emotional responding, and this
      finding is observed in both behavioral and neuroimaging studies. Third, measures
      of emotion regulation explain incremental variance in measures of anxiety
      disorder symptoms not accounted for by measures of negative affect. Although the
      research implicating emotion regulation in the anxiety disorders is promising,
      future research will be necessary to further clarify causal mechanisms explaining
      how emotion regulation confers vulnerability for anxiety disorders and to improve
      the clarity and consistency of definitions of emotion regulation.

PMID- 22392596
TI  - Key articles of dietary interventions that influence cardiovascular mortality.
AB  - Lifestyle modifications, particularly diet, are a key component to the reduction
      of cardiovascular events. Diets high in carbohydrates and saturated fat have been
      shown to negatively affect blood cholesterol, thereby increasing the risk for
      cardiovascular disease (CVD). Dietary interventions that emphasize the
      consumption of whole grains, fruits, and vegetables have been shown to be
      successful in reducing cardiovascular risk. Clinical pharmacist practitioners
      need to be knowledgeable regarding lifestyle modifications, specifically dietary
      issues, to develop a comprehensive, effective, and evidence-based plan for
      patients who are either at risk for or who have established CVD. Numerous studies
      have been published over the past few years with regard to the rapidly growing
      field of dietary interventions that influence cardiovascular risk, and the amount
      of literature can be overwhelming. Thus we chose to focus our review on articles
      that assess changes in dietary patterns that affect overall mortality risk from
      CVD. As such, literature describing the impact of dietary factors that influence
      weight, lipid changes, or other risk factors alone were not included in this
      review. A group of practitioners with expertise and interest in CVD were involved
      in the compilation of this article.

PMID- 22392597
TI  - Detection methanogens in newly settled sediments from Xuanwu Lake in Nanjing,
      China.
AB  - Sediments from Xuanwu Lake have been dredged in the past 3 years to improve the
      water quality, but methanogenesis should still exist in the newly settled
      sediment. Methane production, methanogens, and physiochemical parameters were
      detected in the surface sediments (0-5 cm) and/or vertical sediments (0-21 cm,
      segmented at interval of 3 cm). Methane flux at water-air interface varied among
      five detected sites. Principal component analysis showed that CH(4) flux, content
      of water and the concentration of total nitrogen (TN), CH(4) and organic matters
      (OM) weighed most heavily on the component I in surface sediments while different
      patterns were observed for vertical sediments. The copy number of the 16S rRNA
      gene for bacteria was lower in the surface sediment (0-6 cm) than that in deeper
      sediments (12-21 cm), while 16S rRNA genes of Archaea were almost evenly
      distributed in the vertical sediments. Representatives belonging to the orders
      Methanobacteriales, Methanomicrobiales, and Methanosarcinales were detected in
      all samples of the vertical sediments, except that no members of the
      Methanococcales were detected in the samples at 0-6 cm. The level of
      Methanobacteriales reached a highest density at 18.1 * 10(4) copies g(-1) dry
      weight (dw) at 6-9 cm; for Methanosarcinales (76.89 * 10(6) copies g(-1) dw) and
      Methanococcales (82.70 * 10(3) copies g(-1) dw) at 12-15 cm, whereas for
      Methanomicrobiales (43.37 * 10(6) copies g(-1) dw) at 9-12 cm. Methanosarcinaceae
      and Methanosaetaceae reached to their highest densities at 6-9 and 9-12 cm,
      respectively. These data provided useful information for better understanding the
      methanogenesis in the newly settled sediments of a recently dredged lake.

PMID- 22392598
TI  - Isolation, culture and chondrogenic differentiation of canine adipose tissue- and
      bone marrow-derived mesenchymal stem cells--a comparative study.
AB  - In the dog, mesenchymal stem cells (MSCs) have been shown to reside in the bone
      marrow (bone marrow-derived mesenchymal stem cells: BM-MSCs) as well as in the
      adipose tissue (adipose tissue-derived stem cells: ADSCs). Potential application
      fields for these multipotent MSCs in small animal practice are joint diseases as
      MSCs of both sources have shown to possess chondrogenic differentiation ability.
      However, it is not clear whether the chondrogenic differentiation potential of
      cells of these two distinct tissues is truly equal. Therefore, we compared MSCs
      of both origins in this study in terms of their chondrogenic differentiation
      ability and suitability for clinical application. BM-MSCs harvested from the
      femoral neck and ADSCs from intra-abdominal fat tissue were examined for their
      morphology, population doubling time (PDT) and CD90 surface antigen expression.
      RT-PCR served to assess expression of pluripotency marker Oct4 and early
      differentiation marker genes. Chondrogenic differentiation ability was compared
      and validated using histochemistry, transmission electron microscopy (TEM) and
      quantitative RT-PCR. Both cell populations presented a highly similar morphology
      and marker expression in an undifferentiated stage except that freshly isolated
      ADSCs demonstrated a significantly faster PDT than BM-MSCs. In contrast, BM-MSCs
      revealed a morphological superior cartilage formation by the production of a more
      abundant and structured hyaline matrix and higher expression of lineage specific
      genes under the applied standard differentiation protocol. However, further
      investigations are necessary in order to find out if chondrogenic differentiation
      can be improved in canine ADSCs using different protocols and/or supplements.

PMID- 22392600
TI  - New types of reactivity of alpha,beta-unsaturated N,N-dimethylhydrazones:
      chemodivergent diastereoselective synthesis of functionalized
      tetrahydroquinolines and hexahydropyrrolo[3,2-b]indoles.
AB  - The indium trichloride-catalyzed reaction between aromatic imines and alpha,beta
      unsaturated N,N-dimethylhydrazones in acetonitrile afforded 1,2,3,4
      tetrahydroquinolines bearing a hydrazone function at C4 through a one-pot
      diastereoselective domino process that involves the formation of two C-C bonds
      and the controlled generation of two stereocenters, one of which is quaternary.
      This reaction constitutes the first example of an alpha,beta-unsaturated
      dimethylhydrazone that behaves as a dienophile in a hetero Diels-Alder reaction.
      The related reaction between anilines, aromatic aldehydes, and methacrolein
      dimethylhydrazone in CHCl(3) with BF(3)?Et(2)O as catalyst afforded
      polysubstituted 1,2,3,3a,4,8b-hexahydropyrrolo[3,2-b]indoles as major products
      through a fully diastereoselective ABB'C four-component domino process that
      generates two cycles, three stereocenters, two C-C bonds, and two C-N bonds in a
      single operation.

PMID- 22392599
TI  - Leapfrog volume thresholds and perioperative complications after radical
      prostatectomy.
AB  - BACKGROUND: The authors explored the effect of Leapfrog volume thresholds (LVTs)
      on 5 short-term radical prostatectomy (RP) outcomes. METHODS: Within the Health
      Care Utilization Project Nationwide Inpatient Sample (NIS), the authors focused
      on RPs performed within the 7 most contemporary years (2001-2007). They tested
      rates of in-hospital mortality, intraoperative complications, postoperative
      complications, and blood transfusions as well as the mean length of stay (LOS),
      stratified according to the number of LVTs that were met. Multivariable
      regression analyses were adjusted further for potential confounders. RESULTS:
      Overall, 36.2%, 17.3%, 14.9%, 15.7%, 12.9%, and 3% of RPs were performed at
      institutions that reached 0 LVT, 1 LVT, 2 LVTs, 3 LVTs, 4 LVTs, and 5 LVTs,
      respectively. Relative to patients who underwent RP at institutions that reached
      0 LVTs, patients who underwent RP at institutions that reached 5 LVTs had fewer
      comorbidities, were younger, were more likely to hold private insurance, and were
      more likely to undergo concomitant pelvic lymphadenectomy (all P < .001). In
      multivariable analyses adjusted for hospital volume (HV), age, race, year of
      surgery, Charlson Comorbidity Index, hospital region and location, pelvic
      lymphadenectomy, and insurance status, LVT status was related inversely to LOS
      and the likelihood of receiving blood transfusions (both P < .001). CONCLUSIONS:
      The current results indicated that LVTs can provide a highly accurate prediction
      of the probability of 2 important, detrimental, short-term outcomes after RP,
      even after accounting for HV. The benefit at institutions that meet LVTs may
      exceed that at other institutions when short-term RP outcomes are considered.
      This observation should be taken into consideration when treatment decisions are
      made, especially because most RPs were performed at institutions that did not
      meet any LVTs.

PMID- 22392601
TI  - Quality disparities in child care for at-risk children: comparing Head Start and
      non-Head Start settings.
AB  - The study objectives are to describe child care type and quality experienced by
      developmentally at-risk children, examine quality differences between Head Start
      and non-Head Start settings, and identify factors associated with receiving
      higher-quality child care. Data are analyzed from the Early Childhood
      Longitudinal Survey, Birth Cohort, a prospective study of a nationally
      representative sample of US children born in 2001. The sample consisted of 7,500
      children who were assessed at 48 months of age. The outcome of interest is child
      care quality, measured by the Early Childhood Environmental Rating Scale (center
      care) and the Family Day Care Rating Scale (family day care). Results of
      descriptive and multivariate regression analyses are presented. Less than one
      third of poor children were in Head Start. Child care quality was higher in Head
      Start centers than other centers, particularly among poor children (4.75 vs.
      4.28, p < 0.001), Hispanics (4.90 vs. 4.45, p < 0.001), and whites (4.89 vs.
      4.51, p < 0.001). African Americans experienced the lowest quality care in both
      Head Start and non-Head Start centers. Quality disadvantage was associated with
      Head Start family care settings, especially for low birthweight children (2.04 in
      Head Start vs. 3.58 in non-Head Start, p < 0.001). Lower family day care quality
      was associated with less maternal education and African American and Hispanic
      ethnicity. Center-based Head Start provides higher quality child care for at-risk
      children, and expansion of these services will likely facilitate school readiness
      in these populations. Quality disadvantages in Head Start family day care
      settings are worrisome and warrant investigation.

PMID- 22392602
TI  - Prediction of preterm and low birth weight delivery by maternal periodontal
      parameters: receiver operating characteristic (ROC) curve analysis.
AB  - In this study we used receiver-operating characteristic (ROC) analysis to
      comparatively evaluate maternal periodontal parameters to predict preterm (PB)
      delivery and low birth weight (LBW) delivery among Jordanian women. A total of
      277 pregnant women (20 weeks of gestation or less) had periodontal examination at
      baseline and followed up until delivery. Gestational age and birth weight were
      retrieved from their medical records. ROC curve analyses were used to examine the
      overall discriminatory power of the studied periodontal parameters to predict PB,
      LBW, and PB or LBW. For the three outcome variables, the area under curve (AUC)
      ranged from 0.84 to 0.87 for average clinical attachment level (CAL), 0.78-0.86
      for percent of sites with CAL >= 5 mm, 0.63-0.74 for percent of sites with CAL >=
      6 mm, and 0.71-0.82 for number of missing teeth indicating that they had high
      discriminating power to predict adverse pregnancy outcomes. All other parameters
      had AUC less than 0.60 and thus had low discriminating power. Average CAL
      performed the best in predicting the studied adverse pregnancy outcomes because
      it has the highest AUC. The severity and extent of periodontal disease as
      measured by CAL can be used to predict the occurrence of adverse pregnancy
      outcomes.

PMID- 22392603
TI  - Comparison between once weekly, twice weekly, and daily oral iron therapy in
      Jordanian children suffering from iron deficiency anemia.
AB  - The efficacy of daily versus twice weekly and once weekly oral iron therapy was
      analyzed to optimize a protocol for treatment of IDM among Jordanian children.
      One hundred and forty-eight children aged between 6 and 60 months with Hb
      estimate less than 11 gm/dl were screened. They were randomly divided into three
      regimens of oral iron therapy for a period of 12 weeks; a group was supplemented
      with a single weekly dose of iron; a second group received two doses weekly; and
      a third group had a daily dose of iron. Hb was assayed 3 and 12 weeks after
      therapy, while ferritin was assayed after 12 weeks of treatment. A significant
      rise in Hb concentration was observed which was most significant 12 weeks after
      treatment. Iron supplementation after 3 weeks was similar in all treated groups,
      and no significant difference in Hb concentration among the three groups was
      noticed. By the end of the third week, the anemia had respectively resolved by
      18, 11.8 and 23.4% in the daily, twice weekly, and once weekly groups. On the
      other hand, the percentage of recovery of anemia respectively was 78, 90.2 and
      74.5% at the end of 12 weeks of iron therapy. Hb recovery percentage was
      comparable in the three treated groups, and no significant difference was
      reported between them either at 3 or at 12 weeks of therapy. Ferritin levels in
      the daily and twice weekly treated groups were similar after 12 weeks of iron
      therapy and were significantly higher than the ferritin levels of weekly treated
      group. Although the anemia in the three treated groups was resolved after 3 and
      12 weeks of oral iron therapy, we conclude that the regimen of two doses per week
      is the most effective in resolving anemia with less cost and fewer side effects.

PMID- 22392605
TI  - A new class of thermo- and solvatochromic metal-organic frameworks based on 4
      (pyridin-4-yl)benzoic acid.
AB  - Using 4-(pyridin-4-yl)benzoic acid, 44pba (1) as a ligand, two new metal
      coordination networks [Co(4)(44pba)(8)](n).[(DMF)(3).(EtOH)(0.25).(H(2)O)(4)](n)
      (2) and [Ni(4)(44pba)(8)](n).[(DMF)(3.5).(EtOH).(H(2)O)(1.5)](n) (3) were
      synthesized by solvothermal methods and structurally characterized. Compounds 2
      and 3 are isostructural but differ in their solvent content. Each is a 2D-network
      which forms a spiral parallel to [001], giving rise to three distinct large
      channels, accounting for some 47% of the unit cell volume. Both 2 and 3 display
      water-induced phase transformations with chromotropism, which has been confirmed
      by TGA and XRPD analysis. Solvatochromism in 2 is also evident with crystals
      exhibiting a range of colours depending on the solvent included. This phenomenon
      has been characterized using TGA, XRPD and UV-vis spectrophotometry.

PMID- 22392604
TI  - Compressed sensing reconstruction for whole-heart imaging with 3D radial
      trajectories: a graphics processing unit implementation.
AB  - A disadvantage of three-dimensional (3D) isotropic acquisition in whole-heart
      coronary MRI is the prolonged data acquisition time. Isotropic 3D radial
      trajectories allow undersampling of k-space data in all three spatial dimensions,
      enabling accelerated acquisition of the volumetric data. Compressed sensing (CS)
      reconstruction can provide further acceleration in the acquisition by removing
      the incoherent artifacts due to undersampling and improving the image quality.
      However, the heavy computational overhead of the CS reconstruction has been a
      limiting factor for its application. In this article, a parallelized
      implementation of an iterative CS reconstruction method for 3D radial
      acquisitions using a commercial graphics processing unit is presented. The
      execution time of the graphics processing unit-implemented CS reconstruction was
      compared with that of the C++ implementation, and the efficacy of the
      undersampled 3D radial acquisition with CS reconstruction was investigated in
      both phantom and whole-heart coronary data sets. Subsequently, the efficacy of CS
      in suppressing streaking artifacts in 3D whole-heart coronary MRI with 3D radial
      imaging and its convergence properties were studied. The CS reconstruction
      provides improved image quality (in terms of vessel sharpness and suppression of
      noise-like artifacts) compared with the conventional 3D gridding algorithm, and
      the graphics processing unit implementation greatly reduces the execution time of
      CS reconstruction yielding 34-54 times speed-up compared with C++ implementation.

PMID- 22392606
TI  - The health and social needs of older male prisoners.
AB  - OBJECTIVES: This study aimed to quantify the health and social needs of older
      male prisoners in the North West of England, to determine whether their needs
      were being met, and to explore an age cut-off for this group. METHODS: Data were
      collected by interview and case note review. Areas covered included physical
      health, mental health, personality disorder, cognitive impairment and social
      need. RESULTS: A total of 262 prisoners were included in the study. Over 90% had
      a physical health disorder, most commonly hypertension and osteoarthritis. A
      total of 61% had a mental disorder, most commonly major depressive disorder and
      alcohol misuse disorder. There were few differences within age bands for physical
      health problem or health/social need, but those aged 50-59 years had more mental
      disorder, including mental illness, substance misuse disorder and personality
      disorder. CONCLUSIONS: Older prisoners have a high level of health need and a
      different profile to the rest of the prison population. Fifty appears to be a
      useful age over which to define this group, and service provision should reflect
      this in a national management strategy.

PMID- 22392607
TI  - Spontaneous resolution of posterior ciliary artery occlusion.

PMID- 22392609
TI  - Successful management of extreme hypertriglyceridemia from pegaspargase with
      omega-3.

PMID- 22392608
TI  - A functional variant in FCRL3 is associated with higher Fc receptor-like 3
      expression on T cell subsets and rheumatoid arthritis disease activity.
AB  - OBJECTIVE: CD4+FoxP3+ Treg cells suppress effector T cells and prevent autoimmune
      disease. Treg cell function is deficient in active rheumatoid arthritis (RA), a
      loss which may play a role in the pathogenesis of this disease. We previously
      showed that a single-nucleotide polymorphism in the FCRL3 gene led to higher
      expression of Fc receptor-like 3 (FcRL3) on Treg cells and that FcRL3+ Treg cells
      are functionally deficient in comparison to FcRL3- Treg cells. This study was
      undertaken to investigate the potential role of FcRL3 in RA. METHODS: A cross
      sectional study was performed to evaluate the FCRL3 -169 genotype and FcRL3
      expression on T cell subsets, including Treg cells, in peripheral blood samples
      from 51 patients with RA enrolled in the University of California, San Francisco
      (UCSF) RA Cohort. Clinical data were obtained from the UCSF RA Cohort database.
      RESULTS: Patients with the FCRL3 -169C allele (genotype C/C or C/T) expressed
      higher levels of FcRL3 on Treg cells, and on CD8+ and gamma/delta T cells, in
      comparison to RA patients with the T/T genotype. Higher FcRL3 expression on these
      T cell subpopulations correlated with RA disease activity in patients harboring
      the FCRL3 -169C allele. Furthermore, FcRL3 expression on Treg cells was higher in
      patients with erosive RA, and the FCRL3 -169C allele was overrepresented in
      patients with erosive RA. CONCLUSION: Our findings indicate that FcRL3
      expression, which is strongly associated with the presence of the FCRL3 -169C
      allele, may serve as a biomarker for RA disease activity.

PMID- 22392610
TI  - Characterization of a putative thioredoxin peroxidase prx1 of Candida albicans.
AB  - In this study, we characterized a putative peroxidase Prx1 of Candida albicans
      by: 1) demonstrating the thioredoxin-linked peroxidase activity with purified
      proteins, 2) examining the sensitivity to several oxidants and the accumulation
      of intracellular reactive oxygen species with a null mutant (prx1Delta), a mutant
      (C69S) with a point mutation at Cys69, and a revertant, and 3) subcelluar
      localization. Enzymatic assays showed that Prx1 is a thioredoxin-linked
      peroxidase which reduces both hydrogen peroxide (H(2)O(2)) and tert-butyl
      hydroperoxide (t-BOOH). Compared with two other strong H(2)O(2) scavenger mutants
      for TSA1 and CAT1, prx1Delta and C69S were less sensitive to H(2)O(2), menadione
      and diamide at all concentrations tested, but were more sensitive to low
      concentration of t-BOOH. Intracellular reactive oxygen species accumulated in
      prx1Delta and C69S cells treated with t-BOOH but not H(2)O(2). These results
      suggest that peroxidase activity of Prx1 is specified to t-BOOH in cells. In both
      biochemical and physiological cases, the evolutionarily conserved Cys69 was found
      to be essential for the function. Immunocytochemical staining revealed Prx1 is
      localized in the cytosol of yeast cells, but is translocated to the nucleus
      during the hyphal transition, though the significances of this observation are
      unclear. Our data suggest that PRX1 has a thioredoxin peroxidase activity
      reducing both t-BOOH and H(2)O(2), but its cellular function is specified to t
      BOOH.

PMID- 22392611
TI  - Treatment of acute ischemic stroke with clot retrieval devices.
AB  - OPINION STATEMENT: Mechanical clot retrieval is increasingly used for flow
      restoration and thrombectomy in acute embolic stroke. Emerging as a treatment
      option in addition to intravenous or intra-arterial thrombolysis, it is currently
      being further developed and investigated as a potential first-line and stand
      alone treatment. The ability to rapidly restore flow and effectively retrieve
      clots from large intracranial arteries is reflected by angiographic data and
      preliminary clinical results. This article reviews the principles and technical
      aspects of this new technique, its emergence from the spectrum of intravenous and
      endovascular stroke treatment, and summarizes the first clinical results for
      acute ischemic anterior and posterior circulation stroke. Clot retrieval devices
      are a very promising option for treatment of acute ischemic stroke in the setting
      of large vessel occlusion. However, there currently exists a reported discrepancy
      between excellent recanalization rates and less satisfactory clinical outcomes.
      This problem urgently needs to be addressed in a prospective randomized fashion
      and improvements of treatment be recognized and implemented before clot retrieval
      can be considered an established form of acute stroke treatment.

PMID- 22392612
TI  - Hemoglobinopathies and stroke: strategies for prevention and treatment.
AB  - OPINION STATEMENT: Current treatment options for stroke in sickle cell disease
      (SCD) and thalassemia are limited. Hypercoagulation occurs in both diseases
      partly due to activated platelets and red blood cell dysmorphology and
      dysfunction, resulting in chronic anemia. This overlapping pathophysiology of the
      nervous system promotes the role of some common treatment modalities for these
      similar diseases. The current evidence suggests that chronic exchange transfusion
      and stem cell transplantation/bone marrow transplant (BMT) can be used in both
      diseases. Exchange transfusion is the mainstay of therapy of acute stroke in SCD
      whereas blood transfusions and hydroxyurea appear to be the most effective
      current treatments. However, evidence suggests that exchange transfusion should
      be initiated in acute ischemic stroke (AIS) and chronic transfusion continued in
      both diseases after AIS. Exchange transfusion can also be used acutely in AIS
      with thalassemia as this disorder is also associated with hypervolemia at
      baseline, occurring secondary to chronic anemia. The ideal length of chronic
      transfusions for both primary and secondary stroke prevention still needs to be
      better defined. Stem cell transplant or BMT is the only curative treatment for
      both diseases. However, timing needs to be further investigated. If
      transplantation is effective, it may need to be done before the child with SCD
      expresses disease, such as in infancy. However, in infancy, we cannot predict the
      severity of the phenotype in SCD with certainty, so an individual decision about
      transplantation is difficult to make. In thalassemia, transplantation may be
      effective later because vasculopathy is not the problem as in SCD. Furthermore,
      cerebrovascular disease occurs later in thalassemia than in SCD. Finally, aspirin
      is a treatment modality that also warrants further investigation. There are
      limited studies on the effectiveness of aspirin in SCD and thalassemias. Few
      studies have demonstrated clinical improvement of stroke in patients with
      hemoglobinopathies. Given the successful use of aspirin in the treatment and
      prevention of recurrent cardioembolic events in patients without
      hemoglobinopathies, diseases with hypercoagulability, such as SCD and
      thalassemia, may also benefit from the use of aspirin for treatment and
      prevention. However, the evidence available is based on case and retrospective
      studies, necessitating future larger and more valid studies to evaluate safety
      and effectiveness.

PMID- 22392613
TI  - Assessment of health risk associated with persistent organic pollutants in water.
AB  - This paper presents the results of analyses of water samples taken from water
      intakes supplying one of the districts located near the city of Wroclaw.
      Surprisingly high concentrations of polychlorinated biphenyls and chloroorganic
      pesticides, classified as persistent organic pollutants (POPs), were detected in
      the monitored sites. Basing on the analytical and toxicological data, the
      individual health risks related to carcinogenic effects (excess cancer risk over
      a lifetime) in humans were assessed, resulting from direct ingestion of community
      water. Also noncarcinogenic effects resulting from exposure to the examined POPs
      were determined. The conservative approach to risk assessment, taking into
      account a safety margin for data incompleteness, was adopted. The carcinogenic
      risk was found to slightly exceed the unconditionally acceptable risk of 10(-6)
      in the case of polychlorinated biphenyls and hexachlorocyclohexane, for all the
      inhabitant populations. The determined values of noncarcinogenic effects
      expressed by hazard quotient and hazard index indicate that the water pollutants
      and their concentrations do not cause an increase in noncarcinogenic incidences
      in the inhabitants using the monitored water sources.

PMID- 22392614
TI  - New kinetic-spectrophotometric method for monitoring the concentration of iodine
      in river and city water samples.
AB  - A new kinetic method has been developed for the determination of iodine in water
      samples. The method is based on the catalytic effect of I(-) with the oxidation
      of Indigo Carmine (IC) by KBrO(3) in the sulfuric acid medium. The optimum
      conditions obtained are 0.16 M sulfuric acid, 1 * 10(-3) M of IC, 1 * 10(-2) M
      KBrO(3), reaction temperature of 35 degrees C, and reaction time of 80 s at 612
      nm. Under the optimized conditions, the method allowed the quantification of I(-)
      in a range of 12-375 ng/mL with a detection limit of 0.46 ng/mL. The method was
      applied to the determination of iodine in river and city water samples with the
      satisfactorily results.

PMID- 22392615
TI  - Beryllium natural background concentration and mobility: a reappraisal examining
      the case of high Be-bearing pyroclastic rocks.
AB  - Beryllium is widely distributed in soils at low levels, but it can also occur
      naturally in higher concentrations in a variety of materials exploited for many
      industrial applications. Beryllium is also one of the most toxic natural elements
      and is known to be a human carcinogen. A concise account of the literature data
      on baseline concentrations of Be in soils illustrates the possibility of
      worldwide presence of areas with a high natural background concentration of Be
      (up to 300 mg/kg), the crustal abundance of which is generally estimated to be in
      the range 2-6 mg/kg. Nevertheless, the number of available data is rather limited
      in comparison with those about other toxic elements such as Pb, Cd and Cr. This
      has probably caused the choice of low values of concentration level as the
      reference for the definition of soil contamination: these values are not always
      realistic and are not applicable to large areas. As a case study, we report and
      analyse a diffuse, unusually high (up to 80 mg/kg, average approximately 20
      mg/kg), natural occurrence of beryllium in loose and poorly consolidated
      pyroclastic layers related to the Pleistocene activity of the Vico volcano.
      Additionally, the analysis of Be leachability has been carried out, providing
      evidence of a not negligible mobility in contrast with the scarce data presented
      in the literature that usually indicate beryllium as an element with low mobility
      in oxidising surface environmental conditions. This research marks the beginning
      of a possible reappraisal of beryllium geochemical behaviour and background
      levels, providing more realistic reference values for risk assessment and land
      management.

PMID- 22392616
TI  - Fast simultaneous determination of traces of Cu(II) and Co(II) in soils and
      sediments with the luminol/perborate chemiluminescent system.
AB  - A flow injection analysis method based on ion chromatography and luminol
      chemiluminescence detection was used for the simultaneous determination of copper
      (II) and cobalt (II) trace levels in soils and sediments following microwave
      assisted acid digestion. Detection was based on chemiluminescence (CL) of the
      luminol-perborate system in an alkaline medium, which is catalyzed by both
      transition metals. The concentration and pH of the eluent (oxalic acid) was found
      to affect CL intensities and retention times, both of which were inversely
      proportional to the oxalic acid concentration. The calibration curves for both
      metal ions were linear and allowed a limit of detection of 0.003 MUg l(-1) for
      cobalt (II) and 0.014 MUg l(-1) for cooper (II) to be calculated. The proposed
      method was successfully used to determine both metal ions in certified reference
      materials of stream and river sediments and soil samples. Based on the results,
      the determination is free of interferences from the usual concomitant ions.

PMID- 22392617
TI  - The effect of changes in land use on nitrate concentration in water supply wells
      in southern Chester County, Pennsylvania.
AB  - An analysis of private potable water well data was conducted for seven single
      family residential developments in southern Chester County, Pennsylvania.
      Background data were available for 165 wells within the communities when the
      wells were first drilled in the 1980s and early 1990s. Sampling of 75 wells
      within these same communities was performed in 2006 to determine whether
      conversion of the land to residential housing along with the use of conventional
      on-lot septic systems had resulted in elevated concentration of nitrate-nitrogen
      in the drinking water aquifer. The data indicate that prior land use influenced
      the occurrence of nitrate-nitrogen in the drinking water aquifer. The median
      nitrate-nitrogen concentration for the 165 wells in the background dataset was
      2.9 mg/L. One hundred-seven of those wells were drilled on land previously used
      for active agricultural purposes. The median nitrate concentration in these wells
      was 3.8 mg/L. Of 48 wells drilled on forested land, the median nitrate
      concentration was 1.1 mg/L, approximately 3.5 times lower than those drilled on
      active agricultural land. The median nitrate concentration in the 2006 sampling
      dataset was 3.6 mg/L, an increase of 0.7 mg/L. The data indicate that conversion
      of the land has not resulted in contamination of the drinking water aquifer with
      respect to nitrate-nitrogen. Likewise, the data suggest that the conversion has
      not resulted in significant improvements to overall water quality.

PMID- 22392618
TI  - Statistical apportionment and risk assessment of selected metals in sediments
      from Rawal Lake (Pakistan).
AB  - The present study was carried out in order to evaluate the statistical
      apportionment and risk assessment of selected metals (Ca, Cd, Co, Cr, Cu, Fe, K,
      Li, Mg, Mn, Na, Pb, Sr, and Zn) in freshly deposited sediments in Rawal Lake,
      Pakistan. Composite sediment samples were collected, oven-dried, grounded,
      homogenized, and processed to assess the water-soluble and acid extractable
      concentrations of the metals in the water extract and acid extract of the
      sediments using flame atomic absorption spectrophotometer. Statistical methods
      were used to identify the possible sources of the metals. Sediment quality
      guidelines and potential acute toxicity were used to evaluate the
      ecotoxicological sense of selected metals. Non-carcinogenic health risk
      assessment was also carried out to determine the potential adverse health risks
      to the inhabitants. Relatively higher concentration was noted for Ca, Fe, Mg, Na,
      K, Mn, and Sr in the sediment samples. Principal component analysis and cluster
      analysis revealed anthropogenic contributions of Cd, Pb, Cr, Mn, Fe, and Li in
      the sediments. Enrichment factors of the metals in sediments showed severe to
      moderate enrichment of Cd, Pb, Ca, Fe, Li, Mn, and Sr. Geoaccumulation indices
      and contamination factors evidenced significant contamination by Cd and Pb,
      although, on the whole, low degree of contamination was noted. The levels of some
      metals exceeded the sediment quality guidelines, which revealed frequently
      adverse biological effects to the dwelling biota in the aquatic ecosystem. The
      sediments were found to be significantly contaminated by Cd, Pb, Cr, Mn, Fe, and
      Li.

PMID- 22392619
TI  - Toxicity of sediment pore water in Puget Sound (Washington, USA): a review of
      spatial status and temporal trends.
AB  - Data from toxicity tests of the pore water extracted from Puget Sound sediments
      were compiled from surveys conducted from 1997 to 2009. Tests were performed on
      664 samples collected throughout all of the eight monitoring regions in the
      Sound, an area encompassing 2,294.1 km(2). Tests were performed with the gametes
      of the Pacific purple sea urchin, Strongylocentrotus purpuratus, to measure
      percent fertilization success as an indicator of relative sediment quality. Data
      were evaluated to determine the incidence, degree of response, geographic
      patterns, spatial extent, and temporal changes in toxicity. This is the first
      survey of this kind and magnitude in Puget Sound. In the initial round of surveys
      of the eight regions, 40 of 381 samples were toxic for an incidence of 10.5 %.
      Stations classified as toxic represented an estimated total of 107.1 km(2),
      equivalent to 4.7 % of the total area. Percent sea urchin fertilization ranged
      from >100 % of the nontoxic, negative controls to 0 %. Toxicity was most
      prevalent and pervasive in the industrialized harbors and lowest in the deep
      basins. Conditions were intermediate in deep-water passages, urban bays, and
      rural bays. A second round of testing in four regions and three selected urban
      bays was completed 5-10 years following the first round. The incidence and
      spatial extent of toxicity decreased in two of the regions and two of the bays
      and increased in the other two regions and the third bay; however, only the
      latter change was statistically significant. Both the incidence and spatial
      extent of toxicity were lower in the Sound than in most other US estuaries and
      marine bays.

PMID- 22392620
TI  - Simultaneous screening of glutathione and cyanide adducts using precursor ion and
      neutral loss scans-dependent product ion spectral acquisition and data mining
      tools.
AB  - Drugs can be metabolically activated to soft and hard electrophiles, which are
      readily trapped by glutathione (GSH) and cyanide (CN), respectively. These
      adducts are often detected and structurally characterized using separate tandem
      mass spectrometry methods. We describe a new method for simultaneous screening of
      GSH and CN adducts using precursor ion (PI) and neutral loss (NL) scans-dependent
      product ion spectral acquisition and data mining tools on an triple quadrupole
      linear ion trap mass spectrometry. GSH, potassium cyanide, and their stable
      isotope labeled analogues were incubated with liver microsomes and a test
      compound. Negative PI scan of m/z 272 for detection of GSH adducts and positive
      NL scans of 27 and 29 Da for detection of CN adducts were conducted as survey
      scans to trigger acquisition of enhanced resolution (ER) spectrum and subsequent
      enhanced product ion (EPI) spectrum. Post-acquisition data mining of EPI data set
      using NL filters of 129 and 27 Da was then performed to reveal the GSH adducts
      and CN adducts, respectively. Isotope patterns and EPI spectra of the detected
      adducts were utilized for identification of their molecular weights and
      structures. The effectiveness of this method was evaluated by analyzing reactive
      metabolites of nefazodone formed from rat liver microsomes. In addition to known
      GSH- and CN-trapped reactive metabolites, several new CN adducts of nefazodone
      were identified. The results suggested that current approach is highly effective
      in the analysis of both soft and hard reactive metabolites and can be used as a
      high-throughput method in drug discovery.

PMID- 22392621
TI  - Surface assisted laser desorption ionization-mass spectrometry (SALDI-MS) for
      analysis of polyester degradation products.
AB  - Novel surface assisted laser desorption ionization-mass spectrometry (SALDI-MS)
      method was developed for rapid analysis of low molecular mass polyesters and
      their degradation products by laser desorption ionization-mass spectrometry.
      Three polycaprolactone materials were analyzed by the developed method before and
      after hydrolytic degradation. The signal-to-noise values obtained by SALDI-MS
      were 20-100 times higher compared with the ones obtained by using traditional
      MALDI-MS matrices. A clean background at low mass range and higher resolution was
      obtained by SALDI-MS. Different nanoparticle, cationizing agent, and solvent
      combinations were evaluated. Halloysite nanoclay and magnesium hydroxide showed
      the best potential as SALDI surfaces. The SALDI-MS spectrum of the polyester
      hydrolysis products was verified by ESI-MS. The developed SALDI-MS method
      possesses several advantages over existing methods for similar analyses.

PMID- 22392624
TI  - The statistical challenges in clinical studies. Preface.

PMID- 22392622
TI  - Data processing for 3D mass spectrometry imaging.
AB  - Data processing for three dimensional mass spectrometry (3D-MS) imaging was
      investigated, starting with a consideration of the challenges in its practical
      implementation using a series of sections of a tissue volume. The technical
      issues related to data reduction, 2D imaging data alignment, 3D visualization,
      and statistical data analysis were identified. Software solutions for these tasks
      were developed using functions in MATLAB. Peak detection and peak alignment were
      applied to reduce the data size, while retaining the mass accuracy. The main
      morphologic features of tissue sections were extracted using a classification
      method for data alignment. Data insertion was performed to construct a 3D data
      set with spectral information that can be used for generating 3D views and for
      data analysis. The imaging data previously obtained for a mouse brain using
      desorption electrospray ionization mass spectrometry (DESI-MS) imaging have been
      used to test and demonstrate the new methodology.

PMID- 22392625
TI  - Photocatalytic activity enhancement in doped titanium dioxide by crystal defects.
AB  - Visible light sensitive Fe(3+) and Ce(4+) co-doped nano TiO(2) photocatalyst has
      been prepared by a modified aqueous sol-gel method and the activity has been
      measured in terms of degradation of MB dye. Both dopants shifted the absorption
      profile of TiO(2) to the visible region and improved activity. Fe(3+) ions
      trapped the charge carriers due to the stable electronic configuration and
      improved their separation. Ce(4+) ions, which were mainly located at the grain
      boundaries, cause dislocations by bending the valence and conduction bands of
      TiO(2) and prevent the recombination of photoexcited electrons and holes. The co
      doped TiO(2) compositions exhibited higher photocatalytic activity than that of
      pure titania and commercially available Degussa P25 under visible light by
      utilising the individual and synergistic contributions of Fe(3+) and Ce(4+)
      dopants, respectively.

PMID- 22392626
TI  - Analysis of two strains of Peanut stunt virus: satRNA-associated and satRNA free.
AB  - Peanut stunt virus (PSV) is a pathogen of legumes, vegetables, trees, and weeds
      occurring worldwide. The species is characterized by significant genetic
      variability. PSV strains are classified into four subgroups on the basis of their
      nucleotide sequence homology. Here, we are presenting two further, fully
      sequenced PSV strains-PSV-Ag and PSV-G, that could be considered as I subgroup
      representatives. However, their sequence homology with other typical I subgroups
      members, similarly as another strain-PSV-P, characterized by our group
      previously, is lower than 90%. This lead us to propose further subdivision of the
      I subgroup into IA, IB, and IC units, and to classify PSV-Ag and PSV-G strains to
      the last one. In this article, we are showing that identity level of PSV-Ag and
      PSV-G is very high and apart from the presence of satRNA in the first one, they
      differ only by a few nucleotides in their genomic RNAs. Nevertheless, symptoms
      they cause on host plants might differ significantly, just as the levels in
      infected plants. Effect of single amino acid changes between strains on the three
      dimensional structure of viral proteins was analyzed. Differences occur mainly on
      the protein surfaces which can possibly affect protein-protein interaction in
      infected cells, which is discussed.

PMID- 22392627
TI  - The effects of lobeline and naltrexone on methamphetamine-induced place
      preference and striatal dopamine and serotonin levels in adolescent rats with a
      history of maternal separation.
AB  - Exposure to early life stress has been suggested to increase an individual's
      vulnerability to methamphetamine (MA) dependence. Although there is no cure for
      drug dependence, the opioid and vesicular monoamine transporter 2 (VMAT2) systems
      may be useful targets for treatment insofar as they play pivotal roles in the
      neurochemistry of addiction. Here we investigated the effects of naltrexone
      (opioid antagonist) and lobeline (VMAT2 inhibitor) on MA-induced place preference
      in adolescent rodents subjected to early life trauma (maternal separation, MS)
      and controls, as well as the effects on dopamine and serotonin levels in the
      striatum. We found: (1) maternal separation attenuated methamphetamine-induced
      place preference; (2) lobeline and naltrexone treatment had differential effects
      on serotonin and dopamine concentrations in the striatum, naltrexone increased
      serotonin levels in the maternally separated animals. The hypothesized effect of
      early adversity increasing MA-induced place preference may not be apparent in
      adolescence. However the data are consistent with the hypothesis that early life
      stress influences neurochemical pathways that predispose an individual to drug
      dependence.

PMID- 22392628
TI  - Gilt required for RTL550-CYS-MOG to treat experimental autoimmune
      encephalomyelitis.
AB  - MHC class II-derived recombinant T cell receptor ligands (RTLs) modulate the
      behavior of pathogenic T cells and can reverse clinical and histological signs of
      autoimmune disease in experimental autoimmune encephalomyelitis (EAE),
      experimental autoimmune uveitis (EAU) and collagen-induced arthritis (CIA), and
      are currently in clinical trials for treatment of multiple sclerosis (MS). To
      expand the utility of these rationally-designed biologics and explore their
      mechanism(s) of activity in vivo, we have engineered RTL constructs bearing
      cysteine-tethered antigenic peptides and demonstrate that the appropriate
      cysteine-tethered RTLs effectively treat EAE. The data presented here suggests
      that the mechanism by which antigen-specific tolerance induction by RTLs bearing
      cysteine-tethered antigenic peptides in vivo involves delivery of RTL/antigen to
      endosomal compartments for processing and re-presentation by full-length MHC
      class II, with RTLs bearing cysteine-tethered antigenic peptides requiring gamma
      interferon-inducible lysosomal thiol-reductase (GILT) for therapeutic activity.

PMID- 22392629
TI  - Patient navigation for breast and colorectal cancer in 3 community hospital
      settings: an economic evaluation.
AB  - BACKGROUND: The Ralph Lauren Cancer Center implemented patient navigation
      programs in sites across the United States building on the model pioneered by
      Harold P. Freeman, MD. Patient navigation targets medically underserved with the
      objective of reducing the time interval between an abnormal cancer finding,
      diagnostic resolution, and treatment initiation. In this study, the authors
      assessed the incremental cost effectiveness of adding patient navigation to
      standard cancer care in 3 community hospitals in the United States. METHODS: A
      decision-analytic model was used to assess the cost effectiveness of a colorectal
      and breast cancer patient navigation program over the period of 1 year compared
      with standard care. Data sources included published estimates in the literature
      and primary costs, aggregate patient demographics, and outcome data from 3
      patient navigation programs. RESULTS: After 1 year, compared with standard care
      alone, it was estimated that offering patient navigation with standard care would
      allow an additional 78 of 959 individuals with an abnormal breast cancer
      screening and an additional 21 of 411 individuals with abnormal colonoscopies to
      reach timely diagnostic resolution. Without including medical treatment costs
      saved, the cost-effectiveness ratio ranged from $511 to $2080 per breast cancer
      diagnostic resolution achieved and from $1192 to $9708 per colorectal cancer
      diagnostic resolution achieved. CONCLUSIONS: The current results indicated that
      implementing breast or colorectal cancer patient navigation in community hospital
      settings in which low-income populations are served may be a cost-effective
      addition to standard cancer care in the United States.

PMID- 22392630
TI  - A supramolecular polymer blend containing two different supramolecular polymers
      through self-sorting organization of two heteroditopic monomers.

PMID- 22392631
TI  - Crosstalk between oligodendrocytes and cerebral endothelium contributes to
      vascular remodeling after white matter injury.
AB  - After stroke and brain injury, cortical gray matter recovery involves mechanisms
      of neurovascular matrix remodeling. In white matter, however, the mechanisms of
      recovery remain unclear. In this study, we demonstrate that oligodendrocytes
      secrete matrix metalloproteinase-9 (MMP-9), which accelerates the angiogenic
      response after white matter injury. In primary oligodendrocyte cultures,
      treatment with the proinflammatory cytokine interleukin-1beta (IL-1beta) induced
      an upregulation and secretion of MMP-9. Conditioned media from IL-1beta
      stimulated oligodendrocytes significantly amplified matrigel tube formation in
      brain endothelial cells, indicating that MMP-9 from oligodendrocytes can promote
      angiogenesis in vitro. Next, we asked whether similar signals and substrates
      operate after white matter injury in vivo. Focal white matter injury and
      demyelination was induced in mice via stereotactic injection of
      lysophosphatidylcholine into corpus callosum. Western blot analysis showed that
      IL-1beta expression was increased in damaged white matter. Immunostaining
      demonstrated MMP-9 signals in myelin-associated oligodendrocytic basic protein
      positive oligodendrocytes. Treatment with an IL-1beta-neutralizing antibody
      suppressed the MMP-9 response in oligodendrocytes. Finally, we confirmed that the
      broad spectrum MMP inhibitor GM6001 inhibited angiogenesis around the injury area
      in this white matter injury model. In gray matter, a neurovascular niche promotes
      cortical recovery after brain injury. Our study suggests that an analogous
      oligovascular niche may mediate recovery in white matter.

PMID- 22392632
TI  - Multifunctional T cell reactivity with native and glycosylated type II collagen
      in rheumatoid arthritis.
AB  - OBJECTIVE: Type II collagen (CII) is a cartilage-specific protein to which a loss
      of immune tolerance may trigger autoimmune reactions and cause arthritis. The
      major T cell epitope on CII, amino acids 259-273, can be presented by several HLA
      DRB1 04 alleles in its native or posttranslational glycosylated form. The present
      study was undertaken to functionally explore and compare CII-autoreactive T cells
      from blood and synovial fluid of patients with rheumatoid arthritis (RA).
      METHODS: Peripheral blood was obtained from HLA-DRB1 04-positive RA patients (n =
      10) and control subjects (n = 10) and stimulated in vitro with several variants
      of the CII(259-273) epitope, i.e., unmodified, glycosylated on Lys-264,
      glycosylated on Lys-270, or glycosylated on both Lys-264 and Lys-270. Up
      regulation of CD154 was used to identify responding T cells. These cells were
      further characterized by intracellular staining for interleukin-17 (IL-17),
      interferon-gamma (IFNgamma), and IL-2 by flow cytometry. Synovial T cells from RA
      patients were investigated in parallel. RESULTS: Multifunctional T cell responses
      toward all examined variants of the CII(259-273) peptide could be detected in RA
      patients and, to a lesser extent, also in healthy HLA-matched controls (P <
      0.001). In RA patients, a comparison between blood- and joint-derived T cell
      function revealed a significant increase in levels of the proinflammatory
      cytokine IFNgamma in synovial T cells (P = 0.027). Studies of longitudinally
      obtained samples showed that T cell responses were sustained over the course of
      disease, and even included epitope spreading. CONCLUSION: The identification of
      inflammatory T cell responses to both glycosylated and nonglycosylated variants
      of the major CII epitope in RA patients suggests that CII autoreactivity in RA
      may be more common than previously recognized.

PMID- 22392633
TI  - Lung ventilation- and perfusion-weighted Fourier decomposition magnetic resonance
      imaging: in vivo validation with hyperpolarized 3He and dynamic contrast-enhanced
      MRI.
AB  - The purpose of this work was to validate ventilation-weighted (VW) and perfusion
      weighted (QW) Fourier decomposition (FD) magnetic resonance imaging (MRI) with
      hyperpolarized (3)He MRI and dynamic contrast-enhanced perfusion (DCE) MRI in a
      controlled animal experiment. Three healthy pigs were studied on 1.5-T MR
      scanner. For FD MRI, the VW and QW images were obtained by postprocessing of time
      resolved lung image sets. DCE acquisitions were performed immediately after
      contrast agent injection. (3)He MRI data were acquired following the
      administration of hyperpolarized helium and nitrogen mixture. After baseline MR
      scans, pulmonary embolism was artificially produced. FD MRI and DCE MRI perfusion
      measurements were repeated. Subsequently, atelectasis and air trapping were
      induced, which followed with FD MRI and (3)He MRI ventilation measurements.
      Distributions of signal intensities in healthy and pathologic lung tissue were
      compared by statistical analysis. Images acquired using FD, (3)He, and DCE MRI in
      all animals before the interventional procedure showed homogeneous ventilation
      and perfusion. Functional defects were detected by all MRI techniques at
      identical anatomical locations. Signal intensity in VW and QW images was
      significantly lower in pathological than in healthy lung parenchyma. The study
      has shown usefulness of FD MRI as an alternative, noninvasive, and easily
      implementable technique for the assessment of acute changes in lung function.

PMID- 22392634
TI  - Enhanced epifluorescence microscopy by uniform and intensity optimized
      illumination.

PMID- 22392635
TI  - Inhibition of natural killer cells protects the liver against acute injury in the
      absence of glycine N-methyltransferase.
AB  - Glycine N-methyltransferase (GNMT) catabolizes S-adenosylmethionine (SAMe), the
      main methyl donor of the body. Patients with cirrhosis show attenuated GNMT
      expression, which is absent in hepatocellular carcinoma (HCC) samples. GNMT(-/-)
      mice develop spontaneous steatosis that progresses to steatohepatitis, cirrhosis,
      and HCC. The liver is highly enriched with innate immune cells and plays a key
      role in the body's host defense and in the regulation of inflammation. Chronic
      inflammation is the major hallmark of nonalcoholic steatohepatitis (NASH)
      progression. The aim of our study was to uncover the molecular mechanisms leading
      to liver chronic inflammation in the absence of GNMT, focusing on the implication
      of natural killer (NK) / natural killer T (NKT) cells. We found increased
      expression of T helper (Th)1- over Th2-related cytokines, tumor necrosis factor
      (TNF)-related apoptosis-inducing ligand (TRAIL)-R2/DR5, and several ligands of NK
      cells in GNMT(-/-) livers. Interestingly, NK cells from GNMT(-/-) mice were
      spontaneously activated, expressed more TRAIL, and had strong cytotoxic activity,
      suggesting their contribution to the proinflammatory environment in the liver.
      Accordingly, NK cells mediated hypersensitivity to concanavalin A (ConA)-mediated
      hepatitis in GNMT(-/-) mice. Moreover, GNMT(-/-) mice were hypersensitive to
      endotoxin-mediated liver injury. NK cell depletion and adoptive transfer of
      TRAIL(-/-) liver-NK cells protected the liver against lipopolysaccharide (LPS)
      liver damage. CONCLUSION: Our data allow us to conclude that TRAIL-producing NK
      cells actively contribute to promote a proinflammatory environment at early
      stages of fatty liver disease, suggesting that this cell compartment may
      contribute to the progression of NASH.

PMID- 22392636
TI  - Cerebrospinal fluid volume replacement following large endoscopic anterior
      cranial base resection.
AB  - BACKGROUND: Large endoscopic skull-base resections often result in extensive
      postoperative pneumocephalus secondary to copious evacuation of cerebrospinal
      fluid (CSF) during the procedures. Replacing CSF lost during craniotomy with
      saline is a common technique in neurosurgery, but is difficult after extensive
      transnasal resection of the anterior cranial base because direct transnasal CSF
      augmentation will escape until the skull base reconstruction is sealed. The
      present study evaluated the effectiveness of intraoperative CSF volume
      replacement via lumbar drains on improving postoperative outcomes. METHODS: Ten
      large endoscopic anterior skull-base resections (>2.5 cm) were performed from
      2008 to 2011. Sellar, parasellar, and transplanum resections were excluded.
      Etiologies included esthesioneuroblastoma (2), squamous cell carcinoma (2),
      intracranial dermoid (2), adenocarcinoma (1), adenoid cystic carcinoma (1),
      melanoma (1), and meningioma (1). Six patients were administered preservative
      free normal saline via lumbar drain during skull-base reconstruction. Data
      collected included volume of postoperative pneumocephalus, intravenous pain
      medicine requirements 24 hours after surgery, and length of hospital stay.
      RESULTS: Volume of pneumocephalus (4.78 cm vs 12.8 cm(3) , p = 0.04) and length
      of hospital stay (2.17 days vs 8.5 days, p = 0.03) were significantly decreased
      in the normal saline volume replacement group. Average intravenous pain
      medication requirements were reduced in the first 24 hours postoperatively (8 mg
      morphine vs 14 mg morphine, p = 0.25), but did not reach statistical
      significance. CONCLUSION: Evacuation of intracranial air by transthecal
      administration of saline during reconstruction of large anterior cranial base
      defects was an effective technique to decrease postoperative pneumocephalus and
      length of hospital stay. Further evaluation is warranted.

PMID- 22392637
TI  - Lipolytic proteomics.
AB  - Activity-based proteomics (ABP) employs small molecular probes to specifically
      label sets of enzymes based on their shared catalytic mechanism. Given that the
      vast majority of lipases belong to the family of serine hydrolases and share a
      nucleophilic active-site serine as part of a catalytic triad, activity-based
      probes are ideal tools to study lipases and lipolysis. Moreover, the ability of
      ABP to highlight or isolate specific subproteomes results in a massive decrease
      of sample complexity. Thereby, in-depth analysis of enzymes of interest with mass
      spectrometry becomes feasible. In this review, we cover probe design,
      technological developments, and applications of ABP of lipases, as well as give
      an overview of relevant identified proteins.

PMID- 22392638
TI  - Suffering, frustration, and anger: class, gender and history in Sri Lankan
      suicide stories.
AB  - This paper explores competing stories of suffering, frustration and anger that
      shape the performance and reception of suicidal behaviours in contemporary Sri
      Lanka. Drawing from the results of 21 months of ethnographic fieldwork, I show
      how suicidal acts fit within broader narratives of class and gender experience
      and expression that draw from contemporary and historical 'folk' and 'state'
      discourses. Debates over whether suffering, frustration and anger are legitimate
      socio-effective states to exhibit come to determine the kinds of claims and
      counter-claims that suicidal people on the one hand, and those charged with their
      treatment and management on the other, can make with regard to the efficacy of
      suicide as a means of social action. Through such debates-not only what it means
      to be suicidal in Sri Lanka but also what it means to be middle class or working
      class, male or female, etc. are made and remade anew.

PMID- 22392639
TI  - Postcolonial suicide among Inuit in Arctic Canada.
AB  - Indigenous youth suicide incidence is high globally, and mostly involves young
      males. However, the Inuit of Arctic Canada have a suicide rate that is among the
      highest in the world (and ten times that for the rest of Canada). The author
      suggests that suicide increase has emerged because of changes stemming in part
      from the Canadian government era in the Arctic in the 1950s and 1960s. The
      effects of government intervention dramatically affected kin relations, roles,
      and responsibilities, and affinal/romantic relationships. Suicide is embedded in
      these relationships. The author also discusses the polarization between
      psychiatric and indigenous/community methods of healing, demonstrating that
      government-based intervention approaches to mental health are not working well,
      and traditional cultural healing practices often take place outside of the
      mainstream clinics in these communities. The main questions of the paper are: Who
      should control suicide prevention? What is the best knowledge base for suicide
      prevention?

PMID- 22392640
TI  - Exo-functionalized shape-persistent [2+3] cage compounds: influence of molecular
      rigidity on formation and permanent porosity.

PMID- 22392641
TI  - Flat-top illumination profile in an epifluorescence microscope by dual microlens
      arrays.
AB  - Low uniformity in illumination across the image plane impairs the ability of a
      traditional epifluorescence microscope to quantify fluorescence intensities. Two
      microlens arrays (MLAs) were introduced into the illumination path of two
      different epifluorescence microscope systems to improve the uniformity of the
      illumination. Measurements of the uniformity of illumination were performed with
      a CCD camera in the focal plane and with fluorescent beads in the image plane. In
      semi critical alignment, a uniformity of illumination of 15-23% was found
      compared with 1-2% in the modified system. Coefficient of variation (CV) of
      fluorescent beads measured on the unmodified system was 20.4% +/- 5.3% in semi
      critical alignment and 10.8% +/- 1.3% in Koehler alignment. On the MLA systems,
      CV was 7.9% +/- 2.0% and on a flow cytometer, the CV was 6.7% +/- 0.7%.
      Implementation of MLAs in an epifluorescence microscope improves the uniformity
      of illumination, thereby reducing the variation in detection of fluorescent
      signals of the measured objects and becomes equivalent to that of flow cytometry.

PMID- 22392642
TI  - Validity of simplified 3'-deoxy-3'-[18F]fluorothymidine uptake measures for
      monitoring response to chemotherapy in locally advanced breast cancer.
AB  - PURPOSE: Positron emission tomography using 3'-deoxy-3'-[(18)F]fluorothymidine
      ([(18)F]FLT) has been suggested as a means for monitoring response to
      chemotherapy. The aim of this study was to evaluate the validity of simplified
      uptake measures for assessing response to chemotherapy using [(18)F]FLT in
      locally advanced breast cancer (LABC). PROCEDURES: Fifteen LABC patients
      underwent dynamic [(18)F]FLT scans both prior to and after the first cycle of
      chemotherapy with fluorouracil, epirubicin or doxorubicin, and cyclophosphamide.
      The net uptake rate constant of [(18)F]FLT, K ( i ), determined by non-linear
      regression (NLR) of an irreversible two-tissue compartment model was used as the
      gold standard. In addition to Patlak graphical analysis, standardised uptake
      values (SUV) and tumour-to-whole blood ratio (TBR) were used for analysing
      [(18)F]FLT data. Correlations and relationships between simplified uptake
      measures and NLR before and after chemotherapy were assessed using regression
      analysis. RESULTS: No significant differences in both pre- and post-chemotherapy
      relationships between any of the simplified uptake measures and NLR were found.
      However, changes in SUV between baseline and post-therapy scans showed a
      significant negative bias and slope less than one, while TBR did not.
      CONCLUSIONS: In LABC, TBR instead of SUV may be preferred for monitoring response
      to chemotherapy with [(18)F]FLT.

PMID- 22392643
TI  - Longitudinal PET imaging of doxorubicin-induced cell death with 18F-Annexin V.
AB  - PURPOSE: This study aims to apply longitudinal positron emission tomography (PET)
      imaging with (18)F-Annexin V to visualize and evaluate cell death induced by
      doxorubicin in a human head and neck squamous cell cancer UM-SCC-22B tumor
      xenograft model. PROCEDURES: In vitro toxicity of doxorubicin to UM-SCC-22B cells
      was determined by a colorimetric assay. Recombinant human Annexin V protein was
      expressed and purified. The protein was labeled with fluorescein isothiocyanate
      for fluorescence staining and (18)F for PET imaging. Established UM-SCC-22B
      tumors in nude mice were treated with two doses of doxorubicin (10 mg/kg each
      dose) with 1 day interval. Longitudinal (18)F-Annexin V PET was performed at 6 h,
      24 h, 3 days, and 7 days after the treatment started. Following PET imaging,
      direct tissue biodistribution study was performed to confirm the accuracy of PET
      quantification. RESULTS: Two doses of doxorubicin effectively inhibited the
      growth of UM-SCC-22B tumors by inducing cell death including apoptosis. The cell
      death was clearly visualized by (18)F-Annexin V PET. The peak tumor uptake, which
      was observed at day 3 after treatment started, was significantly higher than that
      in the untreated tumors (1.56 +/- 0.23 vs. 0.89 +/- 0.31%ID/g, p < 0.05).
      Moreover, the tumor uptake could be blocked by co-injection of excess amount of
      unlabeled Annexin V protein. At day 7 after treatment, the tumor uptake of (18)F
      Annexin had returned to baseline level. CONCLUSIONS: (18)F-Annexin V PET imaging
      is sensitive enough to allow visualization of doxorubicin-induced cell death in
      UM-SCC-22B xenograft model. The longitudinal imaging with (18)F-Annexin will be
      helpful to monitor early response to chemotherapeutic anti-cancer drugs.

PMID- 22392644
TI  - Androgen pathway stimulates microRNA-216a transcription to suppress the tumor
      suppressor in lung cancer-1 gene in early hepatocarcinogenesis.
AB  - Deregulation of microRNAs (miRNAs) is common in advanced human hepatocellular
      carcinoma (HCC); however, the ones involved in early carcinogenesis have not yet
      been investigated. By examining the expression of 22 HCC-related miRNAs between
      precancerous and cancerous liver tissues, we found miR-216a and miR-224 were
      significantly up-regulated, starting from the precancerous stage. Furthermore,
      the elevation of miR-216a was mainly identified in male patients. To study this
      gender difference, we demonstrated that pri-miR-216a is activated
      transcriptionally by the androgen pathway in a ligand-dependent manner and is
      further enhanced by the hepatitis B virus X protein. The transcription initiation
      site for pri-miR-216a was delineated, and one putative androgen-responsive
      element site was identified within its promoter region. Mutation of this site
      abolished the elevation of pri-miR-216a by the androgen pathway. One target of
      miR-216a was shown to be the tumor suppressor in lung cancer-1 gene (TSLC1)
      messenger RNA (mRNA) through the three target sites at its 3' untranslated
      region. Finally, the androgen receptor level increased in male liver tissues
      during hepatocarcinogenesis, starting from the precancerous stage, with a
      concomitant elevation of miR-216a but a decrease of TSLC1. CONCLUSION: The
      current study discovered the up-regulation of miRNA-216a by the androgen pathway
      and a subsequent suppression of TSLC1 as a new mechanism for the androgen pathway
      in early hepatocarcinogenesis.

PMID- 22392645
TI  - Prospective self-gated nonenhanced magnetic resonance angiography of the
      peripheral arteries.
AB  - Most nonenhanced MRA techniques for evaluating peripheral artery disease (PAD)
      require cardiac synchronization through physiological gating.
      Electrocardiographic gating is the most popular method for cardiac
      synchronization; however, it is subject to interference from switching magnetic
      field gradients and radiofrequency pulses. A method is described for self-gated
      nonenhanced MRA that does not require the use of electrocardiographic gating.
      Imaging was prospectively triggered by detecting the acceleration of blood flow
      during systole with a reference-less phase contrast navigator. The technique was
      implemented for nonsubtractive nonenhanced MRA using quiescent-interval single
      shot MRA. The lower extremity peripheral arteries of eight healthy subjects were
      imaged using electrocardiographic-, pulse-, and self-gated quiescent-interval
      single-shot. Self-gated quiescent-interval single-shot triggered with 99%
      accuracy. There were no significant differences in relative contrast, contrast-to
      noise ratio, or image quality between self-gated and electrocardiographic-gated
      quiescent-interval single-shot MRA (P > 0.05). Image quality with pulse gating
      was inferior.

PMID- 22392646
TI  - Endonasal repair of septal perforations using a rotational mucosal flap and
      acellular dermal interposition graft.
AB  - BACKGROUND: The closure of nasal septal perforations can be challenging based on
      the etiology, location, and method of closure. We report on a novel method of
      closure for nasal septal perforations using a unilateral mucosal rotational flap
      and acellular dermal interposition graft. METHODS: Twenty patients with nasal
      septal perforations of various etiologies underwent our method of repair through
      a closed, endonasal approach. RESULTS: Out of 20 patients, 17 demonstrated
      successful closure of their septal perforations, consistent with an 85% success
      rate. Based upon size, closure rates were 89% for small perforations (<1 cm), 80%
      for medium perforations (1-2 cm), and complete closure for a single large
      perforation (>2 cm). Of 20 patients, 19 were completely asymptomatic following
      surgical intervention, and of the 3 with failed repairs, only 1 patient required
      revision surgery for persistent symptoms. CONCLUSION: Nasal septal perforations
      may cause bothersome symptoms and present a significant reconstructive challenge.
      Native septal tissue is advantageous due to a rich vascular supply and proximity
      to the defect, while interposition grafts act as a scaffold for the migration of
      respiratory mucosa. The method described herein combines these principles to
      provide a suitable technique for the closure of nasal septal perforations.

PMID- 22392647
TI  - Effect of core epitope modification on the antibody recognition of a MUC2 mucin
      peptide.
AB  - Identification of protein epitopes via combinatorial chemistry was one of the
      most important discoveries of the past three decades. Mapping of linear antibody
      epitopes can be achieved rapidly and cost-effectively by the polymer pin-bound
      peptide approach. In this article, the determination of the fine epitope
      structure of MUC2 mucin glycoprotein is described by using specific monoclonal
      antibody. We have used positional scanning combinatorial approach, and also
      parallel synthesis. The residues within the MUC2 epitope (18)PTGTQ(22) of MAb 996
      were replaced by all other proteinogenic amino acids on pin-bound peptide
      libraries, and their antibody binding was studied in modified ELISA. Thr(19) was
      the least important of the residues in antibody recognition; most of the other
      amino acids could be replaced, except Pro. The other residues cannot be replaced
      without loss of antibody binding, where both the size and character of the amino
      acids were important. The significance of the non-chiral Gly(20) residue was
      further studied by competitive ELISA of parallelly synthesized soluble peptides
      containing L - or D-Ala instead of Gly residue. However, the D-Ala-containing
      oligopeptides showed no antibody binding; therefore, the backbone conformation is
      characteristic of that of L-amino acid containing peptides in this position as
      well. With the combinatorial approach we obtained relevant information about the
      contribution of individual amino acid side chains to the MAb 996 antibody binding
      within the PTGTQ predominant MUC2 mucin epitope. These results could be utilized
      for the design of synthetic antigens for detection of MUC2 protein core-specific
      antibodies related to carcinoma(s).

PMID- 22392648
TI  - Synthesis and in vitro inhibition properties of oligonucleotide conjugates
      carrying amphipathic proline-rich peptide derivatives of the sweet arrow peptide
      (SAP).
AB  - In this study, a series of derivatives of the amphipathic proline-rich sweet
      arrow peptide (SAP) were covalently linked to antisense oligonucleotides designed
      to inhibit Renilla luciferase gene. Oligonucleotide-peptide conjugates carrying
      lysine (Lys) and ornithine (Orn) residues were prepared using the stepwise
      approach by assembling first the peptide sequence followed by the assembly of the
      DNA molecule. The resulting Lys, Orn-conjugates were transformed to the
      corresponding arginine and homoarginine oligonucleotide-peptide conjugates by
      reaction with O-methylisourea. The introduction of the SAP at 3'-termini of a
      phosphorothioate oligonucleotide did not affect the ability to inhibit gene
      expression when transfected with lipofectamine. However, these conjugates were
      not able to enter cells without transfecting agent. Further studies using SAP as
      a transfection agent showed promising results for the conjugates carrying the Orn
      SAP. All conjugates showed high duplex stabilities.

PMID- 22392649
TI  - In vitro evidence for the brain glutamate efflux hypothesis: brain endothelial
      cells cocultured with astrocytes display a polarized brain-to-blood transport of
      glutamate.
AB  - The concentration of the excitotoxic amino acid, L-glutamate, in brain
      interstitial fluid is tightly regulated by uptake transporters and metabolism in
      astrocytes and neurons. The aim of this study was to investigate the possible
      role of the blood-brain barrier endothelium in brain L-glutamate homeostasis.
      Transendothelial transport- and accumulation studies of (3) H-L-glutamate, (3) H
      L-aspartate, and (3) H-D-aspartate in an electrically tight bovine
      endothelial/rat astrocyte blood-brain barrier coculture model were performed.
      After 6 days in culture, the endothelium displayed transendothelial resistance
      values of 1014 +/- 70 Omega cm(2) , and (14) C-D-mannitol permeability values of
      0.88 +/- 0.13 * 10(-6) cm s(-1) . Unidirectional flux studies showed that L
      aspartate and L-glutamate, but not D-aspartate, displayed polarized transport in
      the brain-to-blood direction, however, all three amino acids accumulated in the
      cocultures when applied from the abluminal side. The transcellular transport
      kinetics were characterized with a K(m) of 69 +/- 15 MUM and a J(max) of 44 +/-
      3.1 pmol min(-1) cm(-2) for L-aspartate and a K(m) of 138 +/- 49 MUM and J(max)
      of 28 +/- 3.1 pmol min(-1) cm(-2) for L-glutamate. The EAAT inhibitor, DL-threo
      beta-Benzyloxyaspartate, inhibited transendothelial brain-to-blood fluxes of L
      glutamate and L-aspartate. Expression of EAAT-1 (Slc1a3), -2 (Slc1a2), and -3
      (Slc1a1) mRNA in the endothelial cells was confirmed by conventional PCR and
      localization of EAAT-1 and -3 in endothelial cells was shown with
      immunofluorescence. Overall, the findings suggest that the blood-brain barrier
      itself may participate in regulating brain L-glutamate concentrations.

PMID- 22392650
TI  - Synthesis of uranium materials under extreme conditions: UO2[B3Al4O11(OH)], a
      complex 3D aluminoborate.

PMID- 22392652
TI  - Is the CPAP estimate of the apnea-hypopnea index on therapy clinically useful?

PMID- 22392651
TI  - Polysomnographic findings in Rett syndrome: a case-control study.
AB  - PURPOSE: Rett syndrome is a severe neurodevelopmental disorder mainly affecting
      females and usually linked to mutations in the methyl-CpG-binding protein 2 gene,
      with an estimated prevalence of 1 in 10,000 live female births. Clinical features
      which usually become more apparent over time include breathing dysfunction,
      seizures, spasticity, peripheral vasomotor disturbance, scoliosis, growth
      retardation, and hypotrophic feet, with a great variety of presentations. The
      clear immaturity in brainstem mechanisms is expressed by the presence of early
      sleep disorders such as nocturnal awakenings, bruxism, and difficulty falling
      asleep, and no conclusive findings were derived from the few polysomnographic
      studies about the sleep macrostructural aspects. The aim of this study is to
      analyze the sleep macrostructural parameters, the nocturnal respiratory
      characteristic, and the presence of periodic limb movements in a sample of
      children affected by Rett syndrome. MATERIALS: Thirteen Rett subjects underwent a
      polysomnographic study, and the findings were compared with those obtained by a
      group of 40 healthy children. RESULTS: The Rett group shows a great impairment in
      sleep macrostructural and respiratory parameters, with a higher percentage of
      pathological periodic limb movements than the controls. CONCLUSIONS: This study
      may be considered a report about the ventilatory impairment during sleep in Rett
      syndrome and the first approach to the macrostructural aspects of sleep supported
      by the PSG data that could be considered mandatory for a better comprehension of
      this very complex syndrome.

PMID- 22392653
TI  - NS5A: a new target for antiviral drugs in the treatment of hepatitis C virus
      infection.

PMID- 22392655
TI  - 'Shoo-in' strategies bump up against reality.

PMID- 22392654
TI  - Accelerated contrast-enhanced whole-heart coronary MRI using low-dimensional
      structure self-learning and thresholding.
AB  - We sought to evaluate the efficacy of prospective random undersampling and low
      dimensional-structure self-learning and thresholding reconstruction for highly
      accelerated contrast-enhanced whole-heart coronary MRI. A prospective random
      undersampling scheme was implemented using phase ordering to minimize artifacts
      due to gradient switching and was compared to a randomly undersampled acquisition
      with no profile ordering. This profile-ordering technique was then used to
      acquire contrast-enhanced whole-heart coronary MRI in 10 healthy subjects with 4
      fold acceleration. Reconstructed images and the acquired zero-filled images were
      compared for depicted vessel length, vessel sharpness, and subjective image
      quality on a scale of 1 (poor) to 4 (excellent). In a pilot study, contrast
      enhanced whole-heart coronary MRI was also acquired in four patients with
      suspected coronary artery disease with 3-fold acceleration. The undersampled
      images were reconstructed using low-dimensional-structure self-learning and
      thresholding, which showed significant improvement over the zero-filled images in
      both objective and subjective measures, with an overall score of 3.6 +/- 0.5.
      Reconstructed images in patients were all diagnostic. Low-dimensional-structure
      self-learning and thresholding reconstruction allows contrast-enhanced whole
      heart coronary MRI with acceleration as high as 4-fold using clinically available
      five-channel phased-array coil.

PMID- 22392656
TI  - The 'sleeper' issues before the Supreme Court as it reviews the Affordable Care
      Act.

PMID- 22392657
TI  - David Brailer and Farzad Mostashari: two national health IT czars compare notes.
      Interview by David J Brailer.

PMID- 22392658
TI  - The need to incorporate health information technology into physicians' education
      and professional development.
AB  - Nationwide, as physicians and health care systems adopt electronic health
      records, health information technology is becoming integral to the practice of
      medicine. But current medical education and professional development curricula do
      not systematically prepare physicians to use electronic health records and the
      data these systems collect. We detail how training in meaningful use of
      electronic health records could be incorporated into physician training, from
      medical school, through licensure and board certification, to continuing medical
      education and the maintenance of licensure and board certification. We identify
      six near-term opportunities for professional organizations to accelerate the
      integration of health information technology into their requirements.

PMID- 22392659
TI  - Giving office-based physicians electronic access to patients' prior imaging and
      lab results did not deter ordering of tests.
AB  - Policy-based incentives for health care providers to adopt health information
      technology are predicated on the assumption that, among other things, electronic
      access to patient test results and medical records will reduce diagnostic testing
      and save money. To test the generalizability of findings that support this
      assumption, we analyzed the records of 28,741 patient visits to a nationally
      representative sample of 1,187 office-based physicians in 2008. Physicians'
      access to computerized imaging results (sometimes, but not necessarily, through
      an electronic health record) was associated with a 40-70 percent greater
      likelihood of an imaging test being ordered. The electronic availability of lab
      test results was also associated with ordering of additional blood tests. The
      availability of an electronic health record in itself had no apparent impact on
      ordering; the electronic access to test results appears to have been the key.
      These findings raise the possibility that, as currently implemented, electronic
      access does not decrease test ordering in the office setting and may even
      increase it, possibly because of system features that are enticements to
      ordering. We conclude that use of these health information technologies, whatever
      their other benefits, remains unproven as an effective cost-control strategy with
      respect to reducing the ordering of unnecessary tests.

PMID- 22392660
TI  - Patient-reported measures of psychosocial issues and health behavior should be
      added to electronic health records.
AB  - Recent legislation and delivery system reform efforts are greatly expanding the
      use of electronic health records. For these efforts to reach their full
      potential, they must actively involve patients and include patient-reported
      information about such topics as health behavior, preferences, and psychosocial
      functioning. We offer a plan for including standardized, practical patient
      reported measures as part of electronic health records, quality and performance
      indexes, the primary care medical home, and research collaborations. These
      measures must meet certain criteria, including being valid, reliable, sensitive
      to change, and available in multiple languages. Clinicians, patients, and policy
      makers also must be able to understand the measures and take action based on
      them. Including more patient-reported items in electronic health records would
      enhance health, patient-centered care, and the capacity to undertake population
      based research.

PMID- 22392661
TI  - Hospitals ineligible for federal meaningful-use incentives have dismally low
      rates of adoption of electronic health records.
AB  - The US government has dedicated substantial resources to help certain providers,
      such as short-term acute care hospitals and physicians, adopt and meaningfully
      use electronic health record (EHR) systems. We used national data to determine
      adoption rates of EHR systems among all types of inpatient providers that were
      ineligible for these same federal meaningful-use incentives: long-term acute care
      hospitals, rehabilitation hospitals, and psychiatric hospitals. Adoption rates
      for these institutions were dismally low: less than half of the rate among short
      term acute care hospitals. Specifically, 12 percent of short-term acute care
      hospitals have at least a basic EHR system, compared with 6 percent of long-term
      acute care hospitals, 4 percent of rehabilitation hospitals, and 2 percent of
      psychiatric hospitals. To advance the creation of a nationwide health information
      technology infrastructure, federal and state policy makers should consider
      additional measures, such as adopting health information technology standards and
      EHR system certification criteria appropriate for these ineligible hospitals;
      including such hospitals in state health information exchange programs; and
      establishing low-interest loan programs for the acquisition and use of certified
      EHR systems by ineligible providers.

PMID- 22392662
TI  - Obtaining providers' 'buy-in' and establishing effective means of information
      exchange will be critical to HITECH's success.
AB  - In enacting the Health Information Technology for Economic and Clinical Health
      (HITECH) provisions of the American Recovery and Reinvestment Act, Congress set
      ambitious goals for the nation to integrate information technology into health
      care delivery. The provisions called for the electronic exchange of health
      information and the adoption and meaningful use of health information technology
      in health care practices and hospitals. We examined the marketplace and
      regulatory forces that influence HITECH's success and identify outstanding
      challenges, some beyond the provisions' control. To reach HITECH's goals,
      providers and patients must be persuaded of the value of health information
      exchange and support its implementation. Privacy concerns and remaining technical
      challenges must also be overcome. Achieving HITECH's goals will require well
      aligned incentives, both visionary and practical pursuit of exchange
      infrastructure, and realistic assumptions about how quickly such wholesale change
      can be accomplished. The use of metrics to show adoption proceeding at a
      reasonable pace, increased flow of data across parties, and evidence that care is
      improving, at least in areas with robust systems, will be essential to persuade
      stakeholders that the initiative is progressing well and warrants continued
      investment.

PMID- 22392663
TI  - From the Office of the National Coordinator: the strategy for advancing the
      exchange of health information.
AB  - Electronic health information exchange addresses a critical need in the US health
      care system to have information follow patients to support patient care. Today
      little information is shared electronically, leaving doctors without the
      information they need to provide the best care. With payment reforms providing a
      strong business driver, the demand for health information exchange is poised to
      grow. The Office of the National Coordinator for Health Information Technology,
      Department of Health and Human Services, has led the process of establishing the
      essential building blocks that will support health information exchange. Over the
      coming year, this office will develop additional policies and standards that will
      make information exchange easier and cheaper and facilitate its use on a broader
      scale.

PMID- 22392664
TI  - Satisfying patient-consumer principles for health information exchange: evidence
      from California case studies.
AB  - In June 2010 sixteen organizations representing California patients and consumers
      adopted nine principles for electronically exchanging health information among
      and within provider organizations. The principles were formulated with the goal
      of improving patient and population health care by increasing the availability
      and use of patient data while protecting patients' privacy. This study assesses
      to what extent five health care organizations-all in different stages of
      increasing their capacity for health information exchange-conformed to the
      principles in early 2011. Although an increasing amount of electronic data has
      been exchanged among organizations and with patients, progress has been modest,
      and patients still have little control over their data. For organizations to
      comply with all nine patient and consumer principles, clear "rules of the road"
      for information sharing must be defined, and patient education in health
      information exchange and control over personal data must be increased.

PMID- 22392666
TI  - An experiment shows that a well-designed report on costs and quality can help
      consumers choose high-value health care.
AB  - Advocates of health reform continue to pursue policies and tools that will make
      information about comparative costs and resource use available to consumers.
      Reformers expect that consumers will use the data to choose high-value providers
      those who offer higher quality and lower prices-and thus contribute to the
      broader goal of controlling national health care spending. However, communicating
      this information effectively is more challenging than it might first appear. For
      example, consumers are more interested in the quality of health care than in its
      cost, and many perceive a low-cost provider to be substandard. In this study of
      1,421 employees, we examined how different presentations of information affect
      the likelihood that consumers will make high-value choices. We found that a
      substantial minority of the respondents shied away from low-cost providers, and
      even consumers who pay a larger share of their health care costs themselves were
      likely to equate high cost with high quality. At the same time, we found that
      presenting cost data alongside easy-to-interpret quality information and
      highlighting high-value options improved the likelihood that consumers would
      choose those options. Reporting strategies that follow such a format will help
      consumers understand that a doctor who provides higher-quality care than other
      doctors does not necessarily cost more.

PMID- 22392665
TI  - Simulation Suggests that medical group mergers won't undermine the potential
      utility of health information exchanges.
AB  - Federal and state agencies are investing substantial resources in the creation of
      community health information exchanges, which are consortia that enable
      independent health care organizations to exchange clinical data. However, under
      pressure to form accountable care organizations, medical groups may merge and
      support private health information exchanges. Such activity could reduce the
      potential utility of community exchanges-that is, the exchanges' capacity to
      share patient data across hospitals and physician practices that are independent.
      Simulations of care transitions based on data from ten Massachusetts communities
      suggest that there would have to be many such mergers to undermine the potential
      utility of health information exchanges. At the same time, because hospitals and
      the largest medical groups account for only 10-20 percent of care transitions in
      a community, information exchanges will still need to recruit a large proportion
      of the medical groups in a given community for the exchanges to maintain their
      usefulness in fostering information exchange across independent providers.

PMID- 22392667
TI  - Forging a tool to guide patients in self-care management.

PMID- 22392668
TI  - Public reporting helped drive quality improvement in outpatient diabetes care
      among Wisconsin physician groups.
AB  - Public reporting on the quality of ambulatory health care is growing, but
      knowledge of how physician groups respond to such reporting has not kept pace. We
      examined responses to public reporting on the quality of diabetes care in 409
      primary care clinics within seventeen large, multispecialty physician groups. We
      determined that a focus on publicly reported metrics, along with participation in
      large or externally sponsored projects, increased a clinic's implementation of
      diabetes improvement interventions. Clinics were also more likely to implement
      interventions in more recent years. Public reporting helped drive both early
      implementation of a single intervention and ongoing implementation of multiple
      simultaneous interventions. To fully engage physician groups, accountability
      metrics should be structured to capture incremental improvements in quality,
      thereby rewarding both early and ongoing improvement activities.

PMID- 22392669
TI  - Multistakeholder regional collaboratives have been key drivers of public
      reporting, but now face challenges.
AB  - Multistakeholder regional collaboratives have assumed a prominent role in
      producing public reports about health care providers' performance. I conducted an
      in-depth study of eight such US collaboratives, examining their accomplishments,
      management practices, and future challenges. I found that these collaboratives
      have made key contributions to public reporting and have built trust and
      cooperation among stakeholders who, in other settings, are competitive or even
      adversarial. Challenges for collaboratives include securing ongoing funding;
      negotiating complex and contentious issues around expanded reporting activities,
      such as publishing measures of providers' efficiency; and establishing more
      flexible and efficient decision-making processes.

PMID- 22392670
TI  - Medicare's public reporting initiative on hospital quality had modest or no
      impact on mortality from three key conditions.
AB  - Hospital Compare, Medicare's public reporting initiative, began reporting
      measures of hospital quality for almost all US acute care hospitals in 2005. The
      impact of this public reporting initiative on patient mortality is unknown. We
      used Medicare claims data from the period 2000-08 to estimate the effect of
      Hospital Compare on thirty-day mortality for heart attack, heart failure, and
      pneumonia. Our analysis indicates that the fact that hospitals had to report
      quality data under Hospital Compare led to no reductions in mortality beyond
      existing trends for heart attack and pneumonia and led to a modest reduction in
      mortality for heart failure. We conclude that Medicare's public reporting
      initiative for hospitals has had a minimal impact on patient mortality.

PMID- 22392671
TI  - High-profile investigations into hospital safety problems in England did not
      prompt patients to switch providers.
AB  - Amid international concerns about health care safety and quality, there has been
      an escalation of investigations by health care regulators into adverse events.
      England has a powerful central health care regulator, the Care Quality
      Commission, which conducts occasional high-profile investigations into major
      lapses in quality at individual hospitals. The results have sometimes garnered
      considerable attention from the news media, but it is not known what effect the
      investigations have had on patients' behavior. We analyzed trends in admission
      for discretionary (nonemergency) care at three hospitals that were subject to
      high-profile investigations by the Healthcare Commission (the predecessor to the
      Care Quality Commission) between 2006 and 2009. We found that investigations had
      no impact on utilization for two of the hospitals; in the third hospital, there
      were significant declines in inpatient admissions, outpatient surgeries, and in
      numbers of patients coming for their first appointment, but the effects
      disappeared six months after publication of the investigation report. Thus, the
      publication and dissemination of highly critical reports by a health care
      regulator does not appear to have resulted in patients' sustained avoidance of
      the hospitals that were investigated. Our findings reinforce other evaluations:
      Reporting designed to affect providers' reputations is likely to spur more
      improvement in quality and safety than relying on patients to choose their
      providers based on quality and safety reports, and simplistic assumptions
      regarding the power of information to drive patient choices are unrealistic.

PMID- 22392672
TI  - How report cards on physicians, physician groups, and hospitals can have greater
      impact on consumer choices.
AB  - Public report cards with quality and cost information on physicians, physician
      groups, and hospital providers have proliferated in recent years. However, many
      of these report cards are difficult for consumers to interpret and have had
      little impact on the provider choices consumers are making. To gain a more
      focused understanding of why these reports cards have not been more successful
      and what improvements could be made, we interviewed experts and surveyed
      registrants at the March 2011 AHRQ National Summit on Public Reporting for
      Consumers in Health Care. We found broad agreement that public reporting has been
      disconnected from consumer decisions about providers because of weaknesses in
      report card content, design, and accessibility. Policy makers have an opportunity
      to change the landscape of public reporting by taking advantage of advances in
      measurement, data collection, and information technology to deliver a more
      consumer-centered report card. Overcoming the constraint of limited public
      funding, and achieving the acceptance of providers, is critical to realizing
      future success.

PMID- 22392673
TI  - A five-point checklist to help performance reports incentivize improvement and
      effectively guide patients.
AB  - Public reports of provider performance on measures of the quality, costs, and
      outcomes of health care can spur improvement and help patients find the best
      providers. However, the likelihood that these benefits will materialize depends
      on the methods underlying each performance report. This paper presents a five
      point methodological checklist to guide those who want to improve their
      performance reporting methods. The central goal is to help report makers minimize
      the frequency and severity of provider performance misclassification and avoid
      adverse unintended consequences of reporting. We believe that if those who
      produce the reports publicly explain how they address each checklist item, this
      increased transparency will encourage more rigorous methods and improve the
      chances that reports will lead to better, more efficient care.

PMID- 22392674
TI  - Advancing public reporting through a new 'aggregator' to standardize data
      collection on providers' cost and quality.
AB  - Advocates for consumer-friendly public reporting on the performance of health
      care providers anticipate that, at some point, well-vetted and standardized
      measures will be widely available to help patients choose clinicians who provide
      the best care. However, achieving that goal would require assembling standardized
      data from many sources. Such an effort would raise concerns, including privacy
      considerations about having a single massive data repository; questions of how
      such an effort would be funded; and potential misuse of the data. This paper
      proposes creating a public-private data aggregator that would receive patient and
      provider data from payers that are deidentified in such a way as to remain useful
      for consumer-reporting and research purposes. The aggregator could be funded
      through fees charged to commercial users. Meanwhile, registered researchers
      putting their methods and findings in the public domain could access the data
      aggregator for free.

PMID- 22392675
TI  - Building the scaffold to improve health care quality in Western New York.
AB  - Many health policy leaders are promoting the community as a place to try out new
      ideas for improving the quality of health care. Alliances with multiple
      stakeholders are moving forward with communitywide efforts to improve the quality
      of care without the benefit of an established evidence base or guiding framework.
      This article presents a profile of one community's attempt to facilitate and
      coordinate quality improvement in its geographic area. The P(2) Collaborative of
      Western New York is one of sixteen sites supported by the Robert Wood Johnson
      Foundation's national Aligning Forces for Quality initiative. The strategy and
      vision of the collaborative has evolved as it has tried to capitalize on
      opportunities and overcome barriers in its work. The article concludes with a
      discussion of eight tasks that community alliances may consider undertaking when
      establishing an infrastructure for improving the quality of health care, such as
      convening area stakeholders to develop a strategy and finding ways to monitor
      health outcomes at the local level on an ongoing basis.

PMID- 22392676
TI  - In California, quality reporting at the state level is at a crossroads after
      hospital group pulls out.

PMID- 22392677
TI  - Chronic Lyme disease: it's time to solve the medical mystery inside an enigma.

PMID- 22392678
TI  - A future nursing shortage?

PMID- 22392681
TI  - Metallic nanobowls by galvanic replacement reaction on heterodimeric
      nanoparticles.
AB  - Well-defined metallic nanobowls can be prepared by extending the concept of a
      protecting group to colloidal synthesis. Magnetic nanoparticles are employed as
      "protecting groups" during the galvanic replacement of silver with gold. The
      replacement reaction is accompanied by spontantous dissociation of the protecting
      groups, leaving behind metallic nanobowls.

PMID- 22392683
TI  - Rheumatologists' quality of care for lupus: comparison study between a university
      and county hospital.
AB  - OBJECTIVE: Quality of care received from physicians may impact health outcomes in
      systemic lupus erythematosus (SLE). We compared physician quality of care (P
      QOC), health-related quality of life (HRQOL), and disease activity and damage
      between SLE patients receiving outpatient care at a university and a county
      rheumatology clinic. METHODS: Forty-two university and 41 county clinic SLE
      patients provided data on 5 P-QOC parameters and HRQOL health outcomes (Short
      Form 36 [SF-36] health survey and EuroQol 5-domain instrument [EQ-5D]). Disease
      activity and damage were measured. Chi-square analysis and Student's t-tests were
      used for comparisons. RESULTS: Overall satisfaction with medical care was
      similar; however, university patients had higher P-QOC scores than county
      patients in "perception of doctor's understanding of impact of SLE on patient's
      life" (P = 0.02) and "providing education/educational information to understand
      their disease" (P = 0.05). HRQOL, disease activity, and damage were similar in
      the 2 groups. Overall satisfaction with medical care was directly related SF-36
      general health (r = 0.34, P = 0.03) and EQ-5D visual analog scale on state of
      health (r = 0.39, P = 0.01), and inversely related EQ-5D pain (r = -0.37, P =
      0.02). CONCLUSION: Patient perceptions of P-QOC differed across the 2 centers
      despite similar demographics, clinical and HRQOL outcomes, and significant
      overlap in the physicians serving each clinic. Patients' overall satisfaction
      with medical care is associated with better HRQOL.

PMID- 22392684
TI  - Sensitivity analysis on parameters and processes affecting vapor intrusion risk.
AB  - A one-dimensional numerical model was developed and used to identify the key
      processes controlling vapor intrusion risks by means of a sensitivity analysis.
      The model simulates the fate of a dissolved volatile organic compound present
      below the ventilated crawl space of a house. In contrast to the vast majority of
      previous studies, this model accounts for vertical variation of soil water
      saturation and includes aerobic biodegradation. The attenuation factor (ratio
      between concentration in the crawl space and source concentration) and the
      characteristic time to approach maximum concentrations were calculated and
      compared for a variety of scenarios. These concepts allow an understanding of
      controlling mechanisms and aid in the identification of critical parameters to be
      collected for field situations. The relative distance of the source to the
      nearest gas-filled pores of the unsaturated zone is the most critical parameter
      because diffusive contaminant transport is significantly slower in water-filled
      pores than in gas-filled pores. Therefore, attenuation factors decrease and
      characteristic times increase with increasing relative distance of the
      contaminant dissolved source to the nearest gas diffusion front. Aerobic
      biodegradation may decrease the attenuation factor by up to three orders of
      magnitude. Moreover, the occurrence of water table oscillations is of importance.
      Dynamic processes leading to a retreating water table increase the attenuation
      factor by two orders of magnitude because of the enhanced gas phase diffusion.

PMID- 22392685
TI  - Carbon-silicon Schottky barrier diodes.
AB  - The simple fabrication of high-performance Schottky barrier diodes between
      silicon and conductive carbon films (C-Films) is reported. By optimizing the
      interface, ideality factors as low as n = 1.22 for pyrolytic photoresist films
      (PPF) have been obtained. These remarkable values, which are not far away from
      those of commercial products are obtained repeatedly on non-optimized substrates
      with fully scalable processes.

PMID- 22392686
TI  - GSTM1 and GSTT1 copy numbers and mRNA expression in lung cancer.
AB  - Large fractions of the human population do not express GSTM1 and GSTT1 (GSTM1/T1)
      enzymes because of deletions in these genes. These variations affect xenobiotic
      metabolism and have been evaluated in relation to lung cancer risk, mostly based
      on null/present gene models. We measured GSTM1/T1 heterozygous deletions, not
      tested in genome-wide association studies, in 2,120 controls and 2,100 cases from
      the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We evaluated
      their effect on mRNA expression on lung tissue and peripheral blood samples and
      their association with lung cancer risk overall and by histology types. We tested
      the null/present, dominant, and additive models using logistic regression.
      Cigarette smoking and gender were studied as possible modifiers. Gene expression
      from blood and lung tissue cells was strongly down regulated in subjects carrying
      GSTM1/T1 deletions by both trend and dominant models (P < 0.001). In contrast to
      the null/present model, analyses distinguishing subjects with 0, 1, or 2 GSTM1/T1
      deletions revealed several associations. There was a decreased lung cancer risk
      in never-smokers (OR = 0.44; 95%CI = 0.23-0.82; P = 0.01) and women (OR = 0.50;
      95%CI = 0.28-0.90; P = 0.02) carrying 1 or 2 GSTM1 deletions. Analogously, male
      smokers had an increased risk (OR = 1.13; 95%CI = 1.0-1.28; P = 0.05) and women a
      decreased risk (OR = 0.78; 95%CI = 0.63-0.97; P = 0.02) for increasing GSTT1
      deletions. The corresponding gene smoking and gene-gender interactions were
      significant (P < 0.05). Our results suggest that decreased activity of GSTM1/T1
      enzymes elevates lung cancer risk in male smokers, likely due to impaired
      carcinogens' detoxification. A protective effect of the same mutations may be
      operative in never-smokers and women, possibly because of reduced activity of
      other genotoxic chemicals.

PMID- 22392687
TI  - Characteristics of an aerobic denitrifier that utilizes ammonium and nitrate
      simultaneously under the oligotrophic niche.
AB  - INTRODUCTION: An aerobic denitrifier was isolated from the Hua-Jia-Chi pond in
      China and identified as Pseudomonas mendocina 3-7 (Genbank No. HQ285879). This
      isolated strain could express periplasmic nitrate reductase which is essential
      for aerobic denitrification occurred when the dissolved oxygen (DO) level
      maintains at 3-10 mg L(-1). METHODS: To determine whether the ability of isolated
      strain is exhibited in the bioremediation of polluted drinking source water, the
      heterotrophic nitrification and aerobic denitrification characteristics of P.
      mendocina 3-7 under different cultural conditions such as oxygen level, nitrate
      and organic concentrations were studied from the nitrogenous balance in the
      paper. RESULTS AND CONCLUSIONS: By measuring the nitrogen balance in all
      experiments under different culture conditions, the removal of total organic
      carbon and ammonium was positively correlated with total nitrogen removal,
      especially under high substrate level. With substrate concentration decreasing,
      ammonium and nitrate removal occurred separately, and ammonium was completely
      utilized first under low substrate concentration. Compared to that under high
      substrate level, the specific growth rate of P. mendocina 3-7 was not low under
      the low substrate level and the pollutant removal efficiencies remained high,
      which implies the stronger nitrogen removal and acclimatization capacities of the
      strain in oligotrophic niches.

PMID- 22392688
TI  - Exposure to toxic waste containing high concentrations of hydrogen sulphide
      illegally dumped in Abidjan, Cote d'Ivoire.
AB  - INTRODUCTION: On August 2006, a cargo ship illegally dumped 500 t of toxic waste
      containing high concentrations of hydrogen sulphide in numerous sites across
      Abidjan. Thousands of people became ill. Seventeen deaths were associated with
      toxic waste exposure. MATERIALS AND METHODS: This study reports on environmental
      and health problems associated with the incident. A cross-sectional transect
      study was conducted in five waste dumping site areas. RESULTS: Of the households,
      62.1% (n = 502) were exposed to the effects of the pollutants and 51.1% of the
      interviewed people (n = 2,368) in these households showed signs of poisoning.
      Most important symptoms were cough (37.1%), asthenia (33.1%), pruritus (29.9%)
      and nausea (29.1%). DISCUSSION: The health effects showed different frequencies
      in the five waste impact sites. Among the poisoned persons, 21.1% (n = 532)
      presented symptoms on the survey day (i.e., 4 months after incident). Transect
      sampling allowed to determine a radius of vulnerability to exposure of up to 3 km
      from the point of toxic waste disposal. CONCLUSION: The area of higher
      vulnerability is influenced by various environmental factors, such as size and
      severity of pollution site, duration of toxic waste pollution on the impact site
      and locally climatic conditions. The surveillance of effects on environment and
      human health is warranted to monitor the development.

PMID- 22392689
TI  - Performance evaluation of a tailor-made passive sampler for monitoring of
      tropospheric ozone.
AB  - INTRODUCTION: This study presents the performance evaluation of a tailor-made
      passive sampler developed for the monitoring of tropospheric ozone. METHODS: The
      performance of the passive sampler was tested in the field conditions in terms of
      accuracy, precision, blank values, detection limit, effects of some parameters
      such as sampling site characteristics and sampling period on the field blanks,
      self-consistency, experimental and theoretical uptake rates, shelf life and
      comparison with commercial passive samplers. RESULTS: There was an agreement (R
      (2) = 0.84) between the responses of passive sampler and the continuous automatic
      analyser. The accuracy of the sampler, expressed as percent relative error, was
      obtained lower than 15%. Method precision in terms of coefficient of variance for
      three simultaneously applied passive samplers was 12%. Sampler detection limit
      was 2.42 MUg m(-3) for an exposure period of 1 week, and the sampler can be
      stored safely for a period of up to 8 weeks before exposure. Satisfactory self
      consistency results showed that extended periods gave the same integrated
      response as a series of short-term samplers run side by side. The uptake rate of
      ozone was found to be 10.21 mL min(-1) in a very good agreement with the
      theoretical uptake rate (10.32 mL min(-1)). The results of the comparison study
      conducted against a commercially available diffusion tube (Gradko diffusion tube)
      showed a good linear relationship (R (2) = 0.93) between two passive samplers.
      CONCLUSIONS: The sampler seems suitable to be used in large-scale measurements of
      ozone where no data are available or the number of existing automated monitors is
      not sufficient.

PMID- 22392690
TI  - In vitro metabolism of hydroxylated polybrominated diphenyl ethers and their
      inhibitory effects on 17beta-estradiol metabolism in rat liver microsomes.
AB  - PURPOSE: Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have emerged as
      contaminants of environmental concerns because they pose potential risks to human
      and animal health. The purpose of this study was to investigate the in vitro
      metabolism of OH-PBDEs and their potential inhibition against 17beta-estradiol
      (E2) metabolism. METHODS: Rat liver microsomes were used as a source of P450
      enzymes in an in vitro metabolism study of OH-PBDEs. Inhibition of E2 metabolism
      and kinetic study were performed by incubating with rat liver microsomes in the
      presence of OH-PBDEs. RESULTS: The obtained data clearly demonstrated that OH
      PBDEs, especially those congeners with lower bromination, could be metabolized to
      bromophenol and diOH-PBDEs. The less metabolic rate of OH-PBDEs was observed with
      the increasing number of bromine substituents. OH-PBDEs with hydroxyl group and
      bromine adjacent to the ether bridge showed faster metabolic rates. In addition,
      the results showed non-competitive inhibition of E2 metabolism by OH-PBDEs with
      IC(50) values in the range from 13.7 to 55.2 MUM. The most potent OH-PBDE
      inhibitor was found to be 3'-OH-BDE-100. The inhibitory potencies for OH-PBDEs
      were significantly higher than those of parent PBDE and methoxylated metabolites,
      providing the evidence that PBDEs exerted estrogenic activity in part by their
      hydroxylated metabolites. CONCLUSIONS: OH-PBDEs exhibited large differences in
      their capacity to be metabolized and to inhibit E2 metabolism in rat liver
      microsomes. The finding might increase our understanding of healthy risk
      associated with PBDEs in human and wildlife.

PMID- 22392691
TI  - Detection and quantitative analysis of 21 veterinary drugs in river water using
      high-pressure liquid chromatography coupled to tandem mass spectrometry.
AB  - INTRODUCTION: The use of veterinary drugs in food production focuses on the
      control and improvement of animal health. The disadvantage of this practice is
      that pharmaceuticals and their metabolites are released into the environment,
      finding their way to natural water systems and becoming a potential risk to non
      target organism. METHODS: This paper reports the development and validation of a
      quantitative method, based on high-performance liquid chromatography coupled to
      tandem mass spectrometry, for the simultaneous analysis of 21 veterinary drugs,
      antimicrobials, corticosteroids, coccidiostats and antifungal agents, in surface
      water. RESULTS: The precision of the method was established by calculating the
      mean recoveries, which were in the range of 94-101%. The developed method was
      employed to conduct the first monitoring study on the presence of veterinary
      drugs in the Galicia region, Northwest of Spain and was applied to 235 surface
      water samples. Eleven veterinary drugs were detected at concentrations from below
      the limit of quantification to 2,978.6 ng L(-1). Limits of detection and
      quantification were in the range of 6.2 (betamethasone, cortisone, decoquinate,
      dexamethasone, maduramycin, monensin, narasin, salinomycin,
      sulfachloropyridazine, sulfamethoxypyridazine and trimethoprim) to 12.5 ng L(-1)
      (for the rest of the selected drugs) and 12.5 (betamethasone, cortisone,
      decoquinate, dexamethasone, maduramycin, monensin, narasin, salinomycin,
      sulfachloropyridazine, sulfamethoxypyridazine and trimethoprim) to 25.0 ng L(-1)
      (for the remaining pharmaceuticals), respectively. CONCLUSION: Sulfonamides were
      the group most frequently found, which are widely used in veterinary medicine.

PMID- 22392692
TI  - Biosorption of cadmium(II) and copper(II) ions from aqueous solution by core of
      Artocarpus odoratissimus.
AB  - PURPOSE: This research is on the evaluation of biosorption capability of the core
      of Artocarpus odoratissimus (Tarap), grown in Brunei Darussalam, towards Cd(II)
      and Cu(II) ions present in synthetic solutions, and to characterize the surface
      of Tarap particles. METHODS: Thermogravimetric analysis and surface titrations
      were conducted to characterize the surface of dried Tarap core particles. Atomic
      absorption spectroscopic measurements were conducted to determine the extent of
      removal of Cd(II) and Cu(II) under different experimental conditions. RESULTS:
      Mass reductions associated with many exothermic reaction peaks were observed
      beyond 200 degrees C up to 650 degrees C indicating the combustion of organic
      matter in Tarap. Dried particles of core of Tarap bear a negative surface charge
      promoting strong interaction towards positively charged ions, such as Cu(II) and
      Cd(II). Biosorption of the two metal ions on Tarap, which is relatively high
      beyond pH = 4, occurs within a short period of exposure time. The extent of
      biosorption is enhanced by acid treatment of the biosorbent, and further it does
      not significantly depend on the presence of nonreacting ions up to an ionic
      strength of 2.0 M. CONCLUSION: Strong attraction between each metal ion and the
      biosorbent is attributed to the negative surface charge on the biosorbent within
      a broad pH range. Acid treatment of the biosorbent improves sorption
      characteristics, suggesting that ion exchange plays an important role in the
      metal ion-biosorbent interaction process.

PMID- 22392693
TI  - Synthesis of alpha-Fe2O3 nanofibers for applications in removal and recovery of
      Cr(VI) from wastewater.
AB  - PURPOSE: Nanomaterials such as iron oxides and ferrites have been intensively
      investigated for water treatment and environmental remediation applications. The
      purpose of this work is to synthesize alpha-Fe(2)O(3) nanofibers for potential
      applications in removal and recovery of noxious Cr(VI) from wastewater. METHODS:
      alpha-Fe(2)O(3) nanofibers were synthesized via a simple hydrothermal route
      followed by calcination. The crystallographic structure and the morphology of the
      as-prepared alpha-Fe(2)O(3) nanofibers were characterized by X-ray diffraction,
      scanning electron microscope, and transmission electron microscope. Batch
      adsorption experiments were conducted, and Fourier transform infrared spectra
      were recorded before and after adsorption to investigate the Cr(VI) removal
      performance and adsorption mechanism. Langmuir and Freundlich modes were employed
      to analyze the adsorption behavior of Cr(VI) on the alpha-Fe(2)O(3) nanofibers.
      RESULTS: Very thin and porous alpha-Fe(2)O(3) nanofibers have been successfully
      synthesized for investigation of Cr(VI) removal capability from synthetic
      wastewater. Batch experiments revealed that the as-prepared alpha-Fe(2)O(3)
      nanofibers exhibited excellent Cr(VI) removal performance with a maximum
      adsorption capacity of 16.17 mg g(-1). Furthermore, the adsorption capacity
      almost kept unchanged after recycling and reusing. The Cr(VI) adsorption process
      was found to follow the pseudo-second-order kinetics model, and the corresponding
      thermodynamic parameters DeltaG degrees , DeltaH degrees , and DeltaS degrees  at
      298 K were calculated to be -26.60 kJ mol(-1), -3.32 kJ mol(-1), and 78.12 J mol(
      1) K(-1), respectively. CONCLUSIONS: The as-prepared alpha-Fe(2)O(3) nanofibers
      can be utilized as efficient low-cost nano-absorbents for removal and recovery of
      Cr(VI) from wastewater.

PMID- 22392694
TI  - TAT-apoptosis repressor with caspase recruitment domain protein transduction
      rescues mice from fulminant liver failure.
AB  - Acute liver failure (ALF) is associated with massive hepatocyte cell death and
      high mortality rates. Therapeutic approaches targeting hepatocyte injury in ALF
      are hampered by the activation of distinct stimulus-dependent pathways, mechanism
      of cell death, and a limited therapeutic window. The apoptosis repressor with
      caspase recruitment domain (ARC) is a recently discovered death repressor that
      inhibits both death receptor and mitochondrial apoptotic signaling. Here, we
      investigated the in vivo effects of ARC fused with the transduction domain of
      human immunodeficiency virus 1 (HIV-1) (TAT-ARC) on Fas- and tumor necrosis
      factor (TNF)-mediated murine models of fulminant liver failure. Treatment with
      TAT-ARC protein completely abrogated otherwise lethal liver failure induced by
      Fas-agonistic antibody (Jo2), concanavalin A (ConA), or D
      galactosamine/lipopolysaccharide (GalN/LPS) administration. Importantly, survival
      of mice was even preserved when TAT-ARC therapy was initiated in a delayed manner
      after stimulation with Jo2, ConA, or GalN/LPS. ARC blocked hepatocyte apoptosis
      by directly interacting with members of the death-inducing signaling complex. TNF
      mediated liver damage was inhibited by two independent mechanisms: inhibition of
      jun kinase (JNK)-mediated TNF-alpha expression and prevention of hepatocyte
      apoptosis by inhibition of both death receptor and mitochondrial death signaling.
      We identified JNK as a novel target of ARC. ARC's caspase recruitment domain
      (CARD) directly interacts with JNK1 and JNK2, which correlates with decreased JNK
      activation and JNK-dependent TNF-alpha production. CONCLUSION: This work suggests
      that ARC confers hepatoprotection upstream and at the hepatocyte level. The
      efficacy of TAT-ARC protein transduction in multiple murine models of ALF
      demonstrates its therapeutic potential for reversing liver failure.

PMID- 22392695
TI  - Safety and efficacy of abatacept in eight rheumatoid arthritis patients with
      chronic hepatitis B.
AB  - OBJECTIVE: There are no previous studies on the use of abatacept in patients with
      chronic hepatitis B. This medical record review assessed the safety and efficacy
      of abatacept in 8 patients with rheumatoid arthritis (RA) and chronic hepatitis
      B. METHODS: A retrospective analysis of patients with RA and chronic hepatitis B
      treated with abatacept was conducted. The primary outcome was the 4-variable
      Disease Activity Score in 28 joints using the erythrocyte sedimentation rate
      (DAS28-ESR) at each followup visit along with markers of hepatitis B
      reactivation, including aspartate aminotransferase, alanine aminotransferase, and
      hepatitis B viral load. RESULTS: A total of 47 visit data points were recorded.
      The mean +/- SD duration of followup of patients receiving abatacept was 19.1 +/-
      12.7 months (range 3-33 months). Analysis was limited to 18 months of followup
      (included 77% of all visits [36 of 47]). Four patients were started on antiviral
      prophylaxis for hepatitis B with the initiation of abatacept, while 4 patients
      were not. Among the 4 patients who received antiviral prophylaxis, RA improved as
      evidenced by a statistically significant decrease in DAS28-ESR scores, and none
      had reactivation of hepatitis B. In the 4 patients without antiviral prophylaxis,
      there was no significant decrease in the DAS28-ESR scores and all 4 experienced
      reactivation of hepatitis B. There were no adverse events other than the
      hepatitis B reactivation. CONCLUSION: Use of abatacept in patients with RA and
      chronic hepatitis B appears feasible if antiviral prophylaxis for hepatitis B is
      given concurrently. In these patients there were no non-hepatitis-related adverse
      effects. These data are encouraging and should lead to initiation of controlled
      trials of abatacept in hepatitis B.

PMID- 22392696
TI  - DNA-wrapped carbon nanotubes as sensitive electrochemical labels in controlled
      assembly-mediated signal transduction for the detection of sequence-specific DNA.
AB  - A novel electrochemical strategy that uses DNA-wrapped carbon nanotubes (CNTs) as
      electrochemical labels is developed for sensitive and selective detection of
      sequence-specific DNA. The presence of target DNA mediates the formation of a
      sandwiched complex between the DNA-wrapped CNT and a hairpin DNA capture probe
      immobilized on magnetic beads. This allows target-selective collection of the CNT
      labels by magnetic separation and transfer on the electrode surface modified with
      an insulating self-assembled monolayer (SAM). After treatment with N,N
      dimethylformamide, the collected sandwiched complex releases the bare CNTs and
      facilitates the removal of magnetic beads from the electrode surface. The bare
      CNTs can then assemble on the SAM-modified electrode surface and mediate
      efficient electron transfer between the electrode and the electroactive species
      in the solution with a strong current signal generated. The results indicate that
      the developed strategy shows a sensitive response to target DNA with a desirable
      signal gain and a low detection limit of 0.9 pM. This strategy is also
      demonstrated to provide excellent differentiation of single-base mismatch in
      target DNA. It is expected that this electrochemical strategy may hold great
      potential as a novel platform for clinical diagnostics and genetic analysis.

PMID- 22392698
TI  - Complete NMR assignment of 3, 4-seco-lup-20(29)-en-3-oic acid from Decatropis
      bicolor.
AB  - Complete (1) H and (13) C NMR chemical shift assignments for 3,4-seco-lup-20(29)
      en-3-oic acid (1) have been established by means of two-dimensional COSY, HSQC,
      HMBC and NOESY spectroscopic experiments as well as by analysis of MS data.
      Compound 1 was isolated from Decatropis bicolor (Zucc.) Radlk. (Rutaceae) in
      addition to six coumarins and one alkaloid of known structure.

PMID- 22392697
TI  - Regulation of pancreatic cancer growth by superoxide.
AB  - K-ras mutations have been identified in up to 95% of pancreatic cancers, implying
      their critical role in the molecular pathogenesis. Expression of K-ras oncogene
      in an immortalized human pancreatic ductal epithelial cell line, originally
      derived from normal pancreas (H6c7), induced the formation of carcinoma in mice.
      We hypothesized that K-ras oncogene correlates with increased non-mitochondrial
      generated superoxide (O 2.-), which could be involved in regulating cell growth
      contributing to tumor progression. In the H6c7 cell line and its derivatives,
      H6c7er-Kras+ (H6c7 cells expressing K-ras oncogene), and H6c7eR-KrasT
      (tumorigenic H6c7 cells expressing K-ras oncogene), there was an increase in
      hydroethidine fluorescence in cell lines that express K-ras. Western blots and
      activity assays for the antioxidant enzymes that detoxify O 2.- were similar in
      these cell lines suggesting that the increase in hydroethidine fluorescence was
      not due to decreased antioxidant capacity. To determine a possible non
      mitochondrial source of the increased levels of O 2.-, Western analysis
      demonstrated the absence of NADPH oxidase-2 (NOX2) in H6c7 cells but present in
      the H6c7 cell lines expressing K-ras and other pancreatic cancer cell lines.
      Inhibition of NOX2 decreased hydroethidine fluorescence and clonogenic survival.
      Furthermore, in the cell lines with the K-ras oncogene, overexpression of
      superoxide dismutases that detoxify non-mitochondrial sources of O 2.-, and
      treatment with the small molecule O 2.- scavenger Tempol, also decreased
      hydroethidine fluorescence, inhibited clonogenic survival and inhibited growth of
      tumor xenografts. Thus, O 2.- produced by NOX2 in pancreatic cancer cells with K
      ras, may regulate pancreatic cancer cell growth.

PMID- 22392699
TI  - Hepatocyte senescence in vivo following preconditioning for liver repopulation.
AB  - In the retrorsine (RS)-based model of massive liver repopulation, preexposure to
      this naturally occurring alkaloid is sufficient to prime normal host parenchymal
      cells to be slowly replaced by transplanted normal hepatocytes. The basis for
      this striking effect is yet to be fully elucidated. In the present studies the
      possible involvement of cell senescence was investigated. Fischer 344 rats were
      treated according to the RS-based protocol for hepatocyte transplantation, i.e.,
      two doses of RS, 2 weeks apart, and were killed at 4 or 8 weeks after treatment.
      Control groups were given saline. Expression of senescence-associated beta
      galactosidase was greatly induced in hepatocytes exposed to RS. In addition,
      several other changes that have been related to cell senescence were observed:
      these included markers of persistent activation of a DNA damage response, an
      increased expression of mammalian target of rapamycin, and positive regulators of
      the cell cycle, together with the induction of p21 and p27 cyclin-dependent
      kinase inhibitors. Furthermore, RS treatment increased levels of interleukin-6 in
      the liver, consistent with the activation of a senescence-associated secretory
      phenotype. CONCLUSION: These findings indicate that RS induces hepatocyte
      senescence in vivo. We propose that cell senescence and the associated secretory
      phenotype can contribute to the selective growth of transplanted hepatocytes in
      this system.

PMID- 22392701
TI  - Radiometric calibration by rank minimization.
AB  - We present a robust radiometric calibration framework that capitalizes on the
      transform invariant low-rank structure in the various types of observations, such
      as sensor irradiances recorded from a static scene with different exposure times,
      or linear structure of irradiance color mixtures around edges. We show that
      various radiometric calibration problems can be treated in a principled framework
      that uses a rank minimization approach. This framework provides a principled way
      of solving radiometric calibration problems in various settings. The proposed
      approach is evaluated using both simulation and real-world datasets and shows
      superior performance to previous approaches.

PMID- 22392700
TI  - Association of slower walking speed with incident knee osteoarthritis-related
      outcomes.
AB  - OBJECTIVE: To determine whether slower walking speed was associated with an
      increased risk of incident hip and knee osteoarthritis (OA)-related outcomes.
      METHODS: After providing informed consent, community-dwelling participants in the
      Johnston County Osteoarthritis Project completed 2 home-based interviews and an
      additional clinic visit for radiographic and physical evaluation. One thousand
      eight hundred fifty-eight noninstitutionalized residents ages >= 45 years living
      for at least 1 year in 1 of 6 townships in Johnston County, North Carolina,
      completed the study's questionnaires and clinical examinations at baseline and at
      followup testing. Walking time was assessed using a manual stopwatch in 2 trials
      over an 8-foot distance, and walking speed was calculated as the average of both
      trials. For the hip and knee, we examined 3 outcomes per joint site: radiographic
      OA (weight-bearing anteroposterior knee radiographs, supine anteroposterior
      pelvic radiographs of the hip), chronic joint symptoms, and symptomatic OA.
      Covariates included age, sex, race, education, marital status, body mass index,
      number of self-reported chronic conditions diagnosed by a health care provider,
      number of prescriptions, depressive symptoms, self-rated health, number of lower
      body functional limitations, smoking, and physical activity. RESULTS: Faster
      walking speed was consistently associated with a lower incidence of radiographic
      (adjusted odds ratio [OR] 0.88, 95% confidence interval [95% CI] 0.79-0.97) and
      symptomatic knee OA (adjusted OR 0.84, 95% CI 0.75-0.95); slower walking speed
      was associated with a greater incidence of these outcomes across a broad range of
      different clinical and radiographic OA outcomes. CONCLUSION: Slower walking speed
      may be a marker for incident knee OA, but other studies must confirm this
      finding.

PMID- 22392702
TI  - Laplacian sparse coding, Hypergraph Laplacian sparse coding, and applications.
AB  - Sparse coding exhibits good performance in many computer vision applications.
      However, due to the overcomplete codebook and the independent coding process, the
      locality and the similarity among the instances to be encoded are lost. To
      preserve such locality and similarity information, we propose a Laplacian sparse
      coding (LSc) framework. By incorporating the similarity preserving term into the
      objective of sparse coding, our proposed Laplacian sparse coding can alleviate
      the instability of sparse codes. Furthermore, we propose a Hypergraph Laplacian
      sparse coding (HLSc), which extends our Laplacian sparse coding to the case where
      the similarity among the instances defined by a hypergraph. Specifically, this
      HLSc captures the similarity among the instances within the same hyperedge
      simultaneously, and also makes the sparse codes of them be similar to each other.
      Both Laplacian sparse coding and Hypergraph Laplacian sparse coding enhance the
      robustness of sparse coding. We apply the Laplacian sparse coding to feature
      quantization in Bag-of-Words image representation, and it outperforms sparse
      coding and achieves good performance in solving the image classification problem.
      The Hypergraph Laplacian sparse coding is also successfully used to solve the
      semi-auto image tagging problem. The good performance of these applications
      demonstrates the effectiveness of our proposed formulations in locality and
      similarity preservation.

PMID- 22392703
TI  - Efficient classification for additive kernel SVMs.
AB  - We show that a class of nonlinear kernel SVMs admits approximate classifiers with
      runtime and memory complexity that is independent of the number of support
      vectors. This class of kernels, which we refer to as additive kernels, includes
      widely used kernels for histogram-based image comparison like intersection and
      chi-squared kernels. Additive kernel SVMs can offer significant improvements in
      accuracy over linear SVMs on a wide variety of tasks while having the same
      runtime, making them practical for large-scale recognition or real-time detection
      tasks. We present experiments on a variety of datasets, including the INRIA
      person, Daimler-Chrysler pedestrians, UIUC Cars, Caltech-101, MNIST, and USPS
      digits, to demonstrate the effectiveness of our method for efficient evaluation
      of SVMs with additive kernels. Since its introduction, our method has become
      integral to various state-of-the-art systems for PASCAL VOC object
      detection/image classification, ImageNet Challenge, TRECVID, etc. The techniques
      we propose can also be applied to settings where evaluation of weighted additive
      kernels is required, which include kernelized versions of PCA, LDA, regression, k
      means, as well as speeding up the inner loop of SVM classifier training
      algorithms.

PMID- 22392704
TI  - Affinity learning with diffusion on tensor product graph.
AB  - In many applications, we are given a finite set of data points sampled from a
      data manifold and represented as a graph with edge weights determined by pairwise
      similarities of the samples. Often the pairwise similarities (which are also
      called affinities) are unreliable due to noise or due to intrinsic difficulties
      in estimating similarity values of the samples. As observed in several recent
      approaches, more reliable similarities can be obtained if the original
      similarities are diffused in the context of other data points, where the context
      of each point is a set of points most similar to it. Compared to the existing
      methods, our approach differs in two main aspects. First, instead of diffusing
      the similarity information on the original graph, we propose to utilize the
      tensor product graph (TPG) obtained by the tensor product of the original graph
      with itself. Since TPG takes into account higher order information, it is not a
      surprise that we obtain more reliable similarities. However, it comes at the
      price of higher order computational complexity and storage requirement. The key
      contribution of the proposed approach is that the information propagation on TPG
      can be computed with the same computational complexity and the same amount of
      storage as the propagation on the original graph. We prove that a graph diffusion
      process on TPG is equivalent to a novel iterative algorithm on the original
      graph, which is guaranteed to converge. After its convergence we obtain new edge
      weights that can be interpreted as new, learned affinities. We stress that the
      affinities are learned in an unsupervised setting. We illustrate the benefits of
      the proposed approach for data manifolds composed of shapes, images, and image
      patches on two very different tasks of image retrieval and image segmentation.
      With learned affinities, we achieve the bull's eye retrieval score of 99.99
      percent on the MPEG-7 shape dataset, which is much higher than the state-of-the
      art algorithms. When the data- points are image patches, the NCut with the
      learned affinities not only significantly outperforms the NCut with the original
      affinities, but it also outperforms state-of-the-art image segmentation methods.

PMID- 22392705
TI  - 3D convolutional neural networks for human action recognition.
AB  - We consider the automated recognition of human actions in surveillance videos.
      Most current methods build classifiers based on complex handcrafted features
      computed from the raw inputs. Convolutional neural networks (CNNs) are a type of
      deep model that can act directly on the raw inputs. However, such models are
      currently limited to handling 2D inputs. In this paper, we develop a novel 3D CNN
      model for action recognition. This model extracts features from both the spatial
      and the temporal dimensions by performing 3D convolutions, thereby capturing the
      motion information encoded in multiple adjacent frames. The developed model
      generates multiple channels of information from the input frames, and the final
      feature representation combines information from all channels. To further boost
      the performance, we propose regularizing the outputs with high-level features and
      combining the predictions of a variety of different models. We apply the
      developed models to recognize human actions in the real-world environment of
      airport surveillance videos, and they achieve superior performance in comparison
      to baseline methods.

PMID- 22392706
TI  - Large-margin predictive latent subspace learning for multiview data analysis.
AB  - Learning salient representations of multiview data is an essential step in many
      applications such as image classification, retrieval, and annotation. Standard
      predictive methods, such as support vector machines, often directly use all the
      features available without taking into consideration the presence of distinct
      views and the resultant view dependencies, coherence, and complementarity that
      offer key insights to the semantics of the data, and are therefore offering weak
      performance and are incapable of supporting view-level analysis. This paper
      presents a statistical method to learn a predictive subspace representation
      underlying multiple views, leveraging both multiview dependencies and
      availability of supervising side-information. Our approach is based on a
      multiview latent subspace Markov network (MN) which fulfills a weak conditional
      independence assumption that multiview observations and response variables are
      conditionally independent given a set of latent variables. To learn the latent
      subspace MN, we develop a large-margin approach which jointly maximizes data
      likelihood and minimizes a prediction loss on training data. Learning and
      inference are efficiently done with a contrastive divergence method. Finally, we
      extensively evaluate the large-margin latent MN on real image and hotel review
      datasets for classification, regression, image annotation, and retrieval. Our
      results demonstrate that the large-margin approach can achieve significant
      improvements in terms of prediction performance and discovering predictive latent
      subspace representations.

PMID- 22392707
TI  - What shape are dolphins? Building 3D morphable models from 2D images.
AB  - 3D morphable models are low-dimensional parameterizations of 3D object classes
      which provide a powerful means of associating 3D geometry to 2D images. However,
      morphable models are currently generated from 3D scans, so for general object
      classes such as animals they are economically and practically infeasible. We show
      that, given a small amount of user interaction (little more than that required to
      build a conventional morphable model), there is enough information in a
      collection of 2D pictures of certain object classes to generate a full 3D
      morphable model, even in the absence of surface texture. The key restriction is
      that the object class should not be strongly articulated, and that a very rough
      rigid model should be provided as an initial estimate of the "mean shape." The
      model representation is a linear combination of subdivision surfaces, which we
      fit to image silhouettes and any identifiable key points using a novel combined
      continuous-discrete optimization strategy. Results are demonstrated on several
      natural object classes, and show that models of rather high quality can be
      obtained from this limited information.

PMID- 22392708
TI  - Online learning of correspondences between images.
AB  - We propose a novel method for iterative learning of point correspondences between
      image sequences. Points moving on surfaces in 3D space are projected into two
      images. Given a point in either view, the considered problem is to determine the
      corresponding location in the other view. The geometry and distortions of the
      projections are unknown, as is the shape of the surface. Given several pairs of
      point sets but no access to the 3D scene, correspondence mappings can be found by
      excessive global optimization or by the fundamental matrix if a perspective
      projective model is assumed. However, an iterative solution on sequences of point
      set pairs with general imaging geometry is preferable. We derive such a method
      that optimizes the mapping based on Neyman's chi-square divergence between the
      densities representing the uncertainties of the estimated and the actual
      locations. The densities are represented as channel vectors computed with a basis
      function approach. The mapping between these vectors is updated with each new
      pair of images such that fast convergence and high accuracy are achieved. The
      resulting algorithm runs in real time and is superior to state-of-the-art methods
      in terms of convergence and accuracy in a number of experiments.

PMID- 22392709
TI  - Dynamical simulation priors for human motion tracking.
AB  - We propose a simulation-based dynamical motion prior for tracking human motion
      from video in presence of physical ground-person interactions. Most tracking
      approaches to date have focused on efficient inference algorithms and/or learning
      of prior kinematic motion models; however, few can explicitly account for the
      physical plausibility of recovered motion. Here, we aim to recover physically
      plausible motion of a single articulated human subject. Toward this end, we
      propose a full-body 3D physical simulation-based prior that explicitly
      incorporates a model of human dynamics into the Bayesian filtering framework. We
      consider the motion of the subject to be generated by a feedback "control loop"
      in which Newtonian physics approximates the rigid-body motion dynamics of the
      human and the environment through the application and integration of interaction
      forces, motor forces, and gravity. Interaction forces prevent physically
      impossible hypotheses, enable more appropriate reactions to the environment
      (e.g., ground contacts), and are produced from detected human-environment
      collisions. Motor forces actuate the body, ensure that proposed pose transitions
      are physically feasible, and are generated using a motion controller. For
      efficient inference in the resulting high-dimensional state space, we utilize an
      exemplar-based control strategy that reduces the effective search space of motor
      forces. As a result, we are able to recover physically plausible motion of human
      subjects from monocular and multiview video. We show, both quantitatively and
      qualitatively, that our approach performs favorably with respect to Bayesian
      filtering methods with standard motion priors.

PMID- 22392710
TI  - Recognizing human-object interactions in still images by modeling the mutual
      context of objects and human poses.
AB  - Detecting objects in cluttered scenes and estimating articulated human body parts
      from 2D images are two challenging problems in computer vision. The difficulty is
      particularly pronounced in activities involving human-object interactions (e.g.,
      playing tennis), where the relevant objects tend to be small or only partially
      visible and the human body parts are often self-occluded. We observe, however,
      that objects and human poses can serve as mutual context to each other
      recognizing one facilitates the recognition of the other. In this paper, we
      propose a mutual context model to jointly model objects and human poses in human
      object interaction activities. In our approach, object detection provides a
      strong prior for better human pose estimation, while human pose estimation
      improves the accuracy of detecting the objects that interact with the human. On a
      six-class sports data set and a 24-class people interacting with musical
      instruments data set, we show that our mutual context model outperforms state of
      the art in detecting very difficult objects and estimating human poses, as well
      as classifying human-object interaction activities.

PMID- 22392711
TI  - Statistical Invariance for Texture Synthesis.
AB  - Estimating illumination and deformation fields on textures is essential for both
      analysis and application purposes. Traditional methods for such estimation
      usually require complicated and sometimes labor-intensive processing. In this
      paper, we propose a new perspective for this problem and suggest a novel
      statistical approach which is much simpler and more efficient. Our experiments
      show that many textures in daily life are statistically invariant in terms of
      colors and gradients. Variations of such statistics can be assumed to be
      influenced by illumination and deformation. This implies that we can inversely
      estimate the spatially varying illumination and deformation according to the
      variation of the texture statistics. This enables us to decompose a texture photo
      into an illumination field, a deformation field, and an implicit texture which
      are illumination- and deformation-free, within a short period of time, and with
      minimal user input. By processing and recombining these components, a variety of
      synthesis effects, such as exemplar preparation, texture replacement, surface
      relighting, as well as geometry modification, can be well achieved. Finally,
      convincing results are shown to demonstrate the effectiveness of the proposed
      method. 

PMID- 22392712
TI  - Live Speech Driven Head-and-Eye Motion Generators.
AB  - This paper describes a fully automated framework to generate realistic head
      motion, eye gaze, and eyelid motion simultaneously based on live (or recorded)
      speech input. Its central idea is to learn separate yet interrelated statistical
      models for each component (head motion, gaze, or eyelid motion) from a
      prerecorded facial motion data set: 1) Gaussian Mixture Models and gradient
      descent optimization algorithm are employed to generate head motion from speech
      features; 2) Nonlinear Dynamic Canonical Correlation Analysis model is used to
      synthesize eye gaze from head motion and speech features, and 3) nonnegative
      linear regression is used to model voluntary eye lid motion and log-normal
      distribution is used to describe involuntary eye blinks. Several user studies are
      conducted to evaluate the effectiveness of the proposed speech-driven head and
      eye motion generator using the well-established paired comparison methodology.
      Our evaluation results clearly show that this approach can significantly
      outperform the state-of-the-art head and eye motion generation algorithms. In
      addition, a novel mocap+video hybrid data acquisition technique is introduced to
      record high-fidelity head movement, eye gaze, and eyelid motion simultaneously. 

PMID- 22392713
TI  - Reconstructing the Curve-Skeletons of 3D Shapes Using the Visual Hull.
AB  - Curve-skeletons are the most important descriptors for shapes, capable of
      capturing in a synthetic manner the most relevant features. They are useful for
      many different applications: from shape matching and retrieval, to medical
      imaging, to animation. This has led, over the years, to the development of
      several different techniques for extraction, each trying to comply with specific
      goals. We propose a novel technique which stems from the intuition of reproducing
      what a human being does to deduce the shape of an object holding it in his or her
      hand and rotating. To accomplish this, we use the formal definitions of epipolar
      geometry and visual hull. We show how it is possible to infer the curve-skeleton
      of a broad class of 3D shapes, along with an estimation of the radii of the
      maximal inscribed balls, by gathering information about the medial axes of their
      projections on the image planes of the stereographic vision. It is definitely
      worth to point out that our method works indifferently on (even unoriented)
      polygonal meshes, voxel models, and point clouds. Moreover, it is insensitive to
      noise, pose-invariant, resolution-invariant, and robust when applied to
      incomplete data sets. 

PMID- 22392714
TI  - Conformal Magnifier: A Focus+Context Technique with Local Shape Preservation.
AB  - We present the conformal magnifier, a novel interactive focus+context
      visualization technique that magnifies a region of interest (ROI) using conformal
      mapping. Our framework supports the arbitrary shape design of magnifiers for the
      user to enlarge the ROI while globally deforming the context region without any
      cropping. By using the mathematically well-defined conformal mapping theory and
      algorithm, the ROI is magnified with local shape preservation (angle distortion
      minimization), while the transition area between the focus and context regions is
      deformed smoothly and continuously. After the selection of a specified magnifier
      shape, our system can automatically magnify the ROI in real time with full
      resolution even for large volumetric data sets. These properties are important
      for many visualization applications, especially for the computer aided detection
      and diagnosis (CAD). Our framework is suitable for diverse applications,
      including the map visualization, and volumetric visualization. Experimental
      results demonstrate the effectiveness, robustness, and efficiency of our
      framework. 

PMID- 22392715
TI  - Toward Visualization for Games: Theory, Design Space, and Patterns.
AB  - Electronic games are starting to incorporate in-game telemetry that collects data
      about player, team, and community performance on a massive scale, and as data
      begins to accumulate, so does the demand for effectively analyzing this data. In
      this paper, we use examples from both old and new games of different genres to
      explore the theory and design space of visualization for games. Drawing on these
      examples, we define a design space for this novel research topic and use it to
      formulate design patterns for how to best apply visualization technology to
      games. We then discuss the implications that this new framework will potentially
      have on the design and development of game and visualization technology in the
      future. 

PMID- 22392716
TI  - Rational BRDF.
AB  - Over the last two decades, much effort has been devoted to accurately measuring
      Bidirectional Reflectance Distribution Functions (BRDFs) of real-world materials
      and to use efficiently the resulting data for rendering. Because of their large
      size, it is difficult to use directly measured BRDFs for real-time applications,
      and fitting the most sophisticated analytical BRDF models is still a complex
      task. In this paper, we introduce Rational BRDF, a general-purpose and efficient
      representation for arbitrary BRDFs, based on Rational Functions (RFs). Using an
      adapted parametrization, we demonstrate how Rational BRDFs offer 1) a more
      compact and efficient representation using low-degree RFs, 2) an accurate fitting
      of measured materials with guaranteed control of the residual error, and 3)
      efficient importance sampling by applying the same fitting process to determine
      the inverse of the Cumulative Distribution Function (CDF) generated from the BRDF
      for use in Monte-Carlo rendering. 

PMID- 22392717
TI  - A Subdivision-Based Representation for Vector Image Editing.
AB  - Vector graphics has been employed in a wide variety of applications due to its
      scalability and editability. Editability is a high priority for artists and
      designers who wish to produce vector-based graphical content with user
      interaction. In this paper, we introduce a new vector image representation based
      on piecewise smooth subdivision surfaces, which is a simple, unified and flexible
      framework that supports a variety of operations, including shape editing, color
      editing, image stylization, and vector image processing. These operations
      effectively create novel vector graphics by reusing and altering existing image
      vectorization results. Because image vectorization yields an abstraction of the
      original raster image, controlling the level of detail of this abstraction is
      highly desirable. To this end, we design a feature-oriented vector image pyramid
      that offers multiple levels of abstraction simultaneously. Our new vector image
      representation can be rasterized efficiently using GPU-accelerated subdivision.
      Experiments indicate that our vector image representation achieves high visual
      quality and better supports editing operations than existing representations. 

PMID- 22392718
TI  - Fast Sparse Level Sets on Graphics Hardware.
AB  - The level-set method is one of the most popular techniques for capturing and
      tracking deformable interfaces. Although level sets have demonstrated great
      potential in visualization and computer graphics applications, such as surface
      editing and physically based modeling, their use for interactive simulations has
      been limited due to the high computational demands involved. In this paper, we
      address this computational challenge by leveraging the increased computing power
      of graphics processors, to achieve fast simulations based on level sets. Our
      efficient, sparse GPU level-set method is substantially faster than other state
      of-the-art, parallel approaches on both CPU and GPU hardware. We further
      investigate its performance through a method for surface reconstruction, based on
      GPU level sets. Our novel multiresolution method for surface reconstruction from
      unorganized point clouds compares favorably with recent, existing techniques and
      other parallel implementations. Finally, we point out that both level-set
      computations and rendering of level-set surfaces can be performed at interactive
      rates, even on large volumetric grids. Therefore, many applications based on
      level sets can benefit from our sparse level-set method. 

PMID- 22392719
TI  - Video Snapshots: Creating High-Quality Images from Video Clips.
AB  - We describe a unified framework for generating a single high-quality still image
      ("snapshot") from a short video clip. Our system allows the user to specify the
      desired operations for creating the output image, such as super resolution, noise
      and blur reduction, and selection of best focus. It also provides a visual
      summary of activity in the video by incorporating saliency-based objectives in
      the snapshot formation process. We show examples on a number of different video
      clips to illustrate the utility and flexibility of our system. 

PMID- 22392720
TI  - Physics-based character skinning using multidomain subspace deformations.
AB  - In this extended version of our Symposium on Computer Animation paper, we
      describe a domain-decomposition method to simulate articulated deformable
      characters entirely within a subspace framework. We have added a parallelization
      and eigendecomposition performance analysis, and several additional examples to
      the original symposium version. The method supports quasistatic and dynamic
      deformations, nonlinear kinematics and materials, and can achieve interactive
      time-stepping rates. To avoid artificial rigidity, or "locking," associated with
      coupling low-rank domain models together with hard constraints, we employ
      penaltybased coupling forces. The multidomain subspace integrator can simulate
      deformations efficiently, and exploits efficient subspace-only evaluation of
      constraint forces between rotated domains using a novel Fast Sandwich Transform
      (FST). Examples are presented for articulated characters with quasistatic and
      dynamic deformations, and interactive performance with hundreds of fully coupled
      modes. Using our method, we have observed speedups of between 3 and 4 orders of
      magnitude over full-rank, unreduced simulations.

PMID- 22392721
TI  - Female juvenile delinquency, motherhood, and the intergenerational transmission
      of aggression and antisocial behavior.
AB  - The current study explored the intergenerational transmission of aggression and
      antisocial behavior by examining mothers' juvenile delinquency, their
      pregnancies, and its impact on their children's aggressive behavior. The sample
      consisted of the first 181 biological mothers recruited as part of the Vancouver
      Longitudinal Study on the Psychosocial Development of Children (British Columbia,
      Canada). Results indicated that mothers who were juvenile delinquents were more
      likely to experience social adversity, to use substances during pregnancy and to
      offend in adulthood. Furthermore, mothers who reported juvenile delinquency had
      children who were more physically aggressive and had an earlier onset of physical
      aggression. This pattern of association held when controlling for
      sociodemographics, social adversities, prenatal substance exposure, and criminal
      involvement in adulthood. The study findings highlighted the importance of
      understanding the role and impact of female delinquency and motherhood on the
      intergenerational transmission of antisocial behavior.

PMID- 22392725
TI  - De novo design of potential RecA inhibitors using multi objective optimization.
AB  - De novo ligand design involves optimization of several ligand properties such as
      binding affinity, ligand volume, drug likeness, etc. Therefore, optimization of
      these properties independently and simultaneously seems appropriate. In this
      paper, the ligand design problem is modeled in a multiobjective using Archived
      MultiObjective Simulated Annealing (AMOSA) as the underlying search algorithm.
      The multiple objectives considered are the energy components similarity to a
      known inhibitor and a novel drug likeliness measure based on Lipinski's rule of
      five. RecA protein of Mycobacterium tuberculosis, causative agent of
      tuberculosis, is taken as the target for the drug design. To gauge the goodness
      of the results, they are compared to the outputs of LigBuilder, NEWLEAD, and
      Variable genetic algorithm (VGA). The same problem has also been modeled using a
      well-established genetic algorithm-based multiobjective optimization technique,
      Nondominated Sorting Genetic Algorithm-II (NSGA-II), to find the efficacy of
      AMOSA through comparative analysis. Results demonstrate that while some small
      molecules designed by the proposed approach are remarkably similar to the known
      inhibitors of RecA, some new ones are discovered that may be potential candidates
      for novel lead molecules against tuberculosis.

PMID- 22392726
TI  - Epigenetic regulation of vascular endothelial growth factor a dynamic expression
      in transitional cell carcinoma.
AB  - Vascular endothelial growth factor A (VEGF-A) is a key mediator in the
      neovascularization of cancers. We have found that VEGF-A was expressed at
      significantly higher levels in high-grade transitional cell carcinoma (TCC) cells
      than low-grade TCC cells in our previous study. In the present study, promoter
      methylation pattern was assessed and quantified by bisulfite genomic sequencing
      (BGS) and specific VEGF-A CpG sites in low-grade, but not in high-grade, TCC
      cells were observed. Reporter assays indicated that hypermethylation of nine CpG
      sites can inhibit the transcriptional activity of the VEGF-A gene. Subsequent
      chromatin immunoprecipitation (ChIP) assay revealed down-regulation of
      transcription activity of VEGF-A with increasing binding of methyl-CpG-binding
      protein 2 (MBD2) and trimethyl-histone H3 (Lys9) proteins to these CpG sites in
      low-grade TCC cells during hypermethylation. Furthermore, treatment of low-grade
      TCC cells with DNA methyltransferase inhibitor and histone deacetylase inhibitor
      can restore the expression of VEGF-A and promote the invasive ability of low
      grade TCC cells. Hypermethylation with lower expression levels of VEGF-A in low
      grade TCC tumors than high-grade TCC tumors was also confirmed in clinical
      specimens by reverse transcriptase-PCR and pyrosequencing analyses. Our findings
      are the first results indicating that VEGF-A expression is suppressed in low
      grade TCC tumors by promoter hypermethylation. This offers a new perspective on
      the role of VEGF-A in TCC tumor behavior.

PMID- 22392727
TI  - ESR study of the molecular orientation and dynamics of stable organic radicals
      included in the 1-D organic nanochannels of 2,4,6-tris-4-(chlorophenoxy)-1,3,5
      triazine.
AB  - The molecular orientation and dynamics of the organic stable radicals such as
      2,2,6,6-tetramethyl-1-piperidinyl-1-oxyl (TEMPO) or 4-hydroxy-TEMPO (TEMPOL)
      included in the one-dimensional (1-D) organic nanochannels of 2,4,6-tris-4
      (chlorophenoxy)-1,3,5-triazine (CLPOT) were investigated by examining the
      inclusion compounds (ICs) diluted by the co-inclusion of non-radicals using ESR
      spectroscopy. Spectral simulation showed that the axial rotation of TEMPO or
      TEMPOL molecules is excited in the nanochannels with activation energies of 8 and
      7 kJ mol(-1) , respectively. The rotation axis was estimated to be tilted towards
      the principal x direction in the axis system of the g-tensor of the respective
      radicals. This is quite different from that for similar ICs in the nanochannels
      of tris(o-phenylenedioxy)cyclotriphosphazene (TPP), in which the radicals are
      axially rotating around the principal axis y of the g-tensor. The difference is
      attributed to the larger nanospace of the CLPOT nanochannels.

PMID- 22392729
TI  - New trends in the optical and electronic applications of polymers containing
      transition-metal complexes.
AB  - Polymers containing transition-metal complexes exhibit excellent optical and
      electronic properties, which are different from those of polymers with a pure
      organic skeleton and combine the advantages of both polymers and metal complexes.
      Hence, research about this class of polymers has attracted more and more interest
      in recent years. Up to now, a number of novel polymers containing transition
      metal complexes have been exploited, and significant advances in their optical
      and electronic applications have been achieved. In this article, we summarize
      some new research trends in the applications of this important class of
      optoelectronic polymers, such as chemo/biosensors, electronic memory devices and
      photovoltaic devices.

PMID- 22392728
TI  - Histone deacetylase 6 functions as a tumor suppressor by activating c-Jun NH2
      terminal kinase-mediated beclin 1-dependent autophagic cell death in liver
      cancer.
AB  - Ubiquitin-binding histone deacetylase 6 (HDAC6) is uniquely endowed with tubulin
      deacetylase activity and plays an important role in the clearance of misfolded
      protein by autophagy. In cancer, HDAC6 has become a target for drug development
      due to its major contribution to oncogenic cell transformation. In the present
      study we show that HDAC6 expression was down-regulated in a large cohort of human
      hepatocellular carcinoma (HCC) patients, and that low expression of HDAC6 was
      significantly associated with poor prognosis of HCC patients in 5-year overall,
      disease-free, and recurrence-free survival. Notably, we observed that ectopic
      overexpression of HDAC6 suppressed tumor cell growth and proliferation in various
      liver cancer cells, and elicited increased LC3B-II conversion and autophagic
      vacuole formation without causing apoptotic cell death or cell cycle inhibition.
      In addition, the sustained overexpression of HDAC6 reduced the in vivo tumor
      growth rate in a mouse xenograft model. It was also found that HDAC6 mediated
      autophagic cell death by way of Beclin 1 and activation of the LC3-II pathway in
      liver cancer cells, and that HDAC6 overexpression activated c-Jun NH2-terminal
      kinase (JNK) and increased the phosphorylation of c-Jun. In contrast, the
      induction of Beclin 1 expression was blocked by SP600125 (a specific inhibitor of
      JNK) or by small interfering RNA directed against HDAC6. CONCLUSION: Our findings
      suggest that loss of HDAC6 expression in human HCCs and tumor suppression by
      HDAC6 occur by way of activation of caspase-independent autophagic cell death
      through the JNK/Beclin 1 pathway in liver cancer and, thus, that a novel tumor
      suppressor function mechanism involving HDAC6 may be amenable to nonepigenetic
      regulation.

PMID- 22392730
TI  - Systemic lupus erythematosus in an African Caribbean population: incidence,
      clinical manifestations, and survival in the Barbados National Lupus Registry.
AB  - OBJECTIVE: To assess the epidemiology, clinical features, and outcomes of
      systemic lupus erythematosus (SLE) in the predominantly African Caribbean
      population of Barbados. METHODS: A national registry of all patients diagnosed
      with SLE was established in 2007. Complete case ascertainment was facilitated by
      collaboration with the island's sole rheumatology service, medical practitioners,
      and the lupus advocacy group. Informed consent was required for inclusion.
      RESULTS: Between January 1, 2000 and December 31, 2009, there were 183 new cases
      of SLE (98% African Caribbean) affecting 172 women and 11 men for unadjusted
      annual incidence rates of 12.21 (95% confidence interval [95% CI] 10.46-14.18)
      and 0.84 (95% CI 0.42-1.51) per 100,000 person-years, respectively. Excluding
      pediatric cases (ages <18 years), the unadjusted incidence rate among women was
      15.14 per 100,000 person-years. The principal presenting manifestations were
      arthritis (84%), nephritis (47%), pleuritis (41.5%), malar rash (36.4%), and
      discoid lesions (33.1%). Antinuclear antibody positivity was 95%. The overall 5
      year survival rate was 79.9% (95% CI 69.6-87.1), decreasing to 68% in patients
      with nephritis. A total of 226 persons with SLE were alive at the end of the
      study for point prevalences of 152.6 (95% CI 132.8-174.5) and 10.1 (95% CI 5.4
      17.2) per 100,000 among women and men, respectively. CONCLUSION: Rates of SLE in
      Barbadian women are among the highest reported to date, with clinical
      manifestations similar to African American women and high mortality. Further
      study of this population and similar populations of West African descent might
      assist our understanding of environmental, genetic, and health care issues
      underpinning disparities in SLE.

PMID- 22392731
TI  - On the interpretation of deuterium kinetic isotope effects in C-H bond
      functionalizations by transition-metal complexes.

PMID- 22392732
TI  - Synthesis of porous PEG microgels using CaCO3 microspheres as hard templates.
AB  - Porous poly(ethylene glycol) (PEG) microgels of both 17.6 and 8.3 MUm in diameter
      are synthesized via hard templating with calcium carbonate (CaCO(3))
      microparticles. The synthesis is performed in three steps: loading of PEG
      macromonomers into CaCO(3) microparticles, crosslinking via photopolymerization,
      and removal of the CaCO(3) template under acidic conditions. The resulting porous
      PEG microgels are inverse replicates of their templates as indicated by light
      microscopy, cryo-scanning electron microscopy (cryo-SEM), and permeability
      studies. Thus this process allows for the straightforward and highly reproducible
      synthesis of porous hydrogel particles of two different diameters and porosities
      that show great potential as carriers for drugs or nanomaterials.

PMID- 22392733
TI  - A qualitative evaluation of owner and worker health and safety beliefs in small
      auto collision repair shops.
AB  - BACKGROUND: About 223,000 people are employed in approximately 34,500 auto
      collision repair businesses. In general, employees and owners in these
      establishments lack knowledge of health and safety practices and do not have the
      technical expertise to make their place of work safer. METHODS: Three employee
      and three owner focus groups were conducted. The goal of these focus groups was
      to characterize health and safety beliefs of owners and employees and to
      determine the best methods for motivating safety improvements in collision repair
      shops. RESULTS: A total of 11 owners and 19 workers participated in these focus
      groups. Employees and owners were aware of a wide range of hazards. Both groups
      noted difficulty in staying informed. Employers were hesitant to set and enforce
      safety and health rules. Employees perceive owners to be unwilling to dedicate
      the resources to make the workplace safer and provide personal protective
      equipment. Both groups felt insurance reimbursement practices placed undue
      pressure on employees. CONCLUSIONS: Focus groups provide important insights into
      intervention development in very small enterprises in general and auto collision
      shops in specific. Employers were conflicted about allowing employees a certain
      level of independence while also maintaining a safe workplace. From the employee
      perspective, owners frequently fail to provide adequate personal protective
      equipment and make improvements needed to ensure safe work. The unique managerial
      needs of very small enterprises must be accounted for if health and safety
      programs are to be implemented in these establishments.

PMID- 22392735
TI  - Five percent oxygen tension is not beneficial for neocartilage formation in
      scaffold-free cell cultures.
AB  - We have investigated whether 5% oxygen tension (O(2)) is beneficial for
      neocartilage formation when chondrocytes are cultured in transwell-COL inserts.
      Six million bovine primary chondrocytes were cultured in an insert with DMEM
      supplemented with 10% fetal bovine serum and antibiotics, with or without
      glucosamine sulphate (GS) in a 5% or 20% O(2) environment for 2, 4, or 6 weeks.
      The samples were collected for the histological staining of proteoglycans (PGs)
      and type II collagen, quantitative reverse transcription with the polymerase
      chain reaction (RT-PCR) analyses of the mRNA expression of aggrecan and
      procollagen alpha(1)(II), procollagen alpha(2)(I) and hyaluronan synthase 2,
      quantitation of PGs, and agarose gel electrophoresis. Neocartilage produced at
      20% O(2) appeared larger than that at 5% O(2). Histological staining showed that
      more PGs and type II collagen and better native cartilage structure were produced
      at 20% than at 5% O(2). The thickness of neocartilage increased during the
      culture period. Quantitative RT-PCR showed that the procollagen alpha(1)(II) mRNA
      expression level was significantly higher at 20% than at 5% O(2). However, no
      significant difference in gene expression and PG content was found between
      control and GS-treated cultures at either 20% or 5% O(2). Thus, in contrast to
      monolayer cultures, engineered cartilage from scaffold-free cultured chondrocytes
      at 20% O(2) produced better extracellular matrix (ECM) than that at 5% O(2). PGs
      were mainly large. Exogenous GS was not beneficial for the ECM in scaffold-free
      chondrocyte cultures.

PMID- 22392736
TI  - Regulation of the DLG tumor suppressor by beta-catenin.
AB  - The discs-large (DLG) tumor suppressor plays essential roles in regulating cell
      polarity and proliferation. It localizes at sites of cell-cell contact where it
      acts as a scaffold for multiple protein interactions, including with the
      adenomatous polyposis coli (APC) tumor suppressor, which in turn regulates beta
      catenin. Furthermore, many tumor types including breast and colon have increased
      levels of beta-catenin activity with correspondingly low levels of DLG
      expression. Here we provide evidence of a direct functional link between these
      apparently separate phenomena. We show that overexpressed beta-catenin can
      enhance the turnover of DLG in a proteosome dependent manner. This effect is
      specific to DLG and is not seen with two other PDZ domain-containing targets of
      beta-catenin, MAGI-1 and Scribble. Furthermore, siRNA-mediated ablation of
      endogenous beta-catenin expression also enhances DLG stability. beta-catenin
      induced degradation of DLG appears to be a consequence of a direct association
      between the two proteins and requires beta-catenin PDZ binding potential. In
      contrast, the enhanced turnover of DLG requires the unique N-terminal sequences
      and its PDZ domains. Finally, we also show that the capacity of DLG to inhibit
      transformed cell growth in an oncogene cooperation assay is inhibited by beta
      catenin. Taken together these studies suggest that one mechanism by which
      deregulated beta-catenin can contribute to tumorigenesis is through enhancing DLG
      degradation.

PMID- 22392748
TI  - [State-of-the-art devices for neuroendovascular therapy].

PMID- 22392746
TI  - Plasmonic graphene transparent conductors.
AB  - Plasmonic graphene is fabricated using thermally assisted self-assembly of silver
      nanoparticles on graphene. The localized surface-plasmonic effect is demonstrated
      with the resonance frequency shifting from 446 to 495 nm when the lateral
      dimension of the Ag nanoparticles increases from about 50 to 150 nm. Finite
      difference time-domain simulations are employed to confirm the experimentally
      observed light-scattering enhancement in the solar spectrum in plasmonic graphene
      and the decrease of both the plasmonic resonance frequency and amplitude with
      increasing graphene thickness. In addition, plasmonic graphene shows much
      improved electrical conductance by a factor of 2-4 as compared to the original
      graphene, making the plasmonic graphene a promising advanced transparent
      conductor with enhanced light scattering for thin-film optoelectronic devices.

PMID- 22392734
TI  - Axonal degeneration as a therapeutic target in the CNS.
AB  - Degeneration of the axon is an important step in the pathomechanism of traumatic,
      inflammatory and degenerative neurological diseases. Increasing evidence suggests
      that axonal degeneration occurs early in the course of these diseases and
      therefore represents a promising target for future therapeutic strategies. We
      review the evidence for axonal destruction from pathological findings and animal
      models with particular emphasis on neurodegenerative and neurotraumatic
      disorders. We discuss the basic morphological and temporal modalities of axonal
      degeneration (acute, chronic and focal axonal degeneration and Wallerian
      degeneration). Based on the mechanistic concepts, we then delineate in detail the
      major molecular mechanisms that underlie the degenerative cascade, such as
      calcium influx, axonal transport, protein aggregation and autophagy. We finally
      concentrate on putative therapeutic targets based on the mechanistic
      prerequisites.

PMID- 22392749
TI  - [Long-term outcomes of surgical treatment for epidermoid].
AB  - OBJECTIVE: Surgical strategies for epidermoids in our department is that the
      tumor capsule and surrounding arachnoid membrane should be sharply dissected and
      resected as much as possible. However, if total resection is not possible,
      because of the danger of surgical morbidity, partial resection should be carried
      out. The present study reports on long-term outcomes of surgical treatment for
      intracranial epidermoid in our department. METHODS: Since 1994, intracranial
      epidermoids have been resected in 13 patients in our department. The mean age at
      the time of surgery was 50.2 years and the mean postoperative follow-up period
      was 75.8 months. Surgical outcome, postoperative morbidity, Karnofsky Performance
      Status (KPS) during long-term follow-up, hydrocephalus, and regrowth rate were
      investigated. RESULTS: Among the 13 patients, 5 underwent total resection, 5
      subtotal resection, and 3 partial resection. No permanent morbidity occurred and
      KPS did not worsen postoperatively in any of the patients. Surgery for
      hydrocephalus was performed in 3 patients. However, hydrocephalus had been
      suspected before surgery in each patient. Regrowth occurred in 1 patient, showing
      malignant transformation 1 year after total resection. No regrowth during long
      term follow-up was observed in the other 12 patients, and none showed
      exacerbation of KPS. CONCLUSION: The present study indicates that regrowth does
      not necessarily occur in patients with epidermoids. Although total resection is
      ideal, to avoid any surgical morbidity is even more important. Partial resection
      should be performed if total resection is impossible.

PMID- 22392750
TI  - [Operated case of a ruptured aneurysm arising from fenestration of the vertebral
      artery].
AB  - Aneurysm arising from duplication of the vertebral artery (VA) is rare. We report
      a surgical case of an aneurysm of VA fenestration and provide a literature
      review. A 42-year-old man suffered from sudden onset of severe headache. CT image
      revealed subarachnoid hemorrhage predominantly in the posterior fossa. Digital
      subtraction angiography showed a fenestration of the right VA and the aneurysm
      arising from the proximal limb of the fenestration. Neck clipping of the aneurysm
      was performed because embolization was difficult due to the wide neck. The
      patient was discharged without deficits. Seven cases of an aneurysm of the VA
      fenestration have been reported. Five cases underwent coil embolization, and 2
      underwent craniotomy, trapping, and resection. This is the first case of neck
      clipping of an aneurysm of the VA fenestration.

PMID- 22392751
TI  - [Case of surgical treatment for giant hemangioblastoma in the dorsal medulla
      oblongata].
AB  - Hemangioblastoma in the medulla oblongata is a relatively rare tumor. We present
      the case of a giant hemangioblastoma occurring in the dorsal medulla oblongata. A
      33-year-old man with no neurological symptoms was diagnosed with a
      hemangioblastoma in the dorsal medulla oblongata, and opted for observation in
      the outpatient department. After 22 months of observation time, MRI scans showed
      rapid local tumor progression and obstructive hydrocephalus. At this point, he
      presented with mild dysphagia as a preoperative neurological deficit. Total
      surgical removal of the tumor was performed after temporary ventricle drainage
      and preoperative embolization of the feeding artery. Postoperatively, he became
      fully conscious but developed bulbar palsy followed by tracheostomy. During the
      12 months of postoperative follow-up, severe dysphagia was still present.

PMID- 22392752
TI  - [Case of direct carotid-cavernous fistula presenting with subarachnoid
      hemorrhage].
AB  - We report a case of longstanding asymptomatic direct carotid-cavernous fistula
      (CCF) which caused fatal subarachnoid hemorrhage (SAH). A 91-year-old female with
      no history of previous head trauma and optic symptoms presented acute
      subarachnoid hemorrhage. Angiography revealed a left direct carotid-cavernous
      fistula draining only into the contralateral cavernous sinus with leptomeningeal
      venous reflux and small varix on the pontine bridging vein. The affected
      cavernous sinus was markedly dilated and there was no septum between the left
      cavernous sinus and the internal carotid artery. The patient underwent
      transvenous coil embolization for intercavernous sinus and leptomeningeal venous
      reflux was successfully obliterated and opacification of the varix was
      diminished. The past history of this patient and angiographical findings strongly
      suggest long standing asymptomatic CCF caused SAH.

PMID- 22392753
TI  - [Migration of the distal catheter of ventriculo-peritoneal shunt into the
      thoracic cavity].
AB  - A 69-year-old woman suffered from ataxia of her right upper and lower limbs and
      infection in a distal tube of a ventriculo-peritoneal shunt (VPS). She had a
      thirty-year history of treatment for intracranial hemangioblastoma due to von
      Hippel-Lindau disease and hydrocephalus. Head magnetic resonance imaging
      demonstrated recurrent multiple hemangioblastoma in the cerebellum without
      hydrocephalus. Chest computed tomography showed a migrated distal tube of a VPS
      into the thoracic cavity. The VPS had been revised several times because of
      repeated infection before the present admission. The hydrocephalus was considered
      to be independent on the VPS because the VPS had become obstructed. A pleural
      effusion, which was probably caused by hypoalbuminemia during the postoperative
      course of the hemangioblastoma, increased and disappeared in association with her
      postoperative nutritional status. Therefore, revision of the migrated distal
      catheter was not needed. The distal tube most likely migrated through the
      intercostal space because the patient was very skinny. Migration of the distal
      catheter of VPS into the thoracic cavity may occur when the course of the distal
      tube is close to the thoracic cavity, especially in thin patients. Care should be
      taken when routing the distal catheter after VPS in skinny patients.

PMID- 22392754
TI  - [Relapsing polychondritis presenting as encephalitis].
AB  - Relapsing polychondritis (RP) is a rare, generalized autoimmune disorder that is
      characterized by recurrent inflammation of various cartilaginous structures.
      Involvement of the central nervous system is rarely observed in RP. Here we
      report a case of encephalitis associated with RP. A 60-year-old man presented
      with headache and bilateral ear swelling. Three weeks later, he came to our
      hospital because of the acute onset of a speech impediment. A non-contrast
      computed tomography scan of the head showed slight high-density areas in his left
      frontal lobe, but he refused to be admitted and went home. On the next day, he
      developed acalculia, agraphia, right-left disorientation, and mild right
      hemiparesis. Brain MRI revealed hyperintensity areas in the left frontal sulcus
      on fluid-attenuated inversion recovery (FLAIR) images, and these hyperintensity
      areas were enhanced by gadolinium. Therefore, the patient's symptoms were
      diagnosed as focal epilepsy caused by meningoencephalitis. Other examinations,
      including laboratory blood tests, cerebrospinal fluid tests, and a cerebral
      angiography, were all negative. Therefore, a brain biopsy of the left frontal
      cortex was performed 5 days after the patient's admission. Pathological findings
      revealed chronic inflammation of the meninges, so prednisone was administered.
      After receiving oral prednisone, the patient's bilateral ear swelling
      dramatically improved and the lesions apparent on cranial MRI gradually subsided.
      The patient was diagnosed with RP by a neurologist after discharge from the
      hospital. In this study, early diagnosis and steroid treatment is recommended for
      patients with neurological complications due to RP.

PMID- 22392755
TI  - [Case of a giant cervical carotid artery aneurysm with contralateral severe
      stenosis treated using a covered stent].
AB  - We report a case of a cervical carotid artery pseudoaneurysm with contralateral
      severe stenosis, treated using a covered stent. A 79-year-old man admitted for a
      splenic artery aneurysm presented a pulsatile mass on the right side of his neck
      and lower cranial nerve palsy after misinsertion of a central venous line into
      the right carotid artery. MRI revealed a huge thrombosed aneurysm (30 mm*25 mm)
      in the right common carotid artery (CCA). We planned an aneurysmectomy and CCA
      interposition with a vascular graft. However the aneurysm continued to expand. We
      considered that it was difficult to expose the internal carotid artery (ICA) by a
      direct surgical technique, and therefore carried out placement of a covered stent
      over the orifice of the aneurysm using an endovascular surgical technique.
      Following placement of the covered stent, subsequent contrast-enhanced CT
      revealed leakage of contrast material into the aneurysm. An additional bare stent
      was placed into the proximal end of the covered stent at 15 days after the
      initial treatment. Angiography demonstrated no leakage of the contrast material.
      Following the second treatment, the pulsatile mass was reduced in size. Lower
      cranial nerve palsy remained but had slightly improved. We described the case of
      a huge cervical carotid pseudoaneurysm that was successfully treated using a
      covered stent.

PMID- 22392756
TI  - [Case of metastatic malignant melanoma detected by multifocal cerebral
      hemorrhage].
AB  - We encountered a case of intracranial metastatic malignant melanoma which caused
      repeated multiple hemorrhage. Intracranial metastatic malignant melanoma showed
      high intensity in the magnetic resonance imaging's T1 weighted image, low
      intensity in T2 weighted image and very low intensity in T2* weighted image.
      Positron emission tomographic scans are useful for systemic evaluation of active
      malignancies. The present case underwent tumor removal following re-bleeding. The
      patient died of repeated hemorrhage one month after the operation. Intracranial
      metastatic malignant melanoma has a strong propensity to cause intracerebral
      hemorrhage leading to clinical deterioration. We think that the development of a
      therapeutic strategy for the treatment of intracranial metastatic malignant
      melanoma, including its risk management of intracerebral hemorrhage would be
      great importance.

PMID- 22392757
TI  - [Case of an internal carotid artery aneurysm complicated with coil protrusion
      during embolization].
AB  - Coil migration during cerebral aneurysm embolization is rare, but one of the most
      troublesome events. A 65-year-old woman was referred to our hospital for the
      treatment of a cerebral aneurysm. Angiography showed the aneurysm at the C3
      portion of the right internal carotid artery. The neck of the aneurysm was wide.
      A detachable coil was placed into the aneurysm using the balloon neck plasty
      technique and was detached after confirmation of its stability. However, after
      detachment, the coil started to migrate. The balloon was inflated to prevent coil
      migration and another coil was inserted into the aneurysm to stabilize the
      migrated coil. Finally, the aneurysm was subtotally embolized with 9 coils. The
      postoperative course was uneventful. Coil migration may occur especially in a
      wide-neck aneurysm. Appropriate coil selection is important to prevent such
      migration. Subsequent coil insertion, retrieval of the migrated coil, and stent
      placement are the treatment options for coil migration.

PMID- 22392759
TI  - Poly(1,2,4-oxadiazolidin-5-one)s synthesized by polycycloaddition of
      bisoxaziridines and diisocyanate.
AB  - A premier in polymer chemistry: the cycloaddition of bisoxaziridines with 4,4'
      methylene diphenyl diisocyanate yields novel linear poly(1,2,4-oxadiazolidin-5
      one) derivatives. The polymers are relatively stable (>200  degrees C) and model
      reactions show that the reaction rate strongly depends on the electronic
      properties of the oxaziridine unit; electron-donating substituents on the C atom
      of the heterocyclic ring promote the cycloaddition.

PMID- 22392758
TI  - Evaluation of patient dose and operator dose in swallowing CT studies performed
      with a 320-detector-row multislice CT scanner.
AB  - Recently, attempts to develop new types of swallowing function analysis with 320
      detector-row multislice CT (320-MDCT) have been reported. The present report
      addresses (1) patient exposure, (2) operator exposure, and (3) spatial dose
      distribution. For dose measurement, a human-body phantom in which 303
      thermoluminescent dosimeter elements were inserted and a survey meter was used.
      The patient position was confirmed with a single-volume scan at a tube voltage of
      120 kV, a tube current of 10 mA, a rotation speed of 0.35 s/rot., a slice
      thickness of 0.5 mm, coverage of 160 mm, a scan field of view of 240 mm, a small
      focal spot size, and a gantry tilt angle of 22 degrees  (volume CT dose index
      displayed on the console 0.8 mGy, dose-length product 12.1 mGy cm). The effective
      dose for the patient in swallowing CT (SCT) was 3.9 mSv. The conversion factor
      for obtaining the effective dose was 0.0066 mSv/mGy cm. The effective dose for
      the operator was 0.002 mSv. In the operator exposure measurement, the ambient
      dose equivalent H*(10), that would be produced by an expanded and aligned
      radiation field at a depth 10 mm in the International Commission on Radiation
      Units and Measurements sphere, was 0.012 mSv. In this report, the safety of SCT,
      which has become possible with the introduction of 320-MDCT, was evaluated by
      measurement of the exposure to the patient and operator.

PMID- 22392760
TI  - Polyelectrolyte capsules as carriers for growth factor inhibitor delivery to
      hepatocellular carcinoma.
AB  - The efficient internalization of TGF-beta inhibitor-loaded polyelectrolyte
      capsules and particles is studied in two HCC cell lines. Two polyelectrolyte
      pairs (biocompatible but not degradable and biodegradable crosslinked with
      gluteraldehyde) are employed for coating. The capsules are characterized by SEM.
      LY is successfully loaded inside the core and embedded between polymer layers. MS
      is used to quantify the loading efficiency by comparing post-loading and core
      loading methods, since both coated templates and hollow shells are used as
      carriers. CLSM confirms dissolution of the pre-formed multilayer upon enzymatic
      degradation as the method of release, and migration assays demonstrate a higher
      inhibition efficiency of TGF-beta in tailored biodegradable capsules compared to
      free LY administration.

PMID- 22392761
TI  - High magnetic field solid-state NMR analyses by combining MAS, MQ-MAS, homo
      nuclear and hetero-nuclear correlation experiments.
AB  - A general strategy of structural analysis of alumina silicate by combining
      various solid-state NMR measurements such as single pulse, multi-quantum magic
      angle spinning, double-quantum homo-nuclear correlation under magic angle
      spinning (DQ-MAS), and cross-polarization hetero-nuclear correlation (CP-HETCOR)
      was evaluated with the aid of high magnetic field NMR (800 MHz for (1) H Larmor
      frequency) by using anorthite as a model material. The high magnetic field
      greatly enhanced resolution of (27) Al in single pulse, DQ-MAS, and even in
      triple-quantum magic angle spinning NMR spectra. The spatial proximities through
      dipolar couplings were probed by the DQ-MAS methods for homo-nuclear correlations
      between both (27) Al-(27) Al and (29) Si-(29) Si and by CP-HETCOR for hetero
      nuclear correlations between (27) Al-(29) Si in the anorthite framework. By
      combining various NMR methodologies, we elucidated detailed spatial correlations
      among various aluminum and silicon species in anorthite that was hard to be
      determined using conventional analytical methods at low magnetic field. Moreover,
      the presented approach is applicable to analyze other alumina-silicate minerals.

PMID- 22392762
TI  - Effects of pulse versus steady recruitment on sessile marine communities.
AB  - Variation in patterns of propagule establishment (recruitment) has important
      effects on population dynamics and the structure of some communities. Most
      experimental studies have varied recruitment by changing the nature of a single
      event early in community development, but recruitment can also vary from steady
      rates of arrival to highly episodic 'pulse' events, causing differences in the
      temporal spacing of individuals recruiting into patches. We examined whether two
      different temporal patterns of recruitment of sessile invertebrates affected
      temperate marine communities in southeastern Australia in two experiments that
      were run at different times at the same site and that manipulated several
      different species. Target species entered communities as either a single pulse of
      recruits within a 2-week period or steady input of the same total number of
      recruits over a longer time period (5-6 weeks). The pattern of recruitment had
      variable effects on community structure. The colonial ascidian Botryllus
      schlosseri did not have a strong influence on community structure whether it
      recruited in a single pulse or steadily. The cover of B. schlosseri was higher
      when recruitment occurred as a single pulse. In a second experiment, botryllid
      ascidians caused changes in the composition of communities when they recruited
      steadily compared to when they did not recruit or didemnids recruited, but caused
      no differences in communities when they recruited in a shorter pulse. In
      contrast, recruitment frequency of didemnid ascidians had little effect, though
      their presence/absence caused community differences. Though we found that
      different temporal recruitment patterns can alter community composition, the life
      history and ecology of particular taxa as well as differences in environmental
      background processes are likely to influence the strength of these effects.

PMID- 22392763
TI  - Plasticity in habitat use determines metabolic response of fish to global warming
      in stratified lakes.
AB  - We used a coupled lake physics and bioenergetics-based foraging model to evaluate
      how the plasticity in habitat use modifies the seasonal metabolic response of two
      sympatric cold-water fishes (vendace and Fontane cisco, Coregonus spp.) under a
      global warming scenario for the year 2100. In different simulations, the
      vertically migrating species performed either a plastic strategy (behavioral
      thermoregulation) by shifting their population depth at night to maintain the
      temperatures occupied at current in-situ observations, or a fixed strategy (no
      thermoregulation) by keeping their occupied depths at night but facing modified
      temperatures. The lake physics model predicted higher temperatures above 20 m and
      lower temperatures below 20 m in response to warming. Using temperature
      zooplankton relationships, the density of zooplankton prey was predicted to
      increase at the surface, but to decrease in hypolimnetic waters. Simulating the
      fixed strategy, growth was enhanced only for the deeper-living cisco due to the
      shift in thermal regime at about 20 m. In contrast, simulating the plastic
      strategy, individual growth of cisco and young vendace was predicted to increase
      compared to growth currently observed in the lake. Only growth rates of older
      vendace are reduced under future global warming scenarios irrespective of the
      behavioral strategy. However, performing behavioral thermoregulation would drive
      both species into the same depth layers, and hence will erode vertical
      microhabitat segregation and intensify inter-specific competition between the
      coexisting coregonids.

PMID- 22392764
TI  - Grazing-induced effects on soil properties modify plant competitive interactions
      in semi-natural mountain grasslands.
AB  - Plant-soil feedbacks are widely recognized as playing a significant role in
      structuring plant communities through their effects on plant-plant interactions.
      However, the question of whether plant-soil feedbacks can be indirectly driven by
      other ecological agents, such as large herbivores, which are known to strongly
      modify plant community structure and soil properties, remains poorly explored. We
      tested in a glasshouse experiment how changes in soil properties resulting from
      long-term sheep grazing affect competitive interactions (intra- and inter
      specific) of two graminoid species: Nardus stricta, which is typically abundant
      under high sheep grazing pressure in British mountain grasslands; and Eriophorum
      vaginatum, whose abundance is typically diminished under grazing. Both species
      were grown in monocultures and mixtures at different densities in soils taken
      from adjacent grazed and ungrazed mountain grassland in the Yorkshire Dales,
      northern England. Nardus stricta performed better (shoot and root biomass) when
      grown in grazing-conditioned soil, independent of whether or not it grew under
      inter-specific competition. Eriophorum vaginatum also grew better when planted in
      soil from the grazed site, but this occurred only when it did not experience
      inter-specific competition with N. stricta. This indicates that plant-soil
      feedback for E. vaginatum is dependent on the presence of an inter-specific
      competitor. A yield density model showed that indirect effects of grazing
      increased the intensity of intra-specific competition in both species in
      comparison with ungrazed-conditioned soil. However, indirect effects of grazing
      on the intensity of inter-specific competition were species-specific favouring N.
      stricta. We explain these asymmetric grazing-induced effects on competition on
      the basis of traits of the superior competitor and grazing effects on soil
      nutrients. Finally, we discuss the relevance of our findings for plant community
      dynamics in grazed, semi-natural grasslands.

PMID- 22392767
TI  - Molecularly imprinted shells from polymer and xerogel matrices on polystyrene
      colloidal spheres.
AB  - We have devised a facile and general methodology for the synthesis of various
      molecularly imprinted shells at the surface of polystyrene (PS) colloidal spheres
      to recognize the explosive compound 2,4,6-trinitrotoluene (TNT). PS spheres with
      surface-functionalized carboxyl-group layers could direct a selective imprinting
      polymerization on their surface through the hydrogen-bonding interactions between
      surface carboxyl groups and amino monomers. Meanwhile, homogeneous polymerization
      in the solution phase was completely prevented by stepwise polymerization. The
      overall process led to the formation of monodisperse molecularly imprinted core
      shell microspheres, and was very successful in the preparation of organic polymer
      and inorganic xerogel shells. Furthermore, greater capacity and faster binding
      kinetics towards target species were achieved, because surface-imprinted sites
      ensured the complete removal of templates, good accessibility to target
      molecules, and low mass-transfer resistance. The results reported herein,
      concerning the production of high-quality molecularly imprinted products, could
      also form the basis for the formulation of a new strategy for the fabrication of
      various functional coating layers on colloidal spheres with potential
      applications in the fields of separations and chemical sensing.

PMID- 22392766
TI  - Decision tool to improve the quality of care in rheumatoid arthritis.
AB  - OBJECTIVE: Despite the importance of achieving tight control, many patients with
      rheumatoid arthritis (RA) are not effectively treated with disease-modifying
      antirheumatic drugs. The objective of this study was to develop a decision
      support tool to inform RA patients with ongoing active disease about the risks
      and benefits related to biologic therapy. METHODS: We developed a balanced, web
      based, decision support tool. Options, values, and probabilistic information were
      described using theoretically supported formulations. We conducted a pre
      /posttest study to assess preliminary evidence of the tool's efficacy in
      improving knowledge related to biologics, clarity of values, willingness to take
      a biologic, and informed choice. RESULTS: We interviewed 104 subjects (mean age
      62 years, 84% women, 87% white, and median duration of RA 8 years). Knowledge
      (coded on a 0-20 scale) and willingness to take a biologic (coded on a 0-10
      scale) significantly increased after viewing the tool (mean differences 2.3 and
      1.4, respectively; P < 0.0001 for both). Perceived knowledge and values clarity
      (coded on 0-100 scales) also significantly improved (mean differences 20.4 and
      20.8, respectively; P < 0.0001 for both). The proportion of subjects making an
      informed value-concordant choice increased substantially from 35% to 64%.
      CONCLUSION: A tool designed to effectively communicate the risks and benefits
      associated with biologic therapy increased knowledge, patient willingness to
      escalate care, and the likelihood of making an informed choice. The results of
      this study support the need for a clinical trial to examine the impact of the
      tool in clinical practice.

PMID- 22392765
TI  - Targeting Mnks for cancer therapy.
AB  - Deregulation of protein synthesis is a common event in human cancer and a key
      player in translational control is eIF4E. Elevated expression levels of eIF4E
      promote cancer development and progression. Recent findings suggest that eIF4E
      activity is a key determinant of the PI3K/Akt/mTOR and Ras/Raf/MEK/ERK mediated
      tumorigenic activity and targeting eIF4E should have a major impact on these
      pathways in human cancer. The function of eIF4E is modulated through
      phosphorylation of a conserved serine (Ser209) by Mnk1 and Mnk2 downstream of
      ERK. While the phosphorylation event is necessary for oncogenic transformation,
      it seems to be dispensable for normal development. Hence, pharmacologic Mnk
      inhibitors may provide non-toxic and effective anti-cancer strategy. Strong
      circumstantial evidence indicates that Mnk inhibition presents attractive
      therapeutic potential, but the lack of selective Mnk inhibitors has so far
      confounded pharmacological target validation and clinical development.

PMID- 22392768
TI  - Salivary secretions from the ectoparasitic wasp, Eulophus pennicornis contain
      hydrolases, and kill host hemocytes by apoptosis.
AB  - The current work demonstrates that larvae of the ectoparasitic wasp, Eulophus
      pennicornis, produce salivary secretions (Ep S) that contain a variety of
      hydrolases. This includes medium to high levels of N-acetyl-beta-glucosaminidase
      activity, relatively low levels of esterase (C 4) and lipase (C 14) activity, and
      trace levels of esterase lipase (C 8), acid phosphatise, beta-galactosidase, beta
      glucuronidase, and alpha-glucosidase activity. In addition, in vitro monolayer
      assays indicate that both a 4 h and an 18 h incubation of hemocytes from host
      Lacanobia oleracea larvae in Ep S significantly increases (P < 0.001) the
      percentage of cells dying by apoptosis compared to the controls. Moreover, an 18
      h incubation of hemocytes in Ep S (but not a 4 h incubation), also significantly
      increased the percentage of dead cells detected using a trypan-blue exclusion
      assay. The role of ectoparasitoid salivary secretions in conditioning the host by
      disabling hemocyte-mediated wound healing responses, and providing food for the
      developing wasp larvae is discussed.

PMID- 22392769
TI  - RNA interference of two acetylcholinesterase genes in Plutella xylostella reveals
      their different functions.
AB  - Acetylcholinesterase (AChE, EC 3.1.1.7) is an important enzyme with a typical
      function of degrading the neurotransmitter acetylcholine. Although two ace genes
      were reported in Plutella xylostella, their function differences remain largely
      unknown. The chemically synthesized siRNAs (si-Pxace1 and si-Pxace2) were
      injected into the second instar larvae to knock down Pxace1 and Pxace2, either
      respectively or simultaneously. The mRNA abundance of Pxace1 and Pxace2 was
      significantly reduced to 7-33.5% of the control levels at 72 h after siRNA
      injection. The AChE activities were significantly decreased at 96 h after
      treatment. Silencing of Pxace1 or Pxace2 resulted in mortality of 33.9 and 22.9%,
      respectively. The survivors in siRNA-treated groups had apparent growth
      inhibition such as reduction in larvae weights and lengths, malformation and
      motor retardation. Knockdown of Pxace1 apparently affected more on larvae growth
      than that of Pxace2, suggesting that Pxace1 had more important roles than Pxace2.
      Both Pxace1 and Pxace2 genes might have atypical functions in regulating larvae
      growth and motor ability.

PMID- 22392770
TI  - Annotation and evolution of the antioxidant genes in the silkworm, Bombyx mori.
AB  - Antioxidant system, which is composed of multiple gene families, plays a major
      role in reducing oxidative damage and xenobiotic detoxification in all living
      organisms. We identified 50 silkworm antioxidant genes from nine gene families
      based on the assembled genome sequence. A comparative analysis of the antioxidant
      genes of the silkworm with other order insects Anopheles gambiae, Apis mellifera,
      Drosophila melanogaster, and Tribolium castaneum, was performed. We found that
      most of the antioxidant gene families are highly conserved but Catalase (CAT) and
      heme-containing peroxidase (HPX) families were lineage-specifically expanded in
      the silkworm. The expression patterns of the silkworm antioxidant genes were
      investigated with the known ESTs, microarray data, and reverse transcription
      polymerase chain reaction (RT-PCR). Forty two of the 50 silkworm antioxidant
      genes were transcribed and most of the transcribed genes showed tissue-specific
      expression patterns. More than a half of lineage-specifically expanded BmCATs
      lacked 15 or more than 15 of the 36 heme-binding residues and might lose catalase
      activities. However, the genes encoding these BmCATs showed almost a ubiquitous
      tissue expression pattern, indicating that they might have evolved new functions.
      In addition, the lineage-specifically expanded BmHPXs could function in
      maintaining cell homeostasis in the process of the synthesis of large amounts of
      silk proteins because they were predominantly expressed in silk gland of the
      silkworm. The lineage-specific expansion of antioxidant gene families in the
      silkworm provides useful information for understanding evolution and functional
      versatility of antioxidant genes in the silkworm even Lepidopteran insects.

PMID- 22392771
TI  - Characterization of glucose-induced glucose oxidase gene and protein expression
      in Helicoverpa armigera larvae.
AB  - Caterpillar labial salivary enzyme glucose oxidase (GOX) plays an important role
      in plant-insect interactions by suppressing the caterpillar-induced nicotine
      production in tobacco plants. In the present study, we cloned and characterized
      the GOX gene (HaGox) from labial salivary glands of Helicoverpa armigera larvae
      using 3' and 5' RACE, homologous analysis, phylogenetic analysis, LC-MS/MS, and
      qRT-PCR. The deduced GOX amino acid sequence (606 amino acids) shares 99% and 76%
      identity with H. zea and Spodoptera exigua GOX, respectively, and is consistent
      with the GOX protein sequence identified from H. armigera labial salivary gland.
      These results confirmed that the HaGox encode the GOX protein. Transcript levels
      of HaGox in larval labial salivary glands were significantly higher than those in
      midgut and hemolymph, respectively, and those of caterpillars reared on tobacco
      leaves coated with 0.1%, 1%, and 10% glucose solutions were significantly higher
      than those reared on 0.01% glucose-coated leaves or control tobacco leaves.
      Western blot and native PAGE showed that GOX protein expression levels and GOX
      enzymatic activities also increased with dietary glucose. These results proved
      that GOX expressions in larval labial salivary glands induced by dietary glucose
      were exhibited not only on transcriptional levels, but also on
      translational/posttranslational levels.

PMID- 22392772
TI  - Caged glutathione - triggering protein interaction by light.
AB  - Light, GSH, action! Glutathione (GSH) fulfills a universal role as redox factor,
      scavenger of reactive oxygen species, and as an essential substrate in the
      conjugation, detoxification, and reduction reactions catalyzed by glutathione S
      transferase (GST). A photoactivatable glutathione allows the GSH-GST network to
      be triggered by light. GST fusion proteins can be assembled in situ at variable
      density and structures by laser-scanning activation.

PMID- 22392773
TI  - Antidepressants to cancer patients during the last year of life--a population
      based study.
AB  - OBJECTIVE: Although depression is common among incurable cancer patients, the
      prescription prevalence of antidepressants (ADs) to these patients is largely
      unknown. Aims were to examine the prescription prevalence of ADs in the last year
      of life in a 2-year national cancer death cohort and to examine its associations
      with sociodemographic and medical variables. METHODS: Nationwide, 20,627 cancer
      deaths in adults were identified by combining the Norwegian Central Population
      and Cancer Registries. Individual prescriptions of ADs in the 12 months prior to
      death were identified in the Norwegian Prescription Database. The study
      population consisted of 17,753 patients who died from cancer in 2005 and 2006,
      after excluding patients assumed to be hospitalized whose prescriptions were not
      registered in the Norwegian Prescription Database. RESULTS: Twenty-two percent (N
      = 3836) had at least one prescription of ADs in their last year of life (men
      19%/women 25%), compared with 6% in the general population (men 4%/women 8%).
      Patients who died within 1 year from diagnosis had lower prescription prevalence
      (20%) than patients with longer disease duration (23%) (p < 0.001). Prescription
      prevalence increased toward death for both genders, but the prevalence of first
      time prescriptions in the last 6 months of life was similar across genders. About
      10% of ADs were prescribed for the first time 30 days or less before death.
      CONCLUSION: The prescription prevalence among cancer patients in the last year of
      life was almost four times higher than in the general population. One of 10
      patients was prescribed with ADs so close to death that the clinical effects can
      be questioned.

PMID- 22392774
TI  - Focused actions to protect carbon nanotube workers.
AB  - There is still uncertainty about the potential health hazards of carbon nanotubes
      (CNTs) particularly involving carcinogenicity. However, the evidence is growing
      that some types of CNTs and nanofibers may have carcinogenic properties. The
      critical question is that while the carcinogenic potential of CNTs is being
      further investigated, what steps should be taken to protect workers who face
      exposure to CNTs, current and future, if CNTs are ultimately found to be
      carcinogenic? This paper addresses five areas to help focus action to protect
      workers: (i) review of the current evidence on the carcinogenic potential of
      CNTs; (ii) role of physical and chemical properties related to cancer
      development; (iii) CNT doses associated with genotoxicity in vitro and in vivo;
      (iv) workplace exposures to CNT; and (v) specific risk management actions needed
      to protect workers.

PMID- 22392775
TI  - [Study of female predilection for thyroid gland carcinoma in Republic Armenia].
AB  - Thyroid carcinoma is the most common primary cancer of the thyroid gland. The
      purpose of the study is to find if thyroid gland carcinoma show gender
      predilection in Armenia. 529 cases of thyroid gland cancer were studied in
      hospitals from 1999 to 2011. It was found that thyroid gland carcinoma is three
      times more common in women than in men practically in all age groups. In
      comparison with 1985 year the frequency of disease in women has increased.
      Thyroid gland carcinoma had a higher death rate in women than in men. The
      lethality was higher in men.

PMID- 22392776
TI  - [Problem of early intra- and preoperative pathomorphologic diagnosis of thyroid
      cancer].
AB  - Thyroid cancer is considered as one of the deadly cancers. Differentiation of
      benign and malignant structures is difficult in patients with thyroid cancer.
      This work is devoted to the problem of early clinical diagnosis of thyroid
      cancer. 523 cases of primary thyroid cancer from 1999 to 2011 were studied.  The
      pathomorphologic analysis of thyroid cancer was carried out. The problem of early
      detection of thyroid cancer is reviewed. It is concluded that the thyroid nodule
      fine-needle aspirate biopsy and intraoperative frozen section examination do not
      allow the accurate differentiation of benign tumours from malignant neoplasms;
      novel diagnostic methods for early detection of thyroid cancer are needed.

PMID- 22392777
TI  - [Postradiotherapy complications and their correction ways at patients with
      nasopharyngeal carcinoma].
AB  - Today hyperfractionated radiotherapy in combination with cisplatin and 5-FU is
      the most effective treatment modality of patients with nasopharyngeal carcinoma.
      However late complications of this method are investigated poorly what was the
      aim of this research.   Analyzing treatment results of 118 patients who achieved
      complete tumor regression we revealed that radiation damages more often and
      severe at patients who received more aggressive treatment - accelerated
      hyperfractionated radiotherapy with and without concurrent cytotoxic drugs. But
      application of complex prophylaxis and treatment measures by radiation
      oncologists in cooperation with other specialist (stomatologists, dermatologists,
      endocrinologists etc.) allow to control toxicity and finalize planned treatment
      schedule.

PMID- 22392778
TI  - [Impact of new technologies on the rheological properties of blood in plastic
      surgery of the breast].
AB  - 151 patients were examined undergoing breast reconstruction. In all patients
      after surgery were studied rheology and acid ground state of the blood. Of these
      71 patients was performed ozone therapy. This use ozone therapy helps oxygen
      supple of tissues, a significant decrease in lymphostasis upper limb, increases
      the oxygen tension in the tissues and blood, normalizes blood flow, more rapidly
      restores blood lymph and is the prevention postoperative complications. Frequency
      of early postoperative complications decreased 2,5 times the number of necrotic
      autotransplantate--5 times compared with patients who are in post-operative fluid
      therapy did not include ozone-oxygenated crystalloid solutions.

PMID- 22392779
TI  - [Features of physical and sexual development and reproductive behaviour in female
      adolescents].
AB  - Assessment of adolescent's reproductive behaviour, identification of the factors
      affecting this kind of behavior, represented the main goal of the study. 
      Comprehensive examination (n=136) and interviewing (n=825) was made in female
      adolescents aged 14 to 19 years (randomly formed via continuous selection). 
      Information of the state of their health, their attitude towards child - bearing
      and their risky habits have been evaluated. Under the present conditions, the
      development of the reproductive system in female adolescents is characterized by
      the high frequency of menstrual irregulates (24,7%), the delayed formation of the
      bone pelvis (25,2%) the trend for retarted development of secondary sexual
      characters (12,3%), the high prevalence of chronic extra genital diseases.  Thus,
      the results of the given study proves that reproductive disorders develop under
      the influence of a complex of sociomedical factors and lifestyle; They
      predetermine reproductive abnormalities, inadequate reproductive behaviour, the
      low standard of knowledge of contraception.

PMID- 22392780
TI  - [Use of trental for correction of disorders in the system of hemostasys in
      patients with fibro-cavernous tuberculosis and chronic pulmonary heart].
AB  - The effect of trental on hemostasys system depending on the degree of heart
      failure was studied in patients with fibrocavernous pulmonary tuberculosis
      complicated by chronic pulmonary heart disease. Established the desirability of
      placing trental in the treatment regimen of patients with fibrocavernous
      pulmonary tuberculosis and compensated CPHD in order to correct violations of the
      microcirculation and prevention of circulatory decompensation.

PMID- 22392781
TI  - [Clinical trials and intensive therapy of the swine flu (H1N1)].
AB  - During the recent years there's a high index of the swine flu A (H1N1) disease in
      the whole world. In Georgia it began to spread at the end of Autumn 2009. The aim
      of our study was to define clinical trials of the swine flu (H1N1) in patients of
      Republic Clinical Hospital in Batumi from 2009 to 2011 and to generalize the
      methods of treatment. In the hospital there were 94 patients suffering from the
      swine flu (H1N1) disease, 20 of which due to their critical situation of the
      disease were treated in the department of the intensive therapy. We studied case
      histories of 20 patients, who were undergoing treatment in the department of the
      intensive therapy by the generally acknowledged programme of study and monitoring
      due to their hard disease. Among these 20 patients 10 were women and 10 men. 10
      patients died. The programme of intensive treatment consisted of infusive
      transfusive therapy by the negative water balance, antivirus treatment
      (Tamiflu/Relenza), de-escalation antibiotic therapy, mechanic ventilation of
      lungs, aerosol therapy, plus symptom treatment. In 2011 there were fewer cases of
      the swine flu and the death rate compared to the earlier years. In 2011 of 25
      patients only one patient died, but in 2009-2010 of 69 patients 7 patients died),
      which was conditioned by immunity development. The most frequently used regime of
      lung mechanic ventilation was BIPAR. In the first days antibiotic therapy is not
      defining. It is necessary to find more effective method of antivirus treatment.

PMID- 22392782
TI  - [Application of bacterial thermo-and phagelysates for suppression of malignant
      tumor growth in experimental studies: 1. Anticancer efficacy of thermo- and
      phagelysates of E.coli].
AB  - Immunotherapy is considered as one of the promising treatment strategies for
      patients with malignant tumors. In the presented work antitumor effects of E.coli
      thermo- and phagelysates on Ehrlich carcinoma growth in mice have been studied.
      The treatment efficacy was evaluated by estimation of dynamic changes in volume
      of cancer tissue and by the percentage of cancer growth inhibition. Semi
      empirical mathematical model, describing cancer volume variations in relation to
      time, passed after Ehrlich carcinoma inoculation was elaborated. It was shown
      that at the early stage of cancer growth both tested bacterial preparations
      significantly inhibit cancer growth. Antitumor treatment effects were better
      expressed in animal studies using bacterial phagelysates in comparison to that of
      thermolysates. After cessation of administration of bacterial preparations a
      prolonged antitumor activity in animals treated with E. coli phagelysates was
      demonstrated.

PMID- 22392783
TI  - [The aspects of pricing policy in Azerbaijan pharmaceutical sector].
AB  - The effect of macro-, middle- and microeconomic factors on price formation in
      Azerbaijan pharmaceutical market has been studied. Worldwide pharmaceutical
      leaders have the goals to become leader on the pharmaceutical market of
      Azerbaijan and maximize their market share. Non-leaders pharmaceutical companies
      use different strategies of price formation: prime cost plus markup, or price
      formation on the base of current prices.   It was revealed that domestic
      pharmaceutical market has high demand elasticity. Future market development is
      related to stimulation of product development, and hard penetration to the market
      through realization of price formation strategy.  Non-state pharmaceutical
      organizations to achieve the purpose of survive in conditions of high competition
      should take in to account the factor perceptions of assortment by customers.

PMID- 22392784
TI  - [Postsynaptic reactions of cerebral cortex neurons, activated by nociceptive
      afferents during stimulation of the Raphe nuclei].
AB  - On cats, we studied the influence of stimulation of the Raphe nuclei (RN) on
      postsynaptic processes evoked in neurons of the somatosensory cortex by
      stimulation of nociceptive (intensive stimulation of the tooth pulp) and non
      nociceptive (moderate stimulation of the ventroposteromedial--VPN--nucleus of the
      thalamus) afferent inputs. 6 cells, selectively excited by stimulation of
      nocciceptors and 9 cells, activated by both the above nociceptive and non
      nociceptive influences (nociceptive and convergent neurons, respectively) were
      recorded intracellular. In neurons of both groups, responses to nociceptive
      stimulation (of sufficient intensity) looked like an EPSP-spike-IPSP (the letter
      of significant duration, up to 200-300 ms) complex. Conditioning stimulation of
      the RN which preceded test stimulus applied to the tooth pulp or VPM nucleus by
      100 to 800 ms, induced 40-60 % decrease of the IPSP amplitude only, while maximal
      effect of influence, in both cases, was noted within intervals of 300-800 ms
      between conditioning and test stimulus. During stimulation of the RN, serotonin
      released via receptor and second messengers, provides postsynaptic modulation of
      GABAergic system, decreasing the IPSP amplitude which occurs after stimulation of
      both the tooth pulp and VPM thalamic nucleus. This process may be realized trough
      either pre- or postsynaptic mechanisms.

PMID- 22392785
TI  - [Antibiotic resistance of nosocomial strains of Staphylococcus spicies].
AB  - 115 clinical strains of Staphylococcus spicies were isolated in 2005-2010 and
      investigated from patients with wound infections hospitalized in Tbilisi surgical
      clinics. Detection of sensitivity/resistance to several groups of antibiotics,
      was detected by serial dilution method on agar media. During the period of
      testing, was detected increase in 2-fold of meticillin-resistant St. aureus and
      in 3-fold of meticillin-resistant St. epidermidis strains. Important increase of
      resistant Staphylococcus strains was identified to aminoglycosides, macrolides,
      lincosamines, tetracyclines and ftorchuinolons. Investigated strains of
      staphylococci were characterized by 100% sensitivity to vancomycine and
      linezolid.

PMID- 22392786
TI  - [Irradiation doses of population in mountainous Adjara region of Georgia].
AB  - Radionuclide content of food and water in high mountainous regions of Georgia -
      Adjara (Keda, Shuakhevi, Khulo) has been studied, internal and total irradiation
      doses for the population have been defined and preventive measures for its
      reduction have been proposed.   Internal irradiation dose for the population
      caused by K-40 was identified as 0,63 mSv/y, total irradiation dose - 1,73 mSv/y,
      that slightly exceeds acceptable levels, due to this it seems desirable to
      provide some measures with aim to reduce the radiation dose of the population and
      conduct further observation of the radiation situation.  Measures intended to
      reduce irradiation doses includes: provision of population with less radioactive
      water sources, the regulation of medical radiation procedures (mostly - X-ray
      diagnostic procedures), the rational use of fertilizers with 40K content,
      construction of buildings on the territories with the lowest values of gamma
      radiation and radon release from soil, use of materials with low content of
      natural radionuclides for building construction, provision of premises with
      effective ventilation and radiation monitoring of buildings at any stages of
      construction, reconstruction or repair.

PMID- 22392787
TI  - Effects of chronic memantine treatment on hippocampal extracellular glutamate and
      GABA levels during spatial alternation testing.
AB  - These experiments examined the release of glutamate (Glu) and GABA in the
      hippocampus of memantine (2,5mg/kg, i.p. for four weeks) or saline treated rats
      prior to, during, and after spontaneous alternation test. Glu and GABA release
      during the 10 min samples taken at the time of the behavioral testing of
      memantine or saline treated animals were not different from those seen
      immediately before and after testing. Similarly, the alternation scores were not
      significantly different between groups. We found increase in KCl-stimulated
      glutamate and GABA release in the hippocampus of memantine treated rat compared
      to the saline treated rat. This difference in KCl response between memantine
      treated and control rat was statistically significant (p<0,05). Our evaluation of
      memantine reveals that changes in KCl-stimulated Glu and GABA release after
      chronic memantine treatment did not affect working memory in adult rats assessed
      in spontaneous alternation task.

PMID- 22392788
TI  - Clinical and radiographic distribution of structural damage in erosive and
      nonerosive hand osteoarthritis.
AB  - OBJECTIVE: To characterize the clinical and radiographic joint phenotype in
      erosive hand osteoarthritis (EHOA) and non-EHOA. METHODS: A total of 446 patients
      with HOA (233 with EHOA and 213 with non-EHOA) were evaluated. Demographic (sex
      and age at disease onset), clinical (body mass index and distribution of nodes),
      and radiographic features (Kellgren/Lawrence and Kallman's scores obtained from
      radiographs of both hands) from all patients were recorded. RESULTS: Patients
      with EHOA had a significantly earlier disease onset. Clinical and radiographic
      distribution of structural damage in the distal interphalangeal (DIP), proximal
      interphalangeal (PIP), and first carpometacarpal joints was similar in EHOA and
      non-EHOA. EHOA patients showed higher percentages of nodes and more severe
      radiographic scores; the more severe radiographic score of joints with nodes was
      due to both osteophytes and joint space narrowing (JSN). A direct correlation
      between osteophytes and JSN scores was observed. Central erosions (CE) were more
      prevalent in the DIP joints than in the PIP joints. Gull-wing pattern of CE was
      prevalent in the DIP joints, whereas saw-tooth pattern was prevalent in the PIP
      joints. Marginal erosions (ME) were present in 100% of EHOA patients and in 80%
      of non-EHOA patients. An ordinal correlation between the presence of ME and
      osteophyte score was found. CONCLUSION: We found quantitative, but not
      topographic, differences in structural damage between EHOA and non-EHOA.
      Heberden's nodes, severe radiologic scores, and CE were concentrated in the
      second, third, and fifth DIP joints of both hands. ME were also present in the
      majority of non-EHOA patients.

PMID- 22392789
TI  - A history of the International Pediatric Nephrology Association (IPNA).

PMID- 22392791
TI  - Direct observation of activated hydrogen binding to a supported organometallic
      compound at room temperature.

PMID- 22392790
TI  - Effects of cyclic lipodepsipeptide structural modulation on stability,
      antibacterial activity, and human cell toxicity.
AB  - Bacterial infections are becoming increasingly difficult to treat due to the
      development and spread of antibiotic resistance. Therefore, identifying novel
      antibacterial targets and new antibacterial agents capable of treating infections
      by drug-resistant bacteria is of vital importance. The structurally simple yet
      potent fusaricidin or LI-F class of natural products represents a particularly
      attractive source of candidates for the development of new antibacterial agents.
      We synthesized 18 fusaricidin/LI-F analogues and investigated the effects of
      structure modification on their conformation, serum stability, antibacterial
      activity, and toxicity toward human cells. Our findings show that substitution of
      an ester bond in depsipeptides with an amide bond may afford equally potent
      analogues with improved stability and greatly decreased cytotoxicity. The lower
      overall hydrophobicity/amphiphilicity of amide analogues in comparison with their
      parent depsipeptides, as indicated by HPLC retention times, may explain the
      dissociation of antibacterial activity and human cell cytotoxicity. These results
      indicate that amide analogues may have significant advantages over fusaricidin/LI
      F natural products and their depsipeptide analogues as lead structures for the
      development of new antibacterial agents.

PMID- 22392793
TI  - Satisfaction, motivation, and intent to stay among Ugandan physicians: a survey
      from 18 national hospitals.
AB  - OBJECTIVE: Uganda faces a colossal shortages of human resources for health.
      Previous literature has largely focused on those who leave. This paper reports on
      a study of physicians working in 18 public and private facilities in Uganda as
      part of a larger study of more than 641 hospital-based health workers in Uganda.
      We report what could entice physicians to stay longer, satisfaction with current
      positions, and future career intentions. METHODS: This study took place in 18
      Ugandan hospitals. We describe the 49 physicians who participated in 11 focus
      groups and the 63 physicians who completed questionnaires, out of a larger sample
      of 641 health workers overall. FINDINGS: Only 37% of physicians said they were
      satisfied with their jobs, and 46% reported they were at risk of leaving the
      health sector or the country. After compensation, the largest contributors to
      dissatisfaction among physicians were quality of management, availability of
      equipment and supplies (including drugs), quality of facility infrastructure,
      staffing and workload, political influence, community location, and professional
      development. CONCLUSION: Physicians in our study were highly dissatisfied, with
      almost half the sample reporting a risk to leave the sector or the country. The
      established link in literature between physician dissatisfaction and departure
      from the health system suggests national and regional policy makers should
      consider interventions that address the contributors to dissatisfaction
      identified in our study.

PMID- 22392794
TI  - Africa's middle class women bring entrepreneurial opportunities in breast care
      medical tourism to South Africa.
AB  - Africa's distribution of specialized private health services is severely
      disproportionate. Mismatch between South Africa's excess supply and a huge demand
      potential in an under-serviced continent represents an entrepreneurial
      opportunity to attract patients to South Africa for treatment and recuperative
      holidays. However, effective demand for intra-African medical tourism could be
      constrained by sub-Saharan poverty. Results from interviewing 320 patients and
      five staff at the Johannesburg Breast care Centre of Excellence, however, reject
      this proposition, Africa's middle class women being the target market estimated
      to grow annually by one million while breast cancer incidence increases with
      middle-class lifestyles. Uncovering this potential involves an extensive
      marketing strategy.

PMID- 22392795
TI  - Time spent by health managers in two cultures on work pursuits: real time, ideal
      time and activities' importance.
AB  - OBJECTIVES: We compared health managers' judgements of: (1) the time they spent
      on nine major work activities, (2) the time they thought they should allocate and
      (3) the importance they attributed to each pursuit. These and managers' reasons
      for devoting time to activities were examined in an Anglo and a Confucian-Asian
      country. METHOD: A questionnaire survey of Australian (n = 251) and Singaporean
      health managers (n = 340). RESULTS: In both countries, the correlation between
      judgements of time spent on activities/activities' importance (1 and 3) was
      significantly less than the correlation between time spent/time that should be
      spent (1 and 2), which was less than the correlation between time that should be
      spent/activities' importance (2 and 3). Singaporeans said they devoted more time
      to some activities but the importance attached to work pursuits and the reasons
      given for actual time allocation were similar cross-culturally. CONCLUSIONS:
      There was evidence of considerable disparity between managers' actual and
      preferred time allocation and of the globalization of health managers' work
      values. Evidence regarding time use might contribute to a rethink of how
      managers' efficiency and effectiveness are construed.

PMID- 22392796
TI  - The impact of changes in incentives and governance on the motivation of dental
      practitioners.
AB  - Recent changes to the system of remuneration and contracting arrangements with
      Primary Care Trusts (PCTs) has meant that dental practitioners in the UK have
      experienced several types of incentive and governance arrangements. This paper
      uses data from a qualitative study of 20 dental practitioners to examine the
      influence of different systems of incentives and governance on their motivational
      system. Results show that a perceived reduction in autonomy was the least
      acceptable aspect of the health reforms. The study also suggests that conflict
      between self-interested and altruistic motives may occur where medical
      professionals operate as independent contractors in a small business environment.
      Whilst dentists appeared to show altruistic motives towards their patients,
      priorities towards running an autonomous business enterprise meant that PCT
      managerial requirements, for example, to widen access were not welcomed, because
      of their impact on managerial autonomy. Moreover, whilst dentists' professional
      ethos appeared geared towards achieving technically high quality standards of
      work, this produced tensions against a background of cost containment in a fee
      per-item system of remuneration. The paper raises issues such as the person
      system interaction associated with professional and individual autonomy and the
      importance of reciprocity and fair payment.

PMID- 22392797
TI  - Setting health insurance remuneration rates of private providers in Kenya: the
      role of costing, challenges and implications.
AB  - Successful health financing depends on prudent design of resource collection,
      pooling and purchasing. One of the critical purchasing design issues is the
      provider payment mechanism and the remuneration rates, which need to set
      appropriate incentives to health providers. In order to set remuneration rates,
      cost information is required, but this is not known in many developing countries.
      This paper illuminates the role of costing and the challenges of resetting health
      insurance remuneration rates for private hospitals in Kenya and discusses the
      implications and lessons. The results and proceedings of costing studies from
      Kenya are reviewed, which reveals methodological and practical challenges as to
      revising remuneration rates. The costing results are characterized by high
      variability, which is, among other factors, due to suboptimal resource use at
      some hospitals and provider payment mechanisms that incentivise over-provision.
      In such a context, hospital-specific remuneration rates are advisable. In
      conclusion, remuneration rate setting is not just about translating costing
      results into a price tag, but other factors have to be considered in a low-income
      country context in order to balance out health sector objectives and provider
      interests. Inclusion of providers in developing the costing methodology proves
      important to increase acceptability of results.

PMID- 22392800
TI  - AccERK2, a map kinase gene from Apis cerana cerana, plays roles in stress
      responses, developmental processes, and the nervous system.
AB  - Extracellular signal-regulated kinase (ERK), a mitogen-activated protein kinase
      (MAPK), plays roles in a variety of cellular responses. However, limited
      information is available on the relationship between ERKs and environmental
      stresses. In this report, an ERK gene, AccERK2, was cloned and characterized from
      Apis cerana cerana. Polypeptide sequence alignment revealed that the single
      copied AccERK2 shares high identity with other known ERKs and contains the
      typical conserved Thr-Glu-Tyr (TEY) motif in its activation loop. Genomic
      sequence analysis revealed that the seven exons of AccERK2 are interrupted by six
      introns, and the seventh intron is located in the 3' untranslated region. Semi
      quantitative reverse transcription (RT-PCR) indicated that AccERK2 was expressed
      at higher levels in the larval and pupal stages than in the adult stage. AccERK2
      was also most highly expressed in the brain. The expression of AccERK2 was
      induced by abiotic stresses, including heat, ion irradiation, oxidative stress,
      and heavy metal ions. Based on these results, it appears that AccERK2 in A.
      cerana cerana participates in developmental processes, the nervous system, and
      responses to environmental stressors.

PMID- 22392799
TI  - Self-rated health and symptomatic knee osteoarthritis over three years: data from
      a multicenter observational cohort study.
AB  - OBJECTIVE: To determine if a previously published model of the influence of self
      rated health on physical, mental, and social health among patients with joint
      replacement surgery could be generalized to persons with symptomatic knee
      osteoarthritis (OA). Our second purpose was to determine if self-rated health
      mediated changes in physical, mental, and social health. METHODS: Persons with
      symptomatic knee OA (n = 1,127) who participated in the Osteoarthritis Initiative
      study completed the required measures at baseline and at 1-, 2-, and 3-year
      intervals. The key variable of interest was a single-item self-rated health
      measure. In addition, measures of physical, mental, and social health and a set
      of covariate measures over the 3-year period were analyzed. Structural equation
      modeling was used to test interrelationships among variables, as well as
      predictive and mediational relationships among self-rated health and mental,
      physical, and social health after adjusting for baseline covariates. RESULTS: The
      full model demonstrated good statistical fit. Prior self-rated health
      consistently predicted current mental health and social health. Prior social
      health predicted current self-rated health. Self-rated health also mediated
      changes in mental health and social health. Only social health changes were
      mediated by self-rated health over all time periods. CONCLUSION: Self-rated
      health predicts a variety of outcomes of symptomatic knee OA. In addition, self
      rated health mediates changes in social health and mental health. The use of self
      rated health as a simple and efficient clinical assessment has potential for
      clinical utility because of its predictive capability and association with
      multiple health domains.

PMID- 22392801
TI  - Effect of Moringa oleifera flower extract on larval trypsin and
      acetylcholinesterase activities in Aedes aegypti.
AB  - Aedes aegypti control is crucial to reducing dengue fever. Aedes aegypti larvae
      have developed resistance to organophosporous insecticides and the use of natural
      larvicides may help manage larval resistance by increasing elements in
      insecticide rotation programs. Here, we report on larvicidal activity of Moringa
      oleifera flower extract against A. aegypti L(1), L(2), L(3), and L(4) as well as
      the effect of flower extract on gut trypsin and whole-larval acetylcholinesterase
      from L(4.) In addition, the heated flower extract was investigated for larvicidal
      activity against L(4) and effect on larval gut trypsin. Moringa oleifera flower
      extract contains a proteinaceous trypsin inhibitor (M. oleifera flower trypsin
      inhibitor, MoFTI), triterpene (beta-amyrin), sterol (beta-sitosterol) as well as
      flavonoids (kaempferol and quercetin). Larvicidal activity was detected against
      L(2), L(3), and L(4) (LC(50) of 1.72%, 1.67%, and 0.92%, respectively). Flower
      extract inhibited L(4) gut trypsin (MoFTI K(i) = 0.6 nM) and did not affect
      acetylcholinesterase activity. In vivo assay showed that gut trypsin activity
      from L(4) treated with M. oleifera flower extract decreased over time (0-1,440
      min) and was strongly inhibited (98.6%) after 310 min incubation;
      acetylcholinesterase activity was not affected. Thermal treatment resulted in a
      loss of trypsin inhibitor and larvicidal activities, supporting the hypothesis
      that flower extract contains a proteinaceous trypsin inhibitor that may be
      responsible for the deleterious effects on larval mortality.

PMID- 22392802
TI  - A complex of genes involved in adaptation of Leptinotarsa decemlineata larvae to
      induced potato defense.
AB  - The Colorado potato beetle (Leptinotarsa decemlineata) is the most important pest
      of potato in many areas of the world. One of the main reasons for its success
      lies in the ability of its larvae to counteract plant defense compounds. Larvae
      adapt to protease inhibitors (PIs) produced in potato leaves through substitution
      of inhibitor-sensitive digestive cysteine proteases with inhibitor-insensitive
      cysteine proteases. To get a broader insight into the basis of larval adaptation
      to plant defenses, we created a "suppression subtractive hybridisation" library
      using cDNA from the gut of L. decemlineata larvae fed methyl jasmonate-induced or
      uninduced potato leaves. Four hundred clones, randomly selected from the library,
      were screened for their relevance to adaptation with DNA microarray
      hybridizations. Selected enzyme systems of beetle digestion were further
      inspected for changes in gene expression using quantitative PCR and enzyme
      activity measurements. We identified two new groups of digestive cysteine
      proteases, intestains D and intestains E. Intestains D represent a group of
      structurally distinct digestive cysteine proteases, of which the tested members
      are strongly upregulated in response to induced plant defenses. Moreover, we
      found that other digestive enzymes also participate in adaptation, namely,
      cellulases, serine proteases, and an endopolygalacturonase. In addition, juvenile
      hormone binding protein-like (JHBP-like) genes were upregulated. All studied
      genes were expressed specifically in larval guts. In contrast to earlier studies
      that reported experiments based on PI-enriched artificial diets, our results
      increase understanding of insect adaptation under natural conditions.

PMID- 22392803
TI  - Differential expression of the Bombyx mori diapause-termination timer gene Ea4 in
      diapause-inducing temperature and photoperiod.
AB  - Diapause in Bombyx mori eggs is induced by temperature and photoperiod at the
      stage of embryonic development in the maternal generation. In those diapause
      eggs, Esterase-A4 is suggested to serve as a diapause-termination timer (TIME
      EA4), because its ATPase activity shows an interval-timer elevation after acid
      treatment or chilling of eggs to break diapause. To clarify whether the timed
      ATPase activity of TIME-EA4 is related to its gene (Ea4) expression, we analyzed
      Ea4 mRNA of eggs in diapause-inducing environmental conditions. Reverse
      transcription PCR (RT-PCR) analysis showed that the level of Ea4 mRNA was lower
      in 15DD than in 25LL (P < 0.01) or in 20LD (P < 0.01) but did not oscillate when
      photoperiod and temperature periodically oscillated (P > 0.05). Furthermore,
      expressed sequence tag profile and gene microarray analysis demonstrated that Ea4
      showed stage-specific and tissue-specific expression during postembryonic stages,
      high Ea4 mRNA in the spinning and eclosion stages, and in integument and head,
      but low in gonads of fifth-instar day-3 larvae. Then we analyzed the relationship
      between TIME-EA4 ATPase activities and Ea4 gene expression. The ATPase activities
      in diapause eggs laid by the resultant adults transiently elevated after
      treatments to break diapause, that is, at 1.5 h after common-acid treatment and
      day 13 after chilling at 5 degrees C. However, these elevations of enzyme
      activities were not accompanied by any increases in Ea4 mRNA levels. In
      conclusion, the termination of the Bombyx embryonic diapause is related to TIME
      EA4 but not to its gene expression.

PMID- 22392805
TI  - Hepatitis C virus entry: beyond receptors.
AB  - HCV is a blood-borne pathogen that affects approximately 3% of the global
      population and leads to progressive liver disease. Recent advances have
      identified an essential role for host cell molecules: tetraspanin CD81, scavenger
      receptor B1 and the tight junction proteins claudin-1 and occludin in HCV entry,
      suggesting a complex multi-step process. The conserved nature of this receptor
      dependent step in the viral life cycle offers an attractive target for
      therapeutic intervention. Evidence is emerging that additional factors other than
      classical receptors, such as inflammatory mediators regulate the ability of
      hepatocytes to support HCV entry, and as such may provide potential avenues for
      drug design and development. In this review, we summarise the recent literature
      on HCV entry mechanisms with a view to realising the future potential of
      therapeutically targeting this process.

PMID- 22392804
TI  - Pre-surgery disability compensation predicts long-term disability among workers
      with carpal tunnel syndrome.
AB  - BACKGROUND: We sought to identify early risk factors for work disability
      compensation prior to and after carpal tunnel syndrome (CTS) surgery, and to
      determine whether pre-surgery disability compensation is associated with long
      term disability. METHODS: Washington State workers' compensation administrative
      data and data from interviews with workers 18 days (median) after submitting new
      workers' compensation claims for CTS were examined. Baseline risk factors for pre
      surgery disability compensation and for long-term disability (>365 days of work
      disability compensation prior to 2 years after claim filing) were evaluated for
      workers who underwent CTS surgery and had at least 1 day of disability
      compensation (N = 670). RESULTS: After adjustment for baseline long-term
      disability risk factors, workers with pre-surgery disability compensation had
      over five times the odds of long-term disability. Baseline factors in multiple
      domains, including job, psychosocial, clinical, and worker pain and function,
      were associated with both pre-surgery disability compensation and long-term
      disability. CONCLUSIONS: Risk factors for work disability prior to and after CTS
      surgery are similar, and early work disability is a risk factor for long-term CTS
      related disability. An integrated approach to CTS-related disability prevention
      could include identifying and addressing combined risk factors soon after claim
      filing, more efficient use of conservative treatments and appropriate work
      modifications to minimize early work loss, and, when indicated, timely surgical
      intervention.

PMID- 22392806
TI  - Bicyclic oxygen heterocycles from gamma,delta-unsaturated alcohols: synthetic
      targets inspired by blepharocalyxin D.
AB  - trans-2,8-Dioxabicyclodecanes were prepared in high yield with the creation of up
      to three stereocenters in a single pot by the acid-mediated reaction of
      gamma,delta-unsaturated alcohols with aldehydes (see scheme, Bn=benzyl). This
      versatile reaction enables the stereoselective introduction of substituents at
      the C3, C4, C7, and C9 positions of the bicyclic framework.

PMID- 22392807
TI  - Gap opening in the zeroth Landau level in gapped graphene: pseudo-Zeeman
      splitting in an angular magnetic field.
AB  - We present a theoretical study of gap opening in the zeroth Landau level in
      gapped graphene as a result of pseudo-Zeeman interaction. The applied magnetic
      field couples with the valley pseudospin degree of freedom of the charge carriers
      leading to the pseudo-Zeeman interaction. To investigate its role in transport at
      the charge neutrality point (CNP), we study the integer quantum Hall effect in
      gapped graphene in an angular magnetic field in the presence of pseudo-Zeeman
      interaction. Analytical expressions are derived for the Hall conductivity using
      the Kubo-Greenwood formula. We also determine the longitudinal conductivity for
      elastic impurity scattering in the first Born approximation. We show that pseudo
      Zeeman splitting leads to a minimum in the collisional conductivity at high
      magnetic fields and a zero plateau in the Hall conductivity. Evidence for
      activated transport at CNP is found from the temperature dependence of the
      collisional conductivity.

PMID- 22392808
TI  - Fluorescent assay for directed evolution of perhydrolases.
AB  - Directed evolution offers opportunities to improve promiscuous activities of
      hydrolases in rounds of diversity generation and high-throughput screening. In
      this article, we developed and validated a screening platform to improve the
      perhydrolytic activity of proteases and likely other hydrolases (e.g., lipases or
      esterases). Key was the development of a highly sensitive fluorescent assay
      (sensitivity in the uM range) based on 3-carboxy-7-hydroxycoumarin (HCC)
      formation. HCC is released through an hypobromite-mediated oxidation of 7-(4'
      aminophenoxy)-3-carboxycoumarin (APCC), which enables for the first time a
      continuous measurement of peroxycarboxylic acid formation with a standard
      deviation of 11% in microtiter plates with a wide pH range window (5-9). As
      example, subtilisin Carlsberg was subjected to site saturation mutagenesis at
      position G165, yielding a variant T58A/G165L/L216W with 5.4-fold increased k(cat)
      for perhydrolytic activity compared with wild type.

PMID- 22392809
TI  - Perspectives on the discovery of small-molecule modulators for epigenetic
      processes.
AB  - Epigenetic gene regulation is a critical process controlling differentiation and
      development, the malfunction of which may underpin a variety of diseases. In this
      article, we review the current landscape of small-molecule epigenetic modulators
      including drugs on the market, key compounds in clinical trials, and chemical
      probes being used in epigenetic mechanistic studies. Hit identification
      strategies for the discovery of small-molecule epigenetic modulators are
      summarized with respect to writers, erasers, and readers of histone marks.
      Perspectives are provided on opportunities for new hit discovery approaches, some
      of which may define the next generation of therapeutic intervention strategies
      for epigenetic processes.

PMID- 22392810
TI  - Development of biochemical assays for the identification of eIF4E-specific
      inhibitors.
AB  - Control of mRNA translation plays a critical role in cell growth, proliferation,
      and differentiation and is tightly regulated by AKT and RAS oncogenic pathways. A
      key player in the regulation of this process is the mRNA 5' cap-binding protein,
      eukaryotic translation initiation factor 4E (eIF4E). eIF4E contributes to
      malignancy by selectively enabling the translation of a limited pool of mRNAs
      that generally encode key proteins involved in cell cycle progression,
      angiogenesis, and metastasis. Several data indicate that the inhibition of eIF4E
      in tumor cell lines and xenograft models impairs tumor growth and induces
      apoptosis; eIF4E, therefore, can be considered a valuable target for cancer
      therapy. Targeting the cap-binding pocket of eIF4E should represent a way to
      inhibit all the eIF4E cellular functions. We present here the development and
      validation of different biochemical assays based on fluorescence polarization and
      surface plasmon resonance techniques. These assays could support high-throughput
      screening, further refinement, and characterization of eIF4E inhibitors, as well
      as selectivity assessment against CBP80/CBP20, the other major cap-binding
      complex of eukaryotic cells, overall providing a robust roadmap for development
      of eIF4E-specific inhibitors.

PMID- 22392811
TI  - Surface-grafted polymer-assisted electroless deposition of metals for flexible
      and stretchable electronics.
AB  - Surface-grafted polymers, that is, ultrathin layers of polymer coating covalently
      tethered to a surface, can serve as a particularly promising nanoplatform for
      electroless deposition (ELD) of metal thin films and patterned structures. Such
      polymers consist of a large number of well-defined binding sites for highly
      efficient and selective uptake of ELD catalysts. Moreover, the polymer chains
      provide flexible 3D network structures to trap the electrolessly deposited metal
      particles, leading to strong metal-substrate adhesion. In the past decade,
      surface-grafted polymers have been demonstrated as efficient nanoplatforms for
      fabricating durable and high-performance metal coatings by ELD on plastic
      substrates for applications in flexible and stretchable electronics. This focus
      review summarizes these recent advances, with a particular focus on applications
      in polymeric flexible and stretchable substrates. An outlook on the future
      challenges and opportunities in this field is given at the end of this paper.

PMID- 22392812
TI  - Polyhedral AgBr microcrystals with an increased percentage of exposed {111}
      facets as a highly efficient visible-light photocatalyst.
AB  - Synthesis of inorganic single crystals with exposed high-reactivity facets is a
      desirable target in the catalytic chemistry field. Polyhedral AgBr microcrystals
      with an increased percentage of exposed high-reactivity {111} facets have been
      successfully prepared for the first time, and the photocatalytic performance of
      these microcrystals when used as an AgBr/Ag plasmonic photocatalyst was
      investigated. The results indicate that the as-prepared sample has high
      photocatalytic activity and, under the same measurement conditions, the
      photodegradation rate of methyl orange dye over these microcrystals is at least
      four times faster than with other shapes of AgBr/Ag microstructure, as well as 20
      times faster than with the highly efficient Ag(3)PO(4) photocatalyst. DFT
      calculations suggest that the AgBr (111) surface is mainly composed of
      unsaturated Ag atoms and has a relatively high surface energy, both of which are
      favorable for enhancing the photocatalytic activity of the AgBr/Ag polyhedron
      photocatalyst. This work not only provides a highly efficient plasmonic
      photocatalyst of polyhedral AgBr/Ag microcrystals with an increased percentage of
      exposed high-reactivity AgBr {111} facets, but also demonstrates that the shape
      and crystalline quality of the exposed facets have an important influence on the
      photocatalytic activities.

PMID- 22392813
TI  - Disease activity and disability in women and men with early rheumatoid arthritis
      (RA): an 8-year followup of a Swedish early RA project.
AB  - OBJECTIVE: To compare women and men regarding the course of disease activity and
      disability over 8 years from diagnosis of recent-onset rheumatoid arthritis (RA).
      METHODS: A total of 149 patients were followed in the Swedish TIRA study (Early
      Intervention in RA) for 8 years from RA diagnosis (1996-1998) regarding 28-joint
      count Disease Activity Score (DAS28), pain (visual analog scale), grip force,
      Grip Ability Test (GAT), Signals of Functional Impairment (SOFI; hand,
      upper/lower extremity), walking speed, activity limitation (Health Assessment
      Questionnaire [HAQ]), and prescribed disease-modifying antirheumatic drugs
      (DMARDs). RESULTS: Disease activity pattern over time was similar in women and
      men, showing improvement during the first year and a stable situation during 6
      years thereafter. However, at the 7- and 8-year followup times, deterioration was
      seen with a less favorable course in women. HAQ score did not differ between
      sexes at diagnosis, but at all followup times women had significantly higher
      scores than men. Women also had lower grip force and lower walking speed, but
      higher upper extremity mobility. DMARD prescription was similar for both sexes.
      Over 8 years, disease duration, sex, biologic agents, grip force, SOFI hand, and
      pain intensity together explained 43% of the variation in DAS28, whereas grip
      force, SOFI lower extremity, GAT, and pain intensity could together explain 55%
      of variations in HAQ score. CONCLUSION: Disease activity was fairly well managed,
      but disability gradually worsened. Despite similar medication, women had more
      disability than men. The discrepancy between disease activity and disability
      indicates unmet needs for multiprofessional interventions to prevent progressing
      disability, and patients at risk for disability need to be identified early in
      the process.

PMID- 22392814
TI  - In vivo multicolor molecular MR imaging using diamagnetic chemical exchange
      saturation transfer liposomes.
AB  - A variety of (super)paramagnetic contrast agents are available for enhanced MR
      visualization of specific tissues, cells, or molecules. To develop alternative
      contrast agents without the presence of metal ions, liposomes were developed
      containing simple bioorganic and biodegradable compounds that produce diamagnetic
      chemical exchange saturation transfer MR contrast. This diamagnetic chemical
      exchange saturation transfer contrast is frequency-dependent, allowing the unique
      generation of "multicolor" images. The contrast can be turned on and off at will,
      and standard images do not show the presence of these agents. As an example,
      glycogen, L-arginine, and poly-L-lysine were encapsulated inside liposomes and
      injected intradermally into mice to image the lymphatic uptake of these
      liposomes. Using a frequency-dependent acquisition scheme, it is demonstrated
      that multicolor MRI can differentiate between different contrast particles in
      vivo following their homing to draining lymph nodes. Being nonmetallic and
      bioorganic, these diamagnetic chemical exchange saturation transfer liposomes
      form an attractive novel platform for multicolor imaging in vivo.

PMID- 22392815
TI  - Cigarette smoking in building trades workers: the impact of work environment.
AB  - BACKGROUND: Blue-collar workers smoke at higher rates than white-collar workers
      and the general population. Occupational factors may contribute to smoking
      behavior in this group. However, little is known about the role of occupational
      factors in explaining cigarette-smoking patterns. METHODS: This study used cross
      sectional data from the MassBUILT smoking cessation intervention study.
      Multivariable logistic regression analysis was conducted to investigate the
      association of occupational factors with current cigarette smoking among 1,817
      building trades workers. RESULTS: Current cigarette smoking was significantly
      associated with the following occupational factors: union commitment (OR = 1.06;
      95% CI: 1.00-1.12); exposure to dust (OR = 1.50; 95% CI: 1.15-1.95), exposure to
      chemicals (OR = 1.41; 95% CI: 1.11-1.79); and concern about exposure to
      occupational hazards (OR = 0.93; 95% CI: 0.91-0.95). CONCLUSION: The findings
      highlight the need to explicate the pathways by which occupational factors may
      contribute to current smoking behavior among building trades workers. Smoking
      cessation programs for this population should consider work-related occupational
      factors along with individual approaches.

PMID- 22392816
TI  - Computer-controlled, MR-compatible foot-pedal device to study dynamics of the
      muscle tendon complex under isometric, concentric, and eccentric contractions.
AB  - PURPOSE: To design a computer-controlled, magnetic resonance (MR)-compatible foot
      pedal device that allows in vivo mapping of changes in morphology and in strain
      of different musculoskeletal components of the lower leg under passive,
      isometric, concentric, and eccentric contractions. MATERIALS AND METHODS: A
      programmable servomotor in the control room pumped hydraulic fluid to rotate a
      foot-pedal inside the magnet. To validate the performance of the device, six
      subjects were imaged with gated velocity-encoded phase-contrast (VE-PC) imaging
      to investigate the dynamics of muscle and aponeurotic structures. RESULTS:
      Artifact-free VE-PC imaging clearly delineated different muscle compartments by
      differences in distribution of mechanical strains. High repeatability of
      contraction cycles allowed establishing that fascicles lengthened 6.1% more
      during passive compared with eccentric contractions. Aponeurosis separation
      during passive (range between three locations: -2.6~1.3 mm) and active (range: 
      2.4~1.6 mm) contractions were similar but significantly different from concentric
      (range: -0.9~3.3 mm), with proximal and distal regions showing mostly negative
      values for the first two modes, but positive for the last. CONCLUSION: The device
      was sufficiently robust and artifact-free to accurately assess, using VE-PC
      imaging, physiologically important structure and dynamics of the musculotendon
      complex.

PMID- 22392818
TI  - A pure silica chiral polymorph with helical pores.
AB  - A microporous polymorph of SiO(2), HPM-1, has a chiral structure and contains
      helical pores. The defect-free pure SiO(2) composition, which has been previously
      considered unfeasible for this structure type, bestows a high thermal and
      hydrothermal stability upon this material.

PMID- 22392817
TI  - Inflammatory markers and the risk of hip fracture: the Women's Health Initiative.
AB  - Cytokines play a major role in bone remodeling in vitro and in animal models,
      with evidence supporting the involvement of inflammatory markers in the
      pathogenesis of osteoporosis. However, less is known about the longitudinal
      association of inflammatory markers with hip fracture. We tested whether high
      receptor levels of proinflammatory cytokines are associated with an increased
      risk of hip fracture in older women. We used a nested case-control study design
      from the Women's Health Initiative Observational Study (WHI-OS) and selected 400
      cases with physician-adjudicated incident hip fractures and 400 controls matched
      on age, race, and date of blood draw. Participants were chosen from 39,795
      postmenopausal women without previous hip fractures, not using estrogens or other
      bone-active therapies. Incident hip fractures (median follow-up 7.1 years) were
      verified by review of radiographs and confirmed by blinded central adjudicators.
      Hip fractures with a pathological cause were excluded. In multivariable models,
      the risk of hip fracture for subjects with the highest levels of inflammatory
      markers (quartile 4) compared with those with lower levels (quartiles 1, 2, and
      3) was 1.43 (95% confidence interval [CI], 0.98-2.07) for interleukin-6 (IL-6)
      soluble receptor (SR), 1.40 (95% CI, 0.97-2.03) for tumor necrosis factor (TNF)
      SR1, and 1.56 (95% CI, 1.09-2.22) for TNF SR2. In subjects with all three markers
      in the highest quartile, the risk ratio of fracture was 2.76 (95% CI, 1.22-6.25)
      in comparison with subjects with 0 or 1 elevated marker(s) (p trend = 0.018).
      Elevated levels of inflammatory markers for all three cytokine-soluble receptors
      were associated with an increased risk of hip fractures in older women. Future
      clinical trials should test whether interventions to decrease inflammatory marker
      levels reduces hip fractures.

PMID- 22392819
TI  - The effects of the magnetopolaron on the energy gap opening in graphene.
AB  - The magnetopolaron is formed via electron-acoustic deformation phonon coupling in
      the presence of a magnetic field in monolayer graphene. We find that an energy
      gap (EG) is opened due to the electron-phonon coupling. Both linear and square
      root forms for the dependence of the EG on the magnetic field are obtained, which
      are in agreement with experimental measurements. Furthermore, we suggest that the
      EG can be estimated through observing the variation of Fermi velocity in
      cyclotron resonance experiments. The relation of the EG with the Debye cut-off
      wavenumber is also discussed.

PMID- 22392820
TI  - Self-assembled hexanuclear organometallic cages: synthesis, characterization, and
      host-guest properties.
AB  - A series of iridium- and rhodium-based hexanuclear organometallic cages
      containing 2,5-dichloro-3,6-dihydroxy-1,4-benzoquinone, 9,10-dihydroxy-1,4
      anthraquinone, and 6,11-dihydroxynaphthacene-5,12-dione ligands were synthesized
      from the self-assembly of the corresponding molecular "clips" and 2,4,6-tri(4
      pyridyl)-1,3,5-triazine ligands in good yields. These organometallic cages can
      form inclusion systems with a wide variety of pi-donor substrates, including
      coronene, pyrene, [Pt(acac)(2)], and hexamethoxytriphenylene. The 1:1
      complexation of the resulting supramolecular assemblies was confirmed by (1)H NMR
      spectroscopy. Large complexation shifts (Deltadelta>1 ppm) were observed in the
      (1)H NMR spectra of guests in the presence of cage [Cp*(6)M(6)(MU
      DHNA)(3)(tpt)(2)](OTf)(6) (6a; M=Ir, tpt=2,4,6-tri(4-pyridyl)-1,3,5-triazine).
      The formation of discrete 1:1 donor-acceptor complexes, pyrene?6b (M=Rh),
      coronene?6a, coronene?6b, and [Pt(acac)(2)]?6a was confirmed by their single
      crystal X-ray analyses. In these systems, the most important driving force for
      the formation of guest-host complexes is clearly the donor-acceptor pi...pi
      stacking interaction, including charge-transfer interactions between the electron
      donating and electron-accepting aromatic components. These structures provide
      compelling evidence for the existence of strong attractive forces between the
      electron-deficient triazine core and electron-rich guest. The results presented
      here may provide useful guidance for designing artificial receptors for
      functional biomolecules.

PMID- 22392821
TI  - Paper-based electrochemiluminescent 3D immunodevice for lab-on-paper, specific,
      and sensitive point-of-care testing.
AB  - Recent research on microfluidic paper-based analytical devices (MUPADs) has shown
      that paper has great potential for the fabrication of low-cost diagnostic devices
      for healthcare and environmental monitoring applications. Herein,
      electrochemiluminescence (ECL) was introduced for the first time into MUPADs that
      were based on screen-printed paper-electrodes. To further perform high
      specificity, high-performance, and high-sensitivity ECL on MUPADs for point-of
      care testing (POCT), ECL immunoassay capabilities were introduced into a wax
      patterned 3D paper-based ECL device, which was characterized by SEM, contact
      angle measurement, and electrochemical impedance spectroscopy. With the aid of a
      home-made device-holder, the ECL reaction was triggered at room temperature. By
      using a typical tris(bipyridine)ruthenium-tri-n-propylamine ECL system, this
      paper-based ECL 3D immunodevice was applied to the diagnosis of carcinoembryonic
      antigens in real clinical serum samples. This contribution further expands the
      number of sensitive and specific detection modes of MUPADs.

PMID- 22392822
TI  - Small-tip-angle spokes pulse design using interleaved greedy and local
      optimization methods.
AB  - Current spokes pulse design methods can be grouped into methods based either on
      sparse approximation or on iterative local (gradient descent-based) optimization
      of the transverse-plane spatial frequency locations visited by the spokes. These
      two classes of methods have complementary strengths and weaknesses: sparse
      approximation-based methods perform an efficient search over a large swath of
      candidate spatial frequency locations but most are incompatible with off
      resonance compensation, multifrequency designs, and target phase relaxation,
      while local methods can accommodate off-resonance and target phase relaxation but
      are sensitive to initialization and suboptimal local cost function minima. This
      article introduces a method that interleaves local iterations, which optimize the
      radiofrequency pulses, target phase patterns, and spatial frequency locations,
      with a greedy method to choose new locations. Simulations and experiments at 3
      and 7 T show that the method consistently produces single- and multifrequency
      spokes pulses with lower flip angle inhomogeneity compared to current methods.

PMID- 22392823
TI  - Comparison of prescription drug costs in the United States and the United
      Kingdom, Part 1: statins.
AB  - STUDY OBJECTIVE: To compare the annual cost of statins in the United States and
      in the United Kingdom. DESIGN: Matched-cohort cost analysis. DATA SOURCES: U.K.
      General Practice Research Database (GPRD), and MarketScan Commercial Claims and
      Encounters Database, a large, U.S. self-insured medical claims database. STUDY
      POPULATION: We initially identified 1.6 million people in the GPRD who were
      younger than 65 years of age in 2005. These people were then matched by year of
      birth and sex with 1.6 million people in the U.S. database. From this matched
      pool, we estimated that 280,000 people aged 55-64 years from each country in 2005
      were prescribed at least one drug. Of these, 91,474 (33%) in the U.S. were
      prescribed a statin compared with 68,217 (24%) in the U.K. After excluding those
      who did not receive statins continuously or who switched statins during the year,
      there remained 61,470 in the U.S. and 45,788 in the U.K. who were prescribed a
      single statin preparation continuously during 2005 (annual statin users). We
      estimated and compared drug costs (presented in 2005 U.S. dollars) separately in
      the two countries. MEASUREMENTS AND MAIN RESULTS: Estimated drug costs were
      determined by random sampling. Estimated annual costs/patient in the U.S. ranged
      from $313 for generic lovastatin to $1428 for nongeneric simvastatin. In the
      U.K., annual costs/patient ranged from $164 for generic simvastatin to $509 for
      nongeneric atorvastatin. The total annual cost of the continuous receipt of
      statins in the U.S. was $64.9 million compared with $15.7 million in the U.K. In
      June 2006, after our study results were analyzed, the U.S. Food and Drug
      Administration approved generic simvastatin. We thus derived cost estimates for
      simvastatin use during 2006 and found that more than 60% of simvastatin users
      switched to the generic product, which reduced the cost/pill by more than 50%.
      CONCLUSION: The cost paid for statins in the U.S. for people younger than 65
      years, who were insured by private companies, was approximately 400% higher than
      comparable costs paid by the government in the U.K. Available generic statins
      were substantially less expensive than those that were still under patent in both
      countries.

PMID- 22392824
TI  - Colony-stimulating factor use and impact on febrile neutropenia among patients
      with newly diagnosed breast, colorectal, or non-small cell lung cancer who were
      receiving chemotherapy.
AB  - STUDY OBJECTIVE: To determine the impact of primary prophylactic colony
      stimulating factor (CSF) use on febrile neutropenia in a large patient population
      receiving contemporary chemotherapy regimens to treat breast cancer, colorectal
      cancer, or non-small cell lung cancer (NSCLC). DESIGN: Retrospective claims
      analysis. DATA SOURCES: The Surveillance, Epidemiology, and End Results (SEER)
      Puget Sound cancer registry and insurance claims records. PATIENTS: A total of
      2728 patients aged 25 years or older who received a diagnosis of breast cancer
      (998 patients), colorectal cancer (688 patients), or NSCLC (1042 patients)
      between January 1, 2002, and December 31, 2005, and received chemotherapy.
      MEASUREMENTS AND MAIN RESULTS: Initial chemotherapy regimen, CSF use (filgrastim
      or pegfilgrastim), and febrile neutropenia events were evaluated after the first
      chemotherapy administration. Subsequently, febrile neutropenia rates in patients
      receiving primary prophylactic CSF were compared with febrile neutropenia rates
      in patients receiving CSF in settings other than primary prophylaxis or not at
      all. The impact of primary prophylactic CSF could not be assessed for patients
      with colorectal cancer or NSCLC because only 1 and 18 febrile neutropenia events,
      respectively, occurred in those receiving primary prophylactic CSF. Of the 998
      patients with breast cancer, 72 (7.2%) experienced febrile neutropenia, 28 of
      whom received primary prophylactic CSF. In the patients with breast cancer, we
      observed that primary prophylactic CSF use was associated with reduced febrile
      neutropenia rates; however, the analysis may have been confounded by unmeasured
      factors associated with febrile neutropenia. CONCLUSION: The impact of primary
      prophylactic CSFs on febrile neutropenia rates could not be demonstrated. Given
      the substantive cost of CSFs to pharmacy budgets, there are numerous
      opportunities for pharmacists to optimize CSF use. Research studies are needed to
      evaluate if guideline-directed prescribing of primary prophylactic CSFs can
      improve clinical outcomes.

PMID- 22392826
TI  - Hansen's disease (Leprosy): current and future pharmacotherapy and treatment of
      disease-related immunologic reactions.
AB  - Hansen's disease, also known as leprosy, remains an important public health
      problem throughout the world, including North America. The causative microbe in
      Hansen's disease is Mycobacterium leprae, an acid-fast organism that is difficult
      to grow in vitro. The nine-banded armadillo is the major animal reservoir in the
      United States. Manifestations of disease vary based on host immune response and
      can range from tuberculoid to lepromatous leprosy (paucibacillary to
      multibacillary disease). Hansen's disease typically affects the skin, nerves, and
      eyes, and patients may present with skin lesions, weakness, numbness, eye pain,
      or loss of vision. Definitive diagnosis is based on a combination of physical
      examination findings and skin biopsy and/or smear. Modern antibacterial therapy
      typically consists of combinations of dapsone and rifampin with or without
      clofazimine. Clofazimine is available only as an investigational drug through the
      National Hansen's Disease Program. Other options include moxifloxacin, ofloxacin,
      minocycline, and clarithromycin. Hansen's disease is associated with type 1
      (reversal) and type 2 (erythema nodosum leprosum) immunologic reactions, during
      which the disease process appears to worsen dramatically. These reactions may
      occur at any time before, during, or after treatment. Antibacterial therapy
      should usually be continued during these reactions. Treatment options for these
      reactions differ based on clinical manifestations and include corticosteroids,
      thalidomide, pentoxiphylline, tumor necrosis factor inhibitors, and T cell
      inhibitors. Prompt diagnosis, antimicrobial therapy, and treatment of reactions
      dramatically reduce complications of the disease.

PMID- 22392825
TI  - Comparison of bivalirudin dosing strategies using total, adjusted, and ideal body
      weights in obese patients with heparin-induced thrombocytopenia.
AB  - STUDY OBJECTIVES: To compare dosing strategies using total body weight (actual
      measured body weight), adjusted body weight, and ideal body weight when starting
      bivalirudin for the treatment for heparin-induced thrombocytopenia (HIT) in obese
      patients, and to compare differences in dosing requirements and clinical outcomes
      between obese and nonobese patients. DESIGN: Retrospective medical record review.
      SETTING: Academic tertiary care medical center. PATIENTS: One hundred thirty-five
      medical and surgical patients who were treated with bivalirudin for HIT between
      June 1, 2004, and October 1, 2009. MEASUREMENTS AND MAIN RESULTS: The 135
      patients were separated into two groups based on body mass index (BMI): 46
      patients had a BMI greater than 30 kg/m(2)  and were classified in the obese
      group; the nonobese group consisted of 89 patients with a BMI less than 30
      kg/m(2) . The mean BMI in the obese group was 37.7 kg/m(2)  (range: 30.1-56.2
      kg/m(2) ). Weight-standardized doses that achieved activated partial
      thromboplastin time (aPTT) goal were compared in the obese group. The mean +/- SD
      doses that achieved aPTT goal with total (actual), adjusted, and ideal body
      weights in this group were 0.1 +/- 0.07, 0.11 +/- 0.08, and 0.14 +/- 0.09
      mg/kg/hour, respectively. Of the three weight-based dosing approaches, total body
      weight followed by adjusted body weight provided the closest correlation to rates
      observed at the target aPTT goal. The secondary analysis compared initial doses
      of bivalirudin, doses required to reach goal aPTT, time to achieve goal aPTT, and
      clinical outcomes (number of patients not achieving goal, new thrombosis, major
      bleeding, and 30-day all-cause mortality) between the obese and nonobese groups.
      A significant difference in initial dose was noted between groups; however, no
      significant differences in dose required to achieve goal aPTT, time to achieve
      goal aPTT, and clinical outcomes were noted between the obese and nonobese
      groups. CONCLUSION: This study provides evidence that the dosing strategy for
      bivalirudin based on total body weight is the most accurate predictor of
      achieving aPTT goal in obese patients with HIT. The study also suggests that
      there are no clinical differences that warrant different dosing strategies
      between obese and nonobese patients. Further prospective studies are needed to
      confirm these findings.

PMID- 22392827
TI  - Testosterone supplementation for hypoactive sexual desire disorder in women.
AB  - Over 50% of women are believed to be affected by female sexual dysfunction (FSD).
      When particularly distressful, FSD is known as hypoactive sexual desire disorder
      (HSDD). In contrast to male sexual dysfunction that has been extensively
      researched, there is less evidence addressing the treatment of HSDD in women,
      particularly with regard to the use of androgen therapy. A variety of
      testosterone products, including oral, injectable, and transdermal preparations,
      has been prescribed for the treatment of HSDD in premenopausal women, as well as
      in those with naturally occurring or surgically induced menopause. Although
      studies have shown some benefit with testosterone supplementation in women with
      HSDD, conflicting evidence and debate regarding the clinical efficacy of
      testosterone remain. Because of concern over potential adverse events, additional
      studies with longer follow-up periods are necessary before use of testosterone in
      women with HSDD becomes widespread. Initiation of testosterone therapy must be
      considered on an individual basis after a thorough discussion with the patient
      about risks and benefits.

PMID- 22392828
TI  - Medical management of adult transsexual persons.
AB  - Gender identity disorder (GID), or transsexualism, is an increasingly recognized
      medical condition with an expanding body of medical literature to support the use
      of established therapeutic guidelines. Transsexualism can be effectively managed
      through exogenous cross-sex hormone administration used to induce development of
      desired sex characteristics, as well as use of other agents, such as aldosterone
      antagonists, aimed at decreasing physical characteristics of the undesired sex.
      Many complications can arise with the use of the available therapies, and these
      must be considered before determining the appropriate course of action. This
      review describes methods, including both pharmacotherapy and surgical
      interventions, for effective medical management of both male and female adults
      with GID. In addition, specific goals of therapy as well as safety aspects with
      long-term use of pharmacotherapeutic agents are discussed. This review also
      discusses some special considerations for treating patients with significant, yet
      common, comorbid diseases such as human immunodeficiency virus infection,
      acquired immunodeficiency syndrome, and viral hepatitis, as these conditions may
      complicate the clinical course and preclude some patients from using certain
      therapies. Pharmacist involvement in the management of transsexualism can be
      extremely beneficial to patients and other health care providers. Pharmacists can
      help determine the appropriate therapy, optimize dosages, monitor for adverse
      effects, and educate patients on what to expect during their therapy. Pharmacists
      should become knowledgeable about guidelines and current literature on
      transsexualism, understand the monitoring parameters for safe and effective
      therapy, and establish themselves as partners in the collaborative management of
      this disorder.

PMID- 22392829
TI  - Fracture risk and bone mineral density reduction associated with proton pump
      inhibitors.
AB  - Many patients receive prolonged proton pump inhibitor (PPI) therapy for upper
      gastrointestinal disorders, but the long-term safety of PPIs, particularly
      increased risk of hip and nonhip fractures, has been questioned. To summarize the
      current literature on the risk of bone mineral density (BMD) reduction and
      fracture associated with PPI therapy, we conducted a literature search to
      identify all pertinent studies from 1980-February 2011. A total of 14
      observational studies were included in this review. Most studies evaluated the
      risk of fracture associated with prolonged PPI exposure. Eight studies found an
      increased fracture risk at the hip, and five studies found an increased fracture
      risk at the spine associated with PPIs. Three studies showed reduction in
      fracture risk associated with PPIs after discontinuation for 1 month-1 year.
      Three studies evaluated the risk of BMD reduction associated with PPIs but did
      not find consistent changes in baseline or subsequent BMD. The current data
      suggest a modest increase in the risk of hip fracture and vertebral fracture
      associated with PPIs, although some studies showed conflicting results. Further
      studies will be needed to determine whether the increased risk of fracture is due
      to PPI exposure or residual confounding.

PMID- 22392830
TI  - Dapagliflozin: a novel sodium-glucose cotransporter type 2 inhibitor for the
      treatment of type 2 diabetes mellitus.
AB  - The prevalence of diabetes mellitus has grown to staggering numbers, and its
      incidence is expected to rise in the next 2 decades. The need for novel
      approaches to treat hyperglycemia cannot be ignored. Current agents have been
      shown to modestly improve glycemia and in some cases prevent complications of
      diabetes, but they become less effective over time and are often accompanied by
      undesirable adverse effects. Dapagliflozin is the lead agent in a new class of
      oral antidiabetic agents known as sodium-glucose cotransporter type 2 (SGLT2)
      inhibitors, which represent a novel approach to the management of type 2 diabetes
      mellitus. By selectively and reversibly blocking the SGLT2 receptor,
      dapagliflozin prevents the reabsorption of glucose at the renal proximal tubule.
      Phase II and III clinical trials have demonstrated that dapagliflozin is a safe
      and effective method for treating type 2 diabetes. Dapagliflozin produces a
      sustained, dose-dependent reduction in plasma glucose levels while simultaneously
      improving insulin secretion and sensitivity. Over 12-24 weeks, reductions in
      hemoglobin A(1c)  ranged from 0.54-0.89% when dapagliflozin was administered
      once/day (either as monotherapy or add-on therapy to oral antidiabetic drugs with
      or without insulin) to patients with type 2 diabetes. Therapy with dapagliflozin
      also results in a mild osmotic-diuretic effect that may account for decreases in
      total body weight (~2-3 kg) and blood pressure (systolic 2-5 mm Hg, diastolic 1.5
      3 mm Hg), and increases in hematocrit (1-2%). Dapagliflozin has a favorable
      safety profile, with the rates of hypoglycemia similar to those of placebo.
      Genital and urinary tract infections were more commonly reported in patients
      taking dapagliflozin (2-13%) than those taking placebo (0-8%). Dapagliflozin does
      not appear to cause electrolyte disturbances, hepatotoxicity, or nephrotoxicity.
      Results from clinical trials have been promising, and well-designed clinical
      programs that address the long-term safety and efficacy of dapagliflozin are
      under way.

PMID- 22392831
TI  - Impaired maraviroc and raltegravir clearance in a human immunodeficiency virus
      infected patient with end-stage liver disease and renal impairment: a management
      dilemma.
AB  - Current product labels for maraviroc and raltegravir provide no dosing guidance
      for patients with end-stage liver disease and worsening renal function. We
      describe a 41-year-old man with human immunodeficiency virus (HIV) infection and
      rapidly progressive liver failure and vanishing bile duct syndrome at
      presentation. Despite discontinuation of all potential offending drugs, the
      patient's liver function continued to deteriorate. To achieve and maintain HIV
      suppression while awaiting liver transplantation, a regimen consisting of
      maraviroc, raltegravir, and enfuvirtide was started. These agents were chosen
      because the patient was not exposed to them before the onset of liver failure.
      While receiving product label-recommended twice-daily dosing of these drugs, he
      achieved and maintained HIV suppression. During a complicated and prolonged
      hospitalization, the patient also developed renal dysfunction. As hepatic
      metabolism is the primary route of clearance of maraviroc and raltegravir, we
      predicted that using approved doses of these drugs could result in significant
      drug accumulation. Since the safety profiles of supratherapeutic concentrations
      of these agents are not well defined, we chose to use therapeutic drug monitoring
      to guide further dosing. The reported concentrations showed severely impaired
      metabolic clearance of both drugs, with markedly prolonged elimination half-lives
      of 189 hours for maraviroc and 61 hours for raltegravir. Previously reported half
      lives for maraviroc and raltegravir in HIV-infected patients with normal hepatic
      and renal function are 14-18 hours and 9-12 hours, respectively. Based on these
      results, the dosing intervals were extended from twice/day to twice/week for
      maraviroc and every 48 hours for raltegravir. Unfortunately, the patient's
      clinical condition continued to deteriorate, and he eventually died of
      complications related to end-stage liver disease. This case illustrates the
      difficulties in managing antiretroviral therapy in an HIV-infected patient with
      combined severe liver and renal failure. Prolonged excessively high exposure to
      maraviroc and raltegravir is likely to result in some level of concentration
      dependent toxicity. Until more data are available, therapeutic drug monitoring
      remains the only evidence-based approach to optimize dosage selection of these
      drugs in this patient population.

PMID- 22392832
TI  - Fanconi's syndrome and nephrogenic diabetes insipidus in an adult treated with
      ifosfamide.
AB  - Fanconi's syndrome is a serious condition characterized by type II proximal renal
      tubular dysfunction, with urinary loss of glucose, amino acids, phosphate,
      bicarbonate, and potassium. Ifosfamide-induced Fanconi's syndrome is reported in
      about 1.4-5% of children being treated for solid tumors, yet only a few cases
      have been reported in adults. We describe a 54-year-old man who came to the
      hospital with symptoms of neutropenic fever 4 days after his fourth cycle of
      ifosfamide and doxorubicin treatment for recurrent sarcoma with metastases to the
      lung. During admission, he was noted to have severe renal tubular dysfunction;
      ifosfamide-induced nephrogenic diabetes insipidus and Fanconi's syndrome were
      suspected. He received supportive therapy that resulted in incomplete resolution
      of signs and symptoms. The patient was discharged after a 5-day hospital stay
      when his white blood cell count increased from 0.1-2.5 * 10(3) /mm(3)  and his
      fever had resolved. Use of the Naranjo adverse drug reaction probability scale
      indicated a probable relationship (score of 7) between the patient's development
      of diabetes insipidus and Fanconi's syndrome and his use of ifosfamide. This dual
      diagnosis of diabetes insipidus and Fanconi's syndrome in an adult makes this
      case unusual, as well as therapeutically challenging. We conducted a review of
      the existing literature regarding ifosfamide-induced Fanconi's syndrome and
      describe the proposed mechanisms and therapeutic options. This case suggests that
      patients treated with ifosfamide should be monitored closely for renal function
      to identify, and perhaps prevent, these rare adverse events. Preliminary animal
      models show promise for adding N-acetylcysteine to ifosfamide treatment, but more
      research is necessary before using this drug as a therapeutic option.

PMID- 22392833
TI  - Liraglutide-induced acute kidney injury.
AB  - Published case reports have documented the relationship between exenatide use and
      acute kidney injury. However, to our knowledge, no cases of this adverse effect
      with liraglutide, another glucagon-like peptide-1 receptor agonist approved for
      the treatment of type 2 diabetes mellitus, have been reported. We describe a 53
      year-old Caucasian woman who came to a community hospital with severe and
      progressively worsening gastrointestinal symptoms for several weeks, leading to
      dehydration and development of acute kidney injury. Laboratory results showed an
      increase in her serum creatinine concentration to 22.8 mg/dl and blood urea
      nitrogen to 150 mg/dl; she also had lost 8.9 kg in the previous month. One month
      earlier, the patient had begun liraglutide 1.8 mg/day subcutaneously for
      uncontrolled type 2 diabetes. Use of the Naranjo adverse drug reaction
      probability scale indicated a possible relationship (score of 3) between the
      patient's development of acute kidney injury and liraglutide. Renal biopsy and
      laboratory testing were helpful in ruling out other potential causes of renal
      failure and adverse drug reactions due to other drugs such as ciprofloxacin and
      quinapril. After the reports of the renal biopsy were obtained, liraglutide was
      determined to be a likely cause of acute tubular necrosis. The patient was
      successfully treated with discontinuation of liraglutide, volume repletion, and
      hemodialysis. To our knowledge, this is the first documented case of liraglutide
      induced acute tubular necrosis. Clinicians should be aware of this possible
      complication and closely follow liraglutide's dosage titration recommendations in
      the package insert. Patients should also be educated about the need to report
      unusual or prolonged gastrointestinal symptoms.

PMID- 22392835
TI  - Quantitative evaluation of liver cirrhosis using T1 relaxation time with 3 tesla
      MRI before and after oxygen inhalation.
AB  - PURPOSE: To quantify liver T1 relaxation times before and after oxygen inhalation
      in patients with and without liver cirrhosis using a 3 Tesla (T) MRI. MATERIALS
      AND METHODS: Institutional Review Board approval and written informed consent
      were obtained. Ninety-two noncirrhotic patients and 87 patients with hepatitis B
      viral liver cirrhosis (72 Child-Pugh class A and 15 Child-Pugh class B or C)
      underwent MRI with a 3.0T system before and after the supply of 100% oxygen at a
      rate of 15 L/min by means of a nonrebreather ventilation mask for 3 min. T1 maps
      were acquired using three-dimensional spoiled gradient echo sequences with two
      different flip angles (2 degrees  and 14 degrees ) and a fixed TR/TE (2.54
      ms/0.95 ms). Liver T1 values were obtained using a T1 processing tool (MapIT
      software). The mean baseline T1 values of three groups (control, Child-Pugh class
      A, and Child-Pugh class B/C) were compared using an analysis of variance test.
      Liver T1 value before and after oxygenation was compared using a paired t-test
      for each group. RESULTS: The baseline liver T1 value was significantly higher in
      the control group (941 +/- 136 ms) than in Child-Pugh A (858 +/- 143 ms) and
      Child-Pugh B/C (783 +/- 164 ms) group (P < 0.001 and P < 0.0001). The reduction
      in the liver T1 value after oxygen inhalation was significant in the control
      group (P = 0.012) but not significant in Child-Pugh class A (P = 0.079) and Child
      Pugh class B/C (P = 0.752). CONCLUSION: The baseline liver T1 relaxation time was
      significantly different between the patients with and without liver cirrhosis.
      The shortening effect of oxygen on the liver T1 value was significant in the
      control group but not in the cirrhotic patients.

PMID- 22392834
TI  - Weight loss in obese older adults increases serum sclerostin and impairs hip
      geometry but both are prevented by exercise training.
AB  - We reported that weight loss induces bone loss which is prevented by exercise
      training; however, the mechanism for this observation remains unclear.
      Sclerostin, an inhibitor of bone formation, has been found to increase in states
      of unloading and may mediate the changes in bone metabolism associated with
      weight loss and exercise. The objective of the study was to determine the effect
      of lifestyle intervention in obese older adults on sclerostin levels, and on hip
      geometry parameters. A total of 107 obese (body mass index [BMI] >= 30 kg/m(2))
      older (>=65 years) adults were randomly assigned to control, diet, exercise, and
      combined diet-exercise for 1 year. Sclerostin levels were measured by ELISA at
      baseline, 6 months, and 12 months, while hip geometry parameters were obtained
      from bone mineral density (BMD) images done by dual-energy X-ray absorptiometry
      using hip structure analysis at baseline and 12 months. Both the diet and diet
      exercise groups had significant decreases in body weight (-9.6% and -9.4%,
      respectively), whereas weight was stable in the exercise and control groups.
      Sclerostin levels increased significantly and progressively in the diet group
      (6.6% +/- 1.7% and 10.5% +/- 1.9% at 6 and 12 months, respectively, all p <
      0.05), whereas they were unchanged in the other groups; in particular, they were
      stable in the diet-exercise group (0.7% +/- 1.6% and 0.4% +/- 1.7% at 6 and 12
      months, respectively, all p = 0.05). Hip geometry parameters showed significant
      decreases in cross-sectional area, cortical thickness, and BMD; and increases in
      buckling ratio at the narrow neck, intertrochanter, and femoral shaft. These
      negative changes on bone geometry were not observed in the diet-exercise group.
      Significant correlations between changes in sclerostin and changes in certain hip
      geometry parameters were also observed (p < 0.05). In conclusion, the increase in
      sclerostin levels with weight loss that was prevented by exercise may partly
      mediate the negative effects of weight loss on bone metabolism and the
      osteoprotective effect of exercise training.

PMID- 22392836
TI  - Hole subbands in freestanding nanowires: six-band versus eight-band k.p
      modelling.
AB  - The electronic structure of GaAs, InAs and InSb nanowires is studied using the
      six-band and the eight-band k.p models. The effect of the different Luttinger
      like parameters (in the eight-band model) on the hole band structure is
      investigated. Although GaAs nanostructures are often treated within a six-band
      model because of the large bandgap, it is shown that an eight-band model is
      necessary for a correct description of its hole spectrum. The camel-back
      structure usually found in the six-band model is not always present in the eight
      band model. This camel-back structure depends on the interaction between light
      and heavy holes, especially the ones with opposite spin. The latter effect is
      less pronounced in an eight-band model, but could be very sensitive to the Kane
      inter-band energy (E(P)) value.

PMID- 22392837
TI  - Hybrid CuO-TiO(2-x)N(x) hollow nanocubes for photocatalytic conversion of CO2
      into methane under solar irradiation.
AB  - Methane-producing hollow nanocubes: Hybrid CuO-TiO(2-x)N(x) hollow nanocubes have
      been synthesized by first depositing TiO(2) onto Cu(3)N nanocube templates, then
      heating in air to oxidize the Cu(3)N to CuO while concomitantly incorporating
      nitrogen into the TiO(2). The nanostructured CuO-TiO(2-x)N(x) material
      photocatalytically converts CO(2) into methane under solar irradiation.

PMID- 22392839
TI  - Diurnal and seasonal variations of surface albedo in a spring wheat field of arid
      lands of Northwestern China.
AB  - Surface albedo greatly affects the radiation energy balance of croplands and is a
      significant factor in crop growth monitoring and yield estimation. Precise
      determination of surface albedo is thus important. This study aimed to examine
      the influence of growth stages (tillering, jointing, heading, filling and
      maturity) on albedo and its diurnal asymmetry by measuring diurnal albedo
      variations. Results indicated that the daily mean surface albedo generally
      exhibited an increased tendency during tillering to heading but decreased after
      heading. Surface albedos were much higher in the morning than the corresponding
      values of the same solar elevation angles in the afternoon when the solar
      elevation angle was less than 40 degrees , indicating a diurnal asymmetry in
      surface albedo. However, less difference was found in surface albedos between
      forenoon and afternoon when the solar elevation angle was greater than 40 degrees
      . Dew droplets on the leaf surface in the morning were assumed to be the main
      factor resulting in the diurnal asymmetry in albedo of spring wheat.

PMID- 22392840
TI  - The pharmacotherapy implications of ventricular assist device in the patient with
      end-stage heart failure.
AB  - Advances in mechanical circulatory support, such as the use of ventricular assist
      devices (VADs), have become a means for prolonging survival in end-stage heart
      failure (HF). VADs decrease the symptoms of HF and improve quality of life by
      replacing some of the work of a failing heart. They unload the ventricle to
      provide improved cardiac output and end-organ perfusion, resulting in improvement
      in cardiorenal syndromes and New York Heart Association functional class rating.
      VADs are currently used asa bridge to heart transplantation, a bridge to recovery
      of cardiac function, or as destination therapy. Complications of VAD include
      bleeding, infections, arrhythmias, multiple organ failure, right ventricular
      failure, and neurological dysfunction. Patients with VAD have unique
      pharmacotherapeutic requirements in terms of anticoagulation, appropriate
      antibiotic selection, and continuation of HF medications. Pharmacists in acute
      care and community settings are well prepared to care for the patient with VAD.
      These patients require thorough counseling and follow-up with regard to
      prevention and treatment of infections, appropriate levels of anticoagulation,
      and maintenance of fluid balance. A basic understanding of this unique therapy
      can assist pharmacists in attending to the needs of patients with VAD.

PMID- 22392838
TI  - Rat bone marrow stromal cells-seeded porous gelatin/tricalcium
      phosphate/oligomeric proanthocyanidins composite scaffold for bone repair.
AB  - Repair of bone defects remains a major challenge in orthopaedic surgery. Bone
      tissue engineering is an attractive approach for treating bone loss in various
      shapes and amounts. The aim of this study was to prepare and evaluate the
      feasibility of a porous scaffold, which was composed of oligomeric
      proanthocyanidin crosslinked gelatin mixed with beta-tricalcium phosphate (GTP)
      and was seeded with bone marrow stromal cells (BMSCs) as a bone substitute. GTP
      scaffolds were made porous using a salt-leaching method. The physicochemical
      properties of the scaffold were evaluated to determine the optimal salt:composite
      weight ratio. The results indicated that the GTP scaffold had a favourable
      macroporous structure and higher porosity when the salt:composite weight ratio
      was 4:1. Cytotoxic tests demonstrated that extracts from the GTP scaffolds
      promoted the proliferation of BMSCs. Rat BMSCs were seeded on a GTP scaffold and
      cultured in a spinner flask. After 2 weeks of culture, scanning electron
      microscopy observation showed that the cells adhered well to the surfaces of the
      pores in the scaffold. Moreover, this study explored the biological response of
      rat calvarial bone to the scaffold to evaluate its potential in bone tissue
      engineering. Bone defects were filled with BMSC-seeded GTP scaffold and acellular
      GTP scaffold. After 8 weeks, the scaffold induced new bone formation at a bone
      defect, as was confirmed by X-ray microradiography and histology. The BMSC-seeded
      scaffold induced more new bone formation than did an acellular scaffold. These
      observations suggest that the BMSCs-seeded GTP scaffold can promote the
      regeneration of defective bone tissue.

PMID- 22392841
TI  - Use of herbals as galactagogues.
AB  - With a substantial number of women using herbal products to augment their milk
      production, this article will review available literature illustrating efficacy
      and adverse effects of using these products. Embase, PubMed, and EBSCO (all
      databases) were searched from inception to June 2011 using terms such as
      ''galactagogue,'' ''galactogogue,'' ''herbal,'' and ''botanical'' and the search
      was subsequently narrowed to specific herbals by name. Additional articles were
      obtained from article reference lists. Supplemental information was obtained with
      Natural Standard. All abstracts retrieved were evaluated for relevance and
      germane articles were included. Numerous lactation-stimulating herbals have been
      identified in the literature with varying degrees of evidence,mostly anecdotal.
      Use of torbangun, milk thistle, and fenugreek may correlate with increased milk
      supply. Evidence regarding adverse effects, pharmacodynamic properties, and
      pharmacokinetic effects remains scarce. Despite the fact that postpartum women
      may turn to herbal galactagogues, scant clinical evidence exists to justify their
      effectiveness. Further clinical trials are needed in order to substantiate these
      findings.

PMID- 22392842
TI  - Design and synthesis of piezochromic materials based on push-pull chromophores: a
      mechanistic perspective.
AB  - Computational analysis predicts that intramolecular charge transfer (ICT) exists
      in anthraquinone imide (AQI) derivatives with electron-donating substituents at
      the 6-position, such as 4-methoxylphenyl, 4-N,N-dimethylaminophenyl, and
      thiophene. However, for those with electron-withdrawing ones, no clear ICT
      interaction could be observed. We predicted, on the basis of the simulation
      results, that AQI derivatives with electron-donating substituents would be
      piezochromic. To verify this hypothesis, the corresponding AQI derivatives with
      various substituents were synthesized. Absorption spectra recorded with a diffuse
      reflectance method on powders revealed that 4-methoxylphenyl-, 4-N,N
      dimethylaminophenyl-, and thiophene-substituted AQI exhibited piezochromism, but
      not 4-nitrophenyl-substituted AQI, which is in good agreement with the simulation
      results. Interestingly, redshifts of both the lower and higher energy absorption
      bands were observed along with redshifts of the emission spectra. However, XRD
      patterns before and after being pressed presented no significant changes, which
      was different from known piezochromic molecules described in the literature. An
      unprecedented mechanism in which enhanced ICT from better conjugation between the
      donor and acceptor segments induced by the decrease of theta under pressure could
      be responsible for the piezochromism of aryl-substituted AQIs is proposed.

PMID- 22392843
TI  - Knowledge engineering for health: a new discipline required to bridge the "ICT
      gap" between research and healthcare.
AB  - Despite vast amount of money and research being channeled toward biomedical
      research, relatively little impact has been made on routine clinical practice. At
      the heart of this failure is the information and communication technology "chasm"
      that exists between research and healthcare. A new focus on "knowledge
      engineering for health" is needed to facilitate knowledge transmission across the
      research-healthcare gap. This discipline is required to engineer the
      bidirectional flow of data: processing research data and knowledge to identify
      clinically relevant advances and delivering these into healthcare use;
      conversely, making outcomes from the practice of medicine suitably available for
      use by the research community. This system will be able to self-optimize in that
      outcomes for patients treated by decisions that were based on the latest research
      knowledge will be fed back to the research world. A series of meetings,
      culminating in the "I-Health 2011" workshop, have brought together
      interdisciplinary experts to map the challenges and requirements for such a
      system. Here, we describe the main conclusions from these meetings. An "I4Health"
      interdisciplinary network of experts now exists to promote the key aims and
      objectives, namely "integrating and interpreting information for individualized
      healthcare," by developing the "knowledge engineering for health" domain.

PMID- 22392844
TI  - Improved MR phase-contrast velocimetry using a novel nine-point balanced motion
      encoding scheme with increased robustness to eddy current effects.
AB  - Phase-contrast MRI (PC-MRI) velocimetry is a noninvasive, high-resolution motion
      assessment tool. However, high motion sensitivity requires strong motion-encoding
      magnetic gradients, making phase-contrast-MRI prone to baseline shift artifacts
      due to the generation of eddy currents. In this study, we propose a novel nine
      point balanced velocity-encoding strategy, designed to be more accurate in the
      presence of strong and rapidly changing gradients. The proposed method was
      validated using a rotating phantom, and its robustness and precision were
      explored and compared with established approaches through computer simulations
      and in vivo experiments. Computer simulations yielded a 39-57% improvement in
      velocity-noise ratio (corresponding to a 27-33% reduction in measurement error),
      depending on which method was used for comparison. Moreover, in vivo experiments
      confirmed this by demonstrating a 26-53% reduction in accumulated velocity error
      over the R-R interval. The nine-point balanced phase-contrast-MRI-encoding
      strategy is likely useful for settings where high spatial and temporal resolution
      and/or high motion sensitivity is required, such as in high-resolution rodent
      myocardial tissue phase mapping.

PMID- 22392845
TI  - Novel extraneural role of neurite outgrowth inhibitor A: modulation of
      osteoclastogenesis via positive feedback regulation of nuclear factor of
      activated T cell cytoplasmic 1.
AB  - Osteoclasts are bone-resorbing cells differentiated from macrophage/monocyte
      lineage precursors upon receptor activator of NF-kappaB ligand (RANKL)
      stimulation. In a proteomic approach to identify proteins involved in
      osteoclastogenesis, we observed a dramatic increase in the expression of neurite
      outgrowth inhibitor A (Nogo-A) upon RANKL stimulation of mouse bone marrow
      macrophages (BMMs) in a nuclear factor of activated T cell cytoplasmic 1 (NFATc1)
      dependent manner. The knockdown of Nogo-A in BMMs significantly reduced RANKL
      dependent osteoclast differentiation accompanied by diminished NFATc1 induction,
      suggesting that a positive feedback mechanism is involved. Conversely, Nogo-A
      overexpression in BMMs as well as in RAW264.7 macrophages greatly augmented
      osteoclastogenesis, with concomitant increase in the NFATc1 induction. Both the
      mitogen-activated protein kinase (MAPK) pathway and calcium oscillation, which
      are central to RANKL-dependent NFATc1 activation and induction, were enhanced by
      Nogo-A. Finally, Nogo-A knockdown in mouse calvariae prevented interleukin 1 (IL
      1)-induced bone loss. These findings not only reveal an unprecedented extraneural
      role of Nogo-A in osteoclastogenesis but also suggest a novel drug target against
      bone-lytic diseases.

PMID- 22392847
TI  - The temperature dependence of Cr3+:YAG zero-phonon lines.
AB  - This paper deals with the photoluminescence temperature dependence of the zero
      phonon lines of Cr(3+) ions in an yttrium aluminium garnet (YAG) matrix.
      Experimental data were analysed in the framework of electron-phonon coupling in
      the quadratic approximation and it was found that Cr(3+) ions in the YAG matrix
      are strongly coupled with lattice vibrations, with a Debye temperature of about
      550 K and a value of the quadratic coupling constant of 0.65. The analysis of
      both homogeneous and inhomogeneous contributions to the photoluminescence
      linewidth is performed and the results obtained are compared with previously
      reported data for Fe(3+):YAG and discussed with respect to the different
      dependences of the two transition metal ions on the crystal field.

PMID- 22392848
TI  - Sequential, kinetically controlled synthesis of multicomponent stereoisomeric
      assemblies.

PMID- 22392846
TI  - In vivo assessment of age-related brain iron differences by magnetic field
      correlation imaging.
AB  - PURPOSE: To assess a recently developed magnetic resonance imaging (MRI)
      technique called magnetic field correlation (MFC) imaging along with a
      conventional imaging method, the transverse relaxation rate (R2), for estimating
      age-related brain iron concentration in adolescents and adults. Brain region
      measures were compared with nonheme iron concentrations (C(PM) ) based on a prior
      postmortem study. MATERIALS AND METHODS: Asymmetric spin echo (ASE) images were
      acquired at 3T from 26 healthy individuals (16 adolescents, 10 adults). Regions
      of interest (ROIs) were placed in areas in which age-related iron content was
      estimated postmortem: globus pallidus (GP), putamen (PUT), caudate nucleus (CN),
      thalamus (THL), and frontal white matter (FWM). Regression and group analyses
      were conducted on ROI means. RESULTS: MFC and R2 displayed significant linear
      relationships to C(PM) when all regions were combined. Whereas MFC was
      significantly correlated with C(PM) for every individual region except FWM and
      detected significantly lower means in adolescents than adults for each region, R2
      detected significant correlation and lower means for only PUT and CN. CONCLUSION:
      Our results support the hypothesis that MFC is sensitive to brain iron in GM
      regions and detects age-related iron increases known to occur from adolescence to
      adulthood. MFC may be more sensitive than R2 to iron-related changes occurring
      within specific brain regions.

PMID- 22392849
TI  - Effect of monocytes/macrophages on the early osteogenic differentiation of
      hBMSCs.
AB  - Heterotypic cell interactions are essential for the homeostasis of bone tissue,
      in particular the widely studied interaction between osteoblasts and osteoclasts.
      Closely related with osteoclasts are monocytes/macrophages. These have been shown
      to produce osteogenic factors, e.g. BMP-2, which plays a key role in bone
      metabolism. However, the mechanisms through which monocytes/macrophages interact
      with osteoblasts are still elusive. The aim of this work was to assess the
      influence of human peripheral blood monocytes/macrophages over the early
      osteogenic differentiation of human bone marrow stromal cells (hBMSCs) in the
      presence of dexamethasone-supplemented medium. The co-cultures were performed
      using porous transwells that allowed the interaction between both cell types
      through the production of paracrine factors. The potential effect of BMP-2
      produced by monocytes/macrophages was addressed by adding an anti-BMP-2 antibody
      to the co-cultures. hBMSCs cultured in the presence of monocytes/macrophages had
      a higher proliferation rate than hBMSCs monocultures. The quantification of early
      osteogenic marker alkaline phosphatase (ALP) revealed higher activity of this
      enzyme in cells in the co-culture throughout the time of culture. Both of these
      effects were inhibited by adding an anti-BMP-2 antibody to the cultures.
      Moreover, qRT-PCR for osteocalcin and osteopontin transcripts showed
      overexpression of both markers. Once again, the effect of monocytes/macrophages
      over hBMSC osteogenic differentiation was completely inhibited in the co-cultures
      by blocking BMP-2. The present report confirmed that monocytes/macrophages
      produce BMP-2, which promotes osteogenic differentiation and proliferation of
      hBMSCs cumulatively to dexamethasone-supplemented medium. This potentially
      implies that monocyte/macrophages play a stronger role in bone homeostasis than
      so far supposed.

PMID- 22392850
TI  - [MUW researcher of the month].

PMID- 22392854
TI  - An improved route to (+)-tedanolide and analysis of its subtle effects
      controlling conformation and biological behaviour.
AB  - The improved synthesis of the antitumor compound (+)-tedanolide is described
      through an aldol coupling of bis-ketone 7. This modification shortens the
      synthetic steps in the endgame and provides rapid access to this biologically
      important natural product. Additionally, it serves as a probe in order to unravel
      the conformational effects that impede or enable its successful synthesis. Having
      this way access to des-epoxy-tedanolide, its biological characterization
      surprisingly unravelled the mode of action to resemble candidaspongiolide rather
      than deoxytedanolide.

PMID- 22392855
TI  - Micro- and nanostructures of iridescent wing scales in purple emperor butterflies
      (Lepidoptera: Apatura ilia and A. iris).
AB  - Apatura ilia (Denis and Schiffermuller, 1775) and A. iris (Linnaeus, 1758) are
      fascinating butterflies found in the Palaearctic ecozone (excepting the north of
      Africa). The wings of these insects are covered with a great number of two types
      of scales positioned like roof tiles. Type I scales are on the surface, while
      type II scales are situated below them. The structural color of the type I scales
      is recognized only on the dorsal side of both the fore and hind wings of the
      males of the aforementioned species. Both types of scales are responsible for
      pigment color of the wings, but iridescence is observed only in the type I
      scales. The brilliant structural color is due to a multilayer structure. The
      features of the scales, their dimensions and fine structure were obtained using
      scanning electron microscopy. Cross sections of the scales were then analyzed by
      transmission electron microscopy. The scales of the "normal" and clytie forms of
      A. ilia have a different nanostructure, but are of the same type. A similar type
      of structure, but with a different morphology, was also noticed in A. iris. The
      scales of the analyzed species resemble the scales of tropical Morpho
      butterflies.

PMID- 22392856
TI  - Hybrid proton resonance frequency/T1 technique for simultaneous temperature
      monitoring in adipose and aqueous tissues.
AB  - Thermal therapy procedures being carried out under MR guidance would be safer if
      temperature changes could be accurately monitored in both water-based and fat
      based tissues. To this end, we present a hybrid proton resonance frequency
      (PRF)/T(1) approach for simultaneously measuring PRF shift temperatures in water
      based tissues and T(1) changes in fat-based tissues. The hybrid PRF/T(1) sequence
      is a standard radiofrequency spoiled gradient echo sequence executed in a dynamic
      mode with two flip angles alternating every time frame. The PRF information is
      extracted every time frame using the image phase in the standard approach, and
      the T(1) information is extracted every two time frames using a variable flip
      angle approach. Simulation studies, ex vivo high intensity focused ultrasound
      heating experiments, and in vivo stability experiments were performed to test the
      feasibility of the approach. The results indicate that the hybrid PRF/T(1)
      approach provides PRF temperature maps of the same quality as those obtained by
      traditional PRF methods while simultaneously being able to track T(1) changes in
      fat-based tissues. Although several potential error sources exist for the T(1)
      measurements, the approach is a promising start toward realizing quantitative
      temperature measurements in both water-based and fat-based tissues.

PMID- 22392857
TI  - Modeling impurity-assisted chain creation in noble-metal break junctions.
AB  - In this work we present the generalization of the model for chain formation in
      break junctions, introduced by Thiess et al (2008 Nano Lett. 8 2144), to zigzag
      transition-metal chains with s and p impurities. We apply this extended model to
      study the producibility trends for noble-metal chains with impurities, often
      present in break junction experiments, namely, Cu, Ag and Au chains with H, C, O
      and N adatoms. Providing the material-specific parameters for our model from
      systematic full-potential linearized augmented plane-wave first-principles
      calculations, we find that the presence of such impurities crucially affects the
      binding properties of the noble-metal chains. We reveal that both the impurity
      induced bond strengthening and the formation of zigzag bonds can lead to a
      significantly enhanced probability for chain formation in break junctions.

PMID- 22392858
TI  - Rough endoplasmic reticulum trafficking errors by different classes of mutant
      dentin sialophosphoprotein (DSPP) cause dominant negative effects in both
      dentinogenesis imperfecta and dentin dysplasia by entrapping normal DSPP.
AB  - Families with nonsyndromic dentinogenesis imperfecta (DGI) and the milder, dentin
      dysplasia (DD), have mutations in one allele of the dentin sialophosphoprotein
      (DSPP) gene. Because loss of a single Dspp allele in mice (and likely, humans)
      causes no dental phenotype, the mechanism(s) underling the dominant negative
      effects were investigated. DSPP mutations occur in three classes. (The first
      class, the mid-leader missense mutation, Y6D, was not investigated in this
      report.) All other 5' mutations of DSPP result in changes/loss in the first three
      amino acids (isoleucine-proline-valine [IPV]) of mature DSPP or, for the A15V
      missense mutation, some retention of the hydrophobic leader sequence. All of this
      second class of mutations caused mutant DSPP to be retained in the rough
      endoplasmic reticulum (rER) of transfected HEK293 cells. Trafficking out of the
      rER by coexpressed normal DSPP was reduced in a dose-responsive manner, probably
      due to formation of Ca2+-dependent complexes with the retained mutant DSPP. IPV
      like sequences begin many secreted Ca2+-binding proteins, and changing the third
      amino acid to the charged aspartate (D) in three other acidic proteins also
      caused increased rER accumulation. Both the leader-retaining A15V and the long
      string of hydrophobic amino acids resulting from all known frameshift mutations
      within the 3'-encoded Ca2+-binding repeat domain (third class of mutations)
      caused retention by association of the mutant proteins with rER membranes. More
      5' frameshift mutations result in longer mutant hydrophobic domains, but the
      milder phenotype, DD, probably due to lower effectiveness of the remaining,
      shorter Ca2+-binding domain in capturing normal DSPP protein within the rER. This
      study presents evidence of a shared underlying mechanism of capturing of normal
      DSPP by two different classes of DSPP mutations and offers an explanation for the
      mild (DD-II) versus severe (DGI-II and III) nonsyndromic dentin phenotypes.
      Evidence is also presented that many acidic, Ca2+-binding proteins may use the
      same IPV-like receptor/pathway for exiting the rER.

PMID- 22392859
TI  - Correlation of perfusion parameters on dynamic contrast-enhanced MRI with
      prognostic factors and subtypes of breast cancers.
AB  - PURPOSE: To investigate whether a correlation exists between perfusion parameters
      obtained from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI)
      and prognostic factors or immunohistochemical subtypes of breast cancers.
      MATERIALS AND METHODS: Quantitative parameters (K(trans) , k(ep) , and v(e) ) of
      70 invasive ductal carcinomas were obtained using DCE-MRI as a postprocessing
      procedure. Correlations between parameters and prognostic factors, including
      tumor size, axillary nodal status, histologic grade, nuclear grade, expression of
      estrogen receptor (ER), progesterone receptor (PR), Ki-67, p53, bcl-2, and human
      epidermal growth factor receptor 2 (HER2) and subtypes categorized as luminal (ER
      or PR-positive), triple negative (ER or PR-negative, HER2-negative), and HER2 (ER
      and PR-negative, HER2 overexpression) were analyzed. RESULTS: Mean K(trans) was
      higher in tumors with a high histologic grade than with a low histologic grade (P
      = 0.007), with a high nuclear grade than with a low nuclear grade (P = 0.002),
      and with ER negativity than ER positivity (P = 0.056). Mean k(ep) was higher in
      tumors with a high histologic grade than with a low histologic grade (P = 0.005),
      with a high nuclear grade than with a low nuclear grade (P = 0.001), and with ER
      negativity than with ER positivity (P = 0.043). Mean v(e) was lower in tumors
      with a high histologic grade than with a low histologic grade (P = 0.038) and
      with ER negativity than with ER positivity (P = 0.015). Triple-negative cancers
      showed a higher mean k(ep) than the luminal type (P = 0.015). CONCLUSION: Breast
      cancers with higher K(trans) and k(ep) , or lower v(e) , had poor prognostic
      factors and were often of the triple-negative subtype.

PMID- 22392860
TI  - Rubidium polyhydrides under pressure: emergence of the linear H3(-) species.
AB  - The structures of compressed rubidium polyhydrides, RbH(n) with n>1, and their
      evolution under pressure are studied using density functional theory
      calculations. These phases, which start to stabilize at only P = 2 GPa, consist
      of Rb(+) cations and one or more of the following species: H(-) anions, H(2)
      molecules, and H(3)(-) molecules. The latter motif, the simplest example of a
      three-center four-electron bond, is found in the most stable structures, RbH(5)
      and RbH(3) , which metallize above 200 GPa. At the highest pressures studied, our
      evolutionary searches find an RbH(6) phase which contains polymeric (H(3)(
      ))(infinity) chains that show signs of one-dimensional liquid-like behavior.

PMID- 22392861
TI  - The pace of prosodic phrasing couples the listener's cortex to the reader's
      voice.
AB  - We studied online coupling between a reader's voice and a listener's cortical
      activity using a novel, ecologically valid continuous listening paradigm. Whole
      scalp magnetoencephalographic (MEG) signals were recorded from 10 right-handed,
      native French-speaking listeners in four conditions: a female (Exp1f) and a male
      (Exp1m) reading the same text in French; a male reading a text in Finnish (Exp
      2), a language incomprehensible for the subjects, and a male humming Exp1 text
      (Exp 3). The fundamental frequency (f0) of the reader's voice was recorded with
      an accelerometer attached to the throat, and coherence was computed between f0
      time-course and listener's MEG. Similar levels of right-hemisphere-predominant
      coherence were found at ~0.5 Hz in Exps 1-3. Dynamic imaging of coherent sources
      revealed that the most coherent brain regions were located in the right posterior
      superior temporal sulcus (pSTS) and posterior superior temporal gyrus (pSTG) in
      Exps 1-2 and in the right supratemporal auditory cortex in Exp 3. Comparison
      between speech rhythm and phrasing suggested a connection of the observed
      coherence to pauses at the sentence level both in the spoken and hummed text.
      These results demonstrate significant coupling at ~0.5 Hz between reader's voice
      and listener's cortical signals during listening to natural continuous voice. The
      observed coupling suggests that voice envelope fluctuations, due to prosodic
      rhythmicity at the phrasal and sentence levels, are reflected in the listener's
      cortex as rhythmicity of about 2-s cycles. The predominance of the coherence in
      the right pSTS and pSTG suggests hemispherical asymmetry in processing of speech
      sounds at subsentence time scales.

PMID- 22392862
TI  - Acute coronary events.

PMID- 22392864
TI  - What cost weight loss?

PMID- 22392863
TI  - Lifestyle modification for obesity: new developments in diet, physical activity,
      and behavior therapy.

PMID- 22392865
TI  - Obesity and cardiovascular disease.

PMID- 22392866
TI  - Isolated anomalous right coronary artery from the pulmonary artery in adulthood:
      anatomical features and ischemic burden.

PMID- 22392867
TI  - Peripheral phenomena in a woman with calcinosis, raynaud phenomenon, esophageal
      dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome-associated
      pulmonary hypertension.

PMID- 22392868
TI  - Iatrogenic aortic dissection ... or intramural hematoma?

PMID- 22392870
TI  - Letter by McGuire and Aguilar regarding article, "Effect of torcetrapib on
      glucose, insulin, and hemoglobin A1c in subjects in the investigation of lipid
      level management to understand its impact in atherosclerotic events (ILLUMINATE)
      trial".

PMID- 22392871
TI  - Letter by Knop regarding article, "Effect of torcetrapib on glucose, insulin, and
      hemoglobin A1c in subjects in the investigation of lipid level management to
      understand its impact in atherosclerotic events (ILLUMINATE) trial".

PMID- 22392872
TI  - Letter by Fayssoil regarding article, "Early treatment with lisinopril and
      spironolactone preserves cardiac and skeletal muscle in Duchenne muscular
      dystrophy mice".

PMID- 22392873
TI  - Catalytic enantioselective alkene aminohalogenation/cyclization involving atom
      transfer.
AB  - Problem solved: the title reaction was used for the synthesis of chiral 2-bromo,
      chloro, and iodomethyl indolines and 2-iodomethyl pyrrolidines. Stereocenter
      formation is believed to occur by enantioselective cis aminocupration and C-X
      bond formation is believed to occur by atom transfer. The ultility of the
      products as versatile synthetic intermediates was demonstrated, as was a radical
      cascade cyclization sequence.

PMID- 22392874
TI  - Magnetic structure of the ferromagnetic new ternary silicide Nd5CoSi2.
AB  - Nd(5)CoSi(2) was obtained from the elements by arc-melting followed by annealing
      at 883 K. Its investigation by single-crystal x-ray and neutron powder
      diffraction shows that this ternary silicide crystallizes as Nd(5)Si(3) in a
      tetragonal structure deriving from the Cr(5)B(3)-type (I4/mcm space group; a =
      7.7472(2) and c = 13.5981(5) A as unit cell parameters). The structural
      refinements confirm the mixed occupancy on the 8h site between Si and Co atoms,
      as already observed for Gd(5)CoSi(2). Magnetization and specific heat
      measurements reveal a ferromagnetic behavior below T(C) = 55 K for Nd(5)CoSi(2).
      This magnetic ordering is further evidenced by neutron powder diffraction
      investigation revealing between 1.8 K and T(C) a canted ferromagnetic structure
      in the direction of the c-axis described by a propagation vector k = (0 0 0). At
      1.8 K, the two Nd(3+) ions carry ordered magnetic moments equal respectively to
      1.67(7) and 2.37(7) MU(B) for Nd1 and Nd2; these two moments exhibit a canting
      angle of theta = 4.3(6) degrees . This magnetic structure presents some
      similarities with that reported for Nd(5)Si(3).

PMID- 22392875
TI  - Plasma phosphatidylcholine concentrations of polyunsaturated fatty acids are
      differentially associated with hip bone mineral density and hip fracture in older
      adults: the Framingham Osteoporosis Study.
AB  - Polyunsaturated fatty acids (PUFAs) may influence bone health. The objective of
      this work was to examine associations between plasma phosphatidylcholine (PC)
      PUFA concentrations and hip measures: (1) femoral neck bone mineral density (FN
      BMD) (n = 765); (2) 4-year change in FN-BMD (n = 556); and (3) hip fracture risk
      (n = 765) over 17-year follow-up among older adults in the Framingham
      Osteoporosis Study. BMD measures were regressed on quintile of plasma PC PUFAs
      (docosahexaenoic acid [DHA], linoleic acid [LA], and arachidonic acid [AA]),
      adjusted for covariates. Hazard ratios (HR) and 95% confidence interval (CI) for
      hip fracture were estimated by quintile of plasma PC PUFAs, adjusted for
      covariates. Higher concentrations of PC DHA were associated with loss of FN-BMD
      over 4 years in women (p-trend = 0.04), but was protective in men in the
      uppermost quintile compared to men grouped in the lower four quintiles, in post
      hoc analysis (p = 0.01). PC LA concentrations were inversely associated with
      baseline FN-BMD in women (p-trend = 0.02), and increased hip fracture risk in
      women and men (p-trend = 0.05), but body mass index (BMI) adjustment attenuated
      these associations (p-trend = 0.12 and p-trend = 0.14, respectively). A trend
      toward a protective association was observed between PC AA and baseline FN-BMD in
      men (p-trend = 0.06). Women and men with the highest PC AA concentrations had 51%
      lower hip fracture risk than those with the lowest (HR = 0.49, 95% CI = 0.24
      1.00). Opposing effects of PC DHA on FN-BMD loss observed in women and men need
      further clarification. Bone loss associated with PC LA may be confounded by BMI.
      High PC AA concentrations may be associated with reduced hip fracture risk.

PMID- 22392877
TI  - Angiotensin-converting enzyme I/D polymorphism is not associated with type 2
      diabetes in a Chinese population.
AB  - OBJECTIVE: A role for the angiotensin-converting enzyme (ACE) gene has been
      suggested in the aetiology of type 2 diabetes (T2DM). However, results have been
      inconsistent. In this study, we performed a meta-analysis to further clarify the
      association between ACE I/D polymorphism and T2DM risk in a Chinese population.
      METHODS: PubMed, EMBASE, CNKI and Wan Fang Data were searched for eligible
      studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were
      calculated using a fixed-effects model or random-effects model. RESULTS: : A
      total of 41 studies (4708 cases and 5368 controls) for the association between
      ACE I/D polymorphism and T2DM in a Chinese population were identified. The pooled
      ORs for the association between ACE I/D polymorphism and T2DM risk were not
      statistically significant under all genetic models (co-dominant model: DD vs. II:
      OR = 1.17, 95% CI 0.97-1.42 and ID vs. II: OR = 1.01, 95% CI 0.93-1.10; dominant
      model: OR = 1.06, 95% CI 0.94-1.19; multiplicative model: OR = 1.08, 95% CI 0.98
      1.18). Although a marginally significant association was observed under a
      recessive model (OR = 1.17, 95% CI 1.00-1.36), robustness of this estimate could
      not be established under additional sensitivity analyses. CONCLUSIONS: : The meta
      analysis presented in this study indicated that ACE I/D polymorphism may not be
      associated with the risk of T2DM in the Chinese population.

PMID- 22392876
TI  - Correction of arterial input function in dynamic contrast-enhanced MRI of the
      liver.
AB  - PURPOSE: To develop a postprocessing method to correct saturation of arterial
      input function (AIF) in T1-weighted dynamic contrast-enhanced magnetic resonance
      imaging (DCE-MRI) for quantification of hepatic perfusion. MATERIALS AND METHODS:
      The saturated AIF is corrected by parameterizing the first pass of the AIF as a
      smooth function with a single peak and minimizing a least-squares error in
      fitting the liver DCE-MRI data to a dual-input single-compartment model.
      Sensitivities of the method to the degree of saturation in the AIF first-pass
      peak and the image contrast-to-noise ratio were assessed. The method was also
      evaluated by correlating portal venous perfusion with an independent overall
      liver function measurement. RESULTS: The proposed method corrects the distorted
      AIF with a saturation ratio up to 0.45. The corrected AIF improved hepatic
      arterial perfusion by -23.4% and portal venous perfusion by 26.9% in a study of
      12 patients with liver cancers. The correlation between the mean voxelwise portal
      venous perfusion and overall liver function measurement was improved by using the
      corrected AIFs (R(2) = 0.67) compared with the saturated AIFs (R(2) = 0.39).
      CONCLUSION: The method is robust for correcting AIF distortion and has the
      potential to improve quantification of hepatic perfusion for assessment of liver
      tissue response to treatment in patients with hepatic cancers.

PMID- 22392878
TI  - Synergistic effect of angiotensin II type-1 receptor 1166A/C with angiotensin
      converting enzyme polymorphism on risk of acute myocardial infarction in north
      Indians.
AB  - INTRODUCTION: This first study from north India investigated the synergistic
      effect of AT1R 1166A/C with the ACE I/D polymorphism on risk of acute myocardial
      infarction (AMI). MATERIALS AND METHODS: Traditional coronary risk factors, ACE
      I/D and AT1R 1166A/C polymorphism were analyzed in 350 patients with AMI and 350
      matched controls. RESULTS: In univariate analysis, hypertension (52.9% vs. 11.1%;
      OR=8.9; 95%CI 6.0-13.3), diabetes mellitus (16.0% vs. 0.6%; OR=33.1; 95%CI 8.0
      137), smoking (43.7% vs. 20.9%; OR=2.9; 95%CI 2.1-4.1), family history of
      coronary artery disease (22.3% vs. 14.0%; OR=1.8; 95%CI 1.2-2.6), high body mass
      index (64.3% vs. 51.4%; OR=1.7; 95%CI 1.3-2.3), high waist-hip ratio (46.2% vs.
      2.3%; OR=37; 95%CI 16-85.8) and AT1R 1166AC genotype (20.6% vs. 12%; OR=1.9;
      95%CI 1.3-2.9) were associated with AMI. In multivariate analysis, all these
      factors were found to be independent risk predictors for AMI. Subjects carrying
      the AT1R 1166AC+CC and ACE ID+DD combined genotype showed a twofold increased
      association (OR=2.1; 95%CI 1.2-3.5) compared with the AT1R 1166AA-ACE II combined
      genotype. Patients who smoked and who carried the ACE ID+DD genotype had 2.4-fold
      (OR=2.4; 95%CI 1.5-3.8), and with the AT1R 1166AC+CC genotype had 15-fold
      (OR=14.9; 95%CI 5.2-42.8) increased risk of AMI compared with non-smoking non
      carriers. CONCLUSIONS: The AT1R 1166A/C polymorphism has association with AMI
      among north Indian patients, particularly if integrated with ACE I/D polymorphism
      and smoking.

PMID- 22392879
TI  - "Spontaneous" ambient temperature dehydrocoupling of aromatic amine-boranes.
AB  - The dehydrocoupling/dehydrogenation behavior of primary arylamine-borane adducts
      ArNH(2)?BH(3) (3 a-c; Ar = a: Ph, b: p-MeOC(6)H(4), c: p-CF(3)C(6)H(4)) has been
      studied in detail both in solution at ambient temperature as well as in the solid
      state at ambient or elevated temperatures. The presence of a metal catalyst was
      found to be unnecessary for the release of H(2). From reactions of 3 a,b in
      concentrated solutions in THF at 22  degrees C over 24 h cyclotriborazanes (ArNH
      BH(2))(3) (7 a,b) were isolated as THF adducts, 7 a,b?THF, or solvent-free 7 a,
      which could not be obtained via heating of 3 a-c in the melt. The MU
      (anilino)diborane [H(2)B(MU-PhNH)(MU-H)BH(2)] (4 a) was observed in the reaction
      of 3 a with BH(3)?THF and was characterized in situ. The reaction of 3 a with
      PhNH(2) (2 a) was found to provide a new, convenient method for the preparation
      of dianilinoborane (PhNH)(2)BH (5 a), which has potential generality. This
      observation, together with further studies of reactions of 4 a, 5 a, and 7 a,b,
      provided insight into the mechanism of the catalyst-free ambient temperature
      dehydrocoupling of 3 a-c in solution. For example, the reaction of 4 a with 5 a
      yields 6 a and 7 a. It was found that borazines (ArN-BH)(3) (6 a-c) are not
      simply formed via dehydrogenation of cyclotriborazanes 7 a-c in solution. The
      transformation of 7 a to 6 a is slowly induced by 5 a and proceeds via
      regeneration of 3 a. The adducts 3 a-c also underwent rapid dehydrocoupling in
      the solid state at elevated temperatures and even very slowly at ambient
      temperature. From aniline-borane derivative 3 c, the linear iminoborane oligomer
      (p-CF(3)C(6)H(4))N[BH-NH(p-CF(3)C(6)H(4))](2) (11) was obtained. The single
      crystal X-ray structures of 3 a-c, 5 a, 7 a, 7 b?THF, and 11 are discussed.

PMID- 22392881
TI  - Hidden Markov analysis of trajectories in single-molecule experiments and the
      effects of missed events.
AB  - The ever more complex fluctuation patterns discovered by single molecule
      experiments require statistical methods to analyze multi-state hopping traces of
      long lengths. Hidden Markov modeling is a statistical tool that offers the
      scalability to analyze even complex data and extract kinetic information. We give
      an introduction on how to implement hidden Markov modeling for the analysis of
      single molecule force spectroscopic traces, deal with missed events, and test the
      method on a calcium binding protein.

PMID- 22392880
TI  - Hexapeptide fragment of carcinoembryonic antigen which acts as an agonist of
      heterogeneous ribonucleoprotein M.
AB  - Colorectal cancers with metastatic potential secrete the glycoprotein
      carcinoembryonic antigen (CEA). CEA has been implicated in colorectal cancer
      metastasis by inducing Kupffer cells to produce inflammatory cytokines which, in
      turn, make the hepatic micro-environment ideal for tumor cell implantation. CEA
      binds to the heterogeneous ribonucleoprotein M (hnRNP M) which acts as a cell
      surface receptor in Kupffer cells. The amino acid sequence in CEA, which binds
      the hnRNP M receptor, is Tyr-Pro-Glu-Leu-Pro-Lys. In this study, the structure of
      Ac-Tyr-Pro-Glu-Leu-Pro-Lys-NH2 (YPELPK) was investigated using electronic
      circular dichroism, vibrational circular dichroism, and molecular dynamics
      simulations. The binding of the peptide to hnRNP M was also investigated using
      molecular docking calculations. The biological activity of YPELPK was studied
      using differentiated human THP-1 cells, which express hnRNP M on their surface
      and secrete IL-6 when stimulated by CEA. YPELPK forms a stable polyproline-II
      helix and stimulates IL-6 production of THP-1 cells at micromolar concentrations.

PMID- 22392882
TI  - Use of thiazolidinediones and risk of osteoporotic fracture: disease or drugs?
AB  - PURPOSE: Clinical and observational studies suggest that use of
      thiazolidinediones (TZDs) is associated with an increased fracture risk. In
      addition, type 2 diabetes mellitus (T2DM) is a risk factor for osteoporotic
      fracture. Our aim was to estimate fracture risks in TZD users and users of other
      antidiabetic drugs, classified according to proxies of disease severity. METHODS:
      We conducted a population-based cohort study utilizing the Dutch PHARMO database
      (1998-2008). PHARMO links pharmacy-dispensing data to the National Hospital
      Registry. Oral antidiabetic users (n = 123,452) were matched 1:4 by year of birth
      and sex to non-users. Cox proportional hazards models were used to estimate
      hazard ratios (HRs) of fracture in TZD users. We created a proxy indicator for
      disease severity. The first stage was defined as current use of either a
      biguanide or a sulfonylureum, the second stage as current use of a biguanide and
      a sulfonylureum at the same time, the third stage was assigned to patients using
      TZDs and the fourth stage to patients using insulin. RESULTS: The risk of
      osteoporotic fracture was increased 1.5-fold (HR 1.49, 95%CI 1.28-1.73) in
      patients who currently used TZDs (stage 3), and for patients using insulin (stage
      4), the risk was increased 1.2-fold (HR 1.24, 1.14-1.36), as compared with
      controls. In the first and second stages, risks were lower: HR 1.11 (1.06-1.17)
      for stage 1 and HR 1.03 (0.96-1.11) for stage 2. CONCLUSIONS: When observational
      studies assess risk of fracture in patients with TZDs, the severity of T2DM
      should be taken into account.

PMID- 22392883
TI  - Aminopyrrolic synthetic receptors for monosaccharides: a class of carbohydrate
      binding agents endowed with antibiotic activity versus pathogenic yeasts.
AB  - The biological activity of a set of structurally related aminopyrrolic synthetic
      receptors for monosaccharides has been tested versus yeast and yeast-like
      microorganisms and compared to their binding affinity toward mannosides.
      Antibiotic activity comparable to that of well-known polyene (amphotericin B) or
      azole (ketoconazole) drugs has been found for some members of the family, along
      with a general correlation with binding abilities. A systematic structure
      activity-affinity investigation shed light on the structural and functional
      requirements necessary for antibiotic activity and identified the tripodal
      compound 1 as the most potent compound of the set. Together with toxicity tests
      and inhibitor localization experiments performed through fluorescence microscopy,
      these studies led to the characterization of a new class of carbohydrate binding
      agents possessing antibiotic activity, in which pyrrolic groups precisely
      structured on a tripodal architecture appear to be responsible for permeability
      through the cell wall of pathogens, as well as for antibiotic activity inside the
      cytoplasm.

PMID- 22392884
TI  - Pressure-induced colossal piezoresistance effect and the collapse of the
      polaronic state in the bilayer manganite (La(0.4)Pr(0.6))(1.2)Sr(1.8)Mn2O7.
AB  - We have investigated the effect of hydrostatic pressure as a function of
      temperature on the resistivity of a single crystal of the bilayer manganite
      (La(0.4)Pr(0.6))(1.2)Sr(1.8)Mn(2)O(7). Whereas a strong insulating behaviour is
      observed at all temperatures at ambient pressure, a clear transition into a
      metallic-like behaviour is induced when the sample is subjected to a pressure (P)
      of ~1.0 GPa at T < 70 K. A huge negative piezoresistance ~10(6) in the low
      temperature region at moderate pressures is observed. When the pressure is
      increased further (5.5 GPa), the high temperature polaronic state disappears and
      a metallic behaviour is observed. The insulator to metal transition temperature
      exponentially increases with pressure and the distinct peak in the resistivity
      that is observed at 1.0 GPa almost vanishes for P > 7.0 GPa. A modification in
      the orbital occupation of the e(g) electron between 3d(x(2)-y(2)) and 3d(z(2)
      r(2)) states, as proposed earlier, leading to a ferromagnetic double-exchange
      phenomenon, can qualitatively account for our data.

PMID- 22392885
TI  - Efficient formation of heterodimers from peptides and proteins using
      unsymmetrical polyfluorophenyl esters of dicarboxylic acids.
AB  - An efficient method for the heteroconjugation of biomolecules carrying free amino
      groups was reported previously, where mixed polyfluorophenyl diesters of
      dicarboxylic acids with varied aliphatic chain length were shown to be efficient
      reagents for the conjugation of a variety of model biomolecules. The concept was
      based on the differential reactivity of the esters towards amines. The concept
      has now been further optimized, and a 2,6-difluorophenyl-pentafluorophenyl
      diester combination has been demonstrated to be the most efficient, both with
      respect to selectivity and to reaction rate. A pentafluorophenyl ester reacts
      faster with an amino group and requires a weaker base than a 2,6-difluorophenyl
      ester that requires a stronger base and longer reaction time. With the use of
      this combination of esters, we obtained considerably shortened reaction times
      compared with those reported previously, yet still retaining the desired
      selectivity in heteroconjugation. The increased reactivity of the bifunctional
      reagent allowed the construction of sophisticated peptide heteroconjugates from
      peptides, carbohydrates and proteins, showing a wide scope of applicability in
      the field of assembling functional bioconjugates.

PMID- 22392886
TI  - Interfacial layering of a room-temperature ionic liquid thin film on mica: a
      computational investigation.
AB  - The structure of a thin (4 nm) [bmim][Tf(2)N] film on mica was studied by
      molecular dynamics simulations using an empirical force field. Interfacial
      layering at T=300 K and at T=350 K is investigated by determining the number- and
      charge-density profiles of [bmim][Tf(2)N] as a function of distance from mica,
      and by computing the normal force F(z) opposing the penetration of the ionic
      liquid film by a spherical nanometric tip interacting with [bmim][Tf(2)N] atoms
      by a short-range potential. The results show that layering is important but
      localised within ~1 nm from the interface. The addition of a surface charge on
      mica, globally neutralised by an opposite charge on the [bmim][Tf(2)N] side,
      gives rise to low-amplitude charge oscillations extending through the entire
      film. However, outside a narrow interfacial region, the resistance of the
      [bmim][Tf(2)N] film to penetration by the mesoscopic tip is only marginally
      affected by the charge at the interface. The results obtained here for
      [bmim][Tf(2)N]/mica are similar to those obtained using the same method for the
      [bmim][Tf(2)N]/silica interface, and agree well with experimental force-distance
      profiles measured on the latter interface at ambient conditions.

PMID- 22392887
TI  - The third analysis of cancer mortality among Japanese nuclear workers, 1991-2002:
      estimation of excess relative risk per radiation dose.
AB  - The present study estimated excess relative risk per sievert (ERR/Sv) of cancer
      mortality among the cohort of 200 583 male Japanese nuclear workers, with an
      average individual cumulative dose of 12.2 mSv (<10 mSv, 75.4%; 100 + mSv, 2.6%),
      conducting Poisson regression using dose category specific observed and expected
      numbers of deaths, and average doses obtained from the official report of the
      Radiation Effects Association (REA) on the analysis of mortality of Japanese
      nuclear industry workers for 1991-2002, which reported the estimates of ERR/Sv 
      for leukaemia but not for all cancers or any other cancer site. The possible
      confounding biases from drinking alcohol and smoking tobacco were evaluated by
      examining the association of cumulative radiation dose with the mortality of
      cancers related to drinking or smoking. For leukaemia (80 deaths), the estimate
      of ERR/Sv was - 1.93 (95% confidence interval (CI) = - 6.12, 8.57). For all
      cancers excluding leukaemia (2636 deaths), while the ERR/Sv was estimated to be
      1.26 (95%CI = - 0.27, 3.00), confounding by alcohol consumption was suspected
      since the ERR/Sv  estimate of alcohol-related cancers was 4.64 (95%CI = 1.13,
      8.91) and the ERR/Sv  estimate of all cancers excluding leukaemia and alcohol
      related cancers was 0.20 (95%CI = - 1.42, 2.09). In conclusion, confounding by
      important lifestyle factors related to cancer risk may have a substantial effect
      on risk estimates, especially when conducting studies of low cumulative dose and,
      accordingly, low statistical power. Pooled analysis or meta-analysis of nuclear
      workers for solid cancers needs to take this point into account.

PMID- 22392888
TI  - The beryllium pentamer: trailing an uneven sequence of dissociation energies.
AB  - Recent high-resolution spectroscopic studies by Merritt, Bondybey, and Heaven
      (Science 2009, 324, 1548) have heightened the anticipation that small beryllium
      clusters will soon be observed in the laboratory. Beryllium clusters are
      important discrete models for the theoretical study of metals. The trigonal
      bipyramidal Be(5) molecule is studied using high-level coupled cluster methods.
      We obtain the optimized geometry, atomization and dissociation energies, and
      vibrational frequencies. The c~CCSDT(Q) method is employed to compute the
      atomization and dissociation energies. In this approach, complete basis set (CBS)
      extrapolations at the CCSD(T) level of theory are combined with an additive
      correction for the effect of iterative triple and perturbative quadruple
      excitations. Harmonic vibrational frequencies are obtained using analytic
      gradients computed at the CCSD(T) level of theory. We report an atomization
      energy of 129.6 kcal mol(-1) at the trigonal bipyramid global minimum geometry.
      The Be(5)->Be(4)+Be dissociation energy is predicted to be 39.5 kcal mol(-1). The
      analogous dissociation energies for the smaller beryllium clusters are 64.0 kcal
      mol(-1) (Be(4)->Be(3)+Be), 24.2 kcal mol(-1) (Be(3)->Be(2)+Be), and 2.7 kcal mol(
      1) (Be(2)->Be+Be). The trigonal bipyramidal Be(5) structure has an equatorial
      equatorial bond length of 2.000 A and an axial-equatorial distance of 2.060 A.
      Harmonic frequencies of 730, 611, 456, 583, 488, and 338 cm(-1) are obtained at
      the CCSD(T)/cc-pCVQZ level of theory. Quadruple excitations are found to make
      noticeable contributions to the energetics of the pentamer, which exhibits a
      significant level of static correlation.

PMID- 22392889
TI  - Friendship predictors of global self-worth and domain-specific self-concepts in
      university students with and without learning disability.
AB  - This study investigated the association among friendship, global self-worth, and
      domain-specific self-concepts in 102 university students with and without
      learning disabilities (LD). Students with LD reported lower global self-worth and
      academic self-concept than students without LD, and this difference was greater
      for women. Students with LD also reported that they had more stable friendships
      than students without LD. Students with LD were more likely to have higher global
      self-worth and self-perceptions of social acceptance if they had stable
      friendships and had relationships where they communicated spontaneously and
      frankly. None of the friendship variables predicted academic self-concept. Thus,
      having stable and intimate friendships is a protective factor in relation to
      global self-worth and social self-concept in university students with LD. 

PMID- 22392891
TI  - Problem representation and mathematical problem solving of students of varying
      math ability.
AB  - The purpose of this study was to examine differences in math problem solving
      among students with learning disabilities (LD, n = 25), low-achieving students
      (LA, n = 30), and average-achieving students (AA, n = 29). The primary interest
      was to analyze the processes students use to translate and integrate problem
      information while solving problems. Paraphrasing, visual representation, and
      problem-solving accuracy were measured in eighth grade students using a
      researcher-modified version of the Mathematical Processing Instrument. Results
      indicated that both students with LD and LA students struggled with processing
      but that students with LD were significantly weaker than their LA peers in
      paraphrasing relevant information. Paraphrasing and visual representation
      accuracy each accounted for a statistically significant amount of variance in
      problem-solving accuracy. Finally, the effect of visual representation of
      relevant information on problem-solving accuracy was dependent on ability;
      specifically, for students with LD, generating accurate visual representations
      was more strongly related to problem-solving accuracy than for AA students.
      Implications for instruction for students with and without LD are discussed. 

PMID- 22392890
TI  - Prediction and stability of mathematics skill and difficulty.
AB  - The present study evaluated the stability of math learning difficulties over a 2
      year period and investigated several factors that might influence this stability
      (categorical vs. continuous change, liberal vs. conservative cut point, broad vs.
      specific math assessment); the prediction of math performance over time and by
      performance level was also evaluated. Participants were 144 students initially
      identified as having a math difficulty (MD) or no learning difficulty according
      to low achievement criteria in the spring of Grade 3 or Grade 4. Students were
      reassessed 2 years later. For both measure types, a similar proportion of
      students changed whether assessed categorically or continuously. However,
      categorical change was heavily dependent on distance from the cut point and so
      more common for MD, who started closer to the cut point; reliable change index
      change was more similar across groups. There were few differences with regard to
      severity level of MD on continuous metrics or in terms of prediction. Final math
      performance on a broad computation measure was predicted by behavioral
      inattention and working memory while considering initial performance; for a
      specific fluency measure, working memory was not uniquely related, and behavioral
      inattention more variably related to final performance, again while considering
      initial performance. 

PMID- 22392892
TI  - Learning and memory impairments in children and adolescents with attention
      deficit/hyperactivity disorder.
AB  - There are relatively few studies on learning and delayed memory with attention
      deficit/hyperactivity disorder (ADHD). The objective of the present study was to
      examine acquisition, free delayed memory, and recognition skills in medication
      naive children and adolescents aged 8-16 years with ADHD combined subtype (36
      participants) and inattentive subtype (45) compared to 50 healthy controls (HC)
      aged 8-17 years. Learning and delayed memory were assessed with the Hopkins
      Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised,
      which have compatible methods of administration, test format, and score ranges.
      The results showed that children with both ADHD subtypes scored significantly
      below HC in acquisition, free delayed memory, and recognition, even when
      controlling for the effect of IQ. Comparing phases in the learning process showed
      an initial deficit in acquisition but no increase in effect size in subsequent
      testing of free delayed memory or recognition. The study indicates that learning
      and delayed memory processes are impaired in both combined and inattentive
      subtypes of ADHD and that the deficits are not merely an artifact of IQ. The
      study indicates that emphasis must be put on the acquisition phase and how
      students with ADHD organize and encode new information. 

PMID- 22392893
TI  - Assessment of uncertainty associated with measuring exposure to radon and decay
      products in the French uranium miners cohort.
AB  - The reliability of exposure data directly affects the reliability of the risk
      estimates derived from epidemiological studies. Measurement uncertainty must be
      known and understood before it can be corrected. The literature on occupational
      exposure to radon ((222)Rn) and its decay products reveals only a few
      epidemiological studies in which uncertainty has been accounted for explicitly.
      This work examined the sources, nature, distribution and magnitude of uncertainty
      of the exposure of French uranium miners to radon ((222)Rn) and its decay
      products. We estimated the total size of uncertainty for this exposure with the
      root sum square (RSS) method, which may be an alternative when repeated measures
      are not available. As a result, we identified six main sources of uncertainty.
      The total size of the uncertainty decreased from about 47% in the period 1956
      1974 to 10% after 1982, illustrating the improvement in the radiological
      monitoring system over time.

PMID- 22392894
TI  - Low density lipoprotein receptor-related protein 1 modulates the proliferation
      and migration of human hepatic stellate cells.
AB  - Human hepatic stellate cells (HHSCs) proliferation and migration play a key role
      in the pathogenesis of liver inflammation and fibrogenesis. Low density
      lipoprotein receptor-related protein (LRP1) is an endocytic receptor involved in
      intracellular signal transduction. The aim of this work was to analyse the role
      of low density lipoprotein receptor-related protein (LRP1) in HHSCs proliferation
      and migration and the mechanisms involved. Human LRP1 deficient-HHSCs were
      generated by nucleofecting the line HHSCs with siRNA anti-LRP1. HHSCs DNA
      synthesis was measured by [(3) H]-thymidine incorporation and cell cycle
      progression by flow cytometry after annexin V and iodure propidium staining. Cell
      migration was assessed using a wound repair model system. LRP1 expression and
      extracellular matrix-regulated kinase (ERK1,2) phosphorylation were analysed by
      Western blot analysis. Transforming growth factor-beta (TGF-beta) extracellular
      levels were analysed by ELISA. siRNA-antiLRP1 treatment almost completely
      inhibited LRP1 mRNA and protein expression. LRP1 deficient HHSCs showed higher
      proliferative response (172 +/- 19 vs. 93 +/- 8 [(3) H]-thymidine incorporation;
      78.68% vs. 82.69% in G0/G1, 21.32% vs. 17.30% in G2/S) and higher migration rates
      than control HHSCs. LRP1 deficient cells showed higher levels of phosphorylated
      ERK1,2. TGF-beta extracellular levels were threefold higher in LRP1-deficient
      than in control HHSCs cells. These results demonstrate that LRP1 regulates HHSCs
      proliferation and migration through modulation of ERK1,2 phosphorylation and TGF
      beta extracellular levels. These results suggest that HHSCs-LRP1 may play a key
      role in the modulation of factors determining hepatic fibrosis.

PMID- 22392895
TI  - Photopolymerization inhibition dynamics for sub-diffraction direct laser writing
      lithography.
AB  - Selective inhibition of the polymerization leads to sub-diffraction feature sizes
      in direct writing lithography-a principle based on the idea of stimulated
      emission depletion (STED) microscopy. However, the detailed understanding of the
      inhibition process is a key point to further enhance the resolution of the
      system. The authors present experiments focused on the time dynamics of the
      inhibition process, clarifying possible photophysical pathways.

PMID- 22392896
TI  - Protein sequences involved in the mitochondrial import of the 3,5,3'-L
      triiodothyronine receptor p43.
AB  - The major effect of T3 on mitochondrial activity has been partly explained by the
      discovery of p43, a T3-dependent transcription factor of the mitochondrial
      genome. P43 is imported into mitochondria in an atypical manner which is not yet
      fully understood. Our aim was to characterize the p43 sequences inducing its
      mitochondrial import, using in organello import experiments with wild-type or
      mutated proteins and validation in CV1 cells. We find that several sequences
      define the mitochondrial addressing. Two alpha helices in the C-terminal part of
      p43 are actual mitochondrial import sequences as fusion to a cytosolic protein
      induces its mitochondrial translocation. Helix 5 drives the atypical
      mitochondrial import process, whereas helices 10/11 induce a classical import
      process. However, despite its inability to drive a mitochondrial import, the N
      terminal region of p43 also plays a permissive role as in the presence of the C
      terminal import sequences different N-terminal regions determine whether the
      protein is imported or not. These results can be extrapolated to other
      mitochondrial proteins related to the nuclear receptor superfamily, devoid of
      classical mitochondrial import sequences.

PMID- 22392897
TI  - Analogues of the frog skin peptide alyteserin-2a with enhanced antimicrobial
      activities against Gram-negative bacteria.
AB  - The emergence of strains of multidrug-resistant Gram-negative bacteria mandates a
      search for new types of antimicrobial agents. Alyteserin-2a
      (ILGKLLSTAAGLLSNL.NH2) is a cationic, alpha-helical peptide, first isolated from
      skin secretions of the midwife toad, Alytes obstetricans, which displays
      relatively weak antimicrobial and haemolytic activities. Increasing the
      cationicity of alyteserin-2a while maintaining amphipathicity by the substitution
      Gly11 -> Lys enhanced the potency against both Gram-negative and Gram-positive
      bacteria by between fourfold and 16-fold but concomitantly increased cytotoxic
      activity against human erythrocytes by sixfold (mean concentration of peptide
      producing 50% cell death; LC50=24 uM). Antimicrobial potency was increased
      further by the additional substitution Ser7 ->Lys, but the resulting analogue
      remained cytotoxic to erythrocytes (LC50=38 uM). However, the peptide containing
      D-lysine at positions 7 and 11 showed high potency against a range of Gram
      negative bacteria, including multidrug-resistant strains of Acinetobacter
      baumannii and Stenotrophomonas maltophilia (minimum inhibitory concentration = 8
      uM) but appreciably lower haemolytic activity (LC50=185 uM) and cytotoxicity
      against A549 human alveolar basal epithelial cells (LC50=65 uM). The analogue
      shows potential for treatment of nosocomial pulmonary infections caused by
      bacteria that have developed resistance to commonly used antibiotics.

PMID- 22392898
TI  - Midlife blood pressure, amyloid-beta, and risk for Alzheimer disease: one more
      reason to treat hypertension.

PMID- 22392899
TI  - Sildenafil citrate rescues fetal growth in the catechol-O-methyl transferase
      knockout mouse model.
AB  - Preeclampsia and fetal growth restriction are responsible for the majority of
      maternal and perinatal morbidity and mortality associated with complicated
      pregnancies. Although their etiologies are complex and multifactorial, both are
      associated with increased uterine artery resistance. Sildenafil citrate is able
      to rescue the dysfunction observed ex vivo in uterine arteries of women with
      preeclampsia. The ability of sildenafil citrate to increase uterine artery
      vasodilation, thereby decreasing uterine artery resistance and, hence,
      ameliorated preeclampsia and fetal growth restriction, was tested in a mouse
      model of preeclampsia, the catechol-O-methyl transferase knockout mouse (COMT(-/
      )). COMT(-/-) and C57BL/6J mice were treated (0.2 mg/mL in drinking water, n=6
      12) from gestational day 12.5 to 18.5. Measures of pup growth, including body
      weight, crown/rump length, and abdominal circumference, were reduced in COMT(-/-)
      mice; this was normalized after treatment with Sildenafil. COMT(-/-) mice also
      demonstrated abnormal umbilical Doppler waveforms, including reverse arterial
      blood flow velocity. This was normalized after treatment with Sildenafil.
      Abnormal uterine artery Doppler waveforms were not demonstrated in COMT(-/-)
      mice, although ex vivo responses of uterine arteries to phenylephrine were
      increased; moreover, treatment with Sildenafil did improve ex vivo sensitivity to
      an endothelium-dependent vasodilator. The data presented here demonstrate that
      Sildenafil can rescue pup growth and improve abnormal umbilical Doppler
      waveforms, providing support for a potential new therapeutic strategy targeting
      fetal growth restriction.

PMID- 22392900
TI  - The microRNA-328 regulates hypoxic pulmonary hypertension by targeting at insulin
      growth factor 1 receptor and L-type calcium channel-alpha1C.
AB  - Chronic hypoxia is the most common cause of secondary pulmonary hypertension, for
      which the mechanisms are still unclear. Recent studies implicated an important
      role for microRNAs (miRNAs) in hypoxia-mediated responses in various cellular
      processes, including cell apoptosis and proliferation. Therefore, we hypothesized
      that these regulatory molecules might be implicated in the etiology of hypoxic
      pulmonary hypertension. Here we show that miRNA-328, a posttranscriptional
      regulator, was drastically downregulated in the pulmonary artery (PA) after a
      hypoxic assault. PA rings, Western blot, quantitative real-time PCR, in situ
      hybridization, and luciferase assay were used to investigate the role of miRNA
      328 in hypoxic pulmonary hypertension. We found that hypoxia produced a
      significant inhibition of miRNA-328 expression, which was involved in PA
      vasoconstriction and remodeling. Overexpressing miRNA-328 in the transgenic mice
      remarkably decreased the right ventricular systolic pressure and PA wall
      thickness under both normoxia and hypoxia. MiRNA-328 inhibited L-type calcium
      channel-alpha1C expression through a miRNA-328 binding site within the 3'
      untranslational region of L-type calcium channel-alpha1C. The L-type calcium
      channel-alpha1C inhibition attenuated the PA response to KCl. Furthermore, miRNA
      328 suppressed the insulin growth factor 1 receptor, ultimately leading to
      apoptosis of pulmonary arterial smooth muscle cells. The posttranscriptional
      repression of L-type calcium channel-alpha1C and insulin growth factor 1 receptor
      was further confirmed by luciferase reporter assay. These results showed that
      miRNA-328, an important protecting factor, plays a significant role in PA
      constriction and remodeling by regulating multiple gene targets in hypoxic
      pulmonary hypertension.

PMID- 22392901
TI  - Lectin-like oxidized low-density lipoprotein 1 receptor in a reduced
      uteroplacental perfusion pressure rat model of preeclampsia.
AB  - Preeclampsia is a major cause of maternal and fetal morbidity and mortality that
      has been associated with endothelial dysfunction attributed, in part, to
      dyslipidemia, an imbalance in angiogenic factors and oxidative stress. One of the
      many factors that have been shown to be elevated in women with preeclampsia is
      low-density lipoprotein (LDL) and the more oxidizable, small dense LDL, which can
      lead to increased vascular oxidative stress and decreased bioavailability of NO.
      Lectin-like oxidized LDL-1 receptor (LOX-1) is a specific receptor for oxidized
      LDL. We hypothesized that a reduction of placental perfusion using a rat model of
      reduced uteroplacental perfusion pressure would result in enhanced LOX-1
      expression in the maternal vasculature causing impaired vascular endothelial
      function through the actions of increased superoxide production and decreased NO
      mediated vasodilation. We demonstrated a significant increase in the expression
      of the LOX-1 receptor (4.3-fold; P=0.002), endothelial NO synthase (2.7-fold;
      P=0.001), and superoxide (P=0.02) in thoracic aorta of the reduced uteroplacental
      perfusion pressure model, whereas maximal vasodilator function was modestly
      decreased (P<0.05). Endothelial-dependent vasodilator function was unaffected by
      either oxidized LDL or an LOX-1 receptor inhibitor in controls but was modestly
      increased in the presence of both oxidized LDL and the LOX-1 receptor inhibitor
      in reduced uteroplacental perfusion pressure (P=0.03). In summary, we have shown
      that, in a rat model of preeclampsia, there is a dramatic increase in the
      expression levels of both the LOX-1 receptor and the endothelial NO synthase
      enzyme, along with evidence of increased superoxide production and subsequent
      modestly decreased endothelial function.

PMID- 22392902
TI  - Midlife blood pressure, plasma beta-amyloid, and the risk for Alzheimer disease:
      the Honolulu Asia Aging Study.
AB  - beta-Amyloid (Abeta), a vasoactive protein, and elevated blood pressure (BP)
      levels are associated with Alzheimer disease (AD) and possibly vascular dementia.
      We investigated the joint association of midlife BP and Abeta peptide levels with
      the risk for late-life AD and vascular dementia. Subjects were 667 Japanese
      American men (including 73 with a brain autopsy), from the prospective Honolulu
      Heart Program/Honolulu Asia Aging Study (1965-2000). Midlife BP was measured
      starting in 1971 in participants with a mean age of 58 years; Abeta was measured
      in specimens collected in 1980-1982, and assessment of dementia and autopsy
      collection started in 1991-1993. The outcome measures were prevalent (present in
      1991-1993) and incident AD (n=53, including 38 with no contributing
      cardiovascular disease) and vascular dementia (n=24). Cerebral amyloid
      angiopathy, beta-amyloid neuritic plaques, and neurofibrillary tangles were
      evaluated in postmortem tissue. The risk for AD significantly increased with
      lower levels of plasma Abeta (Abeta1-40 hazard ratio: 2.1 [95% CI: 1.4 to 3.1];
      Abeta1-42 hazard ratio: 1.6 [95% CI: 1.1 to 2.3]). Evidence of interaction
      between diastolic BP and plasma Abeta (1-40 P(interaction)<0.05; 1-42
      P(interaction)<0.07) levels indicated that the Abeta-related risk for AD was
      higher when BP was higher. Low plasma Abeta was associated with the presence of
      cerebral amyloid angiopathy (P(trend)<0.05) but not the other neuropathologies.
      Abeta plasma levels start decreasing >=15 years before AD is diagnosed, and the
      association of Abeta to AD is modulated by midlife diastolic BP. Elevated BP may
      compromise vascular integrity leading to cerebral amyloid angiopathy and impaired
      Abeta clearance from the brain.

PMID- 22392903
TI  - Hepatocyte growth factor reduces cardiac fibrosis by inhibiting endothelial
      mesenchymal transition.
AB  - The purpose of this study was to investigate the effect of hepatocyte growth
      factor (HGF) on the pathogenesis of cardiac fibrosis induced by pressure overload
      in mice. Although cardiac fibrosis is attributed to excess pathological
      deposition of extracellular matrix components, the mechanism remains unclear.
      Recent reports revealed that alpha-smooth muscle actin-expressing myofibroblasts
      are primarily responsible for fibrosis. It is believed that myofibroblasts are
      differentiated from resident fibroblasts, whereas the transformation of vascular
      endothelial cells into myofibroblasts, known as endothelial-mesenchymal
      transition, has been suggested to be intimately associated with perivascular
      fibrosis. Thus, we hypothesized that HGF prevents cardiac fibrosis by blocking
      these pathways. We analyzed the pressure-overloaded HGF-transgenic mouse model
      made by transverse aortic constriction. Human coronary artery endothelial cells
      and human cardiac fibroblasts were examined in vitro after being treated with
      transforming growth factor-beta1 or angiotensin II with or without HGF. The
      amount of cardiac fibrosis significantly decreased in pressure-overloaded HGF
      transgenic mice compared with pressure-overloaded nontransgenic controls,
      particularly in the perivascular region. This was accompanied by a reduction in
      the expression levels of fibrosis-related genes and by significant preservation
      of echocardiographic measurements of cardiac function in the HGF-transgenic mice
      (P<0.05). The survival rate 2 months after transverse aortic constriction was
      higher by 45% (P<0.05). HGF inhibited the differentiation of human coronary
      artery endothelial cells into myofibroblasts induced by transforming growth
      factor-beta1 and the phenotypic conversion of human cardiac fibroblasts into
      myofibroblasts. We conclude that HGF reduced cardiac fibrosis by inhibiting
      endothelial-mesenchymal transition and the transformation of fibroblasts into
      myofibroblasts.

PMID- 22392904
TI  - Microdialysis of prostaglandins, thromboxane, and other eicosanoids: recall past
      knowledge.

PMID- 22392905
TI  - Theoretical insights into chirality-controlled SWCNT growth from a
      cycloparaphenylene template.
AB  - A self-assembly mechanism for low-temperature SWCNT growth from a
      [6]cycloparaphenylene ([6]CPP) precursor via ethynyl (C(2)H) radical addition is
      presented, based on non-equilibrium quantum chemical molecular dynamics (QM/MD)
      simulations and density functional theory (DFT) calculations. This mechanism,
      which maintains the (6,6) armchair chirality of a SWCNT fragment throughout the
      growth process, is energetically more favorable than a previously proposed Diels
      Alder-based growth mechanisms [E. H. Fort, et al., J. Mater. Chem. 2011, 21,
      1373]. QM/MD simulations and DFT calculations show that C(2)H radicals play dual
      roles during SWCNT growth, by abstracting hydrogen from the SWCNT fragment and
      providing the carbon source necessary for growth itself. Simulations demonstrate
      that chirality-controlled SWCNT growth from macrocyclic hydrocarbon seed
      molecules with pre-selected edge structure can be accomplished when the reaction
      conditions are carefully selected for hydrogen abstraction by radical species
      during the growth process.

PMID- 22392906
TI  - The high-mobility group A1-estrogen receptor beta nuclear interaction is impaired
      in human testicular seminomas.
AB  - It is well established that estrogens participate in the control of normal
      spermatogenesis and endogenous or environmental estrogens are involved in
      pathological germ cell proliferation including testicular germ cell tumors. The
      effects of estrogen are now known to be mediated by estrogen receptor-alpha
      (ERalpha) and ERbeta subtypes, but only ERbeta has been found in human germ cells
      of normal testis. However, its expression was markedly diminished in human
      testicular seminomas. The expression and the possible interaction of ERbeta and
      HMGA1 were studied in normal germ cells and in human testicular seminomas. GC1
      and TCam-2 germ cell lines, were used; in addition, a tissue micro-array (TMA)
      was built using the most representative areas from 35 cases of human testicular
      seminomas. The expression and the interaction of ERbeta and HMGA1 were observed
      by using immunoprecipitation and Western blot analyses in combination with
      immunocytochemistry and immunofluorescence analyses. Here, we show that ERbeta
      interacts with HMGA1 in normal germ cells, while down regulation of ERbeta
      associates with transcriptional co-regulator HMGA1 over-expression and
      cytoplasmic localization both in human testicular seminomas and in TCam-2 cell
      line. In addition, we show that 17beta-oestradiol induces an HMGA1 increased
      cytoplasmic expression associated to an ERbeta down-regulation in TCam-2 cell
      line. Taken together, our results suggest that exposure to estrogens or estrogen
      mimics, in some as of yet undefined manner, diminishes the ERbeta-mediated growth
      restraint in human testicular seminoma, probably due to the HMGA1 cytoplasmic
      delocalization associated with ERbeta down-regulation.

PMID- 22392907
TI  - The role of nucleotides in the immune and gastrointestinal systems: potential
      clinical applications.
AB  - Nucleotides are low molecular weight biological molecules key to biochemical
      processes. Sources include de novo synthesis, recovery via salvage mechanisms,
      and dietary intakes. Although endogenous production serves as the main nucleotide
      source, evidence suggests that exogenous sources are essential to immune
      competence, intestinal development, and recovery. Dietary nucleotides serve a
      marked role in rapidly proliferating cells where they are necessary for optimal
      function. Accordingly, dietary nucleotides are deemed conditionally essential in
      the presence of various physiological stresses, including growth and development,
      recovery from injury, infection, and certain disease states. Clinical studies
      that evaluated nutrition formulations of nucleotides in combination with other
      specific nutrient substances demonstrated improved clinical outcomes in patients
      characterized as critically ill, injured, immune suppressed, or with chronic
      gastrointestinal conditions. However, conclusions regarding specific benefits of
      nucleotides are limited. Scientific substantiation of nucleotide supplementation
      in infant formula has been reported to improve the maturation and development of
      the intestinal tract as well as immune function. All medical nutrition products
      except for one immune-modulating formulation are devoid of nucleotides. In an
      effort to build on this, the current review presents the data to support
      potential clinical applications for nucleotides in enteral nutrition that may
      contribute to improved outcomes in physiologically stressed patients.

PMID- 22392908
TI  - Standards of practice for nutrition support physicians.

PMID- 22392909
TI  - Establishment of keratinocyte colonies from small-sized cervical intraepithelial
      neoplasia specimens.
AB  - The size of human cervical intraepithelial neoplasia (CIN) biopsies is usually
      very small and standard methods do not allow an adequate number of keratinocytes
      to be isolated for culturing purposes. In this study, a new approach to establish
      keratinocyte cultures from small CIN a tissue fragments was developed. Neoplastic
      specimens and corresponding normal tissues, which were used as controls, were
      digested with collagenase. Tissue-derived fibroblasts and keratinocytes were co
      cultured in calcium and serum medium. Single keratinocyte colonies from primary
      cultures were expanded using a culture medium optimized in our laboratory.
      Primary keratinocyte colonies, as well as expanded colonies, were tested for
      epithelial and cervical markers such as 5, 14, 17, and 19 keratins, and p63 by
      immunofluorescence. Our results indicate that a variable number of primary
      keratinocyte colonies could be detected in neoplastic cultures, depending on the
      grade of cervical lesions from which the colonies originated. Single colonies,
      when cultured with our new medium, grew at a high rate with uniform size and
      morphology for some passages. Epithelial and p63 markers were expressed in
      keratinocyte colonies, as well as in expanded colonies. In conclusion, our study
      reports a rapid and easy culturing system which enables keratinocyte colonies
      from minute cervical tumor tissues to be obtained. Moreover, using the new
      culture medium, keratinocyte colonies can be expanded at a high proliferative
      rate.

PMID- 22392910
TI  - Pharmacokinetics and antitumor efficacy of XMT-1001, a novel, polymeric
      topoisomerase I inhibitor, in mice bearing HT-29 human colon carcinoma
      xenografts.
AB  - PURPOSE: To evaluate the pharmacokinetics and tissue disposition of
      macromolecular camptothecin (CPT) drug conjugate, XMT-1001, and irinotecan (CPT
      11) in mice bearing HT-29 xenograft tumors. EXPERIMENTAL DESIGN: The antitumor
      efficacy of XMT-1001 was evaluated in the mouse HT-29 human colon carcinoma
      xenograft model. XMT-1001 was administered intravenously to female athymic nude
      (nu/nu) mice bearing established HT-29 xenograft tumors (n = 10) at 15, 30, and
      60 mg CPT equivalents/kg on weekly or biweekly schedules. The tumor growth
      inhibition and tumor growth delay endpoints were used for efficacy evaluation. In
      the pharmacokinetic study, XMT-1001 was administered intravenously at a
      pharmacologically relevant dose of 60 mg CPT equivalents/kg * 1 via tail vein or
      an equimolar dose of CPT-11 at 100 mg/kg i.p. * 1. Mice (n = 3 per time point)
      were euthanized from 0.083 to 336 hours after XMT-1001 administration and from
      0.083 to 24 hours after CPT-11. Plasma, tumor, and tissues were collected from
      all animals. A liquid chromatography-tandem mass spectrometry assay was used to
      measure XMT-1001, conjugate release products, CPT-20-O-(N-succinimido-glycinate;
      CPT-SI) and CPT-20-O-(N-succinamidoyl-glycinate; CPT-SA), and CPT. RESULTS: After
      XMT-1001 administration, the majority of the plasma exposure is accounted for by
      conjugated CPT. XMT-1001 exhibited a prolonged exposure of conjugated drug,
      active conjugate primary release products, CPT-SI and CPT-SA, and active CPT,
      which was associated with greater antitumor response compared with CPT-11.
      CONCLUSIONS: XMT-1001 provides an extended systemic and tumor exposure of
      conjugated drug and shows improved antitumor effect compared with CPT-11.

PMID- 22392911
TI  - Inhibition of MEK and PI3K/mTOR suppresses tumor growth but does not cause tumor
      regression in patient-derived xenografts of RAS-mutant colorectal carcinomas.
AB  - PURPOSE: Gene mutations along the Ras pathway (KRAS, NRAS, BRAF, PIK3CA) occur in
      approximately 50% of colorectal cancers (CRC) and correlate with poor response to
      anti-EGF receptor (EGFR) therapies. We assessed the effects of mitogen-activated
      protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK) and
      phosphoinositide 3-kinase (PI3K)/mTOR inhibitors, which neutralize the major Ras
      effectors, in patient-derived xenografts from RAS/RAF/PIK3CA-mutant metastatic
      CRCs (mCRC). EXPERIMENTAL DESIGN: Forty mCRC specimens harboring KRAS, NRAS,
      BRAF, and/or PIK3CA mutations were implanted in nonobese diabetic/severe combined
      immunodeficient (NOD/SCID) mice. Each xenograft was expanded into four treatment
      arms: placebo, the MEK inhibitor AZD6244, the PI3K/mTOR inhibitor, BEZ235, or
      AZD6244 + BEZ235. Cases initially treated with placebo crossed over to AZD6244,
      BEZ235, and the anti-EGFR monoclonal antibody cetuximab. RESULTS: At the 3-week
      evaluation time point, cotreatment of established tumors with AZD6244 + BEZ235
      induced disease stabilization in the majority of cases (70%) but did not lead to
      overt tumor regression. Monotherapy was less effective, with BEZ235 displaying
      higher activity than AZD6244 (disease control rates, DCRs: AZD6244, 27.5%;
      BEZ235, 42.5%). Triple therapy with cetuximab provided further advantage (DCR,
      88%). The extent of disease control declined at the 6-week evaluation time point
      (DCRs: AZD6244, 13.9%; BEZ235, 16.2%; AZD6244 + BEZ235, 34%). Cross-analysis of
      mice harboring xenografts from the same original tumor and treated with each of
      the different modalities revealed subgroups with preferential sensitivity to
      AZD6244 (12.5%), BEZ235 (35%), or AZD6244 + BEZ235 (42.5%); another subgroup
      (10%) showed equivalent response to any treatment. CONCLUSIONS: The prevalent
      growth-suppressive effects produced by MEK and PI3K/mTOR inhibition suggest that
      this strategy may retard disease progression in patients. However, data offer
      cautionary evidence against the occurrence of durable responses.

PMID- 22392912
TI  - Whole blood stem cell reinfusion and escalated dose melphalan in castration
      resistant prostate cancer: a phase 1 study.
AB  - PURPOSE: Nontaxane-based chemotherapeutic options in castrate-resistant prostate
      cancer (CRPC) are limited despite the long natural history of the disease. We
      carried out a phase 1 dose-escalation study of the alkylating agent melphalan
      with autologous stem cell transplantation, comparing rapid changes in circulating
      tumor cells (CTC) and prostate-specific antigen (PSA) as a measure of response.
      EXPERIMENTAL DESIGN: Cohorts of individuals with advanced CRPC received high-dose
      intravenous melphalan, and autologous blood was returned to patients during
      treatment. The efficacy endpoints were the PSA reduction rate, CTC response,
      survival parameters, toxicity and whether reinduction of endocrine sensitivity
      occurred. RESULTS: Twenty-four patients were recruited. Dose escalation was
      feasible with the highest dose cohort being reached. Of 23 individuals evaluable
      for response, 16 had a PSA response of more than 30%; of 11 patients with soft
      tissue disease, 4 achieved a partial response and 7 had stable disease. Patients
      with CTC counts that decreased to less than 5 within 2 weeks from the start of
      therapy had a longer overall survival (30.6 months vs. 15.3 months, P = 0.03)
      Treatment was associated with myelosuppression and frequent hospitalizations. In
      20 patients after the study, hormone therapy was reintroduced when PSA increased
      again; response rates were high. CONCLUSIONS: Autologous transplantation
      following high-dose alkylating agent chemotherapy induces responses but proved
      toxic, although dose escalation proved possible. The possibility of using CTCs to
      identify responders at two weeks may be used to justify such an intensive
      approach. Many individuals went on to further respond to both docetaxel and
      hormonal therapy.

PMID- 22392913
TI  - Improved efficacy of dendritic cell-based immunotherapy by cutaneous laser
      illumination.
AB  - PURPOSE: The present study investigates a convenient laser-based approach to
      enhance dendritic cell (DC) migration and improve DC-based immunotherapy in
      murine models. EXPERIMENTAL DESIGN: Influence of laser illumination on dermal
      tissue microenvironment and migration of DCs following intradermal injection were
      determined by whole-mount immunohistochemistry, transmission electron microscope,
      and flow cytometry. We also investigated in vivo expansion of CTLs by flow
      cytometry, CTL activity by in vitro CTL assay, and antitumor efficacy of DC
      immunization following cutaneous laser illumination in both preventive and
      therapeutic tumor models. RESULTS: Laser illumination was found to significantly
      enlarge perforations in the perilymphatic basement membrane, disarray collagen
      fibers, and disrupt cell-matrix interactions in the dermis. The altered dermal
      tissue microenvironment permitted more efficient migration of intradermally
      injected DCs from the dermis to the draining lymph nodes (dLN). Laser
      illumination also slightly but significantly enhanced the expression of
      costimulatory molecule CD80 and MHC I on inoculated DCs. As a result, more
      vigorous expansion of tumor-specific IFN-gamma(+)CD8(+) T lymphocytes and
      enhanced CTL activity against 4T1 but not irrelevant tumor cells were obtained in
      the laser-treated group over the control group. Laser-augmented DC immunization
      also completely abrogated early growth of 4T1 tumor and B16F10 melanoma in
      preventive tumor models and significantly extended the survival of 4T1-resected
      mice in a therapeutic tumor model. CONCLUSION: These data suggest a simple, safe,
      laser-based approach to significantly enhance DC-based immunotherapy.

PMID- 22392914
TI  - Peptides mimicking the unique ARTS-XIAP binding site promote apoptotic cell death
      in cultured cancer cells.
AB  - PURPOSE: XIAP [X-linked inhibitor of apoptosis (IAP) protein] is the best
      characterized mammalian caspase inhibitor. XIAP is frequently overexpressed in a
      variety of human tumors, and genetic inactivation of XIAP in mice protects
      against lymphoma. Therefore, XIAP is an attractive target for anticancer therapy.
      IAP antagonists based on a conserved IAP-binding motif (IBM), often referred to
      as "Smac-mimetics," are currently being evaluated for cancer therapy in the
      clinic. ARTS (Sept4_i2) is a mitochondrial proapoptotic protein which promotes
      apoptosis by directly binding and inhibiting XIAP via a mechanism that is
      distinct from all other known IAP antagonists. Here, we investigated the ability
      of peptides derived from ARTS to antagonize XIAP and promote apoptosis in cancer
      cell lines. EXPERIMENTAL DESIGN: The ability of synthetic peptides, derived from
      the C-terminus of ARTS, to bind to XIAP, stimulate XIAP degradation, and induce
      apoptosis was examined. We compared the response of several cancer cell lines to
      different ARTS-derived peptides. Pull-down assays were used to examine binding to
      XIAP, and apoptosis was evaluated using terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling, caspase activation, and Western blot analyses of
      caspase substrates. RESULTS: The C-terminus of ARTS contains a unique sequence,
      termed ARTS-IBM (AIBM), which is important for binding to XIAP and cell killing.
      AIBM peptides can bind to XIAP-BIR3, penetrate cancer cells, reduce XIAP levels,
      and promote apoptosis. CONCLUSIONS: Short synthetic peptides derived from the C
      terminus of ARTS are sufficient for binding to XIAP and can induce apoptosis in
      cancer cells. These results provide proof-of-concept for the feasibility of
      developing ARTS-based anticancer therapeutics.

PMID- 22392915
TI  - The HDAC inhibitor LBH589 enhances the antimyeloma effects of the IGF-1RTK
      inhibitor picropodophyllin.
AB  - PURPOSE: We have previously shown the use of the insulin-like growth factor type
      1 receptor tyrosine kinase (IGF-1RTK) inhibitor picropodophyllin (PPP) as an
      attractive strategy to combat multiple myeloma (MM) in vitro and in vivo. After a
      combinatorial drug screening, the histone deacetylase inhibitor LBH589 was shown
      to act in synergy with PPP reducing survival of MM cells. In this study, we tried
      to elucidate the molecular mechanisms underlying this combinatorial effect.
      EXPERIMENTAL DESIGN: The in vitro anti-MM effects of PPP and LBH589 alone and in
      combination were evaluated by studying apoptosis, cell cycle distribution, and
      downstream transcriptome using both human MM cell lines and cells from the murine
      5T3MM model. In vivo the effect on survival of 5T33MM-inoculated mice was
      evaluated. RESULTS: In the human MM cell line RPMI8226, treatment with PPP and
      LBH589 in combination resulted in a five-fold increase of apoptosis, and an
      additive effect on the cleavage of the active forms of caspase-8 was observed as
      compared with the single drug treatments. Cell cycle analysis revealed an
      accumulation of cells in the G(2)-M phase and subsequent downregulation of cell
      cycle regulating proteins. These data were also confirmed in the 5T33MM cells in
      vitro. Also, the transcriptome was analyzed by Affymetrix arrays showing gene
      expression alterations mainly in categories of genes regulating apoptosis and
      cell adhesion. Combined treatment in vivo resulted in a significantly prolonged
      survival of 5T33MM-inoculated mice. CONCLUSIONS: The results indicate an improved
      MM treatment opportunity in using a combination of PPP and LBH589.

PMID- 22392916
TI  - Double down for a double win.
AB  - The rationale for using multiple inhibitors between and within the
      phosphoinositide 3-kinase/AKT/mTOR and RAS/MEK/ERK pathways is scientifically
      compelling, and a limited number of experimental agents are currently being
      tested in phase I combinations. Patient subpopulations, whose tumors are defined
      by genetic lesions, are showing promising responses to this approach.

PMID- 22392918
TI  - Optimization, in vitro-in vivo evaluation, and short-term tolerability of novel
      levofloxacin-loaded PLGA nanoparticle formulation.
AB  - A novel poly(lactic-co-glycolic acid) (PLGA)-based nanoformulation of
      levofloxacin was developed for multidrug-resistant tuberculosis with the purpose
      of achieving sustained release in plasma. After lyophilization of levofloxacin
      loaded nanoparticles, the average size, charge, and polydispersity index were 268
      +/- 18 nm, -10.2 +/- 1.5 mV, and 0.15 +/- 0.03, respectively. The maximum drug
      encapsulation efficiency and loading capacity were 36.9 +/- 6.1% (w/w) and 7.2 +/
      1.2 mg/100 mg nanopowder, respectively. Biphasic extended-release profile was
      produced in vitro. Scanning electron microscopy and Fourier transform infrared
      studies showed spherical shape of drug-loaded nanoparticles and no drug-polymer
      interactions were observed. After single oral administration in mice,
      levofloxacin-loaded PLGA nanoparticles produced sustained release of levofloxacin
      for 4 days in plasma against 24 h for free levofloxacin. Levofloxacin was
      detected in organs (lung, liver, and spleen) for up to 4-6 days in case of
      levofloxacin-loaded nanoparticles, whereas free levofloxacin was cleared within
      24 h. This novel formulation did not show any significant adverse effects on body
      weight and clinical signs in mice. No treatment-related changes were found in
      hematological and biochemical parameters and on histopathological evaluation.
      These results indicate the feasibility of development of an orally efficacious
      safe formulation of levofloxacin with sustained-release properties.

PMID- 22392919
TI  - Behavioural assays based on spontaneous nociceptive responses--a step in the
      right direction: commentary on a paper by Chang Zhu et al. (2012, this issue).

PMID- 22392917
TI  - Molecular and pharmacological evidence for a facilitatory functional role of pre
      synaptic GLUK2/3 kainate receptors on GABA release in rat trigeminal caudal
      nucleus.
AB  - BACKGROUND: Gamma-aminobutyric acid (GABA) and glutamate (GLU) are involved in
      nociceptive signals processing in the trigeminal system. In this study, we
      investigated the influence of excitatory transmission on GABA release in nerve
      terminals isolated from the rat trigeminal caudal nucleus (TCN). METHODS: We
      utilize biochemical (superfused synaptosomes loaded with [(3) H]GABA) and
      morphological (immunofluorescence experiments with specific antibody) techniques.
      RESULTS: Our results show that GLU potentiates the release of [(3) H]GABA evoked
      by 9, 15 and 30 mM [K(+)](e); 15 mM [K(+)](e)-evoked [(3) H]GABA release was also
      reinforced by domoate and kainate (KA), two naturally occurring GLU-receptor
      agonists. The enhancement of 15 mM [K(+)](e)-evoked [(3) H]GABA release produced
      by 100 MUM KA was abolished by NBQX, a mixed AMPA/KA receptor antagonist, but was
      not affected by GYKI52466, a selective AMPA receptor antagonist. ATPA, a
      selective agonist for KA receptors containing the GLUK1 subunit, had no effect on
      depolarization-induced [(3) H]GABA release, and UBP310, which selectively
      antagonizes these same receptors, failed to reverse the KA-induced potentiation
      of 15 mM [K(+)](e)-evoked [(3) H]GABA release. The KA-induced potentiation was
      also unaffected by concanavalin A (10 MUM), a positive allosteric modulator of
      GLUK1- and GLUK2-containing KA receptors. Immunofluorescence experiments revealed
      that GABAergic nerve terminals in the TCN differentially expressed GLUK subunits,
      with GLUK2/3-positive terminals being twice more abundant than GLUK1-containing
      synaptosomes. CONCLUSIONS: These findings indicate that pre-synaptic KA receptors
      facilitating GABA release from TCN nerve terminals mainly express GLUK2/GLUK3
      subunits, supporting the notion that different types of KA receptors are involved
      in the various stages of pain transmission.

PMID- 22392920
TI  - Short- and long-term control of Vespula pensylvanica in Hawaii by fipronil
      baiting.
AB  - BACKGROUND: The invasive western yellowjacket wasp, Vespula pensylvanica
      (Saussure), has significantly impacted the ecological integrity and human welfare
      of Hawaii. The goals of the present study were (1) to evaluate the immediate and
      long-term efficacy of a 0.1% fipronil chicken bait on V. pensylvanica populations
      in Hawaii Volcanoes National Park, (2) to quantify gains in efficacy using the
      attractant heptyl butyrate in the bait stations and (3) to measure the benefits
      of this approach for minimizing non-target impacts to other arthropods. RESULTS:
      The 0.1% fipronil chicken bait reduced the abundance of V. pensylvanica by 95 +/-
      1.2% during the 3 months following treatment and maintained a population
      reduction of 60.9 +/- 3.1% a year after treatment in the fipronil-treated sites
      when compared with chicken-only sites. The addition of heptyl butyrate to the
      bait stations significantly increased V. pensylvanica forager visitation and bait
      take and significantly reduced the non-target impacts of fipronil baiting.
      CONCLUSION: In this study, 0.1% fipronil chicken bait with the addition of heptyl
      butyrate was found to be an extremely effective large-scale management strategy
      and provided the first evidence of a wasp suppression program impacting Vepsula
      populations a year after treatment.

PMID- 22392921
TI  - Cervical lymph node metastasis and papillary thyroid carcinoma: does the
      compartment involved affect survival? Experience from the SEER database.
AB  - PURPOSE: Determine how the location of cervical lymph node metastases affects
      survival in papillary thyroid carcinoma (PTC) patients. METHODS: The
      Surveillance, Epidemiology, and End Results (SEER) database was queried for
      patients diagnosed with PTC. Disease specific survival (DSS) was estimated
      according to node status and extent of cervical involvement by Kaplan-Meier
      analysis. Hazard ratios with 95% confidence intervals to estimate the risk of
      death were calculated using Cox multivariable regression analysis. RESULTS: We
      identified 11,453 PTC cases in the SEER database with complete data describing
      the absence or location of positive nodes. Of these, 40.1% were node-positive;
      56.6%, 34.1%, and 9.3% of node-positive patients had metastasis to the central,
      lateral, and mediastinal compartments, respectively. DSS was worse for node
      positive patients age >= 45 with lateral/mediastinal involvement relative to
      those with central metastasis (P<0.001). Node metastasis did not significantly
      affect survival for patients age <45, regardless of location. CONCLUSIONS:
      Patients age >= 45 with lateral/mediastinal cervical involvement have an
      increased risk of death from PTC in the initial years after diagnosis. Future
      studies are needed to elucidate optimal treatment and surveillance protocols for
      these patients, and also to ascertain the effect of cervical node location on
      long-term survival and disease-recurrence.

PMID- 22392923
TI  - 'I am absolutely shattered': the impact of chronic low back pain on Australian
      Aboriginal people.
AB  - BACKGROUND: Aboriginal people in Australia have been uniquely identified as less
      susceptible to chronic low back pain (CLBP) disability when compared to non
      Aboriginal populations, reportedly due to cultural beliefs about pain. A
      qualitative, culturally secure research approach was used to explore this
      assumption. METHODS: In-depth interviews were undertaken with 32 Aboriginal men
      and women with CLBP in regional and remote areas of Western Australia. Interviews
      were conducted collaboratively with male and female Aboriginal co-investigators,
      and with the support of local Aboriginal community organizations. A primary focus
      was to investigate the impact of CLBP from the perspective of Aboriginal people
      living with the condition. RESULTS: The experience of CLBP was found to be
      multidimensional, impacting on activities of daily life, employment, sport and
      family participation, emotional and cultural well-being. CONCLUSIONS: Contrary to
      previous assumptions, CLBP is profoundly disabling for some Aboriginal people and
      a priority health concern. Issues of gender, cultural obligations and the
      emotional consequences of CLBP are important consideration for health care. These
      findings, and the contextual approach used to gain an in-depth understanding of
      CLBP, may be relevant to populations elsewhere.

PMID- 22392924
TI  - A complete set of self-consistent charge density-functional tight-binding
      parametrization of zinc chalcogenides (ZnX; X=O, S, Se, and Te).
AB  - We have developed a complete set of self-consistent charge density-functional
      tight-binding parameters for Zn?X (X = Zn, O, S, Se, Te, Cd, H, C, and N). The
      transferability of the derived parameters has been tested against Pseudo
      Potential-Perdew, Burke and Ernzerhof (PP-PBE) calculations and experimental
      values (whenever available) for corresponding bulk systems (e.g., hexagonal close
      packing, zinc-blende, and wurtzite(wz)), various kinds of nanostructures (such as
      nanowires, surfaces, and nanoclusters), and also some small molecular systems.
      Our results show that the derived parameters reproduce the structural and
      energetic properties of the above-mentioned systems very well. With the derived
      parameter set, one can study zinc-chalcogenide nanostructures of relatively large
      size which was otherwise prohibited by other methods. The Zn-Cd parametrization
      developed in this article will help in studying large semiconductor hetero
      nanostructures of Zn and Cd chalcogenides such as ZnX/CdX core/shell
      nanoparticles, nanotubes, nanowires, and nanoalloys.

PMID- 22392926
TI  - Susceptibility of inbred mice to Rickettsia parkeri.
AB  - Rickettsia parkeri, a member of the spotted fever group Rickettsia, is the
      causative agent of American boutonneuse fever in humans. Despite the increased
      recognition of human cases, limited information is available regarding the
      infection of invertebrate and vertebrate hosts for this emerging tick-borne
      disease. Toward the development of a viable transmission model and to further
      characterize the pathology associated with R. parkeri infection, inbred mouse
      strains (A/J, BALB/c, C3H/HeJ, and C3H/HeN) were intravenously and intradermally
      inoculated with 10(5) low-passage-number R. parkeri (Portsmouth strain), and
      infection, gross pathology, and histopathology were scored. Additionally, a
      quantitative real-time PCR (qPCR) was performed to estimate rickettsial load in
      heart, lung, spleen, and liver tissues of infected mice at 19 days
      postinoculation. Of the A/J, BALB/c, and C3H/HeN mice, none displayed universal
      pathology consistent with sustained infection. Compared to age-matched control
      mice, the intravenously inoculated C3H/HeJ mice exhibited marked facial edema and
      marked splenomegaly upon gross examination, while the intradermally inoculated
      mice developed characteristic eschar-like lesions. The C3H/HeJ mice also
      exhibited the greatest concentrations of rickettsial DNA from heart, lung, liver,
      and spleen samples when examined by qPCR. The similarity of the pathology of
      human disease and sustained infection suggests that the C3H/HeJ strain of mice is
      a promising candidate for subsequent experiments to examine the tick
      transmission, dissemination, and pathology of R. parkeri rickettsiosis.

PMID- 22392925
TI  - The Vibrio parahaemolyticus ToxRS regulator is required for stress tolerance and
      colonization in a novel orogastric streptomycin-induced adult murine model.
AB  - Vibrio parahaemolyticus, a marine bacterium, is the causative agent of
      gastroenteritis associated with the consumption of seafood. It contains a
      homologue of the toxRS operon that in V. cholerae is the key regulator of
      virulence gene expression. We examined a nonpolar mutation in toxRS to determine
      the role of these genes in V. parahaemolyticus RIMD2210633, an O3:K6 isolate, and
      showed that compared to the wild type, DeltatoxRS was significantly more
      sensitive to acid, bile salts, and sodium dodecyl sulfate stresses. We
      demonstrated that ToxRS is a positive regulator of ompU expression, and that the
      complementation of DeltatoxRS with ompU restores stress tolerance. Furthermore,
      we showed that ToxRS also regulates type III secretion system genes in chromosome
      I via the regulation of the leuO homologue VP0350. We examined the effect of
      DeltatoxRS in vivo using a new orogastric adult murine model of colonization. We
      demonstrated that streptomycin-treated adult C57BL/6 mice experienced prolonged
      intestinal colonization along the entire intestinal tract by the streptomycin
      resistant V. parahaemolyticus. In contrast, no colonization occurred in non
      streptomycin-treated mice. A competition assay between the DeltatoxRS and wild
      type V. parahaemolyticus strains marked with the beta-galactosidase gene lacZ
      demonstrated that the DeltatoxRS strain was defective in colonization compared to
      the wild-type strain. This defect was rescued by ectopically expressing ompU.
      Thus, the defect in stress tolerance and colonization in DeltatoxRS is solely due
      to OmpU. To our knowledge, the orogastric adult murine model reported here is the
      first showing sustained intestinal colonization by V. parahaemolyticus.

PMID- 22392927
TI  - Surface proteome of "Mycobacterium avium subsp. hominissuis" during the early
      stages of macrophage infection.
AB  - "Mycobacterium avium subsp. hominissuis" is a robust and pervasive environmental
      bacterium that can cause opportunistic infections in humans. The bacterium
      overcomes the host immune response and is capable of surviving and replicating
      within host macrophages. Little is known about the bacterial mechanisms that
      facilitate these processes, but it can be expected that surface-exposed proteins
      play an important role. In this study, the selective biotinylation of surface
      exposed proteins, streptavidin affinity purification, and shotgun mass
      spectrometry were used to characterize the surface-exposed proteome of M. avium
      subsp. hominissuis. This analysis detected more than 100 proteins exposed at the
      bacterial surface of M. avium subsp. hominissuis. Comparisons of surface-exposed
      proteins between conditions simulating early infection identified several groups
      of proteins whose presence on the bacterial surface was either constitutive or
      appeared to be unique to specific culture conditions. This proteomic profile
      facilitates an improved understanding of M. avium subsp. hominissuis and how it
      establishes infection. Additionally, surface-exposed proteins are excellent
      targets for the host adaptive immune system, and their identification can inform
      the development of novel treatments, diagnostic tools, and vaccines for
      mycobacterial disease.

PMID- 22392929
TI  - Neutrophils mediate maturation and efflux of lung dendritic cells in response to
      Aspergillus fumigatus germ tubes.
AB  - Invasive aspergillosis is a life-threatening complication of neutrophil
      deficiency or dysfunction. Neutropenia has previously been associated with
      enhanced influx of CD11b-expressing conventional dendritic cells to the lungs in
      response to Aspergillus species, but whether neutrophils directly modulate the
      function of dendritic cells in this infection is not known. We hypothesized that,
      in the setting of intrapulmonary challenge with Aspergillus, neutrophils promote
      the maturation and traffic of lung conventional dendritic cells to draining
      mediastinal lymph nodes. We report that neutropenia results in a marked
      accumulation of dendritic cells in the lungs of mice challenged with Aspergillus
      but greatly diminishes their egress to mediastinal lymph nodes independent of
      neutrophil microbicidal functions. Furthermore, the phenotype of lung dendritic
      cells was more immature in neutropenic animals than in nonneutropenic mice
      exposed to the microorganism. Consistent with this, coincubation with neutrophils
      greatly enhanced the upregulation of costimulatory molecules on dendritic cells
      exposed to Aspergillus in vitro, a process that was dependent on cell contact and
      the dendritic cell receptor DC-SIGN. Taken together, our data support an
      immunomodulatory cross talk between neutrophils and dendritic cells in the
      context of host response to Aspergillus that promotes the maturation and efflux
      of lung dendritic cells.

PMID- 22392928
TI  - The streptomycin-treated mouse intestine selects Escherichia coli envZ missense
      mutants that interact with dense and diverse intestinal microbiota.
AB  - Previously, we reported that the streptomycin-treated mouse intestine selected
      nonmotile Escherichia coli MG1655 flhDC deletion mutants of E. coli MG1655 with
      improved colonizing ability that grow 15% faster in vitro in mouse cecal mucus
      and 15 to 30% faster on sugars present in mucus (M. P. Leatham et al., Infect.
      Immun. 73:8039-8049, 2005). Here, we report that the 10 to 20% remaining motile
      E. coli MG1655 are envZ missense mutants that are also better colonizers of the
      mouse intestine than E. coli MG1655. One of the flhDC mutants, E. coli MG1655
      DeltaflhD, and one of the envZ missense mutants, E. coli MG1655 mot-1, were
      studied further. E. coli MG1655 mot-1 is more resistant to bile salts and colicin
      V than E. coli MG1655 DeltaflhD and grows ca. 15% slower in vitro in mouse cecal
      mucus and on several sugars present in mucus compared to E. coli MG1655 DeltaflhD
      but grows 30% faster on galactose. Moreover, E. coli MG1655 mot-1 and E. coli
      MG1655 DeltaflhD appear to colonize equally well in one intestinal niche, but E.
      coli MG1655 mot-1 appears to use galactose to colonize a second, smaller
      intestinal niche either not colonized or colonized poorly by E. coli MG1655
      DeltaflhD. Evidence is also presented that E. coli MG1655 is a minority member of
      mixed bacterial biofilms in the mucus layer of the streptomycin-treated mouse
      intestine. We offer a hypothesis, which we call the "Restaurant" hypothesis, that
      explains how nutrient acquisition in different biofilms comprised of different
      anaerobes can account for our results.

PMID- 22392930
TI  - Plasmodium falciparum line-dependent association of in vitro growth-inhibitory
      activity and risk of malaria.
AB  - Plasmodium falciparum's ability to invade erythrocytes is essential for its
      survival within the human host. Immune mechanisms that impair this ability are
      therefore expected to contribute to immunity against the parasite. Plasma of
      humans who are naturally exposed to malaria has been shown to have growth
      inhibitory activity (GIA) in vitro. However, the importance of GIA in relation to
      protection from malaria has been unclear. In a case-control study nested within a
      longitudinally followed population in Tanzania, plasma samples collected at
      baseline from 171 individuals (55 cases and 116 age-matched controls) were
      assayed for GIA using three P. falciparum lines (3D7, K1, and W2mef) chosen based
      on their erythrocyte invasion phenotypes. Distribution of GIA differed between
      the lines, with most samples inhibiting the growth of 3D7 and K1 and enhancing
      the growth of W2mef. GIA to 3D7 was associated with a reduced risk of malaria
      within 40 weeks of follow-up (odds ratio, 0.45; 95% confidence interval [CI],
      0.21 to 0.96; P = 0.04), whereas GIA to K1 and W2mef was not. These results show
      that GIA, as well as its association with protection from malaria, is dependent
      on the P. falciparum line and can be explained by differences in erythrocyte
      invasion phenotypes between parasite lines. Our study contributes knowledge on
      the biological importance of growth inhibition and the potential influence of P.
      falciparum erythrocyte invasion phenotypic differences on its relationship to
      protective immunity against malaria.

PMID- 22392931
TI  - Development of a contemporary animal model of Candida albicans-associated denture
      stomatitis using a novel intraoral denture system.
AB  - Denture stomatitis (DS) is a fungal infection characterized by inflammation of
      the oral mucosa in direct contact with the denture and affects up to 50% of
      denture wearers. Despite the prevalence, very little is known about the role of
      fungal or host factors that contribute to pathogenesis. Recently, we developed a
      novel intraoral denture system for rodent research. This denture system consists
      of custom-fitted fixed and removable parts to allow repeated sampling and
      longitudinal studies. The purpose of this study was to use this denture system to
      develop a clinically relevant animal model of DS. To establish DS, rats were
      inoculated with pelleted Candida albicans, which resulted in sustained
      colonization of the denture and palate for 8 weeks postinoculation. Biofilm
      formation on the denture was observed by week 4 and on the palate by week 6
      postinoculation. Rats were monitored for clinical signs of disease by assigning a
      clinical score after macroscopic examination of the palate tissue according to
      Newton's method. By week 4 postinoculation, the majority of inoculated rats with
      dentures exhibited a clinical score of 1 (pinpoint erythema). By week 6 and week
      8 postinoculation, increasing percentages of rats exhibited a clinical score of 2
      (diffuse erythema/edema). Histological analysis of palate tissue demonstrated
      progressively increasing inflammatory cell recruitment throughout the time course
      of the infection. Palatal biofilm formation was commensurate with development of
      palatal erythema, which suggests a role for biofilm in the inflammatory response.

PMID- 22392932
TI  - Tetanus toxin and botulinum toxin a utilize unique mechanisms to enter neurons of
      the central nervous system.
AB  - Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the most toxic
      proteins for humans. While BoNTs cause flaccid paralysis, TeNT causes spastic
      paralysis. Characterized BoNT serotypes enter neurons upon binding dual
      receptors, a ganglioside and a neuron-specific protein, either synaptic vesicle
      protein 2 (SV2) or synaptotagmin, while TeNT enters upon binding gangliosides as
      dual receptors. Recently, TeNT was reported to enter central nervous system (CNS)
      neurons upon synaptic vesicle cycling that was mediated by the direct binding to
      SV2, implying that TeNT and BoNT utilize common mechanisms to enter CNS neurons.
      This prompted an assessment of TeNT entry into CNS neurons, using the prototypic
      BoNT serotype A as a reference for SV2-mediated entry into synaptic vesicles,
      analyzing the heavy-chain receptor binding domain (HCR) of each toxin. Synaptic
      vesicle cycling stimulated the entry of HCR/A into neurons, while HCR/T entered
      neurons with similar levels of efficiency in depolarized and nondepolarized
      neurons. ImageJ analysis identified two populations of cell-associated HCR/T in
      synaptic vesicle cycling neurons, a major population which segregated from HCR/A
      and a minor population which colocalized with HCR/A. HCR/T did not inhibit HCR/A
      entry into neurons in competition experiments and did not bind SV2, the protein
      receptor for BoNT/A. Intoxication experiments showed that TeNT efficiently
      cleaved VAMP2 in depolarized neurons and neurons blocked for synaptic vesicle
      cycling. These experiments demonstrate that TeNT enters neurons by two pathways,
      one independent of stimulated synaptic vesicle cycling and one by synaptic
      vesicles independent of SV2, showing that TeNT and BoNT/A enter neurons by unique
      mechanisms.

PMID- 22392934
TI  - The effect of neoadjuvant chemoradiotherapy on airway colonization and
      postoperative respiratory complications in patients undergoing oesophagectomy for
      oesophageal cancer.
AB  - Respiratory complication is one of the important postoperative complications of
      oesophageal cancer. The aim of this study was to evaluate whether neoadjuvant
      chemotherapy before surgery is effective for postoperative respiratory
      complications. In this study, patients with oesophageal cancer were divided into
      two group: one with neoadjuvant therapy and the other without neoadjuvant
      therapy. Before surgery, they all underwent bronchoscopy and bronchoalveolar
      lavage. We evaluated respiratory complications and the effects of preoperative
      neoadjuvant therapy. Forty patients (M/F = 23/17 and mean age 61 years) were
      enrolled in this study. Twenty-two cases had cancer in the middle part and 18 in
      the lower part of the oesophagus. Significant correlation was observed between
      the number of positive micro-organism and difficulty in weaning and receiving
      neoadjuvant therapy. But no significant correlation was found between neoadjuvant
      therapy and respiratory complications.

PMID- 22392935
TI  - Is routine chest radiography indicated following chest drain removal after
      cardiothoracic surgery?
AB  - A best evidence topic was written according to a structured protocol. The
      question addressed was whether routine chest radiography is indicated following
      chest drain removal in patients undergoing cardiothoracic surgery. A total of 356
      papers were found using the reported searches; of which, 6 represented the best
      evidence to answer the clinical question. The authors, date, journal, study type,
      population, main outcome measures and results are tabulated. Reported measures
      were mean duration of drains left in situ, timing of drain removal, pathology
      detected on chest radiographs (CXRs), interventions following imaging and
      clinical assessment, complications in patients not undergoing routine CXRs and
      the cost saving of omitting routine CXRs. One large cohort study reported the
      detection of pathology in 79% of clinically indicated CXRs in comparison to 40%
      of routine CXRs (P = 0.005). Ninety-five per cent of the non-routine CXR cohort
      remained asymptomatic and required no intervention. One large observational study
      reported the detection of new pneumothoraces in 9.3% of patients, 70.3% of which
      were barely perceptible. Intervention following CXR was required in 0.25% and
      only one medium-sized pneumothorax would have been potentially missed without
      CXR. Another large observational study reported intervention following CXR in
      1.9% and the presence of relevant clinical signs and symptoms to be a significant
      predictor of major intervention (P < 0.01). A smaller observational study
      reported no pathology detected or intervention following CXR in 98% and the cost
      saving of omitting a single CXR at L10 000 per annum. Another small observational
      study reported only 7% of CXRs to be clinically indicated with a false-positive
      rate of 100%, and a false-negative rate of 7% in CXRs not clinically indicated.
      The smallest study reported no complications in the non-CXR cohort and only one
      patient undergoing intervention in the routine CXR cohort. We conclude that there
      is evidence that routine post drain removal CXR provides no diagnostic or
      therapeutic advantage over clinically indicated CXR or simple clinical
      assessment. The best evidence studies reported the detection of pathology on
      routine CXR ranging from 2 to 40% compared with 79% in clinically indicated CXRs
      (P = 0.005). Whilst the rate of intervention following routine CXR was as high as
      4% in the smallest study, clinical signs and symptoms suggestive of pathology
      were a significant predictor of major re-intervention (P < 0.01).

PMID- 22392933
TI  - Quorum-sensing and BvrR/BvrS regulation, the type IV secretion system, cyclic
      glucans, and BacA in the virulence of Brucella ovis: similarities to and
      differences from smooth brucellae.
AB  - Brucella ovis is a rough bacterium--lacking O-polysaccharide chains in the
      lipopolysaccharide--that is virulent in its natural host and whose virulence
      mechanisms remain almost unexplored. In a search for additional traits that
      distinguish B. ovis from smooth Brucella, which require O-polysaccharide chains
      for virulence, we have analyzed the significance in B. ovis of the main virulence
      factors described for smooth Brucella. Attempts to obtain strains of virulent B.
      ovis strain PA that are mutated in the BvrR/BvrS two-component regulatory system
      were unsuccessful, suggesting the requirement of that system for in vitro
      survival, while the inactivation of bacA--in contrast to the results seen with
      smooth Brucella--did not affect splenic colonization in mice or behavior in
      J774.A1 murine macrophages. Defects in the synthesis of cyclic beta-1,2 glucans
      reduced the uptake of B. ovis PA in macrophages and, although the intracellular
      multiplication rate was unaffected, led to attenuation in mice. Growth of strains
      with mutations in the type IV secretion system (encoded by the virB operon) and
      the quorum-sensing-related regulator VjbR was severely attenuated in the mouse
      model, and although the mutant strains internalized like the parental strain in
      J774.A1 murine macrophages, they were impaired for intracellular replication. As
      described for B. melitensis, VjbR regulates the transcription of the virB operon
      positively, and the N-dodecanoyl-dl-homoserine lactone (C(12)-HSL) autoinducer
      abrogates this effect. In contrast, no apparent VjbR-mediated regulation of the
      fliF flagellar gene was observed in B. ovis, probably due to the two deletions
      detected upstream of fliF. These results, together with others reported in the
      text, point to similarities between rough virulent B. ovis and smooth Brucella
      species as regards virulence but also reveal distinctive traits that could be
      related to the particular pathogenicity and host tropism characteristics of B.
      ovis.

PMID- 22392936
TI  - Is an intra-oesophageal bougie of use during Nissen fundoplication?
AB  - A best-evidence topic was written according to a structured protocol. The
      question addressed was whether the use of an intra-oesophageal bougie during
      Nissen fundoplication reduces post-operative dysphagia. A total of 34 papers were
      found using the reported searches of which eight represented the best evidence to
      answer the clinical question. The authors, date, journal, study type, population,
      main outcome measures and results are tabulated. The popularity of bougie
      placement is likely to have been encouraged by an early study reported in this
      article in 1986 associating the use of a larger bougie with reduction of
      postoperative dysphagia. A more recent randomized study in 2000 also associated
      the use of bougie with significantly less long-term and severe dysphagia. Four
      retrospective studies showed no advantage from the use of a bougie, and the
      potential benefit are countered by the largest published series in the literature
      reporting the incidence of oesophageal perforation owing to bougie placement at
      0.8%. Despite this risk, a survey of 393 German surgeons in 2005 revealed that
      46% use a bougie. In summary, we conclude that there is some evidence to suggest
      that both the presence and size of bougie may have an impact on dysphagia. The
      evidence is not substantial enough to recommend change in clinical practice and
      its use must be weighed against the risk of oesophageal injury which patients
      should be consented for. These conclusions are in accordance with the 2010
      Guidelines for Surgical Treatment of Gastroesophageal Reflux disease by the
      Society of American Gastrointestinal and Endoscopic Surgeons who give a Grade B
      recommendation for the placement of an oesophageal dilator. It is important that
      future studies are adequately powered and designed to measure longitudinal
      outcomes such as dysphagia severity with validated assessment tools at
      appropriate follow-up points. The measurement and usefulness of health-related
      quality of life needs to be investigated further in this patient population.

PMID- 22392937
TI  - Influence of relative age on diagnosis and treatment of attention
      deficit/hyperactivity disorder in children.
AB  - BACKGROUND: The annual cut-off date of birth for entry to school in British
      Columbia, Canada, is Dec. 31. Thus, children born in December are typically the
      youngest in their grade. We sought to determine the influence of relative age
      within a grade on the diagnosis and pharmacologic treatment of attention
      deficit/hyperactivity disorder (ADHD) in children. METHODS: We conducted a cohort
      study involving 937 943 children in British Columbia who were 6-12 years of age
      at any time between Dec. 1, 1997, and Nov. 30, 2008. We calculated the absolute
      and relative risk of receiving a diagnosis of ADHD and of receiving a
      prescription for a medication used to treat ADHD (i.e., methylphenidate,
      dextroamphetamine, mixed amphetamine salts or atomoxetine) for children born in
      December compared with children born in January. RESULTS: Boys who were born in
      December were 30% more likely (relative risk [RR] 1.30, 95% confidence interval
      [CI] 1.23-1.37) to receive a diagnosis of ADHD than boys born in January. Girls
      born in December were 70% more likely (RR 1.70, 95% CI 1.53-1.88) to receive a
      diagnosis of ADHD than girls born in January. Similarly, boys were 41% more
      likely (RR 1.41, 95% CI 1.33-1.50) and girls 77% more likely (RR 1.77, 95% CI
      1.57-2.00) to be given a prescription for a medication to treat ADHD if they were
      born in December than if they were born in January. INTERPRETATION: The results
      of our analyses show a relative-age effect in the diagnosis and treatment of ADHD
      in children aged 6-12 years in British Columbia. These findings raise concerns
      about the potential harms of overdiagnosis and overprescribing. These harms
      include adverse effects on sleep, appetite and growth, in addition to increased
      risk of cardiovascular events.

PMID- 22392938
TI  - Decisions: does a patient with a thunderclap headache need a lumbar puncture?

PMID- 22392940
TI  - Advocacy groups continue to scorn screening guidelines.

PMID- 22392941
TI  - Health in Colombia: treating the displaced.

PMID- 22392942
TI  - Aboriginal children suffer while governments ignore Jordan's Principle.

PMID- 22392943
TI  - Diffuse panbronchiolitis.

PMID- 22392944
TI  - Health in Colombia: a system in crisis.

PMID- 22392946
TI  - Health in Colombia: the chronic disease burden.

PMID- 22392947
TI  - Informed consent for clinical treatment.

PMID- 22392948
TI  - Popping the genetics bubble.

PMID- 22392949
TI  - Accuracy of single-pass whole-body computed tomography for detection of injuries
      in patients with major blunt trauma.
AB  - BACKGROUND: Contrast-enhanced whole-body computed tomography (also called "pan
      scanning") is considered to be a conclusive diagnostic tool for major trauma. We
      sought to determine the accuracy of this method, focusing on the reliability of
      negative results. METHODS: Between July 2006 and December 2008, a total of 982
      patients with suspected severe injuries underwent single-pass pan-scanning at a
      metropolitan trauma centre. The findings of the scan were independently evaluated
      by two reviewers who analyzed the injuries to five body regions and compared the
      results to a synopsis of hospital charts, subsequent imaging and interventional
      procedures. We calculated the sensitivity and specificity of the pan-scan for
      each body region, and we assessed the residual risk of missed injuries that
      required surgery or critical care. RESULTS: A total of 1756 injuries were
      detected in the 982 patients scanned. Of these, 360 patients had an Injury
      Severity Score greater than 15. The median length of follow-up was 39
      (interquartile range 7-490) days, and 474 patients underwent a definitive
      reference test. The sensitivity of the initial pan-scan was 84.6% for head and
      neck injuries, 79.6% for facial injuries, 86.7% for thoracic injuries, 85.7% for
      abdominal injuries and 86.2% for pelvic injuries. Specificity was 98.9% for head
      and neck injuries, 99.1% for facial injuries, 98.9% for thoracic injuries, 97.5%
      for abdominal injuries and 99.8% for pelvic injuries. In total, 62 patients had
      70 missed injuries, indicating a residual risk of 6.3% (95% confidence interval
      4.9%-8.0%). INTERPRETATION: We found that the positive results of trauma pan
      scans are conclusive but negative results require subsequent confirmation. The
      pan-scan algorithms reduce, but do not eliminate, the risk of missed injuries,
      and they should not replace close monitoring and clinical follow-up of patients
      with major trauma.

PMID- 22392951
TI  - Approach to the male patient with congenital hypogonadotropic hypogonadism.
AB  - The term "congenital hypogonadotropic hypogonadism" (CHH) refers to a group of
      disorders featuring complete or partial pubertal failure due to insufficient
      secretion of the pituitary gonadotropins LH and FSH. Many boys (or their parents)
      will seek medical consultation because of partial or absent virilization after 14
      yr of age. Small testes are very frequent, but height is generally normal.
      Laboratory diagnosis of hypogonadotropic hypogonadism is relatively simple, with
      very low circulating total testosterone and low to low-normal gonadotropin and
      inhibin B levels. This hormone profile rules out a primary testicular disorder.
      Before diagnosing CHH, however, it is necessary to rule out a pituitary tumor or
      pituitary infiltration by imaging studies, juvenile hemochromatosis, and a
      systemic disorder that, by undermining nutritional status, could affect
      gonadotropin secretion and pubertal development. Anterior pituitary function must
      be thoroughly investigated to rule out a more complex endocrine disorder with
      multiple hormone deficiencies and thus to conclude that the hypogonadotropic
      hypogonadism is isolated. The most likely differential diagnosis before age 18 yr
      is constitutional delay of puberty. Apart from non-Kallmann syndromic forms,
      which are often diagnosed during childhood, the two main forms of CHH seen by
      endocrinologists are Kallmann syndrome, in which CHH is associated with impaired
      sense of smell, and isolated CHH with normal olfaction. Anosmia can be easily
      diagnosed by questioning the patient, whereas olfactometry is necessary to
      determine reliably whether olfaction is normal or partially defective. This step
      is important before embarking on a search for genetic mutations, which will also
      be useful for genetic counseling. The choice of a particular hormone replacement
      therapy protocol aimed at virilizing the patient will depend on age at diagnosis
      and local practices.

PMID- 22392950
TI  - Approach to the hypophosphatemic patient.
AB  - Hypophosphatemia is commonly missed due to nonspecific signs and symptoms, but it
      causes considerable morbidity and in some cases contributes to mortality. Three
      primary mechanisms of hypophosphatemia exist: increased renal excretion,
      decreased intestinal absorption, and shifts from the extracellular to
      intracellular compartments. Renal hypophosphatemia can be further divided into
      fibroblast growth factor 23-mediated or non-fibroblast growth factor 23-mediated
      causes. Proper diagnosis requires a thorough medication history, family history,
      physical examination, and assessment of renal tubular phosphate handling to
      identify the cause. During the past decade, our understanding of phosphate
      metabolism has grown greatly through the study of rare disorders of phosphate
      homeostasis. Treatment of hypophosphatemia depends on the underlying disorder and
      requires close biochemical monitoring. This article illustrates an approach to
      the hypophosphatemic patient and discusses normal phosphate metabolism.

PMID- 22392952
TI  - Adipocyte maturation arrest: a determinant of systemic insulin resistance to
      glucose disposal.

PMID- 22392953
TI  - An encore for the repeats: new insights into an old genetic variant.

PMID- 22392955
TI  - Congenital adrenal hyperplasia--more dogma bites the dust.

PMID- 22392954
TI  - Take another CYP: confirming a novel mechanism for "idiopathic" hypercalcemia.

PMID- 22392961
TI  - Type 2 diabetes and insulin secretagogues.

PMID- 22392963
TI  - Back to the drawing board.

PMID- 22392964
TI  - A retrospective observational study on the use of capecitabine in patients with
      severe renal impairment (GFR <30 mL/min) and end stage renal disease on
      hemodialysis.
AB  - Capecitabine (Xeloda) is an orally administered precursor of 5'deoxy-5
      fluorouridine, which is a preferentially activated to 5-fluorouracil in tumors.
      It is used in the treatment of colorectal, gastric, and breast cancers. Based on
      a single Phase II trial, which included a total of 4 patients with severe renal
      impairment (GFR <30 mL/min), the manufacturer issued a 'Dear Doctor' letter
      contraindicating the use of capecitabine in these patients since a high rate of
      grade 3 and 4 adverse events were observed and because these patients tolerated
      shorter treatment durations.(1) We retrospectively studied 12 patients with a GFR
      <30 mL/min, including 2 patients with end stage renal disease on hemodialysis,
      who received capecitabine for mean duration of 7.1 months (1-26 months). The mean
      serum creatinine at the time of initiation of the drug was 2.63 mg/dL (1.8-6.4
      mg/dL) and mean GFR was 20.9 mL/min (8-29 mL/min). Two patients remained on
      capecitabine after they progressed to end stage renal disease (ESRD) requiring
      hemodialysis (HD) for an additional 17 and 6 months, respectively. Most patients
      reported grade 1 and 2 adverse effects (AE), 2 patients reported grade 3 diarrhea
      and one patient died while on treatment with capecitabine. The starting dose
      ranged from 250 to 1000 mg/m(2), given twice daily at variable intervals. Dose
      modifications, with reductions of up to 50% of the starting dose, were made
      following reports of AEs. Serum tumor marker levels and/or follow up imaging
      studies were available on 9 patients. Response to capecitabine was documented in
      4 patients, stable disease in 2, and disease progression in 3. We conclude that,
      with close monitoring of their clinical and chemical data, and with dose
      modification based on reported AEs, capecitabine can be safely administered to
      patients with severe renal impairment, including patients on hemodialysis.

PMID- 22392965
TI  - Mouth care protocol for oral mucositis.

PMID- 22392967
TI  - Transesophageal Doppler measurement of renal arterial blood flow velocities and
      indices in children.
AB  - BACKGROUND: Doppler-derived renal blood flow indices have been used to assess
      renal pathologies. However, transesophageal ultrasonography (TEE) has not been
      previously used to assess these renal variables in pediatric patients. In this
      study, we (a) assessed whether TEE allows adequate visualization of the renal
      parenchyma and renal artery, and (b) evaluated the concordance of TEE Doppler
      derived renal blood flow measurements/indices compared with a standard
      transabdominal renal ultrasound (TAU) in children. METHODS: This prospective
      cohort study enrolled 28 healthy children between the ages of 1 and 17 years
      without known renal dysfunction who were undergoing atrial septal defect device
      closure in the cardiac catheterization laboratory. TEE was used to obtain Doppler
      renal artery blood velocities (peak systolic velocity, end-diastolic velocity,
      mean diastolic velocity, resistive index, and pulsatility index), and these
      values were compared with measurements obtained by TAU. Concordance correlation
      coefficient (CCC) was used to determine clinically significant agreement between
      the 2 methods. The Bland-Altman plots were used to determine whether these 2
      methods agree sufficiently to be used interchangeably. Statistical significance
      was accepted at P <= 0.05. RESULTS: Obtaining 2-dimensional images of kidney
      parenchyma and Doppler-derived measurements using TEE in children is feasible.
      There was statistically significant agreement between the 2 methods for all
      measurements. The CCC between the 2 imaging techniques was 0.91 for the
      pulsatility index and 0.66 for the resistive index. These coefficients were
      sensitive to outliers. When the highest and lowest data points were removed from
      the analysis, the CCC between the 2 imaging techniques was 0.62 for the
      pulsatility index and 0.50 for the resistive index. The 95% confidence interval
      (CI) for pulsatility index was 0.35 to 0.98 and for resistive index was 0.21 to
      0.89. The Bland-Altman plots indicate good agreement between the 2 methods; for
      the pulsatility index, the limits of agreement were -0.80 to 0.53. The
      correlation of the size of the measurement and the mean difference in methods (
      0.14; 95% CI = -0.28, 0.01) was not statistically significant (r = 0.31, P =
      0.17). For the resistive index, the limits of agreement were -0.22 to 0.12. The
      correlation of the size of the measurement and the mean difference in methods (
      0.05; 95% CI = -0.09, -0.01) was not statistically significant (r = 0.10, P =
      0.65). CONCLUSION: This study confirms the feasibility of obtaining 2-dimensional
      images of kidney parenchyma and Doppler-derived measurements using TEE in
      children. Angle-independent TEE Doppler-derived indices show significant
      concordance with those derived by TAU. Further studies are required to assess
      whether this correlation holds true in the presence of renal pathology. This
      technique has the potential to help modulate intraoperative interventions based
      on their impact on renal variables and may prove helpful in the perioperative
      period for children at risk of acute kidney injury.

PMID- 22392968
TI  - Binding site and affinity prediction of general anesthetics to protein targets
      using docking.
AB  - BACKGROUND: The protein targets for general anesthetics remain unclear. A tool to
      predict anesthetic binding for potential binding targets is needed. In this
      study, we explored whether a computational method, AutoDock, could serve as such
      a tool. METHODS: High-resolution crystal data of water-soluble proteins
      (cytochrome C, apoferritin, and human serum albumin), and a membrane protein (a
      pentameric ligand-gated ion channel from Gloeobacter violaceus [GLIC]) were used.
      Isothermal titration calorimetry (ITC) experiments were performed to determine
      anesthetic affinity in solution conditions for apoferritin. Docking calculations
      were performed using DockingServer with the Lamarckian genetic algorithm and the
      Solis and Wets local search method (http://www.dockingserver.com/web). Twenty
      general anesthetics were docked into apoferritin. The predicted binding constants
      were compared with those obtained from ITC experiments for potential
      correlations. In the case of apoferritin, details of the binding site and their
      interactions were compared with recent cocrystallization data. Docking
      calculations for 6 general anesthetics currently used in clinical settings
      (isoflurane, sevoflurane, desflurane, halothane, propofol, and etomidate) with
      known 50% effective concentration (EC(50)) values were also performed in all
      tested proteins. The binding constants derived from docking experiments were
      compared with known EC(50) values and octanol/water partition coefficients for
      the 6 general anesthetics. RESULTS: All 20 general anesthetics docked
      unambiguously into the anesthetic binding site identified in the crystal
      structure of apoferritin. The binding constants for 20 anesthetics obtained from
      the docking calculations correlate significantly with those obtained from ITC
      experiments (P = 0.04). In the case of GLIC, the identified anesthetic binding
      sites in the crystal structure are among the docking predicted binding sites, but
      not the top ranked site. Docking calculations suggest a most probable binding
      site located in the extracellular domain of GLIC. The predicted affinities
      correlated significantly with the known EC(50) values for the 6 frequently used
      anesthetics in GLIC for the site identified in the experimental crystal data (P =
      0.006). However, predicted affinities in apoferritin, human serum albumin, and
      cytochrome C did not correlate with these 6 anesthetics' known experimental
      EC(50) values. A weak correlation between the predicted affinities and the
      octanol/water partition coefficients was observed for the sites in GLIC.
      CONCLUSION: We demonstrated that anesthetic binding sites and relative affinities
      can be predicted using docking calculations in an automatic docking server
      (AutoDock) for both water-soluble and membrane proteins. Correlation of predicted
      affinity and EC(50) for 6 frequently used general anesthetics was only observed
      in GLIC, a member of a protein family relevant to anesthetic mechanism.

PMID- 22392970
TI  - Aromatherapy as treatment for postoperative nausea: a randomized trial.
AB  - BACKGROUND: Postoperative nausea (PON) is a common complication of anesthesia and
      surgery. Antiemetic medication for higher-risk patients may reduce but does not
      reliably prevent PON. We examined aromatherapy as a treatment for patients
      experiencing PON after ambulatory surgery. Our primary hypothesis was that in
      comparison with inhaling a placebo, PON will be reduced significantly by
      aromatherapy with (1) essential oil of ginger, (2) a blend of essential oils of
      ginger, spearmint, peppermint, and cardamom, or (3) isopropyl alcohol. Our
      secondary hypothesis was that the effectiveness of aromatherapy will depend upon
      the agent used. METHODS: A randomized trial of aromatherapy with patients who
      reported nausea in the postanesthesia care unit was conducted at one ambulatory
      surgical center. Eligibility criteria were adult, able to give consent, and no
      history of coagulation problems or allergy to the aromatherapy agents. Before
      surgery, demographic and risk factors were collected. Patients with a nausea
      level of 1 to 3 on a verbal descriptive scale (0-3) received a gauze pad
      saturated with a randomly chosen aromatherapy agent and were told to inhale
      deeply 3 times; nausea (0-3) was then measured again in 5 minutes. Prophylactic
      and postnausea antiemetics were given as ordered by physicians or as requested by
      the patient. RESULTS: A total of 1151 subjects were screened for inclusion; 303
      subjects reporting nausea were enrolled (26.3%), and 301 meeting protocol were
      analyzed (26.2%). The change in nausea level was significant for the blend (P <
      0.001) and ginger (P = 0.002) versus saline but not for alcohol (P < 0.76). The
      number of antiemetic medications requested after aromatherapy was also
      significantly reduced with ginger or blend aromatherapy versus saline (P = 0.002
      and P < 0.001, respectively). CONCLUSION: The hypothesis that aromatherapy would
      be effective as a treatment for PON was supported. On the basis of our results,
      future research further evaluating aromatherapy is warranted. Aromatherapy is
      promising as an inexpensive, noninvasive treatment for PON that can be
      administered and controlled by patients as needed.

PMID- 22392971
TI  - Cyanide toxicity in juvenile pigs and its reversal by a new prodrug, sulfanegen
      sodium.
AB  - BACKGROUND: Cyanide (CN) toxicity is a serious clinical problem and can occur
      with sodium nitroprusside (SNP) administration, accidental smoke inhalation,
      industrial mishaps, and bio-terrorism. In this study, we induced severe CN
      toxicity independently with SNP or sodium cyanide (NaCN) in a juvenile pig model
      to demonstrate reversal of severe CN toxicity with a new antidote, sulfanegen
      sodium, a prodrug of 3-mercaptopyruvate. METHODS: SNP study: A pilot study in 11
      anesthetized, mechanically ventilated juvenile pigs allowed us to determine the
      dose of SNP to induce CN toxicity. Blood CN, serum lactates, and blood gases were
      monitored. CN toxicity was defined as the occurrence of severe lactic acidosis
      accompanied by significant elevation in blood CN levels. Based on this pilot
      study, 8 anesthetized pigs received a high-dose i.v. infusion of SNP (100 mg/h)
      for 2 hours to induce CN toxicity. They were then randomized to receive either
      sulfanegen sodium or placebo. Four pigs received 3 doses of sulfanegen sodium
      (2.5 g i.v.) every hour after induction of severe CN toxicity, and 4 pigs
      received placebo. NaCN study: A pilot study was conducted in 4 spontaneously
      ventilating pigs sedated with propofol plus ketamine to demonstrate hemodynamic
      and metabolic stability for several hours. After this, 6 pigs were similarly
      sedated and given NaCN in bolus aliquots to produce CN toxicity ultimately
      resulting in death. Hemodynamics and metabolic variables were followed to define
      peak CN toxicity. In another group of 6 pigs, severe CN toxicity was induced by
      this method, and at peak toxicity, the animals were given sulfanegen sodium (2.5
      g i.v.) followed by a repeat dose 60 minutes later in surviving animals. RESULTS:
      SNP study: The pilot study demonstrated the occurrence of a significant increase
      in blood CN levels (P < 0.05) accompanied by severe lactic acidemia (P < 0.05) in
      all pigs receiving a high dose of SNP. Administration of the sulfanegen antidote
      resulted in progressive significant reduction in blood lactate and CN levels with
      100% survival (P < 0.05), whereas the placebo-treated pigs deteriorated and did
      not survive (P < 0.05). NaCN study: NaCN injection resulted in CN toxicity
      accompanied by severe lactic acidosis and mortality in all the pigs. Sulfanegen
      sodium reversed this toxicity and prevented mortality in all the pigs treated
      with this antidote. CONCLUSIONS: CN toxicity can be successfully induced in a
      juvenile pig model with SNP or NaCN. The prodrug, sulfanegen sodium, is effective
      in reversing CN toxicity induced by SNP or NaCN.

PMID- 22392969
TI  - Prevention of paclitaxel-induced neuropathy through activation of the central
      cannabinoid type 2 receptor system.
AB  - BACKGROUND: Peripheral neuropathy is a major dose-limiting toxicity of
      chemotherapy, especially after multiple courses of paclitaxel. The development of
      paclitaxel-induced neuropathy is associated with the activation of microglia
      followed by the activation and proliferation of astrocytes, and the expression
      and release of proinflammatory cytokines in the spinal dorsal horn. Cannabinoid
      type 2 (CB(2)) receptors are expressed in the microglia in neurodegenerative
      disease models. METHODS: To explore the potential of CB(2) agonists for
      preventing paclitaxel-induced neuropathy, we designed and synthesized a novel
      CB(2)-selective agonist, namely, MDA7. The effect of MDA7 in preventing
      paclitaxel-induced allodynia was assessed in rats and in CB(2)(+/+) and CB(2)(-/
      ) mice. We hypothesized that the CB(2) receptor functions in a negative-feedback
      loop and that early MDA7 administration can blunt the neuroinflammatory response
      to paclitaxel and prevent mechanical allodynia through interference with specific
      signaling pathways. RESULTS: We found that MDA7 prevents paclitaxel-induced
      mechanical allodynia in rats and mice in a dose- and time-dependent manner
      without compromising paclitaxel's antineoplastic effect. MDA7's neuroprotective
      effect was absent in CB(2)(-/-) mice and was blocked by CB(2) antagonists,
      suggesting that MDA7's action directly involves CB(2) receptor activation. MDA7
      treatment was found to interfere with early events in the paclitaxel-induced
      neuroinflammatory response as evidenced by relatively reduced toll-like receptor
      and CB(2) expression in the lumbar spinal cord, reduced levels of extracellular
      signal-regulated kinase 1/2 activity, reduced numbers of activated microglia and
      astrocytes, and reduced secretion of proinflammatory mediators in vivo and in in
      vitro models. CONCLUSIONS: Our findings suggest an innovative therapeutic
      approach to prevent chemotherapy-induced neuropathy and may permit more
      aggressive use of active chemotherapeutic regimens with reduced long-term
      sequelae.

PMID- 22392972
TI  - Evaporation rate of water in hydrophobic confinement.
AB  - The drying of hydrophobic cavities is believed to play an important role in
      biophysical phenomena such as the folding of globular proteins, the opening and
      closing of ligand-gated ion channels, and ligand binding to hydrophobic pockets.
      We use forward flux sampling, a molecular simulation technique, to compute the
      rate of capillary evaporation of water confined between two hydrophobic surfaces
      separated by nanoscopic gaps, as a function of gap, surface size, and
      temperature. Over the range of conditions investigated (gaps between 9 and 14 A
      and surface areas between 1 and 9 nm(2)), the free energy barrier to evaporation
      scales linearly with the gap between hydrophobic surfaces, suggesting that line
      tension makes the predominant contribution to the free energy barrier. The
      exponential dependence of the evaporation rate on the gap between confining
      surfaces causes a 10 order-of-magnitude decrease in the rate when the gap
      increases from 9 to 14 A. The computed free energy barriers are of the order of
      50 kT and are predominantly enthalpic. Evaporation rates per unit area are found
      to be two orders of magnitude faster in confinement by the larger (9 nm(2)) than
      by the smaller (1 nm(2)) surfaces considered here, at otherwise identical
      conditions. We show that this rate enhancement is a consequence of the dependence
      of hydrophobic hydration on the size of solvated objects. For sufficiently large
      surfaces, the critical nucleus for the evaporation process is a gap-spanning
      vapor tube.

PMID- 22392974
TI  - Mechanism for Burgess Shale-type preservation.
AB  - Exceptionally preserved fossil biotas of the Burgess Shale and a handful of other
      similar Cambrian deposits provide rare but critical insights into the early
      diversification of animals. The extraordinary preservation of labile tissues in
      these geographically widespread but temporally restricted soft-bodied fossil
      assemblages has remained enigmatic since Walcott's initial discovery in 1909.
      Here, we demonstrate the mechanism of Burgess Shale-type preservation using
      sedimentologic and geochemical data from the Chengjiang, Burgess Shale, and five
      other principal Burgess Shale-type deposits. Sulfur isotope evidence from
      sedimentary pyrites reveals that the exquisite fossilization of organic remains
      as carbonaceous compressions resulted from early inhibition of microbial activity
      in the sediments by means of oxidant deprivation. Low sulfate concentrations in
      the global ocean and low-oxygen bottom water conditions at the sites of
      deposition resulted in reduced oxidant availability. Subsequently, rapid
      entombment of fossils in fine-grained sediments and early sealing of sediments by
      pervasive carbonate cements at bed tops restricted oxidant flux into the
      sediments. A permeability barrier, provided by bed-capping cements that were
      emplaced at the seafloor, is a feature that is shared among Burgess Shale-type
      deposits, and resulted from the unusually high alkalinity of Cambrian oceans.
      Thus, Burgess Shale-type preservation of soft-bodied fossil assemblages worldwide
      was promoted by unique aspects of early Paleozoic seawater chemistry that
      strongly impacted sediment diagenesis, providing a fundamentally unique record of
      the immediate aftermath of the "Cambrian explosion."

PMID- 22392973
TI  - Scanning probe-enabled nanocombinatorics define the relationship between
      fibronectin feature size and stem cell fate.
AB  - We report the development of a powerful analytical method that utilizes a tilted
      elastomeric pyramidal pen array in the context of a scanning probe lithography
      experiment to rapidly prepare libraries having as many as 25 million features
      over large areas with a range of feature sizes from the nano- to microscale. This
      technique can be used to probe important chemical and biological processes,
      opening up the field of nanocombinatorics. In a proof-of-concept investigation of
      mesenchymal stem cell (MSC) differentiation, combinatorial patterns first enabled
      a rapid and systematic screening of MSC adhesion, as a function of feature size,
      while uniform patterns were used to study differentiation with statistically
      significant sample sizes. Without media containing osteogenic-inducing chemical
      cues, cells cultured on nanopatterned fibronectin substrates direct MSC
      differentiation towards osteogenic fates when compared to nonpatterned
      fibronectin substrates. This powerful and versatile approach enables studies of
      many systems spanning biology, chemistry, and engineering areas.

PMID- 22392975
TI  - Folding mechanism of the metastable serpin alpha1-antitrypsin.
AB  - The misfolding of serpins is linked to several genetic disorders including
      emphysema, thrombosis, and dementia. During folding, inhibitory serpins are
      kinetically trapped in a metastable state in which a stretch of residues near the
      C terminus of the molecule are exposed to solvent as a flexible loop (the
      reactive center loop). When they inhibit target proteases, serpins transition to
      a stable state in which the reactive center loop forms part of a six-stranded
      beta-sheet. Here, we use hydrogen-deuterium exchange mass spectrometry to monitor
      region-specific folding of the canonical serpin human alpha(1)-antitrypsin
      (alpha(1)-AT). We find large differences in the folding kinetics of different
      regions. A key region in the metastable -> stable transition, beta-strand 5A,
      shows a lag phase of nearly 350 s. In contrast, the "B-C barrel" region shows no
      lag phase and the incorporation of the C-terminal residues into beta-sheets B and
      C is largely complete before the center of beta-sheet A begins to fold. We
      propose this as the mechanism for trapping alpha(1)-AT in a metastable form.
      Additionally, this separation of timescales in the folding of different regions
      suggests a mechanism by which alpha(1)-AT avoids polymerization during folding.

PMID- 22392976
TI  - A unified framework for non-brownian suspension flows and soft amorphous solids.
AB  - While the rheology of non-brownian suspensions in the dilute regime is well
      understood, their behavior in the dense limit remains mystifying. As the packing
      fraction of particles increases, particle motion becomes more collective, leading
      to a growing length scale and scaling properties in the rheology as the material
      approaches the jamming transition. There is no accepted microscopic description
      of this phenomenon. However, in recent years it has been understood that the
      elasticity of simple amorphous solids is governed by a critical point, the
      unjamming transition where the pressure vanishes, and where elastic properties
      display scaling and a diverging length scale. The correspondence between these
      two transitions is at present unclear. Here we show that for a simple model of
      dense flow, which we argue captures the essential physics near the jamming
      threshold, a formal analogy can be made between the rheology of the flow and the
      elasticity of simple networks. This analogy leads to a new conceptual framework
      to relate microscopic structure to rheology. It enables us to define and compute
      numerically normal modes and a density of states. We find striking similarities
      between the density of states in flow, and that of amorphous solids near
      unjamming: both display a plateau above some frequency scale omega(*) ~ |z(c) -
      z|, where z is the coordination of the network of particle in contact, z(c) = 2D
      where D is the spatial dimension. However, a spectacular difference appears: the
      density of states in flow displays a single mode at another frequency scale
      omega(min) ? omega(*) governing the divergence of the viscosity.

PMID- 22392977
TI  - Rapid self-healing hydrogels.
AB  - Synthetic materials that are capable of autonomous healing upon damage are being
      developed at a rapid pace because of their many potential applications. Despite
      these advancements, achieving self-healing in permanently cross-linked hydrogels
      has remained elusive because of the presence of water and irreversible cross
      links. Here, we demonstrate that permanently cross-linked hydrogels can be
      engineered to exhibit self-healing in an aqueous environment. We achieve this
      feature by arming the hydrogel network with flexible-pendant side chains carrying
      an optimal balance of hydrophilic and hydrophobic moieties that allows the side
      chains to mediate hydrogen bonds across the hydrogel interfaces with minimal
      steric hindrance and hydrophobic collapse. The self-healing reported here is
      rapid, occurring within seconds of the insertion of a crack into the hydrogel or
      juxtaposition of two separate hydrogel pieces. The healing is reversible and can
      be switched on and off via changes in pH, allowing external control over the
      healing process. Moreover, the hydrogels can sustain multiple cycles of healing
      and separation without compromising their mechanical properties and healing
      kinetics. Beyond revealing how secondary interactions could be harnessed to
      introduce new functions to chemically cross-linked polymeric systems, we also
      demonstrate various potential applications of such easy-to-synthesize, smart,
      self-healing hydrogels.

PMID- 22392978
TI  - Defining the molecular interface that connects the Fanconi anemia protein FANCM
      to the Bloom syndrome dissolvasome.
AB  - The RMI subcomplex (RMI1/RMI2) functions with the BLM helicase and topoisomerase
      IIIalpha in a complex called the "dissolvasome," which separates double-Holliday
      junction DNA structures that can arise during DNA repair. This activity
      suppresses potentially harmful sister chromatid exchange (SCE) events in wild
      type cells but not in cells derived from Bloom syndrome patients with
      inactivating BLM mutations. The RMI subcomplex also associates with FANCM, a
      component of the Fanconi anemia (FA) core complex that is important for repair of
      stalled DNA replication forks. The RMI/FANCM interface appears to help coordinate
      dissolvasome and FA core complex activities, but its precise role remains poorly
      understood. Here, we define the structure of the RMI/FANCM interface and
      investigate its roles in coordinating cellular DNA-repair activities. The X-ray
      crystal structure of the RMI core complex bound to a well-conserved peptide from
      FANCM shows that FANCM binds to both RMI proteins through a hydrophobic "knobs
      into-holes" packing arrangement. The RMI/FANCM interface is shown to be critical
      for interaction between the components of the dissolvasome and the FA core
      complex. FANCM variants that substitute alanine for key interface residues
      strongly destabilize the complex in solution and lead to increased SCE levels in
      cells that are similar to those observed in blm- or fancm-deficient cells. This
      study provides a molecular view of the RMI/FANCM complex and highlights a key
      interface utilized in coordinating the activities of two critical eukaryotic DNA
      damage repair machines.

PMID- 22392979
TI  - Droplet formation and scaling in dense suspensions.
AB  - When a dense suspension is squeezed from a nozzle, droplet detachment can occur
      similar to that of pure liquids. While in pure liquids the process of droplet
      detachment is well characterized through self-similar profiles and known scaling
      laws, we show here the simple presence of particles causes suspensions to break
      up in a new fashion. Using high-speed imaging, we find that detachment of a
      suspension drop is described by a power law; specifically we find the neck
      minimum radius, r(m), scales like near breakup at time tau = 0. We demonstrate
      data collapse in a variety of particle/liquid combinations, packing fractions,
      solvent viscosities, and initial conditions. We argue that this scaling is a
      consequence of particles deforming the neck surface, thereby creating a pressure
      that is balanced by inertia, and show how it emerges from topological constraints
      that relate particle configurations with macroscopic Gaussian curvature. This new
      type of scaling, uniquely enforced by geometry and regulated by the particles,
      displays memory of its initial conditions, fails to be self-similar, and has
      implications for the pressure given at generic suspension interfaces.

PMID- 22392980
TI  - Evidence from central Mexico supporting the Younger Dryas extraterrestrial impact
      hypothesis.
AB  - We report the discovery in Lake Cuitzeo in central Mexico of a black, carbon
      rich, lacustrine layer, containing nanodiamonds, microspherules, and other
      unusual materials that date to the early Younger Dryas and are interpreted to
      result from an extraterrestrial impact. These proxies were found in a 27-m-long
      core as part of an interdisciplinary effort to extract a paleoclimate record back
      through the previous interglacial. Our attention focused early on an anomalous,
      10-cm-thick, carbon-rich layer at a depth of 2.8 m that dates to 12.9 ka and
      coincides with a suite of anomalous coeval environmental and biotic changes
      independently recognized in other regional lake sequences. Collectively, these
      changes have produced the most distinctive boundary layer in the late Quaternary
      record. This layer contains a diverse, abundant assemblage of impact-related
      markers, including nanodiamonds, carbon spherules, and magnetic spherules with
      rapid melting/quenching textures, all reaching synchronous peaks immediately
      beneath a layer containing the largest peak of charcoal in the core. Analyses by
      multiple methods demonstrate the presence of three allotropes of nanodiamond: n
      diamond, i-carbon, and hexagonal nanodiamond (lonsdaleite), in order of estimated
      relative abundance. This nanodiamond-rich layer is consistent with the Younger
      Dryas boundary layer found at numerous sites across North America, Greenland, and
      Western Europe. We have examined multiple hypotheses to account for these
      observations and find the evidence cannot be explained by any known terrestrial
      mechanism. It is, however, consistent with the Younger Dryas boundary impact
      hypothesis postulating a major extraterrestrial impact involving multiple
      airburst(s) and and/or ground impact(s) at 12.9 ka.

PMID- 22392981
TI  - Stoichiometry of proton translocation by respiratory complex I and its
      mechanistic implications.
AB  - Complex I (NADH-ubiquinone oxidoreductase) in the respiratory chain of
      mitochondria and several bacteria functions as a redox-driven proton pump that
      contributes to the generation of the protonmotive force across the inner
      mitochondrial or bacterial membrane and thus to the aerobic synthesis of ATP. The
      stoichiometry of proton translocation is thought to be 4 H(+) per NADH oxidized
      (2 e(-)). Here we show that a H(+)/2 e(-) ratio of 3 appears more likely on the
      basis of the recently determined H(+)/ATP ratio of the mitochondrial F(1)F(o)-ATP
      synthase of animal mitochondria and of a set of carefully determined ATP/2 e(-)
      ratios for different segments of the mitochondrial respiratory chain. This lower
      H(+)/2 e(-) ratio of 3 is independently supported by thermodynamic analyses of
      experiments with both mitochondria and submitochondrial particles. A reduced
      H(+)/2 e(-) stoichiometry of 3 has important mechanistic implications for this
      proton pump. In a rough mechanistic model, we suggest a concerted proton
      translocation mechanism in the three homologous and tightly packed antiporter
      like subunits L, M, and N of the proton-translocating membrane domain of complex
      I.

PMID- 22392982
TI  - Lipophilic analogs of zoledronate and risedronate inhibit Plasmodium
      geranylgeranyl diphosphate synthase (GGPPS) and exhibit potent antimalarial
      activity.
AB  - We report the results of an in vitro screening assay targeting the
      intraerythrocytic form of the malaria parasite Plasmodium falciparum using a
      library of 560 prenyl-synthase inhibitors. Based on "growth-rescue" and enzyme
      inhibition experiments, geranylgeranyl diphosphate synthase (GGPPS) is shown to
      be a major target for the most potent leads, BPH-703 and BPH-811, lipophilic
      analogs of the bone-resorption drugs zoledronate and risedronate. We determined
      the crystal structures of these inhibitors bound to a Plasmodium GGPPS finding
      that their head groups bind to the [Mg(2+)](3) cluster in the active site in a
      similar manner to that found with their more hydrophilic parents, whereas their
      hydrophobic tails occupy a long-hydrophobic tunnel spanning both molecules in the
      dimer. The results of isothermal-titration-calorimetric experiments show that
      both lipophilic bisphosphonates bind to GGPPS with, on average, a DeltaG of -9
      kcal mol(-1), only 0.5 kcal mol(-1) worse than the parent bisphosphonates,
      consistent with the observation that conversion to the lipophilic species has
      only a minor effect on enzyme activity. However, only the lipophilic species are
      active in cells. We also tested both compounds in mice, finding major decreases
      in parasitemia and 100% survival. These results are of broad general interest
      because they indicate that it may be possible to overcome barriers to cell
      penetration of existing bisphosphonate drugs in this and other systems by simple
      covalent modification to form lipophilic analogs that retain their enzyme
      inhibition activity and are also effective in vitro and in vivo.

PMID- 22392983
TI  - Homology models guide discovery of diverse enzyme specificities among dipeptide
      epimerases in the enolase superfamily.
AB  - The rapid advance in genome sequencing presents substantial challenges for
      protein functional assignment, with half or more of new protein sequences
      inferred from these genomes having uncertain assignments. The assignment of
      enzyme function in functionally diverse superfamilies represents a particular
      challenge, which we address through a combination of computational predictions,
      enzymology, and structural biology. Here we describe the results of a focused
      investigation of a group of enzymes in the enolase superfamily that are involved
      in epimerizing dipeptides. The first members of this group to be functionally
      characterized were Ala-Glu epimerases in Eschericiha coli and Bacillus subtilis,
      based on the operon context and enzymological studies; these enzymes are presumed
      to be involved in peptidoglycan recycling. We have subsequently studied more than
      65 related enzymes by computational methods, including homology modeling and
      metabolite docking, which suggested that many would have divergent
      specificities;, i.e., they are likely to have different (unknown) biological
      roles. In addition to the Ala-Phe epimerase specificity reported previously, we
      describe the prediction and experimental verification of: (i) a new group of
      presumed Ala-Glu epimerases; (ii) several enzymes with specificity for
      hydrophobic dipeptides, including one from Cytophaga hutchinsonii that epimerizes
      D-Ala-D-Ala; and (iii) a small group of enzymes that epimerize cationic
      dipeptides. Crystal structures for certain of these enzymes further elucidate the
      structural basis of the specificities. The results highlight the potential of
      computational methods to guide experimental characterization of enzymes in an
      automated, large-scale fashion.

PMID- 22392984
TI  - Focused ion beam micromachining of eukaryotic cells for cryoelectron tomography.
AB  - Cryoelectron tomography provides unprecedented insights into the macromolecular
      and supramolecular organization of cells in a close-to-living state. However
      because of the limited thickness range (< 0.5-1 MUm) that is accessible with
      today's intermediate voltage electron microscopes only small prokaryotic cells or
      peripheral regions of eukaryotic cells can be examined directly. Key to
      overcoming this limitation is the ability to prepare sufficiently thin samples.
      Cryosectioning can be used to prepare thin enough sections but suffers from
      severe artefacts, such as substantial compression. Here we describe a procedure,
      based upon focused ion beam (FIB) milling for the preparation of thin (200-500
      nm) lamellae from vitrified cells grown on electron microscopy (EM) grids. The
      self-supporting lamellae are apparently free of distortions or other artefacts
      and open up large windows into the cell's interior allowing tomographic studies
      to be performed on any chosen part of the cell. We illustrate the quality of
      sample preservation with a structure of the nuclear pore complex obtained from a
      single tomogram.

PMID- 22392985
TI  - Isotope composition and volume of Earth's early oceans.
AB  - Oxygen and hydrogen isotope compositions of Earth's seawater are controlled by
      volatile fluxes among mantle, lithospheric (oceanic and continental crust), and
      atmospheric reservoirs. Throughout geologic time the oxygen mass budget was
      likely conserved within these Earth system reservoirs, but hydrogen's was not, as
      it can escape to space. Isotopic properties of serpentine from the approximately
      3.8 Ga Isua Supracrustal Belt in West Greenland are used to characterize hydrogen
      and oxygen isotope compositions of ancient seawater. Archaean oceans were
      depleted in deuterium [expressed as deltaD relative to Vienna standard mean ocean
      water (VSMOW)] by at most 25 +/- 50/00, but oxygen isotope ratios were comparable
      to modern oceans. Mass balance of the global hydrogen budget constrains the
      contribution of continental growth and planetary hydrogen loss to the secular
      evolution of hydrogen isotope ratios in Earth's oceans. Our calculations predict
      that the oceans of early Earth were up to 26% more voluminous, and atmospheric
      CH(4) and CO(2) concentrations determined from limits on hydrogen escape to space
      are consistent with clement conditions on Archaean Earth.

PMID- 22392986
TI  - Phase separation and rotor self-assembly in active particle suspensions.
AB  - Adding a nonadsorbing polymer to passive colloids induces an attraction between
      the particles via the "depletion" mechanism. High enough polymer concentrations
      lead to phase separation. We combine experiments, theory, and simulations to
      demonstrate that using active colloids (such as motile bacteria) dramatically
      changes the physics of such mixtures. First, significantly stronger interparticle
      attraction is needed to cause phase separation. Secondly, the finite size
      aggregates formed at lower interparticle attraction show unidirectional rotation.
      These micro-rotors demonstrate the self-assembly of functional structures using
      active particles. The angular speed of the rotating clusters scales approximately
      as the inverse of their size, which may be understood theoretically by assuming
      that the torques exerted by the outermost bacteria in a cluster add up randomly.
      Our simulations suggest that both the suppression of phase separation and the
      self-assembly of rotors are generic features of aggregating swimmers and should
      therefore occur in a variety of biological and synthetic active particle systems.

PMID- 22392987
TI  - Mammalian X chromosome inactivation evolved as a dosage-compensation mechanism
      for dosage-sensitive genes on the X chromosome.
AB  - How and why female somatic X-chromosome inactivation (XCI) evolved in mammals
      remains poorly understood. It has been proposed that XCI is a dosage-compensation
      mechanism that evolved to equalize expression levels of X-linked genes in females
      (2X) and males (1X), with a prior twofold increase in expression of X-linked
      genes in both sexes ("Ohno's hypothesis"). Whereas the parity of X chromosome
      expression between the sexes has been clearly demonstrated, tests for the
      doubling of expression levels globally along the X chromosome have returned
      contradictory results. However, changes in gene dosage during sex-chromosome
      evolution are not expected to impact on all genes equally, and should have
      greater consequences for dosage-sensitive genes. We show that, for genes encoding
      components of large protein complexes (>= 7 members)--a class of genes that is
      expected to be dosage-sensitive--expression of X-linked genes is similar to that
      of autosomal genes within the complex. These data support Ohno's hypothesis that
      XCI acts as a dosage-compensation mechanism, and allow us to refine Ohno's model
      of XCI evolution. We also explore the contribution of dosage-sensitive genes to X
      aneuploidy phenotypes in humans, such as Turner (X0) and Klinefelter (XXY)
      syndromes. X aneuploidy in humans is common and is known to have mild effects
      because most of the supernumerary X genes are inactivated and not affected by
      aneuploidy. Only genes escaping XCI experience dosage changes in X-aneuploidy
      patients. We combined data on dosage sensitivity and XCI to compute a list of
      candidate genes for X-aneuploidy syndromes.

PMID- 22392988
TI  - Incorporation of new information into prefrontal cortical activity after learning
      working memory tasks.
AB  - The ability to learn new tasks requires that new information is integrated into
      neural systems that already support other behaviors. To study how new information
      is incorporated into neural representations, we analyzed single-unit recordings
      from the prefrontal cortex (PFC), a brain region important for task acquisition
      and working memory, before and after monkeys learned to perform two behavioral
      tasks. A population-decoding analysis revealed a large increase in task-relevant
      information, and smaller changes in stimulus-related information, after training.
      This new information was contained in dynamic patterns of neural activity, with
      many individual neurons containing the new task-relevant information for only
      relatively short periods of time in the midst of other large firing rate
      modulations. Additionally, we found that stimulus information could be decoded
      with high accuracy only from dorsal PFC, whereas task-relevant information was
      distributed throughout both dorsal and ventral PFC. These findings help resolve a
      controversy about whether PFC is innately specialized to process particular types
      of information or whether its responses are completely determined by task demands
      by showing there is both regional specialization within PFC that was present
      before training, as well as more widespread task-relevant information that is a
      direct result of learning. The results also show that information is incorporated
      into PFC through the emergence of a small population of highly selective neurons
      that overlay new signals on top of patterns of activity that contain information
      about previously encoded variables, which gives insight into how information is
      coded in neural activity.

PMID- 22392989
TI  - Early ontogenic origin of the hematopoietic stem cell lineage.
AB  - Several lines of evidence suggest that the adult hematopoietic system has
      multiple developmental origins, but the ontogenic relationship between nascent
      hematopoietic populations under this scheme is poorly understood. In an
      alternative theory, the earliest definitive blood precursors arise from a single
      anatomical location, which constitutes the cellular source for subsequent
      hematopoietic populations. To deconvolute hematopoietic ontogeny, we designed an
      embryo-rescue system in which the key hematopoietic factor Runx1 is reactivated
      in Runx1-null conceptuses at specific developmental stages. Using complementary
      in vivo and ex vivo approaches, we provide evidence that definitive hematopoiesis
      and adult-type hematopoietic stem cells originate predominantly in the nascent
      extraembryonic mesoderm. Our data also suggest that other anatomical sites that
      have been proposed to be sources of the definitive hematopoietic hierarchy are
      unlikely to play a substantial role in de novo blood generation.

PMID- 22392990
TI  - On a fundamental structure of gene networks in living cells.
AB  - Computers are organized into hardware and software. Using a theoretical approach
      to identify patterns in gene expression in a variety of species, organs, and cell
      types, we found that biological systems similarly are comprised of a relatively
      unchanging hardware-like gene pattern. Orthogonal patterns of software-like
      transcripts vary greatly, even among tumors of the same type from different
      individuals. Two distinguishable classes could be identified within the hardware
      like component: those transcripts that are highly expressed and stable and an
      adaptable subset with lower expression that respond to external stimuli.
      Importantly, we demonstrate that this structure is conserved across organisms.
      Deletions of transcripts from the highly stable core are predicted to result in
      cell mortality. The approach provides a conceptual thermodynamic-like framework
      for the analysis of gene-expression levels and networks and their variations in
      diseased cells.

PMID- 22392991
TI  - Combined linkage and association mapping reveals CYCD5;1 as a quantitative trait
      gene for endoreduplication in Arabidopsis.
AB  - Endoreduplication is the process where a cell replicates its genome without
      mitosis and cytokinesis, often followed by cell differentiation. This alternative
      cell cycle results in various levels of endoploidy, reaching 4* or higher one
      haploid set of chromosomes. Endoreduplication is found in animals and is
      widespread in plants, where it plays a major role in cellular differentiation and
      plant development. Here, we show that variation in endoreduplication between
      Arabidopsis thaliana accessions Columbia-0 and Kashmir is controlled by two major
      quantitative trait loci, ENDO-1 and ENDO-2. A local candidate gene association
      analysis in a set of 87 accessions, combined with expression analysis, identified
      CYCD5;1 as the most likely candidate gene underlying ENDO-2, operating as a rate
      determining factor of endoreduplication. In accordance, both the overexpression
      and silencing of CYCD5;1 were effective in changing DNA ploidy levels, confirming
      CYCD5;1 to be a previously undescribed quantitative trait gene underlying
      endoreduplication in Arabidopsis.

PMID- 22392992
TI  - Chemokine receptor CXCR3 agonist prevents human T-cell migration in a humanized
      model of arthritic inflammation.
AB  - The recruitment of T lymphocytes during diseases such as rheumatoid arthritis is
      regulated by stimulation of the chemokine receptors expressed by these cells.
      This study was designed to assess the potential of a CXCR3-specific small
      molecule agonist to inhibit the migration of activated human T cells toward
      multiple chemokines. Further experiments defined the molecular mechanism for this
      anti-inflammatory activity. Analysis in vitro demonstrated agonist induced
      internalization of both CXCR3 and other chemokine receptors coexpressed by
      CXCR3(+) T cells. Unlike chemokine receptor-specific antagonists, the CXCR3
      agonist inhibited migration of activated T cells toward the chemokine mixture in
      synovial fluid from patients with active rheumatoid arthritis. A humanized mouse
      air-pouch model showed that intravenous treatment with the CXCR3 agonist
      prevented inflammatory migration of activated human T cells toward this synovial
      fluid. A potential mechanism for this action was defined by demonstration that
      the CXCR3 agonist induces receptor cross-phosphorylation within CXCR3-CCR5
      heterodimers on the surface of activated T cells. This study shows that
      generalized chemokine receptor desensitization can be induced by specific
      stimulation of a single chemokine receptor on the surface of activated human T
      cells. A humanized mouse model was used to demonstrate that this receptor
      desensitization inhibits the inflammatory response that is normally produced by
      the chemokines present in synovial fluid from patients with active rheumatoid
      arthritis.

PMID- 22392993
TI  - Neuronal mRNAs travel singly into dendrites.
AB  - RNA transport granules deliver translationally repressed mRNAs to synaptic sites
      in dendrites, where synaptic activity promotes their localized translation.
      Although the identity of many proteins that make up the neuronal granules is
      known, the stoichiometry of their core component, the mRNA, is poorly understood.
      By imaging nine different dendritically localized mRNA species with single
      molecule sensitivity and subdiffraction-limit resolution in cultured hippocampal
      neurons, we show that two molecules of the same or different mRNA species do not
      assemble in common structures. Even mRNA species with a common dendritic
      localization element, the sequence that is believed to mediate the incorporation
      of these mRNAs into common complexes, do not colocalize. These results suggest
      that mRNA molecules traffic to the distal reaches of dendrites singly and
      independently of others, a model that permits a finer control of mRNA content
      within a synapse for synaptic plasticity.

PMID- 22392994
TI  - X-ray repair cross-complementing protein 1 (XRCC1) deficiency enhances class
      switch recombination and is permissive for alternative end joining.
AB  - DNA double-strand breaks (DSBs) are essential intermediates in Ig gene
      rearrangements: V(D)J and class switch recombination (CSR). In contrast to V(D)J
      recombination, which is almost exclusively dependent on nonhomologous end joining
      (NHEJ), CSR can occur in NHEJ-deficient cells via a poorly understand backup
      pathway (or pathways) often termed alternative end joining (A-EJ). Recently,
      several components of the single-strand DNA break (SSB) repair machinery,
      including XRCC1, have been implicated in A-EJ. To determine its role in A-EJ and
      CSR, Xrcc1 was deleted by targeted mutation in the CSR proficient mouse B-cell
      line, CH12F3. Here we demonstrate that XRCC1 deficiency slightly increases the
      efficiency of CSR. More importantly, Lig4 and XRCC1 double-deficient cells switch
      as efficiently as Lig4-deficient cells, clearly indicating that XRCC1 is
      dispensable for A-EJ in CH12F3 cells during CSR.

PMID- 22392996
TI  - Ecosystem service tradeoff analysis reveals the value of marine spatial planning
      for multiple ocean uses.
AB  - Marine spatial planning (MSP) is an emerging responsibility of resource managers
      around the United States and elsewhere. A key proposed advantage of MSP is that
      it makes tradeoffs in resource use and sector (stakeholder group) values
      explicit, but doing so requires tools to assess tradeoffs. We extended tradeoff
      analyses from economics to simultaneously assess multiple ecosystem services and
      the values they provide to sectors using a robust, quantitative, and transparent
      framework. We used the framework to assess potential conflicts among offshore
      wind energy, commercial fishing, and whale-watching sectors in Massachusetts and
      identify and quantify the value from choosing optimal wind farm designs that
      minimize conflicts among these sectors. Most notably, we show that using MSP over
      conventional planning could prevent >$1 million dollars in losses to the
      incumbent fishery and whale-watching sectors and could generate >$10 billion in
      extra value to the energy sector. The value of MSP increased with the greater the
      number of sectors considered and the larger the area under management.
      Importantly, the framework can be applied even when sectors are not measured in
      dollars (e.g., conservation). Making tradeoffs explicit improves transparency in
      decision-making, helps avoid unnecessary conflicts attributable to perceived but
      weak tradeoffs, and focuses debate on finding the most efficient solutions to
      mitigate real tradeoffs and maximize sector values. Our analysis demonstrates the
      utility, feasibility, and value of MSP and provides timely support for the
      management transitions needed for society to address the challenges of an
      increasingly crowded ocean environment.

PMID- 22392997
TI  - Neutral theory for life histories and individual variability in fitness
      components.
AB  - Individuals within populations can differ substantially in their life span and
      their lifetime reproductive success but such realized individual variation in
      fitness components need not reflect underlying heritable fitness differences
      visible to natural selection. Even so, biologists commonly argue that large
      differences in fitness components are likely adaptive, resulting from and driving
      evolution by natural selection. To examine this argument we use unique formulas
      to compute exactly the variance in life span and in lifetime reproductive success
      among individuals with identical (genotypic) vital rates (assuming a common
      genotype for all individuals). Such individuals have identical fitness but vary
      substantially in their realized individual fitness components. We show by example
      that our computed variances and corresponding simulated distribution of fitness
      components match those observed in real populations. Of course, (genotypic) vital
      rates in real populations are expected to differ by small but evolutionarily
      important amounts among genotypes, but we show that such differences only
      modestly increase variances in fitness components. We conclude that observed
      differences in fitness components may likely be evolutionarily neutral, at least
      to the extent that they are indistinguishable from distributions generated by
      neutral processes. Important consequences of large neutral variation are the
      following: Heritabilities for fitness components are likely to be small (which is
      in fact the case), small selective differences in life histories will be hard to
      measure, and the effects of random drift will be amplified in natural populations
      by the large variances among individuals.

PMID- 22392995
TI  - Constraint shapes convergence in tetrodotoxin-resistant sodium channels of
      snakes.
AB  - Natural selection often produces convergent changes in unrelated lineages, but
      the degree to which such adaptations occur via predictable genetic paths is
      unknown. If only a limited subset of possible mutations is fixed in independent
      lineages, then it is clear that constraint in the production or function of
      molecular variants is an important determinant of adaptation. We demonstrate
      remarkably constrained convergence during the evolution of resistance to the
      lethal poison, tetrodotoxin, in six snake species representing three distinct
      lineages from around the globe. Resistance-conferring amino acid substitutions in
      a voltage-gated sodium channel, Na(v)1.4, are clustered in only two regions of
      the protein, and a majority of the replacements are confined to the same three
      positions. The observed changes represent only a small fraction of the
      experimentally validated mutations known to increase Na(v)1.4 resistance to
      tetrodotoxin. These results suggest that constraints resulting from functional
      tradeoffs between ion channel function and toxin resistance led to predictable
      patterns of evolutionary convergence at the molecular level. Our data are
      consistent with theoretical predictions and recent microcosm work that suggest a
      predictable path is followed during an adaptive walk along a mutational
      landscape, and that natural selection may be frequently constrained to produce
      similar genetic outcomes even when operating on independent lineages.

PMID- 22392998
TI  - Inhibition of cytochrome P4501-dependent clearance of the endogenous agonist FICZ
      as a mechanism for activation of the aryl hydrocarbon receptor.
AB  - Altered systemic levels of 6-formylindolo[3,2-b]carbazole (FICZ), an enigmatic
      endogenous ligand for the aryl hydrocarbon receptor (AHR), may explain adverse
      physiological responses evoked by small natural and anthropogenic molecules as
      well as by oxidative stress and light. We demonstrate here that several different
      chemical compounds can inhibit the metabolism of FICZ, thereby disrupting the
      autoregulatory feedback control of cytochrome P4501 systems and other proteins
      whose expression is regulated by AHR. FICZ is both the most tightly bound
      endogenous agonist for the AHR and an ideal substrate for cytochrome CYP1A1/1A2
      and 1B1, thereby also participating in an autoregulatory loop that keeps its own
      steady-state concentration low. At very low concentrations FICZ influences
      circadian rhythms, responses to UV light, homeostasis associated with pro- and
      anti-inflammatory processes, and genomic stability. Here, we demonstrate that, if
      its metabolic clearance is compromised, femtomolar background levels of this
      compound in cell-culture medium are sufficient to up-regulate CYP1A1 mRNA and
      enzyme activity. The oxidants UVB irradiation and hydrogen peroxide and the model
      AHR antagonist 3'-methoxy-4'-nitroflavone all inhibited induction of CYP1A1
      enzyme activity by FICZ or 2,3,7,8-tetrachlorodibenzo-p-dioxin, thereby
      subsequently elevating intracellular levels of FICZ and activating AHR. Taken
      together, these findings support an indirect mechanism of AHR activation,
      indicating that AHR activation by molecules with low affinity actually may
      reflect inhibition of FICZ metabolism and raising questions about the reported
      promiscuity of the AHR. Accordingly, we propose that prolonged induction of AHR
      activity through inhibition of CYP1 disturbs feedback regulation of FICZ levels,
      with potential detrimental consequences.

PMID- 22392999
TI  - Wnt/beta-catenin signaling promotes differentiation, not self-renewal, of human
      embryonic stem cells and is repressed by Oct4.
AB  - Signal transduction pathways play diverse, context-dependent roles in vertebrate
      development. In studies of human embryonic stem cells (hESCs), conflicting
      reports claim Wnt/beta-catenin signaling promotes either self-renewal or
      differentiation. We use a sensitive reporter to establish that Wnt/beta-catenin
      signaling is not active during hESC self-renewal. Inhibiting this pathway over
      multiple passages has no detrimental effect on hESC maintenance, whereas
      activating signaling results in loss of self-renewal and induction of mesoderm
      lineage genes. Following exposure to pathway agonists, hESCs exhibit a delay in
      activation of beta-catenin signaling, which led us to postulate that Wnt/beta
      catenin signaling is actively repressed during self-renewal. In support of this
      hypothesis, we demonstrate that OCT4 represses beta-catenin signaling during self
      renewal and that targeted knockdown of OCT4 activates beta-catenin signaling in
      hESCs. Using a fluorescent reporter of beta-catenin signaling in live hESCs, we
      observe that the reporter is activated in a very heterogeneous manner in response
      to stimulation with Wnt ligand. Sorting cells on the basis of their fluorescence
      reveals that hESCs with elevated beta-catenin signaling express higher levels of
      differentiation markers. Together these data support a dominant role for Wnt/beta
      catenin signaling in the differentiation rather than self-renewal of hESCs.

PMID- 22393000
TI  - Nonmuscle myosin II exerts tension but does not translocate actin in vertebrate
      cytokinesis.
AB  - During vertebrate cytokinesis it is thought that contractile ring constriction is
      driven by nonmuscle myosin II (NM II) translocation of antiparallel actin
      filaments. Here we report in situ, in vitro, and in vivo observations that
      challenge this hypothesis. Graded knockdown of NM II in cultured COS-7 cells
      reveals that the amount of NM II limits ring constriction. Restoration of the
      constriction rate with motor-impaired NM II mutants shows that the ability of NM
      II to translocate actin is not required for cytokinesis. Blebbistatin inhibition
      of cytokinesis indicates the importance of myosin strongly binding to actin and
      exerting tension during cytokinesis. This role is substantiated by transient
      kinetic experiments showing that the load-dependent mechanochemical properties of
      mutant NM II support efficient tension maintenance despite the inability to
      translocate actin. Under loaded conditions, mutant NM II exhibits a prolonged
      actin attachment in which a single mechanoenzymatic cycle spans most of the time
      of cytokinesis. This prolonged attachment promotes simultaneous binding of NM II
      heads to actin, thereby increasing tension and resisting expansion of the ring.
      The detachment of mutant NM II heads from actin is enhanced by assisting loads,
      which prevent mutant NM II from hampering furrow ingression during cytokinesis.
      In the 3D context of mouse hearts, mutant NM II-B R709C that cannot translocate
      actin filaments can rescue multinucleation in NM II-B ablated cardiomyocytes. We
      propose that the major roles of NM II in vertebrate cell cytokinesis are to bind
      and cross-link actin filaments and to exert tension on actin during contractile
      ring constriction.

PMID- 22393001
TI  - Trading-off fish biodiversity, food security, and hydropower in the Mekong River
      Basin.
AB  - The Mekong River Basin, site of the biggest inland fishery in the world, is
      undergoing massive hydropower development. Planned dams will block critical fish
      migration routes between the river's downstream floodplains and upstream
      tributaries. Here we estimate fish biomass and biodiversity losses in numerous
      damming scenarios using a simple ecological model of fish migration. Our
      framework allows detailing trade-offs between dam locations, power production,
      and impacts on fish resources. We find that the completion of 78 dams on
      tributaries, which have not previously been subject to strategic analysis, would
      have catastrophic impacts on fish productivity and biodiversity. Our results
      argue for reassessment of several dams planned, and call for a new regional
      agreement on tributary development of the Mekong River Basin.

PMID- 22393002
TI  - Transferred melanoma-specific CD8+ T cells persist, mediate tumor regression, and
      acquire central memory phenotype.
AB  - Adoptively transferred tumor-specific T cells offer the potential for non-cross
      resistant therapy and long-term immunoprotection. Strategies to enhance in vivo
      persistence of transferred T cells can lead to improved antitumor efficacy.
      However, the extrinsic (patient conditioning) and intrinsic (effector cell)
      factors contributing to long-term in vivo persistence are not well-defined. As a
      means to enhance persistence of infused T cells in vivo and limit toxicity, 11
      patients with refractory, progressive metastatic melanoma received
      cyclophosphamide alone as conditioning before the infusion of peripheral blood
      mononuclear cell-derived, antigen-specific, CD8(+) cytotoxic T-lymphocyte (CTL)
      clones followed by low-dose or high-dose IL-2. No life-threatening toxicities
      occurred with low-dose IL-2. Five of 10 evaluable patients had stable disease at
      8 wk, and 1 of 11 had a complete remission that continued for longer than 3 y. On
      target autoimmune events with the early appearance of skin rashes were observed
      in patients with stable disease or complete remission at 4 wk or longer. In vivo
      tracking revealed that the conditioning regimen provided a favorable milieu that
      enabled CTL proliferation early after transfer and localization to nonvascular
      compartments, such as skin and lymph nodes. CTL clones, on infusion, were
      characterized by an effector memory phenotype, and CTL that persisted long term
      acquired phenotypic and/or functional qualities of central memory type CTLs in
      vivo. The use of a T-cell product composed of a clonal population of antigen
      specific CTLs afforded the opportunity to demonstrate phenotypic and/or
      functional conversion to a central memory type with the potential for sustained
      clinical benefit.

PMID- 22393003
TI  - Continent-wide risk assessment for the establishment of nonindigenous species in
      Antarctica.
AB  - Invasive alien species are among the primary causes of biodiversity change
      globally, with the risks thereof broadly understood for most regions of the
      world. They are similarly thought to be among the most significant conservation
      threats to Antarctica, especially as climate change proceeds in the region.
      However, no comprehensive, continent-wide evaluation of the risks to Antarctica
      posed by such species has been undertaken. Here we do so by sampling,
      identifying, and mapping the vascular plant propagules carried by all categories
      of visitors to Antarctica during the International Polar Year's first season
      (2007-2008) and assessing propagule establishment likelihood based on their
      identity and origins and on spatial variation in Antarctica's climate. For an
      evaluation of the situation in 2100, we use modeled climates based on the
      Intergovernmental Panel on Climate Change's Special Report on Emissions Scenarios
      Scenario A1B [Nakicenovic N, Swart R, eds (2000) Special Report on Emissions
      Scenarios: A Special Report of Working Group III of the Intergovernmental Panel
      on Climate Change (Cambridge University Press, Cambridge, UK)]. Visitors carrying
      seeds average 9.5 seeds per person, although as vectors, scientists carry greater
      propagule loads than tourists. Annual tourist numbers (~33,054) are higher than
      those of scientists (~7,085), thus tempering these differences in propagule load.
      Alien species establishment is currently most likely for the Western Antarctic
      Peninsula. Recent founder populations of several alien species in this area
      corroborate these findings. With climate change, risks will grow in the Antarctic
      Peninsula, Ross Sea, and East Antarctic coastal regions. Our evidence-based
      assessment demonstrates which parts of Antarctica are at growing risk from alien
      species that may become invasive and provides the means to mitigate this threat
      now and into the future as the continent's climate changes.

PMID- 22393004
TI  - Quantitative global analysis of the role of climate and people in explaining late
      Quaternary megafaunal extinctions.
AB  - The late Quaternary period saw the rapid extinction of the majority of the
      world's terrestrial megafauna. The cause of these dramatic losses, especially the
      relative importance of climatic change and the impacts of newly arrived people,
      remains highly controversial, with geographically restricted analyses generating
      conflicting conclusions. By analyzing the distribution and timing of all
      megafaunal extinctions in relation to climatic variables and human arrival on
      five landmasses, we demonstrate that the observed pattern of extinctions is best
      explained by models that combine both human arrival and climatic variables. Our
      conclusions are robust to uncertainties in climate data and in the dates of
      megafaunal extinctions and human arrival on different landmasses, and strongly
      suggest that these extinctions were driven by both anthropogenic and climatic
      factors.

PMID- 22393005
TI  - Bid-induced mitochondrial membrane permeabilization waves propagated by local
      reactive oxygen species (ROS) signaling.
AB  - Bid-induced mitochondrial membrane permeabilization and cytochrome c release are
      central to apoptosis. It remains a mystery how tiny amounts of Bid synchronize
      the function of a large number of discrete organelles, particularly in
      mitochondria-rich cells. Looking at cell populations, the rate and lag time of
      the Bid-induced permeabilization are dose-dependent, but even very low doses lead
      eventually to complete cytochrome c release. By contrast, individual mitochondria
      display relatively rapid and uniform kinetics, indicating that the dose
      dependence seen in populations is due to a spreading of individual events in
      time. We report that Bid-induced permeabilization and cytochrome c release
      regularly demonstrate a wave-like pattern, propagating through a cell at a
      constant velocity without dissipation. Such waves do not depend on caspase
      activation or permeability transition pore opening. However, reactive oxygen
      species (ROS) scavengers suppressed the coordination of cytochrome c release and
      also inhibited Bid-induced cell death, whereas both superoxide and hydrogen
      peroxide sensitized mitochondria to Bid-induced permeabilization. Thus, Bid
      engages a ROS-dependent, local intermitochondrial potentiation mechanism that
      amplifies the apoptotic signal as a wave.

PMID- 22393006
TI  - Bitrophic interactions shape biodiversity in space.
AB  - Ecologists and conservation biologists often study particular trophic groups in
      isolation, which precludes an explicit assessment of the impact of multitrophic
      interactions on community structure and dynamics. Network ecology helps to fill
      this gap by focusing on species interactions, but it often ignores spatial
      processes. Here, we are taking a step forward in the integration of metacommunity
      and network approaches by studying a model of bitrophic interactions in a spatial
      context. We quantify the effect of bitrophic interactions on the diversity of
      plants and their animal interactors, and we show their complex dependence on the
      structure of the interaction network, the strength of interactions, and the
      dispersal rate. We then develop a method to parameterize our model with real
      world networks and apply it to 54 datasets describing three types of
      interactions: pollination, fungal association, and insect herbivory. In all three
      network types, bitrophic interactions generally lead to an increase of plant and
      animal spatial heterogeneity by decreasing local species richness while
      increasing beta-diversity.

PMID- 22393007
TI  - Evolutionary dynamics of Staphylococcus aureus during progression from carriage
      to disease.
AB  - Whole-genome sequencing offers new insights into the evolution of bacterial
      pathogens and the etiology of bacterial disease. Staphylococcus aureus is a major
      cause of bacteria-associated mortality and invasive disease and is carried
      asymptomatically by 27% of adults. Eighty percent of bacteremias match the
      carried strain. However, the role of evolutionary change in the pathogen during
      the progression from carriage to disease is incompletely understood. Here we use
      high-throughput genome sequencing to discover the genetic changes that accompany
      the transition from nasal carriage to fatal bloodstream infection in an
      individual colonized with methicillin-sensitive S. aureus. We found a single,
      cohesive population exhibiting a repertoire of 30 single-nucleotide polymorphisms
      and four insertion/deletion variants. Mutations accumulated at a steady rate over
      a 13-mo period, except for a cluster of mutations preceding the transition to
      disease. Although bloodstream bacteria differed by just eight mutations from the
      original nasally carried bacteria, half of those mutations caused truncation of
      proteins, including a premature stop codon in an AraC-family transcriptional
      regulator that has been implicated in pathogenicity. Comparison with evolution in
      two asymptomatic carriers supported the conclusion that clusters of protein
      truncating mutations are highly unusual. Our results demonstrate that bacterial
      diversity in vivo is limited but nonetheless detectable by whole-genome
      sequencing, enabling the study of evolutionary dynamics within the host.
      Regulatory or structural changes that occur during carriage may be functionally
      important for pathogenesis; therefore identifying those changes is a crucial step
      in understanding the biological causes of invasive bacterial disease.

PMID- 22393008
TI  - F1Fo-ATPase, F-type proton-translocating ATPase, at the plasma membrane is
      critical for efficient influenza virus budding.
AB  - The identification of host factors involved in virus replication is important to
      understand virus life cycles better. Accordingly, we sought host factors that
      interact with the influenza viral nonstructural protein 2 by using
      coimmunoprecipitation followed by mass spectrometry. Among proteins associating
      with nonstructural protein 2, we focused on the beta subunit of the F1Fo-ATPase,
      which received a high probability score in our mass spectrometry analysis. The
      siRNA-mediated down-regulation of the beta subunit of the F1Fo-ATPase reduced
      influenza virion formation and virus growth in cell culture. We further found
      that efficient influenza virion formation requires the ATPase activity of F1Fo
      ATPase and that plasma membrane-associated, but not mitochondrial, F1Fo-ATPase is
      important for influenza virion formation and budding. Hence, our data identify
      plasma membrane-associated F1Fo-ATPase as a critical host factor for efficient
      influenza virus replication.

PMID- 22393009
TI  - Population bulk segregant mapping uncovers resistance mutations and the mode of
      action of a chitin synthesis inhibitor in arthropods.
AB  - Because of its importance to the arthropod exoskeleton, chitin biogenesis is an
      attractive target for pest control. This point is demonstrated by the
      economically important benzoylurea compounds that are in wide use as highly
      specific agents to control insect populations. Nevertheless, the target sites of
      compounds that inhibit chitin biogenesis have remained elusive, likely preventing
      the full exploitation of the underlying mode of action in pest management. Here,
      we show that the acaricide etoxazole inhibits chitin biogenesis in Tetranychus
      urticae (the two-spotted spider mite), an economically important pest. We then
      developed a population-level bulk segregant mapping method, based on high
      throughput genome sequencing, to identify a locus for monogenic, recessive
      resistance to etoxazole in a field-collected population. As supported by
      additional genetic studies, including sequencing across multiple resistant
      strains and genetic complementation tests, we associated a nonsynonymous mutation
      in the major T. urticae chitin synthase (CHS1) with resistance. The change is in
      a C-terminal transmembrane domain of CHS1 in a highly conserved region that may
      serve a noncatalytic but essential function. Our finding of a target-site
      resistance mutation in CHS1 shows that at least one highly specific chitin
      biosynthesis inhibitor acts directly to inhibit chitin synthase. Our work also
      raises the possibility that other chitin biogenesis inhibitors, such as the
      benzoylurea compounds, may also act by inhibition of chitin synthases. More
      generally, our genetic mapping approach should be powerful for high-resolution
      mapping of simple traits (resistance or otherwise) in arthropods.

PMID- 22393010
TI  - Agonist binding evokes extensive conformational changes in the extracellular
      domain of the ATP-gated human P2X1 receptor ion channel.
AB  - P2X receptors for ATP have a wide range of physiological roles and comprise a
      structurally distinct family of ligand-gated trimeric ion channels. The crystal
      structure of a P2X4 receptor, in combination with mutagenesis studies, has
      provided a model of the intersubunit ATP-binding sites and identified an
      extracellular lateral portal, adjacent to the membrane, that funnels ions to the
      channel pore. However, little is known about the extent of ATP-induced
      conformational changes in the extracellular domain of the receptor. To address
      this issue, we have used MTSEA-biotinylation (N-Biotinoylaminoethyl
      methanethiosulfonate) to show ATP-sensitive accessibility of cysteine mutants at
      the human P2X1 receptor. Mapping these data to a P2X1 receptor homology model
      identifies significant conformational rearrangement. Electron microscopy of
      purified P2X1 receptors showed marked changes in structure on ATP binding, and
      introducing disulphide bonds between adjacent subunits to restrict intersubunit
      movements inhibited channel function. These results are consistent with agonist
      induced rotation of the propeller-head domain of the receptor, sliding of
      adjacent subunits leading to restricted access to the upper vestibule, movement
      in the ion conducting lateral portals, and gating of the channel pore.

PMID- 22393011
TI  - Temporally tuned neuronal differentiation supports the functional remodeling of a
      neuronal network in Drosophila.
AB  - During insect metamorphosis, neuronal networks undergo extensive remodeling by
      restructuring their connectivity and recruiting newborn neurons from
      postembryonic lineages. The neuronal network that directs the essential behavior,
      ecdysis, generates a distinct behavioral sequence at each developmental
      transition. Larval ecdysis replaces the cuticle between larval stages, and pupal
      ecdysis externalizes and expands the head and appendages to their adult position.
      However, the network changes that support these differences are unknown.
      Crustacean cardioactive peptide (CCAP) neurons and the peptide hormones they
      secrete are critical for ecdysis; their targeted ablation alters larval ecdysis
      progression and results in a failure of pupal ecdysis. In this study, we
      demonstrate that the CCAP neuron network is remodeled immediately before pupal
      ecdysis by the emergence of 12 late CCAP neurons. All 12 are CCAP efferents that
      exit the central nervous system. Importantly, these late CCAP neurons were found
      to be entirely sufficient for wild-type pupal ecdysis, even after targeted
      ablation of all other 42 CCAP neurons. Our evidence indicates that late CCAP
      neurons are derived from early, likely embryonic, lineages. However, they do not
      differentiate to express their peptide hormone battery, nor do they project an
      axon via lateral nerve trunks until pupariation, both of which are believed to be
      critical for the function of CCAP efferent neurons in ecdysis. Further analysis
      implicated ecdysone signaling via ecdysone receptors A/B1 and the nuclear
      receptor ftz-f1 as the differentiation trigger. These results demonstrate the
      utility of temporally tuned neuronal differentiation as a hard-wired
      developmental mechanism to remodel a neuronal network to generate a scheduled
      change in behavior.

PMID- 22393012
TI  - Improvement of islet function in a bioartificial pancreas by enhanced oxygen
      supply and growth hormone releasing hormone agonist.
AB  - Islet transplantation is a feasible therapeutic alternative for metabolically
      labile patients with type 1 diabetes. The primary therapeutic target is stable
      glycemic control and prevention of complications associated with diabetes by
      reconstitution of endogenous insulin secretion. However, critical shortage of
      donor organs, gradual loss in graft function over time, and chronic need for
      immunosuppression limit the indication for islet transplantation to a small group
      of patients. Here we present a promising approach to address these limitations by
      utilization of a macrochamber specially engineered for islet transplantation. The
      s.c. implantable device allows for controlled and adequate oxygen supply and
      provides immunological protection of donor islets against the host immune system.
      The minimally invasive implantable chamber normalized blood glucose in
      streptozotocin-induced diabetic rodents for up to 3 mo. Sufficient graft function
      depended on oxygen supply. Pretreatment with the growth hormone-releasing hormone
      (GHRH) agonist, JI-36, significantly enhanced graft function by improving glucose
      tolerance and increasing beta-cell insulin reserve in rats thereby allowing for a
      reduction of the islet mass required for metabolic control. As a result of
      hypervascularization of the tissue surrounding the device, no relevant delay in
      insulin response to glucose changes has been observed. Consequently, this system
      opens up a fundamental strategy for therapy of diabetes and may provide a
      promising avenue for future approaches to xenotransplantation.

PMID- 22393013
TI  - Lateral prefrontal cortex contributes to maladaptive decisions.
AB  - Humans consistently make suboptimal decisions involving random events, yet the
      underlying neural mechanisms remain elusive. Using functional MRI and a matching
      pennies game that captured subjects' increasing tendency to predict the break of
      a streak as it continued [i.e., the "gambler's fallacy" (GF)], we found that a
      strong blood oxygen level-dependent response in the left lateral prefrontal
      cortex (LPFC) to the current outcome preceded the use of the GF strategy 10 s
      later. Furthermore, anodal transcranial direct current stimulation over the left
      LPFC, which enhances neuronal firing rates and cerebral excitability, increased
      the use of the GF strategy, and made the decisions more "sticky." These results
      reveal a causal role of the LPFC in implementing suboptimal decision strategy
      guided by false world models, especially when such strategy requires great
      resources for cognitive control.

PMID- 22393014
TI  - Dysmyelination not demyelination causes neurological symptoms in preweaned mice
      in a murine model of Cockayne syndrome.
AB  - Cockayne syndrome (CS) is a rare autosomal recessive neurodegenerative disease
      that is associated with mutations in either of two transcription-coupled DNA
      repair genes, CSA or CSB. Mice with a targeted mutation in the Csb gene (Cs
      b(m/m)) exhibit a milder phenotype compared with human patients with mutations in
      the orthologous CSB gene. Mice mutated in Csb were crossed with mice lacking Xpc
      (Xp-c(-/-)), the global genome repair gene, to enhance the pathological symptoms.
      These Cs-b(m/m).Xp-c(-/-) mice were normal at birth but exhibited progressive
      failure to thrive, whole-body wasting, and ataxia and died at approximately
      postnatal day 21. Characterization of Cs-b(m/m).Xp-c(-/-) brains at postnatal
      stages demonstrated widespread reduction of myelin basic protein (MBP) and myelin
      in the sensorimotor cortex, the stratum radiatum, the corpus callosum, and the
      anterior commissure. Quantification of individual axons by electron microscopy
      showed a reduction in both the number of myelinated axons and the average
      diameter of myelin surrounding the axons. There were no significant differences
      in proliferation or oligodendrocyte differentiation between Cs-b(m/m).Xp-c(-/-)
      and Cs-b(m/+).Xp-c(-/-) mice. Rather, Cs-b(m/m).Xp-c(-/-) oligodendrocytes were
      unable to generate sufficient MBP or to maintain the proper myelination during
      early development. Csb is a multifunctional protein regulating both repair and
      the transcriptional response to reactive oxygen through its interaction with
      histone acetylase p300 and the hypoxia-inducible factor (HIF)1 pathway. On the
      basis of our results, combined with that of others, we suggest that in Csb the
      transcriptional response predominates during early development, whereas a
      neurodegenerative response associated with repair deficits predominates in later
      life.

PMID- 22393016
TI  - Earliest Carboniferous tetrapod and arthropod faunas from Scotland populate
      Romer's Gap.
AB  - Devonian tetrapods (limbed vertebrates), known from an increasingly large number
      of localities, have been shown to be mainly aquatic with many primitive features.
      In contrast, the post-Devonian record is marked by an Early Mississippian
      temporal gap ranging from the earliest Carboniferous (Tournaisian and early
      Visean) to the mid-Visean. By the mid-Visean, tetrapods had become effectively
      terrestrial as attested by the presence of stem amniotes, developed an
      essentially modern aspect, and given rise to the crown group. Up to now, only two
      localities have yielded tetrapod specimens from the Tournaisian stage: one in
      Scotland with a single articulated skeleton and one in Nova Scotia with isolated
      bones, many of uncertain identity. We announce a series of discoveries of
      Tournaisian-age localities in Scotland that have yielded a wealth of new tetrapod
      and arthropod fossils. These include both terrestrial and aquatic forms and new
      taxa. We conclude that the gap in the fossil record has been an artifact of
      collection failure.

PMID- 22393015
TI  - Silencing of parathyroid hormone (PTH) receptor 1 in T cells blunts the bone
      anabolic activity of PTH.
AB  - Intermittent parathyroid hormone (iPTH) treatment stimulates T-cell production of
      the osteogenic Wnt ligand Wnt10b, a factor required for iPTH to activate Wnt
      signaling in osteoblasts and stimulate bone formation. However, it is unknown
      whether iPTH induces Wnt10b production and bone anabolism through direct
      activation of the parathyroid hormone (PTH)/PTH-related protein receptor (PPR) in
      T cells. Here, we show that conditional silencing of PPR in T cells blunts the
      capacity of iPTH to induce T-cell production of Wnt10b; activate Wnt signaling in
      osteoblasts; expand the osteoblastic pool; and increase bone turnover, bone
      mineral density, and trabecular bone volume. These findings demonstrate that
      direct PPR signaling in T cells plays an important role in PTH-induced bone
      anabolism by promoting T-cell production of Wnt10b and suggest that T cells may
      provide pharmacological targets for bone anabolism.

PMID- 22393017
TI  - Mesoamerican origin of the common bean (Phaseolus vulgaris L.) is revealed by
      sequence data.
AB  - Knowledge about the origins and evolution of crop species represents an important
      prerequisite for efficient conservation and use of existing plant materials. This
      study was designed to solve the ongoing debate on the origins of the common bean
      by investigating the nucleotide diversity at five gene loci of a large sample
      that represents the entire geographical distribution of the wild forms of this
      species. Our data clearly indicate a Mesoamerican origin of the common bean. They
      also strongly support the occurrence of a bottleneck during the formation of the
      Andean gene pool that predates the domestication, which was suggested by recent
      studies based on multilocus molecular markers. Furthermore, a remarkable result
      was the genetic structure that was seen for the Mesoamerican accessions, with the
      identification of four different genetic groups that have different relationships
      with the sets of wild accessions from the Andes and northern Peru-Ecuador. This
      finding implies that both of the gene pools from South America originated through
      different migration events from the Mesoamerican populations that were
      characteristic of central Mexico.

PMID- 22393018
TI  - Molecular basis for complement recognition by integrin alphaXbeta2.
AB  - Integrin alpha(X)beta(2) functions as complement receptor for iC3b and mediates
      recognition and phagocytosis of pathogens. We used negative-stain EM to examine
      the alpha(X)beta(2) interaction with iC3b. EM class averages of alpha(X)beta(2)
      in complex with iC3b define the binding sites on both the integrin and iC3b. iC3b
      contains C3c and thioester domain moieties linked by a long flexible linker. The
      binding site is on the key ring of the C3c moiety, at the interface between the
      MG3 and MG4 domains. Similar complexes are seen between alpha(X)beta(2) and the
      C3c fragment. alpha(X)beta(2) binds through the alpha(X) alphaI domain, on the
      face known to bear the metal ion-dependent adhesion site, at the opposite end of
      the alphaI domain from its site of insertion in the beta-propeller domain.

PMID- 22393019
TI  - Salience network integrity predicts default mode network function after traumatic
      brain injury.
AB  - Efficient behavior involves the coordinated activity of large-scale brain
      networks, but the way in which these networks interact is uncertain. One theory
      is that the salience network (SN)--which includes the anterior cingulate cortex,
      presupplementary motor area, and anterior insulae--regulates dynamic changes in
      other networks. If this is the case, then damage to the structural connectivity
      of the SN should disrupt the regulation of associated networks. To investigate
      this hypothesis, we studied a group of 57 patients with cognitive impairments
      following traumatic brain injury (TBI) and 25 control subjects using the stop
      signal task. The pattern of brain activity associated with stop-signal task
      performance was studied by using functional MRI, and the structural integrity of
      network connections was quantified by using diffusion tensor imaging. Efficient
      inhibitory control was associated with rapid deactivation within parts of the
      default mode network (DMN), including the precuneus and posterior cingulate
      cortex. TBI patients showed a failure of DMN deactivation, which was associated
      with an impairment of inhibitory control. TBI frequently results in traumatic
      axonal injury, which can disconnect brain networks by damaging white matter
      tracts. The abnormality of DMN function was specifically predicted by the amount
      of white matter damage in the SN tract connecting the right anterior insulae to
      the presupplementary motor area and dorsal anterior cingulate cortex. The results
      provide evidence that structural integrity of the SN is necessary for the
      efficient regulation of activity in the DMN, and that a failure of this
      regulation leads to inefficient cognitive control.

PMID- 22393020
TI  - Actin-dependent rapid recruitment of reluctant synaptic vesicles into a fast
      releasing vesicle pool.
AB  - Glutamatergic synaptic terminals harbor reluctant synaptic vesicles (SVs) that
      contribute little to synchronous release during action potentials but are release
      competent when stimulated by sucrose or by direct intracellular application of
      calcium. It has been noted that the proximity of a release-competent SV to the
      calcium source is one of the primary factors that differentiate reluctant SVs
      from fast-releasing ones at the calyx of Held synapse. It has not been known
      whether reluctant SVs can be converted into fast-releasing ones. Here we show
      that reluctant SVs are recruited rapidly in an actin-dependent manner to become
      fast-releasing SVs once the pool of fast-releasing SVs is depleted by a short
      depolarization. Recovery of the pool of fast-releasing SVs was accompanied by a
      parallel reduction in the number of reluctant SVs. Quantitative analysis of the
      time course of depletion of fast-releasing SVs during high-frequency stimulation
      revealed that in the early phase of stimulation reluctant SVs are converted
      rapidly into fast-releasing ones, thereby counteracting short-term depression.
      During the late phase, however, after reluctant vesicles have been used up,
      another process of calmodulin-dependent recruitment of fast-releasing SVs is
      activated. These results document that reluctant SVs have a role in short-term
      plasticity and support the hypothesis of positional priming, which posits that
      reluctant vesicles are converted into fast-releasing ones via relocation closer
      to Ca(2+)-channels.

PMID- 22393021
TI  - RelA protein stimulates the activity of RyhB small RNA by acting on RNA-binding
      protein Hfq.
AB  - The conserved RNA-binding protein Hfq and its associated small regulatory RNAs
      (sRNAs) are increasingly recognized as the players of a large network of
      posttranscriptional control of gene expression in Gram-negative bacteria. The
      role of Hfq in this network is to facilitate base pairing between sRNAs and their
      trans-encoded target mRNAs. Although the number of known sRNA-mRNA interactions
      has grown steadily, cellular factors that influence Hfq, the mediator of these
      interactions, have remained unknown. We report that RelA, a protein long known as
      the central regulator of the bacterial-stringent response, acts on Hfq and
      thereby affects the physiological activity of RyhB sRNA as a regulator of iron
      homeostasis. RyhB requires RelA in vivo to arrest growth during iron depletion
      and to down-regulate a subset of its target mRNAs (fdoG, nuoA, and sodA), whereas
      the sodB and sdhC targets are barely affected by RelA. In vitro studies with
      recombinant proteins show that RelA enhances multimerization of Hfq monomers and
      stimulates Hfq binding of RyhB and other sRNAs. Hfq from polysomes extracted from
      wild-type cells binds RyhB in vitro, whereas Hfq from polysomes of a relA mutant
      strain shows no binding. We propose that, by increasing the level of the
      hexameric form of Hfq, RelA enables binding of RNAs whose affinity for Hfq is
      low. Our results suggest that, under specific conditions and/or environments, Hfq
      concentrations are limiting for RNA binding, which thereby provides an
      opportunity for cellular proteins such as RelA to impact sRNA-mediated responses
      by modulating the activity of Hfq.

PMID- 22393022
TI  - Root gravitropism is regulated by a transient lateral auxin gradient controlled
      by a tipping-point mechanism.
AB  - Gravity profoundly influences plant growth and development. Plants respond to
      changes in orientation by using gravitropic responses to modify their growth.
      Cholodny and Went hypothesized over 80 years ago that plants bend in response to
      a gravity stimulus by generating a lateral gradient of a growth regulator at an
      organ's apex, later found to be auxin. Auxin regulates root growth by targeting
      Aux/IAA repressor proteins for degradation. We used an Aux/IAA-based reporter,
      domain II (DII)-VENUS, in conjunction with a mathematical model to quantify auxin
      redistribution following a gravity stimulus. Our multidisciplinary approach
      revealed that auxin is rapidly redistributed to the lower side of the root within
      minutes of a 90 degrees  gravity stimulus. Unexpectedly, auxin asymmetry was
      rapidly lost as bending root tips reached an angle of 40 degrees  to the
      horizontal. We hypothesize roots use a "tipping point" mechanism that operates to
      reverse the asymmetric auxin flow at the midpoint of root bending. These
      mechanistic insights illustrate the scientific value of developing quantitative
      reporters such as DII-VENUS in conjunction with parameterized mathematical models
      to provide high-resolution kinetics of hormone redistribution.

PMID- 22393025
TI  - A mysterious stroke in a colon cancer patient.

PMID- 22393023
TI  - A requirement for the neuromodulators octopamine and tyramine in Drosophila
      melanogaster female sperm storage.
AB  - Female sperm storage is common among organisms with internal fertilization. It is
      important for extended fertility and, in cases of multiple mating, for sperm
      competition. The physiological mechanisms by which females store and manage
      stored sperm are poorly understood. Here, we report that the biogenic amines
      tyramine (TA) and octopamine (OA) in Drosophila melanogaster females play
      essential roles in sperm storage. D. melanogaster females store sperm in two
      types of organs, a single seminal receptacle and a pair of spermathecae. We
      examined sperm storage parameters in females mutant in enzymes required for the
      biochemical synthesis of tyrosine to TA and TA to OA, respectively. Postmating
      uterine conformational changes, which are associated with sperm entry and
      accumulation into storage, were unaffected by the absence of either TA or OA.
      However, sperm release from storage requires both TA and OA; sperm were retained
      in storage in both types of mutant females at significantly higher levels than in
      control flies. Absence of OA inhibited sperm depletion only from the seminal
      receptacle, whereas absence of both OA and TA perturbed sperm depletion from both
      storage organ types. We find innervation of the seminal receptacle and
      spermathecae by octopaminergic-tyraminergic neurons. These findings identify a
      distinct role for TA and OA in reproduction, regulating the release of sperm from
      storage, and suggest a mechanism by which Drosophila females actively regulate
      the release of stored sperm.

PMID- 22393024
TI  - Injury-independent induction of reactive gliosis in retina by loss of function of
      the LIM homeodomain transcription factor Lhx2.
AB  - Muller glia are the primary glial subtype in the retina and perform a wide range
      of physiological tasks in support of retinal function, but little is known about
      the transcriptional network that maintains these cells in their differentiated
      state. We report that selective deletion of the LIM homeodomain transcription
      factor Lhx2 from mature Muller glia leads to the induction of reactive retinal
      gliosis in the absence of injury. Furthermore, Lhx2 expression is also down
      regulated in Prph2(Rd2/Rd2) animals immediately before the onset of reactive
      gliosis. Analysis of conditional Lhx2 knockouts showed that gliosis was
      hypertrophic but not proliferative. Aging of experimental animals demonstrated
      that constitutive reactive gliosis induced by deletion of Lhx2 reduced rates of
      ongoing apoptosis and compromised both rod and cone photoreceptor function.
      Additionally, these animals showed a dramatically reduced ability to induce
      expression of secreted neuroprotective factors and displayed enhanced rates of
      apoptosis in light-damage assays. We provide in vivo evidence that Lhx2 actively
      maintains mature Muller glia in a nonreactive state, with loss of function
      initiating a specific program of nonproliferative hypertrophic gliosis.

PMID- 22393026
TI  - Dynamic expression pattern and subcellular localization of the Rhox10 homeobox
      transcription factor during early germ cell development.
AB  - Homeobox genes encode transcription factors that regulate diverse developmental
      events. The largest known homeobox gene cluster - the X-linked mouse reproductive
      homeobox (Rhox) cluster - harbors genes whose expression patterns and functions
      are largely unknown. Here, we report that a member of this cluster, Rhox10, is
      expressed in male germ cells. Rhox10 is highly transcribed in spermatogonia in
      vivo and is upregulated in response to the differentiation-inducing agent
      retinoic acid in vitro. Using a specific RHOX10 antiserum that we generated, we
      found that RHOX10 protein is selectively expressed in fetal gonocytes, germline
      stem cells, spermatogonia, and early spermatocytes. RHOX10 protein undergoes a
      dramatic shift in subcellular localization as germ cells progress from
      mitotically arrested gonocytes to mitotic spermatogonia and from mitotic
      spermatogonia to early meiotic spermatocytes, consistent with RHOX10 performing
      different functions in these stages.

PMID- 22393027
TI  - Testosterone and tusks: maturation and seasonal reproductive patterns of live,
      free-ranging male dugongs (Dugong dugon) in a subtropical population.
AB  - Knowledge of male reproductive status and activity in free-ranging animals is
      vital to understanding reproductive patterns and population dynamics. Until now,
      almost all information regarding reproductive behavior of the dugong, a cryptic
      marine mammal, has relied on post-mortem examination. We examined the
      relationships between body length, tusk eruption (secondary sexual
      characteristic), seasonality, and group association on fecal testosterone
      metabolite concentrations in 322 free-ranging dugongs (159 males, 163 females) in
      subtropical Moreton Bay, Australia. Fecal testosterone concentrations
      demonstrated biologically meaningful differences in testicular activity between
      sexes and across reproductive/age classes, and were correlated with circulating
      concentrations in serum. Male dugongs have a pre-reproductive period that
      persists until a body length of 240 cm is achieved. Puberty apparently occurs
      between 240 and 260 cm body length when fecal testosterone levels increase
      fourfold (>500 ng/g) over juvenile levels, and is associated with tusk eruption.
      However, social maturity may be delayed until male dugongs are larger than 260 cm
      with well-developed tusks. In mature males, the lowest (<500 ng/g) fecal
      testosterone concentrations occur in the austral autumn months with maximal
      concentrations in September-October, coincident with the onset of a spring mating
      season. During spring, solitary mature males had fecal testosterone
      concentrations double those of mature males sampled within groups, potentially
      suggesting a mating strategy involving roving of reproductively active males.
      This study demonstrates that single-point physiological data from individuals
      across a population have value as indicators of reproductive processes. Our
      approach provides an efficacious non-lethal method for the census of reproductive
      status and seasonality in live male dugongs.

PMID- 22393028
TI  - CS injection of tenosynovitis in patients with chronic inflammatory arthritis:
      the role of US.
AB  - OBJECTIVE: The main aim of this study was to investigate the short-term efficacy
      of CS loco-regional treatment performed under US guidance in tenosynovitis of
      patients with chronic inflammatory arthritis. METHODS: Thirty consecutive
      patients affected by chronic arthritis and with clinical suspicion of
      tenosynovitis were recruited to undergo US assessment. In the sonographically
      proven cases, US-guided CS injection was performed. A visual analogue scale for
      pain (ranging from 0 to 10) and a tenderness score (ranging from 0 to 3) were
      used for the clinical evaluation. Sonographic pathological findings indicative of
      tenosynovitis were scored using a semi-quantitative 4-grade scoring system, for
      both grey-scale and power Doppler US, at baseline and during a follow-up visit at
      2 weeks after the CS injection. RESULTS: In 21 (70%) of 30 patients, the clinical
      suspicion of tenosynovitis was confirmed (9 with RA, 11 with PsA and 1 with ReA).
      In the other nine patients, US revealed synovitis of the adjacent joints,
      bursitis, oedema of the s.c. tissue or a partial tear. In all cases the
      appropriate needle placement and subsequent CS injection into the tendon sheath
      were obtained with US confirmation. A significant reduction in all clinical and
      sonographic scorings was found during the follow-up visit. CONCLUSIONS: The
      present study shows the efficacy of US-guided peritendinous CS injections in the
      management of patients with chronic inflammatory arthritis presenting as US
      proven tenosynovitis.

PMID- 22393029
TI  - Barley-derived beta-glucans increases gut permeability, ex vivo epithelial cell
      binding to E. coli, and naive T-cell proportions in weanling pigs.
AB  - Weaning in young animals is associated with an increased incidence of
      gastrointestinal infections. beta-glucans exert numerous physiological effects,
      including altering immune function. The objective of this study was to determine
      the effects of feeding barley (Hordeum vulgare L.)-derived beta-glucans on immune
      and intestinal function in weanling pigs (Sus scrofa). Thirty-one individually
      housed Dutch Landrace pigs (21 d; initial BW, 6,298 +/- 755 g) were weaned and
      fed a wheat-based diet (control) or a low (Lo-BG), medium (Med-BG), or high beta
      glucan-containing barley-based diet (Hi-BG) for 2 wk with 7 or 8 pigs/treatment.
      Intestinal segments were analyzed for permeability using Ussing chambers and K88
      Escherichia coli adhesion to enterocytes was assessed ex vivo. Immune cells from
      mesenteric lymph nodes, peripheral blood, and Peyer's patches were analyzed for
      lymphocyte subsets by indirect immunofluorescence and the ability to respond ex
      vivo to mitogens by (3)H-thymidine incorporation. Hematology and neutrophil
      function were determined by flow cytometry. Neutrophil burst, size, and
      granularity, lymphocyte proliferation, and B-cell distribution in peripheral
      blood lymphocytes, Peyer's patches, and mesenteric lymph nodes were not affected
      by beta-glucans content of the diet. The beta-glucans content of the diet altered
      blood concentrations of erythrocytes and leukocytes, CD4, CD45RA, and CD8 blood
      cells (P < 0.05). In addition, feeding beta-glucan resulted in increased (P <
      0.05) percentage CD45RA positive cells in peripheral blood lymphocytes, Peyer's
      patches, and mesenteric lymph nodes. Mannitol permeability and tissue conductance
      were increased (P < 0.05) in Hi-BG fed pigs compared with control pigs.
      Percentage maximum K88-E.coli binding was increased in proportion to the beta
      glucan content of the diet (P < 0.05). Although beta-glucan feeding during the
      weaning period increased blood lymphocytes and the proportion of naive T-cells,
      it also increased E. coli-enterocyte binding and intestinal permeability. beta
      glucan may alter immune and intestinal function of weaning pigs.

PMID- 22393030
TI  - Evaluation of rumen fatty acid hydrogenation intermediates and differences in
      bacterial communities after feeding wheat- or corn-based dried distillers grains
      to feedlot cattle.
AB  - The effect of partially replacing rolled barley (86.6% of control diet) with 20%
      wheat dried distillers grains plus solubles (DDGS), 40% wheat DDGS, 20% corn
      DDGS, or 40% corn DDGS (dietary DM basis) on rumen fluid fatty acid (FA)
      composition and some rumen bacterial communities was evaluated using 100 steers
      (20 per treatment). Wheat DDGS increased the 11t- to 10t-18:1 ratio (P < 0.05) in
      rumen fluid and there was evidence that the conversion of trans-18:1 to 18:0 was
      reduced in the control and wheat DDGS diets but not in the corn DDGS diet.
      Bacterial community profiles obtained using denaturing gradient gel
      electrophoresis and evaluated by Pearson correlation similarity matrices were not
      consistent for diet and, therefore, these could not be linked to different
      specific rumen FA. This inconsistency may be related to the nature of diets fed
      (dominant effect of barley), limited change in dietary composition as the result
      of DDGS inclusion, large animal-to-animal variation, and possibly additional
      stress as a result of transport just before slaughter. Ruminal densities of a key
      fiber-digesting bacteria specie that produces 11t-18:1 from linoleic and
      linolenic acids (Butyrivibrio fibrisolvens), and a lactate producer originally
      thought responsible for production of 10t,12c-18:2 (Megasphaera elsdenii) were
      not influenced by diet (P > 0.05).

PMID- 22393031
TI  - Effects of nutritional plane and selenium supply during gestation on visceral
      organ mass and indices of intestinal growth and vascularity in primiparous ewes
      at parturition and during early lactation.
AB  - Objectives were to investigate effects of nutritional plane and Se supply during
      gestation on visceral organ mass and intestinal growth and vascularization in
      ewes at parturition and during early lactation. Primiparous Rambouillet ewes (n =
      84) were allocated to 2 * 3 * 2 factorial arrangement of treatments. Factors
      included dietary Se [adequate Se (ASe, 11.5 MUg/kg BW) or high Se (HSe, 77.0
      MUg/kg BW)], nutritional plane [60% (restricted; RES), 100% (control; CON), or
      140% (high; HIH)], and physiological stage at necropsy (parturition or d 20 of
      lactation). At parturition, lambs were removed and 42 ewes (7 per treatment) were
      necropsied. Remaining ewes were transitioned to a common diet which met lactation
      requirements and mechanically milked for 20 d. In the absence of interactions (P
      > 0.10), main effects are reported. At parturition, stomach complex and liver
      masses were greatest for HIH, intermediate for CON, and least for RES (P < 0.02).
      Small intestinal mass was greater (P <= 0.002) for HIH than RES and CON, and
      greater (P < 0.01) for ASe than HSe. During early lactation, RES and CON
      gastrointestinal masses increased disproportionally to BW (P < 0.05). At
      parturition, jejunal mucosal density was less (P <= 0.01) for RES than CON and
      HIH, whereas CON had greater (P < 0.003) jejunal mucosal RNA concentration and
      RNA:DNA than RES and HIH. Although there were no differences (P > 0.17) at
      parturition, jejunal cell percent proliferation was greatest in RES, intermediate
      in CON, and least in HIH (P <= 0.09) at d 20 lactation. At both stages, RES had
      less (P = 0.01) jejunal capillary area density than HIH and less (P <= 0.03)
      capillary surface density than CON and HIH. During lactation, jejunal capillary
      size was greater (P = 0.04) for ewes previously fed HSe compared with ASe. At
      parturition, ASe-HIH had greater (P < 0.02) jejunal mucosal endothelial nitric
      oxide synthase 3 mRNA than all other treatments and greater (P = 0.10) vascular
      endothelial growth factor (VEGF) than all treatments, except ASe-RES. In
      addition, CON had less (P <= 0.08) jejunal VEGF receptor-1 (FLT1) mRNA compared
      with RES and HIH, and ASe had greater (P = 0.003) FLT1 than HSe at parturition.
      Ewes fed HIH had greater (P = 0.04) jejunal VEGF receptor-2 mRNA compared with
      RES. Results indicate that maternal intestinal growth and vascularization are
      responsive to nutritional plane and dietary Se during gestation and undergo
      changes postpartum when under similar lactational management.

PMID- 22393032
TI  - Early experience with diverse foods increases intake of nonfamiliar flavors and
      feeds in sheep.
AB  - This study determined whether early experiences by sheep with monotonous or
      diverse diets influence intake of unfamiliar flavors and feeds later in life.
      Thirty 2-mo-old lambs were randomly assigned to 3 treatment diets (n = 10):
      diverse (DIV), diverse with plant toxins (DIV+T), and monotonous (MON). Lambs in
      DIV received in 9 successive periods of exposure 4-way choice combinations of 2
      foods high in energy and 2 foods high in protein from an array of 6 foods: 3 high
      in energy [beet pulp, oat grain, and a mix of milo:grape pomace (60:40)] and 3
      high in digestible protein (DP) (soybean meal, alfalfa, corn gluten meal). Lambs
      in DIV+T received the same exposure as DIV, but 2 plant toxins, oxalic acid
      (1.5%) and quebracho tannins (10%), were randomly added to 2 of the feeds in each
      of the choice combinations. Lambs in MON received a monotonous balanced diet,
      made with a mixture of all 6 feeds detailed before. All treatments received their
      feed in 4 separate buckets. During exposure, treatments did not differ in total
      daily DMI (P = 0.31), but daily intake of ME was less (P < 0.02) and daily intake
      of DP was greater (P < 0.03) for lambs in DIV and DIV+T than for lambs in MON.
      Treatments did not differ in ADG or G:F (P > 0.05). After exposure, lambs were
      offered a familiar feed (wheat bran) containing novel flavors (maple, garlic, or
      bitter) and 2-way choices of novel feeds (fescue hay vs. corn distillers grains,
      rice vs. calf manna, and green peas vs. rolled oats). Intake of maple-flavored
      wheat bran tended (P = 0.08) to be greater for lambs in DIV than for lambs in
      DIV+T and MON. Intake of bitter-flavored and garlic-flavored wheat bran were
      greater (P = 0.03 and P = 0.04, respectively) for lambs in DIV and DIV+T than for
      lambs in MON. During 2-way choice trials, lambs in DIV, but not in DIV+T, showed
      greater intakes of fescue hay (P = 0.05) and rice (P = 0.04) than lambs in MON.
      Intake of green peas was greater (P = 0.03) for lambs in DIV and DIV+T than for
      lambs in MON. At the end of testing, lambs in DIV but not in DIV+T showed greater
      ADG than lambs in MON (P = 0.05). Thus, early exposure to diverse foods enhanced
      acceptance of novel flavors relative to early exposure to a monotonous ration.
      Early experience with diverse feeds plus plant toxins led to a less diverse diet
      than early experience with diverse feeds. Early exposure to diverse feeds may be
      beneficial in production systems that require rapid acceptance and high intake of
      unfamiliar feeds.

PMID- 22393033
TI  - Effects of copper supplementation on feedlot performance, carcass
      characteristics, and rumen sulfur metabolism of growing cattle fed diets
      containing 60% dried distillers grains.
AB  - The effects of 3 supplemental Cu concentrations on feedlot performance, mineral
      absorption, carcass characteristics, and ruminal S metabolism of cattle fed diets
      containing 60% dried distillers grains with solubles (DDGS) were evaluated in 2
      experiments. Experiment 1 was conducted with 84 Angus-cross yearling steers and
      heifers (initial BW = 238 +/- 36 kg), which were blocked by gender and allocated
      to 12 pens. Supplemental dietary Cu (tribasic copper chloride) treatments were:
      1) 0 mg Cu/kg diet DM, 2) 100 mg Cu/kg diet DM, 3) 200 mg Cu/kg diet DM. The
      remainder of the diet was DDGS (60%), grass hay (10%), pelleted soy hulls (15%),
      and a vitamin-mineral supplement (15%). Diets were offered ad libitum throughout
      the finishing phase (168 d). Three cattle from each pen (n = 36) were harvested
      on d 168 and carcass data and liver samples were collected. Copper
      supplementation did not affect ADG (P = 0.22). However, the nonsignificant trend
      for increased ADG and decreased DMI led to a linear increase (P = 0.02) feed
      efficiency (G:F = 0.167, 0.177, and 0.177 for 0, 100, and 200 mg Cu/kg diet DM,
      respectively). The apparent absorption of Cu decreased quadratically (P = 0.07)
      and the apparent absorption of Mn and Zn were decreased linearly (P = 0.03 and P
      = 0.05, respectively) with increased Cu supplementation. Cattle supplemented with
      100 or 200 mg Cu/kg diet DM had greater liver Cu concentrations (P < 0.01) than
      cattle that were not supplemented with Cu. There were no treatment effects (P >
      0.10) on HCW, LM area, USDA yield grade, backfat, or marbling score. Experiment 2
      was conducted with 6 ruminally fistulated steers that were fed the same diets as
      in Exp 1 in a replicated 3 * 3 Latin Square design. Copper supplementation did
      not affect (P > 0.10) ruminal pH or liquid S(2-) concentrations in steers
      consuming 60% DDGS diets (total dietary S = 0.55%). From 3 to 9 h after feeding,
      H(2)S gas concentration was decreased in those cattle supplemented with 100 mg
      Cu/kg diet. Concentration of H(2)S gas did not differ among cattle supplemented
      with 0 or 200 mg Cu/kg diet DM on 60% DDGS diets. Supplemental Cu improved feed
      efficiency in cattle consuming diets containing 60% DDGS; however, effects of Cu
      on rumen S metabolism were minimal even when supplemented at twice the maximum
      tolerable limit for beef cattle (NRC, 2000).

PMID- 22393034
TI  - The influence of ergonomic devices on mechanical load during patient handling
      activities in nursing homes.
AB  - OBJECTIVES: Mechanical load during patient handling activities is an important
      risk factor for low back pain among nursing personnel. The aims of this study
      were to describe required and actual use of ergonomic devices during patient
      handling activities and to assess the influence of these ergonomic devices on
      mechanical load during patient handling activities. METHODS: For each patient,
      based on national guidelines, it was recorded which specific ergonomic devices
      were required during distinct patient handling activities, defined by
      transferring a patient, providing personal care, repositioning patients in the
      bed, and putting on and taking off anti-embolism stockings. During real-time
      observations over ~60 h among 186 nurses on 735 separate patient handling
      activities in 17 nursing homes, it was established whether ergonomic devices were
      actually used. Mechanical load was assessed through observations of frequency and
      duration of a flexed or rotated trunk >30 degrees  and frequency of pushing,
      pulling, lifting or carrying requiring forces <100 N, between 100 and 230 N, and
      >230 N from start to end of each separate patient handling activity. The number
      of patients and nurses per ward and the ratio of nurses per patient were used as
      ward characteristics with potential influence on mechanical load. A mixed-effect
      model for repeated measurements was used to determine the influence of ergonomic
      devices and ward characteristics on mechanical load. RESULTS: Use of ergonomic
      devices was required according to national guidelines in 520 of 735 (71%)
      separate patient handling activities, and actual use was observed in 357 of 520
      (69%) patient handling activities. A favourable ratio of nurses per patient was
      associated with a decreased duration of time spent in awkward back postures
      during handling anti-embolism stocking (43%), patient transfers (33%), and
      personal care of patients (24%) and also frequency of manually lifting patients
      (33%). Use of lifting devices was associated with a lower frequency of forces
      exerted (64%), adjustable bed and shower chairs with a shorter duration of
      awkward back postures (38%), and an anti-embolism stockings slide with a lower
      frequency of forces exerted (95%). CONCLUSIONS: In wards in nursing homes with a
      higher number of staff less awkward back postures as well as forceful lifting
      were observed during patient handling activities. The use of ergonomic devices
      was high and associated with less forceful movements and awkward back postures.
      Both aspects will most likely contribute to the prevention of low back pain among
      nurses.

PMID- 22393035
TI  - The subgenomic promoter of brome mosaic virus folds into a stem-loop structure
      capped by a pseudo-triloop that is structurally similar to the triloop of the
      genomic promoter.
AB  - In brome mosaic virus, both the replication of the genomic (+)-RNA strands and
      the transcription of the subgenomic RNA are carried out by the viral replicase.
      The production of (-)-RNA strands is dependent on the formation of an AUA triloop
      in the stem-loop C (SLC) hairpin in the 3'-untranslated region of the (+)-RNA
      strands. Two alternate hypotheses have been put forward for the mechanism of
      subgenomic RNA transcription. One posits that transcription commences by
      recognition of at least four key nucleotides in the subgenomic promoter by the
      replicase. The other posits that subgenomic transcription starts by binding of
      the replicase to a hairpin formed by the subgenomic promoter that resembles the
      minus strand promoter hairpin SLC. In this study, we have determined the three
      dimensional structure of the subgenomic promoter hairpin using NMR spectroscopy.
      The data show that the hairpin is stable at 30 degrees C and that it forms a
      pseudo-triloop structure with a transloop base pair and a nucleotide completely
      excluded from the helix. The transloop base pair is capped by an AUA triloop that
      possesses an extremely well packed structure very similar to that of the AUA
      triloop of SLC, including the formation of a so-called clamped-adenine motif. The
      similarities of the NMR structures of the hairpins required for genomic RNA and
      subgenomic RNA synthesis show that the replicase recognizes structure rather than
      sequence-specific motifs in both promoters.

PMID- 22393037
TI  - Sign of the times.

PMID- 22393038
TI  - A glance to the future.

PMID- 22393039
TI  - Commentary on: Ninety minutes and longer: single dose myocardial protection
      technique utilizing the Del Nido cardioplegia solution for myocardial protection
      during congenital heart surgery procedures.

PMID- 22393036
TI  - Guidelines for improving entry into and retention in care and antiretroviral
      adherence for persons with HIV: evidence-based recommendations from an
      International Association of Physicians in AIDS Care panel.
AB  - DESCRIPTION: After HIV diagnosis, timely entry into HIV medical care and
      retention in that care are essential to the provision of effective antiretroviral
      therapy (ART). Adherence to ART is among the key determinants of successful HIV
      treatment outcome and is essential to minimize the emergence of drug resistance.
      The International Association of Physicians in AIDS Care convened a panel to
      develop evidence-based recommendations to optimize entry into and retention in
      care and ART adherence for people with HIV. METHODS: A systematic literature
      search was conducted to produce an evidence base restricted to randomized,
      controlled trials and observational studies with comparators that had at least 1
      measured biological or behavioral end point. A total of 325 studies met the
      criteria. Two reviewers independently extracted and coded data from each study
      using a standardized data extraction form. Panel members drafted recommendations
      based on the body of evidence for each method or intervention and then graded the
      overall quality of the body of evidence and the strength for each recommendation.
      RECOMMENDATIONS: Recommendations are provided for monitoring entry into and
      retention in care, interventions to improve entry and retention, and monitoring
      of and interventions to improve ART adherence. Recommendations cover ART
      strategies, adherence tools, education and counseling, and health system and
      service delivery interventions. In addition, they cover specific issues
      pertaining to pregnant women, incarcerated individuals, homeless and marginally
      housed individuals, and children and adolescents, as well as substance use and
      mental health disorders. Recommendations for future research in all areas are
      also provided.

PMID- 22393040
TI  - Human cathepsin V protease participates in production of enkephalin and NPY
      neuropeptide neurotransmitters.
AB  - Proteases are required for processing precursors into active neuropeptides that
      function as neurotransmitters for cell-cell communication. This study
      demonstrates the novel function of human cathepsin V protease for producing the
      neuropeptides enkephalin and neuropeptide Y (NPY). Cathepsin V is a human
      specific cysteine protease gene. Findings here show that expression of cathepsin
      V in neuroendocrine PC12 cells and human neuronal SK-N-MC cells results in
      production of (Met)enkephalin from proenkephalin. Gene silencing of cathepsin V
      by siRNA in human SK-N-MC cells results in reduction of (Met)enkephalin by more
      than 80%, illustrating the prominent role of cathepsin V for neuropeptide
      production. In vitro processing of proenkephalin by cathepsin V occurs at dibasic
      residue sites to generate enkephalin-containing peptides and an ~24-kDa
      intermediate present in human brain. Cathepsin V is present in human brain cortex
      and hippocampus where enkephalin and NPY are produced and is present in purified
      human neuropeptide secretory vesicles. Colocalization of cathepsin V with
      enkephalin and NPY in secretory vesicles of human neuroblastoma cells was
      illustrated by confocal microscopy. Furthermore, expression of cathepsin V with
      proNPY results in NPY production. These findings indicate the unique function of
      human cathepsin V for producing enkephalin and NPY neuropeptides required for
      neurotransmission in health and neurological diseases.

PMID- 22393041
TI  - Protein kinase C delta (PKCdelta)-extracellular signal-regulated kinase 1/2
      (ERK1/2) signaling cascade regulates glycogen synthase kinase-3 (GSK-3)
      inhibition-mediated interleukin-10 (IL-10) expression in lipopolysaccharide (LPS)
      induced endotoxemia.
AB  - Glycogen synthase kinase-3 (GSK-3) modulates a wide array of cellular processes,
      including embryonic development, cell differentiation, survival, and apoptosis.
      Recently, it was reported that a GSK-3 inhibitor attenuates lipopolysaccharide
      (LPS)-induced septic shock and regulates the mortality of endotoxemic mice.
      However, the detailed mechanism of reduced mortality via GSK-3 inhibition is not
      well defined. Herein, we showed that GSK-3 inhibition induces extracellular
      signal-regulated kinase 1/2 (ERK1/2) activation under LPS-stressed conditions via
      protein kinase C delta (PKCdelta) activation. Furthermore, PKCdelta-induced
      ERK1/2 activation by the inhibition of GSK-3 provoked the production of
      interleukin (IL)-10, playing a crucial role in regulating endotoxemia. Using a
      mitogen-activated protein kinase kinase-1 (MEK-1) and PKCdelta inhibitor, we
      confirmed that GSK-3 inhibition induces PKCdelta and subsequent ERK1/2
      activation, resulting in increased IL-10 expression under LPS-treated conditions.
      We verified that septic shock caused by LPS is attenuated by GSK-3 inhibition
      using a GSK-3 inhibitor. This relieved endotoxemia induced by GSK-3 inhibition
      was restored in an ERK1/2-dependent manner. Taken together, IL-10 expression
      produced by GSK-3 inhibition-induced ERK1/2 activation via PKCdelta relieved LPS
      mediated endotoxemia. This finding suggests that IL-10 hyperexpression resulting
      from GSK-3 inhibition-induced ERK activation could be a new therapeutic pathway
      for endotoxemia.

PMID- 22393042
TI  - Epigenetic regulation of tumor necrosis factor alpha (TNFalpha) release in human
      macrophages by HIV-1 single-stranded RNA (ssRNA) is dependent on TLR8 signaling.
AB  - Human macrophages at mucosal sites are essential targets for acute HIV infection.
      During the chronic phase of infection, they are persistent reservoirs for the
      AIDS virus. HIV virions gain entry into macrophages following ligation of surface
      CD4-CCR5 co-receptors, which leads to the release of two copies of HIV ssRNA.
      These events lead to reverse transcription and viral replication initiation. Toll
      like receptors TLR7 and TLR8 recognize specific intracellular viral ssRNA
      sequences, but in human alveolar macrophages, their individual roles in TLR
      mediated HIV ssRNA recognition are unclear. In the current study, HIV-1 ssRNA
      induced TNFalpha release in a dose-dependent manner in adherent human macrophages
      expressing both intracellular TLR7 and TLR8. This response was reduced by
      inhibiting either endocytosis (50 MUm dynasore) or endosomal acidification (1
      MUg/ml chloroquine). Either MYD88 or TLR8 gene knockdown with relevant siRNA
      reduced HIV-1 ssRNA-mediated TNFalpha release, but silencing TLR7 had no effect
      on this response. Furthermore, HIV-1 ssRNA induced histone 4 acetylation at the
      TNFalpha promoter as well as trimethylation of histone 3 at lysine 4, whereas
      TLR8 gene knockdown reduced these effects. Taken together in human macrophages,
      TLR8 binds and internalizes HIV ssRNA, leading to endosomal acidification,
      chromatin remodeling, and increases in TNFalpha release. Drugs targeting
      macrophage TLR8-linked signaling pathways may modulate the innate immune response
      to acute HIV infection by reducing viral replication.

PMID- 22393043
TI  - IcmF family protein TssM exhibits ATPase activity and energizes type VI
      secretion.
AB  - The type VI secretion system (T6SS) with diversified functions is widely
      distributed in pathogenic Proteobacteria. The IcmF (intracellular multiplication
      protein F) family protein TssM is a conserved T6SS inner membrane protein.
      Despite the conservation of its Walker A nucleotide-binding motif, the NTPase
      activity of TssM and its role in T6SS remain obscure. In this study, we
      characterized TssM in the plant pathogen Agrobacterium tumefaciens and provided
      the first biochemical evidence for TssM exhibiting ATPase activity to power the
      secretion of the T6SS hallmark protein, hemolysin-coregulated protein (Hcp).
      Amino acid substitutions in the Walker A motif of TssM caused reduced ATP binding
      and hydrolysis activity. Importantly, we discovered the Walker B motif of TssM
      and demonstrated that it is critical for ATP hydrolysis activity. Protein-protein
      interaction studies and protease susceptibility assays indicated that TssM
      undergoes an ATP binding-induced conformational change and that subsequent ATP
      hydrolysis is crucial for recruiting Hcp to interact with the periplasmic domain
      of the TssM-interacting protein TssL (an IcmH/DotU family protein) into a ternary
      complex and mediating Hcp secretion. Our findings strongly argue that TssM
      functions as a T6SS energizer to recruit Hcp into the TssM-TssL inner membrane
      complex prior to Hcp secretion across the outer membrane.

PMID- 22393045
TI  - MiR-3120 is a mirror microRNA that targets heat shock cognate protein 70 and
      auxilin messenger RNAs and regulates clathrin vesicle uncoating.
AB  - We show that a single gene locus gives rise to two fully processed and functional
      miRNAs, i.e. that due to imperfect base pairing, two distinct microRNAs (miRNAs)
      can be produced from the fully complementary DNA strands. The antisense strand
      encodes miR-214, which is transcribed by its own promoter, whereas a novel miRNA,
      miR-3120, is co-expressed with its host gene mRNA. We also found that miR-3120
      regulates important aspects of cellular function that are similar to that of its
      host gene, dynamin-3. miR-3120 was found to be located in neuronal cell bodies
      and to target Hsc70 and auxilin, and its lentivirus-mediated expression inhibited
      the uncoating of clathrin-coated vesicles. Finally, mirror miRNAs are likely to
      represent a new group of miRNAs with complex roles in coordinating gene
      expression.

PMID- 22393044
TI  - Phospholipase A2IValpha regulates phagocytosis independent of its enzymatic
      activity.
AB  - Group IValpha phospholipase A(2) (PLA(2)IValpha) is a lipolytic enzyme that
      catalyzes the hydrolysis of membrane phospholipids to generate precursors of
      potent inflammatory lipid mediators. Here, the role of PLA(2)IValpha in Fc
      receptor (FcR)-mediated phagocytosis was investigated, demonstrating that
      PLA(2)IValpha is selectively activated upon FcR-mediated phagocytosis in
      macrophages and that it rapidly translocates to the site of the nascent
      phagosome. Moreover, pharmacological inhibition of PLA(2)IValpha by pyrrophenone
      reduces particle internalization by up to 50%. In parallel, fibroblasts from
      PLA(2)IValpha knock-out mice overexpressing FcgammaRIIA and able to internalize
      IgG-opsonized beads show 50% lower phagocytosis, compared with wild-type cells,
      and transfection of PLA(2)IValpha fully recovers this impaired function.
      Interestingly, transfection of the catalytically inactive deleted PLA(2)IValpha
      mutant (PLA(2)IValpha(1-525)) and point mutant (PLA(2)IValpha-S228C) also
      promotes recovery of this impaired function. Finally, transfection of the
      PLA(2)IValpha C2 domain (which is directly involved in PLA(2)IValpha membrane
      binding), but not of PLA(2)IValpha-D43N (which cannot bind to membranes), rescues
      FcR-mediated phagocytosis. These data unveil a new mechanism of action for
      PLA(2)IValpha, which demonstrates that the membrane binding, and not the
      enzymatic activity, is required for PLA(2)IValpha modulation of FcR-mediated
      phagocytosis.

PMID- 22393046
TI  - RhoGDI SUMOylation at Lys-138 increases its binding activity to Rho GTPase and
      its inhibiting cancer cell motility.
AB  - The Rho GDP dissociation inhibitor (RhoGDI) can bind to small GTPases and keep
      them in a biologically inactive state in cytoplasm, through which it affects
      actin polymerization and cell motility. However, mechanisms underlying how RhoGDI
      regulates Rho GTPase complex formation/membrane extraction/GTPase dissociation
      remain largely unexplored. Our previous studies reported that X-linked inhibitor
      of apoptosis protein (XIAP) interacted with RhoGDI via its RING domain and
      negatively modulated RhoGDI SUMOylation and HCT116 cancer cell migration. Here,
      we identified that RhoGDI SUMOylation specifically occurred at Lys-138, which was
      inhibited by XIAP domain. We further demonstrated that RhoGDI SUMOylation at Lys
      138 was crucial for inhibiting actin polymerization and cytoskeleton formation as
      well as cancer cell motility. Moreover, SUMO-RhoGDI had a much higher binding
      affinity to small Rho GTPase compared with the un-SUMOylated form of RhoGDI.
      Taken together, our study demonstrated a novel modification of RhoGDI,
      SUMOylation at Lys-138, which played a key role in regulating Rho GTPase
      activation in cancer cells. The physiological regulation of RhoGDI SUMOylation by
      the RING domain of XIAP may account for modulation of cancer cell invasion and
      metastasis by XIAP.

PMID- 22393047
TI  - Protective role of estrogen-induced miRNA-29 expression in carbon tetrachloride
      induced mouse liver injury.
AB  - Previous studies have indicated that female animals are more resistant to carbon
      tetrachloride (CCl(4))-induced liver fibrosis than male animals, and that
      estradiol (E(2)) treatment can inhibit CCl(4)-induced animal hepatic fibrosis.
      The underlying mechanism governing these phenomena, however, has not been fully
      elucidated. Here we reported the role of estrogen-induced miRNA-29 (miR-29)
      expression in CCl(4)-induced mouse liver injury. Hepatic miR-29 levels were
      differentially regulated in female and male mice during CCl(4) treatment.
      Specifically, the levels of miR-29a and miR-29b expression were significantly
      decreased in the livers of male, but not female, mice following 4 weeks of CCl(4)
      treatment. The down-regulation of miR-29a and miR-29b in male mouse livers
      correlated with the early development of liver fibrosis, as indicated by
      increased expressions of fibrotic markers in male mice relative to female mice.
      In addition, E(2) was maintained at a higher level in female mice than in male
      mice. In contrast to TGF-beta1 that decreased miR-29a/b expression in murine
      hepatoma IAR20 cells and normal hepatocytes, E(2) enhanced the expression of miR
      29a/b through suppression of the nuclear factor-kappaB (NF-kappaB) signal
      pathway, which negatively regulates miR-29 expression. Furthermore, both E(2)
      treatment and intravenous injection of the recombinant adenovirus expressing miR
      29a/b markedly increased the miR-29a/b level and attenuated the expression of
      fibrotic markers in mouse livers during CCl(4) treatment, supporting the
      protective role of E(2)-induced miR-29 in CCl(4)-induced hepatic injury. In
      conclusion, our results collectively demonstrate that estrogen can inhibit CCl(4)
      induced hepatic injury through the induction of hepatic miR-29.

PMID- 22393048
TI  - Impact of oxidative stress on ascorbate biosynthesis in Chlamydomonas via
      regulation of the VTC2 gene encoding a GDP-L-galactose phosphorylase.
AB  - The L-galactose (Smirnoff-Wheeler) pathway represents the major route to L
      ascorbic acid (vitamin C) biosynthesis in higher plants. Arabidopsis thaliana
      VTC2 and its paralogue VTC5 function as GDP-L-galactose phosphorylases converting
      GDP-L-galactose to L-galactose-1-P, thus catalyzing the first committed step in
      the biosynthesis of L-ascorbate. Here we report that the L-galactose pathway of
      ascorbate biosynthesis described in higher plants is conserved in green algae.
      The Chlamydomonas reinhardtii genome encodes all the enzymes required for vitamin
      C biosynthesis via the L-galactose pathway. We have characterized recombinant C.
      reinhardtii VTC2 as an active GDP-L-galactose phosphorylase. C. reinhardtii cells
      exposed to oxidative stress show increased VTC2 mRNA and L-ascorbate levels.
      Genes encoding enzymatic components of the ascorbate-glutathione system (e.g.
      ascorbate peroxidase, manganese superoxide dismutase, and dehydroascorbate
      reductase) are also up-regulated in response to increased oxidative stress. These
      results indicate that C. reinhardtii VTC2, like its plant homologs, is a highly
      regulated enzyme in ascorbate biosynthesis in green algae and that, together with
      the ascorbate recycling system, the L-galactose pathway represents the major
      route for providing protective levels of ascorbate in oxidatively stressed algal
      cells.

PMID- 22393049
TI  - Complement-dependent cytotoxicity in neuromyelitis optica requires aquaporin-4
      protein assembly in orthogonal arrays.
AB  - Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the
      central nervous system in which binding of pathogenic autoantibodies (NMO-IgG) to
      astrocyte aquaporin-4 (AQP4) causes complement-dependent cytotoxicity (CDC) and
      inflammation. We previously reported a wide range of binding affinities of NMO
      IgGs to AQP4 in separate tetramers versus intramembrane aggregates (orthogonal
      arrays of particles, OAPs). We report here a second, independent mechanism by
      which CDC is affected by AQP4 assembly. Utilizing lactate dehydrogenase release
      and live/dead cell cytotoxicity assays, we found in different cell lines, and
      with different monoclonal and patient-derived NMO-IgGs, that CDC was greatly
      (>100-fold) reduced in cells expressing M1- versus M23-AQP4. Studies using a M23
      AQP4 mutant containing an OAP-disrupting mutation, and in cells expressing AQP4
      in different M1/M23 ratios, indicated that NMO-IgG-dependent CDC requires AQP4
      OAP assembly. In contrast, antibody-dependent cell-mediated cytotoxicity produced
      by natural killer cells did not depend on AQP4 OAP assembly. Measurements of C1q
      binding and complement attack complex (C9neo) supported the conclusion that the
      greatly enhanced CDC by OAPs is due to efficient, multivalent binding of C1q to
      clustered NMO-IgG on OAPs. We conclude that AQP4 assembly in OAPs is required for
      CDC in NMO, establishing a new mechanism of OAP-dependent NMO pathogenesis.
      Disruption of AQP4 OAPs may greatly reduce NMO-IgG dependent CDC and NMO
      pathology.

PMID- 22393050
TI  - Functional interactions between erythroid Kruppel-like factor (EKLF/KLF1) and
      protein phosphatase PPM1B/PP2Cbeta.
AB  - Erythroid Kruppel-like factor (EKLF; KLF1) is an erythroid-specific transcription
      factor required for the transcription of genes that regulate erythropoiesis. In
      this paper, we describe the identification of a novel EKLF interactor, Ppm1b, a
      serine-threonine protein phosphatase that has been implicated in the attenuation
      of NFkappaB signaling and the regulation of Cdk9 phosphorylation status. We show
      that Ppm1b interacts with EKLF via its PEST1 sequence. However, its genetic
      regulatory role is complex. Using a promoter-reporter assay in an erythroid cell
      line, we show that Ppm1b superactivates EKLF at the beta-globin and BKLF
      promoters, dependent on intact Ppm1b phosphatase activity. Conversely, depletion
      of Ppm1b in CD34(+) cells leads to a higher level of endogenous beta-globin gene
      activation after differentiation. We also observe that Ppm1b likely has an
      indirect role in regulating EKLF turnover via its zinc finger domain. Together,
      these studies show that Ppm1b plays a multilayered role in regulating the
      availability and optimal activity of the EKLF protein in erythroid cells.

PMID- 22393051
TI  - CYP52X1, representing new cytochrome P450 subfamily, displays fatty acid
      hydroxylase activity and contributes to virulence and growth on insect cuticular
      substrates in entomopathogenic fungus Beauveria bassiana.
AB  - Infection of insects by the entomopathogenic fungus Beauveria bassiana proceeds
      via attachment and penetration of the host cuticle. The outermost epicuticular
      layer or waxy layer of the insect represents a structure rich in lipids including
      abundant amounts of hydrocarbons and fatty acids. A member of a novel cytochrome
      P450 subfamily, CYP52X1, implicated in fatty acid assimilation by B. bassiana was
      characterized. B. bassiana targeted gene knockouts lacking Bbcyp52x1 displayed
      reduced virulence when topically applied to Galleria mellonella, but no reduction
      in virulence was noted when the insect cuticle was bypassed using an
      intrahemoceol injection assay. No significant growth defects were noted in the
      mutant as compared with the wild-type parent on any lipids substrates tested
      including alkanes and fatty acids. Insect epicuticle germination assays, however,
      showed reduced germination of DeltaBbcyp52x1 conidia on grasshopper wings as
      compared with the wild-type parent. Complementation of the gene-knock with the
      full-length gene restored virulence and insect epicuticle germination to wild
      type levels. Heterologous expression of CYP52X1 in yeast was used to characterize
      the substrate specificity of the enzyme. CYP52X1 displayed the highest activity
      against midrange fatty acids (C12:0 and C14:0) and epoxy stearic acid, 4-8-fold
      lower activity against C16:0, C18:1, and C18:2, and little to no activity against
      C9:0 and C18:0. Analyses of the products of the C12:0 and C18:1 reactions
      confirmed NADPH-dependent regioselective addition of a terminal hydroxyl to the
      substrates (omega-hydroxylase). These data implicate CYP52X1 as contributing to
      the penetration of the host cuticle via facilitating the assimilation of insect
      epicuticle lipids.

PMID- 22393053
TI  - Analysis of keystone enzyme in Agar hydrolysis provides insight into the
      degradation (of a polysaccharide from) red seaweeds.
AB  - Agars are abundant polysaccharides from marine red algae, and their chemical
      structure consists of alternating D-galactose and 3,6-anhydro-L-galactose
      residues, the latter of which are presumed to make the polymer recalcitrant to
      degradation by most terrestrial bacteria. Here we study a family 117 glycoside
      hydrolase (BpGH117) encoded within a recently discovered locus from the human gut
      bacterium Bacteroides plebeius. Consistent with this locus being involved in
      agarocolloid degradation, we show that BpGH117 is an exo-acting 3,6-anhydro-alpha
      (1,3)-L-galactosidase that removes the 3,6-anhydrogalactose from the non-reducing
      end of neoagaro-oligosaccharides. A Michaelis complex of BpGH117 with
      neoagarobiose reveals the distortion of the constrained 3,6-anhydro-L-galactose
      into a conformation that favors catalysis. Furthermore, this complex, supported
      by analysis of site-directed mutants, provides evidence for an organization of
      the active site and positioning of the catalytic residues that are consistent
      with an inverting mechanism of catalysis and suggests that a histidine residue
      acts as the general acid. This latter feature differs from the vast majority of
      glycoside hydrolases, which use a carboxylic acid, highlighting the alternative
      strategies that enzymes may utilize in catalyzing the cleavage of glycosidic
      bonds.

PMID- 22393052
TI  - Menaquinone-7 is specific cofactor in tetraheme quinol dehydrogenase CymA.
AB  - Little is known about enzymatic quinone-quinol interconversions in the lipid
      membrane when compared with our knowledge of substrate transformations by
      globular enzymes. Here, the smallest example of a quinol dehydrogenase in nature,
      CymA, has been studied. CymA is a monotopic membrane tetraheme c-type cytochrome
      belonging to the NapC/NirT family and central to anaerobic respiration in
      Shewanella sp. Using protein-film electrochemistry, it is shown that vesicle
      bound menaquinone-7 is not only a substrate for this enzyme but is also required
      as a cofactor when converting other quinones. Here, we propose that the high
      concentration of quinones in the membrane negates the evolutionary pressure to
      create a high affinity active site. However, the instability and reactivity of
      reaction intermediate, semiquinone, might require a cofactor that functions to
      minimize damaging side reactions.

PMID- 22393054
TI  - Phosphorylation by protein kinase Calpha regulates RalB small GTPase protein
      activation, subcellular localization, and effector utilization.
AB  - Ras-like (Ral) small GTPases are regulated downstream of Ras and the noncanonical
      Ral guanine nucleotide exchange factor (RalGEF) effector pathway. Despite RalA
      and RalB sharing 82% sequence identity and utilization of shared effector
      proteins, their roles in normal and neoplastic cell growth have been shown to be
      highly distinct. Here, we determined that RalB function is regulated by protein
      kinase Calpha (PKCalpha) phosphorylation. We found that RalB phosphorylation on
      Ser-198 in the C-terminal membrane targeting sequence resulted in enhanced RalB
      endomembrane accumulation and decreased RalB association with its effector, the
      exocyst component Sec5. Additionally, RalB phosphorylation regulated vesicular
      trafficking and membrane fusion by regulating v- and t-SNARE interactions. RalB
      phosphorylation regulated vesicular traffic of alpha5-integrin to the cell
      surface and cell attachment to fibronectin. In summary, our data suggest that
      phosphorylation by PKCalpha is critical for RalB-mediated vesicle trafficking and
      exocytosis.

PMID- 22393055
TI  - Imaging P2X4 receptor lateral mobility in microglia: regulation by calcium and
      p38 MAPK.
AB  - ATP-gated ionotropic P2X4 receptors are up-regulated in activated microglia and
      are critical for the development of neuropathic pain, a microglia-associated
      disorder. However, the nature of how plasma membrane P2X4 receptors are regulated
      in microglia is not fully understood. We used single-molecule imaging to track
      quantum dot-labeled P2X4 receptors to explore P2X4 receptor mobility in the
      processes of resting and activated microglia. We find that plasma membrane P2X4
      receptor lateral mobility in resting microglial processes is largely random,
      consisting of mobile and slowly mobile receptors. Moreover, lateral mobility is
      P2X subunit- and cell-specific, increased in an ATP activation and calcium
      dependent manner, and enhanced in activated microglia by the p38 MAPK pathway
      that selectively regulates slowly mobile receptors. Thus, our data indicate that
      P2X4 receptors are dynamically regulated mobile ATP sensors, sampling more of the
      plasma membrane in response to ATP and during the activated state of microglia
      that is associated with nervous system dysfunction.

PMID- 22393057
TI  - p21-Activated kinase 2 (PAK2) inhibits TGF-beta signaling in Madin-Darby canine
      kidney (MDCK) epithelial cells by interfering with the receptor-Smad interaction.
AB  - TGF-beta (transforming growth factor beta) plays a variety of cellular functions
      mainly through the Smad pathway. Phosphorylation of the carboxyl SXS motif in R
      Smads (Smad2 and Smad3) by the type I receptor TbetaRI is a key step for their
      activation. It has been reported that the serine/threonine kinase PAK2 (p21
      activated kinase 2) can mediate TGF-beta signaling in mesenchymal cells. Here, we
      report that PAK2 restricts TGF-beta-induced Smad2/3 activation and
      transcriptional responsiveness in MDCK epithelial cells. Mechanistically, PAK2
      associates with Smad2 and Smad3 in a kinase activity-dependent manner and blocks
      their activation. PAK2 phosphorylates Smad2 at Ser-417, which is adjacent to the
      L3 loop that contributes to the TbetaRI-R-Smad association. Consistently,
      substitution of Ser-417 with glutamic acid attenuates the interaction of Smad2
      with TbetaRI. Together, our results indicate that PAK2 negatively modulate TGF
      beta signaling by attenuating the receptor-Smad interaction and thus Smad
      activation.

PMID- 22393056
TI  - UDP-glucuronosyltransferase-mediated metabolic activation of the tobacco
      carcinogen 2-amino-9H-pyrido[2,3-b]indole.
AB  - 2-Amino-9H-pyrido[2,3-b]indole (AalphaC) is a carcinogenic heterocyclic aromatic
      amine (HAA) that arises in tobacco smoke. UDP-glucuronosyltransferases (UGTs) are
      important enzymes that detoxicate many procarcinogens, including HAAs. UGTs
      compete with P450 enzymes, which bioactivate HAAs by N-hydroxylation of the
      exocyclic amine group; the resultant N-hydroxy-HAA metabolites form covalent
      adducts with DNA. We have characterized the UGT-catalyzed metabolic products of
      AalphaC and the genotoxic metabolite 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH
      AalphaC) formed with human liver microsomes, recombinant human UGT isoforms, and
      human hepatocytes. The structures of the metabolites were elucidated by (1)H NMR
      and mass spectrometry. AalphaC and HONH-AalphaC underwent glucuronidation by UGTs
      to form, respectively, N(2)-(beta-D-glucosidurony1)-2-amino-9H-pyrido[2,3
      b]indole (AalphaC-N(2)-Gl) and N(2)-(beta-D-glucosidurony1)-2-hydroxyamino-9H
      pyrido[2,3-b]indole (AalphaC-HON(2)-Gl). HONH-AalphaC also underwent
      glucuronidation to form a novel O-linked glucuronide conjugate, O-(beta-D
      glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (AalphaC-HN(2)-O-Gl).
      AalphaC-HN(2)-O-Gl is a biologically reactive metabolite and binds to calf thymus
      DNA (pH 5.0 or 7.0) to form the N-(deoxyguanosin-8-yl)-AalphaC adduct at 20-50
      fold higher levels than the adduct levels formed with HONH-AalphaC. Major UGT
      isoforms were examined for their capacity to metabolize AalphaC and HONH-AalphaC.
      UGT1A4 was the most catalytically efficient enzyme (V(max)/K(m)) at forming
      AalphaC-N(2)-Gl (0.67 MUl.min(-1).mg of protein(-1)), and UGT1A9 was most
      catalytically efficient at forming AalphaC-HN-O-Gl (77.1 MUl.min(-1).mg of
      protein(-1)), whereas UGT1A1 was most efficient at forming AalphaC-HON(2)-Gl (5.0
      MUl.min(-1).mg of protein(-1)). Human hepatocytes produced AalphaC-N(2)-Gl and
      AalphaC-HN(2)-O-Gl in abundant quantities, but AalphaC-HON(2)-Gl was a minor
      product. Thus, UGTs, usually important enzymes in the detoxication of many
      procarcinogens, serve as a mechanism of bioactivation of HONH-AalphaC.

PMID- 22393058
TI  - Sialidase NEU4 hydrolyzes polysialic acids of neural cell adhesion molecules and
      negatively regulates neurite formation by hippocampal neurons.
AB  - Modulation of levels of polysialic acid (polySia), a sialic acid polymer,
      predominantly associated with the neural cell adhesion molecule (NCAM),
      influences neural functions, including synaptic plasticity, neurite growth, and
      cell migration. Biosynthesis of polySia depends on two polysialyltransferases
      ST8SiaII and ST8SiaIV in vertebrate. However, the enzyme involved in degradation
      of polySia in its physiological turnover remains uncertain. In the present study,
      we identified and characterized a murine sialidase NEU4 that catalytically
      degrades polySia. Murine NEU4, dominantly expressed in the brain, was found to
      efficiently hydrolyze oligoSia and polySia chains as substrates in sialidase in
      vitro assays, and also NCAM-Fc chimera as well as endogenous NCAM in tissue
      homogenates of postnatal mouse brain as assessed by immunoblotting with anti
      polySia antibodies. Degradation of polySia by NEU4 was also evident in
      neuroblastoma Neuro2a cells that were co-transfected with Neu4 and ST8SiaIV
      genes. Furthermore, in mouse embryonic hippocampal primary neurons, the
      endogenously expressed NEU4 was found to decrease during the neuronal
      differentiation. Interestingly, GFP- or FLAG-tagged NEU4 was partially co
      localized with polySia in neurites and significantly suppressed their outgrowth,
      whereas silencing of NEU4 showed the acceleration together with an increase in
      polySia expression. These results suggest that NEU4 is involved in regulation of
      neuronal function by polySia degradation in mammals.

PMID- 22393059
TI  - Analysis of binding sites on complement factor I using artificial N-linked
      glycosylation.
AB  - Factor I (FI) is a serine protease that inhibits all complement pathways by
      degrading activated complement components C3b and C4b. FI functions only in the
      presence of several cofactors, such as factor H, C4b-binding protein, complement
      receptor 1, and membrane cofactor protein. FI is composed of two chains linked by
      a disulfide bridge; the light chain comprises only the serine protease (SP)
      domain, whereas the heavy chain contains the FI membrane attack complex domain
      (FIMAC), CD5 domain, and low density lipoprotein receptor 1 (LDLr1) and LDLr2
      domains. To better understand how FI inhibits complement, we used homology-based
      three-dimensional models of FI domains in an attempt to identify potential
      protein-protein interaction sites. Specific amino acids were then mutated to
      yield 20 recombinant mutants of FI carrying additional surface-exposed N
      glycosylation sites that were expected to sterically hinder interactions. The
      Michaelis constant (K(m)) of all FI mutants toward a small substrate was not
      increased. We found that many mutations in the FIMAC and SP domains nearly
      abolished the ability of FI to degrade C4b and C3b in the fluid phase and on the
      surface, irrespective of the cofactor used. On the other hand, only a few
      alterations in the CD5 and LDLr1/2 domains impaired this activity. In conclusion,
      all analyzed cofactors form similar trimolecular complexes with FI and C3b/C4b,
      and the accessibility of FIMAC and SP domains is crucial for the function of FI.

PMID- 22393060
TI  - The helicase HAGE expressed by malignant melanoma-initiating cells is required
      for tumor cell proliferation in vivo.
AB  - Malignant melanoma-initiating cells (MMIC) are a subpopulation of cells
      responsible for melanoma tumor growth and progression. They are defined by the
      expression of the ATP-binding cassette (ABC) subfamily B member 5 (ABCB5). Here,
      we identified a critical role for the DEAD-box helicase antigen (HAGE) in ABCB5+
      MMIC-dependent tumorigenesis and show that HAGE-specific inactivation inhibits
      melanoma tumor growth mediated by this tumor-initiating population. Knockdown of
      HAGE led to a significant decrease in RAS protein expression with a concomitant
      decrease in activation of the AKT and ERK signaling pathways implicated to play
      an important role in melanoma progression. To confirm that the reduction in NRAS
      (Neuroblastoma RAS) expression was dependent on the HAGE helicase activity, we
      showed that NRAS, effectively silenced by siRNA, could be rescued by
      reintroduction of HAGE in cells lacking HAGE. Furthermore, we provide a mechanism
      by which HAGE promotes NRAS unwinding in vitro. We also observed using tumor
      transplantation in Non-obese diabetic/severe combined immunodeficiency mice that
      the HAGE knockdown in a ABCB5+ melanoma cell line displayed a significant
      decrease in tumor growth and compared with the control. Our results suggest that
      the helicase HAGE is required for ABCB5+ MMIC-dependent tumor growth through
      promoting RAS protein expression and that cancer therapies targeting HAGE
      helicase may have broad applications for treating malignant melanoma and
      potentially other cancer types.

PMID- 22393061
TI  - Possible role of Efnb1 protein, a ligand of Eph receptor tyrosine kinases, in
      modulating blood pressure.
AB  - Eph kinases constitute the largest receptor tyrosine kinase family, and their
      ligands, ephrins (Efns), are also cell surface molecules. Although they are
      ligands, Efns can transduce signals reversely into cells. We have no prior
      knowledge of the role played by any members of this family of kinases or their
      ligands in blood pressure (BP) regulation. In the present studies, we
      investigated the role of Efnb1 in vascular smooth muscle cell (VSMC)
      contractility and BP regulation. We revealed that reverse signaling through Efnb1
      led to a reduction of RhoA activation and VSMC contractility in vitro. Consistent
      with this finding, ex vivo, there was an increase of RhoA activity accompanied by
      augmented myosin light chain phosphorylation in mesenteric arteries from mice
      with smooth muscle-specific conditional Efnb1 gene knock-out (KO). Small
      interfering RNA knockdown of Grip1, a molecule associated with the Efnb1
      intracellular tail, partially eliminated the effect of Efnb1 on VSMC
      contractility and myosin light chain phosphorylation. In support of these in
      vitro and ex vivo results, Efnb1 KO mice on a high salt diet showed a
      statistically significant heightened increment of BP at multiple time points
      during stress compared with wild type littermates. Our results demonstrate that
      Efnb1 is a previously unknown negative regulator of VSMC contractility and BP and
      that it exerts such effects via reverse signaling through Grip1.

PMID- 22393062
TI  - Involvement of Beclin 1 in engulfment of apoptotic cells.
AB  - Efficient apoptotic cell engulfment is important for both tissue homeostasis and
      immune response in mammals. In the present study, we report that Beclin 1 (a
      regulator of autophagy) is required for apoptotic cell engulfment. The engulfment
      process was largely abolished in Beclin 1 knock-out cells, and Beclin 1 knockdown
      significantly decreased apoptotic cell internalization in macrophage and
      fibroblast cell lines. Beclin 1 was recruited to the early phagocytic cup along
      with the generation of phosphatidylinositol 3-phosphate and Rac1, which regulates
      actin dynamics in lamellipodia. No lamellipodia were formed in Beclin 1 knock-out
      cells, and Beclin 1 knockdown completely inhibited the promotion of engulfment by
      ectopic expression of Rac1. Beclin 1 was co-immunoprecipitated with Rac1. These
      data indicate that Beclin 1 coordinates actin dynamics and membrane phospholipid
      synthesis to promote efficient apoptotic cell engulfment.

PMID- 22393063
TI  - Cross-seeding and conformational selection between three- and four-repeat human
      Tau proteins.
AB  - In Alzheimer's disease and frontotemporal dementias, the microtubule-associated
      protein Tau forms intracellular paired helical filaments. The filaments can form
      not only by the full-length human Tau protein, but also by the three repeated
      (K19) or four repeated (K18) Tau segments. However, of interest, experimentally,
      K19 can seed K18, but not vice versa. To obtain insight into the cross-seeding
      between K18 and K19 aggregates, here, K18 and K19 octamers with repeat 3 (R3) in
      U-shaped, L-shaped, and long straight line-shaped (SL-shape) conformations are
      assembled into different structures. The simulation results show that K18-8/K19-8
      (K18 and K19 assemblies number 8) with R3 in an L shape and K18-9/K19-9 with R3
      in an SL shape are highly populated and present the highest structural similarity
      among all simulated K18 and K19 octamers, suggesting that similar folding of
      K18/K19 may serve as structural core for the K18-K19 co-assembled heterogeneous
      filament. We demonstrate that formation of stable R2 and R3 conformations is the
      critical step for K18 aggregation, and R3 is critical for K19 fibrillization. The
      different core units in K18 and K19 may create a cross-seeding barrier for the
      K18 seed to trigger K19 fibril growth because R2 is not available for K19. Our
      study provides insights into cross-seeding involving heterogeneous structures.
      The polymorphic nature of protein aggregation could be magnified in the cross
      seeding process. If the seeding conformations lead to too much divergence in the
      energy landscape, it could impede fibril formation. Such an effect could also
      contribute to the asymmetric barrier between K18 and K19.

PMID- 22393064
TI  - Phenolic compounds prevent amyloid beta-protein oligomerization and synaptic
      dysfunction by site-specific binding.
AB  - Cerebral deposition of amyloid beta protein (Abeta) is an invariant feature of
      Alzheimer disease (AD), and epidemiological evidence suggests that moderate
      consumption of foods enriched with phenolic compounds reduce the incidence of AD.
      We reported previously that the phenolic compounds myricetin (Myr) and rosmarinic
      acid (RA) inhibited Abeta aggregation in vitro and in vivo. To elucidate a
      mechanistic basis for these results, we analyzed the effects of five phenolic
      compounds in the Abeta aggregation process and in oligomer-induced synaptic
      toxicities. We now report that the phenolic compounds blocked Abeta
      oligomerization, and Myr promoted significant NMR chemical shift changes of
      monomeric Abeta. Both Myr and RA reduced cellular toxicity and synaptic
      dysfunction of the Abeta oligomers. These results suggest that Myr and RA may
      play key roles in blocking the toxicity and early assembly processes associated
      with Abeta through different binding.

PMID- 22393066
TI  - An exploration of patient perceptions of adherence to tuberculosis treatment in
      Tanzania.
AB  - In this study, we aimed to explore patient perceptions of adherence to
      tuberculosis (TB) treatment and construct a theoretical model of treatment
      adherence behavior. We conducted semistructured interviews with 11 adherent
      patients from Tanzania whom we recruited by purposive sampling. The interview
      data were analyzed by content analysis. We found that the patient's intention to
      adhere is the most important determinant of adherence behavior. This intention is
      preceded by the decision to seek biomedical health care, and based on knowledge
      and beliefs about TB treatment and the motivation to be cured. The intention to
      adhere helps patients to cope with perceived barriers to adherence, such as
      socioeconomic difficulties, and to create an adherence-enabling environment in
      which the presence of social support plays an important role. Our preliminary
      adherence behavior model should be validated in larger, nonadherent patient
      populations and evaluated for its applicability to the development of adherence
      promoting strategies.

PMID- 22393065
TI  - American Muslim perceptions of healing: key agents in healing, and their roles.
AB  - American Muslims represent a growing and diverse community. Efforts at promoting
      cultural competence, enhancing cross-cultural communication skills, and improving
      community health must account for the religio-cultural frame through which
      American Muslims view healing. Using a community-based participatory research
      model, we conducted 13 focus groups at area mosques in southeast Michigan to
      explore American Muslim views on healing and to identify the primary agents, and
      their roles, within the healing process. Participants shared a God-centric view
      of healing. Healing was accessed through direct means such as supplication and
      recitation of the Qur'an, or indirectly through human agents including imams,
      health care practitioners, family, friends, and community. Human agents served
      integral roles, influencing spiritual, psychological, and physical health.
      Additional research into how religiosity, health care systems, and community
      factors influence health-care-seeking behaviors is warranted.

PMID- 22393069
TI  - Re-rethinking the article by Thombs and colleagues.

PMID- 22393071
TI  - Hospital parking fees.

PMID- 22393072
TI  - Hospital parking fees.

PMID- 22393073
TI  - Hospital parking fees.

PMID- 22393074
TI  - Hospital parking fees.

PMID- 22393075
TI  - In vitro analysis of balloon cuffing phenomenon: inherent biophysical properties
      of catheter material or mechanics of catheter balloon deflation?
AB  - AIM: To investigates the different methods of balloon deflation, types of urinary
      catheters and exposure to urine media in catheter balloon cuffing. MATERIALS AND
      METHODS: Bardex(r), Bard-Lubri-Sil(r), Argyle(r), Releen(r) and Biocath(r) were
      tested in sterile and E.Coli inoculated urine at 0, 14 and 28 days. Catheter
      deflation was performed with active deflation; passive deflation; passive auto
      deflation; and excision of the balloon inflow channel. Balloon cuffing was
      assessed objectively by running the deflated balloon over a plate of agar and
      subjectively by 3 independent observers. RESULTS: Bardex(r), Argyle(r) and
      Biocath(r) showed greater degree of catheter balloon cuffing (p < 0.01). Active
      balloon deflation was the worst method (p < 0.01). The presence of infected urine
      media also contributed to greater balloon cuffing (p > 0.05). Linear regression
      model analysis confirmed time as the most significant factor. CONCLUSION: The
      duration of catheters exposure, different deflation methods and types of
      catheters tested contributed significantly to catheter balloon cuffing (p <
      0.01).

PMID- 22393076
TI  - Single-incision laparoscopic resection of Bismuth I hilar cholangiocarcinoma.
AB  - INTRODUCTION: Laparoscopic hilar cholangiocarcinoma is rarely performed because
      of its aggressive growth and complicated anatomy. The authors successfully
      performed single-incision laparoscopic resection of Bismuth I hilar
      cholangiocarcinoma in 2 cases. METHOD: Two cases with Bismuth I
      cholangiocarcinoma were chosen for the laparoscopic surgery. Segmental bile duct
      resection and hepatoduodenal ligament lymphadenectomy were performed using single
      incision laparoscopic technique with conventional instruments. RESULTS: Two
      operations were successfully performed without conversion. The operation time was
      300 and 350 minutes, respectively. The margins of proximal and distal bile ducts
      were negative. The hospital stay was 6 and 9 days, respectively. One dosage of
      analgesic was administered after surgery. The abdominal wound recovered very well
      with good cosmesis. CONCLUSION: Single-incision laparoscopic surgery
      cholangiocarcinoma resection can be optional in strictly selected patients with
      Bismuth I cholangiocarcinoma. Long-term follow-up and more data are needed to
      evaluate its benefits.

PMID- 22393077
TI  - Optimizing surgical approach for natural orifice translumenal endoscopic
      procedures.
AB  - BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) often
      requires some degree of retroflexion of the endoscopic operating system. This
      study investigates the impact of retroflexion on task performance in NOTES.
      METHODS: In a bench-top simulation, surgeons were required to manipulate a single
      channel endoscope to touch 4 dots in a predetermined order. The task was
      performed under the forward-view and retroflexed-view conditions. RESULTS: Tasks
      performed under the forward-view condition were significantly faster than those
      performed under the retroflexed-view condition (P = .005). Also, 5 experienced
      surgeons completed tasks in less time than the novices (P = .043). Experienced
      surgeons were mildly affected by the inverted image, whereas the novices were
      vulnerable to image malalignment. CONCLUSION: Careful selection of the surgical
      approach to avoid image malalignment is suggested for safe performance of NOTES.
      Extensive training is required for novices to overcome the vision-motion
      difficulty before they can perform NOTES safely and effectively.

PMID- 22393078
TI  - [18F]fluorodeoxyglucose positron emission tomography-computed tomography in
      breast cancer: when... and when not?

PMID- 22393079
TI  - Classification of patients with chronic myeloid leukemia on basis of BCR-ABL
      transcript level at 3 months fails to identify patients with low organic cation
      transporter-1 activity destined to have poor imatinib response.

PMID- 22393081
TI  - Doubling down on human epidermal growth factor receptor 2.

PMID- 22393082
TI  - Prognostic patterns in the histopathology of pulmonary adenocarcinoma.

PMID- 22393080
TI  - Cardiovascular status of childhood cancer survivors exposed and unexposed to
      cardiotoxic therapy.
AB  - PURPOSE: To determine whether cardiovascular abnormalities in childhood cancer
      survivors are restricted to patients exposed to cardiotoxic anthracyclines and
      cardiac irradiation and how risk factors for atherosclerotic disease and systemic
      inflammation contribute to global cardiovascular status. METHODS: We assessed
      echocardiographic characteristics and atherosclerotic disease risk in 201
      survivors of childhood cancer with and without exposure to cardiotoxic treatments
      at a median of 11 years after diagnosis (range, 3 to 32 years) and in 76 sibling
      controls. RESULTS: The 156 exposed survivors had below normal left ventricular
      (LV) mass, wall thickness, contractility, and fractional shortening and above
      normal LV afterload. The 45 unexposed survivors also had below normal LV mass
      overall, and females had below normal LV wall thickness. Exposed and unexposed
      survivors, compared with siblings, had higher levels of N-terminal pro-brain
      natriuretic peptide (81.7 and 69.0 pg/mL, respectively, v 39.4 pg/mL), higher
      mean fasting serum levels of non-high-density lipoprotein cholesterol (126.5 and
      121.1 mg/dL, respectively, v 109.8 mg/dL), higher insulin levels (10.4 and 10.5
      MUU/mL, respectively, v 8.2 MUU/mL), and higher levels of high-sensitivity C
      reactive protein (2.7 and 3.1 mg/L, respectively, v 0.9 mg/L; P < .001 for all
      comparisons). Age-adjusted, predicted-to-ideal 30-year risk of myocardial
      infarction, stroke, or coronary death was also higher for exposed and unexposed
      survivors compared with siblings (2.16 and 2.12, respectively, v 1.70; P < .01
      for both comparisons). CONCLUSION: Childhood cancer survivors not receiving
      cardiotoxic treatments nevertheless have cardiovascular abnormalities, systemic
      inflammation, and an increased risk of atherosclerotic disease. Survivorship
      guidelines should address cardiovascular concerns, including the risk of
      atherosclerotic disease and systemic inflammation, in exposed and unexposed
      survivors.

PMID- 22393083
TI  - Estrogen receptor in breast ductal carcinoma in situ: good cop, bad cop?

PMID- 22393084
TI  - Pertuzumab monotherapy after trastuzumab-based treatment and subsequent
      reintroduction of trastuzumab: activity and tolerability in patients with
      advanced human epidermal growth factor receptor 2-positive breast cancer.
AB  - PURPOSE: The combination of pertuzumab and trastuzumab resulted in a clinical
      benefit rate (CBR) of 50% in patients with human epidermal growth factor receptor
      2 (HER2) -positive breast cancer whose disease progressed during prior
      trastuzumab-based therapy. To define whether this previously observed encouraging
      activity was a result of the combination of pertuzumab and trastuzumab or of
      pertuzumab alone, we recruited a third cohort of patients who received pertuzumab
      without trastuzumab. We then investigated the impact of reintroducing trastuzumab
      to patients whose disease progressed on pertuzumab monotherapy. PATIENTS AND
      METHODS: Twenty-nine patients with HER2-positive breast cancer whose disease
      progressed during prior trastuzumab-based therapy received pertuzumab (840 mg
      loading dose, then 420 mg every 3 weeks) until progressive disease or
      unacceptable toxicity. Seventeen patients with disease progression continued to
      receive pertuzumab (at the same dose), with the addition of trastuzumab (4 mg/kg
      loading dose and then 2 mg/kg weekly or 8 mg/kg loading dose and then 6 mg/kg
      every 3 weeks). RESULTS: All 29 patients enrolled for pertuzumab monotherapy
      experienced disease progression. The objective response rate (ORR) and CBR were
      3.4% and 10.3%, respectively, during pertuzumab monotherapy. With the addition of
      trastuzumab, the ORR and CBR were 17.6% and 41.2%, respectively. Progression-free
      survival was longer with combination therapy than pertuzumab monotherapy (17.4 v
      7.1 weeks, respectively). Treatment was well tolerated with minimal cardiac
      dysfunction. CONCLUSION: Although pertuzumab has some activity in patients with
      HER2-positive breast cancer that progressed during therapy with trastuzumab, the
      combination of pertuzumab and trastuzumab seems to be more active than
      monotherapy.

PMID- 22393085
TI  - Maximizing human epidermal growth factor receptor 2 inhibition: a new oncologic
      paradigm in the era of targeted therapy.

PMID- 22393086
TI  - Phase II study of weekly vinblastine in recurrent or refractory pediatric low
      grade glioma.
AB  - PURPOSE: To evaluate the efficacy of single-agent vinblastine in pediatric
      patients with recurrent or refractory low-grade glioma. PATIENTS AND METHODS:
      Patients were eligible if they had experienced previous treatment failure
      (chemotherapy and/or radiation) for incompletely resected or unresectable low
      grade glioma (LGG). Vinblastine (6 mg/m(2)) was administered weekly for 1 year
      unless unacceptable toxicity or progression (confirmed on two consecutive imaging
      studies) occurred. RESULTS: Fifty-one patients (age range, 1.4 to 18.2 years;
      median age, 7.2 years) were prospectively enrolled onto this phase II study.
      Fifty patients had previously received at least one prior regimen of
      chemotherapy, and 10 patients had previously received radiation treatment. Fifty
      patients were evaluable for response; 18 patients (36%) had a complete, partial,
      or minor response, and 31 patients completed 1 year of treatment. At a median
      follow-up of 67 months, 23 patients had not experienced progression; three
      patients have died. Five-year overall survival was 93.2% +/- 3.8%, and 5-year
      progression-free survival was 42.3% +/- 7.2%. Toxicity was manageable and mostly
      hematologic, although a few patients needed transfusions. CONCLUSION: Weekly
      vinblastine seems to be a reasonable alternative to radiation for pediatric
      patients with LGG who have experienced treatment failure with first-line
      chemotherapy. The 5-year progression-free survival observed in this phase II
      trial is comparable to results observed with first-line chemotherapy in
      chemotherapy-naive patients. The role of single-agent vinblastine and other vinca
      alkaloid in the management of pediatric LGGs deserves further investigation.

PMID- 22393087
TI  - Radiotherapy in older women with low-risk breast cancer: why did practice not
      change?

PMID- 22393088
TI  - Assessing the impact of a cooperative group trial on breast cancer care in the
      medicare population.
AB  - PURPOSE: The Cancer and Leukemia Group B (CALGB) C9343 trial found that adjuvant
      radiation therapy (RT) provided minimal benefits for older women with breast
      cancer. Although treatment guidelines were changed to indicate that some women
      could forego RT, the impact of the C9343 results on clinical practice is unclear.
      PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results
      (SEER) -Medicare data set to assess the use of adjuvant RT in a sample of women
      >= 70 years old diagnosed with stage I breast cancer from 2001 to 2007 who
      fulfilled the C9343 inclusion criteria. We used log-binomial regression to
      estimate the relation between publication of C9343 and use of RT in the full
      sample and across strata of patient and health system characteristics. RESULTS:
      Of the 12,925 Medicare beneficiaries in our sample (mean age, 77.7 years), 76.5%
      received RT. Approximately 79% of women received RT before study publication
      compared with 75% after (adjusted relative risk of receiving RT postpublication v
      prepublication: 0.97; 95% CI, 0.95 to 0.98). Although use of RT was lower after
      the trial within all strata of age and life expectancy, the magnitude of this
      decrease did not differ significantly by strata. For instance, among patients
      with life expectancy less than 5 years, RT use decreased by 3.7%, from 44.4%
      prepublication to 40.7% postpublication. Among patients with life expectancy >=
      10 years, RT use decreased by 3.0%, from 92.0% to 89.0%. CONCLUSION: The C9343
      trial had minimal impact on the use of RT among older women in the Medicare
      population, even among the oldest women and those with shorter life expectancies.

PMID- 22393090
TI  - The Cinderella of medical disciplines.

PMID- 22393089
TI  - Prospective study of 2-[18F]fluorodeoxyglucose positron emission tomography in
      the assessment of regional nodal spread of disease in patients with breast
      cancer: an Ontario clinical oncology group study.
AB  - PURPOSE: 2-[(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is
      potentially useful in assessing lymph nodes and detecting distant metastases in
      women with primary breast cancer. PATIENTS AND METHODS: Women diagnosed with
      operable breast cancer within 3 months underwent FDG-PET at one of five Ontario
      study centers followed by axillary lymph node assessment (ALNA) consisting of
      sentinel lymph node biopsy (SLNB) alone if sentinel lymph nodes (SLNs) were
      negative, SLNB with axillary lymph node dissection (ALND) if SLNB or PET was
      positive, or ALND alone if SLNs were not identified. RESULTS: Between January
      2005 and March 2007, 325 analyzable women entered this study. Sentinel nodes were
      found for 312 (96%) of 325 women and were positive for tumor in 90 (29%) of 312.
      ALND was positive in seven additional women. Using ALNA as the gold standard,
      sensitivity for PET was 23.7% (95% CI, 15.9% to 33.6%), specificity was 99.6%
      (95% CI, 97.2% to 99.9%), positive predictive value was 95.8% (95% CI, 76.9% to
      99.8%), negative predictive value was 75.4% (95% CI, 70.1% to 80.1%), and
      prevalence was 29.8% (95% CI, 25.0% to 35.2%). Using logistic regression, tumor
      size was predictive for prevalence of tumor in the axilla and for PET
      sensitivity. PET scan was suspicious for distant metastases in 13 patients; three
      (0.9%) were confirmed as metastatic disease and 10 (3.0%) were false positive.
      CONCLUSION: FDG-PET is not sufficiently sensitive to detect positive axillary
      lymph nodes, nor is it sufficiently specific to appropriately identify distant
      metastases. However, the very high positive predictive value (96%) suggests that
      PET when positive is indicative of disease in axillary nodes, which may influence
      surgical care.

PMID- 22393091
TI  - Trees, forests, and other implications of a BRAF mutant gene signature in
      patients with BRAF wild-type disease.

PMID- 22393092
TI  - Overall survival: patient outcome, therapeutic objective, clinical trial end
      point, or public health measure?

PMID- 22393094
TI  - Alternative approach to insulin-like growth factor-1 inhibition for treatment of
      breast cancer.

PMID- 22393093
TI  - Survival of older patients with cancer in the Veterans Health Administration
      versus fee-for-service Medicare.
AB  - PURPOSE: The Veterans Health Administration (VHA) provides high-quality
      preventive chronic care and cancer care, but few studies have documented improved
      patient outcomes that result from this high-quality care. We compared the
      survival rates of older patients with cancer in the VHA and fee-for-service (FFS)
      Medicare and examined whether differences in the stage at diagnosis, receipt of
      guideline-recommended therapies, and unmeasured characteristics explain survival
      differences. PATIENTS AND METHODS: We used propensity-score methods to compare
      all-cause and cancer-specific survival rates for men older than age 65 years who
      were diagnosed or received their first course of treatment for colorectal, lung,
      lymphoma, or multiple myeloma in VHA hospitals from 2001 to 2004 to similar FFS
      Medicare enrollees diagnosed in Surveillance, Epidemiology, and End Results
      (SEER) areas in the same time frame. We examined the role of unmeasured factors
      by using sensitivity analyses. RESULTS: VHA patients versus similar FFS SEER
      Medicare patients had higher survival rates of colon cancer (adjusted hazard
      ratio [HR], 0.87; 95% CI, 0.82 to 0.93) and non-small-cell lung cancer (NSCLC;
      HR, 0.91; 95% CI, 0.88 to 0.95) and similar survival rates of rectal cancer (HR,
      1.05; 95% CI, 0.95 to 1.16), small-cell lung cancer (HR, 0.99; 95% CI, 0.93 to
      1.05), diffuse large-B-cell lymphoma (HR, 1.02; 95% CI, 0.89 to 1.18), and
      multiple myeloma (HR, 0.92; 95% CI, 0.83 to 1.03). The diagnosis of VHA patients
      at earlier stages explained much of the survival advantages for colon cancer and
      NSCLC. Sensitivity analyses suggested that additional adjustment for the severity
      of comorbid disease or performance status could have substantial effects on
      estimated differences. CONCLUSION: The survival rate for older men with cancer in
      the VHA was better than or equivalent to the survival rate for similar FFS
      Medicare beneficiaries. The VHA provision of high-quality care, particularly
      preventive care, can result in improved patient outcomes.

PMID- 22393095
TI  - Identification of a poor-prognosis BRAF-mutant-like population of patients with
      colon cancer.
AB  - PURPOSE: Our purpose was development and assessment of a BRAF-mutant gene
      expression signature for colon cancer (CC) and the study of its prognostic
      implications. MATERIALS AND METHODS: A set of 668 stage II and III CC samples
      from the PETACC-3 (Pan-European Trails in Alimentary Tract Cancers) clinical
      trial were used to assess differential gene expression between c.1799T>A
      (p.V600E) BRAF mutant and non-BRAF, non-KRAS mutant cancers (double wild type)
      and to construct a gene expression-based classifier for detecting BRAF mutant
      samples with high sensitivity. The classifier was validated in independent data
      sets, and survival rates were compared between classifier positive and negative
      tumors. RESULTS: A 64 gene-based classifier was developed with 96% sensitivity
      and 86% specificity for detecting BRAF mutant tumors in PETACC-3 and independent
      samples. A subpopulation of BRAF wild-type patients (30% of KRAS mutants, 13% of
      double wild type) showed a gene expression pattern and had poor overall survival
      and survival after relapse, similar to those observed in BRAF-mutant patients.
      Thus they form a distinct prognostic subgroup within their mutation class.
      CONCLUSION: A characteristic pattern of gene expression is associated with and
      accurately predicts BRAF mutation status and, in addition, identifies a
      population of BRAF mutated-like KRAS mutants and double wild-type patients with
      similarly poor prognosis. This suggests a common biology between these tumors and
      provides a novel classification tool for cancers, adding prognostic and biologic
      information that is not captured by the mutation status alone. These results may
      guide therapeutic strategies for this patient segment and may help in population
      stratification for clinical trials.

PMID- 22393096
TI  - True patriotism: a generation of commitment to quality in the Veterans Health
      Administration.

PMID- 22393097
TI  - Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC
      versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers.
AB  - PURPOSE: Radiopeptide therapy is commonly performed with a single radioisotope.
      We aimed to compare the effectiveness of somatostatin-based radiopeptide therapy
      with a single versus a combination of radioisotopes. PATIENTS AND METHODS: In a
      cohort study, patients with metastasized neuroendocrine cancer were treated with
      repeated cycles of (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid
      modified Tyr-octreotide ([(90)Y-DOTA]-TOC) or with cycles alternating between
      [(90)Y-DOTA]-TOC and (177)lutetium-labeled DOTA-TOC ([(177)Lu-DOTA]-TOC) until
      tumor progression or permanent toxicity. Multivariable Cox regression and
      competing risk regression were used to study predictors of survival and renal
      toxicity in patients completing three or more treatment cycles. RESULTS: A total
      of 486 patients completed three or more treatment cycles; 237 patients received
      [(90)Y-DOTA]-TOC and 249 patients received [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC.
      Patients receiving [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC had a significantly
      longer survival than patients receiving [(90)Y-DOTA]-TOC alone (5.51 v 3.96
      years; hazard ratio, 0.64; 95% CI, 0.47 to 0.88; P = .006). The rates of severe
      hematologic toxicities (6.3% v 4.4%; P = .25) and severe renal toxicity (8.9% v
      11.2%; P = .47) were comparable in both groups. CONCLUSION: [(90)Y-DOTA]-TOC +
      [(177)Lu-DOTA]-TOC was associated with improved overall survival compared with
      [(90)Y-DOTA]-TOC alone in patients completing three or more cycles of treatment.
      Contrary to the current practice in radiopeptide therapy, our results suggest an
      advantage of using a combination of radioisotopes.

PMID- 22393098
TI  - Cost-utility analysis of primary prophylaxis versus secondary prophylaxis with
      granulocyte colony-stimulating factor in elderly patients with diffuse aggressive
      lymphoma receiving curative-intent chemotherapy.
AB  - PURPOSE: The 2006 American Society of Clinical Oncology (ASCO) guideline
      recommended primary prophylaxis (PP) with granulocyte colony-stimulating factor
      (G-CSF) instead of secondary prophylaxis (SP) for elderly patients with diffuse
      aggressive lymphoma receiving chemotherapy. We examined the cost-effectiveness of
      PP when compared with SP. METHODS: We conducted a cost-utility analysis to
      compare PP to SP for diffuse aggressive lymphoma. We used a Markov model with an
      eight-cycle chemotherapy time horizon with a government-payer perspective and
      Ontario health, economic, and cost data. Data for efficacies of G-CSF,
      probabilities, and utilities were obtained from published literature.
      Probabilistic sensitivity analysis (PSA) was conducted. RESULTS: The incremental
      cost-effectiveness ratio of PP to SP was $700,500 per quality-adjusted life-year
      (QALY). One-way sensitivity analyses (willingness-to-pay threshold =
      $100,000/QALY) showed that if PP were to be cost-effective, the cost of
      hospitalization for febrile neutropenia (FN) had to be more than $31,138 (2.5 * >
      base case), the cost of G-CSF per cycle less than $960 (base case = $1,960), the
      risk of first-cycle FN more than 47% (base case = 24%), or the relative risk
      reduction of FN with G-CSF more than 91% (base case = 41%). Our result was robust
      to all variables. PSA revealed a 10% probability of PP being cost-effective over
      SP at a willingness-to-pay threshold of $100,000/QALY. CONCLUSION: PP is not cost
      effective when compared with SP in this population. PP becomes attractive only if
      the cost of hospitalization for FN is significantly higher or the cost of G-CSF
      is significantly lower.

PMID- 22393099
TI  - Homonymous hemianopsia in a patient with Hodgkin's lymphoma in remission after
      BEACOPP chemotherapy.

PMID- 22393100
TI  - The novel histologic International Association for the Study of Lung
      Cancer/American Thoracic Society/European Respiratory Society classification
      system of lung adenocarcinoma is a stage-independent predictor of survival.
AB  - PURPOSE: Our aim was to analyze and validate the prognostic impact of the novel
      International Association for the Study of Lung Cancer (IASLC)/American Thoracic
      Society (ATS)/European Respiratory Society (ERS) proposal for an architectural
      classification of invasive pulmonary adenocarcinomas (ADCs) across all tumor
      stages. PATIENTS AND METHODS: The architectural pattern of a large cohort of 500
      patients with resected ADCs (stages I to IV) was retrospectively analyzed in 5%
      increments and classified according to their predominant architecture (lepidic,
      acinar, solid, papillary, or micropapillary), as proposed by the IASLC/ATS/ERS.
      Subsequently, histomorphologic data were correlated with clinical data, adjuvant
      therapy, and patient outcome. RESULTS: Overall survival differed significantly
      between lepidic (78.5 months), acinar (67.3 months), solid (58.1 months),
      papillary (48.9 months), and micropapillary (44.9 months) predominant ADCs (P =
      .007). When patterns were lumped into groups, this resulted in even more
      pronounced differences in survival (pattern group 1, 78.5 months; group 2, 67.3
      months; group 3, 57.2 months; P = .001). Comparable differences were observed for
      overall, disease-specific, and disease-free survival. Pattern and pattern groups
      were stage- and therapy-independent prognosticators for all three survival
      parameters. Survival differences according to patterns were influenced by
      adjuvant chemoradiotherapy; in particular, solid-predominant tumors had an
      improved prognosis with adjuvant radiotherapy. The predominant pattern was
      tightly linked to the risk of developing nodal metastases (P < .001). CONCLUSION:
      Besides all recent molecular progress, architectural grading of pulmonary ADCs
      according to the novel IASLC/ATS/ERS scheme is a rapid, straightforward, and
      efficient discriminator for patient prognosis and may support patient
      stratification for adjuvant chemoradiotherapy. It should be part of an integrated
      clinical, morphologic, and molecular subtyping to further improve ADC treatment.

PMID- 22393101
TI  - Adjuvant tamoxifen reduces subsequent breast cancer in women with estrogen
      receptor-positive ductal carcinoma in situ: a study based on NSABP protocol B-24.
AB  - PURPOSE: The NSABP (National Surgical Adjuvant Breast and Bowel Project) B-24
      study demonstrated significant benefit with adjuvant tamoxifen in patients with
      ductal carcinoma in situ (DCIS) after lumpectomy and radiation. Patients were
      enrolled without knowledge of hormone receptor status. The current study
      retrospectively evaluated the relationship between receptors and response to
      tamoxifen. PATIENTS AND METHODS: Estrogen (ER) and progesterone receptors (PgR)
      were evaluated in 732 patients with DCIS (41% of original study population). An
      experienced central laboratory determined receptor status in all patient cases
      with available paraffin blocks (n = 449) by immunohistochemistry (IHC) using
      comprehensively validated assays. Results for additional patients (n = 283)
      determined by various methods (primarily IHC) were available from enrolling
      institutions. Combined results were evaluated for benefit of tamoxifen by
      receptor status at 10 years and overall follow-up (median, 14.5 years). RESULTS:
      ER was positive in 76% of patients. Patients with ER-positive DCIS treated with
      tamoxifen (v placebo) showed significant decreases in subsequent breast cancer at
      10 years (hazard ratio [HR], 0.49; P < .001) and overall follow-up (HR, 0.60; P =
      .003), which remained significant in multivariable analysis (overall HR, 0.64; P
      = .003). Results were similar, but less significant, when subsequent ipsilateral
      and contralateral, invasive and noninvasive, breast cancers were considered
      separately. No significant benefit was observed in ER-negative DCIS. PgR and
      either receptor were positive in 66% and 79% of patients, respectively, and in
      general, neither was more predictive than ER alone. CONCLUSION: Patients in NSABP
      B-24 with ER-positive DCIS receiving adjuvant tamoxifen after standard therapy
      showed significant reductions in subsequent breast cancer. The use of adjuvant
      tamoxifen should be considered for patients with DCIS.

PMID- 22393102
TI  - Metastatic mixed germ-cell neoplasm presenting as retinal detachment.

PMID- 22393103
TI  - Von hippel-lindau disease and erythrocytosis.

PMID- 22393104
TI  - Refining the use of endocrine therapy for ductal carcinoma in situ.

PMID- 22393105
TI  - Effect of angiostatin on 1,2-dimethylhydrazine-induced colon cancer in mice.
AB  - Antiangiogenic therapy is supposed to be an attractive approach for antitumor
      treatment. Human plasminogen-derived angiostatin K1-3 is one of the most potent
      antiangiogenic agents known currently. However, it is unclear whether angiostatin
      has got protective effects on colon cancer. So we investigated the protective
      effects of angiostatin on 1,2-dimethylhydrazine (DMH)-induced colon cancer in
      mice. Thirty Balb/C male mice, weighing 25-30 g and 8 weeks of age, were used.
      Twenty of the mice were treated with DMH subcutaneously (20 mg/kg) once a week
      for 12 weeks. Six mice died during the DMH injection and surviving mice were
      divided into two groups (7 mice in DMH and 7 mice in DMH + angiostatin groups).
      In the angiostatin group, 6 weeks after the last DMH injection the animals were
      first treated with angiostatin (20 MUg/mouse) intraperitoneally and then
      subcutaneously every 48 h (5 MUg/mouse) throughout a period of 12 weeks. The
      animals were killed after 30 weeks for histopathological examination. When we
      look at the distribution of lesions in the colon, they mainly occurred in the
      distal colon. The incidence of mean colonic lesions in a tumor-bearing mouse was
      9.85 +/- 4.91 in those treated with DMH and 8.71 +/- 3.49 in those treated with
      angiostatin. The incidence of colon tumors was not significantly affected by low
      dose of angiostatin, and we noticed that the number of lesions decreased by 12%
      in DMH + angiostatin group compared to the number of the lesions in DMH group,
      but this decrease was not statistically significant (p > 0.05). The
      administration period of angiostatin corresponds to the precancerous period and
      the reduction in the number of lesions could be important for the protective
      function of angiostatin in DMH + angiostain group. We assume that therapeutic
      effects of angiostatin are related to its doses, route of administration,
      frequency and administration period. In addition, we believe that combination of
      high doses of angiostatin with radiation, gene therapy or chemotherapy might be
      successful in proper tumor model. 

PMID- 22393106
TI  - Nonlinear water waves.
AB  - This introduction to the issue provides a review of some recent developments in
      the study of water waves. The content and contributions of the papers that make
      up this Theme Issue are also discussed.

PMID- 22393107
TI  - Seismically generated tsunamis.
AB  - People around the world know more about tsunamis than they did 10 years ago,
      primarily because of two events: a tsunami on 26 December 2004 that killed more
      than 200,000 people around the shores of the Indian Ocean; and an earthquake and
      tsunami off the coast of Japan on 11 March 2011 that killed nearly 15,000 more
      and triggered a nuclear accident, with consequences that are still unfolding.
      This paper has three objectives: (i) to summarize our current knowledge of the
      dynamics of tsunamis; (ii) to describe how that knowledge is now being used to
      forecast tsunamis; and (iii) to suggest some policy changes that might protect
      people better from the dangers of future tsunamis.

PMID- 22393108
TI  - Theoretical and experimental study of particle trajectories for nonlinear water
      waves propagating on a sloping bottom.
AB  - A third-order asymptotic solution in Lagrangian description for nonlinear water
      waves propagating over a sloping beach is derived. The particle trajectories are
      obtained as a function of the nonlinear ordering parameter epsilon and the bottom
      slope alpha to the third order of perturbation. A new relationship between the
      wave velocity and the motions of particles at the free surface profile in the
      waves propagating on the sloping bottom is also determined directly in the
      complete Lagrangian framework. This solution enables the description of wave
      shoaling in the direction of wave propagation from deep to shallow water, as well
      as the successive deformation of wave profiles and water particle trajectories
      prior to breaking. A series of experiments are conducted to investigate the
      particle trajectories of nonlinear water waves propagating over a sloping bottom.
      It is shown that the present third-order asymptotic solution agrees very well
      with the experiments.

PMID- 22393109
TI  - Note on the velocity and related fields of steady irrotational two-dimensional
      surface gravity waves.
AB  - The velocity and other fields of steady two-dimensional surface gravity waves in
      irrotational motion are investigated numerically. Only symmetric waves with one
      crest per wavelength are considered, i.e. Stokes waves of finite amplitude, but
      not the highest waves, nor subharmonic and superharmonic bifurcations of Stokes
      waves. The numerical results are analysed, and several conjectures are made about
      the velocity and acceleration fields.

PMID- 22393110
TI  - On the open sea propagation of water waves generated by a moving bed.
AB  - Within the framework of linear theory, applicable far from the shore, we
      investigate the two-dimensional propagation of waves generated in the ocean by a
      sudden seabed deformation.

PMID- 22393111
TI  - Regularity of rotational travelling water waves.
AB  - Several recent results on the regularity of streamlines beneath a rotational
      travelling wave, along with the wave profile itself, will be discussed. The
      survey includes the classical water wave problem in both finite and infinite
      depth, capillary waves and solitary waves as well. A common assumption in all
      models to be discussed is the absence of stagnation points.

PMID- 22393112
TI  - Regularity for steady periodic capillary water waves with vorticity.
AB  - In the following, we prove new regularity results for two-dimensional steady
      periodic capillary water waves with vorticity, in the absence of stagnation
      points. Firstly, we prove that if the vorticity function has a Holder-continuous
      first derivative, then the free surface is a smooth curve   and the streamlines
      beneath the surface will be real analytic. Furthermore, once we assume that the
      vorticity function is real analytic, it will follow that the wave surface profile
      is itself also analytic. A particular case of this result includes irrotational
      fluid flow where the vorticity is zero. The property of the streamlines being
      analytic allows us to gain physical insight into small-amplitude waves by
      justifying a power-series approach.

PMID- 22393113
TI  - Experimental study of the particle paths in solitary water waves.
AB  - We provide experiments that had been conducted to investigate the particle
      trajectory beneath a solitary water wave. Experimental results show that the
      surface drift is larger than the bottom drift. Meanwhile, the ratio of the net
      horizontal displacement to the total height of the trajectory at the free surface
      and subsurface will decrease with the initial vertical position and increase with
      the relative wave height.

PMID- 22393114
TI  - Models for the formation of a critical layer in water wave propagation.
AB  - A theory is presented which provides a model for the appearance of critical
      layers within the flow below a water wave. The wave propagates over constant
      depth, with constant (non-zero) vorticity. The mechanism described here involves
      adjusting the surface-pressure boundary condition; two models are discussed. In
      the first, the pressure at the surface is controlled (mimicking the movement of a
      low-pressure region associated with a storm) so that the speed and development of
      the pressure region ensure the appearance of a critical layer. In the second, the
      pressure boundary condition is allowed to accommodate the reduction of pressure
      with altitude, although the effects have to be greatly enhanced for this
      mechanism to produce a critical layer. These two problems are analysed using
      formal parameter asymptotics. In the second problem, this leads to a Korteweg-de
      Vries equation for the surface wave, and then the evolution of appropriate
      solutions of this equation gives rise to the appearance of a critical layer near
      the bottom; the corresponding problem at the surface can be formulated but not
      completely resolved. The appearance of a stagnation point and then a critical
      layer, either at the surface or the bottom, are discussed; the nature of the
      flow, and the corresponding streamlines are obtained and some typical flow fields
      are depicted.

PMID- 22393115
TI  - Trajectories of fluid particles in a periodic water wave.
AB  - We compute trajectories of fluid particles in a water wave that propagates with a
      constant shape at a constant speed. The Stokes drift, which asserts that fluid
      particles are pushed forward by a wave, is proved using a new method. Numerical
      examples with various gravity and surface tension coefficients are presented.

PMID- 22393116
TI  - Synthetic tsunamis along the Israeli coast.
AB  - The new mathematical model for tsunami evolution by Tobias & Stiassnie (Tobias &
      Stiassnie 2011 J. Geophys. Res. Oceans 116, C06026) is used to derive a synthetic
      tsunami database for the southern part of the Eastern Mediterranean coast.
      Information about coastal tsunami amplitudes, half-periods, currents and
      inundation levels is presented.

PMID- 22393117
TI  - Eulerian-Lagrangian analysis for particle velocities and trajectories in a pure
      wave motion using particle image velocimetry.
AB  - This paper investigates the velocity and the trajectory of water particles under
      surface waves, which propagate at a constant water depth, using particle image
      velocimetry (PIV). The vector fields and vertical distributions of velocities are
      presented at several phases in one wave cycle. The third-order Stokes wave theory
      was employed to express the physical quantities. The PIV technique's ability to
      measure both temporal and spatial variations of the velocity was proved after a
      series of attempts. This technique was applied to the prediction of particle
      trajectory in an Eulerian scheme. Furthermore, the measured particle path was
      compared with the positions found theoretically by integrating the Eulerian
      velocity to the higher order of a Taylor series expansion. The profile of average
      travelling distance is also presented with a solution of zero net mass flux in a
      closed wave flume.

PMID- 22393118
TI  - Equivalence of weak formulations of the steady water waves equations.
AB  - We prove the equivalence of three weak formulations of the steady water waves
      equations, namely: the velocity formulation, the stream function formulation and
      the Dubreil-Jacotin formulation, under weak Holder regularity assumptions on
      their solutions.

PMID- 22393119
TI  - Immune-mediated agranulocytosis caused by the cocaine adulterant levamisole: a
      case for reactive metabolite(s) involvement.
AB  - The United States Public Health Service Administration is alerting medical
      professionals that a substantial percentage of cocaine imported into the United
      States is adulterated with levamisole, a veterinary pharmaceutical that can cause
      blood cell disorders such as severe neutropenia and agranulocytosis. Levamisole
      was previously approved in combination with fluorouracil for the treatment of
      colon cancer; however, the drug was withdrawn from the U.S. market in 2000
      because of the frequent occurrence of agranulocytosis. The detection of
      autoantibodies such as antithrombin (lupus anticoagulant) and an increased risk
      of agranulocytosis in patients carrying the human leukocyte antigen B27 genotype
      suggest that toxicity is immune-mediated. In this perspective, we provide an
      historical account of the levamisole/cocaine story as it first surfaced in 2008,
      including a succinct review of levamisole pharmacology, pharmacokinetics, and
      preclinical/clinical evidence for levamisole-induced agranulocytosis. Based on
      the available information on levamisole metabolism in humans, we propose that
      reactive metabolite formation is the rate-limiting step in the etiology of
      agranulocytosis associated with levamisole, in a manner similar to other drugs
      (e.g., propylthiouracil, methimazole, captopril, etc.) associated with blood
      dyscrasias. Finally, considering the toxicity associated with levamisole, we
      propose that the 2,3,5,6-tetrahydroimidazo[2,1-b]thiazole scaffold found in
      levamisole be categorized as a new structural alert, which is to be avoided in
      drug design.

PMID- 22393120
TI  - Metabolic switching of BILR 355 in the presence of ritonavir. I. Identifying an
      unexpected disproportionate human metabolite.
AB  - 11-Ethyl-5,11-dihydro-5-methyl-8-[2-[(1-oxido-4-quinolinyl)oxy] ethyl]-6H
      dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one (BILR 355) is an inhibitor of the
      human immunodeficiency virus-1. BILR 355 exhibited a nonlinear pharmacokinetic
      profile and low exposure after oral administration to humans. This article
      describes the in vitro metabolism of BILR 355, which is correlated with the in
      vivo nonlinearity findings. Our in vitro studies had demonstrated that BILR 355
      was extensively metabolized by cytochrome P450 3A. Thus, BILR 355 was
      concomitantly administered with ritonavir (RTV) in an attempt to boost systemic
      exposure, which did occur in humans. In addition, the expectation was that the
      overall metabolism of BILR 355 would be decreased with concomitant administration
      of RTV. Subsequent metabolite profiling was performed using human plasma samples
      obtained from clinical phase Ib studies with concomitant administration of BILR
      355 and RTV. A total of 18 metabolites was observed. Their structures were
      proposed on the basis of high-performance liquid chromatography-tandem mass
      spectrometry technologies, and 10 metabolites were confirmed by comparison with
      synthetic standards. We were surprised to find that a disproportionate human
      metabolite, BILR 516, was uncovered during this metabolite profiling study and
      pharmacokinetic analysis of BILR 516 showed that it had a longer half-life and
      higher exposure than the parent compound at steady state. Of interest, BILR 516
      was not detected in human plasma when BILR 355 was administered alone. Therefore,
      whereas RTV boosted the exposure of BILR 355, it resulted in a significant
      metabolic switching of BILR 355. Overall, this article demonstrates an unusual
      example of metabolic switching and raises concern about the consequence of
      metabolic switching during drug development.

PMID- 22393121
TI  - Metabolic switching of BILR 355 in the presence of ritonavir. II. Uncovering
      novel contributions by gut bacteria and aldehyde oxidase.
AB  - Ritonavir (RTV) was used as a boosting agent to increase the clinical exposure of
      11-ethyl-5,11-dihydro-5-methyl-8-[2-[(1-oxido-4-quinolinyl)oxy]ethyl]-6H
      dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one (BILR 355), an inhibitor of the human
      immunodeficiency virus, by inhibiting the CYP3A-mediated metabolism of BILR 355.
      However, although the levels of BILR 355 increased upon concomitant
      administration of RTV, a metabolite of BILR 355, BILR 516, which was not detected
      previously in humans dosed with BILR 355 alone, became a disproportionate human
      metabolite with levels exceeding the parent levels at steady state. This was an
      unusual finding based on the in vitro and in vivo metabolic profiles of BILR 355
      available at that time. Our studies reveal that BILR 355 is reduced to an
      intermediate, BILR 402, by gut bacteria and the reduced metabolite (BILR 402) is
      then oxidized by aldehyde oxidase to form BILR 516, the disproportionate human
      metabolite. The role of aldehyde oxidase helped to explain the somewhat unique
      formation of BILR 516 in humans compared with preclinical animal species. This
      article underlines the increasing importance of two individually atypical enzymes
      in drug development, gut bacterial biotransformation and aldehyde oxidase, which
      in combination provided a unique metabolic pathway. In addition, this article
      clearly elucidates an example of novel metabolic switching and, it is hoped,
      raises awareness of the potential for metabolic switching in combination drug
      therapies.

PMID- 22393122
TI  - Combined contributions of impaired hepatic CYP2C11 and intestinal breast cancer
      resistance protein activities and expression to increased oral glibenclamide
      exposure in rats with streptozotocin-induced diabetes mellitus.
AB  - The purpose of this study was to evaluate the contributions of impaired
      cytochrome P450 and breast cancer resistance protein (BCRP) activity and
      expression to drug pharmacokinetics under diabetic conditions. Diabetes was
      induced in rats with the intraperitoneal administration of streptozocin.
      Glibenclamide (GLB), a substrate of BCRP, served as a model drug. The
      pharmacokinetics of orally administered GLB (10 mg/kg) were studied. The results
      showed that diabetes mellitus significantly increased exposure (area under the
      curve and peak concentration) to GLB after oral administration. Data from hepatic
      microsomes suggested impairment of GLB metabolism in diabetic rats. GLB
      metabolism in hepatic microsomes was significantly inhibited by a selective
      inhibitor (sulfaphenazole) of CYP2C11 and an anti-CYP2C11 antibody. Western
      blotting further indicated the contribution of impaired CYP2C11 expression to the
      impairment of GLB metabolism. Excretion data showed that ~72% of the orally
      administered dose was excreted in the feces of normal rats, which indicates an
      important role for intestinal BCRP. Diabetes significantly decreased the recovery
      from feces, which was only 40% of the orally administered dose. Results from in
      situ, single-pass, intestinal perfusion experiments revealed that diabetes
      significantly increased the apparent effective permeability and decreased the
      efflux of GLB through the intestine; this suggests impairment of intestinal BCRP
      function, which may play a role in the increased exposure to orally administered
      GLB in diabetic rats. Insulin treatment partly or completely reversed the changes
      in diabetic rats. All results yielded the conclusion that impaired hepatic
      CYP2C11 and intestinal BCRP expression and activity induced by diabetes
      contributed to the increased exposure of orally administered GLB.

PMID- 22393123
TI  - Selective agonism of human pregnane X receptor by individual ginkgolides.
AB  - Ginkgolide A, ginkgolide B, ginkgolide C, and ginkgolide J are structurally
      related terpene trilactones present in Ginkgo biloba extract. Pregnane X receptor
      (PXR), glucocorticoid receptor (GR), and constitutive androstane receptor (CAR)
      regulate the expression of genes involved in diverse biological functions. In the
      present study, we investigated the effects of individual ginkgolides as single
      chemical entities on the function of human PXR (hPXR), human GR (hGR), and human
      CAR (hCAR). In cell-based reporter gene assays, none of the ginkgolides activated
      hGR or hCAR (wild-type and its SV23, SV24, and SV25 splice variants).
      Concentration-response experiments showed that ginkgolide A and ginkgolide B
      activated hPXR and rat PXR to a greater extent than ginkgolide C, whereas
      ginkgolide J had no effect. As determined by a time-resolved fluorescence
      resonance energy transfer competitive binding assay, ginkgolide A and ginkgolide
      B, but not ginkgolide C or ginkgolide J, were shown to bind to the ligand-binding
      domain of hPXR, consistent with molecular docking data. Compared with tetraethyl
      2-(3,5-di-tert-butyl-4-hydroxyphenyl)ethenyl-1,1-bisphosphonate (SR12813) (a
      known agonist of hPXR), ginkgolide A and ginkgolide B were considerably less
      potent in binding to hPXR. These two ginkgolides recruited steroid receptor
      coactivator-1 to hPXR and increased hPXR target gene (CYP3A4) expression, as
      assessed by a mammalian two-hybrid assay and real-time polymerase chain reaction,
      respectively. In conclusion, the individual ginkgolides regulate the function of
      nuclear receptors in a receptor-selective and chemical-dependent manner. This
      study identifies ginkgolide A and ginkgolide B as naturally occurring agonists of
      hPXR and provides mechanistic insight into the structure-activity relationship in
      ligand activation of hPXR.

PMID- 22393124
TI  - Neutrophil depletion impairs natural killer cell maturation, function, and
      homeostasis.
AB  - Natural killer (NK) cells are bone marrow (BM)-derived granular lymphocytes
      involved in immune defense against microbial infections and tumors. In an N-ethyl
      N-nitrosourea (ENU) mutagenesis strategy, we identified a mouse mutant with
      impaired NK cell reactivity both in vitro and in vivo. Dissection of this
      phenotype showed that mature neutrophils were required both in the BM and in the
      periphery for proper NK cell development. In mice lacking neutrophils, NK cells
      displayed hyperproliferation and poor survival and were blocked at an immature
      stage associated with hyporesponsiveness. The role of neutrophils as key
      regulators of NK cell functions was confirmed in patients with severe congenital
      neutropenia and autoimmune neutropenia. In addition to their direct antimicrobial
      activity, mature neutrophils are thus endowed with immunoregulatory functions
      that are conserved across species. These findings reveal novel types of
      cooperation between cells of the innate immune system and prompt examination of
      NK cell functional deficiency in patients suffering from neutropenia-associated
      diseases.

PMID- 22393125
TI  - Primary Epstein-Barr virus infection does not erode preexisting CD8+ T cell
      memory in humans.
AB  - Acute Epstein-Barr virus (EBV) infection results in an unusually robust CD8(+) T
      cell response in young adults. Based on mouse studies, such a response would be
      predicted to result in attrition of preexisting memory to heterologous infections
      like influenza A (Flu) and cytomegalovirus (CMV). Furthermore, many studies have
      attempted to define the lymphocytosis that occurs during acute EBV infection in
      humans, but it is unclear whether bystander T cells contribute to it. To address
      these issues, we performed a longitudinal prospective study of primary EBV
      infection in humans. During acute EBV infection, both preexisting CMV- and Flu
      specific memory CD8(+) T cells showed signs of bystander activation, including up
      regulation of granzyme B. However, they generally did not expand, suggesting that
      the profound CD8(+) lymphocytosis associated with acute EBV infection is composed
      largely of EBV-specific T cells. Importantly, the numbers of CMV- and Flu
      specific T cells were comparable before and after acute EBV infection. The data
      support the concept that, in humans, a robust CD8(+) T cell response creates a
      new memory CD8(+) T cell niche without substantially depleting preexisting memory
      for heterologous infections.

PMID- 22393127
TI  - Stimulation of the neurotrophin receptor TrkB on astrocytes drives nitric oxide
      production and neurodegeneration.
AB  - Neurotrophin growth factors support neuronal survival and function. In this
      study, we show that the expression of the neurotrophin receptor TrkB is induced
      on astrocytes in white matter lesions in multiple sclerosis (MS) patients and
      mice with experimental autoimmune encephalomyelitis (EAE). Surprisingly, mice
      lacking TrkB specifically in astrocytes were protected from EAE-induced
      neurodegeneration. In an in vitro assay, astrocytes stimulated with the TrkB
      agonist brain-derived neurotrophic factor (BDNF) released nitric oxide (NO), and
      conditioned medium from activated astrocytes had detrimental effects on the
      morphology and survival of neurons. This neurodegenerative process was amplified
      by NO produced by neurons. NO synthesis in the central nervous system during EAE
      depended on astrocyte TrkB. Together, these findings suggest that TrkB expression
      on astrocytes may represent a new target for neuroprotective therapies in MS.

PMID- 22393126
TI  - Autocrine VEGF-VEGFR2-Neuropilin-1 signaling promotes glioma stem-like cell
      viability and tumor growth.
AB  - Although vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) is
      traditionally regarded as an endothelial cell protein, evidence suggests that
      VEGFRs may be expressed by cancer cells. Glioblastoma multiforme (GBM) is a
      lethal cancer characterized by florid vascularization and aberrantly elevated
      VEGF. Antiangiogenic therapy with the humanized VEGF antibody bevacizumab reduces
      GBM tumor growth; however, the clinical benefits are transient and invariably
      followed by tumor recurrence. In this study, we show that VEGFR2 is
      preferentially expressed on the cell surface of the CD133(+) human glioma stem
      like cells (GSCs), whose viability, self-renewal, and tumorigenicity rely, at
      least in part, on signaling through the VEGF-VEGFR2-Neuropilin-1 (NRP1) axis. We
      find that the limited impact of bevacizumab-mediated VEGF blockage may reflect
      ongoing autocrine signaling through VEGF-VEGFR2-NRP1, which is associated with
      VEGFR2-NRP1 recycling and a pool of active VEGFR2 within a cytosolic compartment
      of a subset of human GBM cells. Whereas bevacizumab failed to inhibit prosurvival
      effects of VEGFR2-mediated signaling, GSC viability under unperturbed or
      radiation-evoked stress conditions was attenuated by direct inhibition of VEGFR2
      tyrosine kinase activity and/or shRNA-mediated knockdown of VEGFR2 or NRP1. We
      propose that direct inhibition of VEGFR2 kinase may block the highly dynamic VEGF
      VEGFR2-NRP1 pathway and inspire a GBM treatment strategy to complement the
      currently prevalent ligand neutralization approach.

PMID- 22393128
TI  - Low-dose prednisone inclusion in a methotrexate-based, tight control strategy for
      early rheumatoid arthritis: a randomized trial.
AB  - BACKGROUND: Treatment strategies for tight control of early rheumatoid arthritis
      (RA) are highly effective but can be improved. OBJECTIVE: To investigate whether
      adding prednisone, 10 mg/d, at the start of a methotrexate (MTX)-based treatment
      strategy for tight control in early RA increases its effectiveness. DESIGN: A 2
      year, prospective, randomized, placebo-controlled, double-blind, multicenter
      trial (CAMERA-II [Computer Assisted Management in Early Rheumatoid Arthritis
      trial-II]). (International Standard Randomised Controlled Trial Number: ISRCTN
      70365169) SETTING: 7 hospitals in the Netherlands. PATIENTS: 236 patients with
      early RA (duration <1 year). INTERVENTION: Patients were randomly assigned to an
      MTX-based, tight control strategy starting with either MTX and prednisone or MTX
      and placebo. Methotrexate treatment was tailored to the individual patient at
      monthly visits on the basis of predefined response criteria aiming for remission.
      MEASUREMENTS: The primary outcome was radiographic erosive joint damage after 2
      years. Secondary outcomes included response criteria, remission, and the need to
      add cyclosporine or a biologic agent to the treatment. RESULTS: Erosive joint
      damage after 2 years was limited and less in the group receiving MTX and
      prednisone (n = 117) than in the group receiving MTX and placebo (n = 119). The
      MTX and prednisone strategy was also more effective in reducing disease activity
      and physical disability, achieving sustained remission, and avoiding the addition
      of cyclosporine or biologic treatment. Adverse events were similar in both
      groups, but some occurred less in the MTX and prednisone group. LIMITATION: A
      tight control strategy for RA implies monthly visits to an outpatient clinic,
      which is not always feasible. CONCLUSION: Inclusion of low-dose prednisone in an
      MTX-based treatment strategy for tight control in early RA improves patient
      outcomes. PRIMARY FUNDING SOURCE: Catharijne Foundation.

PMID- 22393129
TI  - Do physicians understand cancer screening statistics? A national survey of
      primary care physicians in the United States.
AB  - BACKGROUND: Unlike reduced mortality rates, improved survival rates and increased
      early detection do not prove that cancer screening tests save lives.
      Nevertheless, these 2 statistics are often used to promote screening. OBJECTIVE:
      To learn whether primary care physicians understand which statistics provide
      evidence about whether screening saves lives. DESIGN: Parallel-group, randomized
      trial (randomization controlled for order effect only), conducted by Internet
      survey. (ClinicalTrials.gov registration number: NCT00981019) SETTING: National
      sample of U.S. primary care physicians from a research panel maintained by Harris
      Interactive (79% cooperation rate). PARTICIPANTS: 297 physicians who practiced
      both inpatient and outpatient medicine were surveyed in 2010, and 115 physicians
      who practiced exclusively outpatient medicine were surveyed in 2011.
      INTERVENTION: Physicians received scenarios about the effect of 2 hypothetical
      screening tests: The effect was described as improved 5-year survival and
      increased early detection in one scenario and as decreased cancer mortality and
      increased incidence in the other. MEASUREMENTS: Physicians' recommendation of
      screening and perception of its benefit in the scenarios and general knowledge of
      screening statistics. RESULTS: Primary care physicians were more enthusiastic
      about the screening test supported by irrelevant evidence (5-year survival
      increased from 68% to 99%) than about the test supported by relevant evidence
      (cancer mortality reduced from 2 to 1.6 in 1000 persons). When presented with
      irrelevant evidence, 69% of physicians recommended the test, compared with 23%
      when presented with relevant evidence (P < 0.001). When asked general knowledge
      questions about screening statistics, many physicians did not distinguish between
      irrelevant and relevant screening evidence; 76% versus 81%, respectively, stated
      that each of these statistics proves that screening saves lives (P = 0.39). About
      one half (47%) of the physicians incorrectly said that finding more cases of
      cancer in screened as opposed to unscreened populations "proves that screening
      saves lives." LIMITATION: Physicians' recommendations for screening were based on
      hypothetical scenarios, not actual practice. CONCLUSION: Most primary care
      physicians mistakenly interpreted improved survival and increased detection with
      screening as evidence that screening saves lives. Few correctly recognized that
      only reduced mortality in a randomized trial constitutes evidence of the benefit
      of screening. PRIMARY FUNDING SOURCE: Harding Center for Risk Literacy, Max
      Planck Institute for Human Development.

PMID- 22393130
TI  - Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn disease and
      ulcerative colitis: a cohort study.
AB  - BACKGROUND: Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are anti
      inflammatory but have been linked in some studies to Crohn disease (CD) and
      ulcerative colitis (UC). OBJECTIVE: To assess the association between aspirin and
      NSAID use and incident CD and UC. DESIGN: Prospective cohort study. SETTING:
      Nurses' Health Study I. PATIENTS: 76,795 U.S. women who provided biennially
      updated data about aspirin and NSAID use. MEASUREMENTS: Incident CD and UC
      between 1990 and 2008 (outcome) and NSAID and aspirin use (exposure). RESULTS:
      123 incident cases of CD and 117 cases of UC occurred over 18 years and 1,295,317
      person-years of follow-up. Compared with nonusers, women who used NSAIDs at least
      15 days per month seemed to have increased risk for both CD (absolute difference
      in age-adjusted incidence, 6 cases per 100,000 person-years [95% CI, 0 to 13];
      multivariate hazard ratio, 1.59 [CI, 0.99 to 2.56]) and UC (absolute difference,
      7 cases per 100,000 person-years [CI, 1 to 12]; multivariate hazard ratio, 1.87
      [CI, 1.16 to 2.99]). Less frequent NSAID use was not clearly associated with risk
      for CD or UC, and there was no clear association between aspirin use and disease.
      LIMITATIONS: Cohort participants were exclusively women, most of whom were white.
      Aspirin and NSAID use were self-reported. CONCLUSION: Frequent use of NSAIDs but
      not aspirin seemed to be associated with increased absolute incidence of CD and
      UC. The findings have more mechanistic than clinical implications, because the
      absolute incidence of CD or UC associated with NSAIDs was low and the increase in
      risk for CD or UC associated with NSAIDs is unlikely to alter the balance of more
      common and clinically significant risks and benefits associated with these
      agents. PRIMARY FUNDING SOURCE: American Gastroenterological Association, IBD
      Working Group, Broad Medical Research Program, and National Institutes of Health.

PMID- 22393131
TI  - Surrogate decision makers' interpretation of prognostic information: a mixed
      methods study.
AB  - BACKGROUND: Little is known about why surrogate decision makers for patients with
      advanced illness often have overly optimistic expectations about prognosis.
      OBJECTIVE: To determine how surrogates interpret prognostic statements and to
      explore factors influencing surrogates' interpretations of grim prognostic
      information. DESIGN: Multicenter, mixed-methods study. SETTING: Intensive care
      units of 3 hospitals in San Francisco, California. PARTICIPANTS: 80 surrogates of
      critically ill patients. MEASUREMENTS: Participants recorded their interpretation
      of 16 prognostic statements using a standard probability scale. Generalized
      estimating equations were used to determine whether participants interpreted
      statements more optimistically as the expressed probability of survival
      decreased. Fifteen surrogates whose responses exhibited this trend participated
      in a semistructured interview. RESULTS: Participants' interpretations of
      prognostic statements expressing a low risk for death were relatively accurate,
      but interpretations of statements conveying a high risk for death were more
      optimistic than the actual meaning (P < 0.001; generalized estimating equation
      model). Interpretations of the statement "90% chance of surviving" did not differ
      from the actual meaning, but interpretations of "5% chance of surviving" were
      more optimistic and showed substantial variability (median, 90% [interquartile
      range, 90% to 95%; P = 0.11] vs. 15% [interquartile range, 5% to 40%; P < 0.001],
      respectively). Two main themes from the interviews explained this trend:
      surrogates' need to register optimism in the face of a poor prognosis and
      surrogates' belief that patient attributes unknown to the physician would lead to
      better-than-predicted outcomes. LIMITATION: Surrogates' interpretations were
      elicited in an experimental setting rather than during actual clinician-surrogate
      conversations. CONCLUSION: Inaccurate interpretations of physicians'
      prognostications by surrogates arise partly from optimistic biases rather than
      simply from misunderstandings. PRIMARY FUNDING SOURCE: National Heart, Lung, and
      Blood Institute.

PMID- 22393133
TI  - Screening for colorectal cancer: a guidance statement from the American College
      of Physicians.
AB  - DESCRIPTION: Colorectal cancer is the second leading cause of cancer-related
      deaths for men and women in the United States. The American College of Physicians
      (ACP) developed this guidance statement for clinicians by assessing the current
      guidelines developed by other organizations on screening for colorectal cancer.
      When multiple guidelines are available on a topic or when existing guidelines
      conflict, ACP believes that it is more valuable to provide clinicians with a
      rigorous review of the available guidelines rather than develop a new guideline
      on the same topic. METHODS: The authors searched the National Guideline
      Clearinghouse to identify guidelines developed in the United States. Four
      guidelines met the inclusion criteria: a joint guideline developed by the
      American Cancer Society, the U.S. Multi-Society Task Force on Colorectal Cancer,
      and the American College of Radiology and individual guidelines developed by the
      Institute for Clinical Systems Improvement, the U.S. Preventive Services Task
      Force, and the American College of Radiology. GUIDANCE STATEMENT 1: ACP
      recommends that clinicians perform individualized assessment of risk for
      colorectal cancer in all adults. GUIDANCE STATEMENT 2: ACP recommends that
      clinicians screen for colorectal cancer in average-risk adults starting at the
      age of 50 years and in high-risk adults starting at the age of 40 years or 10
      years younger than the age at which the youngest affected relative was diagnosed
      with colorectal cancer. GUIDANCE STATEMENT 3: ACP recommends using a stool-based
      test, flexible sigmoidoscopy, or optical colonoscopy as a screening test in
      patients who are at average risk. ACP recommends using optical colonoscopy as a
      screening test in patients who are at high risk. Clinicians should select the
      test based on the benefits and harms of the screening test, availability of the
      screening test, and patient preferences. GUIDANCE STATEMENT 4: ACP recommends
      that clinicians stop screening for colorectal cancer in adults over the age of 75
      years or in adults with a life expectancy of less than 10 years.

PMID- 22393132
TI  - What comparative effectiveness research is needed? A framework for using
      guidelines and systematic reviews to identify evidence gaps and research
      priorities.
AB  - The authors developed and tested a framework for identifying evidence gaps and
      prioritizing comparative effectiveness research by using a combination of
      clinical practice guidelines and systematic reviews. In phase 1 of the project,
      reported elsewhere, 45 clinical questions on the management of primary open-angle
      glaucoma were derived from practice guidelines and prioritized by using a 2-round
      Delphi survey of clinicians. On the basis of the clinicians' responses, 9
      questions were classified as high-priority. In phase 2, reported here, systematic
      reviews that addressed the 45 clinical questions were identified. The reviews
      were classified as at low, high, or unclear risk of bias, and evidence gaps (in
      which no systematic review was at low risk of bias) were identified. The
      following comparative effectiveness research agenda is proposed: Two of the 9
      high-priority questions require new primary research (such as a randomized,
      controlled trial) and 4 require a new systematic review. The utility and
      limitations of the framework and future adaptations are discussed.

PMID- 22393134
TI  - Screening for liver cancer: the rush to judgment.
AB  - In 2005, a professional society issued a level I recommendation to use
      ultrasonography to screen the 3 million Americans with cirrhosis for
      hepatocellular carcinoma (HCC) every 6 months. This designation was based on a
      large randomized trial from China that reported a reduction in HCC deaths from
      screening in carriers of hepatitis B surface antigen. However, besides the
      difference in population, this trial did not report all deaths, excluded patients
      after randomization, and would almost certainly have found no significant
      difference if the cluster randomization had been accounted for in the analysis.
      Misplaced confidence in the Chinese trial has led many writers to accept the
      effectiveness of HCC screening as proven, making it more difficult to conduct the
      high-quality randomized trials that are needed to ensure optimal patient care.

PMID- 22393135
TI  - Combination therapy including glucocorticoids: the new gold standard for early
      treatment in rheumatoid arthritis?

PMID- 22393136
TI  - What we don't know can hurt our patients: physician innumeracy and overuse of
      screening tests.

PMID- 22393137
TI  - Death panels.

PMID- 22393138
TI  - The emperor's new clothes.

PMID- 22393139
TI  - Can the practice of retainer medicine improve primary care?

PMID- 22393140
TI  - Can the practice of retainer medicine improve primary care?

PMID- 22393141
TI  - Can the practice of retainer medicine improve primary care?

PMID- 22393142
TI  - Can the practice of retainer medicine improve primary care?

PMID- 22393143
TI  - Can the practice of retainer medicine improve primary care?

PMID- 22393144
TI  - IgG4-related pachymeningitis: evidence of intrathecal IgG4 on cerebrospinal fluid
      analysis.

PMID- 22393145
TI  - Summaries for patients. Adding low-dose prednisone to methotrexate therapy for
      early rheumatoid arthritis.

PMID- 22393146
TI  - Summaries for patients. Surrogate decision makers' interpretation of prognostic
      information.

PMID- 22393147
TI  - Summaries for patients. Screening for colorectal cancer: a guidance statement
      from the American College of Physicians.

PMID- 22393148
TI  - In the clinic. Urinary tract infection.

PMID- 22393149
TI  - Cutting edge: dendritic epidermal gammadelta T cell ligands are rapidly and
      locally expressed by keratinocytes following cutaneous wounding.
AB  - TCR-specific activation is pivotal to dendritic epidermal T cell (DETC) function
      during cutaneous wound repair. However, DETC TCR ligands are uncharacterized, and
      little is known about their expression patterns and kinetics. Using soluble DETC
      TCR tetramers, we demonstrate that DETC TCR ligands are not constitutively
      expressed in healthy tissue but are rapidly upregulated following wounding on
      keratinocytes bordering wound edges. Ligand expression is tightly regulated, with
      downmodulation following DETC activation. Early inhibition of TCR-ligand
      interactions using DETC TCR tetramers delays wound repair in vivo, highlighting
      DETC as rapid responders to injury. To our knowledge, this is the first
      visualization of DETC TCR ligand expression, which provides novel information
      about how ligand expression impacts early stages of DETC activation and wound
      repair.

PMID- 22393150
TI  - Characterization of Ly108 in the thymus: evidence for distinct properties of a
      novel form of Ly108.
AB  - Ly108 (CD352) is a member of the signaling lymphocyte activation molecule (SLAM)
      family of receptors that signals through SLAM-associated protein (SAP), an SH2
      domain protein that can function by the recruitment of Src family kinases or by
      competition with phosphatases. Ly108 is expressed on a variety of hematopoietic
      cells, with especially high levels on developing thymocytes. We find that Ly108
      is constitutively tyrosine phosphorylated in murine thymi in a SAP- and Fyn
      kinase-dependent manner. Phosphorylation of Ly108 is rapidly lost after thymocyte
      disaggregation, suggesting dynamic contact-mediated regulation of Ly108. Similar
      to recent reports, we find at least three isoforms of Ly108 mRNA and protein in
      the thymus, which are differentially expressed in the thymi of C57BL/6 and 129S6
      mice that express the lupus-resistant and lupus-prone haplotypes of Ly108,
      respectively. Notably, the recently described novel isoform Ly108-H1 is not
      expressed in mice having the lupus-prone haplotype of Ly108, but is expressed in
      C57BL/6 mice. We further provide evidence for differential phosphorylation of
      these isoforms; the novel Ly108-H1does not undergo tyrosine phosphorylation,
      suggesting that it functions as a decoy isoform that contributes to the reduced
      overall phosphorylation of Ly108 seen in C57BL/6 mice. Our study suggests that
      Ly108 is dynamically regulated in the thymus, shedding light on Ly108 isoform
      expression and phosphorylation.

PMID- 22393151
TI  - Distinct APCs explain the cytokine bias of alpha-galactosylceramide variants in
      vivo.
AB  - alpha-Galactosylceramide represents a new class of vaccine adjuvants and
      immunomodulators that stimulate NKT cells to secrete Th1 and Th2 cytokines.
      Synthetic variants with short or unsaturated acyl chains exhibit a striking Th2
      bias in vivo but no evidence of defect in TCR signaling or stimulation of NKT
      cells in vitro. Using cd1d1(fl/fl) mice, we demonstrated that distinct APC types
      explained the cytokine bias in vivo. Whereas NKT stimulation by alpha
      Galactosylceramide required CD1d expression by dendritic cells (DCs),
      presentation of the Th2 variants was promiscuous and unaffected by DC-specific
      ablation of CD1d. This DC-independent stimulation failed to activate the feedback
      loop between DC IL-12 and NK cell IFN-gamma, explaining the Th2 bias. Conversely,
      forced presentation of the Th2 variants by DC induced high IL-12. Thus, lipid
      structural variations that do not alter TCR recognition can activate distinct Th1
      or Th2 cellular networks by changing APC targeting in vivo.

PMID- 22393152
TI  - Soluble CD23 controls IgE synthesis and homeostasis in human B cells.
AB  - CD23, the low-affinity receptor for IgE, exists in membrane and soluble forms.
      Soluble CD23 (sCD23) fragments are released from membrane (m)CD23 by the
      endogenous metalloprotease a disintegrin and metalloprotease 10. When purified
      tonsil B cells are incubated with IL-4 and anti-CD40 to induce class switching to
      IgE in vitro, mCD23 is upregulated, and sCD23 accumulates in the medium prior to
      IgE synthesis. We have uncoupled the effects of mCD23 cleavage and accumulation
      of sCD23 on IgE synthesis in this system. We show that small interfering RNA
      inhibition of CD23 synthesis or inhibition of mCD23 cleavage by an a disintegrin
      and metalloprotease 10 inhibitor, GI254023X, suppresses IL-4 and anti-CD40
      stimulated IgE synthesis. Addition of a recombinant trimeric sCD23 enhances IgE
      synthesis in this system. This occurs even when endogenous mCD23 is protected
      from cleavage by GI254023X, indicating that IgE synthesis is positively
      controlled by sCD23. We show that recombinant trimeric sCD23 binds to cells
      coexpressing mIgE and mCD21 and caps these proteins on the B cell membrane.
      Upregulation of IgE by sCD23 occurs after class-switch recombination, and its
      effects are isotype-specific. These results suggest that mIgE and mCD21 cooperate
      in the sCD23-mediated positive regulation of IgE synthesis on cells committed to
      IgE synthesis. Feedback regulation may occur when the concentration of secreted
      IgE becomes great enough to allow binding to mCD23, thus preventing further
      release of sCD23. We interpret these results with the aid of a model for the
      upregulation of IgE by sCD23.

PMID- 22393153
TI  - Inhibition of epidermal growth factor receptor tyrosine kinase ameliorates
      collagen-induced arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune synovitis characterized by the
      formation of pannus and the destruction of cartilage and bone in the synovial
      joints. Although immune cells, which infiltrate the pannus and promote
      inflammation, play a prominent role in the pathogenesis of RA, other cell types
      also contribute. Proliferation of synovial fibroblasts, for example, underlies
      the formation of the pannus, while proliferation of endothelial cells results in
      neovascularization, which supports the growth of the pannus by supplying it with
      nutrients and oxygen. The synovial fibroblasts also promote inflammation in the
      synovium by producing cytokines and chemokines. Finally, osteoclasts cause the
      destruction of bone. In this study, we show that erlotinib, an inhibitor of the
      tyrosine kinase epidermal growth factor receptor (EGFR), reduces the severity of
      established collagen-induced arthritis, a mouse model of RA, and that it does so
      by targeting synovial fibroblasts, endothelial cells, and osteoclasts. Erlotinib
      induced attenuation of autoimmune arthritis was associated with a reduction in
      number of osteoclasts and blood vessels, and erlotinib inhibited the formation of
      murine osteoclasts and the proliferation of human endothelial cells in vitro.
      Erlotinib also inhibited the proliferation and cytokine production of human
      synovial fibroblasts in vitro. Moreover, EGFR was highly expressed and activated
      in the synovium of mice with collagen-induced arthritis and patients with RA.
      Taken together, these findings suggest that EGFR plays a central role in the
      pathogenesis of RA and that EGFR inhibition may provide benefits in the treatment
      of RA.

PMID- 22393154
TI  - Pig bone marrow-derived macrophages resemble human macrophages in their response
      to bacterial lipopolysaccharide.
AB  - Mouse bone marrow-derived macrophages (BMDM) grown in M-CSF (CSF-1) have been
      used widely in studies of macrophage biology and the response to TLR agonists. We
      investigated whether similar cells could be derived from the domestic pig using
      human rCSF-1 and whether porcine macrophages might represent a better model of
      human macrophage biology. Cultivation of pig bone marrow cells for 5-7 d in
      presence of human rCSF-1 generated a pure population of BMDM that expressed the
      usual macrophage markers (CD14, CD16, and CD172a), were potent phagocytic cells,
      and produced TNF in response to LPS. Pig BMDM could be generated from bone marrow
      cells that had been stored frozen and thawed so that multiple experiments can be
      performed on samples from a single animal. Gene expression in pig BMDM from
      outbred animals responding to LPS was profiled using Affymetrix microarrays. The
      temporal cascade of inducible and repressible genes more closely resembled the
      known responses of human than mouse macrophages, sharing with humans the
      regulation of genes involved in tryptophan metabolism (IDO, KYN),
      lymphoattractant chemokines (CCL20, CXCL9, CXCL11, CXCL13), and the vitamin D3
      converting enzyme, Cyp27B1. Conversely, in common with published studies of human
      macrophages, pig BMDM did not strongly induce genes involved in arginine
      metabolism, nor did they produce NO. These results establish pig BMDM as an
      alternative tractable model for the study of macrophage transcriptional control.

PMID- 22393155
TI  - MHC class Ib-restricted CD8 T cells differ in dependence on CD4 T cell help and
      CD28 costimulation over the course of mouse polyomavirus infection.
AB  - We recently identified a protective MHC class Ib-restricted CD8 T cell response
      to infection with mouse polyomavirus. These CD8 T cells recognize a peptide from
      aa 139-147 of the VP2 viral capsid protein bound to the nonpolymorphic H-2Q9
      molecule, a member of the Qa-2 family of beta(2)m-associated MHC class Ib
      molecules. Q9:VP2.139-specific CD8 T cells exhibit an unusual inflationary
      response characterized by a gradual expansion over 3 mo followed by a stable
      maintenance phase. We previously demonstrated that Q9:VP2.139-specific CD8 T
      cells are dependent on Ag for expansion, but not for long-term maintenance. In
      this study, we tested the hypothesis that the expansion and maintenance
      components of the Q9:VP2.139-specific T cell response are differentially
      dependent on CD4 T cell help and CD28 costimulation. Depletion of CD4(+) cells
      and CD28/CD40L blockade impaired expansion of Q9:VP2.139-specific CD8 T cells,
      and intrinsic CD28 signaling was sufficient for expansion. In contrast, CD4 T
      cell insufficiency, but not CD28/CD40L blockade, resulted in a decline in
      frequency of Q9:VP2.139-specific CD8 T cells during the maintenance phase. These
      results indicate that the Q9:VP2.139-specific CD8 T cell response to mouse
      polyomavirus infection depends on CD4 T cell help and CD28 costimulation for
      inflationary expansion, but only on CD4 T cell help for maintenance.

PMID- 22393156
TI  - A dissociated glucocorticoid receptor modulator reduces airway
      hyperresponsiveness and inflammation in a mouse model of asthma.
AB  - The glucocorticoid receptor (GR) is a transcription factor able to support either
      target gene activation via direct binding to DNA or gene repression via
      interfering with the activity of various proinflammatory transcription factors.
      An improved therapeutic profile for combating chronic inflammatory diseases has
      been reported through selectively modulating the GR by only triggering its
      transrepression function. We have studied in this paper the activity of Compound
      A (CpdA), a dissociated GR modulator favoring GR monomer formation, in a
      predominantly Th2-driven asthma model. CpdA acted similarly to the glucocorticoid
      dexamethasone (DEX) in counteracting OVA-induced airway hyperresponsiveness,
      recruitment of eosinophils, dendritic cells, neutrophils, B and T cells, and
      macrophages in bronchoalveolar lavage fluid, lung Th2, Tc2, Th17, Tc17, and mast
      cell infiltration, collagen deposition, and goblet cell metaplasia. Both CpdA and
      DEX inhibited Th2 cytokine production in bronchoalveolar lavage as well as
      nuclear translocation of NF-kappaB and its subsequent recruitment onto the
      IkappaBalpha promoter in the lung. By contrast, DEX but not CpdA induces
      expression of the GR-dependent model gene MAPK phosphatase 1 in the lung,
      confirming the dissociative action of CpdA. Mechanistically, we demonstrate that
      CpdA inhibited IL-4-induced STAT6 translocation and that GR is essential for CpdA
      to mediate chemokine repression. In conclusion, we clearly show in this study the
      anti-inflammatory effect of CpdA in a Th2-driven asthma model in the absence of
      transactivation, suggesting a potential therapeutic benefit of this strategy.

PMID- 22393157
TI  - Extracellular superoxide dismutase inhibits innate immune responses and clearance
      of an intracellular bacterial infection.
AB  - Reactive oxygen species and reactive nitrogen species play important roles during
      immune responses to bacterial pathogens. Extracellular superoxide dismutase
      (ecSOD) regulates extracellular concentrations of reactive oxygen species and
      reactive nitrogen species and contributes to tissue protection during
      inflammatory insults. The participation of ecSOD in immune responses seems
      therefore intuitive, yet is poorly understood. In the current study, we used mice
      with varying levels of ecSOD activity to investigate the involvement of this
      enzyme in immune responses against Listeria monocytogenes. Surprisingly, our data
      demonstrate that despite enhanced neutrophil recruitment to the liver, ecSOD
      activity negatively affected host survival and bacterial clearance. Increased
      ecSOD activity was accompanied by decreased colocalization of neutrophils with
      bacteria, as well as increased neutrophil apoptosis, which reduced overall and
      neutrophil-specific TNF-alpha production. Liver leukocytes from mice lacking
      ecSOD produced equivalent NO. compared with liver leukocytes from mice expressing
      ecSOD. However, during infection, there were higher levels of peroxynitrite
      (NO(3).(-)) in livers from mice lacking ecSOD compared with livers from mice
      expressing ecSOD. Neutrophil depletion studies revealed that high levels of ecSOD
      activity resulted in neutrophils with limited protective capacity, whereas
      neutrophils from mice lacking ecSOD provided superior protection compared with
      neutrophils from wild-type mice. Taken together, our data demonstrate that ecSOD
      activity reduces innate immune responses during bacterial infection and provides
      a potential target for therapeutic intervention.

PMID- 22393158
TI  - Influence of ablative margin on local tumor progression and survival in patients
      with HCC <=4 cm after laser ablation.
AB  - BACKGROUND: Ablation of the normal hepatic parenchyma surrounding the tumor
      (ablative margin [AM]) is necessary to prevent local tumor progression. PURPOSE:
      To assess the prognostic value of the ablative margin in patients with HCC <=4 cm
      treated with US-guided laser ablation. MATERIAL AND METHODS: A cohort of 116
      patients (53 women and 63 men, age range 42-82 years) with 132 HCC nodules <=4 cm
      completely ablated by US-guided laser ablation was retrospectively analyzed.
      Rates of local tumor progression were compared using different ablative margin
      cut-offs (>=2.5, 5.0, 7.5, and 10.0 mm). Survival probability curves were
      obtained with the Kaplan-Meier method. RESULTS: The mean period of follow-up was
      42 months (range 3-114 months). Local tumor progression was identified in 24 out
      of 132 lesions (18%), with an average time to progression of 24 months (range 6
      36 months). A significant difference in local tumor progression was observed only
      if the ablative margin was >=7.5 mm (7% vs. 23%, P = 0.020). Survival curves of
      patients with or without an ablative margin >=7.5 mm were not different (P =
      0.665; mean survival time 43.8 +/- 3.1 and 46.8 +/- 6.1 for an AM < or >=7.5 mm,
      respectively). CONCLUSION: An ablative margin >=7.5 mm turned out to be useful in
      preventing local tumor progression but did not affect long-term survival in
      patients with HCC <=4 cm treated with laser ablation.

PMID- 22393159
TI  - Sequential combination treatment (arterial embolization and percutaneous
      radiofrequency ablation) of inoperable renal cell carcinoma: single-center pilot
      study.
AB  - BACKGROUND: Potential drawbacks of percutaneous radiofrequency ablation (RFA) for
      renal cell carcinoma (RCC) include local recurrence after RFA due to a limited
      ablation area, massive hemorrhage induced by kidney puncture, and difficulty in
      visualizing the tumor at CT-guided puncture. PURPOSE: To evaluate retrospectively
      the technical success, effectiveness, and complications elicited in patients with
      unresectable RCC following single-session sequential combination treatment
      consisting of renal arterial embolization followed by RFA. MATERIAL AND METHODS:
      Ten patients (12 RCCs) who were not candidates for surgery were included in this
      pilot study. All tumors ranged from 18-66 mm in size (mean 31 +/- 3.9 mm), and
      were percutaneously ablated several hours after embolization of the tumor vessels
      with iodized oil and gelatin sponges. We evaluated the technical success,
      effectiveness, effect on renal function, and complications of this treatment.
      Effectiveness was judged on CT and/or MR images obtained every three months after
      RFA. The effect on renal function was assessed based on the creatinine level and
      glomerular filtration rate (GFR) before, one week, and three months after the
      procedure. RESULTS: Renal arterial embolization followed by percutaneous RFA was
      technically successful in all patients. On contrast CT and/or MR images obtained
      one week and three months after RFA we observed necrosis in the embolized segment
      of all RCCs. There were no major complications during and after the procedure.
      All patients reported tolerable pain and a burning sensation during RFA. After
      the procedure, five patients (50%) experienced back pain, one each manifested
      fluid collection, subcapsular hematomas, hematuria, or nausea. There were no
      instances of recurrence during a mean follow-up period of 47 +/- 3.8 months. We
      noted no significant difference in serum creatinine and GFR before and after
      treatment. CONCLUSION: Our pilot study suggests that sequential combination
      treatment by renal arterial embolization followed by percutaneous RFA is feasible
      in patients with inoperable RCC. The treatment complications were acceptable and
      excellent effects were obtained.

PMID- 22393160
TI  - Evaluation of middle cerebral artery stents using multidetector row CT
      angiography in vivo study: comparison of the three different kernels.
AB  - BACKGROUND: There are very few reports assessing middle cerebral artery (MCA)
      stents using multidetector computed tomography (MDCT). PURPOSE: To assess MCA
      stents using multidetector CT angiography (CTA) in vivo evaluation: the
      differences in the CTA results according to the three different kernels. MATERIAL
      AND METHODS: We retrospectively evaluated 27 MCA stents from 26 patients who
      underwent CTA with 16- and 64-slice MDCT after percutaneous transluminal
      angioplasty and stenting (PTAS). By CTA, using medium-smooth kernel (B30), medium
      sharp kernel (B50), and sharp kernel (B60), the lumen diameter, artificial
      luminal narrowing (ALN), and subjective visibility score of the stented vessels
      were evaluated. The subjective visibility score ranged from 1 (poor quality) to 5
      (excellent) using a five-point scale. RESULTS: There were excellent inter
      observer agreements for the lumen diameter measurements (P < 0.001). The mean
      diameter of the stented vessels was 2.10 +/- 0.31 mm on digital subtraction
      angiography (DSA), 0.93 +/- 0.20 mm on CTA using B30, 1.18 +/- 0.27 mm on CTA
      using B50, and 1.29 +/- 0.29 mm on CTA using B60. The mean ALN was 55.7 +/- 6.0%
      on CTA using B30, 43.8 +/- 7.5% on CTA using B50, and 38.7 +/- 8.3% on CTA using
      B60. CTA with higher kernels had a smaller ALN than images with smaller kernels.
      The median subjective visibility score on the CTA using B50 was 3, which was
      higher than for the other kernels. The differences in the lumen diameter, ALN,
      and the subjective visibility score of the stented vessels on CTA using the three
      different kernels was statistically significant (P < 0.001). CONCLUSION: The
      sharp kernel was better to assess the lumen diameter and ALN, but was inferior to
      the medium-sharp kernel for in-stent evaluation due to high image-to-noise. CTA
      with medium-sharp kernel showed good lumen visibility and acceptable ALN for MCA
      stents. This could therefore be a non-invasive, readily applicable clinical
      method for assessing MCA stent patency after stent placement.

PMID- 22393161
TI  - OxLDL-targeted iron oxide nanoparticles for in vivo MRI detection of perivascular
      carotid collar induced atherosclerotic lesions in ApoE-deficient mice.
AB  - Atherosclerotic disease is a leading cause of morbidity and mortality in
      developed countries, and oxidized LDL (OxLDL) plays a key role in the formation,
      rupture, and subsequent thrombus formation in atherosclerotic plaques. In the
      current study, anti-mouse OxLDL polyclonal antibody and nonspecific IgG antibody
      were conjugated to polyethylene glycol-coated ultrasmall superparamagnetic iron
      oxide (USPIO) nanoparticles, and a carotid perivascular collar model in
      apolipoprotein E-deficient mice was imaged at 7.0 Tesla MRI before contrast
      administration and at 8 h and 24 h after injection of 30 mg Fe/kg. The results
      showed MRI signal loss in the carotid atherosclerotic lesions after
      administration of targeted anti-OxLDL-USPIO at 8 h and 24 h, which is consistent
      with the presence of the nanoparticles in the lesions. Immunohistochemistry
      confirmed the colocalization of the OxLDL/macrophages and iron oxide
      nanoparticles. The nonspecific IgG-USPIO, unconjugated USPIO nanoparticles, and
      competitive inhibition groups had limited signal changes (p < 0.05). This report
      shows that anti-OxLDL-USPIO nanoparticles can be used to directly detect OxLDL
      and image atherosclerotic lesions within 24 h of nanoparticle administration and
      suggests a strategy for the therapeutic evaluation of atherosclerotic plaques in
      vivo.

PMID- 22393162
TI  - MEG3 noncoding RNA: a tumor suppressor.
AB  - Maternally expressed gene 3 (MEG3) is an imprinted gene belonging to the
      imprinted DLK1-MEG3 locus located at chromosome 14q32.3 in humans. Its mouse
      ortholog, Meg3, also known as gene trap locus 2 (Gtl2), is located at distal
      chromosome 12. The MEG3 gene encodes a long noncoding RNA (lncRNA) and is
      expressed in many normal tissues. MEG3 gene expression is lost in an expanding
      list of primary human tumors and tumor cell lines. Multiple mechanisms contribute
      to the loss of MEG3 expression in tumors, including gene deletion, promoter
      hypermethylation, and hypermethylation of the intergenic differentially
      methylated region. Re-expression of MEG3 inhibits tumor cell proliferation in
      culture and colony formation in soft agar. This growth inhibition is partly the
      result of apoptosis induced by MEG3. MEG3 induces accumulation of p53 (TP53)
      protein, stimulates transcription from a p53-dependent promoter, and selectively
      regulates p53 target gene expression. Maternal deletion of the Meg3 gene in mice
      results in skeletal muscle defects and perinatal death. Inactivation of Meg3
      leads to a significant increase in expression of angiogenesis-promoting genes and
      microvessel formation in the brain. These lines of evidence strongly suggest that
      MEG3 functions as a novel lncRNA tumor suppressor.

PMID- 22393163
TI  - 1,25-Dihydroxyvitamin D(3) and extracellular inorganic phosphate activate mitogen
      activated protein kinase pathway through fibroblast growth factor 23 contributing
      to hypertrophy and mineralization in osteoarthritic chondrocytes.
AB  - Hypertrophy and impaired mineralization are two processes closely associated with
      osteoarthritis (OA). 1,25-dihydroxyvitamin D(3) (1a,25(OH)(2)D(3)) and inorganic
      phosphate (Pi) are two important factors that are implicated in calcium and
      phosphate homeostasis of bone metabolism and both can be regulated by the
      circulating phosphaturic factor fibroblast growth factor 23 (FGF23). The
      objective of this study was to investigate the role of 1a,25(OH)(2)D(3) and Pi
      and the molecular mechanism through which they contribute to hypertrophy and
      mineralization in human osteoarthritic chondrocytes. For this purpose, primary
      human chondrocytes were obtained from articular cartilage which was collected
      after total knee replacement surgery in OA patients. FGF23, fibroblast growth
      factor receptor 1c (FGFR1c), vitamin D(3) receptor (VDR), and phosphate inorganic
      transporter-1 and -2 (PiT-1 and PiT-2) expression levels were evaluated and found
      to be significantly higher in OA chondrocytes compared with normal. In addition,
      we observed that the binding of FGF23 to FGFR1c was stronger in OA chondrocytes
      compared  with normal. Chromatin immunoprecipitation (ChIP) assay revealed, for
      the first time, the presence of two vitamin D response elements (VDREs) in the
      FGF23 promoter. Treatment of normal chondrocytes with 1a,25(OH)(2)D(3) or Pi
      resulted in significant up-regulation of VDR, FGF23, PiT-1, PiT-2 mRNA and
      protein levels, extracellular signal-regulated kinases 1/2 (ERK1/2)
      phosphorylation and induction of hypertrophy markers collagen type X (COL10A1),
      osteopontin (OPN), osteocalcin (OC), catabolic markers metalloproteinase-13 (MMP
      13) and the apoptotic marker caspase-9. Furthermore, VDR silencing in OA
      chondrocytes negatively regulated FGF23, COL10A1, OPN, OC, MMP-13 and caspase-9
      expressions and ERK1/2 phosphorylation. Finally, combined VDR silencing and PiT
      1, PiT-2 inhibition in OA chondrocytes resulted in additive down-regulation of
      FGF23 expression, ERK1/2 activation and COL10A1, OPN, OC, MMP-13 and caspase-9
      expression levels. We propose that 1a,25(OH)(2)D(3) and Pi act synergistically
      through FGF23 signaling and ERK1/2 phosphorylation contributing to late
      hypertrophic events and impaired mineralization in osteoarthritic chondrocytes.

PMID- 22393164
TI  - CD82 expression alters with human endometrial cycles and affects the uterine
      endometrial receptivity in vitro.
AB  - Embryo implantation is a process that requires both temporal and spatial
      synchronization of the uterine endometrium and the embryo, and the endometrium
      becomes receptive to the embryo during the window of implantation. Although the
      expression patterns of many implantation-related molecules change dynamically
      during this process, the impact of CD82 on endometrial receptivity has not been
      elucidated. By immunohistochemical staining, we found that CD82 levels rose from
      the proliferative phase to the secretory phase in human endometrium.
      Specifically, the highest level appeared in mid- and late-secretory phases.
      Consistently, RL95-2 cells, representative of high-receptive endometrial
      epithelium, expressed higher levels of CD82 than did HEC-1A cells, which are
      representative of low-receptive endometrial epithelium, as detected by reverse
      transcription-polymerase chain reaction, Western blot and immunofluorescence.
      Furthermore, progesterone up-regulated the expression of CD82 in both epithelial
      cell lines. Down-regulation of CD82 in RL95-2 cells by either CD82 siRNA
      transfection or treatment with a CD82 antibody significantly decreased the
      adhesion of human embryonic JAR cells to RL95-2 cell monolayers (P < 0.01) and
      inhibited the phosphorylation of focal adhesion kinase (FAK). In contrast, up
      regulation of CD82 in HEC-1A cells by CD82 cDNA transfection promoted embryonic
      JAR cell adhesion to HEC-1A monolayers (P < 0.05) and activated the
      phosphorylation of FAK. In conclusion, the expression of CD82 increases in
      endometrial tissues during the window of embryo implantation, CD82 expression
      affects endometrial receptivity of the uterine epithelial cells in vitro, and the
      FAK signaling pathway may be involved in this phenomenon. The correlation between
      CD82 and endometrial receptivity suggests that CD82 may serve as a potential
      marker of endometrial function.

PMID- 22393165
TI  - Agaricus bisporus lectins mediates islet beta-cell proliferation through
      regulation of cell cycle proteins.
AB  - This study was designed to determine the therapeutic effect of Agaricus bisporus
      lectins (ABL) by the regeneration of beta-cells in mice following 70% partial
      pancreatectomy (PPx), and to explore the mechanisms of ABL-induced beta-cell
      proliferation. Adult C57BL/6J mice were subjected to a 70% PPx operation or a
      sham operation, and mice received 10 mg/kg body weight of ABL or saline
      immediately after surgery. Blood glucose concentrations and insulin secretion
      levels were measured. To determine the growth rates of beta-cells and duct cells,
      immunohistological analysis of pancreatic tissues was performed. Key cell cycle
      proteins and beta-cell specific genes were measured by realtime polymerase chain
      reaction, Western blotting and immunohistological staining. In this study, a
      significant decrease in blood glucose concentrations, increase in glucose
      tolerance and expanded beta-cell mass were observed in the ABL-treated mice. At
      the same time, after ABL treatment, increased beta-cell proliferation rates were
      observed. Further studies on the expression of cyclin D1, cyclin D2 and Cdk4
      demonstrated that these genes were significantly up-regulated in the ABL-treated
      mice. Meanwhile, Cdk4 activity was also enhanced. Moreover, the expression of PDX
      1 (pancreatic and duodenal homeobox 1), Ngn3 (neurogenin 3), insulin, GLUT-1
      (glucose transporter 1) and glucokinase was also increased in the ABL-treated
      mice. These findings demonstrate that ABL administration could partially reverse
      the impaired beta-cell growth potential by regulating cell cycle proteins.
      Induction of islet beta-cell proliferation by ABL suggests the therapeutic
      potential in preventing and/or treating diabetes.

PMID- 22393166
TI  - Effect of genetic variation in LRRTM3 on risk of Alzheimer disease.
AB  - OBJECTIVE: To explore the role of leucine-rich repeat transmembrane 3 (LRRTM3) in
      late-onset Alzheimer disease (AD) by independent genetic epidemiologic and
      functional studies. METHODS: First, we explored associations between LRRTM3
      single-nucleotide polymorphisms and AD in the National Institute on Aging Late
      Onset Alzheimer's Disease case-control data set (993 patients and 884 control
      subjects) and a cohort of Caribbean Hispanics (549 patients and 544 controls)
      using single-marker and haplotype analyses. Then we explored the effect of LRRTM3
      small-hairpin RNAs on amyloid precursor protein processing. RESULTS: One single
      nucleotide polymorphism in the promoter region (rs16923760; C allele: odds ratio,
      -0.74, P=.03), and a block of 4 single-nucleotide polymorphisms in intron 2
      (rs1925608, C allele: 0.84, P=.04; rs7082306, A allele: 0.75, P=.04; rs1925609, T
      allele: 1.2, P=.03; and rs10997477, T allele: 0.88, P=.05) were associated with
      AD in the National Institute on Aging Late-Onset Alzheimer's Disease data set or
      the Caribbean Hispanic data set. The corresponding haplotypes were also
      associated with AD risk (.01 < P < .05). In addition, LRRTM3 knockdown with small
      hairpin RNAs caused a significant decrease in amyloid precursor protein
      processing (P < .05 to P < .01) compared with the scrambled small-hairpin RNA
      condition. CONCLUSIONS: These complementary findings support the notions that
      genetic variation in LRRTM3 is associated with AD risk and that LRRTM3 may
      modulate gamma-secretase processing of amyloid precursor protein. Additional
      studies are needed to determine whether the specific alleles associated with
      differential risk for AD indeed confer this risk through an effect of LRRTM3
      expression levels that in turn modulates amyloid precursor protein processing.

PMID- 22393167
TI  - Preservation of neurons of the nucleus basalis in subcortical ischemic vascular
      disease.
AB  - OBJECTIVE: To investigate loss of neurons in the nucleus basalis (NB) of Meynert
      in patients with subcortical ischemic vascular disease (SIVD) compared with
      healthy controls, patients with Alzheimer disease (AD), and patients with mixed
      AD and SIVD. DESIGN: Autopsied cases drawn from a longitudinal observational
      study of patients with SIVD, patients with AD, and healthy controls. SETTING:
      Multi center, university-affiliated, program project neuropathology core.
      PATIENTS: Patients with pathologically defined SIVD (n = 16), AD (n = 20), and
      mixed AD and SIVD (n = 10) and healthy controls matched by age and educational
      level (n = 17) were studied. MAIN OUTCOME MEASURES: The NB neuronal cell counts
      in each group and their correlation with the extent of magnetic resonance imaging
      white matter lesions and Clinical Dementia Rating (CDR) scores closest to death.
      RESULTS: No significant loss of neurons was found in SIVD patients compared with
      age-matched controls in contrast to the AD and mixed groups, who had significant
      neuronal loss. A significant inverse correlation between NB neurons and CDR
      scores was found in the AD group but not in the SIVD and mixed groups. The NB
      cell counts were not correlated with either the extent of white matter lesions or
      cortical gray matter volume in the SIVD or AD groups. CONCLUSIONS: These findings
      inveigh against primary loss of cholinergic neurons in SIVD patients but do not
      rule out the possibility of secondary cholinergic deficits due to disruptions of
      cholinergic projections to cerebral cortex.

PMID- 22393168
TI  - Eight-and-a-half syndrome: a rare pontine neuro-ophthalmologic syndrome.

PMID- 22393169
TI  - Alterations in brain transition metals in Huntington disease: an evolving and
      intricate story.
AB  - BACKGROUND: Aberrant accumulation of transition metals in the brain may have an
      early and important role in the pathogenesis of several neurodegenerative
      disorders, including Huntington disease (HD). OBJECTIVE: To comprehensively
      evaluate and validate the distribution of metal deposition in the brain using
      advanced magnetic resonance imaging methods from the premanifest through
      symptomatic stages of HD. DESIGN: Observational study. SETTING: University
      imaging center. PARTICIPANTS: Twenty-eight HD expanded gene carriers, 34 patients
      with symptomatic HD, and 56 age- and sex-matched healthy control subjects were
      included in the study. INTERVENTIONS: Participants underwent magnetic resonance
      imaging for the quantification of the phase evolution of susceptibility-weighted
      images. MAIN OUTCOME MEASURES: To verify the identity of the metals responsible
      for the changes in the phase evolution of the susceptibility signal in the brain
      and to assess correlations with systemic levels. Inductively coupled plasma mass
      spectrometry was used to measure transition metal concentrations in postmortem
      brains. RESULTS: In the basal ganglia, progressive increases in the phase
      evolution were found in HD, beginning in premanifest individuals who were far
      from expected onset and increasing with proximity to expected onset and
      thereafter. Increases in the cerebral cortex were regionally selective and
      present only in symptomatic HD. Increases were verified by excessive deposition
      of brain iron, but a complex alteration in other transition metals was found.
      CONCLUSION: An important and early role of altered metal homeostasis is suggested
      in the pathogenesis of HD.

PMID- 22393170
TI  - A serine synthesis defect presenting with a Charcot-Marie-Tooth-like
      polyneuropathy.
AB  - BACKGROUND: Serine synthesis defects, characterized by developmental delay and
      seizures, have been described in children. OBJECTIVE: To describe a case of
      serine synthesis defect due to 3-phosphoglycerate dehydrogenase deficiency in an
      adult with prominent chronic polyneuropathy. DESIGN: Case report. SETTING:
      Neurologic referral center. PATIENT: A 31-year-old man with congenital cataracts,
      mild psychomotor retardation, slight cerebellar ataxia, and chronic axonal
      sensorimotor polyneuropathy. INTERVENTIONS: Electrophysiologic, metabolic, and
      genetic testing and treatment with oral L-serine. MAIN OUTCOME MEASURES: Serine
      values in plasma and cerebrospinal fluid and clinical examination. RESULTS: Amino
      acid analysis showed low serine levels in plasma and cerebrospinal fluid, and
      genetic analysis revealed 2 heterozygous mutations in the PGDH gene. Treatment
      with high-dose serine resulted in normalization of plasma serine values and
      subjective functional improvement. CONCLUSIONS: This case expands the phenotypic
      spectrum of 3-phosphoglycerate dehydrogenase deficiency. Plasma amino acid
      chromatography should be added to the list of investigations performed in
      patients with Charcot-Marie-Tooth-like polyneuropathy, especially if it is
      associated with psychomotor delay and congenital cataracts.

PMID- 22393171
TI  - Reliable change in postconcussive symptoms and its functional consequences among
      children with mild traumatic brain injury.
AB  - OBJECTIVE To examine reliable change in postconcussive symptoms and its
      functional consequences among children with mild traumatic brain injury (TBI)
      over the first year postinjury as compared with children with orthopedic
      injuries. DESIGN Prospective, longitudinal cohort. SETTING Emergency departments
      at 2 children's hospitals. PARTICIPANTS Eight- to 15-year-old children with mild
      TBI (n = 186) or orthopedic injuries (n = 99). MAIN EXPOSURE Closed-head or
      orthopedic trauma. MAIN OUTCOME MEASURES Parents rated preinjury symptoms
      retrospectively shortly after injury and postconcussive symptoms at 2 weeks and 3
      and 12 months postinjury. A regression-based approach was used to determine
      whether each child displayed reliable increases in postconcussive symptoms at
      each postinjury occasion. Health-related quality of life was assessed at 3 and 12
      months postinjury. Information regarding children's educational programming was
      collected at the initial and 12-month assessments. RESULTS Children with mild TBI
      were significantly more likely than those with orthopedic injuries to show
      reliable increases in both cognitive and somatic symptoms. Group differences in
      the likelihood of reliable increases became less common with time for somatic
      symptoms but persisted to 12 months postinjury for cognitive symptoms. Among
      children with mild TBI, reliable increases in symptoms were more common among
      children with loss of consciousness or abnormalities on neuroimaging. Reliable
      increases in symptoms were associated with significant declines in health-related
      quality of life and an increased likelihood of educational intervention.
      CONCLUSION Many children with mild TBI show reliable increases in postconcussive
      symptoms that are associated with significant functional impairment in their
      daily lives.

PMID- 22393172
TI  - Vitamin d, calcium, and dairy intakes and stress fractures among female
      adolescents.
AB  - OBJECTIVE To identify whether calcium, vitamin D, and/or dairy intakes are
      prospectively associated with stress fracture risk among female adolescents.
      DESIGN Prospective cohort study. SETTING Adolescent girls living throughout the
      United States. PARTICIPANTS A total of 6712 girls aged 9 to 15 years at baseline
      in the Growing Up Today Study, an ongoing prospective cohort study. MAIN
      EXPOSURES Dairy, calcium, and vitamin D intakes assessed by food frequency
      questionnaire every 12 to 24 months between 1996 and 2001. MAIN OUTCOME MEASURE
      Incident stress fracture that occurred between 1997 and 2004 as reported by
      mothers of the participants in 2004. Cox proportional hazards models were used to
      examine associations. RESULTS During 7 years of follow-up, 3.9% of the girls
      developed a stress fracture. Dairy and calcium intakes were unrelated to risk of
      developing a stress fracture. However, vitamin D intake was inversely related to
      stress fracture risk. The multivariable-adjusted hazard ratio of stress fracture
      for the highest vs the lowest quintile of vitamin D intake was 0.49 (95% CI, 0.24
      1.01; Ptrend = .07). We conducted a stratified analysis to estimate the
      association between vitamin D intake and stress fracture risk among girls
      participating in at least 1 h/d of high-impact activity, among whom 90.0% of the
      stress fractures occurred, and found that higher vitamin D intake predicted
      significantly lower risk of stress fracture (Ptrend = .04). CONCLUSIONS Vitamin D
      intake is associated with lower stress fracture risk among adolescent girls who
      engage in high levels of high-impact activity. Neither calcium intake nor dairy
      intake was prospectively associated with stress fracture risk.

PMID- 22393173
TI  - Concussion: time to start paying attention.

PMID- 22393174
TI  - Removal of Bovine Insulin From Cow's Milk Formula and Early Initiation of Beta
      Cell Autoimmunity in the FINDIA Pilot Study.
AB  - OBJECTIVE To test whether weaning to a bovine insulin-free cow's milk formula
      (CMF) reduces type 1 diabetes mellitus-associated autoantibodies in children at
      genetic risk. DESIGN Randomized, double-blind pilot trial (Finnish Dietary
      Intervention Trial for the Prevention of Type 1 Diabetes [FINDIA]). SETTING Three
      pediatric hospitals in Finland from May 15, 2002, to November 22, 2005.
      PARTICIPANTS A total of 1113 infants with HLA-conferred susceptibility to type 1
      diabetes were randomly assigned to receive study infant formulas; 908 children
      provided at least 1 follow-up blood sample (last follow-up, June 2009).
      INTERVENTION The CMF (n = 389), whey-based hydrolyzed formula (WHF) (n = 350), or
      whey-based FINDIA formula essentially free of bovine insulin (n = 365) during the
      first 6 months of life whenever breast milk was not available. MAIN OUTCOME
      MEASURES Primary outcome was beta-cell autoimmunity monitored at ages 3, 6, and
      12 months and then annually until age 3 years. Autoantibodies to insulin, the 65
      kDa isoform of glutamic acid decarboxylase, and the tyrosine phosphatase-related
      IA-2 molecule were screened, and islet cell autoantibodies and autoantibodies to
      zinc transporter 8 were analyzed in infants whose primary screening test results
      were positive. RESULTS In the intention-to-treat analysis, 6.3% of children in
      the CMF group, 4.9% of those in the WHF group, and 2.6% of children in the FINDIA
      group were positive for at least 1 autoantibody by age 3 years. The odds ratios
      were 0.75 (95% CI, 0.37-1.54) in the WHF group and 0.39 (0.17-0.91) in the FINDIA
      group when compared with the CMF group. In the treatment-received analysis, the
      corresponding odds ratios were 0.81 (95% CI, 0.37-1.76) and 0.23 (0.08-0.69).
      CONCLUSION In comparison with ordinary CMF, weaning to an insulin-free CMF
      reduced the cumulative incidence of autoantibodies by age 3 years in children at
      genetic risk of type 1 diabetes mellitus. TRIAL REGISTRATION clinicaltrials.gov
      Identifier: NCT01055080.

PMID- 22393175
TI  - Retinal hemorrhages in children: the role of intracranial pressure.
AB  - OBJECTIVE To evaluate the role of intracranial pressure (ICP) in the production
      of retinal hemorrhage in young children. DESIGN Review of published clinical,
      postmortem, and experimental research findings worldwide pertinent to our review
      objective. We used PubMed, MEDLINE, and Ovid Evidence-Based Medicine Reviews as
      well as references found in other published articles to conduct searches. MAIN
      EXPOSURES Increased ICP from various etiologies. MAIN OUTCOME MEASURE Hemorrhagic
      retinopathy, in particular with extension to the periphery, multiple layers, and
      too-numerous-to-count hemorrhages. The review also considers additional
      intraocular findings such as retinoschisis and perimacular folds. RESULTS In
      general, elevated ICP does not cause extensive hemorrhagic retinopathy.
      Papilledema may be associated with a small number of hemorrhages on or around the
      optic disc. There are isolated case reports that severe hyperacute ICP elevation,
      unlike the subacute pressure increase in abusive head injury, in children may
      rarely result in extensive retinal hemorrhage. These diagnoses are readily
      distinguished from child abuse. CONCLUSIONS In the absence of the few readily
      recognizable alternate scenarios, extensive retinal hemorrhage in very young
      children is not secondary to isolated elevated ICP.

PMID- 22393176
TI  - Treatment of postmenopausal vaginal atrophy with 10-MUg estradiol vaginal
      tablets.
AB  - Postmenopausal estrogen deficiency can lead to symptoms of urogenital atrophy.
      Individuals with urogenital atrophy have symptoms that include vaginal dryness,
      vaginal and vulval irritation, vaginal soreness, pain and burning during
      urination (dysuria), increased vaginal discharge, vaginal odour, vaginal
      infections, recurrent urinary tract infections, pain associated with sexual
      activity (dyspareunia) and vaginal bleeding associated with sexual activity.
      Despite the frequency and effects of vaginal atrophy symptoms, they are often
      under-reported and, consequently, under-treated. Therefore, care of a menopausal
      woman should include a physical assessment of vaginal atrophy and a dialogue
      between the physician and the patient that explores existing symptoms and their
      effect on vulvovaginal health, sexuality and quality-of-life issues. The
      development of the ultra-low-dose 10-ug estradiol vaginal tablets is in line with
      the requirements of regulatory agencies and women's health societies regarding
      the use of the lowest effective hormonal dose. Because of its effectiveness and
      safety profiles, in addition to its minimal systemic absorption, the 10-ug
      estradiol vaginal tablet can offer greater reassurance to health-care providers
      and postmenopausal women with an annual estradiol administration of only 1.14 mg.

PMID- 22393177
TI  - Alternative and complementary therapies for the menopause.
AB  - Despite a re-evaluation of risks in recent years, hormone replacement therapy is
      still surrounded by controversy. Almost 30% of women in a recent survey sought a
      natural approach to combat climacteric symptoms. Nevertheless, a large proportion
      of patients felt that they wanted a good safety profile and strong evidence base
      for treatment. This article seeks to review the evidence supporting non-hormonal
      approaches to treatment. There is only conflicting evidence at best to support
      alpha-2 agonists, e.g. clonidine and limited evidence for dihydroepiandrosterone
      and natural progesterones. There is limited randomized controlled trial data for
      gabapentin, selective norepinephrine re-uptake inhibitors (SNRIs) and selective
      serotonin re-uptake inhibitors (SSRIs), many of these studies being related to
      breast cancer patients. Of the herbal medicinal products, the largest evidence
      base rests with phytoestrogens. A Cochrane Database review looking at all types
      of phytoestrogens, e.g. red clover extracts, dietary soya and soya extracts
      concluded that there was no evidence to support improvement in climacteric
      symptoms and the meta-analysis of a 178 studies on soy products was inconsistent.
      Nevertheless, other studies disagree. Mammographic density is not affected by soy
      or phytoestrogen products and recent in vitro work shows only a weakly
      proliferative effect of soy isoflavone on breast cancer cells and evidence that
      soy isoflavone blocks the proliferative effect of estradiol on these cells. There
      are no studies looking at clinical outcome measures for cardiovascular disease
      but a number of studies looking at biochemical markers including arterial wall
      stiffness and apolipo protein B. Recent studies have also looked at the effects
      of red clover isoflavone on mood and depression, using specific depression rating
      scales. Finally, it is important to note that herbal medicinal products should
      not be used without caution. Some may produce quite marked side-effects in high
      doses and others can interact with pre-existing medication. A strategy for which
      patients are suitable for herbal medicinal products is reviewed.

PMID- 22393178
TI  - Commentary regarding recent Million Women Study critique and subsequent
      publicity.

PMID- 22393179
TI  - Preoperative risk factors for in-hospital mortality and validity of the Glasgow
      aneurysm score and Hardman index in patients with ruptured abdominal aortic
      aneurysm.
AB  - The aim of this study is to evaluate the validity of the Glasgow aneurysm score
      (GAS) and Hardman index in patients operated on because of ruptured abdominal
      aortic aneurysm (rAAA), and determining preoperative risk factors that affect in
      hospital mortality. One hundred one patients operated on to repair a rAAA within
      the last 10 years were included. The GAS and Hardman index were calculated for
      each patient separately. The relation between in-hospital mortality and the
      Hardman index and GAS was analyzed by means of the receiver-operator
      characteristic (ROC) curve. Univariate and multivariate methods of analyses were
      used to determine preoperative risk factors. Average age was 69 +/- 8, and in
      hospital mortality rate was 51.5%. Analysis of the ROC curve showed that the
      Hardman index had an area under the curve (AUC) = 0.71 (95% confidence interval
      [CI], 0.593-0.800, P = 0.0002) for predicting in-hospital mortality. The GAS had
      an AUC = 0.77 (95% CI, 0.680-0.851, P < 0.0001). The results of multivariate
      analysis revealed the presence of the following preoperative risk factors: age
      more than 63 years (odds ratio [OR], 4.4; 95% CI, 1.17-16.49, P = 0.028); loss of
      consciousness (OR, 9.33; 95% CI, 1.94-44.86, P = 0.005); creatinine higher than
      1.7 mg/dL (OR, 5.52; 95% CI, 1.92-15.85, P = 0.001); and pH lower than 7.31 (OR,
      3.77; 95% CI, 1.18-11.99, P = 0.024). In conclusion, the Hardman index and GAS
      have a significant correlation with in-hospital mortality rates. Nevertheless, a
      high score does not necessarily correspond with a definite mortality. This is why
      scoring systems could not be considered as the sole criterion for choosing
      patients for this study. Clinical experience was still the leading factor in
      deciding against or in favor of surgery.

PMID- 22393180
TI  - Effect of parental bereavement on health risk behaviors in youth: a 3-year follow
      up.
AB  - OBJECTIVE: To examine the course of health risk behaviors (HRBs) during a 3-year
      period after a parent's death in bereaved youth compared with nonbereaved youth
      (control subjects). DESIGN: A longitudinal population-based study. SETTING:
      Bereaved families were recruited through coroner records and by advertisement.
      Control families were recruited using random-digit dialing and by advertisement.
      PARTICIPANTS: Two hundred forty parentally bereaved offspring were compared with
      183 nonbereaved control offspring. MAIN EXPOSURE: Sudden parental death due to
      accident, suicide, or sudden disease-related (natural) death. MAIN OUTCOME
      MEASURES: The sum of the total number of HRBs at a clinically significant
      frequency threshold assessed 9, 21, and 33 months after the parent's death.
      RESULTS: The bereaved group showed a higher number of HRBs over time compared
      with the nonbereaved group (univariate effect sizes, 0.22-0.52; P < .04), even
      after taking into account correlates of bereavement and of HRBs, such as youth
      aggression, as well as antisocial and anxiety disorders of the deceased parent.
      CONCLUSIONS: Parental bereavement is associated with higher HRBs in youth over
      time, even after controlling for other covariates associated with bereavement and
      HRBs. Clinicians should be aware that bereaved youth may be vulnerable to HRBs.
      Further work is warranted on interventions to attenuate the negative effect of
      bereavement on HRBs.

PMID- 22393181
TI  - Effect of rotavirus vaccine on reducing acute gastroenteritis in a large
      outpatient pediatric network.
AB  - OBJECTIVES: To measure the effect of rotavirus vaccine (RVV) on acute
      gastroenteritis (AGE) managed by primary care physicians in the first 2
      rotatvirus seasons following the introduction of RVV. DESIGN: Retrospective
      cohort study. SETTING: Practice-based network composed of 33 ambulatory pediatric
      practices in Philadelphia, Pennsylvania. PARTICIPANTS: All children born from
      February 22, 2006 (date of RVV licensure), through February 29, 2008, and who
      received care at any network site. MAIN EXPOSURE: Receipt of RVV. OUTCOME
      MEASURES: The primary outcomes were AGE-related office visits, telephone calls,
      and episodes (composite outcome consisting of all visits and calls within a 10
      day period). RESULTS: Rates of AGE visits in the 2 rotavirus seasons following
      the introduction of RVV steadily decreased from 3.0 AGE visits per 100 total
      office visits in the 2005 season to 1.8 in the 2008 season. In 2007, vaccinations
      were administered to 9351 of 13 951 vaccine-eligible children (67.0%), and in
      2008, they were administered to 9958 of 10 728 (92.8%). Among RVV-immunized
      children in 2007, AGE calls and episodes were significantly reduced with vaccine
      effectiveness of 53% and 46%, respectively. No significant difference was seen
      between RVV-immunized and RVV-nonimmunized children for any outcome in 2008.
      CONCLUSIONS: Rotavirus vaccine was associated with a significant reduction in
      outpatient AGE calls and episodes among immunized children in our network in
      2007. Despite a reduction in winter AGE rates in the network, no difference was
      detected between RVV-immunized and RVV-nonimmunized children for any outcome in
      2008. Further study is needed to understand the lack of vaccine effect in 2008.

PMID- 22393182
TI  - Young adult preventive health care guidelines: there but can't be found.
AB  - OBJECTIVES: To (1) identify adolescent and adult clinical preventive services
      guidelines relevant to the young adult age group; (2) review, compare, and
      synthesize these guidelines, with emphasis on the extent to which professional
      guidelines are consistent with evidence-based guidelines developed by the US
      Preventive Services Task Force; and (3) recommend the next steps in the
      establishment and integration of preventive care guidelines for young adults.
      DESIGN: Nonexperimental: an Internet search was conducted to identify relevant
      preventive care guidelines for the young adult group. SETTING: The search
      included federal agencies and professional organizations that focus on health
      areas linked to the care of young adults or that provide health care to
      adolescents and young adults. PARTICIPANTS: National organizations, federal
      agencies, health professional associations, and medical societies. MAIN OUTCOME
      MEASURES: Preventive services guidelines for adolescents and adults that
      intersect with the age range of 18 to 26 years. RESULTS: When the ages of 18 to
      26 years are carved out of established professional guidelines across specialty
      groups, there is a broad number of recommendations, with many supported by
      sufficient evidence to receive a US Preventive Services Task Force grade of A or
      B that can inform the care of young adults. CONCLUSIONS: We recommend the
      establishment of young adult preventive health guidelines that reflect the
      current evidence-based recommendations that overlap with the young adult age
      group; we suggest clinician and health care system supports to facilitate the
      delivery of preventive services to young adults; and we emphasize prioritizing
      research in prevention areas in which sufficient evidence does not exist.

PMID- 22393183
TI  - Environmental factors in Tiny Tim's near-fatal illness.
AB  - Physicians, Dickens scholars, and historians have tried to diagnose the condition
      that affected Tiny Tim in A Christmas Carol. Leading entities include
      tuberculosis (TB), rickets, malnutrition, cerebral palsy, spinal dysraphism, and
      renal tubular acidosis. This article posits that an examination of the
      environment of London of 1820 to 1843 (when the novella was written) can provide
      important clues as to his condition. The blackened skies from burning coal, the
      crowding of people in tenements, the limited diet of the underclass, and the
      filth of London resulted in a haven for infectious diseases and rickets in
      children. Sixty percent of children in London had rickets, and nearly 50% had
      signs of TB. Tiny Tim likely had a combination of both diseases. After Ebenezer
      Scrooge's transformation, Scrooge could have ensured an improved diet, sunshine
      exposure, and possibly cod liver oil for Tiny Tim, which could have led to a
      "cure." Dickens was familiar with both rickets and TB and wrote about cod liver
      oil as a possible cure for rickets and scrofula. Improved vitamin D status can
      result in enhanced macrophage synthesis of 1,25-dihydroxyvitamin D, which
      increases the synthesis of the antimicrobial peptide cathelicidin (LL-37). This
      component of the innate immune system has strong killing properties for
      Mycobacterium tuberculosis. The combination of rickets and TB represent a
      crippling condition that could be reversed by improved vitamin D status.

PMID- 22393184
TI  - Prevalence of child mental health problems in sub-Saharan Africa: a systematic
      review.
AB  - OBJECTIVE: To assess the prevalence of child mental health problems in community
      settings in sub-Saharan Africa. DATA SOURCES: A systematic search of MEDLINE,
      EMBASE, and PsychInfo, supplemented by tracking of references from identified
      articles and personal communications with local researchers. STUDY SELECTION:
      Only community-based studies in sub-Saharan Africa that assessed the general
      psychopathology of children aged 0 to 16 years were included. For each eligible
      study, the following information was extracted: year of publication, country,
      population sampled, area type (rural or urban), sampling method and sample size
      (percentage boys), age range, assessment instrument, informant, diagnostic
      criteria, and prevalence rates of general psychopathology. MAIN OUTCOME MEASURE:
      Pooled prevalence rate of psychopathology in children, identified by
      questionnaire and, specifically, by clinical diagnostic instruments. RESULTS:
      Eleven studies met the inclusion criteria, 10 of which were included in the meta
      analysis. The 10 studies provided data for 9713 children from 6 countries, with
      substantial variation in assessment methods. Overall, 14.3% (95% CI, 13.6%-15.0%)
      of children were identified as having psychopathology. Studies using screening
      questionnaires reported higher prevalence rates (19.8%; 95% CI, 18.8%-20.7%) than
      did studies using clinical diagnostic instruments (9.5%; 8.4%-10.5%).
      CONCLUSIONS: Evidence suggests that considerable levels of mental health problems
      exist among children and adolescents in sub-Saharan Africa. One in 7 children and
      adolescents have significant difficulties, with 1 in 10 (9.5%) having a specific
      psychiatric disorder. There are clear sociodemographic correlates of
      psychopathology that may place children in areas of greatest deprivation at
      greatest risk.

PMID- 22393185
TI  - Picture of the month--a case of neonatal lupus erythematosus and associated
      hepatitis.

PMID- 22393186
TI  - Focus on preventive health care for young adults.

PMID- 22393187
TI  - The development of practical guidelines for the care of deceased children is
      perhaps a utopia?

PMID- 22393188
TI  - When a loved one dies.

PMID- 22393189
TI  - Pre-judging data: benchmarking clinical significance before study results are
      known.

PMID- 22393190
TI  - Ten years of progress in non-small cell lung cancer.

PMID- 22393191
TI  - A 66-year-old woman with newly diagnosed oligometastatic non-small cell lung
      cancer.
AB  - A 66-year-old woman presented with newly diagnosed stage IV non-small cell lung
      cancer (NSCLC) and a large adrenal metastasis. She initially had flu-like
      symptoms and dyspnea and was found to have a right upper lobe (RUL) lung nodule.
      Chest CT showed a 1.4-cm spiculated RUL lung nodule, peripheral right lung
      nodule, right perihilar mass, and 10.9-cm left adrenal mass. PET/CT showed
      enhancement of the RUL nodule, hilar mass, and left adrenal mass. She presented
      for evaluation of treatment options. This case was thought to represent an
      instance of oligometastatic stage IV NSCLC. Literature suggests that a select
      patient population with otherwise resectable disease may benefit from surgical
      resection of a lung primary and the isolated metastasis with improved survival.
      This seems to be most effective in patients who have undergone a complete staging
      evaluation with PET scan; CT of the chest, abdomen, and pelvis; and a brain MRI
      revealing T1-2, N0-1, M-oligo disease. This radical approach should be reserved
      for patients with potentially curative disease based on the staging evaluation
      and who are otherwise good surgical candidates.

PMID- 22393192
TI  - Predictive biomarkers in advance of a companion drug: ahead of their time?
AB  - Because of a surge in molecular testing capabilities concurrent with the rising
      numbers of targeted therapies in clinical development, the commercial use of
      predictive biomarkers before clinical validation is available is a topic of
      growing relevance to medical oncologists. Increasingly, patients will present
      questions about, requests for, and results from commercial biomarker tests for
      their oncologists to address. The sheer numbers of tests reaching the market,
      along with forecasted American Medical Association reforms in current procedural
      terminology coding and increasing FDA oversight of in vitro companion diagnostic
      device development, are likely to draw intense scrutiny to the regulation of
      commercial molecular testing in the near future, which will also require
      clinicians to remain abreast of the level of clinical validation of the biomarker
      tests available in practice. In addition to the direct risks of novel biomarker
      testing, including financial cost and ethical issues, the indirect risks
      encompass those associated with any clinical decision based on the biomarker test
      results. A great need exists for comprehensive and dynamic practice guidelines
      for all types of biomarker testing according to tumor type.

PMID- 22393193
TI  - Dermatofibrosarcoma protuberans.

PMID- 22393194
TI  - Mucosal melanoma of the head and neck.

PMID- 22393195
TI  - Mucosal melanoma: a clinically and biologically unique disease entity.
AB  - Mucosal melanoma (MM) is an aggressive and clinically complex malignancy made
      more challenging by its relative rarity. Because of the rarity of MM as a whole,
      and because of the unique biology and clinical challenges of MM arising from each
      anatomic location, understanding of this disease and its optimal management
      remains limited. The impact of various treatment strategies on disease control
      and survival has been difficult to assess because of the small size of most
      reported series of MM arising from any one particular site, the retrospective
      nature of most series, and the lack of a uniform comprehensive staging system for
      this disease. This article summarizes the clinical, pathologic, and molecular
      features, and the diagnostic and therapeutic considerations for the management of
      MM, underscoring the similarities and differences from cutaneous melanoma.
      Furthermore, the distinct clinical features and management implications unique to
      melanoma arising from the mucosal surfaces of the head and neck, the anorectal
      region, and the female genital tract are highlighted.

PMID- 22393196
TI  - Unanswered questions about margin recommendations for primary cutaneous melanoma.
AB  - Radical wide excision with appropriate margins based on depth of tumor invasion
      has been the standard adopted in NCCN and national clinical practice guidelines
      in oncology based on randomized controlled trial data. When carefully
      scrutinized, however, questions remain unanswered about what constitute
      appropriate margins in many frequently encountered clinical situations. In
      addition to the single characteristic of tumor depth, factors such as primary
      tumor location, histologic classification, and even specific patient
      characteristics may all contribute to risk for local recurrence, and therefore
      should potentially be considered in margin recommendations. This article
      addresses current uncertainty surrounding optimal margin status in primary
      cutaneous melanoma.

PMID- 22393197
TI  - Melanoma.

PMID- 22393198
TI  - Systemic therapy for metastatic melanoma in 2012: dawn of a new era.
AB  - The 10-year survival rate for patients with metastatic melanoma is less than 10%.
      Although surgery and radiation therapy have a role in the treatment of metastatic
      disease, systemic therapy is the mainstay of treatment for these patients. After
      decades of failed attempts to improve treatment outcomes, recent successes with
      ipilimumab and vemurafenib have ushered in a new era in systemic therapy. Both
      ipilimumab and vemurafenib are associated with significant improvements in
      overall survival of patients in randomized phase III trials, an end point that
      had proven elusive so far. These breakthroughs not only provide more treatment
      options for patients with melanoma but also spur the investigation of a new
      generation of drugs for cancer therapy in general. This article reviews both the
      current systemic treatment options for metastatic melanoma and promising
      investigational approaches.

PMID- 22393199
TI  - Controversies in the management of regional nodes in melanoma.
AB  - The surgical management of the regional lymph node basin of melanoma has
      undergone significant changes in the past 2 decades, most of which have been
      guided by prospective randomized trials. Historically, routine elective lymph
      node dissection was recommended for the management of melanoma regardless of
      clinical nodal involvement. Subsequent randomized trials failed to show a clear
      benefit for all patients, and sentinel lymph node (SLN) biopsy emerged as an
      alternative. Although the prognostic value of SLN biopsy in intermediate
      thickness melanoma is well accepted, its value for patients with thin and thick
      lesions is debated. The therapeutic advantage of removing an involved SLN, and
      the need for a completion lymph node dissection after the identification of a
      positive SLN, are areas of continued controversy. This article discusses these
      issues in the management of the regional lymph node basin in patients with
      melanoma.

PMID- 22393202
TI  - Maternal use of selective serotonin reuptake inhibitors, fetal growth, and risk
      of adverse birth outcomes.
AB  - CONTEXT: Selective serotonin reuptake inhibitors (SSRIs) are frequently
      prescribed to pregnant women, but knowledge about their unintended effects on
      child health is scarce. OBJECTIVE: To examine the effects of maternal SSRI use
      during pregnancy on fetal growth and birth outcomes. DESIGN: The study was
      embedded in the Generation R Study, a prospective population-based study from
      fetal life onward. PARTICIPANTS: Seven thousand six hundred ninety-six pregnant
      women were included. Selective serotonin reuptake inhibitor use was assessed by
      questionnaires in each trimester and verified by pharmacy records. Using
      depressive symptom scores from the Brief Symptom Inventory, 7027 pregnant mothers
      (91.3%) had no or low depressive symptoms, 570 pregnant mothers (7.4%) had
      clinically relevant depressive symptoms and used no SSRIs, and 99 pregnant
      mothers (1.3%) used SSRIs. MAIN OUTCOME MEASURES: Fetal ultrasonography was
      performed in each trimester. We determined fetal body and head growth with
      repeated assessments of body and head size. The birth outcomes studied were
      preterm birth, small for gestational age, and low birth weight. RESULTS: Fetuses
      from mothers with prenatal depressive symptoms showed reduced body growth (beta=
      4.4 g/wk; 95% CI: -6.3 to -2.4; P<.001) and head growth (beta=-0.08 mm/wk; 95%
      CI: -0.14 to -0.03; P=.003). Mothers using SSRIs during pregnancy had fewer
      depressive symptoms than mothers in the clinical symptom range. Prenatal SSRI use
      was not associated with reduced body growth but was associated with reduced fetal
      head growth (beta=-0.18 mm/wk; 95% CI: -0.32 to -0.07; P=.003). The SSRI-exposed
      children were at higher risk for preterm birth (odds ratio=2.14; 95% CI: 1.08 to
      4.25; P=.03). CONCLUSIONS: Untreated maternal depression was associated with
      slower rates of fetal body and head growth. Pregnant mothers treated with SSRIs
      had fewer depressive symptoms and their fetuses had no delay in body growth but
      had delayed head growth and were at increased risk for preterm birth. Further
      research on the implications of these findings is needed.

PMID- 22393203
TI  - Probing thalamic integrity in schizophrenia using concurrent transcranial
      magnetic stimulation and functional magnetic resonance imaging.
AB  - CONTEXT: Schizophrenia is a devastating illness with an indeterminate
      pathophysiology. Several lines of evidence implicate dysfunction in the thalamus,
      a key node in the distributed neural networks underlying perception, emotion, and
      cognition. Existing evidence of aberrant thalamic function is based on indirect
      measures of thalamic activity, but dysfunction has not yet been demonstrated with
      a causal method. OBJECTIVE: To test the hypothesis that direct physiological
      stimulation of the cortex will produce an abnormal thalamic response in
      individuals with schizophrenia. DESIGN: We stimulated the precentral gyrus with
      single-pulse transcranial magnetic stimulation (spTMS) and measured the response
      to this pulse in synaptically connected regions (thalamus, medial superior
      frontal cortex, insula) using concurrent functional magnetic resonance imaging.
      The mean hemodynamic response from these regions was fit with the sum of 2 gamma
      functions, and response parameters were compared across groups. SETTING: Academic
      research laboratory. PARTICIPANTS: Patients with schizophrenia and sex- and age
      matched psychiatrically healthy subjects were recruited from the community. MAIN
      OUTCOME MEASURE: Peak amplitude of the thalamic hemodynamic response to spTMS of
      the precentral gyrus. RESULTS: The spTMS-evoked responses did not differ between
      groups at the cortical stimulation site. Compared with healthy subjects, patients
      with schizophrenia showed a reduced response to spTMS in the thalamus (P=1.86 *
      10(-9)) and medial superior frontal cortex (P=.02). Similar results were observed
      in the insula. Sham TMS indicated that these results could not be attributed to
      indirect effects of TMS coil discharge. Functional connectivity analyses revealed
      weaker thalamus-medial superior frontal cortex and thalamus-insula connectivity
      in patients with schizophrenia compared with control subjects. CONCLUSIONS:
      Individuals with schizophrenia showed reduced thalamic activation in response to
      direct perturbation delivered to the cortex. These results extend prior work
      implicating the thalamus in the pathophysiology of schizophrenia and suggest that
      the thalamus contributes to the patterns of aberrant connectivity characteristic
      of this disease.

PMID- 22393205
TI  - Benefits from antidepressants: synthesis of 6-week patient-level outcomes from
      double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine.
AB  - CONTEXT: Some meta-analyses suggest that efficacy of antidepressants for major
      depression is overstated and limited to severe depression. OBJECTIVE: To
      determine the short-term efficacy of antidepressants for treating major
      depressive disorder in youth, adult, and geriatric populations. DATA SOURCES:
      Reanalysis of all intent-to-treat person-level longitudinal data during the first
      6 weeks of treatment of major depressive disorder from 12 adult, 4 geriatric, and
      4 youth randomized controlled trials of fluoxetine hydrochloride and 21 adult
      trials of venlafaxine hydrochloride. STUDY SELECTION: All sponsor-conducted
      randomized controlled trials of fluoxetine and venlafaxine. DATA EXTRACTION:
      Children's Depression Rating Scale-Revised scores (youth population), Hamilton
      Depression Rating Scale scores (adult and geriatric populations), and estimated
      response and remission rates at 6 weeks were analyzed for 2635 adults, 960
      geriatric patients, and 708 youths receiving fluoxetine and for 2421 adults
      receiving immediate-release venlafaxine and 2461 adults receiving extended
      release venlafaxine. DATA SYNTHESIS: Patients in all age and drug groups had
      significantly greater improvement relative to control patients receiving placebo.
      The differential rate of improvement was largest for adults receiving fluoxetine
      (34.6% greater than those receiving placebo). Youths had the largest treated vs
      control difference in response rates (24.1%) and remission rates (30.1%), with
      adult differences generally in the 15.6% (remission) to 21.4% (response) range.
      Geriatric patients had the smallest drug-placebo differences, an 18.5% greater
      rate of improvement, 9.9% for response and 6.5% for remission. Immediate-release
      venlafaxine produced larger effects than extended-release venlafaxine. Baseline
      severity could not be shown to affect symptom reduction. CONCLUSIONS: To our
      knowledge, this is the first research synthesis in this area to use complete
      longitudinal person-level data from a large set of published and unpublished
      studies. The results do not support previous findings that antidepressants show
      little benefit except for severe depression. The antidepressants fluoxetine and
      venlafaxine are efficacious for major depressive disorder in all age groups,
      although more so in youths and adults compared with geriatric patients. Baseline
      severity was not significantly related to degree of treatment advantage over
      placebo.

PMID- 22393204
TI  - Cannabinoid receptor genotype moderation of the effects of childhood physical
      abuse on anhedonia and depression.
AB  - CONTEXT: The endocannabinoid system has been implicated in stress adaptation and
      the regulation of mood in rodent studies, but few human association studies have
      examined these links and replications are limited. OBJECTIVES: To examine whether
      a synonymous polymorphism, rs1049353, in exon 4 of the gene encoding the human
      endocannabinoid receptor (CNR1) moderates the effect of self-reported childhood
      physical abuse on lifetime anhedonia and depression and to replicate this
      interaction in an independent sample. DESIGN, SETTING, AND PARTICIPANTS: Genetic
      association study in 1041 young US women with replication in an independent
      Australian sample of 1428 heroin-dependent individuals as cases and 506
      participants as neighborhood controls. MAIN OUTCOME MEASURES: Self-reported
      anhedonia and depression (with anhedonia). RESULTS: In both samples, individuals
      who experienced childhood physical abuse were considerably more likely to report
      lifetime anhedonia. However, in those with 1 or more copies of the minor allele
      of rs1049353, this pathogenic effect of childhood physical abuse was attenuated.
      Thus, in participants reporting childhood physical abuse, although 57.1% of those
      homozygous for the major allele reported anhedonia, only 28.6% of those who were
      carriers of the minor allele reported it (P=.01). The rs1049353 polymorphism also
      buffered the effects of childhood physical abuse on major depressive disorder;
      however, this influence was largely attributable to anhedonic depression. These
      effects were also noted in an independent sample, in which minor allele carriers
      were at decreased risk for anhedonia even when exposed to physical abuse.
      CONCLUSIONS: Consistent with preclinical findings, a synonymous CNR1
      polymorphism, rs1049353, is linked to the effects of stress attributable to
      childhood physical abuse on anhedonia and anhedonic depression. This polymorphism
      reportedly resides in the neighborhood of an exon splice enhancer; hence, future
      studies should carefully examine its effect on expression and conformational
      variation in CNR1, particularly in relation to stress adaptation.

PMID- 22393206
TI  - Genetic and familial environmental influences on the risk for drug abuse: a
      national Swedish adoption study.
AB  - CONTEXT: Prior research suggests that drug abuse (DA) is strongly influenced by
      both genetic and familial environmental factors. No large-scale adoption study
      has previously attempted to verify and integrate these findings. OBJECTIVE: To
      determine how genetic and environmental factors contribute to the risk for DA.
      DESIGN: Follow-up in 9 public databases (1961-2009) of adopted children and their
      biological and adoptive relatives. SETTING: Sweden. PARTICIPANTS: The study
      included 18 115 adopted children born between 1950 and 1993; 78,079 biological
      parents and siblings; and 51,208 adoptive parents and siblings. MAIN OUTCOME
      MEASURES: Drug abuse recorded in medical, legal, or pharmacy registry records.
      RESULTS: Risk for DA was significantly elevated in the adopted offspring of
      biological parents with DA (odds ratio, 2.09; 95% CI, 1.66-2.62), in biological
      full and half siblings of adopted children with DA (odds ratio, 1.84; 95% CI,
      1.28-2.64; and odds ratio, 1.41; 95% CI, 1.19-1.67, respectively), and in
      adoptive siblings of adopted children with DA (odds ratio, 1.95; 95% CI, 1.43
      2.65). A genetic risk index (including biological parental or sibling history of
      DA, criminal activity, and psychiatric or alcohol problems) and an environmental
      risk index (including adoptive parental history of divorce, death, criminal
      activity, and alcohol problems, as well as an adoptive sibling history of DA and
      psychiatric or alcohol problems) both strongly predicted the risk for DA.
      Including both indices along with sex and age at adoption in a predictive model
      revealed a significant positive interaction between the genetic and environmental
      risk indices. CONCLUSIONS: Drug abuse is an etiologically complex syndrome
      strongly influenced by a diverse set of genetic risk factors reflecting a
      specific liability to DA, by a vulnerability to other externalizing disorders,
      and by a range of environmental factors reflecting marital instability, as well
      as psychopathology and criminal behavior in the adoptive home. Adverse
      environmental effects on DA are more pathogenic in individuals with high levels
      of genetic risk. These results should be interpreted in the context of
      limitations of the diagnosis of DA from registries.

PMID- 22393207
TI  - The Diesel Exhaust in Miners study: a cohort mortality study with emphasis on
      lung cancer.
AB  - BACKGROUND: Current information points to an association between diesel exhaust
      exposure and lung cancer and other mortality outcomes, but uncertainties remain.
      METHODS: We undertook a cohort mortality study of 12 315 workers exposed to
      diesel exhaust at eight US non-metal mining facilities. Historical measurements
      and surrogate exposure data, along with study industrial hygiene measurements,
      were used to derive retrospective quantitative estimates of respirable elemental
      carbon (REC) exposure for each worker. Standardized mortality ratios and
      internally adjusted Cox proportional hazard models were used to evaluate REC
      exposure-associated risk. Analyses were both unlagged and lagged to exclude
      recent exposure such as that occurring in the 15 years directly before the date
      of death. RESULTS: Standardized mortality ratios for lung cancer (1.26, 95%
      confidence interval [CI] = 1.09 to 1.44), esophageal cancer (1.83, 95% CI = 1.16
      to 2.75), and pneumoconiosis (12.20, 95% CI = 6.82 to 20.12) were elevated in the
      complete cohort compared with state-based mortality rates, but all-cause, bladder
      cancer, heart disease, and chronic obstructive pulmonary disease mortality were
      not. Differences in risk by worker location (ever-underground vs surface only)
      initially obscured a positive diesel exhaust exposure-response relationship with
      lung cancer in the complete cohort, although it became apparent after adjustment
      for worker location. The hazard ratios (HRs) for lung cancer mortality increased
      with increasing 15-year lagged cumulative REC exposure for ever-underground
      workers with 5 or more years of tenure to a maximum in the 640 to less than 1280
      MUg/m(3)-y category compared with the reference category (0 to <20 MUg/m(3)-y; 30
      deaths compared with eight deaths of the total of 93; HR = 5.01, 95% CI = 1.97 to
      12.76) but declined at higher exposures. Average REC intensity hazard ratios rose
      to a plateau around 32 MUg/m(3). Elevated hazard ratios and evidence of exposure
      response were also seen for surface workers. The association between diesel
      exhaust exposure and lung cancer risk remained after inclusion of other work
      related potentially confounding exposures in the models and were robust to
      alternative approaches to exposure derivation. CONCLUSIONS: The study findings
      provide further evidence that exposure to diesel exhaust increases risk of
      mortality from lung cancer and have important public health implications.

PMID- 22393208
TI  - The problem with Diesel.

PMID- 22393210
TI  - Expanding cancer prevention and treatment in the developing world.

PMID- 22393209
TI  - The Diesel Exhaust in Miners study: a nested case-control study of lung cancer
      and diesel exhaust.
AB  - BACKGROUND: Most studies of the association between diesel exhaust exposure and
      lung cancer suggest a modest, but consistent, increased risk. However, to our
      knowledge, no study to date has had quantitative data on historical diesel
      exposure coupled with adequate sample size to evaluate the exposure-response
      relationship between diesel exhaust and lung cancer. Our purpose was to evaluate
      the relationship between quantitative estimates of exposure to diesel exhaust and
      lung cancer mortality after adjustment for smoking and other potential
      confounders. METHODS: We conducted a nested case-control study in a cohort of 12
      315 workers in eight non-metal mining facilities, which included 198 lung cancer
      deaths and 562 incidence density-sampled control subjects. For each case subject,
      we selected up to four control subjects, individually matched on mining facility,
      sex, race/ethnicity, and birth year (within 5 years), from all workers who were
      alive before the day the case subject died. We estimated diesel exhaust exposure,
      represented by respirable elemental carbon (REC), by job and year, for each
      subject, based on an extensive retrospective exposure assessment at each mining
      facility. We conducted both categorical and continuous regression analyses
      adjusted for cigarette smoking and other potential confounding variables (eg,
      history of employment in high-risk occupations for lung cancer and a history of
      respiratory disease) to estimate odds ratios (ORs) and 95% confidence intervals
      (CIs). Analyses were both unlagged and lagged to exclude recent exposure such as
      that occurring in the 15 years directly before the date of death (case
      subjects)/reference date (control subjects). All statistical tests were two
      sided. RESULTS: We observed statistically significant increasing trends in lung
      cancer risk with increasing cumulative REC and average REC intensity. Cumulative
      REC, lagged 15 years, yielded a statistically significant positive gradient in
      lung cancer risk overall (P (trend) = .001); among heavily exposed workers (ie,
      above the median of the top quartile [REC >= 1005 MUg/m(3)-y]), risk was
      approximately three times greater (OR = 3.20, 95% CI = 1.33 to 7.69) than that
      among workers in the lowest quartile of exposure. Among never smokers, odd ratios
      were 1.0, 1.47 (95% CI = 0.29 to 7.50), and 7.30 (95% CI = 1.46 to 36.57) for
      workers with 15-year lagged cumulative REC tertiles of less than 8, 8 to less
      than 304, and 304 MUg/m(3)-y or more, respectively. We also observed an
      interaction between smoking and 15-year lagged cumulative REC (P (interaction) =
      .086) such that the effect of each of these exposures was attenuated in the
      presence of high levels of the other. CONCLUSION: Our findings provide further
      evidence that diesel exhaust exposure may cause lung cancer in humans and may
      represent a potential public health burden.

PMID- 22393211
TI  - Gene linked to pancreatic cancer.

PMID- 22393212
TI  - Breast cancer in men.

PMID- 22393214
TI  - Art and images in psychiatry. Come Unto These Yellow Sands.

PMID- 22393215
TI  - Predicting psychosis: meta-analysis of transition outcomes in individuals at high
      clinical risk.
AB  - CONTEXT: A substantial proportion of people at clinical high risk of psychosis
      will develop a psychotic disorder over time. However, the risk of transition to
      psychosis varies between centers, and some recent work suggests that the risk of
      transition may be declining. OBJECTIVE: To quantitatively examine the literature
      to date reporting the transition risk to psychosis in subjects at clinical high
      risk. DATA SOURCES: The electronic databases were searched until January 2011.
      All studies reporting transition risks in patients at clinical high risk were
      retrieved. STUDY SELECTION: Twenty-seven studies met the inclusion criteria,
      comprising a total of 2502 patients. DATA EXTRACTION: Transition risks, as well
      as demographic, clinical, and methodologic variables, were extracted from each
      publication or obtained directly from its authors. DATA SYNTHESIS: There was a
      consistent transition risk, independent of the psychometric instruments used, of
      18% after 6 months of follow-up, 22% after 1 year, 29% after 2 years, and 36%
      after 3 years. Significant moderators accounting for heterogeneity across studies
      and influencing the transition risks were the age of participants, publication
      year, treatments received, and diagnostic criteria used. There was no publication
      bias, and a sensitivity analysis confirmed the robustness of the core findings.
      CONCLUSIONS: The state of clinical high risk is associated with a very high risk
      of developing psychosis within the first 3 years of clinical presentation, and
      the risk progressively increases across this period. The transition risk varies
      with the age of the patient, the nature of the treatment provided, and the way
      the syndrome and transition to psychosis are defined.

PMID- 22393216
TI  - Disordered corticolimbic interactions during affective processing in children and
      adolescents at risk for schizophrenia revealed by functional magnetic resonance
      imaging and dynamic causal modeling.
AB  - CONTEXT: Disordered functional architecture of brain networks may contribute to
      the well-documented increased risk for psychiatric disorders in offspring of
      patients with schizophrenia. OBJECTIVE: To investigate aberrant interactions
      between regions associated with affective processing in children and adolescent
      offspring of patients with schizophrenia (HR-SCZ group) and healthy control
      subjects using dynamic causal modeling of functional magnetic resonance imaging
      data. DESIGN: Subjects participated in a continuous affective processing task
      during which positive, negative, and neutral valenced faces were presented.
      Interactions between regions in the brain's face- and emotion-processing network
      were modeled using dynamic causal modeling. Multiple competing models were
      evaluated by a combinatorial approach and distinguished at the second level using
      Bayesian model selection before parameter inference. SETTING: Participants were
      recruited from the community. PARTICIPANTS: Twenty-four controls with no family
      history of psychosis (to the second degree) and 19 children and adolescent
      offspring of a parent with schizophrenia (age range, 8 to 20 years). RESULTS:
      Bayesian model selection revealed a winning model, the architecture of which
      revealed bidirectional frontolimbic connections that were modulated by valence.
      Analyses of parameter estimates revealed that HR-SCZ group members were
      characterized by (1) decreased driving inputs to the visual cortex; (2) decreased
      intrinsic coupling, most robustly between frontolimbic regions; and (3) increased
      modulatory inhibition by negative valence of frontolimbic connections (all P <
      .01, Bonferroni corrected). CONCLUSIONS: These results are the first
      demonstration of network analyses techniques for functional magnetic resonance
      imaging data in children and adolescents at risk for schizophrenia. Dysfunctional
      interactions within the emotional processing network provide evidence of latent
      vulnerabilities that may confer risk for disordered adolescent development and
      eventually the emergence of the manifest disorder.

PMID- 22393217
TI  - A dynamic view of depressive symptoms and neurocognitive change among patients
      with coronary artery disease.
AB  - CONTEXT: Older patients with coronary artery disease often experience depressive
      symptoms and are vulnerable to developing cognitive impairment. Whether
      depressive symptoms increase their risk of cognitive decline is unknown.
      OBJECTIVES: To examine the association between the stability of depressive
      symptoms and cognitive decline for 30 months among patients undergoing coronary
      angiography and to explore whether any observed associations were modified by the
      presence of the apolipoprotein E (APOE) epsilon4 allele. DESIGN: Cohort study.
      SETTING: Urban tertiary care hospital serving southern Alberta. PARTICIPANTS:
      Three hundred fifty patients 60 years or older (73.7% male) undergoing
      nonemergent catheterization (October 27, 2003, through February 28, 2007) without
      prior revascularization. We compared a baseline measure of depressive symptoms
      (Geriatric Depression Scale score >=5) with a dynamic measure capturing change
      from baseline to 12 months. MAIN OUTCOME MEASURES: Mean change in domain (z
      scores for attention/executive function, learning/memory, and verbal fluency) and
      global (raw Mini-Mental State Examination) cognitive scores from baseline to 6,
      12, and 30 months and from 12 to 30 months. RESULTS: In adjusted models,
      participants with persistent depressive symptoms (at baseline and >=1follow-up
      visit) showed significantly greater declines at 30 months in attention/executive
      function (mean z score change, -0.22), learning/memory (-0.19), verbal fluency (
      0.18), and global cognition (mean Mini-Mental State Examination [MMSE] score
      change, -0.99) compared with participants with no or baseline-only depressive
      symptoms. Persistent depressive symptoms were associated with significantly
      greater declines in all cognitive measures from 12 to 30 months after adjusting
      for sociodemographic and clinical factors. For global cognition, a significantly
      greater decline was evident for patients with persistent depressive symptoms and
      the APOE epsilon4 allele (mean MMSE score change, -2.93 [95% CI, -4.40 to 
      1.45]). CONCLUSIONS: Depressive symptoms persist in some patients with coronary
      artery disease, placing them at a greater risk for cognitive decline. Whether
      this decline is additionally modified by the presence of APOE epsilon4 requires
      further investigation.

PMID- 22393218
TI  - Suicide risk in primary care patients with major physical diseases: a case
      control study.
AB  - CONTEXT: Most previous studies have examined suicide risk in relation to a single
      physical disease. OBJECTIVES: To estimate relative risk across a range of
      physical diseases, to assess the confounding effect of clinical depression and
      effect modification by sex and age, and to examine physical illness
      multimorbidity. DESIGN: Nested case-control study. SETTING: Family practices in
      England (n = 224) [corrected] registered with the General Practice Research
      Database from January 1, 2001, through December 31, 2008. The case-control data
      were drawn from approximately 4.7 [corrected] million complete patient records,
      with complete linkage to national mortality records. PARTICIPANTS: A total of 873
      adult suicide cases and 17 460 living controls matched on age and sex were
      studied. The reference group for relative risk estimation consisted of people
      without any of the specific physical illnesses examined. MAIN OUTCOME MEASURES:
      Suicide and open verdicts. RESULTS: Among all patients, coronary heart disease,
      stroke, chronic obstructive pulmonary disease, and osteoporosis were linked with
      elevated suicide risk, and, with the exception of osteoporosis, the increase was
      explained by clinical depression. The only significantly elevated risk in men was
      with osteoporosis. Female effect sizes were greater, with 2- or 3-fold higher
      risk found among women diagnosed as having cancer, coronary heart disease,
      stroke, chronic obstructive pulmonary disease, and osteoporosis. In women with
      cancer and coronary heart disease, a significant elevation persisted after
      adjustment for depression. Overall, heightened risk was confined to physically
      ill women younger than 50 years and to older women with multiple physical
      diseases. CONCLUSIONS: Our findings indicate that clinical depression is a strong
      confounder of increased suicide risk among physically ill people. They also
      demonstrate an independent elevation in risk linked with certain diagnoses,
      particularly among women. Health care professionals working across all medical
      specialties should be vigilant for signs of undetected psychological symptoms.

PMID- 22393219
TI  - The ability of multifamily groups to improve treatment adherence in Mexican
      Americans with schizophrenia.
AB  - CONTEXT: Evidence-based interventions to improve medication adherence among
      patients with schizophrenia are lacking. Although family psychoeducation has
      demonstrated efficacy in improving outcomes in schizophrenia, empirical support
      for its ability to enhance medication adherence is scarce. OBJECTIVE: To
      determine whether a culturally adapted, multifamily group (MFG) therapy would
      increase medication adherence and decrease psychiatric hospitalizations for
      Spanish-speaking Mexican Americans with schizophrenia. DESIGN: A total of 174
      Mexican American adults with schizophrenia-spectrum disorder and their key
      relatives were studied in a 3-armed, randomized controlled trial of MFG therapy
      focused on improving medication adherence. Assessments occurred at baseline and
      at 4, 8, 12, 18, and 24 months. SETTING: Two community mental health centers in
      Los Angeles, California. PARTICIPANTS: Patients had a diagnosis of schizophrenia
      or schizoaffective disorder with a recent exacerbation of psychotic symptoms and
      nonadherence to medication before enrollment. Intervention  Patients participated
      in 1 of 2 MFGs (MFG-adherence or MFG-standard) or treatment as usual. Groups
      convened twice monthly in 90-minute sessions for 1 year. MAIN OUTCOME MEASURES:
      The Treatment Compliance Interview uses multiple sources of information to
      quantify medication adherence. Computerized records were used to collect
      information on the use of inpatient resources. RESULTS: At the end of the 1-year
      treatment, MFG-adherence was associated with higher medication adherence than MFG
      standard or treatment as usual only (F = 6.41; P = .003). The MFG-adherence
      participants had a longer time to first hospitalization (chi(2) = 13.3; P = .001)
      and were less likely to be hospitalized than those in MFG-standard (chi(2) = 8.2;
      P = .04) and treatment as usual alone (chi(2) = 11.3; P < .001). Increased
      adherence accounted for one-third of the overall effect of treatment on the
      reduced risk for psychiatric hospitalization. CONCLUSION: Multifamily group
      therapy specifically tailored to improve medication adherence through a focus on
      the beliefs and attitudes of the target population is associated with improved
      outcome for Mexican American adults with schizophrenia-spectrum disorders. Trial
      Registration  clinicaltrials.gov Identifier: NCT01125267.

PMID- 22393220
TI  - Increased frontotemporal activation during pain observation in sexual sadism:
      preliminary findings.
AB  - CONTEXT: Sexual sadism is a psychiatric disorder in which sexual pleasure is
      derived from inflicting pain, suffering, or humiliation on others. While the
      psychological and forensic aspects of sexual sadism have been well characterized,
      little is known about the neurocognitive circuitry associated with the disorder.
      Sexual sadists show increased peripheral sexual arousal when observing other
      individuals in pain. The neural mechanisms underlying this unusual response are
      not well understood. We predicted that sadists relative to nonsadists would show
      increased responses in brain regions associated with sexual arousal (amygdala,
      hypothalamus, and ventral striatum) and affective pain processing (anterior
      cingulate and anterior insula) during pain observation. OBJECTIVE: To study the
      neural correlates of pain observation in sadists and nonsadists. DESIGN: Case
      control cross-sectional study. Sadists and nonsadists viewed 50 social scenes, 25
      that depicted a person in pain (eg, one person stabbing another person's hand
      with scissors) and 25 thematically matched no-pain pictures (eg, one person
      stabbing a table with scissors, with another person's hand nearby). Pain severity
      ratings (range, 0 [none] to 4 [severe]) were acquired following each picture
      presentation. SETTING: Sand Ridge Secure Treatment Center, Mauston, Wisconsin.
      PARTICIPANTS: Fifteen violent sexual offenders, including 8 sadists and 7
      nonsadists (defined using the Severe Sexual Sadism Scale) who were matched for
      age, IQ, and education. MAIN OUTCOME MEASURES: Hemodynamic response revealed by
      functional magnetic resonance imaging and pain severity ratings. RESULTS: Sadists
      relative to nonsadists showed greater amygdala activation when viewing pain
      pictures. They also rated pain pictures higher on pain severity than nonsadists.
      Sadists but not nonsadists showed a positive correlation between pain severity
      ratings and activity in the anterior insula. CONCLUSION: These results provide
      neurobehavioral evidence of unusually heightened sensitivity to the pain of
      others in sadists.

PMID- 22393222
TI  - Criteria for premenstrual dysphoric disorder: secondary analyses of relevant data
      sets.
AB  - CONTEXT: There is substantial information that premenstrual dysphoric disorder
      (PMDD) is a clinically significant disorder with biological underpinnings that
      differ from other psychiatric disorders. However, data regarding the symptoms
      noted in DSM-IV and timing of their expression in the menstrual cycle have had
      little empirical support. OBJECTIVE: To provide evidence informing the
      definitional criteria for PMDD. DESIGN: Prospective surveys. SETTING: General
      community and clinical settings. PARTICIPANTS: Two cohorts that included a
      representative sample and a self-identified treatment-seeking cohort. Main
      Outcome Measure  Daily ratings of perimenstrual symptoms and functioning.
      RESULTS: Mood and physical symptoms were most severe and were accompanied by
      impairment in the 4 days before through the first 2 days of menses for the self
      identified group and in the 3 days before through the first 3 days of menses in
      the community sample. The most problematic symptoms endorsed were those listed in
      DSM-IV, but depressed mood was less frequent than other affective symptoms. In
      the combined sample, 4 or more symptoms was the optimal cutoff point for
      maximizing both sensitivity and specificity when predicting impairment.
      CONCLUSIONS: This is informative for DSM-5 in that the most symptomatic period
      typically includes the few days before through the first 3 days of menses rather
      than only the premenstrual phase. Further, we validated the salience of PMDD
      symptoms included in DSM-IV. Although the number of symptoms most associated with
      distress and impairment differed between the 2 cohorts, results from the combined
      cohort suggest that 4 symptoms are linked with impairment from PMDD symptoms.

PMID- 22393223
TI  - Minimizing and communicating radiation risk in pediatric nuclear medicine.
AB  - The value of pediatric nuclear medicine is well established. Pediatric patients
      are referred to nuclear medicine from nearly all pediatric specialties including
      urology, oncology, cardiology, gastroenterology, and orthopedics. Radiation
      exposure is associated with a potential, small, risk of inducing cancer in the
      patient later in life and is higher in younger patients. Recently, there has been
      enhanced interest in exposure to radiation from medical imaging. Thus, it is
      incumbent on practitioners of pediatric nuclear medicine to have an understanding
      of dosimetry and radiation risk to communicate effectively with their patients
      and their families. This article reviews radiation dosimetry for
      radiopharmaceuticals and also CT given the recent proliferation of PET/CT and
      SPECT/CT. It also describes the scientific basis for radiation risk estimation in
      the context of pediatric nuclear medicine. Approaches for effective communication
      of risk to patients' families are discussed. Lastly, radiation dose reduction in
      pediatric nuclear medicine is explicated.

PMID- 22393221
TI  - Common heritable contributions to low-risk trauma, high-risk trauma,
      posttraumatic stress disorder, and major depression.
AB  - CONTEXT: Understanding the relative contributions of genetic and environmental
      factors to trauma exposure, posttraumatic stress disorder (PTSD), and major
      depressive disorder (MDD) is critical to developing etiologic models of these
      conditions and their co-occurrence. OBJECTIVES: To quantify heritable influences
      on low-risk trauma, high-risk trauma, PTSD, and MDD and to estimate the degree of
      overlap between genetic and environmental sources of variance in these 4
      phenotypes. DESIGN: Adult twins and their siblings were ascertained from a large
      population-based sample of female and male twin pairs on the basis of screening
      items for childhood sexual abuse and physical abuse obtained in a previous
      assessment of this cohort. SETTING: Structured psychiatric telephone interviews.
      PARTICIPANTS: Total sample size of 2591: 996 female and 536 male twins; 625
      female and 434 male nontwin siblings. MAIN OUTCOME MEASURE: Lifetime low- and
      high-risk trauma exposure, PTSD, and MDD. RESULTS: In the best-fitting genetic
      model, 47% of the variance in low-risk trauma exposure and 60% of the variance in
      high-risk trauma exposure was attributable to additive genetic factors. Heritable
      influences accounted for 46% of the variance in PTSD and 27% of the variance in
      MDD. An extremely high degree of genetic overlap was observed between high-risk
      trauma exposure and both PTSD (r = 0.89; 95% CI, 0.78-0.99) and MDD (r = 0.89;
      95% CI, 0.77-0.98). Complete correlation of genetic factors contributing to PTSD
      and to MDD (r = 1.00) was observed. CONCLUSIONS: The evidence suggests that
      almost all the heritable influences on high-risk trauma exposure, PTSD, and MDD,
      can be traced to the same sources; that is, genetic risk is not disorder
      specific. Individuals with a positive family history of either PTSD or MDD are at
      elevated risk for both disorders and should be closely monitored after a
      traumatic experience for symptoms of PTSD and MDD.

PMID- 22393224
TI  - Evaluation of left and right ventricular ejection fraction and volumes from gated
      blood-pool SPECT in patients with dilated cardiomyopathy: comparison with cardiac
      MRI.
AB  - This prospective study evaluated the accuracy of electrocardiogram-gated blood
      pool SPECT (GBPS) for the assessment of left ventricular (LV) and right
      ventricular (RV) ejection fraction (EF), end-diastolic volume (EDV), and end
      systolic volume (ESV) in patients with dilated cardiomyopathy (DCM), using
      cardiac magnetic resonance (CMR) imaging as the reference standard. METHODS:
      Thirty-two patients (24 men and 8 women; mean age, 51 y) with a diagnosis of
      idiopathic DCM underwent GBPS and CMR. LV and RV parameters including EDV, ESV,
      and EF from GBPS were calculated using fully automated gradient software and
      compared with those obtained by CMR. RESULTS: Biventricular volumes were
      underestimated by GBPS, compared with CMR (P < 0.001). We found no statistical
      difference between these 2 methods in the assessment of LV EF (P = 0.23), whereas
      RV EF was overestimated by GBPS (P < 0.001 vs. CMR). Regression analysis yielded
      significant correlations between GBPS and CMR in the assessments of biventricular
      parameters (r = 0.83 for LV EDV, 0.88 for LV ESV, 0.89 for LV EF, 0.86 for RV
      EDV, 0.86 for RV ESV, and 0.62 for RV EF; all P < 0.001). Comparison of the
      deviations of RV indices between GBPS and CMR with the ratio of RV EDV to LV EDV
      showed that there was a statistically significant trend for RV volumes to be
      underestimated and for RV EF to be overestimated as the biventricular volumetric
      ratio decreased (r = 0.61 for RV EDV, 0.68 for RV ESV, and -0.55 for RV EF; all P
      < 0.001). CONCLUSION: For patients with DCM, GBPS correlated well with CMR for
      the assessment of biventricular parameters, but RV indices should be cautiously
      interpreted.

PMID- 22393225
TI  - Ultrasound microbubbles for molecular diagnosis, therapy, and theranostics.
AB  - Ultrasound imaging is clinically established for routine screening examinations
      of breast, abdomen, neck, and other soft tissues, as well as for therapy
      monitoring. Microbubbles as vascular contrast agents improve the detection and
      characterization of cancerous lesions, inflammatory processes, and cardiovascular
      pathologies. Taking advantage of the excellent sensitivity and specificity of
      ultrasound for microbubble detection, molecular imaging can be realized by
      binding antibodies, peptides, and other targeting moieties to microbubble
      surfaces. Molecular microbubbles directed against various targets such as
      vascular endothelial growth factor receptor-2, vascular cell adhesion molecule 1,
      intercellular adhesion molecule 1, selectins, and integrins were developed and
      were shown in preclinical studies to be able to selectively bind to tumor blood
      vessels and atherosclerotic plaques. Currently, the first microbubble
      formulations targeted to angiogenic vessels in prostate cancers are being
      evaluated clinically. However, microbubbles can be used for more than diagnosis:
      disintegrating microbubbles emit acoustic forces that are strong enough to induce
      thrombolysis, and they can also be used for facilitating drug and gene delivery
      across biologic barriers. This review on the use of microbubbles for ultrasound
      based molecular imaging, therapy, and theranostics addresses innovative concepts
      and identifies areas in which clinical translation is foreseeable in the near
      future.

PMID- 22393226
TI  - Hippocrates and certification.

PMID- 22393227
TI  - SNM 2012 annual meeting in Miami.

PMID- 22393228
TI  - BMD rescreening and procedure overuse.

PMID- 22393229
TI  - Howard J. Dworkin, MD, 1932-2012.

PMID- 22393230
TI  - Update on CardioGen-82.

PMID- 22393231
TI  - SNM and AACR announce joint conference.

PMID- 22393232
TI  - SNM and global cooperation.

PMID- 22393233
TI  - GRIM-19-mediated translocation of STAT3 to mitochondria is necessary for TNF
      induced necroptosis.
AB  - Tumor necrosis factor (TNF) can induce necroptosis, wherein inhibition of caspase
      activity prevents apoptosis but initiates an alternative programmed necrosis. The
      activity of receptor-interacting serine/threonine-protein kinase 1 (RIPK-1) is
      required for necroptosis to proceed, with suppression of RIPK-1 expression or
      inhibition of RIPK-1 activity with necrostatin-1 preventing TNF-induced
      necroptosis. Downstream from the TNF receptor, the generation of reactive oxygen
      species at the mitochondria has been identified as necessary for the execution of
      necroptosis; with antioxidants and inhibitors of mitochondrial complex I
      preventing TNF-induced cytotoxicity. However, components of the signaling pathway
      that lie between activated RIPK-1 and the mitochondria are unknown. In the study
      reported here we demonstrate that during TNF-induced necroptosis, STAT3 is
      phosphorylated on serine 727, which is dependent on RIPK-1 expression or
      activity. The phosphorylation of STAT3 induces interaction with GRIM-19, a
      subunit of mitochondrial complex I, with a resultant translocation of STAT3 to
      the mitochondria, where it induces an increase in reactive oxygen species
      production and cell death.

PMID- 22393234
TI  - Spatiotemporal resolution of mast cell granule exocytosis reveals correlation
      with Ca2+ wave initiation.
AB  - Mast cell activation initiated by antigen-mediated crosslinking of IgE receptors
      results in stimulated exocytosis of secretory lysosomes in the process known as
      degranulation. Much has been learned about the molecular mechanisms important for
      this process, including the crucial role of Ca(2+) mobilization, but spatio
      temporal relationships between stimulated Ca(2+) mobilization and granule
      exocytosis are incompletely understood. Here we use a novel imaging-based method
      that uses fluorescein isothiocyanate (FITC)-dextran as a reporter for granule
      exocytosis in RBL mast cells and takes advantage of the pH sensitivity of FITC.
      We demonstrate the selectivity of FITC-dextran, accumulated by fluid-phase
      uptake, as a marker for secretory lysosomes, and we characterize its capacity to
      delineate different exocytotic events, including full fusion, kiss-and-run
      transient fusion and compound exocytosis. Using this method, we find strong
      dependence of degranulation kinetics on the duration of cell to substrate
      attachment. We combine imaging of degranulation and Ca(2+) dynamics to
      demonstrate a spatial relationship between the sites of Ca(2+) wave initiation in
      extended cell protrusions and exocytosis under conditions of limited antigen
      stimulation. In addition, we find that the spatially proximal Ca(2+) signaling
      and secretory events correlate with participation of TRPC1 channels in Ca(2+)
      mobilization.

PMID- 22393237
TI  - Microprocessor dynamics and interactions at endogenous imprinted C19MC microRNA
      genes.
AB  - Nuclear primary microRNA (pri-miRNA) processing catalyzed by the DGCR8-Drosha
      (Microprocessor) complex is highly regulated. Little is known, however, about how
      microRNA biogenesis is spatially organized within the mammalian nucleus. Here, we
      image for the first time, in living cells and at the level of a single microRNA
      cluster, the intranuclear distribution of untagged, endogenously-expressed pri
      miRNAs generated at the human imprinted chromosome 19 microRNA cluster (C19MC),
      from the environment of transcription sites to single molecules of fully released
      DGCR8-bound pri-miRNAs dispersed throughout the nucleoplasm. We report that a
      large fraction of Microprocessor concentrates onto unspliced C19MC pri-miRNA
      deposited in close proximity to their genes. Our live-cell imaging studies
      provide direct visual evidence that DGCR8 and Drosha are targeted post
      transcriptionally to C19MC pri-miRNAs as a preformed complex but dissociate
      separately. These dynamics support the view that, upon pri-miRNA loading and most
      probably concomitantly with Drosha-mediated cleavages, Microprocessor undergoes
      conformational changes that trigger the release of Drosha while DGCR8 remains
      stably bound to pri-miRNA.

PMID- 22393235
TI  - A RUNX2-HDAC1 co-repressor complex regulates rRNA gene expression by modulating
      UBF acetylation.
AB  - The osteogenic and oncogenic transcription factor RUNX2 downregulates the RNA
      polymerase I (RNA Pol I)-mediated transcription of rRNAs and changes histone
      modifications associated with the rDNA repeat. However, the mechanisms by which
      RUNX2 suppresses rRNA transcription are not well understood. RUNX2 cofactors such
      as histone deacetylases (HDACs) play a key role in chromatin remodeling and
      regulation of gene transcription. Here, we show that RUNX2 recruits HDAC1 to the
      rDNA repeats in osseous cells. This recruitment alters the histone modifications
      associated with active rRNA-encoding genes and causes deacetylation of the
      protein upstream binding factor (UBF, also known as UBTF). Downregulation of
      RUNX2 expression reduces the localization of HDAC1 to the nucleolar periphery and
      also decreases the association between HDAC1 and UBF. Functionally, depletion of
      HDAC1 relieves the RUNX2-mediated repression of rRNA-encoding genes and
      concomitantly increases cell proliferation and global protein synthesis in
      osseous cells. Our findings collectively identify a RUNX2-HDAC1-dependent
      mechanism for the regulation of rRNA-encoding genes and suggest that there is
      plasticity to RUNX2-mediated epigenetic control, which is mediated through
      selective mitotic exclusion of co-regulatory factors.

PMID- 22393238
TI  - Focal adhesion kinase modulates Cdc42 activity downstream of positive and
      negative axon guidance cues.
AB  - There is biochemical, imaging and functional evidence that Rho GTPase signaling
      is a crucial regulator of actin-based structures such as lamellipodia and
      filopodia. However, although Rho GTPases are believed to serve similar functions
      in growth cones, the spatiotemporal dynamics of Rho GTPase signaling has not been
      examined in living growth cones in response to known axon guidance cues. Here we
      provide the first measurements of Cdc42 activity in living growth cones acutely
      stimulated with both growth-promoting and growth-inhibiting axon-guidance cues.
      Interestingly, we find that both permissive and repulsive factors can work by
      modulating Cdc42 activity, but in opposite directions. We find that the growth
      promoting factors laminin and BDNF activate Cdc42, whereas the inhibitor Slit2
      reduces Cdc42 activity in growth cones. Remarkably, we find that regulation of
      focal adhesion kinase (FAK) activity is a common upstream modulator of Cdc42 by
      BDNF, laminin and Slit. These findings suggest that rapid modulation of Cdc42
      signaling through FAK by receptor activation underlies changes in growth cone
      motility in response to permissive and repulsive guidance cues.

PMID- 22393239
TI  - Single-molecule tools elucidate H2A.Z nucleosome composition.
AB  - Although distinct epigenetic marks correlate with different chromatin states, how
      they are integrated within single nucleosomes to generate combinatorial signals
      remains largely unknown. We report the successful implementation of single
      molecule tools constituting fluorescence correlation spectroscopy (FCS), pulse
      interleave excitation-based Forster resonance energy transfer (PIE-FRET) and
      fluorescence lifetime imaging-based FRET (FLIM-FRET) to elucidate the composition
      of single nucleosomes containing histone variant H2A.Z (Htz1p in yeast) in vitro
      and in vivo. We demonstrate that yeast nucleosomes containing Htz1p are primarily
      composed of H4 K12ac and H3 K4me3 but not H3 K36me3 and that these patterns are
      conserved in mammalian cells. Quantification of epigenetic modifications in
      nucleosomes will provide a new dimension to epigenetics research and lead to a
      better understanding of how these patterns contribute to the targeting of
      chromatin-binding proteins and chromatin structure during gene regulation.

PMID- 22393240
TI  - Intra-hematopoietic cell fusion as a source of somatic variation in the
      hematopoietic system.
AB  - Cell fusion plays a well-recognized, physiological role during development. Bone
      marrow-derived hematopoietic cells have been shown to fuse with non-hematopoietic
      cells in a wide variety of tissues. Some organs appear to resolve the changes in
      ploidy status, generating functional and mitotically-competent events. However,
      cell fusion exclusively involving hematopoietic cells has not been reported.
      Indeed, genomic copy number variation in highly replicative hematopoietic cells
      is widely considered a hallmark of malignant transformation. Here we show that
      cell fusion occurs between cells of the hematopoietic system under injury as well
      as non-injury conditions. Experiments reveal the acquisition of genetic markers
      in fusion products, their tractable maintenance during hematopoietic
      differentiation and long-term persistence after serial transplantation. Fusion
      events were identified in clonogenic progenitors as well as differentiated
      myeloid and lymphoid cells. These observations provide a new experimental model
      for the study of non-pathogenic somatic diversity in the hematopoietic system.

PMID- 22393241
TI  - miR-221 and miR-222 promote Schwann cell proliferation and migration by targeting
      LASS2 after sciatic nerve injury.
AB  - microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the
      post-transcriptional level. Their roles in regulating the responses of Schwann
      cells (SCs) to injury stimuli remain unexplored. Here we report dynamic
      alteration of miRNA expression following rat sciatic nerve injury using
      microarray analysis. We harvested the proximal nerve stumps and identified 77
      miRNAs that showed significant changes at four time points after nerve
      transection. Subsequently, we analyzed the expression pattern of miRNA, selected
      one significant profile, and then integrated putative miRNA targets with
      differentially expressed mRNA yielding 274 potential targets. The 274 targets
      were mainly involved in cell proliferation, cell locomotion and cellular
      homeostasis that were known to play important roles in modulating cell phenotype.
      The upregulation of the miR-221 and miR-222 cluster (miR-221/222) was found to
      correlate with the injury-induced SC phenotypic modulation. Enhanced expression
      of miR-221/222 could promote SC proliferation and migration in vitro, whereas
      silencing their expression resulted in a reduced proliferation and migration.
      Further studies revealed that longevity assurance homologue 2 (LASS2) was a
      direct target of miR-221/222 in SCs because miR-221/222 bound directly to the 3'
      untranslated region of LASS2, thus reducing both mRNA and protein levels of
      LASS2. Silencing of LASS2 recapitulated the effects of miR-221/222 mimics,
      whereas enforced knockdown of LASS2 reversed the suppressive effects of miR
      221/222 inhibitors. Our findings indicate that injury promotes SC proliferation
      and migration through the regulation of miR-221/222 by targeting LASS2, and
      provide new insights into the role of miRNAs in nerve regeneration.

PMID- 22393242
TI  - ZIP4 in homologous chromosome synapsis and crossover formation in rice meiosis.
AB  - In budding yeast, the ZMM complex is closely associated with class I crossovers
      and synaptonemal complex (SC) formation. However, the relationship between the
      ZMM genes remains unclear in most higher eukaryotes. Here, we identify the rice
      ZIP4 homolog, a member of the ZMM gene group, and explore its relationship with
      two other characterized ZMM genes, MER3 and ZEP1. Our results show that in the
      rice zip4 mutant, the chiasma frequency is greatly reduced, although synapsis
      proceeds with only mild defects. Immunocytological analyses of wild-type rice
      reveal that ZIP4 presents as punctuate foci and colocalizes with MER3 in prophase
      I meiocytes. Additionally, ZIP4 is essential for the loading of MER3 onto
      chromosomes, but not vice versa. Double-mutant analyses show that zip4 mer3
      displays a greater decrease in the mean number of chiasmata than either of the
      zip4 or mer3 single mutants, suggesting that ZIP4 and MER3 work cooperatively to
      promote CO formation but their individual contributions are not completely
      identical in rice. Although zep1 alone gives an increased chiasma number, both
      zip4 zep1 and mer3 zep1 show a much lower chiasma number than the zip4 or mer3
      single mutants. These results imply that the normal functions of ZIP4 and MER3
      are required for the regulation of COs by ZEP1.

PMID- 22393243
TI  - Ciliogenesis in Caenorhabditis elegans requires genetic interactions between
      ciliary middle segment localized NPHP-2 (inversin) and transition zone-associated
      proteins.
AB  - The cystic kidney diseases nephronophthisis (NPHP), Meckel-Gruber syndrome (MKS)
      and Joubert syndrome (JBTS) share an underlying etiology of dysfunctional cilia.
      Patients diagnosed with NPHP type II have mutations in the gene INVS (also known
      as NPHP2), which encodes inversin, a cilia localizing protein. Here, we show that
      the C. elegans inversin ortholog, NPHP-2, localizes to the middle segment of
      sensory cilia and that nphp-2 is partially redundant with nphp-1 and nphp-4
      (orthologs of human NPHP1 and NPHP4, respectively) for cilia placement within the
      head and tail sensilla. nphp-2 also genetically interacts with MKS ciliopathy
      gene orthologs, including mks-1, mks-3, mks-6, mksr-1 and mksr-2, in a sensilla
      dependent manner to control cilia formation and placement. However, nphp-2 is not
      required for correct localization of the NPHP- and MKS-encoded ciliary transition
      zone proteins or for intraflagellar transport (IFT). We conclude that INVS/NPHP2
      is conserved in C. elegans and that nphp-2 plays an important role in C. elegans
      cilia by acting as a modifier of the NPHP and MKS pathways to control cilia
      formation and development.

PMID- 22393244
TI  - Changes in intranuclear mobility of mature snRNPs provide a mechanism for
      splicing defects in spinal muscular atrophy.
AB  - It is becoming increasingly clear that defects in RNA metabolism can lead to
      disease. Spinal muscular atrophy (SMA), a leading genetic cause of infant
      mortality, results from insufficient amounts of survival motor neuron (SMN)
      protein. SMN is required for the biogenesis of small nuclear ribonucleoproteins
      (snRNPs): essential components of the spliceosome. Splicing abnormalities have
      been detected in models of SMA but it is unclear how lowered SMN affects the
      fidelity of pre-mRNA splicing. We have examined the dynamics of mature snRNPs in
      cells depleted of SMN and demonstrated that SMN depletion increases the mobility
      of mature snRNPs within the nucleus. To dissect the molecular mechanism by which
      SMN deficiency affects intranuclear snRNP mobility, we employed a panel of
      inhibitors of different stages of pre-mRNA processing. This in vivo modelling
      demonstrates that snRNP mobility is altered directly as a result of impaired
      snRNP maturation. Current models of nuclear dynamics predict that subnuclear
      structures, including the spliceosome, form by self-organization mediated by
      stochastic interactions between their molecular components. Thus, alteration of
      the intranuclear mobility of snRNPs provides a molecular mechanism for splicing
      defects in SMA.

PMID- 22393245
TI  - Suppressor role of androgen receptor in proliferation of prostate basal
      epithelial and progenitor cells.
AB  - Early studies have reported the differential roles of androgen receptor (AR) in
      different types (luminal, basal intermediate, and stromal) of prostate cancer
      cells. In vivo mouse model tumor studies using the total prostate epithelial
      knockout mice (pes-ARKO) also revealed that AR played a suppressive role in
      proliferation of the CK5(+)/CK8(+) progenitor/intermediate cells but a positive
      role in the CK5(-)/CK8(+) luminal epithelial cells. Using three different
      resources (one human basal epithelial cell line, one mouse basal epithelial
      originated progenitor cell line, and a basal epithelium-specific ARKO mouse
      model), we here demonstrated that the AR in basal epithelial cells of normal
      prostate plays a suppressive role in their proliferation but a positive role in
      differentiation into luminal epithelial cells. These results led us to conclude
      that ARs may play a negative role to suppress CK5(+) basal epithelial and
      progenitor cell proliferation, yet play an essential role to drive basal
      epithelial cells into more differentiated states. These results may explain why
      differential AR expression in different cell types within normal prostate is
      needed and suggest that ARs in prostate basal epithelial cells, although
      expressed at a very low level, are necessary to maintain the balance between
      progenitor cells and differentiated luminal epithelial cells.

PMID- 22393247
TI  - Diltiazem enhances the apoptotic effects of proteasome inhibitors to induce
      prostate cancer cell death.
AB  - Diltiazem is a calcium channel blocker used to treat cardiovascular ailments. In
      addition, reports suggest that diltiazem induces cell death, which could make it
      a drug of choice for the treatment of cancer associated with hypertension. The
      goal of this research was to determine whether diltiazem is capable of inducing
      apoptosis in prostate cancer cells, either alone or in combination with the
      proteasome inhibitors, lactacystin and bortezomib (Velcade). Bortezomib is
      approved for the treatment of multiple myeloma; unfortunately, it has side
      effects that limit its utility. Presumably these side effects could be decreased
      by reducing its dose in combination with another drug. We have previously shown
      that lactacystin induces apoptosis in LNCaP cells; here, we show that this effect
      was enhanced by diltiazem. Furthermore, in proteasome inhibitor-resistant DU145
      cells, diltiazem alone did not induce apoptosis but decreased cytosolic calcium
      levels and induced mitochondrial fission; likewise, lactacystin did not induce
      apoptosis but up-regulated the proapoptotic protein Bik. However, increasing
      concentrations of diltiazem in combination with lactacystin or bortezomib induced
      apoptosis in a dose-dependent and synergistic manner. The combination of
      diltiazem and lactacystin also up-regulated the levels of Bik and released Bak
      from Bcl-xL, indicating the involvement of the Bcl2 family pathway in this
      apoptosis. In addition, the drug combination up-regulated GRP78, suggesting also
      the involvement of endoplasmic reticulum stress in the apoptotic response. Thus,
      our results demonstrate a potential therapeutic advantage of combining a
      frequently used calcium channel blocker with proteasome inhibitors in the
      treatment of prostate cancer.

PMID- 22393246
TI  - ABT-737 synergizes with bortezomib to induce apoptosis, mediated by Bid cleavage,
      Bax activation, and mitochondrial dysfunction in an Akt-dependent context in
      malignant human glioma cell lines.
AB  - We observed that glioma cells are differentially sensitive to N-{4-[4-(4'-chloro
      biphenyl-2-ylmethyl)-piperazin-1-yl]-benzoyl}-4-(3-dimethylamino-1
      phenylsulfanylmethyl-propylamino)-3-nitro-benzenesulfonamide (ABT-737) and
      administration of ABT-737 at clinically achievable doses failed to induce
      apoptosis. Although elevated Bcl-2 levels directly correlated with sensitivity to
      ABT-737, overexpression of Bcl-2 did not influence sensitivity to ABT-737. To
      understand the molecular basis for variable and relatively modest sensitivity to
      the Bcl-2 homology domain 3 mimetic drug ABT-737, the abundance of Bcl-2 family
      members was assayed in a panel of glioma cell lines. Bcl-2 family member
      proteins, Bcl-xL, Bcl-w, Mcl-1, Bax, Bak, Bid, and Noxa, were found to be
      expressed ubiquitously at similar levels in all cell lines tested. We then
      examined the contribution of other apoptosis-resistance pathways to ABT-737
      resistance. Bortezomib, an inhibitor of nuclear factor-kappaB (NF-kappaB), was
      found to enhance sensitivity of ABT-737 in phosphatase and tensin homolog on
      chromosome 10 (PTEN)-wild type, but not PTEN-mutated glioma cell lines. We
      therefore investigated the association between phosphatidylinositol 3-kinase
      (PI3K)/Akt activation and resistance to the combination of ABT-737 and bortezomib
      in PTEN-deficient glioma cells. Genetic and pharmacological inhibition of PI3K
      inhibition sensitized PTEN-deficient glioma cells to bortezomib- and ABT-737
      induced apoptosis by increasing cleavage of Bid protein, activation and
      oligomerization of Bax, and loss of mitochondrial membrane potential. Our data
      further suggested that PI3K/Akt-dependent protection may occur upstream of the
      mitochondria. This study demonstrates that interference with multiple apoptosis
      resistance signaling nodes, including NF-kappaB, Akt, and Bcl-2, may be required
      to induce apoptosis in highly resistant glioma cells, and therapeutic strategies
      that target the PI3K/Akt pathway may have a selective role for cancers lacking
      PTEN function.

PMID- 22393248
TI  - An inhibitor of neuronal exocytosis (DD04107) displays long-lasting in vivo
      activity against chronic inflammatory and neuropathic pain.
AB  - Small peptides patterned after the N terminus of the synaptosomal protein of 25
      kDa, a member of the protein complex implicated in Ca(2+)-dependent neuronal
      exocytosis, inhibit in vitro the release of neuromodulators involved in pain
      signaling, suggesting an in vivo analgesic activity. Here, we report that
      compound DD04107 (palmitoyl-EEMQRR-NH(2)), a 6-mer palmitoylated peptide that
      blocks the inflammatory recruitment of ion channels to the plasma membrane of
      nociceptors and the release of calcitonin gene-related peptide from primary
      sensory neurons, displays potent and long-lasting in vivo antihyperalgesia and
      antiallodynia in chronic models of inflammatory and neuropathic pain, such as the
      complete Freund's adjuvant, osteosarcoma, chemotherapy, and diabetic neuropathic
      models. Subcutaneous administration of the peptide produced a dose-dependent
      antihyperalgesic and antiallodynic activity that lasted >=24 h. The compound
      showed a systemic distribution, characterized by a bicompartmental
      pharmacokinetic profile. Safety pharmacology studies indicated that the peptide
      is largely devoid of side effects and substantiated that the in vivo activity is
      not caused by locomotor impairment. Therefore, DD04107 is a potent and long
      lasting antinociceptive compound that displays a safe pharmacological profile.
      These findings support the notion that neuronal exocytosis of receptors and
      neuronal algogens pivotally contribute to chronic inflammatory and neuropathic
      pain and imply a central role of peptidergic nociceptor sensitization to the
      pathogenesis of pain.

PMID- 22393249
TI  - Intrinsic oscillatory activity arising within the electrically coupled AII
      amacrine-ON cone bipolar cell network is driven by voltage-gated Na+ channels.
AB  - In the rd1 mouse model for retinal degeneration, the loss of photoreceptors
      results in oscillatory activity (~10-20 Hz) within the remnant electrically
      coupled network of retinal ON cone bipolar and AII amacrine cells. We tested the
      role of hyperpolarization-activated currents (I(h)), voltage-gated Na(+) channels
      and gap junctions in mediating such oscillatory activity. Blocking I(h) (1 mm
      Cs(+)) hyperpolarized the network and augmented activity, while antagonizing
      voltage-dependent Na(+) channels (1 MUm TTX) abolished oscillatory activity in
      the AII amacrine-ON cone bipolar cell network. Voltage-gated Na(+) channels were
      only observed in AII amacrine cells, implicating these cells as major drivers of
      activity. Pharmacologically uncoupling the network (200 MUm meclofenamic acid
      (MFA)) blocked oscillations in all cells indicating that Na(+) channels exert
      their influence over multiple cell types within the network. In wt retina,
      occluding photoreceptor inputs to bipolar cells (10 MUm NBQX and 50 MUm l-AP4)
      resulted in a mild (~10 mV) hyperpolarization and the induction of oscillatory
      activity within the AII amacrine-ON cone bipolar cell network. These oscillations
      had similar properties to those observed in rd1 retina, suggesting that no major
      degeneration-induced network rewiring is required to trigger spontaneous
      oscillations. Finally, we constructed a simplified computational model that
      exhibited Na(+) channel-dependent network oscillations. In this model, mild
      heterogeneities in channel densities between individual neurons reproduced our
      experimental findings. These results indicate that TTX-sensitive Na(+) channels
      in AII amacrine cells trigger degeneration-induced network oscillations, which
      provide a persistent synaptic drive to downstream remnant neurons, thus appearing
      to replace photoreceptors as the principal drivers of retinal activity.

PMID- 22393250
TI  - Investigation of the neuroanatomical substrates of reward seeking following
      protracted abstinence in mice.
AB  - Persistent vulnerability to relapse represents a major challenge in the treatment
      of drug addiction. The brain circuitry that underlies relapse-like behaviour can
      be investigated using animal models of drug seeking. As yet there have been no
      comprehensive brain mapping studies that have specifically examined the
      neuroanatomical substrates of cue-induced opiate seeking following abstinence in
      a mouse operant paradigm. The aim of this study was to compare the brain regions
      involved in sucrose vs. morphine seeking following protracted abstinence in mice.
      Male CD1 mice were trained to respond for either sucrose (10% w/v) or intravenous
      morphine (0.1 mg kg(-1) per infusion) in an operant paradigm in the presence of a
      discrete cue. Once stable responding was established, mice were subjected to
      abstinence in their home cages for 3 weeks and then perfused for tissue
      collection, or returned to the operant chambers to assess cue-induced reward
      seeking before being perfused for tissue collection. Brain tissue was processed
      for Fos immunohistochemistry and Fos expression was quantified in a range of
      brain nuclei. We identified unique patterns of neuronal activation for sucrose
      and morphine seeking mice as well as some overlap. Structures activated in both
      'relapse' groups included the anterior cingulate and orbitofrontal cortex,
      nucleus accumbens shell, bed nucleus of the stria terminalis, substantia nigra
      pars compacta, ventral tegmental area, hippocampus, periaqueductal grey, locus
      coeruleus and lateral habenula. Structures that were more activated in morphine
      seeking mice included the nucleus accumbens core, basolateral amygdala,
      substantia nigra pars reticulata, and the central nucleus of the amygdala. The
      dorsal raphe was the only structure examined that was specifically activated in
      sucrose seeking mice. Overall our findings support a cortico-striatal limbic
      circuit driving opiate seeking, and we have identified some additional circuitry
      potentially relevant to reward seeking following abstinence.

PMID- 22393251
TI  - Myostatin inhibition induces muscle fibre hypertrophy prior to satellite cell
      activation.
AB  - Muscle fibres are multinucleated post-mitotic cells that can change dramatically
      in size during adulthood. It has been debated whether muscle fibre hypertrophy
      requires activation and fusion of muscle stem cells, the satellite cells.
      Myostatin (MSTN) is a negative regulator of skeletal muscle growth during
      development and in the adult, and MSTN inhibition is therefore a potential
      therapy for muscle wasting diseases, some of which are associated with a
      depletion of satellite cells. Conflicting results have been obtained in previous
      analyses of the role of MSTN on satellite cell quiescence. Here, we inhibited
      MSTN in adult mice with a soluble activin receptor type IIB and analysed the
      incorporation of new nuclei using 5-bromo-2-deoxyuridine (BrdU) labelling by
      isolating individual myofibres. We found that satellite cells are activated by
      MSTN inhibition. By varying the dose and time course for MSTN inhibition,
      however, we found that myofibre hypertrophy precedes the incorporation of new
      nuclei, and that the overall number of new nuclei is relatively low compared to
      the number of total myonuclei. These results reconcile some of the previous work
      obtained by other methods. In contrast with previous reports, we also found that
      Mstn null mice do not have increased satellite cell numbers during adulthood and
      are not resistant to sarcopaenia. Our results support a previously proposed model
      of hypertrophy in which hypertrophy can precede satellite cell activation.
      Studies of the metabolic and functional effects of postnatal MSTN inhibition are
      needed to determine the consequences of increasing the cytoplasm/myonuclear ratio
      after MSTN inhibition.

PMID- 22393252
TI  - The motor cortex drives the muscles during walking in human subjects.
AB  - Indirect evidence that the motor cortex and the corticospinal tract contribute to
      the control of walking in human subjects has been provided in previous studies.
      In the present study we used coherence analysis of the coupling between EEG and
      EMG from active leg muscles during human walking to address if activity arising
      in the motor cortex contributes to the muscle activity during gait. Nine healthy
      human subjects walked on a treadmill at a speed of 3.5-4 km h(-1). Seven of the
      subjects in addition walked at a speed of 1 km h(-1). Significant coupling
      between EEG recordings over the leg motor area and EMG from the anterior tibial
      muscle was found in the frequency band 24-40 Hz prior to heel strike during the
      swing phase of walking. This signifies that rhythmic cortical activity in the 24
      40 Hz frequency band is transmitted via the corticospinal tract to the active
      muscles during walking. These findings demonstrate that the motor cortex and
      corticospinal tract contribute directly to the muscle activity observed in steady
      state treadmill walking.

PMID- 22393253
TI  - The role of a trigeminal sensory nucleus in the initiation of locomotion.
AB  - While we understand how stimuli evoke sudden, ballistic escape responses, like
      fish fast-starts, a precise pathway from sensory stimulation to the initiation of
      rhythmic locomotion has not been defined for any vertebrate. We have now asked
      how head skin stimuli evoke swimming in hatchling frog tadpoles. Whole-cell
      recordings and dye filling revealed a nucleus of ~20 trigeminal interneurons
      (tINs) in the hindbrain, at the level of the auditory nerve, with long,
      ipsilateral, descending axons. Stimulation of touch-sensitive trigeminal
      afferents with receptive fields anywhere on the head evoked large, monosynaptic
      EPSPs (~5-20 mV) in tINs, at mixed AMPAR/NMDAR synapses. Following stimuli
      sufficient to elicit swimming, tINs fired up to six spikes, starting 4-8 ms after
      the stimulus. Paired whole-cell recordings showed that tINs produce small (~2-6
      mV), monosynaptic, glutamatergic EPSPs in the hindbrain reticulospinal neurons
      (descending interneurons, dINs) that drive swimming. Modelling suggested that
      summation of EPSPs from 18-24 tINs can make 20-50% of dINs fire. We conclude
      that: brief activity in a few sensory afferents is amplified by recruitment of
      many tINs; these relay summating excitation to hindbrain reticulospinal dINs; dIN
      firing then initiates activity for swimming on the stimulated side. During
      fictive swimming, tINs are depolarised and receive rhythmic inhibition but do not
      fire. Our recordings demonstrate a neuron-by-neuron pathway from head skin
      afferents to the reticulospinal neurons and motoneurons that drive locomotion in
      a vertebrate. This direct pathway, which has an important amplifier function,
      implies a simple origin for the complex routes to initiate locomotion in higher
      vertebrates.

PMID- 22393254
TI  - Oxidant-induced cell death and Nrf2-dependent antioxidative response are
      controlled by Fra-1/AP-1.
AB  - AP-1 (Jun/Fos) transcription factors play key roles in various biological
      processes, including cell death. Here we report a novel role for Fra-1 in oxidant
      induced cell death controlled by modulating antioxidant gene expression. Fra-1
      deficient (Fra-1(Delta/Delta)) mouse embryonic fibroblasts (MEFs) and primary
      lung fibroblasts (PLFs) were remarkably resistant to H(2)O(2)- and diquat-induced
      cell death, compared to their wild-type (Fra-1(+/+)) counterparts. Fra-1
      deficiency ablated oxidant-induced mitochondrion-dependent apoptosis. Fra
      1(Delta/Delta) cells had elevated basal levels of antioxidant enzymes and
      intracellular glutathione (GSH), which were further stimulated by oxidants. Loss
      of Fra-1 led to an increased half-life of transcription factor Nrf2 and increased
      recruitment of this protein to the promoters of antioxidant genes and increased
      their expression. Depletion of intracellular GSH or RNA interference (RNAi)
      mediated knockdown of Nqo1, Hmox1, and Nrf2 restored oxidant-induced cell death
      in Fra-1(Delta/Delta) cells. Thus, Fra-1 appears to increase susceptibility to
      oxidants and promotes cell death by attenuating Nrf2-driven antioxidant
      responses.

PMID- 22393255
TI  - Caenorhabditis elegans dosage compensation regulates histone H4 chromatin state
      on X chromosomes.
AB  - Dosage compensation equalizes X-linked gene expression between the sexes. This
      process is achieved in Caenorhabditis elegans by hermaphrodite-specific, dosage
      compensation complex (DCC)-mediated, 2-fold X chromosome downregulation. How the
      DCC downregulates gene expression is not known. By analyzing the distribution of
      histone modifications in nuclei using quantitative fluorescence microscopy, we
      found that H4K16 acetylation (H4K16ac) is underrepresented and H4K20
      monomethylation (H4K20me1) is enriched on hermaphrodite X chromosomes in a DCC
      dependent manner. Depletion of H4K16ac also requires the conserved histone
      deacetylase SIR-2.1, while enrichment of H4K20me1 requires the activities of the
      histone methyltransferases SET-1 and SET-4. Our data suggest that the mechanism
      of dosage compensation in C. elegans involves redistribution of chromatin
      modifying activities, leading to a depletion of H4K16ac and an enrichment of
      H4K20me1 on the X chromosomes. These results support conserved roles for histone
      H4 chromatin modification in worm dosage compensation analogous to those seen in
      flies, using similar elements and opposing strategies to achieve differential 2
      fold changes in X-linked gene expression.

PMID- 22393256
TI  - Stable government of mitosis by Greatwall: the emperor's best servant.

PMID- 22393257
TI  - Nucleosome stability dramatically impacts the targeting of somatic hypermutation.
AB  - Somatic hypermutation (SHM) of immunoglobulin (Ig) genes is initiated by the
      activation-induced cytidine deaminase (AID). However, the influence of chromatin
      on SHM remains enigmatic. Our previous cell-free studies indicated that AID
      cannot access nucleosomal DNA in the absence of transcription. We have now
      investigated the influence of nucleosome stability on mutability in vivo. We
      introduced two copies of a high-affinity nucleosome positioning sequence (MP2)
      into a variable Ig gene region to assess its impact on SHM in vivo. The MP2
      sequence significantly reduces the mutation frequency throughout the nucleosome,
      and especially near its center, despite proportions of AID hot spots similar to
      those in Ig genes. A weak positioning sequence (M5) was designed based on rules
      deduced from published whole-genome analyses. Replacement of MP2 with M5 resulted
      in much higher mutation rates throughout the nucleosome. This indicates that both
      nucleosome stability and positioning significantly influence the SHM pattern. We
      postulate that, unlike RNA polymerase, AID has reduced access to stable
      nucleosomes. This study outlines the limits of nucleosome positioning for SHM of
      Ig genes and suggests that stable nucleosomes may need to be disassembled for
      access of AID. Possibly the variable regions of Ig genes have evolved for low
      nucleosome stability to enhance access to AID, DNA repair factors, and error
      prone polymerases and, hence, to maximize variability.

PMID- 22393258
TI  - The nucleosome binding protein HMGN1 interacts with PCNA and facilitates its
      binding to chromatin.
AB  - Proliferating cell nuclear antigen (PCNA) is a ubiquitous protein that interacts
      with multiple partners and regulates nuclear activities, including chromatin
      assembly, histone modifications, replication, and DNA damage repair. The role of
      specific partners in regulating PCNA activities is not fully understood. Here we
      identify the nucleosome binding protein HMGN1 as a new PCNA-interacting protein
      that enhances the binding of PCNA to chromatin but not to purified DNA. Two
      tetrapeptides in the conservative domain of HMGN1 contain amino acids necessary
      for the binding of HMGN1 to PCNA. Deletion of both tetrapeptides abolishes the
      HMGN1-PCNA interaction. PCNA preferentially binds to the linker DNA adjacent to
      an HMGN-containing nucleosome. In living cells, loss of HMGN1 decreases the rate
      of PCNA recruitment to damaged DNA sites. Our study identifies a new factor that
      facilitates the interaction of PCNA with chromatin and provides insights into
      mechanisms whereby nucleosome binding architectural proteins affect the cellular
      phenotype.

PMID- 22393260
TI  - A critical role for the Wnt effector Tcf4 in adult intestinal homeostatic self
      renewal.
AB  - Throughout life, intestinal Lgr5+ stem cells give rise to proliferating transient
      amplifying cells in crypts, which subsequently differentiate into one of the five
      main cell types and migrate along the crypt-villus axis. These dynamic processes
      are coordinated by a relatively small number of evolutionarily conserved
      signaling pathways, which includes the Wnt signaling pathway. The DNA-binding
      proteins of the T-cell factor family, Tcf1/Tcf7, Lef, Tcf3/Tcf7l1, and
      Tcf4/Tcf7l2, constitute the downstream effectors of the Wnt signaling pathway.
      While Tcf4 is the major member active during embryogenesis, the role of these Wnt
      effectors in the homeostasis of the adult mouse intestinal epithelium is
      unresolved. Using Tcf1-/-, Tcf3(flox), and novel Tcf4(flox) mice, we demonstrate
      an essential role for Tcf4 during homeostasis of the adult mouse intestine.

PMID- 22393259
TI  - Spatiotemporal localization of D-amino acid oxidase and D-aspartate oxidases
      during development in Caenorhabditis elegans.
AB  - Recent investigations have shown that a variety of D-amino acids are present in
      living organisms and that they possibly play important roles in physiological
      functions in the body. D-Amino acid oxidase (DAO) and D-aspartate oxidase (DDO)
      are degradative enzymes stereospecific for D-amino acids. They have been
      identified in various organisms, including mammals and the nematode
      Caenorhabditis elegans, although the significance of these enzymes and the
      relevant functions of D-amino acids remain to be elucidated. In this study, we
      investigated the spatiotemporal localization of C. elegans DAO and DDOs (DDO-1,
      DDO-2, and DDO-3) and measured the levels of several D- and L-amino acids in wild
      type C. elegans and four mutants in which each gene for DAO and the DDOs was
      partially deleted and thereby inactivated. Furthermore, several phenotypes of
      these mutant strains were characterized. The results reported in this study
      indicate that C. elegans DAO and DDOs are involved in egg-laying events and the
      early development of C. elegans. In particular, DDOs appear to play important
      roles in the development and maturation of germ cells. This work provides novel
      and useful insights into the physiological functions of these enzymes and D-amino
      acids in multicellular organisms.

PMID- 22393261
TI  - Plasma proteome dynamics: analysis of lipoproteins and acute phase response
      proteins with 2H2O metabolic labeling.
AB  - Understanding the pathologies related to the regulation of protein metabolism
      requires methods for studying the kinetics of individual proteins. We developed a
      (2)H(2)O metabolic labeling technique and software for protein kinetic studies in
      free living organisms. This approach for proteome dynamic studies requires the
      measurement of total body water enrichments by GC-MS, isotopic distribution of
      the tryptic peptide by LC-MS/MS, and estimation of the asymptotical number of
      deuterium incorporated into a peptide by software. We applied this technique to
      measure the synthesis rates of several plasma lipoproteins and acute phase
      response proteins in rats. Samples were collected at different time points, and
      proteins were separated by a gradient gel electrophoresis. (2)H labeling of
      tryptic peptides was analyzed by ion trap tandem mass spectrometry (LTQ MS/MS)
      for measurement of the fractional synthesis rates of plasma proteins. The high
      sensitivity of LTQ MS in zoom scan mode in combination with (2)H label
      amplification in proteolytic peptides allows detection of the changes in plasma
      protein synthesis related to animal nutritional status. Our results demonstrate
      that fasting has divergent effects on the rate of synthesis of plasma proteins,
      increasing synthesis of ApoB 100 but decreasing formation of albumin and
      fibrinogen. We conclude that this technique can effectively measure the synthesis
      of plasma proteins and can be used to study the regulation of protein homeostasis
      under physiological and pathological conditions.

PMID- 22393262
TI  - Glycomic and proteomic profiling of pancreatic cyst fluids identifies
      hyperfucosylated lactosamines on the N-linked glycans of overexpressed
      glycoproteins.
AB  - Pancreatic cancer is now the fourth leading cause of cancer deaths in the United
      States, and it is associated with an alarmingly low 5-year survival rate of 5%.
      However, a patient's prognosis is considerably improved when the malignant
      lesions are identified at an early stage of the disease and removed by surgical
      resection. Unfortunately, the absence of a practical screening strategy and
      clinical diagnostic test for identifying premalignant lesions within the pancreas
      often prevents early detection of pancreatic cancer. To aid in the development of
      a molecular screening system for early detection of the disease, we have
      performed glycomic and glycoproteomic profiling experiments on 21 pancreatic cyst
      fluid samples, including fluids from mucinous cystic neoplasms and intraductal
      papillary mucinous neoplasms, two types of mucinous cysts that are considered
      high risk to undergo malignant transformation. A total of 80 asparagine-linked (N
      linked) glycans, including high mannose and complex structures, were identified.
      Of special interest was a series of complex N-linked glycans containing two to
      six fucose residues, located predominantly as substituents on beta-lactosamine
      extensions. Following the observation of these "hyperfucosylated" glycans, bottom
      up proteomics experiments utilizing a label-free quantitative approach were
      applied to the investigation of two sets of tryptically digested proteins derived
      from the cyst fluids: 1) all soluble proteins in the raw samples and 2) a
      subproteome of the soluble cyst fluid proteins that were selectively enriched for
      fucosylation through the use of surface-immobilized Aleuria aurantia lectin. A
      comparative analysis of these two proteomic data sets identified glycoproteins
      that were significantly enriched by lectin affinity. Several candidate
      glycoproteins that appear hyperfucosylated were identified, including
      triacylglycerol lipase and pancreatic alpha-amylase, which were 20- and 22-fold
      more abundant, respectively, following A. aurantia lectin enrichment.

PMID- 22393263
TI  - How to dig deeper? Improved enrichment methods for mucin core-1 type
      glycopeptides.
AB  - Two different workflows were tested in order to develop methods that provide
      deeper insight into the secreted O-glycoproteome. Bovine serum samples were
      subjected to lectin affinity-chromatography both at the protein- and peptide
      level in order to selectively isolate glycopeptides with the most common, mucin
      core-1 sugar. This enrichment step was implemented with either protein-level
      mixed-bed ion-exchange chromatography or with peptide-level electrostatic
      repulsion hydrophilic interaction chromatography. Both methods led to at least
      65% of the identified products being glycopeptides, in comparison to ~ 25%
      without the additional chromatography steps [Darula, Z., and Medzihradszky, K. F.
      (2009) Affinity enrichment and characterization of mucin core-1 type
      glycopeptides from bovine serum. Mol. Cell. Proteomics 8, 2515-2526]. In order to
      improve not only the isolation but also the characterization of the glycopeptides
      exoglycosidases were used to eliminate carbohydrate extensions from the directly
      peptide-bound GalNAc units. Consequent tandem MS analysis of the mixtures using
      higher-energy collision-dissociation and electron-transfer dissociation led to
      the identification of 124 glycosylation sites in 51 proteins. While the electron
      transfer dissociation data provided the bulk of the information for both modified
      sequence and modification site assignment, the higher-energy collision
      dissociation data frequently yielded confirmation of the peptide identity, and
      revealed the presence of some core-2 or core-3 oligosaccharides. More than two
      thirds of the sites as well as the proteins have never been reported modified.

PMID- 22393265
TI  - Fiber delivered two-color picosecond source through nonlinear spectral
      transformation for coherent Raman scattering imaging.
AB  - We demonstrate a two-color, fiber-delivered picosecond source for coherent Raman
      scattering (CRS) imaging through nonlinear spectral transformation. The
      wavelength tunable picosecond pump is generated by nonlinear spectral compression
      of a prechirped femtosecond pulse in a fiber wavelength division multiplexer
      (WDM). The 1064-nm synchronized picosecond Stokes pulse is generated through
      pulse carving of a continuous wave laser, nonlinear spectral broadening in 100-m
      standard single-mode fiber, and subsequent dispersive compression with a fiber
      compressor. The pump and Stokes beams are combined and delivered by the fiber
      WDM. CRS imaging of mouse skin is performed to demonstrate the practicality of
      this source.

PMID- 22393264
TI  - Mapping protein surface accessibility via an electron transfer dissociation
      selectively cleavable hydrazone probe.
AB  - A protein's surface influences its role in protein-protein interactions and
      protein-ligand binding. Mass spectrometry can be used to give low resolution
      structural information about protein surfaces and conformations when used in
      combination with derivatization methods that target surface accessible amino acid
      residues. However, pinpointing the resulting modified peptides upon enzymatic
      digestion of the surface-modified protein is challenging because of the
      complexity of the peptide mixture and low abundance of modified peptides. Here a
      novel hydrazone reagent (NN) is presented that allows facile identification of
      all modified surface residues through a preferential cleavage upon activation by
      electron transfer dissociation coupled with a collision activation scan to
      pinpoint the modified residue in the peptide sequence. Using this approach, the
      correlation between percent reactivity and surface accessibility is demonstrated
      for two biologically active proteins, wheat eIF4E and PARP-1 Domain C.

PMID- 22393266
TI  - Temperature-modulated fluorescence tomography in a turbid media.
AB  - High scattering in biological tissues makes fluorescence tomography inverse
      problem very challenging in thick medium. We describe an approach termed
      "temperature-modulated fluorescence tomography" that can acquire fluorescence
      images at focused ultrasound resolution. By utilizing recently emerged
      temperature sensitive fluorescence contrast agents, this technique provides
      fluorescence images with high resolution prior to any reconstruction process. We
      demonstrate that this technique is well suited to resolve small fluorescence
      targets located several centimeters deep in tissue.

PMID- 22393267
TI  - Enhancing cancer therapeutics using size-optimized magnetic fluid hyperthermia.
AB  - Magnetic fluid hyperthermia (MFH) employs heat dissipation from magnetic
      nanoparticles to elicit a therapeutic outcome in tumor sites, which results in
      either cell death (>42  degrees C) or damage (<42  degrees C) depending on the
      localized rise in temperature. We investigated the therapeutic effect of MFH in
      immortalized T lymphocyte (Jurkat) cells using monodisperse magnetite (Fe(3)O(4))
      nanoparticles (MNPs) synthesized in organic solvents and subsequently transferred
      to aqueous phase using a biocompatible amphiphilic polymer. Monodisperse MNPs,
      ~16 nm diameter, show maximum heating efficiency, or specific loss power (watts/g
      Fe(3)O(4)) in a 373 kHz alternating magnetic field. Our in vitro results, for 15
      min of heating, show that only 40% of cells survive for a relatively low dose
      (490 MUg Fe/ml) of these size-optimized MNPs, compared to 80% and 90% survival
      fraction for 12 and 13 nm MNPs at 600 MUg Fe/ml. The significant decrease in cell
      viability due to MNP-induced hyperthermia from only size-optimized nanoparticles
      demonstrates the central idea of tailoring size for a specific frequency in order
      to intrinsically improve the therapeutic potency of MFH by optimizing both dose
      and time of application.

PMID- 22393268
TI  - Characteristic and magnetic field analysis of a high temperature superconductor
      axial-flux coreless induction maglev motor.
AB  - A new high temperature superconductor axial-flux coreless maglev motor (HTS AFIM)
      is proposed, of which the primary windings are made of HTS tapes and the
      secondary is a non-magnetic conductor. The main works of this paper are the
      magnetic-field computation and characteristics analysis of HTS AFIM. For the
      first one, the reduction of magnetic fields near outer and inner radius of the
      HTS AFIM is solved by introducing the sub-loop electro-magnetic model along the
      radial position. For the second one, the AC losses of HTS coils are calculated.
      The relationships between the device's characteristics and device parameters are
      presented, and the results indicate that under certain frequency and current
      levitation device can output enough lift force. The conclusions are verified by
      finite element calculations.

PMID- 22393269
TI  - On the Surface Mapping using Individual Cluster Impacts.
AB  - This paper describes the advantages of using single impacts of large cluster
      projectiles (e.g. C(60) and Au(400)) for surface mapping and characterization.
      The analysis of co-emitted time-resolved photon spectra, electron distributions
      and characteristic secondary ions shows that they can be used as surface
      fingerprints for target composition, morphology and structure. Photon, electron
      and secondary ion emission increases with the projectile cluster size and energy.
      The observed, high abundant secondary ion emission makes cluster projectiles good
      candidates for surface mapping of atomic and fragment ions (e.g., yield >1 per
      nominal mass) and molecular ions (e.g., few tens of percent in the 500 < m/z <
      1500 range).

PMID- 22393270
TI  - The effect of action video game experience on task-switching.
AB  - There is now a substantial body of work demonstrating that action video game
      experience results in enhancements in a wide variety of perceptual skills. More
      recently, several groups have also demonstrated improvements in abilities that
      are more cognitive in nature, in particular, the ability to efficiently switch
      between tasks. In a series of four experiments, we add to this body of work,
      demonstrating that the action video game player advantage is not exclusively due
      to an ability to map manual responses onto arbitrary buttons, but rather
      generalizes to vocal responses, is not restricted to tasks that are perceptual in
      nature (e.g. respond to a physical dimension of the stimulus such as its color),
      but generalizes to more cognitive tasks (e.g. is a number odd or even), and is
      present whether the switch requires a goal-switch or only a motor switch.
      Finally, a training study establishes that the relationship between the reduction
      in switch cost and action game playing is causal.

PMID- 22393271
TI  - Amelioration of ultraviolet-induced photokeratitis in mice treated with
      astaxanthin eye drops.
AB  - PURPOSE: Ultraviolet (UV) acts as low-dose ionizing radiation. Acute UVB exposure
      causes photokeratitis and induces apoptosis in corneal cells. Astaxanthin (AST)
      is a carotenoid, present in seafood, that has potential clinical applications due
      to its high antioxidant activity. In the present study, we examined whether
      topical administration of AST has preventive and therapeutic effects on UV
      photokeratitis in mice. METHODS: C57BL/6 mice were administered with AST diluted
      in polyethylene glycol (PEG) in instillation form (15 MUl) to the right eye. Left
      eyes were given vehicle alone as controls. Immediately after the instillation,
      the mice, under anesthesia, were irradiated with UVB at a dose of 400 mJ/cm2.
      Eyeballs were collected 24 h after irradiation and stained with H&E and TUNEL. In
      an in vitro study, mouse corneal epithelial (TKE2) cells were cultured with AST
      before UV exposure to quantify the UV-derived cytotoxicity. RESULTS: UVB exposure
      induced cell death and thinning of the corneal epithelium. However, the
      epithelium was morphologically well preserved after irradiation in AST-treated
      corneas. Irradiated corneal epithelium was significantly thicker in eyes treated
      with AST eye drops, compared to those treated with vehicles (p<0.01), in a doses
      dependent manner. Significantly fewer apoptotic cells were observed in AST
      treated eyes than controls after irradiation (p<0.01). AST also reduced oxidative
      stress in irradiated corneas. The in vitro study showed less cytotoxicity of TKE2
      cells in AST-treated cultures after UVB-irradiation (p<0.01). The cytoprotective
      effect increased with the dose of AST. CONCLUSIONS: Topical AST administration
      may be a candidate treatment to limit the damages by UV irradiation with wide
      clinical applications.

PMID- 22393272
TI  - A recurrent PAX6 mutation is associated with aniridia and congenital progressive
      cataract in a Chinese family.
AB  - PURPOSE: Aniridia is phenotyically and genetically heterogeneous. This study is
      to summarize the phenotypes and identify the genetic defect responsible for
      aniridia and congenital progressive cataract in a three generation Chinese
      family. METHODS: A detailed family history and clinical data from patients were
      collected by ophthalmologic examination, including visual acuity, slit-lamp
      examination, tonometer, keratometry, corneal topography, optical coherence
      tomography, and ultrasonic A/B scan. All exons and flanking intronic sequences of
      the paired box 6 (PAX6) gene were amplified by polymerase chain reaction (PCR)
      and screened for mutation by direct DNA sequencing. Structure and function of the
      mutant PAX6 were analyzed by bioinformatics analysis. RESULTS: All the six
      patients shared common manifestations of complete aniridia, congenital cataract
      and thickened cornea, and broad phenotypic variability was observed in nystagmus,
      ptosis, strabismus, glaucoma, corneal pannus, corneal curvature, corneal
      vascularization, cataract subtype, ectopia lentis, axial length, and optic disc
      anomalies. Sequencing of the candidate gene detected a heterozygous c.307C>T
      transition in the coding region of PAX6, resulting in the substitution of a
      highly conserved arginine codon for a termination codon (p.R103X). The p.P103X
      mutation co-segregated with the affected individuals in the family. The change
      was supposed to cause structural and functional changes based on computational
      analysis. CONCLUSIONS: We identified a recurrent PAX6 c.307C>T mutation in an
      aniridia and congenital progressive cataract family, and summarized the variable
      phenotypes among the patients, which expanded the phenotypic spectrum of aniridia
      in a different ethnic background.

PMID- 22393273
TI  - The FGF2 gene in a myopia animal model and human subjects.
AB  - PURPOSE: Fibroblast growth factor-2 (FGF2) has been implied in the development of
      myopia according to previous studies investigating FGF2 in the sclera and retinal
      pigment epithelium. This study measured retinal FGF2 gene expression in an animal
      model and also tested for the association between single nucleotide polymorphisms
      (SNPs) in FGF2 and high myopia. METHODS: The guinea pigs were assigned to 2
      groups: form deprivation myopia (FDM) for two weeks and normal control (free of
      form deprivation). Biometric measurement was performed and FGF2 expression levels
      were compared among the FDM eyes, the fellow eyes of the FDM group and the normal
      eyes in retina. We also enrolled 1,064 cases (<=-6.0 D) and 1,001 controls (>=
      1.5 D) from a Chinese population residing in Taiwan. Six tagging SNPs were
      genotyped to test for an association between genotypes and high myopia. RESULTS:
      The FDM eyes had the most prominent changes of refraction and axial length.
      Compared with the mRNA levels of FGF2 in the normal eyes, the FDM eyes had the
      highest levels of mRNA (p=0.0004) followed by the fellow eyes (p=0.002). The FDM
      and normal eyes became more myopic compared with the fellow eyes, but the fellow
      eyes became more hyperopic (p=0.004) in the end of the experiment which may be
      due to its relatively short axial length when compared with normal eyes (p=0.05).
      The SNP genotypes were all in Hardy-Weinberg equilibrium. However, none of the
      SNPs were significantly associated with high myopia (all p values >0.1).
      CONCLUSIONS: We identified a significant change of FGF2 expression in the FDM
      eyes but FGF2 genetic variants are unlikely to influence susceptibility to
      myopia. There may be a systemic effect to influence gene expression and
      refraction on the fellow eyes, which may perturb emmetropization in the fellow
      eyes. Our data also suggest using normal eyes rather than the fellow eyes as the
      control eyes when study the form deprivation myopia.

PMID- 22393274
TI  - Halofuginone down-regulates Smad3 expression and inhibits the TGFbeta-induced
      expression of fibrotic markers in human corneal fibroblasts.
AB  - PURPOSE: Due to its ability to disrupt transforming growth factor beta (TGF-beta)
      signaling, halofuginone has been successfully used to treat various fibrotic
      disorders. Here we investigated the antifibrotic potential of halofuginone in
      human corneal fibroblasts. METHODS: Human corneal fibroblasts were isolated from
      human donor corneas for in vitro experiments. TGF-beta was used to stimulate pro
      fibrotic responses from corneal fibroblasts under halofuginone treatment. The
      expression of alpha smooth muscle actin (alpha-SMA) and fibronectin was analyzed
      by western blots. Phalloidin toxin was used to stain cultures for stress fiber
      assemblies. Quantitative reverse transcription PCR (qRT-PCR) and immunostaining
      were used to analyze the expression of type I collagen mRNA and protein,
      respectively. The expression of Smad2, Smad3, phospho-Smad2, and phospho-Smad3
      was determined by western blots. RESULTS: Halofuginone was well tolerated by
      human corneal fibroblasts up to 10 ng/ml as demonstrated by a cell viability
      assay. At this concentration, TGF-beta-induced expression of the fibrotic markers
      alpha-SMA, fibronectin, and type I collagen was significantly reduced.
      Interestingly, under our experimental conditions, halofuginone treatment led to
      reduced protein expression of Smad3, which was both dose- and time-dependent.
      CONCLUSIONS: Our results suggest that halofuginone may exert its antifibrotic
      effects in the cornea via a novel molecular mechanism and may be used as an
      antifibrotic agent for corneal fibrosis treatment.

PMID- 22393275
TI  - Molecular analysis of the PAX6 gene for congenital aniridia in the Korean
      population: identification of four novel mutations.
AB  - PURPOSE: To analyze the paired box gene 6 (PAX6) in Korean patients with
      congenital aniridia. METHODS: Genomic DNA was isolated from peripheral blood
      leukocytes of 22 aniridia patients in 18 unrelated families. Polymerase chain
      reaction was performed for all 14 exons of PAX6 followed by bidirectional
      sequencing. RESULTS: Fourteen different kinds of mutations were detected in 16 of
      18 unrelated families (mutation detection rate: 88.9%), including four novel
      mutations; c.658G>T (p.Glu220*), c.464delG (p.Ser155Thrfs*52), c.87_90dupTGTA
      (p.Glu31Cysfs*26), and c.642A>C (p.Arg214Ser), among which the former three
      mutations induce premature termination of PAX6 protein translation. Approximately
      92.9% of identified mutations lead to the premature termination of the protein
      resulting from 7 nonsense mutations (50.0%), 3 splicing errors (21.4%), 2
      deletions (14.3%), and 1 insertion (7.1%). CONCLUSIONS: Most of the mutations
      identified in Korean aniridia patients lead to the premature truncation of the
      PAX6 protein, supporting that PAX6 protein haploinsufficiency causes the classic
      aniridia phenotype. We also found four novel PAX6 mutations associated with
      aniridia.

PMID- 22393276
TI  - Activation of sorbitol pathway in metabolic syndrome and increased susceptibility
      to cataract in Wistar-Obese rats.
AB  - PURPOSE: Obesity is a major public health problem worldwide, and of late,
      epidemiological studies indicate a preponderance of cataracts under obesity
      conditions. Although cataract is a multifactorial disorder and various
      biochemical mechanisms have been proposed, the influence of obesity on
      cataractogenesis has yet to be investigated. In such a scenario, a suitable
      animal model that develops cataract following the onset of obesity will be a
      welcome tool for biomedical research. Therefore, we investigated the molecular
      and biochemical basis for predisposition to cataract in the obese mutant rat
      models established in our institute because 15%-20% of these rats develop
      cataracts spontaneously as they reach 12-15 months of age. METHODS: We analyzed
      the major biochemical pathways in the normal lenses of different age groups of
      our obese mutant rat strains, Wistar/Obese (WNIN/Ob) and WNIN/GR-Ob, the former
      with euglycemia and the latter with an additional impaired glucose tolerance
      trait. In addition, sorbitol levels were estimated in the cataractous lenses of
      the obese rats. RESULTS: Except for the polyol pathway, all the principal
      pathways of the lens remained unaltered. Therefore, sorbitol levels were found to
      be high in the normal eye lenses of obese rats (WNIN/Ob and WNIN/GR-Ob) compared
      to their lean controls from three months of age onwards. Between WNIN/Ob and
      WNIN/GR-Ob, the levels of sorbitol were higher in the latter, suggesting a
      synergistic effect of impaired glucose tolerance along with obesity in the
      activation of the sorbitol pathway. Either way, an elevated sorbitol pathway
      seemed to be the predisposing factor responsible for cataract formation in these
      mutant rats. CONCLUSIONS: Activation of the sorbitol pathway indeed enhances the
      risk of cataract development in conditions such as metabolic syndrome. These rat
      models thus may be valuable tools for investigating obesity-associated cataract
      and for developing intervention strategies, based on these findings.

PMID- 22393277
TI  - Identification and study of a FBN1 gene mutation in a Chinese family with ectopia
      lentis.
AB  - PURPOSE: To identify the mutation in the fibrillin-1 gene (FBN1) in a Chinese
      family with ectopia lentis (EL) and to predict the structural and functional
      consequences of the mutation. METHODS: Patients and family members were given
      complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA was
      extracted from leukocytes of venous blood of three affected and three unaffected
      individuals in the family, and 100 healthy controls. All 65 coding exons and
      their flanking intronic boundaries of FBN1 were amplified in the proband by
      polymerase chain reaction, followed by direct sequencing. The mutation identified
      in the proband was screened for in other family members and 100 healthy controls
      by direct sequencing. Protein conservation analysis was performed in seven
      species using an online ClustalW tool. Protein structure was modeled based on the
      Protein data bank and mutated in PyMOL 1.1r1 to predict the structural and
      functional consequences of the mutation. RESULTS: A heterozygous c.2262A>G change
      in exon 18 of FBN1 was detected in the proband, which resulted in the
      substitution of tyrosine by cysteine at codon 754 (p.Y754C). This mutation was
      also present in the affected family members, but absent in other unaffected
      family members and 100 healthy controls. The mutant residue, located in the
      calcium binding epidermal growth factor-like7 domain, was highly conserved among
      mammalian species. The mutation could probably affect the disulfide bond
      formation of the domain and calcium binding of the adjacent domain, which would
      induce a critical functional change of the domain itself and neighboring domains.
      CONCLUSIONS: We indentified a p.Y754C mutation in FBN1, which is the causative
      mutation for EL in this family. This missense mutation introduced an additional
      cysteine residue by substitution of a highly conserved tyrosine residue within
      the cbEGF-like7 module.

PMID- 22393278
TI  - Lack of association between IL10 polymorphisms and sarcoidosis in Japanese
      patients.
AB  - PURPOSE: To investigate whether interleukin 10 (IL10) gene polymorphisms are
      associated with the development of sarcoidosis in Japanese patients. METHODS: Two
      hundred and eighty-eight Japanese sarcoidosis patients and 310 Japanese healthy
      controls were recruited. We genotyped 9 single-nucleotide polymorphisms in IL10
      and assessed the allelic diversity between cases and controls. RESULTS: No
      significant differences in the frequency of IL10 alleles, genotypes, and
      haplotypes in the sarcoidosis cases compared to the controls were detected.
      CONCLUSIONS: Our results suggest that IL10 polymorphisms are not significantly
      related to the pathogenesis of sarcoidosis in the Japanese population.

PMID- 22393279
TI  - Intraocular pressure reduction of fixed combination timolol maleate 0.5% and
      dorzolamide 2% (Cosopt) administered three times a day.
AB  - PURPOSE: To evaluate the safety and efficacy in intraocular pressure (IOP)
      reduction of increasing Cosopt dosage from twice to three times a day. METHODS:
      The study included patients with primary open-angle glaucoma or ocular
      hypertension. After a washout period, IOP was measured at baseline, after 4 weeks
      of treatment with Cosopt twice a day, and after another 4 weeks of treatment with
      Cosopt three times a day. Blood pressure, heart rate, and oxygen saturation
      levels were also recorded. RESULTS: Twenty-nine eyes of 29 patients were
      included. Increasing Cosopt dosage resulted in a statistically significant (P <
      0.001) additional reduction in IOP of 2.2 +/- 1.58 mmHg (10.69% +/- 7.49% of the
      baseline IOP values). There were no local or systemic adverse effects.
      CONCLUSION: Treatment with Cosopt three times a day was more effective in
      reducing IOP than twice a day, with no effect on safety.

PMID- 22393280
TI  - Pain and accuracy of focal laser treatment for diabetic macular edema using a
      retinal navigated laser (Navilas).
AB  - AIM: To investigate treatment-related pain and the accuracy of navigated laser
      photocoagulation in the treatment of clinically significant macular edema.
      METHODS: Focal laser treatment of diabetic macular edema in 54 consecutive
      patients was digitally planned on fundus images and performed using the navigated
      laser photocoagulation system Navilas((r)) (OD-OS GmbH, Teltow, Germany).
      Treatment-related pain was quantified on a visual analog scale directly after
      treatment and compared with a matched control group who received conventional
      laser treatment (n = 46). In addition, for Navilas-treated patients, the accuracy
      of spot placement on color images was analyzed 1 month after treatment. RESULTS:
      In total, 5423 laser spots (mean 100 per eye) were analyzed. With navigated
      treatment, 90% of laser spots were visible on color images, of which 96% were
      within 100 MUm from the target. Eighty percent of the laser spots were placed and
      visible within the 100 MUm target on an intention-to-treat basis for color
      imaging. Optical coherence topography confirmed that laser effects were limited
      to the outer retina. Treatment-related pain following navigated laser
      photocoagulation was significantly lower than that of conventional laser
      treatment (1.6 vs 4.4 on a visual analog scale, P < 0.001). CONCLUSION: Navigated
      laser effects could be visualized to a high percentage on post-treatment color
      images, and their location showed a high concordance to targeted areas. Patients
      reported that treatment-related pain following Navilas laser photocoagulation was
      significantly lower than pain following conventional laser treatment.

PMID- 22393281
TI  - Comparison of moderate and advanced glaucoma patients in Ghana.
AB  - PURPOSE: To compare moderate and advanced glaucoma patients in Ghana. METHODS: A
      retrospective cross-sectional study of 164 patients with primary open-angle
      glaucoma (POAG) were separated into moderate and advanced glaucoma groups.
      Definitions of moderate and advanced POAG were derived from International
      Geographical and Epidemiologic Ophthalmology criteria and included clinical
      assessment of optic disc atrophy and Humphrey automated perimetry. Data were
      collected at the patient's first visit prior to initiation of therapy. Eligible
      POAG patients included those >=30 years old with reliable Humphrey visual field
      (HVF) results, no past POAG diagnosis, treatment, or evidence of a secondary
      cause for glaucoma. Main outcome measures included comparisons of intraocular
      pressure (IOP), cup-to-disk ratio (CDR), best corrected visual acuity (VA), age,
      Humphrey mean deviation (MD), and pattern standard deviation (PSD). RESULTS: Of
      164 charts reviewed, 90 (54.9%) advanced and 74 (45.1%) moderate POAG patients
      were compared. Mean age was 59.36 versus 55.53 years, respectively. Significant
      differences in IOP, CDR, CDR asymmetry, and HVF results were described. IOP > 30
      mmHg was associated with CDR > 0.7 and MD greater than -12 dB in both eyes.
      CONCLUSION: Significant differences were found between IOP, CDR, MD and PSD
      values. HVF is predictive of pretreated IOP, CDR, and severity of POAG and it is
      strongly encouraged as part of the standard glaucoma work up in all Ghanaian
      patients.

PMID- 22393282
TI  - Successful closure of large blunt macular chorioretinal rupture: a case report.
AB  - The authors present a rare case of large chorioretinal rupture caused by blunt
      traumatic injury of the globe. A 22-year-old woman sustained a blunt injury to
      her left eye. The best-corrected Snellen visual acuity was 2/20 in her left eye,
      and hyphema and vitreous hemorrhage were noted. The day after the injury occurred
      the vitreous hemorrhage had disappeared. Fundus examination revealed a crescent
      shaped retinal rupture three disc diameters in size near the macula, and a
      choroidal rupture six disc diameters in size that was over the vascular arcade.
      Three days after the injury, vitrectomy with internal limiting membrane peeling
      was performed. Postoperative prone positioning was maintained for 4 days. Five
      days postoperatively, closure of the ruptured retina was confirmed. The visual
      acuity improved to 16/20 4 months after surgery and this was maintained over a 48
      month period. In conclusion, early vitrectomy with internal limiting membrane
      peeling after injury was effective for a case involving severe blunt
      chorioretinal rupture with closed globe injury.

PMID- 22393283
TI  - Effectiveness of influenza vaccine in aging and older adults: comprehensive
      analysis of the evidence.
AB  - Foremost amongst the diseases preventable by vaccination is influenza. Worldwide,
      influenza virus infection is associated with serious adverse events leading to
      hospitalization, debilitating complications, and death in elderly individuals.
      Immunization is considered to be the cornerstone for preventing these adverse
      health outcomes, and vaccination programs are timed to optimize protection during
      the annual influenza season. Trivalent inactivated influenza virus vaccines are
      believed to be both effective and cost-saving; however, in spite of widespread
      influenza vaccination programs, rates of hospitalization for acute respiratory
      illness and cardiovascular diseases have been increasing in this population
      during recent annual influenza seasons. From meta-analyses summarizing estimates
      of influenza vaccine effectiveness from available observational clinical studies,
      this review aims to examine how effective current influenza vaccine strategies
      are in the aging and older adult population and to analyze which are the most
      important biases that interfere with measurements of influenza vaccine
      effectiveness. Furthermore, consideration is given to strategies that should be
      adopted in order to optimize influenza vaccine effectiveness in the face of
      immune exhaustion.

PMID- 22393284
TI  - In vitro release and in vitro-in vivo correlation for silybin meglumine
      incorporated into hollow-type mesoporous silica nanoparticles.
AB  - BACKGROUND: The purpose of this study was to develop a sustained drug-release
      model for water-soluble drugs using silica nanoparticles. METHODS: Hollow-type
      mesoporous silica nanoparticles (HMSNs) were prepared using Na(2)CO(3) solution
      as the dissolution medium for the first time. The water-soluble compound, silybin
      meglumine, was used as the model drug. The Wagner-Nelson method was used to
      calculate the in vivo absorption fraction. RESULTS: The results of transmission
      electron microscopy and nitrogen adsorption revealed that the empty HMSNs had
      uniformly distributed particles of size 50-100 nm, a spherical appearance, a
      large specific surface area (385.89 +/- 1.12 m(2)/g), and ultralow mean pore size
      (2.74 nm). The highly porous structure allowed a large drug-loading rate (58.91%
      +/- 0.39%). In 0.08 M Na(2)CO(3) solution, silybin meglumine-loaded HMSNs could
      achieve highly efficacious and long-term sustained release for 72 hours in vitro.
      The results of in vitro-in vivo correlation revealed that HMSNs in 0.08 M
      Na(2)CO(3) solution had a correlation coefficient R(2) value of 0.9931, while
      those of artificial gastric juice and artificial intestinal juice were only
      0.9287 and 0.7689, respectively. CONCLUSION: The findings of in vitro-in vivo
      correlation indicate that HMSNs together with Na(2)CO(3) solution could achieve
      an excellent linear relationship between in vitro dissolution and in vivo
      absorption for 72 hours, leading to a promising model for sustained release of
      water-soluble drugs.

PMID- 22393285
TI  - Gambogic acid-loaded magnetic Fe(3)O(4) nanoparticles inhibit Panc-1 pancreatic
      cancer cell proliferation and migration by inactivating transcription factor
      ETS1.
AB  - BACKGROUND: E26 transformation-specific sequence-1 (ETS1) transcription factor
      plays important roles in both carcinogenesis and the progression of a wide range
      of malignancies. Aberrant ETS1 expression correlates with aggressive tumor
      behavior and a poorer prognosis in patients with various malignancies. The aim of
      the current study was to evaluate the efficacy of a drug delivery system
      utilizing gambogic acid-loaded magnetic Fe(3)O(4) nanoparticles (GA-MNP
      Fe(3)O(4)) on the suppression of ETS1-mediated cell proliferation and migration
      in Panc-1 pancreatic cancer cells. METHODS: The effects caused by GA-MNP
      Fe(3)O(4) on the proliferation of Panc-1 pancreatic cancer cells were evaluated
      using a MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay
      while inhibition of tumor cell migration was investigated in a scratch assay. The
      expressions of ETS1, cyclin D1, urokinase-type plasminogen activator (u-PA), and
      VEGF (vascular endothelial growth factor) were examined by Western blot to
      elucidate the possible mechanisms involved. RESULTS: In Panc-1 pancreatic cancer
      cells, we observed that application of GA-MNP-Fe(3)O(4) was able to suppress
      cancer cell proliferation and prevent cells from migrating effectively. After
      treatment, Panc-1 pancreatic cancer cells showed significantly decreased
      expression of ETS1, as well as its downstream target genes for cyclin D1, u-PA,
      and VEGF. CONCLUSION: Our novel finding reaffirmed the significance of ETS1 in
      the treatment of pancreatic cancer, and application of GA-MNP-Fe(3)O(4)
      nanoparticles targeting ETS1 should be considered as a promising contribution for
      better pancreatic cancer care.

PMID- 22393286
TI  - Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells
      through reactive oxygen species.
AB  - BACKGROUND: Zinc oxide nanoparticles (ZnO NPs) have received much attention for
      their implications in cancer therapy. It has been reported that ZnO NPs induce
      selective killing of cancer cells. However, the underlying molecular mechanisms
      behind the anticancer response of ZnO NPs remain unclear. METHODS AND RESULTS: We
      investigated the cytotoxicity of ZnO NPs against three types of cancer cells
      (human hepatocellular carcinoma HepG2, human lung adenocarcinoma A549, and human
      bronchial epithelial BEAS-2B) and two primary rat cells (astrocytes and
      hepatocytes). Results showed that ZnO NPs exert distinct effects on mammalian
      cell viability via killing of all three types of cancer cells while posing no
      impact on normal rat astrocytes and hepatocytes. The toxicity mechanisms of ZnO
      NPs were further investigated using human liver cancer HepG2 cells. Both the mRNA
      and protein levels of tumor suppressor gene p53 and apoptotic gene bax were
      upregulated while the antiapoptotic gene bcl-2 was downregulated in ZnO NP
      treated HepG2 cells. ZnO NPs were also found to induce activity of caspase-3
      enzyme, DNA fragmentation, reactive oxygen species generation, and oxidative
      stress in HepG2 cells. CONCLUSION: Overall, our data demonstrated that ZnO NPs
      selectively induce apoptosis in cancer cells, which is likely to be mediated by
      reactive oxygen species via p53 pathway, through which most of the anticancer
      drugs trigger apoptosis. This study provides preliminary guidance for the
      development of liver cancer therapy using ZnO NPs.

PMID- 22393287
TI  - Antimicrobial and osteogenic effect of Ag-implanted titanium with a
      nanostructured surface.
AB  - Ag-implanted titanium with a nanostructured surface was prepared by hydrothermal
      treatment with H(2)O(2) followed by Ag plasma immersion ion implantation.
      Streptococcus mutans, Porphyromonas gingivalis and Candida albicans were chosen
      for antimicrobial tests. Genes related to microbial structure or adhesion, namely
      glucan-binding proteins B (GbpB), fimbria protein A (FimA), and agglutinin-like
      sequence4 (Als4), were examined. The osteoblast's attachment, viability, and
      quantitative analysis of osteogenic gene expression (Alp, Ocn, RunX2) on titanium
      surfaces were evaluated. Scanning electron microscopy (SEM) revealed that Ag
      nanoparticles of approximately 10 nm were incorporated on the nanostructured
      surface of titanium after Ag plasma immersion ion implantation. Trials showed
      that 93.99% of S. mutans, 93.57% of P. g, and 89.78% of C. albicans were killed
      on the Ag-implanted titanium with a nanostructured surface. Gene expressions from
      the three microorganisms confirmed the antimicrobial activities of the Ag
      implanted titanium with a nanostructured surface. Furthermore, the adhesive
      images and viability assays indicated that the Ag-implanted titanium with a
      nanostructured surface did not impair osteoblasts. The expressions of osteoblast
      phenotype genes in cells grown on the Ag-implanted titanium surface were
      significantly increased. The results of this study suggest that the Ag-implanted
      titanium with a nanostructured surface displays good antimicrobial properties,
      reducing gene expressions of microorganisms, and excellent cell adhesion and
      osteogenic effects.

PMID- 22393288
TI  - Use of electroporation and reverse iontophoresis for extraction of transdermal
      multibiomarkers.
AB  - BACKGROUND: Monitoring of biomarkers, like urea, prostate-specific antigen (PSA),
      and osteopontin, is very important because they are related to kidney disease,
      prostate cancer, and ovarian cancer, respectively. It is well known that reverse
      iontophoresis can enhance transdermal extraction of small molecules, and even
      large molecules if reverse iontophoresis is used together with electroporation.
      Electroporation is the use of a high-voltage electrical pulse to create
      nanochannels within the stratum corneum, temporarily and reversibly. Reverse
      iontophoresis is the use of a small current to facilitate both charged and
      uncharged molecule transportation across the skin. The objectives of this in
      vitro study were to determine whether PSA and osteopontin are extractable
      transdermally and noninvasively and whether urea, PSA, and osteopontin can be
      extracted simultaneously by electroporation and reverse iontophoresis. METHODS:
      All in vitro experiments were conducted using a diffusion cell assembled with the
      stratum corneum of porcine skin. Three different symmetrical biphasic direct
      currents (SBdc), five various electroporations, and a combination of the two
      techniques were applied to the diffusion cell via Ag/AgCl electrodes. The three
      different SBdc had the same current density of 0.3 mA/cm(2), but different phase
      durations of 0 (ie, no current, control group), 30, and 180 seconds. The five
      different electroporations had the same pulse width of 1 msec and number of
      pulses per second of 10, but different electric field strengths of 0 (ie, no
      voltage, control group), 74, 148, 296, and 592 V/cm. Before and after each
      extraction experiment, skin impedance was measured at 20 Hz. RESULTS: It was
      found that urea could be extracted transdermally using reverse iontophoresis
      alone, and further enhancement of extraction could be achieved by combined use of
      electroporation and reverse iontophoresis. Conversely, PSA and osteopontin were
      found to be extracted transdermally only by use of reverse iontophoresis and
      electroporation with a high electrical field strength (> 296 V/cm). After
      application of reverse iontophoresis, electroporation, or a combination of the
      two techniques, a reduction in skin impedance was observed. CONCLUSION:
      Simultaneous transdermal extraction of urea, PSA, and osteopontin is possible
      only for the condition of applying reverse iontophoresis in conjunction with high
      electroporation.

PMID- 22393289
TI  - Nanobubbles for enhanced ultrasound imaging of tumors.
AB  - The fabrication and initial applications of nanobubbles (NBs) have shown
      promising results in recent years. A small particle size is a basic requirement
      for ultrasound contrast-enhanced agents that penetrate tumor blood vessel pores
      to allow for targeted imaging and therapy. However, the nanoscale size of the
      particles used has the disadvantage of weakening the imaging ability of clinical
      diagnostic ultrasound. In this work, we fabricated a lipid NBs contrast-enhanced
      ultrasound agent and evaluated its passive targeting ability in vivo. The results
      showed that the NBs were small (436.8 +/- 5.7 nm), and in vitro ultrasound
      imaging suggested that the ultrasonic imaging ability is comparable to that of
      microbubbles (MBs). In vivo experiments confirmed the ability of NBs to passively
      target tumor tissues. The NBs remained in the tumor area for a longer period
      because they exhibited enhanced permeability and retention. Direct evidence was
      obtained by direct observation of red fluorescence-dyed NBs in tumor tissue using
      confocal laser scanning microscopy. We have demonstrated the ability to fabricate
      NBs that can be used for the in vivo contrast-enhanced imaging of tumor tissue
      and that have potential for drug/gene delivery.

PMID- 22393290
TI  - A pH-sensitive multifunctional gene carrier assembled via layer-by-layer
      technique for efficient gene delivery.
AB  - BACKGROUND: The success of gene therapy asks for the development of
      multifunctional vectors that could overcome various gene delivery barriers, such
      as the cell membrane, endosomal membrane, and nuclear membrane. Layer-by-layer
      technique is an efficient method with easy operation which can be used for the
      assembly of multifunctional gene carriers. This work describes a pH-sensitive
      multifunctional gene vector that offered long circulation property but avoided
      the inhibition of tumor cellular uptake of gene carriers associated with the use
      of polyethylene glycol. METHODS: Deoxyribonucleic acid (DNA) was firstly
      condensed with protamine into a cationic core which was used as assembly
      template. Then, additional layers of anionic DNA, cationic liposomes, and o
      carboxymethyl-chitosan (CMCS) were alternately adsorbed onto the template via
      layer-by-layer technique and finally the multifunctional vector called CMCS
      cationic liposome-coated DNA/protamine/DNA complexes (CLDPD) was constructed. For
      in vitro test, the cytotoxicity and transfection investigation was carried out on
      HepG2 cell line. For in vivo evaluation, CMCS-CLDPD was intratumorally injected
      into tumor-bearing mice and the tumor cells were isolated for fluorescence
      determination of transfection efficiency. RESULTS: CMCS-CLDPD had ellipsoidal
      shapes and showed "core-shell" structure which showed stabilization property in
      serum and effective protection of DNA from nuclease degradation. In vitro and in
      vivo transfection results demonstrated that CMCS-CLDPD had pH-sensitivity and the
      outermost layer of CMCS fell off in the tumor tissue, which could not only
      protect CMCS- CLDPD from serum interaction but also enhance gene transfection
      efficiency. CONCLUSION: These results demonstrated that multifunctional CMCS
      CLDPD had pH- sensitivity, which may provide a new approach for the antitumor
      gene delivery.

PMID- 22393291
TI  - In vitro suppression of oral squamous cell carcinoma growth by ultrasound
      mediated delivery of curcumin microemulsions.
AB  - There is increasing interest in using natural products as anticancer agents, as
      many have antioxidative properties that may help to prevent cellular damage that
      can lead to cancer. In addition, there is the expectation that many natural
      products will have low toxicity and few side effects. However, most anticancer
      and antioxidative agents are hydrophobic, reducing their bioavailability in vivo
      and making them problematic to deliver. Curcumin provides a good model system for
      study. In low doses it shows both anticancer and antioxidation effects, whereas
      in high doses and delivered locally it could be cytotoxic for cancer cells. In
      this paper, curcumin microemulsions were formed with food-grade chemicals,
      including soybean lecithin, soybean oil, and Tween 80, a Food and Drug
      Administration-approved surfactant. The optimized composition formed curcumin
      microemulsions with a mean size of 40-50 nm, carrying a concentration of curcumin
      as high as 15 MUM. The stability of curcumin microemulsions refrigerated at 5
      degrees C over at least 968 days was assessed by size distribution and zeta
      potential. The effects of low-frequency ultrasound on two oral squamous cell
      carcinoma cell lines (OSCC-4 and OSCC-25), and the synergy between treatment with
      curcumin microemulsions and low-frequency sonic stimulation, were tested.
      Finally, microscopic imaging of the cells confirmed the toxic effects of the
      curcumin microemulsions, showing damaged and ruptured cells after treatment.
      Brief exposure to the curcumin-containing microemulsions did have cytotoxic
      effects, but the addition of ultrasound strongly enhanced those effects,
      especially on OSCC-25 cells.

PMID- 22393293
TI  - Treating glioblastoma multiforme with selective high-dose liposomal doxorubicin
      chemotherapy induced by repeated focused ultrasound.
AB  - BACKGROUND: High-dose tissue-specific delivery of therapeutic agents would be a
      valuable clinical strategy. We have previously shown that repeated transcranial
      focused ultrasound is able to increase the delivery of Evans blue significantly
      into brain tissue. The present study shows that repeated pulsed high-intensity
      focused ultrasound (HIFU) can be used to deliver high-dose atherosclerotic plaque
      specific peptide-1 (AP-1)-conjugated liposomes selectively to brain tumors.
      METHODS: Firefly luciferase (Fluc)-labeled human GBM8401 glioma cells were
      implanted into NOD-scid mice. AP-1-conjugated liposomal doxorubicin or liposomal
      doxorubicin alone was administered followed by pulsed HIFU and the doxorubicin
      concentration in the treated brains quantified by fluorometer. Growth of the
      labeled glioma cells was monitored through noninvasive bioluminescence imaging
      and finally the brain tissue was histologically examined after sacrifice.
      RESULTS: Compared with the control group, the animals treated with 5 mg/kg
      injections of AP-1 liposomal doxorubicin or untargeted liposomal doxorubicin
      followed by repeated pulsed HIFU not only showed significantly enhanced
      accumulation of drug at the sonicated tumor site but also a significantly
      elevated tumor-to-normal brain drug ratio (P < 0.001). Combining repeated pulsed
      HIFU with AP-1 liposomal doxorubicin or untargeted liposomal doxorubicin has
      similar antitumor effects. CONCLUSION: This study demonstrates that targeted or
      untargeted liposomal doxorubicin, followed by repeated pulsed HIFU, is a
      promising high-dose chemotherapy method that allows the desired brain tumor
      region to be targeted specifically.

PMID- 22393292
TI  - Enhanced cellular uptake of aminosilane-coated superparamagnetic iron oxide
      nanoparticles in mammalian cell lines.
AB  - PURPOSE: To compare the cellular uptake efficiency and cytotoxicity of
      aminosilane (SiO(2)-NH(2))-coated superparamagnetic iron oxide (SPIO@SiO(2)
      NH(2)) nanoparticles with three other types of SPIO nanoparticles coated with
      SiO(2) (SPIO@SiO(2)), dextran (SPIO@dextran), or bare SPIO in mammalian cell
      lines. MATERIALS AND METHODS: Four types of monodispersed SPIO nanoparticles with
      a SPIO core size of 7 nm and an overall size in a range of 7-15 nm were
      synthesized. The mammalian cell lines of MCF-7, MDA-MB-231, HT-29, RAW264.7,
      L929, HepG2, PC-3, U-87 MG, and mouse mesenchymal stem cells (MSCs) were
      incubated with four types of SPIO nanoparticles for 24 hours in the serum-free
      culture medium Dulbecco's modified Eagle's medium (DMEM) with 4.5 MUg/mL iron
      concentration. The cellular uptake efficiencies of SPIO nanoparticles were
      compared by Prussian blue staining and intracellular iron quantification. In
      vitro magnetic resonance imaging of MSC pellets after SPIO labeling was performed
      at 3 T. The effect of each SPIO nanoparticle on the cell viability of RAW 264.7
      (mouse monocyte/macrophage) cells was also evaluated. RESULTS: Transmission
      electron microscopy demonstrated surface coating with SiO(2)-NH(2), SiO(2), and
      dextran prevented SPIO nanoparticle aggregation in DMEM culture medium. MCF-7,
      MDA-MB-231, and HT-29 cells failed to show notable iron uptake. For all the
      remaining six cell lines, Prussian blue staining and intracellular iron
      quantification demonstrated that SPIO@ SiO(2)-NH(2) nanoparticles had the highest
      cellular uptake efficiency. SPIO@SiO(2)-NH(2), bare SPIO, and SPIO@dextran
      nanoparticles did not affect RAW 264.7 cell viability up to 200 MUg Fe/mL, while
      SPIO@SiO(2) reduced RAW 264.7 cell viability from 10 to 200 MUg Fe/mL in a dose
      dependent manner. CONCLUSION: Cellular uptake efficiency of SPIO nanoparticles
      depends on both the cell type and SPIO surface characteristics. Aminosilane
      surface coating enhanced the cellular uptake efficiency without inducing
      cytotoxicity in a number of cell lines.

PMID- 22393294
TI  - Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells
      upon encapsulation into biocompatible nanoparticles.
AB  - Among numerous drug-delivery approaches, reconstituted high-density lipoprotein
      (rHDL) nanocarriers have proven particularly applicable for delivering highly
      hydrophobic drugs. In this study, we have investigated the enhancement of the
      therapeutic impact of valrubicin (AD-32), an antineoplastic agent that has been
      limited to intravesicular application against bladder cancer, despite the
      encouraging original preclinical data. Earlier studies validated the superior
      therapeutic efficacy of AD-32 over doxorubicin. In the present study, rHDL/AD-32
      nanoparticles were formulated and characterized with regard to encapsulation
      efficiency, physicochemical properties, selective toxicity, and receptor-mediated
      uptake. The half maximal inhibitory concentration values (IC(50)) for rHDL/AD-32
      nanoparticles were 1.8 and 2.6 times lower than the free AD-32 for prostate (PC
      3) and ovarian (SKOV-3) cancer cell lines, respectively, whereas nonmalignant
      cell lines demonstrated 5 and 1.48 times higher IC(50) doses with rHDL/AD-32
      formulations. The data obtained demonstrated effective receptor- mediated uptake
      of AD-32 from the rHDL nanocarriers by PC-3 and SKOV-3 cancer cells via a
      targeted drug-delivery process. The rHDL/AD-32 formulation was stable for 6
      months when stored at 4 degrees C or at -20 degrees C, as 92% of the AD-32 was
      retained in the nanoparticles. The findings from this study show that the rHDL/AD
      32 formulation can overcome the solubility barriers of AD-32 and thus serve as an
      effective systemically administered chemotherapeutic agent.

PMID- 22393295
TI  - Novel microfilaricidal activity of nanosilver.
AB  - PURPOSE: The currently available drug repertoire against lymphatic filariasis, a
      major health hazard in the developing world, is inadequate and is fraught with
      serious limitations. Thus, the development of an effective antifilarial strategy
      has become a global research thrust mandated by the World Health Organization.
      Nanoparticles of silver endowed with antibacterial potency are known to induce
      apoptosis in eukaryotic cells. The present study was designed to investigate the
      possible microfilaricidal efficacy of silver nanoparticles and to establish the
      validity of apoptotic rationale in antifilarial drug designing. METHODS: This
      report analyzed the effect of nanoparticles of silver as well as gold (size
      range: 10-15 nm) on the microfilariae of Brugia malayi obtained from the lavage
      of peritoneal cavities of infected jirds (Meriones unguiculatus). The study
      included a microfilarial motility assay, a trypan blue exclusion test, a
      poly(adenosine diphosphate-ribose) polymerase activity study, ethidium
      bromide/acridine orange differential staining, and transmission, as well as
      scanning electron microscopic evaluation of ultrastructural changes in
      microfilariae. RESULTS: The study demonstrates that nanoparticles of silver, but
      not of gold, elicited significant loss in microfilarial motility. Differential
      staining of parasites with ethidium bromide and acridine orange, poly(adenosine
      diphosphate-ribose) polymerase activity in microfilarial lysate, and electron
      microscopic findings underscored apoptotic death of parasites attributable to
      nanosilver. In a trypan blue exclusion test, the 50% lethal dose of nanosilver
      was measured to be 101.2 MUM, which was higher than the recorded complete
      inhibitory concentration value (50.6 MUM), thus supporting nanosilver as a
      potential drug candidate against lymphatic filariasis. CONCLUSION: The present
      report provides the first ever conclusive proof in support of apoptosis as a
      novel stratagem in antifilarial drug designing and nanoscale silver as a valid
      lead in research on antifilarial therapeutics. The main embargo about the current
      drug diethylcarbamazine citrate is its empirical use without rationale. Effective
      microfilaricidal activity of nanosilver at relatively low concentrations as
      reported in this study, with evidence of the induction of apoptosis in
      microfilariae, projects nanosilver as a potential drug adjuvant against lymphatic
      filariasis. The much higher 50% lethal dose value of nanosilver compared to the
      complete inhibitory concentration value reported in this study argues in favor of
      a safe therapeutic window of this agent in its antifilarial efficacy.

PMID- 22393296
TI  - Enhancing the specificity and efficiency of polymerase chain reaction using
      polyethyleneimine-based derivatives and hybrid nanocomposites.
AB  - There is a general necessity to improve the specificity and efficiency of the
      polymerase chain reaction (PCR), and exploring the PCR-enhancing mechanism still
      remains a great challenge. In this paper we report the use of branched
      polyethyleneimine (PEI)-based derivatives and hybrid nanocomposites as a novel
      class of enhancers to improve the specificity and efficiency of a nonspecific PCR
      system. We show that the surface-charge polarity of PEI and PEI derivatives plays
      a major role in their effectiveness to enhance the PCR. Positively charged amine
      terminated pristine PEI, partially (50%) acetylated PEI (PEI-Ac(50)), and
      completely acetylated PEI (PEI-Ac) are able to improve PCR efficiency and
      specificity with an optimum concentration order of PEI < PEI-Ac(50) < PEI-Ac,
      whereas negatively charged carboxyl-terminated PEI (PEI-SAH; SAH denotes
      succinamic acid groups) and neutralized PEI modified with both polyethylene
      glycol (PEG) and acetyl (Ac) groups (PEI-PEG-Ac) are unable to improve PCR
      specificity and efficiency even at concentrations three orders of magnitude
      higher than that of PEI. Our data clearly suggests that the PCR-enhancing effect
      is primarily based on the interaction between the PCR components and the PEI
      derivatives, where electrostatic interaction plays a major role in concentrating
      the PCR components locally on the backbones of the branched PEI. In addition,
      multiwalled carbon nanotubes modified with PEI and PEI-stabilized gold
      nanoparticles are also able to improve the PCR specificity and efficiency with an
      optimum PEI concentration less than that of the PEI alone, indicating that the
      inorganic component of the nanocomposites may help improve the interaction
      between PEI and the PCR components. The developed PEI-based derivatives or
      nanocomposites may be used as efficient additives to enhance other PCR systems
      for different biomedical applications.

PMID- 22393297
TI  - Mannosylated liposomes for targeted gene delivery.
AB  - BACKGROUND: Liposomes can be modified with different ligands to control their
      biological properties, such as longevity, targeting ability, and intracellular
      penetration, in a desired fashion. The aim of this study was to modify liposomes
      with a novel mannosylated polyethylene glycol-phosphatidylethanolamine (M-PEG-PE)
      ligand to achieve active targeted gene delivery. METHODS: Rat Kupffer cells were
      isolated and used as model cells for in vitro evaluation of cytotoxicity and
      transfection efficiency. The modified liposomes were intravenously injected into
      the rats, and Kupffer cells were isolated and analyzed by flow cytometry for in
      vivo gene delivery and expression. RESULTS: The M-PEG-PE-modified liposome
      enhanced green fluorescence protein plasmid (M-PEG-PE-Lipo-pEGFP) complexes had a
      particle size of 237 nm and a loading efficiency of 90%. The M-PEG-PE-Lipo-pEGFP
      complexes displayed remarkably higher transfection efficiency than unmodified
      Lipo-pEGFP, both in vitro (51%-30%) and in vivo (43%-27%). CONCLUSION: M-PEG-PE
      could function as an excellent active targeting ligand, and M-PEG-PE-modified
      liposomes could be promising active targeted drug delivery vectors.

PMID- 22393298
TI  - Oral antiplatelet therapy for atherothrombotic disease: overview of current and
      emerging treatment options.
AB  - Clinical presentations of atherothrombotic vascular disease, such as acute
      coronary syndromes, ischemic stroke or transient ischemic attack, and symptomatic
      peripheral arterial disease, are major causes of morbidity and mortality
      worldwide. Platelet activation and aggregation play a seminal role in the
      arterial thrombus formation that precipitates acute manifestations of
      atherothrombotic disease. As a result, antiplatelet therapy has become the
      cornerstone of therapy for the prevention and treatment of atherothrombotic
      disease. Dual antiplatelet therapy with aspirin and a P2Y(12) adenosine
      diphosphate (ADP) receptor inhibitor, such as clopidogrel or prasugrel, is the
      current standard-of-care antiplatelet therapy in patients with acute coronary
      syndromes managed with an early invasive strategy. However, these agents are
      associated with several important clinical limitations, including significant
      residual risk for ischemic events, bleeding risk, and variability in the degree
      of platelet inhibition. The residual risk can be attributed to the fact that
      aspirin and P2Y(12) inhibitors block only the thromboxane A(2) and ADP platelet
      activation pathways but do not affect the other pathways that lead to thrombosis,
      such as the protease-activated receptor-1 pathway stimulated by thrombin, the
      most potent platelet agonist. Bleeding risk associated with aspirin and P2Y(12)
      inhibitors can be explained by their inhibitory effects on the thromboxane A(2)
      and ADP pathways, which are critical for protective hemostasis. Interpatient
      variability in the degree of platelet inhibition in response to antiplatelet
      therapy may have a genetic component and contribute to poor clinical outcomes.
      These considerations underscore the clinical need for therapies with a novel
      mechanism of action that may reduce ischemic events without increasing the
      bleeding risk.

PMID- 22393299
TI  - Sudden death in eating disorders.
AB  - Eating disorders are usually associated with an increased risk of premature death
      with a wide range of rates and causes of mortality. "Sudden death" has been
      defined as the abrupt and unexpected occurrence of fatality for which no
      satisfactory explanation of the cause can be ascertained. In many cases of sudden
      death, autopsies do not clarify the main cause. Cardiovascular complications are
      usually involved in these deaths. The purpose of this review was to report an
      update of the existing literature data on the main findings with respect to
      sudden death in eating disorders by means of a search conducted in PubMed. The
      most relevant conclusion of this review seems to be that the main causes of
      sudden death in eating disorders are those related to cardiovascular
      complications. The predictive value of the increased QT interval dispersion as a
      marker of sudden acute ventricular arrhythmia and death has been demonstrated.
      Eating disorder patients with severe cardiovascular symptoms should be
      hospitalized. In general, with respect to sudden death in eating disorders, some
      findings (eg, long-term eating disorders, chronic hypokalemia, chronically low
      plasma albumin, and QT intervals >600 milliseconds) must be taken into account,
      and it must be highlighted that during refeeding, the adverse effects of
      hypophosphatemia include cardiac failure. Monitoring vital signs and performing
      electrocardiograms and serial measurements of plasma potassium are relevant
      during the treatment of eating disorder patients.

PMID- 22393300
TI  - Assessment of coronary heart diseases in diabetics in al-Madinah al-Munawarah.
AB  - BACKGROUND: Coronary heart disease is highly prevalent and a major cause of
      morbidity and mortality in diabetic patients. The aim of this study was to assess
      the major risk factors and their predictor score for coronary heart diseases in
      diabetic patients. METHODS: The present study was conducted in al-Madinah,
      Kingdom of Saudi Arabia. Using a cross-sectional case control study, 262
      outpatient diabetics and 264 matched control subjects were examined for the risk
      factors and risk predictor scores for ischemic heart disease. The mean age of the
      patient and control groups was 49.61 +/- 12.93 years and 48.39 +/- 11.60 years,
      respectively. RESULTS: Diabetic patients had significantly higher positive family
      history of diabetes, but no significant difference regarding their family history
      of hypertension. There was a significantly higher body mass index (33.67
      kg/m(2)), glycosylated hemoglobin (7.26%), significantly higher cholesterol, low
      density lipoprotein, and triglyceride in diabetics compared to control. Diabetic
      patients had higher risk for developing coronary heart disease with a mean risk
      score of 6.07 while the control subject risk score was -6.81. However, females
      showed significantly higher risk for coronary heart diseases than did males.
      CONCLUSION: Our study replicates the known fact of higher risk in diabetes, but
      higher risk of coronary heart disease in female diabetics compared with male
      diabetics.

PMID- 22393301
TI  - Fourth-generation spinal instrumentation: experience with adolescent idiopathic
      scoliosis at a tertiary care hospital in Pakistan.
AB  - OBJECTIVE: To evaluate the radiological and functional outcome of surgical
      treatment of adolescent idiopathic scoliosis using fourth-generation posterior
      spinal instrumentation at The Aga Khan University, Karachi, Pakistan. DESIGN:
      Case series. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital after
      a minimum of 2 years postoperatively. PATIENTS AND METHODS: A total of 20
      patients with adolescent idiopathic scoliosis were recruited into the study and
      evaluated for radiological and functional outcome. The study period was from 2000
      to 2005. Radiological outcome was assessed using Cobb angle measurement pre and
      postoperatively, hence assessing percentage correction. The lower instrumented
      vertebra was taken as the neutral vertebra and the level was recorded. Functional
      outcome was determined using the Scoliosis Research Society patient administered
      questionnaire. All patients were called to the clinic and asked to fill in the
      form. Those patients who were out of the city were mailed the forms and requested
      via telephone to complete and return. RESULTS: Of the 20 patients operated on,
      twelve were female and eight were male. The average age at operation was 12.7
      years. The mean Cobb angle was 69 degrees  preoperatively and 20 degrees 
      postoperatively, representing a percentage correction of 71%. The average
      duration of follow-up was 3.6 years. There was one major complication involving
      neurological injury post-op and two minor complications involving wound
      infection. The average Scoliosis Research Society score (on a scale of 1-5, with
      5 being best) for pain was 4.5, self-image was 4.2, functional status was 4.1,
      mental status was 3.8, and satisfaction was 4.4. There was no relationship
      between the percentage correction of scoliosis and the functional outcome. Those
      patients with a high preoperative Cobb angle tended to have a better outcome for
      functional and mental status postoperatively. There was no relation between the
      lower instrumented vertebra and functional outcome. CONCLUSION: In the correct
      indications, fourth-generation posterior instrumentation and fusion is a reliable
      and satisfactory technique to treat adolescent idiopathic scoliosis.

PMID- 22393302
TI  - Treatment of gastric phytobezoars with Coca-Cola given via oral route: a case
      report.
AB  - BACKGROUND: A 43-year-old female patient presented with a chief complaint of
      upper abdominal pain. As her complaints had lasted for 1 month, an upper
      gastrointestinal system endoscopy was performed and discovered a bezoar in the
      stomach. CASE PRESENTATION: The bezoar was quite hard and light green-yellow in
      color. Pathological examination revealed phytobezoar. The patient was
      hospitalized and given oral Coca-Cola((r)) Zero for seven days at a dose of 500
      mL three times daily. CONCLUSION: The upper gastrointestinal system endoscopy
      performed at the end of 7 days showed that the phytobezoar had softened and
      become smaller. The phytobezoar was broken into pieces with biopsy forceps and
      washing was applied, so the phytobezoar pieces could pass through the pylorus.
      The patient was discharged after the procedure without problem.

PMID- 22393304
TI  - Prevalence and risk factors for cervical squamous intraepithelial lesions among
      women infected with HIV-1 in Makurdi, Nigeria.
AB  - BACKGROUND: The purpose of this study was to determine the prevalence and risk
      factors for cervical squamous intraepithelial lesions (SIL) among women infected
      with human immunodeficiency virus type 1 (HIV-1) receiving care at the Federal
      Medical Center Makurdi, Nigeria. METHODS: Between March and December 2009, a
      total of 253 women infected with HIV-1 had cervical smears taken for cytology.
      HIV-1 RNA viral load and CD4 counts were also measured. RESULTS: Of the 253
      women, cervical SIL were present in 45 (17.8%). However, abnormal cervical
      cytology was noted in 146 (57.7%). Of those with abnormal cervical cytology, 101
      (39.9%) women had atypical squamous cells of undetermined significance, 16 (6.3%)
      had low-grade SIL, and 29 (11.5%) women had high-grade SIL. The median CD4
      lymphocyte count was lower in participants with cervical SIL compared with those
      without (132 versus 184 cells/mm(3); P = 0.03). The median HIV-1 RNA viral load
      was higher in women with cervical SIL (102,705 versus 64,391 copies/mL; P =
      0.02). A CD4 lymphocyte count of <200 cells/mm(3) and an HIV-1 RNA viral load of
      <10,000 copies/mL were found to be significantly associated with cervical SIL.
      CONCLUSION: A high prevalence of cervical SIL was found among HIV-1-infected
      women in Makurdi, Nigeria. Increased immune suppression and HIV-1 viremia are
      significantly associated with cervical SIL.

PMID- 22393305
TI  - Correlation between aromatase expression in the eutopic endometrium of
      symptomatic patients and the presence of endometriosis.
AB  - OBJECTIVE: To investigate whether aromatase expression in the eutopic endometrium
      correlates with the presence and severity of endometriosis in patients with
      infertility and/or dysmenorrhea undergoing laparoscopy and hysteroscopy.
      PATIENTS: The study involved 106 patients of reproductive age with symptoms of
      dysmenorrhea and infertility. Sixteen endometriosis-free asymptomatic patients
      were used as a control group. METHODS: Concomitant laparoscopy and hysteroscopy
      was carried out in all cases. An endometrial biopsy was taken to determine
      aromatase p450 expression by immunohistochemistry. Endometriosis was staged
      according to the American Society of Reproductive Medicine classification.
      RESULTS: Endometriosis was diagnosed by laparoscopy in 92/106 symptomatic
      patients. In this group, aromatase expression was detected in the eutopic
      endometrium of 66/92 patients with endometriosis (72%) and in 13/14 (95%)
      patients in the symptomatic, endometriosis-free group (P = 0.09). Aromatase
      expression was not detected in any patients from the control group. In the
      endometriosis group, aromatase expression was detected in the eutopic endometrium
      of 28/45 patients (62%) with American Society of Reproductive Medicine
      classification stage 1 of the disease, in 11/14 patients (78%) with stage II,
      14/20 patients (70%) with stage III, and in 12/13 patients (92%) with stage IV;
      however, the difference was only statistically significant between stages I and
      IV (P = 0.04). CONCLUSION: Aromatase expression in the endometrium was associated
      with the presence of dysmenorrhea and infertility irrespective of the presence of
      endometriosis. When endometriosis was present, however, there was a tendency for
      aromatase expression to be positively correlated with dysmenorrhea severity.

PMID- 22393303
TI  - Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with
      streptococcal infections (PANDAS): an overview.
AB  - Lyme disease (LD) is a complex, multisystemic illness. As the most common vector-
      borne disease in the United States, LD is caused by bacterial spirochete Borrelia
      burgdorferi sensu stricto, with potential coinfections from agents of
      anaplasmosis, babesiosis, and ehrlichiosis. Persistent symptoms and clinical
      signs reflect multiorgan involvement with episodes of active disease and periods
      of remission, not sparing the coveted central nervous system. The capability of
      microorganisms to cause and exacerbate various neuropsychiatric pathology is also
      seen in pediatric autoimmune neuropsychiatric disorders associated with
      streptococcal infections (PANDAS), a recently described disorder attributed to
      bacterium Streptococcus pyogenes of group A beta-hemolytic streptococcus in which
      neurologic tics and obsessive-compulsive disorders are sequelae of the infection.
      In the current overview, LD and PANDAS are juxtaposed through a review of their
      respective infectious etiologies, clinical presentations, mechanisms of disease
      development, courses of illness, and treatment options. Future directions related
      to immunoneuropsychiatry are also discussed.

PMID- 22393306
TI  - U12-type spliceosomal introns of Insecta.
AB  - Most of eukaryotic genes are interrupted by introns that need to be removed from
      pre-mRNAs before they can perform their function. This is done by complex
      machinery called spliceosome. Many eukaryotes possess two separate spliceosomal
      systems that process separate sets of introns. The major (U2) spliceosome removes
      majority of introns, while minute fraction of intron repertoire is processed by
      the minor (U12) spliceosome. These two populations of introns are called U2-type
      and U12-type, respectively. The latter fall into two subtypes based on the
      terminal dinucleotides. The minor spliceosomal system has been lost independently
      in some lineages, while in some others few U12-type introns persist. We
      investigated twenty insect genomes in order to better understand the evolutionary
      dynamics of U12-type introns. Our work confirms dramatic drop of U12-type introns
      in Diptera, leaving these genomes just with a handful cases. This is mostly the
      result of intron deletion, but in a number of dipteral cases, minor type introns
      were switched to a major type, as well. Insect genes that harbor U12-type introns
      belong to several functional categories among which proteins binding ions and
      nucleic acids are enriched and these few categories are also overrepresented
      among these genes that preserved minor type introns in Diptera.

PMID- 22393307
TI  - Comparison of protein expression profiles of different stages of lymph nodes
      metastasis in breast cancer.
AB  - Breast cancer is the most common cancer among women worldwide. Breast cancer
      metastasis primarily happens through lymphatic system, where the extent of lymph
      node metastasis is the major factor influencing staging, prognosis and
      therapeutic decision of the disease. We aimed to study the protein expression
      changes in different N (regional lymph nodes) stages of breast cancer. Protein
      expression profiles of breast cancerous and adjacent normal tissues were mapped
      by proteomics approach that comprises of two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE) and tandem mass spectrometry (LC-MS/MS) analysis.
      Calreticulin and tropomyosin alpha 3 chains were the common up-regulated proteins
      in N0, N1 and N2 stages of breast cancer. Potential biomarker for each N stage
      was HSP 70 for N0, 80 k protein H precursor and PDI for N1 stage while 78 kDa
      glucose-regulated protein was found useful for N2 stage. In addition, significant
      up-regulation of PDI A3 was detected only in the metastasized breast cancer. The
      up-regulation expression of these proteins in cancerous tissues can potentially
      use as indicators for diagnosis, treatment and prognosis of different N stages of
      breast cancer.

PMID- 22393308
TI  - Protective effects of garlic oil on hepatocarcinoma induced by N
      nitrosodiethylamine in rats.
AB  - To investigate the protective effects and the possible mechanisms of garlic oil
      (GO) against N-nitrosodiethylamine (NDEA)-induced hepatocarcinoma in rats, Wistar
      rats were gavaged with GO (20 or 40 mg/kg) for 1 week, and then were gavaged with
      GO and NDEA (10 mg/kg) for the next 20 weeks. The changes of morphology,
      histology, the biochemical indices of serum, and DNA oxidative damage of liver
      were examined to assess the protective effects. Lipid peroxidation (LPO),
      antioxidant defense system, and apoptosis-related proteins were measured to
      investigate potential mechanisms. At the end of the study (21 weeks), GO
      administration significantly inhibited the increase of the nodule incidence and
      average nodule number per nodule-bearing liver induced by NDEA, improved
      hepatocellular architecture, and dramatically inhibited NDEA-induced elevation of
      serum biochemical indices (alanine aminotransferase , aspartate aminotransferase,
      alkaline phosphatase and gamma-glutamyl transpeptidase) and hepatic 8-hydroxy-2'
      deoxyguanosine (8-OHdG) levels in a dose-dependent manner. The mechanistic
      studies demonstrated that GO counteracted NDEA-induced oxidative stress in rats
      illustrated by the restoration of glutathione (GSH), superoxide dismutase (SOD),
      catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx),
      glutathione-S-transferase (GST) levels, and the reduction of the malondialdehyde
      (MDA) levels in liver. Furthermore, the mRNA and protein levels of Bcl-2, Bcl-xl,
      andbeta-arrestin-2 were significantly decreased whereas those of Bax and caspase
      3 were significantly increased. These data suggest that GO exhibited significant
      protection against NDEA-induced hepatocarcinogenesis, which might be related with
      the enhancement of the antioxidant activity and the induction of apoptosis.

PMID- 22393309
TI  - Polymorphic allele of human MRC1 confer protection against tuberculosis in a
      Chinese population.
AB  - Mannose receptor is a member of the C-type lectin receptor family involved in
      pathogen molecular-pattern recognition, and plays a critical role in shaping host
      immune response. Single nucleotide polymorphisms (SNPs) in the MRC1 gene may
      affect expression levels and differences in the structure and function of
      proteins in different individuals, thereby affecting individual susceptibility to
      pulmonary tuberculosis. However, to date, MRC1 polymorphisms associated with
      susceptibility to pulmonary tuberculosis have not yet been reported. The present
      study aimed to investigate potential associations of SNPs in the MRC1 gene with
      pulmonary tuberculosis in a Chinese population. Six SNPs (G1186A, G1195A, T1212C,
      C1221G, C1303T and C1323T) in exon 7 of the MRC1 gene were genotyped using the
      PCR and DNA sequencing methods in the pulmonary tuberculosis patients and the
      healthy controls. Linkage disequilibrium analysis was performed between
      polymorphic sites. The study found that the allele frequency of G1186A
      (rs34039386) of the MRC1 gene in a Chinese population was higher in the pulmonary
      tuberculosis group than the healthy control group. There was a significant
      difference in frequency distribution between the two groups (P = 0.037; OR =
      0.76; 95% CI, 0.58-0.98). Genotypic analysis also indicated that the AG genotypes
      in a Chinese population were significantly correlated with pulmonary tuberculosis
      (P < 0.01; OR = 0.57; 95% CI, 0.37-0.87). After adjustment for age and gender,
      G1186A sites were found to be dominant (P < 0.01; OR = 0.59; 95% CI, 0.40-0.87),
      over-dominant (P = 0.045; OR = 0.69; 95% CI, 0.47-0.99) and additive models (P =
      0.041; OR = 0.76; 95% CI, 0.59-0.99) in association with pulmonary tuberculosis.
      But, no association was found between the other 5 SNPs (G1195A, T1212C, C1221G,
      C1303T and C1323T) and tuberculosis (P > 0.05). This study is the first to report
      that genetic variants in the MRC1 gene can be associated with pulmonary
      tuberculosis in a Chinese population, and may reduce the risk of infecting
      pulmonary tuberculosis. This also provides a new experimental basis to clarify
      the pathogenesis of pulmonary tuberculosis.

PMID- 22393310
TI  - Interleukin-11 promotes the progress of gastric carcinoma via abnormally
      expressed versican.
AB  - Versican, a ubiquitous component of the extracellular matrix (ECM), accumulates
      both in tumor stroma and cancer cells and is highly regulated by various
      cytokines. The aberrant expression of versican and its isoforms is known to
      modulate cell proliferation, differentiation, and migration, all of which are
      features of the invasion and metastasis of cancer; versican is also known to
      favour the homeostasis of the ECM. Interleukin-11 (IL-11) is an important
      cytokine that exhibits a wide variety of biological effects in gastric cancer
      development. Here, we analysed the expression of versican isoforms and found that
      the major isoforms expressed by both gastric carcinoma tissue and gastric cell
      lines were V0 and V1, and V1 was significantly higher in gastric carcinoma
      tissue. The treatment of the gastric cell lines AGS and MKN45 with rhIL-11
      resulted in a significant increase in the expression of V0 and V1. Exogenous IL
      11 increased migration in AGS and MKN45 cells, whereas these effects were
      reversed when the expression of V0 and V1 were abolished by siRNA targeting
      versican V0/V1. Collectively, these findings suggest that the abnormally
      expressed versican and its isoforms participate, at least in part, in the
      progress of gastric carcinoma triggered by IL-11.

PMID- 22393311
TI  - Swainsonine activates mitochondria-mediated apoptotic pathway in human lung
      cancer A549 cells and retards the growth of lung cancer xenografts.
AB  - Swainsonine (1, 2, 8-trihyroxyindolizidine, SW), a natural alkaloid, has been
      reported to exhibit anti-cancer activity on several mouse models of human cancer
      and human cancers in vivo. However, the mechanisms of SW-mediated tumor
      regression are not clear. In this study, we investigated the effects of SW on
      several human lung cancer cell lines in vitro. The results showed that SW
      significantly inhibited these cells growth through induction of apoptosis in
      different extent in vitro. Further studies showed that SW treatment up-regulated
      Bax, down-regulated Bcl-2 expression, promoted Bax translocation to mitochondria,
      activated mitochondria-mediated apoptotic pathway, which in turn caused the
      release of cytochrome c, the activation of caspase-9 and caspase-3, and the
      cleavage of poly (ADP-ribose) polymerase (PARP), resulting in A549 cell
      apoptosis. However, the expression of Fas, Fas ligand (FasL) or caspase-8
      activity did not appear significant changes in the process of SW-induced
      apoptosis. Moreover, SW treatment inhibited Bcl-2 expression, promoted Bax
      translocation, cytochrome c release and caspase-3 activity in xenograft tumor
      cells, resulting in a significant decrease of tumor volume and tumor weight in
      the SW-treated xenograft mice groups in comparison to the control group. Taken
      together, this study demonstrated for the first time that SW inhibited A549
      cancer cells growth through a mitochondria-mediated, caspase-dependent apoptotic
      pathway in vitro and in vivo.

PMID- 22393313
TI  - Probing Access Resistance of Solid-state Nanopores with a Scanning Probe
      Microscope Tip.
AB  - An apparatus that integrates solid-state nanopore ionic current measurement with
      a Scanning Probe Microscope has been developed. When a micrometer-scale scanning
      probe tip is near a voltage biased nanometer-scale pore (10-100 nm), the tip
      partially blocks the flow of ions to the pore and increases the pore access
      resistance. The apparatus records the current blockage caused by the probe tip
      and the location of the tip simultaneously. By measuring the current blockage map
      near a nanopore as a function of the tip position in 3D space in salt solution,
      we estimate the relative pore resistance increase due to the tip, DeltaR/R(0), as
      a function of the tip location, nanopore geometry, and salt concentration. The
      amplitude of DeltaR/R(0) also depends on the ratio of the pore length to its
      radius as Ohm's law predicts. When the tip is very close to the pore surface, ~10
      nm, our experiments show that DeltaR/R(0) depends on salt concentration as
      predicted by the Poisson and Nernst-Planck equations. Furthermore, our
      measurements show that DeltaR/R(0) goes to zero when the tip is about five times
      the pore diameter away from the center of the pore entrance. The results in this
      work not only demonstrate a way to probe the access resistance of nanopores
      experimentally, they also provide a way to locate the nanopore in salt solution,
      and open the door to future nanopore experiments for detecting single
      biomolecules attached to a probe tip.

PMID- 22393312
TI  - Association of a functional variant in the Wnt co-receptor LRP6 with early onset
      ileal Crohn's disease.
AB  - Ileal Crohn's Disease (CD), a chronic small intestinal inflammatory disorder, is
      characterized by reduced levels of the antimicrobial peptides DEFA5 (HD-5) and
      DEFA6 (HD-6). Both of these alpha-defensins are exclusively produced in Paneth
      cells (PCs) at small intestinal crypt bases. Different ileal CD-associated genes
      including NOD2, ATG16L1, and recently the beta-catenin-dependant Wnt
      transcription factor TCF7L2 have been linked to impaired PC antimicrobial
      function. The Wnt pathway influences gut mucosal homeostasis and PC maturation,
      besides directly controlling HD-5/6 gene expression. The herein reported
      candidate gene study focuses on another crucial Wnt factor, the co-receptor low
      density lipoprotein receptor-related protein 6 (LRP6). We analysed exonic single
      nucleotide polymorphisms (SNPs) in a large cohort (Oxford: n = 1,893) and
      prospectively tested 2 additional European sample sets (Leuven: n = 688, Vienna:
      n = 1,628). We revealed an association of a non-synonymous SNP (rs2302685;
      Ile1062Val) with early onset ileal CD (OR 1.8; p = 0.00034; for homozygous
      carriers: OR 4.1; p = 0.00004) and additionally with penetrating ileal CD
      behaviour (OR 1.3; p = 0.00917). In contrast, it was not linked to adult onset
      ileal CD, colonic CD, or ulcerative colitis. Since the rare variant is known to
      impair LRP6 activity, we investigated its role in patient mucosa. Overall, LRP6
      mRNA was diminished in patients independently from the genotype. Analysing the
      mRNA levels of PC product in biopsies from genotyped individuals (15 controls, 32
      ileal, and 12 exclusively colonic CD), we found particularly low defensin levels
      in ileal CD patients who were carrying the variant. In addition, we confirmed a
      direct relationship between LRP6 activity and the transcriptional expression of
      HD-5 using transient transfection. Taken together, we identified LRP6 as a new
      candidate gene in ileal CD. Impairments in Wnt signalling and Paneth cell biology
      seem to represent pathophysiological hallmarks in small intestinal inflammation
      and should therefore be considered as interesting targets for new therapeutic
      approaches.

PMID- 22393314
TI  - Differences in zinc status and the leptin axis in anorexic and recovered
      adolescents and young adults: a pilot study.
AB  - BACKGROUND: Evidence from animal studies suggests that leptin metabolism is
      associated with zinc (Zn) status. However, research investigating this
      relationship in adolescents and young adults with anorexia nervosa (AN) is
      scarce; the present study aims to fill that gap. METHODS: Serum concentrations of
      leptin, the soluble leptin receptor (sOB-R) and the free leptin index (FLI) were
      obtained in healthy control subjects (n=19), acutely ill individuals (n=14) and
      recovered patients with AN (n=15). Serum Zn concentrations noted in previous
      research data were also incorporated for all groups. RESULTS: Leptin, FLI and Zn
      concentrations were higher in recovered subjects with AN when compared with
      acutely ill AN patients. Remitted patients showed higher sOB-R concentrations but
      no difference in FLI compared with the control group. Leptin and FLI were lower
      in the acutely ill patients compared with the control subjects, who showed no
      differences in Zn concentrations. Zn concentrations were not correlated with
      leptin, sOB-R or FLI concentrations in any of the three investigated subgroups.
      CONCLUSIONS: The present investigation does not entirely support an association
      between Zn, Leptin and FLI concentrations in subjects with AN, possibly due to
      limited statistical power. Further research and replication of the present
      findings related to the interaction between leptin and Zn is warranted. However,
      with respect to serum leptin levels the data of the present investigation
      indicate that acutely ill and remitted patients with AN differ as regards serum
      leptin concentrations and FLI, which is in line with previous research.

PMID- 22393315
TI  - Synaptic lability after experience-dependent plasticity is not mediated by
      calcium-permeable AMPARs.
AB  - Activity- or experience-dependent plasticity has been associated with the
      trafficking of calcium-permeable alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptors (CP-AMPARs) in a number of experimental
      systems. In some cases it has been shown that CP-AMPARs are only transiently
      present and can be removed in an activity-dependent manner. Here we test the
      hypothesis that the presence of CP-AMPARs confers instability onto recently
      potentiated synapses. Previously we have shown that altered sensory input (single
      whisker experience; SWE) strengthens layer 4-2/3 excitatory synapses in mouse
      primary somatosensory cortex, in part by the trafficking of CP-AMPARs. Both in
      vivo and in vitro, this potentiation is labile, and can be depressed by N-Methyl
      D-aspartate receptor (NMDAR)-activation. In the present study, the role of CP
      AMPARs in conferring this synaptic instability after in vivo potentiation was
      evaluated. We develop an assay to depress the strength of individual layer 4-2/3
      excitatory synapses after SWE, using a strontium (Sr(++))-replaced artificial
      cerebrospinal fluid (ACSF) solution (Sr-depression). This method allows
      disambiguation of changes in quantal amplitude (a post-synaptic measure) from
      changes in event frequency (typically a presynaptic phenomenon). Presynaptic
      stimulation paired with post-synaptic depolarization in Sr(++) lead to a rapid
      and significant reduction in EPSC amplitude with no change in event frequency. Sr
      depression at recently potentiated synapses required NMDARs, but could still
      occur when CP-AMPARs were not present. As a further dissociation between the
      presence of CP-AMPARs and Sr-depression, CP-AMPARs could be detected in some
      cells from control, whisker-intact animals, although Sr-depression was never
      observed. Taken together, our findings suggest that CP-AMPARs are neither
      sufficient nor necessary for synaptic depression after in vivo plasticity in
      somatosensory cortex. This article is part of a Special Issue entitled "Calcium
      permeable AMPARs in synaptic plasticity and disease."

PMID- 22393317
TI  - Increased orienting to unexpected action outcomes in schizophrenia.
AB  - Although some recent research has indicated reduced performance monitoring in
      patients with schizophrenia, the literature on this topic shows some remarkable
      inconsistencies. While most studies suggest diminished error signals following
      error responses, some studies reported normal post-error slowing, while others
      reported reduced post-error slowing. Here we review these studies and highlight
      the most important discrepancies. Furthermore, we argue that overall error rates
      are a mostly neglected issue that can at least partly explain these
      discrepancies. It has been reported previously that post-error slowing depends on
      the error rates. Participants or patients that make more errors are likely to
      show decreased post-error slowing. Therefore, when a group of patients is
      compared to a group of controls, it is extremely important to match error rates.
      For this purpose, we developed a procedure where we matched individuals' error
      rates. In a task where subjects had to press a response key corresponding to one
      of four colors we manipulated the difficulty on an individual basis by varying
      the discriminability between the colors. Schizophrenic patients and a group of
      controls were tested with this procedure showing that differences in accuracy
      disappear. Interestingly, we can see that in patients, the color values that were
      needed to reach similar levels of accuracy correlate with the Positive and
      Negative Syndrome Scale (PANSS) scale, with higher PANSS requiring more color.
      Most important, we found that schizophrenic patients have increased rather than
      decreased post-error slowing when the inter-trial interval (ITI) is short. This
      result can be interpreted within the framework of the orienting account, as it
      has been demonstrated previously that schizophrenic patients show increased
      distractibility.

PMID- 22393318
TI  - The unique brain anatomy of meditation practitioners: alterations in cortical
      gyrification.
AB  - Several cortical regions are reported to vary in meditation practitioners.
      However, prior analyses have focused primarily on examining gray matter or
      cortical thickness. Thus, additional effects with respect to other cortical
      features might have remained undetected. Gyrification (the pattern and degree of
      cortical folding) is an important cerebral characteristic related to the geometry
      of the brain's surface. Thus, exploring cortical gyrification in long-term
      meditators may provide additional clues with respect to the underlying anatomical
      correlates of meditation. This study examined cortical gyrification in a large
      sample (n = 100) of meditators and controls, carefully matched for sex and age.
      Cortical gyrification was established by calculating mean curvature across
      thousands of vertices on individual cortical surface models. Pronounced group
      differences indicating larger gyrification in meditators were evident within the
      left precentral gyrus, right fusiform gyrus, right cuneus, as well as left and
      right anterior dorsal insula (the latter representing the global significance
      maximum). Positive correlations between gyrification and the number of meditation
      years were similarly pronounced in the right anterior dorsal insula. Although the
      exact functional implications of larger cortical gyrification remain to be
      established, these findings suggest the insula to be a key structure involved in
      aspects of meditation. For example, variations in insular complexity could affect
      the regulation of well-known distractions in the process of meditation, such as
      daydreaming, mind-wandering, and projections into past or future. Moreover, given
      that meditators are masters in introspection, awareness, and emotional control,
      increased insular gyrification may reflect an integration of autonomic,
      affective, and cognitive processes. Due to the cross-sectional nature of this
      study, further research is necessary to determine the relative contribution of
      nature and nurture to links between cortical gyrification and meditation.

PMID- 22393316
TI  - EF hand-mediated Ca- and cGMP-signaling in photoreceptor synaptic terminals.
AB  - Photoreceptors, the light-sensitive receptor neurons of the retina, receive and
      transmit a plethora of visual informations from the surrounding world.
      Photoreceptors capture light and convert this energy into electrical signals that
      are conveyed to the inner retina. For synaptic communication with the inner
      retina, photoreceptors make large active zones that are marked by synaptic
      ribbons. These unique synapses support continuous vesicle exocytosis that is
      modulated by light-induced, graded changes of membrane potential. Synaptic
      transmission can be adjusted in an activity-dependent manner, and at the synaptic
      ribbons, Ca(2+)- and cGMP-dependent processes appear to play a central role. EF
      hand-containing proteins mediate many of these Ca(2+)- and cGMP-dependent
      functions. Since continuous signaling of photoreceptors appears to be prone to
      malfunction, disturbances of Ca(2+)- and cGMP-mediated signaling in
      photoreceptors can lead to visual defects, retinal degeneration (rd), and even
      blindness. This review summarizes aspects of signal transmission at the
      photoreceptor presynaptic terminals that involve EF-hand-containing Ca(2+)
      binding proteins.

PMID- 22393319
TI  - Grounding the Meanings in Sensorimotor Behavior using Reinforcement Learning.
AB  - The recent outburst of interest in cognitive developmental robotics is fueled by
      the ambition to propose ecologically plausible mechanisms of how, among other
      things, a learning agent/robot could ground linguistic meanings in its
      sensorimotor behavior. Along this stream, we propose a model that allows the
      simulated iCub robot to learn the meanings of actions (point, touch, and push)
      oriented toward objects in robot's peripersonal space. In our experiments, the
      iCub learns to execute motor actions and comment on them. Architecturally, the
      model is composed of three neural-network-based modules that are trained in
      different ways. The first module, a two-layer perceptron, is trained by back
      propagation to attend to the target position in the visual scene, given the low
      level visual information and the feature-based target information. The second
      module, having the form of an actor-critic architecture, is the most
      distinguishing part of our model, and is trained by a continuous version of
      reinforcement learning to execute actions as sequences, based on a linguistic
      command. The third module, an echo-state network, is trained to provide the
      linguistic description of the executed actions. The trained model generalizes
      well in case of novel action-target combinations with randomized initial arm
      positions. It can also promptly adapt its behavior if the action/target suddenly
      changes during motor execution.

PMID- 22393320
TI  - Dominant Lyapunov exponent and approximate entropy in heart rate variability
      during emotional visual elicitation.
AB  - In this work we characterized the non-linear complexity of Heart Rate Variability
      (HRV) in short time series. The complexity of HRV signal was evaluated during
      emotional visual elicitation by using Dominant Lyapunov Exponents (DLEs) and
      Approximate Entropy (ApEn). We adopted a simplified model of emotion derived from
      the Circumplex Model of Affects (CMAs), in which emotional mechanisms are
      conceptualized in two dimensions by the terms of valence and arousal. Following
      CMA model, a set of standardized visual stimuli in terms of arousal and valence
      gathered from the International Affective Picture System (IAPS) was administered
      to a group of 35 healthy volunteers. Experimental session consisted of eight
      sessions alternating neutral images with high arousal content images. Several
      works can be found in the literature showing a chaotic dynamics of HRV during
      rest or relax conditions. The outcomes of this work showed a clear switching
      mechanism between regular and chaotic dynamics when switching from neutral to
      arousal elicitation. Accordingly, the mean ApEn decreased with statistical
      significance during arousal elicitation and the DLE became negative. Results
      showed a clear distinction between the neutral and the arousal elicitation and
      could be profitably exploited to improve the accuracy of emotion recognition
      systems based on HRV time series analysis.

PMID- 22393321
TI  - Autoimmune myasthenia gravis after sternal fracture.
AB  - We report a 54-year-old woman who suffered a commotio cerebri, whiplash injury
      and a chest trauma with sternal fracture due to a high-velocity car accident. Two
      months later, she developed unilateral ptosis and blurred vision, which worsened
      during the day. Multiple diagnoses were suggested, ranging from thoracic outlet
      syndrome towards depression. Symptoms persisted and five years later, the patient
      consulted a neurologist. Laboratory analysis revealed significantly elevated
      levels of antibodies to acetylcholine receptors, and the diagnosis of myasthenia
      gravis was made. Speculatively, the damage of retrosternal thymic remnants due to
      a sternal fracture might have precipitated the condition or exacerbated
      subclinical disease.

PMID- 22393322
TI  - Unusual sensory disturbances revealing posterior spinal artery infarct.
AB  - Spinal cord infarctions are rare, especially at the cervical level and in the
      posterior spinal artery territory. Moreover, this diagnosis is difficult to
      establish as the clinical picture varies. Even if sensory patterns appear as
      cardinal signs, their distribution can be very variable. We report a rare case of
      posterior cervical cord infarction revealed by an unusual pure sensory clinical
      picture.

PMID- 22393323
TI  - Paroxysmal rhinorrhea after medullary infarct.
AB  - Lateral medullary infarction, known as Wallenberg syndrome, can be accompanied by
      sympathetic dysfunction. We report a case of unilateral intermittent rhinorrhea
      that started after an ischemic stroke in the ipsilateral lateral medulla and
      cerebellum. Rhinorrhea might be mediated by dysfunction of the sympathetic
      autonomic system.

PMID- 22393324
TI  - Giant frontal mucocele occurring 32 years after frontal bone fracture: a case
      report.
AB  - Giant mucoceles of the frontal sinus are rare but their recognition is important
      in the differential diagnosis of proptosis and fronto-orbital lesions. The
      authors describe a patient with frontal giant mucocele with intracranial as well
      as orbit and ethmoid sinus involvement. Thirty-two years after a frontal sinus
      fracture, a 51-year-old female presented with headache, and left exophthalmos and
      ophthalmoplegia. Computed tomography and magnetic resonance imaging demonstrated
      a giant frontal sinus mucocele with extension into the left anterior cranial
      fossa. The mucocele was treated with a transcranial and endoscopic transnasal
      approach. The frontal sinus was then cranialized with reconstruction of the
      posterior wall, and finally a wide nasal drainage was performed. The clinical
      symptoms disappeared immediately after surgery.

PMID- 22393327
TI  - Free-energy and illusions: the cornsweet effect.
AB  - In this paper, we review the nature of illusions using the free-energy
      formulation of Bayesian perception. We reiterate the notion that illusory
      percepts are, in fact, Bayes-optimal and represent the most likely explanation
      for ambiguous sensory input. This point is illustrated using perhaps the simplest
      of visual illusions; namely, the Cornsweet effect. By using plausible prior
      beliefs about the spatial gradients of illuminance and reflectance in visual
      scenes, we show that the Cornsweet effect emerges as a natural consequence of
      Bayes-optimal perception. Furthermore, we were able to simulate the appearance of
      secondary illusory percepts (Mach bands) as a function of stimulus contrast. The
      contrast-dependent emergence of the Cornsweet effect and subsequent appearance of
      Mach bands were simulated using a simple but plausible generative model. Because
      our generative model was inverted using a neurobiologically plausible scheme, we
      could use the inversion as a simulation of neuronal processing and implicit
      inference. Finally, we were able to verify the qualitative and quantitative
      predictions of this Bayes-optimal simulation psychophysically, using stimuli
      presented briefly to normal subjects at different contrast levels, in the context
      of a fixed alternative forced choice paradigm.

PMID- 22393326
TI  - Why Word Learning is not Fast.
AB  - Upon fast mapping, children rarely retain new words even over intervals as short
      as 5 min. In this study, we asked whether the memory process of encoding or
      consolidation is the bottleneck to retention. Forty-nine children, mean age 33
      months, were exposed to eight 2- or-3-syllable nonce neighbors of words in their
      existing lexicons. Didactic training consisted of six exposures to each word in
      the context of its referent, an unfamiliar toy. Productions were elicited four
      times: immediately following the examiner's model, and at 1-min-, 5-min-, and
      multiday retention intervals. At the final two intervals, the examiner said the
      first syllable and provided a beat gesture highlighting target word length in
      syllables as a cue following any erred production. The children were highly
      accurate at immediate posttest. Accuracy fell sharply over the 1-min retention
      interval and again after an additional 5 min. Performance then stabilized such
      that the 5-min and multiday posttests yielded comparable performance. Given this
      time course, we conclude that it was not the post-encoding process of
      consolidation but the process of encoding itself that presented the primary
      bottleneck to retention. Patterns of errors and responses to cueing upon error
      suggested that word forms were particularly vulnerable to partial decay during
      the time course of encoding.

PMID- 22393325
TI  - Molecular targets of omega 3 and conjugated linoleic Fatty acids -
      "micromanaging" cellular response.
AB  - Essential fatty acids cannot be synthesized de novo by mammals and need to be
      ingested either with the diet or through the use of supplements/functional foods
      to ameliorate cardiovascular prognosis. This review focus on the molecular
      targets of omega 3 fatty acids and conjugated linoleic acid, as paradigmatic
      molecules that can be exploited both as nutrients and as pharmacological agents,
      especially as related to cardioprotection. In addition, we indicate novel
      molecular targets, namely microRNAs that might contribute to the observed
      biological activities of such essential fatty acids.

PMID- 22393328
TI  - Peatland microbial communities and decomposition processes in the james bay
      lowlands, Canada.
AB  - Northern peatlands are a large repository of atmospheric carbon due to an
      imbalance between primary production by plants and microbial decomposition. The
      James Bay Lowlands (JBL) of northern Ontario are a large peatland-complex but
      remain relatively unstudied. Climate change models predict the region will
      experience warmer and drier conditions, potentially altering plant community
      composition, and shifting the region from a long-term carbon sink to a source. We
      collected a peat core from two geographically separated (ca. 200 km) ombrotrophic
      peatlands (Victor and Kinoje Bogs) and one minerotrophic peatland (Victor Fen)
      located near Victor Bog within the JBL. We characterized (i) archaeal, bacterial,
      and fungal community structure with terminal restriction fragment length
      polymorphism of ribosomal DNA, (ii) estimated microbial activity using community
      level physiological profiling and extracellular enzymes activities, and (iii) the
      aeration and temperature dependence of carbon mineralization at three depths (0
      10, 50-60, and 100-110 cm) from each site. Similar dominant microbial taxa were
      observed at all three peatlands despite differences in nutrient content and
      substrate quality. In contrast, we observed differences in basal respiration,
      enzyme activity, and the magnitude of substrate utilization, which were all
      generally higher at Victor Fen and similar between the two bogs. However, there
      was no preferential mineralization of carbon substrates between the bogs and
      fens. Microbial community composition did not correlate with measures of
      microbial activity but pH was a strong predictor of activity across all sites and
      depths. Increased peat temperature and aeration stimulated CO(2) production but
      this did not correlate with a change in enzyme activities. Potential microbial
      activity in the JBL appears to be influenced by the quality of the peat substrate
      and the presence of microbial inhibitors, which suggests the existing peat
      substrate will have a large influence on future JBL carbon dynamics.

PMID- 22393329
TI  - Classical labeling of bacterial pathogens according to their lifestyle in the
      host: inconsistencies and alternatives.
AB  - An ample understanding of the complex interactions between host and pathogen will
      improve our ability to develop new prophylactic and therapeutic measures against
      infection. Precise classification of infectious agents in regards to their
      infective lifestyles in the host and corresponding pathogenic implications are
      required because clear concepts are essential to plan fruitful research.
      Classically, pathogenic bacteria are classified as extracellular, facultative
      intracellular, and obligate intracellular. In my opinion, this classification is
      inadequate because, as concluded from data here discussed, it is based on
      inconsistencies and hyper-valorizes the capacity of the infectious agent
      replicate in vitro in cell-free media. For a microbial pathogen, what matters is
      whether intra- or extracellularity is in the context of the in vivo life and in
      association with pathogenicity. When living as a pathogen in association with its
      host, what is relevant in microbiological terms is not the ability to grow in
      artificial cell-free bacteriological media or in environmental niches but whether
      the intracellular infectious agent, besides the phase of intracellular growth
      which is behind its label, also is able to live extracellularly in the natural
      settings of the extracellular territories of their hosts. To eliminate the
      inconsistencies associated with the classical labeling of bacterial pathogens, I
      propose that bacterial pathogens be labeled exclusive extracellular, dual
      intracellular/extracellular and exclusive intracellular based on their infective
      lifestyle in the host, not in the ability to grow in artificial bacteriological
      media.

PMID- 22393331
TI  - Naive Bayesian Classifier and Genetic Risk Score for Genetic Risk Prediction of a
      Categorical Trait: Not so Different after all!
AB  - One of the most popular modeling approaches to genetic risk prediction is to use
      a summary of risk alleles in the form of an unweighted or a weighted genetic risk
      score, with weights that relate to the odds for the phenotype in carriers of the
      individual alleles. Recent contributions have proposed the use of Bayesian
      classification rules using Naive Bayes classifiers. We examine the relation
      between the two approaches for genetic risk prediction and show that the methods
      are mathematically related. In addition, we study the properties of the two
      approaches and describe how they can be generalized to include various models of
      inheritance.

PMID- 22393330
TI  - Chemosensitization as a means to augment commercial antifungal agents.
AB  - Antimycotic chemosensitization and its mode of action are of growing interest.
      Currently, use of antifungal agents in agriculture and medicine has a number of
      obstacles. Foremost of these is development of resistance or cross-resistance to
      one or more antifungal agents. The generally high expense and negative impact, or
      side effects, associated with antifungal agents are two further issues of
      concern. Collectively, these problems are exacerbated by efforts to control
      resistant strains, which can evolve into a treadmill of higher dosages for longer
      periods. This cycle in turn, inflates cost of treatment, dramatically. A further
      problem is stagnation in development of new and effective antifungal agents,
      especially for treatment of human mycoses. Efforts to overcome some of these
      issues have involved using combinations of available antimycotics (e.g.,
      combination therapy for invasive mycoses). However, this approach has had
      inconsistent success and is often associated with a marked increase in negative
      side effects. Chemosensitization by natural compounds to increase effectiveness
      of commercial antimycotics is a somewhat new approach to dealing with the
      aforementioned problems. The potential for safe natural products to improve
      antifungal activity has been observed for over three decades. Chemosensitizing
      agents possess antifungal activity, but at insufficient levels to serve as
      antimycotics, alone. Their main function is to disrupt fungal stress response,
      destabilize the structural integrity of cellular and vacuolar membranes or
      stimulate production of reactive oxygen species, augmenting oxidative stress and
      apoptosis. Use of safe chemosensitizing agents has potential benefit to both
      agriculture and medicine. When co-applied with a commercial antifungal agent, an
      additive or synergistic interaction may occur, augmenting antifungal efficacy.
      This augmentation, in turn, lowers effective dosages, costs, negative side
      effects and, in some cases, countermands resistance.

PMID- 22393333
TI  - Xanthogranulomatous inflammation of the female genital tract: report of three
      cases.
AB  - PURPOSE AND METHODS: This is a series of three cases diagnosed with
      xanthogranulomatous inflammation of the female genital with emphasis on the
      etiology, clinical-pathologic features and biological behavior. Clinical,
      pathologic, radiologic and follow up data are reported. RESULTS: The three cases
      of Xanthogranulomatous inflammation of the female genital tract are the
      followings: 1) one case affecting the endometrium, 2) one case affecting the
      fallopian tube, and 3) one case confined to the ovary. The patient's age was 37,
      22 and 62 year-old, respectively. Histologic examination revealed extensive
      infiltration of foamy histiocytes admixed with variable amount of inflammatory
      cells. The later include plasma cells, lymphocytes, and occasional multinucleated
      giant cells. Immunohistochemistry showed positive staining for CD68, a
      histiocytic marker, in foamy histiocytes, CD3, a T cell marker, and CD20, a B
      cell marker, in the background lymphocytes. The plasma cells were polyclonal with
      expression of both kappa and lambda light chains. CONCLUSION: Xanthogranulomatous
      inflammation of the female genital tract is an unusual lesion, and clinically
      forms mass- like lesion in the pelvic cavity that invades the surrounding
      tissues, which may mimic the tumor clinically and by imaging.

PMID- 22393334
TI  - Additively enhanced antiproliferative effect of interferon combined with
      proanthocyanidin on bladder cancer cells.
AB  - Although interferon (IFN) has been often used as immunotherapy for bladder
      cancer, its efficacy is rather unsatisfactory, demanding further improvement.
      Combination therapy is one of viable options, and grape seed proanthocyanidin
      (GSP) could be such an agent to be used with IFN because it has been shown to
      have anticancer activity. We thus investigated whether combination of IFN and GSP
      might enhance the overall antiproliferative effect on bladder cancer cells in
      vitro. Human bladder cancer T24 cells were employed and treated with the varying
      concentrations of recombinant IFN-alpha(2b) (0-100,000 IU/ml), GSP (0-100
      MUg/ml), or their combinations. IFN-alpha(2b) alone led to a ~50% growth
      reduction at 20,000 (20K) IU/ml, which further declined to ~67% at >=50K IU/ml.
      Similarly, GSP alone induced a ~35% and ~100% growth reduction at 25 and >=50
      MUg/ml, respectively. When IFN-alpha(2b) and GSP were then combined, combination
      of 50K IU/ml IFN-alpha(2b) and 25 MUg/ml GSP resulted in a drastic >95% growth
      reduction. Cell cycle analysis indicated that such an enhanced growth inhibition
      was accompanied by a G(1) cell cycle arrest. This was further confirmed by
      Western blot analysis revealing that expressions of G(1)-specific cell cycle
      regulators (CDK2, CDK4, cyclin E and p27/Kip1) were distinctly modulated with
      such IFN-alpha(2b)/GSP treatment. Therefore, these findings support the notion
      that combination of IFN-alpha(2b) and GSP is capable of additively enhancing
      antiproliferative effect on T24 cells with a G(1) cell cycle arrest, implying an
      adjuvant therapeutic modality for superficial bladder cancer.

PMID- 22393332
TI  - Immune-mediated attenuation of HIV-1.
AB  - Immune escape mutations selected by human leukocyte antigen class I-restricted
      CD8(+) cytotoxic T lymphocytes (CTLs) can result in biologically and clinically
      relevant costs to HIV-1 replicative fitness. This phenomenon may be exploited to
      design an HIV-1 vaccine capable of stimulating effective CTL responses against
      highly conserved, mutationally constrained viral regions, where immune escape
      could occur only at substantial functional costs. Such a vaccine might 'channel'
      HIV-1 evolution towards a less-fit state, thus lowering viral load set points,
      attenuating the infection course and potentially reducing the risk of
      transmission. A major barrier to this approach, however, is the accumulation of
      immune escape variants at the population level, possibly leading to the loss of
      immunogenic CTL epitopes and diminished vaccine-induced cellular immune responses
      as the epidemic progresses. Here, we review the evidence supporting CTL-driven
      replicative defects in HIV-1 and consider the implications of this work for CTL
      based vaccines designed to attenuate the infection course.

PMID- 22393335
TI  - All cancers age-adjusted mortality rate surpasses diseases of the heart.

PMID- 22393336
TI  - Occurrence of chicken parvovirus infection in poland.
AB  - The aim of the foregoing study was the determination of the occurrence of
      parvovirus in chicken flocks from different regions of Poland during 2002-2011.
      The material used for this study originated from chickens showing clinical
      symptoms of stunting and emaciation. For the quick detection of genetic material
      of the viruses in field samples, real-time PCR was applied. The conducted study
      implied on the occurrence of parvoviral infections in Poland in approximately 18%
      of investigated chicken flocks. However, their exact role remains still unknown.

PMID- 22393337
TI  - Exacerbations of chronic obstructive pulmonary disease.
AB  - Epidemiologic data indicate that chronic obstructive pulmonary disease (COPD) is
      a leading cause of morbidity and mortality. Patients with poorly managed COPD are
      likely to experience exacerbations that require emergency department visits or
      hospitalization-two important drivers contributing to escalating healthcare
      resource use and costs associated with the disease. Exacerbations also contribute
      to worsening lung function and negative outcomes in COPD. The aim of this review
      is to present the perspective of nurse practitioners and physician assistants in
      terms of providing the pharmacologic and non-pharmacologic modalities needed to
      treat current and prevent future exacerbations. Major respiratory guidelines
      recommend treatment of acute exacerbations with short-acting bronchodilators,
      oral corticosteroids and antibiotics, as appropriate. Supplementary oxygen and/or
      ventilatory support may also be beneficial to selected patients. Treatments to
      minimize the risk of future exacerbations should include maintenance
      pharmacotherapies, risk-reduction measures (e.g. smoking cessation, influenza and
      pneumonia vaccinations), pulmonary rehabilitation, self-management support and
      follow-up care.

PMID- 22393338
TI  - Short-term effects of high-frequency chest compression and positive expiratory
      pressure in patients with cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis patients require daily airway clearance therapies.
      The primary objective of this study was to compare the short-term efficacy of
      high-frequency chest compression and positive expiratory pressure mask on
      expectorated sputum, pulmonary function, and oxygen saturation in patients with
      CF hospitalized for an acute pulmonary exacerbation. METHODS: A controlled
      randomized cross-over trial with 24 hours between treatments was used. Thirty
      four CF patients (26 +/- 6.5 years) were included in the study. Before and 30
      minutes after each treatment were recorded: pulmonary function testing, oxygen
      saturation, and perceived dyspnea. Preference for the two devices was assessed.
      RESULTS: No statistically significant difference between high-frequency chest
      compression and positive expiratory pressure mask was found in sputum production
      and in lung function testing. A reduction in SpO(2) was found after positive
      expiratory pressure mask (98 +/- 1.0% versus 97 +/- 1.2%; P < 0.001). Both
      treatments induced a statistically significant increase in Borg scale for dyspnea
      without differences between them. Patients reported greater satisfaction with
      positive expiratory pressure mask than with high-frequency chest compression (P <
      0.001). CONCLUSION: High-frequency chest compression and positive expiratory
      pressure mask have comparable short-term effects on expectorated sputum and lung
      function. Although positive expiratory pressure mask was associated with a lower
      SpO(2), it was better tolerated than high-frequency chest compression. KEYWORDS:
      Airway clearance therapies; High-frequency chest compression; Sputum; Cystic
      fibrosis.

PMID- 22393339
TI  - Assessment of Primitive Reflexes in High-risk Newborns.
AB  - BACKGROUND: Assessment of primitive reflexes is one of the earliest, simplest,
      and most frequently used assessment tools among health care providers for
      newborns and young infants. However, very few data exist for high-risk infants in
      this topic. Among the various primitive reflexes, this study was undertaken
      particularly to describe the sucking, Babinski and Moro reflexes in high-risk
      newborns and to explore their relationships with clinical variables. METHODS:
      This study is a cross-sectional descriptive study. Sixty seven high-risk newborns
      including full-term infants required intensive care as well as premature infants
      were recruited in a neonatal intensive care unit using convenient sampling
      method. The sucking, Babinski and Moro reflexes were assessed and classified by
      normal, abnormal and absence. To explore their relationships with clinical
      variables, birth-related variables, brain sonogram results, and behavioral state
      (the Anderson Behavioral State Scale, ABSS) and mental status (the Infant Coma
      Scale, ICS) were assessed. RESULTS: The sucking reflex presented a normal
      response most frequently (63.5%), followed by Babinski reflex (58.7%) and Moro
      reflex (42.9%). Newborns who presented normal sucking and Babinski reflex
      responses were more likely to have older gestational age, heavier birth and
      current weight, higher Apgar scores, shorter length of hospitalization, better
      respiratory conditions, and better mental status assessed by ICS, but not with
      Moro reflex. CONCLUSIONS: High risk newborns presented more frequent abnormal and
      absence responses of primitive reflex and the proportions of the responses varied
      by reflex. Further researches are necessary in exploring diverse aspects of
      primitive reflexes and revealing their clinical implication in the high-risk
      newborns that are unique and different to normal healthy newborns. KEYWORDS:
      Primitive reflex; High risk infants; Korean; Moro reflex; Sucking reflex;
      Babinski reflex; The Anderson Behavioral State Scale; Infant Coma Scale.

PMID- 22393340
TI  - Evaluation of immune responses to seasonal influenza vaccination in healthy
      volunteers in South Apulia, Italy: a pilot study.
AB  - BACKGROUND: The aim of our pilot study is to investigate different components of
      the immune response to influenza vaccination in a group of healthy volunteers. We
      evaluated the cellular immune response (CD4(+) T lymphocytes) by flow cytometry.
      The humoral immune response was assessed by measuring the serum haemagglutination
      inhibition antibody response. METHODS: Healthy adult donors (n = 18), were
      vaccinated with a commercially influenza virus vaccine (FLUARIX(r)
      GlaxoSmithKline S.p.a. Verona, Italy), peripheral blood was drawn the same day as
      influenza virus vaccination and one month later in order to enumerate the antigen
      specific CD4(+) T lymphocytes. Hemagglutination inhibition assay was performed to
      enumerate the titer of neutralizing antibodies. Samples of nasal-pharyngeal
      secretions were taken by swabbing, from ILI (Influenza like Illness) subjects
      among the studied group, in order to verify influenza infections and eventually
      identify viruses using Real Time PCR. RESULTS AND CONCLUSIONS: Parenteral
      influenza vaccination results in significant increase in the CD4(+) Th cell
      population after vaccination. The number of pre-vaccination CD4(+) T cells was
      0.018 [the results are presented as number of percent fluorescent cells per 10
      000 lymphocytes (fixed cells)], while there was a significantly higher number of
      CD4(+) Th cells one month after vaccination (statistical significance was set at
      the level of alpha = 0.01). Twenty-two percent of patients demonstrated
      protective antibody levels to influenza A H1/N1 serotype. None was diagnosed with
      influenza type A or B. KEYWORDS: T cells; Flow cytometry; Influenza virus;
      Influenza vaccine.

PMID- 22393341
TI  - The Importance of H-FABP in Determining the Severity of Carbon Monoxide
      Poisoning.
AB  - BACKGROUND: In this study, we aimed to investigate the importance of the use of
      heart-type fatty acid binding protein (H-FABP) in evaluating the myocardial
      damage in patients admitted to the emergency department with moderate to severe
      carbon monoxide (CO) poisoning. METHODS: All patients admitted to the emergency
      department with severe acute CO intoxication were enrolled the study. The H-FABP
      and cardiac biomarker levels were assessed at 0, 6th and 24th hours. The patients
      were divided into groups as those with normal echocardiography findings and with
      wall motion abnormalities. The differences between the groups for these
      parameters were compared. RESULTS: The mean age of 80 patients was 32.3 +/- 12.9
      years old. 42 of them were male. On admission, 29 (36.3%) had elevated serum
      troponin I levels and 56 (70.0%) had elevated serum H-FABP levels. At 6thhour, 4
      (5.0%) of 80 patients had higher serum H-FABP levels and 23 (28.8%) of them had
      higher serum Troponin I levels than 0 hour. The patients with wall motion
      abnormality had significantly higher serum H-FABP levels compared to the patients
      with normal echocardiography findings at 6th and 24th hours (p = 0.001 and
      0.009). While the serum COHb and H-FABP levels tended to decrease continuously in
      time (p < 0.001), the serum troponin I levels increased at 6th hour and then
      decreased at 24th hour (p = 0.017). CONCLUSION: The serum H-FABP levels are
      useful in identifying the myocardial damage in patients admitted to the emergency
      department with moderate to severe carbon monoxide poisoning at an early phase.
      KEYWORDS: Carbon monoxide; Poisoning; H-FABP; Myocardial injury.

PMID- 22393342
TI  - Self-perceived Difficulties With Suicidal Patients in A Sample of Italian General
      Practitioners.
AB  - BACKGROUND: Suicidal behaviours are relatively common among primary care
      patients, but suicide ideation seems to be poorly detected by GPs. The purpose of
      the present study is to investigate the frequency of issues related to suicidal
      behaviour in GPs' setting and to inquire the level of difficulties perceived by
      physicians when dealing with suicidal patients. METHODS: A survey on 88 GPs in
      Rovigo (Italy) has been conducted through the use of a self-administered
      questionnaire inquiring about suicidal behaviour in patients, personal history
      and outside professional lives. RESULTS: Four out of 5 doctors have encountered
      at least a case of suicide in their professional career, and 3 out of 4 recorded
      at least a case of suicide attempt in a working year. The frequency of personal
      history of suicidal ideation/behaviour was 2.3%. One third of GPs have come into
      contact with suicides or suicide attempts outside the professional setting. Sixty
      one per cent of doctors admitted difficulties in exploring suicidal ideation, but
      tended to ascribe it to a reluctant attitude of patients. CONCLUSIONS: The study
      underscores GPs' need of being helped in the difficult task of recognising
      suicidal patients. KEYWORDS: General practitioner; Suicide ideation; Suicide;
      Suicide attempt.

PMID- 22393343
TI  - Characteristics and Outcome of Patients With Dual Pulmonary Tuberculosis and Non
      mycobacterial Respiratory Infections.
AB  - BACKGROUND: Mixed tuberculosis (TB) and bacterial respiratory infections are
      usually seen in areas where there is an HIV epidemic. However, there have been no
      previous reports regarding TB patients with concomitant bacterial respiratory
      infections in a non-HIV prevalent region. This study was to evaluate the clinical
      characteristics and outcomes of patients with dual TB and bacterial respiratory
      infections in Hualien, Taiwan. METHODS: A retrospective cohort study was
      conducted in a community teaching hospital in Hualien from 2000 to 2007. Those
      who fulfilled the criteria for active pulmonary tuberculosis (PTB) were included
      and divided into subjects with concomitant bacterial infections and controls.
      Their basic data, clinical presentations and in-hospital outcomes were reviewed
      and analyzed. RESULTS: During 2000 - 2007, a total of 182 patients were diagnosed
      as having PTB. Of them, 54 (29.7%) had dual infections. Comorbidities were common
      in these patients. Older age and lower socioeconomic status were present in
      subjects than in controls. In terms of disease characteristics, symptoms of cough
      and sputum production, laboratory findings of leukocytosis with left shift,
      thrombocytopenia, renal insufficiency and lower serum albumin level, as well as
      radiographic patterns of multi-lobar infiltrates and alveolar consolidations
      prevailed amongst subjects (P < 0.05). Delayed diagnosis in PTB and increased
      rates of in-hospital morbidity and mortality associated with polymicrobial
      infections were noted in subjects with dual infections. CONCLUSIONS: In a non-HIV
      prevalent area, patients of older age, lacking access to good health care, and
      suffering from malnutrition were predisposed to dual infections and had poor
      prognosis and outcomes. KEYWORDS: Pulmonary tuberculosis; Dual nontuberculous
      bacterial respiratory infections.

PMID- 22393344
TI  - The Association Between the Uncoupling Protein-1 Gene A-3826G Polymorphism and
      High-density Lipoprotein Cholesterol in A General Japanese Population: A
      Consideration of the Obesity Status.
AB  - BACKGROUND: Limited studies have shown inconsistent data about the association
      between the uncoupling protein 1 (UCP1) gene A-3826G polymorphism and high
      density lipoprotein (HDL) cholesterol levels. The present study investigated the
      association between the A-3826G polymorphism and low HDL-cholesterolemia in non
      obese and obese subjects. METHODS: Anthropometric and biochemical factors, in
      addition to genotyping by an allele-specific DNA assay, were measured in 294
      community-dwelling Japanese subjects (male/female: 127/167, mean age: 65 years).
      Obesity was defined as a body mass index (BMI) >= 25 kg/m(2), and low HDL
      cholesterolemia was defined as < 1.04 mmol/L of HDL-cholesterol. RESULTS: The
      subjects with the G/G genotype (n = 27) showed a significantly higher prevalence
      of low HDL-cholesterolemia (37%) than those with the A/A + A/G genotype (13%) in
      the obese group (n = 102). There was a non-significant difference in the
      prevalence of low HDL-cholesterolemia between subjects with the G/G genotype (n =
      45, 13%) and with the A/A + A/G genotype (15%) in the non-obese group (n = 192).
      A multivariate-adjusted logistic regression analysis of the presence of low HDL
      cholesterolemia revealed that carrying the G/G genotype was an independent and
      significant factor positively associated with low HDL-cholesterolemia [odds ratio
      (OR): 6.85, 95% confidence interval (CI): 1.65-28.49] in the obese group, while
      carrying the G/G genotype exhibited a non-significant but reduced OR, by one
      half, for low HDL-cholesterolemia (OR: 0.51, 95% CI: 0.13-1.96) in the non-obese
      group. CONCLUSIONS: The obesity status could have opposing impacts on the
      relationship between the G/G genotype and low HDL-cholesterolemia, providing
      insight into the need to consider the obesity levels when studying the
      association between the UCP-1 gene A-3826G polymorphism and HDL-cholesterol.
      KEYWORDS: Obesity; Body mass index; HDL-C; Atherosclerotic risk.

PMID- 22393345
TI  - Bilateral brachial plexus home going catheters after digital amputation for
      patient with upper extremity digital gangrene.
AB  - Peripheral nerve catheter placement is used to control surgical pain. Performing
      bilateral brachial plexus block with catheters is not frequently performed; and
      in our case sending patient home with bilateral brachial plexus catheters has not
      been reported up to our knowledge. Our patient is a 57 years old male patient
      presented with bilateral upper extremity digital gangrene on digits 2 through 4
      on both sides with no thumb involvement. The plan was to do the surgery under
      sequential axillary blocks. On the day of surgery a right axillary brachial
      plexus block was performed under ultrasound guidance using 20 ml of 0.75%
      ropivacaine. Patient was taken to the OR and the right fingers amputation was
      carried out under mild sedation without problems. Left axillary brachial plexus
      block was then done as the surgeon was closing the right side, two hours after
      the first block was performed. The left axillary block was done also under
      ultrasound using 20 ml of 2% mepivacaine. The brachial plexus blocks were
      performed in a sequential manner. Surgery was unremarkable, and patient was
      transferred to post anesthetic care unit in stable condition. Over that first
      postoperative night, the patient complained of severe pain at the surgical sites
      with minimal pain relief with parentral opioids. We placed bilateral brachial
      plexus catheters (right axillary and left infra-clavicular brachial plexus
      catheters). Ropivacaine 0.2% infusion was started at 7 ml per hour basal rate
      only with no boluses on each side. The patient was discharged home with the
      catheters in place after receiving the appropriate education. On discharge both
      catheters were connected to a single ON-Q (I-flow Corporation, Lake Forest, CA)
      ball pump with a 750 ml reservoir using a Y connection and were set to deliver a
      fixed rate of 7 ml for each catheter. The brachial plexus catheters were removed
      by the patient on day 5 after surgery without any difficulty. Patient's
      postoperative course was otherwise unremarkable. We concluded that home going
      catheters are very effective in pain control postoperatively and they shorten the
      period of hospital stay. KEYWORDS: Brachial plexus; Home going catheters; Post
      operative pain.

PMID- 22393346
TI  - Mid-diaphyseal Endosteal Thickening With Subsequent Medullary Narrowing in a
      Patient With Hallermann-Streiff Syndrome.
AB  - We report on a 5-year-old girl who presented with the full clinical criteria of
      Hallermann-Streiff syndrome (HSS). Classically, overtubulation (thin and gracile)
      bones are the characteristic and constant features in HSS. Interestingly, our
      present patient manifested unusual mid-diaphyseal endosteal thickening with
      subsequent medullary narrowing (defective endosteal resorption). To the best of
      our knowledge no previous reports described such unusual feature in a patient
      with HSS. KEYWORDS: Hallermann-Streiff syndrome; Mid-diaphyseal thickening;
      Radiology.

PMID- 22393347
TI  - A Difficult Differential Diagnosis of Acute Cholecystitis in a Patient With
      Steroid-induced Diabetes.
AB  - An impairment of gallbladder motility due to autonomic neuropathy may cause
      cholestasis and result in gallbladder stone formation. Diabetes is one of risk
      factors for acute cholecystitis. Diabetes and steroid use are associated with the
      susceptibility to bacterial infections, we are apt to diagnose steroid-induced
      diabetic patients manifesting symptoms of cholecystitis as having acute bacterial
      infective cholecystitis. Here, we report a very rare steroid-induced diabetic
      patient complicated with gallbladder torsion-induced necrotizing cholecystitis
      due to a floating gallbladder. KEYWORDS: Cholecystitis; Diabetes; Floating
      gallbladder; Torsion.

PMID- 22393348
TI  - Polymorphisms in the presumptive promoter region of the SLC2A9 gene are
      associated with gout in a Chinese male population.
AB  - BACKGROUND: Glucose transporter 9 (GLUT9) is a high-capacity/low-affinity urate
      transporter. To date, several recent genome-wide association studies (GWAS) and
      follow-up studies have identified genetic variants of SLC2A9 associated with
      urate concentrations and susceptibility to gout. We therefore investigated
      associations between gout and polymorphisms and haplotypes in the presumptive
      promoter region of GLUT9 in Chinese males. METHODOLOGY/PRINCIPAL FINDINGS: The
      approximately 2000 bp presumptive promoter region upstream of the start site of
      exon 1 of GLUT9 was sequenced and subjected to genetic analysis. A genotype
      phenotype correlation was performed and polymorphisms-induced changes in
      transcription factor binding sites were predicted. Of 21 SNPs identified in
      GLUT9, five had not been previously reported. Two of the SNPs (rs13124007 and
      rs6850166) were associated with susceptibility to gout (p = 0.009 and p = 0.042,
      respectively). The C allele of rs13124007 appeared to be the risk allele for
      predisposition to gout (p = 0.006, OR 1.709 [95% CI 1.162-2.514]). For rs6850166,
      an increased risk of gout was associated with the A allele (p = 0.029, OR 1.645
      [95% CI 1.050-2.577]). After Bonferroni correction, there was statistically
      difference in rs13124007 allele frequencies between gout cases and controls (P =
      0.042). Haplotype analyses showed that haplotype GG was a protective haplotype (p
      = 0.0053) and haplotype CA was associated with increased risk of gout (p =
      0.0326). Genotype-phenotype analysis among gout patients revealed an association
      of rs13124007 with serum triglycerides levels (P = 0.001). The C to G
      substitution in polymorphism rs13124007 resulted in a loss of a binding site for
      transcription factor interferon regulatory factor 1 (IRF-1).
      CONCLUSIONS/SIGNIFICANCE: Polymorphisms rs13124007 and rs6850166 are associated
      with susceptibility to gout in Chinese males.

PMID- 22393349
TI  - Evidence from individual inference for high-dimensional coexistence: long-term
      experiments on recruitment response.
AB  - BACKGROUND: For competing species to coexist, individuals must compete more with
      others of the same species than with those of other species. Ecologists search
      for tradeoffs in how species might partition the environment. The negative
      correlations among competing species that would be indicative of tradeoffs are
      rarely observed. A recent analysis showed that evidence for partitioning the
      environment is available when responses are disaggregated to the individual
      scale, in terms of the covariance structure of responses to environmental
      variation. That study did not relate that variation to the variables to which
      individuals were responding. To understand how this pattern of variation is
      related to niche variables, we analyzed responses to canopy gaps, long viewed as
      a key variable responsible for species coexistence. METHODOLOGY/PRINCIPAL
      FINDINGS: A longitudinal intervention analysis of individual responses to
      experimental canopy gaps with 12 yr of pre-treatment and 8 yr post-treatment
      responses showed that species-level responses are positively correlated--species
      that grow fast on average in the understory also grow fast on average in response
      to gap formation. In other words, there is no tradeoff. However, the joint
      distribution of individual responses to understory and gap showed a negative
      correlation--species having individuals that respond most to gaps when previously
      growing slowly also have individuals that respond least to gaps when previously
      growing rapidly (e.g., Morus rubra), and vice versa (e.g., Quercus prinus).
      CONCLUSIONS/SIGNIFICANCE: Because competition occurs at the individual scale, not
      the species scale, aggregated species-level parameters and correlations hide the
      species-level differences needed for coexistence. By disaggregating models to the
      scale at which the interaction occurs we show that individual variation provides
      insight for species differences.

PMID- 22393350
TI  - Quantitative analysis of the effective functional structure in yeast glycolysis.
AB  - The understanding of the effective functionality that governs the enzymatic self
      organized processes in cellular conditions is a crucial topic in the post-genomic
      era. In recent studies, Transfer Entropy has been proposed as a rigorous, robust
      and self-consistent method for the causal quantification of the functional
      information flow among nonlinear processes. Here, in order to quantify the
      functional connectivity for the glycolytic enzymes in dissipative conditions we
      have analyzed different catalytic patterns using the technique of Transfer
      Entropy. The data were obtained by means of a yeast glycolytic model formed by
      three delay differential equations where the enzymatic rate equations of the
      irreversible stages have been explicitly considered. These enzymatic activity
      functions were previously modeled and tested experimentally by other different
      groups. The results show the emergence of a new kind of dynamical functional
      structure, characterized by changing connectivity flows and a metabolic invariant
      that constrains the activity of the irreversible enzymes. In addition to the
      classical topological structure characterized by the specific location of
      enzymes, substrates, products and feedback-regulatory metabolites, an effective
      functional structure emerges in the modeled glycolytic system, which is dynamical
      and characterized by notable variations of the functional interactions. The
      dynamical structure also exhibits a metabolic invariant which constrains the
      functional attributes of the enzymes. Finally, in accordance with the classical
      biochemical studies, our numerical analysis reveals in a quantitative manner that
      the enzyme phosphofructokinase is the key-core of the metabolic system, behaving
      for all conditions as the main source of the effective causal flows in yeast
      glycolysis.

PMID- 22393351
TI  - Debridement increases survival in a mouse model of subcutaneous anthrax.
AB  - Anthrax is caused by infection with Bacillus anthracis, a spore-forming gram
      positive bacterium. A major virulence factor for B. anthracis is an
      immunomodulatory tripartite exotoxin that has been reported to alter immune cell
      chemotaxis and activation. It has been proposed that B. anthracis infections
      initiate through entry of spores into the regional draining lymph nodes where
      they germinate, grow, and disseminate systemically via the efferent lymphatics.
      If this model holds true, it would be predicted that surgical removal of infected
      tissues, debridement, would have little effect on the systemic dissemination of
      bacteria. This model was tested through the development of a mouse debridement
      model. It was found that removal of the site of subcutaneous infection in the ear
      increased the likelihood of survival and reduced the quantity of spores in the
      draining cervical lymph nodes (cLN). At the time of debridement 12 hours post
      injection measurable levels of exotoxins were present in the ear, cLN, and serum,
      yet leukocytes within the cLN were activated; countering the concept that
      exotoxins inhibit the early inflammatory response to promote bacterial growth. We
      conclude that the initial entry of spores into the draining lymph node of
      cutaneous infections alone is not sufficient to cause systemic disease and that
      debridement should be considered as an adjunct to antibiotic therapy.

PMID- 22393353
TI  - Biodiversity of indigenous Saccharomyces populations from old wineries of south
      eastern Sicily (Italy): preservation and economic potential.
AB  - In recent years, the preservation of biodiversity has become an important issue.
      Despite much public discussion, however, current practices in the food industry
      seldom take account of its potential economic importance: on the contrary, the
      introduction of industrialized agriculture practices over large areas has often
      resulted in a dramatic reduction in biodiversity.In this paper, we report on the
      remarkable degree of biodiversity in the wine yeast populations naturally present
      in a small area of Sicily (Italy) where traditional (non-industrial) winery
      practices are still in place. Out of more than 900 Saccharomyces yeast isolates
      recovered from late spontaneous fermentations, we detected at least 209 strains.
      Most interestingly, when evaluated at the fermentation and technological level, a
      number of isolates were found to be superior to industrial yeast strains. Out of
      a selected group, isolates from two strains were used for experimental
      fermentations in a winery environment and the quality of the wines produced was
      assessed at the technological, quality and sensory levels. Given that the
      characteristics of the wines produced were found to be industrially appealing,
      the study demonstrated the economic potential of preserving the patrimony of
      Sicilian yeast biodiversity and highlighted the importance of maintaining
      traditional wine making practices.

PMID- 22393352
TI  - Systematic review of economic evaluations of preparedness strategies and
      interventions against influenza pandemics.
AB  - BACKGROUND: Although public health guidelines have implications for resource
      allocation, these issues were not explicitly considered in previous WHO pandemic
      preparedness and response guidance. In order to ensure a thorough and informed
      revision of this guidance following the H1N1 2009 pandemic, a systematic review
      of published and unpublished economic evaluations of preparedness strategies and
      interventions against influenza pandemics was conducted. METHODS: The search was
      performed in September 2011 using 10 electronic databases, 2 internet search
      engines, reference list screening, cited reference searching, and direct
      communication with relevant authors. Full and partial economic evaluations
      considering both costs and outcomes were included. Conversely, reviews,
      editorials, and studies on economic impact or complications were excluded.
      Studies were selected by 2 independent reviewers. RESULTS: 44 studies were
      included. Although most complied with the cost effectiveness guidelines, the
      quality of evidence was limited. However, the data sources used were of higher
      quality in economic evaluations conducted after the 2009 H1N1 pandemic.
      Vaccination and drug regimens were varied. Pharmaceutical plus non-pharmaceutical
      interventions are relatively cost effective in comparison to vaccines and/or
      antivirals alone. Pharmaceutical interventions vary from cost saving to high cost
      effectiveness ratios. According to ceiling thresholds (Gross National Income per
      capita), the reduction of non-essential contacts and the use of pharmaceutical
      prophylaxis plus the closure of schools are amongst the cost effective strategies
      for all countries. However, quarantine for household contacts is not cost
      effective even for low and middle income countries. CONCLUSION: The available
      evidence is generally inconclusive regarding the cost effectiveness of
      preparedness strategies and interventions against influenza pandemics. Studies on
      their effectiveness and cost effectiveness should be readily implemented in
      forthcoming events that also involve the developing world. Guidelines for
      assessing the impact of disease and interventions should be drawn up to
      facilitate these studies.

PMID- 22393354
TI  - Effects of temperature, salinity and fish in structuring the macroinvertebrate
      community in shallow lakes: implications for effects of climate change.
AB  - Climate warming may lead to changes in the trophic structure and diversity of
      shallow lakes as a combined effect of increased temperature and salinity and
      likely increased strength of trophic interactions. We investigated the potential
      effects of temperature, salinity and fish on the plant-associated
      macroinvertebrate community by introducing artificial plants in eight comparable
      shallow brackish lakes located in two climatic regions of contrasting
      temperature: cold-temperate and Mediterranean. In both regions, lakes covered a
      salinity gradient from freshwater to oligohaline waters. We undertook day and
      night-time sampling of macroinvertebrates associated with the artificial plants
      and fish and free-swimming macroinvertebrate predators within artificial plants
      and in pelagic areas. Our results showed marked differences in the trophic
      structure between cold and warm shallow lakes. Plant-associated
      macroinvertebrates and free-swimming macroinvertebrate predators were more
      abundant and the communities richer in species in the cold compared to the warm
      climate, most probably as a result of differences in fish predation pressure.
      Submerged plants in warm brackish lakes did not seem to counteract the effect of
      fish predation on macroinvertebrates to the same extent as in temperate
      freshwater lakes, since small fish were abundant and tended to aggregate within
      the macrophytes. The richness and abundance of most plant-associated
      macroinvertebrate taxa decreased with salinity. Despite the lower densities of
      plant-associated macroinvertebrates in the Mediterranean lakes, periphyton
      biomass was lower than in cold temperate systems, a fact that was mainly
      attributed to grazing and disturbance by fish. Our results suggest that, if the
      current process of warming entails higher chances of shallow lakes becoming
      warmer and more saline, climatic change may result in a decrease in
      macroinvertebrate species richness and abundance in shallow lakes.

PMID- 22393355
TI  - The nitric oxide-cyclic GMP pathway regulates FoxO and alters dopaminergic neuron
      survival in Drosophila.
AB  - Activation of the forkhead box transcription factor FoxO is suggested to be
      involved in dopaminergic (DA) neurodegeneration in a Drosophila model of
      Parkinson's disease (PD), in which a PD gene product LRRK2 activates FoxO through
      phosphorylation. In the current study that combines Drosophila genetics and
      biochemical analysis, we show that cyclic guanosine monophosphate (cGMP)
      dependent kinase II (cGKII) also phosphorylates FoxO at the same residue as
      LRRK2, and Drosophila orthologues of cGKII and LRRK2, DG2/For and dLRRK,
      respectively, enhance the neurotoxic activity of FoxO in an additive manner.
      Biochemical assays using mammalian cGKII and FoxO1 reveal that cGKII enhances the
      transcriptional activity of FoxO1 through phosphorylation of the FoxO1 S319 site
      in the same manner as LRRK2. A Drosophila FoxO mutant resistant to
      phosphorylation by DG2 and dLRRK (dFoxO S259A corresponding to human FoxO1 S319A)
      suppressed the neurotoxicity and improved motor dysfunction caused by co
      expression of FoxO and DG2. Nitric oxide synthase (NOS) and soluble guanylyl
      cyclase (sGC) also increased FoxO's activity, whereas the administration of a NOS
      inhibitor L-NAME suppressed the loss of DA neurons in aged flies co-expressing
      FoxO and DG2. These results strongly suggest that the NO-FoxO axis contributes to
      DA neurodegeneration in LRRK2-linked PD.

PMID- 22393356
TI  - A novel isolator-based system promotes viability of human embryos during
      laboratory processing.
AB  - In vitro fertilisation (IVF) and related technologies are arguably the most
      challenging of all cell culture applications. The starting material is a single
      cell from which one aims to produce an embryo capable of establishing a pregnancy
      eventually leading to a live birth. Laboratory processing during IVF treatment
      requires open manipulations of gametes and embryos, which typically involves
      exposure to ambient conditions. To reduce the risk of cellular stress, we have
      developed a totally enclosed system of interlinked isolator-based workstations
      designed to maintain oocytes and embryos in a physiological environment
      throughout the IVF process. Comparison of clinical and laboratory data before and
      after the introduction of the new system revealed that significantly more embryos
      developed to the blastocyst stage in the enclosed isolator-based system compared
      with conventional open-fronted laminar flow hoods. Moreover, blastocysts produced
      in the isolator-based system contained significantly more cells and their
      development was accelerated. Consistent with this, the introduction of the
      enclosed system was accompanied by a significant increase in the clinical
      pregnancy rate and in the proportion of embryos implanting following transfer to
      the uterus. The data indicate that protection from ambient conditions promotes
      improved development of human embryos. Importantly, we found that it was entirely
      feasible to conduct all IVF-related procedures in the isolator-based
      workstations.

PMID- 22393357
TI  - Investigating the intercellular spreading properties of the foamy virus Gag
      protein.
AB  - Small regions called protein transduction domains (PTDs), identified in cellular
      and viral proteins, have been reported to efficiently cross biological membranes.
      Here we show that the structural Gag protein of the prototypic foamy virus (PFV)
      is apparently able to move from cell to cell and to transport the green
      fluorescent protein (GFP) from few transfected cells to the nuclei of the entire
      monolayer. Deletion studies showed that this property lies within the second
      glycine/arginine (GRII) box in the C-terminus of the protein. We also found that
      uptake and nuclear accumulation of Gag GRII expressed as GFP-fusion protein in
      recipient cells was observed only following methanol fixation, but never in
      living cells or when cells were fixed with glutaraldehyde or treated with
      trichloroacetic acid prior to methanol fixation. Absence of intercellular
      spreading in vivo was further confirmed using a sensitive luciferase activity
      assay based on transactivation of the PFV long terminal repeats. Thus, we
      conclude that intercellular spreading of PFV Gag represents an artificial
      diffusion event occurring during cell fixation, followed by nuclear retention
      mediated by the chromatin-binding sequence within the Gag GRII box. In light of
      these results, we advise caution before defining a peptide as PTD on the basis of
      intercellular spreading observed by fluorescence microscopy.

PMID- 22393358
TI  - Information indices with high discriminative power for graphs.
AB  - In this paper, we evaluate the uniqueness of several information-theoretic
      measures for graphs based on so-called information functionals and compare the
      results with other information indices and non-information-theoretic measures
      such as the well-known Balaban J index. We show that, by employing an information
      functional based on degree-degree associations, the resulting information index
      outperforms the Balaban J index tremendously. These results have been obtained by
      using nearly 12 million exhaustively generated, non-isomorphic and unweighted
      graphs. Also, we obtain deeper insights on these and other topological
      descriptors when exploring their uniqueness by using exhaustively generated sets
      of alkane trees representing connected and acyclic graphs in which the degree of
      a vertex is at most four.

PMID- 22393359
TI  - Continuous versus cyclic progesterone exposure differentially regulates
      hippocampal gene expression and functional profiles.
AB  - This study investigated the impact of chronic exposure to continuous (CoP4)
      versus cyclic progesterone (CyP4) alone or in combination with 17beta-estradiol
      (E2) on gene expression profiles targeting bioenergetics, metabolism and
      inflammation in the adult female rat hippocampus. High-throughput qRT-PCR
      analyses revealed that ovarian hormonal depletion induced by ovariectomy (OVX)
      led to multiple significant gene expression alterations, which were to a great
      extent reversed by co-administration of E2 and CyP4. In contrast, co
      administration of E2 and CoP4 induced a pattern highly resembling OVX.
      Bioinformatics analyses further revealed clear disparities in functional profiles
      associated with E2+CoP4 and E2+CyP4. Genes involved in mitochondrial energy (ATP
      synthase alpha subunit; Atp5a1), redox homeostasis (peroxiredoxin 5; Prdx5),
      insulin signaling (insulin-like growth factor I; Igf1), and cholesterol
      trafficking (liver X receptor alpha subtype; Nr1h3), differed in direction of
      regulation by E2+CoP4 (down-regulation relative to OVX) and E2+CyP4 (up
      regulation relative to OVX). In contrast, genes involved in amyloid metabolism
      (beta-secretase; Bace1) differed only in degree of regulation, as both E2+CoP4
      and E2+CyP4 induced down-regulation at different efficacy. E2+CyP4-induced
      changes could be associated with regulation of progesterone receptor membrane
      component 1(Pgrmc1). In summary, results from this study provide evidence at the
      molecular level that differing regimens of hormone therapy (HT) can induce
      disparate gene expression profiles in brain. From a translational perspective,
      confirmation of these results in a model of natural menopause, would imply that
      the common regimen of continuous combined HT may have adverse consequences
      whereas a cyclic combined regimen, which is more physiological, could be an
      effective strategy to maintain neurological health and function throughout
      menopausal aging.

PMID- 22393360
TI  - PCR-TTGE analysis of 16S rRNA from rainbow trout (Oncorhynchus mykiss) gut
      microbiota reveals host-specific communities of active bacteria.
AB  - This study assessed the relative contributions of host genetics and diet in
      shaping the gut microbiota of rainbow trout. Full sibling fish from four
      unrelated families, each consisting of individuals derived from the mating of one
      male and one female belonging to a breeding program, were fed diets containing
      either vegetable proteins or vegetable oils for two months in comparison to a
      control diet consisting of only fish protein and fish oil. Two parallel
      approaches were applied on the same samples: transcriptionally active bacterial
      populations were examined based on RNA analysis and were compared with bacterial
      populations obtained from DNA analysis. Comparison of temporal temperature
      gradient gel electrophoresis (TTGE) profiles from DNA and RNA showed important
      differences, indicating that active bacterial populations were better described
      by RNA analysis. Results showed that some bacterial groups were significantly
      (P<0.05) associated with specific families, indicating that microbiota
      composition may be influenced by the host. In addition, the effect of diet on
      microbiota composition was dependent on the trout family.

PMID- 22393361
TI  - Three Drosophila Hox complex microRNAs do not have major effects on expression of
      evolutionarily conserved Hox gene targets during embryogenesis.
AB  - The discovery of microRNAs has resulted in a major expansion of the number of
      molecules known to be involved in gene regulation. Elucidating the functions of
      animal microRNAs has posed a significant challenge as their target interactions
      with messenger RNAs do not adhere to simple rules. Of the thousands of known
      animal microRNAs, relatively few microRNA:messenger RNA regulatory interactions
      have been biologically validated in an normal organismal context. Here we present
      evidence that three microRNAs from the Hox complex in Drosophila (miR-10-5p, miR
      10-3p, miR-iab-4-5p) do not have significant effects during embryogenesis on the
      expression of Hox genes that contain high confidence microRNAs target sites in
      the 3' untranslated regions of their messenger RNAs. This is significant, in that
      it suggests that many predicted microRNA-target interactions may not be
      biologically relevant, or that the outcomes of these interactions may be so
      subtle that mutants may only show phenotypes in specific contexts, such as in
      environmental stress conditions, or in combinations with other microRNA
      mutations.

PMID- 22393363
TI  - Path curvature discrimination: dependence on gaze direction and optical flow
      speed.
AB  - Many experimental approaches to the control of steering rely on the tangent point
      (TP) as major source of information. The TP is a good candidate to control self
      motion. It corresponds to a singular and salient point in the subject's visual
      field, and its location depends on the road geometry, the direction of self
      motion relative to the road and the position of the driver on the road. However,
      the particular status of the TP in the optical flow, as a local minimum of flow
      speed, has often been left aside. We therefore assume that the TP is actually an
      optimal location in the dynamic optical array to perceive a change in the
      trajectory curvature. In this study, we evaluated the ability of human observers
      to detect variations in their path curvature from optical flow patterns, as a
      function of their gaze direction in a virtual environment. We simulated
      curvilinear self-motion parallel to a ground plane. Using random-dot optic flow
      stimuli of brief duration and a two-alternative forced-choice adaptive procedure,
      we determined path curvature discrimination thresholds, as a function of gaze
      direction. The discrimination thresholds are minimal for a gaze directed toward a
      local minimum of optical flow speed. A model based on Weber fraction of the
      foveal velocities (DeltaV/V) correctly predicts the relationship between
      experimental thresholds and local flow velocities. This model was also tested for
      an optical flow computation integrating larger circular areas in central vision.
      Averaging the flow over five degrees leads to an even better fit of the model to
      experimental thresholds. We also found that the minimal optical flow speed
      direction corresponds to a maximal sensitivity of the visual system, as predicted
      by our model. The spontaneous gazing strategies observed during driving might
      thus correspond to an optimal selection of relevant information in the optical
      flow field.

PMID- 22393362
TI  - Inhibition of the intrinsic but not the extrinsic apoptosis pathway accelerates
      and drives MYC-driven tumorigenesis towards acute myeloid leukemia.
AB  - Myc plays an important role in tumor development, including acute myeloid
      leukemia (AML). However, MYC is also a powerful inducer of apoptosis, which is
      one of the major failsafe programs to prevent cancer development. To clarify the
      relative importance of the extrinsic (death receptor-mediated) versus the
      intrinsic (mitochondrial) pathway of apoptosis in MYC-driven AML, we coexpressed
      MYC together with anti-apoptotic proteins of relevance for AML; BCL-X(L)/BCL-2
      (inhibiting the intrinsic pathway) or FLIP(L) (inhibiting the extrinsic pathway),
      in hematopoietic stems cells (HSCs). Transplantation of HSCs expressing MYC into
      syngeneic recipient mice resulted in development of AML and T-cell lymphomas
      within 7-9 weeks as expected. Importantly, coexpression of MYC together with BCL
      X(L)/BCL-2 resulted in strongly accelerated kinetics and favored tumor
      development towards aggressive AML. In contrast, coexpression of MYC and FLIP(L)
      did neither accelerate tumorigenesis nor change the ratio of AML versus T-cell
      lymphoma. However, a change in distribution of immature CD4(+)CD8(+) versus
      mature CD4(+) T-cell lymphoma was observed in MYC/FLIP(L) mice, possibly as a
      result of increased survival of the CD4+ population, but this did not
      significantly affect the outcome of the disease. In conclusion, our findings
      provide direct evidence that BCL-X(L) and BCL-2 but not FLIP(L) acts in synergy
      with MYC to drive AML development.

PMID- 22393364
TI  - CRDB: database of chemosensory receptor gene families in vertebrate.
AB  - Chemosensory receptors (CR) are crucial for animals to sense the environmental
      changes and survive on earth. The emergence of whole-genome sequences provides us
      an opportunity to identify the entire CR gene repertoires. To completely gain
      more insight into the evolution of CR genes in vertebrates, we identified the
      nearly all CR genes in 25 vertebrates using homology-based approaches. Among
      these CR gene repertoires, nearly half of them were identified for the first time
      in those previously uncharacterized species, such as the guinea pig, giant panda
      and elephant, etc. Consistent with previous findings, we found that the numbers
      of CR genes vary extensively among different species, suggesting an extreme form
      of 'birth-and-death' evolution. For the purpose of facilitating CR gene analysis,
      we constructed a database with the goals to provide a resource for CR genes
      annotation and a web tool for exploring their evolutionary patterns. Besides a
      search engine for the gene extraction from a specific chromosome region, an easy
      to-use phylogenetic analysis tool was also provided to facilitate online
      phylogeny study of CR genes. Our work can provide a rigorous platform for further
      study on the evolution of CR genes in vertebrates.

PMID- 22393365
TI  - Yeast IME2 functions early in meiosis upstream of cell cycle-regulated SBF and
      MBF targets.
AB  - BACKGROUND: In Saccharomyces cerevisiae, the G1 cyclin/cyclin-dependent kinase
      (CDK) complexes Cln1,-2,-3/Cdk1 promote S phase entry during the mitotic cell
      cycle but do not function during meiosis. It has been proposed that the meiosis
      specific protein kinase Ime2, which is required for normal timing of pre-meiotic
      DNA replication, is equivalent to Cln1,-2/Cdk1. These two CDK complexes directly
      catalyze phosphorylation of the B-type cyclin/CDK inhibitor Sic1 during the cell
      cycle to enable its destruction. As a result, Clb5,-6/Cdk1 become activated and
      facilitate initiation of DNA replication. While Ime2 is required for Sic1
      destruction during meiosis, evidence now suggests that Ime2 does not directly
      catalyze Sic1 phosphorylation to target it for destabilization as Cln1,-2/Cdk1 do
      during the cell cycle. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that Sic1
      is eventually degraded in meiotic cells lacking the IME2 gene (ime2Delta),
      supporting an indirect role of Ime2 in Sic1 destruction. We further examined
      global RNA expression comparing wild type and ime2Delta cells. Analysis of these
      expression data has provided evidence that Ime2 is required early in meiosis for
      normal transcription of many genes that are also periodically expressed during
      late G1 of the cell cycle. CONCLUSIONS/SIGNIFICANCE: Our results place Ime2 at a
      position in the early meiotic pathway that lies upstream of the position occupied
      by Cln1,-2/Cdk1 in the analogous cell cycle pathway. Thus, Ime2 may functionally
      resemble Cln3/Cdk1 in promoting S phase entry, or it could play a role even
      further upstream in the corresponding meiotic cascade.

PMID- 22393367
TI  - iCanPlot: visual exploration of high-throughput omics data using interactive
      Canvas plotting.
AB  - Increasing use of high throughput genomic scale assays requires effective
      visualization and analysis techniques to facilitate data interpretation.
      Moreover, existing tools often require programming skills, which discourages
      bench scientists from examining their own data. We have created iCanPlot, a
      compelling platform for visual data exploration based on the latest technologies.
      Using the recently adopted HTML5 Canvas element, we have developed a highly
      interactive tool to visualize tabular data and identify interesting patterns in
      an intuitive fashion without the need of any specialized computing skills. A
      module for geneset overlap analysis has been implemented on the Google App Engine
      platform: when the user selects a region of interest in the plot, the genes in
      the region are analyzed on the fly. The visualization and analysis are
      amalgamated for a seamless experience. Further, users can easily upload their
      data for analysis--which also makes it simple to share the analysis with
      collaborators. We illustrate the power of iCanPlot by showing an example of how
      it can be used to interpret histone modifications in the context of gene
      expression.

PMID- 22393366
TI  - Transcriptome and network changes in climbers at extreme altitudes.
AB  - Extreme altitude can induce a range of cellular and systemic responses. Although
      it is known that hypoxia underlies the major changes and that the physiological
      responses include hemodynamic changes and erythropoiesis, the molecular
      mechanisms and signaling pathways mediating such changes are largely unknown. To
      obtain a more complete picture of the transcriptional regulatory landscape and
      networks involved in extreme altitude response, we followed four climbers on an
      expedition up Mount Xixiabangma (8,012 m), and collected blood samples at four
      stages during the climb for mRNA and miRNA expression assays. By analyzing
      dynamic changes of gene networks in response to extreme altitudes, we uncovered a
      highly modular network with 7 modules of various functions that changed in
      response to extreme altitudes. The erythrocyte differentiation module is the most
      prominently up-regulated, reflecting increased erythrocyte differentiation from
      hematopoietic stem cells, probably at the expense of differentiation into other
      cell lineages. These changes are accompanied by coordinated down-regulation of
      general translation. Network topology and flow analyses also uncovered regulators
      known to modulate hypoxia responses and erythrocyte development, as well as
      unknown regulators, such as the OCT4 gene, an important regulator in stem cells
      and assumed to only function in stem cells. We predicted computationally and
      validated experimentally that increased OCT4 expression at extreme altitude can
      directly elevate the expression of hemoglobin genes. Our approach established a
      new framework for analyzing the transcriptional regulatory network from a very
      limited number of samples.

PMID- 22393368
TI  - Renal function and morphology in aged Beagle dogs before and after hydrocortisone
      administration.
AB  - Objectives of this study were to evaluate glomerular filtration rate (GFR), renal
      structural changes and proteinuria in aged Beagle dogs before and after
      hydrocortisone (HC) administration. Eleven Beagle dogs >=10 years old were
      treated with either hydrocortisone (HC group, n = 6) or placebo (control group, n
      = 5). Urinary markers, GFR and kidney biopsies were evaluated before (T0), during
      (T16 wks) and after discontinuing HC administration (T24 wks). Results indicate
      that HC administration causes a significant increase in GFR. At all time points
      except T16 wks, proteinuria was higher in the control group than in the HC group,
      and there was no significant difference in urinary markers between groups. At T16
      wks, proteinuria, urinary albumin-to-creatinine (c) ratio, immunoglobulin G/c and
      retinol-binding protein/c were higher compared to baseline in the HC group. At
      T0, rare to mild renal lesions were detected in all HC dogs and rare to moderate
      changes in all control dogs. Glomerulosclerosis progressed in both groups until
      T24 wks. Tubular atrophy was detected in three HC dogs at T16 wks and T24 wks,
      but also in five control dogs throughout the study. At every time point, five HC
      dogs and all control dogs had rare to moderate interstitial inflammation. Rare to
      mild interstitial fibrosis was found in up to three HC dogs at T16 wks and T24
      wks, and severe fibrosis in one HC dog at T24 wks. Up to four control dogs had
      rare to mild fibrosis at all time points. These findings indicate that clinically
      healthy, aged Beagle dogs may have considerable renal lesions and proteinuria,
      which could have implications for experimental or toxicological studies.
      Additional research is needed to elucidate glucocorticoid effects on renal
      structure, but functional changes such as hyperfiltration and proteinuria warrant
      attention to kidney function of canine patients with Cushing's syndrome or
      receiving exogenous glucocorticoids.

PMID- 22393369
TI  - Suppression of FOXM1 sensitizes human cancer cells to cell death induced by DNA
      damage.
AB  - Irradiation and DNA-damaging chemotherapeutic agents are commonly used in
      anticancer treatments. Following DNA damage FOXM1 protein levels are often
      elevated. In this study, we sought to investigate the potential role of FOXM1 in
      programmed cell death induced by DNA-damage. Human cancer cells after FOXM1
      suppression were subjected to doxorubicin or gamma-irradiation treatment. Our
      findings indicate that FOXM1 downregulation by stable or transient knockdown
      using RNAi or by treatment with proteasome inhibitors that target FOXM1 strongly
      sensitized human cancer cells of different origin to DNA-damage-induced
      apoptosis. We showed that FOXM1 suppresses the activation of pro-apoptotic JNK
      and positively regulates anti-apoptotic Bcl-2, suggesting that JNK activation and
      Bcl-2 down-regulation could mediate sensitivity to DNA-damaging agent-induced
      apoptosis after targeting FOXM1. Since FOXM1 is widely expressed in human
      cancers, our data further support the fact that it is a valid target for
      combinatorial anticancer therapy.

PMID- 22393370
TI  - Masking of figure-ground texture and single targets by surround inhibition: a
      computational spiking model.
AB  - A visual stimulus can be made invisible, i.e. masked, by the presentation of a
      second stimulus. In the sensory cortex, neural responses to a masked stimulus are
      suppressed, yet how this suppression comes about is still debated. Inhibitory
      models explain masking by asserting that the mask exerts an inhibitory influence
      on the responses of a neuron evoked by the target. However, other models argue
      that the masking interferes with recurrent or reentrant processing. Using
      computer modeling, we show that surround inhibition evoked by ON and OFF
      responses to the mask suppresses the responses to a briefly presented stimulus in
      forward and backward masking paradigms. Our model results resemble several
      previously described psychophysical and neurophysiological findings in perceptual
      masking experiments and are in line with earlier theoretical descriptions of
      masking. We suggest that precise spatiotemporal influence of surround inhibition
      is relevant for visual detection.

PMID- 22393371
TI  - Reelin is involved in transforming growth factor-beta1-induced cell migration in
      esophageal carcinoma cells.
AB  - Reelin (RELN), which is a glycoprotein secreted by Cajal-Retzius cells of the
      developing cerebral cortex, plays an important role in neuronal migration, but
      its role in cell migration and cancer metastasis is largely unclear. Here, we
      showed that cell motility was significantly increased in KYSE-510 cells by TGF
      beta1 treatment. Moreover, TGF-beta1 decreased RELN mRNA expression and
      overexpression of Reelin at least partly reversed TGF-beta1-induced cell
      migration in KYSE-30 cells. Furthermore, this negative regulation of Reelin
      expression by TGF-beta1 was through Snail, one transcription factor which was
      induced by TGF-beta1 in KYSE-510 cells. RELN promoter activity was reduced in
      parallel with the induction of Snail after TGF-beta1 treatment and Snail
      suppressed both RELN promoter activity and expression through binding to E-box
      sequences in the RELN promoter region in ESCC cells. Knockdown of RELN induced
      cell migration in KYSE-510 cells, together with the increase of mesenchymal
      markers expression. Taken together, Reelin is an essential negative regulator in
      the TGF-beta1-induced cell migration process, and is suppressed by TGF-beta
      pathway at the transcriptional level through Snail regulation. Therefore, the
      correlation of Reelin and TGF-beta pathway was critical in cancer metastasis, and
      Reelin could be one potential anti-metastasis target in future clinical practice.

PMID- 22393372
TI  - The imprinted gene DIO3 is a candidate gene for litter size in pigs.
AB  - Genomic imprinting is an important epigenetic phenomenon, which on the phenotypic
      level can be detected by the difference between the two heterozygote classes of a
      gene. Imprinted genes are important in both the development of the placenta and
      the embryo, and we hypothesized that imprinted genes might be involved in female
      fertility traits. We therefore performed an association study for imprinted genes
      related to female fertility traits in two commercial pig populations. For this
      purpose, 309 SNPs in fifteen evolutionary conserved imprinted regions were
      genotyped on 689 and 1050 pigs from the two pig populations. A single SNP
      association study was used to detect additive, dominant and imprinting effects
      related to four reproduction traits; total number of piglets born, the number of
      piglets born alive, the total weight of the piglets born and the total weight of
      the piglets born alive. Several SNPs showed significant (q-value < 0.10) additive
      and dominant effects and one SNP showed a significant imprinting effect. The SNP
      with a significant imprinting effect is closely linked to DIO3, a gene involved
      in thyroid metabolism. The imprinting effect of this SNP explained approximately
      1.6% of the phenotypic variance, which corresponded to approximately 15.5% of the
      additive genetic variance. In the other population, the imprinting effect of this
      QTL was not significant (q-value > 0.10), but had a similar effect as in the
      first population. The results of this study indicate a possible association
      between the imprinted gene DIO3 and female fertility traits in pigs.

PMID- 22393373
TI  - Genomic diversity in two related plant species with and without sex chromosomes-
      Silene latifolia and S. vulgaris.
AB  - BACKGROUND: Genome size evolution is a complex process influenced by
      polyploidization, satellite DNA accumulation, and expansion of retroelements. How
      this process could be affected by different reproductive strategies is still
      poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed differences in the
      number and distribution of major repetitive DNA elements in two closely related
      species, Silene latifolia and S. vulgaris. Both species are diploid and possess
      the same chromosome number (2n = 24), but differ in their genome size and mode of
      reproduction. The dioecious S. latifolia (1C = 2.70 pg DNA) possesses sex
      chromosomes and its genome is 2.5* larger than that of the gynodioecious S.
      vulgaris (1C = 1.13 pg DNA), which does not possess sex chromosomes. We
      discovered that the genome of S. latifolia is larger mainly due to the expansion
      of Ogre retrotransposons. Surprisingly, the centromeric STAR-C and TR1 tandem
      repeats were found to be more abundant in S. vulgaris, the species with the
      smaller genome. We further examined the distribution of major repetitive
      sequences in related species in the Caryophyllaceae family. The results of FISH
      (fluorescence in situ hybridization) on mitotic chromosomes with the Retand
      element indicate that large rearrangements occurred during the evolution of the
      Caryophyllaceae family. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate that the
      evolution of genome size in the genus Silene is accompanied by the expansion of
      different repetitive elements with specific patterns in the dioecious species
      possessing the sex chromosomes.

PMID- 22393374
TI  - Genome-wide analysis of the emerging infection with Mycobacterium avium
      subspecies paratuberculosis in the Arabian camels (Camelus dromedarius).
AB  - Mycobacterium avium subspecies paratuberculosis (M. ap) is the causative agent of
      paratuberculosis or Johne's disease (JD) in herbivores with potential involvement
      in cases of Crohn's disease in humans. JD is spread worldwide and is economically
      important for both beef and dairy industries. Generally, pathogenic ovine strains
      (M. ap-S) are mainly found in sheep while bovine strains (M. ap-C) infect other
      ruminants (e.g. cattle, goat, deer), as well as sheep. In an effort to
      characterize this emerging infection in dromedary/Arabian camels, we successfully
      cultured M. ap from several samples collected from infected camels suffering from
      chronic, intermittent diarrhea suggestive of JD. Gene-based typing of isolates
      indicated that all isolates belong to sheep lineage of strains of M. ap (M. ap
      S), suggesting a putative transmission from infected sheep herds. Screening sheep
      and goat herds associated with camels identified the circulation of this type in
      sheep but not goats. The current genome-wide analysis recognizes these camel
      isolates as a sub-lineage of the sheep strain with a significant number of single
      nucleotide polymorphisms (SNPs) between sheep and camel isolates (~1000 SNPs).
      Such polymorphism could represent geographical differences among isolates or host
      adaptation of M. ap during camel infection. To our knowledge, this is the first
      attempt to examine the genomic basis of this emerging infection in camels with
      implications on the evolution of this important pathogen. The sequenced genomes
      of M. ap isolates from camels will further assist our efforts to understand JD
      pathogenesis and the dynamic of disease transmission across animal species.

PMID- 22393375
TI  - Interpreting patterns of gene expression: signatures of coregulation, the data
      processing inequality, and triplet motifs.
AB  - Various methods of reconstructing transcriptional regulatory networks infer
      transcriptional regulatory interactions (TRIs) between strongly coexpressed gene
      pairs (as determined from microarray experiments measuring mRNA levels).
      Alternatively, however, the coexpression of two genes might imply that they are
      coregulated by one or more transcription factors (TFs), and do not necessarily
      share a direct regulatory interaction. We explore whether and under what
      circumstances gene pairs with a high degree of coexpression are more likely to
      indicate TRIs, coregulation or both. Here we use established TRIs in combination
      with microarray expression data from both Escherichia coli (a prokaryote) and
      Saccharomyces cerevisiae (a eukaryote) to assess the accuracy of predictions of
      coregulated gene pairs and TRIs from coexpressed gene pairs. We find that
      coexpressed gene pairs are more likely to indicate coregulation than TRIs for
      Saccharomyces cerevisiae, but the incidence of TRIs in highly coexpressed gene
      pairs is higher for Escherichia coli. The data processing inequality (DPI) has
      previously been applied for the inference of TRIs. We consider the case where a
      transcription factor gene is known to regulate two genes (one of which is a
      transcription factor gene) that are known not to regulate one another. According
      to the DPI, the non-interacting gene pairs should have the smallest mutual
      information among all pairs in the triplets. While this is sometimes the case for
      Escherichia coli, we find that it is almost always not the case for Saccharomyces
      cerevisiae. This brings into question the usefulness of the DPI sometimes
      employed to infer TRIs from expression data. Finally, we observe that when a TF
      gene is known to regulate two other genes, it is rarely the case that one
      regulatory interaction is positively correlated and the other interaction is
      negatively correlated. Typically both are either positively or negatively
      correlated.

PMID- 22393376
TI  - Effect of chronic escitalopram versus placebo on personality traits in healthy
      first-degree relatives of patients with depression: a randomized trial.
AB  - INTRODUCTION: The serotonergic neurotransmitter system is closely linked to
      depression and personality traits. It is not known if selective serotonin
      reuptake inhibitors (SSRI) have an effect on neuroticism that is independent of
      their effect on depression. Healthy individuals with a genetic liability for
      depression represent a group of particular interest when investigating if
      intervention with SSRIs affects personality. The present trial is the first to
      test the hypothesis that escitalopram may reduce neuroticism in healthy first
      degree relatives of patients with major depressive disorder (MD). METHODS: The
      trial used a randomized, blinded, placebo-controlled parallel-group design. We
      examined the effect of four weeks escitalopram 10 mg daily versus matching
      placebo on personality in 80 people who had a biological parent or sibling with a
      history of MD. The outcome measure on personality traits was change in self
      reported neuroticism scores on the Revised Neuroticism-Extroversion-Openness
      Personality Inventory (NEO-PI-R) and the Eysenck Personality Inventory (EPQ) from
      entry until end of four weeks of intervention. RESULTS: When compared with
      placebo, escitalopram did not significantly affect self-reported NEO-PI-R and EPQ
      neuroticism and extroversion, EPQ psychoticism, NEO-PI-R openness, or NEO-PI-R
      conscientiousness (p all above 0.05). However, escitalopram increased NEO-PI-R
      agreeableness scores significantly compared with placebo (mean; SD) (2.38; 8.09)
      versus (-1.32; 7.94), p = 0.046), but not following correction for multiplicity.
      A trend was shown for increased conscientiousness (p = 0.07). There was no
      significant effect on subclinical depressive symptoms (p = 0.6). CONCLUSION: In
      healthy first-degree relatives of patients with MD, there is no effect of
      escitalopram on neuroticism, but it is possible that escitalopram may increase
      the personality traits of agreeableness and conscientiousness. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT00386841.

PMID- 22393377
TI  - A comparison of scent marking between a monogamous and promiscuous species of
      peromyscus: pair bonded males do not advertise to novel females.
AB  - Scent marking can provide behavioral and physiological information including
      territory ownership and mate advertisement. It is unknown how mating status and
      pair cohabitation influence marking by males from different social systems. We
      compared the highly territorial and monogamous California mouse (Peromyscus
      californicus) to the less territorial and promiscuous white-footed mouse (P.
      leucopus). Single and mated males of both species were assigned to one of the
      following arenas lined with filter paper: control (unscented arena), male scented
      (previously scent-marked by a male conspecific), or females present (containing
      females in small cages). As expected, the territorial P. californicus scent
      marked and overmarked an unfamiliar male conspecific's scent marks more
      frequently than P. leucopus. Species differences in responses to novel females
      were also found based on mating status. The presence of unfamiliar females failed
      to induce changes in scent marking in pair bonded P. californicus even though
      virgin males increased marking behavior. Pair bonding appears to reduce male
      advertisement for novel females. This is in contrast to P. leucopus males that
      continue to advertise regardless of mating status. Our data suggest that
      communication through scent-marking can diverge significantly between species
      based on mating system and that there are physiological mechanisms that can
      inhibit responsiveness of males to female cues.

PMID- 22393378
TI  - Flapping tail membrane in bats produces potentially important thrust during
      horizontal takeoffs and very slow flight.
AB  - Historically, studies concerning bat flight have focused primarily on the wings.
      By analyzing high-speed video taken on 48 individuals of five species of
      vespertilionid bats, we show that the capacity to flap the tail-membrane
      (uropatagium) in order to generate thrust and lift during takeoffs and minimal
      speed flight (<1 m (s-1)) was largely underestimated. Indeed, bats flapped the
      tail-membrane by extensive dorso-ventral fanning motions covering as much as 135
      degrees of arc consistent with thrust generation by air displacement. The degree
      of dorsal extension of the tail-membrane, and thus the potential amount of thrust
      generated during platform launches, was significantly correlated with body mass
      (P = 0.02). Adduction of the hind limbs during upstrokes collapsed the tail
      membrane thereby reducing its surface area and minimizing negative lift forces.
      Abduction of the hind limbs during the downstroke fully expanded the tail
      membrane as it was swept ventrally. The flapping kinematics of the tail-membrane
      is thus consistent with expectations for an airfoil. Timing offsets between the
      wings and tail-membrane during downstrokes was as much as 50%, suggesting that
      the tail-membrane was providing thrust and perhaps lift when the wings were
      retracting through the upstoke phase of the wing-beat cycle. The extent to which
      the tail-membrane was used during takeoffs differed significantly among four
      vespertilionid species (P = 0.01) and aligned with predictions derived from bat
      ecomorphology. The extensive fanning motion of the tail membrane by
      vespertilionid bats has not been reported for other flying vertebrates.

PMID- 22393379
TI  - Systematic review and meta-analysis of randomized clinical trials in the
      treatment of human brucellosis.
AB  - BACKGROUND: Brucellosis is a persistent health problem in many developing
      countries throughout the world, and the search for simple and effective treatment
      continues to be of great importance. METHODS AND FINDINGS: A search was conducted
      in MEDLINE and in the Cochrane Central Register of Controlled Trials (CENTRAL).
      Clinical trials published from 1985 to present that assess different
      antimicrobial regimens in cases of documented acute uncomplicated human
      brucellosis were included. The primary outcomes were relapse, therapeutic
      failure, combined variable of relapse and therapeutic failure, and adverse effect
      rates. A meta-analysis with a fixed effect model was performed and odds ratio
      with 95% confidence intervals were calculated. A random effect model was used
      when significant heterogeneity between studies was verified. Comparison of
      combined doxycycline and rifampicin with a combination of doxycycline and
      streptomycin favors the latter regimen (OR = 3.17; CI95% = 2.05-4.91). There were
      no significant differences between combined doxycycline-streptomycin and combined
      doxycycline-gentamicin (OR = 1.89; CI95% = 0.81-4.39). Treatment with rifampicin
      and quinolones was similar to combined doxycycline-rifampicin (OR = 1.23; CI95% =
      0.63-2.40). Only one study assessed triple therapy with aminoglycoside
      doxycycline-rifampicin and only included patients with uncomplicated brucellosis.
      Thus this approach cannot be considered the therapy of choice until further
      studies have been performed. Combined doxycycline/co-trimoxazole or doxycycline
      monotherapy could represent a cost-effective alternative in certain patient
      groups, and further studies are needed in the future. CONCLUSIONS: Although the
      preferred treatment in uncomplicated human brucellosis is doxycycline
      aminoglycoside combination, other treatments based on oral regimens or
      monotherapy should not be rejected until they are better studied. Triple therapy
      should not be considered the current treatment of choice.

PMID- 22393380
TI  - Probabilistic inference for nucleosome positioning with MNase-based or sonicated
      short-read data.
AB  - We describe a model-based method, PING, for predicting nucleosome positions in
      MNase-Seq and MNase- or sonicated-ChIP-Seq data. PING compares favorably to NPS
      and TemplateFilter in scalability, accuracy and robustness to low read density.
      To demonstrate that PING predictions from widely available sonicated data can
      have sufficient spatial resolution to be to be useful for biological inference,
      we use Illumina H3K4me1 ChIP-seq data to detect changes in nucleosome positioning
      around transcription factor binding sites due to tamoxifen stimulation, to
      discriminate functional and non-functional transcription factor binding sites
      more effectively than with enrichment profiles, and to confirm that the pioneer
      transcription factor Foxa2 associates with the accessible major groove of
      nucleosomal DNA.

PMID- 22393381
TI  - Prey preference of snow leopard (Panthera uncia) in South Gobi, Mongolia.
AB  - Accurate information about the diet of large carnivores that are elusive and
      inhabit inaccessible terrain, is required to properly design conservation
      strategies. Predation on livestock and retaliatory killing of predators have
      become serious issues throughout the range of the snow leopard. Several feeding
      ecology studies of snow leopards have been conducted using classical approaches.
      These techniques have inherent limitations in their ability to properly identify
      both snow leopard feces and prey taxa. To examine the frequency of livestock prey
      and nearly-threatened argali in the diet of the snow leopard, we employed the
      recently developed DNA-based diet approach to study a snow leopard population
      located in the Tost Mountains, South Gobi, Mongolia. After DNA was extracted from
      the feces, a region of ~100 bp long from mitochondrial 12S rRNA gene was
      amplified, making use of universal primers for vertebrates and a blocking
      oligonucleotide specific to snow leopard DNA. The amplicons were then sequenced
      using a next-generation sequencing platform. We observed a total of five
      different prey items from 81 fecal samples. Siberian ibex predominated the diet
      (in 70.4% of the feces), followed by domestic goat (17.3%) and argali sheep
      (8.6%). The major part of the diet was comprised of large ungulates (in 98.8% of
      the feces) including wild ungulates (79%) and domestic livestock (19.7%). The
      findings of the present study will help to understand the feeding ecology of the
      snow leopard, as well as to address the conservation and management issues
      pertaining to this wild cat.

PMID- 22393382
TI  - In vitro phenotypic, genomic and proteomic characterization of a cytokine
      resistant murine beta-TC3 cell line.
AB  - Type 1 diabetes mellitus (T1DM) is caused by the selective destruction of insulin
      producing beta-cells. This process is mediated by cells of the immune system
      through release of nitric oxide, free radicals and pro-inflammatory cytokines,
      which induce a complex network of intracellular signalling cascades, eventually
      affecting the expression of genes involved in beta-cell survival.The aim of our
      study was to investigate possible mechanisms of resistance to cytokine-induced
      beta-cell death. To this purpose, we created a cytokine-resistant beta-cell line
      (beta-TC3R) by chronically treating the beta-TC3 murine insulinoma cell line with
      IL-1beta + IFN-gamma. beta-TC3R cells exhibited higher proliferation rate and
      resistance to cytokine-mediated cell death in comparison to the parental line.
      Interestingly, they maintained expression of beta-cell specific markers, such as
      PDX1, NKX6.1, GLUT2 and insulin. The analysis of the secretory function showed
      that beta-TC3R cells have impaired glucose-induced c-peptide release, which
      however was only moderately reduced after incubation with KCl and tolbutamide.
      Gene expression analysis showed that beta-TC3R cells were characterized by
      downregulation of IL-1beta and IFN-gamma receptors and upregulation of SOCS3, the
      classical negative regulator of cytokines signaling. Comparative proteomic
      analysis showed specific upregulation of 35 proteins, mainly involved in cell
      death, stress response and folding. Among them, SUMO4, a negative feedback
      regulator in NF-kB and JAK/STAT signaling pathways, resulted hyper-expressed.
      Silencing of SUMO4 was able to restore sensitivity to cytokine-induced cell death
      in beta-TC3R cells, suggesting it may play a key role in acquired cytokine
      resistance by blocking JAK/STAT and NF-kB lethal signaling.In conclusion, our
      study represents the first extensive proteomic characterization of a murine
      cytokine-resistant beta-cell line, which might represent a useful tool for
      studying the mechanisms involved in resistance to cytokine-mediated beta-cell
      death. This knowledge may be of potential benefit for patients with T1DM. In
      particular, SUMO4 could be used as a therapeutical target.

PMID- 22393383
TI  - Point-of-care test for detection of urogenital chlamydia in women shows low
      sensitivity. A performance evaluation study in two clinics in Suriname.
AB  - BACKGROUND: In general, point-of-care (POC) tests for Chlamydia trachomatis (Ct)
      show disappointing test performance, especially disappointing sensitivity
      results. However, one study sponsored by the manufacturer (Diagnostics for the
      Real World) reported over 80% sensitivity with their Chlamydia Rapid Test (CRT).
      We evaluated the performance of this CRT in a non-manufacturer-sponsored trial.
      METHODS: Between July 2009 and February 2010, we included samples from 912 women
      in both high- and low-risk clinics for sexually transmitted infections (STIs) in
      Paramaribo, Suriname. Sensitivity, specificity, positive- and negative predictive
      values (PPV and NPV) for CRT compared to NAAT (Aptima, Gen-Probe) were
      determined. Quantitative Ct load and human cell load were determined in all CRT
      and/or NAAT positive samples. RESULTS: CRT compared to NAAT showed a sensitivity
      and specificity of 41.2% (95% CI, 31.9%-50.9%) and 96.4% (95% CI, 95.0%-97.5%),
      respectively. PPV and NPV were 59.2% (95% CI, 47.5%-70.1%) and 92.9% (95% CI,
      91.0%-94.5%), respectively. Quantitative Ct bacterial load was 73 times higher in
      NAAT-positive/CRT-positive samples compared to NAAT-positive/CRT-negative samples
      (p<0.001). Human cell load did not differ between true-positive and false
      negative CRT results (p = 0.835). Sensitivity of CRT in samples with low Ct load
      was 12.5% (95% CI, 5.2%-24.2%) and in samples with high Ct load 73.5% (95% CI,
      59.9%-84.4%). CONCLUSIONS: The sensitivity of CRT for detecting urogenital Ct in
      this non-manufacturer-sponsored study did not meet the expectations as described
      previously. The CRT missed samples with a low Ct load. Improved POC are needed as
      meaningful diagnostic to reduce the disease burden of Ct.

PMID- 22393384
TI  - The role of alveolar epithelial cells in initiating and shaping pulmonary immune
      responses: communication between innate and adaptive immune systems.
AB  - Macrophages and dendritic cells have been recognized as key players in the
      defense against mycobacterial infection. However, more recently, other cells in
      the lungs such as alveolar epithelial cells (AEC) have been found to play
      important roles in the defense and pathogenesis of infection. In the present
      study we first compared AEC with pulmonary macrophages (PuM) isolated from mice
      in their ability to internalize and control Bacillus Calmette-Guerin (BCG) growth
      and their capacity as APCs. AEC were able to internalize and control bacterial
      growth as well as present antigen to primed T cells. Secondly, we compared both
      cell types in their capacity to secrete cytokines and chemokines upon stimulation
      with various molecules including mycobacterial products. Activated PuM and AEC
      displayed different patterns of secretion. Finally, we analyzed the profile of
      response of AEC to diverse stimuli. AEC responded to both microbial and internal
      stimuli exemplified by TLR ligands and IFNs, respectively. The response included
      synthesis by AEC of several factors, known to have various effects in other
      cells. Interestingly, TNF could stimulate the production of CCL2/MCP-1. Since MCP
      1 plays a role in the recruitment of monocytes and macrophages to sites of
      infection and macrophages are the main producers of TNF, we speculate that both
      cell types can stimulate each other. Also, another cell-cell interaction was
      suggested when IFNs (produced mainly by lymphocytes) were able to induce
      expression of chemokines (IP-10 and RANTES) by AEC involved in the recruitment of
      circulating lymphocytes to areas of injury, inflammation, or viral infection. In
      the current paper we confirm previous data on the capacity of AEC regarding
      internalization of mycobacteria and their role as APC, and extend the knowledge
      of AEC as a multifunctional cell type by assessing the secretion of a broad array
      of factors in response to several different types of stimuli.

PMID- 22393385
TI  - Core site-moiety maps reveal inhibitors and binding mechanisms of orthologous
      proteins by screening compound libraries.
AB  - Members of protein families often share conserved structural subsites for
      interaction with chemically similar moieties despite low sequence identity. We
      propose a core site-moiety map of multiple proteins (called CoreSiMMap) to
      discover inhibitors and mechanisms by profiling subsite-moiety interactions of
      immense screening compounds. The consensus anchor, the subsite-moiety
      interactions with statistical significance, of a CoreSiMMap can be regarded as a
      "hot spot" that represents the conserved binding environments involved in
      biological functions. Here, we derive the CoreSiMMap with six consensus anchors
      and identify six inhibitors (IC(50)<8.0 uM) of shikimate kinases (SKs) of
      Mycobacterium tuberculosis and Helicobacter pylori from the NCI database (236,962
      compounds). Studies of site-directed mutagenesis and analogues reveal that these
      conserved interacting residues and moieties contribute to pocket-moiety
      interaction spots and biological functions. These results reveal that our multi
      target screening strategy and the CoreSiMMap can increase the accuracy of
      screening in the identification of novel inhibitors and subsite-moiety
      environments for elucidating the binding mechanisms of targets.

PMID- 22393386
TI  - Lethal Nipah virus infection induces rapid overexpression of CXCL10.
AB  - Nipah virus (NiV) is a recently emerged zoonotic Paramyxovirus that causes
      regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular
      targets of NiV infection are endothelial cells and neurons. To better understand
      virus-host interaction, we analyzed the transcriptome profile of NiV infection in
      primary human umbilical vein endothelial cells. We further assessed some of the
      obtained results by in vitro and in vivo methods in a hamster model and in brain
      samples from NiV-infected patients. We found that NiV infection strongly induces
      genes involved in interferon response in endothelial cells. Among the top ten
      upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein
      10, IP-10), an important chemoattractant involved in the generation of
      inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which
      develop pathology similar to what is seen in humans, expression of CXCL10 mRNA
      was induced in different organs with kinetics that followed NiV replication.
      Finally, we showed intense staining for CXCL10 in the brain of patients who
      succumbed to lethal NiV infection during the outbreak in Malaysia, confirming
      induction of this chemokine in fatal human infections. This study sheds new light
      on NiV pathogenesis, indicating the role of CXCL10 during the course of infection
      and suggests that this chemokine may serve as a potential new marker for lethal
      NiV encephalitis.

PMID- 22393387
TI  - In vitro study of the effects of Angiostrongylus cantonensis larvae extracts on
      apoptosis and dysfunction in the blood-brain barrier (BBB).
AB  - It has been hypothesized that blood-brain barrier (BBB) dysfunction in
      Angiostrongylus cantonensis infection might be due to the apoptosis of the hosts'
      BBB cells. Here, we evaluated this hypothesis through several methods, all based
      on an in vitro mouse BBB model consisting of primary culture brain microvascular
      endothelial cells (BMECs) and brain astrocytic cells (BACs). In the present
      study, a four-hour percolation and HRP permeability experiment showed that A.
      cantonensis larvae extracts can increase the permeability of the BBB. Apoptosis
      among BMECs and BACs after exposure to larvae extracts was monitored by TUNEL and
      annexin-V-FITC/PI double staining. A. cantonensis larvae extracts were found to
      induce apoptosis in both BMECs and BACs. For this reason, we concluded that the
      induction of apoptosis might participate in the BBB dysfunction observed during
      angiostrongyliasis. Improved fundamental understanding of how A. cantonensis
      induces apoptosis may lead to new approaches to the treatment or prevention of
      this parasitic disease.

PMID- 22393388
TI  - Text mining improves prediction of protein functional sites.
AB  - We present an approach that integrates protein structure analysis and text mining
      for protein functional site prediction, called LEAP-FS (Literature Enhanced
      Automated Prediction of Functional Sites). The structure analysis was carried out
      using Dynamics Perturbation Analysis (DPA), which predicts functional sites at
      control points where interactions greatly perturb protein vibrations. The text
      mining extracts mentions of residues in the literature, and predicts that
      residues mentioned are functionally important. We assessed the significance of
      each of these methods by analyzing their performance in finding known functional
      sites (specifically, small-molecule binding sites and catalytic sites) in about
      100,000 publicly available protein structures. The DPA predictions recapitulated
      many of the functional site annotations and preferentially recovered binding
      sites annotated as biologically relevant vs. those annotated as potentially
      spurious. The text-based predictions were also substantially supported by the
      functional site annotations: compared to other residues, residues mentioned in
      text were roughly six times more likely to be found in a functional site. The
      overlap of predictions with annotations improved when the text-based and
      structure-based methods agreed. Our analysis also yielded new high-quality
      predictions of many functional site residues that were not catalogued in the
      curated data sources we inspected. We conclude that both DPA and text mining
      independently provide valuable high-throughput protein functional site
      predictions, and that integrating the two methods using LEAP-FS further improves
      the quality of these predictions.

PMID- 22393389
TI  - Multimorbidity patterns in primary care: interactions among chronic diseases
      using factor analysis.
AB  - OBJECTIVES: The primary objective of this study was to identify the existence of
      chronic disease multimorbidity patterns in the primary care population,
      describing their clinical components and analysing how these patterns change and
      evolve over time both in women and men. The secondary objective of this study was
      to generate evidence regarding the pathophysiological processes underlying
      multimorbidity and to understand the interactions and synergies among the various
      diseases. METHODS: This observational, retrospective, multicentre study utilised
      information from the electronic medical records of 19 primary care centres from
      2008. To identify multimorbidity patterns, an exploratory factor analysis was
      carried out based on the tetra-choric correlations between the diagnostic
      information of 275,682 patients who were over 14 years of age. The analysis was
      stratified by age group and sex. RESULTS: Multimorbidity was found in all age
      groups, and its prevalence ranged from 13% in the 15 to 44 year age group to 67%
      in those 65 years of age or older. Goodness-of-fit indicators revealed sample
      values between 0.50 and 0.71. We identified five patterns of multimorbidity:
      cardio-metabolic, psychiatric-substance abuse, mechanical-obesity-thyroidal,
      psychogeriatric and depressive. Some of these patterns were found to evolve with
      age, and there were differences between men and women. CONCLUSIONS: Non-random
      associations between chronic diseases result in clinically consistent
      multimorbidity patterns affecting a significant proportion of the population.
      Underlying pathophysiological phenomena were observed upon which action can be
      taken both from a clinical, individual-level perspective and from a public health
      or population-level perspective.

PMID- 22393390
TI  - A genetic variant in the promoter region of miR-106b-25 cluster and risk of HBV
      infection and hepatocellular carcinoma.
AB  - BACKGROUND: MiR-106b-25 cluster, hosted in intron 13 of MCM7, may play integral
      roles in diverse processes including immune response and tumorigenesis. A single
      nucleotide polymorphism (SNP), rs999885, is located in the promoter region of
      MCM7. METHODS: We performed a case-control study including 1300 HBV-positive
      hepatocellular carcinoma (HCC) cases, 1344 HBV persistent carriers and 1344
      subjects with HBV natural clearance to test the association between rs999885 and
      the risk of HBV persistent infection and HCC. We also investigated the genotype
      expression correlation between rs999885 and miR-106b-25 cluster in 25 pairs of
      HCC and adjacent non-tumor liver tissues. RESULTS: Compared with the HBV natural
      clearance subjects carrying rs999885 AA genotype, those with AG/GG genotypes had
      a decreased risk of chronic HBV infection with an adjusted odds ratio (OR) of
      0.79 [95% confidence intervals (CIs) = 0.67-0.93]. However, the AG/GG genotypes
      were significantly associated with an increased HCC risk in HBV persistent
      carriers (adjusted OR = 1.25, 95% CIs = 1.06-1.47). Expression analysis revealed
      that the expression level of miR-106b-25 cluster was significantly higher in
      AG/GG carriers than those in AA carriers in non-tumor liver tissues. CONCLUSIONS:
      These findings indicate that the A to G base change of rs999885 may provide a
      protective effect against chronic HBV infection but an increased risk for HCC in
      HBV persistent carriers by altering the expression of the miR-106b-25 cluster.

PMID- 22393391
TI  - The mucin MUC4 and its membrane partner ErbB2 regulate biological properties of
      human CAPAN-2 pancreatic cancer cells via different signalling pathways.
AB  - The mucin MUC4 and its membrane partner the ErbB2 oncogenic receptor are
      potential interacting partners in human pancreatic tumour development. However,
      the way they function is still largely unknown. In this work, we aimed to
      identify the cellular mechanisms and the intracellular signalling pathways under
      the control of both ErbB2 and MUC4 in a human pancreatic adenocarcinomatous cell
      line. Using co-immunoprecipitation and GST pull-down, we show that MUC4 and ErbB2
      interact in the human pancreatic adenocarcinomatous cell line CAPAN-2 via the EGF
      domains of MUC4. Stable cell clones were generated in which either MUC4 or ErbB2
      were knocked down (KD) by a shRNA approach. Biological properties of these cells
      were then studied in vitro and in vivo. Our results show that ErbB2-KD cells are
      more apoptotic and less proliferative (decreased cyclin D1 and increased p27kip1
      expression) while migration and invasive properties were not altered. MUC4-KD
      clones were less proliferative with decreased cyclin D1 expression, G1 cell cycle
      arrest and altered ErbB2/ErbB3 expression. Their migration properties were
      reduced whereas invasive properties were increased. Importantly, inhibition of
      ErbB2 and MUC4 expression did not impair the same signalling pathways (inhibition
      of MUC4 expression affected the JNK pathway whereas that of ErbB2 altered the
      MAPK pathway). Finally, ErbB2-KD and MUC4-KD cells showed impaired tumour growth
      in vivo. Our results show that ErbB2 and MUC4, which interact physically,
      activate different intracellular signalling pathways to regulate biological
      properties of CAPAN-2 pancreatic cancer cells.

PMID- 22393392
TI  - Genetic background modulates the phenotype of a mouse model of DYT1 dystonia.
AB  - DYT1 dystonia is a debilitating neurological disease characterized by involuntary
      twisting movements. The disease is caused by an in-frame deletion (GAG, "DeltaE")
      mutation in the TOR1A gene that encodes the torsinA protein. Intriguingly, only
      30% of mutation carriers exhibit motor symptoms despite the fact that functional
      brain imaging studies show abnormal brain metabolism in all carriers. Because
      genetic modifiers may be a determinant of this reduced penetrance, we examined
      the genetic contribution of three different inbred strains of mice on the DYT1
      mutation in animals that are homozygous (Tor1a(DeltaE/DeltaE)) or heterozygous
      (Tor1a(DeltaE/+); disease state) for the disease-causing DeltaE mutation. We find
      that the DBA/2J, C57BL/6J, and CD1-ICR contribution of genes significantly alter
      lifespan in Tor1a(DeltaE/DeltaE) mice, which die during the first few days of
      life on the 129S6/SvEvTac (129) background. The C57BL/6J (B6) strain
      significantly decreases life expectancy of Tor1a(DeltaE/DeltaE) animals but, like
      129S6/SvEvTac Tor1a(DeltaE/+) mice, congenic C57BL/6J Tor1a(DeltaE/+) mice do not
      exhibit any motor abnormalities. In contrast, the DBA/2J (D2) strain
      significantly increases life expectancy. This effect was not present in congenic
      DBA/2J Tor1a(DeltaE/DeltaE) mice, indicating that the extended lifespan of F2
      129/D2 mice was due to a combination of homozygous and heterozygous allelic
      effects. Our observations suggest that genetic modifiers may alter the penetrance
      of the DeltaE mutation, and that mapping these modifiers may provide fresh
      insight into the torsinA molecular pathway.

PMID- 22393393
TI  - Development of a bead-based multiplex genotyping method for diagnostic
      characterization of HPV infection.
AB  - The accurate genotyping of human papillomavirus (HPV) is clinically important
      because the oncogenic potential of HPV is dependent on specific genotypes. Here,
      we described the development of a bead-based multiplex HPV genotyping (MPG)
      method which is able to detect 20 types of HPV (15 high-risk HPV types 16, 18,
      31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68 and 5 low-risk HPV types 6,
      11, 40, 55, 70) and evaluated its accuracy with sequencing. A total of 890
      clinical samples were studied. Among these samples, 484 were HPV positive and 406
      were HPV negative by consensus primer (PGMY09/11) directed PCR. The genotyping of
      484 HPV positive samples was carried out by the bead-based MPG method. The
      accuracy was 93.5% (95% CI, 91.0-96.0), 80.1% (95% CI, 72.3-87.9) for single and
      multiple infections, respectively, while a complete type mismatch was observed
      only in one sample. The MPG method indiscriminately detected dysplasia of several
      cytological grades including 71.8% (95% CI, 61.5-82.3) of ASCUS (atypical
      squamous cells of undetermined significance) and more specific for high grade
      lesions. For women with HSIL (high grade squamous intraepithelial lesion) and SCC
      diagnosis, 32 women showed a PPV (positive predictive value) of 77.3% (95% CI,
      64.8-89.8). Among women >40 years of age, 22 women with histological cervical
      cancer lesions showed a PPV of 88% (95% CI, 75.3-100). Of the highest risk HPV
      types including HPV-16, 18 and 31 positive women of the same age groups, 34 women
      with histological cervical cancer lesions showed a PPV of 77.3% (95% CI, 65.0
      89.6). Taken together, the bead-based MPG method could successfully detect high
      grade lesions and high-risk HPV types with a high degree of accuracy in clinical
      samples.

PMID- 22393395
TI  - Systemic corticosteroids and early administration of antiviral agents for
      pneumonia with acute wheezing due to influenza A(H1N1)pdm09 in Japan.
AB  - BACKGROUND: Pneumonia patients with wheezing due to influenza A(H1N1)pdm09 were
      frequently treated with systemic corticosteroids in Japan although systemic
      corticosteroid for critically ill patients with pneumonia caused by influenza
      A(H1N1)pdm09 has been controversial. Applicability of systemic corticosteroid
      treatment needs to be evaluated. METHODS/PRINCIPAL FINDINGS: We retrospectively
      reviewed 89 subjects who were diagnosed with influenza A(H1N1)pdm09 and admitted
      to a national hospital, Tokyo during the pandemic period. The median age of
      subjects (45 males) was 8 years (range, 0-71). All subjects were treated with
      antiviral agents and the median time from symptom onset to initiation of
      antiviral agents was 2 days (range, 0-7). Subjects were classified into four
      groups: upper respiratory tract infection, wheezing illness, pneumonia with
      wheezing, and pneumonia without wheezing. The characteristics of each group was
      evaluated. A history of asthma was found more frequently in the wheezing illness
      (55.6%) and pneumonia with wheezing (43.3%) groups than in the other two groups
      (p = 0.017). Corticosteroid treatment was assessed among subjects with pneumonia.
      Oxygen saturation was lower in subjects receiving corticosteroids (steroid group)
      than in subjects not receiving corticosteroids (no-steroid group) (p<0.001). The
      steroid group required greater oxygen supply than the no-steroid group (p<0.001).
      No significant difference was found by the Kaplan-Meier method between the
      steroid and the no-steroid groups in hours to fever alleviation from the
      initiation of antiviral agents and hospitalization days. In logistic regression
      analysis, wheezing, pneumonia and oxygen saturation were independent factors
      associated with using systemic corticosteroids. CONCLUSION: Patients with
      wheezing and a history of asthma were frequently found in the study subjects.
      Systemic corticosteroids together with early administration of antiviral agents
      to pneumonia with wheezing and possibly without wheezing did not result in
      negative clinical outcomes and may prevent progression to severe pneumonia in
      this study population.

PMID- 22393394
TI  - NLRP3 inflammasome: key mediator of neuroinflammation in murine Japanese
      encephalitis.
AB  - BACKGROUND: Japanese Encephalitis virus (JEV) is a common cause of acute and
      epidemic viral encephalitis. JEV infection is associated with microglial
      activation resulting in the production of pro-inflammatory cytokines including
      Interleukin-1 beta (IL-1beta) and Interleukin-18 (IL-18). The Pattern Recognition
      Receptors (PRRs) and the underlying mechanism by which microglia identify the
      viral particle leading to the production of these cytokines is unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: For our studies, we have used murine model of JEV
      infection as well as BV-2 mouse microglia cell line. In this study, we have
      identified a signalling pathway which leads to the activation of caspase-1 as the
      key enzyme responsible for the maturation of both IL-1beta and IL-18 in NACHT,
      LRR and PYD domains-containing protein-3 (NLRP3) dependent manner. Depletion of
      NLRP3 results in the reduction of caspase-1 activity and subsequent production of
      these cytokines. CONCLUSION/SIGNIFICANCE: Our results identify a mechanism
      mediated by Reactive Oxygen Species (ROS) production and potassium efflux as the
      two danger signals that link JEV infection to caspase-1 activation resulting in
      subsequent IL-1beta and IL-18 maturation.

PMID- 22393396
TI  - Comprehensive primer design for analysis of population genetics in non-sequenced
      organisms.
AB  - Nuclear sequence markers are useful tool for the study of the history of
      populations and adaptation. However, it is not easy to obtain multiple nuclear
      primers for organisms with poor or no genomic sequence information. Here we used
      the genomes of organisms that have been fully sequenced to design comprehensive
      sets of primers to amplify polymorphic genomic fragments of multiple nuclear
      genes in non-sequenced organisms. First, we identified a large number of
      candidate polymorphic regions that were flanked on each side by conserved regions
      in the reference genomes. We then designed primers based on these conserved
      sequences and examined whether the primers could be used to amplify sequences in
      target species, montane brown frog (Rana ornativentris), anole lizard (Anolis
      sagrei), guppy (Poecilia reticulata), and fruit fly (Drosophila melanogaster),
      for population genetic analysis. We successfully obtained polymorphic markers for
      all target species studied. In addition, we found that sequence identities of the
      regions between the primer sites in the reference genomes affected the
      experimental success of DNA amplification and identification of polymorphic loci
      in the target genomes, and that exonic primers had a higher success rate than
      intronic primers in amplifying readable sequences. We conclude that this
      comparative genomic approach is a time- and cost-effective way to obtain
      polymorphic markers for non-sequenced organisms, and that it will contribute to
      the further development of evolutionary ecology and population genetics for non
      sequenced organisms, aiding in the understanding of the genetic basis of
      adaptation.

PMID- 22393397
TI  - Targeted inactivation of Snail family EMT regulatory factors by a Co(III)-Ebox
      conjugate.
AB  - Snail family proteins are core EMT (epithelial-mesenchymal transition) regulatory
      factors that play essential roles in both development and disease processes and
      have been associated with metastasis in carcinomas. Snail factors are required
      for the formation of neural crest stem cells in most vertebrate embryos, as well
      as for the migratory invasive behavior of these cells. Snail factors have
      recently been linked to the formation of cancer stem cells, and expression of
      Snail proteins may be associated with tumor recurrence and resistance to
      chemotherapy and radiotherapy. We report that Co(III)-Ebox is a potent inhibitor
      of Snail-mediated transcriptional repression in breast cancer cells and in the
      neural crest of Xenopus. We further show that the activity of Co(III)-Ebox can be
      modulated by temperature, increasing the utility of this conjugate as a Snail
      inhibitor in model organisms. We exploit this feature to further delineate the
      requirements for Snail function during neural crest development, showing that in
      addition to the roles that Snail factors play in neural crest precursor formation
      and neural crest EMT/migration, inhibition of Snail function after the onset of
      neural crest migration leads to a loss of neural crest derived melanocytes.
      Co(III)-Ebox-mediated inhibition therefore provides a powerful tool for analysing
      the function of these core EMT factors with unparalleled temporal resolution.
      Moreover, the potency of Co(III)-Ebox as a Snail inhibitor in breast cancer cells
      suggests its potential as a therapeutic inhibitor of tumor progression and
      metastasis.

PMID- 22393398
TI  - The emergence of somatotopic maps of the body in S1 in rats: the correspondence
      between functional and anatomical organization.
AB  - Most of what we know about cortical map development and plasticity comes from
      studies in mice and rats, and for the somatosensory cortex, almost exclusively
      from the whisker-dominated posteromedial barrel fields. Whiskers are the main
      effector organs of mice and rats, and their representation in cortex and
      subcortical pathways is a highly derived feature of murine rodents. This
      specialized anatomical organization may therefore not be representative of
      somatosensory cortex in general, especially for species that utilize other body
      parts as their main effector organs, like the hands of primates. For these
      reasons, we examined the emergence of whole body maps in developing rats using
      electrophysiological recording techniques. In P5, P10, P15, P20 and adult rats,
      multiple recordings were made in the medial portion of S1 in each animal.
      Subsequently, these functional maps were related to anatomical parcellations of
      S1 based on a variety of histological stains. We found that at early postnatal
      ages (P5) medial S1 was composed almost exclusively of the representation of the
      vibrissae. At P10, other body part representations including the hindlimb and
      forelimb were present, although these were not topographically organized. By P15,
      a clear topographic organization began to emerge coincident with a reduction in
      receptive field size. By P20, body maps were adult-like. This study is the first
      to describe how topography of the body develops in S1 in any mammal. It indicates
      that anatomical parcellations and functional maps are initially incongruent but
      become tightly coupled by P15. Finally, because anatomical and functional
      specificity of developing barrel cortex appears much earlier in postnatal life
      than the rest of the body, the entire primary somatosensory cortex should be
      considered when studying general topographic map formation in development.

PMID- 22393399
TI  - Myelin 2',3'-cyclic nucleotide 3'-phosphodiesterase: active-site ligand binding
      and molecular conformation.
AB  - The 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) is a highly abundant
      membrane-associated enzyme in the myelin sheath of the vertebrate nervous system.
      CNPase is a member of the 2H phosphoesterase family and catalyzes the formation
      of 2'-nucleotide products from 2',3'-cyclic substrates; however, its
      physiological substrate and function remain unknown. It is likely that CNPase
      participates in RNA metabolism in the myelinating cell. We solved crystal
      structures of the phosphodiesterase domain of mouse CNPase, showing the binding
      mode of nucleotide ligands in the active site. The binding mode of the product 2'
      AMP provides a detailed view of the reaction mechanism. Comparisons of CNPase
      crystal structures highlight flexible loops, which could play roles in substrate
      recognition; large differences in the active-site vicinity are observed when
      comparing more distant members of the 2H family. We also studied the full-length
      CNPase, showing its N-terminal domain is involved in RNA binding and
      dimerization. Our results provide a detailed picture of the CNPase active site
      during its catalytic cycle, and suggest a specific function for the previously
      uncharacterized N-terminal domain.

PMID- 22393400
TI  - Inhibition of endothelial cell proliferation and tumor angiogenesis by up
      regulating NDRG2 expression in breast cancer cells.
AB  - The N-myc downstream-regulated gene 2 (NDRG2) is involved in tumor cell
      differentiation and apoptosis, but its function in tumor angiogenesis remains to
      be established. Here, we employed adenovirus overexpressing NDRG2 (Ad-NDRG2) to
      efficiently up-regulate target gene expression in the NDRG2-low-expressing,
      breast cancer cell line MCF-7. Moreover, VEGF secretion was decreased in MCF-7
      cells infected by Ad-NDRG2, and medium conditioned by these infected cells could
      significantly inhibit the proliferation, tube formation and invasion of human
      umbilical vein endothelial cells (HUVECs). Further study indicated that the
      angiogenesis promoting factors VEGF and HIF-1alpha were down-regulated, whereas
      the angiogenesis suppressing factors p53 and VHL were up-regulated in MCF-7 cells
      infected by Ad-NDRG2. Finally, in a nude mouse model, intratumoral injections of
      Ad-NDRG2 every 3 days for 20 days significantly inhibited the growth and
      angiogenesis of xenografted MCF-7 tumors. In summary, these data indicate that
      NDRG2 may be involved in angiogenesis by impacting the expression of angiogenesis
      related factors. Thus, specific overexpression of NDRG2 by adenovirus represents
      a promising approach for the treatment of tumor angiogenesis.

PMID- 22393402
TI  - Intra-genomic ribosomal RNA polymorphism and morphological variation in Elphidium
      macellum suggests inter-specific hybridization in foraminifera.
AB  - Elphidium macellum is a benthic foraminifer commonly found in the Patagonian
      fjords. To test whether its highly variable morphotypes are ecophenotypes or
      different genotypes, we analysed 70 sequences of the SSU rRNA gene from 25
      specimens. Unexpectedly, we identified 11 distinct ribotypes, with up to 5
      ribotypes co-occurring within the same specimen. The ribotypes differ by varying
      blocks of sequence located at the end of stem-loop motifs in the three expansion
      segments specific to foraminifera. These changes, distinct from typical SNPs and
      indels, directly affect the structure of the expansion segments. Their mosaic
      distribution suggests that ribotypes originated by recombination of two or more
      clusters of ribosomal genes. We propose that this expansion segment polymorphism
      (ESP) could originate from hybridization of morphologically different populations
      of Patagonian Elphidium. We speculate that the complex geological history of
      Patagonia enhanced divergence of coastal foraminiferal species and contributed to
      increasing genetic and morphological variation.

PMID- 22393401
TI  - IL-10 regulates viral lung immunopathology during acute respiratory syncytial
      virus infection in mice.
AB  - Interleukin (IL-) 10 is a pleiotropic cytokine with broad immunosuppressive
      functions, particularly at mucosal sites such as the intestine and lung. Here we
      demonstrate that infection of BALB/c mice with respiratory syncytial virus (RSV)
      induced IL-10 production by CD4(+) and CD8(+) T cells in the airways at later
      time points (e.g. day 8); a proportion of these cells also co-produced IFN-gamma.
      Furthermore, RSV infection of IL-10(-/-) mice resulted in more severe disease
      with enhanced weight loss, delayed recovery and greater cell infiltration of the
      respiratory tract without affecting viral load. In addition, IL-10(-/-) mice had
      a pronounced airway neutrophilia and heightened levels of pro-inflammatory
      cytokines and chemokines in the bronchoalveolar lavage fluid. Notably, the
      proportion of lung T cells producing IFN-gamma was enhanced, suggesting that IL
      10 may act in an autocrine manner to dampen effector T cell responses. Similar
      findings were made in mice treated with anti-IL-10R antibody and infected with
      RSV. Therefore, IL-10 inhibits disease and inflammation in mice infected with
      RSV, especially during recovery from infection.

PMID- 22393403
TI  - Spatial dynamics and expanded vertical niche of blue sharks in oceanographic
      fronts reveal habitat targets for conservation.
AB  - Dramatic population declines among species of pelagic shark as a result of
      overfishing have been reported, with some species now at a fraction of their
      historical biomass. Advanced telemetry techniques enable tracking of spatial
      dynamics and behaviour, providing fundamental information on habitat preferences
      of threatened species to aid conservation. We tracked movements of the highest
      pelagic fisheries by-catch species, the blue shark Prionace glauca, in the North
      east Atlantic using pop-off satellite-linked archival tags to determine the
      degree of space use linked to habitat and to examine vertical niche. Overall,
      blue sharks moved south-west of tagging sites (English Channel; southern
      Portugal), exhibiting pronounced site fidelity correlated with localized
      productive frontal areas, with estimated space-use patterns being significantly
      different from that of random walks. Tracked female sharks displayed behavioural
      variability in diel depth preferences, both within and between individuals. Diel
      depth use ranged from normal DVM (nDVM; dawn descent, dusk ascent), to reverse
      DVM (rDVM; dawn ascent, dusk descent), to behavioural patterns where no diel
      differences were apparent. Results showed that blue sharks occupy some of the
      most productive marine zones for extended periods and structure diel activity
      patterns across multiple spatio-temporal scales in response to particular habitat
      types. In so doing, sharks occupied an extraordinarily broad vertical depth range
      for their size (1.0-2.0 m fork length), from the surface into the bathypelagic
      realm (max. dive depth, 1160 m). The space-use patterns of blue sharks indicated
      they spend much of the time in areas where pelagic longlining activities are
      often highest, and in depth zones where these fisheries particularly target other
      species, which could account for the rapid declines recently reported for blue
      sharks in many parts of the world's oceans. Our results provide habitat targets
      for blue shark conservation that may also be relevant to other pelagic species.

PMID- 22393404
TI  - Characterizing RecA-independent induction of Shiga toxin2-encoding phages by EDTA
      treatment.
AB  - BACKGROUND: The bacteriophage life cycle has an important role in Shiga toxin
      (Stx) expression. The induction of Shiga toxin-encoding phages (Stx phages)
      increases toxin production as a result of replication of the phage genome, and
      phage lysis of the host cell also provides a means of Stx toxin to exit the cell.
      Previous studies suggested that prophage induction might also occur in the
      absence of SOS response, independently of RecA. METHODOLOGY/PRINCIPAL FINDINGS:
      The influence of EDTA on RecA-independent Stx2 phage induction was assessed, in
      laboratory lysogens and in EHEC strains carrying Stx2 phages in their genome, by
      Real-Time PCR. RecA-independent mechanisms described for phage lambda induction
      (RcsA and DsrA) were not involved in Stx2 phage induction. In addition, mutations
      in the pathway for the stress response of the bacterial envelope to EDTA did not
      contribute to Stx2 phage induction. The effect of EDTA on Stx phage induction is
      due to its chelating properties, which was also confirmed by the use of citrate,
      another chelating agent. Our results indicate that EDTA affects Stx2 phage
      induction by disruption of the bacterial outer membrane due to chelation of
      Mg(2+). In all the conditions evaluated, the pH value had a decisive role in Stx2
      phage induction. CONCLUSIONS/SIGNIFICANCE: Chelating agents, such as EDTA and
      citrate, induce Stx phages, which raises concerns due to their frequent use in
      food and pharmaceutical products. This study contributes to our understanding of
      the phenomenon of induction and release of Stx phages as an important factor in
      the pathogenicity of Shiga toxin-producing Escherichia coli (STEC) and in the
      emergence of new pathogenic strains.

PMID- 22393405
TI  - Raman spectroscopy provides a powerful diagnostic tool for accurate determination
      of albumin glycation.
AB  - We present the first demonstration of glycated albumin detection and
      quantification using Raman spectroscopy without the addition of reagents.
      Glycated albumin is an important marker for monitoring the long-term glycemic
      history of diabetics, especially as its concentrations, in contrast to glycated
      hemoglobin levels, are unaffected by changes in erythrocyte life times.
      Clinically, glycated albumin concentrations show a strong correlation with the
      development of serious diabetes complications including nephropathy and
      retinopathy. In this article, we propose and evaluate the efficacy of Raman
      spectroscopy for determination of this important analyte. By utilizing the pre
      concentration obtained through drop-coating deposition, we show that glycation of
      albumin leads to subtle, but consistent, changes in vibrational features, which
      with the help of multivariate classification techniques can be used to
      discriminate glycated albumin from the unglycated variant with 100% accuracy.
      Moreover, we demonstrate that the calibration model developed on the glycated
      albumin spectral dataset shows high predictive power, even at substantially lower
      concentrations than those typically encountered in clinical practice. In fact,
      the limit of detection for glycated albumin measurements is calculated to be
      approximately four times lower than its minimum physiological concentration.
      Importantly, in relation to the existing detection methods for glycated albumin,
      the proposed method is also completely reagent-free, requires barely any sample
      preparation and has the potential for simultaneous determination of glycated
      hemoglobin levels as well. Given these key advantages, we believe that the
      proposed approach can provide a uniquely powerful tool for quantification of
      glycation status of proteins in biopharmaceutical development as well as for
      glycemic marker determination in routine clinical diagnostics in the future.

PMID- 22393406
TI  - Nicotine-like effects of the neonicotinoid insecticides acetamiprid and
      imidacloprid on cerebellar neurons from neonatal rats.
AB  - BACKGROUND: Acetamiprid (ACE) and imidacloprid (IMI) belong to a new, widely used
      class of pesticide, the neonicotinoids. With similar chemical structures to
      nicotine, neonicotinoids also share agonist activity at nicotinic acetylcholine
      receptors (nAChRs). Although their toxicities against insects are well
      established, their precise effects on mammalian nAChRs remain to be elucidated.
      Because of the importance of nAChRs for mammalian brain function, especially
      brain development, detailed investigation of the neonicotinoids is needed to
      protect the health of human children. We aimed to determine the effects of
      neonicotinoids on the nAChRs of developing mammalian neurons and compare their
      effects with nicotine, a neurotoxin of brain development. METHODOLOGY/PRINCIPAL
      FINDINGS: Primary cultures of cerebellar neurons from neonatal rats allow for
      examinations of the developmental neurotoxicity of chemicals because the various
      stages of neurodevelopment-including proliferation, migration, differentiation,
      and morphological and functional maturation-can be observed in vitro. Using these
      cultures, an excitatory Ca(2+)-influx assay was employed as an indicator of
      neural physiological activity. Significant excitatory Ca(2+) influxes were evoked
      by ACE, IMI, and nicotine at concentrations greater than 1 uM in small neurons in
      cerebellar cultures that expressed the mRNA of the alpha3, alpha4, and alpha7
      nAChR subunits. The firing patterns, proportion of excited neurons, and peak
      excitatory Ca(2+) influxes induced by ACE and IMI showed differences from those
      induced by nicotine. However, ACE and IMI had greater effects on mammalian
      neurons than those previously reported in binding assay studies. Furthermore, the
      effects of the neonicotinoids were significantly inhibited by the nAChR
      antagonists mecamylamine, alpha-bungarotoxin, and dihydro-beta-erythroidine.
      CONCLUSIONS/SIGNIFICANCE: This study is the first to show that ACE, IMI, and
      nicotine exert similar excitatory effects on mammalian nAChRs at concentrations
      greater than 1 uM. Therefore, the neonicotinoids may adversely affect human
      health, especially the developing brain.

PMID- 22393407
TI  - Astrocyte-specific expression patterns associated with the PDGF-induced glioma
      microenvironment.
AB  - BACKGROUND: The tumor microenvironment contains normal, non-neoplastic cells that
      may contribute to tumor growth and maintenance. Within PDGF-driven murine
      gliomas, tumor-associated astrocytes (TAAs) are a large component of the tumor
      microenvironment. The function of non-neoplastic astrocytes in the glioma
      microenvironment has not been fully elucidated; moreover, the differences between
      these astrocytes and normal astrocytes are unknown. We therefore sought to
      identify genes and pathways that are increased in TAAs relative to normal
      astrocytes and also to determine whether expression of these genes correlates
      with glioma behavior. METHODOLOGY/PRINCIPAL FINDINGS: We compared the gene
      expression profiles of TAAs to normal astrocytes and found the Antigen
      Presentation Pathway to be significantly increased in TAAs. We then identified a
      gene signature for glioblastoma (GBM) TAAs and validated the expression of some
      of those genes within the tumor. We also show that TAAs are derived from the non
      tumor, stromal environment, in contrast to the Olig2+ tumor cells that constitute
      the neoplastic elements in our model. Finally, we validate this GBM TAA signature
      in patients and show that a TAA-derived gene signature predicts survival
      specifically in the human proneural subtype of glioma. CONCLUSIONS/SIGNIFICANCE:
      Our data identifies unique gene expression patterns between populations of TAAs
      and suggests potential roles for stromal astrocytes within the glioma
      microenvironment. We show that certain stromal astrocytes in the tumor
      microenvironment express a GBM-specific gene signature and that the majority of
      these stromal astrocyte genes can predict survival in the human disease.

PMID- 22393408
TI  - Macro-to-micro structural proteomics: native source proteins for high-throughput
      crystallization.
AB  - Structural biology and structural genomics projects routinely rely on
      recombinantly expressed proteins, but many proteins and complexes are difficult
      to obtain by this approach. We investigated native source proteins for high
      throughput protein crystallography applications. The Escherichia coli proteome
      was fractionated, purified, crystallized, and structurally characterized. Macro
      scale fermentation and fractionation were used to subdivide the soluble proteome
      into 408 unique fractions of which 295 fractions yielded crystals in microfluidic
      crystallization chips. Of the 295 crystals, 152 were selected for optimization,
      diffraction screening, and data collection. Twenty-three structures were
      determined, four of which were novel. This study demonstrates the utility of
      native source proteins for high-throughput crystallography.

PMID- 22393409
TI  - Genetic diversity and population structure of Saccharomyces cerevisiae strains
      isolated from different grape varieties and winemaking regions.
AB  - We herein evaluate intraspecific genetic diversity of fermentative vineyard
      associated S. cerevisiae strains and evaluate relationships between grape
      varieties and geographical location on populational structures. From the musts
      obtained from 288 grape samples, collected from two wine regions (16 vineyards,
      nine grape varieties), 94 spontaneous fermentations were concluded and 2820 yeast
      isolates were obtained that belonged mainly (92%) to the species S. cerevisiae.
      Isolates were classified in 321 strains by the use of ten microsatellite markers.
      A high strain diversity (8-43 strains per fermentation) was associated with high
      percentage (60-100%) of fermenting samples per vineyard, whereas a lower
      percentage of spontaneous fermentations (0-40%) corresponded to a rather low
      strain diversity (1-10 strains per fermentation).For the majority of the
      populations, observed heterozygosity (Ho) was about two to five times lower than
      the expected heterozygosity (He). The inferred ancestry showed a very high degree
      of admixture and divergence was observed between both grape variety and
      geographical region. Analysis of molecular variance showed that 81-93% of the
      total genetic variation existed within populations, while significant
      differentiation within the groups could be detected. Results from AMOVA analysis
      and clustering of allelic frequencies agree in the distinction of genetically
      more dispersed populations from the larger wine region compared to the less
      extended region. Our data show that grape variety is a driver of populational
      structures, because vineyards with distinct varieties harbor genetically more
      differentiated S. cerevisiae populations. Conversely, S. cerevisiae strains from
      vineyards in close proximity (5-10 km) that contain the same grape variety tend
      to be less divergent. Populational similarities did not correlate with the
      distance between vineyards of the two wine regions. Globally, our results show
      that populations of S. cerevisiae in vineyards may occur locally due to multi
      factorial influences, one of them being the grape variety.

PMID- 22393411
TI  - Roles of the amino terminal region and repeat region of the Plasmodium berghei
      circumsporozoite protein in parasite infectivity.
AB  - The circumsporozoite protein (CSP) plays a key role in malaria sporozoite
      infection of both mosquito salivary glands and the vertebrate host. The conserved
      Regions I and II have been well studied but little is known about the immunogenic
      central repeat region and the N-terminal region of the protein. Rodent malaria
      Plasmodium berghei parasites, in which the endogenous CS gene has been replaced
      with the avian Plasmodium gallinaceum CS (PgCS) sequence, develop normally in the
      A. stephensi mosquito midgut but the sporozoites are not infectious. We therefore
      generated P. berghei transgenic parasites carrying the PgCS gene, in which the
      repeat region was replaced with the homologous region of P. berghei CS (PbCS). A
      further line, in which both the N-terminal region and repeat region were replaced
      with the homologous regions of PbCS, was also generated. Introduction of the PbCS
      repeat region alone, into the PgCS gene, did not rescue sporozoite species
      specific infectivity. However, the introduction of both the PbCS repeat region
      and the N-terminal region into the PgCS gene completely rescued infectivity, in
      both the mosquito vector and the mammalian host. Immunofluorescence experiments
      and western blot analysis revealed correct localization and proteolytic
      processing of CSP in the chimeric parasites. The results demonstrate, in vivo,
      that the repeat region of P. berghei CSP, alone, is unable to mediate sporozoite
      infectivity in either the mosquito or the mammalian host, but suggest an
      important role for the N-terminal region in sporozoite host cell invasion.

PMID- 22393410
TI  - Loss and gain of function in SERPINB11: an example of a gene under selection on
      standing variation, with implications for host-pathogen interactions.
AB  - Serine protease inhibitors (SERPINs) are crucial in the regulation of diverse
      biological processes including inflammation and immune response. SERPINB11,
      located in the 18q21 gene cluster, is a polymorphic gene/pseudogene coding for a
      non-inhibitory SERPIN. In a genome-wide scan for recent selection, SERPINB11 was
      identified as a potential candidate gene for adaptive evolution in Yoruba. The
      present study sought a better understanding of the evolutionary history of
      SERPINB11, with special focus on evaluating its selective signature. Through the
      resequencing of coding and noncoding regions of SERPINB11 in 20 Yorubans and
      analyzing primate orthologous sequences, we identified a full-length SERPINB11
      variant encoding a non-inhibitory SERPIN as the putative candidate of selection-
      probably driven to higher frequencies by an adaptive response using preexisting
      variation. In addition, we detected contrasting evolutionary features of
      SERPINB11 in primates: While primate phylogeny as a whole is under purifying
      selection, the human lineage shows evidence of positive selection in a few
      codons, all associated with the active SERPINB11. Comparative modeling studies
      suggest that positively selected codons reduce SERPINB11's ability to undergo the
      conformational changes typical of inhibitory SERPINs--suggesting that it is
      evolving towards a new non-inhibitory function in humans. Significant
      correlations between SERPINB11 variants and the environmental variables,
      pastoralism and pathogen richness, have led us to propose a selective advantage
      through host-pathogen interactions, possibly linked to an adaptive response
      combating the emergence of infectious diseases in recent human evolution. This
      work represents the first description of a resurrected gene in humans, and may
      well exemplify selection on standing variation triggered by drastic ecological
      shifts.

PMID- 22393412
TI  - Pathogenic connexin-31 forms constitutively active hemichannels to promote
      necrotic cell death.
AB  - Mutations in Connexin-31 (Cx31) are associated with multiple human diseases
      including erythrokeratodermia variabilis (EKV). The molecular action of Cx31
      pathogenic mutants remains largely elusive. We report here that expression of EKV
      pathogenic mutant Cx31R42P induces cell death with necrotic characteristics.
      Inhibition of hemichannel activity by a connexin hemichannel inhibitor or high
      extracellular calcium suppresses Cx31R42P-induced cell death. Expression of
      Cx31R42P induces ER stress resulting in reactive oxygen species (ROS) production,
      in turn, to regulate gating of Cx31R42P hemichannels and Cx31R42P induced cell
      death. Moreover, Cx31R42P hemichannels play an important role in mediating ATP
      release from the cell. In contrast, no hemichannel activity was detected with
      cells expressing wildtype Cx31. Together, the results suggest that Cx31R42P forms
      constitutively active hemichannels to promote necrotic cell death. The Cx31R42P
      active hemichannels are likely resulted by an ER stress mediated ROS
      overproduction. The study identifies a mechanism of EKV pathogenesis induced by a
      Cx31 mutant and provides a new avenue for potential treatment strategy of the
      disease.

PMID- 22393414
TI  - Genetic affinities of the central Indian tribal populations.
AB  - BACKGROUND: The central Indian state Madhya Pradesh is often called as 'heart of
      India' and has always been an important region functioning as a trinexus belt for
      three major language families (Indo-European, Dravidian and Austroasiatic). There
      are less detailed genetic studies on the populations inhabited in this region.
      Therefore, this study is an attempt for extensive characterization of genetic
      ancestries of three tribal populations, namely; Bharia, Bhil and Sahariya,
      inhabiting this region using haploid and diploid DNA markers.
      METHODOLOGY/PRINCIPAL FINDINGS: Mitochondrial DNA analysis showed high diversity,
      including some of the older sublineages of M haplogroup and prominent R lineages
      in all the three tribes. Y-chromosomal biallelic markers revealed high frequency
      of Austroasiatic-specific M95-O2a haplogroup in Bharia and Sahariya, M82-H1a in
      Bhil and M17-R1a in Bhil and Sahariya. The results obtained by haploid as well as
      diploid genetic markers revealed strong genetic affinity of Bharia (a Dravidian
      speaking tribe) with the Austroasiatic (Munda) group. The gene flow from
      Austroasiatic group is further confirmed by their Y-STRs haplotype sharing
      analysis, where we determined their founder haplotype from the North Munda
      speaking tribe, while, autosomal analysis was largely in concordant with the
      haploid DNA results. CONCLUSIONS/SIGNIFICANCE: Bhil exhibited largely Indo
      European specific ancestry, while Sahariya and Bharia showed admixed genetic
      package of Indo-European and Austroasiatic populations. Hence, in a landscape
      like India, linguistic label doesn't unequivocally follow the genetic footprints.

PMID- 22393413
TI  - Measuring and estimating GFR and treatment effect in ADPKD patients: results and
      implications of a longitudinal cohort study.
AB  - Trials failed to demonstrate protective effects of investigational treatments on
      glomerular filtration rate (GFR) reduction in Autosomal Dominant Polycystic
      Kidney Disease (ADPKD). To assess whether above findings were explained by
      unreliable GFR estimates, in this academic study we compared GFR values centrally
      measured by iohexol plasma clearance with corresponding values estimated by
      Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) and abbreviated
      Modification of Diet in Renal Disease (aMDRD) formulas in ADPKD patients
      retrieved from four clinical trials run by a Clinical Research Center and five
      Nephrology Units in Italy. Measured baseline GFRs and one-year GFR changes
      averaged 78.6+/-26.7 and 8.4+/-10.3 mL/min/1.73 m(2) in 111 and 71 ADPKD
      patients, respectively. CKD-Epi significantly overestimated and aMDRD
      underestimated baseline GFRs. Less than half estimates deviated by <10% from
      measured values. One-year estimated GFR changes did not detect measured changes.
      Both formulas underestimated GFR changes by 50%. Less than 9% of estimates
      deviated <10% from measured changes. Extent of deviations even exceeded that of
      measured one-year GFR changes. In ADPKD, prediction formulas unreliably estimate
      actual GFR values and fail to detect their changes over time. Direct kidney
      function measurements by appropriate techniques are needed to adequately evaluate
      treatment effects in clinics and research.

PMID- 22393416
TI  - From social network (centralized vs. decentralized) to collective decision-making
      (unshared vs. shared consensus).
AB  - Relationships we have with our friends, family, or colleagues influence our
      personal decisions, as well as decisions we make together with others. As in
      human beings, despotism and egalitarian societies seem to also exist in animals.
      While studies have shown that social networks constrain many phenomena from
      amoebae to primates, we still do not know how consensus emerges from the
      properties of social networks in many biological systems. We created artificial
      social networks that represent the continuum from centralized to decentralized
      organization and used an agent-based model to make predictions about the patterns
      of consensus and collective movements we observed according to the social
      network. These theoretical results showed that different social networks and
      especially contrasted ones--star network vs. equal network--led to totally
      different patterns. Our model showed that, by moving from a centralized network
      to a decentralized one, the central individual seemed to lose its leadership in
      the collective movement's decisions. We, therefore, showed a link between the
      type of social network and the resulting consensus. By comparing our theoretical
      data with data on five groups of primates, we confirmed that this relationship
      between social network and consensus also appears to exist in animal societies.

PMID- 22393415
TI  - Nef alleles from all major HIV-1 clades activate Src-family kinases and enhance
      HIV-1 replication in an inhibitor-sensitive manner.
AB  - The HIV-1 accessory factor Nef is essential for high-titer viral replication and
      AIDS progression. Nef function requires interaction with many host cell proteins,
      including specific members of the Src kinase family. Here we explored whether Src
      family kinase activation is a conserved property of Nef alleles from a wide range
      of primary HIV-1 isolates and their sensitivity to selective pharmacological
      inhibitors. Representative Nef proteins from the major HIV-1 subtypes A1, A2, B,
      C, F1, F2, G, H, J and K strongly activated Hck and Lyn as well as c-Src to a
      lesser extent, demonstrating for the first time that Src-family kinase activation
      is a highly conserved property of primary M-group HIV-1 Nef isolates. Recently,
      we identified 4-amino substituted diphenylfuropyrimidines (DFPs) that selectively
      inhibit Nef-dependent activation of Src-family kinases as well as HIV
      replication. To determine whether DFP compounds exhibit broad-spectrum Nef
      dependent antiretroviral activity against HIV-1, we first constructed chimeric
      forms of the HIV-1 strain NL4-3 expressing each of the primary Nef alleles. The
      infectivity and replication of these Nef chimeras was indistinguishable from that
      of wild-type virus in two distinct cell lines (U87MG astroglial cells and CEM-T4
      lymphoblasts). Importantly, the 4-aminopropanol and 4-aminobutanol derivatives of
      DFP potently inhibited the replication of all chimeric forms of HIV-1 in both
      U87MG and CEM-T4 cells in a Nef-dependent manner. The antiretroviral effects of
      these compounds correlated with inhibition of Nef-dependent activation of
      endogenous Src-family kinases in the HIV-infected cells. Our results demonstrate
      that the activation of Hck, Lyn and c-Src by Nef is highly conserved among all
      major clades of HIV-1 and that selective targeting of this pathway uniformly
      inhibits HIV-1 replication.

PMID- 22393417
TI  - The dark side is not fastidious--dark septate endophytic fungi of native and
      invasive plants of semiarid sandy areas.
AB  - Dark septate endophytic (DSE) fungi represent a frequent root-colonizing fungal
      group common in environments with strong abiotic stress, such as (semi)arid
      ecosystems. This work aimed to study the DSE fungi colonizing the plants of
      semiarid sandy grasslands with wood steppe patches on the Great Hungarian Plain.
      As we may assume that fungi colonizing both invasive and native species are
      generalists, root associated fungi (RAF) were isolated from eight native and
      three invasive plant species. The nrDNA sequences of the isolates were used for
      identification. To confirm that the fungi were endophytes an artificial
      inoculation system was used to test the isolates: we considered a fungus as DSE
      if it colonized the roots without causing a negative effect on the plant and
      formed microsclerotia in the roots. According to the analyses of the ITS sequence
      of nrDNA the 296 isolates clustered into 41 groups. We found that 14 of these 41
      groups were DSE, representing approximately 60% of the isolates. The main DSE
      groups were generalist and showed no specificity to area or season and colonized
      both native and invasive species, demonstrating that exotic plants are capable of
      using the root endophytic fungi of the invaded areas. The DSE community of the
      region shows high similarity to those found in arid grasslands of North America.
      Taking into account a previous hypothesis about the common root colonizers of
      those grasslands and our results reported here, we hypothesize that plants of
      (semi)arid grasslands share common dominant members of the DSE fungal community
      on a global scale.

PMID- 22393419
TI  - Complex feeding tracks of the sessile herbivorous insect Ophiomyia maura as a
      function of the defense against insect parasitoids.
AB  - Because insect herbivores generally suffer from high mortality due to their
      natural enemies, reducing the risk of being located by natural enemies is of
      critical importance for them, forcing them to develop a variety of defensive
      measures. Larvae of leaf-mining insects lead a sedentary life inside a leaf and
      make conspicuous feeding tracks called mines, exposing themselves to the
      potential risk of parasitism. We investigated the defense strategy of the linear
      leafminer Ophiomyia maura Meigen (Diptera: Agromyzidae), by focusing on its
      mining patterns. We examined whether the leafminer could reduce the risk of being
      parasitized (1) by making cross structures in the inner area of a leaf to deter
      parasitoids from tracking the mines due to complex pathways, and (2) by mining
      along the edge of a leaf to hinder visually searching parasitoids from finding
      mined leaves due to effective background matching of the mined leaves among
      intact leaves. We quantified fractal dimension as mine complexity and area of
      mine in the inner area of the leaf as interior mine density for each sample mine,
      and analyzed whether these mine traits affected the susceptibility of O. maura to
      parasitism. Our results have shown that an increase in mine complexity with the
      development of occupying larvae decreases the probability of being parasitized,
      while interior mine density has no influence on parasitism. These results suggest
      that the larval development increases the host defense ability through increasing
      mine complexity. Thus the feeding pattern of these sessile insects has a
      defensive function by reducing the risk of parasitism.

PMID- 22393418
TI  - Blocking autophagy prevents bortezomib-induced NF-kappaB activation by reducing I
      kappaBalpha degradation in lymphoma cells.
AB  - Here we show that bortezomib induces effective proteasome inhibition and
      accumulation of poly-ubiquitinated proteins in diffuse large B-cell lymphoma
      (DLBCL) cells. This leads to induction of endoplasmic reticulum (ER) stress as
      demonstrated by accumulation of the protein CHOP, as well as autophagy, as
      demonstrated by accumulation of LC3-II proteins. Our data suggest that
      recruitment of both ubiquitinated proteins and LC3-II by p62 directs
      ubiquitinated proteins, including I-kappaBalpha, to the autophagosome.
      Degradation of I-kappaBalpha results in increased NF-kappaB nuclear translocation
      and transcription activity. Since bortezomib treatment promoted I-kappaBalpha
      phosphorylation, ubiquitination and degradation, this suggests that the route of
      I-kappaBalpha degradation was not via the ubiquitin-proteasome degradation
      system. The autophagy inhibitor chloroquine (CQ) significantly inhibited
      bortezomib-induced I-kappaBalpha degradation, increased complex formation with NF
      kappaB and reduced NF-kappaB nuclear translocation and DNA binding activity.
      Importantly, the combination of proteasome and autophagy inhibitors showed
      synergy in killing DLBCL cells. In summary, bortezomib-induced autophagy confers
      relative DLBCL cell drug resistance by eliminating I-kappaBalpha. Inhibition of
      both autophagy and the proteasome has great potential to kill apoptosis-resistant
      lymphoma cells.

PMID- 22393420
TI  - Regional white matter volumes correlate with delay discounting.
AB  - A preference for immediate gratification is a central feature in addictive
      processes. However, the neural structures underlying reward delay tolerance are
      still unclear. Healthy participants (n = 121) completed a delay discounting
      questionnaire assessing the extent to which they prefer smaller immediate rewards
      to larger delayed reward after undergoing magnetic resonance imaging (MRI)
      scanning. Whole brain voxel-based morphometric analysis shows that delay
      discounting severity was negatively correlated with right prefrontal subgyral
      white matter volume and positively correlated with white matter volume in
      parahippocampus/hippocampus, after whole brain correction. This study might
      better our understanding of the neural basis of impulsivity and addiction.

PMID- 22393421
TI  - Postdictive modulation of visual orientation.
AB  - The present study investigated how visual orientation is modulated by subsequent
      orientation inputs. Observers were presented a near-vertical Gabor patch as a
      target, followed by a left- or right-tilted second Gabor patch as a distracter in
      the spatial vicinity of the target. The task of the observers was to judge
      whether the target was right- or left-tilted (Experiment 1) or whether the target
      was vertical or not (Supplementary experiment). The judgment was biased toward
      the orientation of the distracter (the postdictive modulation of visual
      orientation). The judgment bias peaked when the target and distracter were
      temporally separated by 100 ms, indicating a specific temporal mechanism for this
      phenomenon. However, when the visibility of the distracter was reduced via
      backward masking, the judgment bias disappeared. On the other hand, the low
      visibility distracter could still cause a simultaneous orientation contrast,
      indicating that the distracter orientation is still processed in the visual
      system (Experiment 2). Our results suggest that the postdictive modulation of
      visual orientation stems from spatiotemporal integration of visual orientation on
      the basis of a slow feature matching process.

PMID- 22393422
TI  - Implementation of dual-source RF excitation in 3 T MR-scanners allows for nearly
      identical ADC values compared to 1.5 T MR scanners in the abdomen.
AB  - BACKGROUND: To retrospectively and prospectively compare abdominal apparent
      diffusion coefficient (ADC) values obtained within in a 1.5 T system and 3 T
      systems with and without dual-source parallel RF excitation techniques.
      METHODOLOGY/PRINCIPAL FINDINGS: After IRB approval, diffusion-weighted (DW)
      images of the abdomen were obtained on three different MR systems (1.5 T, a first
      generation 3 T, and a second generation 3 T which incorporates dual-source
      parallel RF excitation) on 150 patients retrospectively and 19 volunteers (57
      examinations total) prospectively. Seven regions of interest (ROI) were
      throughout the abdomen were selected to measure the ADC. Statistical analysis
      included independent two-sided t-tests, Mann-Whitney U tests and correlation
      analysis. In the DW images of the abdomen, mean ADC values were nearly identical
      with nonsignificant differences when comparing the 1.5 T and second generation 3
      T systems in all seven anatomical regions in the patient population and six of
      the seven in the volunteer population (p>0.05 in all distributions). The strength
      of correlation measured in the volunteer population between the two scanners in
      the kidneys ranged from r = 0.64-0.88 and in the remaining regions (besides the
      spleen), r>0.85. In the patient population the first generation 3 T scanner had
      different mean ADC values with significant differences (p<0.05) compared to the
      other two scanners in each of the seven distributions. In the volunteer
      population, the kidneys shared similar ADC mean values in comparison to the other
      two scanners with nonsignificant differences. CONCLUSIONS/SIGNIFICANCE: A second
      generation 3 T scanner with dual-source parallel RF excitation provides nearly
      identical ADC values compared with the 1.5 T imaging system in abdominal imaging.

PMID- 22393423
TI  - Assessing the impact of bycatch on dolphin populations: the case of the common
      dolphin in the eastern North Atlantic.
AB  - Fisheries interactions have been implicated in the decline of many marine
      vertebrates worldwide. In the eastern North Atlantic, at least 1000 common
      dolphins (Delphinus delphis) are bycaught each year, particularly in pelagic pair
      trawls. We have assessed the resulting impact of bycatch on this population using
      a demographic modeling approach. We relied on a sample of females stranded along
      the French Atlantic and western Channel coasts. Strandings represent an extensive
      source of demographic information to monitor our study population. Necropsy
      analysis provided an estimate of individual age and reproductive state. Then we
      estimated effective survivorship (including natural and human-induced mortality),
      age at first reproduction and pregnancy rates. Reproductive parameters were
      consistent with literature, but effective survivorship was unexpectedly low.
      Demographic parameters were then used as inputs in two models. A constant
      parameter matrix proposed an effective growth rate of -5.5+/-0.5%, corresponding
      to the current situation (including bycatch mortality). Subsequently,
      deterministic projections suggested that the population would be reduced to 20%
      of its current size in 30 years and would be extinct in 100 years. The
      demographic invariant model suggested a maximum growth rate of +4.5+/-0.09%,
      corresponding to the optimal demographic situation. Then, a risk analysis
      incorporating Potential Biological Removal (PBR), based on two plausible scenarii
      for stock structure suggested that bycatch level was unsustainable for the
      neritic population of the Bay of Biscay under a two-stock scenario. In depth
      assessment of stock structure and improved observer programs to provide
      scientifically robust bycatch estimates are needed. Effective conservation
      measures would be reducing bycatch to less than 50% of the current level in the
      neritic stock to reach PBR. Our approach provided indicators of the status and
      trajectory of the common dolphin population in the eastern North Atlantic and
      therefore proved to be a valuable tool for management, applicable to other
      dolphin populations.

PMID- 22393424
TI  - Marked reduction of AKT1 expression and deregulation of AKT1-associated pathways
      in peripheral blood mononuclear cells of schizophrenia patients.
AB  - BACKGROUND: Recent studies have suggested that deregulated AKT1 signaling is
      associated with schizophrenia. We hypothesized that if this is indeed the case,
      we should observe both decreased AKT1 expression as well as deregulation of AKT1
      regulated pathways in Peripheral Blood Mononuclear Cells (PBMCs) of schizophrenia
      patients. OBJECTIVES: To examine PBMC expression levels of AKT1 in schizophrenia
      patients versus controls, and to examine whether functional biological processes
      in which AKT1 plays an important role are deregulated in schizophrenia patients.
      METHODS/RESULTS: A case-control study, investigating whole-genome PBMC gene
      expression in male, recent onset (<5 years) schizophrenia patients (N = 41) as
      compared to controls (N = 29). Genes, differentially expressed between patients
      and controls were identified using ANOVA with Benjamini-Hochberg correction
      (false discovery rate (FDR) = 0.05). Functional aspects of the deregulated set of
      genes were investigated with the Ingenuity Pathway Analysis (IPA) Software Tool.
      We found significantly decreased PBMC expression of AKT1 (p<0.001, t = -4.25) in
      the patients. AKT1 expression was decreased in antipsychotic-free or -naive
      patients (N = 11), in florid psychotic (N = 20) and in remitted (N = 21)
      patients. A total of 1224 genes were differentially expressed between patients
      and controls (FDR = 0.05). Functional analysis of the entire deregulated gene set
      indicated deregulated canonical pathways involved in a large number of cellular
      processes: immune system, cell adhesion and neuronal guidance, neurotrophins and
      (neural) growth factors, oxidative stress and glucose metabolism, and apoptosis
      and cell-cycle regulation. Many of these processes are associated with AKT1.
      CONCLUSIONS: We show significantly decreased PBMC gene expression of AKT1 in
      male, recent-onset schizophrenia patients. Our observations suggest that
      decreased PBMC AKT1 expression is a stable trait in recent onset, male
      schizophrenia patients. We identified several AKT related cellular processes
      which are potentially affected in these patients, a majority of which play a
      prominent role in current schizophrenia hypotheses.

PMID- 22393425
TI  - Torosaurus is not Triceratops: ontogeny in chasmosaurine ceratopsids as a case
      study in dinosaur taxonomy.
AB  - BACKGROUND: In horned dinosaurs, taxonomy is complicated by the fact that the
      cranial ornament that distinguishes species changes with age. Based on this
      observation, it has been proposed that the genera Triceratops and Torosaurus are
      in fact synonymous, with specimens identified as Torosaurus representing the
      adult form of Triceratops. The hypothesis of synonymy makes three testable
      predictions: 1) the species in question should have similar geographic and
      stratigraphic distributions, 2) specimens assigned to Torosaurus should be more
      mature than those assigned to Triceratops, and 3) intermediates should exist that
      combine features of Triceratops and Torosaurus. The first condition appears to be
      met, but it remains unclear whether the other predictions are borne out by the
      fossil evidence. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the relative
      maturity of Torosaurus and Triceratops specimens by coding skulls for characters
      that vary with maturity, and then using a clustering analysis to arrange them
      into a growth series. We found that a well-defined sequence of changes exists in
      horned dinosaurs: development of cranial ornament occurs in juveniles, followed
      by fusion of the skull roof in subadults, and finally, the epoccipitals,
      epijugals, and rostral fuse to the skull in adults. Using this scheme, we
      identified mature and immature individuals of both Torosaurus and Triceratops.
      Furthermore, we describe the ventral depressions on the frill of Triceratops, and
      show that they differ in shape and position from the parietal fenestrae of
      Torosaurus. Thus, we conclude that these structures are not intermediates between
      the solid frill of Triceratops and the fenestrated frill of Torosaurus.
      CONCLUSIONS/SIGNIFICANCE: Torosaurus is a distinct genus of horned dinosaur, not
      the adult of Triceratops. Our method provides a framework for assessing the
      hypothesis of synonymy through ontogeny in the fossil record.

PMID- 22393426
TI  - Tensor-based morphometry and stereology reveal brain pathology in the complexin1
      knockout mouse.
AB  - Complexins (Cplxs) are small, soluble, regulatory proteins that bind reversibly
      to the SNARE complex and modulate synaptic vesicle release. Cplx1 knockout mice
      (Cplx1(-/-)) have the earliest known onset of ataxia seen in a mouse model,
      although hitherto no histopathology has been described in these mice.
      Nevertheless, the profound neurological phenotype displayed by Cplx1(-/-) mutants
      suggests that significant functional abnormalities must be present in these
      animals. In this study, MRI was used to automatically detect regions where
      structural differences were not obvious when using a traditional histological
      approach. Tensor-based morphometry of Cplx1(-/-) mouse brains showed selective
      volume loss from the thalamus and cerebellum. Stereological analysis of Cplx1(-/
      ) and Cplx1(+/+) mice brain slices confirmed the volume loss in the thalamus as
      well as loss in some lobules of the cerebellum. Finally, stereology was used to
      show that there was loss of cerebellar granule cells in Cplx1(-/-) mice when
      compared to Cplx1(+/+) animals. Our study is the first to describe pathological
      changes in Cplx1(-/-) mouse brain. We suggest that the ataxia in Cplx1(-/-) mice
      is likely to be due to pathological changes in both cerebellum and thalamus.
      Reduced levels of Cplx proteins have been reported in brains of patients with
      neurodegenerative diseases. Therefore, understanding the effects of Cplx
      depletion in brains from Cplx1(-/-) mice may also shed light on the mechanisms
      underlying pathophysiology in disorders in which loss of Cplx1 occurs.

PMID- 22393427
TI  - Ex-vivo clonally expanded B lymphocytes infiltrating colorectal carcinoma are of
      mature immunophenotype and produce functional IgG.
AB  - BACKGROUND: Tumor infiltrating B cells (TiBc) have not yet been investigated in
      detail. This may at least in part be due to technical difficulties. Here we
      describe a straightforward and reproducible method to isolate and culture TiBc
      from primary colorectal carcinomas (CRC). METHODS/RESULTS: TiBc cultures were
      generated by Epstein-Barr virus (EBV) immortalization. With this method,
      monoclonal TiBc cultures were obtained for 14/19 CRCs. As assessed by flow
      cytometry and ELISA, TiBc showed an activated immunophenotype (CD23(+), CD80(+))
      and produced immunoglobulin (Ig; IgG secretion in 55% of the cultures). In
      functional in vitro analysis, most of the IgGs specifically bound to allogeneic
      CRC target cells. These data suggest that TiBc are antigen-experienced and thus
      may exhibit functionality in situ. Additionally, mini-cultures generated from 12
      further CRCs revealed TiBc outgrowth exclusively in the presence of EBV.
      CONCLUSION: In summary, this simple method provides a cellular tool and our data
      set the stage for analysing the bivalent role of TiBc; being antigen-presenting
      cells on the one hand and tumor-specific antibody producers on the other.
      Additionally, the generation of long-term TiBc cultures and their monoclonal Ig
      may serve to identify novel tumor-specific antigens.

PMID- 22393428
TI  - Out of plane distortions of the heme b of Escherichia coli succinate
      dehydrogenase.
AB  - The role of the heme b in Escherichia coli succinate dehydrogenase is highly
      ambiguous and its role in catalysis is questionable. To examine whether heme
      reduction is an essential step of the catalytic mechanism, we generated a series
      of site-directed mutations around the heme binding pocket, creating a library of
      variants with a stepwise decrease in the midpoint potential of the heme from the
      wild-type value of +20 mV down to -80 mV. This difference in midpoint potential
      is enough to alter the reactivity of the heme towards succinate and thus its
      redox state under turnover conditions. Our results show both the steady state
      succinate oxidase and fumarate reductase catalytic activity of the enzyme are not
      a function of the redox potential of the heme. As well, lower heme potential did
      not cause an increase in the rate of superoxide production both in vitro and in
      vivo. The electron paramagnetic resonance (EPR) spectrum of the heme in the wild
      type enzyme is a combination of two distinct signals. We link EPR spectra to
      structure, showing that one of the signals likely arises from an out-of-plane
      distortion of the heme, a saddled conformation, while the second signal
      originates from a more planar orientation of the porphyrin ring.

PMID- 22393429
TI  - Discovery of inhibitors of Leishmania beta-1,2-mannosyltransferases using a click
      chemistry-derived guanosine monophosphate library.
AB  - Leishmania spp. are a medically important group of protozoan parasites that
      synthesize a novel intracellular carbohydrate reserve polymer termed mannogen.
      Mannogen is a soluble homopolymer of beta-1,2-linked mannose residues that
      accumulates in the major pathogenic stages in the sandfly vector and mammalian
      host. While several steps in mannogen biosynthesis have been defined, none of the
      enzymes have been isolated or characterized. We report the development of a
      simple assay for the GDP-mannose-dependent beta-1,2-mannosyltransferases involved
      in mannogen synthesis. This assay utilizes octyl alpha-D-mannopyranoside to prime
      the formation of short mannogen oligomers up to 5 mannose residues. This assay
      was used to screen a focussed library of 44 GMP-triazole adducts for inhibitors.
      Several compounds provided effective inhibition of mannogen beta-1,2
      mannosyltransferases in a cell-free membrane preparation. This assay and
      inhibitor compounds will be useful for dissecting the role of different
      mannosyltransferases in regulating de novo biosynthesis and elongation reactions
      in mannogen metabolism.

PMID- 22393430
TI  - A rapid FACS-based strategy to isolate human gene knockin and knockout clones.
AB  - Gene targeting protocols for mammalian cells remain inefficient and labor
      intensive. Here we describe FASTarget, a rapid, fluorescent cell sorting based
      strategy to isolate rare gene targeting events in human somatic cells. A
      fluorescent protein is used as a means for direct selection of targeted clones
      obviating the need for selection and outgrowth of drug resistant clones.
      Importantly, the use of a promoter-less, ATG-less construct greatly facilitates
      the recovery of correctly targeted cells. Using this method we report successful
      gene targeting in up to 94% of recovered human somatic cell clones. We create
      functional EYFP-tagged knockin clones in both transformed and non-transformed
      human somatic cell lines providing a valuable tool for mammalian cell biology. We
      further demonstrate the use of this technology to create gene knockouts. Using
      this generally applicable strategy we can recover gene targeted clones within
      approximately one month from DNA construct delivery to obtaining targeted
      monoclonal cell lines.

PMID- 22393431
TI  - On docking, scoring and assessing protein-DNA complexes in a rigid-body
      framework.
AB  - We consider the identification of interacting protein-nucleic acid partners using
      the rigid body docking method FTdock, which is systematic and exhaustive in the
      exploration of docking conformations. The accuracy of rigid body docking methods
      is tested using known protein-DNA complexes for which the docked and undocked
      structures are both available. Additional tests with large decoy sets probe the
      efficacy of two published statistically derived scoring functions that contain a
      huge number of parameters. In contrast, we demonstrate that state-of-the-art
      machine learning techniques can enormously reduce the number of parameters
      required, thereby identifying the relevant docking features using a miniscule
      fraction of the number of parameters in the prior works. The present machine
      learning study considers a 300 dimensional vector (dependent on only 15
      parameters), termed the Chemical Context Profile (CCP), where each dimension
      reflects a specific type of protein amino acid-nucleic acid base interaction. The
      CCP is designed to capture the chemical complementarities of the interface and is
      well suited for machine learning techniques. Our objective function is the
      Chemical Context Discrepancy (CCD), which is defined as the angle between the
      native system's CCP vector and the decoy's vector and which serves as a
      substitute for the more commonly used root mean squared deviation (RMSD). We
      demonstrate that the CCP provides a useful scoring function when certain
      dimensions are properly weighted. Finally, we explore how the amino acids on a
      protein's surface can help guide DNA binding, first through long-range
      interactions, followed by direct contacts, according to specific preferences for
      either the major or minor grooves of the DNA.

PMID- 22393432
TI  - The different function of single phosphorylation sites of Drosophila melanogaster
      lamin Dm and lamin C.
AB  - Lamins' functions are regulated by phosphorylation at specific sites but our
      understanding of the role of such modifications is practically limited to the
      function of cdc 2 (cdk1) kinase sites in depolymerization of the nuclear lamina
      during mitosis. In our study we used Drosophila lamin Dm (B-type) to examine the
      function of particular phosphorylation sites using pseudophosphorylated mutants
      mimicking single phosphorylation at experimentally confirmed in vivo phosphosites
      (S(25)E, S(45)E, T(435)E, S(595)E). We also analyzed lamin C (A-type) and its
      mutant S(37)E representing the N-terminal cdc2 (mitotic) site as well as lamin Dm
      R(64)H mutant as a control, non-polymerizing lamin. In the polymerization assay
      we could observe different effects of N-terminal cdc2 site pseudophosphorylation
      on A- and B-type lamins: lamin Dm S(45)E mutant was insoluble, in contrast to
      lamin C S(37)E. Lamin Dm T(435)E (C-terminal cdc2 site) and R(64)H were soluble
      in vitro. We also confirmed that none of the single phosphorylation site
      modifications affected the chromatin binding of lamin Dm, in contrast to the
      lamin C N-terminal cdc2 site. In vivo, all lamin Dm mutants were incorporated
      efficiently into the nuclear lamina in transfected Drosophila S2 and HeLa cells,
      although significant amounts of S(45)E and T(435)E were also located in
      cytoplasm. When farnesylation incompetent mutants were expressed in HeLa cells,
      lamin Dm T(435)E was cytoplasmic and showed higher mobility in FRAP assay.

PMID- 22393433
TI  - An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke
      model.
AB  - We previously showed that middle-aged female rats sustain a larger infarct
      following experimental stroke as compared to younger female rats, and
      paradoxically, estrogen treatment to the older group is neurotoxic. Plasma and
      brain insulin-like growth factor-1 (IGF-1) levels decrease with age. However, IGF
      1 infusion following stroke, prevents estrogen neurotoxicity in middle-aged
      female rats. IGF1 is neuroprotective and well tolerated, but also has potentially
      undesirable side effects. We hypothesized that microRNAs (miRNAs) that target the
      IGF-1 signaling family for translation repression could be alternatively
      suppressed to promote IGF-1-like neuroprotection. Here, we report that two
      conserved IGF pathway regulatory microRNAs, Let7f and miR1, can be inhibited to
      mimic and even extend the neuroprotection afforded by IGF-1. Anti-mir1 treatment,
      as late as 4 hours following ischemia, significantly reduced cortical infarct
      volume in adult female rats, while anti-Let7 robustly reduced both cortical and
      striatal infarcts, and preserved sensorimotor function and interhemispheric
      neural integration. No neuroprotection was observed in animals treated with a
      brain specific miRNA unrelated to IGF-1 (anti-miR124). Remarkably, anti-Let7f was
      only effective in intact females but not males or ovariectomized females
      indicating that the gonadal steroid environment critically modifies miRNA action.
      Let7f is preferentially expressed in microglia in the ischemic hemisphere and
      confirmed in ex vivo cultures of microglia obtained from the cortex. While IGF-1
      was undetectable in microglia harvested from the non-ischemic hemisphere, IGF-1
      was expressed by microglia obtained from the ischemic cortex and was further
      elevated by anti-Let7f treatment. Collectively these data support a novel miRNA
      based therapeutic strategy for neuroprotection following stroke.

PMID- 22393434
TI  - Blue whales respond to anthropogenic noise.
AB  - Anthropogenic noise may significantly impact exposed marine mammals. This work
      studied the vocalization response of endangered blue whales to anthropogenic
      noise sources in the mid-frequency range using passive acoustic monitoring in the
      Southern California Bight. Blue whales were less likely to produce calls when mid
      frequency active sonar was present. This reduction was more pronounced when the
      sonar source was closer to the animal, at higher sound levels. The animals were
      equally likely to stop calling at any time of day, showing no diel pattern in
      their sensitivity to sonar. Conversely, the likelihood of whales emitting calls
      increased when ship sounds were nearby. Whales did not show a differential
      response to ship noise as a function of the time of the day either. These results
      demonstrate that anthropogenic noise, even at frequencies well above the blue
      whales' sound production range, has a strong probability of eliciting changes in
      vocal behavior. The long-term implications of disruption in call production to
      blue whale foraging and other behaviors are currently not well understood.

PMID- 22393435
TI  - Pentachlorophenol induction of the Pseudomonas aeruginosa mexAB-oprM efflux
      operon: involvement of repressors NalC and MexR and the antirepressor ArmR.
AB  - Pentachlorophenol (PCP) induced expression of the NalC repressor-regulated PA3720
      armR operon and the MexR repressor-controlled mexAB-oprM multidrug efflux operon
      of Pseudomonas aeruginosa. PCP's induction of PA3720-armR resulted from its
      direct modulation of NalC, the repressor's binding to PA3720-armR promoter
      containing DNA as seen in electromobility shift assays (EMSAs) being obviated in
      the presence of this agent. The NalC binding site was localized to an inverted
      repeat (IR) sequence upstream of PA3720-armR and overlapping a promoter region
      whose transcription start site was mapped. While modulation of MexR by the ArmR
      anti-repressor explains the upregulation of mexAB-oprM in nalC mutants
      hyperexpressing PA3720-armR, the induction of mexAB-oprM expression by PCP is not
      wholly explainable by PCP induction of PA3720-armR and subsequent ArmR modulation
      of MexR, inasmuch as armR deletion mutants still showed PCP-inducible mexAB-oprM
      expression. PCP failed, however, to induce mexAB-oprM in a mexR deletion strain,
      indicating that MexR was required for this, although PCP did not modulate MexR
      binding to mexAB-oprM promoter-containing DNA in vitro. One possibility is that
      MexR responds to PCP-generated in vivo effector molecules in controlling mexAB
      oprM expression in response to PCP. PCP is an unlikely effector and substrate for
      NalC and MexAB-OprM--its impact on NalC binding to the PA3720-armR promoter DNA
      occurred only at high uM levels--suggesting that it mimics an intended phenolic
      effector/substrate(s). In this regard, plants are an abundant source of phenolic
      antimicrobial compounds and, so, MexAB-OprM may function to protect P. aeruginosa
      from plant antimicrobials that it encounters in nature.

PMID- 22393436
TI  - Caenorhabditis elegans maintains highly compartmentalized cellular distribution
      of metals and steep concentration gradients of manganese.
AB  - Bioinorganic chemistry is critical to cellular function. Homeostasis of manganese
      (Mn), for example, is essential for life. A lack of methods for direct in situ
      visualization of Mn and other biological metals within intact multicellular
      eukaryotes limits our understanding of management of these metals. We provide the
      first quantitative subcellular visualization of endogenous Mn concentrations
      (spanning two orders of magnitude) associated with individual cells of the
      nematode, Caenorhabditis elegans.

PMID- 22393437
TI  - Head lice in Norwegian households: actions taken, costs and knowledge.
AB  - INTRODUCTION: Head lice infestations cause distress in many families. A well
      founded strategy to reduce head lice prevalence must shorten the infectious
      period of individual hosts. To develop such a strategy, information about the
      actions taken (inspection, treatment and informing others about own
      infestations), level of knowledge and costs is needed. The present study is the
      first to consider all these elements combined. MATERIALS AND METHODS: A
      questionnaire was answered by 6203 households from five geographically separated
      municipalities in Norway. RESULTS: 94% of the households treated members with
      pediculicides when head lice were discovered. Nearly half of the households
      checked biannually or not at all. Previous occurrence of head lice and multiple
      children in a household improved both checking frequency and method. More than
      90% of the households informed close contacts about their own pediculosis. Direct
      costs of pediculosis were low (less than ?6.25 yearly) for 70% of the households,
      but the ability to pay for pediculicides decreased with the number of head lice
      infestations experienced. One in three households kept children from school
      because of pediculosis. Other widespread misconceptions, such as that excessive
      cleaning is necessary to fight head lice, may also add unnecessary burden to
      households. School affiliation had a significant effect on checking frequency and
      method, knowledge and willingness to inform others about own pediculosis.
      CONCLUSIONS: Increased checking frequencies appear to be the most important
      element to reduce head lice prevalence in Norway and should be a primary focus of
      future strategies. National campaigns directed through schools to individual
      households, might be an important tool to achieve this goal. In addition to
      improving actions taken, such campaigns should also provide accurate information
      to reduce costs and enhance the level of knowledge about head lice in households.

PMID- 22393438
TI  - Global monthly water scarcity: blue water footprints versus blue water
      availability.
AB  - Freshwater scarcity is a growing concern, placing considerable importance on the
      accuracy of indicators used to characterize and map water scarcity worldwide. We
      improve upon past efforts by using estimates of blue water footprints
      (consumptive use of ground- and surface water flows) rather than water
      withdrawals, accounting for the flows needed to sustain critical ecological
      functions and by considering monthly rather than annual values. We analyzed 405
      river basins for the period 1996-2005. In 201 basins with 2.67 billion
      inhabitants there was severe water scarcity during at least one month of the
      year. The ecological and economic consequences of increasing degrees of water
      scarcity--as evidenced by the Rio Grande (Rio Bravo), Indus, and Murray-Darling
      River Basins--can include complete desiccation during dry seasons, decimation of
      aquatic biodiversity, and substantial economic disruption.

PMID- 22393439
TI  - Fatty liver index predicts further metabolic deteriorations in women with
      previous gestational diabetes.
AB  - BACKGROUND AND AIMS: Determinants of fatty liver (FL) might be predictive for
      further deterioration in insulin resistance (IR) in women with previous
      gestational diabetes (pGDM). The aim was to evaluate the association between
      pGDM, FL and future manifestation of type 2 diabetes (T2DM) by a detailed
      pathophysiological characterization early after pregnancy. METHODS: 68 pGDM and
      29 healthy controls were included 3-6 months after delivery and underwent
      specific metabolic assessments: status of IR was determined via oral- and
      intravenous-glucose-tolerance-tests with analysis of proinflammatory factors and
      kinetics of free-fatty-acids (FFA). According to the fatty-liver-index (FLI),
      pGDMs were categorized into three groups with low (FLI<=20), intermediate
      (20<FLI<60) and high (FLI>=60) risk for FL to assess differences in metabolic
      parameters at baseline as well as in the 10-year incidence for T2DM. Accuracy of
      FLI was proven with 1H-magnetic-resonance-spectroscopy. RESULTS: FL was strongly
      associated with IR in pGDM. pGDM with FLI>=60 showed significantly increased
      interleukin-6, plasminogen-activator-inhibitor-1, tissue-plasminogen-activator,
      fibrinogen and increased ultrasensitive-C-reactive-protein compared to the low
      risk group (FLI<=20). Analysis of FFA indicated a less pronounced decrease of
      plasma FFA levels during the oral-glucose-tolerance-test in subjects with
      FLI>=60. History of GDM plus FLI>=60 conferred a high risk for the manifestation
      of diabetes over 10 years of observation as compared to pGDMs with FLI<=20
      (HR:7.85, Cl:2.02-30.5, p = 0.003). CONCLUSION: FL is closely linked to GDM,
      especially to IR and inflammation. Most interestingly, subjects with the highest
      FLI values showed significant alterations in FFA kinetics and a higher risk to
      develop T2DM in future.

PMID- 22393440
TI  - Detection and quantification of Leptospira interrogans in hamster and rat kidney
      samples: immunofluorescent imprints versus real-time PCR.
AB  - A major limitation in the clinical management and experimental research of
      leptospirosis is the poor performance of the available methods for the direct
      detection of leptospires. In this study, we compared real-time PCR (qPCR),
      targeting the lipL32 gene, with the immunofluorescent imprint method (IM) for the
      detection and quantification of leptospires in kidney samples from the rat and
      hamster experimental models of leptospirosis. Using a virulent strain of
      Leptospira interrogans serovar Copenhageni, a chronic infection was established
      in the rat model, which were euthanized 28 days post-infection, while the hamster
      model simulated an acute infection and the hamsters were euthanized eight days
      after inoculation. Leptospires in the kidney samples were detected using culture
      isolation, qPCR and the IM, and quantified using qPCR and the IM. In both the
      acute and chronic infection models, the correlation between quantification by
      qPCR and the IM was found to be positive and statistically significant (P<0.05).
      Therefore, this study demonstrates that the IM is a viable alternative for not
      only the detection but also the quantification of leptospires, particularly when
      the use of qPCR is not feasible.

PMID- 22393441
TI  - In-depth characterization of viral isolates from plasma and cells compared with
      plasma circulating quasispecies in early HIV-1 infection.
AB  - BACKGROUND: The use of in vitro models to unravel the phenotypic characteristics
      of circulating viral variants is key to understanding HIV-1 pathogenesis but
      limited by the availability of primary viral isolates from biological samples.
      However, overall in vivo genetic variability of HIV-1 within a subject may not be
      reflected in the viable viral population obtained after isolation. Although
      several studies have tried to determine whether viral populations expanded in
      vitro are representative of in vivo findings, the answer remains unclear due to
      the reduced number of clonal sequences analyzed or samples compared. In order to
      overcome previous experimental limitations, here we applied Deep Pyrosequencing
      (DPS) technology in combination with phenotypic experiments to analyze and
      compare with unprecedented detail the composition of viral isolates and in vivo
      quasispecies. METHODOLOGY/PRINCIPAL FINDINGS: We amplified by DPS HIV-1 genomic
      regions covering gag, protease, integrase and env-V3 to characterize paired
      isolates from plasma and peripheral blood mononuclear cells and compare them with
      total plasma viral RNA in four recently HIV-1 infected subjects. Our study
      demonstrated the presence of unique haplotypes scattered between sample types
      with conservation of major variants. In addition, no differences in intra- and
      inter-population encoded protein variability were found between the different
      types of isolates or when these were compared to plasma viral RNA within
      subjects. Additionally, in vitro experiments demonstrated phenotypic similarities
      in terms of replicative capacity and co-receptor usage between viral isolates and
      plasma viral RNA. CONCLUSION: This study is the first in-depth comparison and
      characterization of viral isolates from different sources and plasma circulating
      quasispecies using DPS in recently HIV-1 infected subjects. Our data supports the
      use of primary isolates regardless of their plasma or cellular origin to define
      genetic variability and biological traits of circulating HIV-1 quasispecies.

PMID- 22393442
TI  - Does day length affect winter bird distribution? Testing the role of an elusive
      variable.
AB  - Differences in day length may act as a critical factor in bird biology by
      introducing time constraints in energy acquisition during winter. Thus,
      differences in day length might operate as a main determinant of bird abundance
      along latitudinal gradients. This work examines the influence of day length on
      the abundance of wintering crested tits (Lophophanes cristatus) in 26 localities
      of Spanish juniper (Juniperus thurifera) dwarf woodlands (average height of 5 m)
      located along a latitudinal gradient in the Spanish highlands, while controlling
      for the influence of food availability, minimum night temperature, habitat
      structure and landscape characteristics. Top regression models in the AIC
      framework explained 56% of variance in bird numbers. All models incorporated day
      length as the variable with the highest magnitude effect. Food availability also
      played an important role, although only the crop of ripe juniper fruits, but not
      arthropods, positively affected crested tit abundance. Differences in vegetation
      structure across localities had also a strong positive effect (average tree
      height and juniper tree density). Geographical variation in night temperature had
      no influence on crested tit distribution, despite the low winter temperatures
      reached in these dwarf forests. This paper demonstrates for the first time that
      winter bird abundance increases with day length after controlling for the effect
      of other environmental variables. Winter average difference in day length was
      only 10.5 minutes per day along the 1 degrees 47' latitudinal interval (190 km)
      included in this study. This amount of time, which reaches 13.5 h accumulated
      throughout the winter season, appears to be large enough to affect the long-term
      energy budget of small passerines during winter and to shape the distribution of
      winter bird abundance under restrictive environmental conditions.

PMID- 22393443
TI  - Defects in mitochondrial dynamics and metabolomic signatures of evolving
      energetic stress in mouse models of familial Alzheimer's disease.
AB  - BACKGROUND: The identification of early mechanisms underlying Alzheimer's Disease
      (AD) and associated biomarkers could advance development of new therapies and
      improve monitoring and predicting of AD progression. Mitochondrial dysfunction
      has been suggested to underlie AD pathophysiology, however, no comprehensive
      study exists that evaluates the effect of different familial AD (FAD) mutations
      on mitochondrial function, dynamics, and brain energetics. METHODS AND FINDINGS:
      We characterized early mitochondrial dysfunction and metabolomic signatures of
      energetic stress in three commonly used transgenic mouse models of FAD.
      Assessment of mitochondrial motility, distribution, dynamics, morphology, and
      metabolomic profiling revealed the specific effect of each FAD mutation on the
      development of mitochondrial stress and dysfunction. Inhibition of mitochondrial
      trafficking was characteristic for embryonic neurons from mice expressing mutant
      human presenilin 1, PS1(M146L) and the double mutation of human amyloid precursor
      protein APP(Tg2576) and PS1(M146L) contributing to the increased susceptibility
      of neurons to excitotoxic cell death. Significant changes in mitochondrial
      morphology were detected in APP and APP/PS1 mice. All three FAD models
      demonstrated a loss of the integrity of synaptic mitochondria and energy
      production. Metabolomic profiling revealed mutation-specific changes in the
      levels of metabolites reflecting altered energy metabolism and mitochondrial
      dysfunction in brains of FAD mice. Metabolic biomarkers adequately reflected
      gender differences similar to that reported for AD patients and correlated well
      with the biomarkers currently used for diagnosis in humans. CONCLUSIONS: Mutation
      specific alterations in mitochondrial dynamics, morphology and function in FAD
      mice occurred prior to the onset of memory and neurological phenotype and before
      the formation of amyloid deposits. Metabolomic signatures of mitochondrial stress
      and altered energy metabolism indicated alterations in nucleotide, Krebs cycle,
      energy transfer, carbohydrate, neurotransmitter, and amino acid metabolic
      pathways. Mitochondrial dysfunction, therefore, is an underlying event in AD
      progression, and FAD mouse models provide valuable tools to study early molecular
      mechanisms implicated in AD.

PMID- 22393444
TI  - Local and regional re-establishment of cellular immunity during curative
      antibiotherapy of murine Mycobacterium ulcerans infection.
AB  - BACKGROUND: Buruli ulcer (BU) is a neglected necrotizing disease of the skin,
      subcutaneous tissue and bone, caused by Mycobacterium ulcerans. BU pathogenesis
      is associated with mycolactone, a lipidic exotoxin with cytotoxic and
      immunosuppressive properties. Since 2004, the World Health Organization
      recommends the treatment of BU with a combination of rifampicin and streptomycin
      (RS). Histological analysis of human tissue samples suggests that such antibiotic
      treatment reverses the mycolactone-induced local immunosuppression, leading to
      increased inflammatory infiltrations and phagocytosis of bacilli.
      METHODOLOGY/PRINCIPAL FINDINGS: We used a mouse model of M. ulcerans footpad
      infection, followed by combined RS treatment. Time-lapsed analyses of macroscopic
      lesions, bacterial burdens, histology and immunohistochemistry were performed in
      footpads. We also performed CFU counts, histology and immunohistochemistry in the
      popliteal draining lymph nodes (DLN). We observed a shift in the cellular
      infiltrates from a predominantly neutrophilic/macrophagic to a
      lymphocytic/macrophagic profile in the infected footpads of antibiotic-treated
      mice. This shift occurred before the elimination of viable M. ulcerans organisms,
      which were ultimately eradicated as demonstrated by the administration of
      dexamethasone. This reduction of bacillary loads was accompanied by an increased
      expression of inducible nitric oxide synthase (NOS2 or iNOS). Predominantly
      mononuclear infiltrates persisted in the footpads during and after treatment,
      coincident with the long persistence of non-viable poorly stained acid-fast
      bacilli (AFB). We additionally observed that antibiotherapy prevented DLN
      destruction and lymphocyte depletion, which occurs during untreated experimental
      infections. CONCLUSIONS/SIGNIFICANCE: Early RS treatment of M. ulcerans mouse
      footpad infections results in the rapid elimination of viable bacilli with
      pathogen eradication. However, non-viable AFB persisted for several months after
      lesion sterilization. This RS regimen prevented DLN destruction, allowing the
      rapid re-establishment of local and regional cell mediated immune responses
      associated with macrophage activation. Therefore it is likely that this re
      establishment of protective cellular immunity synergizes with antibiotherapy.

PMID- 22393445
TI  - The structure of Mediterranean rocky reef ecosystems across environmental and
      human gradients, and conservation implications.
AB  - Historical exploitation of the Mediterranean Sea and the absence of rigorous
      baselines makes it difficult to evaluate the current health of the marine
      ecosystems and the efficacy of conservation actions at the ecosystem level. Here
      we establish the first current baseline and gradient of ecosystem structure of
      nearshore rocky reefs at the Mediterranean scale. We conducted underwater surveys
      in 14 marine protected areas and 18 open access sites across the Mediterranean,
      and across a 31-fold range of fish biomass (from 3.8 to 118 g m(-2)). Our data
      showed remarkable variation in the structure of rocky reef ecosystems.
      Multivariate analysis showed three alternative community states: (1) large fish
      biomass and reefs dominated by non-canopy algae, (2) lower fish biomass but
      abundant native algal canopies and suspension feeders, and (3) low fish biomass
      and extensive barrens, with areas covered by turf algae. Our results suggest that
      the healthiest shallow rocky reef ecosystems in the Mediterranean have both large
      fish and algal biomass. Protection level and primary production were the only
      variables significantly correlated to community biomass structure. Fish biomass
      was significantly larger in well-enforced no-take marine reserves, but there were
      no significant differences between multi-use marine protected areas (which allow
      some fishing) and open access areas at the regional scale. The gradients reported
      here represent a trajectory of degradation that can be used to assess the health
      of any similar habitat in the Mediterranean, and to evaluate the efficacy of
      marine protected areas.

PMID- 22393446
TI  - Cationic amino acid uptake constitutes a metabolic regulation mechanism and
      occurs in the flagellar pocket of Trypanosoma cruzi.
AB  - Trypanosomatids' amino acid permeases are key proteins in parasite metabolism
      since they participate in the adaptation of parasites to different environments.
      Here, we report that TcAAP3, a member of a Trypanosoma cruzi multigene family of
      permeases, is a bona fide arginine transporter. Most higher eukaryotic cells
      incorporate cationic amino acids through a single transporter. In contrast, T.
      cruzi can recognize and transport cationic amino acids by mono-specific permeases
      since a 100-fold molar excess of lysine could not affect the arginine transport
      in parasites that over-express the arginine permease (TcAAP3 epimastigotes). In
      order to test if the permease activity regulates downstream processes of the
      arginine metabolism, the expression of the single T. cruzi enzyme that uses
      arginine as substrate, arginine kinase, was evaluated in TcAAP3 epimastigotes. In
      this parasite model, intracellular arginine concentration increases 4-folds and
      ATP level remains constant until cultures reach the stationary phase of growth,
      with decreases of about 6-folds in respect to the controls. Interestingly,
      Western Blot analysis demonstrated that arginine kinase is significantly down
      regulated during the stationary phase of growth in TcAAP3 epimastigotes. This
      decrease could represent a compensatory mechanism for the increase in ATP
      consumption as a consequence of the displacement of the reaction equilibrium of
      arginine kinase, when the intracellular arginine concentration augments and the
      glucose from the medium is exhausted. Using immunofluorescence techniques we also
      determined that TcAAP3 and the specific lysine transporter TcAAP7 co-localize in
      a specialized region of the plasma membrane named flagellar pocket, staining a
      single locus close to the flagellar pocket collar. Taken together these data
      suggest that arginine transport is closely related to arginine metabolism and
      cell energy balance. The clinical relevance of studying trypanosomatids'
      permeases relies on the possibility of using these molecules as a route of entry
      of therapeutic drugs.

PMID- 22393447
TI  - CMV infection attenuates the disease course in a murine model of multiple
      sclerosis.
AB  - Recent evidence in multiple sclerosis (MS) suggests that active CMV infection may
      result in more benign clinical disease. The goal of this pilot study was to
      determine whether underlying murine CMV (MCMV) infection affects the course of
      the Theiler's murine encephalitis virus (TMEV) induced murine model of MS. A
      group of eight TMEV-infected mice were co-infected with MCMV at 2 weeks prior to
      TMEV infection while a second group of TMEV-infected mice received MCMV two weeks
      post TMEV. We also used 2 control groups, where at the above time points MCMV was
      replaced with PBS. Outcome measures included (1) monthly monitoring of disability
      via rotarod for 8 months; (2) in vivo MRI for brain atrophy studies and (3) FACS
      analysis of brain infiltrating lymphocytes at 8 months post TMEV infection. Co
      infection with MCMV influenced the disease course in mice infected prior to TMEV
      infection. In this group, rotarod detectable motor performance was significantly
      improved starting 3 months post-infection and beyond (p<=0.024). In addition,
      their brain atrophy was close to 30% reduced at 8 months, but this was only
      present as a trend due to low power (p = 0.19). A significant reduction in the
      proportion of brain infiltrating CD3+ cells was detected in this group (p =
      0.026), while the proportion of CD45+ Mac1+ cells significantly increased (p =
      0.003). There was also a strong trend for a reduced proportion of CD4+ cells (p =
      0.17) while CD8 and B220+ cell proportion did not change. These findings support
      an immunomodulatory effect of MCMV infection in this MS model. Future studies in
      this co-infection model will provide insight into mechanisms which modulate the
      development of demyelination and may be utilized for the development of novel
      therapeutic strategies.

PMID- 22393448
TI  - Decrease of miR-146b-5p in monocytes during obesity is associated with loss of
      the anti-inflammatory but not insulin signaling action of adiponectin.
AB  - BACKGROUND: Low adiponectin, a well-recognized antidiabetic adipokine, has been
      associated with obesity-related inflammation, oxidative stress and insulin
      resistance. Globular adiponectin is an important regulator of the interleukin-1
      receptor-associated kinase (IRAK)/NFkappaB pathway in monocytes of obese
      subjects. It protects against inflammation and oxidative stress by inducing
      IRAK3. microRNA (miR)-146b-5p inhibits NFkappaB-mediated inflammation by targeted
      repression of IRAK1 and TNF receptor-associated factor-6 (TRAF6). Therefore, we
      measured the expression of miR-146b-5p in monocytes of obese subjects. Because it
      was low we determined the involvement of this miR in the anti-inflammatory,
      antioxidative and insulin signaling action of globular adiponectin. METHODS: miR
      146b-5p expression in monocytes of obese subjects was determined by qRT-PCR. The
      effect of miR-146b-5p silencing on molecular markers of inflammation, oxidative
      stress and insulin signaling and the association with globular adiponectin was
      assessed in human THP-1 monocytes. RESULTS: miR-146b-5p was downregulated in
      monocytes of obese persons. Low globular adiponectin decreased miR-146b-5p and
      IRAK3 in THP-1 monocytes, associated with increased mitochondrial reactive oxygen
      species (ROS). Intracellular ROS and insulin receptor substrate-1 (IRS1) protein
      were unchanged. Silencing of miR-146b-5p with an antisense inhibitor resulted in
      increased expression of IRAK1 and TRAF6 leading to more NFkappaB p65 DNA binding
      activity and TNFalpha. As a response IRAK3 and IRS1 protein increased.
      Mitochondrial and intracellular ROS production did not increase despite more
      inflammation. In addition, exposure of miR-146b-5p-depleted THP-1 monocytes to
      high levels of globular adiponectin resulted in an increased production of
      TNFalpha and intracellular ROS. Still, they did not lose their potential to
      increase IRAK3 and IRS1 protein and to decrease mitochondrial ROS. CONCLUSION:
      miR-146b-5p, decreased in monocytes during obesity, is a major mediator of the
      anti-inflammatory action of globular adiponectin. It appears not to be involved
      in insulin signaling possibly by protective response of IRAK3 and lack of
      mitochondrial ROS production.

PMID- 22393449
TI  - Bearded reedlings adjust their pair-bond behaviour in relation to the sex and
      attractiveness of unpaired conspecifics.
AB  - An individual's investment in mating or keeping a pair bond intact may be
      influenced not only by the attractiveness of its current mate, but also by that
      of other potential mates. In this study, we investigated the effect of relative
      attractiveness on pair-bond behaviour in bearded reedlings, Panurus biarmicus. We
      showed that mate attractiveness, in terms of beard length in males and tail
      length in females, influenced courtship behaviour when the pair was kept
      isolated. In the presence of a conspecific, contact initiations within a pair
      increased. This increment was mainly related to the sex of the unpaired
      conspecific, however, and less to differences in attractiveness between the
      current partner and the unpaired conspecific. Female contact initiations towards
      potential extra mates were independent of male attractiveness, whereas male
      contact behaviour was significantly influenced by female attractiveness. However,
      females displayed more contact initiations to their current mate when they were
      less attractive than the unpaired females. Males decreased their overtures
      towards other females with increasing attractiveness of their current mates.
      Overall, our results suggested that, when there was a risk of losing their mate,
      bearded reedlings adjust their pair-bond investment mainly in response to the
      presence or absence of a competitor, and fine-tune investment to a lesser extent
      in response to the attractiveness of that potential competitor.

PMID- 22393450
TI  - Differential differences in methylation status of putative imprinted genes among
      cloned swine genomes.
AB  - DNA methylation is a major epigenetic modification in the mammalian genome that
      regulates crucial aspects of gene function. Mammalian cloning by somatic cell
      nuclear transfer (SCNT) often results in gestational or neonatal failure with
      only a small proportion of manipulated embryos producing live births. Many of the
      embryos that survive to term later succumb to a variety of abnormalities that are
      likely due to inappropriate epigenetic reprogramming. Aberrant methylation
      patterns of imprinted genes in cloned cattle and mice have been elucidated, but
      few reports have analyzed the cloned pig genome. Four surviving cloned sows that
      were created by ear fibroblast nuclear transfer, each with a different life span
      and multiple organ defects, such as heart defects and bone growth delay, were
      used as epigenetic study materials. First, we identified four putative
      differential methylation regions (DMR) of imprinted genes in the wild-type pig
      genome, including two maternally imprinted loci (INS and IGF2) and two paternally
      imprinted loci (H19 and IGF2R). Aberrant DNA methylation, either hypermethylation
      or hypomethylation, commonly appeared in H19 (45% of imprinted loci
      hypermethylated vs. 30% hypomethylated), IGF2 (40% vs. 0%), INS (50% vs. 5%), and
      IGF2R (15% vs. 45%) in multiple tissues from these four cloned sows compared with
      wild-type pigs. Our data suggest that aberrant epigenetic modifications occur
      frequently in the genome of cloned swine. Even with successful production of
      cloned swine that avoid prenatal or postnatal death, the perturbation of
      methylation in imprinted genes still exists, which may be one of reason for their
      adult pathologies and short life. Understanding the aberrant pattern of gene
      imprinting would permit improvements in future cloning techniques.

PMID- 22393451
TI  - Digit ratio predicts sense of direction in women.
AB  - The relative length of the second-to-fourth digits (2D:4D) has been linked with
      prenatal androgen in humans. The 2D:4D is sexually dimorphic, with lower values
      in males than females, and appears to correlate with diverse measures of
      behavior. However, the relationship between digit ratio and cognition, and
      spatial cognition in particular, has produced mixed results. In the present
      study, we hypothesized that spatial tasks separating cue conditions that either
      favored female or male strategies would examine this structure-function
      correlation with greater precision. Previous work suggests that males are better
      in the use of directional cues than females. In the present study, participants
      learned a target location in a virtual landscape environment, in conditions that
      contained either all directional (i.e., distant or compass bearing) cues, or all
      positional (i.e., local, small objects) cues. After a short delay, participants
      navigated back to the target location from a novel starting location. Males had
      higher accuracy in initial search direction than females in environments with all
      directional cues. Lower digit ratio was correlated with higher accuracy of
      initial search direction in females in environments with all directional cues.
      Mental rotation scores did not correlate with digit ratio in either males or
      females. These results demonstrate for the first time that a sex difference in
      the use of directional cues, i.e., the sense of direction, is associated with
      more male-like digit ratio.

PMID- 22393452
TI  - Overexpression of ZEB2 in peritumoral liver tissue correlates with favorable
      survival after curative resection of hepatocellular carcinoma.
AB  - BACKGROUND: ZEB2 has been suggested to mediate EMT and disease aggressiveness in
      several types of human cancers. However, the expression patterns of ZEB2 in
      hepatocellular carcinoma (HCC) and its effect on prognosis of HCC patients
      treated with hepatectomy are unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this
      study, the methods of tissue microarray and immunohistochemistry (IHC) were
      utilized to investigate ZEB2 expression in HCC and peritumoral liver tissue
      (PLT). Receiver operating characteristic (ROC), spearman's rank correlation,
      Kaplan-Meier plots and Cox proportional hazards regression model were used to
      analyze the data. Up-regulated expression of cytoplasmic/nuclear ZEB2 protein was
      observed in the majority of PLTs, when compared to HCCs. Further analysis showed
      that overexpression of cytoplasmic ZEB2 in HCCs was inversely correlated with AFP
      level, tumor size and differentiation (P<0.05). Also, overexpression of
      cytoplasmic ZEB2 in PLTs correlated with lower AFP level (P<0.05). In univariate
      survival analysis, a significant association between overexpression of
      cytoplasmic ZEB2 by HCCs/PLTs and longer patients' survival was found (P<0.05).
      Importantly, cytoplasmic ZEB2 expression in PLTs was evaluated as an independent
      prognostic factor in multivariate analysis (P<0.05). Consequently, a new
      clinicopathologic prognostic model with cytoplasmic ZEB2 expression (including
      HCCs and PLTs) was constructed. The model could significantly stratify risk (low,
      intermediate and high) for overall survival (P = 0.002).
      CONCLUSIONS/SIGNIFICANCE: Our findings provide a basis for the concept that
      cytoplasmic ZEB2 expressed by PLTs can predict the postoperative survival of
      patients with HCC. The combined cytoplasmic ZEB2 prognostic model may become a
      useful tool for identifying patients with different clinical outcomes.

PMID- 22393453
TI  - Search filters for finding prognostic and diagnostic prediction studies in
      Medline to enhance systematic reviews.
AB  - BACKGROUND: The interest in prognostic reviews is increasing, but to properly
      review existing evidence an accurate search filer for finding prediction research
      is needed. The aim of this paper was to validate and update two previously
      introduced search filters for finding prediction research in Medline: the Ingui
      filter and the Haynes Broad filter. METHODOLOGY/PRINCIPAL FINDINGS: Based on a
      hand search of 6 general journals in 2008 we constructed two sets of papers. Set
      1 consisted of prediction research papers (n = 71), and set 2 consisted of the
      remaining papers (n = 1133). Both search filters were validated in two ways,
      using diagnostic accuracy measures as performance measures. First, we compared
      studies in set 1 (reference) with studies retrieved by the search strategies as
      applied in Medline. Second, we compared studies from 4 published systematic
      reviews (reference) with studies retrieved by the search filter as applied in
      Medline. Next--using word frequency methods--we constructed an additional search
      string for finding prediction research. Both search filters were good in
      identifying clinical prediction models: sensitivity ranged from 0.94 to 1.0 using
      our hand search as reference, and 0.78 to 0.89 using the systematic reviews as
      reference. This latter performance measure even increased to around 0.95 (range
      0.90 to 0.97) when either search filter was combined with the additional string
      that we developed. Retrieval rate of explorative prediction research was poor,
      both using our hand search or our systematic review as reference, and even
      combined with our additional search string: sensitivity ranged from 0.44 to 0.85.
      CONCLUSIONS/SIGNIFICANCE: Explorative prediction research is difficult to find in
      Medline, using any of the currently available search filters. Yet, application of
      either the Ingui filter or the Haynes broad filter results in a very low number
      missed clinical prediction model studies.

PMID- 22393454
TI  - Characterization of the fungal microbiota (mycobiome) in healthy and dandruff
      afflicted human scalps.
AB  - The human scalp harbors a vast community of microbial mutualists, the composition
      of which is difficult to elucidate as many of the microorganisms are not
      culturable using current culture techniques. Dandruff, a common scalp disorder,
      is known as a causative factor of a mild seborrheic dermatitis as well as
      pityriasis versicolor, seborrheic dermatitis, and atopic dermatitis. Lipophilic
      yeast Malassezia is widely accepted to play a role in dandruff, but relatively
      few comprehensive studies have been reported. In order to investigate fungal
      biota and genetic resources of dandruff, we amplified the 26S rRNA gene from
      samples of healthy scalps and dandruff-afflicted scalps. The sequences were
      analyzed by a high throughput method using a GS-FLX 454 pyrosequencer. Of the
      74,811 total sequence reads, Basidiomycota (Filobasidium spp.) was the most
      common phylum associated with dandruff. In contrast, Ascomycota (Acremonium spp.)
      was common in the healthy scalps. Our results elucidate the distribution of
      fungal communities associated with dandruff and provide new avenues for the
      potential prevention and treatment of dandruff.

PMID- 22393455
TI  - RNA interference can rebalance the nitrogen sink of maize seeds without losing
      hard endosperm.
AB  - BACKGROUND: One of the goals of plant breeding is to create crops to provide
      better nutrition for humans and livestock. Insufficient intake of protein is one
      of the most severe factors affecting the growth and development of children in
      developing countries. More than a century ago, in 1896, Hopkins initiated the
      well-known Illinois long-term selection for maize seed protein concentration,
      yielding four protein strains. By continuously accumulating QTLs, Illinois High
      Protein (IHP) reached a protein level 2.5-fold higher than normal maize, with the
      most increased fraction being the zein protein, which was shown to contain no
      lysine soon after the long-term selection program initiated. Therefore, IHP is of
      little value for feeding humans and monogastric animals. Although high-lysine
      lines of non-vitreous mutants were based on reduced zeins, the kernel soft
      texture precluded their practical use. Kernel hardness in opaque 2 (o2) could be
      restored in quality protein maize (QPM) with quantitative trait loci called o2
      modifiers (Mo2s), but those did not increase total protein levels. METHODS: The
      most predominant zeins are the 22- and 19-kDa alpha-zeins. To achieve a
      combination of desired traits, we used RNA interference (RNAi) against both alpha
      zeins in IHP and evaluated the silencing effect by SDS-PAGE. Total protein, amino
      acid composition and kernel texture were analyzed. CONCLUSIONS: The alpha-zeins
      were dramatically reduced, but the high total seed protein level remained
      unchanged by complementary increase of non-zein proteins. Moreover, the residual
      zein levels still allowed for a vitreous hard seed. Such dramatic rebalancing of
      the nitrogen sink could have a major impact in world food supply.

PMID- 22393456
TI  - Characterization of within-host Plasmodium falciparum diversity using next
      generation sequence data.
AB  - Our understanding of the composition of multi-clonal malarial infections and the
      epidemiological factors which shape their diversity remain poorly understood.
      Traditionally within-host diversity has been defined in terms of the multiplicity
      of infection (MOI) derived by PCR-based genotyping. Massively parallel, single
      molecule sequencing technologies now enable individual read counts to be derived
      on genome-wide datasets facilitating the development of new statistical
      approaches to describe within-host diversity. In this class of measures the F(WS)
      metric characterizes within-host diversity and its relationship to population
      level diversity. Utilizing P. falciparum field isolates from patients in West
      Africa we here explore the relationship between the traditional MOI and F(WS)
      approaches. F(WS) statistics were derived from read count data at 86,158 SNPs in
      64 samples sequenced on the Illumina GA platform. MOI estimates were derived by
      PCR at the msp-1 and -2 loci. Significant correlations were observed between the
      two measures, particularly with the msp-1 locus (P = 5.92*10(-5)). The F(WS)
      metric should be more robust than the PCR-based approach owing to reduced
      sensitivity to potential locus-specific artifacts. Furthermore the F(WS) metric
      captures information on a range of parameters which influence out-crossing risk
      including the number of clones (MOI), their relative proportions and genetic
      divergence. This approach should provide novel insights into the factors which
      correlate with, and shape within-host diversity.

PMID- 22393457
TI  - Beauty hinders attention switch in change detection: the role of facial
      attractiveness and distinctiveness.
AB  - BACKGROUND: Recent research has shown that the presence of a task-irrelevant
      attractive face can induce a transient diversion of attention from a perceptual
      task that requires covert deployment of attention to one of the two locations.
      However, it is not known whether this spontaneous appraisal for facial beauty
      also modulates attention in change detection among multiple locations, where a
      slower, and more controlled search process is simultaneously affected by the
      magnitude of a change and the facial distinctiveness. Using the flicker paradigm,
      this study examines how spontaneous appraisal for facial beauty affects the
      detection of identity change among multiple faces. METHODOLOGY/PRINCIPAL
      FINDINGS: Participants viewed a display consisting of two alternating frames of
      four faces separated by a blank frame. In half of the trials, one of the faces
      (target face) changed to a different person. The task of the participant was to
      indicate whether a change of face identity had occurred. The results showed that
      (1) observers were less efficient at detecting identity change among multiple
      attractive faces relative to unattractive faces when the target and distractor
      faces were not highly distinctive from one another; and (2) it is difficult to
      detect a change if the new face is similar to the old. CONCLUSIONS/SIGNIFICANCE:
      The findings suggest that attractive faces may interfere with the attention
      switch process in change detection. The results also show that attention in
      change detection was strongly modulated by physical similarity between the
      alternating faces. Although facial beauty is a powerful stimulus that has well
      demonstrated priority, its influence on change detection is easily superseded by
      low-level image similarity. The visual system appears to take a different
      approach to facial beauty when a task requires resource-demanding feature
      comparisons.

PMID- 22393458
TI  - Enhanced Notch activation is advantageous but not essential for T cell
      lymphomagenesis in Id1 transgenic mice.
AB  - T cell lymphoblastic leukemia (T-ALL) is known to be associated with chromosomal
      abnormalities that lead to aberrant expression of a number of transcription
      factors such as TAL1, which dimerizes with basic helix-loop-helix (bHLH) E
      proteins and inhibits their function. Activated Notch receptors also efficiently
      induce T cell leukemogenesis in mouse models. Interestingly, gain-of-function
      mutations or cryptic transcription initiation of the Notch1 gene have been
      frequently found in both human and mouse T-ALL. However, the correlations between
      these alterations and overall Notch activities or leukemogenesis have not been
      thoroughly evaluated. Therefore, we made use of our collection of T cell
      lymphomas developed in transgenic mice expressing Id1, which like TAL1, inhibits
      E protein function. By comparing expression levels of Notch target genes in Id1
      expressing tumors to those in tumors induced by a constitutively active form of
      Notch1, N1C, we were able to assess the overall activities of Notch pathways and
      conclude that the majority of Id1-expressing tumors had elevated Notch function
      to a varying degree. However, 26% of the Id1-expressing tumors had no evidence of
      enhanced Notch activation, but that did not delay the onset of tumorigenesis.
      Furthermore, we examined the genetic or epigenetic alterations thought to
      contribute to ligand-independent activation or protein stabilization of Notch1
      and found that some of the Id1-expressing tumors acquired these changes, but they
      are not uniformly associated with elevated Notch activities in Id1 tumor samples.
      In contrast, N1C-expressing tumors do not harbor any PEST domain mutations nor
      exhibit intragenic transcription initiation. Taken together, it appears that
      Notch activation provides Id1-expressing tumor cells with selective advantages in
      growth and survival. However, this may not be absolutely essential for
      lymphomagenesis in Id1 transgenic mice and additional factors could also
      cooperate with Id1 to induce T cell lymphoma. Therefore, a broad approach is
      necessary in designing T-ALL therapy.

PMID- 22393459
TI  - Perturbation of the hematopoietic system during embryonic liver development due
      to disruption of polyubiquitin gene Ubc in mice.
AB  - Disruption of the polyubiquitin gene Ubc leads to a defect in fetal liver
      development, which can be partially rescued by increasing the amount of
      ubiquitin. However, it is still not known why Ubc is required for fetal liver
      development and the nature of the defective cell types responsible for embryonic
      lethality have not been characterized. In this study, we assessed the cause of
      embryonic lethality with respect to the fetal liver hematopoietic system. We
      found that Ubc was highly expressed in the embryonic liver, and the proliferation
      capacity of fetal liver cells was reduced in Ubc(-/-) embryos. Specifically, Ubc
      was most highly expressed in hematopoietic cells, and the proliferation capacity
      of hematopoietic cells was significantly impaired in Ubc(-/-) embryos. While
      hematopoietic cell and hematopoietic stem cell (HSC) frequency was maintained in
      Ubc(-/-) embryos, the absolute number of these cells was diminished because of
      reduced total liver cell number in Ubc(-/-) embryos. Transplantations of fetal
      liver cells into lethally irradiated recipient mice by non-competitive and
      competitive reconstitution methods indicated that disruption of Ubc does not
      significantly impair the intrinsic function of fetal liver HSCs. These findings
      suggest that disruption of Ubc reduces the absolute number of HSCs in embryonic
      livers, but has no significant effect on the autonomous function of HSCs. Thus,
      the lethality of Ubc(-/-) embryos is not the result of intrinsic HSC failure.

PMID- 22393460
TI  - Porphyrins-Functionalized Single-Walled Carbon Nanotubes Chemiresistive Sensor
      Arrays for VOCs.
AB  - Single-walled carbon nanotubes (SWNTs) have been used extensively for sensor
      fabrication due to its high surface to volume ratio, nanosized structure and
      interesting electronic property. Lack of selectivity is a major limitation for
      SWNTs-based sensors. However, surface modification of SWNTs with a suitable
      molecular recognition system can enhance the sensitivity. On the other hand,
      porphyrins have been widely investigated as functional materials for chemical
      sensor fabrication due to their several unique and interesting physico-chemical
      properties. Structural differences between free-base and metal substituted
      porphyrins make them suitable for improving selectivity of sensors. However,
      their poor conductivity is an impediment in fabrication of prophyrin-based
      chemiresistor sensors. The present attempt is to resolve these issues by
      combining freebase- and metallo-porphyrins with SWNTs to fabricate SWNTs
      porphyrin hybrid chemiresistor sensor arrays for monitoring volatile organic
      carbons (VOCs) in air. Differences in sensing performance were noticed for
      porphyrin with different functional group and with different central metal atom.
      The mechanistic study for acetone sensing was done using field-effect transistor
      (FET) measurements and revealed that the sensing mechanism of ruthenium octaethyl
      porphyrin hybrid device was governed by electrostatic gating effect, whereas iron
      tetraphenyl porphyrin hybrid device was governed by electrostatic gating and
      Schottky barrier modulation in combination. Further, the recorded electronic
      responses for all hybrid sensors were analyzed using a pattern-recognition
      analysis tool. The pattern-recognition analysis confirmed a definite pattern in
      response for different hybrid material and could efficiently differentiate
      analytes from one another. This discriminating capability of the hybrid
      nanosensor devices open up the possibilities for further development of highly
      dense nanosensor array with suitable porphyrin for E-nose application.

PMID- 22393461
TI  - Eliminating rabies in Estonia.
AB  - The compulsory vaccination of pets, the recommended vaccination of farm animals
      in grazing areas and the extermination of stray animals did not succeed in
      eliminating rabies in Estonia because the virus was maintained in two main
      wildlife reservoirs, foxes and raccoon dogs. These two species became a priority
      target therefore in order to control rabies. Supported by the European Community,
      successive oral vaccination (OV) campaigns were conducted twice a year using
      Rabigen(r) SAG2 baits, beginning in autumn 2005 in North Estonia. They were then
      extended to the whole territory from spring 2006. Following the vaccination
      campaigns, the incidence of rabies cases dramatically decreased, with 266 cases
      in 2005, 114 in 2006, four in 2007 and three in 2008. Since March 2008, no rabies
      cases have been detected in Estonia other than three cases reported in summer
      2009 and one case in January 2011, all in areas close to the South-Eastern border
      with Russia. The bait uptake was satisfactory, with tetracycline positivity rates
      ranging from 85% to 93% in foxes and from 82% to 88% in raccoon dogs.
      Immunisation rates evaluated by ELISA ranged from 34% to 55% in foxes and from
      38% to 55% in raccoon dogs. The rabies situation in Estonia was compared to that
      of the other two Baltic States, Latvia and Lithuania. Despite regular OV
      campaigns conducted throughout their territory since 2006, and an improvement in
      the epidemiological situation, rabies has still not been eradicated in these
      countries. An analysis of the number of baits distributed and the funding
      allocated by the European Commission showed that the strategy for rabies control
      is more cost-effective in Estonia than in Latvia and Lithuania.

PMID- 22393462
TI  - CD44 Promotes Epithelial Mammary Gland Development and Exhibits Altered
      Localization during Cancer Progression.
AB  - The basal cell layer has emerged as a critical player in cancer progression, and
      understanding the molecular contribution of specific cell types is important in
      treatment and prevention. The adhesion receptor CD44, which mediates epithelial
      stromal and cell-cell interactions, has been shown to both promote and suppress
      tumor progression. To better understand the normal function of CD44, we have
      investigated its role in mouse mammary gland development and its expression in
      human breast and prostate cancer. We have found that CD44 is expressed in the
      myoepithelium of the developing mammary gland and modulates ductal development of
      FVB/N mice. The loss of CD44 results in defective luminal-myoepithelial cell-cell
      adhesion and promotes the mixing of luminal and myoepithelial layers, disrupting
      epithelial bilayer organization, and CD44-null mice experience delayed ductal
      outgrowth and impaired terminal end bud formation. The myoepithelial expression
      of CD44 is also relevant to its expression in cancer, as CD44 is expressed in the
      basal cells of early-stage breast and prostate cancer but exhibits altered
      localization with increasing tumorigenicity and is strongly expressed by tumor
      epithelium.

PMID- 22393463
TI  - Epigenetic Silencing of miR-203 Upregulates SNAI2 and Contributes to the
      Invasiveness of Malignant Breast Cancer Cells.
AB  - It has become increasingly clear that microRNAs (miRNAs) play important roles in
      tumorigenesis and metastasis. Recently, miR-203 was reported as a suppressor
      microRNA often silenced in different malignancies including hepatocellular
      carcinoma, prostate cancer, oral cancer, and hematopoietic malignancy, but little
      is known about its potential role in breast carcinogenesis. In this study, we
      found that in breast cancer, miR-203 was upregulated in primary tumors and some
      nonmetastatic cell lines but was significantly downregulated in metastatic cell
      lines including BT549, Hs578T, and MDA-MB-231, as measured by regular and real
      time PCR. Downregulation of miR-203 in metastatic breast cancer cells appeared to
      be caused by hypermethylation of its promoter. Functionally, ectopic expression
      of miR-203 in BT549 and MDA-MB-231 breast cancer cell lines caused cell cycle
      arrest and apoptosis and inhibited cell invasion and migration in vitro.
      Bioinformatic analysis predicted the snail homolog 2 (SNAI2 or SLUG), a
      transcription factor that promotes cell invasion and tumor metastasis, as a
      target of miR-203, and the prediction was validated by expression analysis and
      luciferase reporter assay of the 3' untranslated region of SNAI2 that contains
      the miR-203 target sequences. These results suggest that in malignant breast
      cancer cells, miR-203 is epigenetically silenced, and the silencing promotes
      tumor cell growth and invasion at least in part by upregulating the SNAI2
      transcription factor.

PMID- 22393464
TI  - ErbB2 Is Necessary for ErbB4 Ligands to Stimulate Oncogenic Activities in Models
      of Human Breast Cancer.
AB  - ErbB4 is a member of the ErbB family of receptor tyrosine kinases. This family
      includes ErbB2 (HER2/Neu), a validated therapeutic target in breast cancer.
      Several studies indicate that ErbB4 functions as a tumor suppressor in breast
      cancer, whereas others indicate that ErbB4 functions as an oncogene. Here the
      authors explore the context in which ErbB4 functions as an oncogene. Silencing
      expression of either ErbB2 or ErbB4 in breast tumor cell lines results in reduced
      stimulation of anchorage independence and cell motility by the ErbB4 agonist
      neuregulin 2beta. ErbB2 tyrosine kinase activity, but not ErbB4 tyrosine kinase
      activity, is required for neuregulin 2beta to stimulate cell proliferation.
      Moreover, sites of ErbB4 tyrosine phosphorylation, but not sites of ErbB2
      tyrosine phosphorylation, are required for neuregulin 2beta to couple to cell
      proliferation. These data suggest that targeting ErbB2 expression or tyrosine
      kinase activity may be effective in treating ErbB4-dependent breast tumors, even
      those tumors that lack ErbB2 overexpression.

PMID- 22393465
TI  - Identification of c-Myb Target Genes in K562 Cells Reveals a Role for c-Myb as a
      Master Regulator.
AB  - The c-Myb transcription factor is an important regulator of hematopoietic cell
      development. c-Myb is expressed in immature hematopoietic cells and plays a
      direct role in lineage fate selection, cell cycle progression, and
      differentiation of myeloid as well as B- and T-lymphoid progenitor cells. As a
      DNA-binding transcription factor, c-Myb regulates specific gene programs through
      activation of target genes. Still, our understanding of these programs is
      incomplete. Here, we report a set of novel c-Myb target genes, identified using a
      combined approach: specific c-Myb knockdown by 2 different siRNAs and subsequent
      global expression profiling, combined with the confirmation of direct binding of
      c-Myb to the target promoters by ChIP assays. The combination of these 2
      approaches, as well as additional validation such as cloning and testing the
      promoters in reporter assays, confirmed that MYADM, LMO2, GATA2, STAT5A, and
      IKZF1 are target genes of c-Myb. Additional studies, using chromosome
      conformation capture, demonstrated that c-Myb target genes may directly interact
      with each other, indicating that these genes may be coordinately regulated. Of
      the 5 novel target genes identified, 3 are transcription factors, and one is a
      transcriptional co-regulator, supporting a role of c-Myb as a master regulator
      controlling the expression of other transcriptional regulators in the
      hematopoietic system.

PMID- 22393466
TI  - AKT Activation by Pdcd4 Knockdown Up-Regulates Cyclin D1 Expression and Promotes
      Cell Proliferation.
AB  - Programmed cell death 4 (Pdcd4), a novel tumor suppressor, inhibits neoplastic
      transformation and tumor invasion. In this study, the authors found that
      knockdown of Pdcd4 promoted cell proliferation and up-regulated cyclin D1
      expression. Previously, the authors demonstrated that Pdcd4 knockdown activated
      NF-kappaB-dependent transcription. Mutations of NF-kappaB binding sites on the
      cyclin D1 promoter attenuated the cyclin D1 promoter activity induced by Pdcd4
      knockdown. In addition, knockdown of NF-kappaB/IkappaB kinase (IKK) alpha or
      IKKbeta, the kinase regulating NF-kappaB activation, inhibited cyclin D1 promoter
      activity and cyclin D1 expression, indicating that up-regulation of cyclin D1 by
      Pdcd4 knockdown is contributed, at least in part, by NF-kappaB activation. To
      investigate the mechanism of how Pdcd4 knockdown activates NF-kappaB, the authors
      found that the levels of AKT phosphorylation and AKT kinase activity were
      increased in the Pdcd4 knockdown cells. Conversely, ectopic expression of Pdcd4
      inhibited AKT phosphorylation and cyclin D1 expression, suggesting that Pdcd4
      regulates AKT activity and cyclin D1 expression. Furthermore, knockdown of AKT in
      the Pdcd4 knockdown cells inhibited IKK phosphorylation, NF-kappaB activation,
      cyclin D1 promoter activity, and cyclin D1 expression as well as cell
      proliferation. Taken together, these findings suggest that activation of NF
      kappaB by Pdcd4 knockdown through AKT contributes to the elevated expression of
      cyclin D1, thus providing new insights into how loss of Pdcd4 expression promotes
      tumor development.

PMID- 22393467
TI  - Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated
      Expression in Colorectal Adenomas and Adenocarcinomas.
AB  - An uncharacterized gene locus (Chr16:hCG_1815491), now named colorectal neoplasia
      differentially expressed (gene symbol CRNDE), is activated early in colorectal
      neoplasia. The locus is unrelated to any known protein-coding gene. Microarray
      analysis of 454 tissue specimens (discovery) and 68 previously untested specimens
      (validation) showed elevated expression of CRNDE in >90% of colorectal adenomas
      and adenocarcinomas. These findings were confirmed and extended by exon
      microarray studies and RT-PCR assays. CRNDE transcription start sites were
      identified in CaCo2 and HCT116 cells by 5'-RACE. The major transcript isoforms in
      colorectal cancer (CRC) cell lines and colorectal tissue are CRNDE-a, -b, -d, -e,
      -f, -h, and -j. Except for CRNDE-d, the known CRNDE splice variants are
      upregulated in neoplastic colorectal tissue; expression levels for CRNDE-h alone
      demonstrate a sensitivity of 95% and specificity of 96% for adenoma versus normal
      tissue. A quantitative RT-PCR assay measuring CRNDE-h RNA levels in plasma was
      (with a threshold of 2(-DeltaCt) = 2.8) positive for 13 of 15 CRC patients (87%)
      but only 1 of 15 healthy individuals (7%). We conclude that individual CRNDE
      transcripts show promise as tissue and plasma biomarkers, potentially exhibiting
      high sensitivity and specificity for colorectal adenomas and cancers.

PMID- 22393468
TI  - Protein kinase a-dependent phosphorylation of serine 119 in the proto-oncogenic
      serine/arginine-rich splicing factor 1 modulates its activity as a splicing
      enhancer protein.
AB  - Serine/arginine-rich splicing factor 1 (SRSF1), previously designated SF2/ASF,
      belongs to a family of SR proteins that regulate constitutive and alternative
      splicing. SRSF1 expression is increased in tumors from several tissues and
      elicits changes in key target genes involved in tumor genesis. Several protein
      kinases phosphorylate SRSF1, which regulates its localization and function. It is
      previously reported that protein kinase A (PKA) phosphorylates SRSF1, but the
      importance of this modification is not well characterized. Here, we show that PKA
      phosphorylates SRSF1 on serine 119 in vitro. Phosphorylation of SRSF1 on this
      site enhanced the RNA binding capacity of SRSF1 in vivo and reduced the protein's
      capacity to activate splicing of the Minx transcript in vitro. We also confirm an
      interaction between SRSF1 and PKA Calpha1 and demonstrate that this interaction
      is not dependent on serine 119 phosphorylation but requires active PKA Calpha1.
      We conclude that PKA phosphorylation of SRSF1 at serine 119 regulates SFRS1
      dependent RNA binding and processing but not its interaction with PKA.

PMID- 22393469
TI  - Jobs encompassing prolonged sitting in cramped positions and risk of venous
      thromboembolism: cohort study.
AB  - OBJECTIVES: There is mounting evidence that prolonged cramped sitting in
      connection with long-lasting air travel increases the risk of deep vein
      thrombosis of the legs and pulmonary embolism, i.e. venous thromboembolism (VTE).
      Prolonged cramped sitting may occur even in various jobs unrelated to air travel,
      and, theoretically, be associated with an increased risk of VTE. The issue is
      unsettled. DESIGN: A dynamic cohort study (open for both entry and departure) in
      Danish national registers 1997-2006. PARTICIPANTS: 20-59-year-old manual workers.
      The cohort consisted of an exposed group with job functions basically
      characterised as sedentary (n = 105,564) and a control group with more dynamic
      work (n = 283,966). SETTING: Denmark. MAIN OUTCOME MEASURES: Deaths and hospital
      contacts due to pulmonary embolism and deep vein thrombosis. RESULTS: Compared
      with occupations characterized by dynamic physical activity, the group
      encompassing those who would potentially be exposed to prolonged sitting in
      ergonomically adverse positions, had a significantly higher risk of pulmonary
      embolism (n = 77, relative risk 1.28; 95% CI 0.97-1.67, P = 0.04 in one-sided
      test). With respect to deep vein thrombosis they had a slightly but not
      significantly higher risk (n = 256, relative risk 1.09; 95% CI 0.94-1.26, P =
      0.12). CONCLUSION: Despite the crude method used allowing for no control of
      individual risk factors, occupations encompassing longer and shorter periods of
      sitting in potentially adverse ergonomic positions, i.e. cramped sitting, had a
      higher risk of VTE, than a socioeconomically comparable group with more dynamic
      physical work demands.

PMID- 22393470
TI  - Giant retroperitoneal liposarcoma.

PMID- 22393471
TI  - Co-existence of Crohn's disease, sarcoidosis and malignant lymphomas.

PMID- 22393472
TI  - Subcutaneous haematomas following thrombolysis treatment for ischaemic stroke.

PMID- 22393473
TI  - Health-related quality of life in Cystic Fibrosis patients infected with
      transmissible Pseudomonas aeruginosa strains: cohort study.
AB  - OBJECTIVES: To assess the impact on health-related quality of life (HRQoL) in
      adult cystic fibrosis (CF) patients of chronic infection with the Liverpool
      Epidemic Strain (LES) of Pseudomonas aeruginosa (Psa). DESIGN: Cohort study.
      PARTICIPANTS: Adult CF patients attending a single CF centre. SETTING: Outpatient
      clinic. MAIN OUTCOME MEASURES: HRQoL measures of adult CF patients chronically
      infected with LES and Psa strains measured by CFQ-UK. RESULTS: Patients infected
      by transmissible Psa strains had worse physical functioning, respiratory
      symptoms, treatment burden, vitality, role, health perception and emotion than
      those with unique Psa strains (P < 0.01), and significantly poorer physical
      functioning, respiratory symptoms, treatment burden, body image, weight, role,
      and emotion than those without any Psa infection (P < 0.05). Furthermore, in a
      matched cohort of 39 patients, those with LES infection reported significantly
      worse physical functioning, treatment burden, respiratory symptoms and health
      perception than those with unique Psa infection (P < 0.02). CONCLUSION: Chronic
      infection with transmissible Psa strains, particularly LES, confers a worse
      quality of life in adult CF patients. Coupled with the established poorer
      clinical outcome, this reinforces the need to prevent the spread of such strains
      in CF community.

PMID- 22393474
TI  - Successful myomectomy of a bleeding myoma in a twin pregnancy.

PMID- 22393475
TI  - A novel cytofluorometric assay for the detection and quantification of glucose-6
      phosphate dehydrogenase deficiency.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy
      that affects hundreds of millions of people worldwide, conferring increased risk
      of neonatal jaundice and oxidant-induced hemolytic anemia. Screening and
      diagnosis of G6PD deficiency is currently performed using genetic or biochemical
      assays, the former being cost ineffective in populations with significant allelic
      heterogeneity, and the latter being limited in ability to detect female
      heterozygotes. Cytochemical assays can obviate these shortcomings, but at the
      expense of added technical complexity and labor. We describe here a simple, novel
      cytofluorometric method that extends the classic methemoglobin reduction test,
      assessing G6PD deficiency at the level of an individual erythrocyte. In
      preliminary testing in Malian children, there was strong concordance between our
      method and established genetic and biochemical techniques. The assay is robust
      and economical, and could serve as a screening method as well as a research tool,
      especially for high-throughput applications such as flow cytometry.

PMID- 22393476
TI  - Reduced sampling efficiency causes degraded Vernier hyperacuity with normal
      aging: Vernier acuity in position noise.
AB  - Vernier acuity, a form of visual hyperacuity, is amongst the most precise forms
      of spatial vision. Under optimal conditions Vernier thresholds are much finer
      than the inter-photoreceptor distance. Achievement of such high precision is
      based substantially on cortical computations, most likely in the primary visual
      cortex. Using stimuli with added positional noise, we show that Vernier
      processing is reduced with advancing age across a wide range of noise levels.
      Using an ideal observer model, we are able to characterize the mechanisms
      underlying age-related loss, and show that the reduction in Vernier acuity can be
      mainly attributed to the reduction in efficiency of sampling, with no significant
      change in the level of internal position noise, or spatial distortion, in the
      visual system.

PMID- 22393478
TI  - Natural selection on body size is mediated by multiple interacting factors: a
      comparison of beetle populations varying naturally and experimentally in body
      size.
AB  - Body size varies considerably among species and among populations within species,
      exhibiting many repeatable patterns. However, which sources of selection generate
      geographic patterns, and which components of fitness mediate evolution of body
      size, are not well understood. For many animals, resource quality and
      intraspecific competition may mediate selection on body size producing large
      scale geographic patterns. In two sequential experiments, we examine how
      variation in larval competition and resource quality (seed size) affects the
      fitness consequences of variation in body size in a scramble-competing seed
      feeding beetle, Stator limbatus. Specifically, we compared fitness components
      among three natural populations of S. limbatus that vary in body size, and then
      among three lineages of beetles derived from a single base population
      artificially selected to vary in size, all reared on three sizes of seeds at
      variable larval density. The effects of larval competition and seed size on
      larval survival and development time were similar for larger versus smaller
      beetles. However, larger-bodied beetles suffered a greater reduction in adult
      body mass with decreasing seed size and increasing larval density; the relative
      advantage of being large decreased with decreasing seed size and increasing
      larval density. There were highly significant interactions between the effects of
      seed size and larval density on body size, and a significant three-way
      interaction (population-by-density-by-seed size), indicating that environmental
      effects on the fitness consequences of being large are nonadditive. Our study
      demonstrates how multiple ecological variables (resource availability and
      resource competition) interact to affect organismal fitness components, and that
      such interactions can mediate natural selection on body size. Studying individual
      factors influencing selection on body size may lead to misleading results given
      the potential for nonlinear interactions among selective agents.

PMID- 22393479
TI  - Evolution and plasticity of anuran larval development in response to desiccation.
      A comparative analysis.
AB  - Anurans breed in a variety of aquatic habitats with contrasting levels of
      desiccation risk, which may result in selection for faster development during
      larval stages. Previous studies suggest that species in ephemeral ponds reduce
      their developmental times to minimize desiccation risks, although it is not clear
      how variation in desiccation risk affects developmental strategies in different
      species. Employing a comparative phylogenetic approach including data from
      published and unpublished studies encompassing 62 observations across 30 species,
      we tested if species breeding in ephemeral ponds (High risk) develop faster than
      those from permanent ponds (Low risk) and/or show increased developmental
      plasticity in response to drying conditions. Our analyses support shorter
      developmental times in High risk, primarily by decreasing body mass at
      metamorphosis. Plasticity in developmental times was small and did not differ
      between groups. However, accelerated development in High risk species generally
      resulted in reduced sizes at metamorphosis, while some Low risk species were able
      compensate this effect by increasing mean growth rates. Taken together, our
      results suggest that plastic responses in species breeding in ephemeral ponds are
      constrained by a general trade-off between development and growth rates.

PMID- 22393477
TI  - The role of GRK6 in animal models of Parkinson's disease and L-DOPA treatment.
AB  - G protein-coupled Receptor Kinase 6 (GRK6) belongs to a family of kinases that
      phosphorylate GPCRs. GRK6 levels were found to be altered in Parkinson's Disease
      (PD) and D(2) dopamine receptors are supersensitive in mice lacking GRK6 (GRK6-KO
      mice). To understand how GRK6 modulates the behavioral manifestations of dopamine
      deficiency and responses to L-DOPA, we used three approaches to model PD in GRK6
      KO mice: 1) the cataleptic response to haloperidol; 2) introducing GRK6 mutation
      to an acute model of absolute dopamine deficiency, DDD mice; 3) hemiparkinsonian
      6-OHDA model. Furthermore, dopamine-related striatal signaling was analyzed by
      assessing the phosphorylation of AKT/GSK3beta and ERK1/2. GRK6 deficiency reduced
      cataleptic behavior, potentiated the acute effect of L-DOPA in DDD mice, reduced
      rotational behavior in hemi-parkinsonian mice, and reduced abnormal involuntary
      movements induced by chronic L-DOPA. These data indicate that approaches to
      regulate GRK6 activity could be useful in modulating both therapeutic and side
      effects of L-DOPA.

PMID- 22393480
TI  - Population delimitation across contrasting evolutionary clines in deer mice
      (Peromyscus maniculatus).
AB  - Despite current interest in population genetics, a concrete definition of a
      "population" remains elusive. Multiple ecologically and evolutionarily based
      definitions of population are in current use, which focus, respectively, on
      demographic and genetic interactions. Accurate population delimitation is crucial
      for not only evolutionary and ecological population biology, but also for
      conservation of threatened populations. Along the Pacific Coast of North America,
      two contrasting patterns of geographic variation in deer mice (Peromyscus
      maniculatus) converge within the state of Oregon. Populations of these mice
      diverge morphologically across an east-west axis, and they diverge in
      mitochondrial DNA haplotypes across a north-south axis. In this study, we
      investigate these geographically contrasting patterns of differentiation in the
      context of ecological and evolutionary definitions (paradigms) of populations. We
      investigate these patterns using a new and geographically expansive sample that
      integrates data on morphology, mitochondrial DNA, and nuclear DNA. We found no
      evidence of nuclear genetic differentiation between the morphologically and
      mitochondrially distinct populations, thus indicating the occurrence of gene flow
      across Oregon. Under the evolutionary paradigm, Oregon populations can be
      considered a single population, whereas morphological and mitochondrial
      differentiations do not indicate distinct populations. In contrast, under the
      ecological paradigm morphological differentiation indicates distinct populations
      based on the low likelihood of demographic interactions between geographically
      distant individuals. The two sympatric but mitochondrially distinct haplogroups
      form a single population under the ecological paradigm. Hence, we find that the
      difference between evolutionary and ecological paradigms is the time-scale of
      interest, and we believe that the more chronologically inclusive evolutionary
      paradigm may be preferable except in cases where only a single generation is of
      interest.

PMID- 22393481
TI  - Oosorption in response to poor food: complexity in the trade-off between
      reproduction and survival.
AB  - Plasticity in reproductive physiology is one avenue by which environmental
      signals, such as poor quality food, can be coordinated with adaptive responses.
      Insects have the ability to resorb oocytes that are not oviposited. Oosorption is
      proposed to be an adaptive mechanism to optimize fitness in hostile environments,
      recouping resources that might otherwise be lost, and reinvesting them into
      future reproductive potential. We tested the hypothesis that oosorption is an
      evolved mechanism by which females can reallocate resources from current
      reproductive effort to survival and future reproduction, when conditions for
      reproduction are poor, by examining the reproductive physiology and life-history
      outcome under poor quality food in populations of the milkweed bug (Oncopeltus
      fasciatus) that have adapted to live on sunflower seed. Females fed a diet of
      pumpkin seeds, known to be a poor host food, had higher levels of ovarian
      apoptosis (oosorption), lower reproductive output, but no reduction in life span
      under poor nutrition, as predicted under the oosorption hypothesis. However, the
      schedule of reproduction was surprising given the "wait to reproduce" assumption
      of oosorption as early fecundity was unaffected.

PMID- 22393482
TI  - Phylogeography of the ant Myrmica rubra and its inquiline social parasite.
AB  - Widely distributed Palearctic insects are ideal to study phylogeographic patterns
      owing to their high potential to survive in many Pleistocene refugia and-after
      the glaciation-to recolonize vast, continuous areas. Nevertheless, such species
      have received little phylogeographic attention. Here, we investigated the
      Pleistocene refugia and subsequent postglacial colonization of the common,
      abundant, and widely distributed ant Myrmica rubra over most of its Palearctic
      area, using mitochondrial DNA (mtDNA). The western and eastern populations of M.
      rubra belonged predominantly to separate haplogroups, which formed a broad
      secondary contact zone in Central Europe. The distribution of genetic diversity
      and haplogroups implied that M. rubra survived the last glaciation in multiple
      refugia located over an extensive area from Iberia in the west to Siberia in the
      east, and colonized its present areas of distribution along several routes. The
      matrilineal genetic structure of M. rubra was probably formed during the last
      glaciation and subsequent postglacial expansion. Additionally, because M. rubra
      has two queen morphs, the obligately socially parasitic microgyne and its
      macrogyne host, we tested the suggested speciation of the parasite. Locally, the
      parasite and host usually belonged to the same haplogroup but differed in
      haplotype frequencies. This indicates that genetic differentiation between the
      morphs is a universal pattern and thus incipient, sympatric speciation of the
      parasite from its host is possible. If speciation is taking place, however, it is
      not yet visible as lineage sorting of the mtDNA between the morphs.

PMID- 22393483
TI  - Criteria for assessing climate change impacts on ecosystems.
AB  - There is concern about the potential impacts of climate change on species and
      ecosystems. To address this concern, a large body of literature has developed in
      which these impacts are assessed. In this study, criteria for conducting reliable
      and useful assessments of impacts of future climate are suggested. The major
      decisions involve: clearly defining an emissions scenario; selecting a climate
      model; evaluating climate model skill and bias; quantifying General Circulation
      Model (GCM) between-model variability; selecting an ecosystem model and assessing
      uncertainty; properly considering transient versus equilibrium responses;
      including effects of CO(2) on plant response; evaluating implications of
      simplifying assumptions; and considering animal linkage with vegetation. A sample
      of the literature was surveyed in light of these criteria. Many of the studies
      used climate simulations that were >10 years old and not representative of best
      current models. Future effects of elevated CO(2) on plant drought resistance and
      productivity were generally included in growth model studies but not in niche
      (habitat suitability) studies, causing the latter to forecast greater future
      adverse impacts. Overly simplified spatial representation was frequent and caused
      the existence of refugia to be underestimated. Few studies compared multiple
      climate simulations and ecosystem models (including parametric uncertainty),
      leading to a false impression of precision and potentially arbitrary results due
      to high between-model variance. No study assessed climate model retrodictive
      skill or bias. Overall, most current studies fail to meet all of the proposed
      criteria. Suggestions for improving assessments are provided.

PMID- 22393484
TI  - Small founding number and low genetic diversity in an introduced species
      exhibiting limited invasion success (speckled dace, Rhinichthys osculus).
AB  - Molecular evaluations of successful invaders are common, however studies of
      introduced species that have had limited invasion success, or have died out
      completely, are rare. We studied an introduced population of speckled dace
      (Rhinichthys osculus) from northern California, USA that has rapidly increased in
      abundance but remained restricted to a 25-km stretch of river since its
      introduction in the mid-1980s. Field and laboratory analyses indicate that
      invasion success of speckled dace is constrained by the combined effects of
      multiple predators. The role of bottleneck effects associated with the
      introduction has not been studied. We assayed variation in seven microsatellite
      loci and one mitochondrial DNA gene in the introduced population and nine
      putative source populations to identify the source population and evaluate
      bottleneck effects. The Trinity River system was supported as the source owing to
      its genetic similarity and geographic proximity to the introduced population.
      Consistent with a bottleneck, the introduced population exhibited reduced allelic
      and haplotype richness in comparison to source populations. Estimates of the
      genetically effective number of individuals founding the introduced population
      using nuclear coalescent analyses and a mitochondrial simulation procedure were
      highly concordant in suggesting that the initial colonizing group was comprised
      of about 10 individuals. A bottleneck effect in an exotic species exhibiting
      limited invasion success has rarely been documented and thus introduction of
      speckled dace represents an important model system for future investigation.
      Establishing a relationship between genetic diversity and factors limiting
      invasion success in this system (e.g., predator avoidance) will help determine
      the extent to which genetic diversity loss has constrained invasion success in
      speckled dace.

PMID- 22393485
TI  - Invasion of dwarf bamboo into alpine snow-meadows in northern Japan: pattern of
      expansion and impact on species diversity.
AB  - Recently, a dwarf bamboo species,Sasa kurilensis; Poaceae, has invaded into
      alpine snow-meadows in the wilderness area of the Taisetsu Mountains, northern
      Japan. This dwarf bamboo species has a wide distribution range from lowland to
      alpine sites of snowy regions. Because of the formation of dense evergreen culms
      and an extensive rhizome system, other plants are excluded following invasion by
      this dwarf bamboo, resulting in low species diversity. Dwarf bamboo originally
      inhabited the leeward slopes of alpine dwarf pine (Pinus pumila) clumps in alpine
      regions. During the last 32 years, however, dwarf bamboo has expanded its
      distribution area by up to 47% toward snow-meadows, especially on southeastern
      facing slopes. This rapid change may be related to the decrease in soil moisture
      and expansion of the annual growing period caused by the recent acceleration of
      snowmelt time. A multiyear census revealed that the density of bamboo culms
      increased 30-150% during 2 years, and the annual expansion of bamboo rhizomes was
      39 cm on average. In addition to the expansion of bamboo clumps by vegetative
      growth, the possibility of migration by seed dispersal was also suggested by a
      genet analysis. With the increase in culm density, the species richness of snow
      meadow vegetation decreased to less than one-quarter of the original level due to
      intense shading by dwarf bamboo. The rapid vegetation change in these almost
      pristine alpine environments isolated from the human activity implies that global
      climate change already influences the alpine ecosystem.

PMID- 22393487
TI  - Open debate and progress in ecology and evolution.

PMID- 22393486
TI  - Macroscale evolutionary patterns of flight muscle dimorphism in the carrion
      beetle Necrophila japonica.
AB  - Some insect species exhibit polymorphisms in flight muscles or wings, which
      provide opportunities for studying the factors that drive dispersal polymorphisms
      and the evolution of flightlessness in insects. We investigated the macroscale
      evolutionary pattern of flightlessness in the widespread Japanese beetle
      Necrophila japonica (Coleoptera: Silphidae), which exhibits flight muscle
      dimorphisms using phylogeographic approaches. N. japonica lives in both stable
      and unstable habitats, and the flight muscle dimorphisms may have been maintained
      through the use of these diverse habitats. We studied the distribution pattern of
      the proportion of individuals lacking flight muscles in relation to the genetic
      differentiation among geographic populations using an 842-base pair sequence of
      the COI-II gene. Both flight-capable and flightless individuals occurred over the
      distribution area, and the flight muscle condition showed no significant
      phylogeographic pattern. Several populations comprised flight-capable individuals
      only, whereas few comprised flightless ones only. Demographic expansion was
      suggested for major clades of COI-II haplotypes, and the genetic differentiation
      showed an isolation-by-distance pattern among the populations in Japan. The
      proportion of flightless individuals was higher in a population with a higher
      annual mean temperature and with higher genetic diversity among individuals.
      These results indicate that geographic expansion occurred recently while flight
      muscle dimorphisms have been maintained, that flight-capable individuals have
      colonized cooler (peripheral) habitats, and that flightlessness has increased in
      long-persisting populations as suggested by high genetic diversity.

PMID- 22393488
TI  - Spatial-genetic structuring in a red-breasted merganser (Mergus serrator) colony
      in the Canadian Maritimes.
AB  - The clustering of kin is widespread across the animal kingdom and two of the
      primary mechanisms underlying the formation of these patterns in adult kin are
      (1) philopatric tendencies and (2) actively maintained kin associations. Using
      polymorphic microsatellites, we had set out to characterize the level of genetic
      spatial organization within a colony of female red-breasted mergansers (Mergus
      serrator) breeding on a series of small barrier islands in Kouchibouguac National
      Park, NB, Canada. Additionally, using nesting data from this colony, we explored
      possibilities for the existence of kin associations and/or cooperative
      interactions between these individuals; specifically in the form of the
      synchronization of breeding activities (i.e., incubation initiation). Our results
      include: (1) the detection of broad-scale genetic structuring over the entire
      colony, as females nesting on separate islands were to some extent genetically
      distinct; (2) the detection of weak, yet significant, positive spatial
      autocorrelation of kin at the fine scale, but only in the more densely-populated
      areas of this colony; and (3) the synchrony of breeding activities among
      proximally nesting females, apart from any factors of relatedness. While these
      results confirm the existence of genetic-spatial organization within this colony,
      the underlying mechanisms producing such a signal are inconclusive.

PMID- 22393489
TI  - Life-history traits maintain the genomic integrity of sympatric species of the
      spruce budworm (Choristoneura fumiferana) group on an isolated forest island.
AB  - Identification of widespread species collected from islands can be challenging
      due to the potential for local ecological and phenotypic divergence in isolated
      populations. We sought to determine how many species of the spruce budworm
      (Choristoneura fumiferana) complex reside in Cypress Hills, an isolated remnant
      coniferous forest in western Canada. We integrated data on behavior, ecology,
      morphology, mitochondrial DNA, and simple sequence repeats, comparing Cypress
      Hills populations to those from other regions of North America to determine which
      species they resembled most. We identified C. fumiferana, C. occidentalis, C.
      lambertiana, and hybrid forms in Cypress Hills. Adult flight phenology and
      pheromone attraction were identified as key life-history traits involved in
      maintaining the genomic integrity of species. Our study highlights the importance
      of extensive sampling of both specimens and a variety of characters for
      understanding species boundaries in biodiversity research.

PMID- 22393490
TI  - Ungulate preference for burned patches reveals strength of fire-grazing
      interaction.
AB  - The interactions between fire and grazing are widespread throughout fire
      dependent landscapes. The utilization of burned areas by grazing animals
      establishes the fire-grazing interaction, but the preference for recently burned
      areas relative to other influences (water, topography, etc.) is unknown. In this
      study, we determine the strength of the fire-grazing interaction by quantifying
      the influence of fire on ungulate site selection. We compare the preference for
      recently burned patches relative to the influence of other environmental factors
      that contribute to site selection; compare that preference between native and
      introduced ungulates; test relationships between area burned and herbivore
      preference; and determine forage quality and quantity as mechanisms of site
      selection. We used two large ungulate species at two grassland locations within
      the southern Great Plains, USA. At each location, spatially distinct patches were
      burned within larger areas through time, allowing animals to select among burned
      and unburned areas. Using fine scale ungulate location data, we estimated
      resource selection functions to examine environmental factors in site selection.
      Ungulates preferred recently burned areas and avoided areas with greater time
      since fire, regardless of the size of landscape, herbivore species, or proportion
      of area burned. Forage quality was inversely related to time since fire, while
      forage quantity was positively related. We show that fire is an important
      component of large ungulate behavior with a strong influence on site selection
      that drives the fire-grazing interaction. This interaction is an ecosystem
      process that supersedes fire and grazing as separate factors, shaping grassland
      landscapes. Inclusion of the fire-grazing interaction into ecological studies and
      conservation practices of fire-prone systems will aid in better understanding and
      managing these systems.

PMID- 22393491
TI  - Variation in MHC genotypes in two populations of house sparrow (Passer
      domesticus) with different population histories.
AB  - Small populations are likely to have a low genetic ability for disease resistance
      due to loss of genetic variation through inbreeding and genetic drift. In
      vertebrates, the highest genetic diversity of the immune system is located at
      genes within the major histocompatibility complex (MHC). Interestingly, parasite
      mediated selection is thought to potentially maintain variation at MHC loci even
      in populations that are monomorphic at other loci. Therefore, general loss of
      genetic variation in the genome may not necessarily be associated with low
      variation at MHC loci. We evaluated inter- and intrapopulation variation in MHC
      genotypes between an inbred (Aldra) and a relatively outbred population
      (Hestmannoy) of house sparrows (Passer domesticus) in a metapopulation at
      Helgeland, Norway. Genomic (gDNA) and transcribed (cDNA) alleles of functional
      MHC class I and IIB loci, along with neutral noncoding microsatellite markers,
      were analyzed to obtain relevant estimates of genetic variation. We found lower
      allelic richness in microsatellites in the inbred population, but high genetic
      variation in MHC class I and IIB loci in both populations. This suggests that
      also the inbred population could be under balancing selection to maintain genetic
      variation for pathogen resistance.

PMID- 22393492
TI  - Adaptation to a seasonally varying environment: a strong latitudinal cline in
      reproductive diapause combined with high gene flow in Drosophila montana.
AB  - Adaptation to seasonal changes in the northern hemisphere includes an ability to
      predict the forthcoming cold season from gradual changes in environmental cues
      early enough to prepare for the harsh winter conditions. The magnitude and speed
      of changes in these cues vary between the latitudes, which induces strong
      selection pressures for local adaptation.We studied adaptation to seasonal
      changes in Drosophila montana, a northern maltfly, by defining the photoperiodic
      conditions leading to adult reproductive diapause along a latitudinal cline in
      Finland and by measuring genetic differentiation and the amount of gene flow
      between the sampling sites with microsatellites. Our data revealed a clear
      correlation between the latitude and the critical day length (CDL), in which half
      of the females of different cline populations enter photoperiodic reproductive
      diapause. There was no sign of limited gene flow between the cline populations,
      even though these populations showed isolation by distance. Our results show that
      local adaptation may occur even in the presence of high gene flow, when selection
      for locally adaptive life-history traits is strong. A wide range of variation in
      the CDLs of the fly strains within and between the cline populations may be
      partly due to gene flow and partly due to the opposing selection pressures for
      fly reproduction and overwinter survival. This variation in the timing of
      diapause will enhance populations' survival over the years that differ in the
      severity of the winter and in the length of the warm period and may also help
      them respond to long-term changes in environmental conditions.

PMID- 22393493
TI  - Comparison of population-genetic structuring in congeneric kelp- versus rock
      associated snails: a test of a dispersal-by-rafting hypothesis.
AB  - Phylogeographic studies indicate that many marine invertebrates lacking
      autonomous dispersal ability are able to achieve trans-oceanic colonization by
      rafting on buoyant macroalgae. However, less is known about the impact of rafting
      on on-going population-genetic connectivity of intertidal species associated with
      buoyant macroalgae. We hypothesize that such species will have higher levels of
      population-genetic connectivity than those exploiting nonbuoyant substrates such
      as rock. We tested this hypothesis by comparing nuclear multilocus population
      genetic structuring in two sister topshell species, which both have a planktonic
      larval phase but are fairly well segregated by their habitat preference of low
      tidal bull-kelp holdfasts versus mid-to-low tidal bare rock. We analyzed
      population samples from four sympatric sites spanning 372 km of the east coast of
      southern New Zealand. The sampled region encompasses a 180 km wide habitat
      discontinuity and is influenced by a stable, northward coastal current. The level
      of connectivity was high in both species, and neither of them showed significant
      correlation between genetic and geographic distances. However, a significant
      negative partial correlation between genetic distance and habitat discontinuity
      was found in the rock-associated species, and estimates of migrant movement
      between sites were somewhat different between the two species, with the kelp
      associated species more often yielding higher estimates across the habitat
      discontinuity, whereas the rock-associated species more often exhibited higher
      estimates between sites interspersed by rock habitats. We conclude that for
      species with substantial means of autonomous dispersal, the most conspicuous
      consequence of kelp dwelling may be enhanced long-distance dispersal across
      habitat discontinuities rather than a general increase of gene flow.

PMID- 22393494
TI  - Multimodal dispersal during the range expansion of the tropical house gecko
      Hemidactylus mabouia.
AB  - Dispersal influences both the ecological and evolutionary dynamics of range
      expansion. While some studies have demonstrated a role for human-mediated
      dispersal during invasion, the genetic effects of such dispersal remain to be
      understood, particularly in terrestrial range expansions. In this study, we
      investigated multimodal dispersal during the range expansion of the invasive
      gecko Hemidactylus mabouia in Florida using 12 microsatellite loci. We
      investigated dispersal patterns at the regional scale (metropolitan areas),
      statewide scale (state of Florida), and global scale (including samples from the
      native range). Dispersal was limited at the smallest, regional scale, within
      metropolitan areas, as reflected by the presence of genetic structure at this
      scale, which is in agreement with a previous study in this same invasion at even
      smaller spatial scales. Surprisingly, there was no detectable genetic structure
      at the intermediate statewide scale, which suggests dispersal is not limited
      across the state of Florida. There was evidence of genetic differentiation
      between Florida and other areas where H. mabouia occurs, so we concluded that at
      the largest scale, dispersal was limited. Humans likely contributed to patterns
      of dispersal at all three scales but in different ways. Infrequent low-volume
      dispersal has occurred within regions, frequent high-volume dispersal has
      occurred across the state, and infrequent long-distance dispersal has occurred
      among continents at the global scale. This study highlights the importance of
      considering different modes of dispersal at multiple spatial scales to understand
      the dynamics of invasion and range expansion.

PMID- 22393495
TI  - Post-Pleistocene range expansion of the recently imperiled eastern little brown
      bat (Myotis lucifugus lucifugus) from a single southern refugium.
AB  - Myotis lucifugus, once among the most widespread and common bats in North
      America, has been forecast to be extirpated east of the Rockies in as few as 16
      years by the spread of white-nose syndrome. Recent genetic research has
      demonstrated that this species is paraphyletic and part of a broader species
      complex; however, only one lineage (Myotis lucifugus lucifugus [M. l. lucifugus])
      is present in eastern North America. I used molecular tools and niche modeling to
      validate this and investigate the role that historical biogeography has played in
      the phylogenetic and population genetic structure of this species to determine if
      the eastern subspecies represents an evolutionarily distinct population.To
      establish the genetic structure within M. l. lucifugus, I densely sampled
      maternity colonies in Minnesota and sequenced 182 individuals for a portion of
      cytochrome b. Phylogenetic reconstruction and a haplotype network were used to
      infer the relationships among mitochondrial haplotypes. Population growth
      statistics were calculated to determine if there was evidence of significant
      expansion, and an environmental niche model (ENM) was constructed based on
      conditions during the last glacial maximum (LGM) to illustrate potential glacial
      refugia. All individuals derived from a single mitochondrial lineage. Genetic
      evidence points to population growth starting approximately 18 kya. ENM results
      show that there was likely a single large southern refugium extending across the
      southeastern United States and possibly several isolated refugia in western North
      America. Myotis lucifugus lucifugus likely maintained both a large range and a
      large population during the peaks of the glacial cycles, and its population
      appears to have expanded following the retreat of the Laurentide ice sheet. This
      imperiled lineage likely diverged in isolation from other members of the M.
      lucifugus/western long-eared Myotis during the Pleistocene.

PMID- 22393496
TI  - The habitat disruption induces immune-suppression and oxidative stress in honey
      bees.
AB  - The honey bee is a major insect used for pollination of many commercial crops
      worldwide. Although the use of honey bees for pollination can disrupt the
      habitat, the effects on their physiology have never been determined. Recently,
      honey bee colonies have often collapsed when introduced in greenhouses for
      pollination in Japan. Thus, suppressing colony collapses and maintaining the
      number of worker bees in the colonies is essential for successful long-term
      pollination in greenhouses and recycling of honey bee colonies. To understand the
      physiological states of honey bees used for long-term pollination in greenhouses,
      we characterized their gene expression profiles by microarray. We found that the
      greenhouse environment changes the gene expression profiles and induces immune
      suppression and oxidative stress in honey bees. In fact, the increase of the
      number of Nosema microsporidia and protein carbonyl content was observed in honey
      bees during pollination in greenhouses. Thus, honey bee colonies are likely to
      collapse during pollination in greenhouses when heavily infested with pathogens.
      Degradation of honey bee habitat by changing the outside environment of the
      colony, during pollination services for example, imposes negative impacts on
      honey bees. Thus, worldwide use of honey bees for crop pollination in general
      could be one of reasons for the decline of managed honey bee colonies.

PMID- 22393497
TI  - Genetic Connectivity among Populations of an Endangered Snake Species from
      Southeastern Australia (Hoplocephalus bungaroides, Elapidae).
AB  - For endangered species that persist as apparently isolated populations within a
      previously more extensive range, the degree of genetic exchange between those
      populations is critical to conservation and management. A lack of gene flow can
      exacerbate impacts of threatening processes and delay or prevent colonization of
      sites after local extirpation. The broad-headed snake, Hoplocephalus bungaroides,
      is a small venomous species restricted to a handful of disjunct reserves near
      Sydney, Australia. Mark-recapture studies have indicated low vagility for this
      ambush predator, suggesting that gene flow also may be low. However, our analyses
      of 11 microsatellite loci from 163 snakes collected in Morton National Park, from
      six sites within a 10-km diameter, suggest relatively high rates of gene flow
      among sites. Most populations exchange genes with each other, with one large
      population serving as a source area and smaller populations apparently acting as
      sinks. About half of the juvenile snakes, for which we could reliably infer
      parentage, were collected from populations other than those in which we collected
      their putative parents. As expected from the snakes' reliance on rocky outcrops
      during cooler months of the year, most gene flow appears to be along sandstone
      plateaux rather than across the densely forested valleys that separate plateaux.
      The unexpectedly high rates of gene flow on a landscape scale are encouraging for
      future conservation of this endangered taxon. For example, wildlife managers
      could conserve broad-headed snakes by restoring habitats near extant source
      populations in areas predicted to be least affected by future climate change.

PMID- 22393499
TI  - Community assembly and diversification in Indo-Pacific coral reef fishes.
AB  - Theories of species coexistence have played a central role in ecology and
      evolutionary studies of the origin and maintenance of biodiversity in highly
      diverse communities. The concept of niche and associated theories predict that
      competition for available ecological space leads to a ceiling in species richness
      that influences further diversification patterns. By contrast, the neutral theory
      supports that speciation is stochastic and diversity independent. We examined the
      phylogenetic community structure and diversification rates in three families and
      14 sites within coral reef fish communities from the Indian and Pacific oceans.
      Using the phylogenetic relationships among 157 species estimated with 2300 bp of
      mitochondrial DNA, we tested predictions in terms of species coexistence from the
      neutral and niche theories. At the regional scale, our findings suggest that
      phylogenetic community structure shifts during community assembly to a pattern of
      dispersion as a consequence of allopatric speciation in recent times but overall,
      variations in diversification rates did not relate with sea level changes. At the
      local scale, the phylogenetic community structure is consistent with a neutral
      model of community assembly since no departure from a random sorting of species
      was observed. The present results support a neutral model of community assembly
      as a consequence of the stochastic and unpredictable nature of coral reefs
      favoring generalist and sedentary species competing for living space rather than
      trophic resources. As a consequence, the observed decrease in diversification
      rates may be seen as the result of a limited supply of living space as expected
      in a finite island model.

PMID- 22393500
TI  - Know when to run, know when to hide: can behavioral differences explain the
      divergent invasion success of two sympatric lizards?
AB  - Invasive species represent a select subset of organisms that have successfully
      transitioned through each stage of the introduction process (transportation,
      establishment, and spread). Although there is a growing realization that behavior
      plays a critical role in invasion success, few studies have focused on the
      initial stages of introduction. We examined whether differences in the grouping
      tendencies and exploratory behavior of two sympatric lizard species could
      contribute to their divergent invasion success. While the nondirected activity of
      the two species did not differ, the invasive delicate skink (Lampropholis
      delicata) was found to be more exploratory than the congeneric noninvasive garden
      skink (L. guichenoti), which enabled it to more effectively locate novel
      environments and basking site resources. The delicate skink also exhibited a
      greater tendency to hide, which may act to enhance its probability of ensnarement
      in freight and cargo and decrease its likelihood of detection during transit. The
      grouping tendencies of the two species did not differ. Together, our results
      suggest that while the two species have an equivalent "opportunity" for
      unintentional human-assisted transportation, several pre-existing behavioral
      traits may enhance the success of the delicate skink in negotiating the initial
      stages of the introduction process, and subsequent post-establishment spread.

PMID- 22393501
TI  - Is the degree of clonality of forest herbs dependent on gap age? Using
      fingerprinting approaches to assess optimum successional stages for montane
      forest herbs.
AB  - Using molecular fingerprinting (amplified fragment length polymorphism [AFLP]
      method), we explored the potential of small-scale population analysis for
      understanding colonization patterns of herb layer species in forests after canopy
      disturbance. We investigated three common forest understorey species with
      different life forms (Trientalis europaea, Calamagrostis villosa, and Vaccinium
      myrtillus) in the Harz Mountains in Germany in three different gap age classes
      and undisturbed forest. For two of them (T. europaea and C. villosa), we analyzed
      clone sizes and clonal structure. We hypothesized that clone sizes depend on age
      since gap formation and are affected by light availability. Mean patch sizes of
      V. myrtillus, T. europaea, and C. villosa formed were 3.7 m(2), 27.9 m(2), and
      40.6 m(2), respectively. Trientalis europaea and C. villosa patches consisted
      mostly of more than one genet. Largest clone sizes of T. europaea were
      encountered in gaps of intermediate successional age (15-60 years, averaged
      minimum estimation of clone sizes: 6.56 m(2)) whereas clone size of C. villosa
      was found to be independent from gap age and had a mean minimum clone size of
      0.49 m(2). In both species, clone size was positively related to light
      availability. Additionally, there was a positive relationship between clone size
      and ramet density for T. europaea and C. villosa. Genetic variation was higher
      within populations of T. europaea and C. villosa than among populations.
      Trientalis europaea was the only species with a clear genetic isolation by
      distance, pointing at an equilibrium between gene flow and genetic drift. In
      conclusion, we showed that forest canopy gap dynamics clearly affect the small
      scale structure of populations of understorey plants. Species with high lateral
      growth rates, such as T. europaea offer the possibility to serve as "ecological
      clock" for dating ecological processes.

PMID- 22393502
TI  - Do mycorrhizal network benefits to survival and growth of interior Douglas-fir
      seedlings increase with soil moisture stress?
AB  - Facilitation of tree establishment by ectomycorrhizal (EM) networks (MNs) may
      become increasingly important as drought stress increases with climate change in
      some forested regions of North America. The objective of this study was to
      determine (1) whether temperature, CO(2) concentration ([CO(2)]), soil moisture,
      and MNs interact to affect plant establishment success, such that MNs facilitate
      establishment when plants are the most water stressed, and (2) whether transfer
      of C and water between plants through MNs plays a role in this. We established
      interior Douglas-fir (Pseudotsuga menziesiivar.glauca) seedlings in root boxes
      with and without the potential to form MNs with nearby conspecific seedlings that
      had consistent access to water via their taproots. We varied temperature,
      [CO(2)], and soil moisture in growth chambers. Douglas-fir seedling survival
      increased when the potential existed to form an MN. Growth increased with MN
      potential under the driest soil conditions, but decreased with temperature at 800
      ppm [CO(2)]. Transfer of (13)C to receiver seedlings was unaffected by potential
      to form an MN with donor seedlings, but deuterated water (D(2)O) transfer
      increased with MN potential under ambient [CO(2)]. Chlorophyll fluorescence was
      reduced when seedlings had the potential to form an MN under high [CO(2)] and
      cool temperatures. We conclude that Douglas-fir seedling establishment in
      laboratory conditions is facilitated by MN potential where Douglas-fir seedlings
      have consistent access to water. Moreover, this facilitation appears to increase
      as water stress potential increases and water transfer via networks may play a
      role in this. These results suggest that conservation of MN potential may be
      important to forest regeneration where drought stress increases with climate
      change.

PMID- 22393503
TI  - Conspecific brood parasitism in the tropics: an experimental investigation of
      host responses in common moorhens and American purple gallinules.
AB  - Species occupying a broad latitudinal range may show greater phenotypic
      plasticity in behavior than species with smaller ranges or more specific habitat
      requirements. This study investigates for the first time the occurrence of
      conspecific brood parasitism (CBP) in sympatric tropical populations of the
      common moorhen (Gallinula chloropus pauxilla Bangs) and the American purple
      gallinule (Porphyrula martinica L.). CBP occurred in at least 20% (N = 76) of
      common moorhen nests on the Rio Chagres in Panama. Half (N = 20) of the parasitic
      eggs were accepted, but 10 were destroyed or ejected from host nests.
      Introductions of experimental eggs into nests revealed hosts were more likely to
      accept parasitism later in the host's laying period and during incubation,
      consistent with expectation of an adaptive response. CBP was not detected in a
      small sympatric population of American purple gallinules. Members of this
      population did not eject experimental eggs, suggesting a lack of experience with
      costly CBP. Contrasting ecological factors help explain why these two species of
      rail (Family Rallidae) differ in regard to CBP. Purple gallinule territories were
      sparse, owing to the distribution of preferred habitat. Moorhens flocked outside
      of the breeding season. They nested more synchronously, at higher densities, and
      primarily in ephemeral floating vegetation. Further, moorhens suffered a rate of
      nest loss nearly double that of American purple gallinules, and this increased
      over the course of the breeding season. Moorhen clutches were larger on average,
      and more variable in size than those of purple gallinules. Reproductive effort
      and rate (seasonality) constitute important life history differences between
      these species that may constrain the evolution of reproductive tactics. Comparing
      these sympatric populations, and others differing in life-history traits and
      ecological constraints, highlights the role of risk management in the evolution
      of CBP.

PMID- 22393504
TI  - Phylogeography of the Mekong mud snake (Enhydris subtaeniata): the biogeographic
      importance of dynamic river drainages and fluctuating sea levels for semiaquatic
      taxa in Indochina.
AB  - During the Cenozoic, Southeast Asia was profoundly affected by plate tectonic
      events, dynamic river systems, fluctuating sea levels, shifting coastlines, and
      climatic variation, which have influenced the ecological and evolutionary
      trajectories of the Southeast Asian flora and fauna. We examined the role of
      these paleogeographic factors on shaping phylogeographic patterns focusing on a
      species of semiaquatic snake, Enhydris subtaeniata (Serpentes: Homalopsidae)
      using sequence data from three mitochondrial fragments (cytochrome b, ND4, and
      ATPase-2785 bp). We sampled E. subtaeniata from seven locations in three river
      drainage basins that encompassed most of this species' range. Genetic diversities
      were typically low within locations but high across locations. Moreover, each
      location had a unique suite of haplotypes not shared among locations, and
      pairwise phi(ST) values (0.713-0.998) were highly significant between all
      location pairs. Relationships among phylogroups were well resolved and analysis
      of molecular variance (AMOVA) revealed strong geographical partitioning of
      genetic variance among the three river drainage basins surveyed. The genetic
      differences observed among the populations of E. subtaeniata were likely shaped
      by the Quaternary landscapes of Indochina and the Sunda Shelf. Historically, the
      middle and lower Mekong consisted of strongly dissected river valleys separated
      by low mountain ranges and much of the Sunda Shelf consisted of lowland river
      valleys that served to connect faunas associated with major regional rivers. It
      is thus likely that the contemporary genetic patterns observed among populations
      of E. subtaeniata are the result of their histories in a complex terrain that
      created abundant opportunities for genetic isolation and divergence yet also
      provided lowland connections across now drowned river valleys.

PMID- 22393505
TI  - Postglacial recolonization of eastern Blacknose Dace,Rhinichthys
      atratulus(Teleostei: Cyprinidae), through the gateway of New England.
AB  - During the last ice age, much of North America far south as 40 degrees N was
      covered by glaciers (Hewitt 2000). About 20,000 years ago, as the glaciers
      retreated, the hydrologic landscape changed dramatically creating waterways for
      fish dispersal. The number of populations responsible for recolonization and the
      regions from which they recolonized are unknown for many freshwater fishes living
      in New England and southeastern Canada. The Blacknose Dace,Rhinichthys atratulus,
      is one of the freshwater fish species that recolonized this region. We
      hypothesize that the earliest deglaciated region, modern-day Connecticut, was
      recolonized byR. atratulusvia a single founding event by a single population. In
      this paper, we test this hypothesis phylogenetically with regard to the major
      drainage basins within Connecticut. The mitochondrial DNA exhibits low nucleotide
      diversity, high haplotype diversity, and a dominant haplotype found across the
      state. A small percentage of individuals in the Housatonic drainage basin,
      however, share a haplotype with populations in New York drainage basins, a
      haplotype not found elsewhere in Connecticut's drainage basins. We calculated a
      range for the rate of divergence for NADH dehydrogenase subunit 2 (nd2) and
      control region (ctr) of 4.43-6.76% and 3.84-8.48% per million years (my),
      respectively. While this range is higher than the commonly accepted rate of 2%
      for mitochondrial DNA, these results join a growing list of publications finding
      high rates of divergence for various taxa (Peterson and Masel 2009). The data
      support the conclusion that Connecticut as a whole was recolonized initially by a
      single founding event that came from a single refugium. Subsequently, the
      Housatonic basin alone experienced a secondary recolonization event.

PMID- 22393506
TI  - Complex pattern of genetic structuring in the Atlantic salmon (Salmo salar L.) of
      the River Foyle system in northwest Ireland: disentangling the evolutionary
      signal from population stochasticity.
AB  - Little is known about the microevolutionary processes shaping within river
      population genetic structure of aquatic organisms characterized by high levels of
      homing and spawning site fidelity. Using a microsatellite panel, we observed
      complex and highly significant levels of intrariver population genetic
      substructure and Isolation-by-Distance, in the Atlantic salmon stock of a large
      river system. Two evolutionary models have been considered explaining mechanisms
      promoting genetic substructuring in Atlantic salmon, the member-vagrant and
      metapopulation models. We show that both models can be simultaneously used to
      explain patterns and levels of population structuring within the Foyle system. We
      show that anthropogenic factors have had a large influence on contemporary
      population structure observed. In an analytical development, we found that the
      frequently used estimator of genetic differentiation, F(ST), routinely
      underestimated genetic differentiation by a factor three to four compared to the
      equivalent statistic Jost's D(est) (Jost 2008). These statistics also showed a
      near-perfect correlation. Despite ongoing discussions regarding the usefulness of
      "adjusted"F(ST) statistics, we argue that these could be useful to identify and
      quantify qualitative differences between populations, which are important from
      management and conservation perspectives as an indicator of existence of
      biologically significant variation among tributary populations or a warning of
      critical environmental damage.

PMID- 22393507
TI  - Comprehensive study of mtDNA among Southwest Asian dogs contradicts independent
      domestication of wolf, but implies dog-wolf hybridization.
AB  - Studies of mitochondrial DNA (mtDNA) diversity indicate explicitly that dogs were
      domesticated, probably exclusively, in southern East Asia. However, Southwest
      Asia (SwAsia) has had poor representation and geographical coverage in these
      studies. Other studies based on archaeological and genome-wide SNP data have
      suggested an origin of dogs in SwAsia. Hence, it has been suspected that mtDNA
      evidence for this scenario may have remained undetected. In the first
      comprehensive investigation of genetic diversity among SwAsian dogs, we analyzed
      582 bp of mtDNA for 345 indigenous dogs from across SwAsia, and compared with
      1556 dogs across the Old World. We show that 97.4% of SwAsian dogs carry
      haplotypes belonging to a universal mtDNA gene pool, but that only a subset of
      this pool, five of the 10 principal haplogroups, is represented in SwAsia. A high
      frequency of haplogroup B, potentially signifying a local origin, was not
      paralleled with the high genetic diversity expected for a center of origin.
      Meanwhile, 2.6% of the SwAsian dogs carried the rare non-universal haplogroup d2.
      Thus, mtDNA data give no indication that dogs originated in SwAsia through
      independent domestication of wolf, but dog-wolf hybridization may have formed the
      local haplogroup d2 within this region. Southern East Asia remains the only
      region with virtually full extent of genetic variation, strongly indicating it to
      be the primary and probably sole center of wolf domestication. An origin of dogs
      in southern East Asia may have been overlooked by other studies due to a
      substantial lack of samples from this region.

PMID- 22393508
TI  - Trait-mediated diversification in nematode predator-prey systems.
AB  - Nematodes are presumably the most numerous Metazoans in terrestrial habitats.
      They are represented at all trophic levels and are known to respond to nutrient
      limitation, prey availability, and microbial resources. Predatory nematodes
      reside at the highest trophic level, and as such their feeding habits could have
      a major impact on soil food web functioning. Here, we investigate the effects of
      gender and developmental stage on the nematode body sizes in coarse and loamy
      soils. Besides Neodiplogasteridae, our predators are much larger than other soil
      dwelling nematodes from their early developmental stage onwards. From juvenile to
      adult, the predatory Aporcelaimellus (Kruskal-Wallis P < 0.001), Dorylaimoides,
      and Tripyla (both P < 0.01) show great length increases during their
      developmental growth, in contrast to their possible prey (almost all P < 0.001).
      Less than 4% of the prey exceeds the length of the predatory adults, but more
      than 30% of the prey exceeds the length of the predatory juveniles. Potential
      body size ratios and some physical problems experienced by small fluid feeders
      attacking large prey are discussed in an attempt to summarize different prey
      searching mechanisms and aggregative predatory responses in the soil system.

PMID- 22393509
TI  - Genetic and phenotypic differentiation between invasive and native Rhododendron
      (Ericaceae) taxa and the role of hybridization.
AB  - Hybridization has been repeatedly put forward to explain the invasiveness of
      Rhododendron ponticum L. in the British Isles. The present study investigates the
      pattern of ecotypic differentiation and hybridization among native North American
      R. catawbiense and R. maximum, native R. ponticum from Georgia and Spain, and
      invasive R. ponticum from Ireland and aims to assess the contribution of
      hybridization for Rhododendron invasion in the British Isles. Six populations per
      taxon were analyzed with AFLP markers for genetic dissimilarity, subjected to
      germination and growth experiments, and tested for frost hardiness. We assessed
      variation in morphological and ecological characteristics to identify traits
      displaying evidence of hybridization, thus, promoting invasiveness. Molecular
      marker analyses revealed a clear distinction between North American R.
      catawbiense and R. maximum on the one hand, and all R. ponticum populations on
      the other hand, displaying a complete intermixture of native Spanish and invasive
      Irish populations. Multivariate analyses of traits revealed leaf length-width
      ratio, relative growth rates (RGRs) in leaf length, root biomass, and shoot-root
      ratio to significantly discriminate between the different taxa and unequivocally
      assigned invasive Irish R. ponticum to the Spanish phenotypes. While the Irish R.
      ponticum had similar growth traits as conspecific native R. ponticum provenances,
      germination and biomass allocation were more similar to North American R.
      catawbiense and R. maximum. Hybridization did not contribute to explaining
      invasiveness of R. ponticum in Ireland. The similarity in germination and biomass
      allocation of invasive Irish R. ponticum and North American species has evolved
      independently and can more probably be attributed to an independent shift within
      the Ponticum cluster in Ireland.

PMID- 22393510
TI  - Conservation priorities of genetic diversity in domesticated metapopulations: a
      study in taurine cattle breeds.
AB  - We estimated neutral diversity of 21 European cattle breeds with 105
      microsatellites. Nine of them resembled unselected Balkan Busa strains with
      diffuse breeding barriers and the 12 others were strongly differentiated,
      isolated breeds. Because of the impact of neutral genetic diversity on long-term
      population adaptive capacity, we discuss the long-term outcome of different
      conservation priorities in a subdivided metapopulation of the investigated cattle
      breeds. The optimal contribution to a pool of total genetic diversity allocated
      more than 95% of long-term relevant neutral diversity to virtually unselected
      strains of the Balkan Busa, while the maximization of total variance preferred
      inbred breeds. Current artificial selection methods, such as genomic selection
      sped up and a recovery of underestimated traits becomes quickly impossible. We
      emphasize that currently neutral and even deleterious alleles might be required
      for future genotypes in sustainable and efficient livestock breeding and
      production systems of a 21st century. We provide cumulative evidences that long
      term survival relies on genetic complexity and complexity relies on allelic
      diversity. Our results suggest that virtually unselected, nonuniform strains
      harbor a crucial proportion of neutral diversity and should be conserved with
      high global priority. As one example, we suggest a cooperative maintenance of the
      nondifferentiated, highly fragmented, and fast vanishing metapopulation of Balkan
      Busa.

PMID- 22393511
TI  - Stocks of carbon and nitrogen and partitioning between above- and belowground
      pools in the Brazilian coastal Atlantic Forest elevation range.
AB  - We estimated carbon and nitrogen stocks in aboveground biomass (AGB) and
      belowground biomass (BGB) along an elevation range in forest sites located on the
      steep slopes of the Serra do Mar on the north coast of the State of Sao Paulo,
      southeast Brazil. In elevations of 100 m (lowland), 400 m (submontane), and 1000
      m (montane) four 1-ha plots were established, and above- (live and dead) and
      belowground (live and dead) biomass were determined. Carbon and nitrogen
      concentrations in each compartment were determined and used to convert biomass
      into carbon and nitrogen stocks. The carbon aboveground stock (C(AGB)) varied
      along the elevation range from approximately 110 to 150 Mg.ha(-1), and nitrogen
      aboveground stock (N(AGB)), varied from approximately 1.0 to 1.9 Mg.ha(-1). The
      carbon belowground stock (C(BGB)) and the nitrogen belowground stock (N(BGB))
      were significantly higher than the AGB and varied along the elevation range from
      approximately 200-300 Mg.ha(-1), and from 14 to 20 Mg.ha(-1), respectively.
      Finally, the total carbon stock (C(TOTAL)) varied from approximately 320 to 460
      Mg.ha(-1), and the nitrogen total stock (N(TOTAL)) from approximately 15 to 22
      Mg.ha(-1). Most of the carbon and nitrogen stocks were found belowground and not
      aboveground as normally found in lowland tropical forests. The above- and
      belowground stocks, and consequently, the total stocks of carbon and nitrogen
      increased significantly with elevation. As the soil and air temperature also
      decreased significantly with elevation, we found a significantly inverse
      relationship between carbon and nitrogen stocks and temperature. Using this
      inverse relationship, we made a first approach estimate that an increase of 1
      degrees C in soil temperature would decrease the carbon and nitrogen stocks in
      approximately 17 Mg.ha(-1) and 1 Mg.ha(-1) of carbon and nitrogen, respectively.

PMID- 22393512
TI  - Nocturnal water loss in mature subalpine Eucalyptus delegatensis tall open
      forests and adjacent E. pauciflora woodlands.
AB  - We measured sap flux (S) and environmental variables in four monospecific stands
      of alpine ash (Eucalyptus delegatensis R. Baker, AA) and snowgum (E. pauciflora
      Sieb. ex Spreng., SG) in Australia's Victorian Alps. Nocturnal S was 11.8 +/-
      0.8% of diel totals. We separated transpiration (E) and refilling components of S
      using a novel modeling approach based on refilling time constants. The nocturnal
      fraction of diel water loss (f(n)) averaged 8.6 +/- 0.6% for AA and 9.8 +/- 1.7%
      for SG; f(n) differed among sites but not species. Evaporative demand (D) was the
      strongest driver of nocturnal E (E(n)). The ratio E(n)/D (G(n)) was positively
      correlated to soil moisture in most cases, whereas correlations between wind
      speed and G(n) varied widely in sign and strength. Our results suggest (1) the
      large, mature trees at our subalpine sites have greater f(n) than the few
      Australian native tree species that have been studied at lower elevations, (2) AA
      and SG exhibit similar f(n) despite very different size and life history, and (3)
      f(n) may differ substantially among sites, so future work should be replicated
      across differing sites. Our novel approach to quantifying f(n) can be applied to
      S measurements obtained by any method.

PMID- 22393513
TI  - Three QTL in the honey bee Apis mellifera L. suppress reproduction of the
      parasitic mite Varroa destructor.
AB  - Varroa destructor is a highly virulent ectoparasitic mite of the honey bee Apis
      mellifera and a major cause of colony losses for global apiculture. Typically,
      chemical treatment is essential to control the parasite population in the honey
      bee colony. Nevertheless a few honey bee populations survive mite infestation
      without any treatment. We used one such Varroa mite tolerant honey bee lineage
      from the island of Gotland, Sweden, to identify quantitative trait loci (QTL)
      controlling reduced mite reproduction. We crossed a queen from this tolerant
      population with drones from susceptible colonies to rear hybrid queens. Two
      hybrid queens were used to produce a mapping population of haploid drones. We
      discriminated drone pupae with and without mite reproduction, and screened the
      genome for potential QTL using a total of 216 heterozygous microsatellite markers
      in a bulk segregant analysis. Subsequently, we fine mapped three candidate target
      regions on chromosomes 4, 7, and 9. Although the individual effect of these three
      QTL was found to be relatively small, the set of all three had significant impact
      on suppression of V. destructor reproduction by epistasis. Although it is in
      principle possible to use these loci for marker-assisted selection, the strong
      epistatic effects between the three loci complicate selective breeding programs
      with the Gotland Varroa tolerant honey bee stock.

PMID- 22393514
TI  - Differential timing of gene expression regulation between leptocephali of the two
      Anguilla eel species in the Sargasso Sea.
AB  - The unique life-history characteristics of North Atlantic catadromous eels have
      long intrigued evolutionary biologists, especially with respect to mechanisms
      that could explain their persistence as two ecologically very similar but
      reproductively and geographically distinct species. Differential developmental
      schedules during young larval stages have commonly been hypothesized to represent
      such a key mechanism. We performed a comparative analysis of gene expression by
      means of microarray experiments with American and European eel leptocephali
      collected in the Sargasso Sea in order to test the alternative hypotheses of (1)
      differential timing of gene expression regulation during early development versus
      (2) species-specific differences in expression of particular genes. Our results
      provide much stronger support for the former hypothesis since no gene showed
      consistent significant differences in expression levels between the two species.
      In contrast, 146 genes showed differential timings of expression between species,
      although the observed expression level differences between the species were
      generally small. Consequently, species-specific gene expression regulation seems
      to play a minor role in species differentiation. Overall, these results show that
      the basis of the early developmental divergence between the American and European
      eel is probably influenced by differences in the timing of gene expression
      regulation for genes involved in a large array of biological functions.

PMID- 22393515
TI  - Pristionchus uniformis, should I stay or should I go? Recent host range expansion
      in a European nematode.
AB  - Pristionchus pacificus has been developed as a model system in evolutionary
      developmental biology, evolutionary ecology, and population genetics. This
      species has a well-known ecological association with scarab beetles. Generally,
      Pristionchus nematodes have a necromenic association with their beetle hosts.
      Arrested dauer larvae invade the insect and wait for the host's death to resume
      development. Only one Pristionchus species is known to frequently associate with
      a non-scarab beetle. Pristionchus uniformis has been isolated from the
      chrysomelid Leptinotarsa decemlineata, also known as the Colorado potato beetle,
      in Europe and North America, but is also found on scarab beetles. This unusual
      pattern of association with two unrelated groups of beetles on two continents
      requires the involvement of geographical and host range expansion events. Here,
      we characterized a collection of 81 P. uniformis isolates from North America and
      Europe and from both scarab beetles and L. decemlineata. We used population
      genetic and phylogenetic analyses of the mitochondrial gene nd2 to reconstruct
      the genetic history of P. uniformis and its beetle association. Olfactory tests
      on beetles chemical extracts showed that P. uniformis has a unique
      chemoattractive profile toward its beetle hosts. Our results provide evidence for
      host range expansion through host-switching events in Europe where P. uniformis
      was originally associated with scarab beetles and the nematode's subsequent
      invasion of North America.

PMID- 22393516
TI  - Population-specific demography and invasion potential in medfly.
AB  - Biological invasions are constantly gaining recognition as a significant
      component of global change. The Mediterranean fruit fly (medfly) constitutes an
      ideal model species for the study of biological invasions due to its (1) almost
      cosmopolitan geographic distribution, (2) huge economic importance, and (3) well
      documented invasion history. Under a common garden experimental set up, we tested
      the hypothesis that medfly populations obtained from six global regions [Africa
      (Kenya), Pacific (Hawaii), Central America (Guatemala), South America (Brazil),
      Extra-Mediterranean (Portugal), and Mediterranean (Greece)] have diverged in
      important immature life-history traits such as preadult survival and
      developmental times. We also tested the hypothesis that medfly populations from
      the above regions exhibit different population growth rates. For this purpose,
      data on the life history of immatures were combined with adult survival and
      reproduction data derived from an earlier study in order to calculate population
      parameters for the above six populations. Our results clearly show that medfly
      populations worldwide exhibit significant differences in preadult survival,
      developmental rates of immatures and important population parameters such as the
      intrinsic rate of increase. Therefore, geographically isolated medfly populations
      may share different invasion potential, since population growth rates could
      influence basic population processes that operate mostly during the last two
      stages of an invasion event, such as establishment and spread. Our findings
      provide valuable information for designing population suppression measures and
      managing invasiveness of medfly populations worldwide.

PMID- 22393517
TI  - Parallel changes in the taxonomical structure of bacterial communities exposed to
      a similar environmental disturbance.
AB  - Bacterial communities play a central role in ecosystems, by regulating
      biogeochemical fluxes. Therefore, understanding how multiple functional
      interactions between species face environmental perturbations is a major concern
      in conservation biology. Because bacteria can use several strategies, including
      horizontal gene transfers (HGT), to cope with rapidly changing environmental
      conditions, potential decoupling between function and taxonomy makes the use of a
      given species as a general bioindicator problematic. The present work is a first
      step to characterize the impact of a recent polymetallic gradient over the
      taxonomical networks of five lacustrine bacterial communities. Given that
      evolutionary convergence represents one of the best illustration of natural
      selection, we focused on a system composed of two pairs of impacted and clean
      lakes in order to test whether similar perturbation exerts a comparable impact on
      the taxonomical networks of independent bacterial communities. First, we showed
      that similar environmental stress drove parallel structural changes at the
      taxonomic level on two independent bacterial communities. Second, we showed that
      a long-term exposure to contaminant gradients drove significant taxonomic
      structure changes within three interconnected bacterial communities. Thus, this
      model lake system is relevant to characterize the strategies, namely acclimation
      and/or adaptation, of bacterial communities facing environmental perturbations,
      such as metal contamination.

PMID- 22393518
TI  - Strong spatial genetic structure in five tropical Piper species: should the Baker
      Fedorov hypothesis be revived for tropical shrubs?
AB  - Fifty years ago, Baker and Fedorov proposed that the high species diversity of
      tropical forests could arise from the combined effects of inbreeding and genetic
      drift leading to population differentiation and eventually to sympatric
      speciation. Decades of research, however have failed to support the Baker-Fedorov
      hypothesis (BFH), and it has now been discarded in favor of a paradigm where most
      trees are self-incompatible or strongly outcrossing, and where long-distance
      pollen dispersal prevents population drift. Here, we propose that several hyper
      diverse genera of tropical herbs and shrubs, including Piper (>1,000 species),
      may provide an exception. Species in this genus often have aggregated, high
      density populations with self-compatible breeding systems; characteristics which
      the BFH would predict lead to high local genetic differentiation. We test this
      prediction for five Piper species on Barro Colorado Island, Panama, using
      Amplified Fragment Length Polymorphism (AFLP) markers. All species showed strong
      genetic structure at both fine- and large-spatial scales. Over short distances
      (200-750 m) populations showed significant genetic differentiation (Fst 0.11
      0.46, P < 0.05), with values of spatial genetic structure that exceed those
      reported for other tropical tree species (Sp = 0.03-0.136). This genetic
      structure probably results from the combined effects of limited seed and pollen
      dispersal, clonal spread, and selfing. These processes are likely to have
      facilitated the diversification of populations in response to local natural
      selection or genetic drift and may explain the remarkable diversity of this rich
      genus.

PMID- 22393519
TI  - Body mass explains characteristic scales of habitat selection in terrestrial
      mammals.
AB  - Niche theory in its various forms is based on those environmental factors that
      permit species persistence, but less work has focused on defining the extent, or
      size, of a species' environment: the area that explains a species' presence at a
      point in space. We proposed that this habitat extent is identifiable from a
      characteristic scale of habitat selection, the spatial scale at which habitat
      best explains species' occurrence. We hypothesized that this scale is predicted
      by body size. We tested this hypothesis on 12 sympatric terrestrial mammal
      species in the Canadian Rocky Mountains. For each species, habitat models varied
      across the 20 spatial scales tested. For six species, we found a characteristic
      scale; this scale was explained by species' body mass in a quadratic
      relationship. Habitat measured at large scales best-predicted habitat selection
      in both large and small species, and small scales predict habitat extent in
      medium-sized species. The relationship between body size and habitat selection
      scale implies evolutionary adaptation to landscape heterogeneity as the driver of
      scale-dependent habitat selection.

PMID- 22393520
TI  - Range-wide genetic population structure of common pochard (Aythya ferina): a
      potentially important vector of highly pathogenic avian influenza viruses.
AB  - An understanding of the distribution and spatial structure of the natural vectors
      of zoonothic pathogens is of interest for effective disease control and
      prevention. Here, we investigate the range-wide population genetic structure of
      common pochard (Aythya ferina), a long-distance migratory duck and potential
      vector of highly pathogenic avian influenza. We collected several hundred samples
      from breeding and wintering grounds across Eurasia including some H5N1-positive
      individuals and generated partial sequences of the mitochondrial control region
      and multilocus microsatellite genotypes. Genetic differentiation among breeding
      populations was significant for both marker types but higher for maternally
      inherited mtDNA than for biparentally inherited nuclear markers. There was only
      weak genetic divergence between ducks sampled in Europe and East Asia, and
      genetic differentiation between populations was not generally associated with
      geographical distance. No evidence of genetic substructure was detected for ducks
      sampled on the European wintering grounds. Our results suggest limited breeding
      site fidelity, especially in females, but extensive population admixture on the
      wintering grounds. The specific role of pochards as natural vectors of zoonotic
      pathogens and in particular H5N1 remains to be clarified but our results point to
      wintering grounds as potential hotspots for disease transmission.

PMID- 22393521
TI  - Experimental manipulation shows that the white wing patch in collared flycatchers
      is a male sexual ornament.
AB  - Descriptive analysis suggests that a conspicuous white wing patch in dichromatic
      (black and white) pied and collared flycatchers is under sexual selection. Here,
      we use an experimental approach to test whether this trait is indeed the target
      of selection. We caught 100 collared flycatcher Ficedula albicollis males soon
      after their arrival on the breeding site. We reduced (blackened) part of the
      white wing patch in half of these males and recorded their mating success and
      within and extra-pair offspring production. Reduction of the size of the white
      wing patch lowered a male's probability to attract a secondary social female, but
      not a primary female. However, primary females paired to males with a reduced
      wing patch were smaller (in tarsus), suggesting that male choice of partner or
      female-female competition over mates occurs in this species. The probability of
      pairing with a primary female (but not other components of male reproductive
      success) declined with arrival time (proxied by the date of capture). Males with
      a reduced wing patch size tended to sire less extra-pair offspring, although this
      relationship was reversed in one of the three study plots, suggesting that mating
      dynamics are context dependent. While our findings show that wing patch size is
      the target of sexual selection, the pathways and the strength of selection on
      this ornament differed markedly from a previous descriptive study.
      Nonexperimental studies of sexual selection in the wild may overestimate its
      importance because male fitness and ornamentation both depend positively on
      environmental conditions.

PMID- 22393522
TI  - High-throughput sequencing offers insight into mechanisms of resource
      partitioning in cryptic bat species.
AB  - Sympatric cryptic species, characterized by low morphological differentiation,
      pose a challenge to understanding the role of interspecific competition in
      structuring ecological communities. We used traditional (morphological) and novel
      molecular methods of diet analysis to study the diet of two cryptic bat species
      that are sympatric in southern England (Plecotus austriacus and P. auritus) (Fig.
      1). Using Roche FLX 454 (Roche, Basel, CH) high-throughput sequencing (HTS) and
      uniquely tagged generic arthropod primers, we identified 142 prey Molecular
      Operational Taxonomic Units (MOTUs) in the diet of the cryptic bats, 60% of which
      were assigned to a likely species or genus. The findings from the molecular study
      supported the results of microscopic analyses in showing that the diets of both
      species were dominated by lepidopterans. However, HTS provided a sufficiently
      high resolution of prey identification to determine fine-scale differences in
      resource use. Although both bat species appeared to have a generalist diet, eared
      moths from the family Noctuidae were the main prey consumed. Interspecific niche
      overlap was greater than expected by chance (O(jk) = 0.72, P < 0.001) due to
      overlap in the consumption of the more common prey species. Yet, habitat
      associations of nongeneralist prey species found in the diets corresponded to
      those of their respective bat predator (grasslands for P. austriacus, and
      woodland for P. auritus). Overlap in common dietary resource use combined with
      differential specialist prey habitat associations suggests that habitat
      partitioning is the primary mechanism of coexistence. The performance of HTS is
      discussed in relation to previous methods of molecular and morphological diet
      analysis. By enabling species-level identification of dietary components, the
      application of DNA sequencing to diet analysis allows a more comprehensive
      comparison of the diet of sympatric cryptic species, and therefore can be an
      important tool for determining fine-scale mechanisms of coexistence.

PMID- 22393523
TI  - Ecological release in White Sands lizards.
AB  - Ecological opportunity is any change that allows populations to escape selection
      from competition and predation. After encountering ecological opportunity,
      populations may experience ecological release: enlarged population size,
      broadened resource use, and/or increased morphological variation. We identified
      ecological opportunity and tested for ecological release in three lizard
      colonists of White Sands, New Mexico (Sceloporus undulatus, Holbrookia maculata,
      and Aspidoscelis inornata). First, we provide evidence for ecological opportunity
      by demonstrating reduced species richness and abundance of potential competitors
      and predators at White Sands relative to nearby dark soils habitats. Second, we
      characterize ecological release at White Sands by demonstrating density
      compensation in the three White Sands lizard species and expanded resource use in
      White Sands S. undulatus. Contrary to predictions from ecological release models,
      we observed directional trait change but not increased trait variation in S.
      undulatus. Our results suggest that ecological opportunity and ecological release
      can be identified in natural populations, especially those that have recently
      colonized isolated ecosystems.

PMID- 22393524
TI  - Harbour porpoises respond to climate change.
AB  - The effects of climate change on marine ecosystems and in particular on marine
      top predators are difficult to assess due to, among other things, spatial
      variability, and lack of clear delineation of marine habitats. The banks of West
      Greenland are located in a climate sensitive area and are likely to elicit
      pronounced responses to oceanographic changes in the North Atlantic. The recent
      increase in sea temperatures on the banks of West Greenland has had cascading
      effects on sea ice coverage, residency of top predators, and abundance of
      important prey species like Atlantic cod (Gadus morhua). Here, we report on the
      response of one of the top predators in West Greenland; the harbour porpoise
      (Phocoena phocoena). The porpoises depend on locating high densities of prey
      species with high nutritive value and they have apparently responded to the
      general warming on the banks of West Greenland by longer residence times,
      increased consumption of Atlantic cod resulting in improved body condition in the
      form of larger fat deposits in blubber, compared to the situation during a cold
      period in the 1990s. This is one of the few examples of a measurable effect of
      climate change on a marine mammal population.

PMID- 22393525
TI  - Terrestrial chemical cues help coral reef fish larvae locate settlement habitat
      surrounding islands.
AB  - Understanding the degree of connectivity between coastal and island landscapes
      and nearby coral reefs is vital to the integrated management of terrestrial and
      marine environments in the tropics. Coral reef fish are capable of navigating
      appropriate settlement habitats following their pelagic larval phase, but the
      mechanisms by which they do this are unclear. The importance of olfactory cues in
      settlement site selection has been demonstrated, and there is increasing evidence
      that chemical cues from terrestrial sources may be important for some species.
      Here, we test the olfactory preferences of eight island-associated coral reef
      fish recruits and one generalist species to discern the capacity for terrestrial
      cue recognition that may aid in settlement site selection. A series of pairwise
      choice experiments were used to evaluate the potential role that terrestrial,
      water-borne olfactory cues play in island-reef recognition. Olfactory stimuli
      tested included near-shore water, terrestrial rainforest leaf litter, and
      olfactory cues collected from different reef types (reefs surrounding vegetated
      islands, and reefs with no islands present). All eight island-associated species
      demonstrated high levels of olfactory discrimination and responded positively
      toward olfactory cues indicating the presence of a vegetated island. We
      hypothesize that although these fish use a suite of cues for settlement site
      recognition, one mechanism in locating their island/reef habitat is through the
      olfactory cues produced by vegetated islands. This research highlights the role
      terrestrial olfactory cues play in large-scale settlement site selection and
      suggests a high degree of ecosystem connectivity.

PMID- 22393526
TI  - "Cost" of virginity in wild Drosophila melanogaster females.
AB  - Laboratory studies have revealed a significant "cost of mating" to Drosophila
      melanogaster females in the form of reduced longevity. The effect is attributable
      to nonsperm components of the ejaculate. Female D. melanogaster are known to mate
      up to six times in nature, and given that they do not typically remate daily, it
      raises the question as to the extent to which the longevity of wild mated females
      is reduced. Here I addressed this question by comparing the longevity of wild
      virgin females, collected as they emerged from rotting fruit, to the longevity of
      randomly collected mature females at the same site. Because the randomly
      collected females all were inseminated and were fully pigmented at the time of
      collection, they already were older than the virgins when the experiment began.
      Contrary to expectations from laboratory studies, the older, mated females lived
      significantly longer than the virgins. Rather than a "cost of mating," there
      appears to be a "cost of virginity" to female D. melanogaster in the wild.

PMID- 22393527
TI  - Juvenile habitat partitioning and relative productivity in allochronically
      isolated sockeye salmon (Oncorhynchus nerka).
AB  - Allochronic divergence, like spatial isolation, may contribute to population
      diversity and adaptation, however the challenges for tracking habitat utilization
      in shared environments are far greater. Adult Klukshu River (Yukon, Canada)
      sockeye salmon, Oncorhynchus nerka, return as genetically distinct "early" and
      "late" runs. Early and late adult spawning populations (1999 and 2000) and their
      subsequent fry (sampled at 7 sites in 2000 and at 8 sites in 2001 throughout
      Klukshu Lake and River) were genotyped at eight microsatellite loci. Bayesian
      assignment was used to determine the spatial distribution of early versus late
      fry; although intermixed, the distribution of fry significantly differed in
      Klukshu Lake and in the Klukshu River in 2001, based on crosstab analyses. Late
      run fry predominated in Klukshu Lake at all sites, while early-run fry were most
      common in the north and south of Klukshu Lake and in Klukshu River. Early-run
      spawners had significantly higher relative productivity (early life survival)
      than late-run fish (2.9 times more fry produced per early-run adult in 2000, and
      9.2 times more in 2001). This study demonstrates spatial habitat partitioning and
      differences in the contribution of allochronically isolated populations to fry
      abundance, and highlights annual variability that likely contributes to
      recruitment variation.

PMID- 22393528
TI  - Invasion triangle: an organizational framework for species invasion.
AB  - Species invasion is a complex, multifactor process. To encapsulate this
      complexity into an intuitively appealing, simple, and straightforward manner, we
      present an organizational framework in the form of an invasion triangle. The
      invasion triangle is an adaptation of the disease triangle used by plant
      pathologists to help envision and evaluate interactions among a host, a pathogen,
      and an environment. Our modification of this framework for invasive species
      incorporates the major processes that result in invasion as the three sides of
      the triangle: (1) attributes of the potential invader; (2) biotic characteristics
      of a potentially invaded site; and (3) environmental conditions of the site. The
      invasion triangle also includes the impact of external influences on each side of
      the triangle, such as climate and land use change. This paper introduces the
      invasion triangle, discusses how accepted invasion hypotheses are integrated in
      this framework, describes how the invasion triangle can be used to focus research
      and management, and provides examples of application. The framework provided by
      the invasion triangle is easy to use by both researchers and managers and also
      applicable at any level of data intensity, from expert opinion to highly
      controlled experiments. The organizational framework provided by the invasion
      triangle is beneficial for understanding and predicting why species are invasive
      in specific environments, for identifying knowledge gaps, for facilitating
      communication, and for directing management in regard to invasive species.

PMID- 22393530
TI  - Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in
      Alzheimer disease.
AB  - Apolipoprotein E (APOE) genotype is the major genetic risk factor for Alzheimer
      disease (AD); the epsilon4 allele increases risk and the epsilon2 allele is
      protective. In the central nervous system (CNS), apoE is produced by glial cells,
      is present in high-density-like lipoproteins, interacts with several receptors
      that are members of the low-density lipoprotein receptor (LDLR) family, and is a
      protein that binds to the amyloid-beta (Abeta) peptide. There are a variety of
      mechanisms by which apoE isoform may influence risk for AD. There is substantial
      evidence that differential effects of apoE isoform on AD risk are influenced by
      the ability of apoE to affect Abeta aggregation and clearance in the brain. Other
      mechanisms are also likely to play a role in the ability of apoE to influence CNS
      function as well as AD, including effects on synaptic plasticity, cell signaling,
      lipid transport and metabolism, and neuroinflammation. ApoE receptors, including
      LDLRs, Apoer2, very low-density lipoprotein receptors (VLDLRs), and lipoprotein
      receptor-related protein 1 (LRP1) appear to influence both the CNS effects of
      apoE as well as Abeta metabolism and toxicity. Therapeutic strategies based on
      apoE and apoE receptors may include influencing apoE/Abeta interactions, apoE
      structure, apoE lipidation, LDLR receptor family member function, and signaling.
      Understanding the normal and disease-related biology connecting apoE, apoE
      receptors, and AD is likely to provide novel insights into AD pathogenesis and
      treatment.

PMID- 22393531
TI  - Symptomatic and nonamyloid/tau based pharmacologic treatment for Alzheimer
      disease.
AB  - In this work we consider marketed drugs for Alzheimer disease (AD) including
      acetylcholinesterase inhibitors (AChE-Is) and antiglutamatergic treatment
      involving the N-methyl-d-aspartate (NMDA) receptor. We discuss medications and
      substances available for use as cognitive enhancers that are not approved for AD
      or cognitive impairment, and other neurotransmitter-related therapies in
      development or currently being researched. We also review putative therapies that
      aim to slow disease progression by mechanisms not directly related to amyloid or
      tau.

PMID- 22393532
TI  - Vascular normalization as a therapeutic strategy for malignant and nonmalignant
      disease.
AB  - Pathological angiogenesis-driven by an imbalance of pro- and antiangiogenic
      signaling-is a hallmark of many diseases, both malignant and benign. Unlike in
      the healthy adult in which angiogenesis is tightly regulated, such diseases are
      characterized by uncontrolled new vessel formation, resulting in a microvascular
      network characterized by vessel immaturity, with profound structural and
      functional abnormalities. The consequence of these abnormalities is further
      modification of the microenvironment, often serving to fuel disease progression
      and attenuate response to conventional therapies. In this article, we present the
      "vascular normalization" hypothesis, which states that antiangiogenic therapy, by
      restoring the balance between pro- and antiangiogenic signaling, can induce a
      more structurally and functionally normal vasculature in a variety of diseases.
      We present the preclinical and clinical evidence supporting this concept and
      discuss how it has contributed to successful treatment of both solid tumors and
      several benign conditions.

PMID- 22393533
TI  - Tumor endothelial cells.
AB  - The vascular endothelium is a dynamic cellular "organ" that controls passage of
      nutrients into tissues, maintains the flow of blood, and regulates the
      trafficking of leukocytes. In tumors, factors such as hypoxia and chronic growth
      factor stimulation result in endothelial dysfunction. For example, tumor blood
      vessels have irregular diameters; they are fragile, leaky, and blood flow is
      abnormal. There is now good evidence that these abnormalities in the tumor
      endothelium contribute to tumor growth and metastasis. Thus, determining the
      biological basis underlying these abnormalities is critical for understanding the
      pathophysiology of tumor progression and facilitating the design and delivery of
      effective antiangiogenic therapies.

PMID- 22393534
TI  - The HIV-1 epidemic: low- to middle-income countries.
AB  - Low- to middle-income countries bear the overwhelming burden of the human
      immunodeficiency virus type 1 (HIV-1) epidemic in terms of the numbers of their
      citizens living with HIV/AIDS (acquired immunodeficiency syndrome), the high
      degrees of viral diversity often involving multiple HIV-1 clades circulating
      within their populations, and the social and economic factors that compromise
      current control measures. Distinct epidemics have emerged in different
      geographical areas. These epidemics differ in their severity, the population
      groups they affect, their associated risk behaviors, and the viral strains that
      drive them. In addition to inflicting great human cost, the high burden of HIV
      infection has a major impact on the social and economic development of many low-
      to middle-income countries. Furthermore, the high degrees of viral diversity
      associated with multiclade HIV epidemics impacts viral diagnosis and
      pathogenicity and treatment and poses daunting challenges for effective vaccine
      development.

PMID- 22393535
TI  - HIV prevention by oral preexposure prophylaxis.
AB  - The impressive advances in antiretroviral (ARV) therapy of chronic human
      immunodeficiency virus (HIV) infections during the last decade and the
      availability of potent ARV drugs have fueled interest in using chemoprophylaxis
      as a novel HIV prevention strategy. Preexposure prophylaxis (PrEP) refers to the
      use of ARV drugs in HIV-negative persons to prevent HIV infection. The rationale
      for PrEP builds on the success of ARV prophylaxis in preventing mother-to-child
      transmission of HIV and on a large body of animal studies that show the efficacy
      of PrEP against mucosal and parenteral infection. We focus on oral administration
      of ARV drugs for prevention of HIV infection. Identifying an effective
      prophylactic pill that individuals can take outside the setting of sexual
      intercourse precludes the necessity to disclose such use to their partners,
      thereby empowering those who might not be in a position to negotiate with their
      partners. Several human clinical trials evaluating the efficacy of daily regimens
      of the HIV reverse-transcriptase (RT) inhibitors tenofovir disoproxil fumarate
      (TDF) or Truvada (TDF and emtricitabine [FTC]) are under way among high-risk
      populations. The results of one trial among men who have sex with men showed that
      daily Truvada was safe and effective, providing the first support for oral PrEP
      as a prevention strategy. Here we outline the preclinical and clinical research
      on oral PrEP, pharmacologic considerations, and future directions and challenges.

PMID- 22393538
TI  - Modeling Parkinson's disease in primates: The MPTP model.
AB  - The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate models of
      Parkinson's disease (PD) reproduce most, although not all, of the clinical and
      pathological hallmarks of PD. The present contribution presents the possibilities
      offered by the MPTP monkey models of PD to readers with minimal knowledge of PD,
      emphasizing the diversity of species, route and regimen of administration,
      symptoms and pathological features. Readers would eventually find out that there
      is not a single MPTP monkey model of PD but instead MPTP monkey models of PD,
      each addressing a specific experimental need.

PMID- 22393536
TI  - Connecting type 1 and type 2 diabetes through innate immunity.
AB  - The escalating epidemic of obesity has driven the prevalence of both type 1 and 2
      diabetes mellitus to historically high levels. Chronic low-grade inflammation,
      which is present in both type 1 and type 2 diabetics, contributes to the
      pathogenesis of insulin resistance. The accumulation of activated innate immune
      cells in metabolic tissues results in release of inflammatory mediators, in
      particular, IL-1beta and TNFalpha, which promote systemic insulin resistance and
      beta-cell damage. In this article, we discuss the central role of innate immunity
      and, in particular, the macrophage in insulin sensitivity and resistance, beta
      cell damage, and autoimmune insulitis. We conclude with a discussion of the
      therapeutic implications of this integrated understanding of diabetic pathology.

PMID- 22393541
TI  - Prognostic factors in pancreatic cancer.
AB  - Prognostic factors in pancreatic cancer have been a hot topic for the clinical
      pancreatology, and many studies have been involved in the field. The author
      reviewed the pancreatic abstracts of American Pancreas Club 2011, and sumarized
      "highlight" of all the abstracts in prognostic factors in pancreatic cancer.

PMID- 22393540
TI  - Collagen IV in Normal Skin and in Pathological Processes.
AB  - CONTEXT: Type IV collagen is a type of collagen found primarily in the skin
      within the basement membrane zone. The type IV collagen C4 domain at the C
      terminus is not removed in post-translational processing, and the fibers are thus
      link head-to-head, rather than in a parallel fashion. Also, type IV collagen
      lacks a glycine in every third amino-acid residue necessary for the tight
      collagen helix. Thus, the overall collagen-IV conformation is structurally more
      pliable and kinked, relative to other collagen subtypes. These structural
      features allow collagen IV to form sheets, which is the primary structural form
      found in the cutaneous basal lamina. There are six human genes associated with
      collagen IV, specifically COL4A1, COL4A2, COL4A3, COL4A4, COL4A5 and COL4A6. The
      aim of this review is to highlight the significance of this protein in normal
      skin, and in selected diseases. RESULTS: The alpha 3 protein constituent of type
      IV collagen is thought to be the antigen implicated in Goodpasture's syndrome,
      wherein the immune system attacks the basement membranes of the renal glomeruli
      and pulmonary alveoli. In addition, mutations to the genes coding for type IV
      collagen lead to the Alport syndrome. Furthermore, autoantibodies directed
      against denatured human type IV collagen have been described in rheumatoid
      arthritis, scleroderma, and SLE. Structural studies of collagen IV have been
      utilized to differentiate between subepidermal blistering diseases, including
      bullous pemphigoid, acquired epidermolysis bullosa, anti-epiligrin cicatricial
      pemphigoid, and bullous lupus erythematosus. Collagen IV is also of importance in
      wound healing and in embryogenesis. CONCLUSIONS: Pathological studies have
      demonstrated that minor structural differences in collagen IV can lead to
      distinct, clinically different diseases.

PMID- 22393537
TI  - Breakdown in peripheral tolerance in type 1 diabetes in mice and humans.
AB  - Type 1 Diabetes (T1D), also called juvenile diabetes because of its classically
      early onset, is considered an autoimmune disease targeting the insulin-producing
      beta cells in the pancreatic islets of Langerhans. T1D reflects a loss of
      tolerance to tissue self-antigens caused by defects in both central tolerance,
      which aims at eliminating potentially autoreactive lymphocytes developing in the
      thymus, and peripheral tolerance, which normally controls autoreactive T cells
      that escaped the thymus. Like in other autoimmune diseases, the mechanisms
      leading to T1D are multifactorial and depend on a complex combination of genetic,
      epigenetic, molecular, and cellular elements that result in the breakdown of
      peripheral tolerance. In this article, we discuss the contribution of these
      factors in the development of the autoimmune response targeting pancreatic islets
      in T1D and the therapeutic strategies currently being explored to correct these
      defects.

PMID- 22393539
TI  - Leucine-rich repeat kinase 2 for beginners: six key questions.
AB  - There has been intense interest in leucine-rich repeat kinase 2 (LRRK2) since
      2004, when mutations in the LRRK2 gene were discovered to cause dominantly
      inherited Parkinson's disease (PD). This article will address six basic questions
      about LRRK2 biology as it relates to PD, with particular emphasis on its
      discovery, current concepts of its physiological and pathological functions, and
      the strategies being used to discover how LRRK2 dysfunction causes PD.

PMID- 22393542
TI  - Cesarean section in morbidly obese parturients: practical implications and
      complications.
AB  - The prevalence of obesity has reached pandemic proportions across nations. Morbid
      obesity has a dramatic impact on pregnancy outcome. Cesarean section in these
      women poses many surgical, anesthetic, and logistical challenges. In view of the
      increased risk of cesarean delivery in morbidly obese women, the practical
      implications and complications are reviewed in this article. A Medline search was
      conducted to review the recent relevant articles in english literature on
      cesarean section in morbidly obese women. The types of incisions and techniques
      used during cesarean delivery, intra-operative and postpartum complications,
      anesthetic and logistical issues, maternal morbidity and mortality were reviewed.
      Morbidly obese women with a body mass index (BMI >40 kg/m(2) are at increased
      risk of pregnancy complications and a significantly increased rate of cesarean
      delivery. Low transverse skin incisions and transverse uterine incisions are
      definitely superior and must be the first option. Closure of the subcutaneous
      layer is recommended, but the placement of subcutaneous drains remains
      controversial. Thromboprophylaxis adjusted to body weight and prophylactic
      antibiotics help in reducing postpartum morbidity. Morbidly obese women are at
      increased risk of postpartum infectious morbidity. Weight reduction in the
      postpartum period and thereafter must be strongly encouraged for optimal future
      pregnancy outcomes and well-being.

PMID- 22393543
TI  - The Reason for Regimen Change Among HIV/AIDS Patients Initiated on First Line
      Highly Active Antiretroviral Therapy in Southern Ethiopia.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) has markedly decreased
      the morbidity and mortality due to HIV disease. However, toxicities, comorbidity,
      pregnancy, and treatment failure, among others, would result in frequent initial
      HAART regimen change. AIM: The study was designed to assess the causes of initial
      highly active antiretroviral therapeutic regimen changes among patients on HAART.
      MATERIALS AND METHODS: The study was conducted using a retrospective institution
      based study, by reviewing the patient information sheet and physician diagnosis
      cards. Patient cards that showed a change in the initial treatment regimen were
      assessed and analyzed, to identify the common reason that resulted in a change
      from the initial treatment regimen. The data was analyzed using SPSS version
      16.0. RESULTS: A total of 340 patient cards were assessed. The majority of the
      patients (69.29%) were females. The most common first regimen, before the first
      switch, was stavudine / lamivudine / nevirapine (D4T/3TC/NVP) (54.70%) and
      stavudine / lamivudine / Efavirenz (D4T/3TC/EFV) (20.88%). The main reasons for
      modification were toxicity, comorbidity, pregnancy, and treatment failure. The
      main types of toxicities observed were peripheral neuropathy (36.52%), rash
      (17.83%), and anemia (17.39%). CONCLUSION: Toxicity was the main reason for the
      modification of initial HAART among the study population. Efavirenz-based
      regimens had the lowest hazard for change relatively, except in pregnancy-related
      cases.

PMID- 22393544
TI  - Medicine Vendors: Self-medication Practices and Medicine Knowledge.
AB  - BACKGROUND: Medicine vendors fill the gap created by inadequate skilled
      professionals required for medicine procurement, storage, and distribution in
      developing countries. AIM: To evaluate self-medication practice and medicine
      knowledge among medicine vendors and to determine if a relationship exists
      between both. MATERIALS AND METHODS: A descriptive, cross-sectional study was
      conducted, using a pretested questionnaire on 236 medicine vendors in Jos,
      Nigeria, sampled through a two-stage stratified design. Data collected were
      analyzed using the Statistical Package for Social Sciences version 16, and the
      chi-square test was used to determine the association between variables. RESULTS:
      Self-medication was common (75.4%) among respondents and was not associated
      (P>0.05) with any of the demographic characteristics studied. The classes of
      medicines commonly used by respondents for self-medication were analgesics
      (31.4%), anti-malarials (22.6%), multivitamins (17.7%), and antibiotics (11.25%).
      A knowledge assessment test revealed that only 34.3% of the respondents had
      adequate knowledge. There was no significant (P>0.05) relationship between self
      medication practice and medicine knowledge, among the respondents. However, the
      medicine knowledge scores were significantly (P<0.05) associated with holding a
      certificate in health sciences, years of experience, and the place of practice of
      the medicine vendors. CONCLUSION: The present study demonstrated that self
      medication practice was high and inadequate medicine knowledge existed among
      respondents.

PMID- 22393545
TI  - Prevalence of nosocomial wound infection among postoperative patients and
      antibiotics patterns at teaching hospital in Sudan.
AB  - BACKGROUND: Postoperative nosocomial infections remain a major problem in health
      care facilities, resulting in extended length of stay, substantial morbidity and
      mortality, high excess of cost, and less frequent cause of death in the surgical
      patient. AIMS: To determine the prevalence of aerobic nosocomial pathogens among
      patients with postoperative wound infections at Gadarif state which located in
      Eastern part of Sudan. MATERIALS AND METHODS: 109 wound swabs were collected from
      patients who had developed postoperative wound infection. Conventional technique
      for isolation of bacteria was applied with analytical profile index (API system)
      for identification to confirm primary and secondary isolates. Antibiotics
      susceptibility was applied for all isolated bacteria. RESULTS: Aerobic bacterial
      isolates were S. aureus (n=55, 55.0%), P. mirabilis (n=35, 35.0%), E. coli (n=5,
      5.0%), Ps. aeruginosa (n=3, 3.0%), and Pr. vulgaris (n=2, 2.0%). The prevalence
      rate of hospital acquired infection were 25.23% CONCLUSION: The highest
      prevalence rate of nosocomial postoperative wound infection, in Sudan was due to
      poor antibiotic selection, for prophylaxis during and after surgery and increased
      level of contamination in most part of the hospital.

PMID- 22393546
TI  - Perforated duodenal ulcer in high risk patients: is percutaneous drainage
      justified?
AB  - BACKGROUND: Conservative treatment was recommended as the treatment of choice in
      perforated acute peptic ulcer. Here, we adjunct percutaneous peritoneal drainage
      with nonoperative conservative treatment in high risk elderly patients with
      perforated duodenal ulcer. AIM: The work was to study the efficacy of
      percutaneous peritoneal drainage under local anesthesia supported by conservative
      measures in high risk elderly patients, according to the American Society of
      Anesthesiologists grading, with perforated duodenal ulcer. PATIENTS AND METHODS:
      Twenty four high risk patients with age >65 years having associated medical
      illness with evidence of perforated duodenal ulcer. RESULTS: The overall
      morbidity and mortality were comparable with those treated by conservative
      measures alone. CONCLUSION: In high risk patients with perforated peptic ulcer
      and established peritonitis, percutaneous peritoneal drainage under local
      anesthesia seems to be effective with least operative trauma and mortality rate.

PMID- 22393547
TI  - Demographic Factors Associated with Insecticide Treated Net use Among Nigerian
      Women and Children.
AB  - BACKGROUND: Malaria constitutes a major health problem, with children and
      pregnant women being the most vulnerable to its morbidity and mortality. AIM: To
      determine the demographic factors associated with the use of insecticide-treated
      nets among children and pregnant women in Nigeria. MATERIALS AND METHODS: The
      study was based on data drawn from the Nigeria Demographic and Health Survey 2008
      on the use of insecticide-treated nets among women and children. The survey was
      conducted in 34070 households and a total of 10,724 women aged 15-49 years
      participated in the survey. Data were entered into Minitab version 15 and the chi
      square test for independence was performed to show association between variables.
      RESULTS: The results revealed that 49.8% of children and 44% of pregnant women
      present in households that owe insecticide-treated nets slept under them on the
      night before the survey. Sleeping under an insecticide-treated nets among
      children was associated with (P<0.05) the age of a child, geopolitical zone, and
      wealth quintile while the use of insecticide-treated nets among pregnant women
      was associated with the education level and wealth quintile of households.
      CONCLUSION: The study demonstrated that some demographic factors are associated
      with the use of ITNs among children and pregnant women in Nigeria.

PMID- 22393548
TI  - Assessment of causes and patterns of recurrent varicose veins after surgery.
AB  - BACKGROUND: Varicose vein surgery is characterized by high recurrence rate of 60%
      after 5 years of follow-up observation, and this is a disappointing finding, both
      for the patient and surgeon. AIM: To identify the possible causes and patterns of
      recurrent varicose veins. MATERIALS AND METHODS: 92 patients with recurrent
      varicose veins were enrolled in this study. Full detailed history, examination,
      and investigations were done. RESULTS: 30 patients had recurrence after
      saphenofemoral disconnection, 22 patients with recurrence after saphenofemoral
      disconnection and stripping below knee, 28 patients recurrence after
      saphenofemoral disconnection with stripping above knee and 12 patients recurrence
      after sapheno-popliteal disconnection with stripping. The double great saphenous
      veins, neovascularization and deep venous thrombosis before and after surgery
      were the most observed patterns of recurrence. The anatomical patterns of
      recurrence were more in leg then both leg and thigh pattern. CONCLUSION:
      Saphenofemoral ligation with below knee stripping has the least frequency of
      recurrence, while Trendlenberg operation alone has the highest.

PMID- 22393549
TI  - Eight Years Follow-up of a Case with Idiopathic Pulmonary Hemosiderosis After
      Corticosteroid Therapy.
AB  - Idiopathic pulmonary hemosiderosis is characterized by recurrent episodes of
      alveolar hemorrhage, hemoptysis, and secondary iron deficiency anemia with
      unknown etiology. It generally emerges in childhood and adolescence periods but
      rarely found in adulthood. Definite diagnosis is established by appearing the
      hemosiderin-laden macrophages at sputum, bronchoalveolar lavage, or open lung
      biopsy. We reported a male patient who was born in 1975, expectorated blood since
      1995, and was diagnosed in 1998. He received many blood replacements. He admitted
      to our clinic in 2003 with complaints of coughing up blood, shortness of breath,
      and tiredness. We gave the corticosteroid therapy to patient for 6-month period.
      After treatment, the patient did not have any complaints. Clinicians should keep
      in mind that idiopathic pulmonary hemosiderosis may differ in localization on
      chest X-ray and corticosteroid treatment should be started when diagnosis is
      established.

PMID- 22393550
TI  - It takes a village.

PMID- 22393551
TI  - The work-up for mixed hyperlipidemia: a case study.
AB  - This case demonstrates that a history, physical exam, and laboratory studies are
      all needed to determine if the disorder is primary, secondary, or both.

PMID- 22393552
TI  - Menopause management: how you can do better.
AB  - Let patients know that hot flashes, vaginal dryness, and other common menopausal
      symptoms can be treated successfully with hormonal and nonhormonal agents.

PMID- 22393553
TI  - ACIP immunization update.
AB  - Males ages 11 to 12 years should routinely receive quadrivalent vaccine against
      human papillomavirus; patients through age 59 years who have diabetes should
      receive HBV vaccine routinely.

PMID- 22393554
TI  - PURLs: BP meds: this simple change improves outcomes.
AB  - For patients with uncontrolled hypertension, a switch to bedtime dosing is
      advisable.

PMID- 22393555
TI  - PURLs: Counseling is a must with this smoking cessation aid.
AB  - For many smokers, the benefits of quitting will outweigh the risks associated
      with varenicline.

PMID- 22393556
TI  - Acral papular rash in a 2-year-old boy.

PMID- 22393557
TI  - Clinical inquiry. How best to diagnose iron-deficiency anemia in patients with
      inflammatory disease?

PMID- 22393558
TI  - Clinical inquiry: Is high-dose oral B12 a safe and effective alternative to a B12
      injection?

PMID- 22393559
TI  - Clinical inquiry: What nutritional deficiencies and toxic exposures are
      associated with nail changes?

PMID- 22393560
TI  - When a fetus survives methotrexate exposure.
AB  - Whether the drug is used for a medical abortion that ultimately fails or for
      other conditions when pregnancy is unsuspected, your counsel could be a patient's
      only resource.

PMID- 22393561
TI  - Fatty liver disease in type 2 diabetes: common and often unmanaged.
AB  - This study of patients with type 2 diabetes in a large rural clinic showed that
      abnormal liver function tests do not usually lead to diagnostic imaging studies.

PMID- 22393562
TI  - Preface.

PMID- 22393563
TI  - The association of Aggregatibacter actinomycetemcomitans with preeclampsia in a
      subset of Japanese pregnant women.
AB  - AIM: To determine whether periodontitis and three prominent members of the
      periodontal flora are associated with the development of preeclampsia
      (hypertension plus proteinuria) Materials and Methods: The samples were composed
      of 127 systemically healthy women. Within 5 days after labour, clinical
      periodontal parameters and Aggregatibacter actinomycetemcomitans, Porphyromonas
      gingivalis and Prevotella intermedia in subgingival plaque were evaluated.
      Maternal serum IgG antibody specific for each bacteria was determined by enzyme
      linked immunosorbent assay. Multivariate logistic regression analysis was used to
      control for confounders (maternal age, body mass index before pregnancy, parity,
      and smoking). RESULTS: Eighteen women were affected with preeclampsia. The number
      of A.actinomycetemcomitans was shown to be significantly associated with
      preeclampsia in the logistic regression model (odds ratio; 1.7, 95% confidence
      interval; 1.1-2.7). There were statistically significant differences between the
      preeclamptic and control groups in body mass index before pregnancy, pre-term
      birth and low birthweight (respectively, p = 0.014, p = 0.010 and p < 0.0001). We
      found no statistically significant association between preeclampsia and
      periodontal clinical parameters or the presence of periodontitis. CONCLUSION: In
      systemically healthy pregnant women, our findings suggested that the levels of
      maternal subgingival A. actinomycetemcomitans DNA were elevated in preeclamptic
      women.

PMID- 22393564
TI  - Door-to-VAD time: an expedient management strategy for cardiogenic shock.
AB  - PURPOSE OF REVIEW: Emerging devices are now providing full hemodynamic support
      and may improve survival in patients who present with cardiogenic shock. This
      manuscript will present the framework strategy for utilizing current advancements
      in temporary device therapy for acutely decompensated patients with cardiogenic
      shock, as a stabilizing bridge-to-decision (BTD) modality. We identify criteria
      for the clinical presentation of cardiogenic shock and a list of factors that
      suggest inferior outcomes. RECENT FINDINGS: Cardiogenic shock continues to be
      associated with significant morbidity and mortality. The observed poor outcomes
      are usually impacted by delayed recognition and limited pharmacologic options.
      Initial therapeutic responses are often temporarily successful, but fail to
      adequately resuscitate many patients who ultimately die of multiorgan system or
      septic deaths. SUMMARY: We will describe essential clinical components to assist
      in identifying such patients for short-term circulatory support as a BTD for
      advanced durable ventricular assist devices. Improved outcomes of patients with
      cardiogenic shock may be achieved by both early clinical recognition and early
      strategic implementation of sustainable temporary circulatory support.

PMID- 22393565
TI  - A Bayesian network meta-analysis on comparisons of enamel matrix derivatives,
      guided tissue regeneration and their combination therapies.
AB  - AIMS: Guided tissue regeneration (GTR) and enamel matrix derivatives (EMD) are
      two popular regenerative treatments for periodontal infrabony lesions. Both have
      been used in conjunction with other regenerative materials. We conducted a
      Bayesian network meta-analysis of randomized controlled trials on treatment
      effects of GTR, EMD and their combination therapies. MATERIAL AND METHODS: A
      systematic literature search was conducted using the Medline, EMBASE, LILACS and
      CENTRAL databases up to and including June 2011. Treatment outcomes were changes
      in probing pocket depth (PPD), clinical attachment level (CAL) and infrabony
      defect depth. Different types of bone grafts were treated as one group and so
      were barrier membranes. RESULTS: A total of 53 studies were included in this
      review, and we found small differences between regenerative therapies which were
      non-significant statistically and clinically. GTR and GTR-related combination
      therapies achieved greater PPD reduction than EMD and EMD-related combination
      therapies. Combination therapies achieved slightly greater CAL gain than the use
      of EMD or GTR alone. GTR with BG achieved greatest defect fill. CONCLUSION:
      Combination therapies performed better than single therapies, but the additional
      benefits were small. Bayesian network meta-analysis is a promising technique to
      compare multiple treatments. Further analysis of methodological characteristics
      will be required prior to clinical recommendations.

PMID- 22393566
TI  - Management of sudden cardiac death risk in the very early postmyocardial
      infarction period.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize the numerous recent
      studies assessing the strategies to manage the increased risk of sudden cardiac
      death (SCD) early after a myocardial infarction (MI). RECENT FINDINGS: Early
      after a MI, the risk of SCD is high. Several trials have been completed in
      attempt to identify and treat patients at increased risk for SCD early post-MI.
      These trials have evaluated QT interval, cardiac autonomic modulation, signal
      averaged ECG, microvolt T-wave alternans, electrophysiology testing and early
      measurement of the left-ventricular ejection fraction (LVEF). Although some of
      these parameters were associated with increased total mortality, no parameter
      provided adequate predictive accuracy of increased risk for SCD that could guide
      use of an implantable cardiac defibrillator (ICD). SUMMARY: Other than LVEF
      measured more than 40 days post-MI (consistent with current ICD guidelines),
      there is no noninvasive or invasive test that reliably predicts the risk for SCD
      or that can guide empiric ICD implantation soon after a MI. In the early post-MI
      period, therefore, the goal is to maximize medical therapy and revascularization.
      The LVEF should then be measured no sooner than 40 days post-MI and, if the LVEF
      is 35% or less, the patient should be considered for ICD implantation.

PMID- 22393567
TI  - Current world literature.

PMID- 22393568
TI  - Presentations: Billboard science.

PMID- 22393569
TI  - Retraction notice to "Comparative proteomics reveals deficiency of NHE-1 (Slc9a1)
      in RBCs from the beta-adducin knockout mouse model of hemolytic anemia" [Blood
      Cells Mol. Dis. 47 (2011) 85-94].

PMID- 22393570
TI  - Postparturient haemoglobinuria with low blood phosphate in a dairy herd.

PMID- 22393571
TI  - China's invisible burden of foodborne illness.

PMID- 22393572
TI  - Antidepressant-suicide link in children questioned.

PMID- 22393573
TI  - Nigeria's lead poisoning crisis could leave a long legacy.

PMID- 22393574
TI  - Smoking may seriously affect your skeleton.

PMID- 22393575
TI  - Abstracts of the 46th Annual Scientific Meeting of the Vascular Society of Great
      Britain and Ireland. November 24-26, 2011. Edinburgh, Scotland.

PMID- 22393576
TI  - Abstracts of the American Society for Reproductive Medicine (ASRM) 67th Annual
      Meeting. October 15-19, 2011. Orlando, Florida, USA.

PMID- 22393577
TI  - [Hospital information system and epidemiology. Abstracts of Adelf-Emois
      Colloquium. March 12-13, 2012. Dijon, France].

PMID- 22393578
TI  - Abstracts of the Annual Meeting of the Association of Academic Physiatrists. Las
      Vegas, Nevada, USA. February 28-March 3, 2012.

PMID- 22393579
TI  - Abstracts of the 8th Global Arthritis Research Network (GARN) Meeting and 1st Bio
      Rheumatology International Congress (BRIC). November 14-16, 2011. Tokyo, Japan.

PMID- 22393580
TI  - What kind of laws does food safety need? Lessons from poisonous drinks containing
      plasticizer di-(2-ethylhexyl)phthalate.

PMID- 22393581
TI  - Plasticizer event in Taiwan.

PMID- 22393582
TI  - Strong reciprocity is real, but there is no evidence that uncoordinated costly
      punishment sustains cooperation in the wild.
AB  - I argue in my target article that field evidence does not support the costly
      punishment hypothesis. Some commentators object to my reading of the evidence,
      while others agree that evidence in favour of costly punishment is scant. Most
      importantly, no rigorous measurement of cost-benefit ratios in the field has been
      attempted so far. This lack of evidence does not rule out costly punishment as a
      cause of human cooperation, but it does pre-empt some overconfident claims made
      in the past. Other commentators have interpreted my article as an anti
      experimental pamphlet or as a flat denial of the existence of pro-social motives-
      which it was not intended to be. While we have enough data to establish the
      existence (and theoretical relevance) of strong reciprocity motives, I argue in
      this response that their efficacy (and policy relevance) has not been
      demonstrated.

PMID- 22393584
TI  - Assessment of the health impacts of particulate matter characteristics.
AB  - While numerous studies have demonstrated that shortterm exposure to particulate
      matter (PM*) is associated with adverse health effects, the characteristics of PM
      that cause harm are not well understood, and PM toxicity may vary by its chemical
      composition. This study investigates whether spatial and temporal patterns in PM
      health effect estimates based on total mass can be explained by spatial and
      temporal heterogeneity in the chemical composition of the particles. A database
      of 52 chemical components of PM with an aerodynamic diameter < or = 2.5 pm
      (PM2.5) was constructed for 187 U.S. counties, for 2000 through 2005, based on
      data from U.S. Environmental Protection Agency (U.S. EPA) monitoring networks.
      Components that covary with PM2.5 total mass and/or are large contributors to
      PM2.5, total mass were identified using actual and seasonally detrended data.
      Using Bayesian hierarchical modeling, seasonal and temporal variation in PM2.5
      and the risk of total, cardiovascular, and respiratory hospital admissions were
      investigated for persons > or = 65 years in 202 U.S. counties for 1999 through
      2005. Seasonal variation was investigated using three model structures with
      different underlying assumptions about the relationship between PM2.5 and
      hospitalizations. The findings of this study indicate higher effects in winter
      for both causes of hospitalization, and higher effects in the Northeast for
      cardiovascular admissions, although 53% of the counties were in this region.
      Higher PM2.5 effect estimates for cardiovascular or respiratory hospitalizations
      were observed in seasons and counties with a higher PM2.5 content of nickel (Ni),
      vanadium (V), or EC. Mortality effect estimates for PM with an aerodynamic
      diameter < or = 10 pm (PM10) were higher in seasons and counties with higher
      PM2.5 Ni content. The association between the Ni content of PM2.5 and effect
      estimates for cardiovascular hospitalization was robust to adjustment by EC, V,
      or both EC and V. An interquartile range (IQR) increase in the fraction of PM2.5
      that is Ni was associated with a 14.9% (PI, 3.4-26.4) increase in the relative
      rates of cardiovascular hospital admissions associated with PM2.5 total mass
      adjusted for EC and V. No associations were observed between PM total mass health
      effect estimates and community-level variables for socioeconomic status, racial
      composition, or urbanicity. Communities with a higher prevalence of central AC
      had lower PM2.5 effect estimates for cardiovascular hospital admissions. The
      findings of this study indicate strong spatial and temporal variation in the
      chemical composition of the particle mixture and in the regional and seasonal
      variation in health effect estimates for PM2.5 total mass. The chemical
      composition of particles partially explained the heterogeneity of effect
      estimates. Observed associations could be related to the components themselves,
      to other components, or to a combination of components that share similar
      sources. The findings do not exclude the possibility that other components or
      characteristics of PM are harmful. The limitations of this study include the use
      of community-level aggregated data for exposure and for the variables used to
      investigate alternate hypotheses. Also, particle components and chemical forms
      (e.g., ammonium sulfate) not measured in the U.S. EPA database were not included.
      PM10 results in particular should be viewed with caution as the time frame of
      measurement and PM size fraction are different for the chemical composition and
      health effects data. A better understanding of the particular chemical components
      or sources that are most harmful to health can help decision-makers develop more
      targeted air pollution regulations and can aid in understanding the biological
      mechanisms by which air pollution-related health effects occur, thereby informing
      future research.

PMID- 22393585
TI  - [The expression of GABA(A) receptor alpha1 and GABA(B) receptor 1 in medulla
      oblongata solitary nucleus and ambiguous nucleus in the cases of tramadol
      intoxication].
AB  - OBJECTIVE: To observe the expression of GABA(A) receptor alpha1 (GABA(A)alpha1)
      and GABA(B) receptor 1 (GABA(B)1) in human medulla oblongata solitary nucleus and
      ambiguous nucleus due to tramadol-induced death. METHODS: GABA(A)alpha1 and
      GABA(B)1 were detected by immunohistochemical SP method in tramadol-induced death
      group and control group. All results were evaluated by images analysis system.
      RESULTS: Low expression of GABA(A)alpha1 and GABA(B)1 were detected in solitary
      nucleus and ambiguous nucleus in the control brain tissue. In cases of tramadol
      induced death, the expression of GABA(A)alpha1 and GABA(B)1 significantly
      increased. CONCLUSION: The mechanism of tramadol intoxication death could be
      caused by respiratory depression induced by over-expression of GABA(A)alpha1 and
      GABA(B)1 in medulla oblongata solitary nucleus and ambiguous nucleus.

PMID- 22393583
TI  - Solubilization of beclomethasone dipropionate in sterically stabilized
      phospholipid nanomicelles (SSMs): physicochemical and in vitro evaluations.
AB  - BACKGROUND: The local treatment of lung disorders such as asthma and chronic
      obstructive pulmonary disease via pulmonary drug delivery offers many advantages
      over oral or intravenous routes of administration. This is because direct
      deposition of a drug at the diseased site increases local drug concentrations,
      which improves the pulmonary receptor occupancy and reduces the overall dose
      required, therefore reducing the side effects that result from high drug doses.
      From a clinical point of view, although jet nebulizers have been used for aerosol
      delivery of water-soluble compounds and micronized suspensions, their use with
      hydrophobic drugs has been inadequate. AIM: To evaluate the feasibility of
      sterically stabilized phospholipid nanomicelles (SSMs) loaded with beclomethasone
      dipropionate (BDP) as a carrier for pulmonary delivery. METHODS: 1,2-Distearoyl
      sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 5000) polymeric
      micelles containing BDP (BDP-SSMs) were prepared by the coprecipitation and
      reconstitution method, and the physicochemical and in vitro characteristics of
      BDP-SSMs were investigated. RESULTS: BDP-SSMs were successfully prepared with a
      content uniformity and reproducibility suitable for pulmonary administration. The
      maximum solubility of BDP in SSMs was approximately 1300 times its actual
      solubility. The particle size and zeta potential of BDP-SSMs were 19.89 +/- 0.67
      nm and -28.03 +/- 2.05 mV, respectively. The SSMs system slowed down the release
      of BDP and all of the aerodynamic values of the aerosolized rehydrated BDP-SSMs
      were not only acceptable but indicated a significant level of deposition in the
      lungs. CONCLUSION: The SSM system might be an effective way of improving the
      therapeutic index of nebulized, poorly soluble corticosteroids.

PMID- 22393586
TI  - [Effects of ketamine on proliferation and apoptosis of pheochromocytoma cell].
AB  - OBJECTIVE: To explore the effect of ketamine on adrenal pheochromocytoma (PC12)
      cell proliferation inhibition and induction of apoptosis and its mechanism.
      METHODS: PC12 cells of rats were models for dopaminergic neuron. PC12 cells were
      cultured with ketamine at concentrations of 0.9, 1.2, 1.5, 1.8 and 2.1 mmol/L,
      respectively. The cell viability was measured by MTT method after incubation at
      12, 24, 48 and 72h. Hoechst stain was used to observe the morphological changes
      of apoptosis. PC12 cells cultured after 48 h with different concentrations of
      ketamine were selected to detect apoptotic rate using flow cytometry and detect
      the expression of bax and bcl-2 proteins using Western blotting. RESULTS: For
      different concentrations of ketamine, vitality of PC12 cells significantly
      decreased with increase of the incubation time. Apoptosis was obviously observed
      using Hoechst staining. Flow cytometry showed that apoptosis rates significantly
      increased with increasing ketamine concentrations. CONCLUSION: Ketamine can
      inhibit the proliferation of PC12 cell by inducing apoptosis of the PC12 cell in
      a concentrations-dependent manner. The underlying mechanism may be related to
      promoting the expression of bax and inhibiting the expression of bcl-2 in the
      cells.

PMID- 22393587
TI  - [Homer protein expression after focal brain contusion in rats].
AB  - OBJECTIVE: To investigate Homer protein expression after focal brain contusion
      and explore the relationship between expression and injury time. METHODS: Focal
      brain contusion in rats was established and Homer protein expression in brain at
      different injury intervals after contusion was detected by immunohistochemistry
      and Western blotting. RESULTS: A small amount of Homer positive expression cells
      were detected in control group, sham operated group and experimental group (0.5 h
      after contusion). The amount of Homer positive expression cells increased after 3
      h and reached peak 12 h after contusion. The amount of positive cells continued
      to decrease 1 d after contusion and to the base level 7 d after contusion. Homer
      protein expression based on immunohistochemistry and Western blotting had
      statistical difference among adjacent groups. CONCLUSION: Expression of Homer
      protein near the focal contusion area shows time dependence after brain contusion
      in rats.

PMID- 22393588
TI  - [Identifying malingering symptoms of balance disorders by computerized dynamic
      posturography].
AB  - OBJECTIVE: To develop an objective criteria with computerized dynamic
      posturography (CDP) for identification of non-organic or malingering symptoms of
      balance disorders. METHODS: One hundred and four normal subjects were instructed
      to feign balance disturbance after naturally performing on CDP. Paired t-test was
      used to determine if there was significant difference of CDP equilibrium scores
      between normal and malingering performance. The CDP records including raw curve
      of 50 subjects were critically evaluated by previously published seven criteria
      in indicating malingering performance. If the sensitivity of a criterion was
      greater than 90%, it would be accepted as our laboratory's identifying criterion.
      The CDP records of remaining 54 subjects were used to test the sensitivity and
      specificity of the accepted criteria. RESULTS: There were statistically
      significant differences of CDP equilibrium scores between normal and malingering
      performance (P < 0.01). The mean equilibrium scores of malingering performance
      were lower than that of normal performance. The sensitivity and specificity of
      our criteria for identifying malingerers were 92.5% and 98.2%, respectively.
      CONCLUSION: It is necessary to identify malingering performance before analyzing
      the CDP equilibrium scores. Our identifying criteria of malingerers seems to be
      quite useful and accurate.

PMID- 22393589
TI  - [Skeletal age estimation of sternal end of clavicle in Sichuan Han nationality
      youth using thin-section computed tomography].
AB  - OBJECTIVE: To explore the growth status of epiphysis of sternal end of clavicle
      using thin-section computed tomography (CT) and to study the relationship between
      the status and the chronological age of Sichuan Han nationality youth. METHODS:
      According to the Schmeling's report and the age range of our samples, the
      ossification status of medial clavicle epiphysis was classified as four stages.
      CT films of 565 patients between 15 and 25 years were studied based on the
      classification and analyzed statistically. RESULTS: There was no statistical
      difference between the sexes (P > 0.05). The calculated empiric distribution
      function showed that 100% of stage 1 patients were under 18 years, 75% of stage 2
      patients were under 18 years, 94.5% of stage 3 patients were over 18 years, and
      100% of the stage 4 patients were over 20 years, respectively. CONCLUSION: The
      ossification of medial epiphysis of the clavicle for those around 18 years has
      certain regular. These characteristics can be used for forensic identification of
      the skeletal age, especially 18 years, which is the criminal responsibility age.

PMID- 22393590
TI  - [Calculation of the avuncular index].
AB  - OBJECTIVE: To introduce the method of avuncular index (AI) calculation. METHODS:
      Identity by decent coefficient, coancestry coefficient and AI law were employed
      in identification of uncle-niece relationship, when autosomal STR loci were
      detected to determine controversial uncle-niece relationship. RESULTS: The
      results of AI calculation were coincidental using identity by descent coefficien,
      coancestry coefficient and AI law. CONCLUSION: The results are coincidental using
      three methods in the different situations. AI index is higher with participation
      of children's mother.

PMID- 22393591
TI  - [Determination of 24 elements in human hair by ICP-MS using microwave digestion].
AB  - OBJECTIVE: To establish an inductively coupled plasma-mass spectrometry (ICP-MS)
      method for determination of 24 elements in human hair. METHODS: The samples were
      digested with microwave digestion instrument. ICP-MS was applied to determine 24
      elements in human hair using indium (115In) as an internal standard. The
      established method was applied to determine element concentration in normal group
      (56 samples) and heroin abuse group (10 samples). RESULTS: The limits of
      detection ranged from 0.000 3 microg/g to 10.14 microg/g. Measured value of the
      standard materials were basically consistent with the standard value. The
      contents of magnesium, gallium and barium in hair of heroin addicts decreased
      after rehabilitation treatment. CONCLUSION: The method is sensitive and accurate
      for determination of 24 elements in human hair.

PMID- 22393592
TI  - [Determination of propofol in human blood by GC-MS].
AB  - OBJECTIVE: To establish a gas chromatography-mass spectrometry (GC-MS) method for
      determination of propofol in human blood. METHODS: Propofol and 2-(tert-Butyl)
      4,6-dimethylphenol (internal standard) were isolated from human blood samples
      with liquid-liquid ether extraction. The organic layer was collected after
      centrifugation and dried using the water bath. The extracted residue was analyzed
      by GC-MS. RESULTS: Propofol and the internal standard showed a good separation
      with a good linear concentration ranged from 0.02 to 10 microg/mL in blood. The
      linear function was y = 0.313 6 x-0.006 8 with the correlation coefficient of
      0.9997. The precision of intra-day and inter-day were less than 4.8% and the
      lower limit of detection of propofol was 0.005 microg/mL. Propofol concentration
      of blood was 0.14 microg/mL using this method in the practice work. CONCLUSION:
      The GC-MS method is rapid, sensitive, reliable and suitable for qualitative and
      quantitative analysis propofol of blood in forensic toxicological analysis and
      clinical drug monitoring.

PMID- 22393594
TI  - [Forensic clinical analysis on 25 cases of traumatic cerebral infarction].
AB  - OBJECTIVE: To investigate characteristics of forensic clinical identification on
      traumatic cerebral infarction(TCI). METHODS: Twenty-five cases of TCI were
      analyzed retrospectively, including the general situation, location of infarction
      and clinical feature. RESULTS: TCI occurred primarily in children and elderly.
      All the cases had definite cerebral trauma which was located mainly in the
      regions of basal ganglia-internal capsule, frontal, temporal and parietal
      cerebral cortex. CONCLUSION: The consequence of TCI has direct correlation with
      location of cerebral infarction. More attention should be paid to this issue in
      forensic practice.

PMID- 22393593
TI  - [Pathological characteristics of sudden death caused by coronary thrombosis].
AB  - OBJECTIVE: To explore medico-legal characteristics of sudden death caused by
      coronary heart disease combined with coronary thrombosis. METHODS: Ninety-six
      cases of sudden death caused by coronary heart disease were collected and divided
      into two groups: thrombus positive and thrombus negative groups. The time onset,
      induction and pathological features of coronary artery disease were analyzed.
      RESULTS: Two groups showed man-dominant population. There were no statistical
      significant differences in season, circadian rhythm and induction factor. The
      thrombus positive group (age < 40) showed a higher disease incidence. Heart
      weight and degree of coronary stenosis were lower in thrombus positive group.
      However, there was no statistical difference in the number of atherosclerotic
      coronary arteries (> or = 2), the length of coronary lesions and myocardial
      infarct. But thrombosis positive group showed lower tendency. CONCLUSION: Two
      groups are man-dominant population and similar induction factor, lesion position,
      mechanism of death. But thrombus positive group appeared more in a younger
      population and the degree of coronary stenosis is milder than thrombus negative
      group. Forensic pathologists should pay more attention to these characteristics
      in death investigation.

PMID- 22393595
TI  - [DNA extraction from decomposed tissue by double-digest and magnetic beads
      methods].
AB  - OBJECTIVE: To study the effect of the double-digest and magnetic beads method for
      DNA extraction from 3 types of decomposed tissues. METHODS: DNA of cartilages,
      nails and joint capsule in 91 highly decomposed corpses which had not been
      extracted by common magnetic beads method, were prepared with the double-digest
      and magnetic beads methods, and quantified with Quantifiler kit, followed by
      amplification with Sinofiler kit or Minifiler kit. RESULTS: DNA concentration
      extracted from the 91 highly decomposed cartilages, nails and joint capsule
      samples was 0-0.225 ng/microL. Sixty-two samples whose DNA concentration were
      more than 0.020 ng/microL had obtained 9 or more STR loci successfully. The
      detection rate was 68.13%. CONCLUSION: The successful rate of STR genotyping for
      the 3 types of decomposed tissues can be significantly improved by the double
      digest and magnetic beads methods.

PMID- 22393596
TI  - [Rapid DNA identification using 6+1 STR kit and EX-Q20 electrophoresis].
AB  - OBJECTIVE: To establish a rapid STR genotyping method for individual
      identification. METHODS: Two hundred blood samples from FTA were collected. Equal
      amount of blood were collected by puncher and analyzed using two methods (6+1 STR
      kit in combination with EX-Q20 electrophoresis and Sinofiler kit in combination
      with POP4 electrophoresis). Consuming time and results of two methods were
      compared. RESULTS: 6+1 STR kit in combination with EX-Q20 electrophoresis method
      can obtain all genotyping results and be shorter time. CONCLUSION: 6+1 STR kit in
      combination with EX-Q20 electrophoresis method is used to STR genotyping with
      accurate, reliable results and this new method is potential value in mass
      personnel investigation and comparison in major criminal cases. It also can raise
      the work efficiency.

PMID- 22393597
TI  - [Research advancement of FTIR-MSP mapping and application value in forensic
      science].
AB  - Fourier transformation infrared microspectroscopy (FTIR-MSP) mapping technique
      can collect the infrared information from micro-samples and scan the tissue
      slides and cells. The infrared spectral information of pixels from the collected
      regions is recorded and infrared spectral maps are constructed by computer
      software. The 2D and 3D mapping images are reflected based on the distributions
      of absorbance bands. The biochemical compositions, molecular distribution,
      metabolic changes of tissues and cells are analyzed by the technique due to
      infrared spectroscopy being sensitive to biomolecules. The article reviews the
      recent research of FTIR-MSP mapping and explores the future potential value in
      forensic science practice.

PMID- 22393598
TI  - [Applications of DNA identification technology in protection of wild animals].
AB  - With the development of biotechnology, forensic DNA identification technology in
      protection of wild animals has been used more and more widely. This review
      introduces the global status of wildlife crime and the relevant protection to
      wildlife, outlines the practical applications of forensic DNA identification
      technology with regard to species identification, determination of geographic
      origin, individual identification and paternity identification. It focus on the
      techniques commonly used in DNA typing and their merits and demerits, as well as
      the problems and prospects of forensic DNA technology for wildlife conservation.

PMID- 22393599
TI  - [Application and progress of RNA in forensic science].
AB  - With the development of molecular biology, the evidences of genetics has been
      used widely in forensic sciences. DNA technology has played an important role in
      individual identification and paternity testing, RNA technology is showing more
      and more wide application in prospect. This article reviews the application and
      progress of RNA in forensic science including estimation of postmortem interval,
      bloodstain age, wound age, as well as determination of cause of death and the
      source of body fluids.

PMID- 22393600
TI  - Health plans, PBMs expand focus as they begin clinical management.

PMID- 22393601
TI  - Narrow networks found to yield substantial savings.

PMID- 22393602
TI  - Targeted medications. New focus on companion tests.

PMID- 22393603
TI  - A conversation with Paul H. Keckley, PhD. Clinical perspective critical to health
      care reform. Interviewed by John Marcille.

PMID- 22393604
TI  - 'B' isn't always for biologics.

PMID- 22393605
TI  - Engaged consumers' decisions help Aetna's CDHP program save.

PMID- 22393606
TI  - Using virtual assistant technology to improve outcomes, adherence.

PMID- 22393607
TI  - Rethinking the war on cancer.

PMID- 22393608
TI  - Dr Mehmet Oz: the crown prince of medical media on leadership.

PMID- 22393609
TI  - [Medecine Tropicale: the new begin].

PMID- 22393610
TI  - [Providing vulnerable populations in subSaharan Africa access to obstetrical
      care: strategy for improving prenatal services].
AB  - The outlook for reaching key Millennium Development goals in Africa in 2015 is
      mostly positive. However, two critical indicators, i.e., maternal and neonatal
      mortality, show lagging progress. The purpose of this report is to underline the
      importance of prenatal care in efforts to reduce maternal mortality. It describes
      the minimum prenatal care package recommended by WHO and propses strategies for
      increasing access to prenatal examination. Health education, improvement of care
      quality and outreach services are promising avenues to increasing the use of
      prenatal services.

PMID- 22393611
TI  - [Negative pressure therapy in austere environments: extremities].
AB  - Negative pressure therapy (NPT) is widely used in developed countries where it a
      technique of choice in the management of wound healing on extremities. Because of
      the cost, the specific ressources necessary forNPT are scarce in austere
      environments. This report describes a simple, economical alternative technique
      using a "breathing bandage" that can be made from from widely used surgical
      products.

PMID- 22393612
TI  - [Lithopedion formation leading to acute intestinal obstruction after 6 years:
      case report from Madagascar].

PMID- 22393613
TI  - [Pseudotumoral appearance of hepatic amebiasis].

PMID- 22393614
TI  - [2nd International Symposium on Sickle Cell Disease in Central Africa].

PMID- 22393615
TI  - [FAV-Africa: a polyvalent antivenom serum used in Africa and Europe].
AB  - FAV-Afrique is a polyvalent snake antivenom, elaborated by immunisation of horses
      with venom from 10 different snake species among the most dangerous in Africa and
      belonging to Elapidae and Viperidea families. Only F(ab')2 fragments are kept and
      purified. This serum is able to decrease the quantity of circulating venom and
      therefore its toxicity. Its use is indicated as soon as the first signs of
      poisoning are observed (local oedema). Twenty millimetres are administrated via
      intra-venous route whatever the weight of the patient. Re-administration may be
      performed if improvement is not sufficient. Treatment should be initiated as soon
      as possible but can be realized as long as the symptoms are present. Side effects
      (allergy) should be considered but balanced with the seriousness of poisoning.
      There is no absolute contraindication or drug interaction reported with FAV
      Africa. It is authorized and distributed in several African countries and has a
      temporary regulatory approval in France. The major limits to its use are high
      cost and storage conditions (maximum 36 months between +2 degrees C and +8
      degrees C). In the future, the new serum Antivipmyn Africa, available as a freeze
      dried product, which can be preserved at room temperature, should improve storage
      conditions and availability of treatment, especially in rural Africa.

PMID- 22393616
TI  - [An update on Lassa virus].
AB  - Lassa virus, the etiologic agent of Lassa hemorrhagic fever, infects 100,000 to
      300,000 people every year in West Africa with an overall mortality rate ranging
      from 1 to 2%. It was discovered in 1969 and remains a significant public health
      risk in endemic areas. Because airborne transmission is possible and mortality
      can be high under certain conditions, Lassa virus has been classified as a
      category A bioterrorism agent. Early diagnosis is difficult due to insidious non
      specific onset and to the great genetic divergence of the virus that makes RT-PCR
      assays unreliable. The lack of proper diagnostic tools promotes nosocomial
      infection and diminishes the efficacy of treatment. Recently, numerous advances
      have been made in the development of both diagnostic and vaccination techniques.
      The purpose of this review is to present an update on that research as well as
      the current epidemiology of Lassa virus.

PMID- 22393617
TI  - [Ronald Ross, "doctor in spite of himself" and... Nobel Laureate in medicine].
AB  - After becoming a military doctor at the behest of his father, Ronald Ross was
      destined to make a discovery of paramout importance, i.e., malaria transmission
      through mosquito bites. This landmark discovery that was the fruit of a
      combination of curiosity, tenacity and luck, earned him the Nobel Prize in
      Medicine.

PMID- 22393618
TI  - [The rehabilitation cares at the lepers].
AB  - Leprosy elimination (<1/100 000) is almost reached all around the world,
      although, but disabled people are still a lot, and they need rehabilitation as
      soon as possible. The different lesions (neurological, dermatologic and joint)
      must be treated in order to protect from handicap. Physical rehabilitation
      medicine can help with a global and polyvalent coverage. Therapeutic education
      and reinsertion are an important part.

PMID- 22393619
TI  - [Rehabilitation of war disabled people in the tropics: example from Colombia].
AB  - The purpose of this report is to describe collaboration between the health
      services of the Colombian and French armed forces. Colombia is a democratic
      country that has been undergoing a long period of insurrection resulting in a
      significant number of deaths and injuries. Permanent functional disabilities have
      taken high toll at both the individual and community level. Due to the use of
      landmines, civilians pay a heavier price than military personnel. In Columbia, a
      country of eternal snows and rain forests, disabilities are often compounded by
      concurrent diseases such as malaria or leishmaniasis. Otherwise, rehabilitation
      of soldiers wounded during a combat is fundamentally the same in tropical zones
      and Europe. Management of wounded servicemen takes place in teaching hospital
      where therapy is carried out at the same time as training in mine clearance.
      Reinsertion begins with job apprenticeship in conjunction with psychological
      support and prosthetic training. Current focus is on developing disability rights
      legislation modeled on the 2005 French law.

PMID- 22393620
TI  - [Problems of rehabilitation in patients with sickle cell disease in Cotonou,
      Benin].
AB  - BACKGROUND: Manifestations of sickle cell disease (SCD) are polymorphous from
      childhood to adulthood. OBJECTIVE: The purpose of this study was to assess
      outcomes of rehabilitation in the patients with SCD. METHOD: This retrospective
      analytical descriptive study included 160 SCD patients rehabilitated from 1998 to
      2006 at the National University Hospital in Cotonou, Benin. RESULTS: Mean patient
      was 31 years (range, 3 to 73 years). There was a female predominance (62.5%) with
      a sex ratio of 0.6. The type of SCD was HbAS in 53.1% of patients, HbSS in 21.3%,
      HbSC in 16.9%, and HbAC in 8.1%. The main clinical manifestations were classified
      as ischemic/infectious in 40% of patients, rheumatologic in 40%, and neurologic
      in 10%. Ischemic manifestations were observed in all patients with HbSS, HbSC,
      and HbAS while manifestations were preferentially neurological in patients with
      HbSS (p = 4,43.10(-3)) and rheumatologic in patients with HbAS (p<10(-3)). At the
      end of rehabilitation, persistent deficiencies, disabilities and limitations
      involved pain in 43.8% of patients, articular stiffness in 43.8%, muscular
      weakness in 46.9%, gait anomalies in 33.1%, amyotrophy in 21.2%, shortening of
      lower extremity in 16.9%, and tilting of the pelvis in 6.3%. CONCLUSION: This
      study shows that SCD is a highly debilitating disease. Although rheumatologic
      manifestations are not specific to SCD, the other complications described
      including femoral head necrosis, osteomyelitis, and stroke have been extensively
      documented in the literature. If primary prevention is unfeasible, early
      multidisciplinary management appears to be the most effective approach to
      reducing SCD-related disability.

PMID- 22393621
TI  - [Functional outcome of tuberculous arthiritis of the knee in a male Moroccan
      patient].
AB  - PURPOSE: The purpose of this article is to present a case of tuberculous
      arthritis of the knee and discuss the importance of early diagnosis and
      rehabilitatin in management outcome. CASE REPORT: A 57-year-old Moroccan man with
      no medical history presented with a mass in the left knee associated with pain
      and fever. Analysis of aspirated fluid demonstrated sterile inflammatory liquid.
      Presumptive antibiotic therapy was ineffective. Diagnosis of tuberculous
      arthritis was made based on positive tuberculin skin test and interferon-release
      assays. Diagnosis was confirmed by arthroscopic biopsy. Physiotherapy allowed
      improvement in both function and analytical test findings. DISCUSSION:
      Tuberculous arthritis is rare occurring in only 2 to 5% of people with
      tuberculosis. It can be very destructive. Diagnosis is often delayed leading to
      joint pain, tissue damage, and functional disability (e.g. inability to walk).
      Since prompt treatment (antibiotics then physiotherapy) can limit complications,
      early diagnosis is necessary and often requires deep biopsy, except endemic
      zones. In the acute phase, immobilization of the extremity in a functional
      position is necessary. When inflammatory signs subside, physiotherapy can be
      undertaken in short but frequent sessions without excessive weight or resistance.
      CONCLUSION: The functional outcome of tuberculous arthritis depends on early
      multidisciplinary care involving the rheumatologist, infectious disease
      specialist, orthopedic surgeon and attending physician.

PMID- 22393623
TI  - [Urinary disorders associated with bilharziasis. Urodynamic evaluation. Findings
      in 10 cases].
AB  - Bilharziasis urinary disorders are characterized by recurent hematuria,
      overactive bladder symptoms (urgency, frequency and urge incontinence) and
      sometimes weak stream with or without urinary retention. We report 10 cases of
      urodynamic assessment. RESULTS: The main urodynamic symptom was overactive
      detrusor with uninhibited detrusor contraction during the filling phase. Only 1
      patient had underactive detrusor leading to urinary retention. Urinary symptoms
      were secondary to a neurogenic abnormality (spinal lesion) in 2 cases, and to a
      specific lesion of bladder mucosa in 8 cases. CONCLUSION: Urodynamic
      investigations are usefull in bilharziasis urinary disorders in order to specify
      the pathophysiology of urinary symptoms and to point a specific neurogenic
      (spinal) alteration in the genesis of the urinary symptoms.

PMID- 22393622
TI  - [Amputation in low-income countries: particularities in epidmiological features
      and management practices].
AB  - The epidemiological features and management practices associated with amputation
      in low-income countries, generally synonymous with the tropics, are different
      from those observed in Western countries. Unlike developed countries, amputation
      most frequently involves traumatic injury in young active people. However,
      Westernization of the lifestyle is leading to an increasing number of cases
      involving diabetes and atherosclerotic disease. In the developing world, leprosy
      and Buruli ulcer are still significant etiologic factors for amputation. In war
      torn countries, use of antipersonnel landmines is another major cause of
      amputation with characteristic features. Management of amputees in the developing
      world is hindered by the lack of facilities for rehabilitation and prosthetic
      fitting. Many international organizations are supporting national programs to
      develop such facilities. In addition to being affordable, prosthetics and
      orthotics must be adapted to the living conditions of a mostly rural amputee
      population, i.e., heat, humidity, and farm work. The rehabilitation process must
      be part of a global handicap policy aimed at changing attitudes about disability
      and reintegrating amputees both socially and professionally.

PMID- 22393624
TI  - [Bio-ecological characteristics of Anopheles gambiae s.s. in irrigated rice
      fields of central Cote d'Ivoire].
AB  - This longitudinal entomological survey was conducted between September 2008 and
      September 2009 in the villages of Abokro and Yaokoffikro located in an irrigated
      rice farming area of central Cote d'Ivoire. The purpose was to investigate the
      bio-ecological characteristics of Anopheles gambiae s.s. during the gonotrophic
      cycle. In both villages, adult mosquitoes were captured in 72 light traps,
      collected on humans subjects at a rate of 72 man-night from 6 p.m. to 6 a.m., and
      knocked down using pyrethroid spray inside 60 sentinel houses in the early
      morning. A total of 10,312 adult mosquitoes were collected in Abokro and 7,662 in
      Yaokoffikro. Anopheles was the dominant genus at both locations. Light traps were
      three times more efficient in Abokro than in Yaokoffikro. In both places, An.
      gambiae s.s. biting rates increased gradually up to a peak observed between
      midnight and 1 a.m. In Abokro, most An. gambiae s.s. were collected inside
      sleeping rooms. The endophagic rate and indoor resting density was 67.4% (n =
      4798) and 14.9 females per bedroom per night, respectively, in Abokro as compared
      to 49.3% (n = 6775) and 2.9 females per bedroom per day, respectively, in
      Yaokoffikro.

PMID- 22393625
TI  - [Nutritional status and dietary diversity in nomadic and sedentary rural women on
      the southeast bank of Lake Chad].
AB  - Malnutrition and undernourishment are widespread in the Sahelian region of
      Africa. The purpose of this study was to assess nutritional status and associated
      risk factors among nomadic and sedentary rural women on the southeast bank of
      Lake Chad. It was a repeated cross-sectional study based on semi-structured
      interviews and anthropometric measurements. A total of 734 women including 398
      nomads and 336 sedentaries were randomly selected. Only non-pregnant women were
      included for calculation of the body mass index. Results showed a higher
      prevalence of malnutrition among nomadic women than sedentary women during the
      dry season: 48% (95% CI: 42-53) versus 16.2% (95% CI: 12-20). Obesity was
      observed in 4% (95% CI: 2.4-7) of sedentary women versus 0% of nomadic women.
      These rates were similar during the wet season. Malnutrition rates differed
      significantly (p<0.01) between the two groups within each season but not between
      seasons within each group. The average household dietary diversity score (HDDS)
      determined on a scale of 12 was low in both nomadic and sedentary women: 4.5 (95%
      CI: 4.4-4.6) and 5.1 (95% CI: 5.0-5.3) respectively. Malnutrition was
      significantly correlated with HDDS, number of children and ethnic group.

PMID- 22393626
TI  - [Adult-onset Still's disease: case report in Dakar, Senegal].
AB  - Adult-onset Still's disease is a uncommon form of inflammatory rheumatism. It has
      rarely been reported in black Africa. The purpose of this report is to describe a
      case in a 49-year-old woman from Dakar, Senegal.

PMID- 22393627
TI  - [Neuromeningeal cryptococcosis in Mali].
AB  - Cryptococcal meningitis is the most common fatal central nervous system infection
      in AIDS patients in Sub-Saharan Africa. The purpose of this prospective study
      conducted from March 2003 to February 2004 in the internal medicine and
      infectious diseases departments of the Point G University Hospital Center was to
      investigate the clinical, prognostic and epidemiological profile of Cryptococcus
      neoformans infection in patients hospitalized for brain and meningeale infection
      (BMI). Diagnosis of neuromeningeal cryptococcosis (NMC) was based on positive
      identification of Cryptococcus by direct exam of the cebrospinal fluid (CSF)
      after India ink staining and/or culture on Sabouraud medium without actidione.
      During the study period, a total of 569 patients were hospitalized including 235
      (41.3%) with HIV infection. Overall C. neoformans was identified in 14 patients.
      Median patient age was 39 +/- 8 years. There was a male preponderance with a sex
      ratio of 1.8 (9 men/5 women). Patients with BMI were HIV-positive in 85.7% of
      cases (n=12) and HIV-negative in 14.3% (n=2). The overall and HIV-specific
      prevalence of BMI was 2.5% and 5.1% respectively. The CD4 lymphocyte count was
      between I and 49 cells/mm3 in 64.3% of cases. The main clinical symptoms were
      cephalea in 85.7% of cases, altered consciousness in 50% and nausea/vomiting in
      35.7%. Neurological manifestations (hemiparesis and cranial nerve deficit) were
      noted in 14.3%. HIV infection is the main purveyor of NMC in Mali. The actual
      incidence of cryptococcosis is unclear due to the poor sensitivity of diagnostic
      techniques. This study highlights diagnostic difficulties related to clinical
      polymorphism and poor technical facilities. Agglutination testing of blood and
      CSF is recommended, but mortality remains.

PMID- 22393628
TI  - [Transmission dynamics and cost-effectiveness of rabies control in dogs and
      humans in an African city].
AB  - Control of human rabies in developing countries depends on prevention in dogs.
      The purpose of this study was to evaluate the cost-saving potential for the
      public health sector of intervention to control rabies in animal-host reservoirs.
      An existing deterministic model was adapted to allow study of dog-to-human rabies
      transmission. Model parameters were fitted to data from routine weekly reports on
      the number of rabid dogs and human rabies exposures in N'Djamena, Chad. At the
      onset of study, the estimated effective reproductive ratio (Re) was 1.01
      indicating stable low-level endemic rabies transmission. Simulations were
      performed to determine what effects mass vaccination and culling of dogs would
      have on the incidence of human rabies. Findings showed that a mass campaign
      allowing single parenteral vaccination of at least 70% of the canine population
      would be sufficient to interrupt transmission of rabies to humans for at least 6
      years. The cost-effectiveness of mass dog vaccination was compared to that of
      "postexposure prophylaxis" (PEP) which would not reduce future human exposure.
      Results showed that a sustained 5-year PEP program together with a dog
      vaccination campaign would be as cost-effective as PEP alone. Beyond a time-frame
      of 7 years, combining parenteral dog vaccination campaigns with human PEP
      appeared to be more cost-effective than human PEP alone.

PMID- 22393629
TI  - [Epidemiological and diagnostic featurers of colorectal cancer in Libreville,
      Gabon].
AB  - OBJECTIVE: The purpose of this study was to determine the epidemiological profile
      of colorectal cancer in Gabon and to describe its clinical and laboratory
      features. MATERIAL AND METHODS: This retrospective monocentric descriptive study
      was based on all cases of colorectal cancers managed at the Libreville Hospital
      Center during the 10-year period from September 1996 to September 2006. Study
      endpoints included epidemiological characteristics, anatomoclinical forms and
      diagnostic methods. RESULTS: A total of 51 cases were included. Mean patient age
      at time of diagnosis was 48 years. The sex ratio was 1.3 with a female
      predominance. Mean duration of symptoms ranged from 6 months to 1 year. Abdominal
      pain and digestive disturbances were the most common manifestations. Lower
      digestive-tract endoscopy was performed in 49 patients. The tumor was located at
      rectosigmoid junction in 80% of cases. Lieberkuhnian adenocarcinoma accounted for
      98% of cases. CONCLUSION: Initially described in industrialized countries,
      colorectal cancer is now being reported in developing regions, even though data
      from the literature and Gabonese cancers register (1984-93) indicate otherwise.
      It often involves young adults. The rectum was the most frequent site in this
      study. Delayed diagnosis is the main reason for poor prognosis. Education to
      improve awareness of early clinical signs as well improvement of diagnostic
      facilities should allow early detection and better prognosis of colorectal cancer
      in Africa.

PMID- 22393630
TI  - [Knowledge, attitudes and practices of healthcare providers in Togo regarding
      prevention of mother-to-child transmission of HIV in 2010].
AB  - OBJECTIVE: To evaluate the knowledge, attitudes and practices of health care
      providers (HCP) in Togo regarding prevention of mother-to-child transmission of
      HIV (PMTCT). METHOD: A cross-sectional study was conducted in 22 antenatal
      clinics with PMTCT programs from January 18 to February 6, 2010. Clinic selection
      was based on attendance and local factors. Data were collected through interviews
      conducted by 23 trained investigators. RESULTS: A total of 97 HCP were
      interviewed at the 27 selected clinics. Most, i.e., 76%, had received PMTCT
      training. In terms of knowledge, interview data revealed the following strengths:
      83% of HCP identified transmission from mother to child as the main route of HIV
      transmission in children < 15 years; 87% asserted that HIV-infected pregnant
      women do not always transmit HIV to their children; 77% knew that the ELISA test
      was performed after 18 months: and 96% had a clear notion about feeding infants
      born to HIV-infected mothers. Knowledge assessment revealed the following
      weaknesses: 30% of HCP had never heard of polymerase chain reaction; 27% said
      that confidentiality about HIV status was not always necessary; and 22% were
      unaware that decontamination of equipment using a chlorine solution kills HIV. In
      addition, interview data revealed the following positive attitudes and practices:
      83% of HCP were willing to continue working in a center with a PMTCT program and
      87% referred women pregnant for the HIV serology. On the negative side, however,
      only 27% of HCP summonsed husbands whose wives tested positive for HIV.
      CONCLUSION: This investigation shows that the knowledge, attitudes and practices
      of HCP in Togo regarding PMTCT is fairly good. However, it also revealed several
      weaknesses that should be addressed by further training.

PMID- 22393631
TI  - [Nocardiosis: 4 cases in Senegal].
AB  - The purpose of this report is to describe four cases of nocardiosis observed over
      an eight-year period in medical units of Principal Hospital in Dakar, Senegal. It
      is a rare infection occurring mainly in people with weakened immune systems.
      Pulmonary forms are predominate and clinical and laboratory presentation can
      mimic pulmonary tuberculosis. Diagnosis should be suspected in patients
      presenting pulmonary infections and negative sputum bacilloscopy. Nocardia
      bacteria should be identified before starting antibiotic treatment. Patients
      require long-term antibiotic treatment with third generation cephalosporins or
      sulfamethoxazole-trimethoprim.

PMID- 22393632
TI  - [Fatal miliary tuberculosis in an HIV-infected Cameroon woman: disseminated
      histoplasmosis due to Histoplasma capsulatum capsulatum].
AB  - The purpose of this report is to describe the first Cameroonian case of
      disseminated histoplasmosis due to Histoplasma capsulatum capsulatum in
      association with HIV infection. The patient was a 34-year-old HIV1 infected
      woman. Diagnosis of histoplamosis was made in post-mortem. The similarity of the
      clinical symptoms with disseminated tuberculosis makes diagnosis of mycosis
      difficult. Active and effective care of histoplasmosis is urgently necessary for
      the HIV infected persons.

PMID- 22393633
TI  - [Visceral leishmaniasis: pediatric case report observed outside the traditional
      foci in Cameroon].
AB  - The purpose of this report is to describe an autochtonous case of visceral
      leishmaniasis with cachexia, fever, splenomegaly, ascitis and severe anemia
      observed in an eight-year-old boy from a region in eastern Cameroon outside the
      traditional disease foci. Diagnosis was confirmed based on demonstration of
      Leishmania amastigotes on bone marrow smear. The patient was treated with
      meglumine antimoniate but died on the 6th day of treatment.

PMID- 22393634
TI  - [Necrotic lesion of the lip and cough with fever: cutaneous and pulmonary
      anthrax].
AB  - Anthrax disease is an anthropozoonosis caused by Bacillus anthracis. It appears
      in three clinical forms: pulmonary, intestinal, and cutaneous. We report a case
      of pulmonary and cutaneous anthrax in a one-year-old Moroccan infant.

PMID- 22393635
TI  - [Ultrasonographic features of liver abscess based on a 58-case series in
      Cameroon].
AB  - Amoebic abscess is the most frequent type of liver abscess in tropical areas,
      including in immunocompromised patients. Abscesses affect the right lobe in 74%
      of cases and are solitary in more than 80%. The ultrasonographic features of
      liver abscess vary according to stage, viscosity of liquid contents, amount of
      debris inside and presence of gas bubbles. Multiple small abcesses are mainly
      associated with pyogenic abscess and are promoted by HIV infection.

PMID- 22393636
TI  - [Peritoneal tuberculosis and HIV infection in adults: 32 cases in Lome (Togo)].
AB  - The purpose of this prospective study is to describe a series of adult HIV
      infected patients treated for peritoneal tuberculosis over a 36-month period in
      Lome, Togo. A total of 32 cases were included. Mean patient age was 38 years
      (range, 20 to 69). The M/F sex ratio was 0.52. Ascites with fever was observed in
      all cases. Ascitic fluid was exsudative in 10.6% of cases and lymphocytic in
      93.7%. Peritoneal tuberculosis was isolated in 27 patients, associated with
      pleural involvement in 15.6 % of cases, hematological in 75% and hepatic in
      21.9%. Patients responded poorly to therapy and prognosis was unfavorable with a
      mortality rate of 12.5%. HIV infection substantially alters the epidemiological,
      clinical and therapeutic profile of peritoneal tuberculosis.

PMID- 22393637
TI  - [Metabolic disorders and cardiovascular risk factors observed in patients
      infected by the HIV with antiretroviral therapy in Burkina Faso].
AB  - The purpose of this descriptive transverse study is to describe metabolic
      disorders and cardiovascular risk factors in HIV-infected patients undergoing
      antiretroviral therapy in the day-care unit of the University Hospital of
      Ouagadougou, Burkina-Faso. A total of 100 patients (Burkinavi cohort) undergoing
      antiretroviral therapy with a minimum of 42-months of follow-up (October 2005 to
      Mars 2009) were included. There were 77 females and 33 males with a mean age of
      37 years. Most patients, i.e., 95%, were positive for HIV1. Mean body mass index
      was 22 kg/m2. Mean CD4 count was 280/mm3. Viral load was undetectable in 66 of
      the 71 patients who underwent viral load testing. Retroviral therapy consisted of
      the TriomuneR combination (Stavudine + lamivudine + nevirapine) at a fixed dose
      in 27 cases. Cardiovascular risk factors included family history of high arterial
      blood pressure in 5 patients, smoking in 4, and obesity in 8. During follow-up,
      seven patients presented hypertension. Metabolic disorders included hyperglycemia
      (4%), hypertriglyceridemia (17%) and hypercholesterolemia (14%). Lipodystrophia
      was noted for 6 patients. Despite the short follow-up period, metabolic disorders
      and cardiovascular risk factors were observed at our patients under
      antiretroviral therapy.

PMID- 22393638
TI  - [Intrapartum obstetrical transfers: sociodemographic, clinical and prognosistic
      aspects in Conakry, Guinea].
AB  - The objectives of this descriptive prospective study were to determine the
      frequency of intrapartum obstetrical transfers, assess the sociodemographic
      profile of parturients requiring transfer, describe transfer modalities, and
      assess maternal and newborn outcomes. Study included all patients requiring
      intrepartum obstetrical transfer to the Ignace Deen University Hospital
      Gynecology Obstetrics Clinic in Conakry, Guinea from August 1st, 2009 to July
      31st, 2010. Out of 3122 deliveries during the study period, intrapartum transfer
      was required in 220 cases, i.e. 7.05%. Mean patient age was 23.2 years (range, 14
      to 44). The risk for intrapartum transfer was higher among multiparous or
      nulliparous women (incidence, 8.79%) and adolescents (incidence, 10%). Patients
      requiring transfer were mainly housewives (60%) and uneducated women (57.27%).
      Most had had an insufficient number (<4) of antenatal examinations (76.36%) and
      had been examined at peripheral maternity units (62.73%). In 175 cases (79.54%),
      patients were transferred by taxi. In 191 patients, treatment required surgery
      including 130 caesarian sections. There were 12 maternal deaths (5.45%) and 45
      neonatal deaths out of 242 newborns including 22 twin deliveries (18.59%).
      Further work is necessary to improve referral and transfer at all levels of the
      health pyramid.

PMID- 22393639
TI  - [Childhood acute lymphoblastic leukemia: 12 cases in Mali].
AB  - INTRODUCTION: Data about childhood acute lymphoblastic leukemia, the most common
      childhood malignancy in industrialized countries, are scarce in African
      publications. The purpose of this prospective, unicentric study were to assess
      the socio-demographic, clinic and laboratory characteristics of the children
      treated for lymphoblastic leukemia in our pediatric oncology unit in Gabriel
      Toure Teaching Hospital in Bamako, Mali. PATIENTS AND METHODS: This study
      includes all children between 1 and 15 years old treated for cytologically
      documented acute lymphoblastic leukemia from January 1, 2007 to September 30,
      2009. RESULTS: A total of 12 cases including 8 boys and 4 girls (sex ration, 2)
      were treated during the study period. Mean age was 92 months. Age was less than 4
      years old in 2 cases. 5 (41,7%) were between 5 and 9 years in 5 (41.7%) and
      between 10 to 15 years in five. At the time of presentation, 9 patients (75%)
      were in a cachectic state; 10 had lymphadenopathies, splenomegaly and
      hepatomegaly; and 2 had neurological involvement. The delay for definitive
      diagnosis was 5 months in 4 cases (33,3 %) and less than 5 months in the
      remaining cases. Initial white blood cell count was more than 50 000/mm3 in 10
      cases and less less than 50 000/mm3 in 2 cases. All patients were treated using
      the LAL GFAOP protocol including LAL1 in 6 cases, LAL2 in 5 and LAL3 in 1.
      Treatment complications were included 6 undocumented infections in 6 cases,
      hemorrhage in 2 and severe anemia in 4. Four patients died. At 5 years follow-up,
      overall survival rate was 66,7%. CONCLUSION: A multicentric study including a
      greater number of children is needed to increase understanding of the
      characteristics of childhood acute lymphoblastic leukemia in sub-Saharan Africa.

PMID- 22393640
TI  - [Pneumocystis jiroveci pneumonia: first documented case in Libreville, Gabon].
AB  - The purpose of this report is to describle the first documented case of
      pneumocystosis in Gabon. Diagnosis was confirmed based on microbiological methods
      in a 59-year-old immunodepressed HIV-positive man. Diagnosis was further
      documented by observation of Pneumocystis jiroveci cysts in the broncho-alveolar
      lavage (BAL) after Gomori-Grocott color reaction. The patient responded well to
      treatment with Cotrimoxazole, corticoids and oxygen.

PMID- 22393641
TI  - [Seroprevalence of HBsAgs in patients with rheumatoid arthiritis in a hospital
      setting in Senegal].
AB  - PURPOSE: Rheumatoid arthritis is the most common chronic inflammatory joint
      disease in adults. In Senegal, where biotherapy is unavailable, treatment of RA
      relies on a combination of glucocorticoids and disease-modifying antirheumatic
      drugs (DMARD). Since DMARD, particularly methotrexate, induce hepatotoxicity
      pretreatment assays of serum transaminase and albumin levels, as well as
      serological tests for the hepatitis B and C viruses is recommended. Hepatitis B
      virus (HBV) infection is endemic in Africa, particularly in Senegal. The purpose
      of this study was to assess the seroprevalence of the HBV surface antigen (HBsAg)
      for HBV in 258 patients with RA in Senegal as a basis for defining the least
      hepatotoxic DMARD for these patients and ensuring the most suitable monitoring.
      METHOD: This retrospective study was based on a review of the medical records of
      patients examined between January 2005 and December 2009 at the rheumatology
      outpatient clinic of the Aristide Le Dantec Teaching Hospital in Dakar, Senegal.
      All patients met the American College of Rheumatology criteria for RA. RESULTS: A
      total of 258 patients were tested for HBsAg. Tests were positive in 6 for a
      seroprevalence of 2.3%. All 6 positive patients were women with a mean age of
      48.7 years (range, 16-79 years). Transaminase levels were normal in 5 patients.
      In the remaining patient, ASAT level elevation were twice normal and ALAT was
      normal. No patients had clinical evidence of liver disease. CONCLUSION: HBsAg
      seroprevalence in our population of patients with RA was lower than in the
      general population of Senegal: 2.3% versus 15%-18%. No evidence indicated that
      HBVinfection produced specific features in patients with RA. Based on these
      findings, widespread use of methotrexate in optimal dosages appears safe in
      patients with RA in Senegal. Treatment should be accompanied by careful attention
      to HBV prevention.

PMID- 22393642
TI  - [Major salmonellosis in Benin].
AB  - Although salmonellosis is a common endemo-epidemic disease in Benin, there is a
      paucity of data about it. The purpose of this cross-sectional study was to
      determine the incidence of major salmonellosis requiring hospitalizaton and to
      describe its epidemiological, clinical, and serologic features as well as
      treatment and outcome. Consecutive cases observed at the Medical Department of
      Parakou University Hospital in Benin between January 1, 2005 and December 31 2007
      were included. Salmonellosis was defined on the basis of clinical and serological
      criteria. Among the 2,520 patients hospitalized during the study period,
      salmonellosis was diagnosed in 135 (5.4% [95% CI 4.5%-6.3%]). Highest incidences
      were observed in January, July, October and November. The main symptoms were
      headache, fever, fatigue and abdominal pain. The Salmonella typhi serotype was
      identified in 94.8% of patients. Two patients presented co-infection, i.e.,
      Salmonella typhi with paratyphi A in one case and Salmonella typhi with paratyphi
      B in the other. Fluoroquinolones were used for treatment in 79.3% of patients.
      Outcome was favorable in 62.2%. The main complications were,typhoid digestive
      perforation in 11.1%, and gastrointestinal bleeding in 8.1%. The mortality rate
      was 4.4% (n=6). These data are consistent with previous reports in the literature
      and confirm the frequency and severity of salmonellosis in Benin.

PMID- 22393644
TI  - [Management of high-grade atrioventricular block in Lome, Togo].
AB  - The purpose of this cross-sectional study was to describe epidemiological,
      clinical and therapeutic aspects of high-grade atrioventricular block in Lome.
      Out of 2245 patients hospitalized between June 2004 and May 2009, a total of 22
      cases of high-grade atrioventricular block were detected thus a prevalence of 1%.
      The main symptoms were syncope and presyncope (73%) and dyspnea (50%). There was
      77.2% of chronic grade III atrioventricular block and 22.8% of grade II
      atrioventricular block. A pacemaker has been established in 8 patients (40% of
      the patients presenting a class I indication) in VVI (R) mode. We noted 59% of
      deaths among patients who did not benefited from any cardiac pacing.

PMID- 22393643
TI  - [Hysterectomy: indications and advantages of the vaginal route in Mali].
AB  - The purpose of this report was to determine the frequency of hysterectomy and
      describe its indications and outcomes. A retrospective, descriptive study related
      to active hysterectomy of was conducted at the reference health centre of commune
      V in Bamako, Mali from January 1st, 2004 to December 31st, 2008. All hysterectomy
      patients with complete medical files were included. A total of 172 files were
      identified including 152 that were complete. Hysterectomy accounted for 1.38% of
      all interventions during the study period. The procedure was carried out in
      emergency in 0.14% and electively in 13.39%. Mean patient age was 47.9 +/- 11.7
      years; 89 patients were older than 45 years. The indications for hysterectomy
      were complicated uterine fibroids in 82 patients, genital prolapse in 44,
      adenomyosis in 10, obstetrical hysterectomy in 13 and cervical dysplasia in 3.
      The abdominal route was used in 100 patients (65.8%) and the vaginal rout in 52
      (34.2%). The duration of the procedure and hospital stay was longer after
      hysterectomy by the abdominal (p<0.05). Perioperative complications were observed
      in 17% of patients after abdominal hysterectomy versus 7.69% after vaginal
      hysterectomy. Two maternal deaths due to hemorrhagic shock were observed after
      obstetrical hysterectomy. Hysterectomy is a frequent intervention that is not
      without complication risks. Choice of route depends on the indication and skill
      of the operator. Although endoscopic surgery is still difficult to perform in
      developing countries, development of vaginal hysterectomy is necessary to reduce
      perioperative complications.

PMID- 22393646
TI  - Rick Santorum's inconvenient truths: the former Senator puts the hard questions
      on the table, even at his peril.

PMID- 22393647
TI  - Getting to no: the science of building willpower.

PMID- 22393645
TI  - [Cardiac stimulation in Africa: necessity must overcome doubt].

PMID- 22393648
TI  - [It is better to prevent than cure].

PMID- 22393649
TI  - [Vascular rehabilitation of patients suffering from peripheral arterial disease].
AB  - Rehabilitation programs represent an important and valuable tool for patients
      suffering various diseases. Supervised exercise programs for patients with
      peripheral arterial diseases have been shown to be efficacious in ameliorating
      walking performances and quality of life of such patients. With this regards the
      angiology service of the CHUV in Lausanne has established a multidisciplinary
      supervised program of vascular rehabilitation. This article describes
      organisation and characteristics of such a program.

PMID- 22393650
TI  - [Prevention of chronic venous disease: which advice for our patients?].
AB  - Chronic venous disease (CVD) is a major public health problem due to its high
      prevalence and socioeconomic costs. In absence of adequate care, it can lead to
      chronic venous insufficiency (CVI). Disturbed venous-flow patterns lead to venous
      hypertension. Therefore, prevention of CVD involves venous hypertension
      reduction. In primary prevention, it is essential to inform the patient about
      necessary lifestyle changes. In case of CVD, it is essential to propose treatment
      (compression, venoactive drugs, and interventional treatments) to avoid CVI
      appearance and eventually offer the best therapy solutions for CVI complications.

PMID- 22393651
TI  - [Prevention of post-thrombotic syndrome].
AB  - Post-thrombotic syndrome (PTS) is the most frequent chronic complication of deep
      vein thrombosis (DVT) with an estimated prevalence of 30-50%. PTS is a
      significant cause of disability, especially when complicated by venous ulcers.
      Therefore, PTS has important socio-economic consequences for both the patient and
      the health care system. Actually, the efficacy of PTS treatment is very limited;
      therefore, best treatment remains prevention. Compression therapy, particularly
      by graduated compression stockings (GCS) has a pivotal role in PTS prophylaxis.
      Aim of this article is to resume state of the art literature on this subject.
      Recommendations on PTS prevention have even been reported.

PMID- 22393652
TI  - [Lymphatic disorders and prevention of their complications].
AB  - The prevalence of lymphedema is clearly underestimated. Too few patients receive
      treatment. It requires several specifically trained participants and must be
      conceived in the long term given the chronic nature and the incurability of this
      pathology. Prevention is therefore of major importance. Successfully applied to
      operated women for breast cancer, other models of coverage deserve to be
      developed to reduce the incidence of lymphedema and its complications,
      particularly after oncologic, orthopedic and vascular surgery and for patients
      affected by venous insufficiency.

PMID- 22393653
TI  - [Bleeding risk in patients with venous thromboembolism].
AB  - About 2 to 2,5% of patients with venous thromboembolism suffer from a major bleed
      in the first 90 days of treatment with anticoagulation. Many predictors of
      hemorrhages have been identified, and include the stability of INRs, a bleeding
      history, cancer, chronic kidney disease and an advanced age. This knowledge may
      help care-providers to identify high-risk situations and to determine the best
      duration of treatment for their patients. Bleeding prediction rules for prevalent
      users of warfarin have not been validated for patients in venous thromboembolism,
      and their usefulness remains to be determined.

PMID- 22393654
TI  - [Vascular follow up in patients suffering from peripheral arterial disease and
      undergoing revascularization].
AB  - The rapid evolution of revascularization techniques has allowed an improvement in
      quality of life of patients with peripheral artery disease. The angiological
      follow-up aims to insure durable results of revascularization, to diminish risk
      of amputation and to limit progression of atheroma plaques. The patient history
      and physical examination are essential in evaluating impact of peripheral artery
      disease upon quality of life and insuring the appropriate control of
      cardiovascular risk factors.

PMID- 22393655
TI  - [It is important to anticipate but acting is the priority!].

PMID- 22393656
TI  - [Measuring the quality of cardiovascular risk assessment tools].

PMID- 22393657
TI  - [The flu: surveillance and action via the web].

PMID- 22393658
TI  - [Electronic certification of death].

PMID- 22393659
TI  - [Your soul weighs about how much, do you estimate?].

PMID- 22393660
TI  - [Planetesante.ch: the Swiss health information site].

PMID- 22393661
TI  - Parental controls: past indiscretions lead to tighter reins on new and future
      conversion foundations.
AB  - Conversion foundations created when a struggling not-for-profit hospital sells to
      a for-profit company have billions at their disposal to help their communties.
      The decision to create one and its direction are locally based. "It's really the
      community that drives it," says Martin Rash, of RegionalCare.

PMID- 22393662
TI  - Public outcry thwarts deal: move to create foundation left to attorney general.

PMID- 22393664
TI  - Putting it to the test: new exam offers credentials in patient safety field.

PMID- 22393663
TI  - Transparency tussle: hospitals, devicemakers clash over price disclosure.

PMID- 22393665
TI  - Safety 'milestone': hospital compare adds central line infection data.

PMID- 22393666
TI  - Price increases ease: Medicare curbs slow some growth; Medicaid ticks up.

PMID- 22393667
TI  - The best of times? Economic woes and prices depress healthcare access in our era.

PMID- 22393668
TI  - The ACO journey: why one prominent provider is embracing the change.

PMID- 22393669
TI  - Trustees of the Year 2012. A passion for the cause.

PMID- 22393670
TI  - Trustees of the Year 2012. Leadership amid turmoil.

PMID- 22393671
TI  - Trustees of the Year 2012. Strong ties to the community.

PMID- 22393672
TI  - Trustees of the Year 2012. Backbone of the operation.

PMID- 22393673
TI  - Docs helping docs embrace IT: organization uses online tools to promote value of
      the technology.

PMID- 22393674
TI  - Lessons from prohibition.

PMID- 22393675
TI  - Passion powers success.

PMID- 22393676
TI  - Doctor on solid footing by addressing health need.

PMID- 22393677
TI  - Physician-designed app empowers patients.

PMID- 22393678
TI  - The CPT code changes you need to know.

PMID- 22393679
TI  - Doctors' lifestyle changes have ripple effect.

PMID- 22393680
TI  - EHR templates: time-saver or patient safety risk?

PMID- 22393681
TI  - The case for concierge medicine.

PMID- 22393682
TI  - Primary synovial sarcoma of the kidney. A case report with pathologic appraisal
      investigation and literature review.
AB  - Synovial sarcoma (SS) is a soft tissue neoplasm with clearly defined histologic,
      immunohistochemical and molecular features that usually arises in the extremities
      of young adults. The occurrence of these tumors in the kidney is extremely rare
      and have been prevalently described in case reports. The objectives of this work
      were to evaluate the frequency of primary renal synovial sarcomas and the
      pathologic progression in recognition of this possibly under-diagnosed entity. A
      comprehensive review of the literature has also been performed with a focus on
      survival. We report the clinico-pathological features of an intrarenal SS
      occurring in a 67-year-old man. The tumour, measuring 4 cm in its greatest
      diameter, completely replaced the cortex and the medulla of the inferior region
      of the left kidney compressing the iliopsoas muscle. Radiological imaging was
      consistent with a renal cell carcinoma. Histologically, the tumour was composed
      of atypical monotonous vimentin+, CD99+, bcl-2+ spindle cells exhibiting a
      haphazard fascicular growth pattern and a high mitotic rate (3 to 5 mitoses per
      HPF). The diagnosis was supported by reverse transcription-polymerase chain
      reaction which demonstrated SYT-SSX2 gene fusion. The patient was alive with
      local recurrence of disease 24 months after surgery. Synovial sarcomas occurring
      in the kidney, in analogy to other sites, tend to have an aggressive biologic
      behaviour. Despite being extremely uncommon, with only 44 cases reported to date,
      they should be included in the differential diagnosis of benign and malignant
      spindle cell tumours of the kidney. This study also emphasizes the importance of
      a correct pathologic diagnosis for prognostic and therapeutic implications.

PMID- 22393683
TI  - Oncocytic carcinoma of the parotid gland: case report and review of the
      literature.
AB  - OBJECTIVES: To date 70 cases of oncocytic carcinomas (OCs) have been described in
      55 reports. We describe an OC of the parotid gland in a 56-year-old man with
      simultaneous breast cancer. METHODS: In June 2006, a 56-year-old man was referred
      to the Otorhinolaryngology Division for a painless right preauricolar mass. The
      facial nerve was functionally normal. Total parotidectomy with facial nerve
      preservation was performed. In January 2007, the patient was referred to the
      Surgical Division for a left mammary nodule. Total mastectomy with axillary
      lymphoadenectomy was performed. RESULTS: The mass of the parotid gland measured
      3.5 x 3 cm. Histology showed sheets, islands and nests composed of large, round
      to polyhedral cells with fine, granular, eosinophilic cytoplasm and round
      vesicular nuclei, with prominent nucleoli. The tumour cells were positive for
      immunohistochemical staining with antimitochondria antibodies. Histological
      examination of the mammary tumour showed invasive ductal carcinoma Grade III
      (Nottingham Histologic Score) with metastasis in 12 axillary lymph nodes.
      Chemotherapy was performed. At present, the patient is free of recurrences or
      metastases. CONCLUSIONS: Histologically, there is a spectrum of malignant parotid
      gland neoplasms that have prominent eosinophilic granular cytoplasm due to
      increased number of mitochondria. OCs have cytoplasm packed with mitochondria,
      while the term "oncocytoid" should be employed for tumours that have abundant
      eosinophilic granular cytoplasm, but ultrastructurally do not possess marked
      mitochondrial hyperplasia. All reported cases of OC should be defined "oncocytic
      like carcinoma" when only haematoxylin and eosin staining is performed.

PMID- 22393685
TI  - Breast cancer and primary systemic therapy. Results of the Consensus Meeting on
      the recommendations for pathological examination and histological report of
      breast cancer specimens in the Marche Region.
AB  - Primary systemic therapy (PST) adds some practical problems to the pathologic
      examination of neoplastic breast tissue obtained from patients before and after
      chemotherapy. Pathologists, oncologists, breast surgeons, radiotherapists and
      radiologists in the Marche Region held a Consensus Meeting in Ancona on May 13,
      2010, in which 15 statements dealing with neoadjuvant chemotherapy were approved
      by all participants. The first two statements are related to the pre-PST phase
      and concern the technical procedures and the histological report of the core
      biopsy. The other statements deal with similar issues of the post-PST surgical
      specimen.

PMID- 22393687
TI  - Reactive pseudo-glandular mesothelial hyperplasia in testis tunica vaginalis: a
      case report.
AB  - A case of benign reactive pseudo-glandular mesothelial hyperplasia arising in the
      context of chronic vaginitis in presented: morphological and immunohistochemical
      investigations and differential diagnoses are described.

PMID- 22393686
TI  - Histogenetic and taxonomic considerations on a case of post-traumatic bizarre
      parosteal osteochondromatous proliferation (BPOP).
AB  - A case of bizarre parosteal osteochondromatous proliferation (BPOP) arising in
      the head of the fibula of a young man following injury on the lateral aspect of
      the knee is reported. Microscopically, four zones could be recognized proceeding
      from the periphery to the deep portion: 1) an outer thick fibrous cap showing an
      abundant cellular component, composed of thin spindled elements of fibroblastic
      appearance, haphazardly arranged and exhibiting intense and diffuse
      immunohistochemical expression of S100 protein (a previously unreported
      observation); 2) an irregular and atypical cartilaginous cap beneath the fibrous
      cap; 3) a layer of blue bone in which islands of atypical chondrocytes are still
      present but gradually decreasing, moving towards the deeper areas; 4) a layer of
      mature bone, pink bone, which is implanted in the skeletal segment (the deep
      margin is devoid of periosteum). The intratrabecular spaces of blue or pink bone
      did not contain haematopoietic marrow, but rather a loose myxoid stroma. This
      case confirms the fact that BPOP can occur in skeletal segments other than those
      indicated in the original report of Nora, and that trauma, even if minor, is an
      important factor in the development of the lesion. The latter begins at the
      periosteal level, where fibroblasts may acquire a chondroformative function
      (becoming chondrofibroblasts), as witnessed by the strong and widespread
      expression of P S100, first documented in this report.

PMID- 22393684
TI  - Epidemiological changes in breast tumours in Italy: the IMPACT study on
      mammographic screening programmes.

PMID- 22393688
TI  - Incidental finding of peripheral B-cell non-Hodgkin lymphoma, lymphocytic/CLL
      type, of the gallbladder in a patient with chronic cholecystitis.
AB  - Although lymphoma involvement of the gallbladder, especially by MALT and large
      cell types, is rare, this possibility should be considered in patients with
      symptoms of acute cholecystitis. A cholecystectomy was performed in a 79-year-old
      male patient with a clinical diagnosis of chronic cholecystitis. Histologically,
      the specimen showed an incidental finding of a small lymphocytic lymphoma (CLL)
      by morphologic and immunophenotyping studies, subsequently confirmed with flow
      cytometric analysis of blood. During follow-up, multiple lymph node enlargement
      was detected. An axillary node, excised and submitted to our department, was
      positive for lymphoma involvement. The bone marrow was negative.

PMID- 22393689
TI  - Nodular hidradenoma in a 19-year-old woman.
AB  - Hidradenomas are rare adnexal tumors. Recently, two groups have been
      individualized: those with eccrine differentiation called poroid hidradenoma and
      those with apocrine differentiation called clear-cell hidradenoma or nodular
      hidradenoma. Herein we report a case of 19-year old woman with a nodular
      hidradenoma of the scapular region. Our report highlights the clinic-pathological
      characteristics of these tumors and emphasizes the benefit of complete local
      excision to prevent risk of recurrence and possible malignant potential.

PMID- 22393690
TI  - [Evaluation of the effect of the traditional Chinese medicine tongxinluo or
      ginseng on excess fatigue rats studied by metabonomics approach based on liquid
      chromatography-mass spectrometry].
AB  - Excess fatigue is a pathological state of continuing accumulation of fatigue,
      which may cause the deterioration of body health, occurrence of diseases, and
      even lead to death. A metabonomics study was performed on the excess fatigue rats
      treated with traditional Chinese medicine Tongxinluo or ginseng based on ultra
      fast liquid chromatography coupled with ion trap-time of flight mass spectrometry
      (UFLC-IT-TOF-MS). The plasma metabolic profiling data of the control rats, excess
      fatigue rats, and excess fatigue rats treated with Tongxinluo or ginseng were
      acquired. The orthogonal partial least squares analysis (OPLS) was applied for
      the multivariate statistics and the discovery of important differential
      metabolites distinguishing the excess fatigue rats treated with Tongxinluo or
      ginseng from the control rats and excess fatigue rats. The results showed
      tryptophan, bile acid, lysophosphatidylcholine metabolism were disturbed in the
      excess fatigue rats. The metabolic pattern including the related metabolic
      pathways of the rats, being treated with Tongxinluo or ginseng, was adjusted
      towards the normal state.

PMID- 22393691
TI  - [Determination of 6 antiestrogens in fish tissues by ultra performance liquid
      chromatography-tandem mass spectrometry].
AB  - A comprehensive analytical method based on ultra performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed for the
      simultaneous determination of 6 antiestrogens (toremifene, clomiphene, tamoxifen,
      raloxifene, anastrozole and letrozole) in fish muscle and liver. The multi
      reaction monitoring mode was employed for the determination. The homogeneous fish
      tissue samples were ultrasonically extracted with acetonitrile, and then the
      supernatants were diluted by water. The target compounds were concentrated and
      purified by a mixed-mode cationic-exchanger (MCX) cartridge, and then separated
      on an ACQUITY UPLC BEH C18 column (100 mm x 2.1 mm, 1.7 microm) using a binary
      mobile phase gradient with water containing 0.1% formic acid and acetonitrile.
      The limits of quantification (LOQ, S/N = 10) of the 6 antiestrogens were 0.1 -
      0.3 microg/kg in muscle and liver samples. The average recoveries of target
      compounds (spiked at four concentration levels) based on internal standard
      calibration were in the range of 84.9% - 112.2% with the relative standard
      deviations of 0.9% - 14.3%. This method can be applied to the trace analysis of
      target drugs in fish muscle and liver samples.

PMID- 22393692
TI  - [Determination of commonly abused dyes in food by liquid chromatography-tandem
      mass spectrometry].
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed
      for the determination of commonly abused dyes in candy, sirup, liquid milk and
      fruit juice. The test sample was dissolved and diluted with water, then cleaned
      up by polyamide solid phase extraction. The LC separation was performed on an
      Agilent XDB-C18 column with 20 mmol/L ammonium acetate solution and acetonitrile
      as the mobile phase in a gradient elution mode. The dyes were determined by MS/MS
      in negative electrospray ionization mode, and quantified by matrix-matched
      external standard method. The calibration curves showed good linearity in the
      range of 0.5 - 50 mg/L with the correlation coefficients (r) greater than 0.99.
      The limits of quantitation (S/N > 10) were 0.5 mg/kg, and the limits of detection
      (S/N > 3) were 0.1 mg/kg. The recoveries of dyes in food samples at the three
      spiked levels of 0.5, 5 and 50 mg/kg were in the range of 62.6% - 115.3% with the
      relative standard deviations (RSDs) of 2.6% - 26.3%. The method can meet the
      requirements for the determination of the dyes in food samples for import and
      export inspection.

PMID- 22393693
TI  - [Rapid determination of 6 pesticide residues in tomato paste by ultra performance
      liquid chromatography-tandem mass spectrometry].
AB  - An ultra performance liquid chromatography-tandem mass spectrometric method (UPLC
      MS/MS) was established for the simultaneous determination of imidacloprid,
      carbendazim, thiophanate-methyl, propamocarb, methomyl and dimethomorph residues
      in tomato paste. The samples were extracted by methanol-water (1: 1, v/v)
      containing 0.1% (v/v) acetic acid. The separation was performed on a Waters
      Acquity UPLC system with a BEH C18 column with the gradient elution of methanol
      and water (containing 10 mmol/L ammonium acetate). The six pesticides were
      determined in the modes of electrospray positive ionization (ESI+) and multiple
      reaction monitoring (MRM). The analytes were quantified by matrix-matched
      standard solution, and the calibration curves showed good linearity within the
      concentrations of 0.005 to 0.2 mg/L and the correlation coefficients (r) were
      more than 0.995. The average recoveries of the six pesticides ranged from 66.8%
      to 102.9% in the three spiked levels of 0.02, 0.05 and 0.2 mg/kg. The relative
      standard deviations (RSDs) were all less than 15%. The limits of quantification
      (LOQ, S/N > 10) were 0.02 mg/kg for the all analytes. The results indicate that
      the method is easier, faster, more sensitive, and suitable for the qualitative
      and quantitative confirmation of the six pesticide residues from tomato paste.

PMID- 22393694
TI  - [Determination of aristolochic acids A and B in Chinese herbals and traditional
      Chinese patent medicines using ultra high performance liquid chromatography
      triple quadrupole mass spectrometry].
AB  - A method for the simultaneous determination of aristolochic acids A and B in some
      Chinese herbals and traditional Chinese patent medicines by ultra high
      performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC
      MS/MS) was developed. Fourteen samples, including Radix Bupleuri, Radix
      Glycyrrhizae, Radix Platycodonis, Longdanxieganwan, Xiaopangwan, Slimming Tea,
      etc., were extracted with methanol-water (70: 30, v/v) and purified with Oasis
      MAX solid-phase extraction cartridges, then analyzed on an Eclipse RP HD C18
      column (150 mm x 2.1 mm, 1.8 microm) using 5 mmol/L ammonium acetate solution (pH
      7.5)-acetonitrile (75: 25, v/v) as the mobile phase. The mass spectrometric
      acquisition was carried out by means of electrospray ionization in positive mode
      (ESI+) with multiple reaction monitoring (MRM) method. The good linearities (r2 >
      0.995) were achieved within the ranges of 0.5 - 200 microg/L and 1 - 200 microg/L
      for aristolochic acids A and B, respectively. The limits of detection (LODs) were
      5 microg/kg for aristolochic A and 7.5 microg/kg for aristolochic B, and the
      limits of quantification (LOQs) were 12.5 microg/kg and 25 microg/kg,
      respectively. The recoveries of aristolochic acids A and B at the spiked levels
      of 100 microg/kg and 500 microg/kg ranged from 60.3% to 96.4% with the relative
      standard deviations (RSDs) not more than 10.2%. The results demonstrated that the
      proposed method is efficient, sensitive, reproducible, reliable and suitable for
      the trace determination of aristolochic acids A and B in Chinese herbals and
      traditional Chinese patent medicines.

PMID- 22393695
TI  - [Determination of 10 sedative-hypnotics in human plasma using pulse splitless
      injection technique and gas chromatography-mass spectrometry].
AB  - A simple, precise and sensitive gas chromatography-mass spectrometry (GC-MS)
      method coupled with pulse splitless injection technique was developed for the
      determination of 10 sedative-hypnotics (barbital, amobarbital, phenobarbital,
      oxazepam, diazepam, nitrazepam, clonazepam, estazolam, alprazolam, triazolam) in
      human plasma. The drugs spiked in plasma were extracted with ethyl acetate after
      alkalization with 0.1 mol/L NaOH solution. The organic solvent was evaporated
      under nitrogen stream, and the residues were redissolved by ethyl acetate. The
      separation was performed on an HP-5MS column (30 m x 250 microm x 0.25 microm).
      The analytes were determined and identified using selected ion monitoring (SIM)
      mode and scan mode, respectively. The internal standard method was used for the
      determination. The target analytes were well separated from each other on their
      SIM chromatograms and also on the total ion current (TIC) chromatograms. The
      blank extract from human plasma gave no peaks that interfered with all the
      analytes on the chromatogram. The calibration curves for 10 sedative-hypnotics
      showed excellent linearity. The correlation coefficients of all the drugs were
      higher than 0.9954. The recoveries of the drugs spiked in human plasma ranged
      from 92.28% to 111.7%, and the relative standard deviations (RSDs) of intra-day
      and inter-day determinations were from 4.09% to 14.26%. The detection limits
      ranged from 2 to 20 microg/L. The method is simple, reliable, rapid and sensitive
      for the determination and the quantification of 10 sedative-hypnotics in human
      plasma and seems to be useful in the practice of clinical toxicological cases.

PMID- 22393696
TI  - [Preparation and evaluation of amylose and cellulose tris (3
      trifluoromethylphenylcarbamates)-based chiral stationary phases].
AB  - To broaden the category of polysaccharide-based chiral stationary phases (CSPs),
      coated CSPs based on tris (3-trifluoromethylphenylcarbamates) of amylose and
      cellulose were prepared for enantioseparation in high performance liquid
      chromatography. Their performances were evaluated by eight racemates using hexane
      isopropanol as mobile phase. Compared with the most widely used, commercially
      available polysaccharide-based CSPs, Chiralpak AD and Chiralcel OD, utilizing
      tris (3,5-dimethylphenylcarbamates) of amylose and cellulose as the chiral
      selector, respectively, the obtained CSPs exhibited lower enantioseparation
      abilities. However, cellulose tris(3-trifluoromethylphenylcarbamate)-based CSP
      exhibited characteristic enantioseparation and some chiral compounds were better
      resolved on this CSP than on Chiral-cel OD. The chiral recognition abilities of
      the obtained CSPs were increased with the decrease of the portion of isopropanol
      in the mobile phase and relatively high enantioseparation was obtained with the
      mobile phase of hexane-isopropanol (95: 5, v/v). The obtained amylosic phase
      demonstrated slightly higher chiral resolving ability than the cellulosic one for
      the test racemates. In addition, it was revealed that the enantioseparations of
      the cellulosic and amylosic CSPs were complementary.

PMID- 22393697
TI  - [Retention mechanism of benzoic acid on p-tert-butyl-calix [4] arene-1,2-crown-4
      stationary phase].
AB  - The chromatographic behaviors of benzoic acid (BAH) were investigated on a self
      made p-tert-butyl-calix [4] arene-1,2-crown-4 (Cx4-4) stationary phase by
      changing methanol content and pH value of the mobile phase. The results show that
      hydrophobic interaction is the main interaction in the separation of benzoic
      acid, moreover, inclusion interaction, pi-pi and hydrogen bonding interactions
      also play additional roles. A Density Functional Theory (DFT) method with the
      base set of B3LYP/STO-3G* was employed to explain the interaction between BAH and
      Cx4-4, and the optimized supramolecular structure (Cx4-4 and BAH), the Gibbs free
      energy change (delta G) and stabilization energy change (delta E) were obtained.
      With the assistance of quantum chemistry calculation, the separation mechanism is
      further discussed. The quantum chemical calculation results were consistent with
      the retention behavior of BAH on Cx4-4 stationary phase. Finally, by using the
      self-made Cx4-4 column, a high performance liquid chromatographic (HPLC) method
      for the analysis of BAH in tuber mustard and vinegar was developed.

PMID- 22393698
TI  - [Determination of niclosamide ethanolamine residue in rice and paddy field by
      high performance liquid chromatography].
AB  - A high performance liquid chromatographic (HPLC) method was established for the
      analysis of niclosamide ethanolamine residue in rice and paddy field. The paddy
      water and plant were extracted with alkaline ethylacetate, while the paddy soil,
      rice husk and unpolished rice were first extracted with alkaline ethanol, and
      then with ethylacetate. The extracts were then cleaned-up by a Florisil column
      and detected by high performance liquid chromatography with an ultraviolet
      detector (UVD) on a Welchrom C18 column (250 mm x 4.6 mm, 5 microm). The
      calibration curve showed good linearity from 0.01 mg/L to 10.00 mg/L with the
      correlation coefficient more than 0. 999 8. The average recoveries of this method
      were from 93.47% to 100.9% with the relative standard deviations of 1.46% - 5.82%
      at the spiked levels of 0.01 - 5.00 mg/kg. This method is fast, simple,
      sensitive, reproducible and practical for the determination of niclosamide
      ethanolamine residue in paddy fields, and can meet the requirement of the
      determination of pesticide residues.

PMID- 22393699
TI  - [Determination of trigonelline in coffee powder and instant coffee by ultrasonic
      extraction and high performance liquid chromatography].
AB  - A method of high performance liquid chromatography was established for the
      analysis of trigonelline in coffee powder and instant coffee. The separation was
      performed on a BondPak NH2 column (250 mm x 4.6 mm, 5 microm). The mobile phase
      was methanol-water (82: 18, v/v) at a flow rate of 0.8 mL/min. The detection
      wavelength was set at 260 nm. The method had good linearity in the range of 1 -
      40 mg/L (the correlation coefficient was 0.9998). The repeatability of the method
      was performed at one day, different days, and by two analysts. The accuracy of
      the method was evaluated by recovery study. The recoveries were more than 90%
      with the relative standard deviations less than 3%. The contents of trigonelline
      in samples were assessed with ultrasonic extraction and hot water extraction,
      separately, and the regression coefficient between trigonelline contents obtained
      under the two extraction methods was 0.9964. The method is simple, rapid, highly
      sensitive, and suitable for the analysis of trigonelline and quality control of
      coffee samples.

PMID- 22393700
TI  - [Determination of 5-hydroxytryptamine in plasma by nanofiber solid phase
      extraction-high performance liquid chromatography].
AB  - A novel packed-nanofiber solid phase extraction coupled with high performance
      liquid chromatography-electrochemical detection (HPLC-ECD) method was established
      for the determination of 5-hydroxytryptamine (5-HT) in plasma. A 10% (v/v) HClO4
      solution was used to precipitate the protein in plasma samples. After
      homogenizing for 1 min and centrifuging for 10 min at 12 000 r/min, the
      supernatant was adjusted to pH 8.5 with 0.1 mol/L sodium tetraphenylborate and
      then derivatized with o-phthalaldehyde (OPA) solution at 30 degrees C for 4 min.
      The solution was then purified and preconcentrated by the packed-nanofiber solid
      phase extraction column, in which methanol was used as the eluent. The analyte
      was analyzed by HPLC-ECD. The chromatographic separation was achieved on a
      Shimadzu C18 column with pH 5. 4 0. 05 mol/L phosphate buffer solution
      (containing 0.25 mmol/L ethylene diamine tetraacetic acid)-methanol (60:40, v/v)
      as mobile phase. The linear range was 5 -500 microg/L with the correlation
      coefficient (r2) of 0.9996. The limit of detection (S/N = 3) was 1 microg/L. And
      the spiked recoveries were in the range of 95.6% - 101.4% with the relative
      standard deviations (RSDs) of intra-day and inter-day assays below 5% (n = 3). On
      the basis of the advantages of simplicity, high sensitivity and good
      reproducibility, this method can be used for the determination of 5-HT in human
      plasma.

PMID- 22393702
TI  - [Determination of solubility parameters of high density polyethylene by inverse
      gas chromatography].
AB  - Inverse gas chromatographic (IGC) technology was used to determine the solubility
      parameters of high density polyethylene (HDPE) at the absolute temperatures from
      303.15 to 343.15 K. Six solvents were applied as test probes including hexane (n
      C6), heptane (n-C7), octane (n-C8), nonane (n-C9), chloroform (CHCl3) and ethyl
      acetate (EtAc). Some thermodynamic parameters were obtained by IGC data analysis
      such as the specific retention volumes of the solvents (V(0)(g)), the molar
      enthalpy of sorption (delta H(S)(1)), the partial molar enthalpy of mixing at
      infinite dilution (delta H(1)(infinity)), the molar enthalpy of vaporization
      (delta H(v)), the activity coefficients at infinite dilution (omega
      (1)(infinity)), and Flow-Huggins interaction parameters (X(1,2)(infinity))
      between HDPE and probe solvents. The results showed that the above six probes are
      poor solvents for HDPE. The solubility parameter of HDPE at room temperature
      (298.15 K) was also derived as 19.00 (J/cm3)(0.5).

PMID- 22393701
TI  - [Preparative isolation and purification of five non-volatile compounds from
      Fructus caryophylli and Flos caryophylli by high-speed counter-current
      chromatography].
AB  - A high-speed counter-current chromatographic (HSCCC) method was successfully
      developed for the isolation of three non-volatile compounds from Fructus
      Caryophylli and two chromone compounds from Flos Caryophylli. The optimum
      separation solution systems included system A (n-hexane-ethyl acetate-methanol
      water (5:8:6: 13, v/v/v/v) and system B (n-hexane-ethyl acetate-methanol-water
      (5: 8: 9: 10, v/v/v/v). The upper phase of the system A was used as the
      stationary phase, and the lower phases of the systems A and B as the mobile
      phases were operated at a flow of 1.2 mL/min, while the apparatus rotated at 880
      r/min. The 12.3 mg of ellagic acid, 9.6 mg of rhamnetin, 17.2 mg of quercetin
      were successfully purified from 70 mg of the crude extract of Fructus Caryophylli
      by a two-step separation. In the same way, 10.2 mg of 5,7-dimethoxy-2
      methylchromone, 8.6 mg of 5,7-dimethoxy-2,6-dimethyl-chromone were purified from
      50 mg of the crude extract of Flos Caryophylli. The purities of the compounds
      were all over 96% as determined by high performance liquid chromatography (HPLC).
      The five compounds were indentified by mass spectrometry (MS), 1H-nuclear
      magnetic resonance (NMR) and 13C-NMR. The results indicate that HSCCC is a
      powerful technique for the purification of non-volatile compounds from different
      parts of Eugenia caryophylla Thunb.

PMID- 22393703
TI  - [Determination of seven aromatic amines in hair dyes by capillary electrophoresis
      coupled with field-amplified sample stacking].
AB  - A method for the determination of 4,4'-methylenedianiline, aniline, o-anisidine,
      3, 4-dimethylaniline, p-anisidine, 3-aminophenol, 1-naphthylamine in hair dyes
      was established by capillary electrophoresis coupled with field-amplified sample
      stacking. The optimum running buffer was an aqueous solution containing 0.15
      mol/L NaH2PO4 and 0.015 mol/L trolamine (pH 2.3), and the baseline separation was
      achieved within 6.5 min. The effects of phosphoric acid and acetonitrile
      concentration in the sample matrix, the length of the preinjection water plug,
      and the sample injection voltage and time on the stacking efficiency were
      investigated. The optimum stacking conditions for the real samples included a
      water plug of 3.45 kPa (0.5 psi) x 6 s, the addition of 40% (v/v) acetonitrile
      and 0.6 x 10(-3) mol/L phosphoric acid to the sample solution and a sample
      injection of 10 kV x 10 s. The seven analytes all showed good linearities (R2 >
      0.996) within 3 - 1 000 microg/L, with the detection limits in the range of 0.26 
      2.75 microg/L. The method was shown to provide over 1 - 3 magnitudes of
      sensitivity enhancement. 3-Aminophenol was found in two black hair dyes, and the
      amounts were 7.32 mg/g and 1.34 mg/g, individually. The recoveries ranged from
      74% - 108%. The proposed approach may find widespread applications for the
      determination of trace aromatic amines and other cationic analytes in various
      sample matrixes.

PMID- 22393704
TI  - [Determination of penicillin intermediate and three penicillins in milk by high
      performance capillary electrophoresis].
AB  - A high performance capillary electrophoresis (HPCE) method was developed for the
      simultaneous determination of penicillin intermediate and penicillins in milk,
      including 6-amino-penicillanic acid (6-APA), penicillin G (PEN), ampicillin (AMP)
      and amoxicillin (AMO). The main parameters including the ion concentration and pH
      value of running buffer, separation voltage and column temperature were optimized
      systematically by orthogonal test. The four penicillins (PENs) were baseline
      separated within 4.5 min with the running buffer of 40 mmol/L potassium
      dihydrogen phosphate-20 mmol/L borax solution (pH 7.8), separation voltage of 28
      kV and column temperature of 30 degrees C. The calibration curves showed good
      linearity in the range of 1.56 - 100 mg/L, and the correlation coefficients (r2)
      were between 0.9979 and 0.9998. The average recoveries at three spiked levels
      were in the range of 84.91% - 96.72% with acceptable relative standard deviations
      (RSDs) of 1.11% - 9.11%. The method is simple, fast, accurate and suitable for
      the determination of penicillins in real samples.

PMID- 22393705
TI  - [Determination of forchlorfenuron and gibberellin acid in the grapes using high
      performance liquid chromatography-tandem mass spectrometry].
AB  - A method was established for the determination of two plant growth regulators,
      forchlorfenuron (CPPU)and gibberellin acid (GA3), in the grapes using high
      performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The
      sample was extracted with 0.5% (v/v) formic acid aqueous solution and
      acetonitrile (4: 1, v/v), and cleaned-up with Strata-X solid phase extraction
      cartridge. The separations were performed on an Agilent SB-C18 column (50 mm x
      2.1 mm, 1.8 microm), with a mobile phase of 0.5% formic acid aqueous solution
      acetonitrile at a flow rate of 0.3 mL/min and detected by electrospray ionization
      MS/MS under the multiple reaction monitoring (MRM) mode. The results showed that
      the good linear relationships and the correlation coefficients greater than 0.999
      were obtained. The limits of detection (LODs) were 0.5 microg/L and 0.3 microg/L
      for CPPU and GA3, respectively. The limits of quantification (LOQs) were 2.0
      microg/L and 1.0 microg/L for CPPU and GA3, respectively. The recoveries were
      91.7% - 95.6% and 90.3% - 94.2% with the relative standard deviations (RSD) of
      4.1% - 7.3% and 3.2% - 6.9% for CPPU and GA3, respectively. The results indicate
      that the method is accurate and can be used for the determination of CPPU and GA3
      residues in the grapes.

PMID- 22393706
TI  - [Enantiomeric separation of trantinterol hydrochloride by high performance liquid
      chromatography on cellulose derivative-based chiral stationary phase].
AB  - A high performance liquid chromatographic (HPLC) method using cellulose tris-(3,5
      dimethylphenylcarbamate) as chiral stationary phase (Lux Cellulose-1) for the
      separation of trantinterol hydrochloride enantiomers was developed. The method
      was based on normal phase model with n-heptane as the basal solvent of mobile
      phase. The influences of organic modifiers, mobile phase additives and column
      temperature on the retention and separation of the enantiomers were examined and
      discussed. It was demonstrated that the mobile phase additives had a dominant
      effect on the enantiomeric separation. No separation was observed with the
      addition of diethylamine only in the mobile phase, while the retention was
      increased and the enatiomeric separation was observed with the addition of
      trifluoroacetic acid. When both trifluoroacetic acid and diethylamine were added
      into the mobile phase, the enantioseparation was significantly improved with a
      resolution up to 4.0. Ethanol and isopropanol were investigated as the organic
      modifiers, and ethanol offered a better enatiomeric resolution for trantinterol
      hydrochloride. In the examined temperature range between 15 degrees C and 35
      degrees C both separation factor and resolution were decreased with the increase
      of the column temperature. The optimized chiral HPLC method for the separation of
      trantinterol hydrochloride enantiomers involved a Lux Cellulose-1 column (250 mm
      x 4.6 mm, 5 microm), a mobile phase of n-heptane/ethanol/trifluoroacetic
      acid/diethylamine (88: 12: 0.3: 0.05, v/v/v/v) at a flow rate of 1.0 mL/min, a
      detection at 246 nm and a column temperature of 25 degrees C. The method is
      simple and rapid for the enantiomeric impurity determination of (-)-trantinterol
      hydrochloride bulk samples.

PMID- 22393707
TI  - [Determination of trace carbaryl and carbofuran in water by online column
      enrichment-ultra high performance liquid chromatography].
AB  - An online column enrichment-ultra high performance liquid chromatography (UHPLC)
      method was developed to determine trace carbaryl and carbofuran in water. The
      sample was injected into a UHPLC system directly after filtration with 0.22
      microm membrane, and then enriched by online solid phase extraction (SPE) column.
      The analyte was back-flushed into the analytical column Acclaim RSLC C18 (100 mm
      x 2.1 mm, 2.2 microm) by valve switching method. The mobile phases were 10 mmol/L
      ammonium acetate buffer (pH 5.0, adjusted by acetic acid) and acetonitrile in a
      gradient elution mode with a flow rate of 0.8 mL/min, and detected by a diode
      array detector with the detection wavelength of 280 nm. The good linear ranges of
      carbaryl and carbofuran were 1.0 - 100 microg/L with the correlation coefficients
      (r2) larger than 0.9999, and the limits of detection (S/N = 3) were 0.5 microg/L
      and 0.25 microg/L, respectively. The average spiked recoveries were in the range
      of 76.0% - 120.0%. The method has been applied to determine trace carbaryl and
      carbofuran in water samples with satisfactory results.

PMID- 22393708
TI  - [Progress in improvement of lentiviral vectors' transcriptional read-through].
AB  - Four out of 10 patients of X-linked severe combined immunodeficiency (X-SCID)
      were finally developed leukemia after receiving the treatment of gene therapy
      delivered by gamma-retroviral vectors. This is due to the vector integrated to
      the proximity of lmo2 etc proto-oncogene promoters, leading to the activation of
      onco-gene expression, which raises the concern of the bio-safety of gene therapy
      vectors. Lentiviral vectors, especially self-inactivating lentiviral vectors, are
      considered to be much safer than gamma-retroviral vectors. However self
      inactivating lentiviral vectors also have encountered with some unsafe factors
      and one of them is the problem of transcriptional "read-through" . During the
      past years, achievements have been made to reduce lentiviral vector
      transcriptional read-through, which are reviewed herein.

PMID- 22393709
TI  - [Polyelectrolyte as vehicles for isolation and purification of protein: a
      review].
AB  - Polyelectrolyte with a large number of cations or anions could precipitate the
      oppositely charged proteins to form polyelectrolyte-protein complexes, which then
      aggregated to form larger particles via electrostatic attraction or hydrophobic
      interaction. The precipitation was affected by the molecular weight and
      concentration of the polyelectrolyte as well as the ionic strength and pH of the
      solution. The use of precipitation is an efficient method for selective
      separation of proteins from crude biological mixtures in the downstream processes
      of bioengineering.

PMID- 22393710
TI  - [Preparation and identification of recombinant adenoviruses carrying short
      hairpin RNA targeting parathyroid hormone related protein of goat].
AB  - Parathyroid hormone related protein (PTHrP) has important biological functions in
      calcium metabolism. The aim of this study was to silence the expression of PTHrP
      by RNA interference and recombinant adenovirus, and to provide a material to
      investigate the relative functions of PTHrP in goat mammary gland epithelial
      cell. The Block-iT shRNA interference system was used in this experiment. We
      designed and synthesized two pairs of complementary single-strand DNA
      oligonucleotides (shRNA-322/357) targeting two different sites of PTHrP mRNA.
      Then the oligonucleotides were inserted into shuttle vector pENTR/CMV-GFP/U6.
      After detection of the interference efficiency by Western blotting, we chose
      pENTR/CMV-GFP/U6-322 and adenovirus backbone vector pAD/PL-DEST to produce
      recombinant vector pAD/PL-DEST/CMV-GFP/U6-322. The first generation recombinant
      adenovirus particles (AD-PTHrP-322) were produced and further amplified by
      transfecting HEK-293 cells. The titer of the recombinant adenovirus reached 2.0 x
      1(9) PFU/mL determined by TCID50 assays. The result of real-time quantitative PCR
      indicated that mRNA expression levels of gene were reduced 29.2%, 68.1% and 82.6%
      (P < 0.05), respectively, when goat mammary gland epithelial cells were infected
      with AD-PTHrP-322 after 24, 48 and 72 h, in which PTHrP. Western blotting also
      showed that the expression of PTHrP was reduced by infecting the cells with AD
      PTHrP-322. AD-PTHrP-322 has been proved with significant interference effect on
      expression of PTHrP.

PMID- 22393711
TI  - [Solution structure and antibacterial mechanism of two synthetic antimicrobial
      peptides].
AB  - Mytilin-derived-peptide-1 (MDP-1) and mytilin-derived-peptide-2 (MDP-2) are two
      truncated decapeptides with reversed sequence synthesized corresponding to the
      residues 20-29 of mytilin-1 (GenBank Accession No. FJ973154) from M. coruscus.
      The objective of this study is to characterize the structural basis of these two
      peptides for their antimicrobial activities and functional differences, and to
      investigate the inhibitory mechanism of MDPs on Escherichia coli and Sarcina
      lutea. The structures of MDP-1 and MDP-2 in solution were determined by 1H 2D NMR
      methods; the antibactericidal effects of MDPs on E. coli and S. lutea were
      observed by transmitted electron microscopy (TEM). Both MDP-1 and MDP-2 have a
      well-defined loop structure stabilized by two additional disulfide bridges, which
      resemble the-hairpin structure of mytilin-1 model. The surface profile of MDPs'
      structures was characterized by protruding charged residues surrounded by
      hydrophobic residues. TEM analysis showed that MDPs destroyed cytoplasmic
      membrane and cell wall of bacteria and the interface between the cell wall and
      membrane was blurred. Furthermore, some holes were observed in treated bacteria,
      which resulted in cell death. Structural comparison between MDP-1 and MDP-2 shows
      that the distribution of positively charged amino acids on the loop of MDPs is
      topologically different significantly, which might be the reason why MDP-2 has
      higher activity than MDP-1. Furthermore, TEM results suggested that the
      bactericidal mechanisms of MDPs against E. coli and S. lutea were similar. Both
      MDP-1 and MDP-2 could attach to the negatively charged bacterial wall by
      positively charged amino acid residues and destroy the bacteria membrane in a
      pore-forming manner, thus cause the contents of the cells to release and
      eventually cell death.

PMID- 22393712
TI  - [Expression and functional analysis of OsRboh gene family in rice immune
      response].
AB  - The preliminary role of respiratory burst oxidase homolog (Rboh) in plant immune
      response is defined, but the exact function of OsRboh gene in rice immune
      response and its expression pattern is yet unclear. In order to clarify the role
      of OsRboh in rice immune response, we screened seven OsRboh genes from the latest
      rice genome annotation database. The result of tissue specific expression
      analysis demonstrated that OsRbohD was expressed only in spike and calli, and
      OsRbohE and OsRbohF were only expressed in calli. The rest of OsRboh genes were
      constitutively expressed in rice. In addition, the expression level of OsRboh
      gene family was analyzed in the rice leaves respectively treated with salicylic
      acid (SA), methyl jasmonic acid (MeJA) and Xanthomonas oryzae PV. oryzae (Xoo)
      PXO99 strain by Real-time PCR, and H2O2 content was also quantified by
      spectrophotometry after the three treatments. The result shows that the
      expression of OsRbohA, B, C and D was increased under the treatments of SA, the
      expression of OsRbohA, B, C and G was increased under the treatments of MeJA, and
      the expression of OsRbohA and OsRbohB was induced by Xoo PXO99 strain. However,
      the levels of expression and responsive times of these genes were different.
      Moreover, all three treatments led to H2O2 accumulation. These OsRboh genes have
      functional roles in rice native immune response.

PMID- 22393713
TI  - Morphological, cytological, and molecular characterization of hybrids and their
      progenies derived from the somatic hybridization of Brassica campestris and
      Brassica oleracea.
AB  - In order to produce interspecific somatic hybrids between Brassica campestris (2n
      = 20, AA) and Brassica oleracea (2n = 18, CC), we isolated protoplasts from
      cotyledons and hypocotyls of young seedlings, and fused by 40% polyethylene
      glycol (PEG). Fused cells were cultured in modified K8p liquid medium
      supplemented with 0.2 mg/L 2,4-dichorophenoxyacetic acid (2,4-D) +0.5 mg/L 6
      benzylaminopurine (6-BA)+0.1 mg/L naphthaleneacetic acid (NAA)+ 0.1 mg/L Kinetin
      (Kin), 0.3 mol/L sucrose and 0.3 mol/L glucose were used as osmoticum. At the
      eight-to ten-cell stage, divided cells were transferred to Kao's basal medium
      supplemented with 0.3 mol/L sucrose as carbon source and 0.1% agarose, 2 mg/L 6
      BA+ 2 mg/L Zeatin (ZEA)+1 mg/L NAA+ 0.5 mg/L Kin for callus induction. After 35
      days, when small calli reached 2-3 mm in diameter, calli were transferred to
      regeneration medium containing 5 mg/L Zeatin (ZEA) and 2 mg/L indole-3-acetic
      acid (IAA). After the length of the shoots reached 1-2 cm, the shoots were
      transferred to 1/2 MS+0.2 mg/L NAA for root induction. Morphological, cytological
      and molecular biological analysis methods were used for identification of somatic
      hybrids. The results showed that, the first cell division occurred during 2-7
      days of culture. Five weeks after culture initiation, the plating efficiency
      attained 0.66%. Finally, the shoot regeneration frequency was 3.7%. A total of
      eleven regenerated plants were obtained and verified as somatic hybrids by
      morphological observation and flow cytometry. Cytological studies showed that all
      tested plants had a chromosome number of 38, the sum of both parents. Hybridity
      was also confirmed by randomly amplified polymorphic DNA (RAPD) and genomic in
      situ hybridization (GISH) analysis, indicating that these regenerated plants were
      all true hybrids of B. campestris and B. oleracea. All amphidiploid somatic
      hybrids showed low pollen fertility. Pollen fertility was gradually recovered in
      the first and second progenies.

PMID- 22393714
TI  - [Large-scale in vitro preparation of new gp96 tumor vaccine and analysis of its
      induction of specific anti-tumor immunoresponses].
AB  - Heat shock protein gp96 isolated from tumor tissues holds great promise for tumor
      immunotherapy. However, at present only very limited amount of gp96 protein can
      be isolated from tumor tissues. Here, we reconstituted the yeast-expressed gp96
      (recombinant gp96, rgp96) with B16.F10 melanoma antigens in vitro to prepare new
      gp96 tumor vaccine on large-scale, and analyzed its induction of specific anti
      tumor immunoresponses by ELISPOT, IFN-gamma intracellular staining and
      cytotoxicity assays. Immunization with rgp96-tumor antigen complexes
      significantly inhibited B16 tumor growth compared with either rgp96 or tumor
      antigens alone and led to enhancement of tumor-specific T-cell activities, which
      was found similar to that of tumor tissue derived gp96. Our results therefore may
      provide bases for large-scale preparation of the new generation of gp96 tumor
      vaccines.

PMID- 22393715
TI  - [Effects of extracellular matrix produced in vitro on growth and differentiation
      of MC3T3-E1 cells].
AB  - Extracellular matrix (ECM) keeps cell's shape, protects and nourishes cells; it
      plays a great role in cell proliferation and differentiation. Therefore, ECM is
      very important in cell and tissue engineering. In this study, after primary mouse
      osteoblasts and fibroblasts maintained at confluence in vitro were removed, their
      ECM coated on cell culture plate was prepared, and bone morphogenetic proteins 2
      (BMP-2) was detected in the osteoblasts ECM. MC3T3-E1 preosteoblasts cells were
      seeded on cell culture plates covered with fibroblasts ECM and osteoblasts ECM
      respectively. The proliferative activity of the cells cultured on fibroblasts ECM
      was higher than that on osteoblasts ECM and the control group. The alkaline
      phosphatase activity, relative protein levels of BMP-2 and osteopontin, secreted
      calcium of the cells cultured on osteoblasts ECM were all the highest. The
      results indicate that the two different ECMs produced in vitro had different
      bioactivities, the fibroblasts ECM coated on cell culture plates could accelerate
      MC3T3-E1 cells proliferation, and the osteoblasts ECM could promote cells
      osteogenic differentiation.

PMID- 22393716
TI  - Instability of anthocyanin composition under different subculture conditions
      during long-term suspension cultures of Vitis vinifera L. var. Gamay Freaux.
AB  - The instability of secondary metabolite production is a ubiquitous problem in
      plant cell culture. In order to understand the instability in plant cell culture,
      we investigated anthocyanin accumulation in suspension cultures of Vitis
      vinifera, as a model system, in our laboratory. Not only the anthocyanin contents
      but also its composition exhibited instability along with the long-term
      subculture. New methods were developed to indicate the instability of plant cell
      culture. Both the definition of instability coefficient (delta) and the
      application of factor scores were the first time in this field. To examine the
      effects of culture conditions on instability of anthocyanin biosynthesis,
      different subculture cycles and inoculum sizes had been investigated. Subculture
      cycle and inoculum size were both environmental cues driving the instability.
      Compared with subculture cycle, inoculum size was more effective in working on
      the instability of anthocyanin accumulation. Among all the conditions
      investigated in our study, (6.5 d, 2.00 g), (7 d, 2.00 g), (7.5 d, 2.00 g), (7 d,
      1.60 g) and (7 d, 2.40 g), the condition of 7 d-subculture cycle together with
      1.60 g-inoculum size was the best one to keep the stable production of
      anthocyanins.

PMID- 22393717
TI  - [Site-directed mutagenesis and sulfhydryl PEGylation of lysostaphin].
AB  - The purpose of this paper is to establish sulfhydryl site-directed PEGylation
      method for lysostaphin and to evaluate effects of mutagenesis and modification of
      amino acid residue within putative linker on enzyme activity. On the basis of
      structural analysis of lysostaphin, amino acid 133-154 of tentative linker
      between the N-terminal and C-terminal domain were chosen as the candidate
      residues for site-directed mutagenesis to cysteine. Subsequently, sulfhydryl site
      directed PEGylation was performed by reacting PEG-maleimide reagent with the
      newly introduced cysteine residue of the mutant lysostaphin. The Cys-mutant and
      PEG-modified proteins were both purified, and their enzymatic activity were
      further PEGylated lysostaphins. The mono-PEGylated lysostaphins were separated
      from unmodified lysostaphins through highly efficient one step method with Ni(2+)
      NTA column chromatography. However, both Cys-mutant and PEGylated lysostaphin
      only retained partial activities of the wild-type enzyme. It suggests that
      sulfhydryl site-directed PEGylation modification of the tentative linker between
      the N-terminal and C-terminal domain may affect the catalytic activity of
      lysostaphin.

PMID- 22393718
TI  - [Expression of a protein elicitor pebC1 from Botrytis cinerea in Pichia
      pastoris].
AB  - In order to express PebC1 in Pichia pastoris, the pebC1 sequence was amplified
      from genome Botrytis cinerea BC-4-2-2-1 by PCR and subcloned into the Pichua
      pastoris expression vector pPIC9K to generate pPIC9K-pebC1. The recombinant
      plasmid was linearized by Bgl II and transformed into Pichia pastoris GS115 by
      electroporation. Recombinant Pichia pastoris GS115/pPIC9K-pebC1 was screened by
      MD and G418-YPD plates and further confirmed by PCR. The protein expression was
      induced by methanol and analyzed by SDS-PAGE. SDS-PAGE analysis showed a special
      band about 39 kDa and western blotting indicated a good antigenicity of the
      expressed protein. Bioassay results showed that the recombinant protein PebC1 can
      induce resistance to gray mould disease of cucumber and Arabidopsi thaliana.

PMID- 22393719
TI  - [Strategy for soluble expression of phage-displayed scFv antibody specific for
      zebrafish vitellogenin].
AB  - We developed a new method for soluble expression of phage-displayed scFv antibody
      specific for zebrafish vitellogenin. The scFv antibody F5 could bind zebrafish
      vitellogenin specifically in phage-displayed form but not soluble form. The gene
      of scFv antibody F5 was cloned into vector pET 32a and transferred into
      Escherichia coli ori DE3. With inducible expression, soluble scFv antibody 32a-F5
      was obtained successfully and could also specifically bind to zebrafish
      vitellogenin. The insoluble expression of phage-displayed scFv antibody was a
      common problem in the practical use of phage display. This study offered a
      feasible way to express soluble scFv antibodies with biological activity.

PMID- 22393720
TI  - [Contamination mechanism and regeneration strategies of chromatographic resin in
      separation process for expression product from mammary gland bioreactor].
AB  - This study focused on the contamination mechanism and regeneration strategies of
      sulfopropyl ion exchange resin (SP Sepharose FF) during the separation of
      recombinant human lactoferrin from transgenic bovine milk. We analyzed primary
      constituents' contents in chromatorgraphic material and fractions. The results
      showed that the lipid in milk can clog the column or adhere to the resin through
      hydrophobic interaction, leading to an increase in column pressure. Some casein
      molecules were found to adsorb onto the resin through electrostatic interaction,
      therefore the adsorption capacity was decreased. There was no direct interaction
      between lactose and the resin in the chromatorgraphic process. Increased
      continuous chromatographic cycles and prolonged time interval between protein
      purification and column regeneration could enhance the undesirable interaction
      between the contaminants and resin, thus lowering the regeneration efficiency.
      NaOH was found to be effective in the removal of lipid and casein molecules from
      the column. Furthermore, normal microstructure and chromatographic performance of
      the ion exchanger was recovered after this cleaning procedure.

PMID- 22393721
TI  - [Expression and purification of human beta-secretase (BACE1) in Pichia pastoris].
AB  - To generate active recombinant human beta-secreatase (BACE1) for studying its
      interaction with its inhibitors, we constructed two recombinant plasmids, pPIC9K
      MetBACE22 (bearing pro-bace1 gene) and pPIC9K-MetBACE46 (bearing bace1 gene).
      These two plasmids were then transformed into Pichia pastoris GS115 by
      electroporation to obtain the recombinant strains 9k-B22 and 9k-B46. After
      induction in buffered methanol complex medium, we found the supernatant activity
      of 9k-B22 significantly higher than that of 9k-B46. The culture filtrate of 9k
      B22 was concentrated, and then purified by HisTrap affinity column. The purified
      proteins, showing good BACE1 protease activity, were found to be a mixture of
      glycoproteins because they can be stained by periodic acid-Schiff reagent. After
      this mixture was treated with Endo H(f) (a recombinant protein of endoglycosidase
      H), we found two new adjacent bands around 50 kDa on SDS-PAGE. These two bands
      were cut and subjected to peptide mass fingerprint analysis, and identified as
      proBACE1 and BACE1 proteins. Enzyme assays revealed that the activities of both
      BACE1 proteins in glycosylated and deglycosylated form were lower than that of
      commercial BACE1 (expressed in HEK-293), inferring glycosylation and the type of
      glycosylation are crucial to the activity. However, we found no apparent
      difference in the inhibition of those all above three enzyme forms by one known
      BACE1 inhibitor. This observation demonstrated that the glycosylation of BACE1 by
      Pichia pastoris does not affect its interaction with this inhibitor. After
      optimization of culture conditions, the production of BACE1 in Pichia pastoris
      was enhanced to about 1 mg/L. This work enables us to further investigate the
      interaction of BACE1 and its inhibitors, and assists in discovering and
      optimizing BACE1 inhibitors as anti-Alzheimer's disease agents.

PMID- 22393722
TI  - [Cloning, expression and characterization of gene encoding human stem cell growth
      factor-alpha and its synergetic effect with rhGM-CSF on proliferation of human
      umbilical cord mesenchymal stem cells].
AB  - To investigate the effect of hSCGF-alpha on human Umbilical Cord Mesenchymal Stem
      Cells (hUCMSCs), we obtained hSCGF-alpha using genetic engineering, hSCGF-alpha
      gene was amplified from hUCMSCs cDNA using two-step PCR and was inserted into pET
      28a(+) plasmid vector. Induced by IPTG at 20 degrees Celsius for 24 h, the fusion
      protein expressed in E. coli BL21 (DE3) was mainly existing in soluble form. The
      recombinant hSCGF-a was purified using NI-NTA affinity chromatography and the
      purity was up to 90%. The colony forming test revealed that combined use hSCGF
      alpha and rmGM-CSF (recombinant murine GM-colony stimulating factor, rmGM-CSF)
      had granulocyte/macrophage (GM) promoting effects on murine bone marrow GM
      progenitor. In addition, the results indicated that hSCGF-alpha and rhGM-CSF had
      stimulatory effect on hUCMSCs and their synergetic effect was the strongest.

PMID- 22393723
TI  - [Volatile metabolites analysis and molecular identification of endophytic fungi
      bn12 from Cinnamomum camphora chvar. borneol].
AB  - OBJECTIVE: To identify endophytic fungi bn12 from Cinnamomum camphora chvar,
      borneol and analysis its volatile metabolites. METHOD: The endophytic fungi bn12
      was identified by morphological observation. volatile metabolites of endophytic
      fungi bn12 was analyzed by gas chromatography/mass spectrography (GC-MS). RESULT:
      Volatile metabolites of endophytic fungi bn12 contain borneol and much indoles.
      The ITS sequence of endophytic fungi bnl2 is most similar to the ITS sequence of
      pleosporaceae fungus, particularly C. nisikadoi. CONCLUSION: Endophytic fungi
      bn12 is belong to pleosporaceae fungus. It has the ability of producing broneol.

PMID- 22393724
TI  - [Controling of Paratrioza sinica by bionic glue].
AB  - OBJECTIVE: To investigate the controlling effects of bionic glue on Paratrioza
      sinica. METHOD: P. sinica and bionic glue were chosen as materials to investigate
      the adhesive rate, mortality rate, and study the effects of behavior of P. sinica
      and growth of leaves sprayed with bionic glue. RESULT: Spraying of the bionic
      glue can significantly increase the adhesive rate of P. sinica with no obviously
      repellency, and it can be used to control the adults of P sinaca in field with no
      significant effect on the growth of wolfberry leaves. CONCLUSION: Bionic glue has
      significant controlling effects on adults of P. sinica, it can be used as an
      eliminator of adults of P. sinica in field at the beginning of the vegetation
      season to suppress of the development of P. sinica population.

PMID- 22393725
TI  - [Study on procedure of seed quality testing and seed grading scale of
      Phellodendron amurense].
AB  - OBJECTIVE: To study the procedure of seed quality testing and seed grading scale
      of Phellodendron amurense. METHOD: Seed quality testing methods were developed,
      which included the test of sampling, seed purity, weight per 1 000 seeds, seed
      moisture, seed viability and germination rate. The related data from 62 cases of
      seed specimens of P. amurense were analyzed by cluster analysis. RESULT AND
      CONCLUSION: The seed quality test procedure was developed, and the seed quality
      grading scale was formulated.

PMID- 22393726
TI  - [Effects of different cropping system and fertilization on functional diversity
      in soil microbial community of Chrysanthemum morifolium].
AB  - OBJECTIVE: To study the effects of Chrysanthemum morifolium based on functional
      diversity in soil microbial community with different cropping system and
      fertilization and offer scientific basis for the establishment of the reasonable
      planting patterns. METHOD: Combined yield and quality of Ch. morifolium, 8
      treatments of different cropping system and fertilization on functional diversity
      in soil microbial community of Ch. morifolium were investigated by the Biolog.
      RESULT: The AWCD of Ch. morifolium paddy-dryland rotation was higher than that of
      the continuous cropping, the AWCD of organic fertilizer and compound NPK > single
      organic fertilizer > single compound NPK > no fertilizer. The principal component
      analysis about Ch. morifolium soil microbial carbon source use showed that the
      contribution rate of principal component 1 was 45.5% and principal component 2
      was 12.1%, which could explain most information about the variation. Different
      cropping system of Ch. morfolium differentiated in principal component 1 axis,
      different fertilization differentiated in principal component 2 axis. The yield
      of Ch. morifolium and volatile oil content paddy-dryland rotation was
      significantly higher than that of continuous cropping. CONCLUSION: The Ch.
      morifolium should be cultivated with organic fertilizer and compound NPK by paddy
      dryland rotation patters.

PMID- 22393727
TI  - [Molecular cloning and prokaryotic expression of phenylalanine ammonia-lyase gene
      FdPAL from Fagopyrum dibotrys].
AB  - OBJECTIVE: To clone and characterize the DNA and cDNA sequences of phenylalanine
      ammonia-lyase gene (PAL) from Fagopyrum dibotrys, and investigate the biological
      activity of the obtained PAL. METHOD: Using homology cloning and RT-PCR
      techniques, the DNA and full-length cDNA sequences of PAL gene were amplified
      from F. dibotrys. The obtained sequences were analyzed by bioinformatics
      software. The ORF of PAL gene was cloned into expression vector pET-30b(+) and
      transformed into Escherichia coli BL21 (DE3) for expression the recombined
      protein. The catalytic activity of the recombined protein was determined by
      Spectrophotometer and thin layer chromatography (TLC) methods. RESULT: The DNA
      sequence of PAL gene (designated as FdPAL, GenBank accession number: HM628904)
      was 2 583 bp in size, of which consisted two extrons and a single intron, and the
      full-length cDNA of FdPAL was 2 169 bp in size, which contained an ORF. The
      deduced protein of FdPAL contained 722 amino acids with calculated molecular
      weight (MW) of 78.31 kDa and an isoelectric point (pI) of 5.94. The SDS-PAGE
      results showed that the molecular weight of recombinant FdPAL protein was 75.37
      kDa, which is consistent with the predictions. After 4 hours of induction, the
      enzymatic specific activity of FdPAL reached the summit, up to 4 386 nmol x g(-1)
      x min(-1). The reaction products were also identified by TLC, using L-Phe and
      trans-cinnamic acid as the internal standard. CONCLUSION: The PAL gene (both DNA
      sequence and full-length cDNA sequence) was cloned from F. dibotrys, and it has
      the same classic characters as other PALs in plants. The recombinant FdPAL was
      efficiently expressed in E. coli and had the activity for catalyzing the
      conversion from L-phenylalanine to cinnamic acid.

PMID- 22393728
TI  - [New record for China of host plant of Cynomorium songaricumpeganum multisectum].
AB  - OBJECTIVE: To investigate the distribution and host plants of Cynomorium
      songaricum, and provide a scientific basis for the artificial cultivation of C.
      songaricum and protect the ecological environment in the sandy area. METHOD:
      Specimens of C. songaricum in growing area was collected and accessed according
      to relevant literature and identified. RESULT: The results showed that a new host
      plant of C. songaricum-Peganum multisectum was found. CONCLUSION: A new host
      plant of C. songaricum, Peganum multisectum was reported, and it is provide the
      necessary nutrition for normal growth of C. songaricum.

PMID- 22393729
TI  - [Study of additive properties of total quantum statistical moment of
      chromatographic fingerprint for Buyang Huanwu decoction].
AB  - OBJECTIVE: To study the differences of HPLC fingerprints with the total quantum
      statistical moment for the Buyang Huanwu decoction (BYHWD) processed by various
      ways, and to verify the additive properties of total quantum statistical moment.
      METHOD: The extracts of BYHWD were obtained by water extraction and alcohol
      precipitation firstly, and then were dissolved with five solvents of different
      solubility parameter from 11.4 Cal(1/2) x cm(-3/2) to 23.40 Cal(1/2) x cm(-3/2)
      respectively. Their chromatographic fingerprints were determined by HPLC, finally
      the total quantum statistical moment parameters and its superposition properties
      were manual calculated and analyzed by their expressions. RESULT: As a contrast
      as the whole prescription, the similarities of the various processed samples with
      butanol (11.4 Cal(1/2) x cm(-3/2)), methanol (13.5 Cal(1/2) x cm(-3/2)), 68%
      methanol (16. 67 Cal(1/2) x cm(-3/2)), 34% methanol (20.03 Cal(1/2) x cm(-3/2))
      and distilled water (23.40 Cal(1/2) x cm(-3/2)) were 0. 074, 0. 973, 0. 934, 0.
      991, 0. 993, respectively and while the RSD of these total quantum zero moment,
      center moment and variance of each chromatographic fingerprints for them were
      63.04%, 16.22%, 69.38%, which showed significant difference in these
      chromatographic fingerprints. The total quantum statistical moment parameters of
      the superimposed chromatographic fingerprint with each sole samples were 3.203 x
      10(5) mAu x s, 29.85 min, 389.97 min2, whereas the whole prescription's were
      6.548 x 10(4) mAu x s, 29.44 min, 389.00 min2, that suggested that the absolute
      difference percentages between the superimposed and the whole were 2.209%,
      1.389%, 0.2484%, respectively. CONCLUSION: The total quantum statistical moment
      of the chromatographic fingerprints is of characteristics with additive
      properties, it can be used in static and dynamic quality controlled analyses in
      the Chinese medicine multiple component systems.

PMID- 22393730
TI  - [Optimization of supercritical CO2 extraction of plantaginis semen oil by
      response surface methodology and studies on its antioxidant activity].
AB  - OBJECTIVE: The optimum conditions of SFE-CO2 extraction of Plantaginis Semen oil
      (SPO), the composition of SPO and its antioxidant activities of SPO were all
      investigated in this paper. METHOD: Response surface method (RSM) was used to
      establish the mathematical model of SFE-CO2 extraction of SPO to obtain the
      optimum conditions based on Single factor experiments. Fatty acid compositions
      and contents of SPO were tested by GC-MS, and antioxidant activities of SPO were
      studied by DPPH and ABTS free radical elimination method. RESULT: The optimum
      conditions obtained through RSM analysis were as follows: extraction tempreture
      70 degrees C, extraction pressure 30 MPa, extraction time 120 min and flow rate
      30 L x h(-1). Under the optimal condition, predicted value was 35.91%, while the
      experimental value was 35.07%. The experimental values agree with the predicted
      from the regression model with a relative error less than 5%. The main components
      of SPO were 9,12,15-octadecatrienoic acid, 8,11-octadecadienoic acid,
      octadecanoic acid and hexadecanoic acid. Most of the fatty acids were
      polyunsaturated fatty ones, whose quantities were obtained more than 88%. The
      IC50DPPH and IC50ABTS were 1.13, 3.57 g x L(-1) respectively in DPPH and ABTS
      assay. CONCLUSION: Optimization of the extraction process by RSM of SPO is
      convenient and feasible. SPO has good antioxidant activity and is worth to
      develop for application.

PMID- 22393731
TI  - [Effect of habitat processing method on phillyrin and forsythiaside A of
      Forsythiae Fructus].
AB  - OBJECTIVE: To investigate the habitat processing method of Forsythiae Fructus
      based on the different indexes, and to choose the best habitat producing process.
      METHOD: The habitat producing process was researched by the L9(3(4)) orthogonal
      and the single factor test. The contents of phillyrin and forsythiaside A were
      determined by HPLC. RESULT: The contents of phillyrin and forsythiaside A from
      Forsythiae Fructus processed by evaporating were 1.33-3.05, and 9.71-44.82 mg x
      g(-1), respectively. The contents of phillyrin and forsythiaside A from
      Forsythiae Fructus processed by cooking were 4.63-5.46 mg x g(-1), and 40.20
      64.84 mg x g(-1), respectively. CONCLUSION: With phillyrin and forsythiaside A as
      evaluation indexes, cooking method is superior to evaporate method while it is
      superior to dry method. It is conductive to the preservation and stability of
      phillyrin and forsythiaside A that add 4 times water of material volum and boil
      10 min.

PMID- 22393732
TI  - [Relativity among starch quantity, polysaccharides content and total alkaloid
      content of Dendrobium loddigesii].
AB  - OBJECTIVE: To find out the relativity among starch quantity, polysaccharides
      content and total alkaloid content of Dendrobium loddigesii. METHOD: Microscopy
      counting process was applied to starch quantity statistics, sulfuric acid
      anthrone colorimetry was used to assay polysaccharides content and bromocresol
      green colorimetry was used to assay alkaloid content. Pearson product moment
      correlation analysis, Kendall's rank correlation analysis and Spearman's
      concordance coefficient analysis were applied to study their relativity. RESULT
      AND CONCLUSION: Extremely significant positive correlation was found between
      starch quantity and polysaccharides content, and significant negative correlation
      between alkaloid content and starch quantity was discovered, as well was between
      alkaloid content and polysaccharides content.

PMID- 22393733
TI  - [Study on chemical constituents of Scutelliaria regeliana].
AB  - OBJECTIVE: To study the chemical constituents in ethyl acetate fraction from the
      root of Scutelliaria regeliana. METHOD: The compounds were isolated by silica gel
      column chromatography and HPLC, and their structures were elucidated by means of
      spectral analyses. RESULT: 23 compounds were isolated and identified. CONCLUSION:
      Compound 1 is new, named as scutellariae flavonol, and the others were isolated
      from S. regeliana for the first time.

PMID- 22393734
TI  - [Chemical constituents of endophytic fungus Nodulisporium sp. A4 from Aquilaria
      sinensis].
AB  - OBJECTIVE: To investigate the chemical constituents of an endophytic fungus,
      Nodulisporium sp. A4, from the medicinal plant Aquilaria sinensis and search for
      antitumor natural products. METHOD: The fungus was cultured in liquid medium and
      extracted with EtOAc. The compounds were isolated by various chromatographic
      methods (silica gel, reverse silica gel, Sephadex-LH20, preparative TLC and so
      on) and recrystallization. Structural elucidation was conducted by extensive
      analysis of spectroscopic data as well as by comparison with literature reports.
      The antitumor activity of isolated compounds was tested by MTT method in vitro.
      RESULT: Seven compounds were isolated and identified from the broth culture,
      their structures were determined to be 5-methyl-2-vinyltetrahydrofuran-3-ol (1),
      6-methyl-2-(5-methyl-5-vinyltetrahydrofuran-2-yl) hept-5-en-2-ol (2), 6alpha
      hydroxycyclonerolidol (3), rel-(1S,4S, 5R,7R,10R)-10-desmethyl-1-methyl-11
      eudesmene (4), tyrosol (5), 8-methoxynaphthalen-1-ol (6), and 1,8
      dimethoxynaphthalene (7). Three compounds were isolated and identified from the
      mycelia as ergosterol (8), ergosterol peroxide (9), and cerevisterol (10). The in
      vitro pharmalogical evaluation results displayed that compounds 3 and 4 showed
      89.1%, 44.2% and 82.3%, 79.8% inhibition against tumor cell lines SF268 and NCI
      H460 at 100 mg x L(-1), respectively. CONCLUSION: Compound 1 was a new natural
      product, compounds 2, 3, 7 and 10 were reported from the genus Nodulisporium sp.
      for the first time. Compounds 3 and 4 exhibited weak inhibitory effects on the
      proliferation of tumor cell lines SF268 and NCI-H460.

PMID- 22393735
TI  - [Analysis of chemical components in Aconitum kusnezoffii leaves and their
      extracts by infrared spectroscopy].
AB  - Aconitum kusnezoffi leaves and their extracts were analyzed and evaluated by
      fourier transform infrared spectroscopy, second derivative spectra, and two
      dimensional correlation infrared spectroscopy in this research. There was
      characteristic IR absorption peaks of polyose (767 cm(-1)) in the Aconitum
      kusnezoffii leaves. The IR spectra of the aether extract were similar with the
      ethanol extract of Aconitum kusnezoffi leaves. The strong absorption peaks of
      carbonyl (1 715 cm(-1)) and saturated alkyl groups (2 921, 2 851 cm(-1)) could be
      detected. Some fatty acids were also detected in the water extract. Infrared
      spectroscopy, combined with two dimensional correlation infrared spectroscopy,
      can provide much structural information for herbs, which will benefit the quality
      control, components tracing and identification of extraction process of herbs
      roundly and qualitatively.

PMID- 22393737
TI  - [Determination of o-methylflavinantine in a Tibetan medicine Meconopsis
      quintuplinervia by HPLC].
AB  - OBJECTIVE: To develop an HPLC method for the determination of a Tibetan medicine
      Meconopsis quintuplinervia. METHOD: A Hypersil-Keystone-C18 column (4.6 mm x 250
      mm, 5 microm) was used with the isocratic elution of acetonitrile and 0.012%
      glacial acetic acid. The flow rate was 1.0 mL x min(-1), and the detection
      wavelength was set at 237 nm. RESULT: The linear range of 0-methylflavinantine
      was 0.2-2.4 microg (r = 0.999 7). The average recovery was 96.26%. CONCLUSION:
      The developed method was reliable, and can be used for the quality control of M.
      quintuplinervia Regel.

PMID- 22393738
TI  - [Characteristic chromatographic profile of Zanthoxylum niridum].
AB  - OBJECTIVE: To establish the characteristic fingerprint of Zanthoxylum nitidum by
      HPLC, and to provide a reference for the quality control of Z. nitidum in the
      market. METHOD: The established HPLC characteristic fingerprint of Z. nitidum,
      combined with similarity evaluation and system clustering analysis method, were
      applied to distinguish 25 batches of samples purchased from market preliminarily,
      to identify the authenticity and quality of Z. nitidum ingredients. RESULT: In
      the 25 batches of samples purchased from market, only 8 batches were identified
      as genuine with good quality, 7 batches were identified as defective, 7 batches
      were identified as common counterfeit Toddalia asiatica, and 3 batches were
      identified as counterfeit. CONCLUSION: This method is accurate, convenient and
      reliable. It can be used for identification and quality control of Z. nitidum
      ingredients.

PMID- 22393736
TI  - [Determination of three organic acids in Schisandrae Chinensis Fructus by HPLC].
AB  - OBJECTIVE: To establish an HPLC method for determination of three organic acids
      in Schisandrae Chinensis Fructus. METHOD: The separation was performed on a C18
      column with acetonitrile-15 mmol x L(-1) KH2 PO4 (1:99) and methanol-0.5% acetic
      glacial as the mobile phrase to determine the content of kinic acid, citric acid,
      and protocatechuic acid. RESULT: Three kinds of organic acid can be detective in
      different samples, and the average content of the three organic acids were about
      18%, among which the citric acid was the highest (18%). CONCLUSION: Since organic
      acids is an important parts of the material basis in Schisandrae Chinensis
      Fructus, it is necessary to carry out the pharmacological research associated
      with the function of Schisandrae Chinensis Fructus. Further, it will provide
      scientific basis for the drug relevance research between material basis and
      efficiency, as well as the foundation for the relevance research on the
      properties and Five Tastes of traditional Chinese medicine.

PMID- 22393739
TI  - [UPLC simultaneous determination of five active components in Cinnamomi Ramulus].
AB  - A rapid UPLC method for simultaneous determination of protocatechuic acid,
      coumarin, cinnamic alcohol, cinnamic acid and cinnamaldehyde in Cinnamomi Ramulus
      was established. The optimal conditions of separation and detection were achieved
      on an HSS T3 Column (2.1 mm x 100 mm, 1.8 microm) eluted with a gradient of
      acetonitrile and 0.05% aqueous phosphoric acid, at a flow rate of 0.5 mL x min(
      1), detected at 254 nm. The linear response ranges of protocatechuic acid,
      coumarin, cinnamic alcohol, cinnamic acid and cinnamaldehyde were 0.359-3.59 mg x
      L(-1) (r = 0. 999 3), 2. 834-28.34 mg x L(-1) (r = 0.999 8), 0.574-5.74 mg x L(
      1) (r = 0.999 8), 2.400-24.00 mg x L(-1) (r = 0.999 9), 32.57-325.7 mg x L(-1) (r
      = 0.999 8), respectively (n = 6). The mean recoveries (n = 9) of the five
      components were 96.7%-101.0%, RSD < 2.3%. The assay demonstrates that the method
      has adequate accuracy and selectivity to measure the concentration of
      protocatechuic acid, coumarin, cinnamic alcohol, cinnamic acid and cinnamaldehyde
      in Cinnamomi Ramulus.

PMID- 22393740
TI  - [Study on HPLC fingerprint chromatograms of Arisaematis Rhizoma].
AB  - The fingerprint chromatograms of Arisaematis Rhizoma were established by HPLC.
      The analysis was performed on a Lichrospher C18 (4.6 mm x 200 mm, 5 microm)
      column with acetonitrile-water (containing 0.1% acetic acid) as mobile phase at a
      flow rate of 1.0 mL x min(-1). The detection wavelength was set at 270 nm, and
      the column temperature was 30 degrees C. The similarities of the fingerprint
      chromatograms were calculated over 0.9 between 11 batches of Arisaematis Rhizoma
      samples by analyzing 14 common peaks with adenosine as reference substance.
      However, their fingerprint chromatograms were significantly different from those
      of Pinellia pedatisecta and P. ternate. Adenine, hypoxanthine, xanthine, uridine,
      guanosine, adenosine, schaftoside, and isoschaftoside were identified by
      comparing the retention times and their ultraviolet spectra. The method is
      repeatable, exclusive and can be used for identification and evaluation of
      Arisaematis Rhizoma.

PMID- 22393741
TI  - [Determination of main free amino acids in Banlangen Keli by UPLC].
AB  - OBJECTIVE: To establish a quantitative method with precolumn derivatization for
      determining the contents of six common amino acids in Banlangen Keli by UPLC.
      METHOD: Using 6-acetamido-4-hydroxy-2-methyl quinoline as the derivating agent,
      we determined the contents of arginine, threonine , alanine, gamma aminobutyric
      acid, proline, and valine. The UPLC analysis was performed on a Waters AccQ Tag
      TM Ultra C18 column (2.1 mm x 100 mm, 5 microm) with mobile phase AccQ Tag Ultra
      Eluent A and AccQ Tag Ultra Eluent B gradient elution at a flow rate of 0.7 mL x
      min(-1). The column temperature was 55 degrees C and detection wavelength was 260
      nm. RESULT: The linear ranges of arginine, thremine, alanine, gamma aminobutyric
      acid, proline, and valine were 4. 15549.86 microg (r = 0.999 9), 0.595-5.95
      microg (r = 0.999 8), 0.445-4.45 microg (r = 0. 999 9), 0.515-5. 15 pg (r = 0.999
      9), 8.858-106.3 microg (r = 0.999 9) , 0.585-5. 85 microg (r = 0.999 8). Their
      average recoveries were 100.6%, 98.35%, 100.2%, 98.44%, 98.34%, 98.18% with RSD
      1.8%,1.9%, 2.0%, 2.4%, 1.5% and 2.0%, respectively (n = 6). The contents of amino
      acids were different in samples from five productive enterprises. CONCLUSION: The
      method is efficient, good reproducible, sensitive, and accurate.

PMID- 22393742
TI  - [Effects of schizandrins on learning-memory disorder in mice].
AB  - OBJECTIVE: To observe the effects of schizandrins on the learning and memory
      disorder in mice, and explore its mechanism. METHOD: The memory impairment model
      was established by using the pentobarbital sodium (20 mg x kg(-1))
      intraperitoneally injected in mice. Schizandrins (0.5, 1.0, 2.0 g x kg(-1)) were
      administered through intragavage for consecutive 14 days. Morris Water Maze test
      was used to evaluate the impairment of learning and memory. The energy of
      superoxide dismutase (SOD), nitric oxide (NO) and catalase (CAT) of brain tissue
      were measured. And the positive expression of nuclear transcription factor-kappaB
      p65 (NF-kappaB p65), caspase-3 in the hippocampus CA1 region were determined by
      immunohistochemical analysis. At the cellular level, 24 h after schizandrins
      (0.062 5, 0.125, 0.25 g x L(-1)) were pre-administered, the apoptosis model of
      PC12 cell was induced by H2O2, and activity of PC12 cell was detected by MTT
      colorimetric assay, the energy of NO in cell serum were measured. The expression
      of Bcl-2 was determined by the combination of immunocytochemical staining and
      image analysis software. RESULT: Morris Water Maze test showed that the model
      group mice took shorter searching time and distance on the previous flat area
      than those in the control group (P < 0.05), which could be prolonged after
      schizandrins treatment (P < 0.05, P < 0.01). Compared with the control group, the
      level of NO increased while the activity of SOD, CAT decreased in the model group
      (both P < 0.01). After treated with schizandrins, the level of NO significantly
      decreased (P < 0.01), while the activity of SOD increased (P < 0.01).
      Immunohistochemistry analysis showed that the protein expression of NF-kappaB
      p65, Caspase-3 in the hippocampal CA1 region significantly increased after
      modeling, while schizandrins (1.0 g x kg(-1)) can significantly inhibit the
      protein expression of NF-kappaB p65, Caspase-3 (P < 0.05, P < 0.01). Compared
      with the H2O2, model group, schizandrins (0.125, 0.25 g x L(-1)) can
      significantly increased PC12 cell activity and decreased the NO level (P < 0.05,
      P < 0.01), the expression of Bcl-2 in the schizandrins group (0.125, 0.25 g x L(
      1)) was up-regulated. CONCLUSION: Schizandrins could improve the learning-memory
      dysfunction induced by the sodium pentobarbital in mice, and its protective
      mechanism is related to the lowering oxidative damage and inhibiting the cell
      apoptosis through up-regulating the expression of Bcl-2.

PMID- 22393743
TI  - [Effect of down-regulation of GAT-1 on analgesic action of oxysophoridine].
AB  - OBJECTIVE: To study the effect of GABA transporter (GAT-1) on the analgesic
      action of oxysophoridine (OSR) in the central nervous system of mice. METHOD: Hot
      plate test was used to observe and analyze the effect of gamma aminobutyric acid
      and the inhibitor of GAT-1 (NO-711) on the analgesic action of oxysophoridine.
      Real time RT-PCR was used to investigate the influence of OSR on the expression
      of GAT-1 mRNA induced by formalin in spinal cord and brain of mice. RESULT: Both
      GABA (2.0 mg x kg(-1), icv) and NO-711(0.125 mg x kg(-1), icv) enhanced the
      analgesic action of OSR (32.0 mg x kg(-1), iv) in the hot plate test, and the
      latencies was markedly increased (P < 0.05, P < 0.01). OSR (500.0 mg x kg(-1),
      iv) significantly inhibited the expression of GAT-1 mRNA induced by formalin (P <
      0.05). CONCLUSION: GAT-1 was involved in the analgesia effect of OSR and the down
      regulation of GAT-1 mRNA enhanced the analgesic effect.

PMID- 22393745
TI  - [Comparative study on pharmacokinetics of six major alkaloids in Zuojin Wan
      microemulsion based gel and hydrogel].
AB  - OBJECTIVE: To compare the pharmcoknetic parameters of six major alkaloids in the
      two drug delivery system of Zuojin Wan, by LC-MS assaying the six major alkaloids
      plasma concentration. METHOD: The blood samples were collected at different time
      after transdermal administration. The plasma concentration of six major alkaloids
      were detected by LC-MS, then the concentration-time data are modulated by
      software WinNonlin. RESULT: Took the six alkaloids (berberine palmatine coptisine
      jateorhizine evodiamine rutecarpine) as index components, the relative
      bioavailability were 131%, 127%, 108%, 121%, 92%, 109%, respectively, the ratio
      of Ka were 10.5, 5.1, 3.7, 0.8, 1.8, 1.5, respectively. CONCLUSION: The LC-MS can
      be applied in the determination of six major alkaloids plasma concentration. The
      pharmcoknetic parameters indicated that Zuojin Wan microemulsion gel delivery
      system can accelerate the transdermal absorption rate of Zuojin Wan, compared
      with the hydrogel drug delivery system.

PMID- 22393744
TI  - [Effect of different compatibility of Wuji Wan on bile excretion of
      representative ingredient].
AB  - OBJECTIVE: To research the representative ingredient excretion in bile using the
      different compatibilities of Wuji Wan, in order to indicate the regularity of
      compatibility. METHOD: L9 (3(4)) orthogonal design table was used, in addition 9
      simples, altogether 18 compatibilities. After duodenal administration bile at
      different time spot was collected for LC-MS detection. RESULT: The excretion of
      Evodiae Fructus was negative correlated with that of berberine and palmatine in
      bile. The excretion of Paeoniae Radix Alba was positive correlated with that of
      berberine and palmatine in bile. The excretion of Coptidis Rhizoma, Paeoniae
      Radix Alba was negative correlated with that of evodiamine, rutaecarpine;
      meanwhile, the most superior proportion was also caculated which promote the
      representative ingredient excrete from bile. CONCLUSION: Evodiae fructus
      suppresses representative ingredients of Coptidis Rhizoma excrete through bile.
      Paeoniae Radix Alba promote suppresses representative ingredients of Coptidis
      Rhizoma excrete through bile. Coptidis Rhizoma, paeoniae Radix Alba suppresses
      representative ingredients of Evodiae Fructus excrete through bile. Coptidis
      Rhizoma, Evodiae Fructus suppresses representative ingredients of Paeoniae Radix
      Alba excrete through bile.

PMID- 22393746
TI  - [Absorption of flavones in Gegenqinlian decoction and different compatibilities
      in rat everted gut scas].
AB  - OBJECTIVE: Using rat everted gut sacs to investigate the intestinal absorption
      characteristics of flavones in Gegenqinlian decoction and different
      compatibilities. METHOD: In the research, the intestinal absorption mechanism of
      the active ingredients including puerarin, daidzin, liquiritin, scutellarin,
      baicalin and wogonoside in Gegenqinlian decoction were studied; and then the
      influences of different intestinal segments, different drug concentrations on the
      absorption of ingredients were discussed; finally, the absorption characteristics
      of the active compounds in different compatibility were also be compared. RESULT:
      The absorption mode of the six compounds we disscussed was linearity, R2 > 0.9,
      which was consistent with the zero order rate process. The mechanism of
      absorption of puerarin, daidzin, liquiritin and scutellarin across intestinal
      sacs was passive diffusion, while active transportation was also existed. The Ka
      of baicalin and wogonoside increased along with the raising dosage, which
      indicated the passive absorption of the two ingredients. Different parts of the
      intestinal absorption experiments of Gegenqinlian decoction showed that the best
      absorption site of puerarin, daidzin and scutellarin was jejunum; liquiritin and
      baicalin can be absorbed better in colon; and the best absorption part of
      wogonoside was ileum. In the section of comparing the Ka of different
      compatibilities, it was founded that the absorption of puerarin, daidzin,
      liquiritin, baicalin in Gegenqinlian decoction were best; in the four intestinal
      segments, scutellarin and wogonoside were also absorbed best in Gegenqinlian
      decoction except for the duodenum where the best compatibility was Gegenqinlian
      group. CONCLUSION: For ingerdients, there was selective absorption in intestinal
      sacs. The intestinal absorption characteristics of each component in different
      compatibilities were different, however, the Gegenqinlian decoction was the
      optimal.

PMID- 22393747
TI  - [Effects of Tiangou Jiangya capsule on hypertension and hemodynamics in
      anaesthetized dogs].
AB  - OBJECTIVE: To evaluate the effects of Tiangou Jiangya capsule on blood pressure
      and hemodynamics in anesthetized Beagle dogs. METHOD: Anesthetized dogs were
      divided into five groups: Tiangou Jiangya capsule 3-dose groups as 1.6, 3.2, 6.4
      g x kg(-1), positive control group was giving captopril, negative control was
      giving 0.5% CMC-Na, duodenal administration. The blood pressure and hemodynamic
      changes were observed. RESULT: The systolic blood pressure of middle-dose Tiangou
      Jiangya capsule group was significantly reduced at 30 min after administration.
      The systolic blood pressure (SAP) and diastolic blood pressure (DAP) of high-dose
      group of Tiangou Jiangya capsule was significantly reduced at 15 min to 90 min
      after administration. High-dose Tiangou Jiangya capsule can also significantly
      reduce cardiac work (LVW) and total peripheral resistance (TPR). Tiangou Jiangya
      capsule had no significant effect on the other hemodynamic parameters and
      myocardial oxygen consumption. CONCLUSION: Tiangou Jiangya capsule has a
      significant effect on reducing blood pressure, which is related to the reducing
      total peripheral resistance and reducing cardiac work. The result can provide a
      reference to further clarify the Tiangou Jiangya capsule mechanism on reducing
      blood pressure.

PMID- 22393748
TI  - [Influence of Tiangou Jiangya capsule on blood pressure in renovascular
      hypertension rats].
AB  - OBJECTIVE: To observe the effect of Tiangou Jiangya capsule (TJC) on blood
      pressure in renovascular hypertension rats and explore its possible mechanism.
      METHOD: Seventy-two Wistar rats were randomly divided into normal control group,
      model group, captopril group, TJC small, medium and high dose groups. Non
      invasive blood pressure measurement was used to detect the arterial blood
      pressure of rat tails. PRA, Ang II , ALD, 6-Keto-PGF1alpha, ET and TXB2 content
      in blood was measured by radioimmunoassay. NO content in blood was determined by
      method of nitrate reductase. RESULT: The systolic, diastolic and mean pressure
      significantly increased, serum PRA, Ang II , ALD decreased, ET levels
      significantly increased in model group rats. TJC significantly reduced blood
      pressure, improved the plasma renin activity, decreased ET levels and increased
      NO content of model rats. CONCLUSION: TJC can reduce blood pressure of
      renovascular hypertention rats, and the mechanism may be related to its
      regulating lower blood pressure regulation of the secretion of RAAS system and
      improving vascular endothelial function.

PMID- 22393749
TI  - [Effect of Tiangou Jiangya capsule on rabbit aortic strip contraction].
AB  - OBJECTIVE: To observe the effect of Tiangou Jiangya capsule on isolated rabbit
      aortic strips, and to discuss its antihypertensive mechanism. METHOD: The
      isolated rabbit aortic strips were placed in perfusion baths, and induced to
      contract by norepinephrine (NE), KCl and CaCl2 respectively, then Tiangou Jiangya
      capsule extraction was added to observe its effect on the contraction. The effect
      on intracellular Ca2+ dependent contraction and extracellular Ca2+ dependent
      contraction induced by NE were also studied. RESULT: The Tiangou Jiangya capsule
      (1, 3, 5 g x L(-1)) can reduce the largest contract reaction of aortic strips
      induced by NE or CaCl2 (P < 0.01). It can reduce both intracellular Ca2+
      dependent contraction and extracellular Ca2+ dependent contraction induced by NE
      (P < 0.01), and the effect on extracellular Ca2+ dependent contraction is more
      significant. But the Tiangou Jiangya capsule has no significant effect on KCl
      induced contraction. CONCLUSION: Tiangou Jiangya capsule can regulate
      intracellular Ca2+ concentration and help to relax the vascular smooth muscle.
      The mechanism could be regulating the receptor-operated Ca2+ channel. The effect
      on extracellular Ca2+ dependent contraction is more obvious than on intracellular
      Ca2+ dependent contraction induced by NE.

PMID- 22393750
TI  - [Effects of Tiangou Jiangya capsule on blood pressure in spontaneous hypertensive
      rat].
AB  - OBJECTIVE: To investigate the effects of Tiangou Jiangya capsule on blood
      pressure of spontaneous hypertensive rats. METHOD: The 13-14 week SPF rats were
      selected and randomly divided into model groups, the low, middle, high dose of
      Tiangou Jiangya capsule groups, positive control group administrated with
      captopril. Drugs were intragastric administrated once per day, lasting four
      weeks. The blood pressure, heart rate, heart ventricle indexes, urinary volume
      and the level of PRA,angiotensing II (Ang II), aldosterone (ALD) of rats were
      observed. RESULT: The low, middle, high dose of Tiangou Jiangya capsule can
      remarkably reduce the systolic pressure, diastolic pressure and mean arterial
      pressure of spontaneous hypertensive rats (P < 0.05 or P < 0.01). The low, middle
      dose can reduce the heart rate of rats (P < 0.01). The low dose can effectively
      inhibit the left ventricle indexes (P < 0.05). The Tiangou Jiangya capsule has no
      markedly effects on the renin-angiotensin-aldosterone system (RAAS) activity and
      urinary output of rats. CONCLUSION: The results indicate that the Tiangou Jiangya
      capsule has evident effect of lowering blood pressure of rats, which is related
      to reducing heart rate, heart ventricle indexes, and has no effect on the RAAS
      and diuresis.

PMID- 22393751
TI  - [Experimental studies on toxic effects of Tiangou Jiangya capsule].
AB  - OBJECTIVE: To study the acute and chronic toxicity of Tiangou Jiangya capsule.
      METHOD: Tiangou Jiangya capsule was intragastrically administered to mice twice a
      day. The appearance, behavior, mental status, respiratory changes of mice and the
      number of poisoned and dead mice in each group were noted daily for 14
      consecutive days. The amount of weight and feed of survived mice were recorded
      every day. The mice were divided into four groups: the treatment groups (minimum,
      middle, maximum dose of Tiangou Jiangya capsule) and the control group. After
      continuously orally administrated for 6 months, the rats' behavior, weight gain,
      food consumption, indications for hematology, blood biochemistry, urine analysis,
      electrocardiogram, systematic autopsy and histopathology were observed. The above
      physiological indexes were inspected again 1 month after cease of administration.
      RESULT: The oral acute toxicity study of Tiangou Jiangya capsule in mice revealed
      that the maximum dose is 534.86 g x kg(-1), which was 534.86 times the
      recommended human maximum dose in clinical practice. Compared with normal control
      group, no significant differences were observed in rats' behaviors, food-intake,
      electrocardiogram and relative examination indexes among the treatment groups.
      There was no difference of hematology, biochemistry test, urine and
      histopathology. CONCLUSION: The minimum dosage of Tiangou Jiangya capsule is
      relatively safe. It caused weight loss by administrated with the middle and
      maximum dose for 6 months, which should be paid attention in clinical studies.

PMID- 22393752
TI  - [Studies on anti-EV71 virus activity of traditional Chinese medicine and its
      clinical application in treatment of HFMD].
AB  - Hand-foot-and-mouth disease is caused by intestinal virus infection. The viruses
      coxsackie A16 (CA16) and enterovirus 71 (EV71) are the main pathogens. Between
      them, the virus EV71 is more dangerous and easier to cause serious complications,
      which leads to death or disability. Currently, there are no effective antiviral
      drugs to treat EV71 infection. Therefore, developing an effective drug against
      EV71 virus activity is significant. It has a huge potency of screening the anti
      EV71 components and developing the new drugs from the abundant traditional
      Chinese medicines (TCMs). Meanwhile, since hand-foot-and-mouth disease spread in
      Shanghai in 1981, a growing number of reports on TCMs treatment in clinic have
      been published. In addition, most of treatments with various ways are effective,
      which play a positive role on improving clinic treatment and controlling
      diseases. Moreover, special clinic advantages and features of TCMs were obviously
      shown.

PMID- 22393753
TI  - [Research progress of Chinese herbal medicine and traditional Chinese medicine
      resulting in liver injury].
AB  - The adverse reactions caused by Chinese herbal medicine and traditional Chinese
      medicine are reported increased in recent years, among which the acute liver
      injury caused by Chinese herbal medicine accounts for 21.5% of total liver
      injuries. Despite the misuse of traditional Chinese medicine not in accordance
      with differentiation of symptoms and signs, the adverse reaction of Chinese
      herbal medicine itself can't be little to these adverse events. The paper
      summarizes the most common categories of traditional Chinese medicine resulting
      in liver injury, the mechanism, pathological characteristics, clinical symptom of
      liver injury, the reasons of the reaction and how to prevent. The research aims
      to enhance the clinical physician recognition of liver injury caused by Chinese
      herbal medicine, in order to ensure the safe and rational usage of traditional
      Chinese medicine.

PMID- 22393754
TI  - [Research progress on anti-tumor effect of wind medicine].
AB  - Cancer research of Chinese medicine has formed some major fields, such as
      supporting healthy qi, heat clearing-detoxification and eliminating stasis
      activating blood, and has made certain achievements. The "theory of anti-tumor
      effect with wind medicine" described the anti-tumor effects of wind medicine from
      a new view. In this review, and the relevant research was analyzed
      comprehensively. The mechanism and superiority of the anti-tumor effect of wind
      medicine was summarized, and the research problems was also discussed.

PMID- 22393755
TI  - [Exploration on scientific connotation of compatibility of Zuojin Wan based on
      "disease-syndromes-formulas-medicines" binding mode].
AB  - "Disease-syndromes-formulas-medicines" binding mode is benefit to reveal the
      scientific connotation of the compatibility and mechanism of classical
      prescriptions of traditional Chinese medicine (TCM). In this article, Zuojin Wan
      was used as a model prescription, with the etiology and pathogenesis of liver
      fire invading stomach in TCM, and modern pathological and pharmacological
      interpretation, the compatibility, nature-flavour, channel tropism, the active
      substance and pharmacology of Zuojin Wan were explained, in order to reveal the
      compatibility, nature-flavour and channel tropism of Zuojin Wan, and to provide
      ideas for the development of modern compound prescription.

PMID- 22393756
TI  - [Review on community herbal monographs for traditional herbal medicinal
      products].
AB  - This article discusses the characteristics of cmmunity herbal monographs for
      traditional herbal medicinal products and its establishment procedure. It also
      reviews the new development of cmmunity traditional herbal monographs. The
      purpose is to clarify the relationship between cmmunity herbal monographs and
      simplified registration for traditional herbal medicinal product in European
      Union and provide reference to the registration of taditional Chinese mdicinal
      products in Europe.

PMID- 22393757
TI  - [Taxonomy, ecology, and genetics of the yeast Saccharomyces bayanus - new entity
      in science and practice].

PMID- 22393758
TI  - [Reduction of the synthesized ferrihydrite by a binary anaerobic culture of
      Anaerobacillus alkalilacustris and Geoalkalibacter ferrihydriticus upon growth on
      mannitol].

PMID- 22393759
TI  - Structural and metabolic correlation for Bacillus megaterium ACBT03 in response
      to colchicine biotransformation.
AB  - This study aims to evaluate the effects of colchicine on metabolic and structural
      changes in Bacillus megaterium ACBT03, enduring colchicine bioconversion.
      Electron microscopy examination of cells adapted to different concentrations of
      colchicine for its bioconversion to pharmacologically active 3-demethylated
      colchicine, endowed changes in cell shape, decreased cell wall and plasma
      membrane thickness. In line with microscopic studies, lipid and membrane protein
      contents were drastically reduced in bacterial cells adapted to higher
      concentrations of colchicine and resulting into decrease in cell membrane
      thickness. More numbers of polyhydroxybutyrate (PHB) rich inclusion bodies were
      found inside the colchicine adapted cells and presence of higher amount of PHB, a
      carbon source for generation of redox potential, indicates that it might be
      responsible for activation of P450 BM-3 enzyme and plays significant role in
      colchicine demethylation. The presence of dense ribosome like bodies in
      colchicine adapted cells showed higher biosynthesis of P450 BM-3. Reduction in
      cell wall and cell membrane thickness, presence of more inclusion bodies and
      ribosome like masses in colchicine adapted cells were some of the key interlinked
      phenomena responsible for colchicine bioconversion. This is the first study which
      reports that colchicine demethylation process severely affects the structural and
      metabolic functions of the bacteria.

PMID- 22393760
TI  - A natural antisense transcript regulates mucD gene expression and biofilm
      biosynthesis in Pseudomonas aeruginosa.
AB  - Natural antisense transcripts (NATs) are naturally widespread and have very
      important functions in regulating expression of their target genes. In this
      report, we identified a novel NAT, designated mucD-AS, transcribed from the
      opposite strand ofmucD gene locus, which has a pivotal function in regulating the
      biosynthesis of alginate. For the biotechnological and medical significance in
      the study of alginate biosynthesis, we investigated the effect ofmucD-AS on mucD
      expression and alginate biosynthesis, and confirmed mucD-AS can induce biofilm
      formation ofP. aeruginosa significantly. Since alginate has a key function in the
      infection process and acts as virulence factor of P. aeruginosa, we speculate
      mucD-AS may have a regulatory function in this process.

PMID- 22393761
TI  - [Effect of trehalose on sporangiospores viability of the Mucorales fungus
      Blakeslea trispora].

PMID- 22393762
TI  - [Genetic instability of the Ascomycete fungus Podospora anserina induced by the
      process of deep culturing].

PMID- 22393763
TI  - [Ultrastructural cellular alterations of the natronophilic endoevaporite
      cyanobacterium Euhalothece natronophila during fossilization].

PMID- 22393764
TI  - [3' Flanking region analysis of the dichloromethane dehalogenase gene of DCMA
      Methylobacterium dichloromethanicum DM4].

PMID- 22393765
TI  - [Utility of Ribulose-1,5-Biphosphate Carboxylase as a molecular marker for
      evaluation of autotrophic microbial consortia biodiversity in the surface layers
      of the Kulundine steppe soda lakes].

PMID- 22393766
TI  - Deinococcus soli sp. nov., a gamma- and uv-radiation-resistant bacterium from
      north-west China.
AB  - An ionizing- and UV-radiation-resistant bacterial strain, designated ZLM-202T,
      was isolated from an arid soil sample collected from Xinjiang Province, north
      west China. The soil sample was irradiated before serial dilution plating was
      performed using twofold-diluted marine agar. Phylogenetic analysis based on 16S
      rRNA gene sequences indicated that strain ZLM-202T was a member of the genus
      Deinococcus, exhibiting sequence similarities of 86.3-92.2% to the type strains
      of recognized Deinococcus species. Strain-ZLM-202 was strictly aerobic and showed
      optimum growth at 30-37 degrees C and pH 7.0. The major respiratory menaquinone
      was MK-8. The major fatty acids were 16:1 omega7c, 16:0, 15:1 omega6c, 15:0 iso
      and 16:1 omega5c. L-ornithine was detected in its peptidoglycan. The polar lipid
      profile consisted mainly of various unknown phosphoglycolipids,
      aminophospholipids, glycolipids and phospholipids. The DNA G + C content was 65.5
      mol. %. The strain was shown to be extremely resistant to gamma radiation (> 10
      kGy) and UV light (> 600 J m(-2)). On the basis of the phylogenetic,
      chemotaxonomic and phenotypic data, strain ZLM-202T represents a novel species of
      the genus Deinococcus, for which the name Deinococcus soli sp. nov. is proposed.
      The type strain is ZLM-202T (= CCTCC AB 208223T = KCTC 13419T).

PMID- 22393767
TI  - Isolation and characterization of halophilic bacteria from Urmia Lake in Iran.
AB  - Urmia Lake is one of the most permanent hypersaline lakes in the world which is
      threatened by hypersalinity and serious dryness. In spite of its importance no
      paper has been published regarding bacterial community of this lake. Accordingly,
      the present study aimed to investigate the halophilic bacteria in the
      aforementioned lake. In so doing, thirty seven strains were isolated on six
      different culture media. The isolated strains were characterized using phenotypic
      and genotypic methods. Growth of the strains occurred at 2535 degrees C, pH 6-9
      and 7 to 20% (w/v) NaCl indicating that most of the isolates were moderately
      halophiles. Catalase, oxidase and urease activities were found to be positive for
      the majority of the isolates. Phylogenetic analysis based on 16S rRNA gene
      sequences indicated that the isolated bacteria belonged to two major taxa:
      Gammaproteobacteria (92%, including Salicola [46%], Pseudomonas [13.5%],
      Marinobacter [ 11%], Idiomarina [11%], and Halomonas [8%]) and Firmicutes (8%,
      including Bacillus [5%] and Halobacillus [3%]). In addition, a novel bacterium
      whose 16S rRNA gene sequence showed almost 98% sequence identity with the
      taxonomically troubled DSM 3050T, Halovibrio denitrificans HGD 3T and Halospina
      denitrificans HGD 1-3T, each, was isolated. 16S rRNA gene similarity levels along
      with phenotypic characteristics suggest that some of the isolated strains could
      be regarded as potential type strain for novel species, on which further studies
      are recommended.

PMID- 22393768
TI  - [Species composition of acidophilic chemolithotrophic microbial consortia taking
      part in oxidation of arsenogold concentrates from ore deposits].

PMID- 22393769
TI  - [Bacterial viability of lyophilized microorganisms following 50 years of
      storage].

PMID- 22393770
TI  - [Methanol metabolism in the rhizosphere phytosymbiotic organism Methylobacterium
      nodulans].

PMID- 22393771
TI  - [Microbiological and isotope-geochemical studies in steppe soda lakes and saline
      soils of the Western Baikal region].

PMID- 22393772
TI  - [Molecular detection of methanotrophic bacteria in hot springs from the vicinity
      of the Uzon volcano, Kamchatka].

PMID- 22393774
TI  - [Repeated DNA sequences as an engine of biological diversification].
AB  - Several aspects of the functional role of non-protein-coding DNA elements in the
      cell life and taxa evolution were discussed in connection with modern views on
      three-dimensional regulatory network as a basis for life support and evolution.
      In accordance with this problem, the leading role of duplication and
      multiplication of any DNA fragments (from single nucleotides to segmental
      duplications) in origination of genome structure and reshaping were considered in
      relationships with chromatin proteins. By this way the diversities in genome and
      chromosome architectonics leads to diversity of morphogenesis. The regulation and
      plasticity of the genome is determined by the structure, plasticity and evolution
      of genomic satellite and dispersed repetitive elements, which, being tightly
      bound with life phylogeny, result in somatic and inherited changes. Repeated
      sequences take part and perform some epigenetic regulation via repeats
      themselves, their modifications, or via their RNA transcripts. There is a growing
      evidence that the usage of methaphoric designations of protein-noncoding
      sequences as "egoistic, junk or parasitic" are senseless and useless. To the
      contrary, the hypothesis is formulated that the repetitive non-coding DNA part
      could be considered as a main substrate of life, something like a "carcass"
      serving as a basis for protein-coding sequences. The own molecular evolution of
      this carcass defines the pattern of DNA transcription and then evolution of
      structural proteins and morphological differentiation. Genes involved in main
      energetic, "house-keeping" and metabolic processes are forming some kind of the
      protecting envelope for the hereditary material, and also provides the enzymatic
      pathway of replication, transcription and epigenetic regulation.

PMID- 22393773
TI  - [The Pim family of protein kinases: structure, functions and roles in
      hematopoietic malignancies].
AB  - Phosphorylation is the universal regulatory mechanism in key physiological
      processes such as development, cell differentiation, proliferation, survival and
      malignant transformation. In this review we analyze serine/threonine protein
      kinases of the Pim (proviral integration of Moloney virus) family that have been
      initially discovered in experimental lymphomas. We provide data on gene
      structure, evolution, functions and substrates of Pim protein kinases. Focusing
      on Pim-1 as the major isoform, we analyze its role in the biology of
      hematopoietic malignancies. Pim-1 is a pro-proliferative and pro-survival protein
      kinase. It is constitutively active due to autophosphorylation, and its
      downstream partners positively regulate the cell cycle. Pim-1 cooperates with c
      Myc oncoprotein in leukemogenesis; furthermore, Pim-1, like the Akt protein
      kinase, prevents cell death. Thus, Pim kinases are regarded as new therapeutic
      targets. Finally, we present an original test system f or screening of Pim
      inhibitors. In this test system the growth of a genetically engineered
      Escherichia coli strain in the presence of kanamycin is dependent on the
      phosphorylation of aminoglycoside-3' phosphotransferase VIII by Pim-1:
      pharmacological inhibition of this phosphorylation increases the bacterial cell
      lysis.

PMID- 22393775
TI  - [Fusion genes and transcripts in neoplasia].
AB  - Chromosomal rearrangements resulting in the formation of fusion genes are common
      events in carcinogenesis. There are more than 440 known fusion genes found in
      both malignant and benign tumors. The mechanism of transcription induced
      chimerism (TIC) contributes to fusion transcripts in normal human tissues.
      However, there is no clarity about the role of TIC in carcinogenesis. Hybrid
      proteins resulting from chimeric genes regarded as ideal markers which are
      specific for disease entities can be potential targets for the treatment due to
      their key roles in malignant transformation. In some tumors fusion genes may play
      primary role, and in the others may represent an additional mechanism during
      subclonal selection. The aim is to briefly review and discuss the occurrence and
      biologic relevance of chimeric genes in hematologic malignant diseases, sarcomas
      and epithelial neoplasms.

PMID- 22393776
TI  - [Extraribosomal functions of bacterial ribosomal proteins].
AB  - Though their primary role in a cell is to serve as integral components of protein
      synthesis machinery, the ribosome, many of them have functions beyond the
      ribosome (the phenomenon known as moonlighting), acting either as individual
      regulatory proteins or in complexes with other cellular components.
      Extraribosomal activities of some ribosomal proteins have been observed as early
      as in the 1970-1980s. During the last years both a list of r-proteins
      moonlighters and the repertoire of their additional functions beyond the ribosome
      have been greatly expanded, mainly due to newly developed techniques for
      dissecting RNA/DNA-protein or protein-protein interactions within functional
      complexes involved in various cellular processes. In this review, we surveyed
      information on the experimentally proven as well as on presumptive extraribosomal
      functions which may be performed by bacterial r-proteins in a cell.

PMID- 22393777
TI  - Cloning and characterization of trichome-specific promoter of cpr71av1 gene
      involved in artemisinin biosynthesis in Artemisia annua L.
AB  - Artemisinin, a sesquiterpene lactone endoperoxide derived from Artemisia annua L.
      (Asteraceae), is the most effective antimalarial drug. We used two methods:
      genome walking and thermal asymmetric interlaced polymerase chain reaction, to
      isolate the unknown 5'-flanking sequence of the cyp71av1 gene. The subsequent
      sequence analysis using bioinformatics software revealed that there are several
      cis-acting elements inside the cyp71av1 promoter. The 5'-rapid amplification of
      the cDNA ends method was used to determine the transcription start site of the
      cyp71av1 gene. We then mapped it at the 18 base upstream of the ATG initiation
      codon. For simple functional characterization, we built fusion vectors between
      the 5'-deletion promoter and the gas reporter gene. The expression levels of the
      transferred vectors into A. annua L. were analyzed by the transient expression
      way. The beta-glucuronidase assay results indicated that deletion of the region
      to -1551 bp did not lead to much damage in the GUS activity, whereas further
      deletion, to -1155 bp, resulted in a 5.5-fold reduction of GUS activity. In
      stabilized transgenic A. annua L. seedlings we observed that GUS expression was
      restricted to trichomes, which means that the promoter of the cyp71av1 gene is
      trichome-specific. Compared with the constitutive CaMV 35S promoter, which can
      express genes throughout the plant, influence on the trichome system through the
      trichome-specific expression promoter merely imperils plant growth. In addition,
      the promoter of the cyp71av1 gene contains several binding sites for
      transcription factors, which implies that the cyp71av1 promoter responds to more
      than one form of stimulation.

PMID- 22393778
TI  - Mitochondrial DNA evidence of southward migration of Manchus in China.
AB  - The Northeast area of China is a cross region between East Asia and Siberia.
      Although five populations from this area have been studied in maternal lineage,
      little is known about the genetics of other populations. In this study, forty
      seven Manchu individuals were analyzed using a mitochondrial DNA marker, and
      fourteen mitochondrial DNA haplogroups, the representative haplogroups of east
      Eurasian, were identified. All analyses showed that Manchu were close to the
      neighboring populations such as Mongolian, Korean and northern Han Chinese, and
      were far from the other populations who lived in the cradle of Manchu, suggesting
      that the Manchu integrated gradually with natives following its southward
      migration.

PMID- 22393779
TI  - [CARD15 and TLR4 genes polymorphisms in atopic bronchial asthma].
AB  - In order to investigate whether single nucleotide polymorphisms G(+2722)C and
      3020insC in CARD15 gene and Asp299Gly in TLR4 gene contribute to atopic bronchial
      asthma we performed a comparative analysis of alleles and genotypes frequencies
      of these polymorphisms in Russian patients from Moscow. DNA samples from 283
      patients with atopic bronchial asthma and 227 healthy donors were genotyped.
      There were associations neither of G(+2722)C and 3020insC in CARD15 gene and
      Asp299Gly in TLR4 gene with asthma nor of markers of CARD15 gene with asthma
      severity. Haplotype frequency analysis of CARD15 gene polymorphisms did not
      reveal significant difference between groups. However, a strong association was
      found between Asp299Gly and asthma severity. Allele Asp of this marker showed
      association with mild atopic bronchial asthma and allele Gl--with moderate/severe
      asthma = 0.47, 95% CI [0.24-0.93] i OR = 2.12, 95% CI [1.08-4.18] respectively).

PMID- 22393780
TI  - [Analysis of SYT/SSX1 and SYT/SSX2 fusion genes from synovial sarcoma].
AB  - The t(X;18)(p11;q11) translocation has been shown to be the specific alteration
      for synovial sarcomas. The translocation leads to production of chimeric protein
      SYT/SSX by fusion of SYT and SSX genes involved. The expression analysis of
      SYT/SSX1 and SYT/SSX2 chimeric transcripts was performed in formalin-fixed soft
      tissue tumour specimens and the diagnostic validity of immunohistochemistry, FISH
      and RT-PCR methods was compared. The chimeric transcripts were detected in 12
      from 16 synovial sarcomas: 7 SYT/SSX1 and 5 SYT/SSX2 fusion variants; by
      fluorescence hybridization in situ (FISH) the translocation was found in 13 from
      16 sarcoma samples. As synovial sarcoma represents a diagnostically challenging
      group, genetic analysis of translocations and chimeric transcripts is an
      extremely useful confirmatory diagnostic tool providing higher sensitivity than
      immunohistochemistry markers do.

PMID- 22393781
TI  - [Adaptive evolution of the Homo mitochondrial genome].
AB  - Adaptive evolution of 12 protein-coding mitochondrial genes in members of genus
      Homo (Denisova hominin (H. sp. Altai), Neandertals (H. neanderthalensis) and
      modern humans (H. sapiens)) has been evaluated by assessing the pattern of
      changes in the physicochemical properties of amino acid replacements during the
      primate evolution. It has been found that in the Homo molecular adaptation
      (positive destabilizing selection) become apparent in the form of 12 radical
      amino acid replacements accompanied by statistically significant (P < 0.001)
      changes of physicochemical properties that probably had the functional
      consequences. These replacements have occurred on the stage of a common ancestor
      of the Homo (in CO2 and CytB genes) as well as with the appearance of the common
      ancestor of Neandertals and modern humans (in CO1 and ND5 genes). Radical amino
      acid replacements were mainly revealed in the cytochrome c oxidase complex IV and
      cytochrome bc1 complex III, thus coinciding with general trend of increasing of
      non-synonymous changes in mtDNA genes coding subunits of complexes III and IV
      proteins in anthropoid primates.

PMID- 22393782
TI  - Overexpression of AtLEA3-3 confers resistance to cold stress in Escherichia coli
      and provides enhanced osmotic stress tolerance and ABA sensitivity in Arabidopsis
      thaliana.
AB  - Previous studies have shown that the late embryogenesis abundant (LEA) group 3
      proteins significantly respond to changes in environmental conditions. However,
      reports that demonstrate their biological role, especially in Arabidopsis, are
      notably limited. This study examines the functional roles of the Arabidopsis LEA
      group 3 proteins AtLEA3-3 and AtLEA3-4 in abiotic stress and ABA treatments.
      Expression of AtLEA3-3 and AtLEA3-4 is upregulated by ABA, high salinity, and
      osmotic stress. Results on the ectopic expression of AtLEA3-3 and AtLEA3-4 in E.
      coli suggest that both proteins play important roles in resistance to cold
      stress. Overexpression of AtLEA3-3 in Arabidopsis (AtLEA3-3-OE) confers salt and
      osmotic stress tolerance that is characterized during germination and early
      seedling establishment. However, AtLEA3-3-OE lines show sensitivity to ABA
      treatment during early seedling development. These results suggest that
      accumulation of AtLEA3-3 mRNA and/or proteins may help heterologous ABA re
      initiate second dormancy during seedling establishment. Analysis of yellow
      fluorescent fusion proteins localization shows that AtLEA3-3 and AtLEA3-4 are
      mainly distributed in the ER and that AtLEA3-3 also localizes in the nucleus, and
      in response to salt, mannitol, cold, or BFA treatments, the localization of
      AtLEA3-3 and AtLEA3-4 is altered and becomes more condensed. Protein
      translocalization may be a positive and effective strategy for responding to
      abiotic stresses. Taken together, these results suggest that AtLEA3-3 has an
      important function during seed germination and seedling development of
      Arabidopsis under abiotic stress conditions.

PMID- 22393783
TI  - [Detection of KRAS mutations in tumor cells using biochips].
AB  - Somatic mutations in the KRAS gene are important markers of some types of tumors,
      for example, pancreatic cancer, and may be useful in early diagnostics. A biochip
      has been developed which allows determining most frequent mutations in 12, 13 and
      61 codons of the KRAS gene. To increase the sensitivity of the method and to make
      possible the analysis of minor fractions of tumor cells in clinical samples the
      method of blocking a wild type sequence PCR amplification by LNA-oligonucleotides
      has been used. The product of LNA-clamp PCR was further hybridized with
      oligonucleotide probes, immobilized on biochip. Biochip was tested with 42
      clinical DNA samples from patients with pancreatic cancer, mostly ductal
      adenocarcinomas. As reference methods, the RFLP analysis and sequencing were
      used. The developed approach allows detecting somatic mutations in the KRAS gene
      if the portion of tumor cells with mutation is at least 1% of whole cell
      population.

PMID- 22393784
TI  - [The mutational analysis of carbon catabolite repression in filamentous fungus
      Penicillium canescens].
AB  - Penicillium canescens strain F178 is a natural producer of beta-galactosidase and
      endo-1,4-beta-xylanase. The transcription of genes bgaS and xylA, coding for
      these proteins, is subject to carbon catabolite repression. The system for
      selective isolation of regulatory mutants in P. canescens is developed. Two
      strains from the mutant collection are studied in details. It is shown that both
      mutations can be complement by creA gene of P. canescens, encoding global
      regulator of carbon catabolite repression in filamentous fungi. creA(-) alleles
      contain frameshift mutations in C-domain of CreA. Gene xylA is derepressed in
      mutants at transcription level in the presence of D-glucose. A transcription of
      creA gene in mutants is also derepressed proving effect of autoregulation for
      this gene.

PMID- 22393785
TI  - [HIV-1 assembly is initiated by p17 matrix protein].
AB  - HIV-1 matrix protein (MA) is multifunctional structural protein located on N
      terminus of Gag precursor p55 and responsible for its transport to plasma
      membrane, the site of virus assembly. Here, it has been shown that MA is cleaved
      from Gag precursor at early stage of the virus infection and participates in
      virus assembly. MA is transported into the nuclei wherein it associates with
      viral RNA (vRNA). The MA-vRNA complex is transported to plasma membrane. Mutant
      MA which lost its membranotropic signal does not reach plasma membrane and MA
      vRNA complex remains in the nuclei and cytoskeleton. Thus, MA seems to deliver
      vRNA from the nuclei to plasma membrane through cytoskeleton initiating virus
      assembly.

PMID- 22393786
TI  - [Nuclear beta-catenin localization is not sufficient for canonical Wnt signaling
      activation in human meianoma cell lines].
AB  - In most cases, advanced stages of melanoma are practically incurable due to high
      metastatic potential of tumor cells. Multiple observations support the idea that
      aberrations in Wnt signaling pathway play a significant role in melanoma
      development and progression. Canonical Wnt signaling activation results in
      stabilization and accumulation of the major effector molecule called beta
      catenin. Mutations promoting beta-catenin stabilization and, thereby, activation
      of canonical Wnt signaling pathway are frequently found in different cancers, but
      rarely observed in melanomas. Nevertheless, beta-catenin nuclear and cytoplasmic
      accumulation is the feature of many human melanoma cell lines and original
      tumors. That is why, the aim of the investigation was to elucidate the relation
      between beta-catenin intracellular localization and activity status of Wnt
      signaling pathway in human melanoma cell lines. Ten human melanoma cell lines
      were characterized on the basis of the following parameters: canonical Wnt ligand
      expression, intracellular beta-catenin localization, and activity status of
      canonical Wnt signaling pathway. Here, it has been demonstrated that nuclear
      localization of beta-catenin does not always correspond to active status
      canonical Wnt signaling pathway. Moreover, in the majority of cell lines with
      nuclear beta-catenin canonical Wnt signaling can't be activated by exogenous
      expression of an appropriate ligand. Human melanoma cell lines differ in activity
      of canonical Wnt signaling pathway as well as in mechanisms of its regulation.
      Therefore, the pathway-targeted potential antineoplastic therapy requires the
      formation of a "molecular pattern of cancer" for localization of the defect in
      Wnt signaling cascade in the each case.

PMID- 22393787
TI  - [Bacterial synthesis, purification, and solubilization of transmembrane segments
      of ErbB family members].
AB  - A family of epidermal growth factor receptors, ErbB, represents an important
      class of receptor tyrosine kinases, playing a leading role in cellular growth,
      development and differentiation. Transmembrane domains of these receptors
      transduce biochemical signals across plasma membrane via lateral homo- and
      heterodimerization. Relatively small size of complexes of ErbB transmembrane
      domains with detergents or lipids allows one to study their detailed spatial
      structure using three-dimensional heteronuclear high-resolution NMR spectroscopy.
      Here, we describe the effective expression system and purification procedure for
      preparative-scale production of transmembrane peptides from four representatives
      of ErbB family, ErbB1, ErbB2, ErbB3, ErbB4, for structural studies. The
      recombinant peptides were produced in Escherichia coli BL21(DE3)pLysS as C
      terminal extensions of thioredoxin A. The fusion protein cleavage was
      accomplished with the light subunit of human enterokinase. Several (10-30)
      milligrams of purified isotope-labeled transmembrane peptides were isolated with
      the use of a simple and convenient procedure, which consists of consecutive steps
      of immobilized metal affinity chromatography and cation-exchange chromatography.
      The purified peptides were reconstituted in lipid/detergent environment (micelles
      or bicelles) and characterized using dynamic light scattering, CD and NMR
      spectroscopy. The data obtained indicate that the purified ErbB transmembrane
      peptides are suitable for structural and dynamic studies of their homo- and
      heterodimer complexes using high resolution NMR spectroscopy.

PMID- 22393788
TI  - [Characterization of recombinant human HSP70's domains functions and interdomain
      interactions].
AB  - We investigated ATP-ase and peptide-binding activity of recombinant human heat
      shock protein HSP70(A1B), HSC70, and two hybrid proteins derived from those. The
      UV-spectral recorded data was used to characterize conformational rearrangements,
      which were induced by domain replacement or HSP70-peptide interaction. We have
      shown that N-terminal domain dramatically affect substrate specificity of C
      terminal peptide-binding domain. This proposes new hypothesis for HSP70 chaperone
      machinery. The linear dependence between ATP-ase activity and peptide complex
      ratio was found. This relationship could be used for unlabeled peptide-HSP70
      complex quantification.

PMID- 22393789
TI  - [The adaptation of mycoplasmas to stress conditions: features of proteome shift
      in Mycoplasma hominis PG37 under starvation and low temperature].
AB  - Mycoplasma hominis--one of the widely spread mycoplasmas (class Mollicutes),
      associated with the socially significant human diseases and contamination of cell
      cultures. The solution of the problem on controlling M. hominis infections is
      connected with determination of the molecular basis, responsible for mechanisms
      of bacterium survival under unfavorable conditions. As a result of proteomic
      approach (2-DIGE and MALDI TOF/TOF MS) for the first time, 53 M. hominis PG37
      proteins were detected, different abundance of which occurred at cultivating the
      bacterium under stress (starvation and low temperature) conditions. According to
      the classification of proteins by functional category (clusters of orthologous
      groups of proteins--COG), 47 of the 53 proteins of the mycoplasma are involved in
      the fundamental cellular and biochemical processes--translation (12; 22.64%),
      transcription (2; 3.77%), posttranslational modification (7; 13.20%), cell cycle
      control (2; 3.77%), energy production and conversion (6; 11.32%), carbohydrate
      transport and metabolism (3; 5.66%), amino acid transport and metabolism (8;
      15.09%), nucleotide transport and metabolism (6; 11.32%), inorganic ion transport
      and metabolism (1; 1.89%). The functions of six proteins (11.32%) have not been
      found; 24 proteins (45.28%) are the factors of bacterium virulence. M. hominis
      PG37 proteins, the expression modulation of which arises under the unfavorable
      environmental conditions, are the components of adaptation mechanisms of the
      mycoplasma to the stressors and potential targets for controlling infections
      caused by this bacterium.

PMID- 22393790
TI  - [Polymorphism of 5' promotor region of mitochondrial gamma-DNA-polymerase gene in
      human populations].

PMID- 22393791
TI  - Ending the shortage of generic oncology drugs.

PMID- 22393792
TI  - What is the current standard of care for anti-HER2 neoadjuvant therapy in breast
      cancer?
AB  - Neoadjuvant treatment with a sequential anthracycline-taxane-based chemotherapy
      in combination with trastuzumab (Herceptin) is currently a preferred therapy for
      patients with HER2-positive breast cancer. This approach is based on the higher
      pathologic complete response (pCR) of 40% seen with the addition of trastuzumab,
      compared with a 17% pCR with chemotherapy alone. The pCR can be increased to 75%
      with dual HER2-receptor blockade and chemotherapy. Higher pCR rates are found in
      hormone-receptor-negative tumors. Patients with a pCR after chemotherapy and
      trastuzumab showed a significantly better outcome compared with those who did not
      have a pCR. The need for additional or alternate treatment options is great in
      patients who do not achieve a pCR. Addition of lapatinib (Tykerb) or pertuzumab
      (Omnitarg) to trastuzumab is a therapeutic option. Recent findings suggest pCR
      might not be the appropriate surrogate for long-term outcome in patients with
      hormone receptor-positive and HER2-positive tumors.

PMID- 22393793
TI  - Neoadjuvant therapy for HER2-positive early-stage breast cancer: the future is
      almost here.

PMID- 22393794
TI  - Improving therapy for HER2-positive cancers through neoadjuvant studies.

PMID- 22393795
TI  - Controversies in oncologist-patient communication: a nuanced approach to
      autonomy, culture, and paternalism.
AB  - Difficult dialogues with patients facing life-changing decisions are an intrinsic
      part of oncologic practice and a major source of stress. Having a sophisticated
      approach to the concepts of autonomy, paternalism, and culture can help in
      addressing difficult dilemmas that arise around the issues of disclosure and
      decision making. This article addresses some of the most common major challenges
      in oncologist-patient communication with a nuanced approach to the concepts of
      autonomy, paternalism, and culture. It introduces the new concept of"voluntary
      diminished autonomy" and describes the implications this concept has for the
      consent process. It also attempts to bring clarity to common problems and
      misconceptions relating to culture, paternalism, and therapeutic privilege as
      these pertain to the communication practices of oncologists.

PMID- 22393796
TI  - Autonomy versus paternalism in Latin America.

PMID- 22393797
TI  - The changing scenario in oncologist-patient communication: we need to adapt.

PMID- 22393798
TI  - Dealing with ethical dilemmas in oncological communication involving issues of
      culture and autonomy.

PMID- 22393799
TI  - Optimizing outcomes of advanced prostate cancer: drug sequencing and novel
      therapeutic approaches.
AB  - The rapid approval of several novel agents has given prostate cancer patients and
      their treating physicians many new and effective therapeutic options. Three new
      medical therapies were recently approved on the basis of prolonged overall
      survival in castration-resistant prostate cancer patients: sipuleucel-T
      (Provenge), cabazitaxel (Jevtana), and abiraterone acetate (Zytiga).
      Additionally, there are several other promising prostate cancer agents in late
      stage development, including MDV3100, PROSTVAC-VF (Prostvac), orteronel (TAK
      700), and radium-223 chloride (Alpharadin), each with a novel mechanism of
      action. Taken together, we have entered a period of accelerated drug development
      and optimism in the care of advanced prostate cancer. The treatment paradigm for
      these patients is rapidly evolving, with future study needed to define the
      optimal sequencing and potential combinations of these new agents.

PMID- 22393800
TI  - Sequencing of therapies in advanced prostate cancer.

PMID- 22393801
TI  - What to order from the prostate cancer treatment menu?

PMID- 22393802
TI  - Nodal marginal zone B-cell lymphoma: a diagnostic and therapeutic dilemma.
AB  - In the last lymphoma classifications, three types of marginal zone lymphoma (MZL)
      were delineated: extranodal mucosa-associated lymphatic tissue (MALT) lymphoma,
      splenic MZL, and nodal MZL (NMZL). While MALT lymphoma is already well
      characterized and has been extensively studied, the pathogenesis of the other two
      types, especially that of NMZL, remains incompletely understood. The tumor is
      rather uncommon, although it shares morphologic and immunophenotypic similarities
      with the other MZLs. Few series have been published, and the description is quite
      heterogeneous, reflecting the lack of consensus criteria for its diagnosis; the
      ability to develop such criteria is impeded by the absence of specific
      immunological or molecular abnormalities. The disease develops from peripheral
      (mostly cervical) and abdominal lymph nodes, with or without bone marrow and
      blood involvement. How to differentiate NMZL from lymphoplasmacytic lymphoma
      remains a key point of debate. NMZL also represents a therapeutic dilemma, given
      the absence of published large or prospective series. The 5-year overall survival
      as well as the failure-free survival of patients appear to be lower than those of
      patients with extranodal MZL.The aim of this review is twofold: to summarize
      descriptions of the clinical presentation provided in published series in order
      to help clinicians recognize and treat patients, and to discuss diagnostic
      difficulties faced by hematopathologists when dealing with these lesions and
      others in the differential diagnosis that must be distinguished from one another.

PMID- 22393803
TI  - Nodal marginal zone lymphoma: impersonalized medicine.

PMID- 22393804
TI  - Nodal marginal zone lymphoma: what do we really know?

PMID- 22393805
TI  - Speciated arsenic in air: measurement methodology and risk assessment
      considerations.
AB  - Accurate measurement of arsenic (As) in air is critical to providing a more
      robust understanding of arsenic exposures and associated human health risks.
      Although there is extensive information available on total arsenic in air, less
      is known on the relative contribution of each arsenic species. To address this
      data gap, the authors conducted an in-depth review of available information on
      speciated arsenic in air. The evaluation included the type of species measured
      and the relative abundance, as well as an analysis of the limitations of current
      analytical methods. Despite inherent differences in the procedures, most
      techniques effectively separated arsenic species in the air samples. Common
      analytical techniques such as inductively coupled plasma mass spectrometry (ICP
      MS) and/or hydride generation (HG)- or quartz furnace (GF)-atomic absorption
      spectrometry (AAS) were used for arsenic measurement in the extracts, and
      provided some of the most sensitive detection limits. The current analysis
      demonstrated that, despite limited comparability among studies due to differences
      in seasonal factors, study duration, sample collection methods, and analytical
      methods, research conducted to date is adequate to show that arsenic in air is
      mainly in the inorganic form. Reported average concentrations of As(III) and
      As(V) ranged up to 7.4 and 10.4 ng/m3, respectively, with As(V) being more
      prevalent than As(III) in most studies. Concentrations of the organic methylated
      arsenic compounds are negligible (in the pg/m3 range). However because of the
      variability in study methods and measurement methodology, the authors were unable
      to determine the variation in arsenic composition as a function of source or
      particulate matter (PM) fraction. In this work, the authors include the
      implications of arsenic speciation in air on potential exposure and risks. The
      authors conclude that it is important to synchronize sample collection,
      preparation, and analytical techniques in order to generate data more useful for
      arsenic inhalation risk assessment, and a more robust documentation of quality
      assurance/quality control (QA/QC) protocols is necessary to ensure accuracy,
      precision, representativeness, and comparability.

PMID- 22393806
TI  - Polycyclic aromatic hydrocarbon burden in ambient air in selected Niger Delta
      communities in Nigeria.
AB  - The Niger Delta area in Nigeria has major oil producing and refining centers that
      characterized enormous industrial activities, especially in the petroleum sector.
      These industrial processes release different kinds of atmospheric pollutants, of
      which there is paucity of information on their levels and health implications.
      The objective of this study was to determine the ambient levels of polycyclic
      aromatic hydrocarbons (PAHs) in communities of a local government area (Eleme)
      where oil wells, petrochemical installations, a refinery, and a fertilizer
      complex are located. Respirable particulate matter (PM) in air were collected
      using Anderson high-volume sampler with PM with aerodynamic diameter > 10 microm
      (PM10) inlet for collecting filterable, particle-bound PAHs according to standard
      methods. PAHs were analyzed following standard methods for the 16 World Health
      Organization (WHO) prioritized components. The results were compared against the
      levels in another local government area (Ahoada East) with low industrial
      presence. The average total PAH concentration in Eleme of 9.2 microg/m3 was among
      the highest in the world; by contrast, the average concentration in Ahoada East
      was only 0.17 ng/m3. The most prominent PAHs at Eleme were those known to be
      carcinogenic and included benzo(a)pyrene (1.6 x 10(4) ng/m3 at bubu),
      benzo(k)fluoranthene (2.4 x 10(4) ng/m3 at Akpajo where a petrochemical is
      located), pyrene (3.1 x 10(3) ng/m3 at Ogale), and indeno(1,2,3-cd)pyrene (9.1 x
      10(3) ng/m3 at Akpajo). Data from this study emphasize the need for a
      comprehensive source apportionment study and an assessment of the health effects
      of oil production on local communities of Nigeria where no such information
      currently exists.

PMID- 22393807
TI  - An examination of boundary layer structure under the influence of the gap winds
      in Urumqi, China, during air pollution episode in winter.
AB  - Tethered-sonde measurements of atmospheric profiles were performed at Urumuqi,
      capital of the Xinjiang Uyghur Autonomous Region of China, from 29 December 2008
      to 14 January 2009. The data were used to examine the boundary layer structure
      during this severe air pollution period. Diurnal evolution of local wind flow
      near Urumqi was simulated using the fifth-generation Pennsylvania State
      University-National Center for Atmospheric Research (NCAR) Mesoscale Model (MM5).
      Measurements from operational radiosonde data showed that a southeasterly
      elevated low-level jet often intruded upon Urumqi through the middle Tianshan
      Mountain pass to the south of the city. The tethered-sonde measurements showed
      that calm and northwesterly winds prevailed near the surface in Urumqi, whereas
      the southeasterly winds of relatively higher speed were dominant above
      approximately 400 m. Both temperature inversion and humidity inversion frequently
      occured during day and nighttime. Temperature inversion intensity could sharply
      rise as the stronger elevated southeasterly gale (ESEG) happened. Model
      simulations showed that the winds near the surface around Urumqi remained calm
      during nighttime and developed toward the mountains during daytime. As cool
      airflow in the basin confronted the southeasterly winds from the pass in the
      lower layer, they formed a convergence line around Urumqi city, which was not
      favor for dilution of air pollutants.

PMID- 22393808
TI  - Middle-thermophilic sulfur-oxidizing bacteria Thiomonas sp. RAN5 strain for
      hydrogen sulfide removal.
AB  - Hydrogen sulfide (H2S) is one of the most toxic and offensively odorous gases and
      is generated in anaerobic bioreactors. A middle-thermophilic sulfur-oxidizing
      bacterium (SOB), Thiomonas sp. strain RAN5, was isolated and applied for H2S
      removal from both artificial and anaerobically digested gas. When a bioreactor
      containing medium inoculated with RAN5 was aerated continuously with artificial
      gas (containing 100 ppm H2S) at 45 degrees C for 156 hr, the H2S concentration in
      the vented gas was reduced by 99%. This was not affected by the presence of other
      microbes in the bioreactor The H2S removal efficiency of the RAN5 bioreactor for
      anaerobically digested gas was greater than 99% at influent H2S concentrations
      ranging from 2 to 1800 ppm; the efficiency decreased to 90% at influent H2S
      concentrations greater than 2000 ppm. Thiomonas sp. strain RAN5 cannot survive at
      room temperature, and thus its leakage from a wastewater treatment plant would
      not damage sewage systems. These data suggest that Thiomonas sp. strain RAN5 may
      be a useful microorganism for H2S removal.

PMID- 22393809
TI  - Obtaining polycyclic aromatic hydrocarbon concentration ratios and molecular
      markers for residential wood combustion: Temuco, a case study.
AB  - It is known that residential wood combustion (RWC) is an important source of fine
      particle emissions. The purpose of this work was to characterize the chemical
      composition of the particulate matter present in the Temuco urban atmosphere
      during winter, specifically the polycyclic aromatic hydrocarbon (PAH) profile,
      because PAHs are considered to be among the key compounds in particulate matter
      toxicity. During the 2008 winter monitoring campaign, samples of particulate
      matter with aerodynamic diameters of < or = 10 (PM10) and < or = 2.5 (PM2.5)
      microm were taken on days with contamination episodes. Sixteen U.S. Environmental
      Protection Agency (EPA) PAH compounds were extracted with toluene and determined
      by gas chromatography-mass spectrometry (GC-MS). The results show that
      phenantrene was the predominant compound associated with particulate matter at a
      concentration range between 300 and 600 ng m(-3), 18 times higher than the second
      most abundant PAH compound. High-molecular-mass compounds such as
      dibenz[a,h]anthracene, benzo[g,h,i]perylene, and indeno[1,2,3,c,d]pyrene were
      also found, but they were minorities in the set. It was recognized from the PAH
      concentration ratios of the Temuco atmospheric aerosol that the main
      contamination source was in fact residential wood combustion; although not all
      the concentration ratios evaluated match the reported reference values, probably
      due to the kind of biomass used, the characteristics of Chilean heating
      appliances and climate.

PMID- 22393810
TI  - Source attribution for mercury deposition in the contiguous United States:
      regional difference and seasonal variation.
AB  - Quantifying the contribution of emission sources responsible for mercury
      deposition in specific receptor regions helps develop emission control strategies
      that alleviate the impact on ecosystem and human health. In light of the maximum
      available control technology (MACT) rules proposed by U.S. Environmental
      Protection Agency (EPA) and the ongoing intergovernmental negotiation coordinated
      by United Nations Environmental Programme (UNEP) for mercury, the Community
      Multiscale Air Quality Modeling System (CMAQ-Hg) was applied to estimate the
      source contribution in six subregions of the contiguous United States (CONUS).
      The considered source categories include electric generating units (EGU), iron
      and steel industry (IRST), other industrial point sources excluding EGU and IRST
      (OIPM), the remaining anthropogenic sources (RA), natural processes (NAT), and
      out-of-boundary transport (BC). It is found that, on an annual basis, dry
      deposition accounts for two-thirds of total annual deposition in CONUS (474 Mg
      yr(-1)), mainly contributed by reactive gaseous mercury (about 60% of total
      deposition). The contribution from large point sources can be as high as 75% near
      the emission sources (< 100 km), indicating that emission reduction may result in
      direct deposition decrease near the source locations. Out-of-boundary transport
      contributes from 68% (Northeast) to 91% (West Central) of total deposition.
      Excluding the contribution from out-of boundary transport, EGU contributes to
      about 50% of deposition in the Northeast, Southeast, and East Central regions,
      whereas emissions from natural processes are more important in the Pacific and
      West Central regions (contributing up to 40% of deposition). This suggests that
      the implementation of the new EPA MACT standards will significantly benefit only
      these three regions. Emission speciation is a key factor for local deposition.
      The source contribution exhibits strong seasonal variation. Deposition is greater
      in warm seasons due to stronger Hg0 oxidation. However, the contribution from
      anthropogenic sources is smaller in warm seasons because of larger emissions from
      natural processes and stronger vertical mixing that facilitates transport.

PMID- 22393811
TI  - Driver exposure to particulate matter in Bangkok.
AB  - The aims of this study were to determine the particulate matter with aerodynamic
      diameters > or = 2.5 microm (PM2.5) and 2.5-10 microm (PM10-2.5) exposure levels
      of drivers and to analyze the proportion of elemental carbon (EC) and organic
      carbon (OC) in PM2.5 in Bangkok, Thailand. Four bus routes were selected.
      Measurements were conducted over 10 days in August (rainy season) 2008 and 8 days
      in January (dry season) 2009. The mean PM2.5 exposure level of the Tuk-tuk
      drivers was 86 microg/m3 in August and 198 microg/m3 in January. The mean for the
      non-air-conditioned bus drivers was 63 microg/m3 in August and 125 microg/m3 in
      January. The PM2.5 and PM10-2.5 exposure levels of the drivers in January were
      approximately twice as high as those in August. The proportion of total carbon
      (TC) in PM2.5 to the PM2.5 level in August (0.97 +/- 0.28 microg/m3) was higher
      than in January (0.65 +/- 0.13 microg/m3). The proportion of OC in the TC of the
      PM2.5 in August (0.51 +/- 0.08 microg/m3) was similar to that in January (0.65 +/
      0.07 microg/m3). The TC exposure by PM25 in January (81 +/- 30 microg/m3)
      remained higher than in August (56-21 microg/m3). The mean level of OC in the
      PM2.5 was 29 +/- 13 microg/m3 in August and 50 +/- 24 microg/m3 in January. In
      conclusion, the PM exposure level in Bangkok drivers was higher than that in the
      general environment, which was already high, and it varied with the seasons and
      vehicle type. This study also demonstrated that the major component of the PM was
      carbon, likely derived from vehicles.

PMID- 22393812
TI  - A generalized fuzzy linear programming approach for environmental management
      problem under uncertainty.
AB  - In this study, a generalized fuzzy linear programming (GFLP) method was developed
      to deal with uncertainties expressed as fuzzy sets that exist in the constraints
      and objective function. A stepwise interactive algorithm (SIA) was advanced to
      solve GFLP model and generate solutions expressed as fuzzy sets. To demonstrate
      its application, the developed GFLP method was applied to a regional sulfur
      dioxide (SO2) control planning model to identify effective SO2 mitigation polices
      with a minimized system performance cost under uncertainty. The results were
      obtained to represent the amount of SO2 allocated to different control measures
      from different sources. Compared with the conventional interval-parameter linear
      programming (ILP) approach, the solutions obtained through GFLP were expressed as
      fuzzy sets, which can provide intervals for the decision variables and objective
      function, as well as related possibilities. Therefore, the decision makers can
      make a tradeoff between model stability and the plausibility based on solutions
      obtained through GFLP and then identify desired policies for SO2-emission control
      under uncertainty.

PMID- 22393813
TI  - Influence of particle location on the number of charges per charged nanoparticle
      at the outlet of a needle charger.
AB  - This study has investigated numerically the influence of particle location on the
      number of charges per charged particle in the 10-40 nm size range at the outlet
      of a needle charger by simulating flow field, electric field, particle charging,
      and particle trajectory at various conditions. The results show that the total
      (i.e., diffusion + field charging) number of charges per particle increase with
      decreasing ratio values of radial location at the outlet of the charger due to
      the particle position close to the needle tip. It has also been shown that in the
      outlet region of the charger there is a critical radial location at which the
      number of charges per particle is a maximum; this critical radial location
      represents the point at which the charged particle trajectory becomes closest to
      the needle electrode. The maximum value of number of charges increases with
      increasing Reynolds number and slightly increases with decreasing applied voltage
      for particle diameter larger than 20 nm. The maximum number of charges per
      charged nanoparticle increases with increasing particle diameter. In addition,
      the minimum ratio value of radial particle location decreases with increasing
      Reynolds number for various particle diameters.

PMID- 22393814
TI  - Experimental studies of the dilution of vehicle exhaust pollutants by environment
      protecting pervious pavement.
AB  - This study determines whether environment-protecting pervious pavement can dilute
      pollutants immediately after emissions from vehicle. The turbulence-driven dry
      deposition process is too slow to be considered in this aspect. The pavement used
      is the JW pavement (according to its inventors name), a high-load-bearing water
      permeable pavement with patents in over 100 countries, which has already been
      used for more than 8 years in Taiwan and is well suited to replacing conventional
      road pavement, making the potential implementation of the study results feasible.
      The design of this study included two sets of experiments. Variation of the air
      pollutant concentrations within a fenced area over the JW pavement with one
      vehicle discharging emissions into was monitored and compared with results over a
      non-JW pavement. The ambient wind speed was low during the first experiment, and
      the results obtained were highly credible. It was found that the JW pavement
      diluted vehicle pollutant emissions near the ground surface by 40%-87% within 5
      min of emission; whereas the data at 2 m height suggested that about 58%-97% of
      pollutants were trapped underneath the pavement 20 min after emission. Those
      quantitative estimations may be off by +/- 10%, if errors in emissions and
      measurements were considered. SO2 and CO2 underwent the most significant
      reduction. Very likely, pollutants were forced to move underneath due to the
      special design of the pavement. During the second experiment, ambient wind speeds
      were high and the results obtained had less credibility, but they did not
      disprove the pollutant dilution capacity of the JW pavement. In order to track
      the fate of pollutants, parts of the pavement were removed to reveal a micro
      version of wetland underneath, which could possibly hold the responsibility of
      absorbing and decomposing pollutants to forms harmless to the environment and
      human health.

PMID- 22393816
TI  - [Elder care has to be homosexual friendlier].

PMID- 22393815
TI  - Ultrafine particle emission from incinerators: the role of the fabric filter.
AB  - Incinerators are claimed to be responsible of particle and gaseous emissions: to
      this purpose Best Available Techniques (BAT) are used in the flue-gas treatment
      sections leading to pollutant emission lower than established threshold limit
      values. As regard particle emission, only a mass-based threshold limit is
      required by the regulatory authorities. However; in the last years the attention
      of medical experts moved from coarse and fine particles towards ultrafine
      particles (UFPs; diameter less than 0.1 microm), mainly emitted by combustion
      processes. According to toxicological and epidemiological studies, ultrafine
      particles could represent a risk for health and environment. Therefore, it is
      necessary to quantify particle emissions from incinerators also to perform an
      exposure assessment for the human populations living in their surrounding areas.
      A further topic to be stressed in the UFP emission from incinerators is the
      particle filtration efficiency as function of different flue-gas treatment
      sections. In fact, it could be somehow important to know which particle
      filtration method is able to assure high abatement efficiency also in terms of
      UFPs. To this purpose, in the present work experimental results in terms of
      ultrafine particle emissions from several incineration plants are reported.
      Experimental campaigns were carried out in the period 2007-2010 by measuring UFP
      number distributions and total concentrations at the stack of five plants through
      condensation particle counters and mobility particle sizer spectrometers. Average
      total particle number concentrations ranging from 0.4 x 10(3) to 6.0 x 10(3)
      particles cm(-3) were measured at the stack of the analyzed plants. Further
      experimental campaigns were performed to characterize particle levels before the
      fabric filters in two of the analyzed plants in order to deepen their particle
      reduction effect; particle concentrations higher than 1 x 10(7) particles cm(-3)
      were measured, leading to filtration efficiency greater than 99.99%.

PMID- 22393817
TI  - [The Balloons Test for the assessment of visual inattention in psychogeriatric
      patients].
AB  - The Balloons Test is a paper-and-pencil target cancellation task designed to
      detect visual inattention. The test consists of two subtests: subtest A for
      parallel, automatic processing and detection of twenty circles with an adjoining
      vertical line ('balloons') among a much larger number of circles as distractors.
      Subtest B asks for serial and effortful search of twenty circles among balloons.
      Among 191 consecutive participants of a psychogeriatric day care program (mean
      age 78 yr) 28.2% scored below 17 on subtest B, which is indicative of generalized
      visual inattention. Bivariate analyses showed that visual inattention was
      associated with deficiencies on tasks of visuospatial, constructional and
      executive mental control functions. Using multivariate logistic regression
      analysis, two tests of visuospatial perception (clock reading and picture
      description) retained an independent effect in the association with visual
      inattention. Only three participants (1.6%) were unable to take the Balloons
      Test. The results of this clinical study are in favour of the Balloons Test as a
      useful addition to inattention measurement in psychogeriatric patients.

PMID- 22393819
TI  - [Care diagnosis for demented patients living at home. A new concept?].
AB  - OBJECTIVES: In addition to diagnosing the disease, establishing the care needs of
      people suffering from dementia is of paramount importance. Based on a literature
      review and expert advice, a working document has been drawn up in this article to
      determine the care diagnosis of dementia patients living at home. METHOD: The
      components of care diagnosis were listed by means of a systematic literature
      review. The inventory was then further adapted and a working document was
      developed using semi-structured interviews of sixteen professional caregivers and
      two informal carers. RESULTS: The literature on care diagnosis is recent, and
      there are only a few studies with unequivocal results. However, all authors agree
      that making an inventory of the care needs results in better care planning and a
      better quality of life for both patient and informal carer. A synthesis of the
      literature review and semi-structured interviews led to a working document
      proposing the creation of an inventory of the care needs for a dementia patient
      living at home and his/her informal carer during a multidisciplinary
      consultation. CONCLUSION: It is important to determine the care needs of a
      dementia patient living at home and his/her informal carer. The proposed document
      may serve as a guideline during a multidisciplinary consultation.

PMID- 22393818
TI  - [The shrinking brain: result of normal aging or of selection bias in research?].
AB  - The volume of our brain decreases as we age. This has been demonstrated by
      several large studies on normal aging. A recent study indicates, however, that
      the extent of this decline in normal aging probably has been overestimated
      because these studies have included subjects with preclinical disorders. In this
      article, an example from science is used to describe what effect selection bias
      may have on our model of the aging brain.

PMID- 22393820
TI  - Penn medicine prognosis: reduced costs, increased revenue.

PMID- 22393821
TI  - Tropical storm 'ICD-10' has been designated a hurricane.

PMID- 22393822
TI  - Contract variance management: not by software alone.

PMID- 22393823
TI  - Understanding semi-automated RAC reviews.

PMID- 22393824
TI  - Forskolin and derivatives as tools for studying the role of cAMP.
AB  - Forskolin (7beta-acetoxy-1alpha,6beta,9alpha-trihydroxy-8,13-epoxy-labd-14-en-11
      one) is the first main labdane diterpenoid isolated from the roots of the Indian
      Plectranthus barbatus ANDREWS and one of the most extensively studied
      constituents of this plant. The unique character of forskolin as a general
      direct, rapid and reversible activator of adenylyl cyclase not only underlies its
      wide range of pharmacological effects but also renders it as a valuable tool in
      the study of the role of cAMP. The purpose of this review is to provide data
      presenting the utility of forskolin--as a cAMP activator--for studying the
      function of cAMP from different biological viewpoints as follows: 1)
      Investigation on the role of cAMP in various cellular processes in different
      organs such as gastrointestinal tract, respiratory tract, reproductive organs,
      endocrine system, urinary system, olfactory system, nervous system, platelet
      aggregating system, skin, bones, eyes, and smooth muscles. 2) Studies on the role
      of cAMP activation and inhibition to understand the pathogenesis (e.g. thyroid
      autoimmune disorders, leukocyte signal transduction defect in depression, acute
      malaria infection, secretory dysfunction in inflammatory diseases) as well as its
      possibly beneficial role for curing diseases such as the regulation of coronary
      microvascular NO production after heart failure, the attenuation of the
      development or progression of fibrosis in the heart and lungs, the augmentation
      of myo-protective effects of ischemic preconditioning especially in the failing
      hearts after myocardial infarction, the stimulation of the regeneration of
      injured retinal ganglion cells, the curing of glaucoma and inflammatory diseases,
      the reducing of cyst formation early in the polycystic kidney disease, and the
      management of autoimmune disorders by enhancing Fas-mediated apoptosis. 3)
      Studies on the role of cAMP in the mechanism of actions of a number of drugs and
      substances such as the effect of the protoberberine alkaloid palmatine on the
      active ion transport across rat colonic epithelium, the inhibitory effect of
      retinoic acid on HIV-1-induced podocyte proliferation, the whitening activity of
      luteolin, the effect of cilostazol on nitric oxide production, an effect that is
      involved in capillary-like tube formation in human aortic endothelial cells, the
      apoptotic effect of bullatacin, the effects of paraoxon and chlorpyrifos oxon on
      nervous system. Moreover, cAMP was found to play a role in acute and chronic
      exposure to ethanol, in morphine dependence and withdrawal and in behavioral
      sensitization to cocaine as well as in the protection against cisplatin-induced
      oxidative injuries.

PMID- 22393825
TI  - Simultaneous determination of ginsenosides and lignans in Sheng-mai injection by
      ultra-performance liquid chromatography with diode array detection.
AB  - An ultra-performance liquid chromatography (UPLC) method with diode array
      detection was developed for simultaneous analysis of eight ginsenosides
      (ginsenosides Rg1, Re, Rf, Rb1, Rc, Rb2, Rb3, Rd) and one lignan (schizandrin) in
      Sheng-mai injection, a traditional Chinese medicine prescription widely used for
      the treatment of cardiovascular diseases. The chromatographic separation was
      performed on a Waters ACQUITY UPLC HSS T3 column (1.8 microm, 100 mm x 2.1 mm
      i.d.) using a linear gradient elution over 28 min with a mixture of water and
      acetonitrile as the mobile phase. All calibration curves showed good linearity
      (r2 > 0.9998) within the test ranges. Validation proved the repeatability of the
      method was good and recovery was satisfactory. The validated method was
      successfully applied to 12 batches of Sheng-mai injection. The results showed
      that there was a great variation among different samples. Principal component
      analysis (PCA) further proved considerable variations among the samples from
      different factories and suggested that schizandrin, ginsenosides Rb1 and Rg1
      might have the greatest influence on the variation of 12 samples. In conclusion,
      these results demonstrated that the UPLC method proposed was very useful for the
      analysis and quality evaluation of Sheng-mai injection.

PMID- 22393826
TI  - Quantitative evaluation of sparfloxacin binding to urological catheter surfaces.
AB  - Our aim was to apply high-performance liquid chromatography method for
      quantitative evaluation of the total amount of sparfloxacin (SPA) immobilized on
      the surface of the antimicrobial urological catheters. The amounts of SPA bound
      to catheter were determined indirectly on the basis of the differences in SPA
      concentrations before and after the immobilization process (they have been shown
      to vary from 0.11 to 5.66 mg/g of catheter). We estimated the immobilization
      yield, which altered from 14% to 70% depending on the SPA concentration used. As
      in vitro release studies show, the antibiotic binds to the catheter matrix in two
      modes: relatively stable covalent bond and weak non-covalent bond. Antibacterial
      activity of the modified catheter samples with SPA was controlledby using the
      zone of inhibition test against gram positive and gram negative bacteria.

PMID- 22393827
TI  - Chiral separation of bupivacaine hydrochloride by capillary electrophoresis with
      high frequency conductivity detection and its application to rabbit serum and
      pharmaceutical injection.
AB  - Conductivity detection was employed to detect the enantiomers of bupivacaine
      hydrochloride (Bup), which were separated by high performance capillary
      electrophoresis. A computer-aided technique was used to calculate the binding
      energies, and the interaction between Bup enantiomers and cyclodextrins (CDs) is
      preliminarily discussed. Factors affecting the separation efficiency such as the
      types and concentration of chiral selectors, running buffer, pH value, separation
      voltage and capillary inside diameter and length were studied. Under optimized
      conditions, a baseline separation of Bup enantiomers was achieved in less than 15
      min in 4mM NH4Ac-NaAc-HAc (pH 4.00) -0.48mM sulfobutyl ether-beta-cyclodextrin
      running buffer at a separation voltage of 12 kV. The lowest detectable
      concentration was 0.052 microg/mL. The proposed method was applied to chiral
      separation of Bup enantiomers in rabbit serum and pharmaceutical injections.

PMID- 22393828
TI  - Assessment of the percutaneous penetration of indomethacin from soybean oil
      microemulsion: effects of the HLB value of mixed surfactants.
AB  - The objective of this study was to evaluate the influence of the ratios or the
      hydrophile-lipophile balance (HLB) values of Cremophor EL and Span 80 on the
      phase behavior of the O/W microemulsions and the percutaneous absorption and
      penetration of indomethacin microemulsions. The existence of microemulsion
      regions is investigated in quaternary systems composed of soybean oil/Cremophor
      EL and Span 80 (mixed surfactants)/diethylene glycol monoethyl ether
      (cosurfactant)/water by constructing pseudo-ternary phase diagrams at various
      Cremophor EL/Span 80 ratios. In addition, five microemulsion formulations with
      various mixed surfactants HLB values were evaluated by in vitro penetration
      experiments using mouse skin and Franz diffusion cells. The flux and amount of
      indomethacin penetration from 5 microemulsion formulations were significantly
      different from the control, and the enhance ratios ranged from 2.38 to 4.68 and
      2.11 to 4.23, respectively. The HLB value of mixed surfactants in the
      formulations was a principal factor in determining the percutaneous penetration
      of the drug. The flux and amount of drug penetration increased gradually with
      increasing content of the lipophilic surfactant Span 80 and skin retention was
      highest for mixed surfactants with a HLB value of 7.6. Therefore, it is suggested
      that the presence of mixed surfactants was beneficial in the formation of O/W
      microemulsions and enhanced percutaneous penetration of indomethacin.

PMID- 22393829
TI  - Effect of the surfactant on the availability of piroxicam as a poorly
      hydrosoluble drug from suppositories.
AB  - The use of surfactants in suppository formulations has been suggested to improve
      availability of poorly soluble drugs. In the present study, different kinds of
      surfactants have been investigated to clarify the influence on piroxicam release
      from suppositories formulated with both lipophilic and hydrophilic bases. Two
      hydrophilic glucose-derivate surfactants, and a polyoxylglyceride amphiphilic
      surfactant, all with high HLB values, were investigated for their use in
      improving drug availability. The two glucose derivate surfactants reduced drug
      availability from both lipophilic suppositories and hydrophilic formulations,
      according to longer disintegration times and drug micellization. The more complex
      surfactant, a lauroyl macrogolglyceride, showed an increase in piroxicam
      availability from lipophilic suppositories at the higher tested concentrations
      (15% and 20%). Otherwise, when used in hydrophilic formulations, it was less
      effective in promoting drug release and even reduced drug availability.

PMID- 22393831
TI  - Formulation development of a cream containing fennel extract: in vivo evaluation
      for anti-aging effects.
AB  - This study was aimed to formulate and evaluate anti-aging effects of a topical
      cream (w/o emulsion) containig extract of Fennel (Foeniculum vulgare) versus its
      base. Formulation containing 4% concentrated extract of Foeniculum vulgare was
      developed by entrapping in the inner aqueous phase of w/o emulsion and base
      contained no extract. Both the base and formulation were stored under different
      storage conditions to predict their stability. The formulation and base were
      evaluated for effect on skin moisture and transepidermal water loss (TEWL). The
      base showed insignificant while the formulation showed significant effects on
      skin moisture and TEWL. The parameter volume and surface evaluation of living
      skin (SELS) parameters SEr, SEsc, SEsm, SEw were also evaluated and showed a
      significant (p < or = 0.05) decline. The texture parameter energy showed a
      significant increase proving that the formulation possesses potential anti-aging
      effects.

PMID- 22393830
TI  - Preparation, physicochemical characteristics and bioavailability studies of an
      atorvastatin hydroxypropyl-beta-cyclodextrin complex.
AB  - The aim of this study was to improve the solubility, stability and
      bioavailability of amorphous atorvastatin calcium (AT) by complexing it with
      hydroxypropyl-beta-cyclodextrin. The formation of the inclusion complexation was
      identified by molecular modeling, phase solubility diagrams, differential
      scanning calorimetry and X-ray powder diffractometry. Orally Disintegrating
      Tablets (ODT) were then manufactured by direct compression. Apart from improved
      stability compared to pure AT, disintegration time of 27s, hardness of 5 kg and
      favorable mouth feel were achieved. In vitro dissolution tests of the ODT of AT
      inclusion complex exhibited higher dissolution rates than those with pure drug
      and the commercial tablet Lipitor. In vivo bioavailability studies in rats also
      showed shorter T(max), higher C(max) and increased AUC of 4.42 and 1.86 fold
      compared to the plain drug ODT and Lipitor. These results strongly suggest to use
      HP-beta-CD to improve the physicochemical characteristics and bioavailability of
      AT.

PMID- 22393832
TI  - Influence of vitamin E tocopherol polyethylene glycol succinate 1000 on
      intestinal absorption of icariside II.
AB  - In the present study, the Caco-2 monolayer model and a four-site rat intestinal
      perfusion model were used to investigate the effects of vitamin E tocopherol
      polyethylene glycol succinate 1000 (TPGS) on the intestinal absorption of
      icariside II. Icariside II was analyzed by ultra-performance liquid
      chromatography (UPLC). After that its apparent permeability coefficients (Papp)
      and effective permeability (P*(eff)) were calculated. In the Caco-2 cell model,
      Papp values from the apical (AP) to the basolateral (BL) of icariside II were
      increased and its efflux ratios were markedly reduced in the presence of TPGS.
      However, either 0.25 mg/mL or 0.5 mg/mL of TPGS had no significant difference in
      promoting the absorption of icariside II. In four-site rat intestinal perfusion
      model, P*(eff) of icariside II were significantly increased by 0.5 mg/mL of TPGS
      in ileum and colon. The results suggest that TPGS could promote the intestinal
      absorption of icariside II.

PMID- 22393833
TI  - Antibacterial activity of clarithromycin loaded PLGA nanoparticles.
AB  - Novel drug delivery systems such as nanoparticles (NPs) have been proved to
      enhance the effectiveness of many drugs. Clarithromycin is a broad spectrum
      macrolide antibiotic, used in many infectious conditions like upper and lower
      respiratory tract infections, and skin and other soft tissue infections. This
      paper describes the preparation and enhanced in vitro antibacterial activities of
      clarithromycin loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles. A
      modified quasi-emulsion solvent diffusion (MQESD) method was used to prepare
      clarithromycin (CLR) NPs. The antibacterial activity of the NPs was evaluated
      using the agar well diffusion method against Escherichia coli (PTCC 1330),
      Haemophilus influenzae (PTCC 1623), Salmonella typhi (PTCC 1609), Staphylococcus
      aureus (PTCC 1112) and Streptococcus pneumoniae (PTCC 1240). The inhibition zone
      diameters related to each nano formulation were compared with those for untreated
      CLR at the same concentrations. The results indicated that the mean inhibition
      zone diameters of NPs against all the bacteria tested were significantly higher
      than those of untreated CLR, particularly in the case of S. aureus. The increased
      potency of CLR NPs may be related to some physicochemical properties of NPs like
      modified surface characteristics, lower drug degradation, and increased drug
      adsorption and uptake.

PMID- 22393835
TI  - Effect of genetic polymorphism of UCP2-866 G/A on repaglinide response in Chinese
      patients with type 2 diabetes.
AB  - The aim of the present study was to evaluate the impact of the UCP2-866 G/A
      polymorphism on the efficacy of repaglinide in treating patients with diabetes
      mellitus type 2 (T2DM). 370 patients with T2DM and 166 healthy volunteers were
      enrolled to identify UCP2-866 G/A genotypes. 16 patients with GG genotype, 14
      with GA genotype and 11 with AA genotype of UCP2-866 G/A underwent an 8-week
      repaglinide treatment regimen. There were no differences in allele frequency of
      UCP2-866 G/A between T2DM patients and control subjects. The patient with AA
      genotype of UCP2-866 G/A had higher levels of fasting plasma glucose (FPG), 30
      min and 2-h postload plasma glucose, glycated haemoglobin (HbA1c), and lower
      concentrations of 30-min and 2-h postload plasma insulin, homeostasis model
      assessment of beta cell function (HOMA-beta), deltaI30/deltaG30 compared with GG
      genotype. After repaglinide treatment for 8 consecutive weeks, we found that A
      allele carriers of UCP2 in the T2DM patients had smaller decrease in FPG (P <
      0.05) and HbA1c (P < 0.05), and smaller increase in 30-min postload plasma
      insulin (P < 0.01) compared with GG genotypes. We demonstrated that UCP2-866 G/A
      polymorphism is associated with the therapeutic efficacy of repaglinide in
      Chinese T2DM patients.

PMID- 22393834
TI  - Genetic polymorphisms of VKORC1, CYP2C9, CYP4F2 in Bai, Tibetan Chinese.
AB  - BACKGROUND: VKORC1, CYP2C9 and CYP4F2 are three critical genes associated with
      inter-individual variation of warfarin dose. Many dosing algorithms containing
      these gene polymorphisms and demographic characteristics have been set up for
      better use of warfarin. However, with distinct gene mutation frequencies among
      different ethnics, dosing algorithms differ greatly. For Chinese, related
      research just concentrate on Han Chinese, ignoring other Chinese ethnicities.
      This study aims to detect the popular polymorphisms in these three critical genes
      in Bai, Tibetan Chinese, to start the exploration of better use of warfarin in
      Chinese minorities. METHODS: PCR-based methods were used to analyze VKORC1 3673G
      > A, CYP2C9*3, CYP4F2 rs2108622 C > T in Han, Bai and Tibetan Chinese. RESULTS:
      The differences among the mutation frequencies of the studied genes in three
      ethnicities were not statistically significant. The frequency of A-allele of
      VKORC1 3673G > A was 92.8%, 90.2%, 90.8% in Bai, Tibetan, Han Chinese,
      respectively. The frequency of *3-allele in CYP2C9*3 was low in Bai (4.5%),
      Tibetan (2.8%) and Han Chinese (4.6%). Approximately one fourth of each ethnic
      had the mutant T-allele of CYP4F2 rs108622. However, Bai Chinese got
      statistically higher A-allele frequency of VKORC1 3673G > A than previously
      studied Han Chinese did. CONCLUSIONS: Bai Chinese got significant higher A-allele
      frequency of VKORC1 3673G > A.

PMID- 22393836
TI  - Differential efficacy of gefitinib across age groups in treatment of advanced
      lung adenocarcinoma.
AB  - OBJECTIVE: To compare the efficacy of gefitinib monotherapy across different age
      groups of patients with advanced lung adenocarcinoma. METHODS: Clinical data of
      patients (mostly Chinese) with advanced lung adenocarcinoma who were non-smokers
      or light smokers and had received oral gefitinib (250mg/d) between October 2006
      and December 2009 were reviewed retrospectively. The 93 enrolled patients (25
      male and 68 female; median age, 62.5 years), were divided into three age groups:
      < or = 49 years (n = 22), 50-69 years (n = 53), and > or = 70 years (n = 18).
      Among them, 84 patients had received at least one chemotherapy regimen
      previously. The objective response rate (ORR), time to disease progression (TTP),
      median overall survival (MOS) and adverse effects in response to gefitinib
      treatment were analyzed in the above age groups. RESULTS: Out of 93 patients, a
      complete response was seen in 5 patients, partial response in 43 patients, stable
      disease in 36 patients, and disease progression in 9 patients. ORR was 51.6%, and
      the disease control rate (DCR) was 90.3%. No significant correlation was observed
      between ORR of gefitinib treatment and the baseline clinical characteristics of
      the patients. The median TTP was 12.6 months, and median overall survival (MOS)
      was 23.4 months. Gefitinib treatment-related UP was prolonged with increasing
      age: 8.2 months, 14.2 months and 18.2 months in the age groups of < or = 49
      years, 50-69-years and > or = 70-years, respectively (log-rank P = 0.002). MOS in
      the three age groups was 20.4 months, 23.6 months and 22.0 months, respectively
      (P > 0.05). The most common adverse effects were rash and diarrhoea, and rash
      seemed to be correlated with ORR (ORR = 2.631; p = 0.044, 95% CI: 1.025-6.753).
      CONCLUSIONS: In Asian patients with advanced lung adenocarcinoma who were non
      smokers or light smokers and were treated with gefitinib, progression-free
      survival was correlated with age. Elderly patients (> or = 70 years) seemed more
      likely to benefit from gefitinib treatment.

PMID- 22393837
TI  - Efflux transporter mRNA expression profiles in differentiating JEG-3 human
      choriocarcinoma cells as a placental transport model.
AB  - The kinetics of drug transport across the trophoblast layer is determined by
      several factors. Human choriocarcinoma cell lines like BeWo and JEG-3 have been
      used as models of the trophoblast layer to examine the placental transport of
      drugs. Previously, the drugs examined in these models have been readily
      transported across the trophoblast layer via cellular gap junctions. These
      backgrounds enabled us to establish the differentiating JEG-3 cell (DJEG) layer
      model, which suppresses paracellular drug transport, as an evaluation system of
      placental drug transport. The efflux transporters on the trophoblast layer assume
      the meaningful role of protecting the fetus from xenobiotic substances. In order
      to clarify the usefulness of our DJEG placental drug transport model, this study
      examined the mRNA expression profiles of the efflux transporters MRPs, MDR1, and
      BCRP in JEG-3 cells and compared them with those of BeWo cells and their known
      placental expression. We suggest that the mRNA of efflux transporters MRP 1-8 and
      BCRP are expressed widely in JEG-3 cells; however, expression levels of MDR1 mRNA
      were undetectable. It was also indicated that polymorphisms of BCRP C421A in both
      the BeWo and JEG-3 cells are of the wild-type. We demonstrated the efflux
      transporters' expression profiles, as well as those of the BeWo cells, was
      demonstrated in the DJEG placental drug transport evaluating model as well as the
      BeWo cells, in the DJEG placental drug transport evaluation model. Based on these
      findings, we hope that the DJEG model will be adequate for use in evaluating
      placental drug transport in relation to the transporter proteins.

PMID- 22393838
TI  - Pitfalls in cell culture work with xanthohumol.
AB  - Xanthohumol, the most abundant prenylated chalcone in hop (Humulus lupulus L.)
      cones, is well known to exert several promising pharmacological activities in
      vitro and in vivo. Among these, the chemopreventive, anti-inflammatory and anti
      cancer effects are probably the most interesting. As xanthohumol is hardly
      soluble in water and able to undergo conversion to isoxanthohumol we determined
      several handling characteristics for cell culture work with this compound.
      Recovery experiments revealed that working with xanthohumol under cell culture
      conditions requires a minimal amount of 10% FCS to increase its solubility to
      reasonable concentrations (-50-75 micromol/l) for pharmacological in vitro tests.
      Additionally, more than 50% of xanthohumol can be absorbed to various plastic
      materials routinely used in the cell culture using FCS concentrations below 10%.
      In contrast, experiments using fluorescence microscopy in living cells revealed
      that detection of cellular intake of xanthohumol is hampered by concentrations
      above 1% FCS.

PMID- 22393839
TI  - Quality control of cytotoxic drug preparations by means of Raman spectroscopy.

PMID- 22393840
TI  - [New guidelines for veterinary antibiotic use].

PMID- 22393841
TI  - [Lose stitches].

PMID- 22393842
TI  - [Professional development project veterinary leadership].

PMID- 22393843
TI  - [Trends from the GD monitoring].

PMID- 22393844
TI  - Epizootic of ovine congenital malformations associated with Schmallenberg virus
      infection.
AB  - Epizootic outbreaks of congenital malformations in sheep are rare and have, to
      the best of our knowledge, never been reported before in Europe. This paper
      describes relevant preliminary findings from the first epizootic outbreak of
      ovine congenital malformations in the Netherlands. Between 25 November and 20
      December 2011, congenital malformations in newborn lambs on sheep farms
      throughout the country were reported to the Animal Health Service in Deventer.
      Subsequently, small ruminant veterinary specialists visited these farms and
      collected relevant information from farmers by means of questionnaires. The
      deformities varied from mild to severe, and ewes were reported to have given
      birth to both normal and deformed lambs; both male and female lambs were
      affected. Most of the affected lambs were delivered at term. Besides malformed
      and normal lambs, dummy lambs, unable to suckle, were born also on these farms.
      None of the ewes had shown clinical signs during gestation or at parturition.
      Dystocia was common, because of the lambs' deformities. Lambs were submitted for
      post-mortem examination, and samples of brain tissue were collected for virus
      detection. The main macroscopic findings included arthrogryposis, torticollis,
      scoliosis and kyphosis, brachygnathia inferior, and mild-to-marked hypoplasia of
      the cerebrum, cerebellum and spinal cord. Preliminary data from the first ten
      affected farms suggest that nutritional deficiencies, intoxication, and genetic
      factors are not likely to have caused the malformations. Preliminary diagnostic
      analyses of precolostral serum samples excluded border disease virus, bovine
      viral diarrhoea virus, and bluetongue virus. In December 2011, samples of brain
      tissue from 54 lambs were sent to the Central Veterinary Institute of Wageningen
      University Research, Lelystad. Real-time PCR detected the presence of a virus,
      provisionally named the Schmallenberg virus, in brain tissue from 22 of the 54
      lambs, which originated from seven of eight farms that had submitted lambs for
      post-mortem examination. This Schmallenberg virus was first reported in Germany
      and seems to be related to the Shamonda, Aino, and Akabane viruses, all of which
      belong to the Simbu serogroup of the genus Orthobunyavirus of the family
      Bunyaviridae. These preliminary findings suggest that the Schmallenberg virus is
      the most likely cause of this epizootic of ovine congenital malformations, which
      is the first such outbreak reported in Europe.

PMID- 22393845
TI  - [Diarrhea and loss of production on Dutch dairy farms caused by the Schmallenberg
      virus].
AB  - At the end of August and the first two weeks of September 2011 dozens of
      veterinary practitioners reported to GD Veekijker (Animal Health Service) several
      dairy herds with cows with sudden decreased milk production, watery diarrhea and
      sometimes fever. In the beginning these reports came from the Eastern region of
      the Netherlands, after that also from the other three regions. The percentages of
      diseased herds per veterinary practice varied from a few till dozens per cent.
      Extensive bacteriological, virological and parasitological testing of the feces
      of sick cows did not reveal an infectious cause of the clinical problems.
      Recently, 50 stored blood samples of clinically diseased cattle were tested for
      the Schmallenbergvirus using a PCR, and 36% (18/50) tested positive. A large
      group of control cows (n=115) was also tested with the PCR and all cattle tested
      negative. Likely the Schmallenbergvirus was the primary cause of the clinical
      symptoms in the Dutch dairy herds. Further research will be done to confirm this.

PMID- 22393846
TI  - [Nitrite poisoning in pigs through wastewater from air washers].

PMID- 22393847
TI  - [Cell count is also in goats useful].

PMID- 22393848
TI  - [Veterinary practice management ten years on the map].

PMID- 22393849
TI  - [Alumni structurally involved in veterinary education].

PMID- 22393850
TI  - [Veterinarian is no longer allowed to practice due to fraud with blood samples].

PMID- 22393851
TI  - [The cow as guru].

PMID- 22393852
TI  - PCT abolition: Ministers must slow down to avoid another Mid staffs.

PMID- 22393853
TI  - 'No clarity' over future of thousands of jobs.

PMID- 22393854
TI  - Dealing with variation.

PMID- 22393855
TI  - Small guy versus a stacked deck.

PMID- 22393856
TI  - Liberating ideas: The future is in their hands.

PMID- 22393857
TI  - Access: The call we've all being waiting for.

PMID- 22393858
TI  - Regulation: The complexity of competition rules creates confusion and risk.

PMID- 22393859
TI  - Competitive tendering 'as important' as AQP.

PMID- 22393860
TI  - Forty-one commissioning support services are proposed.

PMID- 22393861
TI  - Are we safe from another outbreak?

PMID- 22393862
TI  - Stop inflating CCGs before they pop.

PMID- 22393863
TI  - In sickness and in work.

PMID- 22393864
TI  - Enter the dragon.

PMID- 22393865
TI  - Service redesign: Joint benefits of streamlined care.

PMID- 22393866
TI  - Change management: talking about a revolution.

PMID- 22393867
TI  - Commissioning: A problem shared.

PMID- 22393868
TI  - To drive creativity, add some conformity.

PMID- 22393869
TI  - Hard-to-read fonts promote better recall.

PMID- 22393870
TI  - New project? Don't analyze--act.
AB  - In a predictable world, getting a new initiative off the ground typically
      involves analyzing the market, creating a forecast, and writing a business plan.
      But what about in an unpredictable environment? The authors recommend looking to
      those who are experts in navigating extreme uncertainty while minimizing risk:
      serial entrepreneurs. These business leaders act, learn, and build their way into
      the future. Managers in traditional organizations can do the same, starting with
      smart, low-risk steps that follow simple rules: Use the means at hand; stay
      within an acceptable loss; secure only the commitment needed for the next step;
      bring along only volunteers; link the initiative to a business imperative;
      produce early results; and manage expectations. Momentum is gained by continuing
      to act based on what is learned at each step. The launch of Clorox's Green Works
      product line is discussed as an example.

PMID- 22393872
TI  - Friends with benefits.

PMID- 22393871
TI  - When to make private news public.

PMID- 22393873
TI  - [Development of forensic thanatology through the prism of analysis of postmortem
      protocols collected at the Department of Forensic Medicine, Jagiellonian
      University].
AB  - When assessed based on the analysis of postmortem protocols, the successes of
      forensic thanatology appear to differ from those that might be assumed using as
      the foundation a review of publications and textbooks. The greatest achievements
      date back to as early as the 18th and 19th centuries, when the morphological
      changes observed in the majority of types of deaths resulting from disease
      associated and traumatic causes were described. Within the past 130 years,
      however, or in other words, in the period when autopsy protocols were written
      that are today collected in the archives of the Krakow Department of Forensic
      Medicine, the causes and mechanisms of death became understood even when the said
      factors were associated with discrete postmortem changes only or no no such
      changes whatsoever were left. At the end of the 19th century and for a long time
      afterwards, a difficult problem was posed by sudden deaths, where the postmortem
      examinations demonstrated solely atherosclerosis and the cause of death was
      described as "heart palsy". As it turned out, a great portion of such deaths
      represented individuals with myocardial infarction; in spite of its evident
      macroscopic presentation, the diagnostic management of the disease was
      progressing very slowly. Myocardial infarction, known at least since 1912, was
      associated by forensic medicine with the phenomenon of sudden death only in the
      forties, and the ability to detect myocardial infarction in practice developed
      only in the fifties of the last century. The achievement of the present
      dissertation is the formulation of a theory ascribing such a long delay in
      macroscopic diagnostics of myocardial infarction to forensic medicine specialists
      being attached to and fond of employing the "in situ" autopsy technique, which
      was unfavorable from the viewpoint of heart examination, since the organ was not
      dissected free and removed from the body in the course of a postmortem
      examination. When autopsies started to concentrate on hearts dissected free from
      large vessels, within several years, the number of diagnosed myocardial
      infarctions increased several times, what gave rise to a theory of a myocardial
      infarction epidemics formulated in some centers. A proof supporting the theory
      postulated by the author is a sudden increase in the number of deaths resulting
      from pulmonary embolism observed in the same several-year period; this diagnosis
      was also not facilitated by the "in situ" autopsy technique. Another cause of
      death, which - although undoubtedly common - was for years interpreted as "heart
      palsy" was alcohol poisoning. Evolution of methods used in chemical examinations
      for the presence of alcohol, and especially the use of blood tests rather than
      gastric contents tests allowed in time for determining alcohol poisoning as the
      cause of death and demonstrated the true extent of the phenomenon. Here, a
      milestone was the introduction of the Widmark method, what in turn resulted in
      changes in the toxicology theory, such as for example the use of a new term of
      "lethal concentration" in addition to the formerly employed notion of a "lethal
      dose", which is useless in the case of alcohol. Of lesser importance with respect
      to the number of cases, but of much greater significance in view of its
      association with homicides were the achievements in diagnostic management of
      strangulation. Choking and strangulation, as well as hanging--in spite of the
      fact that their fundamental features were known as early as in the 19th century-
      were really understood and the ability to diagnose these phenomena was achieved
      only in the interwar period. Such a long delay resulted from the autopsy
      technique that did not include examination of the organs situated in the neck, as
      well as from difficulties in acquiring experience in examining the type of
      homicide that was very uncommon. On the other hand, for many years, the erroneous
      theory of the fluidity of blood in a corpse as an indicator of violent
      strangulation resulted in dubious opinions on strangling by blocking the
      respiratory orifices of the victim, especially in cases of infanticides. Another
      erroneous theory, which was obligatory in forensic thanatology, was the theory of
      thymolymphatic state, which used thymic hypertrophy to explain deaths of young
      individuals resulting from a small injury or even strong emotion. Statistical
      tests and development of general medicine allowed for disproving the theory. In
      the diagnostics management of death from hypothermia, despite the fact that its
      most important features--Wischnewski spots and the loss of liver glycogen--had
      been known for a long time, they were regarded useless for several score years.
      At this time, cases of death from hypothermia were included into the category of
      "heart palsy". Despite several changes of the authorities, a review of autopsy
      protocols prepared in the Krakow Department of Forensic Medicine provided the
      author with a wealth of information of significant historical value. Protocols
      dating back to the period of Nazi occupation allowed for documenting and
      analyzing the types of torture employed by the Gestapo, but also for discovering
      a surprisingly large number of postmortem examinations of bodies of occupation
      functionaries who were sentenced to death by the Polish Underground State. After
      World War II, the Department examined numerous victims originating from both
      sides of skirmishes fought at the time by the then authorities and the armed
      underground movement, or even individuals murdered in the course of
      interrogations. The archives of autopsy protocols became a valuable source
      helpful in estimating the number of victims of the Soviet Army that was stationed
      in Poland, and later provided the only supply of information needed for
      evaluation of the number of fatal accidents among the builders of the Krakow
      district of Nowa Huta. Based on the autopsy protocols it may be concluded that
      the number of victims of anti-Jewish riots that sparked off in Krakow soon after
      World War II was over, was most likely lower than that assessed by the
      historians; on the other hand, the number of victims of similar riots occurring
      after World War I was higher than the historians believed. A great span of time
      over which the protocols were written allowed for following some socioeconomic
      changes. In the period before Poland's regaining independence, a significant
      social problem was posed by deaths of infants entrusted to foster care to "angel
      makers" After independence was regained, a similar problem emerged, consisting of
      deaths of young females due to complications of illegal abortions. In the post
      war period, such a social problem was found in deaths due to fatal alcohol
      poisoning; the annual number of such cases increased almost tenfold within the
      past 50 years. In addition to obvious cases associated with the war, the Nazi
      occupation was characterized by a sudden, manifold increase in the number of
      methanol poisonings and an unexpectedly high increase in the number of victims of
      fatal traffic road accidents, especially those involving trains and streetcars.
      Over the past 130 years, there were significant changes in the selection of
      poisons used for suicidal purposes. In the beginning of the analyzed period,
      suicides were committed by ingesting caustic substances that damaged
      parenchymatous organs--these poisons were very brutal in their action, but easy
      to detect. As new pharmaceuticals--central nervous system depressants--were being
      introduced to therapeutic management, they gradually replaced caustic and
      parenchymatous poisons. In contrast to the early phase of the analyzed period,
      poisoning with such medications cannot be detected on autopsy, yet their
      introduction promoted the development of forensic toxicology. Nevertheless, for
      several score years, the heaviest toll was taken by carbon monoxide from the
      municipal gasworks, which appeared in 1905 and disappeared in 1982, killing as
      many as in excess of 50 individuals per year. In the collection of more than 60
      thousand autopsy protocols, the author managed to find hitherto unknown,
      interesting cases, e.g. that describing a victim of a fatal accident in a stone
      quarry, witnessed by Karol Wojtyla during WWII, a victim of an unknown
      assassination attempt on the life of Boleslaw Bierut, as well as protocols of
      postmortem examinations of bodies of the People's Republic of Poland intelligence
      agents who died while posted abroad.

PMID- 22393874
TI  - Public participation in soil surveys: lessons from a pilot study in England.
AB  - In many countries there are policies in place that impact on soils, but very few
      legislative or policy tools specifically for the protection of soil. Recent EU
      legislative proposals on soil protection have been met with opposition on the
      grounds of excessive cost and resource demands. With the need for evidence based
      policy, and recognition that involving the public in environmental monitoring is
      an effective way of increasing understanding and commitment, there has been
      growing interest in soil surveys. In addition, it is accepted that the success of
      environmental policies depends greatly on how effectively scientists, regulators,
      stakeholders, and society communicate. This paper presents the Open Air
      Laboratories (OPAL) Soil and Earthworm Survey as an example of public
      participation in soil surveys that aims to integrate the above. It is
      demonstrated how such surveys generate data that can be used to prioritise soil
      assessment, in order to address some of the concerns and objections to soil
      protection policies. Lessons from this pilot study in England highlight that with
      strategic planning of civic participation activities, this approach can deliver
      improvements in the quality of the evidence collected and allow for effective
      public involvement in policymaking and implementation, on top of direct
      educational benefits.

PMID- 22393876
TI  - Solid-state NMR crystallography through paramagnetic restraints.
AB  - Pseudocontact shifts (PCSs) measured by solid-state NMR spectroscopy (SS-NMR) on
      microcrystalline powders of a paramagnetic metalloprotein permit NMR
      crystallography. Along with other restraints for SS-NMR experiments, the protein
      molecular structure as well as the correct crystal packing are obtained.

PMID- 22393875
TI  - A unique role of dynein and nud family proteins in corticogenesis.
AB  - Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a
      human neuronal migration defect, and DCX mutations are the most common cause of X
      linked lissencephaly. Lissencephaly is characterized by a smooth cerebral
      surface, thick cortex and dilated lateral ventricles associated with mental
      retardation and seizures due to defective neuronal migration. Lissencephaly due
      to the heterozygous loss of the gene LIS1 is a good example of a
      haploinsufficiency disorder. LIS1 was deleted or mutated in a large proportion of
      patients with lissencephaly in a heterozygous fashion. A series of studies
      discovered that LIS1 is an essential regulator of cytoplasmic dynein. Notably,
      the role of LIS1 in regulating dynein activity is highly conserved among
      eukaryotes. In particular, we reported that LIS1 and NDEL1 are essential for
      dynein transport to the plus-end of microtubules by kinesin, which is essential
      to maintain the proper distribution of cytoplasmic dynein within the cell. In
      addition, we report that mNUDC (mammalian NUDC) interacts with kinesin-1 and is
      required for the anterograde transport of a cytoplasmic dynein complex by kinesin
      1. A microtubule organization and motor proteins are further modulated by post
      translational modifications, including phosphorylation and palmitoylation. These
      modifications share a common pathway with mitotic cell division. For example,
      Aurora-A is activated during neurite elongation, and phosphorylates NDEL1, which
      facilitates microtubule extension into neurite processes. Elucidations of
      molecular pathways involving neuronal migrations provide us a chance to design a
      novel strategy for neurological disorder due to defective neuronal migration. For
      example, inhibition of calpain protects LIS1 from proteolysis resulting in the
      augmentation of LIS1 levels, which leads to rescue of the phenotypes that are
      observed in Lis1+/- mice. Endeavoring to address the regulation of the
      microtubule network and motor proteins will help in understanding not only
      corticogenesis but neurodegenerative disorders.

PMID- 22393877
TI  - Estrogen inhibits apoptosis and promotes CC motif chemokine ligand 13 expression
      on synovial fibroblasts in rheumatoid arthritis.
AB  - OBJECTIVE: Female patients have a higher prevalence of rheumatoid arthritis (RA)
      than male patients, suggesting that female sex hormones contribute to the disease
      pathogenesis. We herein report the findings of our study, which was conducted to
      clarify the role of estrogen in the pathogenesis of RA. METHODS: Cultured human
      synovial fibroblasts from a patient with RA were treated with 17beta-estradiol
      (E(2)). The effects of E(2) against cellular activation and apoptosis were
      evaluated. To identify the disease-related genes altered by E(2) treatment, the
      changes in the gene expression of the cells stimulated with and without E(2) were
      evaluated using a microarray analysis. RESULTS: We found that E(2)-mediated
      cellular activation signaling through extracellular signal-regulated kinase (ERK)
      1/2. E(2) possessed a suppressive effect for apoptosis and a promotive effect for
      tumor necrosis factor (TNF)-alpha-induced matrix metalloproteinase (MMP)-3
      production on the synovial fibroblasts. A microarray analysis revealed that E(2)
      profoundly upregulated CC motif chemokine ligand 13 (CCL13) gene expression.
      CONCLUSIONS: E(2) could mediate cellular activation signaling through ERK-1/2 on
      the synovial fibroblasts. The present data suggest that E(2) has adverse effects
      on the pathogenesis of RA as a result of unregulated cell death, increased TNF
      alpha-induced MMP-3 production, and CCL13 overproduction, subsequently resulting
      in the disease progression of RA.

PMID- 22393878
TI  - Interactions of engineered nanomaterials in physiological media and implications
      for in vitro dosimetry.
AB  - In vitro toxicity assays are efficient and inexpensive tools for screening the
      increasing number of engineered nanomaterials (ENMs) entering the consumer
      market. However, the data produced by in vitro studies often vary substantially
      among different studies and from in vivo data. In part, these discrepancies may
      be attributable to lack of standardisation in dispersion protocols and inadequate
      characterisation of particle-media interactions which may affect the particle
      kinetics and the dose delivered to cells. In this study, a novel approach for
      preparation of monodisperse, stabilised liquid suspensions is presented and
      coupled with a numerical model which estimates delivered dose values. Empirically
      derived material- and media-specific functions are presented for each media-ENM
      system that can be used to convert administered doses to delivered doses. The
      interactions of ENMs with a variety of physiologic media were investigated and
      the importance of this approach was demonstrated by in vitro cytotoxicity assays
      using THP-1 macrophages.

PMID- 22393879
TI  - Formulation development of physiological environment responsive periodontal drug
      delivery system for local delviery of metronidazole benzoate.
AB  - The objective of the present investigation was to develop and evaluate
      physiological environment responsive periodontal drug delivery system (PERPDDS)
      for local delivery of metronidazole benzoate. Poly-epsilon-caprolactone an in
      situ precipitating polymer was used in combination with, carbopol 934P, a pH
      simulative polymer to develop PERPDDS. The prepared PERPDDS was evaluated for
      various parameters such as in vitro gelling capacity, viscosity, rheology,
      compatibility study, and in vitro diffusion study. A 3(2) full factorial design
      was used to investigate the influence of formulation variables. Drug release data
      from all formulations were fitted to different kinetic models and the korsemeyer
      peppas model was found the best fit model. The value of diffusional exponent (n)
      was in between 0.3283 and 0.3979 indicating purely fickian diffusion release
      mechanism. Increasing the concentration of each polymeric component increases
      viscosity, and time for 50% and 90% drug release was observed and graphically
      represented by the surface response and contour plots.

PMID- 22393880
TI  - Ultrasensitive chemical detection using a nanocoax sensor.
AB  - We report on the design, fabrication, and performance of a nanoporous, coaxial
      array capacitive detector for highly sensitive chemical detection. Composed of an
      array of vertically aligned nanoscale coaxial electrodes constructed with porous
      dielectric coax annuli around carbon nanotube cores, this sensor is shown to
      achieve parts per billion level detection sensitivity, at room temperature, to a
      broad class of organic molecules. The nanoscale, 3D architecture and microscale
      array pitch of the sensor enable rapid access of target molecules and chip-based
      multiplexing capabilities, respectively.

PMID- 22393881
TI  - Sex-specific association of age with carotid artery distensibility: multi-ethnic
      study of atherosclerosis.
AB  - BACKGROUND: Older women have a higher prevalence of systolic hypertension than do
      men; however, whether or not this relates to arterial properties, such as
      distensibility coefficient (DC), is not known. We examined whether the
      association of carotid artery DC with age differed by sex in the Multi-Ethnic
      Study of Atherosclerosis (MESA). METHODS: B-mode ultrasound-measured carotid
      diameters and brachial pressures were obtained from 6359 participants (53%
      female, 38% white, 12% Chinese, 27% black, 22% Hispanic, aged 45-85 years) of the
      MESA baseline examination. The within-individual slopes of 2log(diameter) vs.
      blood pressure fit using mixed models (MM) are interpreted as the DC, and
      interaction terms are interpreted as differences in DC. The MM calculation allows
      for correction of the confounding caused by the association of age, sex, and race
      with blood pressure, the denominator in the calculation of DC. RESULTS: DC was
      associated with age, sex, and race (all p<0.001). Women had a greater age-related
      lowering of DC compared to men (2.52*10(-5) vs. 2.16*10(-5)/mm Hg lower DC per
      year of age, p=0.006). Mean diameter of carotid arteries was greater with age
      (p<0.001); this association also was significantly stronger in women compared to
      men (0.24% vs. 0.14% larger mean carotid diameter per year of age, p<0.001).
      CONCLUSIONS: Greater stiffening and enlargement of arteries are seen in older
      women compared to older men. This implies that the afterload on the heart of
      older women is likely to be greater than that among older men.

PMID- 22393883
TI  - Falls in old age: a threat to identity.
AB  - AIM AND OBJECTIVE: This study aimed to understand older people's perceptions of
      their and other older peoples' falls risk, to increase understanding of why older
      people might not believe falls are relevant to themselves. BACKGROUND: One-third
      of the people aged>=65 years (older people) fall yearly. Many older people do not
      participate in falls prevention programmes because they purport they are not
      personally vulnerable. DESIGN: A qualitative study was conducted, guided by the
      tenets of grounded theory. METHOD: Semi-structured interviews were conducted with
      nine community-dwelling older people living in metropolitan Adelaide, South
      Australia. The interview explored participant's direct and indirect experience of
      falling, their perceived chance of falling in the next 12 months and that of
      others of the same age and sex to themselves and their reasons for this. RESULTS:
      Participants carefully presented themselves as being 'not the type who fall', who
      they view negatively. They believed their or their friends past or future falls
      were (or could be) because of factors outside of their personal control or
      because they were not paying attention at that moment of falling, as opposed to
      being the type of person who falls. They used these explanations as strategies to
      maintain or protect their identity as being physically competent. CONCLUSIONS:
      Older people know that falling can be viewed negatively. Falling is a threat to
      their identity as the type of person who does not fall. This explanation is
      consistent with self-presentation theory, where people use accounting strategies
      in social interaction to create a desired impression. RELEVANCE TO CLINICAL
      PRACTICE: Falls prevention messages are likely to be rejected if the target group
      associate the message with a negative identity. These findings can assist nurses
      to understand older people's reluctance to engage in falls prevention and can
      stimulate thinking regarding alternative engagement strategies.

PMID- 22393882
TI  - Factors affecting the methanol content and yield of plum brandy.
AB  - This study was conducted to determine the influence of plum cultivar, harvest
      year, and plum component on the methanol content and the yield of plum brandy.
      Seven plum cultivars (Geneva Mirabelle, French Damson, Pozegaca, Oblinaya, Early
      Golden, Lohr, and Rosy Gage) grown in the Finger Lakes fruit region of New York
      State were processed into mash and juice. The samples of plum mash or juice were
      fermented with commercial Red Star wine yeast Montrachet (Sachharomyces
      cerevisiae Davis 522) for 12 d. The fermented samples were distilled, and the
      distillates were analyzed for methanol, ethanol, and higher alcohols by high
      performance liquid chromatography. Duncan's multiple range tests show significant
      differences in the methanol content and the yield of plum brandy made from 7 plum
      cultivars. The harvest year also had a significant effect on the methanol content
      and the yield of plum brandy. Student's t-test results indicate that plum juices
      gave a lower methanol content of brandy than plum mashes without significantly
      reducing the brandy yield. The results of the current research can be used by the
      industry to select the better plum cultivar and to adopt the process to improve
      the product yield and quality. PRACTICAL APPLICATION: The brandy industry can
      apply the results of the current research to improve product yield and to reduce
      the methanol content of plum brandy. The economic benefits to the brandy
      producers adopting the brandy production process will be significant due to the
      sales of new products with an acceptable level of methanol.

PMID- 22393884
TI  - Could antivirals be used to treat Alzheimer's disease?

PMID- 22393886
TI  - Challenges in assessing associations between hormonal contraceptive use and the
      risks of HIV-1 acquisition and transmission.
AB  - Prior observational studies produced inconsistent findings regarding hormonal
      contraception (HC) and risks of HIV acquisition and transmission. Heffron et al.
      conducted secondary data analyses on 3790 HIV discordant couples enrolled in two
      studies (a randomized trial of HSV-2 suppression and a study of immune correlates
      of HIV-1 protection) to assess HIV-1 acquisition and transmission in relation to
      HC use in females. HIV incidence among female HC nonusers was 3.8/100 person
      years (py), compared to 6.9/100 py among injectable users (p = 0.04) and 5.9/100
      py in oral contraceptive users (p = 0.33). Among men, HIV incidence was 1.5/100
      py in partners of HIV-positive HC nonusers, compared to 2.6/100 py in partners of
      injectable users (p < 0.05) and 2.5/100 py in men whose HIV-infected partners
      used oral contraceptives (p = 0.31). Study strengths included frequent follow up,
      excellent retention, known HIV exposure and viral load in the index infected
      partner, genetic linkage of virus from both partners and sexual behavior
      information. However, confounding by factors that cannot be controlled, including
      misreporting of condom use, is likely, given participants' high pregnancy rates.
      Clinicians and clients need to balance potential HC risks with the known risks of
      unwanted pregnancies. Condom use remains essential for HIV prevention regardless
      of other contraceptive usage.

PMID- 22393887
TI  - Research trends on pathogenic Cryptococcus species in the last 20 years: a global
      analysis with focus on Brazil.
AB  - AIMS: Recent data demonstrates that cryptococcosis caused by Cryptococcus
      neoformans or Cryptococcus gattii kills approximately 600,000 people per year in
      the world. In Brazil, cryptococcosis has recently been identified as the most
      fatal mycosis in AIDS patients. In this study, we aimed to map research into C.
      neoformans and C. gattii in the world, with a focus on the Brazilian contribution
      to this area. METHODS: The parameters used for this analysis were based on
      publication records, including number of articles published, citation indices,
      journal impact factor and distribution of authorship in the last two decades.
      RESULTS: Our global analysis of publications demonstrated that, in the last 20
      years, the USA was the country that produced the highest number of scientific
      articles in the Cryptococcus field, while Brazil occupied the third position.
      Brazilian productivity, however, showed a steady tendency to increase, in
      contrast to the USA and other countries. The average impact factor of journals at
      which articles authored by Brazilians were published was 2.58, which represented
      approximately half the value found for papers of American authorship. Studies
      authored by Brazilian scientists showed relatively low averages of citations per
      article, in comparison to papers published by researchers from the USA, France,
      Australia, The Netherlands and Germany, among others. CONCLUSION: This study
      demonstrates that the contribution of Brazilian scientists to the Cryptococcus
      field is continually growing, although papers produced in Brazil apparently have
      poor repercussion in comparison to those generated in developed countries.

PMID- 22393888
TI  - Hepatitis A virus evolution and the potential emergence of new variants escaping
      the presently available vaccines.
AB  - Hepatitis A is the most common infection of the liver worldwide and is fecal
      orally transmitted. Its incidence tends to decrease with improvements in hygiene
      conditions but at the same time its severity increases. Hepatitis A virus is the
      causative agent of acute hepatitis in humans and belongs to the Hepatovirus genus
      in the Picornaviridae family, and it has very unique characteristics. This
      article reviews some molecular and biological properties that allow the virus to
      live in a very quiescent way and to build an extremely stable capsid that is able
      to persist in and out of the body. Additionally, the relationship between the
      genomic composition and the structural and antigenic properties of the capsid is
      discussed, and the potential emergence of antigenic variants is evaluated from an
      evolutionary perspective.

PMID- 22393890
TI  - Post-translational modifications of host proteins by Legionella pneumophila: a
      sophisticated survival strategy.
AB  - Eukaryotic proteins are tightly regulated by post-translational modifications,
      leading to a very subtle degree of regulation in time and space. Pathogen
      mediated post-translational modifications are key strategies to modulate host
      factors by targeting central signaling pathways in the host cell. Legionella
      pneumophila, an intracellular pathogen that coevolved with protozoan hosts,
      encodes a large arsenal of secreted effectors conferring the ability to evade
      host cellular defenses and to manipulate them to promote invasion and
      intracellular replication. Conservation of many signaling pathways of protozoa in
      human macrophages confers the ability of L. pneumophila to infect humans, causing
      a severe pneumonia called legionnaires' disease. Most of the secreted proteins
      are delivered by the Dot/Icm type IV secretion system and several of these have
      been shown to act on different cellular pathways critical for infection.
      Moreover, multiple effectors target a single host function to orchestrate
      bacterial survival. In this review, we focus on those effectors in the repertoire
      of L. pneumophila proteins that target key cellular pathways by specific post
      translational modifications.

PMID- 22393889
TI  - Oncolytic Newcastle disease virus for cancer therapy: old challenges and new
      directions.
AB  - Newcastle disease virus (NDV) is an avian paramyxovirus, which has been
      demonstrated to possess significant oncolytic activity against mammalian cancers.
      This review summarizes the research leading to the elucidation of the mechanisms
      of NDV-mediated oncolysis, as well as the development of novel oncolytic agents
      through the use of genetic engineering. Clinical trials utilizing NDV strains and
      NDV-based autologous tumor cell vaccines will expand our knowledge of these novel
      anticancer strategies and will ultimately result in the successful use of the
      virus in the clinical setting.

PMID- 22393892
TI  - Molecular mechanisms of beta-lactam resistance in Streptococcus pneumoniae.
AB  - Alterations in the target enzymes for beta-lactam antibiotics, the penicillin
      binding proteins (PBPs), have been recognized as a major resistance mechanism in
      Streptococcus pneumoniae. Mutations in PBPs that confer a reduced affinity to
      beta-lactams have been identified in laboratory mutants and clinical isolates,
      and document an astounding variability of sites involved in this phenotype.
      Whereas point mutations are selected in the laboratory, clinical isolates display
      a mosaic structure of the affected PBP genes, the result of interspecies gene
      transfer and recombination events. Depending on the selective beta-lactam,
      different combinations of PBP genes and mutations within are involved in
      conferring resistance, and astoundingly in non-PBP genes as well.

PMID- 22393893
TI  - Polyphosphate kinase 1 is required for the pathogenesis process of meningitic
      Escherichia coli K1 (RS218).
AB  - AIM: Polyphosphate kinase 1 (PPK1), encoded by the ppk1 gene, is one of the major
      enzymes to reversibly catalyze the synthesis of polyphosphate (poly P) from the
      terminal phosphate of ATP. Poly P confers resistance to stress in a number of
      bacterial species but its role in the virulence of meningitic bacterial pathogens
      is unknown. The aim of this study was to determine the role of PPK1 in the
      pathogenesis of Escherichia coli meningitis. MATERIALS & METHODS: An isogenic in
      frame ppk1 deletion mutant (PD44) of E. coli K1 strain E44 was constructed and
      characterized. Human brain microvascular endothelial cells and neonatal rats were
      used as the in vitro and in vivo models, respectively, to evaluate bacterial
      adhesion/invasion and the abilities of bacteria crossing the blood-brain barrier
      (BBB) to cause meningitis. The survival of PD44 and E44 under osmotic and acid
      stress conditions were also examined. RESULTS: Poly P levels in E44 were clearly
      higher than those in PD44, especially at the stationary phase (SP). The ppk1
      deletion mutant PD44 also showed poor survival rates during osmotic shock and
      acidic challenge, which the bacteria would face during pathogenesis. In vitro and
      in vivo assays revealed that PD44 was defective in bacterial adhesion and
      translocation across the BBB. By using the Evans blue method, we found that E44
      induced permeability of the BBB in neonatal rats was significantly higher than
      that of the animals infected with PD44. Cytokine ELISA results showed that the
      TNF-alpha and IL-1beta levels in the serum and brain tissues of the neonatal rats
      infected with PD44 were lower than that of the E44 group. A more obvious
      meningeal inflammation could be observed in the brain tissues of the rats
      infected with E44 when compared with that of the PD44 group by histopathological
      examination. Furthermore, the mRNA expression of IbeR, which is an RpoS-like
      regulator contributing to the SP regulation in E44, was found to be decreased in
      PD44 when compared with the parent strain. PD44 was also deficient in mRNA
      expression of the invasin IbeA, the adhesin FimH and the outer member protein A,
      which contributes to E44 penetration across BBB and resistance to the
      stimulations of low pH and high osmolarity. CONCLUSION: These results indicate
      that ppk1 plays an important role in stress adaption and virulence in meningitic
      E. coli K1 strain E44, and controls the relevant phenotypes by modulating the
      expression of the SP regulatory gene ibeR and the virulence genes ibeA, fimH and
      ompA.

PMID- 22393895
TI  - Effect of organic and conventional cropping systems on ascorbic acid, vitamin C,
      flavonoids, nitrate, and oxalate in 27 varieties of spinach (Spinacia oleracea
      L.).
AB  - This study was undertaken to compare the levels of ascorbic acid, vitamin C,
      flavonoids, nitrate, and oxalate in 27 spinach varieties grown in certified
      organic and conventional cropping systems. Liquid chromatography-electrospray
      ionization-tandem mass spectrometry (LC-(ESI)MS/MS) of methanolic extracts of
      spinach demonstrated 17 flavonoids, including glucuronides and acylated di- and
      triglycosides of methylated and methylenedioxyderivatives of 6-oxygenated
      flavonoids. The mean levels of ascorbic acid and flavonoids were significantly (p
      < 0.001) higher in the organically grown [40.48 +/- 6.16 and 2.83 +/- 0.03 mg/kg
      of fresh weight (FW)] spinach compared to the conventionally grown spinach (25.75
      +/- 6.12 and 2.27 +/- 0.02 mg/kg of FW). Conversely, the mean levels of nitrate
      were significantly (p < 0.001) higher in the conventionally grown spinach
      compared to the organically grown spinach. No significant effects were observed
      in the oxalate content of spinach from either production system. The levels of
      nitrate correlated negatively with those of ascorbic acid, vitamin C, and total
      flavonoids and showed a positive correlation with the oxalate content. These
      results suggest that organic cropping systems result in spinach with lower levels
      of nitrates and higher levels of flavonoids and ascorbic acid.

PMID- 22393891
TI  - Defense at the border: the blood-brain barrier versus bacterial foreigners.
AB  - Bacterial meningitis is among the top ten causes of infectious disease-related
      deaths worldwide, with up to half of the survivors left with permanent
      neurological sequelae. The blood-brain barrier (BBB), composed mainly of
      specialized brain microvascular endothelial cells, maintains biochemical
      homeostasis in the CNS by regulating the passage of nutrients, molecules and
      cells from the blood to the brain. Despite its highly restrictive nature, certain
      bacterial pathogens are able to gain entry into the CNS resulting in serious
      disease. In recent years, important advances have been made in understanding the
      molecular and cellular events that are involved in the development of bacterial
      meningitis. In this review, we summarize the progress made in elucidating the
      molecular mechanisms of bacterial BBB-crossing, highlighting common themes of
      host-pathogen interaction, and the potential role of the BBB in innate defense
      during infection.

PMID- 22393896
TI  - Prevalence of Ancylostoma braziliense in cats in three northern counties of
      Florida, United States.
AB  - A convenience sampling of fecal specimens from 40 cats in northern Florida was
      examined for the presence of Ancylostoma braziliense eggs by using centrifugal
      sugar flotation and polymerase chain reaction (PCR)-restriction fragment length
      polymorphism (RFLP). Of the 40 samples, 26 (65%) contained hookworm eggs. DNA
      from 24 samples was successfully amplified using PCR; using RFLP, 10 samples were
      identified as containing DNA of A. braziliense (41.7% of the 24 samples that
      successfully amplified). Of these, 6 samples contained DNA of both Ancylostoma
      tubaeforme and A. braziliense, and 4 samples contained only DNA of A.
      braziliense. The remaining samples (n  =  14) contained only the DNA of A.
      tubaeforme, except for 1 sample that had no discernible bands after RFLP.

PMID- 22393897
TI  - Activation of aerobic metabolism by Amaranth oil improves heart rate variability
      both in athletes and patients with type 2 diabetes mellitus.
AB  - The aim of present research was to study the effects of Amaranth oil (AmO)
      supplementation on aerobic metabolism and heart rate variability (HRV) in type 2
      diabetes mellitus patients and in athletes. Several parameters of aerobic
      metabolism and HRV were assessed. Supplementation with AmO caused mild pro
      oxidant activity resulting in improved uptake of oxidative destruction products
      and modulation of catalase and SOD activity with subsequent development of an
      antioxidant effect. These findings were very distinct in athletes but less
      pronounced in diabetics. Redistribution of haemoglobin ligands in athletes
      indicates involvement of haemoproteins in free radical reactions during AmO
      supplementation. Improvement in HRV by daily consumption of AmO as observed in
      both study groups suggested increased production of endogenous oxygen and
      enhancement of the cardio-respiratory function. The advantage of activation of
      aerobic metabolism in OS-related disorders resulting in improved self
      organization of the living system and hormetic reaction mechanisms are discussed.

PMID- 22393898
TI  - Effects of bilastine on T-wave morphology and the QTc interval: a randomized,
      double-blind, placebo-controlled, thorough QTc study.
AB  - BACKGROUND AND OBJECTIVES: The International Conference of Harmonisation (ICH)
      E14 guideline for thorough QT studies requires assessing the propensity of new
      non-antiarrhythmic drugs to affect cardiac repolarization. The present study
      investigates whether a composite ECG measure of T-wave morphology (Morphology
      Combination Score [MCS]) can be used together with the heart rate corrected QT
      interval (QTc) in a fully ICH E14-compliant thorough QT study to exclude
      clinically relevant repolarization effects of bilastine, a novel antihistamine.
      METHODS: Thirty participants in this crossover study were randomly assigned to
      receive placebo, moxifloxacin 400 mg, bilastine at therapeutic and
      supratherapeutic doses (20 and 100 mg) and bilastine 20 mg co-administered with
      ketoconazole 400 mg. Resting ECGs recorded at 12 nominal time points before and
      after treatments were used to determine Fridericia corrected QTc (QTcF) and MCS
      from the T-wave characteristics: asymmetry, flatness and notching. RESULTS: There
      were no effects of bilastine monotherapy (20 and 100 mg) on MCS or QTcF at those
      study times where the bilastine plasma concentrations were highest. MCS changes
      for bilastine monotherapy did not exceed the normal intrasubject variance of T
      wave shapes for triplicate ECG recordings. Maximum QTcF prolongation for
      bilastine monotherapy was 5 ms or less: 3.8 ms (90% CI 0.3, 7.3 ms) for bilastine
      20 mg and 5.0 ms (90% CI 2.0, 8.0 ms) for bilastine 100 mg. There were no
      indications of bilastine inducing larger repolarization effects on T-wave
      morphology as compared with the QTcF interval, as evidenced by the similarity of
      z-score equivalents for placebo-corrected changes in MCS and QTcF values.
      CONCLUSION: This study shows that bilastine, at therapeutic and supratherapeutic
      dosages, does not induce any effects on T-wave morphology or QTcF. These results
      confirm the absence of an effect for bilastine on cardiac repolarization.

PMID- 22393899
TI  - Subthalamic nucleus stimulation restores the efferent cortical drive to muscle in
      parallel to functional motor improvement.
AB  - Pathological synchronization in large-scale motor networks constitutes a
      pathophysiological hallmark of Parkinson's disease (PD). Corticomuscular
      synchronization in PD is pronounced in lower frequency bands (< 10 Hz), whereas
      efficient cortical motor integration in healthy persons is driven in the beta
      frequency range. Electroencephalogram and electromyogram recordings at rest and
      during an isometric precision grip task were performed in four perioperative
      sessions in 10 patients with PD undergoing subthalamic nucleus deep-brain
      stimulation: (i) 1 day before (D0); (ii) 1 day after (D1); (iii) 8 days after
      implantation of macroelectrodes with stimulation off (D8StimOff); and (iv) on
      (D8StimOn). Analyses of coherence and phase delays were performed in order to
      challenge the effects of microlesion and stimulation on corticomuscular coherence
      (CMC). Additionally, local field potentials recorded from the subthalamic nucleus
      on D1 allowed comprehensive mapping of motor-related synchronization in
      subthalamocortical and cerebromuscular networks. Motor performance improved at
      D8StimOn compared with D0 and D8StimOff paralleled by a reduction of muscular
      activity and CMC in the theta band (3.9-7.8 Hz) and by an increase of CMC in the
      low-beta band (13.7-19.5 Hz). Efferent motor cortical drives to muscle presented
      mainly below 10 Hz on D8StimOff that were suppressed on D8StimOn and occurred on
      higher frequencies from 13 to 45 Hz. On D1, coherence of the high-beta band (20.5
      30.2 Hz) increased during movement compared with rest in subthalamomuscular and
      corticomuscular projections, whereas it was attenuated in subcorticocortical
      projections. The present findings lend further support to the concept of
      pathological network synchronization in PD that is beneficially modulated by
      stimulation.

PMID- 22393900
TI  - Activation of the extracellular signal-regulated kinase pathway contributes to
      the behavioral deficit of fragile x-syndrome.
AB  - Fragile X syndrome (FXS) is a developmental disorder caused by the loss of
      Fragile X Mental Retardation 1 (FMR1) gene function because of a CGG repeat
      expansion (> 200 repeats) in the gene. The molecular mechanism(s) linking loss of
      FMR1 function to the molecular pathology and cognitive/behavioral disability
      remain unclear. Given the critical role of extracellular signal-regulated kinase
      (ERK) in synaptic plasticity and neurodevelopment, a number of recent studies
      have investigated ERK phosphorylation under basal conditions or upon mGluR
      induction using neuronal and peripheral tissues from Fmr1 knockout mice and
      peripheral tissues from FXS patients. However, these reports have presented
      conflicting results. The current study is the first to focus on the levels of ERK
      phosphorylation in brain tissue from human FXS patients. In both human brain
      tissue and brain tissue from Fmr1 knockout mice there was significantly increased
      phosphorylation of MEK1/2 and ERK. Indeed, treating Fmr1 knockout mice with the
      MEK1/2 inhibitor SL327 abrogated audiogenic seizure activity, a feature of the
      Fmr1 knockout mice that replicates the symptom in patients with FXS. These
      findings suggest that activation of the ERK pathway results in some cardinal
      cognitive and clinical features in FXS patients and likely have profound
      translational implications.

PMID- 22393901
TI  - Plasmids foster diversification and adaptation of bacterial populations in soil.
AB  - It is increasingly being recognized that the transfer of conjugative plasmids
      across species boundaries plays a vital role in the adaptability of bacterial
      populations in soil. There are specific driving forces and constraints of plasmid
      transfer within bacterial communities in soils. Plasmid-mediated genetic
      variation allows bacteria to respond rapidly with adaptive responses to
      challenges such as irregular antibiotic or metal concentrations, or opportunities
      such as the utilization of xenobiotic compounds. Cultivation-independent
      detection and capture of plasmids from soil bacteria, and complete sequencing
      have provided new insights into the role and ecology of plasmids. Broad host
      range plasmids such as those belonging to IncP-1 transfer a wealth of accessory
      functions which are carried by similar plasmid backbones. Plasmids with a
      narrower host range can be more specifically adapted to particular species and
      often transfer genes which complement chromosomally encoded functions. Plasmids
      seem to be an ancient and successful strategy to ensure survival of a soil
      population in spatial and temporal heterogeneous conditions with various
      environmental stresses or opportunities that occur irregularly or as a novel
      challenge in soil.

PMID- 22393902
TI  - Sensations of gas and pain and their relationship with compliance during
      distension in human colon.
AB  - BACKGROUND: Colonic mechanosensory afferents 'in parallel' to circular muscle
      activate prevertebral ganglion reflexes; 'in series', afferents convey visceral
      sensation to the central nervous system; and pain receptors are activated with
      muscle distension. Our aim was to analyze the relationships of gas and pain
      sensations during graded distensions, and the association of sensations with
      colonic compliance in conscious humans. METHODS: The data were acquired in a
      prior study performed on 60 healthy volunteers (aged 18-75 years) under baseline
      conditions. Colonic compliance was measured in response to 4 mmHg stepwise
      balloon distensions to estimate pressure at half-maximum volume (Pr(50%)).
      Sensation ratings for gas and pain were averaged over distensions at 16, 24, 30
      and 36 mmHg above baseline operating pressure. Associations between mean gas and
      pain ratings, and colonic compliance were assessed with Pearson correlations. KEY
      RESULTS: Gas and pain sensations were significantly correlated at all levels of
      distension (all P < 0.001). Significant inverse correlations between Pr(50%) and
      sensations of gas and pain were observed, suggesting that lower compliance was
      associated with lower sensations. Up to 25% of the variance in sensation may be
      attributed to colonic compliance. CONCLUSIONS & INFERENCES: These data are
      consistent with the hypothesis that, if circumferential colonic receptors are
      stimulated by distension to mediate gas and pain in humans, they are, at least
      partly, arranged 'in parallel' to the muscle layer.

PMID- 22393903
TI  - A novel A20 (TNFAIP3) antibody (Ber-A20) can be used to detect unmutated A20 by
      immunohistology.
AB  - AIMS:   A20 (TNFAIP3) is a nuclear factor-kappaB (NF-kappaB)-inducible component
      of tumour necrosis factor and Toll-like receptor intracellular signal
      transduction. It negatively regulates NF-kappaB, and has been identified as a
      tumour suppressor. Several studies have described A20 inactivation by deletion of
      the A20 locus at 6q23, inactivating mutations, and/or methylation of the A20
      promoter in various lymphoma entities. METHODS AND RESULTS:   We generated a
      monoclonal antibody against the C-terminus of A20 (Ber-A20) and investigated full
      length A20 expression of normal lymphoid tissue and lymphomas for the first time.
      We identified loss of A20 expression in tumour cells of 24% of classical Hodgkin
      lymphoma, 27% of diffuse large B-cell lymphoma, 20% of chronic lymphocytic
      leukaemia, 19% of follicular lymphoma, 13% of mantle cell lymphoma and 8% of
      primary mediastinal B-cell lymphoma cases by immunohistology. Loss of A20
      expression rarely occurred in T-cell non-Hodgkin lymphoma. CONCLUSIONS:   Our
      data are in agreement with cytogenetic and molecular analyses. Among 21 cases of
      ocular adnexal marginal zone lymphomas with known A20 mutation status, we
      detected complete absence of A20 expression, whereas cases with wild-type A20
      were weakly A20-positive. We demonstrate that A20 loss can be detected by
      immunohistology with a sensitivity similar to that of complex molecular and
      genetic methods.

PMID- 22393905
TI  - Five-year trends of second-hand smoke exposure in Greece: a comparison between
      complete, partial, and prelegislation levels.
AB  - BACKGROUND: Our aim was to assess second-hand smoke (SHS) exposure in hospitality
      venues after the smoke-free legislation implemented in September 2010 in Greece
      and to compare with when a partial ban was in place and in 2006 when no ban was
      in place. METHODS: Hospitality venues were prospectively assessed for their
      indoor concentrations of particulate matter (PM(2.5)) during the partial ban
      phase (n=149) and the complete ban phase (n=120, 80% followed up), while overall
      and matched by venue comparisons were also performed (no ban vs. partial ban vs.
      complete ban). Comparisons with previously collected data in 2006 when no ban was
      in place also was performed. RESULTS: Indoor air levels of PM(2.5) attributable
      to SHS dropped following the transition from a partial to a complete ban by 34%
      (137 MUg/m(3) vs. 90 MUg/m(3), p=0.003). This drop was larger in bars (from 195
      MUg/m(3) to 121 MUg/m(3)), than in cafes (124 MUg/m(3) vs. 87 MUg/m(3)) or
      restaurants (42 MUg/m(3) vs. 39 MUg/m(3)). PM(2.5) concentrations between 2006
      (no ban) and the partial ban of 2010 were also found to decrease by 94 MUg/m(3);
      however, among matched venues, the levels of indoor air pollution were not found
      to change significantly (218 MUg/m(3) vs. 178 MUg/m(3), p=0.58). Comparing the
      2010 complete ban results (n=120) with previously collected data from 2006 when
      no ban was in place (n=43), overall PM(2.5) concentrations were found to fall
      from 268 MUg/m(3) to 89 MUg/m(3), while a matched analysis found a significant
      reduction in PM(2.5) concentrations (249 MUg/m(3) vs. 46 MUg/m(3), p=0.011).
      CONCLUSION: The complete ban of smoking in hospitality venues in Greece led to a
      reduction in SHS exposure, in comparison to when the partial ban or no ban was in
      place; however, exposure to SHS was not eliminated indicating the need for
      stronger enforcement.

PMID- 22393904
TI  - Beneficial and adverse psychotropic effects of antiepileptic drugs in patients
      with epilepsy: a summary of prevalence, underlying mechanisms and data
      limitations.
AB  - Antiepileptic drugs (AEDs) can have both beneficial and adverse psychotropic
      effects. They act on neurotransmitter systems, neuronal ion permeability and
      other targets, although the exact mechanisms are not generally fully elucidated.
      A systematic review of the literature reveals evidence for both positive and
      negative effects on depression, anxiety, aggression, psychosis and sleep in
      patients with epilepsy. Topiramate, vigabatrin, levetiracetam, tiagabine and
      zonisamide have been associated primarily with adverse psychotropic effects,
      whilst gabapentin, pregabalin, lacosamide and lamotrigine, in particular, have
      demonstrated a more beneficial psychotropic profile, especially with regard to
      affective symptoms. This review, however, identifies specific methodological
      issues with studies that have reported on the psychotropic effects of AEDs,
      suggesting that some of the findings might be inconclusive or unreliable because
      of confounding factors, particularly the presence of psychiatric history. More
      rigorous double-blind, randomized, placebo-controlled trials on larger numbers of
      patients with epilepsy, with clear inclusion/exclusion criteria, that are
      specifically designed to investigate psychotropic changes are more likely to
      produce results that inform clinical practice and direct future research.

PMID- 22393906
TI  - Delivery of high solubility polyols by vibrating mesh nebulizer to enhance
      mucociliary clearance.
AB  - BACKGROUND: Inhaled dry powder mannitol has established in vivo therapeutic
      efficacy for enhancing mucociliary function. However, a single dose necessitates
      multiple inhalations of a sizeable powder mass. Nebulization of mannitol by
      vibrating mesh devices has recently been shown in vitro to impart similar dosing
      in a comparable or lesser treatment time. Nevertheless, the limited solubility of
      mannitol restricted fluid concentrations to 150 mg/mL. The present study examines
      the feasibility of higher solubility polyols that presumably possess similar
      therapeutic properties to mannitol but deliverable at higher concentrations to
      shorten treatment time. A secondary aim is to compare delivery by two
      commercially available mesh nebulizers-the Aeroneb(r) Go and PARI eFlow Rapid.
      METHODS: A series of formulations containing three polyols (mannitol, sorbitol,
      and xylitol) of increasing concentration in 1% w/v sodium chloride were
      nebulized. Aerosol characteristics and treatment times were determined primarily
      by laser diffraction. RESULTS: RESULTS indicate viscosity is the primary
      determinant of vibrating mesh nebulizer performance. For both nebulizers, xylitol
      334 mg/mL exhibits the greatest osmolar output-double that of 150 mg/mL mannitol.
      CONCLUSIONS: A nebulized xylitol solution has potential clinical application for
      promoting rapid mucociliary clearance. Both vibrating mesh nebulizers facilitate
      quick treatment times. Future in vivo studies would compare the efficacy of
      nebulized xylitol to commercial hyperosmolar agents and establish any potential
      polyol-associated antibacterial activity.

PMID- 22393907
TI  - Targeted aerosolized delivery of ascorbate in the lungs of chlorine-exposed rats.
AB  - BACKGROUND: Chlorine (Cl(2))-induced lung injury is a serious public health
      threat that may result from industrial and household accidents. Post-Cl(2)
      administration of aerosolized ascorbate in rodents decreased lung injury and
      mortality. However, the extent to which aerosolized ascorbate augments depleted
      ascorbate stores in distal lung compartments has not been assessed. METHODS: We
      exposed rats to Cl(2) (300 ppm for 30 min) and returned them to room air. Within
      15-30 min postexposure, rats breathed aerosolized ascorbate and desferal or
      vehicle (mean particle size 3.3 MUm) through a nose-only exposure system for 60
      min and were euthanized. We measured the concentrations of reduced ascorbate in
      the bronchoalveolar lavage (BAL), plasma, and lung tissues with high-pressure
      liquid chromatography, protein plasma concentration in the BAL, and the volume of
      the epithelia lining fluid (ELF). RESULTS: Cl(2)-exposed rats that breathed
      aerosolized vehicle had lower values of ascorbate in their BAL, ELF, and lung
      tissues compared to air-breathing rats. Delivery of aerosolized ascorbate
      increased reduced ascorbate in BAL, ELF, lung tissues, and plasma of both Cl(2)
      and air-exposed rats without causing lung injury. Based on mean diameter of
      aerosolized particles and airway sizes we calculated that approximately 5% and 1%
      of inhaled ascorbate was deposited in distal lung regions of air and Cl(2)
      exposed rats, respectively. Significantly higher ascorbate levels were present in
      the BAL of Cl(2)-exposed rats when aerosol delivery was initiated 1 h post-Cl(2).
      CONCLUSIONS: Aerosol administration is an effective, safe, and noninvasive method
      for the delivery of low molecular weight antioxidants to the lungs of Cl(2)
      exposed individuals for the purpose of decreasing morbidity and mortality.
      Delivery is most effective when initiated 1 h postexposure when the effects of
      Cl(2) on minute ventilation subside.

PMID- 22393909
TI  - Reduced brain-derived neurotrophic factor (BDNF) mRNA expression and presence of
      BDNF-immunoreactive granules in the spinocerebellar ataxia type 6 (SCA6)
      cerebellum.
AB  - Spinocerebellar ataxia type 6 (SCA6) is an autosomal-dominant neurodegenerative
      disorder caused by a small expansion of tri-nucleotide (CAG) repeat encoding
      polyglutamine (polyQ) in the gene for alpha(1A) voltage-dependent calcium channel
      (Ca(v) 2.1). Thus, this disease is one of the nine neurodegenerative disorders
      called polyQ diseases. The Purkinje cell predominant neuronal loss is the
      characteristic neuropathology of SCA6, and a 75-kDa carboxy-terminal fragment
      (CTF) of Ca(v) 2.1 containing polyQ, which remains soluble in normal brains,
      becomes insoluble in the cytoplasm of SCA6 Purkinje cells. Because the
      suppression of the brain-derived neurotrophic factor (BDNF) expression is a
      potentially momentous phenomenon in many other polyQ diseases, we implemented
      BDNF expression analysis in SCA6 human cerebellum using quantitative RT-PCR for
      the BDNF mRNA, and by immunohistochemistry for the BDNF protein. We observed
      significantly reduced BDNF mRNA levels in SCA6 cerebellum (n = 3) compared to
      controls (n = 6) (Mann-Whitney U-test, P = 0.0201). On immunohistochemistry, BDNF
      protein was only weakly stained in control cerebellum. On the other hand, we
      found numerous BDNF-immunoreactive granules in dendrites of SCA6 Purkinje cells.
      We did not observe similar BDNF-immunoreactive granules in other polyQ diseases,
      such as Huntington's disease or SCA2. As we often observed that the 1C2-positive
      Ca(v) 2.1 aggregates existed more proximally than the BDNF-positive granules in
      the dendrites, we speculated that the BDNF protein trafficking in dendrites may
      be disturbed by Ca(v) 2.1 aggregates in SCA6 Purkinje cells. We conclude that the
      SCA6 pathogenic mechanism associates with the BDNF mRNA expression reduction and
      abnormal localization of BDNF protein.

PMID- 22393908
TI  - Imaging the postdeposition dispersion of an inhaled surfactant aerosol.
AB  - BACKGROUND: Aerodynamic forces provide the primary means of distributing aerosol
      medications within the lungs. Partial airway obstructions can limit both air flow
      and aerosol penetration into diseased zones. We hypothesize that low surface
      tension additives may help to disperse aerosol medications after deposition in
      the airways, improving dose uniformity and drug delivery to underventilated
      regions. To test this, we performed a pilot scintigraphy study of surfactant and
      saline deposition and postdeposition dispersion. METHODS: Because inhaled
      antibiotics for cystic fibrosis provide an example of where self-dispersing
      medications may be useful, we administered calfactant and saline aerosols with
      added Technetium 99m sulfur colloid (Tc-SC; 100 nm filtered) on different days in
      randomized order to eight cystic fibrosis (CF) subjects (average FEV(1)%, p=85 +/
      12%). Nebulized delivery was matched (similar aerosol sizes and volume delivery
      rates, fixed breathing patterns). Tc-SC distribution in the lungs was imaged
      continuously for 30 min after delivery. RESULTS: Both aerosols were well
      tolerated. Aerosol distribution was mostly peripheral (58/42%) and initially
      similar for saline and surfactant. Changes in whole lung counts after 30 min were
      also similar. Peripheral lung activity decreased more rapidly on average with
      calfactant though the difference versus saline was not statistically significant.
      Central to peripheral count ratio decreased with saline and increased with
      calfactant and c/p changes approached significance (-0.05 +/- 0.16 vs. 0.10 +/-
      0.10; p=0.07 Wilcoxon). CONCLUSIONS: Our results lack statistical significance,
      but suggest that inhaled calfactant increased peripheral clearance, due to either
      surfactant-based dispersion or mucociliary effects. Further studies are needed to
      define the potential for low surface tension carriers to improve drug delivery.

PMID- 22393910
TI  - Corticosteroid-induced osteoporosis: an update for dermatologists.
AB  - Long-term corticosteroid treatment is the most common secondary cause of bone
      loss. Patients treated with long-term corticosteroid therapy may develop
      osteopenia or osteoporosis, and many have fractures. It is difficult to predict
      which corticosteroid-treated patients will develop significant skeletal
      complications because of variability in the underlying diseases treated with
      corticosteroids, and because of variation in corticosteroid dose over time.
      Corticosteroid therapy causes an alteration in the ratio between osteoprotegerin
      (OPG) and receptor activator of nuclear factor kappa B (RANK) ligand (RANKL),
      which leads to early increased bone resorption for the first 3-6 months, with
      long-term treatment leading primarily to suppression of bone formation. Recently
      published recommendations advise the use of bisphosphonates or teriparatide in
      high-risk patients, depending on fracture risk assessed by bone mineral density
      testing. This article gives an update of current knowledge regarding the
      pathophysiology, clinical presentation and evaluation, and prevention and
      treatment of patients with corticosteroid-induced osteoporosis.

PMID- 22393911
TI  - Antibody validation by combining immunohistochemistry and protein extraction from
      formalin-fixed paraffin-embedded tissues.
AB  - AIMS:   Personalized cancer treatment strategies depend on comprehensive and
      detailed characterization of individual human malignancies. Clinical pathology,
      particularly immunohistochemical evaluation of biomarkers in tissues, is
      considered to be the approved standard for diagnostic and therapeutic decisions,
      having a direct influence on patient management and therapy. Although antibody
      based approaches are established and integrated successfully into both clinical
      and research applications, for personalized treatment regimens new demands have
      been placed on the quality, reproducibility and accuracy of antibody-based
      assays. To ensure the accuracy of specific antigen detection in
      immunohistochemistry, we introduce a novel approach for antibody validation.
      METHODS AND RESULTS:   In a tandem approach we used the same archival tissue of
      interest for antibody validation by combining extraction of immunoreactive
      proteins from formalin-fixed, paraffin-embedded tissue with Western blot analysis
      and immunohistochemistry. This procedure allows for specification of the antigen
      detected and for localization of the protein in the tissue. Of the 32 antibodies
      tested used in research and routine diagnostics, 19 showed reliable specificity
      in both assays. CONCLUSION:   This study emphasizes the advantage of combining
      suitable methods to ensure reproducibility and specific antigen detection. Based
      on our results, we propose a novel step-by-step strategy to validate antibody
      specificity and reduce variability of immunohistochemical results.

PMID- 22393912
TI  - AMBER empirical potential describes the geometry and energy of noncovalent
      halogen interactions better than advanced semiempirical quantum mechanical method
      PM6-DH2X.
AB  - A recently published study on halogen bonding in casein kinase 2 (CK2)-inhibitor
      complexes claimed that the halogen-bond-corrected PM6 semiempirical method (PM6
      DH2X) describes the halogen bonding properties correctly, whereas the AMBER
      empirical potential fails. The current study employs our positive extra-point
      (PEP) approach for halogen bonding, in which the sigma-hole on the halogen atom
      is represented by an extra point of charge. The performance of the two methods in
      describing halogen bonding in halobenzene...Lewis base and CK2-inhibitor
      complexes was reassessed. Compared to basis set superposition error- (BSSE-)
      corrected MP2/aug-cc-pVDZ (with PP functions on the Br and I atoms) data, the
      AMBER force field described the halogen bonding in halobenzene...Lewis base
      complexes slightly better than the PM6-DH2X method. Fifteen polyhalogenated
      benzimidazole inhibitors (taken from a study of Dobes et al.) complexed to CK2
      protein were studied. The binding energies were calculated using the molecular
      mechanical-generalized Born surface area (MM-GBSA) approach. Compared to the
      corresponding experimental data, the AMBER force field yielded much better
      results than the PM6-DH2X method. Finally, the performance of both methods in
      describing C-X...pi-system and C-X...H-O/C interactions was examined. A
      comparison with MP2 data revealed that the PM6-DH2X method failed to describe
      them, whereas the AMBER force field performed well.

PMID- 22393913
TI  - Obtaining an isolate of Ancylostoma braziliense from dogs without the need for
      necropsy.
AB  - Isolation of a specific Ancylostoma species typically requires death of the
      source animal, or holding an animal long enough to collect feces after treatment,
      for worm recovery and identification. The reason for collecting worms is that the
      eggs are not easy to distinguish morphologically. In keeping with the 3 Rs of
      laboratory animal research (reduction, refinement, replacement), the objective of
      this study was to obtain an isolate of Ancylostoma braziliense from 1-time field
      collected samples of canine feces without the need for killing the host. During a
      collection trip to Florida, fecal samples (n  =  148) were collected and
      identified as containing eggs of Ancylostoma species (n  =  64) using centrifugal
      sugar flotation. Eggs from hookworm-positive slides were washed into tubes, DNA
      was extracted, and 2 samples were identified as A. braziliense using restriction
      fragment length polymorphism (RFLP) with Hinf1. Larval cultures were initiated
      from these samples, and larvae from the cultures were returned to New York and
      used to inoculate a purpose-bred kitten with the goal of inhibiting the growth of
      any contaminating Ancylostoma caninum that might be present in the culture. The
      infection was patent at 15 days, and eggs were identified as A. braziliense by
      RFLP and DNA sequencing. Using forceps during endoscopy, 2 adult worms (1 male, 1
      female) were recovered from the cat and identified morphologically as A.
      braziliense . Larvae were cultured from the feces of this cat and used to infect
      a laboratory-reared beagle dog. Additionally, worms recovered from the feces of
      the cat post-treatment were confirmed to be A. braziliense , except for 1 female
      A. caninum containing infertile eggs. The dog (patent 14 days post-infection) was
      also infected with A. braziliense as determined by RFLP and DNA sequencing of
      eggs and cultured larvae. Both the cat and dog were treated, verified to be no
      longer shedding eggs, and then placed into adoptive homes.

PMID- 22393914
TI  - Development and characterization of coated-microparticles based on whey
      protein/alginate using the Encapsulator device.
AB  - The aim of this study is to prepare whey protein (WP)-based microparticles (MP)
      using the Encapsulator((r)) device. The viscosity dependence of the extrusion
      device required to mix WP with a food-grade and less viscous polymer. Mixed
      WP/ALG MP were obtained with the optimized WP/alginate (ALG) ratio (62/38). These
      particles were further coated with WP or ALG using non-traumatic and solvent-free
      coating process developed in this study. Size and morphology of coated and
      uncoated MP were determined. Then, swelling and degradation (WP release) of
      formulations were investigated in pH 1.2 and 7.5 buffers and in simulated gastric
      and intestinal fluids (SGF, SIF) and compared to pure ALG and pure WP particle
      behaviours. At pH 1.2, pure ALG shrank and pure WP swelled, whereas the sizes of
      mixed WP/ALG matrix were stable. In SGF, WP/ALG MP resisted to pepsin degradation
      compare to pure WP particles due to ALG shrinkage which limited pepsin diffusion
      within particles. Coating addition with WP or ALG slowed down pepsin degradation.
      At pH 7.5, WP/ALG particles were rapidly degraded due to ALG sensitivity but the
      addition of a WP coating limited effectively the swelling and the degradation of
      MP. In SIF, pancreatin accelerated MP degradation but ALG-coated MP exhibited
      interesting robustness. These results confirmed the interest and the feasibility
      to produce coated WP-based MP which could be a potential orally controlled
      release drug delivery system.

PMID- 22393915
TI  - Structure flexibility of the Cu2ZnSnS4 absorber in low-cost photovoltaic cells:
      from the stoichiometric to the copper-poor compounds.
AB  - Here we present for the very first time a single-crystal investigation of the Cu
      poor Zn-rich derivative of Cu(2)ZnSnS(4). Nowadays, this composition is
      considered as the one that delivers the best photovoltaic performances in the
      specific domain of Cu(2)ZnSnS(4)-based thin-film solar cells. The existence of
      this nonstoichiometric phase is definitely demonstrated here in an explicit and
      unequivocal manner on the basis of powder and single-crystal X-ray diffraction
      analyses coupled with electron microprobe analyses. Crystals are tetragonal,
      space group I 4, Z = 2, with a = 5.43440(15) A and c = 10.8382(6) A for
      Cu(2)ZnSnS(4) and a = 5.43006(5) A and c = 10.8222(2) A for
      Cu(1.71)Zn(1.18)Sn(0.99)S(4).

PMID- 22393916
TI  - Multiple segmental neurofibromatosis.

PMID- 22393917
TI  - Effect of Streptococcus sanguinis/Porphyromonas gingivalis single and combined
      biofilms upon platelet aggregation.
AB  - OBJECTIVE: To assess the effect of two oral bacteria Streptococcus sanguinis and
      Porphyromonas gingivalis upon platelet aggregation. MATERIALS AND METHODS:
      Streptococcus sanguinis, P. gingivalis, S. sanguniis+P. gingivalis were added to
      platelet-rich plasma and platelet aggregation measured using a platelet
      aggregometer. Platelets were passed through a flow chamber with S. sanguinis, P.
      gingivalis or a biofilm of S. sanguinis and P. gingivalis coated with saliva.
      Platelet adhesion to the chamber was observed under a fluorescence microscope for
      15min. The positive control was platelets treated with adrenaline; the negative
      control was platelets treated with phosphate-buffered saline. RESULTS: The mean
      (+/- s.e.) aggregation magnitude of S. sanguinis and P. gingivalis was 77.7+/
      7.4% and 79.3+/-9.9%, respectively. The aggregation magnitude of S. sanguinis+P.
      gingivalis was 51.3+/-12.9%, which was significantly lower than that for S.
      sanguinis/P. gingivalis (P<0.05). In the flow chamber system, platelets adhered
      to S. sanguinis/P.gingivalis respectively within 3min, and reached a plateau at 5
      15min. Under the condition of the S. sanguinis- and P. gingivalis-saliva biofilm,
      platelet adhesion to the biofilm was significantly reduced at 5-15min (P<0.05).
      CONCLUSIONS: In the static or dynamic flow system, platelets adhered to S.
      sanguinis or P. gingivalis. However, if S. sanguinis was mixed with P.
      gingivalis, the aggregation magnitude (%) was significantly reduced.

PMID- 22393920
TI  - Lyotropic smectic B phase formed in suspensions of charged colloidal platelets.
AB  - Here, we present the first observation of a smectic B (Sm(B)) phase in a system
      of charged colloidal gibbsite platelets suspended in dimethyl sulfoxide (DMSO).
      The use of DMSO, a polar aprotic solvent, leads to a long range of the
      electrostatic Coulomb repulsion between platelets. We believe this to be
      responsible for the formation of the layered liquid crystalline phase consisting
      of hexagonally ordered particles, that is, the Sm(B) phase. We support our
      finding by high-resolution X-ray scattering experiments, which additionally
      indicate a high degree of ordering in the Sm(B) phase.

PMID- 22393919
TI  - Amine-functionalized sol-gel-based lab-in-a-pipet-tip approach for the fast
      enrichment and specific purification of phosphopeptides in MALDI-MS applications.
AB  - Amine-functionalized sol-gels were investigated for the enrichment and
      purification of phosphopeptides from digested protein mixture solutions.
      Tetramethylorthosilicate (TMOS) and N'[3-(trimethoxysilyl)-propyl]
      diethylenetriamine (TPDA) were used in a 1:1 mole ratio in the production of
      amine-functionalized sol-gels. The sol-gel network was then used for
      phosphopeptide enrichment. Phosphopeptide enrichment onto the synthesized amine
      functionalized sol-gels was performed using an enolase digested peptide mixture,
      a beta-casein digested peptide mixture, as well as these digested peptide
      mixtures contaminated 50-fold with bovine serum albumin (BSA). Moreover,
      phosphopeptide enrichment was successfully performed using nonfat milk as a
      highly contaminated and complex material. In each phosphopeptide enrichment and
      purification process, only phosphopeptides were enriched and separated from the
      other digested peptides. Phosphopeptides were adsorbed onto the amine
      functionalized sol-gels at pH 4.0 and eluted at pH 1.0 using trifluoroacetic acid
      (TFA). For phosphopeptide analysis by MALDI-MS, a 2,5-dihydroxybenzoic acid
      matrix containing 1.0% phosphoric acid was used to overcome the degradation of
      phosphopeptides and provide high intensity phosphopeptide protonated molecular
      ion signal intensities. It was also found that phosphopeptide detection limits
      were improved to approximately 10 femtomoles. For rapid and specific
      phosphopeptide enrichment and purification, sol-gel materials were placed in a 10
      MUL pipet tip with glass wool on either side. Phosphopeptide enrichment from
      digested peptide mixtures was performed in a very short time (less than 1 min) at
      subpicomole levels using this novel lab-in-a-pipet-tip approach.

PMID- 22393918
TI  - A goal-directed spatial navigation model using forward trajectory planning based
      on grid cells.
AB  - A goal-directed navigation model is proposed based on forward linear look-ahead
      probe of trajectories in a network of head direction cells, grid cells, place
      cells and prefrontal cortex (PFC) cells. The model allows selection of new goal
      directed trajectories. In a novel environment, the virtual rat incrementally
      creates a map composed of place cells and PFC cells by random exploration. After
      exploration, the rat retrieves memory of the goal location, picks its next
      movement direction by forward linear look-ahead probe of trajectories in several
      candidate directions while stationary in one location, and finds the one
      activating PFC cells with the highest reward signal. Each probe direction
      involves activation of a static pattern of head direction cells to drive an
      interference model of grid cells to update their phases in a specific direction.
      The updating of grid cell spiking drives place cells along the probed look-ahead
      trajectory similar to the forward replay during waking seen in place cell
      recordings. Directions are probed until the look-ahead trajectory activates the
      reward signal and the corresponding direction is used to guide goal-finding
      behavior. We report simulation results in several mazes with and without
      barriers. Navigation with barriers requires a PFC map topology based on the
      temporal vicinity of visited place cells and a reward signal diffusion process.
      The interaction of the forward linear look-ahead trajectory probes with the
      reward diffusion allows discovery of never-before experienced shortcuts towards a
      goal location.

PMID- 22393921
TI  - Factors affecting radiation D-values (D10) of an Escherichia coli cocktail and
      Salmonella Typhimurium LT2 inoculated in fresh produce.
AB  - This study evaluated the effect of produce type, resuspension medium, dose
      uniformity ratio (DUR), and sample preparation conditions (tissue exposure, MAP,
      anoxia) on the D10 -value of an Escherichia coli cocktail (BAA-1427, BAA-1428,
      and BAA-1430) and Salmonella Typhimurium LT2 inoculated on the surfaces of
      tomato, cantaloupe, romaine lettuce, and baby spinach. Produce at room
      temperature were irradiated using a 1.35 MeV Van de Graaf electron beam
      accelerator at 0.2 to 0.9 kGy. The D10-values for E. coli and Salmonella were
      0.20 +/- 0.01 kGy and 0.14 +/- 0.01 kGy, respectively. Bacterial inactivation was
      not affected by produce type as long as the samples were irradiated in unsealed
      bags, the bacteria were suspended in broth, and the sample tissue was exposed.
      Sample location in front of the e-beam source during exposure is crucial. A 20%
      increase in DUR yielded a 53% change in the D10- values. Variations in sample
      preparation, microbiological methods and irradiation set-up, result in variable
      D10-values for different microorganisms on fresh produce. PRACTICAL APPLICATIONS:
      Most irradiation studies disregard the effect of sample handling and processing
      parameters on the determination of the D10-value of different microorganisms in
      fresh and fresh-cut produce. This study shows the importance of exposure of
      sample, resuspension medium, available oxygen, and dose uniformity ratio. D10
      values can differ by 35% to 53% based on these factors, leading to considerable
      under- or over-estimation of the irradiation treatment. Results from this study
      will help to lay firm groundwork for future studies on D10-values determination
      for different pathogens on fruits and vegetables.

PMID- 22393922
TI  - New ultrasonic dissector versus conventional hemostasis in thyroid surgery: a
      randomized prospective study.
AB  - BACKGROUND: The ultrasonic dissector (UD) is an instrument that uses vibration to
      coagulate and cut tissue simultaneously. The main advantage of a UD instrument
      compared with a standard electrosurgical device is represented by minimal lateral
      thermic tissue damage allowing a wide application in thyroid surgery. A new UD
      (NUD), with a tip smaller than 5 mm, might enable a more precise dissection near
      vital structures such as parathyroid glands and recurrent laryngeal nerve. To
      evaluate the NUD during thyroid surgery, a prospective randomized study was
      performed using the new device versus traditional procedures. SUBJECTS AND
      METHODS: Two hundred sixty-one patients underwent various thyroid surgical
      procedures; they were randomly assigned (130 in the NUD group and 131 in the
      conventional hemostasis [CH] group). The two surgical groups were compared in
      age, sex, diagnosis, thyroid size, operative time, drainage volume during the
      first 24-48 hours after surgery, and complications (hypoparathyroidism, damage of
      the recurrent laryngeal nerve, and postoperative pain). RESULTS: The two groups
      were similar regarding age, sex, numbers of lobectomies and total
      thyroidectomies, and numbers of focal and diffuse pathologies. Mean +/- standard
      deviation operative time was shorter in the NUD group compared with the CH group
      for both lobectomy (70 +/- 21 minutes versus 99 +/- 27 minutes; P<.01) and total
      thyroidectomy (91 +/- 37 minutes versus 121 +/- 42 minutes; P=.01) procedures. No
      difference was found regarding the amount of drainage volume for different
      procedures (P=not significant). Postoperative transient (P=.01) and definitive
      (P=.01) hypoparathyroidism occurred more frequently in the CH group than in the
      NUD group. There was a significant difference regarding the transient damage of
      the recurrent laryngeal nerve: 7 patients (5.3%) in the NUD group and 13 patients
      (9.8%) in the CH group (P=.01). There was no difference regarding definitive
      damage to the recurrent laryngeal nerve and pain. CONCLUSION: This NUD may reduce
      the rate of complications (transient and definitive hypocalcemia, transient
      damage of the recurrent laryngeal nerve) and operative time.

PMID- 22393923
TI  - Transabdominal wall deployment for instruments, lights, and micromotors using the
      concept of secured independent tools.
AB  - Use of secured independent tools (SIT) is changing the laparoscopy paradigm,
      which involves the use of instruments inside the abdominal cavity that are
      operated via a port that is larger in diameter than the instrument itself.
      However, in SIT instead of ports we used filaments or cables. Here we describe a
      modified SIT for use in the introduction of sutures or cables inside the
      peritoneum. Cables or sutures are passed through a tunnel made by an intravenous
      catheter and then exteriorized via a 12-mm port for tying, plugging (attaching),
      or connecting to different types of devices such as an endoscopic bulldog,
      alligator clamps, lights, and micromotors. These devices are introduced inside
      the abdomen and remotely operated with cables or filaments. The use of SIT is not
      limited to laparoscopy; it was successfully used in clinical experiences of
      single-port and single-incision laparoscopy and could facilitate natural orifice
      surgery. The technique offers a good force for traction, retraction, and
      mobilization. In addition, it has transmission capabilities for cameras and may
      facilitate the placement of wired microrobotics.

PMID- 22393924
TI  - Initial experience of total thoracoscopic and laparoscopic Ivor Lewis
      esophagectomy.
AB  - BACKGROUND: Morbidity and mortality remain relatively high for transthoracic
      esophagectomy with open thoracotomy. The literature is limited in describing the
      total combined laparoscopic and thoracoscopic Ivor Lewis esophagectomy. The aim
      of this study is to evaluate the outcomes of combined thoracoscopic and
      laparoscopic Ivor Lewis esophagectomy for the treatment of esophageal carcinoma.
      SUBJECTS AND METHODS: This is a retrospective review of 15 patients diagnosed
      with esophageal carcinoma who underwent thoracoscopic and laparoscopic Ivor Lewis
      esophagectomy from August 2009 to August 2011. Eleven patients (73.3%) were
      diagnosed with adenocarcinoma, and 4 patients were diagnosed with squamous cell
      carcinoma. In total, 8 patients (53.3%) received induction chemoradiation. The
      mean follow-up time was 10.5 +/- 1.9 months. Postoperative morbidity and
      mortality were reported. RESULTS: The median age was 71 years old. Fifteen
      patients underwent total thoracoscopic laparoscopic and Ivor Lewis esophagectomy.
      The operative mortality rate was 0%. The mean operative time and estimated blood
      loss were 468 +/- 54 minutes and 182 +/- 67 mL, respectively. The median
      intensive care unit days and ventilator days were 1.0 and 0.0, respectively. The
      median length of stay was 10 days. In total, 3 patients developed complications:
      One contained anastomotic leak managed with an esophageal stent, one chylous
      effusion managed nonoperatively, and one case of postoperative atrial
      fibrillation. The median number of lymph nodes dissected was 11. All of the
      patients had an R0 resection. CONCLUSION: Total thoracoscopic and laparoscopic
      Ivor Lewis esophagectomy is technically feasible, and we were able to achieve
      relatively good initial outcomes without major morbidity and mortality.

PMID- 22393925
TI  - Complete versus partial mobilization of splenic flexure during laparoscopic low
      anterior resection for rectal tumors: a comparative study.
AB  - BACKGROUND: The aim of the current study is to compare the results after partial
      and complete splenic flexure mobilization (SFM). SUBJECTS AND METHODS: The
      records of laparoscopic and hand-assisted laparoscopic procedures for primary
      rectal tumor patients were abstracted from a prospectively designed database. The
      phrenicocolic and splenocolic ligaments were divided via a four-trocar technique
      in the partial SFM group, and dissection was continued with the separation of
      gastrocolic and pancreaticomesocolic attachments via a five-trocar procedure in
      the complete SFM group. The following data were compared between the groups:
      Demographics, intra- and postoperative information, and pathological features.
      RESULTS: In total, 122 cases (77 [63.1%] male, 58.2+/-13.2 years old) who
      underwent a partial (n=36, 29.5%) or a complete (n=86, 70.5%) SFM were included.
      Reservoir creation (48.8% versus 19.4%, P=.003) was more common and conversion
      (8.1% versus 22.2%, P=.039) was less frequent in the complete SFM group, but
      there were significantly more T4 tumors in the partial group (16.7% versus 2.3%,
      P=.008). Demographics, other intra- and postoperative parameters, and
      pathological features were identical. CONCLUSIONS: In our study, complete SFM
      decreased conversion rates, but this finding may be related to the higher rate of
      T4 tumors in the partial SFM group. Complete SFM assures an increase in reservoir
      creation in patients receiving a low anterior resection. Because other parameters
      are identical, the decision for the level of SFM is better left to the surgeon in
      cases undergoing a low anterior resection, but complete SFM may be preferred in
      cases who are candidates for a reservoir formation.

PMID- 22393926
TI  - Initial experience with aspirin use during robotic radical prostatectomy.
AB  - BACKGROUND: New cardiology guidelines recommend antiplatelet therapy for some
      patients with cardiac stents. Aspirin use is relatively contraindicated during
      urologic surgery because of increased bleeding risk. We sought to review the
      outcomes of patients who continued aspirin during robot-assisted radical
      prostatectomy. PATIENTS AND METHODS: Between October 2007 and February 2010, 249
      patients underwent robot-assisted radical prostatectomy by a single surgeon.
      After consultation with the patients' cardiologists, 6 patients had coronary
      artery stents and continued aspirin perioperatively (Group 1), and 7 patients had
      coronary artery stents but did not continue aspirin perioperatively (Group 2).
      The remaining 236 patients had no coronary artery stents and did not require
      continued aspirin (Group 3). We analyzed our patients' preoperative
      characteristics, including age, prostate-specific antigen volume, and D'Amico
      risk, as well as operative time, blood loss, hematocrit changes, transfusion
      requirements, length of hospital stay, and complications. RESULTS: We found no
      differences in operative time, estimated blood loss, changes in hematocrit, or
      length of hospital stay. No patients with any type of cardiac stent required a
      postoperative blood transfusion or had complications requiring more than simple
      anti-emetics, analgesics, or electrolyte correction. Nine patients in Group 3
      required interventions for significant complications. CONCLUSION: Larger studies
      need to be performed to validate these observations.

PMID- 22393927
TI  - The feasibility of laparoscopic resection compared to open surgery in clinically
      suspected T4 colorectal cancer.
AB  - BACKGROUND: The role of laparoscopic resection in patients with clinical T4
      colorectal cancer remains controversial. This study compared the outcome of
      laparoscopic resection for clinical T4 colorectal cancer with that of an open
      approach. SUBJECTS AND METHODS: Forty-three consecutive patients undergoing
      surgery for colorectal cancer with suspected involvement of another organ (T4) by
      computed tomography and/or magnetic resonance imaging were reviewed. Twenty-four
      patients who underwent laparoscopic colorectal resection were matched with 19
      patients who underwent an open approach. All available clinicopathologic
      variables possibly associated with the outcome were compared. RESULTS: Two
      patients (8.3%) who underwent the laparoscopic procedure were converted to the
      open technique. Patients in the open group displayed more advanced pathologic T
      category (P = .008) and underwent more combined operation than patients in the
      laparoscopic group (P = .017). The R0 resection rate was 75% in the laparoscopic
      group and 52.6% in the open group (P = .135). Patients in the laparoscopic group
      displayed a tendency for lower estimated blood loss (P = .083), sooner bowel
      movement (P=.075), and shorter length of hospital stay (P = .089) than patients
      in the open group. No significant differences in postoperative complications were
      observed between the laparoscopic and open groups (20.8% versus 36.8%, P = .246).
      After a median follow-up of 27 months, the 3-year disease-free survival rate in
      the laparoscopic group was found to be not significantly different from that in
      the open group (76.7% versus 58.8%; P=.303). CONCLUSIONS: Laparoscopic colorectal
      resection for T4 colorectal cancer is feasible and has perioperative and short
      term oncologic outcomes similar to those of an open approach. However, further
      studies with long-term follow-up are needed to resolve these issues.

PMID- 22393928
TI  - Strategic laparoscopic surgery for improved cosmesis in general and bariatric
      surgery: analysis of initial 127 cases.
AB  - OBJECTIVE: Strategic laparoscopic surgery for improved cosmesis (SLIC) is a less
      invasive surgical approach than conventional laparoscopic surgery. The aim of
      this study was to examine the feasibility and safety of SLIC for general and
      bariatric surgical operations. Additionally, we compared the outcomes of
      laparoscopic sleeve gastrectomy with those performed by the SLIC technique.
      SUBJECTS AND METHODS: In an academic medical center, from April 2008 to December
      2010, 127 patients underwent SLIC procedures: 38 SLIC cholecystectomy, 56 SLIC
      gastric banding, 26 SLIC sleeve gastrectomy, 1 SLIC gastrojejunostomy, and 6 SLIC
      appendectomy. SLIC sleeve gastrectomy was initially performed through a single
      4.0-cm supraumbilical incision with extraction of the gastric specimen through
      the same incision. The technique evolved to laparoscopic incisions that were all
      placed within the umbilicus and suprapubic region. RESULTS: There were no 30-day
      or in-hospital mortalities or 30-day re-admissions or re-operations. For SLIC
      cholecystectomy, gastric banding, appendectomy, and gastrojejunostomy, conversion
      to conventional laparoscopy occurred in 5.3%, 5.4%, 0%, and 0%, respectively;
      there were no major or minor postoperative complications. For SLIC sleeve
      gastrectomy, there were no significant differences in mean operative time and
      length of hospital stay compared with laparoscopic sleeve gastrectomy; 1 (3.8%)
      of 26 SLIC patients required conversion to five-port laparoscopy. There were no
      major complications. Minor complications occurred in 7.7% in the SLIC sleeve
      group versus 8.3% in the laparoscopic sleeve group. CONCLUSIONS: SLIC in general
      and bariatric operations is technically feasible, safe, and associated with a low
      rate of conversion to conventional laparoscopy. Compared with laparoscopic sleeve
      gastrectomy, SLIC sleeve gastrectomy can be performed without a prolonged
      operative time with comparable perioperative outcomes.

PMID- 22393929
TI  - Staple-line reinforcement with a thrombin matrix during laparoscopic sleeve
      gastrectomy for morbid obesity: a case series.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) represents a valid option for
      morbidly obese patients, either as a primary or as a staged procedure. Staple
      line reinforcement (SLR) is strongly advocated to decrease the chance of
      bleeding. The aim of this article is to report our experience with a new
      technique of SLR using a thrombin-gelatin matrix in a series of morbidly obese
      patients subjected to LSG. SUBJECTS AND METHODS: Patients subjected to LSG using
      a thrombin-gelatin matrix for SLR from April 2010 to April 2011 were included in
      the study. Each patient's record was registered and prospectively collected for
      the analysis. RESULTS: Seventy-four patients were subjected to LSG using a
      thrombin matrix for SLR. There were 56 female and 18 male subjects with a mean
      age of 44.8 years (range, 16-64 years). Mean preoperative body mass index was
      46.2 kg/m(2) (range, 40-72 kg/m(2)). Mean operative time was 74.4 minutes (range,
      58-96 minutes). Mean time for application of the thrombin matrix was 4.8 minutes
      (range, 3.2-6.6 minutes). Mean postoperative hospital stay was 3.4 days (range, 2
      62 days). Mean follow-up was 8.2 months (range, 3-12 months). Mean postoperative
      body mass index was 36.2 kg/m(2) (range, 30-42 kg/m(2)), and mean percentage
      excess weight loss was 34.2% (range, 28.4%-42.8%). We observed two major
      postoperative complications (2.7%): One gastric stump leak (1.3%) and one major
      bleeding from the trocar site (1.3%), both successfully treated by laparoscopic
      re-exploration. CONCLUSION: LSG with a thrombin matrix for SLR is a safe
      operation and a valid alternative to other well-established techniques.

PMID- 22393930
TI  - Sex, drugs and recombination: the wild life of Aspergillus.
AB  - Throughout the eukaryotes, sexual reproduction is an almost universal phenomenon.
      However, within the Kingdom Fungi, this relationship is not so clear-cut. Fungi
      exhibit a spectrum of reproductive modes and life-cycles; amongst the better
      known species, sexual reproduction is often facultative, can be rare, and in over
      half of the known Ascomycota (the moulds) is unknown (Taylor et al. 1999).
      However, over the last decade, it has become apparent that many of these asexual
      mitosporic taxa undergo cryptic recombination via unobserved mechanisms and that
      wholly asexual fungi are, in fact, a rarity (Taylor et al. 1999, 2001; Heitman
      2010). This revolution in our understanding of fungal sexuality has come about in
      two ways: Firstly, sexual reproduction leaves an imprint on fungal genomes by
      maintaining genes required for mating and by generating patterns of mutation and
      recombination restricted to meiotic processes. Secondly, scientists have become
      better at catching fungi in flagrante delicto. The genus Aspergillus is one such
      fungus where a combination of population genetics, genomics and taxonomy has been
      able to intuit the existence of sex, then to catch the fungus in the act and
      formally describe their sexual stages. So, why are sexy moulds exciting? One
      species in particular, Aspergillus flavus, is notorious for its ability to
      produce a diverse array of secondary metabolites, of which the polyketide
      aflatoxins (AF) are carcinogenic and others (such as cyclopiazonic acid) are
      toxigenic. Because of the predilection of A. flavus to grow on crops, such as
      peanuts, corn and cotton, biocontrol is widely used to mitigate infection by pre
      applying nonaflatoxigenic (AF-) strains to competitively exclude the wild-type
      AF+ strains. However, the eventual fate in nature of these biocontrol strains is
      not known. In this issue of Molecular Ecology, Olarte et al. (2012) make an
      important contribution by using laboratory crosses of A. flavus to show that not
      only is AF highly heritable, but AF- strains can become AF+ via crossing over
      during meiosis. This observation has raised the spectre of cross-breeding and non
      mendelian inheritance of AF between native and biocontrol strains of the fungus,
      leading to an increase in the natural diversity of the fungus with perhaps
      unanticipated consequences.

PMID- 22393931
TI  - A mechanistic understanding of ageing revealed by studying the young.
AB  - A main focus within biomedical research is to understand how adverse
      environmental conditions experienced during early development affects lifelong
      health (Barker 1992). Within this context, extensive research in rodent models
      and humans has shown that intrauterine growth retardation (IUGR) caused by
      nutrient restriction during early development is often followed by post-natal
      'catch-up' growth when access to food resources improves. However, this
      accelerated growth rate seems to come at a cost, as metabolic and endocrine
      processes that are programmed during this time cause later-life onset of diseases
      such as obesity, insulin resistance and cardiovascular disease (reviewed in
      Crespi & Denver 2005). In this issue Molecular Ecology, Geiger et al. (2012)
      asked what are the costs of catch-up growth in nutrient-restricted king penguin
      chicks (Fig. 1) by measuring lengths of telomeres, the protective DNA sequences
      at the end of chromosomes, before and after catch-up growth, as the amount and
      rate of telomere sequence loss over time has been associated with reduced
      lifespan in both model and nonmodel organisms (see reviews of Costantini et al.
      2010; Haussmann & Marchetto 2010). Geiger et al. (2011) found that chicks
      entering the post-winter growth season at a smaller size exhibited increased
      growth rates (i.e. catch-up growth) at the cost of increased oxidative stress and
      reduced telomere lengths compared with the chicks entering the growth period at a
      larger size. Furthermore, chicks that did not survive had drastically shorter
      telomere lengths and reduced antioxidant capacities at the beginning of the
      growth period than all other chicks, thereby directly associating telomere length
      to mortality. These results suggest that while catch-up growth allows smaller
      chicks to head off into the world on equal footing with chicks that hatched at a
      larger size, it likely comes at the cost of a shortened lifespan. Thus, this
      study provides a mechanism that supports the antagonistic pleiotropy theory of
      senescence (Promislow 2004).

PMID- 22393933
TI  - Functional maturation of neocortex: a base of viability.
AB  - The term "viability" is not simply a synonymous with being "born alive," but is
      closely related to the capability of having a "meaningful life" and having a
      reasonable period of survival. The definition of "viability" is generally based
      on two major criteria: the biological, which takes into consideration the
      maturity of the foetus, and the epidemiological, which is based on the survival
      rates reported in literature. The neuromaturation of the cerebral cortex is a
      dynamic process promoted by the subplate, a transient population of neurons that
      guides the development of cortical and thalamocortical connections. These
      connections are for example fundamental for cortical processing of sensory
      information and mental processes. The first thalamocortical and cortico-cortical
      connections grows at 23-24 postconceptional weeks, which coincides with the age
      limit for premature baby survival.

PMID- 22393932
TI  - Ethanol triggers sphingosine 1-phosphate elevation along with neuroapoptosis in
      the developing mouse brain.
AB  - Our previous studies have indicated that de novo ceramide synthesis plays a
      critical role in ethanol-induced apoptotic neurodegeneration in the 7-day-old
      mouse brain. In this study, we examined whether the formation of sphingosine 1
      phosphate (S1P), a ceramide metabolite, is associated with this apoptotic
      pathway. Analyses of basal levels of S1P-related compounds indicated that S1P,
      sphingosine, sphingosine kinase 2, and S1P receptor 1 increased significantly
      during postnatal brain development. In the 7-day-old mouse brain, sphingosine
      kinase 2 was localized mainly in neurons. Subcellular fractionation studies of
      the brain homogenates showed that sphingosine kinase 2 was enriched in the plasma
      membrane and the synaptic membrane/synaptic vesicle fractions, but not in the
      nuclear and mitochondrial/lysosomal fractions. Ethanol exposure in 7-day-old mice
      induced sphingosine kinase 2 activation and increased the brain level of S1P
      transiently 2-4 h after exposure, followed by caspase 3 activation that peaked
      around 8 h after exposure. Treatment with dimethylsphingosine, an inhibitor of
      sphingosine kinases, attenuated the ethanol-induced caspase 3 activation and the
      subsequent neurodegeneration. These results indicate that ethanol activates
      sphingosine kinase 2, leading to a transient increase in S1P, which may be
      involved in neuroapoptotic action of ethanol in the developing brain.

PMID- 22393934
TI  - New hope or drawbacks: will chronic kidney disease be treatable with small
      molecules in the near future?

PMID- 22393937
TI  - Chemoenzymatic synthesis of the next generation of ultralow MW heparin
      therapeutics.
AB  - Heparin, a sulfated glycosaminoglycan, is a widely used injectable anticoagulant.
      This polysaccharide is a natural product extracted from porcine intestinal
      tissue. A specific pentasaccharide sequence is responsible for heparin's high
      affinity towards anti-thrombin III, which undergoes a conformational change and,
      as a result, inhibits the blood coagulation Factor Xa, a critical serine protease
      at the convergence on the intrinsic and extrinsic activation pathway of the
      coagulation cascade. Due to its structural complexity and heterogeneity, the
      synthesis of the anti-thrombin III-binding sequence of heparin has been limited
      to a few approaches. The heparin contamination crisis in 2007 has motivated the
      development of alternative methods for the efficient preparation of safe heparin
      products. In this article, we discuss the current methods and recent advances in
      heparin and low MW heparin syntheses and the recent successful chemoenzymatic
      preparation of ultralow MW heparins.

PMID- 22393936
TI  - miRNAs as potential therapeutic targets for age-related macular degeneration.
AB  - Since their recent discovery, miRNAs have been shown to play critical roles in a
      variety of pathophysiological processes. Such processes include pathological
      angiogenesis, the oxidative stress response, immune response and inflammation,
      all of which have been shown to have important and interdependent roles in the
      pathogenesis and progression of age-related macular degeneration (AMD). Here we
      present a brief review of the pathological processes involved in AMD and review
      miRNAs and other noncoding RNAs involved in regulating these processes.
      Specifically, we discuss several candidate miRNAs that show promise as AMD
      therapeutic targets due to their direct involvement in choroidal
      neovascularization or retinal pigment epithelium atrophy. We discuss potential
      miRNA-based therapeutics and delivery methods for AMD and provide future
      directions for the field of miRNA research with respect to AMD. We believe the
      future of miRNAs in AMD therapy is promising.

PMID- 22393938
TI  - Exploiting bacterial iron acquisition: siderophore conjugates.
AB  - Siderophores are chelators synthesized by bacteria and fungi to sequester iron,
      which is essential for virulence and pathogenicity. Since the process involves
      active transport, which is highly regulated, remarkably efficient and often
      microbially selective, it has been exploited as a Trojan Horse method for
      development of microbe-selective antibiotics. Siderophores also have significant
      potential for the development of imaging contrast agents and diagnostics for
      pathogen-selective detection. These promising results demonstrate the versatility
      of natural and synthetic microbial iron chelators and their potential therapeutic
      applications.

PMID- 22393939
TI  - Small-molecule ATP-competitive dual IGF-1R and insulin receptor inhibitors:
      structural insights, chemical diversity and molecular evolution.
AB  - IGF-1R has been recognized as a major target in cancer drug discovery due to its
      strong implications in various stages of tumorigenesis based on accumulated
      preclinical data. Recent research on compensatory crosstalk between IGF-1R and
      insulin receptor (IR) signaling pathways suggests that targeting both IGF-1R and
      IR should result in a more therapeutically beneficial response, than targeting
      IGF-1R alone (e.g., IGF-1R-specific antibodies). These findings provided
      biological rationale and opened the door to the discovery of a variety of small
      molecule dual IGF-1R and IR inhibitors. In this review we summarize the recent
      developments in this field, with a focus on binding modes and binding
      interactions of these inhibitors with IGF-1R and/or IR. Selectivity of these
      inhibitors has been discussed in this context as well. This is an important area
      to be discussed since one of the major challenges in kinase inhibitor drug
      discovery is to build an optimal selectivity profile based on biological
      rationale.

PMID- 22393941
TI  - The antibiotic resistome: challenge and opportunity for therapeutic intervention.
AB  - Despite the relevance of infectious disease as main causes of human morbidity and
      mortality, the development of new antibacterials is not among the highest
      priorities for pharmaceutical companies. Regulatory and economic issues, together
      with the lack of novel targets, might justify the reduced rate of discovery of
      new antimicrobials. With the increasing number of antibiotic resistant pathogens,
      the mechanisms of resistance appear as appealing alternatives for developing new
      drugs. Defining the elements that contribute to the characteristic phenotype of
      susceptibility to antibiotics of a given bacterial species, will serve to find
      those targets. Recent information on the elements forming part of bacterial
      intrinsic resistomes and on the inhibitors of resistance currently under
      development are presented. The possibility of developing new therapeutic
      procedures based on the administration, together with antibiotics of specific
      metabolic intermediates capable of increasing the susceptibility to antibiotics
      by altering bacterial physiology, are also discussed.

PMID- 22393940
TI  - Recent advances and new perspectives in targeting CFTR for therapy of cystic
      fibrosis and enterotoxin-induced secretory diarrheas.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP
      regulated chloride channel localized primarily at the apical surfaces of
      epithelial cells lining airway, gut and exocrine glands, where it is responsible
      for transepithelial salt and water transport. Several human diseases are
      associated with an altered channel function of CFTR. Cystic fibrosis (CF) is
      caused by the loss or dysfunction of CFTR-channel activity resulting from the
      mutations on the gene; whereas enterotoxin-induced secretory diarrheas are caused
      by the hyperactivation of CFTR channel function. CFTR is a validated target for
      drug development to treat these diseases. Significant progress has been made in
      developing CFTR modulator therapy by means of high-throughput screening followed
      by hit-to-lead optimization. Several oral administrated investigational drugs are
      currently being evaluated in clinical trials for CF. Also importantly, new ideas
      and methodologies are emerging. Targeting CFTR-containing macromolecular
      complexes is one such novel approach.

PMID- 22393944
TI  - Advances in nonfouling materials: perspectives for the food industry.
AB  - Fouling of complex food components onto food-processing materials affects food
      quality, food safety, and operating efficiency. Developments in nonfouling and
      fouling-release materials for biomedical and marine applications enable the
      potential for adaptation to food applications; however, challenges remain. The
      purpose of this review is to present different strategies to prevent fouling
      and/or facilitate foulant removal with a critical point of view for an
      application of such materials on food-processing surfaces. Nonfouling, self
      cleaning, and amphiphilic materials are reviewed, including an explanation of the
      mechanism of action, as well as inherent limitations of each technology.
      Perspectives on future research directions for the design of food processing
      surfaces with antifouling and/or fouling release properties are provided.

PMID- 22393942
TI  - Celecoxib and Bcl-2: emerging possibilities for anticancer drug design.
AB  - Celecoxib is a multifaceted drug with promising anticancer properties. A number
      of studies have been conducted that implicate the compound in modulating the
      expression of Bcl-2 family members and mitochondria-mediated apoptosis. The
      growing data surrounding the role of celecoxib in the regulation of the
      mitochondrial death pathway provides a platform for ongoing debate. Studies that
      describe celecoxib's properties as a BH3 mimic or as a direct inhibitor of Bcl-2
      are not available. The motivations for this review are: to provide the basis for
      the development of novel compounds that modulate Bcl-2 expression using celecoxib
      as a structural starting point and to encourage additional biological studies
      (such as binding and enzymatic assays) that would provide information regarding
      celecoxib's role as a Bcl-2 antagonist. The current review summarizes work that
      identifies the role of celecoxib in blocking the activity of Bcl-2.

PMID- 22393945
TI  - A case of unclassified high-grade glioma with polar spongioblastoma pattern.
AB  - Primitive polar spongioblastoma was first described by Russell and Cairns in
      1947. However, the polar spongioblastoma pattern is often seen in many
      neuroepithelial tumors, and this category was deleted in the previous World
      Health Organization (WHO) classification. In 2010, Nagaishi et al. reported on a
      case involving a neuroepithelial tumor with the typical histological pattern of
      polar spongioblastoma and suggested that this tumor might not be suited to any of
      the neuroepithelial tumors in the current WHO classification. We report on an
      autopsy case involving an unclassified high-grade glioma with polar
      spongioblastoma pattern that was very similar to the case described by Nagaishi
      et al. A 44-year-old man who presented with a headache exhibited a tumor of the
      right frontal lobe on MRI. Histological diagnosis of the tumor obtained by gross
      total resection was high-grade glioma, which was composed of the parallel
      palisading of spindle tumor cells expressing GFAP, without microvascular
      proliferation (MVP) and necrosis. Conventional chemoradiotherapy was performed,
      but the case was complicated by cerebrospinal fluid (CSF) dissemination that
      resulted in multiple extraneural metastases through systemic diversionary CSF
      shunting. Finally, the patient died approximately 13 months after the initial
      treatment. Both the cerebral and Douglas pouch tumors that were obtained at
      autopsy were diagnosed as typical glioblastomas, and they were composed of the
      proliferation of atypical astrocytes with MVP and pseudopalisading necrosis
      without the formation of rhythmic palisading. Although the histological findings
      were different from that of the first operation, immunohistochemical and genetic
      profiles demonstrated almost the same results. This tumor was not classified as a
      typical glioblastoma by the initial findings, but it had the nature of a
      glioblastoma. These findings suggest that the tumor might be classified as a new
      subset of glioblastoma called glioblastoma with polar spongioblastoma pattern.

PMID- 22393946
TI  - Enhanced induction of anti-tumor CTLs in vitro by a lentivirus-transduced
      dendritic cell vaccine expressing secondary lymphoid tissue chemokine and mucin
      1.
AB  - AIMS: Dendritic cell (DC)-based cancer immunotherapy requires an immunogenic
      tumor associated antigen (TAA) and an effective strategy for its presentation to
      lymphocytes. Here, we explored whether transduction of DCs with lentiviruses
      (LVs) expressing a fusion protein of secondary lymphoid tissue chemokine (SLC)
      and mucin 1 (MUC1) could stimulate antigen-specific cytotoxic T cells (CTLs) to
      human cancer cells in vitro. MATERIALS AND METHODS: HLA-A2+ peripheral blood
      monocyte-derived DCs were transduced with recombinant lentiviruses LV at
      different multiplicities of infection (MOI), and MUC1, SLC or SLC-MUC1 mRNA and
      protein were detected by RT-PCR and Western blotting, respectively. Transduction
      efficiencies and phenotypes of DCs were evaluated by flow cytometry. Induction of
      T lymphocyte proliferation by DCs was examined with a Cell Count Kit-8 (CCK-8).
      CTL activities against tumor cells were analyzed by lactate dehydrogenase (LDH)
      cytotoxicity and enzyme-linked immunospot (ELISPOT) assays. RESULTS: Stable
      expression of MUC1, SLC and SLC-MUC1 was obtained in DCs transduced with
      recombinant LVs, and the transduction efficiencies were dose-dependent.
      Transduction with LVs did not appreciably change the DC phenotype. CTL induced by
      LV MUC1 DCs potently and specifically lysed the HLA-A2+, MUC1+colon cancer cell
      line HCT-116. Moreover, this cytolytic activity against HCT-116 was enhanced with
      CTL stimulated by LV SLC-MUC1 DCs. CONCLUSIONS: DCs transduced with MUC1 could
      induce effective cytolytic activity against tumor cells in an antigen-specific
      and HLA-restricted fashion in vitro, and SLC promoted MUC1-specific anti-tumor
      activity. The transduction of DCs with LV SLC- MUC1 may be a promising strategy
      in DC-based cancer immunotherapy.

PMID- 22393947
TI  - MicroRNA-663 targets TGFB1 and regulates lung cancer proliferation.
AB  - MicroRNAs (miRNAs) play critical roles in many different cellular processes,
      including metabolism, apoptosis, differentiation, and development. In this study,
      miR-663 was shown to be highly expressed in patients with lung cancer.
      Furthermore, miR-663 contributed to lung cancer cell proliferation of by
      regulating TGFB1, P53, Bax, and Fas directly or indirectly. Our results
      demonstrated that miR-663 plays an important role in the biology of lung cancer
      and may be useful in developing therapies targeting genes.

PMID- 22393948
TI  - Prevalence and characteristics of anemia in patients with solid cancers at
      diagnosis in southwest China.
AB  - PURPOSE: Cancer-related anemia is common and may have myriad causes, but the
      physiological consequences of a low hemoglobin level are similar. Besides
      chemotherapy-induced anemia, it is also important to understand the anemia in
      treatment-naive patients, which may represent a consequence of cancer itself
      and/or cancer complications, and this may help assess anemia risk and facilitate
      appropriate treatment. The purpose of this study was to analyze the prevalence
      and characteristics of anemia in solid cancer patients at diagnosis in a Chinese
      population. METHODS: 1133 patients with newly diagnosed cancers who were admitted
      to West China Hospital of Sichuan University during January 2010 to May 2011 met
      the inclusion criteria. Data on age, gender, change of food intake, the diagnosis
      and the stage of the tumor, bleeding history, the locations of metastasis, and
      blood cell analysis were searched and analyzed. RESULTS: Prevalence of anemia at
      diagnosis of cancers was 18.98% in unclassified cancers. Gastric cancers,
      colorectal cancers, and hepatopancreatobiliary cancers occupied the first three
      ranks in the cohort. Age, decreased food intake, and bleeding history were
      identified as independent risk factors for anemia occurrence. Furthermore,
      decreased food intake was found to be also associated with the severity of
      anemia. CONCLUSION: Our analysis described the prevalence and risk factors of
      anemia in new diagnosed solid cancer patients in China. To deal with cancer
      related anemia, we suggest that it should be important to improve food intake and
      nutrition, while controlling bleeding, especially in elderly patients.

PMID- 22393949
TI  - Quercetin mediated reduction of angiogenic markers and chaperones in DLA-induced
      solid tumours.
AB  - Diet-derived flavonoids, in particular quercetin, may play advantageous roles by
      preventing or/and inhibiting oncogenesis. Evidence suggests that quercetin can
      elicit various properties depending on the cell type. The aim of this study was
      to evaluate its effects on Dalton's lymphoma ascites (DLA) induced solid tumours
      and to identify the target(s) of action. We addressed this question by inducing
      subcutaneous solid tumours in Swiss albino mice and investigated whether the
      quercetin affects essential biological processes that are responsible for tumour
      growth, morphology, angiogenesis and apoptosis. We also studied influence on
      several heat shock proteins (HSPs). Our findings demonstrate that intra-tumour
      administration of quercetin results in decreased volume/weight. Furthermore, we
      demonstrate that quercetin promotes apoptosis of cancer cells by down-regulating
      the levels of Hsp90 and Hsp70. Depletion of these two chaperones by quercetin
      might result in triggering of caspase-3 in treated tumours. Moreover, it also
      down-regulated the expression of major key angiogenic or pro-angiogenic factors,
      like HIF-1alpha and VEGF In addition, H and E staining together with
      immunofluorescence of fixed tumour tissue provided evidence in support of
      increased cell death in quercetin-treated mice.

PMID- 22393950
TI  - Relationship between soy food intake and breast cancer in China.
AB  - AIMS: Soy food intake may be associated with reduced risk of breast cancer, by
      far the most frequent cancer among women, but the results are inconsistent. We
      aimed to investigate the relationship further in Chinese population and to assess
      the importance of hormone receptor status. METHODS: A case-control study was
      conducted with totals of 183 cases and 192 controls recruited from January 2008
      to January 2011 among patients admitted to the General Hospital of PLA and the
      Second Affiliated Hospital of Guangzhou Medical University, China. Trained
      interviewers conducted face-to-face interviews using a structured questionnaire
      to collect information on dietary habits and potential confounding factors.
      RESULTS: The highest relative to lowest soy isoflavone intake was associated with
      a 58% decrease risk of breast cancer (OR=0.42, 95% CI=0.22-0.80). Higher
      consumption of soy protein also decreased breast cancer risk, and the highest
      consumption reduced 54% cancer risk compared with the lowest (OR=0.46, 95%CI=0.24
      0.88). The inverse association between highest intake of soy isoflavone and soy
      protein with the risk of breast cancer was statistically in postmenopausal women
      (OR=0.57, 95%CI=0.29-0.83; OR=0.50, 95%CI=0.38-0.95). In the ER/PR status
      stratified analysis, a significantly reduced risk was observed for ER+/PR+ breast
      cancer among highest intake of soy isoflavone and soy protein, with ORs of 0.47
      and 0.63, respectively. CONCLUSION: Our study suggested that a high intake of soy
      food is inversely associated with breast cancer risk, the effect depending to
      some extent on the hormone receptor status.

PMID- 22393951
TI  - Treatment patterns and outcomes in management of solid cancer patients suffering
      from thrombocytopenia in Penang hospital.
AB  - INTRODUCTION: Thrombocytopenia denotes abnormal decreases in platelet numbers and
      is a major detrimental side effect of the chemotherapy or cancer disease itself
      which cal lead to hemorrhage from vital organ. This is particularly a problem for
      the brain specifically within solid cancer patients and has a great negative
      effect on cancer patients quality of life (QOL). It ranges from mild bleeding
      from small blood vessels to severe bleeding from large blood vessels. The present
      study was conducted to evaluate the effectiveness of treatment guidelines for
      thrombocytopenia among solid cancer patients in Penang hospital and to find
      associations between these treatments and thrombocytopenia onset and severity and
      to suggest changes in the guidelines. METHODS: This retrospective observational
      study, conducted in a government hospital on Penang island included 341 cancer
      patients with thrombocytopenia who were admitted in the period between 2003 to
      2009. The main statistical tests used were Chi-square test and Logistic
      regression test. The level of significance was set at P < 0.05. RESULTS: Of the
      total of 341, 21 (6.2%) showed thrombocytopenia before receiving chemotherapy and
      the remaining 320 (93.8%) after chemotherapy. The majority suffered from moderate
      thrombocytopenia (n=172; 53.8%), followed by mild a (n=97; 30.3%) and finally
      severe (n=51; 15.9%). For treatment, chemotherapy was delayed/ reduced (n=223;
      65.4%) or platelets were transfused (n=51; 34.6%). However, thrombocytopenia
      problems were only temporarily solved. CONCLUSION: Effectiveness of
      thrombocytopenia treatment guidelines was found to be insufficient. It is
      advisable that thrombopoietin be used as a cornerstone even for patients who
      suffer from moderate thrombocytopenia and platelets transfusion should be used
      just for emergency cases when thrombocytopenia leads to a critical situation.

PMID- 22393952
TI  - Prognostic analysis for treatment modalities in hepatocellular carcinomas with
      portal vein tumor thrombi.
AB  - OBJECTIVE: To assess prognostic aspects of treatment modalities for cases of
      hepatocellular carcinoma (HCC) with portal vein tumor thrombi (PVTT). METHOD: 121
      treated cases were retrospectively divided into five groups: 1 (liver
      transplantation); 2 (transcatheter arterial chemoembolization); 3 (hepatectomy
      plus thrombectomy); 4 (hepatectomy plus thrombectomy combined with adjuvant
      chemobiotherapy via portal vein); and 5 (conservative treatment). The Kaplan
      Meier method with difference in survival estimated by Log-rank test was used to
      compare between groups. RESULT: Groups 1-5 had a significantly differing median
      survival times of 7, 7, 10, 16, 3 months (P<0.05), respectively. One- and three
      year survival rates were 30.0% and 10.0%, 20.0% and 0.0%, 47.0% and 22.0%, 70%
      and 20%, and 12% and 4%. CONCLUSION: Surgical resection combined with adjuvant
      chemotherapy via the portal vein is an effective and safe treatment modality for
      hepatocellular carcinoma with portal vein tumor thrombi.

PMID- 22393953
TI  - More than half of senior residents in Tehran have never heard about colorectal
      cancer screening.
AB  - BACKGROUND: Colorectal cancer (CRC) is the third most prevalent malignancy in
      Iran. Although adequate knowledge about CRC and screening tests has a significant
      effect on screening behavior, there is still no clear information in this regard
      in Iran. The aim of the study was therefore to identify knowledge toward CRC and
      obstacles to screening tests among an Iranian population. METHODS: We conducted a
      preliminary analysis with baseline data drawn from an ongoing randomized
      community trial among people aged 50 years and over in municipal district 6 in
      Tehran. A total of 360 members of health houses, who were not being exposed to
      CRC screening tests, completed the baseline survey and randomized to two study
      groups. Data were collected via personal interviews by 12 trained interviewers
      for demographics, knowledge related to CRC, and barriers to screening tests.
      RESULTS: The mean age was 58.0 (+/- 7.13) ranging from 50 to 86 years; 69% were
      female, 52% were unemployed, 65% had completed high school, and 90% had medical
      insurance. A considerable number of respondents stated that they had never heard
      about fecal occult blood test (61%) and colonoscopy (51%) as CRC screening tests.
      In general, participants were more likely to respond the knowledge items
      inaccurately. Four commonly stated reasons for not being screened were "absence
      of clinical symptoms" (29%); "doctor did not recommend the test" (26%); "never
      think of the test" (22%); and "did not think it was needed" (11%). CONCLUSION:
      Our findings indicated that lack of knowledge about CRC and various barriers to
      screening tests exist among Iranians. Our results may facilitate the development
      of effective educational strategies primarily aimed at high-risk people.

PMID- 22393954
TI  - Efficacy and safety of vandetanib, a dual VEGFR and EGFR inhibitor, in advanced
      non-small-cell lung cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: Vandetanib, an oral inhibitor of vascular endothelial growth factor
      receptor and epidermal growth factor receptor signaling, has attracted wide
      interest in treatment of advanced non-small-cell lung cancer (NSCLC). We aimed to
      assess its efficacy and safety via a systematic review and meta-analysis.
      METHODS: Trials comparing vandetanib-based therapy and non-vandetanib therapy for
      advanced NSCLC were identified. Endpoints evaluated were progression-free
      survival (PFS), overall survival (OS), objective tumor response rate (ORR), and
      toxicity. RESULTS: Seven trials including 4,492 patients were included in the
      analysis. As compared with placebo, vandetanib yielded a clear benefit for ORR
      (odds ratio (OR) = 2.04; 95% CI, 1.60-2.61; P <0.001), and a clinically and
      statistically significant 25% improvement in PFS (hazard ratio (HR) = 0.75; 95%
      CI, 0.66- 0.85; P < 0.001). However, these benefits did not translate into a
      significant improvement in OS (HR = 0.95; 95% CI, 0.88-1.04; P = 0.291). Subgroup
      analyses showed that vandetanib 100mg/d was associated with greater antitumor
      activity than 300 mg/d when given in combination with chemotherapy. In addition,
      the pooled results demonstrated no statistically significant difference between
      vandetanib and single-targeted agents in PFS, ORR or OS. Vandetanib was
      associated with more frequent adverse events. CONCLUSIONS: Vandetanib, as
      compared with placebo, significantly increases ORR and PFS, but does not improve
      OS in the treatment of advanced NSCLC. As compared with single-targeted agent,
      vandetanib does not provide any efficacy advantage. Furthermore grade 3 or
      greater toxicity proved greater in the vandetanib arm.

PMID- 22393955
TI  - On-schedule mammography rescreening in the National Cancer Screening Program for
      breast cancer in Korea.
AB  - Breast cancer is the most commonly diagnosed cancer among women in the Republic
      of Korea. However, many women are not aware of the importance of on-schedule
      mammography screening for breast cancer. The objectives of this study were to
      estimate the percentage of women that attended on-schedule mammography
      rescreening, and to examine the factors associated with rescreening, among the
      target screening population (women aged >= 40 years) in Korea. The study
      population was derived from the National Health Insurance (NHI) Corporation
      database for the National Cancer Screening Program (NCSP), and included 2,511,976
      women from the target screening population who attended the NCSP for breast
      cancer in 2005-2006 (baseline). Study participants were followed-up to determine
      whether they attended mammography rescreening after 2 years as recommended. Among
      those who attended mammography screening in 2005-2006, 61.3% were rescreened on
      schedule 2 years later. The odds of being rescreened were the highest in study
      participants aged 60-69 years. NHI beneficiaries with a higher premium were
      significantly more likely to be rescreened than Medical Aid Program recipients. A
      false-positive screening result at baseline adversely affected subsequent
      screening behavior. Furthermore, those who had a history of mammography screening
      before baseline were more likely to return for rescreening. Therefore, assessment
      of a woman's screening history and socioeconomic status, in combination with
      interventions to reduce anxiety, such as involving primary care physicians or
      better informing women about breast cancer and mammography screening, are needed.
      Efforts to reduce false-positive results and improve the quality of mammography
      may also increase compliance with breast cancer screening recommendations.

PMID- 22393956
TI  - Ethanolic extract of fermented Thunb induces human leukemic HL-60 and Molt-4 cell
      apoptosis via oxidative stress and a mitochondrial pathway.
AB  - Houttuynia cordata Thunb (HCT) is a medicinal plant of the Saururaceae family
      which features antimutagenic and antiviral properties. For extraction, the whole
      plants were fermented or non-fermented with yeast and ethanol then the whole
      plants were dried, ground and extracted with 95% ethanol or water. The aims of
      this study were to compare cytotoxic effects, apoptosis induction, and
      mechanism(s) with the ethanolic and water extracts of fermented and non-fermented
      HCT. Cytotoxicity was assessed using the MTT assay in human leukemic HL-60, Molt
      4 and peripheral blood mononuclear cells (PBMCs). Apoptotic death was
      characterized by staining with propidium iodide and examined under a fluorescence
      microscope. Peroxide radical production and reduction of mitochondrial
      transmembrane potential (MTP) were determined using 2',7'
      dichlorohydrofluorescein diacetate and 3,3'-dihexyloxacarbocyanine iodide and
      flow cytometry, respectively. The expression of caspase-9 was identified by
      immunoblotting. The ethanolic extract of fermented HCT was cytotoxic to HL-60
      >Molt- 4 > PBMCs, to a greater extent than the non-fermented preparation and the
      number of apoptotic cells was higher. The alcoholic (fermented) extract produced
      more radicals than the non-fermented in HL-60 cells but the converse was observed
      in Molt-4 cells. Reduction of MTP was found in HL-60 and Molt-4 cells treated
      with the alcoholic (fermented) extract and caspase-9 was cleaved dose-dependently
      in both cells. In conclusion, the alcoholic extract of fermented HCT was more
      toxic to human leukemic cells than the non-fermented and both cell lines
      underwent apoptosis via oxidative stress and a mitochondrial pathway.

PMID- 22393957
TI  - Binding capacity of ER-alpha ligands and SERMs: comparison of the human, dog and
      cat.
AB  - The estrogen molecule is the major risk factor related to mammary gland tumors,
      with estrogen receptor alpha (ER- alpha) as the important target stimulating
      growth. Therefore one alternative approach to treatment of breast cancer is to
      use selective estrogen receptor modulator (SERM), hormonal therapy. In this
      study, the structures of ER- alpha in humans, dogs and cats were predicted using
      the amino acid sequencing data bank and corrected for general protein structures,
      receptor sites and docking by adding 2,344 ligands with 15 SERMs into the
      database and calculating estimated inhibition constants (Ki). Thereby, ranking of
      best ligands of SERMs in humans, dogs and cats could be achieved. The results
      show that the shapes of ER- alpha differ between species but the major pocket
      sites are the same. Bazedoxifene, a new SERM proved to be the best estrogen
      antagonist and ER- alpha inhibitor in all species (human, dog, cat) with the
      lowest Ki. The other good ligands for dogs and cats are Neohesperidin,
      Dihydrochalcone, and Schreiber2. The differences in these protein structures may
      explain why there are only a few SERMs or other ligands which can be used as anti
      cancer drugs.

PMID- 22393959
TI  - A multifactor dimensionality reduction-logistic regression model of gene
      polymorphisms and an environmental interaction analysis in cancer research.
AB  - BACKGROUND: Analysis of interactions between genes and the environment with
      complex multifactorial human disease faces important challenges. Limitations of
      parametric-statistical methods for detection of gene effects that are dependent
      solely or partially on interactions with other genes or environmental exposures
      are key problems. The aim of the study was to investigate the use of multifactor
      dimensionality reduction (MDR) and logistic regression models to analyze the
      effects of interactions between complex disease genes with other genes and with
      environmental factors and to compare the results of these two methods in
      interaction analysis. METHODS: In this case-control study, the two methods were
      applied to analog data of samples from 486 cancer patients and 514 control
      individuals by computer simulation, including 4 environment factors (E1~E4) and 8
      gene polymorphism factors (G1~G8). Non-conditional logistic regression was used
      to analyze risk factors for cancer, and MDR and logistic regression were employed
      to analyze interactions under various conditions. RESULTS: MDR could find high
      level interactions between genes and the environment (E3*G1*G7), but it could not
      find a main effect; conversely, logistic regression better analyzed the main
      effects (E3, G1, and G4) but was limited in its analysis of high-level
      interactions (E3*G1*G7). The results of these two methods with analog data show
      that the gene G1 site, the G4 site, E3, and the E3*G1*G7 interaction may be risk
      factors for occurrence of cancer. CONCLUSIONS: MDR and logistic regression, which
      are the two complementary methods, can be combined to analyze gene-gene (gene
      environment) interactions with good results. This approach should help to
      determine the causes of diseases, such as chronic non-transmittable diseases like
      cancer.

PMID- 22393958
TI  - Secondhand smoke concentrations in hospitality venues in the Pacific Basin:
      findings from American Samoa, Commonwealth of the Northern Mariana Islands, and
      Guam.
AB  - INTRODUCTION: Secondhand smoke (SHS) from burning tobacco products causes disease
      and premature death among nonsmokers. Although the number of laws prohibiting
      smoking in indoor public places continues to increase, millions of nonsmokers in
      the United States (US) and its territories remain exposed to SHS. This study
      assessed indoor air pollution from SHS in hospitality venues in three US Pacific
      Basin territories. METHODS: Air monitors were used to assess PM2.5, an
      environmental marker for SHS, in 19 smoke-permitted and 18 smoke- free bars and
      restaurants in American Samoa, Commonwealth of the Northern Mariana Islands
      (CNMI), and Guam. Observational logs were used to record smoking and other
      sources of air pollution. Differences in average PM2.5 concentrations were
      determined using bivariate statistics. RESULTS: The average PM2.5 level in venues
      where smoking was always permitted [arithmetic mean (AM)=299.98 MUg/m3; geometric
      mean (GM)=200.39 MUg/ m3] was significantly higher (p<0.001) than smoke-free
      venues [AM=8.33 MUg/m3; GM=6.14 MUg/m3]. In venues where smoking was allowed only
      during certain times, the average level outside these times [AM=42.10 MUg/m3;
      GM=41.87 MUg/m3] was also significantly higher (p<0.001) than smoke-free venues.
      CONCLUSIONS: Employees and patrons of smoke-permitted bars and restaurants are
      exposed to dangerous levels of air pollution from SHS, even during periods when
      active smoking is not occurring. Prohibiting smoking in all public indoor areas,
      irrespective of the venue type or time of day, is the only way to fully protect
      nonsmokers from SHS exposure in these environments.

PMID- 22393960
TI  - Epidemiology of cancers of the kidney in an Australian population.
AB  - BACKGROUND: Kidney cancer has a high incidence in Australia by world standards
      but has attracted little public health attention because of its low ranking among
      other cancers as a cause of death. Incidence, mortality and survival trends were
      investigated in this study for an Australian population and cancer control
      opportunities considered. DESIGN: Age-standardized incidence and mortality rates
      were analyzed by broad age category using data from an Australian cancer
      registry. Disease-specific survivals were analyzed using the Kaplan-Meier product
      limit estimate and multivariable Cox proportional hazards regression. RESULTS:
      Incidence rates approximately doubled during 1980-2008, with large increases
      affecting both sexes. Increases were more evident for renal cell and other
      histology types occurring predominantly in adulthood than childhood
      nephroblastomas. The male to female incidence ratio approximated 2:1 but
      decreased over time and was lower in younger than older age groups. The increase
      in mortality rate was smaller (at 25%) and higher in males (at 36%) than females
      (at 7%). Mortality increases were restricted to the age range of 70 years and
      over. Five-year survivals increased from 47% for 1980-84 to 66% for 2000-08 and
      multivariate predictors of high case fatality were older age at diagnosis and
      less recent diagnostic period. Country cases had lower survivals than
      metropolitan cases, although the difference was small. CONCLUSIONS: Increases in
      mortality were smaller than incidence increases, evidently due to offsetting
      increases in case survival, and did not affect the younger age groups. Further
      reductions in tobacco smoking and reducing the prevalence of obesity will be
      important to prevent renal cell carcinomas. Molecular research is advocated to
      develop targeted therapies and potentially, an effective screening technology.
      Cancer registries need to routinely publish their data by histology type to
      enable more detailed global trend analyses. Population registries also need to
      record stage of cancer at diagnosis to facilitate interpretation of changes in
      survival.

PMID- 22393961
TI  - Endostar combined with chemotherapy versus chemotherapy alone for advanced
      NSCLCs: a meta-analysis.
AB  - BACKGROUND: Use of recombinant human endostatin combined with conventional
      cytotoxic therapy to treat tumors has been growing because of evidence of
      increased efficacy. However, whether antiangiogenic therapy combined with
      chemotherapy really benefits patients with advanced non-small cell lung cancers
      (NSCLCs) remains unclear. OBJECTIVES: This study was conducted to evaluate the
      clinical efficacy and safety of rh-endostatin (Endostar) combined with
      chemotherapy in the treatment of NSCLC patients. METHODS: We selected data from
      the Cochrane Library, EMBASE, Medline, SCI,CBM, CNKI, to obtain all clinical
      controlled trials, including the addition of endostar to chemotherapy in advanced
      NSCLC patients. Fifteen trials with 1335 patients were included according to the
      inclusion criteria. All were randomized controlled trials, and two trials were
      adequate in reporting randomization. Seventeen trials did not mention the
      blinding methods. RESULTS: Meta-analysis indicated that the NPE arm
      (Vinorelbine+cisplatin+Endostar) had a different response rate compared with
      NP(Vinorelbine+cisplatin) arm (OR2.16, 95%CI 1.57 to 2.99). The incidences of
      severe leukopenia (OR0.94, 95%CI 0.66 to 1.32) and severe thrombocytopenia (OR
      1.00, 95%CI 0.64 to 1.57) and nausea and vomiting (OR 0.85, 95%CI 0.61 to 1.20)
      were similar in the two arms. The NPE plus radiotherapy (RT) arm had a similar
      response rate compared with NP plus RT arm (OR 2.39, 95%CI 0.99 to 5.79), as were
      the incidences of leukopenia (OR0.83, 95%CI 0.35 to 1.94), thrombocytopenia (OR
      0.78, 95%CI 0.19 to 3.16) and radiation esophagitis (OR 1.00, 95%CI 0.40 to
      2.49). CONCLUSIONS: Our results suggested that in the treatment of advanced
      NSCLC, endostar in combination with platinum-based chemotherapy could improve the
      response rate without obviously increasing side effects.

PMID- 22393962
TI  - Association of Arg72Pro of P53 polymorphism with colorectal cancer susceptibility
      risk in Malaysian population.
AB  - BACKGROUND: Colorectal cancer (CRC) results from the interaction between
      environmental exposures and genetic predisposition factors. AIMS: A case control
      study was designed and to investigate the genotype frequencies of P53Arg72Pro
      polymorphism in Malaysian CRC patients and healthy controls and to determine the
      associated risk of this polymorphism with CRC predisposition. METHODS: In this
      case-control study, peripheral blood samples of 202 sporadic CRC patients and 201
      normal controls were collected, DNA extracted and genotyped using the polymerase
      chain reaction - restriction fragment length polymorphism (PCR-RFLP) technique.
      RESULTS: Genotype analysis showed the frequency of homozygous variant (Pro/Pro)
      genotype (21%) to be significantly higher in cases compared to controls (13%),
      (p=0.013). On examining the association between variant genotypes and CRC risk,
      the Pro/Pro homozygous variant genotype showed significantly higher risk
      association with CRC susceptibility (OR: 2.047, CI: 1.063-4.044, p=0.033). When
      stratified according to age, we observed that, individuals aged above 50 years
      and carriers of pro/pro genotype had significantly higher risk with OR: 3.642,
      CI: 1.166-11.378, p=0.026. CONCLUSIONS: Our results suggest that the codon 72 SNP
      which results in amino acid substitution of Arginine to Proline in cell cycle
      regulatory gene P53, is associated with sporadic CRC risk and carriers of Pro/Pro
      genotype and more than 50 years old may have high susceptibility.

PMID- 22393963
TI  - Aberrant FHIT expression is linked to bladder carcinogenesis and apoptosis.
AB  - The fragile histidine triad gene (FHIT) functions as tumor suppressor in many
      epithelial cell types. Although the exact mechanisms remain unclear, it is
      apparent that in its absence, cell cycle homeostasis is often perturbed resulting
      in the development of soft tissue tumors. Here, we investigated the role of FHIT
      expression in bladder carcinogenesis and progression using immunohistochemistry.
      Bladder carcinoma tissue and the 5637 cell line were also studied for FHIT
      expression by RT-PCR and Western blotting, respectively. FHIT was found to be
      expressed in carcinoma and adjacent normal tissues at both mRNA and protein
      levels, but the 17 kDa FHIT was lower in tumors (P<0.05), this being confirmed
      immunohistochemically. There was a negative correlation between FHIT expression
      and histological grade of bladder transitional cell carcinoma (P<0.05), but no
      clear relationship with clinical stage or relapse (P>0.05). Overexpression of
      FHIT could induce apoptosis in bladder carcinoma 5637 cells, which could be
      enhanced by adding adriamycin (ADR). These findings suggest important roles of
      FHIT in bladder cancer development and provide support for the feasibility of
      FHIT-based gene therapy.

PMID- 22393964
TI  - Detection of serum anti-P53 antibodies from patients with colorectal cancer in
      China using a combination of P53- and phage-ELISA: correlation to clinical
      parameters.
AB  - BACKGROUND: Colorectal cancer is one of the most common malignant tumors in
      China. The aims of this research were to increase the sensitivity of anti-p53
      antibody detection in the sera of patients with colorectal cancer and to assist
      in their diagnosis. METHODS: Sixty-seven non-selected Chinese with colorectal
      cancer were involved in this study. Anti-p53 antibodies in serum were detected by
      ELISA using recombinant human wild- type p53 protein and hybrid phage as the
      coating antigen. Correlations between the anti-p53 antibodies and
      clinicopathological parameters were also analyzed. RESULTS: The detection
      efficiency of anti-p53 antibodies in the patients with colorectal cancer was
      increased (46.3%, 31/67) through the combination of the two ELISA methods
      compared with each method alone. The titer of serum anti-p53 antibodies was not
      associated with clinicopathological parameters, but there was a significant
      correlation between their presence, the CEA level, and the stage of the patient's
      colorectal cancer. CONCLUSIONS: These results demonstrate that combination of the
      two ELISA methods increased the detection rate of anti-p53 antibodies in patients
      with colorectal cancer. This research may provide a useful method to complement
      conventional clinical diagnosis.

PMID- 22393965
TI  - Viscum album L. extract and quercetin reduce cyclophosphamide-induced
      cardiotoxicity, urotoxicity and genotoxicity in mice.
AB  - Possible protective effects of a methanolic extract of Viscum album (VA) and
      quercetin (QE) against cyclophosphamide (CP) induced cardiotoxicity, urotoxicity
      and genotoxicity in mice were evaluated. Mice were administered orally VA (250
      mg/kg/day) and QE (50 mg/kg/day) for 10 days alone or in combination with CP.
      After the same doses of VA and QE given for 7 days, rats were intraperitoneally
      administered CP (40 mg/kg) on days 8 and 9 of the experiment. Cardiotoxic,
      urotoxic and genotoxic effects were examined in serum, heart, bladder and bone
      marrow. Significant decreases in the levels of antioxidant enzymes (superoxide
      dismutase, catalase and glutathione peroxidase), glutathione-S-transferases,
      reduced glutathione and mitotic index were observed. QE completely and VA partly
      ameliorated almost of all the examined parameters when given together with CP.
      Higher total nitrate/nitrite levels were observed in the myocardial tissue
      treated with QE and VA in combination with CP. In addition, the pre-treatment
      with VA and QE together with CP significantly decreased chromosome aberrations
      and aberrant cells compared to CP alone. Results from the current study suggest
      that QE and VA supplementation attenuates CP induced cardiotoxicity, urotoxicity
      and genotoxicity through a mechanism related to their ability to decrease
      oxidative stress and inflammation, and at least in part to its protective effects
      on the cardiovascular system. In addition, VA and QE may play a role in reducing
      cytogenotoxicity induced by anti-neoplastic drugs during cancer chemotherapy.

PMID- 22393966
TI  - Anti-tumor effects of pEgr-1-endostatin-TNF-alpha recombinant plasmid expression
      induced by ionizing radiation.
AB  - PURPOSE: The aim of the present study was to investigate the anti-tumor effect of
      a pEgr-1-endostatin-TNF-alpha recombinant plasmid induced by ionizing radiation.
      METHOD: Three hundred and twenty mice bearing Lewis lung carcinomas were divided
      into four experimental groups: blank control, irradiation treatment, plasmid
      treatment and plasmid combined irradiation treatment. Twenty-four hours after the
      recombinant plasmid was injected locally into the tumors of the mice, they were
      irradiated with 10 Gy gamma -rays. The concentration of TNF-alpha and endostatin
      in the serum of mice was measured by ELISA and tumor growth in each group was
      compared. The tumor microvessel density was examined by H and E staining and
      immunohistochemistry analysis of CD31 positive cells. RESULTS: Radiation could
      induce the expression of pEgr-1-endostatin-TNFalpha. The levels of endostatin and
      TNF-alpha could express steadily for about 4 weeks, with concentrations of 52.6
      +/- 4.19 and 12.0 +/- 0.87 ng/ml respectively, in the second week in combined
      therapy group and maintained at relative higher level in the fourth week than
      other groups (F=29.7, P>0.05). Compared with the control group, the tumor micro
      vessel density was significantly depressed (P>0.05) and tumor growth was
      significantly inhibited (5907.2 +/- 78.6 mm3 vs. 763.5 +/- 12.3 mm3, P >0.05).
      CONCLUSIONS: The expression of pEgr-1-endostatin-TNF-alpha could be induced in
      mice in vivo and exhibited more significant anti-tumor and anti-angiogenesis
      effects than irradiation alone.

PMID- 22393967
TI  - Arm symptoms and overall survival in Brazilian patients with advanced breast
      cancer.
AB  - INTRODUCTION: Advanced breast cancer is a very frequent serious public health
      problem. OBJECTIVE: This study aimed to analyze the prevalence of arm symptoms
      and overall survival in affected patients. METHODOLOGY: A retrospective cohort
      study was accomplished in 196 women presenting with advanced breast cancer. A
      descriptive analysis was carried out by and overall survival probabilities were
      calculated according to Kaplan-Meier method and Cox regression. RESULTS: These
      included 196 woman had a medium age of 55.9 years, the majority being obese
      (71.3%) and having a IIIB clinical staging (52.3%). The most prevalent arm
      symptoms were pain (54.6%), paresthesia in upper limb (8.5%), lymphedema (> 200
      ml) (6.6%), shoulder restriction (4.7%) and axillary web syndrome (0.6%). The
      median follow-up was 18.7 months (SD 7,33), 4.0% of the patients had metastasis
      and 31.6% were dead. The mean free disease survival was 20.4 months (95% CI 18.4
      22.4), and the mean survival time was 26.3 months (95% CI 24.7-28.0). After
      adjusted the association with arm symptom and overall survival for clinical stage
      and presence of distant metastasis, the shoulder restriction was a predict
      variable, were represents the risk 2.59 for worse survival in compared with woman
      with no shoulder restriction (CI 95% 1.06-5.98). CONCLUSION: The population
      studied at this study presented high prevalence of complications earlier than neo
      adjuvant treatment. After controlling for effects of tumor variables, the
      shoulder restriction was statistically associated with poor overall survival
      after 2 years.

PMID- 22393968
TI  - Comparison of breast cancer in Indonesia and Malaysia--a clinico-pathological
      study between Dharmais Cancer Centre Jakarta and University Malaya Medical
      Centre, Kuala Lumpur.
AB  - INTRODUCTION: The age standardised incidence rate (ASR) of breast cancer in
      Malaysia which is a high middle- income country is similar to Indonesia, a low
      middle-income country. (Globocan 2008) It is however unknown whether the
      presentation of breast cancer differs between these two countries. OBJECTIVE: We
      compared the stage, age at presentation, and pathological characteristics of
      breast cancer between two tertiary hospitals in Indonesia and Malaysia; Dharmais
      Cancer Centre (DCC), which is the national cancer referral centre in Indonesia,
      and University Malaya Medical Centre (UMMC), which is an academic hospital with
      established breast oncology services in Kuala Lumpur. One thousand, one hundred
      and fourteen consecutive women (477 in UMMC: 637 in DCC) who were newly diagnosed
      with breast cancer between January and December, 2010 were included. Patient's
      age, TNM stage at presentation, and pathological characteristics were compared.
      Estrogen receptor (ER) and progesterone receptor (PR) were considered positive if
      10% or greater of invasive cell nuclei were stained while HER2 was considered
      positive with an immunohistochemistry staining intensity of 3+ . Logistic
      regression analyses were performed to identify differences. RESULTS: Median age
      at diagnosis was 52 years in UMMC and 47 years in DCC, whereby patients in DCC
      were more likely to be very young at diagnosis (aged < 35 years) compared to
      their counterparts in UMMC (Odds ratio (OR): 2.09; 95%CI: 1.32-3.31).
      Approximately one third of patients in UMMC presented with TNM stage III or IV,
      compared to 63% in DCC. Patients in DCC were three times more likely to present
      with metastatic breast cancer compared to patients in UMMC (OR: 3.01; 95% CI:
      2.02-4.48). The percentage of low grade tumours in DCC was higher than in UMMC
      (28% vs 11% respectively), and the difference persisted even after multivariate
      adjustment. Although the frequency of ER and PR positivity appeared to be higher
      in UMMC (65% and 55% respectively) compared to DCC (48% and 40% respectively),
      these differences were not statistically significant following adjustment for
      age, stage, HER2 status and grade. The frequency of HER2 positivity was 45% in
      DCC compared to 26% in UMMC, and remained significantly higher even after
      multivariate adjustment (multivariate OR:1.76; 95%CI:1.25-2.47, in DCC compared
      to UMMC). The proportion of triple negative breast cancer was however similar in
      the two centres (19% in UMMC vs 21% in DCC). CONCLUSION: Indonesian women with
      breast cancer seem to present at a younger age and at later stages compared to
      Malaysian women. Their tumors were more likely to be of low grade and HER2
      positive, even after adjustment for other factors, while hormone receptor
      positivity proved similar in the two groups. The higher HER2 positivity rate in
      Indonesian patients warrants further study.

PMID- 22393969
TI  - Polymorphism of DNA repair gene XRCC1 and hepatocellular carcinoma risk in
      Chinese population.
AB  - AIM: We conducted a case-control study in China to clarify the association
      between the XRCC1-Arg399Gln polymorphism and HCC risk. METHODS: A total of 202
      cases and 236 controls were selected from the the Affiliated Hospital of Qingdao
      University from May 2008 to May 2010. Assessment of the XRCC1-Arg399Gln
      polymorphism was based upon duplex polymerase-chain-reactions with the
      confronting-two-pair primer (PCR- CTPP) method. All analyses were performed using
      the STATA statistical package. RESULTS: A significant increase in risk was
      associated with the Arg/Gln genotype (adjusted OR 1.55, 95%CI=1.03-2.57) compared
      with Arg/ Arg. However, the Gln/Gln genotype had non-significant increased risk
      of HCC with adjusted OR (95%CI) of 1.34(0.67-2.38). There was also a significant
      increase with the Arg/Gln genotype among HCC patients above 50 years old
      (OR=1.95, 95% CI=1.14-3.57). Additionally, the risk of HCC was moderately
      increased in drinkers with Arg/Gln genotype compared with never drinkers, and the
      adjusted OR (95% CI) was 1.89 (1.13-3.45). CONCLUSION: This study demonstrated
      that a polymorphism in a DNA repair gene may influence the risk of HCC. The XRCC1
      codon Arg/Gln was this associated with an increased risk of HCC, especially in
      patients above 50 years old and/or with a drinking habit.

PMID- 22393970
TI  - Combination effects of paclitaxel with signaling inhibitors in endometrial cancer
      cells.
AB  - This study was conducted to evaluate and compare molecular and cellular effects
      of paclitaxel in combination with epidermoid growth factor receptor (EGFR) or/and
      mammalian target of rapamycin( mTOR) inhibitors with two endometrial cancer lines
      HEC-1A and Ishikawa. Treatment was with the EGFR inhibitor RG14620, the mTOR
      inhibitor rapamycin, and the conventional cytotoxic drug paclitaxel, alone or in
      combination. The 50% inhibitory concentration (IC50) and cell viability were
      determined by the MTT assay. Multiple drug effect/ combination indexes (CI)
      analysis was applied to assess interactions between paclitaxel and the two
      inhibitors. Apoptosis and cell cycling were evaluated by flow cytometry analysis.
      Western blotting was performed to evaluate the related protein alteration in
      PI3K/AKT signaling pathway. RG14620, rapamycin and paclitaxel showed obvious dose
      dependent growth inhibition with time. The IC50 of paclitaxel at 24 hours
      decreased significantly when pretreated with low doses of RG14620 and Rapamycin
      alone or in combination. Moreover, combination index (CI) of paclitaxel with each
      inhibitor was larger than 1, indicating a synergistic effect between pairs of
      drugs in these two cell lines. FACS analysis showed the cell apoptosis rate
      increased with a synergistic effect. On Western blotting, activation of PI3K/AKT
      pathway was detected in both two cell lines in the control case. When paclitaxel
      was used as a single-agent or in combinations, the protein expression of PI3K/AKT
      pathway totally abated, especially in HEC-1A cells, suggesting a role in
      chemoresistance. The combination of three drugs induced the greatest over
      expression of caspase-3. Combining targeted inhibitors with cytotoxic
      chemotherapy appears to be a promising strategy for the effective treatment of
      endometrial cancer which merits further clinical investigation.

PMID- 22393971
TI  - Implications of greater short-term PSA recurrence with laparoscopic as compared
      to retropubic radical prostatectomy for Japanese clinically localized prostate
      carcinomas.
AB  - PURPOSE: There is ongoing discussion as to the necessity for certain surgical
      procedures being limited to high through-put institutions. To cast light on this
      question regarding use of open as compared to laparoscopic radical prostatectomy
      (LRP) the present study was conducted focusing on biochemical (PSA) recurrence
      free survival of Japanese patients with clinically localized prostate carcinomas.
      MATERIALS AND METHODS: From April 2004 to December 2010 we identified 579
      patients undergoing LRP (n=245) and retropubic radical prostatectomy (RRP)
      (n=334) who did not undergo immediate adjuvant therapy (radiation and/or
      hormonal) and whose PSA levels were lower than 25 ng/ml. Preoperative prostate
      specific antigen (PSA) level, clinical stage, biopsy Gleason score and
      pathological features were assessed and Kaplan-Meier estimates of biochemical
      recurrence (BCR)-free survival were compared. A Cox regression model analysis was
      performed to determine predictors of biochemical recurrence. RESULTS: Median
      follow up was 35 months(2- 115). On univariate analysis the LRP group had a
      slightly lower pathological T stage (p<0.001), higher biopsy Gleason score
      (p<0.001), but much more organ confined disease (p=0.001) than the RRP group. BCR
      free survival did not significantly differ between LRP and RRP groups with
      preoperative PSA <6, clinical stage T1c,T2a, pathological stage T3 or more,
      biopsy Gleason score of 8 or more, pathological Gleason score of 6 or less and 8
      or more, extra-capsular extension and negative surgical margin. The 3-year BCR
      free survival rates were 91.0%(RRP) and 82.2%(LRP) (p<0.001). CONCLUSION: We
      conclude that in general LRP may be associated with a less positive outcome than
      BCR for resection of low risk prostate cancers. Therefore indications for LRP
      should be very carefully monitored.

PMID- 22393972
TI  - Performance of high-risk human papillomavirus testing in the triage of abnormal
      cervical cytology among Chinese younger women in Shanghai, China.
AB  - OBJECTIVE: This study aimed to evaluate the role of high risk HPV DNA testing in
      identifying Chinese younger women with abnormal cytology at risk of harboring
      cervical intraepithelial neoplasia at grade 2 (CIN2) or worse so as to popularize
      an effective triage strategy for younger women. METHODS: A total of 246 younger
      women aged 25 - 36 years old with abnormal cytology were recruited in our study.
      All were assessed by liquid-based cytology, high-risk HPV DNA test, and
      colposcopy with directed biopsy and endocervical curettage as necessary. Residual
      specimens from liquid-based cytology were subjected to real-time PCR testing to
      identify the presence of 10 high-risk HPV types that are prevalent in China.
      RESULTS: Among the 246 abnormal cytology samples, 97 (39.4%) were found to be
      positive for high risk HPV. A clear association was observed between cytological
      findings and the proportion of patients with positive high risk HPV DNA: namely
      29.8% HPV positivity in the ASCUS group; 43.5% in LSIL group; and 90.0% in HSIL
      group (p<0.01). Overall, high risk HPV test achieved a high specificity (79.8%)
      and PPV (86.5%) for an endpoint of CIN2+, and higher sensitivity (91.3%) and NPV
      (98.7%) for an endpoint of CIN3+. For younger women with ASCUS+ cytology, high
      risk HPV test achieved a higher NPV for CIN2+ and CIN3+ (96.0%, 99.0%). For LISL+
      cytology, high risk HPV testing had a high sensitivity with LSIL (90.0%) and HSIL
      (100%), but there was also a corresponding decrease in specificity. CONCLUSIONS:
      The results indicate that high risk HPV DNA testing is highly sensitive and
      moderately specific for CIN grade 2 or worse in women younger than 36 years. LBC
      primary testing followed by high risk HPV DNA triage improved sensitivity and the
      false-positive rate for cervical cancer screening and are suitable for developed
      regions in China.

PMID- 22393973
TI  - Influence of bladder distension control on postoperative intensity-modulated
      radiotherapy in rectal cancer patients.
AB  - AIMS: A prospective study was undertaken to reduce bladder volume variation and
      the irradiated small bowel injury by irrigating the bladder during postoperative
      pelvic IMRT in rectal cancer patients. METHODS: 12 consecutive patients underwent
      three sets of computed tomography scans during the treatment course: Group I, a
      distended (not empty) bladder before the radiation course; Group II, a distended
      bladder at the end of the fourth week; Group III, an irrigated bladder at the end
      of the fourth week. A seven-field coplanar intensity- modulated radiotherapy plan
      of 50.4 Gy was made to the clinical target volume. The total volume of regions of
      interest and volume within every isodose level, their maximum dose and mean dose
      were analysed. RESULTS: Compared with group I, the median reduction of bladder
      volume was 147.7 cm3 (24.3%), and the median increment of small bowel was 122.4
      cm3 in group II. The volume of small bowel within every isodose level was
      increased (P<0.05). Statistical analysis showed a correlation between the volume
      change of bladder and small bowel. The mean radiation dose (Dmean) of small bowel
      and bladder was increased in group II compared to groups I and III (P<0.05).
      CONCLUSIONS: Bladder volume declines significantly during the course of
      radiotherapy, leading to an increment in irradiated small bowel volume. Bladder
      irrigation is a feasible method to guarantee a consistent bladder volume and
      reduce small bowel radiation exposure.

PMID- 22393974
TI  - Primary tobacco prevention in China--a systematic review.
AB  - OBJECTIVES: This systematic review of randomized controlled trials aims to
      identify and describe primary tobacco prevention programs conducted in China and
      to evaluate their quality and effectiveness. METHODS: Published studies in
      English or Chinese were searched in MEDLINE, EMBASE, GLOBAL HEALTH, PsycINFO,
      Wanfang and CNKI. Eligible studies were randomized controlled trials tailored for
      a Chinese population. Primary preventive non-pharmacological interventions for
      smoking cessation or reduction were evaluated. Trials were included if they
      applied at least one predefined outcome suited for measuring the reduction of
      smoking rates or the reduction of smoking related morbidity. Two reviewers
      independently assessed studies for inclusion. The risk of bias in individual
      studies was evaluated by determining the adequacy of methodological quality
      criteria. RESULTS: A total of 21 eligible studies investigating 53,520 patients
      (range 88 - 30,544) an age between 9.6 and 65 years were identified. All
      interventions were based on some kind of health education programs. In most cases
      standard health advice was given and booklets were distributed. The overall
      methodological quality of the studies was low. Seven studies (33%) showed a
      statistical significant effect of the described intervention in all predefined
      outcomes. CONCLUSION: The documentation of smoking prevention interventions in
      China is not sufficient to develop effective and reliable action programs. A lack
      of quality in the design can be discerned rather than a lack in starting
      interventions. We therefore recommend future interventions to be planned,
      implemented and conducted in compliance with high quality standards for example
      Guideline for Good Clinical Practice. Furthermore for preparing reports of RCT
      findings we recommend the Consolidated Standards of Reporting Trials.

PMID- 22393975
TI  - Polymorphisms in DNA repair gene XRCC1 and increased genetic susceptibility to
      glioma.
AB  - BACKGROUND: The XRCC1 gene encodes the XRCC1 protein, which complexes with three
      other DNA repair enzymes involved in the base-excision repair (BER) pathways.
      Different XRCC1 polymorphisms may increase the risk of cancers by impairing
      interaction with other enzymatic proteins and consequently altering DNA repair
      activity, and result in carcinogenesis. Our study aimed to investigate any
      association between three polymorphisms of the XRCC1 gene at codon 194, 280 and
      399 and potential glioma risk. METHODS: We collected 127 patients with primary
      glioma and 249 controls who requested general health examinations from Union
      Hospital of Tongji Medical College hospital from March 2007 to September 2010. A
      total of 5 ml venous blood was drawn from each subject. The polymorphisms of
      XRCC1 gene at codons 194, 280 and 399 were analyzed based on duplex polymerase
      chain-reactions with the confronting-two-pair primer (PCR-CTPP) method. RESULTS:
      The homozygous Trp/Trp and heterozygotes Arg/Trp variants of codon 194 had a 2.12
      fold and 1.46 fold increased risk of glioma compared to the homozygous Arg/Arg
      wide genotypes. The same effect was found in codon 399, the codon 399 Gln/Gln and
      Arg/Gln genotypes being associated with a 2.24 fold and 1.67 fold increased risk
      in glioma. When comparing the codon 194 Arg/Arg and 399 Arg/Arg genotypes, the
      combination of codon 194 Trp allele and 399 Gln allele had a heavy increase in
      glioma risk (OR=2.87, 95%CI=1.56-6.73). CONCLUSION: The present study provided
      evidence of a potential role for XRCC1 codon 194 and 399 polymorphisms in genetic
      predisposition to glioma among the Chinese population. This analysis of
      correlation of DNA repair genes and glioma may provide a deeper insight into the
      genetic and environment factors for cancer risk.

PMID- 22393976
TI  - Modulatory effects of Beclin 1 on expression of angiopoietin and Tie-2 receptor
      in human cervical cancer cells.
AB  - AIM: To investigate the effect of Beclin 1, an autophagy gene, on the expression
      of angiopoietin (Ang) protein and the Tie-2 receptor in CaSki human cervical
      cancer cells. MATERIALS AND METHODS: Beclin 1 overexpression (pcDNA3.1-Beclin1)
      and knockdown (pSUPER-Beclin1) plasmids were independently transfected into CaSki
      cells, and stably transfected cells were selected. Real-time fluorescence
      quantitative PCR and Western blot analyses were performed to detect the mRNA and
      protein expression of Beclin 1, Ang-1, Ang-2, and Tie-2. MTT assays were employed
      to determine cell proliferation rates. RESULTS: In the cells transfected with
      pcDNA3.1-Beclin1, the expression of Beclin 1, Ang-2, and Tie-2 was markedly
      increased, but expression of Ang-1 was dramatically reduced. MTT assays revealed
      that the proliferation of these cells was also significantly suppressed. In the
      CaSki cells transfected with pSUPER-Beclin1, the expression of Beclin 1, Ang-2,
      and Tie-2 was inhibited. CONCLUSION: Overexpression of Beclin 1 can inhibit the
      proliferation of CaSki cells, which may be attributed to an imbalance among the
      expression of Ang-1, Ang-2 and Tie-2.

PMID- 22393977
TI  - Secondary chromosomal abnormalities of de novo acute myeloid leukemia--a first
      report from the Middle East.
AB  - Secondary chromosome aberrations in de novo acute myeloid leukemia ( AML) are
      less specific and occur in addition to the primary chromosome abnormalities.
      Secondary chromosome aberration in acute nonlymphocytic leukemia has been
      recognized for many years as the most serious long-term complication of malignant
      disease. Our aim in this study was to focus on patients with AML associated with
      secondary chromosomal abnormalities in 127 consecutive Iranian leukemia patients.
      Methotrexate (MTX) cell synchronization and 24h non-stimulated cultures of bone
      marrow cells were applied to determine the incidence of chromosomal aberrations
      and association of specific primary and secondary chromosome anomalies according
      to French American British (FAB) morphological subtypes. The distribution of the
      secondary changes was clearly non-random. The most frequent numerical changes
      were -X, - Y, -7, + 8, -10 and + 22 and the most common structural aberrations
      were i(17q), 9q-, dicentric and marker chromosome. We believe this report is the
      first for de novo AML patients showing secondary chromosomal abnormalities which
      are quite non-random. The findings could contribute to widening knowledge of
      related chromosomal abnormalities.

PMID- 22393978
TI  - Radiation-induced sarcoma in the head and neck region: a clinicopathologic and
      immunohistochemical study of 13 cases.
AB  - OBJECTIVES: To study the clinical and histological features of radiation-induced
      sarcoma in the head and neck (RISHN). METHODS: Medical records of 13 patients
      with RISHN treated at our institution between 1990 and 2011 were studied, and
      paraffin-embedded samples were analyzed by haematoxylin and eosin staining and
      immunohistochemistry to determine mitosis counts and assess expression of Ki-67,
      bcl-2, and survivin. RESULTS: Positive bcl-2 was observed in 12 (100%) and
      survivin in 10 (76.9%) patients. The Ki-67 labeling index ranged from 1% to 90%,
      and it showed significant positive correlation with mitosis count in RISHN
      tissues, based on Spearman analysis. Percentage of distal metastasis with T2b was
      significantly higher than T1b stage (P=0.035). CONCLUSIONS: Stage T2b may be a
      useful indicator for predicting distant metastasis of RISHN. The MIB-1 score may
      be used as a histological grading system for RISHN. In addition, bcl-2 and
      survivin protein may play an important role in pathogenesis and progression of
      RISHN.

PMID- 22393979
TI  - MicroRNA-100 acts as a tumor suppressor in human bladder carcinoma 5637 cells.
AB  - Bladder carcinoma is one of the most common tumors in the world and despite the
      therapy currently available most of the patients relapse. Better understanding of
      the factors involved in disease pathogenesis would provide insights for the
      development of more effective strategies in treatment. Recently, differential
      miRNA expression profiles in bladder urothelial carcinomas identified miR-100
      down-regulation and miR-708 up-regulation among the most common alterations,
      although the possible influence of these miRNAs in the control of basic
      mechanisms in bladder tumors has not been addressed. In this context, the present
      study aimed to evaluate the in vitro effects of miR-100 forced expression and miR
      708 inhibition in the bladder carcinoma cell line 5637. Our results showed that
      overexpression of miR-100 significantly inhibited growth when compared to
      controls at both times tested (72 and 96 hours, p<0.01) with a maximum effect at
      72 hours reducing proliferation in 29.6 %. Conversely, no effects on cell growth
      were observed after inhibition of miR-708. MiR-100 also reduced colony formation
      capacity of 5637 cells by 24.4%. No alterations in cell cycle progression or
      apoptosis induction were observed. The effects of miR-100 on growth and
      clonogenicity capacity in 5637 cells evince a possible role of this miRNA in
      bladder carcinoma pathogenesis. Further studies are necessary to corroborate our
      findings and examine the potential use of this microRNA in future therapeutic
      interventions.

PMID- 22393980
TI  - Prognostic impact of risk factors in patients with gastric cancer in Iran.
AB  - BACKGROUND: Gastric cancer (GC) is one the most common causes of death worldwide.
      Despite the decreasing rate of GC in the world through recent years, it is still
      the most common cancer in men and the fourth in the general population in Iran.
      This study aimed to assess the survival of patients with GC and to determine
      prognostic factors. MATERIALS AND METHODS: A total of 471 patients with GC were
      followed from 21 March 2003 to 21 March 2007 in the Cancer Institute of Imam
      Khomeini Hospital. The patients' survival rate was determined by periodical
      refers. The survival period considered as the time from diagnosis up to death or
      the end of the study. The effects of gender, age at diagnosis, tumor site,
      pathologic stage of disease, type of treatment used, and metastasis were
      evaluated by log-rank test in a univariate analysis. In addition, all the
      variables were evaluated simultaneously by the Cox proportional hazard (PH)
      model. Data were analyzed using SPSS 16 software. RESULTS: 357 (75.8%) out of 471
      patients were male and 153 cases (32.5%) experienced death. The mean and median
      ages at diagnosis were 58.5 and 60.7 years respectively. Also, the survival mean
      and median were 41.8 ( 3.1) and 27 (1.7) months respectively. Gender, type of
      treatment, pathologic stage, the degree of differentiation were significantly
      related to survival. CONCLUSIONS: There was a potential effective role of age at
      diagnosis, gender of patients and pathologic stage of disease in cancer therapy
      in this part of Iran. Therefore, to reduce the risk of death in patients with GC,
      early diagnosis of patients at a younger age and also in primary stages must be
      targeted.

PMID- 22393981
TI  - A novel and cost-effective method for early lung cancer detection in immunized
      serum.
AB  - BACKGROUND: The aim of this study was to detect early lung cancer rapidly with a
      novel and cost-effective quartz crystal microbalance (QCM) immunosensor.
      MATERIALS AND METHODS: Murine Lewis lung carcinoma LL/ 2 cells were first
      cultured onto the surface of 10MHz 3rd overtone AT-cut quartz crystals in
      Dulbecco's modified Eagle medium, and then the serum sample of LL/2 cell
      immunized rabbits was also dripped onto the quartz crystal surface center by
      micro-injector. In addition, non-immune rabbit serum was used as a negative
      control. The additional mass of the crystal which caused by specifically
      adsorbing antibody results in a change in resonant frequency. A frequency counter
      was employed to monitor the frequency variation. Then the antibody content of the
      LL/2 cell can be detected rapidly through changed frequency. RESULTS: The
      antibody contents of the LL/2 adsorbed on the surface of six quartz crystals were
      155ng, 55ng, 55ng, 32ng, 32ng, 0ng, respectively. The results showed that the
      LL/2 antibodies could be detected if they exist in serum at nanogram level with a
      high detection precision and a positive detection rate of above 80%. CONCLUSIONS:
      Our test results reveal that the proposed method has potential application in
      detection of early lung cancer.This novel detection method might be particularly
      suited for health screening of the general population.

PMID- 22393982
TI  - Validity of different cytological grading systems of breast carcinoma--a hospital
      based study in South India.
AB  - INTRODUCTION: With increase in the incidence of breast carcinoma, fine needle
      aspiration cytology (FNAC) has began to play a major role in diagnosing and
      grading. The study was aimed at validating the different cytological grading
      systems like Hunt's cytological grading (HCG), modified black grading (MBG),
      Robinson's cytological grading (RCG) and Masood's cytology index (MCI) in
      comparison with a modified Bloom-Richardson (MBR) histopathological grading.
      METHODS AND MATERIAL: Fifty breast carcinoma cases were prospectively studied by
      comparing various cytological grading methods with histopathological grading over
      a period of three years. All statistical analyses were carried out with the Epi
      info package. RESULTS: The concordance rate of RCG was 82% which is highest of
      all, while that of MBG was 68%. HCG and MCI were not comparable with MBR due to
      insufficient grading. CONCLUSIONS: RCG for breast carcinoma is validated. A
      consensus for a standard cytological grading method similar to the gold standard
      MBR histological grading must be arrived at based on conducted comparative
      studies and has to be inculcated in routine cytology reports.

PMID- 22393983
TI  - Risk factors of nasopharyngeal carcinoma in Turkey-an epidemiological survey of
      the Anatolian Society of Medical Oncology.
AB  - BACKGROUND: Nasopharyngeal carcinoma is a rare disease in most parts of the world
      with a multifactorial etiology involving an interaction of genetic, viral,
      environmental and dietary risk factors. This is the first epidemiologic study
      aimed to evaluate the risk factors of nasopharyngeal carcinoma in the Turkish
      population. METHODS: We conducted a multicentric, retrospective, case-control
      study using a standardized questionnaire which captured age, sex, occupation,
      household type, blood group, dietary habits, smoking, alcohol consumption and
      oral hygiene. The study included 183 cases and 183 healthy controls matched by
      sex and age. Multiple logistic regression and univariate analysis were employed.
      RESULTS: The peak age incidence was 40-50 years and the male to female ratio was
      2:1. We observed significant associations between elevated nasopharyngeal
      carcinoma risk and low socioeconomic status, rural household type (OR:3.95,
      p<0.001), farming (OR:4.24, p<0.001) and smoking (OR:3.15, p<0.001). Consumption
      of french fries (OR:1.44, p=0.024), fried meat (OR:1.05, p=0.023) and tea
      (OR:5.55, p<0.001) were associated with elevated risk, while fresh fruit
      consumption was associated with reduced risk (OR:0.59, p=0.011). An irregular
      meal pattern was also a risk factor (OR:1.75, p=0.012). There were no significant
      associations between consumption of grain, diary products, alcohol and
      nasopharyngeal carcinoma risk (p>0.05); furthermore salty foods had a borderline
      p value (OR:2.14, p=0.053). Blood type A increased the risk (OR:2.03, p=0.002)
      while blood type 0 was a protective factor (OR:0.53, p=0.009). Rare habit of
      teeth brushing (OR:6.17, p<0.001) and >= 10 decayed teeth before diagnosis
      (OR:2.17, p<0.001) increased the risk. CONCLUSIONS: The nasopharyngeal carcinoma
      risk factors described in the literature are also applicable for the Turkish
      population. People with type A blood are at risk in Turkey. Salted foods have
      also a border risk out of the endemic regions. This is the only study showing
      that poor oral hygiene is a serious risk factor for nasopharyngeal carcinoma.

PMID- 22393984
TI  - Knowledge, attitude and practice (KAP) concerning cervical cancer and screening
      among rural and urban female healthcare practitioners in the Democratic People's
      Republic of Korea.
AB  - BACKGROUND AND OBJECTIVE: Little is known about cervical cancer (CC) in the
      Democratic People's Republic of Korea (DPRK). This study examines the knowledge,
      attitudes and practices (KAP) concerning CC and screening among female health
      care practitioners (HCPs), and whether differences exist between rural and urban
      HCPs. METHOD: In a descriptive cross-sectional study, a purposive sample of 200
      women HCPs from 128 health care centers in 6 provinces of DPRK was interviewed
      using a standardized questionnaire. RESULTS: 98% of HCPs were aware of CC.
      Awareness of the national CC policy was significantly lower in rural (44%) than
      urban (62%) respondents (p<0.05). Fewer rural (71%) than urban (89%) HCPs knew of
      cervical cytology (p<0.05). Around 30% of HCPs were aware of the association
      between CC and human papillomavirus infection. Only 13% of HCPs had ever had a
      cervical cytology smear. Only 4% of rural and 21% of urban practitioners (p<0.05)
      provided cytology; all used unaided visual inspection of the cervix without
      staining to determine whether cytology testing was indicated. For all, screening
      intervals depended on presence of symptoms. CONCLUSION: Misconceptions and
      ineffective clinical practices regarding screening need to be urgently addressed
      among both rural and urban HCPs. There are no major differences between rural and
      urban HCPs regarding their KAP.

PMID- 22393986
TI  - Incidence and survival of cancers in the elderly population in Iran: 2001-2005.
AB  - OBJECTIVE: This study concerns the incidences of different types of registered
      cancers among the Iranian elderly population. The aim was to estimate the 5-year
      survival of cancers between 2001 and 2005, according to elderly age groups and
      history. Since data on the health status of the Iranian elderly are non existent,
      these findings will, in part, fill the gap in geriatric knowledge in Iran.
      METHODS: Data from the national cancer registry department of the Ministry Health
      and Medical Education (MOH and ME), which are pathology-based registration data,
      were used as the main source of information on incident types of cancers in Iran
      from 2001-2005. The coverage rate was nearly 80% of majority types of cancers and
      almost 100% of pathologically diagnosed forms of cancers in the elderly. Survival
      estimates calculated by Kaplan-Meier method. The survival probability was
      calculated for the overall cohorts, as well as gender and anatomical sites of
      tumor. RESULTS: The highest incidence of cancer in five-year cohort was for skin
      cancer among the elderly population. The youngest aged group (60-74) years had
      high incidences (64.3%) of all types of cancers. Incidence rates of breast and
      thyroid cancers in old women were greater than in elderly men. In terms of
      survival rate, relative risk reflects significant association with gender (RR=
      1.03; 95% CI: 0.84-0.95), P = 0.00. CONCLUSION: Based on the results in this
      study, the incidence of cancers in the elderly population increases with age. The
      mean age of the five-year survival cohorts was 88.2 years old. The incidence
      rates of cancers in old men are generally higher than in elderly women.

PMID- 22393985
TI  - Knowledge, attitude and practice (KAP) concerning cervical cancer and screening
      among rural and urban women in six provinces of the Democratic People's Republic
      of Korea.
AB  - BACKGROUND: This study assessed women from the Democratic People's Republic of
      Korea for: (i) their level of knowledge of cervical cancer and attitudes and
      practices concerning cervical screening (KAP); and (ii) differences in KAP
      between rural and urban groups. METHODS: In a descriptive cross-sectional study,
      a purposive sample of 200 women in 6 provinces of DPRK (rural: n=99, urban:
      n=101) were interviewed using a standardized questionnaire. Differences between
      proportions were assessed using the chi2 test. Significance was defined as
      p<0.05. RESULTS: 63% of rural and 60% of urban participants had heard of cervical
      cancer (p>0.05). 42% knew that it is the most common cancer of the female
      reproductive tract, 55% knew that all women are at risk, but only 36% were aware
      of cervical cancer's preventability. Some 13% of rural and 29% of urban
      respondents had heard of cervical cytology testing (p<0.001). Only 6% of
      participants had ever received a cervical cytology smear. Among the reasons for
      not screening, 48% mentioned a lack of awareness of cervical cytology; 47% their
      dislike of pelvic examinations; 17% of rural and 31% of urban interviewees
      reported the absence of symptoms (p<0.05); and 62% of rural and 0% of urban women
      mentioned travelling long distances to service delivery points (p<0.001).
      CONCLUSIONS: There is a reasonable level of knowledge of cervical cancer among
      North Korean women; however, there are major gaps regarding awareness of its
      preventability and actual uptake of cytology screening services. There are no
      significant differences between rural and urban women with regard to their KAP.
      Large scale health promotion campaigns are needed to educate women and the
      community about cervical cancer and its preventability through screening. The
      national health care system needs to ensure that screening services are
      effective, accessible, feasible and acceptable to women.

PMID- 22393987
TI  - Water pipe (shisha) smoking and associated factors among Malaysian university
      students.
AB  - OBJECTIVE: The objective of this study was to determine the prevalence of
      waterpipe (shisha) smoking and associated factors among Malaysian university
      students. METHODOLOGY: A total of 200 university students from Management and
      Science University participated in this study. The survey was conducted by simple
      random sampling by randomly distributing self-administered questionnaires to the
      library, cafeterias and classes. The protocol of this study was approved by the
      ethics committee of Management and Science University. Consent forms were
      obtained from the students before they answered the questionnaire. Statistical
      analyses were performed using the Statistical Package for Social Science (SPSS)
      version 13. with the Student's t-test for comparison of the mean practice and
      backward multiple linear regression for multivariate analysis. RESULTS: The
      majority of the subjects were male, single, Malay and from urban areas (61.5%,
      94.5%, 66%, 76.5%; respectively). In this study 30% of the study participants
      were shisha smokers. Regarding knowledge about shisha smoking, the majority
      (48.5%) mentioned that shisha is less harmful than cigarettes and 55% reported
      that shisha is less addictive. Univariate analysis showed that age, race, sex and
      income significantly influenced the practice of smoking shisha among university
      students (p=0.019, p=0.002, p=0.001, p=0.018; respectively). For multivariate
      analysis, income and gender demonstrated significant influence (both p=0.001).
      CONCLUSION: There was a high prevalence of shisha smoking among Malaysian
      university students and knowledge about the dangers is low. Income and gender
      significantly influenced the practice of smoking shisha in our population.
      Banning of smoking including shisha smoking in public places is strongly
      recommended.

PMID- 22393988
TI  - Low activity of manganese superoxide dismutase (MnSOD) in blood of lung cancer
      patients with smoking history: relationship to oxidative stress.
AB  - Lung cancer is the primary cause of cancer death in the world. Although it is
      well established that tobacco smoke causes lung cancer, not all smokers develop
      lung cancer. Manganese superoxide dismutase (MnSOD), a major determinant of
      antioxidants in matrix mitochondria, plays a pivotal role in eliminating anion
      superoxide free radical generated from the tobacco smoke. The aim of this study
      was to analyze the enzyme activity of MnSOD in blood of lung cancer patients with
      a smoking history in relationship to oxidative stress. Samples were taken from
      leukocyte cells of 20 lung cancer patients in Persahabatan Hospital Jakarta.
      Control groups included 50 healthy smokers and 50 non smokers, all aged over 40
      years. The MnSOD activity determined biochemically based on the inhibition of
      xanthin oxidase, of lung cancer patients was lower than the control group's
      (p<0.001). Plasma MDA levels, determined by reaction with thiobarbituric acid
      (TBA), were not significantly different (p=0.479), whereas plasma carbonyl levels
      were elevated (p=0.003). Free radical production in lung cancer patients thus
      appeared high. Smoker controls also tended to exhibit lower MnSOD and higher
      carbonyl radicals than their non-smoking counterparts. Continue cigarette smoke
      exposure may increase production of ROS and bring about a reduction of MnSOD,
      which could play a role in lung cancer development.

PMID- 22393989
TI  - Pathological and clinical characteristics of 1,248 non-Hodgkin's lymphomas from a
      regional cancer hospital in Shandong, China.
AB  - INTRODUCTION: Non-Hodgkin's lymphomas (NHL) in China appear to have many
      characteristics different from those Western countries, but clinical studies to
      provide details have been rare so far. METHODS: This study retrospectively
      analyzed the characteristics of clinical and pathological data for the 1248 NHL
      patients in the Shandong region of China between 2002 and 2010. RESULTS: From
      2002 to 2010, the number of clinical cases of NHL increased year by year. Among
      the total, 64.7% were B-cell NHL, 30.3% were T-cell NHL, including: diffuse large
      B cell lymphoma (DLBCL) (40.9%), extranodal NK/T-cell lymphoma, nasal type (NK/T)
      (10.0%); peripheral T cell lymphoma, unspecified (PTL) (9.2%); follicular
      lymphoma (FL) (6.4%); extranodal marginal zone B cell lymphoma (MALT) (5.4%);
      precursor T lymphoblastic leukemia/lymphoma (T-LBL) (4.5%); and chronic
      lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (3.2%). The average age
      of onset was 47.7 ? 16.3 (18-85), and the male to female ratio was 1.57:1.
      Compared with Shanghai and Shanxi in China, the proportion of NK/T cell lymphoma
      in this region was higher. In comparison with other countries, the FL and CLL/SLL
      in this region were significantly lower, while the incidence of T-cell lymphoma
      was significantly higher than that in the United States and Europe. CONCLUSIONS:
      The clinical and pathological distribution of NHL in Shandong region of China is
      consistent with that of Asian populations, but with significant difference from
      the Western countries. The NK/T cell lymphoma in this region was significantly
      higher.

PMID- 22393990
TI  - Knowledge, attitude about breast cancer and practice of breast cancer screening
      among female health care professionals: a study from Turkey.
AB  - The awareness of health professionals about breast cancer prevention is of vital
      importance, since their beliefs and behaviors may have a major impact on other
      women. The aim of this study was to investigate the knowledge, and attitudes
      regarding risk factors for breast cancer as well as screening such as breast self
      examination, clinical breast examination and mammography among different groups
      of female health professionals. In this cross- sectional study, 444 female health
      professionals in various health centers located in Corum Province, Turkey, were
      interviewed using a self-administered questionnaire. The mean age was 33.1 +/-
      6.1 and most were married (81.3%). The rate of feeling under risk regarding
      breast cancer among female health personnel was 31.3%. The majority (98.4 %)
      perceived breast self-examination as a beneficial method for the early detection
      of breast cancer. Although 81.3 % of the participants stated that they did breast
      self examination, only 27.3 % reported doing so on a regular basis (performed
      monthly or once per menstrual cycle). The most common reason for not doing breast
      self-examination was the belief that it was not necessary (45.8 %). Of the entire
      group, the rate of having a mammography was 10.1% and the rate of clinical breast
      examination was 24.8%. Health professionals are a direct source of medical
      information to the public. The use of breast self-examination and mammography was
      found lower than expected when considering the fact that participants were health
      care professionals.

PMID- 22393991
TI  - Status of HER2 amplification, polysomy 17 and histopathological features of 425
      Pakistani breast cancer patients.
AB  - HER2 gene amplification in invasive breast cancer is a robust predictive marker
      for response to transtuzumab therapy. This study was undertaken to measure
      concordance between immunohistochemistry (IHC) and FISH for HER2 gene
      amplification in invasive breast tumors, as well as the presence of polysomy 17
      and possible correlation with demographics and histopathological variables,
      including ER and PR positivity. A total of 425 cases of infiltrating carcinoma of
      breast (99% IDC-NOS) were studied. HER2 over expression was tested by IHC and
      FISH methods. Association between IHC and FISH in both subsets was calculated by
      amplification ratio including polysomy 17. Out of 425 specimens, 128 (30%) were
      positive for HER2 amplification by FISH test, whereas only 78 (24%) tumors with
      2+  expression showed amplification. In contrast, 39 (74%) demonstrated 3+  IHC
      score and HER2 gene amplification. The histological variables including tumor
      size, tumor type, and lymph node involvement did not influence the outcome of
      FISH analysis. The ER and PR status showed significantly greater positivity in
      patients negative for HER2 amplification. Polysomy 17 was detected in 23.7%
      patients and was positively associated with ER and PR expression (P= <0.05). Our
      study showed a concordance of 24% between 2+  IHC and FISH amplification, while
      in 3+  IHC cases the concordance was 74%. Significant links of HER2 amplification
      was seen with ER andPR negativity and higher tumor grade. In addition, non
      significant correlations were noted with other variables like tumor type, size
      and lymph node status.

PMID- 22393992
TI  - HLA class II variants in Chinese breast cancer patients.
AB  - Alterations of human leukocyte antigen (HLA) class II molecules are relevant to
      the development of breast cancer and metastatic progression. However, the role of
      HLA class II polymorphisms in the pathogenesis and progression of breast cancer
      is unclear. This study aimed to investigate the association between HLA class II
      variants and breast cancer susceptibility and prognosis in a Chinese population.
      Sixteen variants in HLA class II were detected with the Sequenom MassArray(r)
      iPLEX System in 216 breast cancer patients and 216 healthy controls. An
      association analysis based on unconditional logistic regression was carried out
      to determine the odds ratio (OR) and 95% confidence interval (95% CI) for each
      SNP. Stratified analysis by oestrogen receptor (ER) and progesterone receptor
      (PR) status was also performed. Among 16 variants, only seven conformed to Hardy
      Weinberg proportions in the controls. None of these seven variants showed
      statistically significant differences between the case and control groups in this
      Han Chinese population. However, chr6_32737733, a variant in HLA-DQB1, showed
      significant associations with both ER-negative and PR-negative breast cancer in
      the best fit to the dominant model. Furthermore, another significant correlation
      was seen between chr6_32606112, a variant in HLA-DRB5, and PR positivity. These
      results indicate that although no breast cancer risk variants in HLA class II
      were found in this Chinese population, HLA-DQB1 chr6_32737733 may be involved in
      determining a poor prognosis, whereas HLA-DRB5 chr6_32606112 may relate to a good
      prognosis.

PMID- 22393993
TI  - Decreasing trends of smoking and smoking cessation in successive Thai birth
      cohorts: age-period-cohort analysis from 1991-2007 national surveys.
AB  - BACKGROUND: Many tobacco control policies have been implemented to reduce tobacco
      use throughout the world including Thailand. This study made use of surveillance
      data of the past two decades to examine age- period-cohort effects on smoking in
      Thailand. METHODS: Six nationally representative datasets collected during 1991
      2007 were used to determine the prevalence of current smoking, former smoking,
      and never smoking. Effects of age-period-cohort on current, former, and never
      smoking were examined using age-period-cohort analysis. RESULTS: Overall tobacco
      consumption in Thailand has substantially decreased during the past two decades.
      However, a sluggish decline of smoking trend has been observed in the last
      decade. Age-period-cohort models showed significant effects of all three of these
      component factors on current smoking, former smoking, and never smoking, with the
      exception of an age effect only on former smoking in females. Age-specific
      prevalence of current smoking in successive birth cohorts increased with age
      towards 27 years in males and then fell with age while smoking cessation tended
      to increase with age. Newer cohorts tended to smoke less but were less likely to
      quit smoking than those in earlier cohorts. CONCLUSIONS: Although newer cohorts
      had less susceptibility to smoking, smokers in newer cohorts had lower odds of
      smoking cessation. Effective smoking cessation methods should be promoted.

PMID- 22393994
TI  - Clinical observation of Endostar(r) combined with chemotherapy in advanced
      colorectal cancer patients.
AB  - OBJECTIVE: Endostar(r) (Rh-endostatin injection) is a new recombinant human
      endostatin developed by Shandong Simcere-Medgenn Bio-Pharmaceutical Co., Ltd in
      China. This study was performed to evaluate the efficacy and safety of Endostar
      plus leucovorin calcium/ 5-fluorouracil/oxaliplatin (FOLFOX4) in treating
      patients with advanced colorectal cancer. METHODS: Thirty-six patients with
      advanced colorectal cancer were retrospectively assigned to one of two treatment
      groups: FOLFOX4 (control) or FOLFOX4 plus Endostar (Endostar) according to
      patient accreditation. The observational end points were overall response rate,
      overall survival, progression-free survival and toxicity. RESULTS: The response
      rate and progression-free survival of Endostar were significantly better than
      those of control group (P <0.05), but significance was not observed for median
      survival. In addition, gastrointestinal side effects and incidence of leucopenia
      were not lower than in the control group (P<0.05). CONCLUSIONS: The addition of
      Endostar to FOLFOX4 resulted in a higher objective response rate and longer time
      to disease progression. Hypertension and cardiac ischemia were the principal
      safety concerns, but were manageable. Endostar deserves to be further
      investigated by randomized controlled clinical trails.

PMID- 22393995
TI  - The NQO1 C609T polymorphism and risk of lung cancer: a meta-analysis.
AB  - OBJECTIVE: NAD(P)H: quinone oxidoreductase 1 (NQO1) is a cytosolic flavoprotein
      that catalyzes the two- electron reduction of quinoid compounds into
      hydroquinones. A single base substitution (C?T) polymorphism at 609 in the NQO1
      gene reduces quinone reductase activity. Published data on the association
      between NQO1 C609T polymorphism and lung cancer risk are conflicting. METHODS: To
      derive a more precise estimation of the relationship, a meta-analysis was
      performed. RESULTS: A total of 23 studies including 5,575 cases and 9,132
      controls were assessed. The pooled result showed that the NQO1 polymorphism was
      not associated with a clear increased risk of lung cancer (OR = 1.009, 95% CI:
      0.943-1.078; P heterogeneity=0.049). In the subgroup analysis by ethnicity, no
      clear increased risk was found among Asians for TT/CT versus CC (OR = 1.005; 95%
      CI = 0.890-1.135; P heterogeneity=0.024). However, the TT and CT genotypes
      combined were associated with significantly increased risk of lung cancer in
      Chinese (OR = 1.237, 95% CI: 1.029-1.486; P heterogeneity=0.061) among whom the
      variant allele is common. The variant genotype of NQO1 was also associated with
      modestly increased risk of lung cancer among white populations (OR = 1.017, 95%
      CI: 0.936-1.105; P heterogeneity=0.101). However, no significant association was
      found in Africans with all genetic models. CONCLUSIONS: Our meta-analysis
      suggests that the variant NQO1 C609T genotype may affect individual
      susceptibility to lung cancer. This meta- analysis suggests that the NQO1 609T
      allele is a low penetrant risk factor for developing lung cancer in Chinese.

PMID- 22393996
TI  - Polymorphisms in GSTM1, GSTTI and GSTP1 and nasopharyngeal cancer in the east of
      China: a case-control study.
AB  - AIM: The study was performed to assess the potential role of GSTM1, GSTT1 and
      GSTP1 polymorphisms in the risk of nasopharyngeal cancer in Chinese population.
      METHOD: We collected 182 cases undergoing pathologic examination and 366 controls
      from the affiliated hospital of Medical College of Qingdao University from April
      2006 to July 2010. Genotyping was based upon duplex polymerase-chain-reactions
      with the PCR- CTPP method. RESULTS: More smokers were found in NPC patients than
      controls, and a higher IgA/VCA+. Individuals carrying null GSTM1 and GSTT1 had
      1.76 and 2.01 fold risk of NPC when compared with non-null genotypes,
      respectively. A non-significant increase risk of NPC was found in individuals
      with 1b/1b genotype when compared with 1a/1a genotype (OR=1.32, 95%CI=0.60-2.94).
      When compared with non-null GSTM1 and GSTT1 genotypes, the combination of
      null/null GSTM1 and GSTT1 genotypes showed moderate increased risk of NPC
      (OR=3.03, 95% CI=1.74-5.08). CONCLUSION: Our study provides evidence that genetic
      deletion of GSTM1 and GSTT1 may contribute to increased susceptibility to NPC in
      Chinese population, while GSTP1 may not. Our findings provide information
      relevant to the prevention of NPC.

PMID- 22393997
TI  - High Ki-67 expression is a poor prognostic indicator of 5-year recurrence free
      survival in patients with invasive breast cancer.
AB  - OBJECTIVE: Ki-67 is a biomarker that reflects the cell proliferation state.
      Despite a clear understanding of the protein's structure and properties, its
      functional role remains elusive. We conducted the present study to assess the
      prognostic value of Ki-67 in breast cancer (BC). METHODS: We enrolled 164
      individuals in this study: 30 patients with benign tumors and 134 with invasive
      BC. Immunohistochemistry (IHC) was used to detect Ki-67 expression The prognostic
      value of Ki-67 for 5-year recurrence-free survival (RFS) could be analyzed in 134
      BC patients. RESULTS: Ki-67 expression showed significant differences with the
      tumor grade, lymph node (LN) status, HER2 status and hormone receptor (HR) status
      (all P<0.05). When Ki- 67 11% was used as cutoff to divide the 134 cases into two
      groups, with high and low expression, the patients in former had a significantly
      higher 5-year recurrence rate (37.1% vs 8.1%, P=0.001) and a worse RFS (log-rank
      test, P=0.0017) than those in low Ki-67 expression group. Ki-67 was an
      independent prognostic predictor of 5-year RFS in both univariate and
      multivariate analyses. CONCLUSIONS: Ki-67 can be used as a negative predictor of
      5-year RFS of patients with invasive BC.

PMID- 22393998
TI  - Genetic variation in the microRNA-499 gene and hepatocellular carcinoma risk in a
      Turkish population: lack of any association in a case-control study.
AB  - MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs with
      posttranscriptional regulatory functions as tumor suppressors and oncogenes. It
      has been suggested that the presence of single nucleotide polymorphisms (SNPs) in
      miRNAs can alter miRNA processing, expression, and/or binding to target mRNA and
      represent another type of genetic variability that can contribute to
      susceptibility to cancer development in humans. An adenine to guanine
      polymorphism (rs3746444), located in the sequence of miR-499, results in a change
      from A:U to G:U in its stem region. To determine the association of this
      polymorphism with the risk of hepatocellular carcinoma (HCC) in a Turkish
      population, a hospital-based case-control study was designed consisting of 222
      subjects with HCC and 222 cancer-free control subjects matched for age, gender,
      smoking and alcohol status. The genotype frequency of the miR-499 rs3746444
      polymorphism was determined using a polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) assay. No statistically significant
      differences were found in the allele or genotype distributions of the miR-499
      rs3746444 polymorphism among HCC and cancer-free control subjects (P>0.05). Our
      results demonstrate for the first time that the miR-499 rs3746444 polymorphism
      does not been any major role in genetic susceptibility to hepatocellular
      carcinogenesis, at least in the population studied here. Independent studies are
      need to validate our findings in a larger series, as well as in patients of
      different ethnic origins.

PMID- 22393999
TI  - Comparison of Aalen's additive and Cox proportional hazards models for breast
      cancer survival: analysis of population- based data from British Columbia,
      Canada.
AB  - BACKGROUND: Regression models for survival data have traditionally been based on
      the Cox regression model. However, its validity relies heavily on assumption of
      proportional hazards. Another restriction of the Cox model is insufficiency in
      dealing with time-varying covariate effects, since the regression coefficients
      are assumed constant. These weaknesses have generated interest in alternative
      approaches and with Aalen's additive model, the effect of the covariates acts on
      an absolute rather than a relative scale. We here fit the Cox and Aalen's
      additive models to breast cancer data for comparison through practical
      application. METHODS: The data related to 14,826 women diagnosed with breast
      cancer in BC during 1990-1999 and followed to 2010. Plots of the Martingale
      Residual Process and Arja's Plot was used to assess the fit of the additive
      model. The Cox-Snell residuals, Martingale residuals and scaled Schoenfeld
      residuals were used to check the Cox model. RESULTS: In the category of patients
      younger than 65 years the proportional hazard assumption was satisfied. In this
      category, by the Cox model, the variables "stage", "surgery", "radiotherapy",
      "chemotherapy", "hormone therapy" and interaction between "stage" and "surgery"
      proved significant. In the same category, by the Aalen's additive model, similar
      significant variables are selected except for "hormone therapy". The sign of
      estimated coefficients from survival functions based on the both Cox and Aalen's
      additive models were alike although estimated coefficients in the two models
      differed from the viewpoint of magnitude. In the category of patients older than
      65 years, the proportional hazard assumption was not satisfied, and the
      Stratified Cox model and Aalen's additive model gave similar results.
      CONCLUSIONS: Based on our findings, if the proportional hazard assumption is not
      satisfied, the Aalen's additive model is an appropriate alternative for the Cox
      model. If the proportional hazard assumption is satisfied, both models are
      appropriate. Generally, the two models give different pieces of information.

PMID- 22394000
TI  - Family history of cancer and risk of gastric cancer in Iran.
AB  - INTRODUCTION: Gastric cancer is one of the major causes of cancer related death
      in the world. A number of risk factors are now known to be related to the
      development of the disease. Previous reports indicated that a family history is a
      serious risk, but there is a little information about this in Iran. The aim of
      this study was to explore the relation between family history of cancer in first
      and second degree relatives and the risk of GC in Iran. METHODS: The present
      study was designed as unmatched case control study. Cases were 746 patients with
      histologically confirmed GC and the 746 controls were randomly selected among the
      healthy participants in a health survey. Family history was extracted from a
      standard history form completed by the patient or from records created by a
      health care provider. Mantel-Heanszel odds ratios were computed for removing the
      confounding effect of age and sex. RESULTS: Overall, 9.7% of cases versus 5.6% of
      controls reported a family history of GC. Risk increased over twofold for this
      group. There was no significant association among family history of other cancers
      and GC (P>0.05). CONCLUSION: In conclusion, this study showed that family history
      of GC, especially in first-degree relatives, increases the risk of development of
      the disease. Further studies are needed to better understand the roles of genetic
      and environmental factors and their interaction in gastric cancer development in
      the Iranian community.

PMID- 22394001
TI  - Quality of life in women with gynecologic cancer in Turkey.
AB  - AIM: The management of gynecological cancer patients mainly aims at prolonging
      survival but modern therapy focuses on good survival combined with a good quality
      of life (QoL). The aim of this study was to evaluate QoL and identify its
      associated factors in Turkish women with gynecologic cancer. METHOD: The study
      included 119 women diagnosed with endometrial, cervical, ovarian or vulvar cancer
      and treated at the Gynecologic Oncology Department of Celal Bayar University
      Faculty of Medicine. The data were collected between January and June 2011. QoL
      was measured with EORTC QLQ-C30 version 3.0. Relationships between clinical and
      socio- demographic characteristics and QoL scores were analyzed using the Mann
      Whitney U, Kruskal Wallis and t-tests. RESULT: Global health status, physical and
      role function scores were found higher in women under the age of 60 years. Role
      function scores were found lower, and emotional and social scores were found to
      be higher in single women than in married women. Physical scores were found
      higher in women who had graduated from secondary school or above. Women with
      ovarian cancer had the highest while women with cervical cancer had the lowest
      global health score (65.3 +/- 24.7 and 43.0 +/- 24.1, respectively). Women with
      endometrial cancer were found to have better role function, and social well being
      than those with vulvar, cervical or ovarian cancer. Global, physical, role
      function, cognitive and social scores were found higher in women who had been
      treated with surgery. CONCLUSION: Gynecological cancer and treatment processes
      cause significant problems that have negative effects on physical, emotional,
      social and role function aspects of QoL. Health care providers play a key role in
      the identification and treatment of the complications of cancer therapy.
      Minimizing the effect of the symptoms of gynecologic cancer may positively impact
      on patient QoL.

PMID- 22394002
TI  - Breast cancer research in Iran; essential data to organize research.
AB  - BACKGROUND: Considering that breast cancer is one of the most burdensome diseases
      our societies are facing, and given our lack of knowledge in the research field
      of the important disease, it is essential that we strategize research policies by
      identifying defects in research systems in each country. The goal of this study
      was to explore the published articles in this field and present the data required
      for the policy makers to re-organize the breast cancer research in Iran. METHODS:
      In this descriptive study, Pubmed searches were performed to find all the
      articles published on the title of breast "cancer", "tumor", "malignancy" and
      "Iran" from the beginning up to the end of January 2010. Different research
      categories of the articles were defined and validated by an expert panel. The
      abstracts of all 180 articles were reviewed and each article was put into the
      relevant category. RESULTS: Based on the available evidence the majority of
      articles have focused on molecular science (21%) and genetics (19%), while the
      remainder belonged to other categories like quality of life (9%), screening
      protocols (8%), epidemiology (7%), risk factor studies (6%), pathology (6%),
      patient knowledge and behavior (5%) and other clinical research fields (19%). The
      most used methodologies are cross-sectional (39%) and case-control (25%). The
      other articles are designed in formats such as experimental (8%), cohort (6%),
      case-report (6%), review article (4%) and others methodologies (12%). CONCLUSION:
      Despite the increasing body of literature under the title of breast cancer since
      2000 from Iran, still there are limited published articles in some important
      categories with strong levels of evidence of relevance, which calls for extra
      efforts to reassess the research system policies and budgeting standards.

PMID- 22394003
TI  - Closing the disparity gap: cancer screening interventions among Asians--a
      systematic literature review.
AB  - BACKGROUND: Cancer is a leading cause of deaths among Asian Americans. However,
      the rates of screening among Asian Americans are low. The use of effective
      culturally-appropriate interventions needs to be explored. METHODS: Electronic
      databases were searched for articles published between January 1995 and December
      2010 for a comprehensive literature review. Interventions to increase breast,
      cervical and colorectal cancer screening among Asians populations in the US and
      overseas were included. RESULTS: A total of thirty studies were reviewed. These
      studies differed on study design, target population, theoretical underpinning of
      intervention approach and outcome measures. Effective interventions employed a
      variety of strategies including the use of social networks, lay health workers,
      media education, community-based education, reminder notices, health care
      provider assistance and health system changes. Fifteen studies utilized
      behavioral theories in intervention development. CONCLUSIONS: This review finds
      culturally-appropriate community-based interventions and lay health worker
      strategies can improve cancer screening behaviors among Asian populations.
      Selections of intervention strategies will depend on the characteristics of the
      target group and feasibility of implementation. Challenges and recommendations
      for tailored screening interventions for Asians are discussed.

PMID- 22394004
TI  - MDR1 gene polymorphisms: possible association with its expression and
      clinicopathology characteristics in colorectal cancer patients.
AB  - AIM: Over-expression of some genes, such as MDR1, can increase the level of
      chemotherapy drug afflux and limit the effectiveness of treatment. We aimed to
      investigate the effect of MDR1 polymorphisms on its expression level and related
      characteristics in Iranian colorectal cancer patients. METHODS: Tumor, normal
      mucosal tissue and blood samples from CRC patients and blood samples from healthy
      controls (n=60) were obtained for genotyping and measuring the expression level
      of MDR1. RESULTS: The expression of the MDR1 gene showed a significant increase
      in cancerous regions compared to adjacent normal tissue. Furthermore, the GG2677
      genotype was correlated with highest while the AT 2677 genotype was associated
      with the lowest levels of expression. In addition only the G2677T/A polymorphism
      showed association with histological grade of colorectal tumors. CONCLUSION: Our
      study once more emphasizes effects of MDR1 SNPs which may indirectly impact on
      response to drugs.

PMID- 22394006
TI  - Exploration of cancer pain treatment by morphine infusion through an embedded
      device.
AB  - Cancer pain treatment with morphine presents particular problems in patients with
      renal failure needing haemodialysis. We here explore the various possibilities of
      intrathecal opioid administration for intractable chronic and acute cancer pain.
      Morphine, as the only opioid approved by the Food and Drug Agency for
      administration, has been increasingly utilized for this purpose. For over 3
      decades, there have been numerous reports on non- nociceptive side effects
      associated with ever increasing long-term intrathecal morphine usage. Our review
      of the literature and our own experience suggests that a subarachnoid device
      allows good pain control effect after patient controlled intravenous infusion
      failure at the time of haemodialysis.

PMID- 22394005
TI  - Tumor markers and biochemical parameters in colon cancer patients before and
      after chemotherapy.
AB  - OBJECTIVES: Tumor markers and biochemical parameters were investigated in
      patients suffering from colon cancer and in volunteer healthy persons. DESIGN AND
      METHODS: Biochemical analyses of erythrocyte enzymes and serum values for series
      of established tumor markers were conducted for 40 patients diagnosed with colon
      cancer, before and after chemotherapy, and 29 healthy volunteers between 2008 and
      2009. RESULTS: Activities of catalase and carbonic anhydrase were lower in sick
      than healthy groups (p<0.05) before and after chemotherapy, while alkaline
      phosphatase and creatinine were increased. The patients with colon cancer showed
      significant (p<0.05) elevation of CRP, fibrinogen, CA125, AFP, and decrease in
      ferritinin, before but not after therapy. CONCLUSION: The results obtaining from
      this investigation can be useful for colon cancer risk assessment.

PMID- 22394007
TI  - Understanding decision and enabling factors influencing clinical trial
      participation in Australia: a view point.
AB  - Understanding patient decision making with respect to clinical trial
      participation has the potential to improve both the efficiency of recruitment for
      clinical trials and their management. In this mini-review we consider 3 key
      factors influencing clinical trial recruitment outcomes that include; 1) patient
      personal characteristics, 2) enabling factors that involve patient centered
      attitudes or circumstances, and 3) aversion. These factors are explored across
      both Australian rural and urban settings and contrasted to reported outcomes from
      research across other countries. Australia has the lowest number of publications
      on rural clinical trial participation when compared to rural research in America
      and Canada. Across Australian urban areas where all 3 factors have been studied,
      trends are similar to those reported in other developed countries. In conclusion
      we suggest that trial participation could be improved if participants are better
      informed about a trial as this is a valuable factor to enable recruitment.

PMID- 22394008
TI  - Association of COX-2 8473T>C gene polymorphism with lung cancer risk.

PMID- 22394009
TI  - Novel anti-acne actions of nadifloxacin and clindamycin that inhibit the
      production of sebum, prostaglandin E(2)  and promatrix metalloproteinase-2 in
      hamster sebocytes.
AB  - Acne vulgaris is characteristic of excess sebum production and the induction of
      inflammatory reactions, for example, the augmentation of cytokine, prostaglandin
      (PG) and matrix metalloproteinase (MMP) production in sebaceous glands and
      pilosebaceous units. As Propionibacterium acnes is considered to be involved in
      the aggravation of acne vulgaris, antimicrobial agents have been found to be
      effective for treating acne leading to the remission of inflammation. However, it
      is not fully understood whether antimicrobial agents influence sebum production
      and/or the inflammatory reactions in sebaceous gland cells (sebocytes). In the
      present study, topical antimicrobial agents such as nadifloxacin (NDFX) and
      clindamycin (CLDM) decreased the production of triacylglycerols (TG), which are a
      major component of sebum in insulin-differentiated hamster sebocytes. These
      antibiotics also suppressed insulin-augmented gene expression and the production
      of perilipin, by which intracellular lipid droplet formation was concomitantly
      inhibited. On the other hand, peptidoglycan (PGN) from Gram-positive bacteria
      dose-dependently increased TG production in hamster sebocytes. The augmented TG
      production was decreased by treating NDFX or CLDM. Furthermore, NDFX and CLDM
      inhibited the PGN-augmented PGE(2)  production in the sebocytes. Moreover, NDFX,
      but not CLDM, suppressed the PGN-augmented gene expression and production of pro
      MMP-2/progelatinase A in hamster sebocytes. Therefore, these results provide
      novel evidence that NDFX and CLDM exhibit anti-lipogenesis and anti-inflammatory
      activities against insulin- or PGN-activated sebocytes which at least partly
      mimic acne pathology in vitro. Moreover, NDFX for acne therapy is likely to be
      effective in not only inhibiting microbial proliferation but also in preventing
      the onset of acne scar formation.

PMID- 22394011
TI  - Case-study magnetic resonance imaging and acoustic investigation of the effects
      of vocal warm-up on two voice professionals.
AB  - Vocal warm-up (WU)-related changes were studied in one male musical singer and
      one female speech trainer. They sustained vowels before and after WU in a
      magnetic resonance imaging (MRI) device. Acoustic recordings were made in a
      studio. The vocal tract area increased after WU, a formant cluster appeared
      between 2 and 4.5 kHz, and SPL increased. Evidence of larynx lowering was only
      found for the male. The pharyngeal inlet over the epilaryngeal outlet ratio
      (A(ph)/A(e)) increased by 10%-28%, being 3-4 for the male and 5-7 for the female.
      The results seem to represent different voice training traditions. A singer's
      formant cluster may be achievable without a high A(ph)/A(e) (>= 6), but
      limitations of the 2D method should be taken into account.

PMID- 22394010
TI  - Erk2 in ovarian development of green mud crab Scylla paramamosain.
AB  - We identified extracellular signal-regulated kinase 2 (erk2) from green mud crab,
      Scylla paramamosain, in this article. It was originally identified from an
      expressed sequence tag fragment from a normalized gonadal cDNA library. 5' Rapid
      amplification of cDNA end (RACE) technique was used to obtain the 5' untranslated
      region (UTR). The full-length cDNA of Sp-erk2 is 1516 bp, including a 5'-terminal
      UTR of 19 bp, an open-reading frame of 1098 bp, and a 3'-terminal UTR of 399 bp.
      The translated protein is 365 amino acids in length with a predicted molecular
      weight of 42 kDa, which is the same as other species. It is the first time that
      the expression of Sp-erk2 in different stages of ovary development of crustacean
      was analyzed, and the result showed that the expression of Sp-erk2 increased
      gradually with ovarian development, with a peak in the mature phase. In situ
      hybridization histochemistry was used to clarify the detail of expression.
      Positive signals illustrated that Sp-erk2 mRNA is present in follicular cells
      when the ovary is in early stages, and in both follicular cells and oocytes when
      it is in mature phases. All above suggest that Sp-erk2 is important for ovarian
      development.

PMID- 22394012
TI  - Tissue microarray and digital image analysis: a methodological study with special
      reference to the microenvironment in Hodgkin lymphoma.
AB  - AIM: Cancer research has moved from solely investigating the tumour cells to also
      including analysis of the tumour microenvironment; however, the methods utilized
      have not been evaluated for this change. The aim of this study was to compare
      tissue microarrays (TMA) to whole tissue sections (WS) with regard to cells in
      the tumour microenvironment. Manual evaluation and digital image analyses (DIA)
      were utilized and also compared. METHODS AND RESULTS: TMA slides from 117 Hodgkin
      lymphoma patients were immunostained for forkhead box protein 3 (FoxP3)
      [identifying regulatory T cells (T(reg) )], and 39 corresponding WS were also
      analysed. Manual evaluation and DIA were utilized for all patients on both the
      TMA and the WS. A correlation coefficient of 0.83 was obtained for the proportion
      of T(reg) in TMA versus WS using manual evaluation and a correlation coefficient
      of 0.77 with DIA. T(reg) counts using manual evaluation correlated in turn with
      DIA, with a coefficient of 0.79 for the 117 TMA sections and 0.65 for the 39 WS.
      CONCLUSION: Because a high correlation was observed between TMA and WS, TMA can
      be utilized when evaluating cells in the tumour microenvironment. DIA appears to
      provide a reliable measurement method, provided that manual control of the tumour
      slides is conducted.

PMID- 22394013
TI  - Asymmetric synthesis of (triaryl)methylamines by rhodium-catalyzed addition of
      arylboroxines to cyclic N-sulfonyl ketimines.
AB  - Asymmetric addition of arylboroxines to cyclic N-sulfonyl ketimines proceeded in
      the presence of a rhodium catalyst coordinated with a chiral diene ligand to give
      high yields of benzosultams, where a triaryl-substituted stereogenic carbon
      center was created with high enantioselectivity (93-99% ee). The chiral
      benzosultams were transformed into the chiral (triaryl)methylamines by breaking
      the cyclic structure.

PMID- 22394014
TI  - Causal implication by rhythmic transcranial magnetic stimulation of alpha
      frequency in feature-based local vs. global attention.
AB  - Although oscillatory activity in the alpha band was traditionally associated with
      lack of alertness, more recent work has linked it to specific cognitive
      functions, including visual attention. The emerging method of rhythmic
      transcranial magnetic stimulation (TMS) allows causal interventional tests for
      the online impact on performance of TMS administered in short bursts at a
      particular frequency. TMS bursts at 10 Hz have recently been shown to have an
      impact on spatial visual attention, but any role in featural attention remains
      unclear. Here we used rhythmic TMS at 10 Hz to assess the impact on attending to
      global or local components of a hierarchical Navon-like stimulus (D. Navon (1977)
      Forest before trees: The precedence of global features in visual perception.
      Cognit. Psychol., 9, 353), in a paradigm recently used with TMS at other
      frequencies (V. Romei, J. Driver, P.G. Schyns & G. Thut. (2011) Rhythmic TMS over
      parietal cortex links distinct brain frequencies to global versus local visual
      processing. Curr. Biol., 2, 334-337). In separate groups, left or right posterior
      parietal sites were stimulated at 10 Hz just before presentation of the
      hierarchical stimulus. Participants had to identify either the local or global
      component in separate blocks. Right parietal 10 Hz stimulation (vs. sham)
      significantly impaired global processing without affecting local processing,
      while left parietal 10 Hz stimulation vs. sham impaired local processing with a
      minor trend to enhance global processing. These 10 Hz outcomes differed
      significantly from stimulation at other frequencies (i.e. 5 or 20 Hz) over the
      same site in other recent work with the same paradigm. These dissociations
      confirm differential roles of the two hemispheres in local vs. global processing,
      and reveal a frequency-specific role for stimulation in the alpha band for
      regulating feature-based visual attention.

PMID- 22394015
TI  - Side-on bound complexes of phenyl- and methyl-diazene.
AB  - Treatment of trans-[FeCl(2)(dmpe)(2)] with phenylhydrazine and 1 equiv of base
      afforded the side-on bound phenylhydrazido complex cis-[Fe(eta(2)
      NH(2)NPh)(dmpe)(2)](+). Further deprotonation of the phenylhydrazido complex
      afforded the side-on bound phenyldiazene complex cis-[Fe(eta(2)-HN?NPh)(dmpe)(2)]
      as a mixture of diastereomers. Treatment of cis-[RuCl(2)(dmpe)(2)] with
      phenylhydrazine or methylhydrazine afforded the end-on bound phenylhydrazine or
      methylhydrazine complexes cis-[RuCl(eta(1)-NH(2)NHR)(dmpe)(2)](+) (R = Ph, Me).
      Treatment of the substituted hydrazine complexes with base afforded the side-on
      bound phenylhydrazido complex cis-[Ru(eta(2)-NH(2)NPh)(dmpe)(2)](+) as well as
      the phenyldiazene and methyldiazene complexes cis-[Ru(eta(2)-HN?NR)(dmpe)(2)] (R
      = Ph, Me). cis-[RuCl(eta(1)-NH(2)NHR)(dmpe)(2)](+) (R = Ph, Me), cis-[M(eta(2)
      NH(2)NPh)(dmpe)(2)](+) (M = Fe, Ru) and cis-[Ru(eta(2)-HN?NPh)(dmpe)(2)] were
      characterized structurally by X-ray crystallography. cis-[Ru(eta(2)
      HN?NPh)(dmpe)(2)] is the first side-on bound phenyldiazene complex to be
      structurally characterized. In the structure of cis-[Ru(eta(2)-HN?NPh)(dmpe)(2)],
      the geometry of the coordinated diazene fragment is significantly nonplanar (CNNH
      angle 137 degrees ) suggesting that the complex is probably better described as a
      Ru(II) metallodiaziridine than a Ru(0) diazene pi-complex.

PMID- 22394016
TI  - Health system barriers to implementation of collaborative TB and HIV activities
      including prevention of mother to child transmission in South Africa.
AB  - In South Africa, the control of TB and HIV co-infection remains a major challenge
      despite the availability of international and national guidelines for integration
      of TB and HIV services. This study was undertaken in KwaZulu-Natal, one of the
      provinces most affected by both TB and HIV, to identify and understand managers'
      and community care workers' (CCWs) perceptions of health systems barriers related
      to the implementation of collaborative TB/HIV activities, including prevention of
      mother to child transmission of HIV (PMTCT). We conducted 29 in-depth interviews
      with health managers at provincial, district and facility level and with managers
      of NGOs involved in TB and HIV care, as well as six focus group discussions with
      CCWs. Thematic analysis of transcripts revealed a convergence of perspectives on
      the process and the level of the implementation of policy directives on
      collaborative TB and HIV activities across all categories of respondents (i.e.
      province-, district-, facility- and community-based organizations). The majority
      of participants felt that the implementation of the policy was insufficiently
      consultative and that leadership and political will were lacking. The predominant
      themes related to health systems barriers include challenges related to structure
      and organisational culture; management, planning and power issues; unequal
      financing; and human resource capacity and regulatory problems notably relating
      to scope of practice of nurses and CCWs. Accelerated implementation of
      collaborative TB/HIV activities including PMTCT will require political will and
      leadership to address these health systems barriers.

PMID- 22394017
TI  - Direct human cartilage repair using three-dimensional bioprinting technology.
AB  - Current cartilage tissue engineering strategies cannot as yet fabricate new
      tissue that is indistinguishable from native cartilage with respect to zonal
      organization, extracellular matrix composition, and mechanical properties.
      Integration of implants with surrounding native tissues is crucial for long-term
      stability and enhanced functionality. In this study, we developed a bioprinting
      system with simultaneous photopolymerization capable for three-dimensional (3D)
      cartilage tissue engineering. Poly(ethylene glycol) dimethacrylate (PEGDMA) with
      human chondrocytes were printed to repair defects in osteochondral plugs (3D
      biopaper) in layer-by-layer assembly. Compressive modulus of printed PEGDMA was
      395.73+/-80.40 kPa, which was close to the range of the properties of native
      human articular cartilage. Printed human chondrocytes maintained the initially
      deposited positions due to simultaneous photopolymerization of surrounded
      biomaterial scaffold, which is ideal in precise cell distribution for anatomic
      cartilage engineering. Viability of printed human chondrocytes increased 26% in
      simultaneous polymerization than polymerized after printing. Printed cartilage
      implant attached firmly with surrounding tissue and greater proteoglycan
      deposition was observed at the interface of implant and native cartilage in
      Safranin-O staining. This is consistent with the enhanced interface failure
      strength during the culture assessed by push-out testing. Printed cartilage in 3D
      biopaper had elevated glycosaminoglycan (GAG) content comparing to that without
      biopaper when normalized to DNA. These observations were consistent with gene
      expression results. This study indicates the importance of direct cartilage
      repair and promising anatomic cartilage engineering using 3D bioprinting
      technology.

PMID- 22394018
TI  - Wechsler Adult Intelligence Scale-Fourth Edition performance in relapsing
      remitting multiple sclerosis.
AB  - Forty patients with relapsing-remitting multiple sclerosis (MS) completed the 10
      core Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) subtests. Means
      for age and education were 42.05 years (SD = 9.94) and 14.33 years (SD = 2.40).
      For all participants, the native language was English. The mean duration of MS
      diagnosis was 8.17 years (SD = 7.75), and the mean Expanded Disability Status
      Scale (EDSS; Kurtzke, 1983 ) score was 3.73 (SD = 1.41) with a range from 2.0 to
      6.5. A control group of healthy individuals with similar demographic
      characteristics also completed the WAIS-IV and were provided by the test
      publisher. Compared to controls, patients with MS earned significantly lower
      subtest and composite scores. The patients' mean scores were consistently in the
      low-average to average range, and the patterns of performance across groups did
      not differ significantly, although there was a trend towards higher scores on the
      Verbal Comprehension Index (VCI) and lower scores on the Processing Speed Index
      (PSI). Approximately 78% of patients had actual Full Scale IQs that were
      significantly lower than preillness, demographically based IQ estimates.

PMID- 22394019
TI  - Obtaining an isolate of Ancylostoma braziliense from cats without the need for
      necropsy.
AB  - Because the eggs of Ancylostoma species of dogs and cats are difficult to readily
      distinguish morphologically, isolation of a certain species often requires the
      humane death of the source animal or holding an animal after treatment to obtain
      worms for specific identification or to harvest ex utero eggs. The objective of
      this study was to obtain an isolate of Ancylostoma braziliense from 1-time, field
      collected samples of feline feces without the need for the killing of any
      animals. During a collection trip to Florida, fecal samples (n  =  40) were
      collected and identified as containing A. braziliense eggs (n  =  26) using
      centrifugal sugar flotation. Eggs from hookworm-positive slides were washed into
      tubes, DNA was extracted, and 10 samples were identified as containing A.
      braziliense using restriction fragment length polymorphism (RFLP) with Hinf1. Six
      of these samples also contained DNA of Ancylostoma tubaeforme and, thus, only 4
      samples were from cats infected only with A. braziliense. Larvae cultured from
      two of the latter samples were used to subcutaneously inoculate a purpose-bred
      puppy with the intention to inhibit the growth of any potentially contaminating
      A. tubaeforme larvae in the culture. The infection was patent at 14 days after
      inoculation, and the eggs were identified as A. braziliense by RFLP and DNA
      sequencing. Larvae were cultured from the feces of this dog and used to infect a
      laboratory-reared, specific-pathogen-free cat; the eggs and larvae produced by
      the cat were also identified molecularly as those of A. braziliense. The larvae
      from this cat were used to infect other cats to maintain the isolate for further
      research. Both the puppy and the first cat used in this study were treated to
      clear their infections and have since been adopted by new owners.

PMID- 22394020
TI  - Volatile aroma components and antioxidant activities of the flavedo peel extract
      of unripe Shiikuwasha (Citrus depressa Hayata).
AB  - The flavedo peel extracts of unripe Shiikuwasha (Citrus depressa Hayata) fruits
      were extracted using steam distillation (SD) or a cold-press (CP) system.
      Volatile aroma content and composition were determined using gas chromatography
      (GC) and each compound was identified using gas chromatography-mass
      spectrophotometry (GC-MS). The major constituents of the extracts were
      monoterpene hydrocarbons (91.75-93.75%[709.32-809.05 mg/100 g of fresh flavedo
      peel]) including limonene (43.08-45.13%[341.46-379.81 mg/100 g of fresh flavedo
      peel]), gamma-terpinene (27.88-29.06%[219.90-245.86 mg/100 g of fresh flavedo
      peel]), and p-cymene (8.13-11.02%[61.47-97.22 mg/100 g of fresh flavedo peel]).
      The extraction process used was determined to be a decisive factor that affects
      the composition of key citrus aroma components, as well as the antioxidant
      activities of the Shiikuwasha fruit. Antioxidant capabilities of the extracts
      were examined by assay of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging
      activity and beta-carotene bleaching inhibition. The cold-press extraction system
      may better retain the total phenolic content of the flavedo peel and display
      superior antioxidant activities, compared to the steam distillation extraction
      method. PRACTICAL APPLICATION: Shiikuwasha (Citrus depressa Hayata) is a type of
      small citrus fruit, and has been used as raw material for beverage and food
      additive productions in Japan. It had a unique aroma composition in which the
      limonene content of its peels is lower than that of other commonly known citrus
      peels. The present study detailed the volatile aroma composition, as well as
      antioxidant capabilities of Shiikuwasha peel extracts of different extraction
      methods, that are cold-press and steam distillation methods. The results of this
      study may provide a basis for selection of Shiikuwasha peel extracts in food
      industry for citrus flavor production.

PMID- 22394021
TI  - Nutrition and kidney in preterm infant.
AB  - In pre- and post-natal period nutrition can influence the function of many
      organs, including the kidneys. Intrauterine growth restriction and low weight at
      birth are associated with reduced nephron number, a risk factor for later
      cardiovascular and renal diseases. The development of such adult diseases may be
      favored, in animals, by additional risk factors, including postnatal
      overnutrition and/or rapid postnatal growth. In preterm infants, during the first
      weeks of life, high values of serum urea are presents due to immaturity of the
      renal function. Thus the urea cannot be used in the first weeks of life as a
      parameter to evaluate the adequacy of protein intake. In comparison with older
      infants, healthy preterm infants, fed on human milk and adapted formulas, show a
      lower renal solute load because the higher growth rate associated with a raised
      nitrogen and mineral retention rate. Preterm infants are vulnerable to
      disturbances of acid-base metabolism, with a predisposition to metabolic acidosis
      due to a transient age-related low renal capacity for net acid excretion.

PMID- 22394022
TI  - Nuclear factor kappaB-dependent anti-inflammatory effects of s-allyl cysteine and
      s-propyl cysteine in kidney of diabetic mice.
AB  - Renal protection of s-allyl cysteine (SAC) and s-propyl cysteine (SPC) in
      diabetic mice against inflammatory injury was examined. Each agent at 0.5 and 1
      g/L was added to the drinking water for 10 weeks. SAC or SPC intake significantly
      reduced the plasma blood urea nitrogen level and increased creatinine clearance
      (P < 0.05). These treatments significantly lowered the renal level of reactive
      oxygen species, nitric oxide, interleukin-6, tumor necrosis factor-alpha, and
      prostaglandin E(2) in diabetic mice (P < 0.05). Renal mRNA expression of
      inducible nitric oxide synthase, cyclooxygenase-2, protein kinase C (PKC)-alpha,
      PKC-beta, and PKC-gamma was enhanced in diabetic mice (P < 0.05); however, SAC or
      SPC treatments dose dependently declined mRNA expression of these factors (P <
      0.05). Nuclear factor kappaB (NF-kappaB) activity, mRNA expression, and protein
      production in kidney of diabetic mice were significantly increased (P < 0.05).
      SAC or SPC intake dose dependently suppressed NF-kappaB activity, NF-kappaB p65
      mRNA expression, and protein level (P < 0.05). Diabetes also enhanced renal
      protein expression of mitogen-activated protein kinase (P < 0.05). SAC and SPC,
      only at a high dose, significantly suppressed protein production of p-p38 and p
      ERK1/2 (P < 0.05). Renal mRNA expression and protein generation of peroxisome
      proliferator-activated receptor (PPAR)-alpha and PPAR-gamma were significantly
      down-regulated in diabetic mice (P < 0.05), but the intake of SAC or SPC at high
      dose up-regulated PPAR-alpha and PPAR-gamma (P < 0.05). These findings support
      that SAC and SPC are potent anti-inflammatory agents against diabetic kidney
      diseases.

PMID- 22394023
TI  - Effect of airborne-particle abrasion and aqueous storage on flexural properties
      of fiber-reinforced dowels.
AB  - PURPOSE: A great range of clinical failures have been observed with fiber
      reinforced dowels, often attributed to fracture or bending of the dowels. This
      study investigated flexural properties of fiber-reinforced dowels, with and
      without airborne-particle abrasion, after storage in aqueous environments over
      time. Scanning electron microscopy (SEM) was used to analyze the mode of failure
      of dowels. MATERIALS AND METHODS: Two dowel systems (ParaPost Fiber Lux and
      FibreKor) were evaluated. Ten dowels of each system were randomly assigned to one
      of six experimental groups: 1--control, dry condition; 2--dowels airborne
      particle abraded and then stored dry; 3--dowels stored for 24 hours in aqueous
      solution at 37 degrees C; 4--dowels airborne-particle abraded followed by 24-hour
      aqueous storage at 37 degrees C; 5--dowels stored for 30 days in aqueous solution
      at 37 degrees C; 6--dowels airborne-particle abraded followed by 30-day aqueous
      storage at 37 degrees C. Flexural strength and flexural modulus were tested for
      all groups according to American Society of Testing and Materials (ASTM) standard
      D4476. One failed dowel from each group was randomly selected to be evaluated
      with SEM equipped with energy dispersive spectroscopy (EDS) to characterize the
      failure pattern. One intact dowel of each system was also analyzed with SEM and
      EDS for baseline information. RESULTS: Mean flexural modulus and strength of
      ParaPost Fiber Lux dowels across all conditions were 29.59 +/- 2.89 GPa and
      789.11 +/- 89.88 MPa, respectively. Mean flexural modulus and strength of
      FibreKor dowels across all conditions were 25.58 +/- 1.48 GPa and 742.68 +/-
      89.81 MPa, respectively. One-way ANOVA and a post hoc Dunnett's t-test showed a
      statistically significant decrease in flexural strength as compared to the dry
      control group for all experimental groups stored in water, for both dowel systems
      (p < 0.05). Flexural modulus for both dowel systems showed a statistically
      significant decrease only for dowels stored in aqueous solutions for 30 days (p <
      0.05). Airborne-particle abrasion did not have an effect on flexural properties
      for either dowel system (p > 0.05). SEM and EDS analyses revealed differences in
      composition and failure mode of the two dowel systems. Failed dowels of each
      system revealed similar failure patterns, irrespective of the experimental group.
      CONCLUSIONS: Aqueous storage had a negative effect on flexural properties of
      fiber-reinforced dowels, and this negative effect appeared to increase with
      longer storage times. The fiber/resin matrix interface was the weak structure for
      the dowel systems tested.

PMID- 22394024
TI  - Salmonella population rebound and its prevention on spray washed and non-washed
      jalapeno peppers and roma tomatoes in humid storage.
AB  - The potential of Salmonella population to rebound on non-washed and washed roma
      tomatoes and jalapeno peppers in humid storage at 4 degrees C, 10 degrees C, 15
      degrees C, 21 degrees C, or 35 degrees C for <=12 days was investigated. The
      initial inoculation levels of Salmonella on peppers and tomatoes were 5.6 and 5.2
      log CFU/cm(2), respectively. Air-drying of fruit surfaces resulted in
      contamination levels of 3.9 and 3.7 log CFU/cm(2) on inoculated peppers and
      tomatoes, respectively. At 21 degrees C and 35 degrees C, the levels of air-dried
      Salmonella inoculums on produce surfaces increased >=2 log cycles, with the most
      rapid growth in the first 3 days. Mechanical washing on rollers (rinsing; R
      treatment) or revolving brushes (rinsing and brushing; RB-treatment) with water
      decreased Salmonella counts by >=2.5 log CFU/cm(2) on both peppers and tomatoes.
      After R- or RB-treatment, peppers stored at 21 degrees C and 35 degrees C
      permitted residual Salmonella (<=1.4 log CFU/cm(2)) to grow to 2.6-3.9 log
      CFU/cm(2). During storage, residual Salmonella (<=1.0 log CFU/cm(2)) on washed
      tomatoes increased to 3.1 log CFU/cm(2) at 35 degrees C following R-treatment and
      3.8 log CFU/cm(2) at 21 degrees C following RB-treatment. Cold storage at 4
      degrees C and 10 degrees C effectively prevented the proliferation of Salmonella
      on both washed and non-washed produce. The current study on jalapeno peppers and
      roma tomatoes demonstrated that Salmonella population can rebound on produce in
      humid storage before or after washing. The finding highlights the benefit of
      uninterrupted cold storage for safer produce operations.

PMID- 22394025
TI  - Enhanced inhibition of Listeria monocytogenes by a combination of cold pressed
      terpeneless Valencia orange oil and antibiotics.
AB  - This study was designed to evaluate the ability of cold pressed terpeneless
      Valencia orange oil (CPTVO) to enhance the effectiveness of antibiotics against
      10 strains of Listeria monocytogenes. Disc diffusion assays were performed to
      determine the effects of CPTVO and two antibiotics with different mechanisms of
      action (i.e., penicillin and chloramphenicol) individually and in combination
      with CPTVO. CPTVO alone produced zones ranging from 16.5 to 19.9 mm. Penicillin
      at 2 or 10 units produced zones ranging from <6 to 13.4 mm, and from 16 to 19.5
      mm, respectively. Chloramphenicol at 5 or 30 MUg had zones ranging from <6 to 6.9
      mm, and from 10.8 to 15.9 mm, respectively. Penicillin (2 and 10 units) plus
      CPTVO produced zones ranging from 20.2 to 25.3 mm, and from 21.9 to 28 mm,
      respectively. Chloramphenicol (5 or 30 MUg) plus CPTVO produced zones of from
      20.1 to 26.6 mm, and from 19.5 to 23.9 mm, respectively. In conclusion, the
      combination of antibiotics with CPTVO increases their ability to inhibit L.
      monocytogenes.

PMID- 22394026
TI  - Ultrastructure of ubiquitin-positive, TDP-43-negative neuronal inclusions in
      cerebral cortex of C9ORF72-linked frontotemporal lobar degeneration/amyotrophic
      lateral sclerosis.

PMID- 22394028
TI  - Neutrophilic dermatosis of the palms.

PMID- 22394027
TI  - Intraspecific genotypic variability determines concentrations of key truffle
      volatiles.
AB  - * Aroma variability in truffles has been attributed to maturation (Tuber
      borchii), linked to environmental factors (Tuber magnatum), but the involvement
      of genetic factors has been ignored. We investigated aroma variability in Tuber
      uncinatum, a species with wide distribution. Our aim was to assess aroma
      variability at different spatial scales (i.e. trees, countries) and to quantify
      how aroma was affected by genotype, fruiting body maturity, and geographical
      origin. * A volatile fingerprinting method was used to analyze the aroma of 223
      T. uncinatum fruiting bodies from seven European countries. Maturity was
      estimated from spore melanization. Genotypic fingerprinting was performed by
      amplified fragment length polymorphism (AFLP). * Discriminant analysis revealed
      that, regardless of the geographical origin of the truffles, most of the aroma
      variability was caused by eight-carbon-containing volatiles (C8-VOCs). In an
      orchard of T. uncinatum, truffles producing different concentrations of C8-VOCs
      clustered around distinct host trees. This clustering was not associated with
      maturity, but was associated with fungal genotype. * These results indicate that
      the variation in C8-VOCs in truffles is most likely under genetic control. They
      exemplify that understanding the factors behind aroma variability requires a
      holistic approach. Furthermore, they also raise new questions regarding the
      ecological role of 1-octen-3-ol in truffles.

PMID- 22394029
TI  - Reliability of the Dynamic Gait Index (Finnish version) in individuals with
      neurological disorders.
AB  - PURPOSE: To produce a Finnish version of the Dynamic Gait Index (DGI) and
      establish its reliability in people with neurological disorders affecting
      balance. METHOD: A consecutive sample of 33 participants in inter-rater and 30
      participants in intra-rater sample were tested. The DGI was administered in two
      testing sessions 1-2 h apart. Reliability was assessed with the intra-class
      correlation coefficient (ICC), Bland-Altman 95% limits of agreement, coefficient
      of reproducibility (CR), and standard error of the mean (SEM). RESULTS: The
      instructions from the original DGI were preserved during the translation process
      with no need for cultural adaptations. The relative reliability of the total
      scores proved to be high in inter-rater (ICC = 0.90) and intra-rater (ICC = 0.91)
      testing. The relative reliability between single items varied from poor to high
      in inter-rater (r = 0.57-0.96) and intra-rater (r = 0.20-0.97) testing. Absolute
      reliability of the total score was high, and in single items, it varied similarly
      to relative reliability. The SEM was 1.2 points in inter-rater and 0.8 points in
      intra-rater testing. CONCLUSIONS: The Finnish version of DGI was produced and
      found to be a reliable tool for clinical testing of balance in neurological
      patients with balance disorder.

PMID- 22394030
TI  - Impact of the reactive microenvironment on the bone marrow involvement of
      follicular lymphoma.
AB  - AIMS:   Follicular lymphoma (FL) is associated with bone marrow (BM) involvement
      in approximately 40-70% of cases. Previous studies have suggested that the immune
      microenvironment of FL plays an important role in the clinical behaviour of the
      disease. To investigate the role of the microenvironment in BM involvement of FL,
      we performed immunophenotypical analysis of the reactive cell populations in
      lymph nodes (LN) and corresponding BM of 35 patients with FL. Microenvironment
      patterns of BM infiltrates were compared to the corresponding features of the LN
      in cases with BM manifestation, and the LN microenvironment was compared in FL
      cases with and without BM involvement. METHODS AND RESULTS:   Automated image
      segmentation-based quantitation was performed in whole digital slides of tissue
      microarrays of formalin-fixed paraffin-embedded tissue biopsies. We found
      significantly more CD8(+) T lymphocytes, forkhead box protein 3 (FoxP3)(+) T
      lymphocytes and CD68(+) macrophages and fewer PD1(+) T lymphocytes in the BM than
      in the matching LN samples. Furthermore, we observed significantly fewer CD8(+) T
      cells and CD68(+) macrophages in cases involving the BM compared to those
      localized only to the LNs. CONCLUSIONS:   Our study showed that different tumour
      cell growth in the LN and BM may generate different microenvironments, and
      suggested that the reduced number of cytotoxic T lymphocytes and macrophages in
      LNs favours BM infiltration of neoplastic cells in FL.

PMID- 22394031
TI  - Impaired endothelium-dependent and -independent relaxation of aorta from diabetic
      rats.
AB  - Vascular complication in diabetes has been reported to be due to the effects of
      chronic high blood glucose on the vascular system. Different relaxation
      mechanisms exist in the vasculature and effect of chronic high glucose on
      vascular relaxation mechanisms is not clearly understood. We assessed the effect
      of streptozotocin (STZ, 70 mg/kg, for 12 wks)-induced diabetes on vascular
      reactivity to isoproterenol (Isop, 10-9-10-5 M), a cAMP-dependent agent,
      acetylcholine (ACh, 10-9-10-5 M), a stimulant of NO (nitric oxide) synthase,
      sodium nitroprusside (SNP, 10-10-10-5 M), NO donor, or bradykinin (BK, 10-9-10-5
      M) in the rat isolated aortic ring. Isop, ACh, SNP, or BK dose-dependently
      relaxed phenylephrine (PE, 10-7 M) pre-constricted ring producing a maximum
      relaxation of 82 % for Isop (10-5 M), 85 % for ACh (10-5 M), 100 % for SNP (10-6
      M), and 30 % for BK (10-5 M) respectively. STZ attenuated Isop, ACh, and BK
      induced relaxation by 45 % (n=7, pn (Fig. 5, Ref. 24).

PMID- 22394033
TI  - Plasma leptin levels in rats with induced Toxoplasma gondii infection.
AB  - BACKGROUND: To explore the changes in plasma leptin levels of rats with induced
      Toxoplasma gondii infection. METHODS: The study was conducted on 20 Spraque
      Dawley type adult male rats, which were equally divided into two groups. Group 1,
      general control group. Group 2, infection group (rats in this group were infected
      with live Toxoplasma gondii parasite, which was injected in 0.5 ml serum
      physiologic through intraperitoneal route, so that 10-12 parasites were seen in
      the area under a light microscope). Blood samples collected from all animals 4
      weeks after the infection were analyzed to determine plasma leptin levels (RIA).
      RESULTS: There was no significant difference between the body weights of groups 1
      and 2 at the end of the study. Plasma leptin levels in the infection group (group
      2) were significantly higher than those in group 1 (p<0.01). CONCLUSION:
      Toxoplasma gondii infection can cause an increase in leptin secretion without
      changing body weight in a period of 4 weeks in rats (Tab. 1, Ref. 25).

PMID- 22394032
TI  - The effect of acute swimming exercise on plasma melatonin levels in rats.
AB  - BACKGROUND: This study aims to determine the changes in plasma melatonin levels
      of rats performing acute swimming exercise, immediately following the exercise
      and after 24 and 48 hours. METHODS: The study included 40 Spraque Dawley species
      adult male rats divided in to 4 groups as follows: group 1: general control
      group, group 2: swimming group A, the animals were decapitated after performing
      30-minute acute swimming exercise, group 3: Swimming group B, the animals were
      decapitated 24 hours after performing 30-minute acute swimming exercise and group
      4: swimming group C, the animals were decapitated 48 hours after performing 30
      minute acute swimming exercise. Blood samples were collected from all
      experimental animals by decapitation method and plasma melatonin levels were
      determined according to RIA method. RESULTS: The comparison of plasma melatonin
      levels among groups revealed that group 3 had the highest plasma melatonin levels
      (p<0.01). The levels in group 1 (control) and group 4 were not different. The
      lowest plasma melatonin levels were found in group 2 (p<0.01). CONCLUSION: The
      results of our study demonstrate that plasma melatonin levels that decrease
      immediately after acute swimming exercise increase significantly after 24 hours
      and restore to resting levels after 48 hours (Tab. 1, Ref. 15).

PMID- 22394034
TI  - DNA relatedness and serotyping of Leptospira strains.
AB  - BACKGROUND: In a previous study (5), the constructed phylogenetic tree for
      leptospires belonging to 12 different serovars common in Central Europe made the
      prediction of serovar from knowing the genotype and vice versa possible.
      OBJECTIVE: The study was aimed at investigation of the usefulness of such
      procedure to distinguish in between at present to us available and worldwide
      accepted reference strains of pathogenic Leptospira serovars. MATERIAL AND
      METHODS: One hundred and seventy seven Leptospira strains representing different
      serovars were tested. DNA fingerprints of these strains were performed, digitally
      captured and as described earlier of those phylogenetic tree using different
      fingerprinting software was constructed using UPGMA clustering method with band
      matching by the Dice coefficient (5). RESULTS: At this tree, 145 of 177
      Leptospira strains tested each took a unique position, and the remaining 32
      strains were distributed at 15 different positions (each of 14 positions taken by
      two different strains and one position taken by four strains). CONCLUSION: The
      constructed phylogenetic tree likely to be very useful in prediction of
      Leptospira serovar in most cases of an infection so the saving time and being
      helpful in serovar identification of the pathogenic agent (Fig. 1, Ref. 9).

PMID- 22394035
TI  - Detection of point mutations in KRAS oncogene by real-time PCR-based genotyping
      assay in GIT diseases.
AB  - OBJECTIVES: The determination of gene mutations is important for the diagnosis
      and prognosis of various gastrointestinal cancers. The aim of our study was to
      develop a new procedure for the analysis of KRAS gene mutation by application of
      the real-time PCR method. BACKGROUND: The detection process requires discriminate
      trace amount of mutant allele in a large excess of wild-type DNA in various
      samples. METHODS: The real-time PCR based technique using hybridization probes
      for five most frequently KRAS codon 12 mutations and WT specific peptide nucleic
      acid (PNA) was performed. Our multiplex detection system was tested in various
      DNA samples (tissue, bile, pancreatic juice) of patients with different diagnoses
      of gastrointestinal tract disease obtained by endoscopy and ERCP. RESULTS: We
      designed and optimized the real-time PCR conditions and tested various amount of
      PNA in PCR reaction to suppress amplification of the wild-type DNA. We determined
      the interassay variability of the melting temperatures and the results of
      mutation testing were confirmed by DNA sequencing with the 100 % accuracy.
      Incidence of searched mutations was 67.5 % in cohort of 40 patients; for KRASG12D
      it was in 44.4 %, KRASG12V in 22.2 %, KRASG12S in 14.8 %, KRASG12A in 14.8 % and
      KRASG12C in 3.8 %. The sensitivity of the assays is 1x10-5. CONCLUSIONS:
      Advantages of this technique are rapidity, accuracy and it is generally easy to
      perform. This method can be adapted for synchronic detection of multiple
      mutations and after readjustment by other type mutation of KRAS gene may serve as
      useful clinical tool for analyzing point mutations in various clinical samples
      (Tab. 3, Fig. 3, Ref. 42).

PMID- 22394036
TI  - Homocysteine Slovakia study: study design and occurrence of hyperhomocysteinaemia
      and other risk factors.
AB  - BACKGROUND: Slovakia belong to the European Union countries with the high
      incidence and prevalence of cardiovascular diseases in general and IHD in
      particular. METHOD: Homocystein-Slovakia is crossectional population study
      realised in subjects in high risk age 35-75 years in two groups. The first
      consists of patients with verified stable ischemic heart disease (IHD) (M= 152; F
      = 167) aged 60.8+/-9.37 yrs (males) res. 63.1+/-7.56 years (females) (NS) who
      were randomly selected from two cardiological registrars. Second population was
      formed by general population who were dichotomised according their medical
      records into IHD patients (M= 31, F= 53) and apparently healthy controls (M= 47;
      F = 55), the later in significantly younger age as patients, but in same age for
      intergender comparison 49.6+/-10.3 vs 46.6+/-9.2 yrs (NS). RESULTS: We found very
      high prevalence of classic as well as newer risk factors and risk markers both in
      IHD patients and in controls. Increased homocysteinen (Hcy >15 umo/l for males
      and Hcy >13 umo/l for females) was found even in 32.9 % of patients and 13.6 % of
      controls (p<0.001). Comparison of regulating vitamins levels between IHD patients
      and controls demonstrated similar prevalence. CONCLUSION: Homocystein Slovakia
      study found very high prevalence of hyperhomocysteinemia in patients with stable
      ischemic heart disease. Even the prevalence in healthy controls correspond to
      data reported for MI patients in Western countries. Vitamins regulating
      metabolism of homocysteine also shown high prevalence, however, without
      differences between IHD patients and controls (Tab. 5, Fig. 1, Ref. 27).

PMID- 22394037
TI  - Low density lipoprotein size in relation to carotid intima-media thickness in
      coronary artery disease.
AB  - OBJECTIVE: With increasing interest in the role of non-traditional lipid risk
      factors in coronary artery disease, we undertook this study to relate LDL
      subclass size and carotid intima-media thickness of the common carotid artery in
      coronary artery disease patients. METHODS: The study was conducted in 106
      patients during their first visit (study group I) and after 12 months (study
      group II). Intima-media thickness of the common carotid artery was determined
      using B-mode ultrasound. Separation of LDL subclasses was preformed by 3-31 %
      polyacrylamide gradient gel electrophoresis. RESULTS: LDL3 was the dominant
      subclass in both study groups, but there was statistically significant difference
      in the distribution of dominant LDL subclasses (p<0.01). The mean carotid intima-
      media thickness was significantly increased (p<0.001) in coronary artery disease
      patients after 12 months period. There was significant negative correlation
      between intima-media thickness and LDL size in both study groups (p<0.05). Intima
      media thickness was not significantly correlated with plasma lipid
      concentrations. Multiple regression analyses show that strongest independent
      predictor of the intima-media thickness variation was diastolic blood pressure,
      followed by LDL size and age, and accounted for 29 % of the observed variability
      in intima-media thickness. CONCLUSION: LDL particle size is independently
      associated with carotid intima-media thickness in coronary artery disease
      patients with normal levels of traditional lipid risk. These results imply that
      small, dense LDL subclasses are an important indicator for assessing
      atherosclerosis and its progression (Tab. 4, Ref. 39).

PMID- 22394038
TI  - Iron accumulation in human spleen in autoimmune thrombocytopenia and hereditary
      spherocytosis.
AB  - BACKGROUND: Although the iron is an essential element for the physiological
      functions of cells, tissues and organs, it is also an important inductor of
      reactive oxygen species (ROS). MATERIAL AND METHODS: Three groups of human spleen
      with autoimmune thrombocytopenia (AITP), hereditary spherocytosis (HS) and
      reference samples stained by haematoxylin and eosin, Perls' reaction for nonheme
      Fe(III) iron and Alcian blue for glycoconjugates detection were studied. RESULTS:
      Positive Perls' reaction in both AITP and HS groups was seen. Higher positivity
      in the HS than in AITP group was observed. HS group showed a higher amount of
      acidic glycoconjugates deposits than AITP group. Iron overload in HS and AITP
      leads to overproduction of ROS. CONCLUSION: We suggest that acidic
      glycoconjugates deposits are involved in antioxidant defence by elimination and
      restriction of iron as a ROS inducer (Fig. 4, Ref. 19).

PMID- 22394039
TI  - Tumor markers panel and tumor size of ovarian dermoid tumors in reproductive age.
AB  - OBJECTIVE: To study whether there is any relationship between a serum tumor
      markers panel (CA19-9, CA 125, CEA, CA15-3 and AFP) and the tumor size in
      patients with ovarian dermoid cyst in reproductive age. BACKGROUND: Between
      January 2006-2007, 160 patients were operated in the Department of Infertility,
      Zekai Tahir Burak Women Health Hospital due to ovarian dermoid cyst. METHODS: The
      clinical data and serum tumor markers levels of operated patients were retrieved
      from the records of the department. This was a retrospective study. RESULTS:
      Forty-four patients (37.6 %) had high levels of CA 19-9 , twenty-seven patients
      (19.3 %) had high CA 125 levels, eleven patients (9.4 %) had high levels of CEA,
      five patients (4 %) had high levels of CA 15-3 and one patient (0.9 %) had high
      AFP levels at the time of initial surgery. The bilaterality rate was 8.1 %. When
      grouping the tumor size as 10 cm, the mean serum levels of tumor markers had
      significantly increased by increasing the tumor size (p<0.05) for CA 19-9, CA
      125, CEA. CONCLUSIONS: Our study suggests that serum CA 19-9 is probably more
      accurate marker than other tumor markers in the ovarian dermoid cysts. Also, the
      most important parameter that affects CA 19-9 elevation in the dermoid cysts, is
      the tumor size. As the tumor becomes bigger, this relationship becomes more
      distinct (Tab. 2, Ref. 15).

PMID- 22394040
TI  - Effects of abdominal compartment syndrome on gastric emptying time.
AB  - INTRODUCTION: Increase in intra-abdominal pressure may affect gastric emptying
      time but the precise effect has not been demonstrated. Effects of acute increase
      of intra-abdominal pressure on gastric emptying time can not be demonstrated in
      clinical or experimental studies. In this study we aimed to study the effect of
      increased intra-abdominal pressure on gastric emptying time. METHODS: Six male
      stray dogs that weighed 20-25 kg were studied. Following the induction of general
      anaesthesia, an abdominal catheter was placed and intra-abdominal pressure was
      raised at a rate of 5 cm H2O every 10 minutes using intra-abdominal
      administration of physiologic saline solution until 45 cm H2O pressure was
      reached. Gastric emptying time was measured scintigraphically at the beginning of
      the study (IAB 0 cm H2O ) and again four hours later when pressure reached the
      maximum value (IAP was 45 cm H2O). RESULTS: Gastric emptying time for baseline
      pressure was in average 51.83+/-13.16 whereas for 45 cm H2O pressure it was in
      average 90.83+/-26.96. This difference was found statistically significant
      (p<0.05). The differences between baseline values and values after increased
      intra-abdominal pressure were statistically significant (Tab. 4, Fig. 1, Ref.
      26).

PMID- 22394041
TI  - Comparison of self-gripping mesh with mesh fixation with fibrin-glue in
      laparoscopic hernia repair (TAPP).
AB  - AIM: Comparison of self-gripping mesh with fibrin-glue mesh fixation for
      laparoscopic hernia repair using TAPP technique. MATERIALS AND METHODS: The trial
      has a prospective randomized design. The primary end-point was the evaluation of
      pain at 2 days, 1 month, and 3 months after surgery. The pain occurring 3 months
      after the surgery was considered as chronic pain. RESULTS: We have compared a
      group of 50 patients with self-gripping mesh with a group of 50 patients with
      fibrin glue mesh fixation using TAPP technique. There was no statistical
      difference between the basic group parameters (sex distribution, average age).
      There was no significant difference between the groups in terms of postoperative
      pain 1 month and 3 months after the surgery (p>0.05). There was no patient with
      chronic pain at 3-month follow-up in our trial. The mean operation time was 44
      minutes in the group with self-gripping mesh and 48.5 minutes in the group with
      fibrin glue mesh fixation. There was a significant difference between both groups
      (p=0.006) CONCLUSION: Both fixation methods appear to be a well-tolerated
      alternative to classical methods for mesh fixation with clips. According to our
      trial there is no difference in the postoperative pain incidence in self-gripping
      mesh and fibrin glue mesh fixation groups for laparoscopic hernia repair. Our
      data has showed that self-gripping mesh represents a tendency to a faster
      technique in comparison with fibrin-glue fixation. Both techniques are easy-to
      use. There is no superior technique according to our trial (Tab. 2, Fig. 2, Ref.
      23).

PMID- 22394042
TI  - Matrix metalloproteinases and their inhibitors in correlation to proliferative
      and classical tumour markers during surgical therapy of colorectal liver
      metastases.
AB  - OBJECTIVES: Classical and proliferative tumour markers and matrix
      metalloproteinases and their tissue inhibitors reflect the features of malignancy
      and are useful in prediction of prognosis in patients with colorectal liver
      metastases. There is very limited information about their physiological functions
      during regeneration and healing of liver parenchyma after any type of liver
      surgery for malignancy. METHODS: The presented study included the patients, who
      underwent following surgical procedures for CLM, benign liver lesions and
      inguinal hernias: Group A: 22 patients with inguinal hernias, Group B: 26
      patients with benign liver lesions, Group C: 30 patients with colorectal liver
      metastases (CLM) who were treated by radiofrequency ablation, Group D: 41
      patients with CLM who underwent a radical surgical therapy - resection, and Group
      E: 22 patients with inoperable CLM who underwent an explorative laparotomy
      without any surgical procedure. RESULTS: The preoperative and postoperative serum
      levels of CEA, CA 19-9, TK, TPA, TPS, MMP-2, MMP-9, TIMP-1, and TIMP-2 were
      statistically analyzed and compared within the groups to estimate the influence
      of a surgical procedure type. These results reflect the influence of surgical
      procedure on the serum levels of studied tumour markers during operation.
      CONCLUSIONS: It was the first description using these types of comparison to all
      metalloproteinases, their inhibitors, and proliferative and classical tumour
      markers. It could help us to estimate the critical relations of these tumour
      markers in prognoses of disease free survival or overall survival in patients
      after a surgical procedure for CLM (Tab. 5, Ref. 26).

PMID- 22394043
TI  - Fundus autofluorescence in age-related macular disease imaged with a laser
      scanning ophthalmoscope.
AB  - Age-related macular degeneration (ARMD) as the most common cause of legal
      blindness in industrialized countries remains an incompletely understood, complex
      retinal disease. Prophylactic and therapeutic options are still limited.
      Sensitive diagnostic tools and prognostic markers to evaluate disease stage and
      progression in the individual patient are needed. The retinal pigment epithelium
      (RPE) plays a key role in the disease process both in early and late variants of
      AMD. An excessive accumulation of lipofuscin granules in the lysosomal
      compartment of RPE cells represents a common downstream pathogenetic pathway in
      various retinal diseases including AMD. Fundus autofluorescence (FAF) imaging
      allows the visualization of the topographic distribution of lipofuscin over large
      retinal areas (Fig. 3, Ref. 13).

PMID- 22394044
TI  - Prevalence of cleft lip and palate in western Slovakia in the years 2001-2007.
AB  - OBJECTIVES: The aim of this study was to investigate the prevalence of orofacial
      clefts (OC) in live newborns from 2001 to 2007 in Western Slovakia and correlate
      their occurrence with a number of relevant seasonal and geographical factors and
      epidemiological trend of this condition. In this study we used retrospective
      active survey collecting clinical data of 220 children with OC registered and
      operated at the cleft centre in Bratislava. Our study group included 67 patients
      from Bratislava region and 151 patients from the remaining Western Slovakia
      (Nitra, Trnava, Trencin regions). Data of live births was obtained from Health
      Statistics of the Slovak Republic. RESULTS: Total incidence (TI) of 1.49/1000
      live births (LB) in the region of Western Slovakia in 2001-2007 marked a decrease
      of prevalence compared to 1.64/1000 LB in the years 1985-2000. Bratislava region
      dominated in total prevalence of 1.82/1000 LB compared to the rest of Western
      Slovakia regions with 1.37/1000 LB. Most observed cleft type was the CP with 38.6
      % frequency, followed by CLP with 35.5 % and CL with a frequency of 24.1 %. The
      frequency of AM with 1.82 % was the lowest. CONCLUSION: The results showed that
      the frequency risk rate of a birth of a child with OC was 1 to 671 LB in Western
      Slovakia. The data proved a higher prevalence of OC in Bratislava region with 1
      child with this type of congenital anomaly to 549 LB compared with 1 child with
      OC to 730 LB in the rest of the Western Slovakia regions (Tab. 7, Ref. 16).

PMID- 22394045
TI  - Variations of the celiac trunk and its branches associated with the shift of
      vascular hilum (porta hepatis) of the liver.
AB  - The knowledge of vascular variations, like other anatomical variations, is
      important during the operative, diagnostic and endovascular procedures in
      abdomen. This report describes variations in the celiac trunk and abnormal entry
      of hepatic arteries into the liver as found during routine dissection in
      approximately 65 years old female cadaver. The celiac trunk was two inches long
      and gave 2 inferior phrenic arteries, a left gastric artery, and then bifurcated
      into a splenic and a common hepatic artery. The common hepatic artery gave rise
      to left hepatic artery, which entered the liver through fissure for ligamentum
      venosum. The common hepatic artery then divided into right hepatic and
      gastroduodenal arteries. The cystic artery was a branch of the left hepatic
      artery. The porta hepatis of the liver was situated on the right side of the
      caudate lobe.The knowledge of variation reported here is important during
      endovascular procedures, cholecystectomy and liver transplantation from the
      living donors (Fig. 2, Ref. 18).

PMID- 22394046
TI  - Digital mammography - a new trend in breast carcinoma diagnostics.

PMID- 22394047
TI  - Herbs as alternate in treating acne.

PMID- 22394048
TI  - Staging of black esophagus.

PMID- 22394049
TI  - Experimental and theoretical evaluation of multisite cadmium(II) exchange in
      designed three-stranded coiled-coil peptides.
AB  - An important factor that defines the toxicity of elements such as cadmium(II),
      mercury(II), and lead(II) with biological macromolecules is metal ion exchange
      dynamics. Intriguingly, little is known about the fundamental rates and
      mechanisms of metal ion exchange into proteins, especially helical bundles.
      Herein, we investigate the exchange kinetics of Cd(II) using de novo designed
      three-stranded coiled-coil peptides that contain metal complexing cysteine
      thiolates as a model for the incorporation of this ion into trimeric, parallel
      coiled coils. Peptides were designed containing both a single Cd(II) binding
      site, GrandL12AL16C [Grand = AcG-(LKALEEK)(5)-GNH(2)], GrandL26AL30C, and
      GrandL26AE28QL30C, as well as GrandL12AL16CL26AL30C with two Cd(II) binding
      sites. The binding of Cd(II) to any of these sites is of high affinity (K(A) > 3
      * 10(7) M(-1)). Using (113)Cd NMR spectroscopy, Cd(II) binding to these designed
      peptides was monitored. While the Cd(II) binding is in extreme slow exchange
      regime without showing any chemical shift changes, incremental line broadening
      for the bound (113)Cd(II) signal is observed when excess (113)Cd(II) is titrated
      into the peptides. Most dramatically, for one site, L26AL30C, all (113)Cd(II) NMR
      signals disappear once a 1.7:1 ratio of Cd(II)/(peptide)(3) is reached. The
      observed processes are not compatible with a simple "free-bound" two-site
      exchange kinetics at any time regime. The experimental results can, however, be
      simulated in detail with a multisite binding model, which features additional
      Cd(II) binding site(s) which, once occupied, perturb the primary binding site.
      This model is expanded into differential equations for five-site NMR chemical
      exchange. The numerical integration of these equations exhibits progressive loss
      of the primary site NMR signal without a chemical shift change and with limited
      line broadening, in good agreement with the observed experimental data. The
      mathematical model is interpreted in molecular terms as representing binding of
      excess Cd(II) to surface Glu residues located at the helical interfaces. In the
      absence of Cd(II), the Glu residues stabilize the three-helical structure though
      salt bridge interactions with surface Lys residues. We hypothesize that Cd(II)
      interferes with these surface ion pairs, destabilizing the helical structure, and
      perturbing the primary Cd(II) binding site. This hypothesis is supported by the
      observation that the Cd(II)-excess line broadening is attenuated in
      GrandL26AE28QL30C, where a surface Glu(28), close to the metal binding site, was
      changed to Gln. The external binding site may function as an entry pathway for
      Cd(II) to find its internal binding site following a molecular rearrangement
      which may serve as a basis for our understanding of metal complexation,
      transport, and exchange in complex native systems containing alpha-helical
      bundles.

PMID- 22394050
TI  - Linking women who test HIV-positive in pregnancy-related services to long-term
      HIV care and treatment services: a systematic review.
AB  - OBJECTIVES: To quantify attrition between women testing HIV-positive in pregnancy
      related services and accessing long-term HIV care and treatment services in low-
      or middle-income countries and to explore the reasons underlying client drop-out
      by synthesising current literature on this topic. METHODS: A systematic search in
      Medline, EMBASE, Global Health and the International Bibliography of the Social
      Sciences of literature published 2000-2010. Only studies meeting pre-defined
      quality criteria were included. RESULTS: Of 2543 articles retrieved, 20 met the
      inclusion criteria. Sixteen (80%) drew on data from sub-Saharan Africa. The
      pathway between testing HIV-positive in pregnancy-related services and accessing
      long-term HIV-related services is complex, and attrition was usually high. There
      was a failure to initiate highly active antiretroviral therapy (HAART) among 38
      88% of known-eligible women. Providing 'family-focused care', and integrating CD4
      testing and HAART provision into prevention of mother-to-child HIV transmission
      services appear promising for increasing women's uptake of HIV-related services.
      Individual-level factors that need to be addressed include financial constraints
      and fear of stigma. CONCLUSIONS: Too few women negotiate the many steps between
      testing HIV-positive in pregnancy-related services and accessing HIV-related
      services for themselves. Recent efforts to stem patient drop-out, such as the
      MTCT-Plus Initiative, hold promise. Addressing barriers and enabling factors both
      within health facilities and at the levels of the individual woman, her family
      and society will be essential to improve the uptake of services.

PMID- 22394054
TI  - Bis(imino)pyridine iron dinitrogen compounds revisited: differences in electronic
      structure between four- and five-coordinate derivatives.
AB  - The electronic structures of the four- and five-coordinate aryl-substituted
      bis(imino)pyridine iron dinitrogen complexes, ((iPr)PDI)FeN(2) and
      ((iPr)PDI)Fe(N(2))(2) ((iPr)PDI = 2,6-(2,6-(i)Pr(2)-C(6)H(3)-N=CMe)(2)C(5)H(3)N),
      have been investigated by a combination of spectroscopic techniques (NMR,
      Mossbauer, X-ray Absorption, and X-ray Emission) and DFT calculations.
      Homologation of the imine methyl backbone to ethyl or isopropyl groups resulted
      in the preparation of the new bis(imino)pyridine iron dinitrogen complexes,
      ((iPr)RPDI)FeN(2) ((iPr)RPDI = 2,6-(2,6-(i)Pr(2)-C(6)H(3)-N=CR)(2)C(5)H(3)N; R =
      Et, (i)Pr), that are exclusively four coordinate both in the solid state and in
      solution. The spectroscopic and computational data establish that the
      ((iPr)RPDI)FeN(2) compounds are intermediate spin ferrous derivatives (S(Fe) = 1)
      antiferromagnetically coupled to bis(imino)pyridine triplet diradical dianions
      (S(PDI) = 1). While this ground state description is identical to that previously
      reported for ((iPr)PDI)Fe(DMAP) (DMAP = 4-N,N-dimethylaminopyridine) and other
      four-coordinate iron compounds with principally sigma-donating ligands, the d
      orbital energetics determine the degree of coupling of the metal-chelate magnetic
      orbitals resulting in different NMR spectroscopic behavior. For
      ((iPr)RPDI)Fe(DMAP) and related compounds, this coupling is strong and results in
      temperature independent paramagnetism where a triplet excited state mixes with
      the singlet ground state via spin orbit coupling. In the ((iPr)RPDI)FeN(2)
      family, one of the iron singly occupied molecular orbitals (SOMOs) is essentially
      d(z(2)) in character resulting in poor overlap with the magnetic orbitals of the
      chelate, leading to thermal population of the triplet state and hence temperature
      dependent NMR behavior. The electronic structures of ((iPr)RPDI)FeN(2) and
      ((iPr)PDI)Fe(DMAP) differ from ((iPr)PDI)Fe(N(2))(2), a highly covalent molecule
      with a redox noninnocent chelate that is best described as a resonance hybrid
      between iron(0) and iron(II) canonical forms as originally proposed in 2004.

PMID- 22394055
TI  - Ultrafast photodynamics of drugs in nanocavities: cyclodextrins and human serum
      albumin protein.
AB  - In this feature article, we discuss recent advances in studying ultrafast dynamic
      and structural aspects of host-guest interactions. Steady-state and time-resolved
      techniques exploring events from the femto- to nanosecond regime were used to
      examine the ultrafast photodynamics and subsequent events in selected
      nanostructures of the formed complexes. These consist of aromatic systems,
      biologically relevant molecules, and drugs trapped within cyclodextrins (CD) and
      human serum albumin (HSA) protein pockets. We examine the effects exerted by
      these chemical and biological cavitands on internal twisting motions, proton
      transfer and charge transfer, and cis-trans isomerization reactions that may
      occur in the confined molecular systems. In addition, the influence of a
      restricting environment on the interaction of guest molecules with biological
      water is considered. The dynamic details of the complexes (diffusion, early
      interactions, formation, stability, internal guest diffusion, and conformational
      changes) and the excited-state relaxation pathways, rate constants of the
      involved processes, and changes in the electronic distribution within
      encapsulated guests gave clues to elucidate their photobehavior and are relevant
      to the photostability and delivery of drugs when using nanocarriers.

PMID- 22394057
TI  - A semi-autonomous model of endochondral ossification for developmental tissue
      engineering.
AB  - Bone tissue engineering is currently undergoing a paradigm shift regarding the
      concepts used to develop cell-based therapies for skeletal repair. In place of
      the "trial and error" approach, researchers aim at developing cellular concepts
      that mirror developmental and postnatal processes. Herein, we describe a model
      for in vivo endochondral remodeling of an in vitro derived cartilaginous
      intermediate and its applicability to bone engineering. In vitro differentiation
      of the continuous cell line, ATDC5, in pellet culture was enhanced in a medium
      containing ascorbic acid, insulin-transferrin-selenium, dexamethasone, and
      transforming growth factor beta1, when compared with other tested preparations.
      This differentiation was characterized by the elevated expression of Collagen
      type II and X along with glycosaminoglycan (GAG) accumulation and the onset of
      hypertrophy. On combination with NuOssTM, a clinically used bone void filler, and
      implantation in nude mice, the differentiated pellets further matured into GAG
      rich cartilaginous intermediates after 4 weeks. This was subsequently partially
      remodeled into osteocalcin-positive bone tissue after 8 weeks without further
      external manipulation, indicating the semi-autonomous nature of this implant.
      Mineralized tissue along with active osteoclast resorption and neo-angiogenesis
      was apparent throughout the implant. The bone volume was approximately eightfold
      higher (10.70%+/-0.99%) when using a cartilaginous intermediate (based on
      differentiated cell pellets) than when observed with cell-seeded scaffolds
      (1.19%+/-0.24% and 1.48%+/-0.35%), in both a differentiated and an
      undifferentiated state. This study highlights the potential of endochondral
      strategies for bone tissue engineering and allows the identification of the key
      cellular parameters for this process.

PMID- 22394056
TI  - Enhanced extinction of cocaine seeking in brain-derived neurotrophic factor
      Val66Met knock-in mice.
AB  - The Val66Met polymorphism in the brain-derived neurotropic factor (BDNF) gene
      results in alterations in fear extinction behavior in both human populations and
      mouse models. However, it is not clear whether this polymorphism plays a similar
      role in extinction of appetitive behaviors. Therefore, we examined operant
      learning and extinction of both food and cocaine self-administration behavior in
      an inbred genetic knock-in mouse strain expressing the variant Bdnf. These mice
      provide a unique opportunity to relate alterations in aversive and appetitive
      extinction learning as well as provide insight into how human genetic variation
      can lead to differences in behavior. BDNF(Met/Met)  mice exhibited a severe
      deficit in operant learning as demonstrated by an inability to learn the food
      self-administration task. Therefore, extinction experiments were performed
      comparing wildtype (BDNF(Val/Val) ) animals to mice heterozygous for the Met
      allele (BDNF(Val/Met) ), which did not differ in food or cocaine self
      administration behavior. In contrast to the deficit in fear extinction previously
      demonstrated in these mice, we found that BDNF(Val/Met)  mice exhibited more
      rapid extinction of cocaine responding compared to wildtype mice. No differences
      were found between the genotypes in the extinction of food self-administration
      behavior or the reinstatement of cocaine seeking, indicating that the effect is
      specific to extinction of cocaine responding. These results suggest that the
      molecular mechanisms underlying aversive and appetitive extinction are distinct
      from one another and BDNF may play opposing roles in the two phenomena.

PMID- 22394059
TI  - Clinical presentation, immunohistochemistry and electron microscopy indicate
      neurofibromatosis type 2-associated gliomas to be spinal ependymomas.
AB  - Neurofibromatosis type 2 (NF2) is a hereditary tumor syndrome. The hallmark of
      NF2 is bilateral vestibular schwannoma. In addition, glioma is one of the
      diagnostic criteria of NF2. In this retrospective study the clinical presentation
      and histopathological features of 12 spinal gliomas from NF2 patients were
      assessed. Ten tumors were previously diagnosed as ependymomas and two as
      astrocytomas. However, upon re-evaluation both astrocytomas expressed epithelial
      membrane antigen in a dot-like fashion and in one case it was possible to perform
      electron microscopy revealing junctional complexes and cilia typical for
      ependymoma. The findings suggest that NF2-associated spinal gliomas are
      ependymomas. Based on the fact that NF2-associated gliomas are almost exclusively
      spinal and that no NF2 mutations have been found in sporadic cerebral gliomas, we
      suggest that "glioma" in the current diagnostic criteria for NF2 should be
      specified as "spinal ependymoma".

PMID- 22394058
TI  - Metagonimoides oregonensis (Heterophyidae: Digenea) infection in Pleurocerid
      snails and Desmognathus quadramaculatus salamander larvae in Southern Appalachian
      streams.
AB  - Metagonimoides oregonensis (Heterophyidae) is a little-known digenetic trematode
      that uses raccoons and possibly mink as definitive hosts, and stream snails and
      amphibians as intermediate hosts. Some variation in the life cycle and adult
      morphology in western and eastern populations has been previously noted. In the
      southern Appalachians, Pleurocera snails and stream salamanders, e.g.,
      Desmognathus spp., are used as intermediate hosts in the life cycle. We completed
      a series of studies in this system examining some aspects of larval trematode
      morphology and first and second intermediate host use. Molecular sequencing of
      the 28S rDNA of cercariae in our survey placed them clearly within the
      heterophyid family. However, light and scanning electron microscopy revealed both
      lateral and dorso-ventral finfolds on the cercariae in our region, whereas
      original descriptions of M. oregonensis cercariae from the west coast indicate
      only a dorso-ventral finfold, so further work on the systematics of this group
      may be warranted. A survey of first intermediate host, Pleurocera proxima, from 7
      streams in the region identified only M. oregonensis, virgulate-type cercariae,
      and cotylomicrocercous-type cercariae in the streams, with M. oregonensis having
      the highest prevalence, and the only type present that use amphibians as second
      intermediate hosts. Based on clearing and staining of 6 Desmognathus
      quadramaculatus salamander larvae, we found that individual salamanders could
      have over 600 metacercariae, which form between muscle fibers throughout the
      body. Histological observations suggest that the metacercariae do not cause
      excessive tissue damage or inflammation, and likely persist through
      metamorphosis, thereby transmitting potentially large numbers of worms to
      definitive host raccoons foraging along streams.

PMID- 22394060
TI  - Profiles and alpha-amylase inhibition activity of proanthocyanidins in unripe
      Manilkara zapota (chiku).
AB  - Proanthocyanidins in unripe  Manilkara zapota  (chiku) were isolated using
      solvent extraction followed by Sephadex LH-20 fractionation with a yield of 0.9%.
      HPLC analysis using a diol column revealed well-resolved oligomers ranging from
      dimer to hexamer. The majority of the proanthocyanidins are composed of higher
      degree oligomers appearing as one large peak in the chromatogram. Analysis of the
      proanthocyanidins using LC/MS showed that (epi)gallocatechins were the dominant
      extension unit in the proanthocyanidins. In agreement with this result, thiolysis
      treatment of the proanthocyanidins using mercaptoacetic acid produced thioether
      derivatives of (epi)gallocatechins as the major product and (epi)gallocatechin
      gallate derivatives as the minor product. The mean of the degree of
      polymerization was estimated to be 9.0. From MALDI-TOF MS, B-type gallocatechin
      oligomers up to decamer could be detected. The unripe chiku proanthocyanidins are
      thus good starting material for preparation of (epi)gallocatechin derivatives.
      The proanthocyanidins was shown to inhibit alpha-amylase with an IC(50) value of
      4.2 +/- 0.2 MUg/mL and inhibit alpha-glucosidase with an IC(50) of 16.6 +/- 0.3
      MUg/mL.

PMID- 22394061
TI  - Characterization of laccase activity produced by Cryptococcus albidus.
AB  - This study deals with the characterization of laccase enzyme activity produced by
      Cryptococcus albidus. Industrial wastes like effluent and sludge are complex
      mixtures of a number of chemicals. These chemicals can interfere with the proper
      functioning of the enzymes used for bioremediation. Thus, it is important to
      study the effect of such interfering solvents, detergents, metal chelators, and
      other chemicals on enzyme activity before industrial applications. Laccase showed
      maximum activity at pH 2.5 and temperature 20-30 degrees C when ABTS was used as
      a substrate. The enzyme followed Michaelis-Menten kinetics: K(m) was 0.8158 mM
      and V(max) was 1527.74 U/mg. Laccase showed good thermostability with a half-life
      of 81 min at 25 degrees C, 77 min at 35 degrees C, 64 min at 45 degrees C, 36 min
      at 55 degrees C, and 21 min at 65 degrees C. There was no effect of sodium
      dodceyl sulfate (SDS) (0.1-1.0%) and EDTA (0.1-0.5%) on laccase activity. Sodium
      azide and 2-mercaptoethanol showed complete inhibition of laccase activity at
      0.1% concentration. At lower concentrations of acetone and acetonitrile, laccase
      was able to maintain its activity. However, the activity was completely inhibited
      at a concentration of 50% or above of acetone, methanol, 1,4-dioxan, and
      acetonitrile.

PMID- 22394062
TI  - Utilization of sweetwater as a cost-effective carbon source for sophorolipids
      production by Starmerella bombicola (ATCC 22214).
AB  - Biosurfactants are microbially synthesized surfactants that are environmental
      friendly due to low toxicity. Sophorolipid is one of the simplest biosurfactants
      with well-defined structure produced by Starmerella bombicola(ATCC 22214) on
      glucose and vegetable oil as the carbon source. The raw material cost accounts
      for 10-30% of the overall cost. Glycerol is readily available from a commercial
      fat-splitting process as sweetwater at a very low cost. Sophorolipids was
      synthesized using glycerol and sweetwater as a cost-effective carbon source. The
      glycerol was further replaced with sweetwater as a source of glycerol. Optimum
      glycerol concentration was 15% w/v with 10% w/v sunflower oil, giving 6.6 g/L of
      sophorolipids. The crude sophorolipid contains two major components; both of them
      were lactonic sophorolipids as analyzed by reverse-phase high-performance liquid
      chromatography (RP-HPLC), liquid chromatography-mass spectroscopy (LC-MS), and
      nuclear magnetic resonance ((1)H-NMR).

PMID- 22394063
TI  - Optimal production of L-threo-2,3-dihydroxyphenylserine (L-threo-DOPS) on a large
      scale by diastereoselectivity-enhanced variant of L-threonine aldolase expressed
      in Escherichia coli.
AB  - This study examined the efficient production and optimal separation procedures
      for pure L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) from a mixture of
      diastereomers synthesized by whole-cell aldol condensation reaction, harboring
      diastereoselectivity-enhanced L-threonine aldolase in Escherichia coli JM109. The
      addition of the reducing agent sodium sulfite was found to stimulate the
      production of L-threo-DOPS without affecting the diastereoselectivity ratio,
      especially at the 50 mM concentration. The optimal pH for diastereoselective
      synthesis was 6.5. The addition of Triton X-100 also strongly affected the
      synthesis yield, showing the highest conversion yield at a 0.75% concentration;
      however, the diastereoselectivity of the L-threonine aldolase was not affected.
      Lowering the temperature to 10 degrees C did not significantly affect the
      diastereoselectiviy without affecting the synthesis rate. At the optimized
      conditions, a mixture of L-threo-DOPS and L-erythro-DOPS was synthesized by
      diastereoselectivity-enhanced L-threonine aldolase from E. coli in a continuous
      process for 100 hr, yielding an average of 4.0 mg/mL of L-threo-DOPS and 60%
      diastereoselectivity (de), and was subjected to two steps of ion exchange
      chromatography. The optimum separation conditions for the resin and solvent were
      evaluated in which it was found that a two-step process with the ion-exchange
      resin Dowex 50 W * 8 and activated carbon by washing with 0.5 N acetic acid was
      sufficient to separate the L-threo-DOPS. By using two-step ion-exchange
      chromatography, synthesized high-purity L-threo-DOPS of up to 100% was purified
      with a yield of 71%. The remaining substrates, glycine and 3,4
      dihydroxybenzaldehyde, were recovered successfully with a yield of 71.2%. Our
      results indicate this potential procedure as an economical purification process
      for the synthesis and purification of important L-threo-DOPS at the
      pharmaceutical level.

PMID- 22394064
TI  - Improved cellulase production by Botryosphaeria rhodina from OPEFB at low level
      moisture condition through statistical optimization.
AB  - The response surface method was applied in this study to improve cellulase
      production from oil palm empty fruit bunch (OPEFB) by Botryosphaeria rhodina. An
      experimental design based on a two-level factorial was employed to screen the
      significant environmental factors for cellulase production. The locally isolated
      fungus Botryosphaeria rhodina was cultivated on OPEFB under solid-state
      fermentation (SSF). From the analysis of variance (ANOVA), the initial moisture
      content, amount of substrate, and initial pH of nutrient supplied in the SSF
      system significantly influenced cellulase production. Then the optimization of
      the variables was done using the response surface method according to central
      composite design (CCD). Botryosphaeria rhodina exhibited its best performance
      with a high predicted value of FPase enzyme production (17.95 U/g) when the
      initial moisture content was at 24.32%, initial pH of nutrient was 5.96, and 3.98
      g of substrate was present. The statistical optimization from actual experiment
      resulted in a significant increment of FPase production from 3.26 to 17.91 U/g
      (5.49-fold). High cellulase production at low moisture content is a very rare
      condition for fungi cultured in solid-state fermentation.

PMID- 22394065
TI  - Simple, sensitive, and quick protocol to detect less than 1 ng of bacterial
      lipopolysaccharide.
AB  - Detection and quantitation of lipopolysaccharide (LPS) are important for quality
      assurance of pharmaceutical, biopharmaceutical products and for several research
      and industrial aspects. The widely available assays for LPS detection are the
      normal, or chromogenic, and the synthetic LAL (Limulus amebocyte lysate).
      Unfortunately, both assays are expensive and could not distinguish between
      different types of bacterial LPS, while LPS silver nitrate staining requires more
      than 20 hr and can only detect 5 ng LPS. The current modified protocol was able
      to detect less than 0.5 ng LPS in a polyacrylamide-urea gel. The procedure is
      rapid, inexpensive, and reproducible. It depends on introducing two modifications
      to improve the staining sensitivity in sample buffer and staining procedure. The
      results revealed that excluding the reducing agent sucrose to use instead
      glycerol, and replacing SDS with DOC, as well as incorporation of 4 M urea in
      stacking and separating gels, increased the sensitivity up to 150 pg. In summary,
      the gels were fixed, carbohydrates moieties were oxidized to create active
      aldehydes, and the gels were silver stained using non-ammoniacal silver nitrate.

PMID- 22394066
TI  - Process development for robust removal of aggregates using cation exchange
      chromatography in monoclonal antibody purification with implementation of quality
      by design.
AB  - Aggregate removal is one of the most important aspects in monoclonal antibody
      (mAb) purification. Cation-exchange chromatography (CEX), a widely used polishing
      step in mAb purification, is able to clear both process-related impurities and
      product-related impurities. In this study, with the implementation of quality by
      design (QbD), a process development approach for robust removal of aggregates
      using CEX is described. First, resin screening studies were performed and a
      suitable CEX resin was chosen because of its relatively better selectivity and
      higher dynamic binding capacity. Second, a pH-conductivity hybrid gradient
      elution method for the CEX was established, and the risk assessment for the
      process was carried out. Third, a process characterization study was used to
      evaluate the impact of the potentially important process parameters on the
      process performance with respect to aggregate removal. Accordingly, a process
      design space was established. Aggregate level in load is the critical parameter.
      Its operating range is set at 0-3% and the acceptable range is set at 0-5%.
      Equilibration buffer is the key parameter. Its operating range is set at 40 +/- 5
      mM acetate, pH 5.0 +/- 0.1, and acceptable range is set at 40 +/- 10 mM acetate,
      pH 5.0 +/- 0.2. Elution buffer, load mass, and gradient elution volume are non
      key parameters; their operating ranges and acceptable ranges are equally set at
      250 +/- 10 mM acetate, pH 6.0 +/- 0.2, 45 +/- 10 g/L resin, and 10 +/- 20% CV
      respectively. Finally, the process was scaled up 80 times and the impurities
      removal profiles were revealed. Three scaled-up runs showed that the size
      exclusion chromatography (SEC) purity of the CEX pool was 99.8% or above and the
      step yield was above 92%, thereby proving that the process is both consistent and
      robust.

PMID- 22394067
TI  - A method for 3D detection of symmetry line in asymmetric postures.
AB  - The methods for symmetry line detection presented in the literature are typically
      suited to analyse symmetric upright postures, both standing and seated. The
      proposed method focuses on the symmetry line detection in subjects assuming
      asymmetric postures in which this line falls far outside the sagittal plane. The
      proposed approach evaluates the symmetry line by means of an autoregressive
      process in order to determine the set of planes suited to slice the back
      coherently with its geometric spatial configuration. The method is analysed
      assuming the cutaneous marking as reference and it is compared with a previous
      one, also developed by these authors. Results are analysed and critically
      discussed. 

PMID- 22394069
TI  - Phase transition from liquid to disordered solid phase of cyclooctanone studied
      with dielectric methods.
AB  - The dielectric studies performed for cyclooctanone in its static dielectric
      regime have shown that at the phase transition from liquid to disordered
      (plastic) solid phase of the compound, the following singular phenomena occur:
      (a) the static permittivity (epsilon(s)) exhibits a small increase at the
      transition, instead of that usually observed for polar liquids, a strong decrease
      of the permittivity at the transition to the crystalline solid phase; (b)
      temperature dependence of the permittivity, epsilon(s)(T), is practically the
      same in both phases, reflecting the same dipolar orientational entropy increment
      induced by the probing electric field; (c) a distinct jump occurs in the slope of
      the frequency dependence (in log-log scale) of the dielectric losses due to an
      ionic current, from the "ohmic" value -1 in the liquid phase to about -0.9 just
      after the transition to the plastic phase; (d) a similar jump is observed in the
      shape of the electric modulus spectra of cyclooctanone. The results clearly show
      the liquid-like freedom in the molecular dynamics in the plastic phase as well as
      similar intermolecular interactions in both phases of cyclooctanone. The
      differences in the dielectric losses frequency behavior may reflect the change in
      the ions dynamics: from the normal translational Brownian diffusion in the liquid
      phase to the subdiffusional dynamics in the plastic phase.

PMID- 22394068
TI  - High performance liquid chromatography analysis of anthocyanins in bilberries
      (Vaccinium myrtillus L.), blueberries (Vaccinium corymbosum L.), and
      corresponding juices.
AB  - In the present study the anthocyanin content of commercially available bilberry
      juices and fresh fruits were quantified by using 15 authentic anthocyanin
      standards via high performance liquid chromatography with an ultra-violet
      detector (HPLC-UV/VIS). Delphinidin-3-O-glucopyranoside, delphinidin-3-O
      galactopyranoside, and cyanidin-3-O-arabinopyranoside were the major anthocyanins
      found in juices, nectar, and fresh bilberries. In contrast, fresh blueberries had
      higher concentrations of malvidin-3-O-arabinopyranoside and petunidin-3-O
      galactopyranoside. Up to 438 mg anthocyanins per 100 g fresh weight (2762 mg/100
      g dry weight (DW)) were detected in blueberries from various sources, whereas
      bilberries contained a maximum of 1017 mg anthocyanins per 100 g fresh weight
      (7465 mg/100 g DW). Commercially available bilberry and blueberry juices (n= 9)
      as well as nectars (n= 4) were also analyzed. Anthocyanin concentrations of
      juices (1610 mg/L to 5963 mg/L) and nectar from bilberries (656 mg/L to 1529
      mg/L) were higher than those of blueberry juices (417 mg/L) and nectar (258 mg/L
      to 386 mg/L). We conclude that using several authentic anthocyanin references to
      quantify anthocyanin contents indicated them to be up to 53% and 64% higher in
      fresh bilberries and blueberries, respectively, than previously reported using
      cyanidin-3-O-glucoside. This study has also demonstrated that commercially
      available juices produced from bilberries contain much higher anthocyanin
      concentrations than those from blueberries. PRACTICAL APPLICATION: We have
      investigated the contents of a special class of antioxidants, namely anthocyanins
      in blueberry and billberry fruits and juices commercially available in Germany.
      To achieve reliable data we have used authentic standards for the first time. We
      think that our results are important in the field of nutritional intake of this
      important class of polyphenols and fruit juice companies get a closer insight in
      the occurrence of these antioxidants in market samples to be used in food
      composition databases and for nutritional survey.

PMID- 22394070
TI  - Basal cell carcinoma with an epidermal collarette and ductal differentiation on
      the dorsal foot.

PMID- 22394071
TI  - Environmental sensitivity of Ru(II) complexes: the role of the accessory ligands.
AB  - A suite of Ru(II) complexes in which one ligand is pH responsive and the other
      two are varied in an effort to achieve improved photophysics has been synthesized
      and their potential as pH reporters assessed. The more general purpose of the
      study was to examine the role of the accessory ligands in heteroleptic reporter
      complexes and the degree to which such ligands can affect the performance of
      luminescent reporters. For this suite of complexes, judicious choice of the
      accessory ligand can alter both the pK(a)* and the dynamic range of response. It
      was found that the emission color and brightness were influenced by pH, but the
      lifetimes were only weakly affected. Surprisingly, some accessory ligands which
      should have improved luminescent properties essentially turned off the pH
      response. Several possible reasons for this observation are explored. It is
      suggested, and density functional theory (DFT) calculations support, that the
      relative pi* levels of the pH sensitive and the accessory ligands are critical.

PMID- 22394072
TI  - Modulation of optical properties of dissolved humic substances by their molecular
      complexity.
AB  - In this study, we show that several UV-Vis absorbance, steady-state and time
      resolved fluorescence parameters of a series of dissolved humic substances (DHS)
      from different sources (e.g. terrestrial fulvic and humic acids, and humic acid
      like molecules extracted from composted and vermicomposted wastes) correlate with
      the molar absorptivity at 280 nm per mole of organic carbon (epsilon(280)), which
      in turn is proportional to the molecular complexity (e.g. molecular size,
      aromaticity and oxidation degree) of the DHS. Both absorbance and fluorescence
      spectral responses were sensitive to the molecular complexity associated with the
      maturation degree of the DHS. Depending on the DHS, different emitting responses
      by excitation at the UVA (340 nm) and VIS (460 nm) regions of the absorption
      spectra were observed. The results were explained in terms of the extent of
      intramolecular electronic interactions between electron donor groups, such as
      polyhydroxylated aromatics and indoles, and more oxidized acceptor groups (e.g.
      quinones or other oxidized aromatics) as the molecular complexity of the DHS
      increased.

PMID- 22394073
TI  - Structured exercise program improves functional capacity and delays relapse in
      euthyroid patients with Graves' disease.
AB  - PURPOSE: To evaluate short- and long-term effects of structured exercise program
      in euthyroid patients with Graves' disease. METHODS: The study employed a
      retrospective case-control design. The exercise group (n = 62) underwent 3 weeks
      of structured exercise program consisting of daily walking, strengthening, and
      stretching exercises while the control group (n = 62) participated in leisure
      activities. Thyroid profile, aerobic capacity, and perceived fatigue were
      evaluated on in-patient admission and discharge. Time to discontinuation of anti
      thyroid medication after discharge and time to relapse of symptoms were
      determined. RESULTS: The exercise group increased estimated peak oxygen
      consumption (significant group-by-time ANOVA interaction, P < 0.001), decreased
      serum thyroxin (P = 0.038), increased serum thyrotropin (P = 0.071), and reported
      less fatigue (Fisher's exact test, p < 0.001) from admission to discharge. The
      anti-thyroid medication was withdrawn within 6 months of discharge in
      significantly greater proportion of subjects in the exercise than control group
      (84% vs. 18%). Conversely, the rate of relapse within 12 months of medication
      withdrawal was smaller in the exercise (29%) than control group (72%).
      CONCLUSIONS: The results suggest that structured exercise program may normalize
      thyroid profile, improve aerobic capacity, and reduce fatigue on the short-term
      basis as well as reduce the need for anti-thyroid medication on the long-term
      basis.

PMID- 22394074
TI  - Tricellulin expression in normal and neoplastic human pancreas.
AB  - AIMS:   Tricellulin is a member of the family of tight junction proteins, which
      are found concentrated mainly at tricellular contacts. Altered expression of
      several tight junction components has been observed during carcinogenesis. In the
      present study, we have analysed the expression of tricellulin in normal human
      pancreas, and in primary exocrine and endocrine pancreatic tumours. METHODS AND
      RESULTS:   A total of 96 cases were studied: 20 normal pancreas, 58 pancreatic
      ductal adenocarcinomas, 15 pancreatic endocrine neoplasms, and three acinar cell
      carcinomas. Immunohistochemistry (analysed by digital morphometry),
      immunofluorescence, western blot analysis and reverse transcription polymerase
      chain reaction were performed. Tricellulin was localized apically in normal ducts
      and acini as intensive, spotty immunopositivity at tricellular contacts, whereas
      weaker signals were observed at the junction between two cells. Islets of
      Langerhans were negative. Well-differentiated ductal adenocarcinomas
      significantly overexpressed tricellulin as compared with poorly differentiated
      adenocarcinomas. Acinar cell carcinomas expressed tricellulin in tumour cells.
      All endocrine tumours were tricellulin-negative. CONCLUSIONS:   This is the first
      report to describe the tricellulin expression profile in normal and neoplastic
      human pancreas. Both normal and neoplastic pancreatic exocrine tissues expressed
      tricellulin, whereas no expression was seen in normal or neoplastic endocrine
      cells. Tricellulin expression in pancreatic ductal adenocarcinomas showed a
      significant negative correlation with the degree of differentiation.

PMID- 22394076
TI  - Polyhedral borane analogues of the benzynes and beyond: bonding in variously
      charged B12H10 isomers.
AB  - The effect of removing two protons, hydrogen atoms, or hydrides from the stable
      icosahedral B(12)H(12)(2-) is investigated theoretically. The resulting
      B(12)H(10)(q) (q = 4-, 2-, 0) isomers show interesting and understandable bond
      distance and stability variations, as well as special deformations associated
      with the apex-ring configuration typical of the underlying polyhedron. The
      dianions are analogous to o-, m-, and p-benzyne and have the special feature of
      distinct singlet and triplet states not far removed from each other in energy.

PMID- 22394075
TI  - Experience with endoscopy and endoscopy-assisted management of pediatric surgical
      problems: results and lessons.
AB  - Minimally invasive surgical techniques are becoming increasingly popular within
      the pediatric population. Flexible endoscopy may enhance or replace existing
      techniques in the future. Many of the reported benefits of laparoscopy and
      thoracoscopy may apply to endoscopy and endoscopy-assisted procedures; however,
      no reports exist as to the application, results, and outcomes for these
      procedures in children. It was hypothesized that endoscopy is a useful and safe
      adjunct for pediatric surgical patients. Retrospective review of medical records
      for patients who underwent endoscopy or endoscopy-assisted operations at two
      children's hospitals over 3 years (August 31, 2007-August 31, 2010) was
      completed. During this time period, 30 procedures were performed on 28 patients.
      Indications for procedure, age, operative technique, operative times, surgical
      outcomes, complications, and length of stay for each patient were reviewed.
      Patient age ranged from 3 days to 20 years. Indications for operation included
      esophageal pathology (13), gastroduodenal pathology (14), pancreatic pseudocyst
      (2), and displaced sigmoid Chait(r) (Cook, Inc., Bloomington, IN, USA) tube.
      Although endoscopy was intended only as an adjunct in all cases, the planned
      procedure was satisfactorily completed with a purely endoscopic approach in six
      cases. There were no intraoperative complications, and minor postoperative
      complications including one stricture requiring dilation, postoperative stridor,
      and esophageal leak, were each successfully managed conservatively. Endoscopy
      offers a promising adjunct to more traditional minimally invasive techniques in
      children. In some cases, endoscopy may offer an alternative to more invasive
      procedures or eliminate the need for tube thoracostomy or post-procedural
      contrast studies in some esophageal cases.

PMID- 22394077
TI  - Bruton's tyrosine kinase inhibitors: approaches to potent and selective
      inhibition, preclinical and clinical evaluation for inflammatory diseases and B
      cell malignancies.

PMID- 22394078
TI  - Lentiviral-mediated gene delivery reveals distinct roles of nucleus accumbens
      dopamine D2 and D3 receptors in novelty- and light-induced locomotor activity.
AB  - The importance of the dopaminergic system for proper brain activity is
      demonstrated by findings that alterations in this system lead to severe
      disabilities, including motor impairment observed in various neurological and
      psychiatric disorders. Although the roles of specific dopamine receptors in
      behaviour have been extensively investigated using pharmacological agents and
      knockout mice, non-specificity of ligands and compensatory molecular adaptations
      in mutated animals restrict the interpretation of the results. To overcome these
      limitations and further explore the role of the dopamine D2 and D3 receptors (D2R
      and D3R) in rats, we used lentivirus-mediated gene knockdown and overexpression
      to specifically manipulate expression levels of these genes in the rat nucleus
      accumbens (NAcc), a brain area important for spontaneous and induced locomotor
      responses. Lentiviruses, inducing expression of rat D2R or D3R, or efficient
      knockdown of either receptor by small hairpin (sh)RNAs, were stereotaxically
      injected into the NAcc. While knockdown of either receptor significantly reduced
      spontaneous locomotor activity in a novel but not in a habituated environment,
      D2R and D3R appeared to contribute in opposite ways to light-induced locomotor
      activity. D2R knockdown increased while D3R knockdown decreased locomotor
      activity in this test. Altogether, our findings suggest that D2R and D3R,
      expressed in the NAcc, have both shared and non-overlapping roles in transduction
      of alerting signals elicited by potentially important sensory and environmental
      cues.

PMID- 22394079
TI  - Target-activated coumarin phototriggers specifically switch on fluorescence and
      photocleavage upon bonding to thiol-bearing protein.
AB  - A new concept in which only the molecular target, such as a thiol-bearing
      protein, can activate the phototrigger has been demonstrated. Such target
      activatable phototriggers comprise three parts: a 7-aminocoumarin phototrigger,
      an electron acceptor (maleimide) that efficiently quenches the coumarin excited
      state, and a caged leaving group attached to the coumarin. In the absence of
      mercaptans, photoinduced electron transfer between coumarin and maleimide
      effectively blocks both the fluorescence and photocleavage pathways. Thiol
      bearing molecules, however, readily annihilate the electron acceptor and thus
      restore the phototrigger for photorelease of the caged cargo (e.g., biotin).
      Unlike traditional phototriggers, functional-group-activated phototriggers allow
      easy handling under ambient light, report specific bonding to the target, and
      enable photocleavage capability selectively at the binding site in situ, thus
      effectively positioning the photoreleased cargo at the target. Meanwhile, the
      unique feature of thiol-specific activation of the fluorescence and photocleavage
      make our new phototrigger a universal tool that can be used to identify
      accurately protein cysteine S-nitrosylation, a physiologically important
      posttranslational modification.

PMID- 22394080
TI  - Hybrid silica-PVA nanofibers via sol-gel electrospinning.
AB  - We report on the synthesis of poly(vinyl alcohol) (PVA)-silica hybrid nanofibers
      via sol-gel electrospinning. Silica is synthesized through acid catalysis of a
      silica precursor (tetraethyl orthosilicate (TEOS) in ethanol-water), and fibers
      are obtained by electrospinning a mixture of the silica precursor solution and
      aqueous PVA. A systematic investigation on how the amount of TEOS, the silica-PVA
      ratio, the aging time of the silica precursor mixture, and the solution rheology
      influence the fiber morphology is undertaken and reveals a composition window in
      which defect-free hybrid nanofibers with diameters as small as 150 nm are
      obtained. When soaked overnight in water, the hybrid fibers remain intact,
      essentially maintaining their morphology, even though PVA is soluble in water. We
      believe that mixing of the silica precursor and PVA in solution initiates the
      participation of the silica precursor in cross-linking of PVA so that its -OH
      group becomes unavailable for hydrogen bonding with water. FTIR analysis of the
      hybrids confirms the disappearance of the -OH peak typically shown by PVA, while
      formation of a bond between PVA and silica is indicated by the Si-O-C peak in the
      spectra of all the hybrids. The ability to form cross-linked nanofibers of PVA
      using thermally stable and relatively inert silica could broaden the scope of use
      of these materials in various technologies.

PMID- 22394081
TI  - Comparison of walking parameters obtained from the young, elderly and adults with
      support.
AB  - Data mining techniques are highly useful in the study of various medical signals
      and images in order to obtain useful information to better predict the diagnosis
      or prognosis or treatment options for the patient. Study of the human walking
      pattern helps us understand the variability of motion during activities such as
      high performance walking and normal walking. A comparison of the parameters
      quantifying this variability in motion in normal young and elderly subjects and
      the subjects who need support will aid in better understanding of the
      relationship among walking patterns, age and disabilities. In this study, we
      measured the tri-axial acceleration along three directions: anteroposterior,
      lateral and vertical. We also measured gyrational pitch, roll and yaw. These
      parameters were obtained using sensors attached to the back, left thigh and right
      thigh of the three classes of subjects (normal, elderly and adults with support)
      during the three types of exercises: 10-m normal walk, 10-m high performance walk
      and stepping. These recorded signals were then subjected to wavelet packet
      decomposition, and three entropies, namely approximate entropy and two bispectral
      entropies, were obtained from the resultant wavelet coefficients. On analysing
      these entropies, we could observe the following: (1) the entropy steadily
      decreases with the increase in age and with the presence of impairments, and (2)
      the entropy decreases among all the three types of exercises, namely normal
      walking and high performance walking. We feel that the results of this work can
      help in the design of supporting devices for elderly subjects. 

PMID- 22394082
TI  - Optimal dose finding for novel antimalarial combination therapy.
AB  - A recent discussion meeting convened by the Medicines for Malaria Venture
      examined how best to manage the discovery and preclinical pipeline to achieve
      novel combination therapies which would address the key clinical needs in
      malaria. It became clear that dose optimisation of components within combination
      therapy was a key issue in achieving antimalarial efficacy and for preserving
      that efficacy against parasite resistance emergence. This paper outlines some of
      the specific issues in malaria that cause dose-ranging and dose-optimisation
      studies to be particularly challenging and discusses the potential of factorial
      study design to address such challenges.

PMID- 22394083
TI  - High prevalence and molecular analysis of macrolide-nonsusceptible Moraxella
      catarrhalis isolated from nasopharynx of healthy children in China.
AB  - Three hundred eighty-three isolates of Moraxella catarrhalis were collected from
      healthy children aged less than 2 years in China and assessed for antimicrobial
      resistance. We found that 92.2% (n=353) produced a beta-lactamase.
      Nonsusceptibility rates to erythromycin and azithromycin, determined using
      Clinical Laboratory Standards Institute (CLSI) breakpoints, were 40.3% and 22.5%,
      respectively; nonsusceptibility rates determined using
      pharmacokinetics/pharmacodynamics breakpoints, however, were 59% and 60.1%. The
      minimal inhibitory concentration (MIC)(90) values were >256 MUg/ml.
      Nonsusceptibility rates varied by region from 9.7% in Dongguan to 75.9% in Jinan.
      Further, concomitant resistance to beta-lactam antibiotics was also observed.
      Pulsed-field gel electrophoresis analysis of 27/37 high-level macrolide-resistant
      M. catarrhalis isolates showed that closely related pulsotypes dominated, with a
      total of 11 different pulsotypes being observed. The closely related pulsotypes
      were observed in isolates originating from all six Chinese cities investigated,
      possibly as a consequence of the mobility of the Chinese population. Sixteen
      patterns of 23S rRNA mutations were found among 97 selected isolates using
      polymerase chain reaction and sequencing, but no known ermA, ermB, mefA, or mefE
      genes could be detected. Mutations A2982T and A2796T in 23S rRNA were related to
      high-level macrolide resistance (MICs ranging from 24 to >256 MUg/ml), while an
      A2983T mutation was associated with low-level macrolide resistance (MICs ranging
      from 0.19 to 16 MUg/ml).

PMID- 22394084
TI  - Prevalence and characterization of multidrug-resistant and extended-spectrum beta
      lactamase-producing Escherichia coli from pediatric wards of a Malaysian
      hospital.
AB  - The emergence of Escherichia coli resistant to extended-spectrum cephalosporins
      (ESCs) is of concern as ESC is often used to treat infections by Gram-negative
      bacteria. One-hundred and ten E. coli strains isolated in 2009-2010 from children
      warded in a Malaysian tertiary hospital were analyzed for their antibiograms,
      carriage of extended-spectrum beta-lactamase (ESBL) and AmpC genes, possible
      inclusion of the beta-lactamase genes on an integron platform, and their genetic
      relatedness. All E. coli strains were sensitive to carbapenems. About 46% of
      strains were multidrug resistant (MDR; i.e., resistant to >=3 antibiotic classes)
      and almost half (45%) were nonsusceptible to ESCs. Among the MDR strains, high
      resistance rates were observed for ampicillin (98%), tetracycline (75%), and
      trimethoprim/sulfamethoxazole (73%). Out of 110 strains, bla(TEM-1) (49.1%),
      bla(CTX-M) (11.8%), and bla(CMY-2) (6.4%) were detected. Twenty-one strains were
      ESBL producers. CTX-M-15 was the predominant CTX-M variant found and this is the
      first report of a CTX-M-27-producing E. coli strain from Malaysia. Majority
      (3.1%) of the strains harbored class 1 integron-encoded integrases with a
      predominance of aadA and dfr genes within the integron variable region. No gene
      cassette encoding ESBL genes was found and integrons were not significantly
      associated with ESBL or non-ESBL producers. Possible clonal expansion was
      observed for few CTX-M-15-positive strains but the O25-ST131 E. coli clone known
      to harbor CTX-M-15 was not detected while CMY-2-positive strains were genetically
      diverse.

PMID- 22394085
TI  - Editorial comment to genome-wide transcriptome analysis of fluoroquinolone
      resistance in clinical isolates of Escherichia coli.

PMID- 22394086
TI  - A decade of Australian Rural Clinical School graduates--where are they and why?
AB  - INTRODUCTION: The Australian Rural Clinical School (RCS) initiative has been
      addressing the rural medical workforce shortage at the medical education level
      for over a decade. A major expectation of this initiative is that it will improve
      rural medical workforce recruitment and subsequent retention through a rurally
      based undergraduate clinical training experience. The longitudinal nature of
      these workforce initiatives means that definitive evidence of its impact on the
      shortage of rural doctors is yet to be provided; however, to date cross-sectional
      studies are accumulating a measure of efficacy for these initiatives by
      monitoring early career factors such as internship location choice and speciality
      choice of RCS graduates. This article reports on a study in one RCS that is
      monitoring the impact of rural undergraduate clinical training on trends in
      workforce participation patterns of its graduates as long as 9 years in the
      workforce. Career location and speciality choice are reported as well as
      perspectives on early career intentions and the reality of making career and life
      decisions as a doctor in the medical workforce. METHODS: A longitudinal mixed
      methods sequential explanatory design employed a quantitative data collection
      phase followed by a qualitative phase with the merging of data sources during the
      interpretation and analysis. In 2007 a database was established that maintained
      the contact details of all former graduates since 2002. Every 2 years graduates
      are invited to participate in a survey and provide an update on the influences on
      their current career intentions/decisions. The qualitative sample was recruited
      through a survey question asking for interest in participating in an interview.
      RESULTS: The whole-sample survey results showed that out of a 64% (N = 115)
      response rate, 40% of respondents were currently working in non-urban locations.
      The majority (<n = 51, 53%) had been out in the workforce for 5 to 7 years and
      general practice was the most frequent speciality choice. Out of 29 interviewees,
      just over half (n = 16, 55%) were currently working in non-urban locations and
      primarily in general practice. The majority (n = 17, 58%) had been out in the
      workforce for 5 to 6 years. Overall they perceived that the primary drivers
      influencing their early career/life decisions were personal/family reasons and
      speciality training requirements. CONCLUSIONS: The study highlighted what is
      obvious but often overlooked in recruitment strategies for medical students and
      prevocational doctors: the significance of the inevitable life decisions that
      frequently take precedence over career intentions. A decade on there is strong
      endorsement for the positive influence that rural undergraduate clinical training
      has on promoting rural career intentions. However the fulfilment of these
      intentions is at risk when competing with concurrent personal/life choices and
      while based in an urban training environment. Provision of a continuum of
      postgraduate training opportunities in rural and regional settings that include a
      rural focus for specialties such as surgery, anaesthetics and obstetrics could:
      (1) satisfy speciality training requirements; (2) focus life decisions in a rural
      environment; and (3) keep rural career intentions viable and congruent with other
      life goals. The overriding message is: the longer the exposure to training in the
      rural context, the greater the impact on interest in future rural practice and,
      particularly, the greater the likelihood that important life decisions will also
      be made in the rural context.

PMID- 22394087
TI  - Morphological differentiation of eggs of Ancylostoma caninum, Ancylostoma
      tubaeforme, and Ancylostoma braziliense from dogs and cats in the United States.
AB  - The establishment of cat- and dog-derived laboratory strains of Ancylostoma
      braziliense allowed for a morphological comparison of the eggs of A. braziliense,
      Ancylostoma caninum, and Ancylostoma tubaeforme. The length, width, and perimeter
      were determined for images of 10 eggs each of A. braziliense from the feces of a
      dog infected with a canine isolate and a cat infected with a feline isolate, A.
      caninum from dog feces, and A. tubaeforme from cat feces. The specific identity
      of the eggs was verified by polymerase chain reaction and restriction fragment
      length polymorphism by using HinfI and RsaI restriction digests followed by gel
      electrophoresis and sequencing. The mean (+/-SD) length, width, and perimeter and
      the length-to-width ratio (+/-SD) (all measurements are in micrometers) for the
      eggs of each species were as follows: A. braziliense eggs (combined cat and dog
      source), 53.03 +/- 2.33, 36.37 +/- 1.35, 140.43 +/- 2.56, and 1.46 +/- 0.11; A.
      caninum eggs, 63.92 +/- 5.28, 39.21 +/- 1.52, 161.99 +/- 9.30, and 1.63 +/- 0.13;
      and A. tubaeforme eggs, 61.44 +/- 3.05, 39.14 +/- 1.40, 157.98 +/- 5.81, and 1.57
      +/- 0.08. The eggs of A. braziliense were significantly (P < 0.001) smaller than
      the eggs of A. caninum and A. tubaeforme in all dimensions. Thus, the eggs seem
      to be readily distinguishable using light microscopy, thereby aiding in species
      identification in fecal samples for a more comprehensive clinical picture and
      assessment of zoonotic risk.

PMID- 22394088
TI  - Cynarin-rich sunflower (Helianthus annuus) sprouts possess both antiglycative and
      antioxidant activities.
AB  - The present study examined the antiglycative and antioxidant properties of four
      edible sprouts popular in Chinese markets. In a protein-reducing sugar model, the
      sunflower sprout Helianthus annuus exhibited the strongest inhibitory effects
      against the formation of advanced glycation end products (AGEs). At a
      concentration of 1.0 mg/mL, its inhibitory rate achieved 83.29%, which is
      stronger than that of aminoguanidine (1 mM), a well-known synthetic antiglycative
      agent (with an inhibitory rate of 80.88%). The antioxidant capacity of H. annuus
      was also much stronger than other sprout samples in terms of free radical
      scavenging and reducing properties. An active ingredient contributing to the
      observed activities was identified as cynarin (1,5-dicaffeoylquinic acid). This
      is the first report of the novel function of cynarin to intervene against
      glycoxidation. Given the key roles of AGEs and oxidation in the pathogenesis of
      diabetes, the sunflower sprout H. annuus rich in cynarin may be regarded as a
      beneficial food choice for diabetic patients.

PMID- 22394089
TI  - Efficient fluorescence turn-on probe for zirconium via a target-triggered DNA
      molecular beacon strategy.
AB  - It is well-known that Zr(4+) could selectively bind with two phosphate
      functionalized molecules through a coordinate covalent interaction to form a
      sandwich-structured complex (-PO(3)(2-)-Zr(4+)-PO(3)(2-)-). In this paper, we for
      the first time converted such interaction into fluorescence sensing systems for
      Zr(4+) via a target-triggered DNA molecular beacon strategy. In the new designed
      sensing system, two phosphorylated and pyrene-labeled oligonucleotides were
      chosen as both recognition and reporter units, which will be linked by target
      Zr(4+) to form a hairpin structure and bring the two labeled pyrene molecules
      into close proximity, resulting in a "turn-on" excimer fluorescence signal.
      Moreover, gamma-cyclodextrin was introduced to afford an amplified fluorescence
      signal and, therefore, provided an improved sensitivity for the target Zr(4+).
      This allows detection of Zr(4+) with high sensitivity (limit of detection, LOD =
      200 nM) and excellent selectivity. The proposed sensing system has also been used
      for detection of Zr(4+) in river water samples with satisfactory result.

PMID- 22394090
TI  - Sensitive detection of small molecules by competitive immunomagnetic-proximity
      ligation assay.
AB  - A novel detection method of small molecules, competitive immunomagnetic-proximity
      ligation assay (CIPLA), was developed and described in this report. Through the
      proximity effect caused by special proximity probes we prepared, small molecules
      can be detected using only one monoclonal antibody. CIPLA overcomes the obstacle
      that the proximity ligation assay (PLA) cannot be used in small molecular
      detection, as two antibodies are unable to combine to one small molecule due to
      its small molecular structure. Two small molecular compounds, clenbuterol (CLE)
      and ractopamine (RAC), were selected as targets for CIPLA. The limit of detection
      (LOD) reached 0.01 ng mL(-1), which was 10-50-fold lower than ELISA. With 5
      orders of magnitude of the dynamic range achieved, the excellent sensitivity and
      broad dynamic range of CIPLA are noted. It can be applied widely in the sensitive
      detection of many other small molecular materials such as pesticides, additives
      in food, drugs, and biological samples, which have great significance in both
      theoretical and practical aspects.

PMID- 22394091
TI  - Nicotine, cotinine, and myosmine determination using polymer films of tailor
      designed zinc porphyrins as recognition units for piezoelectric microgravimetry
      chemosensors.
AB  - Two electropolymerizable zinc porphyrins with receptor sites tailor-designed for
      selective recognition of the nicotine, cotinine, or myosmine alkaloids were
      synthesized. These were 5-(2-phenoxyacetamide)-10,15,20
      tris(triphenylamino)porphyrinato zinc(II) 1 and 5-(2,5-phenylene
      bis(oxy)diacetamide)-10,15,20-tris(triphenylamino)porphyrinato zinc(II) 2
      featuring one and two pendant amide side "pincers", respectively, and three
      triphenylamine substituents at the meso positions of the porphyrin macrocycles
      capable of electrochemical polymerization. Thin polymerfilms of these porphyrins
      served for recognition and the piezoelectric microgravimetry (PM) for analytical
      signal transduction of a new chemical sensor devised for determination of these
      alkaloids. The films were deposited by potentiodynamic electropolymerization on
      the 10 MHz quartz resonators of the electrochemical quartz crystal microbalance
      (EQCM) without affecting the electronic structure of the porphyrin macrocycles.
      Under favorable flow injection analysis (FIA) conditions, the alkaloid analytes
      were determined at the concentration level of 0.1 mM with high sensitivity and
      selectivity. Affinity toward the analytes of the polymer of 2 was higher than
      that of 1 due to the higher binding ability offered by two pendant pincers of the
      former. Because of the selective receptors and PM applied under FIA conditions,
      the developed procedure offered an alternative to the time-consuming and
      relatively expensive high-performance liquid chromatography (HPLC), capillary
      electrophoresis (CE), and gas chromatography mass spectrometry (GC-MS) methods of
      detection and quantification of these alkaloids.

PMID- 22394092
TI  - Analysis of nonhuman N-glycans as the minor constituents in recombinant
      monoclonal antibody pharmaceuticals.
AB  - Minor N-linked glycans containing N-glycolylneuraminic acid residues and/or alpha
      Gal epitopes (i.e., galactose-alpha1,3-galactose residues) have been reported to
      be present in recombinant monoclonal antibody (mAb) therapeutics. These
      contaminations are due to their production processes using nonhuman mammalian
      cell lines in culture media containing animal-derived materials. In case of the
      treatment of tumors, we inevitably use such mAbs by careful risk-benefit
      considerations to prolong patients' lives. However, expanding their clinical
      applications such as for rheumatism, asthma, and analgesia demands more careful
      evaluation of the product characteristics. The present work for detailed
      evaluations of N-glycans demonstrates the methods using capillary electrophoresis
      with laser-induced fluorescence detection (CE-LIF) and a combination of high
      performance liquid chromatography and electrospray ionization time-of-flight mass
      spectrometry. The CE-LIF method provides excellent separation of both major and
      minor N-glycans from six commercial mAb pharmaceuticals within 30 min and clearly
      indicates that a possible trigger of immunogenicity in humans due to the presence
      of nonhuman N-glycans is present. We strongly believe that the proposed method
      will be a powerful tool for the analysis of N-glycans of recombinant mAb products
      in various development stages, such as clone selection, process control, and
      routine release testing to ensure safety and efficacy of the products.

PMID- 22394093
TI  - Paper-based electrochemical sensing platform with integral battery and
      electrochromic read-out.
AB  - We report a battery-powered, microelectrochemical sensing platform that reports
      its output using an electrochromic display. The platform is fabricated based on
      paper fluidics and uses a Prussian blue spot electrodeposited on an indium-doped
      tin oxide thin film as the electrochromic indicator. The integrated metal/air
      battery powers both the electrochemical sensor and the electrochromic read-out,
      which are in electrical contact via a paper reservoir. The sample activates the
      battery and the presence of analyte in the sample initiates the color change of
      the Prussian blue spot. The entire system is assembled on the lab bench, without
      the need for cleanroom facilities. The applicability of the device to point-of
      care sensing is demonstrated by qualitative detection of 0.1 mM glucose and
      H(2)O(2) in artificial urine samples.

PMID- 22394094
TI  - Surface tension measurement at the microscale by passive resonance of capillary
      waves.
AB  - The properties of fluid interfaces increase in importance as the physical scale
      decreases and, hence, characterization of surface tension becomes all the more
      critical. However, there is to date no method to characterize this parameter on
      microscale surfaces. We propose here a simple method based on the resonance of
      capillary waves, which are naturally excited by thermal fluctuations, under one
      dimensional spatial restrictions using single-beam dynamic light scattering. The
      principle was verified at methanol/air interfaces in polydimethylsiloxane (PDMS)
      microchannels having various widths. Characteristic comb-shape power spectra were
      experimentally obtained. Theoretical analysis showed that the spectral peaks
      correspond to the first or higher modes of the capillary wave resonance in the
      restricted space between the parallel channel walls. A useful relation between
      successive modes was derived to eliminate the effects of damping at the soft PDMS
      walls. Thus, for methanol, two values were calculated from three successive modes
      (24.8 and 21.2 mN/m); the literature value is 22.02 mN/m. For acetonitrile, the
      value obtained was 28.2 +/- 5 mN/m, close to the literature value of 28.6 mN/m.
      Although accuracy and precision require further elucidation, this novel method is
      expected to become a powerful tool at the micro/nanoscale.

PMID- 22394096
TI  - Antioxidant efficacy of extracts produced from pickled and dried mustard in
      rapeseed and peanut oils.
AB  - Antioxidant efficacy of 70% ethanol extract (EE), 70% methanol extract (ME), and
      water extract (WE) produced from pickled and dried mustard (Brassica juncea Coss.
      var. foliosa Bailey) was evaluated in rapeseed and peanut oils by using the
      Schaal oven method. The protective effects of aforesaid 3 extracts in stabilizing
      vegetable oils were tested by measuring their peroxide values, conjugated diene
      values, and p-anisidine values during storage of 15 d at 60  degrees C. Results
      showed that the different solvent extracts produced from pickled and dried
      mustard, at concentrations of 0.5% and 1.0% (w/w) in vegetable oils, could
      significantly (P < 0.05) lower the peroxide value, conjugated diene value, and p
      anisidine value of oils during storage at 60  degrees C. However, the extracts at
      various concentrations showed a less antioxidant effect than butylated
      hydroxytoluene (BHT) at 200 ppm. The ultraviolet spectra of different extracts
      exhibited a single maximum absorbance at 268 nm. The qualitative analysis of
      antioxidants present in the extracts was carried out by reverse phase high
      performance liquid chromatography (HPLC) using a C18 column. Two phenolic
      compounds, gallic and protocatechuric acids, were identified. The antioxidant
      activity of the extracts might be attributed to the presence of these phenolics.
      These results indicated that the pickled and dried mustard could be used as a
      potential source of natural antioxidants. PRACTICAL APPLICATION: The antioxidant
      activity of extracts produced from pickled and dried mustard toward rapeseed and
      peanut oils oxidation and the characterization of active phenolic compounds may
      be useful in developing natural antioxidants for vegetable oils. Moreover, the
      extracts could safely be used as potential antioxidant to suppress lipid
      oxidation in lipid-containing food products.

PMID- 22394097
TI  - Uniform carbon layer coated Mn3O4 nanorod anodes with improved reversible
      capacity and cyclic stability for lithium ion batteries.
AB  - A facile one-step solvothermal reaction route to large-scale synthesis of carbon
      homogeneously wrapped manganese oxide (Mn(3)O(4)@C) nanocomposites for anode
      materials of lithium ion batteries was developed using manganese acetate
      monohydrate and polyvinylpyrrolidone as precursors and reactants. The synthesized
      Mn(3)O(4)@C nanocomposites were characterized by X-ray diffraction, field
      emission scanning electron microscopy, high resolution transmission electron
      microscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy. The
      synthesized tetragonal structured Mn(3)O(4) (space group I41/amd) samples display
      nanorodlike morphology, with a width of about 200-300 nm and a thickness of about
      15-20 nm. It is shown that the carbon layers with a thickness of 5 nm are
      homogeneously coated on the Mn(3)O(4) nanorods. It is indicated from lithium
      storage capacity estimation that the Mn(3)O(4)@C samples display enhanced
      capacity retention on charge/discharge cycling. Even after 50 cycles, the
      products remains stable capacity of 473 mA h g(-1), which is as much 3.05 times
      as that of pure Mn(3)O(4) samples. Because of the low-cost, nonpollution, and
      stable capacity, the carbon homogeneously coated Mn(3)O(4)@C nanocomposites are
      promising anode material for lithium ion batteries.

PMID- 22394098
TI  - David Gilichinsky.

PMID- 22394099
TI  - Absorption band III kinetics probe the picosecond heme iron motion triggered by
      nitric oxide binding to hemoglobin and myoglobin.
AB  - To study the ultrafast movement of the heme iron induced by nitric oxide (NO)
      binding to hemoglobin (Hb) and myoglobin (Mb), we probed the picosecond spectral
      evolution of absorption band III (~760 nm) and vibrational modes (iron-histidine
      stretching, nu(4) and nu(7) in-plane modes) in time-resolved resonance Raman
      spectra. The time constants of band III intensity kinetics induced by NO
      rebinding (25 ps for hemoglobin and 40 ps for myoglobin) are larger than in Soret
      bands and Q-bands. Band III intensity kinetics is retarded with respect to NO
      rebinding to Hb and to Mb. Similarly, the nu((Fe-His)) stretching intensity
      kinetics are retarded with respect to the nu(4) and nu(7) heme modes and to Soret
      absorption. In contrast, band III spectral shift kinetics do not coincide with
      band III intensity kinetics but follows Soret kinetics. We concluded that,
      namely, the band III intensity depends on the heme iron out-of-plane position, as
      theoretically predicted ( Stavrov  ,   S. S. Biopolymers     2004  ,   74  ,   37
      - 40  ).

PMID- 22394100
TI  - Synthesis, structure, and aromaticity of the nickel(II) complex of pyricorrole, a
      molecular hybrid of porphyrin and corrole.
AB  - Formal migration of one meso-carbon atom in the porphyrin ring into the pyrrole
      moiety results in an isomer "pyricorrole", a pyridine-containing corrole
      macrocycle. We prepared the nickel(II) complex of pyricorrole by the nickel(II)
      induced cyclization of a linear precursor. Electronic absorption and proton NMR
      spectra of this compound revealed the presence of an 18pi-electron circuit over
      the macrocycle, suggesting that aromaticity was retained after  intensive
      rearrangement of the porphyrin core. X-ray crystallography of the nickel(II)
      complex confirmed the planar structure and demonstrated that it possesses  hybrid
      properties of porphyrin and corrole.

PMID- 22394101
TI  - Leaves of Japanese oak (Quercus mongolica var. crispula) mitigate photoinhibition
      by adjusting electron transport capacities and thermal energy dissipation along
      the intra-canopy light gradient.
AB  - We investigated the morphological and physiological acclimation of leaves grown
      within a canopy of Japanese oak tree (Quercus mongolica var. crispula) in terms
      of the susceptibility to photoinhibition under various growth light conditions.
      The maximum rates of photosynthesis (P(max)) and electron transport (ETR(max))
      were higher in mature leaves grown under stronger light with higher area-based
      leaf nitrogen (N) content closely associated with higher leaf mass per area. The
      net photosynthetic (P(n)) and electron transport (ETR) rates corresponding to the
      daily peak photosynthetic photon flux density (PPFD(max)) during leaf maturation
      were almost comparable to P(max) and ETR(max), respectively. Conversely, P(n) and
      ETR at the daily average PPFD (PPFD(avg)) were substantially low in shade-grown
      leaves when compared with P(max) and ETR(max). The susceptibility to
      photoinhibition at PPFD(max), i.e. at sunflecks for the shade-grown leaves, was
      assessed by the rate of excess energy production. Although sun leaves showed
      higher rates of electron transport and thermal energy dissipation than shade
      leaves under PPFD(max) conditions, the rate of excess energy production was
      almost constant across shade to sun leaves. The shade leaves of the Japanese oak
      grown within a crown were suggested to adjust their N investment to maintain
      higher photosynthetic capacities compared with those required to maximize the net
      carbon gain, which may facilitate the dissipation of the excessive light energy
      of sunflecks to circumvent photoinhibition in cooperation with thermal energy
      dissipation.

PMID- 22394102
TI  - A new flavonoid glycoside and other constituents from Dracocephalum moldavica.
AB  - A systematic phytochemical investigation of the aerial parts of Dracocephalum
      moldavica led to the isolation of 1 new and 16 known compounds. Based on
      spectroscopic analyses, the new compound was elucidated as a flavonoid glycoside,
      acacetin-7-O-(4"-acetyl)-glucopyranoside (1). The 16 known compounds were
      identified as: 9 flavonoids (2-10), 2 lignans (11-12), 4 triterpeniods (13-16)
      and 1 menthane-type monoterpenoid (17). All the 17 compounds were reported for
      the first time from D. moldavica. Compound 1 exhibited mild radical scavenging
      activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH). Although compound 17,
      named as citrylidene malonic acid, was a known compound, it possessed an uncommon
      tricyclic dilactone skeleton, the structure was secured by X-ray crystallography.
      In addition, compound 17 was tested for cytotoxic activity against A549 cell
      line, only weak cytotoxicity was shown.

PMID- 22394103
TI  - Nucleation, growth, and repair of a cobalt-based oxygen evolving catalyst.
AB  - The mechanism of nucleation, steady-state growth, and repair is investigated for
      an oxygen evolving catalyst prepared by electrodeposition from Co(2+) solutions
      in weakly basic electrolytes (Co-OEC). Potential step chronoamperometry and
      atomic force microscopy reveal that nucleation of Co-OEC is progressive and
      reaches a saturation surface coverage of ca. 70% on highly oriented pyrolytic
      graphite substrates. Steady-state electrodeposition of Co-OEC exhibits a Tafel
      slope approximately equal to 2.3 * RT/F. The electrochemical rate law exhibits a
      first order dependence on Co(2+) and inverse orders on proton (third order) and
      proton acceptor, methylphosphonate (first order for 1.8 mM <= [MeP(i)] <= 18 mM
      and second order dependence for 32 mM <= [MeP(i)] <= 180 mM). These
      electrokinetic studies, combined with recent XAS studies of catalyst structure,
      suggest a mechanism for steady state growth at intermediate MeP(i) concentration
      (1.8-18 mM) involving a rapid solution equilibrium between aquo Co(II) and
      Co(III) hydroxo species accompanied with a rapid surface equilibrium involving
      electrolyte dissociation and deprotonation of surface bound water. These
      equilibria are followed by a chemical rate-limiting step for incorporation of
      Co(III) into the growing cobaltate clusters comprising Co-OEC. At higher
      concentrations of MeP(i) ([MeP(i)] >= 32 mM), MePO(3)(2-) equilibrium binding to
      Co(II) in solution is suggested by the kinetic data. Consistent with the
      disparate pH profiles for oxygen evolution electrocatalysis and catalyst
      formation, NMR-based quantification of catalyst dissolution as a function of pH
      demonstrates functional stability and repair at pH values >6 whereas catalyst
      corrosion prevails at lower pH values. These kinetic insights provide a basis for
      developing and operating functional water oxidation (photo)anodes under benign pH
      conditions.

PMID- 22394104
TI  - Discovery of novel 5,5-diarylpentadienamides as orally available transient
      receptor potential vanilloid 1 (TRPV1) antagonists.
AB  - We have developed a novel and potent chemical series of 5,5
      diphenylpentadienamides for targeting TRPV1 in vitro and in vivo. In this
      investigation, we examined a variety of replacements for the 5-position of
      dienamides with the goal of addressing issues related to pharmacokinetics. Our
      data suggest that substitution with alkoxy groups on the phenyl ring at the 5
      position increases their ability to penetrate the blood-brain barrier. This
      investigation culminated in the discovery of compound (R)-36b, which showed a
      good pharmacokinetic profile. In vivo, compound (R)-36b was found to be effective
      at reversing mechanical allodynia in rats in a dose-dependent manner, and it
      reversed thermal hyperalgesia in a model of neuropathic pain induced by sciatic
      nerve injury.

PMID- 22394105
TI  - Troubled bodies--troubled men: a narrative analysis of men's stories of chronic
      muscle pain.
AB  - PURPOSE: To examine how men present themselves as patients with chronic pain and
      how the men's subjective experience of pain interplay with dominant norms of
      masculinity. METHOD: The material consists of qualitative interviews with 10
      Norwegian men on rehabilitation from chronic neck pain. The data is subjected to
      narrative analysis combined with a gender-sensitive perspective. FINDINGS: The
      men's accounts of chronic pain were narrated as a series of events, displaying
      physical impairments and demanding work and troubled private affairs. Through
      rich descriptions of presumably objective facts, like heredity, physical injury
      and the character of the men's work, and comparatively little information about
      the men's personal experiences of pain and distress, a rational and self
      controlled masculinity is displayed. However, extrapolation of the analysis also
      brought out how human suffering, such as chronic headaches, the losing of control
      and of oneself, is narrated in the men's stories. CONCLUSION: Men's stories of
      chronic muscle pain display a subtle balance between following dominant norms of
      masculinity, such as being rational and in self-control, and a need to express
      vulnerability as human beings. We argue that health care professionals should be
      sensitive to the dynamics of subjectivities and cultural norms of gender within
      patients' illness stories.

PMID- 22394106
TI  - Differential etching of ZnO native planes under basic conditions.
AB  - The in situ dissolution of polished (0001), (101(-)0), and (0001(-)) surfaces of
      ZnO was studied using Atomic Force Microscopy under alkaline conditions. In
      aqueous NaOH solution the (0001) plane forms a stepped surface whereas the (0001(
      )) plane converts into more stable {101(-)1(-)} planes. Dissolution of the (101(
      )0) plane leaves a combination of (0001) and (101(-)1(-)) planes. Dissolution in
      solutions containing both NaOH and Na(3)citrate causes the (0001) plane steps to
      increase in number and reduce in height, and cause an overall increase in the
      rate of dissolution in the [101(-)0] directions. These observations are explained
      using a mechanism based on edgewise dissolution where the etching rate depends on
      the number of surface oxygen atoms per zinc atom. Large areas of single index
      faces (over 50 MUm(2)) of (0001) and (0001(-)), suitable for surface chemistry
      studies, were also generated by chemical dissolution.

PMID- 22394108
TI  - Nonalcoholic fatty liver disease: a nutritional approach.
AB  - Nonalcoholic fatty liver disease (NAFLD) is among the most common causes of
      chronic liver disease in many countries, and its prevalence is increasing. NAFLD
      is often considered to be a hepatic component of metabolic syndrome, and studies
      have established that insulin resistance plays a major role in the pathogenesis
      of NAFLD. Treatments for NAFLD primarily target insulin resistance.
      Interestingly, the most common environmental cause of insulin resistance is diet.
      This article examines the correlations between NAFLD and diet and provides some
      diet recommendations based on the most current data available.

PMID- 22394107
TI  - CD133 expression is associated with poor outcome in neuroblastoma via
      chemoresistance mediated by the AKT pathway.
AB  - AIMS:   Neuroblastoma is a frequent childhood cancer with a heterogeneous
      prognosis. CD133 expression is an independent prognostic marker for a low
      survival rate in several cancers. The aim of this study was to determine the
      prognostic value of CD133 expression in a large cohort of neuroblastoma cases, to
      define the chemoresistance of neuroblastoma cells expressing CD133, and to
      determine whether this chemoresistance is regulated by activation of the AKT
      pathway. METHODS AND RESULTS:   Two hundred and eighty samples of neuroblastoma
      were screened for CD133 expression. The sensitivity of purified CD133+
      neuroblastoma cells isolated from two human cell lines to doxorubicin,
      vincristine and cisplatin, as single agents or in combination with LY294002, an
      AKT inhibitor, was evaluated in vitro. CD133 expression was found in 100 of 280
      tumours. There was a significant association between CD133 expression and the
      following poor prognosis covariates: age, International Neuroblastoma Staging
      System stage, MYCN amplification, and phospho-AKT (pAKT) expression. Patients
      with CD133- tumours had significantly better 3-year event-free and overall
      survival than patients with CD133+ tumours. In a multivariate model, CD133
      expression was independently associated with decreased overall survival.
      CD133(high) neuroblastoma cells were significantly resistant to chemotherapy as
      compared with CD133(low) cells. Treatment of unsorted neuroblastoma cells with
      the three anticancer drugs significantly enriched the CD133+ subpopulation.
      CD133(high) cells expressed significantly higher levels of pAKT than CD133(low)
      cells. LY294002 treatment abolished the preferential survival of CD133(high)
      cells. CONCLUSIONS:   CD133 is associated with in-vitro resistance to
      chemotherapy involving activation of the AKT pathway.

PMID- 22394109
TI  - Memory for emotional words in sentences: the importance of emotional contrast.
AB  - Numerous researchers have demonstrated that emotional words are remembered better
      than neutral words. However, the effect has been attributed to factors other than
      emotion because it is somewhat fragile and influenced by variables such as the
      experimental designs employed. To investigate the role of emotion per se in
      memory for emotional words, negative-affect but low arousal emotional words were
      placed in sentence contexts that either activated high emotional meanings of the
      words (Shane died in his car last night.), or low emotional meanings of the words
      (Shane's old car died last night). The high-emotional contexts led to better
      memory than the low-emotional contexts, but only in mixed lists of emotional and
      neutral words. Additionally, the traditional emotional memory effect was also
      limited to mixed lists. The results are consistent with the idea that an
      emotional contrast is responsible for the emotional memory effect with low
      arousal emotional words.

PMID- 22394110
TI  - Directional synthesis and assembly of bimetallic nanosnowmen with DNA.
AB  - Synthesizing and assembling nanoscale building blocks to form anisotropic
      nanostructures with the desired composition and property are of paramount
      importance for the understanding and use of nanostructured materials. Here we
      report a salt-tuned synthetic strategy using DNA-modified Au nanoparticles (DNA
      AuNPs) to form Au-Ag head-body nanosnowman structures in >95% yield. We propose a
      mechanism for the formation of asymmetric Au-Ag nanosnowmen from DNA-AuNPs,
      salts, and Ag-precursor-loaded polymers. Importantly, we show that oriented
      assemblies of various nanostructures are readily obtained using nanosnowmen with
      asymmetrically modified DNA as building blocks.

PMID- 22394111
TI  - Red blood cell storage and cell morphology.
AB  - AIM: In this study, we performed weekly assessment of morphology-related
      parameters through monitoring of CPD-SAGM leuco-filtered erythrocyte concentrates
      from blood withdrawal until the 42nd day of storage. BACKGROUND: Liquid storage
      of red blood cells (RBCs) delivers a blood-derived therapeutic, which is safe,
      available, effective and affordable for most patients who need transfusion
      therapy in developed countries. However, a growing body of accumulating
      controversial evidences, from either biochemical or retrospective clinical
      studies, prompted safety concerns about longer stored RBCs. METHODS: Statistical
      image analysis through scanning electron microscope was coupled to osmotic
      fragility and erythrocyte sedimentation rate. RESULTS: We could observe that by
      day 21 more than 50% of RBCs displayed non-discocyte phenotypes. This observation
      was related to an increase in osmotic fragility, which was totally overlapped in
      day 0 controls and day 7 RBCs while only slightly augmented in day 14 samples.
      Cation dysregulation (pH internal/external alteration and potassium) might both
      reflect and trigger a negative feedback loop with metabolic fluxes and membrane
      cation pumps. CONCLUSION: Morphology parameters suggest that significant
      alterations to RBC morphology over storage duration occur soon after the 14th day
      of storage, as to become significant enough within the 21st day.

PMID- 22394112
TI  - Smaller genitals at school age in boys whose mothers were exposed to non
      persistent pesticides in early pregnancy.
AB  - Endocrine disrupting chemicals are believed to play a role in the development of
      the testicular dysgenesis syndrome. Many pesticides are known to have endocrine
      disrupting abilities. In a previous study, sons of women who were occupationally
      exposed to non-persistent pesticides in early pregnancy showed signs of impaired
      reproductive function (reduced genital size and altered serum hormone
      concentrations) at three months of age. To assess the possible long-term effects
      of prenatal pesticide exposure, the boys were re-examined at 6-11 years. The 94
      boys (59 exposed, 35 unexposed) underwent genital examinations including
      ultrasound of testicular volumes, puberty staging (Tanner), anthropometry, and
      blood sampling. Only a few of the boys had reached puberty (n = 3). Among
      prepubescent boys, testicular volume and penile length (age- and weight-adjusted)
      were reduced if mothers were exposed to pesticides. The effects were associated
      with the maternal exposure levels, so that high-exposed boys had smaller genitals
      than medium-exposed boys, who had smaller genitals than those who were unexposed.
      Boys of mothers in the high exposure group (n = 23) had 24.7% smaller testes (95%
      CI: -62.2; -10.1) and 9.4% shorter penile length (95% CI: -16.8; -1.1) compared
      with the unexposed. The testicular volume and penile length at school age could
      be tracked to measures from the same boys made at 3 months, e.g. those that had
      small testes at school age also had small testes at 3 months. Pituitary and
      testicular hormone serum concentrations did not differ between exposed and
      unexposed boys. Eight prenatally exposed boys had genital malformations (no
      unexposed). These boys had smaller testis, shorter penile length and lower
      inhibin B concentrations than prepubertal boys without genital malformations. The
      findings support the results obtained at three months of age and indicate that
      prenatal pesticide exposure has long-term effects on reproductive function in
      boys.

PMID- 22394113
TI  - Imaging trypsin activity through changes in the orientation of liquid crystals
      coupled to the interactions between a polyelectrolyte and a phospholipid layer.
AB  - In this study, we developed a new type of liquid crystal (LC)-based sensor for
      the real-time and label-free monitoring of enzymatic activity through changes in
      the orientation of LCs coupled to the interactions between polyelectrolyte and
      phospholipid. The LCs changed from dark to bright after an aqueous solution of
      poly-l-lysine (PLL) was transferred onto a self-assembled monolayer of the
      phospholipid, dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DOPG),
      at the aqueous/LC interface. Interactions between the positively charged PLL and
      the negatively charged DOPG drove the reorganization of the phospholipid
      membrane, which induced an orientational transition in the LCs from a homeotropic
      to planar state. Since the serine endopeptidase trypsin can enzymatically
      catalyze the hydrolysis of PLL, the dark-to-bright shift in the optical response
      was not observed after transferring a mixed solution of PLL and trypsin onto the
      DOPG-decorated LC interface, indicating that no orientational transitions in the
      LCs occurred. However, the optical response from dark to bright was observed when
      the mixture in the optical cell was replaced by an aqueous solution of PLL.
      Control experiments with trypsin or an aqueous mixture of PLL and deactivated
      trypsin further confirmed the feasibility of this approach. The detection limit
      of trypsin was determined to be ~1 MUg/mL. This approach holds great promise for
      use in the development of LC-based sensors for the detection of enzymatic
      reactions in cases where the biological polyelectrolyte substrates of enzymes
      could disrupt the organization of the membrane and induce orientational
      transitions of LCs at the aqueous/LC interface.

PMID- 22394114
TI  - Mucocutaneous telangiectasia - it's the tip of the iceberg.

PMID- 22394115
TI  - Anthracene-tethered ruthenium(II) arene complexes as tools to visualize the
      cellular localization of putative organometallic anticancer compounds.
AB  - Anthracene derivatives of ruthenium(II) arene compounds with 1,3,5-triaza-7
      phosphatricyclo[3.3.1.1]decane (pta) or a sugar phosphite ligand, viz., 3,5,6
      bicyclophosphite-1,2-O-isopropylidene-alpha-d-glucofuranoside, were prepared in
      order to evaluate their anticancer properties compared to the parent compounds
      and to use them as models for intracellular visualization by fluorescence
      microscopy. Similar IC(50) values were obtained in cell proliferation assays, and
      similar levels of uptake and accumulation were also established. The X-ray
      structure of [{Ru(eta(6)-C(6)H(5)CH(2)NHCO-anthracene)Cl(2)(pta)] is also
      reported.

PMID- 22394116
TI  - Robot-assisted transhiatal esophagectomy: a 3-year single-center experience.
AB  - Minimally invasive esophagectomy has emerged as an important procedure for
      disease management in esophageal cancer (EC) with clear margin status, less
      morbidity, and shorter hospital stays compared with open procedures. The
      experience with transhiatal approach robotic esophagectomy (RE) for dissection of
      thoracic esophagus and associated morbidity is described here. Between March 2007
      and November 2010, 40 patients with resectable esophageal indications underwent
      transhiatal RE at the institute. Clinical data for all patients were collected
      prospectively. Of 40 patients undergoing RE, one patient had an extensive benign
      stricture, one had high-grade dysplasia, and 38 had EC. Five patients were
      converted from robotic to open. Median operative time and estimated blood loss
      were 311 minutes and 97.2 mL, respectively. Median intensive care unit stay was 1
      day (range, 0-16), and median length of hospital stay was 9 days (range, 6-36).
      Postoperative complications frequently observed were anastomotic stricture (n=
      27), recurrent laryngeal nerve paresis (n= 14), anastomotic leak (n= 10),
      pneumonia (n= 8), and pleural effusion (n= 18). Incidence rates of laryngeal
      nerve paresis (35%) and leak rate (25%) were somewhat higher in comparison with
      that reported in literature. However, all vocal cord injuries were temporary, and
      all leaks healed following opening of the cervical incision and drainage. None of
      the patients died in the hospital, and 30-day mortality was 2.5% (1/40). Median
      number of lymph nodes removed was 20 (range, 3-38). In 33 patients with known
      lymph node locations, median of four (range, 0-12) nodes was obtained from the
      mediastinum, and median of 15 (range, 1-26) was obtained from the abdomen. R0
      resection was achieved in 94.7% of patients. At the end of the follow-up period,
      25 patients were alive, 13 were deceased, and 2 patients were lost to follow-up.
      For patients with EC, median disease-free survival was 20 months (range, 3-45).
      Transhiatal RE, by experience, is a feasible albeit evolving oncologic operation
      with low hospital mortality. The benefits include minimally invasive mediastinal
      dissection without thoracotomy or thoracoscopy. A reasonable operative time with
      minimal blood loss and postoperative morbidity can be achieved, in spite of the
      technically demanding nature of the procedure. Broader use of this technology in
      a setting of high-volume comprehensive surgical programs will almost certainly
      reduce the complication rates. Robotic tanshiatal esophagectomy with the
      elimination of a thoracic approach should be considered an option for the
      appropriate patient population in a comprehensive esophageal program.

PMID- 22394117
TI  - Utility of 4-chloro-7-nitrobenzofurazan for the spectrofluorimetric determination
      of butylated hydroxyanisole and propyl gallate in foodstuffs.
AB  - A spectrofluorimetric method is presented for the determination of 2 synthetic
      phenolic antioxidants (SPAs), butylated hydroxyanisole (BHA), and propyl gallate
      (PG) in foodstuffs. The proposed method is based on the derivatization of SPAs
      with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in phosphate buffer of pH 9.0 to yield
      a highly fluorescent brown product. The optimum experimental conditions have been
      studied carefully. Linear calibration curves were obtained over the concentration
      range of 0.20 to 40 MUg mL-1 for BHA, and 0.80 to 50 MUg mL-1 for PG, using NBD
      Cl reagent. The detection limits were 18 ng mL-1 for BHA, 55 ng mL-1 for PG.
      Intra-day and inter-day relative standard deviations at 3 different
      concentrations were determined. The high recovery values indicate the accuracy of
      the proposed methods, and low relative standard deviation values indicate good
      precision. The results presented in this report show that the applied
      spectrofluorimetric method is acceptable for the determination of the 2 SPAs in
      the foodstuffs. Other SPAs, tertiary butyl hydroquinone and butylated
      hydroxytoluene in foodstuffs do not interfere with the proposed method. PRACTICAL
      APPLICATIONS: In this spectrofluorimetric method, NBD-Cl as a derivation agent is
      used to detect synthetic phenolic antioxidants. The method specificity has been
      greatly improved; there was no interference from other commonly used phenolic
      substances.

PMID- 22394119
TI  - Time-resolved infrared absorption studies of the solvent-dependent photochemistry
      of ClNO.
AB  - The photochemistry of nitrosyl chloride (ClNO) dissolved in cyclohexane is
      investigated using ultrafast time-resolved infrared (TRIR) spectroscopy.
      Following 266 nm photolysis, the photochemistry is measured by following changes
      in optical density at frequencies spanning the N?O stretch fundamental
      transition. A photoinduced depletion in optical density is observed consistent
      with the depletion of ground-state ClNO. The depletion in optical density remains
      constant out to ~50 ps demonstrating that ClNO photodissociation is not followed
      by recombination of the Cl and NO photofragments. In addition, no evidence for
      the formation of the ClON photoisomer is observed. These results stand in
      contrast to previous studies in acetonitrile where ClNO photolysis is followed by
      geminate recombination of Cl and NO, and by the production of ClON. These
      differences in ClNO photochemistry are proposed to arise from the population of
      different excited-states caused by solvent dependence of the ground-state
      potential energy surface minimum along the Cl-N stretch coordinate. Solvent
      dependent vibrational relaxation and differences in strength of the solvent cage
      are also proposed to contribute to the solvent-dependent photochemistry. Finally,
      these results are placed in the context of recent models of ClNO photochemistry
      and role of this compound in tropospheric ozone production.

PMID- 22394118
TI  - Carbon sources and medium pH affects the growth of Withania somnifera (L.) Dunal
      adventitious roots and withanolide A production.
AB  - This work deals with optimisation of adventitious root suspension culture of
      Withania somnifera (L.) Dunal (Solanaceae) for the production of biomass and
      withanolide A and we investigated the effect of carbon source and the initial
      medium pH on growth and production of withanolide A in adventitious root cultures
      of Withania somnifera. A 2% sucrose concentration was found to be best for both
      biomass (113.58 g L(-1) fresh weight (FW) and 11.33 g L(-1) dry weight (DW)) and
      secondary metabolite accumulation (8.93 mg g(-1) DW) in the tested range of
      concentration (1-8%). The biomass of adventitious roots was optimal when the
      initial medium pH was 5.8 (113.26 g L(-1) FW and 11.33 g L(-1) DW) but the
      withanolide A production was highest at the medium pH level of 5.5 (9.09 mg g(-1)
      DW).

PMID- 22394121
TI  - Detection and expression of enterotoxin genes in endophytic strains of Bacillus
      cereus.
AB  - AIMS:   The aim of this study was to determine whether endophytic Bacillus cereus
      isolates from agronomic crops possessed genes for the nonhaemolytic enterotoxin
      (Nhe) and haemolysin BL (HBL) and, therefore, have the potential to cause
      diarrhoeal illness in humans. METHODS AND RESULTS:   PCR followed by sequencing
      confirmed the presence of enterotoxin genes nheA, nheB, nheC, hblA, hblC, hblD in
      endophytic B. cereus. All nhe genes were detected in 59% of endophytic B. cereus,
      while all hbl genes were detected in 44%. All six genes were detected in 41% of
      isolates. Enterotoxin genes were not detected in 15% of B. cereus isolates.
      Reverse transcriptase real-time PCR confirmed that endophytic B. cereus could
      express enterotoxin genes in pure culture. CONCLUSIONS:   This study showed that
      endophytic B. cereus isolates that possess genes for enterotoxin production are
      present in agronomic crops. Other endophytic B. cereus isolates lacked specific
      genes or lacked all nhe and hbl genes. Additionally, host, country of origin and
      tissue of origin had no impact on the enterotoxin genes detected. SIGNIFICANCE
      AND IMPACT OF THE STUDY:   Bacillus cereus with the potential of causing
      diarrhoeal illness in humans is a cosmopolitan endophytic inhabitant of plants,
      not incidental surface inhabitants or contaminants, as often suggested by
      previous research.

PMID- 22394120
TI  - The cis-4-amino-L-proline residue as a scaffold for the synthesis of cyclic and
      linear endomorphin-2 analogues.
AB  - Endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH(2)) is an endogenous tetrapeptide that
      combines potency and efficacy with high affinity and selectivity toward the MU
      opioid receptor, the most responsible for analgesic effects in the central
      nervous system. The presence of the Pro(2) represents a crucial factor for the
      ligand structural and conformational properties. Proline is in fact an efficient
      stereochemical spacer, capable of inducing favorable spatial orientation of
      aromatic rings, a key factor for ligand recognition and interaction with
      receptors. Here the Pro(2) has been replaced by 4(S)-NH(2)-2(S)-proline (cAmp), a
      proline/GABA cis-chimera residue. This bivalent amino acid maintains the capacity
      to influenc the tetrapeptide conformation and offers the opportunity to generate
      new linear models and unusually constrained cyclic analogues characterized by an
      N-terminal Tyr bearing a free alpha-amino group. The results indicate that the
      new analogues do not show affinity for both delta and kappa opioid receptors and
      bind only poorly to the MU receptors (for cyclopeptide 9: K(i)(MU) = 660 nM; GPI
      (IC(50)) = 1.4% at 1 MUM; for linear tetrapeptide acid 13: K(i)(MU) = 2000 nM;
      GPI (IC(50)) = 0% at 1 MUM; for linear tetrapeptide amide 15: K(i)(MU) = 310 nM;
      GPI (IC(50)) = 894 nM).

PMID- 22394122
TI  - Microgel adhesives for wet cellulose: measurements and modeling.
AB  - Nanostructured adhesive layers were prepared by adsorbing and/or grafting
      polyvinylamine (PVAm) onto carboxylated poly(N-isopropylacrylamide) (PNIPAM)
      microgels that were then assembled between layers of wet oxidized cellulose. The
      wet delamination force was measured as functions of PVAm content, PVAm molecular
      weight, coverage (mass adhesive/joint area), and the distribution of carboxyl
      groups in the PNIPAM microgels. The use of microgels is attractive because simple
      physical adsorption onto the cellulose surfaces before lamination gives much
      higher adhesive content and strength compared to the corresponding adsorbed
      linear PVAm. Wet adhesion increased with PVAm content in the microgels and the
      quantity of microgels in the joint whereas adhesion was independent of PVAm
      molecular weight. Physical adsorption of the PVAm onto/into the microgels gave
      the same adhesion as covalently coupled PVAm. Finally, the roles of microgel
      diameter, elasticity, and coverage were simulated by a simple peel adhesion model
      in which the microgels were treated as ideal springs.

PMID- 22394123
TI  - Plasma protein binding of positively and negatively charged polymer-coated gold
      nanoparticles elicits different biological responses.
AB  - The binding of proteins to nanoparticles is an important event that can determine
      the biological effect of nanoparticles in the body. We examined plasma protein
      binding to gold nanoparticles (5-20 nm) with different surface charge. Positively
      and negatively charged nanoparticles bound a range of proteins whereas neutral
      nanoparticle bound very little. As little as 25% neutral polymer on the surface
      of the charged nanoparticles inhibited protein binding, with only slight change
      in surface charge. Fibrinogen bound with high affinity to both of the charged
      nanoparticles. However, binding kinetics and protease digestion suggested that
      the binding orientation for each nanoparticle was different. Only the negatively
      charged nanoparticles induced cytokine release from THP-1 cells. While common
      proteins can bind to different nanoparticles, the biological outcome may not be
      the same. Consequently, knowledge about the composition of the protein corona is
      not sufficient to predict biological effects of nanoparticles.

PMID- 22394124
TI  - Mapping intracellular temperature using green fluorescent protein.
AB  - Heat is of fundamental importance in many cellular processes such as cell
      metabolism, cell division and gene expression. (1-3) Accurate and noninvasive
      monitoring of temperature changes in individual cells could thus help clarify
      intricate cellular processes and develop new applications in biology and
      medicine. Here we report the use of green fluorescent proteins (GFP) as thermal
      nanoprobes suited for intracellular temperature mapping. Temperature probing is
      achieved by monitoring the fluorescence polarization anisotropy of GFP. The
      method is tested on GFP-transfected HeLa and U-87 MG cancer cell lines where we
      monitored the heat delivery by photothermal heating of gold nanorods surrounding
      the cells. A spatial resolution of 300 nm and a temperature accuracy of about 0.4
      degrees C are achieved. Benefiting from its full compatibility with widely used
      GFP-transfected cells, this approach provides a noninvasive tool for fundamental
      and applied research in areas ranging from molecular biology to therapeutic and
      diagnostic studies.

PMID- 22394125
TI  - Lipid nanoparticles as novel delivery systems for cosmetics and dermal
      pharmaceuticals.
AB  - INTRODUCTION: Lipid nanoparticles are innovative carrier systems developed as an
      alternative to traditional vehicles such as emulsions, liposomes and polymeric
      nanoparticles. Solid lipid nanoparticles (SLN) and the newest nanostructured
      lipid carriers (NLC) show important advantages for dermal application of
      cosmetics and pharmaceuticals. AREA COVERED: This article focuses on the main
      features of lipid nanoparticles, in terms of their preparation and recent
      advancements. A detailed review of the literature is presented, introducing the
      importance of these systems in the topical delivery of drugs and active
      substances. EXPERT OPINION: Lipid nanoparticles are able to enhance drug
      penetration into the skin, allowing increased targeting to the epidermis and
      consequently increasing treatment efficiency and reducing the systemic absorption
      of drugs and cosmetic actives. The complete biodegradation of lipid nanoparticles
      and their biocompatible chemical nature have secured them the title of 'nanosafe
      carriers.' SLN and NLC represent a new technological era, which has been taken
      over by the cosmetic and pharmaceutical industry, which will open new channels
      for effective topical delivery of substances.

PMID- 22394127
TI  - Cyclists' helmet usage and characteristics in central and southern Malawi: a
      cross-sectional study.
AB  - The objective of this study was to determine the prevalence of, and factors
      associated with, bicycle helmet usage in southern and central Malawi. This study
      was across-sectional observation of public behaviour. The urban and rural
      roadways in southern and central Malawi were studied during the dry season. In
      total, 1900 bicyclists were observed along the roadways of southern and central
      Malawi over a four-day period. Observer ascertainment of cyclists' helmet status,
      approximate age, sex and bicycle operator or passenger status were measured. Of
      the 1900 cyclists observed, no cyclist was identified as wearing a helmet (exact
      95% CI: 0.0-0.2%). There was no variation by age, sex or operator/passenger
      status. Nearly, 91.5% of observed cyclists were males and 87.7% were operating
      the bicycle. The sizeable majority of male cyclists were classified as young
      adults from adolescence to 25 years old (47.2%) or adults over age 25 (44.9%);
      7.9% of male cyclists were pre-adolescent. Passengers were more likely to be
      female than operators (39.1% versus 4.2%), though, even for passengers, a higher
      proportion were males than females (p < 0.001). In Malawi, helmet usage is so
      rare as to be non-existent. This suggests an opportunity for significant
      improvement. Based on the observed cyclists' characteristics, interventions
      should be targeted to adult and young adult males.

PMID- 22394126
TI  - FRET enhanced fluorescent nanodiamonds.
AB  - Fluorescent nanodiamonds (FNDs) are one of the new and very promising
      biocompatible nanomaterials that can be used both as a fluorescence imaging agent
      and a highly versatile platform for controlled functionalization to target and
      deliver a wide spectrum of therapeutic agents. Among the remarkable fluorescence
      properties are excellent photostability, emission between 600-700nm, quantum
      yield of 1 and moderately long fluorescence lifetimes. However the low absorption
      cross section of fluorescent (N-V)(-) centers limits FNDs' brightness. In this
      work we show that an approach based on the Forster resonance energy transfer
      (FRET) may significantly enhance the fluorescence signal observed from a single
      ND. We demonstrate that organic dyes (fluorophores) attached to the FND surface
      can efficiently transfer the excitation energy to (N-V)(-) centers. Multiple dyes
      positioned in close proximity to the ND facile surface may serve as harvesting
      antennas transferring excitation energy to the fluorescent centers. We propose
      that, with the help of some of the functional groups present on the FND surface,
      we can either directly link flurophores or use scalable dendrimer chemistry to
      position many organic dyes at a calibrated distance. Also, the remaining multiple
      functional groups will be still available for particle targeting and drug
      delivery. This opens a new way for designing a new type of theranostics particles
      of ultrahigh brightness, high photostability, specific targeting, and high
      capacity for drug delivery. 

PMID- 22394128
TI  - Polarity reversal catalysis in radical reductions of halides by N-heterocyclic
      carbene boranes.
AB  - Otherwise sluggish or completely ineffective radical reductions of alkyl and aryl
      halides by N-heterocyclic carbene boranes (NHC-boranes) are catalyzed by thiols.
      Reductions and reductive cyclizations with readily available 1,3-dimethylimidazol
      2-ylidene borane and a water-soluble triazole relative are catalyzed by
      thiophenol and tert-dodecanethiol [C(9)H(19)C(CH(3))(2)SH]. Rate constants for
      reaction of the phenylthiyl (PhS*) radical with two NHC-boranes have been
      measured to be ~10(8) M(-1) s(-1) by laser flash photolysis experiments. An
      analysis of the available evidence suggests the operation of polarity reversal
      catalysis.

PMID- 22394129
TI  - The exemplary social emotion guilt: not so relationship-oriented when another
      person repairs for you.
AB  - Guilt is considered by many researchers to be the hallmark social emotion. Guilt
      theories perceive guilt to be a negative emotion with positive interpersonal
      consequences, and empirical research has shown guilt to motivate prosocial
      behaviours aimed at restoring the relationship with one's victims. The current
      research questions the relationship-oriented nature of this emotion. Five
      experiments reveal that when a person repairs the transgressor's damage caused to
      a victim, the transgressor's guilt feelings, reparative intentions, and prosocial
      behaviour decrease. These findings suggest that it is not the relationship with
      the victim that is important in the regulation of guilt feelings, but rather the
      reparative actions that have been undertaken. Implications for theory and
      behavioural research on guilt are discussed.

PMID- 22394130
TI  - Serum from patients with erectile dysfunction inhibits circulating angiogenic
      cells from healthy men: relationship with cardiovascular risk, endothelial damage
      and circulating angiogenic modulators.
AB  - Erectile dysfunction (ED) is an early manifestation of arteriosclerosis
      associated with endothelial damage/dysfunction and to a blunted ability of
      cultured mononuclear circulating cells (MNCs) to differentiate circulating
      angiogenic cells (CACs), putatively involved in endothelial damage repair. Here
      we explored effects of human serum (HS) from patients with ED and cardiovascular
      risk factors (VRFs) but no clinical atherosclerosis, on cultured MNCs of healthy
      men to differentiate CACs and to form colonies. Effect of HS on number of CACS
      and of colony forming units (CFUs) was correlated with circulating markers of
      endothelial damage and with angiogenic modulators. MNCs from healthy men were
      cultured in standard conditions or with 20% HS from 35 patients with ED and from
      10 healthy men. CACs were identified after 7 days of culture by uptake of
      acetylated low-density lipoprotein with concomitant binding of Ulex europaeus
      agglutinin I. CFUs were counted after 5 days of culture. Enzyme-linked
      immunosorbent assays assessed plasmatic soluble (s) form of E-selectin,
      Endothelin (ET)-1, tissue type plasminogen activator (tPA), vascular endothelial
      growth factor (VEGF)(165) and sVEGF receptor (R)-1. The number of CACs and of
      CFUs from healthy men was reduced after culturing MNCs with HS compared to
      standard medium. The inhibitory effect was significantly higher with HS from ED
      patients with higher or lower VRF exposure compared to healthy men. Inhibition
      was positively correlated with VRFs exposure, with ED severity, with common
      carotid artery intima media thickness measured using B-mode ultrasound, and to a
      lesser extent with plasmatic sE-Selectin, sET-1 and sVEGFR-1. Dysfunction of
      cells involved in vascular homoeostasis is induced by soluble factors still
      unknown and already present in a very initial systemic vascular disease in men
      with ED and VRFs.

PMID- 22394131
TI  - Working and waiting: homeless drinkers' responses to less affordable alcohol.

PMID- 22394132
TI  - Immunohistochemical analysis of the endoribonucleases Drosha, Dicer and Ago2 in
      smooth muscle tumours of soft tissues.
AB  - AIMS:   The aims of the present study were to determine the protein levels and
      cellular distribution of the endoribonucleases Drosha, Dicer and Ago2, major
      components of the microRNA-processing machinery, in benign and malignant soft
      tissue smooth muscle tumours, and to correlate the cellular levels of these
      enzymes with clinicopathological parameters including tumour histopathological
      grade. METHODS AND RESULTS:   Cellular levels of Drosha, Dicer and Ago2 were
      evaluated in 110 soft tissue leiomyosarcomas (LMS), 31 leiomyomas (LM) and normal
      smooth muscle (NSM) using immunohistochemistry. Drosha and Dicer were barely
      detectable in NSM, while augmented levels of these enzymes were observed in LM
      and LMS. This finding suggests that Drosha and Dicer are implicated in the
      development of smooth muscle neoplasms. Notably, cellular levels of Dicer were
      significantly greater in high-grade compared to low-grade LMS, implying its
      participation in the progression of these neoplasms. Ago2 was detected in NSM, as
      well as LM and LMS; its cellular levels were not associated with tumour grade.
      CONCLUSIONS:   Our results provide novel evidence that Drosha, Dicer and Ago2 are
      probably involved in the pathobiology of human smooth muscle neoplasms and that
      Dicer could serve as potentially significant biomarker for LMS progression.

PMID- 22394133
TI  - Managing the effect of hematocrit on DBS analysis in a regulated environment.

PMID- 22394135
TI  - Science and technology coming together to make a difference.
AB  - This annual meeting began in 1998 and was the first industry-led event to focus
      on the specific needs of industry researchers. The goal of Chemical and
      Pharmaceutical Structure Analysis is to provide an in-depth review of innovative
      technology and industry practices through open discussion of industry-related
      issues and needs. Education and specialized training are the foundation of all
      Chemical and Pharmaceutical Structure Analysis events - where technology and
      solutions meet.

PMID- 22394136
TI  - A systematic approach to investigate the impact of nonclinical blood processing
      deviations on large-molecule drug bioanalysis.
AB  - During nonclinical regulated toxicology studies, blood processing protocol
      deviations may negatively impact sample integrity and bioanalytical results.
      Standard practices for resolution of blood processing issues are not well
      established across the industry. In this article, using an illustrative example,
      we present a systematic approach to investigate and assess the impact of
      nonclinical blood processing protocol deviations that involve: assessment of the
      potential impact of deviations on toxicokinetic evaluation, performance of
      additional blood processing stability tests to ensure study sample integrity and
      establishment of study sample results reporting procedures to meet both
      scientific and regulatory quality requirements. This thorough and systematic
      approach can serve as a model for other analogous situations.

PMID- 22394137
TI  - Evaluation of 5-methyl-2'-deoxycytidine stability in hydrolyzed and nonhydrolyzed
      DNA by HPLC-UV.
AB  - BACKGROUND: Although the determination of 5-methyl-2'-deoxycytidine (5-MedC) in
      various biological samples is gaining increasing scientific interest, there are
      no data available regarding its stability. RESULTS: We have currently evaluated
      the stability of 5-MedC and 2'-deoxycytidine (dC) at -20 degrees C, both in
      hydrolyzed and nonhydrolyzed calf thymus DNA (CT DNA), as well as following
      repetitive freeze-thaw cycles. HPLC-UV was used for the accurate determination of
      the two 2'-deoxynucleosides. Statistical evaluation of the results revealed that
      5-MedC and dC were stable in hydrolyzed CT DNA for at least 7 days and in
      nonhydrolyzed CT DNA for at least 65 days, when these were stored at -20 degrees
      C. Furthermore, both 2'-deoxynucleosides were stable for at least three
      repetitive freeze-thaw cycles. CONCLUSION: By using HPLC-UV, we have evaluated
      the stability of 5-MedC and dC under storage conditions and repetitive freeze
      thaw cycles. Our results are informative about the way samples should be handled
      and stored in epigenetic studies.

PMID- 22394138
TI  - Facile fabrication of an interface for online coupling of microchip CE to surface
      plasmon resonance.
AB  - BACKGROUND: The aim was to develop a simple route to coupling microchip CE (MCE)
      to surface plasmon resonance (SPR). MCE is a microfluidic technology that
      utilizes microfabrication techniques to connect interacting fluid reservoirs. Its
      advantages include rapid analysis (typically seconds), easy integration of
      multiple analytical steps and parallel operation. SPR detects changes in
      refractive index within a short distance from the surface of a thin metal film as
      variations in light intensity reflected from the back of the film and, thus, does
      not require labeling. There is a great demand for developing hyphenated
      techniques like MCE-SPR that are fast, sensitive and inexpensive to analyze
      biological materials. MATERIALS & METHODS: The separation channel and flow cell
      exist as overlapping regions constructed during the microchip production and
      buffer solution was delivered mechanically. Such a design has successfully
      isolated the electrical field inherent in the MCE from the SPR detector.
      Consequently, the potential interference to the SPR signal (or modulation of the
      density of surface plasmons at the gold chip) is circumvented. RESULTS: The
      limits of detection for bovine serum albumin and sodium fluorescein were
      determined to be 7.5 uM and 3.1 mM, respectively. CONCLUSION: The technique
      described, herein, has been successfully applied in the separation of two
      species. The method offers the advantages of a near zero connection dead volume,
      electrical shielding from the separation voltage and minimization of the mass
      transfer effect.

PMID- 22394139
TI  - Mathematical simulations for bioanalytical assay development: the (un-)necessity
      and (im-)possibility of free drug quantification.
AB  - For every drug development program it needs to be discussed whether
      discrimination between free and total drug concentrations is required to
      accurately describe its pharmacokinetic behavior. This perspective describes the
      application of mathematical simulation approaches to guide this initial decision
      based on available knowledge about target biology, binding kinetics and expected
      drug concentrations. We provide generic calculations that can be used to estimate
      the necessity of free drug quantification for different drug molecules. In
      addition, mathematical approaches are used to simulate various assay conditions
      in bioanalytical ligand-binding assays: it is demonstrated that due to the
      noncovalent interaction between the binding partners and typical assay-related
      interferences in the equilibrium, a correct quantification of the free drug
      concentration is highly challenging and requires careful design of different
      assay procedure steps.

PMID- 22394140
TI  - Challenges of immunogenicity assays for vaccines.
AB  - Clinical development of vaccines requires a specific set of specialized assays to
      demonstrate the immunogenicity of the vaccine. Ideally, these assays should
      measure immune responses that correlate with protection against disease. Antibody
      responses usually correlates to protection for existing vaccines, but for
      vaccines currently in development it is not always clear which immune responses
      confer protection. Developing assays for new-generation vaccines usually requires
      working with cells, pathogens, antigens or assay controls that are not readily
      available, or are hazardous materials. Validation of these assays involves many
      challenges, and validation requirements are not yet fully specified in regulatory
      guidelines or White Papers. The different requirements for clinical vaccine
      assays and the related challenges in developing and validating these assays are
      described in this article. We provide our opinion on how to approach these
      challenges and how to apply the existing guidelines.

PMID- 22394141
TI  - Meeting the MIST regulations: human metabolism in Phase I using AMS and a tiered
      bioanalytical approach.
AB  - The metabolites in safety testing and ICH-M3 guidance documents emphasize the
      importance of metabolites when considering safety aspects for new drugs. Both
      guidances state that relevant metabolites should have safety coverage in humans
      (although the guidelines have different definitions of relevant metabolites). Not
      having safety coverage for important metabolites in humans may cause significant
      delay in the overall pharmaceutical development program. This article discusses
      the regulatory background regarding safety and metabolites, as well as outlines
      an integrated strategy taken by one pharmaceutical company, Lundbeck A/S.
      Lundbeck uses metabolite exposure data from first-in-man studies, obtained using
      an accelerator MS approach followed by a two-tiered bioanalytical investigation.
      This enables early availability of key data on this aspect and, overall,
      represents a powerful risk mitigation strategy.

PMID- 22394142
TI  - Harmonization of rules in GLP and pharmacokinetic analysis: regulatory view.
AB  - This article is an attempt to present issues associated with the principles of
      GLP system harmonization, particularly in relation to pharmacokinetic (PK)
      studies at a global scale. Complete harmonization of GLP principles requires
      unification at several levels: inside registration authorities, between key
      registration authorities, within the framework of procedures regulating
      preclinical and clinical phases of the drug-development process and within the
      framework of procedures regarding GLP principles used in PK analyses and analyses
      of residuals of veterinary drugs. This large number of discrepancies indicates
      that total harmonization of rules on this issue will be very difficult and will
      require close cooperation between institutions responsible for legislative
      processes and control of GLP principles during PK analysis.

PMID- 22394143
TI  - Recent advances in metabolomics in oncology.
AB  - The burden of cancer is growing worldwide and with it a more desperate need for
      better tools to detect, diagnose and monitor the disease is required. It is well
      recognized that cancer cells are characterized by distinct metabolic
      perturbations. The metabolomics approach involves the comprehensive profiling of
      the full complement of low MW compounds in a biological system. By applying
      advanced analytical and statistical tools, the 'metabolome' is mined for
      biomarkers that are associated with the state of cancer. This review presents an
      introduction to the main analytical platforms used in metabolomics analyses, such
      as NMR spectroscopy and MS, as well as the statistical tools used to mine these
      datasets. The discussion focuses on 'state-of-the-art' investigations on the four
      cancer types that have received the most study by metabolomics, namely breast,
      prostate, colorectal and liver cancer.

PMID- 22394144
TI  - Towards single-cell analysis for pharmacokinetics.
AB  - Traditional 'macroscopic' pharmacokinetics (PK) investigates the fate of drugs or
      toxicants administered externally to living organisms, described by the extent
      and rate of absorption, distribution, metabolism and excretion. However, how a
      single cell affects a specific pharmaceutical after administration still remains
      a largely untouched area, primarily due to the technical restrictions imposed by
      minute amounts of chemicals involved. With the fast development of high-temporal
      and spatial-resolution detection techniques and single-cell handling techniques,
      it becomes possible to pursue single-cell PK. This review summarizes useful
      methodological and experimental techniques to investigate PK at the level of the
      single cell, including the microfluidics-based single-cell manipulation and the
      MS and electrochemical methods for single-cell analysis.

PMID- 22394145
TI  - Determination and depletion of dehydroacetic acid residue in chicken tissues.
AB  - A high-performance liquid chromatography (HPLC) method was developed to determine
      dehydroacetic acid (DHA) residues in chicken muscle, liver and kidney. DHA was
      extracted using acetonitrile, and clean-up performed using a strong anion
      exchange (PAX) SPE column. The cleaned-up samples were separated by HPLC with a
      C18 column and determined at 290 nm. Extraction recoveries of DHA from samples
      fortified at 0.5-5 mg/kg levels ranged from 88.2% to 93.9% in muscle, 83.8% to
      86.6% in liver and 83.8% to 89.8% in kidney, with coefficients of variation
      <6.44%. The limit of detection was 0.05 mg/kg and limit of quantification was 0.2
      mg/kg. DHA was not detectable in muscle at 13-15 days after final administration
      of DHA, at 11 days in kidney and 17 days in liver. The method described herein is
      suitable for routine quantitative analyses of DHA in animal tissues and can be
      easily applied to the analysis of other matrices such as milk, serum and tissue
      samples from other animals.

PMID- 22394146
TI  - Facile fabrication of scalable, hierarchically structured polymer/carbon
      architectures for bioelectrodes.
AB  - This research introduces a method for fabrication of conductive electrode
      materials with hierarchical structure from porous polymer/carbon composite
      materials. We describe the fabrication of (3-hydroxybutyrate-co-3
      hydroxyvalerate) (PHBV) scaffolds doped with carbon materials that provide a
      conductive three-dimensional architecture that was demonstrated for application
      in microbial fuel cell (MFC) anodes. Composite electrodes from PHBV were
      fabricated to defined dimensions by solvent casting and particulate leaching of a
      size-specific porogen (in this case, sucrose). The cellular biocompatibility of
      the resulting composite material facilitated effective immobilization of a
      defined preparation of Shewanella oneidensis DSP-10 as a model microbial
      catalyst. Bacterial cells were immobilized via chemical vapor deposition (CVD) of
      silica to create an engineered biofilm that exhibits efficient
      bioelectrocatalysis of a simple-carbon fuel in a MFC. The functionalized PHBV
      electrodes demonstrate stable and reproducible anodic open circuit potentials of 
      320 +/- 20 mV (vs Ag/AgCl) with lactate as the electron donor. Maximum power
      densities achieved by the hierarchically structured electrodes (~5 mW cm(3)) were
      significantly higher than previously observed for graphite-felt electrodes. The
      methodology for fabrication of scalable electrode materials may be amenable to
      other bioelectrochemical applications, such as enzyme fuel cells and biosensors,
      and could easily be adapted to various design concepts.

PMID- 22394147
TI  - Synthesis and controlled self-assembly of covalently linked hexa-peri
      hexabenzocoronene/perylene diimide dyads as models to study fundamental energy
      and electron transfer processes.
AB  - We report the synthesis and photophysical characterization of a series of hexa
      peri-hexabenzocoronene (HBC)/perylenetetracarboxy diimide (PDI) dyads that are
      covalently linked with a rigid bridge. Both the ratio of the two components and
      the conjugation of the bridging element are systematically modified to study the
      influence on self-assembly and energy and electron transfer between electron
      donor HBC and acceptor PDI. STM and 2D-WAXS experiments reveal that both in
      solution and in bulk solid state the dyads assemble into well-ordered two
      dimensional supramolecular structures with controllable mutual orientations and
      distances between donor and acceptor at a nanoscopic scale. Depending on the
      symmetry of the dyads, either columns with nanosegregated stacks of HBC and PDI
      or interdigitating networks with alternating HBC and PDI moieties are observed.
      UV-vis, photoluminescence, transient photoluminescence, and transient absorption
      spectroscopy confirm that after photoexcitation of the donor HBC a photoinduced
      electron transfer between HBC and PDI can only compete with the dominant Forster
      resonance energy transfer, if facilitated by an intimate stacking of HBC and PDI
      with sufficient orbital overlap. However, while the alternating stacks allow
      efficient electron transfer, only the nanosegregated stacks provide charge
      transport channels in bulk state that are a prerequisite for application as
      active components in thin film electronic devices. These results have important
      implications for the further design of functional donor-acceptor dyads, being
      promising materials for organic bulk heterojunction solar cells and field-effect
      transistors.

PMID- 22394148
TI  - Optimum chopping conditions for Alaska pollock, Pacific whiting, and threadfin
      bream surimi paste and gel based on rheological and Raman spectroscopic analysis.
AB  - Rheological and Raman spectroscopic properties of surimi from three species
      [Alaska pollock (AP) (cold water), Pacific whiting (temperate water), and
      threadfin bream (warm water)] were investigated as affected by various chopping
      conditions. Comminuting Alaska pollock surimi at 0  degrees C demonstrated
      superior gel hardness and cohesiveness when chopping time was extended to 15-18
      min; however, long chopping time at higher temperatures resulted in a
      significantly decreased gel texture particularly at 20  degrees C. Warm water
      fish threadfin bream exhibited higher gel texture when chopping was done longer
      at higher temperature. Rheological properties were significantly affected by both
      chopping time and temperature. Species effect, based on their thermal stability,
      was readily apparent. Raman spectroscopy revealed a significant change in
      disulfide linkage and the reduction of secondary structure upon extended
      chopping. Dynamic oscillation rheology demonstrated the damage of light
      meromyoisn and lowering of onset of gelling temperature as the chopping time was
      extended. PRACTICAL APPLICATION: Chopping conditions to determine gel quality and
      manufacture surimi seafood are varied by all manufacturers. This paper covering
      three primary species for surimi with their suggested optimum chopping
      conditions: 15 min for Alaska pollock when chopped at 0  degrees C, 15 min for
      Pacific whiting at 15-20  degrees C, and 18 min for threadfin bream at 25-30 
      degrees C. The use of optimum chopping condition should maximize the value of
      each surimi and provide consistent quality to the end users.

PMID- 22394149
TI  - Clinical significance of carcinoembryonic antigen-, cytokeratin 19-, or survivin
      positive circulating tumor cells in the peripheral blood of esophageal squamous
      cell carcinoma patients treated with radiotherapy.
AB  - Circulating tumor cells (CTCs) have been associated with clinical outcome in
      various malignancies. The aim of this study was to examine CTC status in the
      peripheral blood of patients with esophageal squamous cell carcinoma (ESCC)
      before and after radiotherapy, and to evaluate its clinical significance. A total
      of 72 ESCC patients treated with radical radiotherapy were enrolled in this
      study. The nested reverse-transcriptase polymerase chain reaction was used to
      detect the three representative markers of CTCs, namely carcinoembryonic antigen,
      cytokeratin 19, and survivin. The results showed that CTC(+), a status with
      positive expression of at least one of these three markers, in patients with ESCC
      pre- and post-radiotherapy were 54.2% (39/72) and 38.9% (28/72), respectively (P=
      0.059). Furthermore, CTC (+) in patients pre- or post-radiotherapy was both
      correlated with lymph metastasis and adverse 2-year progression-free survival. It
      was also found that changes in CTC status after radiotherapy could reflect
      patients' response to radiotherapy. The response rates in cases with CTC status
      pre-radiotherapy(+)/post-radiotherapy(+), pre-radiotherapy(-)/post
      radiotherapy(+), pre-radiotherapy(-)/post-radiotherapy(-), pre
      radiotherapy(+)/post-radiotherapy(-) were 58.3% (21/36), 0% (0/3), 73.7% (14/19),
      and 85.7% (12/14), respectively. In a multivariate analysis of Cox proportional
      hazard model, only CTC (+) post-radiotherapy was an independent unfavorable
      prognostic factor for ESCC apart from subsequent chemotherapy and patients'
      Karnofsky performance status scores. In conclusion, positive detection of CTCs in
      patients with ESCC after radiotherapy may be a promising biomarker for radiation
      efficiency and prognosis assessment in ESCC.

PMID- 22394150
TI  - Customizing the hydrolytic degradation rate of stereocomplex PLA through
      different PDLA architectures.
AB  - Stereocomplexation of poly(L-lactide) (PLLA) with star shaped D-lactic acid (D
      LA) oligomers with different architectures and end-groups clearly altered the
      degradation rate and affected the degradation product patterns. Altogether, nine
      materials were studied: standard PLLA and eight blends of PLLA with either 30 or
      50 wt % of four different D-LA oligomers. The influence of several factors,
      including temperature, degradation time, and amount and type of D-LA oligomer, on
      the hydrolytic degradation process was investigated using a fractional factorial
      experimental design. Stereocomplexes containing star shaped D-LA oligomers with
      four alcoholic end-groups underwent a rather slow hydrolytic degradation with low
      release of degradation products. Materials with linear D-LA oligomers exhibited
      similar mass loss but released higher concentrations of shorter acidic
      degradation products. Increasing the fraction of D-LA oligomers with a linear
      structure or with four alcoholic end-groups resulted in slower mass loss due to
      higher degree of stereocomplexation. The opposite results were obtained after
      addition of D-LA oligomers with carboxylic chain-ends. These materials
      demonstrated lower degree of stereocomplexation and larger mass and molar mass
      loss, and also the release of degradation products increased. Increasing the
      number of alcoholic chain-ends from four to six decreased the degree of
      stereocomplexation, leading to faster mass loss. The degree of stereocomplexation
      and degradation rate were customized by changing the architecture and end-groups
      of the D-LA oligomers.

PMID- 22394151
TI  - Electronic structures of the [V(tbpy)3]z (z = 3+, 2+, 0, 1-) electron transfer
      series.
AB  - The electron transfer series of complexes [V((t)bpy)(3)](z) (z = 3+, 2+, 0, 1-)
      has been synthesized and spectroscopically characterized with the exception of
      the monocationic species. Magnetic susceptibility measurements (4-290 K)
      establish an S = 1 ground state for [V((t)bpy)(3)](3+), S = (3)/(2) for
      [V((t)bpy)(3)](2+), S = (1)/(2) for [V((t)bpy)(3)], and an S = 0 ground state for
      [V((t)bpy)(3)](1-). The electrochemistry of this series recorded in
      tetrahydrofuran solution exhibits four reversible one-electron transfer steps.
      Electronic absorption, X-band electron paramagnetic resonance (EPR), and V K-edge
      X-ray absorption (XAS) spectra were recorded. All complexes have been studied
      computationally with density functional theory (DFT) using the B3LYP functional.
      It is unequivocally shown that the electronic structure of complexes is best
      described as [V(III)((t)bpy(0))(3)](3+), [V(II)((t)bpy(0))(3)](2+),
      [V(II)((t)bpy(*))(2)((t)bpy(0))](0), and [V(II)((t)bpy(*))(3)](1-), where
      ((t)bpy(0)) represents the neutral form of the ligand and ((t)bpy(*))(1-) is the
      one-electron reduced mononanionic radical form. In the neutral and monoanionic
      members, containing two and three ((t)bpy(*))(1-) ligands, respectively, the
      ligand spins are strongly antiferromagnetically coupled to the spins of the
      central V(II) ion (d(3); S = (3)/(2)) affording the observed ground states given
      above.

PMID- 22394152
TI  - Potential antioxidant activity of the moss Bryum moravicum.
AB  - A limited number of mosses has ever been studied regarding antioxidant activity
      among which only a few are European species. As a part of our ongoing screening
      of new promising bryophyte resources of natural antioxidants, a relevant
      biological activity investigation was conducted on the moss Bryum moravicum Podp.
      (Bryaceae) collected in Germany. The antioxidant activity of an aqueous extract
      of the species was evaluated in vitro by analysing its ABTS [2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulphonic acid)] cation scavenging activity and total
      phenolic content. The study led to the detection of a moderate antioxidant
      activity: 1 mg of the extract was equivalent to 84.56 +/- 7.93 ug of ascorbic
      acid. The total phenolic content in 1 mg of the extract was equivalent to 356.44
      +/- 9.56 ug of ferulic acid used as a standard. These results have indicated for
      the first time potential importance of B. moravicum in searching for novel
      antioxidant agents.

PMID- 22394154
TI  - A facile copper-catalyzed one-pot domino synthesis of 5,12-dihydroindolo[2,1
      b]quinazolines.
AB  - A domino synthesis of 5,12-dihydroindolo[2,1-b]quinazoline derivatives via copper
      catalyzed Ullmann-type intermolecular C-C and intramolecular C-N couplings is
      reported. Good yields of various 5,12-dihydroindolo[2,1-b]quinazoline derivatives
      were obtained. Reaction scopes, limitations, and the reaction mechanism are
      discussed.

PMID- 22394155
TI  - Immunosuppressive decalin derivatives from red yeast rice.
AB  - Five new decalin derivatives (1-5), together with two known compounds (6 and 7),
      were isolated from the ethyl acetate extract of red yeast rice. Their structures
      were elucidated by means of NMR and mass spectroscopic analyses. Monascusic
      lactone A (1) is the first reported naturally occurring decalin derivative
      possessing a spiro lactone at the C-1 position. The immunosuppressive effects of
      all these isolates (1-7) on human T cell proliferation were investigated, and
      all, especially monascusic acids B (2), C (3), D (4), and A (6) and heptaketide
      (7), suppressed human T cell proliferation in a dose-dependent manner from 10 to
      100 MUM. This is the first report on the immunosuppressive activity of decalin
      derivatives.

PMID- 22394156
TI  - Traditional plant-based therapies for respiratory diseases found in North Jeolla
      Province, Korea.
AB  - OBJECTIVES: This study aims to record and conserve orally transmitted traditional
      plant-based therapies for respiratory diseases in North Jeolla Province, Korea.
      METHODS: Data were collected with semistructured questionnaires through the
      participatory rural appraisal method. RESULTS: This study reveals that overall,
      14 respiratory diseases have been treated with a total of 43 species of medicinal
      plants belonging to 40 genera in 26 families. This study also reports 149
      different modes of plant-based therapeutic application of medicinal material. The
      informant consensus factor for the common cold is 0.84, the highest among 14
      different respiratory ailments, followed by whooping cough, asthma, nosebleed,
      bronchitis, cough, and so on. Medicinal plants used to treat seven respiratory
      ailments had a 100% fidelity level. CONCLUSIONS: This study can help to preserve
      the traditional knowledge and local health traditions of North Jeolla Province
      amid rapid industrialization and urbanization. The findings of this study warrant
      follow-up clinical research to determine the most effective traditional remedies
      toward development of herbal medicinal products for integration into the Korean
      health care system.

PMID- 22394157
TI  - Integrating a complementary medicine service within a general surgery department:
      from contemplation to practice.
AB  - This article describes experience in developing a complementary and alternative
      medicine (CAM) service within a general surgery department in a public academic
      hospital in Israel. A framework is suggested for integrating CAM services within
      a hospital, based on the authors' experience, along three themes: the
      organizational structure of such a service, communication with the conventional
      team, and self-appraisal using a research-based documentation and assessment
      process. With the anticipated increase in CAM utilization within medical
      institutions, it is hoped this article will provide foundations for successful
      integration of other such services.

PMID- 22394158
TI  - Genome-wide association analysis of Sasang constitution in the Korean population.
AB  - OBJECTIVES: Sasang constitutional medicine is a traditional Korean medicine in
      which an individual is classified into one of four types of constitution: Taeum
      (TE), Soeum (SE) Soyang (SY), and Taeyang (TY). These constitution types are
      determined with biologic and physiologic characteristics, so it has been assumed
      that genetic factors are associated with each constitution type. Identifying the
      genetic elements underlying each constitution is necessary for the elucidation of
      the molecular mechanism of Sasang constitutional medicine. DESIGN: A total of
      341,998 genetic loci across the whole genome were genotyped for 1222 subjects of
      defined constitution type. The genetic loci associated with each constitution
      type were identified and the functional connectivity of genes within these loci
      was analyzed using statistical text mining. RESULTS: From the difference in
      allele frequencies between constitution types, significant genetic loci
      associated with each type were identified. Chromosomes 3q27.3 (rs10937331,
      p=2.71*10(-6)), 15q22.2 (rs7180547, p=1.58*10(-6)), and 14q22.3 (rs12431592,
      p=1.31*10(-6)) were most significantly associated with TE, SE, and SY
      constitution types, respectively. From the functional relationship analysis using
      all loci with a p-value<=10(-4), genes associated with each constitution type
      were identified. Fifteen (15) genes, including GPM6A, SYT4, and GRIK1, were
      significantly associated with the TE constitution type (p<0.05); 12 genes,
      including DRGX and AKAP11, were significantly associated with the SE constitution
      type (p<0.05); and 17 genes, including ZFP42, CDH22, ALDH1A2, OTX2, and EN2, were
      significantly associated with the SY constitution type (p<0.05). CONCLUSIONS:
      Genetic loci and genes associated with Sasang constitution types were
      systematically identified from a genome-wide association study using a large
      number of subjects.

PMID- 22394159
TI  - Safety data collection and user behaviour.

PMID- 22394160
TI  - Investigation of phase separation behavior and formation of plasmonic
      nanocomposites from polypeptide-gold nanorod nanoassemblies.
AB  - Genetically engineered elastin-like polypeptides (ELP) can be interfaced with
      cetyltrimethyl ammonium bromide (CTAB)-stabilized gold nanorods (GNRs) resulting
      in the formation of stable dispersions (nanoassemblies). Increasing the
      dispersion temperature beyond the ELP transition temperature results in phase
      separation and formation of solid-phase ELP-GNR matrices (nanocomposites). Here,
      we investigated different physicochemical conditions that influence nanocomposite
      formation from temperature-induced phase separation of ELP-GNR nanoassemblies.
      The presence of cetyltrimethyl ammonium bromide (CTAB), used to template the
      formation of gold nanorods, plays a significant role in the phase separation
      behavior, with high concentrations of the surfactant leading to dramatic
      enhancements in ELP transition temperature. Nanocomposites could be generated at
      37  degrees C in the presence of low CTAB concentrations (<1.5 mM); higher
      concentrations of CTAB necessitated higher temperatures (60  degrees C) due to
      elevated transition temperatures. The concentration of gold nanorods, however,
      had minimal influence on the phase separation behavior and nanocomposite
      formation. Further analysis of the kinetics of nanocomposite formation using a
      mathematical model indicated that CTAB largely influenced the early event of
      coacervation of ELP-GNR nanoassemblies leading to nanocomposites, but had minimal
      effect on nanocomposite maturation, which is a later-stage longer event. Finally,
      nanocomposites prepared in the presence of low CTAB concentrations demonstrated a
      superior photothermal response following laser irradiation compared to those
      generated using higher CTAB concentrations. Our results on understanding the
      formation of plasmonic/photothermal ELP-GNR nanocomposites have significant
      implications for tissue engineering, regenerative medicine, and drug delivery. 

PMID- 22394161
TI  - Selumetinib (AZD6244; ARRY-142886)  in the treatment of metastatic melanoma.
AB  - INTRODUCTION: Melanoma is the fifth most common cancer in men and seventh most
      common in women in the USA, and prognosis for patients with advanced melanoma is
      poor. The mitogen-activated protein (MAP) kinase signaling pathway is essential
      for proliferation and survival of melanoma cells. Effective inhibition of MAP
      kinase kinase (MEK) protein has been shown to downregulate the MAP kinase
      pathway, resulting in melanoma cell growth arrest and apoptosis. Selumetinib is
      an orally available, selective non-ATP-competitive MEK1 and MEK2 inhibitor. AREAS
      COVERED: In this review, the authors discuss the rationale for MEK inhibition
      therapy in melanoma and summarize data from the preclinical and clinical studies
      of selumetinib for advanced melanoma. EXPERT OPINION: As a majority of advanced
      melanomas have an activated MAP kinase signal transduction pathway, there is a
      strong preclinical rationale for investigating selumetinib in patients with
      metastatic melanoma. The results of early clinical studies of selumetinib suggest
      that selumetinib may have a role in melanoma therapy, especially in certain
      subsets of patients, such as those whose tumor harbors a BRAF mutation. Current
      studies of selumetinib are addressing the efficacy of selumetinib in these
      patients.

PMID- 22394162
TI  - Parallel-like bulk heterojunction polymer solar cells.
AB  - Here we demonstrate a conceptually new approach, the parallel-like bulk
      heterojunction (PBHJ), which maintains the simple device configuration and low
      cost processing of single-junction BHJ cells while inheriting the major benefit
      of incorporating multiple polymers in tandem cells. In this PBHJ, free charge
      carriers travel through their corresponding donor-polymer-linked channels and
      fullerene-enriched domain to the electrodes, equivalent to a parallel-like
      connection. The short-circuit current (J(sc)) of the PBHJ solar cell is nearly
      identical to the sum of those of the individual "subcells", while the open
      circuit voltage (V(oc)) is between those of the "subcells". Preliminary
      optimization of the PBHJ devices gives improvements of up to 40% in J(sc) and 30%
      in overall efficiency (eta) in comparison with single-junction BHJ devices.

PMID- 22394163
TI  - Use of 3D properties to characterize beyond rule-of-5 property space for passive
      permeation.
AB  - The application of conformationally dependent measures of size and polarity to
      characterize beyond rule-of-5 (Ro5) space for passive permeation was
      investigated. Specifically, radius of gyration, an alternative to molecular
      weight, and three-dimensional polar surface area and the generalized Born/surface
      area dehydration free energy, alternatives to hydrogen-bond donor and acceptor
      counts, were computed on models of the permeating conformations of over 35 000
      molecules. The resulting guidelines for size and polarity, described by the 3D
      properties, should aid the design of Ro5 violators with passive permeability.

PMID- 22394164
TI  - Antimicrobial efficacy of the alkaloid harmaline alone and in combination with
      chlorhexidine digluconate against clinical isolates of Staphylococcus aureus
      grown in planktonic and biofilm cultures.
AB  - AIMS:   To investigate the antimicrobial efficacy of an alkaloid, harmaline alone
      and in combination with chlorhexidine digluconate (CHG) against clinical isolates
      of Staphylococcus aureus (S. aureus) grown in planktonic and biofilm cultures.
      METHODS:   Minimum inhibitory concentrations (MICs) and minimum bactericidal
      concentrations (MBCs) were determined for each micro-organism grown in suspension
      and in biofilm using microbroth dilution method. Chequerboard assays were used to
      determine synergistic, indifferent or antagonistic interactions between harmaline
      and CHG, and the some of results were verified by confocal laser scanning
      microscopy. RESULTS:   Harmaline and CHG showed effective antimicrobial activity
      against suspensions and biofilm cultures of S. aureus, respectively. As
      determined by fractional inhibitory concentration index (FICI), synergistic
      antimicrobial effects between harmaline and CHG were observed in nine and 11 of
      the 13 S. aureus strains when in suspension and in biofilm, respectively. FICI
      values were from 0.375 to 1.25 when in suspension and from 0.25 to 1.25 when in
      biofilm. CONCLUSIONS:   Synergistic activity of harmaline and CHG against
      clinical isolates of S. aureus (in suspension and in biofilm) was observed in
      vitro. SIGNIFICANCE AND IMPACT OF THE STUDY:   This study might provide
      alternative methods to overcome the problem of drug-resistance of S. aureus both
      in suspension and in biofilm.

PMID- 22394165
TI  - The architectural organization of human stem cell cycle regulatory machinery.
AB  - Two striking features of human embryonic stem cells that support biological
      activity are an abbreviated cell cycle and reduced complexity to nuclear
      organization. The potential implications for rapid proliferation of human
      embryonic stem cells within the context of sustaining pluripotency, suppressing
      phenotypic gene expression and linkage to simplicity in the architectural
      compartmentalization of regulatory machinery in nuclear microenvironments is
      explored. Characterization of the molecular and architectural commitment steps
      that license human embryonic stem cells to initiate histone gene expression is
      providing understanding of the principal regulatory mechanisms that control the
      G1/S phase transition in primitive pluripotent cells. From both fundamental
      regulatory and clinical perspectives, further understanding of the pluripotent
      cell cycle in relation to compartmentalization of regulatory machinery in nuclear
      microenvironments is relevant to applications of stem cells for regenerative
      medicine and new dimensions to therapy where traditional drug discovery
      strategies have been minimally effective.

PMID- 22394167
TI  - Targeting the cancer initiating cell: the ultimate target for cancer therapy.
AB  - An area of therapeutic interest in cancer biology and treatment is targeting the
      cancer stem cell, more appropriately referred to as the cancer initiating cell
      (CIC). CICs comprise a subset of hierarchically organized, rare cancer cells with
      the ability to initiate cancer in xenografts in genetically modified murine
      models. CICs are thought to be responsible for tumor onset, self
      renewal/maintenance, mutation accumulation and metastasis. CICs may lay dormant
      after various cancer therapies which eliminate the more rapidly proliferating
      bulk cancer (BC) mass. However, CICs may remerge after therapy is discontinued as
      they may represent cells which were either intrinsically resistant to the
      original therapeutic approach or they have acquired mutations which confer
      resistance to the primary therapy. In experimental mouse tumor transplant models,
      CICs have the ability to transfer the tumor to immunocompromised mice very
      efficiently while the BCs are not able to do so as effectively. Often CICs
      display increased expression of proteins involved in drug resistance and hence
      they are intrinsically resistant to many chemotherapeutic approaches.
      Furthermore, the CICs may be in a suspended state of proliferation and not
      sensitive to common chemotherapeutic and radiological approaches often employed
      to eliminate the rapidly proliferating BCs. Promising therapeutic approaches
      include the targeting of certain signal transduction pathways (e.g., RAC, WNT,
      PI3K, PML) with small molecule inhibitors or targeting specific cell-surface
      molecules (e.g., CD44), with effective cytotoxic antibodies. The existence of
      CICs could explain the high frequency of relapse and resistance to many currently
      used cancer therapies. New approaches should be developed to effectively target
      the CIC which could vastly improve cancer therapies and outcomes. This review
      will discuss recent concepts of targeting CICs in certain leukemia models.

PMID- 22394168
TI  - Affective states leak into movement execution: automatic avoidance of threatening
      stimuli in fear of spider is visible in reach trajectories.
AB  - Approach-like actions are initiated faster with stimuli of positive valence.
      Conversely, avoidance-like actions are initiated faster with threatening stimuli
      of negative valence. We went beyond reaction time measures and investigated
      whether threatening stimuli also affect the way in which an action is carried
      out. Participants moved their hand either away from the picture of a spider
      (avoidance) or they moved their hand toward the picture of a spider (approach).
      We compared spider-fearful participants to non-anxious participants. When
      reaching away from the threatening spider picture, spider-fearful participants
      moved more directly to the target than controls. When reaching toward the
      threatening spider, spider-fearful participants moved less directly to the target
      than controls. Some conditions that showed clear differences in movement
      trajectories between spider-fearful and control participants were devoid of
      differences in reaction time. The deviation away from threatening stimuli
      provides evidence for the claim that affective states like fear leak into
      movement programming and produce deviations away from threatening stimuli in
      movement execution. Avoidance of threatening stimuli is rapidly integrated into
      ongoing motor behaviour in order to increase the distance between the
      participant's body and the threatening stimulus.

PMID- 22394169
TI  - Fallopian tube metastases of non-gynaecological origin: a series of 20 cases
      emphasizing patterns of involvement including intra-epithelial spread.
AB  - AIMS:   To determine the frequency and distribution of Fallopian tube involvement
      in patients with ovarian metastases of non-gynaecological origin. METHODS AND
      RESULTS:   All Fallopian tube tissue was processed for histological examination
      in a consecutive series of 31 patients with ovarian metastases of non
      gynaecological origin. The most common primary sites were appendix (n = 10) colon
      (n = 7), stomach (n = 6) and breast (n = 4). Twenty cases (65%) showed at least
      one type of tubal spread. Mural involvement was most common (14 cases) but
      serosal, intra-vascular, intra-epithelial and intra-lumenal spread were also
      identified in 12, 9, 8 and 11 cases respectively. Intra-epithelial involvement
      was restricted to the fimbrial epithelium and mimicked tubal carcinoma in situ
      (CIS) architecturally. Pagetoid invasion was noted in two of the cases.
      CONCLUSIONS:   The Fallopian tubes are commonly involved in patients who have
      neoplasms metastatic to the ovaries. Metastases may show a CIS-like pattern of
      intra-epithelial spread and therefore small serous CIS-type lesions may not
      represent proof of tubal tumour origin in patients who have high-stage pelvic
      serous carcinomas. The frequency of intra-lumenal tumour cells supports
      transtubal spread as a likely mechanism for mucosal involvement by metastatic
      tumours involving the lower genital tract.

PMID- 22394171
TI  - Editorial: B lymphocytes as programmers and effectors of immunity, their roles
      beyond antibody production.

PMID- 22394170
TI  - No effects of n-3 fatty acid supplementation on serum total testosterone levels
      in older men: the Alpha Omega Trial.
AB  - The intake of the n-3 fatty acids alpha-linolenic acid (ALA), acid (EPA) and
      docosahexaenoic acid (DHA) has been related to testosterone levels in
      epidemiological analyses. The aim of this study was to assess whether the n-3
      fatty acids affects testosterone levels in post-myocardial infarction (MI)
      patients, who are at risk of testosterone deficiency. In a double-blind, placebo
      controlled trial of low-dose supplementation of n-3 fatty acids, we included 1850
      male post-MI patients aged 60-80 years who participated in the Alpha Omega Trial.
      Patients were randomly allocated to margarines that provided 400 mg/day of EPA
      DHA (n = 453), 2 mg/day of ALA (n = 467), EPA-DHA plus ALA (n = 458), or placebo
      (n = 472). Serum testosterone levels were assessed at baseline and after 41
      months using whole day blood samples obtained at the subjects' home or at the
      hospital. Subjects were on average age of 68.4 (SD 5.3) years old and had
      baseline mean serum total testosterone of 14.8 (SD 5.6) nmol/L. The four
      randomized groups did not differ for baseline characteristics. ALA, EPA-DHA, and
      EPA-DHA plus ALA supplementation did not affect serum total testosterone compared
      to placebo. Moreover, n-3 fatty acid supplementation did not affect the risk of
      incident testosterone deficiency (n = 76 with total testosterone <8.0 nmol/L). We
      conclude that n-3 fatty acids supplementation did not affect serum total
      testosterone in men who had had a MI.

PMID- 22394172
TI  - B cells: programmers of CD4 T cell responses.
AB  - B cells are once again gaining prominence as important programmers of CD4 T cell
      responses. With widespread use of B cell depletion therapy in the clinic, proving
      effective in treating diseases previously considered T cell-mediated, the time is
      right for a re-appraisal of the B cell. Though typically considered weak, Th2
      driving APC, it is now clear that they are necessary for a robust and long-lived
      CD4 T cell response in many settings. The sphere of B cell influence extends well
      beyond that of simply antibody production; antigen presentation, cytokine
      secretion, costimulation and development of lymphoid tissue architecture are all
      critical aspects of B cell immunobiology, the absence of which has serious
      impacts for T cell priming and memory. The aim of this review is to look at non
      antibody mediated B cell function and to ask how, where and when do B cells
      influence the CD4 T cell response?

PMID- 22394173
TI  - Unraveling effector functions of B cells during infection: the hidden world
      beyond antibody production.
AB  - Antibodies made by B cells are critically important for immune protection to a
      variety of infectious agents. However, it is becoming increasingly clear that B
      cells do more than make antibodies and that B cells can both enhance and suppress
      immune responses. Furthermore, there is growing evidence that B cells modulate
      cellular immune responses by antibody dependent and independent mechanisms.
      Although we have a good understanding of the roles played by antibody- secreting
      effector B cells during immune responses, we know very little about the Ab
      independent "effector" functions of B cells in either health or disease. Given
      the recent data suggesting that B cells may contribute to autoimmune disease
      pathogenesis via an antibody independent mechanism and the increasing use of B
      cell depletion therapy in autoimmune patients, investigators are beginning to
      reassess the multiple roles for B cells during immune responses. In this article,
      we review data describing how B cells mediate protection to pathogens
      independently of antibody production. In particular, we will focus on the role
      that B cells play in facilitating dendritic cell and T cell interactions in lymph
      nodes, the importance of antigen-presenting B cells in sustaining effector T cell
      and T follicular helper responses to pathogens and the relevance of cytokine
      producing effector and regulatory B cells in immune responses.

PMID- 22394175
TI  - Role of inhibitory BCR co-receptors in immunity.
AB  - B lymphocytes (B cells) express a variety of membrane molecules containing
      immunoreceptor tyrosine-based inhibition motifs (ITIMs) in the cytoplasmic region
      such as FcgammaRIIB, FCRLs, CD22, mouse Siglec-G/human Siglec-10, PECAM-1, mouse
      PIR-B/human LIRB1 and LIRB2PD-1 and CD72. When phosphorylated, ITIMs in these
      molecules recruit and activate phosphatases such as SH2 domain-containing protein
      tyrosine phosphatase 1 (SHP-1), SHP-2, SH2 domain- containing inositol 5
      phosphatase 1 (SHIP1) and SHIP2 depending on receptors. These phosphatases then
      negatively regulate B cell antigen receptor (BCR) signaling. Because of their
      ability to inhibit BCR signaling, these ITIMcontaining molecules are called
      inhibitory BCR co-receptors. Studies on mice deficient in an inhibitory co
      receptor have demonstrated that the inhibitory co-receptors regulate B cell
      development, antibody responses and development of autoimmune diseases. Moreover,
      polymorphisms in some inhibitory co-receptors such as FcgammaRIIB, FCRL3 and CD72
      are associated with autoimmune diseases, suggesting a crucial role of inhibitory
      co-receptor polymorphisms in the regulation of autoimmune diseases. The ligands
      for inhibitory co-receptors regulate their inhibitory activity by inducing co
      ligation of the co-receptors with BCR or some other regulatory mechanisms.
      Inhibitory co-receptors and their ligands are therefore good targets for
      controlling antibody responses and autoimmune diseases.

PMID- 22394166
TI  - Neural stem cell niches in health and diseases.
AB  - Presence of neural stem cells in adult mammalian brains, including human, has
      been clearly demonstrated by several studies. The functional significance of
      adult neurogenesis is slowly emerging as new data indicate the sensitivity of
      this event to several "every day" external stimuli such as physical activity,
      learning, enriched environment, aging, stress and drugs. In addition,
      neurogenesis appears to be instrumental for task performance involving complex
      cognitive functions. Despite the growing body of evidence on the functional
      significance of NSC and despite the bulk of data concerning the molecular and
      cellular properties of NSCs and their niches, several critical questions are
      still open. In this work we review the literature describing i) old and new sites
      where NSC niche have been found in the CNS; ii) the intrinsic factors regulating
      the NSC potential; iii) the extrinsic factors that form the niche
      microenvironment. Moreover, we analyse NSC niche activation in iv) physiological
      and v) pathological conditions. Given the not static nature of NSCs that
      continuously change phenotype in response to environmental clues, a unique
      "identity card" for NSC identification is still lacking. Moreover, the multiple
      location of NSC niches that increase in diseases, leaves open the question of
      whether and how these structures communicate throughout long distance. We propose
      a model where all the NSC niches in the CNS may be connected in a functional
      network using the threads of the meningeal net as tracks.

PMID- 22394174
TI  - Evolutionary and functional relationships of B cells from fish and mammals:
      insights into their novel roles in phagocytosis and presentation of particulate
      antigen.
AB  - The evolutionary origins of Ig-producing B cells appear to be linked to the
      emergence of fish in this planet. There are three major classes of living fish
      species, which from most primitive to modern they are referred to as agnathan
      (e.g., lampreys), Chondrichthyes (e.g., sharks), and teleost fish (e.g., rainbow
      trout). Agnathans do not have immunoglobulin- producing B cells, however these
      fish contain a subset of lymphocytes-like cells producing type B variable
      lymphocyte receptors (VLRBs) that appear to act as functional analogs of
      immunoglobulins. Chondrichthyes fish represent the most primitive living species
      containing bona-fide immunoglobulin-producing B cells. Their B cells are known to
      secrete three types of antibodies, IgM, IgW and IgNAR. Teleost fish are also
      called bony fish since they represent the most ancient living species containing
      true bones. Teleost B cells produce three different immunoglobulin isotypes, IgM,
      IgD and the recently described IgT. While teleost IgM is the principal player in
      systemic immunity, IgT appears to be a teleost immunoglobulin class specialized
      in mucosal immune responses. Thus far, three major B cell lineages have been
      described in teleost, those expressing either IgT or IgD, and the most common
      lineage which co-expresses IgD and IgM. A few years ago, the study of teleost
      fish B cells revealed for the first time in vertebrates the existence of B cell
      subsets with phagocytic and intracellular bactericidal capacities. This finding
      represented a paradigm shift as professional phagocytosis was believed to be
      exclusively performed by some cells of the myeloid lineage (i.e., macrophages,
      monocytes, neutrophils). This phagocytic capacity was also found in amphibians
      and reptiles, suggesting that this innate capacity was evolutionarily conserved
      in certain B cell subsets of vertebrates. Recently, the existence of subsets of B
      cells with phagocytic and bactericidal abilities have also been confirmed in
      mammals. Moreover, it has been shown that phagocytic B-1 B cells have a potent
      ability to present particulate antigen to CD4+ T cells. Thus, studies carried out
      originally on fish B cells have lead to the discovery of new innate and adaptive
      roles of B cells in mammals. This review will concentrate on the evolutionary and
      functional relationships of fish and mammalian B cells, focusing mainly on the
      newly discovered roles of these cells in phagocytosis, intracellular killing and
      presentation of particulate antigen.

PMID- 22394177
TI  - Functional interactions between B lymphocytes and the innate immune system.
AB  - The immune system is composed of multiple cell types, which together improve the
      resistance of the organism against infections. The unfolding of a successful host
      response ensuring effective protection against pathogens requires an appropriate
      coordination of the different players of the immune system. Innate cells and T
      cells extensively communicate during immune reactions, providing multiple
      opportunities for the mutual coordination of these two defense pathways. Little
      is known about the functional interactions between B and innate cells, and it is
      generally assumed that they influence each other indirectly through effects on T
      cells. However, recent studies highlighted important roles for innate cells in
      initial presentation of antigen to B cells after immunization, and in long-term
      maintenance of antibody-producing cells in bone marrow after resolution of immune
      responses. Furthermore, it was found that activated B cells could regulate the
      activity of innate cells through production of cytokines. Here, we review how
      direct interactions between innate and B cells can contribute to orchestration of
      humoral and cellular immunity.

PMID- 22394176
TI  - Reprogramming of B cells into regulatory cells with engineered fusokines.
AB  - B cells play a pivotal role in host adaptive immunity against pathogenic
      microorganisms, but may also maladaptively contribute to the pathogenesis of
      autoimmune diseases. In contrast, distinct B cell subsets have the capacity to
      regulate host immune response, and suppress inflammation. B regulatory cells are
      a rare population of endogenous Blymphocytes defined in part by production of the
      anti-inflammatory cytokine IL-10. Although "natural" B regulatory cells exist in
      vivo, the low frequency of B regulatory cells may be a limiting factor on their
      impact in autoimmune ailments. In answer to this unmet need, we have developed a
      novel strategy for alternate lymphoid activation: fusokines. These wholly
      engineered chimeric leukines fuse two functionally unrelated cytokines for the
      purpose of alternate immune modulation. The GM-CSF- and IL-15-derived fusokine:
      GIFT15, possesses entirely novel and unheralded immune modulating properties
      mediated through the IL15 receptor which reprograms naive B cells into B
      regulatory cells (Bregs). In this article, we review the current approaches to
      generate Bregs in vitro, and highlight gain-of-function mechanisms by which
      GIFT15- induced Bregs abrogate pathogenic autoimmunity in mice. We also
      demonstrate that the human equivalent of inducible Bregs may also serve as a new
      potent therapeutic tool for treatment of autoimmune disease.

PMID- 22394178
TI  - B-cell based gene therapy for autoimmune diseases.
AB  - The essence of the adaptive immune system is self tolerance, which is maintained
      by various central and peripheral check points. However, the tolerance mechanisms
      can be broken in autoimmune disease conditions due to genetic predisposition and
      environmental triggers. As a consequence, a patient's tissue is attacked by
      his/her own adaptive immune system. An ideal therapy for autoimmune diseases
      should include methods to re-establish tolerance to the underpinning
      autoantigen(s). During the last 15 years our lab has been dedicated to developing
      a novel B-cell gene therapy approach for antigen-specific tolerance induction.
      This approach has been successfully applied to at least five different animal
      models for human autoimmune diseases. In this article, we will discuss many of
      our successful preclinical studies using the B-cell gene therapy approach to
      induce tolerance, as well as similar studies from others. Particular focus will
      be given to the tolerance induction mechanisms that have been revealed from these
      studies.

PMID- 22394179
TI  - Primary and secondary B-cell responses to pulmonary virus infection.
AB  - Viruses form particulate structures possessing high-density B-cell epitopes and
      viral RNA/DNA, which are ligands for multiple Toll-like receptors (TLRs). B cells
      are able to sense these viral antigenic signatures through B-cell antigen
      receptors (BCRs) and TLRs, both of which synergistically shape the magnitude and
      quality of virus-specific B-cell responses. In many viruses, B-cell recognition
      of these virus signatures is often hampered by tissue tropisms toward nonlymphoid
      organs. However, ectopic localizations of B cells at virus replication sites
      facilitate the efficient recognition of intact virus particles. Following
      pulmonary infection by influenza virus, virus-specific B-cell responses occur in
      the tertiary lymphoid organs of lungs near the sites of virus replication as well
      as in the draining lymph nodes. Lungs then begin to support the germinal center
      response and the formation of niches for plasma cells and memory B cells, thus
      potentiating B-cell intrinsic recognition of virus particles at these sites. In
      this review, we discuss how the anatomical location and virus- sensing properties
      of B cells coordinate protective B-cell responses against pulmonary virus
      infection.

PMID- 22394180
TI  - Towards the standardisation of the neuroblastoma (neuro-2a) cell-based assay for
      ciguatoxin-like toxicity detection in fish: application to fish caught in the
      Canary Islands.
AB  - The ouabain/veratridine-dependent neuroblastoma (neuro-2a) cell-based assay (CBA)
      was applied for the determination of the presence of ciguatoxin (CTX)-like
      compounds in ciguatera-suspected fish samples caught in the Canary Islands. In
      order to avoid matrix interferences the maximal concentration of wet weight fish
      tissue exposed to the neuro-2a cells was set at 20 mg tissue equivalent (TE) ml(
      1) according to the sample preparation procedure applied. In the present study,
      the limit of quantification (LOQ) of CTX1B equivalents in fish extract was set at
      the limit of detection (LOD), being defined as the concentration of CTX1B
      equivalents inhibiting 20% cell viability (IC(20)). The LOQ was estimated as
      0.0096 ng CTX1B eq.g TE(-1) with 23-31% variability between experiments. These
      values were deemed sufficient even though quantification given at the IC(50) (the
      concentration of CTX1B equivalents inhibiting 50% cell viability) is more
      accurate with a variability of 17-19% between experiments. Among the 13 fish
      samples tested, four fish samples were toxic to the neuro-2a cells with
      estimations of the content in CTX1B g(-1) of TE ranging from 0.058 (+/- 0.012) to
      6.23 (+/- 0.713) ng CTX1B eq.g TE(-1). The high sensitivity and specificity of
      the assay for CTX1B confirmed its suitability as a screening tool of CTX-like
      compounds in fish extracts at levels that may cause ciguatera fish poisoning.
      Species identification of fish samples by DNA sequence analysis was conducted in
      order to confirm tentatively the identity of ciguatera risk species and it
      revealed some evidence of inadvertent misidentification. Results presented in
      this study are a contribution to the standardisation of the neuro-2a CBA and to
      the risk analysis for ciguatera in the Canary Islands.

PMID- 22394181
TI  - Electrochemical behavior of chlorogenic acid at a boron-doped diamond electrode
      and estimation of the antioxidant capacity in the coffee samples based on its
      oxidation peak.
AB  - In this study, an electroanalytical methodology for the determination of
      chlorogenic acid (CGA) was achieved at a boron-doped diamond electrode under
      adsorptive transfer stripping voltammetric conditions. The values obtained for
      CGA were used to estimate the antioxidant properties of the coffee sample based
      on CGA oxidation. By using square-wave stripping mode, the compound yielded a
      well-defined voltammetric response at +0.49 V with respect to Ag/AgCl in Britton
      Robinson buffer at pH 3.0 (after 120 s accumulations at a fixed potential of 0.40
      V). At the optimum experimental conditions, linear calibration curve is obtained
      within the concentration range of 0.25 to 4.0 MUg mL-1 with the limit of
      detection 0.049 MUg mL-1 . The developed protocol was successfully applied for
      the analysis of antioxidant capacity in the coffee products such as Turkish
      coffee and instant coffee.

PMID- 22394182
TI  - Cell therapy for skin wound using fibroblast encapsulated poly(ethylene glycol)
      poly(L-alanine) thermogel.
AB  - As a new application of a thermogel, a poly(ethylene glycol)-b-poly(L-alanine)
      (PEG-L-PA) gel encapsulating fibroblasts was investigated for wound healing. The
      fibroblasts were encapsulated by the temperature sensitive sol-to-gel transition
      of the polymer aqueous solution. Under the in vitro three-dimensional (3D) cell
      culture condition, the PEG-L-PA thermogel was comparable with Matrigel for cell
      proliferation and was significantly better than Matrigel for collagen types I and
      III formation. After confirming the excellent 3D microenvironment of the PEG-L-PA
      thermogel for fibroblasts, in vivo wound healing was investigated by injecting
      the cell-suspended polymer aqueous solution on incisions of rat skin, where the
      cell-encapsulated gel was formed in situ. Compared with the phosphate buffered
      saline treated system and the cell-free PEG-L-PA thermogel, the cell-encapsulated
      PEG-L-PA thermogel not only accelerated the wound closure but also improved
      epithelialization and the formation of skin appendages such as keratinocyte layer
      (epidermis), hair follicles, and sebaceous glands. The results demonstrate the
      potential of thermogels for cell therapy as an injectable tissue-engineering
      scaffold.

PMID- 22394184
TI  - Redox nanoparticle treatment protects against neurological deficit in focused
      ultrasound-induced intracerebral hemorrhage.
AB  - BACKGROUND: Intracerebral hemorrhage is reported to induce the generation of
      reactive oxygen species and oxidative DNA damage in the brain. AIMS: We aimed to
      examine whether our designed redox polymer nanoparticle could reduce
      intracerebral hemorrhage induced by 1-MHz focused ultrasound sonication coupled
      with microbubble treatment. MATERIALS & METHODS: Contrast-enhanced ultrasound
      imaging, frozen section, brain edema, neurologic deficit, the number of
      morphologically normal neurons, DNA oxidization and superoxide anion generation
      were used to investigate the neuroprotective effect of redox polymer
      nanoparticles. RESULTS: We confirmed that the 1-MHz focused ultrasound coupled
      with microbubble produced intracerebral hemorrhage and showed that the redox
      polymer nanoparticle ameliorates intracerebral hemorrhage-induced brain edema,
      neurological deficit and oxidative damage. CONCLUSION: These results suggest that
      redox polymer nanoparticle is a potential therapeutic agent for intracerebral
      hemorrhage induced by focused ultrasound.

PMID- 22394185
TI  - Controlled drug delivery from composites of nanostructured porous silicon and
      poly(L-lactide).
AB  - AIMS: Porous silicon (pSi) and poly(L-lactide) (PLLA) both display good
      biocompatibility and tunable degradation behavior, suggesting that composites of
      both materials are suitable candidates as biomaterials for localized drug
      delivery into the human body. The combination of a pliable and soft polymeric
      material with a hard inorganic porous material of high drug loading capacity may
      engender improved control over degradation and drug release profiles and be
      beneficial for the preparation of advanced drug delivery devices and
      biodegradable implants or scaffolds. MATERIALS & METHODS: In this work, three
      different pSi and PLLA composite formats were prepared. The first format involved
      grafting PLLA from pSi films via surface-initiated ring-opening polymerization
      (pSi-PLLA [grafted]). The second format involved spin coating a PLLA solution
      onto oxidized pSi films (pSi-PLLA [spin-coated]) and the third format consisted
      of a melt-cast PLLA monolith containing dispersed pSi microparticles (pSi-PLLA
      [monoliths]). The surface characterization of these composites was performed via
      infrared spectroscopy, scanning electron microscopy, atomic force microscopy and
      water contact angle measurements. The composite materials were loaded with a
      model cytotoxic drug, camptothecin (CPT). Drug release from the composites was
      monitored via fluorimetry and the release profiles of CPT showed distinct
      characteristics for each of the composites studied. RESULTS: In some cases,
      controlled CPT release was observed for more than 5 days. The PLLA spin coat on
      pSi and the PLLA monolith containing pSi microparticles both released a CPT
      payload in accordance with the Higuchi and Ritger-Peppas release models.
      Composite materials were also brought into contact with human lens epithelial
      cells to determine the extent of cytotoxicity. CONCLUSION: We observed that all
      the CPT containing materials were highly efficient at releasing bioactive CPT,
      based on the cytotoxicity data.

PMID- 22394183
TI  - Interaction of cowpea mosaic virus nanoparticles with surface vimentin and
      inflammatory cells in atherosclerotic lesions.
AB  - AIMS: Detection of atherosclerosis has generally been limited to the late stages
      of development, after cardiovascular symptoms present or a clinical event occurs.
      One possibility for early detection is the use of functionalized nanoparticles.
      The aim of this study was the early imaging of atherosclerosis using
      nanoparticles with a natural affinity for inflammatory cells in the lesion.
      MATERIALS & METHODS: We investigated uptake of cowpea mosaic virus by macrophages
      and foam cells in vitro and correlated this with vimentin expression. We also
      examined the ability of cowpea mosaic virus to interact with atherosclerotic
      lesions in a murine model of atherosclerosis. RESULTS & CONCLUSION: We found that
      uptake of cowpea mosaic virus is increased in areas of atherosclerotic lesion.
      This correlated with increased surface vimentin in the lesion compared with
      nonlesion vasculature. In conclusion, cowpea mosaic virus and its vimentin
      binding region holds potential for use as a targeting ligand for early
      atherosclerotic lesions, and as a probe for detecting upregulation of surface
      vimentin during inflammation.

PMID- 22394186
TI  - Ultrasensitive nanostructured immunosensor for stem and carcinoma cell
      pluripotency gatekeeper protein NANOG.
AB  - AIMS: To develop an immunosensor for ultrasensitive detection of the NANOG
      protein. NANOG regulates pluripotency in stem cells and some cancer cells. This
      article reports the first electrochemical immunosensor for ultrasensitive
      detection and absolute quantification of the NANOG protein. The sensor features
      dense capture antibody-coated gold nanoparticle layers on a pyrolytic graphite
      underlayer. MATERIALS & METHODS: Two separate multilabel detection strategies
      were used to achieve moderate and ultra-high sensitivity. RESULTS: Good
      sensitivity was achieved for NANOG over the concentration range 0.1-160 pg/ml.
      The moderate-sensitivity approach gave a detection limit of 25 pg/ml, while the
      ultrasensitive method achieved a 250-fold lower detection limit of 0.1 pg/ml.
      Amounts of NANOG detected in human embryonic stem cell lysates correlated well
      with qualitative western blots and mRNA expression. CONCLUSION: The
      electrochemical gold nanoparticle immunosensor is suitable for measuring NANOG
      protein expression in stem and carcinoma cell tissue lysates at very low levels.

PMID- 22394187
TI  - Cell differentiation and osseointegration influenced by nanoscale anodized
      titanium surfaces.
AB  - AIMS: We aimed to study the interactions between human mesenchymal stem cells and
      the bone integration of nanostructured titanium implants. MATERIALS & METHODS:
      Nanopores of 20, 30 and 50 nm were prepared by anodization of titanium at 5, 10
      and 20 V in a mixture of fluorhydric and acetic acid. Ti 30 and 50 nanostructures
      promoted early osteoblastic gene differentiation of the human mesenchymal stem
      cells without osteogenic supplements. The osseointegration of nanostructured and
      control titanium implants was compared by implantation in rat tibias for 1 and 3
      weeks. RESULTS: The nanostructures significantly accelerated bone apposition and
      bone bonding strength in vivo in correlation with in vitro results. CONCLUSION:
      These findings demonstrate that specific nanostructures controlled the
      differentiation of cells and, thus, the integration of implants in tissues. These
      nanoporous titanium surfaces may be of considerable interest for dental and
      orthopedic implants.

PMID- 22394188
TI  - High-pressure freezing/freeze substitution and transmission electron microscopy
      for characterization of metal oxide nanoparticles within sunscreens.
AB  - AIMS: To date, the description of a single, suitable method to observe in detail
      metal oxide nanoparticles in situ within sunscreens is currently lacking, despite
      growing concern as to how they interact with humans. This study explores the
      usefulness of transmission electron microscopy to characterize the nanoparticles
      in sunscreens. MATERIALS & METHODS: High-pressure freezing then freeze
      substitution was used to prepare resin-embedded commercial sunscreen samples, and
      ultrathin sections of these were observed with transmission electron microscopy.
      Conventional room temperature processing for resin embedding was also trialed.
      RESULTS: High-pressure frozen/freeze substituted samples provided clear
      visualization of the size and shape of the nanoparticles and agglomerates and
      allowed further characterization of the composition and crystal form of the metal
      oxides, while conventionally processed chemically fixed samples were subject to
      distribution/agglomeration artifacts. CONCLUSION: Transmission electron
      microscopy of high-pressure frozen/freeze substituted samples is an ideal method
      to completely observe metal oxide nanoparticles in situ in sunscreens.

PMID- 22394189
TI  - Electrocatalytic oxygen reduction by iron tetra-arylporphyrins bearing pendant
      proton relays.
AB  - Iron(III) meso-tetra(2-carboxyphenyl)porphine chloride (1) was investigated as a
      soluble electrocatalyst for the oxygen reduction reaction (ORR) in acetonitrile
      with [H(DMF)(+)]OTf(-). Rotating ring-disk voltammetry, spectroelectrochemistry,
      and independent reactions with hydrogen peroxide indicate that 1 has very high
      selectivity for reduction of O(2) to H(2)O, without forming significant amounts
      of H(2)O(2). Cyclic voltammetric measurements at high substrate/catalyst ratios
      (high oxygen pressure) allowed the estimation of a turnover frequency (TOF) of
      200 s(-1) at -0.4 V vs Cp(2)Fe(+/0). This is, to our knowledge, the first
      reported TOF for a soluble ORR electrocatalyst under kinetically controlled
      conditions. The 4-carboxyphenyl isomer of 1, in which the carboxylic acids point
      away from the iron center, is a much less selective catalyst. This comparison
      shows that carboxylate groups positioned to act as proton delivery relays can
      substantially enhance the selectivity of ORR catalysis.

PMID- 22394190
TI  - Vancomycin modulated autolysis in Staphylococcus aureus: does it vary with the
      susceptibility and planktonic or biofilm phenotype?

PMID- 22394191
TI  - Pediatric anaplastic lymphoma kinase-positive large B-cell lymphoma: a case
      report and review of the literature.
AB  - We present a case of pediatric anaplastic lymphoma kinase-positive large B-cell
      lymphoma (ALK-positive LBCL) with a cervical, mesentery, and pelvis cavity mass.
      Histologic examination of the cervical mass revealed that the lesion was composed
      of diffuse large immunoblastic-like or plasmablastic-like tumor cells with a
      sinusoidal growth pattern. The tumor cells were strongly immunoreactive for ALK;
      revealed a granular cytoplasmic distribution; and were diffusely positive for
      CD45, CD4, CD138, epithelial membrane antigen, and multiple myeloma oncogene-1
      but negative for CD20 and CD79a. The patient underwent 5 courses of
      cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposid and obtained
      a remarkable clinical response with regression of mesentery and pelvis cavity
      mass. We suggest that this distinct subtype of large B-cell lymphoma should
      belong to the spectrum of pediatric lymphomas and that radiologic examination
      should be performed to inspect the progression of disease even if the patients
      experienced complete remission at initial chemotherapy.

PMID- 22394192
TI  - beta-Nitro derivatives of iron corrolates.
AB  - Two different methods for the regioselective nitration of different meso
      triarylcorroles leading to the corresponding beta-substituted nitrocorrole iron
      complexes have been developed. A two-step procedure affords three Fe(III)
      nitrosyl products-the unsubstituted corrole, the 3-nitrocorrole, and the 3,17
      dinitrocorrole. In contrast, a one-pot synthetic approach drives the reaction
      almost exclusively to formation of the iron nitrosyl 3,17-dinitrocorrole.
      Electron-releasing substituents on the meso-aryl groups of the triarylcorroles
      induce higher yields and longer reaction times than what is observed for the
      synthesis of similar triarylcorroles with electron-withdrawing functionalities,
      and these results can be confidently attributed to the facile formation and
      stabilization of an intermediate iron corrole pi-cation radical. Electron
      withdrawing substituents on the meso-aryl groups of triarylcorrole also seem to
      labilize the axial nitrosyl group which, in the case of the
      pentafluorophenylcorrole derivative, results in the direct formation of a
      disubstituted iron MU-oxo dimer complex. The influence of meso-aryl substituents
      on the progress and products of the nitration reaction was investigated. In
      addition, to elucidate the most important factors which influence the redox
      reactivity of these different iron nitrosyl complexes, selected compounds were
      examined by cyclic voltammetry and thin-layer UV-visible or FTIR
      spectroelectrochemistry in CH(2)Cl(2).

PMID- 22394193
TI  - On "sex trafficking and the exploitation of adolescents".

PMID- 22394194
TI  - Stability and structure of protein-lipoamino acid colloidal particles: toward
      nasal delivery of pharmaceutically active proteins.
AB  - To circumvent the painful intravenous injection of proteins in the treatment of
      children with growth deficiency, anemia, and calcium insufficiency, we
      investigated the stability and structure of protein-lipoamino acid complexes that
      could be nasally sprayed. Preparations that ensure a colloidal and structural
      stability of recombinant human growth hormone (rhGH), recombinant human
      erythropoietin (rhEPO), and salmon calcitonin (sCT) mixed with lauroyl proline
      (LP) were established. Protein structure was controlled by circular dichroism,
      and very small sizes of ca. 5 nm were determined by dynamic light scattering. The
      colloidal preparations could be sprayed with a droplet size of 20-30 MUm. The
      molecular structure of aggregates was investigated by all-atom molecular
      dynamics. Whereas a lauroyl proline capping of globular proteins rhGH and rhEPO
      with preservation of their active structure was observed, a mixed micelle of sCT
      and lipoamino acids was formed. In the latter, aggregated LP constitutes the
      inner core and the surface is covered with calcitonins that acquire a marked
      alpha-helix character. Hydrophobic/philic interaction balance between proteins
      and LP drives the particles' stability. Passage through nasal cells grown at
      confluence was markedly increased by the colloidal preparations and could reach a
      20 times increase in the case of EPO. Biological implications of such colloidal
      preparations are discussed in terms of furtiveness.

PMID- 22394195
TI  - Inhibition of hepatitis C virus NS3 helicase by manoalide.
AB  - The hepatitis C virus (HCV) causes one of the most prevalent chronic infectious
      diseases in the world, hepatitis C, which ultimately develops into liver cancer
      through cirrhosis. The NS3 protein of HCV possesses nucleoside triphosphatase
      (NTPase) and RNA helicase activities. As both activities are essential for viral
      replication, NS3 is proposed as an ideal target for antiviral drug development.
      In this study, we identified manoalide (1) from marine sponge extracts as an RNA
      helicase inhibitor using a high-throughput screening photoinduced electron
      transfer (PET) system that we previously developed. Compound 1 inhibits the RNA
      helicase and ATPase activities of NS3 in a dose-dependent manner, with IC(50)
      values of 15 and 70 MUM, respectively. Biochemical kinetic analysis demonstrated
      that 1 does not affect the apparent K(m) value (0.31 mM) of NS3 ATPase activity,
      suggesting that 1 acts as a noncompetitive inhibitor. The binding of NS3 to
      single-stranded RNA was inhibited by 1. Manoalide (1) also has the ability to
      inhibit the ATPase activity of human DHX36/RHAU, a putative RNA helicase. Taken
      together, we conclude that 1 inhibits the ATPase, RNA binding, and helicase
      activities of NS3 by targeting the helicase core domain conserved in both HCV NS3
      and DHX36/RHAU.

PMID- 22394196
TI  - Expression profiling of starchy endosperm metabolic proteins at 21 stages of
      wheat grain development.
AB  - Proteomic analysis of albumins and globulins (alg) present in starchy endosperm
      of wheat (Triticum aestivum cv Recital), at 21 stages of grain development, led
      to the identification of 487 proteins. Four main developmental phases of these
      metabolic proteins, with three subphases in phase three and two in phase four,
      were shown. Hierarchical cluster analysis revealed nine major expression profiles
      throughout grain development. Classification of identified proteins in 17
      different biochemical functions provided a uniform picture of temporal
      coordination among cellular processes. Proteins involved in cell division,
      transcription/translation, ATP interconversion, protein synthesis, protein
      transport, along with amino acid, lipid, carbohydrate and nucleotide metabolisms
      were highly expressed in early and early mid stages of development. Protein
      folding, cytoskeleton, and storage proteins peaked during the middle of grain
      development, while in later stages stress/defense, folic acid metabolism, and
      protein turn over were the abundant functional categories. Detailed analysis of
      stress/defense enzymes revealed three different evolutionary profiles. A global
      map with their predicted subcellular localizations and placement in grain
      developmental scale was constructed. The present study of complete grain
      development enriched our knowledge on proteome expression of alg, successively
      from endosperm cell division and differentiation to programmed cell death.

PMID- 22394197
TI  - Palladium-catalyzed N-arylation of 2-aminothiazoles.
AB  - A method for the Pd-catalyzed coupling of 2-aminothiazole derivatives with aryl
      bromides and triflates is described. Significantly, for this class of
      nucleophiles, the coupling exhibits a broad substrate scope and proceeds with a
      reasonable catalyst loading. Furthermore, an interesting effect of acetic acid as
      an additive is uncovered that facilitates catalyst activation.

PMID- 22394198
TI  - In vitro antimalarial activity and molecular docking analysis of 4-aminoquinoline
      clubbed 1,3,5-triazine derivatives.
AB  - AIMS:   Present report describes the in vitro antimalarial activity and docking
      analysis of seven 4-aminoquinoline-clubbed 1,3,5-triazine derivatives on pf-DHFR
      TS. METHODS AND RESULTS: The antimalarial activity was evaluated in vitro against
      chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Compounds were docked
      onto the active site of pf-DHFR-TS using docking server to explicate necessary
      structural requirements for antimalarial activity. CONCLUSION: Title molecules
      demonstrated considerable bioactivity against the malaria parasite. Docking
      analysis revealed deep engulfment of the molecules into the inner groove of pf
      DHFR-TS active site by making stable ligand-receptor posses. Hydrophobic
      interaction was identified as the only major interacting force playing a role
      between ligand-receptor interaction and minor with hydrogen bonds. SIGNIfiCANCE
      AND IMPACT OF THE STUDY: The study provided the novel insight into the necessary
      structural requirement for rationale-based antimalarial drug discovery.

PMID- 22394199
TI  - Two new oleanane-type saponins from the husks of Xanthoceras sorbifolia Bunge.
AB  - Two new oleanane-type pentacyclic triterpenoid saponins were isolated from the
      husks of Xanthoceras sorbifolia Bunge and their structures were elucidated as 3-O
      beta-D-glucopyranosyl (1 -> 6)-beta-D-glucopyranosyl-28-O-alpha-L-rhamnopyranosyl
      (1 -> 2) [beta-D-glucopyranosyl (1 -> 6)] beta-D-glucopyranosyl-21beta,22alpha
      dihydroxyl-olean-12,15-diene and 3-O-beta-D-glucopyranosyl (1 -> 2)-beta-D
      glucopyranosyl-28-O-alpha-L-rhamnopyranosyl (1 -> 2) [beta-D-glucopyranosyl (1 ->
      6)] beta-D-glucopyranosy-21beta,22alpha-dihydroxyl-olean-12-ene. Meanwhile, the
      cytotoxic activities of these two compounds were tested on human gastric cancer
      cell (SGC-7901) and hepatoma carcinoma cell (HepG-2).

PMID- 22394200
TI  - JNK- and Akt-mediated Puma expression in the apoptosis of cisplatin-resistant
      ovarian cancer cells.
AB  - BH3 (Bcl-2 homology domain 3)-only proteins have an important role in the
      cisplatin resistance of cells. However, the effect of BH3-only proteins on
      cisplatin-resistant ovarian cancer cells has not been thoroughly elucidated. Our
      results from the present study indicate that Puma plays a critical role in the
      apoptosis of chemo-resistant ovarian cancer cells treated with BetA (betulinic
      acid). The reduction of Puma expression inhibits Bax activation and apoptosis.
      However, p53 gene silencing has little effect on Puma activation. Further
      experiments demonstrated that Akt-mediated FoxO3a (forkhead box O3a) nuclear
      translocation and the JNK (c-Jun N-terminal kinase)/c-Jun pathway only partially
      trigger Puma induction and apoptosis, whereas dominant-negative c-Jun expression
      with FoxO3a reduction completely inhibits Puma expression and cell death.
      Furthermore, our results suggest that JNK regulates the Akt/FoxO3a signalling
      pathway. Therefore the dual effect of JNK can efficiently trigger Puma activation
      and apoptosis in chemoresistant cells. Taken together, our results demonstrate
      the role of Puma in BetA-induced apoptosis and the molecular mechanisms of Puma
      expression regulated by BetA during ovarian cancer cell apoptosis. Our findings
      suggest that the JNK-potentiated Akt/FoxO3a and JNK-mediated c-Jun pathways co
      operatively trigger Puma expression, which determines the threshold for
      overcoming chemoresistance in ovarian cancer cells.

PMID- 22394201
TI  - Esophageal replacement by colon interposition with microvascular surgery for
      patients with thoracic esophageal cancer: the utility of superdrainage.
AB  - Replacing the thoracic esophagus with the colon is one mode of reconstruction
      after esophagectomy for esophageal cancer. There is, however, a high incidence of
      postoperative necrosis of the transposed colon. This study evaluated the outcomes
      of colon interposition with the routine use of superdrainage by microvascular
      surgery. Twenty-one patients underwent colon interposition from 2004 to 2009. The
      strategy for colon interposition was to: (i) use the right hemicolon; (ii)
      reconstruct via the subcutaneous route; (iii) perform a microvascular venous
      anastomosis for all patients; and (iv) perform a microvascular arterial
      anastomosis when the arterial blood flow was insufficient. The clinicopathologic
      features, surgical findings, and outcomes were investigated. The colon was used
      because of a previous gastrectomy in 18 patients (85.7%) and synchronous gastric
      cancer in three patients (14.3%). Eight patients (38.1%) underwent preoperative
      chemoradiotherapy including three (14.3%) treated with definitive
      chemoradiotherapy. Seven patients (33.3%) underwent microvascular arterial
      anastomosis to supplement the right colon blood supply. Pneumonia occurred in
      four patients (19.0%). Anastomotic leakage was observed in five patients (23.8%);
      however, no colon necrosis was observed. The 3-year and 5-year overall survival
      rates were both 50.6%. Colon interposition with superdrainage results in
      successful treatment outcomes. This technique is one option for colon
      interposition employing the right hemicolon.

PMID- 22394202
TI  - Health-related lifestyle, physical and mental health in children of alcoholic
      parents.
AB  - AIM: To identify potential differences between children of alcoholics (COAs) and
      controls in their health-related lifestyle, mental and physical health. METHODS:
      The recruitment of COAs took place in inpatient and outpatient treatment and
      rehabilitation units. Controls were recruited in elementary and high schools. 57
      COAs (72% response rate) and 84 controls (88% response rate) aged between 12 and
      18 years completed a postal questionnaire about their health-related lifestyle,
      and mental and physical health. RESULTS: Bivariate analysis showed that COAs'
      families have higher unemployment rates and lower economic status (P = 0.000).
      COAs reported poorer school performance (P = 0.000), spending more time in
      sedentary (television: P = 0.000, Internet: P = 0.014, music: P = 0.040) and less
      time in physical activities (P = 0.048), having poorer eating habits (fruits and
      vegetables: P = 0.001, sweets: P = 0.001, fast food: P = 0.000, soft drinks: P =
      0.004), a higher substance use (cigarettes: P = 0.030; marijuana: P = 0.564,
      heavy drinking: P = 0.050) and more mental health difficulties (emotional
      symptoms: P = 0.015, conduct problems: P = 0.012, suicidal tendencies: P = 0.007,
      mental disorder: P = 0.040). Among COAs, girls reported more emotional and
      somatic symptoms compared to boys (P = 0.020 and P = 0.047, respectively).
      Multivariate analysis showed that after controlling for socioeconomic status,
      significant mental health and health-related lifestyle inequalities between COAs
      and controls persist. CONCLUSION: Our findings suggest that COAs have a less
      healthy lifestyle and more mental health difficulties above and beyond the poorer
      economic environment they live in.

PMID- 22394203
TI  - Sorafenib  in melanoma.
AB  - INTRODUCTION: Sorafenib is an orally available multi-kinase inhibitor that
      inhibits tumor proliferation by targeting multiple kinases including the vascular
      endothelial growth factor receptors VEGFR1, VEGFR2, VEGFR3 and the platelet
      derived growth factor receptor PDGFR, and it targets tumor progression by
      inhibiting FLT3, C-Kit and BRAF. Since BRAF mutations are frequent in melanoma,
      sorafenib was investigated in various Phase I, II and III clinical trials. The
      drug is well tolerated with mild to moderate adverse effects, which are mostly
      limited to cutaneous toxicity, diarrhea and fatigue. AREAS COVERED: Systematic
      literature review of the randomized trials using PubMed was performed. Original
      articles were reviewed and citations from those were also considered.
      Additionally, clinical trial databases were examined to identify and summarize
      ongoing trials of sorafenib in melanoma patients. EXPERT OPINION: Sorafenib as a
      monotherapy or in combination with chemotherapy is of limited use. Combining it
      with dacarbazine doubled the response rate and the progression-free survival in
      metastatic melanoma patients. Unfortunately, these results have never been
      evaluated in large randomized Phase III clinical trials. According to the trials
      conducted so far a subpopulation of patients experience substantial benefit,
      therefore it is essential to identify biomarkers to select the subgroups of
      patients that are more likely to respond to sorafenib. Furthermore, other less
      frequent subtypes such as mucosal or ocular melanoma still constitute promising
      targets; academic institutions are currently launching investigator-initiated
      trials in these indications.

PMID- 22394204
TI  - Nitric oxide production mediates oligogalacturonide-triggered immunity and
      resistance to Botrytis cinerea in Arabidopsis thaliana.
AB  - Nitric oxide (NO) regulates a wide range of plant processes from development to
      environmental adaptation. In this study, we investigated the production and/or
      function of NO in Arabidopsis thaliana leaf discs and plants elicited by
      oligogalacturonides (OGs) and challenged with Botrytis cinerea. We provided
      evidence that OGs triggered a fast and long lasting NO production which was
      Ca(2+) dependent and involved nitrate reductase (NR). Accordingly, OGs triggered
      an increase of both NR activity and transcript accumulation. NO production was
      also sensitive to the mammalian NO synthase inhibitor L-NAME. Intriguingly, we
      showed that L-NAME affected NO production by interfering with NR activity, thus
      questioning the mechanisms of how this compound impairs NO synthesis in plants.
      We further demonstrated that NO modulates RBOHD-mediated reactive oxygen species
      (ROS) production and participates in the regulation of OG-responsive genes such
      as anionic peroxidase (PER4) and a beta-1,3-glucanase. Mutant plants impaired in
      PER4 and beta-1,3-glucanase, as well as Col-0 plants treated with the NO
      scavenger cPTIO, were more susceptible to B. cinerea. Taken together, our
      investigation deciphers part of the mechanisms linking NO production, NO-induced
      effects and basal resistance to B. cinerea.

PMID- 22394205
TI  - The diagnostic value of immunohistochemically detected methylthioadenosine
      phosphorylase deficiency in malignant pleural mesotheliomas.
AB  - AIMS:   Malignant pleural mesothelioma (MPM) often causes diagnostic difficulties
      for pathologists. We assessed whether loss of methylthioadenosine phosphorylase
      (MTAP), a key enzyme in the intracellular recycling of adenosine triphosphate
      (ATP) often deleted in MPM, could be detected with immunohistochemistry (IHC) and
      used as a diagnostic marker for MPM. METHODS AND RESULTS:   We used IHC to detect
      MTAP in a cohort of 99 MPMs and 39 reactive mesothelial proliferations (RP)
      (reactive mesothelial hyperplasia n = 33, reactive pleural fibrosis n = 6). MTAP
      staining was assessed by an H score. The median H score of the RP cohort was set
      as a reference point. Cases with H scores below this reference point were
      considered to have decreased MTAP expression. We found that 64 of 99 (65%) of the
      investigated MPMs had decreased MTAP expression, while this was only true for
      nine of 39 (23%) of the RPs (P = 0.001). We further evaluated MTAP expression in
      a cohort of coagulated pleural effusions from 14 patients with MPM and 20
      patients with RP by using a double-staining technique with Wilms tumour 1 (WT1)
      as a mesothelial marker. In these samples, decreased MTAP expression diagnosed
      MPM with a sensitivity of 71% and a specificity of 90%. CONCLUSIONS:   Decreased
      MTAP expression could potentially be useful in combination with other markers in
      the diagnosis of MPM.

PMID- 22394207
TI  - Development and application of an enzyme-linked immunosorbent assay for specific
      detection of mangiferin content in various cultivars of Mangifera indica leaves
      using anti-mangiferin polyclonal antibody.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed for determining
      mangiferin content in plant samples using a polyclonal antibody (PAb) against
      mangiferin. The developed ELISA showed a full measurement range from 0.12 to
      31.25 MUg/mL mangiferin with a relative standard deviation (RSD) less than 6% for
      both intra- and interassay precision levels. The accuracy was determined by a
      percent recovery experiment at three concentration levels and it showed 97.8%
      103.7% recovery in Mangifera indica leaf samples. The developed ELISA exhibited a
      high correlation value (R2 = 0.992) with the standard high-performance liquid
      chromatography (HPLC) method in various mangiferin-containing plant samples. Our
      results suggest that the validated ELISA methodology using a PAb against
      mangiferin can be applied to determine mangiferin content with high specificity,
      rapidity and simplicity in various mangiferin-containing plant samples. The
      mangiferin content in the mature leaves of fifty M. indica cultivars were
      determined using the developed ELISA. The mangiferin contents ranged from 1.94 +/
      0.13% to 13.79 +/- 0.84% dry wt. The Thawai cultivar leaves contained the
      highest level of mangiferin (13.79 +/- 0.84% dry wt), but it is a rare cultivar.
      The Namdokmai, which is more commonly cultivated in Thailand, contain 12.41 +/-
      0.60% dry wt mangiferin; therefore, this cultivar leaf was recommended as the
      source of raw material for the pharmaceutical, nutraceutical and cosmetic product
      industries. PRACTICAL APPLICATION: Currently, natural heath products are accepted
      worldwide for healthcare. Mangiferin-containing plants and products exhibit
      health benefits against oxidative stress-related diseases, such as cardiovascular
      diseases, cancer, dyslipidemia and diabetes. We have developed an ELISA with high
      specificity, rapidity and simplicity for the quality control of mangiferin
      derived product production. Moreover, we found that the Namdokmai leaf, a Thai M.
      indica cultivar, was recommended as the source of raw material for the
      pharmaceutical, nutraceutical and cosmetic product industry because of its high
      mangiferin content and natural prevalence.

PMID- 22394209
TI  - Editorial.

PMID- 22394206
TI  - Construct validity of the item-specific deficit approach to the California verbal
      learning test (2nd Ed) in HIV infection.
AB  - Impairment in list learning and recall is prevalent in HIV-infected individuals
      and is strongly predictive of everyday functioning outcomes. Consistent with its
      predominant frontostriatal pathology, the memory profile associated with HIV
      infection is best characterized as a mixed encoding/retrieval profile. The Item
      Specific Deficit Approach (ISDA) was developed by Wright et al. (2009) to elicit
      indices of Encoding, Consolidation, and Retrieval from the well-validated
      California Verbal Learning Test (CVLT; Delis, Kramer, Kaplan, & Ober, 1987,
      2000). The current study evaluated construct validity of the ISDA for the CVLT-II
      in 40 persons with HIV-associated neurocognitive disorders (HIV+/HAND+), 103 HIV
      infected persons without HAND (HIV+/HAND-), and 43 seronegative comparison
      participants (HIV-). Results provided mixed support for the construct validity of
      ISDA indices. HIV+/HAND+ individuals performed significantly more poorly than
      persons in the HIV+/HAND- and HIV- groups on ISDA Encoding, Consolidation, and
      Retrieval deficit indices, which demonstrated adequate classification accuracy
      for diagnosing HIV+/HAND+ participants and evidence of both convergent (e.g.,
      episodic memory) and divergent (e.g., motor skills) correlations in the
      HIV+/HAND+ participants. However, highly intercorrelated ISDA indices and
      traditional CVLT-II measures showed comparable between-groups effect sizes,
      classification accuracy, and correlations to other memory tests, thereby raising
      uncertainties about the incremental value of the ISDA approach in clinical
      neuroAIDS research.

PMID- 22394208
TI  - Exposure assessment to ochratoxin A in Catalonia (Spain) based on the consumption
      of cereals, nuts, coffee, wine, and beer.
AB  - Ochratoxin A (OTA) was analysed in composite samples of cereal-based baby foods,
      beer, breakfast cereals (corn- and rice and wheat-based), loaf bread, peanuts and
      pistachios. Foodstuffs were collected in hypermarkets and supermarkets from 12
      cities in the Spanish region of Catalonia, and composite samples were prepared
      for analysis involving liquid-liquid extraction, followed by immunoaffinity
      column clean-up and HPLC with fluorescence detection. Consumption data for the
      selected foodstuffs were collected by means of a food-frequency questionnaire.
      The studied population was grouped by age in infants, children, adolescents and
      adults; and exposure to OTA through the specified foodstuffs, and through wine
      and coffee, was assessed. Exposure assessment was done through deterministic and
      probabilistic modelling of the contamination and consumption data. OTA occurrence
      and mean of positive samples (ng g(-1) or ng ml(-1), for beer) were the
      following: 8.7% and 0.233 in baby foods; 88.7% and 0.022 in beer; 2.8% and 0.728
      in corn-based breakfast cereals; 25% and 0.293 in wheat-based breakfast cereals;
      12.9% and 0.283 in loaf bread; 41.7% and 0.241 in peanuts; and 2.9% and 0.228 in
      pistachios. The median estimated daily intake of OTA through the foodstuffs by
      each age group were below the latest provisional tolerable daily intakes (PTDIs)
      of 17 and 14 ng kg(-1) bw day(-1) recommended by the European Food Safety
      Authority (EFSA) in 2006 and the Joint FAO/WHO Expert Committee on Food Additives
      (JECFA) in 2007, respectively, ranging from 1% and 2% of those values in
      adolescents and children, to 3% and 11% in adults and infants.

PMID- 22394210
TI  - Prevalence, phenotypic traits and molecular characterization of emetic toxin
      producing Bacillus cereus strains isolated from human stools in Korea.
AB  - AIMS: To investigate the prevalence and genotypic/phenotypic characters of emetic
      toxin-producing Bacillus cereus strains isolated from sporadic food poisoning
      cases in Korea. METHODS AND RESULTS: The prevalence of emetic B. cereus was
      determined in 56 899 stool samples from sporadic food poisoning cases in Korea
      between 2004 and 2006. We assessed toxin profiles, phenotypic traits and
      antibiotic resistance. The molecular subtyping was ascertained using an automated
      repetitive sequence-based PCR (rep-PCR) system, DiversiLabTM, with these emetic
      strains isolated from sporadic food poisoning cases and other emetic strains
      isolated from an outbreak and food samples. Emetic B. cereus was present in
      0.012% of sporadic food poisoning cases. The prevalence of nheABC, hblCDA, cytK
      and entFM enterotoxin genes among emetic strains was 100, 14.3, 14.3 and 100%,
      respectively. Most emetic strains were negative for salicin hydrolysis (100%),
      starch fermentation (85.7%) and haemolysis (85.7%). One emetic isolate, VK7,
      exhibited several unique traits, such as harbouring the hbl gene and ability to
      hydrolyse starch. All isolated strains were highly resistant to beta-lactam
      antibiotics. All emetic strains except VK7 exhibited an identical rep-PCR banding
      pattern, while nonemetic strains were classified into various pulsotypes.
      CONCLUSIONS: Most emetic strains except one isolate exhibited similar
      genotypic/phenotypic traits and subtyping pattern. Automatic rep-PCR
      (DiversiLabTM) may be used to discriminate emetic strains from nonemetic strains,
      although we could not distinguish between most emetic strains using that.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Result of this study may contribute an
      extended database on the prevalence and toxigenic traits of emetic B. cereus
      strains isolated from Korea.

PMID- 22394211
TI  - Particles trapped at the droplet interface in water-in-water emulsions.
AB  - Water-in-water emulsions were formed by mixing incompatible aqueous solutions of
      dextran and poly(ethylene oxide) (PEO) in the presence of latex or protein
      particles. It was found that particles with a radius as small as 0.1 MUm become
      trapped at the interface between the PEO- and dextran-rich phases with
      interfacial tensions down to 10(-6) N/m. The particles were visualized at the
      interface of the emulsion droplets using confocal laser scanning microscopy
      (CLSM) allowing determination of the contact angle. Various degrees of coverage
      with particles could be observed. On densely covered droplets, the particles had
      a hexagonal crystalline order. At intermediate coverage, transient clustering of
      the particles was observed. The diffusion coefficient of the particles at the
      interface was determined using multiparticle tracking. Fusion of droplets was
      observed in all cases leading eventually to macroscopic phase separation.

PMID- 22394213
TI  - Synthesis of metal oxide nanostructures by direct sol-gel chemistry in
      supercritical fluids.

PMID- 22394212
TI  - Site-specific traceless coupling of potent cytotoxic drugs to recombinant
      antibodies for pharmacodelivery.
AB  - Aldehyde drugs are gaining increasing research interest, considering that
      aldehyde dehydrogenases overexpression is characteristic of cancer stem cells.
      Here, we describe the traceless site-specific coupling of a novel potent drug,
      containing an aldehyde moiety, to recombinant antibodies, which were engineered
      to display a cysteine residue at their N-terminus, or a 1,2-aminothiol at their C
      terminus. The resulting chemically defined antibody-drug conjugates represent the
      first example in which a thiazolidine linkage is used for the targeted delivery
      and release of cytotoxic agents.

PMID- 22394214
TI  - "What--me worry?" "Why so serious?": a personal view on the Fukushima nuclear
      reactor accidents.
AB  - Infrequently, it seems that a significant accident precursor or, worse, an actual
      accident, involving a commercial nuclear power reactor occurs to remind us of the
      need to reexamine the safety of this important electrical power technology from a
      risk perspective. Twenty-five years since the major core damage accident at
      Chernobyl in the Ukraine, the Fukushima reactor complex in Japan experienced
      multiple core damages as a result of an earthquake-induced tsunami beyond either
      the earthquake or tsunami design basis for the site. Although the tsunami itself
      killed tens of thousands of people and left the area devastated and virtually
      uninhabitable, much concern still arose from the potential radioactive releases
      from the damaged reactors, even though there was little population left in the
      area to be affected. As a lifelong probabilistic safety analyst in nuclear
      engineering, even I must admit to a recurrence of the doubt regarding nuclear
      power safety after Fukushima that I had experienced after Three Mile Island and
      Chernobyl. This article is my attempt to "recover" my personal perspective on
      acceptable risk by examining both the domestic and worldwide history of
      commercial nuclear power plant accidents and attempting to quantify the risk in
      terms of the frequency of core damage that one might glean from a review of
      operational history.

PMID- 22394215
TI  - Bicalutamide nanocrystals with improved oral bioavailability: in vitro and in
      vivo evaluation.
AB  - CONTEXT: Bicalutamide (BCT) is an antiandrogenic compound belonging to
      Biopharmaceutics Classification System (BCS) class II drug. Thus it has limited
      aqueous solubility and hence limited oral bioavailability. OBJECTIVE: The purpose
      of the present investigation was to obtain stable nanocrystals of BCT with
      improved kinetic solubility, dissolution and pharmacokinetic profiling. MATERIALS
      AND METHODS: BCT nanocrystals were prepared by antisolvent precipitation method
      using Soluplus, a novel amphiphilic polymer. Nanocrystals were characterized for
      particle size, powder X-ray diffraction analysis (PXRD), in vitro dissolution, in
      vivo pharmacokinetic profile and stability. RESULTS AND DISCUSSION: The obtained
      nanocrystals had particle size of 168 nm and were spherical in shape. The
      nanocrystals exhibited fivefold increase in kinetic solubility as compared to
      pure drug and 85% dissolution in 60 min. PXRD studies established the retention
      of crystalline polymorphic form II. The in vivo pharmacokinetic study
      demonstrated that the Cmax and AUC of nanosized BCT were about 3.5 times higher
      as compared to pure drug. CONCLUSION: Nanosizing of BCT significantly improved
      the pharmacokinetic profile of the drug administered to rats. Prepared
      nanocrystals were found to be stable over the entire stability period. Thus the
      use of amphiphilic polymer like Soluplus singularly helped in efficient size
      reduction and stabilization of the drug.

PMID- 22394216
TI  - Substituent effects on CL...N, S...N, and P...N noncovalent bonds.
AB  - Cl, S, and P atoms have previously been shown as capable of engaging in a
      noncovalent bond with the N atom on another molecule. The effects of substituents
      B on the former atoms on the strength of this bond are examined, and it is found
      that the binding energy climbs in the order B = CH(3) < NH(2) < CF(3) < OH < Cl <
      NO(2) < F. However, there is some variability in this pattern, particularly for
      the NO(2) group. The A...N bonds (A = Cl, S, P) can be quite strong, amounting to
      as much as 10 kcal/mol. The binding energy arises from approximately equal
      contributions from its induction and electrostatic components, although the
      former becomes more dominant for the stronger bonds. The induction energy is due
      in large measure to the transfer of charge from the N lone pair to a B-A sigma*
      antibonding orbital of the electron-acceptor molecule containing Cl, S, or P.
      These A...N bonds typically represent the lowest-energy structure on each
      potential energy surface, stronger than H-bonds such as NH...F, CH...N, or
      SH...N.

PMID- 22394217
TI  - Bacterial flora of the human oral cavity, and the upper and lower esophagus.
AB  - This reference study aims to survey the bacterial flora of the healthy lower
      human esophagus and to compare it with that of the upper esophagus and oral
      mucosa. The use of biopsies, in addition to brush samples, allows inclusion of
      not only transient bacteria present on the surface but also bacteria residing in
      the epithelia, and the yield of the two methods can be compared. Forty patients
      scheduled for surgery for reasons with no known influence on esophageal flora and
      with no symptoms or endoscopic signs of esophageal disease were included. Samples
      were collected from the oral, upper esophageal, and lower esophageal mucosa using
      sealed brushes and biopsy forceps. Colonies cultivated on agar plates were
      classified and semiquantified. Twenty-three different bacterial species were
      identified, with similar strains present at the three sites. The most common
      group of bacteria was viridans streptococci, with an occurrence rate in brush
      samples and biopsies of 98% and 95%, respectively. The median number of species
      occurring in the oral cavity, upper esophagus, and lower esophagus was between 3
      and 4 (range 0-7). The total number of species in the oral cavity was
      significantly higher when compared with either level in the esophagus, while the
      yields obtained by brush and biopsy sampling were highly correlated. Hence, the
      normal human esophagus is colonized with a resident bacterial flora of its own,
      which has similarities to that of the oral mucosa. There are diverse species that
      make up this flora, although in relatively low amounts. The most frequent
      inhabitants of the esophagus are streptococci, with an occurrence rate in brush
      samples and biopsies of 95-98%. Comparative studies of patients with eosinophilic
      esophagitis and gastroesophageal reflux disease are warranted.

PMID- 22394218
TI  - Copper-free asymmetric allylic alkylation using grignard reagents on bifunctional
      allylic bromides.
AB  - A series of substrates containing a vinylic bromide were employed in a copper
      free methodology using bidendate NHC ligands. The desired compounds are generally
      obtained with good enantioselectivity and good regioselectivity. Importantly the
      copper-catalyzed system afforded a lower enantioselectivity value. The catalytic
      products could be transformed into a broad scope of new 1,1-disubstituted olefins
      in a single step transformation without erosion of the enantioselectivity.

PMID- 22394219
TI  - Ubiquitination-mediated regulation of interferon responses.
AB  - Interferon cytokine family members shape the immune response to protect the host
      from both pathologic infections and tumorigenesis. To mediate their physiologic
      function, interferons evoke a robust and complex signal transduction pathway that
      leads to the induction of interferon-stimulated genes with both proinflammatory
      and antiviral functions. Numerous mechanisms exist to tightly regulate the extent
      and duration of these cellular responses. Among such mechanisms, the post
      translational conjugation of ubiquitin polypeptides to protein mediators of
      interferon signaling has emerged as a crucially important mode of control. In
      this mini-review, we highlight recent advances in our understanding of these
      ubiquitin-mediated mechanisms, their exploitation by invading viruses, and their
      possible utilization for medical intervention.

PMID- 22394221
TI  - Construction of histidine-tagged yeast mitochondrial cytochrome c oxidase for
      facile purification of mutant forms.
AB  - Yeast CcO (cytochrome c oxidase) has been developed as a facile system for the
      production and analysis of mutants of a mitochondrial form of CcO for mechanistic
      studies. First, a 6H tag (His6 tag) was fused to the C-terminus of a nuclear
      encoded subunit of CcO from yeast Saccharomyces cerevisiae. This allowed
      efficient purification of a WT (wild-type) mitochondrial CcO, 6H-WT (yeast CcO
      with a 6H tag on the nuclear-encoded Cox13 subunit), with a recovery yield of
      45%. Its catalytic-centre activity [~180 e.s(-1) (electrons per s)], UV-visible
      signatures of oxidized and reduced states and ability to form the P(M) ['peroxy'
      (but actually a ferryl/radical state)] and F (ferryl) intermediates confirm
      normal functioning of the histidine-tagged protein. Point mutations were
      introduced into subunit I of the 6H-WT strain. All mutants were screened for
      their ability to assemble CcO and grow on respiratory substrate. One such mutant
      [6H-E243DI (the 6H-WT strain with an additional mutation of E243D in
      mitochondrial DNA-encoded subunit I)] was purified and showed ~50% of the 6H-WT
      catalytic-centre activity, consistent with the effects of the equivalent mutation
      in bacterial oxidases. Mutations in both the D and the H channels affect
      respiratory growth and these effects are discussed in terms of their putative
      roles in CcO mechanism.

PMID- 22394222
TI  - Withania somnifera chemotypes NMITLI 101R, NMITLI 118R, NMITLI 128R and
      withaferin A protect Mastomys coucha from Brugia malayi infection.
AB  - Withania somnifera is an ayurvedic Indian medicinal plant whose immunomodulatory
      activities have been widely used as a home remedy for several ailments. We
      recently observed immunostimulatory properties in the root extracts of chemotypes
      NMITLI-101, NMITLI-118, NMITLI-128 and pure withanolide, withaferin A. In the
      present study, we evaluated the potential immunoprophylactic efficacies of these
      extracts against an infective pathogen. Our results show that administration of
      aqueous ethanol extracts (10 mg/kg) and withaferin A (0.3 mg/kg), 7 days before
      and after challenge with human filarial parasite Brugia malayi, offers
      differential protection in Mastomys coucha with chemotype 101R offering best
      protection (53.57%) as compared to other chemotypes. Our findings also
      demonstrate that establishment of B. malayi larvae was adversely affected by
      pretreatment with withaferin A as evidenced by 63.6% reduction in adult worm
      establishment. Moreover, a large percentage of the established female worms
      (66.2%) also showed defective embryogenesis. While the filaria-specific
      immunological response induced by withaferin A and NMITLI-101 showed a mixed
      Th1/Th2 phenotype, 118R stimulated production of IFN-gamma and 128R increased
      levels of IL-4. Taken together, our findings reveal potential immunoprophylactic
      properties of W. somnifera, and further studies are needed to ascertain the
      benefits of this plant against other pathogens as well.

PMID- 22394223
TI  - Antigenic fractions of Leishmania (Viannia) braziliensis: the immune response
      characterization of patients at the initial phase of disease.
AB  - American cutaneous leishmaniasis (ACL) has different clinical manifestations and
      these manifestations are dependent on the immunological status of the host. As
      CD4(+)  and CD8(+)  T cells and their mediators play a fundamental role in the
      host response to Leishmania and there is also a search for antigenic molecules to
      be used as future vaccines and tools for prognostic tests, this study
      characterized ACL patients' immune response after stimulation with soluble and
      insoluble fractions of L. (V.) braziliensis. We demonstrated a prevailing
      production of the Th2 cytokines, IL-4 and IL-10 and a specific production of IFN
      gamma and TNF-alpha in patients before treatment. There was also a predominance
      of CD4(+)  T cells and a small percentage CD8(+)  T cells. The insoluble
      antigenic fraction primarily stimulated CD4(+)  T cells, while the soluble
      antigenic fraction showed a mixed profile, with CD4(+)  T cells being the main
      responsible for Th2 cytokines and CD8(+)  T cells for Th1 cytokines. Therefore,
      our results showed that a down-modulation of the Th1 type of response occurs in
      the initial phase of L. braziliensis disease, being the antigenic fractions
      capable of stimulating a specific immune response.

PMID- 22394224
TI  - A drug evaluation of 1% tenofovir gel and  tenofovir disoproxil fumarate  tablets
      for the prevention of HIV infection.
AB  - INTRODUCTION: More than a million people acquire HIV infection annually. Pre
      exposure prophylaxis (PrEP) using antiretrovirals is currently being investigated
      for HIV prevention. Oral and topical formulations of tenofovir have undergone
      preclinical and clinical testing to assess acceptability, safety and
      effectiveness in preventing HIV infection. AREAS COVERED: The tenofovir drug
      development pathway from compound discovery, preclinical animal model testing and
      human testing were reviewed for safety, tolerability and efficacy. Tenofovir is
      well tolerated and safe when used both systemically or applied topically for HIV
      prevention. High drug concentrations at the site of HIV transmission and
      concomitant low systemic drug concentrations are achieved with vaginal
      application. Coitally applied gel may be the favored prevention option for women
      compared with the tablets, which may be more suitable for prevention in men and
      sero-discordant couples. However, recent contradictory effectiveness outcomes in
      women need to be better understood. EXPERT OPINION: Emerging evidence has brought
      new hope that antiretrovirals can potentially change the course of the HIV
      epidemic when used as early treatment for prevention, as topical or oral PrEP.
      Although some trial results appear conflicting, behavioral factors, adherence to
      dosing and pharmacokinetic properties of the different tenofovir formulations and
      dosing approaches offer plausible explanations for most of the variations in
      effectiveness observed in different trials.

PMID- 22394226
TI  - Smoking behaviours among young people in custody in New South Wales, Australia.
AB  - INTRODUCTION AND AIMS: Despite smoking prevalence reductions in the general
      community, rates remain high among socially disadvantaged populations. This study
      describes the prevalence and predictors for smoking among young people in
      custody. DESIGN AND METHODS: The 2009 NSW Young People in Custody Health Survey
      was conducted in nine juvenile detention centres. This paper reports on findings
      from the baseline questionnaire which included questions about smoking
      behaviours. Chi-squared statistics were used to compare the smoking
      characteristics by gender and Aboriginality. Logistic regression was used to
      determine predictors of smoking behaviours. RESULTS: The baseline questionnaire
      included 316 participants with a response rate of 83%. The sample was 88% male,
      48% Aboriginal, with an average age of 17 years (range 13-21 years). Nearly all
      (94%) participants had ever smoked tobacco, with 79% reporting smoking daily
      prior to custody. Predictors of heavy smoking (20 or more cigarettes per day)
      prior to custody included being female, high psychological distress and conduct
      disorder. Predictors for being a current smoker included being on remand, risky
      drinking and most or all friends as smokers. Predictors of being an aspirational
      smoker (will smoke on release) included using illicit drugs at least weekly prior
      to custody, and having most or all friends as smokers. DISCUSSION AND
      CONCLUSIONS: Rates of smoking in young people entering custody are exceptionally
      high. Many young people continue to smoke during their incarceration, with an
      increasing aspiration to smoke upon release. Effective programs are needed that
      address these smoking behaviours in young people in custody.

PMID- 22394225
TI  - Lung mast cell density defines a subpopulation of patients with idiopathic
      pulmonary fibrosis.
AB  - AIMS: The relationship of mast cells to the pathogenesis of lung fibrosis remains
      undefined despite recognition of their presence in the lungs of patients with
      pulmonary fibrosis. This study was performed to characterize the relationship of
      mast cells to fibrotic lung diseases. METHODS AND RESULTS: Lung tissues from
      patients with idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity
      pneumonitis (HP), systemic sclerosis (SSc)-related interstitial lung disease
      (ILD) and normal individuals were subjected to chymase immunostaining and the
      mast cell density quantified. Eosinophils were quantified by immunostaining for
      eosinophil peroxidase. Changes in lung function were correlated with mast cell
      density. Lung tissue obtained from IPF patients had a higher density of chymase
      immunoreactive mast cells than that from patients with HP, SSc-related ILD or
      normal lungs. IPF lung tissue had a higher density of eosinophils than normal
      lung. There was no correlation between mast cell density and eosinophil density
      in IPF lung. IPF patients with high mast cell density had a slower rate of
      decline in forced vital capacity (FVC) than IPF patients with low mast cell
      density. CONCLUSIONS: Mast cell density in IPF lungs is higher than in other
      fibrotic lung diseases and normal lungs. Increased mast cell density in IPF may
      predict slower disease progression.

PMID- 22394227
TI  - Antagonistic effect of the Ainu-selected traditional beneficial plants on the
      transformation of an aryl hydrocarbon receptor.
AB  - Transformation of an aryl hydrocarbon receptor (AhR) is the initial step to
      express the multiple toxicity of halogenated and polycyclic aromatic hydrocarbons
      (HAHs and PAHs) including dioxins. Therefore, it has been suggested that
      suppression of the transformation induced by HAHs and PAHs leads to reduce their
      toxicological effects. In this study, the antagonistic effect of 110 indigenous
      plants (192 plant parts) used as medicine and/or food by the Ainu on the 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-induced AhR transformation was investigated.
      Of these, a stalk of Aralia elata (Miq.) Seemann and a bark of Fraxinus
      mandshurica Rupr. var. japonica Maxim. exhibited the strong antagonistic effect
      in a dose-dependent manner. An antioxidative activity and polyphenol content were
      also measured, and the strong correlation (r= 0.96) between these two parameters
      could be confirmed. However, correlation coefficients of the antagonistic effect
      of 192 extracts compared to their antioxidative activity and polyphenol content
      were 0.17 and 0.20, respectively. These results suggest that the Ainu-selected
      traditional beneficial plants are useful source for findings of novel AhR
      antagonists, and the antagonistic activity of these plants may be independent on
      their antioxidative activity and polyphenol content. PRACTICAL APPLICATION: Our
      findings lead to discovery of the valuable plants used by the Ainu and the novel
      active compounds useful for human's life, and furthermore, may contribute to the
      development of new medicines and functional foods.

PMID- 22394229
TI  - Determination of aflatoxins in by-products of industrial processing of cocoa
      beans.
AB  - This study has examined the occurrence of aflatoxins in 168 samples of different
      fractions obtained during the processing of cocoa in manufacturing plants (shell,
      nibs, mass, butter, cake and powder) using an optimised methodology for cocoa by
      products. The method validation was based on selectivity, linearity, limit of
      detection and recovery. The method was shown to be adequate for use in
      quantifying the contamination of cocoa by aflatoxins B(1), B(2), G(1) and G(2).
      Furthermore, the method was easier to use than other methods available in the
      literature. For aflatoxin extraction from cocoa samples, a methanol-water
      solution was used, and then immunoaffinity columns were employed for clean-up
      before the determination by high-performance liquid chromatography. A survey
      demonstrated a widespread occurrence of aflatoxins in cocoa by-products, although
      in general the levels of aflatoxins present in the fractions from industrial
      processing of cocoa were low. A maximum aflatoxin contamination of 13.3 ng g(-1)
      was found in a nib sample. The lowest contamination levels were found in cocoa
      butter. Continued monitoring of aflatoxins in cocoa by-products is nevertheless
      necessary because these toxins have a high toxicity to humans and cocoa is widely
      consumed by children through cocoa-containing products, like candies.

PMID- 22394230
TI  - L1 insertion within SPEF2 gene is associated with increased litter size in the
      Finnish Yorkshire population.
AB  - Immotile, short-tail sperm defect (ISTS) expanded in the Finnish Yorkshire
      population in the end of 1990s. The causal mutation for this defect is a recent
      L1 insertion within the SPEF2 gene in chromosome 16. Even though all homozygous
      boars are eliminated from the population because of infertility, the amount of
      affected boars increased rapidly until marker-assisted selection against the
      defect was established. To elucidate the associated effects of the ISTS defect on
      production traits, we have investigated the association of the L1 insertion and
      PRLR haplotype with reproduction traits in the Finnish Yorkshire population. Two
      data sets including 357 sows and 491 AI-boars were genotyped for the presence of
      the L1 insertion and analysed for association with reproduction traits. A Proc
      Mixed procedure (SAS Inc) and a software package for analysing multivariate mixed
      models (DMU) were used to study the effect of polymorphisms on reproduction
      traits. The L1-insertion within SPEF2 gene was associated with litter size in the
      first parity. The SPEF2 gene is located adjacent to a candidate gene for litter
      size in the pig, PRLR. Haplotypes within PRLR exon 10 were analysed in data set
      of 93 AI-boars for the association with reproduction traits. However, no
      associations were detected within the analysed data set indicating that PRLR
      sequence variants are not the causal cause for the identified effect on litter
      size.

PMID- 22394228
TI  - Computerized neuropsychological assessment devices: joint position paper of the
      American Academy of Clinical Neuropsychology and the National Academy of
      Neuropsychology.
AB  - This joint position paper of the American Academy of Clinical Neuropsychology and
      the National Academy of Neuropsychology sets forth our position on appropriate
      standards and conventions for computerized neuropsychological assessment devices
      (CNADs). In this paper, we first define CNADs and distinguish them from examiner
      administered neuropsychological instruments. We then set forth position
      statements on eight key issues relevant to the development and use of CNADs in
      the healthcare setting. These statements address (a) device marketing and
      performance claims made by developers of CNADs; (b) issues involved in
      appropriate end-users for administration and interpretation of CNADs; (c)
      technical (hardware/software/firmware) issues; (d) privacy, data security,
      identity verification, and testing environment; (e) psychometric development
      issues, especially reliability and validity; (f) cultural, experiential, and
      disability factors affecting examinee interaction with CNADs; (g) use of
      computerized testing and reporting services; and (h) the need for checks on
      response validity and effort in the CNAD environment. This paper is intended to
      provide guidance for test developers and users of CNADs that will promote
      accurate and appropriate use of computerized tests in a way that maximizes
      clinical utility and minimizes risks of misuse. The positions taken in this paper
      are put forth with an eye toward balancing the need to make validated CNADs
      accessible to otherwise underserved patients with the need to ensure that such
      tests are developed and utilized competently, appropriately, and with due concern
      for patient welfare and quality of care.

PMID- 22394231
TI  - Estimation of variance components for postpartum dysgalactia syndrome in sows.
AB  - The postpartum dysgalactia syndrome (PDS) represents one of the most important
      diseases after parturition in sows. The genetic background of the disease has
      been investigated some time ago and heritability estimates around 0.10 have been
      obtained. To compute current estimates, a dataset of 1680 sampled sows and their
      2001 clinically examined litters was used for variance components estimation with
      a threshold liability model. Affected sows were defined through clinical
      examination 12-48 h after parturition. Posterior mean of additive genetic
      variance was 0.10 and estimated heritability for PDS averaged 0.0879 with a 95%
      confidence interval of 0.0876 and 0.0881. The results are in agreement with those
      of other studies and emphasize the importance of considering the genetic
      predisposition for susceptibility to PDS as well as of additional factors
      including hygiene and management conditions.

PMID- 22394232
TI  - Genetic correlations between males, females and castrates for residual feed
      intake, feed conversion ratio, growth rate and carcass composition traits in
      Large White growing pigs.
AB  - Data were collected in the course of a divergent selection experiment for
      residual feed intake (RFI) of Large White growing pigs. This data set was used to
      estimate (i) heritability for RFI and genetic correlations of RFI with growth and
      carcass traits within the three sexes (male, castrate and female) and (ii)
      genetic correlations between sexes for these traits. Individual feed intake of
      animals raised in collective pens was measured by single-place electronic feeders
      on 1121 males (candidates for selection), 508 females and 535 castrates (sibs of
      candidates). Variance components were estimated using the REML methodology
      applied to a multitrait animal model. Estimates of heritability for RFI were 0.16
      +/- 0.04, 0.16 +/- 0.08 and 0.23 +/- 0.10 for males, females and castrates,
      respectively. Estimates of genetic correlations between sexes for homologous
      traits were not significantly different from 1 (0.88 to 0.99 for RFI, 0.79 to
      0.99 for growth traits and 0.65 to 0.99 for carcass composition traits). The
      relatively low genetic correlations between castrates and males or females for
      backfat thickness (0.65 and 0.69, respectively) suggest the presence of genotype
      by sex interactions for this trait.

PMID- 22394233
TI  - Whole-genome QTL scan for ultrasound and carcass merit traits in beef cattle
      using Bayesian shrinkage method.
AB  - Fine mapping of quantitative trait loci (QTL) for 16 ultrasound measurements and
      carcass merit traits that were collected from 418 hybrid steers was conducted
      using 1207 SNP markers covering the entire genome. These SNP markers were
      evaluated using a Bayesian shrinkage estimation method and the empirical critical
      significant thresholds (alpha = 0.05 and alpha = 0.01) were determined by
      permutation based on 3500 permuted datasets for each trait to control the genome
      wide type I error rates. The analyses identified a total of 105 QTLs (p < 0.05)
      for seven ultrasound measure traits including ultrasound backfat, ultrasound
      marbling and ultrasound ribeye area and 113 QTLs for seven carcass merit traits
      of carcass weight, grade fat, average backfat, ribeye area, lean meat yield,
      marbling and yield grade. Proportion of phenotypic variance accounted for by a
      single QTL ranged from 0.06% for mean ultrasound backfat to 4.83% for carcass
      marbling (CMAR) score, while proportion of the phenotypic variance accounted for
      by all significant (p < 0.05) QTL identified for a single trait ranged from 4.54%
      for carcass weight to 23.87% for CMAR.

PMID- 22394234
TI  - Predictive ability of alternative models for genetic analysis of clinical
      mastitis.
AB  - Mastitis in cows can be defined as a binary trait, reflecting presence or absence
      of clinical mastitis (CM), or as a count variable, number of mastitis cases
      (NCM), within a defined time interval. Many different models have been proposed
      for genetic analyses of mastitis, and the objective of this study was to evaluate
      the predictive ability and sire predictions of a set of models for genetic
      evaluation of CM or NCM. Linear- and threshold liability models for CM, and
      linear, censored ordinal threshold, and zero-inflated Poisson (ZIP) models for
      NCM were compared in a cross-validation study. To assess the ability of these
      models to predict future data, records from 620492 first-lactation Norwegian Red
      cows, which were daughters of 3064 sires, were evaluated in a fourfold cross
      validation scheme. The mean squared error of prediction was used for model
      comparison. All models but ordinal threshold model equally performed when
      comparing the overall predictive ability. This result was on average, across sick
      and healthy cows; however, the models behaved differently for each category of
      animals. For example, healthy cows were predicted better by the threshold and
      linear models for binary data and ZIP model, whereas for mastitic cows, the
      ordinal threshold model was by far the best model. Predicted sire effects and
      rankings of sires were highly correlated across all models. For practical
      purposes, the linear models are very competitive with the nonlinear models.

PMID- 22394235
TI  - Genetic analyses of pathogen-specific mastitis.
AB  - The aims of this study were to investigate the presence of genetic variation for
      susceptibility to pathogen-specific mastitis and to examine whether haplotypes of
      an identified quantitative trait locus with effect on unspecific mastitis
      resistance had different effects on specific mastitis pathogens. Bacteriological
      data on mastitis pathogens were obtained from the diagnostic laboratory at the
      Swedish National Veterinary Institute. The data were mainly from subclinical
      cases of mastitis but also clinical cases were included. Variance components were
      estimated for incidence of the six most frequent pathogens using Markov Chain
      Monte Carlo methodology via Gibbs sampling. Genetic variation for susceptibility
      to pathogen-specific mastitis was higher compared to estimates of general
      resistance to clinical mastitis in most other studies. However, because of the
      non-random nature of data collection, comparisons to other studies should be made
      by caution. The effect of haplotype on the risk of being infected by a given
      mastitis pathogen, relative to other pathogens, was studied using an allele
      substitution model. Although there were no significant haplotype substitution
      effects on the resistance to any of the six mastitis pathogens, there was a
      significant difference between the effects of two of the haplotypes regarding the
      risk of acquiring a Streptococcus dysgalactiae infection.

PMID- 22394236
TI  - Genomic selection strategies in dairy cattle: Strong positive interaction between
      use of genotypic information and intensive use of young bulls on genetic gain.
AB  - We tested the following hypotheses: (i) breeding schemes with genomic selection
      are superior to breeding schemes without genomic selection regarding annual
      genetic gain of the aggregate genotype (DeltaG(AG) ), annual genetic gain of the
      functional traits and rate of inbreeding per generation (DeltaF), (ii) a positive
      interaction exists between the use of genotypic information and a short
      generation interval on DeltaG(AG)  and (iii) the inclusion of an indicator trait
      in the selection index will only result in a negligible increase in DeltaG(AG) 
      if genotypic information about the breeding goal trait is known. We examined four
      breeding schemes with or without genomic selection and with or without intensive
      use of young bulls using pseudo-genomic stochastic simulations. The breeding goal
      consisted of a milk production trait and a functional trait. The two breeding
      schemes with genomic selection resulted in higher DeltaG(AG) , greater
      contributions of the functional trait to DeltaG(AG)  and lower DeltaF than the
      two breeding schemes without genomic selection. Thus, the use of genotypic
      information may lead to more sustainable breeding schemes. In addition, a short
      generation interval increases the effect of using genotypic information on
      DeltaG(AG) . Hence, a breeding scheme with genomic selection and with intensive
      use of young bulls (a turbo scheme) seems to offer the greatest potential. The
      third hypothesis was disproved as inclusion of genomically enhanced breeding
      values (GEBV) for an indicator trait in the selection index increased DeltaG(AG) 
      in the turbo scheme. Moreover, it increased the contribution of the functional
      trait to DeltaG(AG) , and it decreased DeltaF. Thus, indicator traits may still
      be profitable to use even when GEBV for the breeding goal traits are available.

PMID- 22394237
TI  - Genomic selection strategies in dairy cattle breeding programmes: Sexed semen
      cannot replace multiple ovulation and embryo transfer as superior reproductive
      technology.
AB  - The aim of this study was to test whether the use of X-semen in a dairy cattle
      population using genomic selection (GS) and multiple ovulation and embryo
      transfer (MOET) increases the selection intensity on cow dams and thereby the
      genetic gain in the entire population. Also, the dynamics of using different
      types of sexed semen (X, Y or conventional) in the nucleus were investigated. The
      stochastic simulation study partly supported the hypothesis as the genetic gain
      in the entire population was elevated when X-semen was used in the production
      population as GS exploited the higher selection intensity among heifers with
      great accuracy. However, when MOET was applied, the effect was considerably
      diminished as was the exchange of females between the nucleus and the production
      population, thus causing modest genetic profit from using X-sorted semen in the
      production population. In addition, the effect of using sexed semen on the
      genetic gain was very small compared with the effect of MOET and highly dependent
      on whether cow dams or bull dams were inseminated with sexed semen and on what
      type of semen that was used for the bull dams. The rate of inbreeding was seldom
      affected by the use of sexed semen. However, when all young bull candidates were
      born following MOET, the results showed that the use of Y-semen in the breeding
      nucleus tended to decrease the rate of inbreeding as it enabled GS to increase
      within-family selection. This implies that the benefit from using sexed semen in
      a modern dairy cattle breeding scheme applying both GS and MOET may be found in
      its beneficial effect on the rate of inbreeding.

PMID- 22394238
TI  - Validation of alternative models in genetic evaluation of racing performance in
      North Swedish and Norwegian cold-blooded trotters.
AB  - There have been several approaches to the estimation of breeding values of
      performance in trotters, and the objective of this study was to validate
      different alternatives for genetic evaluation of racing performance in the North
      Swedish and Norwegian cold-blooded trotters. The current bivariate approach with
      the traits racing status (RACE) and earnings (EARN) was compared with a threshold
      linear animal model and the univariate alternative with the performance trait
      only. The models were compared based on cross-validation of standardized
      earnings, using mean-squared errors of prediction (MSEP) and the correlation
      between the phenotype (Y) and the estimated breeding value (EBV). Despite
      possible effects of selection, a rather high estimate of heritability of EARN was
      found in our univariate analysis. The genetic trend estimate for EARN was clearly
      higher in the bivariate specification than in the univariate model, as a
      consequence of the considerable size of estimated heritability of RACE and its
      high correlation with EARN (approximately 0.8). RACE is highly influenced by
      ancestry rather than the on-farm performance of the horse itself. Consequently,
      the use of RACE in the genetic analysis may inflate the genetic trend of EARN
      because of a double counting of pedigree information. Although, because of the
      higher predictive ability of the bivariate specification, the improved ranking of
      animals within a year-class and the inability to discriminate between models for
      genetic trend, we propose to base prediction of breeding values on the current
      bivariate model.

PMID- 22394240
TI  - Probe of NH3 and CO adsorption on the very outermost surface of a porous TiO2
      adsorbent using photoluminescence spectroscopy.
AB  - We report the first measurements of the kinetics of adsorption on the very
      outermost surface sites of a porous material compared to measurements made of
      adsorption on the interior sites. NH(3) and CO were employed in this study as
      representative of slow diffusion and fast diffusion, respectively, through porous
      TiO(2). Adsorption of NH(3) at 200 K occurs mainly at the very near surface (~20
      nm) region as observed by photoluminescence (PL) spectroscopy, and its
      distribution by surface diffusion through the powder is highly retarded as judged
      by transmission IR spectroscopy. In contrast, the adsorption of CO in the near
      surface region at 120 K is followed by the fast distribution of CO by surface
      diffusion into TiO(2) powder, causing the near-surface CO coverage to lag behind
      the coverage in the bulk. In the desorption process, the near-surface region
      delivers adsorbed CO molecules into the gas phase, accompanied by the supply of
      diffusing CO molecules from the interior. As a result, the adsorption/desorption
      processes for CO in the near-surface region of porous TiO(2) show a pronounced
      hysteresis effect. As surface diffusion is retarded at lower temperatures, the
      hysteresis effect gradually disappears.

PMID- 22394239
TI  - Generation of candidate ligands for nicotinic acetylcholine receptors via in situ
      click chemistry with a soluble acetylcholine binding protein template.
AB  - Nicotinic acetylcholine receptors (nAChRs), which are responsible for mediating
      key physiological functions, are ubiquitous in the central and peripheral nervous
      systems. As members of the Cys loop ligand-gated ion channel family, neuronal
      nAChRs are pentameric, composed of various permutations of alpha (alpha2 to
      alpha10) and beta (beta2 to beta4) subunits forming functional heteromeric or
      homomeric receptors. Diversity in nAChR subunit composition complicates the
      development of selective ligands for specific subtypes, since the five binding
      sites reside at the subunit interfaces. The acetylcholine binding protein
      (AChBP), a soluble extracellular domain homologue secreted by mollusks, serves as
      a general structural surrogate for the nAChRs. In this work, homomeric AChBPs
      from Lymnaea and Aplysia snails were used as in situ templates for the generation
      of novel and potent ligands that selectively bind to these proteins. The
      cycloaddition reaction between building-block azides and alkynes to form stable
      1,2,3-triazoles was used to generate the leads. The extent of triazole formation
      on the AChBP template correlated with the affinity of the triazole product for
      the nicotinic ligand binding site. Instead of the in situ protein-templated azide
      alkyne cycloaddition reaction occurring at a localized, sequestered enzyme active
      center as previously shown, we demonstrate that the in situ reaction can take
      place at the subunit interfaces of an oligomeric protein and can thus be used as
      a tool for identifying novel candidate nAChR ligands. The crystal structure of
      one of the in situ-formed triazole-AChBP complexes shows binding poses and
      molecular determinants of interactions predicted from structures of known
      agonists and antagonists. Hence, the click chemistry approach with an in situ
      template of a receptor provides a novel synthetic avenue for generating candidate
      agonists and antagonists for ligand-gated ion channels.

PMID- 22394241
TI  - Effect of must characteristics on the diversity of Saccharomyces strains and
      their prevalence in spontaneous fermentations.
AB  - AIMS: The aim of this study was to investigate whether grapevine variety and must
      characteristics influence the diversity of Saccharomyces strains and their
      prevalence during spontaneous fermentations. METHODS AND RESULTS: Musts from
      different grapevine varieties, all of them autochthonous from Galicia, were used
      to perform spontaneous fermentations. Yeasts were isolated from the must and at
      the beginning, in the middle and at the end of fermentations. Those yeasts
      identified as Saccharomyces were characterized at the strain level by analysis of
      mtDNA-RFLP. The results showed a low diversity of Saccharomyces strains, which
      was related to must sugar content and total acidity. Moreover, from a total of 44
      different Saccharomyces strains, only eleven of them appeared at frequencies
      higher than 20% and were able to lead fermentations. A significant correlation
      between yeast strains and must acidity was observed, with the predominance of
      certain strains at high acidity values. CONCLUSIONS: Must characteristics, such
      as sugar content and acidity, influence the Saccharomyces strains diversity and
      the leader strains during fermentation. SIGNIFICANCE AND IMPACT OF THE STUDY:
      These results showed the adaptation of certain Saccharomyces strains to must with
      specific characteristics; this may be considered by winemakers for yeast inocula
      selection. Our findings have special relevance because this is the first study
      carried out in Galicia dealing with the influence of must properties on yeast
      strains that control fermentations.

PMID- 22394242
TI  - Effect of nanomaterials on the compound action potential of the shore crab,
      Carcinus maenas.
AB  - Little is known about the effects of manufactured nanomaterials on the function
      of nerves. The experiment aimed to test the effects of three different
      nanomaterials (1 mg l-1 of TiO2 NPs, Ag NPs or SWCNT) on the compound action
      potential of the shore crab (Carcinus maenas) compared with an appropriate bulk
      powder or metal salt control (bulk TiO2 powder, AgNO3 and carbon black
      respectively). In single action potential recordings, there were no effects of
      any of the nanomaterials on the peak amplitude, duration, rate of rise
      (depolarisation), or rate of decrease (repolarisation) of the compound action
      potential in crab saline, despite settling of each nanomaterial directly onto the
      nerve preparation. The ability of the crab nerve to be stimulated to tetanus was
      also unaffected by exposure to the nanomaterials compared with the appropriate
      bulk powder or metal salt control. Solvent controls with sodium dodecyl sulfate
      (SDS) also had no effect on action potentials. Overall, the study concludes that
      there were no effects of the materials at the concentrations tested on the
      compound action potential of the shore crab in physiological saline.

PMID- 22394243
TI  - A novel amino acid substitution of integrin alphaIIb in Glanzmann thrombasthenia
      confirms that the N-terminal region of the receptor plays a role in maintaining
      beta-propeller structure.
AB  - Mutation screening in Glanzmann thrombasthenia (GT) is now advanced. Despite the
      large number of genetic defects reported in the ITGA2B gene, few affect the
      structure of the N-terminal domain of the alphaIIb subunit. We now report a
      Catalan family where type I GT is given by compound heterozygosity within ITGA2B
      with a Gly13Val substitution in alphaIIb associated with a 13 bp deletion
      involving the splice site of exon 15. Molecular modelling confirmed that the
      Gly13Val mutation interfered with the structure of the alphaIIb beta-propeller
      and confirms that a fold-back of the N-terminus to interact with residues deep
      within the propeller is necessary for the normal intracellular processing of the
      maturing alphaIIbbeta3 integrin.

PMID- 22394244
TI  - Diffusion and partitioning of cations in an agarose hydrogel.
AB  - Self- and mutual diffusion were measured in a low-melt 1.5% agarose hydrogel as a
      function of ionic strength (0.1-100 mM) and pH (3-7) for Cd(2+) and a charged
      rhodamine derivative. Self-diffusion was measured by fluorescence correlation
      spectroscopy, whereas mutual diffusion was evaluated using a diffusion cell. In
      contrast to the results observed for the diffusion cell, self-diffusion of
      rhodamine 6G increased from 50 to 90% of that found in water as the ionic
      strength increased from 0.1 to 100 mM (pH = 6). The combined observations of
      decreasing diffusive flux in parallel with an increasing diffusion coefficient
      were attributed to the gel's Donnan potential. Donnan potentials obtained
      voltammetrically using a Au amalgam microelectrode varied from -30 to 0 mV as the
      ionic strength increased from 0.1 to 100 mM (pH = 6). At the low ionic strengths,
      Donnan potentials of this magnitude accounted for a 13* enhancement of Cd(2+)
      concentrations in the hydrogel, which was consistent with measurements obtained
      by a nitric acid extraction of the gel (15*) and able to explain the apparent
      discrepancy between mutual and self-diffusion measurements. The overall diffusion
      of the positively charged substrates decreased as the pH was decreased from 12 to
      3.

PMID- 22394245
TI  - First per-6-O-tritylation of cyclodextrins.
AB  - Because of the large dimension of the trityl group and the truncated conical
      geometry of cyclodextrin (CD) molecules, it is unclear if there is enough space
      at the narrower end of CDs to permit a per-6-O-tritylation. This work
      demonstrates that it is indeed possible to simultaneously install a trityl group
      at the O6-position of every glucopyranosyl unit in a CD. A novel per-6
      substitution method has been developed for CD chemistry.

PMID- 22394246
TI  - Nanoimprinted polymer solar cell.
AB  - Among the various organic photovoltaic devices, the conjugated polymer/fullerene
      approach has drawn the most research interest. The performance of these types of
      solar cells is greatly determined by the nanoscale morphology of the two
      components (donor/acceptor) and the molecular orientation/crystallinity in the
      photoactive layer. A vertically bicontinuous and interdigitized heterojunction
      between donor and acceptor has been regarded as one of the ideal structures to
      enable both efficient charge separation and transport. Synergistic control of
      polymer orientation in the nanostructured heterojunction is also critical to
      improve the performance of polymer solar cells. Nanoimprint lithography has
      emerged as a new approach to simultaneously control both the heterojunction
      morphology and polymer chains in organic photovoltaics. Currently, in the area of
      nanoimprinted polymer solar cells, much progress has been achieved in the
      fabrication of nanostructured morphology, control of molecular
      orientation/crystallinity, deposition of acceptor materials, patterned
      electrodes, understanding of structure-property correlations, and device
      performance. This review article summarizes the recent studies on nanoimprinted
      polymer solar cells and discusses the outstanding challenges and opportunities
      for future work.

PMID- 22394248
TI  - Glycophthalocyanines as photosensitizers for triggering mitotic catastrophe and
      apoptosis in cancer cells.
AB  - Photodynamic therapy (PDT) is a treatment modality for different forms of cancer
      based on the combination of light, molecular oxygen, and a photosensitizer (PS)
      compound. When activated by light, the PS generates reactive oxygen species
      leading to tumor destruction. Phthalocyanines are compounds that have already
      shown to be efficient PSs for PDT. Several examples of carbohydrate substituted
      phthalocyanines have been reported, assuming that the presence of carbohydrate
      moieties could improve their tumor selectivity. This work describes the
      photoeffects of symmetric and asymmetric phthalocyanines with D-galactose (so
      called GPh1, GPh2, and GPh3) on HeLa carcinoma cells and their involvement in
      cell death. Photophysical properties and in vitro photodynamic activities for the
      compounds considered revealed that the asymmetric glycophthalocyanine GPh3 is
      very efficient and selective, producing higher photocytotoxicity on cancer cells
      than in nonmalignat HaCaT. The cell toxiticy after PDT treatment was dependent
      upon light exposure level and GPh3 concentration. GPh3 causes cell cycle arrest
      at the metaphase stage leading to multiple spindle poles, mitotic catastrophe,
      followed by apoptosis in cancer cells. These effects were partially negated by
      the pancaspase inhibitor Z-VAD-FMK. Together, these results indicate that GPh3 is
      an excellent candidate drug for PDT, able to induce selective tumor cell death.

PMID- 22394247
TI  - Detection of LIM domain only 2 (LMO2) in normal human tissues and haematopoietic
      and non-haematopoietic tumours using a newly developed rabbit monoclonal
      antibody.
AB  - AIMS: We describe a new rabbit monoclonal antibody, raised against a fixation
      resistant epitope of the transcription regulator LIM domain only 2 (LMO2).
      METHODS AND RESULTS: Lymphoma cell lines and a large series of normal and
      neoplastic samples were investigated by Western blot and immunohistochemistry.
      The antibody detected nuclear positivity for the protein, with the exception of a
      proportion of classical Hodgkin lymphomas (HLs), peripheral T cell lymphomas
      (PTCLs) and solid tumours that showed granular cytoplasmic staining. In normal
      lympho-haematopoietic tissues, LMO2 was expressed at different intensities by
      CD34(+) blasts, haematopoietic precursors, germinal centre (GC), mantle and
      splenic marginal zone B cells. While reactive with only scattered elements in the
      thymus and nine of 237 PTCLs, the antibody stained 31 of 39 T-acute lymphoblastic
      lymphoma/leukaemias (T-ALLs) and the T-ALL-derived human leukaemic cell line,
      CCRF-CEM. LMO2 was found in 88% of B-acute lymphoblastic lymphoma/leukaemias (B
      ALLs), 5% chronic lymphocytic leukaemias (CLLs) and 14%, 57% and 41% of mantle,
      follicular and Burkitt lymphomas, respectively. In the setting of diffuse large B
      cell lymphomas (DLBCLs), LMO2-positivity was related strongly to a GC phenotype.
      LMO2 was found in 83% primary mediastinal large B cell lymphomas (PMBLs) and 100%
      nodular lymphocyte predominant Hodgkin lymphomas (NLPHLs), whereas only 10% of
      classical HLs were stained. Acute and chronic myeloid leukaemias were usually
      positive. CONCLUSIONS: The new anti-LMO2 antibody can be applied confidently to
      routine sections, contributing to the differential diagnosis of several lymphoma
      subtypes, subtyping of DLBCLs and potential development of innovative therapies.

PMID- 22394249
TI  - Esophageal solid bolus transit: studies using combined multichannel intraluminal
      impedance and manometry in healthy volunteers.
AB  - The purpose of this study is to apply combined multichannel intraluminal
      impedance and esophageal manometry (MII-EM) to test esophageal function during
      solid swallowing in a normal healthy population. We determined whether combined
      MII-EM with solid bolus is more sensitive than that with viscous bolus in the
      detection of motility abnormality. Eighteen healthy volunteers (11 men and 7
      women; mean age 22 years, range 20-26 years) underwent combined MII-EM with a
      catheter containing four impedance-measuring segments and five solid-state
      pressure transducers. Each subject received 10 viscous and 10 solid materials.
      Tracings were analyzed manually for bolus presence time, total bolus transit
      time, contraction amplitude, duration, and onset velocity. Three hundred and
      sixty swallows including viscous and solid materials were analyzed. Contraction
      amplitude for the viscous swallows was higher at 20 cm above the lower esophageal
      sphincter (LES) (P= 0.049) but lower at 15 cm above the LES (P < 0.001). Duration
      of contractions for the solid swallows was longer at 15 cm (P= 0.002) and 10 cm
      above the LES (P= 0.011) compared with viscous swallows. The total bolus transit
      time for solid was significantly shorter than that for viscous boluses (6.8 vs.
      7.7 seconds, P < 0.001). Bolus presence time appeared to be similar between
      viscous and solid boluses (except in the proximal esophagus). The percentage of
      swallows with ineffective peristalsis by manometry, as well as those with
      incomplete bolus transit by impedance, did not differ between viscous and solid
      swallows. The proportion of manometrically ineffective solid swallows with
      incomplete bolus transit was greater than that of viscous swallows (62.1% vs.
      34.8%, P= 0.05). Application of solid boluses may potentially enhance diagnostic
      capability of esophageal function testing. Solid boluses can be regarded as a
      valuable complement to viscous boluses in the detection of esophageal motility
      abnormalities when applied with combined MII-EM.

PMID- 22394251
TI  - Experimental test of the effects of a non-native invasive species on a wintering
      shorebird.
AB  - The abundance of nearly one-quarter of the world's shorebird species is
      declining. At the same time, the number of non-native species in coastal
      ecosystems is increasing rapidly. In some cases, non-native species may affect
      negatively the abundance and diversity of shorebird prey species. We conducted an
      experimental study of the effects of the introduced European green crab (Carcinus
      maenas) on prey consumption by wintering Dunlin (Calidris alpina) in a central
      California estuary. We placed green crabs and Dunlin sequentially in field
      enclosures and measured changes in density of benthic invertebrate prey (e.g.
      polychaetes and small clams), Dunlin biomass, and gut contents of both Dunlin and
      crabs and observed foraging behavior of Dunlin. Green crabs significantly
      affected Dunlin foraging success through both direct and indirect multitrophic
      linkages. In enclosures with high densities of green crabs, crab foraging reduced
      the availability of polychaetes, and Dunlin consumed significantly fewer
      polychaetes compared with Dunlin in enclosures without crabs. High densities of
      green crabs were also associated with increased availability of small clams.
      Dunlin consumed significantly more small clams compared with Dunlin in enclosures
      without crabs. In our literature survey of studies of effects of non-native
      invasive species on shorebirds, we found three prior experiments that addressed
      the effect of non-native invasive species on shorebirds. Results of two of these
      studies showed positive direct effects of non-native invertebrates on shorebirds,
      1 showed negative direct effects of a non-native plant on shorebirds through
      habitat conversion, and none showed indirect effects of non-native invertebrates.
      We suggest future management of shorebirds explicitly examine how non-native
      marine species, particularly invertebrates, directly and indirectly affect
      shorebirds.

PMID- 22394250
TI  - Gonadal hormones and oxidative stress interaction differentially affects survival
      of male and female mice after lung Klebsiella pneumoniae infection.
AB  - Survival of mice after Klebsiella pneumoniae infection and phagocytosis by
      alveolar macrophages (AMs), in the presence or absence of ozone (O(3)) exposure
      prior to infection, is sex dependent. The objective of this work was to study the
      role of gonadal hormones, 5alpha-dihydrotestosterone (DHT) and 17beta-estradiol
      (E(2)), on mouse survival after filtered air (FA) or O(3) exposure.
      Gonadectomized female (G*F) and male (G*M) mice implanted with control or hormone
      pellets (DHT in G*F, or E(2) in G*M), exposed to O(3) (2 ppm, 3h) or FA, and
      infected with K. pneumoniae were monitored for survival. Survival in G*F was
      identical after FA or O(3) exposure; in G*M O(3) exposure resulted in lower
      survival compared to FA. In O(3)-exposed females, gonadectomy resulted in
      increased survival compared to intact females or to G*M+E(2). A similar effect
      was observed in G*F+DHT. The combined negative effect of oxidative stress and
      hormone on survival was higher for E(2). Gonadectomy eliminated (females) or
      minimized (males) the previously observed sex differences in survival in response
      to oxidative stress, and hormone treatment restored them. These findings indicate
      that gonadal hormones and/or oxidative stress have a significant effect on mouse
      survival.

PMID- 22394252
TI  - Simulation of chemical metabolism for fate and hazard assessment. IV. Computer
      based derivation of metabolic simulators from documented metabolism maps.
AB  - Computer simulation of xenobiotic metabolism and degradation is usually performed
      proceeding from a set of expert-developed rules modelling the actual enzyme
      driven chemical reactions. With the accumulation of extensive metabolic pathway
      data, the analysis required to derive such chemical reaction patterns has become
      more objective, but also more convoluted and demanding. Herein we report on our
      computer-based approach for the analysis of metabolic maps, leading to the
      construction of reaction rules statistically suitable for simulation purposes. It
      is based on the set of so-called bare transformations which encompass all unique
      reaction patterns as obtained by a heuristically enhanced maximum common subgraph
      algorithm. The bare transformations guarantee that no existing metabolite is
      missed in simulation at the expense of an enormous amount of false positive
      predictions. They are rendered more selective by correlating the generated true
      and false positives to the locations of typical chemical functional groups in the
      potential reactants. The approach and its results are illustrated for a metabolic
      map collection of 15 cycloalkanes.

PMID- 22394253
TI  - An activity-based probe reveals dynamic protein-protein interactions mediating
      IGF-1R transactivation by the GABA(B) receptor.
AB  - Many GPCRs (G-protein-coupled receptors) can activate RTKs (receptor tyrosine
      kinases) in the absence of RTK ligands, a phenomenon called transactivation.
      However, the underlying molecular mechanisms remain undefined. In the present
      study we investigate the molecular basis of GABA(B) (gamma-aminobutyric acid B)
      receptor-mediated transactivation of IGF-1R (insulin-like growth factor type I
      receptor) in primary neurons. We take a chemical biology approach by developing
      an activity-based probe targeting the GABA(B) receptor. This probe enables us
      first to lock the GABA(B) receptor in an inactive state and then activate it with
      a positive allosteric modulator, thereby permitting monitoring of the dynamic of
      the protein complex associated with IGF-1R transactivation. We find that
      activation of the GABA(B) receptor induces a dynamic assembly and disassembly of
      a protein complex, including both receptors and their downstream effectors. FAK
      (focal adhesion kinase), a non-RTK, plays a key role in co-ordinating this
      dynamic process. Importantly, this dynamic of the GABA(B) receptor-associated
      complex is critical for transactivation and transactivation-dependent neuronal
      survival. The present study has identified an important mechanism underlying GPCR
      transactivation of RTKs, which was enabled by a new chemical biology tool
      generally applicable for dissecting GPCR signalling.

PMID- 22394254
TI  - Verbal fluency and awareness of functional deficits in early-stage dementia.
AB  - Assessment of activities of daily living is an important element in the diagnosis
      of dementia, with research suggesting a link between functional ability and
      cognition. We investigated the relationship between self- and informant ratings
      of instrumental activities of daily living (iADL) and verbal executive
      functioning in early-stage dementia. A total of 96 people with early-stage
      Alzheimer's disease or vascular or mixed dementia and their carers completed the
      Functional Activities Questionnaire; people with dementia also completed a test
      of letter fluency. Letter fluency was associated with self-ratings of iADL, while
      informant ratings of iADL were associated with the age and Mini-Mental State
      Examination score of the person with dementia. Self-ratings of perceived
      functioning suggested significantly less impairment than informant ratings. Those
      with impaired letter fluency rated themselves as having greater difficulties in
      iADLs than those who performed better. People with early-stage dementia vary in
      their subjective level of awareness of their iADL functioning, and difficulties
      with language production may contribute to better awareness of iADL impairments.

PMID- 22394255
TI  - Prebiotics enhance magnesium absorption and inulin-based fibers exert chronic
      effects on calcium utilization in a postmenopausal rodent model.
AB  - Age-related changes in calcium metabolism play a role in the development of
      osteoporosis. A 4-wk feeding study was conducted in 5-mo-old ovariectomized (OVX)
      Sprague-Dawley rats to assess the effect of various dietary fibers on mineral
      metabolism and bone health parameters. There were 6 treatment groups: sham
      Control, OVX-Control, OVX rats receiving daily estradiol (E2) injections, and OVX
      rats receiving an AIN-93M diet supplement with either an inulin-based fiber
      (Synergy1(r) or Fruitafit HD(r)) or a novel fiber (polydextrose) at 5% wt. of
      diet. Calcium and magnesium metabolic balances were performed after early (3 d)
      and late exposure (4 wk) to dietary treatments. Rats receiving polydextrose had
      significantly higher net calcium absorption efficiency and retention than all
      control groups and a trend (P<= 0.10) for higher calcium absorption when compared
      to inulin-based fibers after early exposure but the advantage did not persist
      over long-term exposure. The inulin-based fibers had positive chronic effects on
      calcium metabolism that were related to changes in the gut, that is, production
      of short chain fatty acids and higher cecal wall weights. All fibers improved
      magnesium absorption and retention in early and late metabolic balances; effects
      on magnesium metabolism were more pronounced than for calcium. PRACTICAL
      APPLICATION: Steady growth in US middle-aged and elderly populations has led to
      higher incidences of several chronic diseases including osteoporosis, a bone
      disease that primarily affects postmenopausal women. Recent research suggests
      that certain dietary fibers (prebiotics) enhance mineral absorption and may
      impart bone health benefits. This work examines the impact of prebiotic
      supplementation on mineral metabolism and bone health using a postmenopausal rat
      model. Study findings will aid future investigations in ascertaining the factors
      related to potential bone health benefits of prebiotic which will aid in
      developing an effective prebiotics food product/supplement that will address the
      bone health needs of consumers.

PMID- 22394257
TI  - Removal of patulin from apple juice using inactivated lactic acid bacteria.
AB  - AIMS: Apples and apple products are the most notably commodities contaminated
      with patulin (PAT), which cause detrimental effects on human health and economic
      problems. The primary objective of this study was to investigate the removal of
      PAT contamination from apple juice using 10 different inactivated lactic acid
      bacteria (LAB) strains. METHODS AND RESULTS: Significant quantities of PAT
      ranging from 47 to 80% were bound to all tested bacterial strains, whereas
      Lactobacillus rhamnosus 6224 and Enterococcus faecium 21605 caused a decrease of
      PAT by 80.4 and 64.5%, respectively. The results showed that the binding of PAT
      depends on the initial concentration of toxin and the adsorption temperature,
      also the differences in biomass existed among the 10 bacterial strains. IR
      analysis was performed to identify potential functional groups and the possible
      binding sites related to PAT adsorption. CONCLUSIONS: The removal of PAT was
      observed to be strain specific. The results indicated that the biosorption
      process did not affect the quality of juice. FTIR analysis showed that the cell
      wall plays a key role in PAT adsorption. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Our results proof that inactivated LAB have the potential as a novel and
      promising adsorbent to bind PAT effectively.

PMID- 22394258
TI  - A review of risk perceptions and other factors that influence flood mitigation
      behavior.
AB  - In flood risk management, a shift can be observed toward more integrated
      approaches that increasingly address the role of private households in
      implementing flood damage mitigation measures. This has resulted in a growing
      number of studies into the supposed positive relationship between individual
      flood risk perceptions and mitigation behavior. Our literature review shows,
      however, that, actually, this relationship is hardly observed in empirical
      studies. Two arguments are provided as an explanation. First, on the basis of
      protection motivation theory, a theoretical framework is discussed suggesting
      that individuals' high-risk perceptions need to be accompanied by coping
      appraisal to result in a protective response. Second, it is pointed out that
      possible feedback from already-adopted mitigation measures on risk perceptions
      has hardly been considered by current studies. In addition, we also provide a
      review of factors that drive precautionary behavior other than risk perceptions.
      It is found that factors such as coping appraisal are consistently related to
      mitigation behavior. We conclude, therefore, that the current focus on risk
      perceptions as a means to explain and promote private flood mitigation behavior
      is not supported on either theoretical or empirical grounds.

PMID- 22394259
TI  - Alemtuzumab as compared to alternative contemporary induction regimens.
AB  - Between 1 January 2002 and 31 December 2007, our center performed 1687 adult
      renal transplants. A retrospective analysis was performed to compare outcomes
      between patients receiving alemtuzumab (n = 632) and those receiving either
      basiliximab (n = 690) or thymoglobulin (n = 125). Patients receiving alemtuzumab
      were younger (49 vs. 51 years, P = 0.02), had fewer HLA matches (1.7 vs. 2.0, P <
      0.0001), were more likely to have a cytomegalovirus (CMV) donor(+)/recipient(-)
      transplant (22% vs. 17%, P = 0.03) and were less likely to receive a living donor
      allograft (32% vs. 37%, P = 0.04). Alemtuzumab recipients were less likely to
      receive tacrolimus (35% vs. 47%, P < 0.0001). The 1-, 3-, and 5-year cumulative
      incidence of antibody-mediated rejection (AMR) in alemtuzumab-treated patients
      was 19%, 24%, and 27%, vs. 11%, 15%, and 18% for the other group (P < 0.0001).
      The 1-, 3-, and 5-year allograft survival in the alemtuzumab group was 88%, 75%,
      and 67%, vs. 91%, 82%, and 74% for the other group (P < 0.0001). Patient survival
      was equivalent. Alemtuzumab was an independent risk factor for living donor
      allograft loss (HR 2.0, P = 0.004), opportunistic infections (HR 1.3, P = 0.01),
      CMV infections (HR 1.6, P = 0.001), and AMR (HR 1.5, P = 0.002). The
      significantly worse graft survival in the alemtuzumab cohort may be due to the
      increased rates of AMR and infectious complications.

PMID- 22394260
TI  - Short communication: adhesion pathways utilized by HIV-infected lymphocytes.
AB  - We recently reported a novel adhesion pathway in lymphocytes that is mediated by
      cyclin-dependent kinase (Cdk) 4 activity and mediates lymphocyte interactions
      with endothelial matrix. We now demonstrate that HIV-infected lymphocytes also
      use Cdk4 to mediate spontaneous adhesion to fibronectin and endothelial matrix.
      We further demonstrate that HIV-infected lymphocytes require Rap-1 activity for
      phorbol-stimulated adhesion. Understanding adhesion pathways used by HIV-infected
      lymphocytes may lead to interventions to regulate aberrant adhesion and
      migration.

PMID- 22394262
TI  - One-step, multiplexed fluorescence detection of microRNAs based on duplex
      specific nuclease signal amplification.
AB  - Traditional molecular beacons, widely applied for detection of nucleic acids,
      have an intrinsic limitation on sensitivity, as one target molecule converts only
      one beacon molecule to its fluorescent form. Herein, we take advantage of the
      duplex-specific nuclease (DSN) to create a new signal-amplifying mechanism,
      duplex-specific nuclease signal amplification (DSNSA), to increase the detection
      sensitivity of molecular beacons (Taqman probes). DSN nuclease is employed to
      recycle the process of target-assisted digestion of Taqman probes, thus,
      resulting in a significant fluorescence signal amplification through which one
      target molecule cleaves thousands of probe molecules. We further demonstrate the
      efficiency of this DSNSA strategy for rapid direct quantification of multiple
      miRNAs in biological samples. Our experimental results showed a quantitative
      measurement of sequence-specific miRNAs with the detection limit in the
      femtomolar range, nearly 5 orders of magnitude lower than that of conventional
      molecular beacons. This amplification strategy also demonstrated a high
      selectivity for discriminating differences between miRNA family members.
      Considering the superior sensitivity and specificity, as well as the multiplex
      and simple-to-implement features, this method promises a great potential of
      becoming a routine tool for simultaneously quantitative analysis of multiple
      miRNAs in tissues or cells, and supplies valuable information for biomedical
      research and clinical early diagnosis.

PMID- 22394261
TI  - Influence of simulated gastrointestinal conditions on particle-induced
      cytotoxicity and interleukin-8 regulation in differentiated and undifferentiated
      Caco-2 cells.
AB  - Novel aspects of engineered nanoparticles offer many advantages for optimising
      food products and packaging. However, their potential hazards in the
      gastrointestinal tract require further investigation. We evaluated the toxic and
      inflammatory potential of two types of particles that might become increasingly
      relevant to the food industry, namely SiO2 and ZnO. The materials were
      characterised for their morphology, oxidant generation and hydrodynamic
      behaviour. Cytotoxicity and interleukin-8 mRNA and protein expression were
      evaluated in human intestinal Caco-2 cells. Particle pretreatment under simulated
      gastric and intestinal pH conditions resulted in reduced acellular ROS formation
      but did not influence cytotoxicity (WST-1 assay) or IL-8 expression. However, the
      differentiation status of the cells markedly determined the cytotoxic potency of
      the particles. Further research is needed to determine the in vivo relevance of
      our current observations regarding the role of particle aggregation and the stage
      of intestinal epithelial cell differentiation in determining the hazards of
      ingested particles.

PMID- 22394263
TI  - Plasmonic nanoparticle networks for light and heat concentration.
AB  - Self-assembled plasmonic nanoparticle networks (PNN) composed of chains of 12 nm
      diameter crystalline gold nanoparticles exhibit a longitudinally coupled plasmon
      mode centered at 700 nm. We have exploited this longitudinal absorption band to
      efficiently confine light fields and concentrate heat sources in the close
      vicinity of these plasmonic chain networks. The mapping of the two phenomena on
      the same superstructures was performed by combining two-photon luminescence and
      fluorescence polarization anisotropy imaging techniques. Besides the light and
      heat concentration, we show experimentally that the planar spatial distribution
      of optical field intensity can be simply modulated by controlling the linear
      polarization of the incident optical excitation. On the contrary, the heat
      production, which is obtained here by exciting the structures within the
      optically transparent window of biological tissues, is evenly spread over the
      entire PNN. This contrasts with the usual case of localized heating in continuous
      nanowires, thus opening opportunities for these networks in light-induced
      hyperthermia applications. Furthermore, we propose a unified theoretical
      framework to account for both the nonlinear optical and thermal near-fields
      around PNN. The associated numerical simulations, based on a Green's function
      formalism, are in excellent agreement with the experimental images. This
      formalism therefore provides a versatile tool for the accurate engineering of
      optical and thermodynamical properties of complex plasmonic colloidal
      architectures.

PMID- 22394264
TI  - Characterization of highly unusual NH+-O hydrogen bonding to ester ether oxygen
      atoms through spectroscopic and computational studies.
AB  - We characterize a highly unusual, charged NH-O hydrogen bond formed within esters
      of 8-(dimethylamino)naphthalen-1-ol in which an ammonium ion serves as an
      intramolecular hydrogen bond donor to spatially proximate ester ether oxygen
      atoms. Infrared spectroscopic analysis of the ester carbonyl frequencies
      demonstrates significant blue-shifting when ether hydrogen bonding is possible,
      in stark contrast to the more commonly observed red shift that occurs upon
      hydrogen bonding to the ester carbonyl oxygen. The intrinsic behavior of the
      linkage (i.e., in which counterions and solvent effects are eliminated) is
      provided by vibrational predissociation spectroscopy of the isolated gas-phase
      cations complexed with weakly bound D(2) molecules.

PMID- 22394265
TI  - Identification of a gamma-irradiated ingredient (garlic powder) in Korean
      barbeque sauce by thermoluminescence analysis.
AB  - Thermoluminescence (TL) analysis was applied to identify gamma-irradiated garlic
      powder in Korean barbeque sauce before and after pasteurization (85  degrees C,
      30 min), when blended in different ratios (1%, 3%, and 5%). The sauce sample with
      nonirradiated garlic powder gave a background glow curve. However, the sample
      blended with irradiated ingredient (1 and 10 kGy) showed typical TL glow curves
      at temperatures of 150 to 200  degrees C. The identification properties of sauce
      samples were more influenced by blending ratios than by irradiation doses,
      showing that 3% and 5% added samples produced glow curves at 150 to 250  degrees
      C. After pasteurization of the samples containing the irradiated ingredient, TL
      glow intensity decreased but did not change its shape or temperature range. As a
      result, the pasteurization of Barbeque sauces containing irradiated ingredients
      had reduced TL glow intensity, but the shape and temperature range of glow curve
      were still able to provide information required for confirming irradiation
      treatment. PRACTICAL APPLICATION: To monitor the irradiated food in international
      market, thermoluminescence (TL) analysis is considered most promising
      identification technique because of its sensitivity and long-term stability. In
      this study the applicability of TL analysis to detect an irradiated ingredient
      (garlic powder) added in low quantity to a food matrix (sauce) was investigated.
      The effect of processing (pasteurization) on TL results was also evaluated.

PMID- 22394266
TI  - Impaired long-term potentiation and long-term memory deficits in xCT-deficient
      sut mice.
AB  - xCT is the functional subunit of the cystine/glutamate antiporter system xc-,
      which exchanges intracellular glutamate with extracellular cystine. xCT has been
      reported to play roles in the maintenance of intracellular redox and ambient
      extracellular glutamate, which may affect neuronal function. To assess a
      potential role of xCT in the mouse hippocampus, we performed fear conditioning
      and passive avoidance for long-term memories and examined hippocampal synaptic
      plasticity in wild-type mice and xCT-null mutants, sut mice. Long-term memory was
      impaired in sut mice. Normal basal synaptic transmission and short-term
      presynaptic plasticity at hippocampal Schaffer collateral-CA1 synapses were
      observed in sut mice. However, LTP (long-term potentiation) was significantly
      reduced in sut mice compared with their wild-type counterparts. Supplementation
      of extracellular glutamate did not reverse the reduction in LTP. Taken together,
      our results suggest that xCT plays a role in the modulation of hippocampal long
      term plasticity.

PMID- 22394267
TI  - VEGF levels in humans and animal models with RDS and BPD: temporal relationships.
AB  - Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD)
      contribute significantly to neonatal morbidity and mortality. Pulmonary function
      depends on the interaction between alveolar microvasculature and airspace
      development. While it has been shown in various animal models that vascular
      endothelial growth factor (VEGF) and its receptors increase in normal animal lung
      development, its pathophysiological role in neonatal respiratory failure is not
      yet entirely clear. Current animal and human studies exhibit controversial
      results. Though animal models are invaluable tools in the study of human lung
      disease, inherent differences in physiology mandate clarification of the timing
      of these studies to ensure that they appropriately correlate with the human
      stages of lung development. The purpose of this review article is to highlight
      the importance of considering the temporal relationship of VEGF and lung
      development in human neonates and developmentally-appropriate animal models with
      RDS and BPD.

PMID- 22394268
TI  - Eosinophilic infiltration of the esophagus following endoscopic ablation of
      Barrett's neoplasia.
AB  - To assess the incidence of esophageal intra-epithelial eosinophilic infiltration
      following endoscopic ablation of Barrett's esophagus (BE), a retrospective study
      of consecutive cases of endoscopic ablation of BE with dysplasia or cancer using
      radiofrequency ablation (RFA) and spray cryotherapy at two centers in the United
      States was performed. Post-ablation eosinophilia was defined as >= 5 eosinophils
      per high power field during post-treatment surveillance. Twenty of 122 patients
      (16%) undergoing ablation developed esophageal eosinophilia after ablation,
      including 8/77 (10%) treated with RFA and 12/44 (27%) treated with cryotherapy.
      No patient had clinical or endoscopic findings of or risk factors for
      eosinophilic esophagitis. Esophageal eosinophilia persisted in 30% over a median
      of 20.2 months. On multivariate analysis, post-ablation eosinophilia was
      independently associated with increasing BE segment length (adjusted odds ratio
      1.46 for every 2-cm increase, 95% confidence interval 1.24-1.71) and cryotherapy
      as the ablation modality (adjusted odds ratio 5.23, 95% confidence interval 1.67
      16.39). Esophageal eosinophilic infiltration after endoscopic ablation with RFA
      and cryotherapy is common and is associated with the BE segment length and
      treatment modality. The clinical significance of post-ablation eosinophilia is
      unclear.

PMID- 22394269
TI  - Antibody-mediated kidney allograft rejection: therapeutic options and their
      experimental rationale.
AB  - With the advent of novel therapies to directly intervene with B cell immunity and
      complement activation, antibody-mediated kidney allograft rejection (AMR) has
      come into the focus of transplant immunologists. Intravenous immunoglobulin,
      rituximab, bortezomib, and eculizumab have been used to treat patients with acute
      AMR, apart from the standard treatment of antibody removal with plasma exchange
      or immunoadsorption and steroid pulses. This article describes the experimental
      rationale and summarizes the still limited clinical experience with these novel
      therapies in the transplant setting. Results with the standard treatment for
      acute AMR, including intense plasmapheresis, intravenous immunoglobulins, and
      steroids are good with a graft survival of 80% at 18 months. In contrast,
      patients suffering from chronic AMR have significant irreversible damage in their
      grafts with substantially impaired graft survival. Thus, the authors propose a
      step-wise escalation of therapy in refractory cases of acute AMR and advocate an
      urgent need for controlled therapeutic trials for acute and chronic AMR not to
      inflict unnecessary harm on our patients by uncontrolled polypragmasy.

PMID- 22394270
TI  - Placental weight and neurologic outcome in the infant: a review.
AB  - OBJECTIVE: To review the agreement of published standards on placental weights
      (PW) and fetal-placental (F/P) ratios, examine factors contributing to PW and ask
      whether aberrant placental weight is associated with adverse neurologic outcome.
      METHODS: We conducted a literature search for standards of PW, F/P ratio and the
      relationship of PW to perinatal death, neonatal encephalopathy or cerebral palsy.
      We reviewed 17 studies of normative PW and 10 of F/P ratios. Since 1990, seven
      studies compared mean and extreme percentile bounds between 35 and 42 weeks of
      gestation. Nine publications examined PW and neurologic outcome. RESULTS:
      Untrimmed placentas were heavier by 131-193 g. F/P ratios differed by 0.2-2.34
      between trimmed and untrimmed placentas. Fresh, frozen or fixed preparation prior
      to weighing had minimal effect on weight. Gender and race had negligible affect.
      Placentas from caesarean sections averaged 75 g heavier than vaginal deliveries.
      There were no consistent associations of aberrant PW and neurologic outcome.
      CONCLUSIONS: Reference standards of recent studies on trimmed placentas were
      largely in agreement. Current findings relating aberrant PW and adverse
      neurologic outcome are inconclusive. Further study of the relationship between
      placental weight and neonatal encephalopathy or cerebral palsy is warranted, in
      representative populations using within-study controls.

PMID- 22394271
TI  - Risk factors for relaparotomy after cesarean section.
AB  - OBJECTIVE: To investigate risk factors for relaparotomy after cesarean section
      (CS). METHODS: A retrospective case-control study comparing all CS that were
      complicated with relaparotomy to cesarean deliveries without this complication.
      RESULTS: Relaparotomy complicated 0.23% (n=80) of CS during the study period
      (n=34,389). Independent risk factors for relaparotomy following CS from a
      multivariable logistic regression model were post partum hemorrhage, cervical
      tears, placenta previa, uterine rupture, placental abruption, severe preeclampsia
      and previous CS. Most women (51.2%) underwent relaparotomy during the first 24 h
      after CS. The leading causes for relaparotomy was bleeding (70%) and burst
      abdomen (8.8%). Hysterectomy was performed in 31.3% of the patients. CONCLUSION:
      Risk factors for relaparotomy after CS are previous CS, severe preeclampsia,
      placenta previa, uterine rupture, placental abruption, cervical tear and PPH.
      Experienced obstetricians should be involved in such cases and the possibility
      for complications including relaparotomy should be emphasized.

PMID- 22394272
TI  - Cell viability and immunostimulating and protective capacities of Bifidobacterium
      longum 51A are differentially affected by technological variables in fermented
      milks.
AB  - AIM: To investigate the cell viability of Bifidobacterium longum 5(1A) in
      fermented milks and to study its immunostimulating and protective capacity
      against Salmonella enterica ssp. enterica serovar Typhimurium infection in mice.
      METHODS AND RESULTS: Bifidobacterium longum 5(1A) was added to milk fermented
      with different yoghurt starter cultures, before or after fermentation, and
      viability was monitored during storage (5 degrees C, 28 days). Resistance to
      simulated gastric acid digestion was assessed. Fermented milks were orally
      administered to mice for 10 days followed by oral infection with Salmonella
      Typhimurium. The number of IgA+ cells in the small and large intestine was
      determined before infection. Survival to infection was monitored for 20 days.
      Bifidobacterium longum 5(1A) lost viability during storage, but the product
      containing it was effective for the induction of IgA+ cells proliferation in the
      gut and for the protection of mice against Salm. Typhimurium infection.
      CONCLUSIONS: Cell viability of Bif. longum 5(1A) in fermented milks along storage
      did not condition the capacity of the strain to enhance the number of IgA+ cells
      in the gut and to protect mice against Salmonella infection. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The uncoupling of cell viability and functionality
      demonstrated that, in certain cases, nonviable cells can also exert positive
      effects.

PMID- 22394273
TI  - An asymmetric synthesis of L-pyrrolysine.
AB  - An efficient asymmetric synthesis of the 22nd amino acid L-pyrrolysine has been
      accomplished. The key stereogenic centers were installed by an asymmetric
      conjugate addition reaction. A Staudinger/aza-Wittig cyclization was used to form
      the acid-sensitive pyrroline ring. Pyrrolysine was synthesized in 13 steps in 20%
      overall yield.

PMID- 22394274
TI  - "You are so beautiful"*: behind women's attractiveness towards the biology of
      reproduction: a narrative review.
AB  - Female beauty has always attracted human beings. In particular, beauty has been
      interpreted in terms of reproductive potential and advantage in selection of
      mates. We have reviewed the recent literature on female facial and physical
      beauty with the objective of defining which parameters could influence female
      attractiveness. Symmetry, averageness, and sexual dimorphism with regards to
      facial beauty, as well as waist-to-hip ratio (WHR), breast size, and body mass
      index (BMI) for physical beauty, have been assessed. In current societies, it
      appears that facial attractiveness results from a mixture of symmetry and
      averageness of traits, high forehead and cheekbones, small nose and chin, full
      lips, thin eyebrows, and thick hair. A low WHR reliably characterized physical
      attractiveness, whereas inconsistencies have been observed in the evaluation of
      breast size and BMI. The importance of breast size appears to vary with time and
      sex of evaluators, whereas the impact of BMI is related to socio-economic
      conditions. The various hypotheses behind beauty and the role of attractiveness
      in mate choice and sexual selection are here described in terms of continuation
      of human species. Intriguing associations are emerging between features of
      attractiveness and some reproductive disorders, as both are substantially
      influenced by sex steroid hormones.

PMID- 22394275
TI  - Hunting, law enforcement, and African primate conservation.
AB  - Primates are regularly hunted for bushmeat in tropical forests, and systematic
      ecological monitoring can help determine the effect hunting has on these and
      other hunted species. Monitoring can also be used to inform law enforcement and
      managers of where hunting is concentrated. We evaluated the effects of law
      enforcement informed by monitoring data on density and spatial distribution of 8
      monkey species in Tai National Park, Cote d'Ivoire. We conducted intensive
      surveys of monkeys and looked for signs of human activity throughout the park. We
      also gathered information on the activities of law-enforcement personnel related
      to hunting and evaluated the relative effects of hunting, forest cover and
      proximity to rivers, and conservation effort on primate distribution and density.
      The effects of hunting on monkeys varied among species. Red colobus monkeys
      (Procolobus badius) were most affected and Campbell's monkeys (Cercopithecus
      campbelli) were least affected by hunting. Density of monkeys irrespective of
      species was up to 100 times higher near a research station and tourism site in
      the southwestern section of the park, where there is little hunting, than in the
      southeastern part of the park. The results of our monitoring guided law
      enforcement patrols toward zones with the most hunting activity. Such systematic
      coordination of ecological monitoring and law enforcement may be applicable at
      other sites.

PMID- 22394277
TI  - Characterization and analyses of acid-extractable and leached trace elements in
      dental cements.
AB  - AIMS: Determination of the elemental constitution and investigation of the total
      and leachable arsenic, chromium and lead in Portland cement, pure tricalcium
      silicate, Biodentine, Bioaggregate and mineral trioxide aggregate (MTA) Angelus.
      METHODOLOGY: The chemical composition of Portland cement, MTA Angelus, tricalcium
      silicate cement, Biodentine and Bioaggregate was determined using X-ray
      fluorescence (XRF). Measurements of arsenic, lead and chromium were taken with
      inductively coupled plasma-mass spectrometry (ICP-MS), following acid digestion
      on the hydrated material and on leachates of cements soaked in Hank's balanced
      salt solution (HBSS). RESULTS: All the cements investigated had a similar oxide
      composition with the main oxide being calcium and silicon oxide. Both the
      Portland cement and MTA Angelus had an additional aluminium oxide. The dental
      cements included a radiopacifying material. All the materials tested had higher
      acid-extractable arsenic content than the level set by ISO 9917-1 (2007) and an
      acceptable level of lead. Regardless these high levels of trace elements present
      in the materials, the leaching in HBSS was minimal for all the dental material
      tested in contrast to the high levels displayed by Portland cement. CONCLUSIONS:
      Dental materials based on tricalcium silicate cement and MTA Angelus release
      minimal quantities of trace elements when in contact with simulated body fluids.
      The results of acid extraction could be affected by nonspecific matrix effects by
      the cement.

PMID- 22394278
TI  - Clarifying omics concepts, challenges, and opportunities for Prunus breeding in
      the postgenomic era.
AB  - The recent sequencing of the complete genome of the peach, together with the
      availability of new high-throughput genome, transcriptome, proteome, and
      metabolome analysis technologies, offers new possibilities for Prunus breeders in
      what has been described as the postgenomic era. In this context, new biological
      challenges and opportunities for the application of these technologies in the
      development of efficient marker-assisted selection strategies in Prunus breeding
      include genome resequencing using DNA-Seq, the study of RNA regulation at
      transcriptional and posttranscriptional levels using tilling microarray and RNA
      Seq, protein and metabolite identification and annotation, and standardization of
      phenotype evaluation. Additional biological opportunities include the high level
      of synteny among Prunus genomes. Finally, the existence of biases presents
      another important biological challenge in attaining knowledge from these new high
      throughput omics disciplines. On the other hand, from the philosophical point of
      view, we are facing a revolution in the use of new high-throughput analysis
      techniques that may mean a scientific paradigm shift in Prunus genetics and
      genomics theories. The evaluation of scientific progress is another important
      question in this postgenomic context. Finally, the incommensurability of omics
      theories in the new high-throughput analysis context presents an additional
      philosophical challenge.

PMID- 22394279
TI  - Knowledge gaps in risk assessment of nanosilica in food: evaluation of the
      dissolution and toxicity of different forms of silica.
AB  - This manuscript describes the follow-up study of our previous publication on the
      presence and risks of nanosilica in food. New information on the presence of
      nanosilica in the gastrointestinal tract is evaluated and information on
      nanosilica and synthetic amorphous silica (SAS) is compared to assess its
      relevance for risk assessment of nanosilica in food. Irrespective of whether SAS
      should be regarded as a nanomaterial or a non-nanoform of silica, a comparison to
      nanosilica is relevant to determine whether there are differences in
      physicochemical properties, which may lead to differences in toxicity. Based on
      this comparison, knowledge gaps are identified and recommendations for a targeted
      approach to facilitate risk assessment of nanosilica in food are given.
      Considering the discussion to which extent nanomaterials with (slightly)
      different physicochemical characteristics can be grouped for risk assessment--the
      sameness issue--actual exercises as presented in this manuscript are highly
      relevant for bringing this discussion forward.

PMID- 22394280
TI  - Analysis of some reaction pathways active during cyclopentadiene pyrolysis.
AB  - The cyclopentadienyl radical (cC(5)H(5)) is among the most stable radical species
      that can be generated during the combustion and pyrolysis of hydrocarbons and it
      is generally agreed that its contribution to the gas phase reactivity is
      significant. In this study the kinetics of one key cC(5)H(5) reaction channel,
      namely the reaction between cC(5)H(5) and cyclopentadiene (cC(5)H(6)), was
      investigated using ab initio calculations and RRKM/Master Equation theory. It was
      found that most of the excited C(5)H(5)_C(5)H(6) adducts formed by the addition
      of cC(5)H(5) to cC(5)H(6) decompose back to reactants and that the major reaction
      products are, in order of importance, indene, vinylfulvene (a most probable
      styrene precursor), phenylbutadiene, and benzene. The preferred reaction pathway
      of the C(5)H(5)_C(5)H(6) adduct is started by the migration of the tertiary
      hydrogen of the C(5)H(5) ring to a vicinal carbon and followed by the beta
      opening of the C(5)H(6) ring, which is the rate determining step. Successive
      molecular rearrangements lead to decomposition to the four possible products. The
      kinetic constants for the four reaction channels, calculated at atmospheric
      pressure and interpolated in cm(3) mol(-1) s(-1) between 900 and 2000 K, are
      k(indene) = 10(25.197)T(-3.935) exp(-11630/T(K)), k(vinylfulvene) = 10(65.077)T(
      14.20) exp(-37567/T(K)), k(benzene) = 10(29.172)T(-4.515) exp(-20570/T(K)), and
      k(phenylbutadiene) = 10(16.743)T(-1.407) exp(-11804/T(K)). The predictive
      capability of the reaction set so determined was tested through the simulations
      of recent cC(5)H(6) pyrolysis and combustion experiments using a detailed kinetic
      mechanism. A quantitative agreement with experimental data was obtained by
      assuming that vinylfulvene converts rapidly to stryrene, increasing its reaction
      channel by a factor of 2, and assuming that phenylbutadiene rapidly decomposes
      with equal probability to styrene and benzene.

PMID- 22394281
TI  - Pharmacokinetics and topical vaginal effects of two tenofovir gels in rabbits.
AB  - Tenofovir (TFV) 1% gel has proven effective in preclinical and clinical studies
      in preventing sexual transmission of HIV-1. The impact of changing the current
      gel formulation to reduce its osmolality was evaluated using pharmacokinetic
      assessments and local tissue effects in the rabbit. Following vaginal
      administration of TFV 1% gel and reduced-glycerin TFV 1% gel, TFV was measured in
      plasma, vaginal tissues, vaginal fluids, and iliac lymph nodes. After a single
      dose, plasma C(max) and AUC(0-4h) were significantly higher in the TFV 1% gel
      group compared with the reduced-glycerin TFV 1% gel group. After 14 days of once
      daily dosing, differences in these parameters were insignificant. Vaginal fluid
      concentrations were ~100 MUg/ml following the first dose and up to a mean of
      about 500 MUg/ml after 14 once-daily doses. Mean (and median) cranial TFV tissue
      concentrations were generally in excess of 100 MUg/g following a single dose and
      14 once-daily doses of both gels; concentrations in the caudal vaginal tissues
      were comparatively lower, although in nearly all cases mean values exceeded 10
      MUg/g. Treatment of tissues with phosphatase to liberate TFV from its diphosphate
      and monophosphate metabolites increased recovery of TFV by 60-120%. Median TFV
      concentrations in iliac lymph nodes ranged from 44 ng/g to 196 ng/g; differences
      between iliac lymph node TFV concentrations following dosing of the two gels were
      insignificant. There were no differences observed in histological evaluation in
      the cranial vagina following 14 days of once-daily dosing of either gel. There
      was an apparent impact of TFV on rabbit vaginal epithelium (increased secretory
      depletion and increased cellular vacuolization) independent of formulation. These
      data indicate that the reduced-glycerin TFV 1% gel may be a suitable alternative
      to TFV 1% gel.

PMID- 22394282
TI  - Zinc-mediated diastereoselective synthesis of 3-amino oxindoles by addition of
      methyl and terminal alkynes to N-tert-butanesulfinyl ketimines.
AB  - A zinc-mediated addition of methyl and terminal alkynes to chiral N-tert
      butanesulfinyl ketimines for the preparation of optical quaternary 3-amino
      oxindoles was reported. In general, the operationally simple reaction affords the
      desired products in high yields and good to excellent diastereoselectivities.
      Subsequent convenient cleavage of sulfinyl protecting group under mild conditions
      was presented without racemization.

PMID- 22394283
TI  - On the pH-dependent quenching of quantum dot photoluminescence by redox active
      dopamine.
AB  - We investigated the charge transfer interactions between luminescent quantum dots
      (QDs) and redox active dopamine. For this, we used pH-insensitive ZnS-overcoated
      CdSe QDs rendered water-compatible using poly (ethylene glycol)-appended
      dihydrolipoic acid (DHLA-PEG), where a fraction of the ligands was amine
      terminated to allow for controlled coupling of dopamine-isothiocyanate onto the
      nanocrystal. Using this sample configuration, we probed the effects of changing
      the density of dopamine and the buffer pH on the fluorescence properties of these
      conjugates. Using steady-state and time-resolved fluorescence, we measured a
      pronounced pH-dependent photoluminescence (PL) quenching for all QD-dopamine
      assemblies. Several parameters affect the PL loss. First, the quenching
      efficiency strongly depends on the number of dopamines per QD-conjugate. Second,
      the quenching efficiency is substantially increased in alkaline buffers. Third,
      this pH-dependent PL loss can be completely eliminated when oxygen-depleted
      buffers are used, indicating that oxygen plays a crucial role in the redox
      activity of dopamine. We attribute these findings to charge transfer interactions
      between QDs and mainly two forms of dopamine: the reduced catechol and oxidized
      quinone. As the pH of the dispersions is changed from acidic to basic, oxygen
      catalyzed transformation progressively reduces the dopamine potential for
      oxidation and shifts the equilibrium toward increased concentration of quinones.
      Thus, in a conjugate, a QD can simultaneously interact with quinones (electron
      acceptors) and catechols (electron donors), producing pH-dependent PL quenching
      combined with shortening of the exciton lifetime. This also alters the
      recombination kinetics of the electron and hole of photoexcited QDs. Transient
      absorption measurements that probed intraband transitions supported those
      findings where a simultaneous pronounced change in the electron and hole
      relaxation rates was measured when the pH was changed from acidic to alkaline.

PMID- 22394284
TI  - Bad statistical practice in pharmacology (and other basic biomedical
      disciplines): you probably don't know P.
AB  - Statistical analysis is universally used in the interpretation of the results of
      basic biomedical research, being expected by referees and readers alike. Its role
      in helping researchers to make reliable inference from their work and its
      contribution to the scientific process cannot be doubted, but can be improved.
      There is a widespread and pervasive misunderstanding of P-values that limits
      their utility as a guide to inference, and a change in the manner in which P
      values are specified and interpreted will lead to improved outcomes. This paper
      explains the distinction between Fisher's P-values, which are local indices of
      evidence against the null hypothesis in the results of a particular experiment,
      and Neyman-Pearson alpha levels, which are global rates of false positive errors
      from unrelated experiments taken as an aggregate. The vast majority of papers
      published in pharmacological journals specify P-values, either as exact-values or
      as being less than a value (usually 0.05), but they are interpreted in a hybrid
      manner that detracts from their Fisherian role as indices of evidence without
      gaining the control of false positive and false negative error rate offered by a
      strict Neyman-Pearson approach. An informed choice between those approaches
      offers substantial advantages to the users of statistical tests over the current
      accidental hybrid approach.

PMID- 22394285
TI  - Lung transplantation in the fischer 344-wistar kyoto strain combination is a
      relevant experimental model to study the development of bronchiolitis obliterans
      in the rat.
AB  - Chronic allograft rejection and bronchiolitis obliterans (BO) limited successful
      long-term outcome after lung transplantation (LTX). Reliable animal models are
      needed to study the pathogenesis of BO and to develop effective therapeutic
      strategies. The relevance of an available experimental LTX model without
      immunosuppression-the Fischer (F344)-Wistar Kyoto (WKY) rat strain combination
      was analyzed. The kinetics of acute and chronic rejection and respective graft
      histopathology were described in the F344-to-WKY rat strain combination after
      allogeneic LTX. A modified classification of chronic lung allograft rejection was
      introduced to describe obliterative changes in the airways after rat LTX. Animals
      from Harlan Winkelmann (HW) and Charles River (CR) were examined. Within 14 days
      after LTX, allografts showed moderate to severe acute vascular and bronchiolar
      inflammation. In contrast to rats from CR, animals from HW showed a delayed acute
      rejection process. Mid-term phase after LTX (days 20-40) presented a "borderline
      form" consisting of both acute and first signs of chronic airway rejection. On
      postoperative day (POD) 60, first signs of airway remodelling and distinct BO
      were diagnosed in 80% of animals from HW. At the same time, the allografts with
      BO-like lesions increased up to 100% in rats from CR. The F344-to-WKY rat LTX
      model allows detailed assessment of all features of acute and chronic pulmonary
      rejection representing a clinically relevant model. However, due to breeding
      differences resulting in various sublines of the same rat strain, the source and
      husbandary history of the animals is important for analysis of immuno-mediated
      processes.

PMID- 22394286
TI  - Telomerase deficiency does not alter bleomycin-induced fibrosis in mice.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by interstitial lung
      infiltrates, dyspnea, and progressive respiratory failure. Reports linking
      telomerase mutations to familial interstitial pneumonia (FIP) suggest that
      telomerase activity and telomere length maintenance are important in disease
      pathogenesis. To investigate the role of telomerase in lung fibrotic remodeling,
      intratracheal bleomycin was administered to mice deficient in telomerase reverse
      transcriptase (TERT) or telomerase RNA component (TERC) and to wild-type
      controls. TERT-deficient and TERC-deficient mice were interbred to the F6 and F4
      generation, respectively, when they developed skin manifestations and
      infertility. Fibrosis was scored using a semiquantitative scale and total lung
      collagen was measured using a hydroxyprolinemicroplate assay. Telomere lengths
      were measured in peripheral blood leukocytes and isolated type II alveolar
      epithelial cells (AECs). Telomerase activity in type II AECs was measured using a
      real-time polymerase chain reaction (PCR)-based system. Following bleomycin, TERT
      deficient and TERC-deficient mice developed an equivalent inflammatory response
      and similar lung fibrosis (by scoring of lung sections and total lung collagen
      content) compared to controls, a pattern seen in both early (F1) and later (F6
      TERT and F4 TERC) generations. Telomere lengths were reduced in peripheral blood
      leukocytes and isolated type II AECs from F6 TERT-deficient and F4 TERC-deficient
      mice compared to controls. Telomerase deficiency in a murine model leads to
      telomere shortening, but does not predispose to enhanced bleomycin-induced lung
      fibrosis. Additional genetic or environmental factors may be necessary for
      development of fibrosis in the presence of telomerase deficiency.

PMID- 22394288
TI  - Infliximab attenuates activated charcoal and polyethylene glycol aspiration
      induced lung injury in rats.
AB  - Aspiration is a serious complication of gastrointestinal (GI) decontamination
      procedure. Studies have shown that tumor necrosis factor-alpha (TNF-alpha)
      blockers have beneficial effects on lung injury. Therefore, the authors
      investigated the attenuation by infliximab (INF) on activated charcoal (AC)- and
      polyethylene glycol (PEG)-induced lung injury in rat model. Forty-two male
      Sprague-Dawley rats were allotted into 1 of 6 groups: saline (NS), activated
      charcoal (AC), polyethylene glycol (PEG), NS+INF treated, AC+INF treated, and
      PEG+INF treated. All materials were aspirated into the lungs at a volume of 1
      mL/kg. Before aspiration, the rats were injected subcutaneously with INF. Seven
      days later, both lungs and serum specimens in all groups were evaluated
      histopathologically, immunohistochemically, and biochemically. Following
      aspiration of AC and PEG, evident histopathological changes were assigned in the
      lung tissue that were associated with increased expression of inducible nitric
      oxide synthase (iNOS), increased serum levels of oxidative stress markers
      (malondialdehyde [MDA], surfactant protein-D [SP-D], TNF-alpha), and decreased
      antioxidant enzyme (glutathione peroxidase [GSH-Px]) activities. INF treatment
      significantly decreased the elevated serum MDA and TNF-alpha levels and increased
      serum GSH-Px levels. Furthermore, the current results show that there is a
      significant reduction in the activity of iNOS in lung tissue and increased serum
      SP-D levels of AC and PEG aspiration-induced lung injury with INF treatment.
      These findings suggest that INF attenuates lung inflammation and prevents GI
      decontamination agent-induced lung injury in rats.

PMID- 22394289
TI  - Time course of the inflammatory and oxidative stress response to pulmonary
      infection in mice.
AB  - The pathophysiological response to pulmonary infection includes a surge of
      proinflammatory cytokines and excessive production of nitric oxide (NO), but the
      time changes are not sufficiently defined. The current study was designed to
      assess the time course of proinflammatory cytokines and NO production in a murine
      model of pulmonary infection. The injury was induced by intranasal administration
      of live Pseudomonas aeruginosa (3.2 * 10(7) colony-forming units) in C57BL/6 wild
      type mice. The animals were euthanized at 3, 6, 9, 12, and 15 hours postinjury.
      Additional mice received sham injury (0 hours; control). Lung tissue and plasma
      samples were harvested at the respective time points. The injury induced an early
      increase in interleukin (IL)-1 beta protein in lung tissue that persisted during
      the entire study period with a peak at the 9-hour time point. The increases in
      TNF-alpha and IL-6 proteins in lung tissue were less intense, but showed a peak
      about 9 hours postinjury. The plasma levels of IL-1 beta and tumor necrosis
      factor (TNF)-alpha protein were not elevated during the experimental period, but
      only an increase in plasma levels of IL-6 plasma protein was detected. These
      findings compensate for the limitations of previous experiments with similar
      infection models and improve the understanding of pathophysiologic alterations in
      response to pulmonary infection. In addition, the identification of the time
      changes of the described pathogenetic factors may enhance the timing of innovate
      therapeutic approaches in future experiments.

PMID- 22394287
TI  - Intratracheal bleomycin causes airway remodeling and airflow obstruction in mice.
AB  - In addition to parenchymal fibrosis, fibrotic remodeling of the distal airways
      has been reported in interstitial lung diseases. Mechanisms of airway wall
      remodeling, which occurs in a variety of chronic lung diseases, are not well
      defined and current animal models are limited. The authors quantified airway
      remodeling in lung sections from subjects with idiopathic pulmonary fibrosis
      (IPF) and controls. To investigate intratracheal bleomycin as a potential animal
      model for fibrotic airway remodeling, the authors evaluated lungs from C57BL/6
      mice after bleomycin treatment by histologic scoring for fibrosis and
      peribronchial inflammation, morphometric evaluation of subepithelial connective
      tissue volume density, TUNEL (terminal deoxynucleotidyl transferase dUTP-mediated
      nick-end labeling) assay, and immunohistochemistry for transforming growth factor
      beta1 (TGFbeta1), TGFbeta2, and the fibroblast marker S100A4. Lung mechanics were
      determined at 3 weeks post bleomycin. IPF lungs had small airway remodeling with
      increased bronchial wall thickness compared to controls. Similarly, bleomycin
      treated mice developed dose-dependent airway wall inflammation and fibrosis and
      greater airflow resistance after high-dose bleomycin. Increased TUNEL(+)
      bronchial epithelial cells and peribronchial inflammation were noted by 1 week,
      and expression of TGFbeta1 and TGFbeta2 and accumulation of S100A4(+) fibroblasts
      correlated with airway remodeling in a bleomycin dose-dependent fashion. IPF is
      characterized by small airway remodeling in addition to parenchymal fibrosis, a
      pattern also seen with intratracheal bleomycin. Bronchial remodeling from
      intratracheal bleomycin follows a cascade of events including epithelial cell
      injury, airway inflammation, profibrotic cytokine expression, fibroblast
      accumulation, and peribronchial fibrosis. Thus, this model can be utilized to
      investigate mechanisms of airway remodeling.

PMID- 22394290
TI  - Promotion of evidence-informed health policymaking in Nigeria: bridging the gap
      between researchers and policymakers.
AB  - In Nigeria, the lack of adequate understanding of the complex nature of
      translating research into policy and the incompatibility existing between
      researchers and policymakers constitute a great challenge to evidence-informed
      policymaking. To address these challenges a one-day evidence-to-policy training
      workshop was organised for policymakers, researchers and other major stakeholders
      in the health sector in southeastern Nigeria. Of the 104 individuals invited to
      the workshop 87 (83.6%) attended. The workshop training sessions focused on
      capacity development for evidence-informed health policy-making and building
      effective linkages/partnerships. The post-workshop assessment indicated
      significant improvements in participants' knowledge, their understanding of the
      health policymaking process and the use of evidence compared to their pre
      workshop status. Using a focus group discussion, major strategies identified by
      participants that can bridge the gap between health policymakers and researchers
      included: involving both parties in planning and execution of health research and
      health programmes; promoting dialogue between researchers and policymakers;
      institutionalising research grants and commissioning research in health
      ministries; and ensuring that researchers are made to focus on the core needs of
      policymakers. There is need for further discussion and debate on the researchers
      and policymakers partnership concept in low income settings.

PMID- 22394291
TI  - Review: Creutzfeldt-Jakob disease: prion protein type, disease phenotype and
      agent strain.
AB  - The human transmissible spongiform encephalopathies or human prion diseases are
      one of the most intensively investigated groups of rare human neurodegenerative
      conditions. They are generally held to be unique in terms of their complex
      epidemiology and phenotypic variability, but they may also serve as a paradigm
      with which other more common protein misfolding disorders might be compared and
      contrasted. The clinico-pathological phenotype of human prion diseases appears to
      depend on a complex interaction between the prion protein genotype of the
      affected individual and the physico-chemical properties of the neurotoxic and
      transmissible agent, thought to comprise of misfolded prion protein. A major
      focus of research in recent years has been to define the phenotypic heterogeneity
      of the recognized human prion diseases, correlate this with molecular-genetic
      features and then determine whether this molecular-genetic classification of
      human prion disease defines the biological properties of the agent as determined
      by animal transmission studies. This review seeks to survey the field as it
      currently stands, summarize what has been learned, and explore what remains to be
      investigated in order to obtain a more complete scientific understanding of prion
      diseases and to protect public health.

PMID- 22394292
TI  - Is aggressive treatment of traumatic brain injury cost-effective?
AB  - OBJECT: The object of this study was to determine whether aggressive treatment of
      severe traumatic brain injury (TBI), including invasive intracranial monitoring
      and decompressive craniectomy, is cost-effective. METHODS: A decision-analytical
      model was created to compare costs, outcomes, and cost-effectiveness of 3
      strategies for treating a patient with severe TBI. The aggressive-care approach
      is compared with "routine care," in which Brain Trauma Foundation guidelines are
      not followed. A "comfort care" category, in which a single day in the ICU is
      followed by routine floor care, is included for comparison only. Probabilities of
      each treatment resulting in various Glasgow Outcome Scale (GOS) scores were
      obtained from the literature. The GOS scores were converted to quality-adjusted
      life years (QALYs), based on expected longevity and calculated quality of life
      associated with each GOS category. Estimated direct (acute and long-term medical
      care) and indirect (loss of productivity) costs were calculated from the
      perspective of society. Sensitivity analyses employed a 2D Monte Carlo simulation
      of 1000 trials, each with 1000 patients. The model was also used to estimate
      these values for patients 40, 60, and 80 years of age. RESULTS: For the average
      20-year-old, aggressive care yields 11.7 (+/- 1.6 [SD]) QALYs, compared with
      routine care (10.0 +/- 1.5 QALYs). This difference is highly significant (p <
      0.0001). Although the differences in effectiveness between the 2 strategies
      diminish with advancing age, aggressive care remains significantly better at all
      ages. When all costs are considered, aggressive care is also significantly less
      costly than routine care ($1,264,000 +/- $118,000 vs $1,361,000 +/- $107,000) for
      the average 20-year-old. Aggressive care remains significantly less costly until
      age 80, at which age it costs more than routine care. However, even in the 80
      year-old, aggressive care is likely the more cost-effective approach. Comfort
      care is associated with poorer outcomes at all ages and with higher costs for all
      groups except 80-year-olds. CONCLUSIONS: When all the costs of severe TBI are
      considered, aggressive treatment is a cost-effective option, even for older
      patients. Comfort care for severe TBI is associated with poor outcomes and high
      costs, and should be reserved for situations in which aggressive approaches have
      failed or testing suggests such treatment is futile.

PMID- 22394293
TI  - Neurosurgical complications of direct thrombin inhibitors--catastrophic
      hemorrhage after mild traumatic brain injury in a patient receiving dabigatran.
AB  - Dabigatran etexilate is an oral anticoagulant that acts as a direct, competitive
      thrombin inhibitor. Large randomized clinical trials have shown higher doses of
      dabigatran (150 mg taken twice daily) to be superior to warfarin in terms of
      stroke and systemic embolism rates in patients with nonvalvular atrial
      fibrillation. As a result, in 2010 the US FDA approved the use of dabigatran for
      the prevention of stroke and systemic embolism in patients with atrial
      fibrillation. Dabigatran is especially attractive in the outpatient setting
      because patients do not require routine monitoring with prothrombin times or
      international normalized ratios. To date, no effective reversal agent for
      dabigatran in the event of catastrophic hemorrhage has been identified. The
      authors report a case of an elderly patient, being treated with dabigatran for
      atrial fibrillation, who presented with a rapidly expanding intracranial
      hemorrhage after a ground-level fall. This case highlights an impending
      neurosurgical quandary of complications secondary to this new anticoagulation
      agent and suggests potential options for management.

PMID- 22394294
TI  - Focal nodular hyperplasia precedes hepatocellular carcinoma in an adult with
      congenital absence of the portal vein.

PMID- 22394295
TI  - A new evaluation of the upper esophageal sphincter using the functional lumen
      imaging probe: a preliminary report.
AB  - Objective and reliable evaluation of upper esophageal sphincter (UES) opening
      during swallowing based on videofluoroscopy and pharyngeal manometry challenges
      dysphagia clinicians. The functional lumen imaging probe (FLIP) is a portable
      tool based on impedance planimetry originally designed to measure esophogastric
      junction compliance. It is hypothesized that FLIP can evaluate UES
      distensibility, and can provide UES diameter and pressure measurements at rest,
      during swallowing, and during voluntary maneuvers. Eleven healthy adult subjects
      consented to FLIP evaluation. The probe was inserted transorally, and the balloon
      was positioned across the UES. Two 20-mL ramp distensions were completed. Changes
      in UES diameter and intraballoon pressure were measured during dry and 5-mL
      liquid swallows, and during voluntary swallow postures and maneuvers employed in
      clinical practice. The protocol was completed by 10 of 11 healthy subjects. Mean
      intraballoon pressure increased throughout 5-mL (5.8 mmHg; -4.5-18.6 mmHg), 10-mL
      (8.7 mmHg; 2.3-28.5 mmHg), 15-mL (17.3 mmHg; 9.5-34.8 mmHg), and 20-mL (31.2
      mmHg; 16-46.3 mmHg) balloon volumes. Mean resting UES diameter (4.9 mm) increased
      during dry swallows (9.2 mm) and 5-mL liquid swallows (7.7 mm). Mean UES diameter
      increased during 5-mL liquid swallows with head turn to right (8.1 mm) and left
      (8.3 mm), chin tuck (8.4 mm), effortful swallow (8.5 mm), Mendelsohn maneuver
      (8.1 mm), and supraglottic swallow (7.8 mm). FLIP was safely inserted and
      distended in the UES, and provided useful quantitative data regarding UES
      distensibility and UES diameter changes during swallowing maneuvers. Further
      research is being conducted to explore the role of FLIP in UES evaluation.

PMID- 22394296
TI  - Reduction of patulin in aqueous solution by lactic acid bacteria.
AB  - This study aims to investigate the ability of lactic acid bacteria (LAB) to
      remove patulin (PAT) from aqueous solution with respect to the bacterial
      viability, initial PAT concentration, incubation time, temperature, and pH. The
      removal of PAT determined by high-performance liquid chromatography (HPLC)
      coupled with UV detector. The maximum PAT uptake was achieved by Bifidobacterium
      bifidum 6071 and Lactobacillus rhamnosus 6149 strains (52.9% and 51.1%) for
      viable and (54.1% and 52.0%) for nonviable cells after 24 h incubation. The
      highest removal of PAT was at pH 4.0 and 37  degrees C and increased with
      decreasing of toxin levels. The removal ability of selected strains could
      represent new strategies for a possible application in contaminated food products
      and animal feed.

PMID- 22394297
TI  - Sex steroids and their receptors: molecular actions on brain cells.
AB  - Sex steroids exert actions of paramount importance on brain cells. They
      contribute to shape the central nervous system during embryo development. They
      modulate the formation and the turnover of the interconnections between neurons.
      They control the function of glial cells. And they do it through a signaling
      machinery that is apparently simple, but that hides a level of complexity that
      has been unveiled only in part. Different receptor isoforms, different
      interactions between receptors and co-regulators, chains of events originating at
      the cell membrane and leading to effects in the nucleus (or the other way around)
      all interact to determine selective modulations of brain cells. All these actions
      end up in phenomenal effects on brain function that change through adolescence,
      pregnancy, adulthood, up to menopause and ageing. Many of these actions are
      relevant for degenerative processes and research may offer soon new strategies to
      counteract these diseases.

PMID- 22394298
TI  - How we almost discovered LH receptors, but didn't.
AB  - The metabolism of gonadotropins was unclear until the 1960s. The chief theory,
      utilization of gonadotropins by gonads, was unproven, but radioimmunoassay
      indicated that the levels of luteinizing hormone entering the ovary were higher
      than the levels in the ovarian veins. The availability of radiolabeled proteins
      opened the possibility of following the fate of gonadotropins in the end organ.
      Independently, two teams in Tel Aviv and Seattle researched the uptake of
      radiolabeled human chorionic gonadotropin by rodent ovary. Both concluded that
      the ovary bound gonadotropin; however, neither pursued the mechanism of the
      observation, gonadotropin receptors on ovarian cells. Had they done so, the
      course of discovery and study of cell surface receptors might have been altered.

PMID- 22394299
TI  - Agonist or antagonist: what is preferable for in vitro fertilization?

PMID- 22394300
TI  - Neuroendocrine aspects of placenta and pregnancy.
AB  - Placenta plays a central role in the regulation of physiological mechanisms of
      pregnancy, and in particular is the organ of communication between mother and
      fetus. This action is also related to its ability to produce hormones, growth
      factors and cytokines during the progression of pregnancy, and in response to
      stimuli such as stress and inflammation/infection. In the last years the
      understanding of the physiological and pathological functions of human placenta
      revealed the hypersecretion of hormones in presence of gestational diseases and
      raised the question whether this mechanism is cause of disorders of pregnancy, or
      part of an adaptive response of placenta to resolve adverse conditions. However,
      there are evidences indicating that changes of placental hormone secretion may
      have clinical usefulness, since they are measurable in biological fluids, and may
      be used as predictive markers or prognostic tools. Of particular interest is the
      role of corticotropin releasing hormone, urocortins and activins in the
      maintaining physiological pregnancy and in the pathogenesis of diseases (preterm
      birth and preeclampsia).

PMID- 22394301
TI  - Neuroendocrine control of metabolism.
AB  - Metabolism is controlled through homeostatic system consisting of central
      centers, gut hormones, hormones from adipose tissue and the other hormonal axes.
      This cooperation is based on cross-talk between central and peripheral signals.
      Among them the hypothalamus plays a crucial role, with interconnected nuclei
      forming neuronal circuits. Other regions in the brain, such as the brain stem,
      the endocannabinoid system, the vagal afferents, are also involved in energy
      balance. The second component is peripheral source of signals--the
      gastrointestinal tract hormones. Additionally, adipokines from adipose tissue,
      thyrotropic, gonadotropic and somatotropic axes play a role in energy
      homeostasis. Knowledge about all components of this neuroendocrine circuit will
      be helpful in developing novel therapeutic approaches against the metabolic
      syndrome and its components.

PMID- 22394302
TI  - Neuroendocrine aspects of migraine in women.
AB  - Migraine is a complex disabling disease influenced mainly by age and gender
      during the life span. Neuroendocrine events related to reproductive stages and to
      the menstrual cycle may cause significant change in the clinical pattern of
      migraine over time, as a consequence of failure in adaptation higher in women
      than in men. Indeed, the individual threshold of vulnerability to manifest
      migraine is modulated by hormonal fluctuations naturally occurring throughout the
      menstrual cycle and at the time of reproductive transitions. In the present short
      review, the role of endogenous estrogen at the level of brain circuitries which
      are involved in multiple cellular, neurochemical and neurophysiological processes
      associated with migraine will be summarized in the context of reproductive
      milestones. In addition, some clues to recognize hormonally sensitive women on
      the basis of their migraine history, i.e. onset, association with menstruation or
      premenstrual syndrome, course during pregnancy and menopause, will be discussed
      in order to expand the knowledge of reproductive endocrinology in the management
      of migraine in women.

PMID- 22394303
TI  - Reproductive depression.
AB  - Reproductive depression is the depression in women that is related to the
      hormonal changes of the menstrual cycle, pregnancy and the menopause and is
      manifested clinically as premenstrual depression, postnatal depression and
      climacteric depression. These three components occur in the same vulnerable women
      in that a woman with depression in the menopausal transition will usually have a
      history of premenstrual syndrome (PMS; premenstrual dysphoric disorder [PMDD]),
      would have been in a good mood during pregnancy and then develop postnatal
      depression. When the periods return the depression becomes cyclical as PMS. These
      three conditions are effectively treated with transdermal estrogens which should
      be the first-choice therapy rather than antidepressants. Estrogens can be used
      together with antidepressants. The critical time to prevent long-term mood
      problems is the correct treatment of postnatal depression. In women with low
      energy and libido, often a side effect of antidepressants, the addition of
      transdermal testosterone is useful. These women with reproductive depression are
      often progesterone/progestogen intolerant and a smaller dose or duration of
      progestogen is a necessary compromise. Alternatively a Mirena IUS or rarely a
      hysterectomy is required.

PMID- 22394304
TI  - Androgens and breast cancer risk.
AB  - Transdermal testosterone supplementation is a treatment option for postmenopausal
      women with distressful decreased libido. Side effects are minor, but there is a
      long-term safety concern with respect to breast cancer, as women with high
      testosterone serum levels appear to be at a significantly increased risk to have
      or to develop breast cancer within a few years. Epidemiological studies of
      sufficient duration to study long-term effects of testosterone supplementation
      are limited, both in number and in methodological quality and are, therefore,
      inconclusive. Preclinical studies do not provide evidence for an androgen
      receptor-mediated stimulating effect of androgens on breast epithelium. However,
      one biologically plausible possibility, which cannot be ruled out, is that
      exogenous androgens become mitogenic after aromatization into bioactive
      oestradiol, either in peripheral fat or within the breast or even within small
      occult tumours. The evidence available so far makes counselling women interested
      in testosterone supplementation for distressful low sexual desire, more of an art
      than science.

PMID- 22394305
TI  - Is H5N1 really highly lethal?
AB  - Medicine for Policymakers is a Journal column that provides decision makers with
      brief explanations of the meaning and implications for biosecurity of clinical
      issues. The articles describe, for a nonmedical audience, hospital practices,
      medical challenges, healthcare delivery issues, and other topics of current
      interest. Readers may submit ideas to the column's editor, Amesh A. Adalja, MD,
      through the Journal's editorial office at  jfox@upmc-biosecurity.org .

PMID- 22394306
TI  - Exploration of 3D activity cliffs on the basis of compound binding modes and
      comparison of 2D and 3D cliffs.
AB  - Activity cliffs are formed by pairs or groups of structurally similar compounds
      having large differences in potency and are focal points of structure-activity
      relationship (SAR) analysis. The choice of molecular representations is a
      critically important aspect of activity cliffs analysis. Thus far, activity
      cliffs have predominantly been defined on the basis of molecular graph or
      fingerprint representations. Herein we introduce 3D activity cliffs derived from
      comparisons of experimentally determined compound binding modes. The analysis of
      3D activity cliffs is generally applicable to target proteins for which
      structures of multiple ligand complexes are available. For two popular targets,
      beta-secretase 1 (BACE1) and factor Xa (FXa), public domain X-ray structures with
      bound inhibitors were collected. Crystallographic binding modes of inhibitors
      were systematically compared using a 3D similarity method taking conformational,
      positional, and atomic property differences into account. In addition, standard
      2D similarity relationships were also determined. SAR information associated with
      individual compounds substantially changed when either bioactive conformations or
      2D molecular graphs were used for similarity evaluation. 3D activity cliffs were
      identified for BACE1 and FXa inhibitor sets and systematically compared to 2D
      cliffs. It was found that less than 40% of 3D activity cliffs were conserved when
      2D similarity was applied. The limited conservation of 3D and 2D cliffs provides
      further evidence for the strong molecule representation dependence of activity
      cliffs. Moreover, 3D cliffs represent a new class of activity cliffs that convey
      SAR information in ways that differ from graph-based similarity measures. In
      cases where sufficient structural information is available, the comparison of 3D
      and 2D cliffs is expected to aid in SAR analysis and mapping of critical binding
      determinants.

PMID- 22394307
TI  - Hot electron field emission via individually transistor-ballasted carbon nanotube
      arrays.
AB  - We present electronically controlled field emission characteristics of arrays of
      individually ballasted carbon nanotubes synthesized by plasma-enhanced chemical
      vapor deposition on silicon-on-insulator substrates. By adjusting the source
      drain potential we have demonstrated the ability to controllable limit the
      emission current density by more than 1 order of magnitude. Dynamic control over
      both the turn-on electric field and field enhancement factor have been noted. A
      hot electron model is presented. The ballasted nanotubes are populated with hot
      electrons due to the highly crystalline Si channel and the high local electric
      field at the nanotube base. This positively shifts the Fermi level and results in
      a broad energy distribution about this mean, compared to the narrow spread, lower
      energy thermalized electron population in standard metallic emitters. The
      proposed vertically aligned carbon nanotube field-emitting electron source offers
      a viable platform for X-ray emitters and displays applications that require
      accurate and highly stable control over the emission characteristics.

PMID- 22394308
TI  - Asymmetric hydrovinylation of vinylindoles. A facile route to cyclopenta[g]indole
      natural products (+)-cis-trikentrin A and (+)-cis-trikentrin B.
AB  - Vinylindoles undergo Ni(II)-catalyzed asymmetric hydrovinylation under very mild
      conditions (-78  degrees C, 1 atm ethylene, 4 mol % catalyst) to give the
      corresponding 2-but-3-enyl derivatives in excellent yields and
      enantioselectivities. Hydroboration of the alkene and oxidation to an acid,
      followed by Friedel-Crafts annulation, gives an indole-annulated cyclopentanone
      that is a suitable precursor for the syntheses of cis-trikentrins and all known
      herbindoles. For example, the cyclopentanone from 4-ethyl-7-vinylindole is
      converted into (+)-cis-trikentin A in four steps (Wittig reaction, alkene
      isomerization, diastereoselective hydrogenation, and nitrogen deprotection). The
      previous synthesis of this molecule from (S)-(-)-malic acid involved more than 20
      steps and a preparative HPLC separation of diastereomeric intermediates.

PMID- 22394309
TI  - Highly stereoselective chemoenzymatic synthesis of the 3H-isobenzofuran skeleton.
      Access to enantiopure 3-methylphthalides.
AB  - A straightforward synthesis of (S)-3-methylphthalides has been developed, with
      the key asymmetric step being the bioreduction of 2-acetylbenzonitriles.
      Enzymatic processes have been found to be highly dependent on the pH value, with
      acidic conditions being required to avoid undesired side reactions. Baker's yeast
      was found to be the best biocatalyst acting in a highly stereoselective fashion.
      The simple treatment of the reaction crudes with aqueous HCl has provided access
      to enantiopure (S)-3-methylphthalides in moderate to excellent yields.

PMID- 22394310
TI  - In vitro mechanistic study towards a better understanding of ZnO nanoparticle
      toxicity.
AB  - ZnO nanoparticles (NPs) elicit significant adverse effects in various cell types,
      organisms and in the environment. The toxicity of nanoscale ZnO has often been
      ascribed to the release of zinc ions from the NPs but it is not yet understood to
      which extent these ions contribute to ZnO NP toxicity and what are the underlying
      mechanisms. Here, we take one step forward by demonstrating that ZnO-induced
      Jurkat cell death is largely an ionic effect involving the extracellular release
      of high amounts of Zn(II), their rapid uptake by the cells and the induction of a
      caspase-independent alternative apoptosis pathway that is independent of the
      formation of ROS. In addition, we identified novel coating strategies to reduce
      ZnO NP dissolution and subsequent adverse effects.

PMID- 22394311
TI  - Endodontic management of mandibular central incisor fused to a supernumerary
      tooth associated with a talon cusp: a case report.
AB  - AIM: To report the successful non-surgical endodontic management of a mandibular
      central incisor fused to a supernumerary tooth associated with a talon cusp.
      SUMMARY: Fusion and gemination are developmental anomalies of teeth that may
      require endodontic treatment. In this article, a case of successful endodontic
      management of a permanent mandibular right central incisor fused to its
      supernumerary counterpart associated with a talon cusp is reported. The incidence
      of fusion in mandibular anteriors is rare. A search of the literature failed to
      reveal any reports on the fusion of a permanent mandibular central incisor with
      its supernumerary counterpart associated with a talon cusp. Successful non
      surgical endodontic management of a case is reported. KEY LEARNING POINTS: * 
      Fused and geminated teeth requiring endodontic treatment present diagnostic and
      technical challenges. * An exact differentiation between fusion and gemination
      may not be critically important for treatment. * The use of an operating
      microscope for detection of additional root canal orifices in complicated cases
      is recommended.

PMID- 22394312
TI  - Quantification of local hydration at the surface of biomolecules using dual
      fluorescence labels.
AB  - By using four labels of the 3-hydroxyflavone family displaying selective
      sensitivity to hydrogen bond (HB) donors and poor response to other polar
      molecules, we developed an approach for measuring local water concentration
      [H(2)O](L) (or partial volume of water: W(A) = [H(2)O](L)/55.6) in the label
      surrounding both in solvent mixtures and in biomolecules by the intensity ratio
      of two emissive forms of the label, N*/T*. Using a series of binary water/solvent
      mixtures with limited preferential solvation effects, a linear dependence of
      log(N*/T*) on the local concentration of HB donor was obtained and then used as a
      calibration curve for estimating the W(A) values in the surroundings of the
      probes conjugated to biomolecules. By this approach, we estimated the hydration
      of the labels in different peptides and their complexes with DNAs. We found that
      W(A) values for the label at the peptide N-terminus are lower (0.63-0.91) than
      for free labels and depend strongly on the nature of the N-terminal amino acid.
      When complexed with different DNAs, the estimated hydration of the labels
      conjugated to the labeled peptides was much lower (W(A) = 0-0.47) and depended on
      the DNA nature and linker-label structure. Thus, the elaborated method allows a
      site-specific evaluation of hydration at the surface of a biomolecule through the
      determination of the partial volume of water. We believe the developed procedure
      can be successfully applied for monitoring hydration at the surface of any
      biomolecule or nanostructure.

PMID- 22394313
TI  - Smoking during pregnancy: lessons learned from epidemiological studies and
      experimental studies using animal models.
AB  - Numerous epidemiological studies in the human population clearly indicate that
      smoking while pregnant has deleterious effects on fetal development as well as
      long-term adverse consequences on postnatal development and maturation of several
      organ systems. Low birth weight, sudden infant death syndrome (SIDS), behavioral
      disorders including attention deficit hyperactivity disorder (ADHD),
      externalizing and internalizing behavioral problems and conduct disorders in
      children have all been linked to prenatal exposure to tobacco smoke. The major
      pharmacologically active chemical found in tobacco smoke is nicotine, and
      prenatal exposure to nicotine has been shown to have significant effect on the
      development of multiple organ systems, including the nervous, respiratory, and
      cardiovascular systems. In this review, we define mainstream and sidestream
      smoke, summarize the major classes of compounds found in cigarette smoke, and
      describe how use of laboratory animal models can be used to assess mechanisms of
      toxicity and risk in the human population in general. We then discuss the
      association with smoking during pregnancy and the occurrence of reduced lung
      function, low birth weight, the incidence of congenital structural malformations,
      SIDS, ADHD, cognitive impairment, and mood disorders in children, and review
      pertinent experimental studies using a variety of animal models of developmental
      nicotine exposure, including, rats, mice, monkeys, lambs, and pigs that have
      increased our understanding of the pathophysiology of these disorders.

PMID- 22394315
TI  - A population pharmacokinetic-pharmacogenetic analysis of atazanavir.
AB  - Atazanavir is a first-line HIV protease inhibitor commonly co-dosed with
      ritonavir. Ritonavir inhibits atazanavir metabolism, decreasing variability and
      increasing plasma concentrations. However, ritonavir use results in higher costs
      and increased drug-related adverse events. Elucidating atazanavir
      pharmacokinetics might allow for individualized ritonavir boosting. We previously
      demonstrated that genetically determined CYP3A5 nonexpression was associated with
      slower atazanavir clearance CL/F and higher trough concentrations. This effect
      was prominent in non-African-American men but absent in African-Americans. The
      present study considers additional genetic predictors of atazanavir CL/F with a
      focus on race differences. Nine polymorphisms in CYP3A4, ABCG2, NR1I2 (PXR), and
      SLCO1B1 were evaluated; 330 plasma samples from 30 HIV-negative volunteers,
      balanced by sex, race, and CYP3A5 expressor status, were available. Analyses were
      performed using nonlinear mixed-effects modeling (NONMEM). The following factors
      were univariately associated with atazanavir CL/F (% effect) : African-American
      race (decreased 35%), female sex (decreased 25%), older age (decreased
      1.7%/year), CYP3A5 nonexpressors (decreased 26%), ABCB1 CGC haplotype carriers
      (1236C/2677G/3435C) (decreased 33%), and CYP3A4*1B carriers (decreased 31%).
      However, an independent genetic explanation for the differential race effect
      could not be identified. An interaction was observed with PXR 63396 C>T and
      CYP3A5 expressor status (p=0.0002). CYP3A5 nonexpressors with a PXR 63396 CC
      genotype had 37% slower CL/F versus those with CT or TT genotypes. For CYP3A5
      expressors, those with a PXR 63396 CC genotype had 63% faster CL/F versus those
      with CT or TT genotypes. Although this study has as its main limitation a small
      overall sample size, these results nonetheless provide new leads and impetus to
      evaluate ways to individualize the need for ritonavir boosting using demographic
      and genetic predictors of atazanavir pharmacokinetics.

PMID- 22394314
TI  - The orphan histidine protein kinase SgmT is a c-di-GMP receptor and regulates
      composition of the extracellular matrix together with the orphan DNA binding
      response regulator DigR in Myxococcus xanthus.
AB  - In Myxococcus xanthus the extracellular matrix is essential for type IV pili
      dependent motility and starvation-induced fruiting body formation. Proteins of
      two-component systems including the orphan DNA binding response regulator DigR
      are essential in regulating the composition of the extracellular matrix. We
      identify the orphan hybrid histidine kinase SgmT as the partner kinase of DigR.
      In addition to kinase and receiver domains, SgmT consists of an N-terminal GAF
      domain and a C-terminal GGDEF domain. The GAF domain is the primary sensor
      domain. The GGDEF domain binds the second messenger bis-(3'-5')-cyclic-dimeric
      GMP (c-di-GMP) and functions as a c-di-GMP receptor to spatially sequester SgmT.
      We identify the DigR binding site in the promoter of the fibA gene, which encodes
      an abundant extracellular matrix metalloprotease. Whole-genome expression
      profiling experiments in combination with the identified DigR binding site
      allowed the identification of the DigR regulon and suggests that SgmT/DigR
      regulates the expression of genes for secreted proteins and enzymes involved in
      secondary metabolite synthesis. We suggest that SgmT/DigR regulates extracellular
      matrix composition and that SgmT activity is regulated by two sensor domains with
      ligand binding to the GAF domain resulting in SgmT activation and c-di-GMP
      binding to the GGDEF domain resulting in spatial sequestration of SgmT.

PMID- 22394316
TI  - Efflux transporters in the blood-brain interfaces--in vitro and in vivo methods
      and correlations.
AB  - INTRODUCTION: Sufficient brain exposure is crucial to the success of CNS drugs.
      The twofold greater attrition rate in clinical development of CNS drugs over the
      respective attrition rate of non-CNS drugs is due to lack of efficacy. It is
      generally thought that poor brain exposure is at least partly responsible for
      this, as the concentration-time profile at the brain target site is critical for
      efficacy. Efflux transporters in the blood-brain interfaces play a crucial role
      in modulation of permeability of drugs across these interfaces. Validation of
      preclinical tools to correctly predict brain exposure in humans is essential.
      AREAS COVERED: This review summarizes in vitro and in vivo tools to detect and
      characterize interactions of drugs with efflux transporters relevant to blood
      brain interfaces. Furthermore, the article discusses the strengths and weaknesses
      of these methods and the limitations of their application, in addition to
      covering in vitro - in vivo correlations. EXPERT OPINION: A more detailed
      validation of in vitro efflux transporter assays employing primary brain
      endothelial cultures is needed. This should go along with mapping uptake
      transporters expressed in the blood-brain interfaces. With the availability of
      specific inhibitors, utilization of in vivo methods such as brain microdialysis
      is increasing. Once transporter-humanized mice are available, we may witness a
      further increase in applications of in vivo methods.

PMID- 22394317
TI  - Access to "Friedel-Crafts-restricted" tert-alkyl aromatics by
      activation/methylation of tertiary benzylic alcohols.
AB  - Herein we describe a two-step protocol to prepare m-tert-alkylbenzenes. The
      appropriate tertiary benzylic alcohols are activated with SOCl(2) or concentrated
      HCl and then treated with trimethylaluminum, affording the desired products in 68
      97% yields (22 examples). This reaction sequence is successful in the presence of
      a variety of functional groups, including acid-sensitive and Lewis-basic groups.
      In addition to t-Bu groups, 1,1-dimethylpropyl and 1-ethyl-1-methylpropyl groups
      can also be installed using this method.

PMID- 22394318
TI  - Comparison of refractive outcomes using five devices for the assessment of
      preoperative corneal power.
AB  - BACKGROUND:   To compare keratometric values obtained with a manual keratometer
      (Topcon), an automated keratometer (Canon), an Orbscan II (Bausch & Lomb), the
      IOLMaster keratometer (Carl-Zeiss) and the Pentacam rotating Scheimpflug camera
      (Oculus) in cataract surgery, and to characterize the refractive outcomes
      generated using each device. DESIGN:   Retrospective study conducted at a
      tertiary university hospital. PARTICIPANTS: Sixty-nine eyes of 69 patients were
      analysed. METHODS:   The keratometric values obtained with different devices
      (manual keratometer, automated keratometer, corneal topography, IOLMaster
      keratometer and Scheimpflug camera) were employed for intraocular lens power
      calculation. Multiple comparisons of averaged keratometric value were conducted,
      and the averaged keratometric value was used to calculate the predicted
      refraction. The absolute values of corneal astigmatism were calculated and also
      compared. MAIN OUTCOME MEASURES:   Mean keratometric value, absolute value of
      astigmatism, mean error and mean absolute error from each device. RESULTS:   The
      mean keratometric values generated by manual keratometer, automated keratometry,
      corneal topography, IOLMaster keratometer and the Pentacam Scheimpflug system
      were 43.95 +/- 1.39, 43.91 +/- 1.39, 44.67 +/- 1.53, 44.03 +/- 1.41 and 42.96 +/-
      1.39 diopter, respectively. The absolute value of astigmatism determined via
      manual keratometer, automated keratometer, corneal topography, IOLMaster
      keratometer and the Pentacam Scheimpflug system were 0.95 +/- 0.60, 0.99 +/-
      0.69, 1.14 +/- 0.74, 1.11 +/- 0.65 and 1.03 +/- 0.73 diopter, respectively. The
      corneal topography showed statistically significant differences with other
      devices and produced the greater value in mean absolute errors (all P < 0.05).
      CONCLUSION:   Keratometric values with standard devices are a good choice for
      cataract surgery, whereas the corneal topography is not an appropriate method for
      the assessment of preoperative keratometric values.

PMID- 22394320
TI  - The effect of different implant-abutment connection on screw joint stability.
AB  - Abstract   Dental implants with an internal connection have been designed in
      order to establish a better stress distribution when lateral external forces act
      on the prosthesis and minimize the forces transmitted to the fastening screw. In
      the present study, ten externally and ten internally hexed implants were tested
      with a compressive force applied with an Instron Universal machine. Four cycles
      of loading-unloading were applied to each specimen, in order to achieve
      displacements of 0.5, 1, 2 and 2.5 mm. The mean loads for the first cycle were
      256.70 N for the external connection and 256 N for the internal connection
      implants. The independent t test did not reveal any significant differences among
      the two tested groups (P=.780).  For the second cycle, the mean loads needed for
      a displacement of 1mm were 818.19 N and 780.20 N, for the external connection and
      the internal connection implants respectively. The independent t test revealed
      significant differences among the two tested groups (P<.001). In the third cycle,
      the mean load values for a 2mm displacement were 1394.10 N and 1225.00 N. The
      independent t test revealed significant differences among the two tested groups
      (P<.001). The mean loads for the fourth cycle were 1488.00 N for the external
      connection and 1029.00 N for the internal connection implants. These loads were
      required for a displacement of 2.5mm. The independent t test revealed significant
      differences among the two tested groups (P<.001). The results of this in vitro
      study suggest that the internal connection design of the examined implant system
      could not prevent screw loosening during overloading. No implant or prosthesis
      failure was noticed in either group.

PMID- 22394319
TI  - Coping trajectories in later life: a 20-year predictive study.
AB  - OBJECTIVES AND METHOD: Information about aging-related change in coping is
      limited mainly to results of cross-sectional studies of age differences in
      coping, and no research has focused on predictors of aging-related change in
      coping behavior. To extend research in this area, we used longitudinal multilevel
      modeling to describe older adults' (n = 719; baseline M = 61 years) 20-year,
      intraindividual approach and avoidance coping trajectories, and to determine the
      influence of two sets of predictors (threat appraisal and stressor
      characteristics; gender and baseline personal and social resources) on level and
      rate of change in these trajectories. RESULTS: Over the 20-year study interval,
      participants declined in the use of approach coping and most avoidance coping
      strategies, but there was significant variation in this trend. In simultaneous
      predictive models, female gender, more threat appraisal, stressor severity,
      social resources, and depressive symptoms, and fewer financial resources were
      independently associated with higher initial levels of coping responses. Having
      more social resources, and fewer financial resources, at baseline in late-middle
      age predicted faster decline over time in approach coping. Having more baseline
      depressive symptoms, and fewer baseline financial resources, hastened decline in
      use of avoidance coping. Independent of other variables in these models, decline
      over time in approach coping and avoidance coping remained statistically
      significant. CONCLUSION: Overall decline in coping may be a normative pattern of
      coping change in later life. However, it also is modifiable by older adults'
      stressor appraisals, their stressors, and the personal and social resources they
      possess at entry to later life, in late-middle-age.

PMID- 22394321
TI  - Multiphoton fluorescence lifetime imaging shows spatial segregation of secondary
      metabolites in Eucalyptus secretory cavities.
AB  - Multiphoton fluorescence lifetime imaging provides an excellent tool for imaging
      deep within plant tissues while providing a means to distinguish between
      fluorophores with high spatial and temporal resolution. Ideal candidates for the
      application of multiphoton fluorescence lifetime imaging to plants are the
      embedded secretory cavities found in numerous species because they house complex
      mixtures of secondary metabolites within extracellular lumina. Previous
      investigations of this type of structure have been restricted by the use of
      sectioned material resulting in the loss of lumen contents and often
      disorganization of the delicate secretory cells; thus it is not known if there is
      spatial segregation of secondary metabolites within these structures. In this
      paper, we apply multiphoton fluorescence lifetime imaging to investigate the
      spatial arrangement of metabolites within intact secretory cavities isolated from
      Eucalyptus polybractea R.T. Baker leaves. The secretory cavities of this species
      are abundant (up to 10 000 per leaf), large (up to 6 nL) and importantly house
      volatile essential oil rich in the monoterpene 1,8-cineole, together with an
      immiscible, non-volatile component comprised largely of autofluorescent
      oleuropeic acid glucose esters. We have been able to optically section into the
      lumina of secretory cavities to a depth of ~80 MUm, revealing a unique spatial
      organization of cavity metabolites whereby the non-volatile component forms a
      layer between the secretory cells lining the lumen and the essential oil. This
      finding could be indicative of a functional role of the non-volatile component in
      providing a protective region of low diffusivity between the secretory cells and
      potentially autotoxic essential oil.

PMID- 22394322
TI  - Attachment insecurity predicts child active resistance to parental requests in a
      compliance task.
AB  - AIM: We studied the effects of early mother-child relationship quality and child
      temperament on the development of child compliance and active resistance in a
      large population-based cohort study (n = 534). BACKGROUND: Parenting and the
      quality of the parent-child relationship can either hamper or support the
      development of child compliance directly or in interplay with child temperament.
      METHODS: Mother-infant dyads were observed at 14 and 36 months and maternal and
      child behaviours were independently coded. The quality of compliance was assessed
      at 36 months in a clean-up task. Child behaviour was coded using a system
      differentiating between two dimensions: Compliance and Active Resistance.
      RESULTS: Controlling for concurrent maternal sensitivity, child temperament, and
      gender children with a more insecure attachment relationship showed higher levels
      of active resistance during Clean-Up than more securely attached children. The
      effect was stronger for boys than for girls and mainly driven by attachment
      avoidance. CONCLUSIONS: Early attachment is an important contributor to child
      socialization of moral behaviour.

PMID- 22394323
TI  - Identification of suitable formulations for high dose oral studies in rats using
      in vitro solubility measurements, the maximum absorbable dose model, and
      historical data sets.
AB  - The ability to define compound solubility targets that are predictive of good
      oral absorption at high dose preclinical studies (>= 100 mg compound/kg animal)
      is of use in drug discovery and development. Two different approaches to identify
      these targets in preclinical formulations are evaluated herein. The first
      approach is the use of solubility values from in vitro formulation dilutions
      using biorelevant parameters for rats. These dilution/solubility results are
      applied to the maximum absorbable dose (MAD) model to predict compound exposure
      (AUC) from oral doses and allow the fraction of dose absorbed (F(abs))
      calculation. The results from 26 such in vitro evaluations are compared to in
      vivo studies and discussed. The second approach is the analysis of in vivo AUC
      proportionality between 10 and 100 mg/kg doses for 28 compounds where only the
      compound solubility in neat formulation is known. Both assessments suggest
      similar threshold targets to remove solubility as an absorption limitation for
      any given compound. Specifically, compound solubility should be >2 mg/mL in
      aqueous surfactants and >15 mg/mL in cosolvent (PEG400) or pH-adjusted aqueous
      formulations. The results are a starting place for formulation rule-of-thumb
      solubility targets applied in discovery and development settings.

PMID- 22394324
TI  - K+ depolarization evokes ATP, adenosine and glutamate release from glia in rat
      hippocampus: a microelectrode biosensor study.
AB  - BACKGROUND AND PURPOSE: This study was undertaken to characterize the ATP,
      adenosine and glutamate outflow evoked by depolarization with high K(+)
      concentrations, in slices of rat hippocampus. EXPERIMENTAL APPROACH: We utilized
      the microelectrode biosensor technique and extracellular electrophysiological
      recording for the real-time monitoring of the efflux of ATP, adenosine and
      glutamate. KEY RESULTS: ATP, adenosine and glutamate sensors exhibited transient
      and reversible current during depolarization with 25 mM K(+) , with distinct
      kinetics. The ecto-ATPase inhibitor ARL67156 enhanced the extracellular level of
      ATP and inhibited the prolonged adenosine efflux, suggesting that generation of
      adenosine may derive from the extracellular breakdown of ATP. Stimulation-evoked
      ATP, adenosine and glutamate efflux was inhibited by tetrodotoxin, while exposure
      to Ca(2+) -free medium abolished ATP and adenosine efflux from hippocampal
      slices. Extracellular elevation of ATP and adenosine were decreased in the
      presence of NMDA receptor antagonists, D-AP-5 and ifenprodil, whereas non-NMDA
      receptor blockade by CNQX inhibited glutamate but not ATP and adenosine efflux.
      The gliotoxin fluoroacetate and P2X7 receptor antagonists inhibited the K(+) 
      evoked ATP, adenosine and glutamate efflux, while carbenoxolone in low
      concentration and probenecid decreased only the adenosine efflux. CONCLUSIONS AND
      IMPLICATIONS: Our results demonstrated activity-dependent gliotransmitter release
      in the hippocampus in response to ongoing neuronal activity. ATP and glutamate
      were released by P2X7 receptor activation into extracellular space. Although the
      increased extracellular levels of adenosine did derive from released ATP,
      adenosine might also be released directly via pannexin hemichannels.

PMID- 22394325
TI  - Anesthesia for Treacher Collins syndrome: a review of airway management in 240
      pediatric cases.
AB  - OBJECTIVES: To review airway management with anesthesia for children with
      Treacher Collins syndrome (TCS) and determine whether intubation was more
      difficult with increasing age. BACKGROUND: Treacher Collins syndrome is a rare
      disorder of craniofacial development characterized by maxillary, zygomatic, and
      mandibular dysplasia. TCS is associated with difficult intubation, but reports of
      airway management are limited to case reports and small cases series. Children
      with TCS may require multiple general anesthetics, and it has been suggested that
      intubation becomes more difficult with increasing age. METHODS: A retrospective
      case note review of children with TCS from birth to 18 years undergoing
      anesthesia from 1971 to 2011 in a single center was performed. Demographic data,
      procedure type, anesthesia type, method of airway management, modified Cormack
      Lehane (MCL) grade of laryngoscopic view, and any other descriptions of airway
      difficulty or complications were collated. RESULTS: Of 59 patients with TCS, 35
      children underwent a total of 240 anesthetics, most commonly for craniofacial
      surgery. Final airway management consisted of face mask 17%, laryngeal mask
      airway 16%, endotracheal intubation 49%, and 18% had a preexisting tracheostomy.
      The laryngeal mask airway provided an adequate airway in all cases when it was
      used. MCL grade was recorded in 97 cases involving 28 patients: 7% grade 1, 9%
      grade 2a, 31% grade 2b, 26% grade 3, and 27% grade 4. Fifteen (54%) patients were
      MCL grade 4 on at least one occasion. Failed intubation occurred in 6 (5%) of 123
      cases of planned intubation. The procedure was canceled in two cases (0.8%)
      because of failure to intubate. Intubation techniques other than conventional
      direct laryngoscopy were used in 41% of cases. MCL grade increased with
      increasing age (P = 0.007). CONCLUSIONS: Most children with TCS have difficult
      laryngoscopic views with many requiring specialized intubation techniques. Direct
      laryngoscopy becomes more difficult with increasing age. The laryngeal mask
      airway is a good choice of airway when endotracheal intubation is not required.

PMID- 22394326
TI  - Salivary antioxidant biomarkers in non-ferrous metals mine workers--a pilot
      study.
AB  - OBJECTIVE: The purpose of the present study is to evaluate the relationships
      between occupational exposure to mine dust, salivary antioxidants and their
      possible implications in the pathogenicity of different exposure diseases.
      MATERIAL AND METHODS: We studied 30 individuals with long-term occupational
      exposure to non-ferrous metal mine conditions and a control group consisted of 30
      healthy volunteers. Salivary uric acid, gammaglutamyltransferase (GGT), albumin
      and the total antioxidant capacity (TAC) were measured. RESULTS: Statistically
      significant differences in salivary GGT (P = 0.004), TAC (P < 0.001) and uric
      acid (P = 0.02) were noted between the two groups. A strong positive correlation
      between TAC and uric acid was recorded in controls (r = 0.76, P = 0.0002).
      CONCLUSIONS: Saliva may provide an important line of antioxidant defense in
      humans exposed to oxidant threats. These components may also serve as convenient
      biomarkers to monitor oxidant exposure.

PMID- 22394328
TI  - Straight sprinting is the most frequent action in goal situations in professional
      football.
AB  - The present study aimed to analyse the influence of speed and power abilities in
      goal situations in professional football. During the second half of the season
      2007/08, videos of 360 goals in the first German national league were analysed by
      visual inspection. For the assisting and the scoring player the situations
      immediately preceding the goal were evaluated. The observed actions were
      categorised as: no powerful action, rotation (around the body's centre-line),
      straight sprint, change-in-direction sprint, jump, or a combination of those
      categories. Two hundred and ninety-eight (83%) goals were preceded by at least
      one powerful action of the scoring or the assisting player. Most actions for the
      scoring player were straight sprints (n = 161, 45% of all analysed goals, P <
      0.001) followed by jumps (n = 57, 16%), rotations and change-in-direction sprints
      (n = 22, 6% each). Most sprints were conducted without an opponent (n = 109, P <
      0.001) and without the ball (n = 121, P < 0.001). Similarly, for the assisting
      player the most frequent action was a straight sprint (n = 137, P < 0.001)
      followed by rotations (n = 28), jumps (n = 22) and change-in-direction sprints (n
      = 18). The straight sprints were mostly conducted with the ball (n = 93, P =
      0.003). In conclusion, straight sprinting is the most frequent action in goal
      situations. Power and speed abilities are important within decisive situations in
      professional football and, thus, should be included in fitness testing and
      training.

PMID- 22394327
TI  - Structural and biochemical characterization of the childhood cataract-associated
      R76S mutant of human gammaD-crystallin.
AB  - Although a number of gammaD-crystallin mutations are associated with cataract
      formation, there is not a clear understanding of the molecular mechanism(s) that
      lead to this protein deposition disease. As part of our ongoing studies on
      crystallins, we investigated the recently discovered Arg76 to Ser (R76S) mutation
      that is correlated with childhood cataract in an Indian family. We expressed the
      R76S gammaD-crystallin protein in E. coli, characterized it by CD, fluorescence,
      and NMR spectroscopy, and determined its stability with respect to thermal and
      chemical denaturation. Surprisingly, no significant biochemical or biophysical
      differences were observed between the wild-type protein and the R76S variant,
      except a lowered pI (6.8 compared to the wild-type value of 7.4). NMR assessment
      of the R76S gammaD-crystallin solution structure, by RDCs, and of its motional
      properties, by relaxation measurements, also revealed a close resemblance to wild
      type crystallin. Further, kinetic unfolding/refolding experiments for R76S and
      wild-type protein showed similar degrees of off-pathway aggregation suppression
      by alphaB-crystallin. Overall, our results suggest that neither structural nor
      stability changes in the protein are responsible for the R76S gammaD-crystallin
      variant's association with cataract. However, the change in pI and the associated
      surface charge or the altered nature of the amino acid could influence
      interactions with other lens protein species.

PMID- 22394330
TI  - Solvent exfoliation of transition metal dichalcogenides: dispersibility of
      exfoliated nanosheets varies only weakly between compounds.
AB  - We have studied the dispersion and exfoliation of four inorganic layered
      compounds, WS(2), MoS(2), MoSe(2), and MoTe(2), in a range of organic solvents.
      The aim was to explore the relationship between the chemical structure of the
      exfoliated nanosheets and their dispersibility. Sonication of the layered
      compounds in solvents generally gave few-layer nanosheets with lateral dimensions
      of a few hundred nanometers. However, the dispersed concentration varied greatly
      from solvent to solvent. For all four materials, the concentration peaked for
      solvents with surface energy close to 70 mJ/m(2), implying that all four have
      surface energy close to this value. Inverse gas chromatography measurements
      showed MoS(2) and MoSe(2) to have surface energies of ~75 mJ/m(2), in good
      agreement with dispersibility measurements. However, this method suggested
      MoTe(2) to have a considerably larger surface energy (~120 mJ/m(2)). While
      surface-energy-based solubility parameters are perhaps more intuitive for two
      dimensional materials, Hansen solubility parameters are probably more useful. Our
      analysis shows the dispersed concentration of all four layered materials to show
      well-defined peaks when plotted as a function of Hansen's dispersive, polar, and
      H-bonding solubility parameters. This suggests that we can associate Hansen
      solubility parameters of delta(D) ~ 18 MPa(1/2), delta(P) ~ 8.5 MPa(1/2), and
      delta(H) ~ 7 MPa(1/2) with all four types of layered material. Knowledge of these
      properties allows the estimation of the Flory-Huggins parameter, chi, for each
      combination of nanosheet and solvent. We found that the dispersed concentration
      of each material falls exponentially with chi as predicted by solution
      thermodynamics. This work shows that solution thermodynamics and specifically
      solubility parameter analysis can be used as a framework to understand the
      dispersion of two-dimensional materials. Finally, we note that in good solvents,
      such as cyclohexylpyrrolidone, the dispersions are temporally stable with >90% of
      material remaining dispersed after 100 h.

PMID- 22394329
TI  - Understanding the phenotypic structure of adult retrospective ADHD symptoms
      during childhood in the United States.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous
      disorder, and the phenotypic structure comprising inattentive and hyperactive
      impulsive type symptoms has been the focus of a growing body of recent research.
      Methodological studies are needed to better characterize phenotypes to advance
      research as well as clinical practice. A large U.S. population-based sample of
      young adults (N = 14,307, aged 17-28 years, 52.8% female) retrospectively
      reported their experiences of childhood ADHD symptoms. Factor analysis, latent
      class analysis, and factor mixture modeling of ADHD symptoms were compared to
      determine which underlying structure best fit the data. Fit statistics as well as
      substantive criteria compared models within and across model subtypes. Analyses
      supported a two-factor two-class structure for both male and female subjects. The
      two latent factors represented inattentive and hyperactive-impulsive symptom
      dimensions. The two latent classes divided people into a smaller affected class
      and a larger unaffected class. Individuals who reported having been diagnosed
      with ADHD were more likely to be in the affected class (OR male subjects = 4.03,
      95% CI [2.65, 6.13]; OR female subjects = 5.65, 95% CI [3.15, 10.10]). This work
      aids in the understanding of ADHD symptomatology within the population; a
      majority of people experience very low symptom severity, whereas a minority of
      people experience high symptom severity. Within this high symptom group, however,
      variability in symptom experiences exists. Empirical models can be helpful in
      clarifying ADHD phenotypic structure that has the potential to advance research
      on the etiology and consequences of ADHD symptoms.

PMID- 22394331
TI  - Nickel-mediated hydrogenolysis of C-O bonds of aryl ethers: what is the source of
      the hydrogen?
AB  - Mechanistic studies of the hydrogenolysis of aryl ethers by nickel were
      undertaken with (diphosphine)aryl methyl ethers. A Ni(0) complex containing Ni
      arene interactions adjacent to the aryl-O bond was isolated. Heating led to aryl
      O bond activation and generation of a nickel aryl methoxide complex. Formal beta
      H elimination from this species produced a nickel aryl hydride which can undergo
      reductive elimination in the presence of formaldehyde to generate a carbon
      monoxide adduct of Ni(0). The reported complexes map out a plausible mechanism of
      aryl ether hydrogenolysis catalyzed by nickel. Investigations of a previously
      reported catalytic system using isotopically labeled substrates are consistent
      with the mechanism proposed in the stoichiometric system, involving beta-H
      elimination from a nickel alkoxide rather than cleavage of the Ni-O bond by H(2).

PMID- 22394332
TI  - Detailed evaluation of a newly attained fungal pigment from Monascus purpureus in
      meat burgers.
AB  - Beef burgers with red pigment extracted from Monascus purpureus, used as a
      natural colouring agent, were examined for chemical compositions, physical
      properties, microbiological aspects and organoleptic evaluation. Beef burgers
      with Monascus pigment showed higher nutritional values compared with control
      samples. Nutritional values were proportionally enhanced by increasing pigment
      concentration. Synthetic dye samples had the lowest values of nutrients. Cooking
      loss percentage and water holding capacity were lower in all treatments compared
      with control samples, and vice versa for plasticity. The initial total bacterial
      count, Staphylococcus aureus count and coliform count were determined. Extending
      storage period up to 90 days severely reduced all tested microorganisms. By
      increasing the M. pigment concentration, the colour was significantly increased.
      Insignificant differences in colours were noticed among various treatments.
      Flavour and body and texture scores were insignificantly different. Microbial
      inhibition percentage of beef burger samples was increased by increasing the
      Monascus pigment concentration up to 0.8 g/kg.

PMID- 22394334
TI  - Predictive value of the vitamin K epoxide reductase complex subunit 1 G-1639A and
      C1173T single nucleotide polymorphisms in retinal vein occlusion.
AB  - BACKGROUND:   To determine if vitamin K epoxide reductase complex subunit 1 gene
      polymorphisms have an effect on the risk of having a retinal vein occlusion.
      DESIGN:   Case-control study. PARTICIPANTS:   The study population consisted of
      68 patients who were newly diagnosed with retinal vein occlusion and 66 sex
      matched controls. METHODS:   Genomic DNA was extracted from peripheral leukocytes
      from ethylenediamine tetra-acetic acid-anticoagulated blood. Genotyping of the
      vitamin K epoxide reductase complex subunit 1 G-1639A (rs 9923231) and C1173T (rs
      9934438) single nucleotide polymorphisms was performed using real-time polymerase
      chain reaction and commercially available kits. MAIN OUTCOME MEASURES:   A full
      ophthalmological evaluation was performed in each subject, and all subjects were
      screened for hypertension, hypercholesterolaemia and diabetes. The genotypes of
      the vitamin K epoxide reductase complex subunit 1 single nucleotide polymorphisms
      were determined. RESULTS:   The vitamin K epoxide reductase complex subunit 1 GG
      and CC genotypes were more frequent (41% vs. 21%; P = 0.021), and the combined
      GA/AA and CT/CC genotypes were less frequent in patients with retinal vein
      occlusion than in control subjects. After adjusting for hypertension, age, plasma
      fibrinogen levels and prevalence of diabetes and hypercholesterolaemia, the GG
      and CC genotypes were found to be an independent predictor of retinal vein
      occlusion (B = 2.28; odds ratio = 9.79; P = 0.003; 95% confidence interval: 2.22
      43.24). CONCLUSION:   It was found that subjects with the vitamin K epoxide
      reductase complex subunit 1 GG and CC genotypes had a higher risk of retinal vein
      occlusion.

PMID- 22394335
TI  - Electrophilic fluoroalkylation of Ni(II) N-confused porphyrins with
      fluoroalkylarylsulfonium salts.
AB  - Experimental studies showed that Ni(II) N-confused porphyrins, treated with
      fluoroalkylarylsulfonium salts, can undergo an electrophilic fluoroalkylation at
      the inner 21-C position, leading to 21-fluoroalkylated Ni(II) N-confused
      porphyrins.

PMID- 22394336
TI  - Tyrosine hydroxylase assay: a bioassay for aryl hydrocarbon receptor-active
      compounds based on tyrosine hydroxylase promoter activation.
AB  - Tyrosine hydroxylase (TH) assay is a novel bioassay for screening aryl
      hydrocarbon receptor (AhR)-active compounds with diverse toxicities. The TH assay
      employs reporter genes to evaluate TH promoter activity, which is linked to
      dopamine synthesis and regulated by the AhR-aryl hydrocarbon receptor responsive
      element-III (AHRE-III)-mediated pathway. The toxic equivalency factors for higher
      chlorinated dioxin congeners in the TH assay (TH-TEF) exhibit the same tendency
      as those for the WHO-TEF, indicating that the activity of the TH assay is
      consistent with that of existing methods. Furthermore, other chemicals, such as
      lower chlorinated dioxin congeners that were minimally investigated in the past
      could be detected preferentially by this assay.

PMID- 22394337
TI  - In praise of H2O2, the versatile ROS, and its vanadium complexes.
AB  - Hydrogen peroxide (H2O2) is generated in mitochondria in aerobic cells as a minor
      product of electron transport, is inhibited selectively by phenolic acids (in
      animals) or salicylhydroxamate (in plants) and is regulated by hormones and
      environmental conditions. Failure to detect this activity is due to presence of
      H2O2-consuming reactions or inhibitors present in the reaction mixture. H2O2 has
      a role in metabolic regulation and signal transduction reactions. A number of
      enzymes and cellular activities are modified, mostly by oxidizing the protein
      thiol groups, on adding H2O2 in mM concentrations. On complexing with vanadate,
      also occurring in traces, H2O2 forms diperoxovanadate (DPV), stable at
      physiological pH and resistant to degradation by catalase. DPV was found to
      substitute for H2O2 at concentrations orders of magnitude lower, and in presence
      of catalase, as a substrate for user reaction, horseradish peroxidase (HRP), and
      in inactivating glyceraldehyde-3-phosphate dehydrogenase. superoxide dismutase
      (SOD)-sensitive oxidation of NADH was found to operate as peroxovanadate cycle
      using traces of DPV and decameric vanadate (V10) and reduces O2 to peroxide (DPV
      in presence of free vanadate). This offers a model for respiratory burst.
      Diperoxovanadate reproduces several actions of H2O2 at low concentrations:
      enhances protein tyrosine phosphorylation, activates phospholipase D, produces
      smooth muscle contraction, and accelerates stress induced premature senescence
      (SIPS) and rounding in fibroblasts. Peroxovanadates can be useful tools in the
      studies on H2O2 in cellular activities and regulation.

PMID- 22394338
TI  - Effect of selective and non-selective cyclooxygenase inhibitors on doxorubicin
      induced cardiotoxicity and nephrotoxicity in rats.
AB  - CONTEXT: Doxorubicin (DX) is a highly effective chemotherapeutic agent used
      widely in the treatment of solid tumors; however, its optimal use was associated
      with cardiotoxicity and nephrotoxicity. The exact mechanism of DX-induced
      cardiotoxicity and nephrotoxicity is not fully explored. Induction of
      cyclooxygenase-2 (COX-2) activity in either cardiac or renal tissue by DX has
      been previously reported, indicating a possible role of COX-2 in DX-induced
      tissue injury. However, the nature of this role in either tissue injury is an
      issue of controversy. OBJECTIVE: This study was the first that simultaneously
      evaluated the effects of a selective COX-2 inhibitor, nimesulide, and a non
      selective COX-inhibitor, indomethacin, on DX-induced cardiotoxicity and
      nephrotoxicity in male Wistar rats. MATERIALS AND METHODS: Rats were allocated
      into four groups. Control group, DX group (received 15 mg/kg, ip), DX +
      nimesulide (10 mg/kg/day, po) group, and DX + indomethacin (2 mg/kg/day, po)
      group. Nimesulide and indomethacin were started at the same day of DX injection
      and continued for 5 days. RESULTS: The results of the present study showed that
      inhibition of COX-2 either by selective or non-selective COX-2 inhibitor
      ameliorated DX-induced cardiotoxicity but aggravated DX-induced nephrotoxicity in
      rats, as evidenced biochemically and histopathologically. DISCUSSION AND
      CONCLUSION: Our study indicates that production of COX-2 is organ specific;
      consequently, the differential effect of COX-inhibitors should be considered in
      DX-treated patients. However, a wide scale experiment is needed for further
      confirmation and testing other members of COX-inhibitors (e.g. celecoxib and
      diclofenac).

PMID- 22394339
TI  - Assessment of the adverse effects of the acaricide amitraz: in vitro evaluation
      of genotoxicity.
AB  - Amitraz is a formamidine widely used in Veterinary Medicine for the treatment of
      ectoparasites. It is a highly liposoluble compound that is quickly absorbed
      through the skin and mucous membranes, thus making exposure potentially dangerous
      for humans and animals. The aim of this study was to compare the genotoxic
      potential of the active constituent of the insecticide amitraz and a commercial
      product containing amitraz in vitro in hamster cells. The induction of primary
      DNA damage was evaluated by alkaline single-cell gel electrophoresis (comet
      assay) and the apoptotic ability was examined by the Annexin V/propidium iodide
      staining assay. The commercial formulation significantly increased the index of
      DNA damage at concentrations of 2.50-3.75 ug/mL compared to the control. The
      active constituent only induced significant DNA damage with the highest
      concentration (3.75 ug/mL). Although both tested products increased the frequency
      of cell death, neither of them induced significant differences. Genotoxic
      potential is a primary risk factor for long-term effects such as carcinogenic and
      reproductive toxicology. Results presented here highlight the need for further
      investigation of the potential health risk of this veterinary medicine.

PMID- 22394340
TI  - Diabetes, oxidative stress, molecular mechanism, and cardiovascular disease--an
      overview.
AB  - In recent years, diabetes and its associated complications have come to represent
      a major public health concern. It is a complex disease characterized by multiple
      metabolic derangements and is known to impair cardiac function by disrupting the
      balance between pro-oxidants and antioxidants at the cellular level. The
      subsequent generation of reactive oxygen species (ROS) and accompanying oxidative
      stress are hallmarks of the molecular mechanisms responsible for cardiovascular
      disease. Among several oxidative stress-mediated mechanisms that have been
      proposed, ROS-mediated oxidative stress has received the most attention. ROS have
      been shown to interact with proteins, lipids, and DNA, causing damage to the
      cellular macromolecules and subsequently, deterioration of cellular function.
      Induction of thioredoxin-1 (Trx1) gene expression has been demonstrated to
      protect the diabetic myocardium from dysfunction by reducing oxidative stress and
      enhancing the expression of heme oxygenase-1 (HO-1) and vascular endothelial
      growth factor (VEGF). The failure of antioxidants to consistently demonstrate
      clinical benefit necessitates further investigation of the role of oxidative
      stress in diabetes-mediated cardiovascular disease.

PMID- 22394341
TI  - Benzo(a)pyrene induces hepatic AKR1A1 mRNA expression in tilapia fish
      (Oreochromis niloticus).
AB  - AKR1A1 or aldehyde reductase is a member of the aldo-keto reductases superfamily
      that is evolutionarily conserved among species. AKR1A1 is one of the five AKRs
      (AKR1A1 and 1C1-1C4) implicated in the metabolic benzo(a)pyrene (BaP) activation
      to reactive BaP 7,8-dione. BaP is a polycyclic aromatic hydrocarbon (PAH) widely
      distributed in aquatic ecosystems and its metabolic activation is necessary to
      produce its toxic effects. Although the presence of AKR1A1 in fish has been
      reported, its tissue distribution in tilapia (Oreochromis niloticus) and AKR1A1
      inducibility by BaP are not known yet. Moreover, cytochrome P4501A (CYP1A) mRNA
      expression in fish has been used as a PAH biomarker of effect. Therefore, BaP
      effects on AKR1A1 and CYP1A gene expressions in tilapia, a species of commercial
      interest, were investigated by real-time RT-PCR. A partial AKR1A1 cDNA was
      identified, sequenced and compared with AKR1A1 reported sequences in the GenBank
      DNA database. Constitutive AKR1A1 mRNA expression was detected mainly in liver,
      similarly to that of CYP1A. BaP exposure resulted in statistically significant
      AKR1A1 and CYP1A mRNA induction in liver (20- and 120-fold, respectively) at 24
      h. On the other hand, ethoxyquin (EQ) was used as control inducer for AKR1A1
      mRNA. Interestingly, EQ also induced CYP1A mRNA levels in tilapia liver. Our
      results suggest that teleost AKR1A1, in addition to CYP1A, are inducible by BaP.
      The mechanism of AKR1A1 induction by BaP and its role in fish susceptibility to
      BaP toxic effects remains to be elucidated.

PMID- 22394342
TI  - Heme oxygenase-1 in environmental toxin-induced lung disease.
AB  - In the US, lung disease is the number three killer and accounts for one of every
      six deaths. Furthermore, more than 35 million US populations are now living with
      a chronic lung disease. Therefore, it is of urgent need to develop novel
      strategies that can protect against the development and progression of lung
      disease. Inhalation of air pollutants or environmental toxins induces
      inflammation and oxidative stress in the lung, resulting in tissue damage with
      subsequent decline in lung function. Heme oxygenase-1 (HO-1) is a stress response
      protein, which is highly inducible in response to pathological stimulation. Due
      to the cumulative effects of HO-1 on heme catabolism and the generation of
      biologically active downstream products, induction of HO-1 might serve as a
      protective mechanism against oxidative stress and inflammation-induced injury.
      Accumulating evidences have indicated a protective function of HO-1 against lung
      injury. This review highlights the roles of HO-1 in lung disease induced by
      environmental toxins such as cigarette smoke (CS), silica, and asbestos.

PMID- 22394343
TI  - The protective effects of hydroxytyrosol against ortho-phenylphenol-induced DNA
      damage in HepG2 cells.
AB  - Ortho-phenylphenol (OPP) has been found to cause carcinomas in the urinary tract
      of rats. Since OPP is a potent genotoxic compound, and used as fungicides and
      antibacterial agents in fruits and fruit products, search for newer, better
      agents for protection against toxicity of OPP is required. In this study, the
      chemoprotective effect of hydroxytyrosol (HT) against OPP-induced DNA damage in
      HepG2 cells was investigated. Comet assay was used to detect the DNA damage
      induced by OPP. To elucidate the possible mechanisms, we tested lysosomal
      membrane stability, mitochondrial membrane potential, intracellular generation of
      reactive oxygen species (ROS), and reduced glutathione (GSH). Results showed that
      HT significantly reduced the DNA strand breaks caused by OPP. Moreover, HT
      effectively suppressed OPP-induced ROS formation, and increased the GSH level.
      Lysosomal membrane and mitochondrial membrane were also protected when cells were
      pretreated with HT. These results suggested that the disruption of lysosomal
      membrane integrity and the oxidative stress, leading to DNA fragmentation, may be
      the mechanism of DNA damage induced by OPP. The antioxidant activity of HT may
      play an important part in attenuating the DNA damage of OPP.

PMID- 22394344
TI  - Oxidative stress and cardiac hypertrophy: a review.
AB  - Cardiac hypertrophy (CH) is an adaptive response of the heart to pressure
      overload. It is a common pathological feature in the natural course of some major
      cardiovascular diseases, like, hypertension and myocardial infarction. Cardiac
      hypertrophy is strongly associated with an increased risk of heart failure and
      sudden cardiac death. The complex and dynamic pathophysiological mechanisms of CH
      has been the focus of intense scientific investigation, in an effort to design
      preventive and curative strategies. Oxidative stress has been identified as one
      of the key contributing factors in the development of cardiac hypertrophy. In
      this review, evidences supporting the oxidative stress as a cause of cardiac
      hypertrophy with emphasis on mitochondrial oxidative stress and possible options
      for pharmacological interventions have been discussed. Reactive oxygen species
      (ROS) also activate a broad variety of hypertrophy signaling kinases and
      transcription factors, like, MAP kinase, NF K-B, etc. In addition to profound
      alteration of cellular function, ROS modulate the extracellular matrix function,
      evidenced by increased interstitial and perivascular fibrosis. Translocator
      protein (TSPO) present in the outer mitochondrial membrane is known to be
      involved in oxidative stress and cardiovascular pathology. Recently, its role in
      cardiac hypertrophy has been reported by us. All these evidences strongly provide
      support to beneficial role of drugs which selectively interfere with the
      generation of free radicals or augment endogenous antioxidants in cardiac
      hypertrophy.

PMID- 22394345
TI  - Di(2-ethylhexyl)phthalate-induced renal oxidative stress in rats and protective
      effect of selenium.
AB  - This study was designed to examine the oxidative stress potential of di(2
      ethylhexyl)phthalate (DEHP) on rat kidney and to evaluate possible protective
      effect of selenium (Se) status. Se deficiency (SeD) was produced in 3-week old
      Sprague-Dawley rats by feeding them <= 0.05 Se mg/kg diet for 5 weeks; Se
      supplementation group (SeS) was on 1 mg Se/kg diet. DEHP treated groups received
      1000 mg/kg dose by gavage during the last 10 days of the feeding period.
      Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1),
      glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR)], catalase (CAT),
      superoxide dismutase (SOD), and glutathione S-transferase (GST); concentrations
      of total glutathione (GSH), thiols and thiobarbituric acid reactive substance
      (TBARS) levels were measured. DEHP treatment was found to induce oxidative stress
      in rat kidney, as evidenced by significant decreases in GPx1 (~20%) and SOD
      (~30%) activities and GSH levels (~20%), along with marked decrease in thiol
      content (~40%) and increase in TBARS (~30%) levels. The effects of DEHP was more
      pronounced in SeD rats, whereas Se supplementation was protective by providing
      substantial elevations of GPx1 and GPx4 activities and GSH levels. These findings
      emphasized the critical role of Se as an effective redox regulator and the
      importance of Se status in protecting renal tissue from the oxidant stressor
      activity of DEHP.

PMID- 22394346
TI  - Testing of the estrogenic activity and toxicity of Stephania venosa herb in
      ovariectomized rats.
AB  - Stephania venosa Spreng is a traditional herb which has been used for cancer
      treatment as well as an aphrodisiac. The scientific literature strongly supports
      its in vitro antiproliferative effects on cancer cell lines and has suggested
      developing this plant as a potential anticancer drug. However, the in vivo
      steroidogenic activity and toxicity of this plant have never been tested. We
      analyzed the levels of five key isoflavones in the plant extract by quantitative
      HPLC and then evaluated the in vivo estrogenic activity and toxicity in
      ovariectomized rats, in comparison with the phytoestrogen-rich plant, Pueraria
      mirifica. Twenty rats were first ovariectomized, and then seven days later
      divided into four groups and gavaged daily with 0, 10 and 100 mg/kg body
      weight/day of S. venosa, or 100 mg/kg body weight/day of P. mirifica for 28 days.
      A trace amount of puerarin, daidzin and daidzein with a subtle amount of
      genistein and genistin were isolated from the S. venosa tuber extract. S. venosa
      tuber powder, at both doses, did not exhibit any detectable estrogenic activity
      in ovariectomized rats, as assessed by the vaginal cytology and uterotropic
      assays, whilst P. mirifica induced a remarkable vaginal and uterine
      proliferation. S. venosa induced a toxicological effect on the hematological
      values and histopathological appearance of metabolic organs. Taken together,
      these results suggest that S. venosa has no discernable estrogenic activity but
      that it is toxic, at least to ovariectomized rats. Thus, the use of this plant
      for anticancer treatment needs to be reassessed or used with caution.

PMID- 22394347
TI  - Effects of long term ethanol consumption mediated oxidative stress on neovessel
      generation in liver.
AB  - Angiogenesis, the growth of new blood vessels, is essential during tissue repair.
      Though most molecular mechanisms of angiogenesis are common to the liver and
      other organs, there was no report available whether alcoholic liver disease also
      causes angiogenesis. In this study, we examined the effects of long term ethanol
      (1.6 g/kg body weight/day) consumption on angiogenic responses in the liver of
      male Wistar strain albino rats (16-18 weeks old, weighing 200-220 g) up to 36
      weeks. Chronic ethanol consumption was associated with not only elevated
      oxidative stress, and altered cytokines expression, but also developed large von
      Willebrand factor, fibrosis and activation of matrix metalloproteinases.
      Moreover, vascular endothelial growth factor-receptor 2 (VEGF-R2, fetal liver
      kinase 1: Flk-1/KDR) expression and neovessel generation in the rat liver were
      noted after 36 weeks of ethanol consumption. Thus our study provides novel
      evidence that long-term ethanol consumption is associated with angiogenesis
      through delicate and coordinated action of a variety of mediators.

PMID- 22394348
TI  - The ingestion of combined carbohydrates does not alter metabolic responses or
      performance capacity during soccer-specific exercise in the heat compared to
      ingestion of a single carbohydrate.
AB  - This study was designed to investigate the effect of ingesting a glucose plus
      fructose solution on the metabolic responses to soccer-specific exercise in the
      heat and the impact on subsequent exercise capacity. Eleven male soccer players
      performed a 90 min soccer-specific protocol on three occasions. Either 3 ml . kg(
      1) body mass of a solution containing glucose (1 g . min(-1) glucose) (GLU), or
      glucose (0.66 g . min(-1)) plus fructose (0.33 g . min(-1)) (MIX) or placebo
      (PLA) was consumed every 15 minutes. Respiratory measures were undertaken at 15
      min intervals, blood samples were drawn at rest, half-time and on completion of
      the protocol, and muscle glycogen concentration was assessed pre- and post
      exercise. Following the soccer-specific protocol the Cunningham and Faulkner test
      was performed. No significant differences in post-exercise muscle glycogen
      concentration (PLA, 62.99 +/- 8.39 mmol . kg wet weight(-1); GLU 68.62 +/- 2.70;
      mmol . kg wet weight(-1) and MIX 76.63 +/- 6.92 mmol . kg wet weight(-1)) or
      exercise capacity (PLA, 73.62 +/- 8.61 s; GLU, 77.11 +/- 7.17 s; MIX, 83.04 +/-
      9.65 s) were observed between treatments (P > 0.05). However, total carbohydrate
      oxidation was significantly increased during MIX compared with PLA (P < 0.05).
      These results suggest that when ingested in moderate amounts, the type of
      carbohydrate does not influence metabolism during soccer-specific intermittent
      exercise or affect performance capacity after exercise in the heat.

PMID- 22394349
TI  - C60 exposure induced tissue damage and gene expression alterations in the
      earthworm Lumbricus rubellus.
AB  - Effects of C60 exposure (0, 15 or 154 mg/kg soil) on the earthworm Lumbricus
      rubellus were assessed at the tissue and molecular level, in two experiments. In
      the first experiment, earthworms were exposed for four weeks, and in the second
      lifelong. In both experiments, gene expression of heat shock protein 70 (HSP70)
      decreased. For catalase and glutathione-S-transferase (GST), no significant
      trends in gene expression or enzyme activity were observed. Gene expression of
      coelomic cytolytic factor-1 (CCF-1) did not alter in earthworms exposed for four
      weeks, but was significantly down-regulated in the lifelong exposure. Histology
      of earthworms exposed to C60 in both experiments showed a damaged cuticle, with
      underlying pathologies of epidermis and muscles, as well as effects on the gut
      barrier. However, tissue repair was also observed in these earthworms. Overall,
      these data show that sub-lethal C60 exposure to earthworms via the soil affects
      gene expression and causes tissue pathologies.

PMID- 22394350
TI  - Synthesis, characterization, and reactivity of Fe complexes containing cyclic
      diazadiphosphine ligands: the role of the pendant base in heterolytic cleavage of
      H2.
AB  - The iron complexes CpFe(P(Ph)(2)N(Bn)(2))Cl (1-Cl), CpFe(P(Ph)(2)N(Ph)(2))Cl (2
      Cl), and CpFe(P(Ph)(2)C(5))Cl (3-Cl)(where P(Ph)(2)N(Bn)(2) is 1,5-dibenzyl-1,5
      diaza-3,7-diphenyl-3,7-diphosphacyclooctane, P(Ph)(2)N(Ph)(2) is 1,3,5,7
      tetraphenyl-1,5-diaza-3,7-diphosphacyclooctane, and P(Ph)(2)C(5) is 1,4-diphenyl
      1,4-diphosphacycloheptane) have been synthesized and characterized by NMR
      spectroscopy, electrochemical studies, and X-ray diffraction. These chloride
      derivatives are readily converted to the corresponding hydride complexes
      [CpFe(P(Ph)(2)N(Bn)(2))H (1-H), CpFe(P(Ph)(2)N(Ph)(2))H (2-H),
      CpFe(P(Ph)(2)C(5))H (3-H)] and H(2) complexes
      [CpFe(P(Ph)(2)N(Bn)(2))(H(2))]BAr(F)(4), [1-H(2)]BAr(F)(4), (where BAr(F)(4) is
      B[(3,5-(CF(3))(2)C(6)H(3))(4)](-)), [CpFe(P(Ph)(2)N(Ph)(2))(H(2))]BAr(F)(4), [2
      H(2)]BAr(F)(4), and [CpFe(P(Ph)(2)C(5))(H(2))]BAr(F)(4), [3-H(2)]BAr(F)(4), as
      well as [CpFe(P(Ph)(2)N(Bn)(2))(CO)]BAr(F)(4), [1-CO]Cl. Structural studies are
      reported for [1-H(2)]BAr(F)(4), 1-H, 2-H, and [1-CO]Cl. The conformations adopted
      by the chelate rings of the P(Ph)(2)N(Bn)(2) ligand in the different complexes
      are determined by attractive or repulsive interactions between the sixth ligand
      of these pseudo-octahedral complexes and the pendant N atom of the ring adjacent
      to the sixth ligand. An example of an attractive interaction is the observation
      that the distance between the N atom of the pendant amine and the C atom of the
      coordinated CO ligand for [1-CO]BAr(F)(4) is 2.848 A, considerably shorter than
      the sum of the van der Waals radii of N and C atoms. Studies of H/D exchange by
      the complexes [1-H(2)](+), [2-H(2)](+), and [3-H(2)](+) carried out using H(2)
      and D(2) indicate that the relatively rapid H/D exchange observed for [1-H(2)](+)
      and [2-H(2)](+) compared to [3-H(2)](+) is consistent with intramolecular
      heterolytic cleavage of H(2) mediated by the pendant amine. Computational studies
      indicate a low barrier for heterolytic cleavage of H(2). These mononuclear Fe(II)
      dihydrogen complexes containing pendant amines in the ligands mimic crucial
      features of the distal Fe site of the active site of the [FeFe]-hydrogenase
      required for H-H bond formation and cleavage.

PMID- 22394351
TI  - Structural and thermochemical chemisorption of CO2 on Li(4+x)(Si(1-x)Al(x))O4 and
      Li(4-x)(Si(1-x)V(x))O4 solid solutions.
AB  - Different Li(4)SiO(4) solid solutions containing aluminum (Li(4+x)(Si(1
      x)Al(x))O(4)) or vanadium (Li(4-x)(Si(1-x)V(x))O(4)) were prepared by solid state
      reactions. Samples were characterized by X-ray diffraction and solid state
      nuclear magnetic resonance. Then, samples were tested as CO(2) captors.
      Characterization results show that both, aluminum and vanadium ions, occupy
      silicon sites into the Li(4)SiO(4) lattice. Thus, the dissolution of aluminum is
      compensated by Li(1+) interstitials, while the dissolution of vanadium leads to
      lithium vacancies formation. Finally, the CO(2) capture evaluation shows that the
      aluminum presence into the Li(4)SiO(4) structure highly improves the CO(2)
      chemisorption, and on the contrary, vanadium addition inhibits it. The
      differences observed between the CO(2) chemisorption processes are mainly
      correlated to the different lithium secondary phases produced in each case and
      their corresponding diffusion properties.

PMID- 22394352
TI  - Synthesis of disilanyl double-pillared bisdibenzofuran with a high triplet
      energy.
AB  - A double-pillaring strategy for the synthesis of silacyclophanes has been applied
      to dibenzofuran to create a new cyclophane molecule that links two dibenzofuran
      molecules through sigma(SiSi)-pi conjugation. The performance of disilanyl double
      pillared dibenzofuran [(Si)DPBD(O)] in green phosphorescent organic light
      emitting diode (OLED) devices was evaluated as both a carrier-transport material
      and a host material for an Ir-based phosphorescent emitter.

PMID- 22394353
TI  - CYP3A-dependent drug metabolism is reduced in bacterial inflammation in mice.
AB  - BACKGROUND AND PURPOSE: Gene expression of Cyp3a11 is reduced by activation of
      Toll-like receptors (TLRs) by Gram-negative or Gram-positive bacterial
      components, LPS or lipoteichoic acid (LTA) respectively. The primary adaptor
      protein in the TLR signalling pathway, TIRAP, plays differential roles in LPS-
      and LTA-mediated down-regulations of Cyp3a11 mRNA. Here, we have determined the
      functional relevance of these findings by pharmacokinetic/pharmacodynamic (PK/PD)
      analysis of the Cyp3a substrate midazolam in mice. Midazolam is also metabolized
      by Cyp2c in mice. EXPERIMENTAL APPROACH: Adult male C57BL/6, TIRAP+/+ and TIRAP-/
      mice were pretreated with saline, LPS (2 mg.kg-1) or LTA (6 mg.kg-1). Cyp3a11
      protein expression, activity and PK/PD studies using midazolam were performed.
      KEY RESULTS: Cyp3a11 protein expression in LPS- or LTA-treated mice was reduced
      by 95% and 60% compared with saline-treated mice. Cyp3a11 activity was reduced by
      70% in LPS- or LTA-treated mice. Plasma AUC of midazolam was increased two- to
      threefold in LPS- and LTA-treated mice. Plasma levels of 1'-OHMDZ decreased
      significantly only in LTA-treated mice. Both LPS and LTA decreased AUC of 1'
      OHMDZ-glucuronide. In the PD study, sleep time was increased by ~2-fold in LPS-
      and LTA-treated mice. LTA-mediated decrease in Cyp3a11 protein expression and
      activity was dependent on TIRAP. In PK/PD correlation, AUC of midazolam was
      increased only in LPS-treated mice compared with saline-treated mice. CONCLUSIONS
      AND IMPLICATIONS: LPS or LTA altered PK/PD of midazolam. This is the first study
      to demonstrate mechanistic differences in regulation of metabolite formation of a
      clinically relevant drug by Gram-negative or Gram-positive bacterial endotoxins.

PMID- 22394354
TI  - Impaired ocular blood flow regulation in patients with open-angle glaucoma and
      diabetes.
AB  - BACKGROUND:   To elucidate the potential impact of diabetes mellitus on primary
      open-angle glaucoma pathology through vascular deficiency. DESIGN:   Cross
      section analysis from a longitudinal, prospective study. PARTICIPANTS:   Eighty
      four open-angle glaucoma patients (20 diabetic open-angle glaucoma patients and
      64 non-diabetic open-angle glaucoma patients) METHODS:   Patients were analyzed
      for ocular structure, ocular perfusion pressure (OPP), retrobulbar blood flow and
      retinal capillary perfusion. Statistical analysis was performed by SPSS version
      18.0. Comparisons between groups were made as well as multivariate linear
      regression analysis. MAIN OUTCOME MEASURE:   Retrobulbar blood flow and the
      retinal microcirculation. RESULTS:   Central retinal artery peak systolic
      velocity was 13.5% lower in diabetic patients (P = 0.007). In diabetic open-angle
      glaucoma patients, ocular perfusion pressure positively correlated with central
      retinal artery and temporal posterior ciliary artery peak systolic velocity (R =
      0.476, P = 0.039 and R = 0.529, P = 0.02, respectively), and with central retinal
      artery and nasal posterior ciliary artery resistance index (R = 0.537, P = 0.018
      and R = 0.566, P = 0.012 respectively). Average retinal nerve fibre layer
      positively correlated with central retinal artery peak systolic velocity and
      temporal posterior ciliary artery end diastolic velocity (R = 0.501, P = 0.029
      and R = 0.553, P = 0.019, respectively), and negatively correlated with superior
      and inferior retinal avascular space in the diabetic group (R = -0.498, P = 0.030
      and R = -0.700, P = 0.001, respectively); no correlations were found in the non
      diabetic group. Negative correlations between retrobulbar and retinal
      circulations were only found in the diabetic open-angle glaucoma patients,
      whereas positive correlations between retinal flow and non-flow were only found
      in non-diabetic open-angle glaucoma patients. CONCLUSION:   Diabetes may
      interfere with normal vascular regulation and contribute to glaucoma progression.

PMID- 22394355
TI  - Histologic remission of cardiac amyloidosis: a case report.
AB  - The main determinant of survival in amyloid light chain amyloidosis is cardiac
      involvement. The rate of change in wall thickness may be a strong predictor of
      survival. After treatment, some hematologic responders have had documented
      regression of wall thickness by echocardiography with resolution of heart failure
      symptoms. Herein, we demonstrate a case of treated immunoglobulin light chain
      cardiac amyloidosis with echocardiographic wall thinning and cardiac biopsies
      demonstrating complete histologic remission. This observation suggests a
      mechanism of treatment response and that with appropriately timed treatment,
      cardiac deposition of amyloid fibrils can be completely reversed.

PMID- 22394356
TI  - Idiosyncratic reactions and metabolism of sulfur-containing drugs.
AB  - INTRODUCTION: Idiosyncratic drug reactions (IDRs) that involve the formation of
      toxic metabolites followed by covalent binding to cellular proteins often go
      undiscovered until after post-marketing. The goal of this article is to review
      the current status of IDRs, potential mechanisms and the challenges associated
      with predicting drug toxicity. AREAS COVERED: The authors review the metabolic
      pathways of five select classes of sulfur-containing drugs (captopril,
      troglitazone, tienilic acid, zileuton, methimazole and sudoxicam) suggesting that
      bioactivation plays a crucial role in the occurrence of IDRs. The reader will
      gain further awareness that the sulfur atom can propagate as the bioactivation
      site for the formation of reactive and conceivably toxic metabolites. As such, it
      is the body's capacity to detoxify these drug products that may determine whether
      IDRs occur. EXPERT OPINION: Incomplete understanding of mechanisms culminating in
      IDR occurrence represents a monumental impediment toward their abrogation.
      Moreover, current technology utilized to predict their manifestation (including
      structure-toxicity relationships) is not infallible and thus, development of
      novel tools and strategies is indispensible. In an attempt to streamline clinical
      development and drug approval processes, consortiums have been instated under the
      US FDA Critical Path Initiative. Collectively, these parameters along with the
      availability of validated biomarkers and new/updated regulatory guidance could
      positively influence the outcome of drug toxicity profiles and direct future drug
      development.

PMID- 22394357
TI  - Solution structure of Mycobacterium tuberculosis NmtR in the apo state: insights
      into Ni(II)-mediated allostery.
AB  - Mycobacterium tuberculosis is an obligate human respiratory pathogen that encodes
      approximately 10 arsenic repressor (ArsR) family regulatory proteins that allow
      the organism to respond to a wide range of changes in its immediate
      microenvironment. How individual ArsR repressors have evolved to respond to
      selective stimuli is of intrinsic interest. The Ni(II)/Co(II)-specific repressor
      NmtR and related actinomycete nickel sensors harbor a conserved N-terminal alpha
      NH(2)-Gly2-His3-Gly4 sequence. Here, we present the solution structure of
      homodimeric apo-NmtR and show that the core of the molecule adopts a typical
      winged-helix ArsR repressor (alpha1-alpha2-alpha3-alphaR-beta1-beta2-alpha5)
      "open conformation" that is similar to that of the related zinc sensor
      Staphylococcus aureus CzrA, but harboring long, flexible N-terminal (residues 2
      16) and C-terminal (residues 109-120) extensions. Binding of Ni(II) to the
      regulatory sites induces strong paramagnetic broadening of the alpha5 helical
      region and the extreme N-terminal tail to residue 10. Ratiometric pulse chase
      amidination mass spectrometry reveals that the rate of amidination of the alpha
      amino group of Gly2 is strongly attenuated in the Ni(II) complex relative to the
      apo state and noncognate Zn(II) complex. Ni(II) binding also induces dynamic
      disorder on the microsecond to millisecond time scale of key DNA interacting
      regions that likely contributes to the negative regulation of DNA binding by
      Ni(II). Molecular dynamics simulations and quantum chemical calculations reveal
      that NmtR readily accommodates a distal Ni(II) hexacoordination model involving
      the alpha-amine and His3 of the N-terminal region and alpha5 residues Asp91',
      His93', His104, and His107, which collectively define a new metal sensing site
      configuration in ArsR family regulators.

PMID- 22394358
TI  - Prevalence of signs and symptoms of ocular surface disease in individuals treated
      and not treated with glaucoma medication.
AB  - BACKGROUND:   To determine the prevalence of signs and symptoms of ocular surface
      disease in two hospital-based cohorts; glaucoma patients and non-glaucoma
      patients. DESIGN:   A cross-sectional, comparative case series. PARTICIPANTS:  
      Glaucoma patients (n = 300) prescribed topical glaucoma medications for >=6
      months were compared with control patients (n = 100) who were not applying
      prescribed topical medications. METHODS:   A validated self-report questionnaire
      was used to elicit the extent of ocular symptoms. Signs of ocular surface and
      eyelid disease were assessed along with medication history. MAIN OUTCOME
      MEASURES:   Signs and symptoms of ocular surface pathology were determined
      including the tear film break-up time, fluorescein staining of the cornea and
      conjunctiva, meibomian gland dysfunction and Schirmer's test. RESULTS:   A
      significant increase in the prevalence of ocular surface disease signs was
      observed in the glaucoma population, 70.3%, compared with controls, 33% (P <
      0.001). The overall prevalence of clinically significant ocular surface disease
      symptoms was not significantly different between cohorts, 30.7% versus 24.0%,
      respectively (P = 0.252). Logistic regression analysis showed that the number of
      anti-glaucoma medications and duration of therapy were key predictors of
      significant ocular surface disease signs in the glaucoma group. There was no
      significant correlation between signs and symptoms of ocular surface disease in
      either group after adjusting for age and gender. CONCLUSIONS:   Signs and
      symptoms of ocular surface disease are relatively common in older patients, but
      signs of ocular surface disease are significantly higher in individuals who
      instil topical glaucoma therapy.

PMID- 22394359
TI  - Environmental restoration efforts should not make residents struggle for
      survival.

PMID- 22394360
TI  - Nurses, medical records and the killing of sick persons before, during and after
      the Nazi regime in Germany.
AB  - During the Nazi regime (1933-1945), more than 300,000 psychiatric patients were
      killed. The well-calculated killing of chronic mentally 'ill' patients was part
      of a huge biopolitical program of well-established scientific, eugenic standards
      of the time. Among the medical personnel implicated in these assassinations were
      nurses, who carried out this program through their everyday practice. However,
      newer research raises suspicions that psychiatric patients were being
      assassinated before and after the Nazi regime, which, I hypothesize, implies that
      the motives for these killings must be investigated within psychiatric practice
      itself. An investigation of the impact of the interplay between the notes left by
      nurses and those by psychiatrists illustrates the active role of the psychiatric
      medical record in the killing of these patients. Using theoretical insights from
      Michel Foucault and philosopher Giorgio Agamben and analyzing one part of a
      particularly rich patient file found in the Langenhorn Psychiatric Asylum in the
      city of Hamburg, I demonstrate the role of the record in both constructing and
      deconstructing patient subjectivities. De-subjectifying patients condemned them
      to specific zones in the asylum within which they were reduced to their 'bare
      life'--a precondition for their physical assassination.

PMID- 22394361
TI  - Involvement of toll-like receptors in autoimmune sialoadenitis of the non-obese
      diabetic mouse.
AB  - The aim of this study was to characterize the expression of Toll-like receptors
      (TLRs) during the development of sialoadenitis in the non-obese diabetic mouse.
      Submandibular glands were dissected from non-obese diabetic mice at 4, 8, 10, 12,
      and 16 weeks of age. The mRNA expression levels of TLR1, 2, 3, 4, 5, 6, 7, 8, 9,
      11, 12, 13, MyD88, and TRIF was quantified using real-time reverse transcription
      polymerase chain reaction. The mRNA expression levels in 4-week-old non-obese
      diabetic mice were used as controls. The expression levels of TLR1, 2, 4, and 9
      were significantly higher at 8, 10, 12, and 16 weeks than the levels in the
      controls. The expression level of TLR3 was significantly higher at 16 weeks than
      in the controls. A group of mice were given drinking water containing 4.75%
      chloroquine starting at 4 weeks. Chloroquine caused a significant decrease in the
      expression of TLR1, 2, 3, 4, and 9 at 16 weeks compared with control mice who did
      not receive chloroquine. The areas of lymphocyte infiltration seen on serial
      sections of submandibular glands in the mice receiving chloroquine were
      significantly smaller than the areas of infiltration in control glands. Increased
      expression of Toll-like receptors may be involved in the development and/or
      progression of sialoadenitis in the non-obese diabetic mouse. Toll-like receptors
      may be a therapeutic target for autoimmune sialoadenitis.

PMID- 22394362
TI  - Nanoengineering strategies for metal-insulator-metal electrostatic
      nanocapacitors.
AB  - Nanostructures can improve the performance of electrical energy storage devices.
      Recently, metal-insulator-metal (MIM) electrostatic capacitors fabricated in a
      three-dimensional cylindrical nanotemplate of anodized aluminum oxide (AAO)
      porous film have shown profound increase in device capacitance (100* or more)
      over planar structures. However, inherent asperities at the top of the
      nanostructure template cause locally high field strengths and lead to low
      breakdown voltage. This severely limits the usable voltage, the associated energy
      density (1/2 CV(2)), and thus the operational charge-discharge window of the
      device. We describe an electrochemical technique, complementary to the self
      assembled template pore formation process in the AAO film, that provides
      nanoengineered topographies with significantly reduced local electric field
      concentrations, enabling breakdown fields up to 2.5* higher (to >10 MV/cm) while
      reducing leakage current densities by 1 order of magnitude (to ~10(-10) A/cm(2)).
      In addition, we consider and optimize the AAO template and nanopore dimensions,
      increasing the capacitance per planar unit area by another 20%. As a result, the
      MIM nanocapacitor devices achieve an energy density of ~1.5 Wh/kg--the highest
      reported.

PMID- 22394364
TI  - Facile activation of H-H and Si-H bonds by boranes.
AB  - The borane B(C(6)F(5))(3) is a precatalyst for H/Dexchange between H(2) and
      deuterium-labeled silanes (D(3)SiPh, D(2)SiMePh, DSiMe(2)Ph, DSiEt(3)).
      Experimental and DFT studies reveal that B(C(6)F(5))(3) itself cannot activate
      dihydrogen but converts to HB(C(6)F(5))(2) under the action of hydrosilane. The
      latter species easily activates H-H and Si-H bonds by a sigma-bond metathesis
      mechanism, which was further confirmed by the reactions of BD(3).THF with H(2).

PMID- 22394363
TI  - EGFR overexpression relates to triple negative profile and poor prognosis in
      breast cancer patients in Tunisia.
AB  - BACKGROUND: The prognosis of breast carcinoma is related to a large variety of
      clinical and pathological factors. Currently, only oestrogen (ER) and
      progesterone (PR) receptors and human epidermal growth factor receptor 2 (HER2)
      are used in routine pathological assessment as biomarkers. The aim of this study
      was to evaluate the prognostic impact of epidermal growth factor receptor (EGFR)
      expression individually and in combination to classical biomarkers (HER2, ER, and
      PR), and its relation to tumors with triple negative profile in Tunisian breast
      carcinoma. METHODS: Immunohistochemistry was used to estimate the rate expression
      of these receptors. Univariate and multivariate analyses were used to explore the
      prognostic significance of EGFR in this study. RESULTS: The expression rate of
      EGFR was 28.6%. EGFR expression was inversely correlated to that of ER (P <
      0.001). Significant correlations between the expression of EGFR and the high
      histological Scarff-Bloom-Richardson (SBR) grade (P = 0.038) and also with tumors
      size (P = 0.041) were observed. The triple negative profile (TN: ER-/PR-/HER2-)
      was present in 17.3% of cases. EGFR overexpression was positively associated with
      this clinical aggressive profile (P < 0.001). Survival analysis showed that EGFR
      expression was associated with poor survival of patients (P = 0.004). In
      multivariate analysis, EGFR expression (P = 0.035) was found to be independent
      prognostic factors (significantly correlated to survival). CONCLUSION: EGFR
      overexpression was observed in 28.6% of Tunisian breast carcinoma, associated
      with unfavorable prognosis and with triple negative tumors. Systemically
      evaluation of EGFR in breast carcinoma could benefit especially to TN subgroup
      from EGFR targeting agents.

PMID- 22394365
TI  - Characteristics of palliative care consultation services in California hospitals.
AB  - BACKGROUND: Although hospital palliative care consultation services (PCCS) can
      improve a variety of clinical and nonclinical outcomes, little is known about how
      these services are structured. METHODS: We surveyed all 351 acute care hospitals
      in California to examine the structure and characteristics of those hospitals
      with PCCS. RESULTS: We achieved a 92% response rate. Thirty-one percent (n=107)
      of hospitals reported having a PCCS. Teams commonly included physicians (87%),
      social workers (80%), spiritual care professionals (77%), and registered nurses
      (71%). Nearly all PCCS were available on-site during weekday business hours; 50%
      were available on-site or by phone in the weekday evenings and 54% were available
      during weekend daytime hours. The PCCS saw an average of 347 patients annually
      (median=310, standard deviation [SD]=217), or 258 patients per clinical full-time
      equivalent (FTE; median=250, SD=150.3). Overall, 60% of consultation services
      reported they are struggling to cope with the workload. On average, patients were
      in the hospital 5.9 days (median=5.5, SD=3.3) prior to referral to PCCS, and
      remained in the hospital for 6 days (median=4, SD=7.9) following the initial
      consultation. Patient and family meetings were an aspect of the consultation in
      74% of cases. Overall, 21% of consultation patients were discharged home with
      hospice services and 25% died in the hospital. CONCLUSIONS: There is variation in
      how PCCS in California hospitals are structured and in the ways they engage with
      patients. Ultimately, linking PCCS characteristics and practices to patient and
      family outcomes will identify best practices that PCCS can use to maximize
      quality.

PMID- 22394366
TI  - Epoprostenol use for pulmonary arterial hypertension in the palliative care
      setting.
AB  - Prostacyclin analogues such as epoprostenol (Flolan(r)) are commonly used in the
      treatment of pulmonary arterial hypertension (PAH). However, their complex
      administration and significant cost may limit the access that patients with PAH
      have to palliative and hospice care. We herein report our experience using
      epoprostenol in a dedicated palliative care unit and present our inpatient
      protocol for the drug's administration.

PMID- 22394367
TI  - Diastereoselective protocols for the synthesis of 2,3-trans- and 2,3-cis-6
      methoxy-morpholine-2-carboxylic acid derivatives.
AB  - Two diastereoselective and straightforward protocols for the high-yielding
      synthesis of 2,3-trans- and 2,3-cis-6-methoxy-3-substituted morpholine-2
      carboxylic esters were realized in few steps, through the condensation between
      5,6-diethoxy-5,6-dimethyl-1,4-dioxan-2-one and an appropriate imine, which is the
      key reaction to control the C2-C3 relative stereochemistry, followed by a
      methanolysis/ring-closure tandem reaction sequence. In particular, 2,3-trans
      morpholines derive from the R*,S*-product of the acid condensation of N
      functionalized alkylimines with the silylketene acetal of the above lactone,
      whereas 2,3-cis-morpholines derive from the R*,R*-product of basic condensation
      of an N-tosylimines with the lactone.

PMID- 22394368
TI  - Immunocombination therapy for high-risk neuroblastoma.
AB  - Neuroblastoma (NBL) is an aggressive malignancy of the sympathetic nervous
      system. Advanced-stage NBLs prove fatal in approximately 50% of patients within 5
      years. Therefore, new treatment modalities are urgently needed. Immunotherapy is
      a treatment modality that can be combined with established forms of treatment.
      Administration of monoclonal antibodies or dendritic cell-based therapies alone
      can lead to favorable clinical outcomes in individual cancer patients; for
      example patients with melanoma, lymphoma and NBL. However, clinical benefit is
      still limited to a minority of patients, and further improvements are clearly
      needed. In this article, we review the most commonly used approaches to treat
      patients with NBL and highlight the prerequisites and opportunities of cell-based
      immunotherapy, involving both innate and adaptive immune-effector cells.
      Furthermore, we discuss the potential of the combined application of
      immunotherapy and novel tumor-targeted therapies for the treatment of both cancer
      in general and NBL in particular.

PMID- 22394369
TI  - In vivo toxicity evaluation of gold-dendrimer composite nanodevices with
      different surface charges.
AB  - Composite nanodevices (CNDs) are multifunctional nanomaterials with potential
      uses in cancer imaging and therapy. Poly(amidoamine) dendrimer-based composite
      nanodevices are important members of this group and consist of an organic
      dendrimer component and an incorporated inorganic component, in this case, gold.
      This study addresses the short- (14 days) and long-term (78 days) in vivo
      toxicity of generation-5 (G5; 5 nm) PAMAM dendrimer-based gold-CNDs (Au-CNDs)
      with varying surface charges (positive, negative and neutral) in C57BL/6J male
      mice. Detailed toxicological analyses of (1) body weight changes, (2) serum
      chemistry and (3) histopathological examination of 22 organs showed no evidence
      of organ injury or organ function compromise. Zeta potential of Au-CNDs showed
      significant change from their parent dendrimers upon gold incorporation, making
      the normally lethal positive surface dendrimer biologically safe. Also
      homeostatic mechanisms in vivo may compensate/repair toxic effects, something not
      seen with in vitro assays.

PMID- 22394370
TI  - Evaluation of cut-off saw exposure control methods for respirable dust and
      crystalline silica in roadway construction.
AB  - Dust reduction equipment adapted for single-person operation was evaluated for
      gas-powered, commercially available cut-off saws during concrete curb cutting.
      Cutting was performed without dust control and with two individual exposure
      control methods: wet suppression and local exhaust ventilation (LEV). The wet
      suppression system comprised a two-nozzle spray system and a 13.3-L hand
      pressurized water supply system with an optimum mean flow rate of 0.83 L/min for
      16 min of cutting. The LEV system consisted of a spring-loaded guard, an 18.9-L
      collection bag, and a centrifugal fan with an estimated exhaust rate of 91
      ft(3)/min. Task-based, personal filter samples were obtained for four saw
      operators during cutting durations of 4 to 16 min on five job sites. Seventeen
      filter samples were collected without dust control, 14 with wet suppression, and
      12 with LEV, yielding a geometric mean respirable dust concentration of 16.4
      mg/m(3), 3.60 mg/m(3), and 4.40 mg/m(3), respectively. A dust reduction of 78.0%
      for wet suppression and 73.2% for LEV was observed vs. no dust control. A
      statistically significant difference (p < 0.001) was also revealed for wet
      suppression and LEV when compared with no dust control; however, a significant
      difference (p = 0.09) was not observed between wet suppression and LEV. Despite
      these significant dust reductions, workers are still projected to exceed the
      ACGIH 8-hr time-weighted average threshold limit value for quartz (0.025 mg/m(3))
      in less than 1 hr of cutting for both dust control methods. Further research is
      still needed to improve dust reduction and portability of both control methods,
      but the current LEV system offers important advantages, including a drier, less
      slippery work area and year-round functionality in cold weather.

PMID- 22394371
TI  - Activating PDGFRA mutations in inflammatory fibroid polyps occur in exons 12, 14
      and 18 and are associated with tumour localization.
AB  - AIMS: Inflammatory fibroid polyps (IFP) are mesenchymal tumours of the
      gastrointestinal tract. This study was performed to broaden the base of evidence
      of the pathogenic role of PDGFR mutations in IFP with particular regard to
      clinicopathological data and mutational patterns among IFP subtypes. METHODS AND
      RESULTS: Molecular analysis of 38 tumours revealed activating mutations in three
      different exons of PDGFRA in 25 IFP. For the first time we report two cases with
      PDGFRA-exon 14 mutations (p.N659K; p.[N659K(+)T665A]). The results of our study
      and cases reported earlier indicate clearly that there is a localization-specific
      pattern: exon 12 mutations predominate in the small intestine, while exon 18
      mutations occur frequently in the stomach (P < 0.001). Codons 567-571 of PDGFRA
      represent an IFP specific mutational hot spot and are affected most frequently by
      deletions. Furthermore, in our series IFP of the stomach share common features.
      In contrast to intestinal IFP, gastric tumours occur at higher age, show heavy
      inflammation and tend to be smaller. IFP located in the small intestine are
      frequently associated with intussusception. CONCLUSION: We conclude that there is
      a 'small bowel' and a 'gastric' phenotype of IFPs which are associated with exon
      12 and exon 18 PDGFRA mutations, respectively.

PMID- 22394372
TI  - Investigating the mechanism of phenol photooxidation by humic substances.
AB  - To probe the mechanism of the photosensitized loss of phenols by humic substances
      (HS), the dependence of the initial rate of 2,4,6-trimethylphenol (TMP) loss
      (R(TMP)) on dioxygen concentration was examined both for a variety of untreated
      as well as borohydride-reduced HS and C(18) extracts from the Delaware Bay and
      Mid-Atlantic Bight. R(TMP) was inversely proportional to dioxygen concentration
      at [O(2)] > 50 MUM, a dependence consistent with reaction with triplet excited
      states, but not with (1)O(2) or RO(2). Modeling the dependence of R(TMP) on
      [O(2)] provided rate constants for TMP reaction, O(2) quenching, and lifetimes
      compatible with a triplet intermediate. Borohydride reduction significantly
      reduced TMP loss, supporting the role of aromatic ketone triplets in this
      process. However, for most samples, the incomplete loss of sensitization
      following borohydride reduction, as well as the inverse dependence of R(TMP) on
      [O(2)] for these samples, suggests that there remains another class of oxidizing
      triplet sensitizer, perhaps quinones.

PMID- 22394373
TI  - Ablation of MMP9 induces survival and differentiation of cardiac stem cells into
      cardiomyocytes in the heart of diabetics: a role of extracellular matrix.
AB  - The contribution of extracellular matrix (ECM) to stem cell survival and
      differentiation is unequivocal, and matrix metalloproteinase-9 (MMP9) induces ECM
      turn over; however, the role of MMP9 in the survival and differentiation of
      cardiac stem cells is unclear. We hypothesize that ablation of MMP9 enhances the
      survival and differentiation of cardiac stem cells into cardiomyocytes in
      diabetics. To test our hypothesis, Ins2(+/-) Akita, C57 BL/6J, and double knock
      out (DKO: Ins2(+/-)/MMP9(-/-)) mice were used. We created the DKO mice by
      deleting the MMP9 gene from Ins2(+/-). The above 3 groups of mice were genotyped.
      The activity and expression of MMP9 in the 3 groups were determined by in-gel
      gelatin zymography, Western blotting, and confocal microscopy. To determine the
      role of MMP9 in ECM stiffness (fibrosis), we measured collagen deposition in the
      histological sections of hearts using Masson's trichrome staining. The role of
      MMP9 in cardiac stem cell survival and differentiation was determined by co
      immunoprecipitation (co-IP) of MMP9 with c-kit (a marker of stem cells) and
      measuring the level of troponin I (a marker of cardiomyocytes) by confocal
      microscopy in the 3 groups. Our results revealed that ablation of MMP9 (i)
      reduces the stiffness of ECM by decreasing collagen accumulation (fibrosis), and
      (ii) enhances the survival (elevated c-kit level) and differentiation of cardiac
      stem cells into cardiomyocytes (increased troponin I) in diabetes. We conclude
      that inhibition of MMP9 ameliorates stem cell survival and their differentiation
      into cardiomyocytes in diabetes.

PMID- 22394374
TI  - Sex differences in brain proteomes of neuron-specific STAT3-null mice after
      cerebral ischemia/reperfusion.
AB  - Signal transduction and activator of transcription-3 (STAT3) plays an important
      role in neuronal survival, regeneration and repair after brain injury. We
      previously demonstrated that STAT3 is activated in brain after cerebral ischemia
      specifically in neurons. The effect was sex-specific and modulated by sex
      steroids, with higher activation in females than males. In the current study, we
      used a proteomics approach to identify downstream proteins affected by ischemia
      in male and female wild-type (WT) and neuron-specific STAT3 knockout (KO) mice.
      We established four comparison groups based on the transgenic condition and the
      hemisphere analyzed, respectively. Moreover, the sexual variable was taken into
      account and male and female animals were analyzed independently. Results support
      a role for STAT3 in metabolic, synaptic, structural and transcriptional responses
      to cerebral ischemia, indeed the adaptive response to ischemia/reperfusion injury
      is delayed in neuronal-specific STAT3 KO mice. The differences observed between
      males and females emphasize the importance of sex-specific neuronal survival and
      repair mechanisms, especially those involving antioxidant and energy-related
      activities, often caused by sex hormones.

PMID- 22394375
TI  - Towards deciphering dynamic changes and evolutionary mechanisms involved in the
      adaptation to low salinities in Ectocarpus (brown algae).
AB  - Colonizations of freshwater by marine species are rare events, and little
      information is known about the underlying mechanisms. Brown algae are an
      independent lineage of photosynthetic and multicellular organisms from which few
      species inhabit freshwater. As a marine alga that is also found in freshwater,
      Ectocarpus is of particular interest for studying the transition between these
      habitats. To gain insights into mechanisms of the transition, we examined
      salinity tolerance and adaptations to low salinities in a freshwater strain of
      Ectocarpus on physiological and molecular levels. We show that this isolate
      belongs to a widely distributed and highly stress-resistant clade, and differed
      from the genome-sequenced marine strain in its tolerance of low salinities. It
      also exhibited profound, but reversible, morphological, physiological, and
      transcriptomic changes when transferred to seawater. Although gene expression
      profiles were similar in both strains under identical conditions, metabolite and
      ion profiles differed strongly, the freshwater strain exhibiting e.g. higher
      cellular contents of amino acids and nitrate, higher contents of n-3 fatty acids,
      and lower intracellular mannitol and sodium concentrations. Moreover, several
      stress markers were noted in the freshwater isolate in seawater. This finding
      suggests that, while high stress tolerance and plasticity may be prerequisites
      for the colonization of freshwater, genomic alterations have occurred that
      produced permanent changes in the metabolite profiles to stabilize the
      transition.

PMID- 22394377
TI  - Ketamine uropathy: rising to the challenges of a new condition.

PMID- 22394376
TI  - Rosiglitazone selectively inhibits K(ATP)  channels by acting on the K(IR) 6
      subunit.
AB  - BACKGROUND AND PURPOSE: Rosiglitazone is an anti-diabetic drug acting as an
      insulin sensitizer. We recently found that rosiglitazone also inhibits the
      vascular isoform of ATP-sensitive K(+) channels and compromises vasodilatory
      effects of beta-adrenoceptor activation and pinacidil. As its potency for the
      channel inhibition is in the micromolar range, rosiglitazone may be used as an
      effective K(ATP) channel inhibitor for research and therapeutic purposes.
      Therefore, we performed experiments to determine whether other isoforms of K(ATP)
      channels are also sensitive to rosiglitazone and what their sensitivities are.
      EXPERIMENTAL APPROACH: K(IR) 6.1/SUR2B, K(IR) 6.2/SUR1, K(IR) 6.2/SUR2A, K(IR)
      6.2/SUR2B and K(IR) 6.2DeltaC36 channels were expressed in HEK293 cells and were
      studied using patch-clamp techniques. KEY RESULTS: Rosiglitazone inhibited all
      isoforms of K(ATP) channels in excised patches and in the whole-cell
      configuration. Its IC(50) was 10 umol.L(-1) for the K(IR) 6.1/SUR2B channel and
      ~45 umol.L(-1) for K(IR) 6.2/SURx channels. Rosiglitazone also inhibited K(IR)
      6.2DeltaC36 channels in the absence of the sulphonylurea receptor (SUR) subunit,
      with potency (IC(50) = 45 umol.L(-1) ) almost identical to that for K(IR)
      6.2/SURx channels. Single-channel kinetic analysis showed that the channel
      inhibition was mediated by augmentation of the long-lasting closures without
      affecting the channel open state and unitary conductance. In contrast,
      rosiglitazone had no effect on K(IR) 1.1, K(IR) 2.1 and K(IR) 4.1 channels,
      suggesting that the channel inhibitory effect is selective for K(IR) 6.x
      channels. CONCLUSIONS AND IMPLICATIONS: These results suggest a novel K(ATP)
      channel inhibitor that acts on the pore-forming K(IR) 6.x subunit, affecting the
      channel gating.

PMID- 22394378
TI  - Screening for depression: integrating training into the professional development
      programme for low vision rehabilitation staff.
AB  - BACKGROUND: To describe the integration of depression screening training into the
      professional development programme for low vision rehabilitation staff and report
      on staff evaluation of this training. DESIGN: Pre-post intervention study, in a
      single population of low vision rehabilitation staff. PARTICIPANTS: Three hundred
      and thirty-six staff from Australia's largest low vision rehabilitation
      organization, Vision Australia. METHODS: Staff completed the depression screening
      and referral training as part of a wider professional development programme. A
      pre-post-training questionnaire was administered to all staff. MAIN OUTCOME
      MEASURES: Descriptive and non-parametric statistics were used to determine
      differences in self-reported knowledge, confidence, barriers to recognition and
      management of depression between baseline and post training. RESULTS: One hundred
      and seventy-two participants completed both questionnaires. Following training,
      participants reported an increased knowledge of depression, were more likely to
      respond to depression in their clients and reported to be more confident in
      managing depression (P < 0.05). A range of barriers were identified including
      issues related to the client (e.g. acceptance of referrals); practitioners (e.g.
      skill, role); availability and accessibility of psychological services; time and
      contact constraints; and environmental barriers (e.g. lack of privacy).
      Additional training incorporating more active and 'hands-on' sessions are likely
      to be required. CONCLUSIONS: This training is a promising first step in
      integrating a depression screening tool into low vision rehabilitation practice.
      Further work is needed to determine the barriers and facilitators to
      implementation in practice and to assess clients' acceptability and outcomes.

PMID- 22394380
TI  - Shock tube explorations of roaming radical mechanisms: the decompositions of
      isobutane and neopentane.
AB  - The thermal decompositions of isobutane and neopentane have been studied using
      both shock tube experiments and ab initio transition state theory based master
      equation calculations. Dissociation rate constants for these molecules have been
      measured at high temperatures (1260-1566 K) behind reflected shock waves using
      high-sensitivity H-ARAS detection. The two major dissociation channels at high
      temperature are iso-C(4)H(10) -> CH(3) + i-C(3)H(7) (1a) and neo-C(5)H(12) ->
      CH(3) + t-C(4)H(9) (2a). Ultrahigh-sensitivity ARAS detection of H-atoms produced
      from the rapid decomposition of the product radicals, i-C(3)H(7) in (1a) and t
      C(4)H(9) in (2a), through i-C(3)H(7) + M -> H + C(3)H(6) + M (3a) and t-C(4)H(9)
      + M -> H + i-C(4)H(8) + M (4a) allowed measurements of both the total
      decomposition rate constants, k(total), and the branching to radical products,
      which were observed to be equivalent in both systems, k(1a)/k(total) and
      k(2a)/k(total) = 0.79 +/- 0.05. Theoretical analyses indicate that in isobutane,
      the non-H-atom fraction has two contributions, the dominant fraction being due to
      the roaming radical mechanism leading to molecular products through iso-C(4)H(10)
      -> CH(4) + C(3)H(6) (1b) with k(1b)/k(total) = 0.16, and a minor fraction that
      involves the isomerization of i-C(3)H(7) to n-C(3)H(7) that then subsequently
      forms methyl radicals, i-C(3)H(7) + M -> n-C(3)H(7) + M -> CH(3) + C(2)H(4) + M
      (3b). In contrast to isobutane, in neopentane, the contribution to the non-H-atom
      fraction is exclusively through the roaming radical mechanism that leads to neo
      C(5)H(12) -> CH(4) + i-C(4)H(8) (2b) with k(2b)/k(total) = 0.21. These
      quantitative measurements of larger contributions from the roaming mechanism for
      larger molecules are in agreement with the qualitative theoretical arguments that
      suggest long-range dispersion interactions (which become increasingly important
      for larger molecules) may enhance roaming.

PMID- 22394379
TI  - Bupropion binds to two sites in the Torpedo nicotinic acetylcholine receptor
      transmembrane domain: a photoaffinity labeling study with the bupropion analogue
      [(125)I]-SADU-3-72.
AB  - Bupropion, a clinically used antidepressant and smoking-cessation drug, acts as a
      noncompetitive antagonist of nicotinic acetylcholine receptors (nAChRs). To
      identify its binding site(s) in nAChRs, we developed a photoreactive bupropion
      analogue, (+/-)-2-(N-tert-butylamino)-3'-[(125)I]-iodo-4'-azidopropiophenone
      (SADU-3-72). Based on inhibition of [(125)I]SADU-3-72 binding, SADU-3-72 binds
      with high affinity (IC(50) = 0.8 MUM) to the Torpedo nAChR in the resting (closed
      channel) state and in the agonist-induced desensitized state, and bupropion binds
      to that site with 3-fold higher affinity in the desensitized (IC(50) = 1.2 MUM)
      than in the resting state. Photolabeling of Torpedo nAChRs with [(125)I]SADU-3-72
      followed by limited in-gel digestion of nAChR subunits with endoproteinase Glu-C
      established the presence of [(125)I]SADU-3-72 photoincorporation within nAChR
      subunit fragments containing M1-M2-M3 helices (alphaV8-20K, betaV8-22/23K, and
      gammaV8-24K) or M1-M2 helices (deltaV8-14). Photolabeling within betaV8-22/23K,
      gammaV8-24K, and deltaV8-14 was reduced in the desensitized state and inhibited
      by ion channel blockers selective for the resting (tetracaine) or desensitized
      (thienycyclohexylpiperidine (TCP)) state, and this pharmacologically specific
      photolabeling was localized to the M2-9 leucine ring (deltaLeu(265),
      betaLeu(257)) within the ion channel. In contrast, photolabeling within the
      alphaV8-20K was enhanced in the desensitized state and not inhibited by TCP but
      was inhibited by bupropion. This agonist-enhanced photolabeling was localized to
      alphaTyr(213) in alphaM1. These results establish the presence of two distinct
      bupropion binding sites within the Torpedo nAChR transmembrane domain: a high
      affinity site at the middle (M2-9) of the ion channel and a second site near the
      extracellular end of alphaM1 within a previously described halothane (general
      anesthetic) binding pocket.

PMID- 22394381
TI  - Diverging pathways to topologically complex polycyclic bis-acetals and their ring
      system interchange.
AB  - Carbinol-tethered octalin-diols (1), which differ only by the C11 configuration
      at the angular position, were transformed selectively to three types of
      structurally unrelated original scaffolds such as unsymmetrical
      octahydroanthracenes (5/7), furofuranes (6), or spirans (8/9) via a two-step
      protocol. The 11S* configuration ensures a C13-C4 Friedel-Crafts type C-C bonding
      (through an unprecedented oxidative cleavage-triggered domino process) while the
      11R* configuration allows for a C13-C2 Marson-type Friedel-Crafts C-C bonding
      (through a nucleophilic acetal opening).

PMID- 22394382
TI  - Plant DNA barcodes and the influence of gene flow.
AB  - Success of species assignment using DNA barcodes has been shown to vary among
      plant lineages because of a wide range of different factors. In this study, we
      confirm the theoretical prediction that gene flow influences species assignment
      with simulations and a literature survey. We show that the genome experiencing
      the highest gene flow is, in the majority of the cases, the best suited for
      species delimitation. Our results clearly suggest that, for most angiosperm
      groups, plastid markers will not be the most appropriate for use as DNA barcodes.
      We therefore advocate shifting the focus from plastid to nuclear markers to
      achieve an overall higher success using DNA barcodes.

PMID- 22394383
TI  - Comparison of optic nerve head parameters using Heidelberg Retina Tomograph 3 and
      spectral-domain optical coherence tomography.
AB  - BACKGROUND:   To assess the agreement between the Heidelberg Retina Tomograph and
      Cirrus spectral-domain optical coherence tomography (Cirrus HD-OCT [Carl Zeiss
      Meditec, Dublin, CA, USA]) when measuring optic disc parameters. DESIGN:  
      Prospective, cross-sectional study. PARTICIPANTS:   A total of 96 glaucoma
      patients and 21 normal subjects were analysed. METHODS:   Optic nerve head
      measurements, including disc area, rim area, cup-to-disc ratio and cup volume
      were obtained using both the Cirrus HD-OCT and Heidelberg Retina Tomograph 3
      (Heidelberg Engineering GmbH, Heidelberg, Germany). MAIN OUTCOME MEASUREMENTS:  
      Bland-Altman plots were used to evaluate the agreement between each of the optic
      disc parameters. RESULTS:   Although Cirrus HD-OCT values were smaller than
      Heidelberg Retina Tomograph 3 values for the disc and rim areas, overall the
      Cirrus HD-OCT and Heidelberg Retina Tomograph 3 measurements were highly
      correlated (r = 0.657 to 0.821). As compared with Heidelberg Retina Tomograph 3,
      disc and rim areas tended to be minimized by Cirrus HD-OCT, especially when there
      were large disc and rim areas, although there was no relationship between the
      discrepancy and the level of measurement of the cup-to-disc ratio. The optical
      coherence tomography overestimated the Heidelberg Retina Tomograph-determined cup
      volume, especially when there were large cup volumes. CONCLUSIONS:   Bland-Altman
      analyses revealed that with the exception of the cup-to-disc ratio, there was
      poor agreement between the Cirrus HD-OCT and Heidelberg Retina Tomograph 3
      morphometric measurements. In addition, with the exception of the cup-to-disc
      ratio, the optic nerve head measurements could not be directly compared between
      the Cirrus HD-OCT and Heidelberg Retina Tomograph 3.

PMID- 22394385
TI  - Abstracts of the Thoracic Society of Australia & New Zealand and the Australian &
      New Zealand Society of Respiratory Science 2012 Annual Scientific Meetings. March
      30-April 4, 2012. Canberra, ACT, Australia.

PMID- 22394384
TI  - The cytokine tumor necrosis factor-like weak inducer of apoptosis and its
      receptor fibroblast growth factor-inducible 14 have a neuroprotective effect in
      the central nervous system.
AB  - BACKGROUND: Cerebral cortical neurons have a high vulnerability to the harmful
      effects of hypoxia. However, the brain has the ability to detect and accommodate
      to hypoxic conditions. This phenomenon, known as preconditioning, is a natural
      adaptive process highly preserved among species whereby exposure to sub-lethal
      hypoxia promotes the acquisition of tolerance to a subsequent lethal hypoxic
      injury. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK)
      and its receptor fibroblast growth factor-inducible 14 (Fn14) are found in
      neurons and their expression is induced by exposure to sub-lethal hypoxia.
      Accordingly, in this work we tested the hypothesis that the interaction between
      TWEAK and Fn14 induces tolerance to lethal hypoxic and ischemic conditions.
      METHODS: Here we used in vitro and in vivo models of hypoxic and ischemic
      preconditioning, an animal model of transient middle cerebral artery occlusion
      and mice and neurons genetically deficient in TWEAK, Fn14, or tumor necrosis
      factor alpha (TNF-alpha) to investigate whether treatment with recombinant TWEAK
      or an increase in the expression of endogenous TWEAK renders neurons tolerant to
      lethal hypoxia. We used enzyme-linked immunosorbent assay to study the effect of
      TWEAK on the expression of neuronal TNF-alpha, Western blot analysis to
      investigate whether the effect of TWEAK was mediated by activation of mitogen
      activated protein kinases and immunohistochemical techniques and quantitative
      real-time polymerase chain reaction analysis to study the effect of TWEAK on
      apoptotic cell death. RESULTS: We found that either treatment with recombinant
      TWEAK or an increase in the expression of TWEAK and Fn14 induce hypoxic and
      ischemic tolerance in vivo and in vitro. This protective effect is mediated by
      neuronal TNF-alpha and activation of the extracellular signal-regulated kinases 1
      and 2 pathway via phosphorylation and inactivation of the B-cell lymphoma 2
      associated death promoter protein. CONCLUSIONS: Our work indicate that the
      interaction between TWEAK and Fn14 triggers the activation of a cell signaling
      pathway that results in the induction of tolerance to lethal hypoxia and
      ischemia. These data indicate that TWEAK may be a potential therapeutic strategy
      to protect the brain from the devastating effects of an ischemic injury.

PMID- 22394386
TI  - Population-based tobacco treatment: study design of a randomized controlled
      trial.
AB  - BACKGROUND: Most smokers do not receive comprehensive, evidence-based treatment
      for tobacco use that includes intensive behavioral counseling along with
      pharmacotherapy. Further, the use of proven, tobacco treatments is lower among
      minorities than among Whites. The primary objectives of this study are to: (1)
      Assess the effect of a proactive care intervention (PRO) on population-level
      smoking abstinence rates (i.e., abstinence among all smokers including those who
      use and do not utilize treatment) and on utilization of tobacco treatment
      compared to reactive/usual care (UC) among a diverse population of smokers, (2)
      Compare the effect of PRO on population-level smoking abstinence rates and
      utilization of tobacco treatments between African American and White smokers, and
      (3) Determine the cost-effectiveness of the proactive care intervention.
      METHODS/DESIGN: This prospective randomized controlled trial identifies a
      population-based sample of current smokers from the Department of Veterans
      Affairs (VA) electronic medical record health factor dataset. The proactive care
      intervention combines: (1) proactive outreach and (2) offer of choice of smoking
      cessation services (telephone or face-to-face). Proactive outreach includes
      mailed invitation materials followed by an outreach call that encourages smokers
      to seek treatment with choice of services. Proactive care participants who choose
      telephone care receive VA telephone counseling and access to pharmacotherapy.
      Proactive care participants who choose face-to-face care are referred to their VA
      facility's smoking cessation clinic. Usual care participants have access to
      standard smoking cessation services from their VA facility (e.g.,
      pharmacotherapy, smoking cessation clinic) and from their state telephone
      quitline. Baseline data is collected from VA administrative databases and
      participant surveys. Outcomes from both groups are collected 12 months post
      randomization from participant surveys and from VA administrative databases. The
      primary outcome is self-reported smoking abstinence, which is assessed at the
      population-level (i.e., among those who utilize and those who do not utilize
      tobacco treatment). Primary analyses will follow intention-to-treat methodology.
      DISCUSSION: This randomized trial is testing proactive outreach strategies
      offering choice of smoking cessation services, an innovation that if proven
      effective and cost-effective, will transform the way tobacco treatment is
      delivered. National dissemination of proactive treatment strategies could
      dramatically reduce tobacco-related morbidity, mortality, and health care costs.
      CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov: NCT00608426.

PMID- 22394387
TI  - Prevalence of Ancylostoma braziliense in dogs from Alachua and Marion Counties,
      Florida, United States.
AB  - A convenience collection of fecal samples from 148 dogs in northern Florida was
      examined for the presence of Ancylostoma braziliense eggs by using centrifugal
      sugar flotation and polymerase chain reaction (PCR)-restriction fragment length
      polymorphism (RFLP). Of the 148 samples, 64 (43.2%) contained hookworm eggs. DNA
      from 42 samples was successfully amplified using PCR; using RFLP, 2 samples were
      identified as containing DNA of A. braziliense (4.8% of the 42 successfully
      amplified samples).

PMID- 22394388
TI  - How does selfing affect the dynamics of selfish transposable elements?
AB  - BACKGROUND: Many theoretical models predicting the dynamics of transposable
      elements (TEs) in genomes, populations, and species have already been proposed.
      However, most of them only focus on populations of sexual diploid individuals,
      and TE dynamics in populations partly composed by autogamous individuals remains
      poorly investigated. To estimate the impact of selfing on TE dynamics, the short-
      and long-term evolution of TEs was simulated in outcrossing populations with
      various proportions of selfing individuals. RESULTS: Selfing has a deep impact on
      TE dynamics: the higher the selfing rate, the lower the probability of invasion.
      Already known non-equilibrium dynamics (complete loss, domestication, cyclical
      invasion of TEs) can all be described whatever the mating system. However, their
      pattern and their respective frequencies greatly depend on the selfing rate. For
      instance, in cyclical dynamics resulting from interactions between autonomous and
      non-autonomous copies, cycles are faster when the selfing rate increases.
      Interestingly, an abrupt change in the mating system from sexuality to complete
      asexuality leads to the loss of all the elements over a few hundred generations.
      In general, for intermediate selfing rates, the transposition activity remains
      maintained. CONCLUSIONS: Our theoretical results evidence that a clear and
      systematic contrast in TE content according to the mating system is expected,
      with a smooth transition for intermediate selfing rates. Several parameters
      impact the TE copy number, and all dynamics described in allogamous populations
      can be also observed in partly autogamous species. This study thus provides new
      insights to understand the complex signal from empirical comparison of closely
      related species with different mating systems.

PMID- 22394389
TI  - Three-component glycolate Michael reactions of enolates, silyl glyoxylates, and
      alpha,beta-enones.
AB  - Silyl glyoxylates react with enolates and enones to afford either glycolate aldol
      or Michael adducts. Product identity is controlled by the countercation
      associated with the enolate. Reformatsky nucleophiles in the presence of
      additional Zn(OTf)(2) result in aldol coupling (A), while lithium enolates
      provide the Michael coupling (B). Deprotonation of the aldol product A with LDA
      induces equilibration to form the minor diastereomer of Michael product B. This
      observation suggests that formation of the major diastereomer of Michael product
      B does not occur via an aldol/retro-aldol/Michael sequence.

PMID- 22394390
TI  - The presence and localization of onychodermis (specialized nail mesenchyme)
      containing onychofibroblasts in the nail unit: a morphological and
      immunohistochemical study.
AB  - AIMS: Due to its limited availability there has been very little research on the
      mesenchyme of the nail unit. Recently, we discovered specialized mesenchymal
      cells beneath the nail matrix and proposed to call them onychofibroblasts. The
      purpose of this study was to further delineate more precisely by histology and
      immunohistochemistry the specialized nail mesenchyme. METHODS AND RESULTS: Thirty
      supernumerary digits were obtained during operations to correct polydactyly.
      Longitudinal and transverse sections were obtained from formalin-fixed paraffin
      embedded blocks. In sections stained with haematoxylin and eosin, a mesenchymal
      area that showed much more cellularity and less eosinophilic, loose connective
      tissue was identified beneath the nail matrix and nail bed. Using Alcian blue
      staining, mucin was detected in this mesenchymal area below the nail matrix and
      nail bed. Immnunohistochemically, CD10 and versican were expressed strongly in
      the mesenchyme containing onychofibroblasts under the nail matrix and nail bed.
      CONCLUSIONS: These results demonstrate the presence and localization of a
      specialized nail mesenchyme containing onychofibroblasts in a well-defined area
      beneath the nail matrix and nail bed. Thus, we propose the term onychodermis for
      this specialized nail mesenchyme that is histologically and immunohistochemically
      distinct from the dermis of other parts of the nail unit.

PMID- 22394391
TI  - Theoretical characterization of absorption and emission spectra of an asymmetric
      porphycene.
AB  - The electronic ground and excited states of an asymmetric porphycene, 9-amino
      2,7,12,17-tetraphenylporphycene (9-ATPPo), are investigated by electronic
      structure calculations. Different tautomers are considered to address their
      contributions to the photophysics of 9-ATPPo. Tautomerization pathways on the
      ground and excited states are constructed between different isomers. It is found
      that two trans tautomers are mainly responsible for the absorption and emission
      spectra of 9-ATPPo. These calculations provide a molecular mechanism to explain
      recent experimental observations, which show a highly complex Q-band structure in
      the absorption spectrum and pronounced dual fluorescence in the emission
      spectrum. Furthermore, the current work shows that tautomerization takes place
      under the assistance of cavity deformations and that a nonradiative process
      occurs through weak interstate nonadiabatic couplings near the S(1) minimum
      rather than strong ones near conical intersections.

PMID- 22394392
TI  - Adrenergic stimulation-released 5-HT stored in adrenergic nerves inhibits
      CGRPergic nerve-mediated vasodilatation in rat mesenteric resistance arteries.
AB  - BACKGROUND AND PURPOSE: 5-HT is taken up by and stored in adrenergic nerves and
      periarterial nerve stimulation (PNS) releases 5-HT to cause vasoconstriction in
      rat mesenteric arteries. The present study investigated whether PNS-released 5-HT
      stored in adrenergic nerves affects the function of perivascular calcitonin gene
      related peptide-containing (CGRPergic) nerves. EXPERIMENTAL APPROACH: Rat
      mesenteric vascular beds without endothelium and with active tone were perfused
      with Krebs solution. Changes in perfusion pressure in response to PNS and CGRP
      injection were measured before (control) and after perfusion of Krebs solution
      containing 5-HT (10 uM) for 20 min. Distributions of 5-HT- and TH-immunopositive
      fibres in mesenteric arteries were studied using immunohistochemical methods. KEY
      RESULTS: PNS (1-4 Hz) frequency dependently caused adrenergic nerve-mediated
      vasoconstriction followed by CGRPergic nerve-mediated vasodilatation. 5-HT
      treatment inhibited PNS-induced vasodilatation without affecting exogenous CGRP
      induced vasodilatation, while it augmented PNS-induced vasoconstriction.
      Guanethidine (adrenergic neuron blocker), methysergide (non-selective 5-HT
      receptor antagonist) and BRL15572 (selective 5-HT1D receptor antagonist)
      abolished inhibition of PNS-induced vasodilatation in 5-HT-treated preparations.
      Combined treatment with 5-HT and desipramine (catecholamine transporter
      inhibitor), but not fluoxetine (selective 5-HT reuptake inhibitor), did not
      inhibit PNS-induced vasodilatation. Exogenous 5-HT inhibited PNS-induced
      vasodilatation, which was antagonized by methysergide. In immunohistochemical
      experiments, 5-HT-immunopositive nerves, colocalized with adrenergic TH
      immunopositive nerves, were observed only in 5-HT-treated mesenteric arteries,
      but not in control preparations or arteries co-treated with desipramine.
      CONCLUSIONS AND IMPLICATIONS: These results suggest that 5-HT can be taken up by
      and released from adrenergic nerves in vitro by PNS to inhibit CGRPergic nerve
      transmission in rat mesenteric arteries.

PMID- 22394394
TI  - Stem cell mediated cardiovascular repair.
AB  - Recent increase in the interest in stem and progenitor cells may be attributed to
      their behavioural characteristics. A consensus has been reached that embryonic or
      adult stem cells have therapeutic potential. As cardiovascular health issues are
      still the major culprits in many developed countries, stem and progenitor cell
      driven approaches may give the clinicians a new arsenal to tackle many
      significant health issues. However, stem and progenitor cell mediated
      cardiovascular regeneration can be achieved via complex and dynamic molecular
      mechanisms involving a variety of cells, growth factors, cytokines, and genes.
      Functional contributions of transplanted cells on target organs and their
      survival are still critical problems waiting to be resolved. Moreover, the
      regeneration of contracting myocardial tissue has controversial results in human
      trials. Thus, moderately favourable clinical results should be interpreted
      carefully. Determining the behavioural programs, genetic and transcriptional
      control of stem cells, mechanisms that determine cell fate, and functional
      characteristics are the primary targets. In addition, ensuring the long-term
      follow-up of cells with efficient imaging techniques in human clinical studies
      may provide a resurgence of the initial enthusiasm, which has faded over time.
      Here, we provide a brief historical perspective on stem cell driven cardiac
      regeneration and discuss cardiac and vascular repair in the context of
      translational science.

PMID- 22394393
TI  - Gall formation in clubroot-infected Arabidopsis results from an increase in
      existing meristematic activities of the host but is not essential for the
      completion of the pathogen life cycle.
AB  - Plasmodiophora brassicae (clubroot) infection leads to reprogramming of host
      development resulting in the formation of characteristic galls. In this work we
      explored the cellular events that underly gall formation in Arabidopsis thaliana
      with the help of molecular markers of cell division (CYCB1:GUS) and meristematic
      activity (ANT:GUS). Our results show that gall development involved the
      amplification of existing meristematic activities within the vascular cambium
      (VC) and phloem parenchyma (PP) cells in the region of the hypocotyl.
      Additionally we found that the increase in VC activity and prolonged maintenance
      of cambial-derived cells in a meristematic state was crucial for gall formation;
      disruption of the VC activity significantly decreased the gall size. Gall
      formation also perturbed vascular development with a significant reduction in
      xylem and increase in PP in infected plants. This situation was reflected in a
      decrease in transcripts of key factors promoting xylogenesis (VND6, VND7 and
      MYB46) and an increase in those promoting phloem formation and function (APL,
      SUC2). Finally we show, using the cell cycle inhibitor ICK1/KRP1 and a cle41
      mutant with altered regulation of cambial stem cell maintenance and
      differentiation, that a decrease in gall formation did not prevent pathogen
      development. This finding demonstrates that although gall formation is a typical
      symptom of the disease and influences numbers of spores produced, it is not
      required for completion of the pathogen life cycle. Together, these results
      provide an insight into the relationship of the cellular events that accompany
      Plasmodiophora infection and their role in disease progression.

PMID- 22394395
TI  - Case series of cat-scratch-inflicted full-thickness corneal lacerations and a
      review of the literature.
AB  - BACKGROUND:   To describe the clinical features and management of cat-scratch
      inflicted corneal lacerations. DESIGN:   Retrospective, observational case
      series. PARTICIPANTS:   Three patients (aged 3, 7 and 35 years) with cat-scratch
      inflicted full-thickness corneal lacerations. METHODS:   Retrospective medical
      chart review and review of the published literature. MAIN OUTCOME MEASURES:  
      Details of clinical presentation, surgical management, antibiotic treatment and
      clinical outcomes on longitudinal follow-up. RESULTS:   Cat-scratch-inflicted
      corneal lacerations are rare. Only five other cases were found in the literature.
      Wide spectrum of clinical presentation and severity of injuries exists. Two of
      the cases here required emergency surgical repair of the laceration; however, one
      case had spontaneously healed and was only diagnosed 5 years after the initial
      injury. One case required secondary cataract extraction and subsequent excision
      of a vascularized posterior lens capsule. There were no cases of secondary
      microbial keratitis or endophthalmitis. All cases had a favourable ocular outcome
      after at least 6 months of follow-up. CONCLUSIONS:   Cat-scratch-inflicted
      corneal injuries are rare but do occur in Australia, in particular among younger
      children. If the principles of prompt surgical repair and antibiotic prophylaxis
      are adhered to, excellent visual outcomes are possible.

PMID- 22394396
TI  - Schiff base protonation changes in Siberian hamster ultraviolet cone pigment
      photointermediates.
AB  - Molecular structure and function studies of vertebrate ultraviolet (UV) cone
      visual pigments are needed to understand the molecular evolution of these
      photoreceptors, which uniquely contain unprotonated Schiff base linkages between
      the 11-cis-retinal chromophore and the opsin proteins. In this study, the
      Siberian hamster ultraviolet cone pigment (SHUV) was expressed and purified in an
      n-dodecyl-beta-D-maltoside suspension for optical characterization. Time-resolved
      absorbance measurements, over a spectral range from 300 to 700 nm, were taken for
      the purified pigment at time delays from 30 ns to 4.64 s after photoexcitation
      using 7 ns pulses of 355 nm light. The resulting data were fit globally to a sum
      of exponential functions after noise reduction using singular-value
      decomposition. Four exponentials best fit the data with lifetimes of 1.4 MUs, 210
      MUs, 47 ms, and 1 s. The first photointermediate species characterized here is an
      equilibrated mixture similar to the one formed after rhodopsin's Batho
      intermediate decays into equilibrium with its successor, BSI. The extremely large
      red shift of the SHUV Batho component relative to the pigment suggests that SHUV
      Batho has a protonated Schiff base and that the SHUV cone pigment itself has an
      unprotonated Schiff base. In contrast to SHUV Batho, the portion of the
      equilibrated mixture's spectrum corresponding to SHUV BSI is well fit by a model
      spectrum with an unprotonated Schiff base. The spectra of the next two
      photointermediate species revealed that they both have unprotonated Schiff bases
      and suggest they are analogous to rhodopsin's Lumi I and Lumi II species. After
      decay of SHUV Lumi II, the correspondence with rhodopsin photointermediates
      breaks down and the next photointermediate, presumably including the G protein
      activating species, is a mixture of protonated and unprotonated Schiff base
      photointermediate species.

PMID- 22394397
TI  - Abibalsamins A and B, two new tetraterpenoids from Abies balsamea oleoresin.
AB  - Abibalsamins A (1) and B (2), two unprecedented tetraterpenoids featuring a 3,4
      seco-rearranged lanostane system fused with a beta-myrcene lateral chain via a [4
      + 2] Diels-Alder cycloaddition, were isolated from the oleoresin of Abies
      balsamea. Their structures were elucidated by means of extensive 2D NMR, IR, and
      MS spectroscopy analyses. The absolute configuration of 1 was determined by
      single-crystal X-ray diffraction. Both compounds exhibited significant cytotoxic
      activity against cancer cell lines.

PMID- 22394398
TI  - Nutritional, lifestyle and environmental factors in ocular hypertension and
      primary open-angle glaucoma: an exploratory case-control study.
AB  - PURPOSE: To evaluate known and potential risk factors, including nutritional,
      lifestyle and environmental factors, differentiating patients with high-tension
      primary open-angle glaucoma (POAG) from control subjects with ocular hypertension
      (OHT). METHODS: In 2006-2007, 111 French ophthalmologists prospectively enrolled
      339 cases of POAG and 339 age-matched controls with OHT. After a clinical
      examination with assessment of ocular risk factors, the ophthalmologist filled,
      during face-to-face interview, a detailed questionnaire developed by
      nutritionists and epidemiologist on lifestyle and environmental risk factors,
      including socio-demographic variables, dietary habits related to omega-3 fatty
      acids intake, smoking and alcohol drinking and professional exposure to
      pesticides and other chemicals. Associations of POAG with risk factors were
      estimated using conditional logistic regression, with adjustment for age, gender
      and duration of disease. RESULTS: In the final multivariate model, by comparison
      with OHT, POAG was significantly associated with more frequent use of pesticides
      during the professional life [OR = 2.65, 95% confidence interval (CI): 1.04-6.78,
      p = 0.04] and with low consumption of fatty fish (OR = 2.14, 95% CI: 1.10-4.17, p
      = 0.02) and walnuts (OR = 2.02, 95% CI: 1.18-3.47, p = 0.01). POAG was also
      associated with higher frequency of heavy smoking (40 pack-years or more, OR =
      3.93, 95% CI: 1.12-13.80, p = 0.03) but not with moderate (20-40 pack-years) and
      light smoking (<20 pack-years). CONCLUSIONS: These exploratory observations
      suggest a protective effect of omega-3 fatty acids and a deleterious effect of
      heavy smoking and professional exposure to pesticides in POAG. This will need to
      be confirmed in future studies.

PMID- 22394399
TI  - The six-minute walk test in scleroderma: what should we measure and how should we
      measure it?

PMID- 22394400
TI  - Characterization of volatiles and aroma-active compounds in honeybush (Cyclopia
      subternata) by GC-MS and GC-O analysis.
AB  - Volatile organic compounds (VOCs) in fermented honeybush, Cyclopia subternata,
      were sampled by means of a high-capacity headspace sample enrichment probe (SEP)
      and analyzed by gas chromatography-mass spectrometry (GC-MS). Stereochemistry was
      determined by means of enantioselective GC-MS with derivatized beta-cyclodextrin
      columns as chiral selectors. A total of 183 compounds, the majority of which are
      terpenoids (103; 56%), were identified by comparing their mass spectra and
      retention indices with those of reference compounds or tentatively identified by
      comparison with spectral library or literature data. Of these compounds, 37 were
      determined by gas chromatography-olfactometry (GC-O), using detection frequency
      (DF) and aroma extract dilution analysis (AEDA), to be odor-active (FD >= 2). (E)
      beta-Damascenone, (R/S)-linalool, (E)-beta-damascone, geraniol, (E)-beta-ionone,
      and (7E)-megastigma-5,7,9-trien-4-one were identified with the highest FD factors
      (>=512). The odors of certain compounds, that is, (6E,8Z)-megastigma-4,6,8-trien
      3-one, (6E,8E)-megastigma-4,6,8-trien-3-one, (7E)-megastigma-5,7,9-trien-4-one,
      10-epi-gamma-eudesmol, epi-alpha-muurolol, and epi-alpha-cadinol, were perceived
      by GC-O assessors as typically honeybush-like.

PMID- 22394401
TI  - Canopy-forming kelps as California's coastal dosimeter: 131I from damaged
      Japanese reactor measured in Macrocystis pyrifera.
AB  - The Fukushima Daiichi Nuclear Plant, damaged by an earthquake and tsunami on
      March 11, 2011 released large amounts of (131)I into the atmosphere, which was
      assimilated into canopy blades of Macrocystis pyrifera sampled from coastal
      California. The specific activity calculated to the estimated date of
      deposition/assimilation ranged from 0.6 to 2.5 Bq gdwt(-1), levels greater than
      those measured from kelps from Japan and Canada prior to the release. These
      (131)I levels represent a significant input into the kelp forest ecosystem.
      Canopy-forming kelps are a natural coastal dosimeter that can measure the
      exposure of the coastal environment to (131)I and perhaps other radioisotopes
      released from nuclear accidents. An organizational mechanism should be in place
      to ensure that they are sampled immediately and continuously after such releases.

PMID- 22394402
TI  - Neural and behavioral correlates of peritraumatic dissociation in an acutely
      traumatized sample.
AB  - OBJECTIVE: Peritraumatic dissociative responses have been identified as strong
      predictors of subsequent posttraumatic stress disorder development. We aimed to
      clarify the mechanism by which peritraumatic dissociation is related to PTSD
      development by exploring the neural correlates of peritraumatic dissociation
      during posttraumatic adjustment. METHOD: We combined a prospective questionnaire
      study with a neuroimaging paradigm in an acutely traumatized sample recruited
      from the emergency department from 2004 until 2009. 121 acutely traumatized
      subjects were assessed for acute stress disorder, PTSD, and dissociative symptoms
      at 3 time points within the first 3 months post trauma. A subsample of 21
      subjects underwent a script-driven 4-Tesla functional magnetic resonance imaging
      scan 2 to 4 months post trauma. RESULTS: Peritraumatic dissociation predicted
      PTSD diagnostic status at 5-6 weeks and 3 months over and above childhood trauma
      (Wald = 4.035, P = .045; Wald = 4.793, P = .029, respectively). Peritraumatic
      dissociation scores were positively correlated with activation in the right
      occipital lobe, ie, the lingual (Brodmann area [BA] 18, z = 3.37), fusiform (BA
      19, z = 3.64), and parahippocampal (BA 19, z = 3.25) gyri. After covariation of
      dissociation at the time of the scan, peritraumatic dissociation remained
      positively correlated with activation in the right lingual (BA 18, z = 3.21) and
      fusiform (BA 19, z = 3.55) gyri. CONCLUSIONS: The neuroimaging findings indicate
      that peritraumatic dissociation is associated with greater activation of the
      right occipital lobe (BAs 18 and 19), a region previously implicated in vivid
      autobiographical memory recall of highly emotional events. These results suggest
      that peritraumatic dissociation directly leads to the formation of intrusive
      memories. Peritraumatic dissociation and childhood trauma emerged as valuable
      predictors of PTSD development and therefore can guide the identification of
      individuals at risk.

PMID- 22394403
TI  - Formation of optically pure cyclic amines by intramolecular conjugate
      displacement.
AB  - Intramolecular conjugate displacement (ICD) has been applied to the Morita-Baylis
      Hillman adducts formed from (5S)-5-(l-menthyloxy)-2(5H)-furanone and aldehydes
      that carry a protected beta- or gamma-amino group. DIBAL-H reduction of the
      resulting ICD products releases optically pure six- or seven-membered cyclic
      amines having a stereogenic center alpha to nitrogen.

PMID- 22394404
TI  - Covalent binding of cisplatin impairs the function of Na(+)/K(+)-ATPase by
      binding to its cytoplasmic part.
AB  - This study was aimed at verifying the hypothesis that acute kidney failure
      accompanying cisplatin administration in the cancer therapy could be due to
      cisplatin interaction with the cytoplasmic part of Na(+)/K(+)-ATPase. Our results
      demonstrated that cisplatin-binding caused inhibition of Na(+)/K(+)-ATPase, in
      contrast to other platinated chemotherapeutics such as carboplatin and
      oxaliplatin, which are known to be much less nephrotoxic. To acquire more
      detailed structural information, we performed a series of experiments with the
      isolated large cytoplasmic segment connecting transmembrane helices 4 and 5 (C45
      loop) of Na(+)/K(+)-ATPase. Electrochemistry showed that cisplatin is bound to
      the cysteine residues of the C45 loop, mass spectrometry revealed a modification
      of the C45 peptide fragment GSHMASLEAVETLGSTSTICSDK, which contains the conserved
      phosphorylated residue Asp369. Hence, we hypothesize that binding of cisplatin to
      Cys367 can cause sterical obstruction during the phosphorylation or
      dephosphorylation step of the Na(+)/K(+)-ATPase catalytic cycle.

PMID- 22394405
TI  - An investigation into the reporting and management of late terminations of
      pregnancy (between 22 +0 and 26 +6 weeks of gestation) within NHS Hospitals in
      England in 2006: the EPICure preterm cohort study.
AB  - OBJECTIVE: To review all late terminations of pregnancy, between 22(+0) and
      26(+6) weeks of gestation, collected as part of the EPICure2 study. DESIGN:
      Prospective cohort study. SETTING: All National Health Service (NHS) hospitals
      providing perinatal services for extremely preterm infants. POPULATION: All
      births between 22(+0) and 26(+6) weeks of gestation in England during 2006.
      METHODS: Data were collected for the defined cohort of births, including
      terminations of pregnancy, by designated unit staff using a standardised
      questionnaire. Rigorous validation processes were established to ensure
      comprehensive data collection. Gestational age was validated using a hierarchical
      classification of scan dates, certain date of last menstrual period and working
      gestation. Data for terminations of pregnancy (TOPs) were categorised into two
      groups, terminations for fetal abnormality and for maternal or fetal compromise,
      and were analysed in terms of their reporting, management and outcomes. MAIN
      OUTCOME MEASURES: Classification, rate of feticide and outcome following TOP.
      RESULTS: Of 3782 births between 22(+0) and 26(+6) weeks of gestation, 647 (17.1%)
      were TOPs; of these 584 (90.3%) were for fetal abnormality and 63 (9.7%) for
      maternal or fetal compromise. Feticide was carried out in 489 of 584 (83.7%) TOPs
      for fetal abnormality, and in 38 of 63 (60.3%) of the TOPs for maternal or fetal
      compromise. Live births resulted following 2.2% TOPs for fetal abnormality and
      4.8% TOPs for maternal or fetal compromise. CONCLUSION: Terminations of pregnancy
      represent a relatively large proportion of very preterm births. Fetal
      abnormalities are the main cause for these terminations, and most include
      feticide. Better screening strategies are required to avoid the need for late
      terminations of pregnancy for fetal abnormalities.

PMID- 22394406
TI  - The elevated T-maze task as an animal model to simultaneously investigate the
      effects of drugs on long-term memory and anxiety in mice.
AB  - The elevated T-maze (ETM) is an apparatus derived from the elevated plus-maze
      test, which is used to evaluate anxiety. Because anxiety is a biasing factor in
      models of memory, this study proposed the ETM as a task for the simultaneous
      assessment of memory and anxiety in mice. The ETM consists of one enclosed and
      two open arms. The procedure is based on the avoidance of open spaces learned
      during training session, in which mice were exposed to the enclosed arm as many
      times as needed to stay 300s. In the test session, memory is assessed by re
      exposing the mouse to the enclosed arm and the latency to enter an open arm was
      recorded. The anxiolytic diazepam (DZP; 1 or 2mg/kg) and the amnestic biperiden
      (BPR; 0.5, 1 or 3mg/kg) were injected at three distinct times: pre-training, post
      training, and pre-test. Pre-training administration of BPR 1 and DZP 2 increased
      the number of trials needed to reach the avoidance criterion, suggesting a
      passive avoidance learning impairment. However, BPR induced hyperlocomotion,
      which could bias the interpretation of any BPR-induced effects during the
      training session. Pre-training injection of BPR did not affect the spontaneous
      increase in the latency to enter an open arm between trials, while DZP reduced
      latencies in the first three trials suggesting anxiolysis. In the test session,
      pre-training injection of BPR 1 and DZP 2 reduced latencies to enter an open arm,
      indicating memory impairment. Post-training and pre-test injection of DZP or BPR
      did not affect memory. In conclusion, the proposed ETM task is practical for the
      detection of the anxiolytic and amnesic effects of drugs.

PMID- 22394407
TI  - Reelin regulates differentiation of neural stem cells by activation of notch
      signaling through Disabled-1 tyrosine phosphorylation.
AB  - We have previously reported the cross-talk between Reelin and Notch-1 signaling
      pathways, which are 2 major pathways that regulate brain development. We found
      that Reelin activated Notch-1 signaling, leading to the expression of brain lipid
      binding protein (BLBP) and the formation of radial glial cells in human neural
      progenitor cells (hNPCs). In the current study, we investigated the molecular
      mechanisms by which Reelin activates Notch-1. We show that Reelin-stimulated
      Notch-1 activation is dependent on Reelin signaling. The induction of Disabled-1
      (Dab-1) tyrosine phosphorylation, and the subsequent activation of Src family
      kinases, were found to be essential steps for the activation of Notch-1 signaling
      by Reelin. Reelin treatment increased the interaction between Dab-1 and Notch-1
      intracellular domain (NICD), and enhanced NICD translocation to the nucleus. This
      study advances our knowledge of the regulation of Notch-1 activation by Reelin
      signaling in hNPCs, as an approach to understanding cell fate determination,
      differentiation, and neurogenesis during brain development.

PMID- 22394408
TI  - Vignettes of a life in hydrogeology.

PMID- 22394409
TI  - Pv12, a 6-Cys antigen of Plasmodium vivax, is localized to the merozoite rhoptry.
AB  - Pf12 in Plasmodium falciparum has been characterized as a merozoite surface
      protein and the Pf12 gene is actively transcribed during schizont stage. An
      orthologous gene, Pv12, has been identified in genome of P. vivax, but the
      protein product has not been characterized. The Pv12 is a 362 amino acid long
      polypeptide encoded by a single exon gene PVX_113775, for which orthologous genes
      have been identified in other Plasmodium species by bioinformatic approaches.
      Pv12 contains two predicted six-cysteine (6-Cys) domains, which may be
      constrained by predicted disulfide bonds, and a transmembrane domain and a
      predicted GPI anchor attachment site in C-terminal region. The recombinant Pv12
      protein is recognized by serum antibodies of patients naturally exposed to P.
      vivax and the native Pv12 protein from parasite extract is also recognized by
      immune mouse serum. The Pv12 is localized in rhoptry; an apical organelle of the
      merozoite, and the localization pattern of Pv12 is distinct from that of Pf12 in
      P. falciparum. The present study suggests that Pv12 is immunogenic in humans
      during parasite infection and it could play an important role in erythrocyte
      invasion.

PMID- 22394410
TI  - Pulmonary sclerosing haemangioma with metastatic spread to stomach.

PMID- 22394411
TI  - Damping of intraocular pressure fluctuations.
AB  - BACKGROUND: There is increasing evidence that relatively rapid spikes in
      intraocular pressure may contribute to axonal damage in glaucoma. The present
      study seeks to quantify the ability of a compressible damping element (a simple
      air bubble) to reduce intraocular pressure fluctuations induced by a known change
      in intraocular fluid volume. METHODS: A mathematical model describing the damping
      of intraocular pressure increases for a given infusion volume was developed and
      compared with experimental data obtained from isolated pig eyes. A damping
      element (100 uL to 2 mL of air) was added to the system, and the effect on the
      induced intraocular pressure change for a given infusion volume was assessed.
      RESULTS: The introduction of the damping element reduced the intraocular pressure
      change in a volume-dependent manner consistent with the mathematical modelling.
      The maximum bubble size tested (2 mL) dampened the intraocular pressure change by
      an average of 63.5 +/- 8.7% at a baseline pressure close to 20 mmHg. Close
      agreement was seen between the mathematical model and the experimental data.
      CONCLUSION: Mathematical modelling and experiments in isolated pig eyes
      demonstrated that the addition of a damping element in the form of a compressible
      air bubble is capable of significantly reducing induced intraocular pressure
      spikes.

PMID- 22394412
TI  - Intravenous diuretic and vasodilator therapy reduce plasma brain natriuretic
      peptide levels in acute exacerbation of chronic obstructive pulmonary disease.
AB  - BACKGROUND AND OBJECTIVE: Plasma concentrations of brain natriuretic peptide
      (BNP) are elevated in patients with chronic obstructive pulmonary disease (COPD),
      and high plasma BNP levels are associated with a poor prognosis. We aimed to
      evaluate the effects of a diuretic and a vasodilator on plasma BNP levels and
      health-related quality of life (HRQOL) in patients with acute exacerbations of
      COPD (AECOPD). METHODS: Forty patients with an AECOPD and high plasma BNP levels,
      but without any clinical evidence of cor pulmonale, were selected. The patients
      were randomly divided into two groups of 20 patients. In addition to standard
      treatment for AECOPD, the patients in group I were treated with a mild diuretic,
      and those in group II were treated with the diuretic and a vasodilator. Twenty
      patients with stable COPD were selected as a control group. Plasma BNP
      concentrations were measured on admission and on the third and sixth days. The
      patients' HRQOL was evaluated using the short-form 36-item (SF-36) questionnaire
      before and after treatment. RESULTS: Plasma BNP concentrations in patients with
      AECOPD were significantly decreased after treatment, and this decrease was more
      striking in group II than in group I. There were no significant differences in SF
      36 domain scores between patients with stable COPD and those with acute
      exacerbations who were treated with a diuretic and a vasodilator. CONCLUSIONS:
      Plasma BNP levels decreased rapidly in patients with an AECOPD after therapy with
      a diuretic and a vasodilator, and the treatment did not impair their health
      status.

PMID- 22394413
TI  - High-resolution characterization of organic phosphorus in soil extracts using 2D
      1H-31P NMR correlation spectroscopy.
AB  - Organic phosphorus (P) compounds represent a major component of soil P in many
      soils and are key sources of P for microbes and plants. Solution NMR (nuclear
      magnetic resonance spectroscopy) is a powerful technique for characterizing
      organic P species. However, (31)P NMR spectra are often complicated by
      overlapping peaks, which hampers identification and quantification of the
      numerous P species present in soils. Overlap is often exacerbated by the presence
      of paramagnetic metal ions, even if they are in complexes with EDTA following
      NaOH/EDTA extraction. By removing paramagnetic impurities using a new
      precipitation protocol, we achieved a dramatic improvement in spectral
      resolution. Furthermore, the obtained reduction in line widths enabled the use of
      multidimensional NMR methods to resolve overlapping (31)P signals. Using the new
      protocol on samples from two boreal humus soils with different Fe contents, 2D
      (1)H-(31)P correlation spectra allowed unambiguous identification of a large
      number of P species based on their (31)P and (1)H chemical shifts and their
      characteristic coupling patterns, which would not have been possible using
      previous protocols. This approach can be used to identify organic P species in
      samples from both terrestrial and aquatic environments increasing our
      understanding of organic P biogeochemistry.

PMID- 22394414
TI  - Foldable iris-fixated intraocular lens implantation in children.
AB  - PURPOSE:   To describe the results of foldable iris-fixated intraocular lens
      (IOL) implantation in children. METHODS:   Children with high bilateral or
      unilateral myopia who were intolerant of spectacle or contact lens correction
      were implanted with an iris-fixated foldable IOL and prospectively followed. We
      measured pre- and postoperative visual acuity, refraction, endothelial cell
      density (ECD) and National Eye Institute Visual Functioning Questionnaire-25.
      RESULTS:   Eleven eyes of six children were implanted. Indications were high
      bilateral myopia in children with comorbid neurobehavioural disorders, high
      anisometropia and high myopic astigmatism. Mean preoperative spherical equivalent
      (SE) refraction was -14.6 dioptres (D)+/-4.2 SD. Mean follow-up was 15 months.
      Postoperative SE refraction was -2.40 D+/-2.40 SD. Corrected distance visual
      acuity (CDVA) improved from mean logMAR 0.84+/-0.4 SD to postoperative 0.67+/
      0.34 SD (p=0.005). CDVA was reduced because of coexistent ocular disorders and
      amblyopia. Vision-related quality of life (QOL) measures improved significantly.
      There were no intraoperative or postoperative serious complications. CONCLUSION: 
      Foldable iris-fixated IOL insertion can give a significant improvement in vision
      and in vision-related QOL in a subset of paediatric patients with special
      refractive needs who are intolerant to conventional treatment. Long-term follow
      up is required for monitoring of ECD.

PMID- 22394416
TI  - Brain-volume increase with sustained remission in patients with treatment
      resistant unipolar depression.
AB  - OBJECTIVE: Previous magnetic resonance imaging (MRI) studies have demonstrated
      brain-volume reductions in unipolar major depressive disorder (MDD). It is not
      clear whether these atrophic changes can be stabilized with antidepressant
      treatment and/or reversed with remission. The objective of this study was to
      prospectively examine brain-volume changes in patients with treatment-resistant
      depression, comparing those who achieved sustained remission with those who did
      not remit. METHOD: This prospective observational cohort study investigated the
      roles of clinical responsiveness and antidepressant treatment in lessening brain
      atrophy in depression. Data were collected between October 2004 and December
      2008. Baseline MRI scans were obtained from 28 outpatients with treatment
      resistant MDD (diagnosed according to DSM-IV criteria) who were recruited from
      the Mood Disorders Research Unit at the Royal Ottawa Mental Health Centre,
      Ottawa, Ontario, Canada. Twenty-seven patients underwent follow-up scanning after
      either 6 months of sustained remission (Montgomery-Asberg Depression Rating Scale
      score <= 12) or 12 months of failure to remit. Longitudinal whole-brain and voxel
      based gray- and white-matter volume changes were estimated. RESULTS: Twelve
      patients (mean age at baseline = 47.5 years) achieved sustained 6-month
      remission. In contrast to nonremitters (n = 15; mean age at baseline = 44.3
      years), remitted patients demonstrated a significant mean increase in whole-brain
      volume during follow-up (F(1,27) = 9.51, P = .005). Within-subject voxel-based
      morphometry analyses identified increased gray-matter volume in remitters in the
      right orbitofrontal cortex (t(11) = 7.61, P = .006) and the right inferior
      temporal gyrus (t(11) = 6.65, P = .004). Nonremitters showed decreased white
      matter volume in the left anterior limb of the internal capsule (t(13) = 3.86, P
      = .04). CONCLUSIONS: Given that remitters exhibited a mean increase in brain
      volume while nonremitters lost volume, pharmacotherapy in the absence of
      sustained remission is most likely insufficient to elicit brain-volume increase
      in MDD. The findings suggest that clinical remission rather than pharmacotherapy
      may be the key factor involved in driving volumetric recovery in treatment
      resistant depression.

PMID- 22394415
TI  - Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway
      in intracerebral hemorrhage.
AB  - BACKGROUND: Inflammatory injury plays a critical role in intracerebral hemorrhage
      (ICH)-induced neurological deficits; however, the signaling pathways are not
      apparent by which the upstream cellular events trigger innate immune and
      inflammatory responses that contribute to neurological impairments. Toll-like
      receptor 4 (TLR4) plays a role in inflammatory damage caused by brain disorders.
      METHODS: In this study, we investigate the role of TLR4 signaling in ICH-induced
      inflammation. In the ICH model, a significant upregulation of TLR4 expression in
      reactive microglia has been demonstrated using real-time RT-PCR. Activation of
      microglia was detected by immunohistochemistry, cytokines were measured by ELISA,
      MyD88, TRIF and NF-kappaB were measured by Western blot and EMSA, animal behavior
      was evaluated by animal behavioristics. RESULTS: Compared to WT mice, TLR4(-/-)
      mice had restrained ICH-induced brain damage showing in reduced cerebral edema
      and lower neurological deficit scores. Quantification of cytokines including IL
      6, TNF-alpha and IL-1beta and assessment of macrophage infiltration in
      perihematoma tissues from TLR4(-/-), MyD88(-/-) and TRIF(-/-) mice showed
      attenuated inflammatory damage after ICH. TLR4(-/-) mice also exhibited reduced
      MyD88 and TRIF expression which was accompanied by decreased NF-kappaB activity.
      This suggests that after ICH both MyD88 and TRIF pathways might be involved in
      TLR4-mediated inflammatory injury possibly via NF-kappaB activation. Exogenous
      hemin administration significantly increased TLR4 expression and microglial
      activation in cultures and also exacerbated brain injury in WT mice but not in
      TLR4(-/-) mice. Anti-TLR4 antibody administration suppressed hemin-induced
      microglial activation in cultures and in the mice model of ICH. CONCLUSIONS: Our
      findings suggest that heme potentiates microglial activation via TLR4, in turn
      inducing NF-kappaB activation via the MyD88/TRIF signaling pathway, and
      ultimately increasing cytokine expression and inflammatory injury in ICH.
      Targeting TLR4 signaling may be a promising therapeutic strategy for ICH.

PMID- 22394417
TI  - The growth in newspaper coverage of tobacco control in China, 2000-2010.
AB  - BACKGROUND: Media coverage of tobacco-related issues can potentially shape
      individual beliefs, attitudes and behaviors about tobacco use. This study aims to
      describe news coverage of tobacco control related issues in Chinese newspapers
      from 2000 to 2010. METHODS: All 1149 articles related to tobacco control were
      extracted from the Database of Chinese Important Newspapers and content analyzed
      for the period Jan 1, 2000 to Dec 31, 2010. The changing pattern of tobacco
      control topic, article type, viewpoint, and article origin, and their
      relationship were analysed. RESULTS: News coverage of tobacco control related
      issues increased significantly (p < 0.01) from 2000 to 2010, with news coverage
      being relatively intensive in May and June (p < 0.01), around World No Tobacco
      Day. 24.9% (n = 286) of all articles focused on secondhand smoke, 25.3% (n = 291)
      warned about the dangers of active smoking, and 10.0% (n = 115) focused on
      prevention and cessation programs and campaigns. Tobacco control topics varied
      significantly between national vs city/regional newspapers (chi2 = 24.09, p =
      0.002) and article types (chi2 = 193.35, p < 0.001). Articles in national
      newspapers had more coverage of the dangers of tobacco and on enforcing bans on
      tobacco-advertising. News stories centered around monitoring tobacco use and
      smoke free activity, while editorials focused on enforcing bans on tobacco
      advertising, youth access and programs and campaigns. Letters to editors focused
      on the dangers of smoking, raising tax, and smoking cessation. More articles
      (50.4%) took an anti-tobacco position (compared with 10.5% which were pro
      smoking), with the amount of negative coverage growing significantly across the
      decade. National articles tended to lean toward anti-tobacco, however, local
      articles tended mix of pro-tobacco and neutral/balance positions. Editorials
      seemed to be more anti-tobacco oriented, but letters to the editor tended to show
      a mix of anti-tobacco and pro-tobacco positions. CONCLUSION: Chinese newspapers
      are giving increasing attention to tobacco control, but coverage remains lower
      than in the USA and Australia. Health workers need to give higher priority to
      efforts to increase news coverage beyond the present concentration around World
      No Tobacco Day and to develop strategies for making tobacco control issues more
      newsworthy to both national and local news outlets.

PMID- 22394419
TI  - Penile calciphylaxis: an unusual cause of penile necrosis.

PMID- 22394418
TI  - Bifurcation angioplasty using drug eluting stents of post-AF ablation severe
      pulmonary vein stenosis.
AB  - A 53-year-old man with long-standing persistent AF underwent multiple ablation
      procedures. A presentation with hemoptysis led to a left pulmonary artery wedge
      angiography and thoracic computed tomography (CT) scan, which revealed a tight
      bifurcation stenosis of the left superior pulmonary vein (LSPV). This was treated
      by angioplasty with drug-eluting stents to avoid restenosis by bare-metal stent
      implantation in small diameter PVs as already described. After predilatation, two
      4 * 32-mm and a 3 * 20-mm Taxus(r) Liberte stents (Boston Scientific, Natick, MA,
      USA) were deployed across upper and lower LSPV branches and the ostio-antral
      segment. Twenty-two month follow-up CT angiography showed patent stents in the
      LSPV, without in-stent restenosis (no arrhythmia or hemoptysis at 24-month follow
      up).

PMID- 22394420
TI  - A twin study of computer anxiety in Turkish adolescents.
AB  - The present study investigated computer anxiety within a sample of Turkish twins
      aged 10-18. A total of 185 twin-pairs participated in the study. Of the twins, 64
      pairs (34.6 percent) were monozygotic (MZ) and 121 pairs (65.4 percent) were
      dizygotic (DZ). Of the 121 DZ twins, 54 pairs (44.63 percent) were same-sex twins
      and 67 pairs (55.37 percent) were opposite-sex twins. Computer anxiety was
      assessed using Computer Anxiety Rating Scale-Turkish Version (CARS-TV), one of
      the three main scales of "Measuring Technophobia Instruments" developed by Rosen
      and Weil. The results of paired t test comparisons showed no significant
      differences in MZ and same-sex DZ twin-pairs' levels of computer anxiety. On the
      other hand, a significant difference was found in opposite-sex DZ twin-pairs'
      level of computer anxiety. Interesting enough, males appeared to be more computer
      anxious than their female co-twins. In the present study, using Falconer's
      formula, heritability estimate for computer anxiety was derived from correlations
      based on MZ and DZ twins' mean scores on CARS-TV. The results showed that 57
      percent of the variance in computer anxiety was from genetics and 41.5 percent
      was from nonshared environmental factors. Shared environmental influence, on the
      other hand, was very small and negligible. Interpretations of results and
      potential directions for future research are presented.

PMID- 22394421
TI  - Same same but different!? The differential influence of smilies and emoticons on
      person perception.
AB  - Emoticons (ASCII-based character strings) and smilies (pictograms) are widely
      used in computer-mediated communication as substitutes to compensate for the
      absence of nonverbal cues. Although their usage has been investigated in numerous
      studies, it remains open whether they provoke differential effects and whether
      they lead to person perception patterns similar to what is known from face-to
      face interactions. Based on findings from research about person perception and
      nonverbal communication, we investigated the differential effects of smilies and
      emoticons with regard to recipients' mood, message evaluation, and person
      perception in an experimental online study (n=127) with a 2(smiley/emoticon) by
      2(positive/negative) between-subjects design (with an additional control
      condition). Results generally support earlier findings, indicating that the
      valence of the cue (smiley or emoticon) affects the corresponding impression
      formation. Further, findings concerning the differential influence of both forms
      of cues show that there are no differences with regard to message interpretation,
      whereas smiling smilies have a stronger impact on personal mood than smiling
      emoticons. The perception of a writer's commitment was only altered by smilies,
      suggesting that they elicit a stronger impact than emoticons.

PMID- 22394422
TI  - The meaning and consequences of tuberculosis among Somali people in the United
      Kingdom.
AB  - AIM: To ascertain the socio-cultural meaning and consequences of tuberculosis
      among people of Somali origin living in the UK. BACKGROUND: In countries where
      treatment has not been readily available, tuberculosis has become highly
      stigmatized. Research in Somalia has documented the stigma and social isolation
      associated with tuberculosis which acts as a powerful deterrent to sufferers
      acknowledging their illness. The Somali community in the UK is diverse and
      dynamic: little is known about how tuberculosis is understood, or how stigma is
      articulated and experienced post-migration. DESIGN: A focused ethnography was
      undertaken. METHOD: A total of 48 individual interviews were undertaken in 2008
      2009 with community leaders, Somali community members and tuberculosis patients
      to explore the social meaning of tuberculosis and perceived consequences of the
      disease. Eight focus groups were undertaken involving 56 participants. Vignettes
      concerning tuberculosis were used to prompt discussion of community norms and
      socio-cultural constructions of tuberculosis. Data were analysed using the
      'Framework' approach. FINDINGS: Most participants were familiar with
      tuberculosis, its characteristics and treatment. However, many participants held
      misconceptions about how the disease spread and its prognosis. Tuberculosis was
      perceived as a stigmatizing disease. Somalis with tuberculosis were considered
      likely to experience felt and enacted stigma with fear of discrimination in the
      form of social isolation influencing the extent to which people with tuberculosis
      disclosed their condition. CONCLUSION: Nurses should understand the socio
      cultural meaning and consequences of tuberculosis for Somalis to educate the
      community through public health initiatives and support patients and their
      families.

PMID- 22394423
TI  - Factor seven-activating protease: does it do what it says on the tin?

PMID- 22394426
TI  - Evaluation of stable isotope tracing for ZnO nanomaterials--new constraints from
      high precision isotope analyses and modeling.
AB  - This contribution evaluates two possible routes of stable isotope tracing for ZnO
      nanomaterials. For this we carried out the first high precision Zn isotope
      analyses of commercially available ZnO nanomaterials, to investigate whether such
      materials exhibit isotope fractionations that can be exploited for tracing
      purposes. These measurements revealed Zn isotopic compositions (of delta(66/64)Zn
      = +0.28 to -0.310/00 relative to JMC Lyon Zn) that are indistinguishable from
      "normal" natural and anthropogenic Zn in environmental samples. Stable isotope
      tracing therefore requires the application of purpose-made isotopically enriched
      ZnO nanoparticles. A detailed evaluation identified the most suitable and cost
      effective labeling isotopes for different analytical requirements and techniques.
      It is shown that, using relatively inexpensive (68)Zn for labeling, ZnO
      nanoparticles can be reliably detected in natural samples with a Zn background of
      100 MUg/g at concentrations as low as about 5 ng/g, if the isotopic tracing
      analyses are carried out by high precision mass spectrometry. Stable isotope
      tracing may also be able to differentiate between the uptake by organisms of
      particulate ZnO and Zn(2+) ions from the dissolution of nanoparticles.

PMID- 22394427
TI  - Quantitative study of cytotoxic T-lymphocyte immunotherapy for nasopharyngeal
      carcinoma.
AB  - BACKGROUND: In clinical practice, the common strategy for immunotherapy of
      nasopharyngeal carcinoma (NPC) is to infuse cytotoxic T-lymphocyte (CTL) lines
      several times by intravenous injection, but it is difficult by laboratory
      research to investigate the relationship between treatment time-point, the amount
      of CTL added and the therapeutic effect. The objective of this study is to
      establish a mathematical model to study the therapeutic effect of different
      treatment time-points and amounts of CTL, and to predict the change in
      therapeutic effect when the percentage of EBV LMP2-specific CTL is increased from
      10% to 20%. RESULTS: The concentration of epidermal growth factor receptor (EGFR)
      in the tumor cell cytomembranes increases after CTL is added. Concurrently, there
      is a marked downward trend of the phosphorylated transforming growth factor-alpha
      (TGFalpha)-EGFR complex in the tumor cell cytomembranes, which indicates
      restriction of tumor growth after CTL immunotherapy. The relationships among the
      time of addition of CTL, the amount of CTL added, different CTL specificities for
      LMP2 and the increment rate k of the total number of tumor cells were evaluated.
      CONCLUSIONS: The simulation results quantify the relationships among treatment
      time-points, amount of CTL added, and the corresponding therapeutic effect of
      immunotherapy for NPC.

PMID- 22394424
TI  - Annual research review: progress in using brain morphometry as a clinical tool
      for diagnosing psychiatric disorders.
AB  - Brain morphometry in recent decades has increased our understanding of the neural
      bases of psychiatric disorders by localizing anatomical disturbances to specific
      nuclei and subnuclei of the brain. At least some of these disturbances precede
      the overt expression of clinical symptoms and possibly are endophenotypes that
      could be used to diagnose an individual accurately as having a specific
      psychiatric disorder. More accurate diagnoses could significantly reduce the
      emotional and financial burden of disease by aiding clinicians in implementing
      appropriate treatments earlier and in tailoring treatment to the individual
      needs. Several methods, especially those based on machine learning, have been
      proposed that use anatomical brain measures and gold-standard diagnoses of
      participants to learn decision rules that classify a person automatically as
      having one disorder rather than another. We review the general principles and
      procedures for machine learning, particularly as applied to diagnostic
      classification, and then review the procedures that have thus far attempted to
      diagnose psychiatric illnesses automatically using anatomical measures of the
      brain. We discuss the strengths and limitations of extant procedures and note
      that the sensitivity and specificity of these procedures in their most successful
      implementations have approximated 90%. Although these methods have not yet been
      applied within clinical settings, they provide strong evidence that individual
      patients can be diagnosed accurately using the spatial pattern of disturbances
      across the brain.

PMID- 22394429
TI  - Relation of biometric eye profile with intraocular pressure corrections in
      healthy myopes.

PMID- 22394428
TI  - Risks for the transition from major depressive disorder to bipolar disorder in
      the National Epidemiologic Survey on Alcohol and Related Conditions.
AB  - OBJECTIVE: It is currently not possible to determine which individuals with
      unipolar depression are at highest risk for a manic episode. This study
      investigates clinical and psychosocial risk factors for mania among individuals
      with major depressive disorder (MDD), indicating diagnostic conversion from MDD
      to bipolar I disorder. METHOD: We fitted logistic regression models to predict
      the first onset of a manic episode among 6,214 cases of lifetime MDD according to
      DSM-IV criteria in the National Epidemiologic Survey on Alcohol and Related
      Conditions. Participants in this survey were interviewed twice over a period of 3
      years, in 2000-2001 and in 2004-2005, and survey data were gathered using the
      Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV. RESULTS:
      Approximately 1 in 25 individuals with MDD transitioned to bipolar disorder
      during the study's 3-year follow-up period. Demographic risk factors for the
      transition from MDD to bipolar disorder included younger age, black
      race/ethnicity, and less than high school education. Clinical characteristics of
      depression (eg, age at first onset, presence of atypical features) were not
      associated with diagnostic conversion. However, prior psychopathology was
      associated with the transition to bipolar disorder: history of social phobia
      (odds ratio [OR] = 2.20; 95% confidence interval [CI], 1.47-3.30) and generalized
      anxiety disorder (OR = 1.58; 95% CI, 1.06-2.35). Lastly, we identified
      environmental stressors over the life course that predicted the transition to
      bipolar disorder: these include a history of child abuse (OR = 1.26; 95% CI, 1.12
      1.42) and past-year problems with one's social support group (OR = 1.79; 95% CI,
      1.19-2.68). The overall predictive power of these risk factors based on a
      receiver operating curve analysis is modest. CONCLUSIONS: A wide range of
      demographic, clinical, and environmental risk factors were identified that
      indicate a heightened risk for the transition to bipolar disorder. Additional
      work is needed to further enhance the prediction of bipolar disorder among cases
      of MDD and to determine whether interventions targeting these factors could
      reduce the risk of bipolar disorder.

PMID- 22394432
TI  - Continuous versus intermittent monitoring of ventricular rate in patients with
      permanent atrial fibrillation.
AB  - BACKGROUND: Ventricular rate control (VRC) is an important treatment strategy for
      patients with permanent atrial fibrillation (AF). We assessed the prevalence of
      poor VRC and the adequacy of various intermittent monitoring regimens to
      accurately characterize VRC during permanent AF. METHODS: We retrospectively
      analyzed data from dual chamber implantable cardioverter defibrillator (ICD) and
      cardiac resynchronization therapy defibrillator (CRT-D) patients in the Medtronic
      DiscoveryTM Link having permanent AF (AF burden >23 hours/day) and >= 365
      consecutive days of device data. Poor VRC was defined as a day with the mean
      ventricular rate during AF >100 beats/minute (bpm) for ICD patients and >90 bpm
      for CRT-D patients. Intermittent monitoring regimens were simulated from
      continuous device data by randomly selecting subsets of days in which data were
      available for analysis. Assessments of poor VRC were computed after replicating
      1,000 simulations. RESULTS: ICD (n = 1,902, age = 71 +/- 10) and CRT-D (n =
      3,397, age = 72 +/- 9) patients were included and followed for 365 days. The
      prevalence of poor VRC was 24.8% among ICD patients and 28.6% among CRT-D
      patients. Significantly more patients were identified as having poor VRC with
      continuous monitoring compared to all intermittent monitoring regimens
      (sensitivity range = 8%-31%). Furthermore, 11.6% of ICD patients and 17.9% of CRT
      D patients experienced >= 7 days with poor VRC, to which the sensitivities of
      annual 7- and 21-day recordings were <7% and <20%, respectively. CONCLUSIONS: A
      significant proportion of permanent AF patients experience poor VRC that would be
      missed with random intermittent monitoring. Whether improved knowledge of VRC
      with continuous monitoring will lead to improved outcomes compared to
      intermittent monitoring requires further study.

PMID- 22394430
TI  - Prognostic significance of the complex "Visceral Adiposity Index" vs. simple
      anthropometric measures: Tehran lipid and glucose study.
AB  - BACKGROUND: Visceral adiposity index (VAI) has recently been suggested to be used
      as a surrogate of visceral adiposity. We examined if VAI could improve predictive
      performances for CVD of the Framingham's general CVD algorithm (a multivariate
      model incorporating established CVD risk factors). We compared the predictive
      abilities of the VAI with those of simple anthropometric measures i.e. BMI, waist
      to-height ratio (WHtR) or waist-to-hip ratio (WHpR). DESIGN AND METHODS: In a
      nine-year population-based follow-up, 6,407 (2,778 men) participants, free of CVD
      at baseline, aged>=30 years were eligible for the current analysis. The risk of
      CVD was estimated by incorporating VAI, BMI, WHpR, and WHtR, one at a time, into
      multivariate accelerated failure time models. RESULTS: We documented 534 CVD
      events with the annual incidence rate (95%CIs) being 7.3 (6.4-8.3) among women
      and 13.0 (11.7-14.6) among men. Risk of future CVD increased with increasing
      levels of VAI among both men and women. VAI was associated with multivariate
      adjusted increased risk of incident CVD among women. However, the magnitude of
      risk conferred by VAI was not significantly higher than those conferred by BMI,
      WHpR, or WHtR. Among men, after adjustment for established CVD risk factors, VAI
      was no longer associated with increased risk of CVD. VAI failed to add to the
      predictive ability of the Framingham general CVD algorithm. CONCLUSIONS: Using
      VAI instead of simple anthropometric measures may lead to loss of much
      information needed for predicting incident CVD.

PMID- 22394433
TI  - Statin use and risk of depression in patients with coronary heart disease:
      longitudinal data from the Heart and Soul Study.
AB  - BACKGROUND: Statins are among the most commonly prescribed medications worldwide.
      Although their benefits for cardiovascular disease are well established, the
      effects of statins on depressive symptoms are unknown. METHOD: We examined the
      association between baseline statin use (2000-2002) and subsequent depressive
      symptoms in a prospective cohort study of 965 outpatients with coronary disease
      from 12 outpatient clinics in the San Francisco Bay Area. Depressive symptoms
      were assessed annually for 6 years using the Patient Health Questionnaire (PHQ)
      (primary outcome measure). We evaluated the cross-sectional association between
      statin use and risk of depressive symptoms at baseline and the longitudinal
      association between baseline statin use and risk of depressive symptoms during
      follow-up. RESULTS: Of the 965 participants, 629 (65%) used statins. At baseline,
      statin users had lower mean +/- SE PHQ depression scores than nonusers (4.8 +/-
      0.2 vs 5.9 +/- 0.3, P < .01). Statin users were less likely than nonusers to have
      depression (PHQ score >= 10) at baseline (17% vs 24%; P = .02) and during follow
      up (28% vs 40%; P < .01). Among the 776 patients without depressive symptoms at
      baseline (PHQ < 10), statin use was associated with a 48% decreased odds of
      developing depression during follow-up (odds ratio [OR], 0.52; 95% CI, 0.38-0.73;
      P < .01). After we adjusted for potentially confounding variables, statin use
      remained associated with a 38% decreased odds of subsequent depression (adjusted
      OR, 0.62; 95% CI, 0.41-0.95; P = .02). CONCLUSIONS: We found that statin use was
      associated with a decreased risk of subsequent depressive symptoms in patients
      with coronary heart disease. Whether use of statins prevents depressive symptoms
      deserves further study.

PMID- 22394434
TI  - Single vs. swarm detection of microparticles and exosomes by flow cytometry.
AB  - BACKGROUND: Microparticles and exosomes are cell-derived vesicles and potential
      biomarkers for disease. Recently, the Scientific Standardization Committee
      collaborative workshop of the ISTH initiated standardization of vesicle detection
      by flow cytometry with polystyrene beads. Because polystyrene beads have
      different optical properties from biological vesicles, and because the mechanisms
      causing the detection signal are incompletely understood, there are
      contradictions between expected and observed results. OBJECTIVES: To develop a
      model with which to relate the detection signal of a flow cytometer to the
      diameter of vesicles and clarify observed discrepancies. METHODS: We combined
      measurements of polystyrene and silica beads with an estimated refractive index
      of vesicles and performed Mie calculations of light scattering. RESULTS: We
      established the relationship between measured light scattering and the diameter
      of vesicles. The Megamix gating strategy proposed by the Scientific
      Standardization Committee selects single vesicles and cells with diameters
      between 800 and 2400 nm when applied on the forward-scattering detector of
      regular flow cytometers. Nevertheless, we demonstrated that, irrespective of the
      applied gating, multiple vesicles smaller than 220 nm or multiple 89-nm silica
      beads were counted as a single event signal at sufficiently high concentrations.
      CONCLUSIONS: Vesicle detection by flow cytometry is attributed to large single
      vesicles and swarm detection of smaller vesicles; that is, multiple vesicles are
      simultaneously illuminated by the laser beam and counted as a single event
      signal. Swarm detection allows the detection of smaller vesicles than previously
      thought possible, and explains the finding that flow cytometry underestimates the
      concentration of vesicles.

PMID- 22394435
TI  - Attachment and callous-unemotional traits in children with early-onset conduct
      problems.
AB  - BACKGROUND: Antisocial children with callous-unemotional (CU) traits appear to be
      disconnected from other people's emotions; although little is known about their
      experience of the parent-child emotional bond. This study examined parent-child
      attachment relationships and levels of CU traits in conduct-problem children.
      METHOD: Attachment classifications in boys (M = 6.31 years) with disruptive
      behaviour disorders were assessed using the Manchester Child Attachment Story
      Task. Multiple informants rated children's CU traits. RESULTS: Independent of
      severity of conduct problems, high levels of CU traits were associated with more
      insecure attachment; specifically, disorganised attachment representations;
      however, CU traits were not associated with avoidant representations.
      CONCLUSIONS: Among conduct-problem children, those higher on CU traits appear to
      be at increased risk of experiencing disruptions in parent-child attachment
      relationships; attachment may be an important area for treatment and prevention
      efforts for CU traits in young children.

PMID- 22394436
TI  - DNA methyltransferase 3B expression is associated with poor outcome of stage I
      testicular seminoma.
AB  - AIMS:   To examine in testicular seminomas the expression of DNA
      methyltransferase 3B (DNMT3B), which is known to be associated with early
      embryonic development and carcinogenesis, and to obtain a predictive marker for
      relapse of stage I seminomas. METHODS AND RESULTS:   Immunohistochemical
      examination of DNMT3B was performed in 88 cases of seminoma, 35 (39.8%) of which
      showed widely scattered nuclear immunoreactivity for DNMT3B, and 53 (60.2%) of
      which were completely negative. The incidence of focal DNMT3B expression was
      higher in stage III seminomas (5/5, 100%) than in stage I (25/70, 35.7%) or stage
      II (5/13, 38.5%) seminomas (P = 0.011). In stage I seminomas there were no
      significant correlations between DNMT3B expression and tumour size, invasion of
      the rete testis, or lymphatic or vascular involvement. Six of 25 cases (24%)
      showing DNMT3B expression relapsed, whereas only 3/45 cases (6.7%) lacking such
      expression did so (P = 0.037). Patients with seminomas showing DNMT3B expression
      had a significantly lower relapse-free survival rate than patients whose tumours
      lacked this feature (P = 0.0464). CONCLUSIONS:   Patients with seminomas showing
      focal DNMT3B expression are at increased risk of relapse, and should be followed
      up carefully.

PMID- 22394437
TI  - Ocean waves and roadside spirits: Thai health service providers' post-tsunami
      psychosocial health.
AB  - A massive earthquake off the west coast of Sumatra in Indonesia triggered a
      tsunami on 26 December 2004. At least five million people around the world were
      affected, and the total number of deaths exceeded 280,000. In Thailand, the
      tsunami struck six southern provinces, where the disaster's immediate impact was
      catastrophic. Based on ethnographic fieldwork in Phang Nga Province (2007), this
      paper provides an overview of the disaster's psychosocial consequences for Thai
      health service providers, the vast majority of whom were bypassed by regional
      post-tsunami mental health initiatives. The available tsunami literature only
      briefly attends to health providers' experience of professional 'burn-out',
      rather than explores the tsunami's wide spectrum of psychosocial effects. This
      research aims to remedy such oversights through 'critical medical' and
      'interpretive phenomenological' analysis of the diverse and culturally-situated
      ways in which health providers' experienced the tsunami. The paper concludes by
      arguing for disaster-related psychosocial interventions to involve health
      providers explicitly.

PMID- 22394438
TI  - [Cortisol and Cushing's syndrome].

PMID- 22394439
TI  - [Acute otitis media: do not change the Dutch practice guideline].
AB  - Two recent clinical trials have again shown that antibiotics are effective in the
      management of young children with acute otitis media (AOM). Should this change
      our reserved attitude towards the use of antibiotics? According to the rules for
      evidence-based medicine, we cannot ignore the vast body of evidence already
      existing unless new trials are methodologically better and their results differ
      from previous trials. This does not seem to be the case. The patient
      characteristics of these trials are similar to those of a previously published
      individual patient data meta-analysis. The primary outcome 'symptom scores'
      reported by Hoberman et al. is also comparable, but Tahtinen et al. may have
      overestimated the effect of antibiotics. Their primary outcome 'time to treatment
      failure' does not take later improvement or recovery into account. In both
      trials, the greatest benefit is related to otoscopic recovery of AOM, which is
      clinically not the most relevant outcome. For now, there is no reason to adapt
      the current AOM practice guideline of the Dutch College of General Practitioners.

PMID- 22394440
TI  - [New class of medicines for chronic hepatitis C].
AB  - Worldwide approximately 130-210 million people suffer from chronic hepatitis C.
      Adequate antiviral therapy reduces morbidity and mortality caused by chronic
      hepatitis C and prevents further spread of the hepatitis C-virus (HCV). The
      current standard treatment of chronic hepatitis C, consisting of the combination
      of pegylated interferon-alpha (peginterferon) and ribavirin, lasts 24-48 weeks,
      and is accompanied by significant side effects and has a suboptimal chance of
      success. Protease inhibitors, which have recently been registered, belong to a
      new class of medicines which directly affect the life cycle of HCV. Protease
      inhibitors, in combination with peginterferon and ribavirin, provide almost
      double the chance of curing in patients with HCV genotype 1. Treatment duration
      can be shortened in a considerable proportion of these patients. Since treatment
      with protease inhibitors can lead to resistant virus strains and this therapy
      leads to additional side effects, the complexity of treatment will increase.

PMID- 22394441
TI  - [Acute otitis media: do not hesitate to treat].
AB  - Recently, two randomised, double-blind, placebo-controlled trials published in
      The New England Journal of Medicine have stirred up discussion about the use of
      antibiotics in the treatment of acute otitis media (AOM). In the Netherlands, the
      practice guideline of the Dutch College of General Practitioners recommends
      withholding antibiotics in most cases and that antibiotics can be considered when
      a child under the age of 2 years has bilateral AOM, otorrhoea, or persistent
      symptoms for 3 days or more. These recommendations are mostly based on a meta
      analysis published in 2006. Previous studies on AOM had important limitations
      such as varying diagnostic criteria and biased patient selection. The new trials,
      which are of high methodological quality, investigated only 'real' AOM and the
      results show the same efficacy as the aforementioned meta-analysis. We therefore
      feel it is justified to consider prescribing antibiotics for a young child with
      manifest symptoms and evident AOM on otoscopic examination.

PMID- 22394442
TI  - [Preserving life and limb on the stage of death: the Dance of Death by Dr Salomon
      van Rusting].
AB  - Salomon van Rusting was a medical doctor from Amsterdam who lived and worked
      around the early 1700 s. He wrote one of the few Dutch Death Dances, naming it
      'Het Schouw-Tooneel des Doods'. A Death Dance was an artistic expression of human
      death popular in the Late Middle Ages. The traditional Death Dance invited
      acknowledgement of the vanity of worldly existence ('memento mori') by portraying
      human subjects' encounters with 'Death'. This paper describes the context in
      which Van Rusting's work arose and briefly characterizes its highly original and,
      for the most part, rather burlesque nature. In contrast to other Death Dances,
      Van Rusting's work does not represent medicine as being powerless in the face of
      death. His work strikes us as having almost modern confidence in our own ability
      to avoid an untimely death by living sensibly.

PMID- 22394443
TI  - [Conradi-Hunermann-Happle syndrome].
AB  - BACKGROUND: Conradi-Hunermann-Happle syndrome is caused by a mutation in the
      emopanil binding protein-gene (EBP), which encodes the enzyme 3beta
      hydroxysteroid-dehydrogenase-delta8,7 isomerase. This gene is involved in
      cholesterol metabolism. CASE DESCRIPTION: In this case report we describe a girl
      aged 19 months with Conradi-Hunermann-Happle syndrome. This syndrome was
      characterized in this patient by a complete erythrodermia directly after birth,
      followed by linear ichthyosis, shortened upper arms and thighs, vertebral
      anomalies resulting in progressive scoliosis and cataract. The patient's mother
      was found also to suffer from the Conradi-Hunermann-Happle syndrome. As a child
      she had linear ichthyosis, difference in leg length and congenital alopecia in a
      linear pattern. CONCLUSION: For diagnosis and treatment of children with such a
      rare syndrome a multidisciplinary approach is essential. Multidisciplinary
      collaboration guarantees an appropriate follow-up for the patient and the family.

PMID- 22394444
TI  - [Ultrasonically guided breast-conserving surgery for palpable mammary tumours].
AB  - Breast-conserving surgery for palpable mammary tumours is usually guided by
      palpation. It appears, however, that identifying tumour margins only by palpation
      can be problematic, resulting in less than optimal effectiveness of this type of
      operation. The use of ultrasonography is a simple and non-invasive way of
      facilitating real-time localisation of breast carcinoma during surgery so that a
      tumour can be excised with controlled precision. Ultrasound is used to localise
      the tumour prior to surgery; its location is subsequently marked on the skin.
      During tissue dissection, ultrasound can be used to inspect the location and
      depth of the tumour as well as determining whether the tumour's surrounding
      margins are sufficient, thereby preventing the unnecessary removal of healthy
      tissue. Ultrasound can be used again after the excision to verify that the tumour
      was indeed radically removed. The efficacy of ultrasonically guided surgery for
      palpable mammary tumours is currently being studied in a prospective, randomised,
      multicentre trial.

PMID- 22394445
TI  - [Ketamine-associated urological symptoms].
AB  - Ketamine is used as an anaesthetic and in third-line pain management.
      Furthermore, recreational use of the drug is becoming increasingly popular due to
      its dissociative and hallucinogenic effects. Ketamine can affect the urothelium,
      possibly with long-term damage to the bladder and kidneys. An otherwise healthy,
      22-year-old female smoker was referred to our clinic. Shortly after starting
      recreational ketamine she experienced gross haematuria, urgency, frequency and
      dysuria. There had been no febrile episodes or flank pain. Her urine cultures
      were sterile. Physical examination, blood tests, urinary cytology and abdominal
      ultrasound results were normal. A severely inflamed bladder was seen during
      cystoscopy. Biopsies showed denuded urothelium and inflammation of the submucosa
      without malignancy. The precise mechanism of ketamine-associated urological
      symptoms is currently unknown. Treatment, therefore, is symptom-targeted and
      cessation of ketamine is imperative. We recommend that ketamine use is considered
      in patients with otherwise unexplained urological symptoms.

PMID- 22394447
TI  - [Patients expect antibiotics. Or not? A folie a deux].
AB  - Doctors often feel pressured by patients to prescribe antibiotics for a common
      cold or a sore throat, against their better judgment. Yet do patients really put
      pressure on their doctor or even expect a prescription for an antibiotic or some
      other medicine? Several interesting studies shed some light on this issue.
      Doctors in an emergency department, for example, prescribed an antibiotic much
      more frequently than their patients expected them to. Only in 25% of cases were
      the doctors correct in their assumptions about patient expectations. In a
      Norwegian study, the authors found that parents wanted more time and explanation
      for their coughing children and fewer prescriptions. So instead of assuming that
      patients want antibiotics for innocent symptoms, we should put more effort into
      exploring patients' expectations and providing them with relevant information.
      That way we can step out of the folie a deux.

PMID- 22394448
TI  - A unified procedure for meta-analytic evaluation of surrogate end points in
      randomized clinical trials.
AB  - The meta-analytic approach to evaluating surrogate end points assesses the
      predictiveness of treatment effect on the surrogate toward treatment effect on
      the clinical end point based on multiple clinical trials. Definition and
      estimation of the correlation of treatment effects were developed in linear mixed
      models and later extended to binary or failure time outcomes on a case-by-case
      basis. In a general regression setting that covers nonnormal outcomes, we discuss
      in this paper several metrics that are useful in the meta-analytic evaluation of
      surrogacy. We propose a unified 3-step procedure to assess these metrics in
      settings with binary end points, time-to-event outcomes, or repeated measures.
      First, the joint distribution of estimated treatment effects is ascertained by an
      estimating equation approach; second, the restricted maximum likelihood method is
      used to estimate the means and the variance components of the random treatment
      effects; finally, confidence intervals are constructed by a parametric bootstrap
      procedure. The proposed method is evaluated by simulations and applications to 2
      clinical trials.

PMID- 22394449
TI  - Molecular diagnosis of African Swine Fever by a new real-time PCR using universal
      probe library.
AB  - A highly sensitive and specific real-time PCR method was developed for the
      reliable and rapid detection of African swine fever virus (ASFV). The method uses
      a commercial Universal Probe Library (UPL) probe combined with a specifically
      designed primer set to amplify an ASFV DNA fragment within the VP72 coding genome
      region. The detection range of the optimized UPL PCR technique was confirmed by
      analysis of a large panel (n = 46) of ASFV isolates, belonging to 19 of the 22
      viral p72 genotypes described. No amplification signal was observed when closely
      clinically related viruses, such as classical swine fever, or other porcine
      pathogens were tested by this assay. The detection limit of the UPL PCR method
      was established below 18 DNA copies. Validation experiments using an extensive
      collection of field porcine and tick samples (n = 260), coming from Eastern and
      Western African regions affected by ASF, demonstrated that the UPL PCR technique
      was able to detect over 10% more positive samples than the real-time TaqMan PCR
      test recommended in the OIE manual, confirming its superior diagnostic
      sensitivity. Clinical material collected during experimental infections with
      different ASFV p72 genotypes was useful for assuring both the capacity of the UPL
      PCR for an early viral DNA detection and the competence of the technique to be
      applied in any ASF diagnostic target sample. The reliability and robustness of
      the UPL PCR was finally verified with a panel of ASFV-infected clinical samples
      which was repeatedly tested at different times. Additionally, an internal control
      PCR assay was also developed and standardized using UPL probes within the
      endogenous beta-actin gene. Finally, the complete study offers a new validated
      real-time PCR technique, by means of a standardized commercial probe, providing a
      simple, rapid and affordable test, which is ready for application in the routine
      diagnosis of ASF.

PMID- 22394450
TI  - The structure of Ca2+-loaded S100A2 at 1.3-A resolution.
AB  - S100A2 is an EF-hand calcium ion (Ca(2+))-binding protein that activates the
      tumour suppressor p53. In order to understand the molecular mechanisms underlying
      the Ca(2+) -induced activation of S100A2, the structure of Ca(2+)-bound S100A2
      was determined at 1.3 A resolution by X-ray crystallography. The structure was
      compared with Ca(2+) -free S100A2 and with other S100 proteins. Binding of Ca(2+)
      to S100A2 induces small structural changes in the N-terminal EF-hand, but a large
      conformational change in the C-terminal EF-hand, reorienting helix III by
      approximately 90 degrees . This movement is accompanied by the exposure of a
      hydrophobic cavity between helix III and helix IV that represents the target
      protein interaction site. This molecular reorganization is associated with the
      breaking and new formation of intramolecular hydrophobic contacts. The target
      binding site exhibits unique features; in particular, the hydrophobic cavity is
      larger than in other Ca(2+)-loaded S100 proteins. The structural data underline
      that the shape and size of the hydrophobic cavity are major determinants for
      target specificity of S100 proteins and suggest that the binding mode for S100A2
      is different from that of other p53-interacting S100 proteins. Database
      Structural data are available in the Protein Data Bank database under the
      accession number 4DUQ

PMID- 22394451
TI  - U(VI) sorption and reduction kinetics on the magnetite (111) surface.
AB  - Sorption of contaminants onto mineral surfaces is an important process that can
      restrict their transport in the environment. In the current study, uranium (U)
      uptake on magnetite (111) was measured as a function of time and solution
      composition (pH, [CO(3)](T), [Ca]) under continuous batch-flow conditions. We
      observed, in real-time and in situ, adsorption and reduction of U(VI) and
      subsequent growth of UO(2) nanoprecipitates using atomic force microscopy (AFM)
      and newly developed batch-flow U L(III)-edge grazing-incidence X-ray absorption
      spectroscopy near-edge structure (GI-XANES) spectroscopy. U(VI) reduction
      occurred with and without CO(3) present, and coincided with nucleation and growth
      of UO(2) particles. When Ca and CO(3) were both present no U(VI) reduction
      occurred and the U surface loading was lower. In situ batch-flow AFM data
      indicated that UO(2) particles achieved a maximum height of 4-5 nm after about 8
      h of exposure, however, aggregates continued to grow laterally after 8 h reaching
      up to about 300 nm in diameter. The combination of techniques indicated that U
      uptake is divided into three-stages; (1) initial adsorption of U(VI), (2)
      reduction of U(VI) to UO(2) nanoprecipitates at surface-specific sites after 2-3
      h of exposure, and (3) completion of U(VI) reduction after ~6-8 h. U(VI)
      reduction also corresponded to detectable increases in Fe released to solution
      and surface topography changes. Redox reactions are proposed that explicitly
      couple the reduction of U(VI) to enhanced release of Fe(II) from magnetite.
      Although counterintuitive, the proposed reaction stoichiometry was shown to be
      largely consistent with the experimental results. In addition to providing
      molecular-scale details about U sorption on magnetite, this work also presents
      novel advances for collecting surface sensitive molecular-scale information in
      real-time under batch-flow conditions.

PMID- 22394453
TI  - There is insufficient evidence to recommend lens extraction as a treatment for
      primary open-angle glaucoma: an evidence-based perspective--comment.

PMID- 22394454
TI  - Specific IgE measurement using AdvanSure(r) system: comparison of detection
      performance with ImmunoCAP(r) system in Korean allergy patients.
AB  - BACKGROUND: AdvanSure enzyme immunoassay (EIA) system is a recently developed
      multiple allergen screen test with specific immunoglobulin E (sIgE) detection
      assay, while ImmunoCAP fluorescent EIA (FEIA) has been widely used for sIgE
      detection. There has been no inter-assay comparison data for these two systems.
      We determined the detection performance of AdvanSure system compared to that of
      ImmunoCAP. METHODS: We performed an inter-method comparison using sera from 199
      Korean allergy patients, including asthma (39.7%), allergic rhinitis (54.8%),
      atopic dermatitis (36.2%) and food allergies (21.6%). We compared the sIgE
      detection performance for nine major inhalant and four food allergens. RESULTS:
      950 paired assay results were analyzed. Most allergen sIgE results showed above
      0.5 intraclass correlation coefficient except Blattella germanica, alternaria and
      mugwort allergen. Intermethod comparison results showed multiple differences in a
      few allergens. The inter-method concordance was moderate to substantial for most
      allergens (kappa=0.528-0.778, p<0.001), except for cat dander. CONCLUSION:
      AdvanSure system showed a good detection performance compared with ImmunoCAP in
      correlation and agreement in Korean allergy patients. However, in terms of
      differences in the methodologies used by these two systems, careful clinical
      correlation is needed for interpretation of AdvanSure EIA results.

PMID- 22394452
TI  - Developmental allometry and paediatric malaria.
AB  - WHO estimates that 80% of mortality due to malaria occurs among infants and young
      children. Though it has long been established that malaria disproportionately
      affects children under age five, our understanding of the underlying biological
      mechanisms for this distribution remains incomplete. Many studies use age as an
      indicator of exposure, but age may affect malaria burden independently of
      previous exposure. Not only does the severity of malaria infection change with
      age, but the clinical manifestation of disease does as well: younger children are
      more likely to suffer severe anaemia, while older children are more likely to
      develop cerebral malaria. Intensity of transmission and acquired immunity are
      important determinants of this age variation, but age differences remain
      consistent over varying transmission levels. Thus, age differences in clinical
      presentation may involve inherent age-related factors as well as still
      undiscovered facets of acquired immunity, perhaps including the rates at which
      relevant aspects of immunity are acquired. The concept of "allometry" - the
      relative growth of a part in relation to that of an entire organism or to a
      standard - has not previously been applied in the context of malaria infection.
      However, because malaria affects a number of organs and cells, including the
      liver, red blood cells, white blood cells, and spleen, which may intrinsically
      develop at rates partly independent of each other and of a child's overall size,
      developmental allometry may influence the course and consequences of malaria
      infection. Here, scattered items of evidence have been collected from a variety
      of disciplines, aiming to suggest possible research paths for investigating
      exposure-independent age differences affecting clinical outcomes of malaria
      infection.

PMID- 22394455
TI  - Simultaneous quantification of nicotine, cotinine, trans-3'-hydroxycotinine,
      norcotinine and mecamylamine in human urine by liquid chromatography-tandem mass
      spectrometry.
AB  - BACKGROUND: Mecamylamine is a nicotine antagonist under investigation in
      combination with nicotine replacement for smoking treatment. METHODS: A simple,
      rapid and reliable liquid chromatography tandem mass spectrometry (LCMSMS) method
      was developed and validated for quantifying nicotine, cotinine, trans-3'
      hydroxycotinine, norcotinine and mecamylamine in human urine. Chromatography was
      performed on a Synergi PolarRP column with a gradient of 0.1% formic acid and
      0.1% formic acid in acetonitrile at 0.25 ml/min with an 8-min total runtime.
      Analytes were monitored by positive mode electrospray ionization and multiple
      reaction monitoring mass spectrometry. RESULTS: Linear dynamic ranges were 1-500
      ng/ml for nicotine and norcotinine, 0.5-500 ng/ml for trans-3'-hydroxycotinine,
      0.2-500 ng/ml for cotinine, and 0.1-100 ng/ml for mecamylamine; correlation
      coefficients were consistently greater than 0.99, and all calibrator
      concentrations were within 20% of target. Extensive endogenous and exogenous
      interferences were evaluated. At 3 concentrations spanning the linear dynamic
      range of the assay, mean extraction efficiencies from urine were 55.1-109.1% with
      analytical recovery (bias) 82.0-118.7% and total imprecision of 0.7-9.1%.
      Analytes were stable for 24h at room temperature, 72 h at 4  degrees C, 72 h in
      autosampler at 15  degrees C and after three freeze/thaw cycles. CONCLUSION: This
      method is useful for monitoring mecamylamine, nicotine and nicotine metabolites
      in smoking cessation and other clinical nicotine research.

PMID- 22394456
TI  - Immunoadjuvant activity, toxicity assays, and determination by UPLC/Q-TOF-MS of
      triterpenic saponins from Chenopodium quinoa seeds.
AB  - The adjuvant activity of Chenopodium quinoa (quinoa) saponins on the humoral and
      cellular immune responses of mice subcutaneously immunized with ovalbumin (OVA)
      was evaluated. Two quinoa saponin fractions were obtained, FQ70 and FQ90, and 10
      saponins were determined by UPLC/Q-TOF-MS. Mice were immunized subcutaneously
      with OVA alone or adjuvanted with Quil A (adjuvant control), FQ70, or FQ90. FQ70
      and FQ90 significantly enhanced the amount of anti-OVA-specific antibodies in
      serum (IgG, IgG1, and IgG2b) in immunized mice. The adjuvant effect of FQ70 was
      significantly greater than that of FQ90. However, delayed type hypersensitivity
      responses were higher in mice immunized with OVA adjuvanted with FQ90 than mice
      treated with FQ70. Concanavalin A (Con A)-, lipopolysaccharide-, and OVA
      stimulated splenocyte proliferation were measured, and FQ90 significantly
      enhanced the Con A-induced splenocyte proliferation. The results suggested that
      the two quinoa saponin fractions enhanced significantly the production of humoral
      and cellular immune responses to OVA in mice.

PMID- 22394457
TI  - Continued cannabis use and outcome in first-episode psychosis: data from a
      randomized, open-label, controlled trial.
AB  - OBJECTIVE: Cannabis use has been found to increase the risk of psychosis. It is
      unclear whether, after a first psychotic episode has occurred, continued cannabis
      use is associated with poor functional outcome of psychosis. METHOD: As part of a
      randomized, open-label, controlled trial, the association of cannabis use and
      measures for psychopathology and social role functioning after 2 years of follow
      up and for the recently proposed outcome measures of symptomatic remission,
      functional remission, and clinical recovery was explored in a group of 124
      patients suffering from nonaffective first-episode psychosis (diagnosed according
      to DSM-IV and included from a catchment area in the Netherlands of 3.1 million
      inhabitants from October 2001 through December 2002). Other patient
      characteristics that were expected to be independently associated with outcome,
      among them alcohol and other drug use, were assessed at baseline. RESULTS:
      Continued cannabis use was not associated with symptomatic or functional
      remission or clinical recovery. After 2 years, cannabis use was related to
      certain aspects of social role functioning (economic and social activities;
      explained variance 5.6% and 8.4%, respectively) but not to psychopathology
      (Positive and Negative Syndrome Scale Positive, Negative, or General symptoms).
      CONCLUSIONS: Our findings support the notion that continued cannabis use after
      the onset of a first-episode psychosis is correlated with worse social outcome
      and should be discouraged whenever possible, but its role in outcome is modest in
      comparison to other factors. TRIAL REGISTRATION: Nederlands Trial Register:
      http://www.trialregister.nl (ID: NTR 374).

PMID- 22394458
TI  - Development of a fast PCR protocol enabling rapid generation of AmpFlSTR(r)
      Identifiler(r) profiles for genotyping of human DNA.
AB  - BACKGROUND: Traditional PCR methods for forensic STR genotyping require
      approximately 2.5 to 4 hours to complete, contributing a significant portion of
      the time required to process forensic DNA samples. The purpose of this study was
      to develop and validate a fast PCR protocol that enabled amplification of the 16
      loci targeted by the AmpFlSTR(r) Identifiler(r) primer set, allowing decreased
      cycling times. METHODS: Fast PCR conditions were achieved by substituting the
      traditional Taq polymerase for SpeedSTARTM HS DNA polymerase which is designed
      for fast PCR, by upgrading to a thermal cycler with faster temperature ramping
      rates and by modifying cycling parameters (less time at each temperature) and
      adopting a two-step PCR approach. RESULTS: The total time required for the
      optimized protocol is 26 min. A total of 147 forensically relevant DNA samples
      were amplified using the fast PCR protocol for Identifiler. Heterozygote peak
      height ratios were not affected by fast PCR conditions, and full profiles were
      generated for single-source DNA amounts between 0.125 ng and 2.0 ng. Individual
      loci in profiles produced with the fast PCR protocol exhibited average n-4
      stutter percentages ranging from 2.5 +/- 0.9% (THO1) to 9.9 +/- 2.7% (D2S1338).
      No increase in non-adenylation or other amplification artefacts was observed.
      Minor contributor alleles in two-person DNA mixtures were reliably discerned. Low
      level cross-reactivity (monomorphic peaks) was observed with some domestic animal
      DNA. CONCLUSIONS: The fast PCR protocol presented offers a feasible alternative
      to current amplification methods and could aid in reducing the overall time in
      STR profile production or could be incorporated into a fast STR genotyping
      procedure for time-sensitive situations.

PMID- 22394459
TI  - Time-dependent changes of myeloperoxidase in relation to in-hospital mortality in
      patients with the first anterior ST-segment elevation myocardial infarction
      treated by primary percutaneous coronary intervention.
AB  - OBJECTIVES: To analyze the prognostic value of myeloperoxidase (MPO) in relation
      to in-hospital mortality and to identify the optimum time point for sampling in
      patients with the first anterior ST-segment elevation myocardial infarction
      (STEMI) treated by primary percutaneous coronary intervention (pPCI). DESIGN AND
      METHODS: A total of 100 consecutive patients with the first anterior STEMI
      undergoing pPCI were included. Blood samples were collected at baseline, 4, 8,
      12, 18, 24, 48 and 168 hours (h) after pPCI. RESULTS: MPO concentrations have
      showed a biphasic pattern over time; the highest MPO levels were at4h and 24h
      after pPCI. In-hospital mortality was 6%. MPO at 24h significantly correlated
      with troponin I as well as heart failure. After multivariate adjustment, MPO at
      24h was an independent predictor of the in-hospital mortality (OR 3.34, 95% CI
      1.13-9.86, P=0.029). CONCLUSIONS: In patients with the first anterior STEMI
      treated by pPCI, MPO at 24h after procedure was an independent predictor of the
      in-hospital mortality.

PMID- 22394460
TI  - Cystatin C as a predictor of all-cause mortality and myocardial infarction in
      patients with non-ST-elevation acute coronary syndrome.
AB  - OBJECTIVES: To investigate the predictive value of cystatin C among patients
      diagnosed with non-ST-elevation acute coronary syndrome (nSTE-ACS). DESIGN AND
      METHODS: Admission serum samples from 245 nSTE-ACS patients were measured with a
      novel cystatin C immunoassay based on a dry-reagent, double monoclonal design.
      Creatinine concentrations, estimated glomerular filtration rates (eGFR) and one
      year follow-up data were available for these patients. RESULTS: During the follow
      up period, 34 (14%) of patients had myocardial infarction (MI) and 25 (11%) died.
      Increased serum cystatin C was an independent predictor of all-cause mortality
      and combined events (all-cause mortality and MI) after adjustment to non
      biomarker baseline factors, hazard ratio (HR) 2.19 (per increase of 1 tertile;
      95% Cl 1.28-3.78, p=0.0046) and 1.75 (1.22-2.51, p=0.0024), respectively.
      Corresponding values for eGFR were 2.56 (1.43-4.59, p=0.0016) and 1.76 (1.23
      2.53, p=0.0022), respectively. Creatinine was not an independent predictor of
      endpoints (p>0.05). CONCLUSIONS: Cystatin C was associated with an increased risk
      of death and combined events in patients with nSTE-ACS.

PMID- 22394461
TI  - EN-RAGE (extracellular newly identified receptor for advanced glycation end
      products binding protein) and mortality of long-term hemodialysis patients: A
      prospective observational cohort study.
AB  - OBJECTIVES: EN-RAGE is extracellular newly identified receptor for advanced
      glycation end-products binding protein playing a role in inflammation. The aim
      was to test the relationship of EN-RAGE to prognosis of long-term hemodialysis
      patients (HD). DESIGN AND METHODS: This is a prospective observational cohort
      study in 261 HD patients followed up for five years. Laboratory parameters were
      measured at the beginning of the study. RESULTS: EN-RAGE was slightly but
      unsignificantly increased in HD patients compared with healthy controls and
      correlated significantly with inflammatory markers. Univariate Cox analysis
      demonstrated EN-RAGE as a significant predictor for mortality due to infection
      (HR (95%CI): 1.305 (1.063-1.602), per standard deviation, p=0.01), but this
      significance disappeared in multivariate Cox analysis when CRP was included into
      the model. CONCLUSIONS: Our study demonstrates EN-RAGE as an inflammatory
      biomarker. It is related to mortality of HD patients due to infection, but in our
      study, it did not provide additional information to CRP.

PMID- 22394462
TI  - An integrated system for monitoring the quality of sample transportation.
AB  - OBJECTIVES: Due to the consolidation of laboratory testing facilities, there is
      an increasing need for systems able to assure quality and safety in biological
      sample transportation, although little evidence on this aspect is available in
      literature. DESIGN AND METHODS: An integrated system for sample transportation,
      implemented and monitored over a five-year period by our team, consists of
      secondary and tertiary containers, a device for temperature and time recording,
      and a system manager allowing the acceptance or rejection of biological samples
      through the immediate visualization and validation of registered data. RESULTS:
      Data collected between 2009 and October 2011, after a preliminary phase for
      optimizing the temperature inside the containers, demonstrated the frequency of
      transportations at an acceptable temperature (<20  degrees C) had increased and
      that of transportations at an excessively high temperature (>25  degrees C) had
      decreased by ~80%. CONCLUSIONS: The integrated system and related operating
      instructions allow improvement in the quality of sample transportation over time.

PMID- 22394463
TI  - RASSF1A Ala133Ser polymorphism is associated with increased susceptibility to
      hepatocellular carcinoma in a Turkish population.
AB  - AIM: The tumor suppressor gene Ras association domain family 1 isoform A
      (RASSF1A) regulates cell cycle regulation, apoptosis and microtubule stability
      and is inactivated by promoter hypermethylation at a high frequency in
      hepatocellular carcinoma (HCC). A guanine (G)/thymine (T) common single
      nucleotide polymorphism (SNP) at first position of codon 133 in RASSF1A gene
      determines an alanine (Ala) to serine (Ser) (Ala133Ser) amino acidic substitution
      which may alter cancer risk by influencing the function of RASSF1A protein.
      METHODS: To determine the association of the RASSF1A Ala133Ser polymorphism with
      the risk of HCC development in a Turkish population, a hospital-based case
      control study was designed consisting of 236 subjects with HCC and 236 cancer
      free control subjects matched for age, gender, smoking and alcohol status. The
      genotype frequency of the RASSF1A Ala133Ser polymorphism was determined by using
      a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      assay. RESULTS: Allele and genotype associations of RASSF1A Ala133Ser
      polymorphism with HCC susceptibility were observed in comparisons between the
      patient and control samples (P<0.001). Risk of HCC development in this Turkish
      population was significantly increased in carriers of the Ser133 variant allele
      of Ala133Ser polymorphism (Ala/Ser and Ser/Ser genotypes) when compared with
      homozygote Ala/Ala genotype (OR=5.47, 95% CI=3.63-8.25, P=0.001). CONCLUSION:
      Because our results suggest for the first time that the Ser133 allele of RASSF1A
      Ala133Ser polymorphism may be a genetic susceptibility factor for HCC in the
      Turkish population, further independent studies are required to validate our
      findings in a larger series, as well as in patients of different ethnic origins.

PMID- 22394464
TI  - Is there benefit in optimising heart failure treatment in over-80 year-old
      patients? (HF-80 study): study protocol for a randomized controlled trial.
AB  - BACKGROUND: An aging population and better management of various heart diseases
      explain the exponential growth in incidence and prevalence of chronic heart
      failure, with poor prognosis and heavy health costs. Medical management is
      codified in international guidelines. The management of heart failure in over-80
      year-old patients follows these guidelines, but no clinical trials have been able
      to confirm benefit. Moreover, registries show down-prescription of heart failure
      treatments in the elderly and over-80s. METHODS/DESIGN: We present the design of
      the HF-80 ("Is there benefit in optimising heart failure treatment in over-80
      year-old patients?") study, which is a prospective randomised open-label clinical
      trial with blinded end-points, designed to evaluate the effect of optimising
      management by adhering to guidelines in over-80 year-old heart failure patients.
      Patients over 80 years of age admitted with acute heart failure will be included.
      The primary endpoint is to assess quality of life at 6 months on the Minnesota
      questionnaire. The secondary endpoints are to assess the effect of optimised
      management on quality of life, mortality, readmission for acute heart failure,
      cardiac fibrosis and economic data at 12 months. 80 patients will be included,
      divided into 2 groups: group A, with usual heart failure management by general
      practitioners; and group B, with optimised management based on international
      guidelines. DISCUSSION: It is necessary to assess the benefit of guidelines in
      over-80 year-old heart failure patients because of the fragility of this
      population and the elevated risk of iatrogenic complications. TRIAL REGISTRATION:
      Clinical trials.gov number: NCT01437371.

PMID- 22394465
TI  - The mutacins of Streptococcus mutans: regulation and ecology.
AB  - Streptococcus mutans is generally recognized as a causative agent of human dental
      caries. The production of mutacins (bacteriocins) by S. mutans is considered to
      be an important factor in the colonization and establishment of S. mutans in the
      dental biofilm. Two types of mutacins have been characterized: the lantibiotics
      and the non-lantibiotics. The lantibiotics generally have a wider spectrum of
      activity than the non-lantibiotics, which make them attractive targets for
      development into new antimicrobial modalities. The non-lantibiotics are much more
      prevalent among strains of S. mutans and play a significant role in both
      community-level and population-level interactions in the dental biofilm. These
      interactions are directly mediated through the ComCDE two-component system and
      the newly characterized LytTR Regulation Systems HdrRM and BrsRM. These systems
      coordinate natural competence development and mutacin production as a means to
      acquire transforming DNA either by killing closely related streptococcal species
      in the vicinity of S. mutans, or through an altruistic suicide mechanism among a
      subpopulation of competent cells within the S. mutans community. As more S.
      mutans strains are sequenced, it is anticipated that additional mutacins with
      novel functions will be discovered, which may yield further insights into the
      ecological role of mutacins within the oral biofilm.

PMID- 22394466
TI  - Lipopolysaccharides mediate leukotoxin secretion in Aggregatibacter
      actinomycetemcomitans.
AB  - We previously reported that lipopolysaccharide (LPS) -related sugars are
      associated with the glycosylation of the collagen adhesin EmaA, a virulence
      determinant of Aggregatibacter actinomycetemcomitans. In this study, the role of
      LPS in the secretion of other virulence factors was investigated. The secretion
      of the epithelial adhesin Aae, the immunoglobulin Fc receptor Omp34 and
      leukotoxin were examined in a mutant strain with inactivated TDP-4-keto-6-deoxy-d
      glucose 3,5-epimerase (rmlC), which resulted in altered O-antigen polysaccharides
      (O-PS) of LPS. The secretion of Aae and Omp34 was not affected. However, the
      leukotoxin secretion, which is mediated by the TolC-dependent type I secretion
      system, was altered in the rmlC mutant. The amount of secreted leukotoxin in the
      bacterial growth medium was reduced nine-fold, with a concurrent four-fold
      increase of the membrane-bound toxin in the mutant compared with the wild-type
      strain. The altered leukotoxin secretion pattern was restored to the wild-type by
      complementation of the rmlC gene in trans. Examination of the ltxA mRNA levels
      indicated that the leukotoxin secretion was post-transcriptionally regulated in
      the modified O-PS containing strain. The mutant strain also showed increased
      resistance to vancomycin, an antibiotic dependent on TolC for internalization,
      indicating that TolC was affected. Overexpression of TolC in the rmlC mutant
      resulted in an increased TolC level in the outer membrane but did not restore the
      leukotoxin secretion profile to the wild-type phenotype. The data suggest that O
      PS mediate leukotoxin secretion in A. actinomycetemcomitans.

PMID- 22394468
TI  - Identification of a functional capsule locus in Streptococcus mitis.
AB  - The polysaccharide capsule of Streptococcus pneumoniae is a hallmark for
      virulence in humans. In its close relative Streptococcus mitis, a common human
      commensal, analysis of the sequenced genomes of six strains revealed the presence
      of a putative capsule locus in four of them. We constructed an isogenic S. mitis
      mutant from the type strain that lacked the 19 open reading frames in the capsule
      locus (Deltacps mutant), using a deletion strategy similar to previous capsule
      functional studies in S. pneumoniae. Transmission electron microscopy and atomic
      force microscopy revealed a capsule-like structure in the S. mitis type strain
      that was absent or reduced in the Deltacps mutant. Since S. mitis are predominant
      oral colonizers of tooth surfaces, we addressed the relevance of the capsule
      locus for the S. mitis overall surface properties, autoaggregation and biofilm
      formation. The capsule deletion resulted in a mutant with approximately two-fold
      increase in hydrophobicity. Binding to the Stains-all cationic dye was reduced by
      40%, suggesting a reduction in the overall negative surface charge of the mutant.
      The mutant exhibited also increased autoaggregation in coaggregation buffer, and
      up to six-fold increase in biofilm levels. The results suggested that the capsule
      locus is associated with production of a capsule-like structure in S. mitis and
      indicated that the S. mitis capsule-like structure may confer surface attributes
      similar to those associated with the capsule in S. pneumoniae.

PMID- 22394467
TI  - CcpA regulates biofilm formation and competence in Streptococcus gordonii.
AB  - Streptococcus gordonii is an important member of the oral biofilm community. As
      an oral commensal streptococcus, S. gordonii is considered beneficial in
      promoting biofilm homeostasis. CcpA is known as the central regulator of carbon
      catabolite repression in Gram-positive bacteria and is also involved in the
      control of virulence gene expression. To further establish the role of CcpA as
      central regulator in S. gordonii, the effect of CcpA on biofilm formation and
      natural competence of S. gordonii was investigated. These phenotypic traits have
      been suggested to be important to oral streptococci in coping with environmental
      stress. Here we demonstrate that a CcpA mutant was severely impaired in its
      biofilm-forming ability, showed a defect in extracellular polysaccharide
      production and reduced competence. The data suggest that CcpA is involved in the
      regulation of biofilm formation and competence development in S. gordonii.

PMID- 22394469
TI  - Fusobacterium nucleatum GroEL induces risk factors of atherosclerosis in human
      microvascular endothelial cells and ApoE(-/-)  mice.
AB  - Infection and inflammation are risk factors in the initiation and progression of
      atherosclerosis. Periodontitis is one of the most prevalent chronic inflammations
      of the oral cavity, and has been reported to be associated with systemic disease.
      In this study, we evaluated whether the heat-shock protein GroEL of Fusobacterium
      nucleatum, one of the most prevalent bacteria in periodontitis, induces factors
      that predispose to atherosclerosis in human microvascular endothelial cells (HMEC
      1) and apolipoprotein E-deficient (ApoE(-/-)) mice. GroEL induced the expression
      of chemokines such as monocyte chemoattractant protein-1 and interleukin-8 as
      well as cell adhesion molecules, such as intercellular adhesion molecule 1,
      vascular cell adhesion molecule 1, and E-selectin. GroEL induced the activity of
      tissue factor and reduced the activity of the tissue factor pathway inhibitor.
      Foam cell formation was induced by GroEL. GroEL-injected ApoE(-/-) mice showed
      significant atherosclerotic lesion progression compared with control mice. Serum
      levels of risk factors for atherosclerosis such as interleukin-6, C-reactive
      protein, and low-density lipoprotein were increased in GroEL-injected ApoE(-/-)
      mice compared with control mice, whereas serum levels of high-density lipoprotein
      were decreased. We could detect significantly higher levels of anti-F. nucleatum
      GroEL antibody in serum and F. nucleatum DNA in gingival crevicular fluid from
      patients with periodontitis than in that from healthy subjects. Our results
      indicate that the host response to the GroEL of periodontal pathogens like F.
      nucleatum may be a mechanism involved in atherosclerosis, supporting the
      association of periodontitis and systemic infection.

PMID- 22394470
TI  - Association of CiaRH with resistance of Streptococcus mutans to antimicrobial
      peptides in biofilms.
AB  - Streptococcus mutans is a cariogenic pathogen in humans. To persist in the oral
      cavity, S. mutans is resistant against several antibacterial factors derived from
      the host. In this study, we investigated the mechanism of resistance to cationic
      antimicrobial peptides (AMPs), which are innate immune factors in humans. Because
      dltA-D (teichoic acid biosynthesis) was reported to affect the susceptibility to
      AMPs in other bacterial species, we evaluated the susceptibility of a dltC
      knockout mutant of S. mutans to the AMPs human beta-defensin-1 (hBD1), hBD2, hBD3
      and LL37. The dltC mutant exhibited significantly increased susceptibility to
      AMPs. Regulation of dltC expression involved CiaRH, a two-component system.
      Expression of dltC in the wild-type strain was significantly increased in biofilm
      cells compared with that in planktonic cells, whereas expression was not
      increased in a ciaRH knockout mutant. In biofilm cells, we found that
      susceptibility to LL37 was increased in the ciaRH mutant compared with that in
      the wild type. From these results, it is concluded that Dlt is involved in the
      susceptibility of S. mutans to AMPs and is regulated by CiaRH in biofilm cells.

PMID- 22394471
TI  - Evaluation of the glycine transporter inhibitor Org 25935 as augmentation to
      cognitive-behavioral therapy for panic disorder: a multicenter, randomized,
      double-blind, placebo-controlled trial.
AB  - OBJECTIVE: A growing body of evidence supports the efficacy of D-cycloserine
      (DCS), a partial agonist at the N-methyl-D-aspartate (NMDA) glutamate receptor,
      as augmentation to cognitive-behavioral therapy (CBT) in the treatment of anxiety
      disorders. Org 25935 is a glycine transporter 1 inhibitor that acts to increase
      synaptic glycine levels and enhance NMDA-mediated glutamatergic activity. The aim
      of this study was to examine the efficacy of a glutamatergic compound other than
      DCS in a CBT augmentation paradigm. METHOD: This was a randomized, double-blind,
      placebo-controlled, parallel-group clinical trial for which participants were
      recruited from November 2008 through February 2010. Eligible adult patients
      diagnosed (DSM-IV) with panic disorder with or without agoraphobia (N = 40) were
      scheduled to receive 5 manualized CBT treatment sessions. Participants were
      randomly assigned to receive either a dose of Org 25935 (4 mg or 12 mg) or
      placebo 2 hours prior to the start of CBT sessions 3, 4, and 5. The primary
      endpoint was symptomatic change as measured by the Panic Disorder Severity Scale
      (PDSS) 1 week following the last CBT session. RESULTS: Although mean PDSS total
      scores decreased significantly from baseline to end of treatment in every group,
      no statistically significant benefit was observed for Org 25935 (4 or 12 mg) over
      placebo on the primary endpoint or on any secondary efficacy endpoint. Org 25935
      showed no safety issues at either dose but was much better tolerated at the 4-mg
      dose level than at the 12-mg dose level. CONCLUSIONS: Org 25935 demonstrated no
      benefit over placebo in augmenting CBT for panic disorder. Study limitations and
      implications are discussed. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00725725.

PMID- 22394473
TI  - Nephrology: the flywheel of medicine during the last 60 years.

PMID- 22394472
TI  - Evolutionary aspects of human exercise--born to run purposefully.
AB  - This article is intended to raise awareness of the adaptive value of endurance
      exercise (particularly running) in the evolutionary history of humans, and the
      implications of the genetic disposition to exercise for the aging populations of
      modern technology-driven societies. The genome of Homo sapiens has evolved to
      support the svelte phenotype of an endurance runner, setting him/her apart from
      all other primates. The cellular and molecular mechanisms underlying the
      competitive advantages conferred by exercise capacity in youth can also provide a
      survival benefit beyond the reproductive period. These mechanisms include up
      regulation of genes encoding proteins involved in protecting cells against
      oxidative stress, disposing of damaged proteins and organelles, and enhancing
      bioenergetics. Particularly fascinating are the signaling mechanisms by which
      endurance running changes the structure and functional capabilities of the brain
      and, conversely, the mechanisms by which the brain integrates metabolic,
      cardiovascular and behavioral responses to exercise. As an emerging example, I
      highlight the roles of brain-derived neurotrophic factor (BDNF) as a mediator of
      the effects of exercise on the brain, and BDNF's critical role in regulating
      metabolic and cardiovascular responses to endurance running. A better
      understanding of such 'healthspan-extending' actions of endurance exercise may
      lead to new approaches for improving quality of life as we advance in the coming
      decades and centuries.

PMID- 22394474
TI  - Artificial organs 2011: a year in review.
AB  - In this Editor's Review, articles published in 2011 are organized by category and
      briefly summarized. As the official journal of The International Federation for
      Artificial Organs, The International Faculty for Artificial Organs, and the
      International Society for Rotary Blood Pumps, Artificial Organs continues in the
      original mission of its founders "to foster communications in the field of
      artificial organs on an international level."Artificial Organs continues to
      publish developments and clinical applications of artificial organ technologies
      in this broad and expanding field of organ replacement, recovery, and
      regeneration from all over the world. We take this time also to express our
      gratitude to our authors for offering their work to this journal. We offer our
      very special thanks to our reviewers who give so generously of time and expertise
      to review, critique, and especially provide meaningful suggestions to the
      author's work whether eventually accepted or rejected. Without these excellent
      and dedicated reviewers, the quality expected from such a journal would not be
      possible. We also express our special thanks to our Publisher, Wiley-Blackwell,
      for their expert attention and support in the production and marketing of
      Artificial Organs. In this Editor's Review, that historically has been widely
      well-received by our readership, we aim to provide a brief reflection of the
      currently available worldwide knowledge that is intended to advance and better
      human life while providing insight for continued application of technologies and
      methods of organ replacement, recovery, and regeneration. We look forward to
      recording further advances in the coming years.

PMID- 22394476
TI  - First-episode psychosis at the West Bologna Community Mental Health Centre:
      results of an 8-year prospective study.
AB  - BACKGROUND: Research mostly conducted in the UK and northern Europe has
      established that there are high rates of first-episode psychosis (FEP) in large
      cities and immigrant populations; moreover, psychosis has been found to be
      associated with cannabis use and early trauma. The present study aimed to
      evaluate the incidence rate of FEP and the distribution of several risk factors
      (e.g. age, ethnicity, substance abuse) in Bologna, Italy. METHOD: The Bologna FEP
      (BoFEP) study is an 8-year prospective study. All FEP patients, 18-64 years old,
      consecutively referred to the West Bologna Community Mental Health Centre (CMHC)
      from 2002 to 2009 were evaluated. Sociodemographic information, migration history
      and clinical data were collected through an ad-hoc schedule. Psychiatric
      diagnoses were recorded using the Schedule for Clinical Assessment of
      Neuropsychiatry (SCAN). RESULTS: The overall incidence rate (IR) in the BoFEP
      study was 16.4 per 100 000 person-years [95% confidence interval (CI) 13.9-18.9].
      The incidence was higher in young people, men and migrants (MI). CONCLUSIONS: The
      IR of FEP found by the Bologna study is lower than that found by other European
      studies. However, as in other studies, the incidence was higher in certain
      groups. This heterogeneity has implications for policy and mental health service
      development, and for understanding the aetiology of psychosis.

PMID- 22394477
TI  - Magnetic nanoparticle density mapping from the magnetically induced displacement
      data: a simulation study.
AB  - BACKGROUND: Magnetic nanoparticles are gaining great roles in biomedical
      applications as targeted drug delivery agents or targeted imaging contrast
      agents. In the magnetic nanoparticle applications, quantification of the
      nanoparticle density deposited in a specified region is of great importance for
      evaluating the delivery of the drugs or the contrast agents to the targeted
      tissues. We introduce a method for estimating the nanoparticle density from the
      displacement of tissues caused by the external magnetic field. METHODS: We can
      exert magnetic force to the magnetic nanoparticles residing in a living subject
      by applying magnetic gradient field to them. The nanoparticles under the external
      magnetic field then exert force to the nearby tissues causing displacement of the
      tissues. The displacement field induced by the nanoparticles under the external
      magnetic field is governed by the Navier's equation. We use an approximation
      method to get the inverse solution of the Navier's equation which represents the
      magnetic nanoparticle density map when the magnetic nanoparticles are
      mechanically coupled with the surrounding tissues. To produce the external
      magnetic field inside a living subject, we propose a coil configuration, the
      Helmholtz and Maxwell coil pair, that is capable of generating uniform magnetic
      gradient field. We have estimated the coil currents that can induce measurable
      displacement in soft tissues through finite element method (FEM) analysis.
      RESULTS: From the displacement data obtained from FEM analysis of a soft-tissue
      mimicking phantom, we have calculated nanoparticle density maps. We obtained the
      magnetic nanoparticle density maps by approximating the Navier's equation to the
      Laplacian of the displacement field. The calculated density maps match well to
      the original density maps, but with some halo artifacts around the high density
      area. To induce measurable displacement in the living tissues with the proposed
      coil configuration, we need to apply the coil currents as big as 104A.
      CONCLUSIONS: We can obtain magnetic nanoparticle maps from the magnetically
      induced displacement data by approximating the Navier's equation under the
      assumption of uniform-gradient of the external magnetic field. However,
      developing a coil driving system with the capacity of up to 104A should be a
      great technical challenge.

PMID- 22394478
TI  - Drug target validation of the trypanothione pathway enzymes through metabolic
      modelling.
AB  - A kinetic model of trypanothione [T(SH)(2)] metabolism in Trypanosoma cruzi was
      constructed based on enzyme kinetic parameters determined under near
      physiological conditions (including glutathione synthetase), and the enzyme
      activities, metabolite concentrations and fluxes determined in the parasite under
      control and oxidizing conditions. The pathway structure is characterized by a
      T(SH)(2) synthetic module of low flux and low catalytic capacity, and another
      more catalytically efficient T(SH)(2) -dependent antioxidant/regenerating module.
      The model allowed quantification of the contribution of each enzyme to the
      control of T(SH)(2) synthesis and concentration (flux control and concentration
      control coefficients, respectively). The main control of flux was exerted by
      gamma-glutamylcysteine synthetase (gammaECS) and trypanothione synthetase (TryS)
      (control coefficients of 0.58-0.7 and 0.49-0.58, respectively), followed by
      spermidine transport (0.24); negligible flux controls by trypantothione reductase
      (TryR) and the T(SH)(2)-dependent antioxidant machinery were determined. The
      concentration of reduced T(SH)(2) was controlled by TryR (0.98) and oxidative
      stress (-0.99); however, gammaECS and TryS also exerted control on the cellular
      level of T(SH(2)) when they were inhibited by more than 70%. The model predicted
      that in order to diminish the T(SH)(2) synthesis flux by 50%, it is necessary to
      inhibit gammaECS or TryS by 58 or 63%, respectively, or both by 50%, whereas more
      than 98% inhibition was required for TryR. Hence, simultaneous and moderate
      inhibition of gammaECS and TryS appears to be a promising multi-target
      therapeutic strategy. In contrast, use of highly potent and specific inhibitors
      for TryR and the antioxidant machinery is necessary to affect the antioxidant
      capabilities of the parasites.

PMID- 22394479
TI  - Long anterior lens zonules.

PMID- 22394480
TI  - Multiresidue analysis of 58 pesticides in bean products by disposable pipet
      extraction (DPX) cleanup and gas chromatography-mass spectrometry determination.
AB  - A method based on disposable pipet extraction (DPX) sample cleanup and gas
      chromatography with mass spectrometric detection by selected ion monitoring
      (GC/MS-SIM) was established for 58 targeted pesticide residues in soybean, mung
      bean, adzuki bean and black bean. Samples were extracted with acetonitrile and
      concentrated (nitrogen gas flow) prior to being aspirated into DPX tubes. Cleanup
      procedure was achieved in a simple DPX-Qg tube. Matrix-matched calibrations were
      analyzed, and the limits of quantification (LOQ) of this method ranged from 0.01
      mg kg(-1) to 0.1 mg kg(-1) for all target compounds. Coefficients of
      determination of the linear ranges were between 0.9919 and 0.9998. Recoveries of
      fortified level 0.02 mg kg(-1) on soybean, mung bean, adzuki bean and black bean
      were 70.2-109.6%, 69.1-119.0%, 69.1-119.8%, and 69.0-120.8%, respectively, for
      all studied pesticides. Moreover, pesticide risk assessment for all the detected
      residues in 178 market samples at Beijing market area was conducted. A maximum
      0.958% of ADI (acceptable daily intake) for NESDI (national estimated daily
      intake) and 55.1% of ARfD (acute reference dose) for NESTI (national estimated
      short-term intake) indicated low diet risk of these products.

PMID- 22394482
TI  - Using epidemiology and neurotoxicology to reduce risks to young workers.
AB  - Children around the world are working in hazardous or unsafe conditions and they
      are at risk to injury through manual labor and susceptible to poisoning due to
      chemical exposures in the work place. Because of their behavior and the
      developmental changes occurring throughout childhood and adolescence children are
      more vulnerable to injury. Often children work because of economic necessity,
      coming from families living in extreme poverty, with poor housing conditions,
      unsafe water supplies, poor sanitation, and inadequate food supplies making them
      even more vulnerable to poor developmental outcomes. This presents a multifaceted
      problem that can be challenging to address. Although many studies have examined
      occupational risks among adults very few studies have examined the impact of
      these risks on children. This paper reflects a summary of the talks from the
      symposium "Using Epidemiology and Neurotoxicology to Reduce Risks to Young
      Workers" presented at the 13th International Neurotoxicology Association Meeting
      and the 11th International Symposium on Neurobehavioral Methods and Effects in
      Occupational and Environmental Health in Xi'an China in June 2011.
      Epidemiological studies have demonstrated that children are exposed to various
      neurotoxicants, show increased symptoms and health problems and are working in
      hazardous conditions with minimal safety restrictions. Other studies have
      identified neurotoxicology effects in children from occupational exposures.
      Prevention methods have potential for reducing risks to young workers short of
      eliminating child labor and should be addressed to multiple stakeholders,
      parents, employers and children.

PMID- 22394481
TI  - Non-coding RNAs--novel targets in neurotoxicity.
AB  - Over the past ten years non-coding RNAs (ncRNAs) have emerged as pivotal players
      in fundamental physiological and cellular processes and have been increasingly
      implicated in cancer, immune disorders, and cardiovascular, neurodegenerative,
      and metabolic diseases. MicroRNAs (miRNAs) represent a class of ncRNA molecules
      that function as negative regulators of post-transcriptional gene expression.
      miRNAs are predicted to regulate 60% of all human protein-coding genes and as
      such, play key roles in cellular and developmental processes, human health, and
      disease. Relative to counterparts that lack bindings sites for miRNAs, genes
      encoding proteins that are post-transcriptionally regulated by miRNAs are twice
      as likely to be sensitive to environmental chemical exposure. Not surprisingly,
      miRNAs have been recognized as targets or effectors of nervous system,
      developmental, hepatic, and carcinogenic toxicants, and have been identified as
      putative regulators of phase I xenobiotic-metabolizing enzymes. In this review,
      we give an overview of the types of ncRNAs and highlight their roles in
      neurodevelopment, neurological disease, activity-dependent signaling, and drug
      metabolism. We then delve into specific examples that illustrate their importance
      as mediators, effectors, or adaptive agents of neurotoxicants or neuroactive
      pharmaceutical compounds. Finally, we identify a number of outstanding questions
      regarding ncRNAs and neurotoxicity.

PMID- 22394484
TI  - Parallel evolution of TCP and B-class genes in Commelinaceae flower bilateral
      symmetry.
AB  - BACKGROUND: Flower bilateral symmetry (zygomorphy) has evolved multiple times
      independently across angiosperms and is correlated with increased pollinator
      specialization and speciation rates. Functional and expression analyses in
      distantly related core eudicots and monocots implicate independent recruitment of
      class II TCP genes in the evolution of flower bilateral symmetry. Furthermore,
      available evidence suggests that monocot flower bilateral symmetry might also
      have evolved through changes in B-class homeotic MADS-box gene function. METHODS:
      In order to test the non-exclusive hypotheses that changes in TCP and B-class
      gene developmental function underlie flower symmetry evolution in the monocot
      family Commelinaceae, we compared expression patterns of teosinte branched1 (TB1)
      like, DEFICIENS (DEF)-like, and GLOBOSA (GLO)-like genes in morphologically
      distinct bilaterally symmetrical flowers of Commelina communis and Commelina
      dianthifolia, and radially symmetrical flowers of Tradescantia pallida. RESULTS:
      Expression data demonstrate that TB1-like genes are asymmetrically expressed in
      tepals of bilaterally symmetrical Commelina, but not radially symmetrical
      Tradescantia, flowers. Furthermore, DEF-like genes are expressed in showy inner
      tepals, staminodes and stamens of all three species, but not in the distinct
      outer tepal-like ventral inner tepals of C. communis. CONCLUSIONS: Together with
      other studies, these data suggest parallel recruitment of TB1-like genes in the
      independent evolution of flower bilateral symmetry at early stages of Commelina
      flower development, and the later stage homeotic transformation of C. communis
      inner tepals into outer tepals through the loss of DEF-like gene expression.

PMID- 22394483
TI  - Interrelationships of undernutrition and neurotoxicity: food for thought and
      research attention.
AB  - The neurotoxic actions of chemical agents on humans and animals are usually
      studied with little consideration of the subject's nutritional status. States of
      protein-calorie, vitamin and/or mineral undernutrition are associated with a
      range of neurodevelopmental, neurological and psychiatric disorders, commonly
      with involvement of both the central and the peripheral nervous system.
      Undernutrition can modify risk for certain chemical-induced neurologic diseases,
      and in some cases undernutrition may be a prerequisite for neurotoxicity to
      surface. In addition, neurologic disease associated with undernutrition or
      neurotoxicity may show similarities in clinical and neuropathological expression,
      especially in the peripheral nervous system. The combined effects of
      undernutrition and chemical neurotoxicity are most relevant to people with low
      incomes who experience chronic hunger, parasitism and infectious disease,
      monotonous diets of plants with neurotoxic potential (notably cassava),
      environmental pollution from rapid industrial development, chronic alcohol abuse,
      or prolonged treatment with certain therapeutic drugs. Undernutrition alone or in
      combination with chemical exposure is also important in high-income societies in
      the setting of drug and alcohol abuse, old age, food faddism, post-bariatric
      surgery, and drug treatment for certain medical conditions, including cancer and
      tuberculosis. The nutritional demands of pregnancy and lactation increase the
      risk of fetal and infant undernutrition and chemical interactions therewith.

PMID- 22394485
TI  - Early neural crest induction requires an initial inhibition of Wnt signals.
AB  - Neural crest (NC) induction is a long process that continues through gastrula and
      neurula stages. In order to reveal additional stages of NC induction we performed
      a series of explants where different known inducing tissues were taken along with
      the prospective NC. Interestingly the dorso-lateral marginal zone (DLMZ) is only
      able to promote the expression of a subset of neural plate border (NPB) makers
      without the presence of specific NC markers. We then analysed the temporal
      requirement for BMP and Wnt signals for the NPB genes Hairy2a and Dlx5, compared
      to the expression of neural plate (NP) and NC genes. Although the NP is sensitive
      to BMP levels at early gastrula stages, Hairy2a/Dlx5 expression is unaffected.
      Later, the NP becomes insensitive to BMP levels at late gastrulation when NC
      markers require an inhibition. The NP requires an inhibition of Wnt signals prior
      to gastrulation, but becomes insensitive during early gastrula stages when
      Hairy2a/Dlx5 requires an inhibition of Wnt signalling. An increase in Wnt
      signalling is then important for the switch from NPB to NC at late gastrula
      stages. In addition to revealing an additional distinct signalling event in NC
      induction, this work emphasizes the importance of integrating both timing and
      levels of signalling activity during the patterning of complex tissues such as
      the vertebrate ectoderm.

PMID- 22394486
TI  - Nemo phosphorylates Eyes absent and enhances output from the Eya-Sine oculis
      transcriptional complex during Drosophila retinal determination.
AB  - The retinal determination gene network comprises a collection of transcription
      factors that respond to multiple signaling inputs to direct Drosophila eye
      development. Previous genetic studies have shown that nemo (nmo), a gene encoding
      a proline-directed serine/threonine kinase, can promote retinal specification
      through interactions with the retinal determination gene network, although the
      molecular point of cross-talk was not defined. Here, we report that the Nemo
      kinase positively and directly regulates Eyes absent (Eya). Genetic assays show
      that Nmo catalytic activity enhances Eya-mediated ectopic eye formation and
      potentiates induction of the Eya-Sine oculis (So) transcriptional targets
      dachshund and lozenge. Biochemical analyses demonstrate that Nmo forms a complex
      with and phosphorylates Eya at two consensus mitogen-activated protein kinase
      (MAPK) phosphorylation sites. These same sites appear crucial for Nmo-mediated
      activation of Eya function in vivo. Thus, we propose that Nmo phosphorylation of
      Eya potentiates its transactivation function to enhance transcription of Eya-So
      target genes during eye specification and development.

PMID- 22394487
TI  - Cortical aPKC kinase activity distinguishes neural stem cells from progenitor
      cells by ensuring asymmetric segregation of Numb.
AB  - During asymmetric stem cell division, polarization of the cell cortex targets
      fate determinants unequally into the sibling daughters, leading to regeneration
      of a stem cell and production of a progenitor cell with restricted developmental
      potential. In mitotic neural stem cells (neuroblasts) in fly larval brains, the
      antagonistic interaction between the polarity proteins Lethal (2) giant larvae
      (Lgl) and atypical Protein Kinase C (aPKC) ensures self-renewal of a daughter
      neuroblast and generation of a progenitor cell by regulating asymmetric
      segregation of fate determinants. In the absence of lgl function, elevated
      cortical aPKC kinase activity perturbs unequal partitioning of the fate
      determinants including Numb and induces supernumerary neuroblasts in larval
      brains. However, whether increased aPKC function triggers formation of excess
      neuroblasts by inactivating Numb remains controversial. To investigate how
      increased cortical aPKC function induces formation of excess neuroblasts, we
      analyzed the fate of cells in neuroblast lineage clones in lgl mutant brains.
      Surprisingly, our analyses revealed that neuroblasts in lgl mutant brains undergo
      asymmetric division to produce progenitor cells, which then revert back into
      neuroblasts. In lgl mutant brains, Numb remained localized in the cortex of
      mitotic neuroblasts and failed to segregate exclusively into the progenitor cell
      following completion of asymmetric division. These results led us to propose that
      elevated aPKC function in the cortex of mitotic neuroblasts reduces the function
      of Numb in the future progenitor cells. We identified that the acyl-CoA binding
      domain containing 3 protein (ACBD3) binding region is essential for asymmetric
      segregation of Numb in mitotic neuroblasts and suppression of the supernumerary
      neuroblast phenotype induced by increased aPKC function. The ACBD3 binding region
      of Numb harbors two aPKC phosphorylation sites, serines 48 and 52. Surprisingly,
      while the phosphorylation status at these two sites directly impinged on
      asymmetric segregation of Numb in mitotic neuroblasts, both the phosphomimetic
      and non-phosphorylatable forms of Numb suppressed formation of excess neuroblasts
      triggered by increased cortical aPKC function. Thus, we propose that precise
      regulation of cortical aPKC kinase activity distinguishes the sibling cell
      identity in part by ensuring asymmetric partitioning of Numb into the future
      progenitor cell where Numb maintains restricted potential independently of
      regulation by aPKC.

PMID- 22394489
TI  - Use of iris recognition camera technology for the quantification of corneal
      opacification in mucopolysaccharidoses.
AB  - Mucopolysaccharidoses (MPS) can cause corneal opacification that is currently
      difficult to objectively quantify. With newer treatments for MPS comes an
      increased need for a more objective, valid and reliable index of disease severity
      for clinical and research use. Clinical evaluation by slit lamp is very
      subjective and techniques based on colour photography are difficult to
      standardise. In this article the authors present evidence for the utility of
      dedicated image analysis algorithms applied to images obtained by a highly
      sophisticated iris recognition camera that is small, manoeuvrable and adapted to
      achieve rapid, reliable and standardised objective imaging in a wide variety of
      patients while minimising artefactual interference in image quality.

PMID- 22394488
TI  - Diagnostic value of anti-mutated citrullinated vimentin in comparison to anti
      cyclic citrullinated peptide and anti-viral citrullinated peptide 2 antibodies in
      rheumatoid arthritis: an Italian multicentric study and review of the literature.
AB  - In the last years, the detection of antibodies (Abs) against citrullinated
      peptides (ACPA) has largely replaced rheumatoid factor (RF) as the most helpful
      biomarker in the diagnosis of rheumatoid arthritis (RA). Current assays detect
      ACPA reactivity with epitopes on various different citrullinated proteins. Among
      these, anti-cyclic citrullinated peptide (CCP) Abs have been widely demonstrated
      to be an important diagnostic and prognostic tool because of their high
      specificity. Recently, citrullinated vimentin, a protein highly released in
      synovial microenvironment, has been identified as potential autoantigen in the
      pathophysiology of RA and an enzyme-linked immunosorbent assay (ELISA) for the
      detection of Abs directed against a mutated citrullinated vimentin (anti-MCV) was
      developed. Several recent studies evaluating the characteristics of anti-MCV in
      comparison to anti-CCP Abs, have given conflicting results. Anti-MCV have been
      demonstrated to perform better than anti-CCP as predictor of radiographic damage.
      Conversely, its additional diagnostic and prognostic role in comparison to anti
      CCP in both early and established RA is controversial. Aim of this study was to
      evaluate the diagnostic performance of anti-MCV in RA and to compare it to anti
      CCP and the recently developed assay targeting viral citrullinated peptide 2
      (VCP2) in a large cohort of RA patients (n=285), healthy subjects and other
      disease controls (n=227). Anti-MCV resulted to have a sensitivity of 59% and a
      specificity of 92%. In comparison, anti-CCP and anti-VCP2 displayed a sensitivity
      of 77% and 61% and a specificity of 96% and 95%, respectively. Of interest, at
      the manufacturer recommended cutoff value of 20U/mL, a high percentage of healthy
      subjects as well as Epstein Barr (EBV) and hepatitis C (HCV) virus infected
      patients resulted anti-MCV positive. In our large cohort of RA patients, anti-MCV
      demonstrated lower sensitivity than anti-CCP and VCP2 test, thus not allowing to
      confirm previously published data. Moreover, the high rate of detection in
      infectious diseases limits its diagnostic value in undifferentiated arthritis.

PMID- 22394490
TI  - Isolation of dimorphic chloroplasts from the single-cell C4 species Bienertia
      sinuspersici.
AB  - Three terrestrial plants are known to perform C4 photosynthesis without the dual
      cell system by partitioning two distinct types of chloroplasts in separate
      cytoplasmic compartments. We report herein a protocol for isolating the dimorphic
      chloroplasts from Bienertia sinuspersici. Hypo-osmotically lysed protoplasts
      under our defined conditions released intact compartments containing the central
      chloroplasts and intact vacuoles with adhering peripheral chloroplasts. Following
      Percoll step gradient purification both chloroplast preparations demonstrated
      high homogeneities as evaluated from the relative abundance of respective protein
      markers. This protocol will open novel research directions toward understanding
      the mechanism of single-cell C4 photosynthesis.

PMID- 22394491
TI  - NGO-provided free HIV treatment and services in Burkina Faso: scarcity,
      therapeutic rationality and unfair process.
AB  - Until 2010, Burkina Faso was an exception to the international trend of
      abolishing user fees for antiretroviral treatment (ART). Patients were still
      expected to pay 1,500F CFA (2 Euros) per month for ART. Nevertheless, many non
      governmental organizations (NGOs) exempted patients from payment. The objective
      of this study was to investigate how NGOs selected the beneficiaries of payment
      exemptions for government-provided ART and rationed out complementary medical and
      psychosocial services. For this qualitative study, we conducted 13 individual
      interviews and three focus group discussions (n = 13 persons) with program staff
      in nine NGOs (4,000 patients), two NGO coordinating structures and one national
      program. These encounters were recorded and transcribed, and their content was
      thematically analyzed. The results were presented to the NGOs for feedback.
      Results indicate that there are no concrete guidelines for identifying patients
      warranting payment exemptions. Formerly, ART was scarce in Burkina Faso and the
      primary criterion for treatment selection was clinical. Our results suggest that
      this scarcity, mediated by an approach we call sociotherapeutic rationality (i.e.
      maximization of clinical success), may have led to inequities in the provision of
      free ART. This approach may be detrimental to assuring equity since the most
      impoverished lack resources to pay for services that maximize clinical success
      (e.g. viral load) that would increase their chances of being selected for
      treatment. However, once selected into treatment, attempts were made to ration
      out complementary services more equitably.This study demonstrates the risks
      entailed by medication scarcity, which presents NGOs and health professionals
      with impossible choices that run counter to the philosophy of equity in access to
      treatment. Amid growing concerns of an international funding retreat for ART, it
      is important to learn from the past in order to better manage the potentially
      inequitable consequences of ART scarcity.

PMID- 22394493
TI  - Cognitive behavioural group therapy for social phobia: evidence of
      transportability to community clinics.
AB  - Cognitive Behavioural Group Therapy (CBGT) for social phobia has been shown to be
      efficacious within research units and effective within a variety of real world
      clinical settings. However, most effectiveness studies of CBGT for social phobia
      have (a) used protocols without demonstrated efficacy, (b) not included direct
      comparison groups, and/or (c) contained features of efficacy trials. This study
      addressed these limitations by using a benchmarking strategy to compare outcomes
      from the same CBGT protocol used in both a research unit and a community clinic.
      Research (N = 71) and community (N = 94) patients completed the same 12-session
      protocol, which resulted in significant reductions in social anxiety and life
      interference at post-treatment. Compared to research unit patients, community
      patients had more severe symptoms and life interference at pre-treatment, and
      were more likely to be male, use medication, have comorbid disorders, and have
      lower educational attainment. Importantly, degree of improvement on social
      anxiety symptoms and life interference did not differ across the treatment
      settings for either completer or intention-to-treat analyses. There was some
      evidence that being younger, single, and having a depression diagnosis were
      associated with dropout. Pre-treatment symptoms and number of diagnoses predicted
      post-treatment symptoms. Consistent with previous uncontrolled trials, it is
      concluded that CBGT is effective within community mental health clinics.

PMID- 22394492
TI  - Predicting and improving the membrane permeability of peptidic small molecules.
AB  - We evaluate experimentally and computationally the membrane permeability of
      matched sets of peptidic small molecules bearing natural or bioisosteric
      unnatural amino acids. We find that the intentional introduction of hydrogen bond
      acceptor-donor pairs in such molecules can improve membrane permeability while
      retaining or improving other favorable drug-like properties. We employ an all
      atom force field based method to calculate changes in free energy associated with
      the transfer of the peptidic molecules from water to membrane. This computational
      method correctly predicts rank order experimental permeability trends within
      congeneric series and is much more predictive than calculations (e.g., clogP)
      that do not consider three-dimensional conformation.

PMID- 22394494
TI  - Translating research into practice in nursing homes: can we close the gap?
AB  - PURPOSE: A gap between research and practice in many nursing home (NH) care areas
      persists despite efforts by researchers, policy makers, advocacy groups, and NHs
      themselves to close it. The reasons are many, but two factors that have received
      scant attention are the dissemination process itself and the work of the
      disseminators or change agents. This review article examines these two elements
      through the conceptual lens of Roger's innovation dissemination model. DESIGN AND
      METHODS: The application of general principles of innovation dissemination
      suggests that NHs are characteristically slow to innovate and thus may need more
      time as well as more contact with outside change agents to adopt improved
      practices. RESULTS: A review of the translation strategies used by NH change
      agents to promote adoption of evidence-based practice in NHs suggests that their
      strategies inconsistently reflect lessons learned from the broader dissemination
      literature. IMPLICATIONS: NH-related research, policy, and practice
      recommendations for improving dissemination strategies are presented. If we can
      make better use of the resources currently devoted to disseminating best
      practices to NHs, we may be able to speed NHs' adoption of these practices.

PMID- 22394495
TI  - Geriatric education in the health professions: are we making progress?
AB  - PURPOSE: Relative to the overall population, older adults consume a
      disproportionally large percentage of health care resources. Despite advocacy and
      efforts initiated more than 30 years ago, the number of providers with
      specialized training in geriatrics is still not commensurate with the growing
      population of older adults. This contribution provides a contemporary update on
      the status of geriatric education and explores how geriatric coverage is valued,
      how geriatric competence is defined, and how students are evaluated for geriatric
      competencies. DESIGN AND METHODS: Semi-structured interviews were conducted with
      curriculum representatives from 7 health profession disciplines in a case study
      of one academic medical center. FINDINGS: Geriatric training varies across health
      professions' disciplines. Although participants recognized the unique needs of
      older patients and valued geriatric coverage, they identified shortage of time in
      packed curricula, lack of geriatrics-trained educators, absence of financial
      incentive, and low student demand (resulting from limited exposure to older
      adults and gerontological stereotyping) as barriers to improving geriatric
      training. IMPLICATIONS: Progress in including geriatric training within curricula
      across the health professions continues to lag behind need as a result of the
      continuing presence of barriers identified several decades ago. There remains an
      urgent need for institutional commitment to enhance geriatric education as a
      component of health professions curricula.

PMID- 22394496
TI  - Severe sustained cholestatic hepatitis following temozolomide in a patient with
      glioblastoma multiforme: case study and review of data from the FDA adverse event
      reporting system.
AB  - Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in
      adults. Its established first-line adjuvant treatment is radiotherapy in
      combination with temozolomide (TZM). Hematotoxicity is listed as a frequent
      adverse drug reaction in the US prescribing information and hepatotoxicity has
      been reported infrequently in the postmarketing period. We here present the case
      of a patient diagnosed with GBM who developed severe sustained cholestatic
      hepatitis following treatment with TZM. The cholestasis was not reversible after
      withdrawal of TZM during 6 months before the patient's death. Another 2 published
      case reports of sustained cholestasis following TZM treatment were identified;
      however, the sustained nature of cholestasis was not emphasized in these reports.
      Sixteen cases of cholestatic hepatitis/cholestasis associated with TZM were
      identified in the FDA spontaneous reporting system between 2007 and 2010.
      Information on the course of the cholestasis in these cases could not be
      retrieved. In the literature there are other published reports of hepatotoxicity
      associated with TZM that have reported reversibility upon withdrawal of the drug.
      Thus, TZM appears to cause different types of hepatotoxicity. Particular
      attention should be paid to sustained cholestasis as a very serious type of TZM
      associated liver toxicity.

PMID- 22394497
TI  - Expression of podoplanin in human astrocytic brain tumors is controlled by the
      PI3K-AKT-AP-1 signaling pathway and promoter methylation.
AB  - Recently, we found strong overexpression of the mucin-type glycoprotein
      podoplanin (PDPN) in human astrocytic brain tumors, specifically in primary
      glioblastoma multiforme (GB). In the current study, we show an inverse
      correlation between PDPN expression and PTEN levels in primary human GB and
      glioma cell lines, and we report elevated PDPN protein levels in the
      subventricular zone of brain tissue sections of PTEN-deficient mice. In human
      glioma cells lacking functional PTEN, reintroduction of wild-type PTEN,
      inhibition of the PTEN downstream target protein kinase B/AKT, or interference
      with transcription factor AP-1 function resulted in efficient downregulation of
      PDPN expression. In addition, we observed hypoxia-dependent PDPN transcriptional
      control and demonstrated that PDPN expression is subject to negative
      transcriptional regulation by promoter methylation in human GB and in glioma cell
      lines. Treatment of PTEN-negative glioma cells with demethylating agents induced
      expression of PDPN. Together, our findings show that increased PDPN expression in
      human GB is caused by loss of PTEN function and activation of the PI3K-AKT-AP-1
      signaling pathway, accompanied by epigenetic regulation of PDPN promoter
      activity. Silencing of PDPN expression leads to reduced proliferation and
      migration of glioma cells, suggesting a functional role of PDPN in glioma
      progression and malignancy. Thus, specific targeting of PDPN expression and/or
      function could be a promising strategy for the treatment of patients with primary
      GB.

PMID- 22394502
TI  - Evidence for regulated monoacylglycerol acyltransferase expression and activity
      in human liver.
AB  - Intrahepatic lipid accumulation is extremely common in obese subjects and is
      associated with the development of insulin resistance and diabetes. Hepatic
      diacylglycerol and triacylglycerol synthesis predominantly occurs through
      acylation of glycerol-3-phosphate. However, an alternative pathway for
      synthesizing diacylglycerol from monoacylglycerol acyltransferases (MGAT) could
      also contribute to hepatic glyceride pools. MGAT activity and the expression of
      the three genes encoding MGAT enzymes (MOGAT1, MOGAT2, and MOGAT3) were
      determined in liver biopsies from obese human subjects before and after gastric
      bypass surgery. MOGAT expression was also assessed in liver of subjects with
      nonalcoholic fatty liver disease (NAFLD) or control livers. All MOGAT genes were
      expressed in liver, and hepatic MGAT activity was readily detectable in liver
      lysates. The hepatic expression of MOGAT3 was highly correlated with MGAT
      activity, whereas MOGAT1 and MOGAT2 expression was not, and knockdown of MOGAT3
      expression attenuated MGAT activity in a liver-derived cell line. Marked weight
      loss following gastric bypass surgery was associated with a significant reduction
      in MOGAT2 and MOGAT3 expression, which were also overexpressed in NAFLD subjects.
      These data suggest that the MGAT pathway is active and dynamically regulated in
      human liver and could be an important target for pharmacologic intervention for
      the treatment of obesity-related insulin resistance and NAFLD.

PMID- 22394503
TI  - Endotoxin increase after fat overload is related to postprandial
      hypertriglyceridemia in morbidly obese patients.
AB  - The low-grade inflammation observed in obesity has been associated with a high
      fat diet, though this relation is not fully understood. Bacterial endotoxin,
      produced by gut microbiota, may be the linking factor. However, this has not been
      confirmed in obese patients. To study the relationship between a high-fat diet
      and bacterial endotoxin, we analyzed postprandial endotoxemia in morbidly obese
      patients after a fat overload. The endotoxin levels were determined in serum and
      the chylomicron fraction at baseline and 3 h after a fat overload in 40 morbidly
      obese patients and their levels related with the degree of insulin resistance and
      postprandial hypertriglyceridemia. The morbidly obese patients with the highest
      postprandial hypertriglyceridemia showed a significant increase in
      lipopolysaccharide (LPS) levels in serum and the chylomicron fraction after the
      fat overload. Postprandial chylomicron LPS levels correlated positively with the
      difference between postprandial triglycerides and baseline triglycerides. There
      were no significant correlations between C-reactive protein (CRP) and LPS levels.
      The main variables contributing to serum LPS levels after fat overload were
      baseline and postprandial triglyceride levels but not glucose or insulin
      resistance. Additionally, superoxide dismutase activity decreased significantly
      after the fat overload. Postprandial LPS increase after a fat overload is related
      to postprandial hypertriglyceridemia but not to degree of insulin resistance in
      morbidly obese patients.

PMID- 22394505
TI  - Luteolin inhibits pyrogallol-induced apoptosis through the extracellular signal
      regulated kinase signaling pathway.
AB  - Luteolin is an antioxidative, antitumor and anti-inflammatory flavone. It has
      been shown to reduce endothelial dysfunction, but the mechanism is not clear. We
      set out to explore the effects of luteolin on apoptosis and its mechanism of
      action in endothelial cells. The effect of luteolin on pyrogallol-induced
      superoxide stress and the subsequent apoptosis was studied in the mouse heart
      capillary endothelial cell line H5V and human umbilical vein endothelial cells,
      by the use of flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide, Hoechst staining, and western blot. Pyrogallol (0-400 MUm)
      dose-dependently induced reactive oxygen species production, cytotoxicity, an
      annexin V-fluorescein isothiocyanate increase, mitochondrial transmembrane
      depolarization and DNA condensation in both H5V and human umbilical vein
      endothelial cells; these actions were reversed by luteolin (0.78-50 MUm) in a
      concentration-dependent manner. Luteolin suppressed the poly (ADP-ribose)
      polymerase activation, caspase-8 cleavage and p38 mitogen-activated protein
      kinase activation triggered by pyrogallol, and stimulated the extracellular
      signal-regulated kinase signaling pathway to counteract the pyrogallol-induced
      apoptotic signals. Luteolin is an effective agent for the protection of
      endothelial cells from superoxide stress-induced apoptosis via the extracellular
      signal-regulated kinase signaling pathway.

PMID- 22394504
TI  - Identification and characterization of microRNAs in Phaseolus vulgaris by high
      throughput sequencing.
AB  - BACKGROUND: MicroRNAs (miRNAs) are endogenously encoded small RNAs that post
      transcriptionally regulate gene expression. MiRNAs play essential roles in almost
      all plant biological processes. Currently, few miRNAs have been identified in the
      model food legume Phaseolus vulgaris (common bean). Recent advances in next
      generation sequencing technologies have allowed the identification of conserved
      and novel miRNAs in many plant species. Here, we used Illumina's sequencing by
      synthesis (SBS) technology to identify and characterize the miRNA population of
      Phaseolus vulgaris. RESULTS: Small RNA libraries were generated from roots,
      flowers, leaves, and seedlings of P. vulgaris. Based on similarity to previously
      reported plant miRNAs,114 miRNAs belonging to 33 conserved miRNA families were
      identified. Stem-loop precursors and target gene sequences for several conserved
      common bean miRNAs were determined from publicly available databases. Less
      conserved miRNA families and species-specific common bean miRNA isoforms were
      also characterized. Moreover, novel miRNAs based on the small RNAs were found and
      their potential precursors were predicted. In addition, new target candidates for
      novel and conserved miRNAs were proposed. Finally, we studied organ-specific
      miRNA family expression levels through miRNA read frequencies. CONCLUSIONS: This
      work represents the first massive-scale RNA sequencing study performed in
      Phaseolus vulgaris to identify and characterize its miRNA population. It
      significantly increases the number of miRNAs, precursors, and targets identified
      in this agronomically important species. The miRNA expression analysis provides a
      foundation for understanding common bean miRNA organ-specific expression
      patterns. The present study offers an expanded picture of P. vulgaris miRNAs in
      relation to those of other legumes.

PMID- 22394506
TI  - Regulation of cell proliferation and cell density by the inorganic phosphate
      transporter PiT1.
AB  - ABSTACT: BACKGROUND: The inorganic phosphate (Pi) transporter, PiT1 (SLC20A1), is
      ubiquitously expressed in mammalian cells. It has previously been shown that down
      regulation of PiT1 severely impaired the proliferation of two transformed human
      cells lines, HepG2 and HeLa, and the tumorigenicity of HeLa cells in nude mice.
      Moreover, PiT1 knock-out mice do not survive past E12.5 and from E10.5, the
      embryos were found to be growth-retarded and showed reduced proliferation of
      liver cells. Isolated mouse embryonic fibroblasts with knocked out as well as
      reduced PiT1 expression levels also exhibited impaired proliferation. Together
      these results suggest that a certain level of PiT1 is important for
      proliferation. We have here investigated the role of PiT1 in regulation of cell
      proliferation using two strictly density-inhibited cells lines, the murine MC3T3
      E1 and NIH3T3 cells. RESULTS: We found that knock-down of PiT1 in MC3T3-E1 cells
      led to impaired proliferation supporting that at least a certain level of PiT1 is
      important for wildtype level of proliferation. We, however, also observed that
      MC3T3-E1 and NIH3T3 cells themselves regulate their endogenous PiT1 mRNA levels
      with lower levels in general correlating with decreased proliferation/increased
      cell density. Moreover, over-expression of human PiT1 led to increased
      proliferation of both MC3T3-E1 and NIH3T3 cultures and resulted in higher cell
      densities in cultures of these two strictly density-inhibited cell lines. In
      addition, when we transformed NIH3T3 cells by cultivation in fetal bovine serum,
      cells over-expressing human PiT1 formed more colonies in soft agar than control
      cells. CONCLUSIONS: We conclude that not only is a certain level of PiT1
      necessary for normal cell division as suggested by previously published studies,
      rather the cellular PiT1 level is involved in regulating cell proliferation and
      cell density and an increased PiT1 expression can indeed make NIH3T3 cells more
      sensitive to transformation. We have thus provided the first evidence for that
      expression of the type III Pi transporter, PiT1, above the endogenous level can
      drive cell proliferation and overrule cell density constraints, and the results
      bridge previous observations showing that a certain PiT1 level is important for
      regulating normal embryonic growth/development and for tumorigenicity of HeLa
      cells.

PMID- 22394507
TI  - Quercetin abrogates IL-6/STAT3 signaling and inhibits glioblastoma cell line
      growth and migration.
AB  - Evidence has suggested that STAT3 functions as an oncogene in gliomagenesis. As a
      consequence, changes in the inflammatory microenvironment are thought to promote
      tumor development. Regardless of its origin, cancer-related inflammation has many
      tumor-promoting effects, such as the promotion of cell cycle progression, cell
      proliferation, cell migration and cell survival. Given that IL-6, a major cancer
      related inflammatory cytokine, regulates STAT3 activation and is upregulated in
      glioblastoma, we sought to investigate the inhibitory effects of the
      chemopreventive flavonoid quercetin on glioblastoma cell proliferation and
      migration triggered by IL-6, and to determine the underlying mechanisms of
      action. In this study, we show that quercetin is a potent inhibitor of the IL-6
      induced STAT3 signaling pathway in T98G and U87 glioblastoma cells. Exposure to
      quercetin resulted in the reduction of GP130, JAK1 and STAT3 activation by IL-6,
      as well as a marked decrease of the proliferative and migratory properties of
      glioblastoma cells induced by IL-6. Interestingly, quercetin also modulated the
      expression of two target genes regulated by STAT3, i.e. cyclin D1 and matrix
      metalloproteinase-2 (MMP-2). Moreover, quercetin reduced the recruitment of STAT3
      at the cyclin D1 promoter and inhibited Rb phosphorylation in the presence of IL
      6. Overall, these results provide new insight into the role of quercetin as a
      blocker of the STAT3 activation pathway stimulated by IL-6, with a potential role
      in the prevention and treatment of glioblastoma.

PMID- 22394508
TI  - Chromosomal, metabolic, environmental, and hormonal origins of aneuploidy in
      mammalian oocytes.
AB  - Aneuploidy is a leading cause of early embryo loss, miscarriage and birth defects
      in humans. It is predominantly brought about by the mis-segregation of homologous
      chromosomes (bivalents) in the first meiotic division (MI) of the oocyte, with
      advanced maternal age being a risk factor. Although its etiology is likely to be
      multifactorial the predominating factors remain amenable for study in models such
      as mice. Homologous chromosome separation in MI is achieved by the mono
      orientation of functionally paired sister kinetochores but despite this unique
      division the Spindle Assembly Checkpoint (SAC), which prevents sister chromatid
      mis-segregation in mitosis, is functional in mouse oocytes. However, it remains
      to be fully established what types of error the SAC respond to, for example the
      presence of univalents, and how sensitive it is to attachment or tension defects
      in bivalent alignment. Such errors may increase with advanced maternal age as
      chromosomes lose their cohesive ties and the oocyte has less capacity to service
      the metabolic needs associated with meiotic division. Environmental insults and
      hormonal changes could also affect the fidelity of this process. Here we review
      how all these factors converge on the meiotic spindle during MI to cause mis
      segregation errors.

PMID- 22394509
TI  - The mammalian synaptonemal complex: protein components, assembly and role in
      meiotic recombination.
AB  - The synaptonemal complex (SC) is a proteinaceous structure of chromosome
      bivalents whose assembly is indispensable for the successful progression of the
      first meiotic division of sexually reproducing organisms. In this mini-review we
      will focus on recent progress dealing with the composition and assembly of the
      mammalian SC. These advances mainly resulted from the systematic use of knockout
      mice for all known mammalian SC proteins as well as from protein polymerization
      studies performed in heterologous systems.

PMID- 22394510
TI  - Chromatin organization - the 30 nm fiber.
AB  - Despite over 30 years of work, the fundamental structure of eukaryotic chromatin
      remains controversial. Here, we review the roots of this controversy in
      disparities between results derived from studies of chromatin in nuclei,
      chromatin isolated from nuclei, and chromatin reconstituted from defined
      components. Thanks to recent advances in imaging, modeling, and other approaches,
      it is now possible to recognize some unifying principles driving chromatin
      architecture at the level of the ubiquitous '30 nm' chromatin fiber. These
      suggest that fiber architecture involves both zigzag and bent linker motifs, and
      that such heteromorphic structures facilitate the observed high packing ratios.
      Interactions between neighboring fibers in highly compact chromatin lead to
      extensive interdigitation of nucleosomes and the inability to resolve individual
      fibers in compact chromatin in situ.

PMID- 22394511
TI  - The development of a population-level clinical screening tool for self-harm
      repetition and suicide: the ReACT Self-Harm Rule.
AB  - BACKGROUND: Self-harm is a common reason for Emergency Department (ED)
      attendance. We aimed to develop a clinical tool to help identify patients at
      higher risk of repeat self-harm, or suicide, within 6 months of an ED self-harm
      presentation. METHOD: The tool, the ReACT Self-Harm Rule, was derived using
      multicentre data from a prospective cohort study. Binary recursive partitioning
      was applied to data from two centres, and data from a separate centre were used
      to test the tool. There were 29 571 self-harm presentations to five hospital EDs
      between January 2003 and June 2007, involving 18 680 adults aged ?16 years. We
      estimated sensitivity, specificity and positive and negative predictive values to
      measure the performance of the tool. RESULTS: A self-harm presentation was
      classified as higher risk if at least one of the following factors was present:
      recent self-harm (in the past year), living alone or homelessness, cutting as a
      method of harm and treatment for a current psychiatric disorder. The rule
      performed with 95% sensitivity [95% confidence interval (CI) 94-95] and 21%
      specificity (95% CI 21-22), and had a positive predictive value of 30% (95% CI 30
      31) and a negative predictive value of 91% (95% CI 90-92) in the derivation
      centres; it identified 83/92 of all subsequent suicides. CONCLUSIONS: The ReACT
      Self-Harm Rule might be used as a screening tool to inform the process of
      assessing self-harm presentations to ED. The four risk factors could also be used
      as an adjunct to in-depth psychosocial assessment to help guide risk formulation.
      The use of multicentre data helped to maximize the generalizability of the tool,
      but we need to further verify its external validity in other localities.

PMID- 22394512
TI  - A novel whole-cell lysate kinase assay identifies substrates of the p38 MAPK in
      differentiating myoblasts.
AB  - BACKGROUND: The p38alpha mitogen-activated protein kinase (MAPK) is a critical
      mediator of myoblast differentiation, and does so in part through the
      phosphorylation and regulation of several transcription factors and chromatin
      remodelling proteins. However, whether p38alpha is involved in processes other
      than gene regulation during myogenesis is currently unknown, and why other p38
      isoforms cannot compensate for its loss is unclear. METHODS: To further
      characterise the involvement of p38alpha during myoblast differentiation, we
      developed and applied a simple technique for identifying relevant in vivo kinase
      substrates and their phosphorylation sites. In addition to identifying substrates
      for one kinase, the technique can be used in vitro to compare multiple kinases in
      the same experiment, and we made use of this to study the substrate specificities
      of the p38alpha and beta isoforms. RESULTS: Applying the technique to p38alpha
      resulted in the identification of seven in vivo phosphorylation sites on six
      proteins, four of which are cytoplasmic, in lysate derived from differentiating
      myoblasts. An in vitro comparison with p38beta revealed that substrate
      specificity does not discriminate these two isoforms, but rather that their
      distinguishing characteristic appears to be cellular localisation. CONCLUSION:
      Our results suggest p38alpha has a novel cytoplasmic role during myogenesis and
      that its unique cellular localisation may be why p38beta and other isoforms
      cannot compensate for its absence. The substrate-finding approach presented here
      also provides a necessary tool for studying the hundreds of protein kinases that
      exist and for uncovering the deeper mechanisms of phosphorylation-dependent cell
      signalling.

PMID- 22394513
TI  - Peptide truncation leads to a twist and an unusual increase in affinity for
      casitas B-lineage lymphoma tyrosine kinase binding domain.
AB  - We describe truncation and SAR studies to identify a pentapeptide that binds Cbl
      tyrosine kinase binding domain with a higher affinity than the parental peptide.
      The pentapeptide has an alternative binding mode that allows occupancy of a
      previously uncharacterized groove. A peptide library was used to map the binding
      site and define the interface landscape. Our results suggest that the
      pentapeptide is an ideal starting point for the development of inhibitors against
      Cbl driven diseases.

PMID- 22394514
TI  - Effects of hypothyroidism on the respiratory system and control of breathing:
      Human studies and animal models.
AB  - Hypothyroidism, subclinical hypothyroidism and euthyroid sick syndrome, are
      prevalent disorders that affect all body systems including the respiratory system
      and control of breathing. The purpose of this review article is to discuss the
      regulation of thyroid hormone production and their function at the cellular
      level; the many causes of hypothyroidism; the effects of hypothyroidism on the
      respiratory system and on control of ventilation in hypothyroid patients; the
      variety of ways animal models of hypothyroidism are induced; and how in animal
      models hypothyroidism affects the respiratory system and control of breathing
      including neurotransmitters that influence breathing. Finally, this review will
      present controversies that exist in the field and thus encourage new research
      directions. Because of the high prevalence of hypothyroidism and subclinical
      forms of hypothyroidism and their influence on ventilation and the respiratory
      system, understanding underlying molecular mechanisms is necessary to ascertain
      how and sometimes why not thyroid replacement may normalize function.

PMID- 22394515
TI  - Development and validation of a high-performance liquid chromatography method for
      the determination of diacetyl in beer using 4-nitro-o-phenylenediamine as the
      derivatization reagent.
AB  - Diacetyl is a natural byproduct of fermentation and known to be an important
      flavor compound in many food products. Because of the potential undesirable
      effects of diacetyl on health safety and beer flavor, determination of its
      concentration in beer samples is essential and its analytical methods have
      attracted close attention recently. The aim of the present work is to develop and
      validate a novel high-performance liquid chromatography method for the
      quantification of diacetyl in beer based on the derivatization reaction of
      diacetyl with 4-nitro-o-phenylenediamine (NPDA). After the derivatization with
      NPDA in pH 3.0 at 45  degrees C for 20 min, diacetyl was separated on a kromasil
      C(18) column at room temperature in the form of the resulting 6-nitro-2,3
      dimethylquinoxaline and detected by the ultraviolet detector at 257 nm. The
      results showed that the correlation coefficient for the method was 0.9992 in the
      range of 0.0050-10.0 mg L(-1) and the limit of detection was 0.0008 mg L(-1) at a
      signal-to-noise ratio of 3. The applicability of the proposed method was
      evaluated in the analysis of beer samples with the recovery range of 94.0-99.0%
      and relative standard deviation range of 1.20-3.10%. The concentration levels of
      diacetyl detected in beer samples from 12 brands ranged from 0.034 to 0.110 mg L(
      1). The proposed method showed efficient chromatographic separation, excellent
      linearity, and good repeatability that can be applied to quantification of
      diacetyl in beer samples.

PMID- 22394516
TI  - A cell-based phenotypic assay to identify cardioprotective agents.
AB  - RATIONALE: Tissue ischemia/reperfusion (IR) injury underlies several leading
      causes of death such as heart-attack and stroke. The lack of clinical therapies
      for IR injury may be partly due to the difficulty of adapting IR injury models to
      high-throughput screening (HTS). OBJECTIVE: To develop a model of IR injury that
      is both physiologically relevant and amenable to HTS. METHODS AND RESULTS: A
      microplate-based respirometry apparatus was used. Controlling gas flow in the
      plate head space, coupled with the instrument's mechanical systems, yielded a 24
      well model of IR injury in which H9c2 cardiomyocytes were transiently trapped in
      a small volume, rendering them ischemic. After initial validation with known
      protective molecules, the model was used to screen a 2000-molecule library, with
      post-IR cell death as an end point. Po2 and pH monitoring in each well also
      afforded metabolic data. Ten protective, detrimental, and inert molecules from
      the screen were subsequently tested in a Langendorff-perfused heart model of IR
      injury, revealing strong correlations between the screening end point and both
      recovery of cardiac function (negative, r2=0.66) and infarct size (positive,
      r2=0.62). Relationships between the effects of added molecules on cellular
      bioenergetics and protection against IR injury were also studied. CONCLUSIONS:
      This novel cell-based assay can predict either protective or detrimental effects
      on IR injury in the intact heart. Its application may help identify therapeutic
      or harmful molecules.

PMID- 22394517
TI  - Islet1 derivatives in the heart are of both neural crest and second heart field
      origin.
AB  - RATIONALE: Islet1 (Isl1) has been proposed as a marker of cardiac progenitor
      cells derived from the second heart field and is utilized to identify and purify
      cardiac progenitors from murine and human specimens for ex vivo expansion. The
      use of Isl1 as a specific second heart field marker is dependent on its exclusion
      from other cardiac lineages such as neural crest. OBJECTIVE: Determine whether
      Isl1 is expressed by cardiac neural crest. METHODS AND RESULTS: We used an
      intersectional fate-mapping system using the RC::FrePe allele, which reports dual
      Flpe and Cre recombination. Combining Isl1(Cre/+), a SHF driver, and Wnt1::Flpe,
      a neural crest driver, with Rc::FrePe reveals that some Isl1 derivatives in the
      cardiac outflow tract derive from Wnt1-expressing neural crest progenitors. In
      contrast, no overlap was observed between Wnt1-derived neural crest and an
      alternative second heart field driver, Mef2c-AHF-Cre. CONCLUSIONS: Isl1 is not
      restricted to second heart field progenitors in the developing heart but also
      labels cardiac neural crest. The intersection of Isl1 and Wnt1 lineages within
      the heart provides a caveat to using Isl1 as an exclusive second heart field
      cardiac progenitor marker and suggests that some Isl1-expressing progenitor cells
      derived from embryos, embryonic stem cultures, or induced pluripotent stem
      cultures may be of neural crest lineage.

PMID- 22394518
TI  - Explaining calcium-dependent gating of anoctamin-1 chloride channels requires a
      revised topology.
AB  - RATIONALE: Ca2+ -activated Cl channels play pivotal roles in the cardiovascular
      system. They regulate vascular smooth muscle tone and participate in cardiac
      action potential repolarization in some species. Ca2+ -activated Cl channels were
      recently discovered to be encoded by members of the anoctamin (Ano, also called
      Tmem16) superfamily, but the mechanisms of Ano1 gating by Ca2+ remain enigmatic.
      OBJECTIVE: The objective was to identify regions of Ano1 involved in channel
      gating by Ca2+. METHODS AND RESULTS: The Ca2+ sensitivity of Ano1 was estimated
      from rates of current activation, and deactivation in excised patches rapidly
      switched between zero and high Ca2+ on the cytoplasmic side. Mutation of
      glutamates E702 and E705 dramatically altered Ca2+ sensitivity. E702 and E705 are
      predicted to be in an extracellular loop, but antigenic epitopes introduced into
      this loop are not accessible to extracellular antibodies, suggesting this loop is
      intracellular. Cytoplasmically applied membrane-impermeant sulfhydryl reagents
      alter the Ca2+ sensitivity of Ano1 E702C and E705C as expected if E702 and E705
      are intracellular. Substituted cysteine accessibility mutagenesis of the putative
      re-entrant loop suggests that E702 and E705 are located adjacent to the Cl
      conduction pathway. CONCLUSIONS: We propose an alternative model of Ano1 topology
      based on mutagenesis, epitope accessibility, and cysteine-scanning accessibility.
      These data contradict the popular re-entrant loop model by showing that the
      putative fourth extracellular loop (ECL 4) is intracellular and may contain a
      Ca2+ binding site. These studies provide new perspectives on regulation of Ano1
      by Ca2+.

PMID- 22394519
TI  - Lack of neutrophil-derived CRAMP reduces atherosclerosis in mice.
AB  - RATIONALE: Neutrophils have been reported to contribute to early atherosclerotic
      lesion formation. Mechanisms of neutrophil-driven atherosclerosis remain unclear
      so far. OBJECTIVE: Investigation of the role of the neutrophil granule protein
      cathelicidin (CRAMP in mouse, LL37 in human) in atherosclerosis. METHODS AND
      RESULTS: Compared to Apoe(-/-) mice, Cramp(-/-) Apoe(-/-) mice exhibit reduced
      lesion sizes with lower macrophage numbers. In atherosclerotic aortas, we could
      detect CRAMP specifically in neutrophils, but not in monocytes or macrophages. By
      use of intravital microscopy, CRAMP was found to be deposited by activated
      neutrophils on inflamed endothelium of large arteries. In this location
      cathelicidins promote adhesion of classical monocytes and neutrophils, but not
      nonclassical monocytes in a formyl-peptide receptor-dependent manner.
      CONCLUSIONS: Cathelicidins promote atherosclerosis by enhancement of the
      recruitment of inflammatory monocytes.

PMID- 22394521
TI  - Unprecedented opportunities in fall prevention for occupational therapy
      practitioners.

PMID- 22394520
TI  - Social disparities in exposures to bisphenol A and polyfluoroalkyl chemicals: a
      cross-sectional study within NHANES 2003-2006.
AB  - BACKGROUND: Bisphenol A (BPA) and polyfluoroalkyl chemicals (PFCs) are suspected
      endocrine disrupting compounds known to be ubiquitous in people's bodies.
      Population disparities in exposure to these chemicals have not been fully
      characterized. METHODS: We analyzed data from the 2003-2006 National Health and
      Nutrition Examination Survey. Using multivariable linear regression we examined
      the association between urinary concentrations of BPA, serum concentrations of
      four PFCs, and multiple measures of socioeconomic position (SEP): family income,
      education, occupation, and food security. We also examined associations with
      race/ethnicity. RESULTS: All four PFCs were positively associated with family
      income, whereas BPA was inversely associated with family income. BPA
      concentrations were higher in people who reported very low food security and
      received emergency food assistance than in those who did not. This association
      was particularly strong in children: 6-11 year-olds whose families received
      emergency food had BPA levels 54% higher (95% CI, 13 to 112%) than children of
      families who did not. For BPA and PFCs we saw smaller and less consistent
      associations with education and occupation. Mexican Americans had the lowest
      concentrations of any racial/ethnic group of both types of chemicals; for PFCs,
      Mexican Americans not born in the U.S. had much lower levels than those born in
      the U.S. CONCLUSIONS: People with lower incomes had higher body burdens of BPA;
      the reverse was true for PFCs. Family income with adjustment for family size was
      the strongest predictor of chemical concentrations among the different measures
      of SEP we studied. Income, education, occupation, and food security appear to
      capture different aspects of SEP that may be related to exposure to BPA and PFCs
      and are not necessarily interchangeable as measures of SEP in environmental
      epidemiology studies. Differences by race/ethnicity were independent of SEP.

PMID- 22394522
TI  - Telehealth opportunities in occupational therapy through the Affordable Care Act.

PMID- 22394524
TI  - Occupational therapy in fall prevention: current evidence and future directions.
AB  - Falls are a serious public health concern among older adults in the United
      States. Although many fall prevention recommendations exist, such as those
      published by the American Geriatrics Society (AGS) and the British Geriatrics
      Society (BGS) in 2010, the specific role of occupational therapy in these efforts
      is unclear. This article presents a scoping review of current published research
      documenting the role of occupational therapy in fall prevention interventions
      among community-dwelling older adults, structured by the AGS and BGS guidelines.
      We identified evidence for occupational therapy practitioner involvement in fall
      prevention in environmental modifications, exercise, and multifactorial and
      multicomponent interventions. Although research documenting the efficacy of
      occupational therapy interventions is identified as part of the Occupational
      Therapy Practice Framework: Domain and Process (2nd ed.; American Occupational
      Therapy Association, 2008), we identified little or no such research examining
      interventions to modify behaviors (e.g., fear of falling), manage postural
      hypotension, recommend appropriate footwear, and manage medications. Although
      occupational therapy is represented in the fall prevention research, the evidence
      for the profession's role in many areas is still lacking.

PMID- 22394523
TI  - Relationship between fall-related efficacy and activity engagement in community
      dwelling older adults: a meta-analytic review.
AB  - OBJECTIVE: Fear of falling can lead to restricted activity, but little is known
      about how this fear affects different aspects of people's lives. This study
      examined the relationship between fall-related efficacy (i.e., confidence or
      belief in one's ability to perform activities without losing balance or falling)
      and activity and participation. METHOD: We conducted a meta-analysis of studies
      comparing community-dwelling older adults' fall-related efficacy to measures of
      activity or participation. RESULTS: An examination of 20 cross-sectional and
      prospective studies found a strong positive relationship between fall-related
      efficacy and activity (r = .53; 95% CI [.47, .58]). An insufficient number of
      studies examining fall-related efficacy and participation were available for
      analysis. CONCLUSION: Low fall-related efficacy may be an important barrier to
      occupational engagement for many older adults and warrants careful consideration
      by occupational therapists. Future research should explore interventions that
      target fall-related efficacy and examine their effects on activity performance
      and engagement.

PMID- 22394525
TI  - Feasibility of interdisciplinary community-based fall risk screening.
AB  - OBJECTIVE: This pilot study examined the feasibility of (1) conducting
      interdisciplinary fall risk screens at a communitywide adult fall prevention
      event and (2) collecting preliminary follow-up data from people screened at the
      event about balance confidence and home and activity modifications made after
      receiving educational information at the event. METHOD: We conducted a pilot
      study with pre- and posttesting (4-mo follow-up) with 35 community-dwelling
      adults >=55 yr old. RESULTS: Approximately half the participants were at risk for
      falls. Most participants who anticipated making environmental or activity changes
      to reduce fall risk initiated changes (n = 8/11; 72.7%) during the 4-mo follow-up
      period. We found no significant difference in participants' balance confidence
      between baseline (median = 62.81) and follow-up (median = 64.06) as measured by
      the Activities-specific Balance Confidence scale. CONCLUSION: Conducting
      interdisciplinary fall risk screens at an adult fall prevention event is feasible
      and can facilitate environmental and behavior changes to reduce fall risk.

PMID- 22394526
TI  - Fear of falling and its relationship with anxiety, depression, and activity
      engagement among community-dwelling older adults.
AB  - OBJECTIVE: This study examined (1) the relationship of fear of falling to
      depression, anxiety, activity level, and activity restriction and (2) whether
      depression or anxiety predicted fear of falling, activity level, activity
      restriction, or changes in activity level. METHOD: We administered the Survey of
      Activities and Fear of Falling in the Elderly; the Geriatric Depression Scale-30;
      and the Hamilton Anxiety Scale, IVR Version, during a one-time visit to 99
      community-dwelling adults >=55 yr old. RESULTS: We found significant
      relationships between (1) fear of falling and depression, anxiety, and activity
      level; (2) depression and anxiety; and (3) activity restriction and depression.
      Activity level was negatively correlated with activity restriction, fear of
      falling, depression, and anxiety. Anxiety predicted both fear of falling and
      activity level. Both anxiety and depression predicted activity restriction
      because of fear of falling and for other reasons. CONCLUSION: Occupational
      therapy practitioners should consider screening their older adult clientele for
      fear of falling, anxiety, and depression because these states may lead to fall
      risk and activity restriction.

PMID- 22394527
TI  - Sense and self-regulation checklist, a measure of comorbid autism symptoms:
      initial psychometric evidence.
AB  - Sensory and self-regulatory symptoms make up most of the comorbid symptoms in
      autism and are associated with increased autism severity. We validated a parent
      caregiver measure of comorbid symptoms in autism, the Sense and Self-Regulation
      Checklist (SSC), in 265 children <6 yr with typical development (n = 138), autism
      (n = 99), or other developmental delay (n = 28); Cronbach's alpha was .87. We
      report two new findings discriminating autism from other groups: (1) multifocal
      tactile sensory impairment, characterized by hyporeactivity to injurious stimuli
      and hyperreactivity to noninjurious stimuli (F[2, 262] = 86.8, p < .001) and (2)
      global self-regulatory delay (F[2, 262] = 122, p < .001). Both findings suggest
      an explanation for social delay in children with autism. The SSC reports a
      prevalence of sensory and self-regulatory findings approaching 100% in the autism
      group (96% and 98%, respectively), raising the possibility that sensory and self
      regulatory difficulties represent a core part of autism.

PMID- 22394528
TI  - Outcome moderators of a fatigue management program for people with multiple
      sclerosis.
AB  - OBJECTIVE: We determined whether age, gender, work status, or impairment
      moderated fatigue management program outcomes for people with multiple sclerosis
      (MS). METHOD: We conducted a secondary analysis of longitudinal data from a
      randomized controlled trial using mixed-effects models (N = 181) and examined
      outcomes of fatigue impact, mental health, physical health, and self-efficacy.
      Measures were collected before and immediately after intervention and at 6 wk, 3
      mo, and 6 mo postintervention. RESULTS: Younger participants experienced greater
      reductions in fatigue impact and greater improvements in self-efficacy over time
      than did older participants, but we found no age differences in physical or
      mental health. Participants with less impairment experienced greater mental
      health gains and were more likely to retain these gains over time than were
      participants with greater impairment. Although women experienced greater fatigue
      impact benefits, men experienced greater mental health benefits. Work status did
      not moderate outcomes. CONCLUSION: Fatigue management program outcomes for people
      with MS are moderated by age, gender, and impairment.

PMID- 22394529
TI  - Pilot comparative study of unilateral and bilateral robot-assisted training on
      upper-extremity performance in patients with stroke.
AB  - We compared a unilateral robot-assisted training protocol (URTP) and a bilateral
      robot-assisted training protocol (BRTP) to study their differential effects. We
      recruited 21 patients with stroke who received 90-105 min of therapy 5 days/wk
      for 4 wk. Participants in the URTP and BRTP groups practiced forearm pronation
      and supination and wrist flexion and extension in a simultaneous manner with the
      Bi-Manu-Track. The control group received standard rehabilitation. Clinical
      measures included the Fugl-Meyer Assessment, the Medical Research Council
      instrument, grip strength, and the Modified Ashworth Scale to assess motor
      impairment, muscle power, muscle strength, and spasticity, respectively. The
      pilot study indicated that the URTP and BRTP might have differential benefits for
      movement improvement. URTP might be a more compelling approach to improving upper
      limb motor impairment, muscle power, and strength at the distal joints than BRTP,
      whereas BRTP could be an optimal approach to improving proximal muscle power.

PMID- 22394530
TI  - Dynamic Lowenstein Occupational Therapy Cognitive Assessment: evaluation of
      potential to change in cognitive performance.
AB  - OBJECTIVE: We studied the psychometric properties of the dynamic version of the
      Lowenstein Occupational Therapy Cognitive Assessment (DLOTCA) and examined the
      most frequent level of mediation used for planning for intervention. METHOD:
      Participants included 83 clients hospitalized after first stroke (mean age =
      57.7, standard deviation = 8.33) and 45 healthy control participants. All were
      assessed with the DLOTCA after providing informed consent. RESULTS: Interrater
      reliability showed high correlations between all pairs of raters. Internal
      consistency reliability showed moderate to high alphas (.602-.813) for all
      domains except Visual Perception. We found significant differences between the
      groups of participants before mediation; both benefited from mediation, showing
      moderate to high effect sizes. Stroke clients needed higher levels of mediation.
      CONCLUSION: The DLOTCA is effective in providing insight into whether
      participants need mediation and the level and type of assistance they require.
      The DLOTCA provides guidance for planning intervention for people with cognitive
      disabilities.

PMID- 22394531
TI  - Impact of vision impairment on intensity of occupational therapy utilization and
      outcomes in subacute rehabilitation.
AB  - OBJECTIVE: To examine whether vision impairment is a predictor of intensity of
      occupational therapy utilization and outcomes in a sample of older adults ages
      >=55 receiving subacute rehabilitation in a long-term care setting. METHOD: Data
      for this cohort study were collected by means of structured, in-person interviews
      with 100 older adult rehabilitation patients at admission to a subacute unit in a
      long-term care facility and by medical chart review after discharge. RESULTS:
      Regression analyses indicated that after controlling for sociodemographic,
      health, and social support variables, worse contrast sensitivity was a
      significant predictor of decreased time in occupational therapy, and worse visual
      acuity was a significant predictor of higher functional dependency at discharge.
      CONCLUSION: Vision impairment may prevent full use of occupational therapy and
      hinder occupational therapy efficacy in subacute care settings. Study findings
      underscore the importance of developing low vision rehabilitation interventions
      that can be delivered in conjunction with more traditional subacute
      rehabilitation.

PMID- 22394532
TI  - Effect of an occupation-based cultural heritage intervention in long-term
      geriatric care: a two-group control study.
AB  - OBJECTIVE: We investigated the effectiveness of an occupation-based cultural
      heritage intervention to facilitate adaptation to relocation into long-term care
      (LTC) facilities as measured by quality of life, activity engagement, and social
      participation. METHOD: We used a quasi-experimental nonequivalent control group
      design with pre- and posttests. Residents receiving the cultural intervention
      were compared with residents in a typical activity group. Eight sessions, two per
      week for 4 wk, were facilitated by certified occupational therapy assistants.
      RESULTS: Twenty-nine participants completed the group sessions. Quality-of-life
      scores improved significantly over time for both groups. Statistically, a greater
      percentage of time was spent in discretionary than obligatory time, pretest and
      posttest, with no significant difference between groups. CONCLUSION: The study
      demonstrated effectiveness of a structured, occupation-based social group
      intervention that improved quality of life, an indicator of adaptation. It also
      provided a description of activity patterns and social participation of LTC
      residents.

PMID- 22394533
TI  - Psychometrics of the self-report safe driving behavior measure for older adults.
AB  - We investigated the psychometric properties of the 68-item Safe Driving Behavior
      Measure (SDBM) with 80 older drivers, 80 caregivers, and 2 evaluators from two
      sites. Using Rasch analysis, we examined unidimensionality and local dependence;
      rating scale; item- and person-level psychometrics; and item hierarchy of older
      drivers, caregivers, and driving evaluators who had completed the SDBM. The
      evidence suggested the SDBM is unidimensional, but pairs of items showed local
      dependency. Across the three rater groups, the data showed good person (>=3.4)
      and item (>=3.6) separation as well as good person (>=.93) and item reliability
      (>=.92). Cronbach's alpha was >=.96, and few items were misfitting. Some of the
      items did not follow the hypothesized order of item difficulty. The SDBM
      classified the older drivers into six ability levels, but to fully calibrate the
      instrument it must be refined in terms of its items (e.g., item exclusion) and
      then tested among participants of lesser ability.

PMID- 22394534
TI  - Randomized controlled trial of daily total end range time (TERT) for Capener
      splinting of the stiff proximal interphalangeal joint.
AB  - OBJECTIVE: Capener splinting is a common treatment for extension deficit of the
      proximal interphalangeal (PIP) joint. This study compared the effect of daily
      splint total end range time (TERT) of 6-12 hr versus 12-16 hr. METHOD: Twenty-two
      participants with extension deficits of the PIP joint were randomly allocated to
      a daily TERT of 6-12 hr or 12-16 hr. Progress after 8 wk of splinting was
      evaluated. RESULTS: No significant difference was found in change in extension
      range of motion (ROM) between groups (active ROM, F[4, 17] = 2.19, p = .13;
      passive ROM, F[4, 17] = 0.95, p = .46; torque ROM, F[4, 17] = 1.49, p = .26).
      Considerable crossover between groups resulted in a similar average daily TERT
      (9.5 hr for the 6-12 hr group vs. 11.5 hr for the 12-16 hr group). CONCLUSION:
      Further research with a larger sample is needed to determine whether longer daily
      TERT is beneficial. Our results suggest, however, that most patients find it
      difficult to wear splints >12 hr/day.

PMID- 22394535
TI  - Comparison of the occupational therapy research agenda with the National
      Institutes of Health Roadmap for Medical Research.

PMID- 22394538
TI  - State of mental health research in the American Journal of Occupational Therapy,
      2008-2011.
AB  - In this article, I examine the state of mental health research in the American
      Journal of Occupational Therapy from 2008 to 2011. Although other practice areas
      have seen an increase in the number and rigor of intervention effectiveness
      studies, mental health occupational therapy research has been insufficient to
      support the profession's role in traditional mental health services. Strategies
      to enhance the profession's role in mental health practice are suggested and
      include using occupational therapy behavioral health management research in
      school-based and transition services to support occupational therapy's role in
      traditional mental health practice settings.

PMID- 22394537
TI  - Measurement characteristics of the engagement in meaningful activities survey in
      an age-diverse sample.
AB  - OBJECTIVE: This study evaluated the measurement characteristics of the Engagement
      in Meaningful Activities Survey (EMAS) in an age-diverse sample. METHOD: The
      sample included 154 older adults and 122 college students (age range = 18-100
      yr). A Rasch-Andrich rating scale model was used to evaluate the EMAS. Analyses
      addressed rating scale design, person and item fit, item hierarchy, model
      unidimensionality, and differential item functioning. RESULTS: Category
      functioning was improved by reducing the EMAS item responses to four categories.
      Adequate person response validity was established, and all but one EMAS item
      demonstrated an ideal fit to the Rasch measurement model. After establishing the
      item hierarchy, I found the EMAS to be a unidimensional measure. Differential
      item functioning was not detected using Bonferroni-adjusted statistical criteria.
      CONCLUSION: The results confirm the potential to validly measure subjective
      qualities of meaningful activity participation. The EMAS can be used to evaluate
      processes and outcomes central to occupational therapy practice and to aid in the
      design of therapeutic occupations.

PMID- 22394539
TI  - Proteomic analysis of ophthalmic disease.
AB  - Proteomics, a highly sophisticated way to study the protein profile of various
      biological tissues or fluids, has hitherto had a relatively limited role
      ophthalmic science. Of the few proteomic studies that have been performed, liquid
      chromatography, electrophoresis gel separation and mass spectrometry have been
      utilized to investigate the proteome of several different eye structures and
      fluids from both humans and animal models. Ophthalmic proteomic studies have so
      far attempted to identify proteins unique to the eye, to investigate protein
      changes due to the onset of various diseases and to identify proteins that could
      act as markers of disease. Proteomics has the potential to improve the way in
      which eye disease is diagnosed and potentially even treated by identifying novel
      pathogenic pathways that may be susceptible to therapeutic manipulation. The aim
      of this review is to give an overview the current and potential application of
      proteomic science to ophthalmic research.

PMID- 22394540
TI  - Cranial and related sensorimotor impairments in rodent models of Parkinson's
      disease.
AB  - In Parkinson's disease both limb and cranial sensorimotor functions are impaired,
      leading to a profound diminished quality of life for many patients. Toxin and
      genetic animal models of Parkinson's disease are likely essential for
      understanding the pathology associated with these impairments as well as for the
      development and testing of potential therapeutics. Here we describe useful novel
      and established behavioral outcome measures for assessing limb and cranial
      sensorimotor functions in toxin and genetic models of parkinsonism in rats and
      mice.

PMID- 22394541
TI  - A scientist's dilemma: follow my hypothesis or my findings?
AB  - Over the course of my 50 years of brain-behavioral research, choicepoints
      presented themselves as to either follow my original hypothesis or follow my
      puzzling empirical findings. I trusted the latter more than the former because I
      believe it is where reality is to be found. Phil Teitelbaum's teachings had a
      major influence on those decisions. In the present essay, I describe the
      evolution of those choicepoints that led me from studies of hormone-brain
      behavior interactions to a rhythmical brain-behavior connection, to sexual
      behavior, pain blockage, human brain-behavior interactions, and human brain
      imaging. Along this tortuous course, I learned that vaginal stimulation can block
      pain, the vagus nerve apparently can convey genital sensory activity to the
      brain, bypassing spinal cord injury, and all major brain systems evidently
      contribute to women's orgasm. An important message I learned is: pay attention to
      what you observe in your experiments, and have the courage to follow it up,
      particularly if what you observe is not what you were looking for...because it,
      rather than your hypothesis, is more likely to reveal reality.

PMID- 22394542
TI  - The match/mismatch of visuo-spatial cues between acquisition and retrieval
      contexts influences the expression of response vs. place memory in rats.
AB  - Animals can perform goal-directed tasks by using response cues or place cues. The
      underlying memory systems are occasionally presented as competing. Using the
      double-H maze test (Pol-Bodetto et al.), we trained rats for response learning
      and, 24 h later, tested their memory in a 60-s probe trial using a new start
      place. A modest shift of the start place (translation: 60-cm to the left)
      provided a high misleading potential, whereas a marked shift (180 degrees 
      rotation; shift to the opposite) provided a low misleading potential. We analyzed
      each rat's first arm choice (to assess response vs. place memory retrieval) and
      its subsequent search for the former platform location (to assess the persistence
      in place memory or the shift from response to place memory). After the
      translation, response memory-based behavior was found in more than 90% rats
      (24/26). After the rotation, place memory-based behavior was observed in 50%
      rats, the others showing response memory or failing. Rats starting to use
      response cues were nevertheless able to subsequently shift to place ones. A
      posteriori behavioral analyses showed more and longer stops in rats starting
      their probe trial on the basis of place (vs. response) cues. These observations
      qualify the idea of competing memory systems for responses and places and are
      compatible with that of a cooperation between both systems according to
      principles of match/mismatch computation (at the start of a probe trial) and of
      error-driven adjustment (during the ongoing probe trial).

PMID- 22394544
TI  - Water tubing-related injuries treated in US emergency departments, 1991-2009.
AB  - BACKGROUND: The objective was to describe the patterns and mechanisms of water
      tubing-related injuries treated in U.S. emergency departments. METHODS: The
      National Electronic Injury Surveillance System was used to examine cases of water
      tubing-related injuries. Sample weights were used to calculate national estimates
      of water tubing-related injuries. Analyses were conducted in 2010. RESULTS: From
      1991-2009 an estimated 69,471 injuries were treated in US emergency departments
      for water tubing-related injuries. The annual number of cases increased 250% over
      the 19-year study period (P < .001). Sprains and strains accounted for the
      largest portion of injuries (27.2%). The head was the most frequently injured
      body part (27.5%). Children and adolescents <= 19 years were more likely to be
      injured by contact with another person (OR: 2.47; 95% CI = 1.61-3.80) and were
      more likely to sustain injuries to the head (OR: 2.61; 95% CI = 2.01-3.38)
      compared with adults. Adults >= 20 years, were more likely than individuals <= 19
      years to sustain sprains and strains (OR: 2.11; 95% CI = 1.64-2.71) and were most
      commonly injured by impact with the water (54.6%). CONCLUSIONS: Patterns of water
      tubing-related injuries differ for children and adults. Research is needed to
      determine how best to reduce these injuries.

PMID- 22394543
TI  - C57Bl/6 N mice on a western diet display reduced intestinal and hepatic
      cholesterol levels despite a plasma hypercholesterolemia.
AB  - BACKGROUND: Small intestine and liver greatly contribute to whole body lipid,
      cholesterol and phospholipid metabolism but to which extent cholesterol and
      phospholipid handling in these tissues is affected by high fat Western-style
      obesogenic diets remains to be determined. METHODS: We therefore measured
      cholesterol and phospholipid concentration in intestine and liver and quantified
      fecal neutral sterol and bile acid excretion in C57Bl/6 N mice fed for 12 weeks
      either a cholesterol-free high carbohydrate control diet or a high fat Western
      diet containing 0.03% (w/w) cholesterol. To identify the underlying mechanisms of
      dietary adaptations in intestine and liver, changes in gene expression were
      assessed by microarray and qPCR profiling, respectively. RESULTS: Mice on Western
      diet showed increased plasma cholesterol levels, associated with the higher
      dietary cholesterol supply, yet, significantly reduced cholesterol levels were
      found in intestine and liver. Transcript profiling revealed evidence that
      expression of numerous genes involved in cholesterol synthesis and uptake via
      LDL, but also in phospholipid metabolism, underwent compensatory regulations in
      both tissues. Alterations in glycerophospholipid metabolism were confirmed at the
      metabolite level by phospolipid profiling via mass spectrometry. CONCLUSIONS: Our
      findings suggest that intestine and liver react to a high dietary fat intake by
      an activation of de novo cholesterol synthesis and other cholesterol-saving
      mechanisms, as well as with major changes in phospholipid metabolism, to
      accommodate to the fat load.

PMID- 22394545
TI  - Functional characterization of naturally occurring transglutaminase 2 mutants
      implicated in early-onset type 2 diabetes.
AB  - Transglutaminase 2 (TG2) is an enzyme with diverse biological functions. TG2
      catalyzes transamidation reactions, has intrinsic kinase activity, and acts as a
      G-protein in intracellular signaling. TG2 (Tgm2)-null mice are glucose intolerant
      and have impaired glucose-stimulated insulin secretion (GSIS). Furthermore, three
      naturally occurring missense mutations in the human TGM2 gene, corresponding to
      amino acid substitutions of Met330Arg, Ile331Asn, and Asn333Ser in the TG2
      protein, have been reported and found to be associated with early-onset type 2
      diabetes. However, their effect on TG2 function is not fully understood. To
      determine this, we have reproduced naturally occurring mutations in TG2 using
      site-directed mutagenesis. Overexpression of Myc-TG2 mutants in INS-1E cells
      resulted in a reduction of GSIS in comparison with cells overexpressing wild-type
      Myc-TG2 (WT-TG2). The maximum reduction was found in cells overexpressing
      Ile331Asn-TG2 (32%) followed by Met330Arg-TG2 (20%), and the least in Asn333Ser
      TG2 (7%). Enzymatic analysis revealed that TG2 mutants have impaired
      transamidation and kinase activities in comparison with WT-TG2. GTP-binding
      assays showed that TG2 mutants also have altered GTP-binding ability, which is
      found to be modulated in response to glucose stimulation. Collectively, these
      data suggest that naturally occurring mutations in TG2 affect transamidation,
      kinase, and GTP-binding functions of TG2. While reduced insulin secretion, as a
      result of naturally occurring mutations in TG2, is due to the impairment of more
      than one biological function of TG2, it is the transamidation function that
      appears to be impaired during the first phase, whereas the GTP-binding function
      affects the second phase of insulin secretion.

PMID- 22394546
TI  - Initially fewer bloodstream infections for allogeneic vs. autologous stem-cell
      transplants in neutropenic patients.
AB  - Chemotherapy and/or radiotherapy used as conditioning regimens before autologous
      or allogeneic haematopoietic cell transplantations (HCTs) cause neutropenia,
      which is the main reason for bloodstream infections. Autologous HCTs are
      considered to be superior to allogeneic HCTs in terms of infection outcome. A
      previous analysis suggested that patients with allogeneic HCTs are exposed to a
      reduced infection hazard and that an unfavourable infection outcome of allogeneic
      HCTs may be mediated through prolonged neutropenia. Therefore, we investigated
      whether allogeneic HCTs initially lead to fewer infections. We evaluated data
      from a prospective non-randomized multi-centre cohort study, with a total of 1616
      patients. Of these, 703 patients received autologous and 913 patients received
      allogeneic HCTs from January 2000 to June 2004. The retrospective analysis used
      simultaneous confidence bands for the cumulative infection probability in the
      presence of competing risks. Patients with allogeneic HCTs experienced fewer
      infections during the early phase of neutropenia. As patients with autologous
      HCTs are not necessarily subject to antibiotic prophylaxis, a future study should
      investigate this policy. A limitation of the analysis is that it did not find the
      effect of crossing cumulative infection probabilities to be significant.

PMID- 22394547
TI  - Comparison of the behavioural and histological characteristics of the 6-OHDA and
      alpha-synuclein rat models of Parkinson's disease.
AB  - Development of relevant models of Parkinson's disease (PD) is essential for a
      better understanding of the pathological processes underlying the human disease
      and for the evaluation of promising targets for therapeutic intervention. To
      date, most pre-clinical studies have been performed in the well-established
      rodent and non-human primate models using injection of 6-hydroxydopamine (6-OHDA)
      or 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP). Overexpression of the
      disease-causing protein alpha-synuclein (alpha-syn), using adeno-associated viral
      (AAV) vectors, has provided a novel model that recapitulates many features of the
      human disease. In the present study we compared the AAV-alpha-syn rat model with
      models where the nigro-striatal pathway is lesioned by injection of 6-OHDA in the
      striatum (partial lesion) or the medial forebrain bundle (full lesion).
      Examination of the behavioural changes over time revealed a different progression
      and magnitude of the motor impairment. Interestingly, dopamine (DA) neuron loss
      is prominent in both the toxin and the AAV-alpha-syn models. However, alpha-syn
      overexpressing animals were seen to exhibit less cell and terminal loss for an
      equivalent level of motor abnormalities. Prominent and persistent axonal
      pathology is only observed in the alpha-syn rat model. We suggest that, while
      neuronal and terminal loss mainly accounts for the behavioural impairment in the
      toxin-based model, similar motor deficits result from the combination of cell
      death and dysfunction of the remaining nigro-striatal neurons in the AAV-alpha
      syn model. While the two models have been developed to mimic DA neuron
      deficiency, they differ in their temporal and neuropathological characteristics,
      and replicate different aspects of the pathophysiology of the human disease. This
      study suggests that the AAV-alpha-syn model replicates the human pathology more
      closely than either of the other two 6-OHDA lesion models.

PMID- 22394549
TI  - Superimposed high-frequency jet ventilation combined with continuous positive
      airway pressure/assisted spontaneous breathing improves oxygenation in patients
      with H1N1-associated ARDS.
AB  - BACKGROUND: Numerous cases of swine-origin 2009 H1N1 influenza A virus (H1N1)
      associated acute respiratory distress syndrome (ARDS) bridged by extracorporeal
      membrane oxygenation (ECMO) therapy have been reported; however, complication
      rates are high. We present our experience with H1N1-associated ARDS and
      successful bridging of lung function using superimposed high-frequency jet
      ventilation (SHFJV) in combination with continuous positive airway
      pressure/assisted spontaneous breathing (CPAP/ASB). METHODS: We admitted five
      patients with H1N1 infection and ARDS to our intensive care unit. Although all
      patients required pure oxygen and controlled ventilation, oxygenation was
      insufficient. We applied SHFJV/CPAP/ASB to improve oxygenation. RESULTS: Initial
      PaO2/FiO2 ratio prior SHFJV was 58-79 mmHg. In all patients, successful
      oxygenation was achieved by SHFJV (PaO2/FiO2 ratio 105-306 mmHg within 24 h).
      Spontaneous breathing was set during first hours after admission. SHFJV could be
      stopped after 39, 40, 72, 100, or 240 h. Concomitant pulmonary herpes simplex
      virus (HSV) infection was observed in all patients. Two patients were
      successfully discharged. The other three patients relapsed and died within 7
      weeks mainly due to combined HSV infection and in two cases reoccurring H1N1
      infection. CONCLUSIONS: SHFJV represents an alternative to bridge lung function
      successfully and improve oxygenation in the critically ill.

PMID- 22394550
TI  - Systematic review of complications of tonsillotomy versus tonsillectomy.
AB  - OBJECTIVE: Intracapsular tonsillotomy continues to gain acceptance as an
      alternative to traditional tonsillectomy. Despite large clinical studies, there
      is a lack of consensus as to which technique offers lower complication rates.
      This study seeks to analyze the available data and surmise the complication rates
      of partial tonsillectomy as compared with traditional tonsillectomy. Data
      Sources. MEDLINE was searched using multiple search terms. REVIEW METHODS: After
      the MEDLINE search, the following inclusion criteria were applied: English
      language, human subjects, and related to partial tonsillectomy. Multiple
      tonsillotomy techniques were included. The results of these studies were summated
      and the results analyzed. Subgroup analysis was then performed. RESULTS: Thirty
      three studies met inclusion criteria. Tonsillotomy had a lower postoperative
      bleeding rate, lower postoperative dehydration rate requiring medical care,
      reduced days of analgesic use, and reduced days to return to normal diet compared
      with tonsillectomy. When separated into higher versus lower quality studies, the
      differences in bleeding and dehydration were negligible, while differences in
      return to diet and days of analgesic use persisted. Mean intraoperative blood
      loss was similar for both techniques. Insufficient data were available to assess
      tonsil regrowth rates. CONCLUSIONS: Tonsillotomy appears to be a safe technique
      that may offer some advantages over tonsillectomy in terms of postoperative
      morbidity, but differences in hemorrhage and dehydration were not evident in high
      quality studies. Data regarding tonsil regrowth rates and efficacy in treating
      sleep-disordered breathing are not yet sufficient for formal analysis, which may
      preclude widespread acceptance of this technique.

PMID- 22394551
TI  - No evidence for the diagnostic value of Borrelia serology in patients with sudden
      hearing loss.
AB  - In this evidence-based case report, we address the following clinical question:
      What is the predictive value of serological testing for Borrelia for diagnosing
      neuroborreliosis in patients with sudden sensorineural hearing loss? We searched
      for relevant articles in PubMed, Embase, and Web of Science. We retrieved 49
      unique publications and screened the title and abstract of these articles for
      relevance. We included 2 of 12 studies initially considered relevant to answer
      our question. These 2 studies reported a seroprevalence of antibodies against
      Borrelia of 16% in patients with sudden sensorineural hearing loss (SHL) as
      compared with 13.5% in the general population, but in neither patients with
      definite neuroborreliosis were they found. To date, there is no evidence
      regarding the added value of routine diagnostic serologic testing for Borrelia in
      diagnosing neuroborreliosis in patients with sudden SHL. Neuroborreliosis seems
      to be a rare cause of sudden SHL, and routine screening of patients for borrelia
      antibodies in serum should therefore not be recommended.

PMID- 22394548
TI  - Iodine-125 brachytherapy for brain tumours--a review.
AB  - Iodine-125 brachytherapy has been applied to brain tumours since 1979. Even
      though the physical and biological characteristics make these implants
      particularly attractive for minimal invasive treatment, the place for
      stereotactic brachytherapy is still poorly defined.An extensive review of the
      literature has been performed, especially concerning indications, results and
      complications. Iodine-125 seeds have been implanted in astrocytomas I-III,
      glioblastomas, metastases and several other tumour entities. Outcome data given
      in the literature are summarized. Complications are rare in carefully selected
      patients.All in all, for highly selected patients with newly diagnosed or
      recurrent primary or metastatic tumours, this method provides encouraging
      survival rates with relatively low complication rates and a good quality of life.

PMID- 22394552
TI  - Is it really a thyroid nodule? Another cause of a lower midline neck mass.

PMID- 22394553
TI  - Strength of titanium intramedullary implant versus miniplate fixation of
      mandibular condyle fractures.
AB  - OBJECTIVE: To test the strength of internal fixation of mandibular condyle
      fractures repaired with titanium miniplates versus titanium intramedullary
      implants. STUDY DESIGN: Prospective laboratory experimentation in urethane
      mandible models and human cadaveric mandibles. SETTING: Materials testing
      laboratory at an academic medical center. METHODS: Osteotomies of the mandibular
      condyle were created in 40 urethane hemimandible models and 24 human cadaveric
      specimens. Half of the samples in each group were repaired with traditional
      miniplates, and the other half were repaired with intramedullary titanium
      implants. Anteroposterior and mediolateral loads were applied to the samples, and
      the displacement was measured with reference to the applied force. RESULTS:
      Titanium intramedullary implants demonstrated statistically significant improved
      strength and stiffness versus miniplates in the urethane model experimental
      groups. Despite frequent plastic deformation and mechanical failures of the
      miniplates, a 1.6-mm-diameter titanium intramedullary pin did not mechanically
      fail in any of the cases. Intramedullary implantation failures were due to
      secondary fracture of the adjacent cortical bone or experimental design
      limitations including rotation of the smooth pin implant. CONCLUSION: Mechanical
      implant failures that were encountered with miniplate fixation were not seen with
      titanium intramedullary implants. These intramedullary implants provide stronger
      and more rigid fixation of mandibular condyle fractures than miniplates in this
      in vitro model.

PMID- 22394554
TI  - Density functional theory-based simulations of sum frequency generation spectra
      involving methyl stretching vibrations: effect of the molecular model on the
      deduced molecular orientation and comparison with an analytical approach.
AB  - The knowledge of the first hyperpolarizability tensor elements of molecular
      groups is crucial for a quantitative interpretation of the sum frequency
      generation (SFG) activity of thin organic films at interfaces. Here, the SFG
      response of the terminal methyl group of a dodecanethiol (DDT) monolayer has been
      interpreted on the basis of calculations performed at the density functional
      theory (DFT) level of approximation. In particular, DFT calculations have been
      carried out on three classes of models for the aliphatic chains. The first class
      of models consists of aliphatic chains, containing from 3 to 12 carbon atoms, in
      which only one methyl group can freely vibrate, while the rest of the chain is
      frozen by a strong overweight of its C and H atoms. This enables us to localize
      the probed vibrational modes on the methyl group. In the second class, only one
      methyl group is frozen, while the entire remaining chain is allowed to vibrate.
      This enables us to analyse the influence of the aliphatic chain on the methyl
      stretching vibrations. Finally, the dodecanethiol (DDT) molecule is considered,
      for which the effects of two dielectrics, i.e. n-hexane and n-dodecane, are
      investigated. Moreover, DDT calculations are also carried out by using different
      exchange-correlation (XC) functionals in order to assess the DFT approximations.
      Using the DFT IR vectors and Raman tensors, the SFG spectrum of DDT has been
      simulated and the orientation of the methyl group has then been deduced and
      compared with that obtained using an analytical approach based on a bond
      additivity model. This analysis shows that when using DFT molecular properties,
      the predicted orientation of the terminal methyl group tends to converge as a
      function of the alkyl chain length and that the effects of the chain as well as
      of the dielectric environment are small. Instead, a more significant difference
      is observed when comparing the DFT-based results with those obtained from the
      analytical approach, thus indicating the importance of a quantum chemical
      description of the hyperpolarizability tensor elements of the methyl group.

PMID- 22394556
TI  - Sorption of triazine and organophosphorus pesticides on soil and biochar.
AB  - Sorption and degradation are the primary processes controlling the efficacy and
      runoff contamination risk of agrochemicals. Considering the longevity of biochar
      in agroecosystems, biochar soil amendment must be carefully evaluated on the
      basis of the target agrochemical and soil types to achieve agricultural (minimum
      impact on efficacy) and environmental (minimum runoff contamination) benefits. In
      this study, sorption-desorption isotherms and kinetics of triazine
      (deisopropylatrazine) and organophosphorus (malathion, parathion, and diazinon)
      pesticides were first investigated on various soil types ranging from clayey,
      acidic Puerto Rican forest soil (PR) to heavy metal contaminated small arms range
      (SAR) soils of sandy and peaty nature. On PR, malathion sorption did not reach
      equilibrium during the 3 week study. Comparison of solution-phase molar
      phosphorus and agrochemical concentrations suggested that degradation products of
      organophosphorus pesticides were bound on soil surfaces. The degree of sorption
      on different soils showed the following increasing trend: deisopropylatrazine <
      malathion < diazinon < parathion. While sorption of deisopropylatrazine on SAR
      soils was not affected by diazinon or malathion, deisopropylatrazine suppressed
      the sorption of diazinon and malathion. Deisopropylatrazine irreversibly sorbed
      on biochars, and greater sorption was observed with higher Brunauer-Emmett-Teller
      surface area of biochar (4.7-2061 mg g(-1)). The results suggested the utility of
      biochar for remediation of sites where concentrations of highly stable and mobile
      agrochemicals exceed the water-quality benchmarks.

PMID- 22394555
TI  - Therapeutic use of a cationic antimicrobial peptide from the spider
      Acanthoscurria gomesiana in the control of experimental candidiasis.
AB  - BACKGROUND: Antimicrobial peptides are present in animals, plants and
      microorganisms and play a fundamental role in the innate immune response. Gomesin
      is a cationic antimicrobial peptide purified from haemocytes of the spider
      Acanthoscurria gomesiana. It has a broad-spectrum of activity against bacteria,
      fungi, protozoa and tumour cells. Candida albicans is a commensal yeast that is
      part of the human microbiota. However, in immunocompromised patients, this fungus
      may cause skin, mucosal or systemic infections. The typical treatment for this
      mycosis comprises three major categories of antifungal drugs: polyenes, azoles
      and echinocandins; however cases of resistance to these drugs are frequently
      reported. With the emergence of microorganisms that are resistant to conventional
      antibiotics, the development of alternative treatments for candidiasis is
      important. In this study, we evaluate the efficacy of gomesin treatment on
      disseminated and vaginal candidiasis as well as its toxicity and biodistribution.
      RESULTS: Treatment with gomesin effectively reduced Candida albicans in the
      kidneys, spleen, liver and vagina of infected mice. The biodistribution of
      gomesin labelled with technetium-99 m showed that the peptide is captured in the
      kidneys, spleen and liver. Enhanced production of TNF-alpha, IFN-gamma and IL-6
      was detected in infected mice treated with gomesin, suggesting an
      immunomodulatory activity. Moreover, immunosuppressed and C. albicans-infected
      mice showed an increase in survival after treatment with gomesin and fluconazole.
      Systemic administration of gomesin was also not toxic to the mice. CONCLUSIONS:
      Gomesin proved to be effective against experimental Candida albicans infection.
      It can be used as an alternative therapy for candidiasis, either alone or in
      combination with fluconazole. Gomesin's mechanism is not fully understood, but we
      hypothesise that the peptide acts through the permeabilisation of the yeast
      membrane leading to death and/or releasing the yeast antigens that trigger the
      host immune response against infection. Therefore, data presented in this study
      reinforces the potential of gomesin as a therapeutic antifungal agent in both
      humans and animals.

PMID- 22394557
TI  - Increasing antagonistic interactions cause bacterial communities to collapse at
      high diversity.
AB  - Biodiversity is a major determinant of ecosystem functioning. Species-rich
      communities often use resources more efficiently thereby improving community
      performance. However, high competition within diverse communities may also reduce
      community functioning. We manipulated the genotypic diversity of Pseudomonas
      fluorescens communities, a plant mutualistic species inhibiting pathogens. We
      measured antagonistic interactions in vitro, and related these interactions to
      bacterial community productivity (root colonisation) and ecosystem service (host
      plant protection). Antagonistic interactions increased disproportionally with
      species richness. Mutual poisoning between competitors lead to a 'negative
      complementarity effect', causing a decrease in bacterial density by up to 98% in
      diverse communities and a complete loss of plant protection. The results
      emphasize that antagonistic interactions may determine community functioning and
      cause negative biodiversity-ecosystem functioning relationships. Interference
      competition may thus be an additional key for predicting the dynamics and
      performance of natural assemblages and needs to be implemented in future
      biodiversity models.

PMID- 22394558
TI  - Pakistan's deadly cocktail of substandard drugs.

PMID- 22394559
TI  - Thyrotoxicosis.
AB  - Thyrotoxicosis is a common disorder, especially in women. The most frequent cause
      is Graves' disease (autoimmune hyperthyroidism). Other important causes include
      toxic nodular hyperthyroidism, due to the presence of one or more autonomously
      functioning thyroid nodules, and thyroiditis caused by inflammation, which
      results in release of stored hormones. Antithyroid drugs are the usual initial
      treatment (thionamides such as carbimazole or its active metabolite methimazole
      are the drugs of choice). A prolonged course leads to remission of Graves'
      hyperthyroidism in about a third of cases. Because of the low remission rate in
      Graves' disease and the inability to cure toxic nodular hyperthyroidism with
      antithyroid drugs alone, radioiodine is increasingly used as first line therapy,
      and is the preferred choice for relapsed Graves' hyperthyroidism. Total
      thyroidectomy is an option in selected cases. Future efforts are likely to
      concentrate on novel and safe ways to modulate the underlying disease process
      rather than stopping excess thyroid hormone production.

PMID- 22394560
TI  - The STING in the tail for cytosolic DNA-dependent activation of IRF3.
AB  - Cytosolic pattern recognition receptors (PRRs) sense intracellular nucleic acids
      from pathogens such as bacteria and viruses, which leads to the induction of type
      I interferon (IFN) responses that are essential for an effective immune response.
      Further, these PRR pathways can be aberrantly activated by self DNA, which leads
      to autoimmunity. Therefore, understanding the signaling mechanisms that underlie
      PRR-induced production of IFN is vital to health and disease. A key transcription
      factor that is involved in these pathways is IFN regulatory factor 3 (IRF3),
      which is often activated by the kinase TANK-binding kinase 1 (TBK1). STING
      (stimulator of interferon genes) is a master regulator for the cyto-solic nucleic
      acid-mediated activation of IRF3 through TBK1 stimulation, but how the STING-TBK1
      IRF3 signaling axis operates has been unclear. A study now shows that in response
      to cytosolic double-stranded DNA, the C-terminal tail of STING provides a
      scaffold to assemble IRF3 and TBK1, which leads to TBK1-dependent phosphorylation
      of IRF3. Thus, STING directs TBK1 to activate IRF3 in DNA-sensing pathways.

PMID- 22394561
TI  - Akt and ERK control the proliferative response of mammary epithelial cells to the
      growth factors IGF-1 and EGF through the cell cycle inhibitor p57Kip2.
AB  - Epithelial cells respond to growth factors including epidermal growth factor
      (EGF), insulin-like growth factor 1 (IGF-1), and insulin. Using high-content
      immunofluorescence microscopy, we quantitated differences in signaling networks
      downstream of EGF, which stimulated proliferation of mammary epithelial cells,
      and insulin or IGF-1, which enhanced the proliferative response to EGF but did
      not stimulate proliferation independently. We found that the abundance of the
      cyclin-dependent kinase inhibitors p21Cip1 and p57Kip2 increased in response to
      IGF-1 or insulin but decreased in response to EGF. Depletion of p57Kip2, but not
      p21Cip1, rendered IGF-1 or insulin sufficient to induce cellular proliferation in
      the absence of EGF. Signaling through the PI3K (phosphatidylinositol 3-kinase)
      Akt-mTOR (mammalian target of rapamycin) pathway was necessary and sufficient for
      the increase in p57Kip2, whereas MEK [mitogen-activated or extracellular signal
      regulated protein kinase (ERK) kinase]-ERK activity suppressed this increase,
      forming a regulatory circuit that limited proliferation in response to
      unaccompanied Akt activity. Knockdown of p57Kip2 enhanced the proliferative
      phenotype induced by tumor-associated PI3K mutant variants and released mammary
      epithelial acini from growth arrest during morphogenesis in three-dimensional
      culture. These results provide a potential explanation for the context-dependent
      proliferative activities of insulin and IGF-1 and for the finding that the CDKN1C
      locus encoding p57Kip2 is silenced in many breast cancers, which frequently show
      hyperactivation of the PI3K pathway. The status of p57Kip2 may thus be an
      important factor to assess when considering targeted therapy against the ERK or
      PI3K pathways.

PMID- 22394562
TI  - STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling
      pathway.
AB  - Cytosolic double-stranded DNA (dsDNA) stimulates the production of type I
      interferon (IFN) through the endoplasmic reticulum (ER)-resident adaptor protein
      STING (stimulator of IFN genes), which activates the transcription factor
      interferon regulatory factor 3 (IRF3); however, how STING activates IRF3 is
      unclear. Here, we showed that STING stimulates phosphorylation of IRF3 by the
      kinase TBK1 (TANK-binding kinase 1) in an in vitro reconstitution system. With
      this system, we identified a carboxyl-terminal region of STING that was both
      necessary and sufficient to activate TBK1 and stimulate the phosphorylation of
      IRF3. We also found that STING interacted with both TBK1 and IRF3 and that
      mutations in STING that selectively disrupted its binding to IRF3 abrogated
      phosphorylation of IRF3 without impairing the activation of TBK1. These results
      suggest that STING functions as a scaffold protein to specify and promote the
      phosphorylation of IRF3 by TBK1. This scaffolding function of STING (and possibly
      of other adaptor proteins) may explain why IRF3 is activated in only a subset of
      signaling pathways that activate TBK1.

PMID- 22394565
TI  - Retraction: Rapamycin-loaded nanoparticles for inhibition of neointimal
      hyperplasia in experimental vein grafts.

PMID- 22394563
TI  - In vitro antiprotozoal and cytotoxic activity of 33 ethonopharmacologically
      selected medicinal plants from Democratic Republic of Congo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The antiprotozoal and cytotoxic activity of the
      aqueous extracts from 33 medicinal plants, used by traditional healers for the
      treatment of various parasitic diseases and collected after an
      ethnopharmacological inventory conducted in the Bolongo area, Bandundu province
      in DR Congo, was evaluated. MATERIALS AND METHODS: Decoctions were prepared,
      lyophilized and evaluated for in vitro antiprotozoal activity against Trypanosoma
      b. brucei, Trypanosoma cruzi, Leishmania infantum, and the chloroquine- and
      pyrimethamine-resistant K1 strain of Plasmodium falciparum. Cytotoxicity against
      MRC-5 cells was included to assess selectivity of activity. RESULTS: Most of the
      tested extracts exhibited pronounced (IC(50)<=5MUg/ml) or good
      (5<IC(50)<=10MUg/ml) antiprotozoal activity against one or more of the selected
      protozoa. A total of 19 plant extracts inhibited Trypanosoma b. brucei,
      especially the extract from Isolona hexaloba stem bark (IC(50)=1.95MUg/ml,
      SI=16.5); 8 plant extracts were active against Trypanosoma cruzi, the extracts
      from Enanatia chlorantha stem bark and Quassia africana root bark being the most
      active with IC(50) values of 1.87 and 1.88MUg/ml, respectively (SI=3.0 and 3.3,
      respectively); 8 plant extracts showed activity against Leishmania infantum, with
      extracts from Napoleona vogelii stem bark and Quassia africana root bark as the
      most active with IC(50) values of 5.66 and 5.04MUg/ml (SI=11.3 and 1.2). Finally,
      9 plant extracts inhibited Plasmodium falciparum K1 with the extracts from
      Quassia africana (root bark and stem bark) being the most active ones with IC(50)
      values of 0.46 and 1.27MUg/ml (SI=13.7 and 13.6). Extracts from Enantia
      chlorantha stem bark, Piptadeniastrum africanum stem bark and Quassia africana
      root bark were cytotoxic for MRC-5 cells (CC(50)<10MUg/ml). CONCLUSIONS: These
      results can partly support and justify the traditional use of some of these plant
      species for the treatment of parasitic diseases.

PMID- 22394566
TI  - Dietary moderately oxidized oil induces expression of fibroblast growth factor 21
      in the liver of pigs.
AB  - BACKGROUND: Fibroblast growth factor 21 (FGF21), whose expression is induced by
      peroxisome proliferator-activated receptor alpha (PPARalpha), has been recently
      identified as a novel metabolic regulator which plays a crucial role in glucose
      homeostasis, lipid metabolism, insulin sensitivity and obesity. Previous studies
      have shown that administration of oxidized fats leads to an activation of
      PPARalpha in the liver. Therefore, the present study investigated the hypothesis
      that feeding of oxidized fats causes an induction of FGF21 in the liver. METHODS:
      Twenty four crossbred pigs were allocated to two groups of 12 pigs each and fed
      nutritionally adequate diets with either fresh rapeseed oil or oxidized rapeseed
      oil prepared by heating at a temperature of 175 degrees C for 72 h. RESULTS: In
      pigs fed the oxidized fat mRNA abundance and protein concentrations of FGF21 in
      liver were significantly increased (P < 0.05), and the protein concentrations of
      FGF21 in plasma tended to be increased (P < 0.1) in comparison to control pigs.
      Moreover, pigs fed the oxidized fat had increased transcript levels of the
      PPARalpha target genes acyl-CoA oxidase, carnitine palmitoyltransferase-1 and
      novel organic cation transporter 2 in the liver (P < 0.05), indicative of
      PPARalpha activation. CONCLUSION: The present study shows for the first time that
      administration of an oxidized fat induces the expression of FGF21 in the liver,
      probably mediated by activation of PPARalpha. Induction of FGF21 could be
      involved in several effects observed in animals administered an oxidized fat.

PMID- 22394567
TI  - Body mass index, surgery, and risk of venous thromboembolism in middle-aged
      women: a cohort study.
AB  - BACKGROUND: Obesity and surgery are known risk factors for venous thromboembolism
      (VTE), but there is limited information about the independent effects of obesity
      on the incidence of postoperative VTE. We linked questionnaire data from the
      Million Women Study with hospital admission and death records to examine the risk
      of VTE in relation to body mass index (BMI) both in the absence of surgery and in
      the first 12 weeks following an operation. METHODS AND RESULTS: Overall, 1 170
      495 women (mean age, 56.1 years) recruited in 1996 to 2001 through the National
      Health Service Breast Screening Programme in England and Scotland were followed
      for an average of 6 years, during which time 6438 were admitted to hospital or
      died of VTE. The adjusted relative risks of VTE increased progressively with
      increasing BMI and women with a BMI >= 35 kg/m(2) were 3-4 times as likely to
      develop VTE as those with a BMI 22.5 to 24.9 (relative risk 3.45 [95% CI 3.09
      3.86]). Overweight and obese women were more likely than lean women to be
      admitted for surgery and also to develop postoperative VTE. During a 12-week
      period without surgery, the incidence rates of VTE per 1000 women with a BMI < 25
      and >= 25 were 0.10 (0.09-0.10) and 0.19 (0.18-0.20); the corresponding rates in
      the 12 weeks following day and inpatient surgery were, respectively, about 4 and
      40 times higher. CONCLUSIONS: VTE risk increases with increasing BMI and the
      associated excess risk is much greater after surgery than without surgery.

PMID- 22394568
TI  - ST22 and ST239 MRSA duopoly in Singaporean hospitals: 2006-2010.
AB  - Surveillance is integral for the monitoring and control of infectious diseases.
      We conducted prospective laboratory surveillance of methicillin-resistant
      Staphylococcus aureus (MRSA) in five Singaporean public-sector hospitals from
      2006 to 2010, using WHONET 5.6 for data compilation and analysis. Molecular
      profiling using multilocus variable-number tandem-repeat analysis, staphylococcal
      cassette chromosome mec classification and multilocus sequence typing was
      performed for a random selection of isolates. Our results showed overall stable
      rates of infection and bacteraemia, although there was significant variance among
      the individual hospitals, with MRSA rates increasing in two smaller hospitals and
      showing a trend towards decreasing in the two largest hospitals. The proportion
      of blood isolates that are EMRSA-15 (ST22-IV) continued to increase over time,
      slowly replacing the multi-resistant ST239-III. A new MRSA clone - ST45-IV - is
      now responsible for a small subset of hospital infections locally. More effort is
      required in Singaporean hospitals in order to reduce the rates of MRSA infection
      significantly.

PMID- 22394569
TI  - Serum level of soluble CX3CL1/fractalkine is elevated in patients with
      polymyositis and dermatomyositis, which is correlated with disease activity.
AB  - INTRODUCTION: Polymyositis (PM) and dermatomyositis (DM) are chronic inflammatory
      muscle diseases, in which chemokines are thought to contribute to inflammatory
      cell migration into muscle. In this study, we retrospectively analyzed the
      expressions of CX3CL1/fractalkine and its corresponding receptor, CX3CR1, in
      muscle and lung with interstitial lung disease (ILD) of PM patients and DM
      patients, and determined the correlation between serum soluble CX3CL1 level and
      disease activity. METHODS: Expressions of CX3CL1 and CX3CR1 in muscle and lung
      tissue were analyzed by immunohistochemistry. Serum CX3CL1 concentrations were
      measured by ELISA. For evaluation of patients' disease activity, serum creatinine
      kinase, manual muscle testing, and the alveolar-arterial oxygen pressure
      difference were used independently. RESULTS: CX3CL1 was expressed on infiltrated
      mononuclear cells and endothelial cells in muscle affected by PM and DM and in
      lung with ILD, whereas CX3CR1 was expressed on some CD4+ T cells, a majority of
      CD8+ T cells, and most macrophages in muscle, and on infiltrated mononuclear
      cells in the lung. Serum soluble CX3CL1 was significantly higher in PM patients
      and DM patients than in healthy controls. The CX3CL1 level was correlated with
      serum creatinine kinase and manual muscle testing score. In patients with PM and
      DM with ILD, serum CX3CL1 was also correlated with alveolar-arterial oxygen
      pressure difference. Furthermore, CX3CL1 was significantly decreased after
      conventional treatment. CONCLUSIONS: The interaction between CX3CL1 and CX3CR1
      might contribute to the inflammatory cell infiltration into affected muscle and
      lung with ILD in PM patients and DM patients. Serum CX3CL1 level could be a
      surrogate marker of disease activity.

PMID- 22394570
TI  - A short online community readiness survey for smoke-free policy.
AB  - INTRODUCTION: Rural residents in the United States are more likely to use
      tobacco, have less access to tobacco control resources and efforts, and are more
      highly exposed to secondhand smoke than their urban counterparts. The purpose was
      to design and pilot test a shortened, self-administered online survey (Community
      Readiness Survey-Short form [CRS-S]) to assess community readiness for smoke-free
      policy in rural communities. The Community Readiness Survey-Long form (CRS-L) is
      a 30- to 90-min telephone-administered survey. The Community Readiness Model can
      guide the design of programs and policy interventions to reduce health risks.
      METHODS: 160 key informants from Wave 3 of a 5-year community-based randomized
      controlled trial set in Kentucky completed the CRS-L; 61 of approximately 140-284
      items were significantly related to the relevant readiness dimension subscores
      and selected for inclusion. The online CRS-S was created with these items using
      Qualtrics software; 43 smoke-free advocates who had completed the CRS-L during
      Wave 4 were invited to participate. Correlations between the CRS-S and the CRS-L
      on overall readiness and the dimension scores were calculated. Readiness scores
      were correlated with existence of public policy and voluntary smoke-free policies
      to assess convergent validity. RESULTS: The correlation between the overall CRS-S
      and CRS-L scores was relatively strong (.82), and there is evidence to support
      convergent validity. Most respondents completed the CRS-S in less than 15 min and
      preferred this format. CONCLUSIONS: The CRS-S is a valid and less time- and
      resource-intensive method to assess readiness for smoke-free policy in rural
      communities.

PMID- 22394571
TI  - Diffuser-aided diffuse optical imaging for breast tumor: a feasibility study
      based on time-resolved three-dimensional Monte Carlo modeling.
AB  - This study proposed diffuser-aided diffuse optical imaging (DADOI) as a new
      approach to improve the performance of the conventional diffuse optical
      tomography (DOT) approach for breast imaging. The 3-D breast model for Monte
      Carlo simulation is remodeled from clinical MRI image. The modified Beer
      Lambert's law is adopted with the DADOI approach to substitute the complex
      algorithms of inverse problem for mapping of spatial distribution, and the depth
      information is obtained based on the time-of-flight estimation. The simulation
      results demonstrate that the time-resolved Monte Carlo method can be capable of
      performing source-detector separations analysis. The dynamics of photon migration
      with various source-detector separations are analyzed for the characterization of
      breast tissue and estimation of optode arrangement. The source-detector
      separations should be less than 4 cm for breast imaging in DOT system. Meanwhile,
      the feasibility of DADOI was manifested in this study. In the results, DADOI
      approach can provide better imaging contrast and faster imaging than conventional
      DOT measurement. The DADOI approach possesses great potential to detect the
      breast tumor in early stage and chemotherapy monitoring that implies a good
      feasibility for clinical application.

PMID- 22394572
TI  - Limitations in the rapid extraction of evoked potentials using parametric
      modeling.
AB  - The rapid extraction of variations in evoked potentials (EPs) is of great
      clinical importance. Parametric modeling using autoregression with an exogenous
      input (ARX) and robust evoked potential estimator (REPE) are commonly used
      methods for extracting EPs over the conventional moving time average. However, a
      systematic study of the efficacy of these methods, using known synthetic EPs, has
      not been performed. Therefore, the current study evaluates the restrictions of
      these methods in the presence of known and systematic variations in EP component
      latency and signal-to-noise ratios (SNR). In the context of rapid extraction,
      variations of wave V of the auditory brainstem in response to stimulus intensity
      were considered. While the REPE methods were better able to recover the simulated
      model of the EP, morphology and the latency of the ARX-estimated EPs was a closer
      match to the actual EP than than that of the REPE-estimated EPs. We, therefore,
      concluded that ARX rapid extraction would perform better with regards to the
      rapid tracking of latency variations. By tracking simulated and empirically
      induced latency variations, we conclude that rapid EP extraction using ARX
      modeling is only capable of extracting latency variations of an EP in relatively
      high SNRs and, therefore, should be used with caution in low-noise environments.
      In particular, it is not a suitable method for the rapid extraction of early EP
      components such as the auditory brainstem potential.

PMID- 22394573
TI  - A state-space modeling approach for localization of focal current sources from
      MEG.
AB  - State-space modeling is a promising approach for current source reconstruction
      from magnetoencephalography (MEG) because it constrains the spatiotemporal
      behavior of inverse solutions in a flexible manner. However, state-space model
      based source localization research remains underdeveloped; extraction of
      spatially focal current sources and handling of the high dimensionality of the
      distributed source model remain problematic. In this study, we propose a novel
      state-space model-based method that resolves these problems, extending our
      previous source localization method to include a temporal constraint by state
      space modeling. To enable focal current reconstruction, we account for spatially
      inhomogeneous temporal dynamics by introducing dynamics model parameters that
      differ for each cortical position. The model parameters and the intensity of the
      current sources are jointly estimated according to a bayesian framework. We
      circumvent the high dimensionality of the problem by assuming prior distributions
      of the model parameters to reduce the sensitivity to unmodeled components, and by
      adopting variational bayesian inference to reduce the computational cost. Through
      simulation experiments and application to real MEG data, we have confirmed that
      our proposed method successfully reconstructs focal current activities, which
      evolve with their temporal dynamics.

PMID- 22394574
TI  - Rumination mediates the prospective effect of low self-esteem on depression: a
      five-wave longitudinal study.
AB  - Previous research supports the vulnerability model of low self-esteem and
      depression, which states that low self-esteem operates as a prospective risk
      factor for depression. However, it is unclear which processes mediate the effect
      of low self-esteem. To test for the mediating effect of rumination, the authors
      used longitudinal mediation models, which included exclusively prospective
      effects and controlled for autoregressive effects of the constructs. Data came
      from 663 individuals (aged 16 to 62 years), who were assessed 5 times over an 8
      month period. The results indicated that low self-esteem predicted subsequent
      rumination, which in turn predicted subsequent depression, and that rumination
      partially mediated the prospective effect of low self-esteem on depression. These
      findings held for both men and women, and for both affective-cognitive and
      somatic symptoms of depression. Future studies should test for the mediating
      effects of additional intrapersonal and interpersonal processes.

PMID- 22394575
TI  - Tilt-angle measurement of a sample stage using a capacitive liquid-based
      inclinometer.
AB  - Alignment of projection images in tomographic reconstruction is a critical
      process that governs the quality of the reconstructed three-dimensional (3D)
      image. The most popular alignment method is the marker-based alignment, which
      typically uses colloidal gold particles added to the specimen (called fiducial
      markers) to calculate the coordinates of each projection image in the tilt
      series. This method, however, is not effective when each image contains only a
      small number of fiducial markers. Therefore, of all the parameters required for
      alignment, we focussed on the tilt angle and attempted to gage it directly in
      order to examine whether the acquired angle is accurate enough to perform
      tomographic reconstruction. We showed that the tilt angle measured using a
      commercially available capacitive liquid-based inclinometer is more precise than
      the reading from the monitor of the electron microscope and that it can lead to
      3D reconstructions of quality similar to those obtained by the marker-based
      alignment method.

PMID- 22394576
TI  - Production of electron vortex beams carrying large orbital angular momentum using
      spiral zone plates.
AB  - We report the production of electron vortex beams carrying large orbital angular
      momentum (OAM) using micro-fabricated spiral zone plates. A series of the
      spherical waves, focussing onto different positions along the propagating
      direction of the electron beam, were observed. The nth order vortex beam has an
      OAM n times larger than that of the first-order vortex beam. We observed an
      electron vortex with an OAM up to   in a high-order diffracted wave. A linear
      dependence of the diameter of the vortex beam on the OAM was observed, being
      consistent to numerical simulations.

PMID- 22394577
TI  - Influence of pH, iron source, and Fe/ligand ratio on iron speciation in
      lignosulfonate complexes studied using Mossbauer spectroscopy. Implications on
      their fertilizer properties.
AB  - Iron chlorosis is a very common nutritional disorder in plants that can be
      treated using iron fertilizers. Synthetic chelates have been used to correct this
      problem, but nowadays environmental concerns have enforced the search for new,
      more environmentally friendly ligands, such as lignosulfonates. In this paper, Fe
      coordination environment and speciation in lignosulfonate (LS) complexes prepared
      under different experimental conditions were studied by (57)Fe Mossbauer
      spectroscopy in relation to the Fe-complexing capacities, chemical
      characteristics of the different products, and efficiency to provide iron in
      agronomic conditions. It has been observed that the complex formation between
      iron and lignosulfonates involves different coordination sites. When Fe(2+) is
      used to prepare the iron-LS product, complexes form weak adducts and are
      sensitive to oxidation, especially at neutral or alkaline pH. However, when
      Fe(3+) is used to form the complexes, both Fe(2+) and Fe(3+) are found. Reductive
      sugars, normally present in lignosulfonates, favor a relatively high content of
      Fe(2+) even in those complexes prepared using Fe(3+). The formation of amorphous
      ferrihydrite is also possible. With respect to the agronomical relevance of the
      Fe(2+)/Fe(3+) speciation provided by the Mossbauer spectra, it seems that the
      strong Fe(3+)-LS complexes are preferred when they are applied to the leaf,
      whereas root uptake in hydroponics could be more related with the presence of
      weak bonding sites.

PMID- 22394578
TI  - Towards modelling the vibrational signatures of functionalized surfaces:
      carboxylic acids on H-Si(111) surfaces.
AB  - In this work, we investigate the adsorption process of two carboxylic acids
      (stearic and undecylenic) on a H-Si(111) surface via the calculation of
      structural and energy changes as well as the simulation of their IR and Raman
      spectra. The two molecules adsorb differently at the surface since the stearic
      acid simply physisorbs while the undecylenic acid undergoes a chemical reaction
      with the hydrogen atoms of the surface. This difference is observed in the change
      of geometry during the adsorption. Indeed, the chemisorption of the undecylenic
      acid has a bigger impact on the structure than the physisorption of the stearic
      acid. Consistently, the former is also characterized by a larger value of
      adsorption energy and a smaller value of the tilting angle with respect to the
      normal plane. For both the IR and Raman signatures, the spectra of both molecules
      adsorbed at the surface are in a first approximation the superposition of the
      spectra of the Si cluster and of the carboxylic acid considered individually. The
      main deviation from this simple observation is the peak of the stretching Si-H
      (nu(Si-H)) mode, which is split into two peaks upon adsorption. As expected, the
      splitting is bigger for the chemisorption than the physisorption. The modes
      corresponding to atomic displacements close to the adsorption site display a
      frequency upshift by a dozen wavenumbers. One can also see the disappearance of
      the peaks associated with the C=C double bond when the undecylenic acid
      chemisorbs at the surface. The Raman and IR spectra are complementary and one can
      observe here that the most active Raman modes are generally IR inactive. Two
      exceptions to this are the two nu(Si-H) modes which are active in both
      spectroscopies. Finally, we compare our simulated spectra with some experimental
      measurements and we find an overall good agreement.

PMID- 22394579
TI  - Combining Tensor Space Analysis and Active Appearance Models for Aging Effect
      Simulation on Face Images.
AB  - Applications of the simulation of adult aging effects are widespread nowadays,
      whereas the difficulties in certain aspects restrict its development. In this
      paper, a method is proposed for simulating adult facial aging effects by means of
      super-resolution. Accounting for the nature of multimodalities in the face image
      set, multilinear algebra is introduced to represent and process the whole image
      set in tensor space. To ameliorate the aging simulation results generated by
      merely the super-resolution method, we further adopt active appearance models to
      reduce the blurring effects of the results through adding normalization of the
      faces and postprocessing to the algorithm. To evaluate our aging simulation
      method, the aged faces obtained are compared with the ground-truth face images of
      the same individuals and also assessed by several volunteers mainly from two
      perspectives: the aged faces' perceived age and their preservation effects of the
      original identities of subjects in the test images. Additionally, objective
      experiments based on an automatic age estimator and a face recognition method
      using eigenfaces are also conducted as another way of the evaluation. 

PMID- 22394580
TI  - Prediction of User's Web-Browsing Behavior: Application of Markov Model.
AB  - Web prediction is a classification problem in which we attempt to predict the
      next set of Web pages that a user may visit based on the knowledge of the
      previously visited pages. Predicting user's behavior while serving the Internet
      can be applied effectively in various critical applications. Such application has
      traditional tradeoffs between modeling complexity and prediction accuracy. In
      this paper, we analyze and study Markov model and all- Kth Markov model in Web
      prediction. We propose a new modified Markov model to alleviate the issue of
      scalability in the number of paths. In addition, we present a new two-tier
      prediction framework that creates an example classifier EC, based on the training
      examples and the generated classifiers. We show that such framework can improve
      the prediction time without compromising prediction accuracy. We have used
      standard benchmark data sets to analyze, compare, and demonstrate the
      effectiveness of our techniques using variations of Markov models and association
      rule mining. Our experiments show the effectiveness of our modified Markov model
      in reducing the number of paths without compromising accuracy. Additionally, the
      results support our analysis conclusions that accuracy improves with higher
      orders of all- Kth model. 

PMID- 22394581
TI  - Visual Control for Multirobot Organized Rendezvous.
AB  - This paper addresses the problem of visual control of a set of mobile robots. In
      our framework, the perception system consists of an uncalibrated flying camera
      performing an unknown general motion. The robots are assumed to undergo planar
      motion considering nonholonomic constraints. The goal of the control task is to
      drive the multirobot system to a desired rendezvous configuration relying solely
      on visual information given by the flying camera. The desired multirobot
      configuration is defined with an image of the set of robots in that configuration
      without any additional information. We propose a homography-based framework
      relying on the homography induced by the multirobot system that gives a desired
      homography to be used to define the reference target, and a new image-based
      control law that drives the robots to the desired configuration by imposing a
      rigidity constraint. This paper extends our previous work, and the main
      contributions are that the motion constraints on the flying camera are removed,
      the control law is improved by reducing the number of required steps, the
      stability of the new control law is proved, and real experiments are provided to
      validate the proposal. 

PMID- 22394582
TI  - Association analysis of photoperiodic flowering time genes in west and central
      African sorghum [Sorghum bicolor (L.) Moench].
AB  - BACKGROUND: Photoperiod-sensitive flowering is a key adaptive trait for sorghum
      (Sorghum bicolor) in West and Central Africa. In this study we performed an
      association analysis to investigate the effect of polymorphisms within the genes
      putatively related to variation in flowering time on photoperiod-sensitive
      flowering in sorghum. For this purpose a genetically characterized panel of 219
      sorghum accessions from West and Central Africa was evaluated for their
      photoperiod response index (PRI) based on two sowing dates under field
      conditions. RESULTS: Sorghum accessions used in our study were genotyped for
      single nucleotide polymorphisms (SNPs) in six genes putatively involved in the
      photoperiodic control of flowering time. Applying a mixed model approach and
      previously-determined population structure parameters to these candidate genes,
      we found significant associations between several SNPs with PRI for the genes
      CRYPTOCHROME 1 (CRY1-b1) and GIGANTEA (GI). CONCLUSIONS: The negative values of
      Tajima's D, found for the genes of our study, suggested that purifying selection
      has acted on genes involved in photoperiodic control of flowering time in
      sorghum. The SNP markers of our study that showed significant associations with
      PRI can be used to create functional markers to serve as important tools for
      marker-assisted selection of photoperiod-sensitive cultivars in sorghum.

PMID- 22394583
TI  - A biopsy simulation study to assess the accuracy of several transrectal
      ultrasonography (TRUS)-biopsy strategies compared with template prostate mapping
      biopsies in patients who have undergone radical prostatectomy.
AB  - What's known on the subject? and What does the study add? Transrectal
      ultrasonography (TRUS)-guided biopsies can miss prostate cancer and misclassify
      risk in a diagnostic setting; the exact extent to which it does so in a repeat
      biopsy strategy in men with low-intermediate risk prostate cancer is unknown. A
      simulation study of different biopsy strategies showed that repeat 12-core TRUS
      biopsy performs poorly. Adding anterior sampling improves on this but the highest
      accuracy is achieved using transperineal template prostate mapping using a 5 mm
      sampling frame. OBJECTIVE: To determine the effectiveness of two sampling
      strategies; repeat transrectal ultrasonography (TRUS)-biopsy and transperineal
      template prostate mapping (TPM) to detect and exclude lesions of >=0.2 mL or
      >=0.5 mL using computer simulation on reconstructed three-dimensional (3-D)
      computer models of radical whole-mount specimens. PATIENTS AND METHODS: Computer
      simulation on reconstructed 3-D computer models of radical whole-mount specimens
      was used to evaluate the performance characteristics of repeat TRUS-biopsy and
      TPM to detect and exclude lesions of >=0.2 mL or >=0.5 mL. In all, 107
      consecutive cases were analysed (1999-2001) with simulations repeated 500 times
      for each biopsy strategy. TPM and five different TRUS-biopsy strategies were
      simulated; the latter involved a standard 12-core sampling and incorporated
      variable amounts of error, as well as the addition of anterior cores.
      Sensitivity, specificity, negative and positive predictive values for detection
      of lesions with a volume of >=0.2 mL or >=0.5 mL were calculated. RESULTS: The
      mean (SD) age and PSA concentration were 61 (6.4) years and 8.5 (5.9) ng/mL,
      respectively.In all, 53% (57/107) had low-intermediate risk disease. In all, 665
      foci were reconstructed; there were 149 foci >=0.2 mL and 97 >= 0.5 mL in the
      full cohort and 68 >= 0.2 mL and 43 >= 0.5 mL in the low-intermediate risk group.
      Overall, TPM accuracy (area under the receiver operating curve, AUC) was ~0.90
      compared with AUC 0.70-0.80 for TRUS-biopsy. In addition, at best, TRUS-biopsy
      missed 30-40% of lesions of >=0.2 mL and >=0.5 mL whilst TPM missed 5% of such
      lesions. CONCLUSION: TPM under simulation conditions appears the most effective
      re-classification strategy, although augmented TRUS-biopsy techniques are better
      than standard TRUS-biopsy.

PMID- 22394585
TI  - Altered responsiveness to TGF-beta results in reduced Papss2 expression and
      alterations in the biomechanical properties of mouse articular cartilage.
AB  - INTRODUCTION: Previous studies have indicated that transforming growth factor
      beta (TGF-beta) signaling has a critical role in cartilage homeostasis and
      repair, yet the mechanisms of TGF-beta's chondroprotective effects are not known.
      Our objective in this study was to identify downstream targets of TGF-beta that
      could act to maintain biochemical and biomechanical properties of cartilage.
      METHODS: Tibial joints from 20-week-old mice that express a dominant-negative
      mutation of the TGF-beta type II receptor (DNIIR) were graded histologically for
      osteoarthritic changes and tested by indentation to evaluate their mechanical
      properties. To identify gene targets of TGF-beta, microarray analysis was
      performed using bovine articular chondrocytes grown in micromass culture that
      were either treated with TGF-beta or left untreated. Phosphoadenosine
      phosphosynthetase 2 (PAPSS2) was identified as a TGF-beta-responsive gene. Papss2
      expression is crucial for proper sulfation of cartilage matrix, and its
      deficiency causes skeletal defects in mice and humans that overlap with those
      seen in mice with mutations in TGF-beta-signaling genes. Regulation of Papss2 was
      verified by real time RT-PCR and Western blot analyses. Alterations in sulfation
      of glycosaminoglycans were analyzed by critical electrolyte concentration and
      Alcian blue staining and immunofluorescence for chondroitin-4-sulfate, unsulfated
      chondroitin and the aggrecan core protein. RESULTS: DNIIR mutants showed reduced
      mechanical properties and osteoarthritis-like changes when compared to wild-type
      control mice. Microarray analysis identified a group of genes encoding matrix
      modifying enzymes that were regulated by TGF-beta. Papss2 was upregulated in
      bovine articular chondrocytes after treatment with TGF-beta and downregulated in
      cartilage from DNIIR mice. Articular cartilage in DNIIR mice demonstrated reduced
      Alcian blue staining at critical electrolyte concentrations and reduced
      chondroitin-4-sulfate staining. Staining for unsulfated chondroitin sulfate was
      increased, whereas staining for the aggrecan core protein was comparable in DNIIR
      and wild-type mice. CONCLUSION: TGF-beta maintains biomechanical properties and
      regulates expression of Papss2 and sulfation of glycosaminoglycans in mouse
      articular cartilage.

PMID- 22394586
TI  - Aortic arch thrombectomy in a 2.8 kilogram neonate--a case report and review of
      the literature.
AB  - Aortic arch thrombus is a rare occurrence in neonates. In the few described
      cases, this has mainly been associated with sepsis or early postnatal
      interventions, such as insertion of umbilical arterial line. We describe a case
      of occlusive aortic arch thrombus in a neonate who presented with signs of
      critical coarctation and successfully underwent surgical thrombectomy on deep
      hypothermic circulatory arrest. We also present a review of the most recently
      published cases of aortic arch thrombus in neonates and the treatment options
      employed.

PMID- 22394587
TI  - Efficacy of an absorbable polyglycolic acid patch in surgery for pneumothorax due
      to silicosis.
AB  - BACKGROUND: We conducted a retrospective study to evaluate the efficacy and
      safety of an absorbable polyglycolic acid (PGA) patch in surgery for refractory
      pneumothorax due to silicosis. METHODS: A retrospective analysis was performed of
      56 patients who received thoracotomy or thoracoscopic surgery for refractory
      pneumothorax due to silicosis between 1995 and 2010. An absorbable PGA patch was
      used as a reinforcement or repair material after resection of the bulla in 24
      operations and it was not used in another 32 operations. Clinical outcomes were
      compared between the two groups (with a PGA and without a PGA). RESULTS: We found
      that the duration of postoperative chest drainage (5.04+/-1.12 days vs. 8.19+/
      1.60 days, p<0.01) and hospital stay after the operation (8.33+/-1.34 days vs.
      11.56+/-1.50 days, p<0.01) were significantly shorter in patients who used an
      absorbable PGA patch in the operation compared with those who did not use a PGA
      patch. The incidence of initial air leakage (58.3% [14/24] vs. 93.8% [30/32],
      p<0.05) and relapse rate of pneumothorax in 6 months (4% [1/24] vs. 25% [8/32],
      p<0.05) were also significantly lower in patients who used an absorbable PGA
      patch in the operation compared with those who did not use a PGA patch. No
      related adverse effects of the absorbable PGA patch occurred after the
      operations. CONCLUSIONS: Use of an absorbable PGA patch as a reinforcement or
      repair material in surgery for refractory pneumothorax due to silicosis can
      reduce postoperative air leakage and improve clinical outcome.

PMID- 22394588
TI  - Sublingual apomorphine as a neuroendocrine probe.
AB  - Subcutaneous apomorphine, a dopaminergic agonist, is used as a neuroendocrine
      probe for assessing central dopaminergic activity. The aim of our study was to
      test sublingual apomorphine for the same purpose. We administered sublingual
      apomorphine in a weight-dependent dose (0.033 mg/kg) to 42 healthy men. Prolactin
      and growth hormone levels were measured before and after the administration at
      15, 30, 45, 60, 75, 90, 120, 150 and 180 min. Subjects filled in Zung's self
      assessment scores of anxiety (SAS) and depression (SDS) questionnaires before and
      after the test. Areas under the curve for prolactin and growth hormone levels
      were calculated using the trapezoidal rule. All subjects showed decreased
      prolactin, and 40/42 subjects showed increased growth hormone, in response to
      sublingual apomorphine. Average peak value for prolactin was -4.6+/-1.8 MUg/l.
      Average peak value for growth hormone was 8.1+/-8.5 ng/ml for the whole group,
      and 9.6+/-8.1 ng/ml after exclusion of two negative growth hormone responders.
      Sublingual apomorphine produced no major side effects. Significant decreases in
      SAS (21.5+/-5.7 vs. 20.6+/-5.5) and SDS (9.7+/-7.8 vs. 7.8+/-6.8) scores were
      observed after the test. Sublingually administered apomorphine appears to be well
      tolerated and useful as a neuroendocrine marker of central dopaminergic activity.

PMID- 22394589
TI  - Effects of mineral content on the fracture properties of equine cortical bone in
      double-notched beams.
AB  - We recently developed a method to measure cortical bone fracture initiation
      toughness using a double-notched beam in four-point bending. This method was used
      to test the hypothesis that mineralization around the two notch roots is
      correlated with fracture toughness and crack extension (physical damage). Total
      energy absorbed to failure negatively correlated with average mineralization of
      the beam (r(2)=0.62), but not with notch root mineralization. Fracture initiation
      toughness was positively correlated to mineralization at the broken notch root
      (r(2)=0.34). Crack length extension at the unbroken notch was strongly negatively
      correlated with the average mineralization of the notch roots (r(2)=0.81) whereas
      crack length extension at the broken notch did not correlate with any of the
      mineralization measurements. Mineralization at the notch roots and the average
      mineralization contributed independently to the mechanical and damage properties.
      The data are consistent with a hypothesis that a) high notch root mineralization
      results in less stable crack length extension but high force to initiate unstable
      crack propagation while b) higher average mineralization leads to low post-yield
      (and total) energy absorption to failure.

PMID- 22394590
TI  - Histamine release and surface CD200R1 staining as sensitive methods for assessing
      murine mast cell activation.
AB  - Mast cells are important effector cells of allergy and are involved in the
      pathology of many other diseases. Measurement of beta-hexosaminidase activity,
      the most commonly used method for evaluation of murine mast cell activity,
      requires a large number of cells and thus is of limited utility for studying mast
      cells in mouse models of disease. In this study we evaluated the sensitivity of
      histamine release as compared to beta-hexosaminidase activity in the measurement
      of mast cell activation. Whereas a minimum of 6*10(4) mast cells per ml were
      required to detect slight increases in beta-hexosaminidase activity after anti
      IgE and ionomycin stimulation, substantial increases in histamine release could
      be detected under the same activating conditions with as few as 480 mast cells
      per ml. These findings demonstrate that measurement of histamine release is
      substantially more sensitive than assessment of beta-hexosaminidase activity for
      detecting mast cell activation. Additionally, we describe a novel flow cytometric
      method for detecting murine mast cell activation. When using 7.5*10(5) peritoneal
      cells per condition and gating on IgE+c-kit+cells, mast cell expression of
      surface CD200R1 increased after both IgE and non IgE-mediated activation. This
      flow cytometric procedure was uncomplicated and rapid, with increases in surface
      CD200R1 expression appearing after as little as 30 min of stimulation time.
      Measuring histamine release and surface CD200R1 expression are sensitive
      approaches for detection of murine mast cell activation. Further, both approaches
      can be done on unpurified peritoneal cell populations. By requiring low numbers
      of cells, these approaches are ideal for investigating mast cell activation in
      murine models of disease.

PMID- 22394591
TI  - Radiation and cancer risk in atomic-bomb survivors.
AB  - With the aim of accurately assessing the effects of radiation exposure in the
      Japanese atomic-bomb survivors, the Radiation Effects Research Foundation has,
      over several decades, conducted studies of the Life Span Study (LSS) cohort,
      comprising 93 000 atomic-bomb survivors and 27 000 controls. Solid cancer: the
      recent report on solid cancer incidence found that at age 70 years following
      exposure at age 30 years, solid cancer rates increase by about 35%  Gy(-1) for
      men and 58% Gy(-1)  for women. Age-at-exposure is an important risk modifier. In
      the case of lung cancer, cigarette smoking has been found to be an important risk
      modifier. Radiation has similar effects on first-primary and second-primary
      cancer risks. Finally, radiation-associated increases in cancer rates appear to
      persist throughout life. Leukaemia: the recent report on leukaemia mortality
      suggests that radiation effects on leukaemia mortality persisted for more than 50
      years. Moreover, significant dose-response for myelodysplastic syndrome was
      observed in Nagasaki LSS members even 40-60 years after radiation exposure.
      Future perspective: given the continuing solid cancer increase in the survivor
      population, the LSS will likely continue to provide important new information on
      radiation exposure and solid cancer risks for another 15-20 years, especially for
      those exposed at a young age.

PMID- 22394593
TI  - International expert symposium in Fukushima, September 2011.

PMID- 22394592
TI  - Effect of zeolite (clinoptilolite) as feed additive in Tunisian broilers on the
      total flora, meat texture and the production of omega 3 polyunsaturated fatty
      acid.
AB  - BACKGROUND: Increasing consumer demand for healthier food products has led to the
      development of governmental policies regarding health claims in many developed
      countries. In this context, contamination of poultry by food-borne pathogens is
      considered one of the major problems facing the progress of the poultry industry
      in Tunisia. RESULT: Zeolite (Clinoptilolites) was added to chicken feed at
      concentrations 0,5% or 1% and was evaluated for its effectiveness to reduce total
      flora in chickens and its effects on performance of the production. The broilers
      were given free and continuous access to a nutritionally non-limiting diet (in
      meal form)that was either a basal diet or a' zeolite diet' (the basal diet
      supplemented with clinoptilolite at a level of 0,5% or 1%). It was found that
      adding zeolite in the broiler diet significantly (p < 0,05) reduced total flora
      levels, as compared to the control, on the chicken body. In addition, it was
      found that zeolite treatment had a positive effect on performance production and
      organoleptic parameters that were measured and mainly on the increase level of
      Omega 3 fatty acid. CONCLUSION: This study showed the significance of using
      zeolite, as a feed additive for broilers, as part of a comprehensive program to
      control total flora at the broiler farm and to increase level of Omega 3 fatty
      acid on the chicken body.

PMID- 22394594
TI  - Clinical evaluation of a novel bipolar radiofrequency ablation system for renal
      masses.
AB  - What's known on the subject? and What does the study add? With the advancement of
      minimally invasive surgery, the management of small renal masses (SRM) has
      dramatically changed. Ablative technology such as radiofrequency ablation (RFA)
      and cryoablation have emerged as viable alternative modalities to extirpative
      surgery. RFA is one of the most studied and applied energy-based, needle-ablative
      treatment modalities, with encouraging mid- and long-term oncological outcomes.
      Monopolar devices have several shortcomings. The electrodes are susceptible to
      the cooling effect of nearby blood vessels that act as a 'heat sink', limiting
      the extent of tissue ablation and forming lesions with asymmetric borders and
      'skip lesions'. Therefore, it is difficult to monitor and accurately predict the
      size of ablated lesions. A novel bipolar radiofrequency ablation (BRFA) device
      has been recently developed to address concerns with monopolar systems (Trod
      Medical, Paris, France). The BRFA system addresses the limitations of monopolar
      RFA, in terms of lesion size, targeting, consistency and concerns about cell
      death in the ablated area. We evaluated the BRFA device in 10 patients undergoing
      laparoscopic partial or radical nephrectomy. The present study demonstrates the
      safety and efficacy of a novel BRFA device. A BRFA device can produce a defined
      reproducible lesion with a precise transition zone to normal tissue. The area of
      ablated tissue exhibited completely devitalized cells and precise transition
      zone. With these characteristics, the potential advantages of this new technology
      during RFA ablation of SRM include less collateral damage and more complete
      ablation without skip lesions. This has the potential to lower rates of local
      recurrence and reduce incidence of skin burns. Further follow-up studies are
      necessary to determine its oncological efficacy. OBJECTIVE: To evaluate a novel
      bipolar radiofrequency ablation (BRFA) system for the destruction of kidney
      tumours in patients. MATERIALS AND METHODS: Bipolar radiofrequency ablation
      (BRFA) was used to ablate renal masses in 10 patients undergoing laparoscopic
      radical or partial nephrectomy. The probe was placed percutaneously and
      laparoscopically guided into the tumour after routine laparoscopic exposure. The
      electrical current was continuously adjusted by the generator to overcome
      disruption from increasing impedance created from desiccated tissue. The
      specimens were then excised in routine fashion and analysed by a single
      pathologist. Lesion size and shape, and size of the transition zone to viable
      tissue were measured via nicotinamide adenine dinucleotide (NADH) staining.
      RESULTS: Ablation was successful in all 10 tumours. Mean time to set up and place
      the probe was between 2 and 4 min. Duration of ablation was 200 s. None of the
      ablated tissue showed signs of viable cells by histological examination and NADH
      staining. The mean size of the ablation zone was 6.26 cm(3), with regular borders
      and a tapered cylindrical shape similar to the shape of the outer coil. The width
      of the transition zone, or area spanning complete tissue ablation to the first
      viable cells, ranged from 10 to 60 um. There were no complications noted due to
      the ablation. CONCLUSIONS: A BRFA device can produce a defined reproducible
      lesion with a precise transition zone to normal tissue. The area of ablated
      tissue exhibited completely devitalized cells and precise transition zone.

PMID- 22394595
TI  - Socioeconomic status and tobacco consumption among adolescents: a multilevel
      analysis of Argentina's Global Youth Tobacco Survey.
AB  - INTRODUCTION: The relationship between poverty and tobacco consumption among
      adolescents has not been extensively studied, and what evidence exists has come
      almost entirely from developed countries. Moreover, the impact of contextual
      factors--such as school-level poverty--remains unclear. METHODS: We obtained
      information about smoking behavior from the Global Youth Tobacco Survey in
      Argentina in 2007. School-level characteristics were derived by matching schools
      to census areas from the 2001 Census. Additional school-level information was
      obtained from the Ministry of Education. Random intercept models were used to
      evaluate the associations of school-level variables (poverty in the census area
      of the school, school receipt of social assistance, and public or private status)
      with current smoking, intention to quit, secondhand smoke exposure outside the
      home, support for smoke-free laws, purchase of single cigarettes among smokers,
      and susceptibility to smoking in 5 years among nonsmokers. RESULTS: After
      controlling for age and sex, students attending schools receiving social
      assistance were more likely to smoke (odds ratio [OR] 1.35, 95% CI 1.02-1.80) and
      to purchase loose cigarettes (OR 1.66, 95% CI 1.08-2.54), whereas school poverty
      was significantly associated with secondhand smoke exposure (OR 1.27, 95% CI 1.04
      1.58). CONCLUSION: This study shows that an association exists between
      unfavorable contextual school characteristics and tobacco consumption and related
      measures among youth in Argentina. Efforts to prevent smoking may need to address
      the school-level factors that place youth at higher risk.

PMID- 22394596
TI  - Identification of an active, well-tolerated dose of pralatrexate in patients with
      relapsed or refractory cutaneous T-cell lymphoma.
AB  - Systemic treatment for cutaneous T-cell lymphoma (CTCL) involves the use of less
      aggressive, well-tolerated therapies. Pralatrexate is a novel antifolate with
      high affinity for reduced folate carrier-1. A dose de-escalation strategy
      identified recommended pralatrexate dosing for patients with CTCL that
      demonstrated high activity, good rates of disease control, and an acceptable
      toxicity profile for continuous long-term dosing. Eligibility included mycosis
      fungoides, Sezary syndrome, or primary cutaneous anaplastic large cell lymphoma,
      with disease progression after >= 1 prior systemic therapy. The starting dose and
      schedule was 30 mg/m(2)/wk intravenously for 3 of 4 (3/4) weeks. Subsequent
      starting doses were 20, 15, and 10 mg/m(2)/wk for 3/4 or 2 of 3 (2/3) weeks.
      Response was evaluated by the modified severity-weighted adjustment tool. Fifty
      four patients were treated. The recommended regimen was identified as 15
      mg/m(2)/wk for 3/4 weeks and was explored in the expansion cohort. In 29 patients
      treated overall with the recommended dosing regimen, the median number of prior
      systemic therapies was 4. Pralatrexate was administered for a median of 4 cycles;
      response rate was 45%. The most common grade 3 adverse event (AE) was mucositis
      (17%); the only grade 4 AE was leukopenia (3%). Pralatrexate 15 mg/m(2)/wk for
      3/4 weeks shows high activity with acceptable toxicity in patients with
      relapsed/refractory CTCL.

PMID- 22394597
TI  - PF4/heparin-antibody complex induces monocyte tissue factor expression and
      release of tissue factor positive microparticles by activation of FcgammaRI.
AB  - Heparin-induced thrombocytopenia (HIT) is a potentially devastating form of drug
      induced thrombocytopenia that occurs in patients receiving heparin for prevention
      or treatment of thrombosis. Patients with HIT develop autoantibodies to the
      platelet factor 4 (PF4)/heparin complex, which is termed the HIT Ab complex.
      Despite a decrease in the platelet count, the most feared complication of HIT is
      thrombosis. The mechanism of thrombosis in HIT remains poorly understood. We
      investigated the effects of the HIT Ab complex on tissue factor (TF) expression
      and release of TF-positive microparticles in peripheral blood mononuclear cells
      and monocytes. To model these effects ex vivo, we used a murine mAb specific for
      the PF4/heparin complex (KKO), as well as plasma from patients with HIT. We found
      that the HIT Ab complex induced TF expression in monocytes and the release of TF
      positive microparticles. Further, we found that induction of TF is mediated via
      engagement of the FcgammaRI receptor and activation of the MEK1-ERK1/2 signaling
      pathway. Our data suggest that monocyte TF may contribute to the development of
      thrombosis in patients with HIT.

PMID- 22394598
TI  - ALK+ALCLs induce cutaneous, HMGB-1-dependent IL-8/CXCL8 production by
      keratinocytes through NF-kappaB activation.
AB  - Anaplastic large-cell lymphomas (ALCLs) bearing the t(2;5) translocation
      (ALK(+)ALCLs) are frequently characterized by skin colonization and associated
      with a poor prognosis. Using conditional transgenic models of anaplastic lymphoma
      kinase-positive (ALK(+)) lymphomas and human ALK(+)ALCL cell lines, in the
      present study, we show that high-mobility-group box-1 (HMGB-1), a proinflammatory
      cytokine, is released by ALK(+) cells, and demonstrate extracellular HMGB-1
      stimulated secretion of the IL-8 chemokine by HaCaT keratinocytes through the
      involvement of MMP-9, PAR-2, and the NF-kappaB pathway. Furthermore, we
      demonstrate that, in vitro, IL-8 is able to induce the invasiveness of ALK(+)
      cells, which express the IL-8 receptors CXCR1 and CXCR2. In vitro and in vivo,
      HMGB-1 inhibition achieved by glycyrrhizin treatment led to a drastic reduction
      in ALK(+) cell invasiveness. The pathophysiological relevance of our observations
      was confirmed by demonstrating that the HMGB-1 and IL-8 receptors are expressed
      in ALK(+)ALCL biopsies. We have also shown that IL-8 secretion is correlated with
      leukemic dissemination of ALK(+) cells in a significant number of patients. The
      results of the present study demonstrate for the first time a relationship among
      the pro-inflammatory mediators HMGB-1, MMP-9, PAR-2, and IL-8. We propose that
      these mediators create a premetastatic niche within the skin, thereby
      participating in ALK(+) lymphoma epidermotropism.

PMID- 22394599
TI  - CD4+ T-cell epitopes associated with antibody responses after intravenously and
      subcutaneously applied human FVIII in humanized hemophilic E17 HLA-DRB1*1501
      mice.
AB  - Today it is generally accepted that B cells require cognate interactions with
      CD4(+) T cells to develop high-affinity antibodies against proteins. CD4(+) T
      cells recognize peptides (epitopes) presented by MHC class II molecules that are
      expressed on antigen-presenting cells. Structural features of both the MHC class
      II molecule and the peptide determine the specificity of CD4(+) T cells that can
      bind to the MHC class II-peptide complex. We used a new humanized hemophilic
      mouse model to identify FVIII peptides presented by HLA-DRB1*1501. This model
      carries a knockout of all murine MHC class II molecules and expresses a chimeric
      murine-human MHC class II complex that contains the peptide-binding sites of the
      human HLA-DRB1*1501. When mice were treated with human FVIII, the proportion of
      mice that developed antibodies depended on the application route of FVIII and the
      activation state of the innate immune system. We identified 8 FVIII peptide
      regions that contained CD4(+) T-cell epitopes presented by HLA-DRB1*1501 to
      CD4(+) T cells during immune responses against FVIII. CD4(+) T-cell responses
      after intravenous and subcutaneous application of FVIII involved the same
      immunodominant FVIII epitopes. Interestingly, most of the 8 peptide regions
      contained promiscuous epitopes that bound to several different HLA-DR proteins in
      in vitro binding assays.

PMID- 22394600
TI  - Hypoxia promotes dissemination of multiple myeloma through acquisition of
      epithelial to mesenchymal transition-like features.
AB  - The spread of multiple myeloma (MM) involves (re)circulation into the peripheral
      blood and (re)entrance or homing of MM cells into new sites of the BM. Hypoxia in
      solid tumors was shown to promote metastasis through activation of proteins
      involved in the epithelial-mesenchymal transition (EMT) process. We hypothesized
      that MM-associated hypoxic conditions activate EMT-related proteins and promote
      metastasis of MM cells. In the present study, we have shown that hypoxia
      activates EMT-related machinery in MM cells, decreases the expression of E
      cadherin, and, consequently, decreases the adhesion of MM cells to the BM and
      enhances egress of MM cells to the circulation. In parallel, hypoxia increased
      the expression of CXCR4, consequently increasing the migration and homing of
      circulating MM cells to new BM niches. Further studies to manipulate hypoxia to
      regulate tumor dissemination as a therapeutic strategy are warranted.

PMID- 22394601
TI  - Risk categories and refractory CLL in the era of chemoimmunotherapy.
AB  - Standardized criteria for diagnosis and response evaluation in chronic
      lymphocytic leukemia (CLL) are essential to achieve comparability of results and
      improvement of clinical care. With the increasing range of therapeutic options,
      the treatment context is important when defining refractory CLL. Refractory CLL
      has been defined as no response or response lasting <= 6 months from last
      therapy. This subgroup has a very poor outcome, and many trials use this group as
      an entry point for early drug development. With the intensification of first-line
      regimens, the proportion of patients with refractory CLL using these criteria
      decreases. This has immediate consequences for recruitment of patients into
      trials as well as salvage strategies. Conversely, patients who are not refractory
      according to the traditional definition but who have suboptimal or short response
      to intense therapy also have a very poor outcome. In this Perspective, we discuss
      recent results that may lead to a reassessment of risk categories in CLL focusing
      on fit patients who are eligible for all treatment options. We cover aspects of
      the history and biologic basis for refractory CLL and will focus on how emerging
      data on treatment failure from large trials using chemoimmunotherapy may help to
      define risk groups in CLL.

PMID- 22394602
TI  - Clinical significance of antibodies to Ro52/TRIM21 in systemic sclerosis.
AB  - INTRODUCTION: Autoantibodies to Ro52 recently identified as TRIM21 are among the
      most common autoantibodies in systemic autoimmune rheumatic diseases, but their
      clinical association remains poorly understood. We undertook this study to
      determine the clinical and serologic associations of anti-Ro52/TRIM21 antibodies
      in patients with systemic sclerosis (SSc). METHODS: Detailed clinical data and
      sera from 963 patients with SSc enrolled in a multicenter cohort study were
      collected and entered into a central database. Antibodies to Ro52/TRIM21 and
      other autoantibodies were detected with an addressable laser-bead immunoassay and
      different enzyme-linked immunosorbent assay (ELISA) systems. Associations between
      anti-Ro52/TRIM21 antibodies and clinical and other serologic manifestations of
      SSc were investigated. RESULTS: Anti-Ro52/TRIM21 antibodies were present in 20%
      of SSc patients and overlapped with other main SSc-related antibodies, including
      anti-centromere (by immunofluorescence and centromere protein (CENP)-A and CENP-B
      ELISA), anti-topoisomerase I, anti-RNA polymerase III, and anti-Pm/Scl
      antibodies. Anti-Ro52/TRIM21 antibodies were strongly associated with
      interstitial lung disease (odds ratio (OR), 1.53; 95% confidence interval (CI),
      1.11 to 2.12; P = 0.0091) and overlap syndrome (OR, 2.06; 95% CI, 1.01 to 4.19; P
      = 0.0059). CONCLUSIONS: Anti-Ro52/TRIM21 antibodies were the second most common
      autoantibodies in this SSc cohort. In SSc, anti-Ro52/TRIM21 antibodies may be a
      marker of interstitial lung disease and overlap syndrome.

PMID- 22394603
TI  - An exploration of the experiences and perspectives of New Zealanders with fetal
      alcohol spectrum disorder.
AB  - BACKGROUND: The experiences and perspectives of New Zealanders with fetal alcohol
      spectrum disorder (FASD) need to be heard since no research to date has been
      performed. FASD, a neuro-developmental disability with life-lasting effects, is
      irreversible. The condition is caused by prenatal exposure to alcohol.
      OBJECTIVES: This study aimed to explore and understand the daily challenges of
      New Zealand individuals with FASD. METHODS: Our sequential mixed methods design
      used two discrete but compatible qualitative methodologies--transcendental
      phenomenology in Phase One and classic grounded theory in Phase Two--framed by
      the meta-theory of pragmatism, which allows the use of 'what works' in research.
      One methodology alone would not have answered our research question. Using the
      same sample of 14 individuals, 14 to 37 years, two separate data sets were
      produced sequentially using face-to-face unstructured interviews. Participants
      had been diagnosed with either fetal alcohol syndrome (FAS) or fetal alcohol
      effects (FAE). Data credibility was checked using triangulation. RESULTS: Six
      themes common to the participants' experiences emerged: daily challenges in the
      classroom; daily challenges in the workplace; coping with mental health issues;
      memory problems; socialization difficulties and involvement with the law and
      authority. Phase Two's emerging theory revealed that because the participants
      perceived they had been under-supported by the social/health systems, many
      engaged in illegal behaviours (secondary disabilities) and experienced employment
      and social problems. Many disavowed having the disability, but with maturity and
      knowing the signs and symptoms, accepted it. They suggested ways in which their
      concerns could be resolved. CONCLUSION: In order that progress in this field can
      take place, health and social agencies, educational and criminal justice systems
      and policy-makers need to have increased awareness of the disability and the
      complex problems that individuals with the disability and their families face.

PMID- 22394604
TI  - Acute onset of intracranial subdural hemorrhage five days after spinal anesthesia
      for knee arthroscopic surgery: a case report.
AB  - INTRODUCTION: Spinal anesthesia is a widely used general purpose anesthesia.
      However, serious complications, such as intracranial subdural hemorrhage, can
      rarely occur. CASE PRESENTATION: We report the case of a 73-year-old Japanese
      woman who had acute onset of intracranial subdural hemorrhage five days after
      spinal anesthesia for knee arthroscopic surgery. CONCLUSION: This case highlights
      the need to pay attention to acute intracranial subdural hemorrhage as a
      complication after spinal anesthesia. If the headache persists even in a supine
      position or nausea occurs abruptly, computed tomography or magnetic resonance
      imaging of the brain should be conducted. An intracranial subdural hematoma may
      have a serious outcome and is an important differential diagnosis for headache
      after spinal anesthesia.

PMID- 22394605
TI  - Inhibition of hepatic uptake transporters by flavonoids.
AB  - Members of the human SLC superfamily such as organic anion transporting
      polypeptide 1B1 (OATP1B1), OATP1B3, and organic cation transporter 1 (OCT1) are
      drug uptake transporters that are localised on the basolateral membrane of
      hepatocytes mediating the uptake of drugs such as atorvastatin and metformin into
      hepatocytes. Ingredients of food such as flavonoids influence the effects of
      drugs, e.g. by inhibition of drug transporters. Therefore, we investigated the
      impact of the Ginkgo biloba flavonoids apigenin, kaempferol, and quercetin, and
      the grapefruit flavonoids naringenin, naringin, and rutin on the OATP1B1,
      OATP1B3, and OCT1 transport activity. Transporter expressing HEK293 cell lines
      were used with [3H]sulfobromophthalein ([3H]BSP) as substrate for OATP1B1 and
      OATP1B3, [3H]atorvastatin as substrate for OATP1B1, and [3H]1-methyl-4
      phenylpyridinium ([3H]MPP(+)) as substrate for OCT1. The G. biloba flavonoids
      showed a competitive inhibition of the OATP1B1- and OATP1B3-mediated [3H]BSP and
      the OATP1B1-mediated [3H]atorvastatin uptake. Quercetin was the most potent
      inhibitor of the OATP1B1- and OATP1B3-mediated [3H]BSP transport with K(i)-values
      of 8.8+/-0.8MUM and 7.8+/-1.7MUM, respectively. For the inhibition of the OATP1B1
      mediated [3H]atorvastatin transport, apigenin was the most potent inhibitor with
      a K(i) value of 0.6+/-0.2MUM. Among the grapefruit flavonoids, naringenin was the
      most potent inhibitor of the OATP1B1- and OATP1B3-mediated [3H]BSP transport with
      IC(50)-values of 81.6+/-1.1MUM and 101.1+/-1.1MUM, respectively. All investigated
      flavonoids showed no significant inhibition of the OCT1-mediated [3H]MPP(+)
      uptake. Taken together, these in vitro studies showed that the investigated
      flavonoids inhibit the OATP1B1- and OATP1B3-mediated drug transport, which could
      be a mechanism for food-drug interactions in humans.

PMID- 22394607
TI  - Hierarchical organization of cortical morphology of decision-making when
      deconstructing Iowa Gambling Task performance in healthy adults.
AB  - The Iowa Gambling Task (IGT) is a measure of decision-making, in which
      alternative metrics have greater construct validity than conventional metrics. No
      large scale study has examined the neural correlates in healthy adults. We
      administered the IGT and structural MRI to 124 healthy participants. We analyzed
      the conventional IGT metric of advantageous minus disadvantageous choices (i.e.,
      decks C + D minus decks A + B), and three alternative metrics based on choices
      from decks D and A alone, and all selections from each deck. Using regression and
      voxel-based morphometry, we examined regional gray matter volumes as predictors
      of IGT performance. No neural correlates of the conventional metric emerged, and
      the neural correlates of individual deck selections were disparate from one
      another. Alternative metrics showed expected neural correlates of decision-making
      in prefrontal cortex, insula, thalamus, and other regions. IGT alternative
      metrics have neural correlates consistent with decision-making theory as those
      difference scores reduce heterogeneity in cognitive processes. The CD-AB metric
      construct failure may reflect an artificial amalgamation of processes. The D-A
      metric appears to more successfully combine multiple levels of representation
      (dorsolateral prefrontal cortex, sub-cortical, cerebellar).

PMID- 22394606
TI  - Clinical characteristics and patterns of healthcare utilization in patients with
      painful neuropathic disorders in UK general practice: a retrospective cohort
      study.
AB  - BACKGROUND: Clinical characteristics and patterns of healthcare utilization in
      patients with painful neuropathic disorders (PNDs) who are under the care of
      general practitioners (GPs) in the UK are not well understood. METHODS: Using a
      large electronic UK database, we identified all adults (age >= 18 years) with any
      GP encounters between 1 January 2006-31 December 2006 at which a diagnosis of PND
      was noted ("PND patients"). An age-and gender-matched comparison group also was
      constituted consisting of randomly selected patients with one or more GP
      encounters-but no mention of PNDs-during this period. Characteristics and
      patterns of healthcare utilization of patients in the two groups were then
      examined over the one-year study period. RESULTS: The study sample consisted of
      31,688 patients with mention of PNDs and an equal number of matched comparators;
      mean age was 56 years, and 62% were women. The prevalence of various
      comorbidities was higher among patients in the PND group, including digestive
      disorders (31% vs. 17% for comparison group), circulatory disorders (29% vs.
      22%), and depression (4% vs. 3%) (all p < 0.01). Receipt of prescriptions for
      pain-related pharmacotherapy also was higher among PND patients, including
      nonsteroidal anti-inflammatory drugs (56% of PND patients had one or more such
      prescriptions vs. only 22% in the comparison group), opioids (49% vs. 12%),
      tricyclic antidepressants (20% vs. 1%), and antiepileptics (12% vs. 1%) (all p <
      0.01). PND patients also averaged significantly more GP visits (22.8 vs. 14.2)
      and referrals to specialists (2.8 vs. 1.4) over one year (both comparisons p <
      0.01). CONCLUSIONS: Patients with PNDs under the care of GPs in the UK have
      relatively high levels of use of healthcare services and pain-related
      pharmacotherapy.

PMID- 22394608
TI  - Impact of age on clinicopathological outcomes and recurrence-free survival after
      the surgical management of nonseminomatous germ cell tumour.
AB  - Study Type - Therapy (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? The effect of advancing age on the
      clinicopathological outcomes of men with germ cell testicular cancers remains
      uncertain. Through the review and comparison of the present large cohort of men
      with testis cancer, we report on our experience in men aged >=50 years. Our
      results showed similar clinical and pathological characteristics, and survival
      outcomes that compare favourably with those of men aged <50 years. OBJECTIVE: To
      determine the impact of age on clinicopathological findings and disease
      recurrence in men with nonseminomatous germ cell tumour (NSGCT) undergoing
      retroperitoneal lymph node dissection (RPLND). PATIENTS AND METHODS: We
      identified 1246 patients with NSGCT who underwent either primary or post
      chemotherapy-RPLND (PC-RPLND) between 1989 and 2006 from our prospective testis
      cancer database. * Perioperative characteristics were compared among men aged <
      or >=50 years. * Multivariable models were used to evaluate the association of
      age with disease-free survival, controlling for established clinical and
      pathological features. RESULTS: Of 514 men undergoing primary and 732 men
      undergoing PC-RPLND, 12 (2.3%) and 23 (3.1%) were aged >=50 years, respectively.
      * There were no significant differences between men aged < or >=50 years for
      perioperative clinicopathological characteristics, with the exception of pre
      RPLND CT nodal size. * The pathological distributions at primary RPLND were
      similar in men aged < or >=50 years. After PC-RPLND, there were no differences in
      RPLND histology, number of lymph nodes resected, estimated blood loss, hospital
      stay, or perioperative complication rate. * Age at surgery was not a significant
      predictor of disease recurrence when subjected to a multivariable analysis.
      CONCLUSIONS: Our data suggests that age at RPLND does not predict for disease
      recurrence and men aged >=50 years had similar pre- and postoperative
      characteristics to those aged <50 years. * We conclude that RPLND can be safely
      performed in men aged >=50 years and these patients should be offered optimal
      treatment regimens for NSGCT as directed according to established guidelines.

PMID- 22394609
TI  - Aquaporin-4 autoantibodies cause asymptomatic aquaporin-4 loss and activate
      astrocytes in mouse.
AB  - BACKGROUND: Neuromyelitis optica (NMO) is a central nervous system inflammatory
      demyelinating disorder. Up to 90% of patients are seropositive for aquaporin-4
      autoantibodies (AQP4 Ab). The pathogenetic mechanisms underlying clinical onset
      and relapse of NMO are uncertain. OBJECTIVE: Study the pathogenicity of AQP4 Ab
      in the absence of complement activation. METHODS: Female C57BL/6N mice (human IgG
      cannot activate mouse complements) pretreated with complete Freund's adjuvant
      (CFA, day 0) and pertussis toxin (PTx, day 0 and day 2) were transferred with IgG
      isolated from serum of healthy subjects or NMO patients (AQP4 Ab-positive or
      negative) intraperitoneally (day 7-9). Mice were observed for signs of
      experimental autoimmune encephalomyelitis (EAE) by standard 6-grade EAE scores.
      Spinal cord was obtained at day 11 for immunohistochemistry. RESULTS: None of the
      mice had clinical signs of encephalomyelitis, inflammatory cells infiltration or
      demyelination of spinal cord. CFA and PTx induce BBB breakdown evidenced by
      leakage of human IgG into cord parenchyma. Patchy areas of AQP4 loss were
      observed in spinal cord of mice transferred with IgG from AQP4 Ab-positive NMO
      patients but not in mice transferred with IgG from AQP4 Ab-negative NMO patients
      or healthy subjects; but there was no loss of glial fibrillary acidic protein
      immunoreactivity in all mice. Markedly increased proliferation of astrocytic
      processes suggestive of astrocytic activation was observed in mice transferred
      with IgG from AQP4 Ab-positive patients. CONCLUSION: AQP4 Ab cause asymptomatic
      AQP4 loss and astrocytic activation but not myelitis, demyelination or astrocytic
      cytotoxicity in spinal cord of mouse in the absence of complement activation.

PMID- 22394610
TI  - Lessons from Chernobyl and prognosis for Fukushima: radiological consequences.
AB  - The following are considered: results of large-scale radiation epidemiological
      studies of the health effects of the Chernobyl accident, radiation risks for
      emergency workers and the affected population; and verification of ICRP risk
      models taking into account data on the Chernobyl accident and preliminary
      prognostic estimates of potential radiological consequences of the Fukushima
      disaster.

PMID- 22394611
TI  - Neonatal testosterone partially organizes sex differences in stress-induced
      emotionality in mice.
AB  - Major depressive disorder (MDD) is a debilitating disorder of altered mood
      regulation. Despite well established sex differences in MDD prevalence, the
      mechanism underlying the increased female vulnerability remains unknown. Although
      evidence suggests an influence of adult circulating hormone levels on mood (i.e.
      activational effects of hormones), MDD prevalence is consistently higher in women
      across life stages (and therefore hormonal states), suggesting that additional
      underlying structural or biological differences place women at higher risk.
      Studies in human subjects and in rodent models suggest a developmental origin for
      mood disorders, and interestingly, a developmental process also establishes sex
      differences in the brain. Hence, based on these parallel developmental
      trajectories, we hypothesized that a proportion of the female higher
      vulnerability to MDD may originate from the differential organization of mood
      regulatory neural networks early in life (i.e. organizational effects of
      hormones). To test this hypothesis in a rodent system, we took advantage of a
      well-established technique used in the field of sexual differentiation (neonatal
      injection with testosterone) to masculinize sexually dimorphic brain regions in
      female mice. We then investigated adult behavioral consequences relating to
      emotionality by comparing neonatal testosterone-treated females to normal males
      and females. Under baseline/trait conditions, neonatal testosterone treatment of
      female mice did not influence adult emotionality, but masculinized adult
      locomotor activity, as revealed by the activational actions of hormones.
      Conversely, the increased vulnerability of female mice to develop high
      emotionality following unpredictable chronic mild stress (UCMS) was partially
      masculinized by neonatal testosterone exposure, with no effect on post-UCMS
      locomotion. The elevated female UCMS-induced vulnerability did not differ between
      adult hormone treated groups. These results demonstrate that sex differences in
      adult emotionality in mice are partially caused by the organizational effects of
      sex hormones during development, hence supporting a developmental hypothesis of
      the human adult female prevalence of MDD.

PMID- 22394612
TI  - Comparison of oncological outcomes after segmental ureterectomy or radical
      nephroureterectomy in urothelial carcinomas of the upper urinary tract: results
      from a large French multicentre study.
AB  - What's known on the subject? and What does the study add? Upper urinary tract
      urothelial carcinomas (UUT-UCs) are rare tumours. Because of the aggressive
      pattern of UC, radical nephroureterectomy (RNU) with bladder cuff removal remains
      the 'gold-standard' treatment. However, conservative strategies, such as
      segmental ureterectomy (SU) or endourological management, have also been
      developed in patients with imperative indications. Some teams are now advocating
      the use of conservative management more commonly in cases of elective indications
      of UUT-UCs. Due to the paucity of cases of UUT-UC, only limited data are
      available on the oncological outcomes afforded by conservative management. We
      retrospectively investigated the oncological outcomes after SU and RNU in a large
      multi-institutional database. Overall, 52 patients were treated with SU and 416
      with RNU. There was no statistical difference between the RNU and SU groups for
      the 5-year probability of cancer-specific survival, recurrence-free survival and
      metastasis-free survival. The type of surgery was not a significant prognostic
      factor in univariate analysis. The results were the same in a subgroup analysis
      of only unifocal tumours of the distal ureter with a diameter of <2 cm and of low
      stage (<=T2). Our results suggest that oncological outcomes after conservative
      treatment with SU are comparable to RNU for the management of UUT-UC in select
      cases. OBJECTIVE: To compare recurrence-free survival (RFS), metastasis-free
      survival (MFS) and cancer-specific survival (CSS) after segmental ureterectomy
      (SU) vs radical nephroureterectomy (RNU) for urothelial carcinoma (UC) of the
      upper urinary tract (UUT-UC) located in the ureter. PATIENTS AND METHODS: We
      performed a multi-institutional retrospective review of patients with UUT-UC who
      had undergone RNU or SU between 1995 and 2010. Type of surgery, Tumour-Node
      Metastasis status, tumour grade, lymphovascular invasion and positive surgical
      margin were tested as prognostic factors for survival. RESULTS: In all, 52
      patients were treated with SU and 416 with RNU. The median (range) follow-up was
      26 (10-48) months. The 5-year probability of CSS, RFS and MFS for SU and RNU were
      87.9% and 86.3%, respectively (P = 0.99); 37% and 47.9%, respectively (P = 0.48);
      81.9% and 85.4%, respectively (P = 0.51). In univariable analysis, type of
      surgery (SU vs RNU) failed to affect CSS, RFS and MFS (P = 0.94, 0.42 and 0.53,
      respectively). In multivariable analyses, pT stage and pN stage achieved
      independent predictor status for CSS (P = 0.005 and 0.007, respectively); the
      positive surgical margin and pT stage were independent prognostic factors of RFS
      and MFS (P = 0.001, 0.04, 0.009 and 0.001, respectively). The main limitation of
      the study is its retrospective design, which is due to the rarity of the disease.
      CONCLUSIONS: Short-term oncological outcomes after conservative treatment with SU
      are comparable to RNU for the management of UUT-UC in select cases and should be
      considered an option. In every other case, RNU still represents the 'gold
      standard' for the treatment of UUT-UC.

PMID- 22394613
TI  - International expert symposium in Fukushima: radiation and health risks.

PMID- 22394615
TI  - Neuroprotection for ischaemic stroke: translation from the bench to the bedside.
AB  - Neuroprotection seeks to restrict injury to the brain parenchyma following an
      ischaemic insult by preventing salvageable neurons from dying. The concept of
      neuroprotection has shown promise in experimental studies, but has failed to
      translate into clinical success. Many reasons exist for this including the
      heterogeneity of human stroke and the lack of methodological agreement between
      preclinical and clinical studies. Even with the proposed Stroke Therapy Academic
      Industry Roundtable criteria for preclinical development of neuroprotective
      agents for stroke, we have still seen limited success in the clinic, an example
      being NXY-059, which fulfilled nearly all the Stroke Therapy Academic Industry
      Roundtable criteria. There are currently a number of ongoing trials for
      neuroprotective strategies including hypothermia and albumin, but the outcome of
      these approaches remains to be seen. Combination therapies with thrombolysis also
      need to be fully investigated, as restoration of oxygen and glucose will always
      be the best therapy to protect against cell death from stroke. There are also a
      number of promising neuroprotectants in preclinical development including
      haematopoietic growth factors, and inhibitors of the nicotinamide adenine
      dinucleotide phosphate oxidases, a source of free radical production which is a
      key step in the pathophysiology of acute ischaemic stroke. For these
      neuroprotectants to succeed, essential quality standards need to be adhered to;
      however, these must remain realistic as the evidence that standardization of
      procedures improves translational success remains absent for stroke.

PMID- 22394616
TI  - Low-volume filling of microplate wells using vibration.
AB  - Smaller fluid samples can offer higher sensitivity under analysis and allow more
      samples from a sparse specimen. However, for a microplate well there is a minimum
      volume requirement arising from the need for the fluid/air interface to make
      contact only on the walls of the well, a condition which allows high-quality
      undistorted optical imaging due to the minimum curvature of this interface. In
      this work, mechanical vibration is investigated as a method to significantly
      decrease this minimum volume requirement. Furthermore, low-frequency excitation
      is shown to be ideal for handling multiple wells (such as in a microplate)
      simultaneously.

PMID- 22394614
TI  - Cell cycle arrest is not yet senescence, which is not just cell cycle arrest:
      terminology for TOR-driven aging.
AB  - Cell cycle arrest is not yet senescence. When the cell cycle is arrested, an
      inappropriate growth-promotion converts an arrest into senescence
      (geroconversion). By inhibiting the growth-promoting mTOR pathway, rapamycin
      decelerates geroconversion of the arrested cells. And as a striking example,
      while causing arrest, p53 may decelerate or suppress geroconversion (in some
      conditions). Here I discuss the meaning of geroconversion and also the terms
      gerogenes, gerossuppressors, gerosuppressants, gerogenic pathways, gero
      promoters, hyperfunction and feedback resistance, regenerative potential,
      hypertrophy and secondary atrophy, pro-gerogenic and gerogenic cells.

PMID- 22394617
TI  - Engineering resonance energy transfer for advanced immunoassays: the case of
      celiac disease.
AB  - Celiac disease (CD) is an immune-mediated disorder affecting genetically
      predisposed subjects. It is caused by the ingestion of wheat gluten and related
      prolamins. A final diagnosis for this disease can be obtained by examination of
      jejunal biopsies. Nevertheless, different analytical approaches have been
      established to detect the presence of anti-tissue transglutaminase antibodies
      that represent a serological hallmark of the disease. In this work, we explored a
      new method for the diagnosis of CD based on the detection of serum anti
      transglutaminase antibodies by resonance energy transfer (RET) between donor
      molecules and acceptor molecules. In particular, we labeled the liver
      transglutaminase (tTG) enzyme from guinea pig and the rabbit anti-tTG antibodies
      with a couple of fluorescence probes that are able to make RET if they are
      located within with Forster distance. We labeled tTG with the fluorescence probe
      DyLight 594 as donor and the anti-tTG antibodies with the fluorescence probe
      DyLight 649 as acceptor. However, due to the large size of the formed complex
      (tTG/anti-tTG), and consequently to the low efficiency energy transfer process
      between the donor-acceptor molecules, we explored a new experimental approach
      that allows us to extend the utilizable range of RET between donor:acceptor pairs
      by using one single molecule as donor and multiple molecules as energy acceptors,
      instead of using a single acceptor molecule as usually occurs in RET experiments.
      The obtained results clearly show that the use of one donor and multiacceptor
      strategy enables for a simple and rapid detection of serum anti-transglutaminase
      antibodies. In addition, our results point out that it is possible to consider
      this approach as a new method for a wide variety of analytical assays.

PMID- 22394618
TI  - Gender, perceived competence and the enjoyment of physical education in children:
      a longitudinal examination.
AB  - BACKGROUND: The current study examined associations between gender, perceived
      athletic competence, and enjoyment of physical education (PE) class over time in
      a cohort of children enrolled in grade four (ages 9 or 10) at baseline (n =
      2262). METHODS: We assessed each student 5 times over a period of 2 years. We
      used mixed effects modeling to examine change over time in enjoyment of PE.
      RESULTS: Enjoyment of PE declined among girls but remained constant among boys.
      Higher levels of perceived competence were associated with higher PE enjoyment. A
      3-way interaction between gender, competence, and time revealed that PE enjoyment
      was lowest and declined most markedly among girls with low perceived athletic
      competence. Among boys with low competence, enjoyment remained at a consistently
      low level. CONCLUSIONS: Our results indicate that lower perceived athletic
      competence is associated with low enjoyment of PE, and, among girls, with
      declining enjoyment. Findings suggest that interventions in a PE context that
      target perceived competence should be considered in future work.

PMID- 22394619
TI  - Lhermitte-Duclos disease presenting with positron emission tomography-magnetic
      resonance fusion imaging: a case report.
AB  - INTRODUCTION: Lhermitte-Duclos disease or dysplastic gangliocytoma of the
      cerebellum is an extremely rare tumor. It is a slowly enlarging mass within the
      cerebellar cortex. The majority of cases are diagnosed in the third or fourth
      decade of life. CASE PRESENTATION: We report the case of a 37-year-old Caucasian
      woman who underwent positron emission tomography-computed tomography with
      fluorine-18-fluorodeoxyglucose for evaluation of a solitary lung node. No
      pathological uptake was detected in the solitary lung node but the positron
      emission tomography-computed tomography of her brain showed intense tracer
      uptake, suggestive of a malignant neoplasm, in a mass in her left cerebellar
      lobe. Our patient had experienced two years of occipital headache and movement
      disorder. Subsequently, magnetic resonance imaging was performed with contrast
      agent administration, showing a large subtentorial mass in her left cerebellar
      hemisphere, with compression and dislocation of the fourth ventricle. Metabolic
      data provided by positron emission tomography and morphological magnetic
      resonance imaging views were fused in post-processing, allowing a diagnosis of
      dysplastic gangliocytoma with increased glucose metabolism. Total resection of
      the tumor was performed and histological examination confirmed the diagnosis of
      Lhermitte-Duclos disease. CONCLUSIONS: Our case indicates that increased uptake
      of fluorine-18-fluorodeoxyglucose may be misinterpreted as a neoplastic process
      in the evaluation of patients with Lhermitte-Duclos disease, but supports the
      usefulness of integrated positron emission tomography-magnetic resonance imaging
      in the exact pathophysiologic explanation of this disease and in making the
      correct diagnosis. However, an accurate physical examination and exact knowledge
      of clinical data is of the utmost importance.

PMID- 22394621
TI  - Advances in understanding gray matter pathology in multiple sclerosis: are we
      ready to redefine disease pathogenesis?
AB  - The purpose of this special issue in BMC Neurology is to summarize advances in
      our understanding of the pathological, immunological, imaging and clinical
      concepts of gray matter (GM) pathology in patients with multiple sclerosis (MS).
      Review articles by Lucchinetti and Popescu, Walker and colleagues, Hulst and
      colleagues and Horakova and colleagues summarize important recent advances in
      understanding GM damage and its implications to MS pathogenesis. They also raise
      a number of important new questions and outline comprehensive approaches to
      addressing those questions in years to come. In the last decade, the use of
      immunohistochemistry staining methods and more advanced imaging techniques to
      detect GM lesions, like double inversion recovery, contributed to a surge of
      studies related to cortical and subcortical GM pathology in MS. It is becoming
      more apparent from recent biopsy studies that subpial cortical lesions in early
      MS are highly inflammatory. The mechanisms responsible for triggering meningeal
      inflammation in MS patients are not yet elucidated, and they should be further
      investigated in relation to their role in initiating and perpetuating the disease
      process. Determining the role of antigens, environmental and genetic factors in
      the pathogenesis of GM involvement in MS is critical. The early involvement of
      cortical and subcortical GM damage in MS is very intriguing and needs to be
      further studied. As established in numerous cross-sectional and longitudinal
      studies, GM damage is a better predictor of physical disability and cognitive
      impairment than WM damage. Monitoring the evolution of GM damage is becoming an
      important marker in predicting future disease course and response to therapy in
      MS patients.

PMID- 22394620
TI  - Rat tail static compression model mimics extracellular matrix metabolic
      imbalances of matrix metalloproteinases, aggrecanases, and tissue inhibitors of
      metalloproteinases in intervertebral disc degeneration.
AB  - INTRODUCTION: The longitudinal degradation mechanism of extracellular matrix
      (ECM) in the interbertebral disc remains unclear. Our objective was to elucidate
      catabolic and anabolic gene expression profiles and their balances in
      intervertebral disc degeneration using a static compression model. METHODS: Forty
      eight 12-week-old male Sprague-Dawley rat tails were instrumented with an
      Ilizarov-type device with springs and loaded statically at 1.3 MPa for up to 56
      days. Experimental loaded and distal-unloaded control discs were harvested and
      analyzed by real-time reverse transcription-polymerase chain reaction (PCR)
      messenger RNA quantification for catabolic genes [matrix metalloproteinase (MMP)
      1a, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, a disintegrin and metalloproteinase with
      thrombospondin motifs (ADAMTS)-4, and ADAMTS-5], anti-catabolic genes [tissue
      inhibitor of metalloproteinases (TIMP)-1, TIMP-2, and TIMP-3], ECM genes
      [aggrecan-1, collagen type 1-alpha1, and collagen type 2-alpha1], and pro
      inflammatory cytokine genes [tumor necrosis factor (TNF)-alpha, interleukin (IL)
      1alpha, IL-1beta, and IL-6]. Immunohistochemistry for MMP-3, ADAMTS-4, ADAMTS-5,
      TIMP-1, TIMP-2, and TIMP-3 was performed to assess their protein expression level
      and distribution. The presence of MMP- and aggrecanase-cleaved aggrecan
      neoepitopes was similarly investigated to evaluate aggrecanolytic activity.
      RESULTS: Quantitative PCR demonstrated up-regulation of all MMPs and ADAMTS-4 but
      not ADAMTS-5. TIMP-1 and TIMP-2 were almost unchanged while TIMP-3 was down
      regulated. Down-regulation of aggrecan-1 and collagen type 2-alpha1 and up
      regulation of collagen type 1-alpha1 were observed. Despite TNF-alpha elevation,
      ILs developed little to no up-regulation. Immunohistochemistry showed, in the
      nucleus pulposus, the percentage of immunopositive cells of MMP-cleaved aggrecan
      neoepitope increased from 7 through 56 days with increased MMP-3 and decreased
      TIMP-1 and TIMP-2 immunopositivity. The percentage of immunopositive cells of
      aggrecanase-cleaved aggrecan neoepitope increased at 7 and 28 days only with
      decreased TIMP-3 immunopositivity. In the annulus fibrosus, MMP-cleaved aggrecan
      neoepitope presented much the same expression pattern. Aggrecanase-cleaved
      aggrecan neoepitope increased at 7 and 28 days only with increased ADAMTS-4 and
      ADAMTS-5 immunopositivity. CONCLUSIONS: This rat tail sustained static
      compression model mimics ECM metabolic imbalances of MMPs, aggrecanases, and
      TIMPs in human degenerative discs. A dominant imbalance of MMP-3/TIMP-1 and TIMP
      2 relative to ADAMTS-4 and ADAMTS-5/TIMP-3 signifies an advanced stage of
      intervertebral disc degeneration.

PMID- 22394623
TI  - The Chernobyl experience in the area of retrospective dosimetry.
AB  - The Chernobyl accident, which occurred on 26 April 1986 at a nuclear power plant
      located less than 150 km north of Kiev, was the largest nuclear accident to date.
      The unprecedented scale of the accident was determined not only by the amount of
      released activity, but also by the number of workers and of the general public
      involved, and therefore exposed to increased doses of ionising radiation. Due to
      the unexpected and large scale of the accident, dosimetry techniques and
      practices were far from the optimum; personal dosimetry of cleanup workers
      (liquidators) was not complete, and there were no direct measurements of the
      exposures of members of the public. As a result, an acute need for retrospective
      dose assessment was dictated by radiation protection and research considerations.
      In response, substantial efforts have been made to reconstruct doses for the main
      exposed cohorts, using a broad variety of newly developed methods: analytical,
      biological and physical (electron paramagnetic resonance spectroscopy of teeth,
      thermoluminescence of quartz) and modelling. This paper reviews the extensive
      experience gained by the National Research Center for Radiation Medicine, Academy
      of Medical Sciences, Ukraine in the field of retrospective dosimetry of large
      cohorts of exposed population and professionals. These dose reconstruction
      projects were implemented, in particular, in the framework of epidemiological
      studies, designed to follow-up the medical consequences of the Chernobyl accident
      and study health effects of ionizing radiation, particularly Ukrainian-American
      studies of cataracts and leukaemia among liquidators.

PMID- 22394622
TI  - Potential for inhalation exposure to engineered nanoparticles from nanotechnology
      based cosmetic powders.
AB  - BACKGROUND: The market of nanotechnology-based consumer products is rapidly
      expanding, and the lack of scientific evidence describing the accompanying
      exposure and health risks stalls the discussion regarding its guidance and
      regulation. OBJECTIVES: We investigated the potential for human contact and
      inhalation exposure to nanomaterials when using nanotechnology-based cosmetic
      powders and compare them with analogous products not marketed as nanotechnology
      based. METHODS: We characterized the products using transmission electron
      microscopy (TEM) and laser diffraction spectroscopy and found nanoparticles in
      five of six tested products. TEM photomicrographs showed highly agglomerated
      states of nanoparticles in the products. We realistically simulated the use of
      cosmetic powders by applying them to the face of a human mannequin head while
      simultaneously sampling the released airborne particles through the ports
      installed in the mannequin's nostrils. RESULTS: We found that a user would be
      exposed to nanomaterial predominantly through nanoparticle-containing
      agglomerates larger than the 1-100-nm aerosol fraction. CONCLUSIONS: Predominant
      deposition of nanomaterial(s) will occur in the tracheobronchial and head airways
      -not in the alveolar region as would be expected based on the size of primary
      nanoparticles. This could potentially lead to different health effects than
      expected based on the current understanding of nanoparticle behavior and
      toxicology studies for the alveolar region.

PMID- 22394624
TI  - Activation of CaMKII as a key regulator of reactive oxygen species production in
      diabetic rat heart.
AB  - Diabetes mellitus is a risk factor for heart failure. Increased reactive oxygen
      species (ROS) have been proposed as a possible mechanism of cardiac dysfunction
      in diabetic patients. However, the mechanisms of ROS increase are still elusive.
      We hypothesized that activation of Ca(2+)/calmodulin-dependent protein kinase II
      (CaMKII) induced by impaired intracellular Ca(2+) ([Ca(2+)](i)) metabolism may
      stimulate ROS production in the diabetic heart. Cultured cardiomyocytes from
      neonatal rats were exposed to high glucose concentrations (25 mmol/L) and ROS
      levels were analyzed in 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein
      diacetate, acetyl ester (CM-H(2)DCFDA)-loaded cells by flow cytometry analysis.
      Exposure to high glucose concentrations for 24h significantly increased CM
      H(2)DCFDA fluorescence, which was significantly inhibited by 1,2-bis (o
      aminophenoxy) ethane- N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (BAPTA
      AM), a [Ca(2+)](i) chelator, and KB-R7943, an inhibitor of the Na(+)-Ca(2+)
      exchanger (NCX) in the reverse mode. These results indicate that [Ca(2+)](i)
      increase by NCX activation may induce ROS increase following exposure to high
      glucose concentrations. We confirmed that exposure to high glucose concentrations
      significantly increased [Ca(2+)](i), which was inhibited by KB-R7943. Na(+)-H(+)
      exchanger (NHE) is a key factor in [Ca(2+)](i) metabolism, and is known to
      activate NCX by increasing the intracellular Na(+) ([Na(+)](i)) level. We showed
      that the expression of NHE isoform 1 and NHE activity increased following
      exposure to high glucose concentrations by evaluating protein expressions and
      intracellular pH recovery from acid loading. Exposure to high glucose
      concentrations up-regulated phosphorylated CaMKII expression in cardiomyocytes
      that was inhibited by KB-R7943. Further, autocamtide 2-related inhibitory peptide
      (AIP), a CaMKII inhibitor, significantly attenuated the ROS increase following
      exposure to high glucose concentrations. We confirmed these results obtained in
      in vitro experiments in an animal model of diabetes. ROS level and components of
      NADPH oxidase, p47phox and p67phox were up-regulated in streptozotocin-induced
      diabetic rat heart, which were attenuated by KN-93, a CaMKII inhibitor.
      Consistently, expression of phosphorylated CaMKII was increased in the diabetic
      heart. Activation of CaMKII by impaired [Ca(2+)](i) metabolism may be a mechanism
      of ROS increase in the heart with diabetes mellitus.

PMID- 22394625
TI  - Carbohydrate restriction and lactate transporter inhibition in a mouse xenograft
      model of human prostate cancer.
AB  - What's known on the subject? and What does the study add? It is known that both
      lactate inhibition and carbohydrate restriction inhibit tumour growth. What is
      unknown is whether the two work synergistically together. This study adds that
      though the combination of lactate inhibition and carbohydrate restriction did not
      synergistically slow tumour growth in our model, we confirmed that carbohydrate
      restriction started after tumour inoculation slowed tumour growth. Moreover,
      lactate inhibition resulted in changes in the tumour microenvironment that may
      have implications for future metabolic targeting of prostate cancer growth.
      OBJECTIVE: To determine if a no-carbohydrate ketogenic diet (NCKD) and lactate
      transporter inhibition can exert a synergistic effect on delaying prostate tumour
      growth in a xenograft mouse model of human prostate cancer. MATERIALS AND
      METHODS: 120 nude athymic male mice (aged 6-8 weeks) were injected s.c. in the
      flank with 1.0 * 10(5) LAPC-4 prostate cancer cells. * Mice were randomized to
      one of four treatment groups: Western diet (WD, 35% fat, 16% protein, 49%
      carbohydrate) and vehicle (Veh) treatment; WD and mono-carboxylate transporter-1
      (MCT1) inhibition via alpha-cyano-4-hydroxycinnamate (CHC) delivered through a
      mini osmotic pump; NCKD (84% fat, 16% protein, 0% carbohydrate) plus Veh; or NCKD
      and MCT1 inhibition. * Mice were fed and weighed three times per week and feed
      was adjusted to maintain similar body weights. * Tumour size was measured twice
      weekly and the combined effect of treatment was tested via Kruskal-Wallis
      analysis of all four groups. Independent effects of treatment (NCKD vs WD and CHC
      vs Veh) on tumour volume were tested using linear regression analysis. * All mice
      were killed on Day 53 (conclusion of pump ejection), and serum and tumour
      sections were analysed for various markers. Again, combined and independent
      effects of treatment were tested using Kruskal-Wallis and linear regression
      analysis, respectively. RESULTS: There were no significant differences in tumour
      volumes among the four groups (P= 0.09). * When testing the independent effects
      of treatment, NCKD was significantly associated with lower tumour volumes at the
      end of the experiment (P= 0.026), while CHC administration was not (P= 0.981).
      However, CHC was associated with increased necrotic fraction (P < 0.001).
      CONCLUSIONS: Differences in tumour volumes were observed only in comparisons
      between mice fed a NCKD and mice fed a WD. * MCT1 inhibition did not have a
      significant effect on tumour volume, although it was associated with increased
      necrotic fraction.

PMID- 22394626
TI  - [Effects of high magneto-gravitational environment on calcium/calmodulin signal
      of MG63 osteoblast-like cells].
AB  - AIM: To investigate the effects of high magneto-gravitational environment on
      Ca(2+);]/calmodulin (CaM) signal of MG63 osteoblast-like cells. METHODS: A
      special designed large gradient high magnetic field could produce three different
      high magneto-gravitational environments including MUg (12 T),  1 g (16 T) and 2 g
      (12 T). The effects of high magneto-gravitational environments on intracellular
      free Ca(2+);] concentration ([Ca(2+);](i);) and protein expression including
      calmodulin (CaM),  myosin light chain kinases (MLCK) and phosphorylated
      Ca(2+);]/CaM dependent protein kinase II(pCaMKII) were measured by Fluo-3/AM or
      Western blot,  respectively. RESULTS: When compared with control group,  an
      increase of [Ca(2+);](i); of MG63 was caused by strong magnetic field;   Compared
      to 2 g,  MUg decreased [Ca(2+);](i); of MG63. The protein expression of CaM and
      pCaMKIIof MG63 cells was decreased by simulated weightlessness. CONCLUSION:
      [Ca(2+);](i); of MG63 cells was increased by strong magnetic field;   simulated
      weightlessness inhibited Ca(2+);/CaM signaling of MG63 cells.

PMID- 22394627
TI  - [Study on combined immunization of rAd/MDC-VP1 and pcDNA3/MDC-VP1 against 
      Coxsackievirus B3 challenge in mice].
AB  - AIM: To immunize the mice using the rAd/MDC-VP1 prime-pcDNA3/MDC-VP1 boost
      strategy and observe its immunological effect against Coxsackievirus B3(CVB3).
      METHODS: BALB/c mice were randomly divided into four groups:  PBS group, rAd/MDC
      VP1 group,  pcDNA3/MDC-VP1 group and rAd/MDC-VP1 prime-pcDNA3/MDC-VP1 boost
      group. Mice in each group were immunized intramuscularly. The titers of serum IgG
      and neutralizing antibody were tested by ELISA and trace neutralization assays
      respectively. The Lymphocytes proliferation activity and specific CTL cytotoxic
      activity were tested by CCK-8 assay. The mice in each group were challenged with
      lethal dose of CVB3,  and the serum virus titer was assayed and the protection
      efficacy against Coxsackievirus infection was observed. RESULTS: It was observed
      that the titers of CVB3 VP1 specific IgG and neutralizing antibody,  non-specific
      lymphocytic proliferation activity and specific lymphocytic CTL cytotoxic
      activity of the rAd/MDC-VP1 prime-pcDNA3/MDC-VP1 boost group were much higher
      than those of the rest groups(P<0.05),  what's more,  after CVB3 challenged,  the
      serum virus titer of this group was lower and the protection rate(41.67%) was
      higher (P<0.05). CONCLUSION: Both the cellular and humoral immune responses in
      mice could be significantly enhanced by the rAd/MDC-VP1 prime-pcDNA3/MDC-VP1
      boost strategy and the protection rate after challenged by lethal dose of virus
      could be increased.

PMID- 22394628
TI  - [Effect of CsA bleomycin-induced interstitial pulmonary disease in mice].
AB  - AIM: To observe the therapeutic effect of cyclosporine A (CsA) on bleomycin (BLM)
      induced pulmonary fibrosis and to investigate its mechanism. METHODS: One hundred
      and twenty C57BL/6 female mice were divided randomly into five groups:  BLM model
      group,  control saline group,  CsA30 mg treatment group,  CsA50 mg treatment
      group and control treatment group. Treatment groups and model groups were
      administrated BLM intratracheally to induce interstitial pulmonary disease model,
      with control saline group administrated with equal volume of normal saline
      instead. Mice in treatment groups were intraperitoneal injected with CsA,  while
      control treatment group were injected with equal volume of normal saline instead.
      On the 4th,  7th and 14th day after administration,  8 mice of each group were
      sacrificed,  and the peripheral blood was obtained to count total leucocytes with
      counting chamber and quantify CD4(+); T cells,  CD14(+); monocytes and CD19(+); B
      cells by flow cytometry (FCM). Bronchoalveolar levage fluid was harvested for
      cell counting and Giemsa staining. Lung tissues were harvested for
      immunohistochemical staining and pathological examination. RESULTS: The quantity
      of total leucocyte was higher in BLM model group than those in control saline
      group.The proportion of CD14(+); T cells and CD19(+);B cells in BLM model group
      were increased markedly than those in control saline group on the 4th,  7th and
      14th day post BLM. With CsA treatment,  The proportion of CD14(+); T cells was
      lower than BLM model group at the same time point,  especially on the 4th day.
      The proportion of CD19(+); B cells were significantly lower than those of BLM
      model group at the same time point(7 d,  14 d). The total and classification of
      cells of BLM model group were increased markedly than those in control saline
      group,  and decreased obviously in the treatment groups at the same time point.
      Examination of lung tissues:  With the prolonged time of BLM administration,  it
      showed wider alveolar septum,  more collagen deposition,  as well as more
      infiltrating inflammatory cells which consisted of generous lymphocyte and few
      mononuclear macrophages than those in saline control group. With the prolonged
      time of CsA injection,  the interstitial pulmonary inflammation was remissive, 
      and there was less fibroblast infiltration and collagen deposition in pulmonary
      interstitium and periphery of bronchiole. Alveolar epithelial cells,  bronchiolar
      epithelial cells,  mononuclear macrophages,  neutrophils and lymphocytes were
      demonstrated to express CD147,  there was higher CD147 expression in BLM model
      group than those in CsA treatment groups. CONCLUSION: CsA may heal BLM induced
      interstitial pulmonary disease by blocking CD147-CypA interaction,  then
      decreasing chemotaxis for the immunocyte,  and reducing migration of immunocytes
      to the lung and collagen deposition in the lung.

PMID- 22394629
TI  - [Expression and localization of ArgBP2 in osteosarcoma MG-63 cells].
AB  - AIM: To construct an eukaryotic expression vector GFP-hArgBP2 and identify the
      expression and localization of hArgBP2 in osteosarcoma MG-63 cells. METHODS:
      Using pcDNA3.1-hArgBP2 as a template,  we obtained human ArgBP2 coding sequence
      by polymerase chain reaction (PCR) amplification and cloned it into the
      eukaryotic expression vector. The insert was identified by restriction enzyme
      digestion and DNA sequencing. GFP-hArgBP2 was transfected into osteosarcoma MG-63
      cells and examined by Western blot. The localization of GFP-hArgBP2 in MG-63
      cells was also observed with laser scanning confocal microscopy. hArgBP2 protein
      was purified by immunoprecipitation assay. RESULTS: hArgBP2 was successfully
      constructed into the expressing vector pEGFP-C1. The length of the fragment
      identified by restriction enzyme digestion was 1 935 bp. The expression of GFP
      hArgBP2 fusion protein with a molecular weight of 97 000Da was detected by
      Western blot and pulled down by GFP antibody,  and its localization was  in the
      cytoplasm and perinucleus in MG-63 cells. CONCLUSION: The recombinant plasmid of
      hArgBP2 gene was successfully constructed. The expression of GFP-hArgBP2 fusion
      protein was identified and pulled down by GFP antibody. GFP-hArgBP2 was mainly
      localized in the cytoplasm and perinucleus of MG-63 cells.

PMID- 22394630
TI  - [Alpha lipoic acid affect the function of EPCs incubated by high-glucose].
AB  - AIM: EPCs were cultured in high-glucose-medium to induce oxidative stress.
      Concentration of malonaldehyde (MDA) and nitrogen monoxidum (NO) in culture
      medium were measured. The function of EPCs and protein expression of GPx-1 and
      eNOS were determined. Antioxidant alpha lipoic acid (ALA) was used as an
      intervention factor to explore the mechanism by which glucose induces the damage
      of EPCs. METHODS: EPCs were isolated and cultured from 15 Wistar rats (180-200
      g). After planted for 4 days and 24 hours of attachment,  cells were treated in 3
      conditions:  normal control group (NC) were cultured with  5 mmol/L glucose; 
      high-glucose group (HS) were cultured with 30 mmol/L glucose;  ALA group were
      cultured with 30 mmol/L glucose+ ALA(40 MUg/L). Protein and gene expression of
      GPx-1 and eNOS were determined by Western blot and reverse transcription(RT-PCR);
      NO,  MDA levels in culture medium were measured after 48 hours of treatment.
      RESULTS: (1) Effect of different treatment on the secretion of MDA in EPCs: MDA
      levels in medium treat with high glucose (HS group) after 48h was significantly
      higher than that in NC group (P<0.05)  and  decreased after ALA intervention. 
      (2) Effect of different treatment on the protein expression of GPx-1 in EPCs: 
      Protein expression of GPx-1 was significantly lower in EPCs treated with high
      glucose than that in NC group after 48 hours of treatment while significantly
      normalized after ALA intervention (P<0.05). (3) Effect of different treatment on
      eNOS expression and NO secretion:  eNOS expression was significantly lower in
      EPCs treated with high glucose than that in NC group after 48 hours of treatment
      (P<0.05). NO levels in medium was lower in HS group than in NC group (P<0.05). 
      eNOS expression and NO level were increased after ALA intervention compared with
      HS group(P<0.05). CONCLUSION: High-glucose culture induces oxidative stress in
      EPCs, EPCs cultured in high-glucose medium displays an impaired function shown as
      an lower anti-oxidative capacity,  decreased eNOS expression and NO secretion,
      Impaired anti-oxidative capacity and NO secretion by high-glucose treatment can
      be improved by ALA intervention.

PMID- 22394631
TI  - [Prokaryotic expression and purification of human GST-Cdc25C fusion protein and
      preliminary detection of its function].
AB  - AIM: To clone prokaryotic expression vector of Cdc25C,  purify the fusion protein
      of GST-Cdc25C,  and identify its function preliminarily. METHODS: Human Cdc25C
      coding region was amplified from human mammary cDNA library by PCR,  and cloned
      into the prokaryotic expression vector pGEX-KG. The fusion protein GST-Cdc25C was
      expressed in E.coli Rossate and purified by GST-Sepharose 4B beads. The function
      of purified GST-Cdc25C was identified by GST pull-down assay. RESULTS: The GST
      Cdc25C recombinant plasmid was successfully obtained by double  digestion
      identification. The inserted fragment was confirmed correctly  by sequencing. SDS
      PAGE and Western blot analysis showed that the fusion protein was expressed. The
      fusion protein of about M(r); 80 000 was successfully induced,  and identified by
      SDS-PAGE and Western blot analysis. GST pull-down assay showed that GST-Cdc25C
      could interact with Chk2 which verified its known function. CONCLUSION: Cdc25C
      was successfully cloned and purified.

PMID- 22394632
TI  - [Eukaryotic expression and biological activity of recombinant human IL-17B
      protein].
AB  - AIM: To construct pCEP4/hIL-17B recombinant expression vector and express it
      stably in eukaryotic cells and investigate the biological activity in vitro.
      METHODS: The CDS region of human IL-17B gene was cloned by RT-PCR. After
      identification by sequencing,  the hIL-17B gene was inserted into expression
      vector of pCEP4 to construct the recombinant vector pCEP4/hIL-17B,  then
      transfected into 293T cells. The transgenic 293T cell line stably expressing rhIL
      17B protein was selected in the presence of Hygromycin B. After FCS-free
      cultivation and sub-cloning,  The IL-17B/mFc gene and protein expression was
      confirmed by RT-PCR,  ELISA and Western blot analysis. To investigate the ability
      of combination with IL-17B receptor on human leukemic monocytic cell line,  THP
      1,  by Flow cytometrical analysis (FACS) and of stimulation to secret cytokines
      in vitro. RESULTS: The recombinant pCEP4/hIL-17B and its transgenic 293T cells
      stably expressing rhIL-17B protein were obtained successfully. FACS analysis
      showed its high affinity with its receptor and it can stimulated THP-1 cell line
      to excrete IL-1beta and TNF-alpha in vitro and consistently caused a dose
      dependent influx of neutrophil into the peritoneal cavity by intraperitoneal
      injection in vivo. CONCLUSION: The obtainment of transgenic 293T cell line stably
      expressing rhIL-17B protein paved the way for further study on biological
      functions of hIL-17B.

PMID- 22394633
TI  - [Effects of ribonuclease inhibitor on apoptosis and invasion of human breast
      cancer MDA-MB-231 cells].
AB  - AIM: RI gene is transfected into human breast cell line MDA-MB-231 which is
      relatively hypo-expression RI gene. To investigate how RI gene affect the cell
      apoptosis and invasion of MDA-MB-231. METHODS: (1) A recombinate pLNCX-RI and an
      empty pLNCX were transferred into MDA-MB-231 cells by using Lipofectamin(TM)
      2000. After transfection, positive clones were screened with G418 and expanded by
      culture. RT-PCR and Western blot methods were used to analyze expression of RI
      mRNA and protein in MDA-MB-231 cells before and after transfection. (2) Transwell
      test, FCM test were used to search for the effects of RI expression on
      transfected cells apoptosis and invasion. (3)To study preliminarily the related
      mechanism by which RI induced breast cancer cell apoptosis, the mRNA and protein
      expression of survivin in MDA-MB-231 cells were examined by RT-PCR and Western
      blot, and protein expression of Caspase-3 in MDA-MB-231cells were examined by
      Western blot. (4) To investigate preliminarily the mechanism by which RI
      inhibited breast cancer cell invasion, the mRNA and protein expression of CD24 in
      MDA-MB-231 cells were examined by RT-PCR and Western blot. RESULTS: (1) The RI
      gene was transfected successfully to MDA-MB-231 by using LipofectamineTM2000, the
      subclone cell lines MDA-MB-231/pLNCX-RI which highly expressed RI were
      successfully selected. (2) Compared with MDA-MB-231 and MDA-MB-231/pLNCX cells,
      the results of FCM and transwell in MDA-MB-231/pLNCX-RI cells indicated: the
      percentage of cell apoptosis were obviously increased(P<0.01), penetrating
      membrane cells were decreased(P<0.01). The mRNA and protein expression of
      Survivin were degraded, and Caspase-3 was activated in MDA-MB-231/pLNCX-RI
      cells(P<0.01). The mRNA and protein expression of CD24 were degraded in MDA-MB
      231/pLNCX-RI cells(P<0.01). CONCLUSION: (1) Exogenous RI expression may promote
      apoptosis in human breast cells MDA-MB-231 by inhibiting the expression of
      Survivin and activating caspase-3.(2) Exogenous RI expression may inhibit
      invasion in MDA-MB-231 by inhibiting expression of CD24.

PMID- 22394634
TI  - [Pharmacological mechanisms of ethyl acetate extraction of Tongbiheji for active
      T cell signaling molecules].
AB  - AIM: To confirm extracts of activity from Traditional Chinese Medicine
      TongBiHeJi,  study effect on two signaling pathways of T cells and clarify the
      pharmacological mechanisms of TongBiHeJi. METHODS: Concanavalin(ConA) were added
      successively into rats lymphocytic culture with different extracts of activity
      from Traditional Chinese Medicine. After 24 hours,  CD71 expression rate on rat T
      lymphocytes activated with ConA was analyzed by flow cytometry. TCR,  CD28 and
      ICOS on T cells were detected after T lymphocytes of rat activated by ConA were
      cultivated with various EthylAcetate extraction of TongBiHeJi(TBHJ) and
      Methotrexate (MTX) for 48 hours. RESULTS: CD71 expression rate on rat T
      lymphocytes induced by ConA was increased to 69.7%. TBHJ inhibited   the rate of
      CD3(+);CD71(+); expression(32.5%); ConA up-regulated TCR,  CD28 and ICOS
      expression on T cells obviously. There was different between ConA and positive
      control significantly(P<0.001). TBHJ could down-regulate obviously TCR, CD28 and
      ICOS expression on ConA-activated T lymphocytes with Concentration-dependent,
      especially ICOS. MTX inhibited CD3(+);CD71(+); and CD3(+);TCR(+); expression
      also. CONCLUSION: TBHJ  inhibited T cells activation by adjusting two signaling
      pathways. That implied TBHJ could block CD28-ICOS signaling molecules to induce
      immunological tolerance. This study provided an experimental basis for
      application of TongBiHeJi to treatment of rheumatoid arthritis.

PMID- 22394635
TI  - [The effect on the pro-inflammatory role of N9 microglia exposured to hyperoxia
      after preconditioning with lipopolysaccharide in vitro].
AB  - AIM: To observe the time-dapendcrt expression of TLR4 and TNF-alpha of N9
      microglia exposured to normobaric hyperoxia after preconditioning with
      lipopolysaccharide in vitro and to explore the role of hyperoxia on the pro
      flammation response of microglia and mechanism. METHODS: N9 microglia cell line
      cultured in vitro was randomly divided into six groups(n=3): normoxia group, sLPS
      group(100 ng/mL), hLPS group(1 mg/L), hyperoxia group, hyperoxia+sLPS group(100
      ng/mL), hyperoxia+hLPS group(1 mg/L). Each of the last two groups, 30 min after
      pretreatment with different level of LPS, was subjected to 900 mL/L hyperoxia for
      various times (2 h, 6 h, 12 h, 24 h and 48 h). The remanent groups was cultured
      in ambient O(2); in which sLPS group and hLPS group respectively was treated with
      100 ng/mL and 1 mg/mL LPS in the cell supernatant. After treatment, at each time
      point, the cells of each group was harvested and TLR4 gene expression were
      observed by RT-PCR. TLR4 protein expression at 12 h was observed by Western
      blotting. TNF-alpha concentrations in the supernatant of cultured microglia N9
      cells at different time points were tested with ELISA. RESULTS: After 6 h in hLPS
      group and 16 h in sLPS group, the expression of TLR4 mRNA was gradually
      increased(P<0.05), following with increasing time and concentration of LPS, which
      reached to the maximum at 24 h in hLPS group. Compared with hLPS group,
      hyperoxia+hLPS group showed downregulation of TLR4 mRNA at each time point after
      6 h(P<0.05), especially at 16 h and 24 h. At 12 h, the level of TLR4 protein of
      hyperoxia+sLPS group and hyperoxia+hLPS group respectively was lower than the
      corresponding concentration of LPS group. The result of ELISA show that at each
      time point, compared with the corresponding concentration of LPS group
      respectively, the expression of TNF-alpha of hyperoxia+sLPS group and
      hyperoxia+hLPS significantly increased(P<0.05). CONCLUSION: Hyperoxia enhance the
      pro-flammation response of N9 microglia triggered by LPS and TLR4 may be the
      important negative-control target molecule.

PMID- 22394636
TI  - [The expression and significance of TLR4, MyD88 and NF-kappaB mRNA in mouse lymph
      node of experimental autoimmune myositis].
AB  - AIM: To investigate TLR4, MyD88 and NF-kappaB mRNA levels in mouse lymph node
      with experimental autoimmune myositis(EAM)and determine the role of TLR4 in
      autoimmune myositis. METHODS: Thirty femal BALB/c mice were randomly divided into
      five groups (n=6  animals per group): group 1 was the control,  while animals in
      other four groups were killed at different time point: group 2 in the first week,
      group 3 in the second week,  group 4 in the third week and group 5 in the fourth
      week since they had been given myosin for preparing EAM. The expressions of TLR4,
      MyD88 and NF-kappaB mRNA were measured with real-time fluorescent quantitative
      polymerase chain reaction. RESULTS: (1)The expressions of TLR4, MyD88 and NF
      kappaB mRNA in each EAM group were significantly high compared with those in the
      normal control group,  which was significantly highest in group 3 of all(P<0.01)
      and significantly higher in group 4 than in group 5(P<0.01).(2)The expression
      level of TLR4 mRNA had significant positive correlations with the expressions of
      MyD88 mRNA and NF-kappaB mRNA(r=0.906, r=0.967,  P<0.01),  and the latter two
      also had significant positive correlations(r=0.919, P<0.01). CONCLUSION: TLR4
      played an important role in the development of autoimmune myositis and run its
      function mainly by MyD88-dependent pathway that could activate NF-kappaB for
      promoting the release of inflammatory factors.

PMID- 22394637
TI  - [Preparation and characterization of monoclonal antibody against Vibrio
      vulnificus].
AB  - AIM: To prepare high-performance and specific monoclonal antibody (mAb) against
      Vibrio vulnificus and carry out characterization. METHODS: BALB/c mice were
      immunized with Vibrio vulnificus protein, and hybridoma cells against Vibrio
      vulnificus were produced by cellsion technique. The titers of mAbs against vvhA
      and cross-reaction between the anti-vvhA mAb and other other important marine
      bacteria were screened by ELISA and Western blot. RESULTS: Five strains of
      hybridoma were obtained. Identification result indicated that 5 mAbs have
      favourable specifity and immunoreactivity. CONCLUSION: Specific mAbs against
      Vibrio vulnificus were produced which provides an important preparation for
      establishing rapid-detection kit of detecting Vibrio vulnificus.

PMID- 22394638
TI  - [Characteristics of gammadelta T cell subsets induced from peripheral blood
      mononuclear cells of HIV/AIDS patients in vitro].
AB  - AIM: To investigate the characteristics of gammadelta T cell subsets in
      peripheral blood and Vdelta1 and Vdelta2 T cell subsets proliferation after
      induction in vitro,  and to provide experimental basis for gammadelta T cells
      expansion methods in vitro. METHODS: Percentages of gammadelta T cells,  Vdelta1
      and Vdelta2 T cells in CD3 T cells from 25 cases of HIV/AIDS patients (HIV group)
      and 31 cases of healthy adults as control (HC group) were investigated with flow
      cytometry (FCM);  and 10 cases peripheral blood mononuclear cells (PBMCs) from
      each group were induced and cultured for 14 d by using anti-gammadelta TCR mAb
      and IL-2,  then the cell amounts were counted,  gammadelta T cells and Vdelta1, 
      Vdelta2 T cells were detected and analyzed with flow cytometry (FCM) at 0 d,  7 d
      and 14 d. RESULTS: The percentages and absolute counts of gammadelta T cells and
      V delta2 T cells in HIV group were significantly lower than those in HC group, 
      but those of Vdelta1 subsets were significantly higher than those of HC group.
      After culture for 14 day, the total cell amount of HC group expanded almost 3
      times,  but those of HIV group expanded a little;  The percentages of gammadelta
      T cells in HC group were above 80%,  but those in HIV group were only about 35%; 
      the percentages of Vdelta2 T cells in HC group were about 65%,  but those in HIV
      group were only about 17%. CONCLUSION: The proportion of gammadelta T cells in
      peripheral blood of HIV/AIDS patients decreased significantly,  and
      Vdelta1/Vdelta2 ratio was inversed;  the expansion effect was not so good to use
      anti-gammadelta TCR mAb and IL-2 to induce gammadelta T  cells and Vdelta2
      subsets of HIV/AIDS,  and the Vdelta1/Vdelta2 ratio inversion could not reverse.
      More efficient culture methods should be explored.

PMID- 22394639
TI  - [Expression of pSTAT3 in non-small cell lung cancer and its clinical
      significance].
AB  - AIM: To explore the expression of phosphorylated STAT3 (pSTAT3) in non-small cell
      lung cancer(NSCLC) and its clinical significance. METHODS: The expression of
      pSTAT3 was detected in 59 cases of NSCLC and their para-cancerous tissue by
      immunohistochemical staining. RESULTS: (1) The expression of pSTAT3 in NSCLC was
      significantly higher than that in para-cancerous tissue. (2) The expression of
      pSTAT3 was associated with tumor's size and smoking status,  which was
      significantly higher in smaller tumors(diameter<3 cm) and nonsmokers than that in
      larger tumors(diameter>=3 cm) and smokers,  but was not associated with gender, 
      age,  lymph node metastasis,  clinical stage and differentiation grade. The
      percentage rate of pSTAT3 expression was higher in adenocarcinoma than that in
      squamous cell carcinoma but without statistically significant. CONCLUSION: pSTAT3
      may play an important role in the development of NSCLC and the direction  of
      targeted therapy.

PMID- 22394640
TI  - [Expression and clinical significance of cyclin E2 in nasopharyngeal carcinoma].
AB  - AIM: To explore the expressions of Cyclin E2 in nasopharyngeal carcinoma (NPC)
      and clinic opathological parameters,  and to investigate the role of Cyclin E2 in
      oncogenesis,  progress,  invasion and metastasis of NPC. METHODS: Sixty patients
      with NPC and twenty-one noncancerous nasopharyngeal epithelial samples were
      retrospectively studied from year 2000 to 2006,  The protein and mRNA expressions
      of Cyclin E2 was detected by immunohistochemical staining and RT-PCR. RESULTS:
      The protein expressions rates of Cyclin E2 were 75% and 9.5% in nasopharyngeal
      samples and noncancerous nasopharyngeal epithelial samples,  It was significantly
      higher in NPC than in normal controls (P<0.01). Furthermore,  the protein
      expression was significantly higher in NPC patients with clinical staging and
      cervical lymph node or poor prognosis than in NPC patients without(P<0.01). The
      expression in NPC was not correlated with gender or age (P>0.05).   The mRNA
      expression of Cyclin E2 was significantly higher in NPC than in normal controls
      (P<0.01). CONCLUSION: These findings demonstrate that Cyclin E2 may play
      important roles in the invasion,  metastasis,  and poor prognosis of NPC.

PMID- 22394641
TI  - [Effects and mechanisms of autophagy of trophoblast cells in severe
      preeclampsia].
AB  - AIM: To investigate the occurrence law of autophagy in trophoblast cells from
      severe preeclampsia and its possible mechanisms of wrecking cells. METHODS: 23
      cases of placenta tissues were collected from women suffer from severe
      preeclampsia and normal pregnant women respectively. Surface villous of placental
      was observed by scanning electron microscope,  and ultrastructure and
      autophagosome of trophoblast cells were observed by transmission electron
      microscopic. The expressions of Beclin-1 and LC3II in placenta tissues were
      detected by Immunohistochemical technique,  then its relevance whit weight of
      fetus and placental was analyzed. RESULTS: Compared with the control group, 
      villous were decrease in placenta tissue from patients suffer from severe
      preeclampsia,  and its arrangement was disordered;  typical autophagosomes of
      trophoblast cells were observed by transmission electron microscope. The
      expression of Beclin-1,  LC3IIwere significantly up-regulated in placenta tissue
      from patients suffer from severe preeclampsia.The correlation coefficient of
      Beclin-1,  LC3II and placental weight,  fetal weight respectively were -0.977,  
      0.930,  -0.812,  -0.849. CONCLUSION: Autophagy were significantly up-regulated in
      trophoblast cells from patients suffer from severe preeclampsia by increasing
      expression of Beclin-1,  LC3II protein,  and its expression was negatively
      related to weight of fetus and placental.

PMID- 22394642
TI  - [Clinical significance of detecting partial cytokines in serum of patients with
      pulmonary tuberculosis by cytometric bead array].
AB  - AIM: To explore the clinical significance of cytometric bead array(CBA) in
      detecting partial cytokines(IL-2,  IL-4,  IL-6,  IL-10,  TNF-alpha and IFN
      gamma)in the serum from patients with different types of pulmonary tuberculosis.
      METHODS: The levels of six cytokines (IL-2,  IL-4,  IL-6,  IL-10,  TNF-alpha and
      IFN-gamma) in the serum from 84 cases of patients with pulmonary tuberculosis(46
      cases of active pulmonary tuberculosis patients,  38 cases of inactive pulmonary
      tuberculosis patients) and 30 cases of normal person,   were detected by BD CBA
      Flex Set kit. RESULTS: The levels of IL-2, IL-4, IL-6, IL-10, TNF-alpha and IFN
      gamma in pulmonary tuberculosis group were significantly higher than those in
      control group (P<0.01 or P<0.05.Compared with the inactive pulmonary tuberculosis
      group, the levels of serum IL-2, IL-4, IL-6, IL-10, TNF-alpha and IFN-gamma in
      the active pulmonary tuberculosis group were significantly higher (P<0.01 or
      P<0.05).Serum IL-4 and TNF-alpha levels in active pulmonary tuberculosis group, 
      inactive pulmonary tuberculosis group and the control group had not significantly
      different. CONCLUSION: Six  cytokines in serum  can be detected    quickly and
      sensitively in batches at one   time  by CBA. IL-2, IL-4, IL-6, IL-10, TNF-alpha
      and IFN-gamma play an important role in the immune pathogenesis of pulmonary
      tuberculosis.

PMID- 22394643
TI  - [The expression and clinical significance of IL-17AR on peripheral blood B cells
      of patients with systemic lupus erythematosus].
AB  - AIM: To investigate the expressions of Interleukin-17A receptor (IL-17AR) on the
      peripheral blood B lymphocytes of SLE patients and to analyze the correlations
      between IL-17AR and clinical parameters. METHODS: Expression of IL-17AR on
      peripheral blood CD19(+);B lymphocytes were analyzed in 60 SLE patients and 33
      healthy controls by flow cytometry. The difference of IL-17AR expression levels
      in two groups were compared. Furthermore, the correlation between IL-17AR
      expressions and clinical some measures, such as ESR, CRP, complement 3(C3),
      complement 4(C4), the amount of serum IgG, anti double strands DNA antibody, anti
      nuclear antibody, SLEDAI score and urine protein excretion were analyzed.
      RESULTS: Compared with healthy subjects, the proportions of B cells expressing IL
      17AR were higher among SLE patients. In SLE patients, groups with mouth ulcer,
      serositis, renal lesions or immunologic abnormality were higher than the negative
      groups separately. The positive correlations were observed between IL-17AR
      expression levels and clinical measure of the SLEDAI, CRP and serum triglyceride
      level. The negative correlation was observed between IL-17AR expression levels
      and clinical measure of the serum indirect bilirubin level, serum albumin level.
      CONCLUSION: Interleukin-17A receptor expression increased on peripheral blood B
      cells of SLE patients, and correlate with clinical measures.

PMID- 22394644
TI  - The recommendations of the ICRP vis-a-vis the Fukushima Dai-ichi NPP accident
      aftermath.
AB  - The International Commission on Radiological Protection (ICRP) created a Task
      Group (ICRP TG84) on the initial lessons learned from the nuclear accident at the
      Fukushima Dai-ichi NPPs vis-a-vis the ICRP system of radiological protection. The
      ICRP TG84 is expected to compile lessons learned related to the efforts carried
      out to protect people against radiation exposure during and after the emergency
      exposure situation caused by the accident and, in light of these lessons, to
      consider ad hoc recommendations to strengthen the ICRP system of radiological
      protection for dealing with this type of emergency exposure. The Chairman of ICRP
      TG84 presents in this paper his personal views on the main issues being
      considered by the group at the time of the Fukushima Expert Symposium. ICRP TG84
      expects to finalize its work by the end of 2012.

PMID- 22394645
TI  - Liquid-solid interfaces: structure and dynamics from spectroscopy and
      simulations.

PMID- 22394646
TI  - Association between indicators of dementia and nutritional status in
      institutionalised older people.
AB  - BACKGROUND AND AIMS: Dementia weakens older people and can lead to malnutrition;
      therefore, the objective of this study was to assess the association between
      indicators of dementia and biochemical indicators, anthropometric indicators and
      food intake in institutionalised older people. METHODS: A total of 150 older
      people of both genders participated in this study. Nutritional status was
      determined by body mass index and other anthropometric variables, and biochemical
      indicators were used to analyse the differences between individuals with and
      without dementia. Energy and nutrient intakes were determined by food records,
      and dementia was investigated with the Mini-Mental State Examination. The data
      were analysed by the chi-square test, Student's t-test and Mann-Whitney tests.
      RESULTS: Of the 150 individuals studied, 48% were men with a mean age of 73 +/-
      10 years and 52% were women with a mean age of 80 +/- 9 years. Thirty-six per
      cent had some degree of malnutrition and 48% presented dementia, which was more
      prevalent in women (59%). The nutritional status of men and women individuals
      with and without dementia differed significantly (P < 0.001 for men and women).
      The only variables that presented a significant difference between individuals
      with and without dementia were those associated with muscle mass in men. There
      were no differences in energy and nutrient intakes between individuals with and
      without dementia except for vitamin C intake, which differed among women (P =
      0.032). CONCLUSION: In the conditions of the present study, dementia was
      associated with nutritional status, but not with energy and nutrient intakes,
      suggesting that older people with dementia may have higher nutritional
      requirements. Implications for practice.  Investigation of dementia may
      contribute to the nutritional status assessment of older people and energy
      expenditure and immobility should be investigated for a more complete assessment.

PMID- 22394647
TI  - Effects of a pre-visit educational website on information recall and needs
      fulfilment in breast cancer genetic counselling, a randomized controlled trial.
AB  - INTRODUCTION: Pre-visit education which helps counselees to prepare for their
      first visit for breast cancer genetic counseling might enhance information recall
      and needs fulfilment. This study assessed the effects of a pre-visit website with
      tailored information and question prompt sheet (QPS), named E-info geneca.
      METHODS: A total of 197 counselees were randomized to receive usual care (UC) or
      UC plus E-info geneca. All counselees completed a pre- and post-visit
      questionnaire and visits were videotaped. We studied effects on counselees'
      information recall, knowledge about breast cancer and heredity, fulfillment of
      needs, risk perception alignment, anxiety and perceived personal control, using
      multilevel regression analyses. RESULTS: Intent-to-treat analysis showed that
      counselees in the intervention group (n = 103) had higher levels of recall of
      information from the consultation (beta = .32; confidence interval (CI): .04 to
      .60; P = .02; d = .17) and post-visit knowledge of breast cancer and heredity
      (beta = .30; CI: .03 to .57; P = .03) than counselees in the UC group (n = 94).
      Also, intervention group counselees reported better fulfilment of information
      needs (beta = .31; CI: .03 to .60; P = .03). The effects of the intervention were
      strongest for those counselees who did not receive an indication for DNA testing.
      Their recall scores showed a larger increase (beta = .95; CI: .32 to 1.59; P =
      .003; d = .30) and their anxiety levels dropped more in the intervention compared
      to the UC group (beta = -.60; CI: -1.12 to -.09; P = .02). No intervention
      effects were found after the first visit on risk perception alignment or
      perceived personal control. CONCLUSIONS: This study shows that pre-counseling
      education, using tailored information technology, leads to more effective first
      visits for breast cancer genetic counseling, in particular for counselees who
      received no indication for DNA testing and, therefore, had no indication for a
      second visit. Future study should focus on the effects of a pre-visit website on
      the outcomes after a complete series of visits. TRIAL REGISTRATION: Dutch Trial
      Register ISRCTN82643064.

PMID- 22394648
TI  - Bronchodilatory effect of inhaled budesonide/formoterol and budesonide/salbutamol
      in acute asthma: a double-blind, randomized controlled trial.
AB  - BACKGROUND: There are no published studies that have compared bronchodilatory
      effect of inhaled budesonide/formoterol combination with budesonide/salbutamol
      delivered by metered dose inhaler with a spacer in acute exacerbation of asthma
      in children. We, therefore, compared the bronchodilatory effects of inhaled
      budesonide/formoterol (dose: 200 MUg and 12 MUg respectively) combination with
      budesonide (200 MUg)/salbutamol (200 MUg) administered by metered dose inhaler
      and spacer in children of 5-15 years with mild acute exacerbation of asthma
      [Modified Pulmonary Index Score (MPIS) between 6-8] in this double-blind,
      randomized controlled trial. The primary outcome was FEV1 (% predicted) in the
      two groups at 1, 5, 15, 30, 60 min after administration of the study drug.
      RESULTS: We did not observe any significant differences in the % predicted FEV1
      and MPIS between formoterol and salbutamol at various time points from 1 min to
      60 min post drug administration. There was significant improvement in FEV1 (%
      predicted) from baseline in both the groups as early as 1 min after drug
      administration. CONCLUSIONS: Salbutamol or formoterol delivered along with
      inhaled corticosteroid by metered dose inhaler with spacer in children between 5
      15 years of age with mild acute exacerbation of asthma had similar
      bronchodilatory effects. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00900874.

PMID- 22394649
TI  - Comments on manuscript entitled "Status of cellular immunity lacks prognostic
      significance in vulvar squamous carcinoma" by de Jong RA et al. Gynecol Oncol.
      (2012), doi:10.1016/j.ygyno.2011.12.416.

PMID- 22394651
TI  - Hungary health system review.
AB  - Hungary has achieved a successful transition from an overly centralized,
      integrated Semashko-style health care system to a purchaser provider split model
      with output-based payment methods. Although there have been substantial increases
      in life expectancy in recent years among both men and women, many health outcomes
      remain poor, placing Hungary among the countries with the worst health status and
      highest rate of avoidable mortality in the EU (life expectancy at birth trailed
      the EU27 average by 5.1 years in 2009). Lifestyle factors especially the
      traditionally unhealthy Hungarian diet, alcohol consumption and smoking play a
      very important role in shaping the overall health of the population.In the single
      payer system, the recurrent expenditure on health services is funded primarily
      through compulsory, non-risk-related contributions made by eligible individuals
      or from the state budget. The central government has almost exclusive power to
      formulate strategic direction and to issue and enforce regulations regarding
      health care. In 2009 Hungary spent 7.4% of its gross domestic product (GDP) on
      health, with public expenditure accounting for 69.7% of total health spending,
      and with health expenditure per capita ranking slightly above the average for the
      new EU Member States, but considerably below the average for the EU27 in 2008.
      Health spending has been unstable over the years, with several waves of increases
      followed by longer periods of cost-containment and budget cuts. The share of
      total health expenditure attributable to private sources has been increasing,
      most of it accounted for by out-of-pocket (OOP) expenses. A substantial share of
      the latter can be attributed to informal payments, which are a deeply rooted
      characteristic of the Hungarian health system and a source of inefficiency and
      inequity. Voluntary health insurance, on the other hand, amounted to only 7.4% of
      private and 2.7% of total health expenditure in 2009. Revenue sources for health
      have been diversified over the past 15 years, but the current mix has yet to be
      tested for sustainability. The fit between existing capacities and the health
      care needs of the population remains less than ideal, but improvements have been
      made over the past 15 years. In general, the average length of stay and hospital
      admission rates have decreased since 1990, as have bed occupancy rates. However,
      capacity for long-term nursing care in both the inpatient and outpatient setting
      is still considered insufficient. Hungary is currently also facing a health
      workforce crisis, explained by the fact that it is a net donor country with
      regard to health care worker migration, and health care professionals on the
      whole are ageing. Although the overall technical efficiency of the system has
      increased considerably, mainly due to the introduction of output-based payment
      systems, allocative efficiency remains a problem. Considerable variations exist
      in service delivery both geographically and by specialization, and equity of
      access is far from being realized, a fact which is mirrored in differing health
      outcomes for different population groups. A key problem is the continuing lack of
      an overarching, evidence-based strategy for mobilizing resources for health,
      which leaves the health system vulnerable to broader economic policy objectives
      and makes good governance hard to achieve. On the other hand, Hungary is a target
      country for cross-border health care, mainly for dental care but also for
      rehabilitative services, such as medical spa treatment. The health industry can
      thus be a potential strategic area for economic development and growth.

PMID- 22394653
TI  - Neonates presenting with severe complications of frenotomy: a case series.
AB  - INTRODUCTION: Tongue-tie or ankyloglossia is an anatomic variation in which the
      lingual frenulum is thick, short or tight. It may be asymptomatic, or present
      with complications like breast feeding difficulties or speech, dental and
      cosmetic problems. The treatment of this condition, where indicated, is
      frenotomy. This procedure usually has few or no complications. However, when it
      is done by untrained personnel, it may lead to life-threatening complications.
      This paper highlights complications that could arise from improper treatment of
      ankyloglossia. CASE PRESENTATION: Case 1 was a one-day-old male neonate, a
      Nigerian of Igbo ethnicity, who was admitted with bleeding from the mouth and
      passage of dark stools after clipping of the frenulum by a traditional birth
      attendant. He was severely pale and in hypovolemic shock, with a severed frenulum
      which was bleeding actively. His packed cell volume was 15%. He was resuscitated
      with intravenous fluids and a blood transfusion. The bleeding was controlled
      using an adrenaline pack. He also received antibiotics. He was discharged five
      days later.Case 2 was a three-day-old male neonate, a Nigerian of Ikwerre
      ethnicity, who was admitted with profuse bleeding from a soft tissue injury under
      the tongue, after clipping of the frenulum by a community health worker. He was
      severely pale and lethargic. He was resuscitated with intravenous fluids and a
      blood transfusion. The bleeding vessel was ligated with repair of the soft
      tissue. He also received antibiotics and was discharged home one week later.
      CONCLUSION: Treatment of tongue-tie, a benign condition, when done by untrained
      personnel may result in life-threatening complications. Clinicians should pay
      more attention to parents' worries about this condition and give adequate
      counseling or refer them to trained personnel for surgical intervention where
      clinically indicated.

PMID- 22394652
TI  - Evolutionary game dynamics in populations with different learners.
AB  - We study evolutionary game theory in a setting where individuals learn from each
      other. We extend the traditional approach by assuming that a population contains
      individuals with different learning abilities. In particular, we explore the
      situation where individuals have different search spaces, when attempting to
      learn the strategies of others. The search space of an individual specifies the
      set of strategies learnable by that individual. The search space is genetically
      given and does not change under social evolutionary dynamics. We introduce a
      general framework and study a specific example in the context of direct
      reciprocity. For this example, we obtain the counter intuitive result that
      cooperation can only evolve for intermediate benefit-to-cost ratios, while small
      and large benefit-to-cost ratios favor defection. Our paper is a step toward
      making a connection between computational learning theory and evolutionary game
      dynamics.

PMID- 22394650
TI  - Cellular therapies for treating pain associated with spinal cord injury.
AB  - Spinal cord injury leads to immense disability and loss of quality of life in
      human with no satisfactory clinical cure. Cell-based or cell-related therapies
      have emerged as promising therapeutic potentials both in regeneration of spinal
      cord and mitigation of neuropathic pain due to spinal cord injury. This article
      reviews the various options and their latest developments with an update on their
      therapeutic potentials and clinical trialing.

PMID- 22394654
TI  - Orexins increase penicillin-induced epileptic activity.
AB  - Orexins have been implicated with physiological function including sleep-wake
      cycle, energy homeostasis, drinking behavior, analgesia, attention, learning and
      memory but their effects on excitability are controversial. We investigated the
      effects of intracortical injections of orexin A (100 pmol) and B (100 pmol) on
      the electrophysiological manifestation of epileptic seizures induced by cortical
      penicillin application in adult male rats. In comparison to saline, orexin A and
      B enhanced significantly the spike number, spike amplitude and spectral power
      values induced by cortical penicillin. Our findings indicates that orexins
      enhances the hyperexcitable and hypersyncronic cortical epileptic activity
      induced by focal application of penicillin-G.

PMID- 22394655
TI  - Regarding 'National Health and Hospital Reform Commission final report and
      patient-centred suggestions for reform' by T. Jowsey, L. Yen, R. Wells and S.
      Leeder.
AB  - The recently published article by Jowsey et al. (2011, Australian Journal of
      Primary Health 17, 162-168) highlighted key inclusions and omissions from the
      National Health and Hospital Reform Commission final report with respect to
      patient-centred care for people with chronic illness. However, the author
      proposes that this study could have further addressed dimensions of equity and
      patient-centred practice by including participants with chronic mental illness.
      The author suggests that interventions to improve chronic illness care typically
      remain disease specific, which fails to address the realities that face consumers
      or service providers. References to the literature and professional experience
      are provided to support the inclusion of mental illness within discussion,
      services and policy concerning chronic illness.

PMID- 22394656
TI  - Historical overview of church involvement in health and wellbeing in Australia:
      implications for health promotion partnerships.
AB  - Health promotion practice requires partnerships with different sectors of society
      and at all levels of government to achieve health equity as the prerequisites for
      health include domains that exist outside of the health sphere. Therefore
      existing partnerships for health need to be strengthened and the potential for
      new partnerships must be considered in order to address health holistically. The
      literature base exploring the church as a partner and setting for health
      promotion is predominantly from the US and therefore there is a need for research
      exploring the opportunities and challenges of partnering with churches in the
      Australian context. This paper presents an historical overview of the involvement
      of churches and church affiliated organisations in health and welfare in
      Australia recognising that while some of the values, practices and beliefs of
      churches may have considerable synergies with health promotion, others may be
      sources of contention or difference.

PMID- 22394657
TI  - Approaches for prioritising the nutritional needs of refugee communities.
AB  - An important part of health promotion planning is identifying priority areas for
      programs. A typical approach includes a needs assessment where a deficit-oriented
      approach captures problems within a community. Approaches that focus on strengths
      have emerged as potentially more appropriate and effective methods for program
      planning. This report describes the outcomes and learning from using both a
      deficit-oriented and strength-based approach for identifying and describing
      nutrition priorities of refugee communities. Focus groups (n=11) were conducted
      using both methods with a total of 69 community members from Afghan, Burmese and
      Sudanese backgrounds. Analysis of the focus group transcripts using a content
      analysis approach identified key influences on food choice and determinants of
      health and nutrition. There were differences in the type of information obtained
      from the deficit-oriented and strength-based approach. Although the strength
      based approach was unfamiliar to participants and offered several challenges, it
      identified unique aspects of the communities that were not identified by the
      deficit-oriented approach, and could be used as the basis for planning community
      health promotion strategies. Elements of each method should be considered when
      designing community program planning strategies.

PMID- 22394658
TI  - Service integration for the dually diagnosed.
AB  - The needs of dually diagnosed clients in mental health services have been and
      remain a focus for service development and improvement in Australia. The Council
      of Australian Governments committed to a five-year National Action Plan on Mental
      Health with a $1.8 billion injection into mental health services. In Australia
      there have been great advances in the service initiatives and service
      deliverables to those clients who experience a dual diagnosis. These advances
      include that dual diagnosis is systematically identified and responded to in a
      timely, evidence-based manner as a core business in mental health and alcohol and
      other drug services. These advances are brought to life by specialist mental
      health and alcohol and other drug services that establish effective partnerships
      and agreed mechanisms to support integrated care and collaborative practice.
      Here, four case studies are offered as a means of illustrating the ways in which
      projects undertaken in local community health services have approached dual
      diagnosis treatment for clients. These case studies reflect how cooperation and
      cross-referral between services, as well as effective management of dual
      diagnosis clients by suitably qualified staff can produce benefits to clients who
      use the service.

PMID- 22394659
TI  - Health home visiting for vulnerable families: what has occurred and what is yet
      to arrive?
AB  - Sustained health home visiting (SHHV) is a valuable means of implementing early
      intervention for vulnerable families with infants or young children. This first
      of a two-part report describes clients and identifies nurses' activities with or
      on behalf of clients as part of a pilot SHHV program undertaken within a
      socioeconomically disadvantaged suburban area of Sydney, New South Wales,
      Australia. A forthcoming report describes the results of the intervention. Child
      and family health nurses visited vulnerable clients who were pregnant and/or had
      an infant aged 36 months or younger. Interventions consisted of direct and
      indirect (i.e. services involving a third party) client contact. Nurses
      documented all activities undertaken with or on behalf of clients using pre
      determined codes. Over 29 months, the program accepted 136 referrals and 118
      (87%) consented to the evaluation. Families had a mean of eight risk factors,
      which commonly included current mental health symptoms or disorders (49%), a
      history or current experience of domestic violence (51%) and being known to the
      Department of Community Services (40%). Nurses' most frequent interventions
      addressed the main carer's emotional and health needs, and infant development.
      Clients' level of need required coordinated care from a specialised
      multidisciplinary team, which was unavailable to program clients and their
      families.

PMID- 22394660
TI  - Australian health professionals' social media (Web 2.0) adoption trends: early
      21st century health care delivery and practice promotion.
AB  - This study was concerned with identifying reasons behind patterns of social media
      (Web 2.0) usage associated with eight of Australia's major health professions.
      Attention was given to uncovering some of the more significant motivations for
      the resistance or adoption of Web 2.0 technologies for health care delivery and
      practice promotion by Australian health professionals. Surveys were developed
      from a common set of questions with specific variations between professions
      negotiated with professional health societies. Survey questions were constructed
      in an attempt to identify Web 2.0 adoption trends. An online survey
      (www.limesurvey.org) was used to collect data. Initial data preparation involved
      the development of one integrated SPSS file to incorporate all responses from the
      eight surveys undertaken. Initial data analysis applied Frequencies and Crosstabs
      to the identified groups and provided a profile of respondents by key business
      and demographic characteristics. Of the 935 respondents, 9.5% of participants
      indicated that they used Web 2.0 for their professional work, 19.1% of them did
      not use it for work but used it for their personal needs and 71.3% of them did
      not use Web 2.0 at all. Participants have indicated that the main reason for
      'choosing not to adopt' Web 2.0 applications as a way of delivering health care
      to their patients is due to the health professionals' lack of understanding of
      Web 2.0 (83.3%), while the main reason for 'choosing to adopt' Web 2.0
      applications is the perception of Web 2.0 as a quick and effective method of
      communication (73.0%). This study has indicated that Australian health
      professionals 'choose not to adopt' Web 2.0 usage as a way of delivering health
      care primarily due to 'a lack of understanding as to how social media would be
      used in health care' (83.3%). This study identifies that Australian health
      professionals are interacting with Web 2.0 technologies in their private lives
      but are failing to see how such technologies might be used throughout their
      professions. Australian health professionals are willing to undertake online
      educational courses (n=553, 58%) designed to upskill them about how Web 2.0 may
      be used for practice promotion and health care delivery.

PMID- 22394661
TI  - Health care in patients 1 year post-stroke in general practice: research on the
      utilisation of the Dutch Transmural Protocol transient ischaemic
      attack/cerebrovascular accident.
AB  - This study evaluates the kind of aftercare that ischaemic stroke patients receive
      and the extent that aftercare fulfils the criteria of the 'Dutch Transmural
      Protocol transient ischaemic attack/cerebrovascular accident'. Fifty-seven
      patients were interviewed 1 year post-stroke about secondary prevention and
      aftercare. Forty general practitioners (GPs) completed a questionnaire about
      guidance and secondary prevention (concerning medication and lifestyle advice).
      Most patients would like to see their GP more regularly. More aftercare was
      required than was planned. The use of aspirin remained the same, fewer patients
      used statins and more used antihypertensives. Of the 40 GPs who participated, 12%
      did not apply prevention. Blood pressure, glucose and cholesterol were measured
      in 84%, 28% and 40% of patients. All of these measures were often elevated, but
      treatment was not given. Lifestyle advice was offered to one-quarter of patients.
      Considering all of the advice given in the Dutch Protocol, several aspects can be
      improved in relation to secondary prevention. Too little attention is paid to
      giving lifestyle advice, stricter medical checkups by GPs are necessary and there
      is a decrease in use of preventive medication, partly because GPs monitors use of
      medication inadequately. The use of the Dutch Protocol in aftercare can be
      improved by a more detailed description of advice.

PMID- 22394662
TI  - Medicine use of elderly Chinese and Vietnamese immigrants and attitudes to home
      medicines review.
AB  - There is a paucity of research into the perceptions of elderly Australian ethnic
      minorities towards public health services related to quality use of medicines.
      Among the six fastest growing ethnic groups in Australia, the Mandarin-speaking
      Chinese and Vietnamese constitute the largest elderly populations with poor
      English skills. This paper investigates the relationships of elderly Chinese and
      Vietnamese migrants with medicines, general practitioners and pharmacists, and
      how these relationships influence their awareness and attitudes of the home
      medicines review (HMR) program. Two semi-structured focus groups were held with a
      total of 17 HMR-eligible patients who have never received a HMR, one with Chinese
      and one with Vietnamese respondents, each in the respective community language.
      Confusion about medications and an intention to have a HMR were pronounced among
      all participants although none of them had heard of the program before
      participating in the focus groups. Respondents reported difficulties locating a
      pharmacist who spoke their native language, which contributed to an increased
      unmet need for medicine information. The Chinese group additionally complained
      about a lack of support from their general practitioners in relation to their
      medicine concerns and was adamant that they would prefer to have a HMR without
      the involvement of their general practitioner. Our results indicate a distinct
      HMR need but not use among elderly Chinese and Vietnamese eligible patients with
      poor English skills. Home medicines review service use and perceived medication
      problems are likely to improve with an increasing availability of bilingual and
      culturally sensitive health care providers.

PMID- 22394663
TI  - Timeliness of antenatal care for mothers of Aboriginal and non-Aboriginal infants
      in an urban setting.
AB  - To compare the timing of first hospital antenatal care visit by mothers of
      Aboriginal and non-Aboriginal infants, and to identify the risk and protective
      factors associated with timeliness of accessing care, mothers who delivered at
      Campbelltown hospital between October 2005 and November 2006 were surveyed on the
      maternity ward. This survey was linked to hospital administrative data.
      Gestational age at first visit to a hospital-based antenatal clinic was compared
      for mothers of Aboriginal and non-Aboriginal infants. Risks and protective
      factors associated with timing of antenatal care were also examined using Cox
      regression and Kaplan-Meier survival curves. Data on 1520 deliveries were
      included in this study. Mothers of Aboriginal infants presented slightly later to
      hospital-based antenatal clinics than mothers of non-Aboriginal infants (median
      15.6 weeks versus 14.0 weeks). This difference did not remain after adjustment
      for all risk and protective factors. The three significant factors remaining
      were: maternal smoking; not in paid employment; and residence in a disadvantaged
      suburb. The results may reflect the complex associations that exist between the
      clustering of disadvantage among families of Aboriginal infants. A multifaceted
      approach is required to improve the timeliness of hospital-based antenatal care
      for the mothers of Aboriginal infants.

PMID- 22394664
TI  - Validation of the research capacity and culture (RCC) tool: measuring RCC at
      individual, team and organisation levels.
AB  - Research capacity building (RCB) in Australia has recently focussed on strategies
      that take a whole of system approach to developing research culture at
      individual, team and organisation levels. Although a theoretical framework
      exists, no tool has been published that quantitatively measures the effectiveness
      of RCB interventions aimed at these three levels. A sample of 134 allied health
      workers was used to validate the research capacity and culture (RCC) tool. Item
      level analysis was undertaken using Cronbach's alpha and exploratory factor
      analysis, and test-retest reliability was examined using intra-class correlations
      (ICC). The tool had one factor emerge for each domain, with excellent internal
      consistency for organisation, team and individual domains (alpha=0.95, 0.96 and
      0.96 respectively; and factor loadings ranges of 0.58-0.89, 0.65-0.89 and 0.59
      0.93 respectively). The overall mean score (total) for each domain was: 5.4
      (inter-quartile range 3.9-7.7), 4.4 (IQR 2.6-6.1) and 3.9 (IQR 2.9-6) for the
      organisation, team and individual domains respectively. Test-retest reliability
      was strong for each domain: organisation ICC=0.77, team ICC=0.83 and individual
      ICC=0.82. The RCC tool has three domains measuring research capacity and culture
      at organisation, team and individual levels. It demonstrates excellent internal
      consistency and strong test-retest reliability.

PMID- 22394665
TI  - What influences Australian women to not drink alcohol during pregnancy?
AB  - There is a strong social norm against consuming alcohol during pregnancy.
      However, many women do not realise they are pregnant until the sixth week and are
      not provided with information about the risks of consuming alcohol until they
      visit a health professional in the second trimester. We conducted semi-structured
      interviews with 12 midwives and 12 pregnant women from two regions in NSW in 2008
      09 to explore attitudes towards alcohol consumption during pregnancy, and the
      factors that may encourage or inhibit women from following the recommendation to
      abstain from drinking while pregnant. Both groups noted the social issues around
      pregnant women consuming alcohol due to perceived social norms and the challenges
      in not revealing early pregnancy status at social events.

PMID- 22394666
TI  - Engaging general practice nurses in chronic disease self-management support in
      Australia: insights from a controlled trial in chronic obstructive pulmonary
      disease.
AB  - The growing burden of chronic disease will increase the role of primary care in
      supporting self-management and health behaviour change. This role could be
      undertaken to some extent by the increased practice nurse workforce that has
      occurred over recent years. Mixed methods were used to investigate the potential
      for general practice nurses to adopt this role during a 12-month randomised
      controlled study of telephone-delivered health mentoring in Tasmanian practices.
      Nurses (general practice and community health) were trained as health mentors to
      assist chronic obstructive pulmonary disease patients to identify and achieve
      personal health related goals through action plans. Of 21% of invited practices
      that responded, 19 were allocated to health mentoring; however, general practice
      nurses were unable to train as health mentors in 14 (74%), principally due to
      lack of financial compensation and/or workload pressure. For five general
      practice nurses trained as health mentors, their roles had previously included
      some chronic disease management, but training enhanced their understanding and
      skills of self-management approaches and increased the focus on patient
      partnership, prioritising patients' choices and achievability. Difficulties that
      led to early withdrawal of health mentors were competing demands, insufficient
      time availability, phone calls having lower priority than face-to-face
      interactions and changing employment. Skills gained were rated as valuable,
      applicable to all clinical practice and transferable to other health care
      settings. Although these results suggest that training can enhance general
      practice nurses' skills to deliver self-management support in chronic disease,
      there are significant system barriers that need to be addressed through funding
      models and organisational change.

PMID- 22394667
TI  - Supporting chronic disease self-management: translating policies and principles
      into clinical practice.
AB  - To support self-management, health professionals need to adopt a client-centred
      approach and learn to deliver evidence-based behaviour change interventions. This
      paper reports on the evaluation of 1- and 2-day training programs developed to
      improve health professionals' capacity to support chronic disease self-management
      (CDSM). The 321 participants attended one of eighteen supporting CDSM courses
      held in urban and rural settings. Participants included nurses, allied health
      professionals, Aboriginal health workers and general practitioners. Data were
      collected at three time points: before participation; immediately after the
      training; and, for a sub-sample of 37 participants, 2 months after the training.
      Results revealed a significant and sustained increase in CDSM self-efficacy
      following training regardless of participants' gender, age or qualifications. A
      thematic analysis of the responses concerning intended practice revealed four
      main areas of intended practice change, namely: use behavioural strategies;
      improve communication with clients; adopt a client-centred approach; and improve
      goal setting. The number of practice changes at 2 months reported by a sub-sample
      of participants ranged from 1 to 20 with a mean of 14 (s.d.=4). The three most
      common areas of practice change point to the adoption by health professionals of
      a collaborative approach with chronic disease patients. Lack of staff trained in
      CDSM was seen as a major barrier to practice change, with lack of support and
      finance also named as barriers to practice change. Participants identified that
      increased training, support and awareness of the principles of supporting CDSM
      would help to overcome barriers to practice change. These results indicate a
      readiness among health professionals to adopt a more collaborative approach given
      the skills and the tools to put this approach into practice.

PMID- 22394668
TI  - High detection rate of significant prostate tumours in anterior zones using
      transperineal ultrasound-guided template saturation biopsy.
AB  - Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b. What's known
      on the subject? and What does the study add? Men with persistent suspicion for
      prostate cancer after previous negative standard transrectal biopsy series are
      offered saturation biopsy either transrectally or transperineally to increase
      cancer detection rate. A high-risk group of men with at least two previous
      negative transrectal biopsies underwent transperineal template-guided saturation
      biopsy. Prostate cancer was detected in 26%, predominantly in the anterior zones.
      PSA velocity or doubling time were the most powerful factors to predict cancer.
      OBJECTIVE: To evaluate the detection rate and the regional location of prostate
      cancer in men undergoing transperineal template-guided saturation biopsy (TTSB).
      PATIENTS AND METHODS: In all, 92 consecutive men with at least two previous
      negative transrectal biopsy series who underwent a multiple-core prostate TTSB at
      our centre were included in the study. * Univariable and multivariable logistic
      regression analyses were used to address the relationship between parameters
      before TTSB and prostate cancer-detection rate. * Covariates consisted of age at
      biopsy, free and total prostate-specific antigen (PSA), prostate volume, digital
      rectal examination findings, histological findings on previous biopsy, PSA
      velocity (PSAV), PSA-doubling time (PSADT) and the number of previous negative
      biopsy sets. RESULTS: Prostate cancer was diagnosed in 26% of the men. * A median
      of 30 cores was taken by TTSB. * Adenocarcinoma in >2 cores was detected in 58.5%
      and Gleason score >=7 was detected in 46% of the diagnosed men. * Most of the
      tumours (83.3%) were found in the anterior zones of the gland, with a
      significantly higher number of positive cores vs the posterior zones (mean 4.9 vs
      1.5, P= 0.015). * PSADT and PSAV were the only independent predictors of prostate
      cancer detection at multivariate analyses with odds ratios of 0.71 (P= 0.014) and
      1.58 (P= 0.025), respectively. CONCLUSIONS: TTSB has a high prostate cancer
      detection rate, especially in the anterior zones. * Men after at least two
      previous negative transrectal biopsy series and persistent suspicion of prostate
      cancer, as evidenced by rapid PSA dynamics, should be offered TTSB.

PMID- 22394669
TI  - Thyroid cancer in Ukraine after the Chernobyl accident (in the framework of the
      Ukraine-US Thyroid Project).
AB  - As a result of the accident at the Chernobyl Nuclear Power Plant, millions of
      residents of Belarus, Russia, and Ukraine were exposed to large doses of
      radioactive iodine isotopes, mainly I-131. The purpose of the Ukraine-American
      (UkrAm) and Belarus-American (BelAm) projects are to quantify the risks of
      thyroid cancer in the framework of a classical cohort study, comprising subjects
      who were aged under 18 years at the time of the accident, had direct measurements
      of thyroid I-131 radioactivity taken within two months after the accident, and
      were residents of three heavily contaminated northern regions of Ukraine
      (Zhitomir, Kiev, and Chernigov regions). Four two-year screening examination
      cycles were implemented from 1998 until 2007 to study the risks associated with
      thyroid cancer due to the iodine exposure caused during the Chernobyl accident. A
      standardised procedure of clinical examinations included: thyroid palpation,
      ultrasound examination, blood collection followed by a determination of thyroid
      hormone levels, urinary iodine content test, and fine-needle aspiration if
      required. Among the 110 cases of thyroid cancer diagnosed in UkrAm as the result
      of four screening examinations, 104 cases (94.5%) of papillary carcinomas, five
      cases (4.6%) of follicular carcinomas, and one case (0.9%) of medullary carcinoma
      were diagnosed.

PMID- 22394670
TI  - Some lessons on radiological protection learnt from the accident at the Fukushima
      Dai-ichi nuclear power plant.
AB  - The accident at the Fukushima Dai-ichi nuclear power plant released a large
      quantity of radioactive iodine and caesium into the environment. In terms of
      radiological protection, the evacuation and food restrictions that were adopted
      in a timely manner by the authorities effectively reduced the dose received by
      people living in the affected area. Since late March, the transition from an
      emergency to an existing exposure situation has been in progress. In selecting
      the reference exposure levels in some areas under an existing exposure situation,
      the authorities tried to follow the situation-based approach recommended by the
      ICRP. However, a mixture of emergency and post-emergency approaches confused the
      people living in the contaminated areas because the reactor conditions continued
      to be not completely stable. In deriving the criteria in an existing exposure
      situation, the regulatory authority selected 20 mSv y(-1). The mothers in the
      affected area believed that a dose of 20 mSv y(-1) was unacceptably high for
      children since 1 mSv y(-1) is the dose limit for the public under normal
      conditions. Internet information accelerated concern about the internal exposure
      to children and the related health effects. From some experiences after the
      accident the following lessons could be learned. The selection of reference doses
      in existing exposure situations after an accident must be openly communicated
      with the public using a risk-informed approach. The detriment-adjusted nominal
      risk coefficient was misused for calculating the hypothetical number of cancer
      deaths by some non-radiation experts. It would not be possible to resolve this
      problem unless the ICRP addressed an alternative risk assessment to convey the
      meaning and associated uncertainty of the risk to an exposed population. A
      situation-based approach in addition to a risk-informed approach needs to be
      disseminated properly in order to select the level of protection that would be
      the best possible under the prevailing circumstances. A dialogue between
      radiation and other risk experts such as those dealing with chemical exposures is
      now needed.

PMID- 22394671
TI  - The interfacial structure of water/protonated alpha-Al2O3 (11 20) as a function
      of pH.
AB  - Sum frequency vibrational spectroscopy (SFVS) was used to study the structure of
      the protonated alpha-Al(2)O(3) (11 20), and water/alpha-Al(2)O(3) (11 20)
      interfaces as a function of pH. By combining SFVS spectra with an oxygen
      terminated model suggested by x-ray reflectivity, we are able to understand
      several details of the protonated alpha-Al(2)O(3) (11 20) interface structure.
      For example, the spectral changes observed for the water/alpha-Al(2)O(3) (11 20)
      interface with varying pH could be accounted for by the protonation/deprotonation
      of particular surface hydroxyls. Our spectra also indicate that the point of zero
      charge for this interface is at pH ~ 6.7.

PMID- 22394672
TI  - Meanfield modeling of propofol-induced changes in spontaneous EEG rhythms.
AB  - During the maintenance period of propofol-induced general anesthesia, specific
      changes in spontaneous EEG rhythms can be observed. These comprise increased
      delta and theta power and the emergence of alpha oscillations over frontal
      regions. In this study we use a meanfield model of the thalamo-cortical system to
      reproduce these changes and to elucidate the underlying mechanisms. The model is
      able to reproduce the most dominant changes in the EEG and suggests that they are
      caused by the amplification of resonances within the thalamo-cortical system.
      Specifically, while observed increases in delta and alpha power are reflections
      of amplified resonances in the respective frequency bands, increases in theta
      power are caused indirectly by spectral power leakage from delta and alpha bands.
      The model suggests that these changes are brought about through increased
      inhibition within local cortical interneuron circuits. These results are
      encouraging and motivate more extensive use of neural meanfield models in
      elucidating the physiological mechanisms underlying the effects of
      pharmacological agents on macroscopic brain dynamics.

PMID- 22394673
TI  - Confounding of norm-based and adaptation effects in brain responses.
AB  - Separate neuroscience experiments have examined two properties of neural coding
      for perceptual stimuli. Adaptation studies seek a graded recovery from neural
      adaptation with ever greater dissimilarity between pairs of stimuli. Studies of
      prototype effects test for a larger absolute response to a stimulus which is
      distant from the center of a stimulus space. While intellectually distinct, these
      effects are confounded in measurement in standard neuroscience paradigms and can
      be mistaken for one another. Stimuli which are more distinctive are less subject
      to adaptation from perceptual neighbors. Therefore, a putative prototype effect
      may simply result from greater adaptation of prototypical stimuli by other
      stimuli in the experiment. Conversely, stimulus pairs which are the most
      perceptually distant from one another, and therefore expected to show the
      greatest recovery from adaptation, disproportionately draw from the extremes of
      the stimulus space. Thus, an apparent neural similarity effect may be created by
      an underlying prototype representation. We simulate BOLD fMRI results driven by
      each possible effect and demonstrate spurious results in support of the
      complementary effect. We then present an example fMRI experiment that
      demonstrates the confound and how it may be minimized. Finally, we discuss the
      implications of this intrinsic confound for studies of perceptual representation,
      neural coding, and category learning.

PMID- 22394674
TI  - Structural connectivity allows for multi-threading during rest: the structure of
      the cortex leads to efficient alternation between resting state exploratory
      behavior and default mode processing.
AB  - Despite the absence of stimulation or task conditions the cortex exhibits highly
      structured spatio-temporal activity patterns. These patterns are known as resting
      state networks (RSNs) and emerge as low-frequency fluctuations (<0.1 Hz) observed
      in the fMRI signal of human subjects during rest. We are interested in the
      relationship between structural connectivity of the cortex and the fluctuations
      exhibited during resting conditions. We are especially interested in the effect
      of degree of connectivity on resting state dynamics as the default mode network
      (DMN) is highly connected. We find in experimental resting fMRI data that the DMN
      is the functional network that is most frequently active and for the longest
      time. In large-scale computational simulations of the cortex based on the
      corresponding underlying DTI/DSI based neuroanatomical connectivity matrix, we
      additionally find a strong correlation between the mean degree of functional
      networks and the proportion of time they are active. By artificially modifying
      different types of neuroanatomical connectivity matrices in the model, we were
      able to demonstrate that only models based on structural connectivity containing
      hubs give rise to this relationship. We conclude that, during rest, the cortex
      alternates efficiently between explorations of its externally oriented functional
      repertoire and internally oriented processing as a consequence of the DMN's high
      degree of connectivity.

PMID- 22394675
TI  - Recent developments in our understanding of the antiphospholipid syndrome.
AB  - The antiphospholipid syndrome is an autoimmune disease that manifests clinically
      as recurrent thrombotic complications or foetal losses and serologically with
      elevated levels of antiphospholipid antibodies in the plasmas of these patients.
      The term 'antiphospholipid syndrome' is confusing, because the auto-antibodies
      are not directed against phospholipids but towards a plasma protein, beta(2) 
      glycoprotein I. For many years, the reason why auto-antibodies against beta(2) 
      glycoprotein I were pro-thrombotic was unclear, because beta(2) -glycoprotein I
      seems to be an obsolete protein in our circulation. Human and mice deficient in
      this protein do not express a clear phenotype. Recent studies on the structure
      and function of beta(2) -glycoprotein I have provided novel insights into the
      importance of this protein in physiology and its role in the pathology of the
      antiphospholipid syndrome.

PMID- 22394676
TI  - Friedreich's ataxia reveals a mechanism for coordinate regulation of oxidative
      metabolism via feedback inhibition of the SIRT3 deacetylase.
AB  - Friedreich's ataxia (FRDA) is the most common inherited human ataxia and is
      caused by a deficiency in the mitochondrial protein frataxin. Clinically,
      patients suffer from progressive spinocerebellar degeneration, diabetes and a
      fatal cardiomyopathy, associated with mitochondrial respiratory chain defects.
      Recent findings have shown that lysine acetylation regulates mitochondrial
      function and intermediary metabolism. However, little is known about lysine
      acetylation in the setting of pathologic energy stress and mitochondrial
      dysfunction. We tested the hypothesis that the respiratory chain defects in
      frataxin deficiency alter mitochondrial protein acetylation. Using two
      conditional mouse models of FRDA, we demonstrate marked hyperacetylation of
      numerous cardiac mitochondrial proteins. Importantly, this biochemical phenotype
      develops concurrently with cardiac hypertrophy and is caused by inhibition of the
      NAD(+)-dependent SIRT3 deacetylase. This inhibition is caused by an 85-fold
      decrease in mitochondrial NAD(+)/NADH and direct carbonyl group modification of
      SIRT3, and is reversed with excess SIRT3 and NAD(+) in vitro. We further
      demonstrate that protein hyperacetylation may be a common feature of
      mitochondrial disorders caused by respiratory chain defects, notably, cytochrome
      oxidase I (COI) deficiency. These findings suggest that SIRT3 inhibition and
      consequent protein hyperacetylation represents a negative feedback mechanism
      limiting mitochondrial oxidative pathways when respiratory metabolism is
      compromised, and thus, may contribute to the lethal cardiomyopathy in FRDA.

PMID- 22394677
TI  - Norrin stimulates cell proliferation in the superficial retinal vascular plexus
      and is pivotal for the recruitment of mural cells.
AB  - Mutations in Norrin, the ligand of a receptor complex consisting of FZD4, LRP5
      and TSPAN12, cause severe developmental blood vessel defects in the retina and
      progressive loss of the vascular system in the inner ear, which lead to
      congenital blindness and progressive hearing loss, respectively. We now examined
      molecular pathways involved in developmental retinal angiogenesis in a mouse
      model for Norrie disease. Comparison of morphometric parameters of the
      superficial retinal vascular plexus (SRVP), including the number of filopodia,
      vascular density and number of branch points together with inhibition of Notch
      signaling by using DAPT, suggest no direct link between Norrin and Notch
      signaling during formation of the SRVP. We noticed extensive vessel crossing
      within the SRVP, which might be a loss of Wnt- and MAP kinase-characteristic
      feature. In addition, endomucin was identified as a marker for central filopodia,
      which were aligned in a thorn-like fashion at P9 in Norrin knockout (Ndp(y/-))
      mice. We also observed elevated mural cell coverage in the SRVP of Ndp(y/-) mice
      and explain it by an altered expression of PDGFbeta and its receptor (PDGFRbeta).
      In vivo cell proliferation assays revealed a reduced proliferation rate of
      isolectin B4-positive cells in the SRVP from Ndp(y/-) mice at postnatal day 6 and
      a decreased mitogenic activity of mutant compared with the wild-type Norrin. Our
      results suggest that the delayed outgrowth of the SRVP and decreased angiogenic
      sprouting in Ndp(y/-) mice are direct effects of the reduced proliferation of
      endothelial cells from the SRVP.

PMID- 22394679
TI  - Tools for appraisal and revalidation--evaluation of regionally delivered
      workshops.
AB  - BACKGROUND: The advent of revalidation has created a need for occupational
      physicians to be provided with further advice on the preparation of their
      supporting information. A road show was delivered to the Society of Occupational
      Medicine (SOM) regional groups to meet the need. The objective of the road show
      was to improve delegates' confidence in the selection and development of
      supporting information for appraisal and revalidation by assembling a collection
      of tools. AIMS: To provide internal evaluation of the effectiveness of the road
      show. METHODS: The audience voting software Turning Point((r)) was used to gather
      delegates' responses to various questions on their opinion and confidence self
      rating. Data were then collated from all iterations. RESULTS: Eighty per cent of
      delegates became more confident in the selection and development of supporting
      information for appraisal and revalidation, with the improvement in rating scores
      being highly significant (P < 0.001). The importance of audit and the use of self
      reflective were emphasized. CONCLUSIONS: Internal validation using Turning
      Point((r)) was most useful. This was the first time that the SOM had used a road
      show format to deliver an educational topic. The road show format was successful,
      and other similar topics would benefit from a similar delivery.

PMID- 22394678
TI  - Imprinting control region (ICR) of the Peg3 domain.
AB  - The imprinting and transcription of the 500 kb genomic region surrounding the
      mouse Peg3 is predicted to be regulated by the Peg3-differentially methylated
      region (DMR). In the current study, this prediction was tested using a mutant
      mouse line lacking this potential imprinting control region (ICR). At the
      organismal level, paternal and maternal transmission of this knockout (KO) allele
      caused either reduced or increased growth rates in the mouse, respectively. In
      terms of the imprinting control, the paternal transmission of the KO allele
      resulted in bi-allelic expression of the normally maternally expressed Zim2,
      whereas the maternal transmission switched the transcriptionally dominant allele
      for Zfp264 (paternal to maternal). However, the allele-specific DNA methylation
      patterns of the DMRs of Peg3, Zim2 and Zim3 were not affected in the mice that
      inherited the KO allele either paternally or maternally. In terms of the
      transcriptional control, the paternal transmission caused a dramatic down
      regulation in Peg3 expression, but overall up-regulation in the other nearby
      imprinted genes. Taken together, deletion of the Peg3-DMR caused global changes
      in the imprinting and transcription of the Peg3 domain, confirming that the Peg3
      DMR is an ICR for this imprinted domain.

PMID- 22394680
TI  - Exposure to psychosocial work factors in 31 European countries.
AB  - BACKGROUND: Although psychosocial work factors are recognized as major
      occupational risk factors, little information is available regarding the
      prevalence of exposure to these factors and the differences in exposure between
      countries. AIMS: To explore the differences in various psychosocial work
      exposures between 31 European countries. METHODS: The study was based on a sample
      of 14,881 male and 14,799 female workers from the 2005 European Working
      Conditions Survey. Eighteen psychosocial work factors were studied: low decision
      latitude (skill discretion and decision authority), high psychological demands,
      job strain, low social support, iso-strain, physical violence, sexual harassment,
      bullying, discrimination, work-family imbalance, long working hours, high effort,
      job insecurity, low job promotion, low reward and effort-reward imbalance.
      Covariates were age, number of workers in household, occupation, economic
      activity, self-employed/employee, public/private sector and part/full time work.
      Statistical analysis was performed using multilevel logistic regression analysis.
      RESULTS: Significant differences in all psychosocial work factors were observed
      between countries. The rank of the countries varied according to the exposure
      considered. However, some countries, especially Denmark, Netherlands and Norway,
      displayed a significantly lower prevalence of exposure to four factors or more,
      while some Southern and Eastern countries, especially Czech Republic, Greece,
      Lithuania and Turkey, had a higher prevalence. CONCLUSIONS: Differences in
      psychosocial work exposures were found between countries. This study is the first
      to compare a large set of psychosocial work exposures between 31 European
      countries. These findings may be useful to guide prevention policies at European
      level.

PMID- 22394681
TI  - Prospective relationships between workplace sexual harassment and psychological
      distress.
AB  - BACKGROUND: Exposure to workplace sexual harassment (SH) has been associated with
      impaired mental health, but longitudinal studies confirming the relationship are
      lacking. AIMS: To examine gender differences in prospective associations between
      SH and psychological distress. METHODS: Baseline questionnaire survey data were
      collected in 2005 in a representative sample of Norwegian employees. Follow-up
      data were collected in 2007. SH was measured with the Bergen Sexual Harassment
      Scale. Psychological distress was measured with the 25 item Hopkins Symptom
      Checklist (HSCL-25) with cases of psychological distress defined as having a mean
      score of <1.75. Variables were measured at both baseline and follow-up. Logistic
      regression analysis was used to analyse data. RESULTS: Response rates were 57% in
      2005 and 75% in 2007 when the final cohort comprised 1775 respondents. After
      adjusting for baseline distress and age, exposure to SH at baseline was
      associated with psychological distress at follow-up among women [odds ratio (OR):
      2.03; 95% confidence interval (CI): 1.2-3.39] but not men (OR: 1.32; 95% CI: 0.72
      2.43). Baseline distress was significantly related to SH at follow-up among men
      (OR: 3.03; 95% CI: 1.74-5.26) but not women (OR: 1.15; 95% CI: 0.69-1.92).
      CONCLUSIONS: The study found that SH contributed to subsequent psychological
      distress among women. Workplace measures against SH would be expected to lead to
      a reduction in mental disorders. The finding that psychological distress predicts
      SH among men may indicate either a vulnerability factor or a negative perception
      mechanism.

PMID- 22394682
TI  - The HSE indicator tool, psychological distress and work ability.
AB  - BACKGROUND: The Health and Safety Executive (HSE) indicator tool is one of the
      most commonly used tools for assessing the risk of work-related stress. Few
      studies, however, have investigated whether and how its scales are related to
      psychological distress or other work-related health outcomes. AIMS: To
      investigate the relationship between the HSE indicator tool, psychological
      distress, as measured by the General Health Questionnaire (GHQ)-12, and work
      ability, assessed by the Work Ability Index (WAI). METHODS: All the employees of
      a mid-sized bank in Italy were asked to fill in an anonymous cross-sectional
      questionnaire. The questionnaire was structured in four sections: the first one
      comprised socio-demographic questions and the other three corresponded,
      respectively, to the Italian translations of the GHQ-12, the HSE and the WAI
      questionnaires. RESULTS: Four hundred and thirteen employees completed the
      questionnaire. The response rate was 99%. Controlling for age and gender, the
      indicator subscales were negatively associated with the adopted measures of
      psychological distress and work ability. The GHQ score was also highly correlated
      with the WAI score and able to explain ~ 47% of its variance. The only subscale
      that was still significantly associated with the WAI after removing the effect of
      psychological distress was 'control'. CONCLUSIONS: The study presents new
      evidence for the validity of the HSE indicator tool to estimate the risk of work
      related stress and suggests that most but not all the effects of psychosocial
      conditions on work ability might be mediated by the level of psychological
      distress induced by these conditions.

PMID- 22394683
TI  - The effect of underlying clinical conditions on the risk of developing invasive
      pneumococcal disease in England.
AB  - OBJECTIVE: To inform national policy making on the use of the 13-valent
      pneumococcal vaccine among risk groups we estimated the increased risk of
      invasive pneumococcal disease (IPD) outcomes among clinical risk groups. Three
      years of post 7-valent pneumococcal conjugate vaccine (PCV7) data was included to
      investigate the herd protection effects. METHODS: Over 22,000 IPD patients in
      England (March 2002-March 2009 - aged 2 and over) were linked to their
      hospitalisation records. The prevalence of risk factors in these patients was
      compared to the prevalence of risk factors in the general population. RESULTS:
      There was an increased odds ratio (OR) for hospitalisation (OR 11.7 2-15 years;
      7.6 16-64; 2.7 65+) and death (OR 2.4 2-15 years, 3.9 16-64, 1.2 65+) from IPD
      among risk group. The most important risk factors that predict IPD are chronic
      liver disease, immunosuppression, and chronic respiratory diseases. Herd
      protection effects due to introduction of the 7-valent vaccine were identical in
      both patient groups as shown by the similar decline in the proportion of IPD
      caused by PCV7 serotypes in risk and non-risk groups. CONCLUSIONS: There is a
      marked increased risk of IPD among those with certain clinical conditions,
      suggesting potential benefit from a targeted vaccination approach. However, the
      indirect protection from conjugate vaccination of children suggests PCV
      vaccination of high-risk groups may not provide substantial additional benefit
      once herd immunity takes effect.

PMID- 22394684
TI  - Protein tyrosine phosphatase Meg2 dephosphorylates signal transducer and
      activator of transcription 3 and suppresses tumor growth in breast cancer.
AB  - INTRODUCTION: Signal transducer and activator of transcription 3 (STAT3) is over
      activated or phosphorylated in breast cancers. The hyper-phosphorylation of STAT3
      was attributed to either up-regulated phosphorylation by several tyrosine-kinases
      or down-regulated activity of phosphatases. Although several factors have been
      identified to phosphorylate STAT3, it remains unclear how STAT3 is
      dephosphorylated by PTPMeg2. The aim of this study was to determine the role of
      PTPMeg2 as a phosphatase in regulation of the activity of STAT3 in breast
      cancers. METHODS: Immunoprecipitation assays were used to study the interaction
      of STAT3 with PTPMeg2. A series of biochemistry experiments were performed to
      evaluate the role of PTPMeg2 in the dephosphorylation of STAT3. Two breast cancer
      cell lines MCF7 (PTPMeg2 was depleted as it was endogenously high) and MDA-MB-231
      (PTPMeg2 was overexpressed as it was endogenously low) were used to compare the
      level of phosphorylated STAT3 and the tumor growth ability in vitro and in vivo.
      Samples from breast carcinoma (n = 73) were subjected to a pair-wise Pearson
      correlation analysis for the correlation of levels of PTPMeg2 and phosphorylated
      STAT3. RESULTS: PTPMeg2 directly interacts with STAT3 and mediates its
      dephosphorylation in the cytoplasm. Over-expression of PTPMeg2 decreased tyrosine
      phosphorylation of STAT3 while depletion of PTPMeg2 increased its
      phosphorylation. The decreased tyrosine phosphorylation of STAT3 is coupled with
      suppression of STAT3 transcriptional activity and reduced tumor growth in vitro
      and in vivo. Levels of PTPMeg2 and phosphorylated STAT3 were inversely correlated
      in breast cancer tissues (P = 0.004). CONCLUSIONS: PTPMeg2 is an important
      phosphatase for the dephosphorylation of STAT3 and plays a critical role in
      breast cancer development.

PMID- 22394686
TI  - The identification of job opportunities for severely disabled sick-listed
      employees.
AB  - BACKGROUND: Work disability is a major problem for both the worker and society.
      To explore the work opportunities in regular jobs of persons low in functional
      abilities, we tried to identify occupations low in task demands. Because of the
      variety of functional abilities and of the corresponding work demands, the
      disabled persons need to be classified by type of disability in a limited number
      of subgroups. Within each subgroup, occupations judged suitable for the most
      seriously disabled will be selected as having a very low level of the
      corresponding task demands. These occupations can be applied as reference
      occupations to assess the presence or absence of work capacity of sick-listed
      employees in regular jobs, and as job opportunities for people with a specific
      type of functional disability. METHODS: Registered data from 50,931 disability
      assessments within the Dutch social security system were used in a second order
      factor analysis to identify types of disabilities in claimants for a disability
      pension. Threshold values were chosen to classify claimants according to the
      severity of the disability. In the disability assessment procedure, a labour
      expert needs to select jobs with task demands not exceeding the functional
      abilities of the claimant. For each type of disability, the accessible jobs for
      the subgroup of the most severely disabled claimants were identified as lowest in
      the corresponding demand. RESULTS: The factor analysis resulted in four types of
      disabilities: general physical ability; autonomy; psychological ability; and
      manual skills. For each of these types of disablement, a set of four to six
      occupations low in task demands were selected for the subgroup of most severely
      disabled claimants. Because of an overlap of the sets of occupations, 13
      occupations were selected in total. The percentage of claimants with at least one
      of the occupations of the corresponding set (the coverage), ranged from 84% to
      93%. An alternative selection of six occupations for all subgroups with even less
      overlap had a coverage ranging from 84% to 89% per subgroup. CONCLUSION: This
      study resulted in two proposals for a set of reference occupations. Further
      research will be needed to compare the results of the new method of disability
      assessment to the results of the method presently used in practice.

PMID- 22394687
TI  - Association of changes in the use of board-certified critical care intensivists
      with mortality outcomes for trauma patients at a well-established level I urban
      trauma center.
AB  - BACKGROUND: An intensivist-directed Intensive Care Unit is a closed-model unit in
      which a physician formally trained in critical care plays a leadership role in
      patient management. In the last decade, there has been a move toward closed
      Intensive Care Units. The purpose of this evaluation was to assess the
      association of changes in the use of intensivists to a closed-model with
      mortality outcomes in injured patients seen in a long-established urban Level I
      Trauma Center. METHODS: This analysis used data from the Scottsdale Healthcare
      Osborn Medical Center trauma registry from January 1, 2002-December 31, 2008.
      Mortality prior to hospital discharge was compared in the pre-intensivist
      (intensivists were not employed and did not provide care), partial intensivist
      (intensivists were employed and provided care during some Intensive Care Unit
      shifts) and full-time intensivist (intensivists were employed and provided care
      in the Intensive Care Unit full time) periods. Multiple logistic regression
      analysis was used to estimate odds ratios for mortality adjusting for patient
      characteristics and injury severity for the partial intensivist and full-time
      intensivist periods compared with the pre-intensivist period. RESULTS: Of 18,918
      patients, 365 (1.9%) died before hospital discharge. After adjustment for
      demographic factors and injury severity score, for all patients, odds ratios
      comparing the partial intensivist and full-intensivist periods with the pre
      intensivist period were 0.84 (95% confidence interval 0.64-1.11) and 0.99 (95%
      confidence interval 0.69-1.41). In patients with an injury severity score 16-24,
      the adjusted OR for death was 0.20 (95% CI 0.07-0.58) comparing the partial
      intensivist with the pre-intensivist period and 0.30 (95% CI 0.11-0.88) comparing
      the full-time intensivist period with the pre-intensivist period. For patients
      age 65 + years, compared with the pre-intensivist period, odds ratio were 0.51
      (95% confidence interval 0.31-0.84) and 0.61 (95% confidence interval 0.32-1.16)
      for the partial and full-time intensivist periods respectively. CONCLUSIONS: In
      our setting, a change to a closed Intensive Care Unit model was associated with
      improved mortality outcomes in patients with less severe injuries and patients
      age 65+ years.

PMID- 22394685
TI  - The resistance of intracellular mediators to doxorubicin and cisplatin are
      distinct in 3D and 2D endometrial cancer.
AB  - BACKGROUND: Advanced endometrial cancer often shows resistance to clinical
      chemotherapy although potencies of anticancer drugs in vitro are promising. The
      disparity suggests that in vivo microenvironments are not recapitulated by in
      vitro models used for preclinical testing. However, spheroids replicate some
      important properties of tumours in vivo. Therefore, for the first time, we
      compared effects of doxorubicin and cisplatin on 3D multicellular structures and
      2D cell monolayers of endometrial cancer cells. METHODS: 3D multicellular
      structures were generated by culturing cancer cells on non-adherent surfaces; and
      for comparison cell monolayers were cultured on adherent culture plates.
      Ishikawa, RL95-2, and KLE cell lines were studied. Morphologies of 3D
      multicellular structures were examined. After 48 hours treatment with anticancer
      drugs, apoptosis, proliferation, glucose metabolism and vascular endothelial
      growth factor (VEGF) were analysed. Immunostaining of PCNA, Glut-1, p-Erk1/2, SOD
      1 and p-Akt1/2/3 was also performed. RESULTS: Distinct 3D multicellular
      morphologies were formed by three different endometrial cancer cell lines.
      Doxorubicin induced less apoptosis in 3D multicellular structures of high grade
      cancer cells (RL95-2 and KLE cell lines) than in cell monolayers. Parallel
      alterations in Erk1/2 phosphorylation and cell proliferation might suggest they
      were linked and again doxorubicin had less effect on 3D multicellular structures
      than cell monolayers. On the other hand, there was no correlation between altered
      glucose metabolism and proliferation. The responses depended on cancer cell lines
      and were apparently not mediated by altered Glut-1 levels. The level of SOD-1 was
      high in 3D cell cultures. The effects on VEGF secretion were various and cancer
      cell line dependent. Importantly, both doxorubicin and cisplatin had selective
      paradoxical stimulatory effects on VEGF secretion. The microenvironment within 3D
      multicellular structures sustained Akt phosphorylation, consistent with it having
      a role in anchorage-independent pathways. CONCLUSIONS: The cancer cells responded
      to microenvironments in a distinctive manner. 3D multicellular structures
      exhibited greater resistance to the agents than 2D monolayers, and the
      differences between the culture formats were dependent on cancer cell lines. The
      effects of anticancer drugs on the intracellular mediators were not similar in 3D
      and 2D cultures. Therefore, using 3D cell models may have a significant impact on
      conclusions derived from screening drugs for endometrial carcinomas.

PMID- 22394688
TI  - Differential role of CB1 and TRPV1 receptors on anandamide modulation of
      defensive responses induced by nitric oxide in the dorsolateral periaqueductal
      gray.
AB  - CB1, TRPV1 and NO can regulate glutamate release and modify defensive behaviors
      in regions related to defensive behavior such as the dorsolateral periaqueductal
      gray (dlPAG). A possible interaction between the endocannabinoid and nitrergic
      systems in this area, however, has not been investigated yet. The objective of
      the present work was to verify if activation of CB1 or TRPV1 receptors could
      interfere in the flight responses induced in rats by the injection of SIN-1, an
      NO donor, into the dlPAG. The results showed that local administration of a low
      dose (5 pmol) of anandamide (AEA) attenuated the flight responses, measured by
      the total distance moved and maximum speed in an open arena, induced by intra
      dlPAG microinjection of SIN-1 (150 nmol). URB597 (0.1 nmol), an inhibitor of
      anandamide metabolism, produced similar effects. When animals were locally
      treated with the CB1 receptor antagonist AM251 the effective AEA dose (5 pmol)
      increased, rather than decreased, the flight reactions induced by SIN1-1. Higher
      (50-200 nmol) doses of AEA were ineffective and even tended to potentiate the SIN
      1 effect. The TRPV1 antagonist capsazepine (CPZ, 30 nmol) prevented SIN-1 effects
      and attenuated the potentiation of its effect by the higher (200 nmol) AEA dose.
      The results indicate that AEA can modulate in a dual way the pro-aversive effects
      of NO in the dlPAG by activating CB1 or TRPV1 receptors.

PMID- 22394689
TI  - A modular neural model of motor synergies.
AB  - Animals such as reptiles, amphibians and mammals (including humans) are
      mechanically extremely complex. It has been estimated that the human body has
      between 500 and 1400 degrees of freedom! And yet, these animals can generate an
      infinite variety of very precise, complicated and goal-directed movements in
      continuously changing and uncertain environments. Understanding how this is
      achieved is of great interest to both biologists and engineers. There are
      essentially two questions that must be addressed: (1) What type of control
      strategy is used to handle the large number of degrees of freedom involved? and
      (2) How is this strategy instantiated in the substrate of neural and
      musculoskeletal elements comprising the animal bodies? The first question has
      been studied intensively for several decades, providing strong indications that,
      rather than using standard feedback control based on continuous tracking of
      desired trajectories, animals' movements emerge from the controlled combination
      of pre-configured movement primitives or synergies. These synergies represent
      coordinated activity patterns over groups of muscles, and can be triggered as a
      whole with controlled amplitude and temporal offset. Complex movements can thus
      be constructed from the appropriate combination of a relatively small number of
      synergies, greatly simplifying the control problem. Although experimental studies
      on animal movements have confirmed the existence of motor synergies, and their
      utility has been demonstrated in the control of fairly complex robots, their
      neural basis remains poorly understood. In this paper, we introduce a simple but
      plausible and general neural model for motor synergies based on the principle
      that these functional modules reflect the structural modularity of the underlying
      physical system. Using this model, we show that a small set of synergies selected
      through a redundancy-reduction principle can generate a rich motor repertoire in
      a model two-jointed arm system. We investigate the synergies generated by this
      model systematically with respect to various parameters, and compare them to
      those observed in experiments.

PMID- 22394690
TI  - Man vs. computer: benchmarking machine learning algorithms for traffic sign
      recognition.
AB  - Traffic signs are characterized by a wide variability in their visual appearance
      in real-world environments. For example, changes of illumination, varying weather
      conditions and partial occlusions impact the perception of road signs. In
      practice, a large number of different sign classes needs to be recognized with
      very high accuracy. Traffic signs have been designed to be easily readable for
      humans, who perform very well at this task. For computer systems, however,
      classifying traffic signs still seems to pose a challenging pattern recognition
      problem. Both image processing and machine learning algorithms are continuously
      refined to improve on this task. But little systematic comparison of such systems
      exist. What is the status quo? Do today's algorithms reach human performance? For
      assessing the performance of state-of-the-art machine learning algorithms, we
      present a publicly available traffic sign dataset with more than 50,000 images of
      German road signs in 43 classes. The data was considered in the second stage of
      the German Traffic Sign Recognition Benchmark held at IJCNN 2011. The results of
      this competition are reported and the best-performing algorithms are briefly
      described. Convolutional neural networks (CNNs) showed particularly high
      classification accuracies in the competition. We measured the performance of
      human subjects on the same data-and the CNNs outperformed the human test persons.

PMID- 22394691
TI  - Strain relief and disorder in commensurate water layers formed on Pd(111).
AB  - Water adsorbs and desorbs intact on Pd(111), forming a hydrogen-bonded wetting
      layer whose structure we examine by low energy electron diffraction (LEED) and He
      atom scattering (HAS). LEED shows that water forms commensurate (?3 * ?3)R30
      degrees  clusters that aggregate into a partially ordered, approximately (7 * 7)
      superstructure as the layer completes. HAS indicates that the water layer remains
      disordered on a local (approximately 10 A) scale. Based on workfunction
      measurements and density functional theory simulations we propose that water
      forms small, flat domains of a commensurate (?3 * ?3)R30 degrees  water network,
      separated by disordered domain boundaries containing largely H-down water. This
      arrangement allows the water layer to adapt its density and relieve the lateral
      strain associated with adsorbing water in the optimum flat atop adsorption site.
      We discuss different possibilities for the structure of these domain walls and
      compare this strain relief mechanism to the highly ordered, large unit cell
      structures formed on surfaces such as Pt(111).

PMID- 22394692
TI  - Neuroprotective effects of VEGF administration after focal cerebral
      ischemia/reperfusion: dose response and time window.
AB  - Administration of vascular endothelial growth factor (VEGF) has been shown to
      increase cerebral blood flow and reduce neurological damage after experimental
      ischemic brain injury. The purpose of this study was to examine the optimal dose
      and time window for the neuroprotective effect of VEGF when administrated after
      focal ischemia/reperfusion injury in rabbits. Focal cerebral ischemia/reperfusion
      was induced by the middle cerebral artery occlusion (MCAO) method. In a dose
      response experiment, low (1.25 ng/MUL), middle (2.5 ng/MUL) and high (5.0 ng/MUL)
      doses of VEGF were administered 2h after MCAO by the route of perifocal region.
      The VEGF at a dose of middle (2.5 ng/MUL) displayed excellent effects on
      neuroprotective efficacy for focal cerebral ischemia/reperfusion injury. In
      another experiment, 2.5 ng/MUL VEGF was administered at times varying from 2 to
      8h after MCAO. Infarct volume, water content and neurological deficits were
      significantly reduced when VEGF was given at 2 and 3h after injury. The
      protective effect was less when the same dose was given at the later times. Thus,
      the present findings indicated that VEGF reduced ischemic neuronal danger with a
      therapeutic time window within the first 3h of transient MCAO and may be useful
      in the treatment of acute ischemic stroke in humans.

PMID- 22394694
TI  - Mental health consequences of the Chernobyl disaster.
AB  - The psychosocial consequences of disasters have been studied for more than 100
      years. The most common mental health consequences are depression, anxiety, post
      traumatic stress disorder, medically unexplained somatic symptoms, and stigma.
      The excess morbidity rate of psychiatric disorders in the first year after a
      disaster is in the order of 20%. Disasters involving radiation are particularly
      pernicious because the exposure is invisible and universally dreaded, and can
      pose a long-term threat to health. After the Chernobyl disaster, studies of clean
      up workers (liquidators) and adults from contaminated areas found a two-fold
      increase in post-traumatic stress and other mood and anxiety disorders and
      significantly poorer subjective ratings of health. Among liquidators, the most
      important risk factor was severity of exposure. In general population samples,
      the major risk factor was perceived exposure to harmful levels of radiation.
      These findings are consistent with results from A-bomb survivors and populations
      studied after the Three Mile Island nuclear power plant accident. With regard to
      children, apart from findings from ecological studies that lack direct data on
      radiation or other teratologic exposures and local studies in Kiev, the
      epidemiologic evidence suggests that neither radiation exposure nor the stress of
      growing up in the shadow of the accident was associated with emotional disorders,
      cognitive dysfunction, or impaired academic performance. Thus, based on the
      studies of adults, the Chernobyl Forum concluded that mental health was the
      largest public health problem unleashed by the accident. Since mental health is a
      leading cause of disability, physical morbidity, and mortality, health monitoring
      after radiation accidents like Fukushima should include standard measures of well
      being. Moreover, given the comorbidity of mental and physical health, the
      findings support the value of training non-psychiatrist physicians in recognizing
      and treating common mental health problems like depression in Fukushima patients.

PMID- 22394693
TI  - Evaluation of a health promotion program in children: Study protocol and design
      of the cluster-randomized Baden-Wurttemberg primary school study [DRKS-ID:
      DRKS00000494].
AB  - BACKGROUND: Increasing prevalences of overweight and obesity in children are
      known problems in industrialized countries. Early prevention is important as
      overweight and obesity persist over time and are related with health problems
      later in adulthood. "Komm mit in das gesunde Boot - Grundschule" is a school
      based program to promote a healthier lifestyle. Main goals of the intervention
      are to increase physical activity, decrease the consumption of sugar-sweetened
      beverages, and to decrease time spent sedentary by promoting active choices for
      healthy lifestyle. The program to date is distributed by 34 project delivery
      consultants in the state of Baden-Wurttemberg and is currently implemented in 427
      primary schools. The efficacy of this large scale intervention is examined via
      the Baden-Wurttemberg Study. METHODS/DESIGN: The Baden-Wurttemberg Study is a
      prospective, stratified, cluster-randomized, and longitudinal study with two
      groups (intervention group and control group). Measurements were taken at the
      beginning of the academic years 2010/2011 and 2011/2012. Efficacy of the
      intervention is being assessed using three main outcomes: changes in waist
      circumference, skinfold thickness and 6 minutes run. Stratified cluster
      randomization (according to class grade level) was performed for primary schools;
      pupils, teachers/principals, and parents were investigated. An approximately
      balanced number of classes in intervention group and control group could be
      reached by stratified randomization and was maintained at follow-up. DISCUSSION:
      At present, "Komm mit in das Gesunde Boot - Grundschule" is the largest school
      based health promotion program in Germany. Comparative objective main outcomes
      are used for the evaluation of efficacy. Simulations showed sufficient power with
      the existing sample size. Therefore, the results will show whether the promotion
      of a healthier lifestyle in primary school children is possible using a
      relatively low effort within a school-based program involving children, teachers
      and parents. The research team anticipates that not only efficacy will be proven
      in this study but also expects many other positive effects of the program. TRIAL
      REGISTRATION: German Clinical Trials Register (DRKS), DRKS-ID: DRKS00000494.

PMID- 22394695
TI  - Abdominal counter pressure in CPR: what about the lungs? An in silico study.
AB  - The external pumping action in CPR should generate sufficient flow and pressure,
      but the pump must also be 'primed' by ongoing venous return. Different additions
      to standard CPR are in use just for this purpose. Active decompression of the
      thorax (ACD-CPR) to 'suck in' venous blood has proven successful, but,
      theoretically, compression of venous reservoirs in the abdomen should be even
      more effective. We compared different techniques for improved CPR with specific
      attention to the pulmonary circulation. We did our comparisons 'in silico' rather
      than 'in vivo' in a well-evaluated computer model. METHODS: We used an adapted
      version of Babb's computer model for CPR, reprogrammed in Matlab((r)). (1) We
      compared standard chest compression-only CPR (CO-CPR) and ACD-CPR to CPR with
      interposed abdominal compression (IAC-CPR). (2) Since the thorax/heart
      configuration differs between patients, and consequently the way blood is
      propelled by the chest compressions, we checked the influence of the ratio
      thoracic/cardiac pump effectiveness. RESULTS: (1) Only IAC-CPR leads to
      physiological values for mean aortic pressure and cardiac output. (2) However,
      since the whole heart is in the pressure chamber of the compressed thorax,
      pulmonary artery pressure rises to about the same level as aortic pressure. In
      practice, this might lead to pulmonary edema during and after CPR, unless (3)
      intra-abdominal compression pressure is strictly limited; simulations indicate
      that intra-abdominal pressure should not exceed 30-40 mmHg. CONCLUSIONS: IAC-CPR
      outperforms the other techniques in achieving good aortic pressure and cardiac
      output. However, abdominal pressure should be limited.

PMID- 22394696
TI  - Complication of intraosseous administration of systemic fibrinolysis for a
      massive pulmonary embolism with cardiac arrest.

PMID- 22394697
TI  - Preparation and characterization of biomimetic silk fibroin/chitosan composite
      nanofibers by electrospinning for osteoblasts culture.
AB  - In this study, we have successfully fabricated electrospun bead-free silk
      fibroin [SF]/chitosan [CS] composite nanofibers [NFs] covering the whole range of
      CS content (0%, 25%, 50%, 75%, and 100%). SF/CS spinning solutions were prepared
      in a mixed solvent system of trifluoroacetic acid [TFA] and dichloromethane. The
      morphology of the NFs was observed by scanning electron microscope, and the
      average fiber diameter ranges from 215 to 478 nm. Confocal laser scanning
      microscopy confirms the uniform distribution of SF and CS within the composite
      NFs. To increase biocompatibility and preserve nanostructure when seeded with
      cells in culture medium, NFs were treated with an ethanol/ammonia aqueous
      solution to remove residual TFA and to change SF protein conformation. After the
      chemical treatment, SF/CS NFs could maintain the original structure for up to 54
      days in culture medium. Properties of pristine and chemically treated SF/CS NFs
      were investigated by Fourier transform infrared spectroscopy [FT-IR], X-ray
      diffraction [XRD], and thermogravimetry/differential scanning calorimetry
      [TG/DSC]. Shift of absorption peaks in FT-IR spectra confirms the conformation
      change of SF from random coil to beta-sheet by the action of ethanol, which is
      also consistent with the SF crystalline diffraction patterns measured by XRD.
      From TG/DSC analysis, the decomposition temperature peaks due to salt formation
      from TFA and protonated amines disappeared after chemical treatment, indicating
      complete removal of TFA by binding with ammonium ions during the treatment. This
      was also confirmed with the disappearance of F1s peak in X-ray photoelectron
      spectroscopy spectra and disappearance of TFA salt peaks in FT-IR spectra. The
      composite NFs could support the growth and osteogenic differentiation of human
      fetal osteoblastic [hFOB] cells, but each component in the composite NF shows
      distinct effect on cell behavior. SF promotes hFOB proliferation while CS
      enhances hFOB differentiation. The composite SF/CS NFs will be suitable for bone
      tissue engineering applications by choosing a suitable blend composition.PACS:
      87.85.jf; 87.85.Rs; 68.37.Hk.

PMID- 22394698
TI  - Current status of childhood obesity and its associated morbidities in Turkey.
AB  - As a transitional society, rapid changes have occurred in the social, economic,
      nutritional and lifestyle aspects of the Turkish population over the last three
      decades. As a result, the prevalence of overweight and obesity has shown a
      dramatic increase in the adult Turkish population, reaching figures as high as 30
      40%. Although there is no nationwide figure regarding the prevalence of
      overweight and obesity in Turkish children and adolescents, several local studies
      performed between 2000 and 2010 in different regions of the country have
      demonstrated varying prevalence rates of 10.3%-17.6% and 1.9%-7.8% for overweight
      and obesity, respectively, in children aged 6-16 years. The differences in the
      figures obtained in these regions are thought to be due to variations in the
      subject sampling. The figures appear to vary depending on residential (urban vs.
      rural) and economic conditions. Belonging to a high-income family, living in a
      large city, having obese parents, being of high birth weight, consuming sugar
      sweetened beverages (soft drinks, juice drinks, etc.), and spending time in front
      of TV and PC were identified as the most common risk factors. Complications and 
      co-morbidities of obesity have also started to appear in our pediatric
      population. Metabolic syndrome, diagnosed according to the International Diabetes
      Federation criteria, was found in 2.3% of Turkish schoolchildren aged 10-19
      years. This rate was 28% in obese children. Preventive public measures have
      started to be implemented by the State and other bodies to control the rising
      trends in obesity.

PMID- 22394700
TI  - Height, weight and body mass index percentiles of children aged 6-14 years living
      at moderate altitudes.
AB  - OBJECTIVE: Individuals living at high altitudes are reported to have lower
      stature and also a smaller chest size in relation to their stature. Altitude
      related hypobaric hypoxia is considered to be the major cause of these
      alterations in growth, but adverse socioeconomic and/or other environmental
      conditions may also have a role in poor growth performance. This study was
      undertaken to provide growth data on children and adolescents living in a
      moderate-altitude area in Turkey. METHODS: The dataset of an anthropometric study
      conducted among a population living in a city at an altitude of 2000 meters was
      analyzed. A total of 1638 children and adolescents (871 males and 767 females)
      aged between 6 and 14 years were included in this study. The LMS method was used
      in the analysis and percentile values corresponding to the 3rd, 5th, 10th, 15th,
      25th, 50th, 75th, 85th, 90th, 95th and 97th percentiles for height, weight and
      body mass index (BMI) were estimated. The results were compared with the
      measurements of children and adolescents living in areas of lower altitude in
      Turkey. RESULTS: Starting at ages 0-10 years, height, weight and BMI values of
      children and adolescents of both genders living at an altitude of 2000 meters
      were noticeably lower than those reported for their counterparts living in areas
      of lower altitude in Turkey. CONCLUSIONS: The higher values for height, weight
      and BMI in children living in low-altitude areas can be attributed to altitude
      effect, but socioeconomic and microclimate effects cannot be discarded and
      further studies are needed.

PMID- 22394699
TI  - Association between apolipoprotein E polymorphism and subclinic atherosclerosis
      in patients with type 1 diabetes mellitus.
AB  - OBJECTIVE: The most important cause of morbidity and mortality in type 1 diabetes
      mellitus (DM) is atherosclerosis. Apolipoprotein E (Apo E) polymorphism is
      accused of being the genetic risk factor for atherosclerosis. The aim of the
      present study was to determine which Apo E polymorphism was related to
      atherosclerosis in patients with type 1 DM. METHODS: Seventy-four patients with
      type 1 DM were enrolled in the study. Age, diabetes duration, daily insulin dose,
      microalbuminuria, and major cardiovascular risk factors including anthropometric
      and metabolic parameters were assessed in each patient. Non-invasive
      ultrasonographic measurements were also performed. For determination of Apo E
      genotype, DNA was extracted from venous blood from all subjects using standard
      methods. Apo E genotyping was performed using a PCR-restriction fragment-length
      polymorphism assay. RESULTS: Systolic blood pressure and carotid artery intima
      media thickness (CA-IMT) were increased in subjects with E4/E4 polymorphism.
      According to univariate analysis, when adjusted for all risk factors, genotypes
      did not differ for total cholesterol, high-density lipoprotein cholesterol, low
      density lipoprotein cholesterol and triglycerides (p>0.05). However, E3/E3, E3/E4
      and E4/E4 genotypes were found to be associated with an increase in CA-IMT
      (p<0.001). CONCLUSIONS: Our results suggest that the polymorphism associated with
      atherosclerosis in type1 DM is Apo E4/E4.

PMID- 22394701
TI  - Neurocognitive functions in children and adolescents with subclinical
      hypothyroidism.
AB  - OBJECTIVE: Hypothyroidism is a metabolic condition that can lead to cognitive and
      behavioral deficits in children and adolescents. However, there is less evidence
      about subclinical hypothyroidism (SH) as a risk factor for neuropsychological
      disorders in childhood. The aim of this study was to evaluate cognitive functions
      like active/passive attention, maintaining attention, and response inhibition in
      pediatric patients with SH. METHODS: Seventeen patients (between 7-17 years old)
      with SH were tested with the Stroop test, Verbal Fluency test and the sub-tests
      of the Wechsler intelligence scale for children-Revised (WISC-R). SH diagnosis
      was based on the mild increase of serum thyrotropin (TSH) level together with a
      normal serum free thyroxine level and an exaggerated TSH response to thyrotropin
      releasing hormone. RESULTS: Out of seventeen cases, 10 (59%) were girls and 7
      (41%) were boys. Six cases were obese and 5 were overweight. The children in the
      SH group, as compared to the control group, obtained significantly lower scores
      on both the Digit Span subtest of the WISC-R and the Stroop subtests, which are
      sensitive to attention. No significant differences were found between the SH
      group and the healthy controls in verbal fluency and encoding tests. CONCLUSION:
      In this study, pediatric patients with SH showed poor performance in tests
      measuring attention. Therefore, we want to stress the importance of close
      collaboration between pediatric endocrinology and child and adolescent psychiatry
      departments.

PMID- 22394702
TI  - Synchronous occurrence of papillary carcinoma in the thyroid gland and
      thyroglossal duct in an adolescent with congenital hypothyroidism.
AB  - Thyroid carcinoma (TC) combined with congenital hypothyroidism is rare. The
      synchronous occurrence of these two conditions is even rarer. We describe a
      patient with congenital hypothyroidism in whom hyperthyroglobulinemia and nodules
      developed despite adequate replacement therapy. Papillary TC was detected at age
      19 years. Postoperative diagnostic scintigraphy showed increased uptake in the
      thyroglossal duct region. Repetitive imaging of the thyroid gland can be useful
      in the early detection of TC in patients with congenital hypothyroidism.
      Moreover, this rare situation can be complicated by a synchronous thyroglossal
      duct carcinoma. Thyroglossal duct carcinoma can be detected if diagnostic
      scintigraphy is performed after total thyroidectomy.

PMID- 22394704
TI  - Delirium in diabetic ketoacidosis: a case report.
AB  - A 15-year-old female patient with known type 1 diabetes mellitus was referred
      because of abdominal pain. On admission, she was alert but dehydrated with marked
      Kussmaul breathing. Blood glucose was 414 mg/dL (23 mmol/L). Blood gas analysis
      revealed severe metabolic acidosis (pH: 6.99) with an elevated anion gap (29.8
      mmol/L) and an increased base excess (-25.2 mmol/L). At the sixth hour of
      treatment with intravenous fluids and insulin, the patient became delirious. The
      delirium persisted despite the normalization of the acidosis and became difficult
      to manage. Brain imaging studies revealed neither brain edema nor other
      intracranial pathology. No evidence of intoxication could be found. The patient
      gradually regained consciousness and was diagnosed as a case of severe diabetic
      ketoacidosis (DKA) associated with infection. We were unable to find a similar
      case in the pediatric literature and thought that reporting this unusual case
      would be a contribution to the literature on DKA in children.

PMID- 22394703
TI  - Hypophosphatasia presenting with pyridoxine-responsive seizures, hypercalcemia,
      and pseudotumor cerebri: case report.
AB  - Hypophosphatasia (HPP) is an inborn error of metabolism characterized by
      defective bone mineralization caused by a deficiency in alkaline phosphatase
      (ALP) activity due to mutations in the tissue-nonspecific ALP (TNALP) gene. The
      clinical expression of the disease is variable. Six forms of HPP are identified
      according to age at presentation and clinical features. Patients with the
      infantile form are normal at birth. First symptoms appear within the first 6
      months of life. Along with skeletal findings, HPP patients may present with
      hypercalcemia, seizures, pseudotumor cerebri, and pulmonary insufficiency.
      Seizures in HPP are refractory to conventional antiepileptic drugs, but are
      responsive to pyridoxine. Herein, we report a case of HPP who presented with
      pyridoxine-responsive seizures in the early neonatal period and was found to have
      hypercalcemia, skeletal demineralization and increased intracranial pressure.

PMID- 22394705
TI  - Pseudohypoparathyroidism presenting with ventricular arrhythmia: a case report.
AB  - Pseudohypoparathyroidism (PHP) is a rare disorder characterized by varying
      degrees of unresponsiveness to parathyroid hormone. Patients usually present with
      hypocalcemia-induced seizures or tetany, whereas no case of hypocalcemia-induced
      cardiac arrhythmia in PHP has been described to date. In this paper, we report
      the case of a male adolescent with PHP type 1a who presented with hypocalcemia
      induced ventricular extrasystoles (bigeminy, trigeminy) and mild corrected QT
      interval prolongation. The patient had brachydactyly and his second fingers and
      toes were longer than the others, a finding consistent with PHP. Laboratory tests
      detected hypomagnesemia, as well as elevated levels of creatine kinase and
      lactate dehydrogenase. Ventricular arrhythmia and abnormal laboratory tests
      improved with calcium supplementation and vitamin D treatment. The findings in
      this patient suggest that hypomagnesemia may make patients with PHP more
      susceptible to hypocalcemia and may thus prompt a state of hypocalcemia-induced
      arrhythmia or other cardiac complications.

PMID- 22394706
TI  - Anogenital distance in Turkish newborns.

PMID- 22394708
TI  - The pediatric endocrinology forum: summer camps for diabetic children in the
      southeastern regions of Turkey.

PMID- 22394709
TI  - Vitamin D deficiency in children and adolescents.
AB  - OBJECTIVE: Vitamin D deficiency is an important health problem in both developed
      and developing countries. Recent reports on the extraskeletal effects of vitamin
      D have led to increased interest in prevalence studies on states of
      deficiency/insufficiency of vitamin D. The aim of this study was to determine the
      frequency of vitamin D deficiency and insufficiency in children and adolescents
      residing in Ankara, Turkey and to investigate the factors associated with low
      vitamin D status. METHODS: A total of 440 children and adolescents aged between 0
      and 16 years were enrolled in this study. The subjects were divided into three
      groups according to their vitamin D status (deficiency <=15 ng/mL; insufficiency:
      15-20 ng/mL; sufficiency >=20 ng/mL) and also according to their age (preschool<5
      years; middle childhood: 5-10 years; adolescence: 11-16 years). RESULTS: Overall,
      40% of the subjects were found to have 25 hydroxy vitamin D [25(OH)D] levels of
      less than 20 ng/mL. The levels indicated a deficiency state in 110 subjects (25%)
      and insufficiency - in 66 (15%). The rate of vitamin D deficiency was higher in
      girls, regardless of age. 25(OH)D levels correlated negatively with age (r=-0.48,
      p<0.001), body mass index (BMI) (r=-0.20, p=0.001) and intact parathyroid hormone
      (iPTH) level (r=-0.31, p=0.001). A positive correlation was observed between
      25(OH)D and serum ferritin levels (r=0.15, p=0.004). CONCLUSIONS: The high
      frequency of vitamin D deficiency in childhood (especially among adolescent
      girls) indicates a need for supplementation and nutritional support.

PMID- 22394711
TI  - A new perspective on severe nuclear accidents.
AB  - The reactions of the public in Korea to the nuclear accident at the Fukushima
      Daiichi plants in Japan, particularly over-reactions, are reviewed, with the
      conclusion that significant radioactive contamination of a small country could
      lead to a severe national crisis. The most important factor is the socio-economic
      damage caused by stigma, which in turn is caused by a misunderstanding of the
      radiation risk. Given that nuclear power is an important choice in the face of
      the threat of climate change, the public's perceptions need to be changed at any
      cost, not only in those countries operating nuclear power plants but globally as
      well.

PMID- 22394710
TI  - DNA barcoding in native plants of the Labiatae (Lamiaceae) family from Chios
      Island (Greece) and the adjacent Cesme-Karaburun Peninsula (Turkey).
AB  - The plant family Labiatae (Lamiaceae) is known for its fine medicinal and
      aromatic herbs like lavender, mint, oregano, sage and thyme and is a rich source
      of essential oils for the food, pharmaceutical and cosmetic industry. Besides its
      great economic importance, the Labiatae family contributes significantly to the
      endemic flora of Greece and Turkey. Owing to its economic and biological
      significance and to the difficult identification based on morphological
      characters of several of its taxa, the Labiatae family is an ideal case for
      developing DNA barcodes. The purpose of this study is to evaluate the utility of
      DNA barcoding on a local scale in discriminating Labiatae species in Chios Island
      (Greece) and the adjacent Cesme-Karaburun Peninsula (Turkey). We chose three
      cpDNA regions (matK, rbcL, trnH-psbA) that were proposed by previous studies and
      tested them either as single region or as multiregion barcodes based on the
      criteria determined by Consortium for the Barcode of Life (CBOL). Our results
      show that matK and trnH-psbA taken as useful in discriminating species of the
      Labiatae, for the species we examined, as any multiregion combination. matK and
      trnH-psbA could serve as single-region barcodes for Labiatae species contributing
      to the conservation and the trade control of valuable plant resources.

PMID- 22394712
TI  - Intrafollicular conditions as a major link between maternal metabolism and oocyte
      quality: a focus on dairy cow fertility.
AB  - Reduced oocyte and embryo quality are recognised as major factors in the problem
      of disappointing fertility in high producing dairy cows. This review aims to shed
      more light on the importance of the intrafollicular environment in the
      subfertility problem in dairy cows. Metabolic disturbances associated with
      negative energy balance (NEB) early postpartum are associated with ovarian
      dysfunction. Changes in the growth pattern of the ovarian follicle during a
      period of NEB can indirectly affect oocyte quality. Furthermore, a maternal
      metabolic disorder (linked with NEB or nutritionally induced) may alter the
      endocrine and biochemical composition of the follicular fluid, the micro
      environment of the growing and maturing female gamete. The maturing oocyte is
      very sensitive to any perturbation in its direct environment and in vitro
      maturation models revealed that some of these metabolic changes reduce the
      oocyte's developmental competence. Also, embryo quality is significantly reduced
      due to maturation in adverse conditions. Well balanced and timed oocyte
      metabolism and gene expression are crucial to safeguard an optimal oocyte
      development. In that perspective, metabolome and transcriptome parameters of the
      oocyte may serve to predict reproductive success rates. Finally, there is growing
      evidence that adverse conditions for oocyte growth and maturation may also
      jeopardise the health and performance of the offspring.

PMID- 22394713
TI  - Modification of spermatozoa quality in mature small ruminants.
AB  - This review is based largely, but not entirely, on the assumption that gamete
      quality is directly linked to sperm output and thus testicular mass, an approach
      made necessary by the absence of a large body of data on factors that affect
      gamete quality in ruminants. On the other hand, there is a change in the
      efficiency of sperm production per gram of testicular tissue when the testis is
      growing or shrinking, a clear indicator of changes in the rates of cell loss
      during the process of spermatogenesis, probably through apoptosis. We therefore
      postulate that the spermatozoa that do survive when the testis is shrinking are
      of a lower quality than those that are produced when the testis is growing and
      the rate of sperm survival is increasing. In adult small ruminants in particular,
      testicular mass and sperm production are highly labile and can be manipulated by
      management of photoperiod (melatonin), nutrition, genetics and behaviour ('mating
      pressure'). Importantly, these factors do not act independently of each other -
      rather, the outcomes in terms of sperm production are dictated by interactions.
      It therefore seems likely that spermatozoa quality will be affected by these same
      factors, but definitive answers await detailed studies.

PMID- 22394714
TI  - Growth hormone regulation of follicular growth.
AB  - The somatotropic axis-consisting of growth hormone (GH), the insulin-like growth
      factors 1 and 2 (IGF1 and IGF2), GH binding protein (GHBP), IGF binding proteins
      (IGFBPs) 1 to 6, and the cell-surface receptors for GH and the IGFs-has major
      effects on growth, lactation and reproduction. The primary target tissues for GH
      are involved in growth and metabolism. The functionality of the somatotropic axis
      depends in part on the expression of liver GH receptor (GHR), which determines
      the amount of IGF1 released from the liver in response to GH. The IGF1 acts as a
      pleiotropic growth factor and also serves as the endocrine negative feedback
      signal controlling pituitary GH secretion. Growth hormone and IGF1 undergo
      dynamic changes throughout the life cycle, particularly when animals are either
      growing, early post partum or lactating. Cells within the reproductive tract can
      respond directly to GH but to a lesser degree than the primary target tissues.
      The major impact that GH has on reproduction, therefore, may be secondary to its
      systemic effects on metabolism (including insulin sensitivity) or secondary to
      the capacity for GH to control IGF1 secretion. Insulin-like growth factor 1 and
      IGFBP are also synthesised within the ovary and this local synthesis is a
      component of the collective IGF1 action on the follicle. Future studies of GH
      should focus on its direct effects on the follicle as well as its indirect
      effects mediated by shifts in nutrient metabolism, insulin sensitivity, IGF1 and
      IGFBP.

PMID- 22394715
TI  - The impact of obesity on oocytes: evidence for lipotoxicity mechanisms.
AB  - Obesity can have detrimental effects on pregnancy rates in natural conceptions
      and also in women undergoing IVF or intracytoplasmic sperm injection (ICSI). This
      review summarises the most recent clinical literature investigating whether
      obesity impacts oocyte quality and early embryo growth. In other tissues, obesity
      leads to lipotoxicity responses including endoplasmic reticulum stress,
      mitochondrial dysfunction and apoptosis. Recent reports indicate that
      lipotoxicity is a mechanism by which obesity may impact oocyte quality.

PMID- 22394716
TI  - Adaptive responses of the embryo to maternal diet and consequences for post
      implantation development.
AB  - Maternal periconceptional (PC) nutrition, coupled with maternal physiological
      condition, can impact on reproductive performance and potential across mammalian
      species. Oocyte quality and embryo development are affected adversely by either
      nutrient restriction or excess. Moreover, the quality of maternal PC nutrition
      can have lasting effects through fetal development and postnatally into
      adulthood. Chronic disease, notably cardiovascular and metabolic disease, and
      abnormal behaviour have been identified in adult offspring in small and large
      animal models of PC nutrient restriction. These long-term effects associate with
      compensatory responses that begin from the time of early embryo development. This
      review assesses the field of PC nutrition in vivo on short- and long-term
      developmental consequences in rodent and ruminant models and considers the
      implications for human health.

PMID- 22394717
TI  - Periconceptional influences on offspring sex ratio and placental responses.
AB  - Maternal diet and secondary factors can strikingly influence fetal outcomes,
      including biasing offspring sex ratio and altering the molecular biological
      responses of the conceptus, namely within the placenta. Alterations in the in
      utero environment might also lead to profound developmental origin of health and
      disease (DOHaD) outcomes into adulthood, including increased risk for
      cardiovascular disease, obesity and cancer, with males in general being at
      greater risk for these diseases. Female mice maintained on a very high fat (VHF)
      diet birth more sons than those on a chow-based and low fat (LF), high
      carbohydrate diet, with the latter group producing more daughters. However,
      neither the underlying mechanisms that contribute to this shift in offspring sex
      ratio nor when they occur during pregnancy have been resolved. In this review, we
      consider the evidence that maternal diet and other factors influence secondary
      sex ratio in a variety of species, including humans, and discuss when this
      skewing might occur. Additionally, we examine how fetal sex and maternal diet
      influences gene expression patterns in the mouse placenta, which serves as the
      primary nutrient acquisition and communication organ between the mother and her
      developing pups. These adaptations to diet observed as changes in gene expression
      are likely to provide insight into how the placenta buffers the fetus proper from
      environmental shifts in nutrient availability during pregnancy and whether male
      and female conceptuses respond differently to such challenges.

PMID- 22394718
TI  - The role of fatty acids in oocyte and early embryo development.
AB  - Growing evidence suggests that endogenous and exogenous fatty acids play diverse
      roles in developing mammalian oocytes and early embryos. In this review, we
      describe some of the regulatory roles of fatty acids in early development, in
      addition to their metabolic functions. We focus initially on the provision of
      individual fatty acids, and then discuss how these might affect metabolism,
      oxidative stress, membrane composition, cell signalling events and gene
      expression. We propose that ongoing research should focus on physiologically
      relevant ratios and combinations of fatty acids, rather than isolated individual
      fatty acids, as their combined roles are both subtle and complex. Changing the
      ratio of specific fatty acids in the diet of animal models, and in vitro culture
      medium can cause significant dysregulation of cellular processes and development,
      an issue that extends to human fertility.

PMID- 22394719
TI  - Novel aspects of endometrial function: a biological sensor of embryo quality and
      driver of pregnancy success.
AB  - Successful pregnancy depends on complex biological processes that are regulated
      temporally and spatially throughout gestation. The molecular basis of these
      processes have been examined in relation to gamete quality, early blastocyst
      development and placental function, and data have been generated showing
      perturbations of these developmental stages by environmental insults or embryo
      biotechnologies. The developmental period falling between the entry of the
      blastocyst into the uterine cavity to implantation has also been examined in
      terms of the biological function of the endometrium. Indeed several mechanisms
      underlying uterine receptivity, controlled by maternal factors, and the maternal
      recognition of pregnancy, requiring conceptus-produced signals, have been
      clarified. Nevertheless, recent data based on experimental perturbations have
      unveiled unexpected biological properties of the endometrium (sensor/driver) that
      make this tissue a dynamic and reactive entity. Persistent or transient
      modifications in organisation and functionality of the endometrium can
      dramatically affect pre-implantation embryo trajectory through epigenetic
      alterations with lasting consequences on later stages of pregnancy, including
      placentation, fetal development, pregnancy outcome and post-natal health.
      Developing diagnostic and prognostic tools based on endometrial factors may
      enable the assessment of maternal reproductive capacity and/or the developmental
      potential of the embryo, particularly when assisted reproductive technologies are
      applied.

PMID- 22394720
TI  - Environmental regulation of placental phenotype: implications for fetal growth.
AB  - Environmental conditions during pregnancy determine birthweight, neonatal
      viability and adult phenotype in human and other animals. In part, these effects
      may be mediated by the placenta, the principal source of nutrients for fetal
      development. However, little is known about the environmental regulation of
      placental phenotype. Generally, placental weight is reduced during suboptimal
      conditions like maternal malnutrition or hypoxaemia but compensatory adaptations
      can occur in placental nutrient transport capacity to help maintain fetal growth.
      In vivo studies show that transplacental glucose and amino acid transfer adapt to
      the prevailing conditions induced by manipulating maternal calorie intake,
      dietary composition and hormone exposure. These adaptations are due to changes in
      placental morphology, metabolism and/or abundance of specific nutrient
      transporters. This review examines environmental programming of placental
      phenotype with particular emphasis on placental nutrient transport capacity and
      its implications for fetal growth, mainly in rodents. It also considers the
      systemic, cellular and molecular mechanisms involved in signalling environmental
      cues to the placenta. Ultimately, the ability of the placenta to balance the
      competing interests of mother and fetus in resource allocation may determine not
      only the success of pregnancy in producing viable neonates but also the long-term
      health of the offspring.

PMID- 22394721
TI  - Programming the offspring through altered uteroplacental hemodynamics: how
      maternal environment impacts uterine and umbilical blood flow in cattle, sheep
      and pigs.
AB  - As placental growth and vascularity precedes exponential fetal growth, not only
      is proper establishment of the placenta important, but also a continual
      plasticity of placental function throughout gestation. Inadequate maternal
      environment, such as nutritional plane, has been documented to alter fetal
      organogenesis and growth, thus leading to improper postnatal growth and
      performance in many livestock species. The timing and duration of maternal
      nutritional restriction appears to influence the capillary vascularity,
      angiogenic profile and vascular function of the placenta in cattle and sheep. In
      environments where fetal growth and/or fetal organogenesis are compromised,
      potential therapeutics may augment placental nutrient transport capacity and
      improve offspring performance. Supplementation of specific nutrients, including
      protein, as well as hormone supplements, such as indolamines, during times of
      nutrient restriction may assist placental function. Current use of Doppler
      ultrasonography has allowed for repeated measurements of uterine and umbilical
      blood flow including assessment of uteroplacental hemodynamics in cattle, sheep
      and swine. Moreover, these variables can be monitored in conjugation with
      placental capacity and fetal growth at specific time points of gestation.
      Elucidating the consequences of inadequate maternal intake on the continual
      plasticity of placental function will allow us to determine the proper timing and
      duration for intervention.

PMID- 22394722
TI  - Evidence for similar changes in offspring phenotype following either maternal
      undernutrition or overnutrition: potential impact on fetal epigenetic mechanisms.
AB  - The goal of this review is to shed light on the role of maternal malnutrition in
      inducing epigenetic changes in gene expression, leading to alterations in fetal
      growth and development, and to altered postnatal phenotype and the development of
      metabolic disease. We present evidence supporting the concept that both maternal
      undernutrition and overnutrition can induce the same cadre of fetal organ and
      tissue abnormalities and lead to the same postnatal metabolic changes in the
      resulting offspring. Furthermore, we present evidence that in both overnourished
      and undernourished ovine pregnancies, fetuses experience a period of nutrient
      restriction as a result of alterations in placental delivery of maternal
      nutrients into the fetal compartment. We argue that this bout of reduced fetal
      nutrition in undernourished and overnourished pregnancies leads to the
      development of a thrifty phenotype in which the fetus attempts to alter the
      function of its tissues and organs to maximise its chances of survival in a
      postnatal environment that is deficient in nutrients. Importantly, we present
      evidence to support the concept that these phenotypic changes in offspring
      quality resulting from maternal malnutrition are transmitted to subsequent
      generations, independent of their maternal nutritional inputs.

PMID- 22394963
TI  - The physiology of multifactorial problems limiting the establishment of pregnancy
      in dairy cattle.
AB  - The failure of cows to successfully establish pregnancy after insemination is an
      important limiting factor for the efficiency of dairy production systems. The
      physiological reasons for this are many and pertain to the post partum and early
      pregnancy periods. Cows that suffer severe negative energy balance after
      parturition are prone to diseases (including uterine infection) that are, in
      part, explained by reduced function of the immune system, having negative
      consequences for subsequent fertility. In high-producing dairy cows, the duration
      and intensity of oestrus is low as a consequence of low circulating oestradiol
      concentrations, and after insemination, high embryo mortality is the single
      biggest factor reducing calving rates. Embryo mortality occurs as consequences of
      poor oocyte quality (probably caused by the adverse metabolic environment) and by
      poor maternal uterine environment (probably caused by carry-over effects of
      uterine infection and low circulating progesterone concentrations). Immediate
      improvements in the fertility of lactating cows on many farms can be achieved by
      applying existing knowledge, but longer-term sustained improvement will require
      additional knowledge in many areas including the physiology of the tissues that
      contribute to reproduction.

PMID- 22394964
TI  - Improving fertility to timed artificial insemination by manipulation of
      circulating progesterone concentrations in lactating dairy cattle.
AB  - This manuscript reviews the effect of progesterone (P4) during timed AI protocols
      in lactating dairy cows. Circulating P4 is determined by a balance between P4
      production, primarily by the corpus luteum (CL), and P4 metabolism, primarily by
      the liver. In dairy cattle, the volume of luteal tissue is a primary determinant
      of P4 production; however, inadequate circulating P4 is generally due to high P4
      metabolism resulting from extremely elevated liver blood flow. Three sections in
      this manuscript summarise the role of P4 concentrations before breeding, near the
      time of breeding and after breeding. During timed AI protocols, elevations in P4
      are generally achieved by ovulation, resulting in an accessory CL, or by
      supplementation with exogenous P4. Elevating P4 before timed AI has been found to
      decrease double ovulation and increase fertility to the timed AI. Slight
      elevations in circulating P4 can dramatically reduce fertility, with inadequate
      luteolysis to the prostaglandin F2alpha treatment before timed AI being the
      underlying cause of this problem. After AI, circulating P4 is critical for embryo
      growth, and for establishment and maintenance of pregnancy. Many studies have
      attempted to improve fertility by elevating P4 after timed AI with marginal
      elevations in fertility. Thus, previous research has provided substantial
      insights into mechanisms regulating circulating P4 concentrations and actions.
      Understanding this prior research can focus future research on P4 manipulation to
      improve timed AI protocols.

PMID- 22394965
TI  - Embryo death in cattle: an update.
AB  - For heifers, beef and moderate-yielding dairy cows, fertilisation generally
      exceeds 90%. In high-producing dairy cows, it may be lower and possibly more
      variable. The major component of embryo loss occurs before Day 16 following
      breeding, with emerging evidence of greater losses before Day 8 in high-producing
      dairy cows. Late embryo loss causes serious economic losses because it is often
      recognised too late to rebreed females. Systemic concentrations of progesterone
      during the cycles both preceding and following insemination affect embryo
      survival; too-high or too-low a concentration has been shown to be negatively
      associated with survival rate. Energy balance and dry matter intake during the 4
      weeks after calving are critically important in determining conception rate when
      cows are inseminated 70 to 100 days after calving. More balanced breeding
      strategies with greater emphasis on fertility, feed intake and energy must be
      developed. Genetic variability for fertility traits can be exploited; genomic
      technology will not only provide scientists with an improved understanding of the
      underlying biological processes involved in fertilisation and the establishment
      of pregnancy, but could identify genes responsible for improved embryo survival.
      Their incorporation into breeding objectives would increase the rate of genetic
      progress for embryo survival. There is a range of easily adoptable management
      factors, under producer control, that can either directly increase embryo
      survival or ameliorate the consequences of low embryo survival rates. The
      correction of minor deficits in several areas can have a substantial overall
      effect on herd reproductive performance.

PMID- 22394966
TI  - The effects of endometritis on the establishment of pregnancy in cattle.
AB  - Endometritis is common in post partum dairy cows and is associated with impaired
      reproductive performance reflected in reduced first service conception, reduced
      hazard of pregnancy over the breeding period and increased risk of reproductive
      culling. The observed effects may be mediated directly by bacterial products,
      such as lipopolysaccharide (LPS, endotoxin), or indirectly by inflammatory
      mediators, such as cytokines, eicosanoids, nitric oxide and oxidative stress
      affecting sperm, ovarian, uterine and embryonic function. An inflammatory milieu
      in the uterus has been associated with changes in sperm motility and function as
      well as increased sperm phagocytosis. Zygotes resulting from fertilisation of
      oocytes with sperm subjected to oxidative stress are less likely to develop to
      the blastocyst stage. In addition, LPS and tumour necrosis factor-alpha
      (TNFalpha) impair follicular steroidogenesis, growth and ovulation. Oocytes
      exposed to LPS or prostaglandin (PG) F(2alpha) during maturation are less likely
      to develop to blastocyst stage after fertilisation. Embryos exposed to
      inflammatory mediators during development have fewer trophoectoderm cells. Nitric
      oxide impairs development of preimplantation embryos and TNFalpha increases
      blastomere apoptosis. Endometritis in women has been associated with higher rates
      of implantation failure. Extragenital inflammation (e.g. mastitis) is also
      associated with an increased rate of embryonic loss in cattle. These observations
      make it clear that direct and indirect effects of endometritis, and inflammation
      in general, can interrupt successful reproduction at several crucial stages.

PMID- 22394967
TI  - The use of endocrine treatments to improve pregnancy rates in cattle.
AB  - Reproduction is critical for the success of both dairy and beef cattle
      production. Inadequate reproduction impairs profitability by compromising
      production, delaying genetic progress and increasing expenses. A major impediment
      to the use of artificial insemination (AI) is the ability to detect oestrus for
      optimum timing of breeding. However, increased understanding of the bovine
      oestrous cycle has led to the development of reproductive programmes that allow
      precise synchrony of follicle development, luteal regression and ovulation. The
      advent of timed-AI protocols revolutionised reproductive management in dairy and
      beef herds. It allows for AI at a more desired time post partum despite oestrous
      cyclicity. It also allows for pre-determined re-insemination of cows diagnosed as
      not pregnant. In subfertile cows, such as the post partum, anoestrous beef cow
      and the high-producing dairy cow, strategic hormone supplementation has been used
      to overcome hormone deficiencies and improve pregnancy rates. Several
      physiological windows have been identified to optimise fertility in
      synchronisation programmes and they include, but are not limited to, follicle
      turnover, synchrony of follicular development, length of dominance, progesterone
      concentrations during development of the ovulatory follicle, luteal regression,
      peri-ovulatory steroid concentrations, length of pro-oestrus, synchrony of
      ovulation and AI, and progesterone rise after ovulation.

PMID- 22394968
TI  - Impact of circulating concentrations of progesterone and antral age of the
      ovulatory follicle on fertility of high-producing lactating dairy cows.
AB  - Dairy cow infertility negatively affects profit of dairy production enterprises
      around the world, and enhancing conception rates of dairy cows is a critical
      management issue to resolve. It appears that conception rates of dairy cows are
      attenuated due to reduced progesterone concentrations in circulation during
      growth of the ovulatory follicle. It is not clear how reduced progesterone
      influences fertility, but data presented in this brief review suggest that it can
      be somewhat reversed through increasing concentrations of progesterone during the
      growth of the ovulatory follicle before luteolysis. Ovsynch protocols may be
      utilised to enhance progesterone concentrations through the induction of an
      accessory corpus luteum (CL) following the initial gonadotropin-releasing hormone
      (GnRH) treatment. Cows at Day 13 of the oestrous cycle with a 7-day-old accessory
      CL had ~50% more progesterone at the time of prostaglandin injection of Ovsynch
      compared with cows with only a Day 13 CL. Ovsynch can consistently induce an
      accessory CL following the initial GnRH treatment if cows are on Days 6 or 7 of
      the oestrous cycle at the time of treatment. Pre-synchrony strategies are
      critical to enhance the probability that cows will be on Days 6 or 7 at first
      GnRH treatement of Ovsynch.

PMID- 22394969
TI  - Treatments for the synchronisation of bovine recipients for fixed-time embryo
      transfer and improvement of pregnancy rates.
AB  - Although embryo transfer technology has been used commercially in cattle for many
      years, the inefficiency of oestrus detection, especially in recipients, has
      limited the widespread application of this technology. The most useful
      alternative to increase the number of recipients utilised in an embryo transfer
      program is the use of protocols that allow for embryo transfer without the need
      for oestrus detection, usually called fixed-time embryo transfer (FTET). Most
      current FTET protocols are based on progestin-releasing devices combined with
      oestradiol or GnRH, which control and synchronise follicular wave dynamics and
      ovulation. Conception rates to a single FTET have been reported to be similar to
      those after detection of oestrus, but pregnancy rates are higher because these
      treatments have increased the proportion of recipients that receive an embryo.
      Recent changes to treatments for FTET, such as the administration of eCG, have
      resulted in increased pregnancy rates and provide opportunities to make these
      treatments easier to perform on farm.

PMID- 22394970
TI  - The evolution of improved and simplified superovulation protocols in cattle.
AB  - Superovulation protocols have improved greatly since the early days of bovine
      embryo transfer when purified gonadotrophins were not available, follicular wave
      dynamics were unknown physiological phenomena and prostaglandins were not
      available. Although superstimulatory protocols in cattle are normally initiated
      mid-cycle, elective control of follicular wave emergence and ovulation have had a
      great impact on the application of on-farm embryo transfer. However, the most
      common treatment for the synchronisation of follicular wave emergence involves
      the use of oestradiol, which cannot be used in many parts of the world.
      Therefore, the need for alternative treatments has driven recent research. An
      approach that has shown promise is to initiate follicle-stimulating hormone (FSH)
      treatments at the time of the emergence of the new follicular wave following
      ovulation induced by gonadotrophin-releasing hormone. Alternatively, it has been
      shown that it may be possible to ignore follicular wave status and, by extending
      the treatment protocol, induce subordinate follicles to superovulate. Finally,
      the short half-life of pituitary FSH necessitates twice-daily treatments, which
      are time-consuming, stressful and subject to error. Recent treatment protocols
      have permitted superstimulation with a single FSH treatment or two treatments 48h
      apart, reducing the need for animal handling during gonadotrophin treatments.

PMID- 22394983
TI  - Denosumab dose selection for patients with bone metastases from solid tumors.
AB  - PURPOSE: To quantitatively characterize the longitudinal dose exposure-response
      [urinary N-telopeptide normalized to urinary creatinine (uNTx/Cr) suppression]
      relationship for denosumab in patients with bone metastases from solid tumors.
      EXPERIMENTAL DESIGN: Data from 373 patients who received denosumab as single or
      multiple subcutaneous doses ranging from 30 to 180 mg (or 0.01 to 3 mg/kg)
      administered every 4 or 12 weeks for up to 3 years were used in this analysis. An
      inhibitory sigmoid I(Max) model was used to characterize the time course of
      uNTx/Cr as a function of serum denosumab concentrations and the M3 method was
      used to analyze the 52% of uNTx/Cr values below the limit of quantification in
      the context of a mixed-effects model. Age, weight, sex, race, and cancer type
      were evaluated as potential covariates for model parameters. Model-based
      simulations were undertaken to explore and predict the role of denosumab dose and
      dosing intervals on uNTx/Cr suppression. RESULTS: The typical value (between
      subject variability; %) for uNTx/Cr at baseline was 49.2 nmol/L/mmol/L (76.8%),
      denosumab maximal uNTx/Cr suppression (efficacy) was 93.7% (127%), and the
      denosumab concentration providing half-maximal uNTx/Cr suppression (potency) was
      31.8 ng/mL (287%). No effect of covariates on denosumab efficacy and potency was
      identified. Simulations indicated that a s.c. denosumab dose of 120 mg
      administered every 4 weeks provides more than 90% suppression of uNTx/Cr in the
      maximum proportion of patients relative to other every 4- and 12-week doses
      evaluated. CONCLUSIONS: Over the wide range of dosing regimens examined, a s.c.
      denosumab dose of 120 mg administered every 4 weeks is the optimal dosing regimen
      to suppress uNTx/Cr in patients with bone metastases from solid tumors. Clin
      Cancer Res; 18(9); 2648-57. (c)2012 AACR.

PMID- 22394984
TI  - Pharmacokinetics and safety of bortezomib in patients with advanced malignancies
      and varying degrees of liver dysfunction: phase I NCI Organ Dysfunction Working
      Group Study NCI-6432.
AB  - PURPOSE: The proteasome inhibitor bortezomib undergoes oxidative hepatic
      metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate
      bortezomib pharmacokinetics and safety in patients with varying degrees of
      hepatic impairment, to inform dosing recommendations in these special
      populations. EXPERIMENTAL DESIGN: Patients received bortezomib on days 1, 4, 8,
      and 11 of 21-day cycles. Patients were assigned to four hepatic function groups
      based on the National Cancer Institute Organ Dysfunction Working Group
      classification. Those with normal function received bortezomib at the 1.3 mg/m(2)
      standard dose. Patients with severe, moderate, and mild impairment received
      escalating doses from 0.5, 0.7, and 1.0 mg/m(2), respectively, up to a 1.3
      mg/m(2) maximum. Serial blood samples were collected for 24 hours postdose on
      days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. RESULTS:
      Sixty-one patients were treated, including 14 with normal hepatic function and
      17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild
      hepatic impairment did not alter dose-normalized bortezomib exposure (AUC(0
      tlast)) or C(max) compared with patients with normal function. Mean dose
      normalized AUC(0-tlast) was increased by approximately 60% on day 8 in patients
      with moderate or severe impairment. CONCLUSIONS: Patients with mild hepatic
      impairment do not require a starting dose adjustment of bortezomib. Patients with
      moderate or severe hepatic impairment should be started at a reduced dose of 0.7
      mg/m(2).

PMID- 22394986
TI  - H2O on Pt(111): structure and stability of the first wetting layer.
AB  - We study the structure and stability of the first water layer on Pt(111) by
      variable-temperature scanning tunneling microscopy. We find that a high Pt step
      edge density considerably increases the long-range order of the equilibrium ?37 *
      ?37R25.3 degrees - and ?39 * ?39R16.1 degrees -superstructures, presumably due to
      the capability of step edges to trap residual adsorbates from the surface.
      Passivating the step edges with CO or preparing a flat metal surface leads to the
      formation of disordered structures, which still show the same structural elements
      as the ordered ones. Coadsorption of Xe and CO proves that the water layer covers
      the metal surface completely. Moreover, we determine the two-dimensional crystal
      structure of Xe on top of the chemisorbed water layer which exhibits an Xe-Xe
      distance close to the one in bulk Xe and a rotation angle of 90 degrees  between
      the close-packed directions of Xe and the close-packed directions of the
      underlying water layer. CO is shown to replace H(2)O on the Pt(111) surface as
      has been deduced previously. In addition, we demonstrate that tunneling of
      electrons into the antibonding state or from the bonding state of H(2)O leads to
      dissociation of the molecules and a corresponding reordering of the adlayer into
      a ?3 * ?3R30 degrees -structure. Finally, a so far not understood restructuring
      of the adlayer by an increased tunneling current has been observed.

PMID- 22394985
TI  - Acute liver failure, multiorgan failure, cerebral oedema, and activation of
      proangiogenic and antiangiogenic factors in a case of Marburg haemorrhagic fever.
AB  - A woman developed Marburg haemorrhagic fever in the Netherlands, most likely as a
      consequence of being exposed to virus-infected bats in the python cave in
      Maramagambo Forest during a visit to Uganda. The clinical syndrome was dominated
      by acute liver failure with secondary coagulopathy, followed by a severe systemic
      inflammatory response, multiorgan failure, and fatal cerebral oedema. A high
      blood viral load persisted during the course of the disease. The initial systemic
      inflammatory response coincided with peaks in interferon-gamma and tumour
      necrosis factor-alpha concentrations in the blood. A terminal rise in interleukin
      6, placental growth factor (PlGF), and soluble vascular endothelial growth factor
      receptor-1 (sVEGF-R1) seemed to suggest an advanced pathophysiological stage of
      Marburg haemorrhagic fever associated with vascular endothelial dysfunction and
      fatal cerebral oedema. The excess of circulating sVEGF-R1 and the high sVEGF
      R1:PlGF ratio shortly before death resemble pathophysiological changes thought to
      play a causative part in pre-eclampsia. Aggressive critical-care treatment with
      renal replacement therapy and use of the molecular absorbent recirculation system
      appeared able to stabilise--at least temporarily--the patient's condition.

PMID- 22394987
TI  - Taking alcohol by deception: an analysis of ethanol concentration of "paraga" an
      alcoholic herbal mixture in Nigeria.
AB  - BACKGROUND: Alcohol related road traffic injuries are on the rise in Nigeria. A
      sizable proportion of the alcohol intake is disguised as herbal medicines which
      are commonly available at motor parks in most urban centres. This study aims to
      determine the ethanol concentration of the herbal preparations and the vendors'
      knowledge about their preparation and use. Twenty-eight samples of the paraga
      mixtures were obtained for analysis from 22 paraga vendors. The vendors were
      interviewed in the motor parks using a semi-structured questionnaire. RESULTS:
      All the paraga outlets were located in or near motor parks. Commercial motor
      drivers and motorcyclists accounted for most customers. There were no formal
      recipes, production involved no calibrations or weighing and thus the components
      and concentration of different batches varied. The alcohol by volume (ABV) of the
      samples ranged between 1.20% and 20.84%. Nine samples were weaker than beers
      (Alcohol By Volume (ABV) of 1-3.1%). Ten were equivalent to beer (ABV:3-8%) and
      the rest were equivalent to wine (ABV:8-12%) or stronger (ABV: 18-20%).
      CONCLUSIONS: Paraga should be classified as alcoholic beverages, and its sale
      restricted as such. The production should come under scrutiny, because the
      haphazard ways they are prepared may pose other health risks apart from those due
      to their alcoholic contents.

PMID- 22394988
TI  - The surgical management and outcome of congenital mediastinal malformations.
AB  - We reviewed our institutional experience with congenital mediastinal masses and
      compared the postnatal management and outcome of patients with or without
      prenatal diagnosis. Between January 1997 and August 2011, 24 patients underwent
      surgical procedures for congenital mediastinal mass. For eight patients, the mass
      was detected by prenatal ultrasonography at 27 weeks of gestation (range 22-35).
      Postnatal management consisted in open surgery for seven patients at a mean age
      of 9 months (range 1 day-20 months) and sclerotherapy for one lymphangioma at 5
      months of life. Sixteen patients had postnatal diagnosis at 137 months (+/-194)
      of median age. Eight bronchogenic cysts, seven bronchopulmonary foregut
      malformations, five teratomas, three lymphangiomas and one haemangioma were
      operated on. The median age at resection was 28 months (1 day-15 years). There
      were four emergency procedures and no surgical mortality. The median follow-up
      was 45 months (3-144). The duration of mechanical ventilation and hospital stay
      was, respectively, 4.6 h and 7.5 days for antenatal patients and 24.3 h and 14.3
      days for postnatal diagnosed patients. Prenatal diagnosis allows early management
      of congenital mediastinal malformations. Early resection can be performed prior
      to the occurrence of symptoms ~1 year of life and is associated with an excellent
      outcome and less morbidity.

PMID- 22394990
TI  - Community health workers improve contact tracing among immigrants with
      tuberculosis in Barcelona.
AB  - BACKGROUND: The important increase in immigration during recent years has changed
      the epidemiology and control strategies for tuberculosis (TB) in many places.
      This study evaluates the effectiveness of intervention with community health
      workers (CHW) to improve contact tracing among immigrants. METHODS: The study
      included all TB cases detected by the Barcelona TB Program from 2000 to 2005 and
      compared a period without CHW intervention (2000-2002) to a period with CHW
      intervention (2003-2005). The influence on contact tracing of sex, age, hospital
      of diagnosis, district of residence, birthplace, HIV, homeless and CHW
      intervention was analysed by logistic regression. Odds ratio (OR) and 95%
      confidence intervals (CI) were calculated. RESULTS: 960 foreign born TB cases
      were detected, 388 in the intervention period. Contact tracing was performed on
      65,7% of 201 smear-positive cases during the pre-intervention period compared to
      81.6% of 152 smear-positive TB cases during the intervention period (p < 0.001).
      Risk factors associated with incomplete contact tracing of smear-positive index
      cases included being diagnosed in two hospitals without contact tracing TB unit
      (OR = 3.5; CI:1.4-8.9) and (OR = 4.6; CI:1.6-13.5) respectively, birth place in
      India-Pakistan (OR = 4.4; CI:1.9-10.3) or North Africa (OR = 4.3; CI:1.8-10.5),
      having an unknown residence (OR = 5.4; CI:1.6-18.0), being HIV-infected (OR =
      6.1; CI:2.5-14.8) or homeless (OR = 3.3; CI:1.3-8.2), and the absence of CHW
      intervention (OR = 2.4; CI:1.3-4.3). CONCLUSIONS: The effectiveness of contact
      tracing for TB control in areas with high immigration can be improved by
      incorporating CHWs who act as translators, cultural mediators and facilitators
      who accompany cases and contacts through treatment and follow-up.

PMID- 22394989
TI  - Pectus excavatum: history, hypotheses and treatment options.
AB  - Pectus excavatum and pectus carinatum represent the most frequent chest wall
      deformations. However, the pathogenesis is still poorly understood and research
      results remain inconsistent. To focus on the recent state of knowledge, we
      summarize and critically discuss the pathological concepts based on the history
      of these entities, beginning with the first description in the sixteenth century.
      Based on the early clinical descriptions, we review and discuss the different
      pathogenetic hypotheses. To open new perspectives for the potential
      pathomechanisms, the embryonic and foetal development of the ribs and the sternum
      is highlighted following the understanding that the origin of these deformities
      is given by the disruption in the maturation of the parasternal region. In the
      second, different therapeutical techniques are highlighted and based on the
      pathogenetic hypotheses and the embryological knowledge potential new biomaterial
      based perspectives with interesting insights for tissue engineering-based
      treatment options are presented.

PMID- 22394991
TI  - Ultra-low reflectance, high absorption microcrystalline silicon nanostalagmite.
AB  - In this work, microcrystalline silicon nanostalagmite [MUc-SiNS] arrays have
      been successfully fabricated on glass by catalytic etching process through a
      template. The template, polystyrene [PS] nanospheres, with diameter and density
      of 30 to approximately 50 nm and 1010/cm2, respectively, was obtained by a
      modified nanophase separation of PS-containing block copolymer. The length of MUc
      SiNS could be controlled by the duration of etching time. The MUc-SiNS exhibits
      ultra-low reflection approximately 0.3% and absorption around 99% over 300 to 800
      nm in wavelength. Reflection is also suppressed for a wide range of angles of
      incidence in wide range of wavelength. This indicates the extensive light
      trapping effect by the MUc-SiNS and could possibly harvest a large amount of
      solar energy at infrared regime.

PMID- 22394992
TI  - Persistence of the immune response at 5 years of age following infant
      immunisation with investigational quadrivalent MenACWY conjugate vaccine
      formulations.
AB  - BACKGROUND AND AIMS: Serogroup A, C, W-135 and Y meningococcal (MenACWY)
      conjugate vaccines are recommended for routine adolescent immunisation in the
      United States and Canada. We evaluated the persistence of bactericidal antibodies
      through early childhood, following infant immunisation with varying schedules of
      MenACWY-CRM(197) vaccine. METHODS: UK and Canadian infants were immunised with 2
      3 doses of MenACWY-CRM(197) or 2 doses of serogroup C meningococcal (MenC)
      conjugate vaccine, and either MenACWY-CRM(197), 1/5 dose of MenACWY
      polysaccharide vaccine or no booster at 12 months. Control groups recruited at 60
      months had received country-specific infant doses of MenC conjugate vaccine. hSBA
      titres were measured in participants at 40 and 60 months of age. RESULTS: 382
      children were enrolled in 12 groups (22-40 per group). By age 60 months, 3-11% of
      children primed and boosted with MenACWY-CRM(197) had hSBA titres>=1:8 against
      serogroup A, 14-45% against serogroup C, 57-85% against serogroup W-135 and 42
      71% against serogroup Y. Children primed with MenC and boosted with MenACWY
      CRM(197) had similar results, except for serogroup C (59%). In age-matched
      controls administered MenC vaccine at 2, 3, and 4 months (UK), 2 and 12 months or
      12 months only (Canada), percentages with hSBA titres>=1:8 were 0-3%, 29-53%, 34
      36% and 10-29% against serogroups A, C, W-135 and Y respectively. CONCLUSIONS:
      Serogroup-specific bactericidal antibody wane following infant immunisation with
      MenACWY-CRM(197), most markedly against serogroup A. Best persistence against
      serogroup C is observed with MenC conjugate vaccine priming and MenACWY-CRM(197)
      at 12 months, compared to schedules using only MenACWY-CRM(197), with the
      potential for providing broader protection compared to monovalent MenC vaccines
      alone.

PMID- 22394993
TI  - Health outcomes of interest for evaluation in the Post-Licensure Rapid
      Immunization Safety Monitoring Program.
AB  - Active vaccine safety surveillance systems commonly use computerized diagnostic
      codes to identify potential health outcomes of interest. Evidence concerning the
      accuracy of these codes is variable, and few systematic reviews are available.
      This project's aim was to select a list of health outcomes of interest most
      suitable for evaluation in the Food and Drug Administration's Post-Licensure
      Rapid Immunization Safety Monitoring (PRISM) program. We conducted an expert
      elicitation process to develop the list. A comprehensive list of potential health
      outcomes of interest was formed based on input from a wide variety of vaccine
      safety experts. We then selected five panelists with senior leadership roles in
      vaccine safety from both within and outside the FDA. We elicited the experts'
      recommendations via a structured, iterative process that included an Internet
      assisted telephone conference call and formal voting procedures. The expert
      panelists identified several criteria as important in their choices, including
      clinical severity, public health importance, rare or uncommon incidence,
      relevance to two or more vaccines, and historical association with vaccines. The
      list of 24 outcomes chosen by the experts and refined by the FDA included ten
      neurologic outcomes, two circulatory system outcomes, and two musculoskeletal
      outcomes. The PRISM program plans to conduct a set of evidence reviews on the
      positive predictive value and other characteristics of existing computerized
      codes and algorithms to identify these health outcomes of interest.

PMID- 22394994
TI  - Vaccination and acute phase mediator production in chickens challenged with low
      pathogenic avian influenza virus; novel markers for vaccine efficacy?
AB  - Methods to determine vaccine efficacy of low pathogenic avian influenza (LPAI)
      isolates are limited in poultry because experimental infections with LPAI virus
      in specific pathogen free chickens rarely causes clinical disease. The most
      commonly used method to compare LPAI vaccine efficacy is to quantify viral
      shedding after challenge, but it is time and labor intensive. Therefore, we
      sought alternative methods to demonstrate vaccine efficacy, and examined whether
      vaccination of chickens affected the production of acute phase mediators in serum
      (e.g., alpha-1 acid glycoprotein, ovotransferrin and prostaglandin E(2))
      following challenge with homologous (A/Chicken/Hidalgo/232/94 H5N2) or
      heterologous (A/Chicken/167280-4/02 H5N3) LPAI isolates. Vaccination
      significantly reduced oropharyngeal viral shedding, and serum concentration of
      acute phase mediators, regardless of whether homologous or heterologous challenge
      viruses were used. Examining the expression of acute phase mediators post
      challenge may serve as additional markers to determine LPAI vaccine efficacy in
      chickens.

PMID- 22394995
TI  - Determining P-glycoprotein-drug interactions: evaluation of reconstituted P
      glycoprotein in a liposomal system and LLC-MDR1 polarized cell monolayers.
AB  - INTRODUCTION: P-Glycoprotein (ABCB1, MDR1) is a multidrug efflux pump that is a
      member of the ATP-binding cassette (ABC) superfamily. Many drugs in common
      clinical use are either substrates or inhibitors of this transporter.
      Quantitative details of P-glycoprotein inhibition by pharmaceutical agents are
      essential for assessment of their pharmacokinetic behavior and prevention of
      negative patient reactions. Cell-based systems have been widely used for
      determination of drug interactions with P-glycoprotein, but they suffer from
      several disadvantages, and results are often widely variable between
      laboratories. We aimed to demonstrate that a novel liposomal system employing
      contemporary biochemical methodologies could measure the ability of clinically
      used drugs to inhibit the P-glycoprotein pump. To accomplish this we compared
      results with those of cell-based approaches. METHODS: Purified transport
      competent hamster Abcb1a P-glycoprotein was reconstituted into a unilamellar
      liposomal system, Fluorosome-trans-pgp, whose aqueous interior contains
      fluorescent drug sensors. This provides a well-defined system for measuring P
      glycoprotein transport inhibition by test drugs in real time using rapid
      fluorescence-based technology. RESULTS: Inhibition of ATP-driven transport by
      Fluorosome-trans-pgp employed a panel of 46 representative drugs. Resulting IC50
      values correlated well (r2=0.80) with Kd values for drug binding to purified P
      glycoprotein. They also showed a similar trend to transport inhibition data
      obtained using LLC-MDR1 cell monolayers. Fluorosome-trans-pgp IC50 values were in
      agreement with published results of digoxin drug-drug interaction studies in
      humans. DISCUSSION: This novel approach using a liposomal system and fluorescence
      based technology is shown to be suitable to study whether marketed drugs and drug
      candidates are P-glycoprotein inhibitors. The assay is rapid, allowing a 7-point
      IC50 determination in <6 min, and requires minimal quantities of test drug. The
      method is amenable to robotics and offers a cost advantage relative to
      conventional cell-based assays. The well-defined nature of this assay also
      obviates many of the inherent complications and ambiguities of cell-based
      systems.

PMID- 22394996
TI  - Immunity and malignant mesothelioma: from mesothelial cell damage to tumor
      development and immune response-based therapies.
AB  - Malignant mesothelioma (MM) is a cancer with a high mortality rate and limited
      therapeutic options, typically presenting as a tumor in the serous membranes,
      most frequently in the pleura and the peritoneum rather than in the pericardium.
      There is much evidence that the immune system contributes to the biogenesis,
      growth and metastasis of MM through the unbalanced production of oxidants and
      cytokines, mesothelial cell DNA damage and the active support of MM
      neoangiogenesis and immunosuppression. Because classical therapeutic approaches
      are generally ineffective, novel immunological tools are being developed to
      target the immune cells infiltrating the MM foci and exploit the immune system to
      elicit an effective anti-tumor response. These therapies work by stimulating
      local inflammatory cells or transferring exogenously activated immunocompetent
      cells and by depleting MM-associated immunosuppressive clones to target the
      spontaneous specific immune responses against MM and to subvert MM-driven
      immunoediting. This review summarizes the recent evidence on the immune system
      mechanisms that support MM development and the novel therapeutic approaches for
      strengthening the immune system by MM immunotherapy that are currently being
      developed in both experimental models and clinical trials.

PMID- 22394998
TI  - The Chernobyl Tissue Bank: integrating research on radiation-induced thyroid
      cancer.
AB  - The only unequivocal radiological effect of the Chernobyl accident on human
      health is the increase in thyroid cancer in those exposed in childhood or early
      adolescence. Cancer is a complicated disease and it is unclear whether the
      mechanism by which radiation gives rise to cancer differs from that involved in
      the generation of cancers of the same type by other environmental stimuli. The
      Chernobyl Tissue Bank was established in response to the scientific interest in
      studying the molecular biology of thyroid cancer after Chernobyl to address this
      question. The project is supported by the governments of Ukraine and Russia, and
      financially supported (in total around US$3 million) by the European Commission,
      the National Cancer Institute of the USA and the Sasakawa Memorial Health
      Foundation of Japan. The project began collecting a variety of biological samples
      from patients on 1 October 1988, and has supplied material to 23 research
      projects in Japan, the USA and Europe. The establishment of the Chernobyl Tissue
      Bank has facilitated co-operation between these research projects and the
      combination of clinical and research data provides a paradigm for cancer research
      in the molecular biological age.

PMID- 22394997
TI  - Internet-based HIV and sexually transmitted infection testing in British
      Columbia, Canada: opinions and expectations of prospective clients.
AB  - BACKGROUND: The feasibility and acceptability of Internet-based sexually
      transmitted infection (STI) testing have been demonstrated; however, few programs
      have included testing for human immunodeficiency virus (HIV). In British
      Columbia, Canada, a new initiative will offer online access to chlamydia,
      gonorrhea, syphilis, and HIV testing, integrated with existing clinic-based
      services. We presented the model to gay men and other men who have sex with men
      (MSM) and existing clinic clients through a series of focus groups. OBJECTIVE: To
      identify perceived benefits, concerns, and expectations of a new model for
      Internet-based STI and HIV testing among potential end users. METHODS:
      Participants were recruited through email invitations, online classifieds, and
      flyers in STI clinics. A structured interview guide was used. Focus groups were
      audio recorded, and an observer took detailed field notes. Analysts then listened
      to audio recordings to validate field notes. Data were coded and analyzed using a
      scissor-and-sort technique. RESULTS: In total, 39 people participated in six
      focus groups. Most were MSM, and all were active Internet users and experienced
      with STI/HIV testing. Perceived benefits of Internet-based STI testing included
      anonymity, convenience, and client-centered control. Salient concerns were
      reluctance to provide personal information online, distrust of security of data
      provided online, and the need for comprehensive pretest information and support
      for those receiving positive results, particularly for HIV. Suggestions emerged
      for mitigation of these concerns: provide up-front and detailed information about
      the model, ask only the minimal information required for testing, give positive
      results only by phone or in person, and ensure that those testing positive are
      referred for counseling and support. End users expected Internet testing to offer
      continuous online service delivery, from booking appointments, to transmitting
      information to the laboratory, to getting prescriptions. Most participants said
      they would use the service or recommend it to others. Those who indicated they
      would be unlikely to use it generally either lived near an STI clinic or
      routinely saw a family doctor with whom they were comfortable testing.
      Participants expected that the service would provide the greatest benefit to
      individuals who do not already have access to sensitive sexual health services,
      are reluctant to test due to stigma, or want to take immediate action (eg,
      because of a recent potential STI/HIV exposure). CONCLUSIONS: Internet-based
      STI/HIV testing has the potential to reduce barriers to testing, as a complement
      to existing clinic-based services. Trust in the new online service, however, is a
      prerequisite to client uptake and may be engendered by transparency of
      information about the model, and by accounting for concerns related to
      confidentiality, data usage, and provision of positive (especially HIV) results.
      Ongoing evaluation of this new model will be essential to its success and to the
      confidence of its users.

PMID- 22394999
TI  - Drug shortages and ensuring the U.S. supply of needed pharmaceuticals.

PMID- 22395000
TI  - Peripheral vascular outcomes in the PLATO trial: update from the FDA ticagrelor
      complete response review.

PMID- 22395001
TI  - Preparing a scientific report to the general assembly on 'exposures due to the
      nuclear accident following the Great East-Japan earthquake and tsunami'.
AB  - At its 58th session in May 2011, the United Nations Committee on the Effects of
      Atomic Radiation (UNSCEAR) decided to carry out, once sufficient information was
      available, a full assessment of the levels of exposure and radiation risks
      attributable to the Fukushima accident. It envisages a preliminary document for
      consideration at its 59th session in May of 2012 and a more complete report for
      the 60th session of the Committee in 2013. This paper summarises the aims and
      objectives of the project, the scope, the working arrangements as well as the
      relation of the work to other activities.

PMID- 22395003
TI  - Is there a core neuropsychiatric phenotype in 22q11.2 deletion syndrome?
AB  - PURPOSE OF REVIEW: The aim is to discuss the clinical features of psychiatric
      illness in 22q11.2 deletion syndrome (22q11DS), and to review current evidence
      that a core neuropsychiatric phenotype could underlie the full spectrum of
      different presentations. RECENT FINDINGS: Individuals carrying the 22q11.2
      microdeletion are at risk for diverse psychiatric diagnoses across the lifespan,
      including schizophrenia in a significant minority, and anxiety or mood disorder
      in the majority. Symptoms and cognitive disruptions can be grouped into domains:
      attention-executive deficits, social-cognitive deficits, anxiety-affective
      dysregulation, and psychotic phenomena. These domains do not respect the
      boundaries of traditional diagnostic categories, and can be consistently
      recognized in children, adolescents and adults. There is early evidence that some
      symptom-domain disruptions may predict adult psychiatric morbidity. SUMMARY: If a
      core neuropsychiatric phenotype does exist in 22q11DS, its detection is likely to
      require dimensional assessment of subtle aspects of cognitive and emotional
      processing, not encompassed by current diagnostic systems. A core phenotype would
      account for disruptions across multiple symptom domains, directly reflecting
      genetic and neurobiological mechanisms. Relative severity of a core phenotype
      would predict risk for multiple psychiatric disorders, and could, therefore, be
      an important target for therapeutic and preventive interventions. A core
      phenotype meeting these criteria has not yet been defined for 22q11DS.

PMID- 22395004
TI  - Advances in research on the neurological and neuropsychiatric phenotype of
      Klinefelter syndrome.
AB  - PURPOSE OF REVIEW: Klinefelter syndrome, 47,XXY is the most common chromosomal
      aberration among men. It represents a naturally occurring human model for studies
      of both X-chromosome gene expression and potential androgen effects on brain
      development and function. The aim of this review is to combine available brain
      imaging and behavioral data to provide an overview of what we have learned about
      the neural underpinnings of cognitive, emotional and behavioral dysunctions in
      Klinefelter syndrome. RECENT FINDINGS: The behavioral phenotype of 47,XXY is
      characterized by language, executive and psychomotor dysfunction, as well as
      socioemotional impairment. The prevalence of schizophrenia, attention deficit
      hyperactivity disorder, autism spectrum disorders and affective regulation
      problems is increased. Neuroimaging studies of children and adults with
      Klinefelter syndrome syndrome show characteristic structural changes from typical
      individuals. There are increases in the grey matter volume of the sensorimotor
      and parietooccipital regions, as well as significant reductions in amygdala,
      hippocampal, insular, temporal and inferior-frontal grey matter volumes.
      Widespread white matter abnormalities have been revealed, with reductions in some
      areas (including anterior cingulate, bilaterally) but increases in others (such
      as left parietal lobe). Mechanisms underlying these developmental anomalies could
      include imbalance in gene dosage relative to typical men or women, as well as the
      potential consequence of endocrinological deficits. SUMMARY: Studies of
      Klinefelter syndrome could generate important information about the impact of
      anomalies in sex chromosome gene regulation on the development of cerebral grey
      and white matter and, ultimately, on human behavior.

PMID- 22395005
TI  - Current world literature.

PMID- 22395002
TI  - Conceptualizing neurodevelopmental disorders through a mechanistic understanding
      of fragile X syndrome and Williams syndrome.
AB  - PURPOSE OF REVIEW: The overarching goal of this review is to compare and contrast
      the cognitive-behavioral features of fragile X syndrome (FraX) and Williams
      syndrome and to review the putative neural and molecular underpinnings of these
      features. Information is presented in a framework that provides guiding
      principles for conceptualizing gene-brain-behavior associations in
      neurodevelopmental disorders. RECENT FINDINGS: Abnormalities, in particular
      cognitive-behavioral domains with similarities in underlying neurodevelopmental
      correlates, occur in both FraX and Williams syndrome including aberrant
      frontostriatal pathways leading to executive function deficits, and
      magnocellular/dorsal visual stream, superior parietal lobe, inferior parietal
      lobe, and postcentral gyrus abnormalities contributing to deficits in
      visuospatial function. Compelling cognitive-behavioral and neurodevelopmental
      contrasts also exist in these two disorders, for example, aberrant amygdala and
      fusiform cortex structure and function occurring in the context of contrasting
      social behavioral phenotypes, and temporal cortical and cerebellar abnormalities
      potentially underlying differences in language function. Abnormal dendritic
      development is a shared neurodevelopmental morphologic feature between FraX and
      Williams syndrome. Commonalities in molecular machinery and processes across FraX
      and Williams syndrome occur as well - microRNAs involved in translational
      regulation of major synaptic proteins; scaffolding proteins in excitatory
      synapses; and proteins involved in axonal development. SUMMARY: Although the
      genetic variations leading to FraX and Williams syndrome are different, important
      similarities and contrasts in the phenotype, neurocircuitry, molecular machinery,
      and cellular processes in these two disorders allow for a unique approach to
      conceptualizing gene-brain-behavior links occurring in neurodevelopmental
      disorders.

PMID- 22395007
TI  - Effect of a thioalkane capping layer on the first hyperpolarizabilities of gold
      and silver nanoparticles.
AB  - We have measured the first hyperpolarizabilities of thioalkane capped silver and
      gold metallic nanoparticles. The values found are beta(AgC 12-10 nm) = (2.10 +/-
      0.23) * 10(-26) esu for 10 nm diameter silver nanoparticles and beta(AuC 18-18
      nm) = (3.37 +/- 0.08) * 10(-26) esu for 18 nm diameter gold nanoparticles at the
      fundamental wavelength of 784 nm. By comparison to the corresponding values
      reported for citrate capped silver and gold metallic nanoparticles, after size
      corrections, decreases by factors of 4.3 and 6.5 respectively are observed. These
      decreases are tentatively attributed to the bonds formed between the gold and
      silver surface atoms and the sulfur atoms of the capping layer.

PMID- 22395008
TI  - [Patient involvement in the decision-making process in matters pertaining to
      health].

PMID- 22395009
TI  - [MiRNA in glioblastomas--potentials and limitations].

PMID- 22395010
TI  - [New glioma therapy using specific microRNAs].
AB  - Recent research has revealed the existence of a class of small non-coding RNAs,
      known as microRNAs. These microRNAs are deregulated in various cancers including
      gliomas. MicroRNAs have been suggested to be important in cancer stem cell
      biology and in proliferation and chemosensitivity of cancer cells. This makes
      microRNAs obvious targets for novel therapeutic strategies. In the present
      article we focus on the role of microRNAs in cancer cells and cancer stem cells
      as well as the possible therapeutic approaches exploiting this knowledge to
      improve future glioma therapy.

PMID- 22395011
TI  - [Generalized anxiety and depression should be diagnosis classified together].
AB  - Generalized anxiety disorder has a high prevalence in Denmark. From being an
      exclusion diagnosis to other anxiety disorders, the classification criteria have
      been made more strict in recent editions of international classifications.
      However, a marked comorbidity with depression questions the nosological status of
      generalized anxiety disorder. A review of psychiatric and psychological studies
      focusing on nosological aspects is presented, supporting that generalized anxiety
      disorder may be more appropriately classified together with depression as
      distress disorders.

PMID- 22395012
TI  - [Reduced salt intake and prevention of cardiovascular diseases].
AB  - In a Cochrane review on reduced dietary salt for the prevention of cardiovascular
      disease the results of one study showed that salt restriction increased
      mortality. In normotensive and hypertensive patients, who were analysed
      separately, an insignificant reduction in cardiovascular events was found. If the
      studies were analysed together, a significant reduction of cardiovascular events
      was found. The authors of the Cochrane review concluded that "there is still
      insufficient power to exclude clinically important effects of reduced dietary
      salt on in normotensives and hypertensives". We find that this conclusion is
      somewhat backwards. We consider salt restriction to be an important tool for
      improving population health.

PMID- 22395013
TI  - [Neurofibromatosis 1: pathogenesis and therapeutic strategies--a systematic
      review].
AB  - Neurofibromatosis 1 (NF1, von Recklinghausen's disease) is a dominantly inherited
      multi-organ disease defined primarily by cafe au lait patches and neurofibromas.
      NF1 predisposes to cancer and is associated with cognitive dysfunction and
      learning defects. In recent years, considerable progress has been made in the
      understanding of NF1 pathogenesis, not least based on studies of genetically
      engineered animal models. We present an overview of the most important recent
      findings and the related current efforts to develop novel therapeutic strategies.

PMID- 22395014
TI  - [Methylphenidate induced ST elevation acute myocardial infarction].
AB  - Adult attention deficit and hyperkinetic disorder (ADHD) is increasingly
      diagnosed and treated with methylphenidate. We present the case of an 20 year-old
      man, who was diagnosed with ADHD and suffered a ST elevation acute myocardial
      infarction due to coronary vasospasm related to an overdose, and subsequent
      episodes of myocardial injury due to the use and misuse of methylphenidate over a
      period of two years. We recommend an increased attention to the subscription of
      methylphenidate to patients, who are at risk of misuse and patients, who have a
      cardiovascular history.

PMID- 22395015
TI  - [Sublingual haematoma as a result of dysregulated peroral anticoagulant therapy].
AB  - We describe a case of spontaneous sublingual haematoma secondary to warfarin
      toxicity, leading to impending airway obstruction. The case was handled with the
      administration of vitamin K and fresh frozen plasma, and without invasive airway
      handling. Furthermore, we discuss the presentation of the condition and the signs
      of impending airway obstruction. Preferred management includes a safe airway and
      reversion of coagulopathy. The prognosis is good when treatment is prompt and
      correct.

PMID- 22395016
TI  - [Paranoid schizophrenic patient with unstable spinal fracture].
AB  - The misdiagnosis of somatic illness in the psychiatric population can have grave
      consequences. Somatic symptoms are easily overseen or misinterpreted and a
      careful history and examination is essential when approaching this group of
      patients. We report a case of a patient with a history of paranoid schizophrenia,
      who had her somatic symptoms misinterpreted as being of psychiatric origin. This
      misinterpretation gave rise to an admission to a psychiatric ward of a patient
      who actually presented with an unstable spinal fracture.

PMID- 22395017
TI  - [Lichen striatus with nail abnormality is a self-limiting condition].
AB  - A six year-old boy was referred with an asymptomatic linear rash on his left arm
      and a nail involvement of a fingernail on his left hand. Multiple small
      erythematous papules coalescing into a linear band extending to the thumb with
      nail abnormality were noted on the left arm. A diagnosis of lichen striatus was
      established clinically. The condition has spontaneous remission, although the
      course of the disease is prolonged when nail involvement exists. The condition is
      benign and there is no need to perform biopsy.

PMID- 22395018
TI  - [Good effect of plasmapheresis in fat embolism syndrome following bilateral
      fracture of tibia].
AB  - Fat embolism syndrome is a life-threatening condition, and early diagnosis and
      supportive treatment is important. In this case report plasmapheresis seemed to
      be of great importance.

PMID- 22395019
TI  - [Chronic HBV infection in a two year-old girl in spite of correct HBV vaccination
      after birth].
AB  - Our case story is about a two year-old girl who, despite full vaccination with
      neonatal hepatitis B immunoglobulin and hepatitis B vaccination and revaccination
      with hepatitis B vaccine at one, two and 12 months of age, got chronic hepatitis
      B presumably due to intrauterine mother-to-child transmission. Her mother was
      known to be HBsAg and HBeAg positive with genotype C and a viral load of one
      billion IU/ml. It is important that children with HBV infection are detected and
      seen in a special department. Post-vaccination screening of children from HBsAg
      positive mothers should be considered.

PMID- 22395021
TI  - Amorphous silicon nanocone array solar cell.
AB  - In the hydrogenated amorphous silicon [a-Si:H]-thin film solar cell, large
      amounts of traps reduce the carrier's lifetime that limit the photovoltaic
      performance, especially the power conversion efficiency. The nanowire structure
      is proposed to solve the low efficiency problem. In this work, we propose an
      amorphous silicon [a-Si]-solar cell with a nanocone array structure were
      implemented by reactive-ion etching through a polystyrene nanosphere template.
      The amorphous-Si nanocone exhibits absorption coefficient around 5 * 105/cm which
      is similar to the planar a-Si:H layer in our study. The nanostructure could
      provide the efficient carrier collection. Owing to the better carrier collection
      efficiency, efficiency of a-Si solar cell was increased from 1.43% to 1.77% by
      adding the nanocone structure which has 24% enhancement. Further passivation of
      the a-Si:H surface by hydrogen plasma treatment and an additional 10-nm intrinsic
      a-Si:H layer, the efficiency could further increase to 2.2%, which is 54%
      enhanced as compared to the planar solar cell. The input-photon-to-current
      conversion efficiency spectrum indicates the efficient carrier collection from
      300 to 800 nm of incident light.

PMID- 22395020
TI  - Validation of reference genes for expression analysis in the salivary gland and
      the intestine of Rhodnius prolixus (Hemiptera, Reduviidae) under different
      experimental conditions by quantitative real-time PCR.
AB  - BACKGROUND: Rhodnius prolixus is a blood-feeding insect that can transmit
      Trypanosoma cruzi and Trypanosoma rangeli to vertebrate hosts. Recently, genomic
      resources for invertebrate vectors of human pathogens have increased
      significantly, and R. prolixus has been one of the main species studied among the
      triatomines. However, the paucity of information on many of the fundamental
      molecular aspects of this species limits the use of the available genomic
      information. The present study aimed to facilitate gene expression studies by
      identifying the most suitable reference genes for the normalization of mRNA
      expression data from qPCR. RESULTS: The expression stability of five candidate
      reference genes (18S rRNA, GAPDH, beta-actin, alpha-tubulin and ribosomal protein
      L26) was evaluated by qPCR in two tissues (salivary gland and intestine) and
      under different physiological conditions: before and after blood feeding and
      after infection with T. cruzi or T. rangeli. The results were analyzed with three
      software programs: geNorm, NormFinder and BestKeeper. All of the evaluated
      candidate genes proved to be acceptable as reference genes, but some were found
      to be more appropriate depending on the experimental conditions. 18S, GAPDH and
      alpha-tubulin showed acceptable stability for studies in all of the tissues and
      experimental conditions evaluated. beta-actin, one of the most widely used
      reference genes, was confirmed to be one of the most suitable reference genes in
      studies with salivary glands, but it had the lowest expression stability in the
      intestine after insect blood feeding. L26 was identified as the poorest reference
      gene in the studies performed. CONCLUSIONS: The expression stability of the genes
      varies in different tissue samples and under different experimental conditions.
      The results provided by three statistical packages emphasize the suitability of
      all five of the tested reference genes in both the crop and the salivary glands
      with a few exceptions. The results emphasise the importance of validating
      reference genes for qRT-PCR analysis in R. prolixus studies.

PMID- 22395022
TI  - Patterns for four-allele population genetics model.
AB  - In this paper, we find and classify all existing patterns for a single-locus four
      allele population genetics models in continuous time. An existing pattern for a k
      allele model means a set of all coexisting asymptotically stable equilibria with
      respect to the flow defined by the system of equations p(i)=p(i)(r(i)
      r),i=1,...,k, where p(i) and r(i) are the frequency and marginal fitness of
      allele A(i), respectively, and r is the mean fitness of the population. It is
      well known that for the two-allele model there are only three existing patterns,
      depending on the relative fitness between the homozygotes and the heterozygote.
      For the three-allele model there are 14 existing patterns, and we shall show in
      this paper that for the four-allele model there are 117 existing patterns. We
      also describe the domains of attraction for coexisting asymptotically stable
      equilibria. The problem of finding existing patterns has been studied in the
      past, and it is an important problem because the results can be used to predict
      the long-term genetic makeup of a population. It should be pointed out that this
      continuous-time model is only an approximation to the corresponding discrete-time
      model. However, the set of equilibria and their stability properties are the same
      for the two models.

PMID- 22395023
TI  - Commentary: can mortality rates among adult antiretroviral therapy patients in
      Europe reach levels similar to those experienced in the general population?

PMID- 22395024
TI  - Fluorescence sensor for the quantification of unbound bilirubin concentrations.
AB  - BACKGROUND: Hyperbilirubinemia in jaundiced neonates is routinely assessed by use
      of total serum bilirubin. However, the unbound or free form (B(f)), not total
      bilirubin, crosses the blood-brain barrier and can be neurotoxic. Although the
      peroxidase-mediated oxidation of bilirubin can be used to measure plasma
      concentrations of B(f), this measurement is relatively complex and the assay is
      not routinely used. We describe a fluorescence sensor for quantifying B(f) in
      plasma. METHODS: Our method uses a mutated fatty acid binding protein labeled
      with the fluorescent molecule acrylodan (BL22P1B11), whose fluorescence is
      quenched upon binding bilirubin. Another configuration (BL22P1B11-Rh) was
      developed that uses BL22P1B11 together with the fluorophore rhodamine B, which
      responds by a change in the ratio of its fluorescence. RESULTS: The "B(f) probes"
      were calibrated with aqueous solutions of bilirubin and yielded similar bilirubin
      dissociation constants [K(d) = 16 (1.5) nmol/L]. We used the probes to determine
      B(f) concentrations in equilibrium with human serum albumin (HSA) and in human
      plasma samples supplemented with bilirubin. We obtained equivalent B(f) values in
      both systems, and the B(f) probe results were in agreement with the peroxidase
      assay. B(f) measurements revealed that bilirubin-HSA binding was well described
      by 2 sites with K(d) values of 15.4 (1) nmol/L and 748 (14) nmol/L. We measured
      B(f) concentrations in the range expected in jaundiced neonates with a mean CV of
      approximately 3%. CONCLUSIONS: The BL22P1B11-Rh probe provides accurate plasma
      sample B(f) concentrations with a single measurement, in 1 min with either a
      handheld B(f) meter or a laboratory fluorometer.

PMID- 22395026
TI  - Sometimes they come back: recurrent noncardiac right-to-left shunt after
      percutaneous patent foramen ovale closure.
AB  - : An increasing number of patients are being evaluated for percutaneous patent
      foramen ovale (PFO) closure to prevent recurrent cerebrovascular events, but
      debate still exists on therapeutic indications and off-label closure device
      implantation. Pulmonary arteriovenous fistulas (PAVFs) are a rare and
      heterogeneous malformation prevalently associated with Rendu-Osler-Weber
      syndrome, and may mimic PFO right-to-left shunt (RLS), leading to unnecessary
      interventions and in some cases to relapses. Residual shunt is increasingly being
      observed both after PFO closure and PAVF embolization, even at long-term follow
      up, with unclear clinical relevance. This instrumental and possibly therapeutic
      failure could lie in the presence of pulmonary microfistulas, either pre-existing
      or following the intervention. Hence, if RLS persists after optimal device
      placement and reasonable endothelialization time, the presence of a PAVF should
      be assumed and investigated; if RLS recurs after previous, negative echocontrast
      studies, presence of device-related complications or pulmonary microfistulas
      should be taken into consideration.

PMID- 22395025
TI  - Circulating microRNA miR-323-3p as a biomarker of ectopic pregnancy.
AB  - BACKGROUND: The use of serum human chorionic gonadotropin (hCG) and progesterone
      to identify patients with ectopic pregnancy (EP) has been shown to have poor
      clinical utility. Pregnancy-associated circulating microRNAs (miRNAs) have been
      proposed as potential biomarkers for the diagnosis of pregnancy-associated
      complications. This proof-of-concept study examined the diagnostic accuracy of
      various miRNAs to detect EP in an emergency department (ED) setting. METHODS:
      This study was a retrospective case-control analysis of 89 women who presented to
      the ED with vaginal bleeding and/or abdominal pain/cramping and received a
      diagnosis of viable intrauterine pregnancy (VIP), spontaneous abortion (SA), or
      EP. Serum hCG and progesterone concentrations were measured by immunoassays. The
      serum concentrations of miRNAs miR-323-3p, miR-517a, miR-519d, and miR-525-3p
      were measured with TaqMan real-time PCR. Statistical analysis was performed to
      determine the clinical utility of these biomarkers, both as single markers and as
      multimarker panels for EP. RESULTS: Concentrations of serum hCG, progesterone,
      miR-517a, miR-519d, and miR-525-3p were significantly lower in EP and SA cases
      than in VIP cases (P < 0.01). In contrast, the concentration of miR-323-3p was
      significantly increased in EP cases, compared with SA and VIP cases (P < 0.01).
      As a single marker, miR-323-3p had the highest sensitivity of 37.0% (at a fixed
      specificity of 90%). In comparison, the combined panel of hCG, progesterone, and
      miR-323-3p yielded the highest sensitivity (77.8%, at a fixed specificity of
      90%). A stepwise analysis that used hCG first, added progesterone, and then added
      miR-323-3p yielded a 96.3% sensitivity and a 72.6% specificity. CONCLUSIONS:
      Pregnancy-associated miRNAs, especially miR-323-3p, added substantial diagnostic
      accuracy to a panel including hCG and progesterone for the diagnosis of EP.

PMID- 22395027
TI  - Feasibility of strain and strain rate evaluation by two-dimensional speckle
      tracking in murine model of myocardial infarction:  comparison with tissue
      Doppler echocardiography.
AB  - BACKGROUND: Echocardiography has become a useful tool for serial evaluation of
      cardiac phenotype in mice. We aimed to examine the feasibility and
      reproducibility of advanced echocardiographic methods: two-dimensional speckle
      tracking (STE) and tissue Doppler echocardiography (TDE) in assessing strain and
      strain rate for analysis of myocardial infarction (MI) in a murine model.
      MATERIAL AND METHODS: We examined 10 anesthetized mice (of which five had MI and
      five had a normal heart) in parasternal short-axis view with the use of an M12L
      (14 MHz) transducer. The data were analyzed off-line by two independent
      investigators using standard echocardiographic parameters and radial strain and
      strain rate from TDE and STE. RESULTS: Reproducibility of analyzed parameters was
      high. A good correlation was found between strain and strain rate values measured
      from TDE and STE obtained by two investigators, reaching a correlation
      coefficient (r) from 0.94 to 0.99 for strain and from 0.90 to 0.98 for strain
      rate. The correlation coefficients between radial peak systolic TDE-dependent
      strain/strain rate vs. strain/strain rate measured from STE for anterior and
      posterior walls were: r=0.33 (P=0.35)/r=0.69 (P=0.03) and r=0.86
      (P=0.0012)/r=0.75 (P=0.01), respectively. Values of strain/strain rate reflected
      well to pathophysiology of MI in mice. CONCLUSIONS: We conclude that local
      myocardial function can be analyzed in mice using STE. This approach is rapid,
      reproducible and less time-consuming than TDE measurements in normal mice and in
      the MI model. STE alone, or combined with tissue Doppler imaging, is suitable for
      computer-assisted measurements of regional myocardial deformation in mice.

PMID- 22395028
TI  - Long-term independent predictors of positive response to cardiac
      resynchronization therapy.
AB  - AIMS: Cardiac resynchronization therapy (CRT) is currently considered an
      important breakthrough in the treatment of selected patients with refractory
      heart failure. However, long-term predictors of mortality, morbidity and time to
      recovery of ventricular function for those patients who respond positively to CRT
      remain poorly investigated. METHODS: This is a retrospective follow-up study
      involving one hospital. Between August 2004 and October 2008, 211 consecutive
      patients with refractory heart failure received a CRT device in the Cardiology
      Division of Ospedale Civile Maggiore in Verona. The clinical characteristics
      studied were age, sex, heart rhythm, left ventricular end-systolic volume/body
      surface area (LVESV/BSA), left ventricular ejection fraction, QRS duration, type
      of bundle-branch block, cause, New York Heart Failure Association functional
      class, pharmacological therapy and lead position. The objective of this study was
      to evaluate the effect of several baseline characteristics on long-term prognosis
      in heart failure patients treated with CRT. RESULTS: Nonischemic cause, left
      bundle-branch block and a basal LVESV/BSA of 106 ml/m or less were the only
      independent predictors of a positive response to CRT (P < 0.005). Additionally, a
      reduction in LVESV/BSA after CRT was associated both with increased survival and
      reduced rehospitalization for heart failure (P < 0.005). CONCLUSION: A better
      selection of patients on the basis of cause, type of bundle-branch block and
      basal LVESV/BSA can increase the number of patients that would benefit from CRT.

PMID- 22395029
TI  - Comparative analysis of hepatopulmonary shunt obtained from pretherapy 99mTc MAA
      scintigraphy and post-therapy 90Y Bremsstrahlung imaging in 90Y microsphere
      therapy.
AB  - INTRODUCTION: (99m)Tc macroaggregate albumin (MAA) scintigraphy is routinely used
      to estimate the hepatopulmonary shunt (HPS) of (90)Y microspheres because of
      their comparable average particle sizes (20-30 um). However, the MAA particle
      size can vary from 10 to 90 um. Therefore, HPS computed from (99m)Tc MAA
      scintigraphy may not accurately represent the HPS of (90)Y microspheres. In view
      of this, the present study was undertaken to investigate the accuracy of (99m)Tc
      MAA scintigraphy in estimating the HPS of (90)Y microspheres. MATERIALS AND
      METHODS: Nineteen sessions of transarterial radioembolization using (90)Y
      therasphere were carried out in 17 patients for hepatic malignancies (both
      primary and secondary). For each session of therapy, a pretherapeutic (99m)Tc MAA
      scintigraphy and post-therapeutic (90)Y Bremsstrahlung scintigraphy were
      performed. The HPSs obtained from these images were compared. RESULTS: The mean
      HPS fractions calculated from the pretherapeutic (99m)Tc MAA study and the post
      therapeutic (90)Y Bremsstrahlung images were 4.77 +/- 2.81 and 4.52 +/- 2.5%,
      respectively. The coefficient of correlation (r) was 0.96. CONCLUSION: (99m)Tc
      MAA scintigraphy accurately predicts the HPS of (90)Y microspheres.

PMID- 22395030
TI  - Risk factors for extensive skeletal muscle uptake in oncologic FDG-PET/CT for
      patients undergoing a 4-h fast.
AB  - OBJECTIVES: Postprandial insulin secretion causes extensive skeletal muscle
      accumulation (ESMA) of fluorine-18 fluorodeoxyglucose (FDG), which adversely
      affects visual interpretation of FDG-PET/CT. We investigated factors related to
      ESMA despite a fast of at least 4 h. METHODS: A total of 3595 patients underwent
      FDG-PET/CT following a fast for at least 4 h. Among them, patients exhibiting
      ESMA affected by postprandial insulin and sex-matched and age-matched individuals
      without ESMA as controls were analysed. The following factors were compared: BMI,
      plasma glucose, presence of diabetes including suspected diabetes (DM-IS),
      presence of diabetes excluding suspected diabetes, insulin therapy, approximate
      volume of gastric food residue estimated by CT and residue including water.
      Multivariate analysis was performed among cases and controls made to fast
      identically for 4-5 h to assess independent risk factors. RESULTS: Overall, 44
      patients with ESMA and 100 controls were identified. The BMI of cases (22.0+/
      3.0) was not significantly different from that of controls (21.5+/-2.9). Plasma
      glucose was significantly higher in cases (134.9+/-44.0 vs. 113.6+/-31.4 mg/dl;
      P=0.0050). Cases had a significantly higher proportion of DM-IS, presence of
      diabetes excluding suspected diabetes, insulin therapy, gastric food residue and
      residue including water (P<0.0001, P=0.0074, 0.0011, 0.0008 and 0.039,
      respectively). Logistic regression analysis among 29 cases and 100 controls who
      had undergone 4-5 h fasting revealed that DM-IS and gastric food residue were
      independent risk factors for ESMA with odds ratios of 5.14 (P=0.0006) and 5.39
      (P=0.0014), respectively. CONCLUSION: It would be preferable to fast for a longer
      time, especially for patients with glucose intolerance, and avoid heavy meals to
      reduce gastric residue.

PMID- 22395031
TI  - Bile acid malabsorption and SeHCAT: the 'Cinderella' will be going to the Nuclear
      Medicine Ball!

PMID- 22395032
TI  - Understanding and fighting cancer cachexia syndrome:  can PET help?

PMID- 22395033
TI  - Measuring SeHCAT retention:  the use of a collimated gamma camera.

PMID- 22395034
TI  - Molecular imaging of brain tumors with 18F-DOPA PET and PET/CT.
AB  - The objective of this study was to give an overview of the potential clinical
      utility of [18F]-L-dihydroxyphenylalanine (18F-DOPA) PET and PET/CT for imaging
      of brain tumors. Review articles and reference lists were used to supplement the
      search findings. 18F-DOPA has been investigated as a PET tracer for primary brain
      tumors, metastases of somatic cancer, and evaluation of relapse of pathology in
      patients with brain tumor after surgery and/or radiotherapy on the basis of
      enhanced cell proliferation. Available studies have provided encouraging
      preliminary results for diagnosis of brain tumors and relapse after
      surgery/radiotherapy. In the brain, excellent discrimination between tumor and
      normal tissue can be achieved because of the low physiological uptake of 18F-DOPA
      and the high ratio between tumor and normal hemispheric tissue. Information on
      evaluation of brain metastases is limited but encouraging. PET and PET/CT with
      18F-DOPA are useful in diagnosing primary brain tumors and should be recommended
      in the diagnosis of relapse of disease after surgical treatment and/or
      radiotherapy. Semiquantitative analysis could improve diagnosis while correlative
      imaging with MRI is essential. Limits are due to low knowledge of potential
      pitfalls.

PMID- 22395035
TI  - Myocardial perfusion scintigraphy in Taiwan from 2005 to 2009.
AB  - OBJECTIVE: To analyze the utilization of myocardial perfusion scintigraphy (MPS)
      in Taiwan within the universal healthcare system, the National Health Insurance
      (NHI) from 2005 to 2009, and to compare with European surveys. METHODS: On the
      basis of Taiwan's National Health Insurance Research Database of 2005-2009, a
      retrospective population-based analysis was conducted. Descriptive statistics
      were provided on the frequencies of and distributions in the utilization of MPS
      during the period. In addition, correlation analysis was applied to identify
      correlated factors in the utility of MPS. RESULTS: The annual number of MPS
      procedures performed was estimated to be 76 448 on average in 2005-2009 and 3361
      per million population (pmp) over the period. The frequency increased by 45%,
      from 3008 pmp in 2005 to 4371 pmp in 2009, with an annual increase rate of 11.9%.
      The expenditure on MPS increased by 51%, from 12.3 million USD in 2005 to 18.55
      million USD in 2009, with an annual increase rate of 12.9%. The average cost of
      identifying a coronary artery disease (CAD) case with MPS was 248 USD, with a
      2.6% annual increase rate. Most patients were more than 50 years old when they
      received the MPS examination, whereas inpatients were much older. In addition,
      most of the MPS practices were performed in medical centers and regional
      hospitals, although an apparent increase was seen in district hospitals on
      outpatients. As a consequence, the rate of CAD diagnoses by MPS decreased over
      time. CONCLUSION: The numbers, frequencies, and expenses of MPS practices have
      increased in Taiwan during the period 2005-2009, especially for outpatients. The
      application rate of MPS in Taiwan was higher than that in Europe, likely because
      of the high accessibility to MPS procedures within the NHI system. This
      experience in Taiwan may serve as a reference for illustrating the trends in the
      use of MPS procedures in countries with a universal healthcare system.

PMID- 22395036
TI  - WHO's public health agenda in response to the Fukushima Daiichi nuclear accident.
AB  - The World Health Organization (WHO) has responded to the 2011 East-Japan
      earthquake and tsunami through the three levels of its decentralised structure.
      It has provided public health advice regarding a number of issues relating to
      protective measures, potassium iodide use, as well as safety of food and drinking
      water, mental health, travel, tourism, and trade. WHO is currently developing an
      initial health risk assessment linked to a preliminary evaluation of radiation
      exposure around the world from the Fukushima Daiichi nuclear accident. Lessons
      learned from this disaster are likely to help future emergency response to multi
      faceted disasters.

PMID- 22395038
TI  - The lifetime risk of total hip and knee arthroplasty: results from the UK general
      practice research database.
AB  - OBJECTIVE: To estimate the lifetime risk of undergoing primary total hip (THR) or
      knee (TKR) replacement in the UK. METHOD: A Population-based cohort study of
      25,845 patients who had undergone a THR and 23,260 patients who had undergone a
      TKR between 1991 and 2006, using data from the UK General Practice Research
      Database. RESULTS: The estimated mortality-adjusted lifetime risk of THR at age
      50 for the year 2005 was 11.6% (95% CI: 11.1, 12.1) for women and 7.1% (95% CI:
      6.7, 7.5) for men. For TKR the risks were 10.8% (95% CI: 10.3, 11.3) for women
      and 8.1% (95% CI: 7.6, 8.5) for men. Between 1991 and 2006, the lifetime risk of
      THR at age 50 rose from 4.0% (95% CI: 3.5, 4.4) to 11.1% (95% CI: 10.6, 11.6) for
      women and for men from 2.2% (95% CI: 1.8, 2.5) to 6.6% (95% CI: 6.2, 7.0). Over
      the same period, for TKR the risk for women increased from 2.9% (95% CI: 2.6,
      3.3) to 10.6% (95% CI: 10.1, 11.1) and for men from 1.8% (95% CI: 1.5, 2.2) to
      7.7% (95% CI: 7.3, 8.2). CONCLUSION: The lifetime risk of undergoing THR or TKR
      is estimated to be substantially less than the risk of developing symptomatic hip
      or knee osteoarthritis. For the knee, the difference between these risk estimates
      is particularly wide. The reasons for the size of these differences are not
      clear, and further work is needed to quantify the extent of latent demand for
      these cost-effective and established interventions among the population with
      symptomatic osteoarthritis of the hip or knee.

PMID- 22395037
TI  - Side differences of thigh muscle cross-sectional areas and maximal isometric
      muscle force in bilateral knees with the same radiographic disease stage, but
      unilateral frequent pain - data from the osteoarthritis initiative.
AB  - OBJECTIVE: To determine whether anatomical thigh muscle cross-sectional areas
      (MCSAs) and strength differ between osteoarthritis (OA) knees with frequent pain
      compared with contra-lateral knees without pain, and to examine the correlation
      between MCSAs and strength in painful vs painless knees. METHODS: Forty-eight
      subjects (31 women; 17 men; age 45-78 years) were drawn from 4,796 Osteoarthritis
      Initiative (OAI) participants, in whom both knees displayed the same radiographic
      stage (KLG2 or 3), one with frequent pain (most days of the month within the past
      12 months) and the contra-lateral one without pain. Axial MR images were used to
      determine MCSAs of extensors, flexors and adductors at 35% femoral length (distal
      to proximal) and in two adjacent 5 mm images. Maximal isometric extensor and
      flexor forces were used as provided from the OAI database. RESULTS: Painful knees
      showed 5.2% lower extensor MCSAs (P=0.00003; paired t-test), and 7.8% lower
      maximal extensor muscle forces (P=0.003) than contra-lateral painless knees.
      There were no significant differences in flexor forces, or flexor and adductor
      MCSAs (P>0.39). Correlations between force and MCSAs were similar in painful and
      painless OA knees (0.44<r<0.66). CONCLUSIONS: Knees with frequent pain
      demonstrate lower MCSAs and force of the quadriceps (but not of other thigh
      muscles) compared with contra-lateral knees without knee pain with the same
      radiographic stage. Frequent pain does not appear to affect the correlations
      between MCSAs and strength in OA knees. The findings suggest that quadriceps
      strengthening exercise may be useful in treating symptomatic knee OA.

PMID- 22395039
TI  - Delineating the impact of obesity and its relationship on recovery after total
      joint arthroplasties.
AB  - OBJECTIVE: The primary aim of this study was to determine the impact of obesity
      in predicting short and long-term pain relief and functional recovery in total
      joint arthroplasty (TJA) either as an independent risk factor or a factor
      mediated by two chronic conditions associated with obesity-cardiac disease and
      diabetes mellitus. METHOD: A prospective observational study of 520 patients with
      primary joint arthroplasties. Pain and functional outcomes were evaluated with
      the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index within
      a month of surgery and then 6 months and 3 years post-operatively. Obesity,
      cardiac disease and diabetes mellitus were examined as potential risk factors for
      poor recovery. Patients were classified into four groups based on body mass index
      (BMI): (normal<25.0 kg/m(2); overweight 25.0-29.9 kg/m(2); obese Class 1 30.0
      34.9 kg/m(2); severe obese Class 2&3 35.0 >= kg/m(2)). Linear mixed models for
      each joint type (hip and knee arthroplasty) were developed to examine the pattern
      of recovery and the effect of obesity. RESULTS: Ninety-nine (19%) patients were
      severely obese, 127 (24%) had cardiac disease and 58 (11%) had diabetes mellitus.
      Baseline pain and functional scores were similar regardless of BMI
      classification. Severe obesity was a significant risk factor for worse pain and
      functional recovery at 6 months but no longer at 3 years following total hip and
      knee arthroplasty. Cardiac disease predicted a slower recovery after hip
      arthroplasty. No significant interactions existed between obesity and cardiac
      disease or diabetes mellitus. DISCUSSION: Severe obesity is an independent risk
      factor for slow recovery over 3 years for both hip and knee arthroplasties.

PMID- 22395040
TI  - Predicting the acidity constant of a goethite hydroxyl group from first
      principles.
AB  - Accurate predictions of the acid-base behavior of hydroxyl groups at mineral
      surfaces are critical for understanding the trapping of toxic and radioactive
      ions in soil samples. In this work, we apply ab initio molecular dynamics (AIMD)
      simulations and potential-of-mean-force techniques to calculate the pK(a) of a
      doubly protonated oxygen atom bonded to a single Fe atom (Fe(I)OH(2)) on the
      goethite (101) surface. Using formic acid as a reference system, pK(a) = 7.0 is
      predicted, suggesting that isolated, positively charged groups of this type are
      marginally stable at neutral pH. Similarities and differences between AIMD and
      the more empirical multi-site complexation methodology are highlighted,
      particularly with respect to the treatment of hydrogen bonding with water and
      proton sharing among surface hydroxyl groups. We also highlight the importance of
      an electronic structure method that can accurately predict transition metal ion
      properties for goethite pK(a) calculations.

PMID- 22395042
TI  - Current world literature.

PMID- 22395041
TI  - Clinical evidence that V456A is a Cystic Fibrosis causing mutation in South
      Asians.
AB  - BACKGROUND: Cystic Fibrosis (CF) genotypes in South Asians are variable with a
      decreased incidence of Delta F508 and an increased incidence of novel mutations.
      The objective of this study is to provide clinical evidence that V456A, a novel
      mutation in South Asian Cystic Fibrosis patients, can cause significant lung
      disease. METHODS: We extracted clinical data from a retrospective chart review of
      2 CF patients of South Asian descent. RESULTS: Patient 1, a 10 year and 11 month
      old Pakistani female at her initial clinic visit, required multiple
      hospitalizations for bronchiectasis and pulmonary infections. She was pancreatic
      sufficient but had slow weight gain. Genetic testing revealed that she is
      homozygous for the CFTR V456A mutation. Patient 2, an Indian female diagnosed
      with CF on newborn screening, is compound heterozygous for V456A/R709X. She had
      slow weight gain with BMI ranging from 12.9 to 13.4 kg/m(2) from 3 to 5 years of
      age and was 14.2 kg/m(2) at 6 years of age. At 6 years of age, pulmonary function
      tests revealed mild lung disease with FVC of 71%, FEV(1) of 75%, FEF(25-75) of
      119%, and FEV(1)/FVC of 86% predicted. Sputum cultures were intermittently
      positive for Staphylococcus aureus and Haemophilus influenza. CONCLUSIONS: We
      provide evidence that V456A can cause significant pulmonary disease in South
      Asian Cystic Fibrosis patients.

PMID- 22395044
TI  - Intraoperative prediction of postoperative flap outcome using the near-infrared
      fluorophore methylene blue.
AB  - Methylene blue (MB) is a near-infrared fluorophore that provides a stable visual
      map of skin perfusion after intravenous injection. We explored the capability of
      MB to predict submental flap postoperative outcome using a single intraoperative
      measurement. Submental flaps were created in N = 15 pigs and imaged using the
      FLARE imaging system immediately after surgery and at 72 hours. Using the first 3
      pigs, optimal MB dosing was found to be 2.0 mg/kg. Training and validation sets
      of 6 pigs each were then used for receiver operating characteristic analysis. In
      the training set, a contrast-to-background ratio (CBR) threshold of 1.24 provided
      the highest sensitivity and specificity to predict tissue necrosis at 72 hours.
      In the validation set, this threshold provided a prediction sensitivity of 95.3%
      and a specificity of 98.0%. We demonstrate that a single intraoperative near
      infrared measurement can predict submental flap outcome at 72 hours.

PMID- 22395045
TI  - Fingertip replantation without venous anastomosis.
AB  - BACKGROUND: Replantation of amputated fingertips is a technical challenge, as
      many salvage procedures fail because no suitable vein in the fingertip is
      available for anastomosis. In this study, we examined our experience in fingertip
      replantation in cases without venous anastomosis with our established fingertip
      replantation treatment protocol. METHODS: Between August 2002 and August 2010, a
      retrospective study examined all patients who had undergone fingertip
      replantation at Chang-Gung Memorial Hospital. All the patients (n = 24) suffered
      from complete digital amputations at or distal to the interphalangeal joint of
      the thumb, or distal to distal interphalangeal joint of the fingers. A total of
      30 fingertips that were salvaged by microsurgical anastomosis of the digital
      arteries but not of digital veins were included in this study. On satisfactory
      arterial anastomosis, a 2-mm incision was made over the fingertip with a number
      11 Scalpel blade, and 0.1 to 0.2 mL heparin (5000 IU/mL) was injected
      subcutaneously around the incision immediately and once per day thereafter to
      ensure continuous blood drainage from the replanted fingertip. None of the
      replanted nail plate was removed, and no medical leeches were used. The perfusion
      of the replanted digits and patient's hemoglobin level were closely monitored.
      The wound bleeding was maintained until physiologic venous outflow was restored.
      RESULTS: Of 30 fingertips, 27 (90%) replanted fingertips survived. The average
      length needed for maintaining external bleeding by chemical leech was 6.8 days
      (range, 5-10 days). Twelve patients (including a 2-year-old child) received blood
      transfusions. The average amount of blood transfusion in the 23 adults was 4.0
      units (range, 0-16 units) for each patient or 3.29 units (range, 0-14 units) for
      each digit. A 2-year-old child received 100 mL blood transfusion or 50 mL for
      each digit. CONCLUSIONS: This study showed that a protocol that promotes
      controlled bleeding from the fingertip is essential to achieve consistent high
      success rates in fingertip replantation. The protocol is safe and reliable, as it
      avoids the use of medical leeches and the removal of nail plate from the
      replanted finger. However, full informed patient consent must include the
      potential need for transfusion and extended hospital stay.

PMID- 22395046
TI  - Closure of the radial forearm donor site using a local hatchet flap: analysis of
      45 consecutive cases.
AB  - BACKGROUND: The radial forearm free flap (RFFF) is widely used in reconstructive
      surgery. Traditional donor-site closure by grafting may be associated with
      significant aesthetic and functional morbidity. We report our experience with
      primary closure using a local hatchet flap. METHODS: In all, 45 consecutive
      patients who underwent RFFF reconstruction in the head and neck during an 8-year
      period were retrospectively assessed with regards to their donor-site morbidity.
      RESULTS: The mean age of the patients was 54, with 23 being female. The mean RFFF
      area harvested was 37.7 cm; mean width, 7.6 cm (5.5-11 cm); and mean length, 4.7
      cm (3.5-6.5 cm). All patients had their donor site closed primarily utilizing a
      local hatchet flap. At the time of follow-up, there were 33 surviving patients,
      of which 31 patients were available for assessment. CONCLUSIONS: We recommend
      this technique of primary closure of the RFFF donor site: it is well tolerated by
      the patient, with good cosmesis and is associated with no discernable functional
      morbidity.

PMID- 22395047
TI  - Accelerated wound closure in a diabetic mouse model after exposure to
      phenanthrenequinone.
AB  - BACKGROUND: Reactive oxygen species (ROS) have been shown to be important in
      wound healing by promoting angiogenesis (also mentioned by Ushio-Fukai and
      Nakamura). Likewise ROS have been implicated by toxicological studies as a
      primary mechanism of air pollution-associated morbidity. We sought to determine
      how exposure to a reactive diesel exhaust chemical (phenanthrenequinone [PQ]),
      which promotes formation of ROS and is considered an air pollutant, would affect
      wound healing. Since wound healing is compromised in diabetic (db) individuals,
      we examined the effects of PQ on wound healing in a db mouse model. METHODS: db
      mice consumed PQ-containing chow for a short period (2 weeks) before wounding and
      through generations. Wound closure rates and wound vascularization were evaluated
      10 days after wounding. The effects of PQ on endothelial cell proliferation and
      ROS generation in vitro were also measured. RESULTS: db mice exposed to short
      term PQ and PQ-exposed first-generation db mice demonstrated the highest closure
      rates, significantly better than control db mice (P < 0.05). Furthermore, a
      higher concentration of PQ in sera of db mice coincides with the higher rate of
      closure. PQ was also shown to produce ROS in cell culture and stimulate
      endothelial cell proliferation at nanomolar concentrations. Second- and third
      generation db mice exposed to PQ did not show improved wound healing.
      CONCLUSIONS: This study suggests that the free radical-generating air pollutant
      PQ enhances wound closure in the db mouse model possibly by stimulating
      angiogenesis, as suggested by in vitro results. We speculate that PQ may increase
      oxidation levels systemically and therefore help modulate inflammation at the
      wound site. Alternatively, antioxidant mechanisms recruited for wound healing may
      interfere with PQ metabolism and elimination as it accumulates in sera.
      Generational resistance to improve wound healing in PQ-exposed db mice could also
      be due to disturbances in metabolism caused by continuous exposure. In either
      case, these results introduce a new perspective on the effects of air pollution
      on wound healing.

PMID- 22395048
TI  - Modified rotational bowel vaginoplasty after total pelvic exenteration.
AB  - Vaginal reconstructive options commonly include the use of split-thickness skin
      grafts or intestinal conduits. When a colonic segment is chosen, the sigmoid
      colon is favored because of its location, size, and durability. When
      circumstances preclude the use of sigmoid colon and a colonic conduit is
      preferred, creative means of mobilization are required. This article describes a
      case and technique utilizing the descending colon in a tension-free vaginoplasty.

PMID- 22395049
TI  - Think small: nanotechnology for plastic surgeons.
AB  - The purpose of this article is to introduce the topic of nanotechnology to
      plastic surgeons and to discuss its relevance to medicine in general and plastic
      surgery in particular. Nanotechnology will be defined, and some important
      historical milestones discussed. Common applications of nanotechnology in various
      medical and surgical subspecialties will be reviewed. Future applications of
      nanotechnology to plastic surgery will be examined. Finally, the critical field
      of nanotoxicology and the safe use of nanotechnology in medicine and plastic
      surgery will be addressed.

PMID- 22395050
TI  - Extratemporal facial paralysis.
AB  - PURPOSE: This report summarizes our experience in the management of extratemporal
      facial paralysis with a variety of reconstructive techniques and explores those
      parameters which are considered to be useful in achieving better outcomes.
      METHODS: In all, 56 patients with extratemporal facial paralysis were studied.
      All the patients had a mean follow-up of 5 years (standard deviation: 3.5). Video
      evaluation was performed by 3 independent assessors at the required follow-up
      intervals. RESULTS: The final median score for the partial facial paralysis group
      was significantly higher (4.175) compared with the complete facial paralysis
      (3.3), P = 0.007. In this series, the only other factor that appeared to
      influence the final outcome was the denervation time and not the age group, type
      of facial nerve injury, or method of repair. CONCLUSION: The concept of dynamic
      panfacial reconstruction with an individual and tailored to patient's needs
      approach is demonstrated in all and particularly in bilateral cases.

PMID- 22395051
TI  - The ubiquitin/SUMO pathway and radial ray deficiency syndromes.
AB  - Protein regulation is the function of several pathways and enzyme systems in the
      human body. One of these pathways is the ubiquitin/SUMO pathway. The author has
      noted that almost all known syndromes of radial ray deficiency are related to
      this pathway. In this article, these syndromes are reviewed with special
      attention to their relationship with the ubiquitin/SUMO pathway. This opens a new
      insight into the pathogenesis of radial ray deficiency syndromes.

PMID- 22395052
TI  - Subcutaneous tissue expansion and subsequent subpectoral implantation for breast
      reconstruction in Asian patients: safety and outcome.
AB  - Asian women are generally thin with smaller breasts. The objective was to
      investigate the outcomes for patients who underwent 2-stage breast reconstruction
      using subcutaneous expansion followed by subpectoral implantation. Between 2003
      and 2008, 22 patients underwent subcutaneous expansion and subsequent submuscular
      implantation for 23 breast reconstructions. Mean age was 44.6 +/- 7.0 years. The
      outcome was assessed with a pain visual analog scale, a questionnaire, and the
      cosmesis. Mean expansion volume was 350.3 +/- 80.8 mL. Mean implant size was
      306.7 +/- 84.6 mL. The complication rate was 8.6%, 13.0% in first and second
      stages. Mean pain scale was 2 +/- 1.4. At a mean follow-up of 42.5 +/- 18 months,
      patient's satisfaction was 3.2 +/- 0.9. Overall shape of the reconstructed breast
      was rated as 2.8 +/- 0.5. Subcutaneous expansion with subsequent subpectoral
      implantation is feasible and reliable in low body mass index, nonsmoking,
      nonradiated patients with small and projective breasts.

PMID- 22395053
TI  - Calcium channel blockers reduce the effects of cigarette smoking on peripheral
      nerve ischemia/reperfusion injury.
AB  - The efficacy of calcium channel blockers in reducing the effects of
      ischemia/reperfusion (I/R) injury in animals subjected to cigarette smoke was
      examined. In this study, 40 rats were divided into 4 groups. Groups A, B, and C
      received a controlled cigarette smoke exposure for 14 days, following which all
      animals underwent a standardized sciatic nerve I/R procedure. One sciatic nerve
      was isolated, and the femoral artery was occluded for 3 hours followed by
      reperfusion. Group B received verapamil (20 mg/kg/d). Group C received nifedipine
      (10 mg/kg/d). Mean sciatic function index (SFI) was significantly higher in
      nonsmoking than smoking animals, and the sciatic function index of group B
      (verapamil) and group C (nifedipine) was significantly greater than group A
      (smoking). Mean malondialdehyde at day 28 in group A was 0.96 +/- 0.14 compared
      with 0.74 +/- 0.11 in the nonsmoking group (P = 0.03), and the mean
      malondialdehyde in the nifedipine group was significantly greater than in group A
      (P = 0.05). Histologic injury scores were not significantly different among
      groups exposed to smoke. Smoking was associated with slower recovery following
      peripheral nerve I/R injury, but calcium channel blockers were shown to
      ameliorate these effects.

PMID- 22395054
TI  - A comparison of levobupivacaine and levobupivacaine-tramadol combination in
      bilateral infraorbital nerve block for postoperative analgesia after nasal
      surgery.
AB  - BACKGROUND: Our aim in this study was to investigate the effect of
      levobupivacaine and a levobupivacaine + tramadol combination on postoperative
      analgesia in intraoperative nerve block under standard general anesthetic.
      METHODS: Forty-five patients undergoing outpatient nasal surgery under general
      anesthesia were randomized into 3 groups. Group L: 0.25% levobupivacaine, group
      T: 0.25% levobupivacaine and 50 mg tramadol, group S: normal saline solution; 2
      mL of each being injected into the infraorbital foramen. Intraoperative
      hemodynamic changes were recorded. Verbal numeric rating scale (NRS) values were
      checked at 30 minutes and 1, 2, 8, and 12 hours postoperatively, and the need for
      rescue analgesic treatment in the first 12 hours of all patients was recorded.
      Also antiemetic drug requirement and side effects (nausea, edema, erythema,
      hematoma, and sedation) were recorded. RESULTS: At 30 minutes and 1 hour
      postoperatively, NRS pain scores were lower in group T than in group S (P <
      0.0001, P = 0.01, respectively). NRS pain score was lower in group T compared
      with group L at 1 hour postoperatively (P = 0.01). Effective analgesia time (sec)
      in the control group (142.67 +/- 77.31) was shorter than levobupivacaine (240 +/-
      96.39) and levobupivacaine added to tramadol groups (277 +/- 11.60) (P < 0.05).
      Additional analgesic requirement in the control group was higher than the other 2
      groups in early postoperative period (P < 0.05). CONCLUSIONS: Bilateral
      infraorbital nerve block with 0.25% levobupivacaine is an effective, reliable,
      and simple technique in the treatment of postoperative pain in nasal surgery. In
      addition, the addition of tramadol as an adjuvant to local anesthetics in this
      technique is safe.

PMID- 22395055
TI  - Surgical implantation of chronic neural electrodes for recording single unit
      activity and electrocorticographic signals.
AB  - The success of long-term electrophysiological recordings often depends on the
      quality of the implantation surgery.  Here we provide useful information for
      surgeons who are learning the process of implanting electrode systems.  We
      demonstrate the implantation procedure of both a penetrating and a surface
      electrode.  The surgical process is described from start to finish, including
      detailed descriptions of each step throughout the procedure.  It should also be
      noted that this video guide is focused towards procedures conducted in rodent
      models and other small animal models.  Modifications of the described procedures
      are feasible for other animal models.

PMID- 22395056
TI  - Radiation protection principles.
AB  - The International Commission on Radiological Protection (ICRP) recommends a
      system of radiological protection that is in use worldwide. This paper describes
      the elements of that system, identifying the central assumptions and principles.
      A key assumption for protection at low doses is that there is a simple
      proportionate relationship between increments in dose and increments in risk. The
      system focuses on changes to the level of peoples' exposure, recommending that
      any change is justified (i.e., the benefit is clear) and protection is then
      optimised (i.e., improvement in dose reduction is promoted when possible and
      reasonable). In doing so, the system considers the amenability of the source of
      exposure to control and the acceptability of the exposure to individuals or
      society.

PMID- 22395057
TI  - Epitaxial deposition of silver ultra-fine nano-clusters on defect-free surfaces
      of HOPG-derived few-layer graphene in a UHV multi-chamber by in situ STM, ex situ
      XPS, and ab initio calculations.
AB  - The growth of three-dimensional ultra-fine spherical nano-particles of silver on
      few layers of graphene derived from highly oriented pyrolytic graphite in ultra
      high vacuum were characterized using in situ scanning tunneling microscopy (STM)
      in conjunction with X-ray photoelectron spectroscopy. The energetics of the Ag
      clusters was determined by DFT simulations. The Ag clusters appeared spherical
      with size distribution averaging approximately 2 nm in diameter. STM revealed the
      preferred site for the position of the Ag atom in the C-benzene ring of graphene.
      Of the three sites, the C-C bridge, the C-hexagon hollow, and the direct top of
      the C atom, Ag prefers to stay on top of the C atom, contrary to expectation of
      the hexagon-close packing. Ab initio calculations confirm the lowest potential
      energy between Ag and the graphene structure to be at the exact site determined
      from STM imaging.

PMID- 22395058
TI  - Theory and research.

PMID- 22395060
TI  - Bacterial colonization of pancreatic stents: incidental finding or cause for
      concern?

PMID- 22395061
TI  - Predicting Helicobacter pylori eradication: how to teach an old dog new tricks!

PMID- 22395062
TI  - Nonalcoholic fatty liver disease: multimodal treatment options for a
      pathogenetically multiple-hit disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) has emerged as a significant public
      health problem. Besides the liver, NAFLD is also associated with increased
      cardiovascular and overall morbidity and mortality. NAFLD warrants intensive
      research, because no treatment has been established as yet. This may be partly
      attributed to the fact that the majority of the relative clinical trials have a
      monotherapeutic direction. However, the multifactorial pathogenesis of NAFLD may
      probably direct clinical trials to a combined therapeutic approach. The aim of
      this review is to provide a description of the multifactorial pathogenesis of
      NAFLD and type II diabetes mellitus-NAFLD interplay, and to summarize the
      therapeutic trials focusing on the combined NAFLD treatment, providing a link
      between the multiple-hit pathogenesis and the multimodal treatment of NAFLD
      patients. A diabetes-like therapeutic approach for NAFLD is finally proposed.

PMID- 22395064
TI  - Prevalence and related factors of irritable bowel syndrome among middle-school
      students in areas affected by Wenchuan Earthquake: an epidemiological study.

PMID- 22395063
TI  - A rapid continuous-real-time 13C-urea breath test for the detection of
      Helicobacter pylori in patients after partial gastrectomy.
AB  - INTRODUCTION: Before the development of efficient medications for peptic ulcer
      disease many patients were treated surgically by partial gastrectomy. The
      pathogenetic role of Helicobacter pylori was also not known yet. Some of these
      patients may therefore still harbor H. pylori in their remnant stomach as a
      carcinogenic agent for gastric cancer. This could be even more relevant for
      patients who were operated for tumors in the stomach. The efficacy of the urea
      breath test (UBT) is not clear in this population. AIMS: To study the prevalence
      of H. pylori and to evaluate the sensitivity and specificity of the continuous
      UBT (BreathID) in postgastrectomized patients in Israel. In this system, the pH
      of the stomach is lowered by the addition of citric acid that may be beneficial
      in the smaller and more alkalic stomach. METHODS: We compared retrospectively the
      results of our continous UBT with a rapid urease test (RUT) and the histology in
      all our patients who underwent gastroscopy for any clinical indication, and had a
      history of partial gastrectomy during the years 2002 to 2010. Only patients in
      whom H. pylori was tested by all the 3 methods during the same day were included
      in the study. We identified 76 such patients older than 18 years and performed a
      statistical analysis of all possibly related clinical data. The 3 methods were
      compared with each other. RESULTS: H. pylori was positive in 14/76 (18.4%)
      patients when histology was considered as the gold standard method. The positive
      predictive value of the continuous UBT and the RUT was 0.64 and 0.35,
      respectively. The negative predictive value was high by both the methods, 0.92
      and 0.95, respectively. Weight loss was correlated with positivity for H. pylori
      (P=0.032) and a longer gastric stump was marginally related to H. pylori
      (P=0.071). There was no difference for H. pylori positivity between patients with
      Billroth I or Billroth II operations. Prevalence of H. pylori was not lower in
      patients who had partial gastrectomy several years earlier. CONCLUSIONS: The
      prevalence of H. pylori is considerable even several years after partial
      gastrectomy. The BreathID is reliable to exclude H. pylori after partial
      gastrectomy. The positive predictive value of the UBT is not very high but better
      than the RUT. We suggest that all positive patients found by the breath test
      should be treated. Our results support the view that alternative noninvasive
      methods, such as the stool antigen test should be further studied and compared
      with the BreathID in larger populations.

PMID- 22395065
TI  - Neurospora mrc1 homologue is involved in replication stability and is required
      for normal cell growth and chromosome integrity in mus-9 and mus-21 mutants.
AB  - Stalled replication forks easily collapse and such structures can induce DNA
      strand breaks or toxic recombination products. Therefore, factors involved in
      stabilization of replication should be important for genome integrity. In our
      previous study, loss of both ATM and ATR homologues was shown to cause growth
      defects and chromosome instability in Neurospora crassa. To elucidate the
      relationships between these defects and replication instability, we focused on
      one of the viable replication factors, mrc1. We identified an mrc1 homologue from
      the N. crassa genome database. The mrc1 disruptant was sensitive to the
      replication inhibitor hydroxyurea (HU) and delayed restart of the cell cycle from
      HU treatment. Importantly, HU treatment induced histone H2A phosphorylation in
      the mrc1 mutant but not in the wild type. Furthermore, the HU-induced H2A
      phosphorylation was completely dependent on the ATM homologue mus-21, and
      dysfunction of mus-21 increased HU sensitivity of the mrc1 mutant. These results
      indicate that Neurospora mrc1 is important for stabilization of replication forks
      and that loss of mrc1 causes activation of the DNA damage checkpoint.
      Unexpectedly, loss of mrc1 did not affect cell growth, but the deletion of mrc1
      reduced hyphal growth speed and conidia viability in the mus-9 and mus-21
      mutants. The mrc1 mus-9 and mrc1 mus-21 double mutants also showed accumulation
      of micronuclei, which is a typical marker of chromosome instability. These
      results imply that activation of the checkpoint pathway can protect cells from
      instability of DNA replication caused by loss of mrc1.

PMID- 22395066
TI  - IAEA activities related to radiation biology and health effects of radiation.
AB  - The IAEA is involved in capacity building with regard to the radiobiological
      sciences in its member states through its technical cooperation programme.
      Research projects/programmes are normally carried out within the framework of
      coordinated research projects (CRPs). Under this programme, two CRPs have been
      approved which are relevant to nuclear/radiation accidents: (1) stem cell
      therapeutics to modify radiation-induced damage to normal tissue, and (2)
      strengthening biological dosimetry in IAEA member states.

PMID- 22395067
TI  - Hysteroscopic treatment of the cesarean-induced isthmocele in restoring
      infertility.
AB  - PURPOSE OF REVIEW: To review the treatments of the cesarean-induced isthmocele in
      restoring infertility, associated techniques, and the risks of complications
      associated with their use. RECENT FINDINGS: Isthmocele is a reservoir-like pouch
      defect on the anterior wall of the uterine isthmus located at the site of a
      previous cesarean delivery scar. The flow of menstrual blood through the cervix
      may be slowed by the presence of isthmocele, as the blood may accumulate in the
      niche because of the presence of fibrotic tissue, causing pelvic pain in the
      suprapubic area. Moreover, persistence of the menstrual blood after menstruation
      in the cervix may negatively influence the mucus quality and sperm quality,
      obstruct sperm transport through the cervical canal, interfere with embryo
      implantation, leading to secondary infertility. The removal of the local inflamed
      tissue may be performed by laparoscopic, combined laparoscopic-vaginal, or
      vaginal surgery, and operative hysteroscopy, a minimally invasive approach to
      improve symptoms and restore fertility. SUMMARY: Isthmocele occurs after cesarean
      section, a common method of delivery and one of the most frequent surgical
      procedures, so that its upward incidence appears likely to continue in the near
      future. Because of its minimal invasiveness, resectoscopy may be the better
      choice for treatment, yielding good therapeutic results.

PMID- 22395068
TI  - Has fertility declined in recent decades?
AB  - PURPOSE OF REVIEW: Over the last decade, a number of studies have been published
      on whether fertility has declined. The purpose of this article is to review the
      trends in fertility rates and assess how biological, behavioural, social and
      environmental factors affect fertility rates. RECENT FINDINGS: The average total
      fertility rate (TFR) in Europe is down to 1.5 children per woman, and the
      perceived ideal family size is also declining. Factors impacting on lower
      fertility include the instability of modern partnerships and value changes.
      Fertility depends on natural fecundity but also on a number of behavioural
      determinants, such as culture, society, economic conditions, living standards and
      other similar background determinants on individual reproductive behaviour.
      SUMMARY: Increasing use of infertility treatment and a decline in demographic
      fertility in some countries have raised concern whether human fecundity is
      declining or has declined over time. The downward trend in fecundity articulated
      on numerous occasions over the last decade, seems unsubstantiated as the
      forecasting agencies such as the United Nations and Eurostat are likely to be
      right in their medium variant assumption that TFR levels in most countries will
      rise to 1.5 or above in the decades ahead.

PMID- 22395069
TI  - Bone formation in TiO2 bone scaffolds in extraction sockets of minipigs.
AB  - The osteoconductive capacity of TiO(2) scaffolds was investigated by analysing
      the bone ingrowth into the scaffold structure following their placement into
      surgically modified extraction sockets in Gottingen minipigs. Non-critical size
      defects were used in order to ensure sufficient bone regeneration for the
      evaluation of bone ingrowth to the porous scaffold structure, and sham sites were
      used as positive control. Microcomputed tomographic analysis revealed 73.6+/
      11.1% of the available scaffold pore space to be occupied by newly formed bone
      tissue, and the volumetric bone mineral density of the regenerated bone was
      comparable to that of the native cortical bone. Furthermore, histological
      evidence of vascularization and the presence of bone lamellae surrounding some of
      the blood vessels were also observed within the inner regions of the scaffold,
      indicating that the highly interconnected pore structure of the TiO(2) scaffolds
      supports unobstructed formation of viable bone tissue within the entire scaffold
      structure. In addition, bone tissue was found to be in direct contact with 50.0+/
      21.5% of the TiO(2) struts, demonstrating the good biocompatibility and
      osteoconductivity of the scaffold material.

PMID- 22395070
TI  - Cyclin D2 in the basal process of neural progenitors is linked to non-equivalent
      cell fates.
AB  - Asymmetric cell division plays an indispensable role during corticogenesis for
      producing new neurons while maintaining a self-renewing pool of apical
      progenitors. The cellular and molecular determinants favouring asymmetric
      division are not completely understood. Here, we identify a novel mechanism for
      generating cellular asymmetry through the active transportation and local
      translation of Cyclin D2 mRNA in the basal process. This process is regulated by
      a unique cis-regulatory sequence found in the 3' untranslated region (3'UTR) of
      the mRNA. Unequal inheritance of Cyclin D2 protein to the basally positioned
      daughter cell with the basal process confers renewal of the apical progenitor
      after asymmetric division. Conversely, depletion of Cyclin D2 in the apically
      positioned daughter cell results in terminal neuronal differentiation. We
      demonstrate that Cyclin D2 is also expressed in the developing human cortex
      within similar domains, thus indicating that its role as a fate determinant is
      ancient and conserved.

PMID- 22395073
TI  - [To best celebrate a long road which has been travelled, it is so good to have a
      longer one to go].

PMID- 22395071
TI  - Ebola virus entry requires the host-programmed recognition of an intracellular
      receptor.
AB  - Ebola and Marburg filoviruses cause deadly outbreaks of haemorrhagic fever.
      Despite considerable efforts, no essential cellular receptors for filovirus entry
      have been identified. We showed previously that Niemann-Pick C1 (NPC1), a
      lysosomal cholesterol transporter, is required for filovirus entry. Here, we
      demonstrate that NPC1 is a critical filovirus receptor. Human NPC1 fulfills a
      cardinal property of viral receptors: it confers susceptibility to filovirus
      infection when expressed in non-permissive reptilian cells. The second luminal
      domain of NPC1 binds directly and specifically to the viral glycoprotein, GP, and
      a synthetic single-pass membrane protein containing this domain has viral
      receptor activity. Purified NPC1 binds only to a cleaved form of GP that is
      generated within cells during entry, and only viruses containing cleaved GP can
      utilize a receptor retargeted to the cell surface. Our findings support a model
      in which GP cleavage by endosomal cysteine proteases unmasks the binding site for
      NPC1, and GP-NPC1 engagement within lysosomes promotes a late step in entry
      proximal to viral escape into the host cytoplasm. NPC1 is the first known viral
      receptor that recognizes its ligand within an intracellular compartment and not
      at the plasma membrane.

PMID- 22395074
TI  - [Editorial 1/1982. The reason for this journal].

PMID- 22395075
TI  - [Editorial 1/1999. Assistenza infermieristica e ricerca (AIR): what has
      changed?].

PMID- 22395072
TI  - Lysophospholipid presentation by CD1d and recognition by a human Natural Killer T
      cell receptor.
AB  - Invariant Natural Killer T (iNKT) cells use highly restricted alphabeta T cell
      receptors (TCRs) to probe the repertoire of lipids presented by CD1d molecules.
      Here, we describe our studies of lysophosphatidylcholine (LPC) presentation by
      human CD1d and its recognition by a native, LPC-specific iNKT TCR. Human CD1d
      presenting LPC adopts an altered conformation from that of CD1d presenting
      glycolipid antigens, with a shifted alpha1 helix resulting in an open A' pocket.
      Binding of the iNKT TCR requires a 7-A displacement of the LPC headgroup but
      stabilizes the CD1d-LPC complex in a closed conformation. The iNKT TCR CDR loop
      footprint on CD1d-LPC is anchored by the conserved positioning of the CDR3alpha
      loop, whereas the remaining CDR loops are shifted, due in part to amino-acid
      differences in the CDR3beta and Jbeta segment used by this iNKT TCR. These
      findings provide insight into how lysophospholipids are presented by human CD1d
      molecules and how this complex is recognized by some, but not all, human iNKT
      cells.

PMID- 22395076
TI  - [Editorial 1986. Rituals and myths in nursing care].

PMID- 22395077
TI  - [Rituals, myths and fashions of nursing care: a follow-up after 30 years and new
      risky trends].
AB  - Nearly 30 years ago in an editorial rituals and myths of the nursing profession
      were presented and discussed, to identify the most recurrent and their meaning
      and implications for the nursing profession. Some of the old rituals have been
      cleared bur replaced by new ones. Others, are still present, although some
      situations largely improved, still need further improvement. A list of practices
      borderline between organization, evidences and natural evolution of culture and
      habits is presented and implications and some future developments discussed.
      Nursing, like medicine, needs (and will never get rid of) rituals and myths: the
      importance is the capacity to avoid a critical obedience and exercise a critical
      appraisal.

PMID- 22395078
TI  - [A review of nursing and multidisciplinary journals for nurses in Italy].
AB  - General nursing journals are only three and 6 specialistic nursing journals (for
      intensive care, neurology, neurosurgery and psychiatric nurses, paediatric
      nurses, diabetes cardiology and perioperative nurses) are published in Italy.
      Several Italian journals include in their mission a special focus to nurses and
      nursing care. The main journals are presented and described and some reflections
      are offered on the future challenges for Italian nursing journals.

PMID- 22395079
TI  - [Research studies published in Assistenza infermieristica e ricerca from 1991 to
      2011].
AB  - OBJECTIVE: The research studies published on Assistenza Infermieristica e Ricerca
      along the last 21 years were analysed to identify main trends. METHOD: Research
      articles were extracted and each was classified according to the main area,
      authors, place of origin, design. RESULTS: The number of research papers is
      progressively increasing and represents 50% of the papers published in 2006-2001.
      Most papers are focused on clinical practice and deal with issues relevant for
      the practice such as symptom control, organization or problems of elderly and
      frail populations. The number of experimental-quasi-experimental studies is
      limited (12%) but the variety of research designs increased in the last 5 years,
      with qualitative and validation studies. CONCLUSIONS: Although the number good
      quality research papers is increasing, most studies are monocentric and research
      needs to be incremented and promoted.

PMID- 22395080
TI  - [30 years of multicentre and collaborative projects].
AB  - A thirty years long story of Assistenza Infermieristica e Ricerca, of the
      research projects launched and of the research networks implemented, is the
      occasion for an assessment of results achieved and of the future strategies. The
      journal achieved in getting started several successful projects (a rather unique
      achievement for a research journal, not only at national level). Most projects
      were companion studies of clinical trials but also independent epidemiological
      studies and a clinical trial were organized and published. The most challenging
      aspect is the ability to keep networks "alive" and able to continue to make and
      propose research.

PMID- 22395081
TI  - [Technology is changing: is the continuing professional development also
      changing?].
AB  - This paper considers the impact of the new information environment on the
      scientific communication. Reading behavior changes: today, we browse, scan,
      watch, receive an impression of something. The new reading habits are not simply
      determined by the new tools; they are rather influenced by the need to produce
      and share data and information, using personalized and mobile devices. Also the
      content formats change: researchers, clinicians, and nurses produce texts,
      figures, tables, photos, videos, tweets, blog posts and they share them to
      readers that have to collect, appraise, recombine and - most importantly -
      contextualize the information. This "continuous partial production" is consistent
      with a "continuous partial utilization" of data; this is a risk, but it is also
      an opportunity. On the one side, we risk a self-referential, individualized
      learning process; on the other side, we can enjoy the extraordinary chance to
      build a "shared learning environment", able to give a comprehensive solution to
      the challenges experienced by the health systems. Medical journals survive as
      valuable media to organize data and information; the new social web tools should
      support the traditional publishing patterns, to enhance the sharing of
      information, to help the appraisal of data, and to move forward new communities
      of learners.

PMID- 22395082
TI  - [Nurses in dialogue with the world].
AB  - The two sections International Observatory and Face to face were started with the
      aim to open a window on the outside world (economical, cultural, history of
      people and countries, sentinel events of violation of human rights). The guiding
      thread of the contribution published was the "beauty" thus poetry, human rights,
      theatre and literature crossed each other in this session, to remind that
      medicine (and the outside world) is not only evidence but also grey, in
      expressible areas. This different look at problems should remind that health care
      workers should be not only competent technicians but also explorers and experts
      of new pathways to promote the take on charge and respect of human rights.

PMID- 22395085
TI  - Does good+good=better? A pilot study on the effect of combining hedonically
      valenced smells and images.
AB  - Responses to affective stimuli are usually studied in just one sensory system at
      a time. However, this is rarely the way they are experienced. We were interested
      in how combining affective stimuli of similar intensities across two sensory
      modalities (smell and vision) would affect both behavioral responses (ratings)
      and psychophysiological responses (skin conductance). We studied this using
      olfactory stimuli delivered birhinally while the subjects viewed affectively
      laden scenes on a computer screen. Bilateral skin conductance recordings were
      taken throughout. Subjects rated the pleasantness of the images that they were
      viewing. We found a particularly salient effect of unpleasant smells, which
      enhanced the pleasantness ratings of certain images and also the skin conductance
      responses to unpleasant images.

PMID- 22395084
TI  - Brain hypoactivation, autonomic nervous system dysregulation, and gonadal
      hormones in depression: a preliminary study.
AB  - The comorbidity of major depressive disorder (MDD) and cardiovascular disease
      (CVD) is among the 10th leading cause of morbidity and mortality worldwide. Thus,
      understanding the co-occurrence of these disorders will have major public health
      significance. MDD is associated with an abnormal stress response, manifested in
      brain circuitry deficits, gonadal dysfunction, and autonomic nervous system (ANS)
      dysregulation. Contribution of the relationships between these systems to the
      pathophysiology of MDD is not well understood. The objective of this preliminary
      study was to investigate, in parallel, relationships between HPG-axis
      functioning, stress response circuitry activation, and parasympathetic reactivity
      in healthy controls and women with MDD. Using fMRI with pulse oximetry [from
      which we calculated the high frequency (HF) component of R-R interval variability
      (HF-RRV), a measure of parasympathetic modulation] and hormone data, we studied
      eight women with recurrent MDD in remission and six controls during a stress
      response paradigm. We demonstrated that hypoactivations of hypothalamus,
      amygdala, hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex
      (OFC), and subgenual ACC were associated with lower parasympathetic cardiac
      modulation in MDD women. Estradiol and progesterone attenuated group differences
      in the effect of HF-RRV on hypoactivation in the amygdala, hippocampus, ACC, and
      OFC in MDD women. Findings have implications for understanding the relationship
      between mood, arousal, heart regulation, and gonadal hormones, and may provide
      insights into MDD and CVD risk comorbidity.

PMID- 22395086
TI  - Cortical brain imaging by adaptive filtering of NIRS signals.
AB  - This paper presents an online brain imaging framework for cognitive tasks
      conducted with functional near-infrared spectroscopy (fNIRS). The measured signal
      at each channel is regarded as the output from a linear system with unknown
      coefficients. The unknown coefficients are estimated by using the recursive least
      squares estimation (RLSE) method. The validity of the estimated parameters is
      tested using the t-statistics. Contrary to the classical approach that is offline
      and applies the same preprocessing scheme to all channels, the proposed RLSE
      method for a linear model formulation provides an independent robust adaptive
      process for individual channels. The experiments carried out with two fNIRS
      instruments (continuous-wave and frequency-domain) have verified the potential of
      the proposed methodology which can facilitate a prompt medical diagnostics by
      providing real-time brain activation maps.

PMID- 22395087
TI  - BDNF as an effect modifier for gender effects on pain thresholds in healthy
      subjects.
AB  - BDNF is an important marker of neuronal plasticity. It has also been associated
      with pain processing. Increased BDNF levels are observed in chronic pain
      syndromes. In order to understand the role of BDNF associated with other factors
      such as gender on experimental pain we aimed to determine whether experimental
      heat or pressure pain threshold is correlated with brain derived neurotrophic
      factor (BDNF) level, gender and age. Heat pain threshold and pressure pain
      threshold were measured in 49 healthy volunteers (27 females). The multivariate
      linear regression models (on heat and pressure pain thresholds) revealed a
      significant effect of gender (p=0.001 for both models), serum BDNF (p<0.004 for
      both models) and interaction between BDNF and gender (<0.001 for both models). In
      fact, when adjusting for BDNF levels and age, heat and pressure pain thresholds
      were significantly reduced in women as compared to men (p<0.001 for both models).
      These effects were not observed when gender was analyzed alone. These finding
      suggests that experimental heat and pressure pain threshold is gender-related and
      BDNF dependent. In fact BDNF has a facilitatory effect on pain threshold in
      females but has an opposite effect in males; supporting the notion that BDNF is
      an effect modifier of the gender effects on pain threshold in healthy subjects.

PMID- 22395088
TI  - Glial activation in a pilocarpine rat model for epileptogenesis: a morphometric
      and quantitative analysis.
AB  - In this work we examined the correlation between long-term glial resilience and
      slow epileptogenesis using the pilocarpine-insult rat model. We assessed,
      quantitatively and morphometrically, glial fibrillary acidic protein (GFAP)
      expression and cell densities in hippocampus in a dose-response manner 2, 4 and 8
      weeks after the pilocarpine insult. GFAP changes were correlated with
      observations on microglial activation. We used a commonly applied epileptogenic
      pilocarpine dose (380mg/kg) and its fractions of 1/10, 1/4 and 1/2. GFAP
      expression evaluated at 2 weeks revealed dose-dependent cytoskeletal hypertrophy
      and loss of GFAP+ cell densities in hippocampus. At 4-week timepoint, recoveries
      of the above mentioned parameters were observed in all groups, except for the
      full dose group in which the astrocytic hypertrophy reached the highest level,
      while its density dropped to the lowest level. Strong and localized microgliosis
      revealed by CD11b immunoreactivity was observed in hilus in the full dose group
      at 2- and 4-, persisting at 8-week timepoints. Through changing pattern analysis,
      we conclude that the loss of astroglial resilience is likely to be a determining
      factor for spontaneous recurrent seizure onset.

PMID- 22395089
TI  - Aberrant functional connectivity of cortico-basal ganglia circuits in major
      depression.
AB  - There is considerable evidence of functional abnormalities of the cortico-basal
      ganglia circuitry in affective disorders. However, it has been unknown whether
      this represented primary pathology within these circuits or altered activation as
      a result of aberrant input from other brain regions. The aim of this study was to
      test the hypothesis that cortico-basal ganglia circuit dysfunction represents
      primary pathology in unipolar depression. Eighteen male subjects with recurrent
      unipolar depression and eighteen controls without psychiatric illness were
      studied using functional MRI and functional connectivity analyses. All unipolar
      subjects were unmedicated and without current psychiatric comorbidity. Compared
      to controls, unipolar subjects exhibited altered connectivity between bilateral
      subcortical components of the circuitry (putamen-thalamus) and left hemisphere
      input and output components. Results provided evidence that functional
      abnormalities of these circuits represent primary pathology. Further, we found
      that age of onset but not duration of illness impacts circuit function. These
      findings suggest that the cortico-basal ganglia circuitry is likely one of
      several loci of primary pathology in major depression. Additionally, early age of
      onset is associated with greater circuit abnormality and as such may impact
      clinical characteristics and/or treatment response through a mechanism of
      decreasing functional connectivity of some circuit segments. Finally, altered
      cortico-basal ganglia circuit connectivity with cortical regions (anterior
      cingulate, inferior frontal gyrus and sensorimotor) may contribute to the
      emotional dysregulation, impaired emotional recognition and psychomotor symptoms
      associated with unipolar illness.

PMID- 22395090
TI  - Reporting of short-term clinical outcomes after esophagectomy: a systematic
      review.
AB  - OBJECTIVE: This review summarizes reporting of complications of esophageal cancer
      surgery. BACKGROUND: Accurate assessment of morbidity and mortality after surgery
      for cancer is essential to compare centers, allow data synthesis, and inform
      clinical decision-making. A lack of defined standards may distort clinically
      relevant treatment effects. METHODS: Systematic literature searches identified
      articles published between 2005 and 2009 reporting morbidity and mortality after
      esophagectomy for cancer. Data were analyzed for frequency of complication
      reporting and to check whether outcomes were defined and classified for severity
      and whether a validated system for grading complications was used. Information
      about reporting outcomes adjusting for baseline risk factors was collated, and a
      descriptive summary of the results of included outcomes was undertaken. RESULTS:
      Of 3458 abstracts, 224 full papers were reviewed and 122 were included (17
      randomized trials and 105 observational studies), reporting outcomes of 57,299
      esophagectomies. No single complication was reported in all papers, and 60
      (60.6%) did not define any of the measured complications. Anastomotic leak was
      the most commonly reported morbidity, assessed in 80 (80.1%) articles, defined in
      28 (28.3%), but 22 different descriptions were used. Five papers (5.1%)
      categorized morbidity with a validated grading system. One hundred fifteen papers
      reported postoperative mortality rates, 25 defining the term using 10 different
      definitions. In-hospital mortality was the most commonly used term for
      postoperative death, with 6 different interpretations of this phrase. Eighteen
      papers adjusted outcomes for baseline risk factors and 60 presented baseline
      measures of comorbidity. CONCLUSIONS: Outcome reporting after esophageal cancer
      surgery is heterogeneous and inconsistent, and it lacks methodological rigor. A
      consensus approach to reporting clinical outcomes should be considered, and at
      the minimum it is recommended that a "core outcome set" is defined and used in
      all studies reporting outcomes of esophageal cancer surgery. This will allow
      meaningful cross study comparisons and analyses to evaluate surgery.

PMID- 22395091
TI  - An integrated proteomics and metabolomics approach for defining oncofetal
      biomarkers in the colorectal cancer.
AB  - OBJECTIVE: The present study was designed to search for potential diagnostic
      biomarkers in the serum of colorectal cancer (CRC). BACKGROUND: CRC is the third
      most common cancer worldwide, and its prognosis is poor at early stages. A panel
      of novel biomarkers is urgently needed for early diagnosis of CRC. METHODS: An
      integrated proteomics and metabolomics approach was performed to define oncofetal
      biomarkers in CRC by protein and metabolite profiling of serum samples from CRC
      patients, healthy control adults, and fetus. The differentially expressed
      proteins were identified by a 2-D DIGE (2-Dimensional Difference Gel
      Electrophoresis) coupled with a Finnigan LTQ-based proteomics approach.
      Meanwhile, the serum metabolome was analyzed using gas chromatography-mass
      spectrometry integrated with a commercial mass spectral library for peak
      identification. RESULTS: Of the 28 identified proteins and the 34 analyzed
      metabolites, only 5 protein spots and 6 metabolites were significantly increased
      or decreased in both CRC and fetal serum groups compared with the healthy adult
      group. Data from supervised predictive models allowed a separation of 93.5% of
      CRC patients from the healthy controls using the 6 metabolites. Finally,
      correlation analysis was applied to establish quantitative linkages between the 5
      individual metabolite 3-hydroxybutyric acid, L-valine, L-threonine, 1
      deoxyglucose, and glycine and the 5 individual proteins MACF1, APOH, A2M, IGL@,
      and VDB. Furthermore, 10 potential oncofetal biomarkers were characterized and
      their potential for CRC diagnosis was validated. CONCLUSION: The integrated
      approach we developed will promote the translation of biomarkers with clinical
      value into routine clinical practice.

PMID- 22395092
TI  - Randomized, controlled, blinded trial of Tisseel/Tissucol for mesh fixation in
      patients undergoing Lichtenstein technique for primary inguinal hernia repair:
      results of the TIMELI trial.
AB  - OBJECTIVE: Test the hypothesis that fibrin sealant mesh fixation can reduce the
      incidence of postoperative pain/numbness/groin discomfort by up to 50% compared
      with sutures for repair of inguinal hernias using the Lichtenstein technique.
      BACKGROUND: Inguinal hernia repair is the most common procedure in general
      surgery, thus improvements in surgical techniques, which reduce the burden of
      undesirable postoperative outcomes, are of clinical importance. METHODS: A
      randomized, controlled, patient- and evaluator-blinded study (Tissucol/Tisseel
      for MEsh fixation in LIchtenstein hernia repair [TIMELI]; trial NCT00306839) was
      conducted among patients eligible for Lichtenstein repair of uncomplicated
      unilateral primary inguinal small-medium sized hernia. Patients were subject to
      mesh fixation with either fibrin sealant or sutures. Main outcome measures were
      visual analogue scale (VAS) assessments for "pain," "numbness," and "groin
      discomfort" on a scale of 0 = best and 100 = worst outcome. The primary endpoint
      was a composite that evaluated the prevalence of chronic disabling complications
      (VAS score >30 for pain/numbness/groin discomfort) at 12 months after surgery.
      RESULTS: In total, 319 patients were randomized between January 2006 and April
      2007 (159 fibrin sealant, 160 sutures). At 12 months, the prevalence of 1 or more
      disabling complication was significantly lower in the fibrin sealant group than
      in the sutures group (8.1% vs 14.8%; P = 0.0344). Less pain was reported in the
      fibrin sealant group than in the sutures group at 1 and 6 months (P = 0.0132; P =
      0.0052), as reflected by a lower proportion of patients using analgesics in the
      fibrin group over the study duration (65.2% vs 79.7%; P = 0.0009). Only 3 of 316
      patients (0.9%) experienced recurrence. The incidences of wound-healing
      complications and other adverse events were comparable between groups.
      CONCLUSIONS: Fibrin sealant for mesh fixation in Lichtenstein repair of small
      medium sized inguinal hernias is well tolerated and reduces the rate of
      pain/numbness/groin discomfort by 45% relative to sutures without increasing
      hernia recurrence (NCT00306839).

PMID- 22395094
TI  - A reversible fluorescent DNA logic gate based on graphene oxide and its
      application for iodide sensing.
AB  - A simple and reliable fluorescent DNA logic gate is developed by utilizing
      graphene oxide as a signal transducer and mercury ions and iodide as mechanical
      activators.

PMID- 22395093
TI  - Multicenter study for optimal categorization of extramural tumor deposits for
      colorectal cancer staging.
AB  - OBJECTIVE: This study aimed to determine the optimal categorization of extramural
      tumor deposits lacking residual lymph node (LN) structure (EX) in colorectal
      cancer staging. BACKGROUND: The TNM classification system categorizes EX on the
      basis of their contour characteristics (the contour rule). METHODS: We conducted
      a multicenter, retrospective, pathological review of 1716 patients with stage I
      to III curatively resected colorectal cancer who were treated at 11 institutions
      (1994-1998). In addition, 2242 patients from 9 institutions (1999-2003) were
      enrolled as a second cohort for validating results. EX were classified as
      isolated foci confined to vascular or perineural spaces (ie, lymphatic, venous,
      or perineural invasion) or as tumor nodules (ND). N- and T-staging systems
      employing different categories for staging were compared in terms of their
      prognostic power. In addition, the diagnoses of extramural, discontinuously
      spreading lesions made by 11 observers from different institutions were assessed
      for interobserver agreement. RESULTS: EX were observed in 18.2% of patients in
      the first cohort. The method of categorization of EX in tumor staging has a
      stronger impact on N than T staging. The N-staging system in which all ND types
      were classified as N factor (the ND rule) could more effectively stratify the
      survival outcome than the contour rule (Akaike information criterion, 3040.8 vs
      3059.5; the Harrell C-index, 0.7255 vs 0.7103). EX were observed in 16.9% of
      patients in the second cohort. Statistically, the ND rule was more informative
      than the contour rule for N staging. The Fleiss kappa coefficient for
      distinguishing LN metastases from EX (0.74) was lower than expected for complete
      agreement, and it decreased further to 0.51 when calculated for the judgment of
      ND with smooth contours. CONCLUSIONS: Classifying all ND types as N factors
      irrespective of contours can simplify the tumor staging system by enhancing
      diagnostic objectivity, resulting in improved prognostic accuracy.

PMID- 22395095
TI  - Voltage biasing, cyclic voltammetry, & electrical impedance spectroscopy for
      neural interfaces.
AB  - Electrical impedance spectroscopy (EIS) and cyclic voltammetry (CV) measure
      properties of the electrode-tissue interface without additional invasive
      procedures, and can be used to monitor electrode performance over the long term. 
      EIS measures electrical impedance at multiple frequencies, and increases in
      impedance indicate increased glial scar formation around the device, while cyclic
      voltammetry measures the charge carrying capacity of the electrode, and indicates
      how charge is transferred at different voltage levels.  As implanted electrodes
      age, EIS and CV data change, and electrode sites that previously recorded spiking
      neurons often exhibit significantly lower efficacy for neural recording.  The
      application of a brief voltage pulse to implanted electrode arrays, known as
      rejuvenation, can bring back spiking activity on otherwise silent electrode sites
      for a period of time.  Rejuvenation alters EIS and CV, and can be monitored by
      these complementary methods.  Typically, EIS is measured daily as an indication
      of the tissue response at the electrode site.  If spikes are absent in a channel
      that previously had spikes, then CV is used to determine the charge carrying
      capacity of the electrode site, and rejuvenation can be applied to improve the
      interface efficacy.   CV and EIS are then repeated to check the changes at the
      electrode-tissue interface, and neural recordings are collected.  The overall
      goal of rejuvenation is to extend the functional lifetime of implanted arrays.

PMID- 22395096
TI  - Surface state engineering of molecule-molecule interactions.
AB  - Engineering the electronic structure of organics through interface manipulation,
      particularly the interface dipole and the barriers to charge carrier injection,
      is of essential importance to improve organic devices. This requires the
      meticulous fabrication of desired organic structures by precisely controlling the
      interactions between molecules. The well-known principles of organic coordination
      chemistry cannot be applied without proper consideration of extra molecular
      hybridization, charge transfer and dipole formation at the interfaces. Here we
      identify the interplay between energy level alignment, charge transfer, surface
      dipole and charge pillow effect and show how these effects collectively determine
      the net force between adsorbed porphyrin 2H-TPP on Cu(111). We show that the
      forces between supported porphyrins can be altered by controlling the amount of
      charge transferred across the interface accurately through the relative alignment
      of molecular electronic levels with respect to the Shockley surface state of the
      metal substrate, and hence govern the self-assembly of the molecules.

PMID- 22395098
TI  - Oxide/water interfaces: how the surface chemistry modifies interfacial water
      properties.
AB  - The organization of water at the interface with silica and alumina oxides is
      analysed using density functional theory-based molecular dynamics simulation (DFT
      MD). The interfacial hydrogen bonding is investigated in detail and related to
      the chemistry of the oxide surfaces by computing the surface charge density and
      acidity. We find that water molecules hydrogen-bonded to the surface have
      different orientations depending on the strength of the hydrogen bonds and use
      this observation to explain the features in the surface vibrational spectra
      measured by sum frequency generation spectroscopy. In particular, 'ice-like' and
      'liquid-like' features in these spectra are interpreted as the result of hydrogen
      bonds of different strengths between surface silanols/aluminols and water.

PMID- 22395099
TI  - Cancer risk modelling and radiological protection.
AB  - Statistical models describing how the radiation-related risks of particular types
      of cancer vary with the doses of radiation received by specific tissues are
      derived from data gathered in epidemiological studies of exposed groups of
      people, guided by an incomplete understanding of radiobiological mechanisms
      gleaned from experimental studies. Cancer risk models have been developed for a
      dozen or so different types of cancer, and take account of the effect of
      important risk modifying factors such as age at exposure and time since exposure.
      Of primary importance in the development of cancer risk models is the experience
      of the Japanese atomic bomb survivors, but other exposed groups contribute
      information, including those exposed to radiation from internally deposited
      radioactive material, such as inhaled radon. Cancer risk models predict that at
      low doses or low dose rates the excess risk of cancer is directly proportional to
      the dose of radiation received, with no threshold dose--the linear no threshold
      (LNT) dose-response model--and the inferred summary estimate of the overall
      average lifetime excess risk of developing a serious cancer is ~ 5%/Sv. It is
      these cancer risk models and this inferred nominal risk estimate that provide the
      technical basis of radiological protection. Although it is difficult to
      definitively test the LNT model at low doses or low dose rates, because the
      predicted excess risk is small compared with fluctuations in the baseline risk,
      evidence exists that a small risk of cancer results from low-level exposure to
      radiation and that the excess risk is around that predicted by current risk
      models.

PMID- 22395100
TI  - Thermostable proteins in the diapausing eggs of Brachionus manjavacas (Rotifera).
AB  - Diapausing embryos (resting eggs) from brachionid rotifers are able to withstand
      desiccation and thermal stress. Resting eggs can remain viable for decades, and
      develop normally once placed in a permissive environment that allows for
      hatching, growth and development. The exact mechanisms of resistance are not
      known, although several molecules have been suggested to confer protection during
      desiccation and thermal stress. In this study, we have identified by mass
      spectrometry two thermostable proteins, LEA (late embryogenesis abundant) and VTG
      (vitellogenin-like), found exclusively in the resting eggs of Brachionus
      manjavacas. This is the first observation that LEA proteins may play a role in
      thermostability and the first report of a VTG-like protein in the phylum
      Rotifera. These proteins exhibited increased expression in rotifer resting eggs
      when compared to amictic females. Our data suggest the existence of alternate
      pathways of desiccation and thermal resistance in brachionid rotifers.

PMID- 22395101
TI  - Surface mobility regulates skeletal stem cell differentiation.
AB  - A family of polymer substrates which consists of a vinyl backbone chain with the
      side groups -COO(CH(2))(x)H, with x = 1, 2, 4, was prepared. Substrates with
      similar chemical groups but decreasing stiffness, characterized by their elastic
      modulus at 37  degrees C, as well as surface mobility, characterized by the glass
      transition temperature, were obtained. We have investigated whether these subtle
      variations in polymer chemistry lead to alterations in fibronectin (FN)
      adsorption and mesenchymal stem cell response. The same FN density was adsorbed
      on every substrate (~450 ng cm(-2)) although the supramolecular organization of
      the protein at the material interface, as obtained with AFM, was different for x
      = 1 and the other two surfaces (x = 2, 4). Consequently, this allows one to
      investigate the effect of physical properties of the matrix on stem cell
      differentiation after ruling out any influence of protein activity. Cell adhesion
      was quantified by calculating the size distribution of focal adhesions.
      Mesenchymal stem cell differentiation to the osteoblastic lineage was determined
      by quantifying protein levels for osteocalcin, osteopontin and Runx2, in the
      absence of any additional osteogenic soluble factors in the culture media, but as
      a direct effect of material properties. The findings indicate the potential to
      modulate skeletal progenitor cell commitment to the osteoblastic lineage through
      surface mobility of the underlying material surface.

PMID- 22395102
TI  - Managing alcohol withdrawal in hospitalized patients.

PMID- 22395097
TI  - Historical overview of immunological tolerance.
AB  - A fundamental property of the immune system is its ability to mediate self
      defense with a minimal amount of collateral damage to the host. The system uses
      several different mechanisms to achieve this goal, which is collectively referred
      to as the "process of immunological tolerance." This article provides an
      introductory historical overview to these various mechanisms, which are discussed
      in greater detail throughout this collection, and then briefly describes what
      happens when this process fails, a state referred to as "autoimmunity."

PMID- 22395103
TI  - Epidemiological investigations of aircrew: an occupational group with low-level
      cosmic radiation exposure.
AB  - Aircrew and passengers are exposed to low-level cosmic ionising radiation. Annual
      effective doses for flight crew have been estimated to be in the order of 2-5 mSv
      and can attain 75 mSv at career end. Epidemiological studies in this occupational
      group have been conducted over the last 15-20 years, usually with a focus on
      radiation-associated cancer. These studies are summarised in this note. Overall
      cancer risk was not elevated in most studies and subpopulations analysed, while
      malignant melanoma, other skin cancers and breast cancer in female aircrew have
      shown elevated incidence, with lesser risk elevations in terms of mortality. In
      some studies, including the large German cohort, brain cancer risk appears
      elevated. Cardiovascular mortality risks were generally very low. Dose
      information for pilots was usually derived from calculation procedures based on
      routine licence information, types of aircraft and routes/hours flown, but not on
      direct measurements. However, dose estimates have shown high validity when
      compared with measured values. No clear-cut dose-response patterns pointing to a
      higher risk for those with higher cumulative doses were found. Studies on other
      health outcomes have shown mixed results. Overall, aircrew are a highly selected
      group with many specific characteristics and exposures that might also influence
      cancers or other health outcomes. Radiation-associated health effects have not
      been clearly established in the studies available so far.

PMID- 22395104
TI  - [The PROSPECT study].

PMID- 22395105
TI  - [Almanac 2011: acute coronary syndromes. The national society journals present
      selected research that has driven recent advances in clinical cardiology].

PMID- 22395106
TI  - [The new ESC guidelines for non-ST-elevation acute coronary syndromes: one
      direction, many ways, clinical wisdom].
AB  - The 2011 edition of the ESC guidelines on non-ST-segment elevation acute coronary
      syndromes (NSTE-ACS) maintains the approach strongly based upon risk
      stratification, following the concept that "the higher the risk of ischemic
      events, the larger will be the benefit of an aggressive pharmaco-interventional
      approach". This concept applies both to the indication and timing of
      angiography/revascularization and to the choice of concomitant pharmacological
      therapies. The proofs of efficacy of the most recent drug treatments are solid,
      but the choice among the several available options and the evaluation of the
      efficacy/safety ratios in patient subsets require clinical wisdom, especially for
      the management of the most complex and frail patients. The indication for
      performing coronary angiography within 24h in high-risk patients would imply
      extending to NSTE-ACS patients the networks already in place for primary
      percutaneous coronary intervention in ST-elevation myocardial infarction.

PMID- 22395107
TI  - [Late stent thrombosis visualized with three-dimensional optical coherence
      tomography image reconstruction].

PMID- 22395109
TI  - More than a store: regulatory roles for glycogen in skeletal muscle adaptation to
      exercise.
AB  - The glycogen content of muscle determines not only our capacity for exercise but
      also the signaling events that occur in response to exercise. The result of the
      shift in signaling is that frequent training in a low-glycogen state results in
      improved fat oxidation during steady-state submaximal exercise. This review will
      discuss how the amount or localization of glycogen particles can directly or
      indirectly result in this differential response to training. The key direct
      effect discussed is carbohydrate binding, whereas the indirect effects include
      the metabolic shift toward fat oxidation, the increase in catecholamines, and
      osmotic stress. Although our understanding of the role of glycogen in response to
      training has expanded exponentially over the past 5 years, there are still many
      questions remaining as to how stored carbohydrate affects the muscular adaptation
      to exercise.

PMID- 22395108
TI  - [ESC guidelines for the management of acute coronary syndromes in patients
      presenting without persistent ST-segment elevation. The Task Force for the
      management of acute coronary syndromes (ACS) in patients presenting without
      persistent ST-segment elevation of the European Society of Cardiology (ESC)].

PMID- 22395110
TI  - Macrophage-specific transgenic expression of cholesteryl ester hydrolase
      attenuates hepatic lipid accumulation and also improves glucose tolerance in
      ob/ob mice.
AB  - Cellular cholesterol homeostasis is increasingly being recognized as an important
      determinant of the inflammatory status of macrophages, and a decrease in cellular
      cholesterol levels polarizes macrophages toward an anti-inflammatory or M2
      phenotype. Cholesteryl ester hydrolase (CEH) catalyzes the hydrolysis of stored
      intracellular cholesteryl esters (CE) and thereby enhances free cholesterol
      efflux and reduces cellular CE content. We have reported earlier reduced
      atherosclerosis as well as lesion necrosis and improved insulin sensitivity (due
      to decreased adipose tissue inflammation) in macrophage-specific CEH transgenic
      (CEHTg) mice in the LDLR(-/-) background. In the present study, we examined the
      effects of reduced intracellular accumulation of CE in CEHTg macrophages in an
      established diabetic mouse model, namely the leptin-deficient ob/ob mouse.
      Macrophage-specific transgenic expression of CEH improved glucose tolerance in
      ob/ob-CEHTg mice significantly compared with ob/ob nontransgenic littermates, but
      with no apparent change in macrophage infiltration into the adipose tissue.
      However, there was a significant decrease in hepatic lipid accumulation in ob/ob
      CEHTg mice. Consistently, decreased [(14)C]acetate incorporation into total
      lipids and triglycerides was noted in precision-cut liver slices from ob/ob-CEHTg
      mice. In the primary hepatocyte-macrophage coculture system, macrophages from
      CEHTg mice significantly reduced the incorporation of [(14)C]acetate into
      triglycerides in hepatocytes, indicating a direct effect of macrophages on
      hepatocyte triglyceride biosynthesis. Kupffer cells isolated from ob/ob-CEHTg
      mice were polarized toward an anti-inflammatory M2 (Ly6C(lo)) phenotype. Taken
      together, these studies demonstrate that transgenic overexpression of CEH in
      macrophages polarizes hepatic macrophages (Kupffer cells) to an anti-inflammatory
      M2 phenotype that attenuates hepatic lipid synthesis and accumulation.

PMID- 22395112
TI  - Lipopolysaccharide induces paired immunoglobulin-like receptor B (PirB)
      expression, synaptic alteration, and learning-memory deficit in rats.
AB  - Some typical immune proteins are expressed in the nervous system, among which the
      paired-immunoglobulin-like receptor B (PirB) is a receptor for major
      histocompatibility complex class I antigen (MHC-I), but may play a physiological
      role in the brain for neuronal circuitry stability by inhibiting synaptic
      plasticity. Chronic neuroinflammation is common to many neurodegenerative
      diseases and is often associated with neuronal/synaptic damage and dysfunction.
      Here we examined the expression of PirB in the rat brain following intracerebral
      application of lipopolysaccharide (LPS), which has been shown to induce
      proinflammatory changes and cognitive deficits in rodents. One month after
      unilateral intrahippocampal LPS injection (10 MUg in 4 MUl phosphate-buffered
      saline, PBS), increased protein levels and immunoreactivity of PirB were detected
      in the ipsilateral hippocampal formation and cortex of the experimental group
      relative to vehicle (PBS) control. The increased PirB labeling was localized to
      astrocytes and neurons. Reduced synaptophysin protein levels and immunoreactivity
      were also found in the ipsilateral hippocampal formation and cortex in LPS
      treated rats relative to controls. Morris water maze tests indicated that
      hippocampus-dependent spatial learning and memory were impaired in LPS-treated
      animals. Our findings add new experimental data for an upregulation of immune
      proteins in neuronal and glial cells in the brain in a model of endotoxin-induced
      neuroinflammation, synaptic alteration, and cognitive decline. The results
      suggest that PirB modulation may be involved in the pathological process under
      neurodegenerative conditions.

PMID- 22395111
TI  - Mitochondrial signaling contributes to disuse muscle atrophy.
AB  - It is well established that long durations of bed rest, limb immobilization, or
      reduced activity in respiratory muscles during mechanical ventilation results in
      skeletal muscle atrophy in humans and other animals. The idea that mitochondrial
      damage/dysfunction contributes to disuse muscle atrophy originated over 40 years
      ago. These early studies were largely descriptive and did not provide unequivocal
      evidence that mitochondria play a primary role in disuse muscle atrophy. However,
      recent experiments have provided direct evidence connecting mitochondrial
      dysfunction to muscle atrophy. Numerous studies have described changes in
      mitochondria shape, number, and function in skeletal muscles exposed to prolonged
      periods of inactivity. Furthermore, recent evidence indicates that increased
      mitochondrial ROS production plays a key signaling role in both immobilization
      induced limb muscle atrophy and diaphragmatic atrophy occurring during prolonged
      mechanical ventilation. Moreover, new evidence reveals that, during denervation
      induced muscle atrophy, increased mitochondrial fragmentation due to fission is a
      required signaling event that activates the AMPK-FoxO3 signaling axis, which
      induces the expression of atrophy genes, protein breakdown, and ultimately muscle
      atrophy. Collectively, these findings highlight the importance of future research
      to better understand the mitochondrial signaling mechanisms that contribute to
      disuse muscle atrophy and to develop novel therapeutic interventions for
      prevention of inactivity-induced skeletal muscle atrophy.

PMID- 22395113
TI  - Use of RotaFlow (MAQUET) for temporary right ventricular support during
      implantation of HeartMate II left ventricular assist device.
AB  - Temporary right ventricular (RV) support is considered during insertion of a left
      ventricular assist device in patients who are at risk of right ventricular
      dysfunction. There are several circuits and cannulation strategies available.
      Here, we report an effective and safe method for achieving RV support using the
      RotaFlow (Maquet) extracorporeal pump with inflow and outflow grafts placed
      through small opposing lateral thoracotomy incisions.

PMID- 22395114
TI  - Role of metalloproteinases and tissue inhibitors of metalloproteinases during
      cardiopulmonary bypass in rats.
AB  - Matrix metalloproteinases (MMPs) and the tissue inhibitors of matrix
      metalloproteinases (TIMPs) regulate matrix remodeling in the heart. Changes in
      synthesis and release of MMPs and TIMPs are observed after extracorporeal
      circulation (ECC). Thus, MMPs and TIMPs are supposed to be involved in ECC
      mediated cardiac dysfunction. The aim was to examine the role of MMPs and TIMPs
      in ECC-mediated cardiac dysfunction. Extracorporeal circulation was instituted in
      rats for 60 min at a flow rate of 120 ml/kg/min. Three groups (n = 10) were
      studied: group CAO: 60 min ECC without aortic cross-clamping, group CAC: 60 min
      ECC including 30 min aortic cross-clamping (crystalloid Inzolen((r))
      cardioplegia), and group CAB: 60 min ECC including 30 min aortic cross-clamping
      (blood cardioplegia). Left ventricular (LV) function was measured with
      conductance catheter. Matrix metalloproteinase-activity was determined by
      zymography and TIMP activity was determined by reverse zymography. Gene
      expression of MMPs and TIMPs was determined by real-time polymerase chain
      reaction. Sixty minutes after weaning from bypass, there was a preserved LV
      function in the CAO and CAB group and an impaired LV function in the CAC group.
      We observed an increased myocardial activity and an increased myocardial
      messenger RNA expression of MMP-2, MMP-9, TIMP-1, and TIMP-4 in all ECC groups,
      when compared with sham animals. With regard to enzyme activity, there was an
      imbalance of MMP/TIMP ratio leading to an increased activity of MMP in the CAC
      group. In terms of gene expression, there was an imbalance of MMP-2/TIMP-4 ratio
      leading to an increased expression of MMP-2 in the CAC group. MMP-2 contributes
      to myocardial reperfusion injury in this in vivo model of ECC with cardioplegic
      arrest.

PMID- 22395115
TI  - Evaluation of a new method for pulse push/pull hemodialysis: comparison with
      conventional hemodialysis.
AB  - The repetition of forward and backward filtration during hemodialysis (HD)
      increases convective mass transfer, and thus, the authors devised a method of
      achieving cyclic repletion of ultrafiltration and backfiltration. Hemodialytic
      efficiencies of the developed unit are described. The devised method, named pulse
      push/pull hemodialysis (PPPHD), is based on the utilization of dual pulsation in
      a dialysate stream. Clearances of solutes with different molecular weights were
      determined, and in vivo hemodialytic performance was investigated in a canine
      renal failure model. Urea and creatinine reduction and albumin (ALB) loss were
      monitored, and the results obtained were compared with those of a conventional
      high-flux hemodialysis (CHD). Dialysis sessions were repeated eight times for
      PPPHD and six times for CHD by alternating PPPHD and CHD sessions in a single
      animal, which remained stable throughout the experiments. Urea and creatinine
      reductions for the PPPHD unit were 49.2 +/- 2% and 44.3 +/- 3.3%, respectively,
      which were slightly higher than those obtained for the CHD. Total protein and ALB
      levels were preserved by both methods. However, in vitro results revealed that
      PPPHD achieved significantly greater inulin clearance than CHD. The developed
      PPPHD unit facilitates repetitive filtration and improves convective mass
      transfer during HD, without the need for external replacement infusion.

PMID- 22395116
TI  - Use of extracorporeal respiratory support during pregnancy: a case report and
      literature review.
AB  - We describe the case of a 25 year-old woman at 27 weeks of gestation who was
      admitted to our intensive care unit (ICU) for acute respiratory distress syndrome
      (ARDS) caused by pandemic 2009 H1N1 influenza A. She presented with septic shock
      and refractory hypoxemia unresponsive to rescue therapies such as recruitment
      maneuvers, prone positioning, and nitric oxide inhalation. Extracorporeal
      membrane oxygenation (ECMO) for respiratory support was instituted, and the
      patient's clinical conditions progressively improved: she was extubated after 16
      days and discharged from the ICU 3 days later. No fetal complications were
      observed. At 38 weeks of gestation she gave birth to a healthy baby.

PMID- 22395117
TI  - Derived and displayed power consumption, flow, and pulsatility over a range of
      HeartMate II left ventricular assist device settings.
AB  - Continuous-flow left ventricular assist devices/systems (LVADs/LVASs) reduce
      symptoms and mortality in severe heart failure. The impeller or centrifugal
      designs provide challenges in assessing and titrating pump speed (revolutions per
      minute [RPM]), flow, and native heart pulsatility, and contribution to cardiac
      output. The Thoratec HeartMate II (HM II) LVAS is the most commonly used LVAD
      worldwide. The user sets the RPM and the monitor provides online data on RPM,
      power consumption, flow, and pulsatility. These parameters are routinely used by
      clinicians to assess native heart function and to optimize pump settings.
      However, little is known about their reliability, reproducibility, and
      variability. Therefore, we assessed HM II controller parameters and concurrent
      echocardiography during titrations of RPM to low and high values. We found that
      data displayed on the monitor and logged in the controller are consistent for
      power consumption and for flow at settings above 8,000 RPM but inconsistent and
      unreliable for flow at or below 8,000 RPM and for pulsatility throughout a range
      of common settings and specifically at 9,000 RPM. These findings have
      implications for clinicians attempting to optimize settings and assess pump and
      native heart function.

PMID- 22395118
TI  - Lumped parameter model for heart failure with novel regulating mechanisms of
      peripheral resistance and vascular compliance.
AB  - To research the change in the physiological mechanism between the heart failure
      (HF) patient and healthy persons, the physiology parameters, which include the
      myocardial contractility, systemic vascular resistance (SVR), and vascular
      compliance, were studied. Through clinical data of HF patients, the computing
      method of the myocardial contractility was proposed; SVR as a function with
      respect to mean arterial pressure (MAP) was represented; and the vascular
      compliance was defined as a function with respect to MAP and cardiac output.
      Based on these parameters, a lumped parameter model of the cardiovascular system
      was established to reproduce the hemodynamic status of HF patients and verify the
      validity of the physiological mechanism. The simulation results demonstrate that
      the proportional error of mean flow, arterial pressure, and systolic blood
      pressure is 11.9%, 2.3%, and 4.7% compared with the clinical data, respectively.
      The proportional error of end-diastolic volume, end-systolic volume , and
      ejection fraction is 13.4%, 3%, and 3.9%, respectively.

PMID- 22395119
TI  - Thromboresistance characterization of extruded nitric oxide-releasing silicone
      catheters.
AB  - Intravascular catheters used in clinical practice can activate platelets, leading
      to thrombus formation and stagnation of blood flow. Nitric oxide (NO)-releasing
      polymers have been shown previously to reduce clot formation on a number of blood
      contacting devices. In this work, trilaminar NO-releasing silicone catheters were
      fabricated and tested for their thrombogenicity. All catheters had specifications
      of L = 6 cm, inner diameter = 21 gauge (0.0723 cm), outer diameter = 12 gauge
      (0.2052 cm), and NO-releasing layer thickness = 200 +/- 11 um. Control and NO
      releasing catheters were characterized in vitro for their NO flux and NO release
      duration by gas phase chemiluminescence measurements. The catheters were then
      implanted in the right and left internal jugular veins of (N = 6 and average
      weight = 3 kg) adult male rabbits for 4 hours thrombogenicity testing. Platelet
      counts and function, methemoglobin (metHb), hemoglobin (Hb), and white cell
      counts and functional time (defined as patency time of catheter) were monitored
      as measured outcomes. Nitric oxide-releasing catheters (N = 6) maintained an
      average flux above (2 +/- 0.5) * 10(-10) mol/min/cm for more than 24 hours,
      whereas controls showed no NO release. Methemoglobin, Hb, white cell, and
      platelet counts and platelet function at 4 hours were not significantly different
      from baseline (alpha = 0.05). However, clots on controls were visibly larger and
      prevented blood draws at a significantly (p < 0.05) earlier time (2.3 +/- 0.7
      hours) into the experiment, whereas all NO-releasing catheters survived the
      entire 4 hours test period. Results indicate that catheter NO flux levels
      attenuated thrombus formation in a short-term animal model.

PMID- 22395120
TI  - Clinical validation of a real-time data processing system for cardiac output and
      arterial pressure measurement during intraoperative biventricular pacing
      optimization.
AB  - Biventricular pacing (BiVP) improves cardiac output (CO) and mean arterial
      pressure (MAP) after cardiopulmonary bypass (CPB) in selected patients at risk
      for acute left heart failure after cardiac surgery. Optimization of
      atrioventricular delay (AVD) and interventricular delay (VVD) to maximize the
      hemodynamic effect of pacing requires rapid and accurate data processing.
      Conventional post hoc data processing (PP) is accurate but time-consuming, and
      infeasible in the intraoperative setting. We created a customized, real-time data
      processing (RTP) system to improve data processing efficiency, while maintaining
      accuracy. Biventricular pacing optimization was performed within 1 hour of the
      conclusion of CPB in 10 patients enrolled in the Biventricular Pacing After
      Cardiac Surgery trial. Cardiac output, measured by an electromagnetic flow meter,
      and arterial pressure were recorded as AVD was randomly varied across seven
      settings and VVD across nine settings. Post hoc data processing values calculated
      by two observers were compared to RTP-generated outputs for CO and MAP.
      Interexaminer reliability coefficients were generated to access the dependability
      of RTP. Interexaminer reliability coefficient values ranged from 0.997 to 0.999,
      indicating RTP is as reliable as PP for optimization. Real-time data processing
      is instantaneous and therefore is more practical in a clinical setting than the
      PP method. Real-time data processing is useful for guiding intraoperative BiVP
      optimization and merits further development.

PMID- 22395121
TI  - Combined use of Impella left ventricular assist device and extracorporeal
      membrane oxygenation as a bridge to recovery in fulminant myocarditis.
AB  - Myocarditis may result in cardiogenic shock, and when medical therapy is unable
      to maintain adequate cardiac output, mechanical circulatory support is indicated.
      This is the first reported case of a percutaneous left ventricular assist device
      being used in combination with extracorporeal membrane oxygenation in a patient
      with biventricular and respiratory failure, as a bridge to recovery.

PMID- 22395122
TI  - Impella and extracorporeal membrane oxygenation: a demanding combination.
AB  - We report the case of a 34-year-old woman admitted in our institution for
      cardiogenic shock related to acute myocarditis. Initial hemodynamic instability
      required mechanical ventilation and peripheral venoarterial extracorporeal
      membrane oxygenation (ECMO). Secondary acute pulmonary edema after ECMO
      implantation required emergency left ventricular decompression with a
      percutaneous Impella Recover LP 5.0. After a short period of improvement, an
      unexpected technical problem led to the Impella Recover LP 5.0 arrest. The
      clinical situation quickly worsened, and the patient finally died. This case
      highlights the usefulness of Impella pump to unload left cardiac chambers but
      also its technical challenge when used in a patient on ECMO.

PMID- 22395123
TI  - No donor age effect of human serum on collagen synthesis signaling and cell
      proliferation of human tendon fibroblasts.
AB  - The aging process of tendon tissue is associated with decreased collagen content
      and increased risk for injuries. An essential factor in tendon physiology is
      transforming growth factor-beta1 (TGF-beta1), which is presumed to be reduced
      systemically with advanced age. The aim of this study was to investigate whether
      human serum from elderly donors would have an inhibiting effect on the expression
      of collagen and collagen-related genes as well as on cell proliferative capacity
      in tendon cells from young individuals. There was no difference in systemic TGF
      beta1 levels in serum obtained from young and elderly donors, and we found no
      difference in collagen expression when cells were subjected to human serum from
      elderly versus young donors. In addition, tendon cell proliferation was similar
      when culture medium was supplemented with serum of different donor age. These
      findings suggest that factors such as the cell intrinsic capacity or the tissue
      specific environment rather than systemic circulating factors are important for
      functional capacity throughout life in human tendon cells.

PMID- 22395124
TI  - Medical effects and risks of exposure to ionising radiation.
AB  - Effects and risk from exposure to ionising radiation depend upon the absorbed
      dose, dose rate, quality of radiation, specifics of the tissue irradiated and
      other factors such as the age of the individual. Effects may be apparent almost
      immediately or may take decades to be manifest. Cancer is the most important
      stochastic effect at absorbed doses of less than 1 Gy. The risk of cancer
      induction varies widely across different tissues; however, the risk of fatal
      radiation-induced cancer for a general population following chronic exposure is
      about 5% Sv(-1). Quantification of cancer risk at doses of less than 0.1 Gy
      remains problematic. Hereditary risks from irradiation that might result in
      effects to offspring of humans appear to be much lower and any such potential
      risks can only be estimated from animal models. At high doses (over 1 Gy) cell
      killing and modification causes deterministic effects such as skin burns, and
      bone marrow depression, in which case immunosuppression becomes a critical issue.
      Acute whole body penetrating gamma irradiation at doses in excess of 2 Gy results
      in varying degrees of acute radiation sickness and doses over 10 Gy are usually
      lethal as a result of combined organ injury.

PMID- 22395125
TI  - Screening for adolescents' internalizing symptoms in primary care:  item response
      theory analysis of the behavior health screen depression, anxiety, and suicidal
      risk scales.
AB  - OBJECTIVE: To apply a modern psychometric approach to validate the Behavioral
      Health Screen (BHS) Depression, Anxiety, and Suicidal Risk Scales among
      adolescents in primary care. METHODS: Psychometric analyses were conducted using
      data collected from 426 adolescents aged 12 to 21 years (mean = 15.8, SD = 2.2).
      Rasch-Masters partial credit models were fit to the data to determine whether
      items supported the comprehensive measurement of internalizing symptoms with
      minimal gaps and redundancies. RESULTS: Scales were reduced to ensure that they
      measured singular dimensions of generalized anxiety, depressed affect, and
      suicidal risk both comprehensively and efficiently. Although gender bias was
      observed for some depression and anxiety items, differential item functioning did
      not impact overall subscale scores. Future revisions to the BHS should include
      additional items that assess low-level internalizing symptoms. CONCLUSIONS: The
      BHS is an accurate and efficient tool for identifying adolescents with
      internalizing symptoms in primary care settings. Access to psychometrically sound
      and cost-effective behavioral health screening tools is essential for meeting the
      increasing demands for adolescent behavioral health screening in
      primary/ambulatory care.

PMID- 22395126
TI  - Synthesis of fluorinated oxadiazoles with gelation and oxygen storage ability.
AB  - A new family of fluorinated low molecular weight (LMW) gelators has been
      synthesized through SNAr substitution of 5-polyfluoroaryl-3-perfluoroheptyl-1,2,4
      oxadiazoles with glycine ester. The obtained compounds give thermal and pH
      sensitive hydrogels or thermo-reversible organogels in DMSO. Oxygen solubility
      studies showed the ability to maintain high oxygen levels in solution and in gel
      blend with plate counter agar (PCA).

PMID- 22395127
TI  - Comparison of the distortion of probability information in decision under risk
      and an equivalent visual task.
AB  - Decision makers typically overweight small probabilities and underweight large
      probabilities. However, there are recent reports that when probability is
      presented in the form of relative frequencies, this typical pattern reverses. We
      tested this hypothesis by comparing decision making in two tasks: In one task,
      probability was stated numerically, and in the other task, it was conveyed
      through a visual representation. In the visual task, participants chose whether a
      "stochastic bullet" should be fired at either a large target for a small reward
      or a small target for a large reward. Participants' knowledge of probability in
      the visual task was the result of extensive practice firing bullets at targets.
      In the classical numerical task, participants chose between pairs of lotteries
      with probabilities and rewards matched to the probabilities and rewards in the
      visual task. We found that participants' probability-weighting functions were
      significantly different in the two tasks, but the pattern for the visual task was
      the typical, not the reversed, pattern.

PMID- 22395128
TI  - Is it light or dark? Recalling moral behavior changes perception of brightness.

PMID- 22395129
TI  - Fast thought speed induces risk taking.
AB  - In two experiments, we tested for a causal link between thought speed and risk
      taking. In Experiment 1, we manipulated thought speed by presenting neutral
      content text at either a fast or a slow pace and having participants read the
      text aloud. In Experiment 2, we manipulated thought speed by presenting fast-,
      medium-, or slow-paced movie clips that contained similar content. Participants
      who were induced to think more quickly took more risks with actual money in
      Experiment 1 and reported greater intentions to engage in real-world risky
      behaviors, such as unprotected sex and illegal drug use, in Experiment 2. These
      experiments provide evidence that faster thinking induces greater risk taking.

PMID- 22395130
TI  - Get me out of this slump! Visual illusions improve sports performance.

PMID- 22395131
TI  - The perception of a face is no more than the sum of its parts.
AB  - When you see a person's face, how do you go about combining his or her facial
      features to make a decision about who that person is? Most current theories of
      face perception assert that the ability to recognize a human face is not simply
      the result of an independent analysis of individual features, but instead
      involves a holistic coding of the relationships among features. This coding is
      thought to enhance people's ability to recognize a face beyond what would be
      expected if each feature were shown in isolation. In the study reported here, we
      explicitly tested this idea by comparing human performance on facial-feature
      integration with that of an optimal Bayesian integrator. Contrary to the
      predictions of most current notions of face perception, our findings showed that
      human observers integrate facial features in a manner that is no better than
      would be predicted by their ability to use each individual feature when shown in
      isolation. That is, a face is perceived no better than the sum of its individual
      parts.

PMID- 22395132
TI  - Visual rivalry without spatial conflict.
AB  - Visual rivalry has been extensively characterized in the literature. It is
      thought to require spatial conflict between overlapping visual presentations,
      even in studies that have found nonspatial (i.e., nonretinal) influences on
      rivalry. Unexpectedly, we identified visual rivalry in the complete absence of
      spatial conflict. Participants experienced visual rivalry when we placed a
      nonambiguous motion stimulus in a nonspatial (in our case, object-based)
      reference frame. Moreover, a stimulus that was displaced within a nonspatial
      reference frame did not induce rivalry despite the presence of spatial conflict.
      This finding shows that nonspatial, object-based processing can overrule
      retinotopic processing and prevent rivalry from occurring when a perceived
      stimulus exists unambiguously in an object-based reference frame. Our results
      identify a potent high-level conflict-resolution stage independent of low-level
      spatial visual conflict. This independence of spatial overlap provides an
      advantage to the visual system, allowing conflict resolution when an object is
      nonstationary on the retina (e.g., during frequently occurring eye movements).

PMID- 22395133
TI  - Effects of symptom presentation order on perceived disease risk.
AB  - People are quick to perceive meaningful patterns in the co-occurrence of events.
      We report two studies exploring the effects of streaks in symptom checklists on
      perceived personal disease risk. In the context of these studies, a streak is a
      sequence of consecutive items on a list that share the characteristic of being
      either general or specific. We identify a psychological mechanism underlying the
      effect of streaks in a list of symptoms and show that the effect of streaks on
      perceived risk varies with the length of the symptom list. Our findings reveal a
      tendency to infer meaning from streaks in medical and health decision making.
      Participants perceived a higher personal risk of having an illness when presented
      with a checklist in which common symptoms were grouped together than when
      presented with a checklist in which these same symptoms were separated by rare
      symptoms. This research demonstrates that something as arbitrary as the order in
      which symptoms are presented in a checklist can affect perceived risk of disease.

PMID- 22395134
TI  - Health risks associated with environmental radiation exposures.
AB  - Much is known about health effects associated with exposure to ionising
      radiation. Numerous epidemiologic studies of populations exposed to radiation
      under a variety of circumstances have been conducted. These studies have clearly
      shown that radiation exposure can result in an increased risk of many types of
      cancer, and the findings are supported by a substantial body of literature from
      experimental studies. Despite the fact that radiation exposures from
      environmental sources comprise a relatively minor component of total population
      exposure, this type of exposure is often the most feared by the public. An
      accident like Chernobyl or a natural disaster like that at Fukushima provides a
      unique opportunity to learn more about the health risks from environmental
      radiation exposures. However, establishing the infrastructure and expertise
      required to design and conduct all aspects of a complex field study presents
      formidable challenges. This paper summarises the principal findings from the main
      studies of environmental radiation exposure that have been successfully
      undertaken. Although such studies are often exceedingly difficult to conduct, and
      may be limited by an ecologic design, they can be informative in assessing risk.
      Any new environmental study that is initiated should focus on special
      circumstances; additional ecological studies are not recommended.

PMID- 22395135
TI  - Trans-differentiation of the adipose tissue-derived stem cells into neuron-like
      cells expressing neurotrophins by selegiline.
AB  - BACKGROUND: Adult stem cells (ASC) are undifferentiated cells found throughout
      the body. These cells are promising tools for cell replacement therapy in
      neurodegenerative disease. Adipose tissue is the most abundant and accessible
      source of ASC. This study was conducted to evaluate effect of selegiline on
      differentiation of adipose-derived stem cells (ADSC) into functional neuron-like
      cells (NLC), and also level of the neurotrophin expression in differentiated
      cells. METHODS: ADSC were transdifferentiated into NLC using selegiline where
      CD90, CD49d, CD31, CD106 and CD45 were used as markers for ADSC identification.
      Lipogenic and osteogenic differentiation of ADSC were used to characterize the
      ADSC. ADSC were treated with selegiline at different concentrations (from 10(-6)
      to 10(-11) mM) and time points (3, 6, 12, 24 and 48 h). Percentage of viable
      cells, nestin and neurofilament 68 (NF-68) immunoreactive cells were used as
      markers for differentiation. The optimal dose for neurotrophin expressions in
      differentiating cells was evaluated using reverse transcriptase-PCR. NLC function
      was evaluated by loading and unloading with FM1-43 dye. RESULTS: ADSC were
      immunoreactive to CD90 (95.67 +/- 2.26), CD49d (71.52 +/- 6.64) and CD31 (0.6 +/-
      0.86), but no immunoreactivity was detected for CD106 and CD45. The results of
      neural differentiation showed the highest percentage of nestin and NF-68 positive
      cells at 10(-9) mM concentration of selegiline (exposed for 24 h). The
      differentiated cells expressed synapsin and neurotrophin genes except brain
      derived neurotrophic factor. CONCLUSION: ADSC can be an alternative source in
      cell-based therapy for neurodegenerative diseases using selegiline to induce ADSC
      differentiation to neuronal lineage.

PMID- 22395136
TI  - Impact of DNA damage on the frequency of sperm chromosomal aneuploidy in normal
      and subfertile men.
AB  - BACKGROUND: Various frequencies of sperm aneuploidy are reported in sperms of
      subfertile patients compared to normal individuals. Moreover, sperm DNA damage is
      shown to be associated with male infertility. In this study, the rate of DNA
      damage and frequencies of aneuploidy in sperms of subfertile patients was
      investigated. METHODS: Semen samples were obtained from healthy normal and
      subfertile (oligozoospermia, asthenozoospermia, and oligoasthenozoospermia) men.
      The frequency of aneuploidy was assessed using primed in situ labeling (PRINS)
      analysis with specific primers for chromosomes 18, 21, X, and Y. Sperm DNA damage
      was assessed using alkaline comet assay. RESULTS: The mean frequencies of disomy
      for the patients were significantly higher than normal for all chromosomes (P <
      0.01). The extent of DNA damage in sperms of subfertiles was significantly higher
      than in normal individuals (P < 0.001). The obtained results indicated that
      higher rate of DNA damages led to higher frequency of chromosomal disomy except
      for asthenozoospermia samples which exhibited higher rate of DNA damage and lower
      frequency of chromosomal disomy. CONCLUSIONS: These results demonstrate that men
      with oligozoospermia and oligoasthenozoospermia have an elevated risk for
      chromosome abnormalities in their sperm, particularly sex chromosomes. DNA damage
      might be involved in the process of malsegregation of chromosomes.

PMID- 22395137
TI  - Induction of apoptosis and non-apoptosis in human breast cancer cell line (MCF-7)
      by cisplatin and caffeine.
AB  - BACKGROUND: Molecular targeted therapy by different cell death inducers are
      recently considered in cancer therapy. The aim of this study was to compare the
      effect of cisplatin and inositol trisphosphate kinase inhibitor (caffeine) on
      human breast cancer cell line (MCF-7). The pattern of cell death in MCF-7 cells
      following the exposure to cisplatin and caffeine in individual and combination
      forms was characterized. METHODS: MCF-7 cells at late exponential phase were
      divided into two groups: control and experimental groups. Experimental group was
      exposed to cisplatin, caffeine and combination of them and control group was
      treated by vehicle. Forty-eight hours after incubation, floating and attached
      cells were collected separately. Flow cytometry analysis and electron microscopy
      were carried out on both attached and floating cells. RESULTS: Two types of
      apoptotic and non-apoptotic cells were observed in the floating cells as well as
      in sub G1 cells of both experimental and control groups by electron microscopy.
      Both early and late stages of apoptosis were characterized and the attached cells
      remained unaffected. CONCLUSION: Although two different forms of cell death
      (apoptosis and non-apoptosis) were appeared in MCF-7 following exposure to
      cisplatin and caffeine, apoptosis was the major mechanism of cell death. The
      combination form of anti-cancer drugs with different mechanisms could decrease
      the dosage of employed anti-cancer drugs.

PMID- 22395139
TI  - Combination effects of prednisolone and interleukin-4 protect bovine nasal
      cartilage explants from interleukin-1alpha induced degradation.
AB  - BACKGROUND: Current treatments for joint diseases are moderately successful, but
      unfortunately are associated with significant side effects. This study was
      undertaken to investigate the combination effects of IL-4 and prednisolone on
      tissue characteristics and production of matrix metalloproteinase-1(MMP-1) in IL
      lalpha-treated bovine nasal cartilage (BNC) explants. METHODS: BNC explants were
      cultured in DMEM with IL-lalpha (10 ng/ml), IL-4 (50 ng/ml) and prednisolone (1
      or 1,000 nM) at the same time for 28 days. At days 3, 7, 14, 21 and 28, the media
      were collected and replaced with fresh media, and the removed media were stored
      at -20 degrees C. The alterations of tissue characteristics were assessed by
      using histology techniques. Western-blot method was used to determine the effects
      of IL-4 and prednisolone combination on MMP-1 production. The cell viability was
      evaluated by using lactate dehydrogenase assay test. RESULTS: In the presence of
      IL-lalpha alone, most chondrocytes were transformed into fibroblast-like
      morphology with pyknotic nuclei at day 28. In addition, a clear band of MMP-1 and
      extracellular matrix (ECM) degradation were observed. In combination of IL-4 and
      prednisolone, chondrocytes preserved their ordinary normal features. MMP-1 band
      formation was completely inhibited and ECM absolutely showed normal
      characteristics. IL-4 and prednisolone did not show cytotoxicity effects on BNC
      explant culture. CONCLUSION: This combination can strongly preserve cartilage
      from degradation features and the data possibly suggest that the combination of
      IL-4 and prednisolone could be a candidate for alternative therapy in joint
      diseases.

PMID- 22395138
TI  - Antioxidant and free radical scavenging potential of yakuchinone B derivatives in
      reduction of lipofuscin formation using H2O2-treated neuroblastoma cells.
AB  - BACKGROUND: The progressive accumulation of misfolded and aggregated proteins in
      neurons is an accepted mechanism in aging. Overproduction of reactive oxygen
      species (ROS), referred to as oxidative stress, is currently believed to play a
      pivotal role in this process. Lipofuscin as a histological index of aging results
      from cross-links between oxidized proteins and lipids. Therefore, to attenuate
      lipofuscin formation, it would be logical to use exogenous natural or synthetic
      antioxidants. Yakuchinone B (1-[4'-hydroxy-3'-methoxyphenyl]-7-phenylhept-1-en-3
      one) is a component of Alpinia oxyphylla seeds with established antioxidant
      activity. METHODS: To evaluate the neuroprotective roles of yakuchinone B (JC6)
      and its structural analogues (JC1-JC5), the free radical scavenging capabilities
      of yakuchinone B derivatives were studied in terms of cell viability, apoptosis,
      cells ROS content, catalase (CAT) and superoxide dismutase (SOD) activity and the
      intracellular lipofuscin content in SK-N-MC cells exposed to H2O2. The level of
      MDA (malondialdehyde), as an index of lipid peroxidation and acid phosphatase
      activity were also measured. RESULTS: Our results indicated that derivatives
      especially JC4, JC5 and JC6 decreased the extent of apoptosis and ROS level,
      while they increased the activities of SOD and CAT in drug-pretreated cells as
      compared to H2O2-treated cells. A clear relationship between the structure and
      antioxidant activities of these compounds was established. In addition, JC4, JC5
      and JC6 were capable of down-regulating the formation of MDA and lipofuscin.
      CONCLUSION: Our results indicated that free radicals play significant roles in
      lipofuscin formation and cellular aging which can be attenuated by yakuchinone B
      derivatives.

PMID- 22395140
TI  - Down-regulation of metallothionein 1 and 2 after exposure to electromagnetic
      field in mouse testis.
AB  - BACKGROUND: It is proved that testis is sensitive to electromagnetic field (EMF)
      and its damage results in infertility. Exposure to EMF induces reactive oxygen
      species production and affects on anti-oxidants defense mechanisms.
      Metallothionein (MT) is a name for a group of low molecular weight (6-7 kDa),
      sulfhydryl rich proteins. Expression of MT1 and MT2 genes in testis tissue after
      EMF exposure was aimed in this study. METHODS: Male BALB/c mice (8 weeks old)
      were exposed to 3 MT EMF for 8 weeks, 4 hours/day. After 8 weeks, the mice were
      sacrificed and the testis tissue was removed. The testis pieces were stained with
      hematoxylin and eosin and analyzed under an optical microscope. Assessment of MT1
      and MT2 genes and also protein expression was performed by real-time PCR and
      Western-blot, respectively. RESULTS: In light microscopic observation, the number
      of primary spermatocytes was increased significantly in EMF group (P < 0.01). In
      addition, in interstitial space, the number of leydig cells was increased
      significantly in EMF group (P < 0.01) and basement membrane thickness was
      increased as well. MT1 and MT2 genes were down-regulated significantly in testis
      tissue of mice exposed to EMF both in mRNA and protein level compared to control.
      CONCLUSION: It is clear that MT is mediated in testis development and
      spermatogenesis. Down-regulation of MT1 and MT2 after EMF in mouse testis might
      be followed by some consequences that result in infertility.

PMID- 22395142
TI  - Effect of oleuropein on tissue myeloperoxidase activity in experimental spinal
      cord trauma.
AB  - BACKGROUND: Neutrophil infiltration plays an important role in inflammatory
      reactions following spinal cord injury (SCI) and these cells cause substantial
      secondary tissue damage. The purpose of this study was to determine the effect of
      oleuropein (OE) on myeloperoxidase (MPO) activity as an index of neutrophil
      infiltration. METHODS: Rats were randomly divided into four groups of 7 rats each
      as follows: sham-operated group, trauma group, and OE treatment groups (20 mg/kg,
      i.p., immediately and 1 hour after SCI). Spinal cord samples were taken 24 hours
      after injury and studied for determination of MPO activity. RESULTS: The results
      showed that MPO activity was significantly decreased in OE-treated rats.
      CONCLUSION: On the basis of our findings, we propose that OE may be effective in
      protecting rat spinal cord from secondary damage by modulating of neutrophil
      infiltration.

PMID- 22395141
TI  - Morphometrical study of polysialylated neural cell adhesion molecule positive
      cells in rat pups hippocampus following induction of seizure during pregnancy.
AB  - BACKGROUND: The polysialylated neural cell adhesion molecule (PSA-NCAM) is
      expressed in developing brain. Fetal brain damage is caused by different
      conditions such as seizure and hypoxia. The present study was designed to
      investigate the effect of maternal seizures on the number of PSA-NCAM positive
      cells in pup's hippocampus. METHODS: Female Wistar rats were divided into four
      groups: (a) kindled rats which received PTZ (40 mg/kg, i.p.) during pregnancy
      from embryonic day 14-19 (E14-E19) every 48 h, (b) kindled rats which did not
      receive PTZ during pregnancy, (c) non-kindle, pregnant rats which received PTZ
      injection (40 mg/kg, i.p.) during pregnancy from E14 to E19 every 48 h, and (d)
      non-kindle, pregnant rats which received injection with an equal volume of normal
      saline as sham controls. At postnatal day 14 (PD14), rat pups were perfused, and
      their brain were fixed, embedded and coronal sections stained by
      immunohistochemistry method. The number of PSA-NCAM positive cells per unit area
      in the pup's hippocampus was counted. RESULTS: The number of PSA-NCAM positive
      cells in the CA1, CA3, and DG fields of pup's hippocampus, which was obtained
      from mothers who experienced PTZ injection during pregnancy, was decreased
      approximately 2.6 (P = 0.001), 2 (P = 0.001), and 2.1 (P = 0.001) times compared
      with non-PTZ treated maternal groups, respectively. CONCLUSIONS: Our study showed
      that maternal seizures reduced the number of neurons and also PSA-NCAM positive
      cells per unit area in the offspring hippocampus that it may cause impairment in
      hippocampal functions.

PMID- 22395143
TI  - Vibrational spectrum at a water surface: a hybrid quantum mechanics/molecular
      mechanics molecular dynamics approach.
AB  - A hybrid quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD)
      simulation is applied to the calculation of surface orientational structure and
      vibrational spectrum (second-order nonlinear susceptibility) at the vapor/water
      interface for the first time. The surface orientational structure of the QM water
      molecules is consistent with the previous MD studies, and the calculated
      susceptibility reproduces the experimentally reported one, supporting the
      previous results using the classical force field MD simulation. The present QM/MM
      MD simulation also demonstrates that the positive sign of the imaginary part of
      the second-order nonlinear susceptibility at the lower hydrogen bonding OH
      frequency region originates not from individual molecular orientational
      structure, but from cooperative electronic structure through the hydrogen bonding
      network.

PMID- 22395144
TI  - Utility of the bladder flap at cesarean delivery: a randomized controlled trial.
AB  - OBJECTIVE: To test the hypothesis that omission of the bladder flap in primary
      and repeat cesarean deliveries shortens operating time without increasing
      intraoperative and postoperative complications. METHODS: We randomized 258 women
      undergoing primary and repeat cesarean deliveries at 32 weeks of gestation or
      more to creation (n=131) or omission (n=127) of the bladder flap. Emergency
      cesarean deliveries, planned vertical uterine incisions, and previous abdominal
      surgeries besides cesarean deliveries were excluded. The primary outcome measure
      was total operating time. Secondary outcomes were bladder injury, incision-to
      delivery time, incision-to-fascial closure time, estimated blood loss,
      postoperative microhematuria, postoperative pain, hospital days, endometritis,
      and urinary tract infection. Analysis followed the intention-to-treat principle.
      RESULTS: The median skin incision to delivery interval was shorter with omission
      of the bladder flap (9 [range 1-43] compared with 10 [range 2-70] minutes;
      P=.04), but there was no difference in total operating time (51 [range 18-124]
      minutes compared with 51 [range 16-178]; P=.10). No bladder injuries occurred in
      either group and there were no significant differences in estimated blood loss,
      change in hemoglobin level, postoperative microhematuria, postoperative pain,
      hospital days, endometritis, or urinary tract infection. CONCLUSION: Omission of
      the bladder flap at primary and repeat cesarean deliveries does not increase
      intraoperative or postoperative complications. Incision-to-delivery time is
      shortened but total operating time appears unchanged. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov,www.ClinicalTrials.gov, NCT00918996. LEVEL OF
      EVIDENCE: I.

PMID- 22395145
TI  - Predictors of successful surgical outcome in laparoscopic hysterectomy.
AB  - OBJECTIVE: To estimate, after correction for patient factors, to what extent
      blood loss, operative time, and adverse events are decisive factors for the
      successful outcome of laparoscopic hysterectomy. A secondary objective was to
      estimate to what extent a successful outcome can be predicted from surgical
      experience or other measures of surgical skill. METHODS: A nationwide
      multivariate 1-year cohort analysis was conducted with gynecologists who perform
      laparoscopic hysterectomy. The primary outcomes were blood loss, operative time,
      and adverse events. The procedures were corrected for multiple covariates in a
      mixed-effects logistic regression model. Furthermore, all primary outcomes were
      related to experience and the influence of individual surgical skills factors.
      RESULTS: One thousand five hundred thirty-four laparoscopic hysterectomies were
      analyzed for 79 surgeons. The success of the surgical outcome was significantly
      influenced by uterus weight, body mass index, American Society of
      Anesthesiologists Physical Status Classification, previous abdominal surgeries,
      and the type of laparoscopic hysterectomy. Surgical experience also predicted the
      successful outcome of laparoscopic hysterectomy with respect to blood loss and
      adverse events (P=.048 and .036, respectively). A significant improvement in
      surgical outcomes tends to continue up to approximately 125 procedures.
      Independently from surgical experience, an individual surgical skills factor was
      identified as odds ratio 1.67 and 3.60 for blood loss and operative time,
      respectively. CONCLUSION: After adjusting for risk factors, it was shown that an
      increase in experience positively predicted a successful outcome in laparoscopic
      hysterectomy with respect to blood loss and adverse events. However, the
      independent surgical skills factor shows a large variation in proficiency between
      individuals. The fact that a surgeon has performed many laparoscopic
      hysterectomies does not necessarily guarantee good surgical outcome. LEVEL OF
      EVIDENCE: II.

PMID- 22395146
TI  - An over-the-counter simulation study of a single-tablet emergency contraceptive
      in young females.
AB  - OBJECTIVES: To evaluate use of a single-tablet (levonorgestrel 1.5 mg) emergency
      contraceptive administered to young females under simulated over-the-counter
      conditions. Secondary objectives were to assess repeat use, pregnancy, and
      adverse events. METHODS: Females aged 11-17 years requesting emergency
      contraception at teen reproductive health clinics in five cities were eligible to
      participate. Participants read the study product label and determined whether and
      how to use the product without interacting with providers. Study product was
      dispensed to participants who appropriately selected to use it; participants were
      contacted 1, 4, and 8 weeks later to assess use, pregnancy, and adverse events.
      The incidences of outcomes were calculated and regression analysis was used to
      assess the effect of age and use status (ever used or no previous use) on primary
      outcomes. RESULTS: Of the 345 females enrolled, 279 were younger than age 17
      years. Among the 340 participants included in the selection analysis, 311 (91.5%)
      (97.5% confidence interval 87.5- 94.5%) participants appropriately selected to
      use or not use product. Among the 298 participants who used product, 274 (92.9%)
      (97.5% confidence interval 88.8-95.8%) correctly used it as labeled. Selection
      and correct use were not associated with age. Fifty-seven participants (18.8%)
      used additional emergency contraception over the study period and seven (2.3%)
      participants who used product became pregnant; there were no unusual adverse
      events. CONCLUSION: Restricting young females' use of a single-tablet emergency
      contraceptive by prescription only is not warranted, because females younger than
      17 years can use it in a manner consistent with over-the-counter access. LEVEL OF
      EVIDENCE: II.

PMID- 22395147
TI  - Evanescent photosynthesis: exciting cyanobacteria in a surface-confined light
      field.
AB  - The conversion of solar energy to chemical energy useful for maintaining cellular
      function in photosynthetic algae and cyanobacteria relies critically on light
      delivery to the microorganisms. Conventional direct irradiation of a bulk
      suspension leads to non-uniform light distribution within a strongly absorbing
      culture, and related inefficiencies. The study of small colonies of cells in
      controlled microenvironments would benefit from control over wavelength,
      intensity, and location of light energy on the scale of the microorganism. Here
      we demonstrate that the evanescent light field, confined near the surface of a
      waveguide, can be used to direct light into cyanobacteria and successfully drive
      photosynthesis. The method is enabled by the synergy between the penetration
      depth of the evanescent field and the size of the photosynthetic bacterium, both
      on the order of micrometres. Wild type Synechococcus elongatus (ATCC 33912) cells
      are exposed to evanescent light generated through total internal reflection of
      red (lambda = 633 nm) light on a prism surface. Growth onset is consistently
      observed at intensity levels of 79 +/- 10 W m(-2), as measured 1 MUm from the
      surface, and 60 +/- 8 W m(-2) as measured by a 5 MUm depthwise average. These
      threshold values agree well with control experiments and literature values based
      on direct irradiation with daylight. In contrast, negligible growth is observed
      with evanescent light penetration depths less than the minor dimension of the rod
      like bacterium (achieved at larger light incident angles). Collectively these
      results indicate that evanescent light waves can be used to tailor and direct
      light into cyanobacteria, driving photosynthesis.

PMID- 22395148
TI  - The chemopreventive agent ursodeoxycholic acid inhibits proliferation of colon
      carcinoma cells by suppressing c-Myc expression.
AB  - Ursodeoxycholic acid (UDCA) can prevent chemical and colitis-associated colon
      carcinogenesis by unknown mechanism(s). One of the processes underlying the
      chemopreventive action could be the inhibition of proliferation by UDCA. To
      clarify the antiproliferative mechanism of UDCA, we used p53 wt colon carcinoma
      cell lines HCT8 and HCT116. UDCA-induced inhibition of proliferation was
      reversible and was associated with a decrease of the S-phase and an increase of
      G1 phase population, but not with apoptosis or senescence. The treatment
      suppressed the expression of c-Myc protein and, as a consequence, of several cell
      cycle regulatory molecules, including CDK4 and CDK6. Using the HCT8 cell line as
      a model, we show that UDCA suppresses c-Myc at the protein level. The suppression
      of c-Myc alone or a simultaneous suppression of CDK4 and of CDK6 kinase is
      sufficient to inhibit cell proliferation. In sum, we identified c-Myc as a
      primary UDCA target in colon carcinoma cells. The degradation of c-Myc protein
      decreases the expression of the cell cycle regulators CDK4 and CDK6, which
      reversibly slows down the cell cycle. The suppression of these proproliferatory
      molecules is the likely initial mechanism of antiproliferatory action of UDCA on
      colon cancer cells.

PMID- 22395149
TI  - Recent progress in biological charge transfer: theory and simulation.
AB  - In this contribution, we discuss three recent developments in atomistic
      biological charge transfer theory. First, in the context of Marcus' classical
      theory of charge transfer, key quantities of the theory such as driving forces
      and reorganization enthalpies are now accessible by thermodynamic integration
      schemes within standard molecular dynamics simulations at high accuracy. Second,
      direct simulations of charge transfer enable the computation of fast charge
      transfer reaction rates without having to resort to Marcus' theory. Finally,
      exploring the electronic structure beyond that of hitherto presumed centers of
      localization helps to identify new stepping stones of charge transfer reactions.
      This article is part of a Special Issue entitled: 17th European Bioenergetics
      Conference (EBEC 2012).

PMID- 22395150
TI  - Extinction coefficient for red-shifted chlorophylls: chlorophyll d and
      chlorophyll f.
AB  - Both chlorophyll f and chlorophyll d are red-shifted chlorophylls in oxygenic
      photosynthetic organisms, which extend photon absorbance into the near infrared
      region. This expands the range of light that can be used to drive photosynthesis.
      Quantitative determination of chlorophylls is a crucial step in the investigation
      of chlorophyll-photosynthetic reactions in the field of photobiology and
      photochemistry. No methods have yet been worked out for the quantitative
      determination of chlorophyll f. There is also no method available for the precise
      quantitative determination of chlorophyll d although it was discovered in 1943.
      In order to obtain the extinction coefficients (epsilon) of chlorophyll f and
      chlorophyll d, the concentrations of chlorophylls were determined by Inductive
      Coupled Plasma Mass Spectrometry according to the fact that each chlorophyll
      molecule contains one magnesium (Mg) atom. Molar extinction coefficient
      epsilon(chl f) is 71.11*10(3)Lmol(-1)A(707nm)cm(-1) and epsilon(chl d) is
      63.68*10(3)Lmol(-1)A(697nm)cm(-1) in 100% methanol. This article is part of a
      Special Issue entitled: Photosynthesis Research for Sustainability: from Natural
      to Artificial.

PMID- 22395151
TI  - N-Heterocyclic carbene chemistry of iron: fundamentals and applications.
AB  - The use of N-heterocyclic carbenes (NHCs) in the chemistry of iron is stimulating
      important new applications of one of the most ubiquitous ligand types in modern
      organometallic chemistry. A series of reports has shown how the flexible and
      modifiable stereo-electronic properties of NHC ligands can be combined with iron
      in a range of oxidation states to create opportunities for studying unique
      structures, bonding and reactivity. Of particular interest are the roles of iron
      NHC complexes in: the stabilization of unusual oxidation states and coordination
      environments; the activation of small molecules; homogeneous catalysis; and bio
      mimetic chemistry. Our feature article summarizes the key developments in the
      field.

PMID- 22395152
TI  - Cargo-towing synthetic nanomachines: towards active transport in microchip
      devices.
AB  - This review article discusses the use of synthetic catalytic nano motors for
      cargo manipulations and for developing miniaturized lab-on-chip systems based on
      autonomous transport. The ability of using chemically-powered artificial
      nanomotors to capture, transport and release therapeutic payloads or
      nanostructured biomaterials represents one of the next major prospects for
      nanomotor development. The increased cargo-towing force of such self-propelled
      nanomotors, along with their precise motion control within microchannel networks,
      versatility and facile functionalization, pave the way to new integrated
      functional lab-on-a-chip powered by active transport and perform a series of
      tasks. Such use of cargo-towing artificial nanomotors has been inspired by on
      chip kinesin molecular shuttles. Functionalized nano/microscale motors can thus
      be used to pick a selected nano/microscale chemical or biological payload target
      at the right place, transport and deliver them to a target location in a timely
      manner. Key challenges for using synthetic nanomachines for driving transport
      processes along microchannel networks are discussed, including loading and
      unloading of cargo and precise motion control, along with recent examples of
      related cargo manipulation processes and guided transport in lab-on-a-chip
      formats. The exciting research area of cargo-carrying catalytic man-made
      nanomachines is expected to grow rapidly, to lead to new lab-on-a-chip formats
      and to provide a wide range of future microchip opportunities.

PMID- 22395153
TI  - Correlation between homeodomain-interacting protein kinase 2 and apoptosis in
      cervical cancer.
AB  - Homeodomain-interacting protein kinase 2 (HIPK2) is a serine/threonine nuclear
      kinase that is involved in apoptosis and cell growth, and is also thought to play
      a role in the process of tumorigenesis. The purpose of this study was to identify
      the role of HIPK2 in cervical cancer. HIPK2 expression was examined in normal and
      cervical cancer tissues at the mRNA and protein levels by quantitative real-time
      PCR and western blotting. To investigate the mechanism of action of HIPK2 in
      cervical cancer, RNA interference was used to analyze the effect of HIPK2 on
      apoptosis and cell growth in cervical cell lines. The results showed that HIPK2
      expression was significantly higher in the cervical cancer tissues compared to
      the normal cervical tissues, both at the mRNA and protein level. Moreover,
      inhibition of HIPK2 promoted cell growth and decreased the rate of cell apoptosis
      in cervical cell lines. Taken together, these results indicate that HIPK2
      expression is higher in cervical cancer tissues and has a positive correlation
      with cervical cancer. HIPK2 may be important in the development of cervical
      cancer.

PMID- 22395154
TI  - Protection of people living in long-term contaminated areas after a nuclear
      accident: the guidance of ICRP Publication 111.
AB  - The International Commission on Radiological Protection provides guidance for the
      protection of people living in long-term contaminated areas after nuclear
      accidents or radiological emergencies in ICRP Publication 111 (Ann. ICRP 2009,
      39(3)). The prolonged exposures resulting from such events are defined as
      existing exposure situations and the driving principle for managing exposure
      situations is the optimization of protection. In conjunction with optimization,
      the Commission recommends the use of reference levels to restrict individual
      doses. To be effective, protection strategies to maintain and reduce exposure as
      low as reasonably achievable should include actions implemented by public
      authorities and private businesses, but also by the affected population itself.
      The process through which inhabitants living in a contaminated environment
      identify problems and apply their own protective actions has been named 'self
      help protection' by the Commission. Such a process supposes that affected
      individuals are fully aware of the situation and are well informed. It is the
      responsibility of the authorities to establish programmes for continuous
      radiation monitoring, information and education of the population. The
      involvement of local professionals and inhabitants in the definition and
      implementation of protection strategies is a key factor for the sustainability of
      long-term rehabilitation programmes.

PMID- 22395155
TI  - The pantrochanteric hip fracture:  an iatrogenic entity.

PMID- 22395156
TI  - Pattern of antibiotic use in the community: nuon-adherence and self-prescription
      rates in an Italian urban population.
AB  - The aim of the present study was to assess the pattern of antibiotic use in a
      community setting of an urban area of Italy and identify factors that affect
      adherence to their use. By using a questionnaire-based survey, we collected 1,269
      interviews and performed analysis on those patients who had their last course of
      antibiotic within the past 12 months (956 subjects). Among the subjects reporting
      that they had not followed their last antibiotic course as prescribed, 14.7%
      stopped therapy early, 5.4% modified the dosage, and 5% changed the prescribed
      antibiotic. Approximately 23% of the subjects declared that they self-prescribed
      antibiotics. After adjusting for all covariates, major predictors for the self
      prescription of antibiotics were younger age, female gender and higher
      socioeconomic and educational status. Conversely, both low educational and
      socioeconomic status were associated with a higher risk of non-adherence to
      physician indications. The findings of this study assessed the widespread pattern
      of poor antibiotic-taking behavior and provides important implications for
      understanding the targets of future educational campaigns to control the use and
      misuse of antibiotics.

PMID- 22395157
TI  - Analysis of genome-wide structure, diversity and fine mapping of Mendelian traits
      in traditional and village chickens.
AB  - Extensive phenotypic variation is a common feature among village chickens found
      throughout much of the developing world, and in traditional chicken breeds that
      have been artificially selected for traits such as plumage variety. We present
      here an assessment of traditional and village chicken populations, for fine
      mapping of Mendelian traits using genome-wide single-nucleotide polymorphism
      (SNP) genotyping while providing information on their genetic structure and
      diversity. Bayesian clustering analysis reveals two main genetic backgrounds in
      traditional breeds, Kenyan, Ethiopian and Chilean village chickens. Analysis of
      linkage disequilibrium (LD) reveals useful LD (r(2) >= 0.3) in both traditional
      and village chickens at pairwise marker distances of ~10 Kb; while haplotype
      block analysis indicates a median block size of 11-12 Kb. Association mapping
      yielded refined mapping intervals for duplex comb (Gga 2:38.55-38.89 Mb) and rose
      comb (Gga 7:18.41-22.09 Mb) phenotypes in traditional breeds. Combined mapping
      information from traditional breeds and Chilean village chicken allows the oocyan
      phenotype to be fine mapped to two small regions (Gga 1:67.25-67.28 Mb, Gga
      1:67.28-67.32 Mb) totalling ~75 Kb. Mapping the unmapped earlobe pigmentation
      phenotype supports previous findings that the trait is sex-linked and polygenic.
      A critical assessment of the number of SNPs required to map simple traits
      indicate that between 90 and 110K SNPs are required for full genome-wide analysis
      of haplotype block structure/ancestry, and for association mapping in both
      traditional and village chickens. Our results demonstrate the importance and
      uniqueness of phenotypic diversity and genetic structure of traditional chicken
      breeds for fine-scale mapping of Mendelian traits in the species, with village
      chicken populations providing further opportunities to enhance mapping
      resolutions.

PMID- 22395158
TI  - Domesticated species form a treasure-trove for molecular characterization of
      Mendelian traits by exploiting the specific genetic structure of these species in
      across-breed genome wide association studies.

PMID- 22395159
TI  - Emergency medical preparedness for radiological/nuclear incidents in the United
      States.
AB  - The Office of the Assistant Secretary for Preparedness and Response in the
      Department of Health and Human Services develops health and medical response
      plans for all hazards--natural and human caused. While a nuclear power plant
      (NPP) incident will take time to evolve, a terrorist incident will have 'no
      notice' so that extensive preparation and planning are essential. For
      radiological/nuclear (rad/nuc) incidents we have developed and continue to refine
      detailed plans and tools for medical responders for a nuclear detonation and a
      radiological dispersal device, which also serve for any type of rad/nuc incident.
      The plans are based on the best available basic science with the goal of
      providing planners and responders with just-in-time information and tools. There
      is much in common across the range of hazards, so that the products developed for
      rad/nuc incidents have helped overall preparedness. A major consideration in the
      development of new diagnostics, medical treatment and countermeasures for
      radiation injury is that of 'dual utility' with potential for routine medical use
      for cancer care. Participation and collaboration among nations helping the
      Japanese response to the Fukushima earthquake, tsunami and NPP disaster
      demonstrated the benefit of preparation and ongoing worldwide cooperation among
      experts.

PMID- 22395160
TI  - Combining weak affinity chromatography, NMR spectroscopy and molecular
      simulations in carbohydrate-lysozyme interaction studies.
AB  - By examining the interactions between the protein hen egg-white lysozyme (HEWL)
      and commercially available and chemically synthesized carbohydrate ligands using
      a combination of weak affinity chromatography (WAC), NMR spectroscopy and
      molecular simulations, we report on new affinity data as well as a detailed
      binding model for the HEWL protein. The equilibrium dissociation constants of the
      ligands were obtained by WAC but also by NMR spectroscopy, which agreed well. The
      structures of two HEWL-disaccharide complexes in solution were deduced by NMR
      spectroscopy using (1)H saturation transfer difference (STD) effects and
      transferred (1)H,(1)H-NOESY experiments, relaxation-matrix calculations,
      molecular docking and molecular dynamics simulations. In solution the two
      disaccharides beta-d-Galp-(1->4)-beta-D-GlcpNAc-OMe and beta-D-GlcpNAc-(1->4)
      beta-D-GlcpNAc-OMe bind to the B and C sites of HEWL in a syn-conformation at the
      glycosidic linkage between the two sugar residues. Intermolecular hydrogen
      bonding and CH/pi-interactions form the basis of the protein-ligand complexes in
      a way characteristic of carbohydrate-protein interactions. Molecular dynamics
      simulations with explicit water molecules of both the apo-form of the protein and
      a ligand-protein complex showed structural change compared to a crystal structure
      of the protein. The flexibility of HEWL as indicated by a residue-based root-mean
      square deviation analysis indicated similarities overall, with some residue
      specific differences, inter alia, for Arg61 that is situated prior to a flexible
      loop. The Arg61 flexibility was notably larger in the ligand-complexed form of
      HEWL. N,N'-Diacetylchitobiose has previously been observed to bind to HEWL at the
      B and C sites in water solution based on (1)H NMR chemical shift changes in the
      protein whereas the disaccharide binds at either the B and C sites or the C and D
      sites in different crystal complexes. The present study thus highlights that
      protein-ligand complexes may vary notably between the solution and solid states,
      underscoring the importance of targeting the pertinent binding site(s) for
      inhibition of protein activity and the advantages of combining different
      techniques in a screening process.

PMID- 22395161
TI  - Keep it real.

PMID- 22395163
TI  - BRA Day.

PMID- 22395164
TI  - Introduction to social media.

PMID- 22395168
TI  - Current advances in facial reconstructive surgery following head and neck cancer
      surgery.
AB  - There are currently a number of options in routine clinical use for facial
      reconstruction following ablative procedures, as well as several budding advances
      that may provide alternative approaches in the future. This review aims to give
      an overview of the current status of facial reconstruction as well as an
      introduction to the new developments.

PMID- 22395170
TI  - The art of the aesthetic consultation.
AB  - Aging may be one of the most foreseeable facts of life. As aesthetic providers,
      we routinely hear concerns about facial aging, and it is important that we
      address these concerns by consistently delivering the best care possible while
      managing our clients' expectations. How do we set our clients and ourselves up
      for success by providing superb aesthetic solutions to the age-old challenges we
      are faced with every day? A thorough Aesthetic Analysis of the clients' needs and
      an Aesthetic Plan to their specific needs ensure success. An Aesthetic Plan
      requires a shift from a two-dimensional approach to a three-dimensional approach.
      Providing safe treatments, establishing trust, producing positive outcomes, and
      creating engaging experiences will ensure loyalty, future treatments, and
      continued maintenance.

PMID- 22395172
TI  - Ethical and legal considerations in teen aesthetic surgery.

PMID- 22395173
TI  - SOCIAL MEDIA--risk management.
AB  - Approximately 8% of the world's population and 42.3% of the entire American
      population are on Facebook. About 9% of the adult U.S. internet population has
      used Twitter as of the end of 2010. More than 200 million people currently access
      Facebook through their mobile devices. LinkedIn has more than 100 million users
      worldwide. There are more than 2 billion video views on YouTube everyday. These
      staggering statistics point to the fact that social media is an integral part of
      our lives, and that it is here to stay.

PMID- 22395174
TI  - Best technique for obtaining wound cultures.
AB  - Infection is a major impairment in delayed and nonhealing chronic wounds.
      Cultures of chronic wounds are not routinely performed unless there is a clinical
      suspicion of infection. The culture is then indicated to identify the causative
      organism and to guide antibiotic therapy, systematically and topically. The deep
      tissue biopsy is regarded as the gold standard for identification of wound
      bioburden and clinical infection. However, controversy persists among
      practitioners as to the relevancy of doing cultures and the technique to use.
      This article will explore the various techniques used in clinical practice to
      obtain cultures for diagnosing wound infections.

PMID- 22395175
TI  - Emergency preparedness case study--tachycardia.

PMID- 22395176
TI  - On the efficiency and correction of vertically oriented blunt bioaerosol samplers
      in moving air.
AB  - The aspiration efficiency of vertical and wind-oriented Air-O-Cell samplers was
      investigated in a field study using the pollen of hazel, sweet chestnut and
      birch. Collected pollen numbers were compared to measurements of a Hirst-type
      Burkard spore trap. The discrepancy between pollen counts is substantial in the
      case of vertical orientation. The results indicate a strong influence of wind
      velocity and inlet orientation relative to the freestream on the aspiration
      efficiency. Various studies reported on inertial effects on aerosol motion as
      function of wind velocity. The measurements were compared to a physically based
      model for the limited case of vertical blunt samplers. Additionally, a simple
      linear model based on pollen counts and wind velocity was developed. Both
      correction models notably reduce the error of vertically oriented samplers,
      whereas only the physically based model can be used on independent datasets. The
      study also addressed the precision error of the instruments used, which was
      substantial for both sampler types.

PMID- 22395178
TI  - A theoretical study of the sum frequency vibrational spectroscopy of the carbon
      tetrachloride/water interface.
AB  - Theoretical approximations to the sum frequency vibrational spectroscopy (SFVS)
      of the carbon tetrachloride/water interface are constructed using the quantum
      corrected time correlation functions (TCF) to aid in interpretation of
      experimental data and to predict novel vibrational modes. Instantaneous normal
      mode (INM) methods are used to characterize the observed modes leading to the TCF
      signal, thus providing molecular resolution of the vibrational lineshapes.
      Detailed comparisons of the theoretical signals are made with those obtained
      experimentally and show excellent agreement for the spectral peaks in the O-H
      stretching region of water. An intermolecular mode, unique to the interface, at
      848 cm(-1) is also identifiable, similar to the one seen for the water/vapor
      interface. INM analysis reveals the resonance is due to a wagging mode (hindered
      rotation) that was previously identified (Perry et al 2005 J. Chem. Phys. 123
      144705) as localized on a single water molecule with both hydrogens displaced
      normal to the interface-generally it is found that the symmetry breaking at the
      interface leads to hindered translations and rotations at hydrophilic/hydrophobic
      interfaces that assume finite vibrational frequencies due to anchoring at the
      aqueous interface. Additionally, examination of the real and imaginary parts of
      the theoretical SFVS spectra reveal the spectroscopic species attributed the
      resonances and possible subspecies in the O-H region; these results are
      consistent with extant experimental data and associated analysis.

PMID- 22395179
TI  - A portable and integrated nucleic acid amplification microfluidic chip for
      identifying bacteria.
AB  - In this work, we developed a portable integrated microchip of loop-mediated
      isothermal nucleic acid amplification (LAMP). This chip, with sample-to-answer
      capability, could perform rapid DNA release, exponential signal amplification and
      naked-eye result read-out in single or multiplex format. We call it iMULAMP,
      namely integrated micro-LAMP, which was successfully used for point-of-care
      identification of bacteria.

PMID- 22395180
TI  - The single-cell chemostat: an agarose-based, microfluidic device for high
      throughput, single-cell studies of bacteria and bacterial communities.
AB  - Optical microscopy of single bacteria growing on solid agarose support is a
      powerful method for studying the natural heterogeneity in growth and gene
      expression. While the material properties of agarose make it an excellent
      substrate for such studies, the sheer number of exponentially growing cells
      eventually overwhelms the agarose pad, which fundamentally limits the duration
      and the throughput of measurements. Here we overcome the limitations of
      exponential growth by patterning agarose pads on the sub-micron-scale. Linear
      tracks constrain the growth of bacteria into a high density array of linear micro
      colonies. Buffer flow through microfluidic lines washes away excess cells and
      delivers fresh nutrient buffer. Densely patterned tracks allow us to cultivate
      and image hundreds of thousands of cells on a single agarose pad over 30-40
      generations, which drastically increases single-cell measurement throughput. In
      addition, we show that patterned agarose can facilitate single-cell measurements
      within bacterial communities. As a proof-of-principle, we study a community of E.
      coli auxotrophs that can complement the amino acid deficiencies of one another.
      We find that the growth rate of colonies of one strain decreases sharply with the
      distance to colonies of the complementary strain over distances of only a few
      cell lengths. Because patterned agarose pads maintain cells in a chemostatic
      environment in which every cell can be imaged, we term our device the single-cell
      chemostat. High-throughput measurements of single cells growing chemostatically
      should greatly facilitate the study of a variety of microbial behaviours.

PMID- 22395181
TI  - What type of probiotic was used?

PMID- 22395184
TI  - Treatment of bleeding after kidney biopsy with recombinant activated factor VII.
AB  - Recombinant activated factor VII (rFVIIa) is approved for prevention and
      treatment of bleeding in hemophilia patients with inhibitors to FVIII (hemophilia
      A) or IX (hemophilia B), patients with congenital and acquired hemophilia and in
      patients with FVII deficiency or Glantzmann thrombasthenia (last indication is
      approved only in Europe). Off-labeled, the drug has been prescribed for
      prevention, or treatment of bleeding in severe hepatic disease, neonatal
      coagulopathies, high-risk surgical procedures, trauma, thrombocytopenia and
      platelet function disorders, as well as for urgent reversal of oral
      anticoagulation. Here we report a case of a 53-year-old female patient with
      delayed graft function after kidney transplantation, who had kidney biopsy
      complicated with prolonged bleeding. After unsuccessful treatment with
      desmopressin, the patient was treated with rFVIIa and the bleeding stopped
      immediately. Only few anecdotal reports of use of rFVIIa for treatment of
      bleeding in uremic patients have been published thus far. To our knowledge, this
      is the first case that describes use of rFVIIa for management of bleeding as a
      complication of renal biopsy in a uremic patient in the early kidney
      posttransplantation period.

PMID- 22395185
TI  - Biochemical, mechanical, and morphological properties of a completely autologous
      platelet-rich wound sealant.
AB  - The optimal composition of fibrin sealant preparations is not known. We,
      therefore, sought to construct a series of sealants from autologous components
      and compare their functioning to Bioseal a commonly used sealant. Characteristics
      of the platelet-rich plasma, cryoprecipitate, and thrombin were determined and
      compared to commercial glue from composition, function, and microscopy aspects.
      The concentrations of platelets as well as fibronectin in autologous fibrin glues
      were significantly higher than those in commercial ones (P < 0.001). Mechanical
      values (maximum amplitude and clot strength) obtained from thrombelastograph
      assays in two groups were not significantly different (P > 0.05). A dense
      platelet surface and fibrin net structures could be observed in the autologous
      samples, whereas there were only sparse fibrin nets without cellular components
      in Bioseal. Characterization of autologous and Bioseal fibrin sealants and their
      performance do not have significant difference in biochemical and mechanical
      properties. The entirely autologous platelet-rich gel in the present study may
      get wide application in future practice after confirmation of its safety,
      efficiency, and economic benefits.

PMID- 22395186
TI  - Colonic perforation after rituximab treatment for posttransplant
      lymphoproliferative disorder.

PMID- 22395187
TI  - Quantitative analysis of intestinal bacterial populations from term infants fed
      formula supplemented with fructo-oligosaccharides.
AB  - OBJECTIVES: Previous studies of infant formulas supplemented with
      oligosaccharides reported mixed results regarding the impact on intestinal
      microbial populations. The objective of this study was to examine the effect of
      supplementation of an infant formula with fructo-oligosaccharides (FOS) on select
      groups of intestinal bacteria in term infants. METHODS: Four groups of infants
      were enrolled and fed human milk, a commercially available milk-based infant
      formula, or infant formula supplemented with 2.0 or 3.0 g/L FOS. Dietary intake,
      stool, and tolerance events were recorded. Fresh stool samples were collected
      approximately 27 days after feeding the diets (approximately 32 days after
      birth). Total bacteria, Bacteroides (as commensal bacteria), Bifidobacterium and
      Lactobacillus, and Clostridium difficile and Escherichia coli were quantified
      using respective specific real-time PCR assays. RESULTS: The formula feeding
      groups did not differ in stool consistency and stool frequency or frequency of
      spit-up or vomit during the entire study. The formula-fed infants tended to have
      more total bacteria in their stool samples than the human milk-fed infants. The
      formula-fed infants harbored a greater abundance of C difficile and E coli than
      the human milk-fed infants, but had a similar abundance of Bacteroides,
      Bifidobacterium, and Lactobacillus. The FOS supplementation at either dose did
      not significantly increase the bifidobacterial or lactobacilli populations, or
      decrease the populations of C difficile, E coli, or Bacteroides. CONCLUSIONS: The
      milk-based formula used in this study supported bifidobacterial and lactobacilli
      populations comparable with the human milk group; however, this formula did not
      suppress E coli or C difficile as effectively as human milk.

PMID- 22395188
TI  - Diagnosis of nonalcoholic fatty liver disease in children and adolescents:
      position paper of the ESPGHAN Hepatology Committee.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic
      liver disease in children and adolescents in the United States, and most probably
      also in the rest of the industrialized world.As the prevalence of NAFLD in
      childhood increases with the worldwide obesity epidemic, there is an urgent need
      for diagnostic standards that can be commonly used by pediatricians and
      hepatologists. To this end, we performed a PubMed search of the adult and
      pediatric literature on NAFLD diagnosis through May 2011 using Topics and/or
      relevant Authors as search words. According to the present literature, NAFLD is
      suspected based on the association of fatty liver combined with risk factors
      (mainly obesity), after the exclusion of other causes of liver disease. The
      reference but imperfect standard for confirming NAFLD is liver histology. The
      following surrogate markers are presently used to estimate degree of steatosis
      and liver fibrosis and risk of progression to end-stage liver disease: imaging by
      ultrasonography or magnetic resonance imaging, liver function tests, and serum
      markers of liver fibrosis.NAFLD should be suspected in all of the overweight or
      obese children and adolescents older than 3 years with increased waist
      circumference especially if there is a NAFLD history in relatives. The typical
      presentation, however, is in children ages 10 years and older. The first
      diagnostic step in these children should be abdominal ultrasound and liver
      function tests, followed by exclusion of other liver diseases. Overweight/obese
      children with normal ultrasonographic imaging and normal liver function tests
      should still be monitored due to the poor sensitivity of these tests at a single
      assessment.Indications for liver biopsy include the following: to rule out other
      treatable diseases, in cases of clinically suspected advanced liver disease,
      before pharmacological/surgical treatment, and as part of a structured
      intervention protocol or clinical research trial.

PMID- 22395189
TI  - Preoperative immunosuppression is not associated with increased postoperative
      complications following colectomy in children with colitis.
AB  - OBJECTIVES: The aim of the present study was to review postoperative
      complications of pediatric patients undergoing colectomy for ulcerative colitis
      (UC) or inflammatory bowel disease-unspecified (IBD-U) with a focus on
      preoperative immunosuppression including exposure to infliximab. METHODS: We
      performed a retrospective chart review of all of the children with UC or IBD-U
      undergoing colectomy at our institution from 1996 to 2010. Data collected
      included indication for colectomy, immunosuppressive medications taken within 30
      to 90 days of colectomy, surgical techniques and staging, and early and late
      postoperative complications. RESULTS: A total of 51 patients underwent colectomy
      (45 UC, 6 IBD-U) (55% male, 63% pancolitis at diagnosis, mean age at diagnosis
      10.8 +/- 3.8 years, mean age at colectomy 13.1 +/- 3.8 years). Indications for
      colectomy were fulminant colitis in 26% and medically refractory chronic disease
      in 74%. Patient exposure to immunosuppression in the 30 days before colectomy
      included corticosteroids (88%), thiopurines (51%), and calcineurin inhibitors
      (4%). Within 90 days before colectomy, 65% of patients were exposed to
      infliximab. Small bowel obstruction was the most common postoperative
      complication, occurring in 19% (treated surgically in 30%), followed by wound
      infection in 8% and intraabdominal abscess in 6%. One patient developed
      postoperative sepsis. There was no increased incidence of early or late
      infectious or noninfectious complications in those patients taking or not taking
      thiopurines or calcineurin inhibitors (within 30 days), or infliximab (within 90
      days). CONCLUSIONS: Preoperative exposure to thiopurines or calcineurin
      inhibitors (within 30 days) or infliximab (within 90 days) was not associated
      with increased postoperative complications in our cohort undergoing colectomy for
      UC or IBD-U.

PMID- 22395190
TI  - Prevention of rotavirus-induced diarrhea by preferential secretion of IgA in
      breast milk via maternal administration of Lactobacillus gasseri SBT2055.
AB  - OBJECTIVES: Rotavirus (RV)-induced diarrhea poses a major health problem,
      particularly to infants. An effective measure to prevent RV infection is to
      consume breast milk with higher levels of protective IgA. We therefore examined
      whether Lactobacillus gasseri SBT2055 (LG2055) could augment immunoglobulin (Ig)
      A levels and reduce the incidence of diarrhea in a mouse model of RV infection.
      METHODS: Female BALB/c mouse dams were fed a diet containing 0.1% heat-treated
      LG2055 or a control, beginning 4 weeks before mating with male mice and
      continuing until the experiment ended. One week after mating, female dams were
      immunized orally with simian RV SA-11. Five days after birth, mouse pups were
      infected orally with RV and the incidence of diarrhea was determined 4 days
      later. RV-specific and total IgA were quantified by an enzyme-linked
      immunosorbent assay. RESULTS: LG2055-fed dams immunized with RV (LG2055/RV)
      secreted breast milk that significantly lowered the incidence of RV-induced
      diarrhea in their pups as compared with dams immunized with RV alone (C/RV). The
      LG2055/RV dams also produced a significantly greater amount of RV-specific IgA in
      breast milk obtained from the pups' stomach, but not in feces or Peyer's patch
      cell cultures. In addition, LG2055 stimulated total IgA production in splenocyte
      cultures from Toll-like receptor (TLR)-4-knockout mice, but not those from TLR-2
      knockouts. CONCLUSIONS: LG2055-fed dams reduced RV infection in their pups and
      elevated RV-specific IgA levels in breast milk of stomach origin, the possible
      mechanism of which may be TLR-2 stimulation by LG2055.

PMID- 22395191
TI  - Prevention of rotavirus-induced diarrhea.

PMID- 22395192
TI  - A self-consistent field study of a hydrocarbon droplet at the air-water
      interface.
AB  - A molecularly detailed self-consistent field (SCF) approach is applied to
      describe a sessile hydrocarbon droplet placed at the air-water interface.
      Predictions of the contact angle for macroscopic droplets follow from using
      Neumann's equation, wherein the macroscopic interfacial tensions are computed
      from one-gradient calculations for flat interfaces. A two-gradient cylindrical
      coordinate system with mirror-like boundary conditions is used to analyse the
      three dimensional shape of the nano-scale oil droplet at the air-water interface.
      These small droplets have a finite value of the Laplace pressure and concomitant
      line tension. It has been calculated that the oil-water and oil-vapour
      interfacial tensions are curvature dependent and increase slightly with
      increasing interfacial curvature. In contrast, the line tension tends to decrease
      with curvature. In all cases there is only a weak influence of the line tension
      on the droplet shape. We therefore argue that the nano-scale droplets, which are
      described in the SCF approach, are representative for macroscopic droplets and
      that the method can be used to efficiently generate accurate information on the
      spreading of oil droplets at the air-water interface in molecularly more complex
      situations. As an example, non-ionic surfactants have been included in the system
      to illustrate how a molecularly more complex situation will change the wetting
      properties of the sessile drop. This short forecast is aimed to outline and to
      stress the potential of the method.

PMID- 22395193
TI  - Radiation epidemiology: a perspective on Fukushima.
AB  - For nearly 100 years, epidemiologic studies of human populations exposed to
      ionising radiation have provided quantitative information on health risks. High
      dose deterministic (tissue reaction) effects result when sufficient numbers of
      functioning cells are killed, such as in bone marrow depression that can lead to
      death. Lower dose stochastic effects are probabilistic in nature and include an
      increased risk of cancer later in life and heritable genetic defects, although
      genetic conditions in the children of irradiated parents have yet to be
      convincingly demonstrated. Radiation studies are of diverse populations and
      include not only the Japanese atomic bomb survivors, but also patients treated
      with radiation for malignant and non-malignant disease; patients exposed for
      diagnostic purposes; persons with intakes of radionuclides; workers
      occupationally exposed; and communities exposed to environmental and accidentally
      released sources of radiation. Much is known about radiation and its risks. The
      major unanswered question in radiation epidemiology, however, is not whether
      radiation causes cancer, but what the level of risk is following low dose (<100
      mSv) or low dose rate exposures. Paracelsus is credited with first articulating
      that the 'poison is in the dose', which for radiation epidemiology translates as
      'the lower the dose, the lower the risk' and, an important corollary, the lower
      the dose, the greater the difficulty in detecting any increase in the number of
      cancers possibly attributable to radiation. In contrast to the Chernobyl reactor
      accident, the Fukushima reactor accident has to date resulted in no deterministic
      effects and no worker deaths. Estimates to date of population doses suggest very
      low uptakes of radioactive iodine which was a major determinant of the epidemic
      of thyroid cancer following childhood exposures around Chernobyl. The estimates
      to date of population doses are also much lower (and the distribution much
      narrower) than the doses for which cancer excesses have been detected among
      atomic bomb survivors after 60 years of follow-up. Studies of populations exposed
      to low doses are also limited in their ability to account for important lifestyle
      factors, such as cigarette smoking and medical x-ray exposures, which could
      distort findings. Studies of the Fukushima population should be and are being
      considered for reassurance and health care reasons. Apart from as regards the
      extreme psychological stress caused by the horrific loss of life following the
      tsunami and the large-scale evacuation from homes and villages, such studies have
      limited to no chance of providing information on possible health risks following
      low dose exposures received gradually over time--the estimated doses (to date)
      are just too small.

PMID- 22395194
TI  - Induced circular dichroism of stereoregular vinyl polymers.
AB  - Stereoregular vinyl polymers, poly(2-vinyl pyridine)s (P2VPs), were synthesized
      to examine the tacticity effect on the induced circular dichroism (ICD) via
      association with chiral acids. The ICD was found to be strongly dependent on the
      isotacticity of the P2VPs and the acidity of chiral acid in addition to its
      bulkiness.

PMID- 22395195
TI  - Investigation of angiogenetic pathways in nasal polyposis.
AB  - Tissue angiogenesis is a complex phenomenon that results in the growth of new
      blood vessels from the microcirculation. This process has been known to play a
      crucial role in tumor growth as well as several benign diseases. The aim of this
      study was to assess mRNA expression of various angiogenic factors and chemokines
      in nasal polyps and compare the results to normal nasal mucosa. mRNA expression
      was measured using real-time RT-PCR for the following angiogenic factors and
      chemokines: VEGF, VEGFR-1, Ang-1, Ang-2, Tie-2A, Tie-2B, SDF-1alpha, SDF-1beta,
      CXCR4 and YY1. Biopsy specimens from nasal polyps in the polyposis group and
      middle turbinates in the control group were studied. A total of 18 nasal
      polyposis patients were studied and compared to 10 control subjects. Results
      showed VEGF, VEGFR-1, Ang-1, Ang-2, Tie-2A, Tie-2B, SDF-1alpha and SDF-1beta mRNA
      expression to be significantly higher in nasal polyposis patients compared to the
      control group (p<0.05). The findings of this study support the role of angiogenic
      growth factors in the pathogenesis of nasal polyposis. Further studies are
      required to confirm these results and evaluate potential clinical implications.

PMID- 22395196
TI  - Efficacy and safety of a modified dosage regimen of nesiritide in patients older
      than 75 years with acute heart failure.
AB  - BACKGROUND AND AIMS: To explore efficacy and safety of a modified dosage regimen
      of nesiritide in patients (>=75 years) with acute heart failure (AHF). METHODS:
      Total 140 patients (>=75 years) with AHF were enrolled in this study. They were
      randomly and evenly divided into two group--control and nesiritide group. The
      control group received only conventional treatment for AHF, while the nesiritide
      group received conventional treatment plus a continual intravenous infusion of
      nesiritide at a rate of 0.0075-0.015 MUg.kg(-1).min(-1) for 10-15 hours (total
      0.5- 1.0 mg) once daily for 13 days. RESULTS: Medical research council scales in
      nesiritide group were significantly lower than those in control group on day 4, 8
      and 14. Scores of edema had no significant difference, but were lower in
      nesiritide group on day 8 and 14. The nesiritide group had markedly more net body
      fluid losses. NT-proBNP, serum creatinine, blood pressure, cTnI, 30-day and 60
      day mortality had no significant difference between two groups. CONCLUSIONS:
      Nesiritide resulted in improvements in dyspnea and edema, and similar adverse
      effects compared with conventional treatment. In spite of no reduction on short
      term mortality and a reversible influence on renal function, nesiritide was still
      an important choice for the elderly (>=75 years) with AHF.

PMID- 22395197
TI  - Reproducible mouse sciatic nerve crush and subsequent assessment of regeneration
      by whole mount muscle analysis.
AB  - Regeneration in the peripheral nervous system (PNS) is widely studied both for
      its relevance to human disease and to understand the robust regenerative response
      mounted by PNS neurons thereby possibly illuminating the failures of CNS
      regeneration(1). Sciatic nerve crush (axonotmesis) is one of the most common
      models of peripheral nerve injury in rodents(2). Crushing interrupts all axons
      but Schwann cell basal laminae are preserved so that regeneration is
      optimal(3,4). This allows the investigator to study precisely the ability of a
      growing axon to interact with both the Schwann cell and basal laminae(4). Rats
      have generally been the preferred animal models for experimental nerve crush.
      They are widely available and their lesioned sciatic nerve provides a reasonable
      approximation of human nerve lesions(5,4). Though smaller in size than rat nerve,
      the mouse nerve has many similar qualities. Most importantly though, mouse models
      are increasingly valuable because of the wide availability of transgenic lines
      now allows for a detailed dissection of the individual molecules critical for
      nerve regeneration(6, 7). Prior investigators have used multiple methods to
      produce a nerve crush or injury including simple angled forceps, chilled forceps,
      hemostatic forceps, vascular clamps, and investigator-designed
      clamps(8,9,10,11,12). Investigators have also used various methods of marking the
      injury site including suture, carbon particles and fluorescent beads(13,14,1). We
      describe our method to obtain a reproducibly complete sciatic nerve crush with
      accurate and persistent marking of the crush-site using a fine hemostatic forceps
      and subsequent carbon crush-site marking. As part of our description of the
      sciatic nerve crush procedure we have also included a relatively simple method of
      muscle whole mount we use to subsequently quantify regeneration.

PMID- 22395198
TI  - Improper waste disposal of silver-mercury amalgam.
AB  - The objective of this work was to estimate the quantity of mercury residue
      present in dental amalgam that is generated and discarded in the city of Manaus
      (Amazon-Brazil). For this purpose, the locations of amalgam usage (10 public and
      31 private dental clinics), the method by which the residue is discarded (14
      clinics improper disposal), and the analysis of total mercury in the sediment of
      the controlled landfill (2.68-3 MUgHg/g), were described. It was concluded that:
      there are dental clinics in the city that discard mercury residue into the common
      waste disposal system, which contravenes health safety standards.

PMID- 22395199
TI  - Phytotoxicity of arsenate and salinity on early seedling growth of rice (Oryza
      sativa L.): a threat to sustainable rice cultivation in South and South-East
      Asia.
AB  - Arsenic (As) contamination is an important environmental consequence in some
      parts of salinity-affected South (S) and South-East (SE) Asia. In this study, we
      investigated the individual and combined phytotoxicity of arsenic (As) [arsenate;
      As(V)] and salinity (NaCl) on early seedling growth (ESG) of saline-tolerant and
      non-tolerant rice varieties. Germination percentage (GP), germination speed (GS)
      and vigor index (VI) of both saline-tolerant and non-tolerant rice varieties
      decreased significantly (p > 0.01) with increasing As(V) and NaCl concentrations.
      The highest GP (91%) was observed for saline non-tolerant BRRI dhan28 and BRRI
      dhan49, while the lowest (62%) was for saline-tolerant BRRI dhan47. The ESG
      parameters, such as weights and relative lengths of plumule and radicle, also
      decreased significantly (p < 0.01) with increasing As(V) and NaCl concentrations.
      Relative radicle length was more affected than plumule length by As(V) and NaCl.
      Although VI of saline-tolerant and non-tolerant rice seedlings showed significant
      variation (p < 0.05), weights and lengths of plumule and radicle of different
      rice varieties did not show significant variation for As(V) and NaCl treatments.
      Results reveal that the combined phytotoxicity of As(V) and NaCl on rice seed
      germination and ESG are greater than their individual toxicities, and some saline
      tolerant rice varieties are more resistant to the combined phytotoxicity of As(V)
      and NaCl than the saline non-tolerant varieties.

PMID- 22395200
TI  - Imidacloprid affects Pardosa pseudoannulata adults and their unexposed offspring.
AB  - Imidacloprid is a nicotine-based, systemic, widely used insecticide. In order to
      investigate the effects of imidacloprid on the spider Pardosa pseudoannulata
      (Araneae: Lycosidae), specimens were exposed to different concentrations of
      imidacloprid (12.5, 25, 50, 100, 200 mg/L) by the dipping method. Surviving
      spiders were used to determine the fecundity, development time of unexposed
      offspring, predation, and the activities of detoxification enzymes. Significant
      reductions were observed in survival rate and fecundity of spiders exposed to
      imidacloprid. The development times of unexposed offspring (F(1)) were prolonged
      significantly with increased concentrations of imidacloprid. Spiders exposed to
      concentrations of imidacloprid above 25 mg/L showed significantly weaker
      predation on Drosophila melanogaster than the control group, but a low dose of
      imidacloprid (12.5 mg/L) increased predation ability. The activities of carboxyl
      esterase, acetyl cholinesterase, and the mixed-function oxidase were
      significantly inhibited by imidacloprid. With increasing concentrations of
      imidacloprid, the activities of all three kinds of enzymes were decreased
      significantly. These results suggest that imidacloprid can stimulate the
      performance of spiders (in low concentration) and has chronic toxicity to the
      spiders.

PMID- 22395202
TI  - Enhanced depth imaging optical coherence tomography of the choroid in recurrent
      unilateral posterior scleritis.

PMID- 22395201
TI  - Synthesis, staining properties, and biocompatibility of a new cyanine dye for ILM
      peeling.
AB  - BACKGROUND: The aim of this work is to investigate the biocompatibility and
      staining properties of DSS: 3,3'-Di-(4-sulfobutyl)-1,1,1',1'-tetramethyl-di-1H
      benz[e]indocarbocyanine (DSS). METHODS: Dye concentrations of 0.5, 0.25, and 0.1%
      were evaluated (290 and 295 mOsm). Toxicity was assessed using a colorimetric
      test measuring the inhibition of ARPE 19 cell, human primary RPE cell, and human
      Muller cell proliferation. Exposure time was 30, 60, 120, and 300 s. Indocyanine
      green (ICG) (0.5, 0.25, and 0.1%) served as a control. Cells were also
      illuminated with plain white light (750 mW/cm(2)) for 10 min to assess phototoxic
      effects. Besides staining of porcine and human lens capsule, internal limiting
      membrane (ILM)-staining was assessed by applying 0.25 and 0.5% DSS over the
      macula in two human post-mortem eyes. RESULTS: DSS of 0.25 and 0.1% showed no
      toxic effect on primary RPE cells and MIO-M1cells, and 0.5, 0.25, and 0.1% for
      ARPE-19 cells. In MIO-M1cells, 0.5% dye showed a significant reduction of
      mitochondrial dehydrogenase activity only following an exposure time of 300 s.
      Following illumination, ICG showed a significantly more pronounced effect on cell
      viability in primary RPE cells and MIO-M1cells compared to DSS. The absorption
      maximum is found at 591 nm; the even more bathochromic fluorescence proceeds with
      a common Stokes' shift where maxima at 620 and 660 nm with a quantum yield of 32%
      were found. The fluorescence is sufficiently hypsochromic and the fluorescence
      quantum yield high enough for an easy visual detection. The contrast and staining
      properties at the ILM were excellent and allowed for a controlled removal of the
      ILM during surgery. No penetration into deeper retinal layers was noted.
      CONCLUSIONS: Our results indicate that this new cyanine dye DSS may represent an
      alternative for ILM staining due to its matched absorption concerning visibility
      and fluorescence qualities as well as its good biocompatibility.

PMID- 22395203
TI  - Wavy and elevated retinal pigment epithelial line in optical coherence
      tomographic images of eyes with atypical Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: We report the changes of the retinal pigment epithelium (RPE) determined
      by optical coherence tomography in a patient with atypical Vogt-Koyanagi-Harada
      (VKH) disease during the recovery phase. METHOD: Case presentation. RESULTS: A 74
      year-old woman presented with a central scotoma associated with disc hyperemia,
      serous retinal detachment, and scleral thickening in her left eye, and was
      diagnosed with VKH. OCT showed a serous retinal detachment and a wavy RPE contour
      that corresponded to the choroidal folds. The OCT images clearly showed the
      dynamic changes of the retina, RPE, and choroid during the recovery phase.
      CONCLUSIONS: The OCT was found to be more sensitive in detecting the choroidal
      folds than angiography. OCT images are valuable not only in the diagnosis, but
      also for monitoring the morphology of the retina and choroid during the course of
      VKH.

PMID- 22395205
TI  - Probing platinum degradation in polymer electrolyte membrane fuel cells by
      synchrotron X-ray microscopy.
AB  - Synchrotron-based scanning transmission X-ray spectromicroscopy (STXM) was used
      to characterize the local chemical environment at and around the platinum
      particles in the membrane (PTIM) which form in operationally tested (end-of-life,
      EOL) catalyst coated membranes (CCMs) of polymer electrolyte membrane fuel cells
      (PEM-FC). The band of metallic Pt particles in operationally tested CCM membranes
      was imaged using transmission electron microscopy (TEM). The cathode catalyst
      layer in the beginning-of-life (BOL) CCMs was fabricated using commercially
      available catalysts created from Pt precursors with and without nitrogen
      containing ligands. The surface composition of these catalyst powders was
      measured by X-ray Photoelectron Spectroscopy (XPS). The local chemical
      environment of the PTIM in EOL CCMs was found to be directly related to the Pt
      precursor used in CCM fabrication. STXM chemical mapping at the N 1s edge
      revealed a characteristic spectrum at and around the dendritic Pt particles in
      CCMs fabricated with nitrogen containing Pt-precursors. This N 1s spectrum was
      identical to that of the cathode and different from the membrane. For CCM samples
      fabricated without nitrogen containing Pt-precursors the N 1s spectrum at the Pt
      particles was indistinguishable from that of the adjacent membrane. We interpret
      these observations to indicate that nitrogenous ligands in the nitrogen
      containing precursors, or decomposition product(s) from that source, are
      transported together with the dissolved Pt from the cathode into the membrane as
      a result of the catalyst degradation process. This places constraints on possible
      mechanisms for the PTIM band formation process.

PMID- 22395204
TI  - Regional differences in oxygen saturation in retinal arterioles and venules.
AB  - BACKGROUND: Retinal vessel oxygenation saturation measurements have been the
      focus of much attention in recent years as a potential diagnostic parameter in a
      number of ocular and systemic pathologies. This interest has been heightened by
      the ability to measure oxygen saturation in vivo using a photographic technique.
      METHODS: Retinal vessel oxygenation in venules and arterioles of 279 retinal
      vessels of 12 healthy Caucasian participants (mean age: 30 SD (+/- 6) years) were
      measured consecutively three times to evaluate short-term variation in oxygen
      saturation and regional variability of retinal vessel oxygen saturation using
      dual-wavelength technology (Oxymetry Modul, Imedos, Germany). All subjects
      underwent standard optometric assessment including non-contact intra-ocular
      pressure assessment as well as having their systemic blood pressure measured.
      RESULTS: Vessels were grouped as either near-macula or peripheral, depending on
      their location. Peripheral arterioles and venules exhibited significantly lower
      oxygen saturation compared to their near-macula counterparts (arterioles: 94.7%
      (SD 3.9) vs. 99.7% (SD 3.2); venules: 65.1% (SD 7.2) vs. 90.3% (SD 6.7)). Both
      arterioles and venules, main branches, and those feeding and draining the retina
      near the macula and periphery showed low short-term variability of oxygen
      saturation (arterioles: COV 1.2-1.8%; venules: COV 2.9-4.9%). CONCLUSIONS:
      Retinal arterioles and venules exhibit low short-term variation of oxygen
      saturation in healthy subjects. Regional differences in oxygen saturation could
      be a potential useful marker for risk stratification and diagnostic purposes of
      area-specific retinal pathology such as age-related macula degeneration and
      diabetic maculopathy.

PMID- 22395206
TI  - Large enhancement of perfusion contribution on fMRI signal.
AB  - The perfusion contribution to the total functional magnetic resonance imaging
      (fMRI) signal was investigated using a rat model with mild hypercapnia at 9.4 T,
      and human subjects with visual stimulation at 4 T. It was found that the total
      fMRI signal change could be approximated as a linear superposition of 'true'
      blood oxygenation level-dependent (BOLD; T(2)/T(2)(*)) effect and the blood flow
      related (T(1)) effect. The latter effect was significantly enhanced by using
      short repetition time and large radiofrequency pulse flip angle and became
      comparable to the 'true' BOLD signal in response to a mild hypercapnia in the rat
      brain, resulting in an improved contrast-to-noise ratio (CNR). Bipolar diffusion
      gradients suppressed the intravascular signals but had no significant effect on
      the flow-related signal. Similar results of enhanced fMRI signal were observed in
      the human study. The overall results suggest that the observed flow-related
      signal enhancement is likely originated from perfusion, and this enhancement can
      improve CNR and the spatial specificity for mapping brain activity and physiology
      changes. The nature of mixed BOLD and perfusion-related contributions in the
      total fMRI signal also has implication on BOLD quantification, in particular, the
      BOLD calibration model commonly used to estimate the change of cerebral metabolic
      rate of oxygen.

PMID- 22395209
TI  - Use of spectral analysis with iterative filter for voxelwise determination of
      regional rates of cerebral protein synthesis with L-[1-11C]leucine PET.
AB  - A spectral analysis approach was used to estimate kinetic parameters of the L-[1
      (11)C]leucine positron emission tomography (PET) method and regional rates of
      cerebral protein synthesis (rCPS) on a voxel-by-voxel basis. Spectral analysis
      applies to both heterogeneous and homogeneous tissues; it does not require prior
      assumptions concerning number of tissue compartments. Parameters estimated with
      spectral analysis can be strongly affected by noise, but numerical filters
      improve estimation performance. Spectral analysis with iterative filter (SAIF)
      was originally developed to improve estimation of leucine kinetic parameters and
      rCPS in region-of-interest (ROI) data analyses. In the present study, we
      optimized SAIF for application at the voxel level. In measured L-[1-(11)C]leucine
      PET data, voxel-level SAIF parameter estimates averaged over all voxels within a
      ROI (mean voxel-SAIF) generally agreed well with corresponding estimates derived
      by applying the originally developed SAIF to ROI time-activity curves (ROI-SAIF).
      Region-of-interest-SAIF and mean voxel-SAIF estimates of rCPS were highly
      correlated. Simulations showed that mean voxel-SAIF rCPS estimates were less
      biased and less variable than ROI-SAIF estimates in the whole brain and cortex;
      biases were similar in white matter. We conclude that estimation of rCPS with
      SAIF is improved when the method is applied at voxel level than in ROI analysis.

PMID- 22395208
TI  - Pathophysiology of the neurovascular unit: disease cause or consequence?
AB  - Pathophysiology of the neurovascular unit (NVU) is commonly seen in neurological
      diseases. The typical features of NVU pathophysiology include tissue hypoxia,
      inflammatory and angiogenic activation, as well as initiation of complex
      molecular interactions between cellular (brain endothelial cells, astroctyes,
      pericytes, inflammatory cells, and neurons) and acellular (basal lamina)
      components of the NVU, jointly resulting in increased blood-brain barrier
      permeability, brain edema, neurovascular uncoupling, and neuronal dysfunction and
      damage. The evidence of important role of the brain vascular compartment in
      disease pathogenesis has elicited the debate whether the primary vascular events
      may be a cause of the neurological disease, as opposed to a mere participant
      recruited by a primary neuronal origin of pathology? Whereas some hereditary and
      acquired cerebral angiopathies could be considered a primary cause of
      neurological symptoms of the disease, the epidemiological studies showing a high
      degree of comorbidity among vascular disease and dementias, including Alzheimer's
      disease, as well as migraine and epilepsy, suggested that primary vascular
      pathology may be etiological factor causing neuronal dysfunction or degeneration
      in these diseases. This review focuses on recent hypotheses and evidence,
      suggesting that pathophysiology of the NVU may be initiating trigger for neuronal
      pathology and subsequent neurological manifestations of the disease.

PMID- 22395207
TI  - Biophysical and physiological origins of blood oxygenation level-dependent fMRI
      signals.
AB  - After its discovery in 1990, blood oxygenation level-dependent (BOLD) contrast in
      functional magnetic resonance imaging (fMRI) has been widely used to map brain
      activation in humans and animals. Since fMRI relies on signal changes induced by
      neural activity, its signal source can be complex and is also dependent on
      imaging parameters and techniques. In this review, we identify and describe the
      origins of BOLD fMRI signals, including the topics of (1) effects of spin
      density, volume fraction, inflow, perfusion, and susceptibility as potential
      contributors to BOLD fMRI, (2) intravascular and extravascular contributions to
      conventional gradient-echo and spin-echo BOLD fMRI, (3) spatial specificity of
      hemodynamic-based fMRI related to vascular architecture and intrinsic hemodynamic
      responses, (4) BOLD signal contributions from functional changes in cerebral
      blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of
      O(2) utilization (CMRO(2)), (5) dynamic responses of BOLD, CBF, CMRO(2), and
      arterial and venous CBV, (6) potential sources of initial BOLD dips, poststimulus
      BOLD undershoots, and prolonged negative BOLD fMRI signals, (7) dependence of
      stimulus-evoked BOLD signals on baseline physiology, and (8) basis of resting
      state BOLD fluctuations. These discussions are highly relevant to interpreting
      BOLD fMRI signals as physiological means.

PMID- 22395210
TI  - A nonlinear dynamical theory of cell injury.
AB  - Multifactorial injuries, such as ischemia, trauma, etc., have proven stubbornly
      elusive to clinical therapeutics, in spite of the binary outcome of recovery or
      death. This may be due, in part, to the lack of formal approaches to cell injury.
      We present a minimal system of nonlinear ordinary differential equations
      describing a theory of cell injury dynamics. A mutual antagonism between injury
      driven total damage and total induced stress responses gives rise to attractors
      representing recovery or death. Solving across a range of injury magnitudes
      defines an 'injury course' containing a well-defined tipping point between
      recovery and death. Via the model, therapeutics is the diverting of a system on a
      pro-death trajectory to a pro-survival trajectory on bistable phase planes. The
      model plausibly explains why laboratory-based therapies have tended to fail
      clinically. A survival outcome is easy to achieve when lethal injury is close to
      the tipping point, but becomes progressively difficult as injury magnitudes
      increase, and there is an upper limit to salvageable injuries. The model offers
      novel insights into cell injury that may assist in overcoming barriers that have
      prevented development of clinically effective therapies for multifactorial
      conditions, as exemplified by brain ischemia.

PMID- 22395212
TI  - Dealing with the childhood obesity epidemic: a public health approach.
AB  - Childhood obesity is one of the most pressing public health and medical problems
      in the United States. In the US, prevalence rates of childhood overweight and
      obesity have tripled in the past 30 years and the health implications and related
      medical costs of the disease are already evident. For the first time ever, weight
      related Type 2 diabetes is being diagnosed in youth. Experts suggest that even if
      obesity prevalence remains static in the US, the lifetime risk of Type 2 diabetes
      for children born in 2000 is estimated at 30% for boys and 40% for girls (Narayan
      et al. J Am Med Assoc 290(14): 1884-1890, 2003). Annual hospital-related costs
      associated with treating obese children increased from 35 million dollars in 1979
      to more than 127 million dollars in 1997-1999, based on 2001 dollars (Wang and
      Dietz Pediatrics 109(5): E81-E86, 2002). In addition to financial costs related
      to treating obesity, there are myriad social and personal costs of being an obese
      child and adult. This alarming rise in obesity rates among youth has been
      followed by initiatives by both the medical and public health communities to find
      appropriate and effective treatments as well as ways to prevent obesity. The
      following offers an overview of current trends and initiatives from both sectors
      and concludes with some thoughts on what the future may hold.

PMID- 22395211
TI  - Computerized monitoring of patient-reported speech and swallowing problems in
      head and neck cancer patients in clinical practice.
AB  - PURPOSE: The purpose of this study is to evaluate computerized monitoring of
      speech and swallowing outcomes and its impact on quality of life (QoL) and
      emotional well-being in head and neck cancer patients in an outpatient clinic.
      METHODS: Sixty-seven patients, treated by single or multimodality treatment,
      completed the EORTC QLQ-C30 and QLQ-H&N35 questionnaires and the Hospital Anxiety
      and Depression Scale in an outpatient clinic, using a touch screen computer
      system (OncoQuest), at baseline (at time of diagnosis) and first follow-up (1
      month after end of treatment). RESULTS: Tumor sites included oral cavity (n =
      12), oropharynx (n = 18), hypopharynx (n = 8), and larynx (n = 29). Tumor stage
      included carcinoma in situ (n = 3), stage I (n = 21), stage II (n = 7), stage III
      (n = 15), and IV (n = 21). No speech or swallowing problems at baseline or follow
      up were noted in 23 % (speech) and 41 % (swallowing) of patients. Twenty-one
      percent (speech) and 19 % (swallowing) had problems at baseline and returned to
      normal scores at follow-up, while 16 % (speech) and 19 % (swallowing) had normal
      scores at baseline and developed problems at follow-up. Forty percent (speech)
      and 21 % (swallowing) had persistent problems from baseline to follow-up. At
      baseline, speech problems were significantly related to tumor site and emotional
      distress. At baseline and follow-up, swallowing problems were significantly
      related to QoL and emotional distress. At follow-up, speech problems were
      significantly related to QoL, emotional distress, and swallowing problems.
      CONCLUSIONS: Monitoring speech and swallowing problems through OncoQuest in an
      outpatient clinic is feasible. Many patients report speech and swallowing
      problems, negatively affecting their QoL and emotional well-being.

PMID- 22395213
TI  - Hemophagocytic lymphohistiocytosis can mimic the superior vena cava syndrome.
AB  - We report a case of a 3-year-old boy with hemophagocytic lymphohistiocytosis
      (HLH), with enlarged cervical lymph nodes causing internal jugular vein
      compression, who initially presented a condition similar to the superior vena
      cava syndrome. Laboratory data along with neck node and bone marrow biopsies
      confirmed the HLH. Genetic analysis revealed the patient to be compound
      heterozygous for 2 variations of the perforin gene, c.1620 A>G and c.562C>G. This
      case featuring a rare initial manifestation of HLH that has not been previously
      reported, points to the necessity of considering this disease when symptoms
      similar to superior vena cava syndrome are encountered.

PMID- 22395214
TI  - Childhood acute lymphoblastic leukemia outcome in India:  progress on all fronts.

PMID- 22395215
TI  - A translocation t(5;15)(q15;q11-13) infant case with acute lymphoblastic leukemia
      and literature review: prognosis implications.
AB  - Infant acute lymphoblastic leukemia (ALL) represents poor prognosis despite
      intensive chemotherapy. Rearrangements of chromosome 11q23 are not observed in
      34% of the cases. Infant ALL patients with t(5;15)(p15;q11-13) are rare and
      sporadic. In large series of infant ALL studies, 6 patients have been reported.
      We present a new case of an infant ALL patient with t(5;15)(p15;q11-13), and a
      literature review. Considering the data provided by our case and previous
      reports, we reinforce that this chromosomal abnormality is characteristic of ALL
      patients under 12 months of age sharing break point in 5p15 and 15q11-13 and
      strengthen the existence of an infant ALL subgroup characterized by pre-B L1 ALL,
      CD10-positive, complete remission (100%), and event-free survival (71%), with a
      relatively good prognosis and clearly less severe than the 11q23 rearrangement
      cases. This abnormality can be considered a recurrent abnormality on this
      nosologic group.

PMID- 22395216
TI  - The surgical management of a stage III Wilms tumor presenting with perforated
      appendicitis.
AB  - The majority of the cases of nephroblastoma do not present with abdominal pain.
      We present a patient with an acute surgical abdomen due to perforated
      appendicitis and an incidental abdominal mass. He underwent an urgent
      appendectomy after which tumor specific therapy was successfully initiated.

PMID- 22395217
TI  - Cardiac metastases of Ewing sarcoma detected by 18F-FDG PET/CT.
AB  - Positron emission tomography (PET) is widely used in the diagnostic evaluation
      and staging of different malignant tumors. The role of PET/computed tomographic
      scan in detecting distant metastases in the workup of Ewing sarcoma in children
      or young adults is less well defined. We report a case of a boy affected by a
      metastatic Ewing sarcoma with cardiac asymptomatic metastasis detected by F-FDG
      PET/computed tomography.

PMID- 22395218
TI  - Association of IL-1beta -511 polymorphism with severe veno-occlusive disease in
      pediatric-matched allogeneic hematopoietic stem cell transplantation.
AB  - Single nucleotide polymorphisms (SNPs) of the interleukin 1 (IL-1) family have
      been implicated in acute graft-versus-host disease and mortality postallogeneic
      hematopoietic stem cell transplantation (HSCT) in adults. Hepatic veno-occlusive
      disease (VOD) is a well-known complication of HSCT and can result in an increased
      risk of mortality. In this study, we sought to investigate the association of
      both patient and donor genotypes at the IL-1beta -511 cytidine/thymidine (C/T)
      polymorphic site with hepatic VOD and mortality in an exclusive pediatric cohort
      undergoing matched myeloablative allogeneic HSCT. Donor TT genotype was
      associated with higher cumulative incidence of grade III-IV hepatic VOD at 3
      months after transplantation relative to donor CT and CC genotypes (25+/-13.1% in
      TT, 2.9+/-2.9% in CT, and 3.6+/-3.6% in CC; P=0.024). Neither recipient nor donor
      IL-1beta -511 single nucleotide polymorphisms genotypes were associated with
      mortality or relapse. Our findings suggest that donor, rather than host, genotype
      at the IL-1beta -511 polymorphic site may associate with higher risk for severe
      VOD after matched allogeneic HSCT. Our findings challenge the assumption that
      host factors are exclusively responsible for VOD and suggest a novel role for the
      donor inflammasome pathway in inducing injury and microvascular disease after
      HSCT, which merits further study in a larger cohort analysis.

PMID- 22395219
TI  - FLAG-liposomal doxorubicin (Myocet) regimen for refractory or relapsed acute
      leukemia pediatric patients.
AB  - Despite the success in treating the majority of children with newly diagnosed
      acute leukemia, children with relapsed or refractory disease are an exceptionally
      difficult group of patients to cure. We assessed the combination of fludarabine
      with cytarabine and granulocyte colony-stimulating factor (FLAG) and nonpegylated
      liposomal doxorubicin (Myocet) in children with either acute lymphoblastic
      leukemia (ALL) or acute myelogenous leukemia (AML) refractory to first-line
      therapy or who had relapsed after risk-tailored chemotherapy. We treated 35
      patients with FLAG-Myocet. The median age at treatment was 9 years and 7 months
      (range, 1 to 18 y). The 94% of ALL patients (16/17) and the 61% AML patients
      (11/18) achieved complete remission after FLAG-Myocet. A partial response was
      observed in the 17% of AML patients (3/18). Twenty-eight of 35 (80%) patients
      received hematopoetic stem cell transplantation in remission induced by FLAG
      Myocet regimen. The ALL and AML overall survival at 3 years after FLAG-Myocet is
      33% and 38%, respectively. The probability of ALL and AML event-free survival at
      3 years after FLAG-Myocet is 33% and 40%, respectively. The probability of ALL
      and AML disease-free survival at 3 years after hematopoietic stem cell
      transplantation is 19% and 58%, respectively. Nonhematological toxicity was
      remarkably low, while almost all patients showed severe hematological toxicity.
      FLAG-Myocet is an efficient and a well-tolerated regimen that allows nearly all
      patients to undergo hematopoetic stem cell transplantation. FLAG-Myocet proved to
      be safe in terms of acute cardiac toxicity although particular care must be taken
      to reduce infectious complications due to severe myelosuppression. The promising
      results shown in our study need to be confirmed by larger and possibly randomized
      trials.

PMID- 22395220
TI  - Rare complications after second hematopoietic stem cell transplantation for
      thalassemia major.
AB  - We describe an 11-year-old girl with thalassemia major who underwent a second
      hematopoietic stem cell transplantation from a matched related donor and who
      subsequently developed posttransplant lymphoproliferative disorder complicated by
      severe ascending paralysis resembling Guillian-Barre syndrome. Six months later
      she developed a massive pericardial effusion. She received a multimodal treatment
      for these complications and currently, 18 months after transplantation, she is in
      a good clinical condition, is transfusion independent, with no evidence of graft
      versus-host disease and off all treatment. This case highlights the dilemma
      surrounding second hematopoietic stem cell transplantations in hemoglobinopathies
      and the need for a careful, well informed, and collaborative decision-making
      process by patients, families, and medical professionals.

PMID- 22395221
TI  - Bone health evaluation of children and adolescents with homozygous beta
      thalassemia: implications for practice.
AB  - OBJECTIVE: Bone tissue is adversely affected in patients with homozygous beta
      thalassemia. The aim of this study was to find warning signs of bone loss in
      young patients with beta-thalassemia and allow prompt therapeutic interventions.
      METHODS: Thirty-eight patients were studied, 20 boys and 18 girls, aged 5 to 18
      years (median = 14.13 y), on regular transfusions and chelation treatments. Their
      bone mineral density (BMD) was measured with dual x-ray absorptiometry. The
      recorded parameters were weight, height, bone age (BA), transfusion adequacy
      (mean fetal hemoglobin value), and chelation efficacy (mean ferritin value,
      compliance). Tanner stage was also evaluated: 8 prepubertal subjects (stage 1),
      18 peripubertal subjects (stages 2 and 3), and 12 postpubertal patients (stages 4
      and 5). Blood and urine samples were collected for biochemical analysis. RESULTS:
      Mean BMD z score was -1.56 +/- 1.25. Thirteen patients had normal BMD (z score >
      1), 17 patients had low BMD (z score: -1 up to -2.4), and 8 patients had very low
      BMD (z score <-2.5). Low BMD was observed in patients older than 12 years and was
      associated with short stature (r = 0.33, P = 0.04), delayed BA (r = 0.61, P =
      0.01), and increased bone formation markers. There was no correlation of BMD z
      score with sex, fetal hemoglobin value, ferritin, and compliance. Regarding
      Tanner stage, it was associated strongly with short stature (r = 0.57, P = 0.01),
      ferritin (r = -0.38, P = 0.02), and compliance (r = 0.58, P = 0.01). CONCLUSIONS:
      [corrected] The decline in BMD may start early, even in the well-transfused
      patients. This study targets the young patients who are mostly at the risk for
      bone loss, that is short adolescents with delayed BA. Their prompt recognition in
      everyday practice is important, as they will need close monitoring of their BMD
      and metabolic bone profile. In addition, therapeutic interventions, such as
      adequate calcium intake and sunlight exposure, weight-bearing exercise and, in
      cases of vitamin D insufficiency, proper supplementation could be suggested.

PMID- 22395223
TI  - Salt effects on water/hydrophobic liquid interfaces: a molecular dynamics study.
AB  - We investigate structural and dynamical properties of NaCl and KCl solution/n
      decane interfaces. We find that K(+) and Cl(-) ions localize close to the
      interface and modify the orientations of both first-layer and second-layer water
      molecules in the interfacial region. Na(+) and Cl(-) ions are also localized;
      however, they do not affect the orientation significantly. NaCl salts cause an
      increase of the surface tension and the residence time of interfacial water
      molecules. They also decrease the residence time of interfacial n-decane
      molecules. KCl salt has similar effects, although to a smaller extent. These
      findings may help us to better understand biological interfaces in physiological
      solutions.

PMID- 22395224
TI  - Transcatheter arterial chemoembolization confers survival benefit in patients
      with a spontaneously ruptured hepatocellular carcinoma.
AB  - OBJECTIVE: Spontaneous rupture causing a hemoperitoneum is a life-threatening
      complication of hepatocellular carcinoma (HCC). The aim of this study was to
      document clinical features and prognostic factors in patients with a ruptured
      HCC. METHODS: The medical records of 1412 patients with HCC admitted to a single
      tertiary medical center from January 2000 to August 2010 were reviewed. The
      clinical features, treatment modalities, and outcomes were collected. Univariate
      and multivariate analyses were carried out to analyze the factors affecting
      survival. RESULTS: Thirty-five of 1412 patients diagnosed with a ruptured HCC
      were included. The median survival time was 59 days. Transcatheter arterial
      chemoembolization (TACE) was performed in 24 patients and 11 patients were
      managed conservatively. The 24 patients who received TACE achieved hemostasis
      without complications. The 30-day survival was related to better Child-Pugh
      class, higher hemoglobin level, lower creatinine level, and TACE in patients with
      a ruptured HCC. Multivariate analysis showed that patients who received TACE
      [odds ratio (OR), 0.076; P=0.020] or those with higher hemoglobin level (OR,
      0.626; P=0.011) had a better chance of survival. The 30-day survival rate in a
      patient who received TACE was 83.3%. In the TACE group, the 30-day survival was
      independently associated with a higher hemoglobin level (OR, 0.609; P=0.036).
      CONCLUSION: TACE is a minimally invasive treatment that has a high success rate
      for hemostasis. TACE increased the 30-day survival in patients with a ruptured
      HCC. However, survival rates in patients with lower hemoglobin levels, resulting
      in a large amount of bleeding, remained poor regardless of successful TACE.

PMID- 22395225
TI  - Efficacy of adalimumab rescue therapy in patients with chronic refractory
      pouchitis previously treated with infliximab:  a case series.
AB  - AIM: In refractory pouchitis, infliximab (IFX) has been used as rescue therapy;
      however, there is no clinical evidence for the use of adalimumab (ADA). The aim
      of this study was to report the efficacy of ADA in patients with refractory
      pouchitis previously treated with IFX. METHODS: A retrospective, open-label, case
      series was designed. Patients with chronic refractory pouchitis treated with ADA
      were included. All patients were previously treated with IFX. The short-term and
      mid-term efficacy of ADA was evaluated. RESULTS: Eight patients with chronic
      refractory pouchitis treated with ADA were included. After 8 weeks, 13% of the
      patients achieved remission and 62% showed a clinical response. At week 26, 13%
      achieved remission and 38% showed a clinical response. At week 52, 50% of the
      patients avoided a permanent ileostomy but only 25 achieved remission.
      CONCLUSION: ADA treatment was found to be an alternative for patients with
      chronic refractory pouchitis previously treated with IFX.

PMID- 22395226
TI  - Microfluidic magnetophoretic separations of immunomagnetically labeled rare
      mammalian cells.
AB  - Immunomagnetic isolation and magnetophoresis in microfluidics have emerged as
      viable techniques for the separation, fractionation, and enrichment of rare
      cells. Here we present the development and characterization of a microfluidic
      system that incorporates an angled permanent magnet for the lateral
      magnetophoresis of superparamagnetic beads and labeled cell-bead complexes. A
      numerical model, based on the relevant transport processes, is developed as a
      design tool for the demonstration and prediction of magnetophoretic displacement.
      We employ a dimensionless magnetophoresis parameter to efficiently investigate
      the design space, gain insight into the physics of the system, and compare
      results across the vast spectrum of magnetophoretic microfluidic systems. The
      numerical model and theoretical analysis are experimentally validated by the
      lateral magnetophoretic deflection of superparamagnetic beads and magnetically
      labeled breast adenocarcinoma MCF-7 cells in a microfluidic device that
      incorporates a permanent magnet angled relative to the flow. Through the
      dimensionless magnetophoresis parameter, the transition between regimes of
      magnetophoretic action, from hydrodynamically dominated (magnetic deflection) to
      magnetically dominated (magnetic capture), is experimentally identified. This
      powerful tool and theoretical framework enables efficient device and experiment
      design of biologically relevant systems, taking into account their inherent
      variability and labeling distributions. This analysis identifies the necessary
      beads, magnet configuration (orientation), magnet type (permanent, ferromagnetic,
      electromagnet), flow rate, channel geometry, and buffer to achieve the desired
      level of magnetophoretic deflection or capture.

PMID- 22395227
TI  - Helical phase from blending of chiral block copolymer and homopolymer.
AB  - The phase behavior of the binary blends of polystyrene-b-poly(L-lactide) chiral
      block copolymer (BCP*) and polystyrene homopolymer (HS) is found to be strongly
      dependent on the molecular weight (M(n)) of the HS. A helical phase is formed in
      the blends with low-M(n) HS due to an enhancement of helical steric hindrance.

PMID- 22395228
TI  - Dosimetric quantities in radiological protection and risk assessment.
AB  - Central to the application of the system of protection recommended by the
      International Commission on Radiological Protection (ICRP) are the physical
      quantity, absorbed dose, and the protection quantities, equivalent and effective
      dose. These protection quantities are used to set dose limits, constraints and
      reference levels and to test compliance in the various activities of occupational
      and public exposure. They are also used in the assessment of doses from medical
      procedures. Effective dose in particular has proved to be a very valuable
      quantity that allows the summation of doses from external radiation and internal
      doses from different radionuclides in a single risk-related value. However, while
      it is possible to measure external radiation exposures and estimate internal
      exposures down to very low levels of dose, the associated risks, principally of
      cancer, are much less certain. Equivalent and effective doses are calculated
      using simplifying assumptions to apply to reference workers and members of the
      public for the purpose of control of exposures. Risks to individuals or specific
      population groups should be calculated not using these quantities but using best
      scientific information. The purpose of this note is to provide a short and
      readily accessible account of the purpose of the ICRP dosimetric quantities, how
      they are calculated, how they should be used, and how they relate to risk
      estimation.

PMID- 22395229
TI  - Changing parental behaviour to reduce risky drinking among adolescents: current
      evidence and future directions.
AB  - AIMS: Risky drinking among young people is an issue of public concern globally.
      In Australia and elsewhere, there has been a steady increase in alcohol-related
      harms among young people in recent years. The aims of this study were to review
      the nature of parental supply of alcohol to adolescents aged 13-17 years, explore
      parental social networks as a potential avenue for intervention, and propose
      future directions for research with a view to informing public policy and the
      development of interventions to reduce risky drinking. METHODS: Narrative review.
      RESULTS: While a large literature exists concerning parental influence on
      children's drinking, exploration of the volume of alcohol and context of parental
      supply is lacking. Results from cross-sectional and longitudinal studies on the
      impact of parental factors such as monitoring, rule setting, alcohol supply and
      supervision of drinking present an unclear picture. Consequently, translation of
      research findings into advice for parents is problematic. CONCLUSION: We propose
      that future research seeks to (a) gain a better understanding of the volume and
      contexts of parental supply of alcohol, (b) explore the structure of social
      networks among adolescents and their parents, (c) determine the accuracy of
      parents' perceptions of other parents' behaviours and beliefs, (d) develop an
      analytic approach for quantifying aspects of parental networks and (e) evaluate
      low-intensity parental interventions including web programmes.

PMID- 22395230
TI  - Carbohydrate deficient transferrin in a driver's license regranting program.
AB  - AIMS: Carbohydrate deficient transferrin (CDT) is a common diagnostic marker for
      detecting chronic alcohol abuse. For over 2.5 years, it has been used in traffic
      medicine among subjects applying for driver's license renewal or regranting in
      Belgium. We report on data collected during the program and provide an estimation
      of an applicable cut-off point in forensic situations. Using this cut-off, the
      success of the driver's license regranting program is evaluated. METHODS: CDT was
      assayed at Ghent University Hospital by capillary zone electrophoresis, measured
      on the Capillarys 2TM system, in 3977 subjects applying for driver's license
      regranting. Determination of a cut-off was done by using Bhattacharya statistics
      and by adding a measurement uncertainty interval. The outcome of the program was
      evaluated by monitoring CDT values for 163 subjects during one entire year.
      RESULTS: In 3977 subjects (3481 males and 496 females), CDT values were
      significantly higher in men compared with women, but there is no need for a
      gender-specific cut-off value. Drunk drivers under the age of 30 have
      significantly lower CDT values than older subjects, and a separate cut-off could
      be calculated. A general cut-off of 2.3% CDT was calculated for the entire study
      population. Using this cut-off value for evaluating the outcome of the program
      for 163 subjects, the percentage offenders at the beginning (29%) decreased to 8%
      after 1 year. CONCLUSION: Applying a marker for chronic alcohol abuse such as CDT
      for driver's license renewal or regranting is a powerful tool. Analysis of data
      collected over 2.5 years reveals a favorable outcome of the program and a useful
      cut-off point could be determined.

PMID- 22395231
TI  - Results of stenting for postthrombotic venous obstructive lesions.
AB  - Venous obstructive lesions represent a therapeutic challenge. Postthrombotic
      lesions are the most complex and very prone to rethrombosis. Technical success
      can be achieved in more than 85% of the cases (100% when recanalization with
      thrombolysis is not needed) with a low rate of periprocedural complications and
      no mortality. The overall rate of thrombotic events after stenting is around 5%.
      Patency rates depend on multiple criteria, including the need for thrombolysis
      and the involvement of the common femoral vein and of the inferior vena cava.
      Primary, assisted-primary, and secondary patency rates were 67%, 89%, and 93%,
      respectively, at 6 years in the study by Neglen and 66%, 70%, and 77%,
      respectively, in the intention-to-treat European multicentric study, at 5 and 10
      years. Stenting is a minimally invasive and safe technique with good long-term
      clinical results and patency rates. It represents the method of choice for the
      treatment of postthrombotic iliofemoral venous obstructions.

PMID- 22395232
TI  - Investigation of the electrophilic reactivity of the cytotoxic marine alkaloid
      discorhabdin B.
AB  - The mechanisms of action of the cytotoxic marine pyrroloiminoquinone alkaloids
      the discorhabdins are unknown. We have determined that discorhabdin B acts as an
      electrophile towards biomimetic thiol nucleophiles leading to debrominated
      adducts. In contrast, less potent cytotoxins discorhabdins D and Q failed to
      react, supporting an SAR model of cytotoxicity requiring an orchestrated
      combination of an electrophilic Delta(1) carbon centre and a nucleophilic N-18
      amine for potent activity. The stereospecific nature of nucleophile trapping
      exhibited by both enantiomers of discorhabdin B implies the biogenesis of
      ovothiol A substituted discorhabdins H, H(2), K and K(2) need not be mediated by
      enzymatic processes.

PMID- 22395233
TI  - The role of the tibial slope in sustaining and treating anterior cruciate
      ligament injuries.
AB  - PURPOSE: A steep tibial slope may contribute to anterior cruciate ligament (ACL)
      injuries, a higher degree of instability in the case of ACL insufficiency, and
      recurrent instability after ACL reconstruction. A better understanding of the
      significance of the tibial slope could improve the development of ACL injury
      screening and prevention programmes, might serve as a basis for individually
      adapted rehabilitation programmes after ACL reconstruction and could clarify the
      role of slope-decreasing osteotomies in the treatment of ACL insufficiency. This
      article summarizes and discusses the current published literature on these
      topics. METHODS: A comprehensive review of the MEDLINE database was carried out
      to identify relevant articles using multiple different keywords (e.g. 'tibial
      slope', 'anterior cruciate ligament', 'osteotomy', and 'knee instability'). The
      reference lists of the reviewed articles were searched for additional relevant
      articles. RESULTS: In cadaveric studies, an artificially increased tibial slope
      produced an anterior shift of the tibia relative to the femur. While mathematical
      models additionally demonstrated increased strain in the ACL, cadaveric studies
      have not confirmed these findings. There is some evidence that a steep tibial
      slope represents a risk factor for non-contact ACL injuries. MRI-based studies
      indicate that a steep slope of the lateral tibial plateau might specifically be
      responsible for this injury mechanism. The influence of the tibial slope on
      outcomes after ACL reconstruction and the role of slope-decreasing osteotomies in
      the treatment of ACL insufficiency remain unclear. CONCLUSION: The role of the
      tibial slope in sustaining and treating ACL injuries is not well understood.
      Characterizing the tibial plateau surface with a single slope measurement
      represents an insufficient approximation of its three-dimensionality, and the
      biomechanical impact of the tibial slope likely is more complex than previously
      appreciated. LEVEL OF EVIDENCE: IV.

PMID- 22395234
TI  - Quantitative evaluation of freeze-substitution effects on preservation of nuclear
      antigens during preparation of biological samples for immunoelectron microscopy.
AB  - Using quantitative evaluation of immuno-gold labeling and antigen content, we
      evaluated various automated freeze-substitution protocols used in preparation of
      biological samples for immunoelectron microscopy. Protein extraction from
      cryoimmobilized cells was identified as a critical point during the freeze
      substitution. The loss of antigens (potentially available for subsequent immuno
      gold labeling) was not significantly affected by freezing, while the
      cryosubstitution with an organic solvent caused a significant loss of antigens.
      While addition of water can improve visibility of some cell structures, it
      strengthened the negative effect of cryosubstitution on antigen loss by
      extraction. This was, however, significantly reversed in the presence of 0.5%
      glutaraldehyde in the substitution medium. Furthermore, we showed that the level
      of these changes was antigen-dependent. In conclusion, low concentrations of
      glutaraldehyde can be generally recommended for cryosubstitution rather than the
      use of pure solvent, but the exact conditions need to be elaborated individually
      for certain antigens.

PMID- 22395235
TI  - Effect of TGF-beta on Gli2 expression in HL60 and U937 cell lines.
AB  - The Hedgehog (Hh) signaling pathway is involved in a variety of tumor-related
      diseases, including leukemia. The aim of this study was to determine whether
      there is an interaction between the Hh signaling pathway and transforming growth
      factor-beta (TGF-beta) in the HL60 and U937 cell lines. HL60 and U937 cells were
      treated with TGF-beta, tumor necrosis factor-alpha (TNF-alpha) and specific
      inhibitor of Smad3 (SIS3). The expression of Gli2 was detected by real-time PCR
      and western blotting. The results showed that TGF-beta alone did not affect the
      Gli2 expression in HL60 cells, while it significantly reduced the level of Gli2
      expression in U937 cells. TGF-beta+TNF-alpha reduced the expression of Gli2 in
      HL60 cells and U937 cells. The reduction in the level of Gli2 expression in U937
      cells by TGF-beta+TNF-alpha was greater than that caused by TGF-beta alone. SIS3
      inhibited the effect of TGF-beta. Our results suggest that the effect on Gli2
      expression in HL60 and U937 cells induced by TGF-beta is Smad3-dependent and
      independent of Hh receptor signaling.

PMID- 22395236
TI  - The performance of the Rowland Universal Dementia Assessment Scale (RUDAS) for
      cognitive screening in a geriatric outpatient setting.
AB  - BACKGROUND AND AIMS: Dementia is prevalent in the elderly but it is usually
      unrecognized. The Rowland Universal Dementia Assessment Scale (RUDAS) appears to
      be a good screening tool for dementia detection. The objectives are to validate
      RUDAS-Thai for detecting dementia according to Diagnostic and Statistical Manual
      of Mental Disorders- IV-Text Revised (DSM-IV-TR) criteria in a geriatric
      outpatient setting and to determine its optimal cut point. METHODS: This is a
      cross-sectional study in which the target population is patients from a Geriatric
      and Neurology Outpatient Clinic, Srinagarind Hospital, Khon Kaen University who
      were aged 60 years or above. The content validity and test-retest reliability of
      the RUDAS-Thai were performed initially. It was administered to each participant.
      Then a specialist physician assessed each participant for dementia. RESULTS:
      Eighty-nine (44.5%) subjects had dementia, 89 (44.5%) had normal cognition and 22
      (11%) had mild cognitive impairment. The area under the Receiver operating
      characteristic (ROC) curve was 0.82 (0.75-0.87). The optimal cut point was 24/30;
      it provided sensitivity and specificity of 78.7% and 61.8%, respectively. It was
      not influenced by age and gender but by educational level. CONCLUSIONS: The RUDAS
      Thai is a good screening tool for dementia detection in a geriatric outpatient
      setting. It is portable, short-time consuming, and avoids some limitations of the
      Mini-Mental State Examination (MMSE). However, education does affect the scores.
      The scores of 24 or lower is an optimal cut point for an indication of developing
      dementia.

PMID- 22395237
TI  - Identification of protein interacting partners using tandem affinity
      purification.
AB  - A critical and often limiting step in understanding the function of host and
      viral proteins is the identification of interacting cellular or viral protein
      partners. There are many approaches that allow the identification of interacting
      partners, including the yeast two hybrid system, as well as pull down assays
      using recombinant proteins and immunoprecipitation of endogenous proteins
      followed by mass spectrometry identification(1). Recent studies have highlighted
      the utility of double-affinity tag mediated purification, coupled with two
      specific elution steps in the identification of interacting proteins. This
      approach, termed Tandem Affinity Purification (TAP), was initially used in
      yeast(2,3) but more recently has been adapted to use in mammalian cells(4-8).   
      As proof-of-concept we have established a tandem affinity purification (TAP)
      method using the well-characterized eukaryotic translation initiation factor
      eIF4E(9,10).The cellular translation factor eIF4E is a critical component of the
      cellular eIF4F complex involved in cap-dependent translation initiation(10). The
      TAP tag used in the current study is composed of two Protein G units and a
      streptavidin binding peptide separated by a Tobacco Etch Virus (TEV) protease
      cleavage sequence. The TAP tag used in the current study is composed of two
      Protein G units and a streptavidin binding peptide separated by a Tobacco Etch
      Virus (TEV) protease cleavage sequence(8). To forgo the need for the generation
      of clonal cell lines, we developed a rapid system that relies on the expression
      of the TAP-tagged bait protein from an episomally maintained plasmid based on
      pMEP4 (Invitrogen). Expression of tagged murine eIF4E from this plasmid was
      controlled using the cadmium chloride inducible metallothionein promoter.   
      Lysis of the expressing cells and subsequent affinity purification via binding to
      rabbit IgG agarose, TEV protease cleavage, binding to streptavidin linked agarose
      and subsequent biotin elution identified numerous proteins apparently specific to
      the eIF4E pull-down (when compared to control cell lines expressing the TAP tag
      alone). The identities of the proteins were obtained by excision of the bands
      from 1D SDS-PAGE and subsequent tandem mass spectrometry. The identified
      components included the known eIF4E binding proteins eIF4G and 4EBP-1. In
      addition, other components of the eIF4F complex, of which eIF4E is a component
      were identified, namely eIF4A and Poly-A binding protein. The ability to identify
      not only known direct binding partners as well as secondary interacting proteins,
      further highlights the utility of this approach in the characterization of
      proteins of unknown function.

PMID- 22395238
TI  - Does left ventricular function continue to influence mortality following
      contemporary percutaneous coronary intervention?
AB  - BACKGROUND: Left ventricular (LV) dysfunction was associated with adverse outcome
      after percutaneous coronary intervention (PCI) in the balloon-angioplasty and
      bare-metal stent era. Technological advances have reduced complications after
      PCI. The impact of left ventricular ejection fraction (LVEF) on outcomes in
      current clinical practice is unknown, with commonly used risk stratification
      models not consistently incorporating preprocedural LVEF. METHODS: A total of
      2328 consecutive patients undergoing PCI in a single centre between April 2005
      and July 2009 were analysed. Patients were eligible if LVEF had been categorized
      before PCI as good (LVEF >=50%), moderate (LVEF 30-49%) or poor (LVEF <30%).
      Those in cardiogenic shock were excluded. Mortality data were tracked using the
      UK Office of National statistics database. Logistic regression analysis was used
      to predict the risk of mortality at 30-day and long-term follow-up. RESULTS:
      Overall all-cause mortality was 1.0% at 30 days and 5% at long-term follow-up.
      Kaplan-Meier analysis revealed an early divergence in survival curves according
      to LVEF. Mortality rates stratified by LVEF category were 0.4, 1.3 and 6.3% at 30
      days and 3.3, 5.7 and 12.0% in the long term (2.2+/-1.1 years) (P<0.0001).
      Multiple regression analysis confirmed that impaired LVEF (<=50%) independently
      predicts 30-day [hazard ratio 4.20 (confidence interval 2.50-7.04), P=0.001] and
      long-term all-cause mortality [hazard ratio 1.67 (1.28-2.19), P=0.001].
      CONCLUSION: LV impairment remains a strong predictor of early and late mortality
      after PCI. LV function assessment is integral in risk stratification and patient
      optimization and should be recommended, wherever feasible, before PCI.

PMID- 22395239
TI  - Brain natriuretic peptide in apical ballooning syndrome (Takotsubo/stress
      cardiomyopathy):  comparison with acute myocardial infarction.
AB  - OBJECTIVES: Apical ballooning syndrome (ABS) is a transient cause of ventricular
      dysfunction. The aim of this study was to determine the clinical and hemodynamic
      correlates of brain natriuretic peptide (BNP) levels in ABS and compare the
      biomarker profiles in ABS with acute myocardial infarction controls. METHODS:
      Fifty-seven prospectively diagnosed patients with ABS whose BNP and troponin T
      level measurements were available were included. Fifty patients with ST-elevation
      myocardial infarction (STEMI) and 25 individuals with non-ST-elevation myocardial
      infarction (NSTEMI) were included as matched controls. RESULTS: In the ABS
      cohort, the BNP levels were higher in patients older than 65 years compared with
      younger individuals: 767 (269, 951) versus 340 (131, 904.5), P=0.019. There were
      no significant correlations between BNP levels and hemodynamic parameters such as
      left ventricular ejection fraction and end diastolic pressure. There were no
      correlations between BNP and peak troponin T (r=0.03, P=0.8). BNP levels were
      significantly higher in ABS patients when compared with the STEMI and NSTEMI
      controls. The BNP to peak troponin T ratio was significantly higher in ABS
      compared with the STEMI controls 1089.4 (446.7, 3334.8) versus 97.4 (17.9,
      264.7), P=0.04. CONCLUSION: BNP elevation is almost universal in ABS. Cardiac
      hemodynamic indices do not correlate with BNP levels. The magnitude of BNP
      elevation is higher in ABS compared with STEMI and NSTEMI.

PMID- 22395240
TI  - Safety and efficacy of transradial versus transfemoral percutaneous coronary
      intervention in acute myocardial infarction:  a meta-analysis of randomized
      trials.
AB  - BACKGROUND: The transradial approach has gained increasing popularity for
      elective percutaneous coronary intervention. However, the safety and feasibility
      of transradial coronary intervention (TRI) in acute myocardial infarction (AMI)
      remains uncertain. Hence, a meta-analysis of randomized trials was performed to
      compare outcomes of TRI with transfemoral coronary intervention (TFI) in patients
      with AMI. METHODS: A systematic review of the literature revealed seven
      randomized trials involving 1306 patients. Endpoints extracted were access site
      complications, major adverse cardiovascular events, major bleeding, and
      procedural success. Combined relative risks (RRs) across all studies and 95%
      confidence intervals (CIs) were computed. A two-sided alpha error of less than
      0.05 was considered to be statistically significant. RESULTS: Baseline
      characteristics were similar in both groups. Compared with patients undergoing
      TFI, risk of major adverse cardiovascular events (RR: 0.83, CI: 0.51-1.35;
      P=0.45) and major bleeding (RR: 0.51, CI: 0.20-1.26; P=0.14) was similar in
      patients undergoing TRI. The procedural success was similar with both approaches
      (RR: 0.99, CI: 0.96-1.02; P=0.59). However, incidence of access site
      complications was significantly lower in the TRI group (RR: 0.31, CI: 0.17-0.58;
      P<0.001). CONCLUSION: The meta-analysis suggests that TRI may be superior to TFI
      in reducing access site complications in patients with AMI. However, there is no
      difference in procedural success and major bleeding between the two groups.

PMID- 22395242
TI  - Circulating bacterial membrane vesicles cause sepsis in rats.
AB  - Gram-negative bacteria remain the leading cause of sepsis, a disease that is
      consistently in the top 10 causes of death internationally. Curing bacteremia
      alone does not necessarily end the disease process as other factors may cause
      inflammatory damage. Bacterial outer membrane vesicles (OMVs) are naturally
      produced blebs from the outer membrane of gram-negative bacteria, which contain
      various proteins and lipopolysaccharide (LPS). We hypothesize that these vesicles
      initiate an inflammatory response independent of the parent bacteria. Outer
      membrane vesicles were isolated from cultures of Escherichia coli, and the
      concentration of LPS in the OMVs was measured. Adult male Sprague-Dawley rats
      were separated into five treatment groups: OMV, 2xOMV, LPS, lactated Ringer's,
      and sham. Our findings show that infused OMVs elicit physiological, histological,
      and molecular changes in rats that are consistent with sepsis. Hyperdynamic
      changes in heart rates and mean arterial pressures are observed as well as the
      elevation of the proinflammatory cytokines tumor necrosis factor alpha and
      interleukin 6. Downstream events such as the recruitment of neutrophils into
      tissues due to the presentation of vascular adhesion molecules also occur in OMV
      treated animals. Although soluble LPS elicits stronger responses than did OMVs,
      responses to the latter consistently exceeded those associated with lactated
      Ringer's infusion. These results indicate OMVs, independent of the parent
      bacteria, do initiate an inflammatory response; however, further studies are
      required to better characterize the temporal biomolecular interactions involved.

PMID- 22395243
TI  - Measurement of plasma sTREM-1 in patients with severe sepsis receiving early goal
      directed therapy and evaluation of its usefulness.
AB  - The plasma level of soluble triggering receptor expressed on myeloid cells 1
      (sTREM-1) has been shown to be helpful in identifying critically ill patients
      with infection. However, it remains unknown whether it can be used to predict
      prognosis in patients with severe sepsis. This study investigated whether various
      inflammatory mediators, including sTREM-1, could be used as reliable markers to
      predict the prognosis of patients receiving early goal-directed therapy (EGDT).
      We prospectively enrolled patients 18 years or older with severe sepsis from
      April 2009 to May 2010 at a 2,000-bed university hospital. Patients were eligible
      if the initial resuscitation according to EGDT protocol was immediately performed
      at the emergency department. Plasma sTREM-1, C-reactive protein, and
      procalcitonin concentrations were measured on days 0, 3, 7, and 14. Soluble TREM
      1 concentrations were significantly higher at admission and pre-EGDT in
      nonsurvivors (n = 16) than in survivors (n = 47) (514.1 pg/mL [interquartile
      range, 412.7-1,749.5 pg/mL] vs. 182.4 pg/mL [interquartile range, 54.3-327.0
      pg/mL]; P = 0.001). Procalcitonin and C-reactive protein levels did not
      significantly differ, whereas central venous oxygen saturation and lactate levels
      at admission were significantly different between the two groups. The only sTREM
      1 level remained significantly higher in nonsurvivors until death. On
      multivariate regression analysis, log(sTREM-1) (P = 0.028), central venous oxygen
      saturation (P = 0.022), and Simplified Acute Physiology Score II (P = 0.048)
      values at admission were independently significant. These results suggest that
      plasma sTREM-1 level at admission could be used as a marker to identify patients
      with a poor prognosis despite complete initial resuscitation in severe sepsis.

PMID- 22395244
TI  - Ramifications of C-centering rather than N-centering of the active site FeMo-co
      of the enzyme nitrogenase.
AB  - Nitrogenase catalyses the hydrogenation of N(2) to NH(3), and of CO to
      hydrocarbons. The active site is FeMo-co, an Fe(7)MoS(9) cluster with an atom
      (X(c)) at the centre of the inner trigonal prism of six Fe atoms. Calculations
      extending over almost a decade yielded consensus that this atom was nitrogen. The
      first strong experimental data, reported very recently, indicate that the central
      atom is carbon. This paper evaluates differences between C-centered and N
      centered FeMo-co, and addresses the questions: (a) does the finding of C(c)
      diminish the validity of the many previous theoretical simulations (with N(c)) of
      the reactivity and reactions of FeMo-co? and (b) does the published 21-step
      mechanism for N(2) + 6H -> 2NH(3) need major revision? Accordingly, this paper
      first reports comparative (C(c)/N(c)) calculations of the electronic structure of
      FeMo-co, describing the ground and low-lying electronic states, and the
      distribution of electron spin density and of partial charge. The differences are
      clear, but minor. Then, reaction profiles and structures of intermediates and
      transition states are reported for the C-centered and N-centered versions of the
      four key types of reaction step involved in the overall mechanism: (i) binding of
      N(2), (ii) conformational preparation of H on FeMo-co, (iii) H transfers to N,
      and (iv) N-N breaking. Again the differences are small, and the calculated
      activation energies for the previous complete mechanism appear to be essentially
      transferable to C-centered FeMo-co.

PMID- 22395245
TI  - The influence of body size descriptors on the estimation of kidney function in
      normal weight, overweight, obese, and morbidly obese adults.
AB  - BACKGROUND: Dosing adjustments for patients with impaired kidney function are
      often based on estimated creatinine clearance (eCrCl) because measuring kidney
      function is not always possible for dose adjustment. However, there is no
      consensus on the body size descriptor that should be used in the estimation
      equations. OBJECTIVE: To compare the use of alternative body size descriptors
      (ABSDs) on the performance of kidney function estimation equations compared with
      measured CrCl (mCrCl). METHODS: We combined 2 DATA SOURCES: a Food and Drug
      Administration clinical trial database that includes subjects with body mass
      index (BMI) less than 40 kg/m(2) and published data from those 40 kg/m(2) or
      more. The 3 parent equations (Cockcroft-Gault [CG], Modification of Diet in Renal
      Disease [MDRD], Chronic Kidney Disease-Epidemiology Collaboration [CKDEPI]), and
      14 ABSD-modified equations were compared with mCrCl for accuracy, bias,
      agreement, goodness of fit (R(2)), and prediction error. These equations were
      also compared across mCrCl and BMI strata. RESULTS: Subjects (n = 590) were aged
      19-80 years; 33.9% were female and BMI ranged from 17.2 to 95.6 kg/m(2). Compared
      with mCrCl, the use of total weight in the CG equation yielded low accuracy
      (12.5%) and significant bias (-107 mL/min) in the morbidly obese group. In
      contrast, the use of lean body weights (BMI >=40 kg/m(2)) and total +/- adjusted
      weights (BMI <40 kg/m(2)) with the CG equation yielded higher accuracy, greater
      than or equal to 60.7% across all BMI strata, and was unbiased. Transforming the
      MDRD or CKDEPI equations with body surface area improved accuracy only at mCrCl
      of 30-80 mL/min and increased the overall prediction error. CONCLUSIONS: No
      kidney function equation was consistently accurate and unbiased across weight,
      mCrCl, and estimate ranges. The accuracy and overestimation bias of the CG
      equation in obese subjects was improved through the selective use of total,
      adjusted, and lean body weight by BMI strata.

PMID- 22395246
TI  - Intravesicular cidofovir for the treatment of polyomavirus-associated hemorrhagic
      cystitis.
AB  - OBJECTIVE: To review the literature regarding the use of intravesicular cidofovir
      in the treatment of polyomavirus-associated hemorrhagic cystitis. DATA SOURCES:
      Searches of PubMed were conducted, with key search terms including intravesicular
      cidofovir, polyomavirus, BK virus, JC virus, and hemorrhagic cystitis. Limits
      were set to include human subjects. STUDY SELECTION AND DATA EXTRACTION: All
      articles identified were evaluated, and one was excluded due to being published
      only in the German language. All case studies/case series were included if
      patients received at least 1 dose of intravesicular cidofovir for treatment of
      cystitis. DATA SYNTHESIS: Polyomavirus-associated hemorrhagic cystitis is more
      common in immunocompromised patients, particularly those who have undergone stem
      cell transplantation. Early-onset cystitis is often due to chemotherapy agents,
      while cystitis that develops 10-14 days into therapy is often associated with
      infection with polyomavirus, such as BK virus. There is no standard of therapy
      for polyomavirus-associated cystitis other than hyperhydration and continuous
      bladder irrigation, and many different therapeutic agents have been used in this
      setting, with mixed results. One such agent, intravenous cidofovir, provides
      clinical improvement but carries a risk of renal failure. Intravesicular
      cidofovir has been reported in case reports/series to provide positive
      symptomatic improvement; however, it has not been universally found to decrease
      urine viral load. CONCLUSIONS: At this time, it appears that intravesicular
      cidofovir may be used as an option to provide symptomatic relief in patients with
      polyomavirus-associated hemorrhagic cystitis. However, it is not definitively
      known whether its use significantly decreases urine virus load in these patients.
      Larger clinical trials need to be conducted to fully understand the role of
      intravesicular cidofovir in this setting.

PMID- 22395247
TI  - Prophylaxis and treatment of respiratory syncytial virus in adult
      immunocompromised patients.
AB  - OBJECTIVE: To review the literature regarding current strategies and strategies
      under active development for the prevention and treatment of respiratory
      syncytial virus (RSV) infections in immunocompromised adults. DATA SOURCES: The
      MEDLINE/PubMed, EMBASE, and Cochrane databases were queried from January 1980 to
      December 2011 for articles in English using these associated search terms:
      respiratory syncytial virus, ribavirin, intravenous immunoglobulin, IVIG,
      palivizumab, motavizumab, lung, pneumonia, transplantation, bone marrow, cancer,
      malignancy, and vaccine. STUDY SELECTION AND DATA EXTRACTION: All relevant
      original studies, meta-analyses, systematic reviews, and review articles were
      assessed for inclusion. References from pertinent articles were examined for
      additional content not found during the initial search. DATA SYNTHESIS: RSV in
      the immunocompromised adult can lead to significant morbidity and mortality.
      Treatment of RSV-infected adults is limited to antiviral therapy with ribavirin
      (aerosolized, oral, intravenous) and immunomodulation with intravenous
      immunoglobulins, corticosteroids, and palivizumab. Existing literature is
      predominantly case reports, small trials, and retrospective reviews of patients
      infected with RSV who have undergone lung or hematopoietic stem cell
      transplantation (HSCT). Palivizumab may be a viable option for prophylaxis
      against RSV in high-risk adults. Ribavirin is the most studied treatment option
      and should remain the backbone of multidrug regimens. Of the routes of
      administration, aerosolized ribavirin carries the preponderance of evidence and,
      though challenging, is preferred to limit systemic toxicities in the infected
      patient. Addition of an immunomodulator to ribavirin may provide a survival
      benefit over ribavirin alone; however, this has only been studied in a subset of
      HSCT patients with lower respiratory tract RSV infection. CONCLUSIONS: Research
      most strongly supports the use of aerosolized ribavirin as the treatment strategy
      for immunocompromised adults with RSV. Addition of an immunomodulator may provide
      a survival benefit over ribavirin alone. Strategies and supportive data for the
      prevention of RSV infection in the high-risk adult are critically needed.

PMID- 22395248
TI  - Effectiveness and tolerability of a polymyxin B dosing protocol.

PMID- 22395249
TI  - Impact of clinical pharmacist intervention on diabetes-related outcomes in a
      military treatment facility.
AB  - BACKGROUND: Clinical pharmacist management of patients with diabetes has been
      well justified, but there is a lack of research that evaluates the impact of
      pharmacist-managed diabetes care versus standard medical care on American
      Diabetes Association (ADA) treatment goals other than hemoglobin A(1c) (A1C).
      OBJECTIVE: To evaluate the reduction in A1C, blood pressure, and low-density
      lipoprotein cholesterol (LDL-C) for patients with diabetes whose care was managed
      by a clinical pharmacist and compare these values to those of a cohort of
      patients whose care was managed by primary care providers. The difference in
      percentage of patients attaining ADA treatment goals between the 2 groups was
      also evaluated. METHODS: This retrospective chart review identified 98 diabetic
      patients managed by a clinical pharmacist with at least 2 A1C measurements
      between September 15, 2008, and March 15, 2011. The Military Health System
      Population Health Portal was used to identify a similar group of patients with
      diabetes managed by their primary care provider (N = 90). The Armed Forces Health
      Longitudinal Technology Application was used to collect baseline data and the
      most recent measurements for A1C, blood pressure, LDL-C, and documented
      immunizations. RESULTS: The pharmacist group saw positive improvements in all
      primary end points, including a 1.6% reduction in A1C, a 9-mm Hg and 1.4-mm Hg
      reduction in systolic and diastolic blood pressure, respectively, and a 16.3
      mg/dL reduction in LDL-C. Conversely, the control group had an increase of 0.8%
      in A1C and 1.5 mm Hg in diastolic blood pressure. Reductions in systolic blood
      pressure and LDL-C were much less robust than in the pharmacist group (1.6 mm Hg
      and 5.2 mg/dL, respectively). Overall, patients in the pharmacist group were more
      likely to achieve ADA treatment goals. CONCLUSION: Pharmacist management of
      patients with diabetes significantly reduces A1C and allows more patients to meet
      ADA treatment goals. A clinical pharmacist-run diabetes clinic can provide
      numerous clinical benefits to patients.

PMID- 22395250
TI  - Clinical outcomes with ertapenem as a first-line treatment option of infections
      caused by extended-spectrum beta-lactamase producing gram-negative bacteria.
AB  - BACKGROUND: Infections caused by extended-spectrum beta-lactamase (ESBL)
      producing gram-negative organisms are a growing concern in hospitalized patients.
      Traditionally, these infections can be effectively treated by the carbapenem
      class of drugs. In 2005, our institution initiated a protocol for use of
      ertapenem, a carbapenem, as the first-line treatment option for these infections.
      It is unknown whether ertapenem is associated with similar clinical response and
      microbiologic cure rates as those achieved with group 2 carbapenems (imipenem,
      meropenem, doripenem). OBJECTIVE: To describe clinical response and microbiologic
      cure rates associated with ertapenem as first-line treatment of infections caused
      by ESBL-producing organisms. METHODS: This case series included patients who
      received ertapenem for more than 48 hours to treat a documented infection with a
      positive culture for an ESBL-producing organism. Efficacy was determined by the
      clinical response and microbiologic cure rates achieved with ertapenem. RESULTS:
      Seventy-three patients received ertapenem for a mean (SD) of 10.7 (5.9) days. The
      most common (59%) infection site was urine. The most common causative organisms
      were ESBL-producing Klebsiella pneumoniae (47%) and Escherichia coli (48%).
      Clinical response was observed in 78% of patients. Microbiologic cure was
      achieved in 92% of the evaluable population (n = 50). There were no significant
      differences in clinical or microbiologic cure rates across important subgroups.
      CONCLUSIONS: Patients treated with ertapenem achieved favorable clinical response
      and microbiologic cure rates. Our data suggest that ertapenem can be used as an
      alternative to group 2 carbapenems for the treatment of infections caused by ESBL
      producing gram-negative organisms.

PMID- 22395251
TI  - Proposing a redefinition of pharmaceutical care.
AB  - In many clinical practice settings, individual pharmaceutical care practitioners
      have thousands of patients who may receive their service. However, the
      pharmaceutical care approach provides virtually no guidance regarding how
      patients should be identified or prioritized by practicing pharmacists. We
      believe that pharmacists need to be "officially" accountable to specific patient
      groups at high risk for drug- or disease-induced morbidity within their practice.
      Consequently, the current definition of pharmaceutical care and its associated
      care processes need to be modified to ensure the activities of pharmacists are
      being focused on high-priority patients on a consistent basis.

PMID- 22395252
TI  - Brentuximab vedotin: a new age in the treatment of Hodgkin lymphoma and
      anaplastic large cell lymphoma.
AB  - OBJECTIVE: To review the clinical trial data, pharmacology, pharmacokinetics, and
      adverse effects of brentuximab vedotin. DATA SOURCES: A literature search was
      performed using MEDLINE and PubMed (both 1966-October 2011), as well as the
      American Society of Hematology abstracts (2000-January 2012), using the primary
      search terms brentuximab vedotin, SGN-35, Hodgkin lymphoma (HL), and anaplastic
      large cell lymphoma (ALCL). STUDY SELECTION AND DATA EXTRACTION: Published and
      ongoing clinical studies and abstracts in the English language that detail the
      pharmacology, pharmacokinetics, safety, and clinical efficacy of brentuximab
      vedotin in the treatment of HL and ALCL were included in this review. DATA
      SYNTHESIS: Brentuximab vedotin is an antibody drug conjugate that combines the
      anti-CD30 antibody, cAC10, with the synthetic tubulin disrupting agent monomethyl
      auristatin E. A Phase 1 trial in patients with relapsed and refractory HL or
      systemic ALCL supported a dose of 1.8 mg/kg every 3 weeks. The drug was well
      tolerated, with the majority of adverse reactions being grade 1 or 2 in severity.
      Common toxicities included fatigue, pyrexia, diarrhea, nausea, neutropenia, and
      peripheral neuropathy. Phase 2 studies in the same patient populations
      illustrated objective response rates of 73-86% with an acceptable toxicity
      profile. Based on results of these Phase 2 trials, the Food and Drug
      Administration granted approval of brentuximab vedotin in August 2011 for the
      treatment of relapsed and refractory HL or ALCL. CONCLUSIONS: Phase 1 and 2
      clinical trial data indicate that brentuximab vedotin is efficacious and safe in
      patients with relapsed and refractory CD30-positive lymphomas. This agent is
      being investigated in combination with chemotherapy to further elucidate its role
      in lymphoma therapy.

PMID- 22395254
TI  - Pregabalin for the treatment of generalized anxiety disorder.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of pregabalin in the
      treatment of generalized anxiety disorder (GAD). DATA SOURCES: A search of PubMed
      (1966-December 2011) and International Pharmaceutical Abstracts (1970-December
      2011) was conducted using the MeSH and free-text terms pregabalin, anxiety
      disorders, and anxiety. STUDY SELECTION AND DATA EXTRACTION: All English-language
      articles identified through the search were evaluated for inclusion. Only
      randomized controlled trials involving the use of pregabalin for the treatment of
      GAD were included in the review. DATA SYNTHESIS: Eight published trials were
      identified through the search strategy. Successful treatment of GAD with
      pregabalin versus placebo and active comparators has been reported in clinical
      trials. Pregabalin lowered total Hamilton Rating Scale for Anxiety scores within
      1 week and was effective against both somatic and psychic subcomponents. In 1
      controlled clinical trial, pregabalin was found to be effective in patients aged
      65 years and older. Another trial demonstrated improved relapse rates when
      pregabalin, compared with placebo, was used for up to 6 months. The most commonly
      experienced adverse events were somnolence, dizziness, headache, and dry mouth.
      CONCLUSIONS: Available evidence suggests that pregabalin is effective and well
      tolerated in the treatment of GAD. As somnolence and dizziness are common adverse
      effects, caution should be used in elderly patients. Pregabalin rapidly relieves
      anxiety, a benefit that it may have over many other currently available
      therapeutic options besides benzodiazepines. While not a first-line therapy in
      GAD, pregabalin offers another treatment option in patients who do not respond to
      or who suffer intolerable adverse effects from other agents.

PMID- 22395255
TI  - Effect of medication reconciliation on medication costs after hospital discharge
      in relation to hospital pharmacy labor costs.
AB  - BACKGROUND: Medication reconciliation aims to correct discrepancies in medication
      use between health care settings and to check the quality of pharmacotherapy to
      improve effectiveness and safety. In addition, medication reconciliation might
      also reduce costs. OBJECTIVE: To evaluate the effect of medication reconciliation
      on medication costs after hospital discharge in relation to hospital pharmacy
      labor costs. METHODS: A prospective observational study was performed. Patients
      discharged from the pulmonology department were included. A pharmacy team
      assessed medication errors prevented by medication reconciliation. Interventions
      were classified into 3 categories: correcting hospital formulary-induced
      medication changes (eg, reinstating less costly generic drugs used before
      admission), optimizing pharmacotherapy (eg, discontinuing unnecessary laxative),
      and eliminating discrepancies (eg, restarting omitted preadmission medication).
      Because eliminating discrepancies does not represent real costs to society
      (before hospitalization, the patient was also using the medication), these
      medication costs were not included in the cost calculation. Medication costs at 1
      month and 6 months after hospital discharge and the associated labor costs were
      assessed using descriptive statistics and scenario analyses. For the 6-month
      extrapolation, only medication intended for chronic use was included. RESULTS:
      Two hundred sixty-two patients were included. Correcting hospital formulary
      changes saved ?1.63/patient (exchange rate: EUR 1 = USD 1.3443) in medication
      costs at 1 month after discharge and ?9.79 at 6 months. Optimizing
      pharmacotherapy saved ?20.13/patient in medication costs at 1 month and ?86.86 at
      6 months. The associated labor costs for performing medication reconciliation
      were ?41.04/patient. Medication cost savings from correcting hospital formulary
      induced changes and optimizing of pharmacotherapy (?96.65/patient) outweighed the
      labor costs at 6 months extrapolation by ?55.62/patient (sensitivity analysis
      ?37.25-71.10). CONCLUSIONS: Preventing medication errors through medication
      reconciliation results in higher benefits than the costs related to the net time
      investment.

PMID- 22395256
TI  - Pegloticase: a novel agent for treatment-refractory gout.
AB  - OBJECTIVE: To evaluate efficacy and safety of pegloticase, approved by the Food
      and Drug Administration in September 2010 for treatment of patients with chronic
      treatment-refractory gout. DATA SOURCES: Literature searches were conducted using
      PubMed (1948-January 2012), TOXLINE, International Pharmaceutical Abstracts (1970
      January 2012), and Google Scholar using the terms pegloticase, puricase, PEG
      uricase, gout, uricase, and Krystexxa. Results were limited to English-language
      publications. References from selected articles were reviewed to identify
      additional citations. STUDY SELECTION AND DATA EXTRACTION: Studies evaluating the
      pharmacology, pharmacokinetics, safety, and efficacy of pegloticase for the
      treatment of chronic treatment-refractory gout were included. DATA SYNTHESIS:
      Pegloticase represents a novel intravenous treatment option for patients who have
      chronic gout refractory to other available treatments. Pegloticase is a
      recombinant uricase and achieves therapeutic effects by catalyzing oxidation of
      uric acid to allantoin, resulting in decreased uric acid concentrations. Results
      of published trials demonstrate the ability of pegloticase to maintain uric acid
      concentrations below 7 mg/dL in patients with chronic gout. Data supporting
      reduction of gout flares are limited. Pegloticase is well tolerated but
      associated with gout flares and infusion reactions. Other adverse events include
      nausea, dizziness, and back pain. During Phase 3 trials, 2 patients in the
      pegloticase biweekly group and 1 in the monthly group experienced heart failure
      exacerbation; another patient in the monthly group experienced a nonfatal
      myocardial infarction. Providers should exercise caution before administering
      pegloticase to patients with cardiovascular disease. The cost burden and safety
      profile may limit its use in practice, in addition to limited data available to
      support decreases in patient-centered outcomes (eg, gouty attacks). CONCLUSIONS:
      Pegloticase is an effective option for patients with symptomatic gout for whom
      current uric acid-lowering therapies are ineffective or contraindicated.

PMID- 22395259
TI  - Exposure to airborne particulate matter in Kathmandu Valley, Nepal.
AB  - Kathmandu Valley, Nepal, has severe air pollution, although few studies examine
      air pollution and health in this region. To the best of our knowledge, no
      previous studies in Nepal used time-activity diaries or conducted personal
      monitoring of individuals' exposures. We investigated personal exposure of
      particulate matter (PM) with aerodynamic diameter <=2.5 MUm (PM(2.5)) by
      location, occupation, and proximity to roadways. PM(2.5) monitoring, time
      activity diary, respiratory health questionnaire, and spirometer testing were
      performed from 28 June 2009 to 7 August 2009 for 36 subjects, including traffic
      police (TP), indoor officer workers next to main road (IOWs_NMR) and away from
      main road (IOWs_AMR), in urban area (UA), urban residential area, and semi-UA
      (SUA). TP had the highest exposure of all the occupations (average 51.2 MUg/m(3),
      hourly maximum >500 MUg/m(3)). TP levels were higher at the UA than other
      locations. IOW_NMR levels (averaged 46.9 MUg/m(3)) were higher than those of
      IOW_AMR (26.2 MUg/m(3)). Exposure was generally higher during morning rush hours
      (0800-1100 hours) than evening rush hours (1500-1800 hours) for all occupations
      and areas (78% of days for TP and 84% for urban IOW). PM(2.5) personal exposures
      for each occupation at each location exceeded the World Health Organization
      ambient PM(2.5) guideline (25 MUg/m(3)). Findings suggest potential substantial
      health impacts of air pollution on this region, especially for TP.

PMID- 22395258
TI  - Susceptibility to air pollution effects on mortality in Seoul, Korea: a case
      crossover analysis of individual-level effect modifiers.
AB  - Air pollution's mortality effects may differ by subpopulation; however, few
      studies have investigated this issue in Asia. We investigated susceptibility to
      air pollutants on total, cardiovascular, and respiratory mortality in Seoul,
      Korea for the period 2000-2007. We applied time-stratified case-crossover
      analysis, which allows direct modeling of interaction terms, to estimate
      susceptibility based on sex, age, education, marital status, and occupation. An
      interquartile range increase in pollution was associated with odds ratios of 0.94
      (95% confidence interval, 0.25-1.62), 2.27 (1.03-3.53), 1.94 (0.80-3.09), and
      2.21 (1.00-3.43) for total mortality and 1.95 (0.64-3.27), 4.82 (2.18-7.54), 3.64
      (1.46-5.87), and 4.32 (1.77-6.92) for cardiovascular mortality for PM(10),
      nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), and carbon monoxide (CO),
      respectively. Ozone effect estimates were positive, but not statistically
      significant. Results indicate that some populations are more susceptible than
      others. For total or cardiovascular mortality, associations were higher for
      males, those 65-74 years, and those with no education or manual occupation for
      some pollutants. For example, the odds ratio for SO(2) and cardiovascular
      mortality was 1.19 (1.03-1.37) times higher for those with manual occupations
      than professional occupations. Our findings provide evidence that some
      populations are more susceptible to the effects of air pollution than others,
      which has implications for public policy and risk assessment for susceptible
      subpopulations.

PMID- 22395260
TI  - Atomised intranasal midazolam spray as premedication in pediatric patients:
      comparison between two doses of 0.2 and 0.3 mg/kg.
AB  - PURPOSE: Midazolam premedication administered by the intranasal route is
      noninvasive with good bioavailability. Atomised intranasal midazolam spray
      ensures accurate drug dosage and better patient acceptability, with rapid onset
      of action and virtually complete absorption. METHODS: Sixty pediatric patients
      scheduled for elective surgeries were administered atomised intranasal midazolam.
      Two doses of midazolam, of 0.2 and 0.3 mg/kg, were compared. Children were
      observed for achieving satisfactory sedation and separation scores, and face mask
      acceptance. RESULTS: At 10 and 20 min of nasal administration, 70 and 76% of the
      children, respectively, in the 0.3 mg/kg dose group, while 40 and 63% of the
      children, respectively, in the 0.2 mg/kg group were adequately sedated.
      Similarly, at 10 and 20 min after administration, 66.6 and 73.3% of children,
      respectively, in the 0.3 mg/kg group, and 30 and 60% in the 0.2 mg/kg group were
      easily separated from their parents. With regard to face mask acceptance, 33.3%
      of patients in the 0.3 mg/kg group and 16.6% in the 0.2 mg/kg group accepted the
      mask easily. CONCLUSION: Atomised midazolam at 0.3 mg/kg is safe, and achieves
      faster sedation and better separation scores as compared to 0.2 mg/kg.

PMID- 22395261
TI  - Clinical and economic impact of rapid reporting of bacterial identification and
      antimicrobial susceptibility results of the most frequently processed specimen
      types.
AB  - Inappropriate antibiotic prescriptions are associated with an increase in
      healthcare costs and a decrease in the quality of care. The aim of this study was
      to measure the clinical and economic impact of rapid microbiological reporting on
      the specimens most frequently processed by the Microbiology Laboratory. The
      Vitek(r) 2 system (bioMerieux) was used for identification and susceptibility
      testing. Only hospitalized patients with bacterial infections were included. Two
      groups were established, a historical control group (results available the day
      following the analysis) and an intervention group (results available the same day
      of the analysis). Specimens studied and the median length of time from the
      introduction of the microorganism in the Vitek(r) 2 until microbiological report
      were as follows: wound and abscess (control = 23.5 h, intervention = 9.5 h, p <
      0.001), blood (control = 23.5 h, intervention = 9.2 h, p < 0.001), and urine
      (control = 23.4 h, intervention = 9.3 h, p < 0.001). Outcome parameters were
      hospital stay and mortality rates. Hospital costs were calculated. The mortality
      rates did not differ significantly between the two groups. Faster reporting of
      identification and antimicrobial susceptibility results was associated with a
      significant reduction in hospital stay and in overall costs for those patients
      from whom wound, abscess, and urine specimens were analyzed. However, the
      antimicrobial results of blood culture isolates did not lead to significant
      clinical or financial benefits.

PMID- 22395262
TI  - The optimal aminoglycoside and its dosage for the treatment of severe
      Enterococcus faecalis infection. An experimental study in the rabbit endocarditis
      model.
AB  - Aminoglycosides are recommended for the treatment of Enterococcus faecalis
      infections, especially in severe and bacteremic infection. However, the optimal
      aminoglycoside or the optimal dosage remains uncertain. This study aimed to
      compare the activity of four aminoglycosides against E. faecalis (gentamicin,
      netilmicin, tobramycin, and amikacin) and two dosages of gentamicin. One clinical
      strain of E. faecalis was used to induce aortic endocarditis in the study
      rabbits. Each aminoglycoside was infused daily over 3 days with a computer
      regulated flow simulating human pharmacokinetics of 15 mg/kg/day for amikacin, 6
      mg/kg/day for netilmicin, and 3 mg/kg/day for gentamicin and tobramycin.
      Additionally, two dosages of gentamicin (simulating 3 or 6 mg/kg/day) were
      compared over 1 or 3 days of treatment. The in vivo efficacy was assessed
      according to the bacterial count in vegetations, in comparison with a control
      group. Of the four aminoglycosides tested, only gentamicin and netilmicin showed
      significant antibacterial efficacy after 3 days of treatment. After only 1 day of
      treatment, the high dosage of gentamicin (6 mg/kg/day) was more effective than
      the standard dosage (3 mg/kg/day). Among the tested aminoglycosides, gentamicin
      showed the best efficacy, with the best results after 24 h of treatment for the
      highest dosage.

PMID- 22395263
TI  - Differences in 200-m sprint running performance between outdoor and indoor
      venues.
AB  - Athletes' times in 200-m indoor races are greater than in outdoor races. The
      purpose of this study was to determine which 50-m sections were slower indoors
      than outdoors in 200-m sprint events and by how much. Using 2-dimensional
      photogrammetric techniques, a 50-m split-time analysis was made of the
      performance of 17 men and 16 women, all well-trained athletes, at 4 national
      competitions held over 5 years. The time taken to run the 0- to 50-m section was
      longer indoors than outdoors in women (6.89 +/- 0.12 vs. 6.75 +/- 0.04 seconds; p
      < 0.05) and in men (6.18 +/- 0.10 vs. 6.08 +/- 0.09 seconds; p < 0.05).
      Similarly, both women and men took more time to run the 100- to 150-m section
      indoors (6.03 +/- 0.15 vs. 5.84 +/- 0.06 seconds; p < 0.01, respectively) than
      outdoors (5.26 +/- 0.15 vs. 5.06 +/- 0.07 seconds; p < 0.01, respectively). Both
      sections indoors were run mostly on the curve. However, significant differences
      were not found in the split times for 50-100 and 150-200 m in either sex. In both
      categories, the relative average velocity (RAV), percentage of average velocity
      relative to the maximum velocity reached in the fastest section (50-100 m), was
      about 3% lower indoors than outdoors in 100- to 150-m section. The athletes'
      lower capacity to develop speed indoors could be caused specifically, by the
      curved 0- to 50-m and 100- to 150-m sections of the indoor track. Coaches could
      use these data as reference values there being few published data from high-level
      competitions. The RAV could be used by coaches to compare results among athletes
      of different levels and sexes.

PMID- 22395264
TI  - Impact of neuromuscular fatigue on match exercise intensity and performance in
      elite Australian football.
AB  - This study aimed to quantify the influence of neuromuscular fatigue (NMF) via
      flight time to contraction time ratio (FT:CT) obtained from a countermovement
      jump (CMJ) on the relationships between yo-yo intermittent recovery (level 2)
      test (yo-yo IR2), match exercise intensity (high-intensity running [HIR] m.min(
      1) and Load.min(-1)) and Australian football (AF) performance. Thirty-seven data
      sets were collected from 17 different players across 22 elite AF matches. Each
      data set comprised an athlete's yo-yo IR2 score before the start of the season,
      match exercise intensity via global positioning system and on-field performance
      rated by coaches' votes and number of ball disposals. Each data set was
      categorized as normal (>92% baseline FT:CT, n = 20) or fatigued (<92% baseline
      FT:CT, n = 17) from a single CMJ performed 96 hours after the previous match.
      Moderation-mediation analysis was completed with yo-yo IR2 (independent
      variable), match exercise intensity (mediator), and AF performance (dependent
      variable) with NMF status as the conditional variable. Isolated interactions
      between variables were analyzed by Pearson's correlation and effect size
      statistics. The Yo-yo IR2 score showed an indirect influence on the number of
      ball disposals via HIR m.min(-1) regardless of NMF status (normal FT:CT indirect
      effect = 0.019, p < 0.1, reduced FT:CT indirect effect = 0.022, p < 0.1).
      However, the yo-yo IR2 score only influenced coaches' votes via Load.min(-1) in
      the nonfatigued state (normal: FT:CT indirect effect = 0.007, p <0.1, reduced:
      FT:CT indirect effect = -0.001, p > 0.1). In isolation, NMF status also reduces
      relationships between yo-yo IR2 and load.min(-1), yo-yo IR2 and coaches votes,
      Load.min(-1) and coaches' votes (Deltar > 0.1). Routinely testing yo-yo IR2
      capacity, NMF via FT:CT and monitoring Load.min(-1) in conjunction with HIR
      m.min(-1) as exercise intensity measures in elite AF is recommended.

PMID- 22395265
TI  - An investigation into the effect of a pre-performance strategy on jump
      performance.
AB  - The aim of this study was to explore the effect that different components, making
      up a commonly used pre-performance preparation strategy, have on jump height
      performance. Sixteen male collegiate athletes (age, 21.38 +/- 0.52 years; height,
      1.79 +/- 0.07 m; and body mass, 75.1 +/- 5.26 kg) performed a preparation
      strategy involving a cycle ergometer warm-up, followed by a dynamic stretch
      component, and finishing with heavy back squats. This intervention was repeated
      to test countermovement, squat or drop jump performance after each component of
      the preparation strategy, with electromyographic activity measured during each
      jump test. Significant increases (p < 0.05) in jump height and electromyographic
      activity were noted, with a stepwise increase in performance from pre- to post
      warm-up, increased further by the dynamic stretch component and again increased
      after the back squat. It was also noted that the increases in performance,
      attributed to the stretch and lift components, were significantly greater (p <
      0.05) than the increases in jump height associated with the active warm-up. It
      seems likely that the initial active warm-up raised core temperature, helping to
      increase the jump performance. The specific movements employed in the stretch and
      lift interventions seemed to potentiate the agonistic muscles involved in
      jumping, shown by increases in electromyographic activity in the prime movers for
      the jumps explored. This could be an example of postactivation potentiation,
      where muscles are primed to increase performance beyond changes linked to an
      active warm-up.

PMID- 22395266
TI  - The effect of variety on physical activity:  a cross-sectional study.
AB  - It has been repeatedly demonstrated that increasing the variety of available food
      and purchasing options reliably increases eating and consumer spending behavior,
      respectively. However, the potential probehavioral effect of increasing the
      variety of exercise equipment options on the amount of exercise individuals
      perform is very limited. The purpose of this investigation was to compare the
      amount, enjoyment (liking), and effort perception of resistance training exercise
      vs. sedentary alternatives during a high-variety (HV) resistance-exercise
      equipment condition (10 choices) vs. a low-variety (LV) equipment condition (2
      choices). During each condition (HV) and (LV), children (8-12 years), young
      adults (18-26 years), and older adults (>=60 years) had free-choice access to
      both resistance-exercise equipment and sedentary activities for a total of 20
      minutes. The amount of time allocated to resistance exercise, the total number of
      repetitions performed, and session liking were measured during each condition.
      The participants significantly (p <= 0.05 for all) increased: repetitions
      performed (126.4 +/- 71.7 vs. 88.0 +/- 48.8), the amount of time allocated for
      exercise (14.3 +/- 6.3 vs. 12.1 +/- 6.5 minutes) and liking (8.1 +/- 1.5 vs. 7.1
      +/- 2.1 cm) during the HV condition relative to the LV condition. The rating of
      perceived exertion was not significantly (p = 0.13) different from HV (4.2 +/-
      2.4) to LV (3.8 +/- 2.3). Increasing the variety of exercise equipment available
      to children, young and older adults increased their exercise participation and
      enjoyment of that exercise without altering their perceived exertion. The
      practical application from this research is that increasing the variety of
      exercise equipment available to one's clients may increase their exercise
      adherence.

PMID- 22395267
TI  - Responsiveness of muscle tone characteristics to progressive force production.
AB  - It is possible to measure muscle tone reliably, quickly and objectively using
      tonometers although they are not yet widely used. In clinical practice, it may be
      helpful if clinicians could assess the degree of contraction in different parts
      of a muscle without having to perform time-consuming electromyography
      measurements. The purpose of this study was to evaluate the responsiveness of
      different muscle tone characteristics to progressively increased contraction
      force of quadriceps muscle. Twenty healthy subjects (mean age 39.9 years, 50%
      women) volunteered. Using 2 different tonometers various muscle viscoelastic
      properties were measured. The frequency (hertz), logarithmic decrement, and
      stiffness (newtons per meter) of damped mechanical oscillation of the muscle
      tissue and tissue compliance (millijoules) were registered from rectus femoris
      muscle at rest and 20, 40, 60, 80% of maximal voluntary contraction determined
      using dynamometry. All the values changed linearly with increasing force level.
      Compliance, oscillation stiffness, and frequency parameters showed large effect
      sizes (ESs >= 0.8). The standardized respoknse mean for compliance was 5.3 (4.8
      5.7) mJ, for oscillation stiffness 1.8 (1.3-2.2) N.m(-1), frequency 1.1 (0.6-1.5)
      Hz, and decrement -0.6 (-1.0 to -0.2). The results indicate that the compliance
      and oscillation stiffness parameters showed the highest responsiveness and can
      thus best detect changes in muscle contraction state. The additional value of
      using tonometers to measure these properties in clinical practice should be
      investigated further.

PMID- 22395268
TI  - Physical and physiological demands of field and assistant soccer referees during
      America's cup.
AB  - The aim of this study was to examine the physical and physiological demands of
      top-class soccer field (FR; n = 7) and assistant (AR; n = 7) referees during
      America's Cup. The FR and AR were equipped with a global positioning system (GPS)
      and a heart rate (HR) monitor for the recording of displacements and
      cardiovascular stress, respectively, every 5 and 15 minutes, halves, and entire
      match. High-intensity accelerations (ACs) and a new index of performance
      efficiency (Effindex) were also examined during each match. The FR completed
      longer distances for all walking and running activities and exhibited a greater
      match HR compared with the AR. The FR exhibited a significant reduction in the
      mean number of ACs during the second half (40 vs. 28), with a significantly worse
      Effindex at the end of both halves for FR and at the end of the second half for
      AR. A significant correlation between FR and AR for the number (r = 0.336; p =
      0.03) and distance (r = 0.367; p = 0.017) of ACs performed each 5-minute period
      indicated a synchronization of officials' activities. In conclusion, top-class
      American FR and AR exhibited similar physical demands as previously reported by
      their European counterparts during international tournaments. The high number of
      AC observed, the effect of fatigue on these actions over the match, and the AC's
      synchronization between FR and AR suggest that ACs should be considered for the
      preparation of referees and team sport athletes. The Effindex may provide an
      important tool for the evaluation of referees' and players' performance that
      requires further investigation.

PMID- 22395269
TI  - Effect of match importance on salivary cortisol and immunoglobulin A responses in
      elite young volleyball players.
AB  - The purpose of this study was to compare the session ratings of perceived
      exertion (Session-RPE) responses and the salivary cortisol (sC) and
      immunoglobulin A (SIgA) levels between a regular season match (RM) and the final
      championship match (FM) in elite male volleyball players against the same
      opponent team. Higher importance was assumed for FM because this match would
      define the championship team. Session-RPE was obtained after 30 minutes of each
      match using the CR-10 scale. Saliva samples were collected before and after each
      match and during a rest day (baseline) at the same period of the matches. The
      SIgA and sC concentrations were measured by enzyme-linked immunosorbent assay.
      Greater Session-RPE was observed for FM as compared with RM (p < 0.01). The
      analysis of variance showed greater sC concentrations to FM as compared with RM
      for both prevalues and postvalues and compared with baseline (p < 0.05).
      Significant lower SIgA prevalues were noted for FM. In conclusion, the results
      showed that match intensity, cortisol concentration, and SIgA prelevel were
      affected by the match importance. These results indicate that monitoring session
      RPE, sC, and SIgA responses, in conjunction, during training and competition,
      would provide valuable informations regarding how athletes cope with sports
      induced stress. This study provided knowledge about the effect of match
      importance on salivary markers related to stress that may help coaches to avoid
      excessive training loads reducing the likelihood to decrements on mucosal
      immunity and its consequent risk to upper respiratory tract infections, which in
      turn might affect the performance.

PMID- 22395270
TI  - The contribution of step characteristics to sprint running performance in high
      level male and female athletes.
AB  - We investigated the interaction between step length and step rate and its effect
      on sprint performance in male and female sprinters during initial acceleration
      (IA) (0-10 m), transition phase (TP) (10-30 m), and at maximal speed (MS). Ten
      high-level male and female sprinters ran 2 all-out 60-m sprints. Force-time
      characteristics of start action were recorded by means of instrumented starting
      blocks. Running speed and acceleration were recorded using a laser system (ULS),
      whereas step length and step rate were measured for each step (Optojump). Step
      length was normalized for leg length. Explosive strength of the lower limb
      muscles was quantified using vertical jump performance, showing a 24.6% higher
      score in men compared with women. During the 3 phases of sprinting, step rate
      remained constant and did not differ significantly between men (IA: 4.37 +/- 0.21
      Hz, TP: 4.47 +/- 0.25 Hz, MS: 4.43 +/- 0.18 Hz) and women (IA: 4.23 +/- 0.18 Hz,
      TP: 4.34 +/- 0.18 Hz, MS: 4.28 +/- 0.17 Hz). The data analysis indicates that
      step characteristics interact differently in men and women across phases. Men do
      not take full advantage of their higher explosive strength to develop step length
      and speed during IA, because normalized step length differed only slightly (
      4.09%) between men (1.70 +/- 0.21) and women (1.66 +/- 0.13). However, men
      outscored women clearly in acceleration (+34.5%) during the TP because they were
      capable of developing higher step lengths (2.04 +/- 0.12 m in men vs. 1.85 +/-
      0.07 m in women), even when normalized for leg length (2.65 +/- 0.12 in men vs.
      2.47 +/- 0.22 in women). At MS, it was concluded that men and women pursue an
      optimal balance between step rate and step length because a high negative
      correlation was found in both sexes (r = -0.94 and r = -0.77). Therefore,
      training approach needs to be customized to gender-related differences in step
      length-rate interaction.

PMID- 22395272
TI  - The effect of nonleading foot placement on power and velocity in the fencing
      lunge.
AB  - The fencing lunge is a sport-specific movement, which helps the fencer score
      quickly and accurately. The fencing lunge is executed from a stable guard
      position, with the toes of the leading foot pointing directly toward the
      opponent. As a result of coach or fencer preference, however, the angle of the
      nonleading foot may vary greatly among fencers, from acute (nonleading foot
      facing forward) to obtuse (nonleading foot facing slightly backward). Studies in
      other sports suggest that foot placement may affect the efficient use of leg
      muscles and influence the power produced. Twenty-five experienced fencers from
      the U.S. Air Force Academy fencing team executed lunges from 3 specific angles of
      nonleading foot placement and from the natural stance. Foot placements were
      measured as the angle of the nonleading foot from the line of the leading foot
      and were delimited to an acute angle (45 degrees ), a perpendicular angle (90
      degrees ), and an obtuse angle (135 degrees ). The angle of natural stance was
      also determined for each participant. Velocity and power were measured with a
      TENDO Weightlifting Analyzer, and the data were analyzed with repeated measures
      analysis of variance. Two statistical groups were considered, one containing all
      participants (N = 25) and a second group of participants with a natural forward
      deviated stance (n = 15). Significant differences appeared between the nonleading
      foot placements in peak power (p < 0.001), average power (p < 0.001), peak
      velocity (p < 0.001), and average velocity (p < 0.001) in both groups. Pairwise t
      test results indicated that, for both statistical groups, a perpendicular
      placement of the feet produced the greatest power and velocity during lunging.

PMID- 22395273
TI  - A comparison of assisted and unassisted proprioceptive neuromuscular facilitation
      techniques and static stretching.
AB  - A comparison of assisted and unassisted proprioceptive neuromuscular facilitation
      techniques and static stretching. J Strength Cond Res 26(5): 1238-1244, 2012
      Proprioceptive neuromuscular facilitation (PNF) stretching often requires a
      partner. Straps are available allowing an individual to perform PNF stretching
      alone. It is not known if a strap provides similar improvements in the range of
      motion (ROM) as partner-assisted PNF or static stretching. The purpose of this
      study was to compare assisted and unassisted (with a strap) PNF stretching and
      static stretching. Hip joint ROM, reaction time (RT), and movement time (MT) were
      measured prestretching and poststretching. Thirteen recreationally active adults
      participated in this study. The participants were subjected to 5 different
      stretch interventions in a random order on separate days. Stretch conditions
      included unassisted PNF stretching using (a) isometric, (b) concentric, and (c)
      eccentric contractions with a stretch strap, (d) partner-assisted isometric PNF,
      and (e) static stretching. The RT, MT, dynamic, active, passive hip flexion
      angle, and angular velocity with dynamic hip flexion were measured before and
      after the intervention. The ROM improved (p < 0.05) 2.6, 2.7, and 5.4%,
      respectively, with dynamic, active static, and passive static ROM, but there was
      no significant difference between the stretching protocols. There was a main
      effect for time (p < 0.05) with all stretching conditions negatively impacting
      dynamic angular velocity (9.2%). Although there was no significant effect on RT,
      MT showed a negative main effect for time (p < 0.05) slowing 3.4%. In conclusion,
      it was found that all 3 forms of active stretching provided similar improvements
      in the ROM and poststretching performance decrements in MT and angular velocity.
      Thus, individuals can implement PNF stretching techniques with a partner or alone
      with a strap to improve ROM, but athletes should not use these techniques before
      important competitions or training because of the impairment of limb velocity and
      MT.

PMID- 22395274
TI  - Comparison of kettlebell swings and treadmill running at equivalent rating of
      perceived exertion values.
AB  - The purpose of this study was to compare metabolic demand of a kettlebell (KB)
      swing routine with treadmill (TM) running at equivalent rating of perceived
      exertion (RPE). Thirteen subjects (11 male, 2 female, age = 21.4 +/- 2.1 years,
      weight = 73.0 +/- 9.2 kg) completed a 10-minute KB swing routine consisting of 35
      second swing intervals followed by 25-second rest intervals. Men used a 16-kg KB,
      and women used an 8-kg KB. After 48 hours of rest, the subjects completed a 10
      minute TM run at equivalent RPEs as measured during the swing workout. Metabolic
      data were monitored each minute during each exercise using an automated cart,
      with the final 7 minutes used for analysis. The RPE and heart rate (HR) recorded
      at minutes 5, 7, 9, and 10 increased by 2-3 and 7-9%, respectively, for each
      exercise, producing a significantly increasing pattern but no significant
      difference between exercises. Average HR and RPE were not significantly different
      between KB and TM and averaged 90 and 89%, respectively, of age-predicted HRmax.
      Oxygen consumption, METS, pulmonary ventilation, and calorie expenditure were
      significantly higher for TM (25-39%) than for KB. Respiratory exchange ratio (TM
      = 0.94 +/- 0.04, KB = 0.95 +/- 0.05) and respiratory rate (TM = 38 +/- 7, KB = 36
      +/- 4 b.min) were not significantly different between the exercises at any time
      point. During TM and KB exercises matched for RPE, the subjects are likely to
      have higher oxygen consumption, work at a higher MET level, and burn more
      kilocalories per minute during TM running than during KB swings. However,
      according to the American College of Sports Medicine standards, this KB drill
      could provide sufficient exercise stress to produce gains in aerobic capacity.

PMID- 22395275
TI  - Relationship of off-ice and on-ice performance measures in high school male
      hockey players.
AB  - The purpose of this study was to examine the relationship of off-ice performance
      measures with on-ice turning, crossover, and forward skating performance in high
      school male hockey players. Thirty-eight players aged 15-18 (mean age +/- SD:
      16.4 +/- 1.1 years; height: 177.9 +/- 6.8 cm; weight: 72.5 +/- 8.9 kg)
      participated in this study. On-ice tests included a forward sprint, short radius
      turns, and crossover turns. Off-ice tests included a 40-yd sprint, vertical
      jumps, horizontal jumps, and a dynamic balance test using a Y balance testing
      device. Five off-ice variables correlated with all on-ice performance measures.
      These variables included the 40-yd sprint, lateral bound right to left limb,
      double limb horizontal hop, balance on right in posterolateral direction, and
      composite balance performance on the right. Hierachical regression demonstrated
      that off-ice sprint time was most predictive of on-ice skating performance,
      accounting for 65.4% of the variability in forward skate time, 45.0% of the
      variability in left short radius time, 21.8% of the variance in right short
      radius time, 36.2% of the variance in left crossover time, and 30.8% of the
      variability in right crossover time. When using off-ice tests to evaluate hockey
      players, the 40-yd sprint is the best predictor of skating performance. Based on
      our regression equation, for every 1-second difference in the 40-yd sprint time,
      there will be approximately a 0.6-second difference in the 34.5-m on-ice sprint.
      The 40-yd sprint predicts forward skating performance and to a lesser degree; it
      also predicts crossover and tuning performance.

PMID- 22395277
TI  - Hormone therapy and maximal eccentric exercise alters myostatin-related gene
      expression in postmenopausal women.
AB  - We sought to evaluate baseline mRNA values and changes in gene expression of
      myostatin-related factors in postmenopausal women taking hormone therapy (HT) and
      not taking HT after eccentric exercise. Fourteen postmenopausal women
      participated including 6 controls not using HT (59 +/- 4 years, 63 +/- 17 kg) and
      8 women using HT (59 +/- 4 years, 89 +/- 24 kg). The participants performed 10
      sets of 10 maximal eccentric repetitions of single-leg extension on a
      dynamometer. Muscle biopsies from the vastus lateralis were obtained from the
      exercised leg at baseline and 4 hours after the exercise bout. Gene expression
      was determined using reverse transcriptase polymerase chain reaction for
      myostatin, activin receptor IIb (ActRIIb), follistatin, follistatin-related gene
      (FLRG), follistatin-like-3 (FSTL3), and GDF serum-associated protein-1 (GASP-1).
      In response to the exercise bout, myostatin and ActRIIb significantly decreased
      (p < 0.05), and follistatin, FLRG, FSTL3, and GASP-1 significantly increased in
      both groups (p < 0.05). Significantly greater changes in gene expression of all
      genes occurred in the HT group than in the control group after the acute
      eccentric exercise bout (p < 0.05). These data suggest that postmenopausal women
      using HT express greater myostatin-related gene expression, which may reflect a
      mechanism by which estrogen influences the preservation of muscle mass. Further,
      postmenopausal women using HT experienced a profoundly greater myostatin-related
      response to maximal eccentric exercise.

PMID- 22395278
TI  - Relationship between reactive strength variables in horizontal and vertical drop
      jumps.
AB  - The aim of this study was to investigate the relationship between reactive
      strength in a vertical and a horizontal drop jump (DJ). Subjects (n = 28) with
      previous jump training experience, performed 6 vertical DJs and 6 horizontal DJs
      from a 0.4-m box. Contact time, height jumped, distance jumped, and reactive
      strength index (RSI) were calculated and analyzed. Typical error measurements
      (TEMCV%) and intraclass correlations (ICCs) were used to assess the intrasubject
      reliability. Relationships between jumps and within jumps of the aforementioned
      variables were assessed using ICCs. The ICC (r > 0.789) and the TEMCV% (<10%)
      indicated good reliability for both vertical and horizontal DJs across each
      variable. Contact time showed no relationship between jumps (r = 0.222) and had
      no effect on the vertical DJ height (r = 0.152) or horizontal DJ distance (r =
      0.261). The RSI correlation (r = 0.533) indicated a large relationship between
      reactive ability in the horizontal DJ and the vertical DJ. Contact times were
      significantly lower in vertical DJs compared with horizontal DJs (p < 0.0001).
      This study indicated that horizontal DJs are reliable and may be better used to
      train reactive movements that do not require brief contact times.

PMID- 22395279
TI  - Assessing explosive power production using the backward overhead shot throw and
      the effects of morning resistance exercise on afternoon performance.
AB  - The purpose of this study was to determine if performing a morning total-body
      resistance exercise workout affects explosive power in an afternoon session. The
      secondary goal was to assess the usefulness of the backward overhead shot throw
      (BOST) as a measure of explosive power in experienced thrower in the sport of
      athletics. Throwers (N = 14) performed 1 control and 1 experimental trial on
      separate days. The control consisted of BOST and a vertical jump (VJ) testing
      performed in the afternoon. For the experimental trial, the participants reported
      for a short resistance training session in the morning then repeating the BOST
      and VJ testing 4-6 hours later. The BOST distance (meters) and VJ peak power
      (watts) were correlated in both trials (r ~ 0.64, p < 0.05). The BOST distance
      improved in experimental trial over control (p < 0.05), but VJ power failed to
      improve. The results indicate that a morning resistance exercise bout can improve
      competitive throwing performance later on the same day. The results also suggest
      that BOST may be a useful performance testing tool for throwers in the sports of
      athletics.

PMID- 22395280
TI  - Influence of compressive gear on powerlifting performance:  role of blood flow
      restriction training.
AB  - This study investigated the effects of powerlifting gear on training volume and
      performance, defined by the squat, bench press, and deadlift. Eighteen
      powerlifters (18-26 years) were randomized into either a group that trained and
      competed using compressive gear (CG) or without the gear (NON). Training volume,
      volume progression, and powerlifting performance were assessed before and after
      10 weeks of training. Training volume increased in the first 4 weeks for both
      groups. Volume lifted for squat and the totals were greater in the CG. There was
      an increase in squat (19.05 +/- 30.97 lb, p = 0.02), deadlift (19.05 +/- 21.17
      lb, p = 0.001), and the total score (44.00 +/- 60.44 lb, p = 0.005) for both the
      groups. The improvements in squat (CG = 33.85 vs. NON = 5.74, p = 0.07) and
      totals (CG = 66.59 vs. NON = 23.67, p = 0.15) were greater in the CG. Both groups
      showed a significant and similar increase in the Wilks scores (+13.54 points, p =
      0.03). There was a trend toward greater volume progression in those wearing CG
      during the initial stages of training. Both the groups significantly improved
      performance for the squat, and deadlift, and had higher totals, and Wilks scores,
      indicating significant strength gains. The greater magnitude of improvements in
      the squat and totals for the CG lifters suggests an ergogenic potential of
      training with powerlifting gear.

PMID- 22395281
TI  - Effects of proprioceptive neuromuscular facilitation stretching and static
      stretching on maximal voluntary contraction.
AB  - This study was undertaken to investigate and compare the effects of
      proprioceptive neuromuscular facilitation (PNF) stretching and static stretching
      on maximal voluntary contraction (MVC). Thirteen male university students (age,
      20 +/- 1 years; height, 172.2 +/- 4.6 cm; weight, 68.4 +/- 6.7 kg; mean +/- SD)
      completed 3 different conditions on 3 nonconsecutive days in randomized order:
      static stretching (SS), PNF stretching (PNF), and no stretching (control, CON).
      Each condition consisted of a 5-minute rest accompanied by one of the following
      activities: (a) control, (b) SS, or (c) PNF stretching. The hip flexion range of
      motion (ROM) was evaluated immediately before and after the activity. The MVC of
      knee flexion was then measured. Surface electromyography was recorded from the
      biceps femoris and vastus lateralis muscles during MVC tests and stretching.
      Although increases in ROM were significantly greater after PNF than after SS (p <
      0.01), the decreases in MVC were similar between the 2 treatments. These results
      suggest that, although PNF stretching increases ROM more than SS, PNF stretching
      and SS is detrimental to isometric maximal strength.

PMID- 22395282
TI  - Estimation of internal radiation dose from both immediate releases and continued
      exposures to contaminated materials.
AB  - A brief description is provided of the basic concepts related to 'internal dose'
      and how it differs from doses that result from radioactive materials and direct
      radiation outside of the body. The principles of radiation dose reconstruction,
      as applied to both internal and external doses, are discussed on the basis of a
      recent publication prepared by the US National Council on Radiation Protection
      and Measurements. Finally, ideas are introduced related to residual radioactive
      contamination in the environment that has resulted from the releases from damaged
      reactors and also to the management of wastes that may be generated in both
      regional cleanup and decommissioning of the Fukushima nuclear power plant.

PMID- 22395283
TI  - Involvement of DNA binding domain in the cellular stability and importin affinity
      of NF-kappaB component RelB.
AB  - NF-kappaB is a transcription factor for the immune activation and tissue
      stability, but excess activation of NF-kappaB often causes inflammation and
      cancer. An NF-kappaB component RelB is involved in B-cell maturation and
      autoimmunity. In the present research we studied the role of the RelB DNA binding
      domain on cellular stability and importin affinity. We prepared a RelB protein
      mutated at Arg141 to Ala and Tyr142 to Ala (AA mutant) having no DNA binding
      activity. The stability of this mutant protein was greatly reduced compared with
      that of the wild-type protein. We also constructed a nuclear localization signal
      inactivated mutant of RelB, and found that this mutant was also unstable in the
      cells. Thus, RelB destabilization was caused by the loss of DNA binding possibly
      because of the change in cellular localization. The mutation also decreased the
      affinity to importin-alpha5 decreasing the nuclear localization. Our newly
      discovered NF-kappaB inhibitor (-)-DHMEQ binds to a specific Cys residue in RelB
      to inhibit DNA binding and also decreased the stability and importin affinity.
      These findings would indicate that the DNA binding activity of this transcription
      factor is a crucial for its stability and intracellular localization.

PMID- 22395285
TI  - High selectivity production of propylene from 2-butene: non-degenerate pathways
      to convert symmetric olefins via olefin metathesis.
AB  - The first example of propylene production from 2-butene in promising yield is
      described by reacting trans-2-butene over tungsten hydrides precursor W
      H/Al(2)O(3) at 150  degrees C and different pressures in a continuous flow
      reactor. The tungsten carbene-hydride active site operates as a "bi-functional
      catalyst" through the disfavoured 2-butene isomerisation on W-hydride and 2
      butenes/1-butene cross-metathesis on W-carbene.

PMID- 22395286
TI  - The relationship between atrophy of the medial temporal area and daily activities
      in older adults with mild cognitive impairment.
AB  - BACKGROUND AND AIMS: Many studies have suggested that social network, leisure
      activity, and physical activity can have protective effects against dementia and
      Alzheimer's disease. However, previous studies have not examined the relationship
      between daily activities and brain atrophy in older adults. This study aimed to
      explore what kind of daily activities were associated with atrophy of the medial
      temporal area including the entorhinal cortex (MTA-ERC) in older adults. METHODS:
      In total, 122 older adults (aged 65 and over) with subjective memory complaints
      or a Clinical Dementia Rating of 0.5 underwent magnetic resonance imaging, and
      MTA-ERC atrophy was assessed by the voxel- based morphometry method. Based on
      magnetic resonance imaging data, the subjects were divided into atrophy and non
      atrophy groups. Daily activities were assessed using a 20-item questionnaire
      (e.g., instrumental activities of daily living, social activities), and we
      compared activity participation between the groups. RESULTS: The atrophy group
      (n=37) showed significantly lower participation in 4 out of 20 activity items
      (cleaning, intellectual activity, culture lessons, and using a personal computer)
      than the non-atrophy group (n=85). Summed scores of these 4 items (range from 0
      to 4) were significantly associated with MTA-ERC atrophy even after adjustment
      for age, sex, education status, and Mini-Mental State Examination score.
      CONCLUSIONS: In conclusion, MTAERC atrophy was associated with cognitive
      activities or household-related activities requiring planning.

PMID- 22395284
TI  - Evaluation of muscle fatigue of wheelchair basketball players with spinal cord
      injury using recurrence quantification analysis of surface EMG.
AB  - Wheelchair basketball is the most popular exercise activity among individuals
      with spinal cord injury (SCI). The purpose of this study was to investigate
      muscular endurance and fatigue in wheelchair basketball athletes with SCI using
      surface electromyography (SEMG) and maximal torque values. SEMG characteristics
      of 10 wheelchair basketball players (WBP) were compared to 13 able-bodied
      basketball players and 12 sedentary able-bodied subjects. Participants performed
      sustained isometric elbow flexion at 50% maximal voluntary contraction until
      exhaustion. Elbow flexion torque and SEMG signals were recorded from three elbow
      flexor muscles: biceps brachii longus, biceps brachii brevis and brachioradialis.
      SEMG signals were clustered into 0.5-s epochs with 50% overlap. Root mean square
      (RMS) and median frequency (MDF) of SEMG signals were calculated for each muscle
      and epoch as traditional fatigue monitoring. Recurrence quantification analysis
      was used to extract the percentage of determinism (%DET) of SEMG signals. The
      slope of the %DET for basketball players and WBP showed slower increase with time
      than the sedentary able-bodied control group for three different elbow flexor
      muscles, while no difference was observed for the slope of the %DET between
      basketball and WBP. This result indicated that the athletes are less fatigable
      during the task effort than the nonathletes. Normalized MDF slope decay exhibited
      similar results between the groups as %DET, while the slope of the normalized RMS
      failed to show any significant differences among the groups (p > 0.05). MDF and
      %DET could be useful for the evaluation of muscle fatigue in wheelchair
      basketball training. No conclusions about special training for WBP could be
      determined.

PMID- 22395287
TI  - Optimizing safety and appropriateness of graft use in pelvic reconstructive
      surgery: introduction to the 2nd IUGA Grafts Roundtable.

PMID- 22395288
TI  - Selection of patients in whom vaginal graft use may be appropriate. Consensus of
      the 2nd IUGA Grafts Roundtable: optimizing safety and appropriateness of graft
      use in transvaginal pelvic reconstructive surgery.
AB  - INTRODUCTION AND HYPOTHESIS: The recent rapid and widespread adoption of the use
      of mesh, and mesh-based surgical kits for pelvic organ prolapse (POP) repair
      surgery has occurred largely unchecked, and is now being subjected to critical
      analysis and re-evaluation. METHODS: There have been multiple driving forces for
      this phenomenon, including aggressive marketing by surgical device manufacturing
      companies, contagious hype among pelvic surgeons and regulatory processes which
      facilitated relatively rapid marketing of new devices. RESULTS: Patient-related
      factors such as indications for mesh use, expected risks and benefits relative to
      mesh implantation, and appropriately selected outcome measures have been slow to
      be defined. CONCLUSIONS: This manuscript reviews the currently available
      literature in the use of grafts and mesh in POP surgery with a focus on
      identifying situations where graft use may be appropriate for an individual
      patient. It also identifies specific clinical situations where mesh use may not
      be recommended.

PMID- 22395289
TI  - A standardized description of graft-containing meshes and recommended steps
      before the introduction of medical devices for prolapse surgery. Consensus of the
      2nd IUGA Grafts Roundtable: optimizing safety and appropriateness of graft use in
      transvaginal pelvic reconstructive surgery.
AB  - Over the past decade, a huge number of new implants and ancillary devices have
      been introduced to the market. Most of these have become clinically available
      with little or no clinical data or research. This is a less-than-ideal situation,
      and this subgroup of the ad hoc IUGA roundtable conference wants to open the
      discussion to change this, by proposing a pragmatic minimum clearance track for
      new products being introduced to the market. It consists of an accurate and more
      standardized product description, data on the biological properties gathered in
      animal experiments, anatomical cadaveric studies, and upfront clinical studies
      followed by a compulsory registry on the first 1,000 patients implanted. Ideally,
      manufacturers should support well-designed prospective (randomized) clinical
      trials that can support the claimed benefits of the new product.

PMID- 22395290
TI  - Credentialing for transvaginal mesh placement--a case for "added qualification"
      in competency. Consensus of the 2nd IUGA Grafts Roundtable: optimizing safety and
      appropriateness of graft use in transvaginal pelvic reconstructive surgery.
AB  - INTRODUCTION AND HYPOTHESIS: A process of added qualification of transvaginal
      mesh (TVM) placement is desirable. METHODS: Through a physician-led partnership
      of specialty societies, centers of excellence, and industry, a core curriculum
      encompassing mesh/graft biology, technical skills, and safety can be coupled with
      current educational endeavors instructing surgeons in the use of TVM. A posttest
      process can verify a knowledge-based competency in mesh/graft safety. An auditing
      process after implementation would be optimal. RESULTS: We recommend
      implementation of a five-step process in order to accomplish these goals.
      CONCLUSIONS: It is hoped through these efforts, the ultimate goal of patient
      safety may be reached.

PMID- 22395291
TI  - Informed surgical consent for a mesh/graft-augmented vaginal repair of pelvic
      organ prolapse. Consensus of the 2nd IUGA Grafts Roundtable: optimizing safety
      and appropriateness of graft use in transvaginal pelvic reconstructive surgery.
AB  - INTRODUCTION AND HYPOTHESIS: Complex issues surround informed surgical consent
      for pelvic reconstructive surgery. METHODS: Vaginally placed mesh/grafts are used
      with the intent to increase durability of the repair but potentially introduce
      unique complications, offering new challenges in informed surgical consent
      counseling. RESULTS: Informed consent is a process that takes place throughout
      the entire consultation with the patient. A written document often accompanies
      that process. This paper outlines necessary components of informed surgical
      consent and the theory behind each component. CONCLUSIONS: We explore elements
      that should be included in the consent process with regard to expected benefits,
      alternatives, and material risks that are specific to the use of a mesh/graft
      augmented vaginal repair of prolapse. Included is an appendix that may serve as a
      template for the creation of a surgeon's own written informed consent document.

PMID- 22395293
TI  - Antifungal properties of Japanese cedar essential oil from waste wood chips made
      from used sake barrels.
AB  - In this study, we prepared essential oil (EO) from waste wood chips made from
      used sake barrels (USBs) of Japanese cedar (i.e., EO-USB) by steam distillation.
      We found that EO-USB and three commercially purchased EOs derived from xylem
      tissue of Japanese woods, such as Japanese cedar (Cryptomeria japonica), Japanese
      cypress (Chamaecyparis obtusa) and false arborvitae (Thujopsis dolabrata),
      suppressed fungal growth activity against Trichophyton rubrum, which is the cause
      of tinea disease. The magnitude of the suppressive effects of the EOs ranked as
      follows: T. dolabrata > USB = C. japonica > C. obtusa. These EOs also inhibited
      the activity of DNA polymerase in an extract from T. rubrum mycelia with the
      following ranking: T. dolabrata > USB = C. japonica > C. obtusa. In addition, 50
      ug/ml of EO-USB showed antifungal properties, killing T. rubrum mycelia at 27-42C
      in 20 min. By gas chromatography/mass spectrometry analysis, the main
      sesquiterpenes in EO-USB were delta-cadinene (25.94%) and epi-cubenol (11.55%),
      and the composition of EO-USB was approximately the same as that of EO-C.
      japonica. Three prepared sesquiterpenes, delta-cadinene, epi-cubenol and beta
      eudesmol, inhibited the fungal growth and DNA polymerase activities of T. rubrum,
      and epi-cubenol showed the strongest inhibition among the compounds tested. These
      sesquiterpenes had no inhibitory effects on the activities of other DNA metabolic
      enzymes, such as DNA topoisomerase II, IMP dehydrogenase, polynucleotide kinase
      and deoxyribonuclease from T. rubrum. Taken together, these results suggest that
      EO-USB containing epi-cubenol may be useful for its anti-tinea disease
      properties, which are based on DNA polymerase inhibition.

PMID- 22395294
TI  - Quality outcomes among efficient and inefficient nursing homes: a national study.
AB  - BACKGROUND: With an anticipated increased use of nursing homes to serve an aging
      population in the United States, questions regarding the quality and cost of
      nursing home services come to the fore. Such questions are the concern of nursing
      home residents, their families, private and public payers, policy makers,
      regulators, and nursing home operators. PURPOSES: The purpose of this study was
      to examine the relationship between quality of care and efficiency of nursing
      homes to determine the characteristics of facilities that achieve high quality
      and high efficiency. The study sought also to determine the extent to which
      nursing homes can provide high-quality services and do so with a high level of
      efficiency. METHODOLOGY/APPROACH: This was a cross-sectional study of a 10%
      random sample of U.S. nursing homes, excluding those in hospitals and also those
      with fewer than 20 beds or more than 360 beds. Data sources were the Online
      Survey Certification and Reporting, the Area Resource File database, the U.S.
      Bureau of Labor Statistics, and the U.S. Bureau of Economic Analysis. Data
      envelopment analysis was employed in the analysis of data. FINDINGS: The average
      efficiency of nursing homes was 0.869 (SD = 0.1362), with a statistically
      significant higher average efficiency for nursing homes in urban areas; in
      counties with a higher level of competition, higher average income, or higher
      number of home health agencies; and in not-for-profit and governmental
      facilities. Quality measures were compared between efficient and inefficient
      nursing homes, showing mostly favorable quality outcomes for efficient nursing
      homes. PRACTICE IMPLICATIONS: Families and residents evaluating or in search of
      nursing homes can be confident that high-quality, efficient nursing homes exist.
      Legislators, policy makers, regulators, payers, and administrators can be
      confident that the setting of standards that encourage striving for both quality
      and efficiency simultaneously is indeed realistic.

PMID- 22395295
TI  - Lanthanide-tungstobismuthate clusters based on [BiW9O33]9- building units:
      synthesis, crystal structures, luminescent and magnetic properties.
AB  - The reaction of Na(12)[Bi(2)W(22)O(74)(OH)(2)].44H(2)O,
      Na(9)[BiW(9)O(33)].16H(2)O, lanthanide chloride and Na(2)CO(3) in aqueous
      solution at a pH value of about 7.0 resulted in the three unprecedented giant
      lanthanide-tungstobismuthate clusters Na(x)H(22
      x)[(BiW(9)O(33))(4)(WO(3)){Bi(6)(MU(3)-O)(4)(MU(2)
      OH)(3)}(Ln(3)(H(2)O)(6)CO(3))].nH(2)O {Ln = Pr(3+) (1), Nd(3+) (2), La(3+) (3), x
      = 22 (1), 22 (2), 20 (3), n = 95 (1), 91 (2), 73 (3)}. These three complexes
      represent the first examples of lanthanide ions encapsulated in
      polyoxotungstobismuthates and the largest polytungstobismuthates so far.
      Furthermore, a [{Bi(6)(MU(3)-O)(4)(MU(2)-OH)(3)}](7+) polyoxo cation was
      incorporated into the structure of these compounds. All complexes are
      characterized by single-crystal X-ray diffraction, IR spectra, electronic
      spectroscopy, thermogravimetric and elemental analysis. Magnetic investigation
      revealed that the progressive depopulation of excited Stark sublevels of the
      lanthanide ions at low temperature and the weak antiferromagnetic interaction
      between the neighboring metal centres are responsible for the magnetic properties
      of 1 and 2. The original synthesis strategy in this work may open a gateway to
      assembly of large lanthanide-tungstobismuthates clusters and novel
      multifunctional solid materials in aqueous solution under mild conditions.

PMID- 22395296
TI  - Generation of organotypic raft cultures from primary human keratinocytes.
AB  - The development of organotypic epithelial raft cultures has provided researchers
      with an efficient in vitro system that faithfully recapitulates epithelial
      differentiation. There are many uses for this system. For instance, the ability
      to grow three-dimensional organotypic raft cultures of keratinocytes has been an
      important milestone in the study of human papillomavirus (HPV)(1). The life cycle
      of HPV is tightly linked to the differentiation of squamous epithelium(2).
      Organotypic epithelial raft cultures as demonstrated here reproduce the entire
      papillomavirus life cycle, including virus production(3,4,5). In addition, these
      raft cultures exhibit dysplastic lesions similar to those observed upon in vivo
      infection with HPV. Hence this system can also be used to study epithelial cell
      cancers, as well as the effect of drugs on epithelial cell differentiation in
      general. Originally developed by Asselineau and Prunieras(6) and modified by
      Kopan et al.(7), the organotypic epithelial raft culture system has matured into
      a general, relatively easy culture model, which involves the growth of cells on
      collagen plugs maintained at an air-liquid interface (Figure 1A). Over the course
      of 10-14 days, the cells stratify and differentiate, forming a full thickness
      epithelium that produces differentiation-specific cytokeratins. Harvested rafts
      can be examined histologically, as well as by standard molecular and biochemical
      techniques. In this article, we describe a method for the generation of raft
      cultures from primary human keratinocytes. The same technique can be used with
      established epithelial cell lines, and can easily be adapted for use with
      epithelial tissue from normal or diseased biopsies(8). Many viruses target either
      the cutaneous or mucosal epithelium as part of their replicative life cycle. Over
      the past several years, the feasibility of using organotypic raft cultures as a
      method of studying virus-host cell interactions has been shown for several
      herpesviruses, as well as adenoviruses, parvoviruses, and poxviruses(9).
      Organotypic raft cultures can thus be adapted to examine viral pathogenesis, and
      are the only means to test novel antiviral agents for those viruses that are not
      cultivable in permanent cell lines.

PMID- 22395297
TI  - Perceptions about organ donation among African American, Hispanic, and white high
      school students.
AB  - We applied the Health Belief Model (HBM) to better understand perceptions of
      organ donation among African American, Hispanic, and White high school students.
      We conducted 14 focus groups with 18-year-old students to identify strategies to
      reach this audience when promoting the First-Person Consent Registry (FPCR) for
      organ donation. We found that African American, Hispanic, and White high school
      students are largely unaware of the need for organ donors, and are unfamiliar
      with how to join the FPCR. Participants identified more barriers to joining the
      FPCR than benefits. Two aspects of self-efficacy emerged related to joining the
      FPCR: decisional and task efficacy. Overall, few differences were found with
      respect to organ donation myths across the three ethnic groups. The results are
      discussed, with an emphasis on how the findings compare and contrast with
      previous organ donation research. We focus on message design and dissemination
      strategies for practitioners targeting 18-year-old high school students with
      organ donation promotional materials.

PMID- 22395298
TI  - Amyloid fibril composition as a predictor of development of cardiomyopathy after
      liver transplantation for hereditary transthyretin amyloidosis.
AB  - BACKGROUND: Liver transplantation (LTx) is an accepted treatment for hereditary
      transthyretin (TTR) amyloidosis (ATTR). However, unforeseen heart complications,
      especially a rapid development of cardiomyopathy after LTx has affected mortality
      and morbidity. Recently, a relationship between ATTR-fibril composition and
      cardiomyopathy has been noted. The aim of this study was to investigate whether
      development of cardiomyopathy and heart failure in LTx ATTR amyloid patients is
      related to amyloid fibril composition. METHODS: Twenty-four patients with
      hereditary ATTR amyloidosis who had undergone LTx and have had their amyloid
      fibril type tested were available for the study. They had been examined by
      echocardiography including tissue Doppler and speckle tracking echocardiography
      before and after LTx. Patients were divided into two groups according to fibril
      composition, 10 patients with type A fibrils (a mixture of truncated and full
      length TTR) and 14 patients with type B fibrils (full-length TTR fibrils only).
      There was no difference in time to the follow-up echocardiography between the two
      groups. RESULTS: After LTx, the group consisting of type A patients developed
      symptoms of heart failure and with reduced systolic and diastolic ventricular
      function as shown by echocardiography, whereas no similar deterioration was noted
      for the group of patients with type B fibrils. CONCLUSION: Patients with type A
      fibrils deteriorate an already existing cardiomyopathy and heart failure after
      LTx, in contrast to patients with type B fibrils. These results might have
      significant clinical implications in optimizing best patients selection criteria
      for LTx.

PMID- 22395299
TI  - An informatics agenda for public health: summarized recommendations from the 2011
      AMIA PHI Conference.
AB  - The AMIA Public Health Informatics 2011 Conference brought together members of
      the public health and health informatics communities to revisit the national
      agenda developed at the AMIA Spring Congress in 2001, assess the progress that
      has been made in the past decade, and develop recommendations to further guide
      the field. Participants met in five discussion tracks: technical framework;
      research and evaluation; ethics; education, professional training, and workforce
      development; and sustainability. Participants identified 62 recommendations,
      which clustered into three key themes related to the need to (1) enhance
      communication and information sharing within the public health informatics
      community, (2) improve the consistency of public health informatics through
      common public health terminologies, rigorous evaluation methodologies, and
      competency-based training, and (3) promote effective coordination and leadership
      that will champion and drive the field forward. The agenda and recommendations
      from the meeting will be disseminated and discussed throughout the public health
      and informatics communities. Both communities stand to gain much by working
      together to use these recommendations to further advance the application of
      information technology to improve health.

PMID- 22395300
TI  - Does vitamin B alter the efficacy of botulinum toxin?
AB  - Botulinum toxin prevents acetylcholine release at motor nerve terminals. Group B
      vitamins (B-vit) are essential for proper nerve function. The present study
      addresses the question of whether B-vit accelerate recovery in rat skeletal
      muscle after botulinum toxin A (Btx-A) injection. Forty-four adult male Wistar
      albino rats were used in this experimental study. Rats were divided into three
      groups: group 1 rats were given Btx-A injection only, group 2 rats were given B
      vit supplementation before Btx-A injection, and group 3 rats were given Btx-A and
      B-vit injections together. During the experiment, compound muscle action
      potential (CMAP) of the gastrocnemius muscle was recorded before Btx-A injection
      and sequentially ten times after toxin injection. The statistical significance of
      the CMAP amplitude change among the groups was analyzed. All groups showed
      similar amplitude change between consecutive measurement points. In conclusion,
      combining Btx-A injection with B-vit supplement does not decrease the efficacy of
      the toxin.

PMID- 22395301
TI  - Computer-assisted mandibular reconstruction with vascularized iliac crest bone
      graft.
AB  - BACKGROUND: The intention of mandibular reconstructive surgery is to achieve
      maximum possible functionality, which means the restoration of masticatory
      function and speech with a good esthetic result. METHODS: We compared five
      computer-assisted mandibular reconstructions with 15 conventional mandibular
      reconstructions performed using vascularized iliac crest bone grafts. Based on
      preoperative cone beam computed tomography (CBCT) or CT data imported into the
      specific surgical planning software, a surgical guide was designed by rapid
      prototyping that helped to exactly translate the virtual surgery plan into the
      operation site whereby it fit uniquely to the iliac donor site. The ischemic time
      of the graft was measured intraoperatively and the difference between the amount
      of bone removed and the amount of bone required was determined. In addition, 3
      months after surgery patients had to score the esthetics of their outer
      appearance using a visual analog scale. RESULTS: In all patients the graft fit
      perfectly into the mandibular defect without major adjustments. The time for the
      shaping process of the transplant and the ischemic time were shorter than in the
      conventional grafting procedure. The virtual plan reduced the amount of bone
      removed to the required volume. The patients who underwent computer-assisted
      reconstruction had a higher degree of satisfaction with their outer appearance.
      CONCLUSION: Our clinical experience and the collected data suggest that the
      described method is very promising for optimizing the surgical result of
      mandibular reconstructions using iliac crest bone grafts and achieving an
      excellent esthetic outcome. LEVEL OF EVIDENCE IV: This journal requires that
      authors assign a level of evidence to each article. For a full description of
      these Evidence-Based Medicine ratings, please refer to the Table of Contents or
      the online Instructions to Authors www.springer.com/00266.

PMID- 22395302
TI  - Superselective microcatheter embolization of hemorrhage after buccal lipectomy.
AB  - BACKGROUND: Superselective microcatheter angiography and embolization has been
      shown to be an effective modality for prompt treatment of bleeding from traumatic
      facial injury and refractory epistaxis when local methods fail to achieve
      hemostasis. It obviates the need for further surgical exploration and provides
      precise diagnostic and therapeutic modalities in a minimally invasive manner.
      Despite this successful profile, its use in treatment of hemorrhagic
      complications after facial aesthetic surgery is underreported. This report is a
      unique case of life-threatening hemorrhage after buccal fat pad lipectomy that
      was successfully treated with superselective microcatheter embolization of
      internal maxillary artery branches. METHODS: A 31-year-old male was transferred
      to our emergency room from an outside facility with an active intraoral
      hemorrhage after a buccal lipectomy in which severe bleeding was encountered deep
      within the buccal space that persisted despite further attempts at surgical
      exploration. On arrival to the emergency room, the patient demonstrated signs of
      significant blood loss and had intraoral packing in place tamponading further
      hemorrhage. RESULTS: The patient underwent resuscitation and stabilization with
      endotracheal intubation for airway protection and was sent emergently to the
      angiography suite. Superselective angiography was used to study branches of the
      internal maxillary artery. Superselective embolization using microspheres was
      then performed on target vessels to control the bleeding. The surgical packing
      was then removed with no evidence of active bleeding. The patient was transferred
      to the surgical intensive care unit for further monitoring and was discharged the
      following day in stable condition. CONCLUSION: In the case of refractory surgical
      measures, superselective microcatheter angiography and embolization provides an
      alternative to both precisely localize and control severe small-artery bleeding.
      This may be ideal in cases that otherwise would require extensive dissection and
      in regions of complex anatomy, both of which can compromise aesthetic outcomes.
      We demonstrated the use of this method in a case of refractory bleeding after
      facial lipectomy. The expanding role of superselective angiography and
      specifically designed embolic agents may play an invaluable role in treatment of
      arterial injury after aesthetic surgery when local methods fail. LEVEL OF
      EVIDENCE IV: This journal requires that authors assign a level of evidence to
      each article. For a full description of these Evidence-Based Medicine ratings,
      please refer to the Table of Contents or the online Instructions to Authors at
      www.springer.com/00266.

PMID- 22395303
TI  - Retrospective analysis of treatment of thoracolumbar burst fracture using mono
      segment pedicle instrumentation compared with short-segment pedicle
      instrumentation.
AB  - OBJECTIVE: To investigate the safety and therapeutic effects of mono-segmental
      pedicle instrumentation (MSPI) in treating thoracolumbar burst fracture (AO
      classification: A3.1 and A3.2). METHODS: A retrospective analysis was conducted
      on 60 cases with thoracolumbar burst fracture (AO classification: A3.1 and A3.2)
      between April 2005 and February 2010. Half of the 60 inpatients were treated with
      MSPI, and the other half was treated with short-segment pedicle instrumentation
      (SSPI). The mean operation time, blood loss, visual analog scale (VAS) and
      vertebral kyphotic angle before and after surgery were compared. RESULTS: In the
      MSPI group, the mean operation time was 90 +/- 25 min, and the blood loss at
      operation was 180 +/- 62 ml. The vertebral kyphotic angles were 17.3 degrees  +/-
      9.3 degrees  before surgery, 6.5 degrees  +/- 6.5 degrees  one week after
      surgery, and 9.5 degrees  +/- 6.4 degrees  for the latest follow-up. The VAS
      scores were 7.5 +/- 1.4 before surgery, 2.5 +/- 0.7 one week after surgery, and
      1.4 +/- 0.8 for the latest follow-up. In the SSPI group, the mean operation time
      was 101 +/- 28 min, and the blood loss at operation was 203 +/- 88 ml. The follow
      up duration was 12-64 months. The vertebral kyphotic angles were 16.5 degrees  +/
      9.1 degrees  before surgery, 7.1 degrees  +/- 6.9 degrees  one week after
      surgery, and 7.5 degrees  +/- 5.2 degrees  for the latest follow-up. The VAS
      scores were 6.7 +/- 1.5 before surgery, 3.0 +/- 0.4 one week after surgery, and
      1.1 +/- 0.6 for the latest follow-up. There were no statistically significant
      differences between these two groups in the operation time, blood loss at
      operation, VAS score and vertebral kyphotic angle before and after surgery (p >
      0.05). The post-surgical VAS scores and vertebral kyphotic angles were
      significantly decreased in both groups, compared to before surgery (p < 0.05).
      CONCLUSIONS: It is safe and effective to treat thoracolumbar burst fractures (AO
      3.1 and AO 3.2) with MSPI. The mean operation time, blood loss at operation, post
      surgical VAS and vertebral kyphotic angle of the MSPI group are similar, compared
      to the SSPI group. Further research is needed to find out whether therapeutic
      effects of MSPI are better than those of conservative treatment in these cases.

PMID- 22395304
TI  - Ex vivo observation of human intervertebral disc tissue and cells isolated from
      degenerated intervertebral discs.
AB  - PURPOSE: Disc degeneration, and associated low back pain, are a primary cause of
      disability. Disc degeneration is characterized by dysfunctional cells and loss of
      proteoglycans: since intervertebral tissue has a limited capacity to regenerate,
      this process is at present considered irreversible. Recently, cell therapy has
      been suggested to provide more successful treatment of IVD degeneration. To
      understand the potential of cells to restore IVD structure/function, tissue
      samples from degenerated IVD versus healthy discs have been compared. METHODS:
      Discal tissue from 27 patients (40.17 +/- 11 years) undergoing surgery for
      degenerative disc disease (DDD), DDD + herniation and congenital scoliosis, as
      controls, was investigated. Cells and matrix in the nucleus pulposus (NP) and
      annulus fibrosus (AF) were characterized by histology. AF- and NP-derived cells
      were isolated, expanded and characterized for senescence and gene expression.
      Three-dimensional NP pellets were cultured and stained for glycosaminoglycan
      formation. RESULTS: Phenotypical markers of degeneration, such as cell clusters,
      chondrons, and collagen disorganization were seen in the degenerate samples. In
      severe degeneration, granulation tissue and peripheral vascularization were
      observed. No correlation was found between the Pfirrmann clinical score and the
      extent of degeneration. CONCLUSION: The tissue disorganization in degenerate
      discs and the paucity of cells out of cluster/chondron association, make the IVD
      derived cells an unreliable option for disc regeneration.

PMID- 22395305
TI  - Spine surgery in Italy between neuro and ortho surgeons.

PMID- 22395306
TI  - A new synthetic route for axially chiral secondary amines with binaphthyl
      backbone and their applications in asymmetric Michael reaction of aldehydes to
      nitroalkenes.
AB  - A new synthetic route for binaphthyl-based secondary amines has been developed.
      The key features of this route include the selective direct esterification of the
      binaphthyl structure at the 3- or 3,3'-position and the methylation by a Negishi
      cross-coupling reaction. Based on the new approach, a series of 3-monosubstituted
      and 3,3'-disubstituted chiral secondary amines with a binaphthyl backbone were
      synthesized and screened in the Michael reaction of aldehydes to various
      nitroalkenes. 3-Monosubstituted secondary amine 7c was proved to be the best
      catalyst, affording high yields (up to 95%), good to excellent
      enantioselectivities (up to 99%) and diastereoselectivities (syn/anti up to 99:1)
      under the optimized conditions.

PMID- 22395307
TI  - Students' experiences of learning manual clinical skills through simulation.
AB  - Learning manual skills is a fundamental part of health care education, and motor,
      sensory and cognitive learning processes are essential aspects of professional
      development. Simulator training has been shown to enhance factors that facilitate
      motor and cognitive learning. The present study aimed to investigate the
      students' experiences and thoughts about their learning through simulation skills
      training. The study was designed for an educational setting at a clinical skills
      centre. Ten third-year undergraduate nursing students performed urethral
      catheterisation, using the virtual reality simulator UrecathVisionTM, which has
      haptic properties. The students practised in pairs. Each session was videotaped
      and the video was used to stimulate recall in subsequent interviews. The
      interviews were analysed using qualitative content analysis. The analysis from
      interviews resulted in three themes: what the students learn, how the students
      learn, and the simulator's contribution to the students' learning. Students
      learned manual skills, how to perform the procedure, and professional behaviour.
      They learned by preparing, watching, practising and reflecting. The simulator
      contributed by providing opportunities for students to prepare for the skills
      training, to see anatomical structures, to feel resistance, and to become aware
      of their own performance ability. The findings show that the students related the
      task to previous experiences, used sensory information, tested themselves and
      practised techniques in a hands-on fashion, and reflected in and on action. The
      simulator was seen as a facilitator to learning the manual skills. The study
      design, with students working in pairs combined with video recording, was found
      to enhance opportunities for reflection.

PMID- 22395308
TI  - Music and health. Phenomenological investigation of a medical humanity.
AB  - In response to the tendency for music to be under-represented in the discourse of
      medical humanities, we framed the question 'how can music heal?' We answered it
      by exploring the lived experiences of musicians with lay or professional
      interests in health. Two medical students and a medically qualified
      educationalist, all musicians, conducted a co-operative inquiry with a
      professional musician interested in health. All researchers and six respondents
      kept audio or written diaries. Three respondents were interviewed in depth. A
      medical school head (and experienced musician) critiqued the phenomenological
      analysis of respondents' accounts of music, health, and its relationship with
      undergraduate medical education. Respondents experienced music as promoting
      health, even in seriously diseased people. Music affected people's identity and
      emotions. Through the medium of structure and harmony, it provided a means of
      self-expression that adapted to whatever condition people were in. Music was a
      communication medium, which could make people feel less isolated. Immersion in
      music could change negative states of mind to more positive ones. A transport
      metaphor was commonly used; music 'taking people to better places'. Exercising
      control by becoming physically involved in music enhanced diseased people's self
      esteem. Music was able to bring the spiritual, mental, and physical elements of
      their lives into balance, to the benefit of their wellbeing. Music could help
      medical students appreciate holistically that the state of health of people who
      are either well or diseased can be enhanced by a 'non-technical' intervention.

PMID- 22395311
TI  - A triple helix of double helicates: three hierarchical levels of self-assembly in
      a single structure.
AB  - The bis-bidentate bridging ligand L reacts with Ag(I) ions to form a conventional
      dinuclear [Ag(2)L(2)](2+) double helicate; individual double helicate units
      assemble via Ag...Ag interactions into infinite chains, three of which wrap
      around a central spine of anions to give a triple helical braid, which is
      therefore an infinite triple helix composed of molecular double helicate
      subunits.

PMID- 22395309
TI  - Expressions of putative cancer stem cell markers ABCB1, ABCG2, and CD133 are
      correlated with the degree of differentiation of gastric cancer.
AB  - BACKGROUND: The present study was carried out to determine whether a quantitative
      relationship exists between the expressions of 3 cancer stem cell (CSC) markers
      and the degree of differentiation of gastric cancer. METHODS: The expressions of
      3 putative CSC markers, ABCB1, ABCG2, and CD133, were detected in 90 human
      gastric adenocarcinoma cases by immunofluorescence assay. The differentiation
      statuses of 3 gastric cancer cell lines (the undifferentiated gastric cancer cell
      line HGC-27, the poorly differentiated gastric cancer cell line BGC-823, and the
      moderately-poorly differentiated gastric adenocarcinoma cell line SGC-7901) were
      observed and compared by performing the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl
      tetrazolium bromide (MTT) assay. Gastric xenotransplant cancers in nude mice were
      constructed to compare the malignancy of the 3 variously differentiated gastric
      cancer cell lines. The expressions of the 3 putative CSC markers were also
      detected in the 3 gastric cancer cell lines in vitro by flow cytometric analysis
      and in the 3 gastric xenotransplant cancers in vivo by immunofluorescence
      staining. RESULTS: The expressions of ABCB1, ABCG2, and CD133 were generally
      correlated with the degree of differentiation of the gastric cancers. In the
      human gastric adenocarcinomas and in the cancer cell lines, the expressions of
      ABCB1, ABCG2, and CD133 increased with the increases in the malignancy grades of
      the gastric cancers. In the human gastric adenocarcinomas, poorly differentiated
      adenocarcinoma expressed more ABCB1, ABCG2, and CD133 than well-differentiated
      adenocarcinoma. In addition, the expressions of ABCB1 and CD133 were higher in
      the diffuse type than in the intestinal type of human gastric cancers. The
      undifferentiated cell line HGC-27 expressed more putative CSC markers than the
      moderately-poorly differentiated cell line SGC-7901. Similar results were
      observed in the xenotransplant tumors that arose from the 3 gastric cancer cell
      lines. CONCLUSIONS: The expressions of the CSC markers ABCB1, ABCG2, and CD133
      differed in the gastric cancers with various degrees of differentiation, with
      poorly differentiated gastric cancer expressing relatively more CSC markers.

PMID- 22395312
TI  - Secular changes in Paget's disease: contrasting changes in the number of new
      referrals and in disease severity in two neighboring regions of Spain.
AB  - SUMMARY: We studied the changes in the number of new referrals with Paget's
      disease of bone (PDB) and severity of PDB in a high prevalence focus and its
      neighboring region. Referral of patients changed only in the high prevalence
      focus. The severity of PDB decreased in both regions. These results could suggest
      the effects of an environmental influence on disease activity. INTRODUCTION: The
      prevalence and severity of PDB have decreased in several countries over recent
      years. We previously reported a high radiological prevalence of PDB in
      Vitigudino. Here we sought to determine if secular changes in the number of new
      referrals and severity of PDB had occurred over recent years. METHODS: We studied
      280 patients with clinically diagnosed PDB who were evaluated at a regional
      referral center for metabolic bone disease between 1986 and 2009. Changes in the
      number of new referrals were calculated by relating these data to the number of
      subjects at risk as determined by population registers. Trends in disease
      severity were analyzed with alkaline phosphatase (ALP) activity and disease
      extent on scan. RESULTS: Referrals from the Vitigudino region increased
      substantially between 1986 and 2003 but fell markedly between 2004 and 2009,
      although by this time there had been depopulation of the region due to
      emigration. No significant changes in the rates of referral occurred in the
      remainder of Salamanca. ALP activity and disease extent decreased in Salamanca,
      but only ALP activity decreased in Vitigudino. Referrals rate and severity of PDB
      in Vitigudino were greater than in the remainder of Salamanca. CONCLUSIONS:
      Referral of patients with clinically diagnosed PDB has remained stable for most
      of Salamanca during the past 24 years, but substantial changes have been observed
      in Vitigudino. In agreement with other reports, the severity of PDB has decreased
      in both regions consistent with the effects of an environmental influence on
      disease activity.

PMID- 22395313
TI  - Infection control in home healthcare: an exploratory study of issues for patients
      and providers.
AB  - The number of home healthcare clinicians who have acquired an infection as the
      direct result of patient care is not known. How clinicians practice infection
      prevention and control in home healthcare is also unknown. To describe infection
      prevention and control policies and practices in the home healthcare setting, an
      exploratory study in the form of a 22-question survey was conducted. Findings
      confirm the presence of occupationally acquired infections among home healthcare
      clinicians and that infection prevention and control practices vary widely across
      agencies.

PMID- 22395314
TI  - Molecular oxygen sensing: implications for visceral surgery.
AB  - BACKGROUND: Since mammalian cells rely on the availability of oxygen, they have
      devised mechanisms to sense environmental oxygen tension, and to efficiently
      counteract oxygen deprivation (hypoxia). These adaptive responses to hypoxia are
      essentially mediated by hypoxia inducible transcription factors (HIFs). Three HIF
      prolyl hydroxylase enzymes (PHD1, PHD2 and PHD3) function as oxygen sensing
      enzymes, which regulate the activity of HIFs in normoxic and hypoxic conditions.
      Many of the compensatory functions exerted by the PHD-HIF system are of immediate
      surgical relevance since they regulate the biological response of ischemic
      tissues following ligation of blood vessels, of oxygen-deprived inflamed tissues,
      and of tumors outgrowing their vascular supply. PURPOSE: Here, we outline
      specific functions of PHD enzymes in surgically relevant pathological conditions,
      and discuss how these functions might be exploited in order to support the
      treatment of surgically relevant diseases.

PMID- 22395315
TI  - EGFR regulation of epidermal barrier function.
AB  - Keratinocyte terminal differentiation is the process that ultimately forms the
      epidermal barrier that is essential for mammalian survival. This process is
      controlled, in part, by signal transduction and gene expression mechanisms, and
      the epidermal growth factor receptor (EGFR) is known to be an important regulator
      of multiple epidermal functions. Using microarray analysis of a confluent cell
      density-induced model of keratinocyte differentiation, we identified 2,676 genes
      that are regulated by epidermal growth factor (EGF), a ligand of the EGFR. We
      further discovered, and separately confirmed by functional assays, that EGFR
      activation abrogates all of the known essential processes of keratinocyte
      differentiation by 1) decreasing the expression of lipid matrix biosynthetic
      enzymes, 2) regulating numerous genes forming the cornified envelope, and 3)
      suppressing the expression of tight junction proteins. In organotypic cultures of
      skin, EGF acted to impair epidermal barrier integrity, as shown by increased
      transepidermal water loss. As defective epidermal differentiation and disruption
      of barrier function are primary features of many human skin diseases, we used
      bioinformatic analyses to identify genes that are known to be associated with
      skin diseases. Compared with non-EGF-regulated genes, EGF-regulated genes were
      significantly enriched for skin disease genes. These results provide a systems
      level understanding of the actions of EGFR signaling to inhibit keratinocyte
      differentiation, providing new insight into the role of EGFR imbalance in skin
      pathogenesis.

PMID- 22395317
TI  - Costal cartilage or conchal cartilage for aesthetic and structural reconstruction
      of lower pole ear defects.
AB  - BACKGROUND: Lower pole defects of the ear involve loss of the ear lobule with a
      variable degree of cartilaginous helical rim and antihelix. OBJECTIVES: The
      authors describe a method of reconstructing lower pole ear defects with local
      skin flaps by incorporating conchal or costal cartilage grafts. METHODS: The
      authors retrospectively evaluated the charts of 13 patients who presented between
      1998 and 2007 with lower pole auricular defects. For defects primarily involving
      the earlobe (seven cases), conchal cartilage was sandwiched between an anterior
      transposition flap and a posterior V-Y advancement flap. For defects extending
      into the inferior portions of the helical rim and antihelix (six cases), a costal
      cartilage framework was inserted into a skin pocket and released after six
      months. RESULTS: The mean follow-up for the 13 patients in this series was three
      years. Both techniques resulted in satisfactory long-term outcomes with excellent
      contour of the ear. All patients were satisfied with their reconstruction. Data
      showed that costal cartilage reconstructions required a minimum of two stages and
      that construction with conchal cartilage resulted in a softer lobule but was more
      likely to require minor aesthetic revision. CONCLUSIONS: With appropriate
      preoperative planning, these cartilage graft techniques produce excellent
      aesthetic outcomes in reconstructing complicated defects of the lower pole of the
      ear.

PMID- 22395316
TI  - Genetically determined heterogeneity of lung disease in a mouse model of airway
      mucus obstruction.
AB  - Mucus clearance is an important airway innate defense mechanism. Airway-targeted
      overexpression of the epithelial Na(+) channel beta-subunit [encoded by sodium
      channel nonvoltage gated 1, beta subunit (Scnn1b)] in mice [Scnn1b-transgenic
      (Tg) mice] increases transepithelial Na(+) absorption and dehydrates the airway
      surface, which produces key features of human obstructive lung diseases,
      including mucus obstruction, inflammation, and air-space enlargement. Because the
      first Scnn1b-Tg mice were generated on a mixed background, the impact of genetic
      background on disease phenotype in Scnn1b-Tg mice is unknown. To explore this
      issue, congenic Scnn1b-Tg mice strains were generated on C57BL/6N, C3H/HeN,
      BALB/cJ, and FVB/NJ backgrounds. All strains exhibited a two- to threefold
      increase in tracheal epithelial Na(+) absorption, and all developed airway mucus
      obstruction, inflammation, and air-space enlargement. However, there were
      striking differences in neonatal survival, ranging from 5 to 80%
      (FVB/NJ<BALB/cJ<C3H/HeN<C57BL/6N), which correlated with the incidence of upper
      airway mucus plugging and the levels of Muc5b in bronchoalveolar lavage. The
      strains also exhibited variable Clara cell necrotic degeneration in neonatal
      intrapulmonary airways and a variable incidence of pulmonary hemorrhage and lung
      atelectasis. The spontaneous occurrence of a high surviving BALB/cJ line, which
      exhibited delayed onset of Na(+) hyperabsorption, provided evidence that: 1) air
      space enlargement and postnatal death were only present when Na(+)
      hyperabsorption occurred early, and 2) inflammation and mucus obstruction
      developed whenever Na(+) hyperabsorption was expressed. In summary, the genetic
      context and timing of airway innate immune dysfunction critically determines lung
      disease phenotype. These mouse strains may be useful to identify key modifier
      genes and pathways.

PMID- 22395318
TI  - Development and validation of a new clinically-meaningful rating scale for
      measuring lateral canthal line severity.
AB  - BACKGROUND: Several scales have been employed for evaluating the effects of
      cosmetic treatments in the periorbital area. The Food and Drug Administration
      (FDA) has recently issued new recommendations specifying a rigorous process to
      validate new aesthetic scales. OBJECTIVES: The authors describe and validate a
      new clinical rating scale: the Investigator's Global Assessment of Lateral
      Canthal Line (IGA-LCL) severity scale. METHODS: The new FDA recommendations were
      utilized to validate the new scale. The first step was concept elicitation (based
      on direct input from clinicians, patients, and literature) and evaluation of
      content validity (appropriateness of concepts). The resulting five-point scale
      provided detailed descriptions of the lateral canthal lines (LCL), including
      quantitative assessment of LCL length and depth. Performance parameters,
      including intra- and interrater reproducibility and construct validity, were then
      evaluated in clinical studies. Finally, the scale's threshold for clinically
      meaningful benefit and the ability of the scale to detect change were confirmed
      in two Phase 2b clinical studies involving a total of 270 subjects. RESULTS:
      Content validity was established and the IGA-LCL scale showed excellent
      interrater reliability (weighted Kappa = 0.89) and interrater reliability
      (weighted Kappa = 0.77; Kendall's coefficient of concordance = 0.89). In clinical
      trials, the scale was sensitive enough to detect clinically-meaningful one- and
      two-point changes in LCL severity following treatment with topical botulinum
      toxin type A (BoNT-A). The authors observed statistically-significant
      correlations between the physician-rated IGA-LCL results and patient-reported
      outcomes. CONCLUSIONS: The IGA-LCL scale was shown to be reliable, appropriate,
      and clinically meaningful for measuring LCL severity.

PMID- 22395319
TI  - A new instrument for rhinoplasty: the osteotome with protector and internal
      guide.
AB  - Rhinoplasty is a surgical procedure that demands a high level of intraoperative
      precision as well as maximum vigilance and control. Hump reduction is the most
      common maneuver in aesthetic rhinoplasty, but it is also the most sophisticated,
      dangerous, and difficult to learn. In this article, the authors describe the
      application of an osteotome with a protector and internal guide, which aids in
      achieving the necessary accuracy for hump reduction in safe, easy, and gentle
      manner.

PMID- 22395320
TI  - Current indications for and comparative analysis of three different types of
      latissimus dorsi flaps.
AB  - BACKGROUND: Free tissue transfer with lower abdominal flaps for autologous breast
      reconstruction is not suitable for all patients. The latissimus dorsi (LD)
      musculocutaneous flap is an alternative, effective method for both immediate and
      delayed breast reconstruction. OBJECTIVES: The authors assess their experience
      with LD flaps for breast reconstruction, including indications for patient
      selection, donor site choice, aesthetic outcomes, complications, and patient
      satisfaction. METHODS: Charts for all patients who underwent breast
      reconstruction with one of three types of LD myocutaneous flaps during a three
      year period at a single institution were retrospectively reviewed. Patients (n =
      82) were divided into three groups: (1) 35 patients received a standard LD
      myocutaneous flap with implant, (2) 18 patients underwent a muscle sparing LD
      flap procedure with implant, and (3) 29 patients had an autologous LD flap. A
      questionnaire was administered to assess flap and donor site complications,
      aesthetic outcomes, patient satisfaction, and shoulder function. RESULTS: Flap
      complications occurred in 13 patients (15%). Donor site complications occurred in
      24 patients (28%), mostly consisting of back seroma with the autologous LD flap.
      There was no significant difference in shoulder range of motion or muscle
      strength between the operated and unoperated sides. Patient satisfaction was high
      in all three study groups. CONCLUSIONS: The LD is a safe, versatile, and
      reproducible technique for breast reconstruction. The procedure benefits from
      ease of flap harvesting and setting and may provide satisfactory results in
      diverse patients, including those for whom an abdominal flap is neither indicated
      nor feasible. .

PMID- 22395321
TI  - Commentary on: Breast augmentation and augmentation-mastopexy with local
      anesthesia and intravenous sedation.

PMID- 22395322
TI  - Commentary on: PERTHESE implant-identical cohesive-gel sizers in breast
      augmentation: a prospective study of 200 consecutive cases and implications for
      treatment of breast asymmetry.

PMID- 22395323
TI  - Venous thromboembolism in abdominoplasty: a comprehensive approach to lower
      procedural risk.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a serious and potentially life
      threatening surgical complication. However, there is little consensus regarding
      appropriate VTE prophylaxis for plastic surgery patients. Risk factors as they
      apply to plastic surgery patients are unclear, and recent recommendations for
      chemoprophylaxis in these patients may expose them to other additional risks.
      OBJECTIVES: The authors examine perioperative and intraoperative measures,
      specifically those that have enabled a large number of patients to undergo
      outpatient abdominoplasty safely, with a reduced risk of VTE. METHODS: A
      retrospective review was performed of 404 consecutive abdominoplasty patients who
      were treated at a single outpatient surgery center between 2000 and 2010. Graded
      compression stockings and intermittent pneumatic compression devices were placed
      on all patients, and perioperative and intraoperative warming was strictly
      applied. Progressive tension suturing technique was performed in all cases and
      drains were eliminated. All patients received pain pumps, ambulated within one
      hour of surgery, and were discharged home the same day. Patient VTE risk factors
      were scored with the Caprini/Davison risk assessment model (RAM). Perioperative
      and intraoperative measures were taken to reduce factors that may increase VTE
      risk in abdominoplasty. Complications were recorded, including VTE events,
      seromas, hematomas, and infections. RESULTS: In this series, 247 abdominoplasty
      procedures were performed alone and 157 were combined with additional procedures.
      Under the RAM, 297 patients were considered "high risk" and 17 "highest risk."
      Abdominoplasty operative time was 100 +/- 29 minutes. Only one case of deep vein
      thrombosis (DVT) occurred, in the calf. CONCLUSIONS: A comprehensive approach to
      perioperative and intraoperative patient care has allowed outpatient
      abdominoplasty to be safely performed without VTE chemoprophylaxis in patients
      with fewer than six risk factors.

PMID- 22395324
TI  - Commentary on: Venous thromboembolism in abdominoplasty: a comprehensive approach
      to lower procedural risk.

PMID- 22395325
TI  - Bleeding risks of herbal, homeopathic, and dietary supplements: a hidden
      nightmare for plastic surgeons?
AB  - The utilization of complementary and alternative medicine has increased
      tremendously in the last two decades. Herbal products, homeopathic medicines, and
      dietary supplements are extremely popular and are available without a
      prescription (which likely contributes to their popularity). Despite their
      "natural" characteristics, these remedies have the potential to cause bleeding in
      patients who undergo surgery. The high use of these supplements among cosmetic
      surgery patients, coupled with increasing reports of hematomas associated with
      herbal and homeopathic medicines, prompted the authors to conduct a comprehensive
      review focused on bleeding risks of such products in an effort to raise awareness
      among plastic surgeons. This review focuses on 19 herbs, three herbal formulas,
      two herbal teas, and several other supplements that can cause bleeding
      perioperatively and postoperatively. In addition to being aware of such adverse
      effects, plastic surgeons must adequately screen all patients and educate them on
      the possible dangers associated with these treatments.

PMID- 22395326
TI  - Commentary on: Bleeding risks of herbal, homeopathic, and dietary supplements: a
      hidden nightmare for plastic surgeons?

PMID- 22395327
TI  - The marriage of plastic surgery and social media: a relationship to last a
      lifetime.

PMID- 22395328
TI  - Minimizing capsular contracture in a "clean-contaminated site".

PMID- 22395329
TI  - Histologic proof that acellular dermal matrices (ADM)--Enduragen, DermaMatrix,
      and DuraMatrix--are not repopulated or nonviable and that AlloDerm may be
      repopulated but degraded synchronously.

PMID- 22395330
TI  - Accurately monitoring fluid infiltration during multiple-site or large-volume
      liposuction.

PMID- 22395331
TI  - Technology to the rescue.

PMID- 22395332
TI  - GHGKHKNK octapeptide (P-5m) inhibits metastasis of HCCLM3 cell lines via
      regulation of MMP-2 expression in in vitro and in vivo studies.
AB  - P-5m, an octapeptide derived from domain 5 of HKa, was initially found to inhibit
      the invasion and migration of melanoma cells. The high metastatic potential of
      melanoma cells was prevented by the HGK motif in the P-5m peptide in vitro and in
      an experimental lung metastasis model, suggesting that P-5m may play an important
      role in the regulation of tumor metastasis. The aim of this study was to measure
      the effect of P-5m on tumor metastasis of human hepatocarcinoma cell line
      (HCCLM3) in vitro and in vivo in a nude mouse model of hepatocellular carcinoma
      (HCC), and detect the mechanisms involved in P-5m-induced anti-metastasis. By
      gelatin zymography, matrix metallo-proteinases 2 (MMP-2) activity in HCCLM3 was
      dramatically diminished by P-5m peptide. In addition, the migration and
      metastasis of HCCLM3 cells was also inhibited by the peptide in vitro. In an
      orthotopic model of HCC in nude mice, P-5m treatment effectively reduced the lung
      metastasis as well as the expression of MMP-2 in the tumor tissues. Overall,
      these observations indicate an important role for P-5m peptide in HCC invasion
      and metastasis, at least partially through modulation MMP-2 expression. These
      data suggests that P-5m may have therapeutic potential in metastatic human
      hepatocarcinoma.

PMID- 22395333
TI  - What does/should the minimum clinically important difference measure? A
      reconsideration of its clinical value in evaluating efficacy of lumbar fusion
      surgery.
AB  - OBJECTIVES: The Minimum Clinical Important Difference (MCID) was initially
      intended to provide outcome measures that would be more clinically meaningful
      than measurements based simply on mean improvement in some outcomes. Indeed, a
      basic concept behind the MCID was that statistically significant differences in
      measures did not necessarily reflect clinically meaningful benefits. METHODS:
      This study provides a review of the literature suggesting that the MCID metric is
      not being applied and interpreted in practice in a manner that realizes its
      potential. The MCID has often been used as a means of delineating whether
      patients are "feeling better." This does not, though, necessarily indicate that
      they are "doing better" in terms of physical or socioeconomic functioning.
      RESULTS: The imperfect correlation between "feeling" and "doing" better makes it
      difficult to interpret the clinical implications of articles using MCID measures,
      particularly in the lumbar spine fusion literature. Alternative and more
      scientifically rigorous approaches to the MCID are presented. DISCUSSION: A call
      is made for a more comprehensive approach to synthesize a nearly decade's worth
      of clinical research that has still not yielded consensus concerning the best
      MCID approach to objectively document lumbar spine fusion patients' outcomes.

PMID- 22395334
TI  - Impaired somatosensation in patients with isolated proximal-without-distal
      exercise-related lower-limb ischemia.
AB  - OBJECTIVES: Isolated proximal-without-distal (buttock but not calf) exercise
      related lower-limb ischemia (IPI) might develop in the presence of arterial
      lesions impairing the blood flow supply toward the hypogastric vascular bed. In
      IPI, lower-limb sensory nerve dysfunction might occur from the sacral nerve
      plexus becoming ischemic during exercise. The purpose of this study was to
      compare patients with IPI with healthy controls for the presence of sensory nerve
      dysfunction, as assessed using somatosensory testing (SST). METHODS: Seventeen
      nondiabetic patients with IPI and 17 age-matched and sex-matched healthy controls
      underwent SST of both the upper and lower limbs. RESULTS: The upper-limb SST data
      did not differ between groups (P>0.05). In contrast, lower-limb testing showed
      that patients with IPI had impaired warm (43.4+/-2.7 vs. 40.5+/-4.9 degrees C)
      and vibration (5.0+/-2.3 vs. 6.4+/-1.4 arbitrary units) detection thresholds
      compared with healthy controls (P<=0.05). Furthermore, lower-limb mechanical
      detection threshold and Neuropathy Symptom and Disability Scores tended to be
      higher in the patients (P<=0.10). DISCUSSION: The SST data suggest that patients
      with IPI have abnormal functioning of Abeta-fiber and C-fiber inputs in their
      affected limb(s). These sensory abnormalities might contribute to the exercise
      induced ischemic symptoms experienced by these patients.

PMID- 22395335
TI  - Effects of music engagement on responses to painful stimulation.
AB  - OBJECTIVES: We propose a theoretical framework for the behavioral modulation of
      pain based on constructivism, positing that task engagement, such as listening
      for errors in a musical passage, can establish a construction of reality that
      effectively replaces pain as a competing construction. Graded engagement produces
      graded reductions in pain as indicated by reduced psychophysiological arousal and
      subjective pain report. METHODS: Fifty-three healthy volunteers having normal
      hearing participated in 4 music listening conditions consisting of passive
      listening (no task) or performing an error detection task varying in signal
      complexity and task difficulty. During all conditions, participants received
      normally painful fingertip shocks varying in intensity while stimulus-evoked
      potentials (SEP), pupil dilation responses (PDR), and retrospective pain reports
      were obtained. RESULTS: SEP and PDR increased with increasing stimulus intensity.
      Task performance decreased with increasing task difficulty. Mixed model analyses,
      adjusted for habituation/sensitization and repeated measures within person,
      revealed significant quadratic trends for SEP and pain report (Pchange<0.001)
      with large reductions from no task to easy task and smaller graded reductions
      corresponding to increasing task difficulty/complexity. PDR decreased linearly
      (Pchange<0.001) with graded task condition. We infer that these graded reductions
      in indicators of central and peripheral arousal and in reported pain correspond
      to graded increases in engagement in the music listening task. DISCUSSION:
      Engaging activities may prevent pain by creating competing constructions of
      reality that draw on the same processing resources as pain. Better understanding
      of these processes will advance the development of more effective pain modulation
      through improved manipulation of engagement strategies.

PMID- 22395336
TI  - The WATCHMAN left atrial appendage closure device for atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting an
      estimated 6 million people in the United States (1). Since AF affects primarily
      elderly people, its prevalence increases parallel with age. As such, it is
      expected that 15.9 million Americans will be affected by the year 2050 (2).
      Ischemic stroke occurs in 5% of non-anticoagulated AF patients each year. Current
      treatments for AF include rate control, rhythm control and prevention of stroke
      (3).    The American College of Cardiology, American Heart Association, and
      European Society of Cardiology currently recommended rate control as the first
      course of therapy for AF (3). Rate control is achieved by administration of
      pharmacological agents, such as beta-blockers, that lower the heart rate until it
      reaches a less symptomatic state (3). Rhythm control aims to return the heart to
      its normal sinus rhythm and is typically achieved through administration of
      antiarrhythmic drugs such as amiodarone, electrical cardioversion or ablation
      therapy. Rhythm control methods, however, have not been demonstrated to be
      superior to rate-control methods (4-6). In fact, certain antiarrhythmic drugs
      have been shown to be associated with higher hospitalization rates, serious
      adverse effects (3), or even increases in mortality in patients with structural
      heart defects (7). Thus, treatment with antiarrhythmics is more often used when
      rate-control drugs are ineffective or contraindicated. Rate-control and
      antiarrhythmic agents relieve the symptoms of AF, including palpitations,
      shortness of breath, and fatigue (8), but don't reliably prevent thromboembolic
      events (6).    Treatment with the anticoagulant drug warfarin significantly
      reduces the rate of stroke or embolism (9,10). However, because of problems
      associated with its use, fewer than 50% of patients are treated with it. The
      therapeutic dose is affected by drug, dietary, and metabolic interactions, and
      thus requires detailed monitoring. In addition, warfarin has the potential to
      cause severe, sometimes lethal, bleeding (2). As an alternative, aspirin is
      commonly prescribed. While aspirin is typically well tolerated, it is far less
      effective at preventing stroke (10). Other alternatives to warfarin, such as
      dabigatran (11) or rivaroxaban (12) demonstrate non-inferiority to warfarin with
      respect to thromboembolic events (in fact, dabigatran given as a high dose of 150
      mg twice a day has shown superiority). While these drugs have the advantage of
      eliminating dietary concerns and eliminating the need for regular blood
      monitoring, major bleeding and associated complications, while somewhat less so
      than with warfarin, remain an issue (13-15).    Since 90% of AF-associated
      strokes result from emboli that arise from the left atrial appendage (LAA) (2),
      one alternative approach to warfarin therapy has been to exclude the LAA using an
      implanted device to trap blood clots before they exit. Here, we demonstrate a
      procedure for implanting the WATCHMAN Left Atrial Appendage Closure Device. A
      transseptal cannula is inserted through the femoral vein, and under fluoroscopic
      guidance, inter-atrial septum is crossed. Once access to the left atrium has been
      achieved, a guidewire is placed in the upper pulmonary vein and the WATCHMAN
      Access Sheath and dilator are advanced over the wire into the left atrium. The
      guidewire is removed, and the access sheath is carefully advanced into the distal
      portion of the LAA over a pigtail catheter. The WATCHMAN Delivery System is
      prepped, inserted into the access sheath, and slowly advanced. The WATCHMAN
      device is then deployed into the LAA. The device release criteria are confirmed
      via fluoroscopy and transesophageal echocardiography (TEE) and the device is
      released.

PMID- 22395337
TI  - Molecular dynamics simulations of PfAQP from the malarial parasite Plasmodium
      falciparum.
AB  - Aquaporins (AQPs) are widely distributed in all kingdoms of life and act as
      facilitators in the transport of water and other small solutes through cell
      membranes. Since the plasmodial and human AQPs are different in their primary and
      secondary structure, an intervention targeting plasmodial AQP without affecting
      human AQPs is discussed to identify an attractive novel target against malaria.
      Therefore, it is crucial to understand the action mechanisms of these plasmodial
      AQPs. To explore the progression of the plasmodial real AQPs in vivo at work, a
      molecular dynamic simulation system was successfully developed for a PfAQP
      tetramer in silico. The results showed that the transporting work was not
      synchronous in the four channels at the same time, and that it was different at
      different times in the same channel. The hole sizes varied in different channels
      with time. The structure analysis showed that both hydrophobic and hydrophilic
      residues composed the inner surface of the channels, and the asparagines Asn-193
      and Asn-70 assembled into two motifs of NLA and NPS in the center of the channel
      in place of the signature motifs of NPA in other AQPs. In brief, we successfully
      developed an equilibrated PfAQP-lipid system by molecular dynamics simulations,
      and investigated the structure of the PfAQP channel, which should aid our
      understanding of the AQP structure and its functional implications.

PMID- 22395338
TI  - Surgical outcomes of scoliosis surgery in Marfan syndrome.
AB  - STUDY DESIGN: Retrospective review of a case series. OBJECTIVE: To present the
      radiologic and surgical characteristics of scoliosis treatment in patients with
      Marfan syndrome (MFS). SUMMARY OF BACKGROUND DATA: The treatment of scoliosis in
      MFS has been reported to pose unique challenges. However, the information on
      surgical outcomes is sparse. In clinical practice, surgery for scoliosis in MFS
      is reported to confer higher perioperative risks and instrumentation-related
      complications compared with adolescent idiopathic scoliosis because of atypical
      and rigid curve patterns and the underlying desmogenic disorder. METHODS:
      Database research identified 26 MFS patients treated surgically during 7 years at
      a single spine center. Three patients presented with previous failed surgeries
      and were excluded. The medical records, charts, and radiographs of 23 patients
      were analyzed focusing on curve characteristics, surgical outcomes including
      complications, and curve correction using modern third-generation hybrid or
      pedicle screw systems, and the behavior of junctional segments and compensatory
      curves. RESULTS: The sample included 18 female and 5 male patients with an
      average age of 18.2+/-9.2 years (13-52 y) at index surgery and 21.2+/-9.2 years
      (14-53 y) at follow-up, averaging 35.8+/-23.5 months (6-95 mo). According to the
      Lenke classification, 30% presented as type 1, 9% as type 2, 22% as type 3, 9% as
      type 4, 17% as type 5, and 13% of patients as type 6. Seventy-four percent of
      patients had a type C lumbar modifier. In total, 48% of patients underwent a
      posterior spinal fusion (PSF). Thirty percent had instrumented anterior spinal
      fusion (AISF), whereas 22% had a combined anterior release and staged PSF. Ninety
      one percent of patients achieved solid fusion; there was 1 asymptomatic nonunion
      and 1 recalcitrant nonunion. Add-on phenomena were identified in 13% of patients
      (n=3) treated with AISF, indicating staged PSF once. In total, complications were
      encountered in 30% of patients, indicating redo surgery in 17% of patients. The
      cause for revision included nonunion (2x), liquor leakage (1x), and wound
      infection at the iliac crest (1x). We judged the outcome as excellent/good if the
      patient had no major redo surgery and was very satisfied/satisfied. Overall,
      excellent/good outcome was noted in 78% of the patients. Blood loss averaged 659
      mL in AISF and 1748 mL in PSF. The surgical time was 193 minutes in AISF and 229
      minutes in PSF. Preoperative, postoperative, and follow-up Cobb T4-T12 was 13,
      13, and 16 degrees, respectively; the mean thoracic curves measured 66 (23-106),
      36 (0-58), and 38 degrees (0-58), respectively. Lumbar curves measured 63 (23
      110), 27 (0-80), and 24 degrees (0-68), respectively. Coronal plumb line measured
      2.2, 2.6, and 1.2 cm, respectively, indicating good trunk balance in most
      patients. The flexibility rates of thoracic curves and lumbar curves were 38% and
      47%, respectively. Thoracic curve correction in PSF and combined anterior
      release/PSF was 44%, and in AISF, it reached 57%. CONCLUSIONS: The current study
      highlights the potential pitfalls in scoliosis surgery for patients with MFS.
      Surgery was performed using third-generation pedicle screw-based and hook-based
      systems for PSF and second-generation and third-generation implants for AISF. We
      illustrated that the treatment of scoliosis in MFS, taking into account the
      individual challenges of the underlying desmogenic disorder, can be performed
      with a moderately increased risk for surgical complications compared with
      adolescent idiopathic scoliosis.

PMID- 22395339
TI  - Relaxation of the rigid backbone of an oligoamide-foldamer-based alpha-helix
      mimetic: identification of potent Bcl-xL inhibitors.
AB  - By conducting a structure-activity relationship study of the backbone of a series
      of oligoamide-foldamer-based alpha-helix mimetics of the Bak BH3 helix, we have
      identified especially potent inhibitors of Bcl-x(L). The most potent compound has
      a K(i) value of 94 nM in vitro, and single-digit micromolar IC(50) values against
      the proliferation of several Bcl-x(L)-overexpressing cancer cell lines.

PMID- 22395340
TI  - Diastereoselective synthesis and coordination chemistry of enantiopure keto-bis
      (2-phosphametallocene)s.
AB  - Enantiopure 2-(chlorocarbonyl)phosphametallocenes [MCp*(2-{COCl}-3,4-Me(2)-5-Ph
      PC(4))] (M = Fe, Ru) react with phospholide anions to give 2-phosphametallocene
      2'-acylphospholides K[MCp*(2-CO-2'-{3',4'-Me(2)-5'-PhPC(4)}-3,4-Me(2)-5-Ph
      PC(4))] (M = Fe, Ru) and these have been converted into keto-bis-(2
      phosphametallocene)s through reaction with [FeClCp*(tmeda)]; templation of this
      process with CuBr gives rise to the C(2)- (or pseudo-C(2)- when M = Ru) symmetric
      form of [{MCp*(3,4-Me(2)-5-Ph-PC(4))}(2)-2,2'-(CO)] (M = Fe, Ru; Fe, Fe) with
      high (>95%) diastereoselectivity. X-Ray structures of these ligands coordinated
      to [RuCp*Cl] and [PtCl(2)] centres show that the spatial orientation of the very
      flexible keto-bis-(2-phosphametallocene) structure is highly responsive to the
      coordination sphere of the chelated platinum or ruthenium centre.

PMID- 22395343
TI  - Breast abscess, an early indicator for diabetes mellitus in non-lactating women:
      a retrospective study from rural India.
AB  - INTRODUCTION: Breast abscess is commonly seen in lactating and non-lactating
      women. Diabetes mellitus (DM) frequently predisposes to soft tissue infections
      and has many different presentations. But DM presenting in the form of breast
      abscess is yet to be studied, and we believe our study is the first to explore
      this connection. METHODS: We collected 30 cases of breast abscess in women who
      presented to our hospital from May 2010 to June 2011 retrospectively. They were
      classified into lactating and non-lactating women, and their glycemic status was
      evaluated, together with length of hospital stay, management, recurrence, and
      follow-up status after 6 months. RESULTS: We found that of the 30 patients in our
      study, 20% had high blood sugar levels. And 37.5% of the non-lactating women were
      diagnosed newly with DM. CONCLUSIONS: This study shows that DM can present as
      breast abscess in non-lactating women. Therefore, non-lactating women with a
      breast abscess should be evaluated for DM.

PMID- 22395342
TI  - Update on breast reconstruction techniques and indications.
AB  - Breast reconstruction is considered as part of the breast cancer treatment when a
      mastectomy is required. Implants or expanders are the most frequent techniques
      used for the reconstructions. Expander provides usually a better symmetry. A
      contralateral mastoplasty often is required to improve the symmetry. The nipple
      areola complex, which can be preserved in certain conditions, is usually removed
      and can be reconstructed in a second stage under local anesthesia. In case of
      radical mastectomy and/or radiotherapy, a musculocutaneous flap, such as rectus
      abdominis or latissimus dorsi autologous flaps, is required. When microsurgical
      facilities are available, free or perforator flaps respecting the muscle are
      preferred to decrease the donor site complications. In situ carcinomas or
      prophylactic mastectomy can be reconstructed immediately as well as invasive
      carcinoma according to the recent literature. Locally advanced breast cancer can
      be reconstructed after complete oncologic treatment. Radiotherapy of the thoracic
      wall is proposed in case of lymph node metastases, raising the discussion about
      the technique choice and the timing of the reconstruction. Plastic surgery
      procedures can improve the cosmetic results of the conservative surgery, also
      extending its indications and reducing both mastectomy and reexcision rates.
      Oncoplasty techniques are becoming more and more sophisticated, requiring the
      skill of trained plastic surgeons. Numerous publications confirm the psychosocial
      benefit resulting from the breast reconstruction.

PMID- 22395344
TI  - Laparoscopic-assisted and open high anterior resection within an ERAS protocol.
AB  - BACKGROUND: Due to potentially superior short-term outcomes compared with open
      colorectal surgery, laparoscopic surgery is currently being implemented in
      clinical practice worldwide. In parallel, enhanced recovery after surgery (ERAS)
      programs are shown to improve postoperative recovery in open colorectal surgery.
      This study reports outcomes in laparoscopic versus open surgery in conjunction
      with compliance to the ERAS protocol. METHODS: The association between surgical
      approach (laparoscopic or open surgery), compliance to the ERAS protocol,
      postoperative symptoms, complications, and length of stay after surgery was
      studied. Between January 2007 to December 2010, 114 consecutive patients
      underwent elective high anterior resection with laparoscopic-assisted (n = 55) or
      open resection (n = 59). All clinical data (114 variables) were prospectively
      recorded. RESULTS: The overall preoperative ERAS-protocol compliance was 77% for
      both the laparoscopic and open group. Laparoscopic surgery resulted in shorter
      total length of stay (median 4 vs. 6 days, p = 0.04), earlier pain control
      (median 2 vs. 3 days, p = 0.008), shorter need for intravenous infusions,
      improved mobilization on the first postoperative day (POD1), and lower
      inflammatory response (CRP (POD1) 54 +/- 24 vs. 67 +/- 31 mg/l, p = 0.017)
      compared with open resection. The trends in fewer postoperative complications
      (9.1 vs. 16.9%; odds ratio (OR) 0.55; 95% confidence interval (CI) 0.17-1.81) and
      overall postoperative symptoms delaying recovery (20 vs. 30.5%; OR 0.63; 95% CI
      0.22-1.34) in laparoscopic surgery were not statistically significant.
      CONCLUSIONS: The use of laparoscopy in colorectal surgery within an ERAS protocol
      results in faster recovery compared with open resection.

PMID- 22395345
TI  - Tissue-engineered heart valve: future of cardiac surgery.
AB  - BACKGROUND: Heart valve disease is currently a growing problem, and demand for
      heart valve replacement is predicted to increase significantly in the future.
      Existing "gold standard" mechanical and biological prosthesis offers survival at
      a cost of significantly increased risks of complications. Mechanical valves may
      cause hemorrhage and thromboembolism, whereas biologic valves are prone to
      fibrosis, calcification, degeneration, and immunogenic complications. METHODS: A
      literature search was performed to identify all relevant studies relating to
      tissue-engineered heart valve in life sciences using the PubMed and ISI Web of
      Knowledge databases. DISCUSSION: Tissue engineering is a new, emerging
      alternative, which is reviewed in this paper. To produce a fully functional heart
      valve using tissue engineering, an appropriate scaffold needs to be seeded using
      carefully selected cells and proliferated under conditions that resemble the
      environment of a natural human heart valve. Bioscaffold, synthetic materials, and
      preseeded composites are three common approaches of scaffold formation. All
      available evidence suggests that synthetic scaffolds are the most suitable
      material for valve scaffold formation. Different cell sources of stem cells were
      used with variable results. Mesenchymal stem cells, fibroblasts, myofibroblasts,
      and umbilical blood stem cells are used in vitro tissue engineering of heart
      valve. Alternatively scaffold may be implanted and then autoseeded in vivo by
      circulating endothelial progenitor cells or primitive circulating cells from
      patient's blood. For that purpose, synthetic heart valves were developed.
      CONCLUSIONS: Tissue engineering is currently the only technology in the field
      with the potential for the creation of tissues analogous to a native human heart
      valve, with longer sustainability, and fever side effects. Although there is
      still a long way to go, tissue-engineered heart valves have the capability to
      revolutionize cardiac surgery of the future.

PMID- 22395346
TI  - Toward an improved understanding of isolated upright reflux: positional effects
      on the lower esophageal sphincter in patients with symptoms of gastroesophageal
      reflux.
AB  - BACKGROUND: The purpose of this study was to assess the effect of body position
      on lower esophageal sphincter (LES) structure and function. METHODS: Symptomatic
      patients underwent high-resolution manometry in the supine and upright positions
      followed by pH testing. Regardless of whether there was a positive DeMeester
      score, isolated upright reflux patterns were considered present when the supine
      fraction of time pH <4 = 0%. Predominant-upright and predominant-supine
      bipositional reflux (SBR) patterns were considered present when the supine
      fraction of time was <upright fraction of time pH <4 and the supine fraction was
      >upright fraction of time pH <4, respectively. RESULTS: Of 128 patients, 35
      isolated upright, 55 predominant-upright bipositional, and 27 SBR patients were
      identified. When supine, LES pressure/length was higher in upright compared to
      bipositional reflux patients. When upright, there was no difference in LES
      pressure/length between groups. The LES in isolated upright reflux patients
      became defective when moved from supine to upright position compared to
      bipositional patients, where the LES was defective regardless of position.
      Although the incidence of laryngopharyngeal reflux (LPR) events was comparable
      between groups, isolated upright patients commonly had a normal DeMeester score.
      CONCLUSION: Position impacts LES competency in those with upright reflux and
      would not be detected with supine manometry. Upright reflux can be associated
      with GERD and LPR despite negative pH testing.

PMID- 22395347
TI  - Is there any benefit from expanding the criteria for the resection of
      hepatocellular carcinoma in cirrhotic liver? Experience from a developing
      country.
AB  - BACKGROUND: Patients with large-size (>10 cm) hepatocellular carcinoma (HCC) in
      Child B cirrhosis are usually excluded from curative treatment, i.e., hepatic
      resection, because of marginal liver function and poor outcome. This study was
      designed to evaluate the feasibility of the radiofrequency (RF)-assisted
      sequential "coagulate-cut liver resection technique" in expanding the criteria
      for resection of large HCC in cirrhotic livers with impaired liver function.
      METHODS: Forty patients with Child-Pugh A or B cirrhosis underwent liver
      resection from December 1, 2001 to December 31, 2008. Of these, 20 patients (13
      Child-Pugh A and 7 Child-Pugh B) with advanced stage HCC (stage B and C according
      to Barcelona-Clinic Liver Cancer Group) underwent major liver resection. The two
      groups were comparable in terms of patient age, liver cirrhosis etiology, tumor
      number, and size. RESULTS: All resections were performed without the Pringle
      maneuver. There was no significant difference found between the two groups
      regarding resection time, perioperative transfusion, postoperative complications,
      hospital stay, and day 7 values of hemoglobin and liver enzymes. Likewise, there
      was no significant difference found in the overall survival between Child A and
      Child B patients who underwent major liver resection CONCLUSIONS: RF-assisted
      sequentional "coagulate-cut liver resection technique" may be a viable
      alternative for management of patients with advanced HCC in cirrhotic liver with
      impaired function.

PMID- 22395348
TI  - Indications for surgery and significance of unrecognized cancer in endemic
      multinodular goiter.
AB  - BACKGROUND: The exclusion of cancer in endemic goiter is often difficult mainly
      because of the high number of nodules and the as-yet unclear natural history of
      diagnosed cancer in endemic goiter patients. In a large number of consecutive
      patients who were to undergo total thyroidectomy for endemic multinodular goiter,
      we assessed indications for surgery and thyroid cancer outcome. METHODS: All
      patients who were to undergo total thyroidectomy for diffuse multinodular goiter
      on histological examination between January 1990 and October 2008 were evaluated.
      RESULTS: Of the 1,161 patients included in the study, 252 were cases of thyroid
      cancer (21.7%). Sensitivity of thyroid ultrasound (US) and fine-needle aspiration
      cytology (FNAC) for cancer detection was 30.3 and 64.1%, respectively.
      Differentiated thyroid carcinoma accounted for most of the tumors (96%), with
      54.8% of them being papillary microcarcinomas, while bilateral-multicentric
      cancer occurred in 20.3%. In multivariate analysis, younger age (p = 0.06),
      sonographic findings (p = 0.03), and presence of histological thyroiditis (p =
      0.09) were independently associated with the occurrence of tumors with diameter
      greater than 2 cm. The percentage of transient and permanent postoperative
      complications were approximately 25 and below 2%, respectively. After a median
      follow-up time of 78.5 months, overall recurrence rate was 6.7% and disease
      specific mortality was 1.2%. CONCLUSION: As US and FNAC did not consistently
      detect cancer in patients with diffuse multinodular goiter in our endemic area,
      evidence-based indications for surgery in this group of patients is needed,
      although radical surgery and favorable tumor histology offer favorable outcomes
      in commonly diagnosed thyroid cancer after total thyroidectomy for endemic
      multinodular goiter.

PMID- 22395349
TI  - The age of red blood cells is associated with bacterial infections in critically
      ill trauma patients.
AB  - BACKGROUND: Blood transfusion increases the risk of nosocomial infection in
      trauma patients. Specific patient- and transfusion-related risk factors are
      largely unknown. In this study, risk factors for developing a bacterial infection
      after transfusion of red blood cells (RBC) or platelets were determined in a
      cohort of transfused critically ill trauma patients. MATERIAL AND METHODS: A
      retrospective study was conducted in a mixed medical-surgical Intensive Care Unit
      (ICU) of a level-1 university trauma centre, in trauma patients who received a
      RBC or platelet transfusion. Patients who developed a bacterial infection after
      transfusion were compared to transfused controls who did not develop such an
      infection. Multivariable logistic regression was used to determine risk factors
      for infection. RESULTS: Of the 7,118 patients admitted to the ICU during the
      study period, 196 trauma patients met the inclusion criteria. An infection
      developed in 56 patients (29%). Infection occurred irrespective of the
      administration of antibiotics as part of selective digestive tract
      decontamination, surgery status or Injury Severity Score. Transfusion of RBC
      stored for more than 14 days was associated with infection in trauma patients
      (odds ratio 1.038, [95% CI: 1.01-1.07], p=0.036). Neither the amount of RBC nor
      that of platelets was associated with onset of infection. CONCLUSIONS:
      Transfusion of RBC stored for more then 14 days is a risk factor for onset of
      bacterial infection after trauma, irrespective of the use of prophylactic
      antibiotics. Transfusion of platelets was not a risk factor. These results may
      contribute to designing prospective studies on transfusion of fresh RBC only in
      trauma patients.

PMID- 22395350
TI  - Coagulopathy and transfusion product usage in relation to ruptured abdominal
      aortic aneurysm scoring systems in a tertiary care centre in Japan.

PMID- 22395351
TI  - Prevalence of alloimmunisation in patients with beta thalassaemia major.

PMID- 22395352
TI  - Error management in blood establishments: results of eight years of experience
      (2003-2010) at the Croatian Institute of Transfusion Medicine.
AB  - BACKGROUND: Continuous and efficient error management, including procedures from
      error detection to their resolution and prevention, is an important part of
      quality management in blood establishments. At the Croatian Institute of
      Transfusion Medicine (CITM), error management has been systematically performed
      since 2003. MATERIALS AND METHODS: Data derived from error management at the CITM
      during an 8-year period (2003-2010) formed the basis of this study. Throughout
      the study period, errors were reported to the Department of Quality Assurance. In
      addition to surveys and the necessary corrective activities, errors were analysed
      and classified according to the Medical Event Reporting System for Transfusion
      Medicine (MERS-TM). RESULTS: During the study period, a total of 2,068 errors
      were recorded, including 1,778 (86.0%) in blood bank activities and 290 (14.0%)
      in blood transfusion services. As many as 1,744 (84.3%) errors were detected
      before issue of the product or service. Among the 324 errors identified upon
      release from the CITM, 163 (50.3%) errors were detected by customers and reported
      as complaints. In only five cases was an error detected after blood product
      transfusion however without any harmful consequences for the patients. All errors
      were, therefore, evaluated as "near miss" and "no harm" events. Fifty-two (2.5%)
      errors were evaluated as high-risk events. With regards to blood bank activities,
      the highest proportion of errors occurred in the processes of labelling (27.1%)
      and blood collection (23.7%). With regards to blood transfusion services, errors
      related to blood product issuing prevailed (24.5%). CONCLUSION: This study shows
      that comprehensive management of errors, including near miss errors, can generate
      data on the functioning of transfusion services, which is a precondition for
      implementation of efficient corrective and preventive actions that will ensure
      further improvement of the quality and safety of transfusion treatment.

PMID- 22395353
TI  - Implementation and outcomes of a transfusion-related acute lung injury
      surveillance programme and study of HLA/HNA alloimmunisation in blood donors.
AB  - BACKGROUND: Transfusion-related acute lung injury (TRALI) is the leading cause of
      transfusion-associated mortality. Antibodies against human leucocyte antigens
      (HLA) and human neutrophil antigens (HNA) are often detected in the implicated
      donors. We investigated the incidence and aetiology of TRALI in Lombardy.
      Moreover, we determined the rate of HLA and HNA alloimmunisation and the HNA
      genotype in a cohort of local blood donors. MATERIALS AND METHODS: During a 2
      year observational study in eight blood transfusion services, suspected TRALI
      cases were collected and characterised by means of HLA and HNA antibody screening
      of implicated donors, donor/recipient cross-matching and HLA/HNA molecular
      typing. In addition, 406 Italian donors were evaluated for alloimmunisation and
      in 102 of them HNA gene frequencies were determined. RESULTS: Eleven cases were
      referred to the central laboratory, of whom three were diagnosed as having TRALI,
      seven as having possible TRALI and one as having transfusion-associated
      circulatory overload. Seven TRALI cases were immune-mediated whereas in three we
      did not find either alloantibodies in implicated donors or a positive reaction in
      the cross-match. The most frequently implicated blood component was red blood
      cells (in 5 males and in 1 female), whereas four cases of TRALI were associated
      with transfusion of fresh-frozen plasma (in 3 females and in 1 male). The
      frequency of reported TRALI/possible TRALI cases was 1:82,000 for red blood cells
      and 1:22,500 for fresh-frozen plasma. No cases were observed for platelets.
      Overall, the frequency of HLA or HNA alloimmunisation in blood donors was 29% for
      females and 7% for males. The latter could be related, at least in part, to
      natural antibodies. HNA gene frequencies showed that HNA-1b is more frequent than
      HNA-1a in our sample of donors. DISCUSSION: The recently adopted national policy
      to prevent TRALI, i.e. using only plasma donated by males, would have had a
      positive impact in our setting.

PMID- 22395354
TI  - Allogeneic platelet leucocyte-gel to treat occipital decubitus ulcer in a
      neonate: a case report.

PMID- 22395355
TI  - Use of blood products and risk of stroke after coronary artery bypass surgery.
AB  - BACKGROUND: The impact of blood transfusion on the development of post-operative
      stroke after coronary artery bypass grafting (CABG) is not well established. We,
      therefore, investigated this issue. MATERIALS AND METHODS: Complete data on peri
      operative blood transfusion were available for 2,226 patients who underwent CABG
      in three Finnish hospitals. RESULTS: Stroke occurred post-operatively in 53
      patients (2.4%). Logistic regression showed that pre-operative creatinine (OR
      1.003, 95% CI 1.000-1.006), extracardiac arteriopathy (OR 2.344, 95% CI 1.133
      4.847), pre-operative atrial fibrillation (OR 2.409, 95% CI 1.149-5.052), and the
      number of packed red blood cell units transfused (OR 1.121, 95% CI 1.065-1.180)
      were significantly associated with post-operative stroke. When the various blood
      product transfusions instead of transfused units were included in the
      multivariable analysis, solvent/detergent treated plasma (Octaplas) transfusion
      (OR 2.149, 95% CI 1.141-4.047), but not red blood cell transfusion, was
      significantly associated with postoperative stroke. Use of blood products ranging
      from no transfusion (stroke rate 1.6%) to combined transfusion of red blood
      cells, platelets and Octaplas was associated with a significant increase in post
      operative stroke incidence (6.6%, adjusted analysis: OR 1.727, 95% 1.350-2.209).
      Patients who received >2 units of red blood cells, >4 units of Octaplas units and
      >8 units of platelets had the highest stroke rate of 21%. CART analysis showed
      that increasing amount of transfused Octaplas, platelets and history of
      extracardiac arteriopathy were significantly associated with post-operative
      stroke. CONCLUSIONS: Transfusion of blood products after CABG has a strong, dose
      dependent association with the risk of stroke. The use of Octaplas and platelet
      transfusions seem to have an even larger impact on the development of stroke than
      red blood cell transfusions.

PMID- 22395356
TI  - No evidence of xenotropic murine leukaemia virus-related virus in French blood
      donors.

PMID- 22395358
TI  - Long-term molecular response after discontinuation of interferon-alpha in two
      patients with chronic myeloid leukaemia.

PMID- 22395357
TI  - Single-dose pegylated-filgrastim versus daily filgrastim after high-dose
      chemotherapy and autologous stem cell transplantation for lymphoid malignancies:
      delayed platelets recovery?

PMID- 22395360
TI  - The EuroChimerism concept for a standardized approach to chimerism analysis after
      allogeneic stem cell transplantation.
AB  - Hematopoietic stem cell transplantation is becoming an increasingly important
      approach to treatment of different malignant and non-malignant disorders. There
      is thus growing demand for diagnostic assays permitting the surveillance of
      donor/recipient chimerism posttransplant. Current techniques are heterogeneous,
      rendering uniform evaluation and comparison of diagnostic results between centers
      difficult. Leading laboratories from 10 European countries have therefore
      performed a collaborative study supported by a European grant, the EuroChimerism
      Concerted Action, with the aim to develop a standardized diagnostic methodology
      for the detection and monitoring of chimerism in patients undergoing allogeneic
      stem cell transplantation. Following extensive analysis of a large set of
      microsatellite/short tandem repeat (STR) loci, the EuroChimerism (EUC) panel
      comprising 13 STR markers was established with the aim to optimally meet the
      specific requirements of quantitative chimerism analysis. Based on highly
      stringent selection criteria, the EUC panel provides multiple informative markers
      in any transplant setting. The standardized STR-PCR tests permit detection of
      donor- or recipient-derived cells at a sensitivity ranging between 0.8 and 1.6%.
      Moreover, the EUC assay facilitates accurate and reproducible quantification of
      donor and recipient hematopoietic cells. Wide use of the European-harmonized
      protocol for chimerism analysis presented will provide a basis for optimal
      diagnostic support and timely treatment decisions.

PMID- 22395361
TI  - Targeting microRNA-30a-mediated autophagy enhances imatinib activity against
      human chronic myeloid leukemia cells.
AB  - A major advancement in the treatment of chronic myeloid leukemia (CML) has been
      the development of imatinib and other BCR-ABL tyrosine kinase inhibitors.
      MicroRNAs (miRNAs) are small RNA molecules that influence gene expression by post
      transcriptional regulation of messenger RNA. It is not yet clear how miRNAs are
      able to regulate the effectiveness of imatinib in CML. Here, we show that
      imatinib markedly inhibits expression of miR-30a in human CML cells. miR-30a is a
      potent inhibitor of autophagy by downregulating Beclin 1 and ATG5 expression. miR
      30a mimic or knockdown of autophagy genes (ATGs) such as Beclin 1 and ATG5 by
      short hairpin RNA enhances imatinib-induced cytotoxicity and promotes
      mitochondria-dependent intrinsic apoptosis. In contrast, knockdown of miR-30a by
      antagomir-30a increases the expression of Beclin 1 and ATG5, and inhibits
      imatinib-induced cytotoxicity. These findings indicate that dysregulation of miR
      30a may interfere with the effectiveness of imatinib-mediated apoptosis by an
      autophagy-dependent pathway, thus representing a novel potential therapeutic
      target in CML.

PMID- 22395362
TI  - Metformin and reprogramming into iPSCs.

PMID- 22395363
TI  - A role of miR-33 for cell cycle progression and cell proliferation.

PMID- 22395364
TI  - A national evaluation of community-based youth cessation programs: end of program
      and twelve-month outcomes.
AB  - Most youth cessation treatment research consists of efficacy studies in which
      treatments are evaluated under optimal conditions of delivery. Less is known
      about the effectiveness of youth cessation treatments delivered in real-world,
      community based settings. A national sample of 41 community-based youth cessation
      programs participated in a longitudinal evaluation to identify site, program, and
      participant characteristics associated with successful cessation. Validated quit
      rates were comparable to those in randomized controlled trials; 7-day abstinence
      at the end of program averaged 14% and 30-day abstinence at 12 months averaged
      12%. Multivariate GEE models explored predictors of smoking cessation at the end
      of the programs and at 12 months. Results showed correlates of both short- and
      long-term cessation. Findings point to the importance of both individual and
      community-level variables, including motivation, opportunities for and
      encouragement to engage in activities outside of academics, having youth
      participate in treatment before they become highly dependent smokers, and
      community norms and ordinances that discourage youth purchase, use and possession
      of tobacco. Providing evidence-based treatment to youth in community-based
      settings results in successful cessation.

PMID- 22395365
TI  - Digital animation as a method to disseminate research findings to the community
      using a community-based participatory approach.
AB  - Community-based participatory research (CBPR) has garnered increasing interest
      over the previous two decades as researchers have tackled increasingly complex
      health problems. In academia, professional presentations and articles are major
      ways that research is disseminated. However, dissemination of research findings
      to the people and communities who participated in the research is many times
      forgotten. In addition, little scholarly literature is focused on creative
      dissemination of research findings to the community using CBPR methods. We seek
      to fill this gap in the literature by providing an exemplar of research
      dissemination and partnership strategies that were used to complete this project.
      In this paper, we present a novel approach to the dissemination of research
      findings to our targeted communities through digital animation. We also provide
      the foundational thinking and specific steps that were taken to select this
      specific dissemination product development and distribution strategy.

PMID- 22395367
TI  - [Editorial: management of acute coronary syndromes in patients presenting without
      persistent ST-segment elevation: what has changed in the new European Society of
      Cardiology guideline?].

PMID- 22395366
TI  - Preparing individual Drosophila egg chambers for live imaging.
AB  - Live cell imaging is an important technique applied to a number of Drosophila
      tissues used as models to investigate topics such as axis specification, cell
      differentiation and organogenesis (1). Correct preparation of the experimental
      samples is a crucial, often neglected, step. The goal of preparation is to ensure
      physiological relevance and to establish optimal imaging conditions. To maintain
      tissue viability, it is critical to avoid dehydration, hypoxia, overheating or
      medium deterioration (2). The Drosophila egg chamber is a well established system
      for examining questions relating, but not limited, to body patterning, mRNA
      localization and cytoskeletal organization (3,4). For early- and mid-stage egg
      chambers, mounting in halocarbon oil is good for survival in that it allows free
      diffusion of oxygen, prevents dehydration and hypoxia and has superb optical
      properties for microscopy. Imaging of fluorescent proteins is possible through
      the introduction of transgenes into the egg chamber or physical injection of
      labeled RNA, protein or antibodies (5-7). For example, addition of MS2 constructs
      to the genome of animals enables real time observation of mRNAs in the oocyte
      (8). These constructs allow for in vivo labeling of mRNA through utilization of
      the MS2 bacteriophage RNA stem loop interaction with its coat protein (9). Here,
      we present a protocol for the extraction of ovaries as well as isolating
      individual ovarioles and egg chambers from the female Drosophila. For a detailed
      description of Drosophila oogenesis see Allan C. Spradling (1993, reprinted 2009)
      (10).

PMID- 22395368
TI  - The product of eGFR and hemoglobin may help predict mortality in systolic heart
      failure patients without severe anemia and renal failure.
AB  - OBJECTIVES: Cardiorenal anemia syndrome is defined in patients with heart failure
      (HF). Although individual influences of renal impairment and anemia were shown
      previously, complex interaction between the kidney, bone marrow, and the heart
      renders decision making relatively inefficient in patients with milder forms of
      these diseases. We aimed to investigate whether product of estimated glomerular
      filtration rate (eGFR) and hemoglobin (Hb) predicts outcomes in patients with HF.
      STUDY DESIGN: The study included 148 consecutive patients (89 males, 59 females;
      mean age 68+/-10 years) who were hospitalized with acutely decompensated systolic
      HF and discharged alive. Discharge Hb levels were measured. Renal function was
      estimated via the MDRD (Modification of Diet in Renal Disease) formula. The
      eGFRxHb product was derived, and cut-off was defined using the ROC (receiver
      operating characteristic) analysis. The influence of eGFRxHb product on mortality
      was analyzed after a follow-up period of up to 34 months (mean 8.2+/-5.5 months).
      RESULTS: The mean Hb was 12.7+/-2 g/dl, the mean creatinine was 105+/-46 umol/l,
      and the mean eGFR was 61+/-23 ml/min/1.73 m2. Eighty-two patients (55.4%) had an
      eGFR of <60 ml/kg/m2. During the follow-up, 27 patients died. Optimal cut-off
      level of eGFRxHb product to predict mortality was found to be <=788 with a
      sensitivity of 82.6% and specificity of 51.3%. In multivariate Cox proportional
      analysis, only eGFRxHb product <=788 (HR 4.488, 95% CI 1.500-13.433, p=0.007) and
      presence of atrial fibrillation (HR 2.644, 95% CI 1.113-6.280, p=0.028) were
      independent predictors of mortality in patients with HF. CONCLUSION: We concluded
      that the product of eGFR and Hb might be useful in prediction of mortality among
      patients with systolic HF.

PMID- 22395369
TI  - Assessment of P-wave dispersion in patients with isolated bicuspid aortic valve
      and its relationship with aortic elasticity.
AB  - OBJECTIVES: We evaluated P-wave duration and P-wave dispersion (PWD) in patients
      with isolated bicuspid aortic valve (BAV) without significant valve dysfunction
      and investigated the relationship between P-wave measurements and aortic
      elasticity. STUDY DESIGN: This prospective study consisted of 39 patients with
      isolated BAV with normal ejection fraction and 29 age- and gender-matched healthy
      subjects. P-wave duration and P-wave dispersion were calculated on 12-lead
      electrocardiograms. Echocardiographic examination was performed and aortic
      elasticity parameters were calculated including aortic strain, aortic stiffness
      index, aortic distensibility, and aortic elastic modulus. RESULTS: Patients with
      BAV had significantly greater Pmax and PWD compared to controls (128+/-11 vs.
      115+/-11 msec, p=0.006; 70+/-10 vs. 66+/-13 msec, p=0.02, respectively), whereas
      Pmin was similar. Aortic strain and distensibility were significantly lower and
      aortic stiffness index and aortic elastic modulus were significantly greater in
      patients with BAV (for all, p=0.0001). In correlation analysis, Pmax was
      significantly correlated with aortic strain (r=-0.30, p=0.01), aortic
      distensibility (r=-0.27, p=0.02), aortic stiffness index (r=0.36, p=0.004), and
      aortic elastic modulus (r=0.38, p=0.003), while PWD was correlated with aortic
      strain (r=-0.23, p=0.05) and aortic elastic modulus (r=0.25, p=0.05). CONCLUSION:
      Our data showed that isolated BAV without valve dysfunction was associated with
      prolonged P-wave duration and increased PWD, both of which were related to aortic
      elasticity parameters.

PMID- 22395370
TI  - [Long term follow-up of 799 children with isolated ventricular septal defects].
AB  - OBJECTIVES: We evaluated long-term follow-up results and prognosis of pediatric
      patients with isolated ventricular septal defects (VSD). STUDY DESIGN: The study
      included 799 patients (368 girls, 431 boys; mean age at diagnosis 24.3+/-37.4
      months; median 6 months) who were monitored by the pediatric cardiology
      department for VSD. The mean follow-up period was 32.8+/-30.3 months (median 20
      months). RESULTS: The VSDs were classified as perimembranous (n=610, 76.4%),
      muscular (n=171, 21.4%), doubly committed subarterial (n=10, 1.3%), and multiple
      (n=8, 1%). Spontaneous closure rates were 42.7%, 13.1%, and 25% in muscular,
      perimembranous, and multiple VSDs, respectively, which corresponded to a mean age
      of 18.6+/-19.9 months (median 12 months) in muscular and 30.2+/-33.7 months
      (median 14.5 months) in perimembranous VSDs. Before 2 years of age, 78.1% of
      muscular and 58.6% of perimembranous VSDs underwent spontaneous closure. Of 256
      defects (32%) that required surgical closure, 91.4% were of perimembranous
      location. The mean age at surgery was 38.8+/-49.1 months (median 11 months) for
      muscular, and 43.7+/-40.9 months (median 24 months) for perimembranous defects.
      During the follow-up period, the following complications were noted: aortic valve
      prolapse (0.7%), aortic regurgitation (0.6%), left ventricle-to-right atrium
      shunt (2.6%), subaortic ridge (3.7%), and infundibular stenosis (1.2%). Aortic
      regurgitation developed in eight patients (3.7%) after surgical closure.
      CONCLUSION: Our data on the natural course and prognosis of VSDs may be of
      relevance with respect to patients' age, defect type, and complications
      encountered in the follow-up period.

PMID- 22395371
TI  - [Changes in etiology, cause of death, survival, and mortality rates in cardiac
      transplant patients from 1998 to 2011].
AB  - OBJECTIVES: We retrospectively analyzed changes in heart failure etiology, causes
      of death, mortality and survival rates in cardiac transplant patients from 1998
      to 2011. STUDY DESIGN: A total of 144 patients (112 men, 32 women; mean age
      40.2+/-14.3 years) underwent cardiac transplantation between February 1998 and
      January 2011. The patients were divided into two groups; hence, 63 patients
      (group 1; mean age 42.5+/-12.6 years) receiving transplantation up to January
      2006, and 81 patients (group 2; mean age 38.4+/-15.3 years) receiving
      transplantation from 2006 to 2011. In the latter period, a ventricular assist
      device was used in 17 patients before transplantation. RESULTS: Dilated
      cardiomyopathy was the main cause of heart transplantation in both groups (71.4%
      vs. 74.1%). Overall mortality, in-hospital mortality (<30 days), and late
      mortality (>=30 days) rates were 39.6% (n=57), 13.9% (n=20), and 25.7% (n=37),
      respectively. Survival rates for 1, 2, 5, and 10 years were 76%, 69%, 59%, and
      46%, respectively. The second group had significantly lower rates of overall
      mortality and late mortality compared to group 1 (29.6% vs. 52.4%, p=0.005; 16.0%
      vs. 38.1%, p=0.002, respectively), whereas early mortality rates were similar.
      Survival rates were also higher in the second group, but these differences did
      not reach significance (1-year, 76.1% vs. 74.6%; 2-year, 73.0% vs. 65.1%; 5-year,
      63.8% vs. 55.6%; log rank 0.33). In both groups, infections (30.3% vs. 33.3%),
      right ventricular failure (12.1% vs. 29.2%), and sudden cardiac death (15.2% vs.
      16.7%) were the leading causes of death. CONCLUSION: Our data show that overall
      and late mortality rates show significant decreases in cardiac transplant
      patients from 1998 to 2011.

PMID- 22395372
TI  - [The frequency of aspirin resistance by a modified thrombelastography method and
      its relationship with clinical and laboratory parameters in patients with stable
      coronary artery disease].
AB  - OBJECTIVES: Aspirin is the cornerstone of antiplatelet therapy in cardiovascular
      medicine. However, aspirin resistance has been demonstrated in 0.4% to 83.3% of
      aspirin-receiving patients. The aim of this study was to investigate the
      frequency of aspirin resistance using a modified thrombelastography (mTEG) method
      and related clinical and biochemical parameters in patients with stable coronary
      artery disease (CAD), who received 100 mg/day aspirin. STUDY DESIGN: The study
      included 168 patients (115 males, 53 females; mean age 60+/-8 years) with stable
      CAD, receiving aspirin at a dose of 100 mg/day. Aspirin responsiveness was
      determined using mTEG, where aspirin resistance was defined as arachidonic acid
      induced whole blood platelet aggregation inhibition (PAI) of less than 50%.
      RESULTS: Aspirin resistance was detected in 27 patients (16.1%). Platelet
      aggregation inhibition showed negative correlations with hyperlipidemia, smoking,
      spironolactone use, systolic blood pressure, pulse pressure, and total
      cholesterol and fibrinogen levels. In multivariate regression analysis, only
      fibrinogen level (OR=1.063, p=0.010) and pulse pressure (OR=1.197, p=0.023) were
      found to be independent indicators of aspirin resistance and PAI. In ROC
      analysis, cut-off values of 50 mmHg for pulse pressure and 400 mg/dl for
      fibrinogen level predicted aspirin resistance with 88.9% and 74% sensitivity and
      64.4% and 68% specificity, respectively. CONCLUSION: Our findings suggest that
      measurements of fibrinogen level and pulse pressure may be used as easy and
      reliable methods in predicting aspirin resistance.

PMID- 22395373
TI  - [Top 50 articles from Turkey contributing to cardiovascular medicine].
AB  - OBJECTIVES: To determine and disclose publications from Turkey that have most
      contributed "genuinely" to cardiovascular medicine in the past 40 years. STUDY
      DESIGN: Based on data of Web of Science, 50 publications were identified,
      originating from Turkey's institutions and having received the greatest number of
      citations as of July 2011. Papers having more than a minor share by international
      authors were not considered. RESULTS: Thirty-eight primary authors generated 50
      medical papers, each receiving >=37 citations (95% CI 37; 124). The herein cited
      articles corresponded in quality to the top one-fifth of global papers. Half of
      the articles were published in 1997-2003. Currently, the estimated number of such
      papers produced annually in Turkey is only 4-5, which represents only a global
      share of 1.0 per mille. The best period registered were the years 1995 to 2005,
      after which a rise is not anticipated to persist. Cardiology generated 29,
      cardiovascular surgery 19, and pediatric cardiology two articles. These
      publications originated from only 10 medical faculties, Gulhane Military Academy,
      three state and two private hospitals. CONCLUSION: Given its potential, the
      performance of Turkey's contribution to cardiovascular medicine has been
      unsatisfactory. A much larger concerted effort is required to form a milieu that
      will focus to enhance research having a potential to contribute to medicine.

PMID- 22395374
TI  - Two adult cases of anomalous left coronary artery from the pulmonary artery.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      is a rare congenital anomaly that presents as left-sided heart failure and mitral
      valve insufficiency during the first months of life. However, some cases may
      benefit from sufficient collateral blood supply from the right coronary artery,
      resulting in increased survival even to advanced ages. Herein, we report on two
      adult cases of ALCAPA, namely, a 52-year-old male patient that presented with
      angina and a 70-year-old female patient presenting with stroke, dyspnea, and
      pretibial edema. In both cases, ALCAPA was demonstrated by coronary angiography
      and multislice computed tomography angiography. The younger patient refused
      surgery and remained asymptomatic and event-free during a two-year follow-up with
      anti-ischemic medications, while the older with high surgical risk was considered
      for intracardiac defibrillator implantation along with medical therapy.

PMID- 22395375
TI  - Asymptomatic course of a metastatic mass completely filling the right atrium in a
      patient with hepatocellular carcinoma.
AB  - Intracardiac involvement rarely develops in patients with hepatocellular
      carcinoma (HCC) and its prognosis is poor. Patients generally have symptoms of
      sudden dyspnea or massive lower extremity edema and the clinical course may be
      further complicated by many fatal cardiovascular complications. Absence of
      cardiac symptoms or findings, however, is an unusual condition. We present a 61
      year-old man with HCC who was incidentally found to have an intracavitary mass
      completely occupying the right atrium. He had no cardiac complaints, nor any
      signs of cardiac involvement. The mass was first detected by computed tomography
      and then confirmed by transthoracic echocardiography. The patient underwent a
      successful surgical resection and the histopathologic diagnosis was HCC.
      Unfortunately, the postoperative course was complicated by the development of
      acute kidney failure and, despite hemodialysis treatment, the patient died of
      kidney failure eight days after the operation.

PMID- 22395376
TI  - Percutaneous closure of a postoperative residual atrial septal defect with the
      Occlutech Figulla Occluder device.
AB  - A 67-year-old male patient with an eight-month history of operation for mitral
      valve repair and secundum atrial septal defect (ASD) presented with complaints of
      fatigue and shortness of breath. Transthoracic echocardiography showed a residual
      ASD resulting from separation of a pericardial patch. Qp/Qs rate was 3.2. The
      diameter of the residual defect measured by transesophageal echocardiography was
      18 mm. During right heart catheterization, pulmonary artery pressure was
      estimated to be 50 mmHg. Using the percutaneous method accompanied by
      transesophageal echocardiography guidance, the residual defect was successfully
      closed with a 21-mm Occlutech Figulla device. Postprocedural echocardiographic
      control showed no leaks. The patient was discharged with 300 mg/day aspirin
      treatment.

PMID- 22395377
TI  - [Development of heart failure and stroke in the setting of myocardial
      noncompaction].
AB  - We present a 30-year-old male patient who developed new-onset heart failure and
      stroke in the setting of myocardial noncompaction. He presented with shortness of
      breath that progressively worsened in the past 15 days. Chest X-ray showed
      diffuse bilateral infiltration with bilateral hilar fullness. Electrocardiography
      showed sinus rhythm, signs of left ventricular hypertrophy, and diffuse T-wave
      negativity. Transthoracic echocardiography demonstrated moderate systolic
      dysfunction of the left ventricle and trabeculations and intertrabecular recesses
      in the anterolateral and apical regions of the inferior wall. Dense spontaneous
      echo contrast was seen in the left ventricular cavity. He also had a bicuspid
      aortic valve. The patient developed stroke at the eighth hour of hospitalization.
      Heparin infusion and heart failure treatment were started. Transesophageal
      echocardiography showed no thrombus. Clinical and radiological findings improved
      significantly during the follow-up. Oral anticoagulant therapy was initiated and
      the patient was discharged with control recommendations. Myocardial noncompaction
      was also demonstrated by cardiac magnetic resonance imaging.

PMID- 22395378
TI  - [Coronary optical coherence tomography in late stent thrombosis: the first
      application in Turkey].
AB  - Stent thrombosis remains an unresolved problem despite advances in coronary
      revascularization. Incomplete stent apposition (malapposition) and incomplete
      endothelialization of stent struts, which is more commonly seen with drug-eluting
      stents, are the primary causes of late or very late stent thrombosis. Optical
      coherence tomography (OCT) is a novel modality for imaging of these potentially
      fatal conditions. Coronary angiography performed for non-ST elevation myocardial
      infarction in a 60-year-old male patient with a three-year history of sirolimus
      eluting stent implantation to the left anterior descending coronary artery showed
      stent thrombosis. In addition to his regular aspirin and clopidogrel therapy,
      heparin and tirofiban infusions were started. Repeat coronary angiography five
      days later showed nearly complete disappearance of the thrombus. Further
      examination with OCT to evaluate stent malapposition and endothelialization
      revealed separation of stent struts from the vessel wall. Balloon dilatation was
      performed and complete apposition of the stent struts against the vessel wall was
      achieved, which was further confirmed by OCT. This represents the first OCT
      application in our country in a case of very late stent thrombosis.

PMID- 22395379
TI  - [Late diagnosis of corrected transposition of the great arteries in an elderly
      patient with coronary artery disease].
AB  - Congenitally corrected transposition of the great arteries (c-TGA) is a rare
      congenital heart disease usually diagnosed during childhood. Rarely, some
      patients remain undiagnosed and develop symptoms of heart failure during
      adulthood due to dysfunction of the left ventricle and systemic atrioventricular
      valve. We report on a 69-year-old male patient with a history of percutaneous
      coronary intervention and stent implantation for coronary artery disease and
      coronary artery anomaly, in whom diagnosis of c-TGA was missed.

PMID- 22395380
TI  - [Cardiac pacemakers designed for magnetic resonance environment].
AB  - Electromagnetic fields associated with magnetic resonance imaging (MRI) can cause
      serious functional disturbances in patients with cardiac pacemakers. Thus, an
      implanted pacemaker is generally considered a contraindication for an MRI scan.
      Studies have shown that MRI indication may emerge in about 17% of patients within
      one year of pacemaker implantation, and up to 75% of these patients may require
      MRI during the lifetime of their device. Introduction of pacemaker systems
      designed specifically for the MRI environment is an important development,
      providing pacemaker patients with access to this important diagnostic modality.
      In this article, the current status of MR conditional pacemakers is discussed,
      together with clinical applications.

PMID- 22395381
TI  - Almanac 2011: cardiomyopathies. The national society journals present selected
      research that has driven recent advances in clinical cardiology.
AB  - As we approach the end of 2011 it is clear that the next few years are going to
      be dominated by the application of new high throughput genetic screening
      techniques, capable of screening the entire exome or indeed genome. Understanding
      the data generated by these techniques will require new and equally sophisticated
      analysis of large and complex datasets, using a systems biology approach with
      deeper phenotyping and advanced modelling techniques that have the flexibility
      for continuous update, refinement with discovery of new knowledge. Exciting new
      developments that may also transform cardiomyopathy research include those of
      infrastructure and organisation (multi-centre collaborations) and spin-offs from
      the field of regenerative medicine research. For clinical researchers that
      translate this information to the clinic the focus will however remain the same;
      namely improvement of quality and quantity of life.

PMID- 22395382
TI  - Almanac 2011: valvular heart disease . The national society journals present
      selected research that has driven recent advances in clinical cardiology.

PMID- 22395383
TI  - [Suggestions on how to do: practical tips for transseptal cardiac
      catheterization].

PMID- 22395384
TI  - Coexistence of sinus venosus and ostium primum atrial septal defects.

PMID- 22395385
TI  - Intracardiac fistula in a patient with prosthetic valve endocarditis.

PMID- 22395386
TI  - Two-dimensional strain imaging to predict the localization of an accessory
      pathway.

PMID- 22395387
TI  - Coronary-to-pulmonary artery fistula due to a penetrating trauma.

PMID- 22395388
TI  - [A large atrial septal aneurysm with spontaneous echo contrast].

PMID- 22395390
TI  - [Comment on: Practical tips for the measurement of fractional flow reserve (FFR)
      (Turk Kardiyol Dern Ars 2011;39:433-435)].

PMID- 22395391
TI  - Aerococcus viridans is not a matter of opinion. Comment on: An unusual
      microorganism, Aerococcus viridans, causing endocarditis and aortic valvular
      obstruction due to a huge vegetation (Turk Kardiyol Dern Ars 2011;39:317-319).

PMID- 22395392
TI  - CT features of blunt abdominal aortic injury.
AB  - Abdominal aortic injuries are uncommon following blunt trauma, with relatively
      few reported series in the radiology literature. This study was conducted to
      identify common locations and imaging features of blunt traumatic abdominal
      aortic injury, the presence of associated visceral and osseous injuries, and the
      mechanisms of trauma. A retrospective review of 9,213 trauma registry entries
      over a 7-year period yielded 103 patients with aortic injuries, 12 of which had
      direct signs of abdominal segment involvement (dissection flap, focal intimal
      injury, intramural hematoma, active extravasation of contrast, or pseudoaneurysm
      formation). The majority (75 %) was isolated to the abdomen-67 % of which was
      infrarenal, 33 % suprarenal-while the other 25 % was a contiguous extension from
      a thoracic injury. Abdominal aortic injuries were uncommonly seen in isolation:
      all but one patient (92 %) demonstrated either retroperitoneal blood or
      stranding, hemoperitoneum, and/or CT signs of hypoperfusion complex, and only one
      patient (8 %) had no associated solid organ or skeletal injuries. All patients
      had a mechanism of injury which involved direct trauma to the abdomen, most
      commonly a motor vehicle collision. Similar to other recent series, there was an
      increased rate of abdominal segment injury (11.7 % of all aortic injuries) in
      this series compared to more remote autopsy series. This difference is likely due
      to detection of injuries which went undiagnosed before the widespread use of
      multidetector CT, which has become the standard of care for both acute evaluation
      following blunt trauma and for follow-up.

PMID- 22395402
TI  - Submerged fermentation of the edible mushroom Pleurotus ostreatus in a batch
      stirred tank bioreactor as a promising alternative for the effective production
      of bioactive metabolites.
AB  - The aim of this study was to investigate the potential of the submerged
      fermentation procedure in the production of bioactive metabolites of the common
      edible mushroom Pleurotus ostreatus. The biomass of the mushroom strain was
      produced by submerged fermentation in a batch stirred tank bioreactor and
      extracted by solvents of increasing polarity. The dichloromethane and methanol
      extract were fractioned by different techniques including Adsorption
      Chromatography and Fast Centrifugal Partition Chromatography (FCPC). The
      structures of pure compounds were elucidated with 1D/2D NMR-spectroscopic
      analyses, and chemical correlations combined with GC/MS and LC/MS experiments.
      Nineteen metabolites (e.g., fatty acids, phenolic metabolites, nucleotides and
      alkaloids) were isolated. Beyond the production of known metabolites, we report
      herein the production also of trans-3,4-dihydro-3,4,8-trihydroxynapthalen-1(2H)
      one, indolo-3-carboxylic acid, 3-formylpyrrole and 4-hydroxybenzoic acid, that
      have pharmaceutical interest and are isolated for the first time from Pleurotus
      strains. This work indicates the great potential of the established bioprocess
      for the production of P. ostreatus mycelia with enhanced metabolic profile.

PMID- 22395403
TI  - Phenolic alkaloids from Menispermum dauricum rhizome protect against brain
      ischemia injury via regulation of GLT-1, EAAC1 and ROS generation.
AB  - Menispermum dauricum rhizome has been widely used in China to treat various
      cardiovascular and thrombosis disorders. Some studies have reported that the
      phenolic alkaloids of Menispermum dauricum rhizome (PAM) have protective effects
      against brain ischemia injury, but the mechanism of this action remains to be
      clarified. In the present study, we investigated the possible mechanisms of
      action of PAM on experimental brain ischemia injury. Oxygen and glucose
      deprivation (OGD) in rat primary cortical cultures and middle cerebral artery
      occlusion in rats were used to mimic ischemia-reperfusion injury, respectively.
      The results suggested that PAM protected rat primary cortical cultures against
      OGD-reoxygenation induced cytotoxicity. PAM decreased extracellular glutamate
      content and markedly prevented the effects induced by OGD on protein level of GLT
      1 and EAAC1 glutamate transporters. In addition, it reduced intracellular ROS
      generation. In vivo, PAM significantly reduced cerebral infarct area and
      ameliorated neurological functional deficits at different time points. Our
      findings revealed that the possible mechanism of action of PAM protected against
      brain ischemia injury involves regulation of GLT-1, EAAC1 and ROS generation.

PMID- 22395405
TI  - Synthesis, property characterization and photocatalytic activity of the novel
      composite polymer polyaniline/Bi2SnTiO7.
AB  - A novel polyaniline/Bi(2)SnTiO(7 )composite polymer was synthesized by chemical
      oxidation in-situ polymerization method and sol-gel method for the first time.
      The structural properties of novel polyaniline/Bi(2)SnTiO(7) have been
      characterized by X-ray diffraction, scanning electron microscopy, X-ray
      photoelectron spectroscopy and X-ray spectrometry. The lattice parameter of
      Bi(2)SnTiO(7) was found to be a = 10.52582(8) A. The photocatalytic degradation
      of methylene blue was realized under visible light irradiation with the novel
      polyaniline/Bi(2)SnTiO(7) as catalyst. The results showed that novel
      polyaniline/Bi(2)SnTiO(7 )possessed higher catalytic activity compared with
      Bi(2)InTaO(7) or pure TiO(2) or N-doped TiO(2) for photocatalytic degradation of
      methylene blue under visible light irradiation. The photocatalytic degradation of
      methylene blue with the novel polyaniline/Bi(2)SnTiO(7) or N-doped TiO(2) as
      catalyst followed first-order reaction kinetics, and the first-order rate
      constant was 0.01504 or 0.00333 min(-1). After visible light irradiation for 220
      minutes with novel polyaniline/Bi(2)SnTiO(7 )as catalyst, complete removal and
      mineralization of methylene blue was observed. The reduction of the total organic
      carbon, the formation of inorganic products, SO(4)2- and NO(3-), and the
      evolution of CO(2) revealed the continuous mineralization of methylene blue
      during the photocatalytic process. The possible photocatalytic degradation
      pathway of methylene blue was obtained under visible light irradiation.

PMID- 22395404
TI  - Inhibitory effects of enalaprilat on rat cardiac fibroblast proliferation via
      ROS/P38MAPK/TGF-beta1 signaling pathway.
AB  - Enalaprilat (Ena.), an angiotensin II (Ang II) converting enzyme inhibitor
      (ACEI), can produce some therapeutic effects on hypertension, ventricular
      hypertrophy and myocardial remodeling in clinic, but its precise mechanism,
      especially its signaling pathways remain elusive. In this study, cardiac
      fibroblasts (CFb) was isolated by the trypsin digestion method; a BrdU
      proliferation assay was adopted to determine cell proliferation; an
      immunofluorescence assay was used to measure intracellular reactive oxygen
      species (ROS); immunocytochemistry staining and Western blotting assay were used
      to detect phosphorylated p38 mitogen activated protein kinase (p-p38MAPK) and
      transforming growth factor-beta(1) (TGF-beta(1)) protein expression,
      respectively. The results showed that Ang II (10(-7) M) stimulated the cardiac
      fibroblast proliferation which was inhibited by NAC (an antioxidant), SB203580 (a
      p38MAPK inhibitor) or enalaprilat; Ang II caused an burst of intracellular ROS
      level within thirty minutes, an increase in p-p38MAPK (3.6-fold of that in the
      control group), as well as an elevation of TGF-beta(1) meantime; NAC, an
      antioxidant, and enalaprilat treatment attenuated cardiac fibroblast
      proliferation induced by Ang II and decreased ROS and p-p38MAPK protein levels in
      rat cardiac fibroblast; SB203580 lowered TGF-beta(1) protein expression in rats'
      CFb in a dose-dependent manner. It could be concluded that enalaprilat can
      inhibit the cardiac fibroblast proliferation induced by Ang II via blocking
      ROS/P38MAPK/TGF-beta(1) signaling pathways and the study provides a theoretical
      proof for the application of ACEIs in treating myocardial fibrosis and
      discovering the primary mechanism through which ACEIs inhibit CFb proliferation.

PMID- 22395406
TI  - Separation and identification of highly fluorescent compounds derived from trans
      resveratrol in the leaves of Vitis vinifera infected by Plasmopara viticola.
AB  - A method for identification of highly fluorescent compounds in vine leaves
      infected by Plasmopara viticola was developed using reversed phase liquid
      chromatography with simultaneous diode array and fluorometric detection.
      Fluorescent compounds were extracted from leaves with a methanol-water mixture
      (70:30). Separation by HPLC was performed using a C(18) column and gradient
      elution with water-acetonitrile mixtures (20-80% of acetonitrile). The main
      unknown fluorescent compound was identified by line spectral comparison with a
      standard obtained by UV photoisomerization of trans-resveratrol glucoside, and
      its structure was confirmed by liquid chromatography-mass spectrometry.
      Identification and structural elucidation of the fluorescent compound in the
      leaves of Vitis vinifera allows early detection of Plasmopara viticola invasion.

PMID- 22395407
TI  - Treatment of direct blending dye wastewater and recycling of dye sludge.
AB  - A new sorbent material, barium sulfate-Direct Blending Yellow D-3RNL hybrid
      (BSD), was synthesized and characterized by various methods. Both the anionic
      dyes, Reactive Brilliant Red X-3B and Weak Acid Green GS were hardly adsorbed by
      the BSD material, while the sorption of Ethyl Violet (EV) and Victoria Blue B
      were extremely obvious. The sorption of cationic dyes obeyed the Langmuir
      isotherm model, which depended on the electric charge attraction. The saturation
      amount of EV adsorbed onto the BSD material approached to 39.36 mg/g. The
      sorption of EV changed little with pH from 3 to 12 while it increased with
      increasing levels of electrolyte. A dye wastewater sampled from Jinjiang
      Chemicals was treated, and the color removal rate was more than the COD removal
      rate. In addition, the cationic dye-BSD sludge was utilized as a colorant fill-in
      coating. The light stability and thermal stability of the colorant was measured
      and exhibited good features. This work provided a simple and eco-friendly method
      for dye wastewater treatment with recycling of waste.

PMID- 22395408
TI  - Effects of Pithecellobium jiringa ethanol extract against ethanol-induced gastric
      mucosal injuries in Sprague-Dawley rats.
AB  - Current anti-gastric ulcer agents have side effects, despite the progression and
      expansion of advances in treatment. This study aimed to investigate the
      gastroprotective mechanisms of Pithecellobium jiringa ethanol extract against
      ethanol-induced gastric mucosal ulcers in rats. For this purpose, Sprague Dawley
      rats were randomly divided into five groups: Group 1 (normal control) rats were
      orally administered with vehicle (carboxymethyl cellulose), Group 2 (ulcer
      control) rats were also orally administered with vehicle. Group 3 (positive
      control) rats were orally administered with 20 mg/kg omeprazole, Groups 4 and 5
      (experimental groups) received ethanol extract of Pithecellobium jiringa ethanol
      extract at a concentration of 250 and 500 mg/kg, respectively. Sixty minutes
      later, vehicle was given orally to the normal control group, and absolute ethanol
      was given orally to the ulcer control, positive control and experimental groups
      to generate gastric mucosal injury. The rats were sacrificed an hour later. The
      effect of oral administration of plant extract on ethanol-induced gastric mucosal
      injury was studied grossly and histology. The level of lipid peroxidation
      (malondialdehyde-MDA), superoxide dismutase (SOD) and gastric wall mucus were
      measured from gastric mucosal homogenate. The ulcer control group exhibited
      severe gastric mucosal injury, and this finding was also confirmed by histology
      of gastric mucosa which showed severe damage to the gastric mucosa with edema and
      leucocyte infiltration of the submucosal layer. Pre-treatment with plant extract
      significantly reduced the formation of ethanol-induced gastric lesions, and
      gastric wall mucus was significantly preserved. The study also indicated a
      significant increase in SOD activity in gastric mucosal homogenate, whereas a
      significant decrease in MDA was observed. Acute toxicity tests did not show any
      signs of toxicity and mortality up to 5 g/kg. The ulcer protective effect of this
      plant may possibly be due to its preservation of gastric wall mucus along with
      increased SOD activity and reduction of oxidative stress (MDA). The extract is
      non-toxic, even at relatively high concentrations.

PMID- 22395409
TI  - Efficient synthesis of beta-enaminones and beta-enaminoesters catalyzed by gold
      (I)/silver (I) under solvent-free conditions.
AB  - An efficient method for the synthesis of beta-enaminones and beta-enaminoesters
      using a combination of [(PPh(3))AuCl]/AgOTf as catalyst has been developed. The
      reaction between 1,3-dicarbonyl compounds and primary amines was carried out
      under solvent-free conditions with low catalyst loading in good to excellent
      yields at room temperature.

PMID- 22395410
TI  - TRPV1 activation prevents nonalcoholic fatty liver through UCP2 upregulation in
      mice.
AB  - Nonalcoholic fatty liver is characterized by the fatty deformation and lipid
      deposition of hepatic parenchymal cells that are associated with cardiometabolic
      diseases. In this study, we report the effect of capsaicin on its receptor,
      transient receptor potential vanilloid 1 (TRPV1) cation channel, in preventing
      fatty liver formation. Functional TRPV1 has been detected in hepatocytes and
      liver tissues. TRPV1 activation by capsaicin reduced lipid accumulation and
      triglyceride level in the liver from wild-type (WT) mice. However, these effects
      were absent in the liver from TRPV1(-/-) mice. Chronic dietary capsaicin
      increased the hepatic uncoupling protein 2 (UCP2) expression in WT but not in
      TRPV1(-/-) mice (P < 0.01). We conclude that TRPV1 long-time activation might
      prevent high-fat diet-induced fatty liver in mice through upregulation of hepatic
      UCP2. Dietary capsaicin may represent a promising intervention in populations at
      high risk for fatty liver.

PMID- 22395412
TI  - Unexpected formation of the nickel seco-tribenzoporphyrazine with a
      tribenzotetraazachlorin-type absorption spectrum.
AB  - Minor products in the reaction between substituted 1,3-diiminoisoindolines and
      2,5-diamino-3,4-dicyanothiophene were identified as the nickel seco
      tribenzoporphyrazines 4 and 5, which have been characterized by UV-vis, MCD, NMR,
      and mass spectroscopy. Experimentally observed tetraazachlorin-type UV-vis
      spectra of new seco-tribenzoporphyrazines were explained on the basis of DFT and
      TDDFT calculations.

PMID- 22395411
TI  - Special features of mitochondrial Ca2+ signalling in adrenal glomerulosa cells.
AB  - Aldosterone, secreted by adrenal glomerulosa cells, allows the adaptation of the
      vertebrate organism to a wide range of physiological and pathological stimuli
      including acute haemodynamic challenges and long-term changes in dietary sodium
      and potassium intake. Most of the extracellular signals are mediated by cytosolic
      Ca2+ signal deriving from Ca2+ release, store-operated and/or voltage-gated Ca2+
      influx. Mitochondria in glomerulosa cells play a fundamental role in generating
      and modulating the final biological response. These organelles not only house
      several enzymes of aldosterone biosynthesis but also-in a Ca2+-dependent manner
      provide NADPH for the function of these enzymes. Moreover, mitochondria,
      constituting a high portion of cytoplasmic volume and displaying a uniquely low
      threshold Ca2+ sequestering ability, shape and thus modulate the decoding of the
      complex cytosolic Ca2+ response. The unusual features of mitochondrial Ca2+
      signalling that permit such an integrative function in adrenal glomerulosa cells
      are hereby described.

PMID- 22395413
TI  - Anatomical study and clinical relevance of the flexor superficialis synovial
      flap: an assessment of 31 hand dissections.
AB  - PURPOSE: The authors present an anatomical study of the flexor digitorum
      superficialis synovial flap and its clinical application for palmar soft tissue
      defects in hand trauma. METHODS: Green latex was injected into the brachial
      artery of thirty-one human upper limbs from corpses donated to science.
      Anatomical features of this pedicled flap were assessed: arterial
      vascularization, dimensions and covering surface. RESULTS: The anatomical support
      of this flap is the synovial tissue of the flexor tendons, and particularly the
      superficial layer of the synovial system, covering the flexor digitorum
      superficialis (FDS) tendons in the forearm. It is vascularized by four different
      arteries: a constant collateral branch of the ulnar artery, and three inconstant
      arterial supports: from collateral branches of the superficial palmar arch, from
      the radial artery, and from the vasa nervorum of the median nerve. The flap is
      harvested from proximal to distal on the ulnar pedicle to cover the palmar soft
      tissue defects of the hand. A clinical application of this synovial flap is
      presented via a case report for covering a palmar skin defect secondary to a hand
      injury. CONCLUSIONS: The synovial flap contains a constant ulnar pedicle and
      could be considered a useful alternative to cover palmar soft tissue defects.

PMID- 22395414
TI  - Reactions of triflate esters and triflamides with an organic neutral super
      electron-donor.
AB  - The bis-pyridinylidene 13 converts aliphatic and aryl triflate esters to the
      corresponding alcohols and phenols respectively, using DMF as solvent, generally
      in excellent yields. While the deprotection of aryl triflates has been seen with
      other reagents and by more than one mechanism, the deprotection of alkyl
      triflates is a new reaction. Studies with (18)O labelled DMF indicate that the C
      O bond stays intact and hence it is the S-O bond that cleaves, underlining that
      the cleavage results from the extraordinary electron donor capability of 13.
      Trifluoromethanesulfonamides are converted to the parent amines in like manner,
      representing the first cleavage of such substrates by a ground-state organic
      reducing reagent.

PMID- 22395416
TI  - The metastasis suppressor KISS1 lacks antimetastatic activity in the C8161.9
      xenograft model of melanoma.
AB  - The objective of this study was to use the established xenograft model of human
      melanoma (C8161.9) to test a pharmacological approach to the effect of the
      metastasis suppressor KISS1. A KISS1 analog was used to inhibit the metastatic
      development of C8161.9 cells in nude mice. Further experiments were performed to
      test the validity of the C8161.9 model and test the connection between KISS1
      expression and loss of metastatic potential. New clones of C8161.9 cells were
      obtained, with or without KISS1 expression, and were tested for metastasis
      formation. The absence of benefit in survival with the KISS1 analog compared with
      PBS prompted us to revisit the C8161.9 model. We found that the cells expressing
      KISS1, used in the previous study and obtained by transfection and single-cell
      cloning, were defective for both formation of orthotopic tumors and metastases.
      In mixing experiments, these cells could not suppress orthotopic tumor growth of
      KISS1-negative C8161.9 cells, suggesting that the suppression of metastasis by
      C8161.9-KISS1 cells may be intrinsic to the selected clone rather than related to
      KISS1 expression. Isolation of clones from parental C8161.9 cells in soft agar
      yielded cell populations that phenotypically and genotypically mimicked the KISS1
      positive clone. In addition, new clones expressing KISS1 did not show any
      decrease in metastatic growth. These data demonstrate the heterogeneity of cell
      types in the C8161.9 cell line and the high risk of artifact linked to single
      cell selection. A different xenograft model will be necessary to evaluate the use
      of KISS1 analogs as antimetastatic therapy.

PMID- 22395417
TI  - The dermoscopic variability of pigment network in melanoma in situ.
AB  - To define the dermoscopic aspects of the network in melanoma in situ (MIS), using
      both standard and newly introduced network descriptors. Fifty-four histologically
      confirmed MIS with a reticular pattern, 108 atypical reticular naevi and 108
      typical reticular naevi were evaluated for the presence of 11 network
      descriptors. The ABCD-score and the seven-point score were calculated, and the
      diameter of the lesions was measured by means of a dedicated software. Clinical
      data including age, sex and skin site were also considered. The prevalence of
      different dermoscopic features was calculated to allow (i) the identification of
      lesions to be excised and (ii) the distinction between MIS and dermoscopically
      atypical naevi. In dermoscopically atypical lesions (MIS and atypical naevi), the
      frequency of all descriptors significantly differed from those of typical naevi.
      With respect to atypical naevi, MIS more frequently showed larger size, an
      atypical network involving more than half of the lesion, the contemporary
      presence of more than one type of network and more extended reticular grey-blue
      regression areas located both in the centre and at the periphery of the lesion.
      The list of network descriptors proposed by us can be used for the identification
      of lesions that should be subjected to surgery. For the distinction between MIS
      and atypical naevi, the extension of an atypical network, the presence of more
      than one type of network, the distribution of reticular grey-blue areas and the
      lesion diameter must be considered.

PMID- 22395415
TI  - A brief history of melanoma:  from mummies to mutations.
AB  - In recent years, melanoma research has undergone a renaissance. What was once
      viewed, at least in the metastatic setting, as an intractable and untreatable
      disease is now revealing its molecular weaknesses. 2011 was a landmark year for
      melanoma therapy, with two new agents, the anti-CTLA4 antibody ipilimumab and the
      BRAF inhibitor vemurafenib, shown to confer a survival benefit in randomized
      phase III clinical trials. Overlooked in the recent flurry of interest that has
      accompanied the development of these drugs, melanoma is in fact an ancient
      disease that has long frustrated attempts at therapeutic interventions. In this
      article, we trace the history of melanoma: from the earliest known cases of
      melanoma in pre-Colombian South America, through the explorations of the
      Victorian anatomists right up to the molecular biology revolution of the 20th
      century that allowed for the identification of the key driving events required
      for melanomagenesis. We further outline how observations about melanoma
      heterogeneity, first made over 190 years ago, continue to drive our efforts to
      reduce melanoma to the level of a chronic, manageable disease and ultimately to
      cure it entirely.

PMID- 22395418
TI  - Reducing patient burden to the FACT-Melanoma quality-of-life questionnaire.
AB  - Respondent burden has been defined as the cumulative demand placed on study
      participants related to the use of questionnaires or measurement instruments. The
      aim of this study was to reduce respondent burden associated with the Functional
      Assessment of Cancer Therapy-Melanoma (FACT-M), a melanoma-specific quality-of
      life questionnaire, through item reduction using multiple psychometric
      approaches. Data for this study were pooled from three institutional review board
      approved protocols. Poorly performing items were identified through
      distributional and correlation analyses, confirmatory factor analysis,
      reliability estimation, and Rasch-based approaches in a developmental dataset,
      and the reduced scale was assessed in a separate testing cohort. Validity,
      reliability, goodness of fit, and Rasch-based testing were carried out for both
      the full and the reduced scales. The clinical characteristics of the development
      (n=198) and testing (n=204) cohorts were similar. Three items identified through
      classical psychometric approaches and three items identified by Rasch-based
      analyses were excluded from the FACT-M subscale. Two additional items were
      identified for potential reduction but were ultimately maintained due to the
      adverse consequences to the psychometric integrity of the reduced instrument. The
      reduced FACT-M module contains 18 items. In addition to psychometric assessment,
      expert consultation was essential when examining areas of content redundancy and
      was critical when considering specific items for removal. This methodological
      approach reduced respondent burden by 25% while maintaining the psychometric
      integrity of the FACT-M.

PMID- 22395420
TI  - Electrochemistry-enabled fabrication of orthogonal nanotopography and surface
      chemistry gradients for high-throughput screening.
AB  - Gradient surfaces are emerging tools for investigating mammalian cell-surface
      interactions in high throughput. We demonstrate the electrochemical fabrication
      of an orthogonal gradient platform combining a porous silicon (pSi) pore size
      gradient with an orthogonal gradient of peptide ligand density. pSi gradients
      were fabricated via the anodic etching of a silicon wafer with pore sizes ranging
      from hundreds to tens of nanometers. A chemical gradient of ethyl-6
      bromohexanoate was generated orthogonally to the pSi gradient via electrochemical
      attachment. Subsequent hydrolysis and activation of the chemical gradient allowed
      for the generation of a cyclic RGD gradient. Whilst mesenchymal stem cells (MSC)
      were shown to respond to both the topographical and chemical cues arising from
      the orthogonal gradient, the MSC's responded more strongly to changes in RGD
      density than to changes in pore size during short-term culture.

PMID- 22395421
TI  - CCR7 deficiency causes diarrhea associated with altered ion transport in
      colonocytes in the absence of overt colitis.
AB  - The chemokine receptor CCR7 is a central regulator in the maintenance of cellular
      homeostasis of mucosal tissues. CCR7-/- mice develop autoimmune gastritis and
      exocrinopathy accompanied by the formation of mucosal tertiary lymphoid
      follicles. Here we found that CCR7-deficient mice frequently suffered from
      chronic diarrhea linked with increased gastrointestinal motility and the
      development of severe anorectal prolapse. Enhanced formation of intestinal
      lymphoid follicles was associated with an elevated proportion of activated
      colonic T cells and increased production of the cytokine interleukin (IL)-1beta.
      To uncover the pathomechanisms of diarrhea in CCR7-/- mice, colonic epithelial
      barrier and ion channel activities were analyzed in Ussing chambers. Although
      overt acute colitis was absent, CCR7 deficiency resulted in reduced electrogenic
      sodium absorption and colonic chloride secretion. As it is known that IL-1beta
      regulates epithelial sodium channel (ENaC) activity, these data imply a causal
      link between CCR7 expression, IL-1beta level, and Na+ malabsorption owing to
      altered ENaC expression and diarrhea.

PMID- 22395422
TI  - Mechanical testing of mouse carotid arteries: from newborn to adult.
AB  - The large conducting arteries in vertebrates are composed of a specialized
      extracellular matrix designed to provide pulse dampening and reduce the work
      performed by the heart. The mix of matrix proteins determines the passive
      mechanical properties of the arterial wall(1). When the matrix proteins are
      altered in development, aging, disease or injury, the arterial wall remodels,
      changing the mechanical properties and leading to subsequent cardiac
      adaptation(2). In normal development, the remodeling leads to a functional
      cardiac and cardiovascular system optimized for the needs of the adult organism.
      In disease, the remodeling often leads to a negative feedback cycle that can
      cause cardiac failure and death. By quantifying passive arterial mechanical
      properties in development and disease, we can begin to understand the normal
      remodeling process to recreate it in tissue engineering and the pathological
      remodeling process to test disease treatments.     Mice are useful models for
      studying passive arterial mechanics in development and disease. They have a
      relatively short lifespan (mature adults by 3 months and aged adults by 2 years),
      so developmental(3) and aging studies(4) can be carried out over a limited time
      course. The advances in mouse genetics provide numerous genotypes and phenotypes
      to study changes in arterial mechanics with disease progression(5) and disease
      treatment(6). Mice can also be manipulated experimentally to study the effects of
      changes in hemodynamic parameters on the arterial remodeling process(7). One
      drawback of the mouse model, especially for examining young ages, is the size of
      the arteries. We describe a method for passive mechanical testing of carotid
      arteries from mice aged 3 days to adult (approximately 90 days). We adapt a
      commercial myograph system to mount the arteries and perform multiple pressure or
      axial stretch protocols on each specimen. We discuss suitable protocols for each
      age, the necessary measurements and provide example data. We also include data
      analysis strategies for rigorous mechanical characterization of the arteries.

PMID- 22395423
TI  - Synthesis and structural characterisation of (aryl-BIAN)copper(I) complexes and
      their application as catalysts for the cycloaddition of azides and alkynes.
AB  - A series of Ar-BIAN-based copper(I) complexes (where Ar-BIAN =
      bis(aryl)acenaphthenequinonediimine) were synthesised and characterised by (1)H
      and (13)C NMR spectroscopies, FT-IR spectroscopy, MALDI-TOF-MS spectrometry,
      cyclic voltammetry and single crystal X-ray diffraction. The bis-chelated
      complexes of general formula [Cu(Ar-BIAN)(2)]BF(4) (where Ar = C(6)H(5) (1), 4
      iPrC(6)H(4) (3), 2-iPrC(6)H(4) (4)) were prepared by reaction of
      [Cu(NCMe)(4)]BF(4) with two equivalents of the corresponding Ar-BIAN ligands, in
      dichloromethane, while the mono-chelated complexes of the type [Cu(Ar
      BIAN)L(2)]BF(4) (where Ar = 2,6-iPr(2)C(6)H(3), L = PhCN (6); Ar = 4-iPrC(6)H(4),
      L = PPh(3) (7)) were readily accessible by treatment of [Cu(NCR)(4)]BF(4) (R =
      Me, Ph) with one equivalent of the corresponding Ar-BIAN ligands in the absence
      or presence of two equivalents of PPh(3), in the same solvent. The structures of
      complexes 3, 4, 6 and 7 were obtained by single crystal X-ray diffraction,
      showing distorted tetrahedral geometries around the copper centres in all cases.
      The electrochemical studies of these complexes and of the already reported
      [Cu(2,4,6-Me(3)C(6)H(2)-BIAN)(2)]BF(4) (2) and [Cu(2,6-iPr(2)C(6)H(3)
      BIAN)(NCMe)(2)] (5), demonstrated that the bis-chelated complexes 1-4 undergo a
      reversible one-electron reduction or oxidation processes on copper, while the
      mono-chelated complexes 5-7 show a partially reversible oxidation and an
      irreversible reduction feature. Both kinds of (Ar-BIAN)copper(I) complexes are
      active catalysts for the copper(I)-catalysed azide-alkyne cycloaddition reaction
      (CuAAC). Complex 7, bearing PPh(3) ligands, exhibits the highest catalytic
      activity, which is comparable with that of the typical CuSO(4)-sodium ascorbate
      catalyst system.

PMID- 22395424
TI  - Effects of embryonic exposure to polychlorinated biphenyls on zebrafish skeletal
      development.
AB  - Polychlorinated biphenyls (PCBs) are persistent organic pollutants that affect
      embryonic development. The purpose of this study was to examine the effects of
      embryonic exposure to PCBs on early skeletal development in zebrafish (Danio
      rerio). Zebrafish embryos were immediately exposed to various concentrations (0,
      0.125, 0.25, 0.5 and 1.0 mg/l) of PCBs (Aroclor 1254) after fertilization.
      Embryos were assessed at 24, 48, 72, 96 and 120 h post-fertilization (hpf) for
      changes in embryonic survival and malformation rates. Calcium content and vitamin
      D receptor (VDR), parathyroid hormone (PTH) and TRVP6 mRNA expressions were
      assessed at 120 hpf. The results showed that PCBs exposure decreased the survival
      rate of the embryos in a time-and dose-dependent manner. The embryos exposed to
      the higher concentrations of PCBs (0.5 and 1.0 mg/l) displayed obvious skeletal
      morphological deformities. At 120 hpf, the calcium content of the zebrafish was
      downregulated in all the PCB-treated groups. VDR, PTH and TRVP6 mRNA expressions
      were all affected by PCBs. By 120 hpf, the mRNA expressions of VDR, PTH and TRVP6
      from the PCB-treated larvae were all upregulated. The expressions of PTH and
      TRVP6 positively correlated with the level of PCBs to which the embryos were
      exposed. These results suggest that embryonic exposure to PCBs induces
      developmental deficits in the zebrafish skeleton.

PMID- 22395425
TI  - Cortisol awakening response and pain-related fear-avoidance versus endurance in
      patients six months after lumbar disc surgery.
AB  - Recent research indicates that stress-induced, prolonged deviations in basal
      adrenocortical activity might contribute to ongoing/recurrent pain following
      lumbar disc surgery. Further, fear-avoidance and endurance responses to pain (FAR
      and ER) are regarded as important risk factors for pain after surgery. In
      patients with non-specific low back pain, FAR appear to possibly increase pain
      related arousal, whereas ER may have an arousal-lowering effect, indicated by
      adrenocortical activity. The current study explores the relationship between
      basal adrenocortical activity and FAR and ER. Thirty-six patients 6 months after
      lumbar disc surgery participated. Basal adrenocortical activity was assessed
      through the cortisol awakening response (CAR), using salivary samples collected
      on two consecutive days. FAR and ER were estimated using questionnaires. While
      the ER variables pain-persistence behavior and positive mood despite pain showed
      negative associations with the CAR, the FAR variables fear-avoidance beliefs and
      avoidance of social activity were positively correlated with it. Additionally,
      higher CAR levels were found in patients with high versus patients with low fear
      avoidance beliefs and, conversely, in patients with low versus high positive mood
      and pain persistence. These results indicate that FAR may increase the
      individuals' level of pain-related stress among patients after disc surgery,
      while ER may lower it.

PMID- 22395426
TI  - Content validity and inter-rater reliability of the Halliwick-concept-based
      instrument 'Swimming with Independent Measure'.
AB  - The Halliwick concept is widely used in different settings to promote joyful
      movement in water and swimming. To assess the swimming skills and progression of
      an individual swimmer, a valid and reliable measure should be used. The Halliwick
      concept-based Swimming with Independent Measure (SWIM) was introduced for this
      purpose. We aimed to determine its content validity and inter-rater reliability.
      Fifty-four healthy children, 3.5-11 years old, from a mainstream swimming program
      participated in a content validity study. They were evaluated with SWIM and the
      national evaluation system of swimming abilities (classifying children into seven
      categories). To study the inter-rater reliability of SWIM, we included 37
      children and youth from a Halliwick swimming program, aged 7-22 years, who were
      evaluated by two Halliwick instructors independently. The average SWIM score
      differed between national evaluation system categories and followed the expected
      order (P<0.001), whereby a ceiling effect was observed in the higher categories.
      High inter-rater reliability was found for all 11 SWIM items. The lowest
      reliability was observed for item G (sagittal rotation), although the estimates
      were still above 0.9. As expected, the highest reliability was observed for the
      total score (intraclass correlation 0.996). The validity of SWIM with respect to
      the national evaluation system of swimming abilities is high until the point
      where a swimmer is well adapted to water and already able to learn some swimming
      techniques. The inter-rater reliability of SWIM is very high; thus, we believe
      that SWIM can be used in further research and practice to follow the progress of
      swimmers.

PMID- 22395427
TI  - Optical classification of algae species with a glass lab-on-a-chip.
AB  - The identification of submillimetre phytoplankton is important for monitoring
      environmental and climate changes, as well as evaluating water for health
      reasons. Current standard methods for phytoplankton species identification
      require sample collection and ex situ analysis, an expensive procedure which
      prevents the rapid identification of phytoplankton outbreaks. To address this, we
      use a glass-based microchip with a microchannel and waveguide included on a
      monolithic substrate, and demonstrate its use for identifying phytoplankton
      species. The microchannel and the specimens inside it are illuminated by laser
      light from the curved waveguide as algae-laden water is passed through the
      channel. The intensity distribution of the light collected from the biochip is
      monitored with an external photodetector. Here, we demonstrate that the
      characteristics of the photodiode signal from this simple and robust system can
      provide significant and useful information as to the contents of the channel.
      Specifically, we show first that the signals are correlated to the size of algae
      cells. Using a pattern-matching neural network, we demonstrate the successful
      classification of five algae species with an average 78% positive identification
      rate. Furthermore, as a proof-of-concept for field-operation, we show that the
      chip can be used to distinguish between detritus in field-collected water and the
      toxin-producing cyanobacterium Cyanothece.

PMID- 22395428
TI  - Behavioral characterization of escalated aggression induced by GABA(B) receptor
      activation in the dorsal raphe nucleus.
AB  - RATIONALE: Pharmacological activation of GABA(B) receptors in the dorsal raphe
      nucleus (DRN) can escalate territorial aggression in male mice. OBJECTIVES: We
      characterized this escalated aggression in terms of its behavioral and
      environmental determinants. METHODS: Aggressive behavior of resident male (CFW or
      ICR mouse) was assessed in confrontations with a group-housed intruder. Either
      baclofen (0.06 nmol/0.2 MUl) or vehicle (saline) was microinjected into the DRN
      10 min before the confrontation. We examined baclofen-heightened aggression in
      five situations: aggression in a neutral arena and after social instigation
      (experiment 1), aggression during the light phase of the cycle (experiment 2),
      aggression without prior fighting experience (experiment 3), aggression toward a
      female (experiment 4), and aggression after defeat experiences (experiment 5). In
      addition, we examined the body targets towards which bites are directed and the
      duration of aggressive bursts after baclofen treatment. RESULTS: Regardless of
      the past social experience, baclofen escalated aggressive behaviors. Even in the
      neutral arena and after defeat experiences, where aggressive behaviors were
      inhibited, baclofen significantly increased aggression. Baclofen increased attack
      bites directed at vulnerable body areas of male intruders but not toward a female
      and only in the dark. Also, baclofen prolonged the duration of aggressive bursts.
      CONCLUSIONS: For baclofen to escalate aggression, specific stimulation (male
      intruder) and tonic level of serotonin (dark cycle) are required. Once aggressive
      behavior is triggered, intra-DRN baclofen escalates the level of aggression to
      abnormal levels and renders it difficult to terminate. Also, baclofen counteracts
      the effects of novelty or past experiences of defeat.

PMID- 22395429
TI  - Antidepressants and lethal violence in the Netherlands 1994-2008.
AB  - RATIONALE: There is an ongoing discussion on the relation between risk of violent
      behaviour and the use of antidepressants. The claim that the use of
      antidepressants can cause violent behaviour would gain credibility if a positive
      association between the two could be established. OBJECTIVE: The objective of
      this study is to evaluate the relationship between homicide, suicide and homicide
      suicide rates and the rates of antidepressant use by gender and age group.
      METHOD: Nationwide data from the Netherlands on antidepressant prescriptions
      (ADs, SSRI and venlafaxine) and lethal violence were analysed over the 15-year
      period from 1994 to 2008. RESULTS: The findings indicated a significant negative
      association between lethal violence (homicide and suicide) and prescription of
      antidepressants in the Netherlands, indicating that in a period in which the
      exposure of the Dutch population to antidepressants increased, rates of lethal
      violence decreased. CONCLUSIONS: These data lend no support for an important role
      of antidepressant use in lethal violence.

PMID- 22395431
TI  - Intradural spinal metastases: a surgical series of 15 patients.
AB  - BACKGROUND: Intradural spinal metastases are rare, and little is known regarding
      surgical indications and outcomes. METHODS: A retrospective search identified
      adults with intradural spinal metastases operated on at the Mayo Clinic from 1994
      2011. Data were collected regarding demographics, tumor type and location, and
      outcomes. RESULTS: Fifteen patients with intradural spinal metastases were
      investigated. The age range was 38-74 years (mean = 55 years; +/-SD = 11.1).
      Predominant tumor location and type were lumbosacral and adenocarcinoma,
      respectively: 3 intramedullary and 12 extramedullary. Patients were operated on
      to relieve or prevent progressive/intractable neurological sequelae and/or pain.
      Of 13 who underwent resection, gross total removal was reported in 10; simple
      biopsy was performed in 2. There was one surgical complication, no medical
      complications, and no surgical mortality. At median follow-up of 1 month
      postoperatively, 10 of 15 patients were stable or improved. Of 13 patients who
      underwent resection, 10 were stable or improved. Of two patients who underwent
      biopsy, neither was stable or improved at follow-up. Using the Modified McCormick
      Scale, 11 of 15 patients were "functional" preoperatively and 4 went from
      "functional" preoperatively to "non-functional" postoperatively. Three of those
      four died within 60 days of surgery from systemic disease progression. Median
      hospital stay was 8 days. Ten of 15 patients died by the end of the study period,
      and the median survival of 15 patients was 5 months. CONCLUSIONS: With improved
      outcomes in metastatic cancer, more patients are encountered in practice. An
      aggressive surgical approach is warranted for extramedullary lesions, whereas
      caution is advised for intramedullary lesions. Postoperative functional decline
      is more likely due to systemic disease progression rather than surgery.

PMID- 22395430
TI  - Altered cerebral blood flow and neurocognitive correlates in adolescent cannabis
      users.
AB  - RATIONALE: The effects of adolescent marijuana use on the developing brain remain
      unclear, despite its prevalence. Arterial spin labeling (ASL) is a noninvasive
      imaging technique that characterizes neurovascular status and cerebral blood flow
      (CBF), potentially revealing contributors to neuropathological alterations. No
      studies to date have looked at CBF in adolescent marijuana users. OBJECTIVES:
      This study examined CBF in adolescent marijuana users and matched healthy
      controls at baseline and after 4 weeks of monitored abstinence. METHODS: Heavy
      adolescent marijuana users (n = 23, >200 lifetime marijuana use days) and
      demographically matched controls (n = 23) with limited substance exposure
      underwent an ASL brain scan at an initial session and after 4 weeks of sequential
      urine toxicology to confirm abstinence. RESULTS: Marijuana users showed reduced
      CBF in four cortical regions including the left superior and middle temporal
      gyri, left insula, left and right medial frontal gyrus, and left supramarginal
      gyrus at baseline; users showed increased CBF in the right precuneus at baseline,
      as compared to controls (corrected p values < 0.05). No between group differences
      were found at follow-up. CONCLUSIONS: Marijuana use may influence CBF in
      otherwise healthy adolescents acutely; however, group differences were not
      observed after several weeks of abstinence. Neurovascular alterations may
      contribute to or underlie changes in brain activation, neuropsychological
      performance, and mood observed in young cannabis users with less than a month of
      abstinence.

PMID- 22395433
TI  - Strength testing of the human olfactory nerve at the frontal skull base.
AB  - Olfactory dysfunction may influence the quality of life tremendously. This study
      investigated the strength of the human olfactory nerve at the frontal skull base
      using cadavers. A total of 180 olfactory nerves were examined in 90 human
      cadaveric heads. The cut edges of the olfactory nerves were pulled until they
      were pulled out from the skull base. In the first set of 30 cases, each right
      olfactory nerve was pulled 0 degrees  laterally and 0 degrees  upward, and each
      left olfactory nerve was pulled 0 degrees  laterally and 15 degrees  upward. In
      the second set of 30 cases, each right olfactory nerve was pulled 0 degrees 
      laterally and 15 degrees  upward, and each left olfactory nerve was pulled 15
      degrees  laterally and 15 degrees  upward. In the third set of 30 cases, each
      right olfactory nerve was pulled 15 degrees  laterally and 15 degrees  upward,
      and each left olfactory nerve was pulled 30 degrees  laterally and 15 degrees 
      upward. The strength of the olfactory nerve was measured when pulled in each
      direction. There was no significant difference in the strength of the olfactory
      nerves when pulling them in the postero-upward direction between 0 degrees  and
      15 degrees  upward. The strengths of the olfactory nerves when pulling them in
      the postero-lateral direction 0 degrees  and 15 degrees  laterally were 3.14+/
      1.87 and 4.05+/-1.70 g (mean +/- standard deviation [SD]), respectively; the
      difference was almost significant. The olfactory nerve could be pulled more
      laterally than posteriorly because the retraction force is absorbed by the
      lateral wall of the olfactory fossa.

PMID- 22395432
TI  - Mitochondrial metabolism in cancer metastasis: visualizing tumor cell
      mitochondria and the "reverse Warburg effect" in positive lymph node tissue.
AB  - We have recently proposed a new two-compartment model for understanding the
      Warburg effect in tumor metabolism. In this model, glycolytic stromal cells
      produce mitochondrial fuels (L-lactate and ketone bodies) that are then
      transferred to oxidative epithelial cancer cells, driving OXPHOS and
      mitochondrial metabolism. Thus, stromal catabolism fuels anabolic tumor growth
      via energy transfer. We have termed this new cancer paradigm the "reverse Warburg
      effect," because stromal cells undergo aerobic glycolysis, rather than tumor
      cells. To assess whether this mechanism also applies during cancer cell
      metastasis, we analyzed the bioenergetic status of breast cancer lymph node
      metastases, by employing a series of metabolic protein markers. For this purpose,
      we used MCT4 to identify glycolytic cells. Similarly, we used TO MM20 and COX
      staining as markers of mitochondrial mass and OXPHOS activity, respectively.
      Consistent with the "reverse Warburg effect," our results indicate that
      metastatic breast cancer cells amplify oxidative mitochondrial metabolism
      (OXPHOS) and that adjacent stromal cells are glycolytic and lack detectable
      mitochondria. Glycolytic stromal cells included cancer-associated fibroblasts,
      adipocytes and inflammatory cells. Double labeling experiments with glycolytic
      (MCT4) and oxidative (TO MM20 or COX) markers directly shows that at least two
      different metabolic compartments co-exist, side-by-side, within primary tumors
      and their metastases. Since cancer-associated immune cells appeared glycolytic,
      this observation may also explain how inflammation literally "fuels" tumor
      progression and metastatic dissemination, by "feeding" mitochondrial metabolism
      in cancer cells. Finally, MCT4(+) and TO MM20(-) "glycolytic" cancer cells were
      rarely observed, indicating that the conventional "Warburg effect" does not
      frequently occur in cancer-positive lymph node metastases.

PMID- 22395434
TI  - Gamma knife radiosurgery for jugular foramen schwannomas.
AB  - Jugular foramen schwannomas are very rare tumors. Advances in skull base surgery
      have led to more aggressive resection of these tumors, but surgery may associate
      with development of new neurological deficits. In this report, we analyze the
      long-term results for 17 patients with newly diagnosed or residual/recurrent
      jugular foramen schwannoma who underwent gamma-knife treatment. During a mean 64
      months of follow-up, magnetic resonance imaging revealed reduced tumor size in 13
      cases and no size change in four cases. The tumor growth control rate was 100%
      and only one patient had transient hoarseness. For patients who have small- to
      moderate-sized jugular foramen schwannomas, gamma-knife radiosurgery is
      associated with good tumor control and carries minimal risk of adverse radiation
      effects.

PMID- 22395436
TI  - Donor age and long-term culture affect differentiation and proliferation of human
      bone marrow mesenchymal stem cells.
AB  - Bone marrow-derived human mesenchymal stem cells (BM-hMSCs) represent a promising
      cell-based therapy for a number of degenerative conditions. Many applications
      require cell expansion and involve the treatment of diseases and conditions found
      in an aging population. Therefore, the effects of donor age and long-term passage
      must be clarified. In this study, the effects of donor age and long-term passage
      on the morphology, proliferation potential, characteristics, mesodermal
      differentiation ability, and transdifferentiation potential of hMSCs towards
      neurogenic lineage were evaluated. Cells from child donors (0-12 years, n = 6)
      maintained their fibroblast-like morphology up to higher passages and
      proliferated in a greater number than those from adult (25-50 years, n = 6) and
      old (over 60 years, n = 6) donors. Adipogenic, osteogenic, and neurogenic
      differentiation potential decreased with age, while chondrogenic potential did
      not change. Long-term passage affected the morphology and proliferation of hMSCs
      from all ages. With increasing passage number, proliferation rate decreased and
      cells lost their typical morphology. Expression levels of neural markers (beta
      III tubulin and NSE) and topo II isoforms in populations of nondifferentiated
      hMSCs were investigated by reverse transcription polymerase chain reaction
      analysis. While neural marker and topo IIbeta expression levels increased due to
      increasing passage number in adult hMSCs compared to child hMSCs, topo IIalpha
      decreased in both. These results indicated that, even under highly standardized
      culture conditions, donor age and long-term passage have effects on hMSC
      characteristics, which should be taken into account prior to stem cell-based
      therapies.

PMID- 22395437
TI  - Concomitant plasmacytoma and B cell lymphoma with discordant light chain
      expression but clonal identity.

PMID- 22395439
TI  - Pathophysiology of ventilator-associated lung injury.
AB  - PURPOSE OF REVIEW: Mechanical ventilation is essential for the support of
      critically ill patients, but may aggravate lung damage, leading to ventilator
      associated lung injury (VALI). VALI results from a succession of events beginning
      with mechanical alteration of lung parenchyma, because of disproportionate stress
      and strain. The resulting structural tension initiates a biological inflammatory
      cascade; however, tension can reach the limits of stress, triggering the
      destruction of structures. This article reviews and discusses the ongoing
      research into the mechanisms of VALI and their implications for the management of
      ventilated patients. RECENT FINDINGS: Several experimental and clinical studies
      have been performed to evaluate the contribution of pathogenic mechanical forces
      to organ and cellular deformation and the implications for guiding ventilator
      management in patients at risk for VALI. VALI may be attenuated by reducing tidal
      volume, but the key variable in determining pulmonary overdistension is
      transpulmonary pressure. Other parameters associated with the induction of VALI
      include positive end-expiratory pressure, inspiratory airflow and time, and
      respiratory frequency. SUMMARY: How ventilation strategy, specific mechanisms of
      mechanotransduction, and their individual threshold values impact on VALI remains
      to be elucidated. In addition, clinical studies are required to evaluate the
      usefulness of individualized ventilator strategies based on lung mechanics.

PMID- 22395438
TI  - Chloroplast movement behavior varies widely among species and does not correlate
      with high light stress tolerance.
AB  - It is well known that chloroplasts move in response to changes in blue light
      intensity in order to optimize light interception, however, little is known about
      interspecific variation and the relative importance of this mechanism for the
      high light stress tolerance of plants. We characterized chloroplast movement
      behavior as changes in light transmission through a leaf in a variety of species
      ranging from ferns to monocots and eudicots and found a wide spectrum of
      responses. Most species exhibited a distinct accumulation response compared to
      the dark positioning, and all species showed a distinct avoidance response. The
      speed with which transmission values changed during the avoidance response was
      consistently faster than that during the accumulation response and speeds varied
      greatly between species. Plants thriving in higher growth light intensities
      showed greater degrees of accumulation responses and faster changes in
      transmission than those that prefer lower light intensities. In some species, the
      chloroplasts on both the adaxial and abaxial leaf surfaces changed their
      positioning in response to light, while in other species only the chloroplasts on
      one leaf side responded. No correlation was found between high light stress
      tolerance and the speed or degree of transmission changes, indicating that plants
      can compensate for slow and limited transmission changes using other
      photoprotective mechanisms.

PMID- 22395440
TI  - Lung imaging for titration of mechanical ventilation.
AB  - PURPOSE OF REVIEW: Computed tomography (CT) has fostered pivotal advancements in
      the understanding of acute lung injury/acute respiratory distress syndrome and
      ventilator-induced lung injury. Apart from CT-based studies, the past years have
      seen fascinating work using positron emission tomography, electrical impedance
      tomography and lung ultrasound as diagnostic tools to optimize mechanical
      ventilation. This review aims to present the major findings of recent studies on
      lung imaging. RECENT FINDINGS: Patients presenting with a focal loss of aeration
      on CT may not be suitable candidates for recruitment maneuvers and high levels of
      positive end-expiratory pressure (PEEP) in supine position. PET/CT has provided
      valuable insights into the inflammatory response of the lung. Electrical
      impedance tomography has been used to assess lung recruitability and to titrate
      PEEP. Finally, lung ultrasound has proven to be reliable diagnostic tool for
      assessing PEEP-induced recruitment. SUMMARY: Whereas quantitative CT remains the
      gold standard to assess lung morphology, recruitment and hyperinflation of lung
      tissue at different inflation pressures, EIT and LUS have emerged as valuable,
      radiation-free, noninvasive bedside lung imaging tools that should be used
      together with global parameters like lung mechanics and gas exchange to acquire
      additional information on recruitability and ventilation distribution.

PMID- 22395441
TI  - Current world literature.

PMID- 22395444
TI  - Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered
      mitochondria mediated apoptosis in human liver cells (HepG2).
AB  - The wide scale use of Zinc oxide (ZnO) nanoparticles in the world consumer market
      makes human beings more prone to the exposure to ZnO nanoparticles and its
      adverse effects. The liver, which is the primary organ of metabolism, might act
      as a major target organ for ZnO nanoparticles after they gain entry into the body
      through any of the possible routes. Therefore, the aim of the present study was
      to assess the apoptotic and genotoxic potential of ZnO nanoparticles in human
      liver cells (HepG2) and the underlying molecular mechanism of its cellular
      toxicity. The role of dissolution in the toxicity of ZnO nanoparticles was also
      investigated. Our results demonstrate that HepG2 cells exposed to 14-20 MUg/ml
      ZnO nanoparticles for 12 h showed a decrease in cell viability and the mode of
      cell death induced by ZnO nanoparticles was apoptosis. They also induced DNA
      damage which was mediated by oxidative stress as evidenced by an increase in Fpg
      sensitive sites. Reactive oxygen species triggered a decrease in mitochondria
      membrane potential and an increase in the ratio of Bax/Bcl2 leading to
      mitochondria mediated pathway involved in apoptosis. In addition, ZnO
      nanoparticles activated JNK, p38 and induced p53(Ser15) phosphorylation. However,
      apoptosis was found to be independent of JNK and p38 pathways. This study
      investigating the effects of ZnO nanoparticles in human liver cells has provided
      valuable insights into the mechanism of toxicity induced by ZnO nanoparticles.

PMID- 22395445
TI  - Selective cell death of p53-insufficient cancer cells is induced by knockdown of
      the mRNA export molecule GANP.
AB  - Cancer cells often contain p53 abnormalities that impair cell-cycle checkpoint
      progression and cause resistance to various anti-cancer treatments. DNA damage
      occurs at actively transcribed genes during G1-phase in yeast cells that have a
      deficient mRNA export capacity. Here, we show that germinal center-associated
      nuclear protein (GANP), a homologue of yeast Sac3 that is involved in mRNA
      export, is indispensable for ensuring the stability of human genomic DNA and that
      GANP knockdown causes apoptosis and necrosis of p53-insufficient cancer cells.
      Ganp small interfering RNA (siGanp)-induced DNA damage, accompanied by a decrease
      in the number of cells in S-phase, caused late apoptosis and necrosis in p53
      insufficient cancer cells through both caspase-dependent and -independent
      mechanisms. siGanp effectively induced DNA damage leading to cell death in p53
      insufficient cancer cells in vitro and protect the growth of cancer cells
      transplanted into immunocompromized mice, suggesting that siGanp has potential as
      a selective treatment for p53-insufficient cancer cells.

PMID- 22395447
TI  - One pot synthesis of maleimide and hydantoin by Fe(CO)5 catalyzed [2 + 2 + 1] co
      cyclization of acetylene, isocyanate and CO.
AB  - In the presence of a catalytic amount of Fe(CO)(5), terminal acetylenes,
      isocyanates and CO undergo [2 + 2 + 1] cyclization to form substituted maleimides
      and hydantoins; when internal alkynes are used, exclusive maleimide formation is
      observed. While the maleimides can be obtained as the major products, in up to
      90% yield, when the reaction is carried out in CO atmosphere, in absence of CO,
      the hydantoins are formed in up to 87% yield. Formation of maleimides has been
      shown to occur via the formation of a ferrole intermediate, whereas the
      hydantoins are proposed to form through successive insertion of isocyanate into
      the iron-acetylide bond. All compounds were characterized by spectroscopic
      methods and molecular structures of some compounds were established by single
      crystal X-ray diffraction method.

PMID- 22395446
TI  - 3-Nitro-naphthalimide and nitrogen mustard conjugate NNM-25 induces
      hepatocellular carcinoma apoptosis via PARP-1/p53 pathway.
AB  - Hepatocellular carcinoma (HCC) is one of the main causes of death in cancer. Some
      naphthalimide derivatives exert high anti-proliferative effects on HCC. In this
      study, it is confirmed that 3-nitro-naphthalimide and nitrogen mustard conjugate
      (NNM-25), a novel compound conjugated by NNM-25, displayed more potent
      therapeutic action on HCC, both in vivo and in vitro, than amonafide, a
      naphthalimide drug in clinical trials. More importantly, preliminary
      toxicological evaluation also supported that NNM-25 exhibited less systemic
      toxicity than amonafide at the therapeutic dose. The antitumor mechanism of
      conjugates of naphthalimides with nitrogen mustard remains poorly understood up
      to now. Here, we first reported that apoptosis might be the terminal fate of
      cancer cells treated with NNM-25. Inhibition of p53 by siRNA resulted in a
      significant decrease of NNM-25-induced apoptosis, which corroborated that p53
      played a vital role in the cell apoptosis triggered by NNM-25. NNM-25 inhibited
      the PARP-1 activity, AKT phosphorylation, up-regulated the protein expression of
      p53, Bad, and mTOR as well as down-regulating the protein expression of Bcl-2 and
      decreasing mitochondrial membrane potential. It also facilitated cytochrome c
      release from mitochondria to cytoplasm, activated caspase 8, caspase 9, and
      caspase 3 in HepG2 cells in vitro, as also authenticated in H22 tumor-bearing
      mice in vivo. Collectively, the conjugation of naphthalimides with nitrogen
      mustard provides favorable biological activity and thus is a valuable strategy
      for future drug design in HCC therapy.

PMID- 22395448
TI  - Lateral diffusion and exocytosis of membrane proteins in cultured neurons
      assessed using fluorescence recovery and fluorescence-loss photobleaching.
AB  - Membrane proteins such as receptors and ion channels undergo active trafficking
      in neurons, which are highly polarised and morphologically complex. This directed
      trafficking is of fundamental importance to deliver, maintain or remove synaptic
      proteins.    Super-ecliptic pHluorin (SEP) is a pH-sensitive derivative of eGFP
      that has been extensively used for live cell imaging of plasma membrane
      proteins(1-2). At low pH, protonation of SEP decreases photon absorption and
      eliminates fluorescence emission. As most intracellular trafficking events occur
      in compartments with low pH, where SEP fluorescence is eclipsed, the fluorescence
      signal from SEP-tagged proteins is predominantly from the plasma membrane where
      the SEP is exposed to a neutral pH extracellular environment. When illuminated at
      high intensity SEP, like every fluorescent dye, is irreversibly photodamaged
      (photobleached)(3-5). Importantly, because low pH quenches photon absorption,
      only surface expressed SEP can be photobleached whereas intracellular SEP is
      unaffected by the high intensity illumination(6-10).     FRAP (fluorescence
      recovery after photobleaching) of SEP-tagged proteins is a convenient and
      powerful technique for assessing protein dynamics at the plasma membrane. When
      fluorescently tagged proteins are photobleached in a region of interest (ROI) the
      recovery in fluorescence occurs due to the movement of unbleached SEP-tagged
      proteins into the bleached region. This can occur via lateral diffusion and/or
      from exocytosis of non-photobleached receptors supplied either by de novo
      synthesis or recycling (see Fig. 1). The fraction of immobile and mobile protein
      can be determined and the mobility and kinetics of the diffusible fraction can be
      interrogated under basal and stimulated conditions such as agonist application or
      neuronal activation stimuli such as NMDA or KCl application(8,10).     We
      describe photobleaching techniques designed to selectively visualize the recovery
      of fluorescence attributable to exocytosis. Briefly, an ROI is photobleached once
      as with standard FRAP protocols, followed, after a brief recovery, by repetitive
      bleaching of the flanking regions. This 'FRAP-FLIP' protocol, developed in our
      lab, has been used to characterize AMPA receptor trafficking at dendritic
      spines(10), and is applicable to a wide range of trafficking studies to evaluate
      the intracellular trafficking and exocytosis.

PMID- 22395449
TI  - De novo subtype and strain identification of botulinum neurotoxin type B through
      toxin proteomics.
AB  - Botulinum neurotoxins (BoNTs) cause the disease botulism, which can be lethal if
      untreated. There are seven known serotypes of BoNT, A-G, defined by their
      response to antisera. Many serotypes are distinguished into differing subtypes
      based on amino acid sequence, and many subtypes are further differentiated into
      toxin variants. Previous work in our laboratory described the use of a proteomics
      approach to distinguish subtype BoNT/A1 from BoNT/A2 where BoNT identities were
      confirmed after searching data against a database containing protein sequences of
      all known BoNT/A subtypes. We now describe here a similar approach to
      differentiate subtypes BoNT/B1, /B2, /B3, /B4, and /B5. Additionally, to identify
      new subtypes or hitherto unpublished amino acid substitutions, we created an
      amino acid substitution database covering every possible amino acid change. We
      used this database to differentiate multiple toxin variants within subtypes of
      BoNT/B1 and B2. More importantly, with our amino acid substitution database, we
      were able to identify a novel BoNT/B subtype, designated here as BoNT/B7. These
      techniques allow for subtype and strain level identification of both known and
      unknown BoNT/B rapidly with no DNA required.

PMID- 22395450
TI  - Determination of non-steroidal anti-inflammatory drugs and their metabolites in
      milk by liquid chromatography-tandem mass spectrometry.
AB  - Non-steroidal anti-inflammatory drugs are widely used for treatment of animals.
      According to Council Directive 96/23/EC, residues of these drugs must be
      monitored because of the potential risk they pose to the consumers' health. For
      this reason an LC-MS-MS method was developed for detection of wide range of
      NSAIDs, including both "acidic" NSAIDs (carprofen, diclofenac, flunixin,
      meloxicam, phenylbutazone, oxyphenbutazone, tolfenamic acid, mefenamic acid,
      naproxen, ketoprofen, ibuprofen, firocoxib, rofecoxib, and celecoxib) and "basic"
      NSAIDs (four metamizole metabolites). Analytes were extracted from milk samples
      with acetonitrile in the presence of ammonium acetate. One portion of the extract
      was directly analyzed for the presence of metamizole metabolites; a second
      portion was cleaned with an amino cartridge. All NSAIDs were separated on a
      Phenomenex Luna C8(2) column and analyzed by LC-MS-MS in negative (acidic NSAIDs)
      and positive (metamizole metabolites) ion modes. The method was validated in
      accordance with the requirements of Commission Decision 2002/657/EC. Within
      laboratory reproducibility was in the range 7-28%, and accuracy was in the range
      71-116%. The method enabled detection of all the analytes with the expected
      sensitivity, below the recommended concentrations. The method fulfills the
      criteria for confirmatory methods and, because of its efficiency, may also be
      used for screening purposes. The procedure was also successfully verified in the
      proficiency test organized by EU-RL in 2010. As far as the authors are aware,
      this is one of the first methods capable of detecting diclofenac residues below
      the MRL in milk (0.1 MUg kg(-1)). An additional advantage is the possibility of
      simultaneous determination of "acidic" NSAIDs and metamizole metabolites.

PMID- 22395451
TI  - Simultaneous analysis of plasma and CSF by NMR and hierarchical models fusion.
AB  - Because cerebrospinal fluid (CSF) is the biofluid which interacts most closely
      with the central nervous system, it holds promise as a reporter of neurological
      disease, for example multiple sclerosis (MScl). To characterize the metabolomics
      profile of neuroinflammatory aspects of this disease we studied an animal model
      of MScl-experimental autoimmune/allergic encephalomyelitis (EAE). Because CSF
      also exchanges metabolites with blood via the blood-brain barrier, malfunctions
      occurring in the CNS may be reflected in the biochemical composition of blood
      plasma. The combination of blood plasma and CSF provides more complete
      information about the disease. Both biofluids can be studied by use of NMR
      spectroscopy. It is then necessary to perform combined analysis of the two
      different datasets. Mid-level data fusion was therefore applied to blood plasma
      and CSF datasets. First, relevant information was extracted from each biofluid
      dataset by use of linear support vector machine recursive feature elimination.
      The selected variables from each dataset were concatenated for joint analysis by
      partial least squares discriminant analysis (PLS-DA). The combined metabolomics
      information from plasma and CSF enables more efficient and reliable
      discrimination of the onset of EAE. Second, we introduced hierarchical models
      fusion, in which previously developed PLS-DA models are hierarchically combined.
      We show that this approach enables neuroinflamed rats (even on the day of onset)
      to be distinguished from either healthy or peripherally inflamed rats. Moreover,
      progression of EAE can be investigated because the model separates the onset and
      peak of the disease.

PMID- 22395452
TI  - Development and validation of a method for determination of residues of 15
      pyrethroids and two metabolites of dithiocarbamates in foods by ultra-performance
      liquid chromatography-tandem mass spectrometry.
AB  - This paper reports a novel approach for the detection, confirmation, and
      quantification of 15 selected pyrethroid pesticides, including pyrethins, and two
      metabolites of dithiocarbamates in foods by ultra-performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS-MS). The proposed method makes
      use of a modified QuEChERS (quick, easy, cheap, effective, rugged, and safe)
      procedure that combines isolation of the pesticides and sample cleanup in a
      single step. Analysis of pyrethroids and dithiocarbamate metabolites was
      performed by UPLC-MS-MS operated with electrospray and atmospheric pressure
      chemical ionization, respectively. Two specific precursor-product ion transitions
      were acquired per target compound in multiple reaction monitoring (MRM) mode.
      Such acquisition achieved the minimum number of identification points according
      to European Commission (EC) document no. SANCO/10684/2009, thus fulfilling the EC
      point system requirement for identification of contaminants in samples. The
      method was validated with a variety of food samples. Calibration curves were
      linear and covered from 1 to 800 MUg kg(-1) in the sample for all target
      compounds. Average recoveries, measured at mass fractions of 10 and 100 MUg kg(
      1) for pyrethroids and 5 and 50 MUg kg(-1) for dithiocarbamate metabolites, were
      in the range of 70-120% for all target compounds with relative standard
      deviations below 20%. Method limits of quantification (MLOQ) were 10 MUg kg(-1)
      and 5 MUg kg(-1) for pyrethroids and dithiocarbamate metabolites, respectively.
      The method has been successfully applied to the analysis of 600 food samples in
      the course of the first Hong Kong total diet study with pyrethroids and
      metabolites of dithiocarbamates being the pesticides determined.

PMID- 22395453
TI  - Euroanalysis XVI--challenges in modern analytical chemistry.

PMID- 22395454
TI  - The effect of the menopausal transition on body composition and cardiometabolic
      risk factors:  a Montreal-Ottawa New Emerging Team group study.
AB  - OBJECTIVE: Cardiovascular disease is the first cause of mortality in women in
      North America. The risk of cardiovascular disease increases sharply after middle
      age in women, especially after menopause. The aim was to investigate changes in
      body composition and cardiometabolic profile throughout the menopausal
      transition. METHODS: This was a 5-year observational, longitudinal study on the
      menopausal transition. The study included 102 premenopausal women at baseline
      (age, 49.9 +/- 1.9 y; body mass index, 23.3 +/- 2.2 kg/m). Outcome measures
      include menopause status, body composition by dual-energy x-ray absorptiometry
      (total fat mass [FM], trunk FM, and total fat-free mass), waist circumference,
      visceral and abdominal subcutaneous fat, fasting glucose and insulin levels,
      homeostasis model assessment of insulin resistance, plasma lipid levels
      (triglycerides, total cholesterol, and high- and low-density lipoprotein
      cholesterol), and resting blood pressure. RESULTS: Repeated-measure analyses
      revealed significant increases for FM, percentage FM, trunk FM, visceral fat,
      plasma fasting glucose, and high-density lipoprotein cholesterol (0.05 > P <
      0.01) and a significant decrease for plasma glucose levels after follow-up. Those
      who were in perimenopause or postmenopause by year 3 of the study showed a
      significant increase in visceral fat (P < 0.01) compared with baseline. Despite
      some significant changes in the metabolic profile among the menopause statuses,
      the women did not show any cardiometabolic deterioration by the end of the study.
      CONCLUSIONS: Our results suggest that changes in body composition and fat
      distribution can occur in nonobese women as they go through the menopausal
      transition. However, these changes were not accompanied by cardiometabolic
      deteriorations in the present study.

PMID- 22395456
TI  - Microwave-assisted C-3 selective oxidative radical alkylation of flavones.
AB  - Flavones were directly alkylated at the C-3 position in moderate yields using a
      xanthate-based oxidative radical addition procedure. This methodology is a
      suitable synthetic tool for the direct substitution of the vinylic and
      unactivated C-H bond of the C ring of the flavone by an alkyl functionality under
      neutral conditions.

PMID- 22395457
TI  - Reversibly controlled morphology transformation of an amphiphilic DNA-dendron
      hybrid.
AB  - Spherical micelles and nanofibers assembled from an amphiphilic DNA-dendron
      hybrid can be reversibly achieved under optimum assembly conditions. The possible
      morphology transformation mechanism is proposed and further confirmed by X-ray
      diffraction, TEM and DLS experiments.

PMID- 22395455
TI  - Plastid genetic engineering in Solanaceae.
AB  - Plastid genetic engineering has come of age, becoming today an attractive
      alternative approach for the expression of foreign genes, as it offers several
      advantages over nuclear transformants. Significant progress has been made in
      plastid genetic engineering in tobacco and other Solanaceae plants, through the
      use of improved regeneration procedures and transformation vectors with efficient
      promoters and untranslated regions. Many genes encoding for industrially
      important proteins and vaccines, as well as genes conferring important agronomic
      traits, have been stably integrated and expressed in the plastid genome. Despite
      these advances, it remains a challenge to achieve marked levels of plastid
      transgene expression in non-green tissues. In this review, we summarize the basic
      requirements of plastid genetic engineering and discuss the current status,
      limitations, and the potential of plastid transformation for expanding future
      studies relating to Solanaceae plants.

PMID- 22395459
TI  - Non-catalytic functions of DNMT1.
AB  - Mammalian DNA methyltransferase 1 (DNMT1) is essential during early embryo
      development. Consistent with its key role in embryogenesis, depletion of this
      protein in adult somatic cells promotes severe cellular dysfunctions and cell
      death. DNMT1 contains a highly evolutionary conserved C-terminal catalytic DNA
      methyltransferase domain that is thought to be the responsible for the
      maintenance of CpG methylation patterns in the genome. DNMT1 has also a large N
      terminal region with different functional protein-protein and protein-DNA binding
      domains. The multi-domain N-terminal region and the abundant molecular binding
      patterns suggest potential non-catalytic functions for DNMT1. However, this
      hypothesis remains controversial and conflicting results can be found in the
      literature. Here, recent results presenting a functional role for DNMT1
      independent of its catalytic domain are discussed.

PMID- 22395461
TI  - Inhibition of MspI cleavage activity by hydroxymethylation of the CpG site: a
      concern for DNA modification studies using restriction endonucleases.
AB  - In mammalian genomic DNA, cytosine methylation predominantly occurs at CpG
      dinucleotides and provides epigenetic information. In some cells, 5-methyl
      cytosine (5-mC) can be further converted to 5-hydroxymethyl-cytosine (5-hmC) by
      the ten-eleven translocation family of proteins. MspI restriction endonuclease
      has been used to analyze these modified cytosines. However, the kinetic analysis
      in this study revealed that MspI activity is dramatically decreased by
      symmetrical hydroxymethylation of its recognition sequence and partly inhibited
      by hemi-hydroxymethylation, whereas TaqI and HaeIII are relatively resistant to
      hydroxymethylation. Therefore, DNA modification studies that use MspI, for
      example, reduced representation bisulfite shotgun sequencing, quantitative
      analysis of 5-hmC, and cleavage-sensitivity analysis, should be carefully
      interpreted.

PMID- 22395462
TI  - Semi-quantitative immunohistochemical detection of 5-hydroxymethyl-cytosine
      reveals conservation of its tissue distribution between amphibians and mammals.
AB  - 5-Hydroxymethyl-cytosine (5-hmC) is a form of modified cytosine, which has
      recently attracted a considerable attention due to its potential role in
      transcriptional regulation. According to several reports 5-hydroxymethyl-cytosine
      distribution is tissue-specific in mammals. Thus, 5-hmC is enriched in embryonic
      cell populations and in adult neuronal tissue. Here, we describe a novel method
      of semi-quantitative immunohistochemical detection of 5-hmC and utilize it to
      assess the levels of this modification in amphibian tissues. We show that,
      similar to mammalian embryos, 5-hmC is enriched in axolotl tadpoles compared with
      adult tissues. Our data demonstrate that 5-hmC distribution is tissue-specific in
      amphibians, and that strong 5-hmC enrichment in neuronal cells is conserved
      between amphibians and mammals. In addition, we identify 5-hmC-enriched cell
      populations that are distributed in amphibian skin and connective tissue in a
      mosaic manner. Our results illustrate that immunochemistry can be successfully
      used not only for spatial identification of cells enriched with 5-hmC, but also
      for the semi-quantitative assessment of the levels of this epigenetic
      modification in single cells of different tissues.

PMID- 22395460
TI  - Basic concepts of epigenetics: impact of environmental signals on gene
      expression.
AB  - Through epigenetic modifications, specific long-term phenotypic consequences can
      arise from environmental influence on slowly evolving genomic DNA. Heritable
      epigenetic information regulates nucleosomal arrangement around DNA and
      determines patterns of gene silencing or active transcription. One of the
      greatest challenges in the study of epigenetics as it relates to disease is the
      enormous diversity of proteins, histone modifications and DNA methylation
      patterns associated with each unique maladaptive phenotype. This is further
      complicated by a limitless combination of environmental cues that could alter the
      epigenome of specific cell types, tissues, organs and systems. In addition,
      complexities arise from the interpretation of studies describing analogous but
      not identical processes in flies, plants, worms, yeast, ciliated protozoans,
      tumor cells and mammals. This review integrates fundamental basic concepts of
      epigenetics with specific focus on how the epigenetic machinery interacts and
      operates in continuity to silence or activate gene expression. Topics covered
      include the connection between DNA methylation, methyl-CpG-binding proteins,
      transcriptional repression complexes, histone residues, histone modifications
      that mediate gene repression or relaxation, histone core variant stability, H1
      histone linker flexibility, FACT complex, nucleosomal remodeling complexes, HP1
      and nuclear lamins.

PMID- 22395463
TI  - Rapid turnover of DNA methylation in human cells.
AB  - Recent studies demonstrated that cytosine methylation in the genome can be
      reversed without DNA replication by enzymatic mechanisms based on base excision
      repair pathways. Both enzymatic methylation and demethylation mechanisms are
      active in the cell nucleus at the same time. One can hypothesize that the actual
      level of CpG methylation could be the result of a balance between the two
      antagonistic processes with a rapid turnover. In the present study, we used mass
      spectrometry to measure the total methyl-cytosine content of the genome in
      cultured human cells after short incubation with the known methyltransferase
      inhibitor 5-deoxy-azacytidine. A significant decrease of the DNA methylation was
      observed. Indeed, the inhibition of the methylation can only result in a rapid
      reduction of the overall methyl-cytosine level if the process of demethylation is
      simultaneous. These observations suggest that the enzymatic mechanisms
      responsible of the opposing reactions of DNA methylation and demethylation act
      simultaneously and may result in a continuous and rapid turnover of methylated
      cytosines. This conclusion is supported by the observation that 5-deoxy
      azacytidine was incorporated in the genomic DNA of non-dividing cells and could
      be detected as soon as after two hours of incubation, hence providing a
      mechanistic explanation to the inhibition of methyltransferases. The observations
      are compatible with the idea that the enzymatic mechanisms that bring together of
      the opposing reactions of DNA methylation and demethylation act simultaneously
      and may result in a continuous and unsuspected rapid turnover of DNA methylation.
      This conclusion is at odds with the generally accepted view of high stability of
      cytosine methylation where the role of enzymatic demethylation is considered as
      limited to some special situations such as transcription. It places DNA
      methylation in the same category as other epigenetic modifications with covalent
      modifications dynamically added to and removed from the chromatin with high
      turnover rate.

PMID- 22395464
TI  - Mutation of MeCP2 alters transcriptional regulation of select immediate-early
      genes.
AB  - Loss-of-function mutations in the methyl-DNA binding protein MeCP2 are associated
      with neurological dysfunction and impaired neural plasticity. However, the
      transcriptional changes that underlie these deficits remain poorly understood.
      Here, we show that mice bearing a C-terminal truncating mutation in Mecp2 (Mecp2
      ( 308) ) are hypersensitive to the locomotor stimulating effects of cocaine.
      Furthermore, these mice have gene-specific alterations in striatal immediate
      early gene (IEG) induction following cocaine administration. MeCP2 mutant mice
      show normal levels of baseline and cocaine-induced striatal Fos expression
      compared with their wild-type littermates. However, the mutant mice have enhanced
      cocaine-induced transcription of Junb and Arc. At the chromatin level, we find
      increased histone H3 acetylation at gene promoters in the Mecp2 mutant mice
      compared with their wild-type littermates, whereas two sites of repressive
      histone methylation are unchanged. Interestingly, we find that MeCP2 mutant mice
      show increased steady-state association of elongation-competent RNA Polymerase II
      (RNAP II) with the Junb and Arc promoters, whereas levels of RNAP II association
      at the Fos promoter are unchanged. These data reveal a gene-specific effect of
      MeCP2 on the recruitment of RNAP II to gene promoters that may modulate the
      inducibility of IEGs. In addition, our findings raise the possibility that
      aberrant regulation of IEGs including Junb and Arc may contribute to altered
      cocaine-induced neuronal and behavioral plasticity in Mecp2 mutant mice.

PMID- 22395465
TI  - Epigenetic and genetic variation at the IGF2/H19 imprinting control region on
      11p15.5 is associated with cerebellum weight.
AB  - IGF2 is a paternally expressed imprinted gene with an important role in
      development and brain function. Allele-specific expression of IGF2 is regulated
      by DNA methylation at three differentially methylated regions (DMRs) spanning the
      IGF2/H19 domain on human 11p15.5. We have comprehensively assessed DNA
      methylation and genotype across the three DMRs and the H19 promoter using tissue
      from a unique collection of well-characterized and neuropathologically-dissected
      post-mortem human cerebellum samples (n = 106) and frontal cortex samples (n =
      51). We show that DNA methylation, particularly in the vicinity of a key CTCF
      binding site (CTCF3) in the imprinting control region (ICR) upstream of H19, is
      strongly correlated with cerebellum weight. DNA methylation at CTCF3 uniquely
      explains ~25% of the variance in cerebellum weight. In addition, we report that
      genetic variation in this ICR is strongly associated with cerebellum weight in a
      parental-origin specific manner, with maternally-inherited alleles associated
      with a 16% increase in cerebellum weight compared with paternally-inherited
      alleles. Given the link between structural brain abnormalities and
      neuropsychiatric disease, an understanding of the epigenetic and parent-of-origin
      specific genetic factors associated with brain morphology provides important
      clues about the etiology of disorders such as schizophrenia and autism.

PMID- 22395467
TI  - Trophoblast-specific DNA methylation occurs after the segregation of the
      trophectoderm and inner cell mass in the mouse periimplantation embryo.
AB  - The first cell differentiation in the mammalian development separates the
      trophoblast and embryonic cell lineages, resulting in the formation of the
      trophectoderm (TE) and inner cell mass (ICM) in blastocysts. Although a lower
      level of global DNA methylation in the genome of the TE compared with ICM has
      been suggested, the dynamics of the DNA methylation profile during TE/ICM
      differentiation has not been elucidated. To address this issue, first we
      identified tissue-dependent and differentially methylated regions (T-DMRs)
      between trophoblast stem (TS) and embryonic stem (ES) cells. Most of these TS-ES
      T-DMRs were also methylated differentially between trophoblast and embryonic
      tissues of embryonic day (E) 6.5 mouse embryos. Furthermore, we found that the
      human genomic regions homologous to mouse TS-ES T-DMRs were methylated
      differentially between human placental tissues and ES cells. Collectively, we
      defined them as cell-lineage-based T-DMRs between trophoblast and embryonic cell
      lineages (T-E T-DMRs). Then, we examined TE and ICM cells isolated from mouse
      E3.5 blastocysts. Interestingly, all T-DMRs examined, including the Elf5, Pou5f1
      and Nanog loci, were in the nearly unmethylated status in both TE and ICM and
      exhibited no differences. The present results suggest that the establishment of
      DNA methylation profiles specific to each cell lineage follows the first
      morphological specification. Together with previous reports on asymmetry of
      histone modifications between TE and ICM, the results of the current study imply
      that histone modifications function as landmarks for setting up cell-lineage
      specific differential DNA methylation profiles.

PMID- 22395466
TI  - Epigenetic silencing of HNF1A associates with changes in the composition of the
      human plasma N-glycome.
AB  - Protein glycosylation is a ubiquitous modification that affects the structure and
      function of proteins. Our recent genome wide association study identified
      transcription factor HNF1A as an important regulator of plasma protein
      glycosylation. To evaluate the potential impact of epigenetic regulation of HNF1A
      on protein glycosylation we analyzed CpG methylation in 810 individuals. The
      association between methylation of four CpG sites and the composition of plasma
      and IgG glycomes was analyzed. Several statistically significant associations
      were observed between HNF1A methylation and plasma glycans, while there were no
      significant associations with IgG glycans. The most consistent association with
      HNF1A methylation was observed with the increase in the proportion of highly
      branched glycans in the plasma N-glycome. The hypothesis that inactivation of
      HNF1A promotes branching of glycans was supported by the analysis of plasma N
      glycomes in 61 patients with inactivating mutations in HNF1A, where the increase
      in plasma glycan branching was also observed. This study represents the first
      demonstration of epigenetic regulation of plasma glycome composition, suggesting
      a potential mechanism by which epigenetic deregulation of the glycome may
      contribute to disease development.

PMID- 22395468
TI  - Histone deacetylase 3 (HDAC3) participates in the transcriptional repression of
      the p16 (INK4a) gene in mammary gland of the female rat offspring exposed to an
      early-life high-fat diet.
AB  - Maternal exposure to environmental agents throughout pregnancy and lactation may
      affect offspring's mammary gland growth and alter the epigenome. This may
      predispose the offspring's mammary glands to be more susceptible to
      carcinogenesis. The purpose of this study was to examine the effect of a maternal
      high-fat diet on the regulation of p16 (INK4a) gene expression in the mammary
      gland of rat offspring. Timed-pregnant Sprague-Dawley rats were fed one of the
      two diets, a control (C, 16% of fat) or a high fat (HF, 45% of fat) diet,
      throughout gestation and lactation and sacrificed at 12 weeks of age. Compared
      with C, HF offspring showed a decrease of p16 (INK4a) gene expression in the
      mammary gland at both mRNA and protein levels. Chromatin immunoprecipitation
      (ChIP) assay demonstrated that the downregulation of p16 (INK4a) transcription in
      HF offspring was associated with reduced acetylation of histone H4 and increased
      recruitment of histone deacetylase 3 (HDAC3) within the p16 (INK4a) promoter
      region, but was not associated with acetylation of histone H3 or HDAC1.
      Methylated DNA immunoprecipitation (MeDIP) did not detect differences in
      methylation at different regions of the p16 (INK4a) gene between C and HF
      offspring. We conclude that maternal high fat exposure represses p16 (INK4a) gene
      expression in the mammary gland of offspring through changes of histone
      modifications and HDAC3 binding activity within the regulatory regions of the p16
      (INK4a) gene.

PMID- 22395469
TI  - Promoter methylation status of VEGF receptor genes: a possible epigenetic
      biomarker to anticipate the efficacy of intracellular-acting VEGF-targeted drugs
      in cancer cells.
AB  - We evaluated whether the inhibitory effects of vascular endothelial growth factor
      (VEGF)-targeted drugs on the proliferation of cancer cells differed according to
      VEGF receptor (VEGFR) genes, Flt1 and KDR, promoter methylation status. Five
      hyper-VEGFR-methylation and six no-VEGFR-methylation cancer cells were used for
      the present study, together with human umbilical endothelial cells (HUVECs) as a
      control. No-VEGFR-methylation cancer cells showed higher expression of Flt1 and
      KDR than hyper-VEGFR-methylation cancer cells. Hyper-VEGFR-methylation cancer
      cells only showed increased expression and protein levels of Flt1 and KDR after
      treatment with the demethylase 5-aza-2'-deoxycytidine. Two drugs (a VEGF-specific
      antibody, bevacizumab, and a KDR-specific-antibody) targeting extracellular VEGF
      VEGFR signaling and two VEGF-specific-tyrosine kinase inhibitors (PTK/ZK and
      sunitinib) targeting intracellular VEGFR signaling were used in the cell
      proliferation assay. HUVECs showed dose- and time-dependent proliferation
      decrease with all tested drugs over a 72 h incubation period. No- or hyper-VEGFR
      methylation cancer cells showed no significant proliferation differences after
      treatment with VEGF-specific-antibody or VEGFR2-specific-antibody. After PTK/ZK
      or sunitinib treatment, no-VEGFR-methylation cancer cells showed dose- or time
      dependent decreases in proliferation. Hyper-VEGFR-methylation cancer cells also
      showed proliferation inhibition by VEGF-specific-tyrosine kinase inhibitors after
      demethylation of Flt1 and KDR. Proliferation inhibition synergistically increased
      after combination of demethylation with PTK/ZK in hyper-VEGF-methylation cancer
      cells. We observed that intracellular targeting of VEGF-VEGFR signaling could be
      more effective than extracellular targeting of the pathway in the suppression of
      proliferation of some cancer cells. In particular, the efficacy of intracellular
      targeting of VEGF-specific-tyrosine kinase inhibitors might be influenced by the
      epigenetic alteration of VEGFRs.

PMID- 22395470
TI  - Effects of TET2 mutations on DNA methylation in chronic myelomonocytic leukemia.
AB  - TET2 enzymatically converts 5-methyl-cytosine to 5-hydroxymethyl-cytosine,
      possibly leading to loss of DNA methylation. TET2 mutations are common in myeloid
      leukemia and were proposed to contribute to leukemogenesis through DNA
      methylation. To expand on this concept, we studied chronic myelomonocytic
      leukemia (CMML) samples. TET2 missense or nonsense mutations were detected in 53%
      (16/30) of patients. In contrast, only 1/30 patient had a mutation in IDH1 or
      IDH2, and none of them had a mutation in DNMT3A in the sites most frequently
      mutated in leukemia. Using bisulfite pyrosequencing, global methylation measured
      by the LINE-1 assay and DNA methylation levels of 10 promoter CpG islands
      frequently abnormal in myeloid leukemia were not different between TET2 mutants
      and wild-type CMML cases. This was also true for 9 out of 11 gene promoters
      reported by others as differentially methylated by TET2 mutations. We found that
      two non-CpG island promoters, AIM2 and SP140, were hypermethylated in patients
      with mutant TET2. These were the only two gene promoters (out of 14,475 genes)
      previously found to be hypermethylated in TET2 mutant cases. However, total 5
      methyl-cytosine levels in TET2 mutant cases were significantly higher than TET2
      wild-type cases (median = 14.0% and 9.8%, respectively) (p = 0.016). Thus, TET2
      mutations affect global methylation in CMML but most of the changes are likely to
      be outside gene promoters.

PMID- 22395471
TI  - Altered microRNA expression in skeletal muscle results from high-fat diet-induced
      insulin resistance in mice.
AB  - Skeletal muscle insulin resistance induced by a high-fat diet has been implicated
      in the development of type 2 diabetes. However, the precise molecular mechanisms
      involved are only partially understood. Recently, studies have shown that
      microRNAs play an important role in insulin resistance in various tissues. In
      this study, microRNA expression profiles of skeletal muscle of mice fed a high
      fat or normal diet were analyzed using microarrays and the results were confirmed
      by real-time reverse-transcription polymerase chain reaction. Gene Ontology (GO)
      and pathway mapping tools were employed to analyze systemically the biological
      processes and signaling pathways affected by the differential expression of
      microRNAs. In this study, we show that 30 microRNAs are differentially expressed
      between 2 groups of mice. Compared to the mice fed a normal diet, there were 8
      microRNAs up-regulated and 22 microRNAs down-regulated in the high-fat diet-fed
      mice. Furthermore, we confirm that the MAPK signaling pathway highlighted in this
      study is involved in skeletal muscle insulin resistance. These results indicate
      that skeletal muscle insulin resistance induced by a high-fat diet is associated
      with a group of microRNAs. GO and pathway mapping are a valid and effective
      approach for analyzing the function of microRNAs and the results could be a
      guideline for further investigation.

PMID- 22395472
TI  - Five-year results of implants inserted into freeze-dried block allografts.
AB  - PURPOSE: The purpose of this study was to evaluate the outcome after 5 years of
      allografts as bone growth material and success of implants inserted in fresh
      frozen allograft bone. MATERIALS AND METHODS: A total of 20 patients were
      operated and 41 onlay block freeze-dried allografts (calvarial and iliac crest)
      were inserted for bone augmentation. A total of 64 dental implants were performed
      in a two-stage procedure. Four patients had total edentulism and 16 had partial
      edentulism. RESULTS: A total of 41 onlay block allografts were used to augment
      atrophic maxillae and mandibles in 20 patients. In five cases, there were
      horizontal and vertical augmentations. Exposure of bone allograft occurred in
      three cases during the first 6 weeks; all of them located in the posterior area.
      There were no postoperative effects in any of the cases. Fracture was observed in
      one case, the remaining bone was adequate to place the implants. Sixty-two dental
      implants were placed at second stage surgery. There was no loss of implants.
      CONCLUSIONS: The use of fresh-frozen allogenic bone blocks can be considered as
      being reliable for reconstruction of maxillomandibular defects.

PMID- 22395473
TI  - Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian
      families.
AB  - Lynch syndrome (Hereditary nonpolyposis colorectal cancer, HNPCC) is an inherited
      disease with variable phenotype causing the development of colon cancer and other
      malignancies. The basis of the disease is believed to be the mismatch repair gene
      mutations. Genetic screening has been performed among the patients who have
      undergone surgery for colon cancer at the University of Debrecen, Department of
      Surgery. Tumor samples of the screened patients were submitted to
      immunohistochemistry on hMLH1, hMSH2 and hMSH6 genes, microsatellite instability
      testing, followed by sequencing and multiple ligation dependent probe
      amplification. Three families were identified with the missense mutation c.143A>C
      (p.Q48P) of hMLH1 gene. In one of the families a segregation analysis of this
      particular variant was also accomplished. The segregation analysis revealed a
      clear correlation between the tumor cases and the occurrence of this mutation.
      However, none of the analyzed 100 healthy controls demonstrated the same
      aberration. There is only one published evidence in the literature about the
      presence of this rare variant in any population. The Gln to Pro switch in the
      ATPase domain, a conservative region of the hMLH1 gene, creates significant
      changes in the protein structure. These results indicate that this mutation is
      the abnormality responsible for the patients' phenotype and it is feasible that
      this particular aberration occurs more frequently among Hungarian Lynch syndrome
      patients.

PMID- 22395474
TI  - Limited significance of family history for presence of BRCA1 gene mutation in
      Polish breast and ovarian cancer cases.
AB  - It is estimated that about 5-10% of ovarian and 2-5% of all breast cancer
      patients are carriers of a germline BRCA1 or BRCA2 gene mutation. Most families
      with detected BRCA1 or BRCA2 gene mutation are qualified for molecular testing on
      the basis of family history of breast or ovarian cancers. The purpose of our
      study was to establish the frequency of positive family history of cancer in a
      series of Polish consecutive breast and ovarian cancer patients in two groups,
      with and without the BRCA1 gene mutations. We analysed the prevalence of four of
      the most common BRCA1 mutations: 5382insC (c.5266dupC), 300T>G (p.181T>G),
      185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5). The patient group
      consisted of 1,845 consecutive female breast and 363 ovarian cancer cases. 19 out
      of 37 (51%) of BRCA1-positive ovarian cancer patients and 21 out of 55 (39%)
      BRCA1-positive breast cancer had negative family history of breast and/or ovarian
      cancer among first- and second-degree relatives. In ovarian cancer patients,
      negative family history was more frequent in those with 300T>G BRCA1 gene
      mutation than in 5382insC carriers. This finding indicates the necessity of
      searching for 300T>G mutation in families with a single diagnosis of ovarian
      cancer in family. The high frequency of mutations detected in breast cancer
      patients lacking obvious family history shows that breast cancer patients should
      be qualified for genetic testing on the basis of wide clinical and pathological
      criteria.

PMID- 22395475
TI  - Molecular characterization of parathyroid tumors from two patients with
      hereditary colorectal cancer syndromes.
AB  - The tumor suppressor adenomatous polyposis coli (APC) has recently been
      implicated in parathyroid development. We here report clinical, histopathological
      and molecular investigations in parathyroid tumors arising in two patients; one
      familial adenomatous polyposis (FAP) syndrome patient carrying a constitutional
      APC mutation, and one Lynch syndrome patient demonstrating a germline MLH1
      mutation as well as a non-classified, missense alteration of the APC gene. We
      sequenced the entire APC gene in tumor and constitutional DNA from both cases,
      assessed the levels of APC promoter 1A and 1B methylation by bisulfite
      Pyrosequencing analysis and performed immunohistochemistry for APC and
      parafibromin. In addition, copy number analysis regarding the APC gene on
      chromosome 5q21-22 was performed using qRT-PCR. Histopathological workup
      confirmed both tumors as parathyroid adenomas without signs of malignancy or
      atypia. No somatic mutations or copy number changes for the APC gene were
      discovered in the tumors; however, in both cases, the APC promoter 1A was
      hypermethylated while the APC promoter 1B was unmethylated. APC promoter 1B
      specific mRNA and total APC mRNA levels were higher than in normal parathyroid
      samples. Immunohistochemical analyses revealed strong APC protein
      immunoreactivity and positive parafibromin expression in both parathyroid tumors.
      Absence of additional somatic APC mutations and copy number changes in addition
      to the positive APC immunoreactivity obtained suggest that the tumors arose
      without biallelic inactivation of the APC tumor suppressor gene. The finding of
      an unmethylated APC promoter 1B and high APC 1B mRNA levels could explain the
      maintained APC protein expression. Moreover, the findings of positive
      parafibromin and APC immunoreactivity as well as a low MIB-1 proliferation index
      and absence of histopathological features of malignancy/atypical adenoma indicate
      that the parathyroid adenomas arising in these patients did not harbor malignant
      potential.

PMID- 22395476
TI  - The clock gene circuit in Arabidopsis includes a repressilator with additional
      feedback loops.
AB  - Circadian clocks synchronise biological processes with the day/night cycle, using
      molecular mechanisms that include interlocked, transcriptional feedback loops.
      Recent experiments identified the evening complex (EC) as a repressor that can be
      essential for gene expression rhythms in plants. Integrating the EC components in
      this role significantly alters our mechanistic, mathematical model of the clock
      gene circuit. Negative autoregulation of the EC genes constitutes the clock's
      evening loop, replacing the hypothetical component Y. The EC explains our earlier
      conjecture that the morning gene Pseudo-Response Regulator 9 was repressed by an
      evening gene, previously identified with Timing Of CAB Expression1 (TOC1). Our
      computational analysis suggests that TOC1 is a repressor of the morning genes
      Late Elongated Hypocotyl and Circadian Clock Associated1 rather than an activator
      as first conceived. This removes the necessity for the unknown component X (or
      TOC1mod) from previous clock models. As well as matching timeseries and phase
      response data, the model provides a new conceptual framework for the plant clock
      that includes a three-component repressilator circuit in its complex structure.

PMID- 22395477
TI  - Clinical and radiographic evaluation of total hip arthroplasties using porous
      tantalum modular acetabular components: 5-year follow-up of clinical trial.
AB  - OBJECTIVES: Porous tantalum is a biomaterial newly applied for artificial joints.
      We present here 5-years follow-up report of a multicenter clinical trial of total
      hip arthroplasties (THA) with porous tantalum modular acetabular component
      (modular PTC). METHODS: Study participants received 82 hips in 79 cases, with
      61.2 months follow-up on average. Age at operation was 60.9 years. Clinical
      results were evaluated using Merle d'Aubigne Postel score. Presence of implant
      loosening, periacetabular radiolucency, osteolysis, and gap filling were examined
      for radiographic results. RESULTS: Merle d'Aubigne Postel score improved from
      10.0 to 16.4 points. All PTC were radiographically stable, with no evidence of
      progressive radiolucencies. Average polyethylene wear rate was 0.004 mm/year,
      with no periacetabular osteolysis. Fifteen hips (18.3%) showed a gap >1 mm;
      however, all showed bone filling within 12 months. PTC with oversized reaming was
      significantly less likely to have a gap. No implant failure was noted related to
      modularity. Resulting survival rate of modular PTC was 100% at 5 years.
      CONCLUSIONS: Modular PTC showed excellent results at 5-years of follow-up. Some
      hips showed periacetabular gaps, which were filled with bone within 1 year.
      Further follow-up was needed to determine long-term efficacy.

PMID- 22395478
TI  - Leaf-spot disease on European mistletoe (Viscum album) caused by
      Phaeobotryosphaeria visci: a potential candidate for biological control.
AB  - Viscum album (European mistletoe), a perennial, evergreen, hemiparasitic shrub,
      infects a wide range of woody species. It adversely affects the height and
      diameter of growth and it is associated with increased mortality of its hosts.
      There is no effective control methods against it. We have found a specific
      hyperparasitic fungus, which can completely destroy European mistletoe by
      infecting its branches, leaves and berries. Both morphological and molecular
      identification, based on ribosomal internal transcribed spacer sequences (rDNA
      ITS), established its identity as Phaeobotryosphaeria visci. Our analysis also
      revealed unexpected ITS variability, as compared to the previous studies, that
      needs to be considered in identifying of this pathogen. Because of its efficient
      pathogenicity this fungus might be a good candidate for biological control of
      mistletoe.

PMID- 22395479
TI  - Enhancement of biodesulfurization by Pseudomonas delafieldii in a ceramic
      microsparging aeration system.
AB  - A 700 ml membrane-aerated, stirred glass reactor equipped with four vertical
      baffles was constructed. Biodesulfurization of model oil (n-dodecane containing
      dibenzothiophene-DBT) and hydrodesulfurized diesel was carried out using
      Pseudomonas delafieldii strain R-8. Microbubble aeration gave an activity of 1.3
      mg DBT removed g(-1) h(-1) and 277 MUg sulfur g(-1) h(-1) for model oil and
      hydrodesulfurized diesel, respectively. These values were 1.9- and 1.6-times
      higher than using a traditional bubble aeration process. This is a promising
      method for the biodesulfurization of petroleum feedstocks.

PMID- 22395480
TI  - Short-term effects of INGAP and Reg family peptides on the appearance of small
      beta-cells clusters in non-diabetic mice.
AB  - The Reg3 peptides INGAP-PP and human Reg3alpha/beta (HIP) have been hypothesized
      to stimulate beta-cell neogenesis in the pancreas. Administration of INGAP-PP has
      been shown to cause an increase in beta-cell mass in multiple animal models,
      reverse streptozotocin (STZ) induced diabetes in mice and reduces HbA1c levels in
      type 2 diabetic humans. In this study, we have examined the ability of the INGAP
      PP and HIP peptides to induce beta-cell formation in vivo in normal mice through
      short-term administration of the peptides. We assessed the peptides ability to
      induce an increase in extra-islet insulin-positive cell clusters by looking at
      beta-cell number by point counting morphometry on pancreata that had been
      randomized using the smooth fractionator principle in non-diabetic NMRI mice
      after short-term injections of the peptides (5 d). Five day continuous BrdU
      labeling was used to determine if the new beta-cells were derived from
      replicating beta-cells. Real time quantitative RT-PCR and immuno-histochemistry
      was used to analyze changes in pancreatic transcription factor expression. A 1.5-
      to 2-fold increase in the volume of small extra-islet insulin-positive clusters
      post 5 d treatment with INGAP-PP and HIP as compared with mice treated with a non
      peptide control or scrambled peptide (p<0.05) (n = 7) was found. Five day
      continuous BrdU infusion during the 5 d period showed little or no incorporation
      in islets or small insulin clusters. Five days of treatment with INGAP-PP or HIP,
      showed a tendency toward increased levels of pancreatic progenitor markers such
      as Ngn3, Nkx6.1, Sox9 and Ins. These are the first studies to compare and
      indicate that the human Reg3 alpha/beta (HIP) peptide has similar bioactivity in
      vivo as INGAP by causing formation of small beta-cell clusters in extra-islet
      pancreatic tissue after only 5 d of treatment. Upregulation of pancreatic
      transcription factors may be part of the mechanism of action. 

PMID- 22395481
TI  - Factors associated with non-orthotopic urinary diversion after radical
      cystectomy.
AB  - INTRODUCTION: Preoperative factors favoring the performance of non-orthotopic
      bladder substitution (OBS) after radical cystectomy for muscle-invasive bladder
      cancer were identified. PATIENTS AND METHODS: We retrospectively reviewed the
      medical records of 730 patients who underwent radical cystectomy for urothelial
      carcinoma of the bladder. After excluding 75 patients who were unable to undergo
      OBS due to the tumor location or elevated serum creatinine level, we assessed the
      preoperative factors in the remaining 655 patients. Multivariate logistic
      regression analysis was performed to identify the independent preoperative
      predictors of type of urinary diversion. RESULTS: Of the 655 patients, 171
      (26.1%) underwent non-OBS. Patients who underwent non-OBS were more likely to be
      older and females, to have a lower educational status, non-organ confined
      disease, more comorbid medical conditions, more impaired performance status,
      lower body mass index, anemia, azotemia, and hypoalbuminemia, and to be treated
      by less-experienced surgeons (P < 0.05 each). After adjusting for provider-based
      factors, multivariate analysis showed that factors independently associated with
      non-OBS included advanced age (odds ratio [OR] 4.10, P < 0.001), female gender
      (OR 2.08, P = 0.027), ECOG performance status (>= 1 vs 0, OR 5.20, P < 0.001),
      low educational status (OR 1.59, P = 0.042), clinically node-positive disease (OR
      2.36, P = 0.003), anemia (OR 1.67, P = 0.041), azotemia (OR 3.97, P < 0.001), and
      hypoalbuminemia (OR 1.84, P = 0.046). CONCLUSION: Several patient-based as well
      as provider-based factors were associated with the type of urinary diversion
      after radical cystectomy. Advanced age, female gender, low performance status,
      low education level, clinically node-positive disease, anemia, hypoalbuminemia,
      and azotemia were associated with non-OBS, as surgery was performed by relatively
      inexperienced surgeons.

PMID- 22395482
TI  - Etiological factors in primary hepatic B-cell lymphoma.
AB  - Sixty-four cases of malignant lymphoma involving the liver were examined. Of
      these, 20 cases were histologically confirmed to be primary hepatic B-cell
      lymphoma. Twelve of these 20 cases were diffuse large B-cell lymphoma (DLBCL) and
      eight cases were mucosa-associated lymphoid tissue (MALT) lymphoma. Of the 12
      cases of DLBCL, six were immunohistologically positive for CD10 and/or Bcl6
      (indicating a germinal center phenotype), six were positive for Bcl2, and five
      were positive for CD25. Eight of the 12 DLBCL cases (66.7%) and two of the eight
      MALT lymphoma cases (25%) had serum anti-hepatitis C virus (HCV) antibodies and
      HCV RNA. The incidence of HCV infection was significantly higher in the hepatic
      DLBCL cases than in systemic intravascular large B-cell cases with liver
      involvement (one of 11 cases, 9.1%) and T/NK-cell lymphoma cases (one of 19
      cases, 5.3%) (p < 0.01 for both). Two hepatic DLBCL cases (16.7%) had rheumatoid
      arthritis treated with methotrexate, and four MALT lymphoma cases (50%) had
      Sjogren's syndrome, primary biliary cirrhosis, or autoimmune hepatitis; one case
      in each of these two groups was complicated by chronic HCV-seropositive
      hepatitis. Although primary hepatic lymphoma is rare, persistent inflammatory
      processes associated with HCV infection or autoimmune disease may play
      independent roles in the lymphomagenesis of hepatic B cells.

PMID- 22395484
TI  - Urinary bladder chondroma.

PMID- 22395483
TI  - Deregulation of a distinct set of microRNAs is associated with transformation of
      gastritis into MALT lymphoma.
AB  - The mechanisms underlying the transformation from chronic Helicobacter pylori
      gastritis to gastric extranodal marginal zone lymphoma (MALT lymphoma) are poorly
      understood. This study aims to identify microRNAs that might be involved in the
      process of neoplastic transformation. We generated microRNA signatures by RT-PCR
      in 68 gastric biopsy samples representing normal mucosa, gastritis, suspicious
      lymphoid infiltrates, and overt MALT lymphoma according to Wotherspoon criteria.
      Analyses revealed a total of 41 microRNAs that were significantly upregulated (n
      = 33) or downregulated (n = 8) in succession from normal mucosa to gastritis and
      to MALT lymphoma. While some of these merely reflect the presence of lymphocytes
      (e.g. miR-566 and miR-212) or H. pylori infection (e.g. miR-155 and let7f), a
      distinct set of five microRNAs (miR-150, miR-550, miR-124a, miR-518b and miR-539)
      was shown to be differentially expressed in gastritis as opposed to MALT
      lymphoma. This differential expression might therefore indicate a central role of
      these microRNAs in the process of malignant transformation.

PMID- 22395485
TI  - TONNEAU2/FASS regulates the geometry of microtubule nucleation and cortical array
      organization in interphase Arabidopsis cells.
AB  - Organization of microtubules into ordered arrays involves spatial and temporal
      regulation of microtubule nucleation. Here, we show that acentrosomal microtubule
      nucleation in plant cells involves a previously unknown regulatory step that
      determines the geometry of microtubule nucleation. Dynamic imaging of interphase
      cortical microtubules revealed that the ratio of branching to in-bundle
      microtubule nucleation on cortical microtubules is regulated by the Arabidopsis
      thaliana B'' subunit of protein phosphatase 2A, which is encoded by the
      TONNEAU2/FASS (TON2) gene. The probability of nucleation from gamma-tubulin
      complexes localized at the cell cortex was not affected by a loss of TON2
      function, suggesting a specific role of TON2 in regulating the nucleation
      geometry. Both loss of TON2 function and ectopic targeting of TON2 to the plasma
      membrane resulted in defects in cell shape, suggesting the importance of TON2
      mediated regulation of the microtubule cytoskeleton in cell morphogenesis. Loss
      of TON2 function also resulted in an inability for cortical arrays to reorient in
      response to light stimulus, suggesting an essential role for TON2 and microtubule
      branching nucleation in reorganization of microtubule arrays. Our data establish
      TON2 as a regulator of interphase microtubule nucleation and provide experimental
      evidence for a novel regulatory step in the process of microtubule-dependent
      nucleation.

PMID- 22395487
TI  - Influence of mineralization and microporosity on tissue elasticity: experimental
      and numerical investigation on mineralized turkey leg tendons.
AB  - A combined experimental and numerical study correlating indentation stiffness
      with mineralization and microporosity was performed on mineralized turkey leg
      tendon. Two distinct tissue morphologies were distinguished by quantitative
      backscattered electron imaging and called "circumferential" and "interstitial"
      zones. These two zones showed different tissue organization, microporosity, and
      mineralization. Stiffness, measured by microindentation, was also different in
      the two zones. The mean field method of modeling of mineralized collagen fibers
      was employed to explain the differences.

PMID- 22395486
TI  - Pulsing of membrane potential in individual mitochondria: a stress-induced
      mechanism to regulate respiratory bioenergetics in Arabidopsis.
AB  - Mitochondrial ATP synthesis is driven by a membrane potential across the inner
      mitochondrial membrane; this potential is generated by the proton-pumping
      electron transport chain. A balance between proton pumping and dissipation of the
      proton gradient by ATP-synthase is critical to avoid formation of excessive
      reactive oxygen species due to overreduction of the electron transport chain.
      Here, we report a mechanism that regulates bioenergetic balance in individual
      mitochondria: a transient partial depolarization of the inner membrane. Single
      mitochondria in living Arabidopsis thaliana root cells undergo sporadic rapid
      cycles of partial dissipation and restoration of membrane potential, as observed
      by real-time monitoring of the fluorescence of the lipophilic cationic dye
      tetramethyl rhodamine methyl ester. Pulsing is induced in tissues challenged by
      high temperature, H(2)O(2), or cadmium. Pulses were coincident with a pronounced
      transient alkalinization of the matrix and are therefore not caused by uncoupling
      protein or by the opening of a nonspecific channel, which would lead to matrix
      acidification. Instead, a pulse is the result of Ca(2+) influx, which was
      observed coincident with pulsing; moreover, inhibitors of calcium transport
      reduced pulsing. We propose a role for pulsing as a transient uncoupling
      mechanism to counteract mitochondrial dysfunction and reactive oxygen species
      production.

PMID- 22395489
TI  - Current world literature.

PMID- 22395492
TI  - Regioselective solvent-dependent benzannulation of conjugated enynes.
AB  - The transformation of enynes under cobalt-catalysis leads to symmetrical
      benzannulation products in dichloromethane. In tetrahydrofuran the cobalt
      catalysed reactions afforded the unprecedented unsymmetrical benzannulation
      products in moderate to good yields and good regioselectivities. In addition,
      cyclotrimerisation of the alkyne subunit can be realised when electron-deficient
      enynes are applied in the cobalt-catalysed transformations to generate 1,2,4
      trivinylbenzene derivatives using tetrahydrofuran as solvent.

PMID- 22395493
TI  - Vascular calcifications in chronic kidney disease--clinical management.
AB  - Chronic kidney disease (CKD) patients could present various types of
      calcifications causing different pathological conditions that would contribute to
      the renal disease progression and high risk of mortality. Extra-skeletal
      calcifications represent a common consequence of mineral bone disorders in CKD
      patients. Vascular calcifications represent a complex systemic manifestation
      caused by phospho-calcium homeostasis disorders, by imbalance among promoters and
      inhibitors of calcification and the presence of various arterial diseases and
      other risk factors. Consequently, vascular calcification can be considered an
      active pathological process that resembles osteogenesis. Therefore, before
      starting a suitable therapy for the prevention or delay of vascular
      calcifications, our recommendations are: to perform lateral abdominal radiography
      or CT-based techniques in CKD stages 3-5 patients for an early vascular
      calcification detection, to assess thoroughly patients presenting
      hyperphosphatemia, hyperparathyroidism, vitamin D deficiency and to understand
      clearly the pathophysiology of arterial calcification and calciphylaxis.

PMID- 22395494
TI  - Cannibalism in a benign soft tissue tumor (giant-cell tumor of the tendon sheath,
      localized type): a study of 66 cases.
AB  - Cellular cannibalism refers to a phenomenon where a living cell is phagocytosed
      into a tumoral cell, where it eventually dies. With the exception of cells in
      suspension, cellular cannibalism has only been observed with malignant tumors.
      The finding of occasional images of cannibalism in our daily biopsies of giant
      cell tumors of the tendon sheath led us to examine this phenomenon further in a
      retrospective study of 66 cases from our archives. In each case, four
      morphological features were evaluated: evidence of giant cells, cannibalism,
      xanthomatous cells, and hemosiderin deposits. Five cases were randomly selected
      for further immunohistochemical study with the following antibodies: CD68,
      vimentin, leukocytary common antigen (LCA), Bcl-2 oncoprotein, p53, caspase-3,
      and Bax. Patients included 35 (53.03%) females and 31 (46.97%) males. Mean age
      was 50.73 years (range from 14 to 75 years). Giant cells were found in all cases
      but one (98.48%). Cannibalism was found in 56 cases (84.34%) and this phenomenon
      was graded as 1 in 35 cases, 2 in 13 cases, and 3 in six cases. The internalized
      cells frequently appeared apoptotic. Immunohistochemical analysis revealed that
      the internalized cells as well as the cannibal cells expressed CD68.

PMID- 22395495
TI  - Nanostructural features of diabetic podocytopathy.
AB  - The earliest glomerular lesion during the diabetic nephropathy is considered by
      many authors to be the so-called podocytopathy. Microalbuminuria is an early
      clinical marker of diabetic nephropathy that results from damages of the
      glomerular filtration barrier at the level of the highly differentiated
      podocytes. Thus, the diabetic podocytopathy includes cellular hypertrophy, foot
      process effacement, detachment from glomerular basement membrane (GBM), and
      apoptosis. The present paper is reviewing all these features and some additional
      ultrastructural transformations concerning the podocytes involved in the diabetic
      kidney disease.

PMID- 22395496
TI  - Carotid intima-media thickness and plaque as surrogate biomarkers of
      atherosclerosis among consecutive women with systemic lupus erythematosus.
AB  - BACKGROUND: In recent years, there has been a growing interest in understanding
      the pathogenic pathways of premature accelerated atherosclerosis (AS) in systemic
      lupus erythematosus (SLE). However, the role of both traditional and non
      traditional, SLE-specific risk factors is still under debate. AIM: To assess
      surrogate biomarkers of subclinical AS in SLE and to evaluate potential relations
      with cardiovascular risk factors. PATIENTS AND METHODS: Prospective observational
      study on 35 consecutive SLE women (ACR 1987 diagnostic criteria) evaluated
      according to a standard protocol including traditional cardiovascular risk
      factors (hypertension, obesity, diabetes mellitus, cigarette smoking, abnormal
      lipid metabolism), SLE-specific risk factors (renal disease, SLE activity and
      duration, corticosteroid therapy) and surrogate biomarkers of subclinical AS
      (carotid intima-media thickness, plaque) (B-mode color Doppler ultrasound, 7-10
      MHz probe). Data were analyzed in SPSS 16 software, p<0.05. RESULTS: Significant
      differences (p<0.05) among subgroups (with and without plaque, thickened and
      normal intima) have been registered; moreover, statistical significant
      correlations between cIMT and age (r=0.476), age at onset (r=0.451), VLDL
      (r=0.382), hsCRP (r=0.436), Framingham score (r=0.421) have been reported. In
      addition, significant association between homocysteine and SLE-duration
      (r=0.460), SLEDAI (r=0.466), SLICC/ACR (r=0.846) has been demonstrated, while
      hsCRP was associated with ESR (r=0.472), C3 (r=0.396), SLEDAI (r=0.569) and age
      (r=-0.681). Several predictors for increased cIMT have also been identified
      (ANOVA): hsCRP (p=0.016), VLDL (p=0.037), Framingham (p=0.012). CONCLUSIONS: Our
      data advocate for increased cardiovascular burden in SLE and support the value of
      cIMT and carotid plaque as surrogate AS biomarkers in women with SLE.

PMID- 22395497
TI  - Skeletal and dentoalveolar changes in the maxillary bone morphology using two-arm
      maxillary expander.
AB  - OBJECTIVE: The purpose of this study was to evaluate the dental and skeletal
      changes in the maxillary bone morphology, produced by two-arm rapid palatal
      expansion appliances. PATIENTS AND METHODS: The study included 22 girls with an
      average age of 11.9 years treated with RPE appliances at the Department of
      Pedodontics and Orthodontics, Faculty of Dentistry, Timisoara, Romania. We
      evaluated the changes on study casts, using an optical 3D scanner--Activity 101
      (SmartOptics) and also on radiographs. The level of statistical significance was
      set by comparing the changes between pre and post treatment values. We also used
      the Pearson's correlation coefficient (r) to measure the strength of the
      association between the recorded measurements. The correlations were significant
      at p<0.05. RESULTS: Significant changes were found in intermolar width change,
      interpremolar width change, molar tipping and alveolar tipping. Less significant
      changes were found in molar rotation and palatal depth change. After rapid
      maxillary expansion, five of the 21 correlations were found to be statistically
      significant. Positive medium correlations were found between intermolar width
      change and alveolar tipping and between interpremolar width change and alveolar
      tipping. A negative medium correlation was found between palatal depth change and
      alveolar tipping. Weak, but statistically significant correlations were found
      between intermolar width change and interpremolar width change and between
      intermolar width change and palatal depth change. No statistically significant
      correlation was found between the other variables. CONCLUSIONS: This type of
      maxillary expander is capable of expanding the maxillary dentition and alveolar
      process, opening the midpalatal suture and changing the maxillary bone
      morphology. The most remarkable changes occurred in the transverse plane. Future
      research is required to evaluate a larger group of patients.

PMID- 22395498
TI  - Nestin and caveolin-1 in the diagnosis of GISTs.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal
      neoplasias of the gastrointestinal tract, typically expressing c-kit (CD117) and
      CD34. Recently, it was reported that nestin and caveolin-1 are also expressed in
      some human sarcomas, GISTs included. We performed a retrospective study on
      formalin fixed, paraffin embedded samples from 81 cases of confirmed GISTs,
      aiming to characterize their immunohistochemical profile, including nestin and
      caveolin-1 expressions. Tissue samples were evaluated immunohistochemically for
      CD117, CD34, nestin and caveolin-1. The patients (M:F 36:45), aged 46 to 84
      years, had spindle cell type GISTs in 56.7% of cases, epithelioid in 30.8% and
      mixed pattern in 12.3%. Immunohistochemically, CD117 was positive in 88.9% of
      GISTs, CD34 in 85.1%, nestin in 77.7% and caveolin-1 in 71.6% of the tumors. Of
      nine c-kit negative GISTs, 66.7% expressed nestin, the same as caveolin-1 and
      44.5% expressed both nestin and caveolin-1. Statistical analysis using Kendall's
      and Spearman's tests revealed significant correlations between nestin and
      caveolin-1 expressions (p=0.024). Our results suggest that nestin and caveolin-1
      could be considered sensitive markers in GISTs, together with CD117 and CD34, for
      diagnostic purposes. Their significant expression in CD117 negative GISTs could
      represent an immunohistochemical alternative in establishing the diagnosis of
      these tumors.

PMID- 22395499
TI  - Validation of PCR-RFLP techniques for the evaluation of codon 72 of p53 and
      CYP1A1 gene's polymorphisms in relation with ovarian cancer in a Romanian
      population.
AB  - Epidemiological studies suggest that the onset and progression of ovarian cancer
      are associated with the presence of estrogens. CYP1A1 gene has two polymorphisms,
      which may affect the estrogens' metabolites and contribute to increased
      susceptibility to neoplastic transformation of ovarian cells. P53 is a tumor
      suppressor gene, which acts to preserve stability of human genome. Codon 72
      polymorphism of p53 gene was correlated with susceptibility for ovarian cancer.
      The aim of our study was to validate the use of PCR-RFLP techniques for the
      evaluation of p53 codon 72 and CYP1A1 gene polymorphisms in relation with ovarian
      cancer in a Romanian population and to evaluate gene-environment interaction in
      this context. The case-control study included 42 subjects. The assessment of risk
      and protective factors was performed using a questionnaire. Polymorphisms of
      CYP1A1 and p53 genes were assessed using the validated PCR-RFLP techniques. The
      statistical analysis was performed using Epi Info 3.5.1 software. Frequency of
      Arg/Arg genotype of p53 gene was higher among cases (43%) compared with controls
      (33.3%), but the difference was not statistically significant (p=0.75). The
      presence of Ile/Val polymorphism of CYP1A1 gene was identified in 9.5% of the
      cases and the MspI polymorphism of CYP1A1 gene was not identified in our
      subjects. Validation of techniques consisted in the optimization of RFLP methods
      for p53 and CYP1A1 genes polymorphism analyzing that allowed highlighting the
      existence of codon 72 polymorphism of p53 gene and Ile/Val polymorphism of CYP1A1
      gene in the population from this region.

PMID- 22395500
TI  - Inflammatory reaction in chronic periodontopathies in patients with diabetes
      mellitus. Histological and immunohistochemical study.
AB  - Chronic periodontopathies and diabetes mellitus are two clinical entities, which
      reciprocally condition one another. The periodontal disease is considered a major
      complication, which induces an unfavorable evolution of diabetes mellitus.
      Diabetes mellitus is an endocrine disease which favors the occurrence of
      periodontopathy through gum's microvascular disorders, the selection and
      development of an aggressive bacterial plaque and through an exaggerate
      inflammatory response to the microflora within the oral cavity. Both diabetes
      mellitus and periodontal disease have an increasing incidence in the whole world.
      Development of periodontopathy is related to the aggression of bacterial flora in
      dental plaque, flora that is influenced on its turn by the evolution of diabetes
      mellitus. In our study, we have evaluated the inflammatory reaction in
      periodontium in patients with slowly and progressive periodontitis in patients
      with diabetes mellitus who had diabetes longer than five years. It has been found
      that all patients presented a chronic inflammatory infiltrate, abundant, with
      round mononuclear cells of lymphocyte, plasma cells and macrophage type, with non
      homogenous arrangement, more intensely where the covering epithelium presented
      erosions or necrotic areas. Out of the immunity system cells, the most numerous
      where of T-lymphocytes type.

PMID- 22395501
TI  - Immunohistochemical expression of anti-CD68 antibody in atherosclerotic plaque.
AB  - Inflammation of the vascular wall is an essential event in the development of
      atherosclerosis, the main leukocytes of the inflammatory infiltrate being the
      monocyte/macrophages. These cells are very heterogeneous and rapidly change their
      function in response to signals received from the local environment. PURPOSE: The
      aim of this research was to study the immunohistochemical expression of the anti
      CD68 antibody at the level of the atherosclerotic plaque. MATERIALS AND METHODS:
      We used tissue samples obtained by endarterectomies in patients with symptomatic
      atherosclerotic lesions. Inflammatory reaction was highlighted in the arterial
      wall by immunohistochemistry using an anti-CD68 monoclonal antibody that marks
      normal or pathological monocytes/macrophages. RESULTS AND DISCUSSION: The types
      of analyzed atherosclerotic lesions showed a positive reaction with the anti-CD68
      antibody, varying in distribution and intensity in the vascular intima. The CD68
      was positive in macrophages depending on the extent of the inflammatory reaction.
      CONCLUSIONS: The presence of many macrophages in the atherosclerotic plaques
      indicates a chronic inflammatory reaction, accompanied by fibroblast
      proliferation and connective tissue changes that influence the stability of the
      plaques.

PMID- 22395502
TI  - Microvascular density in non-Hodgkin B-cell lymphomas measured using digital
      morphometry.
AB  - INTRODUCTION: The growth of solid tumors requires the development of
      microvessels, therefore tumor expansion depends on angiogenesis. Microvessels
      provide nutrients and oxygen and remove catabolytic substances, while endothelial
      cells produce growth factors for tumor cells in a paracrine fashion. The
      microvascular component of a tumor also plays a role in the metastatic capacity
      of the tumor, enabling the tumor cells to spread to distant locations by
      providing a large endothelial surface. AIM: The purpose of this study was to
      review the literature about angiogenesis regarding malignant lymphomas and to
      perform basic measurements by means of digital morphometric methods in large B
      cell lymphomas and follicular lymphomas. MATERIALS AND METHODS: After thorough
      analyzing currently available assessment methods, we performed angiogenesis
      assessment on 19 randomly selected cases, from paraffin-embedded specimens using
      digital morphometry. We used immunohistochemistry and the CD34 antigen to mark
      microvessels. We measured average vascular diameter and a previously successfully
      applied digital morphometric method to quantify the extent of endothelial area.
      RESULTS: According to literature data, our knowledge and understanding of
      angiogenesis grew rapidly from early studies such as Folkman's classic paper.
      Many studies showed that angiogenesis plays a key role in the biology of tumors
      and therefore the study of angiogenesis might open new therapeutic possibilities.
      There have been many studies of angiogenesis in malignant lymphomas, however not
      as many articles as in other tumor types. Our morphometric studies showed there
      are statistically significant differences between diffuse large cell lymphoma
      (DLBCL) and follicular lymphoma (FL) regarding average vascular diameter and that
      high grade lymphomas tend to have a greater CD34+ endothelial area.

PMID- 22395503
TI  - IL-17 patterns in synovium, serum and synovial fluid from treatment-naive, early
      rheumatoid arthritis patients.
AB  - BACKGROUND: There are actually becoming controversial data regarding the profiles
      of interleukin-17 (IL-17) in different pathogenical stages of rheumatoid
      arthritis (RA). OBJECTIVES: To assessing the IL-17 patterns in synovium, serum
      and synovial fluid from treatment-naive early RA patients and to identifying
      potential correlations with disease activity markers and with synovial
      histopathological profile. MATERIALS AND METHODS: Serum samples from 30 treatment
      naive early RA patients were evaluated for C-reactive protein (CRP), erythrocytes
      sedimentation rate (ESR), rheumatoid factor (RF), anti-cyclic citrullinated
      peptide antibodies (anti-CCP). IL-17A levels were also assessed in serum and
      synovial fluid (SF). Disease activity score (DAS28) calculation was done for all
      patients. Control serum and SF samples were obtained from 29 patients with
      osteoarthritis (OA); control synovium specimens were obtained from eight patients
      with OA and during surgery for knee tear ligaments. Histopathological (Hp) score,
      immunohistochemical reactivity for IL-17 were also assessed in synovium of early
      RA patients and controls. Dependencies between serum and synovial profile of IL
      17A and the other parameters were statistically tested. RESULTS: In early RA
      patients, strong correlations of serum and SF IL-17A levels were found with ESR,
      CRP, RF, anti-CCP, Hp score and IL-17 synovial immunoreactivity; a good
      correlation was noted with DAS28 score. Also, strong correlation was noted
      between serum and SF IL-17A levels. CONCLUSIONS: In early stages of untreated RA,
      simultaneous IL-17 assessment of serum, SF and synovium might be valuable in
      defining activity and predictive patterns, given that synovium is highly
      suggestive for an disease aggressivity and might express specific therapeutically
      targets.

PMID- 22395504
TI  - Operational scores in the diagnosis of chronic hepatitis. A semi-quantitative
      assessment.
AB  - Starting from the quantification of the specific lesions for chronic hepatitis B
      and C, our study focused on (i) the correspondence between the necroinflammatory
      activity and the fibrosis stage ascertained through the Ishak scoring system,
      (ii) the classification overlaps and differences of Ishak vs. METAVIR score. The
      study group consisted of 202 cases with chronic hepatitis B and 751 cases with
      chronic hepatitis C, diagnosed based on liver biopsies. The fragments of hepatic
      tissue were routinely processed and stained with Hematoxylin-Eosin, trichrome
      Szekely, Gordon-Sweet silver impregnation, and Periodic Acid-Schiff. A
      semiquantitative evaluation was performed using the Ishak (for hepatitis B and C)
      and the METAVIR (for hepatitis C) scoring systems. Our results revealed that the
      comparison between hepatitis B and C, based on the necroinflammatory activity and
      fibrosis, is able to offer through the numeric values of the Ishak scoring system
      accurate proofs, which support the aggressivity of hepatitis C, because it
      develops fibrosis more quickly, even on the background of mild necroinflammatory
      activity. Also, our data showed that the necroinflammatory activity and the
      fibrosis are not processes which progress in a consistent pattern. The
      application of the METAVIR scoring system for the cases with chronic hepatitis C
      confirmed that there is not a direct correlation between necroinflammation and
      fibrosis. The Ishak scoring system provides through the wide range of numeric
      values attributed for the evaluation of necroinflammatory activity and fibrosis
      far more precise criteria for the appraisal of the degree of damage to the
      hepatic parenchyma at the time of the diagnosis. Supplementary, the METAVIR
      scoring system allows for the hepatitis C an assessment of the entire histologic
      activity, including the interface hepatitis and the associated lobular necrosis
      components. The scoring systems have unavoidably strengths and weaknesses, but
      the choice of a specific one must reflect the consensus between the pathologists
      and the clinicians, relying on their experience.

PMID- 22395505
TI  - P53, p16 and Ki67 immunoexpression in oral squamous carcinomas.
AB  - In this study, we have analyzed clinically, histopathologically and
      immunohistochemically a total of 34 cases of oral squamous carcinoma in 11 of the
      cases being identified adjacent epithelial dysplastic lesions. Carcinomas were
      diagnosed in patients aged 40-60 years, males, with chronic exposure to tobacco
      and/or alcohol, being located especially on the lips. Well-differentiated
      carcinomas have been predominant (52.9%) in stage I/II tumoral (88.3%).
      Immunoexpression analysis of p53, p16 and Ki67 did not reveal statistically
      significant differences between the expression of markers and clinical or
      histopathological parameters, except Ki67 whose increased expression was
      associated to the decrease of the degree of tumoral differentiation and with high
      degree dysplasia. The positivity index and the intensity of reaction were
      increased at the level of dysplasic epithelium for p16 and at the level of
      tumoral invasion front for the p53 and Ki67. The study highlights the value of
      the immunostain for p16 in identifying dysplasic lesions and predictive
      importance of p53 and Ki67 markers in identifying the aggressive forms of oral
      carcinomas.

PMID- 22395506
TI  - Surgical management of the esogastric junction adenocarcinoma according to its
      histological types.
AB  - Most adenocarcinomas of the esophagus occur in the area of the cardia and
      originate in islands of gastrointestinal mucosa, less often in the submucosal
      glands, and are usually histologically similar to gastric adenocarcinoma and its
      various histological patterns. Most tumors are well differentiated. All patients
      included in this study were diagnosed with adenocarcinoma of the esogastric
      junction through prior endoscopy and histopathological examination of the
      biopsies. Patients with resectable tumors underwent surgical resection followed
      by histopathological examination of the resected samples. The most frequently
      encountered tumor was represented by type III, subcardial adenocarcinoma in 68%
      of all cases. The main surgical procedure was distal esophagectomy with total
      gastrectomy extended by abdominal transthoracic approach. All the studied cases
      were diagnosed with adenocarcinoma of the gastro-esophageal junction. The
      majority of them were well-differentiated being easily recognized by their
      submucosal invasion. We believe that surgery with curative intent is superior to
      curative palliative treatment.

PMID- 22395507
TI  - Immunologic and cytogenetic markers expressed in non-Hodgkin lymphoma of head and
      neck.
AB  - Very often, the first doctor who examines a patient with malignant lymphoma is an
      ENT specialist, because non-Hodgkin lymphoma is five times more frequent than
      Hodgkin disease in the head and neck region. Approximately 25% of extranodal
      lymphoma occurs in the head and neck and extranodal presentation is twice as
      frequent as nodal presentation. This paper present a study of the patients from
      ENT, Head & Neck Surgery Clinic of Coltea Clinical Hospital, Bucharest, Romania,
      diagnosed with malignant lymphoma. We developed a specific scheme for collecting
      data about patients, together with pathology details, immunology and cytogenetic
      markers. We tried to establish a relation between immunologic and cytogenetic
      markers and the clinical evolution of non-Hodgkin lymphoma. For this study, we
      analyzed data regarding CD10, CD5, CD20, Bcl-2, Bcl-6, Ki67 expression obtained
      from 58 patients with follicular lymphoma. An attempt was made to correlate the
      presence of certain immunohistochemical and cytogenetic markers with the
      evolution and aggressiveness of the disease, and we can say that Bcl-2 is
      positive in all tumor subtypes, being associated relatively frequently with CD5
      expression, and is a marker of poor prognosis, while Bcl-6 is positive especially
      in the tumor forms associated with the predominance of small cells and is a
      marker of favorable prognosis.

PMID- 22395508
TI  - P53, Bcl-2 and Ki67 immunoexpression in follicular solid ameloblastomas.
AB  - The study included a total of 17 ameloblastomas diagnosed in a range of 15 years.
      Clinical data processing was followed by histopathological and
      immunohistochemical analysis, following the expression of p53, Bcl-2 and Ki67 in
      the tumor epithelial compartments. Lesions predominated in the age range 20-40
      years, to male gender, being located mainly in the mandible (88.2%). Typical
      follicular ameloblastoma was present in 70.6% of analyzed tumors. P53 and Bcl-2
      immunoexpression was identified especially in the peripheral cells, the number of
      marked cells being over 50%, while the percentage of positive cells from the
      stellate reticulum was below 10%. The Ki67 positivity index was below 10% in both
      compartments. Squamous and granular cells reveal no stain for the investigated
      markers. Peripheral columnar cells are active compartment of ameloblastomas being
      involved in the processes of proliferation-apoptosis.

PMID- 22395509
TI  - Healing process and laser therapy in the superficial periodontium: a histological
      study.
AB  - AIM: To evaluate the efficiency of laser therapy in healing, regeneration and
      repair processes located in the superficial periodontium after gingivectomy
      procedures. MATERIALS AND METHODS: The study group consisted of 38 patients
      without any systemic diseases presenting with gingival hypertrophy developed
      exclusively within the clinical context of gingivitis and/or periodontitis. All
      patients were included in the study based on their informed consent. All patients
      required several surgical interventions at the level of the superficial
      periodontium. Subgroup 1 (17 patients) was treated only through gingivectomy
      procedures. For subgroup 2 (21 patients), the gingivectomy was associated with
      laser therapy, applied every day for seven days. Gingival mucosa fragments were
      taken on day 1 (curative gingivectomy) and on day 21 (clinical control and
      corrective gingivectomy), and routinely processed for the microscopic exam, using
      Hematoxylin-Eosin and special stains (trichrome Szekely and Periodic Acid
      Schiff). RESULTS AND DISCUSSION: The comparison between the morphological
      pictures characterizing the healing process associated or not with laser therapy,
      allowed the identification of some features supporting the benefits of laser
      therapy. We believe that the decrease in the inflammatory infiltrate located in
      the lamina propria is the critical morphological trait for the control of a
      healing process as near to restitutio ad integrum as possible. The diminished
      number of lymphocytes and macrophages will implicitly determine a lower
      production of chemical mediators interfering with the sequences of the healing
      process. CONCLUSIONS: The morphological differences identified at the gingival
      epithelium level and subjacent lamina propria support the value of laser therapy,
      stimulating an improved healing of the damaged tissues.

PMID- 22395510
TI  - Morphofunctional aspects of lower limb in multiple sclerosis.
AB  - Gait, as an expression of the locomotive system, needs a complex biomechanical
      analysis, which allows the description of multiple sclerosis (MS) specific
      patterns, MS patients having a polymorphism of motion patterns. The studied group
      consisted of 13 MS patients with gait disorders, average age of the group was of
      36 years. The evaluation of the subjects comprises: clinical evaluation
      (anamnesis, neurological examination), paraclinical evaluation (MRI), functional
      evaluation, neuro-physiologic evaluation and biomechanical evaluation.
      Biomechanical examination was completed using the force and pressure-measuring
      platform of plantar pressure distribution Footscan Scientific Version, RSscan.
      The studied parameters were: contact area, active contact area, heel rotation,
      foot balance, foot angle. The evaluated zones during a gait cycle were: the heel,
      medial foot, antefoot. Although the analysis of contact area in the lateral foot
      did not show any significant differences between the right and the left foot, it
      nonetheless underlined a major difference in the expression of maximum and
      minimum values, which meant that MS patients with clinically detectable gait
      disorders had a tendency to increase contact area to maintain balance. Examining
      the foot positions in relation to the movement direction and to the foot vertical
      axis, we noticed the existence of certain elements indicating an orientation
      tendency of the foot. This tendency had to be related to neutral position
      (corresponding to anatomical position) of the foot. We also noticed a foot
      deviation in abduction, associated with visible pronation and decrease of the
      contact area corresponding to medial plantar zone.

PMID- 22395511
TI  - Morphological study of bronchial mucosa in the chronic obstructive pulmonary
      disease under the influence of therapeutic algorithm.
AB  - OBJECTIVES: Immunohistochemical evaluation of the effectiveness of bronchodilator
      treatment in patients with chronic obstructive pulmonary disease (COPD).
      MATERIALS AND METHODS: There have been examined bronchial mucosa biopsies taken
      endoscopically from 18 patients with obstructive pulmonary disease. The biopsies
      were fixed in 4% buffered formalin for 24-48 hours and paraffin inclusion was
      made using the standard technique. For each biopsy, there were performed 10
      serial sections with a thickness of 5 MUm. The sections were stained using
      morphological, histochemical and immunohistochemical methods. At three of the
      cases, the paraffin blocks were reconverted for the electron microscopy study, in
      order to assess subcellular details, with special reference to "target" cells
      involved in local immune response. Morphohistochemical and immunohistochemical
      analysis was effectuated on biopsies removed before and after the treatment with
      bronchodilators. RESULTS: The analysis of the biopsies removed before treatment
      revealed the following aspects: degenerative alterations of the surface
      epithelium, loss of ciliary differentiation, absence of caliciform cells,
      hyperexfoliation, formation of pseudopapillary structures, degenerative lesions
      of the glands, mucoid and oncocytary metaplasia, stasis in the dilated blood
      vessels, partly hyalinized wall, multiforme chronic inflammatory infiltrate,
      myofibroblasts in the depth of lamina propria; argyrophilic basement membrane,
      fragmentation and lysis of elastic fibers, degranulated mast cells associated
      with inflammatory infiltrate, with electron-dense typical granules, inflammatory
      infiltrate with CD20 positive B-lymphocytes, arranged perivasculary and in the
      vicinity of the basement membrane; rare positive CD4 T-lymphocytes; reduced
      number of plasma cells. After treatment we found the following aspects: partial
      or complete regeneration of the covering epithelium, with the presence of cilia
      cells and occasionally of caliciform cells; remaining myofibroblastic reaction in
      the lamina propria; increased number of mast cells with minimal or no
      degranulation; immature, lamelled mast cells. CONCLUSIONS: The application of
      management principles in group therapy study was done by the study which aims to
      demonstrate the beneficial role in COPD therapy of combining a beta2-agonist with
      an anticholinergic, obtaining in this way an additional bronchodilator effect,
      compared with the one obtained by administrating bronchodilators of type beta2
      agonists. Deepening the molecular and cellular mechanisms of COPD can lead to
      more effective methods for early detection of disease, pharmacotherapy targeted
      and effective conduct exacerbations.

PMID- 22395512
TI  - Vascular and mesenchymal factors during heart development: a chronological study.
AB  - As heart development is an incomplete described area, and likewise an important
      source of intra- and post-partum morbidity and mortality, we have aimed at
      analyzing both vascular and cytoskeletal factors during early heart development
      in humans. The distribution of CD105, CD31, alpha-SMA, vimentin and desmin have
      been studied on a series of normal human heart tissues varying between five and
      33 weeks of gestational age, utilizing both enzymatic single
      immunohistochemistry, as well as double immunofluorescence. We showed here that
      CD105 is already expressed at five weeks of gestational age in the future
      endocardium, and that between 9 and 10 weeks it shows clear-cut formed vessels.
      CD31 was also present diffusely at five weeks in the myocardium, while beginning
      with seven weeks, endocardium and vessels were clearly positive. Contrary to what
      it might be expected for striated muscle cells, cardiomyocytes were alpha-SMA
      positive between 9 and 20 weeks, a time window during which the marker showed
      clear-cut sarcomer formation. Desmin was first detected at nine weeks lining the
      cardiomyocyte plasma membrane, and after 17 weeks it showed the adult-like
      striated pattern of the protein. As expected, vimentin was already present in the
      mesenchymal cells from the first investigated time point, retaining a
      perivascular localization only towards higher ages. This is the first study that
      describes these vascular, muscular and mesenchymal factors on a large series of
      sequential human tissues, in an attempt to shed more light on the development of
      heart.

PMID- 22395513
TI  - The involvement of TGF-beta1 and CTGF in regional gingival overgrowth.
AB  - Gingival overgrowth is a multifactorial and invalidating condition. Our research
      is about gingival overgrowth caused by gingival plaque, its purpose being the
      evaluation of the presence of gingivitis and/or parodontitis in patients with
      gingival growth and the extent in which there is a connection between gingival
      overgrowth and the inflammatory process that can contribute to an exceedingly
      stimulation of the overgrowth. Immunohistological study was conducted on human
      material--gingival mucosa that came from patients with ages between 20-65 years,
      divided into three groups: group I--control group, group II--patients with
      gingivitis, group III--patients with local or general periodontitis. The
      intensity of immunohistochemical staining of TGF-beta1 and CTGF varies from one
      group to another, and also depends on the area of gingival mucosa that was
      observed. TGF-beta1 has a crucial role in periodontal disease fibrogenesis by
      intensifying the action of CTGF.

PMID- 22395514
TI  - Comparative analysis of different surgical procedures for female stress urinary
      incontinence. Is stem cell implantation the future?
AB  - RATIONALE: Stress urinary incontinence (SUI) represents a major public health
      problem and although there are many treatments available, only a few can restore
      the anatomical background of this disorder. Injections of stem cells into the
      middle urethra have the possibility of restoring the contractility of the
      striated muscles and rhabdosphincters. The aim of stem cell therapy is to
      replace, repair or enhance the biological function of damaged tissue or organs.
      OBJECTIVE: Assessing the latest minimally invasive procedures of intra and
      perisphincterian injection of autologous stem cells and to compare the urodynamic
      results at one year after different surgical procedures for genuine stress
      urinary incontinence by measuring their impact on urinary flow rate (Qmax) and
      bladder pressure at Qmax during micturition. METHODS AND RESULTS: On October 18,
      2010, in "Fundeni" Clinic of Urology and Renal Transplantation we performed for
      the first time in Romania, stem cell implantation in the urethral sphincter in
      four patients with stress urinary incontinence and compared the results of the
      urodynamic investigations of female patients operated with pure SUI with other
      surgical techniques. The analyzed procedures were: Burch colposuspension (11
      cases), TVT-like (IVS sling in 26 cases), TOT-like (CYSTO-SWING sling in 41
      cases). Followed variables were: Qmax, Pves at Qmax, postvoiding residual (PVR).
      Clinical examination and voiding diary in six weeks after the surgery revealed a
      decrease of urine loss with an improvement of the patient' quality of life
      according to visual analogue scale. For female patients with myoblasts implant,
      changes in Qmax and Pves at Qmax were minimal and statistically insignificant in
      the context of inclusion criteria, but we noticed a trend of minimal change in
      these urodynamic characteristics, namely, an average decrease of Qmax with 2.1
      mL/s and an average increase of Pves at Qmax with 0.6 cmH(2)O. CONCLUSIONS: The
      development of myoblasts implant (if they will pass the time-proof test) could
      represent a breakthrough in treating this condition. As the pathogenesis of SUI
      is better understood and the development of tissue engineering technology
      advances, tissue engineering will play a more important role in the treatment of
      patients with SUI.

PMID- 22395515
TI  - Molecular characterization of apoptosis by the immunohistochemical evaluation of
      Bcl-2 in breast cancer.
AB  - PURPOSE: Immunohistochemical markers are used to classify breast cancer into
      molecular subtypes biologically and behavior distinct. The Bcl-2 gene has been
      implicated in a number of cancers and it is also thought to be involved in
      resistance to conventional cancer treatment. The aim of this study was to
      investigate apoptosis in breast cancer cells and in molecular groups using IHC
      expression of Bcl-2. MATERIALS AND METHODS: Our study included 61 patients that
      been followed up five years since diagnosis. The traditional prognostic factors:
      age, tumor size, histological type, histological grade, clinical stage and the
      status of the lymph nodes were used for primary morphological evaluation.
      Molecular classification of cases and Bcl-2 assessment was performed by
      immunohistochemistry in agreement with data from the literature. RESULTS: More
      than an half of tumors were positive for Bcl-2 showing a favorable response to
      endocrine therapy. The average age of the patients, hormonal status, tumoral
      diameter and histological grade showed significant differences statistically.
      Most of positive cases for Bcl-2 belong to the luminal tumor group, while non
      luminal tumors have a negative reaction. When we compared well-known histological
      types, we noticed insignificant issues regarding score groups for Bcl-2; in
      exchange, when they were compared into molecular groups, we obtained the
      strongest statistical correlation. CONCLUSIONS: Assessment of apoptosis by Bcl-2
      leads to the identification of molecular groups with different
      immunohistochemical and clinical features and different survival rates, better
      for Bcl-2 positive tumors and worse in Bcl-2 negative tumors.

PMID- 22395516
TI  - Collagen IV and MMP-9 expression in hypertrophic gingiva during orthodontic
      treatment.
AB  - INTRODUCTION: In the present study, we aimed to assess MMP-9 and type IV collagen
      in the gingival tissue in patients with gingival overgrowth (GO) after
      orthodontic treatment, with or without clinical signs of inflammation to
      appreciate the role of balance between those two markers in the onset of GO
      during tooth movement. MATERIALS: Gingival tissue was harvested from 45 patients
      divided in three groups: 15 patients with orthodontic appliance that developed GO
      on at least two teeth; 15 patients with chronic gingivitis with GO; 15 patients
      (control group) with healthy periodontal tissues, without clinical gingival
      changes, in whom the first premolar was planned for extraction for orthodontic
      purposes (canine distalization). METHODS: The tissue samples obtained by
      gingivectomy were fixed in 10% neutral formalin solution for 48 hours and then
      included in paraffin with the usual technique. The histologic examination was
      performed using classic Hematoxylin-Eosin technique. Double immunofluorescence
      was performed for anti-MMP-9 and anti-collagen IV antibodies. RESULTS: MMP
      9/collagen IV double stainings showed an increase of fibrosis and inflammation in
      different degrees. CONCLUSIONS: The mechanical stress induced by the orthodontic
      devices, might be the key players in driving both the inflammation and the
      fibrotic reaction.

PMID- 22395517
TI  - Rare renal tumor--mucinous tubular and spindle cell carcinoma.
AB  - We report a rare case of renal tumor--mucinous tubular and spindle cell carcinoma
      in a 65-year-old man. The tumor, located in the right kidney, was well
      circumscribed. Microscopically, the tumoral proliferation was composed of
      cuboidal cells arranged in tubules, with abrupt transition to spindle cell
      morphology in a myxoid stroma. Because of the favorable prognosis with this type
      of tumor, mucinous tubular and spindle cell carcinoma must be differentiated from
      papillary renal cell carcinoma, especially the variant with sarcomatoid
      dedifferentiation.

PMID- 22395518
TI  - Pulmonary alveolar lipoproteinosis associated with emphysematous areas.
AB  - Pulmonary alveolar lipoproteinosis, described for the first time in 1958 by Rosen
      SH, Castleman B and Liebow AA, is a rare pathological condition characterized by
      alveolar accumulation of lipoproteinaceous material. It is the result of
      macrophages impairment to rid the alveolar spaces of spent surfactant. This
      condition involves a restrictive function of pulmonary tissue, reflected in gas
      exchange impairment and respiratory symptoms of variable severity. Until now,
      about 410 cases have been reported in the literature. From these cases, 90% were
      represented by primary type of pulmonary alveolar lipoproteinosis. We present the
      case of 37-year-old male patient admitted in the Department of Internal Medicine,
      Emergency County Hospital, Constanta, Romania, with progressive exertional
      dyspnea, dry cough and perioral cyanosis. The clinical symptoms started three
      months before hospital admission. Based on clinical findings and imaging
      features, the primary pulmonary alveolar proteinosis diagnosis has been
      suspected. Uncharacteristic serous aspect of fluid resulting from bronchoalveolar
      lavage required open lung biopsy. Pathologic examination of pulmonary slice
      revealed features consistent with the diagnosis of pulmonary alveolar
      lipoproteinosis associated with emphysematous foci. The peculiarity of this case
      lies in the association of two pathological conditions, each of them requiring
      different pathways.

PMID- 22395519
TI  - Mandibular ameloblastic carcinoma in a young patient.
AB  - Ameloblastic carcinoma is a rare cause of jaw tumors, especially in children.
      This rare, rapidly growing, malignant tumor of odontogenic origin affects
      predominantly the mandible and maxilla. Hypercellularity, lack of
      differentiation, high mitotic index, vascular and neural invasion are its main
      histological features. Local destruction and distant metastases to the lungs,
      bones, liver and brain are common in ameloblastic carcinoma. Prognosis is poor,
      due to its low sensitivity to chemo- and radiotherapy. We report the case of an 8
      year-old girl with ameloblastic carcinoma of the left mandible and extensive
      right pleuro-pulmonary and bone marrow metastases. Biopsies made from the
      mandibular tumor and lung tumor tissue obtained by bronchoscopy, showed the same
      histological features, that of ameloblastic carcinoma. Diagnostic and treatment
      challenges are shown in this uncommon pediatric solid tumor of the jaw.
      Carboplatin and etoposide treatment showed some therapeutic effect upon the
      primary tumor, but lung infiltrations were not influenced. Palliative treatment
      was initiated. Early detection of ameloblastic carcinoma, before massive distant
      metastases develop would be an option for long-term survival, which can be
      achieved with radical surgery followed by radiotherapy.

PMID- 22395520
TI  - Bilateral extensor indicis brevis: a rare muscular variant.
AB  - Variants on muscles and tendons of the forearm or hand occur frequently in human
      beings. They are often discovered during educational cadaveric dissections and
      surgical procedures. Knowledge of such anomalies is necessary to the surgeons in
      order to avoid possible damage to adjacent muscles' tendons' blood vessels or
      nerves. Here we describe a rare muscular variant, the extensor indicis brevis
      originating from the ligaments of the proximal row of dorsal carpal bones.

PMID- 22395521
TI  - Conjoined human oocytes observed during assisted reproduction: description of
      three cases and review of the literature.
AB  - Conjoined oocytes derived from binovular follicles have been suspected to play a
      role in producing dizygotic twins, mosaicism, tetraploidy or chimeras. This issue
      is discussed by presenting three examples for conjoined oocytes observed in our
      programme of human assisted reproduction and by including a review of
      corresponding cases. Our material comprises two associated immature oocytes and
      two cases in which an immature oocyte was attached to a mature oocyte. One of the
      mature oocytes was fertilized and transferred after cleavage without resulting in
      pregnancy. In the literature, another fifteen descriptions of conjoined oocytes
      were found. Here, simultaneous fertilization of both gametes occurred only once
      and there was no evidence for pregnancies arising from binovular follicles. These
      data suggest that binovular follicles do not cause dizygotic twins or genetic
      abnormalities.

PMID- 22395522
TI  - Synchronous intestinal tumors: aggressive jejunal carcinoid and sigmoid malignant
      polyp.
AB  - Association of aggressive jejunal carcinoid tumors and other primary
      gastrointestinal neoplasms are rarely observed. We describe the case of a
      synchronous jejunal carcinoid tumor and two colorectal polyps in a 78-year old
      woman. Surgical intervention was performed for the colorectal tumors and the
      carcinoid was incidentally found. It was well differentiated but was accompanied
      by lymph node metastasis and peritoneal carcinomatosis. In this case, the
      prognosis was not depending by the colorectal tumors but the aggressive feature
      of jejunal carcinoid lead to patient's death.

PMID- 22395523
TI  - Systemic mastocytosis associated with essential thrombocythemia.
AB  - Mastocytosis comprises a spectrum of disorders characterized by abnormal growth
      of mast cells (MS). Four entities are recognizable according to WHO
      classification. Association of systemic mastocytosis (SM) with a chronic
      myeloproliferative neoplasia (SM-AHNMD) is the second frequently category.
      Published descriptions of the clinicopathologic features of SM-AHNMD are largely
      limited to individual case reports. We present the case of a 41-year-old woman
      with thrombocytosis and mild splenomegaly. Clinical suspicion was of chronic
      myeloproliferative neoplasia (CMN). Bone marrow trephine biopsy examination
      (histology and immunohistochemistry for CD117 and CD25) revealed a SM associated
      with CMN, essential thrombocythemia (ET) type. The JAK2 V617F (for CMN) was
      detected but KIT/Asp816Val (reported in ~80% of SM) was absent. We discussed the
      particularity of the cases correlated with a review of the literature.

PMID- 22395524
TI  - Carnitine deficiency.
AB  - We present the case of a female patient, aged 12 years, with fatigability and
      exertional myalgias, progressively developed within the last two years. Negative
      family history, as well as negative personal medical history, were found. At
      physical examination, short stature, proximal muscle weakness and mild
      hepatomegaly were noted. Urine ketones level was slightly decreased, serum
      transaminases, creatine kinase and lactate dehydrogenase levels were increased.
      Electromyographical examination showed a myopathic non-specific pattern. Deltoid
      muscle biopsy revealed: small, clear vesicles are present on Hematoxylin-Eosin
      and modified Gomori trichrome stains; modified Gomori trichrome stain also
      revealed muscle fibers (especially type I of muscle fibers) having mild to
      moderate mitochondrial proliferation (red rim and speckled sarcoplasm). The lipid
      storage has been well demonstrated by Sudan Black stain, which revealed small
      lipid droplets in type I muscle fibers. Abnormal internal architecture with a
      punctate pattern was showed by adenine dinucleotide tetrazolium reductase and
      succinate dehydrogenase stains. Electron microscopy showed small inter
      myofibrillar accumulations of round, amorphous, homogeneous acellular substances
      that are not membrane bounded. These features indicate that these are neutral fat
      (lipid) droplets. Subsarcolemmal accumulations of mitochondria were also
      revealed. The differential diagnosis of this case is discussed, and the up to
      date general data concerning carnitine deficiency are presented. The aim of our
      case-report is to emphasize the role of muscle biopsy in carnitine deficiency, as
      well as to remind the necessity of keeping in mind such metabolic disorders when
      doing the differential diagnostic of a muscular weakness.

PMID- 22395525
TI  - Plasmonic Ag/AgBr nanohybrid: synergistic effect of SPR with photographic
      sensitivity for enhanced photocatalytic activity and stability.
AB  - A plasmonic Ag/AgBr nanohybrid has been synthesized by in situ thermal reduction
      of AgBr nanoparticles in polyols. This directly converted Ag/AgBr shows
      significant absorption over the full visible spectrum. The enhanced light
      absorption in the spectral region of 450 nm to 800 nm was due to the plasmonic
      nanosized Ag grown on the surface of AgBr nanoparticles with mixed morphologies
      and increased sizes. Under visible light irradiation, the plasmonic Ag/AgBr
      exhibits high activity and stability for the photodegradation of organic
      pollutants, e.g. methylene blue. The contribution of the SPR and its synergistic
      effect with the photosensitive AgBr in the photocatalytic activity were verified.
      Based on the plasmon-mediated charge injection and the band structure of the
      metal-semiconductor heterojunction, a mechanism of the plasmon synergistically
      enhanced photocatalytic process was proposed.

PMID- 22395526
TI  - Association between two polymorphisms in the HLA-G gene and angiographic coronary
      artery disease.
AB  - Atherosclerosis and related complications still represent the major cause of
      morbidity and mortality in industrialized countries. Therefore, it is
      particularly important to investigate the molecules involved in cardiac
      inflammation. Evidence exists showing that the human leukocyte antigen-G (HLA-G)
      gene tissue expression and related protein physiological significance is
      influenced by two polymorphisms, rs16375 and rs1632933. In this study, allelic,
      genotypic and haplotypic frequencies of a 14-bp insertion/deletion (Ins/Del)
      (rs16375) and of rs1632933 polymorphisms of the HLA-G gene were investigated in
      664 patients with coronary artery disease (CAD) and 345 matched controls by
      polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis
      and real-time PCR. The frequency of the Ins/Ins genotype was significantly higher
      in patients with CAD compared to the controls (P=0.018). After analysis of
      confounding variables, the results showed that the homozygous Ins/Ins was
      significantly and independently associated with the presence of angiographic CAD
      (odds ratio 2.09, 95% confidence interval 1.10-4.02, P=0.03). Our data
      demonstrate a new risk factor for this multifactorial inflammatory disease.

PMID- 22395527
TI  - Long-term safety and tolerability of lurasidone in schizophrenia:  a 12-month,
      double-blind, active-controlled study.
AB  - The aim of this study is to evaluate the long-term safety and tolerability of
      lurasidone in the treatment of schizophrenia. Clinically stable adult outpatients
      with schizophrenia were randomized in a 2 : 1 ratio to 12 months of double-blind
      treatment with once-daily, flexibly-dosed lurasidone (40-120 mg) or risperidone
      (2-6 mg). Outcome measures included adverse events (AEs), vital signs, ECG, and
      laboratory tests. Secondary assessments included measures of psychopathology. A
      total of 427 patients were randomized to treatment with lurasidone and 202 with
      risperidone. The three most frequent AEs in the lurasidone group (vs.
      risperidone) were nausea (16.7 vs. 10.9%), insomnia (15.8 vs. 13.4%), and
      sedation (14.6 vs. 13.9%); the three most frequent AEs in the risperidone group
      (vs. lurasidone) were increased weight (19.8 vs. 9.3%), somnolence (17.8 vs.
      13.6%), and headache (14.9 vs. 10.0%). A higher proportion of patients receiving
      risperidone had at least a 7% endpoint increase in weight (14 vs. 7%). The median
      endpoint change in prolactin was significantly higher for risperidone (P<0.001).
      A comparable improvement in efficacy measures was observed with both agents and
      the rates of relapse were similar. All-cause discontinuation rates were higher
      for lurasidone versus risperidone. Long-term treatment with lurasidone was
      generally well tolerated in this study, with minimal effects on weight and
      metabolic outcomes.

PMID- 22395529
TI  - Long-term correction of very long-chain acyl-coA dehydrogenase deficiency in mice
      using AAV9 gene therapy.
AB  - Very long-chain acyl-coA dehydrogenase (VLCAD) is the rate-limiting step in
      mitochondrial fatty acid oxidation. VLCAD-deficient mice and patients clinical
      symptoms stem from not only an energy deficiency but also long-chain metabolite
      accumulations. VLCAD-deficient mice were treated systemically with 1 * 10(12)
      vector genomes of recombinant adeno-associated virus 9 (rAAV9)-VLCAD. Biochemical
      correction was observed in vector-treated mice beginning 2 weeks postinjection,
      as characterized by a significant drop in long-chain fatty acyl accumulates in
      whole blood after an overnight fast. Changes persisted through the termination
      point around 20 weeks postinjection. Magnetic resonance spectroscopy (MRS) and
      tandem mass spectrometry (MS/MS) revealed normalization of intramuscular lipids
      in treated animals. Correction was not observed in liver tissue extracts, but
      cardiac muscle extracts showed significant reduction of long-chain metabolites.
      Disease-specific phenotypes were characterized, including thermoregulation and
      maintenance of euglycemia after a fasting cold challenge. Internal body
      temperatures of untreated VLCAD(-/-) mice dropped below 20  degrees C and the
      mice became lethargic, requiring euthanasia. In contrast, all rAAV9-treated
      VLCAD(-/-) mice and the wild-type controls maintained body temperatures. rAAV9
      treated VLCAD(-/-) mice maintained euglycemia, whereas untreated VLCAD(-/-) mice
      suffered hypoglycemia following a fasting cold challenge. These promising results
      suggest rAAV9 gene therapy as a potential treatment for VLCAD deficiency in
      humans.

PMID- 22395530
TI  - miR-29 inhibits bleomycin-induced pulmonary fibrosis in mice.
AB  - Loss of microRNA-29 (miR-29) is known to be a mechanism of transforming growth
      factor-beta (TGF-beta)-mediated pulmonary fibrosis, but the therapeutic
      implication of miR-29 for pulmonary fibrosis remains unexplored. The present
      study investigated whether miR-29 had therapeutic potential for lung disease
      induced by bleomycin in mice. In addition, the signaling mechanisms that
      regulated miR-29 expression were investigated in vivo and in vitro. We found that
      miR-29 was a downstream target gene of Smad3 and negatively regulated by TGF
      beta/Smad signaling in fibrosis. This was evidenced by the findings that mice or
      pulmonary fibroblasts null for Smad3 were protected against bleomycin or TGF
      beta1-induced loss of miR-29 along with fibrosis in vivo and in vitro.
      Interestingly, overexpression of miR-29 could in turn negatively regulated TGF
      beta and connective tissue growth factor (CTGF) expression and Smad3 signaling.
      Therefore, Sleeping Beauty (SB)-mediated miR-29 gene transfer into normal and
      diseased lung tissues was capable of preventing and treating pulmonary fibrosis
      including inflammatory macrophage infiltration induced by bleomycin in mice. In
      conclusion, miR-29 is negatively regulated by TGF-beta/Smad3 and has a
      therapeutic potential for pulmonary fibrosis. SB-mediated miR-29 gene therapy is
      a non-invasive therapeutic strategy for lung disease associated with fibrosis.

PMID- 22395528
TI  - Stem cells and regenerative medicine in lung biology and diseases.
AB  - A number of novel approaches for repair and regeneration of injured lung have
      developed over the past several years. These include a better understanding of
      endogenous stem and progenitor cells in the lung that can function in reparative
      capacity as well as extensive exploration of the potential efficacy of
      administering exogenous stem or progenitor cells to function in lung repair.
      Recent advances in ex vivo lung engineering have also been increasingly applied
      to the lung. The current status of these approaches as well as initial clinical
      trials of cell therapies for lung diseases are reviewed below.

PMID- 22395532
TI  - Differences in activity level between cownose rays (Rhinoptera bonasus) and
      Atlantic stingrays (Dasyatis sabina) are related to differences in heart mass,
      hemoglobin concentration, and gill surface area.
AB  - Aquatic animals are faced with the challenge of extracting oxygen from water, a
      medium that is metabolically expensive to ventilate and that contains just a
      fraction of the oxygen concentration relative to air, yet the physiologies of
      fishes have evolved to support a wide range of activity levels in nature. Oxygen
      delivery components, including gill surface area (oxygen uptake), blood chemistry
      (oxygen transport), and the heart (system pump), have been positively correlated
      to activity level in teleost fishes, yet relatively little is known about how
      these components are related to activity in elasmobranches. The current study
      addresses this question by examining heart mass, hemoglobin concentration,
      hematocrit level, and gill surface area in wild-caught representatives of the
      benthic Atlantic stingray (Dasyatis sabina) and active cownose ray (Rhinoptera
      bonasus). Allometric scaling exponents are similar for all four measures between
      the study species. Heart mass, gill surfaces areas, and hemoglobin concentrations
      were 2.1 times, approximately 7.1 times, and 2.0 times higher, respectively, in
      active cownose rays, when compared to benthic Atlantic stingrays, after
      correcting for differences in body mass. When considered in the context of
      functional plasticity within the oxygen delivery systems of benthic and active
      species, data from the current study indicate that higher activity levels in
      cownose rays are supported by modifications that, at least in part, are likely to
      enhance oxygen uptake.

PMID- 22395531
TI  - Neonatal gene therapy with a gamma retroviral vector in mucopolysaccharidosis VI
      cats.
AB  - Mucopolysaccharidosis (MPS) VI is due to a deficiency in the activity of N
      acetylgalactosamine 4-sulfatase (4S), also known as arylsulfatase B. Previously,
      retroviral vector (RV)-mediated neonatal gene therapy reduced the clinical
      manifestations of MPS I and MPS VII in mice and dogs. However, sulfatases require
      post-translational modification by sulfatase-modifying factors. MPS VI cats were
      injected intravenously (i.v.) with a gamma RV-expressing feline 4S, resulting in
      5 +/- 3 copies of RV per 100 cells in liver. Liver and serum 4S activity were
      1,450 +/- 1,720 U/mg (26-fold normal) and 107 +/- 60 U/ml (13-fold normal),
      respectively, and were directly proportional to the liver 4S protein levels for
      individual cats. This study suggests that sulfatase-modifying factor (SUMF)
      activity in liver was sufficient to result in active enzyme despite
      overexpression of 4S. RV-treated MPS VI cats achieved higher body weights and
      longer appendicular skeleton lengths, had reduced articular cartilage erosion,
      and reduced aortic valve thickening and aortic dilatation compared with untreated
      MPS VI cats, although cervical vertebral bone lengths were not improved. This
      demonstrates that therapeutic expression of a functional sulfatase protein can be
      achieved with neonatal gene therapy using a gamma RV, but some aspects of bone
      disease remain difficult to treat.

PMID- 22395535
TI  - Aluminum ammonium sulfate dodecahydrate purified from traditional Chinese
      medicinal herb Korean monkshood root is a potent matrix metalloproteinase
      inhibitor.
AB  - Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases and key
      regulators for many physiological and pathological functions. The MMP inhibitors
      have been shown to modulate diseases such as cancer, inflammation, and
      cardiovascular diseases. In this paper we tracked the MMP inhibitory activities
      of the traditional Chinese medicinal herb Korean Monkshood Root. The purified
      active ingredient was identified by the elemental analysis, infrared spectrum
      (IR) and X-ray diffraction as aluminum ammonium sulfate dodecahydrate. This
      inorganic compound showed inhibitory activities toward a number of MMP family
      members. In particular, it has a strong inhibitory effect toward MMP-2 and MMP-9,
      with IC50 values of 0.54 and 0.50 MUM, respectively. Further analysis suggested
      that the MMP inhibitory activity is mainly due to Al(3+). Cell viability assays
      using human fibrosarcoma HT1080 cells showed aluminum ammonium sulfate had
      minimal cyto-toxicity with a concentration up to 500 MUM. However, within 50 MUM,
      it exhibited significant inhibition of cell invasion. To our knowledge, there has
      been no previous report of inorganic form of the MMP inhibitor with strong
      inhibitory activity. Our results for the first time showed that aluminum ammonium
      sulfate is an inorganic form of MMP inhibitor with high potency, and can be used
      to interfere with MMP related cellular processes.

PMID- 22395533
TI  - Motor-driven bacterial flagella and buckling instabilities.
AB  - Many types of bacteria swim by rotating a bundle of helical filaments also called
      flagella. Each filament is driven by a rotary motor and a very flexible hook
      transmits the motor torque to the filament. We model it by discretizing
      Kirchhoff's elastic-rod theory and develop a coarse-grained approach for driving
      the helical filament by a motor torque. A rotating flagellum generates a thrust
      force, which pushes the cell body forward and which increases with the motor
      torque. We fix the rotating flagellum in space and show that it buckles under the
      thrust force at a critical motor torque. Buckling becomes visible as a
      supercritical Hopf bifurcation in the thrust force. A second buckling transition
      occurs at an even higher motor torque. We attach the flagellum to a spherical
      cell body and also observe the first buckling transition during locomotion. By
      changing the size of the cell body, we vary the necessary thrust force and
      thereby obtain a characteristic relation between the critical thrust force and
      motor torque. We present a elaborate analytical model for the buckling transition
      based on a helical rod which quantitatively reproduces the critical force-torque
      relation. Real values for motor torque, cell body size, and the geometry of the
      helical filament suggest that buckling should occur in single bacterial flagella.
      We also find that the orientation of pulling flagella along the driving torque is
      not stable and comment on the biological relevance for marine bacteria.

PMID- 22395536
TI  - A new single chamber implantable defibrillator with atrial sensing: a practical
      demonstration of sensing and  ease of implantation.
AB  - Implantable cardioverter-defibrillators (ICDs) terminate ventricular tachycardia
      (VT) and ventricular fibrillation (VF) with high efficacy and can protect
      patients from sudden cardiac death (SCD). However, inappropriate shocks may occur
      if tachycardias are misdiagnosed. Inappropriate shocks are harmful and impair
      patient quality of life. The risk of inappropriate therapy increases with lower
      detection rates programmed in the ICD.  Single-chamber detection poses greater
      risks for misdiagnosis when compared with dual-chamber devices that have the
      benefit of additional atrial information. However, using a dual-chamber device
      merely for the sake of detection is generally not accepted, since the risks
      associated with the second electrode may outweigh the benefits of detection.
      Therefore, BIOTRONIK developed a ventricular lead called the Linox(SMART) S DX,
      which allows for the detection of atrial signals from two electrodes positioned
      at the atrial part of the ventricular electrode. This device contains two ring
      electrodes; one that contacts the atrial wall at the junction of the superior
      vena cava (SVC) and one positioned at the free floating part of the electrode in
      the atrium. The excellent signal quality can only be achieved by a special filter
      setting in the ICD (Lumax 540 and 740 VR-T DX, BIOTRONIK). Here, the ease of
      implantation of the system will be demonstrated.

PMID- 22395537
TI  - Developmental changes in human dural innervation.
AB  - INTRODUCTION: There is limited published work on the abundant innervation of the
      human dura mater, its role and responses to injury in humans. The dura not only
      provides mechanical support for the brain but may also have other functions,
      including control of the outflow of venous blood from the brain via the dural
      sinuses. The trigeminal nerve supplies sensory fibres to the dura as well as the
      leptomeninges, intracranial blood vessels, face, nose and mouth. Its relatively
      large size in embryonic life suggests an importance in development; the earliest
      fetal reflexes, mediated by the trigeminal, are seen by 8 weeks. Trigeminal
      functions vital to the fetus include the coordination of sucking and swallowing
      and the protective oxygen-conserving reflexes. Like other parts of the nervous
      system, the trigeminal undergoes pruning and remodelling throughout development.
      METHODS: We have investigated changes in the innervation of the human dura with
      age in 27 individuals aged between 31 weeks of gestation and 60 years of
      postnatal life. Using immunocytochemistry with antibodies to neurofilament, we
      have found significant changes in the density of dural innervation with age
      RESULTS: The density of innervation increased between 31 and 40 weeks of
      gestation, peaking at term and decreasing in the subsequent 3 months, remaining
      low until the sixth decade. CONCLUSIONS: Our observations are consistent with
      animal studies but are, to our knowledge, the first to show age-related changes
      in the density of innervation in the human dura. They provide new insights into
      the functions of the human dura during development.

PMID- 22395560
TI  - Exciting developments at SAJRT.

PMID- 22395562
TI  - The dual pathway in action: decoupling parallel routes for CO2 production during
      the oscillatory electro-oxidation of methanol.
AB  - As in the case of most small organic molecules, the electro-oxidation of methanol
      to CO(2) is believed to proceed through a so-called dual pathway mechanism. The
      direct pathway proceeds via reactive intermediates such as formaldehyde or formic
      acid, whereas the indirect pathway occurs in parallel, and proceeds via the
      formation of adsorbed carbon monoxide (CO(ad)). Despite the extensive literature
      on the electro-oxidation of methanol, no study to date distinguished the
      production of CO(2) from direct and indirect pathways. Working under, far-from
      equilibrium, oscillatory conditions, we were able to decouple, for the first
      time, the direct and indirect pathways that lead to CO(2) during the oscillatory
      electro-oxidation of methanol on platinum. The CO(2) production was followed by
      differential electrochemical mass spectrometry and the individual contributions
      of parallel pathways were identified by a combination of experiments and
      numerical simulations. We believe that our report opens some perspectives,
      particularly as a methodology to be used to identify the role played by surface
      modifiers in the relative weight of both pathways-a key issue to the effective
      development of catalysts for low temperature fuel cells.

PMID- 22395563
TI  - Maternal mumps antibodies in a cohort of children up to the age of 1 year.
AB  - The duration of the presence of maternal mumps antibodies in a prospective cohort
      study is presented. Immunoglobulin G against mumps was portioned with a
      commercial ELISA test (Euroimmun(r) anti-mumps Virus AT ELISA, Germany) on
      samples from 213 mother-child pairs at seven time points between pregnancy and 12
      months of age. Non-linear mixed models were used to model maternal antibody decay
      in infants. The model-based median time to loss of antibodies was 3.6 months. The
      median child-specific time to loss of antibodies in children of naturally immune
      women (3.8 months) and children of vaccinated women (2.4 months) differed
      significantly (p = 0.025). The log antibody level of the mother and the log birth
      weight were correlated with the duration of maternal antibodies in infants (p <
      0.0001). CONCLUSION: Children of vaccinated women loose maternal mumps antibodies
      significantly earlier in life compared to children of naturally infected women.
      If early administration (<12 months) of the combined measles, mumps, and rubella
      vaccine is needed, maternal mumps antibodies are not expected to interfere with
      infant humoral vaccine responses.

PMID- 22395564
TI  - Procedural pain in children: education and management. The approach of an Italian
      pediatric pain center.
AB  - Pain management should be warranted for all children in every situation. Italian
      legislation proposes a model for pain assistance based on specialized tertiary
      centers which provide direct clinical management for complex cases and assure
      continuous cooperation with hospitals and family pediatricians for managing
      painful conditions every day. The Procedural Pain Service of the University of
      Padua Department of Pediatrics applies such model for procedural pain management.
      We describe activities of Service since January 1, 2006 on two levels: education
      and training for territorial services and sedation-analgesia when required for
      invasive and painful procedures. Since 2006 to date, the Service team produced an
      internal protocol for procedural sedation, developed two master courses, and
      organized a training program for procedural pain management in the territorial
      context. Procedural sedation-analgesia service provided overall 10,832 sedations
      to perform 14,264 procedures for 3,815 patients, median age of 6 years old. The
      most frequently performed procedures were lumbar puncture and bone marrow
      aspiration, followed by gastroscopy and bronchoscopy. Most frequently
      administered drug combinations were local analgesia + intravenous midazolam alone
      or midazolam and propofol or midazolam and propofol and ketamine; most frequently
      used non-pharmacological methods were distraction using cartoons and bubbles.
      Minor adverse events were recorded in 281 cases (2.5%), the most common being
      desaturation (2.1%). In conclusion, our model functions on two integrated levels,
      and it can be considered generally applicable as a solution for pain management.

PMID- 22395565
TI  - Impact of fluctuating patterns of bronchiolitis epidemics in infants.

PMID- 22395567
TI  - The controversy regarding the need for hormonal treatment in boys with unilateral
      cryptorchidism goes on: a review of the literature.
AB  - Hormonal treatment for unilateral undescended testes continues to be recommended
      in some countries. We reviewed the literature in favor and against this
      recommendation. Since the paternity rate of men with a history of unilateral
      undescended testes only treated with surgery is normal, the effectiveness of
      hormonal treatment to produce testicular descent is low, the cost is
      considerable, and there are potential adverse effects, hormonal treatment for
      boys with unilateral undescended testes should no longer be recommended.

PMID- 22395568
TI  - Accumulation of magnetic iron oxide nanoparticles coated with variably sized
      polyethylene glycol in murine tumors.
AB  - Iron oxide nanoparticles have found widespread applications in different areas
      including cell separation, drug delivery and as contrast agents. Due to water
      insolubility and stability issues, nanoparticles utilized for biological
      applications require coatings such as the commonly employed polyethylene glycol
      (PEG). Despite its frequent use, the influence of PEG coatings on the
      physicochemical and biological properties of iron nanoparticles has hitherto not
      been studied in detail. To address this, we studied the effect of 333-20,000 Da
      PEG coatings that resulted in larger hydrodynamic size, lower surface charge,
      longer circulation half-life, and lower uptake in macrophage cells when the
      particles were coated with high molecular weight (M(w)) PEG molecules. By use of
      magnetic resonance imaging, we show coating-dependent in vivo uptake in murine
      tumors with an optimal coating M(w) of 10,000 Da.

PMID- 22395569
TI  - Stem cell therapy in chronic liver disease.
AB  - PURPOSE OF REVIEW: To provide an overview of the current status of liver
      regeneration therapies for liver cirrhosis and future prospects. RECENT FINDINGS:
      Various clinical studies for liver disease have been reported, including hepatic
      administration of autologous CD34-positive cells induced by granulocyte colony
      stimulating factor, portal vein administration of CD133-positive mononuclear
      cells, and administration of autologous bone marrow-derived mesenchymal stem
      cells. Effectiveness of these approaches has been shown in some patients. We have
      also reported improved liver fibrosis and function with infusion of autologous
      bone marrow cells in a basic study with mice, and on the basis of those results
      started autologous bone marrow cell infusion (ABMi) therapy for liver cirrhosis.
      The efficacy and safety of ABMi therapy has also been reported by other
      institutions. SUMMARY: Results of recent clinical studies strongly suggest that
      liver function-improving effects can be achieved using infusion of bone marrow
      (stem) cells for cirrhosis. New treatment methods using less-invasive bone marrow
      derived cultured cells need to be developed.

PMID- 22395570
TI  - Metals and the liver.
AB  - PURPOSE OF REVIEW: Hereditary liver diseases resulting in copper and iron
      overload may cause significant morbidity and mortality if not diagnosed and
      treated early. The goal of this review is to highlight the key publications on
      genetics, diagnosis and management of hemochromatosis and Wilson disease over the
      past 18 months. RECENT FINDINGS: Several recent advancements have been made in
      the genetic diagnosis of hemochromatosis and Wilson disease. Uncommon HFE
      mutations resulting in phenotypic hemochromatosis among C282Y heterozygotes have
      been identified from HFE gene sequencing. A serum ferritin less than 1000 MUg/l
      in C282Y homozygotes was found to be associated with milder symptoms of
      hemochromatosis. Deferasirox was shown to reduce iron overload in patients with
      hemochromatosis and may be an option for patients who cannot tolerate phlebotomy.
      There was found to be evidence of genotype and phenotype correlation in Wilson
      disease, which can be diagnosed by genetic sequencing. A modified diagnostic
      guideline has been developed for children with Wilson disease with mild liver
      disease that increases the sensitivity and specificity of diagnosis. Also
      treatment with copper chelating agents has less hepatic treatment failures when
      compared with zinc monotherapy. SUMMARY: Advancements in diagnosis of
      hemochromatosis and Wilson disease may lead to earlier diagnosis and treatment
      with resulting decrease in morbidity and mortality.

PMID- 22395572
TI  - Immunosensor towards low-cost, rapid diagnosis of tuberculosis.
AB  - A rapid, accurate tuberculosis diagnostic tool that is compatible with the needs
      of tuberculosis-endemic settings is a long-sought goal. An immunofluorescence
      microtip sensor is described that detects Mycobacterium tuberculosis complex
      cells in sputum in 25 minutes. Concentration mechanisms based on flow circulation
      and electric field are combined at different scales to concentrate target
      bacteria in 1 mL samples onto the surfaces of microscale tips. Specificity is
      conferred by genus-specific antibodies on the microtip surface.
      Immunofluorescence is then used to detect the captured cells on the microtip. The
      detection limit in sputum is 200 CFU mL(-1) with a success rate of 96%, which is
      comparable to PCR.

PMID- 22395571
TI  - Genetic profiling of intrahepatic cholangiocarcinoma.
AB  - PURPOSE OF REVIEW: Intrahepatic cholangiocarcinoma (ICC) is a treatment
      refractory disease with a dismal outcome. Limited success in the clinical
      management and a persistent increase in the incidence world-wide have made ICC
      one of the most lethal and fastest growing malignancies. However, recent
      advancements in genome-wide technologies combined with the application of
      integrative multidimensional analytical approaches have begun to provide both
      detailed insight into the underlying biological traits of ICC and identified new
      therapeutic opportunities. RECENT FINDINGS: In comparison with other cancers,
      genomic studies of ICC have been limited. We and others have recently procured
      large cohorts of ICC patients intended for genome-wide analyses. In our study,
      samples from ICC patients were obtained from three cancer centers and subjected
      to integrated genetic and genomic analyses. We provided new insights into both
      pathogenesis and optimal treatment options demonstrating the presence of unique
      subclasses of patients, based partly on KRAS mutations and increased levels of
      receptor tyrosine kinase signaling. The group of patients with the worst
      prognosis was characterized by transcriptional enrichment of genes regulating
      inflammation and proteasome activities, suggesting a combination of tyrosine
      kinase inhibitors and anti-inflammatory drugs as a new therapeutic option for
      these patients. SUMMARY: We have critically examined the progress in genome-wide
      studies of ICC including genetic profiling, transcriptomics, and epigenomics.
      Current limitations in applying these technologies to archival samples and the
      insufficient access to fresh-frozen material are partly the cause of the delayed
      implementation of the omics-based investigations of ICC compared to other
      hepatobiliary diseases. Thus, selected candidate single-gene studies will also be
      discussed.

PMID- 22395573
TI  - Relationship between some clinical situations, autoantibodies, and
      pseudothrombocytopenia.
AB  - The widespread usage of blood count autoanalyzers has led to a major improvement
      in cellular hematology because of quick and accurate results found in most
      instances. However, spurious test results also can be observed like
      pseudothrombocytopenia (PTCP). In our study, we aimed to evaluate the clinical
      and laboratory factors associated with PTCP. Forty-six patients with PTCP and 69
      healthy volunteers were enrolled in the study. Sex distribution was similar
      between the groups. Hospitalization, infection, the use of low-molecular-weight
      heparin and pregnancy increased the incidence of PTCP. Atherosclerosis and some
      drugs such as warfarin and calcium channel blockers were associated with PTCP,
      but the coincidence was not statistically significant. Antinuclear antibody
      positivity was higher in PTCP group (18.8% vs 7.2%; P=0.033) but anticardiolipin
      positivity rates were similar when compared to controls. Pseudothrombocytopenia
      was frequently misdiagnosed, which led to inappropiate treatments. Therefore,
      this situation should be kept in mind.

PMID- 22395574
TI  - Structural and pharmacological profile of generic enoxaparins used in Brazil.
AB  - Generic active pharmaceutical ingredients (APIs) have been commonly used in
      Brazil, since 1999, but most of them are synthetic and small molecules. Recently,
      a large number of generic enoxaparins were introduced into the market raising
      concerns related to product-to-product interchangeability, efficiency, and drug
      counterfeiting. These drugs are produced from biological sources and their
      production involves complex procedures and purification processes. The present
      article evaluates several generic enoxaparins, structurally and
      pharmacologically, and compares them with the branded products. Structural
      analysis showed that the generic products are, indeed, quite similar to the
      branded products, however, this similarity cannot be extended to their
      pharmacological activities. The results showed that generic products must go
      through extensive structural, pharmacological, and clinical evaluation in order
      to assess their quality, efficacy and, ultimately, avoid drug counterfeiting
      before clinical use. Variation was also observed between the branded products,
      showing that such drugs must be at constant surveillance.

PMID- 22395575
TI  - Feasibility of using thrombin generation assay (TGA) for monitoring bypassing
      agent therapy in patients with hemophilia having inhibitors.
AB  - BACKGROUND: Monitoring bypassing agent therapy and observing concordance with
      clinical hemostasis is crucial in vital hemorrhages and major surgeries in
      patients with hemophilia having inhibitor. OBJECTIVE: We aimed to investigate the
      value of the thrombin generation assay (TGA) and thromboelastography (TEG) for
      monitoring hemostasis in patients with hemophilia having inhibitor, during
      supplementation therapy with bypassing agents. PATIENTS AND METHODS: The study
      group consisted of 7 patients with hemophilia having factor VIII inhibitor. All
      patients were male. The median age of the participants was 10 years. Age range
      was 6 to 32 years. The median inhibitor level was 10 Bethesda units (BU), with a
      range of 5 to 32 BU. A total of 17 bleeding episodes were evaluated. Both TEG and
      TGA tests were assessed in addition to clinical responses. Assessments were made
      prior to bypass agent therapy such as recombinant factor VIIa (rFVIIa) or
      activated prothrombin complex concentrate (aPCC) for bleeding episodes, during
      the first hour and 24 hours after either intervention in patients. RESULTS: No
      relation between clinical response and TGA or TEG parameters was found in
      patients. There was no difference between clinical responses after rFVIIa and
      aPCC treatments. However, after aPCC treatment, endogenous thrombin potential and
      peak thrombin levels and also TEG R, K, and alpha angle degrees were
      significantly higher. CONCLUSIONS: In conclusion, we found that the clinical
      effectiveness of bypass therapy in hemophilia cannot be assessed by TGA and TEG.

PMID- 22395577
TI  - One pot synthesis of heterometallic 3d-3d azido architectures: assembling
      strategy and magnetic properties.
AB  - The Cu(II) ions usually have different coordinated geometry to other 3d ions,
      especially Ni(II) and Co(II) ions, in azido-carboxylate mixed ligand systems.
      That provides a potential way to synthesize rare heterometallic 3d-3d azido
      complexes with peculiar magnetic properties. Assembling Cu(II), M(II) (M = Ni and
      Co), azido and nicotinic acid in hydrothermal condition, two novel isomorphic 3D
      heterometallic 3d-3d azido complexes, [CuM(N(3))(2)(nicotinate)(2)](infinity) (M
      = Ni(II) for 1 and Co(II) for 2) were obtained. The structure of the complexes
      can be described as EO azido and syn,syn carboxylate mixed bridged spin sequence
      chains (-1/2-J(1)-1-J(2)-1/2- for 1 and -1/2-J(1)-3/2-J(2)-1/2- for 2) linked by
      the pyridyl groups. Dominant ferromagnetic interactions were observed between the
      Cu(II) and M(II) ions in the chains despite the largest M-N-M angle of about 129
      degrees  in the 3d metal azido-carboxylate mixed coordinated systems and weak
      antiferromagnetic interactions between the chains. At low temperature, a spin
      flop phase transition was present in the Co(II) involved complex 2.

PMID- 22395576
TI  - OsMYB2P-1, an R2R3 MYB transcription factor, is involved in the regulation of
      phosphate-starvation responses and root architecture in rice.
AB  - An R2R3 MYB transcription factor, OsMYB2P-1, was identified from microarray data
      by monitoring the expression profile of rice (Oryza sativa ssp. japonica)
      seedlings exposed to phosphate (Pi)-deficient medium. Expression of OsMYB2P-1 was
      induced by Pi starvation. OsMYB2P-1 was localized in the nuclei and exhibited
      transcriptional activation activity. Overexpression of OsMYB2P-1 in Arabidopsis
      (Arabidopsis thaliana) and rice enhanced tolerance to Pi starvation, while
      suppression of OsMYB2P-1 by RNA interference in rice rendered the transgenic rice
      more sensitive to Pi deficiency. Furthermore, primary roots of OsMYB2P-1
      overexpressing plants were shorter than those in wild-type plants under Pi
      sufficient conditions, while primary roots and adventitious roots of OsMYB2P-1
      overexpressing plants were longer than those of wild-type plants under Pi
      deficient conditions. These results suggest that OsMYB2P-1 may also be associated
      with the regulation of root system architecture. Overexpression of OsMYB2P-1 led
      to greater expression of Pi-responsive genes such as Oryza sativa UDP
      sulfoquinovose synthase, OsIPS1, OsPAP10, OsmiR399a, and OsmiR399j. In contrast,
      overexpression of OsMYB2P-1 suppressed the expression of OsPHO2 under both Pi
      sufficient and Pi-deficient conditions. Moreover, expression of OsPT2, which
      encodes a low-affinity Pi transporter, was up-regulated in OsMYB2P-1
      overexpressing plants under Pi-sufficient conditions, whereas expression of the
      high-affinity Pi transporters OsPT6, OsPT8, and OsPT10 was up-regulated by
      overexpression of OsMYB2P-1 under Pi-deficient conditions, suggesting that
      OsMYB2P-1 may act as a Pi-dependent regulator in controlling the expression of Pi
      transporters. These findings demonstrate that OsMYB2P-1 is a novel R2R3 MYB
      transcriptional factor associated with Pi starvation signaling in rice.

PMID- 22395580
TI  - An update on the long-term safety experience of ustekinumab: results from the
      psoriasis clinical development program with up to four years of follow-up.
AB  - BACKGROUND: The efficacy and safety profile of ustekinumab with up to three years
      of exposure suggested a favorable benefit-risk profile in patients with moderate
      to severe psoriasis. OBJECTIVE: To evaluate the safety of ustekinumab in patients
      with moderate to severe psoriasis treated for up to four years. METHODS: Safety
      data were pooled across four Phase II/III randomized controlled trials. Rates
      over time and cumulative rates of adverse events (AEs), AEs leading to treatment
      discontinuation, serious adverse events (SAEs), serious infections, malignancies,
      and major adverse cardiovascular events (MACE) (i.e., cardiovascular death,
      myocardial infarction [MI], or stroke as adjudicated by an independent panel of
      academic cardiologists) were evaluated. Observed rates of AEs of interest were
      compared with those expected in the general (malignancies, MI, and stroke) and
      psoriasis (serious infections, MI, and stroke) populations. RESULTS: Overall,
      3,117 patients were followed for up to four years (6,791 patient-years). Rates of
      AEs, AEs leading to treatment discontinuation, and SAEs remained stable over
      time, whereas cumulative rates were generally comparable between patients who
      received 45 mg and 90 mg of ustekinumab. The rates of AEs of interest also
      remained stable over time, and cumulative rates per 100 patient-years were 0.80
      and 1.32 (serious infections), 0.70 and 0.53 (nonmelanoma skin cancer), 0.63 and
      0.61 (other malignancies), and 0.56 and 0.46 (MACE) in patients treated with 45
      mg and 90 mg, respectively. Rates of AEs of interest were consistent with those
      in the general and psoriasis populations. CONCLUSION: The safety profile of long
      term ustekinumab treatment with up to four years of continuous use remains
      consistent with previous reports, with no evidence of cumulative toxicity.

PMID- 22395581
TI  - Optimizing topical combination therapy for the treatment of acne vulgaris.
AB  - Given the multifactorial and complex contributors to acne development,
      combination therapy is standard of care. By addressing multiple pathogenic
      factors, combination therapy provides a quicker and more efficacious treatment
      outcome than monotherapy. Topical retinoids normalize follicular keratinocyte
      differentiation and are anti-inflammatory. Their use is limited by the potential
      for cutaneous irritation. Antimicrobials reduce Propionibacterium acnes
      colonization on the skin and reduce the bacteria's proinflammatory effects.
      Topical antibiotics and benzoyl peroxide (BPO) are commonly employed in fixed
      dose combination products or two separate medications. BPO has the added benefit
      of being comedolytic and can minimize the risk for bacterial antibiotic
      resistance. Like topical retinoids, BPO may cause skin irritation, burning,
      erythema, and peeling. Managing cutaneous side effects when using multiple
      products that cause irritation can be a challenge. Careful product selection,
      dose titration, and patient-directed regimens can help to optimize outcomes. This
      review presents the latest data on two topical acne products that have
      demonstrated excellent efficacy and tolerability profiles. In addition, their in
      vitro profiles suggest the potential for combination use, affording greater
      dosing flexibility.

PMID- 22395583
TI  - Vitamin D supplementation in the treatment of atopic dermatitis: a clinical trial
      study.
AB  - BACKGROUND: The role of vitamin D in Atopic Dermatitis (AD) is ambiguous and
      clinical trials are needed to assess the role of vitamin D in the treatment of
      AD. The aim of this clinical trial study to evaluate the effect of vitamin D
      supplementation on patients with AD. MATERIAL AND METHODS: sixty AD patients were
      included in a randomized, double-blind, placebo-controlled trial study. They were
      randomly divided into two groups and treated for 60 days: group vitamin D (n=30),
      and placebo group (n=30). The two groups were as follows: Group D, 1600 IU
      cholecalciferol (vitamin D) and second group placebo. The severity of AD was
      evaluated based on SCORAD (Scoring Atopic Dermatitis) and TIS (Three Item
      Severity score) value by the same trained physician before and after the trial.
      RESULTS: According to SCORAD and TIS value index in the vitamin D group showed
      significant improvement in patients with mild, moderate and severe AD (P<0.05)
      and in patients who the intake placebo, this improvement didn't showed (P>0.05).
      CONCLUSION: Results mention that supplementation with oral vitamin D dramatically
      improved disease severity in AD patients.

PMID- 22395582
TI  - Efficacy and safety of clindamycin-tretinoin gel versus clindamycin or tretinoin
      alone in acne vulgaris: a randomized, double-blind, vehicle-controlled study.
AB  - BACKGROUND: Topical combination therapy containing a retinoid and an
      antimicrobial is an effective treatment for acne vulgaris. OBJECTIVE: To evaluate
      the efficacy and safety of a new topical formulation containing clindamycin
      phosphate 1.2% and tretinoin 0.025% solubilized in an aqueous-based gel (CT gel).
      METHODS: 1,649 participants were randomized 2:2:2:1 to 12 weeks of double-blind
      treatment with CT gel, clindamycin, tretinoin, or vehicle gel administered once
      daily. RESULTS: Significantly more participants achieved 2-grade or greater
      improvement on the Investigator's Static Global Assessment score with CT gel
      versus clindamycin, tretinoin, or vehicle gel. CT gel produced a significantly
      greater reduction in absolute number of total lesions versus all other treatment
      groups, in total and noninflammatory lesions versus clindamycin, and in total and
      inflammatory lesions versus tretinoin. Local tolerability was similar to that of
      tretinoin alone; signs and symptoms of irritation were most notable at week 2.
      There were no more adverse events with CT gel than with tretinoin gel.
      CONCLUSION: CT gel is more effective than clindamycin or tretinoin monotherapy,
      with a safety and tolerability profile similar to that of tretinoin.

PMID- 22395584
TI  - A randomized, double-blind, placebo-controlled, pilot study to assess the
      efficacy and safety of clindamycin 1.2% and tretinoin 0.025% combination gel for
      the treatment of acne rosacea over 12 weeks.
AB  - BACKGROUND: Papulopustular acne rosacea is a chronic inflammatory condition which
      can be difficult to treat. Many patients are unwilling to use systemic
      medications, and single topical agents alone may not address all the symptoms of
      rosacea. A combination topical clindamycin phosphate 1.2% and tretinoin 0.025%
      gel is efficacious for acne vulgaris, and may be helpful for rosacea, since acne
      vulgaris and rosacea shares many similar clinical and histologic features.
      OBJECTIVE: To assess the preliminary efficacy and safety of a combination gel
      consisting of clindamycin phosphate 1.2% and tretinoin 0.025% on papulopustular
      rosacea after 12 weeks of usage. METHODS: Randomized, double-blind, placebo
      controlled two site study of 79 participants with moderate to severe
      papulopustular acne rosacea using both physician and subjects' validated
      assessment tools. Primary endpoint consisted of statistically significant
      reduction in absolute papule or pustule count after 12 weeks of usage. RESULTS:
      There was no significant difference in papule/pustule count between placebo and
      treated groups after 12 weeks (P=0.10). However, there was nearly significant
      improvement in physicians' assessments of the telangiectasia component of rosacea
      (P=0.06) and erythematotelangiectatic rosacea subtype (P=0.05) in treated versus
      placebo group after 12 weeks. The only significant adverse event different was
      facial scaling, which was significantly increased in treated group (P=0.01), but
      this did not result in discontinuation of study drug. CONCLUSIONS: A combination
      gel of clindamycin phosphate 1.2% and tretinoin 0.025% may improve the
      telangiectatic component of rosacea and appears to better treat the
      erythemotelangiectatic subtype of rosacea rather than papulopustular subtype. Our
      preliminary study suggests that future studies with much larger sample size might
      confirm our findings.

PMID- 22395585
TI  - A phase 2, open-label, investigator-initiated study to evaluate the safety and
      efficacy of apremilast in subjects with recalcitrant allergic contact or atopic
      dermatitis.
AB  - OBJECTIVE: Evaluate the efficacy and safety of apremilast, a novel
      phosphodiesterase 4 (PDE4) inhibitor, in subjects with recalcitrant moderate to
      severe atopic dermatitis (AD) or allergic contact dermatitis (ACD). RESEARCH
      DESIGN AND METHODS: This was a proof-of-concept, phase 2, open-label, single
      institution trial that evaluated the efficacy and safety of apremilast, 20 mg
      twice daily, for twelve weeks, in ten subjects with either AD and/or ACD. The
      primary endpoint was a ?2 point improvement in Investigator Global Assessment
      (IGA) score after 12 weeks of treatment. Secondary endpoints included a 75%
      reduction in the Eczema Assessment Severity Index (EASI-75), EASI-50, and the
      maximum EASI response. RESULTS: The primary endpoint of improvement in IGA by two
      or more points was met by 20% of subjects. Ten percent of subjects achieved EASI
      75 and another 10% reached EASI-50. All subjects tolerated apremilast well with
      no serious adverse events or withdrawal due to side effects. Common adverse
      events associated with apremilast included headache, nausea, and soft stool.
      LIMITATIONS: This study was limited by its small sample size and lack of a
      comparison group to serve as a control. CONCLUSIONS: Apremilast was well
      tolerated in all subjects. Apremilast was minimally effective in AD and ACD and
      results were inferior to previous trials of apremilast in psoriasis.

PMID- 22395586
TI  - Combination of essential oil of Melaleuca alternifolia and iodine in the
      treatment of molluscum contagiosum in children.
AB  - Molluscum contagiosum is a common childhood viral skin condition and is
      increasingly found as a sexually transmitted disease in adults. Current treatment
      options are invasive, requiring tissue destruction and attendant discomfort.
      Fifty-three children (mean age 6.3+5.1 years) with the diagnosis of molluscum
      contagiosum were treated with twice daily topical application of either essential
      oil of Melaleuca alternifolia (TTO), a combination of TTO and organically bound
      iodine (TTO-I), or iodine alone. At the end of 30 days, 48 children were
      available for follow up. A greater than 90% reduction in the number of lesions
      was observed in 16 of 19 children treated with TTO-I, while 1 of 16 and 3 of 18
      children met the same criteria for improvement in the iodine and TTO groups
      (P<0.01, ANOVA) respectively by intention-to-treat analysis. No child
      discontinued treatment due to adverse events. The combination of essential oil of
      M. alternifolia with organically bound iodine offers a safe therapeutic
      alternative in the treatment of childhood molluscum. Clinical Trial Registry
      ACTRN12610000984099.

PMID- 22395587
TI  - Treatment of scabies using 8% and 10% topical sulfur ointment in different
      regimens of application.
AB  - BACKGROUND: Many therapeutic modalities for scabies were available, topical
      sulfur ointment is a cost-effective and safe therapeutic agent. It is often
      applied for the whole body for three successive days. OBJECTIVE: To evaluate
      their therapeutic regimen of 8% and 10% topical precipitated sulfur in petrolatum
      ointment for single day, three successive nights or three successive days in
      management of scabies. PATIENTS AND METHODS: This single-blinded, comparative
      study was conducted in the Department of Dermatology-Baghdad Teaching Hospital
      from April 2008 through October 2009. A total of 97 patients with scabies were
      enrolled in this study. The diagnosis was established on clinical basis. The
      patients treated with 8% and 10% topical sulfur in petrolatum ointment were
      divided randomly into three groups: Group A: 33 patients treated for single day
      (24 hours); Group B: 32 patients treated for three successive nights (from 6 p.m.
      to 8 p.m. to 6 a.m. to 8 a.m. and bathing every day); and Group C: 32 patients
      treated for three successive days (bathing every 24 hours). The patients were
      seen regularly every two weeks for the duration of four weeks. RESULTS: Study
      included 58 (59.8%) males and 39 (40.2%) females, with a male to female ratio
      1.4:1. The age range of males at presentation from 3 to 64 (26.74+/-15.98) years,
      while the females age ranged at presentation from 3 to 60 (24.05+/-14.53) years
      of age. At the end of the study, the response to treatment was: Group A, response
      in 14 (42.4%) patients and no response in 19 (57.6%); Group B, response in 29
      (90.6%) patients and no response in 3 (9.4%); and Group C, response in 31 (96.9%)
      patients and no response in 1 (3.1%). There is significant statistical difference
      among the response of 3 groups with (P=0.00000011), but no statistically
      significant difference between the response of Group C and Group B, (P=0.6055).
      Mild burning sensation and irritating (sulfur) dermatitis were the only side
      effects of 8% and 10% sulfur. Pruritic rash occurred in Group C mainly, in 11
      (34.4%) patients, 8 (25%) in Group B and 4 (12.1%) in Group A, with no
      significance (P=0.1058). Recurrence or relapse occurred in Group A mainly, with 4
      (12.1%) patients, and in Group B, 1 patient, (3.1%), with no recurrence in group
      C, with significance (P=0.0060). CONCLUSION: Three successive days and three
      successive nights of 8% and 10% sulfur ointment were effective regimens with no
      statistical difference in favor of three successive days, while single-day
      application was much less effective but with fewer side effects.

PMID- 22395588
TI  - Comparative trial of 5% dexpanthenol in water-in-oil formulation with 1%
      hydrocortisone ointment in the treatment of childhood atopic dermatitis: a pilot
      study.
AB  - BACKGROUND: Atopic dermatitis (AD) is a common chronic relapsing disease
      particularly affecting children. The emollient used for protection of skin
      barrier function is the standard treatment for patients with AD. Currently, there
      is a growing interest in the use of nonsteroidal anti-inflammatory agents such as
      dexpanthenol (vitamin B5) as an alternative treatment. OBJECTIVE: To compare the
      effectiveness of 5% dexpanthenol (DT) ointment with 1% hydrocortisone (HC)
      ointment in childhood AD therapy. METHOD: Patients were treated topically with 5%
      DT ointment on the right side of the body and 1% HC ointment on the other side
      twice daily for 4 weeks. The clinical responses were evaluated by SCORAD (Scoring
      Atopic Dermatitis index) with statistical analysis using paired t-test. RESULT:
      Of the 30 children enrolled, 26 completed the protocol; mean age was 7.19 years.
      The average baseline SCORAD score of the DT-treated side and the HC-treated side
      was 30.95 and 30.54, respectively. There was no statistically significant
      difference in SCORAD score reduction between the 2 agents. The edematous score of
      the HC-treated side exhibited faster resolution than that of the DT-treated side,
      with a statistically significant difference at week 1 and without a statistically
      significant difference at weeks 2 to 4. The lichenification response rate of HC
      treatment was more rapid than that of DT treatment; however, there was no
      statistical group difference. No adverse events were observed with either agent.
      CONCLUSION: The effectiveness of 5% DT ointment is equal to that of 1% HC
      ointment. DT ointment may be used as alternative treatment in mild to moderate
      childhood AD therapy.

PMID- 22395589
TI  - Nasal ala reconstruction with a crus helix composite graft: a stepladder
      approach.
AB  - BACKGROUND: Defects of the nasal ala present a complex reconstructive challenge.
      Composite grafts comprise all layers required to successfully reconstruct these
      full thickness deformities making them the ideal reconstructive method, yet they
      are usually avoided because of unjustified disreputable failure rates. OBJECTIVE:
      The authors introduce a stepladder approach for alar reconstruction with a crus
      of helix composite graft according to the severity and complexity of the defect.
      METHODS: Data from 25 patients who underwent correction of full thickness alar
      defects with composite grafts was collected and reviewed. RESULTS: There were no
      complete graft failures in any of the cases. Ten patients (40%) had partial graft
      necrosis ranging from 5 to 50% (average 18%); two of them (20%) were heavy
      smokers. CONCLUSIONS: Composite grafts should be considered for reconstruction of
      full thickness nasal ala defects, given the correct surgical technique is
      implemented.

PMID- 22395590
TI  - Hypopigmented cutaneous sarcoidosis responsive to minocycline.
AB  - Hypopigmented patches and plaques are a rare presentation of cutaneous
      sarcoidosis. We describe a case of generalized hypopigmented cutaneous
      sarcoidosis that showed good response to minocycline therapy.

PMID- 22395592
TI  - A lupus-like reaction to subcutaneous interferon-alpha at injection sites.
AB  - Interferon-alpha has been associated with a wide range of adverse events (AEs). A
      lupus-like reaction at the injection site of subcutaneous (SC) interferon-alpha
      is exceptionally rare. A 60-year-old woman with recurrent metastatic melanoma
      repeatedly developed cutaneous lupus-like reactions at the SC interferon-alpha-2b
      injection sites on her thighs. Known features of lupus-like reactions at SC
      interferon-alpha injection sites are reviewed, and cutaneous injection site
      reactions to SC interferon-alpha are summarized.

PMID- 22395594
TI  - A case of elephantiasis nostras verrucosa treated by acitretin.
AB  - Elephantiasis nostras verrucosa is a rare disorder characterized by dermal
      fibrosis, hyperkeratotic, verrucous, and papillomatous lesions that result from
      both chronic filarial and nonfilarial lymphedema. Various treatment options have
      been reported for this disease. We present a 64-year-old man with erythrodermic
      psoriasis and elephantiasis nostras verrucosa in whom the lesions were resolved
      almost completely after acitretin treatment.

PMID- 22395595
TI  - Adrenergic urticaria and rheumatoid arthritis in a patient with melanoma: an
      intricate medical management.
AB  - A 45-year-old woman with marital and working troubles, a personal history
      positive for malignant melanoma, and a family history of vitiligo presented with
      adrenergic urticaria (AU), which at first responded to propranolol, but later
      became unresponsive to both ?-blockers and antihistamines. Meanwhile, rheumatoid
      arthritis became apparent. Treatment with corticosteroids and methotrexate led to
      remission of neither the rheumatologic nor the dermatologic condition. Attempts
      to taper the immunosuppressive treatment were invariably followed by recurrence
      of adrenergic urticaria, which still proved unresponsive to propranolol, as did
      the rheumatoid arthritis. The courses of the diseases strictly paralleled each
      other. Rheumatoid arthritis could have triggered adrenergic urticaria by simply
      adding a supplemental stress, but also by systemically activating mast cells,
      which are known to be involved in the pathogenesis of chronic inflammatory
      diseases. A brief discussion of either the dermatological manifestations of, or
      treatments for rheumatoid arthritis is provided, in order to illustrate the kind
      of clinical difficulties that such atypical patients pose to physicians.
      Adrenergic urticaria is an uncommon yet probably under-diagnosed form of
      urticaria, which is considered a form of neurogenic acute reaction mainly
      triggered by acute stress. The author presents a case of AU, however, that is
      only partially explained by a stress setting, though it is strongly associated
      with the course of an autoimmune disease.

PMID- 22395596
TI  - Long-term etanercept use for severe generalized psoriasis in an HIV-infected
      individual: a case study.
AB  - The treatment options for psoriasis in HIV-infected individuals are limited due
      to the immunosuppressive nature of the therapeutic modalities and the patient's
      immunocompromised state. Etanercept has been shown to be safe and effective in
      the non-HIV psoriasis population with nearly 20 years of experience. However,
      there is limited data on the safety of etanercept use in the HIV patient
      population. The authors report a case of an HIV-infected patient with psoriasis
      who has remained mostly clear on continuous, uninterrupted etanercept use for
      over six years.

PMID- 22395597
TI  - Leukemia cutis.

PMID- 22395598
TI  - MelaFind is approved by the FDA: where does it fit in dermatology?

PMID- 22395601
TI  - A Bayesian two-level model for fluctuation assay.
AB  - The fluctuation experiment is an essential tool for measuring microbial mutation
      rates in the laboratory. When inferring the mutation rate from an experiment, one
      assumes that the number of mutants in each test tube follows a common
      distribution. This assumption conceptually restricts the scope of applicability
      of fluctuation assay. We relax this assumption by proposing a Bayesian two-level
      model, under which an experiment-wide average mutation rate can be defined. The
      new model suggests a gamma mixture of the Luria-Delbruck distribution, which
      coincides with a recently discovered discrete distribution. While the mixture
      model is of considerable independent interest in fluctuation assay, it also
      offers a practical Markov chain Monte Carlo method for estimating mutation rates.
      We illustrate the Bayesian approach with a detailed analysis of an actual
      fluctuation experiment.

PMID- 22395602
TI  - Measuring left ventricular pressure in late embryonic and neonatal mice.
AB  - Blood pressure increases significantly during embryonic and postnatal development
      in vertebrate animals. In the mouse, blood flow is first detectable around
      embryonic day (E) 8.5(1). Systolic left ventricular (LV) pressure is 2 mmHg at
      E9.5 and 11 mmHg at E14.5(2). At these mid-embryonic stages, the LV is clearly
      visible through the chest wall for invasive pressure measurements because the
      ribs and skin are not fully developed. Between E14.5 and birth (approximately
      E21) imaging methods must be used to view the LV. After birth, mean arterial
      pressure increases from 30 - 70 mmHg from postnatal day (P) 2 - 35(3). Beyond
      P20, arterial pressure can be measured with solid-state catheters (i.e. Millar or
      Scisense). Before P20, these catheters are too big for developing mouse arteries
      and arterial pressure must be measured with custom pulled plastic catheters
      attached to fluid-filled pressure transducers(3) or glass micropipettes attached
      to servo null pressure transducers(4).    Our recent work has shown that the
      greatest increase in blood pressure occurs during the late embryonic to early
      postnatal period in mice(5-7). This large increase in blood pressure may
      influence smooth muscle cell (SMC) phenotype in developing arteries and trigger
      important mechanotransduction events. In human disease, where the mechanical
      properties of developing arteries are compromised by defects in extracellular
      matrix proteins (i.e. Marfan's Syndrome(8) and Supravalvular Aortic Stenosis(9))
      the rapid changes in blood pressure during this period may contribute to disease
      phenotype and severity through alterations in mechanotransduction signals.
      Therefore, it is important to be able to measure blood pressure changes during
      late embryonic and neonatal periods in mouse models of human disease.    We
      describe a method for measuring LV pressure in late embryonic (E18) and early
      postnatal (P1 - 20) mice. A needle attached to a fluid-filled pressure transducer
      is inserted into the LV under ultrasound guidance. Care is taken to maintain
      normal cardiac function during the experimental protocol, especially for the
      embryonic mice. Representative data are presented and limitations of the protocol
      are discussed.

PMID- 22395603
TI  - The tRNA methyltransferase NSun2 stabilizes p16INK4 mRNA by methylating the 3'
      untranslated region of p16.
AB  - The impact of methylation of the 3'-untranslated region (UTR) of a messenger RNA
      (mRNA) remains largely unknown. Here we show that NSun2, a transfer RNA
      methyltransferase, inhibits the turnover of p16(INK4) mRNA. Knockdown of NSun2
      reduces p16 expression by shortening the half-life of the p16 mRNA, while
      overexpression of NSun2 stabilizes the p16 mRNA. In vitro methylation assays show
      that NSun2 methylates the p16 3'UTR at A988. Knockdown of NSun2 reduces the
      stability of the EGFP-p16 chimeric reporter transcripts bearing wild-type p16
      3'UTR, but not p16 3'UTR with a mutant methylation site. Methylation by NSun2
      prevents the association of p16 3'UTR with HuR, AUF1 and Ago2/RISC, and prevents
      the recruitment of EGFP-p16 3'UTR chimeric transcripts to processing bodies. In
      response to oxidative stress, NSun2 is essential for elevating p16 expression
      levels. We conclude that NSun2-mediated methylation of the p16 3'UTR is a novel
      mechanism to stabilize p16 mRNA.

PMID- 22395604
TI  - Acquisition of aluminium tolerance by modification of a single gene in barley.
AB  - Originating from the Fertile Crescent in the Middle East, barley has now been
      cultivated widely on different soil types including acid soils, where aluminium
      toxicity is a major limiting factor. Here we show that the adaptation of barley
      to acid soils is achieved by the modification of a single gene (HvAACT1) encoding
      a citrate transporter. We find that the primary function of this protein is to
      release citrate from the root pericycle cells to the xylem to facilitate the
      translocation of iron from roots to shoots. However, a 1-kb insertion in the
      upstream of the HvAACT1 coding region occurring only in the Al-tolerant
      accessions, enhances its expression and alters the location of expression to the
      root tips. The altered HvAACT1 has an important role in detoxifying aluminium by
      secreting citrate to the rhizosphere. Thus, the insertion of a 1-kb sequence in
      the HvAACT1 upstream enables barley to adapt to acidic soils.

PMID- 22395605
TI  - Structure of the pentameric ligand-gated ion channel ELIC cocrystallized with its
      competitive antagonist acetylcholine.
AB  - ELIC, the pentameric ligand-gated ion channel from Erwinia chrysanthemi, is a
      prototype for Cys-loop receptors. Here we show that acetylcholine is a
      competitive antagonist for ELIC. We determine the acetylcholine-ELIC cocrystal
      structure to a 2.9-A resolution and find that acetylcholine binding to an
      aromatic cage at the subunit interface induces a significant contraction of loop
      C and other structural rearrangements in the extracellular domain. The side chain
      of the pore-lining residue F247 reorients and the pore size consequently
      enlarges, but the channel remains closed. We attribute the inability of
      acetylcholine to activate ELIC primarily to weak cation-pi and electrostatic
      interactions in the pocket, because an acetylcholine derivative with a simple
      quaternary-to-tertiary ammonium substitution activates the channel. This study
      presents a compelling case for understanding the structural underpinning of the
      functional relationship between agonism and competitive antagonism in the Cys
      loop receptors, providing a new framework for developing novel therapeutic drugs.

PMID- 22395606
TI  - Perpendicular exchange bias in ferrimagnetic spin valves.
AB  - The exchange bias effect refers to the shift of the hysteresis loop of a
      ferromagnet in direct contact to an antiferromagnet. For applications in
      spintronics a robust and tunable exchange bias is required. Here we show
      experimental evidence for a perpendicular exchange bias in a prototypical
      ferrimagnetic spin valve consisting of DyCo(5)/Ta/Fe(76)Gd(24), where the DyCo(5)
      alloy has the role of a hard ferrimagnet and Fe(76)Gd(24) is a soft ferrimagnet.
      Taking advantage of the tunability of the exchange coupling between the
      ferrimagnetic layers by means of thickness variation of an interlayer spacer, we
      demonstrate that perpendicular unidirectional anisotropy can be induced with
      desirable absolute values at room temperature, without making use of a field
      cooling procedure. Moreover, the shift of the hysteresis loop can be reversed
      with relatively low magnetic fields of several hundred Oersteds. This flexibility
      in controlling a robust perpendicular exchange bias at room temperature may be of
      crucial importance for applications.

PMID- 22395607
TI  - Host factors dictate control of viral replication in two HIV-1 controller/chronic
      progressor transmission pairs.
AB  - Viremic controllers and elite controllers/suppressors maintain control over HIV-1
      replication. Some studies have suggested that control is a result of infection
      with a defective viral strain, while others suggested host immune factors have a
      key role. Here we document two HIV-1 transmission pairs: one consisting of a
      patient with progressive disease and an individual who became an elite
      suppressor, and the second consisting of a patient with progressive disease and a
      viremic controller. In contrast to another elite suppressor transmission pair,
      virus isolated from all patients was fully competent. These data suggest that
      some viremic controllers and elite suppressors are infected with HIV-1 isolates
      that replicate vigorously in vitro and are able to cause progressive disease in
      vivo. These data suggest that host factors have a dominant role in the control of
      HIV-1 infection, thus it may be possible to control fully pathogenic HIV-1
      isolates with therapeutic vaccination.

PMID- 22395608
TI  - RUNX1-induced silencing of non-muscle myosin heavy chain IIB contributes to
      megakaryocyte polyploidization.
AB  - Megakaryocytes are unique mammalian cells that undergo polyploidization
      (endomitosis) during differentiation, leading to an increase in cell size and
      protein production that precedes platelet production. Recent evidence
      demonstrates that endomitosis is a consequence of a late failure in cytokinesis
      associated with a contractile ring defect. Here we show that the non-muscle
      myosin IIB heavy chain (MYH10) is expressed in immature megakaryocytes and
      specifically localizes in the contractile ring. MYH10 downmodulation by short
      hairpin RNA increases polyploidization by inhibiting the return of 4N cells to
      2N, but other regulators, such as of the G1/S transition, might regulate further
      polyploidization of the 4N cells. Conversely, re-expression of MYH10 in the
      megakaryocytes prevents polyploidization and the transition of 2N to 4N cells.
      During polyploidization, MYH10 expression is repressed by the major megakaryocyte
      transcription factor RUNX1. Thus, RUNX1-mediated silencing of MYH10 is required
      for the switch from mitosis to endomitosis, linking polyploidization with
      megakaryocyte differentiation.

PMID- 22395609
TI  - gamma-Glutamylcysteine detoxifies reactive oxygen species by acting as
      glutathione peroxidase-1 cofactor.
AB  - Reactive oxygen species regulate redox-signaling processes, but in excess they
      can cause cell damage, hence underlying the aetiology of several neurological
      diseases. Through its ability to down modulate reactive oxygen species,
      glutathione is considered an essential thiol-antioxidant derivative, yet under
      certain circumstances it is dispensable for cell growth and redox control. Here
      we show, by directing the biosynthesis of gamma-glutamylcysteine-the immediate
      glutathione precursor-to mitochondria, that it efficiently detoxifies hydrogen
      peroxide and superoxide anion, regardless of cellular glutathione concentrations.
      Knocking down glutathione peroxidase-1 drastically increases superoxide anion in
      cells synthesizing mitochondrial gamma-glutamylcysteine. In vitro, gamma
      glutamylcysteine is as efficient as glutathione in disposing of hydrogen peroxide
      by glutathione peroxidase-1. In primary neurons, endogenously synthesized gamma
      glutamylcysteine fully prevents apoptotic death in several neurotoxic paradigms
      and, in an in vivo mouse model of neurodegeneration, gamma-glutamylcysteine
      protects against neuronal loss and motor impairment. Thus, gamma-glutamylcysteine
      takes over the antioxidant and neuroprotective functions of glutathione by acting
      as glutathione peroxidase-1 cofactor.

PMID- 22395610
TI  - Dimensional and temporal controls of three-dimensional cell migration by zyxin
      and binding partners.
AB  - Spontaneous molecular oscillations are ubiquitous in biology. But to our
      knowledge, periodic cell migratory patterns have not been observed. Here we
      report the highly regular, periodic migration of cells along rectilinear tracks
      generated inside three-dimensional matrices, with each excursion encompassing
      several cell lengths, a phenotype that does not occur on conventional substrates.
      Short hairpin RNA depletion shows that these one-dimensional oscillations are
      uniquely controlled by zyxin and binding partners alpha-actinin and p130Cas, but
      not vasodilator-stimulated phosphoprotein and cysteine-rich protein 1.
      Oscillations are recapitulated for cells migrating along one-dimensional
      micropatterns, but not on two-dimensional compliant substrates. These results
      indicate that although two-dimensional motility can be well described by speed
      and persistence, three-dimensional motility requires two additional parameters,
      the dimensionality of the cell paths in the matrix and the temporal control of
      cell movements along these paths. These results also suggest that the zyxin/alpha
      actinin/p130Cas module may ensure that motile cells in a three-dimensional matrix
      explore the largest space possible in minimum time.

PMID- 22395611
TI  - The biology and chemistry of high-valent iron-oxo and iron-nitrido complexes.
AB  - Selective functionalization of unactivated C-H bonds and ammonia production are
      extremely important industrial processes. A range of metalloenyzmes achieve these
      challenging tasks in biology by activating dioxygen and dinitrogen using cheap
      and abundant transition metals, such as iron, copper and manganese. High-valent
      iron-oxo and -nitrido complexes act as active intermediates in many of these
      processes. The generation of well-described model compounds can provide vital
      insights into the mechanism of such enzymatic reactions. Advances in the
      chemistry of model high-valent iron-oxo and -nitrido systems can be related to
      our understanding of the biological systems.

PMID- 22395612
TI  - Ultrafast changes in lattice symmetry probed by coherent phonons.
AB  - The electronic and structural properties of a material are strongly determined by
      its symmetry. Changing the symmetry via a photoinduced phase transition offers
      new ways to manipulate material properties on ultrafast timescales. However, to
      identify when and how fast these phase transitions occur, methods that can probe
      the symmetry change in the time domain are required. Here we show that a time
      dependent change in the coherent phonon spectrum can probe a change in symmetry
      of the lattice potential, thus providing an all-optical probe of structural
      transitions. We examine the photoinduced structural phase transition in VO(2) and
      show that, above the phase transition threshold, photoexcitation completely
      changes the lattice potential on an ultrafast timescale. The loss of the
      equilibrium-phase phonon modes occurs promptly, indicating a non-thermal pathway
      for the photoinduced phase transition, where a strong perturbation to the lattice
      potential changes its symmetry before ionic rearrangement has occurred.

PMID- 22395613
TI  - LIS1-dependent retrograde translocation of excitatory synapses in developing
      interneuron dendrites.
AB  - Synaptic remodelling coordinated with dendritic growth is essential for proper
      development of neural connections. After establishment of synaptic contacts,
      synaptic junctions are thought to become stationary and provide fixed anchoring
      points for further dendritic growth. However, the possibility of active
      translocation of synapses along dendritic protrusions, to guide the proper
      arrangement of synaptic distribution, has not yet been fully investigated. Here
      we show that immature dendrites of gamma-aminobutyric acid-positive interneurons
      form long protrusions and that these protrusions serve as conduits for retrograde
      translocation of synaptic contacts to the parental dendrites. This translocation
      process is dependent on microtubules and the activity of LIS1, an essential
      regulator of dynein-mediated motility. Suppression of this retrograde
      translocation results in disorganized synaptic patterns on interneuron dendrites.
      Taken together, these findings suggest the existence of an active microtubule
      dependent mechanism for synaptic translocation that helps in the establishment of
      proper synaptic distribution on dendrites.

PMID- 22395614
TI  - Organic transistors with high thermal stability for medical applications.
AB  - The excellent mechanical flexibility of organic electronic devices is expected to
      open up a range of new application opportunities in electronics, such as flexible
      displays, robotic sensors, and biological and medical electronic applications.
      However, one of the major remaining issues for organic devices is their
      instability, especially their thermal instability, because low melting
      temperatures and large thermal expansion coefficients of organic materials cause
      thermal degradation. Here we demonstrate the fabrication of flexible thin-film
      transistors with excellent thermal stability and their viability for biomedical
      sterilization processes. The organic thin-film transistors comprise a high
      mobility organic semiconductor, dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene,
      and thin gate dielectrics comprising a 2-nm-thick self-assembled monolayer and a
      4-nm-thick aluminium oxide layer. The transistors exhibit a mobility of 1.2 cm(2)
      V(-1)s(-1) within a 2 V operation and are stable even after exposure to
      conditions typically used for medical sterilization.

PMID- 22395615
TI  - Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated
      acquired B-RAF inhibitor resistance.
AB  - The development of acquired drug resistance hampers the long-term success of B
      RAF inhibitor therapy for melanoma patients. Here we show (V600E)B-RAF copy
      number gain as a mechanism of acquired B-RAF inhibitor resistance in 4 out of 20
      (20%) patients treated with B-RAF inhibitor. In cell lines, (V600E)B-RAF
      overexpression and knockdown conferred B-RAF inhibitor resistance and
      sensitivity, respectively. In (V600E)B-RAF amplification-driven (versus mutant N
      RAS-driven) B-RAF inhibitor resistance, extracellular signal-regulated kinase
      reactivation is saturable, with higher doses of vemurafenib down-regulating
      phosho-extracellular signal-regulated kinase and re-sensitizing melanoma cells to
      B-RAF inhibitor. These two mechanisms of extracellular signal-regulated kinase
      reactivation are sensitive to the MEK1/2 inhibitor AZD6244/selumetinib or its
      combination with the B-RAF inhibitor vemurafenib. In contrast to mutant N-RAS
      mediated (V600E)B-RAF bypass, which is sensitive to C-RAF knockdown, (V600E)B-RAF
      amplification-mediated resistance functions largely independently of C-RAF. Thus,
      alternative clinical strategies may potentially overcome distinct modes of
      extracellular signal-regulated kinase reactivation underlying acquired B-RAF
      inhibitor resistance in melanoma.

PMID- 22395617
TI  - Power laws reveal phase transitions in landscape controls of fire regimes.
AB  - Understanding the environmental controls on historical wildfires, and how they
      changed across spatial scales, is difficult because there are no surviving
      explicit records of either weather or vegetation (fuels). Here we show how power
      laws associated with fire-event time series arise in limited domains of
      parameters that represent critical transitions in the controls on landscape fire.
      Comparison to a self-organized criticality model shows that the latter mimics
      historical fire only in a limited domain of criticality, and is not an adequate
      mechanism to explain landscape fire dynamics, which are shaped by both endogenous
      and exogenous controls. Our results identify a continuous phase transition in
      landscape controls, marked by power laws, and provide an ecological analogue to
      critical behaviour in physical and chemical systems. This explicitly cross-scale
      analysis provides a paradigm for identifying critical thresholds in landscape
      dynamics that may be crossed in a rapidly changing climate.

PMID- 22395616
TI  - Self-assembly of amorphous calcium carbonate microlens arrays.
AB  - Biological materials are often based on simple constituents and grown by the
      principle of self-assembly under ambient conditions. In particular,
      biomineralization approaches exploit efficient pathways of inorganic material
      synthesis. There is still a large gap between the complexity of natural systems
      and the practical utilization of bioinspired formation mechanisms. Here we
      describe a simple self-assembly route leading to a CaCO(3) microlens array,
      somewhat reminiscent of the brittlestars' microlenses, with uniform size and
      focal length, by using a minimum number of components and equipment at ambient
      conditions. The formation mechanism of the amorphous CaCO(3) microlens arrays was
      elucidated by confocal Raman spectroscopic imaging to be a two-step growth
      process mediated by the organic surfactant. CaCO(3) microlens arrays are easy to
      fabricate, biocompatible and functional in amorphous or more stable crystalline
      forms. This shows that advanced optical materials can be generated by a simple
      mineral precipitation.

PMID- 22395618
TI  - Room temperature ferromagnetism in Teflon due to carbon dangling bonds.
AB  - The ferromagnetism in many carbon nanostructures is attributed to carbon dangling
      bonds or vacancies. This provides opportunities to develop new functional
      materials, such as molecular and polymeric ferromagnets and organic spintronic
      materials, without magnetic elements (for example, 3d and 4f metals). Here we
      report the observation of room temperature ferromagnetism in Teflon tape
      (polytetrafluoroethylene) subjected to simple mechanical stretching, cutting or
      heating. First-principles calculations indicate that the room temperature
      ferromagnetism originates from carbon dangling bonds and strong ferromagnetic
      coupling between them. Room temperature ferromagnetism has also been successfully
      realized in another polymer, polyethylene, through cutting and stretching. Our
      findings suggest that ferromagnetism due to networks of carbon dangling bonds can
      arise in polymers and carbon-based molecular materials.

PMID- 22395619
TI  - Microwave cavity-enhanced transduction for plug and play nanomechanics at room
      temperature.
AB  - Following recent insights into energy storage and loss mechanisms in
      nanoelectromechanical systems (NEMS), nanomechanical resonators with increasingly
      high quality factors are possible. Consequently, efficient, non-dissipative
      transduction schemes are required to avoid the dominating influence of coupling
      losses. Here we present an integrated NEMS transducer based on a microwave cavity
      dielectrically coupled to an array of doubly clamped pre-stressed silicon nitride
      beam resonators. This cavity-enhanced detection scheme allows resolving of the
      resonators' Brownian motion at room temperature while preserving their high
      mechanical quality factor of 290,000 at 6.6 MHz. Furthermore, our approach
      constitutes an 'opto'-mechanical system in which backaction effects of the
      microwave field are employed to alter the effective damping of the resonators. In
      particular, cavity-pumped self-oscillation yields a linewidth of only 5 Hz.
      Thereby, an adjustement-free, all-integrated and self-driven
      nanoelectromechanical resonator array interfaced by just two microwave connectors
      is realised, which is potentially useful for applications in sensing and signal
      processing.

PMID- 22395620
TI  - Charge state manipulation of qubits in diamond.
AB  - The nitrogen-vacancy (NV) centre in diamond is a promising candidate for a solid
      state qubit. However, its charge state is known to be unstable, discharging from
      the qubit state NV(-) into the neutral state NV(0) under various circumstances.
      Here we demonstrate that the charge state can be controlled by an electrolytic
      gate electrode. This way, single centres can be switched from an unknown non
      fluorescent state into the neutral charge state NV(0), and the population of an
      ensemble of centres can be shifted from NV(0) to NV(-). Numerical simulations
      confirm the manipulation of the charge state to be induced by the gate-controlled
      shift of the Fermi level at the diamond surface. This result opens the way to a
      dynamic control of transitions between charge states and to explore hitherto
      inaccessible states, such as NV(+).

PMID- 22395621
TI  - Ptychographic electron microscopy using high-angle dark-field scattering for sub
      nanometre resolution imaging.
AB  - Diffractive imaging, in which image-forming optics are replaced by an inverse
      computation using scattered intensity data, could, in principle, realize
      wavelength-scale resolution in a transmission electron microscope. However, to
      date all implementations of this approach have suffered from various experimental
      restrictions. Here we demonstrate a form of diffractive imaging that unshackles
      the image formation process from the constraints of electron optics, improving
      resolution over that of the lens used by a factor of five and showing for the
      first time that it is possible to recover the complex exit wave (in modulus and
      phase) at atomic resolution, over an unlimited field of view, using low-energy
      (30 keV) electrons. Our method, called electron ptychography, has no fundamental
      experimental boundaries: further development of this proof-of-principle could
      revolutionize sub-atomic scale transmission imaging.

PMID- 22395622
TI  - Categories of advanced-technology IOLs: overview.

PMID- 22395623
TI  - Different categories of advance technology IOLs and pearls to consider when
      matching personality profile with IOL selection.

PMID- 22395624
TI  - Management of astigmatism:  toric intraocular lenses.

PMID- 22395625
TI  - Management of astigmatism: LRIs.

PMID- 22395626
TI  - Review of presbyopic IOLs: multifocal and accommodating IOLs.

PMID- 22395627
TI  - Top 5 pearls to consider when implanting advanced-technology IOLs in patients
      with ocular surface disease.

PMID- 22395628
TI  - Top 5 pearls to consider when implanting advanced-technology IOLs in patients
      with a compromised cornea.

PMID- 22395629
TI  - Top 5 pearls for implanting premium IOLs in patients with glaucoma.

PMID- 22395630
TI  - Cataract surgery and intraocular lens selection in patients with age-related
      macular degeneration: pearls for success.

PMID- 22395631
TI  - Top 5 pearls to consider when implanting advanced technology IOLs in patients
      with unusual circumstances.

PMID- 22395632
TI  - Advanced technology IOLs in cataract surgery: management of the unhappy patient.

PMID- 22395633
TI  - Advanced technology IOLs in cataract surgery: pearls for successful femtosecond
      cataract surgery.

PMID- 22395636
TI  - Advanced technology intraocular lasers (IOLs) in cataract surgery. Preface.

PMID- 22395637
TI  - Context-based electronic health record: toward patient specific healthcare.
AB  - Due to the increasingly data-intensive clinical environment, physicians now have
      unprecedented access to detailed clinical information from a multitude of
      sources. However, applying this information to guide medical decisions for a
      specific patient case remains challenging. One issue is related to presenting
      information to the practitioner: displaying a large (irrelevant) amount of
      information often leads to information overload. Next-generation interfaces for
      the electronic health record (EHR) should not only make patient data easily
      searchable and accessible, but also synthesize fragments of evidence documented
      in the entire record to understand the etiology of a disease and its clinical
      manifestation in individual patients. In this paper, we describe our efforts
      toward creating a context-based EHR, which employs biomedical ontologies and
      (graphical) disease models as sources of domain knowledge to identify relevant
      parts of the record to display. We hypothesize that knowledge (e.g., variables,
      relationships) from these sources can be used to standardize, annotate, and
      contextualize information from the patient record, improving access to relevant
      parts of the record and informing medical decision making. To achieve this goal,
      we describe a framework that aggregates and extracts findings and attributes from
      free-text clinical reports, maps findings to concepts in available knowledge
      sources, and generates a tailored presentation of the record based on the
      information needs of the user. We have implemented this framework in a system
      called Adaptive EHR, demonstrating its capabilities to present and synthesize
      information from neurooncology patients. This paper highlights the challenges and
      potential applications of leveraging disease models to improve the access,
      integration, and interpretation of clinical patient data.

PMID- 22395638
TI  - Prevalence of primary headaches in Germany: results of the German Headache
      Consortium Study.
AB  - We investigated the prevalence of migraine (MIG), tension-type headache (TTH),
      and chronic headache in a population-based sample in Germany. A total of 18,000
      subjects aged between 18 and 65 years were screened from 2003 until 2005 using a
      validated questionnaire. Overall 9,944 participants (55.2%) responded (mean age
      43 +/- 13.1 years, 52.7% women). Headache frequency <15 days/month was reported
      by 5,350 (55.5%) subjects of whom 1,601 (16.6%, [95% confidence interval (95%
      CI): 15.9-17.4]) reported episodic MIG, 1,202 (12.5%, 95% CI 11.8-13.1) episodic
      TTH, and 1,150 (11.9%, [11.3-12.6]) episodic MIG + episodic TTH, 1,396 (14.5%,
      [13.8-15.2]) unclassifiable headache. In women, episodic MIG peaked between 36
      and 40 years, episodic MIG + TTH between 18 and 35 years and episodic TTH between
      56 and 66 years. In men, episodic MIG was predominant between 36 and 45 years,
      episodic MIG + TTH between 26 and 35 years and episodic TTH showed comparable
      frequency between 36 and 66 years. Headache >=15 days/month was reported by 2.6%
      (n = 255, [95% CI 2.3-3]). Chronic MIG was reported by 1.1% (n = 108, [0.91
      1.33]), chronic TTH (n = 50, [95% CI 0.4-0.7]), chronic MIG + TTH 0.8% (n = 74,
      95% CI 0.6-0.9) and unclassifiable headache 0.2% (n = 23, [95% CI 0.1-0.3]).
      Chronic headache was more frequent in women compared to men with the highest
      prevalence between 46 and 65 years. It is of note that the number of subjects
      with chronic headache is small in all age groups. The results of our large,
      population-based study provide reliable, age- and sex-specific estimates of the
      prevalence of primary headache disorders in Germany. The prevalence with respect
      to episodic and chronic primary headache disorders in Germany is comparable to
      other European countries and the USA.

PMID- 22395639
TI  - Results of a patient survey for an implantable neurostimulator to treat migraine
      headaches.
AB  - Migraine attacks are believed to involve activation of the trigeminovascular
      system and trigeminal-parasympathetic reflex, which is mediated through the
      sphenopalatine ganglion (SPG). An implantable SPG neurostimulator has been
      developed to apply on-demand SPG stimulation for the treatment of severe primary
      headache. The neurostimulator is implanted via an oral incision and placed along
      the maxilla, with the lead placed at the SPG. The neurostimulator contains no
      battery and is powered and controlled via a handheld remote controller. The
      potential interest of patients with high-frequency, high-disability migraine in
      having a SPG neurostimulator implanted to treat migraine is unknown. We aimed to
      evaluate patient interest to undergo such an implantation procedure and to
      participate in a clinical investigation of on-demand SPG stimulation for migraine
      by conducting a survey at the Ghent University Hospital in 41 migraineurs.
      Seventy-seven percent (77%) of subjects expressed an interest in participating in
      a clinical investigation requiring implantation of a SPG neurostimulator when
      headache frequency and severity were considered and 69% when pain relief
      experienced with current migraine treatment was considered. Preventive and acute
      medications were used in 64 and 95% of the subjects, respectively, and provided a
      reported reduction of headache frequency, duration and pain. However, acute
      medications were frequently associated with headache recurrence and bothersome
      side effects. Results indicate that a majority of high-frequency, high-disability
      migraineurs, many of whom achieve pain relief with their current medications,
      have an interest in participating in a clinical investigation of an implantable
      SPG neurostimulator for the treatment of migraine headache.

PMID- 22395640
TI  - Nb2O5 as a new electron transport layer for double junction polymer solar cells.
AB  - Nb(2)O(5) as a new electron transport layer (ETL) was used for double junction
      polymer solar cells. The Nb(2)O(5) ETL was prepared by spin coating a Nb(2)O(5)
      sol-gel solution onto the active layer of the optical front subcell. The double
      junction devices using Nb(2)O(5) ETL exhibit an open circuit voltage (V(oc)) of
      1.30 V, which is close to the sum of the s of the individual subcells. The
      current density-voltage (J-V) simulation showed that the double junction device
      performance using Nb(2)O(5) as ETL could be significantly increased by reducing
      the series resistance (R(se)) and matching the current densities of the
      individual subcells.

PMID- 22395641
TI  - Therapeutic cancer vaccines: current status and moving forward.
AB  - Concurrent with U.S. Food and Drug Administration (FDA) approval of the first
      therapeutic cancer vaccine, a wide spectrum of other cancer vaccine platforms
      that target a diverse range of tumor-associated antigens is currently being
      evaluated in randomized phase II and phase III trials. The profound influence of
      the tumor microenvironment and other immunosuppressive entities, however, can
      limit the effectiveness of these vaccines. Numerous strategies are currently
      being evaluated both preclinically and clinically to counteract these
      immunosuppressive entities, including the combined use of vaccines with immune
      checkpoint inhibitors, certain chemotherapeutics, small-molecule targeted
      therapies, and radiation. The potential influence of the appropriate patient
      population and clinical trial endpoint in vaccine therapy studies is discussed,
      as well as the potential importance of biomarkers in future directions of this
      field.

PMID- 22395642
TI  - Clinical outcome prediction by microRNAs in human cancer: a systematic review.
AB  - BACKGROUND: MicroRNA (miR) expression may have prognostic value for many types of
      cancers. However, the miR literature comprises many small studies. We
      systematically reviewed and synthesized the evidence. METHODS: Using MEDLINE
      (last update December 2010), we identified English language studies that examined
      associations between miRs and cancer prognosis using tumor specimens for more
      than 10 patients during classifier development. We included studies that assessed
      a major clinical outcome (nodal disease, disease progression, response to
      therapy, metastasis, recurrence, or overall survival) in an agnostic fashion
      using either polymerase chain reaction or hybridized oligonucleotide microarrays.
      RESULTS: Forty-six articles presenting results on 43 studies pertaining to 20
      different types of malignancy were eligible for inclusion in this review. The
      median study size was 65 patients (interquartile range [IQR] = 34-129), the
      median number of miRs assayed was 328 (IQR = 250-470), and overall survival or
      recurrence were the most commonly measured outcomes (30 and 19 studies,
      respectively). External validation was performed in 21 studies, 20 of which
      reported at least one nominally statistically significant result for a miR
      classifier. The median hazard ratio for poor outcome in externally validated
      studies was 2.52 (IQR = 2.26-5.40). For all classifier miRs in studies that
      evaluated overall survival across diverse malignancies, the miRs most frequently
      associated with poor outcome after accounting for differences in miR assessment
      due to platform type were let-7 (decreased expression in patients with cancer)
      and miR 21 (increased expression). CONCLUSIONS: MiR classifiers show promising
      prognostic associations with major cancer outcomes and specific miRs are
      consistently identified across diverse studies and platforms. These types of
      classifiers require careful external validation in large groups of cancer
      patients that have adequate protection from bias. -

PMID- 22395643
TI  - CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast
      cancer patients.
AB  - BACKGROUND: Adjuvant tamoxifen therapy substantially decreases the risk of
      recurrence and mortality in women with hormone (estrogen and/or progesterone)
      receptor-positive breast cancer. Previous studies have suggested that metabolic
      conversion of tamoxifen to endoxifen by cytochrome P450 2D6 (CYP2D6) is required
      for patient benefit from tamoxifen therapy. METHODS: Tumor specimens from a
      subset of postmenopausal patients with hormone receptor-positive early-stage
      (stages I, II, and IIIA) breast cancer, who were enrolled in the randomized
      double-blind Arimidex, Tamoxifen, Alone or in Combination (ATAC) clinical trial,
      were genotyped for variants in CYP2D6 (N = 1203 patients: anastrozole [trade
      name: Arimidex] group, n = 615 patients; tamoxifen group, n = 588 patients) and
      UDP-glucuronosyltransferase-2B7 (UGT2B7), whose gene product inactivates
      endoxifen (N = 1209 patients; anastrozole group, n = 606 patients; tamoxifen
      group, n = 603 patients). Genotyping was performed using polymerase chain
      reaction-based TaqMan assays. Based on the genotypes for CYP2D6, patients were
      classified as poor metabolizer (PM), intermediate metabolizer (IM), or extensive
      metabolizer (EM) phenotypes. We evaluated the association of CYP2D6 and UGT2B7
      genotype with distant recurrence (primary endpoint) and any recurrence (secondary
      endpoint) by estimating the hazard ratios (HRs) and corresponding 95% confidence
      intervals (CIs) using Cox proportional hazards models. All statistical tests were
      two-sided. RESULTS: After a median follow-up of 10 years, no statistically
      significant associations were observed between CYP2D6 genotype and recurrence in
      tamoxifen-treated patients (PM vs EM: HR for distant recurrence = 1.25, 95% CI =
      0.55 to 3.15, P = .64; HR for any recurrence = 0.99, 95% CI = 0.48 to 2.08, P =
      .99). A near-null association was observed between UGT2B7 genotype and recurrence
      in tamoxifen-treated patients. No associations were observed between CYP2D6 and
      UGT2B7 genotypes and recurrence in anastrozole-treated patients. CONCLUSION: The
      results do not support the hypothesis that CYP2D6 genotype predicts clinical
      benefit of adjuvant tamoxifen treatment among postmenopausal breast cancer
      patients.

PMID- 22395645
TI  - CYP2D6 genotype as a marker for benefit of adjuvant tamoxifen in postmenopausal
      women: lessons learned.

PMID- 22395644
TI  - CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine
      responsive breast cancer: the breast international group 1-98 trial.
AB  - BACKGROUND: Adjuvant tamoxifen therapy is effective for postmenopausal women with
      endocrine-responsive breast cancer. Cytochrome P450 2D6 (CYP2D6) enzyme
      metabolizes tamoxifen to clinically active metabolites, and CYP2D6 polymorphisms
      may adversely affect tamoxifen efficacy. In this study, we investigated the
      clinical relevance of CYP2D6 polymorphisms. METHODS: We obtained tumor tissues
      and isolated DNA from 4861 of 8010 postmenopausal women with hormone receptor
      positive breast cancer who enrolled in the randomized, phase III double-blind
      Breast International Group (BIG) 1-98 trial between March 1998 and May 2003 and
      received tamoxifen and/or letrozole treatment. Extracted DNA was used for
      genotyping nine CYP2D6 single-nucleotide polymorphisms using polymerase chain
      reaction-based methods. Genotype combinations were used to categorize CYP2D6
      metabolism phenotypes as poor, intermediate, and extensive metabolizers (PM, IM,
      and EM, respectively; n = 4393 patients). Associations of CYP2D6 metabolism
      phenotypes with breast cancer-free interval (referred to as recurrence) and
      treatment-induced hot flushes according to randomized endocrine treatment and
      previous chemotherapy were assessed. Cox proportional hazards models were used to
      calculate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical
      tests were two-sided. RESULTS: No association between CYP2D6 metabolism
      phenotypes and breast cancer-free interval was observed among patients who
      received tamoxifen monotherapy without previous chemotherapy (P = .35). PM or IM
      phenotype had a non-statistically significantly reduced risk of breast cancer
      recurrence compared with EM phenotype (PM or IM vs EM, HR of recurrence = 0.86,
      95% CI = 0.60 to 1.24). CYP2D6 metabolism phenotype was associated with tamoxifen
      induced hot flushes (P = .020). Both PM and IM phenotypes had an increased risk
      of tamoxifen-induced hot flushes compared with EM phenotype (PM vs EM, HR of hot
      flushes = 1.24, 95% CI = 0.96 to 1.59; IM vs EM, HR of hot flushes = 1.23, 95% CI
      = 1.05 to 1.43). CONCLUSIONS: CYP2D6 phenotypes of reduced enzyme activity were
      not associated with worse disease control but were associated with increased hot
      flushes, contrary to the hypothesis. The results of this study do not support
      using the presence or absence of hot flushes or the pharmacogenetic testing of
      CYP2D6 to determine whether to treat postmenopausal breast cancer patients with
      tamoxifen.

PMID- 22395646
TI  - Odd-electron molecular theory of graphene hydrogenation.
AB  - This paper highlights the molecular essence of graphene and presents its
      hydrogenation from the viewpoint of the odd-electron molecular theory. This
      chemical transformation was performed computationally, using a particular
      algorithm, through the stepwise addition of either hydrogen molecules or hydrogen
      atoms to a pristine graphene molecule. The graphene was considered to be a
      membrane, such that either both sides or just one side of the membrane was
      accessible to adsorbate, and the atoms on the perimeter of the membrane were
      either fixed (fixed membrane) or free to move (free-standing membrane). The
      algorithm explored the spatial distribution of the number of effectively unpaired
      electrons N (DA) over the carbon skeleton of the molecule. The highest ranked N
      (DA) values were considered to indicate the target atoms at each reaction step.
      The dependence of the hydrogenation itself and the final graphene hydrides on
      external factors such as whether the membrane was fixed, if both sides or only
      one side of the membrane were accessible to hydrogen, and whether the hydrogen
      was in the molecular or atomic state. Complete hydrogenation followed by the
      formation of a regular chairlike graphane structure (CH)(n) was only found to be
      possible for a fixed pristine graphene membrane for which the basal plane is
      accessible to hydrogen atoms from both sides.

PMID- 22395647
TI  - Selective oxidation of propylamine on oxygen-covered Au(111): a DFT study.
AB  - The reaction mechanism for selective oxidation of propylamine on oxygen-covered
      gold has been studied by the density functional theory (DFT) and generalized
      gradient approximation (GGA) with slab model. Our calculation results indicated
      that the adsorption energy of propylamine decreases with the increasing oxygen
      coverage, that is -0.38, -0.20 and -0.10 eV on clean, 2/9 monolayer (ML) and 2/3
      monolayer (ML) oxygen, respectively. The adsorption energies of the intermediates
      also have the trend of the gradual lower. The present work also indicated that
      the final product distribution depends on the oxygen coverage: propylamine
      undergoes N-H bond and C-H bond cleavage to produce propionitrile and water at
      low-oxygen-coverage (theta(o) = 2/9 ML), and to yield propionitrile,
      propionaldehyde and water at high-oxygen-coverage (theta(o) = 2/3 ML). The energy
      barrier of the first step of propyamine oxidation (CH(3)CH(2)CH(2)NH(2) ->
      CH(3)CH(2)CH(2)NH) is 0.16 eV (theta(o) = 2/9 ML) and 0.38 eV (theta(o) = 2/3
      ML). On the second step, the barrier energy is 0.16 (theta(o) = 2/9 ML) and 0.25
      (theta(o) = 2/3 ML) eV of CH(3)CH(2)CH(2)NH -> CH(3)CH(2)CH(2)N, next both C-H
      breakage and the barrier energy is 0.20 eV (CH(3)CH(2)CH(2)N -> CH(3)CH(2)CHN)
      and 0.25 eV (CH(3)CH(2)CHN -> CH(3)CH(2)CN) on low oxygen coverage, and 0.15 eV
      (CH(3)CH(2)CH(2)N -> CH(3)CH(2)CHN) and 0.26 eV(CH(3)CH(2)CHN -> CH(3)CH(2)CN) on
      the high oxygen coverage. The additional reaction step of CH(3)CH(2)CHN ->
      CH(3)CH(2)CHO occurs on the high oxygen coverage, and the associated barrier is
      0.41 eV. The calculation results show that the oxidation of propylamine can occur
      at room temperature due to the lower energy barrier. Furthermore, it was found
      that the energy barrier for the possible reaction steps at the low oxygen
      coverage is generally smaller than that on high oxygen coverage, which agrees
      with the experimental results.

PMID- 22395648
TI  - Local and global effects of Mg2+ on Ago and miRNA-target interactions.
AB  - Three magnesium ions (Mg(2+)), named Mg1 (in Mid domain), Mg2 and Mg3 (both in
      PIWI domain), located at the small RNA binding domain of Argonaute (Ago) protein,
      are important for sequence-specific miRNA-target interactions. Such conjunction
      between the Ago protein and miRNA raises the question: How do Mg(2+) ions
      participate in the recognition process of miRNA by Ago or its target.
      Furthermore, it is still unclear whether the Mg(2+) ions contribute to the local
      or global stability of the miRNA complex. In this work, we have performed a
      series of 16 independent molecular dynamic simulations (MD) to characterize the
      functions of Mg(2+), hydration patterns and the conformational events involved in
      the miRNA-target interactions. The cross correlation analysis shows that Mg1 and
      Mg2 significantly enhance a locally cooperated movement of the PAZ, PIWI and Mid
      domains with the average correlation coefficient of ~0.65, producing an "open
      closed" motion (rotation Angle, 46.5 degrees ) between the PAZ and PIWI domains.
      Binding of Mg3 can globally stabilize the whole Ago protein with the average RMSD
      of ~0.34 A, compared with the systems in absence of Mg3 (average RMSD = ~0.43 A).
      Three structural water molecules surrounding the Mg(2+)-binding regions also
      stabilize these ions, thus facilitating the recognition of miRNA to its target.
      In addition, the thermodynamic analysis also verifies the positive contribution
      of all three Mg(2+) to the binding of miRNA to Ago, as well as the importance Mg2
      plays in the cleavage of the miRNA targets.

PMID- 22395649
TI  - Study on the enantioselectivity inhibition mechanism of acetyl-coenzyme A
      carboxylase toward haloxyfop by homology modeling and MM-PBSA analysis.
AB  - Acetyl-coenzyme A carboxylase (ACCase) has been identified as one of the most
      important targets of herbicide Aryloxyphenoxypropionates (APPs). ACCase shows
      different enantioselectivity toward APPs, and only (R)-enantiomers of APPs have
      the herbicidal activity. In order to deeply understand the enantioselective
      recognition mechanism of ACCase, (R)-haloxyfop, which is a typical commercial
      herbicide from APPs, is selected and the relative binding free energy between
      ACCase and (R)-haloxyfop is investigated and compared with that between ACCase
      and (S)-haloxyfop by homology modeling and molecular mechanics-Poisson-Boltzmann
      surface area (MM-PBSA) method. Further free energy analysis reveals that the
      preference of ACCase toward (R)-haloxyfop is mainly driven by Van der Waals
      interaction. The analysis of the interaction between the active site residues of
      ACCase CT domain and (R)-haloxyfop shows the van der Waals interactions have a
      close relationship with the addition effect of each residue. An understanding of
      the enantioselective recognition mechanism between ACCase and haloxyfop is
      desirable to discover novel chiral herbicides.

PMID- 22395651
TI  - Prolonged sinoatrial block in an infant with respiratory syncytial viral
      bronchiolitis.
AB  - Complete heart block in children admitted to the pediatric intensive care unit
      with respiratory syncytial viral (RSV) infections has been described. This report
      describes a prolonged sinoatrial block exceeding 4 s in an infant with RSV,
      which, to the authors' knowledge, is the longest such event described in the
      published literature. This block was followed by shorter episodes within the next
      24 h. An extensive workup showed no other known cause of bradycardia or
      sinoatrial block. The infant was discharged home with 48 h Holter monitoring,
      which was normal. At this writing, the infant has remained asymptomatic since
      discharge. Respiratory syncytial viral infections may cause prolonged sinoatrial
      block in an otherwise healthy child.

PMID- 22395650
TI  - Ontogeny of cardiac sympathetic innervation and its implications for cardiac
      disease.
AB  - The vertebrate heart is innervated by the sympathetic and parasympathetic
      components of the peripheral autonomic nervous system, which regulates its
      contractile rate and force. Understanding the mechanisms that control sympathetic
      neuronal growth, differentiation, and innervation of the heart may provide
      insight into the etiology of cardiac arrhythmogenesis. This review provides an
      overview of the cell signaling pathways and transcriptional effectors that
      regulate both the noradrenergic gene program during sympathetic neurogenesis and
      regional nerve density during cardiac innervation. Recent studies exploring
      transcriptional regulation of the bHLH transcription factor Hand1 in developing
      sympathetic neurons are explored, and how the Hand1 sympathetic neuron-specific
      cis-regulatory element may be used further to assess the contribution of altered
      sympathetic innervation to human cardiac disease is discussed.

PMID- 22395653
TI  - A huge malodorous lesion on the scalp.

PMID- 22395654
TI  - Broad cortical activation in response to tactile stimulation in newborns.
AB  - Tactile sensation, which is one of the earliest developing sensory systems, is
      very important in the perception of an individual's body and the surrounding
      physical environment, especially in newborns. However, currently, only little is
      known about the response of a newborn's brain to tactile sensation. The objective
      of the present study was to determine the response of a newborn's brain to
      tactile sensation and to compare the brain responses to various sensory stimuli.
      Ten healthy newborns, 2-9 days after birth, were enrolled. A multichannel near
      infrared spectroscopy system was used to measure brain responses. The probe array
      covered broad cortical areas, including the parietal, temporal, and occipital
      areas. We measured cortical hemodynamic changes in response to three different
      types of stimuli: tactile, auditory, and visual. Activated areas were analyzed by
      t-tests, and the number of activated channels among the three different stimuli
      was compared by chi2-tests. The results showed that when the brain responded to
      each type of stimulation, the corresponding primary sensory area was activated,
      and tactile stimuli induced broader areas of brain activation than the other two
      types of stimuli (auditory or visual). Thus, broad brain areas, including the
      temporal and parietal areas, were activated by tactile stimuli in early newborn
      periods. These results suggest that there are differences in newborns' reactions
      to various types of sensory stimuli, which may reflect the importance of tactile
      sensation in the early newborn period.

PMID- 22395655
TI  - Stimulation of the subthalamic nucleus improves velocity of ballistic movements
      in Parkinson's disease.
AB  - High-frequency stimulation of the subthalamic nucleus can markedly improve motor
      function in patients with Parkinson's disease. However, the underlying mechanisms
      mediating these improvements are not well understood. In particular, whether
      motor function is differentially improved in distal or proximal movements is not
      fully determined. Also, whether reaction time is improved along with other motor
      parameters is still a matter of debate. Here, we test patients OFF and ON
      subthalamic nucleus stimulation by capturing simple ballistic movements across
      four joints using kinematic motion analysis. We show that velocity, but not
      reaction time, is significantly improved with stimulation. There was no strong
      differential effect between joints. These results add evidence that deep brain
      stimulation of the subthalamic nucleus can enhance performance of ballistic
      movements in Parkinson's disease, and demonstrate that the subthalamic nucleus
      may be important in driving parameters of motor control after the response has
      been initiated.

PMID- 22395656
TI  - Paraventricular nucleus anandamide signaling alters eating and substrate
      oxidation.
AB  - In the central nervous system, the endocannabinoid anandamide [N
      arachidonoylethanolamine (AEA)] is believed to increase food intake through on
      demand activation of hypothalamic circuits. The present study examined the
      effects of hypothalamic paraventricular nucleus (PVN) injections of AEA (25-400
      pmol) on food intake and energy substrate oxidation [respiratory quotient (RQ)].
      PVN administration of AEA increased eating behavior and RQ, indicating enhanced
      carbohydrate oxidation. Further, PVN administration of the cannabinoid type 1
      receptor inverse agonist AM251 (5-10 MUg) attenuated both the eating and the RQ
      responses elicited by AEA (100 pmol). AM251 administered alone did not alter food
      intake or RQ. Overall, these findings are consistent with a role for PVN
      cannabinoid type 1 receptors in the regulation of eating and energy homeostasis.

PMID- 22395657
TI  - The role of monetary incentives in feedback processing:  why we should pay our
      participants.
AB  - Performance monitoring has been associated with two event-related potentials. The
      feedback-related negativity reflects a reinforcement-learning signal leading to
      remedial action, whereas the P3 reflects the motivational significance of
      feedback outcomes. Till date, research has focused on how these components are
      influenced by different outcomes within a range of the same, usually monetary,
      feedback type. This study examined how different feedback types (monetary vs.
      nonmonetary) influence these two components. Participants performed a time
      estimation task under a monetary and a nonmonetary condition. Larger feedback
      related negativities, better overall performance, and smaller behavioral
      adjustments were found under the monetary condition. Larger P3 amplitudes were
      present under the monetary condition and in response to positive outcomes.
      Condition order influenced only the P3. Addition of financial incentives
      increased the P3 amplitude, whereas removal of financial incentives did not alter
      the P3 amplitude. The results suggest that individuals were more reluctant to
      commit errors under the monetary condition as evidenced by more pronounced
      reinforcement-learning signals and better overall performance. Positive outcomes
      under this condition were most salient as indicated by larger P3s.

PMID- 22395658
TI  - Underutilisation of the gastroscope for total colonoscopy in adults: a survey of
      two European countries.
AB  - BACKGROUND AND STUDY AIMS: High caecal intubation success rates have been
      reported with the gastroscope in adults. We surveyed the current use of the
      gastroscope for total colonoscopy in adults in the UK and Greece. METHODS: A
      questionnaire was e-mailed to 952 members of the British Society of
      Gastroenterology (UK) and 478 members of the Hellenic Society of Gastroenterology
      (GR), enquiring as to access to a paediatric colonoscope, use of gastroscope for
      total colonoscopy and estimate of caecal intubation success rate. RESULTS: Valid
      replies were 17.4% from UK and 19.7% from GR. The paediatric colonoscope was
      available to 106/138 (77%) UK and to only 18/86 (21%) GR respondents (p =
      0.0002). Of all the UK and GR respondents, 109/138 (79%) and 68/86 (79%),
      respectively, did not use the gastroscope for total colonoscopy. For the use of
      the gastroscope for total colonoscopy, 26/29 (89%) UK and 9/18 (50%) GR users did
      so, while a paediatric colonoscope was also available (p = 0.001), and 3/29
      (10.3%) UK and 9/18 (50%) GR users did so, whilst they had no access to a
      paediatric colonoscope (p = 0.001). Estimated gastroscope caecal intubation
      success rate was 69% (SD 0.26) UK and 46% (SD 0.36) GR, p = 0.008. Only 37% UK
      and 28% GR respondents used the gastroscope to examine the left colon.
      CONCLUSIONS: The gastroscope is underutilised for total colonoscopy in both the
      UK and Greece. Use of the gastroscope does not appear to be related to lack of
      access to a paediatric colonoscope in the UK but may be in GR. Gastroscope caecal
      intubation success rate justifies its use where the colonoscope fails.

PMID- 22395659
TI  - Increased use of multidisciplinary treatment modalities adds little to the
      outcome of rectal cancer treated by optimal total mesorectal excision.
AB  - PURPOSE: Total mesorectal excision (TME) is the standard surgical treatment for
      rectal cancer. The roles of chemotherapy and radiotherapy have become more
      defined, accompanied by improvements in preoperative staging and
      histopathological assessment. We analyse our ongoing results in the light of
      changing patterns of treatment over consecutive time periods. METHODS: In total,
      151 consecutive patients underwent potentially curative rectal excision for
      cancer in a single institution. Management and outcomes were compared between
      1993-1999 and 2000-2007 which corresponded with the restructuring of the regional
      oncological services. RESULTS: We found an increase in patients treated with
      neoadjuvant chemoradiotherapy after 1999 (20/89 vs 1/62, p < 0.001). There was an
      increase in the mean number of lymph nodes examined (11.9 vs 9.4, p = 0.037). The
      locoregional recurrence rate was 5.3%. The rates were not significantly different
      between the two study periods [4/89 (4.5%) 1999-2007 vs 4/62 (6.5%) 1993-1999, p
      = 0.597]. There was no statistical difference in overall or disease-free survival
      in the time periods examined. CONCLUSIONS: Increasing use of neoadjuvant therapy
      and concomitant improvement in lymph node assessment did not translate into a
      concurrent reduction in the local recurrence, disease-free and overall survival
      rates. Our results demonstrate the enduring benefit of specialist training in TME
      in the outcome of rectal cancer surgery. This observational study suggests that
      low local recurrence rates are surrogate markers for improved overall and disease
      free survival. Multidisciplinary team practice should be examined and made cost
      effective according to the individual unit's local recurrence rate in the light
      of this and other reports.

PMID- 22395662
TI  - Paroxysmal nocturnal hemoglobinuria.
AB  - PURPOSE OF REVIEW: The aim is to report on recent observations related to the
      natural history of paroxysmal nocturnal hemoglobinuria (PNH) and to review new
      therapeutic strategies for controlling the hemolysis of PNH. RECENT FINDINGS:
      This review focuses on studies designed to characterize the long-term outcome of
      patients with PNH treated with eculizumab and to define the relationship between
      PNH and bone marrow failure syndromes. New therapeutic strategies aimed at
      controlling extravascular as well as intravascular hemolysis are also examined.
      SUMMARY: Long-term safety and efficacy of eculizumab was observed in a large
      group of patients. Survival for the group was not different from that of a sex
      matched and age-matched control group from the general population. Thrombotic
      complications were rare and deaths due to PNH or complications of therapy were
      not observed. These studies suggest that patients with clinical PNH who are
      treated with eculizumab have a benign clinical course. Patients with bone marrow
      failure who have PNH cells detected by high-sensitivity flow cytometry have
      aplastic anemia or low-risk myelodysplastic syndrome. For patients with a
      percentage of PNH cells that is below the threshold for producing laboratory
      evidence of hemolysis (subclinical PNH), expansion of the clone to a size
      sufficient to produce clinical PNH is not observed. Approximately 50% of patients
      with bone marrow failure who have clinical evidence of PNH at presentation will
      require PNH-specific therapy. Novel reagents that target the alternative pathway
      of complement C3 convertase are being developed with a goal of inhibiting both
      the extravascular and the intravascular hemolysis of PNH.

PMID- 22395660
TI  - Molecular characterization of Acanthamoeba isolated in water treatment plants and
      comparison with clinical isolates.
AB  - A total of 116 samples (44 clinical specimens and 72 environmental samples) have
      been analyzed for the presence of Acanthamoeba. The environmental samples (ESs)
      were collected from four drinking water treatment plants (DWTP, n=32), seven
      wastewater treatment plants (n=28), and six locations of influence (n=12) on four
      river basins from the central area of Spain (winter-spring 2008). Water samples
      were concentrated by using the IDEXX Filta-Max((r)) system. Acanthamoeba was
      identified in 65 of the 72 ESs by culture isolation (90.3%) and 63 by real-time
      PCR (87.5%), resulting in all sampling points (100%) positive for Acanthamoeba
      when considering both techniques and all the time period analyzed. Nine of the 44
      clinical specimens were positive for Acanthamoeba. Seventeen Acanthamoeba strains
      (eight from four DWTP and nine from clinical samples) were also established in
      axenic-PYG medium. Twenty-four of the ESs and the 17 Acanthamoeba sp. strains
      were genotyped as T4/1, T4/8, and T4/9. The eight strains isolated from the DWTP
      samples were inoculated in nude mouse to ascertain their potential pathogenicity
      in this model. Animals that were inoculated died or showed central nervous system
      symptoms 9 days post-inoculation. Examination of immunofluorescence-stained brain
      and lung tissue sections showed multiple organisms invading both tissues, and re
      isolation of throphozoites was successful in these tissues of all infected
      animals. For the first time, potentially pathogenic Acanthamoeba T4 has been
      detected in 100% of different types of water samples including tap water and
      sewage effluents in the central area of Spain suggesting a potential health
      threat for humans especially for the contact lens wearers.

PMID- 22395661
TI  - Effects of erythropoietin receptors and erythropoiesis-stimulating agents on
      disease progression in cancer.
AB  - Erythropoiesis-stimulating agents (ESAs) increase red blood cell (RBC) production
      in bone marrow by activating the erythropoietin receptor (EpoR) on erythrocytic
      progenitor cells. Erythropoiesis-stimulating agents are approved in the United
      States and Europe for treating anaemia in cancer patients receiving chemotherapy
      based on randomised, placebo-controlled trials showing that ESAs reduce RBC
      transfusions. Erythropoiesis-stimulating agent-safety issues include
      thromboembolic events and concerns regarding whether ESAs increase disease
      progression and/or mortality in cancer patients. Several trials have reported an
      association between ESA use and increased disease progression and/or mortality,
      whereas other trials in the same tumour types have not provided similar findings.
      This review thoroughly examines available evidence regarding whether ESAs affect
      disease progression. Both clinical-trial data on ESAs and disease progression,
      and preclinical data on how ESAs could affect tumour growth are summarised.
      Preclinical topics include (i) whether tumour cells express EpoR and could be
      directly stimulated to grow by ESA exposure and (ii) whether endothelial cells
      express EpoR and could be stimulated by ESA exposure to undergo angiogenesis and
      indirectly promote tumour growth. Although assessment and definition of disease
      progression vary across studies, the current clinical data suggest that ESAs may
      have little effect on disease progression in chemotherapy patients, and
      preclinical data indicate a direct or indirect effect of ESAs on tumour growth is
      not strongly supported.

PMID- 22395663
TI  - Vascular endothelial-cadherin and vascular stability.
AB  - PURPOSE OF REVIEW: Vascular integrity is characterized by a tight control of
      permeability to cells and solutes and by resistance to blood flow. In several
      pathologies including tumor angiogenesis, vascular malformations, hemorrhagic
      stroke and others, there is the need to stabilize the vessels and prevent
      undesired bleeding or edema. Here, we discuss the current knowledge on the role
      of endothelial cell-to-cell adherens junctions in maintaining vascular integrity.
      RECENT FINDINGS: The identification of several components of adherens junctions
      in endothelial cells helped understanding of the complex role of these structures
      not only in maintaining cell-to-cell adhesion but also in transferring
      intracellular signals. Vascular endothelial (VE)-cadherin, an endothelial
      specific adhesion protein at adherens junctions, was found to interact with
      several signaling partners that induce contact inhibition of growth, decrease in
      permeability, tight junction organization and others. Changes in VE-cadherin
      levels in vivo may significantly affect vascular permeability, and induce
      uncontrolled growth and vascular fragility. SUMMARY: In the past years, the
      research on angiogenesis was mostly directed to the definition of the mechanisms
      able to modulate vascular growth. We now understand that in many pathological
      conditions we do not simply need to increase or inhibit vascularization but we
      also need to develop tools able to stabilize organ perfusion and to avoid
      hemorrhages or edema.

PMID- 22395664
TI  - Novel insights into leukocyte extravasation.
AB  - PURPOSE OF REVIEW: Leukocyte extravasation is a multistep process that is
      regulated at various levels. This review will highlight recent findings that
      define new regulatory mechanisms and novel activities in the process of leukocyte
      docking to the endothelium and diapedesis of leukocytes through the endothelial
      barrier of the vessel wall. RECENT FINDINGS: Within the past 2-3 years, novel
      regulatory mechanisms have been identified that control or balance leukocyte
      extravasation at different steps of the extravasation process. First evidence was
      established for differences in the roles of intracellular factors that bind to
      integrins and support their activation. A cytokine was found that counteracts the
      activation of leukocyte integrins. Not only leukocyte integrins but also their
      ligands on endothelial cells were shown to arrange in clusters while supporting
      leukocyte-endothelial interactions. Recent progress was made in determining in
      vivo the route of leukocyte diapedesis through the endothelium of the blood
      vessel wall. Finally, novel mechanisms were found that control the opening of the
      endothelial barrier during diapedesis and others that determine directionality of
      diapedesis. SUMMARY: Recent progress in our understanding of leukocyte
      extravasation has unraveled novel steps and mechanisms that control this process
      in vivo. These findings provide new insights into the mechanisms that balance the
      entry of leukocytes into tissue.

PMID- 22395665
TI  - [Measurement of ocular lens ionizing radiation exposure after radioiodine
      therapy].
AB  - AIM: Current reports for the radiation cataracts contained a warning for
      deterministic effects at 1-2 Gy radiation single exposure for lens. Recently, the
      German Radiation Protection Board (SSK) published a document (234. SSK-Board) in
      that threshold dose for radiation cataracts is claimed at 0.5 Gy. The lens of the
      eye is recognized as one of the most radiosensitive tissues in the human body,
      and the International Commission on Radiological Protection (ICRP 103) has
      defined a limit of 150 mSv for its exposure.Recently, the ICRP lowered this limit
      down to 20 mSv per year.However, this limit does not apply to patients.
      Therefore, the question of the lens radiation exposure for patients underwent a
      radioiodine therapy (RIT) is a point at issue. PATIENTS, METHODS: A total of 41
      patients (age: 22-92 years) underwent a radioiodine therapy were included in the
      study. Optical stimulated luminescence dosimeters were used to measure the
      radiation exposure. The dosimeters were fastened nearby the patient's eye lens.
      The measurement was carried out up to 48 h after radioiodine application and the
      patients were divided into three groups. Group 1: patients underwent a diagnostic
      131I whole body scan (mean activity: 370 MBq); group 2: thyriod carcinoma
      patients under RIT (mean activity: 3700 MBq); group 3: hyperthyroid patients
      under RIT (activity: 180-1237 MBq). RESULTS: The cumulative exposure of the eye
      lens during the stay at the therapy unit (48 h) was 4.8 +/- 0.7 mGy in group 1,
      24.5-50.5 mGy in group 2 and 2.7-26.3 mGy in group 3, respectively. For the
      calculation of the expected cumulative dose, including follow-up after patient's
      dismissal, the effective half-lives were involved. The cumulative doses were
      obtained to be 6 +/- 1 mGy in the first group, 63 +/- 15 mGy in the second and 5
      148 mGy in the third. CONCLUSION: The results show that there exists a low risk
      for radiation cataract in a nuclear medicine therapy unit. After serial
      radioiodine therapies radiation-induced lens opacity cannot be expected.

PMID- 22395667
TI  - Modelling the circularly and linearly polarised spectrum of [Ni(en)3]2+.
AB  - The relative intensity and band shapes of the low energy spin-allowed transitions
      in the linearly polarised and circular dichroism spectrum of [Ni(en)(3)](2+) have
      been calculated using a time-dependent density functional theory approach. The
      effect of the trigonal ligand-field is minimal and no splitting of the bands is
      predicted by the simulations or observed experimentally. The 'd-d' transitions of
      the [Ni(en)(3)](2+) ion are electric dipole allowed but gain much of their
      intensity through Herzberg-Teller vibronic coupling. Its CD spectrum is dominated
      by the low energy band, which gains its rotatory strength through the magnetic
      dipole-allowed character of the parent octahedral transition and the electric
      dipole character due to the trigonal field. The simulation of the spectrum
      incorporates the contribution from all inducing vibrational modes with
      significant involvement of the {NiN(6)} unit. Vibrations which are centred on the
      chelate rings are not important in generating intensity, reflecting the localised
      d-d' character of the transitions. Simulated linearly polarised and circular
      dichroism spectra of such an open-shell system are presented for the first time
      and predict the essential elements of the experimental spectra.

PMID- 22395666
TI  - Diagnostic value of myocardial SPECT to detect in-stent restenosis after drug
      eluting stent implantation.
AB  - Different angiographic patterns and restenosis rate may affect diagnostic value
      of single-photon emission computed tomography (SPECT) in the era of drug-eluting
      stents (DES). We aimed to determine the ability of myocardial SPECT to detect in
      stent restenosis (ISR) in patients treated with DES compared to that of patients
      treated with bare metal stent (BMS). We evaluated 228 consecutive patients who
      underwent 6 months follow-up SPECT and coronary angiography (CAG) after stent
      implantation. In 228 patients, 354 vessels were treated with stent implantation
      (BMS, n = 105; DES, n = 249) and 65 (18.4%) vessels showed ISR (angiographic %
      diameter stenosis >= 50%) at the 6-month follow-up CAG. In patients with BMS-ISR
      (n = 37), restenosis was primarily diffuse (70.3%), whereas patients with DES-ISR
      (n = 28) exhibited more focal restenosis (53.6%, p = 0.028). The sensitivity and
      specificity of myocardial SPECT did not differ significantly between patients
      with BMS and those with DES (BMS vs. DES: sensitivity 56.8 vs. 39.3%, p = 0.163;
      specificity 72.1 vs. 76.5%, p = 0.460). Evaluation of 71 false positive and 33
      false negative lesions showed that the most common cause of false-positive
      results in SPECT was the perfusion decrease which improved but not disappeared
      compared with the baseline (46 among 71 vascular territories). Despite different
      patterns of restenosis and ISR rates, the diagnostic value of SPECT did not
      differ between BMS and DES. Further study looking at ISR in larger number of
      patients and using other protocol such as Fleming-Harrington Redistribution Wash
      in Washout may give additional information.

PMID- 22395669
TI  - Wrinkle-assisted linear assembly of hard-core/soft-shell particles: impact of the
      soft shell on the local structure.
AB  - This article addresses wrinkle assisted assembly of core-shell particles with
      hard cores and soft poly-(N-isopropylacrylamide) shells. As core materials we
      chose silica as well as silver nanoparticles. The assembled structures show that
      the soft shells act as a separator between the inorganic cores. Anisotropic
      alignment is found on two length scales, macroscopically guided through the
      wrinkle structure and locally due to deformation of the polymer shell leading to
      smaller inter-core separations as compared to assembly on flat substrates without
      confinement. The structures were analysed by means of scanning electron
      microscopy. Radial distribution functions are shown, clearly highlighting the
      impact of confinement on nearest neighbour distances and symmetry. The observed
      ordering is directly compared to Monte-Carlo simulations for hard-core/soft-shell
      particles, showing that the observed symmetries are a consequence of the soft
      interaction potential and differ qualitatively from a hard-sphere situation. For
      the silver-poly-(N-isopropylacrylamide) particles, we show UV-vis absorbance
      measurements revealing optical anisotropy of the generated structures due to
      plasmon coupling. Furthermore, the high degree of order of the assembled
      structures on macroscopic areas is demonstrated by laser diffraction effects.

PMID- 22395668
TI  - Effects of competition on hospital quality: an examination using hospital
      administrative data.
AB  - This paper investigates the effects of competition on hospital quality using
      hospital administration data from the State of Victoria, Australia. Hospital
      quality is measured by 30-day mortality rates and 30-day unplanned readmission
      rates. Competition is measured by Herfindahl-Hirschman index and the numbers of
      competing public and private hospitals. The paper finds that hospitals facing
      higher competition have lower unplanned admission rates. However, competition is
      related negatively to hospital quality when measured by mortality, albeit the
      effects are weak and barely statistically significant. The paper also finds that
      the positive effect of competition on quality as measured by unplanned
      readmission differs greatly depending on whether the hospital is publicly or
      privately owned.

PMID- 22395670
TI  - Low-frequency nevirapine resistance at multiple sites may predict treatment
      failure in infants on nevirapine-based treatment.
AB  - BACKGROUND: Resistance commonly arises in infants exposed to single-dose
      nevirapine (sdNVP) for prevention of mother to child transmission. Although K103N
      and Y181C are common following sdNVP, multiple other mutations also confer NVP
      resistance. It remains unclear whether specific NVP resistance mutations or
      combinations of mutations predict virologic failure in infants when present at
      low frequencies before NVP-based treatment. METHODS: Twenty sdNVP-exposed infants
      who were subsequently treated with NVP-based highly active antiretroviral therapy
      were examined. Pretreatment plasma samples were tested for the presence of NVP
      resistance mutations by allele-specific polymerase chain reaction for K103N and
      Y181C and ultradeep pyrosequencing (UDPS) for all primary NVP mutations. Viral
      levels were determined every 3 months for up to 24 months on NVP-highly active
      antiretroviral therapy. Cox proportional hazard models were used to determine
      correlates of viral failure. RESULTS: The NVP resistance mutations K103N or Y181C
      were detected in pretreatment plasma samples in 6 infants by allele-specific
      polymerase chain reaction. NVP resistance at these or other sites was detectable
      by UDPS in 10 of 20 infants tested. Virologic failure occurred in 50% of infants
      with any NVP resistance mutations detected, whereas only 20% of infants without
      resistance experienced viral failure, but the difference was not significant (P =
      0.19). An increase in the number of NVP resistance mutations detectable by UDPS
      in an infant was significantly associated with an increased risk of virologic
      failure [HR = 1.79 (95% confidence interval: 1.07 to 2.99), P = 0.027].
      CONCLUSIONS: Low frequencies of multiple NVP resistance mutations, in addition to
      K103N and Y181C, present in infants before NVP-based treatment may predict
      treatment outcome.

PMID- 22395671
TI  - Integration of HIV and TB services results in improved TB treatment outcomes and
      earlier prioritized ART initiation in a large urban HIV clinic in Uganda.
AB  - BACKGROUND: The World Health Organization recommends that treatment of
      tuberculosis (TB) in HIV-infected patients should be integrated with HIV care. In
      December 2008, a separate outdoor-integrated TB/HIV clinic was instituted for
      attendees of a large urban HIV clinic in Uganda. We sought to evaluate associated
      TB and HIV treatment outcomes. METHODS: Routinely collected clinical, pharmacy,
      and laboratory data were merged with TB clinic data for patients initiating TB
      treatment in 2009 and with TB register data for patients in 2007. TB treatment
      outcomes and (timing of) antiretroviral therapy (ART) initiation in ART-naive
      patients [overall and stratified by CD4+ T cell (CD4) count] in 2007 and 2009
      were compared. Nosocomial transmission rates could not be assessed. RESULTS:
      Three hundred forty-six patients were initiated on TB treatment in 2007 and 366
      in 2009. Median CD4 counts at TB diagnosis did not differ. TB treatment cure or
      completion increased from 62% to 68%, death or default decreased from 33% to 25%
      (P < 0.001). Fewer ART-naive TB patients were initiated on ART in 2009 versus
      2007 (57% and 66%, P = 0.031), but this decrease was only in patients with CD4
      counts >250 cells per cubic millimeter (19% vs. 48%, P = 0.003). More patients
      were started on ART during TB treatment (94% vs. 78%, P < 0.001). Moreover, the
      majority were now initiated during intensive phase (60% vs. 23%, P < 0.001).
      CONCLUSIONS: Integration of TB and HIV care has led to improved TB treatment
      outcomes and earlier, prioritized ART initiation. This supports rollout of a
      fully integrated TB/HIV service delivery model throughout high-prevalence TB and
      HIV settings.

PMID- 22395672
TI  - A randomized controlled trial of highly active antiretroviral therapy versus
      highly active antiretroviral therapy and chemotherapy in therapy-naive patients
      with HIV-associated Kaposi sarcoma in South Africa.
AB  - BACKGROUND: The optimal approach to HIV-associated Kaposi sarcoma (HIV-KS) in sub
      Saharan Africa is unknown. With large-scale rollout of highly active
      antiretroviral therapy (HAART) in South Africa, we hypothesized that survival in
      HIV-KS would improve and administration of chemotherapy in addition to HAART
      would be feasible and improve KS-specific outcomes. METHODS: We conducted a
      randomized, controlled, open-label trial with intention-to-treat analysis.
      Treatment-naive patients from King Edward VIII Hospital, Durban, South Africa, a
      public-sector tertiary referral center, with HIV-KS, but no symptomatic visceral
      disease or fungating lesions requiring urgent chemotherapy, were randomized to
      HAART alone or HAART and chemotherapy (CXT). HAART arm received stavudine,
      lamivudine, and nevirapine (Triomune; CXT arm received Triomune plus bleomycin,
      doxorubicin, and vincristine every 3 weeks. When bleomycin, doxorubicin, and
      vincristine were not available, oral etoposide (50-100 mg for 1-21 days of a 28
      day cycle) was substituted. Primary outcome was overall KS response using AIDS
      Clinical Trial Group criteria 12 months after HAART initiation. Secondary
      comparisons included time to response, progression-free survival, overall
      survival, adverse events, HIV control, CD4 reconstitution, adherence, and quality
      of life. RESULTS: Fifty-nine subjects were randomized to HAART and 53 to CXT; 12
      month overall KS response was 39% in the HAART arm and 66% in the CXT arm
      (difference, 27%; 95% confidence interval, 9%-43%; P = 0.005). At 12 months, 77%
      were alive (no survival difference between arms; P = 0.49), 82% had HIV viral
      load <50 copies per milliliter without difference between the arms (P = 0.47);
      CD4 counts and quality-of-life measures improved in all patients. CONCLUSIONS:
      HAART with chemotherapy produced higher overall KS response over 12 months,
      whereas HAART alone provided similar improvement in survival and select measures
      of morbidity. In Africa, with high prevalence of HIV and human herpes virus-8 and
      limited resources, HAART alone provides important benefit in patients with HIV
      KS.

PMID- 22395675
TI  - The persistence of polio.

PMID- 22395674
TI  - T-maze forced alternation and left-right discrimination tasks for assessing
      working and reference memory in mice.
AB  - Forced alternation and left-right discrimination tasks using the T-maze have been
      widely used to assess working and reference memory, respectively, in rodents. In
      our laboratory, we evaluated the two types of memory in more than 30 strains of
      genetically engineered mice using the automated version of this apparatus. Here,
      we present the modified T-maze apparatus operated by a computer with a video
      tracking system and our protocols in a movie format. The T-maze apparatus
      consists of runways partitioned off by sliding doors that can automatically open
      downward, each with a start box, a T-shaped alley, two boxes with automatic
      pellet dispensers at one side of the box, and two L-shaped alleys. Each L-shaped
      alley is connected to the start box so that mice can return to the start box,
      which excludes the effects of experimenter handling on mouse behavior. This
      apparatus also has an advantage that in vivo microdialysis, in vivo
      electrophysiology, and optogenetics techniques can be performed during T-maze
      performance because the doors are designed to go down into the floor. In this
      movie article, we describe T-maze tasks using the automated apparatus and the T
      maze performance of alpha-CaMKII+/- mice, which are reported to show working
      memory deficits in the eight-arm radial maze task. Our data indicated that alpha
      CaMKII+/- mice showed a working memory deficit, but no impairment of reference
      memory, and are consistent with previous findings using the eight-arm radial maze
      task, which supports the validity of our protocol. In addition, our data indicate
      that mutants tended to exhibit reversal learning deficits, suggesting that alpha
      CaMKII deficiency causes reduced behavioral flexibility. Thus, the T-maze test
      using the modified automatic apparatus is useful for assessing working and
      reference memory and behavioral flexibility in mice.

PMID- 22395676
TI  - NIH accused of being overly literal on stem cell approvals.

PMID- 22395677
TI  - Genomics contest underscores challenges of personalized medicine.

PMID- 22395673
TI  - Mechanical circulatory support: devices, outcomes and complications.
AB  - Systolic heart failure is a problem of substantial magnitude worldwide. Over the
      last 25 years great progress has been made in the medical management of heart
      failure with the recognition of the benefits of beta-adrenergic blockade,
      modulation of the renin-angiotensin and mineralocorticoid axes and judicious
      diuretic therapy. In addition, cardiac resynchronization therapy and prophylactic
      implantation of cardiac defibrillators have been responsible for measurable
      benefits in terms of functional status and dysrhythmia-related mortality,
      respectively. Unfortunately, progressive cardiac dysfunction often results in
      activity limitation, symptoms at rest, hospital admission, end-organ dysfunction
      and death despite maximal implementation of standard therapies. Heart
      transplantation has been a dramatic and effective therapy for end-stage heart
      failure, but it remains limited by a shortage of donor organs, strict criteria
      defining acceptable recipients and often unsatisfactory long-term success.
      Mechanical alternatives to support the failing circulation have been sought for
      the last 50 years. The history of device development has been marked in general
      by the slow progress achieved by a few dedicated and persevering pioneers. In the
      past decade, however, evolving technology has dramatically changed the field and
      broadened the options for the treatment of advanced heart failure. This review
      will detail the important milestones and the current state of the art, with an
      emphasis on implantable devices for intermediate to long term support.

PMID- 22395678
TI  - Trial designs for vaccines adapt to the times.

PMID- 22395679
TI  - Limb-saving medicines sought to prevent amputations.

PMID- 22395680
TI  - Korea okays stem cell therapies despite limited peer-reviewed data.

PMID- 22395682
TI  - Small biotechs raring to cash in on the orphan disease market.

PMID- 22395683
TI  - New blood-boosting drugs aim to staunch renal anemia.

PMID- 22395685
TI  - Indian TB cases highlight need for drug-resistance tests.

PMID- 22395686
TI  - Nodding syndrome leaves baffled scientists shaking their heads.

PMID- 22395687
TI  - Straight talk with... Robert Beall. Interviewed by Elie Dolgin.

PMID- 22395690
TI  - Diagnosis by default.

PMID- 22395691
TI  - Public-private partnerships need honest brokering.

PMID- 22395693
TI  - Chemotherapy response of spontaneous mammary tumors is independent of the
      adaptive immune system.

PMID- 22395694
TI  - HIV-1 Env antibodies: are we in a bind or going blind?

PMID- 22395697
TI  - Chipping away at the lung cancer genome.

PMID- 22395698
TI  - The AKTion in non-canonical insulin signaling.

PMID- 22395699
TI  - The quest for human ovarian stem cells.

PMID- 22395700
TI  - Quantifying the activity of anti-HIV treatment in silico.

PMID- 22395701
TI  - At the heart of the benefits of bariatric surgery.

PMID- 22395710
TI  - Coherent manipulation of free amino acids fluorescence.
AB  - Coherent manipulation of molecular wavepackets in biomolecules might contribute
      to the quest towards label-free cellular imaging and protein identification. We
      report the use of optimally tailored UV laser pulses in pump-probe depletion
      experiments that selectively enhance or decrease fluorescence between two
      aromatic amino acids: tryptophan (Trp) and tyrosine (Tyr). Selective fluorescence
      modulation is achieved with a contrast of ~35%. A neat modification of the time
      dependent fluorescence depletion signal of Trp is observed, while the Tyr
      transient trace remains unchanged. The mechanism invoked for explaining the
      change of the depletion of Trp is a less efficient coupling between the
      fluorescing state and the higher non-radiative excited states by the optimally
      shaped pulse, than by the reference pulse.

PMID- 22395711
TI  - Primary osteosarcoma of the ureter.
AB  - Primary osteosarcoma of the ureter is an extremely rare disease. Herein, the
      authors report a case of extraosseous osteosarcoma arising in the ureter of a 64
      year-old woman. Ureteroscopy showed a papillary mass that protruded into and
      almost completely occluded the lumen. The tumor was successfully removed, and
      pathologic analysis identified mitotically active spindle cells and focal areas
      that contained osteoid. The tumor cells were strongly positive for vimentin but
      negative for cytokeratin (CK), CK7, CK20 and leukocyte-common antigen, supporting
      a diagnosis of high-grade extraosseous osteosarcoma of the ureter. The patient
      recovered well from surgery and exhibited no evidence of local recurrence or
      distant metastasis 6 months after the surgery. To the best of our knowledge, this
      is only the third reported case of primary osteosarcoma of the ureter.

PMID- 22395712
TI  - Pulmonary hernia.

PMID- 22395709
TI  - The cellular and signaling networks linking the immune system and metabolism in
      disease.
AB  - It is now recognized that obesity is driving the type 2 diabetes epidemic in
      Western countries. Obesity-associated chronic tissue inflammation is a key
      contributing factor to type 2 diabetes and cardiovascular disease, and a number
      of studies have clearly demonstrated that the immune system and metabolism are
      highly integrated. Recent advances in deciphering the various cellular and
      signaling networks that participate in linking the immune and metabolic systems
      together have contributed to understanding of the pathogenesis of metabolic
      diseases and may also inform new therapeutic strategies based on
      immunomodulation. Here we discuss how these various networks underlie the
      etiology of the inflammatory component of insulin resistance, with a particular
      focus on the central roles of macrophages in adipose tissue and liver.

PMID- 22395713
TI  - Prevalence and characteristics of herpes simplex virus type-2 coinfection in
      veterans with hepatitis C.
AB  - INTRODUCTION: Epidemiologic links between herpes simplex virus type-2 (HSV-2) and
      hepatitis C virus (HCV) exist but are poorly characterized. Seroprevalence
      studies of HSV-2 in veteran populations with chronic HCV infection are lacking.
      METHODS: The authors reviewed the medical histories and results of the
      HerpeSelect IgG (Focus Diagnostics, Cypress, CA) of 244 HCV-infected male
      veterans engaged in care. All patients were human immunodeficiency virus negative
      and >99% defined themselves as heterosexual. RESULTS: Using the manufacturer's
      recommended cutoff for positive results (>1.1), 51.5% of HCV-infected veterans
      were seropositive for HSV-2. When increasing the cutoff to >3.5, 38.7% of persons
      were seropositive for HSV-2. Reports of previous diagnosis with genital ulcer
      disease (9/213; 4.3%) or genital herpes (4/213; 1.9%) were rare. CONCLUSIONS: HSV
      2 infection commonly occurred in the study sample of HCV-infected veterans but
      was infrequently recognized. Future studies should optimize the use of type
      specific serologic screening tests in HCV-infected persons. The high prevalence
      of HSV-2 in this population merits further investigation into any potential
      biologic interactions between these common viral infections.

PMID- 22395714
TI  - Effects of combined glucose and fat load on endothelium-dependent brachial artery
      vasodilatation in hypertensive patients.
AB  - INTRODUCTION: This study investigated the effects of combined glucose and fat
      load on glucose and lipid metabolism, as well as on vascular endothelial
      function, in hypertensive patients. METHODS AND RESULTS: A total of 98
      hypertensive patients were randomly divided into 3 groups that received an oral
      fat tolerance test (OFTT), an oral glucose tolerance test (OGTT) or a combined
      oral glucose and fat tolerance test (OGFTT). Endothelium-dependent flow-mediated
      brachial artery dilation (FMD) was measured by vascular ultrasound and was used
      as an indicator of vascular endothelial function. There were no significant
      differences in demographics or clinical characteristics among the 3 groups before
      the study. Immediately after the OGFTT, the serum triglyceride levels and the
      area under the curve for serum glucose in the OGFTT group were not significantly
      different from those in the other 2 groups. However, the 1-hour FMD in the OGFTT
      group was significantly reduced compared with that of the OGTT group (5.45 +/-
      0.75 versus 9.46 +/- 1.32, P < 0.05), and the 4-hour FMD in the OGFTT group was
      also significantly reduced compared with the OFTT group (8.56 +/- 1.09 versus
      9.76 +/- 2.00, P < 0.05). CONCLUSION: A combined glucose and fat load has a
      cumulative effect on vascular endothelial dysfunction in hypertensive patients.

PMID- 22395715
TI  - Contralateral prophylactic mastectomy:  clinical and pathological features from a
      prospective database.
AB  - INTRODUCTION: In keeping with recently documented national trends, a significant
      and increasing number of patients will have chosen contralateral prophylactic
      mastectomy (CPM) based on personal preference, without traditional clinical or
      pathological indication. METHODS: Women who underwent CPM at the University of
      Louisville from 2003 to 2009 were selected for this study. Descriptive factors
      were evaluated such as age, race, family history of breast cancer, laterality,
      hormone receptor status, stage, grade and histology of the index breast lesion.
      Statistical analysis was used to compute predictive factors for occult
      contralateral pathology. RESULTS: A total of 107 patients underwent CPM and had
      adequate medical information to be included in this study. The median age was 48
      years, with 88% being white and 12% being African American. Seventy-six percent
      of the index breast cancers were infiltrating ductal carcinoma and 12% were
      infiltrating lobular carcinoma. Five "significant" occult pathologies were found
      in the prophylactically removed breast. Two of the lesions were ductal carcinoma
      in situ, 2 were lobular carcinoma in situ and 1 was an invasive mucinous
      carcinoma. On bivariate analysis, there were no factors identified predictive for
      occult contralateral pathology. CONCLUSIONS: In line with previously reported
      data, we noted that fewer than 5% of patients who underwent CPM had pathology in
      the contralateral breast. We were unable to correlate any clinical or
      pathological characteristics in women who presented with contralateral breast
      cancer. This study raises serious questions regarding the clinical utility of CPM
      in detecting synchronous clinically and radiographically occult contralateral
      primaries.

PMID- 22395716
TI  - Executive summary: advances in fetal and neonatal imaging.

PMID- 22395717
TI  - Imaging clues in the prenatal diagnosis of syndromes and aneuploidy.
AB  - Advances in fetal sonography and MRI have increased both the range and diagnostic
      accuracy of detectable fetal anomalies, with many anomalies detectable earlier in
      pregnancy. The presence of structural anomalies greatly raises the risk that the
      fetus has a syndrome or abnormal karyotype. In addition, new techniques in
      maternal serum screening have greatly increased the ability to identify pregnant
      patients at risk for anomalies and syndromes. This paper reviews maternal first-
      and second-trimester serum screening and imaging and covers many of the most
      common fetal karyotypic and structural anomalies.

PMID- 22395718
TI  - Novel applications of quantitative MRI for the fetal brain.
AB  - The advent of ultrafast MRI acquisitions is offering vital insights into the
      critical maturational events that occur throughout pregnancy. Concurrent with the
      ongoing enhancement of ultrafast imaging has been the development of innovative
      image-processing techniques that are enabling us to capture and quantify the
      exuberant growth, and organizational and remodeling processes that occur during
      fetal brain development. This paper provides an overview of the role of advanced
      neuroimaging techniques to study in vivo brain maturation and explores the
      application of a range of new quantitative imaging biomarkers that can be used
      clinically to monitor high-risk pregnancies.

PMID- 22395720
TI  - Imaging of fetal chest masses.
AB  - Prenatal imaging with high-resolution US and rapid acquisition MRI plays a key
      role in the accurate diagnosis of congenital chest masses. Imaging has enhanced
      our understanding of the natural history of fetal lung masses, allowing for
      accurate prediction of outcome, parental counseling, and planning of pregnancy
      and newborn management. This paper will focus on congenital bronchopulmonary
      malformations, which account for the vast majority of primary lung masses in the
      fetus. In addition, anomalies that mimic masses and less common causes of lung
      masses will be discussed.

PMID- 22395721
TI  - Update on the diagnosis and management of bronchopulmonary dysplasia/chronic lung
      disease of infancy: what the radiologist should know.
AB  - Pediatric radiologists are frequently called upon to render interpretations of
      chest radiographs performed on premature infants with chronic respiratory
      problems. After the acute phase of surfactant deficiency (respiratory distress
      syndrome), infants with persistent respiratory problems are loosely categorized
      by clinicians as evolving toward a broad, rather vague entity called
      bronchopulmonary dysplasia (BPD) or chronic lung disease (CLD). This review aims
      to update the radiologist on how the characteristics of the disease have shifted
      and how management, diagnosis and pathology have changed since the disorder was
      first described more than 40 years ago. The radiologist armed with this
      information might be better prepared to provide insightful reporting and address
      the needs of the neonatologist.

PMID- 22395719
TI  - Neuroimaging biomarkers of preterm brain injury: toward developing the preterm
      connectome.
AB  - For typically developing infants, the last trimester of fetal development
      extending into the first post-natal months is a period of rapid brain
      development. Infants who are born premature face significant risk of brain injury
      (e.g., intraventricular or germinal matrix hemorrhage and periventricular
      leukomalacia) from complications in the perinatal period and also potential long
      term neurodevelopmental disabilities because these early injuries can interrupt
      normal brain maturation. Neuroimaging has played an important role in the
      diagnosis and management of the preterm infant. Both cranial US and conventional
      MRI techniques are useful in diagnostic and prognostic evaluation of preterm
      brain development and injury. Cranial US is highly sensitive for intraventricular
      hemorrhage (IVH) and provides prognostic information regarding cerebral palsy.
      Data are limited regarding the utility of MRI as a routine screening instrument
      for brain injury for all preterm infants. However, MRI might provide diagnostic
      or prognostic information regarding PVL and other types of preterm brain injury
      in the setting of specific clinical indications and risk factors. Further
      development of advanced MR techniques like volumetric MR imaging, diffusion
      tensor imaging, metabolic imaging (MR spectroscopy) and functional connectivity
      are necessary to provide additional insight into the molecular, cellular and
      systems processes that underlie brain development and outcome in the preterm
      infant. The adult concept of the "connectome" is also relevant in understanding
      brain networks that underlie the preterm brain. Knowledge of the preterm
      connectome will provide a framework for understanding preterm brain function and
      dysfunction, and potentially even a roadmap for brain plasticity. By combining
      conventional imaging techniques with more advanced techniques, neuroimaging
      findings will likely be used not only as diagnostic and prognostic tools, but
      also as biomarkers for long-term neurodevelopmental outcomes, instruments to
      assess the efficacy of neuroprotective agents and maneuvers in the NICU, and as
      screening instruments to appropriately select infants for longitudinal
      developmental interventions.

PMID- 22395722
TI  - Fetal bowel anomalies--US and MR assessment.
AB  - The technical quality of prenatal US and fetal MRI has significantly improved
      during the last decade and allows an accurate diagnosis of bowel pathology
      prenatally. Accurate diagnosis of bowel pathology in utero is important for
      parental counseling and postnatal management. It is essential to recognize the US
      presentation of bowel pathology in the fetus in order to refer the patient for
      further evaluation or follow-up. Fetal MRI has been shown to offer some
      advantages over US for specific bowel abnormalities. In this paper, we review the
      normal appearance of the fetal bowel on US and MRI as well as the typical
      presentations of bowel pathologies. We discuss more specifically the importance
      of recognizing on fetal MRI the abnormalities of size and T1-weighted signal of
      the meconium-filled distal bowel.

PMID- 22395723
TI  - US assessment of neonatal bowel (necrotizing enterocolitis excluded).
AB  - US plays a main role in evaluating neonatal gastrointestinal disorders. The
      authors describe the US appearance of normal neonatal bowel, midgut volvulus,
      small bowel atresia, meconium ileus, meconium peritonitis, different meconium
      plug syndromes, Hirschsprung disease, intestinal duplication cysts, some other
      abdominal cysts, some intraperitoneal infections, excluding necrotizing
      enterocolitis, and anorectal anomalies. The use of sonography in the imaging
      diagnostic strategies of these congenital and acquired anomalies is emphasized.

PMID- 22395724
TI  - Fetal genitourinary imaging.
AB  - The fetal urinary tract is routinely evaluated sonographically beginning in the
      first trimester with documentation of fetal bladder visualization. Fetal MR might
      be indicated to further clarify abnormalities found sonographically. The primary
      imaging modality for evaluation of the fetal kidney is US, which plays an
      important role in the detection of collecting system dilatation and parenchymal
      diseases that influence counseling and postnatal care. A commonly seen birth
      defect affecting the fetal kidney is pyelectasis. The significance of this
      finding has been extensively evaluated by a number of fetal imaging centers and
      will be presented in this review. Further topics of interest within the fetal
      genitourinary system include fetal renal parenchymal disorders and fetal bladder
      abnormalities. Characteristic imaging features, as well as developmental
      pathology and differential considerations, are discussed here.

PMID- 22395725
TI  - Postnatal imaging of neonates with prenatally diagnosed genitourinary
      abnormalities: a practical approach.
AB  - The advent of prenatal US and, more recently, fetal MRI has changed our pattern
      of referrals. In the current clinical algorithms, most neonates evaluated for
      genitourinary abnormalities are asymptomatic. These infants are referred for
      multidisciplinary consultation, imaging and surveillance. Evaluation of these
      children commences following pertinent review of available prenatal studies; this
      is appropriate, as in certain instances prenatally gathered information of
      potential prognostic significance can be inferred or can obviate the need for
      multiple examinations. US remains the first-line imaging modality for diagnosing
      urinary abnormalities in neonates and young infants, although it offers primarily
      morphological assessment. However, US coupled with MAG-3 scanning results in a
      powerful combination that provides anatomical and functional information.
      Recently, MRI and MR urography have been increasingly regarded as one-stop-shop
      examinations that can deliver both anatomical and functional information, and
      play an increasing role in the evaluation of ureteral ectopia and genital
      anomalies. Fluoroscopic examinations are reserved to exclude vesicoureteral
      reflux, to delineate urethral obstruction or to provide additional information to
      support a diagnosis. A practical approach to postnatal imaging of the neonate is
      discussed and the important genitourinary anomalies in this age group are
      presented and illustrated.

PMID- 22395726
TI  - Low-dose fetal CT for evaluation of severe congenital skeletal anomalies:
      preliminary experience.
AB  - Congenital skeletal abnormalities compose a heterogeneous and complex group of
      conditions that affect bone growth and development and result in various
      anomalies in shape and size of the skeleton. Prenatal sonographic diagnosis of
      these anomalies is challenging because of the relative rarity of each skeletal
      dysplasia, the multitude of differential diagnoses encountered when the bony
      abnormalities are identified, lack of precise molecular diagnosis and the fact
      that many of these disorders have overlapping features and marked phenotypic
      variability. The following review is a preliminary summary of our experience at
      the Children's Hospital of Philadelphia (CHOP) using low-dose fetal CT in the
      evaluation of severe fetal osseous abnormalities.

PMID- 22395727
TI  - Neonatal skeletal dysplasias.
AB  - Skeletal dysplasias are a large diverse group of disorders characterized by
      abnormal bone and cartilage growth. Approximately one-quarter of them are
      considered lethal in the perinatal period. This paper will review the components
      of the skeletal survey, the primary imaging tool for diagnosing dysplasias
      postnatally, emphasizing the use of an organized approach and appropriate
      descriptive terminology. Several illustrative cases of lethal and nonlethal
      dysplasias will be shown, with additional discussion of commonly associated
      genetic mutations and classification systems.

PMID- 22395728
TI  - Fetal and neonatal bone health: update on bone growth and manifestations in
      health and disease.
AB  - The neonatal period is classically described as the first 28 days of life, but
      owing to the fact that changes in skeletal tissue occur at a somewhat slower pace
      than those of other organ systems, events of the first few months are considered
      herein. Neonatal bone health is a problem of growing interest and concern because
      of the increasing recognition of its impact upon childhood, adolescent and even
      adult bone health. Osteoporosis in adulthood often has its roots in childhood and
      some forms may be prevented by proper attention to neonatal and childhood bone
      health. The premature infant likely suffers lifelong decreased bone mineral
      density as a result of its early birth and lack of adequate mineral stores that
      are typically present in full-term infants. Adequate embryogenesis, growth and
      development of the skeletal system are multifactorial and under the influence of
      a host of genes, growth factors and enzymes. The evaluation of skeletal
      dysplasias and their recognition are beyond the scope of this paper and will not
      be considered in this discussion. Here the focus will be on the adequacy of
      mineralization and metabolic aspects of the growth and development of the fetal
      and neonatal skeleton, the effect of birth, both preterm and term, maternal
      illness and health as well as infant diseases.

PMID- 22395729
TI  - Effect of ethanol extract of Trigonella foenum graecum (Fenugreek) seeds on
      Freund's adjuvant-induced arthritis in albino rats.
AB  - Trigonella foenum graecum is an Iranian medicinal plant used for the treatment of
      rheumatoid arthritis and inflammation. The present study was designed to
      investigate the beneficial outcome of the plant T. foenum graecum on adjuvant
      induced arthritis in albino rats. Ethanol extract of T. foenum graecum was tested
      against Freund's complete adjuvant-induced arthritis in rats. In the present
      study, paw volume was measured on the 4th, 8th, 14th and 21st day. On day 22,
      animals were anaesthetized, and blood samples were collected for the estimation
      of haemoglobin, white blood cells (WBC), differential white blood cells,
      erythrocyte sedimentation rate (ESR), red blood cells (RBC), interleukins (IL
      1alpha, IL-1beta, IL-2, IL-6) and tumour necrosis factor-alpha (TNF-alpha). The
      animals were sacrificed, and the cartilage tissue was isolated for estimation of
      lipid peroxidation (LPO), superoxide dismutase (SOD) and glutathione (GSH).
      Administration with both doses of T. foenum graecum (200 and 400 mg/kg)
      significantly (P < 0.05) decreased the paw oedema and restored body weight. T.
      foenum graecum significantly (P < 0.05) reduced the differential WBC count, ESR
      and WBC (5.833 +/- 0.703, 6.989 +/- 58.5) content and also showed significant (P
      < 0.05) increase in RBC and Hb (4.783 +/- 0.46, 15.46 +/- 0.158) content. T.
      foenum graecum significantly (P < 0.05) decreased the IL-1alpha, IL-1beta, IL-2,
      IL-6 and TNF-alpha levels. It also significantly decreased the levels of LPO and
      increased the SOD and GSH levels in cartilage tissue. In this study, T. foenum
      graecum 400-mg/kg dose showed more prominent results compared to the 200-mg/kg
      dose of T. foenum graecum. The results obtained in this study suggest that anti
      inflammatory and antioxidant activities of T. foenum graecum may be the possible
      reason behind the observed anti-arthritic activity.

PMID- 22395730
TI  - Cocaine self-administration produces pharmacodynamic tolerance: differential
      effects on the potency of dopamine transporter blockers, releasers, and
      methylphenidate.
AB  - The dopamine transporter (DAT) is the primary site of action for psychostimulant
      drugs such as cocaine, methylphenidate, and amphetamine. Our previous work
      demonstrated a reduced ability of cocaine to inhibit the DAT following high-dose
      cocaine self-administration (SA), corresponding to a reduced ability of cocaine
      to increase extracellular dopamine. However, this effect had only been
      demonstrated for cocaine. Thus, the current investigations sought to understand
      the extent to which cocaine SA (1.5 mg/kg/inf * 40 inf/day * 5 days) altered the
      ability of different dopamine uptake blockers and releasers to inhibit dopamine
      uptake, measured using fast-scan cyclic voltammetry in rat brain slices. We
      demonstrated that, similar to cocaine, the DAT blockers nomifensine and bupropion
      were less effective at inhibiting dopamine uptake following cocaine SA. The
      potencies of amphetamine-like dopamine releasers such as 3,4
      methylenedioxymethamphetamine, methamphetamine, amphetamine, and phentermine, as
      well as a non-amphetamine releaser, 4-benzylpiperidine, were all unaffected.
      Finally, methylphenidate, which blocks dopamine uptake like cocaine while being
      structurally similar to amphetamine, shared characteristics of both, resembling
      an uptake blocker at low concentrations and a releaser at high concentrations.
      Combined, these experiments demonstrate that after high-dose cocaine SA, there is
      cross-tolerance of the DAT to other uptake blockers, but not releasers. The
      reduced ability of psychostimulants to inhibit dopamine uptake following cocaine
      SA appears to be contingent upon their functional interaction with the DAT as a
      pure blocker or releaser rather than their structural similarity to cocaine.
      Further, methylphenidate's interaction with the DAT is unique and concentration
      dependent.

PMID- 22395731
TI  - Dopamine modulates reward system activity during subconscious processing of
      sexual stimuli.
AB  - Dopaminergic medication influences conscious processing of rewarding stimuli, and
      is associated with impulsive-compulsive behaviors, such as hypersexuality.
      Previous studies have shown that subconscious subliminal presentation of sexual
      stimuli activates brain areas known to be part of the 'reward system'. In this
      study, it was hypothesized that dopamine modulates activation in key areas of the
      reward system, such as the nucleus accumbens, during subconscious processing of
      sexual stimuli. Young healthy males (n=53) were randomly assigned to two
      experimental groups or a control group, and were administered a dopamine
      antagonist (haloperidol), a dopamine agonist (levodopa), or placebo. Brain
      activation was assessed during a backward-masking task with subliminally
      presented sexual stimuli. Results showed that levodopa significantly enhanced the
      activation in the nucleus accumbens and dorsal anterior cingulate when subliminal
      sexual stimuli were shown, whereas haloperidol decreased activations in those
      areas. Dopamine thus enhances activations in regions thought to regulate
      'wanting' in response to potentially rewarding sexual stimuli that are not
      consciously perceived. This running start of the reward system might explain the
      pull of rewards in individuals with compulsive reward-seeking behaviors such as
      hypersexuality and patients who receive dopaminergic medication.

PMID- 22395732
TI  - Olanzapine, but not fluoxetine, treatment increases survival in activity-based
      anorexia in mice.
AB  - Anorexia nervosa (AN) is an eating disorder characterized by extreme hypophagia,
      hyperactivity, and fear of weight gain. No approved pharmacological treatments
      exist for AN despite high mortality rates. The activity-based anorexia (ABA)
      phenomenon models aspects of AN in rodents, including progressive weight loss,
      reduced food intake, and hyperactivity. First, we optimized the ABA paradigm for
      mice. We compared mouse strains (Balb/cJ, A/J) for susceptibility with ABA, and
      evaluated the effects of different food access durations (2, 4, 6, 8, and 10 h)
      on ABA parameters. Balb/cJ mice exhibited significantly shorter survival time
      (days until 25% bodyweight loss) in the ABA paradigm compared with A/J mice.
      Furthermore, 6 h of food access reduced survival in mice housed with wheels
      without reducing survival in mice housed without wheels. We then evaluated the
      effects of chronic treatment with fluoxetine (4 weeks) or subchronic treatment
      with olanzapine (OLZ) (1 week) on ABA in BALB/cJ mice. OLZ (12 mg/kg/day)
      significantly increased survival and reduced food anticipatory activity (FAA).
      However, OLZ did not alter food intake or running wheel activity during ad-lib
      feeding (baseline) or restriction conditions, or in mice housed without wheels.
      Fluoxetine (18 mg/kg/day) increased food intake and reduced FAA, but did not
      alter survival. Here, we report for the first time that OLZ, but not fluoxetine,
      reduces ABA in mice. Our findings indicate further need for clinical
      investigations into the effects of OLZ, but not selective serotonin reuptake
      inhibitors, on core features of AN.

PMID- 22395734
TI  - Prediction of 3-hydroxypyridin-4-one (HPO) hydroxyl pKa values.
AB  - As an aid in optimising the design of 3-hydroxypyridin-4-ones (HPOs) intended for
      use as therapeutic Fe(3+) chelating agents, various quantum mechanical (QM) and
      semi-empirical (QSAR) methods have been explored for predicting the pK(a) values
      of the hydroxyl groups in these compounds. Using a training set of 15 HPOs with
      known hydroxyl pK(a) values, reliable predictions are shown to be obtained with
      QM calculations using the B3LYP/6-31+G(d)/CPCM model chemistry (with Pauling
      radii, and water as solvent). With this methodology, the observed hydroxyl pK(a)
      values for the training set compound are closely matched by the predicted pK(a)
      values, with the correlation between the observed and predicted values giving
      r(2) = 0.98. Predictions subsequently made by this method for a test set of 48
      HPOs of known hydroxyl pK(a) values (11 of which were determined experimentally
      in this study), gave predicted pK(a) values accurate to within +/-0.2 log units.
      In order to further investigate the predictive power of the method, two novel
      HPOs were synthesised and their hydroxyl pK(a) values were determined
      experimentally. Comparison of these predicted pK(a) values against the measured
      values gave absolute deviations of 0.13 (10.18 vs. 10.31) and 0.43 (5.58 vs.
      5.15).

PMID- 22395733
TI  - A single administration of low-dose varenicline saturates alpha4beta2* nicotinic
      acetylcholine receptors in the human brain.
AB  - The primary objective of this project was to determine the alpha4beta2(*)
      nicotinic acetylcholine receptor (nAChR) occupancy in human brain of a single low
      dose of varenicline (0.5 mg), and to explore the relationship between receptor
      occupancy by varenicline and tobacco withdrawal symptoms ((*)denoting other
      putative nAChR subunits). Otherwise healthy smokers (n=9) underwent two positron
      emission tomography (PET) sessions with the selective alpha4beta2(*) radioligand
      2-FA. For the PET sessions, participants received either a low dose of
      varenicline (0.5 mg) or matching placebo pill (double-blind, random order) before
      imaging. For both sessions, participants received bolus plus continuous infusions
      of 2-FA, were scanned for 1 h after allowing the radiotracer to reach a steady
      state, smoked to satiety, and were scanned for 2 more hours. We estimated the
      fractional receptor occupancy by a single dose of varenicline (0.5 mg) and the
      corresponding varenicline dissociation constant (K(V)), along with the effect of
      low-dose varenicline, pill placebo, and smoking-to-satiety on withdrawal rating
      scales. The data are compatible with 100% occupancy of alpha4beta2(*) nAChRs by a
      single dose of varenicline, with a 90% lower confidence limit of 89% occupancy
      for the thalamus and brainstem. The corresponding 90% upper limit on effective
      K(V) with respect to plasma varenicline was 0.49 nM. Smoking to satiety, but not
      low-dose varenicline, significantly reduced withdrawal symptoms. Our findings
      demonstrate that low-dose varenicline results in saturation of alpha4beta2(*)
      nAChRs in the thalamus and brainstem without reducing withdrawal symptoms.

PMID- 22395736
TI  - Consenting to donation: an examination of current practices in informed consent
      for tissue donation in the US.
AB  - Informed consent is the primary moral principle guiding the donation of human
      tissue for transplant purposes. When patients' donation wishes are not known,
      family members making the decision about tissue donation should be provided with
      requisite information needed to make informed donation decisions. Using a unique
      dataset of 1,016 audiotaped requests for tissue obtained from 15 US tissue
      banking organizations, we examined whether the information provided to families
      considering tissue donation met current standards for informed consent. The
      results indicated that many elements of informed consent were missing from the
      donation discussions, including the timeframe for procurement, autopsy issues,
      the involvement of both for-profit and nonprofit organizations, and the
      processing, storage and distribution of donated tissue. A multiple linear
      regression analysis also revealed that nonwhites and family members of increased
      age received less information regarding tissue donation than did younger, white
      decision makers. Recommendations for improving the practice of obtaining consent
      to tissue donation are provided.

PMID- 22395735
TI  - Docosahexaenoic acid sensitizes colon cancer cells to sulindac sulfide-induced
      apoptosis.
AB  - Sulindac analogs represent one of the most efficacious groups of NSAIDs reducing
      the risk of colon cancer. Recent studies have shown that sulindac sulfide, a
      sulindac analog effective at lower doses compared to its parent compound,
      triggers the death receptor (DR)5-dependent extrinsic apoptotic pathway.
      Induction of apoptosis via activation of the DR-mediated pathway would be an
      ideal therapeutic strategy to eliminate cancer cells. In this study, we
      investigated the possibility that colon cancer cells are sensitized to sulindac
      sulfide-induced apoptosis by docosahexaenoic acid (DHA), via activation of the
      DR/extrinsic apoptotic pathway. Our data demonstrated that DHA combination
      sensitized colon cancer cells to sulindac sulfide-induced apoptosis, leading to
      enhanced growth suppression of human colon cancer xenografts. The combination
      effect was primarily attributed to increased cleavage of poly(ADP-ribose)
      polymerase (PARP) and caspase-8 activation. Moreover, pretreatment with z-IETD
      FMK (caspase-8 inhibitor) or stable expression of dominant negative caspase-8
      genes blocked DHA/sulindac sulfide cotreatment-induced apoptosis. In view of the
      finding that DR5 silencing abrogated the combination-stimulated apoptosis, we
      propose that apoptotic synergy induced by sulindac sulfide plus DHA is mediated
      via DR5. Our findings collectively support the utility of a combination of
      sulindac sulfide and DHA in the effective prevention and treatment of colon
      cancer.

PMID- 22395737
TI  - Adipose tissue can be generated in vitro by using adipocytes from human fat
      tissue mesenchymal stem cells seeded and cultured on fibrin gel sheet.
AB  - The current study has developed an innovative procedure to generate ex novo fat
      tissue by culturing adipocytes from human fat tissue mesenchymal stem cells
      (hFTMSCs) on fibrin gel sheet towards applications in medicine and cosmetology.
      Fibrin gel has been obtained by combining two components fibrinogen and thrombin
      collected by human peripheral blood. By this procedure it was possible to
      generate blocks of fibrin gel containing adipocytes within the gel that show
      similar features and consistency to human fat tissue mass. Results were assessed
      by histological staining methods, fluorescent immune-histochemistry staining as
      well photos by scanning electron microscopy (SEM) to demonstrate the adhesion and
      growth of cells in the fibrin gel. This result opens a real possibility for
      future clinical applications in the treatment of reconstructive and regenerative
      medicine where the use of stem cell may eventually be a unique solution or in the
      field of aesthetic medicine where autograft fat stem cells may grant for a safer
      and better outcome with long lasting results.

PMID- 22395738
TI  - An interview with Angela Nieto. Interviewed by Eva Amsen.
AB  - Angela Nieto is Full Professor at the Instituto de Neurociencias (CSIC-UMH) in
      Alicante, Spain, and Head of the institute's Developmental Neurobiology Unit. She
      is also the current president of the Spanish Society for Developmental Biology
      (Sociedad Espanola de Biologia del Desarollo, SEBD). We interviewed her to talk
      about the plans of the SEBD for the coming years.

PMID- 22395740
TI  - OCTOPUS, a polarly localised membrane-associated protein, regulates phloem
      differentiation entry in Arabidopsis thaliana.
AB  - Vascular development is embedded into the developmental context of plant organ
      differentiation and can be divided into the consecutive phases of vascular
      patterning and differentiation of specific vascular cell types (phloem and
      xylem). To date, only very few genetic determinants of phloem development are
      known. Here, we identify OCTOPUS (OPS) as a potentiator of phloem
      differentiation. OPS is a polarly localised membrane-associated protein that is
      initially expressed in provascular cells, and upon vascular cell type
      specification becomes restricted to the phloem cell lineage. OPS mutants display
      a reduction of cotyledon vascular pattern complexity and discontinuous phloem
      differentiation, whereas OPS overexpressers show accelerated progress of
      cotyledon vascular patterning and phloem differentiation. We propose that OPS
      participates in vascular differentiation by interpreting longitudinal signals
      that lead to the transformation of vascular initials into differentiating
      protophloem cells.

PMID- 22395741
TI  - Regulation of cranial morphogenesis and cell fate at the neural crest-mesoderm
      boundary by engrailed 1.
AB  - The characterization of mesenchymal progenitors is central to understanding
      development, postnatal pathology and evolutionary adaptability. The precise
      identity of the mesenchymal precursors that generate the coronal suture, an
      important structural boundary in mammalian skull development, remains unclear. We
      show in mouse that coronal suture progenitors originate from hedgehog-responsive
      cephalic paraxial mesoderm (Mes) cells, which migrate rapidly to a supraorbital
      domain and establish a unidirectional lineage boundary with neural crest (NeuC)
      mesenchyme. Lineage tracing reveals clonal and stereotypical expansion of
      supraorbital mesenchymal cells to form the coronal suture between E11.0 and
      E13.5. We identify engrailed 1 (En1) as a necessary regulator of cell movement
      and NeuC/Mes lineage boundary positioning during coronal suture formation. In
      addition, we provide genetic evidence that En1 functions upstream of fibroblast
      growth factor receptor 2 (Fgfr2) in regulating early calvarial osteogenic
      differentiation, and postulate that it plays an additional role in precluding
      premature osteogenic conversion of the sutural mesenchyme.

PMID- 22395739
TI  - Fluid flows and forces in development: functions, features and biophysical
      principles.
AB  - Throughout morphogenesis, cells experience intracellular tensile and contractile
      forces on microscopic scales. Cells also experience extracellular forces, such as
      static forces mediated by the extracellular matrix and forces resulting from
      microscopic fluid flow. Although the biological ramifications of static forces
      have received much attention, little is known about the roles of fluid flows and
      forces during embryogenesis. Here, we focus on the microfluidic forces generated
      by cilia-driven fluid flow and heart-driven hemodynamics, as well as on the
      signaling pathways involved in flow sensing. We discuss recent studies that
      describe the functions and the biomechanical features of these fluid flows. These
      insights suggest that biological flow determines many aspects of cell behavior
      and identity through a specific set of physical stimuli and signaling pathways.

PMID- 22395743
TI  - Evidence-based treatments for smoking cessation.
AB  - Cigarette smoking continues to be the leading preventable cause of death in the
      United States. Nurse practitioners play an important role in implementing
      effective smoking cessation treatments and educating patients about the
      associated risks of smoking.

PMID- 22395742
TI  - Walnut-like In2S3 microspheres: ionic liquid-assisted solvothermal synthesis,
      characterization and formation mechanism.
AB  - Walnut-like In(2)S(3) microspheres were synthesized through an ionic liquid
      assisted solvothermal method for the first time. The crystal structure and
      morphology of the as-synthesized products were characterized by X-ray diffraction
      (XRD), scanning electron microscopy (SEM), high-resolution transmission electron
      microscopy (HRTEM), energy-dispersive X-ray (EDX) spectroscopy, X-ray
      photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectra (DRS) and
      nitrogen adsorption-desorption measurement. It was found that the additional
      amount of ionic liquid, solvothermal temperature and time played crucial roles in
      controlling the structure and morphology of the In(2)S(3) microspheres. A
      possible formation mechanism of the walnut-like In(2)S(3) microsphere was
      proposed on the basis of the experimental results.

PMID- 22395744
TI  - Optimizing fibromyalgia management.
AB  - Fibromyalgia (FM) is a persistent pain state commonly diagnosed and managed by
      nurse practitioners. This article summarizes current information regarding the
      etiology, pathophysiology, clinical presentation, diagnostic standards, and
      pharmacologic and non-pharmacologic treatments necessary to successfully manage
      FM.

PMID- 22395745
TI  - The Nurse Practitioner salutes the DNP.

PMID- 22395746
TI  - [Nuclear medicine in Europe: education].
AB  - The technical developments that have taken place in the preceding years (PET,
      hybrid imaging) have changed nuclear medicine. The future cooperation with
      radiologists will be challenging as well as positioning nuclear medicine in an
      European context. It can also be expected that education in nuclear medicine will
      undergo a harmonization process in the states of the European Union.  In this
      paper, we describe how nuclear medicine education is organized in several
      European countries. We aim to stimulate constructive discussions on the future
      development of the specialization in nuclear medicine in Germany.

PMID- 22395747
TI  - Observations of muslim physicians regarding the influence of religion on health
      and their clinical approach.
AB  - Although most patients report wanting their physicians to address the religious
      aspects of their lives, most physicians do not initiate questions concerning
      religion with their patients. Although religion plays a major role in every
      aspect of the life of a Muslim, most of the data on the role of religion in
      health have been conducted in populations that are predominantly non-Muslim. The
      objectives of this study were to assess Muslim physicians' beliefs and behaviours
      regarding religious discussions in clinical practice and to understand the
      factors that facilitate or impede discussion of religion in clinical settings.
      The study is based on a cross-sectional survey. Muslim physicians working in a
      tertiary care hospital in Saudi Arabia were invited to complete a questionnaire
      that included demographic data; intrinsic level of religiosity; beliefs about the
      impact of religion on health; and observations, attitudes, behaviours, and
      barriers to attending to patients' religious needs. Out of 225 physicians, 91%
      agreed that religion had a positive influence on health, but 62.2% thought that
      religion could lead to the refusal of medically indicated therapy. Over half of
      the physicians queried never asked about religious issues. Family physicians were
      more likely to initiate religious discussions, and physicians with high intrinsic
      religiosity were more likely to share their own religious views. Residents and
      staff physicians tended to avoid such discussions. The study results highlight
      the fact that many physicians do not address patients' religious issues and that
      there is a need to clarify ethically sound means by which to address such needs
      in Islamic countries. Medical institutions should work to improve the capacity of
      medical personnel to appropriately address religious issues. The training of
      clinical religious advisors is a promising solution to this dilemma.

PMID- 22395748
TI  - Humility, lifetime trauma, and change in religious doubt among older adults.
AB  - Compared to research on the positive or beneficial effects of religion on health,
      far fewer studies have been designed to examine the potentially negative aspects
      of religion. The purpose of this study is to examine a potentially negative part
      of leading a religious life--religious doubt. More specifically, the current
      study was designed to assess the relationships among humility, exposure to
      lifetime trauma, and change in religious doubt over time. Two hypotheses were
      developed to explore the relationships among these constructs. The first
      hypothesis predicts that greater exposure to traumatic events at any point in the
      life course will be associated with greater doubts about religion over time. The
      second hypothesis proposes that the potentially deleterious effects of exposure
      to lifetime trauma will be buffered or offset for individuals who are more
      humble. Findings from a nationwide, longitudinal survey of older adults provide
      support for both hypotheses. This appears to be the first time that the
      relationship among humility, lifetime trauma, and change in religious doubt has
      been evaluated empirically.

PMID- 22395749
TI  - Loving thyself: a Kohutian interpretation of a "limited" mature narcissism in
      evangelical megachurches.
AB  - Evangelical megachurches across the United States provide a subculture for core
      and committed members who immerse themselves in these communities of faith. This
      article argues that American evangelical megachurches fail to mitigate "the
      narcissism epidemic" in the dominant secular culture. Using object relations
      theory, I discuss splitting as a psychological foundation for narcissism, and I
      employ Heinz Kohut's self-psychology to analyze idealized, mirroring, and
      twinning self-objects in evangelical megachurches. Finally, given Kohut's
      categories for a mature narcissism, I find that Evangelicals achieve creativity,
      empathy, transience, humor, and wisdom, in part, but their ideological
      frameworks, organizational characteristics, and beliefs challenge a
      transformation to mature narcissism.

PMID- 22395750
TI  - Adolescent sexual risk-taking in the informal settlements of Nairobi, Kenya:
      understanding the contributions of religion.
AB  - Young people in sub-Saharan Africa are at the centre of the global HIV epidemic
      as they account for a disproportionate share of new infections. Their
      vulnerability to HIV has been attributed to a myriad of factors, in particular,
      risky sexual behaviours. While economic factors are important, increasing
      attention has been devoted to religion on the discourse on sexual decision-making
      because religious values provide a perspective on life that often conflicts with
      risky sexual behaviours. Given the centrality of religion in the African social
      fabric, this study assesses the relationship between adolescent religiousness and
      involvement in risky sexual behaviours using data from the informal settlements
      of Nairobi. Guided by social control theory, the paper explores if and how
      religion and religiosity affect sexual risk-taking among adolescents. 

PMID- 22395751
TI  - Good God?!? Lamentations as a model for mourning the loss of the good God.
AB  - This article will address the devastating psychological and social effects due to
      the loss of one's primary love-object, namely God in the case of faith
      communities and religious individuals. By using Melanie Klein's Object Relations
      Theory (Klein in Envy and gratitude and other works 1946/1963. The Free Press,
      New York, 1975a) as a way to enter the text of Lamentations, I will articulate an
      alternative reading that can serve as a model for Pastors and Educators to use
      when walking with individuals and communities through unspeakable losses. I will
      argue that Lamentations may be used as a tool for naming confounding depression
      and anxiety that stems from a damaged introjected object (one's personal God).
      This tool may provide individuals and communities a framework for placing anger
      and contempt upon God in order to re-assimilate this loved yet hated object,
      eventually leading toward healing and restoration of the self.

PMID- 22395752
TI  - Abuse in childhood and religious/spiritual status in adulthood among internal
      medicine outpatients.
AB  - The relationship between abuse in childhood and religiosity/spirituality status
      in adulthood has been previously studied, but not in a medical sample or with the
      current study measure. Using a cross-sectional consecutive sample of 317 internal
      medicine outpatients, we asked participants, "As a child, were you the victim of
      either physical or sexual abuse?," and assessed religiosity/spirituality status
      with the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being
      Scale (FACIT-Sp-12). We found that among the cohort with abuse in childhood,
      seven of twelve scales as well as the overall FACIT-Sp-12 score demonstrated
      statistically significant differences, with abused participants consistently
      evidencing lower religiosity/spirituality scores. 

PMID- 22395753
TI  - Spirituality in occupational therapy: do we practice what we teach?
AB  - This mixed-method study examined the responses of 97 occupational therapists on
      the subject of spirituality in occupational therapy practice. The inclusion of
      spirituality into the Occupational Therapy Practice Framework (2008) implies that
      clinicians address spirituality as a component of client-centered practice. This
      research revealed a gap between education, theory, and practice as evidenced in
      the quantitative and qualitative data. Although occupational therapy is intended
      to be holistic, therapists require a more complete understanding of what
      spirituality is and what the role of the occupational therapist is when
      addressing spirituality in evaluation or treatment. The discussion of this
      research provides information for future occupational therapy educators and
      educational programs as they seek to incorporate the construct of spirituality
      into curricula. 

PMID- 22395754
TI  - The use of narrative in Jewish medical ethics.
AB  - Anne Jones has pointed out that over the last three decades, stories have been
      important to medical ethics in at least three ways: (1). Stories as cases for
      teaching principle-based medical ethics (2). Narratives for moral guides on what
      is considered living a good life (3). Stories as testimonials written by both
      patients and physicians. A pioneer in this effort, particularly in regard to
      using narratives as moral guides, has been the ethicist and philosopher Stanley
      Hauerwas. Heavily influenced by virtue ethics, Hauerwas believes that it is a
      person's particular narrative tradition that provides one with convictions that
      form the basis of one's morality. Befitting a Protestant theologian, he is
      particularly concerned with the Christian narrative. From a Jewish perspective,
      there has been much less written on the use of narrative in medical ethics.
      However, it is a mistake to think that narrative has little, if any, role in
      Rabbinic ethical decision making. The purpose of this article is to demonstrate
      the centrality of narrative in the thought of Orthodox Jewish decisors and the
      problems inherent in this methodology. 

PMID- 22395755
TI  - Scrupulosity and obsessive compulsive disorder: the cognitive perspective in
      Islamic sources.
AB  - A moral/religious subtype of obsessive compulsive disorder has been termed as
      scrupulosity by mental health professionals. Since ultimate feared consequence in
      scrupulous individuals is religious or moral in nature, it also presents
      interesting and difficult issue for religious authorities. This article focuses
      on various aspects of scrupulosity that have until now been poorly conceptualized
      in Islamic world and provides a conceptual cognitive framework and analysis of
      scrupulosity according to Islamic sources. 

PMID- 22395756
TI  - Rethinking psychosocial interventions in natural disasters: lessons from holistic
      ecocentrism and religious beliefs.
AB  - The history of thought has been determined by the understanding and regulation of
      the relationships among the human being, Nature and God. This trilogy
      traditionally consists of completely differentiated elements with suggestive
      implications in the aesthetic landscape experience. But it is possible to
      identify cultures in different parts of the world or historic moments
      characterized by the assimilation of humans as part of Nature, or Nature as part
      of God. These considerations are particularly important in the so-called
      "primitive" contemporary societies when devastating natural phenomenon occur,
      since the design of psychosocial intervention strategies could become linked to
      religious rituals. 

PMID- 22395757
TI  - Spirituality and religiosity in the aftermath of a natural catastrophe in Italy.
AB  - The aim of this study is to assess the influence of spirituality and
      religiousness on the psychological traumatic effects of a catastrophic event in a
      population that had been exposed to an earthquake compared with a control
      population that had not been exposed. A total of 901 people have been evaluated
      using: (1) Brief Multidimensional Measure of Religiousness/Spirituality; (2)
      Impact of Event Scale and (3) Trauma and Loss Spectrum-Self Report (TALS-SR).
      Self-perceptions of spirituality and religiousness were used to rank the samples,
      distinguishing between spiritual and religious, spiritual-only, religious-only
      and neither spiritual nor religious groups. The sample that had experienced the
      earthquake showed lower scores in spiritual dimension. The religious-only group
      of those who were exposed to the earthquake demonstrated TALS-SR re-experiencing
      and arousal domain scores similar to the population that was not exposed. A
      weakening of spiritual religiosity in people having difficulty coping with trauma
      is a consistent finding. We further observed that the religious dimension helped
      to buffer the community against psychological distress caused by the earthquake.
      The religiosity dimension can positively affect the ability to cope with
      traumatic experiences. 

PMID- 22395758
TI  - The health behavior of Sri Lankan Buddhist nuns with type 2 diabetes: duty,
      devotion, and detachment.
AB  - Sri Lanka has experienced an increase in the rate of type 2 diabetes.
      Selfmanagement of diabetes among Sri Lanka's Buddhist nuns, who depend on food
      donations and limit physical activity in accord with the monastic code of
      conduct, presents unique challenges and has not been previously studied. The
      purpose of this focused ethnographic study of 10 Buddhist nuns was to understand
      how they managed their illness within the restrictions on diet and physical
      activity. Three themes-duty, devotion, and detachment-explained and described
      their health behavior regarding type 2 diabetes within the context of their daily
      routines and obligations. 

PMID- 22395759
TI  - Rationalizing the approach to children with fever in neutropenia.
AB  - PURPOSE OF REVIEW: Fever in neutropenia is the most frequent potentially life
      threatening complication of chemotherapy in children and adolescents with cancer.
      This review summarizes recent studies that refine our knowledge of how to manage
      pediatric fever in neutropenia, and their implications for clinical practice and
      research. RECENT FINDINGS: Many studies have focused on improving risk
      stratification based on clinical and laboratory characteristics, and on stepping
      down treatment in low-risk episodes. New diagnostic strategies are in their
      infancy, including use of polymerase chain reaction (PCR) methods and cross
      sectional imaging. Increasing use of systematic review and meta-analysis has
      helped to consolidate research and to reduce or identify uncertainties in many
      areas. SUMMARY: Our understanding of the cause of fever in neutropenia has been
      improved by PCR-based diagnostics, but the clinical implications remain unclear.
      Many risk-prediction models have been developed, but none is useful for clinical
      practice as yet. First-day outpatient management, with oral or intravenous
      antibiotics, is now known to be efficacious and cost-effective for pediatric low
      risk fever in neutropenia. Before implementing this regimen as new standard of
      care, its safety should be assessed. Internationally supported evidence-based
      guidelines for pediatric fever in neutropenia are being developed. They have the
      potential to rationalize everyday practice, and stimulate further research.

PMID- 22395760
TI  - Do aspirin and statins prevent severe sepsis?
AB  - PURPOSE OF REVIEW: Sepsis is an inflammatory condition associated with
      significant morbidity and mortality. Given the lack of specific therapies for the
      condition, prevention has garnered significant interest and increased importance.
      The article reviews the current literature regarding the use of aspirin and
      statins for the prevention of sepsis. RECENT FINDINGS: Aspirin and statins have
      been integral in the prevention of atherosclerotic disease. Additionally, statins
      have proven beneficial in the prevention of nonatherosclerotic conditions
      secondary to their pleiotropic effects. In animal models, this pleiotropism
      modulates many inflammatory pathways of sepsis. The platelet also plays an
      integral role in this inflammatory cascade of sepsis. Scientific data indicates
      that antiplatelet therapy, including aspirin, may attenuate these undesirable
      effects of platelets. Finally, observational studies have shown that patients
      taking statins have a decreased incidence of sepsis and septic shock, and aspirin
      may potentiate these benefits. SUMMARY: Sepsis is a deadly and costly condition
      with no available, specific treatment options. The statins and aspirin are well
      tolerated and widely used for prevention of cardiovascular disease. Because of
      their effects on the immune system and inflammatory pathways, they may present
      viable medical options for the prevention of sepsis.

PMID- 22395761
TI  - Current concepts on the pathogenesis of Escherichia coli meningitis: 
      implications for therapy and prevention.
AB  - PURPOSE OF REVIEW: Neonatal Escherichia coli meningitis continues to be an
      important cause of mortality and morbidity throughout the world. The major
      contributing factors to this mortality and morbidity include our incomplete
      knowledge on its pathogenesis and an emergence of antimicrobial-resistant E.
      coli. Recent reports of neonatal meningitis caused by E. coli producing CTX-M
      type or TEM-type extended-spectrum beta-lactamases create a challenge, and
      innovative approaches are needed to identify potential targets for prevention and
      therapy of E. coli meningitis. RECENT FINDINGS: E. coli invasion of the blood
      brain barrier is a prerequisite for penetration into the brain and requires
      specific microbial-host factors as well as microbe-specific and host-specific
      signaling molecules. Recent studies identified additional microbial and host
      factors contributing to E. coli invasion of the blood-brain barrier and
      elucidated their underlying mechanisms. Blockade of the microbial-host factors
      contributing to E. coli invasion of the blood-brain barrier was shown to be
      efficient in preventing E. coli penetration into the brain. SUMMARY: Continued
      investigation on the microbial-host factors contributing to E. coli invasion of
      the blood-brain barrier is needed to identify new targets for prevention and
      therapy of E. coli meningitis, thereby limiting the exposure to emerging
      antimicrobial-resistant E. coli.

PMID- 22395762
TI  - [Effects of a psychological group intervention on neuropsychiatric symptoms and
      communication in Alzheimer's dementia].
AB  - BACKGROUND: Outcomes of a multicomponent psychological intervention designed for
      the treatment of neuropsychiatric symptoms, communicative and emotional deficits
      in patients with mild to moderate Alzheimer's dementia were evaluated in a
      controlled trial. Core components of the program were milieu therapy
      interventions and music therapy. PATIENTS AND METHODS: A total of 49 patients
      were involved into a pre-post design. The treatment group (n=26) received the
      program for 6 months, while controls (n=23) participated in standard occupational
      therapy. Statistical analyses included t-tests, calculation of effect sizes, and
      two-way analyses of variance. RESULTS: After 6 months, the treatment group showed
      clear, partly significant improvement of anxiety, agitation, aggression, and
      apathy as well as social communication, emotional competence and activity levels
      relative to controls. CONCLUSION: The program has the potential to increase
      psychological well-being and to improve communication in patients with
      Alzheimer's dementia.

PMID- 22395763
TI  - Making the diagnosis of gastrointestinal GVHD: is evaluation of the ileum
      necessary?

PMID- 22395765
TI  - Association between gout and polymorphisms in GCKR in male Han Chinese.
AB  - Several genome-wide association studies (GWASs) have reported associations
      between single nucleotide polymorphisms (SNPs) and uric acid concentrations or
      gout in a number of different ethnic populations. To clarify the global relevance
      of the previously identified SNPs in the development of the qualitative trait
      gout, in the present study, the associations between two SNPs in the glucokinase
      (hexokinase 4) regulator (GCKR) gene and gout were assessed in a male Chinese Han
      population. The study population comprised 476 male gout patients and 465 male
      controls. Multiple PCR was performed using time-of-flight mass spectrometry
      (MALDI-TOF MS) to identify genotypes. Two SNPs, rs780093 and rs780094, located in
      intronic regions of the GCKR gene were found to be significantly associated with
      the development of gout. Thus, the association between the two GCKR SNPs and gout
      was replicated in the male Han Chinese population investigated in the present
      study. Furthermore, GCKR was identified as a novel candidate gene associated with
      gout.

PMID- 22395764
TI  - Recommended screening and preventive practices for long-term survivors after
      hematopoietic cell transplantation.
AB  - Advances in hematopoietic cell transplantation (HCT) technology and supportive
      care techniques have led to improvements in long-term survival after HCT.
      Emerging indications for transplantation, introduction of newer graft sources
      (for example, umbilical cord blood) and transplantation of older patients using
      less intense conditioning regimens have also contributed to an increase in the
      number of HCT survivors. These survivors are at risk for developing late
      complications secondary to pre-, peri- and post-transplant exposures and risk
      factors. Guidelines for screening and preventive practices for HCT survivors were
      published in 2006. An international group of transplant experts was convened in
      2011 to review contemporary literature and update the recommendations while
      considering the changing practice of transplantation and international
      applicability of these guidelines. This report provides the updated
      recommendations for screening and preventive practices for pediatric and adult
      survivors of autologous and allogeneic HCT.

PMID- 22395766
TI  - Enabling high grayscale resolution displays and accurate response time
      measurements on conventional computers.
AB  - Display systems based on conventional computer graphics cards are capable of
      generating images with 8-bit gray level resolution. However, most experiments in
      vision research require displays with more than 12 bits of luminance resolution.
      Several solutions are available. Bit++ (1) and DataPixx (2) use the Digital
      Visual Interface (DVI) output from graphics cards and high resolution (14 or 16
      bit) digital-to-analog converters to drive analog display devices. The
      VideoSwitcher (3) described here combines analog video signals from the red and
      blue channels of graphics cards with different weights using a passive resister
      network (4) and an active circuit to deliver identical video signals to the three
      channels of color monitors. The method provides an inexpensive way to enable high
      resolution monochromatic displays using conventional graphics cards and analog
      monitors. It can also provide trigger signals that can be used to mark stimulus
      onsets, making it easy to synchronize visual displays with physiological
      recordings or response time measurements.    Although computer keyboards and mice
      are frequently used in measuring response times (RT), the accuracy of these
      measurements is quite low. The RTbox is a specialized hardware and software
      solution for accurate RT measurements. Connected to the host computer through a
      USB connection, the driver of the RTbox is compatible with all conventional
      operating systems. It uses a microprocessor and high-resolution clock to record
      the identities and timing of button events, which are buffered until the host
      computer retrieves them. The recorded button events are not affected by potential
      timing uncertainties or biases associated with data transmission and processing
      in the host computer. The asynchronous storage greatly simplifies the design of
      user programs. Several methods are available to synchronize the clocks of the
      RTbox and the host computer. The RTbox can also receive external triggers and be
      used to measure RT with respect to external events.     Both VideoSwitcher and
      RTbox are available for users to purchase. The relevant information and many
      demonstration programs can be found at http://lobes.usc.edu/.

PMID- 22395767
TI  - Efficacy of tooth bleaching with and without light activation and its effect on
      the pulp temperature: an in vitro study.
AB  - The aim of this in vitro study was to evaluate the colour stability of bleaching
      after light activation with halogen unit, laser, LED unit or chemical activation
      up to 3 months after treatment. Four groups of teeth (n = 20) were bleached with
      Opalescence Xtra Boost (38% hydrogen peroxide) using four different methods:
      activation with halogen, LED, laser or chemical activation only. All teeth were
      bleached in one session for four times (4 * 15 min) and the colour was evaluated
      using a spectrophotometer at the following time points: before bleaching,
      immediately after bleaching, 1 day, and 1 and 3 months after the end of
      bleaching. Between the tested time points, the teeth were stored in 0.9% NaCl
      solution. Additionally, the temperature increase in the pulp chamber was measured
      using a measuring sensor connected to a computer. Bleaching with the halogen unit
      showed the highest colour change. Halogen unit, laser and chemical activation
      resulted in whiter teeth after 1 and 3 months compared to the colour after the
      end of the bleaching procedure (p <= 0.05). Three months after the end of
      bleaching, the shade changes observed were-halogen: 7.1 > chemical activation:
      6.2 > LED: 5.4 > laser: 5.2. Halogen showed the highest temperature increase
      (17.39 degrees C +/- 1.96) followed by laser (14.06 degrees C +/- 2.55) and LED
      (0.41 degrees C +/- 0.66) (p < 0.0001). Chemical activation did not affect the
      temperature in the pulp chamber. The use of light activation did not show any
      advantages compared to chemical bleaching. Although halogen unit showed the
      higher shade's change, its use resulted also in the higher pulp temperature.
      According to the present findings, light activation of the bleaching agent seems
      not to be beneficial compared to bleaching without light activation, concerning
      the colour stability up to 3 months after bleaching and the pulp temperature
      caused during the bleaching procedure.

PMID- 22395768
TI  - Treatment of dual diagnosis disorders.
AB  - PURPOSE OF REVIEW: Treatment of dual diagnosis [co-occurrence of a substance use
      disorder (SUD) in patients with mental illness] poses several challenges for
      mental health professionals. This article seeks to review the recent advances in
      dual diagnosis treatment with respect to pharmacotherapy and psychosocial
      approaches. RECENT FINDINGS: Atypical antipsychotics are commonly used for
      comorbid schizophrenia and SUD. Whereas there is no difference between
      risperidone and olanzapine, clozapine appears to have a distinct advantage in
      reducing psychotic symptoms as well as substance abuse (including smoking). There
      is emerging evidence that quetiapine is beneficial in dually diagnosed patients,
      particularly using alcohol, cocaine and amphetamine. A combination of naltrexone
      and sertraline was found to be effective in patients with depressive disorder and
      alcohol dependence. Effectiveness of atomoxetine is yet to be established in
      patients with comorbid adult attention-deficit/hyperactivity disorder with
      respect to decrease in substance abuse. Integrated intervention is the choice of
      treatment for patients with dual diagnosis. SUMMARY: In spite of the high
      association between substance use and psychiatric disorders, there is a
      surprising paucity of studies related to treatment and outcome. A few well
      designed studies have been recently published and more studies of this nature are
      required in order to address the challenges posed in the treatment of dual
      disorders.

PMID- 22395769
TI  - Hepatitis C and substance use:  new treatments and novel approaches.
AB  - PURPOSE OF REVIEW: To provide an update on new treatment approaches for patients
      with hepatitis C virus (HCV) infection and substance use. This issue is of
      extreme importance for HCV, as many patients have substance-use histories. RECENT
      FINDINGS: Recent emergence of two new protease inhibitors, boceprevir and
      telaprevir, to enhance the modern treatment of HCV have boosted the sustained
      virologic response rate to about 80%, a 30% increase over prior standard of care
      with interferon and ribavirin. Unfortunately, many providers are reluctant to
      treat patients with substance-use histories unless they have demonstrated
      abstinence for at least 6 months, and there is a spoken and unspoken bias against
      these patients. Emerging new studies have shown that even current injection drug
      users can be treated successfully with results comparable to patients who are
      abstinent and those with no drug-use histories, especially with attention to the
      patient's substance use and other psychiatric problems. SUMMARY: Newer treatment
      approaches for HCV will help many more patients than ever before to overcome the
      virus. Changed attitudes and innovative approaches to patients with substance-use
      histories are needed to bring these scientific advances to this segment of the
      population of patients with HCV.

PMID- 22395770
TI  - High positive predictive value of PAPP-A for acute coronary syndrome diagnosis in
      heparin-naive patients.
AB  - Pregnancy-associated plasma protein-A (PAPP-A) was studied as a marker of acute
      coronary syndrome (ACS). It has been shown that its levels are increased by
      heparin administration. Therefore, the aim of our study was to ascertain the
      diagnostic significance of PAPP-A in heparin-naive patients and compare it with
      (TnI). We prospectively studied 67 heparin-naive patients with acute chest pain.
      The patients were independently grouped according to the presence or absence of
      ACS. PAPP-A levels were significantly increased in ACS patients (8.6 vs. 7.3
      mIU/l; P = 0.006) with high positive (95.7%) and lower negative predictive values
      (47.7%). In multivariate analysis, its levels were strongly predictive of a final
      diagnosis of ACS (OR 41.8; 95th CI 2.64-662.6; P = 0.008). The diagnostic
      significance of PAPP-A was not higher than TnI even within 6 h after the onset of
      chest pain [the area under the ROC curve (AUC) was 0.69 for PAPP-A and 0.91 for
      TnI, respectively; P = 0.08]. We observed no difference in the AUC in NSTE-ACS
      patients (0.73 for PAPP-A and 0.79 for TnI (P = 0.5)). PAPP-A levels were an
      independent predictor of ACS diagnosis in heparin-naive patients. Its diagnostic
      significance was not higher than TnI even within a short period after the onset
      of chest pain. In troponin-negative NSTE-ACS patients, PAPP-A helped make the
      correct final diagnosis.

PMID- 22395771
TI  - In situ FTIR study on the formation and adsorption of CO on alumina-supported
      noble metal catalysts from H2 and CO2 in the presence of water vapor at high
      pressures.
AB  - The formation and adsorption of CO from CO(2) and H(2) at high pressures were
      studied over alumina-supported noble metal catalysts (Pt, Pd, Rh, Ru) by in situ
      FTIR measurements. To examine the effects of surface structure of supported metal
      particles and water vapor on the CO adsorption, FTIR spectra were collected at
      323 K with untreated and heat (673 K) treated catalysts in the absence and
      presence of water (H(2)O, D(2)O). It was observed that the adsorption of CO
      occurred on all the metal catalysts at high pressures, some CO species still
      remained adsorbed under ambient conditions after the high pressure FTIR
      measurements, and the frequencies of the adsorbed CO species were lower either
      for the heat treated samples or in the presence of water vapor. It is assumed
      that the CO absorption bands on atomically smoother surfaces appear at lower
      frequencies and that water molecules are adsorbed more preferentially on
      atomically rough surfaces rather than CO species.

PMID- 22395772
TI  - A two-way street: reciprocal regulation of metabolism and signalling.
AB  - It is becoming increasingly clear that cellular signalling and metabolism are not
      just separate entities but rather are tightly linked. Although nutrient
      metabolism is known to be regulated by signal transduction, an emerging paradigm
      is that signalling and transcriptional networks can be modulated by nutrient
      sensitive protein modifications, such as acetylation and glycosylation, which
      depend on the availability of acetyl-CoA and sugar donors such as UDP-N
      acetylglucosamine (UDP-GlcNAc), respectively. The integration of metabolic and
      signalling cues allows cells to modulate activities such as metabolism, cell
      survival and proliferation according to their intracellular metabolic resources.

PMID- 22395774
TI  - Update on fundoplication for the treatment of GERD.
AB  - Rudolph Nissen firstly implemented the idea of surgical treatment of
      gastroesophageal reflux more than 55 years ago. Today, laparoscopic
      fundoplication has become the surgical "golden standard" for the treatment of
      GERD. However, the initial enthusiasm and increasing number of performed
      procedures in the early 1990s declined dramatically between 2000 and 2006.
      Despite its excellent outcome, laparoscopic fundoplication is only offered to a
      minority of patients who are suffering from GERD. In this article we review the
      current indications for antireflux surgery, technical and intraoperative aspects
      of fundoplication, perioperative complications as well as short and long-term
      outcome. The focus is on the laparoscopic approach as the current surgical
      procedure of choice.

PMID- 22395773
TI  - Sirtuins as regulators of metabolism and healthspan.
AB  - Since the beginning of the century, the mammalian sirtuin protein family
      (comprising SIRT1-SIRT7) has received much attention for its regulatory role,
      mainly in metabolism and ageing. Sirtuins act in different cellular compartments:
      they deacetylate histones and several transcriptional regulators in the nucleus,
      but also specific proteins in other cellular compartments, such as in the
      cytoplasm and in mitochondria. As a consequence, sirtuins regulate fat and
      glucose metabolism in response to physiological changes in energy levels, thereby
      acting as crucial regulators of the network that controls energy homeostasis and
      as such determines healthspan.

PMID- 22395775
TI  - Human platelet lysate as a fetal bovine serum substitute improves human adipose
      derived stromal cell culture for future cardiac repair applications.
AB  - Adipose-derived stromal cells (ASC) are promising candidates for cell therapy,
      for example to treat myocardial infarction. Commonly, fetal bovine serum (FBS) is
      used in ASC culturing. However, FBS has several disadvantages. Its effects differ
      between batches and, when applied clinically, transmission of pathogens and
      antibody development against FBS are possible. In this study, we investigated
      whether FBS can be substituted by human platelet lysate (PL) in ASC culture,
      without affecting functional capacities particularly important for cardiac repair
      application of ASC. We found that PL-cultured ASC had a significant 3-fold
      increased proliferation rate and a significantly higher attachment to tissue
      culture plastic as well as to endothelial cells compared with FBS-cultured ASC.
      PL-cultured ASC remained a significant 25% smaller than FBS-cultured ASC. Both
      showed a comparable surface marker profile, with the exception of significantly
      higher levels of CD73, CD90, and CD166 on PL-cultured ASC. PL-cultured ASC showed
      a significantly higher migration rate compared with FBS-cultured ASC in a
      transwell assay. Finally, FBS- and PL-cultured ASC had a similar high capacity to
      differentiate towards cardiomyocytes. In conclusion, this study showed that
      culturing ASC is more favorable in PL-supplemented medium compared with FBS
      supplemented medium.

PMID- 22395776
TI  - Multiple identification and risks: examination of peer factors across multiracial
      and single-race youth.
AB  - Multiracial youth are thought to be more vulnerable to peer-related risk factors
      than are single-race youth. However, there have been surprisingly few well
      designed studies on this topic. This study empirically investigated the extent to
      which multiracial youth are at higher risk for peer influenced problem behavior.
      Data are from a representative and longitudinal sample of youth from Washington
      State (N = 1,760, mean age = 14.13, 50.9% girls). Of those in the sample, 225
      youth self-identified as multiracial (12.8%), 1,259 as White (71.5%), 152 as
      Latino (8.6%), and 124 as Asian American (7.1%). Results show that multiracial
      youth have higher rates of violence and alcohol use than Whites and more
      marijuana use than Asian Americans. Higher levels of socioeconomic disadvantage
      and single-parent family status partly explained the higher rates of problem
      behaviors among multiracial youth. Peer risk factors of substance-using or
      antisocial friends were higher for multiracial youth than Whites, even after
      socioeconomic variables were accounted for, demonstrating a higher rate of peer
      risks among multiracial youth. The number of substance-using friends was the most
      consistently significant correlate and predictor of problems and was highest
      among multiracial youth. However, interaction tests did not provide consistent
      evidence of a stronger influence of peer risks among multiracial youth. Findings
      underscore the importance of a differentiated understanding of vulnerability in
      order to better target prevention and intervention efforts as well as the need
      for further research that can help identify and explain the unique experiences
      and vulnerabilities of multiracial youth.

PMID- 22395777
TI  - Comparison between ATS/ERS age- and gender-adjusted criteria and GOLD criteria
      for the detection of irreversible airway obstruction in chronic heart failure.
AB  - BACKGROUND: Global Initiative for Chronic Obstructive Lung Disease (GOLD)
      criteria (FEV1/FVC <70%) are extensively used for diagnosis of chronic
      obstructive lung disease in heart failure (HF). The American Thoracic Society
      (ATS)/European Respiratory Society (ERS) recommends the use of age- and gender
      specific lower limit of normal (LLN) for FEV1/FVC. We compared the impact of
      these definitions on apparent prevalence of airway obstruction in chronic HF.
      METHODS: Standardized pre- and post-bronchodilator spirometry was performed in HF
      patients. Airway obstruction was defined by ATS/ERS criteria as diagnostic
      standard. Additionally, airway obstruction was calculated using the GOLD
      criteria. RESULTS: Of the 89 participants who fulfilled the ATS criteria for
      acceptability and reproducibility, 24.7% met ATS/ERS and 43.8% GOLD criteria for
      airway obstruction (Chi-square p = 0.007, McNemar <0.001). Sensitivity of GOLD
      criteria was 100%, specificity 74.6%, positive predictive value 56.4% and
      negative predictive value 100%. Among all individuals with an FEV1/FVC > LLN,
      25.4% were falsely identified when using the GOLD criteria. A majority of false
      positives qualified for airway obstruction GOLD stage I (FEV1% >=80%), which was
      significantly less often observed among true positives (76.5 vs. 31.8%; p <
      0.001). Only 31.8% of patients with irreversible airway obstruction detected by
      the ATS/ERS criteria reported a history of COPD. CONCLUSIONS: In all HF patients
      with persistent dyspnoea despite optimal HF treatment, spirometric testing should
      be performed. Application of the GOLD criteria leads to overdiagnosis of
      irreversible airway obstruction in patients with HF, which may result in
      inappropriate medical therapy and health-care decisions.

PMID- 22395778
TI  - Silver self aggregation in a nanodevice for enhanced Raman spectroscopy:
      experiments vs. simplified modeling via molecular dynamics.
AB  - We present a study, via experiments and exploratory molecular dynamics
      simulations, of self aggregation in cylindrical nanostructures obtained
      experimentally by combining high resolution electron beam lithography with
      electroless silver deposition. This process is key to the fabrication of a
      nanolens device, where a strong surface enhancement can be exploited for Raman
      spectroscopy. In order to investigate the process, we introduce a simple
      theoretical model and compare the results of simulations with the fabricated
      silver nanostructures during the growth phase. Our simulations qualitatively
      agree with the experiments and allow a general characterization of the process at
      length scales smaller than those easily accessible by microscopy. We identify a
      geometrical parameter, the aspect ratio of the cylinder, that relates two
      different types of growth with different characteristics and, possibly, different
      Raman enhancements.

PMID- 22395779
TI  - Attenuation of the side effect profile of regadenoson: a randomized double
      blinded placebo-controlled study with aminophylline in patients undergoing
      myocardial perfusion imaging. "The ASSUAGE trial".
AB  - BACKGROUND: It is unknown whether the standardized intravenous aminophylline
      administration following regadenoson-stress can prevent the gastrointestinal and
      other adverse effects associated with regadenoson. METHODS: In a randomized,
      double-blinded, placebo-controlled clinical trial we compared the frequency and
      severity of regadenoson adverse effects in those who received 75 mg of
      intravenous aminophylline versus a matching placebo administered 2 minutes after
      regadenoson or 90 seconds post-radioisotope injection. RESULTS: 248 patients
      [44.8% women, mean age 62.2 (+/- 13.3) years] were randomized to receive
      aminophylline (124) or placebo (124). In the aminophylline arm, there was 50%
      reduction in the incidence of the primary endpoint of diarrhea and abdominal
      discomfort [11 (8.9%) vs 22 (17.7%), P = .04] and 70% reduction in the incidence
      of diarrhea [4 (3.2%) vs 13 (10.5%), P = .02]. Additionally, aminophylline use
      was associated with 34% reduction in the secondary endpoint of any regadenoson
      adverse effects [55 (44.4%) vs 83 (66.9%), P < .001] and 71% reduction in
      headache [9 (7.3%) vs 31 (25%), P < .001]. The stress protocol was better
      tolerated in the aminophylline group (P = .007). The quantitative summed
      difference score was similar in both study groups (P = .92). There were no excess
      adverse events in the aminophylline arm. CONCLUSIONS: This trial supports the
      routine administration of IV-aminophylline to reduce the frequency and severity
      of adverse effects associated with regadenoson-stress.

PMID- 22395780
TI  - Reproducibility and accuracy of non-invasive measurement of infarct size in mice
      with high-resolution PET/CT.
AB  - BACKGROUND: This study assessed the reproducibility and accuracy of 2-deoxy
      2[(18)F]fluoro-D-glucose ((18)F-FDG) for non-invasive quantification of
      myocardial infarct size in mice by a high-resolution positron emission tomography
      (PET)/computed tomography (CT) system. METHODS AND RESULTS: Mice were studied by
      (18)F-FDG PET/CT 1 week after induction of myocardial infarction by permanent
      coronary occlusion or sham procedure. In a subset of mice, PET/CT was repeated 2
      days apart to assess the reproducibility of infarct size measurements.
      Histological analysis was used as reference method to validate imaging data. The
      average difference in infarct size measurements between the first and the second
      study was -0.42% +/- 2.07% (95% confidence interval -2.6 to 1.75) with a
      repeatability coefficient of 4.05%. At Bland-Altman analysis, the lower and upper
      limits of agreement between the two repeated studies were -4.46% and 3.63%,
      respectively, and no correlation between difference and mean was found (P = .89).
      The concordance correlation coefficient was 0.99 (P < .001) and the intraclass
      coefficient of correlation was 0.99. A high correlation between PET/CT and
      histology was found for measurement of infarct size (P < .001). Using Bland
      Altman analysis, the mean difference in infarct size measurement (PET/CT minus
      histology) was 1.9% (95% confidence interval 0.94% to 2.86%). CONCLUSIONS: In a
      mice model of permanent coronary occlusion non-invasive measurement of infarct
      size with high-resolution (18)F-FDG, PET/CT has excellent reproducibility and
      accuracy. These findings support the use of this methodology in serial studies.

PMID- 22395782
TI  - Synthesis, structure and reactivity of 4-phosphanylated 1,3-dialkyl-imidazole-2
      thiones.
AB  - Selective formation of 4-phosphanylated 1,2-dialkyl imidazole-2-thiones 3a-f has
      been obtained via a lithiation followed by phosphanylation reaction. The
      reactivity of 3a-f was examined towards oxidation and complexation reactions. All
      products were unambiguously characterized by elemental analyses, spectroscopic
      and spectrometric methods including X-ray analysis (3a, 3b, 4b, 4d, 5b, 6a and
      6d).

PMID- 22395783
TI  - Bacterial genomes: habitat specificity and uncharted organisms.
AB  - The capability and speed in generating genomic data have increased profoundly
      since the release of the draft human genome in 2000. Additionally, sequencing
      costs have continued to plummet as the next generation of highly efficient
      sequencing technologies (next-generation sequencing) became available and
      commercial facilities promote market competition. However, new challenges have
      emerged as researchers attempt to efficiently process the massive amounts of
      sequence data being generated. First, the described genome sequences are
      unequally distributed among the branches of bacterial life and, second, bacterial
      pan-genomes are often not considered when setting aims for sequencing projects.
      Here, we propose that scientists should be concerned with attaining an improved
      equal representation of most of the bacterial tree of life organisms, at the
      genomic level. Moreover, they should take into account the natural variation that
      is often observed within bacterial species and the role of the often changing
      surrounding environment and natural selection pressures, which is central to
      bacterial speciation and genome evolution. Not only will such efforts contribute
      to our overall understanding of the microbial diversity extant in ecosystems as
      well as the structuring of the extant genomes, but they will also facilitate the
      development of better methods for (meta)genome annotation.

PMID- 22395784
TI  - Tropical soil bacterial communities in Malaysia: pH dominates in the equatorial
      tropics too.
AB  - The dominant factors controlling soil bacterial community variation within the
      tropics are poorly known. We sampled soils across a range of land use types-
      primary (unlogged) and logged forests and crop and pasture lands in Malaysia. PCR
      amplified soil DNA for the bacterial 16S rRNA gene targeting the V1-V3 region was
      pyrosequenced using the 454 Roche machine. We found that land use in itself has a
      weak but significant effect on the bacterial community composition. However,
      bacterial community composition and diversity was strongly correlated with soil
      properties, especially soil pH, total carbon, and C/N ratio. Soil pH was the best
      predictor of bacterial community composition and diversity across the various
      land use types, with the highest diversity close to neutral pH values. In
      addition, variation in phylogenetic structure of dominant lineages
      (Alphaproteobacteria, Beta/Gammaproteobacteria, Acidobacteria, and
      Actinobacteria) is also significantly correlated with soil pH. Together, these
      results confirm the importance of soil pH in structuring soil bacterial
      communities in Southeast Asia. Our results also suggest that unlike the general
      diversity pattern found for larger organisms, primary tropical forest is no
      richer in operational taxonomic units of soil bacteria than logged forest, and
      agricultural land (crop and pasture) is actually richer than primary forest,
      partly due to selection of more fertile soils that have higher pH for agriculture
      and the effects of soil liming raising pH.

PMID- 22395785
TI  - Quantitative and automated high-throughput genome-wide RNAi screens in C.
      elegans.
AB  - RNA interference is a powerful method to understand gene function, especially
      when conducted at a whole-genome scale and in a quantitative context. In C.
      elegans, gene function can be knocked down simply and efficiently by feeding
      worms with bacteria expressing a dsRNA corresponding to a specific gene (1).
      While the creation of libraries of RNAi clones covering most of the C. elegans
      genome (2,3) opened the way for true functional genomic studies (see for example
      (4-7)), most established methods are laborious. Moy and colleagues have developed
      semi-automated protocols that facilitate genome-wide screens (8). The approach
      relies on microscopic imaging and image analysis. Here we describe an alternative
      protocol for a high-throughput genome-wide screen, based on robotic handling of
      bacterial RNAi clones, quantitative analysis using the COPAS Biosort (Union
      Biometrica (UBI)), and an integrated software: the MBioLIMS (Laboratory
      Information Management System from Modul-Bio) a technology that provides
      increased throughput for data management and sample tracking. The method allows
      screens to be conducted on solid medium plates. This is particularly important
      for some studies, such as those addressing host-pathogen interactions in C.
      elegans, since certain microbes do not efficiently infect worms in liquid
      culture.     We show how the method can be used to quantify the importance of
      genes in anti-fungal innate immunity in C. elegans. In this case, the approach
      relies on the use of a transgenic strain carrying an epidermal infection
      inducible fluorescent reporter gene, with GFP under the control of the promoter
      of the antimicrobial peptide gene nlp 29  and a red fluorescent reporter that is
      expressed constitutively in the epidermis. The latter provides an internal
      control for the functional integrity of the epidermis and nonspecific transgene
      silencing(9). When control worms are infected by the fungus they fluoresce green.
      Knocking down by RNAi a gene required for nlp 29 expression results in diminished
      fluorescence after infection. Currently, this protocol allows more than 3,000
      RNAi clones to be tested and analyzed per week, opening the possibility of
      screening the entire genome in less than 2 months.

PMID- 22395786
TI  - Comparability of skinfold thickness to DXA whole-body total fat in their
      associations with serum triglycerides in youths.
AB  - OBJECTIVE: To determine the comparability of triceps and subscapular skinfold
      thicknesses with dual X-ray absorptiometry (DXA) whole-body total fat (kg) in
      relation to serum triglyceride (TG) levels and increased risk of elevated TG
      levels, and identified optimum skinfold cutoffs for screening purposes in US
      adolescents. SUBJECTS/METHODS: Data from triceps and subscapular skinfold
      thickness, DXA whole-body total fat and serum TGs were obtained from 1505 US
      adolescents ages 12.00-17.99 years, who participated in two continuous National
      Health and Nutrition Examination Survey (NHANES) cycles 2001-2004. Study
      associations were examined with linear and logistic models, and ROC (receiver
      operating characteristic) analyses were used to derive skinfold cutoffs for
      identifying the risk of elevated TG levels. RESULTS: Using area under the curves
      (AUCs) as metrics of prediction accuracy (with bootstrapped 95% CIs), no
      significant differences were found between skinfolds and DXA logistic models for
      predicting elevated TG levels. Similarly, skinfold and DXA models had comparable
      precision in predicting continuous serum TG from bootstrapped root mean squared
      errors for both sexes. Population-adjusted marginal mean estimates indicated that
      youths whose skinfolds are in the top quartile had TG levels within 83-108 mg/dl.
      Skinfold cutoffs for predicting elevated estimated TG using ROC analyses showed
      that cutoffs decreased with age and ranged from 13 to 30 mm for ages 12-17, in
      yearly intervals. CONCLUSION: Skinfold thicknesses were comparable to DXA whole
      body total fat in predicting serum TG levels. These skinfold cutoffs could be
      used in practical settings as a first pass screener for identifying US
      adolescents at risk of elevated serum TGs.

PMID- 22395787
TI  - Cellular neoplastic transformation induced by 916 MHz microwave radiation.
AB  - There has been growing concern about the possibility of adverse health effects
      resulting from exposure to microwave radiations, such as those emitted by mobile
      phones. The purpose of this study was to investigate the cellular neoplastic
      transformation effects of electromagnetic fields. 916 MHz continuous microwave
      was employed in our study to simulate the electromagnetic radiation of mobile
      phone. NIH/3T3 cells were adopted in our experiment due to their sensitivity to
      carcinogen or cancer promoter in environment. They were divided randomly into one
      control group and three microwave groups. The three microwave groups were exposed
      to 916 MHz EMF for 2 h per day with power density of 10, 50, and 90 w/m(2),
      respectively, in which 10 w/m(2) was close to intensity near the antenna of
      mobile phone. The morphology and proliferation of NIH/3T3 cells were examined and
      furthermore soft agar culture and animal carcinogenesis assay were carried out to
      determine the neoplastic promotion. Our experiments showed NIH/3T3 cells changed
      in morphology and proliferation after 5-8 weeks exposure and formed clone in soft
      agar culture after another 3-4 weeks depending on the exposure intensity. In the
      animal carcinogenesis study, lumps developed on the back of SCID mice after being
      inoculated into exposed NIH/3T3 cells for more than 4 weeks. The results indicate
      that microwave radiation can promote neoplastic transformation of NIH/3T3cells.

PMID- 22395788
TI  - Role of NOD2 in regulating the immune response to Aspergillus fumigatus.
AB  - BACKGROUND: The nucleotide-binding oligomerization domain-2 (NOD2) is a type of
      intracellular receptor recognizing the cell wall molecules of bacteria and
      inducing the innate immune response. Its role in defense against fungal infection
      remains uncertain. We thus investigated the role of the NOD2/RIP2 pathway in host
      responses to Aspergillus fumigatus (Af) in RAW264.7 cells. METHODS: RAW264.7
      cells were cultured and Af conidia were added to stimulate the cells. The dynamic
      mRNA and protein expressions of NOD2 and RIP2 kinase were examined by real-time
      PCR and Western blotting. The protein expressions of nuclear factor-kappaB (NF
      kappaB) and pro-inflammatory tumor necrosis factor-alpha and interleukin-8 were
      also investigated. Specific siRNA for NOD2 was synthesized and used to confirm
      the effect of NOD2 in the immune response to Af conidia. RESULTS: The stimulation
      of the cell line by Af conidia resulted in a significantly increased expression
      of NOD2 protein and RIP2 kinase. The production of NF-kappaB and downstream
      cytokines were also increased simultaneously. On knockdown of the NOD2 using RNA
      interference, the activation of NF-kappaB was interrupted and the production of
      cytokines was reduced in the cell line stimulated by Af conidia. CONCLUSION:
      These results suggested that Af conidia induced NF-kappaB activation in a NOD2
      dependent manner, which potentially contributed to the innate immune response.

PMID- 22395789
TI  - Late-presenting congenital diaphragmatic hernia: diagnostic pitfalls and outcome.
AB  - PURPOSE: We sought to review the presentation, diagnosis, and outcome of a series
      of children with late-presenting, congenital diaphragmatic hernias (CDH).
      METHODS: Bochdalek and Morgagni hernias that were diagnosed after 30 days of age,
      between January 1989 and December 2009, were reviewed retrospectively. A medical
      record review and telephone survey were conducted in 2010. RESULTS: Thirty-one
      subjects, diagnosed with CDH between 45 days and 13 years of age (mean, 16
      months), were reviewed. Bochdalek hernias were present in 18 (58%) and Morgagni
      hernias in 13 (42%). There were twenty (64%) left-sided, eight (26%) right-sided,
      and three (10%) bilateral CDH. Five (16%) had other congenital anomalies. Eight
      (25.8%), including a subject with strangulated intestine that required resection,
      were initially misdiagnosed, due mostly to failure to obtain or correctly
      interpret a chest radiograph. Thirty (97%) were repaired by an abdominal
      approach, including seven laparoscopic closures. Follow-up ranged from 1 to 20
      years (median, 7 years). All subjects survived without recurrence. Unlike
      neonatally diagnosed CDH, neither right-sided hernia, patch repair, nor
      associated esophageal atresia predicted morbidity. CONCLUSION: Although
      diagnostic delays may lead to morbidity, if late-presenting CDH are expeditiously
      identified and repaired, their outcome is very good, in contrast to those that
      present in neonates.

PMID- 22395790
TI  - Evaluation of novel urinary renal biomarkers: biological variation and reference
      change values.
AB  - A number of novel urinary biomarkers have been identified and partially qualified
      for use as markers for renal injury in rats. We used two multiplex assays for
      these novel biomarkers to quantify biomarker concentration in serial urine
      collections from rats of both sexes administered varying concentrations of
      cisplatin. From these data, we calculate inter-individual variation and reference
      ranges from predose animals and intra-individual variation and reference change
      values from undosed control animals. The biomarkers evaluated are albumin, alpha
      glutathione s-transferase, glutathione S-transferase-yb1, lipocalin-2, kidney
      injury molecule-1, osteopontin, and renal papillary antigen 1. For any creatinine
      corrected novel biomarkers, we found intra-individual variation to be no greater
      than 44% and inter-individual variation to be no greater than 46%. Reference
      change values for most corrected analytes (except osteopontin) were 50-100%,
      indicating that a >100% increase in analyte concentration between serial samples
      would be unlikely to be associated with inherent analytical or biological
      variation.

PMID- 22395791
TI  - Evaluation of potential gastrointestinal biomarkers in a PAK4 inhibitor-treated
      preclinical toxicity model to address unmonitorable gastrointestinal toxicity.
AB  - Although gastrointestinal (GI) toxicity is a significant dose-limiting safety
      concern noted in multiple therapeutic areas, there are no GI biomarkers that can
      accurately track, precede, or reliably correlate with histologic evidence of
      injury. While significant efforts have been made within the pharmaceutical
      industry, academia, and consortia to address the biomarker gaps in other target
      organs such as liver, kidney, and muscle (cardiac and skeletal), there have been
      no concerted efforts in the area of GI biomarkers. Using PAK4 inhibitor as a
      preclinical rat model of gastric toxicity, selected candidate biomarkers from
      literature were evaluated to test their usefulness as gastric injury biomarkers
      in this study. Biomarkers selected in this study include plasma diamino oxidase
      and citrulline, fecal calprotectin, bile acids, and miRNA. Based on the results,
      L-citrulline and miR-194 results appear to correlate well with histopathology
      findings. Although these biomarkers will need additional assay validation and
      qualification to test if they truly predict the injury prior to histopathology,
      the results provide promise for further testing using additional GI toxicants. In
      addition, this article highlights important gaps in GI biomarkers and provides
      substrate and rationale for additional investments either for further testing of
      already available biomarkers or to pursue extensive biomarker discovery
      approaches.

PMID- 22395792
TI  - Association of renal tubular hyaline droplets with lymphoma in CD-1 mice.
AB  - In mice, hyaline droplets in renal proximal tubules have been associated with
      histiocytic sarcoma but have not been reported with lymphoma. Tissues from CD-1
      mice in a 2-year carcinogenicity bioassay were examined microscopically. Twenty
      five mice with hyaline droplets in renal tubules were identified.
      Immunohistochemistry to detect IgA, IgG, IgM, lysozyme, albumin, CD3, and CD79a
      was performed on kidneys of 21 affected mice. Hyaline droplets were present in
      the kidneys of 11 mice with lymphoma (1 male, 10 female), of which 1 female also
      had histiocytic sarcoma. Hyaline droplets were also present in 7 other mice with
      histiocytic sarcoma, 2 with chronic progressive nephropathy, 3 with renal
      cortical tubular necrosis, and 2 with granulocytic leukemia. Five of the 11
      lymphomas were CD3+, indicating a T lymphocyte origin. Hyaline droplets in mice
      with lymphoma did not stain for IgA, IgG, or IgM, except in one questionable
      case. Results of other immunohistochemical stains were inconclusive. Although the
      droplet composition could not be determined immunohistochemically, the study
      findings indicate that renal tubular hyaline droplets may be associated with
      lymphoma in mice.

PMID- 22395793
TI  - Effect of mastitis during the first lactation on production and reproduction
      performance of Holstein cows.
AB  - The aim of this study was to evaluate the effect of postpartum mastitis between
      first calving and subsequent conception on production and reproduction
      performance as well as culling of Holstein cows. A data set of 9,183 first
      lactation cows was used. Results showed that the first cumulative 100 days' milk
      production and the milk yield standardized to 305 days were affected by the
      interval from calving to first mastitis (P < 0.05). Cows with one episode of
      mastitis produced more milk than those with repeated episodes of mastitis (P <
      0.01). Increase in the number of mastitis episodes and also decrease in interval
      between first calving and mastitis increased services per conception (P < 0.001).
      Mastitis episode and the interval between calving and first mastitis had no
      apparent impact on the calving to conception interval (P > 0.05). Calving year,
      calving difficulty score, and cumulative first 60 days milk production had
      significant impacts on mastitis risk (P < 0.05). The interval from calving to the
      first incidence of mastitis decreased over the period studied (P < 0.001).
      Productive life tended to be decreased due to mastitis (P = 0.07). Survival
      analysis showed a significant difference between the lengths of productive life
      for cows with different intervals from calving to first mastitis (P < 0.01). The
      results demonstrated that clinical mastitis between first calving and conception
      reduced production and reproduction performance with an increase in chance of
      culling.

PMID- 22395794
TI  - PCR-SSCP analysis of leptin gene and its association with milk production traits
      in river buffalo (Bubalus bubalis).
AB  - Leptin gene has been found to be associated with various economic traits
      including milk production and fat quality in dairy animals. In the present study,
      we investigated genetic variations in intron 1 region of leptin gene in riverine
      buffaloes (Bubalus bubalis) using polymerase chain reaction-single strand
      conformation polymorphism (PCR-SSCP) and sequencing methods and associated them
      with milk traits. The study revealed three SSCP variants A, B and C among a total
      of 301 buffaloes from nine breeds. The frequency of variant C was found
      invariably high among all the breeds except in Marathwada buffalo. Variant A was
      found to be absent in Chilika, Nili-Ravi, Nagpuri and Pandharpuri breeds and also
      had the lowest frequencies in Mehsana, Jaffarabadi, Murrah and Toda breeds.
      Sequencing of SSCP variants revealed a total of five polymorphic sites, with
      three haplotypes. Statistical analysis revealed significantly high fat percentage
      at 150 days in SSCP variant B in Mehsana buffaloes. However, the associations of
      SSCP variants of leptin gene with total milk yield, 305 days milk yield and total
      fat yield were found to be non-significant. The present study is the first report
      on association analysis of leptin gene polymorphisms with milk production and
      milk quality traits in river buffalo.

PMID- 22395796
TI  - The skeptical technophile: iPad review.

PMID- 22395795
TI  - Activity and molecular dynamics relationship within the family of human
      cholinesterases.
AB  - The temperature dependence of the dynamics of recombinant human
      acetylcholinesterase (hAChE) and plasma human butyrylcholinesterase (hBChE) is
      examined using elastic incoherent neutron scattering. These two enzymes belong to
      the same family and present 50% amino acid sequence identity. However,
      significantly higher flexibility and catalytic activity of hAChE when compared to
      the ones of hBChE are measured. At the same time, the average height of the
      potential barrier to the motions is increased in the hBChE, e.g. more thermal
      energy is needed to cross it in the latter case, which might be the origin of the
      increase in activation energy and the reduction in the catalytic rate of hBChE
      observed experimentally. These results suggest that the motions on the picosecond
      timescale may act as a lubricant for those associated with activity occurring on
      a slower millisecond timescale. 

PMID- 22395797
TI  - The prevalence of primary headache disorders in Russia: a countrywide survey.
AB  - OBJECTIVE: To estimate the 1-year prevalences of primary headache disorders and
      identify their principal risk factors in the general population of Russia.
      METHODS: A countrywide population-based random sample of 2725 biologically
      unrelated adults in 35 cities and nine rural areas were interviewed in a door-to
      door survey using a previously validated diagnostic questionnaire. RESULTS: Of
      the 2725 eligible adults contacted, 2025 (74.3%) responded (females 52.6%, mean
      age 39.5 +/- 13.4 years). Of these, 1273 (62.9%) reported headache 'not related
      to flu, hangover, cold, head injury' occurring at least once in the previous
      year. The gender- and age-standardized 1-year prevalence of migraine was 20.8%.
      Female gender (odds ratio (OR) = 3.8; 95% confidence interval (CI) 2.8-5.1) and
      obesity (OR = 1.5; 1.1-2.1) were positively associated with this type of
      headache. The gender- and age-standardized 1-year prevalence of tension-type
      headache (TTH) was 30.8%. TTH was more prevalent in urban than in rural areas (OR
      = 1.6; 1.3-2.0). Headache on >=15 days/month was reported by 213 (10.5%)
      respondents (gender- and age-standardized prevalence 10.4%), and associated with
      low socioeconomic status (OR = 3.4; 2.4-4.9), obesity (OR = 3.0; 2.1-4.3), female
      gender (OR = 2.9; 2.1-4.1) and age over 40 years (OR = 2.6; 1.9-3.6). The
      majority of these respondents (68.1%) overused acute headache medications.
      CONCLUSION: The study demonstrated a high prevalence of migraine and a very high
      prevalence of headache on  >=15 days/month, and revealed unmet health-care needs
      of people with headache in Russia.

PMID- 22395799
TI  - Progress in primary aldosteronism 2.

PMID- 22395798
TI  - Migraine and restless legs syndrome in women.
AB  - BACKGROUND: Few clinic-based studies report an association between migraine and
      restless legs syndrome (RLS); however, population-based data are unavailable.
      METHODS: Cohort study among 31,370 women participating in the Women's Health
      Study. We had detailed self-reported information on migraine, including aura
      status, and RLS. RLS was ascertained at the 9-year follow-up. We calculated odds
      ratios (OR) and 95% confidence intervals (CI) for the association between
      migraine and RLS. We investigated any indication of migraine until RLS
      ascertainment as well as migraine with and without aura at baseline, prior
      migraine before baseline, and new reports of migraine during follow-up. RESULTS:
      At baseline or during follow-up 6857 (21.9%) women reported any migraine. These
      women had an increased risk for RLS (multivariable-adjusted OR = 1.22; 95%CI 1.13
      1.32). Further analyses indicated a similar association for migraine with aura
      (multivariable-adjusted OR = 1.27; 95%CI 1.10-1.48) and migraine without aura
      (multivariable-adjusted OR = 1.24; 95%CI 1.09-1.40) as well as for new reports of
      migraine during follow-up (multivariable-adjusted OR = 1.30; 95%CI 1.10-1.54).
      Prior migraine did not appear to be associated with RLS. CONCLUSIONS: Our data
      suggest an association between migraine and RLS at the population level. The
      association is similar for migraine with and without aura and for new reports of
      migraine during follow-up.

PMID- 22395800
TI  - Primary aldosteronism: the role of confirmatory tests.
AB  - The high prevalence of primary aldosteronism among hypertensives justifies large
      scale screening by the aldosterone-renin ratio; however, this test is subject to
      several variables responsible for false-positive results. Functional tests to
      confirm autonomous aldosterone secretion are commonly used, with the
      fludrocortisone suppression test considered the gold standard, and saline
      infusion or captopril challenge, the most practical. However, each of these tests
      has sub-optimal sensitivity and specificity and none has been so far
      prospectively validated by comparing the results with the lateralization by
      adrenal vein sampling and the results of surgery. Their role in confirming the
      diagnosis of primary aldosteronism due to unilateral adenoma remains incompletely
      resolved.

PMID- 22395801
TI  - Outcomes of adrenalectomy in patients with unilateral primary aldosteronism: a
      review.
AB  - Aldosterone hypersecretion in primary aldosteronism is unilateral (aldosterone
      producing adenoma and primary unilateral hyperplasia) or bilateral (idiopathic
      adrenal hyperplasia). Laparoscopic adrenalectomy is nowadays the preferred
      approach to treat patients with unilateral primary aldosteronism. We review the
      outcomes of this intervention in recently published series. Laparoscopic
      adrenalectomy has a morbidity of 5-14%, mortality below 1%, and a mean hospital
      stay around 3 days. It generally results in the normalization of aldosterone
      secretion and in a large decrease of blood pressure and antihypertensive
      medication, but normotension without treatment is only achieved in 42% of all
      cases. Normotension following adrenalectomy is more likely in young and lean
      women with recent low grade hypertension than in obese men with long-standing
      high grade hypertension or a family history of hypertension. However, individual
      prediction of the blood pressure outcome is not accurate and predictors of
      hypertension cure should not be used to select patients for surgery. Age,
      associated health conditions and preferences of the patient are more relevant to
      this end.

PMID- 22395802
TI  - [Screening for sleep apnea in cardiovascular patients in clinical routine].
AB  - Sleep apnea syndromes (SAS) are highly prevalent in cardiovascular patients.
      Because diagnostics are cost and labor intensive, these patients often remain
      undiagnosed. For this reason, simple screening methods for SAS in daily clinical
      practice are very important. Standardized questionnaires are one way to screen
      patients, i.e., simple standardized questionnaires have been shown to be highly
      predictive in OSA, but not in CSA patients. Simple ambulatory screening devices
      use oxymetry and/or nasal flow to determine the apnea-hypopnea index (AHI). These
      devices have been shown to be highly effective in screening for OSA and CSA. In
      addition, algorithms that calculate the electrocardiography (ECG)-derived AHI
      using heart rate variability and/or QRS morphology from Holter ECG recordings are
      also promising. Especially the latter method could become a simple tool for
      cardiologists to screen for SAS in clinical routine.

PMID- 22395803
TI  - [Editorial].

PMID- 22395805
TI  - Brain ageing: a fine balance.

PMID- 22395804
TI  - The ageing cortical synapse: hallmarks and implications for cognitive decline.
AB  - Normal ageing is associated with impairments in cognitive function, including
      memory. These impairments are linked, not to a loss of neurons in the forebrain,
      but to specific and relatively subtle synaptic alterations in the hippocampus and
      prefrontal cortex. Here, we review studies that have shed light on the cellular
      and synaptic changes observed in these brain structures during ageing that can be
      directly related to cognitive decline in young and aged animals. We also discuss
      the influence of the hormonal status on these age-related alterations and recent
      progress in the development of therapeutic strategies to limit the impact of
      ageing on memory and cognition in humans.

PMID- 22395807
TI  - Quantum dots impair macrophagic morphology and the ability of phagocytosis by
      inhibiting the Rho-associated kinase signaling.
AB  - Quantum dots (QDs) are fluorescent semiconductor nanoparticles that have broad
      excitation spectra, narrow emission peaks, long fluorescence lifetimes, and the
      ability to easily conjugate with bio-molecules. Due to these distinct
      characteristics, QDs represent promising substances in biological imaging and
      labelling. However, the side and adverse effects of QDs are also widely studied.
      Herein, we recognize macrophages as the pivotal cells in ingesting QDs, and that
      the accumulation of QDs inside macrophages leads to significant morphological
      alterations and a remarkable reduction of their ability to erythrophagocytize in
      vitro. In a mouse model with chronic exposure to QDs, red blood cell (RBC)
      retention in spleens and severe splenomegaly were observed, presumably due to
      attenuated macrophagic erythrophagocytosis in vivo. Importantly, we demonstrated
      that QDs greatly inhibited the Rho-associated kinase (ROCK) activity, resulting
      in impaired fidelity of the actin cytoskeleton and actin-rich structure (such as
      surface protrusions), which was assumed to be the molecular basis underlying the
      blunted macrophagic morphology and reduced ability to phagocytize. The combined
      data provide insights into QDs' intracellular trafficking, localization and
      biological fate in macrophages, and the resultant impairment to cytoskeleton
      coupled with inhibition on the ROCK signalling would decrease the macrophagic
      ability to erythrophagocytize with diminished RBC recycling and splenic RBC
      retention in animals.

PMID- 22395808
TI  - Brownian dynamics simulation study on the self-assembly of incompatible star-like
      block copolymers in dilute solution.
AB  - We study the self-assembly of symmetric star-like block copolymers
      (A(x))(y)(B(x))(y)C in dilute solution by using Brownian dynamics simulations. In
      the star-like block copolymer, incompatible A and B components are both
      solvophobic, and connected to the center bead C of the polymer. Therefore, this
      star-like block copolymer can be taken as a representative of soft and deformable
      Janus particles. In our Brownian dynamics simulations, these "soft Janus
      particles" are found to self-assemble into worm-like lamellar structures, loose
      aggregates and so on. By systematically varying solvent conditions and
      temperature, we build up the phase diagram to illustrate the effects of polymer
      structure and temperature on the aggregate structures. At lower temperatures, we
      can observe large worm-like lamellar aggregates. Upon increasing the temperature,
      some block copolymers detach from the aggregate; this phenomenon is especially
      sensitive for the polymers with less arms. The aggregate structure will be quite
      disordered when the temperature is high. The incompatibility between the two
      parts in the star-like block copolymer also affects the self-assembled
      structures. We find that the worm-like structure is longer and narrower as the
      incompatibility between the two parts is stronger.

PMID- 22395809
TI  - Association of LIPA gene polymorphisms with obesity-related metabolic
      complications among severely obese patients.
AB  - The lipase A, lysosomal acid, cholesterol esterase enzyme (LIPA) is involved in
      the hydrolysis of triglycerides (TGs) and cholesteryl esters (CEs) delivered to
      lysosomes. LIPA deficiency in human causes two distinct phenotypes characterized
      by intracellular storage of CE and derangements in the control of cholesterol
      production, namely the Wolman disease (WD) and the CE storage disease (CESD). To
      test the potential association of LIPA gene polymorphisms with obesity-related
      metabolic complications, promoter, exons, and intronic flanking regions of the
      LIPA gene were first sequenced in 25 individuals. From the 14 common
      polymorphisms identified, 12 tagging single-nucleotide polymorphisms (tSNPs) were
      genotyped in a cohort of 1,751 obese individuals. After adjustments for the
      effect of age, sex, diabetes, and medication, the C allele of SNP rs1051338 was
      associated with lower blood pressure (BP; systolic (SBP) P = 0.004; diastolic
      (DBP) P = 0.006). Three of the tested SNPs were associated with modifications of
      the plasma lipid profile. The G/G genotype of rs2071509 was associated with
      higher high-density lipoprotein cholesterol (HDL-C) levels (P = 0.009) and minor
      allele of rs1131706 was also associated with higher HDL-C (P = 0.004) and an
      association between rs3802656 and total cholesterol (total-C)/HDL-C ratio was
      identified (P = 0.04). These results thus suggest that LIPA polymorphisms
      contribute to the interindividual variability observed in obesity-related
      metabolic complications.

PMID- 22395806
TI  - The circadian clock and pathology of the ageing brain.
AB  - Ageing leads to a functional deterioration of many brain systems, including the
      circadian clock--an internal time-keeping system that generates ~24-hour rhythms
      in physiology and behaviour. Numerous clinical studies have established a direct
      correlation between abnormal circadian clock functions and the severity of
      neurodegenerative and sleep disorders. Latest data from experiments in model
      organisms, gene expression studies and clinical trials imply that dysfunctions of
      the circadian clock contribute to ageing and age-associated pathologies, thereby
      suggesting a functional link between the circadian clock and age-associated
      decline of brain functions. Potential molecular mechanisms underlying this link
      include the circadian control of physiological processes such as brain
      metabolism, reactive oxygen species homeostasis, hormone secretion, autophagy and
      stem cell proliferation.

PMID- 22395810
TI  - Residual obesity stigma: an experimental investigation of bias against obese and
      lean targets differing in weight-loss history.
AB  - This study investigated stigma directed at formerly obese persons who lost weight
      and became lean (through behavioral or surgical methods), or lost weight but
      remained obese, relative to weight-stable obese and weight-stable lean persons.
      This study also compared stigma directed at obese persons following exposure to
      descriptions of persons who lost weight vs. remained weight stable. In a between
      subject experimental design, participants (n = 273) were randomly assigned to
      read vignettes describing targets varying across two dimensions, weight stability
      (i.e., weight stable or weight lost) and current weight (i.e., currently obese or
      currently lean). Participants completed measures of stigma against specific
      targets and measures of stigma against obese individuals in general. Lean
      individuals who were formerly obese were stigmatized more on attractiveness than
      weight-stable lean individuals, and as much as currently obese individuals.
      Stigma across domains was greater among currently obese individuals (regardless
      of whether they had lost weight from a higher weight) than among currently lean
      individuals. After reading vignettes describing weight loss, participants
      demonstrated greater obesity stigma than after reading vignettes describing
      weight-stable individuals. These results suggest that residual stigma remains
      against people who have previously been obese, even when they have lost
      substantial amounts of weight and regardless of their weight-loss method.
      Exposure to portrayals of the malleability of body weight, such as those promoted
      in the popular media, may significantly worsen obesity stigma.

PMID- 22395811
TI  - Single slice vs. volumetric MR assessment of visceral adipose tissue: reliability
      and validity among the overweight and obese.
AB  - Visceral adipose tissue (VAT) is associated with abnormal cardiovascular and
      metabolic profiles. Total VAT volume of the abdominal compartment by magnetic
      resonance imaging (MRI) is the gold-standard measurement for VAT but is costly
      and time consuming. Prior studies suggest VAT area on a single slice MR image may
      serve as a surrogate for total VAT volume but it is unknown if this relationship
      is maintained in overweight and obese men and women. Untreated sleep apnea
      subjects enrolled into the Icelandic Sleep Apnea Cohort (ISAC) underwent
      abdominal MRI. VAT area and subcutaneous adipose tissue (SAT) area at the L2-L3
      and L4-L5 interspaces and total VAT and SAT volumes were determined by manual
      examination using image analysis software; 539 men and 129 women with mean ages
      of 54.1 and 58.8 years and mean BMI of 32.2 kg/m(2) and 33.7 kg/m(2),
      respectively, were studied. Mean total VAT volume was 40% smaller and mean total
      SAT was 25% larger among females compared with males. The correlation with VAT
      volume was significantly larger for L2-L3 VAT area (r = 0.96) compared to L4-L5
      VAT area (r = 0.83). The difference in correlation coefficients was statistically
      significant (nonparametric bootstrap P < 0.001 with 95% confidence interval (CI)
      for the difference from 0.11 to 0.15. VAT area at L2-L3 was also significantly
      better correlated with VAT volume than traditional anthropometric variables.
      Linear regression analyses demonstrated that L2-L3 area alone was sufficient for
      predicting total VAT volume and that the nature of the linear association was
      maintained across all levels of obesity and in both genders.

PMID- 22395813
TI  - Bulk- and surface-modified combinable PDMS capillary sensor array as an easy-to
      use sensing device with enhanced sensitivity to elevated concentrations of
      multiple serum sample components.
AB  - To enhance sensitivity and facilitate easy sample introduction into a combinable
      poly(dimethylsiloxane) (PDMS) capillary (CPC) sensor array, PDMS was modified in
      bulk and on its surface to prepare "black" PDMS coated with a silver layer and
      self-assembled monolayer (SAM). India ink, a traditional Japanese black ink, was
      added to the PDMS pre-polymer for bulk modification. The surface was modified by
      a silver mirror reaction followed by SAM formation using cysteine. These
      modifications enhanced the fluorescence signals by reflecting them from the
      surface and reducing background interference. A decrease in the water contact
      angle led to enhanced sensitivity and easy sample introduction. Furthermore, a
      CPC sensor array for multiplex detection of serum sample components was prepared
      that could quantify the analytes glucose, potassium, and alkaline phosphatase
      (ALP). When serum samples were introduced by capillary action, the CPC sensor
      array showed fluorescence responses for each analyte and successfully identified
      the components with elevated concentrations in the serum samples.

PMID- 22395812
TI  - B lymphocytes in human subcutaneous adipose crown-like structures.
AB  - Accumulation of macrophages and T cells within crown-like structures (CLS) in
      subcutaneous adipose tissue predicts disease severity in obesity-related insulin
      resistance (OIR). Although rodent data suggest the B cell is an important feature
      of these lesions, B cells have not been described within the human CLS. In order
      to identify B cells in the human subcutaneous CLS (sCLS) in obese subjects and
      determine whether the presence of B cells predict insulin resistance, we examined
      archived samples of subcutaneous and omental fat from 32 obese men and women and
      related findings to clinical parameters. Using immunohistochemistry, we
      identified B (CD19(+)) and T cells (CD3 (+)) within the sCLS and perivascular
      space. The presence and density of B cells (B cells per high-power field (pHPF),
      T cells pHPF, and B cell:T cell (B:T) ratio) were compared with measures of
      insulin resistance (homeostasis model assessment (HOMA)) and other variables. In
      16 of 32 subjects (50%) CD19(+) B cells were localized within sCLS and were
      relatively more numerous than T cells. HOMA was not different between subjects
      with CD19(+) vs. CD19(-) sCLS (5.5 vs. 5.3, P = 0.88). After controlling for
      diabetes and glycemia (hemoglobin A(1c) (HbA(1c))), the B:T ratio correlated with
      current metformin treatment (r = 0.89, P = 0.001). These results indicate that in
      human OIR, B cells are an integral component of organized inflammation in
      subcutaneous fat, and defining their role will lead to a better understanding of
      OIR pathogenesis and potentially impact treatment.

PMID- 22395815
TI  - Preparation and electrochemistry of Pd-Ni/Si nanowire nanocomposite catalytic
      anode for direct ethanol fuel cell.
AB  - A new silicon-based anode suitable for direct ethanol fuel cells (DEFCs) is
      described. Pd-Ni nanoparticles are coated on Si nanowires (SiNWs) by electroless
      co-plating to form the catalytic materials. The electrocatalytic properties of
      the SiNWs and ethanol oxidation on the Pd-Ni catalyst (Pd-Ni/SiNWs) are
      investigated electrochemically. The effects of temperature and working potential
      limit in the anodic direction on ethanol oxidation are studied by cyclic
      voltammetry. The Pd-Ni/SiNWs electrode exhibits higher electrocatalytic activity
      and better long-term stability in an alkaline solution. It also yields a larger
      current density and negative onset potential thus boding well for its application
      to fuel cells.

PMID- 22395814
TI  - LIME mediates immunological synapse formation through activation of VAV.
AB  - Lck Interacting Membrane protein (LIME) was previously characterized as a
      transmembrane adaptor protein mediating TCR-dependent T cell activation. Here, we
      show that LIME associates with Vav in response to TCR stimulation and is required
      for Vav guanine nucleotide exchange factor (GEF) activity for Rac1. Consistent
      with this finding, actin polymerization at the immunological synapse (IS) was
      markedly enhanced by overexpression of LIME, but was reduced by expression of a
      LIME shRNA. Moreover, TCR-mediated cell adhesion to ICAM-1, laminin, or
      fibronectin was downregulated by expression of LIME shRNA. In addition, in the
      IS, LIME but not LAT was found to localize at the peripheral-supramolecular
      activation cluster (p-SMAC) where the integrins were previously shown to be
      localized. Together, these results establish LIME as a transmembrane adaptor
      protein linking TCR stimulation to IS formation and integrin activation through
      activation of Vav.

PMID- 22395816
TI  - Management of chronic myeloid leukemia in childhood.
AB  - Childhood chronic myelogenous leukemia (CML) is a rare malignancy, and experience
      with optimal treatment is very limited. Traditionally, allogeneic hematopoietic
      stem cell transplantation was considered the only curative treatment. Imatinib, a
      small-molecule inhibitor of the BCR-ABL tyrosine kinase (TKI), has been proven
      highly successful in adults with CML, resulting in prolonged molecular response
      with limited drug toxicity. This drug is now included as front-line therapy for
      CML in pediatrics as well, though valid concerns about serious late sequelae
      remain unresolved. Specific pediatric treatment guidelines have not yet been
      formulated, and most algorithms are derived from experience in adult CML. This
      overview attempts to summarize pediatric studies on issues such as dose,
      duration, adverse effects, and steering criteria for TKI treatment, adapting
      guidelines developed in adult medicine to pediatrics. Most importantly, pediatric
      patients with CML receiving TKI treatment should be enrolled into formal trials.

PMID- 22395818
TI  - Self-reported body weight and height: an assessment tool for identifying children
      with overweight/obesity status and cardiometabolic risk factors clustering.
AB  - Body mass index (BMI) is commonly used for assessing body fat. Self-reported body
      weight and height derived BMI (SRDBMI) is a simple, low cost and non-invasive
      assessment tool and it may be a useful self-reported assessment tool to monitor
      the prevalence of overweight/obesity in community settings and for
      epidemiological research. We assessed the agreement of BW and BH between assessor
      measured and child self-reported values and evaluated the diagnostic ability of
      SRDBMI to identify children with overweight/obesity status and cardiometabolic
      risk factors (CMRFs) clustering. A cross-sectional study was conducted in school
      settings using a cluster sampling method. A total of 1,614 children aged 6-18
      years were included in the analysis. Children were given a questionnaire to
      complete at home prior to the anthropometric measurements and blood taking at the
      schools. There was almost perfect agreement on BW, BH and BMI between self
      reported and measured values [intraclass correlation coefficients ranged from
      0.93 (95% CI: 0.93-0.94) to 0.99 (95% CI: 0.98-0.99)]. About half of the children
      reported their BW and BH absolute values within 1 kg and 2 cm of measured values,
      respectively. The SRDBMI demonstrated good diagnostic ability for identifying
      children with overweight/obesity status (sensitivity, specificity, positive and
      negative predictive values ranged from 0.83 to 0.98) and CMRFs clustering (AUC
      ROCs values of BMI between measured and self-reported values were close ranging
      from 0.85 to 0.89). Self-reported BW and BH demonstrated almost perfect agreement
      with measured values and could substantially identify children with
      overweight/obesity status and CMRFs clustering.

PMID- 22395817
TI  - Patterns of body composition among HIV-infected, pregnant Malawians and the
      effects of famine season.
AB  - We describe change in weight, midupper arm circumference (MUAC), arm muscle area
      (AMA) and arm fat area (AFA) in 1130 pregnant HIV-infected women with CD4 counts
      > 200 as part of the BAN Study ( www.thebanstudy.org ), a randomized, controlled
      clinical trial to evaluate antiretroviral and nutrition interventions to reduce
      mother-to-child transmission of HIV during breast feeding. In a longitudinal
      analysis, we found a linear increase in weight with a mean rate of weight gain of
      0.27 kgs/week, from baseline (12 to 30 weeks gestation) until the last follow-up
      visit (32-38 weeks). Analysis of weight gain showed that 17.1% of the intervals
      between visits resulted in a weight loss. In unadjusted models, MUAC and AMA
      increased and AFA declined during late pregnancy. Based on multivariable
      regression analysis, exposure to the famine season resulted in larger losses in
      AMA [-0.08, 95% CI -0.14, -0.02; p = 0.01] while AFA losses occurred irrespective
      of season [-0.55, 95%: -0.95, -0.14, p = 0.01]. CD4 was associated with AFA
      [0.21, 95% CI 0.01, 0.41, p = .04]. Age was positively associated with MUAC and
      AMA. Wealth was positively associated with MUAC, AFA, and weight. While patterns
      of anthropometric measures among HIV-infected, pregnant women were found to be
      similar to those reported for uninfected women in sub-Saharan Africa, effects of
      the famine season among undernourished, Malawian women are of concern. Strategies
      to optimize nutrition during pregnancy for these women appear warranted.

PMID- 22395819
TI  - Sugar uptake analysis of suspension Arabidopsis, tobacco, and rice cells in
      various media using an FT-IR/ATR method.
AB  - The kinetic behavior of the sugar uptake phenomena of a suspension of Arabidopsis
      cells was investigated by mid-infrared spectroscopy using Fourier transform
      infrared spectrometers and attenuated total reflection techniques. The kinetic
      behavior of the cell growth was also studied and the growth and the sugar uptake
      behaviors were discussed for three typical plant cells (Arabidopsis, TBY-2, and
      rice cells). The cell growth rate and the lag period were influenced by not only
      the types of the plant cells, but also the sugar species used as the carbon
      source. The characteristics of the sugar uptake behavior were clarified based on
      the difference in the three types of plant cells. The cell growth and the sugar
      uptake progressed at approximately the same time in the TBY-2 cells. In the rice
      cells, the sugar uptake rate was relatively lower than that of the others. On the
      other hand, the sugar uptake of the Arabidopsis cells started before the cell
      growth. Furthermore, glucose as the carbon source of the Arabidopsis cell
      cultivation seems to significantly influence the sugar metabolism. Glucose had a
      significant influence on the sugar metabolism of the other sugar under the
      conditions for the mixture of glucose and the other sugar. The characteristics of
      the sugar uptake phenomena based on the cell growth stage was typical for each
      plant cell except for some sugars, such as galactose and trehalose, and the
      behavior of the total sugar uptake had not changed. These results suggested that
      the cell growth and the sugar uptake in the plant cell cultivation processes may
      be controlled by the combined supply of the sugar species as the carbon source.
      The detailed data for plant cell cultivation using each sugar obtained in this
      study would be useful for bioscience research and for cultivation process control
      using various sugars, for example, purified or sugar mixtures formed from biomass
      materials.

PMID- 22395820
TI  - Convergent and discriminant validity and reliability of the pediatric anxiety
      rating scale in youth with autism spectrum disorders.
AB  - The psychometric properties of the Pediatric Anxiety Rating Scale (PARS), a
      clinician-administered measure for assessing severity of anxiety symptoms, were
      examined in 72 children and adolescents diagnosed with an autism spectrum
      disorder (ASD). The internal consistency of the PARS was 0.59, suggesting that
      the items were related but not repetitive. The PARS showed high 26-day test
      retest (ICC = 0.83) and inter-rater reliability (ICC = 0.86). The PARS was
      strongly correlated with clinician-ratings of overall anxiety severity and parent
      report anxiety measures, supporting convergent validity. Results for divergent
      validity were mixed. Although the PARS was not associated with the sum of the
      Social and Communication items on the Autism Diagnostic Observation System, it
      was moderately correlated with parent-reported inattention, aggression and
      externalizing behavior. Overall, these results suggest that the psychometric
      properties of the PARS are adequate for assessing anxiety symptoms in youth with
      ASD, although additional clarification of divergent validity is needed.

PMID- 22395821
TI  - A meta-analysis of the diagnostic test accuracy of MRA and MRI for the detection
      of glenoid labral injury.
AB  - PURPOSE: Magnetic resonance imaging (MRI) and magnetic resonance arthrography
      (MRA) have gained increasing favour in the assessment of patients with suspected
      glenoid labral injuries. The purpose of this study was to determine the
      diagnostic accuracy of MRI or MRA in the detection of gleniod labral lesions.
      MATERIALS AND METHODS: A systematic review was undertaken of the electronic
      databases Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED
      and CINAHL, in addition to a search of unpublished literature databases. All
      studies which compared the ability of MRI or MRA (index test) to assess gleniod
      labral tears or lesions, when verified with a surgical procedure (arthroscopy or
      open surgery-reference test) were included. Data extraction and methodological
      appraisal using the QUADAS tool were both conducted by two reviewers
      independently. Data were analysed through a summary receiver operator
      characteristic curve and pooled sensitivity and specificity analysis were
      calculated with 95% confidence intervals. RESULTS: Sixty studies including 4,667
      shoulders from 4,574 patients were reviewed. There appeared slightly greater
      diagnostic test accuracy for MRA over MRI for the detection of overall gleniod
      labral lesions (MRA-sensitivity 88%, specificity 93% vs. MRI sensitivity 76% vs.
      specificity 87%). Methodologically, studies recruited and identified their
      samples appropriately and clearly defined the radiological procedures. In
      general, it was not clearly defined why patients were lost during the study, and
      studies were poor at recording whether the same clinical data were available to
      the radiologist interpreting the MRI or MRA as would be available in clinical
      practice. Most studies did not state whether the surgeon interpreting the
      arthroscopic procedure was blinded to the results of the MR or MRA imaging.
      CONCLUSIONS: Based on the available literature, overall MRA appeared marginally
      superior to MRI for the detection of glenohumeral labral lesions. LEVEL OF
      EVIDENCE: Level 2a.

PMID- 22395822
TI  - Augmentative locking compression plate fixation for the management of long bone
      nonunion after intramedullary nailing.
AB  - OBJECTIVE: Intramedullary nailing is widely used in the treatment of long bone
      fractures. But some patients suffer from nonunion after receiving intramedullary
      nailing. This paper investigates the methods and effects of locking compression
      plate (LCP) in the treatment of long bone nonunion after intramedullary nailing.
      METHODS: A total of 6 patients (4 males, 2 females) with long bone nonunion were
      enrolled. All these patients had previously undergone intramedullary nailing for
      fractures of long bones (4 femurs, 2 tibiae). The average time from injury to LCP
      treatment was 12.2 months. The locking compression plate was applied over the
      intramedullary nail, and unicortical purchase achieved with locking head screws
      due to underlying nails. Autologous bone grafting was done in all cases. RESULTS:
      Six patients were followed up for 12-20 months (mean 14.2 months). X-ray imaging
      showed bone callus at the broken ends of the fracture at 3-7 (mean 4.5) months
      after surgery. All patients did not have any complications such as infection,
      breaking or loosening of the LCPs. CONCLUSION: LCP can be used for the treatment
      of long bone nonunion after intramedullary nailing for its convenience, minimal
      invasion and curative effect.

PMID- 22395824
TI  - Continuous spinal anesthesia for Cesarean hysterectomy and massive hemorrhage in
      a parturient with placenta increta.
AB  - PURPOSE: We present anesthetic management using a continuous spinal anesthesia
      (CSA) technique in a patient with placenta increta who underwent elective
      Cesarean hysterectomy with massive postpartum hemorrhage. CLINICAL FEATURES: A 34
      yr-old parturient (G3P2) was scheduled for Cesarean delivery and possible
      hysterectomy at 35(+3) weeks due to suspected placenta accreta. Her body mass
      index was 21 kg.m(-2) and she had a reassuring airway. Inadvertent dural puncture
      occurred during combined spinal-epidural (CSE) placement, and a decision was made
      to thread the epidural catheter and utilize a CSA technique. Following delivery
      of a healthy infant, morbid adherence of the placenta to the myometrium was
      confirmed, and a supracervical hysterectomy was performed. Eight litres of blood
      loss occurred postpartum requiring resuscitation with crystalloid 3,800 mL,
      colloid 1,500 mL, red blood cells 16 units, fresh frozen plasma 16 units,
      platelets 4 units, and cryoprecipitate 1 unit. The patient developed pulmonary
      edema requiring conversion to general anesthesia. The patient's cardiovascular
      status was stable throughout surgery, and her lungs were mechanically ventilated
      for 18 hr postoperatively in the intensive care unit. The intrathecal catheter
      was removed 24 hr after placement. She developed no adverse neurological sequelae
      and reported no postdural puncture headache. The pathology report confirmed
      placenta increta. CONCLUSION: A CSA technique may be a viable option in the event
      of inadvertent dural puncture during planned CSE or epidural placement in
      patients with a reassuring airway undergoing Cesarean delivery. Although a
      catheter-based neuraxial technique is appropriate for Cesarean hysterectomy for
      abnormal placentation, conversion to general anesthesia may be required in the
      event of massive perioperative hemorrhage and fluid resuscitation.

PMID- 22395823
TI  - Molecular evolution of a malaria resistance gene (DARC) in primates.
AB  - Genes involved in host-pathogen interactions are often strongly affected by
      positive natural selection. The Duffy antigen, coded by the Duffy antigen
      receptor for chemokines (DARC) gene, serves as a receptor for Plasmodium vivax in
      humans and for Plasmodium knowlesi in some nonhuman primates. In the majority of
      sub-Saharan Africans, a nucleic acid variant in GATA-1 of the gene promoter is
      responsible for the nonexpression of the Duffy antigen on red blood cells and
      consequently resistance to invasion by P. vivax. The Duffy antigen also acts as a
      receptor for chemokines and is expressed in red blood cells and many other
      tissues of the body. Because of this dual role, we sequenced a ~3,000-bp region
      encompassing the entire DARC gene as well as part of its 5' and 3' flanking
      regions in a phylogenetic sample of primates and used statistical methods to
      evaluate the nature of selection pressures acting on the gene during its
      evolution. We analyzed both coding and regulatory regions of the DARC gene. The
      regulatory analysis showed accelerated rates of substitution at several sites
      near known motifs. Our tests of positive selection in the coding region using
      maximum likelihood by branch sites and maximum likelihood by codon sites did not
      yield statistically significant evidence for the action of positive selection.
      However, the maximum likelihood test in which the gene was subdivided into
      different structural regions showed that the known binding region for P. vivax/P.
      knowlesi is under very different selective pressures than the remainder of the
      gene. In fact, most of the gene appears to be under strong purifying selection,
      but this is not evident in the binding region. We suggest that the binding region
      is under the influence of two opposing selective pressures, positive selection
      possibly exerted by the parasite and purifying selection exerted by chemokines.

PMID- 22395825
TI  - Ultrasound-guided vascular access: the importance of the needle bevel.

PMID- 22395826
TI  - Correct positioning of double-lumen tubes.

PMID- 22395827
TI  - Venoarterial extracorporeal membrane oxygenation support for two patients after
      pulmonary thromboendarterectomy.

PMID- 22395828
TI  - Bladder involvement in Behcet's disease.
AB  - PURPOSE: To review different aspects of the bladder involvement in Behcet's
      disease as a rare complication. MATERIALS AND METHODS: We searched PubMed, Ovid,
      and Google Scholar for Behcet's and neuro-Behcet's disease and neurogenic and
      neuropathic bladder, bladder involvement, voiding dysfunction, and urologic
      manifestations. Fourteen full-texts and one abstract were retrieved. RESULTS:
      Most involved patients are young to middle-aged men. Both bladder filling and
      emptying problems can be seen, with the storage symptoms being the most common
      finding. Sphincter function could be normal, dyssynergic, or deficient. The most
      common urodynamic finding is detrusor overactivity. In cystoscopic examination,
      ulcers or nodules due to vasculitis can be seen, which along with neurologic
      causes give rise to the voiding symptoms. The rate of cancers does not increase
      in Behcet's disease. Surgery and chemotherapy are tolerated well. However,
      radiotherapy may be associated with increased complication rates. CONCLUSION:
      Treatment plan should be tailored according to the specific type of the bladder
      involvement. Periodic re-evaluation is required because of the changing nature of
      the bladder behavior.

PMID- 22395829
TI  - Tuberculous epididymo-orchitis: MRI appearance.

PMID- 22395830
TI  - Bilateral giant renal cysts masquerading as malignant ascites.

PMID- 22395831
TI  - Mini-laparoscopic donor nephrectomy: a novel technique.
AB  - PURPOSE: To describe mini-laparoscopic donor nephrectomy (MLDN). In this novel
      approach, we used 3.5 mm trocars in usually visible parts of the abdomen.
      MATERIALS AND METHODS: A 27-year-old man underwent MLDN. The first trocar was
      placed transumblically, which is used for videoscope. Two 3.5 mm trocars were
      placed above and lateral to the umbilicus and were used for grasping and
      scissoring. A 10-mm trocar was placed through fascia within pfannenstiel
      incision, which is also used for the kidney extraction. The site of this trocar
      will be covered later by hair growth. This trocar is used for vascular clipping.
      RESULTS: Mini-laparoscopic donor nephrectomy was done successfully. Operation
      time was 135 minutes and warm ischemia time was 5 minutes. Patient was discharged
      from the hospital in 36 hours. No peri-operative complication occurred. Nadir
      serum level of creatinine in the recipient was 0.8 mg/dL. CONCLUSION: Mini
      laparoscopic donor nephrectomy can be a good alternative to standard laparoscopic
      donor nephrectomy, giving an excellent cosmetic result. This technique is more
      ergonomic and user-friendly compared to laparoendoscopic single-site surgery
      (LESS) techniques.

PMID- 22395832
TI  - Prevalence and management of complications of ureteroscopy: a seven-year
      experience with introduction of a new maneuver to prevent ureteral avulsion.
AB  - PURPOSE: To evaluate the prevalence and type of rigid ureteroscopy complications
      and suggest a new method for ureteral avulsion prevention. MATERIALS AND METHODS:
      Between March 2002 and March 2009, we retrospectively evaluated 2955 patients who
      had undergone diagnostic or therapeutic ureteroscopy for asymptomatic hematuria,
      migrated ureteral stent, or transurethral lithotripsy. They were enrolled from
      four hospitals in Ahvaz, Iran. RESULTS: Complications were encountered in 241
      (8%) patients, including transient hematuria (4.2%), mucosal erosion (1.4%),
      stone migration (1.3%), ureteral perforation (1.2%), and fever and/or sepsis
      (1.0%). Ureteral avulsion occurred in 6 (0.2%) patients. Mostly, complications
      were managed conservatively, using ureteral stenting. Ureteral avulsions were
      managed using a new technique. CONCLUSION: In our series, the complication rate
      is comparable with the literature. A new technique was used in case of
      ureteroscope entrapment in the ureter, to lessen the occurrence of ureteral
      avulsion.

PMID- 22395833
TI  - Therapeutic effects of aqueous extracts of Petroselinum sativum on ethylene
      glycol-induced kidney calculi in rats.
AB  - PURPOSE: To investigate the therapeutic effects of the aqueous extract of
      Petroselinum Sativum aerial parts and roots on kidney calculi. MATERIALS AND
      METHODS: Thirty-six male Wistar rats were randomly assigned into 6 groups and
      treated for 30 days. Group A served as normal control and group B received 1%
      ethylene glycol in drinking water. Groups C, D, E, and F received 1% ethylene
      glycol from day 0 and were used as the treatment subjects. Rats in groups C and D
      received 200 and 600 mg/kg body weight of aerial parts aqueous extract,
      respectively, and those in groups E and F received 200 and 600 mg/kg body weight
      of root aqueous extract in drinking water, respectively, from the 14th day of the
      experiment. RESULTS: On the 14th and 30th days of the experiment, serum level of
      magnesium (1.71 +/- 0.12 and 3.81 +/- 0.25, respectively) decreased significantly
      while serum level of calcium (10.45 +/- 0.26 and 11.33 +/- 0.18, respectively)
      increased significantly in group B compared with the control group (14th day:
      magnesium = 2.87 +/- 0.17 and calcium = 8.80 +/- 0.00 and 30th day: magnesium =
      6.01 +/- 0.00 and calcium = 8.30 +/- 0.22; P < .001). In the treatment groups of
      C, D, E, and F, the number of deposits decreased significantly compared with
      group B on the 30th day (P < .001). The weight of the kidneys increased
      significantly in group B (2.01 +/- 0.17) compared with the control group (1.52 +/
      0.07) and decreased significantly in treatment groups (P < .05). CONCLUSION:
      Petroselinum Sativum has a therapeutic effect on calcium oxalate stones in rats
      with nephrolithiasis and reduces the number of calcium oxalate deposits.

PMID- 22395834
TI  - Detection of recurrent bladder cancer: NMP22 test or urine cytology?
AB  - PURPOSE: To assess the accuracy of voided urine cytology versus urinary nuclear
      matrix protein 22 (NMP22) qualitative assay in the diagnosis of various grades
      and stages of recurrent bladder transitional cell carcinoma (TCC). MATERIALS AND
      METHODS: From July 2007 to February 2009, all patients with history of
      superficial bladder TCC were included in this multi-center study. Each patient
      provided three serial voided urine samples for cytologic examination and one
      sample for the NMP22 qualitative assay prior to urethrocystoscopy. The
      sensitivity and specificity of urine cytology and the NMP22 test were determined.
      RESULTS: The sensitivities of the NMP22 test and cytology for detection of
      recurrence were 78.8% and 44.2%, respectively (P = .001), while the specificities
      were 69.6% and 83.7%, respectively (P = .019). The NMP22 test showed
      significantly higher sensitivity than cytology in detecting recurrences in low
      risk and intermediate-risk groups. CONCLUSION: The NMP22 assay could be used for
      detection of superficial bladder cancer, especially in low- and intermediate-risk
      groups; however, the value of the test is limited by its low specificity.

PMID- 22395835
TI  - Renal tumors in young adults: a single-center experience from a developing
      country.
AB  - PURPOSE: To determine the pattern and outcome of renal tumors in young adults in
      a large surgical series in Pakistan. MATERIALS AND METHODS: We retrospectively
      analyzed 133 young adults (age: >= 16 to <= 40 years) with 136 renal tumors, who
      underwent surgical treatment for suspected renal cancer from 1994 till 2010. The
      clinical and pathological parameters were determined and their impact on final
      outcome was analyzed. RESULTS: The mean age of the patients was 33.3 +/- 6.2
      years. Of 136, 121 (88.9%) renal tumors were malignant and 15 (11%) were benign.
      Among malignancies, 76 (62.7%) patients had stage I or II tumors, 22 (18.1%)
      stage III, and 23 (19%) stage IV at surgery. The overall cancer-specific survival
      for malignant tumors at 1, 5, and 10 years was 97%, 83%, and 83%, whereas the
      cancer-free survival (CFS) was 80%, 63%, and 37%, respectively. Patients with age
      <= 35 years had 1 and 5-year CFS of 83% and 71%, respectively, as compared with
      76% and 49% for patients > 35 years (P = .02; odds ratio = 2.3; P = .03).
      Regarding tumor size, 1 and 5-year CFS for tumors <= 10 cm was 93% and 75%, while
      tumors > 10 cm showed CFS of 56% and 41%, respectively (P = .0001; odds ratio =
      4.2; P = .0001). For stage I tumors, CFS at 1 and 5 years was 98% and 84%; for
      stage II, 82% and 63%; and for stage III, 62% and 50%,respectively. One-year
      survival for stage IV was 48% only (P = .0001). CONCLUSION: A wide heterogeneity
      of renal tumors is seen in young adults with delayed presentation.

PMID- 22395836
TI  - Expression of Bcl-2 and Bax in advanced or metastatic prostate carcinoma.
AB  - PURPOSE: To evaluate the correlation of Bcl-2 and Bax protein expressions with
      biochemical failure-free survival in patients with advanced or metastatic
      prostate carcinoma (PCa) undergoing androgen deprivation therapy. MATERIALS AND
      METHODS: This retrospective study was performed on patients with locally advanced
      (>= T3) or metastatic PCa, who were referred to Omid Hospital between years 2003
      and 2007. All subjects had undergone androgen deprivation therapy. Samples were
      analyzed immunohistochemically for Bax and Bcl-2 expression. The H-score was
      calculated for each sample based on intensity and percentage of stained cells. H
      score > 50 was considered positive. RESULTS: Thirty-seven patients (13 metastatic
      and 24 locally advanced) were eligible for analysis. Thirty-six (97.3%) samples
      were positive for Bax and 26 (70.3%) for Bcl-2 expression. The median H-score for
      Bax and Bcl-2 was 200 (range, 40 to 300) and 85 (range, 0 to 220), respectively.
      While there was no correlation between Bax expression and Gleason score, high Bcl
      2 expression (H-score > 85) was significantly associated with Gleason score > 7
      (P = .004). The median time to progression in the advanced and metastatic groups
      was 22 (range, 10 to 37) months and 16 (range, 9 to 26) months, respectively.
      High Bcl-2 expression (P = .01) and prostate-specific antigen > 20 ng/mL (P =
      .01) were significant predictors of lower biochemical progression-free survival.
      CONCLUSION: High Bcl-2 expression was associated with higher Gleason scores and
      lower biochemical-free survival in patients with advanced PCa undergoing androgen
      deprivation therapy.

PMID- 22395837
TI  - Effect of low dose dopamine on early graft function in living unrelated kidney
      donors.
AB  - PURPOSE: To evaluate the effect of low-dose dopamine administration on the early
      function of the kidney in unrelated kidney donors after transplantation.
      MATERIALS AND METHODS: In this double-blinded clinical trial, 60 adult kidney
      donors and 60 recipients, younger than 50 years old, were studied. Donors and
      recipients were randomly divided into two groups; group 1 received dopamine 3
      u/kg/min and group 2 received similar regimen of placebo. During the first 3 days
      postoperatively, serum levels of urea and creatinine as well as urine output and
      early kidney function were compared between two groups. RESULTS: Serum levels of
      creatinine and urea and urine output during the first three days after the
      operation did not differ statistically significantly between two groups (P =
      .549, P = .306, and P = .375, respectively). Early kidney function was better
      significantly in group 1 (5.3 +/- 3.2 versus 8.6 +/- 8.0 hours; P = .048).
      CONCLUSION: Premedication of the kidney transplant donors with low-dose dopamine
      accelerates early kidney function after transplantation, but has no effect on the
      hemodynamic status and serum levels of creatinine and urea in the donors.

PMID- 22395838
TI  - MRI in stress urinary incontinence: endovaginal MRI with an intracavitary coil
      and dynamic pelvic MRI.
AB  - PURPOSE: To evaluate both morphology of the urethra and its supporting structures
      using endovaginal magnetic resonance imaging (EV-MRI) and the grade of the
      bladder neck prolapsus using dynamic pelvic MRI (DP-MRI) in women with stress
      urinary incontinence (SUI). MATERIALS AND METHODS: We compared 25 women with SUI
      and 8 controls according to the different layers of the urethra, the degree of
      distortion in the periurethral, paraurethral, and pubourethral ligaments, the
      vesicourethral angle, the retropubic space, and the thickness of the puborectal
      muscle. The SUI group was also evaluated according to the number of deliveries
      and degree of the bladder neck prolapsus. RESULTS: Significant differences were
      found in the thickness of each three layers of the urethra between the two groups
      (P < .05). There was a significantly higher pubourethral ligament distortion (P =
      .024) and larger vesicourethral angle (P = .000) in women with SUI. In women with
      SUI, there was no significant relationship between the number of deliveries and
      the degree of the bladder neck prolapsus (P > .05). CONCLUSION: The combined
      usage of the EV-MRI and DP-MRI can provide complementary information concerning
      certain structural abnormalities with specific dysfunction, such as
      vesicourethral angle increase and pubourethral ligament distortion in patients
      with SUI.

PMID- 22395839
TI  - The role of hypothyroidism in male infertility and erectile dysfunction.
AB  - PURPOSE: To evaluate the effect of hypothyroidism on erectile function and sperm
      parameters. MATERIALS AND METHODS: This study was conducted on 24 patients with
      hypothyroidism and 66 normal individuals. Serum levels of hormones, including
      thyroid stimulating hormone (TSH), thyroxin (T4), follicle-stimulating hormone
      (FSH), luteinizing hormone (LH), prolactin (PRL), and testosterone, were measured
      and semen analysis was done in all the participants. Erectile function was
      evaluated using International Index of Erectile Function (IIEF-5) questionnaire.
      RESULTS: The mean IIEF-5 total score was 11.75 [95% confidence interval (CI):
      9.70 to 13.79) and 20.81 (95% CI: 20.02 to 21.6) for hypothyroid group and normal
      subjects, respectively (P = .005). Furthermore, serum concentrations of PRL and
      seminal parameters were significantly different between two groups (P < .001).
      CONCLUSION: Hypothyroidism adversely affects erectile function and sperm
      parameters, including sperm count, morphology, and motility. In patients with
      sperm abnormalities and erectile dysfunction, measurement of thyroid hormones is
      recommended.

PMID- 22395840
TI  - Bladder tissue engineering using biocompatible nanofibrous electrospun
      constructs: feasibility and safety investigation.
AB  - PURPOSE: To investigate the feasibility and safety of using biocompatible,
      nanofibrous electrospun polycaprolactone (PCL) and combination of polylactic acid
      (PLLA) and PCL mats in a canine model. MATERIALS AND METHODS: Plasma-treated
      electrospun unseeded mats were implanted in three dogs. The first dog was
      sacrificed after 3 months and the second and third ones after 4 months, and then,
      the graft was examined macroscopically with subsequent morphological and
      histochemical evaluation. RESULTS: Both films showed high levels of cell
      infiltration and tissue formation, but body response to PLLA/PCL mat in
      comparison to PCL mat was very low. All three implantation models showed the same
      light microscopic morphology, immunohistochemistry, and scanning electron
      microscopy results; nevertheless, only the PCL/PLLA model showed favorable
      clinical results. CONCLUSION: Based on these data, nanofibrous PLLA/PCL
      scaffolding could be a suitable material for the bladder tissue engineering;
      however, it deserves further investigations.

PMID- 22395841
TI  - A new anatomical and surgical landmark in internal abdominal oblique muscle: fat
      triangle.
AB  - PURPOSE: To determine the anatomical landmark within the internal oblique muscle.
      MATERIALS AND METHODS: In a prospective study, the abdominal wall was examined
      for internal oblique muscle land marks in 900 patients undergoing laparatomy.
      RESULTS: There was a fat line at anterior superior iliac spine level to access
      the underlying layers and then to the abdominal cavity. CONCLUSION: A fat
      triangle within the internal oblique muscle provides a suitable region of
      surgical incision at the lower part of the abdominal wall.

PMID- 22395842
TI  - Pediatric sutureless circumcision without using skin closure adhesives: a new
      technique for poor setting.

PMID- 22395843
TI  - Urothelial carcinoma of the ureter in a patient with functional single kidney.

PMID- 22395844
TI  - Urethral foreign body causing urethral fistula.

PMID- 22395845
TI  - Perineal ectopic testis.

PMID- 22395846
TI  - Urethral erosion with recurrent stress incontinence following transobturator tape
      surgery: urethral repair with simultaneous pubovaginal sling.

PMID- 22395847
TI  - Coexistence of cystic nephroma and neuroblastoma: a rare case of a childhood
      collision tumor.

PMID- 22395848
TI  - An unexpected cause of progressive renal failure in a 66-year-old male after
      liver transplantation: secondary hyperoxaluria.
AB  - BACKGROUND: Hyperoxaluria is a rare metabolic disorder characterized by calcium
      oxalate deposition in different tissues. It is caused either by an inherited
      disease of oxalate metabolism [primary hyperoxalurias (PH)] or by an acquired
      disturbance (secondary hyperoxaluria). CASE: We report here an atypical
      presentation of enteric hyperoxaluria-induced renal failure that occurred after
      liver transplantation. Despite adapted treatment and intensive haemodialysis, the
      patient did not recover. This case allows the reviewing of the multiple
      pathophysiological mechanisms involved in this disease. CONCLUSION: Oxalate
      nephropathy should be considered in the differential diagnosis of acute renal
      failure, especially when previous renal impairment and fat malabsorption are
      present. We suggest performing renal biopsy early to allow a prompt diagnosis and
      therapeutic intervention.

PMID- 22395850
TI  - Continuous versus intermittent stochastic resonance whole body vibration and its
      effect on pelvic floor muscle activity.
AB  - AIMS: To determine the optimal stochastic whole body vibration (SR-WBV) load
      modality regarding pelvic floor muscle (PFM) activity in order to complete the SR
      WBV training methodology for future PFM training with SR-WBV. METHODS: The
      continuous and the intermittent SR-WBV modalities were tested by means of
      electromyography in two independent groups (27 women 8 weeks to 1-year postpartum
      and 23 women nulliparae or >1-year postpartum) with self-reported stress urinary
      incontinence. The change in the PFM activity within a single set and over three
      sets were calculated for both SR-WBV modalities together (time effect) and for
      both SR-WBV modalities separately (modality-time interaction). RESULTS: There was
      no statistically significant or clinically relevant change in PFM activity over
      time or PFM fatigue in either SR-WBV modality within one or three sets and no
      difference between the modalities or the groups. CONCLUSIONS: The lack of change
      in PFM activity could be due to a no more than moderate to submaximal PFM
      activity during SR-WBV, the maintenance of reflexive PFM activity despite PFM
      fatigue or a compensation of slow red PFM fiber fatigue by an increase of
      innervation frequency and motor unit recruitment of the fast white fibers. As
      there is no SR-WBV modality dependent difference regarding PFM activity, the
      continuous modality is recommended in clinical practice as it is easier to apply
      and less time consuming.

PMID- 22395849
TI  - Somatic symptoms in traumatized children and adolescents.
AB  - Childhood exposure to trauma has been associated with increased rates of somatic
      symptoms (SS), which may contribute to diminished daily functioning. One hundred
      and sixty-one children residing at a residential treatment home who had
      experienced neglect and/or abuse were administered the Trauma Symptom Checklist
      for Children (TSCC), the Multidimensional Anxiety Scale for Children, and the
      Children's Depression Inventory (CDI). Primary caregivers completed the Child
      Behavior Checklist. Two composite measures of SS were formed to represent both
      child- and caregiver-rated SS. Over 95% of children endorsed at least one SS on
      the child-rated measure. Children who had experienced sexual abuse had higher
      rates of SS relative to children who had not. Child-rated SS were highly
      correlated with the CDI total score and the TSCC subscales of anxiety,
      depression, posttraumatic stress, dissociation, and anger. The TSCC anxiety
      subscale mediated the relationship between sexual abuse and child-rated SS.

PMID- 22395851
TI  - Visual and auditory stimuli associated with swallowing activate mirror neurons: a
      magnetoencephalography study.
AB  - In the present study, we evaluated activated areas of the cerebral cortex with
      regard to the mirror neuron system during swallowing. To identify the activated
      areas, we used magnetoencephalography. Subjects were ten consenting volunteers.
      Swallowing-related stimuli comprised an animated image of the left profile of a
      person swallowing water with laryngeal elevation as a visual swallowing trigger
      stimulus and a swallowing sound as an auditory swallowing trigger stimulus. As
      control stimuli, a still frame image of the left profile without an additional
      trigger was shown, and an artificial sound as a false auditory trigger was
      provided. Triggers were presented at 3,000 ms after the start of image
      presentation. The stimuli were combined and presented and the areas activated
      were identified for each stimulus. With animation and still-frame stimuli, the
      visual association area (Brodmann area (BA) 18) was activated at the start of
      image presentation, while with the swallowing sound and artificial sound stimuli,
      the auditory areas BA 41 and BA 42 were activated at the time of trigger
      presentation. However, with animation stimuli (animation stimulus, animation +
      swallowing sound stimuli, and animation + artificial sound stimuli), activation
      in BA 6 and BA 40, corresponding to mirror neurons, was observed between 620 and
      720 ms before the trigger. Besides, there were also significant differences in
      latency time and peak intensity between animation stimulus and animation +
      swallowing sound stimuli. Our results suggest that mirror neurons are activated
      by swallowing-related visual and auditory stimuli.

PMID- 22395852
TI  - Letter by Daniels regarding article "Silent aspiration risk is volume-dependent".

PMID- 22395854
TI  - Losartan's affinity to fluid bilayers modulates lipid-cholesterol interactions.
AB  - Losartan is an angiotensin II receptor antagonist mainly used for the regulation
      of high blood pressure. Since it was anticipated that losartan reaches the
      receptor site via membrane diffusion, the impact of losartan on model membranes
      has been investigated by small angle X-ray scattering. For this purpose 2-20 mol%
      losartan was incorporated into dimyristoyl-phosphatidylcholine (DMPC) and
      palmitoyl-oleoyl-phosphatidylcholine (POPC) bilayers and into their binary
      mixtures with cholesterol in the concentration range of 0 to 40 mol%. Effects of
      losartan on single component bilayers are alike. Partitioning of losartan into
      the membranes confers a negative charge to the lipid bilayers that causes the
      formation of unilamellar vesicles and a reduction of the bilayer thickness by 3
      4%. Analysis of the structural data resulted in an estimate for the partial area
      of losartan, A(Los) ~ 40 A(2). In the presence of cholesterol, differences
      between the effects of losartan on POPC and DMPC are striking. Membrane
      condensation by cholesterol is retarded by losartan in POPC. This contrasts with
      DMPC, where an increase of the cholesterol content shifts the partitioning
      equilibrium of losartan towards the aqueous phase, such that losartan gets
      depleted from the bilayers from 20 mol% cholesterol onwards. This indicates (i) a
      chain-saturation dependent competition of losartan with lipid-cholesterol
      interactions, and (ii) the insolubility of losartan in the liquid ordered phase
      of PCs. Consequently, losartan's action is more likely to take place in fluid
      plasma membrane patches rather than in domains rich in cholesterol and saturated
      lipid species such as in membrane rafts.

PMID- 22395853
TI  - Synthesis and photophysical evaluation of a pyridinium 4-amino-1,8-naphthalimide
      derivative that upon intercalation displays preference for AT-rich double
      stranded DNA.
AB  - The synthesis, characterisation and solid state crystal structure of a cationic 4
      amino-1,8-naphthalimide derivative (1) are described. The photophysical
      properties of 1 are shown to vary with the solvent polarity and H-bonding
      ability. The fluorescence of 1 is enhanced and blue-shifted in its 1:1 complex
      with 5'-adenosine-monophosphate while it is partially quenched and red-shifted in
      its complex with 5'-guanosine-monophosphate. Linear and circular dichroism
      measurements show that 1 binds to double-stranded DNA by intercalation.
      Comparative UV-visible and fluorescence studies with double stranded synthetic
      polynucleotides poly(dA-dT)(2) and poly(dG-dC)(2) show that 1 binds much more
      strongly to the AT polymer; 1 also has a strong preference for A-T rich sequences
      in natural DNA. Thermal denaturation measurements also reveal a much greater
      stabilisation of the double-stranded poly(dA-dT)(2) than of natural DNA.

PMID- 22395855
TI  - Relationship between the body image and level of pain, functional status,
      severity of depression, and quality of life in patients with fibromyalgia
      syndrome.
AB  - The aims were to investigate how the body image is affected in fibromyalgia
      syndrome (FMS) in comparison to healthy people, as well as to explore the
      relationship of the body image with the level of pain, functional status,
      severity of depression, and quality of life (QoL). Demographic variables,
      symptoms of fibromyalgia, and number of fibromyalgia tender points for 51
      patients with FMS and 41 control subjects were recorded. All patients were asked
      to mark the level of pain on visual analogue scale (VAS). Six-minute walking test
      was recorded for functional assessment. The impact of the disease was evaluated
      by fibromyalgia impact questionnaire (FIQ). All patients were asked to complete
      body image scale (BIS), Beck depression inventory (BDI), and short form-36 (SF
      36). There were no differences between groups with regard to demographic
      variables (p>0.05). Mean VAS was 7.5+/-1.4 for the patients with FMS and 0.3+/
      0.4 for control subjects (p<0.05). Mean FIQ was 70.8+/-13.2 and 8.2+/-9.6 for the
      FMS and control groups, respectively (p<0.05). Mean BIS and BDI were 106.5+/-24.0
      and 20.2+/-11.2 for FMS group and 66.3+/-23.4 and 3.4+/-4.0 for control group,
      respectively (p<0.05). SF-36 subscores were found to be significantly lower in
      patients with FMS than control subjects (p<0.05), except for the social function
      subscore. BIS score had significant relationships both with VAS (r=0.843) and FIQ
      (r=0.290) in patients with FMS (p<0.05). There were significant relationships
      between BIS scores and SF-36 pain (r= -0.288), energy/vitality (r= -0.519),
      mental health (r= -0.442), and general health (r= -0,492) subscores (p<0.05).
      Body image was associated with VAS in the multivariate linear regression
      analysis. The results of the present study indicate that body image is disturbed
      in patients with FMS compared to control subjects. For the evaluation of the
      level of pain, impact of the disease, and QoL in patients with FMS, it would be
      useful to consider the relationship of the body image disturbance with these
      parameters.

PMID- 22395856
TI  - Epidemiology of neuropathic pain and its impact on quality of life.
AB  - Epidemiology is an important clinical tool in designing and evaluating management
      and prevention strategies, and is particularly relevant to neuropathic pain.
      However, there is a relative lack of accurate information available. In one
      sense, neuropathic pain describes a symptom or a mechanism, rather than a
      specific disease; on the other hand, there are sufficient similarities in the
      effects and response to treatment between different causes to make it worthwhile
      to consider neuropathic pain as a distinct condition. However, there are
      important specific disease-based factors that need to be considered separately.
      Estimates of prevalence that are based on specific causes of neuropathic pain
      tend to be lower (1-2%) than those that are based on reports of the classic
      symptoms (6-8%), and further methodological research is needed. All neuropathic
      pain is associated with poor general health, comparable with other severe chronic
      diseases. The importance of newly proposed risk factors, including genetic
      factors, still needs to be assessed at a population level.

PMID- 22395857
TI  - Toxic effects of Carthamus tinctorius L. (Safflower) extract on mouse
      spermatogenesis.
AB  - OBJECTIVE: To evaluate the effects of aqueous extract of Carthamus tinctorius L.,
      also named safflower, on mouse spermatogenesis. METHODS: Sixteen adult male NMRI
      mice were used. Experimental group received Carthamus tinctorius L. extract at
      the dose of 200 mg/kg for 35 consecutive days and control group received only
      distilled water. Testicular histopathology, morphometric analysis and
      spermatogenesis assessments were performed for evaluation of the Carthamus
      tinctorius L. extract effects on testis. RESULTS: Histopathological criteria such
      as epithelial vacuolization, sloughing of germ and detachment were significantly
      decreased in Carthamus tinctorius L. treated mice (p < 0.001). Carthamus
      tinctorius L. extract induced formation of multinucleated giant cells in the
      germinal epithelium. Carthamus tinctorius L. extract also caused a significant
      decrease in seminiferous tubule diameter, seminiferous epithelium height and
      maturation arrest (p < 0.001). CONCLUSION: Carthamus tinctorius L. extract has
      toxic effects on mouse testicular tissue, and recommended to use it with caution
      if there is a reproductive problem.

PMID- 22395858
TI  - 2-Benzoylpyridine thiosemicarbazone as a novel reagent for the single pot
      synthesis of dinuclear Cu(I)-Cu(II) complexes: formation of stable copper(II)
      iodide bonds.
AB  - 2-Benzoylpyridine thiosemicarbazone {R(1)R(2)C(2)=N(2).N(3)H-C(1)(=S)-N(4)H(2),
      R(1) = py-N(1), R(2) = Ph; Hbpytsc} with copper(I) iodide in acetonitrile
      dichloromethane mixture has formed stable Cu(II)-I bonds in a dark green Cu(II)
      iodo-bridged dimer, [Cu(2)(II)(MU-I)(2)(eta(3)-N(1),N(2),S-bpytsc)(2)] 1.
      Copper(I) bromide also formed similar Cu(II)-Br bonds in a dark green Cu(II)
      bromo-bridged dimer, [Cu(2)(II)(MU-Br)(2)(eta(3)-N(1),N(2),S-bpytsc)(2)] 3. The
      formation of dimers 1 and 3 appears to be due to a proton coupled electron
      transfer (PCET) process wherein copper(I) loses an electron to form copper(II),
      and this is accompanied by a loss of -N(3)H proton of Hbpytsc ligand resulting in
      the formation of anionic bpytsc(-). When copper(I) iodide was reacted with
      triphenylphosphine (PPh(3)) in acetonitrile followed by the addition of 2
      benzoylpyridine thiosemicarbazone in dichloromethane (Cu : PPh(3) : Hbpytsc in
      the molar ratio 1:1:1), both Cu(II) dimer 1 and an orange Cu(I) sulfur-bridged
      dimer, [Cu(2)(I)I(2)(MU-S-Hbpytsc)(2)(PPh(3))(2)] 2 were formed. Copper(I)
      bromide with PPh(3) and Hbpytsc also formed Cu(II) dimer 3 and an orange Cu(I)
      sulfur-bridged dimer, [Cu(2)(I)Br(2)(MU-S-Hbpytsc)(2)(PPh(3))(2)] 4. While
      complexes 2 and 4 exist as sulfur-bridged Cu(I) dimers, 1 and 3 are halogen
      bridged. The central Cu(2)S(2) cores of 2 and 4 as well as Cu(2)X(2) of 1 (X = I)
      and 3 (X = Br) are parallelograms. One set of Cu(II)-I and Cu(II)-Br bonds are
      short, while the second set is very long {1, Cu-I, 2.565(1), 3.313(1) A; 3, Cu
      Br, 2.391(1), 3.111(1) A}. The Cu...Cu separations are long in all four complexes
      {1, 4.126(1); 2, 3.857(1); 3, 3.227(1); 4, 3.285(1) A}, more than twice the van
      der Waals radius of a Cu atom, 2.80 A. The pyridyl group appears to be necessary
      for stabilizing the Cu(II)-I bond, as this group can accept pi-electrons from the
      metal.

PMID- 22395859
TI  - Citreorosein inhibits degranulation and leukotriene C4 generation through
      suppression of Syk pathway in mast cells.
AB  - The aim of this study was to evaluate whether citreorosein (CIT), a naturally
      occurring anthraquinone isolated from Polygoni cuspidati (P. cuspidati) radix,
      modulates degranulation and 5-lipoxygenase (5-LO)-dependent leukotriene C(4)
      (LTC(4)) generation in mast cells. Cit suppresses both degranulation and the
      generation of LTC(4) in a dose-dependent manner in stem cell factor (SCF)
      mediated mouse bone marrow-derived mast cells (BMMCs). With regard to its
      molecular mechanism of action, we investigated the effects of CIT on
      intracellular signaling and mast cell activation employing BMMCs. Binding of SCF
      to c-Kit on mast cell membranes induced increases in intrinsic tyrosine kinase
      Syk activity and activation of multiple downstream events including
      phosphorylation of phospholipase Cgamma (PLCgamma), mobilization of intracellular
      Ca(2+), phosphatidylinositol 3-kinase (PI3K), Akt, MAP kinases (MAPKs),
      translocation of phospho-phospholipase A(2) (PLA(2)) and 5-LO. The results from
      the biochemical analysis demonstrate that CIT attenuates degranulation and LTC(4)
      generation through the suppression of multiple step signaling and would be
      beneficial for the prevention of allergic inflammation.

PMID- 22395860
TI  - Pre-eclampsia following chemotherapy for breast cancer during pregnancy: case
      report and review of the literature.
AB  - PURPOSE: There has been some discussion about the effect of antineoplastic agents
      on the trophoblast, and whether this is associated with abnormal placental
      function such as an increased risk of pre-eclampsia/eclampsia. We discuss a
      possible causal relationship between chemotherapy for breast cancer during
      pregnancy and the development of pre-eclampsia based on the occurrence of both in
      a recent pregnancy. METHODS: We report the case of a 34-year-old gravida 4, para
      1 with unilateral ductal invasive breast cancer, treated by surgery and
      subsequent chemotherapy during pregnancy. At 36 + 2 weeks of gestation a growth
      restricted male infant (1,680 g, <5th percentile) was born by urgent caesarean
      section because of acute pre-eclampsia, pathologic CTG and umbilical end
      diastolic reverse flow. This case is reported in detail, and literature and
      databases reviewed. RESULTS: So far there have been no reports suggesting an
      increased risk of pre-eclampsia following chemotherapy for breast cancer in
      pregnancy from the second trimester onwards, and the most probable is an
      accidental occurrence from pre-eclampsia and chemotherapy. CONCLUSIONS: Whenever
      possible, pregnant patients with breast cancer should receive the same treatment
      as those who are not pregnant. Should chemotherapy for breast cancer be indicated
      in pregnancy from the second trimester onwards only, contraindications would be
      other risks for pre-eclampsia and intrauterine growth restriction, such as
      smoking and gestational diabetes.

PMID- 22395861
TI  - URG4 upregulation is associated with tumor growth and poor survival in epithelial
      ovarian cancer.
AB  - PURPOSE: Up-regulated gene 4 (URG4) has been demonstrated to be involved in
      progression of various human cancers. This study investigated the
      clinicopathological significance of URG4 in epithelial ovarian cancer (EOC).
      METHODS: Immunohistochemistry was applied to investigate the expression of URG4
      in ovarian tissues of 116 patients. The correlation of URG4 with proliferating
      cell nuclear antigen index (PCNA) was analyzed and the prognostic value of URG4
      in patients was also investigated. Pearson Chi-square test, Spearman correlation
      coefficient, univariate analysis, multivariate analysis, and Kaplan-Meier method
      were adopted. RESULTS: The positive rate of URG4 in EOC was higher than that in
      borderline and benign tumors (P = 0.001). URG4 was positively correlated with
      PCNA (r = 0.86, P = 0.006). In addition, univariate analysis showed URG4
      expression level, clinical stage, pathologic grade, lymphatic metastasis,
      chemotherapy, and ascites influenced survival time (all P < 0.05). In Cox
      multivariate analysis, all the aforementioned factors were found to be
      independent prognostic factors except pathologic grade and ascites (all P <
      0.05). CONCLUSIONS: Our results suggest for the first time that the URG4 might be
      involved in the progression of EOC. URG4 was a new target to assess the prognosis
      of EOC.

PMID- 22395862
TI  - Adenosine deaminase activity in patients with ovarian neoplasms.
AB  - PURPOSE: The aim of this study was to investigate the serum and peritoneal fluid
      adenosine deaminase (ADA) activity in patients with benign and malignant ovarian
      neoplasms. METHODS: This is a prospective cross-sectional study performed in
      Cukurova University, Department of Gynecologic Oncology. Eighty-four patients
      with ovarian mass were included in this study within 13 months. The levels of
      serum and peritoneal fluid ADA levels were measured and compared in patients with
      benign and malignant ovarian neoplasms and also low- and high-grade malignant
      tumors. RESULTS: Serum and peritoneal fluid ADA levels were found to be
      significantly higher in patients with ovarian cancers as compared with benign
      ovarian tumors (p = 0.001). Additionally, ADA levels were found to be
      significantly different according to the histopathological subtypes and grade of
      ovarian cancers. However, there was no significant difference for ADA levels
      between the benign and low-grade malignant tumors. There was an important
      correlation between the peritoneal fluid and serum ADA levels. CONCLUSIONS: Serum
      and peritoneal fluid ADA levels were found to be higher in malignant ovarian
      neoplasms. This finding may be useful to understand the biochemically
      characteristics of malignant ovarian tumors and ADA may be a useful biomarker in
      diagnosis and management of ovarian tumors.

PMID- 22395863
TI  - Detection and genotyping of cervical HPV with simultaneous cervical cytology in
      Turkish women: a hospital-based study.
AB  - PURPOSE: To investigate the prevalence of cervical human papilloma virus (HPV)
      with genotyping and simultaneous cervical cytology among Turkish women in a
      university hospital. A review of literature was done as well to summarize the
      results of similar Turkish studies based on hospital data. METHODS: Women who
      were subjected to cervical HPV-DNA testing with simultaneous cervical Pap test
      were included. Seeplex HPV 18-plex Genotyping Test was used for HPV detection and
      typing. Liquid-based cytology was used for Pap test and Bethesda system was used
      for results. RESULTS: Study group included 890 patients with a mean age of 39.5
      years. The prevalence of any HPV was 25.7% while high-risk HPV was positive in
      23.0%. There were no significant differences in HPV prevalence between younger
      and older women. Among HPV-positive women, 89.5% had at least one type of high
      risk HPV. Most common HPV was type 16 followed by type 31 and 51. Abnormal
      cervical cytology rate was 11.6%. Rate of HPV positivity was significantly higher
      in women with abnormal cervical cytology compared to women with normal cytology
      (54.4 vs. 22.0%). CONCLUSIONS: Cervical HPV infection is a serious and gradually
      growing problem for Turkish women according to hospital-based data. This may be
      associated with low age at marriage and more sensitive HPV detection methods.

PMID- 22395864
TI  - The sexual abuse of female children in Hungary: 20 years' experience.
AB  - INTRODUCTION: The purpose of this study is to describe the characteristics of
      female children who experience sexual abuse and explore common features that may
      assist in developing prevention strategies. MATERIALS AND METHODS: Between 1990
      and 2010, 266 girls under the age of 18 years, suspected of being sexually
      abused, visited the Department of Adolescent Gynecology. We retrospectively
      collected data illustrating the features of all cases. Seventy-eight percent of
      the victims were primary school students, and 45% of them were between 11 and 14
      years of age. RESULTS: The perpetrator knew the victim in 67% of the cases and
      was a stranger in 33%. Seventy-five (28%) perpetrators were members of the
      victims' families. In 14% of cases, the perpetrator was the victim's father and
      in 9% her stepfather. The abuse had occurred on multiple occasions in 29% of the
      cases. The occurrence rate of abuse was highest in the summer season (54%). As
      much as 63% of children experienced vaginal penetration, while 37% experienced a
      variety of sexual contact that did not involve penetration. Eighty-five victims
      were physically injured, and in 40 cases the presence of sperm was confirmed in
      vulvo-vaginal smears. A high proportion of female child sexual abuse takes place
      within the family and is revealed only after multiple episodes. The true
      prevalence of sexual abuse is being appreciated now that Hungarian law and
      society have recognized this societal problem. CONCLUSION: Prevention requires a
      systematic and lifelong approach to educating children about personal space and
      privacy and is the responsibility of parents and professionals.

PMID- 22395865
TI  - Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular
      cardiomyopathy 7 is caused by a DES mutation.
AB  - Using exome sequencing we searched for the genetic cause of autosomal dominant
      myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy (ARVC)
      in a Swedish family. A heterozygous C-to-T transition, c.1255C>T, p.Pro419Ser in
      the desmin gene on chromosome 2q35, was identified. Previous studies had
      demonstrated linkage to chromosome 10q22.3, but no causative mutation had been
      found in that region. Sanger sequencing of DNA from 17 family members confirmed
      the heterozygous c.1255C>T desmin mutation in seven out of ten family members
      that had been classified as affected in the previous study. Our new results
      demonstrate the usefulness of next-generation sequencing, and the diagnostic
      difficulties with some forms of dominantly inherited muscle diseases as they can
      display a wide clinical and morphological variability even within a given family.

PMID- 22395866
TI  - Male and female differential reproductive rate could explain parental
      transmission asymmetry of mutation origin in Hirschsprung disease.
AB  - Hirschsprung disease (HSCR, aganglionic megacolon) is a complex and heterogeneous
      disease with an incidence of 1 in 5000 live births. Despite the multifactorial
      determination of HSCR in the vast majority of cases, there is a monogenic
      subgroup for which private rare RET coding sequence mutations with high
      penetrance are found (45% of HSCR familial cases). An asymmetrical parental
      origin is observed for RET coding sequence mutations with a higher maternal
      inheritance. A parent-of-origin effect is usually assumed. Here we show that a
      differential reproductive rate for males and females also leads to an
      asymmetrical parental origin, which was never considered as a possible
      explanation till now. In the case of HSCR, we show a positive association between
      penetrance of the mutation and parental transmission asymmetry: no parental
      transmission asymmetry is observed in sporadic RET CDS mutation carrier cases for
      which penetrance of the mutation is low, whereas a parental transmission
      asymmetry is observed in affected sib-pairs for which penetrance of the mutation
      is higher. This allows us to conclude that the explanation for this parental
      asymmetry is that more severe mutations have resulted in a differential
      reproductive rate between male and female carriers.

PMID- 22395867
TI  - A 600 kb triplication in the cat eye syndrome critical region causes anorectal,
      renal and preauricular anomalies in a three-generation family.
AB  - Cat eye syndrome (CES) is caused by a gain of the proximal part of chromosome 22.
      Usually, a supernumerary marker chromosome is present, containing two extra
      copies of the chromosome 22q11.1q11.21 region. More sporadically, the gain is
      present intrachromosomally. The critical region for CES is currently estimated to
      be about 2.1 Mb and to contain at least 14 RefSeq genes. Gain of this region may
      cause ocular coloboma, preauricular, anorectal, urogenital and congenital heart
      malformations. We describe a family in which a 600 kb intrachromosomal
      triplication is present in at least three generations. The copy number alteration
      was detected using MLPA and further characterized with interphase and metaphase
      FISH and SNP-array. The amplified fragment is located in the distal part of the
      CES region. The family members show anal atresia and preauricular tags or pits,
      matching part of the phenotype of this syndrome. This finding suggests that
      amplification of the genes CECR2, SLC25A18 and ATP6V1E1, mapping within the
      critical region for CES, may be responsible for anorectal, renal and preauricular
      anomalies in patients with CES.

PMID- 22395868
TI  - Surface damage versus tibial polyethylene insert conformity: a retrieval study.
AB  - BACKGROUND: Surface damage of the tibial polyethylene insert in TKA is thought to
      diminish with increasing conformity, based on computed lower contact stresses.
      Added constraint from higher conformity may, however, result in greater forces in
      vivo. QUESTIONS/PURPOSES: We therefore determined whether increased conformity
      was associated with increased surface pitting, delamination, creep, and polishing
      in a group of retrieved tibial inserts. METHODS: We compared 38 inserts with a
      dished articular surface (conforming group) with 31 inserts that were
      unconstrained and nonconforming in the sagittal plane (less conforming group).
      The two groups had identical polyethylene composition and processing history. The
      articulating surfaces were scored for pitting, delamination, deformation/creep,
      and polishing. Evidence of edge loading and the presence of embedded bone cement
      were also recorded. RESULTS: The conforming inserts were associated with higher
      delamination and pitting scores but lower polishing scores, even after adjusting
      for the effects of sex, age, insert thickness, and implantation duration. Long
      implantation duration and male sex were also associated with increased
      delamination, pitting, and polishing, whereas long shelf life was associated only
      with increased delamination. The conforming group also had approximately a
      fourfold greater prevalence of edge loading and approximately a threefold greater
      prevalence of embedded bone cement. The latter was associated with higher scores
      and proportions of delamination and pitting. CONCLUSIONS: These findings suggest
      more conformity may increase surface fatigue damage in TKA. Higher constraint
      induced stresses during secondary motions and more possibility for edge loading
      and bone cement capture on a dished surface may account for these results.
      CLINICAL RELEVANCE: The selection of materials with high fatigue resistance may
      be particularly important for high-conformity/constraint tibial inserts. In
      addition, awareness of the benefits and trade-offs with conformity may allow
      better matching of TKA design to patient.

PMID- 22395869
TI  - Beyond the standard of care: a new model to judge medical negligence.
AB  - BACKGROUND: The term "standard of care" has been used in law and medicine to
      determine whether medical care is negligent. However, the precise meaning of this
      concept is often unclear for both medical and legal professionals.
      QUESTIONS/PURPOSES: Our purposes are to (1) examine the limitations of using
      standard of care as a measure of negligence, (2) propose the use of the legal
      concepts of justification and excuse in developing a new model of examining
      medical conduct, and (3) outline the framework of this model. METHODS: We applied
      the principles of tort liability set forth in the clinical and legal literature
      to describe the difficulty in applying standard of care in medical negligence
      cases. Using the concepts of justification and excuse, we propose a judicial
      model that may promote fair and just jury verdicts in medical negligence cases.
      RESULTS: Contrary to conventional understanding, medical negligence is not simply
      nonconformity to norms. Two additional concepts of legal liability, ie,
      justification and excuse, must also be considered to properly judge medical
      conduct. Medical conduct is justified when the benefits outweigh the risks; the
      law sanctions the conduct and encourages future conduct under similar
      circumstances. Excuse, on the other hand, relieves a doctor of legal liability
      under specific circumstances even though his/her conduct was not justified.
      CONCLUSIONS: Standard of care is an inaccurate measure of medical negligence
      because it is premised on the faulty notion of conformity to norms. An
      alternative judicial model to determine medical negligence would (1) eliminate
      standard of care in medical malpractice law, (2) reframe the court instruction to
      jurors, and (3) establish an ongoing consensus committee on orthopaedic
      principles of negligence.

PMID- 22395870
TI  - Spinal cord injury resulting from injury missed on CT scan: the danger of relying
      on CT alone for collar removal.
AB  - BACKGROUND: Strict criteria have been used before removing cervical collars in
      patients with injuries who have midline pain or are unable to be reliably
      examined. This sometimes leads to prolonged immobilization in cervical collars or
      use of MRI to rule out injury. Several studies suggest a collar may be removed in
      the absence of fractures, dislocation, or pathologic subluxation on a cervical CT
      scan. This may avoid the morbidity of prolonged cervical immobilization or cost
      of advanced imaging study but risks devastating consequences from missing
      injuries. CASE DESCRIPTION: We report a patient with a cervical spinal cord
      injury after removal of a collar after a CT scan was misinterpreted as normal.
      Retrospective review of the CT showed subtle signs of widening between the
      spinous processes of the injured level, a finding easily missed without the use
      of further imaging studies. LITERATURE REVIEW: Several articles suggest cervical
      collars may be safely removed from awake and alert patients and in patients who
      cannot be reliably examined after a negative CT scan without the need for further
      imaging. PURPOSES AND CLINICAL RELEVANCE: CT scans are excellent at detecting
      bony injuries but not ligamentous injuries. Removing cervical collars based on CT
      scans alone may be expeditious, but some injuries may be missed without further
      imaging. Our case demonstrates the catastrophic consequences of missing a
      cervical spine injury and emphasizes the need for maintaining the cervical collar
      in high-risk patients until proper imaging can be obtained.

PMID- 22395871
TI  - Measuring acetabular component version after THA: CT or plain radiograph?
AB  - BACKGROUND: Although cross-table lateral radiographs are commonly used to measure
      acetabular component version after THA, recent studies suggest that CT-based
      measurement is more accurate. This has been attributed to variations in pelvic
      tilt, pelvic rotation, and component inclination. Furthermore, it has been
      suggested, based on limited data, that even with ideal positioning of the cross
      table lateral radiograph, CT remains the more accurate modality.
      QUESTIONS/PURPOSES: We determined whether appropriately positioned cross-table
      lateral radiographs could provide accurate measurements of acetabular component
      version, and compared accuracy and reliability of measurements from modified
      cross-table lateral radiographs with those from standard cross-table lateral
      radiographs and CT. METHODS: We implanted 27 Sawbones pelves with an acetabular
      cup using computer navigation. CT, an AP view of the pelvis, and cross-table
      lateral and modified cross-table lateral radiographs were performed for each
      specimen. For the modified cross-table lateral radiograph, the beam angle varied
      based on the cup inclination as measured on an AP view of the pelvis. Two
      independent observers measured acetabular component version and inclination. We
      calculated intraobserver and interobserver reliabilities for each method and
      compared these with values obtained from navigation presuming that to be the
      standard for judging accuracy. RESULTS: Interobserver and intraobserver
      reliabilities were greater than 0.95 (95% CI, 0.904-0.999) for all measurements.
      Correlation with navigated values was 0.96 or greater (95% CI, 0.925-0.998) for
      all methods. Although CT had the highest correlation with navigated values, the
      correlations for the modified cross-table lateral and cross-table lateral
      radiographs were similar. CONCLUSION: CT allows for accurate measurement of
      acetabular component version; however, when properly positioned, cross-table
      lateral radiograph-derived measurements are similarly accurate. CLINICAL
      RELEVANCE: Our results support the use of plain radiographs to obtain important
      measurements after THA.

PMID- 22395872
TI  - Total hip arthroplasty versus hemiarthroplasty for displaced femoral neck
      fractures: meta-analysis of randomized trials.
AB  - BACKGROUND: Most patients with displaced femoral neck fractures are treated by
      THA and hemiarthroplasty, but it remains uncertain which if either is associated
      with better function and lower risks of complications. QUESTIONS/PURPOSES: We
      performed a meta-analysis of randomized controlled trials (RCTs) to determine
      whether THA was associated with lower rates of reoperations, mortality,
      complications, and better function compared with hemiarthroplasty. METHODS: We
      searched the PubMed, Embase, Chinese Biomedicine Literature, and Cochrane
      Register of Controlled Trials databases and identified 12 RCTs (including a total
      of 1320 patients) for meta-analysis. Risk ratios (RRs) and weighted mean
      differences (WMDs) from each trial were pooled using random-effects or fixed
      effects models depending on the heterogeneity of the included studies. RESULTS:
      THA was associated with a lower risk of subsequent reoperations compared with
      hemiarthroplasty (RR = 0.53; 95% CI, 0.34-0.84). There was no difference in
      mortality between patients undergoing THA and hemiarthroplasty (RR = 0.81; 95%
      CI, 0.60-1.09). For complications, there was a higher risk of dislocation in
      patients undergoing THA (RR = 1.99; 95% CI, 1.26-3.15), but there were no
      differences in local infections (RR = 1.60; 95% CI, 0.74-3.46) and general
      complications (RR = 1.15; 95% CI, 0.91-1.45). Patients with THA had higher Harris
      hip scores at 1 year (WMD = 3.81; 95% CI, 0.87-6.74) and at 3 or 4 years (WMD =
      10.07; 95% CI, 6.92-13.21). CONCLUSIONS: Despite more dislocations, THA can
      benefit patients with displaced femoral neck fractures with a lower reoperation
      rate and higher functional scores.

PMID- 22395873
TI  - Return to play after Type II superior labral anterior-posterior lesion repairs in
      athletes: a systematic review.
AB  - BACKGROUND: Superior labral anterior-posterior (SLAP) lesions are a common cause
      of pain and disability in athletes. Individual studies have suggested low patient
      satisfaction with SLAP repairs in throwing athletes in particular and it is
      unclear how frequently athletes return to their previous level of competetion.
      QUESTIONS/PURPOSES: We systematically reviewed the literature to determine (1)
      patient satisfaction and (2) return to play at previous level of competition
      among throwing athletes compared to all athletes who underwent repair of Type II
      SLAP tears using various types of fixation. METHODS: We searched databases for
      English-language articles in peer-reviewed journals from 1950 to 2010 reporting
      Type II SLAP repairs with 2-year followup for our systematic review. A total of
      506 patients with Type II SLAP tears were reviewed from 14 studies; of these, 327
      had SLAP lesions repaired by anchor, 169 by tacks, and 10 by staples. Of the 506
      patients, 198 were overhead athletes with a pooled subset of 81 identified
      baseball players. RESULTS: For the entire patient population, 83% had "good-to
      excellent" patient satisfaction and 73% returned to their previous level of play
      whereas only 63% of overhead athletes returned to their previous level of play.
      Anchor repair in overhead athletes resulted in a higher percentage of "good-to
      excellent" patient satisfaction (88% versus 74%) and a slightly higher return to
      play rate (63% versus 57%) compared with tack repair. CONCLUSIONS: Repair of Type
      II SLAP tears leads to a return to previous level of play in most patients.
      Overhead athletes appear to have a lower rate of return to level of previous of
      play. Anchor fixation appears to be the most favorable fixation in both
      subjective scores and return to previous level of play.

PMID- 22395874
TI  - Neer modification of open Bankart procedure: what are the rates of recurrent
      instability, functional outcome, and arthritis?
AB  - BACKGROUND: Neer modified the Bankart procedure by combining a superoinferior
      capsular shift with the labral reattachment. The theoretical advantages of the
      modification were that such a procedure would restore the patient's anatomy and
      also treat the repeated capsular stretching encountered in anteroinferior
      instability without limiting external rotation and, thereby reducing the risk of
      arthritis. QUESTIONS/PURPOSES: We therefore determined: (1) the rate of recurrent
      instability after this modification, (2) patient function, and (3) the incidence
      and stage of glenohumeral osteoarthritis at greater than 2 years followup in
      patients with traumatic anteroinferior instability. METHODS: We retrospectively
      reviewed all 64 patients (average age, 27 years) who had the modified Bankart
      procedure for recurrent dislocations (n = 39) or subluxation (n = 25) from 1991
      to 1997. The labrum was reattached with suture anchors and a superoinferior
      capsular shift was added. We determined the rate of recurrent instability, Rowe
      and Walch-Duplay scores and shoulder ROM, and the presence of glenohumeral
      osteoarthritis (modified Samilson and Prieto classification). The minimum
      followup was 24 months (median, 40 months; range, 24-120 months). RESULTS:
      Recurrent instability occurred in seven of the 64 patients (11%) at an average of
      25 months postoperatively (range, 7 days to 6 years); in six patients the
      recurrence was associated with trauma; five of the six patients underwent
      reoperation with a Latarjet procedure. Eight additional patients (13%) presented
      with persistent shoulder apprehension or discomfort. The average Rowe score was
      83% (range, 20-100%) and average Walch-Duplay score 83% (range, 15-100%).
      However, only 36 of 64 (56%) patients could return to the same sport at the same
      level. The loss of external rotation was 13 degrees  compared with the
      contralateral side. Glenohumeral osteoarthritis incidence increased from 4%
      preoperatively to 17% postoperatively. CONCLUSIONS: The open Bankart procedure
      modified by Neer provided high function scores but a relatively low rate of
      return to sport and high rate of recurrent instability. Our rate of recurrent
      instability, similar to that obtained with arthroscopic Bankart procedures, has
      prompted us to abandon the open procedure.

PMID- 22395875
TI  - Is drusen area really so important? An assessment of risk of conversion to
      neovascular AMD based on computerized measurements of drusen.
AB  - PURPOSE: To assess the relative risk of an eye's conversion to wet age-related
      macular degeneration (AMD) based primarily on drusen measurements obtained from
      analysis of digitized images. METHODS: Four hundred forty-four subjects (820
      eyes) enrolled in the Age-Related Eye Disease Study (AREDS I) and 78 subjects
      (129 eyes) from the Prophylactic Treatment of AMD trial (PTAMD) were studied
      retrospectively. Drusen size, distribution, drusen area, and hyperpigmentation in
      two central macular regions on baseline fundus images were determined using an
      image analysis algorithm. The relative risk for choroidal neovascularization
      (CNV) based on drusen area, presence of one or five large drusen,
      hyperpigmentation, and fellow eye status was calculated. RESULTS: Odds ratios
      (ORs) for measured drusen area within the 1000- and 3000-MUm regions were 1.644*
      (1.251-2.162) and 1.278 (0.927-1.762) for AREDS eyes and 0.832 (0.345-2.005) and
      1.094 (0.524-2.283) for PTAMD eyes (*P < 0.05). In the 1000-MUm region,
      respective ORs for the presence of a large druse, hyperpigmentation, and fellow
      eye affected were 2.60, 1.71, and 6.44* for AREDS eyes and 8.24, 1.37, and 17.56*
      for PTAMD eyes; for the 3000-MUm region, ORs were 3.45*, 3.40*, and 4.59* for
      AREDS and nonsignificant, 6.58, and 11.62* for PTAMD eyes, respectively.
      CONCLUSIONS: Total drusen area, presence of large drusen, and the presence of
      hyperpigmentation were not consistent risk factors for an eye's development of
      CNV. Risk depended on study cohort as well as location. Having an affected fellow
      eye was the strongest and most consistent risk factor across all models. A larger
      drusen area does not necessarily increase an eye's risk of conversion to CNV.

PMID- 22395876
TI  - Autoantibodies contribute to the immunopathogenesis of experimental dry eye
      disease.
AB  - PURPOSE: The purpose of this study was to determine if autoantibodies play a role
      in the immunopathogenesis of experimental dry eye disease. METHODS: Dry eye was
      induced by exposing female C57BL/6 wild-type mice or hen egg lysozyme B-cell
      receptor transgenic mice to desiccating stress (subcutaneous scopolamine [0.5
      mg/0.2 mL] 3 times a day, humidity < 40%, and sustained airflow) for 3 weeks,
      allowing sufficient time for a humoral immune response. Serum or purified IgG
      isolated from dry-eye mice or untreated controls was passively transferred to
      nude recipient mice, which were evaluated for ocular surface inflammation 3 days
      after transfer. To determine if complement activation contributed to serum
      induced dry eye disease, cobra venom factor was used to deplete complement
      activity. RESULTS: Autoantibodies against kallikrein 13 were identified in serum
      from dry-eye mice, but were undetectable in untreated controls. Autoantibody
      containing serum or purified IgG from dry-eye mice was sufficient to mediate
      complement-dependent ocular surface inflammation. Serum or purified IgG caused
      marked inflammatory burden and tissue damage within the ocular surface tissues,
      including elevated Gr1+ neutrophil infiltration and proinflammatory
      cytokines/chemokines associated with goblet cell loss. Moreover, complement C3b
      deposition was found within the ocular surface tissues of mice receiving dry-eye
      serum, but not in recipients of control serum. Functionally, complement depletion
      attenuated the ability to transfer dry-eye-specific serum or IgG-mediated
      disease. CONCLUSIONS: These data demonstrate for the first time a complement
      dependent pathogenic role of dry-eye-specific autoantibodies, and suggest
      autoantibody deposition within the ocular surface tissues contributes to the
      predominantly T-cell-mediated immunopathogenesis of dry eye disease.

PMID- 22395877
TI  - Retinal oximetry images must be standardized: a methodological analysis.
AB  - PURPOSE: Retinal vessel oximetry is a new technology and needs detailed
      methodological scrutiny. We determine (1) the repeatability of retinal vessel
      oxygen saturation measurements, (2) whether measured saturation is different
      between retinal quadrants, and (3) whether the angle of gaze changes measurements
      of the same vessels. METHODS: Fundus oximetry images were obtained from 26
      healthy individuals, 18 to 30 years old, using the Oxymap retinal oximeter.
      Oxygen saturation in the same vessel segments was compared between two similar
      images of each individual to determine repeatability. Vessel oxygen saturation
      was also compared between different quadrants of the retina in the same oximetry
      image. Finally, oxygen saturation measurements were made on the same vessel
      segments at different angles of gaze. RESULTS: Mean and standard deviation of
      saturation measurements was 93.1% +/- 2.3% in arterioles and 64.9% +/- 3.3% in
      venules. Standard deviation of repeated saturation measurements on the same
      vessel segment was 1.0% in arterioles and 1.4% in venules. Significant
      differences were seen between retinal quadrants. When angle of gaze was altered,
      measured saturation was lower in the same vessels when they were located in the
      inferior portion compared with other parts of the image (-1.3% +/- 1.7%, P =
      0.0004 in arterioles and -1.9 +/- 2.4%, P = 0.0007 in venules). CONCLUSIONS:
      Retinal vessel oxygen saturation measurements are repeatable with a small
      standard deviation. When oximetry results are compared between time points or
      eyes, the imaging must be standardized and similar parts of the images analyzed.

PMID- 22395878
TI  - Contribution of genetic and environmental effects on lens thickness: the
      Guangzhou Twin Eye study.
AB  - PURPOSE: This study investigated the heritability of lens thickness (LT) and
      relative lens thickness (LT/axial length, rLT) measured by Lenstar among Chinese
      children and adolescents in the Guangzhou Twin Eye study. METHODS: Twins aged 8
      to 22 years were enrolled from the Guangzhou Twin Registry. A series of LT and
      axial length (AL) measurements using the Lenstar were taken for each twin.
      Zygosity was confirmed by genotyping in all same-sex twin pairs. Heritability was
      assessed by structural variance component genetic modeling, after adjustment for
      age and sex with the Mx program. RESULTS: Seven hundred sixty-eight twin pairs
      (482 monozygotic [MZ] and 286 dizygotic [DZ] twins) were available for data
      analysis. The mean (standard deviation) LT and rLT were 3.45 (0.18) mm and 0.142
      (0.01), respectively. The intraclass correlation coefficients (ICCs) for LT were
      0.90 for the MZ and 0.39 for the DZ twins; and those for rLT were 0.90 for the MZ
      and 0.40 for the DZ twins, respectively. The best-fitting model yielded 89.5%
      (95% CI: 87.8%-91.0%) of additive genetic effects and 10.5% (95% CI: 9.0%-12.2%)
      of unique environmental effects for LT, and 89.3% (95% CI: 89.2%-89.3%) of
      additive genetic effects and 10.7% (95% CI: 10.7%-11.4%) of unique environmental
      effects for rLT. CONCLUSIONS: This study confirms that the LT in young healthy
      subjects may be mainly affected by additive genetic factors. High heritability
      remains even when the data are corrected for the influence of AL with the use of
      rLT.

PMID- 22395879
TI  - Preferred retinal locus--hand coordination in a maze-tracing task.
AB  - PURPOSE: Fine manual tasks require coordination of vision, eye movements, and
      motor control. Macular scotomas from age-related macular degeneration (AMD) may
      adversely affect this coordination. The purpose of this research was to find
      whether the preferred retina locus for fixation (fPRL) also guided the hand in
      performing fine manual tasks and how the fingers, fPRL, and scotomas interacted
      in task performance. METHODS: Subjects with bilateral macular scotomas from AMD
      and normally sighted controls traced an irregular "maze" line pattern with the
      index finger while viewing their hand and the maze in a scanning laser
      ophthalmoscope (SLO). Video images from the SLO showing the fingers and maze on
      the retina during the task were analyzed to produce retinal maps showing the
      scotoma and bivariate ellipses of fPRL and fingertip retinal positions. RESULTS:
      Fingertip retinal ellipses surrounded and were approximately centered on the fPRL
      ellipses. Fingertip retinal bivariate area was positively correlated with fPRL
      bivariate area and the percent time the fPRL was on the maze was correlated with
      visual acuity. Maze-tracing accuracy was positively correlated with saccade rate
      for scotoma subjects. CONCLUSIONS: Concentric overlap of fPRL and fingertip
      retinal ellipses indicates that it is the fPRL that guides the hand in the maze
      tracing visuomotor task, just as the fovea guides the fingertip for visually
      normal subjects. It is likely that factors other than fPRL and scotoma
      characteristics contribute to poorer maze-tracing performance by scotoma subjects
      in comparison with controls.

PMID- 22395880
TI  - The clinical differentiation of bacterial and fungal keratitis: a photographic
      survey.
AB  - PURPOSE: The purpose of this study was to determine whether clinical signs of
      infectious keratitis can be used to identify the causative organism. METHODS:
      Eighty photographs of eyes with culture-proven bacterial keratitis or smear
      proven fungal keratitis were randomly selected from 2 clinical trials. Fifteen
      cornea specialists from the F. I. Proctor Foundation and the Aravind Eye Care
      System assessed the photographs for prespecified clinical signs of keratitis, and
      they identified the most likely causative organism. RESULTS: Clinicians were able
      to correctly distinguish bacterial from fungal etiology 66% of the time (P <
      0.001). The Gram stain, genus, and species were accurately predicted 46%, 25%,
      and 10% of the time, respectively. The presence of an irregular/feathery border
      was associated with fungal keratitis, whereas a wreath infiltrate or an
      epithelial plaque was associated with bacterial keratitis. CONCLUSIONS: Cornea
      specialists correctly differentiated bacterial from fungal keratitis more often
      than chance, but in fewer than 70% of cases. More specific categorization led to
      less successful clinical distinction. Although certain clinical signs of
      infectious keratitis may be associated with a bacterial or fungal etiology, this
      study highlights the importance of obtaining appropriate microbiological testing
      during the initial clinical encounter.

PMID- 22395881
TI  - Precision of high definition spectral-domain optical coherence tomography for
      measuring central corneal thickness.
AB  - PURPOSE: This study was intended to assess the reliability of central corneal
      thickness (CCT) measurements using Cirrus high-definition optical coherence
      tomography (HD-OCT) in healthy subjects and its accuracy compared with ultrasonic
      pachymetry. METHODS: Seventy-seven consecutive subjects were recruited for
      evaluating repeatability, and agreement between two examiners. To analyze
      repeatability, one examiner measured 77 eyes four times in succession. To study
      agreement between two observers, a second independently trained examiner obtained
      another CCT measurement. We also measured eyes in a subgroup of 20 patients using
      standard ultrasonic pachymetry. Within-subject standard deviation (S(w)),
      coefficient of variation (CV), limits of agreement (LoA), and intraclass
      correlation coefficient (ICC) data were obtained. RESULTS: For repeatability, the
      S(w) and precision (1.96 * S(w)) were 4.86 and 9.52 MUm, respectively.
      Intraobserver CV was 0.89% and the ICC was 0.98 (95% confidence interval [CI],
      0.97-0.99). For agreement between two examiners, the S(w) and precision were 7.58
      and 14.85 MUm, respectively; the CV was 1.40%. The mean difference between
      observers was -0.13 MUm (95% CI, -1.85 to 1.58; P = 0.87). The width of the LoA
      was 29.64 MUm. Median difference between Cirrus HD-OCT and ultrasound CCT
      measurements was -4.5 MUm (interquartile range, -7.0-0.0; P = 0.04). CONCLUSIONS:
      Cirrus HD-OCT provides repeatable CCT measurements, good agreement between two
      independently trained examiners, and its systematic bias compared to ultrasonic
      pachymetry is clinically negligible. Therefore, research laboratories and eye
      clinics using Cirrus HD-OCT as a diagnostic imaging method, can also benefit from
      a reliable noncontact pachymeter when counseling patients with glaucoma and those
      undergoing corneal and refractive surgeries.

PMID- 22395882
TI  - Imaging of the iridocorneal angle with the RTVue spectral domain optical
      coherence tomography.
AB  - PURPOSE: To determine the ability of the RTVue spectral domain optical coherence
      tomography (SDOCT) to image the anterior chamber angle (ACA). METHODS:
      Consecutive subjects, recruited from glaucoma clinics, prospectively underwent
      ophthalmic evaluation including gonioscopy by an ophthalmologist and anterior
      chamber imaging with SDOCT, adapted with a corneal lens adapter (cornea anterior
      module-low magnification [CAM-L]) and anterior segment OCT (ASOCT), both
      performed by a technician. Two different ophthalmologists, masked to gonioscopy
      findings, assessed visualization of the scleral spur (SS), Schwalbe's line (SL),
      and trabecular meshwork (TM) by the two modalities. The ability to detect a
      closed angle was compared with gonioscopy. RESULTS: The average age (SD) of the
      81 subjects enrolled was 64.1 (11.4) years; the majority were Chinese (91.4%) and
      female (61.7%). SDOCT images revealed the SS in 26.9% (56/324) of quadrants and
      the SL in 44.1% (143/324) of quadrants; in ASOCT images, the SS could be
      visualized in 69.1% (224/324) of quadrants (P < 0.0001), but the SL was
      undetectable. The TM was detected equally well (17.3%, P < 0.92) using either
      device. The angle status was gradable in only 41.7% images with SDOCT, compared
      with 71.3% of ASOCT images (P < 0.0001). ACA was classified as closed in 19.3% of
      quadrants (26/135) with SDOCT images and in 44.2% (102/231) with ASOCT images
      compared with 37.7% (122/324) on gonioscopy. When analyzing the horizontal
      quadrants only, both modalities agreed well with gonioscopy, 0.75 and 0.74,
      respectively (AC1 statistics). CONCLUSIONS: The RTVue SDOCT allowed visualization
      of SL, TM, and SS. However, these landmarks were not detected in a large
      percentage of images.

PMID- 22395884
TI  - Mapping the corneal sub-basal nerve plexus in orthokeratology lens wear using in
      vivo laser scanning confocal microscopy.
AB  - PURPOSE: This study was designed to map the sub-basal nerve plexus (SBNP) in the
      cornea of orthokeratology (OK) lens wearers. METHODS: Laser scanning confocal
      microscopy (LSCM) was performed in vivo on three subjects: a non-lens wearer and
      two OK lens wearers. Scans were performed on the right eye while the left eye
      fixated a moving target. A total of 575, 430, and 676 contiguous images of the
      SBNP were taken from the non-lens wearing and the OK lens wearing subjects,
      respectively, and used to construct maps of the central to mid-peripheral SBNP.
      RESULTS: In the non-lens wearing eye, nerves radiated towards a whorl-like
      complex centered nasally and inferiorly in an overall pattern consistent with
      previously reported studies. In the OK lens wearing eyes, this whorl pattern was
      absent, replaced by a tortuous network of nerve fibers centrally, and thicker
      curvilinear fibers mid-peripherally, particularly in the nasal, inferior, and
      temporal regions. CONCLUSIONS: This study maps the corneal SBNP in OK lens
      wearers and provides compelling evidence that OK lens wear alters the normal SBNP
      distribution observed in healthy, non-lens wearing eyes.

PMID- 22395883
TI  - Biomechanics of the human posterior sclera: age- and glaucoma-related changes
      measured using inflation testing.
AB  - PURPOSE: The objective of this study was to measure the biomechanical response of
      the human posterior sclera in vitro and to estimate the effects of age and
      glaucoma. METHODS: Scleral specimens from 22 donors with no history of glaucoma
      and 11 donors with a history of glaucoma were excised 3 mm posterior to the
      equator and affixed to an inflation chamber. Optic nerve cross-sections were
      graded to determine the presence of axon loss. The time-dependent inflation
      response was measured in a series of pressure-controlled load-unload tests to 30
      mm Hg and creep tests to 15 and 30 mm Hg. Circumferential and meridional strains
      were computed from the digital image correlation displacements, and midposterior
      stresses were determined from pressure and deformed geometry. RESULTS: Among
      normal specimens, older age was predictive of a stiffer response and a thinner
      sclera. In the age group 75 to 93, diagnosed glaucoma eyes with axon damage were
      thicker than normal eyes. Both damaged and undamaged glaucoma eyes had a
      different strain response in the peripapillary sclera characterized by a stiffer
      meridional response. Undamaged glaucoma eyes had slower circumferential creep
      rates in the peripapillary sclera than normal eyes. Glaucoma eyes were not
      different from normal eyes in stresses and strains in the midposterior sclera.
      CONCLUSIONS: The observed differences in the biomechanical response of normal and
      glaucoma sclera may represent baseline properties that contribute to axon damage,
      or may be characteristics that result from glaucomatous disease.

PMID- 22395885
TI  - Elevation of serum asymmetrical and symmetrical dimethylarginine in patients with
      advanced glaucoma.
AB  - PURPOSE: Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA)
      are the dimethylated isomeric derivatives of the amino acid L-arginine. ADMA is
      an endogenous inhibitor of nitric oxide synthase (NOS), while SDMA is a
      competitive inhibitor of cellular uptake of L-arginine, the substrate for NOS. As
      such, these metabolites are associated with endothelial dysfunction. As the
      nitric oxide pathway and endothelial dysfunction have been implicated in
      glaucoma, the aim of this study was to investigate serum ADMA, SDMA, and L
      arginine levels in individuals with advanced glaucoma compared with normal
      controls. In addition, we have investigated genetic variation in the DDAH1 and
      DDAH2 genes, encoding the enzymes responsible for degradation of ADMA, for
      association with ADMA level in glaucoma patients and controls. METHODS: Two
      hundred eleven patients with advanced glaucoma and 295 normal controls were
      recruited. Liquid chromatography-tandem mass spectrometry was used to measure the
      serum ADMA, SDMA, and L-arginine levels of participants. Single nucleotide
      polymorphisms in the DDAH1 and DDAH2 genes reportedly associated with ADMA level
      were genotyped in all individuals. RESULTS: A significant increase in both serum
      ADMA and SDMA concentration was detected in advanced glaucoma cases compared with
      controls (P <= 0.0001). No significant change was detected in serum L-arginine
      concentration. No association of polymorphisms in DDAH1 and DDAH2 with either
      ADMA level or glaucoma was detected. CONCLUSIONS: The serum levels of two
      dimethylarginines, ADMA and SDMA, are associated with advanced glaucoma. These
      data further implicate the nitric-oxide pathway in glaucoma pathogenesis.

PMID- 22395886
TI  - Retinal intrinsic optical signals in a cat model of primary congenital glaucoma.
AB  - PURPOSE: To examine the impact of reduced inner retinal function and breed on
      intrinsic optical signals in cats. METHODS: Retinal intrinsic optical signals
      were recorded from anesthetized cats with a modified fundus camera. Near infrared
      light (NIR, 700-900 nm) was used to illuminate the retina while a charge-coupled
      device (CCD) camera captured the NIR reflectance of the retina. Visible stimuli
      (540 nm) evoked patterned changes in NIR retinal reflectance. NIR intrinsic
      signals were compared across three subject groups: two Siamese cats with primary
      congenital glaucoma (PCG), a control Siamese cat without glaucoma, and a control
      group of seven normally pigmented cats. Intraocular pressure (IOP), pattern
      electroretinogram, and optical coherence tomography measurements were evaluated
      to confirm the inner retinal deficit in PCG cats. RESULTS: Stimulus-evoked, NIR
      retinal reflectance signals were observed in PCG cats despite severe degeneration
      of the nerve fiber layer and inner retinal function. The time course, spectral
      dependence, and spatial profile of signals imaged in PCG cats were similar to
      signals measured from normal and Siamese control cats. CONCLUSIONS: Despite
      increased IOP, reduced nerve fiber layer thickness and ganglion cell function,
      intrinsic optical signals persist in cats affected with PCG. The mechanisms
      giving rise to intrinsic signals remain despite inner retinal damage. Signal
      strength was reduced in all Siamese cats compared to controls, suggesting that
      reduced intrinsic signals in PCG cats represent a difference between breeds
      rather than loss of ganglion cells. These results corroborated previous findings
      that retinal ganglion cells are not the dominant source of intrinsic optical
      signals of the retina.

PMID- 22395887
TI  - Mass spectrometric identification of phospholipids in human tears and tear
      lipocalin.
AB  - PURPOSE: The purpose of this article was to identify by mass spectrometry
      phosphocholine lipids in stimulated human tears and determine the molecules bound
      to tear lipocalin or other proteins. METHODS: Tear proteins were separated
      isocratically from pooled stimulated human tears by gel filtration fast
      performance liquid chromatography. Separation of tear lipocalin was confirmed by
      SDS tricine gradient PAGE. Protein fractions were extracted with
      chloroform/methanol and analyzed with electrospray ionization MS/MS triple
      quadrupole mass spectrometry in precursor ion scan mode for select leaving
      groups. For quantification, integrated ion counts were derived from standard
      curves of authentic compounds of phosphatidylcholine (PC) and phosphatidylserine.
      RESULTS: Linear approximation was possible from integration of the mass
      spectrometrically obtained ion peaks at 760 Da for the PC standard. Tears
      contained 194 ng/mL of the major intact PC (34:2), m/z 758.6. Ten other
      monoisotopic phosphocholines were found in tears. A peak at 703.3 Da was assigned
      as a sphingomyelin. Four lysophosphatidylcholines (m/z 490-540) accounted for
      about 80% of the total integrated ion count. The [M+H](+) compound, m/z 496.3,
      accounted for 60% of the signal intensity. Only the tear lipocalin-bearing
      fractions showed phosphocholines (104 ng/mL). Although the intact phospholipids
      bound to tear lipocalin corresponded precisely in mass and relative signal
      intensity to that found in tears, we did not identify phosphocholines between m/z
      490 and 540 in any of the gel-filtration fractions. CONCLUSIONS: Phospholipids,
      predominantly lysophospholipids, are present in tears. The higher mass intact PCs
      in tears are native ligands of tear lipocalin.

PMID- 22395890
TI  - Anti-retinal antibodies in serum of laser-treated rabbits.
AB  - PURPOSE: Retinal injuries that affect the photoreceptors and/or the retinal
      pigment epithelium (RPE) may result in the leakage of retinal proteins into the
      systemic circulation. This study was designed to determine whether an immune
      response is elicited after an acute retinal injury resulting in circulating anti
      retinal antibodies in the serum. METHODS: Fifty laser burns of different grades
      (minimally visible lesion [MVL], grade II [GII], or grade III [GIII] lesions)
      were created in the retinas of Dutch Belted rabbits. The degree of laser burns
      was confirmed by fundus imaging and histology. Serum samples were collected from
      the animals 3 months after the retinal injury. Candidate autoantigens were
      identified by two-dimensional (2-D) Western blots of rabbit retinal lysate probed
      with sera from either control or laser-treated animals. Candidate autoantigens
      were further characterized by immunostaining to confirm their retinal
      localization. RESULTS: Seven and 11 protein spots were selected from the MVL and
      GII laser-treated samples, respectively, for autoantigen identification. No
      protein spots were detected in the GIII laser-treated samples. Four candidate
      autoantigens were common to both MVL and GII lesions: dihydropyrimidinase-related
      protein 2, fructose-bisphosphate aldolase C, chaperonin-containing T-complex
      polypeptide 1 subunit zeta, and pyruvate kinase isozyme. CONCLUSIONS: Laser
      induced retinal injuries resulted in circulating anti-retinal antibodies that
      were detectable 3 months after the injury. The response appeared to vary with the
      severity of the laser retinal damage. The identification of the candidate
      antigens in this study suggest that this approach may permit future development
      of new diagnostic methods for retinal injuries.

PMID- 22395889
TI  - Effect of treatment on the rate of visual field change in the ocular hypertension
      treatment study observation group.
AB  - PURPOSE: The goal in this study was to compare rates of visual field (VF) change
      before and after the initiation of treatment in participants originally
      randomized to the observation arm of the Ocular Hypertension Treatment Study
      (OHTS). METHODS: We included OHTS participants originally randomized to
      observation and excluded those who reached non-POAG endpoints. VF progression was
      determined using trend analysis. Global and localized rates of VF change were
      calculated based on linear regression over time of mean deviation (MD) and
      threshold sensitivity values for each test location. MD rates (MDR) and pointwise
      linear regression (PLR) analysis were also assessed using six VF tests before and
      after the initiation of treatment. A PLR endpoint was defined as a VF test
      location progressing faster than -0.5 dB/year at P < 0.01. RESULTS: We included
      780 eyes from 432 OHTS participants. Following the initiation of treatment, the
      mean MDR decreased from -0.23 +/- 0.6 to -0.06 +/- 0.5 dB/year (P < 0.01) and the
      number of VF locations reaching a PLR endpoint decreased from 2.13 +/- 6.0 to
      1.00 +/- 4.0 (P < 0.01). The benefit of treatment was significant both among
      participants who did not convert (-0.17 +/- 0.6 vs. -0.01 +/- 0.5 dB/year, P <
      0.01) and among those who converted to glaucoma (-0.51 +/- 0.8 vs. -0.27 +/- 0.7
      dB/year, P < 0.01) based on the OHTS event-based endpoint. CONCLUSIONS: The
      initiation of ocular hypotensive medication among OHTS participants originally
      randomized to observation significantly reduced the velocity of VF progression.

PMID- 22395888
TI  - Hydrocortisone stimulates neurite outgrowth from mouse retinal explants by
      modulating macroglial activity.
AB  - PURPOSE: There is mounting evidence that retinal ganglion cells (RGCs) require a
      complex milieu of trophic factors to enhance cell survival and axon regeneration
      after optic nerve injury. The authors' goal was to examine the contribution of
      components of a combination of hormones, growth factors, steroids, and small
      molecules to creating a regenerative environment and to determine if any of these
      components modulated macroglial behavior to aid in regeneration. METHODS:
      Postnatal day 7 mouse retinal explants embedded in collagen were used as an in
      vitro model of neurite regeneration. Explants were treated with the culture
      supplements fetal bovine serum, N2, and G5 and a mixture of G5 and N2 components,
      designated enhanced N2 (EN2). Explants were evaluated for neurite outgrowth over
      7 days in culture. The effects of each treatment were also evaluated on cultured
      RGCs purified by Thy1 immunopanning. Immunohistochemistry and qPCR analysis were
      used to evaluate differences in gene expression in the explants due to different
      treatments. RESULTS: EN2 stimulated significant neurite outgrowth from explants
      but not from purified RGCs. Elimination of hydrocortisone (HC) from EN2 reduced
      the mean neurites per explant by 37%. EN2-treated explants demonstrated increased
      expression of Gfap, Glul, Glt1, Cntf, Pedf, and VegfA compared with explants
      treated with EN2 without HC. Subsequent experiments showed that increased
      expression of Cntf and Glul was critical to the trophic effect of HC.
      CONCLUSIONS: These data suggest that the HC in EN2 indirectly contributed to
      neurite outgrowth by activating macroglia to produce neurotrophic and
      neuroprotective molecules.

PMID- 22395891
TI  - Altered stability of mRNAs associated with glaucoma progression in human
      trabecular meshwork cells following oxidative stress.
AB  - PURPOSE: The goals of this study were to determine if oxidative stress on human
      trabecular meshwork (HTM) cells influences the stability of key mRNAs containing
      AU rich elements (AREs) known to be associated with glaucoma progression, and if
      the presence of topographic cue alters the stability of these mRNAs. METHODS: HTM
      cells were treated with 300 MUM hydrogen peroxide (H(2)O(2)) for 1 hour in the
      presence of 5 MUg/mL actinomycin D and compared with untreated cells. The
      selected mRNAs (IL-6, IL-8, myocilin, SPARC [secreted protein, acidic and rich in
      cysteine], matrix metalloproteinase [MMP]-3, and MMP-9) from the cells were
      analyzed by using relative quantitative PCR. Immunohistochemistry for Hu antigen
      R (HuR) was performed in addition to Western blots of HuR. HTM cells were also
      grown on topographically patterned surfaces, and IL-6 mRNA was analyzed by
      quantitative PCR. RESULTS: H(2)O(2) increased IL-6 mRNA stability 0.145 (0.095
      0.27) to 0.345 (0.2-0.48) (normalized ratio, median [interquartile range]) (n =
      5), while IL-8 mRNA was increased from 0.565 (0.408-0.6) to 0.775 (0.486-0.873)
      (n = 5). These differences were statistically significant (P = 0.0313, for both
      IL-6 and IL-8; Wilcoxon signed-rank test). The mRNAs of myocilin, SPARC, and MMP
      3, which do not have AREs, were more stable after actinomycin D treatment and
      were not altered with oxidation. Western blot and immunohistochemistry
      demonstrated that H(2)O(2) treatment induces the translocation of HuR from the
      nucleus to the cytoplasm. Nanopatterned surfaces did not alter IL-6 mRNA
      stability. CONCLUSIONS: Oxidative stress stabilizes IL-6 and IL-8 mRNAs
      significantly. The decay of certain mRNAs associated with glaucoma may be altered
      in the trabecular meshwork of glaucoma patients.

PMID- 22395893
TI  - Subthreshold laser treatment versus threshold laser treatment for symptomatic
      retinal arterial macroaneurysm.
AB  - PURPOSE: This study was designed to compare the effects of subthreshold laser
      treatment (STLT) with threshold laser treatment (TLT) in patients affected by
      symptomatic retinal arterial macroaneurism (RAM). METHODS: Patients affected by
      symptomatic RAM, characterized by exudative manifestations involving the fovea
      and best-corrected visual acuity (BCVA) worse than 20/80 Snellen equivalent, were
      recruited. Patients were randomly assigned to STLT or TLT and regularly followed
      up for 12 months. Primary outcome measures were changes in central point
      thickness (CPT) at the end of the follow-up. Secondary outcome measures were
      changes in mean BCVA at the end of the follow-up and identification of postlaser
      alterations. RESULTS: In this single center, randomized, clinical trial, 12
      patients were randomized to STLT and 13 to TLT. CPT in STLT was 332 MUm at
      baseline and changed to 249 MUm at the 12-month examination. CPT in TLT was 341
      MUm and reduced to 226 MUm at the end of the follow-up. BCVA in STLT changed from
      0.72 logMAR to 0.28 logMAR. BCVA in TLT changed from 0.76 logMAR to 0.26 logMAR.
      The statistical analyses revealed a significant difference comparing the baseline
      values for both CPT and BCVA in each subgroup from the third month (P < 0.001).
      No difference was found comparing the two subgroups at any point in time. Three
      eyes (23%) treated with TLT developed an epiretinal membrane with subjective
      metamorphopsia. CONCLUSIONS: This pilot randomized clinical trial shows that both
      STLT and TLT can achieve similar improvements in BCVA and CPT. The lower laser
      energy delivered by STLT can reduce the complication rate.

PMID- 22395894
TI  - In vivo assessment of thickness and reflectivity in a rat outer retinal
      degeneration model with ultrahigh resolution optical coherence tomography.
AB  - PURPOSE: To provide in vivo quantitative assessment of sodium iodate-induced
      retinal damage in a rat model of outer retinal degeneration using ultrahigh
      resolution optical coherence tomography (UHR-OCT). METHODS: Outer retinal
      degeneration was induced in four female Long Evans rats via tail vein injection
      of sodium iodate (40 mg/kg). Changes in the thickness and optical reflectivity of
      individual retinal layers were extracted using a semi-automatic segmentation
      algorithm and were assessed in vivo at 6 hours, days 1, 3, and 7, and up to 3
      months post injection with UHR-OCT. Hematoxylin and eosin (H&E) histology was
      used to confirm the morphologic changes observed in the UHR-OCT images. RESULTS:
      UHR-OCT tomograms showed progressive structural damage in the rat retina over
      time, such as swelling, thinning, complete disintegration of individual retinal
      layers, and clustering of highly reflective cellular debris. Photoreceptor
      swelling was observed 6 hours after injection of sodium iodate, followed by
      progressive structural decomposition of the outer retina. At 3 months post
      injection, the outer retina was completely disintegrated, and the inner nuclear
      layer (INL) was in direct contact with the choroid. Changes in the reflectivity
      of individual retinal layers were observed over time and correlated well with the
      morphologic changes. CONCLUSIONS: UHR-OCT permits in vivo, noninvasive,
      longitudinal, quantitative assessment of the progressive changes in retinal
      morphology and optical reflectivity in a sodium iodate rodent model of outer
      retinal degeneration.

PMID- 22395892
TI  - Autosomal recessive retinitis pigmentosa due to ABCA4 mutations: clinical,
      pathologic, and molecular characterization.
AB  - PURPOSE: Autosomal recessive retinitis pigmentosa (ARRP) is a genetically
      heterogeneous condition characterized by progressive loss of retinal
      photoreceptor cells. In order to gain new insights into the pathogenesis of ARRP,
      we evaluated the morphological, biochemical, and gene expression changes in eyes
      from a human donor with ARRP due to mutations in the ABCA4 gene. METHODS: Eyes
      were obtained postmortem from a donor with end-stage retinitis pigmentosa. The
      coding sequences of the RDS, RHO, and ABCA4 genes were screened for disease
      causing mutations. Morphological changes in different regions of the retina were
      examined histologically, and levels of lipofuscin-associated bisretinoids were
      measured. Gene expression was examined in retinal/choroidal tissue using
      microarray analysis, and all parameters were compared to those in unaffected
      control donors. RESULTS: Genetic analysis of the donor's DNA identified two
      mutations in the ABCA4 gene, IVS14+1G > C and Phe1440del1 cT, each on a separate
      allele. Morphological evaluation revealed complete loss of the outer nuclear
      layer, remodeling of the inner retina, loss of retinal vasculature, and regional
      neovascularization. The retinal pigment epithelium and choriocapillaris exhibited
      regional preservation. Microarray analysis revealed loss of photoreceptor cell
      associated transcripts, with preservation of multiple genes expressed
      specifically in inner retinal neurons. CONCLUSIONS: The persistence of
      transcripts expressed by inner retinal neurons suggests that despite significant
      plasticity that occurs during retinal degeneration, bipolar cells and ganglion
      cells remain at least partially differentiated. Findings from this study suggest
      that some forms of therapy currently under investigation may have benefit even in
      advanced retinal degeneration.

PMID- 22395895
TI  - Ischemic cardiac tissue conditioned media induced differentiation of human
      mesenchymal stem cells into early stage cardiomyocytes.
AB  - Mesenchymal stem cells (MSCs) are multipotent, can be easily expanded in culture
      and hence are an attractive therapeutic tool for cardiac repair. MSCs have
      tremendous potential to transdifferentiate to cardiac lineage both in vitro and
      in vivo. The present study examined the differentiation capacity of conditioned
      media derived from ischemic cardiac tissue on human MSCs. Human Bone marrow
      derived MSCs after due characterization by immunocytochemistry and flow cytometry
      for MSC specific markers were induced by culture media derived from ischemic (n =
      13) and non-ischemic (n = 18) human cardiac tissue. Parallel cultures were
      treated with 5-azacytidine (5-azaC), a potent cardiomyogen. MSCs induced with
      ischemic conditioned media formed myotube like structures, expressed sarcomeric
      Troponin I, alpha myosin heavy chain proteins and were positive for cardiac
      specific markers (Nkx2.5, human atrial natriuretic peptide, myosin light chain
      2a, GATA-4) as was observed in 5-azaC treated cells. However, uninduced MSCs as
      well as those induced with non-ischemic cardiac conditioned media still
      maintained the fibroblast morphology even after 3 weeks post-induction.
      Transmission electron microscopic studies of cardiomyocyte-like cells derived
      from MSCs revealed presence of sarcomeric bands but failed to show gap junctions
      and intercalated discs as of adult cardiomyocytes. These findings demonstrate
      that ischemic cardiac conditioned media induces morphological and molecular
      changes in MSCs with cardiac features, but at a primitive stage. Proteomics
      analysis of the ischemic conditioned media revealed differential expression of
      three relevant proteins (C-type lectin superfamily member 13, Testis-specific
      chromodomain protein Y2 and ADP/ATP translocase 1), whose exact role in cardiac
      regeneration needs further analysis.

PMID- 22395896
TI  - Effects of Hypericum montbretti extract on the central nervous system and
      involvement of GABA (A)/Benzodiazepine receptors in its pharmacological activity.
AB  - The present study was undertaken to investigate the putative activity of a
      methanol extract of Hypericum montbretti (Guttiferae) on the central nervous
      system. Rutin (1519 ppm) and quercitrin (784 ppm) were identified as the major
      phenolic compounds in the extract. When administered at 25, 50 and 100 mg/kg
      doses, the extract decreased the total number of head-dipping behaviours
      performed by mice during a hole-board test. Administration of both the extract
      and diazepam (2 mg/kg) reduced spontaneous locomotory activity, potentiated
      hexobarbital (60 mg/kg)-induced sleeping parameters and prevented
      pentylenetetrazole (80 mg/kg)-induced seizures relative to the controls. These
      findings are the first to indicate the sedative and anticonvulsant activities of
      H. montbretti extract. Atropine (2 mg/kg) and naloxone (5 mg/kg) pre-treatment
      did not reverse the sedative effect, indicating that muscarinic and opioidergic
      mechanisms did not contribute to the pharmacological action. However, pre
      treatment with flumazenil (a benzodiazepine receptor antagonist) reversed both
      the sedative and anticonvulsant effects induced by a 100 mg/kg dose of the
      extract, indicating the involvement of the GABA(A)-benzodiazepine receptor
      complex. In conclusion, H. montbretti extract is a novel candidate as a sedative
      and anticonvulsant drug for the treatment of sleep disorders and for the
      prevention of epileptic seizures.

PMID- 22395897
TI  - Shotgun proteomic monitoring of Clostridium acetobutylicum during stationary
      phase of butanol fermentation using xylose and comparison with the exponential
      phase.
AB  - Economically viable production of solvents through acetone-butanol-ethanol (ABE)
      fermentation requires a detailed understanding of Clostridium acetobutylicum.
      This study focuses on the proteomic profiling of C. acetobutylicum ATCC 824 from
      the stationary phase of ABE fermentation using xylose and compares with the
      exponential growth by shotgun proteomics approach. Comparative proteomic analysis
      revealed 22.9% of the C. acetobutylicum genome and 18.6% was found to be common
      in both exponential and stationary phases. The proteomic profile of C.
      acetobutylicum changed during the ABE fermentation such that 17 proteins were
      significantly differentially expressed between the two phases. Specifically, the
      expression of five proteins namely, CAC2873, CAP0164, CAP0165, CAC3298, and
      CAC1742 involved in the solvent production pathway were found to be significantly
      lower in the stationary phase compared to the exponential growth. Similarly, the
      expression of fucose isomerase (CAC2610), xylulose kinase (CAC2612), and a
      putative uncharacterized protein (CAC2611) involved in the xylose utilization
      pathway were also significantly lower in the stationary phase. These findings
      provide an insight into the metabolic behavior of C. acetobutylicum between
      different phases of ABE fermentation using xylose.

PMID- 22395898
TI  - Characteristics of bifunctional acidic endoglucanase (Cel5B) from Gloeophyllum
      trabeum.
AB  - The endoglucanase (Cel5B) from the filamentous fungus Gloeophyllum trabeum was
      cloned and expressed without a signal peptide, and alanine residue 22 converted
      to glutamine in Pichia pastoris GS115. The DNA sequence of Cel5B had an open
      reading frame of 1,077 bp, encoding a protein of 359 amino acid residues with a
      molecular weight of 47 kDa. On the basis of sequence similarity, Cel5B displayed
      active site residues at Glu-175 and Glu-287. Both residues lost full hydrolytic
      activity when replaced with alanine through point mutation. The purified
      recombinant Cel5B showed very high specific activity, about 80- to 1,000-fold and
      13- to 70-fold in comparison with other endoglucanases and cellobiohydrolase, on
      carboxymethylcellulose and filter paper, respectively, at pH 3.5 and 55 degrees
      C. Cel5B displayed bifunctional characteristics under acidic conditions. The
      kinetic properties of the enzyme determined using a Lineweaver-Burk plot
      indicated that Cel5B is a catalytically efficient cellulolytic enzyme. These
      results suggest that Cel5B has high bifunctional endo- and exoglucanase activity
      under acidic conditions and is a good candidate for bioconversion of
      lignocellulose.

PMID- 22395899
TI  - Intensification of beta-poly(L: -malic acid) production by Aureobasidium
      pullulans ipe-1 in the late exponential growth phase.
AB  - beta-Poly(malic acid) (PMLA) has attracted industrial interest because this
      polyester can be used as a prodrug or for drug delivery systems. In PMLA
      production by Aureobasidium pullulans ipe-1, it was found that PLMA production
      was associated with cell growth in the early exponential growth phase and
      dissociated from cell growth in the late exponential growth phase. To enhance
      PMLA production in the late phase, different fermentation modes and strategies
      for controlling culture redox potential (CRP) were studied. The results showed
      that high concentrations of produced PMLA (above 40 g/l) not only inhibited PMLA
      production, but also was detrimental to cell growth. Moreover, when CRP increased
      from 57 to 100 mV in the late exponential growth phase, the lack of reducing
      power in the broth also decreased PMLA productivity. PMLA productivity could be
      enhanced by repeated-batch culture to maintain cell growth in the exponential
      growth phase, or by cell-recycle culture with membrane to remove the produced
      PMLA, or by maintaining CRP below 70 mV no matter which kind of fermentation mode
      was adopted. Repeated-batch culture afforded a high PMLA concentration (up to
      63.2 g/l) with a productivity of 1.15 g l(-1) h(-1). Cell-recycle culture also
      confirmed that PMLA production by the strain ipe-1 was associated with cell
      growth.

PMID- 22395900
TI  - [Diagnostic imaging and visualization of radiation treatment effects in soft
      tissue sarcomas].
AB  - Soft tissue sarcomas are rare malignant neoplasms accounting for only 1% of
      malignant tumors in adults. Complete surgical resection of tumors is the key to
      therapeutic success. Indications for adjuvant radiation therapy vary according to
      the lesion grade. Comprehensive diagnostic imaging significantly contributes to
      successful preoperative planning procedures. Besides morphological imaging,
      functional imaging strategies will have an increasing impact on individual risk
      assessment and contribute to optimized, non-invasive treatment response
      monitoring.

PMID- 22395901
TI  - A simple synthesis of N-perfluoroacylated and N-acylated glycals of neuraminic
      acid with a cyclic aminic substituent at the 4alpha position as possible
      inhibitors of sialidases.
AB  - A simple protocol for the synthesis of N-perfluoroacylated and N-acylated glycals
      of neuraminic acid, with a secondary cyclic amine (morpholine or piperidine) at
      the 4alpha position, has been set-up, starting from peracetylated N
      acetylneuraminic acid methyl ester that undergoes, sequentially to its direct N
      transacylation followed by a C-4 amination, a beta-elimination, and a selective
      hydrolysis of the ester functions, without affecting the sensitive perfluorinated
      amide.

PMID- 22395902
TI  - Developing a high-quality scoring function for membrane protein structures based
      on specific inter-residue interactions.
AB  - Membrane proteins are of particular biological and pharmaceutical importance, and
      computational modeling and structure prediction approaches play an important role
      in studies of membrane proteins. Developing an accurate model quality assessment
      program is of significance to the structure prediction of membrane proteins. Few
      such programs are proposed that can be applied to a broad range of membrane
      protein classes and perform with high accuracy. We developed a new model scoring
      function Interaction-based Quality assessment (IQ), based on the analysis of four
      types of inter-residue interactions within the transmembrane domains of helical
      membrane proteins. This function was tested using three high-quality model sets:
      all 206 models of GPCR Dock 2008, all 284 models of GPCR Dock 2010, and all 92
      helical membrane protein models of the HOMEP set. For all three sets, the scoring
      function can select the native structures among all of the models with the
      success rates of 93, 85, and 100% respectively. For comparison, these three model
      sets were also adopted for a recently published model assessment program for
      membrane protein structures, ProQM, which gave the success rates of 85, 79, and
      92% separately. These results suggested that IQ outperforms ProQM when only the
      transmembrane regions of the models are considered. This scoring function should
      be useful for the computational modeling of membrane proteins.

PMID- 22395903
TI  - A reverse combination of structure-based and ligand-based strategies for virtual
      screening.
AB  - A new approach is presented that combines structure- and ligand-based virtual
      screening in a reverse way. Opposite to the majority of the methods, a docking
      protocol is first employed to prioritize small ligands ("fragments") that are
      subsequently used as queries to search for similar larger ligands in a database.
      For a given chemical library, a three-step strategy is followed consisting of (1)
      contraction into a representative, non-redundant, set of fragments, (2) selection
      of the three best-scoring fragments docking into a given macromolecular target
      site, and (3) expansion of the fragments' structures back into ligands by using
      them as queries to search the library by means of fingerprint descriptions and
      similarity criteria. We tested the performance of this approach on a collection
      of fragments and ligands found in the ZINC database and the directory of useful
      decoys, and compared the results with those obtained using a standard docking
      protocol. The new method provided better overall results and was several times
      faster. We also studied the chemical diversity that both methods cover using an
      in-house compound library and concluded that the novel approach performs
      similarly but at a much smaller computational cost.

PMID- 22395904
TI  - Oxygen supply in Bacillus thuringiensis fermentations: bringing new insights on
      their impact on sporulation and delta-endotoxin production.
AB  - The growth kinetics, sporulation, and toxicity of Bacillus thuringiensis var.
      israelensis were evaluated through the analysis of batch cultures with different
      dissolved oxygen (DO) profiles. Firstly, DO was maintained constant at 5%, 20%,
      or 50% throughout fermentation in order to identify the most suitable one to
      improve the main process parameters. Higher biomass concentration, cell
      productivity, and cell yield based on glucose were obtained with 50% DO. The
      higher aeration level also resulted in higher spore counts and markedly improved
      the toxic activity of the fermentation broth, which was 9-fold greater than that
      obtained with 5% DO (LC(50) of 39 and 329 mg/L, respectively). Subsequently,
      using a two-stage oxygen supply strategy, DO was kept at 50% during the
      vegetative and transition phases until the maximum cell concentration was
      achieved. Then, DO was changed to 0%, 5%, 20%, or 100% throughout sporulation and
      cell lysis phases. The interruption of oxygen supply strongly reduced the spore
      production and thoroughly repressed the toxin synthesis. On the contrary, when DO
      was raised to 100% of saturation, toxic activity increased approximately four
      times (LC(50) of 8.2 mg/L) in comparison with the mean values reached with lower
      DO levels, even though spore counts were lower than that from the 50% DO assay.
      When pure oxygen was used instead of normal air, it was possible to obtain 70% of
      the total biomass concentration achieved in the air assays; however, cultures did
      not sporulate and the toxin synthesis was consequently suppressed.

PMID- 22395905
TI  - Insulin-producing cells from human adipose tissue-derived mesenchymal stem cells
      detected by atomic force microscope.
AB  - We successfully differentiated human adipose tissue-derived mesenchymal stem
      cells (haMSCs) into insulin-producing cells (IPCs) in vitro and did not use any
      insulin which might be absorbed by cells during in vitro culture. Expression of
      insulin gene was massively increased by 28,000-fold at day 12 compared with
      haMSCs (P < 0.05). IPCs could secrete insulin after glucose was stimulated. The
      higher the concentration of glucose, the more production of insulin was noted. We
      reported AFM images of IPCs for the first time. AFM images showed that the sizes
      of cells were similar to each other, and all IPC surface had a porous structure
      in the cytoplasm area. In sugar-free group, the size of holes was similar
      (diameter, 1,086.98 +/- 156.70 nm; depth, 185.22 +/- 52.14 nm). In higher sugar
      stimulated group, there were more holes with bigger diameter and smaller depth.
      (diameter, 3,183.65 +/- 2,229.18 nm; depth 109.42 +/- 56.26 nm, P < 0.05). We
      found that the hole diameter and depth could change with the concentration of
      glucose in media. Concurrently, laser scanning confocal microscopy images
      indicated that cortical actin network beneath plasma membrane in IPCs was dense
      and continuous. After glucose stimulation, we found the actin web depolymerized
      and became discontinuous in IPCs. We speculated that diameter augmentation of
      holes located in the cytoplasm area in IPCs was one manifestation of excytosis
      increase.

PMID- 22395906
TI  - Factors influencing the degradation of garbage in methanogenic bioreactors and
      impacts on biogas formation.
AB  - Anaerobic digestion of garbage is attracting much attention because of its
      application in waste volume reduction and the recovery of biogas for use as an
      energy source. In this review, various factors influencing the degradation of
      garbage and the production of biogas are discussed. The surface hydrophobicity
      and porosity of supporting materials are important factors in retaining
      microorganisms such as aceticlastic methanogens and in attaining a higher
      degradation of garbage and a higher production of biogas. Ammonia concentration,
      changes in environmental parameters such as temperature and pH, and adaptation of
      microbial community to ammonia have been related to ammonia inhibition. The
      effects of drawing electrons from the methanogenic community and donating
      electrons into the methanogenic community on methane production have been shown
      in microbial fuel cells and bioelectrochemical reactors. The influences of trace
      elements, phase separation, and co-digestion are also summarized in this review.

PMID- 22395907
TI  - Lactococcus lactis expressing food-grade beta-galactosidase alleviates lactose
      intolerance symptoms in post-weaning Balb/c mice.
AB  - The endogenous beta-galactosidase expressed in intestinal microbes is
      demonstrated to help humans in lactose usage, and treatment associated with the
      promotion of beneficial microorganism in the gut is correlated with lactose
      tolerance. From this point, a kind of recombinant live beta-galactosidase
      delivery system using food-grade protein expression techniques and selected
      probiotics as vehicle was promoted by us for the purpose of application in
      lactose intolerance subjects. Previously, a recombinant Lactococcus lactis MG1363
      strain expressing food-grade beta-galactosidase, the L. lactis MG1363/FGZW, was
      successfully constructed and evaluated in vitro. This study was conducted to in
      vivo evaluate its efficacy on alleviating lactose intolerance symptoms in post
      weaning Balb/c mice, which were orally administered with 1 * 106 CFU or 1 * 108
      CFU of L. lactis MG1363/FGZW daily for 4 weeks before lactose challenge. In
      comparison with naive mice, the mice administered with L. lactis MG1363/FGZW
      showed significant alleviation of diarrhea symptoms in less total feces weight
      within 6 h post-challenge and suppressed intestinal motility after lactose
      challenge, although there was no significant increase of beta-galactosidase
      activity in small intestine. The alleviation also correlated with higher species
      abundance, more Bifidobacterium colonization, and stronger colonization
      resistance in mice intestinal microflora. Therefore, this recombinant L. lactis
      strain effectively alleviated diarrhea symptom induced by lactose uptake in
      lactose intolerance model mice with the probable mechanism of promotion of lactic
      acid bacteria to differentiate and predominantly colonize in gut microbial
      community, thus making it a promising probiotic for lactose intolerance subjects.

PMID- 22395908
TI  - Transcriptional analysis of Pleurotus ostreatus laccase genes.
AB  - Fungal laccases (p-diphenol:oxygen oxidoreductase; EC 1.10.3.2) are multi-copper
      containing oxidases that catalyse the oxidation of a great variety of phenolic
      compounds and aromatic amines through simultaneous reduction of molecular oxygen
      to water. Fungi generally produce several laccase isoenzymes encoded by complex
      multi-gene families. The Pleurotus ostreatus genome encodes 11 putative laccase
      coding genes, and only six different laccase isoenzymes have been isolated and
      characterised so far. Laccase expression was found to be regulated by culture
      conditions and developmental stages even if the redundancy of these genes still
      raises the question about their respective functions in vivo. In this context,
      laccase transcript profiling analysis has been used to unravel the physiological
      role played by the different isoforms produced by P. ostreatus. Even if reported
      results depict a complex picture of the transcriptional responses exhibited by
      the analysed laccase genes, they were allowed to speculate on the isoform role in
      vivo. Among the produced laccases, LACC10 (POXC) seems to play a major role
      during vegetative growth, since its transcription is downregulated when the
      fungus starts the fructification process. Furthermore, a new tessera has been
      added to the puzzling mosaic of the heterodimeric laccase LACC2 (POXA3). LACC2
      small subunit seems to play an additional physiological role during
      fructification, beside that of LACC2 complex activation/stabilisation.

PMID- 22395909
TI  - Fluorescence imaging and targeted distribution of bacterial magnetic particles in
      nude mice.
AB  - Bacterial magnetic particles (BMPs) are of interest as potential carriers of
      bioactive macromolecules, drugs, or liposomes. In this study, a high-pressure
      homogenizer was used to disrupt Magnetospirillum gryphiswaldense strain MSR-1
      cells, and BMPs were purified. BMPs were labeled with fluorescence reagent 1,1'
      dioctadecyl-3,3,3',3'-tetramethylindocarbocianin perchlorate (DiI) and injected
      into the tail vein of BALB/c nude mice. Distribution of fluorescence signals of
      DiI-BMPs in vivo was examined using a whole-body fluorescence imaging system. The
      result showed that fluorescence signals were detected in liver, stomach,
      intestine, lungs, and spleen. However, transmission electron microscopy of
      ultrathin sections indicated that BMPs were mainly present in liver and lungs,
      but not in the other organs. BMPs could be useful as carriers for targeted drug
      therapy of diseases of the liver or lung.

PMID- 22395911
TI  - An efficient transformation method for Bacillus subtilis DB104.
AB  - Bacillus subtilis strains are used for extracellular expression of enzymes (i.e.,
      proteases, lipases, and cellulases) which are often engineered by directed
      evolution for industrial applications. B. subtilis DB104 represents an attractive
      directed evolution host since it has a low proteolytic activity and efficient
      secretion. B. subtilis DB104 is hampered like many other Bacillus strains by
      insufficient transformation efficiencies (<=10(3) transformants/MUg DNA). After
      investigating five physical and chemical transformation protocols, a novel
      natural competent transformation protocol was established for B. subtilis DB104
      by optimizing growth conditions and histidine concentration during competence
      development, implementing an additional incubation step in the competence
      development phase and a recovery step during the transformation procedure. In
      addition, the influence of the amount and size of the transformed plasmid DNA on
      transformation efficiency was investigated. The natural competence protocol is
      "easy" in handling and allows for the first time to generate large libraries (1.5
      * 10(5) transformants/MUg plasmid DNA) in B. subtilis DB104 without requiring
      microgram amounts of DNA.

PMID- 22395910
TI  - Isolation and lipid degradation profile of Raoultella planticola strain 232-2
      capable of efficiently catabolizing edible oils under acidic conditions.
AB  - The lipids (fats and oils) degradation capabilities of soil microorganisms were
      investigated for possible application in treatment of lipids-contaminated
      wastewater. We isolated a strain of the bacterium Raoultella planticola strain
      232-2 that is capable of efficiently catabolizing lipids under acidic conditions
      such as in grease traps in restaurants and food processing plants. The strain 232
      2 efficiently catabolized a mixture (mixed lipids) of commercial vegetable oil,
      lard, and beef tallow (1:1:1, w/w/w) at 20-35  degrees C, pH 3-9, and 1,000-5,000
      ppm lipid content. Highly effective degradation rate was observed at 35  degrees
      C and pH 4.0, and the 24-h degradation rate was 62.5 +/- 10.5 % for 3,000 ppm
      mixed lipids. The 24-h degradation rate for 3,000 ppm commercial vegetable oil,
      lard, beef tallow, mixed lipids, and oleic acid was 71.8 %, 58.7 %, 56.1 %, 55.3
      +/- 8.5 %, and 91.9 % at pH 4 and 30  degrees C, respectively. R. planticola
      NBRC14939 (type strain) was also able to efficiently catabolize the lipids after
      repeated subculturing. The composition of the culture medium strongly influenced
      the degradation efficiency, with yeast extract supporting more complete
      dissimilation than BactoPeptone or beef extract. The acid tolerance of strain 232
      2 is proposed to result from neutralization of the culture medium by urease
      mediated decomposition of urea to NH(3). The rate of lipids degradation increased
      with the rates of neutralization and cell growth. Efficient lipids degradation
      using strain 232-2 has been achieved in the batch treatment of a restaurant
      wastewater.

PMID- 22395912
TI  - Ethanol production from concentrated food waste hydrolysates with yeast cells
      immobilized on corn stalk.
AB  - The aim of the present study was to examine ethanol production from concentrated
      food waste hydrolysates using whole cells of S. cerevisiae immobilized on corn
      stalks. In order to improve cell immobilization efficiency, biological
      modification of the carrier was carried out by cellulase hydrolysis. The results
      show that proper modification of the carrier with cellulase hydrolysis was
      suitable for cell immobilization. The mechanism proposed, cellulase hydrolysis,
      not only increased the immobilized cell concentration, but also disrupted the
      sleek surface to become rough and porous, which enhanced ethanol production. In
      batch fermentation with an initial reducing sugar concentration of 202.64 +/-
      1.86 g/l, an optimal ethanol concentration of 87.91 +/- 1.98 g/l was obtained
      using a modified corn stalk-immobilized cell system. The ethanol concentration
      produced by the immobilized cells was 6.9% higher than that produced by the free
      cells. Ethanol production in the 14th cycle repeated batch fermentation
      demonstrated the enhanced stability of the immobilized yeast cells. Under
      continuous fermentation in an immobilized cell reactor, the maximum ethanol
      concentration of 84.85 g/l, and the highest ethanol yield of 0.43 g/g (of
      reducing sugar) were achieved at hydraulic retention time (HRT) of 3.10 h,
      whereas the maximum volumetric ethanol productivity of 43.54 g/l/h was observed
      at a HRT of 1.55 h.

PMID- 22395913
TI  - Molecular detection of Torque teno mini virus (TTMV) in China.
AB  - In this study, 176 serum specimens were collected from hospitalized
      cardiovascular diseases patients in Shanghai, China. 140 samples (79.5%) were
      positive with the primers located in non-coding region, and 30 samples (17.04%)
      were identified to be positive with group-specific primers. Of the 30 samples, 9
      (5.11%) were classified to group 1, 23 (13.07%) were clustered to group 2, and 3
      belonged to group 3. Five samples were confirmed to be dual infection with
      different groups of TTMV, and no sample was found to be infected with groups 4-6.

PMID- 22395914
TI  - Comparative [corrected] codon usage between the three main viruses in pestivirus
      genus and their natural susceptible livestock.
AB  - Classical swine fever virus, bovine viral diarrhea virus (BVDV), and border
      disease virus can cause serious livestock diseases. The relative synonymous codon
      usage value, the "effective number of codons" (ENC), the ratio of K(s) value to
      K(a) value and the principle component analysis were employed to analyze the
      genetic characteristics of open reading frame (ORF) and the four genes (the
      N(pro), Erns, E1, E2 genes) of the three viruses and the relationship of codon
      usage pattern between each virus and its most common host. The amount of under
      represented codons is larger than the amount of over-represented ones in ORFs or
      the four genes of the three viruses. The ENC value and the ratio of K(s)/K(a) for
      each gene show that mutation pressure plays a role in their evolutional
      processes. In addition, the evidence that selection from the natural host might
      influences the codon usage patterns of virus is found in the differences of codon
      usage patterns of ORF and Erns gene of BVDV strain ZM-95 isolated from domestic
      pig and those of the rest of BVDV strains isolated from cattle. These results
      indicate that although a strong mutation pressure from the three pestiviruses
      takes part in their evolutional processes by the alternation of synonymous
      codons, translation selection from the susceptible livestock on some genes should
      not be ignored. The codon usage pattern of the three pestiviruses is a result
      caused by the equilibrium of mutation pressure from virus and translation
      selection from its host.

PMID- 22395915
TI  - Environmental effects in Kelvin force microscopy of modified diamond surfaces.
AB  - We have explored the effects of atmospheric environment on Kelvin force
      microscopy (KFM) measurements of potential difference between different regions
      of test polycrystalline diamond surfaces. The diamond films were deposited by
      microwave plasma-assisted chemical vapor deposition, which naturally produces
      hydrogen terminations on the surface of the films formed. Selected regions were
      patterned by electron-beam lithography and chemical terminations of oxygen or
      fluorine were created by exposure to an oxygen or fluorine plasma source. For KFM
      imaging, the samples were mounted in a hood with a constant flow of helium gas.
      Successive images were taken over a 5-h period showing the effect of the
      environment on KFM imaging. We conclude that the helium flow removes water
      molecules adsorbed on the surface of the samples, resulting in differences in
      surface potential between adjacent regions. The degree of water removal is
      different for surfaces with different terminations. The results highlight the
      importance of taking into account the atmospheric environment when carrying out
      KFM analysis.

PMID- 22395916
TI  - Letter regarding the article by Vismara et al published in Int J Artif Organs
      2011; 34(4): 383-391.

PMID- 22395917
TI  - Modulation of bovine chondrocyte metabolism by free periosteal grafts in vitro.
AB  - PURPOSE: Autologous chondrocyte transplantation (ACT) is an established method in
      cartilage repair. Although long-term results show durable repair of isolated
      cartilage defects, some problems still remain. Since hypertrophy of the
      transplanted periosteum is a common problem, alternatives for periosteum are in
      demand. Periosteal grafts have been reported to stimulate neochondrogenesis via
      paracrine effects. The objective of this study was to evaluate the modulation of
      chondrocyte metabolism by periosteal grafts in vitro. METHODS: Periosteal
      explants and articular chondrocytes obtained from slaughtered adult cattle were
      co-cultured in a newly established perfusion system. The experimental groups
      were: 1. monocultured chondrocytes; 2. chondrocytes cultured with synovial
      supernatants; 3. chondrocytes cultured with periosteal supernatants; 4.
      chondrocytes co-cultured with periosteal explants. RESULTS: Chondrocyte
      proliferation, evaluated by measuring total DNA content, was prolongated by
      periosteal and synovial explants. Immunocytochemical staining of collagen type II
      was stronger in monoculture than in co-culture. Protein biosynthetic activity
      estimated by [3H]-proline incorporation, as well as extracellular matrix
      deposition for collagen type II, were reduced by periosteal and synovial
      explants. Additionally, co-culturing led to a decrease in aggrecan synthesis and
      release. The inhibiting effects were significantly stronger when cellular
      chondrocyte-periosteal cross-talk was made possible via paracrine effects.
      CONCLUSIONS: The results of our study suggest a catabolic effect of periosteal
      explants on isolated chondrocytes in vitro. Further investigations are necessary
      whether periosteum in ACT is dispensable.

PMID- 22395918
TI  - Successful replacement of a detached pedestal during support with Jarvik 2000.
AB  - Infection in patients supported with left ventricular assist devices (LVAD) is
      common and it can limit widespread implantation of mechanical assistance as
      destination therapy (DT). The infection-resistance power delivery system could
      improve longevity and quality of life. The Jarvik 2000 (Jarvik Heart, New York,
      NY, USA) driveline design showed a prolonged infection-free survival and a better
      quality of life compared to those patients supported with traditional LVAD with
      an abdominal cable. We report a singular driveline complication in a 71-year-old
      patient supported with a Jarvik 2000. A new retroauricular pedestal was
      successfully repositioned after the detachement of the first one.

PMID- 22395919
TI  - Assessment of dialysis adequacy guidelines implementation in a developing
      country.
AB  - Dialysis adequacy has been shown to have a significant impact on patient
      survival, but there are few data concerning the adequacy of the delivered
      hemodialysis dose in developing countries. To describe the level of
      implementation of dialysis practice guidelines in a dialysis center in Morocco,
      we retrospectively reviewed our 1-year experience of managing chronic
      hemodialysis patients (CHP), from May 2009 to May 2010. Demographic and
      biochemical data were collected, and the percentage of patients achieving targets
      recommended by the NKF-KDOQI guidelines were calculated. Our data suggests that
      dialysis units in a developing country can achieve current guidelines targets for
      dialysis adequacy, however, our results are not generalizable to all dialysis
      centers in Morocco.

PMID- 22395920
TI  - Prophylactic treatment with alkaline phosphatase in cardiac surgery induces
      endogenous alkaline phosphatase release.
AB  - INTRODUCTION: Laboratory and clinical data have implicated endotoxin as an
      important factor in the inflammatory response to cardiopulmonary bypass. We
      assessed the effects of the administration of bovine intestinal alkaline
      phosphatase (bIAP), an endotoxin detoxifier, on alkaline phosphatase levels in
      patients undergoing coronary artery bypass grafting. METHODS: A total of 63
      patients undergoing coronary artery bypass grafting were enrolled and
      prospectively randomized. Bovine intestinal alkaline phosphatase (n=32) or
      placebo (n=31) was administered as an intravenous bolus followed by continuous
      infusion for 36 hours. The primary endpoint was to evaluate alkaline phosphatase
      levels in both groups and to find out if administration of bIAP to patients
      undergoing CABG would lead to endogenous alkaline phosphatase release. RESULTS:
      No significant adverse effects were identified in either group. In all the 32
      patients of the bIAP-treated group, we found an initial rise of plasma alkaline
      phosphatase levels due to bolus administration (464.27+/-176.17 IU/L). A
      significant increase of plasma alkaline phosphatase at 4-6 hours postoperatively
      was observed (354.97+/-95.00 IU/L) as well. Using LHA inhibition, it was shown
      that this second peak was caused by the generation of tissue non specific
      alkaline phosphatase (TNSALP-type alkaline phosphatase). CONCLUSIONS: Intravenous
      bolus administration plus 8 hours continuous infusion of alkaline phosphatase in
      patients undergoing coronary artery bypass grafting with cardiopulmonary bypass
      results in endogenous alkaline phosphatase release. This endogenous alkaline
      phosphatase may play a role in the immune defense system.

PMID- 22395921
TI  - The Mountain Meadows Massacre and "poisoned springs": scientific testing of the
      more recent, anthrax theory.
AB  - It has been recorded that one of the possible causes that eventually escalated
      into the 1857 manslaughter at Mountain Meadows in Southern Utah was the poisoning
      of an open spring by the Fancher-Baker party as they crossed the Utah territory
      on their way from Arkansas to California. Historical accounts report that a
      number of cattle died, followed by human casualties from those that came in
      contact with the dead animals. Even after the Arkansas party departed, animals
      continued to perish and people were still afflicted by some unknown plague.
      Proctor Hancock Robison, a local 14-year-old boy, died shortly after skinning one
      of the "poisoned" cows. A careful review of the historical records, along with
      the more recent scientific literature, seems to exclude the likelihood of actual
      poisoning in favor of a more recent theory that would point to the bacterium
      Bacillus anthracis as the possible cause of human and animal deaths. In order to
      test this hypothesis, Proctor's remains were exhumed, identified through
      mitochondrial DNA analysis, and tested for the presence of anthrax spores.
      Although preliminary testing of remains and soil was negative, description of the
      clinical conditions that affected Proctor and other individuals does not
      completely rule out the hypothesis of death by anthrax.

PMID- 22395922
TI  - Nonterrorist suicides using hand grenades on the territory of the Autonomous
      Province of Vojvodina, Serbia, from 1990 to 2009.
AB  - Suicides using hand grenades are very rare. The aim of this retrospective study
      was to evaluate the cases of nonterrorist suicides using hand grenades according
      to the number of cases per year, sex, age categories, season of the year, day of
      the week, ethanol blood level, type of hand grenade, pattern of injuries, risk
      factors, and suicide place over a 20-year period, from 1990 to 2009 in Vojvodina,
      Serbia. The total number of the cases in this period was 81, with the highest
      number of cases in 1997 and 2002. Twelwe victims were part of six double
      suicides, where one grenade was used to commit suicide to both victims. The
      results highlighted male predominance of the victims, sober state, the use of
      military hand grenades (M75 and M52 type), posttraumatic stress disorder due to
      participation in military clashes as the main risk factor, and countryside as the
      place of suicide.

PMID- 22395924
TI  - Action plans for patients with chronic obstructive pulmonary disease.

PMID- 22395923
TI  - Glasgow supported self-management trial (GSuST) for patients with moderate to
      severe COPD: randomised controlled trial.
AB  - OBJECTIVE: To determine whether supported self management in chronic obstructive
      pulmonary disease (COPD) can reduce hospital readmissions in the United Kingdom.
      DESIGN: Randomised controlled trial. SETTING: Community based intervention in the
      west of Scotland. PARTICIPANTS: Patients admitted to hospital with acute
      exacerbation of COPD. INTERVENTION: Participants in the intervention group were
      trained to detect and treat exacerbations promptly, with ongoing support for 12
      months. MAIN OUTCOME MEASURES: The primary outcome was hospital readmissions and
      deaths due to COPD assessed by record linkage of Scottish Morbidity Records;
      health related quality of life measures were secondary outcomes. RESULTS: 464
      patients were randomised, stratified by age, sex, per cent predicted forced
      expiratory volume in 1 second, recent pulmonary rehabilitation attendance,
      smoking status, deprivation category of area of residence, and previous COPD
      admissions. No difference was found in COPD admissions or death (111/232 (48%) v
      108/232 (47%); hazard ratio 1.05, 95% confidence interval 0.80 to 1.38). Return
      of health related quality of life questionnaires was poor (n=265; 57%), so that
      no useful conclusions could be made from these data. Pre-planned subgroup
      analysis showed no differential benefit in the primary outcome relating to
      disease severity or demographic variables. In an exploratory analysis, 42%
      (75/150) of patients in the intervention group were classified as successful self
      managers at study exit, from review of appropriateness of use of self management
      therapy. Predictors of successful self management on stepwise regression were
      younger age (P=0.012) and living with others (P=0.010). COPD readmissions/deaths
      were reduced in successful self managers compared with unsuccessful self managers
      (20/75 (27%) v 51/105 (49%); hazard ratio 0.44, 0.25 to 0.76; P=0.003).
      CONCLUSION: Supported self management had no effect on time to first readmission
      or death with COPD. Exploratory subgroup analysis identified a minority of
      participants who learnt to self manage; this group had a significantly reduced
      risk of COPD readmission, were younger, and were more likely to be living with
      others. TRIAL REGISTRATION: Clinical trials NCT 00706303.

PMID- 22395925
TI  - Childhood cough.

PMID- 22395926
TI  - CDKN2A might be better than telomere length in determining individual health
      status.

PMID- 22395927
TI  - For you, commissar, the war is over.

PMID- 22395928
TI  - We must warn women about the risks of untreated, or ineffectively treated,
      epilepsy.

PMID- 22395929
TI  - Social engagement may be as important as cognitive stimulation therapy in
      dementia.

PMID- 22395930
TI  - The media and lay users of health services can improve healthcare delivery in
      poor and middle income countries.

PMID- 22395931
TI  - Support is needed for transdisciplinary communication frameworks in poor and
      middle income countries.

PMID- 22395932
TI  - The tobacco industry is terrified of plain packs.

PMID- 22395933
TI  - Complementary medicine treatments should continue to be evaluated in
      universities.

PMID- 22395934
TI  - Drop the bill--and then what?

PMID- 22395935
TI  - Treatment of varicose veins should not be rationed on the basis of complications
      alone.

PMID- 22395936
TI  - Scarcely credible treatments do not merit university attention.

PMID- 22395938
TI  - Stop digging: CAM modalities have been tested and found wanting.

PMID- 22395939
TI  - Why is alternative medicine alone under censure?

PMID- 22395941
TI  - Gene therapy provides temporary relief in patient with immune disorder.

PMID- 22395940
TI  - Higher prices and plain packaging are part of plan to halve smoking in France by
      2025.

PMID- 22395942
TI  - Doctors and patients complain about severe health restrictions on driving
      licences.

PMID- 22395943
TI  - Mobile "life's end" teams start work in Netherlands.

PMID- 22395944
TI  - Association of antibiotics with status epilepticus.
AB  - The objective of this study is to evaluate clinical picture, radiological
      findings and response to treatment in patients with antibiotic associated status
      epilepticus (SE). In a retrospective review, 12 out of 117 (10%) patients with SE
      had temporal association with antibiotic administration. Their medical history,
      clinical findings, and duration and type of SE were recorded. Serum chemistry,
      blood counts, cranial MRI, EEG and CSF examination were carried out. The
      offending antibiotics were withdrawn and the patients were treated with
      phenytoin, lorazepam, sodium valproate or midazolam. The response to treatment
      was recorded and death during hospital stay noted. The median age of the patients
      was 36 (18 and 74) years and 5 were females. Eight patients had convulsive and
      four nonconvulsive SE. The median duration of status was 12 h. The antibiotics
      related to SE included intravenous cephalosporin (ceftazidime 5, amoxyclavulenic
      acid 2, piperacillin 2, cefepime 1) and quinolones (levofloxacin 3, ofloxacin 1,
      ciprofloxacin 2) in isolation or in combinations. Five patients had hepatic
      (41.7%) and 6 (50%) renal failure; the later received higher than the recommended
      dose of antibiotics. Cranial MRI was abnormal in 7 out of 9 (77.8%) patients that
      include cortical lesion in one, corticosubcortical in three and subcortical in
      three. SE responded to first antiepileptic drug in four and to second in five
      patients. Three patients (25%) had refractory SE. Eight (66.7%) patients died and
      death was related to SE in 2 patients. 10% SE patients may be related to
      antibiotics. Hence the antibiotic should be carefully chosen in patients with
      hepatic and renal failure, and the dose should be modified.

PMID- 22395946
TI  - A study of factors associated with cerebral venous thrombosis.
AB  - Cerebral venous thrombosis (CVT) is an uncommon but important cause of stroke.
      Since there are few number of studies about the factors associated with CVT, we
      aimed to perform a study on Iranian patients, during a 12-year period (1997-2010)
      and assessed the risk factors, mortality rate, symptoms and signs, imaging and
      seasonal distribution. This study was a retrospective cross sectional study
      conducted in Rasul-e-Akram Hospital of Tehran University of Medical Sciences. The
      hospital is a referral neurology center for west, south and east parts of the
      capital city. The patients' data were extracted from the documents and entered to
      a self-designed checklist including probable risk factors, sequels, involved
      venous and also demographic characteristics. From 62 patients, 85.5% of the
      patients were female. Most of the patients were between 25 and 35 years old.
      Superior sagittal sinus was involved in 35 patients. Generalized seizure in the
      expired group (7 patients) was significantly more than the alive group (P =
      0.017). There was a significant relationship between intracranial hemorrhage and
      mortality rate and between the site of thrombosis and level of consciousness.
      There was also a significant relationship between fasting and pregnancy with
      seizure in these patients. Although most of the patients presented in spring and
      autumn, majority of the expired cases were reported in autumn. This study can
      help defining risk factors, symptoms, and predicting risk factors of seizure in
      patients with CVT. We suggest future studies based on gathering data for meta
      analysis.

PMID- 22395945
TI  - Neonatal hypoxic insult-mediated cholinergic disturbances in the brain stem:
      effect of glucose, oxygen and epinephrine resuscitation.
AB  - Molecular processes regulating cholinergic functions play an important role in
      the control of respiration under neonatal hypoxia. The present study evaluates
      neonatal hypoxic insult-mediated cholinergic alterations and the protective role
      of glucose, oxygen and epinephrine resuscitation. The changes in total
      muscarinic, muscarinic M1, M2, M3 receptors and the enzymes involved in
      acetylcholine metabolism--cholineacetyl transferase and acetylcholine easterase
      in the brain stem were analyzed. Hypoxic stress decreased total muscarinic
      receptors along with a reduction in muscarinic M1, M2 and M3 receptor genes in
      the brain stem. The reduction in acetylcholine metabolism is indicated by the
      down regulated cholineacetyl transferase and up regulated acetylcholine easterase
      expression. These cholinergic disturbances in the brain stem were reversed by
      glucose resuscitation to hypoxic neonates. The adverse effects of immediate
      oxygenation and epinephrine administration were also reported. This has immense
      clinical significance in establishing a proper resuscitation for the management
      of neonatal hypoxia.

PMID- 22395947
TI  - Peripheral blood levels of matrix metalloproteinase-9 predict lesion volume in
      acute stroke.
AB  - Matrix metalloproteinases (MMPs) have been implicated to play an important role
      in the destruction of the extracellular matrix in diseases of the central nervous
      system. This study investigated whether the expression of one of these proteases,
      MMP-9 in blood, is related to the size of human brain infarcts assessed with
      magnetic resonance imaging. Consecutively, twenty-one acute stroke patients were
      included prospectively into our study. In blood samples drawn within 24 h after
      onset, MMP-9 RNA-expression and proteolytic-activity were analyzed by
      quantitative polymerase chain reaction and gelatin zymography, respectively. The
      ischemic lesion volumes in time to peak perfusion maps and diffusion weighted
      imaging were measured morphometrically. RNA-expression levels of MMP-9 in
      peripheral blood mononuclear cells (PBMCs) correlated with the brain infarct
      lesion (TTP-delay 4 s, r = -0.61, p = 0.007; TTP-delay 6 s: r = -0.58, p = 0.012;
      DWI r = -0.47; p = 0.047). Our preliminary results demonstrate that MMP-9 RNA is
      upregulated in PBMCs in proportion to ischemia. These findings suggest that MMP-9
      might contribute to the manifestation of ischemic brain damage. Since MMP-9 is
      upregulated in acute ischemia inhibition of MMP-9 may represent a complementary
      treatment target in acute stroke therapy.

PMID- 22395948
TI  - Situating suicide as an anthropological problem: ethnographic approaches to
      understanding self-harm and self-inflicted death.
AB  - More than a century after Durkheim's sociological classic placed the subject of
      suicide as a concern at the heart of social science, ethnographic, cross-cultural
      analyses of what lie behind people's attempts to take their own lives remain few
      in number. But by highlighting how the ethnographic method privileges a certain
      view of suicidal behaviour, we can go beyond the limited sociological and
      psychological approaches that define the field of 'suicidology' in terms of
      social and psychological 'pathology' to engage with suicide from our informants'
      own points of view-and in so doing cast the problem in a new light and new terms.
      In particular, suicide can be understood as a kind of sociality, as a special
      kind of social relationship, through which people create meaning in their own
      lives. In this introductory essay we offer an overview of the papers that make up
      this special issue and map out the theoretical opportunities and challenges they
      present.

PMID- 22395949
TI  - Explaining suicide: an afterword.

PMID- 22395950
TI  - Effect of abamectin on root-knot nematodes and tomato yield.
AB  - BACKGROUND: Tomato growers in Shandong Province, China, commonly face heavy root
      knot nematode infestations. Current methods of control include cadusafos and
      methyl bromide (MeBr), but alternative methods are required because of the high
      toxicity of these pesticides and the ecological risk of their use. Therefore,
      abamectin soil applications were evaluated for their potential to control soil
      nematodes in a series of laboratory tests, greenhouse pot experiments and field
      trials. RESULTS: Laboratory tests showed that abamectin exhibited rapid knockdown
      of Meloidogyne incognita, with LC(50) and LC(90) values that were superior to
      those of cadusafos and averaged 7.06 and 21.81 mg L(-1). In the greenhouse pot
      experiment, soil applications of abamectin provided significant M. incognita
      control similar to that provided by cadusafos while maintaining excellent plant
      height and vigour. In the field trials, abamectin exhibited excellent control
      effects to nematodes while giving a higher tomato yield. There was a 19.3-39.0%
      yield increase from the various treatments compared with the control, and the
      best results were obtained from the highest dose of abamectin. CONCLUSION: The
      results of this study demonstrated that abamectin has the potential to be used as
      an effective alternative to MeBr and cadusafos for nematode control in tomato
      production in Shandong Province.

PMID- 22395951
TI  - Bilateral thoracoscopic splanchnicectomy for pain in patients with chronic
      pancreatitis impairs adrenomedullary but not noradrenergic sympathetic function.
AB  - BACKGROUND: Bilateral thoracoscopic splanchnicectomy (BTS) is a well-known
      technique to alleviate intractable pain in patients with chronic pancreatitis.
      BTS not only disrupts afferent fibers from the pancreas that mediate pain but
      also postganglionic sympathetic fibers, which originate in segments T5-T12 and
      which innervate the vasculature of the liver, pancreas, and the adrenal gland.
      The purpose of this study was to assess whether and how BTS affects sympathetic
      noradrenergic and adrenomedullary function in patients with chronic pancreatitis.
      METHODS: Sixteen patients with chronic pancreatitis for at least 1 year underwent
      autonomic function testing before and 6 weeks after BTS for intractable pain.
      Testing was performed during supine rest and during sympathetic stimulation when
      standing. RESULTS: Supine and standing systolic and diastolic blood pressure were
      significantly lower post-BTS compared with pre-BTS (P = 0.001). One patient
      showed orthostatic hypotension after BTS. Baseline plasma norepinephrine levels
      and plasma norepinephrine responses to sympathetic activation during standing
      were not reduced by BTS. In contrast, supine plasma epinephrine levels and
      responses during standing were significantly reduced (P < 0.001). Parasympathetic
      activity was unaffected by BTS as shown by unaltered Valsalva ratio, I-E
      difference, and DeltaHRmax. CONCLUSIONS: BTS for pain relief in patients with
      chronic pancreatitis reduced adrenomedullary function, due to disruption of the
      efferent sympathetic fibers to the adrenal gland. BTS did not affect
      noradrenergic sympathetic activity, although blood pressure was lower after the
      sympathectomy.

PMID- 22395953
TI  - Transgastric small bowel resection with the new multitasking platform
      EndoSAMURAITM for natural orifice transluminal endoscopic surgery.
AB  - BACKGROUND: Recently, natural orifice transluminal endoscopic surgery has been
      introduced using flexible endoscopic technology. Traditional endoscopes lack
      several capabilities that are needed to perform complex surgical procedures
      safely. The purpose of this study was to evaluate the new multitasking platform
      for transgastric small bowel resection including dissection of the mesentery and
      suturing an anastomosis. METHODS: A new prototype of endoscopic multifunctional
      platform, EndoSAMURAITM (ES), was tested. A standardized in vitro setting was
      established with segments of small bowel and an anastomosis was sutured with the
      device and compared with that by stapler (ST) and hand-sewn (HS). Leak pressure
      was measured. In addition, the system was tested in an experimental in vivo
      situation by performing a transgastric small bowel segmental resection under
      general anesthesia. RESULTS: Median time to perform an anastomosis in the bench
      test was 41 min; median leak pressure for the anastomosis by ES was 14 mmHg, by
      ST 25 mmHg, and HS 15 mmHg. For the in vivo study, the median total procedure
      time was 110 min and leak pressure 53 mmHg. These results show that the end-to
      end small bowel anastomosis can be sutured sufficiently. CONCLUSIONS: This study
      has shown that with a multifunctional platform such as the EndoSAMURAITM, the
      majority of complex surgical tasks can be performed if technically independently
      moving instruments can be used via an ergonomic workstation interface that allows
      for laparoscopy-like maneuvers by the operator. Even with the shortcomings of the
      prototype, it was possible to perform an anastomosis of the small bowel of
      acceptable quality within a reasonable time.

PMID- 22395952
TI  - Thoracoscopic esophagectomy in the prone position.
AB  - BACKGROUND: Minimally invasive esophageal surgery has arisen in an attempt to
      reduce the significant complications associated with esophagectomy. Despite
      proposed technical and physiological advantages, the prone position technique has
      not been widely adopted. This article reviews the current status of prone
      thoracoscopic esophagectomy. METHODS: A systematic literature search was
      performed to identify all published clinical studies related to prone
      esophagectomy. Medline, EMBASE and Google Scholar were searched using the
      keywords "prone," "thoracoscopic," and "esophagectomy" to identify articles
      published between January 1994 and September 2010. A critical review of these
      studies is given, and where appropriate the technique is compared to the more
      traditional minimally invasive technique utilising the left lateral decubitus
      position. RESULTS: Twelve articles reporting the outcomes following prone
      thoracoscopic oesophagectomy were tabulated. These studies were all non
      randomised single-centre prospective or retrospective studies of which four
      compared the technique to traditional minimally invasive surgery. Although prone
      esophagectomy is demonstrated as being both feasible and safe, there is no
      convincing evidence that it is superior to other forms of esophageal surgery.
      Most authors comment that the prone position is associated with superior surgical
      ergonomics and theoretically offers a number of physiological benefits.
      CONCLUSION: The ideal approach within minimally invasive esophageal surgery
      continues to be a subject of debate since no single method has produced
      outstanding results. Further clinical studies are required to see whether
      ergonomic advantages of the prone position can be translated into improved
      patient outcomes.

PMID- 22395954
TI  - The use of biodegradable (SX-ELLA) oesophageal stents to treat dysphagia due to
      benign and malignant oesophageal disease.
AB  - BACKGROUND: Biodegradable (BD) oesophageal stents have been available
      commercially only since 2008 and previous published research is limited. Our aim
      was to review the use of BD stents to treat dysphagia in benign or malignant
      oesophageal strictures. METHODS: Patients were identified from a prospective
      interventional radiological database. BD stents were inserted radiologically
      under fluoroscopic control. RESULTS: Between July 2008 and February 2011, 25
      attempts at placing SX-ELLA biodegradable oesophageal stents were made in 17
      males and five females, with a median age of 69 (range = 54-80) years. Two
      patients required more than one BD stent. Indications were benign strictures (n =
      7) and oesophageal cancer (n = 17). One attempt was unsuccessful for a technical
      success rate of 96% with no immediate complications. Clinical success rate was
      76%. Median dysphagia score before stent insertion was 3 (range = 2-4) compared
      to 2 (range = 0-3) after stent insertion (p = 0.0001). CONCLUSION: BD stents
      provide good dysphagia relief for the life time of the stent. They may help avoid
      the use of feeding tubes in patients having radical chemoradiotherapy or awaiting
      oesophagectomy. They do not require removal or interfere with radiotherapy
      planning via imaging. However, the reintervention rate is high after the stent
      dissolves.

PMID- 22395955
TI  - Flaxseed oil as a neuroprotective agent on lead acetate-induced monoamineric
      alterations and neurotoxicity in rats.
AB  - Lead remains a considerable occupational and public health problem, which is
      known to cause a number of adverse effects in both man and animals. Here, the
      neuroprotective effect of flaxseed oil (1,000 mg/kg) on lead acetate (20 mg/kg)
      induced alternation in monoamines and brain oxidative stress was examined in
      rats. The levels of lead, dopamine (DA), norepinephrine (NE), serotonin (5-HT),
      lipid peroxidation, nitrite/nitrate (NO), and glutathione (GSH) were determined;
      also, the activity of acetylcholinesterase (AChE) and Na(+)-K(+)-ATPase were
      estimated on different brain regions of adult male albino rats. The level of lead
      was markedly elevated in different brain regions of rats. This leads to
      enhancement of lipid peroxidation and NO production in brain with concomitant
      reduction in AChE activity and GSH level. In addition, the levels of DA, NE, and
      5-HT were decreased in the brain. These findings were associated with BAX over
      expression. Treatment of rats with flaxseed oil induced a marked improvement in
      most of the studied parameters as well as the immunohistochemistry features.
      These data indicated that dietary flaxseed oil provide protection against lead
      induced oxidative stress and neurotoxic effects.

PMID- 22395956
TI  - A one health framework for estimating the economic costs of zoonotic diseases on
      society.
AB  - This article presents an integrated epidemiological and economic framework for
      assessing zoonoses using a "one health" concept. The framework allows for an
      understanding of the cross-sector economic impact of zoonoses using modified risk
      analysis and detailing a range of analytical tools. The goal of the framework is
      to link the analysis outputs of animal and human disease transmission models,
      economic impact models and evaluation of risk management options to gain improved
      understanding of factors affecting the adoption of risk management strategies so
      that investment planning includes the most promising interventions (or sets of
      interventions) in an integrated fashion. A more complete understanding of the
      costs of the disease and the costs and benefits of control measures would promote
      broader implementation of the most efficient and effective control measures,
      contributing to improved animal and human health, better livelihood outcomes for
      the poor and macroeconomic growth.

PMID- 22395957
TI  - Poison-based commensal rodent control strategies in urban ecosystems: some
      evidence against sewer-baiting.
AB  - Sewers are historically considered the main reservoir for commensal rodents,
      posing threats to urban ecosystem health. Aboveground rodent signs are often
      assumed to give clues to high sewer infestation, which can chronically restock
      surface areas. Thus, current sewer-baiting programmes are mostly reactive,
      responding to increased surface infestation. Conversely, proactive sewer-baiting
      (regardless of infestation levels) is often disregarded because cost
      effectiveness is not always addressed. We explored the extent to which the
      surface infestation is related to rodent feeding activity on sewer and surface
      baits by analysing a set of proactive bait records in Bologna city, Italy. Sewer
      bait intakes were significantly lower than surface ones, suggesting that
      proactive sewer-baiting is generally less effective. As surface infestation
      increased, probability of recording surface bait intake increased significantly
      but this was not reflected by increased sewer bait intake, suggesting that
      surface infestation is not always a reliable indicator of sewer infestation. This
      should discourage the use of reactive sewer-baiting as a routine strategy. Poison
      based control programmes by themselves are scarcely predictable and strategically
      limited, and ideally they should be handled within an ecologically based
      integrated pest management approach for achieving satisfactory results.

PMID- 22395960
TI  - Prevention of biliary stent occlusion.

PMID- 22395958
TI  - Failure to detect simian immunodeficiency virus infection in a large Cameroonian
      cohort with high non-human primate exposure.
AB  - Hunting and butchering of wildlife in Central Africa are known risk factors for a
      variety of human diseases, including HIV/AIDS. Due to the high incidence of human
      exposure to body fluids of non-human primates, the significant prevalence of
      simian immunodeficiency virus (SIV) in non-human primates, and hunting/butchering
      associated cross-species transmission of other retroviruses in Central Africa, it
      is possible that SIV is actively transmitted to humans from primate species other
      than mangabeys, chimpanzees, and/or gorillas. We evaluated SIV transmission to
      humans by screening 2,436 individuals that hunt and butcher non-human primates, a
      population in which simian foamy virus and simian T-lymphotropic virus were
      previously detected. We identified 23 individuals with high seroreactivity to
      SIV. Nucleic acid sequences of SIV genes could not be detected, suggesting that
      SIV infection in humans could occur at a lower frequency than infections with
      other retroviruses, including simian foamy virus and simian T-lymphotropic virus.
      Additional studies on human populations at risk for non-human primate zoonosis
      are necessary to determine whether these results are due to viral/host
      characteristics or are indicative of low SIV prevalence in primate species
      consumed as bushmeat as compared to other retroviruses in Cameroon.

PMID- 22395961
TI  - Acute fulminant hepatic failure associated with parvovirus B19 infection in an
      immunocompetent adult.

PMID- 22395962
TI  - Analysis of the barley bract suppression gene Trd1.
AB  - A typical barley (Hordeum vulgare) floret consists of reproductive organs three
      stamens and a pistil, and non-reproductive organs-lodicules and two floral
      bracts, abaxial called 'lemma' and adaxial 'palea'. The floret is subtended by
      two additional bracts called outer or empty glumes. Together these organs form
      the basic structural unit of the grass inflorescence, a spikelet. There are
      commonly three spikelets at each rachis (floral stem of the barley spike) node,
      one central and two lateral spikelets. Rare naturally occurring or induced
      phenotypic variants that contain a third bract subtending the central spikelets
      have been described in barley. The gene responsible for this phenotype was called
      the THIRD OUTER GLUME1 (Trd1). The Trd1 mutants fail to suppress bract growth and
      as a result produce leaf-like structures that subtend each rachis node in the
      basal portion of the spike. Also, floral development at the collar is not always
      suppressed. In rice and maize, recessive mutations in NECK LEAF1 (Nl1) and TASSEL
      SHEATH1 (Tsh1) genes, respectively, have been shown to be responsible for
      orthologous phenotypes. Fine mapping of the trd1 phenotype in an F(3) recombinant
      population enabled us to position Trd1 on the long arm of chromosome 1H to a 10
      cM region. We anchored this to a conserved syntenic region on rice chromosome
      Os05 and selected a set of candidate genes for validation by resequencing PCR
      amplicons from a series of independent mutant alleles. This analysis revealed
      that a GATA transcription factor, recently proposed to be Trd1, contained
      mutations in 10 out of 14 independent trd1 mutant alleles that would generate non
      functional TRD1 proteins. Together with genetic linkage data, we confirm the
      identity of Trd1 as the GATA transcription factor ortholog of rice Nl1 and maize
      Tsh1 genes.

PMID- 22395964
TI  - DNA origami: synthesis and self-assembly.
AB  - DNA origami is an emerging technology for designing defined two- and three
      dimensional (2D and 3D) DNA nanostructures. Here, we report an introductory
      practical guide with step-by-step experimental details for the design and
      synthesis of origami structures, and their size expansion in 1D and 2D space by
      means of self-assembly.

PMID- 22395963
TI  - Effects of resistance training on respiratory function in patients with chronic
      obstructive pulmonary disease: a systematic review and meta-analysis.
AB  - PURPOSE: Over the last decade, the potential use of resistance training (RT) for
      patients with chronic obstructive pulmonary disease (COPD) has gained increasing
      attention. Many COPD patients experience muscle dysfunction and reduced muscle
      mass, primarily as a result of chronic immobilization. These symptoms have been
      associated with reduced exercise tolerance and complaints of fatigue and dyspnea
      (even after minimal exertion). This paper presents findings from a systematic
      review that sought to: (1) present a meta-analysis of randomized controlled
      trials (RCT) investigating the effects of RT on respiratory function measures in
      patients with COPD and (2) investigate the existence of a dose-response
      relationship between intensity, duration and frequency of RT and assessed
      outcomes. METHODS: A systematic literature search of MEDLINE electronic database
      (January 1980 to December 2009) produced a body of research on the effects of RT
      with a control group in patients with COPD. Data analysis involved a random
      effects meta-analysis, in order to determine weighted mean differences with 95
      confidence intervals (95% CI) for each endpoint. All data were analyzed with the
      software package Review Manager V 4.2.10 (of the Cochrane Collaboration); 14 RCTs
      were included in the meta-analysis. RESULTS: Findings demonstrated that RT did
      not substantially increase forced expiratory volume in 1 s. In addition, the
      weighted mean difference was 2.71% of predicted (95% CI, -1.86 to 7.27; p = 0.25)
      or by absolute 0.08 L (95% CI, -0.03 to 0.19; p = 0.14). It appeared that maximum
      minute ventilation increased by 3.77 L/min (95% CI, -0.51 to 8.04; p = 0.08).
      CONCLUSIONS: Based on findings from the meta-analysis, RT produces a clinically
      and statistically significant effect on respiratory function (such as forced
      vital capacity) and is therefore recommended in the management of COPD.

PMID- 22395965
TI  - One-flask synthesis of cyclic diguanosine monophosphate (c-di-GMP).
AB  - The bacterial signaling molecule, cyclic diguanosine monophosphate (c-di-GMP),
      plays a key role in controlling biofilm formation and pathogenic virulence, among
      many other functions. It has widespread consequences for human health, and
      current research is actively exploring its molecular mechanisms. The convenient
      one-flask, gram-scale synthesis of c-di-GMP described here will facilitate these
      efforts.

PMID- 22395966
TI  - Synthesis of dumbbell-shaped cyclic RNAs for RNA interference.
AB  - RNA interference (RNAi) is a potent and highly specific gene-silencing phenomenon
      that was first reported for the nematode Caenorhabditis elegans. It has been
      discovered that genes could be silenced by introducing double-stranded RNAs
      (dsRNAs) complementary to the messenger RNA sequences. Since then, RNAi has been
      shown as an evolutionarily well-conserved process that plays an important role in
      host defense and in regulation of gene expression. Much effort has been dedicated
      to the application of the short dsRNA species (short interfering RNAs; siRNAs) as
      therapeutic agents, as they were shown to be effective in mammalian cells.
      Recently, we altered the structure of a siRNA molecule and produced dumbbell
      shaped nanocircular RNAs. RNA dumbbells were shown to be stabilized in serum
      compared with its siRNA counterpart, despite their natural RNA strand. It has
      also been found that RNA dumbbells containing a 23-bp stem and two 9-nt loops
      exhibit a prolonged RNAi effect in cultured mammalian cells. In this unit, we
      describe the synthesis of RNA dumbbells from the design, its enzymatic synthesis,
      and to the purification.

PMID- 22395967
TI  - Synthesis and application of highly reactive amino linkers for functional
      oligonucleotides.
AB  - Oligonucleotides are functionalized by conjugation with a variety of molecules,
      and aliphatic amino linkers have been frequently used as a tether for their
      modifications. This unit describes the syntheses and applications of novel amino
      linkers having a carbamate structure. Two major chemical properties of the
      primary amine are induced by the neighboring effect of the carbamate group, which
      are found to be optimum in an aminoethyl carbamate structure. First, the
      hydrophobic monomethoxytrityl group can be rapidly removed from the aminoethyl
      carbamate under very mild acidic conditions, while the deprotection is not
      completed in standard aliphatic amines even under high acid concentration. This
      significant feature enables the convenient purification of amino-modified
      oligonucleotides by using the hydrophobic interaction of the monomethoxytrityl
      group with a reverse-phase resin. Second, the introduction of the carbamate
      linkage reduces the pK(a) value of the neighboring primary amine, resulting in an
      increase in the conjugation yields with various functional molecules, such as
      those having active esters. The novel amino linkers that have an aminoethyl
      carbamate linkage indicate potent activity and are applicable for the preparation
      of various functional oligonucleotides.

PMID- 22395968
TI  - Oligodeoxynucleotide containing s-functionalized 2'-deoxy-6-thioguanosine: facile
      tools for base-selective and site-specific internal modification of RNA.
AB  - Chemically modified oligonucleotides play a significant role for genomic
      research. Modified nucleosides, such as with a fluorescent dye, can be obtained
      by chemical synthesis. Site-specifically modified long nucleic acids are obtained
      by ligation of chemically modified short oligonucleotides with enzyme,
      photochemistry, or catalytic DNA. The functionality-transfer ODN (FT-ODN), which
      contains 2'-deoxy-6-thioguanosine (6-thio-dG) functionalized with the 2
      methyliden-1,3-diketone group, is hybridized with the target RNA to trigger the
      selective functionalization of the 4-amino group of the cytosine base at pH 7 or
      the 2-amino group of the guanine base at pH 9.4 or at pH 7.4 in the presence of
      NiCl(2). In particular, the functionality-transfer reaction (FTR) under the
      alkaline conditions or neutral conditions in the presence of NiCl(2) proceeds
      rapidly and selectively to lead to the modification of the target guanine. The
      transfer reaction of the acetylene-containing diketone group produces the
      acetylene-modified RNA, which can be subjected to the Cu(I)-catalyzed "click
      chemistry" with a variety of azide compounds for highly specific, internal
      modification of RNA.

PMID- 22395969
TI  - Big pharma: a story of success in a market economy.
AB  - In this paper, I will argue that the current discussions about regulating certain
      activities concerning the pharmaceutical industry do miss a crucial point. The
      Pharmaceutical Industry is a story of success, providing a wealth of new
      discoveries and applied technologies, which have greatly enhanced our lives. The
      current call for strict regulation of the Pharmaceutical Industry makes the
      unwarranted assumption that such regulation will not disturb the mechanisms of
      the Industry's success. I will claim that a centralised regulation profoundly
      transforms the direction of travel. I will also claim that the role of the
      executive in bypassing regulations creates a parallel industry of subsidiary
      regulations to counter such bypassing. The predictable consequence is the
      increasing role of central regulatory control and the progressive slowing down of
      the success of the Pharmaceutical Industry leading towards an undesirable
      mediocrity. The conclusion I wish to advance is that our choices are not limited
      to 'a wild open market' and 'a regulated open market' scenarios, and the strategy
      to avoid a robustly regulated but mediocre Pharmaceutical Industry may involve
      'non-open market scenarios' which have so far been absent from the alternatives
      discussed.

PMID- 22395970
TI  - Dis-appearance and dys-appearance anew: living with excess skin and intestinal
      changes following weight loss surgery.
AB  - The aim of this article is to explore bodily changes following weight loss
      surgery. Our empirical material is based on individual interviews with 22
      Norwegian women. To further analyze their experiences, we build primarily on the
      phenomenologist Drew Leder's distinction between bodily dis-appearance and dys
      appearance. Additionally, our analysis is inspired by Simone de Beauvoir, Merleau
      Ponty and Julia Kristeva. Although these scholars have not directed their
      attention to obesity operations, they occupy a prime framework for shedding light
      on different dimensions of bodily change. In doing so, we were able to identify
      two main themes: The felt "inner" body versus the visible "surface" body and the
      "old" body versus the "new" body. In different, though interconnected ways, these
      main themes encompass tensions between changes the women experienced as
      contributing to a more "normal" and active life, feeling more accepted, and
      changes that generated ambivalence. In particular, their skin became increasingly
      problematic because it did not "shrink" like the rest of the body. On the
      contrary, it became looser and looser. Moreover, badsmelling folds of skin that
      wobbled, sweated and chafed at the smallest movement, aprons of fat hanging in
      front of their stomachs, batwing arms, thick flabby thighs and sagging breasts
      were described as a huge contrast to the positive response they received to their
      changed body shape when they were out and about with their clothes on. At the
      same time, they expressed ambivalence with regards to removing the excess skin by
      means of plastic surgery. Through their own and other women's experiences they
      learned removing the excess skin by means of surgery could be a double-edged
      sword. By illuminating the experiences of the ones undergoing such changes our
      article offers new insight in a scholarly debate predominated by medical research
      documenting the positive outcomes of weight loss surgery.

PMID- 22395971
TI  - Gold nanoparticles developed in sol-gel derived apatite--bioactive glass
      composites.
AB  - The study is focussed on synthesis and characterisation of a new sol-gel derived
      composite system consisting of nanocrystalline apatite, bioactive glass and gold
      nanoparticles, which are of interest both for regenerative medicine and for
      specific medical applications of the releasable gold nanoparticles. Samples dried
      at 110 degrees C and then heat treated for 30 min at 300 and 500 degrees C were
      investigated by thermal analysis (DTA/TG), X-ray diffraction (XRD), UV-VIS-NIR,
      Fourier Transform Infrared (FTIR) spectroscopy, X-ray Photoelectron(XPS)
      spectroscopy, Scanning Electron Microscopy (SEM) and Transmission Electron
      Microscopy (TEM). Gold nanoparticles and nanocrystalline apatite are developed
      already after heat treatment at 300 degrees C. XPS analysis clearly revealed the
      presence of both metallic and ionic gold species. The development of gold
      nanoparticles was evidenced by UV-VIS-NIR and TEM analysis, and their size
      increased from few nanometers to 25 nm by increasing the treatment temperature
      from 300 to 500 degrees C. The bioactivity of the samples immersed in simulated
      body fluid was demonstrated by XRD and SEM results.

PMID- 22395972
TI  - Isolation and characterization of 3-nitrophenol-degrading bacteria associated
      with rhizosphere of Spirodela polyrrhiza.
AB  - INTRODUCTION: The accelerated biodegradation of 3-nitrophenol (3-NP) in the
      rhizosphere of giant duckweed (Spirodela polyrrhiza) was investigated. MATERIALS
      AND METHODS: Biodegradation of 3-nitrophenol in the rhizosphere of a floating
      aquatic plant, S. polyrrhiza, was investigated by using three river water samples
      supplemented with 10 mg l(-1) of 3-NP. Isolation and enrichment culture of 3-NP
      degrading bacteria were performed in basal salts medium containing 3-NP (50 mg l(
      1)). The isolated strains were physiologically and phylogenetically characterized
      by using an API20NE kit and 16S rRNA gene sequencing. RESULTS AND DISCUSSION:
      Accelerated removal of 3-NP (100%) was observed in river water samples with S.
      polyrrhiza compared with their removal in plant-free river water. Also, 3-NP
      persisted in an autoclaved solution with aseptic plants, suggesting that the
      accelerated 3-NP removal resulted largely from degradation by bacteria inhabiting
      the plant rather than from adsorption and uptake by the plant. We successfully
      isolated six and four strains of 3-NP-degrading bacteria from the roots of S.
      polyrrhiza and plant-free river water, respectively. Phylogenetic analysis based
      on 16S rRNA gene divided the 3-NP-degrading bacteria into two taxonomic groups:
      the genera Pseudomonas and Cupriavidus. The strains belonging to the genus
      Cupriavidus were only isolated from the roots of duckweed. All strains isolated
      from the roots utilized 3-NP (0.5 mM) as a sole carbon and energy source,
      indicating that they could have contributed to the accelerated degradation of 3
      NP in the rhizosphere of S. polyrrhiza. CONCLUSIONS: The rhizoremediation using
      S. polyrrhiza and its rhizosphere bacteria can be an effective strategy for
      cleaning up the 3-NP-contaminated surface waters.

PMID- 22395973
TI  - Integration of global spectral karyotyping, CGH arrays, and expression arrays
      reveals important genes in the pathogenesis of glioblastoma multiforme.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary tumor of the
      central nervous system in adults. Patients with GBM have few treatment options,
      and their disease is invariably fatal. Molecularly targeted agents offer the
      potential to improve patient treatment; however, the use of these will require a
      fuller understanding of the genetic changes in this complex tumor. METHODS: We
      analyzed a series of 32 patients with GBM with array comparative genomic
      hybridization in combination with gene expression analysis. We focused on the
      recurrent breakpoints found by spectral karyotyping (SKY). RESULTS: By SKY we
      identified 23 recurrent breakpoints of the 202 translocations found in GBM cases.
      Gains and losses were identified in chromosomal regions close to the breakpoints
      by array comparative genomic hybridization. We evaluated the genes located in the
      regions involved in the breakpoints in depth. A list of 406 genes that showed a
      level of expression significantly different between patients and control subjects
      was selected to determine their effect on survival. Genes CACNA2D3, PPP2R2B, SIK,
      MAST3, PROM1, and PPP6C were significantly associated with shorter survival
      (median 200 days vs. 450 days, P<=0.03). CONCLUSIONS: We present a list of genes
      located in regions of breakpoints that could be grounds for future studies to
      determine whether they are crucial in the pathogenesis of this type of tumor, and
      we provide a list of six genes associated with the clinical outcome of patients
      with GBM.

PMID- 22395974
TI  - Comparison of the 6th and 7th Editions of the UICC-AJCC TNM Classification for
      Esophageal Cancer.
AB  - BACKGROUND: The new 7th edition of the Union for International Cancer Control
      American Joint Committee on Cancer (UICC-AJCC) tumor, node, metastasis (TNM)
      staging system is the ratification of data-driven recommendations from the
      Worldwide Esophageal Cancer Collaboration database. Generalizability remains
      questionable for single institutions. The present study serves as a validation of
      the 7th edition of the TNM system in a prospective cohort of patients with
      predominantly adenocarcinomas from a single institution. METHODS: Included were
      patients who underwent transhiatal esophagectomy with curative intent between
      1991 and 2008 for invasive carcinoma of the esophagus or gastroesophageal
      junction. Excluded were patients who had received neoadjuvant
      chemo(radio)therapy, patients after a noncurative resection and patients who died
      in the hospital. Tumors were staged according to both the 6th and the 7th
      editions of the UICC-AJCC staging systems. Survival was calculated by the Kaplan
      Meier method, and multivariate analysis was performed with a Cox regression
      model. The likelihood ratio chi-square test related to the Cox regression model
      and the Akaike information criterion were used for measuring goodness of fit.
      RESULTS: A study population of 358 patients was identified. All patients
      underwent transhiatal esophagectomy for adenocarcinoma. Overall 5-year survival
      rate was 38%. Univariate analysis revealed that pT stage, pN stage, and pM stage
      significantly predicted overall survival. Prediction was best for the 7th
      edition, stratifying for all substages. CONCLUSIONS: The application of the 7th
      UICC-AJCC staging system results in a better prognostic stratification of overall
      survival compared to the 6th edition. The fact that the 7th edition performs
      better predominantly in patients with adenocarcinomas who underwent a transhiatal
      surgical approach, in addition to findings from earlier research in other
      cohorts, supports its generalizability for different esophageal cancer practices.

PMID- 22395975
TI  - Vascular endothelial growth factor receptor 2 gene polymorphisms as predictors
      for tumor recurrence and overall survival in non-small-cell lung cancer.
AB  - PURPOSE: VEGFR-2 gene displays several functional germline polymorphisms with
      impact on VEGFR-2 mediated angiogenesis. Our purpose was to evaluate VEGFR-2
      polymorphisms as prognostic markers for tumor recurrence and overall survival
      (OS) in non-small-cell lung cancer (NSCLC). METHODS: In total, 209 Caucasian
      patients who had been surgically treated for NSCLC between 1996 and 2010 were
      included in this study. Genotyping of peripheral blood cells was performed by
      TaqMan(r) genotyping assays or polymerase chain reaction for five VEGFR-2
      polymorphisms. Chi- square test, Kaplan-Meier estimator, and Cox regression
      hazard model were used to assess the prognostic value of VEGFR-2 polymorphisms.
      RESULTS: VEGFR-2+4422 (AC)10-14 polymorphism was identified as a positive
      prognostic marker for time to metastasis (11/12 vs. 11/11 (AC) repeats: hazard
      ratio (HR), 0.28; 95% confidence interval (CI), 0.11-0.75; p=0.012) and OS (11/12
      vs. 11/11 (AC) repeats: HR, 0.41; 95% CI, 0.21-0.82; p=0.012) in squamous cell
      carcinoma. For adenocarcinoma, VEGFR-2-906 C>T (C/T vs. CC: HR, 0.19; 95% CI,
      0.43-0.82; p=0.027) and VEGFR-2-271 G>A (G/A vs. G/G: HR, 0.25; 95% CI, 0.07
      0.86; p=0.027) predicted longer time to local recurrence and VEGFR-2-906 C>T was
      a predictor for better OS (T/T vs. C/C: HR, 0.28; 95% CI, 0.09-0.84; p=0.024).
      CONCLUSIONS: VEGFR2 germline polymorphisms predict tumor recurrence and OS in
      NSCLC.

PMID- 22395977
TI  - Tobacco use is associated with increased recurrence and death from gastric
      cancer.
AB  - BACKGROUND: Tobacco use increases the risk of developing gastric cancer. We
      examined the hypothesis that gastric cancer developing in patients with a history
      of tobacco use may be associated with increased risk of cancer-specific death
      after curative surgical resection. METHODS: From the Memorial Sloan-Kettering
      Cancer Center Gastric Cancer prospective surgical database, we collected baseline
      demographic data and tumor characteristics from all patients who had undergone
      curative resection for gastric cancer between 1995 and 2009 and who had not
      received pre- or postoperative chemo- or radiotherapy. A smoking history was
      defined as >100 cigarettes' lifetime use. The primary end point was gastric
      cancer disease-specific survival (DSS); secondary end points were 5-year disease
      free survival (DFS) and overall survival (OS). Gastric cancer-specific hazard was
      modeled by Cox regression. RESULTS: A total of 699 eligible patients were
      identified with a median age of 70 years (range 25-96 years); 410 (59%) were
      current or previous smokers. Smoking was associated with gastroesophageal
      junction/cardia tumors and white non-Hispanic ethnicity. Multivariate analysis
      included the following variables: tumor stage, age, performance status, diabetes
      mellitus, gender, and tumor location. In this analysis, the hazard ratio for
      gastric cancer DSS in smokers was 1.43 (95% confidence interval 1.08-1.91,
      P=0.01). Smoking was also an independent significant risk factor for worse 5-year
      DFS (hazard ratio 1.46, P=0.007) and OS (hazard ratio 1.48, P=0.003). Among 516
      patients for whom tobacco pack-year usage was available, both heavy (>=20 pack
      years) and light (<20 pack-years) tobacco use was significantly associated with
      DSS, DFS, and OS. CONCLUSIONS: Smoking history appears to be an independent risk
      factor for death from gastric cancer in patients who have undergone curative
      surgical resection.

PMID- 22395978
TI  - Predicting pathological response to neoadjuvant chemoradiotherapy in locally
      advanced rectal cancer using 18FDG-PET/CT.
AB  - BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemoradiation
      (CRT) has been observed in 15-30% of patients with locally advanced rectal cancer
      (LARC). The objective of this study was to determine whether PET/CT can predict
      pCR and disease-free survival in patients receiving CRT with LARC. METHODS: This
      is a retrospective review of patients with EUS-staged T3-T4, N+rectal tumors
      treated with CRT, who underwent pre/post-treatment PET/CT from 2002-2009. All
      patients were treated with CRT and surgical resection. Standardized uptake value
      (SUV) of each tumor was recorded. Logistic regression was used to analyze the
      association of pre-CRT SUV, post-CRT SUV, %SUV change, and time between CRT and
      surgery, compared with pCR. Kaplan-Meier estimation evaluated significant
      predictors of survival. RESULTS: Seventy patients (age 62 years; 42M:28F) with
      preoperative stage T3 (n=61) and T4 (n=9) underwent pre- and post-CRT PET/CT
      followed by surgery. The pCR rate was 26%. Median pre-CRT SUV was 10.8, whereas
      the median post-CRT SUV was 4 (P=0.001). Patients with pCR had a lower median
      post-CRT SUV compared with those without (2.7 vs. 4.5, P=0.01). Median SUV
      decrease was 63% (7.5-95.5%) and predicted pCR (P=0.002). Patients with a pCR had
      a greater time interval between CRT and surgery (median, 58 vs. 50 days) than
      those without (P=0.02). Patients with post-CRT SUV<4 had a lower recurrence
      compared with those without (P=0.03). Patients with SUV decrease>=63% had
      improved overall survival at median follow-up of 40 months than those without
      (P=0.006). CONCLUSIONS: PET/CT can predict response to CRT in patients with LARC.
      Posttreatment SUV, %SUV decrease, and greater time from CRT to surgery correlate
      with pCR. Post-CRT, SUV<4, and SUV decrease>=63% were predictive of recurrence
      free and overall survival.

PMID- 22395979
TI  - The role of adjuvant chemotherapy for localized squamous cell esophageal cancer:
      current Japanese standard and the unending role of the drawing board.

PMID- 22395981
TI  - Managing the breast in patients who test positive for hereditary breast cancer.
AB  - PURPOSE AND METHODS: The patient who tests positive for hereditary breast cancer
      has several important decisions to make regarding management of the breasts.
      Before making an informed decision, the physician must first review the screening
      assessment to make sure that the patient does not harbor an undiagnosed breast
      malignancy. In the absence of a malignancy, the management options for the breast
      range from nonoperative surveillance to prophylactic mastectomy to prevent
      cancer. In the event that a breast malignancy is diagnosed after a positive
      genetic test, implications for management of both the affected and the unaffected
      breast must be considered. RESULTS AND DISCUSSION: The clinical assessment of the
      patient who tests positive is discussed. If routine pretest mammograms were
      negative, should additional diagnostic studies be performed to exclude an
      undetected/occult malignancy, and if so, what are the roles of magnetic resonance
      imaging, ultrasonography, digital mammogram, and detection of breast cancer
      circulating tumor cells? Medical management may include increased surveillance
      and chemopreventative therapy, including tamoxifen and oral contraceptives.
      Surgical interventions may be undertaken to reduce risk in people with a genetic
      susceptibility gene for breast or ovarian cancer; risk-reducing surgical options
      include mastectomy with or without reconstruction and nipple-sparing techniques.
      Finally, we discuss management decisions for women who test positive and who are
      diagnosed with a primary breast cancer, compared to women who have no obvious
      primary tumor but test positive.

PMID- 22395980
TI  - Prediction of response and prognosis by a score including only pretherapeutic
      parameters in 410 neoadjuvant treated gastric cancer patients.
AB  - BACKGROUND: Response to neoadjuvant chemotherapy is an independent prognostic
      factor in locally advanced gastric cancer. However, no prospectively tested
      pretherapeutic parameters predicting response and/or survival in gastric cancer
      are available in clinical routine. METHODS: We evaluated the prognostic
      significance of various clinical pathologic parameters in 410 patients who were
      treated with neoadjuvant chemotherapy followed by gastrectomy. Clinical and
      histopathologic response evaluation was performed by using standardized criteria.
      A prognostic score was created on the basis of the variables identified in the
      multivariate analysis. RESULTS: Three pretherapeutic parameters were identified
      as positive predictive factors for response and prognosis: tumor localization in
      the middle third of the stomach (P=0.001), well-differentiated tumors (P=0.001),
      and intestinal tumor type according to Lauren classification (P=0.03). A
      prognostic index was constructed, dividing the patients into three risk groups:
      low (n=73), intermediate (n=274), and high (n=63). The three groups had
      significantly different clinical (P=0.007) and histopathologic response rates
      (P=0.001) and survival times, with a median survival time that was not reached in
      the low-risk group, 39.2 months in the intermediate-risk group, and 20.5 months
      in the high-risk group. The corresponding 5-year survival rates were 65.3, 41.2,
      and 21.2% (P<0.001), respectively. CONCLUSIONS: A simple scoring system based on
      three clinicopathologic parameters accurately predicts response and prognosis in
      neoadjuvant treated gastric cancer. This system provides additional useful
      information that could be applied to select gastric cancer patients
      pretherapeutically for different treatment approaches. Prospective testing of the
      score in an independent patient cohort is warranted.

PMID- 22395982
TI  - Alternatives for optimizing outcomes in oncoplastic breast surgery.
AB  - BACKGROUND: Breast conservation treatment (BCT) is an accepted option for the
      treatment of breast malignancies. However, as suboptimal surgical techniques
      result in poor cosmetic outcomes, a plethora of operative approaches to prevent
      potential deformity has emerged in contemporary literature. Many of these
      procedures, referred to as oncoplastic breast surgery (OBS), depend on complex
      mammoplasty-type procedures, often with contralateral symmetrisation, and the
      frequent use of volume replacement techniques with implants or autologous tissue
      flaps. However, there have been reports of moderately high rates of complications
      for these types of procedures. OBJECTIVE: To propose surgical approaches that
      reduce tissue manipulation and lower complication rates without sacrificing local
      control and survival. METHODS: A description of methods is presented, involving
      closely coordinated collaboration with members of the interdisciplinary team to
      enable accurate resection with minimal tissue loss for appropriate margins,
      allowing adequate retained tissue for acceptable cosmesis. RESULTS: Using these
      techniques, more women with breast malignancies may undergo BCT without elaborate
      mammoplasty procedures or volume replacement operations with implants or
      autologous flaps. CONCLUSIONS: The approaches described are alternatives to the
      conventional volume displacement techniques for optimising outcomes with OBS.
      They allow a greater proportion of women to undergo BCT with less tissue
      manipulation and lower complication rates.

PMID- 22395983
TI  - The treatment of peritoneal carcinomatosis of colorectal cancer with complete
      cytoreductive surgery and hyperthermic intraperitoneal peroperative chemotherapy
      (HIPEC) with oxaliplatin: a Belgian multicentre prospective phase II clinical
      study.
AB  - BACKGROUND: Up to 25% of patients with metastatic colorectal cancer (CRC) present
      with peritoneal carcinomatosis (PC) as the only site of metastases. Complete
      cytoreductive surgery (CCRS) followed by hyperthermic intraperitoneal
      chemotherapy (HIPEC) aims for locoregional disease control and long-term
      survival. Oxaliplatin is effective for treating advanced CRC. This study assesses
      the safety and efficacy of CCRS with HIPEC with oxaliplatin for patients with PC
      of CRC. METHODS: A Belgian prospective multicenter registry was performed to
      monitor perioperative morbidity and assess mortality, disease-free survival
      (DFS), and overall survival (OS). RESULTS: Forty-eight consecutive patients
      underwent CCRS (R0/1) with HIPEC (male/female ratio 17/31, median age 60 years,
      range 24-76 years). Median PC index was 11 (range 1-22). Median operation time
      was 460 (range 125-840) min, with a median blood loss of 475 (range 2-6,000) ml.
      Thirty-day mortality was 0%. Complication rate (any grade) was 52.1%. Anastomotic
      leakage occurred in 10.4% of patients, bleeding in 6.3%, and bowel perforation in
      2.1%. Median hospital stay was 20 (range 5-65) days. At median follow-up of 22.7
      (range 3.2-55.7) months, OS was 97.9% [95% confidence interval (CI) 86.1-99.7] at
      1 year and 88.7% (95% CI 73.6-95.4) at 2 years. DFS at 1 year was 65.8% (95% CI
      52.3-76.2) and 45.5% (95% CI 34.3-55.9) at 2 years. Median time until recurrence
      was 19.8 months (95% CI 12-upper limit not defined). Only after dichotomizing PC
      index was a significant difference in OS found between low and high PC index.
      CONCLUSIONS: CCRS followed by HIPEC with oxaliplatin for PC from CRC can be
      implemented with acceptable morbidity. Long-term DFS and OS can be achieved in
      selected patients.

PMID- 22395984
TI  - Surgical complications in gastric cancer patients preoperatively treated with
      chemotherapy: their risk factors and clinical relevance.
AB  - BACKGROUND: This study was designed to identify risk factors and oncological
      value for the development of postoperative complications after gastrectomy in
      gastric cancer patients with preoperative chemotherapy. METHODS: A total of 123
      gastric cancer patients who underwent gastrectomy after chemotherapy were
      enrolled in this study. The incidence, type, risk factors, and prognostic value
      of surgical complications were evaluated. RESULTS: The postoperative complication
      rate was 29.3% and mortality rate was 1.6%. The development of postoperative
      complications was associated with operation time (>200 min) and transfusion
      during surgery. The resection extent, preoperative chemotherapy cycles and
      regimens, tumor stage, and patients' nutritional status were not predictive
      factors for the development of surgical complications. In the multivariate
      analysis, operation time was an independent risk factor for the development of
      postoperative complications (odds ratio, 3.813; P = 0.011). The median follow-up
      after surgery was 19 months. The 3-year, disease-free survival was 57.1% in
      patients without complications and 25.7% in patients with complications (P =
      0.004). Multivariable analysis demonstrated postoperative complications were a
      significant prognostic factor for disease-free survival (hazard ratio, 2.676; P =
      0.024). CONCLUSIONS: The incidence of surgical complications was high in gastric
      cancer patients who received preoperative chemotherapy. Long operation time was a
      risk factor for surgical complications, and the development of postoperative
      complication was predictive of patients' prognoses.

PMID- 22395985
TI  - Long-term outcomes of repeat hepatic resection in patients with recurrent
      hepatocellular carcinoma and analysis of recurrent types and their prognosis: a
      single-center experience in China.
AB  - BACKGROUND: Recurrent hepatocellular carcinoma (HCC) after curative resection
      usually originates from intrahepatic metastasis (IM) or multicentric occurrence
      (MO). The long-term outcomes of repeat hepatic resection in patients with
      different types of recurrence have not been evaluated in a large number of
      patients. The surgical indications for recurrent HCC remain controversial. The
      purpose of this study was to investigate long-term outcomes of repeat hepatic
      resection and clinicopathologic factors associated with different types of
      recurrent HCC, and to single out principle differentiating factors between IM and
      MO. METHODS: 82 patients who underwent repeat hepatic resection for recurrent HCC
      were retrospectively studied. The recurrent type was evaluated by histopathologic
      analysis of primary and recurrent HCC. The recurrence and survival rates as well
      as clinicopathologic factors associated with different types of recurrence were
      analyzed. RESULTS: 45 patients (54.9%) had confirmed with IM, and 37 patients
      (45.1%) had with MO. The recurrence rates in the MO patients after initial or
      repeat resection were significantly lower than those in the IM patients (p <
      0.001). The overall survival rates in the MO patients after initial or repeat
      resection were significantly higher than those in the IM patients (p < 0.001).
      Recurrence-free time was identified as the most significant differentiating
      factor between IM and MO. A recurrence-free time of 18 months after initial
      resection was a significant cutoff time point for differentiating between IM and
      MO. A recurrence-free time of less than or equal to 18 months and microvascular
      invasion at repeat resection were independent adverse prognostic factors for
      overall survival after repeat hepatic resection. CONCLUSIONS: Repeat hepatic
      resection resulted in much higher survival rates in the MO patients than in the
      IM patients. Repeat hepatic resection could be recommended for those patients in
      whom the recurrent HCC occurs more than 18 months after initial resection.

PMID- 22395986
TI  - Telomere-specific reverse transcriptase (hTERT) and cell-free RNA in plasma as
      predictors of pathologic tumor response in rectal cancer patients receiving
      neoadjuvant chemoradiotherapy.
AB  - PURPOSE: To investigate whether the plasma levels of cell-free RNA (cfRNA) and
      telomere-specific reverse transcriptase mRNA (hTERT) are associated with tumor
      response in rectal cancer patients who received preoperative chemoradiotherapy
      (pCRT). METHODS: Patients who underwent pCRT for rectal cancer and for whom
      baseline and paired post-pCRT blood samples were available were studied. On the
      basis of tumor regression score, patients were classified as having response or
      having no response. Clinical variables and plasma levels of cfRNA and hTERT
      before and after the pCRT were evaluated. The association between each predictor
      and tumor response was assessed by univariate and multivariate analyses. RESULTS:
      Of 98 eligible patients, 45 were determined to respond to therapy, and 53 did not
      respond to therapy. In univariate analysis, gender (P = 0.040), baseline levels
      of cfRNA (P = 0.026), post-pCRT levels of both hTERT and cfRNA (P < 0.0001 and P
      = 0.001, respectively), and the difference between the post- and pre-pCRT levels
      of both hTERT and cfRNA (P = 0.009 and P = 0.001, respectively) were found to be
      significant predictors of tumor response. In multivariate analysis, using
      variables that were available before pCRT, cfRNA levels and gender independently
      predicted the tumor response, while in multivariate analysis, which used all of
      the variables available before the surgical procedure, the post-pCRT levels of
      cfRNA and the difference between the post- and pre-pCRT levels of cfRNA
      independently predicted tumor response. CONCLUSIONS: Plasma levels of cfRNA and
      hTERT are promising markers of tumor response to pCRT for rectal cancer.

PMID- 22395987
TI  - What is a safe future liver remnant size in patients undergoing major hepatectomy
      for colorectal liver metastases and treated by intensive preoperative
      chemotherapy?
AB  - BACKGROUND: A multidisciplinary approach involving preoperative chemotherapy has
      become common practice in patients with colorectal liver metastases (CLM). The
      definition of a safe future liver remnant (FLR) volume based on preoperative
      clinical data in these patients is lacking. Our aim was to identify predictors of
      postoperative morbidities in patients undergoing major hepatectomy after
      intensive preoperative chemotherapy for CLM. METHODS: Between January 2000 and
      August 2010, a total of 101 consecutive patients with CLM underwent major
      hepatectomy after preoperative chemotherapy (>=6 cycles of oxaliplatin or
      irinotecan regimen with or without targeted therapies). The FLR ratio was
      calculated by two formulas: actual FLR (aFLR) ratio, and standardized FLR (sFLR)
      ratio. Predictors of postoperative overall morbidity, sepsis, and liver failure
      were identified by univariate and multivariate analyses. RESULTS: Fifty-eight
      patients (57.4%) had 95 postoperative complications. Sepsis and postoperative
      liver failure occurred in 23 (22.8%) and 16 patients (15.8%), respectively. On
      univariate analysis, small aFLR ratio was significantly associated with all
      complications, and sFLR ratio was associated with sepsis and liver failure. In
      receiver-operating characteristic analysis, the cutoff of aFLR ratio in
      predicting overall morbidity, sepsis, and liver failure was 44.8, 43.1, and
      37.7%, respectively, and that of sFLR ratio in predicting sepsis and liver
      failure was 43.6 and 48.5%, respectively. On multivariate analysis, these aFLR
      and sFLR ratio cutoffs were independent predictors of all complications and of
      sepsis and liver failure, respectively. CONCLUSIONS: This study provides a cutoff
      FLR ratio for safe postoperative outcome after major hepatectomy in CLM patients
      receiving six or more cycles of preoperative chemotherapy.

PMID- 22395988
TI  - Postoperative prognostic predictors of pancreatic ductal adenocarcinoma: clinical
      analysis and immunoprofile on tissue microarrays.
AB  - BACKGROUND: Most pancreatic ductal adenocarcinomas (PDACs) metastasize even after
      curative resection. Our goal was to investigate the important factors affecting
      metastasis and overall survival (OS). METHODS: We studied 88 PDACs with R0
      resection and evaluated immunohistochemical markers on tissue microarrays to
      assess the expression levels of the following: EGFR, amphiregulin, VEGF, p-c-met,
      MMP2, MMP7, MMP9, CXCR3, and CXCR4. RESULTS: The median OS in patients who had
      positive versus negative expression of AREG and MMP9 were 25 versus 16 months and
      24 versus 13 months, respectively (P = 0.03, P = 0.006). However, the median OS
      in patients with positive versus negative expression of MMP2 was 22 versus 37
      months (P = 0.04). Immunoprofiles also revealed that patients with positive
      expression of p-c-met or VEGF had significantly shorter distant metastasis-free
      survival. Adjuvant treatment, postoperative decrease of CA 19-9, angiolymphatic
      invasion, AREG, and MMP2 were independent prognostic factors affecting OS in
      multivariate analysis. CONCLUSIONS: Immunoprofiles revealed the groups with
      unfavorable tumor biology: negative expression of AREG and positive expression of
      MMP2. Also, high immunoreactivity of p-c-met or VEGF seemed to be associated with
      early distant organ metastasis in R0 resected PDACs; however, they still need to
      be further investigated. These results may give us useful insights in
      understanding the tumor biology and the patterns of PDAC dissemination.

PMID- 22395990
TI  - "It's not the destination, it's the journey": 2011 Society of Surgical Oncology
      presidential address.

PMID- 22395991
TI  - Thyroid cancer detection with dual-isotope parathyroid scintigraphy in primary
      hyperparathyroidism.
AB  - BACKGROUND: Thyroid cancer cells have been shown to take up (99m)Tc-sestamibi.
      The role for (99m)Tc-sestamibi scintigraphy (Tc-MIBI) in the diagnosis of thyroid
      cancer in patients with primary hyperparathyroidism (PHPT) is unclear. Our aim
      was to determine whether dual-isotope parathyroid scintigraphy is useful in
      identifying thyroid cancer. METHODS: A prospective database of 3,187 patients who
      underwent neck exploration for PHPT was reviewed to identify patients who had
      concurrent thyroid resection. Patients with benign and malignant thyroid disease
      were comparatively analyzed. RESULTS: A total of 470 patients underwent both
      thyroidectomy and parathyroidectomy (reoperations in 21%). Benign disease (n =
      391, 83%) was more common than malignancy [papillary thyroid cancer (n = 75) and
      medullary thyroid cancer (n = 5); 1 had both]. Dual-isotope scintigraphy obtained
      in 374 patients (80%) had a sensitivity of 67% and a positive predictive value of
      66% for parathyroid adenoma localization in these patients with thyroid disease.
      False-positive scintigraphy occurred in 22% with benign and 45% with malignant
      thyroid disease (P = 0.002). On Tc-MIBI imaging, 54 (86%) of 63 patients with
      malignancy had hot nodules, compared to 248 (81%) of 308 patients with benign
      disease (P = 0.49). On I-123 imaging, 34 (54%) of 63 patients with malignancy had
      cold nodules, compared to 42 (14%) of 304 patients with benign disease (P <
      0.001). A dual-isotype phenotype of both Tc-MIBI-Hot and I-123-Cold had
      sensitivity 52%, specificity 88%, positive predictive value 47%, and negative
      predictive value 90% for detecting a thyroid malignancy. CONCLUSIONS: A Tc-MIBI
      Hot/I-123-Cold phenotype is very specific for detecting thyroid malignancy.
      Patients with this imaging phenotype should strongly be considered for
      preoperative ultrasound-guided biopsy. Patients found intraoperatively to have
      false-positive parathyroid scintigraphy should be evaluated for thyroid cancer.

PMID- 22395992
TI  - Nodal counts on MDCT as a surrogate marker for surgical curability in gastric
      cancer.
AB  - BACKGROUND: Thin-slice multidetector row computed tomography (MDCT) has emerged
      as a promising diagnostic modality in various cancers. This study was designed to
      evaluate the utility of metastatic nodal counts on MDCT as a surrogate maker for
      surgical curability in gastric cancer. METHODS: Between 2005 and 2007, a total of
      92 patients with gastric cancer underwent preoperative MDCT at a slice thickness
      of 1.0 mm at our hospital. All regional lymph nodes showing metastatic
      involvement were preoperatively counted. RESULTS: Although the total counts of
      metastatic lymph nodes on MDCT were significantly smaller than those found by
      histopathology (P = 0.00001), there was a significant correlation between nodal
      counts on MDCT and histopathology by Spearman's analysis [P < 0.0001, pathologic
      counts = 1.63x (counts on MDCT) + 2.5]. Nodal counts on MDCT of >=4 were analyzed
      as putative pathologic nodal counts of >=8 by the equation, and pathologic
      metastatic nodal counts of >=8 were most significantly correlated with
      noncurative resection (P < 0.0001). According to the logistic regression
      analysis, nodal counts on MDCT of >=4 were a significant independent variable for
      noncurative resection (P = 0.0052, odds ratio 26.68). Nodal counts on MDCT of >=4
      could distinguish noncurative patients from curative patients with 94.4%
      sensitivity and 71.6% specificity. CONCLUSIONS: Nodal counts on MDCT could be a
      reliable surrogate maker for surgical curability of gastric cancer. This marker
      might enable us to select prospective candidates for additional or alternative
      treatments in gastric cancer.

PMID- 22395993
TI  - Adjuvant surgery in testicular cancer patients undergoing postchemotherapy
      retroperitoneal lymph node dissection.
AB  - PURPOSE: To evaluate the clinicopathologic characteristics of patients undergoing
      adjuvant surgery during postchemotherapy retroperitoneal lymph node dissection
      (PC-RPLND). METHODS: From 2004 to 2010, 85 testicular cancer patients underwent
      PC-RPLND by a single surgeon (S.D.). A bilateral template approach was utilized
      with nerve-sparing technique whenever feasible. The clinicopathologic and outcome
      of patients who underwent removal of any organ or structure during PC-RPLND were
      reviewed. RESULTS: Of 85 patients undergoing PC-RPLND, 28 (33%) required adjuvant
      procedures. Thirteen (15%) required vascular procedures including cavotomy/caval
      resection in 6, aortic resection in 8, common iliac vessels resection in 4, and
      renal vessels resection/reimplant in 2. Twelve patients (14%) required adjuvant
      nephrectomy (ten of 12 left-sided). There was one ureteral resection with
      appendiceal substitution, one partial duodenectomy, two cholecystectomy, two
      thoracotomies, four liver resection/biopsy, and one neck dissection. There were
      eight early complications (28%), including vocal cord paralysis, brachial plexus
      injury, lower extremities compartment syndrome, thigh numbness, upper
      gastrointestinal bleeding, retroperitoneal hematoma, and alcohol withdrawal. No
      perioperative death was reported. Retroperitoneal pathology revealed mature
      teratoma in 11 patients (39%), fibrosis in 8 (28%), and viable germ cell tumor
      (GCT) in 9 (32%). A total of 75, 82, and 66% of patients with fibrosis, teratoma,
      and viable GCT, respectively, had no evidence of recurrence at a mean follow-up
      of 18 months. CONCLUSIONS: Many patients undergoing PC-RPLND require adjuvant
      surgery, including vascular procedures and nephrectomy. The excellent outcomes
      associated with low operative morbidity and mortality validates such aggressive
      surgical approaches performed by experienced surgeons.

PMID- 22395994
TI  - Management of patients with primary hyperparathyroidism and concurrent thyroid
      disease: an evolving field.

PMID- 22395995
TI  - Outcome of patients with ductal carcinoma in situ and sentinel node biopsy.
AB  - BACKGROUND: In sentinel node biopsy (SNB), tumor-positive findings, mainly
      micrometastases and isolated tumor cells (ITC) have been found in up to 8%-16% of
      patients with pure ductal carcinoma in situ (DCIS) or microinvasive DCIS (DCISM).
      The prognostic significance of such findings is largely unknown. The aim of this
      study is to examine the outcome of DCIS and DCISM patients with SNB. METHODS: A
      total of 280 breast cancer patients with pure or microinvasive DCIS underwent SNB
      between April 2001 and December 2010 at the Breast Surgery Unit of Helsinki
      University Central Hospital. Patient, tumor, SNB procedure, and follow-up data
      were gathered. The median follow-up was 50 months (range 7-123 months). RESULTS:
      Altogether, 21 patients had tumor-positive sentinel node findings. Of these, 14
      were in pure DCIS patients (1 macrometastasis, 1 micrometastasis, 12 ITC) and 7
      in DCISM patients (1 macrometastasis, 2 micrometastases, 4 ITC). Also, 16
      patients, 10 with pure DCIS and 6 with DCISM, underwent completion axillary lymph
      node dissection (ALND). Only 1 of them, a patient with DCISM, had additional
      tumor positive finding in the ALND. During a median follow-up of 50 months (range
      7-123 months) there were 5 local recurrences. One patient with pure DCIS and
      tumor-negative SNB developed overt axillary metastases and later also distant
      metastases. CONCLUSIONS: DCIS and DCISM patients do have tumor positive findings,
      but a majority of these are ITC or micrometastases. In light of this study, these
      findings do not affect the outcome of DCIS or DCISM patients.

PMID- 22395996
TI  - Clinical and ultrasonographic findings affecting nondiagnostic results upon the
      second fine needle aspiration for thyroid nodules.
AB  - BACKGROUND: The purpose of this study was to investigate the clinical and
      ultrasonographic (US) findings affecting the nondiagnostic cytology and
      malignancy rate in thyroid nodules with nondiagnostic cytology upon a second
      ultrasound-guided fine needle aspiration (US-FNA). MATERIALS AND METHODS: A total
      of 1124 nodules in 1081 patients (M:F=111:970; mean age, 48.5 years) with 2 or
      more US-FNAs were included. Clinical and US features were compared between the
      nodules with nondiagnostic results and diagnostic results from their second FNA
      using univariate and multivariate analyses. The malignancy rate was analyzed in
      terms of nondiagnostic cytology. RESULTS: Among 458 nondiagnostic results of the
      initial FNA, 94 nodules (20.5%) still had nondiagnostic results on the second
      FNA. Having cystic portion>50% (odds ratio [OR]=2.845, P=.0001), nondiagnostic
      cytology of the first FNA (OR=2.813, P<.0001), a nodule size<=5 mm (OR=1.742,
      P=.0331), or hypoechogenicity (OR=1.512, P=.0404) were factors significantly
      affecting the incidence of nondiagnostic results in the second US-FNA based on
      multivariate analysis. The malignancy rate was 11.4% in the nodules with
      nondiagnostic results in the first FNA and 3.2% in the nodules with serial
      nondiagnostic results in both the first and second FNAs. CONCLUSIONS: The high
      probability of nondiagnostic results from a second FNA should be considered if a
      nodule shows cystic portion greater than 50%, nondiagnostic cytology on the first
      FNA, a nodule size<=5 mm, or hypoechogenicity. The malignancy rate of thyroid
      nodules with 2 consecutive nondiagnostic results was 3.2%.

PMID- 22395997
TI  - Nomograms for predicting the risk of arm lymphedema after axillary dissection in
      breast cancer.
AB  - BACKGROUND: Lymphedema (LE) after axillary lymph node dissection (ALND) is a
      multifactorial, chronic, and disabling condition that currently affects an
      estimated 4 million people worldwide. Although several risk factors have been
      described, it is difficult to estimate the risk in individual patients. We
      therefore developed nomograms based on a large data set. METHODS:
      Clinicopathologic features were collected from a prospective cohort comprising
      1,054 women with unilateral breast cancer undergoing ALND as part of their
      surgical treatment from August 2001 to November 2002. LE was defined as a volume
      difference of at least 200 ml between arms at 6 months or more after surgery. The
      cumulative incidence of LE was ascertained by the Kaplan-Meier method, and Cox
      proportional hazard models were used to predict the risk of developing LE on the
      basis of the available data at each time point: model 1, preoperatively; model 2,
      within 6 months from surgery; and model 3, at 6 months or later after surgery.
      RESULTS: The 5 year cumulative incidence of LE was 30.3%. Independent risk
      factors for LE were age, body mass index, ipsilateral arm chemotherapy infusions,
      level of ALND, location of radiotherapy field, development of postoperative
      seroma, infection, and early edema. When applied to the validation set, the
      concordance indices were 0.706, 0.729, and 0.736 for models 1, 2, and 3,
      respectively. CONCLUSIONS: The proposed nomograms can help physicians and
      patients predict the 5 year probability of LE after ALND for breast cancer. Free
      online versions of the nomograms are available at http://www.lymphedemarisk.com/
      .

PMID- 22395998
TI  - Disseminated tumor cells in the bone marrow negatively influence survival after
      resection of colorectal liver metastases.
AB  - BACKGROUND: Despite all efforts in extending the resectability rates of
      colorectal liver metastases, thus improving the prognosis of the patients, tumor
      recurrence occurs in many patients. Occult dissemination of tumor cells might
      reflect a minimal residual disease that is not eliminated by primary surgery.
      Because the prognostic effect of disseminated tumor cells (DTC) is still
      uncertain in this clinical setting, we analyzed these cells in the peripheral
      blood and bone marrow of patients undergoing hepatic resection of colorectal
      liver metastases. METHODS: In 108 patients with colorectal liver metastases, the
      presence of DTC in the peripheral blood and bone marrow was detected with CK20 RT
      PCR. Clinical data were prospectively collected, and multiple variables were
      analyzed regarding their influence on overall survival. RESULTS: DTC in the
      peripheral blood were detected in 40% of the patients. In 25% of the patients,
      DTC were detected in the bone marrow. The median follow-up was 34 months. Fifty
      nine of 108 patients died from tumor relapse. Multivariate analysis determined
      detection of DTC in the bone marrow to be an independent prognostic factors for
      overall survival (P = 0.038). CONCLUSIONS: This large series of patients with
      hepatic resection of colorectal liver metastases demonstrated that detection of
      CK20-positive DTC via RT-PCR in the bone marrow compartment negatively influences
      overall survival. The evidence of DTC in the bone marrow might serve as an
      additional individual marker to select patients for adjuvant treatment after
      liver metastases resection.

PMID- 22395999
TI  - T4N0 colon cancer has oncologic outcomes comparable to stage III in a specialized
      center.
AB  - BACKGROUND: National data indicate that patients with T4N0 colon carcinoma have
      worse oncologic outcomes than other stage II cases. Our hypothesis was that
      optimized surgical resection and lymph node staging in a specialized center could
      eliminate discrepancies in oncologic outcomes within stage II colon carcinomas.
      METHODS: Patient characteristics and outcomes after oncologically radical
      colectomy for pT4N0 were compared to control groups of T1-2N1, T3N1, and T3N0
      cases. Group comparisons were adjusted for age, American Society of
      Anesthesiologists score, tumor location, year of surgery, and duration of follow
      up. Cases with at least 12 collected lymph nodes and uninvolved resection margins
      (R0) were analyzed separately. In addition, the T4a subgroup was compared to both
      T4b cases with involvement of bowel loops and with infiltration of other organs
      or structures. RESULTS: T4N0 patients had worse oncologic outcomes than T1-2N1
      patients and were comparable to T3N1 patients, regardless of margins status or
      lymph node collection. When a T4b tumor infiltrated bowel, survival and
      recurrence rates were similar to T4a cases, while T4b tumors involving other
      organs were associated with increased recurrence rate and reduced survival.
      CONCLUSIONS: T4N0 colon carcinoma remains associated with poor oncologic
      outcomes, regardless of treatment in a specialized center. The biologic
      aggressiveness of T4N0 colon cancers and the different oncologic outcomes
      according to specific organ infiltration should be taken into consideration in
      the choice of adjuvant therapies.

PMID- 22396000
TI  - Risk factors for excess mortality in the first year after curative surgery for
      colorectal cancer.
AB  - BACKGROUND: Thirty-day mortality after surgery for colorectal cancer may vastly
      underestimate 1-year mortality. This study aimed to quantify the excess mortality
      in the first postoperative year of stage I-III colorectal cancer patients and to
      identify risk factors for excess mortality. METHODS: All 2,131 patients who were
      operated with curative intent for stage I-III colorectal cancer in the western
      region of the Netherlands between January 1, 2006, and December 31, 2008, were
      analyzed. Thirty-day mortality and relative survival were calculated. In
      addition, relative excess risk (RER) of death was estimated by a multivariable
      model. RESULTS: Thirty-day mortality was 4.9%. One-year mortality was 12.4%. Risk
      factors for excess mortality in the first postoperative year for colon cancer
      patients were emergency surgery (excess mortality 29.7%, RER 2.5, 95% confidence
      interval 2.5-5.0), a Charlson score of >1 (excess mortality 12.6%, RER 2.3, 95%
      confidence interval 1.5-3.7), stage II or III disease (excess mortality 14.9%,
      RER 3.9, 95% confidence interval 1.9-8.1), and postoperative adverse events
      (excess mortality 22.6%, RER 2.1, 95% confidence interval 1.4-3.2). CONCLUSIONS:
      The 30-day mortality rate highly underestimates the risk of dying in the first
      year after surgery, with excess 1-year mortality rates varying from 15 to 30%.
      This excess mortality was especially prominent in patients with comorbidities,
      higher stages of disease, emergency surgery, and postoperative surgical
      complications.

PMID- 22396001
TI  - HOXB9 expression promoting tumor cell proliferation and angiogenesis is
      associated with clinical outcomes in breast cancer patients.
AB  - BACKGROUND: Studies have suggested that HOXB9 expression in breast cancer cells
      promotes cellular invasiveness, metastatic ability, and tumor neovascularization
      in the surrounding tissue in in vitro and in vivo assays. These findings imply
      that HOXB9 overexpression may alter tumor-specific cell fates and the tumor
      stromal microenvironment, contributing to breast cancer progression. The
      objective of this study was to analyze whether these results could be applied to
      clinical practice. METHODS: A total of 141 consecutive, invasive ductal carcinoma
      patients who underwent surgical treatment were examined. Immunohistochemical
      staining was performed to evaluate the expression of HOXB9, Ki-67, CD31, and
      CD34, and the association of tumor proliferation and angiogenesis with HOXB9
      expression was analyzed. RESULTS: Of the 141 tumor specimens immunostained for
      HOXB9, 69 (48.9%) stained positive. Larger primary tumor size, hormone receptor
      negativity, HER2 positivity, higher nuclear grade, and number of pathologic nodal
      metastases were significant variables associated with HOXB9 expression. Notably,
      12 (92.3%) of 13 triple-negative breast cancer cases showed HOXB9 expression.
      Disease-free survival and overall survival were significantly different between
      the HOXB9-positive and HOXB9-negative groups (hazard ratio 20.714, P = 0.001; and
      hazard ratio 9.206, P = 0.003, respectively). Multivariate analysis indicated
      that HOXB9 expression was the only independent prognostic factor for disease-free
      survival (hazard ratio 15.532, P = 0.009). HOXB9-positive tumors showed a
      significant increase in the number of vasculature and the Ki-67 ratio compared
      with HOXB9-negative tumors. CONCLUSIONS: HOXB9 expression, which promotes tumor
      proliferation and angiogenesis, is a significant prognostic factor in breast
      cancer.

PMID- 22396002
TI  - Robotic versus laparoscopic resection of large adrenal tumors.
AB  - BACKGROUND: Although recent studies have shown the feasibility and safety of
      robotic adrenalectomy, an advantage over the laparoscopic approach has not been
      demonstrated. Our hypothesis was that the use of the robot would facilitate
      minimally invasive resection of large adrenal tumors. METHODS: Adrenal tumors>=5
      cm resected robotically were compared with those removed laparoscopically from a
      prospective institutional review board-approved adrenal database. Clinical and
      perioperative parameters were analyzed using t and chi-square tests. All data are
      expressed as mean+/-standard error of mean. RESULTS: There were 24 patients with
      25 tumors in the robotic group and 38 patients with 38 tumors in the laparoscopic
      group. Tumor size was similar in both groups (6.5+/-0.4 [robotic] vs 6.2+/-0.3 cm
      [laparoscopic], P=.661). Operative time was shorter for the robotic versus
      laparoscopic group (159.4+/-13.4 vs 187.2+/-8.3 min, respectively, P=.043), while
      estimated blood loss was similar (P=.147). The conversion to open rate was less
      in the robotic (4%) versus the laparoscopic (11%) group; P=.043. Hospital stay
      was shorter for the robotic group (1.4+/-0.2 vs 1.9+/-0.1 days, respectively,
      P=.009). The 30-day morbidity was 0 in robotic and 2.7% in laparoscopic group.
      Pathology was similar between groups. CONCLUSIONS: Our study shows that the use
      of the robot could shorten operative time and decrease the rate of conversion to
      open for adrenal tumors larger than 5 cm. Based on our favorable experience,
      robotic adrenalectomy has become our preferred minimally invasive surgical
      approach for removing large adrenal tumors.

PMID- 22396003
TI  - Risk factors for gastric-tube dependence following tongue reconstruction.
AB  - BACKGROUND: Postoperative dysphagia is not uncommon following significant
      glossectomy with laryngeal preservation. To develop effective treatments for this
      patient population, risk factors for postoperative dysphagia must be accurately
      identified. The objective of this retrospective study was to identify independent
      risk factors for dysphagia following microvascular tongue reconstruction.
      METHODS: We performed a retrospective chart review of 222 patients who had
      undergone microvascular tongue reconstruction after significant glossectomy with
      laryngeal preservation. The variables examined were age, sex, preoperative body
      mass index (BMI), history of radiotherapy (RT) to the neck, smoking, alcohol
      drinking, clinical tumor stage, extent of the defect (tongue, mandible, soft
      palate, and neck dissection), and postoperative RT. Postoperative dysphagia was
      defined as gastric-tube dependence for nutrition at the time of evaluation.
      Possible risk factors for gastric-tube dependence were subjected to univariate
      analysis and multivariate logistic regression. RESULTS: A total of 33 patients
      (14.9%) had dysphagia at the time of evaluation. Multivariate logistic regression
      analysis identified age>=70 years, BMI<18.5 kg/m2, and, most significantly,
      postoperative RT as significant risk factors for gastric-tube dependence after
      tongue reconstruction. Clinical tumor stage (stage IV/recurrence), subtotal or
      total glossectomy and full-thickness resection of the soft palate were identified
      as significant factors on univariate analysis but not on multivariate analysis.
      CONCLUSIONS: The present study has identified age>=70 years, BMI<18.5 kg/m2, and,
      especially, postoperative RT as significant risk factors for gastric-tube
      dependence after tongue reconstruction. These factors should be considered when
      selecting treatments for patients with advanced oral and oropharyngeal cancers.

PMID- 22396004
TI  - Comparison of patient characteristics and outcomes of contralateral prophylactic
      mastectomy and unilateral total mastectomy in breast cancer patients.
AB  - BACKGROUND: There has been an increasing trend toward contralateral prophylactic
      mastectomy (CPM) in the management of breast cancer (BCa). This study's objective
      was to compare clinicopathologic characteristics of BCa patients who elected CPM
      to those who elected unilateral total mastectomy (UTM) and to determine whether
      CPM improved survival. METHODS: Comparison was performed on 355 patients with
      stage 0-III BCa matched by age and stage who underwent mastectomy from 1995 to
      2008: 177 patients had CPM; 178 patients had UTM. Clinicopathological
      characteristics and survival outcomes were analyzed. RESULTS: Women who underwent
      preoperative MRI were twice as likely to have CPM (40.9 vs. 19.7%, P < 0.001).
      MRI identified additional suspicious foci in 45% CPM and 19% UTM. Patients with
      history of previous breast biopsies, family history, or BRCA mutation were more
      likely to choose CPM than UTM (40.1 vs. 24%, P = 0.001; 64.3 vs. 41.4%, P <
      0.001; 20.3 vs. 6.5%, P = 0.04, respectively). CPM patients elected nipple
      preservation (26 vs. 5.2%, P < 0.001) and immediate reconstruction more often
      (92.2 vs. 73.5%, P < 0.001); UTM patients were more likely to have attempted
      breast conservation prior to mastectomy (52.8 vs. 39.5%, P = 0.01). CPM
      identified occult BCa in 11 patients (6.6%), and three UTM patients (1.7%)
      developed contralateral BCa. With median follow-up of 61 months, by
      univariable/multivariable analyses, CPM did not improve overall, disease-free, or
      distant metastases-free survival. CONCLUSION: Factors that may influence choice
      of CPM included preoperative MRI, history of prior breast biopsies, immediate
      reconstruction, nipple preservation, family history, and BRCA status. Those who
      chose CPM did not have improved survival.

PMID- 22396005
TI  - Preoperative imaging of colorectal liver metastases after neoadjuvant
      chemotherapy: a meta-analysis.
AB  - BACKGROUND: Chemotherapy treatment induces parenchymal changes that potentially
      affect imaging of CRLM. The purpose of this meta-analysis was to provide values
      of diagnostic performance of magnetic resonance imaging (MRI), computed
      tomography (CT), fluorodeoxyglucose positron emission tomography (FDG-PET), and
      FDG-PET/CT for preoperative detection of colorectal liver metastases (CRLM) in
      patients treated with neoadjuvant chemotherapy. METHODS: A comprehensive search
      was performed for original articles published from inception to 2011 assessing
      diagnostic performance of MRI, CT, FDG-PET, or FDG-PET/CT for preoperative
      evaluation of CRLM following chemotherapy. Intraoperative findings and/or
      histology were used as reference standard. For each imaging modality we
      calculated pooled sensitivities for patients who received neoadjuvant
      chemotherapy as well as for chemonaive patients, defined as number of malignant
      lesions detected divided by number of malignant lesions as confirmed by the
      reference standard. RESULTS: A total of 11 papers, comprising 223 patients with
      906 lesions, were included. Substantial variation in study design, patient
      characteristics, imaging features, and reference tests was observed. Pooled
      sensitivity estimates of MRI, CT, FDG-PET, and FDG-PET/CT were 85.7% (69.7
      94.0%), 69.9% (65.6-73.9%), 54.5% (46.7-62.1%), and 51.7% (37.8-65.4%),
      respectively. In chemonaive patients, sensitivity rates were 80.5% (67.0-89.4%)
      for CT, 81.3% (64.1-91.4%) for FDG-PET, and 71.0% (64.3-76.9%) for FDG-PET/CT.
      Specificity could not be calculated because of non-reporting of "true negative
      lesions." CONCLUSION: In the neoadjuvant setting, MRI appears to be the most
      appropriate imaging modality for preoperative assessment of patients with CRLM.
      CT is the second-best diagnostic modality and should be used in the absence of
      MRI. Diagnostic accuracy of FDG-PET and PET-CT is strongly affected by
      chemotherapy.

PMID- 22396007
TI  - Risk factors for lymph node metastasis in pT1 and pT2 rectal cancer: a single
      institute experience in 943 patients and literature review.
AB  - BACKGROUND: Local excision has become an alternative for radical resection in
      rectal cancer for selected patients. The purpose of this study was to assess the
      clinicopathologic factors determining lymph node metastasis (LNM) in patients
      with T1-2 rectal cancer. METHODS: Between January 1995 and December 2009, a total
      of 943 patients with pT1 or pT2 rectal adenocarcinoma received radical resection
      at a single institution. Clinicopathologic factors were evaluated by univariate
      and multivariate analyses to identify risk factors for LNM. RESULTS: A total of
      943 patients (544 men and 399 women) treated for T1-2 rectal cancer were included
      in this study. LNM was found in 188 patients (19.9%). In multivariate analysis,
      lymphovascular invasion (LVI; P < 0.001, hazard ratio 11.472), poor
      differentiation (PD; P = 0.007, hazard ratio 3.218), and depth of invasion
      (presence of pT2; P = 0.032, hazard ratio 1.694) were significantly related to
      nodal involvement. The incidence for LNM lesions in the presence of LVI, PD, and
      pT2 was 68.8, 50.0, and 23.1%, respectively, while that for pT1 carcinomas with
      no LVI or PD was 7.5%. CONCLUSIONS: LVI, PD, and pT2 are independent risk factors
      predicting LNM in pT1-2 rectal carcinoma.

PMID- 22396006
TI  - Induction chemoradiotherapy followed by surgical resection for clinical T3 or T4
      locally advanced non-small cell lung cancer.
AB  - PURPOSE: To examine the usefulness of trimodality therapy in patients with
      clinical T3 or T4 (cT3-4) locally advanced non-small cell lung cancer (LA-NSCLC).
      METHODS: Between 1997 and 2009, a total of 76 LA-NSCLC patients with cT3-4
      underwent surgery. Among them, 36 patients underwent induction chemoradiotherapy
      with docetaxel and cisplatin plus concurrent radiation followed by surgery (IC
      group). The other 40 patients initially underwent surgery (IS group). The
      outcomes of the IC and IS groups were then investigated. To minimize possible
      biases caused by confounding treatment indications, we performed a retrospective
      cohort analysis by applying a propensity score (PS). Patients were divided into
      three groups according to PS tertiles, and comparisons between the IC and IS
      groups were made by PS tertile-stratified Cox proportional hazard models.
      RESULTS: For the entire cohort, which had a median follow-up duration of 48
      months, the 3- and 5-year overall survival rates were 83.8 and 78.9%,
      respectively, in the IC group, versus 66.8 and 56.5%, respectively, in the IS
      group (P = 0.0092). After adjustments for potentially confounding variables, the
      IC group continued to have a significantly longer overall survival than the IS
      group (P = 0.0045). In addition, when the analysis was limited to 52 patients
      with cT3-4N0 or N1 disease, the IC group had a significantly longer overall
      survival than the IS group after adjustments for confounding variables (P =
      0.019). CONCLUSIONS: Our study indicates that trimodality therapy is highly
      effective in patients with cT3-4 LA-NSCLC.

PMID- 22396008
TI  - Pancreatic neuroendocrine tumors: radiographic calcifications correlate with
      grade and metastasis.
AB  - BACKGROUND: Studies to identify preoperative prognostic variables for pancreatic
      neuroendocrine tumor (PNET) have been inconclusive. Specifically, the prevalence
      and prognostic significance of radiographic calcifications in these tumors
      remains unclear. METHODS: From 1998 to 2009, a total of 110 patients with well
      differentiated PNET underwent surgical resection at our institution. Synchronous
      liver metastases present in 31 patients (28%) were addressed surgically with
      curative intent. Patients with high-grade PNET were excluded. The presence of
      calcifications in the primary tumor on preoperative computed tomography was
      recorded and correlated with clinicopathologic variables and overall survival.
      RESULTS: Calcifications were present in 16% of patients and were more common in
      gastrinomas and glucagonomas (50%), but never encountered in insulinomas.
      Calcified tumors were larger (median size 4.5 vs. 2.3 cm, P=0.04) and more
      commonly associated with lymph node metastasis (75 vs. 35%, P=0.01), synchronous
      liver metastasis (62 vs. 21%, P<0.01), and intermediate tumor grade (80 vs. 31%,
      P<0.01). On multivariate analysis of factors available preoperatively,
      calcifications (P=0.01) and size (P<0.01) remained independent predictors of
      lymph node metastasis. Overall survival after resection was significantly worse
      in the presence of synchronous liver metastasis (5-year, 64 vs. 86%, P=0.04), but
      not in the presence of radiographic calcifications. CONCLUSIONS: Calcifications
      on preoperative computed tomography correlate with intermediate grade and lymph
      node metastasis in well-differentiated PNET. This information is available
      preoperatively and supports the routine dissection of regional lymph nodes
      through formal pancreatectomy rather than enucleation in calcified PNET.

PMID- 22396010
TI  - Evaluation of pathological effects in broilers during fumonisins and clays
      exposure.
AB  - This study was conducted to evaluate the possible protector effect of bentonite
      and zeolite in Bovans chicks fed a diet containing 59 mg kg(-1) of fumonisin B1
      (FB1) during 3 weeks. A total of 200 one-day-old male chicks were treated varying
      the amount of bentonite and zeolite. Chick weight was registered weekly. At the
      end of the experiment, all the chicks were killed, and the livers were analyzed
      for gross examination and histopathological changes. Plasmatic activity of
      alanine amino transferase and aspartate amino transferase (AST) were also
      determined. Sphinganine and the sphinganine-to-sphingosine ratio in serum were
      evaluated. Both, bentonite and zeolite showed a protector effect against FB1
      adsorption in the digestive tract of chicks. Chicks fed with FB1-contaminated
      feed, amended either with zeolite or bentonite, were heavier, and no macroscopic
      lesions were observed in the livers. AST activity might be considered as an
      indicator for FB1 exposition because AST levels were affected when only FB1 was
      present in the basal diet. These results indicate that both, zeolite and
      bentonite can be added into feed to diminish the effects of FB1.

PMID- 22396013
TI  - [High proliferation of An. gambiae and An. funestus larvae in irrigated and non
      irrigated rice fields in the Western forest region of Cote-d'Ivoire].
AB  - Entomological surveys were conducted in the forest region of western Cote
      d'Ivoire from November 1998 to December 1999 in order to study the ecology of
      mosquito breeding sites and bioecology of Culicidae. Three following agro-systems
      were considered: landscaped lowland (R0), the lowland with one growing season of
      rice per year (R1) and the lowland with two seasonal production of irrigated rice
      field per year (R2). Two villages were selected by agro-system, and cross
      sectional entomological surveys were conducted every six weeks in each village. A
      total of 5,839 larvae of mosquitoes were collected in the different categories of
      breeding sites surveyed. From these larvae, 2,199 imagos emerged, giving an
      emergence rate equal to 37.7%. Nine species belonging to three genera were
      identified. The genus Anopheles with 1,828 larvae represented 83.1% of the total.
      Five anophelinae species were identified. An. ziemanni was the most abundant
      species with 751 larvae (32.5% of the total). An. funestus with 531 larvae
      represented 24.1% of the total. Larvae from this species were collected in river
      with raised vegetation and in irrigated rice field at transplanting and cut
      stages. About 559 larvae of An. gambiae representing 25.4% of the total were
      collected from artificial breeding sites, particularly in rice fields after the
      planting stage. Additionally, 38,626 anthropophilic mosquitoes were collected on
      936 mannight catches in the study area. Thirty species belonging to seven genera
      were identified in the three agro-systems. In the villages of the agro-system R0,
      2,675 mosquitoes were collected on landing catches. In the villages of the agro
      ecosystem R1, 11,311 mosquitoes were collected, which was 4.2 higher than the
      number collected in the village of agro-system R0 for the same sampling effort.
      In the village of the agro-system R2, 24,640 mosquitoes were collected, which was
      9.2 higher than the number collected in the agro-system R0 and 2.2 higher than
      the number collected in the agro-system R1. In the villages of agrosystems R0, R1
      and R2, An. gambiae represented respectively 72.1%, 56% and 58.3% of anophelinae
      species collected, whereas An. funestus represented 25.6%, 40% and 31.9% of
      anophelinae species collected, in the same agrosystems, respectively. These
      results showed that areas of irrigated rice fields favoured the development of
      larvae from An. gambiae and An. funestus.

PMID- 22396011
TI  - Glucose-induced beta cell dysfunction in vivo in rats: link between oxidative
      stress and endoplasmic reticulum stress.
AB  - AIMS/HYPOTHESIS: Endoplasmic reticulum (ER) stress has been implicated in glucose
      induced beta cell dysfunction. However, its causal role has not been established
      in vivo. Our objective was to determine the causal role of ER stress and its link
      to oxidative stress in glucose-induced beta cell dysfunction in vivo. METHODS:
      Healthy Wistar rats were infused i.v. with glucose for 48 h to achieve 20 mmol/l
      hyperglycaemia with or without the co-infusion of the superoxide dismutase
      mimetic tempol (TPO), or the chemical chaperones 4-phenylbutyrate (PBA) or
      tauroursodeoxycholic acid (TUDCA). This was followed by assessment of beta cell
      function and measurement of ER stress markers and superoxide in islets. RESULTS:
      Glucose infusion for 48 h increased mitochondrial superoxide and ER stress
      markers and impaired beta cell function. Co-infusion of TPO, which we previously
      found to reduce mitochondrial superoxide and prevent glucose-induced beta cell
      dysfunction, reduced ER stress markers. Similar to findings with TPO, co-infusion
      of PBA, which decreases mitochondrial superoxide, prevented glucose-induced beta
      cell dysfunction in isolated islets. TUDCA was also effective. Also similar to
      findings with TPO, PBA prevented beta cell dysfunction during hyperglycaemic
      clamps in vivo and after hyperglycaemia (15 mmol/l) for 96 h.
      CONCLUSIONS/INTERPRETATION: Here, we causally implicate ER stress in
      hyperglycaemia-induced beta cell dysfunction in vivo. We show that: (1) there is
      a positive feedback cycle between oxidative stress and ER stress in glucose
      induced beta cell dysfunction, which involves mitochondrial superoxide; and (2)
      this cycle can be interrupted by superoxide dismutase mimetics as well as
      chemical chaperones, which are of potential interest to preserve beta cell
      function in type 2 diabetes.

PMID- 22396012
TI  - Induced pluripotent stem cells generated from diabetic patients with
      mitochondrial DNA A3243G mutation.
AB  - AIMS/HYPOTHESIS: The aim of this study was to generate induced pluripotent stem
      (iPS) cells from patients with mitochondrial DNA (mtDNA) mutation. METHODS: Skin
      biopsies were obtained from two diabetic patients with mtDNA A3243G mutation. The
      fibroblasts thus obtained were infected with retroviruses encoding OCT4 (also
      known as POU5F1), SOX2, c-MYC (also known as MYC) and KLF4. The stem cell
      characteristics were investigated and the mtDNA mutation frequencies evaluated by
      Invader assay. RESULTS: From the two diabetic patients we isolated four and ten
      putative mitochondrial disease-specific iPS (Mt-iPS) clones, respectively. Mt-iPS
      cells were cytogenetically normal and positive for alkaline phosphatase activity,
      with the pluripotent stem cell markers being detectable by immunocytochemistry.
      The cytosine guanine dinucleotide islands in the promoter regions of OCT4 and
      NANOG were highly unmethylated, indicating epigenetic reprogramming to
      pluripotency. Mt-iPS clones were able to differentiate into derivatives of all
      three germ layers in vitro and in vivo. The Mt-iPS cells exhibited a bimodal
      degree of mutation heteroplasmy. The mutation frequencies decreased to an
      undetectable level in six of 14 clones, while the others showed several-fold
      increases in mutation frequencies (51-87%) compared with those in the original
      fibroblasts (18-24%). During serial cell culture passage and after
      differentiation, no recurrence of the mutation or no significant changes in the
      levels of heteroplasmy were seen. CONCLUSIONS/INTERPRETATION: iPS cells were
      successfully generated from patients with the mtDNA A3243G mutation. Mutation
      rich, stable Mt-iPS cells may be a suitable source of cells for human
      mitochondrial disease modelling in vitro. Mutation-free iPS cells could provide
      an unlimited, disease-free supply of cells for autologous transplantation
      therapy.

PMID- 22396014
TI  - [Improving malaria management through Rapid Diagnostic Tests: appropriation by
      providers communities (Senegal)].
AB  - Introduced in the public health services in Senegal since 2007, Rapid Diagnostic
      Tests (RDTs) are a new technical opportunity for clinical diagnosis of malaria.
      We analyze how different categories of caregivers, who are the providers, assume
      appropriation of their professional practices. Similarly, we document, from the
      analysis of their application for care, attitudes of recipients towards RDTs. The
      results show a time lag between the uses of this tool and the recommendations.
      RDTs have a recognized epidemiological usefulness. However, their positive
      integration requires a change in behaviors that caregivers and recipients are not
      always willing to assume. Indeed, the architecture, working conditions and
      applications for care influence the modes of appropriation of this technical
      innovation.

PMID- 22396015
TI  - Pharmacological rescue of the mutant cystic fibrosis transmembrane conductance
      regulator (CFTR) detected by use of a novel fluorescence platform.
AB  - Numerous human diseases arise because of defects in protein folding, leading to
      their degradation in the endoplasmic reticulum. Among them is cystic fibrosis
      (CF), caused by mutations in the gene encoding the CF transmembrane conductance
      regulator (CFTR ), an epithelial anion channel. The most common mutation,
      F508del, disrupts CFTR folding, which blocks its trafficking to the plasma
      membrane. We developed a fluorescence detection platform using fluorogen
      activating proteins (FAPs) to directly detect FAP-CFTR trafficking to the cell
      surface using a cell-impermeant probe. By using this approach, we determined the
      efficacy of new corrector compounds, both alone and in combination, to rescue
      F508del-CFTR to the plasma membrane. Combinations of correctors produced additive
      or synergistic effects, improving the density of mutant CFTR at the cell surface
      up to ninefold over a single-compound treatment. The results correlated closely
      with assays of stimulated anion transport performed in polarized human bronchial
      epithelia that endogenously express F508del-CFTR. These findings indicate that
      the FAP-tagged constructs faithfully report mutant CFTR correction activity and
      that this approach should be useful as a screening assay in diseases that impair
      protein trafficking to the cell surface.

PMID- 22396016
TI  - Glaucoma-induced degeneration of retinal ganglion cells prevented by hypoxic
      preconditioning: a model of glaucoma tolerance.
AB  - Like all cells, neurons adapt to stress by transient alterations in phenotype, an
      epigenetic response that forms the basis for preconditioning against acute
      ischemic injury in the central nervous system. We recently showed that a modified
      repetitive hypoxic preconditioning (RHP) regimen significantly extends the window
      of ischemic tolerance to acute retinal ischemic injury from days to months. The
      present study was undertaken to determine if this uniquely protracted
      neuroprotective phenotype would also confer resistance to glaucomatous
      neurodegeneration. Retinal ganglion cell death at somatic and axonal levels was
      assessed after both 3 and 10 wks of sustained intraocular hypertension in an
      adult mouse model of inducible, open-angle glaucoma, with or without RHP before
      intraocular pressure elevation. Loss of brn3-positive ganglion cell soma after 3
      wks of experimental glaucoma, along with increases in several apoptotic
      endpoints, were all significantly and robustly attenuated in mice subjected to
      RHP. Soma protection by RHP was also confirmed after 10 wks of intraocular
      hypertension by brn3 and SMI32 immunostaining. In addition, quantification of
      axon density in the postlaminar optic nerve documented robust preservation in RHP
      treated mice, and neurofilament immunostaining also revealed preconditioning
      induced improvements in axon integrity/survival in both retina and optic nerve
      after 10 wks of experimental glaucoma. This uniquely protracted period of
      phenotypic change, established in retinal ganglion cells by the activation of
      latent antiapoptotic, prosurvival mechanisms at both somatic and axonal levels,
      reflects a novel form of inducible neuronal plasticity that may provide
      innovative therapeutic targets for preventing and treating glaucoma and other
      neurodegenerative diseases.

PMID- 22396018
TI  - Propranolol improves impaired hepatic phosphatidylinositol 3-kinase/akt signaling
      after burn injury.
AB  - Severe burn injury is associated with induction of the hepatic endoplasmic
      reticulum (ER) stress response. ER stress leads to activation of c-Jun N-terminal
      kinase (JNK), suppression of insulin receptor signaling via phosphorylation of
      insulin receptor substrate 1 and subsequent insulin resistance. Marked and
      sustained increases in catecholamines are prominent after a burn. Here, we show
      that administration of propranolol, a nonselective beta1/2 adrenergic receptor
      antagonist, attenuates ER stress and JNK activation. Attenuation of ER stress by
      propranolol results in increased insulin sensitivity, as determined by activation
      of hepatic phosphatidylinositol 3-kinase and Akt. We conclude that catecholamine
      release is responsible for the ER stress response and impaired insulin receptor
      signaling after burn injury.

PMID- 22396017
TI  - Toll-like receptor 4 engagement inhibits adenosine 5'-monophosphate-activated
      protein kinase activation through a high mobility group box 1 protein-dependent
      mechanism.
AB  - Despite the potent antiinflammatory effects of pharmacologically induced
      adenosine 5'-monophosphate kinase (AMPK) activation on Toll-like receptor 4
      (TLR4)-induced cellular activation, there is little evidence that AMPK is
      activated during inflammatory conditions. In the present studies, we examined
      mechanisms by which TLR4 engagement may affect the ability of AMPK to become
      activated in neutrophils and macrophages under in vitro conditions and in the
      lungs during lipopolysaccharide (LPS)-induced acute lung injury. We found that
      incubation of neutrophils or macrophages with LPS diminished the ability of 5
      aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) or hydrogen peroxide
      (H(2)O(2)) to activate AMPK. Although ratios of AMP to adenosine 5'-triphosphate
      (ATP) were increased in LPS-treated neutrophils and in the lungs of LPS exposed
      mice, a condition that should result in AMPK activation, no activation of AMPK
      was found. Immunocytochemistry and Western blot analysis revealed that nuclear to
      cytosolic translocation of the proinflammatory mediator high mobility group box 1
      protein (HMGB1) correlated with inhibition of AMPK activation in LPS-stimulated
      macrophages. Moreover, while induced overexpression of HMGB1 resulted in
      inhibition of AMPK activation, Small interfering RNA (siRNA)-induced knockdown of
      HMGB1 was associated with enhanced activation of AMPK in macrophages incubated
      with AICAR. Increased interaction between liver kinase B1 (LKB1), an upstream
      activator of AMPK, and HMGB1 was found in LPS-stimulated macrophages and in the
      lungs of mice exposed to LPS. These results suggest that nuclear to cytoplasmic
      translocation of HMGB1 in TLR4-activated cells potentiates inflammatory responses
      by binding to LKB1, thereby inhibiting the antiinflammatory effects of AMPK
      activation.

PMID- 22396019
TI  - Erythropoietin attenuates neurological and histological consequences of toxic
      demyelination in mice.
AB  - Erythropoietin (EPO) reduces symptoms of experimental autoimmune
      encephalomyelitis in rodents and shows neuroregenerative effects in chronic
      progressive multiple sclerosis. The mechanisms of action of EPO in these
      conditions with shared immunological etiology are still unclear. Therefore, we
      used a model of toxic demyelination allowing exclusion of T cell-mediated
      inflammation. In a double-blind (for food/injections), placebo-controlled,
      longitudinal four-arm design, 8-wk-old C57BL/6 mice (n = 26/group) were assigned
      to cuprizone-containing (0.2%) or regular food (ground chow) for 6 wks. After 3
      wks, mice were injected every other day with placebo or EPO (5,000 IU/kg
      intraperitoneally) until the end of cuprizone feeding. Half of the mice were
      exposed to behavioral testing, magnetic resonance imaging (MRI) and histology
      immediately after treatment cessation, whereas the other half were allowed a 3-wk
      treatment-free recovery. Immediately after termination of cuprizone feeding, all
      toxin-exposed mice were compromised regarding vestibulomotor
      function/coordination, with EPO-treated animals performing better than placebo.
      Likewise, ventricular enlargement after cuprizone, as documented by MRI, was less
      pronounced upon EPO. After a 3-wk recovery, remarkable spontaneous improvement
      was observed in all mice with no measurable further benefit in the EPO group
      ("ceiling effect"). Histological analysis of the corpus callosum revealed
      attenuation by EPO of the cuprizone-induced increase in microglial numbers and
      amyloid precursor protein accumulations as a readout of inflammation and axonal
      degeneration. To conclude, EPO ameliorates neurological symptoms in the cuprizone
      model of demyelination, possibly by reduction of inflammation-associated axonal
      degeneration in white matter tracts. These findings underscore the value of
      future therapeutic strategies for multiple sclerosis based on EPO or EPO
      variants.

PMID- 22396020
TI  - Prime-boost vaccination with rBCG/rAd35 enhances CD8+ cytolytic T-cell responses
      in lesions from Mycobacterium tuberculosis-infected primates.
AB  - To prevent the global spread of tuberculosis (TB) infection, a novel vaccine that
      triggers potent and long-lived immunity is urgently required. A plasmid-based
      vaccine has been developed to enhance activation of major histocompatibility
      complex (MHC) class I-restricted CD8+ cytolytic T cells using a recombinant
      Bacille Calmette-Guerin (rBCG) expressing a pore-forming toxin and the
      Mycobacterium tuberculosis (Mtb) antigens Ag85A, 85B and TB10.4 followed by a
      booster with a nonreplicating adenovirus 35 (rAd35) vaccine vector encoding the
      same Mtb antigens. Here, the capacity of the rBCG/rAd35 vaccine to induce
      protective and biologically relevant CD8+ T-cell responses in a nonhuman primate
      model of TB was investigated. After prime/boost immunizations and challenge with
      virulent Mtb in rhesus macaques, quantification of immune responses at the single
      cell level in cryopreserved tissue specimen from infected organs was performed
      using in situ computerized image analysis as a technological platform.
      Significantly elevated levels of CD3+ and CD8+ T cells as well as cells
      expressing interleukin (IL)-7, perforin and granulysin were found in TB lung
      lesions and spleen from rBCG/rAd35-vaccinated animals compared with BCG/rAd35
      vaccinated or unvaccinated animals. The local increase in CD8+ cytolytic T cells
      correlated with reduced expression of the Mtb antigen MPT64 and also with
      prolonged survival after the challenge. Our observations suggest that a
      protective immune response in rBCG/rAd35-vaccinated nonhuman primates was
      associated with enhanced MHC class I antigen presentation and activation of CD8+
      effector T-cell responses at the local site of infection in Mtb-challenged
      animals.

PMID- 22396021
TI  - Individual-based model of Chironomus riparius population dynamics over several
      generations to explore adaptation following exposure to uranium-spiked sediments.
AB  - Natural populations are chronically exposed to various pollutants over many
      generations. It is thus crucial to understand and quantify adaptive dynamics of
      stressed populations in order to increase the relevance of ecotoxicological risk
      assessment. However, long-term consequences to population exposure are not much
      studied yet. The present study investigated evolutionary responses of Chironomus
      riparius populations exposed to uranium (heavy metal pollutant) and to assess the
      underlying mechanisms. To fulfil our objective, we produced data with organisms
      exposed to four relevant concentrations of uranium through eight successive
      generations. We built an individual-based (IBM) model of C. riparius population
      dynamics to analyse these data and to test several assumptions about the
      mechanisms involved in the phenotypic changes. The IBM was based on a dynamic
      energy budget (DEB) model for C. riparius by Pery et al. (2002). DEB models
      account mathematically for the acquisition and use of energy to describe and
      predict growth, maintenance, development and reproduction of living organisms.
      The IBM accounted for the influence of the test conditions on the observations
      over eight generations and highlighted some trait evolution such as time to
      emergence and adult size in control conditions. The model was then used to
      analyse the exposed population data. Our results showed that exposure to uranium
      led to a phenotypic selection via a differential survival characterised by longer
      time to emergence and smaller larval maximal size. As a general conclusion, IBMs
      based on DEB-based modelling developed to analyse multi-generation experiments
      are very promising for understanding and quantifying long term selection and
      tolerance mechanisms in a population under toxic stress.

PMID- 22396022
TI  - The stressful life events and Parkinson's disease: a case-control study.
AB  - A case-control study was conducted in order to investigate the possible link
      between stressful life events and Parkinson's disease (PD). A group of 110
      consecutive newly diagnosed PD cases treated at the Institute of Neurology,
      Faculty of Medicine, Belgrade University, was compared with a control group
      comprising 220 subjects with degenerative joint disease and some diseases of the
      digestive tract. The case and control subjects were matched by sex, age (+/-2
      years) and place of residence (urban/rural). According to conditional
      multivariate logistic regression analysis, PD was found to be significantly
      related to retirement (odds ratio--OR 18.73, 95% confidence interval--95%CI 1.9
      175.4), birth of own child (OR 66.22, 95%CI 8.3-526.3) and air raids (OR 5.66,
      95%CI 2.4-13.5). The risk of PD significantly increased with the number of
      stressful events. The results of the present study support the hypothesis that
      stress may play a role in the development of PD.

PMID- 22396023
TI  - Investigation of the presence of endogenous prednisolone in equine urine by high
      performance liquid chromatography mass spectrometry and high-resolution mass
      spectrometry.
AB  - RATIONALE: After the detection of low concentrations of prednisolone in racehorse
      urine samples collected at Italian racetracks, a study was initiated to
      investigate the accuracy of the analytical protocol used and the possible
      endogenous origin of detected prednisolone. METHODS: Multiple reaction monitoring
      (MRM) MS(2) acquisition with a triple quadrupole (n = 780) and full scan MS(2)
      and MS(3) (n = 180) acquisition with a linear ion trap were checked. As a further
      confirmation, ten urine samples were analysed by high-resolution mass
      spectrometry (HRMS). RESULTS: The study showed the difficulty of identifying
      prednisolone, probably due to interfering compounds with the same molecular
      weight (360 Da) present in the matrix. The characteristic transitions for
      prednisolone were identified, both in MS(2) and MS(3), as the ions 187 and 280;
      the ion 295 was also used for identification. The concentrations detected with
      the triple quadrupole and the linear ion trap were not statistically different.
      The exact mass of prednisolone formiate (the adduct acting as a molecular ion)
      was identified by HRMS. CONCLUSIONS: The very high frequency of prednisolone
      detection in the samples (78.5%), the low concentration of this steroid and,
      importantly, the narrow range of the 95% confidence limits (0.97-1.05 in MS(2)
      mode and 0.88-1.04 in MS(3) mode), could represent evidence that its presence is
      endogenous. In the light of these results, this hypothesis seems the most
      probable, even if further studies are required to confirm it. Furthermore, a
      microbiological origin (i.e. fermentation of cortisol after sample collection)
      could not be disregarded.

PMID- 22396024
TI  - High sensitivity steroid analysis using liquid chromatography/solvent-assisted
      inlet ionization mass spectrometry.
AB  - RATIONALE: Steroids can be injected to behave as therapeutic agents to promote
      muscle growth and strength. Areas of concern include synthetic steroids in
      consumer meat and milk products and the presence of anabolic steroids in
      athletes. Here we demonstrate a new ionization method for high sensitivity
      steroid analysis using liquid chromatography/mass spectrometry (LC/MS). METHODS:
      Solvent-assisted inlet ionization (SAII) mass spectrometry was coupled directly
      to an infusion pump or to a liquid chromatograph to determine the limits of
      detection and quantitation for selected steroids. LC/MS/MS data was acquired on a
      quadrupole time-of-flight (QTOF) mass spectrometer and high resolution-accurate
      mass LC/MS data was obtained on an Orbitrap mass spectrometer. RESULTS: The SAII
      limit of detection for infusion into the Orbitrap using high mass resolution and
      accurate mass was shown, for the steroids studied, to be low ppqt and the limit
      of quantitation using LC/MS was low ppt. Low ppb levels were detected with high
      signal-to-noise from spiked urine using a simple Ziptip procedure without sample
      concentration. CONCLUSIONS: LC/SAII-MS is more sensitive than electrospray
      ionization (ESI) at similar mobile phase flow rates for the analysis of steroids.
      Previous studies have shown LC/SAII-MS to have high sensitivity for analysis of
      peptides. The combined results suggests this easy to implement ionization method
      may advantageously replace ESI for a wide range of analyses.

PMID- 22396025
TI  - A mass spectrometric investigation of isomers of butane.
AB  - RATIONALE: Butane is an important industrial chemical in which photo-processes
      are very important for the initiation of reactions. Recent advances in nanosecond
      pulsed laser technology have led to high laser intensities being available to
      researchers to enable these photo-processes to be studied in compounds such as
      butane. METHODS: The photo-decomposition, dissociation and combustion mechanisms
      in the neutral butane molecule have been studied in detail, by investigating the
      multiphoton (MP) dissociative ionisation of its n- and i-isomers, using a time-of
      flight mass spectrometer connected to a high power nanosecond laser system. The
      laser used was a Nd:Yag with a 5 ns pulse width operated at the fundamental
      wavelength (1064 nm) and the doubled and tripled wavelengths (532 nm and 355 nm).
      The fragmentation patterns for the isomers were determined for the three
      wavelengths as a function of laser intensity. Similar laser intensities of
      between 10(10) and 10(13) W/cm(2) were used at the three wavelengths: 1064, 532
      and 355 nm. RESULTS: The mass spectra of each isomer of the butane molecule
      display a very weak molecular ion and are dominated by fragment ion peaks. The
      degree of fragmentation increases as the laser intensity increases. CONCLUSIONS:
      Depending on the wavelength some significant differences in the mass spectra of
      the two isomers were detected and it has been concluded that the isomerisation of
      i-butane to n-butane is a process which is faster than the duration of the laser
      pulse used.

PMID- 22396026
TI  - Identification of imine or enamine drug metabolites using online
      hydrogen/deuterium exchange and exact mass measurements.
AB  - RATIONALE: Drug metabolites that have imine or enamine partial structures cause
      extra mass-to-charge (m/z) increases in online hydrogen/deuterium exchange (HDX)
      in addition to hydroxyl or amine protons. Online HDX and exact mass measurement
      were used herein to characterize this extra increase property, and to further
      confirm proposed metabolite structures. METHODS: Metabolites of two proprietary
      compounds as well as two commercially available compounds were analyzed using
      aqueous and HDX liquid chromatography coupled with an LTQ-Orbitrap. The exact
      mass measurements of both the precursor ions and product ions were acquired
      through data-dependent acquisition and compared with theoretical values of
      proposed fragment ions. RESULTS: Analysis of exact mass measurements of
      metabolite product ions under both normal aqueous and HDX conditions led to the
      identification of the isoxazole ring opening of compound C-1, and a double-bond
      formation on the methylpyrrolidine ring of compound C-2 during biotransformation.
      In both cases, imine or enamine structures formed in the metabolites caused extra
      m/z increases upon HDX that contributed confirmatory information to the structure
      identification. The compound 3,3-diphenyl-2-ethyl-1-pyrroline also demonstrated
      that the methylene protons adjacent to the imine were exchanged during online
      HDX. CONCLUSIONS: The exchangeability of methylene protons adjacent to imine or
      enamine moieties proved to be useful to narrow down or even pinpoint the
      metabolism sites of parent drugs when high-resolution exact mass measurement and
      online HDX were used.

PMID- 22396027
TI  - Using dissociation energies to predict observability of b- and y-peaks in mass
      spectra of short peptides.
AB  - RATIONALE: Peptide identification reliability can be improved by excluding from
      analysis those m/z peaks of candidate peptides which cannot be observed in
      practice due to various physical, chemical or thermodynamic considerations. We
      propose using dissociation energies (as opposed to proton affinities) as a
      predictor of observability of different m/z peaks in spectra of short peptides.
      METHODS: Mass spectra of the tetrapeptides AAAA, AAFA, AAVA, AFAA, AVAA, AFFA,
      and AVVA were measured in the collision-induced dissociation (CID) activation
      mode on a grid of activation times 0.05 to 100 ms and normalized collision energy
      10 to 35%. The lowest energy geometries and vibrational spectra were calculated
      for the precursor ions and their charged and neutral fragments using density
      functional theory (DFT) at the TPSS/6-31G(d,p) level. Dissociation energies were
      calculated for all fragmentation channels leading to b- or y-fragments. RESULTS:
      It is demonstrated that m/z peaks observed in the mass spectra correspond to the
      fragmentation channels with the lowest dissociation energies. Using 50 kcal/mol
      as the cut-off value of dissociation energy, it was predicted that 28 out of 42
      possible peaks in the b- and y-series of the seven tetrapeptides can be observed
      in mass spectra. In the experiments, 26 b- or y-peaks were observed, all of which
      are among the 28 predicted ones. CONCLUSIONS: The use of dissociation energies
      generalizes the use of proton affinities for semi-quantitative predictions of
      relative intensities of different m/z peaks of short peptides. Further advances
      in this direction will pave the way for reliable quantitative predictions and,
      hence, for a significant improvement in robustness and accuracy of peptide and
      protein identification tools.

PMID- 22396028
TI  - A study of the ozonolysis of model lipids by electrospray ionization mass
      spectrometry.
AB  - RATIONALE: The ozonolysis of vegetable oils has been proposed as step to
      functionalise unsaturated lipids for the production of bio-based chemicals and
      materials. The observation of ozonolysis products by mass spectrometry will
      facilitate mechanistic studies that are essential for the further development of
      industrial processes based on lipid ozonolysis. METHODS: Ozonolysis of the model
      lipids methyl oleate and triolein was performed and samples were taken over a
      range of reaction times. Ozonlysis products were separated by normal and non
      aqueous reversed-phase (NARP) liquid chromatography (LC) coupled to electrospray
      ionization (ESI) mass spectrometry (MS) and tandem mass spectrometry (MS/MS)
      using a hybrid quadrupole-time of flight instrument. Post-column addition of
      ammonium acetate solutions aided ionization. Volatile reaction products were
      observed using gas chromatography/electron impact mass spectrometry (GC/MS).
      RESULTS: Secondary ozonides, reaction intermediates and previously unreported
      high molecular weight product dimers were observed as intact molecular ammonium
      ion adducts under positive ESI. The main fragment ions obtained by MS/MS were
      from cleavage of the trioxolane group, loss of fatty acyl chain and fragmentation
      between n-8 and n-9 on the fatty acyl chain. The MS/MS spectra and exact mass
      measurements explain most of the ozonolysis reaction products. CONCLUSIONS:
      LC/MS, LC/MS/MS and GC/MS results demonstrate that the products from the
      ozonolysis of the model lipids methyl oleate and triolein are consistent with
      known ozonolysis reaction pathways. LC/MS techniques using non-aqueous
      chromatography have permitted the direct observation of mono-, di- and tri-1,2,4
      triloxanes which are the secondary ozonides formed by the ozonolysis of triolein.
      It was also shown that intermediates formed during the ozonolysis of triolein can
      combine to form high molecular weight ozonide dimers.

PMID- 22396029
TI  - Identification of free radicals in oxidized and glycoxidized
      phosphatidylethanolamines by spin trapping combined with tandem mass
      spectrometry.
AB  - RATIONALE: Nonenzymatic glycation of phosphatidylethanolamines (PEs) seems to a
      have a role in angiogenesis and atherosclerosis. Glycated PEs are more easily
      oxidized, enhancing oxidative stress. This study aims to evaluate the influence
      of glycation on the formation of intermediate radical species during oxidation of
      glycated PEs. METHODS: In the present study, the radical intermediaries formed
      during the oxidation of palmitoyl-lineoyl phosphatidylethanolamine (PLPE) and
      glycated PLPE (gPLPE) were trapped using a spin trap (DMPO) and the radical
      adducts were analyzed by electrospray ionization mass spectrometry (ESI-MS) and
      tandem mass spectrometry (ESI-MS/MS). Mass spectra were acquired using a
      electrospray Q-TOF 2 mass spectrometer. RESULTS: Several spin adducts of PLPE and
      gPLPE were identified, corresponding to carbon- and oxygen-centered radicals.
      Interpretation of the MS/MS spectra showed the existence of different sites where
      radical formation occurred, at the sn-2 acyl chain, ethanolamine moiety
      (particularly in C-1) and, in the case of glycated derivatives, also in the
      glucose moiety (particularly in C-3, C-4 and C-5). CONCLUSIONS: These results
      suggested the presence of more sites susceptible to oxidation in glycated PLPE,
      which may be responsible for the increase in the oxidative reaction rate
      occurring in glycated compounds.

PMID- 22396030
TI  - A novel chemical ionization reagent ion for organic analytes: the
      aquachloromanganese(II) cation [ClMn(H2O)+].
AB  - The reactivity of ClMn(H(2)O)(+) towards small organic compounds (L) was examined
      in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. The
      organic compounds studied are aliphatic and aromatic alcohols, aliphatic amines,
      ketones, an epoxide, an ether, a thiol and a phosphine. All the reactions lead to
      the formation of the ClMn(H(2)O)(L)(+) complex, which dissociates by loss of the
      H(2)O molecule. In general, the reactions were found to occur with high
      efficiencies (>85%), indicating them to be exothermic. Electron transfer was also
      observed between ClMn(H(2)O)(+) and compounds with low ionization energies (IE),
      to form the molecular ion (L(+*)) of the analyte. Based on these observations,
      the IE of ClMn(H(2)O)(+) is approximated to be 8.1 +/- 0.1 eV. Thus, the utility
      of ClMn(H(2)O)(+) as a chemical ionization reagent in mass spectrometry is
      expected to be limited to organic compounds with IEs greater than 8 eV.

PMID- 22396032
TI  - Fragmentation investigation of seven arylnaphthalide lignans using liquid
      chromatography/tandem quadrupole time-of-flight mass spectrometry.
AB  - RATIONALE: The combination of fragmentation patterns in positive and negative ion
      modes could be helpful in understanding the structural features of these
      arylnaphthalide lignans. METHODS: Fragmentation patterns of seven arylnaphthalide
      lignans were investigated using liquid chromatography/tandem time-of-flight mass
      spectrometry, and their fragmentation pathways were comprehensively
      characterized. RESULTS: In the positive ion mode, the cleavage of the C-1'-C-7'
      bond was the most characteristic fragmentation pattern of the lignans with both
      2'-hydroxy and 4',5'-methylenedioxy groups on the B ring. Arylnaphthalide lignans
      containing a methylenedioxy group on the B ring could lose C(2)H(2)O(2) easily.
      The characteristic mass losses of 58 Da (C(2)H(2)O(2)) could indicate the
      presence of a methylenedioxy group on the B ring. In the negative ion mode, the
      type of substituents at C-7 could affect the cleavage pattern of the lactone
      ring. CONCLUSIONS: In search for new compounds, and also in quality control,
      there is a need to have reliable methodology for the analysis of arylnaphthalide
      lignans. These results should be useful in the analysis of natural products with
      similar substructures from Chinese herbs in the future.

PMID- 22396031
TI  - The use of parallel segmented outlet flow columns for enhanced mass spectral
      sensitivity at high chromatographic flow rates.
AB  - RATIONALE: Speed of analysis is a significant limitation to current high
      performance liquid chromatography/mass spectrometry (HPLC/MS) and ultra-high
      pressure liquid chromatography (UHPLC)/MS systems. The flow rate limitations of
      MS detection require a compromise in the chromatographic flow rate, which in turn
      reduces throughput, and when using modern columns, a reduction in separation
      efficiency. Commonly, this restriction is combated through the post-column
      splitting of flow prior to entry into the mass spectrometer. However, this
      results in a loss of sensitivity and a loss in efficiency due to the post-extra
      column dead volume. METHODS: A new chromatographic column format known as
      'parallel segmented flow' involves the splitting of eluent flow within the column
      outlet end fitting, and in this study we present its application on a HPLC
      electrospray ionization time-of-flight mass spectrometer. RESULTS: Using parallel
      segmented flow, column flow rates as high as 2.5 mL/min were employed in the
      analysis of amino acids without post-column splitting to the mass spectrometer.
      Furthermore, when parallel segmented flow chromatography columns were employed,
      the sensitivity was more than twice that of conventional systems with post-column
      splitting when the same volume of mobile phase was passed through the detector.
      CONCLUSIONS: These finding suggest that this type of column technology will
      particularly enhance the capabilities of modern LC/MS enabling both high
      throughput and sensitive mass spectral detection.

PMID- 22396033
TI  - On-stage liquid-phase lipid microextraction coupled to nanospray mass
      spectrometry for detailed, nano-scale lipid analysis.
AB  - RATIONALE: Developments in instrumentation aimed at microscopic sampling have led
      to an emphasis on applications analyzing small volumes and molecular
      concentrations within biological, chemical, and industrial samples. Simultaneous
      improvements in the sensitivity and versatility of nanospray mass spectrometers
      have made it possible to directly couple these sampling and analysis processes.
      METHODS: We developed a versatile liquid-phase lipid microextraction (LPME)
      technique for nanoliter to microliter volumes that is amenable to direct
      nanospray mass spectrometry (NMS). Lipophilic analytes within several types of
      biological samples were extracted and analyzed by partitioning and concentrating
      the analytes based on their solubility within two immiscible or partially
      miscible liquid phases. RESULTS: The utility of LPME-NMS is demonstrated by
      extracting and analyzing molecules in four different types of applications: (1)
      visualization of an extracted neutral lipid-specific fluorescent dye from an
      aqueous solvent; (2) identification of controlled acid-catalyzed hydrolysis of
      triacylglycerols within nanospray capillaries; (3) reproducible sampling of a
      fatty acid emulsion; and (4) profiling of diverse lipids in a complex biological
      matrix of rabbit serum. CONCLUSIONS: The modified instrumentation of a multi
      port, on-stage bioworkstation shows considerable versatility by combining
      nanomanipulation, microextraction and direct NMS for a variety of chemical,
      biological, industrial, and clinical applications.

PMID- 22396034
TI  - Study of matrix-induced effects in multi-residue determination of pesticides by
      online gel permeation chromatography-gas chromatography/mass spectrometry.
AB  - RATIONALE: Multi-residue determination of pesticides in a complex matrix by
      online gel permeation chromatography-gas chromatography/mass spectrometry (GPC
      GC/MS) is increasingly concerned for its high throughput, efficiency and
      accuracy. Study of matrix-induced suppression or enhancement of the instrument
      signals is important for the application of this technique. METHODS: Matrix
      suppression and enhancement effects for 176 pesticides were studied by online GPC
      GC/MS and post-extraction addition. Suppression effects induced by co-eluted
      compounds were examined in the matrices tea and human breast milk. The prepared
      matrix was studied to confirm the results by deliberate addition of phthalates or
      caffeine to the matrix of Chinese cabbage. RESULTS: Both suppression and
      enhancement effects induced by co-eluted matrix were found. The different results
      may depend on the concentration of the matrix. Enhancement effects for carbamate
      and polar pesticides were found because of the blocking of active sites in the
      instrument by the large volume injection (LVI) technique combined with on-column
      and programmed temperature vaporization (PTV) mode. The results can explain the
      significant difference in instrument signals between isomers or native and
      isotope labels in some matrices. CONCLUSIONS: Online GPC-GC/MS with combined PTV
      and on-column LVI mode is presumed to be applicable for the multi-residue method
      including the studied pesticides if calibrated by matrix-matched standards.
      However, further cleanup steps should be deloped to remove co-eluted matrix if
      remarkable suppression effects are found.

PMID- 22396035
TI  - Development of a methodology using gas chromatography-combustion-isotope ratio
      mass spectrometry for the determination of the carbon isotope ratio of caffeine
      extracted from tea leaves (Camellia sinensis).
AB  - RATIONALE: Compound-specific isotope analysis (CSIA) of the extracted caffeine
      can be used to determine the authenticity of the origin of tea. Elemental
      analysis-isotope ratio mass spectrometry (EA-IRMS), which is widely used to
      measure the carbon isotope ratio of caffeine, has a strict requirement for the
      purity of the extracted caffeine. To obtain high-purity caffeine from tea leaves,
      the conventional extraction process has to be repeated and usually takes about 5
      6 h. To improve the measurement of the carbon isotope ratio of caffeine, a more
      rapid and accurate measuring method is needed. METHODS: An analytical protocol
      was developed for the determination of the carbon isotope ratio of caffeine from
      tea leaves using gas chromatography-combustion-isotope ratio mass spectrometry
      (GC-C-IRMS) combined with our extraction process. The procedure to extract
      caffeine and determine its carbon isotope ratio takes around 1.5 h. RESULTS: The
      standard deviation of the method is less than 0.10/00 (1sigma). The measured
      carbon isotope ratios were not influenced by the amount of caffeine injected
      (0.08-0.62 ug) or by the extraction yield of caffeine from the tea leaves.
      CONCLUSIONS: The carbon isotope ratios of caffeine from eight tea cultivars were
      determined using the protocol.

PMID- 22396036
TI  - Detection of isocyanates and polychlorinated biphenyls using proton transfer
      reaction mass spectrometry.
AB  - RATIONALE: Isocyanates are highly reactive species widely used in industry. They
      can cause irritation of the eyes, trigger asthma, etc. Polychlorinated biphenyls
      (PCBs) were widely used in electrical equipments like capacitors and transformers
      in the last century and are still present in the environment today. PCBs are
      known to cause cancer and to affect the immune, reproductive, nervous and
      endocrine systems. Therefore, there is a need for a simple, rapid and reliable
      analytical method for the detection of traces of isocyanates and of PCBs.
      METHODS: The data presented in this paper were obtained using a proton transfer
      reaction (PTR) time-of-flight mass spectrometer and a high sensitivity PTR
      quadrupole mass spectrometer. We also utilized a recently developed direct
      aqueous injection (DAI) inlet system for proton transfer reaction mass
      spectrometry (PTR-MS) instruments that allows the analysis of trace compounds in
      liquids. RESULTS: We detected four isocyanates in the headspace above small
      sample quantities and investigated their fragmentation pathways to obtain a
      fundamental understanding of the processes involved in proton transfer reactions
      and also to determine the best operating conditions of the PTR-MS instruments. In
      addition, nine PCBs were unambiguously identified via their exact mass and
      isotopic distribution and detected in different concentration levels via direct
      injection of the liquid. CONCLUSIONS: Utilizing recent developments and
      improvements in PTR-MS, we can rapidly detect two important environmental
      pollutant compound classes (isocyanates and PCBs) at high accuracy and without
      any sample preparation. In this paper, we provide proof of the detection of
      traces of isocyanates and PCBs in air and also of PCBs in liquids. These results
      could be used for the development of a real-time monitoring device for industrial
      waste, polluted air or water quality surveillance.

PMID- 22396037
TI  - Proton-transfer reaction mass spectrometry (PTRMS) in combination with thermal
      desorption (TD) for sensitive off-line analysis of volatiles.
AB  - RATIONALE: When performing trace gas analysis, it is not always possible to bring
      the source of volatiles and the gas analyzer together. In these cases, volatile
      storage containers, such as thermal desorption (TD) tubes, can be used for off
      line measurement. TD is routinely combined with gas chromatography/mass
      spectrometry (GC/MS), but so far not with proton-transfer reaction mass
      spectrometry (PTRMS), which has a faster response. METHODS: A PTR-quadrupole-MS
      instrument and a PTR-ion-trap-MS instrument were separately coupled to a TD unit
      for off-line analysis of trace volatiles in air. Carbograph 1TD/Carbopack X
      sorbent tubes were filled with different concentrations of a trace gas mixture
      containing low molecular weight volatiles (32 g/mol up to 136 g/mol) and measured
      with the above-mentioned combinations. The carrier gas in the TD unit was changed
      from helium to nitrogen to be able to combine this instrument with the mass
      spectrometer. RESULTS: Good linearity and reproducibility with the amount of gas
      stored were obtained. The storage capacity over time (up to 14 days) showed
      larger variability (<11% for all compounds, except for acetone 27%). Several
      tubes were filled with breath of different persons, and the breath of a smoker
      showed increased levels of acetonitrile and benzene. The combination of the PTR
      ion-trap instrument with the TD unit was also investigated. Due to its higher
      sampling rate, the ion-trap system showed higher throughput capabilities than the
      quadrupole system. CONCLUSIONS: The combination of TD with PTRMS using both a
      quadrupole and an ion trap for off-line volatile analysis has been validated. TD
      tubes can be a robust and compact volatile storage method when the mass
      spectrometry and the sampling cannot be performed in the same place, for example
      in large screening studies. In addition, a higher measurement throughput than
      with GC/MS could be obtained.

PMID- 22396038
TI  - Stable isotope switching (SIS): a new stable isotope probing (SIP) approach to
      determine carbon flow in the soil food web and dynamics in organic matter pools.
AB  - RATIONALE: Recent advances in stable isotope probing (SIP) have allowed direct
      linkage of microbial population structure and function. This paper details a new
      development of SIP, Stable Isotope Switching (SIS), which allows the simultaneous
      assessment of carbon (C) uptake, turnover and decay, and the elucidation of soil
      food webs within complex soils or sedimentary matrices. METHODS: SIS utilises a
      stable isotope labelling approach whereby the (13)C-labelled substrate is
      switched part way through the incubation to a natural abundance substrate. A
      (13)CH(4) SIS study of landfill cover soils from Odcombe (Somerset, UK) was
      conducted. Carbon assimilation and dissimilation processes were monitored through
      bulk elemental analysis isotope ratio mass spectrometry and compound-specific gas
      chromatography/combustion/isotope ratio mass spectrometry, targeting a wide range
      of biomolecular components including: lipids, proteins and carbohydrates.
      RESULTS: Carbon assimilation by primary consumers (methanotrophs) and sequential
      assimilation into secondary (Gram-negative and -positive bacteria) and tertiary
      consumers (Eukaryotes) was observed. Up to 45% of the bacterial membrane lipid C
      was determined to be directly derived from CH(4) and at the conclusion of the
      experiment ca. 50% of the bulk soil C derived directly from CH(4) was retained
      within the soil. CONCLUSIONS: This is the first estimate of soil organic carbon
      derived from CH(4) and it is comparable with levels observed in lakes that have
      high levels of benthic methanogenesis. SIS opens the way for a new generation of
      SIP studies aimed at elucidating total C dynamics (incorporation, turnover and
      decay) at the molecular level in a wide range of complex environmental and
      biological matrices.

PMID- 22396039
TI  - Pretargeted radioimmunotherapy (pRAIT) in medullary thyroid cancer (MTC).
AB  - Prognosis of medullary thyroid carcinoma (MTC) varies from long- to short-term
      survival, based on prognostic factors, such as serum calcitonin doubling time (Ct
      DT). Pretargeted radioimmunotherapy (pRAIT) is a novel targeted radionuclide
      therapy, using a bispecific monoclonal antibody (BsMAb) and a radiolabeled
      bivalent hapten, designed to improve the therapeutic index and to deliver
      increased tumor-absorbed doses to relatively radioresistant solid tumors.
      Pretargeting has demonstrated a more favorable therapeutic index and clinical
      efficacy than directly labeled anti-carcinoembryonic antigen (CEA) MAb in
      preclinical MTC models. Moreover, two phase I/II clinical trials assessing anti
      CEA * anti-DTPA-indium BsMAb (murine F6x734 and chimeric hMN14x734) with (131)I
      di-DTPA-indium showed encouraging therapeutic results in progressive, metastatic,
      MTC patients, with an improved survival in intermediate- and high-risk (pre-pRAIT
      Ct DT, <2 years) patients, as compared to contemporaneous untreated patients
      (median overall survival, 110 months vs 61 months; P < 0.030). pRAIT efficacy has
      been recently confirmed in a prospective multicenter phase II study assessing
      hMN14x734 and (131)I-di-DTPA-indium in rapidly progressive MTC patients. New
      pRAIT compounds are now available with fully humanized, recombinant, trivalent
      BsMAb (anti-CEA TF2) and histamine-succinyl-glutamine (HSG) peptides. The HSG
      peptide allows easy and stable labeling with different radiometals, such as
      (177)Lu or (90)Y beta-emitters having favorable physical features for pRAIT or
      (68)Ga and (18)F positron-emitters, allowing the development of a highly
      sensitive and specific immuno-positron emission tomography method in MTC or other
      CEA-positive tumors.

PMID- 22396040
TI  - Meta-analyses of the associations between four common TGF-beta1 genetic
      polymorphisms and risk of colorectal tumor.
AB  - The associations between four common genetic polymorphisms of transforming growth
      factor-beta1 (TGF-beta1 -509 C > T, +869 T > C, +915 G > C, and -800 G > A) and
      risk of colorectal tumor (including adenoma and cancer) have been widely studied.
      To date, no conclusions could be available because of controversial results
      reported. Thus, we conducted a meta-analysis to further assess the associations.
      We searched the databases of Medline, Embase, and Wangfang to identify eligible
      studies, and latest update was on January 1, 2012. Odds ratio (OR) and 95%
      confidence interval (95%CI) were calculated to present the associations. Our meta
      analysis indicated that TGF-beta1 -509 C > T, +869 T > C, +915 G > C, and -800 G
      > A were not associated with risk of colorectal adenoma (OR = 0.89 for C carriers
      vs. TT for -509 C > T, 1.03 for C carriers vs. TT for +869 T > C, 1.09 for C
      carriers vs. GG for +915 G > C, and 1.19 for A carriers vs. GG for 800 G > A).
      However, C allele of TGF-beta1 -509 C > T and A allele of -800 G > A were
      associated with increased risk of colorectal cancer (CRC), and OR (95%CI) was
      1.23 (0.99-1.52) for CC vs. TT for -509 C > T and 6.64 (3.46-12.72) for A
      carriers vs. GG. The positive association between -509 C allele and risk of CRC
      was more obvious when subgroup analyses were conducted for population-based and
      large sample-sized studies as well as Caucasians. In contrast, we did not
      observed any associations between TGF-beta1 +869 T > C, +915 G > C, and risk of
      CRC. This study indicated that C allele of TGF-beta1-509 C > T and A allele of 
      800 G > A might contribute to the increased risk of CRC, and could be used as two
      of genetic marks for screening individuals at high risk of CRC. Because of modest
      limitation, large sample-sized studies were required to confirm the findings.

PMID- 22396041
TI  - Pretargeting: taking an alternate route for localizing radionuclides.
AB  - Bispecific antibody pretargeting is a two-step procedure for selectively
      delivering radionuclides to tumors. The procedure was developed to solve a number
      of problems encountered when radionuclides are directly coupled to an IgG, such
      as slow blood clearance and delayed tumor accretion. While various forms of
      antibody fragments can reduce blood pool activity and provide faster tumor
      localization, tumor uptake is reduced considerably. In pretargeting procedures,
      the radionuclide is attached to a small molecule that quickly traverses the
      vascular barrier to reach the tumor cells, achieving maximum accretion within 0.5
      to 1.0 h. Just as quickly, it is eliminated from the body, thereby minimizing
      tissue exposure and developing high tumor/tissue ratios very early. In order to
      capture the radionuclide in the tumor, a bispecific antibody (bsMAb) that binds
      to the tumor and to the isotope carrier (e.g., a hapten-peptide) is pre
      administered some time earlier. The pretargeting procedure has been shown
      repeatedly to improve tumor localization as compared to directly radiolabeled
      antibodies, thereby enhancing both imaging and therapy. In this article, we
      review the progress our group has made toward developing and testing bsMAb
      pretargeting systems for cancer detection and therapy.

PMID- 22396042
TI  - Association between FTO gene polymorphism and cancer risk: evidence from 16,277
      cases and 31,153 controls.
AB  - A recent genome-wide association study showed that the rs9939609 polymorphism in
      the fat mass and obesity-associated (FTO) gene was associated with body mass
      index (BMI)/obesity in Europeans. Subsequently, several studies have investigated
      the association between FTO polymorphism and cancer risk. However, the results
      have been inconsistent. In this study, a meta-analysis was performed to clarify
      the association between FTO polymorphism and cancer risk. Published literature
      from PubMed and Embase databases were retrieved. Pooled odds ratio (OR) with 95 %
      confidence interval (CI) was calculated using fixed-effects model. A total of 13
      studies involving 16,277 cases and 31,153 controls were identified. The results
      suggested that FTO rs9939609 polymorphism was not significantly associated with
      the increased risk of cancer (OR = 1.01, 95 %CI 0.98-1.04), with the exception
      that a statistically significant association was found for pancreatic cancer (OR
      = 1.10, 95 %CI 1.03-1.19). No publication bias was detected (Begg's test: P =
      0.760; Egger's test: P = 0.553). Our meta-analysis indicated that there was no
      association between FTO rs9939609 polymorphism and the increased risk of cancer,
      although this polymorphism was marginally associated with pancreatic cancer.
      However, the conclusion should be made with caution since most included studies
      did not take BMI/obesity into account.

PMID- 22396043
TI  - Describing the highly three dimensional Right Ventricle flow.
AB  - Visualization of the three-dimensional flow within the Right Ventricle (RV) is a
      challenging issue due to the fully three-dimensional geometry of the ventricular
      cavity. To date proper characterization and quantification of the RV flow still
      remains incomplete, and techniques that can be easily applied to current medical
      imaging are scarce. A method for simulating the highly complex, multi directional
      flow within the RV is presented by coupling 4D echocardiography imaging with
      numerical simulations based on the Immersed Boundaries Method (IBM). A novel
      formulation for accurately computing the space-time distribution of the blood
      residence time inside the cavity is introduced. Results showed an initial compact
      vortex forming past the tricuspid orifice at early diastole that quickly breaks
      into a weakly turbulent flow pattern and rearranges, during systole, into a
      peculiar stream-wise vortex spinning out towards the pulmonary orifice. This
      arrangement is maintained when the Ejection Fraction (EF) is reduced from 58 to
      32%. The average blood transit time is found to scale almost inversely
      proportional to the EF. A careful analysis of the residence time permitted to
      assess the relative significance of the different flow components (from the
      direct flow, with a residence time less than one heartbeat, to the residual
      volume, that stagnates in the ventricle) and their distribution in space.

PMID- 22396044
TI  - A benzamide-linked small molecule NDMC101 inhibits NFATc1 and NF-kappaB activity:
      a potential osteoclastogenesis inhibitor for experimental arthritis.
AB  - PURPOSE: Using receptor activator of NF-kappaB ligand (RANKL) induced osteoclast
      differentiation on RAW264.7 as a screening tool; we synthesize and identify small
      molecule inhibitors preserving immunomodulatory effects as therapeutics for
      rheumatoid arthritis. METHODS: Differentiation into osteoclast-like cells was
      examined by tartrate-resistant acid phosphatase (TRAP) staining and expression of
      osteoclast differentiation markers. Collagen-induced arthritis (CIA) mice were
      administered test articles by gavages to assess its efficacy. Then clinical,
      histological, and biochemical parameters were assessed to determine the effects
      of N-(4-chloro-2-fluorophenyl)-2-hydroxybenzamide (NDMC101) on synovial
      inflammation and bone erosion by hematoxlin and eosin staining and Enzyme-linked
      immunosorbent assay (ELISA). RESULTS: NDMC101 markedly inhibited RANKL-induced
      formation of TRAP+ multinucleated cells in RAW264.7 and bone marrow macrophage
      cells (BMMs). Moreover, pit formation assay showed that NDMC101 significantly
      reduced the bone-resorbing activity of mature osteoclasts. In CIA mice, oral
      administration of NDMC101 reduced arthritic index and mitigated bone erosion.
      Serum TNF-alpha and IL-1beta concentrations in these mice were decreased
      significantly at the higher dose of 62.5 mg/kg. CONCLUSIONS: Screening of our
      chemical library, our findings suggest that NDMC101 inhibits osteoclastogenesis
      which also ameliorates paw swelling and inflammatory bone destruction. Its
      efficacy is associated with the inhibition of such transcription factors as NF
      kappaB and NFATc1 as well as multiple protein kinases, including p38, ERK, and
      JNK. There results guarantee further clinical tests of NDMC101 for its
      therapeutic potential in the treatment of inflammation-induced bone diseases.

PMID- 22396046
TI  - Utilization and intensity of outpatient care related to military sexual trauma
      for veterans from Afghanistan and Iraq.
AB  - Little research has examined factors associated with the utilization of
      outpatient health care services related to sexual assault experiences. The
      Veterans Health Administration provides free outpatient treatment services to
      veterans who report military sexual trauma (MST); this system provides a unique
      opportunity to examine factors related to the utilization of mental health and
      non-mental health outpatient services by patients with sexual trauma. The current
      study examined sociodemographic, military service factors, and primary diagnoses
      related to utilization and utilization intensity of MST-related care among 4,458
      Operation Enduring Freedom/Operation Iraqi Freedom Veterans in a 1-year period
      after reporting an experience of MST. Of the veterans who reported MST, 75.9%
      received MST-related care. The most notable factor that influenced receipt and
      intensity of MST-related care was gender, where male veterans used less care than
      female veterans. These results have important treatment implications for both
      veteran and civilian sexual trauma survivors.

PMID- 22396047
TI  - Becoming an evidence-based service provider: staff perceptions and experiences of
      organizational change.

PMID- 22396048
TI  - Primary and behavioral healthcare integration: threat or opportunity for
      addiction treatment organizations?

PMID- 22396045
TI  - Macrophages from nonobese diabetic mouse have a selective defect in IFN-gamma but
      not IFN-alpha/beta receptor pathway.
AB  - PURPOSE: Aberrant regulation of innate immune cells such as macrophages has been
      implicated in the onset and progression of type 1 diabetes (T1D). Macrophages
      from nonobese diabetic (NOD) mouse, an animal model of T1D, entail developmental
      and functional defects that are often associated with hypo-responsiveness to
      interferon (IFN)-gamma. We aimed to uncover a mechanism underlying this
      phenomenon. METHODS: We analyzed the receptor pathway along with the response of
      macrophages exposed to IFN-gamma and the related IFNs such as IFN-alpha/beta.
      RESULTS: We found that NOD macrophages failed to fully respond to IFN-gamma but
      not to IFN-alpha for the production of inflammatory cytokines (e.g. TNF-alpha and
      IL-12). NOD macrophages were also resistant to apoptotic pathway induced by IFN
      gamma and LPS. Analyses of receptor pathway revealed that STAT1 pathway of
      intracellular signaling was selectively impaired in NOD macrophages exposed to
      IFN-gamma but not to IFN-alpha/beta. Further, these defects correlated with a low
      phosphorylation level of JAK2, and were related to impaired up-regulation of
      surface IFN-gamma receptor 2 (IFN-gammaR2) by IFN-gamma. CONCLUSION: Taken
      together, our results suggest that NOD macrophages have a selective defect in IFN
      gamma but not IFN-alpha/beta receptor pathway. As IFN-gamma and IFN-alpha have
      been implicated in the development of autoimmunity towards beta-cells, such an
      unanticipated selectivity in IFN responsiveness may provide a new insight into
      the pathogenesis of T1D.

PMID- 22396049
TI  - Musculoskeletal injuries among hospital patient care staff before and after
      implementation of patient lift and transfer equipment.
AB  - OBJECTIVE: Using an observational research design and robust surveillance data,
      we evaluated rates of musculoskeletal (MS) injuries, days away from work, and
      restricted work days among patient care staff at a medical center and community
      hospital in the United States over 13 years, during which time a "minimal manual
      lift" policy and mechanical lift equipment were implemented. METHODS: Workers'
      compensation claims data were linked to human resources data to define outcomes
      of interest and person-time at risk to calculate rates. Poisson and negative
      binomial regression with lagging were used to compare outcome rates in different
      windows of time surrounding the intervention. Patterns of MS injuries associated
      with patient-handling were contrasted to patterns of other MS injuries that would
      not be affected by the use of mechanical lift equipment. RESULTS: At the medical
      center, no change in the patient-handling MS injury rate followed the
      intervention. A 44% decrease was observed at the community hospital. At both
      hospitals, the rate of days away declined immediately - before it was reasonable
      for the intervention to have been adopted. CONCLUSIONS: Institutional-level
      changes at the time of the intervention likely influenced observed results with
      findings only partially consistent with an intervention effect. Observational
      studies can be useful in assessing effectiveness of safety interventions in
      complex work environments. Such studies should consider the process of
      intervention implementation, the time needed for intervention adoption, and the
      dynamic nature of work environments.

PMID- 22396050
TI  - Systematic review and meta-analysis of antibiotic prophylaxis to prevent
      infections from chest drains in blunt and penetrating thoracic injuries (Br J
      Surg 2012; 99: 506-513).

PMID- 22396051
TI  - Randomized clinical trial of bilateral subtotal thyroidectomy versus total
      thyroidectomy for Graves' disease with a 5-year follow-up (Br J Surg 2012; 99:
      515-522).

PMID- 22396052
TI  - Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis
      (Br J Surg 2012; 99: 532-539).

PMID- 22396053
TI  - Resuscitative emergency thoracotomy in a Swiss trauma centre (Br J Surg 2012; 99:
      541-548).

PMID- 22396054
TI  - Unresectable colorectal cancer liver metastases treated by intraoperative
      radiofrequency ablation with or without resection.

PMID- 22396055
TI  - Effects of tirapazamine on experimental colorectal liver metastases after
      radiofrequency ablation (Br J Surg 2012; 99: 567-575).

PMID- 22396056
TI  - Liver resection for colorectal cancer metastases involving the caudate lobe (Br J
      Surg 2011; 98: 1476-1482).

PMID- 22396059
TI  - High tie in anterior resection for rectal cancer confers no increased risk of
      anastomotic leakage (Br J Surg 2012; 99: 127-132).

PMID- 22396060
TI  - Clinical significance of liver ischaemia after pancreatic resection (Br J Surg
      2011; 98: 1760-1765).

PMID- 22396063
TI  - HPLC quantitative analysis of insecticidal didehydrostemofoline and stemofoline
      in Stemona collinsiae root extracts.
AB  - INTRODUCTION: Stemona spp. have been traditionally used as natural pesticides and
      medicinal plants. Stemona collinsiae Craib has been of interest for its
      insecticidal activity, which has been supported by many scientific research
      studies. The roots contain didehydrostemofoline and stemofoline alkaloids as
      active components. OBJECTIVE: To develop and validate a HPLC method for the
      quantitative analysis of didehydrostemofoline and stemofoline in S. collinsiae
      root extracts. METHODOLOGY: HPLC was carried out using a Hypersil BDS C18-column
      eluted with methanol:1 m m ammonium acetate (55:45) with a flow rate of 1 mL/min
      and detection at 295 nm. Method validation was performed to assure its linearity,
      precision, accuracy and limits of detection and quantitation. RESULTS:
      Didehydrostemofoline and stemofoline showed a linear relationship within the
      range of 0.5-432.4 and 0.5-188.4 ug/mL, respectively. The method was shown to be
      precise with RSD < 2%. The average recovery of didehydrostemofoline and
      stemofoline were 98.80 and 99.97%, respectively. Eight samples of S. collinsiae
      root extracts were analysed and the average contents of didehydrostemofoline and
      stemofoline were 0.78 and 0.048% w/w, respectively. CONCLUSION: The HPLC method
      developed was appropriate for the analysis of didehydrostemofoline and
      stemofoline in S. collinsiae root extracts. This work would be useful as a guide
      for the standardisation of S. collinsiae root extract raw materials and their
      products as natural pesticides.

PMID- 22396065
TI  - Mycobacterium kansasii pulmonary infection: CT findings in 29 cases.
AB  - PURPOSE: Our aim was to assess computed tomography (CT) features of Mycobacterium
      kansasii pulmonary infection (M. kansasii infection). MATERIALS AND METHODS: A
      total of 29 cases confirmed to have M. kansasii infections were analyzed. The
      main locations of pulmonary changes, incidence, and various imaging features of
      the cavity (location, maximum diameter, wall thickness, satellite nodules,
      intracavitary fluid), and other imaging findings such as nodules, consolidation,
      and bronchiectasis, were visually assessed on CT images. RESULTS: Locations of
      the main abnormalities were as follows: right S2 41%; right S1 31%; left S1+S2 2:
      21%. A total of 49 cavities were observed in 24 (83%) cases. The mean maximum
      diameter, wall thickness, and ratio of wall thickness to the maximum diameter
      were 33.0 mm, 4.7 mm, and 0.19, respectively. Shapes of the cavities were round
      in nine (18.4%), oval in 17 (34.7%), and tubular/meandering in 23 (47%).
      Satellite nodules were found in only 30.6% of patients (n = 15). Small nodules
      were found in 26 (89.7%) patients, and most of them showed a centrilobular
      distribution. CONCLUSION: The characteristic CT findings suggestive of M.
      kansasii infection include cavities located in the right posterior or apical
      segment with a tubular/meandering shape and a thin wall.

PMID- 22396064
TI  - Birth weight and perceived stress reactivity in older age.
AB  - Stress reactivity is a disposition that underlies individual differences in
      stress responses, thereby affecting vulnerability for the development of disease.
      Besides genetic and early postnatal environmental factors, stress reactivity has
      been shown to be influenced by an adverse prenatal developmental environment, but
      it is unclear if such effects persist into older age. We tested associations
      between fetal growth and perceived stress reactivity in 421 participants from the
      Hertfordshire Cohort at age 66-75 years. Regression analysis showed a U-shaped
      association between birth weight and perceived stress reactivity with increased
      levels of stress reactivity at the lower and upper end of the birth weight
      distribution. These effects were stable after adjustment for markers of early
      adversity and recent adversity and chronic stress. Although the effects were
      small, they are consistent with findings from studies in younger cohorts, and
      demonstrate that such effects can persist into older age.

PMID- 22396066
TI  - Establishment and clinical application of a highly sensitive enzyme immunoassay
      for determination of N-acetyl-seryl-aspartyl-lysyl-proline.
AB  - N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a natural inhibitor of
      pluripotent hematopoietic stem cell proliferation and is normally found in human
      plasma. Because AcSDKP is hydrolyzed by the N-terminal active site of angiotensin
      converting enzyme and partially eliminated in urine, its plasma level is a result
      of a complex balance between its production, hydrolysis by ACE, and renal
      elimination. In this study, we attempted to establish an enzyme immunoassay (EIA)
      for quantifying AcSDKP-like immunoreactive substance (IS), which is applicable
      for monitoring plasma AcSDKP levels in healthy subjects and patients with chronic
      renal failure. Using beta-D-galactosidase-labeled Gly-gammaAbu-SDKP as a marker
      antigen, an anti-rabbit IgG-coated immunoplate as a bound/free separator and 4
      methylumbelliferyl-beta-D-galactopyranoside as a fluorogenic substrate, a highly
      sensitive and specific EIA was developed for the quantification of AcSDKP-IS in
      human plasma. The lower limit of quantification was 0.32 fmol/well, and the sharp
      inhibition competitive EIA calibration curve obtained was linear between 8.0 and
      513 fmol/ml. This EIA was so sensitive that only 10 ul plasma sample was required
      for a single assay. The coefficients of variation (reproducibility) for human
      plasma concentrations of 0.2 and 2.1 pmol/ml were 7.2 and 7.7%, respectively, for
      inter-assay and 13.3 and 7.8% for intra-assay comparisons. Plasma AcSDKP-IS level
      was significantly higher in patients with chronic renal failure (0.92 +/- 0.39
      pmol/ml) compared with healthy subjects (0.29 +/- 0.07 pmol/ml). These results
      suggest that our EIA may be useful to evaluate plasma AcSDKP level as a biomarker
      in various patients.

PMID- 22396067
TI  - Critical role of hyperthermic intraperitoneal chemoperfusion in the treatment of
      a patient with Pseudomyxoma peritonei.
AB  - The role of hyperthermic intraperitoneal chemoperfusion (HIPEC) in the treatment
      of Pseudomyxoma peritonei is debated by clinicians. We report the case of a
      patient who had multiple episodes of short-interval disease recurrence following
      debulking surgery, and only achieved long-term remission with the addition of
      HIPEC. A review of the relevant literature is presented.

PMID- 22396068
TI  - Changes in the soft-bottom macrobenthic diversity and community structure from
      the ports of Mumbai, India.
AB  - Soft-bottom macrobenthic diversity and community structure were assessed at
      Mumbai and Jawaharlal Nehru ports during three different periods between 2001 and
      2002 (November 2001 post-monsoon 1, April/May 2002 pre-monsoon, and October 2002
      post-monsoon 2). A total of 43 macrobenthic invertebrate species belonging to
      five phyla were recorded. Macrofaunal abundance (PM1 186, PreM 106, and PM2 31
      ind m(-2)) and species diversity index (PM1 0.87, PreM 0.73, and PM2 0.30) were
      very low in all the seasons. Polychaetes were the most dominant macrobenthic
      group (72.09%) followed by decapoda, amphipoda, and bivalves (4.56%). Canonical
      correspondence analysis showed that sediment texture, temperature, and suspended
      particulate matter were the most important environmental variables influencing
      polychaete species composition. Significant seasonal variations were observed,
      influenced by dissimilar monsoonal patterns. Macrobenthic population density
      during November 2001 was higher than that of October 2002 post-monsoon season.
      Pre-monsoon season recorded more carnivorous polychaete species than post-monsoon
      seasons. The present study showed lower values of polychaete diversity index in
      all the seasons compared to earlier studies. Out of 31 polychaete species, 19
      have been reported for the first time from this area. Polychaete species and
      Glycera longipinnis, Paraprionospio pinnata, and Cossura coasta recorded from
      1985 to 1986 were also observed in the present study. Species like Sigambra
      constricta, Perinereis cavifrons, Prionospio polybranchiata, and Parheteromastus
      tenuis were not recorded in the present study, although they were observed during
      earlier studies in this area.

PMID- 22396069
TI  - Heavy metal enrichment in the seagrasses of Lakshadweep group of islands--a
      multivariate statistical analysis.
AB  - An assessment on heavy metal (Al, Cd, Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb and Zn)
      accumulation by seven seagrass species of Lakshadweep group of islands was
      carried out using multivariate statistical tools like principal component
      analysis (PCA) and cluster analysis (CA). Among all the metals, Mg and Al were
      determined in higher concentration in all the seagrasses, and their values varied
      with respect to different seagrass species. The concentration of the four toxic
      heavy metals (Cd, Pb, Zn and Cu) was found higher in all the seagrasses when
      compared with the background values of seagrasses from Flores Sea, Indonesia. The
      contamination factor of these four heavy metals ranged as Cd (1.97-12.5), Cu
      (0.73-4.40), Pb (2.3-8.89) and Zn (1.27-2.787). In general, the Pollution Load
      Index (PLI) calculated was found to be maximum for Halophila decipiens (58.2).
      Results revealed that Halophila decipiens is a strong accumulator of heavy
      metals, followed by Halodule uninervis and Halodule pinifolia, among all the
      tested seagrasses. Interestingly, the small-leaved seagrasses were found to be
      efficient in heavy metal accumulation than the large-leaved seagrass species.
      Thus, seagrasses can better be used for biomonitoring, and seagrasses can be used
      as the heavy metal sink as the biomass take usually long term to get remineralize
      in nature.

PMID- 22396070
TI  - Preliminary occurrence studies of antibiotic residues in Hong Kong and Pearl
      River Delta.
AB  - An improved liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was
      developed and validated to investigate the occurrence of selected antibiotic
      residues in Hong Kong and Pearl River Delta. LC and MS parameters were optimized
      to produce the maximum analytical responses for each compound. The established
      method targeted five groups of antibiotics, namely, macrolides, sulfonamides,
      tetracyclines, quinolones, and amphenicols. The method was validated for three
      types of environmental water matrices, namely, reservoir, river, and estuarine
      waters. Low detection limits of 0.17-0.18 ng/L for macrolides, 0.22-0.34 ng/L for
      quinolones, 0.67-1.65 ng/L for tetracyclines, and 0.27-0.56 ng/L for sulfonamides
      were obtained. No apparent interferences were observed in the chromatograms of
      all antibiotics groups. The developed method was preliminarily used to analyze
      water samples collected from Yuen Long River in New Territories, Hong Kong and
      four sites along the Pearl River Delta. Results showed that high level of
      tetracycline was found among the groups tested in the local river samples. In
      Pearl River Delta, we identified significant levels of erythromycin,
      roxithromycin, and sulfadiazine in Shenzhen Reservoir.

PMID- 22396071
TI  - Dose dense 1 week on/1 week off temozolomide in recurrent glioma: a retrospective
      study.
AB  - Alternative temozolomide regimens have been proposed to overcome O(6)
      methylguanine-DNA methyltransferase mediated resistance. We investigated the
      efficacy and tolerability of 1 week on/1 week off temozolomide (ddTMZ) regimen in
      a cohort of patients treated with ddTMZ between 2005 and 2011 for the progression
      of a glioblastoma during or after chemo-radiation with temozolomide or a
      recurrence of another type of glioma after radiotherapy and at least one line of
      chemotherapy. Patients received ddTMZ at 100-150 mg/m(2)/d (days 1-7 and 15-21 in
      cycles of 28-days). All patients had a contrast enhancing lesion on MRI and the
      response was assessed by MRI using the RANO criteria; complete and partial
      responses were considered objective responses. Fifty-three patients were
      included. The median number of cycles of ddTMZ was 4 (range 1-12). Eight patients
      discontinued chemotherapy because of toxicity. Two of 24 patients with a
      progressive glioblastoma had an objective response; progression free survival at
      6 months (PFS-6) in glioblastoma was 29%. Three of the 16 patients with a
      recurrent WHO grade 2 or 3 astrocytoma or oligodendroglioma or oligo-astrocytoma
      without combined 1p and 19q loss had an objective response and PFS-6 in these
      patients was 38%. Four out of the 12 evaluable patients with a recurrent WHO
      grade 2 or 3 oligodendroglioma or oligo-astrocytoma with combined 1p and 19q loss
      had an objective response; PFS-6 in these patients was 62%. This study indicates
      that ddTMZ is safe and effective in recurrent glioma, despite previous
      temozolomide and/or nitrosourea chemotherapy. Our data do not suggest superior
      efficacy of this schedule as compared to the standard day 1-5 every 4 weeks
      schedule.

PMID- 22396072
TI  - Immunohistochemical detection of IDH1 mutation, p53, and internexin as prognostic
      factors of glial tumors.
AB  - Isocitrate dehydrogenase 1 (IDH1) mutations, which are early and frequent genetic
      alterations in astrocytomas, oligodendrogliomas, oligoastrocytomas, and secondary
      glioblastomas, are specific to arginine 132 (R132). Recently, we established
      monoclonal antibodies (mAbs) against IDH1 mutations: anti-IDH1-R132H and anti
      IDH1-R132S. However, the importance of immunohistochemistry using the combination
      of those mAbs has not been elucidated. For this study, 164 cases of glioma were
      evaluated immunohistochemically for IDH1 mutations (R132H and R132S) using anti
      IDH1 mAbs (HMab-1 and SMab-1). IDH1 mutation was detected, respectively, in 9.7%,
      63.6%, 51.7%, and 77.8% of primary grade IV, secondary grade IV, grade III, and
      grade II gliomas. For each grade of glioma, prognostic factors for progression
      free survival and overall survival were evaluated using clinical and pathological
      parameters in addition to IDH1 immunohistochemistry. IDH1 mutation, p53
      overexpression, and internexin expression, as evaluated using
      immunohistochemistry with clinical parameters such as degree of surgical removal
      and preoperative Karnofsky Performance Status (KPS), might be of greater
      prognostic significance than histological grading alone in grade III as well as
      IDH1 mutation in grade IV gliomas.

PMID- 22396074
TI  - Simultaneous extraction and separation of flavonols and flavones from
      Chamaecyparis obtusa by multi-phase extraction using an ionic liquid-modified
      microsphere polymer.
AB  - INTRODUCTION: Flavonols and flavones, especially quercitrin, myricetin and
      amentoflavone, are the main anti-bacterial and anti-cancer compounds in
      Chamaecyparis obtuse. Multi-phase extraction is a new method that can extract and
      separate target compounds simultaneously. OBJECTIVE: An amino ionic liquid
      immobilised microsphere polymer was used as a multi-phase extraction sorbent to
      extract and separate quercitrin, myricetin and amentoflavone from Chamaecyparis
      obtusa. METHODOLOGY: The sorbent and Chamaecyparis obtusa powder were packed into
      a single cartridge. Using a fixed volume of methanol with five repetitions, the
      target compounds were extracted from the powder to the sorbent. The sorbent was
      then washed with n-hexane to remove any interfering species and the target
      compounds were eluted sequentially using water, methanol and methanol containing
      1% acetic acid (vol.). RESULTS: Under the optimised conditions, 0.45 mg/g of
      quercitrin, 0.18 mg/g of myricetin and 0.12 mg/g of amentoflavone from 2.0 g of
      powder were obtained by multi-phase extraction using 0.3 g of sorbent.
      CONCLUSION: The method described has a low deviation error, requires a small
      amount of solvent and is highly selective and reproducible.

PMID- 22396073
TI  - Hypoxia-inducible factor-1-regulated protein expression and oligodendroglioma
      patient outcome: comparison with established biomarkers and preoperative UCSF low
      grade scoring system.
AB  - Methods for predicting outcome for patients with oligodendrogliomas and
      anaplastic oligodendrogliomas (AOs) are limited. Hypoxia-inducible factor-1alpha
      (HIF-1alpha) controls many proteins involved in glycolysis and angiogenesis
      including VEGF, Glut-1, and CA-IX. We examined whether expression of HIF-1alpha
      and other hypoxia-regulated molecules (HRM) can predict overall (OS) and
      progression-free (PFS) survival. We correlated these data with more established
      biomarkers and a published preoperative scoring system. We prospectively
      collected tissue samples and followed outcomes of 50 patients with
      oligodendrogliomas and 32 with AOs. Tumor tissues were stained for measures of
      proliferative index, microvascular density, IDH-1 mutational status, and HRMs. We
      retrospectively analyzed preoperative imaging and clinical data based on the UCSF
      Scoring System (good prognostic indicators: Karnofsky Performance Scale (KPS)
      score > 80, age < 50 years, tumor diameter < 4 cm, noneloquent tumor location)
      and correlated these with immunohistochemical markers, 1p19q chromosomal status,
      and compared both with patient PFS and OS. Mean follow-up was 85.6 +/- 41.4
      months. HRMs showed higher expression in AOs than in oligodendrogliomas. Both
      1p19q codeletion and IDH-1 mutation predict outcome of patients with both
      oligodendroglioma and AO. The UCSF score is a strong predictor for
      oligodendrogliomas patient outcome and is strengthened by IDH-1 and 1p19q status.
      Glut-1 may be useful in predicting PFS in AOs. Proliferation index >5 for
      oligodendrogliomas and KPS <= 80 for AOs predict a worse prognosis.
      Immunohistochemical markers of HRMs show a significantly higher expression in
      anaplastic variants of oligodendrogliomas and may contribute to the prediction of
      survival in these patients.

PMID- 22396075
TI  - Expected loss functions as additional measures to assess performance of multiple
      testing procedures for combination drug dose finding.
AB  - There are several measures that are commonly used to assess performance of a
      multiple testing procedure (MTP). These measures include power, overall error
      rate (family-wise error rate), and lack of power. In settings where the MTP is
      used to estimate a parameter, for example, the minimum effective dose, bias is of
      interest. In some studies, the parameter has a set-like structure, and thus, bias
      is not well defined. Nevertheless, the accuracy of estimation is one of the
      essential features of an MTP in such a context. In this paper, we propose several
      measures based on the expected values of loss functions that resemble bias. These
      measures are constructed to be useful in combination drug dose response studies
      when the target is to identify all minimum efficacious drug combinations. One of
      the proposed measures allows for assigning different penalties for incorrectly
      overestimating and underestimating a true minimum efficacious combination.
      Several simple examples are considered to illustrate the proposed loss functions.
      Then, the expected values of these loss functions are used in a simulation study
      to identify the best procedure among several methods used to select the minimum
      efficacious combinations, where the measures take into account the investigator's
      preferences about possibly overestimating and/or underestimating a true minimum
      efficacious combination. The ideas presented in this paper can be generalized to
      construct measures that resemble bias in other settings. These measures can serve
      as an essential tool to assess performance of several methods for identifying set
      like parameters in terms of accuracy of estimation.

PMID- 22396076
TI  - Nerve growth factor-mediated neuronal plasticity in spinal cord contributes to
      neonatal maternal separation-induced visceral hypersensitivity in rats.
AB  - Visceral hyperalgesia is a multifactorial gastrointestinal disorder which
      featured with alterations of abdominal motility and/or gut sensitivity, and is
      believed to be triggered by environmental stressor or psychological factors.
      However, its etiology remains incompletely understood. In this study, we aimed to
      investigate whether nerve growth factor (NGF)-mediated neuronal plasticity is
      involved in neonatal maternal separation (NMS)-induced visceral hypersensitivity
      in adult rats, and whether NGF antagonist can attenuate or block such
      development. In our experiments, animals subjected to NMS were developed with
      visceral hyperalgesia at age of 8 weeks. The threshold for visceral pain among
      these NMS rats was remarkably lowered than that of the normal handling (NH) rats;
      however, the expression levels of NGF, c-fos, calcitonin gene-related peptide
      (CGRP), Substance P, and tyrosine kinases A (TrkA) were notably elevated in
      lumbosacral spinal cord and/or dorsal root ganglion (DRG) when comparing to those
      of the NH rats. Further, as intra-peritoneal administration of NGF (10 MUl at 1
      MUg/kg/day) was given to NH rats during neonatal period, effects that comparable
      to NMS induction were observed in the adulthood. In contrast, when NMS rats were
      treated with NGF antagonist K252a (10 MUl/day from postnatal days 2-14), which
      acts against tyrosine kinases, the neonatal stress-induced down-shifted visceral
      pain threshold was restored and neuronal activation, specifically NGF and
      neuropeptide production, was attenuated. In conclusion, our data strongly suggest
      that NGF triggers neuronal plasticity and plays a crucial role in NMS-induced
      visceral hypersensitivity in which NGF antagonism provides positive inhibition
      via blocking the tyrosine phosphorylation of TrkA.

PMID- 22396077
TI  - Intrathecal administration of NTS1 agonists reverses nociceptive behaviors in a
      rat model of neuropathic pain.
AB  - Chronic neuropathic pain arising from peripheral nerve damage is a severe
      clinical issue where there is a major unmet medical need. We previously
      demonstrated that both neurotensin (NT) receptor subtypes 1 (NTS1) and 2 (NTS2)
      are involved in mediating the naloxone-insensitive antinociceptive effects of
      neurotensin in different analgesic tests including hotplate, tail-flick, and
      tonic pain. However, the role of these receptors in neuropathic pain management
      has been poorly investigated. In the present study, we therefore examined whether
      intrathecal delivery of NTS1 agonists was effective in reducing neuropathic pain
      symptoms in rats. Neuropathy was induced by sciatic nerve constriction (CCI
      model), and the development of mechanical allodynia and thermal hyperalgesia on
      the ipsi- and contralateral hind paws was examined 3, 7, 14, 21, and 28 days post
      surgery. CCI-operated rats exhibited significant increases in thermal and
      mechanical hypersensitivities over a 28-day testing period. Spinal injection of
      NT to CCI rats alleviated the behavioral responses to radiant heat and mechanical
      stimuli, with a maximal reversal of 91% of allodynia at 6 MUg/kg. Intrathecal
      administration of the NTS1-selective agonist, PD149163 (30-90 MUg/kg) also
      produced potent anti-allodynic and anti-hyperalgesic effects in nerve-injured
      rats. Likewise, heat hyperalgesia and tactile allodynia produced by CCI of the
      sciatic nerve were fully reversed by the NTS1 agonist, NT69L (5-25 MUg/kg).
      Altogether, these results support the idea that the NTS1 receptor subtype is
      involved in pain modulation, and the potential use of NTS1 agonists for the
      treatment of painful neuropathies.

PMID- 22396078
TI  - Spontaneous burrowing behaviour in the rat is reduced by peripheral nerve injury
      or inflammation associated pain.
AB  - Pain influences many aspects of daily living and effective analgesics should
      reinstate normal spontaneous daily behaviours. Experiments are described herein
      which show that the innate, spontaneous behaviour of burrowing by rats, which can
      be simply and objectively assessed by measuring the amount of gravel left in a
      hollow tube 1 h after presentation to the rat, is reduced by peripheral nerve
      injury (tibial nerve transection (TNT), L5 spinal nerve transection (SNT) and
      partial sciatic nerve ligation (PSNL)) and also following inflammation induced by
      intra-plantar injection of Complete Freund's Adjuvant (CFA). Gabapentin (100
      mg/kg sc) but not at 30 mg/kg sc significantly reduced burrowing activity in
      naive rats. All peripheral nerve injuries and CFA reduced burrowing compared with
      shams and rats naive to surgery. The level of mechanical hypersensitivity in rats
      with peripheral nerve injury did not correlate with the deficit in burrowing
      indicating that different parameters of the holistic pain experience are measured
      in these paradigms. Gabapentin at 30 mg/kg sc, but not 100 mg/kg sc, reversed the
      deficit in burrowing induced by TNT and ibuprofen (30 mg/kg sc) reversed the
      effect of CFA on burrowing. These experiments show that measurement of burrowing
      is a simple, objective assay of innate rodent behaviour affected by pain that is
      ethologically relevant to the rat, does not rely wholly on evoking a reflex and
      can dissociate a selective analgesic dose of gabapentin from one inducing motor
      impairment in the same animal.

PMID- 22396079
TI  - Effects of perceived and exerted pain control on neural activity during pain
      relief in experimental heat hyperalgesia: a fMRI study.
AB  - Perceived control over pain can attenuate pain perception by mechanisms of
      endogenous pain control and emotional reappraisal irrespective of whether this
      control is exerted or only perceived. Self-initiated termination of pain elicits
      different expectations of subsequent pain relief as compared to perceived pain
      control. It is unknown whether and how this perceived vs. exerted control on pain
      differs and affects subsequent pain relief. Using fMRI, we studied two factors of
      pain control on pain relief: the (i) sense of control (perceived control but no
      execution) and (ii) the execution of control (exerted control). To account for
      the impact of factual execution of pain control on pain relief we applied
      bearable short and hardly bearable long contact-heat stimuli which were applied
      either controllable or not. Using controllability as factor, there was
      dissociable neural activity during pain relief: following the perceived control
      condition neural activity was found in the orbitofrontal and mediofrontal cortex
      and, following the exerted control condition, in the anterolateral and
      dorsolateral prefrontal cortex and posterior parietal cortex. We conclude that
      (i) pain controllability has an impact on pain relief and (ii) the prefrontal
      cortex shows dissociable neural activity during pain relief following exerted vs.
      perceived pain control. This might reflect the higher grade of uncertainty during
      pain relief following perceived pain control mediated by the orbitofrontal and
      medial prefrontal cortex and processes of working memory and updating
      expectations during pain relief following exerted control mediated by the lateral
      prefrontal cortex.

PMID- 22396080
TI  - Electrical low-frequency stimulation induces central neuroplastic changes of pain
      processing in man.
AB  - Electrical low-frequency stimulation (LFS) inhibits pain perception and
      nociceptive processing as shown by psychophysical and electrophysiological means
      (long-term depression, LTD). Information regarding central mechanisms involved in
      LTD induction and maintenance are still missing. This study hypothesizes that
      electrical LFS induces changes in activation pattern of pain-related brain areas.
      Thirty-two electrophysiological and psychophysical experiments were performed in
      16 healthy volunteers. Painful electrical test stimulation (0.125 Hz, 60 pulses)
      and conditioning LFS (1 Hz, 1200 pulses) were applied by a concentric electrode
      to the right hand. Test stimulation series were performed before (Pre) and after
      LFS (Post) or no stimulation period (Control). Volunteers rated pain perception
      according to a verbal rating scale (0-100). Somatosensory evoked cortical
      potentials were recorded with 64-channel electroencephalography. Individual
      dipole source modeling using CURRY software (Compumedics, Hamburg, Germany)
      yielded information about dipole location and strength. The strongest decrease in
      LFS-induced pain perception was shown after LFS (p < 0.01). Topographic
      distribution of cortical potentials revealed reproducible negative (N1, N2) and
      positive (P2) components. Dipole magnitude analysis showed a significant
      difference between Post LFS and Post Control for P2 (p < 0.01). P2 dipole
      location analysis yielded a significant posterior (p < 0.05) shift following LTD
      induction. Thus, data reveal central changes of pain processing after LTD
      induction. These experiments may help judging the potency of LTD as model for
      electrostimulation in future analgesic therapy.

PMID- 22396081
TI  - Pain sensitivity and modulation in primary insomnia.
AB  - Sleep of good quantity and quality is considered a biologically important
      resource necessary to maintain homeostasis of pain-regulatory processes. To
      assess the role of chronic sleep disturbances in pain processing, we conducted
      laboratory pain testing in subjects with primary insomnia. Seventeen participants
      with primary insomnia (mean +/- SEM 22.6 +/- 0.9 yrs, 11 women) were individually
      matched with 17 healthy participants. All participants wore an actigraph device
      over a 2-week period and completed daily sleep and pain diaries. Laboratory pain
      testing was conducted in a controlled environment and included (1) warmth
      detection threshold testing, (2) pain sensitivity testing (threshold detection
      for heat and pressure pain), and (3) tests to access pain modulatory mechanisms
      (pain facilitation and inhibition). Primary insomnia subjects reported
      experiencing spontaneous pain on twice as many days as healthy controls during
      the at-home recording phase (p < 0.05). During laboratory testing, primary
      insomnia subjects had lower pain thresholds than healthy controls (p < 0.05 for
      heat pain detection threshold, p < 0.08 for pressure pain detection threshold).
      Unexpectedly, pain facilitation, as assessed with temporal summation of pain
      responses, was reduced in primary insomnia compared to healthy controls (p <
      0.05). Pain inhibition, as assessed with the diffuse noxious inhibitory control
      paradigm (DNIC), was attenuated in insomnia subjects when compared to controls (p
      < 0.05). Based on these findings, we propose that pain-inhibitory circuits in
      patients with insomnia are in a state of constant activation to compensate for
      ongoing subclinical pain. This constant activation ultimately may result in a
      ceiling effect of pain-inhibitory efforts, as indicated by the inability of the
      system to adequately function during challenge.

PMID- 22396082
TI  - Pain evoked by pressure stimulation on the tibia bone - influence of probe
      diameter on tissue stress and strain.
AB  - The fundamental aspects of bone associated pain in humans are not fully
      understood. In this study pressure pain applied to the tibia bone was
      investigated experimentally in humans and by means of computer simulations. In
      humans, the pressure pain sensitivity and the relation between tissue indentation
      and pressure intensity were recorded by a computer-controlled pressure algometer
      with two different probe sizes (0.03 cm(2) and 1.0 cm(2)). The simulation-model
      was validated by the experimental pressure-indentation data and described tissue
      stress and strain distribution during pressure stimulation. Tissue stress and
      strain were extracted from the simulation models at the indentation equal to the
      pressure pain threshold. The pressure pain threshold was higher for the large
      compared with the small probe size (P < 0.05). This is in accordance with the
      simulation model where the strain in the interface between subcutaneous adipose
      tissue and bone was lowest with the large probe compared with the small probe
      when applying indentations similar to the pressure pain thresholds. For both
      probes the strain peaked in adipose tissue at 0.29, and in the bone interface it
      was reduced by 3% (0.03 cm(2)) and 15% (1.0 cm(2)), respectively. For both probes
      the stress peaked at 235 kPa in skin layer, and in the deeper layers it was
      reduced to 50 kPa. Mechanosensitive nociceptors innervating the periosteum are
      ideally placed to mediate pain evoked by pressure stimulation on the tibia bone
      and small diameter probes may be optimal for assessing bone associated pain
      sensitivity.

PMID- 22396083
TI  - Differential effects of lidocaine on nerve growth factor (NGF)-evoked heat- and
      mechanical hyperalgesia in humans.
AB  - We investigated the effects of a non-specific sodium channel blocker (lidocaine)
      on heat pain thresholds and mechanical impact pain at day 7 and 21 after
      intradermal injection of 1 MUg NGF. Measurements were performed in 12 healthy
      male subjects prior to and 5 min after intradermal injection of 150 MUl lidocaine
      administered at concentrations of 0.01% (~0.4 mM) and 0.1% (~4 mM) to both NGF
      and control skin sites. NGF caused a maximum reduction of heat pain thresholds at
      day 7 (NGF 42.6 +/- 0.6 vs. 49.4 +/- 0.3  degrees C in control skin). Lidocaine
      sensitized normal skin for heat pain, but reduced heat hyperalgesia after NGF at
      day 7 (44.3 +/- 0.8  degrees C, lidocaine 0.1%; p < 0.005). Pain upon supra
      threshold mechanical impact stimulation was increased after NGF at day 7 (VAS 29
      + 5) and massively enhanced at day 21 (VAS 64 + 5, p < 0.001). Lidocaine dose
      dependently attenuated mechanically-induced pain at both control and NGF-treated
      sites. Maximum lidocaine effects on mechanical hyperalgesia were recorded at day
      21 in NGF skin (pain reduction to VAS 37 +/- 4, p < 0.00001). Repetitive impact
      stimuli caused increasingly more pain at the NGF sites at day 21 and this pain
      increase was efficiently suppressed by lidocaine 0.1%. Lidocaine differentially
      affects NGF-induced mechanical hyperalgesia (analgesic effect) and heat
      sensitivity of nociceptors (sensitizing effect). These opposing responses may be
      attributed to block of sodium channels vs. sensitization of TRPV1. NGF-evoked
      extreme mechanical impact pain indicates high action potential discharge
      frequencies, which might be more susceptible to lidocaine block.

PMID- 22396084
TI  - Dose response of tramadol and its combination with paracetamol in UVB induced
      hyperalgesia.
AB  - Combining tramadol with paracetamol is an established analgesic treatment
      strategy. However, dosing and differential effects on peripheral and central
      hyperalgesia are still to be determined. After Ethics Committee approval, 32
      volunteers have been included in this 2 phased, double blinded, placebo
      controlled, cross-over study. A defined small skin area was irradiated with a UVB
      source inducing hyperalgesia. Twenty-four hours after irradiation, heat pain-,
      cold pain threshold (HPPT, CPPT), mechanical pain sensitivity to pin prick (MPS)
      in the area of pin prick hyperalgesia (AsH) and MPS in the sunburn were
      determined. In phase I, measurements have been repeated 30 min after receiving
      cumulative 0.3, 0.6 and 1 mg/kg of intravenous (i.v.) tramadol or active placebo.
      Only at 1 mg/kg tramadol and solely for MPS in the sunburn a reduction to placebo
      could be demonstrated (p = 0.024). Accordingly in phase II, the trial has been
      repeated using 1 mg/kg tramadol and paracetamol or placebo in a cumulative i.v.
      dose of 330, 660 and 990 mg. Now the addition of 330 mg paracetamol to tramadol
      reduced thermal hyperalgesia by 1.15  degrees C (CI 0.55; 1.76). This effect,
      however, did not increase with higher doses. Tramadol showed week anti
      hyperalgesia reducing CPPT, MPS and AsH compared to baseline measurements (p <
      0.05). Paracetamol also reduced secondary hyperalgesia, but no combination effect
      with tramadol could be shown. We conclude, in inflammatory hyperalgesia tramadol
      alone exerts only weak anti-hyperalgesia. Even adding a small dose paracetamol
      enhances thermal anti-hyperalgesia.

PMID- 22396086
TI  - A conservative method of testing whether combination analgesics produce additive
      or synergistic effects using evidence from acute pain and migraine.
AB  - Fixed-dose combination analgesics are used widely, and available both on
      prescription and over-the-counter. Combination drugs should provide more
      analgesia than with any single drug in the combination, but there is no evidence
      in humans about whether oral combinations have just additive effects, or are
      synergistic or even subadditive. We suggest that the measured result for the
      combination would be the summation of the absolute benefit increase (effect of
      active drug minus effect of placebo) of each component of a combination if
      effects were (merely) additive, and greater than the sum of the absolute benefits
      if they were synergistic. We tested measured effects of combination analgesics
      against the sum of the absolute benefits in acute pain and migraine using meta
      analysis where individual components and combinations were tested against placebo
      in the same trials, and verified the result with meta-analyses where individual
      components and combinations were tested against placebo in different trials.
      Results showed that expected numbers needed to treat (NNT) for additive effects
      were generally within the 95% confidence interval of measured NNTs. This was true
      for combinations of paracetamol plus ibuprofen and paracetamol plus opioids in
      acute pain, and naproxen plus sumatriptan in migraine, but not where efficacy was
      very low or very high, nor combinations of paracetamol plus dextropropoxyphene.
      There was no evidence of synergy, defined as supra-additive effects.

PMID- 22396085
TI  - Peripartum pain management in opioid dependent women.
AB  - Increased pain sensitivity and the development of opioid tolerance complicate the
      treatment of pain experiencedby opioid maintained pregnantwomenduring delivery
      and the perinatal period. Theaim of the present study was to investigate
      differences in pain management of opioid maintained compared to nondependent
      pregnant women during delivery and the postpartum period. 40 deliveries of 37
      opioid dependent women enrolled in a double-blind, double-dummy randomized
      controlled trial (RCT) examining the safety and efficacy of methadone (mean dose
      at the time of delivery = 63.89 mg) and buprenorphine (mean dose at the time of
      delivery = 14.05 mg) during pregnancy were analyzed and participants were matched
      to a non-dependent comparison group of 80 pregnant women. Differences in pain
      management (opioid and non-opioid analgesic medication) during delivery and
      perinatal period were analyzed. Following cesarean delivery opioid maintained
      women received significantly less opioid analgesics (day of delivery p = 0.038;
      day 1: p = 0.02), NSAIDs were administered more frequently to opioid dependent
      patients than to the comparison group during cesarean section and on the third
      day postpartum. Significantly higher nicotine consumption in the group of opioid
      dependentwomenhad a strong influence onthe retrieved results, and might be
      considered as an independent factor of altered pain experience. Differences in
      pain treatment became evident when comparing opioid maintained women to healthy
      controls. These differences might be based on psychosocial consequences of opioid
      addiction along with the lack of an interdisciplinary consensus on pain treatment
      protocols for opioid dependent patients.

PMID- 22396087
TI  - Painfully reassuring? The effects of validation on emotions and adherence in a
      pain test.
AB  - Communicating reassurance to patients with musculoskeletal pain complaints, but
      no red flags, presents a dilemma of dampening worry while refraining from
      reinforcing undue pain behaviors. Previous research shows that reassurance does
      not decrease negative affect and may be perceived as not taking the symptoms
      seriously. Validation offers an alternative where the patient's experiences and
      feelings are acknowledged and has demonstrated, for other problems, a decrease in
      arousal which may set the stage for behavioral change. The purpose of this study
      was to investigate experimentally whether validation, as compared to
      invalidation, impacts on emotions and adherence during repeated pain tests. To
      this end, 50 participants were randomized to either a validation or invalidation
      condition. Each participant was told they would undergo four pain trials
      involving holding a bucket at arm's length to tolerance. During the inter-trial
      interval, the experimenter provided validating or invalidating responses
      according to the randomization. As a proxy measure of adherence subjects were
      asked to engage in an additional pain test. Results indicated that validation
      relative to invalidation resulted in significantly more positive affect and
      significantly less worry. Both groups had reductions in negative affect over the
      trials, but there were no difference between the groups on negative affect or
      pain. However, adherence was more than twice as high in the validation group as
      compared to invalidation. These results show that a relatively simple validation
      procedure had significant and positive effects on emotion and increased
      adherence. Further research should extend these findings and explore their
      clinical application.

PMID- 22396088
TI  - Psychological risk factors for chronic post-surgical pain after inguinal hernia
      repair surgery: a prospective cohort study.
AB  - A significant proportion of patients experience chronic post-surgical pain (CPSP)
      following inguinal hernia surgery. Psychological models are useful in predicting
      acute pain after surgery, and in predicting the transition from acute to chronic
      pain in non-surgical contexts. This is a prospective cohort study to investigate
      psychological (cognitive and emotional) risk factors for CPSP after inguinal
      hernia surgery. Participants were asked to complete questionnaires before surgery
      and 1 week and 4 months after surgery. Data collected before surgery and 1 week
      after surgery were used to predict pain at 4 months. Psychological risk factors
      assessed included anxiety, depression, fear-avoidance, activity avoidance,
      catastrophizing, worry about the operation, activity expectations, perceived pain
      control and optimism. The study included 135 participants; follow-up
      questionnaires were returned by 119 (88.1%) and 115 (85.2%) participants at 1
      week and 4 months after surgery respectively. The incidence of CPSP (pain at 4
      months) was 39.5%. After controlling for age, body mass index and surgical
      variables (e.g. anaesthetic, type of surgery and mesh type used), lower pre
      operative optimism was an independent risk factor for CPSP at 4 months; lower pre
      operative optimism and lower perceived control over pain at 1 week after surgery
      predicted higher pain intensity at 4 months. No emotional variables were
      independently predictive of CPSP. Further research should target these cognitive
      variables in pre-operative psychological preparation for surgery.

PMID- 22396089
TI  - Widespread pain and medically certified disability pension in the Hordaland
      Health Study.
AB  - Widespread pain (WSP) is common in the general population and is associated with
      poor outcomes. The aim of this study was to quantify the risk for medically
      certified disability pension from WSP. We further studied how other common
      physical symptoms, common mental disorders and functional limitations influenced
      this risk. A prospective cohort design was established by linking the large
      population based Hordaland Health Study (n > 18000 individuals aged 40-46) with
      an administrative registry on disability pension awards. We modelled hazard
      ratios for later all-cause and diagnosis specific disability pensioning from WSP,
      adjusted for potential confounders and examined the impact of other co-occurring
      health problems and functional limitations. WSP was common (12.4%) and associated
      with a range of mental health, and non-specific and non-musculoskeletal symptoms.
      As expected, WSP was a strong predictor for disability pension award. Hazard
      ratios (HR) adjusted for socio-economic status, health behaviours and comorbid
      medical diagnoses indicated WSP was strongest in predicting pensioning for
      musculoskeletal diagnoses (HR = 5.91, 95% CI 4.64-7.54), but also predicted
      pensioning for mental disorder (HR = 3.13, 95% CI 2.20-4.46) and other diagnoses
      (HR = 1.81, 95% CI 1.30-2.51). Further adjustments for other common symptoms,
      including mental illness, reduced, but did not abolish these risks. WSP is a
      major risk factor for disability pensions, and not only pensions for
      musculoskeletal disorders. The global impact of WSP, and its close association to
      other symptoms, suggests prevention of the severe occupational outcomes for this
      group must have a broad focus and move beyond symptom directed approaches.

PMID- 22396090
TI  - The Over-The-Scope-Clip (OTSC) system is effective in the treatment of chronic
      esophagojejunal anastomotic leakage.
AB  - INTRODUCTION: Management of postoperative esophagojejunal anastomotic leakage
      after total gastrectomy represents a very challenging event. Surgical repair is
      difficult, and conservative treatment can predispose to more severe
      complications. Endoclips and self-expanding stents are useful endoscopic
      therapeutic options but present some drawbacks. The Over-The-Scope-Clip (OTSC)
      system has been shown to be appropriate to close acute small gastrointestinal
      perforations, but its use in the treatment of chronic leakage remains
      controversial. CASE SERIES: The present series reports three consecutive chronic
      esophagojejunal anastomotic leaks successfully treated with OTSC. In all cases,
      clip application was simple, safe and effective, without early and late
      complications. DISCUSSION: The OTSC system may represent a new therapeutic option
      in the management of postoperative esophagojejunal anastomotic leakage.

PMID- 22396091
TI  - Achalasia: pneumatic dilation or laparoscopic heller myotomy?

PMID- 22396094
TI  - The use of bathymetric data in society and science: a review from the Baltic Sea.
AB  - Bathymetry, the underwater topography, is a fundamental property of oceans, seas,
      and lakes. As such it is important for a wide range of applications, like
      physical oceanography, marine geology, geophysics and biology or the
      administration of marine resources. The exact requirements users may have
      regarding bathymetric data are, however, unclear. Here, the results of a
      questionnaire survey and a literature review are presented, concerning the use of
      Baltic Sea bathymetric data in research and for societal needs. It is
      demonstrated that there is a great need for detailed bathymetric data. Despite
      the abundance of high-quality bathymetric data that are produced for safety of
      navigation purposes, the digital bathymetric models publicly available to date
      cannot satisfy this need. Our study shows that DBMs based on data collected for
      safety of navigation could substantially improve the base data for administrative
      decision making as well as the possibilities for marine research in the Baltic
      Sea.

PMID- 22396093
TI  - Phytoremediation potential of aquatic macrophyte, Azolla.
AB  - Aquatic macrophytes play an important role in the structural and functional
      aspects of aquatic ecosystems by altering water movement regimes, providing
      shelter to fish and aquatic invertebrates, serving as a food source, and altering
      water quality by regulating oxygen balance, nutrient cycles, and accumulating
      heavy metals. The ability to hyperaccumulate heavy metals makes them interesting
      research candidates, especially for the treatment of industrial effluents and
      sewage waste water. The use of aquatic macrophytes, such as Azolla with hyper
      accumulating ability is known to be an environmentally friendly option to restore
      polluted aquatic resources. The present review highlights the phytoaccumulation
      potential of macrophytes with emphasis on utilization of Azolla as a promising
      candidate for phytoremediation. The impact of uptake of heavy metals on
      morphology and metabolic processes of Azolla has also been discussed for a better
      understanding and utilization of this symbiotic association in the field of
      phytoremediation.

PMID- 22396095
TI  - Does divergence of nutrient load measurements matter for successful mitigation of
      marine eutrophication?
AB  - Successful implementation of an international nutrient abatement agreement, such
      as the Baltic Sea Action Plan (BSAP), requires consistent understanding of the
      baseline nutrient loads, and a perception of acceptable costs and fairness in
      targeted reductions of these base line loads. This article presents a general
      framework for identifying the implications of divergence between different
      nutrient load quantification approaches, with regard to both cost and fairness
      criteria outcomes, for the international agreement to decrease nutrient loads
      into the Baltic Sea as presented in the BSAP. The results indicate that even
      relatively small divergence in the nutrient load quantification translates into
      relatively large differences in abatement cost for different Baltic Sea
      countries. A robust result, irrespective of differences in nutrient load
      assessments, is a conflict between abatement cost effectiveness and fairness,
      with relatively poor countries facing heavy abatement cost burdens for cost
      effective international load abatement.

PMID- 22396096
TI  - Changes in the chemistry of small Irish lakes.
AB  - A re-survey of acid-sensitive lakes in Ireland (initial survey 1997) was carried
      out during spring 2007 (n = 60). Since 1997, atmospheric emissions of sulfur
      dioxide and deposition of non-marine sulfate (SO(4) (2-)) in Ireland have
      decreased by ~63 and 36%, respectively. Comparison of water chemistry between
      surveys showed significant decreases in the concentration of SO(4) (2-), non
      marine SO(4) (2-), and non-marine base cations. In concert, alkalinity increased
      significantly; however, no change was observed in surface water pH and total
      aluminum. High inter-annual variability in sea salt inputs and increasing (albeit
      non-significant) dissolved organic carbon may have influenced the response of pH
      and total aluminum (as ~70% is organic aluminum). Despite their location on the
      western periphery of Europe, and dominant influence from Atlantic air masses, the
      repeat survey suggests that the chemistry of small Irish lakes has shown a
      significant response to reductions in air pollution driven primarily by the
      implementation of the Gothenburg Protocol under the UNECE Convention on Long
      Range Transboundary Air Pollution.

PMID- 22396097
TI  - Assessment of the Netherlands' flood risk management policy under global change.
AB  - Climate change and sea level rise urge low-lying countries to draft adaption
      policies. In this context, we assessed whether, to what extent and when the
      Netherlands' current flood risk management policy may require a revision. By
      applying scenarios on climate change and socio-economic development and
      performing flood simulations, we established the past and future changes in flood
      probabilities, exposure and consequences until about 2050. We also questioned
      whether the present policy may be extended much longer, applying the concept of
      'policy tipping points'. Climate change was found to cause a significant increase
      of flood risk, but less than economic development does. We also established that
      the current flood risk management policy in the Netherlands can be continued for
      centuries when the sea level rise rate does not exceed 1.5 m per century.
      However, we also conclude that the present policy may not be the most attractive
      strategy, as it has some obvious flaws.

PMID- 22396098
TI  - The influence of traffic noise on vertebrate road crossing through underpasses.
AB  - Noise produces multiple effects on ecosystems and it influences habitat use by
      vertebrates near roads. Thus, it may reduce the effectiveness of mitigation
      measures installed on roads to alleviate population fragmentation. This study
      analyses the effects of noise on the use by vertebrates of 19 underpasses at a
      motorway. It employs generalised linear models to test the effect of three noise
      indicators at the underpasses and in their vicinity on the crossing frequency of
      eight animal species. The results show that the road crossings are subjected to
      high and variable noise levels. Nevertheless, there is no consistent response to
      noise by vertebrates. This suggests that wildlife use of underpasses is
      determined more by habitat characteristics than by the levels of noise tolerated.
      The conclusion is that noise abatement measures on roads in areas of faunal
      sensitivity should focus on general noise reduction rather than on making
      individual crossing places quieter.

PMID- 22396099
TI  - The environmental impact of not having paved roads in arid regions: an example
      from Mongolia.

PMID- 22396100
TI  - Evaluating the impacts of global warming on geomorphological systems.

PMID- 22396101
TI  - Bangladesh needs a "blue-green revolution" to achieve a green economy.

PMID- 22396102
TI  - Mindset change needed for China's water crisis.

PMID- 22396103
TI  - Detecting density dependence in recovering seal population is difficult: a
      response to Svensson et al. (2011).

PMID- 22396104
TI  - The diagnostic value of nipple discharge cytology: breast imaging complements
      predictive value of nipple discharge cytology.
AB  - BACKGROUND: Papilloma is the most common finding associated with pathologic
      nipple discharge. In the absence of breast imaging abnormalities, the incidence
      of occult malignancy is <3%. OBJECTIVE: To determine the predictive value of
      nipple discharge cytology in conjunction with breast imaging. METHODS:
      Retrospective review of 160 charts; inclusion criteria of clinically pathologic
      nipple discharge, subsequent excisional biopsy, and absence of palpable
      abnormalities. Nipple discharge cytology categorized as negative, atypical,
      suspicious, and papillary. Breast imaging was analyzed. Preoperative tests were
      correlated to final surgical pathology. RESULTS: 89 patients identified. Sixty
      five had positive cytology, with a false positive rate of 32.3%. They were
      associated with papillomas in 52%, benign non-papillary in 33% and malignant
      lesions in 9% of cases. Nipple discharge cytology was positive in 69.6% of
      papillomas and 92% of atypical/malignant lesions; 30% had abnormal breast imaging
      and positive cytology. Nipple discharge cytology had a sensitivity of 74.5%,
      specificity of 30%, and positive predictive value of 68%. The positive predictive
      value increased to 85% with associated abnormal breast imaging. CONCLUSIONS:
      Nipple discharge cytology is useful in evaluating pathologic discharge. However,
      negative cytology with negative imaging is not enough to avoid surgery in cases
      of suspicious clinical presentation.

PMID- 22396105
TI  - A Herpesvirus saimiri-based vector expressing TRAIL induces cell death in human
      carcinoma cell lines and multicellular spheroid cultures.
AB  - Herpesvirus saimiri (HVS) is capable of infecting a range of human carcinoma cell
      types with high efficiency and the viral genome persists as high copy number,
      circular, non-integrated episomes which segregate to progeny upon cell division.
      This allows HVS-based vectors to stably transduce a dividing cell population and
      provide sustained transgene expression for an extended period of time both in
      vitro and in vivo. Moreover, the insertion of a bacterial artificial chromosome
      cassette into the HVS genome simplifies the incorporation of large amounts of
      heterologous DNA for gene delivery. Herein we have produced a recombinant HVS
      based vector containing full-length human TRAIL under the control of the alpha
      survivin promoter, and subsequently challenged a variety of cancer cell lines
      with this vector. The TRAIL transgene was expressed in infected colorectal SW480
      cells, causing considerable apoptosis induction. Apoptosis was also observed when
      several other cancer cell lines derived from different tissues were infected.
      Moreover, co-treatment with Jak inhibitor AG490 led to the disruption of spheroid
      cultures grown from the melanoma Mel888 line. These data suggest that an HVS gene
      therapy vector expressing TRAIL could be an effective treatment against cancer.

PMID- 22396106
TI  - Dynamic changes of tyrosine hydroxylase and dopamine concentrations in the
      ventral tegmental area-nucleus accumbens projection during the expression of
      morphine-induced conditioned place preference in rats.
AB  - Our previous study demonstrated that morphine dose- and time-dependently elevated
      dopamine (DA) concentrations in the nucleus accumbens (NAc) during the expression
      of morphine-induced conditioned place preference (CPP) in rats. However, still
      unknown are how DA concentrations dynamically change during the morphine-induced
      CPP test and whether tyrosine hydroxylase (TH) activity in the ventral tegmental
      area (VTA) plays a vital role in this process. In the present study, we measured
      dynamic changes in TH and phosphorylated TH serine 40 (pTH Ser(40)) and pTH
      Ser(31) proteins in the VTA, and DA concentrations in the NAc at 5 min intervals
      during a 30 min morphine-induced CPP test. Rats that underwent morphine-induced
      CPP training significantly preferred the morphine-paired chamber during the CPP
      expression test, an effect that lasted at least 30 min in the drug-free state. DA
      concentrations in the NAc markedly increased at 15 min when the rats were
      returned to the CPP boxes to assess the expression of preference for the
      previously drug-paired chamber. DA concentrations then declined 2 h after the CPP
      test. TH and pTH Ser(40) levels, but not pTH Ser(31) levels, in the VTA were
      enhanced during the CPP test. These results indicated that TH and the
      phosphorylation of TH Ser(40) in the VTA may be responsible for DA synthesis and
      release in the NAc during the behavioral expression of conditioned reward
      elicited by a drug-associated context.

PMID- 22396108
TI  - Tamoxifen-loaded thiolated alginate-albumin nanoparticles as antitumoral drug
      delivery systems.
AB  - Nanoparticles based on disulfide bond reduced bovine serum albumin and thiolated
      alginate (alginate-cysteine conjugate) have been prepared by coacervation method
      and have been loaded with tamoxifen (TMX). The TMX load into the nanoparticles
      was optimized (4-6 MUg/mg NP) by freeze-drying the systems before the loading
      procedure. Maximum TMX release (45-52%) took place between 2 and 25 h.
      Cytotoxicity of unloaded nanoparticles in MCF-7 and HeLa cells was not observed,
      although a small decrease in viability took place at very high concentration.
      Cell uptake of nanoparticles occurred in both cell types and the presence of
      polysaccharide in the nanoparticle composition allowed a better interaction with
      cells. The administration of 10 MUM TMX by TMX-nanoparticles was effective in
      both cellular lines, and the effect of the drug-loaded systems on MCF-7 cell
      cycle showed the efficacy of the TMX-loaded nanoparticles.

PMID- 22396107
TI  - Determination of macrocyclic ellagitannin oenothein B in plant materials by HPLC
      DAD-MS: method development and validation.
AB  - INTRODUCTION: Oenothein B (OeB) is a dimeric macrocyclic ellagitannin occurring
      mainly in the genus Oenothera. In the literature no validated HPLC method for
      quantification of this compound has been reported. OBJECTIVE: To develop and
      validate an efficient HPLC method for quantification of OeB in plant materials.
      METHODOLOGY: Extraction conditions of OeB from plant material were optimised.
      Then the first validated HPLC method for quantification was developed. RESULTS:
      We have shown that ultrasonic-assisted extraction at 40  degrees C in 15 min
      using water are the most optimal conditions for OeB extraction. We have
      quantified OeB in several plant materials belonging to Oenotheraceae family. The
      lowest amount of OeB was present in Circaea lutetiana herb (27.64 +/- 0.26 mg/g)
      and the highest was quantified in Epilobium hirsutum aerial parts (72.91 +/- 1.38
      mg/g). CONCLUSION: The first HPLC method for quantification of OeB in plant
      materials was developed and validated. We also for the first time optimised the
      extraction conditions for OeB.

PMID- 22396109
TI  - Formal alkylation of allenes through highly selective radical cyclizations of
      allene-enes.
AB  - Something radical: the first example of alkene-to-allene radical cyclization of
      allene-enes is reported. The highly chemoselective intermolecular radical
      addition reaction of the alkene and subsequent, exclusive exo-radical addition to
      the allene was realized with perfluoroalkyl radicals. A subsequent TBAF-promoted
      dehydroiodination of the cyclization products forms cyclopentanes and regenerates
      an allene moiety (TBAF=tetra-n-butylammonium fluoride).

PMID- 22396111
TI  - Cutaneous manifestation of Kikuchi-Fujimoto disease in the setting of
      granulomatosis with polyangiitis (Wegener's).

PMID- 22396110
TI  - Guideline-based antibiotics and mortality in healthcare-associated pneumonia.
AB  - BACKGROUND: Guidelines recommend administration of antibiotics with activity
      against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas
      aeruginosa for treatment of healthcare-associated pneumonia (HCAP). It is unclear
      if this therapy improves outcomes for patients with HCAP. OBJECTIVE: To determine
      if administration of guideline-similar therapy (GST) was associated with a
      reduction in 30-day mortality for HCAP. DESIGN: Multi-center retrospective study.
      PARTICIPANTS: Thirteen hundred and eleven admissions for HCAP in six Veterans
      Affairs Medical Centers. INTERVENTIONS: Each admission was classified as
      receiving GST, anti-MRSA or anti-pseudomonal components of GST, or other non-HCAP
      therapy initiated within 48 hours of hospitalization. Association between 30-day
      mortality and GST was estimated with a logistic regression model that included
      GST, propensity to receive GST, probability of recovering an organism from
      culture resistant to antibiotics traditionally used to treat community-acquired
      pneumonia (CAP-resistance), and a GST by CAP-resistance probability interaction.
      MAIN MEASURES: Odds ratios and 95% confidence intervals [OR (95% CI)] of 30-day
      mortality for patients treated with GST and predicted probability of recovering a
      CAP-resistant organism, and ratio of odds ratios [ROR (95% CI)] for treatment by
      CAP-resistance probability interaction. KEY RESULTS: Receipt of GST was
      associated with increased odds of 30-day mortality [OR = 2.11 (1.11, 4.04), P =
      0.02)] as was the predicted probability of recovering a CAP-resistant organism
      [OR = 1.67 (1.26, 2.20), P < 0.001 for a 25% increase in probability]. An
      interaction between predicted probability of recovering a CAP-resistant organism
      and receipt of GST demonstrated lower mortality with GST at high probability of
      CAP resistance [ROR = 0.71(<=1.00) for a 25% increase in probability, P = 0.05].
      CONCLUSIONS: For HCAP patients with high probability of CAP-resistant organisms,
      GST was associated with lower mortality. Consideration of the magnitude of
      patient-specific risk for CAP-resistant organisms should be considered when
      selecting HCAP therapy.

PMID- 22396112
TI  - Resistance of enterobacteria to carbapenem antibiotics is a global crisis.

PMID- 22396113
TI  - Diesel exhausts may expose city dwellers to raised cancer risk.

PMID- 22396114
TI  - Raft of public health services is threatened by health bill, say specialists.

PMID- 22396115
TI  - Physicians call for stronger action on smoking 50 years on from key report.

PMID- 22396116
TI  - Neonatal ward in Bremen is closed down again after two more deaths of babies.

PMID- 22396117
TI  - Neuroscientist is disciplined for falsifying data about effects of alcohol in
      pregnancy.

PMID- 22396118
TI  - Government adviser argues for risk register of NHS changes to be kept private.

PMID- 22396120
TI  - Threatening pictures induce shortened time-to-contact estimates.
AB  - The ability to estimate the time remaining until collision occurs with an
      approaching object (time-to-collision, TTC) is crucial for any mobile animal. In
      the present study, we report three experiments examining whether higher level
      cognitive factors, represented by affective value of approaching objects, could
      affect judgments of TTC. A theory of TTC estimates based purely on the optical
      variable tau does not predict an influence of the affective value of an
      approaching object. In Experiments 1 and 2, we compared TTC estimates of
      threatening and neutral pictures that approached our participants on a screen and
      disappeared from view before a collision would have occurred. Images were taken
      from the International Affective Picture System. Threatening pictures-in
      particular, the picture of a frontal attack-were judged to collide earlier than
      neutral pictures. In Experiment 3, the approaching stimuli were faces with
      different emotional expressions. TTC tended to be underestimated for angry faces.
      We discuss these results, considering the roles of affective and cognitive
      mechanisms modulating TTC estimation and general time perception.

PMID- 22396119
TI  - Enzymatic synthesis of rose aromatic ester (2-phenylethyl acetate) by lipase.
AB  - BACKGROUND: 2-Phenylethyl acetate (2-PEAc) is a highly valued natural volatile
      ester with a rose-like odour that is widely used to add scent or flavour to
      cosmetics, soaps, foods and drinks. In this study, 2-PEAc was synthesised
      enzymatically by transesterification of vinyl acetate with 2-phenethyl alcohol
      catalysed by immobilised lipase (Novozym((r)) 435) from Candida antarctic
      RESULTS: Response surface methodology and a three-level/three-factor Box-Behnken
      design were used to evaluate the effects of time, temperature and enzyme amount
      on the molar conversion % of 2-PEAc. The results showed that temperature was the
      most important variable. Based on the ridge max analysis results, optimum
      enzymatic synthesis conditions were predicted as a reaction time of 79 min, a
      temperature of 57.8  degrees C and an enzyme amount of 122.5 mg. The predicted
      and experimental yields were 86.4 and 85.4% respectively. CONCLUSION: Three
      immobilised lipases were screened and 15 reaction conditions were tested in order
      to find the combination for maximum yield. The optimisation of 2-PEAc synthesis
      catalysed by Novozym((r)) 435 was successfully developed. The kinetic study of
      this transesterification reaction showed that it followed an ordered ping-pong bi
      bi mechanism without any inhibition by reactants.

PMID- 22396121
TI  - Surface characteristics and primary bone marrow stromal cell response of a
      nanostructured strontium-containing oxide layer produced on a microrough titanium
      surface.
AB  - Strontium (Sr) has been successfully used for the treatment of osteoporotic bone,
      increasing new bone formation while reducing bone resorption by stimulating
      proliferation and differentiation of osteoblastic cells and inhibiting osteoclast
      function. In this study, Sr-incorporated Ti oxide layer was produced on
      clinically relevant osteoconductive implant surface, that is, a grit-blasted
      microrough Ti surface, by a simple hydrothermal treatment with the expectation of
      utilizing the osteoblast response enhancement effect of Sr for the future
      applications as a more osteoconductive surface of the permanent load-bearing
      endosseous implants, without altering the original microrough surface features of
      grit-blasted Ti at the micron-scale. This surface exhibits a hierarchical
      structure (i.e., a nanoscale surface architecture of the Sr-incorporated Ti oxide
      layer (SrTiO(3)) imposed on micron-scale rough Ti structure) and Sr ion release
      into physiological solution. In vitro experiments using primary mouse bone marrow
      stromal cells (BMSCs) revealed that the hydrothermally produced SrTiO(3) coating
      promotes both the early and late cell response of BMSCs grown on a microrough Ti
      surface, with notably enhanced attachment, spreading, focal adhesion, alkaline
      phosphatase activity, and expression of critical integrins and osteoblastic
      phenotype genes. These results indicate that a hydrothermally produced SrTiO(3)
      coating improves the osteoconductivity of the microrough Ti surface by enhancing
      both the early and late cell response of BMSCs.

PMID- 22396123
TI  - Bioaccessible nutrients and bioactive components from fortified products prepared
      using finger millet (Eleusine coracana).
AB  - BACKGROUND: Finger millet (Eleusine coracana), a staple food in semi-arid parts
      of the world, is a rich source of nutrients and bioactive components comparable
      to rice and wheat but with higher fibre content. Unprocessed and processed finger
      millet (whole flour (WFM), sieved flour (SFM), wafers and vermicelli with altered
      matrices (added Fe or Zn or reduced fibre)) were analysed for chemical
      composition, bioaccessible Fe, Zn and Ca, in vitro digestible starch (IVSD) and
      protein (IVPD) and bioactive components (polyphenols and flavonoids). RESULTS:
      WFM and SFM flours differed significantly in their composition. Sieving decreased
      the content of both nutrients and antinutrients in WFM but increased their
      digestibility/bioaccessibility. WFM products with Zn and Fe showed highest IVPD,
      whereas SFM products with Fe showed highest IVSD. Products with externally added
      Fe and Zn showed maximum bioaccessibility of Fe and Zn respectively. WFM had the
      highest levels of total polyphenols and flavonoids, 4.18 and 15.85 g kg-1
      respectively; however, bioaccessibility was highest in SFM vermicelli.
      CONCLUSION: The availability of nutrients and bioactive components was influenced
      by both processing methods and compositional alterations of the food matrix in
      finger millet products, and bioaccessibility of all constituents was higher in
      vermicelli (wet matrix) than in wafers (dry matrix).

PMID- 22396122
TI  - The effects of iron oxide incorporation on the chondrogenic potential of three
      human cell types.
AB  - Non-invasive monitoring of living cells in vivo provides an important tool in the
      development of cell-based therapies in cartilage tissue engineering. High
      resolution magnetic resonance imaging (MRI) has been used to monitor target cell
      populations in vivo. However, the side-effects on cell function of the labelling
      reagents, such as superparamagnetic iron oxide (SPIO), are still unclear. This
      study investigated the effect of SPIO particles on the chondrogenic
      differentiation of human bone marrow stromal cells (HBMSCs), neonatal and adult
      chondrocytes in vitro. Cells were labelled with SPIO for 24 h and chondrogenesis
      induced in serum-free medium including TGFbeta3. For labelled/unlabelled cells,
      viability, morphology and proliferation were determined using CellTrackerTM Green
      and PicoGreen dsDNA assays. The expression of SOX9, COL2A1 and ACAN was
      investigated using qRT-PCR after 2, 7 and 14 days. The results showed that
      viability was unaffected in all of the cells but cell morphology changed towards
      a 'stretched' phenotype following SPIO uptake. Cell proliferation was reduced
      only for labelled neonatal chondrocytes. SOX9 and COL2A1 expression decreased at
      day 2 but not at days 7 and 14 for labelled HBMSCs and adult chondrocytes; ACAN
      expression was unaffected. In contrast, SOX9 and COL2A1 expression were
      unaffected in labelled neonatal chondrocytes but a decrease in ACAN expression
      was seen at day 14. The results suggest that downregulation of chondrogenic genes
      associated with SPIO labelling is temporary and target cell-dependent.
      Resovist(r) can be used to label HBMSCs or mature chondrocytes for MR imaging of
      cells for cartilage tissue engineering.

PMID- 22396124
TI  - Optimum yields of dibenzylbutyrolactone-type lignans from Cynareae fruits, during
      their ripening, germination and enzymatic hydrolysis processes, determined by on
      line chromatographic methods.
AB  - INTRODUCTION: Dibenzylbutyrolactone-type lignans are the physiologically active
      constituents of the achene fruits of Cynareae. These lignans occur in
      glycoside/aglycone forms: in the highest quantity of the arctiin/arctigenin,
      matairesinoside/matairesinol and tracheloside/trachelogenin pairs found in the
      fruits of Arctium lappa L., Centaurea scabiosa L. and Cirsium arvense (L.) Scop.
      OBJECTIVE: To optimise the extraction yield of the arctiin/arctigenin,
      matairesinoside/matairesinol and tracheloside/trachelogenin glycoside/aglycone
      pairs, from the fruits of Arctium lappa, Centaurea scabiosa and Cirsium arvense,
      under the ripening, germination and enzymatic hydrolysis processes of the fruits.
      METHODOLOGY: Identification and quantification of lignans were performed with on
      line gas chromatography-mass spectrometry (GC-MS) and with high performance
      liquid chromatography (HPLC), both with UV and mass selective detections (HPLC
      UV/MS). RESULTS: As novelties to the field it was confirmed that: (i) the unripe
      fruits provide a high amount of lignans, similar to the ripe fruit; (ii) the
      fruits of Arctium lappa and Cirsium arvense do have glycosidase activity to
      hydrolyse their lignan glycosides into free lignans; (iii) the glycosidase of
      Centaurea scabiosa fruit becomes activated under its germination process only;
      and (iv) the overwhelming part of the fruits lignan contents (80-94%) in all
      three species are accumulated in the embryo. CONCLUSION: The best sources of (i)
      lignan aglycones are the enzyme-hydrolysed embryos, separating spontaneously
      during the germination process, and (ii) lignan glycosides are the unripe fruits.

PMID- 22396125
TI  - The efficiency of in vitro isolation and myogenic differentiation of MSCs derived
      from adipose connective tissue, bone marrow, and skeletal muscle tissue.
AB  - The objective of the study is to evaluate efficiency of in vitro isolation and
      myogenic differentiation of mesenchymal stem cells (MSCs) derived from adipose
      connective tissue (AD-MSCs), bone marrow (BM-MSCs), and skeletal muscle tissue
      (MC-MSCs). MSCs were isolated from adipose connective tissue, bone marrow, and
      skeletal muscle tissue of two adult 6-wk-old rats. Cultured MSCs were treated
      with 5-azacytidine (AZA) to induce myogenic differentiation. Isolated MSCs and
      differentiated cells were evaluated by immunocytochemistry (ICC), fluorescence
      activated cell sorting (FACS), PCR, and RT-PCR. AD-MSCs showed the highest
      proliferation rate while BM-MSCs had the lowest one. In ICC, isolated MSCs had
      strong CD90- and CD44-positive expression and negative expression of CD45, CD31,
      and CD34, while AZA-treated MSCs had strong positive desmin expression. In FACS
      analysis, AD-MSCs had the highest percentage of CD90- and CD44-positive
      expressing cells (99% and 96%) followed by BM-MSCs (97% and 94%) and MC-MSCs (92%
      and 91%).At 1 wk after incubation with AZA treatment, the peak of myogenin
      expression reached 93% in differentiated MC-MSCs, 83.3% in BM-MSCs, and 77% in AD
      MSCs. MSCs isolated from adipose connective tissue, bone marrow, and skeletal
      muscle tissue have the same morphology and phenotype, but AD-MSCs were the most
      easily accessible and had the highest rate of growth on cultivation and the
      highest percentage of stem cell marker expression. Moreover, although MC-MSCs
      showed the highest rate of myogenic differentiation potential and expression of
      myoblast markers, AD-MSCs and BM-MSCs still can be valuable alternatives. The
      differentiated myoblastic cells could be an available new choice for myoblastic
      auto-transplantation in regeneration medicine.

PMID- 22396126
TI  - Development of an amine dehydrogenase for synthesis of chiral amines.
AB  - A leucine dehydrogenase has been successfully altered through several rounds of
      protein engineering to an enantioselective amine dehydrogenase. Instead of the
      wild-type alpha-keto acid, the new amine dehydrogenase now accepts the analogous
      ketone, methyl isobutyl ketone (MIBK), which corresponds to exchange of the
      carboxy group by a methyl group to produce chiral (R)-1,3-dimethylbutylamine.

PMID- 22396127
TI  - Orthographic similarity: the case of "reversed anagrams".
AB  - How orthographically similar are words such as paws and swap, flow and wolf, or
      live and evil? According to the letter position coding schemes used in models of
      visual word recognition, these reversed anagrams are considered to be less
      similar than words that share letters in the same absolute or relative positions
      (such as home and hose or plan and lane). Therefore, reversed anagrams should not
      produce the standard orthographic similarity effects found using substitution
      neighbors (e.g., home, hose). Simulations using the spatial coding model (Davis,
      Psychological Review 117, 713-758, 2010), for example, predict an inhibitory
      masked-priming effect for substitution neighbor word pairs but a null effect for
      reversed anagrams. Nevertheless, we obtained significant inhibitory priming using
      both stimulus types (Experiment 1). We also demonstrated that robust repetition
      blindness can be obtained for reversed anagrams (Experiment 2). Reversed anagrams
      therefore provide a new test for models of visual word recognition and
      orthographic similarity.

PMID- 22396128
TI  - The consistency of disjunctive assertions.
AB  - In two experiments, we established a new phenomenon in reasoning from
      disjunctions of the grammatical form either A or else B, where A and B are
      clauses. When individuals have to assess whether pairs of assertions can be true
      at the same time, they tend to focus on the truth of each clause of an exclusive
      disjunction (and ignore the concurrent falsity of the other clause). Hence, they
      succumb to illusions of consistency and of inconsistency with pairs consisting of
      a disjunction and a conjunction (Experiment 1), and with simpler problems
      consisting of pairs of disjunctions, such as eIther there is a pie or else there
      is a cake and Either there isn't a pie or else there is a cake (Experiment 2),
      that appear to be consistent with one another, but in fact are not. These results
      corroborate the theory that reasoning depends on envisaging models of
      possibilities.

PMID- 22396129
TI  - Association of human papillomavirus type 31 variants with risk of cervical
      intraepithelial neoplasia grades 2-3.
AB  - Although the lineages of human papillomavirus type 31 (HPV31) variants are
      recognized, their clinical relevance is unknown. The purpose of our study was to
      examine risk of cervical intraepithelial neoplasia Grades 2-3 (CIN2/3) by HPV31
      variants. Study subjects were women who participated in the atypical squamous
      cells of undetermined significance and low-grade squamous intraepithelial lesion
      Triage Study and who had HPV31 infections detected at one or more visits. They
      were followed semi-annually over 2 years for detection of HPV DNA and cervical
      lesion. HPV31 isolates were characterized by DNA sequencing and assigned into 1
      of 3 variant lineages. CIN2/3 was histologically confirmed in 127 (27.0%) of the
      470 HPV31-positive women, 83 diagnosed at the first HPV31-positive visit and 44
      thereafter. The odds ratio for the association of 2-year cumulative risk of
      CIN2/3 was 1.7 (95% CI: 1.0-2.9) for infections with A variants and 2.2 (95% CI:
      1.2-3.9) for infections with B variants as compared to those with C variants.
      Among women without CIN2/3 at the first HPV31-positive visit, the risk of
      subsequent CIN2/3 was 2.2-fold greater for those with A variants (95% CI: 1.0
      4.8) and 2.0-fold greater for those with B variants (95% CI: 0.9-4.9) as compared
      to those with C variants. Similar associations were observed when CIN3 was used
      as the endpoint. The findings from our study help to tag HPV31 variants that
      differ in risk of CIN2/3 and to explain in part why some HPV31 infections regress
      spontaneously and others lead to disease progression.

PMID- 22396131
TI  - A strong bio-inspired layered PNIPAM-clay nanocomposite hydrogel.

PMID- 22396130
TI  - Microwave-sintered 3D printed tricalcium phosphate scaffolds for bone tissue
      engineering.
AB  - This study reports the manufacturing process of 3D interconnected macroporous
      tricalcium phosphate (TCP) scaffolds with controlled internal architecture by
      direct 3D printing (3DP), and high mechanical strength obtained by microwave
      sintering. TCP scaffolds with 27%, 35% and 41% designed macroporosity with pore
      sizes of 500 MUm, 750 MUm and 1000 MUm, respectively, were manufactured by direct
      3DP. These scaffolds were then sintered at 1150  degrees C and 1250  degrees C in
      conventional electric muffle and microwave furnaces, respectively. Total open
      porosity between 42% and 63% was obtained in the sintered scaffolds due to the
      presence of intrinsic micropores along with designed pores. A significant
      increase in compressive strength between 46% and 69% was achieved by microwave
      compared to conventional sintering as a result of efficient densification.
      Maximum compressive strengths of 10.95 +/- 1.28 MPa and 6.62 +/- 0.67 MPa were
      achieved for scaffolds with 500 MUm designed pores (~ 400 MUm after sintering)
      sintered in microwave and conventional furnaces, respectively. An increase in
      cell density with a decrease in macropore size was observed during in vitro cell
      material interactions using human osteoblast cells. Histomorphological analysis
      revealed that the presence of both micro- and macropores facilitated osteoid-like
      new bone formation when tested in femoral defects of Sprague-Dawley rats. Our
      results show that bioresorbable 3D-printed TCP scaffolds have great potential in
      tissue engineering applications for bone tissue repair and regeneration.

PMID- 22396132
TI  - The impact of immobilization of BMP-2 on PDO membrane for bone regeneration.
AB  - Poly(dioxanone) (PDO) is colorless, crystalline, a biodegradable synthetic
      polymers that is used for biomedical applications, such as surgical sutures,
      cardiovascular applications, orthopedics, and plastic surgery. Recently, bone
      morphogenetic protein-2 (BMP-2) is widely used for bone tissue engineering. For
      the first time we report here on the in vitro performance of an electrospun PDO
      membrane immobilized with BMP-2. Immobilized BMP-2 on PDO membrane enhanced
      ALPase activity, the osteogenic differentiation gene expressions as well as cell
      attachment, except cell proliferation when compared to that of PDO membrane
      alone. These results suggest that PDO membrane with BMP-2 is helpful to promote
      bone healing and regeneration.

PMID- 22396133
TI  - Pegvisomant and cabergoline combination therapy in acromegaly.
AB  - Combination with cabergoline may offer additional benefits to acromegalic
      patients on pegvisomant monotherapy. We evaluated the safety and efficacy profile
      of this combination and investigated the determinants of response. An
      observational, retrospective, cross-sectional study. Fourteen acromegalic
      patients (9 females), who were partially resistant to somatostatin analogs and on
      pegvisomant monotherapy. Cabergoline was added because of the presence of
      persistent mildly increased IGF-I. The mean follow-up time was 18.3 +/- 10.4
      months. The efficacy and safety profile was assessed. The influence of clinical
      and biochemical characteristics on treatment efficacy was studied. IGF-I levels
      returned to normal in 4 patients (28%) at the end of the study. In addition, some
      decline in IGF-I levels was observed in a further 5 patients. The % IGF-I
      decreased from 158 +/- 64% to 124 +/- 44% (p = 0.001). The average change in IGF
      I was -18 +/- 27% (range -67 to +24%). Lower baseline IGF-I (p = 0.007), female
      gender (p = 0.013), lower body weight (p = 0.031), and higher prolactin (PRL)
      levels (p = 0.007) were associated with a better response to combination therapy.
      There were no significant severe adverse events. Significant tumour shrinkage was
      observed in 1 patient. Combination therapy with pegvisomant and cabergoline could
      provide better control of IGF-I in some patients with acromegaly. Baseline IGF-I
      levels, female gender, body weight, and PRL levels affect the response to this
      combination therapy.

PMID- 22396134
TI  - Developing evidence-based standards for diagnosis and management of lower urinary
      tract or pelvic floor dysfunction.
AB  - The International Continence Society (ICS) has a key role in standardizing
      terminology related to lower urinary tract and pelvic organ dysfunction. The ICS
      Standardization Steering Committee (SSC) presents the new structure and process
      by which future ICS Standards will be developed. The new processes aim to meet
      present-day evidence-based practice requirements, and to foster unbiased,
      inclusive, and transparent development. For each new ICS Standard, the SSC will
      oversee a dedicated ad hoc Working Group (WG). Applications to chair or
      contribute to a WG will be invited from the ICS membership. The SSC will select
      the Chairperson, and work with him or her to select the WG composition, balanced
      to represent key disciplines, stakeholders, and regions. Consultants can be
      invited to contribute to the WG where specific need arises. Every WG will review
      current knowledge, adhering to evidence-based medicine requirements. Progress
      reports will be reviewed by the SSC, and amendments recommended, culminating in a
      first draft. The draft will be offered to the ICS membership and additional
      relevant experts for comment. Further revision, if needed, will result in a
      document, which the SSC will submit to the ICS Trustees, as arbiters of whether
      the document should be adopted as an ICS Standard. The SCC will then coordinate
      with the WG to ensure that the new ICS Standard is published and disseminated.
      Implementation strategies, such as education, audit, accreditation, and research
      initiatives will be linked to the Standards where appropriate. Revisions of ICS
      Standards will be undertaken to maintain contemporaneous relevance.

PMID- 22396135
TI  - A comparison of two indices for the intraclass correlation coefficient.
AB  - In the present study, we examined the behavior of two indices for measuring the
      intraclass correlation in the one-way random effects model: the prevailing ICC(1)
      (Fisher, 1938) and the corrected eta-squared (Bliese & Halverson, 1998). These
      two procedures differ both in their methods of estimating the variance components
      that define the intraclass correlation coefficient and in their performance of
      bias and mean squared error in the estimation of the intraclass correlation
      coefficient. In contrast with the natural unbiased principle used to construct
      ICC(1), in the present study it was analytically shown that the corrected eta
      squared estimator is identical to the maximum likelihood estimator and the
      pairwise estimator under equal group sizes. Moreover, the empirical results
      obtained from the present Monte Carlo simulation study across various group
      structures revealed the mutual dominance relationship between their truncated
      versions for negative values. The corrected eta-squared estimator performs better
      than the ICC(1) estimator when the underlying population intraclass correlation
      coefficient is small. Conversely, ICC(1) has a clear advantage over the corrected
      eta-squared for medium and large magnitudes of population intraclass correlation
      coefficient. The conceptual description and numerical investigation provide
      guidelines to help researchers choose between the two indices for more accurate
      reliability analysis in multilevel research.

PMID- 22396136
TI  - Adding part-of-speech information to the SUBTLEX-US word frequencies.
AB  - The SUBTLEX-US corpus has been parsed with the CLAWS tagger, so that researchers
      have information about the possible word classes (parts-of-speech, or PoSs) of
      the entries. Five new columns have been added to the SUBTLEX-US word frequency
      list: the dominant (most frequent) PoS for the entry, the frequency of the
      dominant PoS, the frequency of the dominant PoS relative to the entry's total
      frequency, all PoSs observed for the entry, and the respective frequencies of
      these PoSs. Because the current definition of lemma frequency does not seem to
      provide word recognition researchers with useful information (as illustrated by a
      comparison of the lemma frequencies and the word form frequencies from the Corpus
      of Contemporary American English), we have not provided a column with this
      variable. Instead, we hope that the full list of PoS frequencies will help
      researchers to collectively determine which combination of frequencies is the
      most informative.

PMID- 22396137
TI  - Checking and bootstrapping lexical norms by means of word similarity indexes.
AB  - In psychology, lexical norms related to the semantic properties of words, such as
      concreteness and valence, are important research resources. Collecting such norms
      by asking judges to rate the words is very time consuming, which strongly limits
      the number of words that compose them. In the present article, we present a
      technique for estimating lexical norms based on the latent semantic analysis of a
      corpus. The analyses conducted emphasize the technique's effectiveness for
      several semantic dimensions. In addition to the extension of norms, this
      technique can be used to check human ratings to identify words for which the
      rating is very different from the corpus-based estimate.

PMID- 22396138
TI  - The architecture of fibroblast monolayers of different origin differentially
      influences tumor cell growth.
AB  - Normal human and murine fibroblasts can inhibit proliferation of tumor cells when
      co-cultured in vitro. The inhibitory capacity varies depending on the donor and
      the site of origin of the fibroblast. It requires direct cell-to-cell contact and
      is not transferable with supernatant. Here, we show that effective inhibition
      also requires the formation of a morphologically intact fibroblast monolayer
      before the seeding of the tumor cells. Interference with the formation of the
      monolayer impairs the inhibition. Subclones of TERT-immortalized fibroblasts were
      selected on the basis of differences in the growth pattern and related inhibitory
      activity. Whereas the well-organized "whirly" (WH) growth pattern was associated
      with strong inhibition, the disorganized "crossy" (CR) growth pattern was linked
      to reduced inhibition. Time lapse imaging of tumor-fibroblast co-cultures using
      extended field live cell microscopy revealed that fibroblast monolayers with
      growth inhibitory capacity also reduced the motility of the tumor cells whereas
      noninhibitory monolayers had no effect on tumor cell motility. Gene expression
      pattern of two isogenic pairs of fibroblasts, WH and CR subclones of the TERT
      immortalized line (inhibitory, and less inhibitory subsequently) and freshly
      explanted skin (inhibitory) and hernia (noninhibitory) fibroblasts derived from
      the same patient, identified a set of genes that co-segregated with the
      inhibitory phenotype. This suggests that our model system may reveal molecular
      mechanisms involved in contact-mediated microenvironmental surveillance that may
      protect the organism from the outgrowth of disseminated tumor cells.

PMID- 22396139
TI  - Interaction of selected anthocyanins with erythrocytes and liposome membranes.
AB  - Anthocyanins are one of the main flavonoid groups. They are responsible for,
      e.g., the color of plants and have antioxidant features and a wide spectrum of
      medical activity. The subject of the study was the following compounds that
      belong to the anthocyanins and which can be found, e.g., in strawberries and
      chokeberries: callistephin chloride (pelargonidin-3-O-glucoside chloride) and
      ideain chloride (cyanidin-3-O-galactoside chloride). The aim of the study was to
      determine the compounds' antioxidant activity towards the erythrocyte membrane
      and changes incurred by the tested anthocyanins in the lipid phase of the
      erythrocyte membrane, in liposomes composed of erythrocyte lipids and in DPPC,
      DPPC/cholesterol and egg lecithin liposomes. In particular, we studied the effect
      of the two selected anthocyanins on red blood cell morphology, on packing order
      in the lipid hydrophilic phase, on fluidity of the hydrophobic phase, as well as
      on the temperature of phase transition in DPPC and DPPC/cholesterol liposomes.
      Fluorimetry with the Laurdan and Prodan probes indicated increased packing
      density in the hydrophilic phase of the membrane in the presence of anthocyanins.
      Using the fluorescence probes DPH and TMA-DPH, no effect was noted inside the
      hydrophobic phase of the membrane, as the lipid bilayer fluidity was not
      modified. The compounds slightly lowered the phase transition temperature of
      phosphatidylcholine liposomes. The study has shown that both anthocyanins are
      incorporated into the outer region of the erythrocyte membrane, affecting its
      shape and lipid packing order, which is reflected in the increasing number of
      echinocytes. The investigation proved that the compounds penetrate only the outer
      part of the external lipid layer of liposomes composed of erythrocyte lipids,
      DPPC, DPPC/cholesterol and egg lecithin lipids, changing its packing order.
      Fluorimetry studies with DPH-PA proved that the tested anthocyanins are very
      effective antioxidants. The antioxidant activity of the compounds was comparable
      with the activity of Trolox(r).

PMID- 22396140
TI  - Analysis of the role of the integrin signaling pathway in hepatocytes during rat
      liver regeneration.
AB  - To explore the role of the integrin signaling pathway in hepatocytes during rat
      liver regeneration, the integrin signaling pathway-related gene expression
      profile in hepatocytes of regenerative liver was detected using Rat Genome 230
      2.0 array. The chip data showed that 265 genes of the integrin signaling pathway
      were included by Rat Genome 230 2.0 array and 132 genes showed significant
      expression changes in hepatocytes of regenerative liver. The numbers of up-, down
      and up/down-regulated genes were 110, 15 and 7 respectively. In addition,
      bioinformatics and systems biology methods were used to analyze the role of the
      integrin signaling pathway in hepatocytes. The analysis of gene synergy value
      indicated that paths 1, 8, 12, and 15 promoted hepatocyte proliferation at the
      priming phase of liver regeneration; paths 1, 3, 8, and 12-15 enhanced hepatocyte
      proliferation at the progressing phase; paths 11 and 14 promoted hepatocyte
      proliferation, while paths 12 and 13 reduced hepatocyte proliferation at the
      terminal phase. Additionally, the other 8 paths (2, 4, 5-7, 9-10, and 16) were
      not found to be related to liver regeneration. In conclusion, 132 genes and 8
      cascades of the integrin signaling pathway participated in regulating hepatocyte
      proliferation during rat liver regeneration.

PMID- 22396141
TI  - Deficiency in TR4 nuclear receptor abrogates Gadd45a expression and increases
      cytotoxicity induced by ionizing radiation.
AB  - The testicular receptor 4 (TR4) is a member of the nuclear receptor superfamily
      that controls various biological activities. A protective role of TR4 against
      oxidative stress has recently been discovered. We here examined the protective
      role of TR4 against ionizing radiation (IR) and found that small hairpin RNA
      mediated TR4 knockdown cells were highly sensitive to IR-induced cell death. IR
      exposure increased the expression of TR4 in scramble control small hairpin RNA
      expressing cells but not in TR4 knockdown cells. Examination of IR-responsive
      molecules found that the expression of Gadd45a, the growth arrest and DNA damage
      response gene, was dramatically decreased in Tr4 deficient (TR4KO) mice tissues
      and could not respond to IR stimulation in TR4KO mouse embryonic fibroblast
      cells. This TR4 regulation of GADD45A was at the transcriptional level. Promoter
      analysis identified four potential TR4 response elements located in intron 3 and
      exon 4 of the GADD45A gene. Reporter and chromatin immunoprecipitation (ChIP)
      assays provided evidence indicating that TR4 regulated the GADD45A expression
      through TR4 response elements located in intron 3 of the GADD45A gene. Together,
      we find that TR4 is essential in protecting cells from IR stress. Upon IR
      challenges, TR4 expression is increased, thereafter inducing GADD45A through
      transcriptional regulation. As GADD45A is directly involved in the DNA repair
      pathway, this suggests that TR4 senses genotoxic stress and up-regulates GADD45A
      expression to protect cells from IR-induced genotoxicity.

PMID- 22396142
TI  - Expression of cholecystokinin-1 receptor is correlated with proteinuria in human
      diabetic nephropathy.
AB  - This study aimed to examine the expression of cholecystokinin-1 receptor (CCK-1R)
      in the kidneys of type 2 diabetic nephropathy (DN) and the correlation of CCK-1R
      mRNA and proteinuria. Localization of CCK-1R in kidney of diabetic patient with
      nephropathy was examined by immunohistochemistry and in situ hybridization. The
      glomeruli did not express CCK-1R in either control or diabetic nephropathic
      kidneys. However, the expressions of CCK-1R protein and mRNA in tubules were
      significantly increased in DN, which had no relationship with the severity of DN.
      Furthermore, there was a positive correlation between the percentage of cells
      positive for CCK-1R mRNA and the degree of proteinuria. Increased CCK-1R
      expression could be demonstrated in the tubules and the CCK-1R might be
      implicated in the development of proteinuria in human DN.

PMID- 22396144
TI  - Mini-review: pheochromocytomas causing the ectopic ACTH syndrome.
AB  - Cushing's syndrome (CS) is a condition associated with high cortisol levels and
      affects around 0.7-2.4 cases per million population per year [1-3]. Approximately
      80 % of cases of CS are secondary to excess adrenocorticotrophin (ACTH)
      secretion, while in around 20 % the primary abnormality lies in the adrenal, most
      often an adrenal adenoma or carcinoma. Of the ACTH-dependent causes, some 80-90 %
      are due to a pituitary adenoma-Cushing's disease-but in a significant proportion
      the cause is ectopic secretion from a non-pituitary source, the ectopic ACTH
      syndrome (EAS) [4]. The commonest source of ACTH secretion in these patients is a
      bronchial carcinoid. However, many other tumors are capable of secreting ACTH,
      and in most series a small but significant number are secondary to an ACTH
      secreting pheochromocytoma. Amalgamating the data from 6 large series of patients
      with ectopic ACTH, pheochromocytoma was the source of ACTH secretion in 19 out of
      363 patients (5.2 %) [5-11]. In this mini-review, we present a patient presenting
      to our department with a pheochromocytoma as well as Cushing's syndrome due to
      ectopic ACTH secretion by the pheochromocytoma, and we discuss published cases in
      the world literature to assess its significance. We emphasize the problems in the
      simultaneous management of these two serious endocrine conditions.

PMID- 22396143
TI  - Significance of platelet endothelial cell adhesion molecule-1 (PECAM-1) and
      intercellular adhesion molecule-1 (ICAM-1) expressions in preeclamptic placentae.
AB  - Although preeclampsia (PE) is one of the most important problems affecting
      pregnant women, etiologic factors in its development are still unclear. We aimed
      to investigate the expression levels of platelet endothelial cell adhesion
      molecule-1 (PECAM-1) and intercellular adhesion molecule-1 (ICAM-1) in
      preeclamptic and control healthy placentas. Placental tissue samples were
      obtained after delivery from patients diagnosed with PE, and from normal term
      pregnants and analyzed by immunohistochemistry for the expression levels of the
      two adhesion molecules PECAM-1 and ICAM-1. A strong expression of PECAM-1 in
      endothelial cells lining the vessel walls of placental villi in placentas of
      control group was found, but the intensity of PECAM-1 expression was highly
      reduced in placentas of PE group (p = 0.017). Conversely, a strong expression of
      ICAM-1 was observed in placental villi in PE, significantly higher than that of
      normal placentas (p = 0.005). The findings of a decrease of PECAM-1 expression
      and an increase of ICAM-1 expression in preeclamptic placenta suggest the
      existence of functional roles of these adhesion molecules in the pathophysiology
      of PE, probably by contributing to the reduced trophoblast invasion and the
      increased vascular damage, respectively. Inhibiting ICAM-1 (i.e., with ICAM-1
      monoclonal antibody) and promoting PECAM-1 expression may be good therapeutic
      approaches to prevent PE symptoms in the future.

PMID- 22396145
TI  - Observations on the sexual segment of the kidney of snakes with emphasis on
      ultrastructure in the yellow-bellied sea snake, Pelamis platurus.
AB  - The sexual segment of the kidney (SSK) is an accessory sex structure in male
      lizards and snakes (Squamata). We describe histology of the SSK in 12 species of
      snakes, including one from the basal Scolecophidia, Leptotyphlops dulcis, and
      from the more advanced Alethinophidia, species from the Acrochordidae
      (Acrochordus granulatus), Homalopsidae (Cerberus rynchops), Uropeltidae
      (Teretrurus sanguineus), and eight species from the Elapidae, including six
      species of sea snakes. We also describe the ultrastructure of the SSK of the sea
      snake, Pelamis platurus. The SSK of L. dulcis does not include the ureter but
      does include distal convoluted tubules (DCTs) and collecting ducts. In all other
      snakes examined, the SSK is limited to the DCTs and does not differ in histology
      by any consistent character. We found apparently mature individuals of several
      species with inactive SSKs. Hypertrophied SSKs give positive reactions for
      protein secretions but variable reactions for carbohydrates. Ultrastructure of
      the SSK of P. platurus reveals nuclei situated medially in the epithelium and
      mature electron dense secretory vacuoles in other areas of the cytoplasm. Product
      release is apocrine. Junctional complexes only occur at the luminal border, and
      intercellular canaliculi become widened and are open basally. No cytologically
      unique characters occur in the SSK of P. platurus. The ancestral condition of the
      SSK in squamates is the presence of simple columnar epithelium specialized for
      secretion of a protein + carbohydrate product that matures and is released
      seasonally.

PMID- 22396146
TI  - Rhodium/copper-catalyzed annulation of benzimides with internal alkynes: indenone
      synthesis through sequential C-H and C-N cleavage.
AB  - Doubled up: a rhodium(III)/copper(II) system co-catalyzes the annulation of
      benzimides with internal alkynes for the synthesis of indenones (see scheme;
      Cp*=C(5) Me(5)). The reaction involves an uncommon nucleophilic addition of a
      transition-metal-carbon bond to an imide moiety. This novel reaction provides a
      facile route to synthesize indenones from readily available benzimides and
      internal alkynes.

PMID- 22396147
TI  - The effects of defoliation-induced delayed changes in silver birch foliar
      chemistry on gypsy moth fitness, immune response, and resistance to baculovirus
      infection.
AB  - We tested the effects of defoliation-induced changes in silver birch, Betula
      pendula, foliar chemistry (delayed induced resistance, DIR) on the fitness and
      immune defense of the gypsy moth, Lymantria dispar. We measured larval
      developmental time, pupal weight, rate of survival to the adult stage, and five
      characteristics of larval immune defense: (1) encapsulation response; (2)
      phenoloxidase activity; (3) hemocyte concentration and (4) lysozyme-like activity
      in the hemolymph; and (5) resistance to infection by L. dispar
      nucleopolyhedrovirus (LdMNPV). The latter is an entomopathogenic baculovirus that
      often causes epizootics during outbreaks of L. dispar. We also measured the
      involvement of foliage non-tannin phenolic compounds in resistance of B. pendula
      to herbivory as well as the relationship between the compounds we identified and
      L. dispar development, growth, and survival. Leaves of B. pendula with previous
      defoliation history contained increased levels of myricetin glycoside, two
      flavonoid aglycones (acacetin and tetrahydroxy-flavone dimethyl ether), as well
      as one unidentified simple phenolic. The concentrations of two glycosides of
      quercetin, as well as the content of one unidentified flavonoid glycoside were
      significantly decreased under defoliation treatment. DIR of B. pendula retarded
      larval growth rate and increased lysozyme-like activity in the hemolymph, but did
      not affect encapsulation response, phenoloxidase activity, or hemocyte count. We
      did not find any DIR-mediated tritrophic interactions among birch, gypsy moth,
      and LdMNPV. After viral inoculation, the mean hemocyte counts in larvae reared on
      an individual tree correlated significantly with the survival of larvae reared on
      that same tree, indicating that hemocyte density in hemolymph might be associated
      with resistance to viral infection. We found a strong positive correlation
      between the concentration of 1-(4"-hydroxyphenyl)-3'-oxopropyl-beta-D
      glucopyranose and L. dispar survival rate, which may indicate an unlikely role of
      this dominant non-tannin phenolic in B. pendula defense against L. dispar. Our
      study also shows that several immune characteristics of insects that function as
      barriers against different groups of parasites are differently affected by plant
      induced defenses. This underscores the importance of considering multiple factors
      when characterizing barriers to insect immunity.

PMID- 22396149
TI  - Bringing students to the table: the value of student involvement in midwest
      nursing research society.

PMID- 22396148
TI  - Small zebrafish in a big chemical pond.
AB  - The number of possible small organic molecules of different structure is
      virtually limitless. One of the main goals of chemical biologists is to identify,
      from this "chemical space", entities that affect biological processes or systems
      in a specific manner. This can lead to a better understanding of the regulation
      and components of various biological machineries, as well as provide insights
      into efficacious therapeutic targets and drug candidates. However, the challenges
      confronting chemical biologists are multiple. How do we efficiently identify
      compounds that possess desirable activities without unwanted off-target effects?
      Once a candidate compound has been found, how do we determine its mode of action?
      In this Prospects piece, we call attention to recent studies using embryonic and
      larval zebrafish to illustrate the breadth and depth of questions in chemical
      biology that may be addressed using this model, and hope that they can serve as
      catalysts for future investigational ideas.

PMID- 22396150
TI  - Bacterial adhesion on biomedical surfaces covered by micrometric silver Islands.
AB  - A set of Cu-Mn-O and Ag-Cu-Mn-O films were sputter-deposited onto polished Ti-6Al
      4V coupons and the microbiological adherence of Staphylococcus sp. was studied in
      these biomedical surfaces modified by using advanced ternary and quaternary
      oxides, these latter incorporated micrometric silver islands. Silver is known to
      have a natural biocidal character and its presence in the surface of Ti-6Al-4V
      forming large micrometric islands. In principle, predicted to enhance the
      antimicrobial properties of biomedical surfaces. Microbial adhesion tests were
      performed using collection strains and six clinical Staphylococcus aureus and
      Staphylococcus epidermidis strains. The adherence study was performed using a
      previously published protocol by Kinnari et al. Collection strains and clinical
      strains showed decreased adherence to modified materials; however, only on the
      clinical strains were there statistically significant differences between Cu-Mn-O
      and Ag-Cu-Mn-O containing silver islands. Nanocrystalline silver dissolves and
      releases both Ag(+) and Ag(0) whereas other silver sources release only Ag+. We
      can conclude that nanocrystalline silver coating, confirmed by XRD, appears to
      alter the biological properties of the solution, particularly antimicrobial
      activity.

PMID- 22396151
TI  - Differential assembly of polypeptides of the light-harvesting 2 complex encoded
      by distinct operons during acclimation of Rhodobacter sphaeroides to low light
      intensity.
AB  - In order to obtain an improved understanding of the assembly of the bacterial
      photosynthetic apparatus, we have conducted a proteomic analysis of pigment
      protein complexes isolated from the purple bacterium Rhodobacter sphaeroides
      undergoing acclimation to reduced incident light intensity.
      Photoheterotrophically growing cells were shifted from 1,100 to 100 W/m(2) and
      intracytoplasmic membrane (ICM) vesicles isolated over 24-h were subjected to
      clear native polyacrylamide gel electrophoresis. Bands containing the LH2 and
      reaction center (RC)-LH1 complexes were excised and subjected to in-gel trypsin
      digestion followed by liquid chromatography (LC)-mass spectroscopy (MS)/MS. The
      results revealed that the LH2 band contained distinct levels of the LH2-alpha and
      -beta polypeptides encoded by the two puc operons. Polypeptide subunits encoded
      by the puc2AB operon predominated under high light and in the early stages of
      acclimation to low light, while after 24 h, the puc1BAC components were most
      abundant. Surprisingly, the Puc2A polypeptide containing a 251 residue C-terminal
      extension not present in Puc1A, was a protein of major abundance. A predominance
      of Puc2A components in the LH2 complex formed at high light intensity is followed
      by a >2.5-fold enrichment in Puc1B levels between 3 and 24 h of acclimation,
      accompanied by a nearly twofold decrease in Puc2A levels. This indicates that the
      puc1BAC operon is under more stringent light control, thought to reflect
      differences in the puc1 upstream regulatory region. In contrast, elevated levels
      of Puc2 polypeptides were seen 48 h after the gratuitous induction of ICM
      formation at low aeration in the dark, while after 24 h of acclimation to low
      light, an absence of alterations in Puc polypeptide distributions was observed in
      the upper LH2-enriched gel band, despite an approximate twofold increase in
      overall LH2 levels. This is consistent with the origin of this band from a pool
      of LH2 laid down early in development that is distinct from subsequently
      assembled LH2-only domains, forming the LH2 gel band.

PMID- 22396152
TI  - Pesticide use, immunologic conditions, and risk of non-Hodgkin lymphoma in
      Canadian men in six provinces.
AB  - Pesticide exposures and immune suppression have been independently associated
      with the risk of non-Hodgkin lymphoma (NHL), but their joint effect has not been
      well explored. Data from a case-control study of men from six Canadian provinces
      were used to evaluate the potential effect modification of asthma, allergies, or
      asthma and allergies and hay fever combined on NHL risk from use of: (i) any
      pesticide; (ii) any organochlorine insecticide; (iii) any organophosphate
      insecticide; (iv) any phenoxy herbicide; (v) selected individual pesticides [1,1'
      (2,2,2-trichloroethylidene)bis[4-chlorobenzene]; 1,1,1-trichloro-2,2-bis(4
      chlorophenyl) ethane (DDT), malathion, (4-chloro-2-methylphenoxy)acetic acid
      (MCPA), mecoprop, and (2,4-dichlorophenoxy)acetic acid (2,4-D); and (vi) from the
      number of potentially carcinogenic pesticides. Incident NHL cases (n = 513)
      diagnosed between 1991 and 1994 were recruited from provincial cancer registries
      and hospitalization records and compared to 1,506 controls. A stratified analysis
      was conducted to calculate odds ratios (ORs) adjusted for age, province, proxy
      respondent, and diesel oil exposure. Subjects with asthma, allergies, or hay
      fever had non-significantly elevated risks of NHL associated with use of MCPA (OR
      = 2.67, 95% confidence interval [CI]: 0.90-7.93) compared to subjects without any
      of these conditions (OR = 0.81, 95% CI: 0.39-1.70). Conversely, those with
      asthma, allergies, or hay fever who reported use of malathion had lower risks of
      NHL (OR = 1.25, 95% CI: 0.69-2.26) versus subjects with none of these conditions
      (OR = 2.44, 95% CI: 1.65-3.61). Similar effects were observed for asthma and
      allergies evaluated individually. Although there were some leads regarding effect
      modification by these immunologic conditions on the association between pesticide
      use and NHL, small numbers, measurement error and possible recall bias limit
      interpretation of these results.

PMID- 22396154
TI  - Breast cancer and fertility.
AB  - OPINION STATEMENT: The increased availability of assisted reproductive
      technologies (ART) allows women with fertility issues to increase their chances
      of a successful pregnancy with the use of medications that, in some cases,
      increase circulating estrogens. There has been significant concern that the use
      of these medications will increase the risk of hormone-sensitive cancers such as
      breast, ovarian and uterine malignancies. Additionally, for those women who are
      diagnosed with a breast cancer during their reproductive years, this diagnosis
      can be particularly difficult as future fertility is a major concern for many
      young breast cancer survivors. With the current available data, there does not
      appear to be a statistically significant increase in the risk of developing
      breast cancer with ART, although several series suggest a potential possible
      related increase in borderline ovarian and uterine cancers. For breast cancer
      survivors, there does not appear to be an increased risk of death associated with
      subsequent pregnancies when compared with breast cancer patients who did not have
      subsequent pregnancies, although waiting at least 2 years after the diagnosis of
      breast cancer potentially may convey a protective effect. Therefore, when
      systemic therapy for breast cancer is recommended, early counseling and referral
      to a reproductive endocrinologist is warranted to provide optimal fertility
      preservation options. Further safety and outcomes studies are warranted for
      children.

PMID- 22396155
TI  - Trends in cause specific mortality across occupations in Japanese men of working
      age during period of economic stagnation, 1980-2005: retrospective cohort study.
AB  - OBJECTIVE: To assess the temporal trends in occupation specific all causes and
      cause specific mortality in Japan between 1980 and 2005. DESIGN: Longitudinal
      analysis of individual death certificates by last occupation before death. Data
      on population by age and occupation were derived from the population census.
      SETTING: Government records, Japan. PARTICIPANTS: Men aged 30-59. MAIN OUTCOME
      MEASURES: Age standardised mortality rate for all causes, all cancers,
      cerebrovascular disease, ischaemic heart disease, unintentional injuries, and
      suicide. RESULTS: Age standardised mortality rates for all causes and for the
      four leading causes of death (cancers, ischaemic heart disease, cerebrovascular
      disease, and unintentional injuries) steadily decreased from 1980 to 2005 among
      all occupations except for management and professional workers, for whom rates
      began to rise in the late 1990s (P<0.001). During the study period, the mortality
      rate was lowest in other occupations such as production/labour, clerical, and
      sales workers, although overall variability of the age standardised mortality
      rate across occupations widened. The rate for suicide rapidly increased since the
      late 1990s, with the greatest increase being among management and professional
      workers. CONCLUSIONS: Occupational patterns in cause specific mortality changed
      dramatically in Japan during the period of its economic stagnation and resulted
      in the reversal of occupational patterns in mortality that have been well
      established in western countries. A significant negative effect on the health of
      management and professional workers rather than clerks and blue collar workers
      could be because of increased job demands and more stressful work environments
      and could have eliminated or even reversed the health inequality across
      occupations that had existed previously.

PMID- 22396156
TI  - Personal healthcare budgets: what can England learn from the Netherlands?

PMID- 22396157
TI  - Ontogeny of proteolytic signaling and antioxidant capacity in fetal and neonatal
      diaphragm.
AB  - Although upregulation of protein degradation pathways contributes to the
      development of muscle weakness in response to muscle injury and inflammation in
      the adult diaphragm, less is known about the preterm diaphragm. Muscle
      development during the antenatal and early postnatal periods normally results in
      net growth. However, the structural and functional immaturity of the preterm
      diaphragm may predispose it to injury and inflammation induced by adverse
      antenatal and postnatal exposures. Characterization of the ontogeny of diaphragm
      protein degradation pathways in early life is essential to recognize altered
      signaling pathways under pathologic conditions in preterm babies. We assessed the
      relative role of the major proteolytic pathways and antioxidant capacity during
      muscle maturation in ovine fetuses and lambs from 75 days to 200 days
      postconceptual age. Gene expression and protein content of calpain and caspase 3
      exhibited a similar profile with advancing gestation, increasing from 75 days to
      100 days/128 days and subsequently decreasing gradually toward the end of
      gestation. In contrast, ubiquitin conjugating and ligase genes did not change
      during gestation. All proteolytic genes examined (except Ubiquitin) were
      upregulated rapidly after delivery, with a similar developmental trend observed
      in calpain II protein content as well as calpain protease activity. In contrast,
      antioxidant gene expression demonstrated a steady increase from 75 days gestation
      to 24 hr after birth, followed by a significant reduction at 7 weeks of postnatal
      age (P <= 0.002). The proteolytic signaling and antioxidant capacity patterns
      reflect the adaptive process to metabolic change and muscle maturity with
      development.

PMID- 22396158
TI  - Intracellular conformations of human telomeric quadruplexes studied by electron
      paramagnetic resonance spectroscopy.
AB  - In-cell DEER (in-cell double electron electron resonance) is applied to
      investigate quadruplex formation of the human telomeric repeat
      d[AGGG(TTAGGG)(3)]. The initially unfolded DNA sequence forms a mixture of
      different quadruplex topologies upon injection into living cells. In addition,
      time-dependent distance measurements are carried out to monitor quadruplex
      folding.

PMID- 22396160
TI  - Klotho and betaKlotho.
AB  - Endocrine fibroblast growth factors (FGFs) have been recognized as hormones that
      regulate a variety of metabolic processes. FGF19 is secreted from intestine upon
      feeding and acts on liver to suppress bile acid synthesis. FGF21 is secreted from
      liver upon fasting and acts on adipose tissue to promote lipolysis and responses
      to fasting. FGF23 is secreted from bone and acts on kidney to inhibit phosphate
      reabsorption and vitamin D synthesis. One critical feature of endocrine FGFs is
      that they require the Klotho gene family of transmembrane proteins as coreceptors
      to bind their cognate FGF receptors and exert their biological activities. This
      chapter overviews function of Klotho family proteins as obligate coreceptors for
      endocrine FGFs and discusses potential link between Klothos and age-related
      diseases.

PMID- 22396159
TI  - The structural biology of the FGF19 subfamily.
AB  - The ability of the Fibroblast Growth Factor (FGF) 19 subfamily to signal in an
      endocrine fashion sets this subfamily apart from the remaining five FGF
      subfamilies known for their paracrine functions during embryonic development.
      Compared to the members of paracrine FGF subfamiles, the three members of the
      FGF19 subfamily, namely FGF19, FGF21 and FGF23, have poor affinity for heparan
      sulfate (HS) and therefore can diffuse freely in the HS-rich extracellular matrix
      to enter into the bloodstream. In further contrast to paracrine FGFs, FGF19
      subfamily members have unusually poor affinity for their cognate FGF receptors
      (FGFRs) and therefore cannot bind and activate them in a solely HS-dependent
      fashion. As a result, the FGF19 subfamily requires alpha/betaklotho coreceptor
      proteins in order to bind, dimerize and activate their cognate FGFRs. This klotho
      dependency also determines the tissue specificity of endocrine FGFs. Recent
      structural and biochemical studies have begun to shed light onto the molecular
      basis for the klotho-dependent endocrine mode of action of the FGF19 subfamily.
      Crystal structures of FGF19 and FGF23 show that the topology of the HS binding
      site (HBS) of FGF19 subfamily members deviates drastically from the common
      topology adopted by the paracrine FGFs. The distinct topologies of the HBS of
      FGF19 and FGF23 prevent HS from direct hydrogen bonding with the backbone atoms
      of the HBS of these ligands and accordingly decrease the HS binding affinity of
      this subfamily. Recent biochemical data reveal that the ?klotho ectodomain binds
      avidly to the ectodomain of FGFR1c, the main cognate FGFR of FGF23, creating a de
      novo high affinity binding site for the C-terminal tail of FGF23. The isolated
      FGF23 C-terminus can be used to effectively inhibit the formation of the FGF23
      FGFR1c-alphaklotho complex and alleviate hypophosphatemia in renal phosphate
      disorders due to elevated levels of FGF23.

PMID- 22396162
TI  - Evidence for FGF23 involvement in a bone-kidney axis regulating bone
      mineralization and systemic phosphate and vitamin D homeostasis.
AB  - Bone is involved in the maintenance of phosphate and vitamin D homeostasis via
      its production and secretion of FGF23 and serves as a reservoir for the storage
      and release of calcium and phosphate into the circulation. Alterations in
      mineralization of extracellular matrix and the remodeling activities of the
      skeleton are coupled to the kidney conservation of phosphate and production of
      1,25(OH)2D via the regulation of FGF23 production by osteocytes through yet-to-be
      defined locally derived factors. In addition, FGF23 production is regulated by
      1,25(OH)2D in a feedback loop where FGF23 stimulate Cyp24 mediated degradation of
      1,25(OH)2D that serves to protect the organism from the toxic effects of vitamin
      D excess. In this chapter, we will review the regulation and function of FGF23.

PMID- 22396163
TI  - FGF23, klotho and vitamin D interactions: What have we learned from in vivo mouse
      genetics studies?
AB  - The molecular interactions of fibroblast growth factor 23 (FGF23), klotho and
      vitamin D coordinate to regulate the delicate phosphate levels of the body.
      Vitamin D can induce both FGF23 and klotho synthesis to influence renal phosphate
      balance. In the presence of klotho, FGF23 protein gains bioactivity to influence
      systemic phosphate homeostasis. Experimental studies have convincingly shown that
      in the absence of klotho, FGF23 is unable to regulate in vivo phosphate
      homeostasis. Furthermore, genetic inactivation of FGF23, klotho or both of the
      genes have resulted in markedly increased renal expression of 1-alpha hydroxylase
      [1alpha(OH)ase] and concomitant elevated serum levels of 1,25, dihydroxyvitamin D
      [1,25(OH)(2)D] in the mutant mice. Vitamin D can induce the expression of both
      FGF23 and klotho while, FGF23 can suppress renal expression of 1alpha(OH)ase to
      reduce 1,25(OH)(2)D activity. In this brief chapter, I will summarize the
      possible in vivo interactions of FGF23, klotho and vitamin D, in the light of
      recent mouse genetics studies.

PMID- 22396164
TI  - FGF23 and the parathyroid.
AB  - Klotho and fibroblast growth factor 1 (FGFR1) are expressed not only in FGF23's
      classical target organ, the kidney, but also in other organs such as the
      parathyroid. FGF23 acts on the parathyroid to decrease PTH mRNA and serum PTH
      levels. It does this by activating the MAPK pathway. In chronic kidney disease
      there are very high levels of serum FGF23 together with increased serum PTH
      levels, implying resistance of the parathyroid to the action of FGF23. This has
      been shown in parathyroid tissue surgically removed from dialysis patients as
      well as in experimental models of uremia to be due to down-regulation of klotho
      FGFR1 expression in the parathyroid. Moreover, the parathyroids of rats with
      advanced uremia do not respond to administered FGF23 by activation of the MAPK
      pathway or inhibition of PTH secretion. Therefore, there is down-regulation of
      parathyroid klotho-FGFR1 in CKD which correlates with the resistance of the
      parathyroid to FGF23. A further subject of great interest in this field is the
      effect of PTH to directly increase FGF23 expression by osteoblast like cells in
      culture and the observations that parathyroidectomy prevents and corrects the
      increased serum FGF23 level of experimental CKD as well as decreases FGF23 in
      patients with CKD. There is therefore a negative feedback loop between bone and
      the parathyroid.

PMID- 22396165
TI  - Regulation of ion channels by secreted Klotho.
AB  - Klotho is an anti-aging protein predominantly expressed in the kidney,
      parathyroid glands and choroid plexus of the brain. Klotho exists in two forms, a
      membrane form and a soluble secreted form. Recent studies show that the secreted
      Klotho possess sialidase activity and regulates several ion channels via the
      activity. Removal of terminal sialic acids from N-glycan chains of the epithelial
      Ca(2+) channel TRPV5 and the renal K(+) channel ROMK by secreted Klotho exposes
      the underlying disaccharide galactose-N-acetylglucosamine, a ligand for galectin
      1. Binding to galectin-1 at the extracellular surface prevents internalization
      and leads to accumulation of the channels on the plasma membrane. Future studies
      will investigate whether secreted Klotho regulates cell-surface expression of
      other membrane glycoproteins via the same mechanism.

PMID- 22396161
TI  - FGF23 and syndromes of abnormal renal phosphate handling.
AB  - Fibroblast growth factor 23 (FGF23) is part of a previously unrecognized hormonal
      bone-parathyroid-kidney axis, which is modulated by 1,25(OH)(2)-vitamin D
      (1,25(OH)(2)D), dietary and circulating phosphate and possibly PTH. FGF23 was
      discovered as the humoral factor in tumors that causes hypophosphatemia and
      osteomalacia and through the identification of a mutant form of FGF23 that leads
      to autosomal dominant hypophosphatemic rickets (ADHR), a rare genetic disorder.
      FGF23 appears to be mainly secreted by osteocytes where its expression is up
      regulated by 1,25(OH)(2)D and probably by increased serum phosphate levels. Its
      synthesis and secretion is reduced through yet unknown mechanisms that involve
      the phosphate-regulating gene with homologies to endopeptidases on the X
      chromosome (PHEX), dentin matrix protein 1 (DMP1) and ecto-nucleotide
      pyrophosphatase/phosphodiesterase 1 (ENPP1). Consequently, loss-of-function
      mutations in these genes underlie hypophosphatemic disorders that are either X
      linked or autosomal recessive. Impaired O-glycosylation of FGF23 due to the lack
      of UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyl
      transferase 3 (GALNT3) or due to certain homozygous FGF23 mutations results in
      reduced secretion of intact FGF23 and leads to familial hyperphosphatemic tumoral
      calcinosis. FGF23 acts through FGF-receptors and the coreceptor Klotho to reduce
      1,25(OH)(2)D synthesis in the kidney and probably the synthesis of parathyroid
      hormone (PTH) by the parathyroid glands. It furthermore synergizes with PTH to
      increase renal phosphate excretion by reducing expression of the sodium-phosphate
      cotransporters NaPi-IIa and NaPi-IIc in the proximal tubules. Loss-of-function
      mutations in these two transporters lead to autosomal recessive Fanconi syndrome
      or to hereditary hypophosphatemic rickets with hypercalciuria, respectively.

PMID- 22396166
TI  - FGF23 in chronic kidney disease.
AB  - Chronic kidney disease (CKD) is a growing public health epidemic that is
      associated with a markedly increased risk of cardiovascular mortality. Disordered
      mineral metabolism and particularly, disordered phosphorus metabolism appears to
      be a contributing factor. Fibroblast growth factor 23 (FGF23) regulates
      phosphorus and vitamin D metabolism. Its levels increase progressively beginning
      in early CKD, presumably as a physiological adaptation to maintain normal serum
      phosphate levels or normal phosphorus balance. FGF23 promotes phosphaturia and
      decreases production of calcitriol. Recent studies suggest that increased FGF23
      is associated with mortality, left ventricular hypertrophy, endothelial
      dysfunction and progression of CKD. These results were consistently independent
      of serum phosphate levels. At the very least, FGF23 is emerging as a novel
      biomarker that may help identify which CKD patients might benefit most from
      aggressive management of disordered phosphorus metabolism. It is also possible
      that markedly increased FGF23 levels in CKD could contribute directly to tissue
      injury in the heart, vessels and kidneys, an exciting question that is sure to be
      the topic of intense investigation in the near future.

PMID- 22396168
TI  - FGF23 as a novel therapeutic target.
AB  - Fibroblast growth factor (FGF) 23 is a hormone that acts to decrease phosphate,
      1,25-dihydroxyvitamin D and parathyroid hormone levels in circulation.
      Particularly, appropriate actions of FGF23 are essential for maintaining
      physiological phosphate and vitamin D metabolism. Therefore, either gain or loss
      of function of FGF23 can impair these homeostatic regulations, causing several
      metabolic bone diseases. The measurement of circulating levels of FGF23 in
      patients with various types of hypophosphatemic rickets and/or osteomalacia has
      revealed that several of them are FGF23-dependent diseases, highlighting a novel
      therapeutic concept that the inhibition of the excess activity of FGF23 could be
      beneficial for patients with these diseases. Indeed, preliminary studies with a
      mouse disease model have validated this concept. On the other hand, replacement
      therapy with recombinant FGF23 may be applied to the disease caused by loss of
      function of FGF23. Although these concepts still need to be proven with more
      detailed analyses, the latest knowledge on the FGF23-related diseases and the
      development of methods to appropriately regulate FGF23 actions may
      synergistically create novel therapeutic maneuvers.

PMID- 22396169
TI  - Physiology of FGF15/19.
AB  - This chapter will review the various biological actions of the mouse fibroblast
      growth factor 15 (Fgf15) and human fibroblast growth factor 19 (FGF19). Unlike
      other members of the fibroblast growth factor (FGF) family, the Fgf15 and FGF19
      orthologs do not share a high degree of sequence identity. Fgf15 and FGF19 are
      members of an atypical subfamily of FGFs that function as hormones. Due to subtle
      changes in tertiary structure, these FGFs have low heparin binding affinity
      enabling them to diffuse away from their site of secretion and signal to distant
      cells. FGF signaling through the FGF receptors is also different for this sub
      family, requiring klotho protein cofactors rather than heparin sulfate
      proteoglycan. Mouse Fgf15 and human FGF19 play key roles in enterohepatic
      signaling, regulation of liver bile acid biosynthesis, gallbladder motility and
      metabolic homeostasis.

PMID- 22396170
TI  - FGF19 and cancer.
AB  - Fibroblast growth factors (FGFs) and their cognate receptors, FGF receptors
      (FGFRs), play critical roles in a variety of normal developmental and
      physiological processes. Numerous reports support a role for deregulation of FGF
      FGFR signaling, whether it is at the ligand and/or receptor level, in tumor
      development and progression. The FGF19-FGFR4 signaling axis has been implicated
      in the pathogenesis of several cancers, including hepatocellular carcinomas in
      mice and potentially in humans. This chapter focuses on recent progress in the
      understanding of the molecular mechanisms of FGF19 action and its potential
      involvement in cancer.

PMID- 22396171
TI  - Understanding the structure-function relationship between FGF19 and its mitogenic
      and metabolic activities.
AB  - FGF19 differs from the classical FGFs in that it has a much-reduced heparan
      sulfate proteoglycan binding affinity that allows it to act as endocrine hormone.
      Although FGF19 regulates several different metabolic activities, it still
      activates downstream signaling pathways through FGF receptors, in a similar
      manner to that seen in classical FGFs. Aberrant FGF signaling has been implicated
      in tumor development, and mouse models have confirmed that FGF19 has the
      potential to induce hepatocellular carcinoma. Treatment with anti-FGF19 antibody
      suppressed tumor progression in both FGF19 transgenic mice and colon cancer cell
      xenograft models. FGFR4, the predominant FGF receptor expressed in the liver, may
      play an important role in FGF19-mediated tumorigenesis. This review reports the
      current advances in understanding the structure-function relationship between
      FGF19 and its interactions with FGFRs, its physiological activities, and its
      differences from FGF21. The review also discusses strategies to separate the
      mitogenic and metabolic activities for the development of potential therapeutic
      molecules based on FGF19.

PMID- 22396167
TI  - Secreted klotho and chronic kidney disease.
AB  - Soluble Klotho (sKl) in the circulation can be generated directly by alterative
      splicing of the Klotho transcript or the extracellular domain of membrane Klotho
      can be released from membrane-anchored Klotho on the cell surface. Unlike
      membrane Klotho which functions as a coreceptor for fibroblast growth factor-23
      (FGF23), sKl, acts as hormonal factor and plays important roles in anti-aging,
      anti-oxidation, modulation of ion transport, and Wnt signaling. Emerging evidence
      reveals that Klotho deficiency is an early biomarker for chronic kidney diseases
      as well as a pathogenic factor. Klotho deficiency is associated with progression
      and chronic complications in chronic kidney disease including vascular
      calcification, cardiac hypertrophy, and secondary hyperparathyroidism. In
      multiple experimental models, replacement of sKl, or manipulated up-regulation of
      endogenous Klotho protect the kidney from renal insults, preserve kidney
      function, and suppress renal fibrosis, in chronic kidney disease. Klotho is a
      highly promising candidate on the horizon as an early biomarker, and as a novel
      therapeutic agent for chronic kidney disease.

PMID- 22396172
TI  - FGF21 as a therapeutic reagent.
AB  - The prevalence of obesity and diabetes has been dramatically increasing during
      the last decade suggesting a greater patient need for more efficacious and safer
      drugs. Large molecule therapy has played an important role in diabetes since the
      discovery of insulin. This legacy was continued upon the introduction of Humulin
      (first recombinant insulin), Humalog (first engineered insulin) and Byetta (first
      incretin mimetic). Several other protein therapeutics, such as leptin,
      adiponectin, bone morphogenic protein-9 and others, are currently in or
      considered for therapeutic development. Among them, FGF21 is one of the most
      promising candidates given its outstanding pharmacologic benefits for nearly each
      and every abnormality of a metabolic disease and lack of apparent side effects in
      a variety of animal models. Thus, FGF21 represents a novel and appealing
      therapeutic reagent for Type 2 diabetes mellitus, obesity, dyslipidemia,
      cardiovascular and fatty liver diseases. The in vitro biology, genetic animal
      models and in vivo pharmacology of FGF21 will be discussed in this chapter.

PMID- 22396173
TI  - Comparative genomic structures of Mycobacterium CRISPR-Cas.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) are
      inheritable genetic elements of many archaea and bacteria, conferring acquired
      immunity against invading nucleic acids. CRISPR might be indicative of the
      bacterial niche adaptation and evolutionary. Mycobacterium is an important genus
      occupying diverse niches with profound medical and environmental significance. To
      present a comparative genomic landscape of the Mycobacterium CRISPR, the feature
      of mycobacterium CRISPR structures with sequenced complete genomes were
      bioinformatically analyzed. The results show that CRISPR structures can be found
      among 14 mycobacteria, and all loci are chromosomally located. Long CRISPRs
      present in three species, namely M. tuberculosis, M. bovis, and M. avium.
      Integrated CRISPR-Cas system can only be found in M. tuberculosis and M. bovis,
      with highly conserved repeat sequences, very short leaders, and promoterless. M.
      tuberculosis and M. bovis repeat sequences cannot form stable RNA secondary
      structure, consistent with a Cas6-binding sequence. M. avium repeat sequences can
      form classical stem-loop structure. A three-step model of M. tuberculosis CRISPR
      Cas system action was put forward based on the composition and function of cas
      genes cluster. M. tuberculosis and M. bovis CRISPRs might interfere with the
      invading nucleic acids, but have somehow lost the capacity to incorporate new
      spacers and co-evolve with corresponding mycobacteriophages.

PMID- 22396174
TI  - Pathological gambling, problem gambling and sleep complaints: an analysis of the
      National Comorbidity Survey: Replication (NCS-R).
AB  - The purpose of this study is to investigate the relationship between sleep
      disturbances and gambling behavior. Data from the National Comorbidity Survey
      Replication (NCS-R) was used to examine the relationship between three specific
      sleep complaints (difficulty initiating sleep [DIS], difficulty maintaining sleep
      [DMS], and early morning awakening [EMA]) and gambling behavior. Bivariate
      logistic regression models were used to control for potentially confounding
      psychiatric disorders and age. Almost half of respondents with problem gambling
      behavior (45.9%) and two thirds (67.7%) of respondents with pathological gambling
      behavior reported at least one sleep compliant. Compared to respondents with no
      gambling pathology, respondents with pathological gambling were significantly
      more likely to report at least one sleep complaint (Adjusted Odds Ratio [AOR] =
      3.444, 95% CI = 1.538-7.713), to report all sleep complaints (AOR = 3.449, 95% CI
      = 1.503-7.914), and to report any individual complaint (DIS: OR = 2.300, 95% CI =
      1.069-4.946; DMS: AOR = 4.604, 95% CI = 2.093-10.129; EMA: AOR = 3.968, 95% CI =
      1.856-8.481). The relationship between problem gambling and sleep complaints were
      more modest (any sleep complaint: AOR = 1.794, 95% CI = 1.142-2.818; all three
      sleep complaints: AOR = 2.144, 95% CI = 1.169-3.931; DIS: AOR = 1.961, 95% CI =
      1.204-3.194; DMS: AOR = 1.551, 95% CI = 0.951-2.529; EMA: AOR = 1.796, 95% CI =
      1.099-2.935). Given the individual and societal ramifications linked with the
      presence of sleep problems, this study presents another health-related
      repercussion associated with gambling pathology rarely discussed in the
      literature.

PMID- 22396178
TI  - Implementing clinical practice guidelines: a responsibility for nurses and allied
      health professionals?

PMID- 22396176
TI  - A semiempirical approach to ligand-binding affinities: dependence on the
      Hamiltonian and corrections.
AB  - We present a combination of semiempirical quantum-mechanical (SQM) calculations
      in the conductor-like screening model with the MM/GBSA (molecular-mechanics with
      generalized Born and surface-area solvation) method for ligand-binding affinity
      calculations. We test three SQM Hamiltonians, AM1, RM1, and PM6, as well as
      hydrogen-bond corrections and two different dispersion corrections. As test
      cases, we use the binding of seven biotin analogues to avidin, nine inhibitors to
      factor Xa, and nine phenol-derivatives to ferritin. The results vary somewhat for
      the three test cases, but a dispersion correction is mandatory to reproduce
      experimental estimates. On average, AM1 with the DH2 hydrogen-bond and dispersion
      corrections gives the best results, which are similar to those of standard
      MM/GBSA calculations for the same systems. The total time consumption is only 1.3
      1.6 times larger than for MM/GBSA.

PMID- 22396179
TI  - Validity and reliability of the German version of the 9-item European Heart
      Failure Self-care Behaviour Scale.
AB  - BACKGROUND: The promotion of self-care in patients with heart failure (HF) is a
      promising strategy for maintaining health and preventing exacerbation of HF and a
      continuous need for healthcare services. To assess patient self-care, valid and
      reliable instruments are needed, but there is no psychometrically tested
      instrument for use in a German HF population. AIM: The aim of this study was to
      determine the validity and reliability of the German version of the 9-item
      European Heart Failure Self-care Behaviour Scale (G9-EHFScBS). Construct validity
      including factor analysis and discriminant validity, concurrent validity, test
      retest reliability and internal consistency were analysed. METHODS AND RESULTS:
      The G9-EHFScBS was translated into German, and its validity and reliability were
      tested with 109 patients. The item-total correlation ranged from 0.09 to 0.63.
      Internal consistency was fair, with a Cronbach's alpha of 0.71 (95%CI: 0.63 to
      0.77). Test-retest reliability using an intra-class correlation coefficient
      showed substantial agreement for the entire scale (ICC: 0.69; 95%CI: 0.56 to
      0.79). The G9-EHFScBS was able to distinguish patients with and without extra HF
      education at a statistically significant level (t = 2.105; p = 0.04). A factor
      analysis did not show the theoretical assumed dimensions of the scale.
      CONCLUSION: The G9-EHFScBS is deemed a valid and reliable instrument to assess HF
      specific self-care in a German HF population.

PMID- 22396180
TI  - Fast diffusion tensor imaging and tractography of the whole cervical spinal cord
      using point spread function corrected echo planar imaging.
AB  - Diffusion tensor imaging has been used in a number of spinal cord studies, but
      severe distortions caused by susceptibility induced field inhomogeneities limit
      its applicability to investigate small volumes within acceptable acquisition
      times. A way to evaluate image distortions is to map the point spread function of
      the voxel intensity in a reference scan. In this study, the point spread function
      was mapped for an echo-planar imaging sequence in the human cervical spinal cord
      with isotropic resolution and large field of view. Correction with the point
      spread function map improved anatomical consistency, and full cervical
      tractography was thereby possible from a C1 seed region in healthy controls and
      one individual with spinal cord injury. It is suggested that point spread
      function mapping of the spinal cord can be used in combination with sequence
      based methods for reduction of susceptibility artifacts or in high-field imaging
      settings where off-resonance effects are pronounced.

PMID- 22396175
TI  - End-point effector stress mediators in neuroimmune interactions: their role in
      immune system homeostasis and autoimmune pathology.
AB  - Much evidence has identified a direct anatomical and functional link between the
      brain and the immune system, with glucocorticoids (GCs), catecholamines (CAs),
      and neuropeptide Y (NPY) as its end-point mediators. This suggests the important
      role of these mediators in immune system homeostasis and the pathogenesis of
      inflammatory autoimmune diseases. However, although it is clear that these
      mediators can modulate lymphocyte maturation and the activity of distinct immune
      cell types, their putative role in the pathogenesis of autoimmune disease is not
      yet completely understood. We have contributed to this field by discovering the
      influence of CAs and GCs on fine-tuning thymocyte negative selection and, in
      particular, by pointing to the putative CA-mediated mechanisms underlying this
      influence. Furthermore, we have shown that CAs are implicated in the regulation
      of regulatory T-cell development in the thymus. Moreover, our investigations
      related to macrophage biology emphasize the complex interaction between GCs, CAs
      and NPY in the modulation of macrophage functions and their putative significance
      for the pathogenesis of autoimmune inflammatory diseases.

PMID- 22396181
TI  - Development of a short form of the Brazilian Parental-Caregiver Perceptions
      Questionnaire using exploratory and confirmatory factor analysis.
AB  - PURPOSE: This study presents the Brazilian short form of the P-CPQ. METHODS: Data
      from a representative sample of 702 parents/caregivers of children were randomly
      divided in two subsamples. A development sample (n = 502) was used for
      exploratory factor analysis (EFA), and a validation sample (n = 200) was used for
      confirmatory factor analysis (CFA). The EFA was used to determine the
      hypothetical factor structure and internal consistency. The CFA was applied to
      test the factor structure of the original P-CPQ, alternative models and the
      validity and reliability of the Brazilian short form of the P-CPQ. RESULTS: A 3
      factor model (alternative model 2) had a factor structure with high factor
      loadings, acceptable fit indices (chi(2)/df = 2.38; GFI = 0.90; CFI = 0.90; TLI =
      0.87; AGFI = 0.85; SRMR = 0.07) and both convergent and discriminant validity
      (Pearson bivariate zero order correlations among factors <0.85). CONCLUSIONS: The
      Brazilian P-CPQ with three subscales and 13 items appears to be a valid short
      version to be used in further studies to evaluate parents/caregivers' perceptions
      of children's oral health-related quality of life.

PMID- 22396182
TI  - Sleep apnoea attenuates the effects of a lifestyle intervention programme in men
      with visceral obesity.
AB  - BACKGROUND: Excess visceral adiposity and sleep apnoea are two conditions
      independently associated with cardiovascular diseases. The two conditions are
      often combined and are believed to interact in a vicious circle. OBJECTIVES: To
      compare the response of men with visceral obesity with or without sleep apnoea
      syndrome to a 1-year healthy eating, physical activity/exercise intervention
      programme. METHODS: 77 men, selected on the basis of increased waist
      circumference (>=90 cm) and dyslipidaemia (triglycerides >=1.69 and/or high
      density lipoprotein (HDL) cholesterol <1.03 mmol/litre), participated in this
      study. Body composition and fat distribution were assessed by dual-emission X-ray
      absorptiometry or CT and sleep breathing disorders by home-based polygraphic
      recording. Cardiorespiratory fitness, plasma adipokines, plasma inflammatory
      markers, fasting lipoprotein-lipid profile and oral glucose tolerance test were
      assessed. RESULTS: After the 1-year lifestyle intervention, the mean oxygen
      desaturation index (ODI) of the whole sample decreased (-3+/-13 events/h,
      p<0.05). Men with sleep apnoea syndrome at baseline (ODI >=10 events/h, n=28)
      showed smaller reductions in body mass index, waist circumference, triglycerides
      and smaller increases in HDL cholesterol and adiponectin than men without sleep
      apnoea (ODI <10 events/h, n=49), despite similar compliance to the programme. The
      higher the baseline ODI and the time spent under 90% saturation, the lower the
      reductions in fat mass and visceral adiposity, and the smaller the improvement in
      glucose/insulin homeostasis indices after 1 year. CONCLUSIONS: Men with sleep
      apnoea syndrome at baseline had smaller reduction in body weight and less
      metabolic improvements associated with the lifestyle intervention programme than
      men without sleep apnoea syndrome.

PMID- 22396183
TI  - Surveillance and survival among adolescents and young adults with cancer in
      Ontario, Canada.
AB  - Gains in survival rates among adolescents and young adults (AYA) are reported
      from the USA to be lower than in both younger and older patients. Limiting
      factors include low accrual to clinical trials related to the type of
      institutional care. This study aimed to determine the incidence of cancer in the
      15-29 age group in Ontario, and the 5-year survival of these cases by disease
      class, age at diagnosis group and highest level of institutional complexity of
      care. The primary data source was Cancer Care Ontario (CCO). Diseases were
      classified according to an AYA-specific system. Age at diagnosis was grouped as
      15-19, 20-24 and 25-29 years; and institutional site of care was categorized as
      pediatric oncology group of Ontario (POGO) centers, regional cancer centers (RCC
      tertiary care centers associated with CCO), RCC affiliate and satellite
      institutions and other institutions having no specialized cancer services. More
      than 10,000 incident cases were identified during 1990-2001. Carcinomas and
      lymphomas each accounted for > 20% of the total. Overall 5-year survival rate was
      83%; significantly higher for lymphomas at POGO centers and RCC than elsewhere.
      About 40% of eligible AYA cases were treated at a POGO center and 25% of those
      were accrued to clinical trials. The low proportion of adolescents referred to
      pediatric cancer centers may result in a survival disadvantage for this group.
      All AYA, especially with lymphomas, should be referred to specialized centers.
      Accrual of AYA to clinical trials must be improved substantially.

PMID- 22396184
TI  - Robotic totally endoscopic coronary artery bypass grafting for spontaneous
      coronary artery dissection.
AB  - BACKGROUND: Patients with spontaneous coronary artery dissection may require
      surgical revascularization. Reports on the surgical management of this pathology
      are primarily limited to classic coronary artery bypass grafting via sternotomy
      on cardiopulmonary bypass, although a limited number of reports of alternatives
      also exist. METHODS: We describe a case of robotic completely endoscopic coronary
      surgery using the daVinci(r) SiTM system in a patient with spontaneous coronary
      artery dissection. RESULTS: Robotically assisted single left internal mammary
      artery grafting to the left coronary artery system was carried out successfully
      in a completely endoscopic fashion. CONCLUSIONS: Selected patients with
      spontaneous coronary artery dissection may benefit from a totally endoscopic
      approach to surgical coronary revascularization.

PMID- 22396186
TI  - [Interfere with contract physician's fee schedules? YES!].

PMID- 22396185
TI  - Reversal effects of pantoprazole on multidrug resistance in human gastric
      adenocarcinoma cells by down-regulating the V-ATPases/mTOR/HIF-1alpha/P-gp and
      MRP1 signaling pathway in vitro and in vivo.
AB  - To investigate reversal effects of pantoprazole (PPZ) on multidrug resistance
      (MDR) in human gastric adenocarcinoma cells in vivo and in vitro. Human gastric
      adenocarcinoma cell SGC7901 was cultured in RPMI-1640 medium supplemented with
      10% fetal bovine serum and antibiotics in a humidified 5% CO(2) atmosphere at 37
      degrees C. Adriamycin (ADR)-resistant cells were cultured with addition of 0.8
      ug/ml of ADR maintaining MDR phenotype. ADR was used to calculate ADR releasing
      index; CCK-8 Assay was performed to evaluate the cytotoxicity of anti-tumor
      drugs; BCECF-AM pH-sensitive fluorescent probe was used to measure intracellular
      pH (pHi) value of cells, whereas pH value of medium was considered as
      extracellular pH (pHe) value; Western blotting and immunofluorescent staining
      analyses were employed to determine protein expressions and intracellular
      distributions of vacuolar H(+) -ATPases (V-ATPases), mTOR, HIF-1alpha, P
      glycoprotein (P-gp), and multidrug resistant protein 1 (MRP1); SGC7901 and
      SGC7901/ADR cells were inoculated in athymic nude mice. Thereafter, effects of
      ADR with or without PPZ pretreatment were compared by determining the tumor size
      and weight, apoptotic cells in tumor tissues were detected by TUNEL assay. At
      concentrations greater than 20 ug/ml, PPZ pretreatment reduced ADR releasing
      index and significantly enhanced intracellular ADR concentration of SGC7901 (P <
      0.01). Similarly, PPZ pretreatment significantly decreased ADR releasing index of
      SGC7901/ADR dose-dependently (P < 0.01). PPZ pretreatment also decreased cell
      viabilities of SGG7901 and SGC7901/ADR dose-dependently. After 24-h PPZ
      pretreatment, administration of chemotherapeutic agents demonstrated maximal
      cytotoxic effects on SGC7901 and SGC7901/ADR cells (P < 0.05). The resistance
      index in PPZ pretreatment group was significantly lower than that in non-PPZ
      pretreatment group (3.71 vs. 14.80). PPZ at concentration >10 ug/ml significantly
      decreased pHi in SGC7901 and SGC7901/ADR cells and diminished or reversed
      transmembrane pH gradient (P < 0.05). PPZ pretreatment also significantly
      inhibited protein expressions of V-ATPases, mTOR, HIF-1alpha, P-gp, and MRP1, and
      alter intracellular expressions in parent and ADR-resistant cells (P < 0.05). In
      vivo experiments further confirmed that PPZ pretreatment could enhance anti-tumor
      effects of ADR on xenografted tumor of nude mice and also improve the apoptotic
      index in xenografted tumor tissues. PPZ pretreatment enhances the cytotoxic
      effects of anti-tumor drugs on SGC7901 and reverse MDR of SGC7901/ADR by
      downregulating the V-ATPases/mTOR/HIF-1alpha/P-gp and MRP1 signaling pathway.

PMID- 22396187
TI  - [Interfere with contract physician's fee schedules? NO!].

PMID- 22396188
TI  - Novel generation of liquid crystalline photo-actuators based on stretched porous
      polyethylene films.
AB  - The preparation of photo-actuators based on stretched porous polyethylene and an
      azobenzene-containing liquid crystalline polymer network is reported for the
      first time. It is revealed that this kind of photo-actuator possesses the
      following advantages: the lack of a need for using aligning coatings and cells
      preparation, high deformation of the actuator and its complete reversibility,
      good mechanical properties, and relatively low cost of fabrication. In addition
      some kinetic and thermodynamic features of the bending and unbending processes
      have been studied.

PMID- 22396189
TI  - Factors associated with favorable response to hyperbaric oxygen therapy among
      patients presenting with iatrogenic cerebral arterial gas embolism.
AB  - BACKGROUND: Iatrogenic cerebral arterial gas embolism (CAGE) is an uncommon but
      potentially a fatal condition. Hyperbaric oxygen (HBO2) therapy is the only
      definitive treatment for patients with CAGE presenting with acute neurologic
      deficits. METHODS: We reviewed medical records and neuroimaging of consecutive
      CAGE patients treated with HBO2 at a state referral hyperbaric facility over a 22
      year period. We analyzed the effect of demographics, source of intra-arterial
      gas, signs and symptoms, results of imaging studies, time between event and HBO2
      treatment, and response to HBO2 treatment in 36 consecutive patients. Favorable
      outcome was defined by complete resolution or improvement of CAGE signs and
      symptoms at 24 h after HBO2 treatment. Unfavorable outcome was defined by
      unchanged or worsened neurologic signs and symptoms or in hospital death.
      RESULTS: A total of 26 (72%) of the 36 patients had favorable outcome. Patients
      with favorable outcome were younger compared to those with unfavorable outcome
      (mean age [years, SD] 44.7 +/- 17.8 vs. 58.1 +/- 24.1, p = 0.08). Cardiopulmonary
      symptoms were significantly more common in CAGE related to venous source of gas
      compared to arterial source (p = 0.024) but did not influence the rate of
      favorable outcomes. Adjusted multivariate analysis demonstrated that time from
      event to HBO2 <= 6 h (positively) and the presence of infarct/edema on head
      computerized tomography (CT)/magnetic resonance imaging (MRI) before HBO2
      (negatively) were independent predictors of favorable outcome at 24 h after HBO2
      treatment [odds ratio (OR) 9.08 confidence interval (CI) (1.13-72.69), p =
      0.0376, and (OR) 0.034 (CI) (0.002-0.58), p = 0.0200, respectively]. Two of the
      36 patients were treated with thrombolytics because of acute focal deficits and
      suspected ischemia-one with intravenous and the second with intra-arterial
      thrombolysis. The latter patient developed fatal intracerebral hemorrhage.
      CONCLUSIONS: A high proportion of CAGE patients treated with HBO2 had favorable
      outcomes. Time-to-HBO2 <= 6 h increased the odds of favorable outcome, whereas
      the presence of infarct/edema on CT/MRI scan before HBO2 reduced the odds of a
      favorable outcome. Timely diagnosis and differentiation from thrombo-embolic
      ischemic events appears to be an important determinant of successful HBO2
      treatment.

PMID- 22396190
TI  - Perioperative serum brain natriuretic peptide and cardiac troponin in elective
      intracranial surgery.
AB  - BACKGROUND: There are some intracranial insults which are associated with cardiac
      abnormalities. Studies of these abnormalities have never been carried out in
      elective intracranial neurosurgery for the removal of brain tumors. Our
      prospective study aims at quantifying serum cardiac troponin T (cTnT) and N
      terminal pro-brain natriuretic peptide (NT-proBNP) before and after elective
      intracranial neurosurgery for tumor resection in patients with no history of
      cardiac abnormality. METHODS: Pre- and postoperative serum cTnT and NT-proBNP
      were measured in 108 patients submitted to elective major intracranial surgery
      for the removal of neoplastic lesions. We tested potentially predictive models
      for these biomarker serum levels. RESULTS: cTnT was undetectable both before and
      after surgery. Median (IQR) basal NT-proBNP was 35 (18-69) pg/mL and 110 (51-191)
      pg/mL after surgery. In a multiple linear regression model, basal NT-proBNP was
      predicted by age, gender, BMI, and the presence of "mass effect" (midline shift
      or effaced perimesencephalic cisterns on preoperative CT scan) (whole model P <
      0.0001; R (2) = 0.3502; and Adjusted R (2) = 0.3247). Postoperative NT-proBNP
      increase was predicted by baseline NT-proBNP level (whole model P < 0.0001; R (2)
      = 0.5106; and Adjusted R (2) = 0.5052). CONCLUSION: An intracranial mass effect
      is associated with higher NT-proBNP serum levels in patients with a brain
      neoplasm. Following elective intracranial surgery for brain tumor resection NT
      proBNP values increase.

PMID- 22396191
TI  - Cerebral blood flow, brain tissue oxygen, and metabolic effects of decompressive
      craniectomy.
AB  - Decompressive craniectomy (DC) is used for patients with traumatic brain injury
      (TBI), malignant edema from middle cerebral artery infarction, aneurysmal
      subarachnoid hemorrhage, and non-traumatic intracerebral or cerebellar
      hemorrhage. The objective of the procedure is to relieve intractable intracranial
      hypertension and/or to prevent or reverse cerebral herniation. Decompressive
      craniectomy has been shown to decrease mortality in selected patients with large
      hemispheric infarction and to control intracranial pressure in addition to
      improving pressure-volume compensatory reserve after TBI. The clinical
      effectiveness of DC in patients with TBI is under evaluation in ongoing
      randomized clinical trials. There are several unresolved controversies regarding
      optimal candidate selection, timing, technique, and post-operative management and
      complications. The nature and temporal progression of alterations in cerebral
      blood flow, brain tissue oxygen, and microdialysis markers have only recently
      been researched. Elucidating the pathophysiology of pressure-flow and cerebral
      hemodynamic consequences of DC could assist in optimizing clinical decision
      making and further defining the role of decompressive craniectomy.

PMID- 22396193
TI  - Functionalized synthetic biodegradable polymer scaffolds for tissue engineering.
AB  - Scaffolds (artificial ECMs) play a pivotal role in the process of regenerating
      tissues in 3D. Biodegradable synthetic polymers are the most widely used
      scaffolding materials. However, synthetic polymers usually lack the biological
      cues found in the natural extracellular matrix. Significant efforts have been
      made to synthesize biodegradable polymers with functional groups that are used to
      couple bioactive agents. Presenting bioactive agents on scaffolding surfaces is
      the most efficient way to elicit desired cell/material interactions. This paper
      reviews recent advancements in the development of functionalized biodegradable
      polymer scaffolds for tissue engineering, emphasizing the syntheses of functional
      biodegradable polymers, and surface modification of polymeric scaffolds.

PMID- 22396192
TI  - The oxygen reactivity index and its relation to sensor technology in patients
      with severe brain lesions.
AB  - BACKGROUND: The oxygen reactivity index (ORx) has been introduced to assess the
      status of cerebral autoregulation after traumatic brain injury (TBI) or
      subarachnoid hemorrhage (SAH). Currently, there is some controversy about whether
      the ORx depends on the type of PbrO2-sensor technology used for its calculation.
      To examine if the probe technology does matter, we compared the ORx and the
      resulting optimal cerebral perfusion pressures (CPPopt) of simultaneously
      implanted Licox (CC1.SB, Integra Neuroscience, France) and Neurovent-PTO
      (Raumedic, Germany) probes in patients after aneurysmal SAH or severe TBI.
      METHODS: Licox and Raumedic probes were implanted side by side in 11 patients
      after TBI or SAH. ORx and CPPopt were recorded continuously. The equivalence of
      both probes was examined using Bland-Altman analyses. RESULTS: The mean
      difference in ORx was 0.1, with Licox producing higher values. The limits of
      agreement regarding ORx ranged from -0.6 to +0.7. When both probes' ORx values
      were compared in each patient, no specific pattern in their relationship was
      seen. The mean difference in CPPopt was 0 mmHg with limits of agreement between 
      16.5 and +16.4 mmHg. CONCLUSIONS: Owing to the rather limited number of patients,
      we view the results of this study as preliminary. The main result is that Licox
      and Raumedic showed consistent differences in ORx and CPPopt. Therefore, ORx
      values of both probes cannot be interchanged and should not be viewed as
      equivalent. This should be taken into consideration when discussing ORx data
      generated by different PbrO2 probe types.

PMID- 22396194
TI  - Beta-decomposition for the volume and area of the union of three-dimensional
      balls and their offsets.
AB  - Given a set of spherical balls, called atoms, in three-dimensional space, its
      mass properties such as the volume and the boundary area of the union of the
      atoms are important for many disciplines, particularly for computational
      chemistry/biology and structural molecular biology. Despite many previous
      studies, this seemingly easy problem of computing mass properties has not been
      well-solved. If the mass properties of the union of the offset of the atoms are
      to be computed as well, the problem gets even harder. In this article, we propose
      algorithms that compute the mass properties of both the union of atoms and their
      offsets both correctly and efficiently. The proposed algorithms employ an
      approach, called the Beta-decomposition, based on the recent theory of the beta
      complex. Given the beta-complex of an atom set, these algorithms decompose the
      target mass property into a set of primitives using the simplexes of the beta
      complex. Then, the molecular mass property is computed by appropriately summing
      up the mass property corresponding to each simplex. The time complexity of the
      proposed algorithm is O(m) in the worst case where m is the number of simplexes
      in the beta-complex that can be efficiently computed from the Voronoi diagram of
      the atoms. It is known in R(3) that m = O(n) on average for biomolecules and m =
      O(n(2)) in the worst case for general spheres where n is the number of atoms. The
      theory is first introduced in R(2) and extended to R(3). The proposed algorithms
      were implemented into the software BetaMass and thoroughly tested using molecular
      structures available in the Protein Data Bank. BetaMass is freely available at
      the Voronoi Diagram Research Center web site.

PMID- 22396195
TI  - Serum long chain n-3 fatty acids (EPA and DHA) in the pregnant mother are
      independent of risk of type 1 diabetes in the offspring.
AB  - BACKGROUND: This article aims to study whether higher proportions of the long
      chain n-3 fatty acids eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA)
      in the phospholipid fraction of serum samples in pregnancy were associated with a
      lower risk of childhood onset type 1 diabetes in the offspring. METHODS: In a
      prospective cohort of nearly 30 000 pregnant women who gave birth in Norway
      during 1992-1994, we analysed serum samples from 89 women whose child developed
      type 1 diabetes and was included in the nationwide Norwegian Childhood Diabetes
      Registry and 125 randomly selected women whose child did not develop type 1
      diabetes before 15 years of age. Specific fatty acids were expressed as the
      proportion of total fatty acids (g/100 g) in the phospholipid fraction in serum
      analysed using solid phase extraction and gas chromatography with flame
      ionization detection. RESULTS: There was no significant association between EPA
      or DHA in maternal serum and risk of type 1 diabetes in the offspring. Odds ratio
      (OR) for upper versus lower quartile of EPA was 0.75 [95% confidence interval
      (CI) 0.34-1.65], test for trend p = 0.4, and for DHA OR = 0.71 (95% CI 0.33
      1.53), test for trend p = 0.6. No significant association was found for the sum
      of n-3 fatty acids, or for n-6/n-3 ratio in the mother with risk of type 1
      diabetes in the offspring. CONCLUSIONS: Our data did not support the hypothesis
      that higher proportions of maternal EPA or DHA during pregnancy are associated
      with a lower risk of type 1 diabetes in the offspring.

PMID- 22396197
TI  - Clinical trials of HDL cholesterol-raising therapy: what have we learned about
      the HDL hypothesis from AIM-HIGH?

PMID- 22396196
TI  - The j-point phenomenon in aggressive therapy of hypertension: new insights.
AB  - In the era of aggressive control of cardiovascular risk factors such as
      hypertension, the mantra of "lower is better" has taken a strong foothold.
      Although there is clear epidemiologic evidence that lower blood pressure improves
      specific organ-related outcomes, this rule does not apply to all patients and
      definitely not all target organs. The concept of J-curve or adverse outcomes at
      lower blood pressure has been proposed for more than three decades but has
      recently come under increasing scrutiny. Specifically, a relationship between
      adverse cardiovascular outcomes and low diastolic blood pressure has been
      observed in multiple clinical trials. In this article we review the advances in
      understanding of the J-curve phenomenon and include a discussion on specific
      populations that might be at higher risk due to the J-curve relationship.

PMID- 22396198
TI  - Runt-related transcription factor 2 in human colon carcinoma: a potent prognostic
      factor associated with estrogen receptor.
AB  - Runt-related transcription factor 2 (RUNX2) belongs to the RUNX family of
      heterodimeric transcription factors, and is mainly associated with osteogenesis.
      Previous in vitro studies demonstrated that RUNX2 increased the cell
      proliferation of mouse and rat colon carcinoma cells but the status of RUNX2 has
      remained unknown in human colon carcinoma. Therefore, we examined clinical
      significance and biological functions of RUNX2 in colon carcinoma. RUNX2
      immunoreactivity was examined in 157 colon carcinoma tissues using
      immunohistochemistry. RUNX2 immunoreactivity was evaluated as percentage of
      positive carcinoma cells [i.e., labeling index (LI)]. We used SW480 and DLD-1
      human colon carcinoma cells, expressing estrogen receptor-beta (ER) in subsequent
      in vitro studies. RUNX2 immunoreactivity was detected in colon carcinoma cells,
      and the median value of RUNX2 LI was 67%. RUNX2 LI was significantly associated
      with Dukes' stage, liver metastasis and ERbeta status. In addition, RUNX2 LI was
      significantly associated with adverse clinical outcome of the colon carcinoma
      patients, and turned out an independent prognostic factor following multivariate
      analysis. Results of in vitro studies demonstrated that both SW480 and DLD-1
      cells transfected with small interfering RNA against RUNX2 significantly
      decreased their cell proliferation, migration and invasive properties. In
      addition, RUNX2 mRNA level was significantly decreased by ER antagonist in these
      two cells. These findings all suggest that RUNX2 is a potent prognostic factor in
      human colon carcinoma patients through the promotion of cell proliferation and
      invasion properties, and is at least partly upregulated by estrogen signals
      through ERbeta of carcinoma cells.

PMID- 22396199
TI  - Sustained antidiabetic effects of a berberine-containing Chinese herbal medicine
      through regulation of hepatic gene expression.
AB  - Diabetes and obesity are complex diseases associated with insulin resistance and
      fatty liver. The latter is characterized by dysregulation of the Akt, AMP
      activated protein kinase (AMPK), and IGF-I pathways and expression of microRNAs
      (miRNAs). In China, multicomponent traditional Chinese medicine (TCM) has been
      used to treat diabetes for centuries. In this study, we used a three-herb,
      berberine-containing TCM to treat male Zucker diabetic fatty rats. TCM showed
      sustained glucose-lowering effects for 1 week after a single-dose treatment. Two
      week treatment attenuated insulin resistance and fatty degeneration, with
      hepatocyte regeneration lasting for 1 month posttreatment. These beneficial
      effects persisted for 1 year after 1-month treatment. Two-week treatment with TCM
      was associated with activation of AMPK, Akt, and insulin-like growth factor
      binding protein (IGFBP)1 pathways, with downregulation of miR29-b and expression
      of a gene network implicated in cell cycle, intermediary, and NADPH metabolism
      with normalization of CYP7a1 and IGFBP1 expression. These concerted changes in
      mRNA, miRNA, and proteins may explain the sustained effects of TCM in favor of
      cell survival, increased glucose uptake, and lipid oxidation/catabolism with
      improved insulin sensitivity and liver regeneration. These novel findings suggest
      that multicomponent TCM may be a useful tool to unravel genome regulation and
      expression in complex diseases.

PMID- 22396200
TI  - Placental adiponectin gene DNA methylation levels are associated with mothers'
      blood glucose concentration.
AB  - Growing evidence suggests that epigenetic profile changes occurring during fetal
      development in response to in utero environment variations could be one of the
      mechanisms involved in the early determinants of adult chronic diseases. In this
      study, we tested whether maternal glycemic status is associated with the
      adiponectin gene (ADIPOQ) DNA methylation profile in placenta tissue, in maternal
      circulating blood cells, and in cord blood cells. We found that lower DNA
      methylation levels in the promoter of ADIPOQ on the fetal side of the placenta
      were correlated with higher maternal glucose levels during the second trimester
      of pregnancy (2-h glucose after the oral glucose tolerance test; r(s) <= -0.21, P
      < 0.05). Lower DNA methylation levels on the maternal side of the placenta were
      associated with higher insulin resistance index (homeostasis model assessment of
      insulin resistance) during the second and third trimesters of pregnancy (r(s) <= 
      0.27, P < 0.05). Finally, lower DNA methylation levels were associated with
      higher maternal circulating adiponectin levels throughout pregnancy (r(s) <= 
      0.26, P < 0.05). In conclusion, the ADIPOQ DNA methylation profile was associated
      with maternal glucose status and with maternal circulating adiponectin
      concentration. Because adiponectin is suspected to have insulin-sensitizing
      proprieties, these epigenetic adaptations have the potential to induce sustained
      glucose metabolism changes in the mother and offspring later in life.

PMID- 22396201
TI  - A novel method to measure glucose uptake and myosin heavy chain isoform
      expression of single fibers from rat skeletal muscle.
AB  - Skeletal muscle includes many individual fibers with diverse phenotypes. A
      barrier to understanding muscle glucose uptake at the cellular level has been the
      absence of a method to measure glucose uptake by single fibers from mammalian
      skeletal muscle. This study's primary objective was to develop a procedure to
      measure glucose uptake by single fibers from rat skeletal muscle. Rat
      epitrochlearis muscles were incubated ex vivo with [(3)H]-2-deoxy-d-glucose, with
      or without insulin or AICAR, before isolation of ~10-30 single fibers from each
      muscle. Fiber type (myosin heavy chain [MHC] isoform) and glucose uptake were
      determined for each single fiber. Insulin-stimulated glucose uptake (which was
      cytochalasin B inhibitable) varied according to MHC isoform expression, with ~2
      fold greater values for IIA versus IIB or IIX fibers and ~1.3-fold greater for
      hybrid (IIB/X) versus IIB fibers. In contrast, AICAR-stimulated glucose uptake
      was ~1.5-fold greater for IIB versus IIA fibers. A secondary objective was to
      assess insulin resistance of single fibers from obese versus lean Zucker rats.
      Genotype differences were observed for insulin-stimulated glucose uptake and
      inhibitor kappaB (IkappaB)-beta abundance in single fibers (obese less than
      lean), with decrements for glucose uptake (44-58%) and IkappaB-beta (25-32%) in
      each fiber type. This novel method creates a unique opportunity for future
      research focused on understanding muscle glucose uptake at the cellular level.

PMID- 22396202
TI  - Retinoic acid upregulates preadipocyte genes to block adipogenesis and suppress
      diet-induced obesity.
AB  - Retinoic acid (RA) protects mice from diet-induced obesity. The activity is
      mediated in part through activation of the nuclear receptors RA receptors (RARs)
      and peroxisome proliferator-activated receptor beta/delta and their associated
      binding proteins cellular RA binding protein type II (CRABP-II) and fatty acid
      binding protein type 5 in adipocytes and skeletal muscle, leading to enhanced
      lipid oxidation and energy dissipation. It was also reported that RA inhibits
      differentiation of cultured preadipocytes. However, whether the hormone
      suppresses adipogenesis in vivo and how the activity is propagated remained
      unknown. In this study, we show that RA inhibits adipocyte differentiation by
      activating the CRABP-II/RARgamma path in preadipose cells, thereby upregulating
      the expression of the adipogenesis inhibitors Pref-1, Sox9, and Kruppel-like
      factor 2 (KLF2). In turn, KLF2 induces the expression of CRABP-II and RARgamma,
      further potentiating inhibition of adipocyte differentiation by RA. The data also
      indicate that RA suppresses adipogenesis in vivo and that the activity
      significantly contributes to the ability of the hormone to counteract diet
      induced obesity.

PMID- 22396203
TI  - Short-term hyperinsulinemia and hyperglycemia increase myocardial lipid content
      in normal subjects.
AB  - Increased myocardial lipid content (MYCL) recently has been linked to the
      development of cardiomyopathy in diabetes. In contrast to steatosis in skeletal
      muscle and liver, previous investigations could not confirm a link between MYCL
      and insulin resistance. Thus, we hypothesized that cardiac steatosis might
      develop against the background of the metabolic environment typical for
      prediabetes and early type 2 diabetes: combined hyperglycemia and
      hyperinsulinemia. Therefore, we aimed to prove the principle that acute
      hyperglycemia (during a 6-h clamp) affects MYCL and function (assessed by (1)H
      magnetic resonance spectroscopy and imaging) in healthy subjects (female
      subjects: n = 8, male subjects: n = 10; aged 28 +/- 5 years; BMI 22.4 +/- 2.6
      kg/m(2)). Combined hyperglycemia (202.0 +/- 10.6 mg/dL) and hyperinsulinemia
      (110.6 +/- 59.0 MUU/mL) were, despite insulin-mediated suppression of free fatty
      acids, associated with a 34.4% increase in MYCL (baseline: 0.20 +/- 0.17%, clamp:
      0.26 +/- 0.22% of water signal; P = 0.0009), which was positively correlated with
      the area under the curve of insulin (R = 0.59, P = 0.009) and C-peptide (R =
      0.81, P < 0.0001) during the clamp. Furthermore, an increase in ejection fraction
      (P < 0.0001) and a decrease in end-systolic volume (P = 0.0002) were observed,
      which also were correlated with hyperinsulinemia. Based on our findings, we
      conclude that combined hyperglycemia and hyperinsulinemia induce short-term
      myocardial lipid accumulation and alterations in myocardial function in normal
      subjects, indicating that these alterations might be directly responsible for
      cardiac steatosis in metabolic diseases.

PMID- 22396204
TI  - Glycotoxin and autoantibodies are additive environmentally determined predictors
      of type 1 diabetes: a twin and population study.
AB  - In type 1 diabetes, diabetes-associated autoantibodies, including islet cell
      antibodies (ICAs), reflect adaptive immunity, while increased serum N(epsilon)
      carboxymethyl-lysine (CML), an advanced glycation end product, is associated with
      proinflammation. We assessed whether serum CML and autoantibodies predicted type
      1 diabetes and to what extent they were determined by genetic or environmental
      factors. Of 7,287 unselected schoolchildren screened, 115 were ICA(+) and were
      tested for baseline CML and diabetes autoantibodies and followed (for median 7
      years), whereas a random selection (n = 2,102) had CML tested. CML and diabetes
      autoantibodies were determined in a classic twin study of twin pairs discordant
      for type 1 diabetes (32 monozygotic, 32 dizygotic pairs). CML was determined by
      enzyme-linked immunosorbent assay, autoantibodies were determined by
      radioimmunoprecipitation, ICA was determined by indirect immunofluorescence, and
      HLA class II genotyping was determined by sequence-specific oligonucleotides. CML
      was increased in ICA(+) and prediabetic schoolchildren and in diabetic and
      nondiabetic twins (all P < 0.001). Elevated levels of CML in ICA(+) children were
      a persistent, independent predictor of diabetes progression, in addition to
      autoantibodies and HLA risk. In twins model fitting, familial environment
      explained 75% of CML variance, and nonshared environment explained all
      autoantibody variance. Serum CML, a glycotoxin, emerged as an environmentally
      determined diabetes risk factor, in addition to autoimmunity and HLA genetic
      risk, and a potential therapeutic target.

PMID- 22396205
TI  - Stress augments insulin resistance and prothrombotic state: role of visceral
      adipose-derived monocyte chemoattractant protein-1.
AB  - Stressors contribute to thrombosis and insulin resistance. Since obesity-related
      adipose inflammation is also involved in these pathological states, we assumed
      that stress correlates with adipose inflammation. Male mice were subjected to 2
      week intermittent restraint stress. Expression of plasma lipids,
      monocyte/macrophage markers (CD11b, CD68, and F4/80), proinflammatory cytokines
      (monocyte chemoattractant protein-1 [MCP-1], tumor necrosis factor-alpha, and
      interleukin-6), adiponectin, heat shock protein 70.1 (HSP70.1), and coagulation
      factors (plasminogen activation inhibitor-1 [PAI-1] and tissue factor [TF]) in
      blood and inguinal white adipose tissue (WAT) was determined using
      immunohistochemistry, enzyme-linked immunosorbent assay, and RT-PCR,
      respectively. Glucose metabolism was assessed by glucose tolerance tests (GTTs)
      and insulin tolerance tests, and expression of insulin receptor substrate-1 (IRS
      1) and glucose transporter 4 (GLUT4) in WAT. To examine effects of MCP-1
      blockade, animals were treated with control or neutralizing antibody, or
      transplanted with control or 7ND (dominant-negative form of MCP-1)-overexpressing
      adipose-derived stromal cells (ADSCs). Stress increased monocyte accumulation,
      free fatty acids, proinflammatory cytokine, and HSP70.1 and reduced adiponectin.
      Adipose stromal cells highly expressed MCP-1. The stress-induced adipose
      inflammation increased PAI-1 and TF but did not give rise to thrombus formation.
      Without any changes in GTT, stress worsened insulin sensitivity and decreased IRS
      1 and GLUT4 in WAT. Neutralizing antibody and 7ND-ADSCs reversed stress-induced
      adipose inflammation, procoagulant state, and insulin resistance. Stress evoked
      adipose inflammation to increase coagulation factors and impair insulin
      sensitivity through adipose-derived MCP-1.

PMID- 22396206
TI  - The radioprotective 105/MD-1 complex contributes to diet-induced obesity and
      adipose tissue inflammation.
AB  - Recent accumulating evidence suggests that innate immunity is associated with
      obesity-induced chronic inflammation and metabolic disorders. Here, we show that
      a Toll-like receptor (TLR) protein, radioprotective 105 (RP105)/myeloid
      differentiation protein (MD)-1 complex, contributes to high-fat diet (HFD)
      induced obesity, adipose tissue inflammation, and insulin resistance. An HFD
      dramatically increased RP105 mRNA and protein expression in stromal vascular
      fraction of epididymal white adipose tissue (eWAT) in wild-type (WT) mice. RP105
      mRNA expression also was significantly increased in the visceral adipose tissue
      of obese human subjects relative to nonobese subjects. The RP105/MD-1 complex was
      expressed by most adipose tissue macrophages (ATMs). An HFD increased RP105/MD-1
      expression on the M1 subset of ATMs that accumulate in eWAT. Macrophages also
      acquired this characteristic in coculture with 3T3-L1 adipocytes. RP105 knockout
      (KO) and MD-1 KO mice had less HFD-induced adipose tissue inflammation, hepatic
      steatosis, and insulin resistance compared with wild-type (WT) and TLR4 KO mice.
      Finally, the saturated fatty acids, palmitic and stearic acids, are endogenous
      ligands for TLR4, but they did not activate RP105/MD-1. Thus, the RP105/MD-1
      complex is a major mediator of adipose tissue inflammation independent of TLR4
      signaling and may represent a novel therapeutic target for obesity-associated
      metabolic disorders.

PMID- 22396207
TI  - Loss of AMP-activated protein kinase-alpha2 impairs the insulin-sensitizing
      effect of calorie restriction in skeletal muscle.
AB  - Whether the well-known metabolic switch AMP-activated protein kinase (AMPK) is
      involved in the insulin-sensitizing effect of calorie restriction (CR) is
      unclear. In this study, we investigated the role of AMPK in the insulin
      sensitizing effect of CR in skeletal muscle. Wild-type (WT) and AMPK-alpha2(-/-)
      mice received ad libitum (AL) or CR (8 weeks at 60% of AL) feeding. CR increased
      the protein level of AMPK-alpha2 and phosphorylation of AMPK-alpha2. In WT and
      AMPK-alpha2(-/-) mice, CR induced comparable changes of body weight, fat pad
      weight, serum triglycerides, serum nonesterified fatty acids, and serum leptin
      levels. However, decreasing levels of fasting/fed insulin and fed glucose were
      observed in WT mice but not in AMPK-alpha2(-/-) mice. Moreover, CR-induced
      improvements of whole-body insulin sensitivity (evidenced by glucose tolerance
      test/insulin tolerance test assays) and glucose uptake in skeletal muscle tissues
      were abolished in AMPK-alpha2(-/-) mice. Furthermore, CR-induced activation of
      Akt-TBC1D1/TBC1D4 signaling, inhibition of mammalian target of rapamycin-S6K1
      insulin receptor substrate-1 pathway, and induction of nicotinamide
      phosphoribosyltransferase-NAD(+)-sirtuin-1 cascade were remarkably impaired in
      AMPK-alpha2(-/-) mice. CR serum increased stability of AMPK-alpha2 protein via
      inhibiting the X chromosome-linked ubiquitin-specific protease 9-mediated
      ubiquitylation of AMPK-alpha2. Our results suggest that AMPK may be modulated by
      CR in a ubiquitylation-dependent manner and acts as a chief dictator for the
      insulin-sensitizing effects of CR in skeletal muscle.

PMID- 22396208
TI  - Cofilin is required for organization of sarcomeric actin filaments in chicken
      skeletal muscle cells.
AB  - Cofilin is an actin regulatory protein that plays a critical role in actin
      filament dynamics in a variety of cells. We have previously demonstrated that
      excess cofilin in skeletal muscle cells leads to disruption of actin filaments,
      followed by actin-cofilin rod formation in the cytoplasm. In this study, to
      further clarify the role of cofilin in actin assembly during myofibrillogenesis,
      cofilin expression was suppressed in cultured chicken skeletal muscle cells.
      First, we confirmed that turnover of cofilin in myotubes was much higher than
      that of actin, and that the cofilin level could be decreased drastically within 2
      days when cofilin de novo synthesis was suppressed. Next, cofilin expression in
      individual myotubes was suppressed by introducing antisense morpholino
      oligonucleotides into the cells by microinjection. Cofilin depletion at the early
      phase of myofibrillogenesis caused abnormal actin aggregates in myotubes and
      impaired actin organization into cross-striated myofibril structures. However,
      when cofilin expression was suppressed in developed myotubes, actin localization
      in striated myofibrils was scarcely affected. These results indicate that cofilin
      plays a critical role in the regulation of actin assembly at the early process of
      myofibrillogenesis.

PMID- 22396209
TI  - Effects of stick design features on perceptions of characteristics of cigarettes.
AB  - OBJECTIVE: To examine the extent (if any) that cigarette stick dimension, tipping
      paper design and other decorative design/branding have on Australian smokers'
      perceptions of those cigarettes. METHODS: An internet survey of 160 young
      Australian adult ever-smokers who were shown computer images of three sets of
      cigarette sticks--five sticks of different lengths and diameters (set A), five
      sticks with different tipping paper design (set B) and four sticks of different
      decorative design (set C). Branding was a between-subjects randomised condition
      for set C. For each set, respondents ranked sticks on most and least attractive,
      highest and lowest quality and strongest and weakest taste. RESULTS: Cigarette
      sticks were perceived as different on attractiveness, quality and strength of
      taste. Standard stick length/diameter was perceived as the most attractive and
      highest quality stick, with men more inclined to rate a slim stick as less
      attractive. A stick with a cork-patterned tipping paper and a gold band was seen
      as most attractive, of highest quality and strongest in taste compared to other
      tipping designs. Branded sticks were seen as more attractive, higher in quality
      and stronger tasting than non-branded designs, regardless of brand, although the
      effects were stronger for a prestige compared with a budget brand. CONCLUSIONS:
      Characteristics of the cigarette stick affect smokers' perceptions of the
      attributes of those cigarettes and thus are a potential means by which product
      differentiation can occur. A comprehensive policy to eliminate promotional
      aspects of cigarette design and packaging needs to include rules about stick
      design.

PMID- 22396210
TI  - Reorganization of the DNA-nuclear matrix interactions in a 210 kb genomic region
      centered on c-myc after DNA replication in vivo.
AB  - In the interphase nucleus of metazoan cells DNA is organized in supercoiled loops
      anchored to a nuclear matrix (NM). DNA loops are operationally classified in
      structural and facultative. Varied evidence indicates that DNA replication occurs
      in replication foci organized upon the NM and that structural DNA loops may
      correspond to the replicons in vivo. In normal rat liver the hepatocytes are
      arrested in G0 but synchronously re-enter the cell cycle after partial
      hepatectomy leading to liver regeneration. Using this model we have previously
      determined that the DNA loops corresponding to a gene-rich genomic region move in
      a sequential fashion towards the NM during replication and then return to their
      original configuration in newly quiescent cells, once liver regeneration has been
      achieved. In the present work we determined the organization into structural DNA
      loops of a gene-poor region centered on c-myc and tracked-down its movement at
      the peak of S phase and after the return to cellular quiescence during and after
      liver regeneration. The results confirmed that looped DNA moves towards the NM
      during replication but in this case the configuration of the gene-poor region
      into DNA loops becomes reorganized and after replication only the loop containing
      c-myc resembles the original in the control G0 hepatocytes. Our results suggest
      that the local chromatin configuration around potentially active genes
      constraints the formation of specific structural DNA loops after DNA replication,
      while in non-coding regions the structural DNA loops are only loosely determined
      after DNA replication by structural constraints that modulate the DNA-NM
      interactions.

PMID- 22396211
TI  - [Will cardiac CT replace coronary catheterization?].

PMID- 22396212
TI  - Prenylation of Rho G-proteins: a novel mechanism regulating gene expression and
      protein stability in human trabecular meshwork cells.
AB  - Endogenous prenylation with sesquiterpene or diterpene isoprenoids facilitates
      membrane localization and functional activation of small monomeric GTP-binding
      proteins. A direct effect of isoprenoids on regulation of gene expression and
      protein stability has also been proposed. In this study, we determined the role
      of sesquiterpene or diterpene isoprenoids on the regulation of Rho G-protein
      expression, activation, and stability in human trabecular meshwork (TM) cells. In
      both primary and transformed human TM cells, limiting endogenous isoprenoid
      synthesis with lovastatin, a potent HMG-CoA reductase inhibitor, elicited marked
      increases in RhoA and RhoB mRNA and protein content. The effect of lovastatin was
      dose-dependent with newly synthesized inactive protein accumulating in the
      cytosol. Supplementation with geranylgeranyl pyrophosphate (GGPP) prevented,
      while inhibition of geranylgeranyl transferase-I mimicked, the effects of
      lovastatin on RhoA and RhoB protein content. Similarly, lovastatin-dependent
      increases in RhoA and RhoB mRNA expression were mimicked by geranylgeranyl
      transferase-I inhibition. Interestingly, GGPP supplementation selectively
      promoted the degradation of newly synthesized Rho proteins which was mediated, in
      part, through the 20S proteasome. Functionally, GGPP supplementation prevented
      lovastatin-dependent decreases in actin stress fiber organization while
      selectively facilitating the subcellular redistribution of accumulated Rho
      proteins from the cytosol to the membrane and increasing RhoA activation. Post
      translational prenylation with geranylgeranyl diterpenes selectively facilitates
      the expression, membrane translocation, functional activation, and turnover of
      newly synthesized Rho proteins. Geranylgeranyl prenylation represents a novel
      mechanism by which active Rho proteins are targeted to the 20S proteasome for
      degradation in human TM cells.

PMID- 22396214
TI  - Impact of the closure of a large urban medical center: a quantitative assessment
      (part II).
AB  - This community health needs assessment-the second part of a mixed-methods project
      sought to quantitatively determine the impact of the closure of St. Vincent's
      Medical Center, a large not-for-profit hospital in NYC on individuals who used
      its services. Findings from a community survey disseminated to the broader
      community affected by the closure of this hospital are described. The questions
      covered topics including demographics, health status, experiences accessing
      health care pre- and post-hospital closure, access to medical records,
      prescriptions, etc. The majority of respondents are from the community
      immediately surrounding the hospital. Almost 50% report having a physical or
      mental health condition requiring regular care; roughly 64% had a doctor
      affiliated with St. Vincent's and 68% currently see the same doctor as before the
      hospital closed. With regard to service utilization, 74% reported having sought
      services at St. Vincent's in the past 5 years. Of these, the emergency department
      was the most commonly used service (75%), followed by specialty tests (32%),
      inpatient care (30%), and outpatient services (22%). The majority of ratings of
      services at St. Vincent's were "excellent" or "very good." Conversely, 65% of
      former St. Vincent's users reported more difficulty obtaining health care post
      closure. Of the 11% who have tried to access their medical records, 30% have not
      been able to obtain their records and 42% report their attempt as being "somewhat
      difficult" or "very difficult." Over 50% report spending more time traveling or
      traveling further to get to their healthcare provider; and over one third report
      waiting longer to get an appointment, or to be seen when at an appointment.
      Bivariate analyses revealed that certain subgroups of respondents had
      significantly worse negative experiences associated with the closure of the
      hospital. Specifically, individuals with a health condition were more likely to
      have visited an ER since St. Vincent's closed, and now travel further and spend
      more time traveling to their health care provider, compared to those without a
      physical and/or mental health condition. Similarly, a greater proportion of
      respondents who had a doctor affiliated with St. Vincent's reported greater
      challenges accessing care since the closing, compared to those who did not have a
      doctor affiliated with St. Vincent's (e.g., waiting longer to get an
      appointment). Finally, the same health care challenges were being experienced by
      those who are not seeing the same doctor as prior to the closing.

PMID- 22396215
TI  - The ongoing pursuit of a prophylactic HSV vaccine.
AB  - HSV is among the most common human pathogens in the world. It is known to cause
      painful, persistent skin lesions, while also being the most common cause of fatal
      non-epidemic encephalitis as well as the leading cause of corneal blindness. The
      development of prophylactic vaccines could substantially reduce global health
      problems associated with HSV. So far, HSV vaccine strategies have shown
      noticeable efficacy in early development during preclinical phases but remained
      unsuccessful or unproven in human trials. New understanding of how the immune
      system mounts a defence against HSV offers practical strategies for vaccine
      development. A number of promising vaccine candidates are currently awaiting
      clinical development or already undergoing clinical testing. Therefore, this is a
      suitable time to assess the progress of HSV vaccine development and consider
      existing challenges and future improvements needed to achieve an effective
      prophylactic HSV vaccine.

PMID- 22396213
TI  - Multiple roles for frequenin/NCS-1 in synaptic function and development.
AB  - The calcium-binding protein frequenin (Frq), discovered in the fruit fly
      Drosophila, and its mammalian homologue neuronal calcium sensor 1 (NCS-1) have
      been reported to affect several aspects of synaptic transmission, including basal
      levels of neurotransmission and short- and long-term synaptic plasticities.
      However, discrepant reports leave doubts about the functional roles of these
      conserved proteins. In this review, we attempt to resolve some of these seemingly
      contradictory reports. We discuss how stimulation protocols, sources of calcium
      (voltage-gated channels versus internal stores), and expression patterns
      (presynaptic versus postsynaptic) of Frq may result in the activation of various
      protein targets, leading to different synaptic effects. In addition, the
      potential interactions of Frq's C-terminal and N-terminal domains with other
      proteins are discussed. Frq also has a role in regulating neurite outgrowth,
      axonal regeneration, and synaptic development. We examine whether the effects of
      Frq on neurotransmitter release and neurite outgrowth are distinct or
      interrelated through homeostatic mechanisms. Learning and memory are affected by
      manipulations of Frq probably through changes in synaptic transmission and
      neurite outgrowth, raising the possibility that Frq may be implicated in human
      pathological conditions, including schizophrenia, bipolar disorder, and X-linked
      mental retardation.

PMID- 22396216
TI  - Temperature dependence of vibrational modes of CH3?C?C(ads) and I(ads) coadsorbed
      on Ag(111): ab initio molecular dynamics approach.
AB  - Ab initio molecular dynamics simulations accompanied by a Fourier transform of
      the dipole moment (aligned perpendicular to the surface) autocorrelation function
      are implemented to investigate the temperature-dependent infrared (IR) active
      vibrational modes of CH3?C(beta)?C(alpha)(ads) and I(ads) when coadsorbed on an
      Ag(111) surface at 200 and 400 K, respectively. The analytic scheme of the
      Fourier transform of a structural coordinate autocorrelation function is used to
      identify two distinguishable IR active peaks of C(beta)?C(alpha) stretching,
      which are characterized by two types of dynamic motion of adsorbed
      CH3?C(beta)?C(alpha)(ads) at 200 K, namely, the motion of the tilted
      ?C?C(beta)?C(alpha)? axis and the motion of the stand-up ?C?C(beta)?C(alpha)?
      axis. These two recognisable IR active peaks of C(beta)?C(alpha) stretching are
      gradually merged into one peak as a result of the dominant motion of the stand-up
      ?C?C(beta)?C(alpha)? axis as the temperature increases from 200 to 400 K. The
      calculated intensities of the IR active peaks of the asymmetrical deformation
      mode of CH3 and the asymmetrical stretching mode of CH3, with their dynamic
      dipole moments nearly perpendicular to the ?C?C(beta)?C(alpha)? axis, become
      relatively weak; however, the symmetrical deformation mode of CH3 and the
      symmetrical stretching mode of CH3, with their dynamic dipole moments randomly
      directed away from the ?C?C(beta)?C(alpha)? axis, will not have direct
      correspondence between the intensities of their IR active peaks and the angle
      between the Ag(111) surface and the ?C?C(beta)?C(alpha)? axis as the temperature
      increases from 200 to 400 K. Finally, the increased flipping from the motion of
      the tilted ?C?C(beta)?C(alpha)? axis to the motion of the stand-up
      ?C?C(beta)?C(alpha)? axis followed by its diffusion, resulting from the
      increasing temperature from 200 to 400 K or even higher, seems to be the initial
      event that initiates the alkyne self-coupling reaction that leads to the final
      production of H3C?C?C?C?C?CH3.

PMID- 22396218
TI  - Using storage organelles for the accumulation and encapsulation of recombinant
      proteins.
AB  - Plants have been used to produce many diverse and valuable recombinant proteins,
      including subunit vaccines, antibodies and antibody fragments, hormones, blood
      products, cytokines, and enzymes. Different plant species and platforms have been
      explored as production hosts, each with unique properties in terms of the gene
      transfer method, production time, environmental containment, scalability,
      downstream processing strategy, protein folding and accumulation, and overall
      costs. Seed-based systems have many advantages because they exploit the natural
      storage properties of seeds, which facilitate batch processing and distribution.
      Seeds possess specialized storage organelles that may be used to accumulate
      recombinant proteins, offering stability both in planta and after harvest in the
      final preparation/formulation. The post-harvest stabilizing effect of seeds
      allows recombinant subunit vaccines and antibodies to be delivered via the
      mucosal route because they are better able to withstand this harsh
      microenvironment when protected by the plant matrix. Native storage organelles
      such as starch granules and protein bodies offer this protective effect, but
      protein storage organelles can also be induced ectopically in vegetative tissues.
      In this paper, we discuss the technical capabilities of storage organelle-based
      expression platforms and their potential applications.

PMID- 22396219
TI  - Is choice of care compatible with integrated health care? An exploratory study in
      Sweden.
AB  - Competitive and integrative policy actions are simultaneously being promoted in
      Swedish primary care; citizens' choice of care is launched while primary care is
      expected to integrate its activities with other providers for the creation of
      'local health care'. Competition tends, however, to fragment the provision of
      services. The aim of this study is, accordingly, to explore whether or not these
      policies are compatible in practice. For this purpose, strategically designed
      group interviews were conducted with citizens. When citizens make active choices,
      they are under the influence of self-perceived conditions: that is, the
      accessibility of the care, its continuity and the treatment offered by the care
      provider, conditions which, in turn, have a lot in common with the guiding
      principles of local health care. On the other hand, citizens who choose
      passively, because of not being in contact with primary care, have no
      difficulties in being disloyal to the chosen unit when becoming patients. In
      doing so, they also contribute to the fragmentation of local health care. Making
      entirely free choices when it comes to primary care seems to be incompatible with
      local health care. However, choice of care only partly equals the conditions of
      free choice. Choice of care and local health care would thus seem to be
      compatible, in practice, for the majority of patients.

PMID- 22396220
TI  - Neuronal clustering and fasciculation phenotype in Dscam- and Bax-deficient mouse
      retinas.
AB  - Individual types of retinal neurons are distributed to minimize proximity to
      neighboring cells. Many of these same cell types extend dendrites to provide
      coverage of the retinal surface. These two cardinal features of retinal mosaics
      are disrupted, for certain cell types, in mice deficient for the Down syndrome
      cell adhesion molecule, Dscam, exhibiting an aberrant clustering of somata and
      fasciculation of dendrites. The Dscam mutant mouse retina also exhibits excess
      numbers of these same cell types. The present study compared these two features
      in Dscam mutant retinas with the Bax knockout retina, in which excess numbers of
      two of these cell types, the melanopsin-positive retinal ganglion cells (MRGCs)
      and the dopaminergic amacrine cells (DACs), are also present. Whole retinas were
      immunolabeled for both populations, and every labeled soma was plotted. For the
      MRGCs, we found a gene dosage effect for Dscam, with the Dscam+/- retinas showing
      smaller increases in cell number, clustering, and fasciculation. Curiously, Bax-/
      retinas, showing numbers of MRGCs intermediate to those found in the Dscam-/-
      and Dscam+/- retinas, also had clustering and fasciculation phenotypes that were
      intermediate to retinas with those genotypes. DACs, by comparison, showed changes
      in both the Dscam-/- and the Bax-/- retinas that did not correlate with their
      increases in DAC number. The fasciculation phenotype in the Dscam-/- retina was
      particularly prominent despite only modest clustering. These results demonstrate
      that the somal clustering and fasciculation observed in the Dscam mutant retina
      are not unique to Dscam deficiency and are manifested distinctively by different
      retinal cell types.

PMID- 22396222
TI  - Artemisinic acid is a regulator of adipocyte differentiation and C/EBP delta
      expression.
AB  - Adipocyte dysfunction is associated with the development of obesity. In this
      study, artemisinic acid, which was isolated from Artemisia annua L., inhibited
      adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells
      (hAMSCs) and its mechanism of action was determined. The mRNA levels of
      peroxidase proliferation-activated receptor (PPAR) gamma and CCAAT/enhancer
      binding protein (C/EBP) alpha, late adipogenic factors, were reduced by
      artemisinic acid. Moreover, the mRNA levels of the PPAR gamma target genes
      lipoprotein lipase, CD36, adipocyte protein, and liver X receptor were down
      regulated by artemisinic acid. Artemisinic acid reduced expression of the C/EBP
      delta gene without impacting C/EBP beta. In addition, attempts to elucidate a
      possible mechanism underlying the artemisinic acid-mediated effects revealed that
      reduced expression of the C/EBP delta gene was mediated by inhibiting Jun N
      terminal kinase (JNK). Additionally, artemisinic acid also reduced the expression
      of the adipogenesis-associated genes glucose transporter-4 and vascular
      endothelial growth factor. In addition to the interference of artemisinic acid
      with adipogenesis, artemisinic acid significantly attenuated tumor necrosis
      factor-alpha-induced secretion of interleukin-6 by undifferentiated hAMSCs, thus
      influencing insulin resistance and the inflammatory state characterizing obesity.
      Taken together, these findings indicate that inhibiting adipogenic
      differentiation of hAMSCs by artemisinic acid occurs primarily through reduced
      expression of C/EBP delta, which is mediated by the inhibition of JNK and suggest
      that aremisinic acid may be used as a complementary treatment option for obesity
      associated with metabolic syndrome.

PMID- 22396223
TI  - Extensively hydrolysed casein formula supplemented with Lactobacillus rhamnosus
      GG maintains hypoallergenic status: randomised double-blind, placebo-controlled
      crossover trial.
AB  - OBJECTIVE: To evaluate the hypoallergenicity of an extensively hydrolysed (EH)
      casein formula supplemented with Lactobacillus rhamnosus GG (LGG). DESIGN: A
      prospective, randomised, double-blind, placebo-controlled crossover trial.
      SETTING: Two study sites in Italy and The Netherlands. STUDY PARTICIPANTS:
      Children with documented cow's milk allergy were eligible for inclusion in this
      trial. INTERVENTIONS: After a 7-day period of strict avoidance of cow's milk
      protein and other suspected food allergens, participants were tested with an EH
      casein formula with demonstrated hypoallergenicity (control, EHF) and a formula
      of the same composition with LGG added at 10(8) colony-forming units per gram
      powder (EHF-LGG) in randomised order in a double-blind placebo-controlled food
      challenge (DBPCFC). After absence of adverse reactions in the DBPCFC, an open
      challenge was performed with EHF-LGG, followed by a 7-day home feeding period
      with the same formula. MAIN OUTCOME MEASURE: Clinical assessment of any adverse
      reactions to ingestion of study formulae during the DBPCFC. RESULTS: For all
      participants with confirmed cow's milk allergy (n=31), the DBPCFC and open
      challenge were classified as negative. CONCLUSION: The EH casein formula
      supplemented with LGG is hypoallergenic and can be recommended for infants and
      children allergic to cow's milk who require an alternative to formulae containing
      intact cow's milk protein. TRIAL REGISTRATION NUMBER: http://ClinicalTrials.gov
      Identifier: NCT01181297.

PMID- 22396224
TI  - A systematic review with meta-analysis of comprehensive interventions for
      preschool children with autism spectrum disorder (ASD): study protocol.
AB  - INTRODUCTION: The aims of this study are to (1) conduct a systematic review of
      the intervention literature in preschool children with autism spectrum disorder
      (ASD), including types of interventions that are tested and the classification of
      outcome measures used and (2) to undertake a meta-analysis of the studies,
      allowing for the first time the comparison of different approaches to
      intervention using comparative outcomes. There are a number of alternative
      modalities of intervention for preschool children with ASD in use with different
      theoretical background and orientation, each of which tend to use different trial
      designs and outcome measures. There is at this time an urgent need for
      comprehensive systematic review and meta-analyses of intervention studies for
      preschool children with ASD, covering studies of adequate quality across
      different intervention types and measurement methods, with a view to identifying
      the best current evidence for preschool interventions in the disorder. METHODS
      AND ANALYSIS: The authors will perform a systematic review of randomised
      controlled trials for preschool children with ASD aged 0-6 years, along with a
      meta-analysis of qualifying studies across intervention modality. The authors
      will classify the interventions for preschool children with ASD under three
      models: behaviour, multimodal developmental and communication focused. First, the
      authors will perform a systematic review. Then, the authors will conduct a meta
      analysis by comparing the three models with various outcomes using an inverse
      variance method in a random effect model. The authors will synthesise each
      outcome of the studies for the three models using standardised mean differences.
      DISSEMINATION AND ETHICS: This study will identify each intervention's strengths
      and weaknesses. This study may also suggest what kinds of elements future
      intervention programmes for children with ASD should have. The authors strongly
      believe those findings will be able to translated into the clinical practices and
      patients and their family benefits. Review registration: PROSPERO CRD42011001349.

PMID- 22396225
TI  - Hypertension Analysis of stress Reduction using Mindfulness meditatiON and Yoga
      (The HARMONY Study): study protocol of a randomised control trial.
AB  - INTRODUCTION: Hypertension (HTN) is a leading risk factor for preventable
      cardiovascular disease, with over one in five adults affected worldwide.
      Lifestyle modification is a key strategy for the prevention and treatment of HTN.
      Stress has been associated with greater cardiovascular risk, and stress
      management is a recommended intervention for hypertensives. Stress reduction
      through relaxation therapies has been shown to have an effect on human
      physiology, including lowering blood pressure (BP). However, individualised
      behavioural interventions are resource intensive, and group stress management
      approaches have not been validated for reducing HTN. The HARMONY Study is a pilot
      randomised controlled trial designed to determine if mindfulness-based stress
      reduction (MBSR), a standardised group therapy, is an effective intervention for
      lowering BP in stage 1 unmedicated hypertensives. METHODS AND ANALYSIS: Men and
      women unmedicated for HTN with mean daytime ambulatory blood pressure (ABP)
      >=135/85 mm Hg or 24 h ABP >=130/80 mm Hg are included in the study. Subjects are
      randomised to receive MBSR immediately or after a wait-list control period. The
      primary outcome measure is mean awake and 24 h ABP. The primary objective of the
      HARMONY Study is to compare ABP between the treatment and wait-list control arm
      at the 12-week primary assessment period. Results from this study will determine
      if MBSR is an effective intervention for lowering BP in early unmedicated
      hypertensives. ETHICS AND DISSEMINATION: This research project was approved by
      the Sunnybrook Research Ethics Board and the University Health Network Research
      Ethics Board (Toronto, Canada). Planned analyses are in full compliance with the
      principles of the Declaration of Helsinki. Data collection will be completed by
      early spring 2012. Primary and secondary analysis will commence immediately after
      data monitoring is completed; dissemination plans include preparing publications
      for submission during the summer of 2012. TRIAL REGISTRATION NUMBER: This study
      is registered with http://clinicaltrials.gov (NCT00825526).

PMID- 22396226
TI  - A novel MRI-compatible brain ventricle phantom for validation of segmentation and
      volumetry methods.
AB  - PURPOSE: To create a standardized, MRI-compatible, life-sized phantom of the
      brain ventricles to evaluate ventricle segmentation methods using T(1) -weighted
      MRI. An objective phantom is needed to test the many different segmentation
      programs currently used to measure ventricle volumes in patients with Alzheimer's
      disease. MATERIALS AND METHODS: A ventricle model was constructed from
      polycarbonate using a digital mesh of the ventricles created from the 3 Tesla (T)
      MRI of a subject with Alzheimer's disease. The ventricle was placed in a brain
      mold and surrounded with material composed of 2% agar in water, 0.01% NaCl and
      0.0375 mM gadopentetate dimeglumine to match the signal intensity properties of
      brain tissue in 3T T(1) -weighted MRI. The 3T T(1) -weighted images of the
      phantom were acquired and ventricle segmentation software was used to measure
      ventricle volume. RESULTS: The images acquired of the phantom successfully
      replicated in vivo signal intensity differences between the ventricle and
      surrounding tissue in T(1) -weighted images and were robust to segmentation. The
      ventricle volume was quantified to 99% accuracy at 1-mm voxel size. CONCLUSION:
      The phantom represents a simple, realistic and objective method to test the
      accuracy of lateral ventricle segmentation methods and we project it can be
      extended to other anatomical structures.

PMID- 22396228
TI  - A time for herbicide discovery.

PMID- 22396227
TI  - Continuous positive airway pressure for spontaneously breathing premature infants
      with respiratory distress syndrome.
AB  - OBJECTIVE: To analyze the outcome of inborn preterm neonates with respiratory
      distress-syndrome (RDS), using the approach of administering nasal-continuous
      positive-airway-pressure (CPAP) alone and administering surfactant only if they
      require mechanical ventilation (MV). METHODS: All preterm neonates diagnosed as
      RDS from 01-May-2006 to 10-July-2010 were prospectively enrolled for the study at
      a referral centre in India. Nasal-CPAP alone was administered to all
      spontaneously breathing neonates. Surfactant was administered in babies <28 wk
      gestational age if the baby was intubated for resuscitation at birth. For the
      remaining babies, surfactant was administered if the baby required ventilation
      for RDS in first 72 h. The primary outcome assessed was survival to discharge.
      RESULTS: Of the 83 babies with RDS, 33(39.76%) neonates needed MV of which one
      baby was transferred due to non-availability of ventilator. Of the remaining 32
      babies administered MV, 31 were administered surfactant. Fifty (61.24%) babies
      were managed with CPAP alone. Overall, 72/82(87.8%) babies managed at the
      authors' center survived the neonatal period, and 71/82(86.8%) babies were
      discharged to home. Among the neonates who were ventilated, 26/32(81.25%)
      survived the neonatal period, and 25/32(78.12%) were discharged home. Among the
      babies receiving CPAP, 46/50(92%) survived and were discharged to home.
      CONCLUSIONS: Institution of CPAP alone in all spontaneously breathing preterm
      babies with RDS and administration of surfactant to only those needing MV reduces
      the need for intubations and surfactant administration without affecting the
      outcome adversely. Extreme preterms with RDS, however, may be given surfactant if
      they happen to be intubated for resuscitation at birth.

PMID- 22396230
TI  - Therapeutic hypothermia using gel packs for term neonates with hypoxic ischaemic
      encephalopathy in resource-limited settings: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy of therapeutic hypothermia (TH) using gel
      packs in reducing mortality and morbidity in term neonates with HIE and study the
      associated problems with TH. METHODS: Hypoxic ischaemic encephalopathy babies
      were randomized into TH and control group. Babies in TH group were cooled for
      first 72 h of birth using cloth covered cooling gel packs to maintain target
      rectal temperature of 33-34 degrees C. Infants were followed up to 6 months and
      were assessed using Baroda Developmental Screening Test. RESULTS: There were no
      significant differences in baseline parameters. TH group showed significant
      reduction in the combined rate of death or developmental delay at 6 months of age
      by 21% (8.1% in the TH group vs. 29% in the control, RR 0.28, 95% CI: 0.11-0.70;
      p = 0.003). CONCLUSIONS: TH using gel packs reduces the risk of death or
      developmental delay at 6 months of age in infants with HIE.

PMID- 22396229
TI  - Fluorescent proteins for FRET microscopy: monitoring protein interactions in
      living cells.
AB  - The discovery and engineering of novel fluorescent proteins (FPs) from diverse
      organisms is yielding fluorophores with exceptional characteristics for live-cell
      imaging. In particular, the development of FPs for fluorescence (or Forster)
      resonance energy transfer (FRET) microscopy is providing important tools for
      monitoring dynamic protein interactions inside living cells. The increased
      interest in FRET microscopy has driven the development of many different methods
      to measure FRET. However, the interpretation of FRET measurements is complicated
      by several factors including the high fluorescence background, the potential for
      photoconversion artifacts and the relatively low dynamic range afforded by this
      technique. Here, we describe the advantages and disadvantages of four methods
      commonly used in FRET microscopy. We then discuss the selection of FPs for the
      different FRET methods, identifying the most useful FP candidates for FRET
      microscopy. The recent success in expanding the FP color palette offers the
      opportunity to explore new FRET pairs.

PMID- 22396231
TI  - Electrophysiological characterization of the polyspecific organic cation
      transporter plasma membrane monoamine transporter.
AB  - Plasma membrane monoamine transporter (PMAT) is a polyspecific organic cation
      (OC) transporter that transports a variety of endogenous biogenic amines and
      xenobiotic cations. Previous radiotracer uptake studies showed that PMAT-mediated
      OC transport is sensitive to changes in membrane potential and extracellular pH,
      but the precise role of membrane potential and protons on PMAT-mediated OC
      transport is unknown. Here, we characterized the electrophysiological properties
      of PMAT in Xenopus laevis oocytes using a two-microelectrode voltage-clamp
      approach. PMAT-mediated histamine uptake is associated with inward currents under
      voltage-clamp conditions, and the currents increased in magnitude as the holding
      membrane potential became more negative. A similar effect was also observed for
      another cation, nicotine. Substrate-induced currents were largely independent of
      Na+ but showed strong dependence on membrane potential and pH of the perfusate.
      Detailed kinetic analysis of histamine uptake revealed that the energizing effect
      of membrane potentials on PMAT transport is mainly due to an augmentation of Imax
      with little effect on K0.5. At most holding membrane potentials, Imax at pH 6.0
      is approximately 3- to 4-fold higher than that at pH 7.5, whereas K0.5 is not
      dependent on pH. Together, these data unequivocally demonstrate PMAT as an
      electrogenic transporter and establish the physiological inside-negative membrane
      potential as a driving force for PMAT-mediated OC transport. The important role
      of membrane potential and pH in modulating the transport activity of PMAT toward
      OCs suggests that the in vivo activity of PMAT could be regulated by
      pathophysiological processes that alter physiological pH or membrane potential.

PMID- 22396233
TI  - [Safe insertion of hemodialysis catheter by ultrasound-guidance].

PMID- 22396234
TI  - [Antiretroviral HIV therapy protects the non-infected partner].

PMID- 22396235
TI  - [Type 2 diabetes mellitus and depressive symptoms: what is the cause of what? A
      systematic literature review].
AB  - BACKGROUND: Diabetes mellitus type 2 and depressive symptoms are statistically
      associated. The question is if one of the two diseases is causal for the other.
      METHODS: Systematic review using Medline and searching for prospective controlled
      population based observational studies and meta-analysis in English or German
      language. RESULTS: Patients with type 2 diabetes have a higher incidence of
      depressive symptoms - compared to patients having no diabetes. And patients with
      depressive symptoms have a higher incidence of type 2 diabetes; however the
      findings for the first relation are only weak. DISCUSSION: Knowing about this -
      even causal - co-morbidity is important in care, including a routine diagnostic
      approach to find out if the other disease is also present.

PMID- 22396236
TI  - [Ulcerating tumor of the esophagus as a primary manifestation of extrapulmonary
      tuberculosis].
AB  - HISTORY AND ADMISSION FINDINGS: The patient, a 36-year-old man from Somalia, who
      had moved to Germany a year before, was referred for a diagnostic work-up of an
      ulcerating tumour. He suffered from thoracic tightness for the last weeks albeit
      without any further symptoms. There were no pre-existing illnesses. No further
      pathological signs were found during a preliminary physical examination.
      INVESTIGATIONS: After ruling out any malignancies by means of an analysis of
      biopsy samples, further differential diagnostic measures were undertaken. Besides
      mechanical and chemical factors, an infectious genesis of the esophageal lesion
      was considered and investigated further through histological,
      immunohistochemical, laboratory and microbiological tests. DIAGNOSIS, TREATMENT
      AND COURSE: Mycobacterium tuberculosis was detected in cultures sampled from
      biopsy material. This strain turned out to be responsive to medical treatment.
      Further diagnostics regarding a potential primary pulmonary tuberculosis were
      negative. Histological analysis of a liver biopsy confirmed noncaseating
      epithelioid cellular granuloma as typically seen in granulomatous hepatitis
      without any direct evidence of mycobacteria. Thus, tuberculosis of the liver
      appeared most likely considering the differential diagnosis of a granulomatous
      hepatitis. The patient underwent standard treatment using antituberculous drugs
      over six months. Endoscopic control after two months showed a significant
      reduction of the ulcerating lesion. CONCLUSION: Ulcerating tumors of the
      esophagus are primarily classified as potential malignancies. Crohn's disease is
      an important differential diagnosis. Apart from mechanical and chemical causes,
      infectious diseases should be taken into consideration. However, tuberculosis is
      one of the most relevant differential diagnoses, particularly in patients
      immigrating from TB-prone countries, pre-existing immune deficiency or
      environmentally induced elevated infection risk.

PMID- 22396237
TI  - [86-year-old patient with left thoracic, breathing-dependent pain].

PMID- 22396238
TI  - [Vascular complications after endovascular interventions].

PMID- 22396239
TI  - [Use of alternative and complementary therapies in clinical practice using
      multiple sclerosis as an example].
AB  - The discrimination between complementary and alternative medicine / therapies
      (CAM) at one hand and conventional treatment at the other hand is vague and still
      under controversial discussion. Furthermore, most CAM lacks evidence for
      effectiveness, and in some cases for some CAM potential health risks or high
      costs are reported. The countless methods and treatments of CAM have been
      categorized by National Center of Complementary and Alternative Medicine into
      five groups: alternative medical systems, mind-body-interventions, biologically
      based therapies, manipulating and body-based therapies, and energy therapies. CAM
      are known and used cross-cultural and are applied to a variety of different
      medical conditions. Patients report manifold reasons for using CAM, which will be
      discussed on the sample of patients with multiple sclerosis. It was shown often,
      that patients use CAM without informing their attending physician. Applying CAM
      is essentially affected by wishes of patients for active therapy attendance,
      dissatisfaction with conventional treatment and negative patient-physician
      relation. Therefore, the attending physician should be well informed about CAM
      and should be open to talk about CAM to advice the patient to his best knowledge.
      Otherwise the patient may move synchronously or serial into two separated therapy
      settings without informing his attending physician, which may cause health or
      financial damage.

PMID- 22396240
TI  - Miscibility studies of indomethacin and Eudragit(r) E PO by thermal, rheological,
      and spectroscopic analysis.
AB  - The objective of this study is to understand the underlying mechanisms
      responsible for the superior stability of indomethacin (INM)-Eudragit(r) E PO (E
      PO) system by exploring the miscibility and intermolecular interactions through
      the combination of thermal, rheological, and spectroscopic analysis. The zero
      shear-rate viscosity drops monotonically with the increase of INM concentration
      at 145  degrees C, suggesting that E PO and INM form a solution and the small
      molecular drug acts as a plasticizer. Flow activation energy was calculated from
      the viscosity data at different temperature. The glass transition temperature
      (T(g)) of the mixture at different composition was determined using differential
      scanning calorimetry. The T(g) and flow activation energy peak at the INM
      concentration around 60%-70%. Fourier transform infrared analysis provided direct
      evidence for the intermolecular ionic interactions, which may disrupt the dimer
      formation of amorphous INM. The study explained the superior stability of INM-E
      PO mixtures, and demonstrated that a combination of thermal, rheological, and
      spectroscopic technologies can help us to obtain a full picture of the drug
      polymer interactions and to determine the formulation and processing conditions.

PMID- 22396241
TI  - Metabolic syndrome decreases tissue perfusion and induces glandular hyperplasia
      in the fructose-fed rat prostate.
AB  - AIMS: The effects of metabolic syndrome on the prostate blood perfusion and
      histological structure were studied using fructose-fed rats (FR). METHODS: Age
      matched male Wistar rats were divided into two groups: group I, normal control
      rats and group II, 9-week FR. Animal body weight, blood pressure, and serum
      metabolic parameters were monitored. With the rats under anesthesia, prostatic
      blood flow volume and flow velocity were measured by laser Doppler flowmetry. The
      prostate was then removed for histological examination and morphometric study.
      RESULTS: The 9-week FR showed significant increases in body weight, blood
      pressure, plasma glucose, insulin, and triglyceride levels. The blood flow volume
      (345.8 +/- 20.57 ml/min/100 g vs. 440.4 +/- 35.57 ml/min/100 g of tissue, P <
      0.05 for n = 8) and flow rate (29.4 +/- 1.25 units vs. 40.9 +/- 2.65 units, P <
      0.05 for n = 8) in the FR ventral prostate were significantly decreased when
      compared to controls. Structurally, the FR prostate weight was significantly
      higher than that of the controls (612.4 +/- 16.9 mg vs. 427.3 +/- 6.5 mg, P <
      0.05 for n = 8). Prostate histology showed glandular hyperplasia while
      morphometry showed increased stromal component in the FR. CONCLUSIONS: Metabolic
      syndrome in the FR decreases prostatic perfusion and induces prostatic glandular
      hyperplasia. The findings suggest that chronic ischemia may be a link between
      metabolic syndrome and prostatic enlargement.

PMID- 22396242
TI  - F-18 FDG PET/CT imaging of solitary liver Langerhans cell histiocytosis:
      preliminary findings.
AB  - Langerhans cell histiocytosis (LCH) is a disorder of clonal proliferation of
      Langerhans-type cells. The imaging findings of LCH are not specific. A 27-year
      old woman was admitted to our hospital because of liver enzyme elevation without
      other hepatic signs. Radiological studies were originally interpreted as possible
      metastatic disease to the liver. Fluorine-18 fluorodeoxyglucose positron emission
      tomography/computed tomography (F-18 FDG PET/CT) images demonstrated a diffuse
      pattern of nodules in the liver with hypermetabolic activity. LCH was diagnosed
      histopathologically with an ultrasound-guided liver biopsy. This case illustrates
      the importance of considering proliferative/benign conditions of the liver when
      interpreting PET/CT. Failure to do so could result in patient mismanagement. 

PMID- 22396243
TI  - Lead time TTO: leading to better health state valuations?
AB  - Preference elicitation tasks for better than dead (BTD) and worse than dead (WTD)
      health states vary in the conventional time trade-off (TTO) procedure, casting
      doubt on uniformity of scale. 'Lead time TTO' (LT-TTO) was recently introduced to
      overcome the problem. We tested different specifications of LT-TTO in comparison
      with TTO in a within-subject design. We elicited preferences for six health
      states and employed an intertemporal ranking task as a benchmark to test the
      validity of the two methods. We also tested constant proportional trade-offs
      (CPTO), while correcting for discounting, and the effect of extending the lead
      time if a health state is considered substantially WTD. LT-TTO produced lower
      values for BTD states and higher values for WTD states. The validity of CPTO
      varied across tasks, but it was higher for LT-TTO than for TTO. Results indicate
      that the ratio of lead time to disease time has a greater impact on results than
      the total duration of the time frame. The intertemporal ranking task could not
      discriminate between TTO and LT-TTO.

PMID- 22396244
TI  - Persistence of pyrazosulfuron in rice-field and laboratory soil under Indian
      tropical conditions.
AB  - BACKGROUND: Pyrazosulfuron ethyl, a new rice herbicide belonging to the
      sulfonylurea group, has recently been registered in India for weed control in
      rice crops. Many field experiments revealed the bioefficacy of this herbicide;
      however, no information is available on the persistence of this herbicide in
      paddy soil under Indian tropical conditions. Therefore, a field experiment was
      undertaken to investigate the fate of pyrazosulfuron ethyl in soil and water of
      rice fields. Persistence studies were also carried out under laboratory
      conditions in sterile and non-sterile soil to evaluate the microbial contribution
      to degradation. RESULTS: High-performance liquid chromatography (HPLC) of
      pyrazosulfuron ethyl gave a single sharp peak at 3.41 min. The instrument
      detection limit (IDL) for pyrazosulfuron ethyl by HPLC was 0.1 ug mL(-1) , with a
      sensitivity of 2 ng. The estimated method detection limit (EMDL) was 0.001 ug mL(
      1) and 0.002 ug g(-1) for water and soil respectively. Two applications at an
      interval of 10 days gave good weed control. The herbicide residues dissipated
      faster in water than in soil. In the present study, with a field-soil pH of 8.2
      and an organic matter content of 0.5%, the pyrazosulfuron ethyl residues
      dissipated with a half-life of 5.4 and 0.9 days in soil and water respectively.
      Dissipation followed first-order kinetics. Under laboratory conditions,
      degradation of pyrazosulfuron ethyl was faster in non-sterile soil (t(1/2) = 9.7
      days) than in sterile soil (t(1/2) = 16.9 days). CONCLUSION: Pyrazosulfuron ethyl
      is a short-lived molecule, and it dissipated rapidly in field soil and water. The
      faster degradation of pyrazosulfuron in non-sterile soil than in sterile soil
      indicated microbial degradation of this herbicide.

PMID- 22396245
TI  - The effect of exercise on affective and self-efficacy responses in older and
      younger women.
AB  - BACKGROUND: This study examined the self-efficacy and affective responses to an
      acute exercise bout in sedentary older and younger women to determine whether
      aging has an effect on affective states. METHODS: Twenty-five sedentary younger
      (mean age = 19.9 yrs) and 25 older (mean age = 55.7 yrs) women completed an acute
      bout of exercise. Affective responses were measured before, during, and
      immediately following exercise. Self-efficacy responses were measured before and
      immediately following exercise. RESULTS: Positive engagement, revitalization,
      tranquility, Felt Arousal and Feeling Scale responses, and self-efficacy were all
      higher immediately following compared with before or during exercise for both
      groups of women. In addition, older women experienced higher overall positive
      engagement and lower physical exhaustion compared with younger women as well as
      higher tranquility and Feeling Scale responses immediately following exercise.
      CONCLUSIONS: This investigation found that an acute bout of moderate-intensity
      exercise produced more positive and fewer negative affective states in both
      younger and older women.

PMID- 22396246
TI  - Slicing embryos gently with laser light sheets.
AB  - Light sheet microscopy is an easy to implement and extremely powerful alternative
      to established fluorescence imaging techniques such as laser scanning confocal,
      multi-photon and spinning disk microscopy. By illuminating the sample only with a
      thin slice of light, photo-bleaching is reduced to a minimum, making light sheet
      microscopy ideal for non-destructive imaging of fragile samples over extended
      periods of time. Millimeter-sized samples can be imaged rapidly with high
      resolution and high depth penetration. A large variety of instruments have been
      developed and optimized for a number of different samples: Bessel beams form thin
      light sheets for single cells, and selective plane illumination microscopy (SPIM)
      offers multi-view acquisition to image entire embryos with isotropic resolution.
      This review explains how light sheet microscopy involves a conceptually new
      microscope design and how it changes modern imaging in biology.

PMID- 22396247
TI  - Depression, anxiety, and risk factor control in patients after hospitalization
      for coronary heart disease: the EUROASPIRE III Study.
AB  - OBJECTIVE: To assess in coronary heart disease (CHD) patients: (1) differences in
      the prevalence of depression and anxiety between samples selected from 22
      countries; (2) the association of depression and anxiety with age, education,
      diagnostic category, favourable behaviours, use of cardioprotective drugs, and
      reaching the secondary prevention treatment targets. DESIGN: Cross-sectional
      study. METHODS: The study group consisted of 8580 patients from 22 European
      countries examined at least 6 months after hospitalization due to CHD. Depression
      and anxiety were assessed using Hospital Anxiety and Depression Scale (HADS).
      RESULTS: Prevalence of depression (HADS depression score >= 8) varied from 8.2%
      to 35.7% in men and from 10.3% to 62.5% in women. Prevalence of anxiety (HADS
      anxiety score >= 8) varied from 12.0% to 41.8% in men and from 21.5% to 63.7% in
      women. Older age, female sex, low education, and no history of invasive treatment
      were associated with more frequent depression and anxiety. Depression and anxiety
      were associated with less frequent modification of lifestyle. Depression was
      related with body mass index, waist circumference, fasting glucose, and more
      frequent self-reported diabetes but not with reaching the treatment targets for
      blood pressure and lipids. CONCLUSIONS: High prevalence of depression and anxiety
      in CHD patients, and relation with less frequent lifestyle modification, call to
      integrate methods of identification and minimizing unfavourable effects of
      depression and anxiety into the cardiac rehabilitation and prevention programmes.

PMID- 22396249
TI  - Alcohol consumption in mild cognitive impairment and dementia: harmful or
      neuroprotective?
AB  - OBJECTIVE: In several longitudinal studies, light-to-moderate drinking of
      alcoholic beverages has been proposed as being protective against the development
      of age-related changes in cognitive function, predementia syndromes, and
      cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin
      (vascular dementia). However, contrasting findings also exist. METHOD: The
      English literature published in this area before September 2011 was evaluated,
      and information relating to the various factors that may impact upon the
      relationship between alcohol consumption and dementia or predementia syndromes is
      presented in the succeeding texts. RESULTS: Light-to-moderate alcohol consumption
      may be associated with a reduced risk of incident overall dementia and AD;
      however, protective benefits afforded to vascular dementia, cognitive decline,
      and predementia syndromes are less clear. The equivocal findings may relate to
      many of the studies being limited to cross-sectional designs, restrictions by age
      or gender, or incomplete ascertainment. Different outcomes, beverages, drinking
      patterns, and study follow-up periods or possible interactions with other
      lifestyle-related (e.g., smoking) or genetic factors (e.g., apolipoprotein E gene
      variation) may all contribute to the variability of findings. CONCLUSION:
      Protective effects of moderate alcohol consumption against cognitive decline are
      suggested to be more likely in the absence of the AD-associated apolipoprotein E
      epsilon4 allele and where wine is the beverage. At present, there is no
      indication that light-to-moderate alcohol drinking would be harmful to cognition
      and dementia, and attempts to define what might be deemed beneficial levels of
      alcohol intake in terms of cognitive performance would be highly problematic and
      contentious.

PMID- 22396248
TI  - Beyond resolutions? A randomized controlled trial of a self-regulation lifestyle
      programme for post-cardiac rehabilitation patients.
AB  - BACKGROUND: As lifestyle adherence and risk factor management following
      completion of cardiac rehabilitation (CR) have been shown to be problematic, we
      developed a brief self-regulation lifestyle programme for post-CR patients.
      DESIGN: Randomized-controlled trial. METHODS: Following completion of CR 210
      patients were randomized to receive either a lifestyle maintenance programme (n =
      112) or standard care (n = 98). The programme was based on self-regulation
      principles and consisted of a motivational interview, seven group sessions, and
      home assignments. Risk factors and health behaviours were assessed at baseline
      (end of CR) and 6 months thereafter. RESULTS: ANCOVAs showed a significant effect
      of the lifestyle programme after 6 months on blood pressure, waist circumference,
      and exercise behaviour. CONCLUSION: This trial indicates that a relatively brief
      intervention based on self-regulation theory is capable of instigating and
      maintaining beneficial changes in lifestyle and risk factors after CR.

PMID- 22396250
TI  - Obstruction enhances rho-kinase pathway and diminishes protein kinase C pathway
      in carbachol-induced calcium sensitization in contraction of alpha-toxin
      permeabilized guinea pig detrusor smooth muscle.
AB  - AIMS: We investigated the relative important role of rho kinase (ROK) and protein
      kinase C (PKC) pathways in carbachol (CCh)-induced Ca(2+) sensitization in alpha
      toxin permeabilized Guinea pig detrusor smooth muscle (DSM) following bladder
      outlet obstruction (BOO). METHODS: Bladder outlet obstruction was created by
      placement of a silver jeweler's jump rings loosely round the urethro-vesical
      junction of Guinea pigs. Sham operated Guinea pig underwent a similar protocol
      without application of the ring and served as control. alpha-Toxin permeabilized
      DSM strips from control Guinea pigs and those subjected to 6-8 weeks of BOO were
      mounted horizontally for isometric force recording in 100 ul relaxing solution on
      perspex block. The effect of ROK inhibitor (Y-27632) and PKC inhibitor (GF
      109203X) on CCh-induced Ca(2+) sensitization was studied during sustained
      contraction. Permeabilized DSM strips were also stimulated by cumulative increase
      of Ca(2+) concentration compared to that in control in the presence and in the
      absence of sensitization-induced PKC activator, phorbol 12,13-dibutyrate.
      RESULTS: Ca(2+) sensitization-induced by CCh was greater in BOO compared to
      controls. This muscarinic agonist-induced Ca(2+) sensitization was inhibited by Y
      27632 or GF-109203X. The inhibitory effect of Y-27632 (5 uM) was greater while
      the inhibitory effect of GF-109203X (5 uM) was smaller in BOO compared to that in
      controls. Phorbol 12,13-dibutyrate (1 uM) markedly increased Ca(2+) sensitivity
      in controls but not in BOO. CONCLUSIONS: Our findings provide the first evidence
      that BOO enhances the ROK pathway and diminishes the PKC pathway in CCh-induced
      Ca(2+) sensitization in contraction of permeabilized Guinea pig DSM and suggest
      that inhibitors of ROK might potentially relieve bladder dysfunction related to
      BOO.

PMID- 22396251
TI  - Endoscopic removal of migrated esophageal stent--the "grasper and pusher" method.

PMID- 22396252
TI  - Incidental removal of distal common bile duct adenoma after plastic stent
      placement.

PMID- 22396253
TI  - Salivary gland choristoma in large bowel.

PMID- 22396254
TI  - Endoscopic mucosal resection of inflammatory fibroid polyp in the transverse
      colon.

PMID- 22396255
TI  - Pancreaticobiliary obstruction following duodenal stent placement.

PMID- 22396256
TI  - Thoracic spine osteophyte causing dysphagia.

PMID- 22396257
TI  - Jejunal pyogenic granuloma diagnosed and treated with spiral enteroscopy.

PMID- 22396258
TI  - A pseudosarcomatous lesion resembling a malignant tumor of the esophagocardiac
      junction, diagnosed by a total biopsy with endoscopic surgery.

PMID- 22396259
TI  - Exfoliative esophagitis and esophageal ulcer induced by dabigatran.

PMID- 22396260
TI  - Successful endoscopic submucosal dissection for triple sporadic nonampullary
      duodenal adenomas using a "push and peel off" technique.

PMID- 22396261
TI  - Duodenal perforation due to toothpick perforation, an uncommon cause of chronic
      abdominal pain.

PMID- 22396262
TI  - Toothpick impaction with localized sigmoid perforation: successful double-balloon
      enteroscopic management.

PMID- 22396263
TI  - Endoscopic findings of small-intestinal Epstein-Barr virus-associated T-cell
      lymphoproliferative disorder.

PMID- 22396265
TI  - Duodenal bleeding caused by pancreatic tuberculosis in a patient with AIDS and
      disseminated tuberculosis.

PMID- 22396264
TI  - Rectal perforation due to benign stricture caused by rectal burns associated with
      hot coffee enemas.

PMID- 22396266
TI  - Over-the-scope clip used to control bleeding from a duodenal ulcer.

PMID- 22396268
TI  - Endoscopic submucosal dissection with a ligation device for the     treatment of
      rectal carcinoid tumor.

PMID- 22396267
TI  - Percutaneous endoscopic gastrostomy tube placement complicated by a gastric
      pseudoaneurysm and recurrent hemorrhage.

PMID- 22396269
TI  - Gastric band cutter to remove a migrated gastric band.

PMID- 22396270
TI  - Colonic telangiectasias in progressive systemic sclerosis.

PMID- 22396271
TI  - Cat scratch esophagus.

PMID- 22396272
TI  - Acute pancreatitis evoked by small-cell lung carcinoma metastases and detected by
      endoscopic ultrasound.

PMID- 22396273
TI  - Hypertrophic gastric folds caused by metastatic prostate adenocarcinoma.

PMID- 22396274
TI  - Endoscopic vacuum-assisted therapy of infected pancreatic pseudocyst using a
      coated sponge.

PMID- 22396275
TI  - Stent migration after stent-in-stent technique using a biodegradable stent.

PMID- 22396276
TI  - PEG tube placement in morbidly obese patients.

PMID- 22396277
TI  - A rare cause of ischemic proctosigmoiditis: idiopathic myointimal hyperplasia of
      mesenteric veins.

PMID- 22396278
TI  - Menetrier disease with antrum polyposis and gastritis cystica profunda.

PMID- 22396279
TI  - ERCP in Roux-en-Y gastric bypass: creation of an antegrade gastrogastric conduit
      using a fully covered metal esophageal stent.

PMID- 22396280
TI  - Balloon-catheter-assisted endoscopic snare resection for     choledochocele using
      a single-channel duodenoscope.

PMID- 22396281
TI  - Endoscopic appearance of sclerosing mesenteritis in the colon.

PMID- 22396282
TI  - Capsule-endoscopic findings in immunoproliferative small-intestinal disease.

PMID- 22396283
TI  - An African American man with dysphagia: a unique initial presentation of
      sarcoidosis.

PMID- 22396284
TI  - Pancreatic rupture during childbirth treated successfully by endoscopic drainage.

PMID- 22396285
TI  - Autoimmune hepatitis diagnosed by endoscopic ultrasound-guided liver biopsy using
      a new 19-gauge histology needle.

PMID- 22396286
TI  - Endoscopic incision of a rectal anastomotic fistula wall following pancolectomy
      with ileorectal anastomosis.

PMID- 22396287
TI  - Eosinophilic esophagitis with pseudodiverticulosis: a rare coincidence.

PMID- 22396288
TI  - Mast cell activation syndrome (MCAS) diagnosed using double-balloon enteroscopy.

PMID- 22396289
TI  - Treatment of a refractory biliary stricture after living donor liver
      transplantation, with a short fully covered metal stent with a long string.

PMID- 22396290
TI  - Osseous metaplasia of the colon in an ulcerative proctosigmoiditis.

PMID- 22396291
TI  - Fluorescein-guided confocal laser endomicroscopy for the detection of ipilimumab
      induced colitis.

PMID- 22396292
TI  - Closure of a persistent esophagopleural fistula assisted by a novel endoscopic
      suturing system.

PMID- 22396293
TI  - Confocal laser endomicroscopy for characterization of Crohn's disease-associated
      duodenitis.

PMID- 22396294
TI  - Osseous metaplasia in a gastric adenomatous polyp.

PMID- 22396295
TI  - Renal cell carcinoma with direct colonic invasion.

PMID- 22396296
TI  - Biliary intraductal papillary mucinous neoplasm visualized intralesionally
      through a fistula with the duodenal bulb.

PMID- 22396297
TI  - Loop observe and snare technique for endoscopic resection of a gastric
      inflammatory fibroid polyp.

PMID- 22396298
TI  - Colonic gallstone ileus treated with radiologically guided extracorporeal shock
      wave lithotripsy followed by endoscopic extraction.

PMID- 22396299
TI  - Endoscopic band ligation to create an omental patch for closure of a colonic
      perforation.

PMID- 22396301
TI  - Abstracts of the British Psychosocial 2012 Conference. January 19-20, 2012.
      Leeds, United Kingdom.

PMID- 22396302
TI  - Beyond the connectome: how neuromodulators shape neural circuits.
AB  - Powerful ultrastructural tools are providing new insights into neuronal circuits,
      revealing a wealth of anatomically-defined synaptic connections. These wiring
      diagrams are incomplete, however, because functional connectivity is actively
      shaped by neuromodulators that modify neuronal dynamics, excitability, and
      synaptic function. Studies of defined neural circuits in crustaceans, C. elegans,
      Drosophila, and the vertebrate retina have revealed the ability of modulators and
      sensory context to reconfigure information processing by changing the composition
      and activity of functional circuits. Each ultrastructural connectivity map
      encodes multiple circuits, some of which are active and some of which are latent
      at any given time.

PMID- 22396303
TI  - Parental ADHD affects parent and child outcomes of parental friendship coaching.

PMID- 22396304
TI  - Pharmacokinetic evaluation of intranasally administered vinyl polymer-coated
      lorazepam microparticles in rabbits.
AB  - The intranasal (IN) administration of lorazepam is desirable in order to maximize
      speed of onset and minimise carry-over sedation; however, this benzodiazepine is
      prone to chemical hydrolysis and poor airway retention, and thus, innovative
      epithelial presentation is required. The aim of this study was to understand how
      the in situ self-assembly of a mucoretentive delivery system, formed by the
      dissolution of vinyl polymer-coated microparticles in the nasal mucosa, would
      influence lorazepam pharmacokinetics (PK). IN administration of the uncoated
      lorazepam powder (particle size, 6.7 +/- 0.1 MUm) generated a biphasic PK
      profile, which was indicative of sequential intranasal and oral absorption (n =
      6; dose, 5 mg/kg). Coating the drug with the vinyl polymer, MP1 (9.9 +/- 0.5 MUm
      with 38.8 +/- 14.0%, w/w lorazepam) and MP2 (10.7 +/- 0.1 MUm with 47.0 +/- 1.0%,
      w/w lorazepam), allowed rapid systemic absorption (MP1, T (max) 14.2 +/- 4.9 min;
      MP2, T (max) 9.3 +/- 3.8 min) in rabbits and modified the PK profiles in a manner
      that suggested successful nasal retention. The poly(vinyl pyrrolidone)-rich MP2
      system provided the best comparative bioavailability, it prolonged the early
      phase nasal drug absorption and minimised drug mucociliary clearance, which
      correlated well with the intermolecular hydrogen-bond-driven vinyl polymer
      interactions observed in vitro.

PMID- 22396305
TI  - Scale-up of cell culture bioreactors using biomechatronic design.
AB  - Scale-up of cell culture bioreactors is a challenging engineering work that
      requires wide competence in cell biology, mechanical engineering and bioprocess
      design. In this article, a new approach for cell culture bioreactor scale-up is
      suggested that is based on biomechatronic design methodology. The approach
      differs from traditional biochemical engineering methodology by applying a
      sequential design procedure where the needs of the users and alternative design
      solutions are systematically analysed. The procedure is based on the biological
      and technical functions of the scaled-up bioreactor that are derived in
      functional maps, concept generation charts and scoring and interaction matrices.
      Basic reactor engineering properties, such as mass and heat transfer and kinetics
      are integrated in the procedure. The methodology results in the generation of
      alternative design solutions that are thoroughly ranked with help of the user
      needs. Examples from monoclonal antibodies and recombinant protein production
      illuminate the steps of the procedure. The methodology provides engineering teams
      with additional tools that can significantly facilitate the design of new
      production methods for cell culture processes.

PMID- 22396306
TI  - Use of natural pyrethrum to control the red swamp crayfish Procambarus clarkii in
      a rural district of Italy.
AB  - BACKGROUND: The crayfish Procambarus clarkii inflicts severe ecological and
      economic damages in Europe. To develop an efficient method for its control, four
      experiments were carried out to assess the impact of natural pyrethrum (i.e.
      Pyblast) on crayfish: (1) the 24 h LC(100) and LC(50) were quantified on
      crayfish; (2) the breakdown time of the 24 h LC(100) was assessed using Daphnia
      magna as a bioindicator; the effects of 24 h LC(100) on crayfish were
      investigated by applying the biocide into burrows (3) and in a drainage channel
      (4). RESULTS: Pyblast concentrations of 0.05 and 0.02 mg L(-1) corresponded to 24
      h LC(100) and LC(50) respectively. The concentration of 0.05 mg L(-1) broke down
      after 72 h, whereas 0.02 mg L(-1) did not cause any significant mortality in D.
      magna after 24 h. However, 0.05 mg L(-1) had no effect on crayfish when
      introduced into the burrows, but led to a mortality of 95% when applied in the
      water. CONCLUSION: Experimental evidence is provided for the efficacy of Pyblast
      to control invasive crayfish. Obviously, before its use on a large scale, further
      studies are needed to find a concentration that will achieve the target 100%
      mortality with the shortest recovery time of the environment.

PMID- 22396307
TI  - Association of cerebral small vessel disease with delusions in patients with
      Alzheimer's disease.
AB  - BACKGROUND: Cerebral small vessel disease (SVD) is frequently observed in
      patients with Alzheimer's disease (AD). However, the association between SVD and
      clinical symptoms exhibited by patients with AD remains unclear. This study
      examined the association of SVD as observed on magnetic resonance imaging (MRI)
      with behavioural and psychological symptoms of dementia and cognitive function of
      patients with probable AD. METHODS: A total of 163 consecutive patients (55 men,
      108 women) with probable AD were included in this cross-sectional study of a
      prospective cohort. Patients were divided into two groups based on the presence
      or absence of cerebral SVD [white matter hyperintensities (WMH) grade 0/1
      (Fazekas scale) and no lacunes: SVD absent, WMH grade 2/3 (Fazekas scale) or the
      number of lacunes >=1: SVD present]. Cognitive functions were assessed using the
      Mini mental state examination, word recall and recognition subtests in the
      Alzheimer's Disease Assessment Scale-Cognitive Subscale, as well as the letter
      fluency task and the category fluency task. Psychiatric symptoms were rated
      according to Neuropsychiatric Inventory. RESULTS: Patients with probable AD with
      cerebral SVD had significantly more delusions and depression than those without
      SVD. No significant differences were observed in other neuropsychiatric symptoms,
      MMSE or word recall and recognition tests between both groups. CONCLUSIONS: Our
      results suggest that cerebral SVD observed on MRI of patients with AD is
      associated with delusions and depression.

PMID- 22396308
TI  - Moving towards a comprehensive assessment of lower urinary tract symptoms (LUTS).
AB  - AIMS: To evaluate the utility of the International Prostate Symptom Score (IPSS)
      and the LUTS Tool when assessing lower urinary tract symptoms (LUTS). Secondary
      objectives were to examine associations of LUTS and treatment seeking. METHODS:
      Analyses were performed using EpiLUTS data, a population-based, cross-sectional,
      Internet survey of men and women (aged >=40) in Sweden, UK, and US with a sample
      of 30,000 participants. Participants completed the IPSS and the LUTS Tool.
      Prevalence rates of symptoms captured by the LUTS Tool were compared using IPSS
      summary scores: 0, 1-7, 8-19, and >=20. LUTS Tool subscale scores were
      calculated. Pearson correlations between the LUTS Tool symptoms and subscales and
      IPSS symptoms were performed. Logistic regressions evaluated the associations of
      IPSS scores and LUTS Tool subscales with treatment seeking for LUTS. RESULTS: The
      IPSS did not assess some symptoms (i.e., incontinence) for which there was a high
      prevalence among participants. Correlations between the 7 symptoms assessed by
      the IPSS and LUTS Tool were moderate to high ranging between 0.37 (nocturia
      women) and 0.77 (weak stream men), indicating concordance. While the LUTS Tool
      subscales and the total IPSS score were all significantly associated with
      treatment seeking, the LUTS Tool OAB subscale in men and Voiding subscale in
      women most strongly predicted treatment seeking. CONCLUSION: LUTS that are
      excluded from the IPSS, most notably incontinence, were prevalent even among
      mildly symptomatic participants. Since storage symptoms appear to drive treatment
      seeking, identifying, and treating these symptoms is essential when caring for
      patients with LUTS.

PMID- 22396311
TI  - An in vivo study on the effect of scaffold geometry and growth factor release on
      the healing of bone defects.
AB  - The hypothesis of this study was that the extent of bone regeneration could be
      enhanced by using scaffolds with appropriate geometry, and that such an effect
      could be further increased by mimicking the natural timing of appearance of bone
      morphogenetic proteins BMP-2 and BMP-7 after fracture. Bioplotted poly(epsilon
      caprolactone) (PCL) disks with four different fibre organizations were used to
      study the effect of 3D scaffold architecture on the healing of bone defects in a
      rat pelvis model. Moreover, one PCL construct was further modified by introducing
      a nanoparticulate sequential BMP-2/BMP-7 delivery system into this scaffold.
      Scaffolds and functionalized construct along with free nanocapsules were
      implanted using a rat iliac crest defect model. Six weeks post-implantation, the
      defects were evaluated by CT scan and histology. Analysis revealed that the basic
      architecture, having the highest pore volume for tissue ingrowth, presented the
      highest bone formation as determined by the bone mineral density (BMD) within the
      defect (144.2 +/- 7.1); about four-fold higher than that of the empty defect
      (34.9 +/- 10.7). It also showed the highest histological analysis scores with a
      high amount of bone formation within the defect, within the scaffold pores and
      along the outer surfaces of the scaffold. The basic scaffold carrying the BMP
      2/BMP-7 delivery system showed significantly higher bone formation than the
      growth factor-free basic scaffold at 6 weeks (BMD 206.8 +/- 15.7). Histological
      analysis also revealed new bone formation in close to or in direct contact with
      the construct interface. This study indicates the importance of open and
      interconnecting pore geometry on the better healing of bone defects, and that
      this effect could be further increased by supplying growth factors, as is the
      case in nature.

PMID- 22396310
TI  - Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype
      correlation in autosomal dominant centronuclear myopathy.
AB  - Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated
      with general skeletal muscle weakness, type I fiber predominance and atrophy, and
      abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the
      large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton
      and membrane trafficking in cells. To date, 40 families with CNM-related DNM2
      mutations have been described, and here we report 60 additional families
      encompassing a broad genotypic and phenotypic spectrum. In total, 18 different
      mutations are reported in 100 families and our cohort harbors nine known and four
      new mutations, including the first splice-site mutation. Genotype-phenotype
      correlation hypotheses are drawn from the published and new data, and allow an
      efficient screening strategy for molecular diagnosis. In addition to CNM,
      dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT)
      peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of
      the mutations. In this study, we discuss the possible clinical overlap of CNM and
      CMT, and the biological significance of the respective mutations based on the
      known functions of dynamin 2 and its protein structure. Defects in membrane
      trafficking due to DNM2 mutations potentially represent a common pathological
      mechanism in CNM and CMT.

PMID- 22396312
TI  - Human prostate cancer initiating cells isolated directly from localized cancer do
      not form prostaspheres in primary culture.
AB  - BACKGROUND: Recent experimental studies suggest that hierarchical expansion from
      a minor population of cancer cells with an unlimited self-renewal capacity,
      termed cancer initiating cells (CICs), drives both lethality and heterogeneity of
      prostate cancer. Human prostate CICs have been established from only two primary
      prostate cancer patients, with the remaining established CIC lines being derived
      from metastatic sites from <10 patients. This suggests that the established CIC
      lines are significant "outliers" and may not be representative of the prostate
      CICs seen clinically. Thus, there is an urgent need to develop new approaches to
      achieve the "routine" establishment of CIC containing lines, particularly derived
      from primary prostate cancers. METHODS: In the present studies, we confirmed that
      in serum free, high Ca(2+) (i.e., DMEN: F12) growth factor defined (GFD) media
      plus androgen, a large (n = 10) series of established human prostate cancer cell
      lines derived from both localized and metastatic sites characteristically self
      associate in suspension and grow as unattached spheroids, termed prostaspheres
      which contain CICs based upon their self-renewal in vitro and tumorigenicity in
      vivo. RESULTS: Unfortunately, however, while dissociated single cells from human
      primary prostate cancer tissues are viable, contain CICs as documented by their
      ability to take and proliferate as xenografts, and produce prostaspheres when
      plated with serum free, high Ca(2+) /GFD-media plus androgen onto standard tissue
      culture flask, these prostasphere do not contain CICs. CONCLUSION: The
      development of reproducibly methods to culture CICs isolated directly from
      localized cancers is still an urgent unmeet need of the prostate cancer research
      community.

PMID- 22396313
TI  - Whole blood gene expression testing for coronary artery disease in nondiabetic
      patients: major adverse cardiovascular events and interventions in the PREDICT
      trial.
AB  - The majority of first-time angiography patients are without obstructive coronary
      artery disease (CAD). A blood gene expression score (GES) for obstructive CAD
      likelihood was validated in the PREDICT study, but its relation to major adverse
      cardiovascular events (MACE) and revascularization was not assessed. Patients (N
      = 1,160) were followed up for MACE and revascularization 1 year post-index
      angiography and GES, with 1,116 completing follow-up. The 30-day event rate was
      23% and a further 2.2% at 12 months. The GES was associated with
      MACE/revascularizations (p < 0.001) and added to clinical risk scores. Patients
      with GES >15 trended towards increased >30 days MACE/revascularization likelihood
      (odds ratio = 2.59, 95% confidence interval = 0.89-9.14, p = 0.082). MACE
      incidence overall was 1.5% (17 of 1,116) and 3 of 17 patients had GES <= 15. For
      the total low GES group (N = 396), negative predictive value was 90% for
      MACE/revascularization and >99% for MACE alone, identifying a group of patients
      without obstructive CAD and highly unlikely to suffer MACE within 12 months.

PMID- 22396314
TI  - Evaluation of neonicotinoid, organophosphate and avermectin trunk injections for
      the management of avocado thrips in California avocado groves.
AB  - BACKGROUND: Trunk injections of systemic insecticides were evaluated for the
      management of avocado thrips. Insecticide residues were quantified in leaves to
      determine when after treatment, and for how long, toxic concentrations of the
      insecticides were present. Residues in fruit were quantified to determine whether
      trunk injection of insecticides might present a greater risk than traditional
      application methods for contaminating fruit. RESULTS: Residues of imidacloprid
      and dinotefuran were at least tenfold higher in leaves when trees were treated
      via trunk injection compared with soil application. Dinotefuran uptake was more
      rapid than imidacloprid, and no residues were detected within fruit. Acephate was
      also mobilized very rapidly and gave good control of thrips in bioassays;
      however, residues of acephate and its insecticidal metabolite methamidophos were
      detected in the fruit for up to 4 weeks after injection. Avermectin uptake was
      very slow, and it was ineffective against avocado thrips. CONCLUSIONS: Trunk
      injections of acephate and dinotefuran permitted rapid uptake into avocados, and
      they are strong candidates as control methods for avocado thrips. However,
      residues of organophosphates in fruit could necessitate increased preharvest
      intervals. Residues of neonicotinoids were below detection limits in fruit,
      suggesting that neonicotinoids may be the more suitable control option of the two
      chemical classes.

PMID- 22396315
TI  - Usefulness of Dynamic Urethral Resistance Relation (DURR) measurement for
      differential diagnosis between static and dynamic urinary obstruction in male
      spinal cord injury patients.
AB  - OBJECTIVE: To study the validity of Dynamic Urethral Resistance Relation (DURR)
      for differential diagnosis between static and dynamic urinay obstruction in male
      spinal cord injury patients. METHODS: A case-control study was conducted. The
      case group consisted of 24 male patients with spinal cord injury, aged under 40
      years, with detrusor-periurethral sphincter dyssynergia and bladder outlet
      obstruction (BOO) according to the urethral resistance factor (URA). The control
      group consisted of 24 male patients with no neurological lesions, aged over 49
      years, diagnosis of benign prostatic hyperplasia (BPH) and BOO according to
      Schafer's minimum urethral opening pressure (Pmuo) and the URA. A pressure/flow
      study was performed in both groups, and the DURR was recorded graphically.
      RESULTS: Both groups showed significantly different DURR characteristics with
      respect to the number of spikes (higher in the case group), the intensity of the
      first three spikes and the maximum duration of the spikes (significantly longer
      in the case group). The patients in the case group had a DURR characterized by at
      least three spikes, located throughout the whole voiding cycle (pattern A). The
      patients in the control group had a DURR mainly characterized by a spike located
      at the start of micturition and a maximum second spike located at the end of
      micturition (pattern B). CONCLUSIONS: Pattern A showed a sensitivity with respect
      to the dynamic obstruction of 79% and a specificity of 100%. The sensitivity of
      pattern B with respect to the diagnosis of static obstruction was 71% and the
      specificity was 100%.

PMID- 22396316
TI  - Clone-derived human AF-amniotic fluid stem cells are capable of skeletal myogenic
      differentiation in vitro and in vivo.
AB  - Stem cell-based therapy may be the most promising method to cure skeletal muscle
      degenerative diseases such as Duchenne muscular dystrophy (DMD) and trauma in the
      future. Human amniotic fluid is enriched with early-stage stem cells from
      developing fetuses and these cells have cardiomyogenic potential both in vitro
      and in vivo. In the present study, we investigated the characteristics of human
      amniotic fluid-derived AF-type stem (HAF-AFS) cells by flow cytometry,
      immunofluorescence staining, reverse-transcription polymerase chain reaction, and
      osteogenic and adipogenic differentiation analysis. After confirming the stemness
      of HAF-AFS cells, we tested whether HAF-AFS cells could differentiate into
      skeletal myogenic cells in vitro and incorporate into regenerating skeletal
      muscle in vivo. By temporary exposure to the DNA demethylation agent 5-aza-2'
      deoxycytidine (5-Aza dC) or co-cultured with C2C12 myoblasts, HAF-AFS cells
      differentiated into skeletal myogenic cells, expressing skeletal myogenic cell
      specific markers such as Desmin, Troponin I (Tn I) and alpha-Actinin. Four weeks
      after transplantation into cardiotoxin-injured and X-ray-irradiated tibialis
      anterior (TA) muscles of NOD/SCID mice, HAF-AFS cells survived, differentiated
      into myogenic precursor cells and fused with host myofibres. The findings that
      HAF-AFS cells differentiate into myogenic cells in vitro and incorporate in
      skeletal muscle regeneration in vivo hold the promise of HAF-AFS cell-based
      therapy for skeletal muscle degenerative diseases.

PMID- 22396317
TI  - Perceived environmental physical activity correlates among Asian Pacific Islander
      Americans.
AB  - BACKGROUND: Little is known about correlates of physical activity of Asian and
      Asian-Pacific Islander Americans (AAPI). Knowledge of these correlates could be
      useful in promoting physical activity. PURPOSE: to identify demographic and
      environmental correlates of physical activity among AAPI. METHODS: Participants
      resided in the Las Vegas, Nevada area, and completed a 52-item telephone
      administered questionnaire that assessed physical activity behavior,
      environmental supports for physical activity and demographic factors.
      Environmental factors included the presence of neighborhood sidewalks, park
      availability, and nearby grocery stores were combined to create the variable
      "environmental physical activity supports" (EPAS). Neighborhood crime,
      pleasantness of the neighborhood for walking, and the presence of loose dogs
      combined to form "neighborhood safety." Logistic regression was used to identify
      predictors of physical activity. Potential predictors included age, gender, BMI,
      employment, educational attainment, neighborhood safety, and EPAS. RESULTS: 263
      respondents completed the survey. With the exception of living near a grocery
      store, respondents reported residing in neighborhoods that are generally
      supportive of physical activity. However, EPAS was the sole significant predictor
      of physical activity behavior (OR = 1.52, CI = 1.06-2.17). Age and educational
      attainment unexpectedly failed to predict physical activity. CONCLUSIONS:
      Supportive physical activity environments associate with physical activity
      behavior among AAPI.

PMID- 22396318
TI  - Engineering of micro- and nanostructured surfaces with anisotropic geometries and
      properties.
AB  - Widespread approaches to fabricate surfaces with robust micro- and nanostructured
      topographies have been stimulated by opportunities to enhance interface
      performance by combining physical and chemical effects. In particular, arrays of
      asymmetric surface features, such as arrays of grooves, inclined pillars, and
      helical protrusions, have been shown to impart unique anisotropy in properties
      including wetting, adhesion, thermal and/or electrical conductivity, optical
      activity, and capability to direct cell growth. These properties are of wide
      interest for applications including energy conversion, microelectronics, chemical
      and biological sensing, and bioengineering. However, fabrication of asymmetric
      surface features often pushes the limits of traditional etching and deposition
      techniques, making it challenging to produce the desired surfaces in a scalable
      and cost-effective manner. We review and classify approaches to fabricate arrays
      of asymmetric 2D and 3D surface features, in polymers, metals, and ceramics.
      Analytical and empirical relationships among geometries, materials, and surface
      properties are discussed, especially in the context of the applications mentioned
      above. Further, opportunities for new fabrication methods that combine
      lithography with principles of self-assembly are identified, aiming to establish
      design principles for fabrication of arbitrary 3D surface textures over large
      areas.

PMID- 22396320
TI  - Arrays in postnatal and prenatal diagnosis: An exploration of the ethics of
      consent.
AB  - The introduction of genome-wide arrays in postnatal and prenatal diagnosis raises
      challenging ethical issues. Here, we explore questions with regard to the ethics
      of consent. One important issue is whether informed consent for genome-wide array
      based testing is in fact feasible, given the wide range of possible outcomes and
      related options. The proposed alternative of "generic consent" will have to be
      studied in practice. From an ethical point of view, the question is whether
      consent would still be sufficiently "informed" in a generic approach. Another
      issue that has not yet been given much attention is how far parents, or pregnant
      women and their partners, should be allowed to determine the range of possible
      outcomes that will or will not be reported back to them. The scope and limits of
      parents' and prospective parents' right to know or not to know are far from
      clear. The complex normative issues on the content and weight of these rights can
      only be answered by taking full account of the rights and interests of all the
      parties involved: prospective and actual parents, children, and relatives. This
      paper is the result of a working group meeting preceding the European Society of
      Human Genetics 2011 Conference, where these issues were addressed.

PMID- 22396319
TI  - Adaptive auto-regulation of androgen receptor provides a paradigm shifting
      rationale for bipolar androgen therapy (BAT) for castrate resistant human
      prostate cancer.
AB  - Cell culture/xenograft and gene arrays of clinical material document that
      development of castration resistant prostate cancer (CRPC) cells involves
      acquisition of adaptive auto-regulation resulting in >25-fold increase in
      Androgen Receptor (AR) protein expression in a low androgen environment. Such
      adaptive AR increase paradoxically is a liability in castrated hosts, however,
      when supraphysiologic androgen is acutely replaced. Cell synchronization/anti
      androgen response is due to AR binding to replication complexes (RC) at origin of
      replication sites (ORS) in early G1 associated with licensing/restricting DNA for
      single round of duplication during S-phase. When CRPC cells are acutely exposed
      to supraphysiologic androgen, adaptively increased nuclear AR is over-stabilized,
      preventing sufficient degradation in mitosis, inhibiting DNA re-licensing, and
      thus death in the subsequent cell cycle. These mechanistic results and the fact
      that AR/RC binding occurs in metastatic CRPCs directly from patients provides a
      paradigm shifting rationale for bipolar androgen therapy (BAT) in patient
      progressing on chronic androgen ablation. BAT involves giving sequential cycles
      alternating between periods of acute supraphysiologic androgen followed by acute
      ablation to take advantage of vulnerability produced by adaptive auto-regulation
      and binding of AR to RC in CRPC cells. BAT therapy is effective in xenografts and
      based upon positive results has entered clinical testing.

PMID- 22396321
TI  - Pathological assessment of microinvasive carcinoma of the breast.
AB  - BACKGROUND: Microinvasive breast cancer (T1mi) is considered as a precursor of
      invasive cancer developing from ductal carcinoma in situ (DCIS). This study
      discussed the clinicopathological and immunohistochemical features of T1mi by
      comparing those of ductal carcinoma in situ (Tis) and T1a to assess the nature
      and causes of the progression of Tis into invasive cancer. METHODS: Three hundred
      and ninety-two Tis, 32 T1mi, and 141 T1a lesions which were pathologically
      diagnosed in surgical specimens between 2006 and 2009 were analyzed
      retrospectively. T1mi was defined as a tumor no greater than 1 mm in its greatest
      dimensions, and T1a was defined as a tumor larger than 1 mm but no greater than 5
      mm. RESULTS: The frequency of the comedo type was significantly higher in T1mi
      (68.8%) than in Tis (13.8%) (p < 0.001) and T1a (30.5%) (p < 0.001). Estrogen
      receptor (ER) negative-HER2 positive type was more frequent in T1mi (46.9%) than
      in Tis (8.7%) (p < 0.001) and T1a (10.6%) (p < 0.001). There was a significant
      difference in Ki-67 index between T1mi (35.2 +/- 19.2%) and Tis (18.8 +/- 14.5%)
      (p < 0.001). T1mi had higher rates of comedo type and ER negative-HER2 positive
      type. CONCLUSION: Comedo type and ER negative-HER2 positive type were found more
      frequently in T1mi than in Tis and T1a. There could be different biological
      mechanisms for promoting Tis into invasive cancer from enlarging invasive cancer.

PMID- 22396322
TI  - Malignant lymphoma of the breast in a male patient: ultrasound imaging features.
AB  - Non-Hodgkin lymphoma (NHL) of the breast is a rare disease. Herein, we report a
      rare case of secondary involvement of the breast by NHL in a male patient and the
      ultrasound imaging findings. A 70-year-old man noticed an induration of the
      subareolar region of the right breast. He had been diagnosed as having mantle
      cell lymphoma 5 years before and treated with several series of
      chemoradiotherapy. On supine examination, palpation revealed bilateral breast
      enlargement, but detection of a lump was difficult. Ultrasonography showed a
      hypoechoic non-mass image-forming lesion in the subareolar region of the right
      breast. The final pathological diagnosis was recurrence of mantle cell lymphoma
      in the right breast. The diagnosis of malignant lymphoma of the breast by imaging
      modalities is difficult because there are no specific features. Breast lymphoma
      should be included with gynecomastia and breast cancer in the differential
      diagnosis of male patients with breast enlargement.

PMID- 22396324
TI  - Tracking of physical activity with accelerometers over a 2-year time period.
AB  - BACKGROUND: Limited data exist of tracking and changes in accelerometer-measured
      physical activity in children. METHODS: Physical activity was assessed by
      accelerometers for 4 days in 167 children (boys, n = 90; girls n = 77) age 9.8 +/
      0.6 years. Follow-up measurement was made 2.0 +/- 0.1 yrs later (range 1.9-2.1
      yrs). General physical activity (GPA) was defined as mean count/minute. Minutes
      of inactivity; light, moderate, and vigorous physical activity (LMVPA); moderate
      and vigorous physical activity (MVPA); and vigorous physical activity (VPA) per
      day were calculated both as absolute values and as percentage of total
      registration time. RESULTS: Spearman rank order correlation indicated low
      tracking of MVPA and VPA in girls (r = .25-0.33, P < .05), and low-moderate
      tracking of GPA, inactivity, LMVPA, MVPA and VPA in boys (r = .23-0.40, P < .05).
      Time in inactivity increased at follow-up by 5%-14%. Most of the assessed
      physical activity variables were decreased at follow-up by 6% to 30%.
      CONCLUSIONS: Physical activity tracks at a low-moderate degree from age 10-12
      years, which confirm previous investigations that have used self-report
      assessments. The low-moderate tracking of physical activity variables indicate
      that those who were most active initially remained most active. Increasing
      inactive behavior was observed and that several other physical activity variables
      were decreased at follow-up.

PMID- 22396323
TI  - The association of in-hospital major bleeding with short-, intermediate-, and
      long-term mortality among older patients with non-ST-segment elevation myocardial
      infarction.
AB  - AIMS: Bleeding complications have been associated with short-term mortality in
      patients with non-ST-segment elevation myocardial infarction (NSTEMI). Their
      association with long-term outcomes is less clear. This study examines mortality
      associated with in-hospital bleeding during NSTEMI over time intervals starting
      from hospital discharge and extending past 3 years. METHODS AND RESULTS: We
      studied 32 895 NSTEMI patients aged >=65 years, using patient-level data from the
      CRUSADE registry linked with Medicare claims data. We assessed the association of
      in-hospital major bleeding with short (30 days), intermediate (1 year), and long
      term (3 years) mortality among hospital survivors overall, as well as in those
      patients treated with or without a percutaneous coronary intervention (PCI). We
      calculated adjusted hazard ratios (HRs) for mortality for bleeders vs. non
      bleeders over time intervals from: (i) discharge to 30 days; (ii) 31 days to 1
      year; (iii) 1 year to 3 years; and (iv) beyond 3 years. Overall, 11.9% (n = 3902)
      had an in-hospital major bleeding event. Cumulative mortality was higher in those
      who had a major bleed vs. those without at 30 days, 1 year, and 3 years. Even
      after adjustment, major bleeding continued to be significantly associated with
      higher mortality over time in the overall population: (i) discharge to 30 days
      [adjusted HR 1.33; 95% confidence interval (CI) 1.18-1.51]; (ii) 31 days to 1
      year (1.19; 95% CI 1.10-1.29); (iii) 1 year to 3 years (1.09; 95% CI 1.01-1.18),
      and (iv) attenuating beyond 3 years (1.14; 95% CI 0.99-1.31). In-hospital
      bleeding among patients treated with PCI continued to be significantly associated
      with higher adjusted mortality even beyond 3 years (1.25; 95% CI 1.01-1.54).
      CONCLUSION: In-hospital major bleeding is associated with short-, intermediate-,
      and long-term mortality among older patients hospitalized for NSTEMI-this
      association is strongest within the first 30 days, but remains significant long
      term, particularly among PCI-treated patients. Despite a probable early hazard
      related to bleeding, the longer duration of risk in patients who bleed casts
      doubt on its causal relationship with long-term mortality. Rather, major bleeding
      likely identifies patients with an underlying risk for mortality.

PMID- 22396325
TI  - Piezo-phototronic effect-induced dual-mode light and ultrasound emissions from
      ZnS:Mn/PMN-PT thin-film structures.
AB  - Electric-field-controllable luminescence of a ZnS:Mn/PMN-PT system is
      demonstrated. The light-emission of ZnS:Mn is caused by the piezoelectric
      potential, resulting from the converse piezoelectric effect of the PMN-PT
      substrate. Simultaneous generation of light and ultrasound waves is observed in
      this single system, which offers great potential to develop a dual-modal source
      combing light and ultrasonic waves for various applications.

PMID- 22396326
TI  - Re: usefulness of dynamic urethral resistance relation (DURR) measurement for
      differential diagnosis between static and dynamic urinary obstruction in male
      spinal cord injury patients. Neurourol urodyn 2012;31:549-55.

PMID- 22396327
TI  - Large-scale objective association of mouse phenotypes with human symptoms through
      structural variation identified in patients with developmental disorders.
AB  - Copy number variants (CNVs) are thought to underlie many human developmental
      abnormalities. However, it is unclear how many of these CNVs exert their
      pathogenic effects or, in particular, how distinct CNVs at dispersed loci can
      give rise to the same abnormality. We hypothesize that the mouse orthologs of
      genes whose copy number change gives rise to the same human abnormality might
      also yield a similar phenotype when disrupted in mice. Thus, by bringing together
      a large number of disparate CNVs, we may be able to identify an unusually
      overrepresented phenotype among the affected genes' mouse orthologs. We obtained
      1,624 de novo CNVs identified in patients with developmental abnormalities from
      Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources
      and European Cytogeneticists Association Register of Unbalanced Chromosome
      Aberrations database. Forming CNV sets for each of 1,088 distinct human
      abnormalities, we were able to associate a total of 143 (13%) human abnormalities
      with mouse model phenotypes. Although many mouse phenotypes are readily
      comparable to their associated human abnormality, others are less so, generating
      novel biological hypotheses. Of the 2,086 candidate genes that contribute to
      these associations, 65% have not been previously associated with human disease in
      Online Mendelian Inheritance in Man, and their distribution suggests both
      extensive pleiotropy and epistasis while also proposing a small number of simple
      additive consequences.

PMID- 22396328
TI  - Curcumin protects against regional myocardial ischemia/reperfusion injury through
      activation of RISK/GSK-3beta and inhibition of p38 MAPK and JNK.
AB  - BACKGROUND: Curcumin, the active ingredient of turmeric (Curcuma longa), is known
      to have anti-inflammatory and antioxidative properties. The present study was
      aimed to determine the effect of curcumin in regional myocardial
      ischemia/reperfusion (I/R) injury and its underlying mechanisms involving the
      role of prosurvival kinases and apoptotic kinases. METHODS: Sprague-Dawley rats
      (n = 109) subjected to a 30-minute left anterior descending coronary artery (LAD)
      occlusion followed by reperfusion were assigned to receive saline (control),
      curcumin (100 mg/kg), wortmannin (inhibitor of phosphatidylinositol-3-OH kinase
      [PI3K]-Akt), wortmannin + curcumin, U0126 (inhibitor of extracellular signal
      regulated kinase [ERK1/2]), U0126 + curcumin, SB216763 (inhibitor of glycogen
      synthase kinase [GSK-3beta]), and SB216763 + curcumin 20 minutes before LAD
      occlusion. Infarct size was measured after 2 hours of reperfusion by triphenyl
      tetrazolium chloride staining. The phosphorylation of Akt, ERK1/2, GSK-3beta,
      p38, and c-Jun N-terminal kinases (JNK) was determined by immunoblotting after 10
      minutes of reperfusion. RESULTS: Curcumin significantly reduced the infarct size
      compared with the control (33.1% +/- 6.2% vs 50.1% +/- 3.9%; P < .05). Wortmannin
      or U0126 alone did not affect the infarct size but abolished the curcumin-induced
      cardioprotective effect. Curcumin significantly enhanced the phosphorylation of
      Akt, ERK1/2, and GSK-3beta, while it reduced that of p38 and JNK. Wortmannin or
      U0126 abolished enhanced phosphorylation of GSK-3beta induced by curcumin.
      SB216763 alone or combined with curcumin reduced the infarct size and enhanced
      phosphorylation of GSK-3beta compared with the control. CONCLUSIONS:
      Preconditioning by curcumin effectively protects against regional myocardial I/R
      injury through the activation of prosurvival kinases involving PI3K-Akt, ERK1/2,
      and GSK-3beta, and attenuation of p38 and JNK.

PMID- 22396329
TI  - Diversity and complexity of roles of granule cells in the cerebellar cortex.
      Editorial.
AB  - The cerebellar granule cell, the most numerous neurons in the brain, forms the
      main excitatory neuron of the cerebellar cortical circuitry. Granule cells are
      synaptically connected with both mossy fibers and Golgi cells inside specialized
      structures called glomeruli, and thereby, they are subject to both feed-forward
      and feed-back inhibition. Their unique architecture with about four dendrites and
      a single axon ascending in the cerebellar cortex to bifurcate into two parallel
      fibers making synapses with Purkinje neurons has attracted numerous scientists.
      Recent advances show that they are much more than just relays of mossy fibers.
      They perform diverse and complex transformations in the spatiotemporal domain.
      This special issue highlights novel avenues in our understanding of the roles of
      this key neuronal population of the cerebellar cortex, ranging from developmental
      up to physiological and pathological points of view.

PMID- 22396330
TI  - A note on the definition and the development of cerebellar Purkinje cell zones.
AB  - The definition of Purkinje cell zones by their white matter compartments, their
      physiological properties, and their molecular identity and the birthdate of their
      Purkinje cells will be reviewed.

PMID- 22396331
TI  - The functional role of the cerebellum in visually guided tracking movement.
AB  - We propose a new method to provide a functional interpretation of motor commands
      (i.e., muscle activities) and their relationship to movement kinematics. We
      evaluated our method by analyzing the motor commands of normal controls and
      patients with cerebellar disorders for visually guided tracking movement of the
      wrist joint. Six control subjects and six patients with cerebellar disorders
      participated in this study. We asked the subjects to perform visually guided
      smooth tracking movement of the wrist joint with a manipulandum, and recorded the
      movements of the wrist joint and activities of the four wrist prime movers with
      surface electrodes. We found a symmetric relationship between the second-order
      linear equation of motion for the wrist joint and the linear sum of activities of
      the four wrist prime movers. The symmetric relationship determined a set of
      parameters to characterize the muscle activities and their similarity to the
      components of movement kinematics of the wrist joint. We found that muscle
      activities of the normal controls encoded both the velocity and the position of
      the moving target, resulting in precise tracking of the target. In contrast,
      muscle activities of the cerebellar patients were characterized by a severer
      impairment for velocity control and more dependence on position control,
      resulting in poor tracking of the smoothly moving target with many step-like
      awkward movements. Our results suggest that the cerebellum plays an important
      role in the generation of motor commands for smooth velocity and position
      control.

PMID- 22396332
TI  - Physiological performance and mating system in Clarkia (Onagraceae): does
      phenotypic selection predict divergence between sister species?
AB  - PREMISE OF THE STUDY: The evolution of self-fertilization often occurs in
      association with other floral, life history, and fitness-related traits. A
      previous study found that field populations of Clarkia exilis (a predominantly
      autogamous selfer) and its sister species, Clarkia unguiculata (a facultative
      outcrosser) differ in mean photosynthetic rates and instantaneous water use
      efficiency (WUE(i)). Here, we investigate the strength and direction of selection
      on these traits in multiple populations of each taxon to determine whether
      natural selection may contribute to the phenotypic differences between them.
      METHODS: In spring 2008, we measured instantaneous gas exchange rates in nine
      populations during vegetative growth (Early) and/or during flowering (Late). We
      conducted selection gradient analyses and estimated selection differentials
      within populations and across pooled conspecific populations to evaluate the
      strength, direction, and consistency of selection on each trait early and late in
      the season. KEY RESULTS: The direction and relative strength of selection on
      photosynthetic rates in these taxa corresponds to the phenotypic difference
      between them; C. exilis has higher photosynthetic rates than C. unguiculata, as
      well as stronger, more consistent selection favoring rapid photosynthesis
      throughout the growing season. Patterns of selection on transpiration, WUE(i),
      and the timing of flowering progression are less consistent with phenotypic
      differences (or lack thereof) between taxa. CONCLUSIONS: We detected several
      examples where selection was consistent with the phenotypic divergence between
      sister taxa, but there were also numerous instances that were equivocal or in
      which selection did not predict the realized phenotypic difference between taxa.

PMID- 22396333
TI  - Origins and close relatives of a semi-domesticated neotropical fruit tree:
      Chrysophyllum cainito (Sapotaceae).
AB  - PREMISE OF THE STUDY: Understanding patterns and processes associated with
      domestication has implications for crop development and agricultural biodiversity
      conservation. Semi-domesticated crops provide excellent opportunities to examine
      the interplay of natural and anthropogenic influences on plant evolution. The
      domestication process has not been thoroughly examined in many tropical perennial
      crop species. Chrysophyllum cainito (Sapotaceae), the star apple or caimito, is a
      semi-domesticated species widely cultivated for its edible fruits. It is known to
      be native to the neotropics, but the precise geographic origins of wild and
      cultivated forms are unresolved. METHODS: We used nuclear ribosomal ITS sequences
      to infer phylogenetic relationships among C. cainito and close relatives (section
      Chrysophyllum). We employed phylogeographic approaches using ITS and plastid
      sequence data to determine geographic origins and center(s) of domestication of
      caimito. KEY RESULTS: ITS data suggest a close relationship between C. cainito
      and C. argenteum. Plastid haplotype networks reveal several haplotypes unique to
      individual taxa but fail to resolve distinct lineages for either C. cainito or C.
      argenteum. Caimito populations from northern Mesoamerica and the Antilles exhibit
      a subset of the genetic diversity found in southern Mesoamerica. In Panama,
      cultivated caimito retains high levels of the diversity seen in wild populations.
      CONCLUSIONS: Chrysophyllum cainito is most closely related to a clade containing
      Central and South American C. argenteum, including subsp. panamense. We
      hypothesize that caimito is native to southern Mesoamerica and was domesticated
      from multiple wild populations in Panama. Subsequent migration into northern
      Mesoamerica and the Antilles was mediated by human cultivation.

PMID- 22396334
TI  - Readiness signs used to define the proper moment to start toilet training: a
      review of the literature.
AB  - Confusion exists about when to start toilet training, which causes stress and
      anxiety. Another consequence can be the actual postponement of the toilet
      training process, which has created extra social problems. Therefore, in this
      review we will focus on the proper moment to start toilet training, more specific
      on readiness signs. This will clarify on which topics further research is
      necessary. We searched databases for publications on toilet training. Next, we
      gathered information about the normal development of healthy children and at
      which age skills needed for each readiness sign are acquired. Twenty-one
      readiness signs were found. Our results show that there is no consensus on which
      or how many readiness signs to use. Depending on the readiness sign, the moment
      to start toilet training can vary a lot. More studies are needed to define which
      readiness signs are most important and how to detect them easily.

PMID- 22396335
TI  - Organic-inorganic hybrid functional carbon dot gel glasses.
AB  - Silane pre-functionalized carbon dots, arbitrarily doped (0-100% scale) carbon
      dot nanohybrid gel glasses and macrostructures with high luminescence (quantum
      yields = 47% and 88%, respectively) and broadband optical limiting properties
      (532 and 1064 nm) are reported. These glasses are optically, thermally, and
      mechanically stable, as well as highly transmissive (ca. 90%) in the 400-1350 nm
      region.

PMID- 22396336
TI  - Mental illness, criminality, and citizenship revisited.

PMID- 22396337
TI  - Reflections and narratives: new to The Journal and to professional ethics.

PMID- 22396338
TI  - But he knew it was wrong: evaluating adolescent culpability.
AB  - Forensic psychiatric evaluators of adolescent defendants are often asked to
      address open-ended questions that affect what court an adolescent will be tried
      in and what sentence he might receive. Such questions often involve the extent to
      which the adolescent should be considered less culpable than an adult who has
      committed a similar offense. Assessing partial or diminished culpability in an
      adolescent is difficult because the concept of partial culpability is complex,
      assessment methods are inexact, and the implications for legal disposition are
      often not clear. This article suggests 10 factors a forensic evaluator may wish
      to consider in reaching opinions about an adolescent's culpability: appreciation
      of wrongfulness, ability to conform to law, developmental course of aggression
      and impulsivity, psychosocial immaturity (including time sense, susceptibility to
      peer pressure, risk-taking, and ability to empathize), environmental
      circumstances, peer group norms, out-of-character action, incomplete personality
      development, mental illness, and reactive attitudes toward the offense.

PMID- 22396339
TI  - Commentary: Building a developmental-ecological model of criminal culpability
      during adolescence.
AB  - In this issue of The Journal, Dr. Peter Ash offers the American Academy of
      Psychiatry and the Law some ideas on developmentally informed assessment of
      criminal culpability during adolescence. After highlighting issues that
      complicate the definition and assessment of criminal culpability, Ash lists 10
      constructs that he believes should be carefully considered by forensic clinicians
      in developing opinions about legal responsibility for a crime committed by a
      minor. I applaud Ash for beginning a dialogue on the clinical dimension of this
      topic, and I appreciate his emphasis on the need for developmentally informed
      assessment of juvenile defendants. In this commentary, I briefly illustrate how
      the principles of developmental psychopathology can be used to articulate a
      developmental-ecological model of criminal culpability for use by forensic
      clinicians in the assessment of younger defendants, as the courts more broadly
      accept the concept of mitigation of legal responsibility by reason of
      developmental immaturity.

PMID- 22396340
TI  - Defendant remorse, need for affect, and juror sentencing decisions.
AB  - Defendant remorse is generally accepted as a mitigating factor in capital murder
      sentencing in the legal system. The current study addressed whether verbal and
      nonverbal expressions of defendant remorse are perceived as remorseful by mock
      jurors. Moreover, this study investigated the associations of defendant behaviors
      and mock juror need for affect on sentencing decisions. Participants watched a
      video of a defendant depicting either high or low levels of verbal and nonverbal
      remorseful behavior. Results indicated that nonverbal behaviors were more
      important than verbal cues for perception of remorse. Incongruent verbal and
      nonverbal behavior, as well as mock juror willingness to approach emotional
      situations (i.e., high need for affect (NFA)) resulted in more lenient sentences
      for defendants. Implications for the remorse construct, for witness preparation,
      and for jury selection are discussed.

PMID- 22396341
TI  - Commentary: Pursuing justice in death penalty trials.
AB  - The capital trial, by its nature, is fraught with emotionally disturbing elements
      that jurors must face when deciding the ultimate fate of a guilty defendant. A
      confluence of mitigating and aggravating factors influences a capital jury's
      decision to impose a sentence of death. The presence or absence of defendant
      remorse in these cases may make all the difference in whether a capital
      defendant's life is spared. This commentary examines the onerous emotional toll
      encountered by capital jurors in light of the findings of Corwin and colleagues
      regarding defendant remorse and juror's need for affect. The commentary also
      presents practical and ethics-related considerations that should be kept in mind
      when reflecting on their study.

PMID- 22396342
TI  - Commentary: Perception of remorse by mock jurors in a capital murder trial.
AB  - The study by Corwin et al. adds to the emerging but limited data on the impact of
      defendant remorse on sentencing decisions. The authors studied verbal and
      nonverbal expressions of defendant remorse and whether they were perceived as
      remorseful by mock jurors. They found that incongruent verbal and nonverbal
      behavior, as well as mock jurors' willingness to approach emotional situations,
      resulted in more lenient sentences for defendants. An overarching and as yet
      unanswered validity concern regarding this line of research in general is whether
      the use of undergraduate mock jurors reliably models real jurors in actual
      courtroom settings.

PMID- 22396343
TI  - Physician boundary violations in a physician's health program: a 19-year review.
AB  - Managing and treating physicians with professional boundary violations is of
      paramount importance with vast implications for public safety. Physician Health
      Programs (PHPs) evaluate and monitor many, if not most, physicians receiving care
      for these abuses. We conducted a chart review of 120 physicians monitored for
      boundary violations. We made intergroup and intragroup comparisons (i.e.,
      examining nonpatient, patient nonsexual, and patient sexual offenses). The
      violator group as a whole differed from the general PHP population, in that more
      were men between 40 and 49 years of age. More of the violators were mandated for
      evaluation and reported an abusive history. The rate of psychiatrists exceeded
      that typically seen by the PHP. Other differences were found according to the
      type of violation committed. Post hoc analysis revealed that physician-patients
      with a history of prior boundary violations were more likely to commit violations
      of a sexual nature. No further incidents were reported for 88 percent of the
      cohort.

PMID- 22396345
TI  - From schadenfreude to contemplation: lessons for forensic experts.
AB  - In 2005, the Chief Coroner of Ontario instituted a review into 45 cases of
      criminally suspicious child deaths about which a prominent pediatric forensic
      pathologist had expressed an opinion that the cause was homicide. Subsequently, a
      provincial inquiry was called to review the practice and oversight of pediatric
      forensic pathology in Ontario and to make recommendations to restore and enhance
      public confidence in forensic pathology. Recommendations from the inquiry
      addressed medical subspecialization, the evidentiary basis for expert opinion,
      oversight of the profession, and development of best forensic practices. Although
      the inquiry focused on pathologists, it is clear that these recommendations have
      significant implications for all forensic professions, including forensic
      psychiatry. This article summarizes the inquiry report and considers the
      potentially important implications for forensic psychiatry.

PMID- 22396344
TI  - Classics in psychiatry and the law: Francis Wharton on involuntary confessions.
AB  - Philadelphia attorney Francis Wharton was a key intellectual figure in linking
      the sciences of medicine and law. In 1860, he published a monograph on
      involuntary confessions, which represented the closing chapter of Wharton and
      Stille's Treatise on Medical Jurisprudence. He had already published A Monograph
      on Mental Unsoundness in 1855, the first book of the Treatise in its first
      edition. Wharton was convinced that many criminals had an inner compulsion to
      confess or to be caught, explained as divine jurisprudence. His remarks on
      confessions include a typology spanning psychodynamics to police tactics, using
      contemporaneous, historical, and literary examples. This remarkable document
      provides insight into the dynamics of unintended and involuntary confessions and
      is compatible, in part, with current scholarship. The author contrasts Wharton's
      schema with those of his English predecessor Jeremy Bentham, the psychoanalyst
      Theodore Reik, and others, and concludes that it represents an important
      transition toward a psychological approach to the criminology of confessions.

PMID- 22396346
TI  - Competency restoration treatment: differences between defendants declared
      competent or incompetent to stand trial.
AB  - Archival data of inpatient defendants referred for competency restoration were
      used to make comparisons between those who were restored to competency (CST; n =
      43) and those who remained incompetent (IST; n = 15). The groups did not differ
      on demographic variables, intellectual capacity, type of offense (violent versus
      nonviolent), clinical diagnoses, substance abuse, or psychotic symptomatology, as
      measured by the Brief Psychiatric Rating Scale. However, the CST group performed
      significantly better than the IST group on both the initial and final Georgia
      Court Competency Test and Global Assessment of Functioning scale. Psychotic
      symptom severity decreased significantly only in the CST group, and the CST group
      was discharged significantly sooner (7.7 +/- 8.6 months) than the IST group (17.9
      +/- 7.0 months). While consistent with prior research, this is the first study to
      compare both psycholegal comprehension and specific clinical symptoms in
      defendants before and after competency restoration treatment.

PMID- 22396347
TI  - The involuntary medication of Jared Loughner and pretrial jail detainees in
      nonmedical correctional facilities.
AB  - In United States v. Loughner the Ninth Circuit will soon address the
      constitutionality of involuntarily medicating an incompetent pretrial defendant
      through a Harper order that could serve to render him competent to stand trial
      without the added procedural protection of a judicial hearing. Judicial support
      for applying Harper orders to pretrial defendants is likely to be used to justify
      Harper orders for pretrial jail detainees, allowing them to be involuntarily
      medicated in a jail setting, even though the place of involuntary medication was
      not at issue in the Loughner case. Because of the critical clinical, ethics
      related, and legal concerns for such practice, the potential misapplication of
      the Loughner ruling should be considered by the Ninth Circuit before rendering
      its decision. This is, however, unlikely because the Ninth Circuit has just
      determined that Loughner will continue to be involuntarily medicated, regardless
      of whether this occurs in a hospital or in a nonmedical correctional facility.

PMID- 22396348
TI  - Adapting the cultural formulation for clinical assessments in forensic
      psychiatry.
AB  - Even as forensic psychiatrists have increasingly contemplated the role of culture
      in forensic psychiatry, practical cultural evaluations remain an under-theorized
      area with scant research. Older conceptions of cultural competence may risk
      stereotyping the evaluee on the basis of perceived group characteristics. This
      article offers a revision of the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, Text Revision (DSM-IV) Outline for Cultural
      Formulation for use in forensic psychiatry by adjusting its formal guidelines
      with recommendations from the forensic mental health literature. As a person
      centered method of conducting the interview, the Cultural Formulation probes
      cultural explanations of identity, illness, social support, functioning, and
      interaction with the medical and legal systems. In line with other psychiatric
      subspecialties, future research in forensic psychiatry can examine the extent to
      which the Cultural Formulation helps trainees with cultural competence,
      reconfigures diagnosis and treatment, and alters legal outcomes such as length of
      sentence.

PMID- 22396349
TI  - Intentional ingestion and insertion of foreign objects: a forensic perspective.
AB  - Intentional ingestion and insertion of foreign objects is a topic that has
      generated mounting interest among medical professionals over the past two
      decades. When featured in the literature, it has been typically discussed in
      medical subdisciplines, such as emergency medicine, surgery, gastroenterology,
      and urology. However, in-depth exploration of this multidimensional phenomenon in
      the field of psychiatry has thus far been limited. This article presents
      illustrative clinical vignettes from forensic practice of deliberate
      ingestion/insertion of objects and then examines specific aspects of this
      behavior that are critical to achieving a better understanding of it. The
      clinical, legal, and ethics-related implications surrounding this conduct are
      also explored. By taking a comprehensive approach, the aim is to foster a greater
      appreciation of this syndrome by clinicians and ultimately to arrive at improved
      practice guidelines surrounding these cases, including a more informed
      therapeutic plan and an enhanced management approach.

PMID- 22396350
TI  - The parental alienation debate belongs in the courtroom, not in DSM-5.
AB  - The DSM-5 Task Force is presently considering whether to adopt parental
      alienation disorder (PAD) as a mental illness. Although controversy has
      surrounded PAD since its inception in 1985, pro-PAD groups and individuals have
      breathed new life into the push to establish it as a mental health diagnosis. In
      this analysis, we argue that it would be a serious mistake to adopt parental
      alienation disorder as a formal mental illness in the Diagnostic and Statistical
      Manual of Mental Disorders, Fifth Edition (DSM-5).

PMID- 22396351
TI  - Becoming a real doctor: my transition from fellowship to faculty.

PMID- 22396352
TI  - Delusional disorder.

PMID- 22396353
TI  - Scholarly, clinical, and legal questions concerning hebephilia, with particular
      reference to sexually violent predator civil commitment proceedings.

PMID- 22396354
TI  - The relationship between continence and perineal body tone before and after
      radical prostatectomy: a pilot study.
AB  - INTRODUCTION: Recent preliminary studies showed that tonic-trophic
      characteristics of the pelvic muscles are related to postoperative male urinary
      incontinence. The aim of the current study was to test whether perineal body tone
      (PBT), evaluated using the Beco perineometer (Perineocaliper), is related to
      urinary continence recovery after robot-assisted laparoscopic prostatectomy
      (RALP). MATERIALS AND METHODS: The study population consisted of 48 patients who
      underwent RALP between January and July 2009. Surgical interventions were
      performed by a single surgeon and patients were evaluated by a single
      physiotherapist. All patients were taught pelvic floor muscle exercises (PFME).
      PBT was evaluated in each patient preoperatively, as well 30 days and 3 months
      after surgery. In addition, patients were evaluated with a 24-hr pad-test and the
      International Consultation on Incontinence-questionnaire (ICI-Q). RESULTS: Mean
      age at surgery was 65.5 years (range 46-63). Twenty-four patients underwent a
      bilateral nerve-sparing procedure (50%). One-month after surgery, 25 (52.1%)
      patients were continent while 23 (47.9%) patients were still incontinent. A
      statistically significant difference in preoperative perineometric measures was
      observed between continent and incontinent patients (mean 1.36 cm vs. 0.80 cm; P
      < 0.001). This difference was even more pronounced when comparing postoperative
      perineometric measures (mean 1.24 cm vs. 0.43 cm; P < 0.001). Evaluation of
      patients 3 months after surgery showed an increase in perineometric measures
      (mean increase 0.76 cm). The increase was significantly higher in patients who
      became continent after 3 months relative to patients who were still incontinent
      despite PFME (mean perineometric measures 1.45 cm vs. 1.00 cm; P = 0.021).
      CONCLUSIONS: Our results demonstrate that urinary continence recovery is related
      to PBT recovery. Further studies are needed to confirm whether perineometric
      measures may be used as a predictive tool for the risk-stratification of
      postoperative UI.

PMID- 22396355
TI  - A hybrid piezoelectric structure for wearable nanogenerators.
AB  - A hybrid-fiber nanogenerator comprising a ZnO nanowire array, PVDF polymer and
      two electrodes is presented. Depending on the bending or spreading action of the
      human arm, at an angle of ~90 degrees , the hybrid fiber reaches electrical
      outputs of ~0.1 V and ~10 nA cm(-2) . The unique structure of the hybrid fiber
      may inspire future research in wearable energy-harvesting technology.

PMID- 22396356
TI  - A time for review.

PMID- 22396357
TI  - Le moment de faire un bilan.

PMID- 22396358
TI  - Une annee de premieres a l'AUC.

PMID- 22396359
TI  - A year of firsts at the CUA.

PMID- 22396360
TI  - Importance of patient compliance in small renal mass active surveillance.

PMID- 22396362
TI  - Estrogens in the time of blood-thinners.

PMID- 22396361
TI  - Management of kidney cancer: canadian kidney cancer forum consensus update 2011.

PMID- 22396363
TI  - Intrathecal clonidine added to small-dose bupivacaine prolongs postoperative
      analgesia in patients undergoing transurethral surgery.
AB  - INTRODUCTION: The aim of this prospective, double-blinded study was to
      investigate the effects of clonidine in co-administration with bupivacaine during
      spinal anesthesia, regarding the onset and regression of motor and sensory block,
      postoperative analgesia and possible side effects. METHODS: We randomly selected
      66 male patients (age 35 to 70), from the American Society of Anesthesiologists
      (ASA) class I-II; these patients were scheduled for transurethral surgical
      procedures. These patients were randomly allocated into two groups of 33 patients
      each: group B (bupivacaine) only received 0.5% isobaric bupivacaine 7.5 mg
      intrathecally and group BC (bupivacaine + clonidine) received bupivacaine 7.5 mg
      and clonidine 25 MUg intrathecally. We performed the spinal anesthesia at a level
      of L3-L4 with a 25-gauge needle. We assessed the sensory block with a pin-prick,
      the motor block using the Bromage scale, analgesia with the visual analog scale
      and sedation with the modified Wilson scale. We also recorded the hemodynamic and
      respiratory parameters. RESULTS: The groups were demographically similar. The
      mean time of achievement of motor block (Bromage 3) and sensory block at level T9
      was significantly shorter in the BC group compared with B group (p = 0.002, p =
      0.000, respeectively). The motor block regression time was not significantly
      different between the two groups (p = 0.237). The postoperative analgesia
      requirement was significantly longer in group BC compared with group B (p =
      0.000). No neurological deficit, sedation or other significant adverse effects
      were recorded. CONCLUSION: The intrathecal application of clonidine in
      combination with bupivacaine improves the duration and quality of spinal
      anesthesia; it also provides longer duration of postoperative analgesia, without
      significant side effects.

PMID- 22396364
TI  - Variations between two 24-hour urine collections in patients presenting to a
      tertiary stone clinic.
AB  - INTRODUCTION: The current Canadian Urological Association (CUA) guideline
      recommends two 24-hour urine collections in the metabolic evaluation for patients
      with urolithiasis. The aim of the present study was to compare two consecutive 24
      hour urine collections in patients with a history of urolithiasis presenting to a
      tertiary stone clinic. METHODS: We retrospectively reviewed 188 patients who had
      two 24-hour collections upon presentation between January 2010 and December 2010.
      Samples were collected on consecutive days and examined for the following 11
      urinary parameters: volume, creatinine, sodium, calcium, uric acid, citrate,
      oxalate, potassium, phosphorous, magnesium and urea nitrogen. For each parameter,
      the absolute value of the difference between the two samples rather than the
      direct difference was compared with zero. Similarly, the percent difference
      between samples was calculated for each parameter. RESULTS: The means of the
      absolute differences between the two samples were significantly different for all
      11 urinary parameters (p < 0.0001). The percent differences for all urinary
      parameters ranged from 20.5% to 34.2%. Furthermore, 17.1% to 47.6% of patients
      had a change from a value within normal limits to an abnormal value, or vice
      versa. Significance was maintained when patients with incomplete or over
      collections were excluded. CONCLUSIONS: Significant variations among the two 24
      hour urine collections were observed in all of the 11 urinary parameters
      analyzed. This variation may change clinical decision-making in up to 47.6% of
      patients if only a single 24-hour urine collection is obtained. The present study
      supports the CUA guideline of performing two 24-hour urine collections.

PMID- 22396365
TI  - Optimizing the void.

PMID- 22396366
TI  - The autologous fascia pubovaginal sling for complicated female stress
      incontinence.
AB  - INTRODUCTION: The purpose of this study is to review our contemporary experience
      with autologous fascia pubovaginal slings (AF-PVS) in the era of the midurethral
      sling. METHODS: A retrospective review was completed to identify all patients who
      underwent an AF-PVS between 2002 and 2009. A cross-sectional questionnaire was
      used to assess postoperative urinary-specific quality of life (consisting of the
      Urogenital Distress Inventory [UDI-6] and the Incontinence Impact Questionnaires
      [IIQ-7]). RESULTS: We identified 33 patients. They had failed a median of two
      previous incontinence treatments. Of these patients, 16 (48%) had failed a
      previous midurethral sling, and of these half had experienced a significant mesh
      erosion necessitating mesh removal. Preoperative median incontinence pad usage
      was 5/day. After a median follow-up of 16 months from the time of AF-PVS, the
      median pad usage had decreased to 1/day (p = 0.003). A third of the patients had
      postoperative urgency, and only 1 patient continues to use intermittent
      catheterization. The median IIQ-7 score was 19/100, and the median UDI-6 score
      was 44/100. Overall quality of life was mixed-to-delighted in 62% of patients.
      CONCLUSIONS: The AF-PVS has reasonable outcomes in a diverse population of
      patients, despite failure of other treatment modalities.

PMID- 22396367
TI  - Is there still a role for pubovaginal slings in the treatment of SUI in the era
      of mid-urethral slings?

PMID- 22396368
TI  - Clinicopathological characteristics and treatment outcomes of adult patients with
      paratesticular rhabdomyosarcoma (PRMS): A 10-year single-centre experience.
AB  - INTRODUCTION: We report our experience with 8 consecutive adults treated for
      paratesticular rhabdomyosarcoma (RMS) at a single institution between 2000 and
      2010. METHODS: After primary surgical excision, 7 patients were classified into
      group I according to the Intergroup Rhabdomyosarcoma Study Group (IRSG)
      Postsurgical Grouping Classification, and 1 patient into group IIB.
      Retroperitoneal node dissection was not a required staging procedure. Adjuvant
      chemotherapy was administered to 7 of the 8 patients. No additional radiotherapy
      was administered. RESULTS: The median age at diagnosis was 24 years (range: 18
      60). Embryonal histology was the most common (75%) subtype. During follow-up, 3
      patients experienced local relapse and 5 distant relapse. The median progression
      free and overall survival times were 17.0 +/- 9.9 months (range: 5-31) and 27.3
      +/- 1.3 months (range: 16-58), respectively. CONCLUSION: Paratesticular RMS is an
      uncommon malignancy in adults. We confirm that patients with localized
      paratesticular RMS may have different prognoses. Retroperitoneal lymphadenectomy
      can be avoided as a treatment for paratesticular RMS after radical inguinal
      orchiectomy.

PMID- 22396369
TI  - PSA density is superior than PSA and Gleason score for adverse pathologic
      features prediction in patients with clinically localized prostate cancer.
AB  - INTRODUCTION: Prostate-specific antigen (PSA) and its kinetics have changed
      prostate cancer screening and diagnosis. The aim of the present study was to
      evaluate their value in prostate cancer prognosis by determining the predictive
      potential of PSA density for adverse pathologic features after radical
      prostatectomy, in terms of positive surgical margins (PSM), extracapsular disease
      (ECD), seminal vesicle invasion (SVI) and/or lymph node invasion (LNI), and to
      compare their predictive ability with preoperative PSA and biopsy Gleason score.
      METHODS: We retrospectively analysed 285 patients diagnosed with prostate cancer
      and underwent a retropubic radical prostatectomy for clinically localized
      disease. Data concerning preoperative PSA, biopsy Gleason score and PSA density
      were collected and analyzed. PSA density was calculated by dividing preoperative
      PSA and the pathological volume of the prostate. RESULTS: There was a significant
      difference in PSA density values between patients with PSM, ECD, SVI and LNI.
      Areas under the curve for PSA density were higher than those of PSA and Gleason
      score for all parameters of adverse pathology. In multivariate analyses, it was
      shown that PSA density and Gleason score were the only statistically significant
      predictors for PSM and ECD, PSA density and PSA for SVI and only PSA density for
      LNI. CONCLUSION: PSA density is an accurate predictor for adverse pathology
      prediction in patients undergoing radical prostatectomy. These results
      demonstrate that this parameter is useful to determine the aggressiveness of
      prostate cancer and can be used as an adjunct in predicting outcomes after
      surgery.

PMID- 22396370
TI  - PSA density: The comeback kid?

PMID- 22396371
TI  - Urologic medications and ophthalmologic side effects: a review.
AB  - Commonly prescribed urologic medications can have significant ophthalmologic side
      effects. The existing information can be conflicting. We looked at alpha-blockers
      and intraoperative floppy iris syndrome (IFIS), phosphodiesterase type 5 (PDE5)
      inhibitors and non-arteritic ischemic optic neuropathy (NAION) and lastly
      anticholinergic medications and glaucoma. There is no conclusive scientific data
      on what to do if the risk of urinary retention is low to moderate, however, we
      recommend that patients having cataract surgery should stop alpha-blocker
      medications preoperatively. If there is a high risk of urinary retention, the
      alpha-blocker should not be withheld, with the active involvement of the
      ophthalmologist. The role of using 5 alpha-reductase inhibitors (5ARIs) can be
      considered. There is no convincing evidence that PDE5 inhibitors cause non
      arteritic anterior ischemic optic neuropathy (NAION), but patients should be
      advised of the possible risk of visual loss, especially in patients with risk
      factors of ischemic heart disease. Acute angle closure glaucoma (AACG or closed
      angle glaucoma) is very rarely caused by anticholinergic medications in patients
      with narrow angle anterior eye chambers. However, these medications are safe in
      patients with open angle glaucoma or treated closed angle glaucoma. Urologists
      should inquire about the patient's glaucoma history from his/her ophthalmologist
      before starting an anticholinergic medication.

PMID- 22396372
TI  - The argument for surgical therapy for stress urinary incontinence in females.

PMID- 22396374
TI  - In memoriam.

PMID- 22396373
TI  - Conservative treatment for female stress urinary incontinence: simple, reasonable
      and safe.

PMID- 22396375
TI  - A unique representation of hypospadias in ancient Greek art.

PMID- 22396376
TI  - Scrotal lymphangiomatosis: a case report.
AB  - Lymphangiomas are benign tumours of the lymphatic system, and there are several
      reported cases of scrotal lymphangioma in the literature to date. We report a
      rare case of multilocular cutaneous lymphangiomatosis treated with surgical
      excision (total scrotectomy and reconstruction using split-thickness skin grafts
      with vacuum-assisted closure dressing).

PMID- 22396377
TI  - Metastatic signet ring cell adenocarcinoma of the bladder: responsive to
      treatment?
AB  - Signet ring cell variant of mucinous adenocarcinoma of the urinary bladder is an
      exceptionally rare urologic malignancy, generally felt to be resistant to
      chemotherapy and radiotherapy. We describe a case of this malignancy with unusual
      sites of metastasis and an unexpectedly good response to treatment.

PMID- 22396378
TI  - Vertebral osteomyelitis following transrectal ultrasound-guided biopsy of the
      prostate.
AB  - Transrectal ultrasound-guided needle biopsy of the prostate (TRUS) is a well
      tolerated and standardized procedure for the diagnosis of prostate cancer.
      Complications associated with TRUS requiring emergency room visits or hospital
      admissions are relatively low and include complications, such as a 1% risk of
      urinary retention and less than 1% chance of bacterial sepsis. Vertebral
      osteomyelitis is a rare complication of TRUS; there are 3 reported cases.
      Vertebral osteomyelitis has an insidious onset and usually resolves following
      medical intervention. We present an extremely rare case of vertebral
      osteomyelitis following TRUS, its clinical outcome and management.

PMID- 22396379
TI  - Mixed epithelial and stromal tumor of the kidney (MEST) simulating an upper tract
      TCC.
AB  - We present a rare and interesting case of a mixed epithelial and stromal tumour
      (MEST) of the kidney. The case is unique as it involves a male patient with no
      history of hormonal therapy presenting with a filling defect in the renal
      collecting system and positive urine cytology. The patient was diagnosed with
      transitional cell carcinoma of the renal pelvis and subjected to
      nephroureterectomy, which revealed a solid tumour arising from the lower calyces
      and extending into the renal pelvis and upper ureter. Pathology revealed a MEST.
      The patient was disease-free at the 6-month follow-up.

PMID- 22396380
TI  - A case of metastatic urachal adenocarcinoma treated with several different
      chemotherapeutic regimens.
AB  - Urachal cancer is a rare form of bladder cancer that arises from the urachus, a
      vestigial musculofibrous band that extends from the dome of the bladder to the
      umbilicus. Urachal cancer often presents at an advanced stage and has a dismal
      prognosis. We present a case of a young woman with urachal cancer that recurred
      rapidly post-partial cystectomy. The patient was treated with up to 6 different
      chemotherapy regimens, including an oral antiangiogenic drug as part of a
      clinical trial. Our case illustrates the aggressive nature of this disease, the
      difficulty in accessing drugs for the treatment of rare cancers and the lack of
      late stage clinical trials to help guide therapeutic decisions.

PMID- 22396381
TI  - Percutaneous drainage and sclerotherapy as definitive treatment of renal
      lymphangiomatosis.
AB  - We report the technique and outcome of percutaneous drainage and sclerotherapy as
      primary treatment of renal lymphangiomatosis. Between January and May 2009, two
      patients presenting with symptomatic renal lymphangiomatosis were treated in our
      department by a minimally invasive modality combining percutaneous drainage with
      repeated sclerotherapy. We retrospectively analysed recurrence, complications and
      patient satisfaction. In this limited case series, percutaneous drainage and
      repeated sclerotherapy proved to be safe and effective for treating renal
      lymphangiomatosis. This procedure provides a minimally invasive option for
      selected patients, potentially avoiding a surgical procedure and any risk of
      complications.

PMID- 22396382
TI  - Robotic partial cystectomy for lymphangioma of the urinary bladder in an adult
      woman.
AB  - Lymphangioma of the urinary bladder is a very rare tumour in adulthood. Robotic
      partial cystectomy is evolving for treatment of a limited number of bladder
      tumours. We describe a case of an adult woman with a bladder dome lymphangioma
      for which robotic partial cystectomy was carried out.

PMID- 22396383
TI  - Relationship between renal dysfunction and outcomes in emergency department
      patients with potential acute coronary syndromes.
AB  - OBJECTIVES: To determine whether patients with elevated creatinine who present to
      the emergency department (ED) with potential acute coronary syndrome (ACS) are at
      an increased risk of acute myocardial infarction (AMI) or 30-day cardiovascular
      (CV) events. METHODS: A secondary analysis of a cohort study of patients
      presenting to the ED with potential ACS with serum creatinine measurements.
      Research assistants collected demographics, history, symptoms, hospital course
      and 30-day follow-up. Outcomes measured were in-hospital AMI and 30-day CV events
      (death, nonfatal AMI, revascularisation). Prespecified multivariable models
      included age, gender, race and cardiac risk factors and presenting
      electrocardiogram (ECG). We used a creatinine cut-off point of 132.6 mmol/l. Data
      are presented as OR and 95% CI. RESULTS: 3451 patients were enrolled (age, 52.9+/
      13.2; 55% female patients; 64% black patients). There were 120 AMI during initial
      visit and 232 patients had 30-day CV events (43 deaths, 128 AMI, 120
      revascularisations). Creatinine values were normal in 3086 (89.4%) and abnormal
      in 365 (10.5%) patients. In multivariable models the adjusted OR (95% CI) for the
      association between abnormal creatinine and AMI was 1.43 (0.88 to 2.30) and 30
      day CV events was 1.57 (1.10 to 2.25). The odds of 30-day CV events were
      increased for patients who were older, male subjects, white, had hyperlipidaemia,
      hypertension or a history of CAD, or presented with an abnormal ECG. CONCLUSION:
      In patients with potential ACS in the ED, renal dysfunction predicts a higher
      likelihood of 30-day CV events, but not an independent predictor after
      controlling for other risk factors. It appears to be a marker of other CV risks.

PMID- 22396384
TI  - Improving paediatric pain management: introducing the 'Pain Passport'.
AB  - The 'Pain Passport' is a novel method of improving the management of pain in
      children. It consists of a leaflet carried by the patient which records serial
      pain scores. It attempts to empower patients and prompt medical and nursing staff
      to evaluate the child's pain. Preliminary audit data in support of this concept
      are encouraging.

PMID- 22396385
TI  - Impact of the introduction of emergency ultrasound to one large UK emergency
      department: the REBUS study.
AB  - AIM: Firstly, to detail the experiences of one UK training region in establishing
      an emergency ultrasound (EU) training programme and secondly, to report the
      initial 30 months of EU scanning experience. METHODS: Prospective study of all
      documented emergency department (ED) ultrasound scans. Results were extracted
      from written paper reports and/or electronically saved images. Details of scan
      date, time, type of scan, grade of operator, supervision status (whether
      supervised by a level 1 competent scanner) and whether the scan was clinical
      (performed or supervised by a level 1 operator) or training, were recorded. EU
      scans were reviewed for quality (internal quality assurance) and for diagnostic
      accuracy (external quality assurance). RESULTS: Between 14 January 2009 and 4
      July 2011, 626 scans were performed by 41 operators. 263 (42%) scans were
      completed outside of normal working hours (09:00 to 17:00). There were 251
      abdominal aorta and inferior vena cava scans (40% of all scans) and 198 focused
      assessment with sonography in trauma scans (32%). The number of scans performed
      by each operator varied widely. 87 scans (14%) were supervised but the majority
      (459; 73%) were not. 484 (77%) scans were for training purposes, 124 (20%) were
      clinical scans and the majority (401; 63%) were performed by either speciality
      registrars (ST4-6) or specialist registrars (SpR). When the three commonest types
      of scans performed were analysed, eight false positives and 11 false negatives
      were identified. Only seven of these were deemed of poor quality and none led to
      poor patient outcome. CONCLUSIONS: Since the acquisition of our ED ultrasound
      machine and the development of a quality assured training programme, on average
      20 scans per month have been performed in the ED, with no known adverse patient
      outcomes.

PMID- 22396386
TI  - Direct arylation of benzene with aryl bromides using high-temperature/high
      pressure process windows: expanding the scope of C-H activation chemistry.
AB  - A detailed investigation on the direct arylation of benzene with aryl bromides by
      using first-row transition metals under high-temperature/high-pressure (high-T/p)
      conditions is described. By employing a parallel reactor platform for rapid
      reaction screening and discovery at elevated temperatures, various
      metal/ligand/base combinations were evaluated for their ability to enable biaryl
      formation through C-H activation. The combination of cobalt(III) acetylacetonate
      and lithium bis(trimethylsilyl)amide was subjected to further process
      intensification at 200  degrees C (15 bar), allowing a significant reduction of
      the catalyst/base loading and a dramatic increase in catalytic efficiency
      (turnover frequency) by a factor of 1000 compared to traditional protocols. The
      high-throughput screening additionally identified novel nickel- and copper-based
      metal/ligand combinations that favored an amination pathway competing with C-H
      activation, with the addition of ligands, such as 1,10-phenanthroline, having a
      profound influence on the selectivity. In addition to metal-based catalysts, high
      T/p process windows were also successfully applied to transition-metal-free
      systems, utilizing 1,10-phenanthroline as organocatalyst.

PMID- 22396387
TI  - The effect of urinary incontinence on health utility and health-related quality
      of life in men following prostate surgery.
AB  - AIMS: The impact of urinary incontinence (UI) on health-related quality of life
      (HRQoL) has been less well researched in men than women and the general
      population. This study aims to assess the association between UI and HRQoL in men
      1 year after prostate surgery. METHODS: Planned secondary analysis of data from
      two parallel randomized controlled trials of active conservative treatment for UI
      in 853 men following radical prostatectomy (RP) and transurethral resection of
      the prostate (TURP). Men of any age were eligible for trial inclusion if they
      were experiencing UI 6 weeks after undergoing RP or TURP at 34 centers in the
      United Kingdom. Univariate and multivariate analysis considered associations
      between health status (SF-12 and EQ-5D) and self-reported UI. Multivariate
      analysis controlled for age, obesity, UI prior to surgery, and concomitant fecal
      incontinence. RESULTS: Mean age of 411 men in the RP trial was 62.3 years (SD
      5.7) and 442 men in the TURP trial was 68.0 (SD 7.9). Of men with UI at 6 weeks
      after surgery, 76.7% in the RP group and 63.2% in the TURP group still had UI at
      12 months. Any UI at 12 months was significantly associated with reduced HRQoL in
      the RP group and lower EQ-5D and SF-12 Mental Component Scores in the TURP group.
      CONCLUSION: Any UI is a significant factor in reduced HRQoL in men following
      prostate surgery, particularly younger men who undergo RP. Its importance to
      patients as an adverse outcome should not be underestimated.

PMID- 22396388
TI  - Risk prediction measures for case-cohort and nested case-control designs: an
      application to cardiovascular disease.
AB  - Case-cohort and nested case-control designs are often used to select an
      appropriate subsample of individuals from prospective cohort studies. Despite the
      great attention that has been given to the calculation of association estimators,
      no formal methods have been described for estimating risk prediction measures
      from these 2 sampling designs. Using real data from the Swedish Twin Registry
      (2004-2009), the authors sampled unstratified and stratified (matched) case
      cohort and nested case-control subsamples and compared them with the full cohort
      (as "gold standard"). The real biomarker (high density lipoprotein cholesterol)
      and simulated biomarkers (BIO1 and BIO2) were studied in terms of association
      with cardiovascular disease, individual risk of cardiovascular disease at 3
      years, and main prediction metrics. Overall, stratification improved efficiency,
      with stratified case-cohort designs being comparable to matched nested case
      control designs. Individual risks and prediction measures calculated by using
      case-cohort and nested case-control designs after appropriate reweighting could
      be assessed with good efficiency, except for the finely matched nested case
      control design, where matching variables could not be included in the individual
      risk estimation. In conclusion, the authors have shown that case-cohort and
      nested case-control designs can be used in settings where the research aim is to
      evaluate the prediction ability of new markers and that matching strategies for
      nested case-control designs may lead to biased prediction measures.

PMID- 22396389
TI  - Impact of age at smoking initiation, dosage, and time since quitting on
      cardiovascular disease in african americans and whites: the atherosclerosis risk
      in communities study.
AB  - Despite reportedly having less tobacco exposure compared with whites, African
      Americans account for a disproportionate number of smoking-related deaths. The
      purpose of this study was to compare the prospective associations between smoking
      and cardiovascular risk in whites and African Americans. Smoking status was
      obtained on 14,200 participants from the Atherosclerosis Risk in Communities
      Study. Incidence of cardiovascular disease (CVD) was ascertained from 1987
      through 2007. Adjusted Cox proportional hazard models were used to estimate the
      CVD incidence associated with smoking behavior. Over 17 years' follow-up, there
      were 2,777 cardiovascular events. In men, compared with never smoking, current
      smoking was independently associated with 67% (95% confidence interval (CI): 43,
      95) and 72% (95% CI: 30, 126) greater risk of CVD in whites and African
      Americans, respectively. In women, the smoking-related cardiovascular risk was
      higher: 136% (95% CI: 88, 196) and 169% (95% CI: 126, 219) in African-American
      and white women, respectively. Early age at smoking initiation was independently
      associated with increased risk among all participants irrespective of race.
      Smoking cessation during follow-up was equally beneficial in both whites and
      African Americans. African Americans who smoke incur a similar level of
      cardiovascular risk as white smokers and would derive the same benefits from
      quitting as whites.

PMID- 22396391
TI  - A spatiotemporal analysis of gait freezing and the impact of pedunculopontine
      nucleus stimulation.
AB  - Gait freezing is an episodic arrest of locomotion due to an inability to take
      normal steps. Pedunculopontine nucleus stimulation is an emerging therapy
      proposed to improve gait freezing, even where refractory to medication. However,
      the efficacy and precise effects of pedunculopontine nucleus stimulation on
      Parkinsonian gait disturbance are not established. The clinical application of
      this new therapy is controversial and it is unknown if bilateral stimulation is
      more effective than unilateral. Here, in a double-blinded study using objective
      spatiotemporal gait analysis, we assessed the impact of unilateral and bilateral
      pedunculopontine nucleus stimulation on triggered episodes of gait freezing and
      on background deficits of unconstrained gait in Parkinson's disease. Under
      experimental conditions, while OFF medication, Parkinsonian patients with severe
      gait freezing implanted with pedunculopontine nucleus stimulators below the
      pontomesencephalic junction were assessed during three conditions; off
      stimulation, unilateral stimulation and bilateral stimulation. Results were
      compared to Parkinsonian patients without gait freezing matched for disease
      severity and healthy controls. Pedunculopontine nucleus stimulation improved
      objective measures of gait freezing, with bilateral stimulation more effective
      than unilateral. During unconstrained walking, Parkinsonian patients who
      experience gait freezing had reduced step length and increased step length
      variability compared to patients without gait freezing; however, these deficits
      were unchanged by pedunculopontine nucleus stimulation. Chronic pedunculopontine
      nucleus stimulation improved Freezing of Gait Questionnaire scores, reflecting a
      reduction of the freezing encountered in patients' usual environments and
      medication states. This study provides objective, double-blinded evidence that in
      a specific subgroup of Parkinsonian patients, stimulation of a caudal
      pedunculopontine nucleus region selectively improves gait freezing but not
      background deficits in step length. Bilateral stimulation was more effective than
      unilateral.

PMID- 22396392
TI  - W R Gowers 1895: two unpublished post-graduate lectures.
AB  - On 10 May 1893, William Gowers began a series of weekly clinical demonstrations
      at the National Hospital for the Relief and Cure of the Paralysed and Epileptic
      at Queen Square, London. The contents of some of these demonstrations were
      published as 'Post-graduate Clinical Lectures' in the Clinical Journal, and in
      other learned periodicals. Some were also later included in his book Clinical
      Lectures on Diseases of the Nervous System. Recently, the manuscripts of what
      appear to be verbatim transcripts of two further but unpublished demonstrations
      from Gowers' course in 1895 came to light, one containing alterations made in
      Gowers' handwriting. The first concerned a case of disseminated sclerosis and its
      differentiation from hysterical paraplegia, the second transverse myelitis and
      its consequences for bladder function. Why these lectures were never published
      remains uncertain, but their relatively unedited contents reveal something of the
      neurological knowledge, diagnostic reasoning, clinical examination and teaching
      methods employed by one of the great pioneers of clinical neurology.

PMID- 22396390
TI  - Suppression of protein aggregation by chaperone modification of high molecular
      weight complexes.
AB  - Protein misfolding and aggregation are associated with many neurodegenerative
      diseases, including Huntington's disease. The cellular machinery for maintaining
      proteostasis includes molecular chaperones that facilitate protein folding and
      reduce proteotoxicity. Increasing the protein folding capacity of cells through
      manipulation of DNAJ chaperones has been shown to suppress aggregation and
      ameliorate polyglutamine toxicity in cells and flies. However, to date these
      promising findings have not been translated to mammalian models of disease. To
      address this issue, we developed transgenic mice that over-express the neuronal
      chaperone HSJ1a (DNAJB2a) and crossed them with the R6/2 mouse model of
      Huntington's disease. Over-expression of HSJ1a significantly reduced mutant
      huntingtin aggregation and enhanced solubility. Surprisingly, this was mediated
      through specific association with K63 ubiquitylated, detergent insoluble, higher
      order mutant huntingtin assemblies that decreased their ability to nucleate
      further aggregation. This was dependent on HSJ1a client binding ability,
      ubiquitin interaction and functional co-operation with HSP70. Importantly, these
      changes in mutant huntingtin solubility and aggregation led to improved
      neurological performance in R6/2 mice. These data reveal that prevention of
      further aggregation of detergent insoluble mutant huntingtin is an additional
      level of quality control for late stage chaperone-mediated neuroprotection.
      Furthermore, our findings represent an important proof of principle that DNAJ
      manipulation is a valid therapeutic approach for intervention in Huntington's
      disease.

PMID- 22396393
TI  - An integrative architecture for general intelligence and executive function
      revealed by lesion mapping.
AB  - Although cognitive neuroscience has made remarkable progress in understanding the
      involvement of the prefrontal cortex in executive control, the broader functional
      networks that support high-level cognition and give rise to general intelligence
      remain to be well characterized. Here, we investigated the neural substrates of
      the general factor of intelligence (g) and executive function in 182 patients
      with focal brain damage using voxel-based lesion-symptom mapping. The Wechsler
      Adult Intelligence Scale and Delis-Kaplan Executive Function System were used to
      derive measures of g and executive function, respectively. Impaired performance
      on these measures was associated with damage to a distributed network of left
      lateralized brain areas, including regions of frontal and parietal cortex and
      white matter association tracts, which bind these areas into a coordinated
      system. The observed findings support an integrative framework for understanding
      the architecture of general intelligence and executive function, supporting their
      reliance upon a shared fronto-parietal network for the integration and control of
      cognitive representations and making specific recommendations for the application
      of the Wechsler Adult Intelligence Scale and Delis-Kaplan Executive Function
      System to the study of high-level cognition in health and disease.

PMID- 22396394
TI  - Delayed treatment with chondroitinase ABC promotes sensorimotor recovery and
      plasticity after stroke in aged rats.
AB  - Stroke is the dominant cause of sensorimotor disability that primarily affects
      the elderly. We now show that neuroplasticity and functional recovery after
      stroke is constrained by inhibitory chondroitin sulphates. In two blinded,
      randomized preclinical trials, degradation of chondroitin sulphate using
      chondroitinase ABC reactivated neuroplasticity and promoted sensorimotor recovery
      after stroke in elderly rats. Three days after stroke, chondroitinase ABC was
      microinjected into the cervical spinal cord to induce localized plasticity of
      forelimb sensorimotor spinal circuitry. Chondroitinase ABC effectively removed
      chondroitin sulphate from the extracellular matrix and perineuronal nets. Three
      different tests of sensorimotor function showed that chondroitinase ABC promoted
      recovery of forelimb function. Anterograde and retrograde tracing showed that
      chondroitinase ABC also induced sprouting of the contralesional corticospinal
      tract in the aged treated hemicord. Chondroitinase ABC did not neuroprotect the
      peri-infarct region. We show for the first time delayed chondroitinase ABC
      treatment promotes neuroanatomical and functional recovery after focal ischaemic
      stroke in an elderly nervous system.

PMID- 22396395
TI  - Muscle-specific kinase myasthenia gravis IgG4 autoantibodies cause severe
      neuromuscular junction dysfunction in mice.
AB  - Myasthenia gravis is a paralytic disorder with autoantibodies against
      acetylcholine receptors at the neuromuscular junction. A proportion of patients
      instead has antibodies against muscle-specific kinase, a protein essential for
      acetylcholine receptor clustering. These are generally of the immunoglobulin-G4
      subclass and correlate with disease severity, suggesting specific myasthenogenic
      activity. However, immunoglobulin-G4 subclass antibodies are generally considered
      to be 'benign' and direct proof for their pathogenicity in muscle-specific kinase
      myasthenia gravis (or other immunoglobulin-G4-associated disorders) is lacking.
      Furthermore, the exact electrophysiological synaptic defects caused at
      neuromuscular junctions by human anti-muscle-specific kinase autoantibodies are
      hitherto unknown. We show that purified immunoglobulin-G4, but not immunoglobulin
      G1-3, from patients with muscle-specific kinase myasthenia gravis binds to mouse
      neuromuscular junctions in vitro, and that injection into immunodeficient mice
      causes paralysis. Injected immunoglobulin-G4 caused reduced density and
      fragmented area of neuromuscular junction acetylcholine receptors. Detailed
      electrophysiological synaptic analyses revealed severe reduction of postsynaptic
      acetylcholine sensitivity, and exaggerated depression of presynaptic
      acetylcholine release during high-rate activity, together causing the (fatigable)
      muscle weakness. Intriguingly, compensatory transmitter release upregulation,
      which is the normal homeostatic response in acetylcholine receptor myasthenia
      gravis, was absent. This conveys extra vulnerability to neurotransmission at
      muscle-specific kinase myasthenia gravis neuromuscular junctions. Thus, we
      demonstrate that patient anti-muscle-specific kinase immunoglobulin-G4 is
      myasthenogenic, independent of additional immune system components, and have
      elucidated the underlying electrophysiological neuromuscular junction
      abnormalities.

PMID- 22396396
TI  - Diverse aspects of vulnerability at the neuromuscular junction.

PMID- 22396398
TI  - Sex differences in the brain: the not so inconvenient truth.

PMID- 22396397
TI  - Hypokinesia without decrement distinguishes progressive supranuclear palsy from
      Parkinson's disease.
AB  - Repetitive finger tapping is commonly used to assess bradykinesia in Parkinson's
      disease. The Queen Square Brain Bank diagnostic criterion of Parkinson's disease
      defines bradykinesia as 'slowness of initiation with progressive reduction in
      speed and amplitude of repetitive action'. Although progressive supranuclear
      palsy is considered an atypical parkinsonian syndrome, it is not known whether
      patients with progressive supranuclear palsy have criteria-defined bradykinesia.
      This study objectively assessed repetitive finger tap performance and handwriting
      in patients with Parkinson's disease (n = 15), progressive supranuclear palsy (n
      = 9) and healthy age- and gender-matched controls (n = 16). The motion of the
      hand and digits was recorded in 3D during 15-s repetitive index finger-to-thumb
      tapping trials. The main finding was hypokinesia without decrement in patients
      with progressive supranuclear palsy, which differed from the finger tap pattern
      in Parkinson's disease. Average finger separation amplitude in progressive
      supranuclear palsy was less than half of that in controls and Parkinson's disease
      (P < 0.001 in both cases). Change in tap amplitude over consecutive taps was
      computed by linear regression. The average amplitude slope in progressive
      supranuclear palsy was nearly zero (0.01 degrees /cycle) indicating a lack of
      decrement, which differed from the negative slope in patients with Parkinson's
      disease OFF levodopa (-0.20 degrees /cycle, P = 0.002). 'Hypokinesia', defined as
      <50% of control group's mean amplitude, combined with 'absence of decrement',
      defined as mean positive amplitude slope, were identified in 87% of finger tap
      trials in the progressive supranuclear palsy group and only 12% in the
      Parkinson's disease OFF levodopa group. In progressive supranuclear palsy, the
      mean amplitude was not correlated with disease duration or other clinimetric
      scores. In Parkinson's disease, finger tap pattern was compatible with criteria
      defined bradykinesia, characterized by slowness with progressive reduction in
      amplitude and speed and increased variability in speed throughout the tap trial.
      In Parkinson's disease, smaller amplitude, slower speed and greater speed
      variability were all associated with a more severe Unified Parkinson's Disease
      Rating Scale motor score. Analyses of handwriting showed that micrographia,
      defined as smaller than 50% of the control group's mean script size, was present
      in 75% of patients with progressive supranuclear palsy and 15% of patients with
      Parkinson's disease (P = 0.022). Most scripts performed by patients with
      progressive supranuclear palsy did not exhibit decrements in script size. In
      conclusion, patients with progressive supranuclear palsy have a specific finger
      tap pattern of 'hypokinesia without decrement' and they do not have criteria
      defined limb bradykinesia. Similarly, 'micrographia' and 'lack of decrement in
      script size' are also more common in progressive supranuclear palsy than in
      Parkinson's disease.

PMID- 22396399
TI  - Extending the study of decision values to cases where options are presented using
      different sensory modalities.

PMID- 22396400
TI  - Memory erasure, enhanced extinction and disrupted reconsolidation.

PMID- 22396401
TI  - Tamalin is a critical mediator of electroconvulsive shock-induced adult
      neuroplasticity.
AB  - The molecular mechanisms underlying the effects of electroconvulsive shock (ECS)
      therapy, a fast-acting and very effective antidepressant therapy, are poorly
      understood. Changes related to neuroplasticity, including enhanced adult
      hippocampal neurogenesis and neuronal arborization, are believed to play an
      important role in mediating the effects of ECS. Here we show a dynamic
      upregulation of the scaffold protein tamalin, selectively in the hippocampus of
      animals subjected to ECS. Interestingly, this gene upregulation is functionally
      significant because tamalin deletion in mice abrogated ECS-induced neurogenesis
      in the adult mouse hippocampus. Furthermore, loss of tamalin blunts mossy fiber
      sprouting and dendritic arborization caused by ECS. These data suggest an
      essential role for tamalin in ECS-induced adult neuroplasticity and provide new
      insight into the pathways that are involved in mediating ECS effects.

PMID- 22396402
TI  - Restoration of synaptic plasticity and learning in young and aged NCAM-deficient
      mice by enhancing neurotransmission mediated by GluN2A-containing NMDA receptors.
AB  - Neural cell adhesion molecule (NCAM) is the predominant carrier of the unusual
      glycan polysialic acid (PSA). Deficits in PSA and/or NCAM expression cause
      impairments in hippocampal long-term potentiation and depression (LTP and LTD)
      and are associated with schizophrenia and aging. In this study, we show that
      impaired LTP in adult NCAM-deficient (NCAM(-/-)) mice is restored by increasing
      the activity of the NMDA subtype of glutamate receptor (GluN) through either
      reducing the extracellular Mg2+ concentration or applying d-cycloserine (DCS), a
      partial agonist of the GluN glycine binding site. Pharmacological inhibition of
      the GluN2A subtype reduced LTP to the same level in NCAM(-/-) and wild-type
      (NCAM(+/+)) littermate mice and abolished the rescue by DCS in NCAM(-/-) mice,
      suggesting that the effects of DCS are mainly mediated by GluN2A. The
      insufficient contribution of GluN to LTD in NCAM(-/-) mice was also compensated
      for by DCS. Furthermore, impaired contextual and cued fear conditioning levels
      were restored in NCAM(-/-) mice by administration of DCS before conditioning. In
      12-month-old NCAM(-/-), but not NCAM(+/+) mice, there was a decline in LTP
      compared with 3-month-old mice that could be rescued by DCS. In 24-month-old mice
      of both genotypes, there was a reduction in LTP that could be fully restored by
      DCS in NCAM(+/+) mice but only partially restored in NCAM(-/-) mice. Thus,
      several deficiencies of NCAM(-/-) mice can be ameliorated by enhancing GluN2A
      mediated neurotransmission with DCS.

PMID- 22396403
TI  - Deliberation in the motor system: reflex gains track evolving evidence leading to
      a decision.
AB  - Both decision making and sensorimotor control require real-time processing of
      noisy information streams. Historically these processes were thought to operate
      sequentially: cognitive processing leads to a decision, and the outcome is passed
      to the motor system to be converted into action. Recently, it has been suggested
      that the decision process may provide a continuous flow of information to the
      motor system, allowing it to prepare in a graded fashion for the probable
      outcome. Such continuous flow is supported by electrophysiology in nonhuman
      primates. Here we provide direct evidence for the continuous flow of an evolving
      decision variable to the motor system in humans. Subjects viewed a dynamic random
      dot display and were asked to indicate their decision about direction by moving a
      handle to one of two targets. We probed the state of the motor system by
      perturbing the arm at random times during decision formation. Reflex gains were
      modulated by the strength and duration of motion, reflecting the accumulated
      evidence in support of the evolving decision. The magnitude and variance of these
      gains tracked a decision variable that explained the subject's decision accuracy.
      The findings support a continuous process linking the evolving computations
      associated with decision making and sensorimotor control.

PMID- 22396404
TI  - Incorporating cross-modal statistics in the development and maintenance of
      multisensory integration.
AB  - Development of multisensory integration capabilities in superior colliculus (SC)
      neurons was examined in cats whose visual-auditory experience was restricted to a
      circumscribed period during early life (postnatal day 30-8 months). Animals were
      periodically exposed to visual and auditory stimuli appearing either randomly in
      space and time, or always in spatiotemporal concordance. At all other times
      animals were maintained in darkness. Physiological testing was initiated at ~2
      years of age. Exposure to random visual and auditory stimuli proved insufficient
      to spur maturation of the ability to integrate cross-modal stimuli, but exposure
      to spatiotemporally concordant cross-modal stimuli was highly effective. The
      multisensory integration capabilities of neurons in the latter group resembled
      those of normal animals and were retained for >16 months in the absence of
      subsequent visual-auditory experience. Furthermore, the neurons were capable of
      integrating stimuli having physical properties differing significantly from those
      in the exposure set. These observations suggest that acquiring the rudiments of
      multisensory integration requires little more than exposure to consistent
      relationships between the modality-specific components of a cross-modal event,
      and that continued experience with such events is not necessary for their
      maintenance. Apparently, the statistics of cross-modal experience early in life
      define the spatial and temporal filters that determine whether the components of
      cross-modal stimuli are to be integrated or treated as independent events, a
      crucial developmental process that determines the spatial and temporal rules by
      which cross-modal stimuli are integrated to enhance both sensory salience and the
      likelihood of eliciting an SC-mediated motor response.

PMID- 22396405
TI  - Causal links between dorsal medial superior temporal area neurons and
      multisensory heading perception.
AB  - The dorsal medial superior temporal area (MSTd) in the extrastriate visual cortex
      is thought to play an important role in heading perception because neurons in
      this area are tuned to both optic flow and vestibular signals. MSTd neurons also
      show significant correlations with perceptual judgments during a fine heading
      direction discrimination task. To test for a causal link with heading perception,
      we used microstimulation and reversible inactivation techniques to artificially
      perturb MSTd activity while monitoring behavioral performance. Electrical
      microstimulation significantly biased monkeys' heading percepts based on optic
      flow, but did not significantly impact vestibular heading judgments. The latter
      result may be due to the fact that vestibular heading preferences in MSTd are
      more weakly clustered than visual preferences and multiunit tuning for vestibular
      stimuli is weak. Reversible chemical inactivation, however, increased behavioral
      thresholds when heading judgments were based on either optic flow or vestibular
      cues, although the magnitude of the effects was substantially stronger for optic
      flow. Behavioral deficits in a combined visual/vestibular stimulus condition were
      intermediate between the single-cue effects. Despite deficits in discrimination
      thresholds, animals were able to combine visual and vestibular cues near
      optimally, even after large bilateral muscimol injections into MSTd. Simulations
      show that the overall pattern of results following inactivation is consistent
      with a mixture of contributions from MSTd and other areas with vestibular
      dominant tuning for heading. Our results support a causal link between MSTd
      neurons and multisensory heading perception but suggest that other multisensory
      brain areas also contribute.

PMID- 22396406
TI  - Arg kinase regulates prefrontal dendritic spine refinement and cocaine-induced
      plasticity.
AB  - Adolescence is characterized by vulnerability to the development of
      neuropsychiatric disorders including drug addiction, as well as prefrontal
      cortical refinement that culminates in structural stability in adulthood.
      Neuronal refinement and stabilization are hypothesized to confer resilience to
      poor decision making and addictive-like behaviors, although intracellular
      mechanisms are largely unknown. We characterized layer V prefrontal dendritic
      spine development and refinement in adolescent wild-type mice and mice lacking
      the cytoskeletal regulatory protein Abl-related gene (Arg) kinase. Relative to
      hippocampal CA1 pyramidal neurons, which exhibited a nearly linear increase in
      spine density up to postnatal day 60 (P60), wild-type prefrontal spine density
      peaked at P31, and then declined by 18% by P56-P60. In contrast, dendritic spines
      in mice lacking Arg destabilized by P31, leading to a net loss in both
      structures. Destabilization corresponded temporally to the emergence of
      exaggerated psychomotor sensitivity to cocaine. Moreover, cocaine reduced
      dendritic spine density in wild-type orbitofrontal cortex and enlarged remaining
      spine heads, but arg(-/-) spines were unresponsive. Local application of Arg or
      actin polymerization inhibitors exaggerated cocaine sensitization, as did reduced
      gene dosage of the Arg substrate, p190RhoGAP. Genetic and pharmacological Arg
      inhibition also retarded instrumental reversal learning and potentiated
      responding for reward-related cues, providing evidence that Arg regulates both
      psychomotor sensitization and decision-making processes implicated in addiction.
      These findings also indicate that structural refinement in the adolescent
      orbitofrontal cortex mitigates psychostimulant sensitivity and support the
      emerging perspective that the structural response to cocaine may, at any age,
      have behaviorally protective consequences.

PMID- 22396408
TI  - Bias in the brain: a diffusion model analysis of prior probability and potential
      payoff.
AB  - In perceptual decision-making, advance knowledge biases people toward choice
      alternatives that are more likely to be correct and more likely to be profitable.
      Accumulation-to-bound models provide two possible explanations for these effects:
      prior knowledge about the relative attractiveness of the alternatives at hand
      changes either the starting point of the decision process, or the rate of
      evidence accumulation. Here, we used model-based functional MRI to investigate
      whether these effects are similar for different types of prior knowledge, and
      whether there is a common neural substrate underlying bias in simple perceptual
      choices. We used two versions of the random-dot motion paradigm in which we
      manipulated bias by: (1) changing the prior likelihood of occurrence for two
      alternatives ("prior probability") and (2) assigning a larger reward to one of
      two alternatives ("potential payoff"). Human subjects performed the task inside
      and outside a 3T MRI scanner. For each manipulation, bias was quantified by
      fitting the drift diffusion model to the behavioral data. Individual measurements
      of bias were then used in the imaging analyses to identify regions involved in
      biasing choice behavior. Behavioral results showed that subjects tended to make
      more and faster choices toward the alternative that was most probable or had the
      largest payoff. This effect was primarily due to a change in the starting point
      of the accumulation process. Imaging results showed that, at cue level, regions
      of the frontoparietal network are involved in changing the starting points in
      both manipulations, suggesting a common mechanism underlying the biasing effects
      of prior knowledge.

PMID- 22396407
TI  - Biglycan is an extracellular MuSK binding protein important for synapse
      stability.
AB  - The receptor tyrosine kinase MuSK is indispensable for nerve-muscle synapse
      formation and maintenance. MuSK is necessary for prepatterning of the endplate
      zone anlage and as a signaling receptor for agrin-mediated postsynaptic
      differentiation. MuSK-associated proteins such as Dok7, LRP4, and Wnt11r are
      involved in these early events in neuromuscular junction formation. However, the
      mechanisms regulating synapse stability are poorly understood. Here we examine a
      novel role for the extracellular matrix protein biglycan in synapse stability.
      Synaptic development in fetal and early postnatal biglycan null (bgn(-/o)) muscle
      is indistinguishable from wild-type controls. However, by 5 weeks after birth,
      nerve-muscle synapses in bgn(-/o) mice are abnormal as judged by the presence of
      perijunctional folds, increased segmentation, and focal misalignment of
      acetylcholinesterase and AChRs. These observations indicate that previously
      occupied presynaptic and postsynaptic territory has been vacated. Biglycan binds
      MuSK and the levels of this receptor tyrosine kinase are selectively reduced at
      bgn(-/o) synapses. In bgn(-/o) myotubes, the initial stages of agrin-induced MuSK
      phosphorylation and AChR clustering are normal, but the AChR clusters are
      unstable. This stability defect can be substantially rescued by the addition of
      purified biglycan. Together, these results indicate that biglycan is an
      extracellular ligand for MuSK that is important for synapse stability.

PMID- 22396409
TI  - Hippocampal histone acetylation regulates object recognition and the estradiol
      induced enhancement of object recognition.
AB  - Histone acetylation has recently been implicated in learning and memory
      processes, yet necessity of histone acetylation for such processes has not been
      demonstrated using pharmacological inhibitors of histone acetyltransferases
      (HATs). As such, the present study tested whether garcinol, a potent HAT
      inhibitor in vitro, could impair hippocampal memory consolidation and block the
      memory-enhancing effects of the modulatory hormone 17beta-estradiol E2. We first
      showed that bilateral infusion of garcinol (0.1, 1, or 10 MUg/side) into the
      dorsal hippocampus (DH) immediately after training impaired object recognition
      memory consolidation in ovariectomized female mice. A behaviorally effective dose
      of garcinol (10 MUg/side) also significantly decreased DH HAT activity. We next
      examined whether DH infusion of a behaviorally subeffective dose of garcinol (1
      ng/side) could block the effects of DH E2 infusion on object recognition and
      epigenetic processes. Immediately after training, ovariectomized female mice
      received bilateral DH infusions of vehicle, E2 (5 MUg/side), garcinol (1
      ng/side), or E2 plus garcinol. Forty-eight hours later, garcinol blocked the
      memory-enhancing effects of E2. Garcinol also reversed the E2-induced increase in
      DH histone H3 acetylation, HAT activity, and levels of the de novo
      methyltransferase DNMT3B, as well as the E2-induced decrease in levels of the
      memory repressor protein histone deacetylase 2. Collectively, these findings
      suggest that histone acetylation is critical for object recognition memory
      consolidation and the beneficial effects of E2 on object recognition.
      Importantly, this work demonstrates that the role of histone acetylation in
      memory processes can be studied using a HAT inhibitor.

PMID- 22396410
TI  - Striatal alpha5 nicotinic receptor subunit regulates dopamine transmission in
      dorsal striatum.
AB  - Polymorphisms in the gene for the alpha5 nicotinic acetylcholine receptor (nAChR)
      subunit are associated with vulnerability to nicotine addiction. However, the
      underlying normal functions of alpha5-containing nAChRs in the brain are poorly
      understood. Striatal dopamine (DA) transmission is critical to the acquisition
      and maintenance of drug addiction and is modulated strongly by nicotine acting at
      heteromeric beta2-containing (beta2*) nAChRs. We explored whether alpha5
      subunits, as well as alpha4, alpha6, and beta3 subunits, participate in the
      powerful regulation of DA release probability by beta2* nAChRs in nucleus
      accumbens (NAc) core and in dorsal striatum [caudatoputamen (CPu)]. We detected
      evoked dopamine release using fast-scan cyclic voltammetry at carbon-fiber
      microelectrodes in striatal slices from mice with deletions of alpha4, alpha5,
      alpha6, or beta3 subunits. We show that the nAChR subtypes that dominantly
      regulate dopamine transmission depend critically upon alpha5 subunits in the
      dorsal CPu in alpha4alpha5(non-alpha6)beta2-nAChRs but not in NAc core, where
      alpha4alpha6beta2beta3-nAChRs are required. These data reveal the distinct
      populations of nAChRs that govern DA transmission in NAc core versus dorsal CPu.
      Furthermore, they indicate that alpha5 subunits are critical to the regulation of
      DA transmission by alpha4beta2* nAChRs in regions of striatum associated with
      habitual and instrumental responses (dorsal CPu) rather than pavlovian
      associations (NAc).

PMID- 22396411
TI  - Mechanisms underlying signal filtering at a multisynapse contact.
AB  - Visual information must be relayed through the lateral geniculate nucleus before
      it reaches the visual cortex. However, not all spikes created in the retina lead
      to postsynaptic spikes and properties of the retinogeniculate synapse contribute
      to this filtering. To understand the mechanisms underlying this filtering
      process, we conducted electrophysiology to assess the properties of signal
      transmission in the Long-Evans rat. We also performed SDS-digested freeze
      fracture replica labeling to quantify the receptor and transporter distribution,
      as well as EM reconstruction to describe the 3D structure. To analyze the impact
      of transmitter diffusion on the activity of the receptors, simulations were
      integrated. We identified that a large contributor to the filtering is the marked
      paired-pulse depression at this synapse, which was intensified by the
      morphological characteristics of the contacts. The broad presynaptic and
      postsynaptic contact area restricts transmitter diffusion two dimensionally.
      Additionally, the presence of multiple closely arranged release sites invites
      intersynaptic spillover, which causes desensitization of AMPA receptors. The
      presence of AMPA receptors that slowly recover from desensitization along with
      the high presynaptic release probability and multivesicular release at each
      synapse also contribute to the depression. These features contrast with many
      other synapses where spatiotemporal spread of transmitter is limited by rapid
      transmitter clearance allowing synapses to operate more independently. We propose
      that the micrometer-order structure can ultimately affect the visual information
      processing.

PMID- 22396412
TI  - Neurosilence: profound suppression of neural activity following intracerebral
      administration of the protein synthesis inhibitor anisomycin.
AB  - Early in their formation, memories are thought to be labile, requiring a process
      called consolidation to give them near-permanent stability. Evidence for
      consolidation as an active and biologically separate mnemonic process has been
      established through posttraining manipulations of the brain that promote or
      disrupt subsequent retrieval. Consolidation is thought to be ultimately mediated
      via protein synthesis since translational inhibitors such as anisomycin disrupt
      subsequent memory when administered in a critical time window just following
      initial learning. However, when applied intracerebrally, they may induce
      additional neural disturbances. Here, we report that intrahippocampal
      microinfusions of anisomycin in urethane-anesthetized rats at dosages previously
      used in memory consolidation studies strongly suppressed (and in some cases
      abolished) spontaneous and evoked local field potentials (and associated
      extracellular current flow) as well as multiunit activity. These effects were not
      coupled to the production of pathological electrographic activity nor were they
      due to cell death. However, the amount of suppression was correlated with the
      degree of protein synthesis inhibition as measured by autoradiography and was
      also observed with cycloheximide, another translational inhibitor. Our results
      suggest that (1) the amnestic effects of protein synthesis inhibitors are
      confounded by neural silencing and that (2) intact protein synthesis is crucial
      for neural signaling itself.

PMID- 22396413
TI  - Role of neurokinin B in the control of female puberty and its modulation by
      metabolic status.
AB  - Human genetic studies have revealed that neurokinin B (NKB) and its receptor,
      neurokinin-3 receptor (NK3R), are essential elements for normal reproduction;
      however, the precise role of NKB-NK3R signaling in the initiation of puberty
      remains unknown. We investigated here the regulation of Tac2 and Tacr3 mRNAs
      (encoding NKB and NK3R, respectively) in female rats and demonstrated that their
      hypothalamic expression is increased along postnatal maturation. At puberty, both
      genes were widely expressed throughout the brain, including the lateral
      hypothalamic area and the arcuate nucleus (ARC)/medial basal hypothalamus, where
      the expression of Tacr3 increased across pubertal transition. We showed that
      central administration of senktide (NK3R agonist) induced luteinizing hormone
      (LH) secretion in prepubertal and peripubertal females. Conversely, chronic
      infusion of an NK3R antagonist during puberty moderately delayed the timing of
      vaginal opening (VO) and tended to decrease LH levels. The expression of NKB and
      its receptor was sensitive to changes in metabolic status during puberty, as
      reflected by a reduction in Tacr3 (and, to a lesser extent, Tac2) expression in
      the ARC after a 48 h fast. Yet, acute LH responses to senktide in pubertal
      females were preserved, if not augmented, under fasting conditions, suggesting
      sensitization of the NKB-NK3R-gonadotropin-releasing hormone signaling pathway
      under metabolic distress. Moreover, repeated administration of senktide to female
      rats with pubertal arrest due to chronic undernutrition rescued VO (in ~50% of
      animals) and potently elicited LH release. Altogether, our observations suggest
      that NKB-NK3R signaling plays a role in pubertal maturation and that its
      alterations may contribute to pubertal disorders linked to metabolic stress and
      negative energy balance.

PMID- 22396414
TI  - Striatal D2 receptors regulate dendritic morphology of medium spiny neurons via
      Kir2 channels.
AB  - Structural plasticity in the adult brain is essential for adaptive behaviors and
      is thought to contribute to a variety of neurological and psychiatric disorders.
      Medium spiny neurons of the striatum show a high degree of structural plasticity
      that is modulated by dopamine through unknown signaling mechanisms. Here, we
      demonstrate that overexpression of dopamine D2 receptors in medium spiny neurons
      increases their membrane excitability and decreases the complexity and length of
      their dendritic arbors. These changes can be reversed in the adult animal after
      restoring D2 receptors to wild-type levels, demonstrating a remarkable degree of
      structural plasticity in the adult striatum. Increased excitability and decreased
      dendritic arborization are associated with downregulation of inward rectifier
      potassium channels (Kir2.1/2.3). Downregulation of Kir2 function is critical for
      the neurophysiological and morphological changes in vivo because virally mediated
      expression of a dominant-negative Kir2 channel is sufficient to recapitulate the
      changes in D2 transgenic mice. These findings may have important implications for
      the understanding of basal ganglia disorders, and more specifically
      schizophrenia, in which excessive activation of striatal D2 receptors has long
      been hypothesized to be of pathophysiologic significance.

PMID- 22396416
TI  - Spatial updating depends on gaze direction even after loss of vision.
AB  - Direction of gaze (eye angle + head angle) has been shown to be important for
      representing space for action, implying a crucial role of vision for spatial
      updating. However, blind people have no access to vision yet are able to perform
      goal-directed actions successfully. Here, we investigated the role of visual
      experience for localizing and updating targets as a function of intervening gaze
      shifts in humans. People who differed in visual experience (late blind,
      congenitally blind, or sighted) were briefly presented with a proprioceptive
      reach target while facing it. Before they reached to the target's remembered
      location, they turned their head toward an eccentric direction that also induced
      corresponding eye movements in sighted and late blind individuals. We found that
      reaching errors varied systematically as a function of shift in gaze direction
      only in participants with early visual experience (sighted and late blind). In
      the late blind, this effect was solely present in people with moveable eyes but
      not in people with at least one glass eye. Our results suggest that the effect of
      gaze shifts on spatial updating develops on the basis of visual experience early
      in life and remains even after loss of vision as long as feedback from the eyes
      and head is available.

PMID- 22396415
TI  - The BDNF Val66Met polymorphism impairs synaptic transmission and plasticity in
      the infralimbic medial prefrontal cortex.
AB  - The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is a common
      human single nucleotide polymorphism (SNP) that affects the regulated release of
      BDNF, and has been implicated in affective disorders and cognitive dysfunction. A
      decreased activation of the infralimbic medial prefrontal cortex (IL-mPFC), a
      brain region critical for the regulation of affective behaviors, has been
      described in BDNF(Met) carriers. However, it is unclear whether and how the
      Val66Met polymorphism affects the IL-mPFC synapses. Here, we report that spike
      timing-dependent plasticity (STDP) was absent in the IL-mPFC pyramidal neurons
      from BDNF(Met/Met) mice, a mouse that recapitulates the specific phenotypic
      properties of the human BDNF Val66Met polymorphism. Also, we observed a decrease
      in NMDA and GABA receptor-mediated synaptic transmission in the pyramidal neurons
      of BDNF(Met/Met) mice. While BDNF enhanced non-NMDA receptor transmission and
      depressed GABA receptor transmission in the wild-type mice, both effects were
      absent in BDNF(Met/Met) mice after BDNF treatment. Indeed, exogenous BDNF
      reversed the deficits in STDP and NMDA receptor transmission in BDNF(Met/Met)
      neurons. BDNF-mediated selective reversal of the deficit in plasticity and NMDA
      receptor transmission, but its lack of effect on GABA and non-NMDA receptor
      transmission in BDNF(Met/Met) mice, suggests separate mechanisms of Val66Met
      polymorphism upon synaptic transmission. The effect of the Val66Met polymorphism
      on synaptic transmission and plasticity in the IL-mPFC represents a mechanism to
      account for this impact of SNP on affective disorders and cognitive dysfunction.

PMID- 22396417
TI  - Regulation of mitochondrial transport and inter-microtubule spacing by tau
      phosphorylation at the sites hyperphosphorylated in Alzheimer's disease.
AB  - The microtubule-associated protein Tau is a major component of the
      neurofibrillary tangles that serve as a neuropathological hallmark of Alzheimer's
      disease. Tau is a substrate for protein phosphorylation at multiple sites and
      occurs in tangles in a hyperphosphorylated state. However, the physiological
      functions of Tau phosphorylation or how it may contribute mechanistically to
      Alzheimer's pathophysiology are not completely understood. Here, we examined the
      function of human Tau phosphorylation at three sites, Ser199, Ser202, and Thr205,
      which together comprise the AT8 sites that mark abnormal phosphorylation in
      Alzheimer's disease. Overexpression of wild-type Tau or mutated forms in which
      these sites had been changed to either unphosphorylatable alanines or
      phosphomimetic aspartates inhibited mitochondrial movement in the neurite
      processes of PC12 cells as well as the axons of mouse brain cortical neurons.
      However, the greatest effects on mitochondrial translocation were induced by
      phosphomimetic mutations. These mutations also caused expansion of the space
      between microtubules in cultured cells when membrane tension was reduced by
      disrupting actin filaments. Thus, Tau phosphorylation at the AT8 sites may have
      meaningful effects on mitochondrial movement, likely by controlling microtubule
      spacing. Hyperphosphorylation of the AT8 sites may contribute to axonal
      degeneration by disrupting mitochondrial transport in Alzheimer's disease.

PMID- 22396418
TI  - Hierarchical processing of face viewpoint in human visual cortex.
AB  - The ability to recognize objects across different viewpoints (view invariance) is
      a remarkable property of the primate visual system. According to a prominent
      theory, view information is represented by view-selective mechanisms at early
      stages of visual processing and gradually becomes view invariant in high-level
      visual areas. Single-cell recording studies have also reported an intermediate
      step of partial view invariance for mirror-symmetric face views. Nevertheless,
      similar evidence for this type of hierarchical processing for face view has not
      been reported yet in the human visual cortex. The present functional magnetic
      resonance imaging study used state-of-the-art multivariate pattern analysis to
      explore face-view tuning in the human visual cortex. Our results revealed that
      consistent with a view-selective representation, face view can be successfully
      decoded in face and object-selective regions as well as in early visual cortex.
      Critically, similar neural representations for mirror-symmetric views were found
      in high-level but not in low-level visual areas. Our results support the notion
      of gradual emergence of view-invariant representation with invariance for mirror
      symmetric images as an intermediate step and propose putative neural correlates
      of mirror-image confusion in the human brain.

PMID- 22396419
TI  - Neuronal activity in the human subthalamic nucleus encodes decision conflict
      during action selection.
AB  - The subthalamic nucleus (STN), which receives excitatory inputs from the cortex
      and has direct connections with the inhibitory pathways of the basal ganglia, is
      well positioned to efficiently mediate action selection. Here, we use
      microelectrode recordings captured during deep brain stimulation surgery as
      participants engage in a decision task to examine the role of the human STN in
      action selection. We demonstrate that spiking activity in the STN increases when
      participants engage in a decision and that the level of spiking activity
      increases with the degree of decision conflict. These data implicate the STN as
      an important mediator of action selection during decision processes.

PMID- 22396420
TI  - Role of amygdala central nucleus in aversive learning produced by shock or by
      unexpected omission of food.
AB  - Many psychological learning theories have noted commonalities between aversive
      states produced by presentation of negative reinforcers, such as electric shock,
      and the omission of expected positive reinforcers, such as food. Here, three
      groups of rats received training with one auditory cue paired with shock and
      another with the omission of expected food, a shock-paired cue and a food
      omission control cue, or a food-omission cue and a shock control cue. Food
      omission cues were established by contrast with food delivery; after extensive
      light-food pairings, the light was followed by the food-omission cue instead of
      food. Aversiveness of the food-omission cue was assessed with a conditioned
      punishment procedure, in which presentation of that cue was made contingent on
      performance of one previously trained instrumental response, whereas a second
      response had no consequences. We found that rats with lesions of amygdala central
      nucleus (CeA) showed impaired acquisition of freezing to the cue paired with
      shock and no evidence for acquisition of aversive properties by the cue that
      accompanied the omission of expected food. Furthermore, analyses of Arc and
      Homer1a mRNAs after rats were exposed to a two-epoch test procedure that allowed
      assessment of gene expression produced by two different test stimuli showed that
      both food-omission and shock-paired cues generated more neuronal activity in CeA
      than appropriate control cues. However, the number of neurons that were activated
      by both shock and food-omission cues was not significantly greater than expected
      by chance. Thus, under these test conditions, different subsets of CeA neurons
      represented these two aversive states.

PMID- 22396421
TI  - Temporal convergence of dynamic cell assemblies in the striato-pallidal network.
AB  - The basal ganglia (BG) have been hypothesized to implement a reinforcement
      learning algorithm. However, it is not clear how information is processed along
      this network, thus enabling it to perform its functional role. Here we present
      three different encoding schemes of visual cues associated with rewarding,
      neutral, and aversive outcomes by BG neuronal populations. We studied the
      response profile and dynamical behavior of two populations of projection neurons
      [striatal medium spiny neurons (MSNs), and neurons in the external segment of the
      globus pallidus (GPe)], and one neuromodulator group [striatal tonically active
      neurons (TANs)] from behaving monkeys. MSNs and GPe neurons displayed sustained
      average activity to cue presentation. The population average response of MSNs was
      composed of three distinct response groups that were temporally differentiated
      and fired in serial episodes along the trial. In the GPe, the average sustained
      response was composed of two response groups that were primarily differentiated
      by their immediate change in firing rate direction. However, unlike MSNs, neurons
      in both GPe response groups displayed prolonged and temporally overlapping
      persistent activity. The putamen TANs stereotyped response was characterized by a
      single transient response group. Finally, the MSN and GPe response groups
      reorganized at the outcome epoch, as different task events were reflected in
      different response groups. Our results strengthen the functional separation
      between BG neuromodulators and main axis neurons. Furthermore, they reveal
      dynamically changing cell assemblies in the striatal network of behaving
      primates. Finally, they support the functional convergence of the MSN response
      groups onto GPe cells.

PMID- 22396422
TI  - Stabilization of GABA(A) receptors at endocytic zones is mediated by an AP2
      binding motif within the GABA(A) receptor beta3 subunit.
AB  - The strength of synaptic inhibition can be controlled by the stability and
      endocytosis of surface and synaptic GABA(A) receptors (GABA(A)Rs), but the
      surface receptor dynamics that underpin GABA(A)R recruitment to dendritic
      endocytic zones (EZs) have not been investigated. Stabilization of GABA(A)Rs at
      EZs is likely to be regulated by receptor interactions with the clathrin-adaptor
      AP2, but the molecular determinants of these associations remain poorly
      understood. Moreover, although surface GABA(A)R downmodulation plays a key role
      in pathological disinhibition in conditions such as ischemia and epilepsy,
      whether this occurs in an AP2-dependent manner also remains unclear. Here we
      report the characterization of a novel motif containing three arginine residues
      (405RRR407) within the GABA(A)R beta3-subunit intracellular domain (ICD),
      responsible for the interaction with AP2 and GABA(A)R internalization. When this
      motif is disrupted, binding to AP2 is abolished in vitro and in rat brain. Using
      single-particle tracking, we reveal that surface beta3-subunit-containing
      GABA(A)Rs exhibit highly confined behavior at EZs, which is dependent on AP2
      interactions via this motif. Reduced stabilization of mutant GABA(A)Rs at EZs
      correlates with their reduced endocytosis and increased steady-state levels at
      synapses. By imaging wild-type or mutant super-ecliptic pHluorin-tagged GABA(A)Rs
      in neurons, we also show that, under conditions of oxygen-glucose deprivation to
      mimic cerebral ischemia, GABA(A)Rs are depleted from synapses in dendrites,
      depending on the 405RRR407 motif. Thus, AP2 binding to an RRR motif in the
      GABA(A)R beta3-subunit ICD regulates GABA(A)R residency time at EZs, steady-state
      synaptic receptor levels, and pathological loss of GABA(A)Rs from synapses during
      simulated ischemia.

PMID- 22396423
TI  - Transition to seizure: ictal discharge is preceded by exhausted presynaptic GABA
      release in the hippocampal CA3 region.
AB  - How the brain transitions into a seizure is poorly understood. Recurrent seizure
      like events (SLEs) in low-Mg2+/ high-K+ perfusate were measured in the CA3 region
      of the intact mouse hippocampus. The SLE was divided into a "preictal phase,"
      which abruptly turns into a higher frequency "ictal" phase. Blockade of GABA(A)
      receptors shortened the preictal phase, abolished interictal bursts, and
      attenuated the slow preictal depolarization, with no effect on the ictal
      duration, whereas SLEs were blocked by glutamate receptor blockade. In CA3
      pyramidal cells and stratum oriens non-fast-spiking and fast-spiking
      interneurons, recurrent GABAergic IPSCs predominated interictally and during the
      early preictal phase, synchronous with extracellularly measured recurrent field
      potentials (FPs). These IPSCs then decreased to zero or reversed polarity by the
      onset of the higher-frequency ictus. However, postsynaptic muscimol-evoked
      GABA(A) responses remained intact. Simultaneously, EPSCs synchronous with the FPs
      markedly increased to a maximum at the ictal onset. The reversal potential of the
      compound postsynaptic currents (combined simultaneous EPSCs and IPSCs) became
      markedly depolarized during the preictal phase, whereas the muscimol-evoked
      GABA(A) reversal potential remained unchanged. During the late preictal phase,
      interneuronal excitability was high, but IPSCs, evoked by local stimulation, or
      osmotically by hypertonic sucrose application, were diminished, disappearing at
      the ictal onset. We conclude that the interictal and early preictal states are
      dominated by GABAergic activity, with the onset of the ictus heralded by
      exhaustion of presynaptic release of GABA, and unopposed increased glutamatergic
      responses.

PMID- 22396424
TI  - Local dendrodendritic inhibition regulates fast synaptic transmission in visual
      thalamus.
AB  - Inhibition from thalamic interneurons plays a critical role in modulating
      information transfer between thalamus and neocortex. Interestingly, these neurons
      yield inhibition via two distinct outputs: presynaptic dendrites that innervate
      thalamocortical relay neurons and axonal outputs. Since the dendrites of thalamic
      interneurons are the primary targets of incoming synaptic information, it has
      been hypothesized that local synaptic input could produce highly focused
      dendritic output. To gain additional insight into the computational power of
      these presynaptic dendrites, we have combined two-photon laser scanning
      microscopy, glutamate uncaging, and whole-cell electrophysiological recordings to
      locally activate dendritic terminals and study their inhibitory contribution to
      rat thalamocortical relay neurons. Our findings demonstrate that local dendritic
      release from thalamic interneurons is controlled locally by AMPA/NMDA receptor
      mediated recruitment of L-type calcium channels. Moreover, by mapping these
      connections with single dendrite resolution we not only found that presynaptic
      dendrites preferentially target proximal regions, but such actions differ
      significantly across branches. Furthermore, local stimulation of interneuron
      dendrites did not result in global excitation, supporting the notion that these
      interneurons can operate as multiplexors, containing numerous independently
      operating input-output devices.

PMID- 22396425
TI  - Decrease in tonic inhibition contributes to increase in dentate semilunar granule
      cell excitability after brain injury.
AB  - Brain injury is an etiological factor for temporal lobe epilepsy and can lead to
      memory and cognitive impairments. A recently characterized excitatory neuronal
      class in the dentate molecular layer, semilunar granule cell (SGC), has been
      proposed to regulate dentate network activity patterns and working memory
      formation. Although SGCs, like granule cells, project to CA3, their typical
      sustained firing and associational axon collaterals suggest that they are
      functionally distinct from granule cells. We find that brain injury results in an
      enhancement of SGC excitability associated with an increase in input resistance 1
      week after trauma. In addition to prolonging miniature and spontaneous IPSC
      interevent intervals, brain injury significantly reduces the amplitude of tonic
      GABA currents in SGCs. The postinjury decrease in SGC tonic GABA currents is in
      direct contrast to the increase observed in granule cells after trauma. Although
      our observation that SGCs express Prox1 indicates a shared lineage with granule
      cells, data from control rats show that SGC tonic GABA currents are larger and
      sIPSC interevent intervals shorter than in granule cells, demonstrating inherent
      differences in inhibition between these cell types. GABA(A) receptor antagonists
      selectively augmented SGC input resistance in controls but not in head-injured
      rats. Moreover, post-traumatic differences in SGC firing were abolished in
      GABA(A) receptor blockers. Our data show that cell-type-specific post-traumatic
      decreases in tonic GABA currents boost SGC excitability after brain injury.
      Hyperexcitable SGCs could augment dentate throughput to CA3 and contribute
      substantively to the enhanced risk for epilepsy and memory dysfunction after
      traumatic brain injury.

PMID- 22396426
TI  - Kcna1 gene deletion lowers the behavioral sensitivity of mice to small changes in
      sound location and increases asynchronous brainstem auditory evoked potentials
      but does not affect hearing thresholds.
AB  - Sound localization along the azimuth depends on the sensitivity of binaural
      nuclei in the auditory brainstem to small differences in interaural level and
      timing occurring within a submillisecond epoch and on monaural pathways that
      transmit level and timing cues with high temporal fidelity to insure their
      coincident arrival at the binaural targets. The soma and axons of these brainstem
      neurons are heavily invested with ion channels containing the low-threshold
      potassium channel subunit Kv1.1, which previous in vitro and in vivo studies
      suggest are important for regulating their high input-output correspondence and
      temporal synchrony. We compared awake Kcna1-null mutant (Kcna1-/-) mice lacking
      Kv1.1 with Kcna1+/+ mice to determine whether Kv1.1 activity contributes to sound
      localization and examined anesthetized mice for absolute hearing thresholds for
      suprathreshold differences that may be revealed in the waveforms of auditory
      brainstem response potentials. The awake -/- mice tested with reflex modification
      audiometry had reduced sensitivity to an abrupt change in the location of a broad
      band noise compared to +/+ mice, while anesthetized -/- mice had normal absolute
      thresholds for tone pips but a high level of stimulus-evoked but asynchronous
      background activity. Evoked potential waveforms had progressively earlier peaks
      and troughs in -/- mice, but the amplitude excursions between adjacent features
      were identical in the two groups. Their greater excitability and asynchrony in
      suprathreshold evoked potentials coupled with their normal thresholds suggests
      that a disruption in central neural processing in -/- mice and not peripheral
      hearing loss is responsible for their poor sound localization.

PMID- 22396427
TI  - Nucleus accumbens response to incentive stimuli anticipation in children of
      alcoholics: relationships with precursive behavioral risk and lifetime alcohol
      use.
AB  - Children of alcoholics (COAs) are at elevated risk to develop alcohol and other
      substance use disorders. The neurobiological underpinnings of this heightened
      vulnerability are presently not well understood. This study investigated whether,
      in humans, COAs have different functioning of the mesolimbic reward circuitry
      beyond previous substance use confounds and examined potential group differences
      in neural response in relation to alcohol use and behavioral risk. We studied 20
      18- to 22-year-old COAs and 20 controls, developmentally well characterized for
      substance use and selected to match on sex, age, IQ, lifetime substance use and
      associated problems, and precursive (ages 12-14 years) externalizing behavioral
      risk. None met criteria for Diagnostic and Statistical Manual of Mental Disorders
      IV diagnosis. Neural responses to anticipation of reward and loss were assessed
      using functional magnetic resonance imaging during a monetary incentive delay
      task. Overall, COAs showed reduced ventral striatum activation during
      anticipation of monetary reward and loss compared with controls. However,
      additional analysis revealed that blunted nucleus accumbens (NAcc) response was
      only observed in COAs who have not demonstrated any problem drinking behavior. In
      addition, uniquely in COAs, NAcc activation was positively correlated with
      precursive externalizing risk, as well as current and lifetime alcohol
      consumption. These findings suggest a multilevel developmental process whereby
      lower precursive behavioral risk appears protective of later problem alcohol use
      in COAs, which is further associated with a blunted NAcc response to incentive
      anticipation, potentially reflecting a resilience mechanism. Moreover, the
      results suggest that a close association between motivational responses, alcohol
      consumption, and behavioral risk may underlie addiction vulnerability in COAs.

PMID- 22396429
TI  - Myrip couples the capture of secretory granules by the actin-rich cell cortex and
      their attachment to the plasma membrane.
AB  - Exocytosis of secretory granules (SGs) requires their delivery to the actin-rich
      cell cortex followed by their attachment to the plasma membrane (PM). How these
      reactions are executed and coordinated is still unclear. Myrip, which is also
      known as Slac-2c, binds to the SG-associated GTPase Rab27 and is thought to
      promote the delivery of SGs to the PM by recruiting the molecular motor myosin
      Va. Myrip also interacts with actin and the exocyst complex, suggesting that it
      may exert multiple roles in the secretory process. By combining total internal
      reflection fluorescence microscopy, single-particle tracking, a photoconversion
      based assay, and mathematical modeling, we show that, in human enterochromaffin
      cells, Myrip (1) inhibits a class of SG motion characterized by fast and directed
      movement, suggesting that it facilitates the dissociation of SGs from
      microtubules; (2) enhances their motion toward the PM and the probability of SG
      attachment to the PM; and (3) increases the characteristic time of immobilization
      at the PM, indicating that it is a component of the molecular machinery that
      tether SGs to the PM. Remarkably, while the first two effects of Myrip depend on
      its ability to recruit myosin Va on SGs, the third is myosin Va independent but
      relies on the C-terminal domain of Myrip. We conclude that Myrip couples the
      retention of SGs in the cell cortex, their transport to the PM, and their
      attachment to the PM, and thus promotes secretion. These three steps of the
      secretory process are thus intimately coordinated.

PMID- 22396428
TI  - Parasynaptic NMDA receptor signaling couples neuronal glutamate transporter
      function to AMPA receptor synaptic distribution and stability.
AB  - At synapses, two major processes occur concomitantly after the release of
      glutamate: activation of AMPA receptors (AMPARs) to conduct synaptic transmission
      and activation of excitatory amino acid transporters (EAATs) for transmitter
      removal. Although crosstalk between the receptors and EAATs is conceivable,
      whether and how the transporter activity affects AMPAR synaptic localization
      remain unknown. Using cultured hippocampal and cortical rat neurons, we show that
      inhibition of glutamate transporters leads to rapid reduction in AMPAR synaptic
      accumulation and total AMPAR abundance. EAAT inactivity also results in elevated
      internalization and reduced surface expression of AMPARs. The reduction in AMPAR
      amount is accompanied by receptor ubiquitination and can be blocked by
      suppression of proteasome activity, indicating the involvement of proteasome
      mediated receptor degradation. Consistent with glutamate spillover, effect of
      EAAT inhibition on AMPAR distribution and stability is dependent on the
      activation of parasynaptically localized NR2B-containing NMDA receptors (NMDARs).
      Moreover, we show that neuronal glutamate transporters, especially those
      localized at the postsynaptic sites, are responsible for the observed effect
      during EAAT suppression. These results indicate a role for neuron-specific
      glutamate transporters in AMPAR synaptic localization and stability.

PMID- 22396430
TI  - Effects of confounders and intermediates on the association of bacteraemia caused
      by extended-spectrum beta-lactamase-producing Enterobacteriaceae and patient
      outcome: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Bacteraemia caused by Enterobacteriaceae (EB)
      producing extended-spectrum beta-lactamase (ESBL+) has been associated with
      higher mortality compared with non-ESBL-producing (ESBL-) EB bacteraemia in
      observational studies. We conducted a systematic review and meta-analysis of
      these studies to assess how adjusting for confounding in multivariate analyses
      affects the pooled estimate, and whether multivariate analyses that include
      intermediates in the causal pathway of outcome (sepsis severity and inadequate
      empirical therapy) have lower estimates of attributable mortality. DATA SOURCES:
      PubMed search on 23 November 2010 followed by manually searching reference lists
      of included studies. STUDY ELIGIBILITY CRITERIA: Cohort studies published in
      English with separate mortality rates for ESBL+ and ESBL- EB bacteraemia.
      SYNTHESIS METHODS: Random-effects pooling of unadjusted and adjusted ORs followed
      by subgroup analyses to explore effects of adjustment procedures on adjusted ORs.
      RESULTS: The pooled OR for the unadjusted mortality associated with ESBL
      production was 2.35 (95% CI 1.90-2.91, I(2) = 42%, 32 studies). The pooled
      adjusted OR was 1.52 (95% CI 1.15-2.01, I(2) = 32%, 15 studies). Adjustment for
      more intermediates was associated with decreasing ORs. The pooled OR for the
      analyses adjusting for inadequate empirical therapy was 1.37 (95% CI 1.04-1.82).
      CONCLUSIONS: ESBL production in EB bacteraemia is associated with a higher
      mortality compared with bacteraemia with ESBL- EB, although the estimate of this
      association is affected by adjustment procedures. Adjustment for inadequate
      empirical therapy leads to a reduction in ORs, indicating that higher mortality
      is likely to be mediated through this phenomenon.

PMID- 22396431
TI  - Notice of retraction. Role of clofazimine in the treatment of multidrug-resistant
      tuberculosis: a retrospective observational cohort assessment.

PMID- 22396432
TI  - Co-location of the multiresistance gene cfr and the novel streptomycin resistance
      gene aadY on a small plasmid in a porcine Bacillus strain.

PMID- 22396433
TI  - Erythrocyte and plasma ribavirin concentrations in the assessment of early and
      sustained virological responses to pegylated interferon-alpha 2a and ribavirin in
      patients coinfected with hepatitis C virus and HIV.
AB  - OBJECTIVES: To determine the relationship between erythrocyte and plasma
      ribavirin concentrations in hepatitis C virus (HCV)/HIV-coinfected patients, and
      to correlate ribavirin exposure with early and sustained virological response
      (EVR and SVR) and haemoglobin level reductions. METHODS: Clinical and biological
      data from 68 HCV/HIV-coinfected patients were recorded at baseline, week 4 (W4),
      week 12 and at 24 weeks after completion of treatment. Plasma and erythrocyte
      ribavirin concentrations were determined 12 h after the final ribavirin dose
      (C(min)). RESULTS: Erythrocyte ribavirin concentrations were 100-fold higher than
      plasma concentrations, with a significant relationship between them (P < 0.05).
      In patients with HCV genotype 1 or 4, a plasma ribavirin C(min) threshold of 1.95
      mg/L at W4 tended to predict EVR [sensitivity 44%; specificity 87%; AUC 0.67 (95%
      CI 0.50-0.84)] and was predictive of SVR [sensitivity 58%; specificity 84%; AUC
      0.71 (95% CI 0.51-0.90)]. Among patients with these HCV genotypes, an erythrocyte
      ribavirin C(min) threshold of 146 mg/L at W4 was found to be the best value for
      discriminating between responders and non-responders for both EVR [sensitivity
      67%; specificity 75%; AUC 0.58 (95% CI 0.24-0.93)] and SVR [sensitivity 50%;
      specificity 80%; AUC 0.70 (95% CI 0.39-1.01)]. We also demonstrated a significant
      relationship between reduced haemoglobin levels and plasma ribavirin C(min) at W4
      (P = 0.05). CONCLUSIONS: Therapeutic drug monitoring may be useful for the
      management of anti-HCV treatment in HCV/HIV-coinfected patients.

PMID- 22396434
TI  - Resistant minority species are rarely observed in patients on darunavir/ritonavir
      monotherapy.
AB  - OBJECTIVES: To analyse the emergence of resistant viruses in patients failing
      darunavir monotherapy, including minority species, and to investigate the impact
      of baseline reverse transcriptase (RT), protease (PR) and gag resistance
      mutations on virological failure (VF) occurrence. METHODS: Nine of the 225 HIV-1
      infected patients enrolled in the MONOI trial (darunavir/ritonavir monotherapy or
      darunavir/ritonavir + two nucleoside reverse transcriptase inhibitors in a switch
      strategy) experienced VF, defined as two plasma HIV-1 viral loads >400 copies/mL
      at least 2 weeks apart. Among these nine patients with VF, five were in the
      darunavir/ritonavir monotherapy arm and four were in the darunavir/ritonavir
      triple therapy arm. Bulk sequences of the PR, RT and gag genes at baseline (on
      DNA) and at the time of VF (on RNA) were determined for all patients with two
      viral loads >50 copies/mL at least 2 weeks apart (n = 47). PR and gag gene clonal
      analysis was performed on plasma samples of the nine patients with VF. RESULTS:
      There was no association between mutations in RT, PR and gag genes in DNA and VF
      occurrence. None of the patients demonstrated selection of darunavir resistance
      mutations among the 47 patients with a viral load >50 copies/mL at least 2 weeks
      apart. The virus of one of the nine patients with VF presented minority variants
      with darunavir resistance mutations at positions 32, 47 and 50. Clonal analysis
      of the gag region for the nine patients with VF did not show any selection of
      minority variants. CONCLUSIONS: In patients with failure on darunavir/ritonavir
      monotherapy we did not find any selection of darunavir resistance mutations using
      standard genotype testing. However, the virus of one patient among nine failures
      presented minority variants plus darunavir resistance mutations.

PMID- 22396435
TI  - Do patients with OAB experience bladder sensations in the same way as healthy
      volunteers? A focus group investigation.
AB  - AIMS: To describe the terminology and pattern of bladder sensations experienced
      during non-invasive rapid bladder filling in a controlled setting in patients
      with OAB and to compare these results with a previous study conducted in healthy
      volunteers. METHODS: Three groups of patients with OAB, in total 10 patients,
      participated in three consecutive focus group sessions. Before each session a
      strict water loading protocol was given. During the first two sessions,
      participants described how they experienced their bladder sensations in daily
      life and during a non-invasive bladder filling with constant focus on their
      bladder. The third session focused on verifying the interpretation of the data
      gathered and describing the pattern of sensations. RESULTS: Patients describe
      their bladder sensations as a pressure or a tingling sensation and the pattern
      can be described by terms ranging from no sensation to an absolute need to void.
      The absolute need to void may develop suddenly or more slowly progressive. The
      mean development of bladder sensation is significantly different between patients
      and healthy volunteers as well as their average diuresis. CONCLUSIONS: Patients
      with OAB describe their bladder sensations as a pressure or a tingling sensation.
      There appear to be two types of urgency: a sudden absolute need to void and a
      slowly developing absolute need to void. Furthermore bladder sensation develops
      significantly different in volunteers than in OAB patients.

PMID- 22396436
TI  - Long-term functional plasticity in plant hydraulic architecture in response to
      supplemental moisture.
AB  - BACKGROUND AND AIMS: Plasticity in structural and functional traits related to
      water balance may determine plant performance and survival in ecosystems
      characterized by water limitation or high levels of rainfall variability,
      particularly in perennial herbaceous species with long generation cycles. This
      paper addresses whether and the extent to which several such seasonal to long
      term traits respond to changes in moisture availability. METHODS: Using a novel
      approach that integrates ecology, physiology and anatomy, a comparison was made
      of lifetime functional traits in the root xylem of a long-lived perennial herb
      (Potentilla diversifolia, Rosaceae) growing in dry habitats with those of nearby
      individuals growing where soil moisture had been supplemented for 14 years.
      Traditional parameters such as specific leaf area (SLA) and above-ground growth
      were also assessed. KEY RESULTS: Individuals from the site receiving supplemental
      moisture consistently showed significant responses in all considered traits
      related to water balance: SLA was greater by 24 %; roots developed 19 % less
      starch storing tissue, an indicator for drought-stress tolerance; and vessel size
      distributions shifted towards wider elements that collectively conducted water 54
      % more efficiently - but only during the years for which moisture was
      supplemented. In contrast, above-ground growth parameters showed insignificant or
      inconsistent responses. CONCLUSIONS: The phenotypic changes documented represent
      consistent, dynamic responses to increased moisture availability that should
      increase plant competitive ability. The functional plasticity of xylem anatomy
      quantified in this study constitutes a mechanistic basis for anticipating the
      differential success of plant species in response to climate variability and
      change, particularly where water limitation occurs.

PMID- 22396437
TI  - Quality of life of multiple sclerosis patients: translation and validation of the
      Spanish version of Qualiveen.
AB  - PURPOSE: Up until now there were no specific questionnaire translated into
      Spanish for evaluating urinary disorder specific health-related quality of life
      (HRQoL) associated with multiple sclerosis (MS). Qualiveen is recommended by the
      European Association of Urology guidelines as a tool for evaluating neurogenic
      lower urinary tract dysfunction. The objective was to translate the Qualiveen
      into Spanish, adapt it cross-culturally and validate it against the currently
      available tools. MATERIALS AND METHODS: A bidirectional translation of Qualiveen
      was undertaken by professional translators. One hundred two Spanish MS patients
      were sent the Qualiveen and the ICIQ-SF questionnaires twice within a month. The
      questionnaires were sent and received by mail and reviewed when the patients came
      for the scheduled visit. RESULTS: Eighty-one patients participated. The
      validation study showed that the Spanish version of Qualiveen has good internal
      consistency with Cronbach's coefficient superior to 0.80 for all the
      questionnaire's subdomains and also for the entire Qualiveen demonstrating high
      discriminative power. Also the test-retest analysis proved internal stability of
      the Qualiveen (kappa coefficient between 0.81 and 0.89). Finally, all the
      Qualiveen scores correlated with the ICIQ-SF final score. CONCLUSIONS: The
      Spanish version of Qualiveen functions similarly to the English language version
      retaining its discriminating power. It has shown it could be a valid instrument
      for discriminating between patients in a cross-sectional survey, as well as for
      measuring within subject changes over time thus evaluating the extent to which MS
      patients' HRQoL is impaired by urinary-related problems.

PMID- 22396438
TI  - Management of ovarian cancer: a 75-year-old woman who has completed treatment.
AB  - Ovarian cancer includes primary tumors of epithelial, sex cord-stromal, or germ
      cell origin as well as metastatic tumors that frequently originate in the
      gastrointestinal tract. Approximately 90% of ovarian cancer is epithelial in
      origin and constitutes a major therapeutic challenge because of its advanced
      stage of presentation in most patients. Epithelial ovarian cancer is the most
      lethal gynecologic malignancy and the fifth most common cause of female cancer
      death in the United States, with approximately 1 in 70 women developing this
      disease in their lifetime. Several important advances in surgical and medical
      management of this disease have led to prolongation of survival and improvement
      of quality of life of patients with ovarian cancer. Using the case of Ms W, we
      discuss the signs, symptoms, risk factors, and prognostic factors of epithelial
      ovarian cancer; review the evidence for surgical and postoperative medical
      management; and present the current recommendations for screening and follow-up.

PMID- 22396439
TI  - Who needs a Wada test? Present clinical indications for amobarbital procedures.
AB  - INTRODUCTION: The Wada test has been the gold standard for testing cerebral
      language localisation during presurgical investigation in the past decades.
      However, during the last few years a shift has occurred in epilepsy surgery
      programmes towards the use of non-invasive methods, predominantly functional MRI
      (fMRI). However, Wada tests are still performed, albeit in a considerably smaller
      number of patients at many epilepsy centres. METHODS: A retrospective monocentric
      analysis of remaining clinical indications for performing a Wada procedure was
      undertaken. The clinical data of patients who participated in Wada tests (42
      hemispheric and 8 superselective procedures) during recent years were
      retrospectively evaluated. RESULTS: Reasons for conducting a Wada test were (1) a
      patient's inability to perform the fMRI task due to agitation, mental
      disablement, or perceptual impairment, (2) validation of atypical, inconclusive
      or not clearly lateralised language activation shown with fMRI, (3) evaluation of
      propagation of ongoing interictal bilateral epileptiform EEG activity, (4) region
      selective testing of language and other cognitive functions, or (5) assessment of
      motor localisation. Patients who were not able to perform the fMRI task or in
      whom fMRI did not provide interpretable results were significantly younger
      (p<0.05). CONCLUSION: It is argued that fMRI is eligible to replace Wada tests in
      the majority of patients who are compliant with clearly lateralised language
      localisation, but in patients who are agitated or mentally impaired as well as in
      the case of the above-mentioned specific clinical indications and bilateral fMRI
      activations, Wada tests still provide additional information. Additionally, non
      invasive methods less sensitive to movement artefacts are discussed as possible
      alternatives for these patients.

PMID- 22396440
TI  - Construction and pilot assessment of the Upper Limb Assessment in Daily Living
      Scale.
AB  - OBJECTIVE: The upper limb function of hemiplegic patients is currently evaluated
      using scales that assess physical capacity or daily activities under test
      conditions. The present scale, the Upper Limb Assessment in Daily Living (ULADL)
      Scale, was developed to explore the subjective and objective functional
      capacities of such patients in a proximal to distal sequence. METHODS: A group of
      experts constructed a scale addressing 17 upper limb functions (five active
      passive and 12 active) which could be explored by a questionnaire (Q) and a test
      (T). Reproducibility, internal consistency, concurrent validity (Rivermead Motor
      Assessment (RMA)) and learning effect were estimated in a multicentre study.
      RESULTS: 49 stroke patients were each rated three times within 7 days by a total
      of 21 physicians, yielding a total of 142 ratings. The ULADL took 16+/-8 min to
      complete compared with 9+/-5 min for the RMA. Cronbach's alpha coefficient was
      0.95 for Q and 0.97 for the practical tests (T). The global Q and T scores, and
      in particular the global Q score, were slightly higher at the second rating. The
      intra-rater intraclass correlation coefficient (ICC) was 0.65 (95% CI (0.44 to
      0.79)) for Q and 0.97 (0.95 to 0.98) for T, and the inter-rater ICC was 0.95 for
      both Q and T. The Bland and Altman method showed good intra- and inter-rater
      reliability with no systematic trend. Correlation coefficients for ULADL versus
      RMA were >0.80 for both Q and T. CONCLUSIONS: The ULADL Scale has good
      psychometric properties and can explore patients with different degrees of upper
      limb impairment.

PMID- 22396441
TI  - Uniform demyelination and more severe axonal loss distinguish POEMS syndrome from
      CIDP.
AB  - OBJECTIVE: POEMS syndrome (the acronym reflects the common features:
      Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and Skin
      changes) is a paraneoplastic disorder with a 'demyelinating' peripheral
      neuropathy that is often mistaken for chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP). The nerve conduction study (NCS) and
      electromyography (EMG) attributes that might differentiate POEMS from CIDP and
      lead to earlier therapeutic intervention were explored. METHODS: NCS/EMG of POEMS
      patients identified through retrospective review from 1960 to 2007 were compared
      with matched CIDP controls. RESULTS: 138 POEMS patients and 69 matched CIDP
      controls were compared. POEMS patients demonstrated length dependent reduction in
      compound muscle action potentials, low conduction velocities, prolonged distal
      latencies and prolonged F wave latencies. Compared with CIDP controls, POEMS
      patients demonstrated: (1) greater reduction of motor amplitudes, (2) greater
      slowing of motor and sensory conduction velocities, (3) less prolonged motor
      distal latencies, (4) less frequent temporal dispersion and conduction block, (5)
      no sural sparing, (6) greater number of fibrillation potentials in a length
      dependent pattern and (7) higher terminal latency indices (TLI). TLI >=0.38 in
      the median nerve demonstrated a sensitivity of 70% and specificity of 77% in
      discriminating POEMS from CIDP. CONCLUSIONS: NCS/EMG of POEMS syndrome suggests
      both axonal loss and demyelination. Compared with CIDP, there is greater axonal
      loss (reduction of motor amplitudes and increased fibrillation potentials),
      greater slowing of the intermediate nerve segments, less common temporal
      dispersion and conduction block, and absent sural sparing. These findings imply
      that the pathology of POEMS syndrome is diffusely distributed (uniform
      demyelination) along the nerve where the pathology of CIDP is probably
      predominantly proximal and distal. Median motor TLI may be useful in clinically
      distinguishing these disorders.

PMID- 22396442
TI  - Key concepts in glioblastoma therapy.
AB  - Glioblastoma is the most common form of primary brain cancer and remains one of
      the most aggressive forms of human cancer. Current standard of care involves
      maximal surgical resection followed by concurrent therapy with radiation and the
      DNA alkylating agent temozolomide. Despite this aggressive regimen, the median
      survival remains approximately 14 months. Meaningful strategies for therapeutic
      intervention are desperately needed. Development of such strategies will require
      an understanding of the therapeutic concepts that have evolved over the past
      three decades. This article reviews the key principles that drive the formulation
      of therapeutic strategies in glioblastoma. Specifically, the concepts of tumour
      heterogeneity, oncogene addiction, non-oncogene addiction, tumour initiating
      cells, tumour microenvironment, non-coding sequences and DNA damage response will
      be reviewed.

PMID- 22396443
TI  - Cognitive changes in multiethnic Asian breast cancer patients: a focus group
      study.
AB  - BACKGROUND: This study aims to gather descriptions from multiethnic Asian breast
      cancer patients on their experiences and impact of chemotherapy-associated
      cognitive changes on their daily lives and their coping strategies. PATIENTS AND
      METHODS: Forty-three chemotherapy-receiving breast cancer patients participated
      in eight English or Chinese structured focus group discussions, conducted by
      trained psychosocial oncologists and medical social workers. RESULTS:
      Participants were unfamiliar and averse to both English and Chinese-translated
      equivalent of the term 'chemobrain'. Participants viewed this phenomenon
      holistically as a by-product of the physical (fatigue and aging) and psychosocial
      (anxiety and mood changes) adverse effects associated with chemotherapy. Most
      participants encountered memory loss, difficulty in decision making and speech
      problems after receiving chemotherapy. Married participants expressed frustration
      as cognitive deterioration limited their conservative roles as homemakers.
      Despite knowing the potential neurocognitive effects, participants valued the
      benefits of chemotherapy. Identified coping strategies included playing mahjong
      for mind stimulation and management of psychosocial factors, such as practicing
      qi gong, to regulate their moods and to take complementary alternative medicines
      to reduce the severity of their fatigue. CONCLUSIONS: The phenomenon 'chemobrain'
      is unfamiliar to most Asian cancer patients yet it has significantly impacted
      their daily lives. Our results suggested that a culturally relevant approach
      should be adopted to evaluate and manage cognitive changes in these patients.

PMID- 22396445
TI  - Changes in survival by ethnicity of patients with cancer between 1992-1996 and
      2002-2006: is the discrepancy decreasing?
AB  - BACKGROUND: Patients of minority race/ethnicity have lower survival after
      diagnosis with most types of cancer. Little data are available concerning changes
      in disparity over time. Here, we examine changes in survival by race/ethnicity of
      patients with common cancers in two recent time periods. PATIENTS AND METHODS: We
      used modeled period analysis to determine relative survival (RS) for non-Hispanic
      white (nHw), African-American (AA), and Hispanic patients in the Surveillance,
      Epidemiology, and End Results database diagnosed with common solid and
      hematological malignancies. RESULTS: Five-year RS improved overall and for nHw
      for each tumor examined, ranging from + 2% points (pancreatic cancer) to + 16.4%
      points [non-Hodgkin's lymphoma, (NHL)]. Greater improvement was observed for AA
      and Hispanics than nHw in breast and prostate cancer and NHL. Less improvement
      was observed for AA and Hispanics than for nHw for lung and pancreatic cancer. No
      statistically significant improvement was observed for AA and Hispanics with
      myeloma or acute leukemia. Survival disparities ranging from 0.5% points
      (myeloma) to 13.1% points (breast) between nHw and AA remained. CONCLUSIONS:
      Progress has been made in decreasing disparities in survival between nHw and
      minorities in breast cancer, prostate cancer, and NHL. Little progress has been
      made in reducing disparities for the other studied cancers.

PMID- 22396444
TI  - The effect of guideline-consistent antiemetic therapy on chemotherapy-induced
      nausea and vomiting (CINV): the Pan European Emesis Registry (PEER).
AB  - BACKGROUND: While guidelines for preventing chemotherapy-induced nausea and
      vomiting (CINV) are widely available, clinical uptake of guidelines remains low.
      Our objective was to evaluate the effect of guideline-consistent CINV prophylaxis
      (GCCP) on patient outcomes. PATIENTS AND METHODS: This prospective, observational
      multicenter study enrolled chemotherapy-naive adults initiating single-day highly
      or moderately emetogenic chemotherapy (HEC or MEC) for cancer. Patients completed
      6-day daily diaries beginning with cycle 1 for up to three chemotherapy cycles.
      The primary study end point, complete response (no emesis and no use of rescue
      therapy) during 120 h after cycle 1 chemotherapy, was compared between GCCP and
      guideline-inconsistent CINV prophylaxis (GICP) cohorts using multivariate
      logistic regression, adjusting for potential confounding factors. RESULTS: In
      cycle 1 (N=991), use of GCCP was 55% and 46% during acute and delayed phases,
      respectively, and 29 % for the overall study period (acute plus delayed phases).
      Complete response was recorded by 172/287 (59.9%) and 357/704 (50.7%) patients in
      GCCP and GICP cohorts, respectively (P=0.008). The adjusted odds ratio for
      complete response was 1.43 (95% confidence interval 1.04-1.97; P=0.027) for
      patients receiving GCCP versus GICP. CONCLUSION: GCCP reduces the incidence of
      CINV after single-day HEC and MEC.

PMID- 22396446
TI  - Prognostic impact of meningeal dissemination in primary CNS lymphoma (PCNSL):
      experience from the G-PCNSL-SG1 trial.
AB  - BACKGROUND: We evaluated the frequency and prognostic impact of meningeal
      dissemination (MD) in immunocompetent adult patients with primary central nervous
      system lymphoma treated in a randomized phase III trial. PATIENTS AND METHODS: MD
      was evaluated at study entry and defined by lymphoma proof in the meningeal
      compartment detected by at least one of the following methods: cerebrospinal
      fluid (CSF) cytomorphology, detection of clonal B cells by IgH PCR in CSF or
      contrast enhancement of the leptomeninges on magnetic resonance imaging (MRI).
      RESULTS: Data on MD were available in 415 patients, of those, MD was detected in
      65 (15.7%): in 44/361 (12.2%) by CSF cytomorphology, in 16/152 (10.5%) by PCR and
      in 17/415 (4.1%) by MRI. Major patients' characteristics and therapy did not
      significantly differ between patients with MD (MD+) versus those without MD (MD
      ). There was a significant correlation of MD with CSF pleocytosis (>5/MUl; P <
      0.0001), but no correlation with CSF protein elevation (>45 mg/dl). Median
      progression-free survival was 6.7 months [95% confidence interval (CI) 0-14.5] in
      MD+ and 8.3 months (5.7-10.8) in MD- patients (P = 0.95); median overall survival
      was 21.5 months (95% CI 16.8-26.1) and 24.9 months (17.5-32.3), respectively (P =
      0.98). CONCLUSION: MD was detected infrequently and had no impact on outcome in
      this trial.

PMID- 22396448
TI  - The lipid peroxidation by-product 4-hydroxy-2-nonenal (4-HNE) induces insulin
      resistance in skeletal muscle through both carbonyl and oxidative stress.
AB  - Numerous oxidants are produced as by-products of aerobic cell metabolism, and
      there is growing evidence that they play key roles in the pathogenesis of insulin
      resistance. Under conditions of oxidative stress, lipid peroxidation of omega6
      polyunsaturated fatty acids leads to the production of 4-hydroxy-2-nonenal (4
      HNE). Several lines of evidence suggest that 4-HNE could be involved in the
      pathophysiology of metabolic diseases; therefore, in this study we assessed the
      direct effects of 4-HNE on skeletal muscle insulin sensitivity. Gastrocnemius
      muscle and L6 muscle cells were treated with 4-HNE. Insulin signaling was
      measured by Western blotting and glucose uptake using 2-deoxy-d-[3H]glucose.
      Carbonyl stress, glutathione content, and oxidative stress were assessed as
      potential mechanisms leading to insulin resistance. Protection of cells was
      induced by pretreatment with 3H-1,2-dithiole-3-thione, N-acetyl-cysteine,
      aminoguanidine, or S-adenosyl-methionine. 4-HNE induced a time- and dose
      dependent decrease in insulin signaling and insulin-induced glucose uptake in
      muscle. It induced a state of carbonyl stress through adduction of proteins as
      well as a depletion in reduced glutathione and production of radical oxygen
      species. A pharmacological increase in glutathione pools was achieved by 3H-1,2
      dithiole-3-thione and protected the cells against all deleterious effects of 4
      HNE; furthermore, N-acetylcysteine, aminoguanidine, and S-adenosylmethionine
      prevented 4-HNE noxious effects. 4-HNE can impair insulin action in muscle cells
      through oxidative stress and oxidative damage to proteins, eventually leading to
      insulin resistance. These deleterious effects can be prevented by pretreatment
      with antioxidants, scavengers, or an increase in intracellular glutathione pools.
      Use of such molecules could represent a novel strategy to combat insulin
      resistance and other oxidative stress-associated pathologies.

PMID- 22396447
TI  - Cetuximab rechallenge in metastatic colorectal cancer patients: how to come away
      from acquired resistance?
AB  - BACKGROUND: Scientific data provide the evidence that secondary K-RAS mutations
      do not occur during anti-epidermal growth factor receptor therapy in colorectal
      cancer patients. This multicenter phase II prospective study aims to investigate
      the activity of a retreatment with a cetuximab-based therapy. PATIENTS AND
      METHODS: We enrolled 39 irinotecan-refractory patients who had a clinical benefit
      after a line of cetuximab- plus irinotecan-based therapy and then a progression
      of disease for which underwent a new line chemotherapy and finally, after a clear
      new progression of disease, were retreated with the same cetuximab- plus
      irinotecan-based therapy. RESULTS: Median number of therapeutic lines before
      accrual was 4. Median interval time between last cycle of first cetuximab-based
      therapy and first cycle of the retreatment was 6 months. Overall response rate
      was 53.8% with 19 partial responses (48.7%) and 2 complete responses (5.1%).
      Disease stabilization was obtained in 35.9% of patients and progression in four
      patients (10.2%). Median progression-free survival was 6.6 months. The
      correlation between skin toxicity during first cetuximab therapy and during
      cetuximab rechallenge was significant (P = 0.01). CONCLUSION: Rechallenge with
      the same cetuximab-based therapy may achieve a new important clinical benefit
      further delaying the progression of disease and improving the therapeutic
      options.

PMID- 22396449
TI  - Recurrent hypoglycemia is associated with loss of activation in rat brain
      cingulate cortex.
AB  - A subset of people with diabetes fail to mount defensive counterregulatory
      responses (CRR) to hypoglycemia. Although the mechanisms by which this occurs
      remain unclear, recurrent exposure to hypoglycemia may be an important
      etiological factor. We hypothesized that loss of CRR to recurrent exposure to
      hypoglycemia represents a type of stress desensitization, in which limbic brain
      circuitry involved in modulating stress responses might be implicated. Here, we
      compared activation of limbic brain regions associated with stress
      desensitization during acute hypoglycemia (AH) and recurrent hypoglycemia (RH).
      Healthy Sprague Dawley rats were exposed to either acute or recurrent 3-d
      hypoglycemia. We also examined whether changes in neuronal activation were caused
      directly by the CRR itself by infusing epinephrine, glucagon, and corticosterone
      without hypoglycemia. AH increased neuronal activity as quantified by c-fos
      immunoreactivity (FOS-IR) in the cingulate cortex and associated ectorhinal and
      perirhinal cortices but not in an adjacent control area (primary somatosensory
      cortex). FOS-IR was not observed after hormone infusion, suggesting that AH
      associated activation was caused by hypoglycemia rather than by CRR. Importantly,
      AH FOS-IR activation was significantly blunted in rats exposed to RH. In
      conclusion, analogous with other models of stress habituation, activation in the
      cingulate cortex and associated brain areas is lost with exposure to RH. Our data
      support the hypothesis that limbic brain areas may be associated with the loss of
      CRR to RH in diabetes.

PMID- 22396450
TI  - Minireview: animal models and mechanisms of ovarian cancer development.
AB  - Ovarian cancer in women is a complex and deadly disease, where the molecular
      events that initiate and control tumor formation remain poorly defined.
      Therefore, mouse models provide one approach for determining the mechanisms by
      which specific oncogenic factors cause ovarian surface epithelial cell and
      granulosa cell transformation. This minireview summarizes the phenotypes of
      current mouse models that have been generated and some of the underlying
      mechanisms they have provided.

PMID- 22396451
TI  - Wild-type tumor repressor protein 53 (Trp53) promotes ovarian cancer cell
      survival.
AB  - Loss of Pten in the Kras(G12D);Amhr2-Cre mutant mice leads to the transformation
      of ovarian surface epithelial (OSE) cells and rapid development of low-grade,
      invasive serous adenocarcinomas. Tumors occur with 100% penetrance and express
      elevated levels of wild-type tumor repressor protein 53 (TRP53). To test the
      functions of TRP53 in the Pten;Kras (Trp53+) mice, we disrupted the Trp53 gene
      yielding Pten;Kras(Trp53-) mice. By comparing morphology and gene expression
      profiles in the Trp53+ and Trp53- OSE cells from these mice, we document that
      wild-type TRP53 acts as a major promoter of OSE cell survival and
      differentiation: cells lacking Trp53 are transformed yet are less adherent,
      migratory, and invasive and exhibit a gene expression profile more like normal
      OSE cells. These results provide a new paradigm: wild-type TRP53 does not
      preferentially induce apoptotic or senescent related genes in the
      Pten;Kras(Trp53+) cancer cells but rather increases genes regulating DNA repair,
      cell cycle progression, and proliferation and decreases putative tumor suppressor
      genes. However, if TRP53 activity is forced higher by exposure to nutlin-3a (a
      mouse double minute-2 antagonist), TRP53 suppresses DNA repair genes and induces
      the expression of genes that control cell cycle arrest and apoptosis. Thus, in
      the Pten;Kras(Trp53+) mutant mouse OSE cells and likely in human TP53+ low-grade
      ovarian cancer cells, wild-type TRP53 controls global molecular changes that are
      dependent on its activation status. These results suggest that activation of TP53
      may provide a promising new therapy for managing low-grade ovarian cancer and
      other cancers in humans in which wild-type TP53 is expressed.

PMID- 22396453
TI  - Early parenteral nutrition evokes a phenotype of autophagy deficiency in liver
      and skeletal muscle of critically ill rabbits.
AB  - Muscular and hepatic abnormalities observed in artificially fed critically ill
      patients strikingly resemble the phenotype of autophagy-deficient mice. Autophagy
      is the only pathway to clear damaged organelles and large ubiquitinated proteins
      and aggregates. Fasting is its strongest physiological trigger. Severity of
      autophagy deficiency in critically ill patients correlated with the amount of
      infused amino acids. We hypothesized that impaired autophagy in critically ill
      patients could partly be evoked by early provision of parenteral nutrition
      enriched with amino acids in clinically used amounts. In a randomized laboratory
      investigation, we compared the effect of isocaloric moderate-dose iv feeding with
      fasting during illness on the previously studied markers of autophagy deficiency
      in skeletal muscle and liver. Critically ill rabbits were allocated to fasting or
      to iv nutrition (220 kcal/d, 921 kJ/d) supplemented with 50 kcal/d (209 kJ/d) of
      either glucose, amino acids, or lipids, while maintaining normoglycemia, and were
      compared with healthy controls. Fasted critically ill rabbits revealed weight
      loss and activation of autophagy. Feeding abolished these responses, with most
      impact of amino acid-enriched nutrition. Accumulation of p62 and ubiquitinated
      proteins in muscle and liver, indicative of insufficient autophagy, occurred with
      parenteral feeding enriched with amino acids and lipids. In liver, this was
      accompanied by fewer autophagosomes, fewer intact mitochondria, suppressed
      respiratory chain activity, and an increase in markers of liver damage. In
      muscle, early parenteral nutrition enriched with amino acids or lipids aggravated
      vacuolization of myofibers. In conclusion, early parenteral nutrition during
      critical illness evoked a phenotype of autophagy deficiency in liver and skeletal
      muscle.

PMID- 22396454
TI  - Nodal signaling regulates the entry into meiosis in fetal germ cells.
AB  - The mechanisms regulating the entry into meiosis in mammalian germ cells remain
      incompletely understood. We investigated the involvement of the TGF-beta family
      members in fetal germ cell meiosis initiation. Nodal, a member of the TGF-beta
      family, and its target genes are precociously expressed in embryonic gonads and
      show sexual dimorphism in favor of the developing testis. Nodal receptor genes,
      Acvr2a and Acvr2b, Alk4, and Tdgf1/Cripto, were identified in male germ cells.
      Nodal itself, Tdgf1, and Lefty1 and Lefty2 are targets of Nodal signaling and
      were all found specifically expressed in male germ cells. To elucidate the role
      of this signaling pathway, activin-like kinases that mediate TGF
      beta/Nodal/activin signaling were inhibited in 11.5 d postconception testis in
      organotypic culture. Activin-like kinases inhibition disrupted normal male germ
      cell development and induced germ cell entry into meiosis such as that observed
      in female germ cells at the equivalent stage. Interestingly Stra8, the gatekeeper
      of the mitotic/meiotic switch, was induced independently of any change of either
      Cyp26b1 or Fgf9 expression, the two genes currently identified as testicular
      meiotic inhibitors. On the other hand, recombinant Nodal significantly dampened
      Stra8 expression and germ cell meiosis in cultured 11.5 d postconception ovaries.
      Our results allowed us to propose for the first time an autocrine role of Nodal
      during the development of germ cells and indicate that members of the TGB-beta
      family may reinforce the male fate and prevent meiosis in embryonic germ cells.

PMID- 22396452
TI  - Ionotropic glutamate receptors in hypothalamic paraventricular and supraoptic
      nuclei mediate vasopressin and oxytocin release in unanesthetized rats.
AB  - We report changes in plasma arginine vasopressin (AVP) and oxytocin (OT)
      concentrations evoked by the microinjection of l-glutamate (l-glu) into the
      hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) of
      unanesthetized rats, as well as which local mechanisms are involved in their
      mediation. l-Glu microinjection (10 nmol/100 nl) into the SON increased the
      circulating levels of both AVP and OT. The AVP increases were blocked by local
      pretreatment with the selective non-N-methyl-d-aspartate (NMDA) receptor
      antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide
      (NBQX) (2 nmol/100 nl), but it was not affected by pretreatment with the NMDA
      receptor antagonist LY235959 (2 nmol/100 nl). The OT response to l-glu
      microinjection into the SON was blocked by local pretreatment with either NBQX or
      LY235959. Furthermore, the administration of either the non-NMDA receptor agonist
      (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide
      (AMPA) (5 nmol/100 nl) or NMDA receptor agonist NMDA (5 nmol/100 nl) into the SON
      had no effect on OT baseline plasma levels, but when both agonists were
      microinjected together these levels were increased. l-Glu microinjection into the
      PVN did not change circulating levels of either AVP or OT. However, after local
      pretreatment with LY235959, the l-glu microinjection increased plasma levels of
      the hormones. The l-glu microinjection into the PVN after the local treatment
      with NBQX did not affect the circulating AVP and OT levels. Therefore, results
      suggest the AVP release from the SON is mediated by activation of non-NMDA
      glutamate receptors, whereas the OT release from this nucleus is mediated by an
      interaction of NMDA and non-NMDA receptors. The present study also suggests an
      inhibitory role for NMDA receptors in the PVN on the release of AVP and OT.

PMID- 22396455
TI  - Estrogen stimulates leptin receptor expression in ATDC5 cells via the estrogen
      receptor and extracellular signal-regulated kinase pathways.
AB  - Regulation of the physiological processes of endochondral bone formation during
      long bone growth is controlled by various factors including the hormones estrogen
      and leptin. The effects of estrogen are mediated not only through the direct
      activity of estrogen receptors (ERs) but also through cross talk with other
      signaling systems implicated in chondrogenesis. The receptors of both estrogen
      and leptin (OBR (LEPR)) are detectable in growth plate chondrocytes of all zones.
      In this study, the expression of mRNA and protein of OBR in chondrogenic ATDC5
      cells and the effect of 17beta-estradiol (E(2)) stimulation were assessed using
      quantitative PCR and western blotting. We have found that the mRNA of Obr was
      dynamically expressed during the differentiation of ATDC5 cells over 21 days.
      Application of E(2) (10(-7) M) at day 14 for 48 h significantly upregulated OBR
      mRNA and protein levels (P<0.05). The upregulation of Obr mRNA by E(2) was shown
      to take place in a concentration-dependent manner, with a concentration of 10(-7)
      M E(2) having the greatest effect. Furthermore, we have confirmed that E(2)
      affected the phosphorylation of ERK1/2 (MAPK1/MAPK3) in a time-dependent manner
      where a maximal fourfold change was observed at 10 min following application of
      E(2). Finally, pretreatment of the cells with either U0126 (ERK1/2 inhibitor) or
      ICI 182 780 (ER antagonist) blocked the upregulation of OBR by E(2) and prevented
      the E(2)-induced phosphorylation of ERK. These data demonstrate, for the first
      time, the existence of cross talk between estrogen and OBR in the regulation of
      bone growth whereby estrogen regulates the expression of Obr in growth plate
      chondrocytes via ERs and the activation of ERK1/2 signaling pathways.

PMID- 22396456
TI  - Purinergic signalling in the pancreas in health and disease.
AB  - Pancreatic cells contain specialised stores for ATP. Purinergic receptors (P2 and
      P1) and ecto-nucleotidases are expressed in both endocrine and exocrine calls, as
      well as in stromal cells. The pancreas, especially the endocrine cells, were an
      early target for the actions of ATP. After the historical perspective of
      purinergic signalling in the pancreas, the focus of this review will be the
      physiological functions of purinergic signalling in the regulation of both
      endocrine and exocrine pancreas. Next, we will consider possible interaction
      between purinergic signalling and other regulatory systems and their relation to
      nutrient homeostasis and cell survival. The pancreas is an organ exhibiting
      several serious diseases - cystic fibrosis, pancreatitis, pancreatic cancer and
      diabetes - and some are associated with changes in life-style and are increasing
      in incidence. There is upcoming evidence for the role of purinergic signalling in
      the pathophysiology of the pancreas, and the new challenge is to understand how
      it is integrated with other pathological processes.

PMID- 22396457
TI  - Introductory paragraph - Volume 26, Issue 4.

PMID- 22396458
TI  - Dysarthria following stroke: the patient's perspective on management and
      rehabilitation.

PMID- 22396459
TI  - Cardiac resynchronization therapy in patients with permanent atrial fibrillation.
      Is it mandatory to ablate the atrioventricular junction to obtain a good
      response?
AB  - AIM: Current guidelines recommend atrioventricular junction (AVJ) ablation in
      patients with atrial fibrillation (AF) treated with cardiac resynchronization
      therapy (CRT). Our study compared the CRT response of patients in sinus rhythm
      (SR) vs. AF. METHODS AND RESULTS: In this observational, prospective, multicentre
      study, patients were grouped by intrinsic rhythm. For the first 2 months, the
      negative chronotropic drug was optimized in the AF group. If ventricular pacing
      was <=85%, AVJ ablation was recommended. Responders were defined as patients who
      survived without requiring heart transplant and had a >= 10% reduction in left
      ventricular end-systolic volume (LVESV) at 12 months after implantation. Of 202
      patients included, 156 (77%) were in SR and 46 (23%) had AF. After drug
      optimization, only 13/46 (28%) of the AF patients required AVJ ablation (AF +
      AVJ). The percentage of responders was 83/156 (53%) for SR vs. 22/46 (48%) AF (P
      = 0.4). Among AF patients the response was 16/33 (48%) for AF with non-AVJ
      ablation vs. 6/13 (46%) AF + AVJ, P = 0.56. The LVESV decreased in all three
      groups: -30 +/- 39 mL, -24 +/- 43 mL, and -22 +/- 36 mL, respectively (P = 0.75).
      Mortality was higher in patients with AF compared with SR: 10/46 (21%) vs. 9/156
      (5.7%), log rank 10.6, P <0.05. CONCLUSION: Although only 28% of the patients in
      AF had the AVJ ablated, there were no differences in the percentage of response
      and echo improvement between patients in SR and AF. However, mortality was higher
      in patients with AF compared with patients in SR.

PMID- 22396460
TI  - A dynamic framework for quantifying the genetic architecture of phenotypic
      plasticity.
AB  - Despite its central role in the adaptation and microevolution of traits, the
      genetic architecture of phenotypic plasticity, i.e. multiple phenotypes produced
      by a single genotype in changing environments, remains elusive. We know little
      about the genes that underlie the plastic response of traits to the environment,
      their number, chromosomal locations and genetic interactions as well as
      environment impact on their effects. Here we review key statistical approaches
      for analyzing the genetic variation of phenotypic plasticity due to genotype
      environment interactions and describe the implementation of a dynamic model to
      map specific quantitative trait loci (QTLs) that affect the gradient expression
      of a quantitative trait across a range of environments. This dynamic model is
      distinct by incorporating mathematical aspects of phenotypic plasticity into a
      QTL mapping framework, thereby better unraveling the quantitative attribute of
      trait response to the environment. By testing the curve parameters that specify
      environment-dependent trajectories of the trait, the model allows a series of
      fundamental hypotheses to be tested in a quantitative way about the interplay
      between gene action/interaction and environmental sensitivity. The model can also
      make the dynamic prediction of genetic control over phenotypic plasticity within
      the context of changing environments. We demonstrate the usefulness of the model
      by reanalyzing a QTL data set for rice, gleaning new insights into the genetic
      basis for phenotypic plasticity in plant height growth.

PMID- 22396461
TI  - Adjusting confounders in ranking biomarkers: a model-based ROC approach.
AB  - High-throughput studies have been extensively conducted in the research of
      complex human diseases. As a representative example, consider gene-expression
      studies where thousands of genes are profiled at the same time. An important
      objective of such studies is to rank the diagnostic accuracy of biomarkers (e.g.
      gene expressions) for predicting outcome variables while properly adjusting for
      confounding effects from low-dimensional clinical risk factors and environmental
      exposures. Existing approaches are often fully based on parametric or semi
      parametric models and target evaluating estimation significance as opposed to
      diagnostic accuracy. Receiver operating characteristic (ROC) approaches can be
      employed to tackle this problem. However, existing ROC ranking methods focus on
      biomarkers only and ignore effects of confounders. In this article, we propose a
      model-based approach which ranks the diagnostic accuracy of biomarkers using ROC
      measures with a proper adjustment of confounding effects. To this end, three
      different methods for constructing the underlying regression models are
      investigated. Simulation study shows that the proposed methods can accurately
      identify biomarkers with additional diagnostic power beyond confounders. Analysis
      of two cancer gene-expression studies demonstrates that adjusting for confounders
      can lead to substantially different rankings of genes.

PMID- 22396462
TI  - Blindness to a simultaneous change of all elements in a scene, unless there is a
      change in summary statistics.
AB  - Sudden change of every object in a display is typically conspicuous. We find
      however that in the presence of a secondary task, with a display of moving dots,
      it can be difficult to detect a sudden change in color of all the dots. A field
      of 200 dots, half red and half green, half moving rightward and half moving
      leftward, gave the appearance of two surfaces. When all 200 dots simultaneously
      switched color between red and green, performance in detecting the switch was
      very poor. A key display characteristic was that the color proportions on each
      surface (summary statistics) were not affected by the color switch. When the
      color switch is accompanied by a change in these summary statistics, people
      perform well in detecting the switch, suggesting that the secondary task does not
      disrupt the availability of this statistical information. These findings suggest
      that when the change is missed, the old and new colors were represented, but the
      color-location pattern (binding of colors to locations) was not represented or
      not compared. Even after extended viewing, changes to the individual color
      location pattern are not available, suggesting that the feeling of seeing these
      details is misleading.

PMID- 22396463
TI  - Different types of feedback change decision criterion and sensitivity differently
      in perceptual learning.
AB  - In (perceptual) learning, performance improves with practice either by changes in
      sensitivity or decision criterion. Often, changes in sensitivity are regarded as
      the appropriate measure of learning while changes in criterion are considered
      unavoidable nuisances. Very little is known about the distinguishing
      characteristics of both learning types. Here, we show first that block feedback,
      which affects sensitivity, does not affect criterion. Second, contrary to changes
      in sensitivity, changes in decision criterion are limited to the training session
      and do not transfer overnight. Finally, training with biased trial-wise feedback
      induces a sensitivity change such that a left offset Vernier may be perceived as
      a right offset Vernier.

PMID- 22396464
TI  - The role of discrepant retinal motion during walking in the realignment of
      egocentric space.
AB  - Visually guided action relies on accurate perception of egocentric direction.
      Unfortunately, perceived direction easily becomes misaligned. How is this problem
      overcome? One theory (R. Held & S. J. Freedman, 1963) is that during self
      movement the observer uses the relationship between anticipated and experienced
      sensory feedback as a source of information to maintain alignment. However, data
      supporting this theory is equivocal, and recent evidence appears contradictory.
      We reexamined the issue. We injected an error into perceived visual direction and
      then assessed realignment after a period of walking toward a target. We
      manipulated the sensory information available (presence of retinal motion,
      Experiment 1; presence of peripheral motion, Experiment 2) and found that as the
      amount of retinal motion was reduced (Experiments 1 and 2), realignment of
      perceived visual direction decreased. When we then (Experiment 3) removed the
      discrepancy between anticipated and experienced retinal motion, no realignment
      was observed. Our results provide evidence that a discrepancy between anticipated
      and experienced sensory feedback is an important source of information for the
      alignment of egocentric space, with retinal motion having a particular role in
      driving a realignment of perceived visual direction.

PMID- 22396465
TI  - Which image is in awareness during binocular rivalry? Reading perceptual status
      from eye movements.
AB  - Binocular rivalry is a useful psychophysical tool to investigate neural
      correlates of visual consciousness because the alternation between awareness of
      the left and right eye images occurs without any accompanying change in visual
      input. The conventional experiments on binocular rivalry require participants to
      voluntarily report their perceptual state. Obtaining reliable reports from non
      human primates about their subjective visual experience, however, requires long
      term training, which has made electrophysiological experiments on binocular
      rivalry quite difficult. Here, we developed a new binocular rivalry stimulus that
      consists of two different object images that are phase-shifted to move in
      opposite directions from each other: One eye receives leftward motion while the
      other eye receives rightward motion, although both eyes' images are perceived to
      remain at the same position. Experiments on adult human participants showed that
      eye movements (optokinetic nystagmus, OKN) are involuntarily evoked during the
      observation of our stimulus. We also found that the evoked OKN can serve as a cue
      for accurate estimation about which object image was dominant during rivalry,
      since OKN follows the motion associated with the image in awareness at a given
      time. This novel visual presentation technique enables us to effectively explore
      the neural correlates of visual awareness using animal models.

PMID- 22396466
TI  - Stiles-Crawford effect in focal macular ERGs from macaque monkey.
AB  - BACKGROUND: To determine whether the focal macular electroretinograms (FMERGs)
      are affected by the angle of incidence of the stimulating light on the retina,
      i.e., the Stiles-Crawford effect (SCE). METHODS: FMERGs were elicited by focal
      stimulation of the macula in three light-adapted macaque monkeys. The incidence
      of the light on the retina was varied from 0 to +/-11.7 degrees . The effects of
      the incidence and wavelengths of the stimulus on the SCE were determined.
      RESULTS: The amplitudes of the FMERG components were largest when the stimulus
      beam entered the eye on the visual axis and passed through the center of the
      pupil. The amplitudes gradually decreased as the stimulus beam passed through the
      pupil more eccentrically and fell on the retina more obliquely. All components of
      the FMERGs were decreased with the decrease least for the amplitude of the d
      wave. CONCLUSIONS: The decrease in the amplitudes of the FMERGs as the angle of
      incidence of the stimulus beam on the retina increases demonstrates that the SCE
      can be detected in adult macaque monkeys. This objective method of assessing the
      SCE suggests that this technique can be used to assess the alignment of cones in
      humans with different types of macular diseases.

PMID- 22396467
TI  - Ethnic and social disparity in glycaemic control in type 2 diabetes; cohort study
      in general practice 2004-9.
AB  - OBJECTIVE: To determine whether ethnic group differences in glycated haemoglobin
      (HbA1c) changed over a 5-year period in people on medication for type 2 diabetes.
      DESIGN: Open cohort in 2004-9. SETTING: Electronic records of 100 of the 101
      general practices in two inner London boroughs. PARTICIPANTS: People aged 35 to
      74 years on medication for type 2 diabetes. MAIN OUTCOME MEASURES: Mean HbA1c and
      proportion with HbA1c controlled to <= 7.5%. RESULTS: In this cohort of 24,111
      people, 22% were White, 58% South Asian and 17% Black African/Caribbean. From
      2004 to 2009 mean HbA1c improved from 8.2% to 7.8% for White, from 8.5% to 8.0%
      for Black African/Caribbean and from 8.5% to 8.0% for South Asian people. The
      proportion with HbA1c controlled to 7.5% or less, increased from 44% to 56% in
      White, 38% to 53% in Black African/Caribbean and 34% to 48% in South Asian
      people. Ethnic group and social deprivation were independently associated with
      HbA1c. South Asian and Black African/Caribbean people were treated more
      intensively than White people. CONCLUSION: HbA1c control improved for all ethnic
      groups between 2004-9. However, South Asian and Black African/Caribbean people
      had persistently worse control despite more intensive treatment and significantly
      more improvement than White people. Higher social deprivation was independently
      associated with worse control.

PMID- 22396469
TI  - The aging lung.

PMID- 22396470
TI  - The role of Toll-like receptors in age-associated lung diseases.
AB  - The aging lung is faced with unique challenges. The lungs are the only internal
      organ with a direct interface with both the internal and the external
      environments and as a consequence are constantly sampling diverse, potentially
      injurious, elements. Therefore, the lungs have evolved a sophisticated,
      multilayered detection system to distinguish low-level, nonharmful signals from
      those that are toxic. A family of innate immune receptors, Toll-like receptors
      (TLRs), appears to serve such a function. Initially described as pattern
      recognition receptors that recognize and protect against microbes, TLRs can also
      respond to diverse, nonmicrobial signals. The role of Toll-like receptors in
      noninfectious, age-related chronic lung disease is poorly understood. This review
      presents our current understanding of the biology of age-related lung diseases
      with a focus on the role of Toll-like receptors in idiopathic pulmonary fibrosis,
      chronic obstructive pulmonary disease, and late-onset asthma.

PMID- 22396474
TI  - Social support and mental health in middle-aged men and women: a multidimensional
      approach.
AB  - OBJECTIVE: The purpose of this study is to examine the association between
      various aspects of social support and depressive symptoms separately among men
      and women. METHOD: Using a sample of 6,767 middle-aged adults from one wave of
      the Wisconsin Longitudinal Study (1992-1993), the authors performed a series of
      ANCOVAs predicting depressive symptoms and controlling for background variables.
      RESULTS: The authors found that the receipt of emotional support was associated
      with mental health in women only, whereas the provision of emotional and
      instrumental support was associated with mental health among men and women, but
      with varying patterns. For example, men who provided instrumental support to
      nonkin only had the highest levels of depressive symptoms, whereas women who
      provided instrumental support to kin only had the highest levels of symptoms.
      DISCUSSION: This study helps to clarify if and what types of social support are
      related to mental health in men and women.

PMID- 22396471
TI  - T-cell biology in aging, with a focus on lung disease.
AB  - T cells are essential for defending hosts against microorganisms and malignancy
      as well as for regulating the development of immune-mediated inflammatory
      diseases like autoimmunity. Alterations in T-cell immunity occur with aging,
      affecting the function and proportions of T-cell subsets. Probably, the most
      noticeable age-associated change in T-cell immunity is an alteration in the
      frequency of naive and memory CD4+ and CD8+ T cells. In fact, the frequency of
      naive CD4+ and CD8+ T cells decreases with aging, whereas the frequency of memory
      CD4+ and CD8+ T cells increases. Also, changes in T-cell proliferation, cytokine
      production, memory response, and cytotoxicity as well as in regulatory T-cell
      number and function have been reported with aging. Such alterations could
      contribute to the development of infections, malignancies, and inflammatory
      diseases that rise with aging. Of interest, T cells are closely involved in the
      development of inflammatory airway and lung diseases including asthma and chronic
      obstructive pulmonary disease, which are prevalent in the elderly people. In
      addition, T cells play a major role in defending host against influenza virus
      infection, a serious medical problem with high morbidity and mortality in the
      elderly people. Thus, it is conceivable that altered T-cell immunity may account
      in part for the development of such respiratory problems with aging. Here, we
      will review the recent advances in T-cell immunity and its alteration with aging
      and discuss the potential effects of such changes on the lung.

PMID- 22396472
TI  - Mechanisms of dysfunction in senescent pulmonary endothelium.
AB  - Age-dependent changes in pulmonary endothelium contribute to worsened clinical
      outcomes in elderly individuals. Due to altered pulmonary endothelial responses,
      older participants have increased vulnerability to infection-related sequelae,
      higher prevalence of pulmonary hypertension, mitigated DNA repair mechanisms, and
      attenuated parenchymal healing. Aberrant signaling in pulmonary endothelium
      undergird these clinical processes. In this review, we provide an overview of the
      work that has elucidated age-related molecular derangements in pulmonary
      endothelial cells. In particular, we summarize studies describing mishandling of
      intracellular reactive oxygen species, pathological nitric oxide signaling, and
      deficient recruitment of endothelial stem cell precursors. We conclude with a
      summary of potential future avenues of investigation. The signaling pathways
      associated with pulmonary endothelial senescence reviewed herein suggest a number
      of putative therapeutic drug targets. Further elucidation of the cellular
      processes associated with aging in the pulmonary endothelium may provide critical
      insights into the rational design of therapies that may subvert or even reverse
      the effects of aging on a molecular level.

PMID- 22396475
TI  - Differentiation and visualization of diverse cellular phenotypic responses in
      primary high-content screening.
AB  - High-throughput screening, based on subcellular imaging, has become a powerful
      tool in lead discovery. Through the generation of high-quality images, not only
      the specific target signal can be analyzed but also phenotypic changes of the
      whole cell are recorded. Yet analysis strategies for the exploration of high
      content screening results, in a manner that is independent from predefined
      control phenotypes, are largely missing. The approach presented here is based on
      a well-established modeling technique, self-organizing maps (SOMs), which uses
      multiparametric results to group treatments that create similar morphological
      effects. This report describes a novel visualization of the SOM clustering by
      using an image of the cells from each node, with the most representative cell
      highlighted to deploy the phenotype described by each node. The approach has the
      potential to identify both expected hits and novel cellular phenotypes. Moreover,
      different chemotypes, which cause the same phenotypic effects, are identified,
      thus facilitating "scaffold hopping."

PMID- 22396476
TI  - Diagnostic accuracy of the MMSE in detecting probable and possible Alzheimer's
      disease in ethnically diverse highly educated individuals: an analysis of the
      NACC database.
AB  - BACKGROUND: To validate and extend the findings of a raised cut score of O'Bryant
      and colleagues (O'Bryant SE, Humphreys JD, Smith GE, et al. Detecting dementia
      with the mini-mental state examination in highly educated individuals. Arch
      Neurol. 2008;65(7):963-967.) for the Mini-Mental State Examination in detecting
      cognitive dysfunction in a bilingual sample of highly educated ethnically diverse
      individuals. METHODS: Archival data were reviewed from participants enrolled in
      the National Alzheimer's Coordinating Center minimum data set. Data on 7,093
      individuals with 16 or more years of education were analyzed, including 2,337
      cases with probable and possible Alzheimer's disease, 1,418 mild cognitive
      impairment patients, and 3,088 nondemented controls. Ethnic composition was
      characterized as follows: 6,296 Caucasians, 581 African Americans, 4 American
      Indians or Alaska natives, 2 native Hawaiians or Pacific Islanders, 149 Asians,
      43 "Other," and 18 of unknown origin. RESULTS: Diagnostic accuracy estimates
      (sensitivity, specificity, and likelihood ratio) of Mini-Mental State Examination
      cut scores in detecting probable and possible Alzheimer's disease were examined.
      A standard Mini-Mental State Examination cut score of 24 (<=23) yielded a
      sensitivity of 0.58 and a specificity of 0.98 in detecting probable and possible
      Alzheimer's disease across ethnicities. A cut score of 27 (<=26) resulted in an
      improved balance of sensitivity and specificity (0.79 and 0.90, respectively). In
      the cognitively impaired group (mild cognitive impairment and probable and
      possible Alzheimer's disease), the standard cut score yielded a sensitivity of
      0.38 and a specificity of 1.00 while raising the cut score to 27 resulted in an
      improved balance of 0.59 and 0.96 of sensitivity and specificity, respectively.
      CONCLUSIONS: These findings cross-validate our previous work and extend them to
      an ethnically diverse cohort. A higher cut score is needed to maximize diagnostic
      accuracy of the Mini-Mental State Examination in individuals with college
      degrees.

PMID- 22396477
TI  - Physical activity at age of 20-64 years and mobility and muscle strength in old
      age: a community-based study.
AB  - BACKGROUND: Physical activity in midlife has been related to lower mortality and
      better health in old age. The present study evaluated whether physical activity
      at age of 20-64 years was associated with mobility and muscle strength in old
      age. METHODS: A random sample of 1,000 persons was extracted from all the >=75
      year-old people living in Kuopio, Finland, and 679 community-dwelling
      participants were included in the present analyses. Data on health status,
      ability to walk outside or 400 m, and physical activity level were obtained
      through structured interviews. Participants' walking speed, grip strength, and
      knee extension strength were measured by physiotherapists. Relationship between
      physical activity at age of 20-64 years and old-age mobility and strength was
      assessed using logistic regression and covariance analyses. RESULTS: Of the 679
      participants (mean age 80.8 years), 58.8% had been physically active at age of 20
      64 years. Physical activity at that age was positively associated with ability to
      walk 400 m independently in old age (adjusted odds ratio 2.17, 95% confidence
      intervals: 1.25-3.77). Men who had been physically active at age of 20-64 years
      had greater walking speed (adjusted p = .01) and grip strength (adjusted p = .02)
      compared with physically inactive men. In women, the results did not differ
      statistically significantly. CONCLUSIONS: Physical activity at age of 20-64 years
      was associated with better mobility in old age. It was also linked to better grip
      strength and walking speed in older men but not in women.

PMID- 22396478
TI  - Microdeletion and microduplication syndromes.
AB  - The widespread use of whole genome analysis based on array comparative genomic
      hybridization in diagnostics and research has led to a continuously growing
      number of microdeletion and microduplication syndromes (MMSs) connected to
      certain phenotypes. These MMSs also include increasing instances in which the
      critical region can be reciprocally deleted or duplicated. This review catalogues
      the currently known MMSs and the corresponding critical regions including
      phenotypic consequences. Besides the pathogenic pathways leading to such
      rearrangements, the different detection methods and their limitations are
      discussed. Finally, the databases available for distinguishing between reported
      benign or pathogenic copy number alterations are highlighted. Overall, a review
      of MMSs that previously were also denoted "genomic disorders" or "contiguous gene
      syndromes" is given.

PMID- 22396479
TI  - Local response to microneedle-based influenza immunization in the skin.
AB  - Microneedle patches (MN) provide a novel method of vaccine delivery to the skin
      with the objective of targeting the large network of resident antigen-presenting
      cells to induce an efficient immune response. Our previous reports demonstrated
      that cutaneous delivery of inactivated influenza virus-coated MN to mice protects
      against lethal infection. Protection is correlated with sustained levels of anti
      influenza virus serum antibodies, hemagglutination inhibition titers, and robust
      cellular responses that are often stronger than those generated by intramuscular
      vaccination. Here we dissect the early events occurring in murine skin after
      microneedle delivery of inactivated influenza virus. We demonstrate correlation
      of immunization against influenza virus with a local increase of cytokines
      important for recruitment of neutrophils, monocytes and dendritic cells at the
      site of immunization. We also observed prolonged antigen deposition, and
      migration of matured dendritic cells bearing influenza virus antigen from the
      skin. IMPORTANCE: The immunological mechanisms by which MN vaccination confers
      protective immunity are not well understood. The present study provides a first
      analysis of the early immune events after microneedle-based vaccination.

PMID- 22396481
TI  - Ferret-transmissible influenza A(H5N1) virus: let us err on the side of caution.

PMID- 22396482
TI  - Biosafety considerations of mammalian-transmissible H5N1 influenza.
AB  - The ability to produce an H5N1 influenza virus that can be transmitted from human
      to human raises both biosecurity and biosafety concerns. After analyzing the
      biosafety risks of such a virus, we propose that it be handled at biosafety level
      4 (BSL4) containment until and unless it becomes clear that the risks to humans
      and other mammals can be mitigated.

PMID- 22396480
TI  - Bacteriophages phiMR299-2 and phiNH-4 can eliminate Pseudomonas aeruginosa in the
      murine lung and on cystic fibrosis lung airway cells.
AB  - Pseudomonas aeruginosa is a common cause of infection in the lungs of patients
      with cystic fibrosis (CF). In addition, biofilm formation and antibiotic
      resistance of Pseudomonas are major problems that can complicate antibiotic
      therapy. We evaluated the efficacy of using bacteriophages to kill the pathogen
      in both biofilms and in the murine lung. We isolated and characterized two phages
      from a local wastewater treatment plant, a myovirus (phiNH-4) and a podovirus
      (phiMR299-2). Both phages were active against clinical isolates of P. aeruginosa.
      Together, the two phages killed all 9 clinical isolate strains tested, including
      both mucoid and nonmucoid strains. An equal mixture of the two phages was
      effective in killing P. aeruginosa NH57388A (mucoid) and P. aeruginosa MR299
      (nonmucoid) strains when growing as a biofilm on a cystic fibrosis bronchial
      epithelial CFBE41o- cell line. Phage titers increased almost 100-fold over a 24-h
      period, confirming replication of the phage. Furthermore, the phage mix was also
      effective in killing the pathogen in murine lungs containing 1 * 10(7) to 2 *
      10(7) P. aeruginosa. Pseudomonas was effectively cleared (reduced by a magnitude
      of at least 3 to 4 log units) from murine lungs in 6 h. Our study demonstrates
      the efficacy of these two phages in killing clinical Pseudomonas isolates in the
      murine lung or as a biofilm on a pulmonary cell line and supports the growing
      interest in using phage therapy for the control and treatment of multidrug
      resistant Pseudomonas lung infections in CF patients. IMPORTANCE: Given the rise
      in antibiotic resistance, nonantibiotic therapies are required for the treatment
      of infection. This is particularly true for the treatment of Pseudomonas
      infection in patients with cystic fibrosis. We have identified two bacterial
      viruses (bacteriophages) that can kill Pseudomonas growing on human lung cells
      and in an animal model of lung infection. The use of bacteriophages is
      particularly appropriate because the killing agent can replicate on the target
      cell, generating fresh copies of the bacteriophage. Thus, in the presence of a
      target, the killing agent multiplies. By using two bacteriophages we can reduce
      the risk of resistant colonies developing at the site of infection. Bacteriophage
      therapy is an exciting field, and this study represents an important
      demonstration of efficacy in validated infection models.

PMID- 22396483
TI  - Working safely with H5N1 viruses.
AB  - Research on H5N1 influenza viruses has received much attention recently due to
      the possible dangers associated with newly developed avian H5N1 viruses that were
      derived from highly pathogenic avian viruses and are now transmissible among
      ferrets via respiratory droplets. An appropriate discussion, based on scientific
      facts about the risks that such viruses pose and on the biocontainment facilities
      and practices necessary for working safely with these viruses, is needed.
      Selecting the right level of biocontainment is critical for minimizing the risks
      associated with H5N1 research while simultaneously allowing an appropriately fast
      pace of discovery. Rational countermeasures for preventing the spread of
      influenza can be developed only by gaining a thorough knowledge of the molecular
      mechanisms at work in host specificity and transmission.

PMID- 22396484
TI  - Mammalian-transmissible H5N1 virus: containment level and case fatality ratio.

PMID- 22396485
TI  - Bioinformatics tools and database resources for systems genetics analysis in mice
      -a short review and an evaluation of future needs.
AB  - During a meeting of the SYSGENET working group 'Bioinformatics', currently
      available software tools and databases for systems genetics in mice were reviewed
      and the needs for future developments discussed. The group evaluated
      interoperability and performed initial feasibility studies. To aid future
      compatibility of software and exchange of already developed software modules, a
      strong recommendation was made by the group to integrate HAPPY and R/qtl analysis
      toolboxes, GeneNetwork and XGAP database platforms, and TIQS and xQTL processing
      platforms. R should be used as the principal computer language for QTL data
      analysis in all platforms and a 'cloud' should be used for software dissemination
      to the community. Furthermore, the working group recommended that all data models
      and software source code should be made visible in public repositories to allow a
      coordinated effort on the use of common data structures and file formats.

PMID- 22396486
TI  - LEPSCAN--a web server for searching latent periodicity in DNA sequences.
AB  - A web server for searching latent periodicity based on the method of modified
      profile analysis has been developed. This method allows searching latent
      periodicity in presence of insertions and deletions. During searching process,
      the periodicity classes are used which were found by us earlier for various
      groups of organisms. Period length belongs to the range 2-20 nt, not including
      the triplet periodicity. The results obtained are subjected to various filtration
      steps to ensure their statistical significance. AVAILABILITY: The use of web
      server is free for non-commercial users. No registration is required. URL of the
      server is http://victoria.biengi.ac.ru/lepscan. Current software version is 1.06.

PMID- 22396487
TI  - Biological network motif detection: principles and practice.
AB  - Network motifs are statistically overrepresented sub-structures (sub-graphs) in a
      network, and have been recognized as 'the simple building blocks of complex
      networks'. Study of biological network motifs may reveal answers to many
      important biological questions. The main difficulty in detecting larger network
      motifs in biological networks lies in the facts that the number of possible sub
      graphs increases exponentially with the network or motif size (node counts, in
      general), and that no known polynomial-time algorithm exists in deciding if two
      graphs are topologically equivalent. This article discusses the biological
      significance of network motifs, the motivation behind solving the motif-finding
      problem, and strategies to solve the various aspects of this problem. A simple
      classification scheme is designed to analyze the strengths and weaknesses of
      several existing algorithms. Experimental results derived from a few comparative
      studies in the literature are discussed, with conclusions that lead to future
      research directions.

PMID- 22396488
TI  - Renin and prorenin have no direct effect on aldosterone synthesis in the human
      adrenocortical cell lines H295R and HAC15.
AB  - INTRODUCTION: Transgenic rats expressing the human (pro)renin receptor (h(P)RR)
      have elevated plasma aldosterone levels despite unaltered levels, in plasma and
      adrenal, of renin and angiotensin II. MATERIALS AND METHODS: To investigate
      whether renin/prorenin-(P)RR interaction underlies these elevated aldosterone
      levels, the effect of (pro)renin on steroidogenesis was compared with that of
      angiotensin II in two (P)RR-expressing human adrenocortical cell lines, H295R and
      HAC15. Angiotensin II rapidly induced extracellular signal-regulated kinase (ERK)
      phosphorylation and increased the expression of STAR, CYP21A2, CYP11B2, and
      CYP17A1 at 6 and 24 hours, whereas the expression of CYP11A1 and HSD3B2 remained
      unaltered. Incubation with renin or prorenin at nanomolar concentrations had no
      effect on the expression of any of the steroidogenic enzymes tested, nor resulted
      in ERK phosphorylation. Angiotensin II, but not renin or prorenin, induced
      aldosterone production. CONCLUSION: Although the (P)RR is present in
      adrenocortical cells, renin and prorenin do not elicit ERK phosphorylation nor
      directly affect steroid production via this receptor at nanomolar concentrations.
      Thus, direct (pro)renin-(P)RR interaction is unlikely to contribute to the
      elevated aldosterone levels in human (P)RR transgenic rats. This conclusion also
      implies that the aldosterone rise that often occurs during prolonged renin
      angiotensin system blockade is rather due to the angiotensin II 'escape' during
      such blockade.

PMID- 22396489
TI  - Association of ACE I/D gene polymorphism with vesicoureteral reflux
      susceptibility in children: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Many studies have been conducted to investigate the
      association between angiotensin-converting enzyme (ACE) insertion (I)/deletion
      (D) gene polymorphism and vesicoureteral reflux (VUR) susceptibility. However,
      the results from those studies are still conflicting. We performed a meta
      analysis of studies relating the ACE I/D gene polymorphism to the risk of VUR.
      METHOD: We searched the databases of PubMed, Embase, Cochrane Library and CBM
      disc (China Biological Medicine Database) as of 1 March 2011, and recruited the
      eligible investigations for this meta-analysis. RESULTS: Ten investigations were
      identified for the analysis of association between ACE I/D gene polymorphism and
      VUR risk: six in Caucasians, three in East-Asians and one in a Turkish
      population. All the investigations were performed in children. There was no
      marked association between ACE I/D gene polymorphism and VUR susceptibility/renal
      scar for overall populations, Caucasians and East-Asians. In the Turkish
      population, D allele and DD genotype were associated with the VUR
      susceptibility/renal scar. Furthermore, ACE I/D gene polymorphism was not
      associated with VUR progression. CONCLUSIONS: D allele and DD genotype are risk
      factors for the VUR susceptibility/renal scar in Turkish children. However, more
      case-control association investigations on larger, stratified populations are
      required in the future.

PMID- 22396490
TI  - Impact of intertumoral heterogeneity on predicting chemotherapy response of BRCA1
      deficient mammary tumors.
AB  - The lack of markers to predict chemotherapy responses in patients poses a major
      handicap in cancer treatment. We searched for gene expression patterns that
      correlate with docetaxel or cisplatin response in a mouse model for breast cancer
      associated with BRCA1 deficiency. Array-based expression profiling did not
      identify a single marker gene predicting docetaxel response, despite an increase
      in Abcb1 (P-glycoprotein) expression that was sufficient to explain resistance in
      several poor responders. Intertumoral heterogeneity explained the inability to
      identify a predictive gene expression signature for docetaxel. To address this
      problem, we used a novel algorithm designed to detect differential gene
      expression in a subgroup of the poor responders that could identify tumors with
      increased Abcb1 transcript levels. In contrast, standard analytical tools, such
      as significance analysis of microarrays, detected a marker only if it correlated
      with response in a substantial fraction of tumors. For example, low expression of
      the Xist gene correlated with cisplatin hypersensitivity in most tumors, and it
      also predicted long recurrence-free survival of HER2-negative, stage III breast
      cancer patients treated with intensive platinum-based chemotherapy. Our findings
      may prove useful for selecting patients with high-risk breast cancer who could
      benefit from platinum-based therapy.

PMID- 22396491
TI  - "OA02" peptide facilitates the precise targeting of paclitaxel-loaded micellar
      nanoparticles to ovarian cancer in vivo.
AB  - Micellar nanoparticles based on linear polyethylene glycol (PEG) block dendritic
      cholic acids (CA) copolymers (telodendrimers), for the targeted delivery of
      chemotherapeutic drugs in the treatment of cancers, are reported. The micellar
      nanoparticles have been decorated with a high-affinity "OA02" peptide against
      alpha-3 integrin receptor to improve the tumor-targeting specificity which is
      overexpressed on the surface of ovarian cancer cells. "Click chemistry" was used
      to conjugate alkyne-containing OA02 peptide to the azide group at the distal
      terminus of the PEG chain in a representative PEG(5k)-CA(8) telodendrimer
      (micelle-forming unit). The conjugation of OA02 peptide had negligible influence
      on the physicochemical properties of PEG(5k)-CA(8) nanoparticles and as
      hypothesized, OA02 peptide dramatically enhanced the uptake efficiency of PEG(5k)
      CA(8) nanoparticles (NP) in SKOV-3 and ES-2 ovarian cancer cells via receptor
      mediated endocytosis, but not in alpha-3 integrin-negative K562 leukemia cells.
      When loaded with paclitaxel, OA02-NPs had significantly higher in vitro
      cytotoxicity against both SKOV-3 and ES-2 ovarian cancer cells as compared with
      nontargeted nanoparticles. Furthermore, the in vivo biodistribution study showed
      OA02 peptide greatly facilitated tumor localization and the intracellular uptake
      of PEG(5k)-CA(8) nanoparticles into ovarian cancer cells as validated in SKOV3
      luc tumor-bearing mice. Finally, paclitaxel (PTX)-loaded OA02-NPs exhibited
      superior antitumor efficacy and lower systemic toxicity profile in nude mice
      bearing SKOV-3 tumor xenografts, when compared with equivalent doses of
      nontargeted PTX-NPs as well as clinical paclitaxel formulation (Taxol).
      Therefore, OA02-targeted telodendrimers loaded with paclitaxel have great
      potential as a new therapeutic approach for patients with ovarian cancer.

PMID- 22396492
TI  - Estrogen receptor alpha mediates progestin-induced mammary tumor growth by
      interacting with progesterone receptors at the cyclin D1/MYC promoters.
AB  - Synthetic progesterone used in contraception drugs (progestins) can promote
      breast cancer growth, but the mechanisms involved are unknown. Moreover, it
      remains unclear whether cytoplasmic interactions between the progesterone
      receptor (PR) and estrogen receptor alpha (ERalpha) are required for PR
      activation. In this study, we used a murine progestin-dependent tumor to
      investigate the role of ERalpha in progestin-induced tumor cell proliferation. We
      found that treatment with the progestin medroxyprogesterone acetate (MPA) induced
      the expression and activation of ERalpha, as well as rapid nuclear colocalization
      of activated ERalpha with PR. Treatment with the pure antiestrogen fulvestrant to
      block ERalpha disrupted the interaction of ERalpha and PR in vitro and induced
      the regression of MPA-dependent tumor growth in vivo. ERalpha blockade also
      prevented an MPA-induced increase in CYCLIN D1 (CCND1) and MYC expression.
      Chromatin immunoprecipitation studies showed that MPA triggered binding of
      ERalpha and PR to the CCND1 and MYC promoters. Interestingly, blockade or RNAi
      mediated silencing of ERalpha inhibited ERalpha, but not PR binding to both
      regulatory sequences, indicating that an interaction between ERalpha and PR at
      these sites is necessary for MPA-induced gene expression and cell proliferation.
      We confirmed that nuclear colocalization of both receptors also occurred in human
      breast cancer samples. Together, our findings argued that ERalpha-PR association
      on target gene promoters is essential for progestin-induced cell proliferation.

PMID- 22396493
TI  - Immune response is an important aspect of the antitumor effect produced by a
      CD40L-encoding oncolytic adenovirus.
AB  - Oncolytic adenovirus is an attractive platform for immunotherapy because virus
      replication is highly immunogenic and not subject to tolerance. Although
      oncolysis releases tumor epitopes and provides costimulatory danger signals,
      arming the virus with immunostimulatory molecules can further improve efficacy.
      CD40 ligand (CD40L, CD154) induces apoptosis of tumor cells and triggers several
      immune mechanisms, including a T-helper type 1 (T(H)1) response, which leads to
      activation of cytotoxic T cells and reduction of immunosuppression. In this
      study, we constructed a novel oncolytic adenovirus, Ad5/3-hTERT-E1A-hCD40L, which
      features a chimeric Ad5/3 capsid for enhanced tumor transduction, a human
      telomerase reverse transcriptase (hTERT) promoter for tumor selectivity, and
      human CD40L for increased efficacy. Ad5/3-hTERT-E1A-hCD40L significantly
      inhibited tumor growth in vivo via oncolytic and apoptotic effects, and (Ad5/3
      hTERT-E1A-hCD40L)-mediated oncolysis resulted in enhanced calreticulin exposure
      and HMGB1 and ATP release, which were suggestive of immunogenicity. In two
      syngeneic mouse models, murine CD40L induced recruitment and activation of
      antigen-presenting cells, leading to increased interleukin-12 production in
      splenocytes. This effect was associated with induction of the T(H)1 cytokines IFN
      gamma, RANTES, and TNF-alpha. Tumors treated with Ad5/3-CMV-mCD40L also displayed
      an enhanced presence of macrophages and cytotoxic CD8(+) T cells but not B cells.
      Together, our findings show that adenoviruses coding for CD40L mediate multiple
      antitumor effects including oncolysis, apoptosis, induction of T-cell responses,
      and upregulation of T(H)1 cytokines.

PMID- 22396494
TI  - Genetic ablation of Cav1 differentially affects melanoma tumor growth and
      metastasis in mice: role of Cav1 in Shh heterotypic signaling and
      transendothelial migration.
AB  - Both cell-autonomous and non-cell-autonomous factors contribute to tumor growth
      and metastasis of melanoma. The function of caveolin-1 (Cav1), a multifunctional
      scaffold protein known to modulate several biologic processes in both normal
      tissue and cancer, has been recently investigated in melanoma cancer cells, but
      its role in the melanoma microenvironment remains largely unexplored. Here, we
      show that orthotopic implantation of B16F10 melanoma cells in the skin of Cav1KO
      mice increases tumor growth, and co-injection of Cav1-deficient dermal
      fibroblasts with melanoma cells is sufficient to recapitulate the tumor phenotype
      observed in Cav1KO mice. Using indirect coculture experiments with fibroblasts
      and melanoma cells combined with cytokine analysis, we found that Cav1-deficient
      fibroblasts promoted the growth of melanoma cells via enhanced paracrine cytokine
      signaling. Specifically, Cav1-deficient fibroblasts displayed increased ShhN
      expression, which heterotypically enhanced the Shh signaling pathway in melanoma
      cells. In contrast to primary tumor growth, the ability of B16F10 melanoma cells
      to form lung metastases was significantly reduced in Cav1KO mice. This phenotype
      was associated mechanistically with the inability of melanoma cells to adhere to
      and to transmigrate through a monolayer of endothelial cells lacking Cav1.
      Together, our findings show that Cav1 may regulate different mechanisms during
      primary melanoma tumor growth and metastatic dissemination.

PMID- 22396496
TI  - CD73-deficient mice are resistant to carcinogenesis.
AB  - CD73 is a cell surface 5'-nucleotidase that converts AMP to adenosine, an immune
      suppressive molecule. CD73 may promote immune escape in cancer by contributing to
      the degradation of extracellular ATP released by dying cancer cells in hypoxic
      tumors or following chemotherapy. However, whether CD73 exerts a critical
      oncogenic function during tumorigenesis is unknown. In this study, we used
      genetically deficient mice to investigate its contribution to autochthonous tumor
      formation. CD73 deficiency suppressed the development of 3-methylcholanthrene
      (MCA)-induced fibrosarcomas through a mechanism relying upon IFN-gamma, natural
      killer (NK) cells, and CD8(+) T cells. Similarly, CD73 deficiency also suppressed
      prostate tumorigenesis in TRAMP transgenic mice. Importantly, treatment with an
      anti-CD73 monoclonal antibody effectively suppressed growth of established MCA
      induced tumors or TRAMP-C1 prostate tumors and inhibited the development of TRAMP
      C1 lung metastases. The therapeutic activity of anti-CD73 monoclonal antibody
      against primary tumors was dependent on CD8(+) T cells, whereas its
      antimetastatic activity was dependent on host CD73 expression independent of T
      cells or NK cells. Taken together, our findings indicate that CD73 is a critical
      factor in tumorigenesis and that anti-CD73 antibodies may offer a novel
      generalized strategy to blunt immune escape and treat cancer.

PMID- 22396495
TI  - Defining NOTCH3 target genes in ovarian cancer.
AB  - NOTCH3 gene amplification plays an important role in the progression of many
      ovarian and breast cancers, but the targets of NOTCH3 signaling are unclear.
      Here, we report the use of an integrated systems biology approach to identify
      direct target genes for NOTCH3. Transcriptome analysis showed that suppression of
      NOTCH signaling in ovarian and breast cancer cells led to downregulation of genes
      in pathways involved in cell-cycle regulation and nucleotide metabolism.
      Chromatin immunoprecipitation (ChIP)-on-chip analysis defined promoter target
      sequences, including a new CSL binding motif (N1) in addition to the canonical
      CSL binding motif, that were occupied by the NOTCH3/CSL transcription complex.
      Integration of transcriptome and ChIP-on-chip data showed that the ChIP target
      genes overlapped significantly with the NOTCH-regulated transcriptome in ovarian
      cancer cells. From the set of genes identified, we showed that the mitotic
      apparatus organizing protein DLGAP5 (HURP/DLG7) was a critical target. Both the
      N1 motif and the canonical CSL binding motif were essential to activate DLGAP5
      transcription. DLGAP5 silencing in cancer cells suppressed tumorigenicity and
      inhibited cellular proliferation by arresting the cell cycle at the G(2)-M phase.
      In contrast, enforced expression of DLGAP5 partially counteracted the growth
      inhibitory effects of a pharmacologic or RNA interference-mediated NOTCH
      inhibition in cancer cells. Our findings define direct target genes of NOTCH3 and
      highlight the role of DLGAP5 in mediating the function of NOTCH3.

PMID- 22396497
TI  - Vanilloid receptor-1 regulates neurogenic inflammation in colon and protects mice
      from colon cancer.
AB  - Neuroinflammation driven by the vanilloid-type ion channel receptor transient
      receptor potential vanilloid type 1 (TRPV-1) is suspected to play a role in the
      pathophysiology of inflammatory bowel disease. Because inflammatory bowel disease
      is known to elevate the risk of colon cancer, we examined postulated roles for
      TRPV-1-driven neuroinflammation in promoting colitis-associated and spontaneous
      colon cancer development. Using a well-established model of colitis-associated
      cancer (CAC), we found that mice genetically deficient in TRPV-1 showed a higher
      incidence and number of tumors in the distal colon. In like manner, genetic
      deficiency of TRPV-1 in the APC(Min/+) model of spontaneous colon cancer
      accentuated the number of colonic adenomas formed. Mechanistic analyses in the
      CAC model revealed an increased infiltration of inflammatory cells into the
      tumors along with elevated expression of interleukin (IL)-6 and IL-11 and
      activation of the STAT3 and NF-kappaB signaling pathways. Notably, TPRV-1
      deficient mice exhibited a defect in expression of the anti-inflammatory
      neuropeptides, vasoactive intestinal peptide (VIP), and pituitary adenylate
      cyclase-activating peptide (PACAP) which contributed to the generation of a local
      proinflammatory environment. Together, our findings argue that by limiting
      neuroinflammatory processes, TRPV-1 exerts a protective role that restricts the
      initiation and progression of colon cancer.

PMID- 22396499
TI  - Association of activity changes in the primary sensory cortex with successful
      motor rehabilitation of the hand following stroke.
AB  - BACKGROUND: Previous studies demonstrated a posterior shift of activation toward
      the primary sensory cortex (S1) following stroke; however, any relationship
      between this posterior shift and clinical outcome measures for the affected hand
      function were unclear. OBJECTIVE: The authors investigated the possible role of
      S1 in motor recovery. METHODS: Assuming that previous studies examined
      inhomogeneous groups of patients, the authors selected participants with chronic
      stroke who had moderate hand paresis, normal sensory examination and
      somatosensory-evoked potentials, and no lesion within the S1, thalamus, or brain
      stem. Constraint-induced movement therapy (CIMT) was used to train the impaired
      hand. To relate fMRI (functional MRI) activation changes from baseline to post
      CIMT, a correlation analysis was performed with changes of the Wolf Motor
      Function Test (WMFT) as a test for the hand function. RESULTS: A close
      relationship was found between increases in hand function and peak changes in
      activation within the ipsilesional S1. With a better outcome, greater increases
      in activation within the S1 were evident (P < .03; r = 0.73). CONCLUSION: In
      selected patients, the sensory network influences training-induced motor gains.
      This predictive knowledge of plasticity when applying CIMT may suggest strategies
      to enhance the effect of therapy, such as the addition of electrical stimulation
      to enhance S1 excitability.

PMID- 22396498
TI  - Endothelial expression of TNF receptor-1 generates a proapoptotic signal
      inhibited by integrin alpha6beta1 in glioblastoma.
AB  - Activation of TNF receptor 1 (TNF-R1) can generate signals that promote either
      apoptosis or survival. In this study, we show that these signals can be
      determined by the character of the extracellular matrix in the tumor
      microenvironment. Specifically, through studies of glioblastoma, we showed that
      TNFalpha stimulation induced apoptosis of primary brain endothelial cells (EC)
      attached to collagen or fibronectin (which engage integrins
      alpha2beta1/alpha3beta1 and alpha5beta1, respectively), but did not induce
      apoptosis of ECs attached to laminin (which engages integrins alpha6beta1 and
      alpha3beta1). TNF-R1 expression was significantly higher in ECs in glioblastoma
      (GBM) tumors compared with ECs in normal brain specimens. TNFalpha was also
      expressed in GBM tumor-associated ECs, which was associated with longer patient
      survival. ECs plated on anti-integrin alpha2 or alpha3 antibody were susceptible
      to TNFalpha-induced apoptosis, whereas those plated on anti-integrin alpha6
      antibody were not. Moreover, the ECs plated on laminin, but not collagen,
      expressed cellular FLICE inhibitory protein (cFLIP) and TNFalpha stimulation of
      laminin-attached cells in which cFLIP had been downregulated resulted in the
      induction of apoptosis. In contrast, attachment to laminin did not induce cFLIP
      expression in GBM tumor stem cells. Together, our findings indicate that the
      laminin receptor integrin alpha6beta1 promotes the survival of brain ECs by
      inhibiting prodeath signaling by TNF-R1, in part by inducing cFLIP expression.

PMID- 22396500
TI  - Longitudinal analysis of balance confidence in individuals with stroke using a
      multilevel model for change.
AB  - BACKGROUND: Confidence about balance may be an important factor affecting self
      efficacy for daily activities after stroke. OBJECTIVE: The authors investigated
      whether confidence changes and the parameters that may predict changes in self
      perceived balance within the first year of community reintegration. METHODS: In
      this prospective study, 98 hemiparetic participants who could walk at least 10 m
      independently were assessed 1, 3, 6, and 12 months postdischarge from
      rehabilitation by the Berg Balance Scale, Timed Up and Go, 6-minute walking
      distance, and depression and anxiety scales. The 98 age-/sex-matched controls
      were assessed at enrollment and the same intervals. Multilevel modeling was used
      to determine if assessed covariates predicted changes in balance confidence by
      the Activities-Specific Balance Confidence Scale. RESULTS: Stroke subjects had
      lower initial balance confidence than controls and showed a statistically
      significant increase in confidence over 1 year at each assessment. Poor balance
      and high state anxiety were associated with lower balance confidence. Significant
      interactions were observed between greater depression, along with more impaired
      walking capacity and balance tests, in predicting lower change trajectories in
      confidence. Falls predicted a reduced rate of improvement. CONCLUSIONS: Balance
      confidence after stroke remained lower than controls over the first year.
      Physical therapies and supportive interventions designed to treat confidence
      should be initiated at discharge from inpatient rehabilitation.

PMID- 22396501
TI  - Statin inhibits hypoxia-induced endothelin-1 via accelerated degradation of HIF
      1alpha in vascular smooth muscle cells.
AB  - AIMS: Endothelin-1 (ET-1) contributes to the pathogenesis of cardiovascular
      diseases with multiple properties such as vasoconstriction. Human ET-1 gene
      expression is up-regulated by the transcription factor hypoxia-inducible factor-1
      (HIF-1) through hypoxia response element (HRE). Although previous studies
      suggested that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
      (statins) alter HIF-1-related gene expression, it remained unclear whether
      statins modulate HIF-1-mediated ET-1 expression. Therefore, we investigated the
      effect of fluvastatin on hypoxia-induced human ET-1 expression in vascular smooth
      muscle cells (VSMC). METHODS AND RESULTS: Hypoxia (1% O(2)), compared with the
      normoxic condition (21% O(2)), significantly induced the expression of preproET-1
      mRNA, ET-1 protein, and ET-1 secretion in VSMC. Hypoxia induced a 2.3-fold
      increase in HRE-dependent ET-1 reporter gene activation. Under concentrations of
      1 umol/L or greater, fluvastatin attenuated the hypoxia-induced ET-1 gene
      expression through the accelerated ubiquitin/proteasome-dependent degradation of
      HIF-1alpha, thus consequently attenuating HIF-1alpha binding to the HRE of the ET
      1 gene. These inhibitory effects of fluvastatin were cancelled by concomitant
      treatment with mevalonate, farnesyl pyrophosphate, or geranylgeranyl
      pyrophosphate, but not squalene. CONCLUSION: The present study suggests that
      fluvastatin attenuates HIF-1-dependent ET-1 gene expression in conjunction with
      the stimulation of HIF-1alpha ubiquitin/proteasome-dependent degradation via
      isoprenoid-dependent mechanisms.

PMID- 22396502
TI  - The cover. Isaac Josiah and William Mulford Hand.

PMID- 22396503
TI  - Some question use of statins to reduce cardiovascular risks in healthy women.

PMID- 22396504
TI  - Effects of FDA safety warnings may vary.

PMID- 22396505
TI  - Movement to promote good stewardship of medical resources gains momentum.

PMID- 22396506
TI  - Evaluation for coronary artery disease and medicare spending.

PMID- 22396507
TI  - Evaluation for coronary artery disease and medicare spending.

PMID- 22396508
TI  - Prescription drug monitoring programs.

PMID- 22396509
TI  - The Affordable Care Act and insurance coverage for young adults.

PMID- 22396510
TI  - The retreat from advanced care planning.

PMID- 22396511
TI  - Time to revise the approach to determining cardiopulmonary resuscitation status.

PMID- 22396512
TI  - Seven provocative principles for health care reform.

PMID- 22396513
TI  - A piece of my mind. The before.

PMID- 22396514
TI  - Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized
      trial.
AB  - CONTEXT: Despite reported success, surgery for pharmacoresistant seizures is
      often seen as a last resort. Patients are typically referred for surgery after 20
      years of seizures, often too late to avoid significant disability and premature
      death. OBJECTIVE: We sought to determine whether surgery soon after failure of 2
      antiepileptic drug (AED) trials is superior to continued medical management in
      controlling seizures and improving quality of life (QOL). DESIGN, SETTING, AND
      PARTICIPANTS: The Early Randomized Surgical Epilepsy Trial (ERSET) is a
      multicenter, controlled, parallel-group clinical trial performed at 16 US
      epilepsy surgery centers. The 38 participants (18 men and 20 women; aged >=12
      years) had mesial temporal lobe epilepsy (MTLE) and disabling seizues for no more
      than 2 consecutive years following adequate trials of 2 brand-name AEDs.
      Eligibility for anteromesial temporal resection (AMTR) was based on a
      standardized presurgical evaluation protocol. Participants were randomized to
      continued AED treatment or AMTR 2003-2007, and observed for 2 years. Planned
      enrollment was 200, but the trial was halted prematurely due to slow accrual.
      INTERVENTION: Receipt of continued AED treatment (n = 23) or a standardized AMTR
      plus AED treatment (n = 15). In the medical group, 7 participants underwent AMTR
      prior to the end of follow-up and 1 participant in the surgical group never
      received surgery. MAIN OUTCOME MEASURES: The primary outcome variable was freedom
      from disabling seizures during year 2 of follow-up. Secondary outcome variables
      were health-related QOL (measured primarily by the 2-year change in the Quality
      of Life in Epilepsy 89 [QOLIE-89] overall T-score), cognitive function, and
      social adaptation. RESULTS: Zero of 23 participants in the medical group and 11
      of 15 in the surgical group were seizure free during year 2 of follow-up (odds
      ratio = infinity; 95% CI, 11.8 to infinity; P < .001). In an intention-to-treat
      analysis, the mean improvement in QOLIE-89 overall T-score was higher in the
      surgical group than in the medical group but this difference was not
      statistically significant (12.6 vs 4.0 points; treatment effect = 8.5; 95% CI, 
      1.0 to 18.1; P = .08). When data obtained after surgery from participants in the
      medical group were excluded, the effect of surgery on QOL was significant (12.8
      vs 2.8 points; treatment effect = 9.9; 95% CI, 2.2 to 17.7; P = .01). Memory
      decline (assessed using the Rey Auditory Verbal Learning Test) occurred in 4
      participants (36%) after surgery, consistent with rates seen in the literature;
      but the sample was too small to permit definitive conclusions about treatment
      group differences in cognitive outcomes. Adverse events included a transient
      neurologic deficit attributed to a magnetic resonance imaging-identified
      postoperative stroke in a participant who had surgery and 3 cases of status
      epilepticus in the medical group. CONCLUSIONS: Among patients with newly
      intractable disabling MTLE, resective surgery plus AED treatment resulted in a
      lower probability of seizures during year 2 of follow-up than continued AED
      treatment alone. Given the premature termination of the trial, the results should
      be interpreted with appropriate caution. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00040326.

PMID- 22396516
TI  - Association of mental health disorders with prescription opioids and high-risk
      opioid use in US veterans of Iraq and Afghanistan.
AB  - CONTEXT: Record numbers of Iraq and Afghanistan veterans survive their war
      injuries and yet continue to experience pain and mental health problems,
      particularly posttraumatic stress disorder (PTSD). Little is known about the
      association of mental health disorders and prescription opioid use. OBJECTIVE: To
      investigate the effect of mental health disorders, particularly PTSD, on risks
      and adverse clinical outcomes associated with prescription opioid use. DESIGN:
      Retrospective cohort study involving 141,029 Iraq and Afghanistan veterans who
      received at least 1 non-cancer-related pain diagnosis within 1 year of entering
      the Department of Veterans Affairs (VA) health care system from October 1, 2005,
      through December 31, 2010. MAIN OUTCOME MEASURES: Independent association of
      mental health disorders and the prescription of opioids, higher risk opioid use,
      and adverse clinical outcomes (eg, accidents and overdose) within 1 year of
      receiving a pain-related diagnosis. RESULTS: A total of 15,676 veterans were
      prescribed opioids within 1 year of their initial pain diagnosis. Compared with
      6.5% of veterans without mental health disorders, 17.8% (adjusted relative risk
      [RR], 2.58; 95% CI, 2.49-2.67) of veterans with PTSD and 11.7% (adjusted RR,
      1.74; 95% CI, 1.67-1.82) with other mental health diagnoses but without PTSD were
      significantly more likely to receive opioids for pain diagnoses. Of those who
      were prescribed pain medication, veterans with PTSD were more likely than those
      without mental health disorders to receive higher-dose opioids (22.7% vs 15.9%,
      adjusted RR, 1.42; 95% CI, 1.31-1.54), receive 2 or more opioids concurrently
      (19.8% vs 10.7%, adjusted RR, 1.87; 95% CI, 1.70-2.06), receive sedative
      hypnotics concurrently (40.7% vs 7.6%, adjusted RR, 5.46; 95% CI, 4.91-6.07), or
      obtain early opioid refills (33.8% vs 20.4%; adjusted RR, 1.64; 95% CI, 1.53
      1.75). Receiving prescription opioids (vs not) was associated with an increased
      risk of adverse clinical outcomes for all veterans (9.5% vs 4.1%; RR, 2.33; 95%
      CI, 2.20-2.46), which was most pronounced in veterans with PTSD. CONCLUSION:
      Among US veterans of Iraq and Afghanistan, mental health diagnoses, especially
      PTSD, were associated with an increased risk of receiving opioids for pain, high
      risk opioid use, and adverse clinical outcomes.

PMID- 22396515
TI  - Effect of testosterone supplementation with and without a dual 5alpha-reductase
      inhibitor on fat-free mass in men with suppressed testosterone production: a
      randomized controlled trial.
AB  - CONTEXT: Steroid 5alpha-reductase inhibitors are used to treat benign prostatic
      hyperplasia and androgenic alopecia, but the role of 5alpha-dihydrotestosterone
      (DHT) in mediating testosterone's effects on muscle, sexual function,
      erythropoiesis, and other androgen-dependent processes remains poorly understood.
      OBJECTIVE: To determine whether testosterone's effects on muscle mass, strength,
      sexual function, hematocrit level, prostate volume, sebum production, and lipid
      levels are attenuated when its conversion to DHT is blocked by dutasteride (an
      inhibitor of 5alpha-reductase type 1 and 2). DESIGN, SETTING, AND PATIENTS: The
      5alpha-Reductase Trial was a randomized controlled trial of healthy men aged 18
      to 50 years comparing placebo plus testosterone enthanate with dutasteride plus
      testosterone enanthate from May 2005 through June 2010. INTERVENTIONS: Eight
      treatment groups received 50, 125, 300, or 600 mg/wk of testosterone enanthate
      for 20 weeks plus placebo (4 groups) or 2.5 mg/d of dutasteride (4 groups). MAIN
      OUTCOME MEASURES: The primary outcome was change in fat-free mass; secondary
      outcomes: changes in fat mass, muscle strength, sexual function, prostate volume,
      sebum production, and hematocrit and lipid levels. RESULTS: A total of 139 men
      were randomized; 102 completed the 20-week intervention. Men assigned to
      dutasteride were similar at baseline to those assigned to placebo. The mean fat
      free mass gained by the dutasteride groups was 0.6 kg (95% CI, -0.1 to 1.2 kg)
      when receiving 50 mg/wk of testosterone enanthate, 2.6 kg (95% CI, 0.9 to 4.3 kg)
      for 125 mg/wk, 5.8 kg (95% CI, 4.8 to 6.9 kg) for 300 mg/wk, and 7.1 kg (95% CI,
      6.0 to 8.2 kg) for 600 mg/wk. The mean fat-free mass gained by the placebo groups
      was 0.8 kg (95% CI, -0.1 to 1.7 kg) when receiving 50 mg/wk of testosterone
      enanthate, 3.5 kg (95% CI, 2.1 to 4.8 kg) for 125 mg/wk, 5.7 kg (95% CI, 4.8 to
      6.5 kg) for 300 mg/wk, and 8.1 kg (95% CI, 6.7 to 9.5 kg) for 600 mg/wk. The dose
      adjusted differences between the dutasteride and placebo groups for fat-free mass
      were not significant (P = .18). Changes in fat mass, muscle strength, sexual
      function, prostate volume, sebum production, and hematocrit and lipid levels did
      not differ between groups. CONCLUSION: Changes in fat-free mass in response to
      graded testosterone doses did not differ in men in whom DHT was suppressed by
      dutasteride from those treated with placebo, indicating that conversion of
      testosterone to DHT is not essential for mediating its anabolic effects on
      muscle. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00493987.

PMID- 22396517
TI  - Bevacizumab in patients with hereditary hemorrhagic telangiectasia and severe
      hepatic vascular malformations and high cardiac output.
AB  - CONTEXT: The only treatment available to restore normal cardiac output in
      patients with hereditary hemorrhagic telangiectasia (HHT) and cardiac failure is
      liver transplant. Anti-vascular endothelial growth factor treatments such as
      bevacizumab may be an effective treatment. OBJECTIVES: To test the efficacy of
      bevacizumab in reducing high cardiac output in severe hepatic forms of HHT and to
      assess improvement in epistaxis duration and quality of life. DESIGN, SETTING,
      AND PATIENTS: Single-center, phase 2 trial with national recruitment from the
      French HHT Network. Patients were 18 to 70 years old and had confirmed HHT,
      severe liver involvement, and a high cardiac index related to HHT. INTERVENTION:
      Bevacizumab, 5 mg per kg, every 14 days for a total of 6 injections. The total
      duration of the treatment was 2.5 months; patients were followed up for 6 months
      after the beginning of the treatment. MAIN OUTCOME MEASURE: Decrease in cardiac
      output at 3 months after the first injection, evaluated by echocardiography.
      RESULTS: A total of 25 patients were included between March 2009 and November
      2010. Of the 24 patients who had echocardiograms available for reread, there was
      a response in 20 of 24 patients with normalization of cardiac index (complete
      response [CR]) in 3 of 24, partial response (PR) in 17 of 24, and no response in
      4 cases. Median cardiac index at beginning of the treatment was 5.05 L/min/m(2)
      (range, 4.1-6.2) and significantly decreased at 3 months after the beginning of
      the treatment with a median cardiac index of 4.2 L/min/m(2) (range, 2.9-5.2; P <
      .001). Median cardiac index at 6 months was significantly lower than before
      treatment (4.1 L/min/m(2); range, 3.0-5.1). Among 23 patients with available data
      at 6 months, we observed CR in 5 cases, PR in 15 cases, and no response in 3
      cases. Mean duration of epistaxis, which was 221 minutes per month (range, 0-947)
      at inclusion, had significantly decreased at 3 months (134 minutes; range, 0-656)
      and 6 months (43 minutes; range, 0-310) (P = .008). Quality of life had
      significantly improved. The most severe adverse events were 2 cases of grade 3
      systemic hypertension, which were successfully treated. CONCLUSION: In this
      preliminary study of patients with HHT associated with severe hepatic vascular
      malformations and high cardiac output, administration of bevacizumab was
      associated with a decrease in cardiac output and reduced duration and number of
      episodes of epistaxis. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00843440.

PMID- 22396518
TI  - Update: A 37-year-old man trying to choose a high-quality hospital: review of
      hospital quality indicators.

PMID- 22396519
TI  - Stopping seizures early and the surgical epilepsy trial that stopped even
      earlier.

PMID- 22396520
TI  - The role of 5alpha-reductase inhibition in men receiving testosterone replacement
      therapy.

PMID- 22396521
TI  - JAMA patient page. Epilepsy surgery.

PMID- 22396522
TI  - Tax needn't be taxing, but in the case of organ donation it might be.
AB  - Petersen and Lippert-Rasmussen argue that, while a tax credit scheme to encourage
      organ donation would be costly, the increased number of organs for
      transplantation would lead to other savings in the healthcare system. In the
      present work some calculations are provided and it is suggested that, even given
      optimistic assumptions, the cost to the state of implementing the system as
      proposed would be high and unlikely to garner the support of politicians and
      policymakers.

PMID- 22396523
TI  - Evolution of the voltage sensor domain of the voltage-sensitive phosphoinositide
      phosphatase VSP/TPTE suggests a role as a proton channel in eutherian mammals.
AB  - The voltage-sensitive phosphoinositide phosphatases provide a mechanism to couple
      changes in the transmembrane electrical potential to intracellular signal
      transduction pathways. These proteins share a domain architecture that is
      conserved in deuterostomes. However, gene duplication events in primates,
      including humans, give rise to the paralogs TPTE and TPTE2 that retain protein
      domain organization but, in the case of TPTE, have lost catalytic activity. Here,
      we present evidence that these human proteins contain a functional voltage
      sensor, similar to that in nonmammalian orthologs. However, domains of these
      human proteins can also generate a noninactivating outward current that is not
      observed in zebra fish or tunicate orthologs. This outward current has the
      anticipated characteristics of a voltage-sensitive proton current and is due to
      the appearance of a single histidine residue in the S4 transmembrane segment of
      the voltage sensor. Histidine is observed at this position only during the
      eutherian radiation. Domains from both human paralogs generate proton currents.
      This apparent gain of proton channel function during the evolution of the TPTE
      protein family may account for the conservation of voltage sensor domains despite
      the loss of phosphatase activity in some human paralogs.

PMID- 22396524
TI  - The Plasmodium apicoplast genome: conserved structure and close relationship of
      P. ovale to rodent malaria parasites.
AB  - Apicoplast, a nonphotosynthetic plastid derived from secondary symbiotic origin,
      is essential for the survival of malaria parasites of the genus Plasmodium.
      Elucidation of the evolution of the apicoplast genome in Plasmodium species is
      important to better understand the functions of the organelle. However, the
      complete apicoplast genome is available for only the most virulent human malaria
      parasite, Plasmodium falciparum. Here, we obtained the near-complete apicoplast
      genome sequences from eight Plasmodium species that infect a wide variety of
      vertebrate hosts and performed structural and phylogenetic analyses. We found
      that gene repertoire, gene arrangement, and other structural attributes were
      highly conserved. Phylogenetic reconstruction using 30 protein-coding genes of
      the apicoplast genome inferred, for the first time, a close relationship between
      P. ovale and rodent parasites. This close relatedness was robustly supported
      using multiple evolutionary assumptions and models. The finding suggests that an
      ancestral host switch occurred between rodent and human Plasmodium parasites.

PMID- 22396525
TI  - Protein conformational diversity modulates sequence divergence.
AB  - It is well established that the conservation of protein structure during
      evolution constrains sequence divergence. The conservation of certain
      physicochemical environments to preserve protein folds and then the biological
      function originates a site-specific structurally constrained substitution
      pattern. However, protein native structure is not unique. It is known that the
      native state is better described by an ensemble of conformers in a dynamic
      equilibrium. In this work, we studied the influence of conformational diversity
      in sequence divergence and protein evolution. For this purpose, we derived a set
      of 900 proteins with different degrees of conformational diversity from the PCDB
      database, a conformer database. With the aid of a structurally constrained
      protein evolutionary model, we explored the influence of the different
      conformations on sequence divergence. We found that the presence of
      conformational diversity strongly modulates the substitution pattern. Although
      the conformers share several of the structurally constrained sites, 30% of them
      are conformer specific. Also, we found that in 76% of the proteins studied, a
      single conformer outperforms the others in the prediction of sequence divergence.
      It is interesting to note that this conformer is usually the one that binds
      ligands participating in the biological function of the protein. The existence of
      a conformer-specific site-substitution pattern indicates that conformational
      diversity could play a central role in modulating protein evolution. Furthermore,
      our findings suggest that new evolutionary models and bioinformatics tools should
      be developed taking into account this substitution bias.

PMID- 22396526
TI  - Related haloarchaeal pleomorphic viruses contain different genome types.
AB  - Archaeal viruses have been the subject of recent interest due to the diversity
      discovered in their virion architectures. Recently, a new group of haloarchaeal
      pleomorphic viruses has been discovered. It is distinctive in terms of the virion
      morphology and different genome types (ssDNA/dsDNA) harboured by rather closely
      related representatives. To date there are seven isolated viruses belonging to
      this group. Most of these share a cluster of five conserved genes, two of which
      encode major structural proteins. Putative proviruses and proviral remnants
      containing homologues of the conserved gene cluster were also identified
      suggesting a long-standing relationship of these viruses with their hosts.
      Comparative genomic analysis revealed three different ways of the genome
      organization, which possibly reflect different replication strategies employed by
      these viruses. The dsDNA genomes of two of these viruses were shown to contain
      single-strand interruptions. Further studies on one of the genomes suggested that
      the interruptions are located along the genome in a sequence-specific manner and
      exhibit polarity in distribution.

PMID- 22396527
TI  - Architecture of the trypanosome RNA editing accessory complex, MRB1.
AB  - Trypanosoma brucei undergoes an essential process of mitochondrial uridine
      insertion and deletion RNA editing catalyzed by a 20S editosome. The multiprotein
      mitochondrial RNA-binding complex 1 (MRB1) is emerging as an equally essential
      component of the trypanosome RNA editing machinery, with additional functions in
      gRNA and mRNA stabilization. The distinct and overlapping protein compositions of
      reported MRB1 complexes and diverse MRB1 functions suggest that the complex is
      composed of subcomplexes with RNA-dependent and independent interactions. To
      determine the architecture of the MRB1 complex, we performed a comprehensive
      yeast two-hybrid analysis of 31 reported MRB1 proteins. We also used in vivo
      analyses of tagged MRB1 components to confirm direct and RNA-mediated
      interactions. Here, we show that MRB1 contains a core complex comprised of six
      proteins and maintained by numerous direct interactions. The MRB1 core associates
      with multiple subcomplexes and proteins through RNA-enhanced or RNA-dependent
      interactions. These findings provide a framework for interpretation of previous
      functional studies and suggest that MRB1 is a dynamic complex that coordinates
      various aspects of mitochondrial gene regulation.

PMID- 22396528
TI  - Inhibition of the function of class IIa HDACs by blocking their interaction with
      MEF2.
AB  - Enzymes that modify the epigenetic status of cells provide attractive targets for
      therapy in various diseases. The therapeutic development of epigenetic
      modulators, however, has been largely limited to direct targeting of catalytic
      active site conserved across multiple members of an enzyme family, which
      complicates mechanistic studies and drug development. Class IIa histone
      deacetylases (HDACs) are a group of epigenetic enzymes that depends on
      interaction with Myocyte Enhancer Factor-2 (MEF2) for their recruitment to
      specific genomic loci. Targeting this interaction presents an alternative
      approach to inhibiting this class of HDACs. We have used structural and
      functional approaches to identify and characterize a group of small molecules
      that indirectly target class IIa HDACs by blocking their interaction with MEF2 on
      DNA.Weused X-ray crystallography and (19)F NMRto show that these compounds
      directly bind to MEF2. We have also shown that the small molecules blocked the
      recruitment of class IIa HDACs to MEF2-targeted genes to enhance the expression
      of those targets. These compounds can be used as tools to study MEF2 and class
      IIa HDACs in vivo and as leads for drug development.

PMID- 22396529
TI  - Crosslinking-MS analysis reveals RNA polymerase I domain architecture and basis
      of rRNA cleavage.
AB  - RNA polymerase (Pol) I contains a 10-subunit catalytic core that is related to
      the core of Pol II and includes subunit A12.2. In addition, Pol I contains the
      heterodimeric subcomplexes A14/43 and A49/34.5, which are related to the Pol II
      subcomplex Rpb4/7 and the Pol II initiation factor TFIIF, respectively. Here we
      used lysine-lysine crosslinking, mass spectrometry (MS) and modeling based on
      five crystal structures, to extend the previous homology model of the Pol I core,
      to confirm the location of A14/43 and to position A12.2 and A49/34.5 on the core.
      In the resulting model of Pol I, the C-terminal ribbon (C-ribbon) domain of A12.2
      reaches the active site via the polymerase pore, like the C-ribbon of the Pol II
      cleavage factor TFIIS, explaining why the intrinsic RNA cleavage activity of Pol
      I is strong, in contrast to the weak cleavage activity of Pol II. The A49/34.5
      dimerization module resides on the polymerase lobe, like TFIIF, whereas the A49
      tWH domain resides above the cleft, resembling parts of TFIIE. This indicates
      that Pol I and also Pol III are distantly related to a Pol II-TFIIS-TFIIF-TFIIE
      complex.

PMID- 22396530
TI  - Activation of natural killer T cells promotes M2 Macrophage polarization in
      adipose tissue and improves systemic glucose tolerance via interleukin-4 (IL
      4)/STAT6 protein signaling axis in obesity.
AB  - Natural killer T (NKT) cells are important therapeutic targets in various disease
      models and are under clinical trials for cancer patients. However, their function
      in obesity and type 2 diabetes remains unclear. Our data show that adipose
      tissues of both mice and humans contain a population of type 1 NKT cells, whose
      abundance decreases with increased adiposity and insulin resistance. Although
      loss-of-function of NKT cells had no effect on glucose tolerance in animals with
      prolonged high fat diet feeding, activation of NKT cells by lipid agonist alpha
      galactosylceramide enhances alternative macrophage polarization in adipose tissue
      and improves glucose homeostasis in animals at different stages of obesity.
      Furthermore, the effect of NKT cells is largely mediated by the IL-4/STAT6
      signaling axis in obese adipose tissue. Thus, our data identify a novel
      therapeutic target for the treatment of obesity-associated inflammation and type
      2 diabetes.

PMID- 22396532
TI  - The role of CD38 in Fcgamma receptor (FcgammaR)-mediated phagocytosis in murine
      macrophages.
AB  - Phagocytosis is a crucial event in the immune system that allows cells to engulf
      and eliminate pathogens. This is mediated through the action of immunoglobulin
      (IgG)-opsonized microbes acting on Fcgamma receptors (FcgammaR) on macrophages,
      which results in sustained levels of intracellular Ca(2+) through the
      mobilization of Ca(2+) second messengers. It is known that the ADP-ribosyl
      cyclase is responsible for the rise in Ca(2+) levels after FcgammaR activation.
      However, it is unclear whether and how CD38 is involved in FcgammaR-mediated
      phagocytosis. Here we show that CD38 is recruited to the forming phagosomes
      during phagocytosis of IgG-opsonized particles and produces cyclic-ADP-ribose,
      which acts on ER Ca(2+) stores, thus allowing an increase in FcgammaR activation
      mediated phagocytosis. Ca(2+) data show that pretreatment of J774A.1 macrophages
      with 8-bromo-cADPR, ryanodine, blebbistatin, and various store-operated Ca(2+)
      inhibitors prevented the long-lasting Ca(2+) signal, which significantly reduced
      the number of ingested opsonized particles. Ex vivo data with macrophages
      extracted from CD38(-/-) mice also shows a reduced Ca(2+) signaling and
      phagocytic index. Furthermore, a significantly reduced phagocytic index of
      Mycobacterium bovis BCG was shown in macrophages from CD38(-/-) mice in vivo.
      This study suggests a crucial role of CD38 in FcgammaR-mediated phagocytosis
      through its recruitment to the phagosome and mobilization of cADPR-induced
      intracellular Ca(2+) and store-operated extracellular Ca(2+) influx.

PMID- 22396534
TI  - Recognition-dependent signaling events in response to apoptotic targets inhibit
      epithelial cell viability by multiple mechanisms: implications for non-immune
      tissue homeostasis.
AB  - Apoptosis allows for the removal of damaged, aged, and/or excess cells without
      harm to surrounding tissue. To accomplish this, cells undergoing apoptosis
      acquire new activities that enable them to modulate the fate and function of
      nearby cells. We have shown that receptor-mediated recognition of apoptotic
      versus necrotic target cells by viable kidney proximal tubular epithelial cells
      (PTEC) modulates the activity of several signaling pathways critically involved
      in regulation of proliferation and survival. Generally, apoptotic and necrotic
      targets have opposite effects with apoptotic targets inhibiting and necrotic
      targets stimulating the activity of these pathways. Here we explore the
      consequences of these signaling differences. We show that recognition of
      apoptotic targets induces a profound decrease in PTEC viability through increased
      responder cell death and decreased proliferation. In contrast, necrotic targets
      promote viability through decreased death and increased proliferation. Both
      target types mediate their effects through a network of Akt-dependent and 
      independent events. Apoptotic targets modulate Akt-dependent viability in part
      through a reduction in cellular beta-catenin and decreased inactivation of Bad.
      In contrast, Akt-independent modulation of viability occurs through activation of
      caspase-8, suggesting that death receptor-dependent pathways are involved.
      Apoptotic targets also activate p38, which partially protects responders from
      target-induced death. The response of epithelial cells varies depending on their
      tissue origin. Some cell lines, like PTEC, demonstrate decreased viability,
      whereas others (e.g. breast-derived) show increased viability. By acting as
      sentinels of environmental change, apoptotic targets allow neighboring cells,
      especially non-migratory epithelial cells, to monitor and potentially adapt to
      local stresses.

PMID- 22396533
TI  - Additive effects of mitochondrion-targeted cytochrome CYP2E1 and alcohol toxicity
      on cytochrome c oxidase function and stability of respirosome complexes.
AB  - Alcohol treatment induces oxidative stress by a combination of increased
      production of partially reduced oxygen species and decreased cellular antioxidant
      pool, including GSH. Recently, we showed that mitochondrion-targeted CYP2E1
      augments alcohol-mediated toxicity, causing an increase in reactive oxygen
      species production and oxidative stress. Here, we show that cytochrome c oxidase
      (CcO), the terminal oxidase of the mitochondrial respiratory chain, is a critical
      target of CYP2E1-mediated alcohol toxicity. COS-7 and Hep G2 cell lines
      expressing predominantly mitochondrion-targeted (Mt(++)) CYP2E1 and livers from
      alcohol-treated rats showed loss of CcO activity and increased protein
      carbonylation, which was accompanied by a decline in the steady state levels of
      subunits I, IVI1, and Vb of the CcO complex. This was also accompanied by reduced
      mitochondrial DNA content and reduced mitochondrial mRNA. These changes were more
      prominent in Mt(++) cells in comparison with wild type (WT) CYP2E1-expressing or
      ER(+) (mostly microsome-targeted) cells. In addition, mitochondrion-specific
      antioxidants, ubiquinol conjugated to triphenyl phosphonium, triphenylphosphonium
      conjugated carboxyl proxyl, and the CYP2E1 inhibitor diallyl sulfide prevented
      the loss of CcO activity and the CcO subunits, most likely through reduced
      oxidative damage to the enzyme complex. Our results suggest that damage to CcO
      and dissociation of respirosome complexes are critical factors in alcohol-induced
      toxicity, which is augmented by mitochondrion-targeted CYP2E1. We propose that
      CcO is one of the direct and immediate targets of alcohol-induced toxicity
      causing respiratory dysfunction.

PMID- 22396535
TI  - Evolutionarily conserved paired immunoglobulin-like receptor alpha (PILRalpha)
      domain mediates its interaction with diverse sialylated ligands.
AB  - Paired immunoglobulin-like receptor (PILR) alpha is an inhibitory receptor that
      recognizes several ligands, including mouse CD99, PILR-associating neural
      protein, and Herpes simplex virus-1 glycoprotein B. The physiological function(s)
      of interactions between PILRalpha and its cellular ligands are not well
      understood, as are the molecular determinants of PILRalpha/ligand interactions.
      To address these uncertainties, we sought to identify additional PILRalpha
      ligands and further define the molecular basis for PILRalpha/ligand interactions.
      Here, we identify two novel PILRalpha binding partners, neuronal differentiation
      and proliferation factor-1 (NPDC1), and collectin-12 (COLEC12). We find that
      sialylated O-glycans on these novel PILRalpha ligands, and on known PILRalpha
      ligands, are compulsory for PILRalpha binding. Sialylation-dependent ligand
      recognition is also a property of SIGLEC1, a member of the sialic acid-binding Ig
      like lectins. SIGLEC1 Ig domain shares ~22% sequence identity with PILRalpha, an
      identity that includes a conserved arginine localized to position 97 in mouse and
      human SIGLEC1, position 133 in mouse PILRalpha and position 126 in human
      PILRalpha. We observe that PILRalpha/ligand interactions require conserved
      PILRalpha Arg-133 (mouse) and Arg-126 (human), in correspondence with a
      previously reported requirement for SIGLEC1 Arg-197 in SIGLEC1/ligand
      interactions. Homology modeling identifies striking similarities between
      PILRalpha and SIGLEC1 ligand binding pockets as well as at least one set of
      distinctive interactions in the galactoxyl-binding site. Binding studies suggest
      that PILRalpha recognizes a complex ligand domain involving both sialic acid and
      protein motif(s). Thus, PILRalpha is evolved to engage multiple ligands with
      common molecular determinants to modulate myeloid cell functions in anatomical
      settings where PILRalpha ligands are expressed.

PMID- 22396536
TI  - Activated apoptotic cells induce dendritic cell maturation via engagement of Toll
      like receptor 4 (TLR4), dendritic cell-specific intercellular adhesion molecule 3
      (ICAM-3)-grabbing nonintegrin (DC-SIGN), and beta2 integrins.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells playing a central
      role in connecting innate and adaptive immunity. Maturation signals are, however,
      required for DCs to undergo phenotypic and functional changes to acquire a fully
      competent antigen-presenting capacity. We previously reported that activated
      apoptotic peripheral lymphocytes (ActApo) provide activation/maturation signals
      to human monocyte-derived DCs. In this paper, we have characterized the signaling
      pathways and molecules involved in ActApo-mediated DC maturation. We found that
      both cellular and supernatant fractions from ActApo are required for DC
      maturation signaling. ActApoSup-induced CD80 and CD86 expression was
      significantly blocked in the presence of neutralizing antibodies against tumor
      necrosis factor-alpha (TNF-alpha). Cell-cell contact-dependent signaling involved
      beta2 integrins, dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN),
      and TLR4 because ActApo-induced up-regulation of the maturation markers CD80 and
      CD86 was significantly inhibited in the presence of neutralizing antibodies
      against CD18, CD11a, CD11b, and DC-SIGN as well as TLR4. The role of TLR4 was
      further confirmed by silencing of TLR4 in DCs. In addition, the endogenous
      adjuvant effect exerted by activated apoptotic splenocytes (ActApoSp) was reduced
      after immunization with human serum albumin in TLR4(-/-) mice. We detected
      activation of multiple signaling pathways and transcription factors in DCs upon
      co-culture with ActApo, including p38, JNK, PI3K-Akt, Src family kinases,
      NFkappaB p65, and AP1 transcription factor family members c-Jun and c-Fos,
      demonstrating the complex interactions occurring between ActApo and DCs. These
      studies provide important mechanistic insight into the responses of DCs during
      encounter with cells undergoing immunogenic cell death.

PMID- 22396537
TI  - Multifunction protein staphylococcal nuclease domain containing 1 (SND1) promotes
      tumor angiogenesis in human hepatocellular carcinoma through novel pathway that
      involves nuclear factor kappaB and miR-221.
AB  - Staphylococcal nuclease domain-containing 1 (SND1) is a multifunctional protein
      that is overexpressed in multiple cancers, including hepatocellular carcinoma
      (HCC). Stable overexpression of SND1 in Hep3B cells expressing a low level of
      SND1 augments, whereas stable knockdown of SND1 in QGY-7703 cells expressing a
      high level of SND1 inhibits establishment of xenografts in nude mice, indicating
      that SND1 promotes an aggressive tumorigenic phenotype. In this study we analyzed
      the role of SND1 in regulating tumor angiogenesis, a hallmark of cancer.
      Conditioned medium from Hep3B-SND1 cells stably overexpressing SND1 augmented,
      whereas that from QGY-SND1si cells stably overexpressing SND1 siRNA significantly
      inhibited angiogenesis, as analyzed by a chicken chorioallantoic membrane assay
      and a human umbilical vein endothelial cell differentiation assay. We unraveled a
      linear pathway in which SND1-induced activation of NF-kappaB resulted in
      induction of miR-221 and subsequent induction of angiogenic factors Angiogenin
      and CXCL16. Inhibition of either of these components resulted in significant
      inhibition of SND1-induced angiogenesis, thus highlighting the importance of this
      molecular cascade in regulating SND1 function. Because SND1 regulates NF-kappaB
      and miR-221, two important determinants of HCC controlling the aggressive
      phenotype, SND1 inhibition might be an effective strategy to counteract this
      fatal malady.

PMID- 22396538
TI  - Design and receptor interactions of obligate dimeric mutant of chemokine monocyte
      chemoattractant protein-1 (MCP-1).
AB  - Chemokine-receptor interactions regulate leukocyte trafficking during
      inflammation. CC chemokines exist in equilibrium between monomeric and dimeric
      forms. Although the monomers can activate chemokine receptors, dimerization is
      required for leukocyte recruitment in vivo, and it remains controversial whether
      dimeric CC chemokines can bind and activate their receptors. We have developed an
      obligate dimeric mutant of the chemokine monocyte chemoattractant protein-1 (MCP
      1) by substituting Thr(10) at the dimer interface with Cys. Biophysical analysis
      showed that MCP-1(T10C) forms a covalent dimer with similar structure to the wild
      type MCP-1 dimer. Initial cell-based assays indicated that MCP-1(T10C) could
      activate chemokine receptor CCR2 with potency reduced 1 to 2 orders of magnitude
      relative to wild type MCP-1. However, analysis of size exclusion chromatography
      fractions demonstrated that the observed activity was due to a small proportion
      of MCP-1(T10C) being monomeric and highly potent, whereas the majority dimeric
      form could neither bind nor activate CCR2 at concentrations up to 1 MUM. These
      observations help to reconcile previous conflicting results and indicate that
      dimeric CC chemokines do not bind to their receptors with affinities approaching
      those of the corresponding monomeric chemokines.

PMID- 22396540
TI  - Meiotic competent human germ cell-like cells derived from human embryonic stem
      cells induced by BMP4/WNT3A signaling and OCT4/EpCAM (epithelial cell adhesion
      molecule) selection.
AB  - The establishment of an effective germ cell selection/enrichment platform from in
      vitro differentiating human embryonic stem cells (hESCs) is crucial for studying
      the molecular and signaling processes governing human germ cell specification and
      development. In this study, we developed a germ cell-enriching system that
      enables us to identify signaling factors involved in germ cell-fate induction
      from differentiating hESCs in vitro. First, we demonstrated that selection
      through an OCT4-EGFP reporter system can successfully increase the percentage of
      meiotic-competent, germ cell-like cells from spontaneously differentiating hESCs.
      Furthermore, we showed that the pluripotency associated surface marker,
      epithelial cell adhesion molecule (EpCAM), is also expressed in human fetal
      gonads and can be used as an effective selection marker for germ cell enrichment
      from differentiating hESCs. Combining OCT4 and EpCAM selection can further enrich
      the meiotic-competent germ cell-like cell population. Also, with the percentage
      of OCT4(+)/EpCAM(+) cells as readout, we demonstrated the synergistic effect of
      BMP4/pSMAD1/5/8 and WNT3A/beta-CATENIN in promoting hESCs toward the germline
      fate. Combining BMP4/WNT3A induction and OCT4/EpCAM selection can significantly
      increase the putative germ cell population with meiotic competency. Co
      transplantation of these cells with dissociated mouse neonatal ovary cells into
      SCID mice resulted in a homogenous germ cell cluster formation in vivo. The
      stepwise platform established in this study provides a useful tool to elucidate
      the molecular mechanisms of human germ cell development, which has implications
      not only for human fertility research but regenerative medicine in general.

PMID- 22396539
TI  - Discovering protein-based inheritance through yeast genetics.

PMID- 22396541
TI  - cAMP-induced mitochondrial compartment biogenesis: role of glutathione redox
      state.
AB  - Cell fate and proliferation are tightly linked to the regulation of the
      mitochondrial energy metabolism. Hence, mitochondrial biogenesis regulation, a
      complex process that requires a tight coordination in the expression of the
      nuclear and mitochondrial genomes, has a major impact on cell fate and is of high
      importance. Here, we studied the molecular mechanisms involved in the regulation
      of mitochondrial biogenesis through a nutrient-sensing pathway, the Ras-cAMP
      pathway. Activation of this pathway induces a decrease in the cellular phosphate
      potential that alleviates the redox pressure on the mitochondrial respiratory
      chain. One of the cellular consequences of this modulation of cellular phosphate
      potential is an increase in the cellular glutathione redox state. The redox state
      of the glutathione disulfide-glutathione couple is a well known important
      indicator of the cellular redox environment, which is itself tightly linked to
      mitochondrial activity, mitochondria being the main cellular producer of reactive
      oxygen species. The master regulator of mitochondrial biogenesis in yeast (i.e.
      the transcriptional co-activator Hap4p) is positively regulated by the cellular
      glutathione redox state. Using a strain that is unable to modulate its
      glutathione redox state (Deltaglr1), we pinpoint a positive feedback loop between
      this redox state and the control of mitochondrial biogenesis. This is the first
      time that control of mitochondrial biogenesis through glutathione redox state has
      been shown.

PMID- 22396542
TI  - Goodpasture antigen-binding protein/ceramide transporter binds to human serum
      amyloid P-component and is present in brain amyloid plaques.
AB  - Serum amyloid P component (SAP) is a non-fibrillar glycoprotein belonging to the
      pentraxin family of the innate immune system. SAP is present in plasma, basement
      membranes, and amyloid deposits. This study demonstrates, for the first time,
      that the Goodpasture antigen-binding protein (GPBP) binds to human SAP. GPBP is a
      nonconventional Ser/Thr kinase for basement membrane type IV collagen. Also GPBP
      is found in plasma and in the extracellular matrix. In the present study, we
      demonstrate that GPBP specifically binds SAP in its physiological conformations,
      pentamers and decamers. The START domain in GPBP is important for this
      interaction. SAP and GPBP form complexes in blood and partly colocalize in
      amyloid plaques from Alzheimer disease patients. These data suggest the existence
      of complexes of SAP and GPBP under physiological and pathological conditions.
      These complexes are important for understanding basement membrane, blood
      physiology, and plaque formation in Alzheimer disease.

PMID- 22396543
TI  - Anticancer drugs cause release of exosomes with heat shock proteins from human
      hepatocellular carcinoma cells that elicit effective natural killer cell
      antitumor responses in vitro.
AB  - Failure of immune surveillance related to inadequate host antitumor immune
      responses has been suggested as a possible cause of the high incidence of
      recurrence and poor overall survival outcome of hepatocellular carcinoma. The
      stress-induced heat shock proteins (HSPs) are known to act as endogenous "danger
      signals" that can improve tumor immunogenicity and induce natural killer (NK)
      cell responses. Exosome is a novel secretory pathway for HSPs. In our
      experiments, the immune regulatory effect of the HSP-bearing exosomes secreted by
      human hepatocellular carcinoma cells under stress conditions on NK cells was
      studied. ELISA results showed that the production of HSP60, HSP70, and HSP90 was
      up-regulated in both cell lines in a stress-specific manner. After exposure to
      hepatocellular carcinoma cell-resistant or sensitive anticancer drugs (hereafter
      referred to as "resistant" or "sensitive" anticancer drug), the membrane
      microvesicles were actively released by hepatocellular carcinoma cells, differing
      in their ability to present HSPs on the cell surface, which were characterized as
      exosomes. Acting as a decoy, the HSP-bearing exosomes efficiently stimulated NK
      cell cytotoxicity and granzyme B production, up-regulated the expression of
      inhibitory receptor CD94, and down-regulated the expression of activating
      receptors CD69, NKG2D, and NKp44. Notably, resistant anticancer drugs enhanced
      exosome release and generated more exosome-carried HSPs, which augmented the
      activation of the cytotoxic response. In summary, our findings demonstrated that
      exosomes derived from resistant anticancer drug-treated HepG2 cells conferred
      superior immunogenicity in inducing HSP-specific NK cell responses, which
      provided a clue for finding an efficient vaccine for hepatocellular carcinoma
      immunotherapy.

PMID- 22396544
TI  - Leukotriene B4 receptor-2 promotes invasiveness and metastasis of ovarian cancer
      cells through signal transducer and activator of transcription 3 (STAT3)
      dependent up-regulation of matrix metalloproteinase 2.
AB  - Ovarian cancer is the most lethal gynecologic malignancy in women. Despite the
      fact that the metastatic spread is associated with the majority of deaths from
      ovarian cancer, the molecular mechanisms regulating the invasive and metastatic
      phenotypes of ovarian cancer are poorly understood. In this study, we
      demonstrated that BLT2, a low affinity leukotriene B(4) receptor, is highly
      expressed in OVCAR-3 and SKOV-3 human ovarian cancer cells, and that this
      receptor plays a key role in the invasiveness and metastasis of these cells
      through activation of STAT3 and consequent up-regulation of matrix
      metalloproteinase 2 (MMP2). In addition, our results suggest that activation of
      NAD(P)H oxidase-4 (NOX4) and subsequent reactive oxygen species (ROS) generation
      lie downstream of BLT2, mediating the stimulation of STAT3-MMP2 cascade in this
      process. For example, knockdown of BLT2 or NOX4 using each specific siRNA
      suppressed STAT3 stimulation and MMP2 expression. Similarly, inhibition of STAT3
      suppressed the expression of MMP2, thus leading to attenuated invasiveness of
      these ovarian cancer cells. Finally, the metastasis of SKOV-3 cells in nude mice
      was markedly suppressed by pharmacological inhibition of BLT2. Together, our
      results implicate a BLT2-NOX4-ROS-STAT3-MMP2 cascade in the invasiveness and
      metastasis of ovarian cancer cells.

PMID- 22396545
TI  - Tumor-suppressing function of caspase-2 requires catalytic site Cys-320 and site
      Ser-139 in mice.
AB  - The multifunctional caspase-2 protein is involved in apoptosis, NF-kappaB
      regulation, and tumor suppression in mice. However, the mechanisms of caspase-2
      responsible for tumor suppression remain unclear. Here we identified two sites of
      caspase-2, the catalytic Cys-320 site and the Ser-139 site, to be important for
      suppression of cellular transformation and tumorigenesis. Using SV40- and K-Ras
      transformed caspase-2 KO mouse embryonic fibroblast cells reconstituted with
      expression of wild-type, catalytic dead (C320A), or Ser-139 (S139A) mutant
      caspase-2, we demonstrated that similar to caspase-2 deficiency, when Cys-320 and
      Ser-139 were mutated, caspase-2 lost its ability to inhibit cellular
      transformation and tumorigenesis. These mutant cells exhibited enhanced cell
      proliferation, elevated clonogenic activity, accelerated anchorage-independent
      growth, and transformation and were highly tumorigenic, rapidly producing large
      tumors in athymic nude mice. Investigation into the underlying mechanism showed
      that these two residues are needed for caspase-2 to suppress NF-kappaB activity,
      promote apoptosis, and sustain the G(2)/M checkpoint following DNA damage
      induction. In addition, tumors in nude mice derived from the two mutant cell
      lines had higher constitutive NF-kappaB activity and elevated expression of NF
      kappaB targets of antiapoptotic proteins Bcl-xL, XIAP, and cIAP2. A reduction in
      caspase-2 mRNA was associated with multiple types of cancers in patients.
      Together, these observations suggest the combined functions of caspase-2 in
      suppressing NF-kappaB activation, promoting apoptosis, and sustaining G(2)/M
      checkpoint contribute to caspase-2 tumor-suppressing function and that caspase-2
      may also impact tumor suppression in humans. These findings provide insight into
      tumor suppression at the cross-roads of apoptosis, cell cycle checkpoint, and NF
      kappaB pathways.

PMID- 22396546
TI  - Influenza A virus neuraminidase protein enhances cell survival through
      interaction with carcinoembryonic antigen-related cell adhesion molecule 6
      (CEACAM6) protein.
AB  - The influenza virus neuraminidase (NA) protein primarily aids in the release of
      progeny virions from infected cells. Here, we demonstrate a novel role for NA in
      enhancing host cell survival by activating the Src/Akt signaling axis via an
      interaction with carcinoembryonic antigen-related cell adhesion molecule
      6/cluster of differentiation 66c (C6). NA/C6 interaction leads to increased
      tyrosyl phosphorylation of Src, FAK, Akt, GSK3beta, and Bcl-2, which affects cell
      survival, proliferation, migration, differentiation, and apoptosis. siRNA
      mediated suppression of C6 resulted in a down-regulation of activated Src, FAK,
      and Akt, increased apoptosis, and reduced expression of viral proteins and viral
      titers in influenza virus-infected human lung adenocarcinoma epithelial and
      normal human bronchial epithelial cells. These findings indicate that influenza
      NA not only aids in the release of progeny virions, but also cell survival during
      viral replication.

PMID- 22396547
TI  - Interplay between minor and major groove-binding transcription factors Sox2 and
      Oct1 in translocation on DNA studied by paramagnetic and diamagnetic NMR.
AB  - The pathways whereby Sox2 scans DNA to locate its specific binding site are
      investigated by NMR in specific and nonspecific Sox2.DNA complexes and in a
      specific ternary complex with Oct1 on the Hoxb1 regulatory element. Direct
      transfer of Sox2 between nonspecific sites on different DNA molecules occurs
      without dissociation into free solution at a rate of ~10(6) M(-1) s(-1), whereas
      one-dimensional sliding proceeds with a diffusion constant of >=0.1 MUm(2).s(-1).
      Translocation of Sox2 from one specific DNA site to another occurs via jumping,
      involving complete dissociation into free solution (k(d) ~5-6 s(-1)) followed by
      reassociation (k(a) ~5 * 10(8) M(-1) s(-1)). In the presence of Oct1 bound to an
      adjacent specific site, k(d) is reduced by more than 10-fold. Paramagnetic
      relaxation measurements, however, demonstrate that sparsely populated (<1%),
      transient states involving nonspecifically bound Sox2 in rapid exchange with
      specifically bound Sox2 are sampled in both binary Sox2.DNA- and ternary
      Oct1.Sox2.Hoxb1-DNA-specific complexes. Moreover, Sox2 modulates the mechanism of
      translocation of Oct1. Both Sox2 and the Oct1 POU(HD) domain are transiently
      released from the specific ternary complex by sliding to an adjacent nonspecific
      site, followed by direct transfer to another DNA molecule, whereas the Oct1
      POU(S) domain is fixed to its specific site through direct interactions with
      Sox2. Intermolecular translocation of POU(HD) results in the formation of a
      bridged intermediate spanning two DNA molecules, enhancing the probability of
      complete intermolecular translocation of Oct1. By way of contrast, in the
      specific Oct1.DNA binary complex, POU(S) undergoes direct intermolecular
      translocation, whereas POU(HD) scans the DNA by sliding.

PMID- 22396548
TI  - Intestinal expression of mouse Abcg2/breast cancer resistance protein (BCRP) gene
      is under control of circadian clock-activating transcription factor-4 pathway.
AB  - ABCG2, encoding breast cancer resistance protein (BCRP), is a member of the ATP
      binding cassette transporter family and is often associated with cancer
      chemotherapeutic resistance. BCRP is also expressed in a variety of normal cells
      and acts as a xenobiotic efflux transporter. Because intestinal BCRP limits
      systemic exposure to xenobiotics, alterations in the function and expression of
      this transporter could account for part of the variation in oral drug absorption.
      In this study, we show that ATF4, a molecular component of the circadian clock,
      induces circadian expression of the Abcg2 gene in mouse small intestine. Three
      types of leader exons (termed exons 1A, 1B, and 1C) are identified in the 5'
      untranslated region of mouse Abcg2 transcripts. The exon 1B-containing Abcg2
      transcript was the only isoform detected in mouse small intestine, and its mRNA
      levels oscillated in a circadian time-dependent manner. ATF4 bound time
      dependently to the cAMP response element within the exon 1B promoter region of
      the Abcg2 gene, thereby causing the oscillation of BCRP protein abundance and its
      efflux pump function. The circadian clock-ATF4 pathway appears to enhance the
      function of BCRP during a specific time window and to modulate intestinal drug
      absorption. Our findings suggest a mechanism underlying circadian change in
      xenobiotic detoxification.

PMID- 22396550
TI  - Hypercapnia induces cleavage and nuclear localization of RelB protein, giving
      insight into CO2 sensing and signaling.
AB  - Carbon dioxide (CO(2)) is increasingly being appreciated as an intracellular
      signaling molecule that affects inflammatory and immune responses. Elevated
      arterial CO(2) (hypercapnia) is encountered in a range of clinical conditions,
      including chronic obstructive pulmonary disease, and as a consequence of
      therapeutic ventilation in acute respiratory distress syndrome. In patients
      suffering from this syndrome, therapeutic hypoventilation strategy designed to
      reduce mechanical damage to the lungs is accompanied by systemic hypercapnia and
      associated acidosis, which are associated with improved patient outcome. However,
      the molecular mechanisms underlying the beneficial effects of hypercapnia and the
      relative contribution of elevated CO(2) or associated acidosis to this response
      remain poorly understood. Recently, a role for the non-canonical NF-kappaB
      pathway has been postulated to be important in signaling the cellular
      transcriptional response to CO(2). In this study, we demonstrate that in cells
      exposed to elevated CO(2), the NF-kappaB family member RelB was cleaved to a
      lower molecular weight form and translocated to the nucleus in both mouse
      embryonic fibroblasts and human pulmonary epithelial cells (A549). Furthermore,
      elevated nuclear RelB was observed in vivo and correlated with hypercapnia
      induced protection against LPS-induced lung injury. Hypercapnia-induced RelB
      processing was sensitive to proteasomal inhibition by MG-132 but was independent
      of the activity of glycogen synthase kinase 3beta or MALT-1, both of which have
      been previously shown to mediate RelB processing. Taken together, these data
      demonstrate that RelB is a CO(2)-sensitive NF-kappaB family member that may
      contribute to the beneficial effects of hypercapnia in inflammatory diseases of
      the lung.

PMID- 22396549
TI  - Disruption of proprotein convertase 1/3 (PC1/3) expression in mice causes innate
      immune defects and uncontrolled cytokine secretion.
AB  - The proprotein convertase 1/3 is expressed in the regulated secretory pathway of
      neural and endocrine cells. Its major function is in the post-translational
      processing and activation of precursor proteins. The PC1/3 knock-out (KO) mouse
      model has allowed us to elucidate its physiological functions in studies focused
      primarily on neuroendocrine tissues. However, PC1/3 is also expressed in cells of
      the immune system, mainly in macrophages. The present study explores the effects
      of innate immune challenge in the PC1/3 KO mouse. PC1/3 KO mice have an enlarged
      spleen with marked disorganization of the marginal zone and red pulp.
      Immunohistochemical studies using various markers demonstrate a depletion of
      dendritic cells in PC1/3 KO spleens. When challenged with lipopolysaccharide,
      PC1/3 KO mice are more susceptible to septic shock than wild-type controls or
      other PC KO mice, such as PC2 and PC7 null mice. Plasma levels of proinflammatory
      cytokines (IL-6, IL-1beta, and TNF-alpha) were very significantly elevated in
      PC1/3 KO mice, consistent with a hypercytokinemia, i.e. indicative of a major
      systemic uncontrolled inflammatory response or cytokine storm. Peritoneal
      macrophages isolated from PC1/3 KO mice also demonstrate elevated cytokine
      secretion when treated with LPS. Electron micrographs show morphological features
      indicating a prolonged activation of these cells following LPS stimulation. We
      also present evidence that the proinflammatory T(h)1 pathway is dominant in the
      PC1/3 KO mouse model. We conclude that aside from its important role in
      neuroendocrine functions PC1/3 also has an important role in the regulation of
      the innate immune system, most likely through the regulation of cytokine
      secretion in macrophages.

PMID- 22396552
TI  - Expression of claudins 7 and 18 in pancreatic ductal adenocarcinoma: association
      with features of differentiation.
AB  - AIM: This study was undertaken to evaluate the expression of claudins 7 and 18 in
      pancreatic ductal adenocarcinoma. METHODS AND RESULTS: Material tested included
      111 operated samples and 47 additional biopsy samples consisting of 26 cases of
      pancreatitis, 3 cases of pancreatic intraepithelial neoplasia and 18 ductal
      adenocarcinomas. Samples were stained with antibodies to claudins 7 and 18 and
      analysed for membranous and cytoplasmic expression. Membrane bound claudin 7 and
      18 expression was detected in 62 of 105 (59%) and 78 of 111 (70%) cases,
      respectively. Membrane bound claudin 7 and 18 were associated with large or
      intermediate neoplastic ducts (p=0.01, p=0.002, respectively). Well
      differentiated pancreatic adenocarcinomas displayed more cases with membrane
      bound claudin 7 or 18 immunopositivity (p=0.003, p=0.03, respectively). All
      pancreatic intraepithelial neoplasias studied expressed membrane bound claudin
      18. Membrane bound claudin 7 or 18 positivity was not associated with survival
      (p=0.17, p=0.98). In the biopsy cases membrane bound claudin 18 had 100%
      specificity and 51% sensitivity for a tumour marker. CONCLUSION: Claudin 7 and 18
      expression is related to gland size of neoplastic cells and is especially found
      in tumours with intermediate and large ducts and well differentiated tumours.
      Membrane bound claudin 18, when present, is a useful marker for diagnosis of
      pancreatic cancer. Claudins 7 and 18 were not associated with patient survival or
      spread of tumours.

PMID- 22396551
TI  - Macin family of antimicrobial proteins combines antimicrobial and nerve repair
      activities.
AB  - The tertiary structures of theromacin and neuromacin confirmed the macin protein
      family as a self-contained family of antimicrobial proteins within the
      superfamily of scorpion toxin-like proteins. The macins, which also comprise
      hydramacin-1, are antimicrobially active against Gram-positive and Gram-negative
      bacteria. Despite high sequence identity, the three proteins showed distinct
      differences with respect to their biological activity. Neuromacin exhibited a
      significantly stronger capacity to permeabilize the cytoplasmic membrane of
      Bacillus megaterium than theromacin and hydramacin-1. Accordingly, it is the only
      macin that displays pore-forming activity and that was potently active against
      Staphylococcus aureus. Moreover, neuromacin and hydramacin-1 led to an
      aggregation of bacterial cells that was not observed with theromacin. Analysis of
      the molecular surface properties of macins allowed confirmation of the barnacle
      model as the mechanistic model for the aggregation effect. Besides being
      antimicrobially active, neuromacin and theromacin, in contrast to hydramacin-1,
      were able to enhance the repair of leech nerves ex vivo. Notably, all three
      macins enhanced the viability of murine neuroblastoma cells, extending their
      functional characteristics. As neuromacin appears to be both a functional and
      structural chimera of hydramacin-1 and theromacin, the putative structural
      correlate responsible for the nerve repair capacity in leech was located to a
      cluster of six amino acid residues using the sequence similarity of surface
      exposed regions.

PMID- 22396553
TI  - Refractory asthma: lessons learned from the bronchoscope.

PMID- 22396554
TI  - Surveillance cultures in respiratory tract infections: are they useful?

PMID- 22396555
TI  - Just do it!: meeting patient safety goals in VTE prevention.

PMID- 22396556
TI  - Obstructive sleep apnea: the elephant in the cardiovascular room.

PMID- 22396557
TI  - The lung cancer stage page: there when you need it--staginglungcancer.org.

PMID- 22396558
TI  - Point: are limited resections appropriate in non-small cell lung cancer? Yes.

PMID- 22396559
TI  - Counterpoint: are limited resections appropriate in non-small cell lung cancer?
      No: don't overdo it, and don't get confused.

PMID- 22396560
TI  - Mine is bigger than yours: measures of effect size in research.
AB  - Results of studies that use laboratory tests are often easy to interpret, because
      we are familiar with the units and how to interpret them. However, this is not
      the case when the results are presented as ORs, relative risks, correlation, or
      scores on an unfamiliar scale. This article explains these various indices of
      effect sizes-how they are calculated, what they mean, and how they are
      interpreted.

PMID- 22396562
TI  - Frontiers in occupational and environmental lung disease research.
AB  - Two central challenges in the field of occupational and environmental
      epidemiology include accurately measuring biologic responses to exposure and
      preventing subsequent disease. As exposure-related lung diseases continue to be
      identified, advances in exposure biology have introduced toxicogenomic approaches
      that detect biomarkers of exposure at the gene, protein, and metabolite levels.
      Moreover, genetic epidemiology research has focused more recently on common, low
      penetrant (ie, low-relative-risk) genetic variants that may interact with
      commonly encountered exposures. A number of such gene by environment interactions
      have been identified for airways and interstitial lung diseases, with the goal of
      preventing disease among susceptible populations that may not otherwise have been
      identified. Exhaled breath condensate analysis has provided another noninvasive
      means of assessing toxicant exposures and systemic effects. As these technologies
      become more refined, clinicians and public health practitioners will need to
      appreciate the social implications of the individual- and population-level risks
      conferred by certain genetic polymorphisms or by biomarker evidence of exposure.
      At present, the primary approach to occupational and environmental lung disease
      prevention remains elimination or reduction of known hazardous exposures and
      requires continued application of local and international resources toward
      exposure control.

PMID- 22396561
TI  - Ubiquitination and proteolysis in acute lung injury.
AB  - Ubiquitination is a posttranslational modification that regulates a variety of
      cellular functions depending on timing, subcellular localization, and type of
      tagging, as well as modulators of ubiquitin binding leading to proteasomal or
      lysosomal degradation or nonproteolytic modifications. Ubiquitination plays an
      important role in the pathogenesis of acute lung injury (ALI) and other lung
      diseases with pathologies secondary to inflammation, mechanical ventilation, and
      decreased physical mobility. Particularly, ubiquitination has been shown to
      affect alveolar epithelial barrier function and alveolar edema clearance by
      targeting the Na,K-ATPase and epithelial Na(+) channels upon lung injury.
      Notably, the proteasomal system also exhibits distinct functions in the
      extracellular space, which may contribute to the pathogenesis of ALI and other
      pulmonary diseases. Better understanding of these mechanisms may ultimately lead
      to novel therapeutic modalities by targeting elements of the ubiquitination
      pathway.

PMID- 22396563
TI  - Reframing the influence of the Health Insurance Portability and Accountability
      Act on research.
AB  - The purpose of this article is to review the Health Insurance Portability and
      Accountability Act (HIPAA), the Privacy Rule, the Security Rule, and common
      issues encountered by researchers related to these federal privacy and security
      requirements. This article discusses the misconceptions that researchers may hold
      about HIPAA, including the process for reviewing protected health information
      when preparing to conduct a study, potential constraint on participant
      recruitment, and application of HIPAA to a researcher's clinical population. We
      also present ways to reframe the negative connotations associated with this
      regulation and provide tips for researchers about how to work with HIPAA when
      planning and conducting a study and reporting on study findings. Finally, we
      suggest that the principles of HIPAA be considered when conducting studies in
      international settings.

PMID- 22396565
TI  - Neurogenic pulmonary edema: successful treatment with IV phentolamine.
AB  - Neurogenic pulmonary edema (NPE) is a clinical syndrome characterized by the
      acute onset of pulmonary edema following a significant CNS insult. The cause is
      believed to be a surge of catecholamines that results in cardiopulmonary
      dysfunction. Although there are myriad case reports describing CNS events that
      are associated with this syndrome, few studies have identified specific treatment
      modalities. We present a case of NPE caused by an intracranial hemorrhage from a
      ruptured arteriovenous malformation. We uniquely document a rise and fall of
      serum catecholamine levels correlating with disease activity and a dramatic
      clinical response to IV phentolamine.

PMID- 22396564
TI  - Physician reimbursement for critical care services integrating palliative care
      for patients who are critically ill.
AB  - Patients with advanced illness often spend time in an ICU, while nearly one-third
      of patients with advanced cancer who receive Medicare die in hospitals, often
      with failed ICU care. For most, death occurs following the withdrawal or
      withholding of life-sustaining treatments. The integration of palliative care is
      essential for high-quality critical care. Although palliative care specialists
      are becoming increasingly available, intensivists and other physicians are also
      expected to provide basic palliative care, including symptom treatment and
      communication about goals of care. Patients who are critically ill are often
      unable to make decisions about their care. In these situations, physicians must
      meet with family members or other surrogates to determine appropriate medical
      treatments. These meetings require clinical expertise to ensure that patient
      values are explored for medical decision making about therapeutic options,
      including palliative care. Meetings with families take time. Issues related to
      the disease process, prognosis, and treatment plan are complex, and decisions
      about the use or limitation of intensive care therapies have life-or-death
      implications. Inadequate reimbursement for physician services may be a barrier to
      the optimal delivery of high-quality palliative care, including effective
      communication. Appropriate documentation of time spent integrating palliative and
      critical care for patients who are critically ill can be consistent with the
      Current Procedural Terminology codes (99291 and 99292) for critical care
      services. The purpose of this article is to help intensivists and other providers
      understand the circumstances in which integration of palliative and critical care
      meets the definition of critical care services for billing purposes.

PMID- 22396566
TI  - Interstitial pneumonia associated with bullous pemphigoid.
AB  - Bullous pemphigoid, the most common autoimmune blistering disease, is
      characterized by an autoimmune response to a component of hemidesmosomes within
      the dermal-epidermal junction. Immunofluorescence examination of skin biopsies
      demonstrates linear deposition of IgG and C3 in the basement membrane zone. A 73
      year-old woman was admitted to our institution because of interstitial lung
      disease with persistent dry cough, dyspnea on exertion, and bullous eruptions on
      the skin of her trunk and extremities. Chest CT scan, BAL fluid, and
      transbronchial lung biopsy findings indicated a likely nonspecific interstitial
      pneumonia pattern. Direct immunofluorescence showed linear deposition of IgG and
      C3 along the basement membranes of the lung and skin specimens. Lung disorders
      associated with bullous pemphigoid are extremely rare, and, to our knowledge,
      this is the first report of an immunologically confirmed case of interstitial
      pneumonia.

PMID- 22396568
TI  - An elderly woman with stridor.

PMID- 22396567
TI  - Acute cardiopulmonary failure from sleep-disordered breathing.
AB  - Sleep-disordered breathing (SDB) comprises a diverse set of disorders marked by
      abnormal respiration during sleep. Clinicians should realize that SDB may present
      as acute cardiopulmonary failure in susceptible patients. In this review, we
      discuss three clinical phenotypes of acute cardiopulmonary failure from SDB:
      acute ventilatory failure, acute congestive heart failure, and sudden death. We
      review the pathophysiologic mechanisms and recommend general principles for
      management. Timely recognition of, and therapy for, SDB in the setting of acute
      cardiopulmonary failure may improve short- and long-term outcomes.

PMID- 22396569
TI  - A 63-year-old woman with recurrent fever and productive cough.

PMID- 22396570
TI  - An 81-year-old man with cutaneous periumbilical purpura.

PMID- 22396571
TI  - Bronchiectasis: defining specific treatment needs.

PMID- 22396572
TI  - Increased number of pulmonary embolisms in sarcoidosis patients.

PMID- 22396573
TI  - Bedside ultrasonography for evaluation of pneumothorax.

PMID- 22396574
TI  - Increased adverse events after percutaneous coronary intervention in patients
      with COPD.

PMID- 22396575
TI  - Fluid shift in obstructive sleep apnea: does it really have no role in the
      pathogenesis?

PMID- 22396576
TI  - Prognosis of patients with silicosis due to denim sandblasting.

PMID- 22396577
TI  - Lung function data interpretation.

PMID- 22396578
TI  - The diagnosis of extranodal marginal zone B-cell lymphoma of mucosa-associated
      lymphoid tissue.

PMID- 22396579
TI  - IV delivery of fluorescent beads.

PMID- 22396580
TI  - Hemophagocytic lymphohistiocytosis mimicking septic shock.

PMID- 22396581
TI  - Platelet function measurement-based strategy to reduce bleeding and waiting time
      in clopidogrel-treated patients undergoing coronary artery bypass graft surgery:
      the timing based on platelet function strategy to reduce clopidogrel-associated
      bleeding related to CABG (TARGET-CABG) study.
AB  - BACKGROUND: Aspirin and clopidogrel therapy is associated with a variable
      bleeding risk in patients undergoing coronary artery bypass graft surgery (CABG).
      We evaluated the role of platelet function testing in clopidogrel-treated
      patients undergoing CABG. METHODS AND RESULTS: One hundred eighty patients on
      background aspirin with/without clopidogrel therapy undergoing elective first
      time isolated on-pump CABG were enrolled in a prospective single-center,
      nonrandomized, unblinded investigation (Timing Based on Platelet Function
      Strategy to Reduce Clopidogrel-Associated Bleeding Related to CABG [TARGET-CABG]
      study) between September 2008 and January 2011. Clopidogrel responsiveness (ADP
      induced platelet-fibrin clot strength [MA(ADP)]) was determined by
      thrombelastography; CABG was done within 1 day, 3-5 days, and >5 days in patients
      with an MA(ADP) >50 mm, 35-50 mm, and <35 mm, respectively. The primary end point
      was 24-hour chest tube drainage and key secondary end point was total number of
      transfused red blood cells. Equivalence was defined as <=25% difference between
      groups. ANCOVA was used to adjust for confounders. Mean 24-hour chest tube
      drainage in clopidogrel-treated patients was 93% (95% confidence interval, 81
      107%) of the amount observed in clopidogrel-naive patients, and the total amount
      of red blood cells transfused did not differ between groups (1.80 U versus 2.08
      U, respectively, P=0.540). The total waiting period in clopidogrel-treated
      patients was 233 days (mean, 2.7 days per patient). CONCLUSIONS: A strategy based
      on preoperative platelet function testing to determine the timing of CABG in
      clopidogrel-treated patients was associated with the same amount of bleeding
      observed in clopidogrel-naive patients and ~50% shorter waiting time than
      recommended in the current guidelines. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00857155.

PMID- 22396583
TI  - Comparison of 5-year clinical outcomes between sirolimus-versus paclitaxel
      eluting stent: Korean multicenter network analysis of 9000-patient cohort.
AB  - BACKGROUND: The paclitaxel-eluting stent (PES) and sirolimus-eluting stent (SES)
      are first-generation drug-eluting stents (DES) that have been the most widely
      used; however, it is unclear whether there are differences in the long-term
      safety and efficacy between the 2 stents. The long-term effectiveness of DES in
      unselected people with diabetes is also currently unclear. Moreover, the
      possibility of late catch-up is suggested in the DES population. METHODS AND
      RESULTS: This study is an 8-center collaborative network analysis of all comers
      who received SES and PES. All patients who received SES and PES from February
      2003 to October 2006 were enrolled. We analyzed 9315 patients (33.3% with
      diabetes) treated with SES or PES in the major 8 centers representing whole area
      of Korea. The primary end point was a major adverse cardiac event (MACE)
      composite of overall death, myocardial infarction, and target lesion
      revascularization. All analyses were performed using multivariable, adjusted
      models and propensity score-matching methods. Long-term MACE for 5 years were
      significantly lower in the SES than the PES group (13.3% versus 15.6%; hazard
      ratio, 0.82; 95% confidence interval, 0.71 to 0.96; P=0.01), which was mainly
      driven by the difference of MACE within the first year (hazard ratio, 0.73; 95%
      CI, 0.59 to 0.90; P=0.003), but the rate of MACE between 1 and 5 years in the
      landmark analysis was not different between the 2 stents (1.9 versus 2.0%/yr). In
      the subpopulation of people with diabetes, in contrast to the whole population,
      PES was comparable to SES in terms of any clinical outcome, both within the first
      year and from 1 to 5 years (MACE for 5 years, 20.3 versus 17.9%; MACE within the
      first year, 9.6 versus 8.2%; MACE 1 to 5 years, 2.9 versus 2.6%/yr). CONCLUSIONS:
      The PES was inferior to the SES in the clinical follow-up of more than 9000
      patients' cohort for 5 years, which was mainly driven by the difference in the
      first year. In the subpopulation of people with diabetes that showed higher MACE
      than people without diabetes, however, PES was comparable to SES in any clinical
      outcome for 5 years. Although these 2 stents are not frequently used as before,
      the data would be useful to expect the long-term clinical course of the current
      DES.

PMID- 22396584
TI  - Early detection of an underperforming implantable cardiovascular device using an
      automated safety surveillance tool.
AB  - BACKGROUND: Postmarket medical device surveillance in the United States depends
      largely on voluntary reporting of adverse events. Consequently, early safety
      signals may be missed, exposing patients to potentially hazardous products. The
      aim of this study was to assess the feasibility of using an automated safety
      surveillance tool to detect early signals that a marketed implantable cardiac
      device was underperforming. METHODS AND RESULTS: For this purpose, we performed
      simulated prospective monthly full-cohort and propensity-matched comparative
      survival analyses on our 3-center database of Sprint Fidelis and Quattro Secure
      implantable cardioverter-defibrillator leads, using a commercially available
      automated surveillance tool that was preset to trigger an alert if the log rank
      probability value was <0.05. During the study, 84 of 1035 Fidelis (8.1%) and 23
      of 1675 Quattro (1.4%) leads failed. The simulated full-cohort analysis triggered
      a sustained alert for Fidelis leads beginning 13 months after the first implant
      and 2 years before Fidelis leads were removed from the market. Of the 1035
      patients who had Fidelis leads, up to 969 (93.6%) were successfully matched to
      Quattro patients. In the propensity-matched analysis, the alert triggered 22
      months after the first Fidelis implant and more than 1 year before the lead was
      recalled. CONCLUSIONS: An active automated safety surveillance system could have
      identified this implantable cardiovascular device problem substantially sooner
      than was achieved through existing postmarket surveillance methods. Such a tool,
      when applied to clinical registries and remote monitoring databases, may limit
      the exposure of large populations to underperforming and potentially hazardous
      cardiovascular devices.

PMID- 22396582
TI  - Incidence and outcome of surgical procedures after coronary bare-metal and drug
      eluting stent implantation: a report from the CREDO-Kyoto PCI/CABG registry
      cohort-2.
AB  - BACKGROUND: There still remain safety concerns on surgical procedures after
      coronary drug-eluting stents (DES) implantation, and optimal management of
      perioperative antiplatelet therapy (APT) has not been yet established. METHODS
      AND RESULTS: During 3-year follow-up of 12 207 patients (DES=6802 patients and
      bare-metal stent [BMS] only=5405 patients) who underwent coronary stent
      implantation in the CREDO-Kyoto registry cohort-2, surgical procedures were
      performed in 2398 patients (DES=1295 patients and BMS=1103 patients). Surgical
      procedures (early surgery in particular) were more frequently performed in the
      BMS group than in the DES group (4.4% versus 1.9% at 42-day and 23% versus 21% at
      3-year, log-rank P=0.0007). Cumulative incidences of death/myocardial infarction
      (MI)/stent thrombosis (ST) and bleeding at 30 days after surgery were low,
      without differences between BMS and DES (3.5% versus 2.9%, P=0.4 and 3.2% versus
      2.1%, P=0.2, respectively). The adjusted risks of DES use relative to BMS use for
      death/MI/ST and bleeding were not significant (hazard ratio: 1.63, 95% confidence
      interval: 0.93 to 2.87, P=0.09 and hazard ratio: 0.6, 95% confidence interval:
      0.34 to 1.06, P=0.08, respectively). The risks of perioperative single- and no
      APT relative to dual-APT for both death/MI/ST and bleeding were not significant;
      single-APT as compared with dual-APT tended to be associated with lower risk for
      death/MI/ST (hazard ratio: 0.4, 95% confidence interval: 0.13 to 1.01, P=0.053).
      CONCLUSIONS: Surgical procedures were commonly performed after coronary stent
      implantation, and the risk of ischemic and bleeding complications in surgical
      procedures was low. In patients selected to receive DES or BMS, there were no
      differences in outcomes. Perioperative administration of dual-APT was not
      associated with lower risk for ischemic events.

PMID- 22396585
TI  - Long-term effects of incident diabetes mellitus on cardiovascular outcomes in
      people treated for hypertension: the ALLHAT Diabetes Extension Study.
AB  - BACKGROUND: Thiazide-type diuretics are associated with an increased incidence of
      diabetes compared with other antihypertensive medications. In this study, we
      determined the long-term cardiovascular disease (CVD) consequences of incident
      diuretic-associated diabetes compared with the effects of incident diabetes
      associated with calcium channel blocker and angiotensin-converting enzyme
      inhibitor use. METHODS AND RESULTS: A total of 22 418 participants from the
      ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack
      Trial) with baseline diabetes, incident diabetes (7.5% with chlorthalidone, 5.6%
      with amlodipine, and 4.3% with lisinopril), or no diabetes at 2 years of in-trial
      follow-up were followed for a mean total of 6.9 years (2.9 years in-trial and 4
      additional years posttrial) through the use of national databases. The primary
      outcome was CVD mortality (death from coronary heart disease [CHD], stroke, heart
      failure, or other CVD). Among other outcomes were all-cause mortality, non-CVD
      mortality, and CHD (nonfatal myocardial infarction or fatal CHD). Participants on
      chlorthalidone with incident diabetes versus no diabetes had consistently lower,
      nonsignificant risk for CVD mortality (hazard ratio [HR], 1.04; 95% CI, 0.74
      1.47), all-cause mortality (HR, 1.04; 95% CI, 0.82-1.30), and non-CVD mortality
      (HR, 1.05; 95% CI, 0.77-1.42) than participants on amlodipine or lisinopril with
      incident diabetes (HR range, 1.22-1.53). Participants with incident diabetes had
      elevated CHD risk compared with those with no diabetes (HR, 1.46; 95% CI, 1.09
      1.96), but those on chlorthalidone had significantly lower risk than those on
      lisinopril (HR, 1.18 versus 2.57; P=0.04 for interaction). CONCLUSIONS: The
      findings suggest that thiazide-related incident diabetes has less adverse long
      term CVD impact than incident diabetes that develops while on other
      antihypertensive medications.

PMID- 22396586
TI  - Addition of frailty and disability to cardiac surgery risk scores identifies
      elderly patients at high risk of mortality or major morbidity.
AB  - Background- Cardiac surgery risk scores perform poorly in elderly patients, in
      part because they do not take into account frailty and disability which are
      critical determinants of health status with advanced age. There is an unmet need
      to combine established cardiac surgery risk scores with measures of frailty and
      disability to provide a more complete model for risk prediction in elderly
      patients undergoing cardiac surgery.  Methods and Results- This was a
      prospective, multicenter cohort study of elderly patients (>=70 years) undergoing
      coronary artery bypass and/or valve surgery in the United States and Canada. Four
      different frailty scales, 3 disability scales, and 5 cardiac surgery risk scores
      were measured in all patients. The primary outcome was the STS composite end
      point of in-hospital postoperative mortality or major morbidity. A total of 152
      patients were enrolled, with a mean age of 75.9+/-4.4 years and 34% women.
      Depending on the scale used, 20-46% of patients were found to be frail, and 5-76%
      were found to have at least 1 disability. The most predictive scale in each
      domain was: 5-meter gait speed >=6 seconds as a measure of frailty (odds ratio
      [OR], 2.63; 95% confidence interval [CI], 1.17-5.90), >=3 impairments in the Nagi
      scale as a measure of disability (OR, 2.98; 95% CI, 1.35-6.56) and either the
      Parsonnet score (OR, 1.08; 95% CI, 1.04-1.13) or Society of Thoracic Surgeons
      Predicted Risk of Mortality or Major Morbidity (STS-PROMM) (OR, 1.05; 95% CI,
      1.01-1.09) as a cardiac surgery risk score. Compared with the Parsonnet score or
      STS-PROMM alone, (area under the curve, 0.68-0.72), addition of frailty and
      disability provided incremental value and improved model discrimination (area
      under the curve, 0.73-0.76).  Conclusions- Clinicians should use an integrative
      approach combining frailty, disability, and risk scores to better characterize
      elderly patients referred for cardiac surgery and identify those that are at
      increased risk.

PMID- 22396587
TI  - Coronary artery bypass graft: contemporary heart surgery center performance in
      China.
AB  - BACKGROUND: The use of coronary artery bypass grafting (CABG) surgery in China is
      growing, but little is known about hospital-level performance. We sought to
      characterize the variation in performance across hospitals participating in a
      national registry in China. METHODS AND RESULTS: The study sample was drawn from
      the Chinese Cardiac Surgery Registry, a national multicenter database that
      includes 43 hospitals across 13 provinces and 4 direct-controlled municipalities
      in China. We assessed consecutive patients undergoing isolated CABG surgery
      during the period of January 1, 2007, through December 31, 2008. Hierarchical
      generalized linear models were used to estimate hospital-level risk-standardized
      in-hospital all-cause mortality rates (RSMR) and major complication rates
      (RSMCR), which included death, myocardial infarction, reoperation for bleeding,
      mediastinal infection, stroke, reintubation, and renal failure. Among 8739
      patients who underwent isolated CABG surgery, the mean age was 62.2 years
      (SD=9.2), and 78% were male. Observed in-hospital mortality and complication
      rates were 2.2% (95% confidence interval [CI], 1.9-2.5%) and 6.6% (95% CI, 6.1
      7.1%), respectively. The mean RSMR was 1.9% (SD=1.1), with a range of 0.7-5.8%,
      and the mean RSMCR was 6.4% (SD=1.5), with a range of 3.8-10.1%. The odds of
      dying and the odds of having a complication after CABG surgery at a hospital 1 SD
      below the average relative to a hospital 1 SD above the average were 2.06 (95%
      CI, 1.40-3.04) and 1.53 (95% CI, 1.31-1.79), respectively. The Eastern region had
      the lowest RSMR and RSMCR (1.6% and 5.8%, respectively), whereas the Central
      region had the highest RSMR (2.5%) and the Southern region had the highest RSMCR
      (7.7%). CONCLUSIONS: Mortality and complication rates after CABG surgery in the
      Chinese Cardiac Surgery Registry are generally low but vary by hospital and
      region within China. These results suggest that there are opportunities to
      improve outcomes in some CABG facilities.

PMID- 22396588
TI  - Versatile pathway-centric approach based on high-throughput sequencing to
      anticancer drug discovery.
AB  - The advent of powerful genomics technologies has uncovered many fundamental
      aspects of biology, including the mechanisms of cancer; however, it has not been
      appropriately matched by the development of global approaches to discover new
      medicines against human diseases. Here we describe a unique high-throughput
      screening strategy by high-throughput sequencing, referred to as HTS(2), to meet
      this challenge. This technology enables large-scale and quantitative analysis of
      gene matrices associated with specific disease phenotypes, therefore allowing
      screening for small molecules that can specifically intervene with disease-linked
      gene-expression events. By initially applying this multitarget strategy to the
      pressing problem of hormone-refractory prostate cancer, which tends to be
      accelerated by the current antiandrogen therapy, we identify Peruvoside, a
      cardiac glycoside, which can potently inhibit both androgen-sensitive and 
      resistant prostate cancer cells without triggering severe cytotoxicity. We
      further show that, despite transcriptional reprogramming in prostate cancer cells
      at different disease stages, the compound can effectively block androgen receptor
      dependent gene expression by inducing rapid androgen receptor degradation via the
      proteasome pathway. These findings establish a genomics-based phenotypic
      screening approach capable of quickly connecting pathways of phenotypic response
      to the molecular mechanism of drug action, thus offering a unique pathway-centric
      strategy for drug discovery.

PMID- 22396589
TI  - Antiproliferative small-molecule inhibitors of transcription factor LSF reveal
      oncogene addiction to LSF in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Despite
      the prevalence of HCC, there is no effective, systemic treatment. The
      transcription factor LSF is a promising protein target for chemotherapy; it is
      highly expressed in HCC patient samples and cell lines, and promotes oncogenesis
      in rodent xenograft models of HCC. Here, we identify small molecules that
      effectively inhibit LSF cellular activity. The lead compound, factor quinolinone
      inhibitor 1 (FQI1), inhibits LSF DNA-binding activity both in vitro, as
      determined by electrophoretic mobility shift assays, and in cells, as determined
      by ChIP. Consistent with such inhibition, FQI1 eliminates transcriptional
      stimulation of LSF-dependent reporter constructs. FQI1 also exhibits
      antiproliferative activity in multiple cell lines. In LSF-overexpressing cells,
      including HCC cells, cell death is rapidly induced; however, primary or
      immortalized hepatocytes are unaffected by treatment with FQI1. The highly
      concordant structure-activity relationship of a panel of 23 quinolinones strongly
      suggests that the growth inhibitory activity is due to a single biological target
      or family. Coupled with the striking agreement between the concentrations
      required for antiproliferative activity (GI(50)s) and for inhibition of LSF
      transactivation (IC(50)s), we conclude that LSF is the specific biological target
      of FQIs. Based on these in vitro results, we tested the efficacy of FQI1 in
      inhibiting HCC tumor growth in a mouse xenograft model. As a single agent, tumor
      growth was dramatically inhibited with no observable general tissue cytotoxicity.
      These findings support the further development of LSF inhibitors for cancer
      chemotherapy.

PMID- 22396592
TI  - Fanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A
      (FANCA) and participates in interstrand cross-link repair.
AB  - The Fanconi anemia (FA) pathway participates in interstrand cross-link (ICL)
      repair and the maintenance of genomic stability. The FA core complex consists of
      eight FA proteins and two Fanconi anemia-associated proteins (FAAP24 and
      FAAP100). The FA core complex has ubiquitin ligase activity responsible for
      monoubiquitination of the FANCI-FANCD2 (ID) complex, which in turn initiates a
      cascade of biochemical events that allow processing and removal of cross-linked
      DNA and thereby promotes cell survival following DNA damage. Here, we report the
      identification of a unique component of the FA core complex, namely, FAAP20,
      which contains a RAD18-like ubiquitin-binding zinc-finger domain. Our data
      suggest that FAAP20 promotes the functional integrity of the FA core complex via
      its direct interaction with the FA gene product, FANCA. Indeed, somatic knockout
      cells devoid of FAAP20 displayed the hallmarks of FA cells, including
      hypersensitivity to DNA cross-linking agents, chromosome aberrations, and reduced
      FANCD2 monoubiquitination. Taking these data together, our study indicates that
      FAAP20 is an important player involved in the FA pathway.

PMID- 22396590
TI  - Genetic dating indicates that the Asian-Papuan admixture through Eastern
      Indonesia corresponds to the Austronesian expansion.
AB  - Although the Austronesian expansion had a major impact on the languages of Island
      Southeast Asia, controversy still exists over the genetic impact of this
      expansion. The coexistence of both Asian and Papuan genetic ancestry in Eastern
      Indonesia provides a unique opportunity to address this issue. Here, we estimate
      recombination breakpoints in admixed genomes based on genome-wide SNP data and
      date the genetic admixture between populations of Asian vs. Papuan ancestry in
      Eastern Indonesia. Analyses of two genome-wide datasets indicate an eastward
      progression of the Asian admixture signal in Eastern Indonesia beginning about
      4,000-3,000 y ago, which is in excellent agreement with inferences based on
      Austronesian languages. The average rate of spread of Asian genes in Eastern
      Indonesia was about 0.9 km/y. Our results indicate that the Austronesian
      expansion had a strong genetic as well as linguistic impact on Island Southeast
      Asia, and they significantly advance our understanding of the biological origins
      of human populations in the Asia-Pacific region.

PMID- 22396594
TI  - Striated organelle, a cytoskeletal structure positioned to modulate hair-cell
      transduction.
AB  - The striated organelle (SO), a cytoskeletal structure located in the apical
      region of cochlear and vestibular hair cells, consists of alternating, cross
      linked, thick and thin filamentous bundles. In the vestibular periphery, the SO
      is well developed in both type I and type II hair cells. We studied the 3D
      structure of the SO with intermediate-voltage electron microscopy and electron
      microscope tomography. We also used antibodies to alpha-2 spectrin, one protein
      component, to trace development of the SO in vestibular hair cells over the first
      postnatal week. In type I cells, the SO forms an inverted open-ended cone
      attached to the cell membrane along both its upper and lower circumferences and
      separated from the cuticular plate by a dense cluster of exceptionally large
      mitochondria. In addition to contacts with the membrane and adjacent
      mitochondria, the SO is connected both directly and indirectly, via microtubules,
      to some stereociliary rootlets. The overall architecture of the apical region in
      type I hair cells--a striated structure restricting a cluster of large
      mitochondria between its filaments, the cuticular plate, and plasma membrane-
      suggests that the SO might serve two functions: to maintain hair-cell shape and
      to alter transduction by changing the geometry and mechanical properties of hair
      bundles.

PMID- 22396593
TI  - Polycomb repressive complex 2 is required for MLL-AF9 leukemia.
AB  - A growing body of data suggests the importance of epigenetic mechanisms in
      cancer. Polycomb repressive complex 2 (PRC2) has been implicated in self-renewal
      and cancer progression, and its components are overexpressed in many cancers.
      However, its role in cancer development and progression remains unclear. We used
      conditional alleles for the PRC2 components enhancer of zeste 2 (Ezh2) and
      embryonic ectoderm development (Eed) to characterize the role of PRC2 function in
      leukemia development and progression. Compared with wild-type leukemia, Ezh2-null
      MLL-AF9-mediated acute myeloid leukemia (AML) failed to accelerate upon secondary
      transplantation. However, Ezh2-null leukemias maintained self-renewal up to the
      third round of transplantation, indicating that Ezh2 is not strictly required for
      MLL-AF9 AML, but plays a role in leukemia progression. Genome-wide analyses of
      PRC2-mediated trimethylation of histone 3 demonstrated locus-specific persistence
      of H3K27me3 despite inactivation of Ezh2, suggesting partial compensation by
      Ezh1. In contrast, inactivation of the essential PRC2 gene, Eed, led to complete
      ablation of PRC2 function, which was incompatible with leukemia growth. Gene
      expression array analyses indicated more profound gene expression changes in Eed
      null compared with Ezh2-null leukemic cells, including down-regulation of Myc
      target genes and up-regulation of PRC2 targets. Manipulating PRC2 function may be
      of therapeutic benefit in AML.

PMID- 22396595
TI  - The mevalonate pathway regulates microRNA activity in Caenorhabditis elegans.
AB  - The mevalonate pathway is highly conserved and mediates the production of
      isoprenoids, which feed into biosynthetic pathways for sterols, dolichol,
      ubiquinone, heme, isopentenyl adenine, and prenylated proteins. We found that in
      Caenorhabditis elegans, the nonsterol biosynthetic outputs of the mevalonate
      pathway are required for the activity of microRNAs (miRNAs) in silencing their
      target mRNAs. Inactivation of genes that mediate multiple steps of the mevalonate
      pathway causes derepression of several miRNA target genes, with no disruption of
      the miRNA levels, suggesting a role in miRNA-induced silencing complex activity.
      Dolichol phosphate, synthesized from the mevalonate pathway, functions as a lipid
      carrier of the oligosaccharide moiety destined for protein N-linked
      glycosylation. Inhibition of the dolichol pathway of protein N-glycosylation also
      causes derepression of miRNA target mRNAs. The proteins that mediate miRNA
      repression are therefore likely to be regulated by N-glycosylation. Conversely,
      drugs such as statins, which inhibit the mevalonate pathway, may compromise miRNA
      repression as well as the more commonly considered cholesterol biosynthesis.

PMID- 22396598
TI  - Drug screen targeted at Plasmodium liver stages identifies a potent multistage
      antimalarial drug.
AB  - Plasmodium parasites undergo a clinically silent and obligatory developmental
      phase in the host's liver cells before they are able to infect erythrocytes and
      cause malaria symptoms. To overcome the scarcity of compounds targeting the liver
      stage of malaria, we screened a library of 1037 existing drugs for their ability
      to inhibit Plasmodium hepatic development. Decoquinate emerged as the strongest
      inhibitor of Plasmodium liver stages, both in vitro and in vivo. Furthermore,
      decoquinate kills the parasite's replicative blood stages and is active against
      developing gametocytes, the forms responsible for transmission. The drug acts by
      selectively and specifically inhibiting the parasite's mitochondrial bc(1)
      complex, with little cross-resistance with the antimalarial drug atovaquone. Oral
      administration of a single dose of decoquinate effectively prevents the
      appearance of disease, warranting its exploitation as a potent antimalarial
      compound.

PMID- 22396599
TI  - Production of interferon alpha by human immunodeficiency virus type 1 in human
      plasmacytoid dendritic cells is dependent on induction of autophagy.
AB  - BACKGROUND: The mechanisms responsible for interferon alpha (IFN-alpha)
      production by plasmacytoid dendritic cells (pDCs) during human immunodeficiency
      virus type 1 (HIV-1) infection are unknown. This research examined the roles of
      Toll-like receptor 7 (TLR7) and autophagy in IFN-alpha production by pDCs during
      HIV-1 infection. METHODS: pDCs from human peripheral blood mononuclear cells were
      incubated with infectious or aldrithiol 2 (AT-2)-inactivated HIV-1 or with
      uridine-rich single-stranded RNA40 (ssRNA40) from the HIV-1 long terminal repeat.
      IFN-alpha was quantified by enzyme-linked immunosorbant assay. Autophagic
      proteins were detected by Western blot, and autophagosomes were identified using
      immunofluorescent and confocal microscopy. To inhibit autophagy, pDCs were
      treated with the phosphoinositide-3 kinase inhibitor 3-methyladenine (3-MA) or
      were transfected with autophagy-related protein 7 or TLR7 small interfering RNA
      (siRNA). RESULTS: Increased levels of IFN-alpha were present in culture
      supernatants following 16-hour incubation of pDCs with infectious or AT-2
      inactivated HIV-1. Treatment of pDCs with ssRNA40 but not ssRNA41 resulted in
      high levels of IFN-alpha. pDCs exposed to HIV-1 gp120, rapamycin, or 3-MA alone
      failed to induce IFN-alpha. Pretreatment of pDCs with 3-MA significantly reduced
      the induction of IFN-alpha by ssRNA40. Similarly, knock down of autophagy-related
      protein 7 and TLR7 by use of siRNA significantly reduced the induction of IFN
      alpha by ssRNA40 or HIV-1. CONCLUSIONS: These findings demonstrate that IFN-alpha
      production by pDCs exposed to infectious or noninfectious HIV-1 and ssRNA40
      occurs through induction of autophagy following TLR7 signaling.

PMID- 22396600
TI  - Transmembrane domain membrane proximal external region but not surface unit
      directed broadly neutralizing HIV-1 antibodies can restrict dendritic cell
      mediated HIV-1 trans-infection.
AB  - BACKGROUND: Although broadly neutralizing antibodies (bNAbs) have been shown to
      block a diverse array of cell-free human immunodeficiency type 1 (HIV-1)
      infections, it remains unclear whether these antibodies exhibit similar potency
      against mature dendritic cell (mDC)-mediated HIV-1 trans-infection. METHODS:
      Sensitivity to bNAbs targeting HIV-1 envelope surface unit gp120 (VRCO1, PG16,
      b12, and 2G12) and transmembrane domain gp41 (4E10 and 2F5) was examined for both
      cell-free and mDC-mediated infections of TZM-bl and CD4(+) T cells. RESULTS:
      Compared with cell-free infection, mDC-mediated infection was significantly less
      susceptible to gp120-directed bNAbs for the majority of virus isolates. A b12
      antigen-binding fragment blocked both cell-free and mDC-mediated infection with
      equal efficiency. In contrast, cell-free and mDC-associated viruses were equally
      sensitive to gp41-directed bNAbs. Anti-gp41 bNAbs bound to the surface of mDCs
      and localized at the mDC-T cell synaptic junctions in the absence of virus.
      CONCLUSIONS: Anti-gp41 bNAbs have the potential to inhibit mDC-mediated HIV-1
      infection because they bind plasma membranes prior to the formation of an
      infectious synapse, positioning them to neutralize subsequent virus transfer. As
      opposed to gp120-directed antibodies, anti-gp41 bNAbs might prevent HIV-1
      infection if transmission or spread at the initial site of invasion occurs from a
      DC-associated source.

PMID- 22396602
TI  - Economic evaluation in patient safety: a literature review of methods.
AB  - Patient safety practices, targeting organisational changes for improving patient
      safety, are implemented worldwide but their costs are rarely evaluated. This
      paper provides a review of the methods used in economic evaluation of such
      practices. International medical and economics databases were searched for peer
      reviewed publications on economic evaluations of patient safety between 2000 and
      2010 in English and French. This was complemented by a manual search of the
      reference lists of relevant papers. Grey literature was excluded. Studies were
      described using a standardised template and assessed independently by two
      researchers according to six quality criteria. 33 articles were reviewed that
      were representative of different patient safety domains, data types and
      evaluation methods. 18 estimated the economic burden of adverse events, 3
      measured the costs of patient safety practices and 12 provided complete economic
      evaluations. Healthcare-associated infections were the most common subject of
      evaluation, followed by medication-related errors and all types of adverse
      events. Of these, 10 were selected that had adequately fulfilled one or several
      key quality criteria for illustration. This review shows that full cost
      benefit/utility evaluations are rarely completed as they are resource intensive
      and often require unavailable data; some overcome these difficulties by
      performing stochastic modelling and by using secondary sources. Low
      methodological transparency can be a problem for building evidence from available
      economic evaluations. Investing in the economic design and reporting of studies
      with more emphasis on defining study perspectives, data collection and
      methodological choices could be helpful for strengthening our knowledge base on
      practices for improving patient safety.

PMID- 22396603
TI  - Giant intracranial aneurysm of the right middle cerebral artery.

PMID- 22396601
TI  - Male human papillomavirus prevalence and association with condom use in Brazil,
      Mexico, and the United States.
AB  - BACKGROUND: Reported associations of condom use and human papillomavirus (HPV)
      infection have been inconsistent. We investigated self-reported frequency of
      condom use and detection of genital HPV among men. METHODS: A cross-sectional
      analysis was conducted in men aged 18-70 years from Brazil, Mexico, and the
      United States. Men completed questionnaires on sexual history, condom use, and
      sociodemographic characteristics. Among 2621 men reporting recent vaginal sex,
      prevalence of any HPV, any oncogenic type, and nononcogenic types only was
      estimated by frequency of condom use ("always" or "not always"). Multivariable
      models were used to estimate prevalence ratios (PRs) for HPV according to
      frequency of condom use. RESULTS: The prevalence of any HPV was 70.5%; any
      oncogenic type, 34%, and nononcogenic types only, 22.2%. The adjusted PR for
      always vs not always using condoms was 0.87 (95% confidence interval [CI], .77
      .97) for all countries combined. The association was stronger in the United
      States (PR, 0.70; CI, .55-.90) than in Brazil (PR, 0.84; CI, .71-1.01) or Mexico
      (PR, 1.05; CI, .89-1.25) (P for interaction = .025). CONCLUSIONS: HPV prevalence
      was high even among those who reported always using condoms, and its associations
      with always using condoms varied among countries.

PMID- 22396604
TI  - Endobronchial ultrasound transbronchial needle aspiration at Aberdeen Royal
      Infirmary: the initial experience.

PMID- 22396605
TI  - Is superolateral Hoffa fat pad edema a consequence of impingement between lateral
      femoral condyle and patellar ligament?
AB  - PURPOSE: To evaluate whether knee extensor mechanism features are associated with
      superolateral Hoffa fat pad edema at magnetic resonance imaging. MATERIALS AND
      METHODS: Institutional review board approval and written consent from all
      patients were obtained. Patients with superolateral Hoffa fat pad edema (n = 30)
      and a control group without edema of the fat pad (n = 60) were evaluated
      prospectively with magnetic resonance (MR) imaging. Demographic data and extensor
      mechanism features were compared, including trochlear depth, lateral trochlear
      inclination, patellar tilt angle, patellar height ratio, distance between
      patellar ligament and lateral trochlear facet, distance from the tibial tubercle
      to the trochlear groove, patellar facet asymmetry, and patellar ligament
      abnormalities. RESULTS: The following variables were associated with
      superolateral Hoffa fat pad edema in the multivariable models: patellar height
      ratio (P = .023), shortest distance between patellar ligament and lateral
      trochlear facet (P < .001), and distance from the tibial tubercle to the
      trochlear groove (P = .046). Of all demographic and degenerative variables, only
      age was significantly associated, with younger patients more likely to have
      superolateral Hoffa fat pad edema (P < .009). CONCLUSION: A high-riding patella,
      a short distance between the patellar ligament and the lateral trochlear facet,
      and an increased distance from the tibial tubercle to the trochlear groove are
      associated with superolateral Hoffa fat pad edema at MR imaging. These results
      are suggestive of impingement between the lateral femoral condyle and the
      posterior aspect of the patellar ligament in these patients.

PMID- 22396606
TI  - Lung morphology assessment with balanced steady-state free precession MR imaging
      compared with CT.
AB  - PURPOSE: To evaluate the utility of 1.5-T noncontrast magnetic resonance (MR)
      imaging of the lung parenchyma and to compare it with computed tomography (CT) in
      the assessment of interstitial lung disease and other morphologic lung
      abnormalities. MATERIALS AND METHODS: Institutional review board approval was
      obtained for retrospective image analysis. A total of 236 patients who underwent
      MR imaging and CT as part of their assessment for suspected pulmonary
      hypertension were included in this study. Lung MR imaging was performed with a
      1.5-T system as a stack of axial two-dimensional balanced steady-state free
      precession (bSSFP) acquisitions. Two radiologists independently evaluated CT and
      MR images for various morphologic abnormalities, such as pulmonary fibrosis,
      pleural and mediastinal disease, solid lesions, bronchial disease, and emphysema.
      Kappa statistics were used to measure interobserver agreement. RESULTS:
      Sensitivity and specificity of MR imaging in the identification of pulmonary
      fibrosis (n = 46) were 89% (95% confidence interval: 77%, 96%) and 91% (95%
      confidence interval: 76%, 98%), respectively, when compared with CT. In
      comparison to CT, MR imaging depicted 75% of ground-glass opacities. Nine of the
      12 noncalcified nodules were identified on MR images. Lung nodules (75%, kappa =
      0.71) and effusions (100%, kappa = 0.89) were also well visualized on MR images.
      MR imaging was however less effective in depicting emphysema (16%, kappa = 0.60)
      and minor fibrosis (67%, kappa = 0.79). CONCLUSION: This study shows bSSFP MR
      imaging is inferior to CT in imaging parenchymal lung disease; however, this
      study does demonstrate for the first time a potential role for the bSSFP sequence
      as an alternative radiation-free noncontrast imaging modality for use in patients
      with pulmonary fibrosis.

PMID- 22396607
TI  - Real-time sonoelastography for the evaluation of testicular lesions.
AB  - PURPOSE: To evaluate the feasibility of using real-time sonoelastography (RTE)
      for the differentiation and characterization of testicular lesions. MATERIALS AND
      METHODS: Institutional review board approval was obtained for this retrospective
      study, and the requirement to obtain informed consent was waived. Fifty patients
      (mean age, 42 years; age range, 18-81 years) with testicular lesions detected
      with gray-scale ultrasonography (US) and color and/or power Doppler US were
      evaluated with RTE between December 2004 and August 2010 to assess tissue
      elasticity of the testes. Stiff or "hard" lesions were suspected of being
      malignant. Testicular lesions with normal or decreased tissue stiffness ("soft"
      lesions) were considered benign. Findings from surgery and histopathologic
      examination were used as the reference standard in 34 cases, and findings from
      clinical and US follow-up were used as the reference standard in 16 cases.
      Sensitivity, specificity, negative predictive value, positive predictive value,
      and diagnostic accuracy were calculated. RESULTS: Thirty-four of the 50 lesions
      (68%) were testicular tumors and 16 (32%) were of nontumorous origin. RTE showed
      the presence of hard lesions in all cases of testicular tumors and three cases of
      nontumorous lesions. Four lesions with an uncertain diagnosis when tested with
      gray-scale US and color and/or power Doppler US alone were soft at RTE and showed
      nontumorous character at follow-up. RTE showed a sensitivity of 100%, a
      specificity of 81%, a negative predictive value of 100%, a positive predictive
      value of 92%, and an accuracy of 94% in the diagnosis of testicular tumors.
      CONCLUSION: RTE demonstrated all testicular tumors as lesions with increased
      tissue stiffness. Because of its higher specificity, RTE can provide additional
      information in cases with indeterminate US findings.

PMID- 22396608
TI  - No evidence for association of Chr 9p21 variant rs1333049 with gout in New
      Zealand case-control sample sets.

PMID- 22396609
TI  - A new challenge for the tuberculosis vaccine community?

PMID- 22396618
TI  - The current status and issues regarding hospital-based specialized palliative
      care service in Japanese Regional Cancer Centers: a nationwide questionnaire
      survey.
AB  - OBJECTIVE: Palliative care consultation teams have become part of all Japanese
      regional cancer centers. However, the current status and issues regarding
      specialized palliative care service in the cancer centers have yet to be
      clarified. Therefore, we conducted a nationwide survey of the current status of
      palliative care service in all Japanese regional cancer centers in 2007. METHODS:
      A self-reported cross-sectional survey questionnaire was mailed to all regional
      cancer centers in Japan. The structure and process of activities of palliative
      care service were included in the survey questions. RESULTS: A total of 242 of
      288 institutions (84%) returned the questionnaires. Responses indicated that 99%
      had palliative care consultation teams. For the structure of palliative care
      consultation service, there were 73 +/- 133 (mean +/- standard deviation)
      referred patients per year and ~ 90% had discharge and home care support for
      patients who needed palliative care; 31% had no available consultation service
      during the daytime on weekdays. For the process of palliative care consultation
      service, 90% defined the palliative care consultation request methods, 92%
      implemented seminars about palliative care for health-care workers in the
      hospital and 31% had joint meetings with the clinics and home nursing station in
      the community. CONCLUSIONS: Palliative care services have rapidly been developed
      and implemented in Japan. However, to improve the quality of palliative care
      services and provide more specialized palliative care within the limits of
      resources, it will be necessary to review the system in the future.

PMID- 22396610
TI  - A human challenge model for Mycobacterium tuberculosis using Mycobacterium bovis
      bacille Calmette-Guerin.
AB  - BACKGROUND: There is currently no safe human challenge model of Mycobacterium
      tuberculosis infection to enable proof-of-concept efficacy evaluation of
      candidate vaccines against tuberculosis. In vivo antimycobacterial immunity could
      be assessed using intradermal Mycobacterium bovis bacille Calmette-Guerin (BCG)
      vaccination as a surrogate for M. tuberculosis infection. METHODS: Healthy BCG
      naive and BCG-vaccinated volunteers were challenged with intradermal BCG. BCG
      load was quantified from skin biopsy specimens by polymerase chain reaction (PCR)
      and culture colony-forming units. Cellular infiltrate was isolated by suction
      blisters and examined by flow cytometry. Prechallenge immune readouts were
      correlated with BCG load after challenge. RESULTS: In BCG-naive volunteers, live
      BCG was detected at the challenge site for up to 4 weeks and peaked at 2 weeks.
      Infiltration of mainly CD15(+) neutrophils was observed in blister fluid. In
      previously BCG-vaccinated individuals, PCR analysis of skin biopsy specimens
      reflected a degree of mycobacterial immunity. There was no significant
      correlation between BCG load after challenge and mycobacterial-specific memory T
      cells measured before challenge by cultured enzyme-linked immunospot assay.
      CONCLUSIONS: This novel experimental human challenge model provides a platform
      for the identification of correlates of antimycobacterial immunity and will
      greatly facilitate the rational down-selection of candidate tuberculosis
      vaccines. Further evaluation of this model with BCG and new vaccine candidates is
      warranted.

PMID- 22396619
TI  - Systematic lymphadenectomy for survival in patients with endometrial cancer: a
      meta-analysis.
AB  - OBJECTIVE: The efficacy of systematic lymphadenectomy is controversial for
      improving overall survival in patients with endometrial cancer. Thus, we
      performed a meta-analysis comparing the efficacy for overall survival between
      systematic and unsystematic lymphadenectomies. METHODS: After an extensive
      literature search between January 2000 and August 2010, we analyzed nine studies
      (two randomized controlled trials and seven observational studies) involving 16
      995 patients with endometrial cancer. Systematic versus unsystematic
      lymphadenectomy was defined using two criteria: removal of >=10-11 versus <=10-11
      lymph nodes; systematic dissection of lymphatic tissues versus no lymphadenectomy
      other than suspicious lymph nodes. RESULTS: In all studies, systematic
      lymphadenectomy improved overall survival, compared with unsystematic
      lymphadenectomy (hazard ratio, 0.89; 95% confidence interval, 0.82-0.97), whereas
      its efficacy was not shown in two randomized controlled trials (hazard ratio,
      1.05; 95% confidence interval, 0.84-1.31). Removal of >=10-11 lymph nodes
      improved overall survival, compared with that of <=10-11 lymph nodes (hazard
      ratio, 0.88; 95% confidence interval, 0.81-0.97) in spite of no difference in
      overall survival between systematic dissection of lymphatic tissues and no
      lymphadenectomy other than suspicious lymph nodes (hazard ratio, 0.94; 95%
      confidence interval, 0.77-1.15). Furthermore, systematic lymphadenectomy
      increased overall survival in patients with intermediate- or high-risk
      endometrial cancer (hazard ratio, 0.77; 95% confidence interval, 0.70-0.86) in
      spite of no efficacy in those with low-risk endometrial cancer (hazard ratio,
      1.14; 95% confidence interval, 0.87-1.49). CONCLUSIONS: These findings suggest
      that the efficacy of systematic lymphadenectomy, defined as removal of more than
      about 10 lymph nodes, is limited for improving overall survival in patients with
      low-risk endometrial cancer, whereas it is efficient to increase overall survival
      in patients with intermediate- or high-risk endometrial cancer.

PMID- 22396621
TI  - Periodically focused modes in chains of dielectric spheres.
AB  - We show that, theoretically, Brewster angle conditions for transverse magnetic
      polarized rays can be periodically reproduced in chains of spheres with index n =
      [Formula: see text] giving rise to lossless periodically focused modes with 2D
      period, where D is the sphere diameter. Using ray tracing for a spherical emitter
      with the diameter D we show that chains of spheres work as filters of such modes
      at 1.72 < n < 1.85. This leads to tapering of the focused beams combined with the
      reduction of their attenuation along the chain. Experimentally, the "beam
      tapering" effect was observed in chains of 300 MUm sapphire spheres with index
      ~1.77 in visible.

PMID- 22396620
TI  - Cell surface localization and release of the candidate tumor suppressor Ecrg4
      from polymorphonuclear cells and monocytes activate macrophages.
AB  - We identified fresh human leukocytes as an abundant source of the candidate
      epithelial tumor suppressor gene, Ecrg4, an epigenetically regulated gene, which
      unlike other tumor suppressor genes, encodes an orphan-secreted, ligand-like
      protein. In human cell lines, Ecrg4 gene expression was low, Ecrg4 protein
      undetectable, and Ecrg4 promoter hypermethylation high (45-90%) and reversible by
      the methylation inhibitor 5-AzaC. In contrast, Ecrg4 gene expression in fresh,
      normal human PBMCs and PMNs was 600-800 times higher than in cultured cell lines,
      methylation of the Ecrg4 promoter was low (<3%), and protein levels were readily
      detectable in lysates and on the cell surface. Flow cytometry, immunofluorescent
      staining, and cell surface biotinylation established that full-length, 14-kDa
      Ecrg4 was localized on PMN and monocyte cell surfaces, establishing that Ecrg4 is
      a membrane-anchored protein. LPS treatment induced processing and release of
      Ecrg4, as detected by flow and immunoblotting, whereas an effect of fMLF
      treatment on Ecrg4 on the PMN cell surface was detected on the polarized R2
      subpopulation of cells. This loss of cell surface Ecrg4 was associated with the
      detection of intact and processed Ecrg4 in the conditioned media of fresh
      leukocytes and was shown to be associated with the inflammatory response that
      follows severe, cutaneous burn injury. Furthermore, incubation of macrophages
      with a soluble Ecrg4-derived peptide increased the P-p65, suggesting that
      processing of an intact sentinel Ecrg4 on quiescent circulating leukocytes leads
      to processing from the cell surface following injury and macrophage activation.

PMID- 22396622
TI  - Use of the radiofrequency-intermodulation distortion technique to investigate
      intrinsic nonlinearity at the electrode-electrolyte interface.
AB  - We report on investigations of nonlinear radiofrequency responses of electrolytes
      with Na(+) and Cl(-) ions placed within gold electrodes of a capacitor. The
      sample was part of a frequency-adjustable inductance-capacitance-resistance (LCR)
      parallel resonant circuit, and measurements were carried out using the two
      frequencies intermodulation distortion technique. We employed double layer model
      to analyze the observed nonlinearities and their dependence on ionic
      concentration. Electrode-electrolyte interface polarization was found to be a
      predominant cause of this intrinsic nonlinearity and to be dependent on
      electrolytic ion concentration. We also measured and calculated coefficients of
      resistive and capacitive components of the observed nonlinearity.

PMID- 22396623
TI  - Optical anisotropy in self-assembled InAs nanostructures grown on GaAs high index
      substrate.
AB  - We present a study of the optical properties of InAs self-assembled
      nanostructures grown by molecular beam epitaxy on GaAs(11N)A substrates (N = 3
      5). Photoluminescence (PL) measurements revealed good optical properties of InAs
      quantum dots (QDs) grown on GaAs(115)A compared to those grown on GaAs(113)A and
      (114)A orientations substrate. An additional peak localized at 1.39 eV has been
      shown on PL spectra of both GaAs(114)A and (113)A samples. This peak persists
      even at lower power density. Supporting on the polarized photoluminescence
      characterization, we have attributed this additional peak to the quantum strings
      (QSTs) emission. A theoretical study based on the resolution of the three
      dimensional Schrodinger equation, using the finite element method, including
      strain and piezoelectric-field effect was adopted to distinguish the observed
      photoluminescence emission peaks. The mechanism of QDs and QSTs formation on such
      a high index GaAs substrates was explained in terms of piezoelectric driven atoms
      and the equilibrium surfaces at edges.

PMID- 22396624
TI  - Excitation wavelength dependence of water-window line emissions from boron
      nitride laser-produced plasmas.
AB  - We investigated the effects of laser excitation wavelength on water-window
      emission lines of laser-produced boron-nitride plasmas. Plasmas are produced by
      focusing 1064 nm and harmonically generated 532 and 266 nm radiation from a
      Nd:YAG laser on BN target in vacuum. Soft x-ray emission lines in the water
      window region are recorded using a grazing-incidence spectrograph. Filtered
      photodiodes are used to obtain complementary data for water-window emission
      intensity and angular dependence. Spectral emission intensity changes in nitrogen
      Ly-alpha and He-alpha are used to show how laser wavelength affects emission. Our
      results show that the relative intensity of spectral lines is laser wavelength
      dependent, with the ratio of Ly-alpha to He-alpha emission intensity decreasing
      as laser wavelength is shortened. Filtered photodiode measurements of angular
      dependence showed that 266 and 532 nm laser wavelengths produce uniform emission.

PMID- 22396625
TI  - A case of typical pulmonary carcinoid tumor treated with bronchoscopic therapy
      followed by lobectomy.
AB  - Carcinoid bronchopulmonary tumors represent approximately 25% of all carcinoid
      tumors and 1%-2% of all lung neoplasms. The most common symptoms are: persistent
      cough, asthma-like wheezing, chest pain, dyspnea, hemoptysis and obstructive
      pneumonitis. We present a case of a young adult diagnosed with a typical
      carcinoid tumor. The diagnosis was established on the basis of imaging
      examination and bronchoscopic biopsy. The patient was treated with bronchoscopic
      electrocautery therapy to relieve the obstructed airway, followed by surgical
      lobectomy in order to entirely remove the exophytic damage. This approach was not
      only a palliative management to bronchial obstruction but also avoided
      pneumonectomy. Recent studies support the use of such interventional resection
      methods, as they may result in a more conservative surgical resection.

PMID- 22396626
TI  - Motivators, enablers, and barriers to building allied health research capacity.
AB  - PURPOSE: A sound, scientific base of high quality research is needed to inform
      service planning and decision making and enable improved policy and practice.
      However, some areas of health practice, particularly many of the allied health
      areas, are generally considered to have a low evidence base. In order to
      successfully build research capacity in allied health, a clearer understanding is
      required of what assists and encourages research as well as the barriers and
      challenges. PARTICIPANTS AND METHODS: This study used written surveys to collect
      data relating to motivators, enablers, and barriers to research capacity
      building. Respondents were asked to answer questions relating to them as
      individuals and other questions relating to their team. Allied health
      professionals were recruited from multidisciplinary primary health care teams in
      Queensland Health. Eighty-five participants from ten healthcare teams completed a
      written version of the research capacity and culture survey. RESULTS: The results
      of this study indicate that individual allied health professionals are more
      likely to report being motivated to do research by intrinsic factors such as a
      strong interest in research. Barriers they identified to research are more likely
      to be extrinsic factors such as workload and lack of time. Allied health
      professionals identified some additional factors that impact on their research
      capacity than those reported in the literature, such as a desire to keep at the
      "cutting edge" and a lack of exposure to research. Some of the factors
      influencing individuals to do research were different to those influencing teams.
      These results are discussed with reference to organizational behavior and
      theories of motivation. CONCLUSION: Supporting already motivated allied health
      professional individuals and teams to conduct research by increased skills
      training, infrastructure, and quarantined time is likely to produce better
      outcomes for research capacity building investment.

PMID- 22396627
TI  - Volunteering in dementia care - a Norwegian phenomenological study.
AB  - INTRODUCTION: The number of people suffering from dementia will increase
      dramatically in the future, and this will be a great challenge and concern for
      health care services. It is assumed that volunteers will strengthen community
      health care services more in the future than they do today. AIM: The aim of this
      study was to elucidate lived experiences of working as a volunteer in an activity
      center with adapted activities for home-dwelling people with early stage
      dementia. METHODS: Qualitative interviews were implemented in a group of nine
      female volunteers from an activity center in southern Norway. The interviews were
      recorded, transcribed verbatim, and analyzed with a descriptive phenomenological
      method. RESULTS: Volunteering in an activity center for home-dwelling people with
      early stage dementia was reported to provide experiences of being useful and
      feeling satisfied with performing a good job. It was an advantage for the
      volunteers to have had experiences from life in general, but also as a health
      professional or as being the next of kin of a dementia sufferer. It was important
      for the volunteers to focus on the dementia sufferer and show caring behavior,
      and interaction with and the appreciation of the health care professionals were
      also important. The volunteers were motivated by being able to have influence and
      participate in the planning of the work, to be a part of the social setting, and
      to learn. However, for some volunteers it was difficult to adjust to an
      appropriate role. CONCLUSION: In order to promote volunteering in a caring
      context, mutual trust and freedom should be emphasized. Being conscious of
      important volunteer characteristics like their experiences, knowledge, and caring
      behavior, as well as a focus on the staff showing appreciation and providing
      feedback, may be the difference between success and failure.

PMID- 22396628
TI  - Development of a detailed log booklet for social ecological physical activity
      research.
AB  - To advance social ecological research, tools are required to better assess the
      contextual nature of physical activity outcomes. This study describes the
      development of a detailed log booklet to capture relevant episode-specific data,
      including location and purpose, about participants' free-living activity
      patterns. The log was developed using definitions and questions from existing
      physical activity questionnaires as well as measures designed to elicit more
      specific and detailed information relevant to social ecological studies of
      physical activity. Utility of the log was tested with 580 community residents
      over seven days. It was found to be practical and feasible for use in community
      based physical activity research, and yielded a wealth of episodic information
      about intensity, duration, location, purpose, and co-participants, among other
      details.

PMID- 22396629
TI  - Efficient sparse coding in early sensory processing: lessons from signal
      recovery.
AB  - Sensory representations are not only sparse, but often overcomplete: coding units
      significantly outnumber the input units. For models of neural coding this
      overcompleteness poses a computational challenge for shaping the signal
      processing channels as well as for using the large and sparse representations in
      an efficient way. We argue that higher level overcompleteness becomes
      computationally tractable by imposing sparsity on synaptic activity and we also
      show that such structural sparsity can be facilitated by statistics based
      decomposition of the stimuli into typical and atypical parts prior to sparse
      coding. Typical parts represent large-scale correlations, thus they can be
      significantly compressed. Atypical parts, on the other hand, represent local
      features and are the subjects of actual sparse coding. When applied on natural
      images, our decomposition based sparse coding model can efficiently form
      overcomplete codes and both center-surround and oriented filters are obtained
      similar to those observed in the retina and the primary visual cortex,
      respectively. Therefore we hypothesize that the proposed computational
      architecture can be seen as a coherent functional model of the first stages of
      sensory coding in early vision.

PMID- 22396630
TI  - Depression-biased reverse plasticity rule is required for stable learning at top
      down connections.
AB  - Top-down synapses are ubiquitous throughout neocortex and play a central role in
      cognition, yet little is known about their development and specificity. During
      sensory experience, lower neocortical areas are activated before higher ones,
      causing top-down synapses to experience a preponderance of post-synaptic activity
      preceding pre-synaptic activity. This timing pattern is the opposite of that
      experienced by bottom-up synapses, which suggests that different versions of
      spike-timing dependent synaptic plasticity (STDP) rules may be required at top
      down synapses. We consider a two-layer neural network model and investigate which
      STDP rules can lead to a distribution of top-down synaptic weights that is
      stable, diverse and avoids strong loops. We introduce a temporally reversed rule
      (rSTDP) where top-down synapses are potentiated if post-synaptic activity
      precedes pre-synaptic activity. Combining analytical work and integrate-and-fire
      simulations, we show that only depression-biased rSTDP (and not classical STDP)
      produces stable and diverse top-down weights. The conclusions did not change upon
      addition of homeostatic mechanisms, multiplicative STDP rules or weak external
      input to the top neurons. Our prediction for rSTDP at top-down synapses, which
      are distally located, is supported by recent neurophysiological evidence showing
      the existence of temporally reversed STDP in synapses that are distal to the post
      synaptic cell body.

PMID- 22396631
TI  - Uncovering the dynamics of cardiac systems using stochastic pacing and frequency
      domain analyses.
AB  - Alternans of cardiac action potential duration (APD) is a well-known
      arrhythmogenic mechanism which results from dynamical instabilities. The
      propensity to alternans is classically investigated by examining APD restitution
      and by deriving APD restitution slopes as predictive markers. However,
      experiments have shown that such markers are not always accurate for the
      prediction of alternans. Using a mathematical ventricular cell model known to
      exhibit unstable dynamics of both membrane potential and Ca2+ cycling, we
      demonstrate that an accurate marker can be obtained by pacing at cycle lengths
      (CLs) varying randomly around a basic CL (BCL) and by evaluating the transfer
      function between the time series of CLs and APDs using an autoregressive-moving
      average (ARMA) model. The first pole of this transfer function corresponds to the
      eigenvalue (lambda(alt)) of the dominant eigenmode of the cardiac system, which
      predicts that alternans occurs when lambda(alt) <= -1. For different BCLs,
      control values of lambda(alt) were obtained using eigenmode analysis and compared
      to the first pole of the transfer function estimated using ARMA model fitting in
      simulations of random pacing protocols. In all versions of the cell model, this
      pole provided an accurate estimation of lambda(alt). Furthermore, during slow
      ramp decreases of BCL or simulated drug application, this approach predicted the
      onset of alternans by extrapolating the time course of the estimated lambda(alt).
      In conclusion, stochastic pacing and ARMA model identification represents a novel
      approach to predict alternans without making any assumptions about its ionic
      mechanisms. It should therefore be applicable experimentally for any type of
      myocardial cell.

PMID- 22396632
TI  - A self-organizing state-space-model approach for parameter estimation in hodgkin
      huxley-type models of single neurons.
AB  - Traditional approaches to the problem of parameter estimation in biophysical
      models of neurons and neural networks usually adopt a global search algorithm
      (for example, an evolutionary algorithm), often in combination with a local
      search method (such as gradient descent) in order to minimize the value of a cost
      function, which measures the discrepancy between various features of the
      available experimental data and model output. In this study, we approach the
      problem of parameter estimation in conductance-based models of single neurons
      from a different perspective. By adopting a hidden-dynamical-systems formalism,
      we expressed parameter estimation as an inference problem in these systems, which
      can then be tackled using a range of well-established statistical inference
      methods. The particular method we used was Kitagawa's self-organizing state-space
      model, which was applied on a number of Hodgkin-Huxley-type models using
      simulated or actual electrophysiological data. We showed that the algorithm can
      be used to estimate a large number of parameters, including maximal conductances,
      reversal potentials, kinetics of ionic currents, measurement and intrinsic noise,
      based on low-dimensional experimental data and sufficiently informative priors in
      the form of pre-defined constraints imposed on model parameters. The algorithm
      remained operational even when very noisy experimental data were used.
      Importantly, by combining the self-organizing state-space model with an adaptive
      sampling algorithm akin to the Covariance Matrix Adaptation Evolution Strategy,
      we achieved a significant reduction in the variance of parameter estimates. The
      algorithm did not require the explicit formulation of a cost function and it was
      straightforward to apply on compartmental models and multiple data sets. Overall,
      the proposed methodology is particularly suitable for resolving high-dimensional
      inference problems based on noisy electrophysiological data and, therefore, a
      potentially useful tool in the construction of biophysical neuron models.

PMID- 22396633
TI  - How cells integrate complex stimuli: the effect of feedback from
      phosphoinositides and cell shape on cell polarization and motility.
AB  - To regulate shape changes, motility and chemotaxis in eukaryotic cells, signal
      transduction pathways channel extracellular stimuli to the reorganization of the
      actin cytoskeleton. The complexity of such networks makes it difficult to
      understand the roles of individual components, let alone their interactions and
      multiple feedbacks within a given layer and between layers of signalling. Even
      more challenging is the question of if and how the shape of the cell affects and
      is affected by this internal spatiotemporal reorganization. Here we build on our
      previous 2D cell motility model where signalling from the Rho family GTPases
      (Cdc42, Rac, and Rho) was shown to organize the cell polarization, actin
      reorganization, shape change, and motility in simple gradients. We extend this
      work in two ways: First, we investigate the effects of the feedback between the
      phosphoinositides (PIs) PIP2, PIP3 and Rho family GTPases. We show how that
      feedback increases heights and breadths of zones of Cdc42 activity, facilitating
      global communication between competing cell "fronts". This hastens the commitment
      to a single lamellipodium initiated in response to multiple, complex, or rapidly
      changing stimuli. Second, we show how cell shape feeds back on internal
      distribution of GTPases. Constraints on chemical isocline curvature imposed by
      boundary conditions results in the fact that dynamic cell shape leads to faster
      biochemical redistribution when the cell is repolarized. Cells with frozen
      cytoskeleton, and static shapes, consequently respond more slowly to reorienting
      stimuli than cells with dynamic shape changes, the degree of the shape-induced
      effects being proportional to the extent of cell deformation. We explain these
      concepts in the context of several in silico experiments using our 2D
      computational cell model.

PMID- 22396634
TI  - Exploring the evolution of novel enzyme functions within structurally defined
      protein superfamilies.
AB  - In order to understand the evolution of enzyme reactions and to gain an overview
      of biological catalysis we have combined sequence and structural data to generate
      phylogenetic trees in an analysis of 276 structurally defined enzyme
      superfamilies, and used these to study how enzyme functions have evolved. We
      describe in detail the analysis of two superfamilies to illustrate different
      paradigms of enzyme evolution. Gathering together data from all the superfamilies
      supports and develops the observation that they have all evolved to act on a
      diverse set of substrates, whilst the evolution of new chemistry is much less
      common. Despite that, by bringing together so much data, we can provide a
      comprehensive overview of the most common and rare types of changes in function.
      Our analysis demonstrates on a larger scale than previously studied, that
      modifications in overall chemistry still occur, with all possible changes at the
      primary level of the Enzyme Commission (E.C.) classification observed to a
      greater or lesser extent. The phylogenetic trees map out the evolutionary route
      taken within a superfamily, as well as all the possible changes within a
      superfamily. This has been used to generate a matrix of observed exchanges from
      one enzyme function to another, revealing the scale and nature of enzyme
      evolution and that some types of exchanges between and within E.C. classes are
      more prevalent than others. Surprisingly a large proportion (71%) of all known
      enzyme functions are performed by this relatively small set of 276 superfamilies.
      This reinforces the hypothesis that relatively few ancient enzymatic domain
      superfamilies were progenitors for most of the chemistry required for life.

PMID- 22396635
TI  - Cortical Surround Interactions and Perceptual Salience via Natural Scene
      Statistics.
AB  - Spatial context in images induces perceptual phenomena associated with salience
      and modulates the responses of neurons in primary visual cortex (V1). However,
      the computational and ecological principles underlying contextual effects are
      incompletely understood. We introduce a model of natural images that includes
      grouping and segmentation of neighboring features based on their joint
      statistics, and we interpret the firing rates of V1 neurons as performing optimal
      recognition in this model. We show that this leads to a substantial
      generalization of divisive normalization, a computation that is ubiquitous in
      many neural areas and systems. A main novelty in our model is that the influence
      of the context on a target stimulus is determined by their degree of statistical
      dependence. We optimized the parameters of the model on natural image patches,
      and then simulated neural and perceptual responses on stimuli used in classical
      experiments. The model reproduces some rich and complex response patterns
      observed in V1, such as the contrast dependence, orientation tuning and spatial
      asymmetry of surround suppression, while also allowing for surround facilitation
      under conditions of weak stimulation. It also mimics the perceptual salience
      produced by simple displays, and leads to readily testable predictions. Our
      results provide a principled account of orientation-based contextual modulation
      in early vision and its sensitivity to the homogeneity and spatial arrangement of
      inputs, and lends statistical support to the theory that V1 computes visual
      salience.

PMID- 22396636
TI  - Modelling the self-assembly of elastomeric proteins provides insights into the
      evolution of their domain architectures.
AB  - Elastomeric proteins have evolved independently multiple times through evolution.
      Produced as monomers, they self-assemble into polymeric structures that impart
      properties of stretch and recoil. They are composed of an alternating domain
      architecture of elastomeric domains interspersed with cross-linking elements.
      While the former provide the elasticity as well as help drive the assembly
      process, the latter serve to stabilise the polymer. Changes in the number and
      arrangement of the elastomeric and cross-linking regions have been shown to
      significantly impact their assembly and mechanical properties. However, to date,
      such studies are relatively limited. Here we present a theoretical study that
      examines the impact of domain architecture on polymer assembly and integrity. At
      the core of this study is a novel simulation environment that uses a model of
      diffusion limited aggregation to simulate the self-assembly of rod-like particles
      with alternating domain architectures. Applying the model to different domain
      architectures, we generate a variety of aggregates which are subsequently
      analysed by graph-theoretic metrics to predict their structural integrity. Our
      results show that the relative length and number of elastomeric and cross-linking
      domains can significantly impact the morphology and structural integrity of the
      resultant polymeric structure. For example, the most highly connected polymers
      were those constructed from asymmetric rods consisting of relatively large cross
      linking elements interspersed with smaller elastomeric domains. In addition to
      providing insights into the evolution of elastomeric proteins, simulations such
      as those presented here may prove valuable for the tuneable design of new
      molecules that may be exploited as useful biomaterials.

PMID- 22396637
TI  - Changes in Lysozyme Flexibility upon Mutation Are Frequent, Large and Long
      Ranged.
AB  - We investigate changes in human c-type lysozyme flexibility upon mutation via a
      Distance Constraint Model, which gives a statistical mechanical treatment of
      network rigidity. Specifically, two dynamical metrics are tracked. Changes in
      flexibility index quantify differences within backbone flexibility, whereas
      changes in the cooperativity correlation quantify differences within pairwise
      mechanical couplings. Regardless of metric, the same general conclusions are
      drawn. That is, small structural perturbations introduced by single point
      mutations have a frequent and pronounced affect on lysozyme flexibility that can
      extend over long distances. Specifically, an appreciable change occurs in
      backbone flexibility for 48% of the residues, and a change in cooperativity
      occurs in 42% of residue pairs. The average distance from mutation to a site with
      a change in flexibility is 17-20 A. Interestingly, the frequency and scale of the
      changes within single point mutant structures are generally larger than those
      observed in the hen egg white lysozyme (HEWL) ortholog, which shares 61% sequence
      identity with human lysozyme. For example, point mutations often lead to
      substantial flexibility increases within the beta-subdomain, which is consistent
      with experimental results indicating that it is the nucleation site for amyloid
      formation. However, beta-subdomain flexibility within the human and HEWL
      orthologs is more similar despite the lowered sequence identity. These results
      suggest compensating mutations in HEWL reestablish desired properties.

PMID- 22396638
TI  - Degenerate T-cell recognition of peptides on MHC molecules creates large holes in
      the T-cell repertoire.
AB  - The cellular immune system screens peptides presented by host cells on MHC
      molecules to assess if the cells are infected. In this study we examined whether
      the presented peptides contain enough information for a proper self/nonself
      assessment by comparing the presented human (self) and bacterial or viral
      (nonself) peptides on a large number of MHC molecules. For all MHC molecules
      tested, only a small fraction of the presented nonself peptides from 174 species
      of bacteria and 1000 viral proteomes ([Formula: see text]0.2%) is shown to be
      identical to a presented self peptide. Next, we use available data on T-cell
      receptor-peptide-MHC interactions to estimate how well T-cells distinguish
      between similar peptides. The recognition of a peptide-MHC by the T-cell receptor
      is flexible, and as a result, about one-third of the presented nonself peptides
      is expected to be indistinguishable (by T-cells) from presented self peptides.
      This suggests that T-cells are expected to remain tolerant for a large fraction
      of the presented nonself peptides, which provides an explanation for the "holes
      in the T-cell repertoire" that are found for a large fraction of foreign
      epitopes. Additionally, this overlap with self increases the need for efficient
      self tolerance, as many self-similar nonself peptides could initiate an
      autoimmune response. Degenerate recognition of peptide-MHC-I complexes by T-cells
      thus creates large and potentially dangerous overlaps between self and nonself.

PMID- 22396639
TI  - Living on three time scales: the dynamics of plasma cell and antibody populations
      illustrated for hepatitis a virus.
AB  - Understanding the mechanisms involved in long-term persistence of humoral
      immunity after natural infection or vaccination is challenging and crucial for
      further research in immunology, vaccine development as well as health policy.
      Long-lived plasma cells, which have recently been shown to reside in survival
      niches in the bone marrow, are instrumental in the process of immunity induction
      and persistence. We developed a mathematical model, assuming two antibody
      secreting cell subpopulations (short- and long-lived plasma cells), to analyze
      the antibody kinetics after HAV-vaccination using data from two long-term follow
      up studies. Model parameters were estimated through a hierarchical nonlinear
      mixed-effects model analysis. Long-term individual predictions were derived from
      the individual empirical parameters and were used to estimate the mean time to
      immunity waning. We show that three life spans are essential to explain the
      observed antibody kinetics: that of the antibodies (around one month), the short
      lived plasma cells (several months) and the long-lived plasma cells (decades).
      Although our model is a simplified representation of the actual mechanisms that
      govern individual immune responses, the level of agreement between long-term
      individual predictions and observed kinetics is reassuringly close. The
      quantitative assessment of the time scales over which plasma cells and antibodies
      live and interact provides a basis for further quantitative research on
      immunology, with direct consequences for understanding the epidemiology of
      infectious diseases, and for timing serum sampling in clinical trials of
      vaccines.

PMID- 22396640
TI  - Indifferent, affectionate, or deceitful: lifestyles and secretomes of fungi.

PMID- 22396642
TI  - An entomopathogenic nematode by any other name.

PMID- 22396641
TI  - Phosphorylcholine allows for evasion of bactericidal antibody by Haemophilus
      influenzae.
AB  - The human pathogen Haemophilus influenzae has the ability to quickly adapt to
      different host environments through phase variation of multiple structures on its
      lipooligosaccharide (LPS), including phosphorylcholine (ChoP). During
      colonization with H. influenzae, there is a selection for ChoP+ phase variants.
      In a murine model of nasopharyngeal colonization, this selection is lost in the
      absence of adaptive immunity. Based on previous data highlighting the importance
      of natural antibody in limiting H. influenzae colonization, the effect of ChoP
      expression on antibody binding and its bactericidal activity was investigated.
      Flow cytometric analysis revealed that ChoP+ phase variants had decreased binding
      of antibody to LPS epitopes compared to ChoP- phase variants. This difference in
      antibody binding correlated with increased survival of ChoP+ phase variants in
      the presence of antibody-dependent, complement-mediated killing. ChoP+ phase
      variants were also more resistant to trypsin digestion, suggesting a general
      effect on the physical properties of the outer membrane. Moreover, ChoP-mediated
      protection against antibody binding correlated with increased resilience of outer
      membrane integrity. Collectively, these data suggest that ChoP expression
      provides a selective advantage during colonization through ChoP-mediated effects
      on the accessibility of bactericidal antibody to the cell surface.

PMID- 22396643
TI  - PK-sensitive PrP is infectious and shares basic structural features with PK
      resistant PrP.
AB  - One of the main characteristics of the transmissible isoform of the prion protein
      (PrP(Sc)) is its partial resistance to proteinase K (PK) digestion. Diagnosis of
      prion disease typically relies upon immunodetection of PK-digested PrP(Sc)
      following Western blot or ELISA. More recently, researchers determined that there
      is a sizeable fraction of PrP(Sc) that is sensitive to PK hydrolysis (sPrP(Sc)).
      Our group has previously reported a method to isolate this fraction by
      centrifugation and showed that it has protein misfolding cyclic amplification
      (PMCA) converting activity. We compared the infectivity of the sPrP(Sc) versus
      the PK-resistant (rPrP(Sc)) fractions of PrP(Sc) and analyzed the biochemical
      characteristics of these fractions under conditions of limited proteolysis. Our
      results show that sPrP(Sc) and rPrP(Sc) fractions have comparable degrees of
      infectivity and that although they contain different sized multimers, these
      multimers share similar structural properties. Furthermore, the PK-sensitive
      fractions of two hamster strains, 263K and Drowsy (Dy), showed strain-dependent
      differences in the ratios of the sPrP(Sc) to the rPrP(Sc) forms of PrP(Sc).
      Although the sPrP(Sc) and rPrP(Sc) fractions have different resistance to PK
      digestion, and have previously been shown to sediment differently, and have a
      different distribution of multimers, they share a common structure and phenotype.

PMID- 22396644
TI  - Fungal-induced cell cycle impairment, chromosome instability and apoptosis via
      differential activation of NF-kappaB.
AB  - Microbial pathogens have developed efficient strategies to compromise host immune
      responses. Cryptococcus neoformans is a facultative intracellular pathogen,
      recognised as the most common cause of systemic fungal infections leading to
      severe meningoencephalitis, mainly in immunocompromised patients. This yeast is
      characterized by a polysaccharide capsule, which inhibits its phagocytosis.
      Whereas phagocytosis escape and macrophage intracellular survival have been
      intensively studied, extracellular survival of this yeast and restraint of host
      innate immune response are still poorly understood. In this study, we have
      investigated whether C. neoformans affected macrophage cell viability and whether
      NF-kappaB (nuclear factor-kappaB), a key regulator of cell growth, apoptosis and
      inflammation, was involved. Using wild-type (WT) as well as mutant strains of C.
      neoformans for the pathogen side, and WT and mutant cell lines with altered NF
      kappaB activity or signalling as well as primary macrophages for the host side,
      we show that C. neoformans manipulated NF-kappaB-mediated signalling in a unique
      way to regulate macrophage cell fate and viability. On the one hand, serotype A
      strains reduced macrophage proliferation in a capsule-independent fashion. This
      growth decrease, which required a critical dosage of NF-kappaB activity, was
      caused by cell cycle disruption and aneuploidy, relying on fungal-induced
      modification of expression of several cell cycle checkpoint regulators in S and
      G2/M phases. On the other hand, C. neoformans infection induced macrophage
      apoptosis in a capsule-dependent manner with a differential requirement of the
      classical and alternative NF-kappaB signalling pathways, the latter one being
      essential. Together, these findings shed new light on fungal strategies to
      subvert host response through uncoupling of NF-kappaB activity in pathogen
      controlled apoptosis and impairment of cell cycle progression. They also provide
      the first demonstration of induction of aneuploidy by a fungal pathogen, which
      may have wider implications for human health as aneuploidy is proposed to promote
      tumourigenesis.

PMID- 22396645
TI  - Critical role of perforin-dependent CD8+ T cell immunity for rapid protective
      vaccination in a murine model for human smallpox.
AB  - Vaccination is highly effective in preventing various infectious diseases,
      whereas the constant threat of new emerging pathogens necessitates the
      development of innovative vaccination principles that also confer rapid
      protection in a case of emergency. Although increasing evidence points to T cell
      immunity playing a critical role in vaccination against viral diseases, vaccine
      efficacy is mostly associated with the induction of antibody responses. Here we
      analyze the immunological mechanism(s) of rapidly protective vaccinia virus
      immunization using mousepox as surrogate model for human smallpox. We found that
      fast protection against lethal systemic poxvirus disease solely depended on CD4
      and CD8 T cell responses induced by vaccination with highly attenuated modified
      vaccinia virus Ankara (MVA) or conventional vaccinia virus. Of note, CD4 T cells
      were critically required to allow for MVA induced CD8 T cell expansion and
      perforin-mediated cytotoxicity was a key mechanism of MVA induced protection. In
      contrast, selected components of the innate immune system and B cell-mediated
      responses were fully dispensable for prevention of fatal disease by immunization
      given two days before challenge. In conclusion, our data clearly demonstrate that
      perforin-dependent CD8 T cell immunity plays a key role in MVA conferred short
      term protection against lethal mousepox. Rapid induction of T cell immunity might
      serve as a new paradigm for treatments that need to fit into a scenario of
      protective emergency vaccination.

PMID- 22396646
TI  - LEDGF/p75-independent HIV-1 replication demonstrates a role for HRP-2 and remains
      sensitive to inhibition by LEDGINs.
AB  - Lens epithelium-derived growth factor (LEDGF/p75) is a cellular cofactor of HIV-1
      integrase (IN) that interacts with IN through its IN binding domain (IBD) and
      tethers the viral pre-integration complex to the host cell chromatin. Here we
      report the generation of a human somatic LEDGF/p75 knockout cell line that allows
      the study of spreading HIV-1 infection in the absence of LEDGF/p75. By homologous
      recombination the exons encoding the LEDGF/p75 IBD (exons 11 to 14) were knocked
      out. In the absence of LEDGF/p75 replication of laboratory HIV-1 strains was
      severely delayed while clinical HIV-1 isolates were replication-defective. The
      residual replication was predominantly mediated by the Hepatoma-derived growth
      factor related protein 2 (HRP-2), the only cellular protein besides LEDGF/p75
      that contains an IBD. Importantly, the recently described IN-LEDGF/p75 inhibitors
      (LEDGINs) remained active even in the absence of LEDGF/p75 by blocking the
      interaction with the IBD of HRP-2. These results further support the potential of
      LEDGINs as allosteric integrase inhibitors.

PMID- 22396647
TI  - Redundant Notch1 and Notch2 signaling is necessary for IFNgamma secretion by T
      helper 1 cells during infection with Leishmania major.
AB  - The protective immune response to intracellular parasites involves in most cases
      the differentiation of IFNgamma-secreting CD4(+) T helper (Th) 1 cells. Notch
      receptors regulate cell differentiation during development but their implication
      in the polarization of peripheral CD4(+) T helper 1 cells is not well understood.
      Of the four Notch receptors, only Notch1 (N1) and Notch2 (N2) are expressed on
      activated CD4(+) T cells. To investigate the role of Notch in Th1 cell
      differentiation following parasite infection, mice with T cell-specific gene
      ablation of N1, N2 or both (N1N2(DeltaCD4Cre)) were infected with the protozoan
      parasite Leishmania major. N1N2(DeltaCD4Cre) mice, on the C57BL/6 L. major
      resistant genetic background, developed unhealing lesions and uncontrolled
      parasitemia. Susceptibility correlated with impaired secretion of IFNgamma by
      draining lymph node CD4(+) T cells and increased secretion of the IL-5 and IL-13
      Th2 cytokines. Mice with single inactivation of N1 or N2 in their T cells were
      resistant to infection and developed a protective Th1 immune response, showing
      that CD4(+) T cell expression of N1 or N2 is redundant in driving Th1
      differentiation. Furthermore, we show that Notch signaling is required for the
      secretion of IFNgamma by Th1 cells. This effect is independent of CSL/RBP-Jkappa,
      the major effector of Notch receptors, since L. major-infected mice with a RBP
      Jkappa deletion in their T cells were able to develop IFNgamma-secreting Th1
      cells, kill parasites and heal their lesions. Collectively, we demonstrate here a
      crucial role for RBP-Jkappa-independent Notch signaling in the differentiation of
      a functional Th1 immune response following L. major infection.

PMID- 22396648
TI  - Visualization and measurement of ATP levels in living cells replicating hepatitis
      C virus genome RNA.
AB  - Adenosine 5'-triphosphate (ATP) is the primary energy currency of all living
      organisms and participates in a variety of cellular processes. Although ATP
      requirements during viral lifecycles have been examined in a number of studies, a
      method by which ATP production can be monitored in real-time, and by which ATP
      can be quantified in individual cells and subcellular compartments, is lacking,
      thereby hindering studies aimed at elucidating the precise mechanisms by which
      viral replication energized by ATP is controlled. In this study, we investigated
      the fluctuation and distribution of ATP in cells during RNA replication of the
      hepatitis C virus (HCV), a member of the Flaviviridae family. We demonstrated
      that cells involved in viral RNA replication actively consumed ATP, thereby
      reducing cytoplasmic ATP levels. Subsequently, a method to measure ATP levels at
      putative subcellular sites of HCV RNA replication in living cells was developed
      by introducing a recently-established Forster resonance energy transfer (FRET)
      based ATP indicator, called ATeam, into the NS5A coding region of the HCV
      replicon. Using this method, we were able to observe the formation of ATP
      enriched dot-like structures, which co-localize with non-structural viral
      proteins, within the cytoplasm of HCV-replicating cells but not in non
      replicating cells. The obtained FRET signals allowed us to estimate ATP
      concentrations within HCV replicating cells as ~5 mM at possible replicating
      sites and ~1 mM at peripheral sites that did not appear to be involved in HCV
      replication. In contrast, cytoplasmic ATP levels in non-replicating Huh-7 cells
      were estimated as ~2 mM. To our knowledge, this is the first study to demonstrate
      changes in ATP concentration within cells during replication of the HCV genome
      and increased ATP levels at distinct sites within replicating cells. ATeam may be
      a powerful tool for the study of energy metabolism during replication of the
      viral genome.

PMID- 22396650
TI  - Short ORF-dependent ribosome shunting operates in an RNA picorna-like virus and a
      DNA pararetrovirus that cause rice tungro disease.
AB  - Rice tungro disease is caused by synergistic interaction of an RNA picorna-like
      virus Rice tungro spherical virus (RTSV) and a DNA pararetrovirus Rice tungro
      bacilliform virus (RTBV). It is spread by insects owing to an RTSV-encoded
      transmission factor. RTBV has evolved a ribosome shunt mechanism to initiate
      translation of its pregenomic RNA having a long and highly structured leader. We
      found that a long leader of RTSV genomic RNA remarkably resembles the RTBV
      leader: both contain several short ORFs (sORFs) and potentially fold into a large
      stem-loop structure with the first sORF terminating in front of the stem basal
      helix. Using translation assays in rice protoplasts and wheat germ extracts, we
      show that, like in RTBV, both initiation and proper termination of the first sORF
      translation in front of the stem are required for shunt-mediated translation of a
      reporter ORF placed downstream of the RTSV leader. The base pairing that forms
      the basal helix is required for shunting, but its sequence can be varied. Shunt
      efficiency in RTSV is lower than in RTBV. But in addition to shunting the RTSV
      leader sequence allows relatively efficient linear ribosome migration, which also
      contributes to translation initiation downstream of the leader. We conclude that
      RTSV and RTBV have developed a similar, sORF-dependent shunt mechanism possibly
      to adapt to the host translation system and/or coordinate their life cycles.
      Given that sORF-dependent shunting also operates in a pararetrovirus Cauliflower
      mosaic virus and likely in other pararetroviruses that possess a conserved shunt
      configuration in their leaders it is tempting to propose that RTSV may have
      acquired shunt cis-elements from RTBV during their co-existence.

PMID- 22396649
TI  - Kaposi's sarcoma herpesvirus upregulates Aurora A expression to promote p53
      phosphorylation and ubiquitylation.
AB  - Aberrant expression of Aurora A kinase has been frequently implicated in many
      cancers and contributes to chromosome instability and phosphorylation-mediated
      ubiquitylation and degradation of p53 for tumorigenesis. Previous studies showed
      that p53 is degraded by Kaposi's sarcoma herpesvirus (KSHV) encoded latency
      associated nuclear antigen (LANA) through its SOCS-box (suppressor of cytokine
      signaling, LANA(SOCS)) motif-mediated recruitment of the EC(5)S ubiquitin
      complex. Here we demonstrate that Aurora A transcriptional expression is
      upregulated by LANA and markedly elevated in both Kaposi's sarcoma tissue and
      human primary cells infected with KSHV. Moreover, reintroduction of Aurora A
      dramatically enhances the binding affinity of p53 with LANA and LANA(SOCS)
      mediated ubiquitylation of p53 which requires phosphorylation on Ser215 and
      Ser315. Small hairpin RNA or a dominant negative mutant of Aurora A kinase
      efficiently disrupts LANA-induced p53 ubiquitylation and degradation, and leads
      to induction of p53 transcriptional and apoptotic activities. These studies
      provide new insights into the mechanisms by which LANA can upregulate expression
      of a cellular oncogene and simultaneously destabilize the activities of the p53
      tumor suppressor in KSHV-associated human cancers.

PMID- 22396651
TI  - Influenza virus respiratory infection and transmission following ocular
      inoculation in ferrets.
AB  - While influenza viruses are a common respiratory pathogen, sporadic reports of
      conjunctivitis following human infection demonstrates the ability of this virus
      to cause disease outside of the respiratory tract. The ocular surface represents
      both a potential site of virus replication and a portal of entry for
      establishment of a respiratory infection. However, the properties which govern
      ocular tropism of influenza viruses, the mechanisms of virus spread from ocular
      to respiratory tissue, and the potential differences in respiratory disease
      initiated from different exposure routes are poorly understood. Here, we
      established a ferret model of ocular inoculation to explore the development of
      virus pathogenicity and transmissibility following influenza virus exposure by
      the ocular route. We found that multiple subtypes of human and avian influenza
      viruses mounted a productive virus infection in the upper respiratory tract of
      ferrets following ocular inoculation, and were additionally detected in ocular
      tissue during the acute phase of infection. H5N1 viruses maintained their ability
      for systemic spread and lethal infection following inoculation by the ocular
      route. Replication-independent deposition of virus inoculum from ocular to
      respiratory tissue was limited to the nares and upper trachea, unlike traditional
      intranasal inoculation which results in virus deposition in both upper and lower
      respiratory tract tissues. Despite high titers of replicating transmissible
      seasonal viruses in the upper respiratory tract of ferrets inoculated by the
      ocular route, virus transmissibility to naive contacts by respiratory droplets
      was reduced following ocular inoculation. These data improve our understanding of
      the mechanisms of virus spread following ocular exposure and highlight
      differences in the establishment of respiratory disease and virus
      transmissibility following use of different inoculation volumes and routes.

PMID- 22396653
TI  - REST-mediated recruitment of polycomb repressor complexes in mammalian cells.
AB  - Polycomb Repressive Complex (PRC) 1 and PRC2 regulate genes involved in
      differentiation and development. However, the mechanism for how PRC1 and PRC2 are
      recruited to genes in mammalian cells is unclear. Here we present evidence for an
      interaction between the transcription factor REST, PRC1, and PRC2 and show that
      RNF2 and REST co-regulate a number of neuronal genes in human teratocarcinoma
      cells (NT2-D1). Using NT2-D1 cells as a model of neuronal differentiation, we
      furthermore showed that retinoic-acid stimulation led to displacement of PRC1 at
      REST binding sites, reduced H3K27Me3, and increased gene expression. Genome-wide
      analysis of Polycomb binding in Rest-/- and Eed-/- mouse embryonic stem (mES)
      cells showed that Rest was required for PRC1 recruitment to a subset of Polycomb
      regulated neuronal genes. Furthermore, we found that PRC1 can be recruited to
      Rest binding sites independently of CpG islands and the H3K27Me3 mark.
      Surprisingly, PRC2 was frequently increased around Rest binding sites located in
      CpG-rich regions in the Rest-/- mES cells, indicating a more complex interplay
      where Rest also can limit PRC2 recruitment. Therefore, we propose that Rest has
      context-dependent functions for PRC1- and PRC2- recruitment, which allows this
      transcription factor to act both as a recruiter of Polycomb as well as a limiting
      factor for PRC2 recruitment at CpG islands.

PMID- 22396652
TI  - A20 (Tnfaip3) deficiency in myeloid cells protects against influenza A virus
      infection.
AB  - The innate immune response provides the first line of defense against viruses and
      other pathogens by responding to specific microbial molecules. Influenza A virus
      (IAV) produces double-stranded RNA as an intermediate during the replication life
      cycle, which activates the intracellular pathogen recognition receptor RIG-I and
      induces the production of proinflammatory cytokines and antiviral interferon.
      Understanding the mechanisms that regulate innate immune responses to IAV and
      other viruses is of key importance to develop novel therapeutic strategies. Here
      we used myeloid cell specific A20 knockout mice to examine the role of the
      ubiquitin-editing protein A20 in the response of myeloid cells to IAV infection.
      A20 deficient macrophages were hyperresponsive to double stranded RNA and IAV
      infection, as illustrated by enhanced NF-kappaB and IRF3 activation, concomitant
      with increased production of proinflammatory cytokines, chemokines and type I
      interferon. In vivo this was associated with an increased number of alveolar
      macrophages and neutrophils in the lungs of IAV infected mice. Surprisingly,
      myeloid cell specific A20 knockout mice are protected against lethal IAV
      infection. These results challenge the general belief that an excessive host
      proinflammatory response is associated with IAV-induced lethality, and suggest
      that under certain conditions inhibition of A20 might be of interest in the
      management of IAV infections.

PMID- 22396654
TI  - Insulin/IGF-1 and hypoxia signaling act in concert to regulate iron homeostasis
      in Caenorhabditis elegans.
AB  - Iron plays an essential role in many biological processes, but also catalyzes the
      formation of reactive oxygen species (ROS), which can cause molecular damage.
      Iron homeostasis is therefore a critical determinant of fitness. In
      Caenorhabditis elegans, insulin/IGF-1 signaling (IIS) promotes growth and
      reproduction but limits stress resistance and lifespan through inactivation of
      the DAF-16/FoxO transcription factor (TF). We report that long-lived daf-2
      insulin/IGF-1 receptor mutants show a daf-16-dependent increase in expression of
      ftn-1, which encodes the iron storage protein H-ferritin. To better understand
      the regulation of iron homeostasis, we performed a TF-limited genetic screen for
      factors influencing ftn-1 gene expression. The screen identified the heat-shock
      TF hsf-1, the MAD bHLH TF mdl-1, and the putative histone acetyl transferase ada
      2 as activators of ftn-1 expression. It also revealed that the HIFalpha homolog
      hif-1 and its binding partner aha-1 (HIFbeta) are potent repressors of ftn-1
      expression. ftn-1 expression is induced by exposure to iron, and we found that
      hif-1 was required for this induction. In addition, we found that the prolyl
      hydroxylase EGL-9, which represses HIF-1 via the von Hippel-Lindau tumor
      suppressor VHL-1, can also act antagonistically to VHL-1 in regulating ftn-1.
      This suggests a novel mechanism for HIF target gene regulation by these
      evolutionarily conserved and clinically important hydroxylases. Our findings
      imply that the IIS and HIF pathways act together to regulate iron homeostasis in
      C. elegans. We suggest that IIS/DAF-16 regulation of ftn-1 modulates a trade-off
      between growth and stress resistance, as elevated iron availability supports
      growth but also increases ROS production.

PMID- 22396655
TI  - Genomic tools for evolution and conservation in the chimpanzee: Pan troglodytes
      ellioti is a genetically distinct population.
AB  - In spite of its evolutionary significance and conservation importance, the
      population structure of the common chimpanzee, Pan troglodytes, is still poorly
      understood. An issue of particular controversy is whether the proposed fourth
      subspecies of chimpanzee, Pan troglodytes ellioti, from parts of Nigeria and
      Cameroon, is genetically distinct. Although modern high-throughput SNP genotyping
      has had a major impact on our understanding of human population structure and
      demographic history, its application to ecological, demographic, or conservation
      questions in non-human species has been extremely limited. Here we apply these
      tools to chimpanzee population structure, using ~700 autosomal SNPs derived from
      chimpanzee genomic data and a further ~100 SNPs from targeted re-sequencing. We
      demonstrate conclusively the existence of P. t. ellioti as a genetically distinct
      subgroup. We show that there is clear differentiation between the verus,
      troglodytes, and ellioti populations at the SNP and haplotype level, on a scale
      that is greater than that separating continental human populations. Further, we
      show that only a small set of SNPs (10-20) is needed to successfully assign
      individuals to these populations. Tellingly, use of only mitochondrial DNA
      variation to classify individuals is erroneous in 4 of 54 cases, reinforcing the
      dangers of basing demographic inference on a single locus and implying that the
      demographic history of the species is more complicated than that suggested
      analyses based solely on mtDNA. In this study we demonstrate the feasibility of
      developing economical and robust tests of individual chimpanzee origin as well as
      in-depth studies of population structure. These findings have important
      implications for conservation strategies and our understanding of the evolution
      of chimpanzees. They also act as a proof-of-principle for the use of cheap high
      throughput genomic methods for ecological questions.

PMID- 22396656
TI  - MNS1 is essential for spermiogenesis and motile ciliary functions in mice.
AB  - During spermiogenesis, haploid round spermatids undergo dramatic cell
      differentiation and morphogenesis to give rise to mature spermatozoa for
      fertilization, including nuclear elongation, chromatin remodeling, acrosome
      formation, and development of flagella. The molecular mechanisms underlining
      these fundamental processes remain poorly understood. Here, we report that MNS1,
      a coiled-coil protein of unknown function, is essential for spermiogenesis. We
      find that MNS1 is expressed in the germ cells in the testes and localizes to
      sperm flagella in a detergent-resistant manner, indicating that it is an integral
      component of flagella. MNS1-deficient males are sterile, as they exhibit a sharp
      reduction in sperm production and the remnant sperm are immotile with abnormal
      short tails. In MNS1-deficient sperm flagella, the characteristic arrangement of
      "9+2" microtubules and outer dense fibers are completely disrupted. In addition,
      MNS1-deficient mice display situs inversus and hydrocephalus. MNS1-deficient
      tracheal motile cilia lack some outer dynein arms in the axoneme. Moreover, MNS1
      monomers interact with each other and are able to form polymers in cultured
      somatic cells. These results demonstrate that MNS1 is essential for
      spermiogenesis, the assembly of sperm flagella, and motile ciliary functions.

PMID- 22396657
TI  - Parkinson's disease-associated kinase PINK1 regulates Miro protein level and
      axonal transport of mitochondria.
AB  - Mutations in Pten-induced kinase 1 (PINK1) are linked to early-onset familial
      Parkinson's disease (FPD). PINK1 has previously been implicated in mitochondrial
      fission/fusion dynamics, quality control, and electron transport chain function.
      However, it is not clear how these processes are interconnected and whether they
      are sufficient to explain all aspects of PINK1 pathogenesis. Here we show that
      PINK1 also controls mitochondrial motility. In Drosophila, downregulation of
      dMiro or other components of the mitochondrial transport machinery rescued dPINK1
      mutant phenotypes in the muscle and dopaminergic (DA) neurons, whereas dMiro
      overexpression alone caused DA neuron loss. dMiro protein level was increased in
      dPINK1 mutant but decreased in dPINK1 or dParkin overexpression conditions. In
      Drosophila larval motor neurons, overexpression of dPINK1 inhibited axonal
      mitochondria transport in both anterograde and retrograde directions, whereas
      dPINK1 knockdown promoted anterograde transport. In HeLa cells, overexpressed
      hPINK1 worked together with hParkin, another FPD gene, to regulate the
      ubiquitination and degradation of hMiro1 and hMiro2, apparently in a Ser-156
      phosphorylation-independent manner. Also in HeLa cells, loss of hMiro promoted
      the perinuclear clustering of mitochondria and facilitated autophagy of damaged
      mitochondria, effects previously associated with activation of the PINK1/Parkin
      pathway. These newly identified functions of PINK1/Parkin and Miro in
      mitochondrial transport and mitophagy contribute to our understanding of the
      complex interplays in mitochondrial quality control that are critically involved
      in PD pathogenesis, and they may explain the peripheral neuropathy symptoms seen
      in some PD patients carrying particular PINK1 or Parkin mutations. Moreover, the
      different effects of loss of PINK1 function on Miro protein level in Drosophila
      and mouse cells may offer one explanation of the distinct phenotypic
      manifestations of PINK1 mutants in these two species.

PMID- 22396658
TI  - Rapid analysis of Saccharomyces cerevisiae genome rearrangements by multiplex
      ligation-dependent probe amplification.
AB  - Aneuploidy and gross chromosomal rearrangements (GCRs) can lead to genetic
      diseases and the development of cancer. We previously demonstrated that
      introduction of the repetitive retrotransposon Ty912 onto a nonessential
      chromosome arm of Saccharomyces cerevisiae led to increased genome instability
      predominantly due to increased rates of formation of monocentric nonreciprocal
      translocations. In this study, we adapted Multiplex Ligation-dependent Probe
      Amplification (MLPA) to analyze a large numbers of these GCRs. Using MLPA, we
      found that the distribution of translocations induced by the presence of Ty912 in
      a wild-type strain was nonrandom and that the majority of these translocations
      were mediated by only six translocation targets on four different chromosomes,
      even though there were 254 potential Ty-related translocation targets in the S.
      cerevisiae genome. While the majority of Ty912-mediated translocations resulted
      from RAD52-dependent recombination, we observed a number of nonreciprocal
      translocations mediated by RAD52-independent recombination between Ty1 elements.
      The formation of these RAD52-independent translocations did not require the Rad51
      or Rad59 homologous pairing proteins or the Rad1-Rad10 endonuclease complex that
      processes branched DNAs during recombination. Finally, we found that defects in
      ASF1-RTT109-dependent acetylation of histone H3 lysine residue 56 (H3K56)
      resulted in increased accumulation of both GCRs and whole-chromosome
      duplications, and resulted in aneuploidy that tended to occur simultaneously with
      GCRs. Overall, we found that MLPA is a versatile technique for the rapid analysis
      of GCRs and can facilitate the genetic analysis of the pathways that prevent and
      promote GCRs and aneuploidy.

PMID- 22396660
TI  - A genome-wide association study of nephrolithiasis in the Japanese population
      identifies novel susceptible Loci at 5q35.3, 7p14.3, and 13q14.1.
AB  - Nephrolithiasis is a common nephrologic disorder with complex etiology. To
      identify the genetic factor(s) for nephrolithiasis, we conducted a three-stage
      genome-wide association study (GWAS) using a total of 5,892 nephrolithiasis cases
      and 17,809 controls of Japanese origin. Here we found three novel loci for
      nephrolithiasis: RGS14-SLC34A1-PFN3-F12 on 5q35.3 (rs11746443; P = 8.51*10-12,
      odds ratio (OR) = 1.19), INMT-FAM188B-AQP1 on 7p14.3 (rs1000597; P = 2.16*10-14,
      OR = 1.22), and DGKH on 13q14.1 (rs4142110; P = 4.62*10-9, OR = 1.14). Subsequent
      analyses in 21,842 Japanese subjects revealed the association of SNP rs11746443
      with the reduction of estimated glomerular filtration rate (eGFR) (P = 6.54*10
      8), suggesting a crucial role for this variation in renal function. Our findings
      elucidated the significance of genetic variations for the pathogenesis of
      nephrolithiasis.

PMID- 22396659
TI  - A downstream CpG island controls transcript initiation and elongation and the
      methylation state of the imprinted Airn macro ncRNA promoter.
AB  - A CpG island (CGI) lies at the 5' end of the Airn macro non-protein-coding (nc)
      RNA that represses the flanking Igf2r promoter in cis on paternally inherited
      chromosomes. In addition to being modified on maternally inherited chromosomes by
      a DNA methylation imprint, the Airn CGI shows two unusual organization features:
      its position immediately downstream of the Airn promoter and transcription start
      site and a series of tandem direct repeats (TDRs) occupying its second half. The
      physical separation of the Airn promoter from the CGI provides a model to
      investigate if the CGI plays distinct transcriptional and epigenetic roles. We
      used homologous recombination to generate embryonic stem cells carrying deletions
      at the endogenous locus of the entire CGI or just the TDRs. The deleted Airn
      alleles were analyzed by using an ES cell imprinting model that recapitulates the
      onset of Igf2r imprinted expression in embryonic development or by using knock
      out mice. The results show that the CGI is required for efficient Airn initiation
      and to maintain the unmethylated state of the Airn promoter, which are both
      necessary for Igf2r repression on the paternal chromosome. The TDRs occupying the
      second half of the CGI play a minor role in Airn transcriptional elongation or
      processivity, but are essential for methylation on the maternal Airn promoter
      that is necessary for Igf2r to be expressed from this chromosome. Together the
      data indicate the existence of a class of regulatory CGIs in the mammalian genome
      that act downstream of the promoter and transcription start.

PMID- 22396661
TI  - Modelling human regulatory variation in mouse: finding the function in genome
      wide association studies and whole-genome sequencing.
AB  - An increasing body of literature from genome-wide association studies and human
      whole-genome sequencing highlights the identification of large numbers of
      candidate regulatory variants of potential therapeutic interest in numerous
      diseases. Our relatively poor understanding of the functions of non-coding
      genomic sequence, and the slow and laborious process of experimental validation
      of the functional significance of human regulatory variants, limits our ability
      to fully benefit from this information in our efforts to comprehend human
      disease. Humanized mouse models (HuMMs), in which human genes are introduced into
      the mouse, suggest an approach to this problem. In the past, HuMMs have been used
      successfully to study human disease variants; e.g., the complex genetic condition
      arising from Down syndrome, common monogenic disorders such as Huntington disease
      and beta-thalassemia, and cancer susceptibility genes such as BRCA1. In this
      commentary, we highlight a novel method for high-throughput single-copy site
      specific generation of HuMMs entitled High-throughput Human Genes on the X
      Chromosome (HuGX). This method can be applied to most human genes for which a
      bacterial artificial chromosome (BAC) construct can be derived and a mouse-null
      allele exists. This strategy comprises (1) the use of recombineering technology
      to create a human variant-harbouring BAC, (2) knock-in of this BAC into the mouse
      genome using Hprt docking technology, and (3) allele comparison by interspecies
      complementation. We demonstrate the throughput of the HuGX method by generating a
      series of seven different alleles for the human NR2E1 gene at Hprt. In future
      challenges, we consider the current limitations of experimental approaches and
      call for a concerted effort by the genetics community, for both human and mouse,
      to solve the challenge of the functional analysis of human regulatory variation.

PMID- 22396662
TI  - Genetic basis of hidden phenotypic variation revealed by increased translational
      readthrough in yeast.
AB  - Eukaryotic release factors 1 and 3, encoded by SUP45 and SUP35, respectively, in
      Saccharomyces cerevisiae, are required for translation termination. Recent
      studies have shown that, besides these two key factors, several genetic and
      epigenetic mechanisms modulate the efficiency of translation termination. These
      mechanisms, through modifying translation termination fidelity, were shown to
      affect various cellular processes, such as mRNA degradation, and in some cases
      could confer a beneficial phenotype to the cell. The most studied example of such
      a mechanism is [PSI+], the prion conformation of Sup35p, which can have
      pleiotropic effects on growth that vary among different yeast strains. However,
      genetic loci underlying such readthrough-dependent, background-specific
      phenotypes have yet to be identified. Here, we used sup35(C653R), a partial loss
      of-function allele of the SUP35 previously shown to increase readthrough of stop
      codons and recapitulate some [PSI+]-dependent phenotypes, to study the genetic
      basis of phenotypes revealed by increased translational readthrough in two
      divergent yeast strains: BY4724 (a laboratory strain) and RM11_1a (a wine
      strain). We first identified growth conditions in which increased readthrough of
      stop codons by sup35(C653R) resulted in different growth responses between these
      two strains. We then used a recently developed linkage mapping technique, extreme
      QTL mapping (X-QTL), to identify readthrough-dependent loci for the observed
      growth differences. We further showed that variation in SKY1, an SR protein
      kinase, underlies a readthrough-dependent locus observed for growth on diamide
      and hydrogen peroxide. We found that the allelic state of SKY1 interacts with
      readthrough level and the genetic background to determine growth rate in these
      two conditions.

PMID- 22396663
TI  - Akirin links twist-regulated transcription with the Brahma chromatin remodeling
      complex during embryogenesis.
AB  - The activities of developmentally critical transcription factors are regulated
      via interactions with cofactors. Such interactions influence transcription factor
      activity either directly through protein-protein interactions or indirectly by
      altering the local chromatin environment. Using a yeast double-interaction
      screen, we identified a highly conserved nuclear protein, Akirin, as a novel
      cofactor of the key Drosophila melanogaster mesoderm and muscle transcription
      factor Twist. We find that Akirin interacts genetically and physically with Twist
      to facilitate expression of some, but not all, Twist-regulated genes during
      embryonic myogenesis. akirin mutant embryos have muscle defects consistent with
      altered regulation of a subset of Twist-regulated genes. To regulate
      transcription, Akirin colocalizes and genetically interacts with subunits of the
      Brahma SWI/SNF-class chromatin remodeling complex. Our results suggest that,
      mechanistically, Akirin mediates a novel connection between Twist and a chromatin
      remodeling complex to facilitate changes in the chromatin environment, leading to
      the optimal expression of some Twist-regulated genes during Drosophila
      myogenesis. We propose that this Akirin-mediated link between transcription
      factors and the Brahma complex represents a novel paradigm for providing tissue
      and target specificity for transcription factor interactions with the chromatin
      remodeling machinery.

PMID- 22396664
TI  - Cell size and the initiation of DNA replication in bacteria.
AB  - In eukaryotes, DNA replication is coupled to the cell cycle through the actions
      of cyclin-dependent kinases and associated factors. In bacteria, the prevailing
      view, based primarily from work in Escherichia coli, is that growth-dependent
      accumulation of the highly conserved initiator, DnaA, triggers initiation.
      However, the timing of initiation is unchanged in Bacillus subtilis mutants that
      are ~30% smaller than wild-type cells, indicating that achievement of a
      particular cell size is not obligatory for initiation. Prompted by this finding,
      we re-examined the link between cell size and initiation in both E. coli and B.
      subtilis. Although changes in DNA replication have been shown to alter both E.
      coli and B. subtilis cell size, the converse (the effect of cell size on DNA
      replication) has not been explored. Here, we report that the mechanisms
      responsible for coordinating DNA replication with cell size vary between these
      two model organisms. In contrast to B. subtilis, small E. coli mutants delayed
      replication initiation until they achieved the size at which wild-type cells
      initiate. Modest increases in DnaA alleviated the delay, supporting the view that
      growth-dependent accumulation of DnaA is the trigger for replication initiation
      in E. coli. Significantly, although small E. coli and B. subtilis cells both
      maintained wild-type concentration of DnaA, only the E. coli mutants failed to
      initiate on time. Thus, rather than the concentration, the total amount of DnaA
      appears to be more important for initiation timing in E. coli. The difference in
      behavior of the two bacteria appears to lie in the mechanisms that control the
      activity of DnaA.

PMID- 22396665
TI  - Interpreting meta-analyses of genome-wide association studies.
AB  - Meta-analysis is an increasingly popular tool for combining multiple genome-wide
      association studies in a single analysis to identify associations with small
      effect sizes. The effect sizes between studies in a meta-analysis may differ and
      these differences, or heterogeneity, can be caused by many factors. If
      heterogeneity is observed in the results of a meta-analysis, interpreting the
      cause of heterogeneity is important because the correct interpretation can lead
      to a better understanding of the disease and a more effective design of a
      replication study. However, interpreting heterogeneous results is difficult. The
      standard approach of examining the association p-values of the studies does not
      effectively predict if the effect exists in each study. In this paper, we propose
      a framework facilitating the interpretation of the results of a meta-analysis.
      Our framework is based on a new statistic representing the posterior probability
      that the effect exists in each study, which is estimated utilizing cross-study
      information. Simulations and application to the real data show that our framework
      can effectively segregate the studies predicted to have an effect, the studies
      predicted to not have an effect, and the ambiguous studies that are underpowered.
      In addition to helping interpretation, the new framework also allows us to
      develop a new association testing procedure taking into account the existence of
      effect.

PMID- 22396666
TI  - DNA damage in Nijmegen Breakage Syndrome cells leads to PARP hyperactivation and
      increased oxidative stress.
AB  - Nijmegen Breakage Syndrome (NBS), an autosomal recessive genetic instability
      syndrome, is caused by hypomorphic mutation of the NBN gene, which codes for the
      protein nibrin. Nibrin is an integral member of the MRE11/RAD50/NBN (MRN) complex
      essential for processing DNA double-strand breaks. Cardinal features of NBS are
      immunodeficiency and an extremely high incidence of hematological malignancies.
      Recent studies in conditional null mutant mice have indicated disturbances in
      redox homeostasis due to impaired DSB processing. Clearly this could contribute
      to DNA damage, chromosomal instability, and cancer occurrence. Here we show, in
      the complete absence of nibrin in null mutant mouse cells, high levels of
      reactive oxygen species several hours after exposure to a mutagen. We show
      further that NBS patient cells, which unlike mouse null mutant cells have a
      truncated nibrin protein, also have high levels of reactive oxygen after DNA
      damage and that this increased oxidative stress is caused by depletion of NAD+
      due to hyperactivation of the strand-break sensor, Poly(ADP-ribose) polymerase.
      Both hyperactivation of Poly(ADP-ribose) polymerase and increased ROS levels were
      reversed by use of a specific Poly(ADP-ribose) polymerase inhibitor. The
      extremely high incidence of malignancy among NBS patients is the result of the
      combination of a primary DSB repair deficiency with secondary oxidative DNA
      damage.

PMID- 22396667
TI  - Genomic analysis of the hydrocarbon-producing, cellulolytic, endophytic fungus
      Ascocoryne sarcoides.
AB  - The microbial conversion of solid cellulosic biomass to liquid biofuels may
      provide a renewable energy source for transportation fuels. Endophytes represent
      a promising group of organisms, as they are a mostly untapped reservoir of
      metabolic diversity. They are often able to degrade cellulose, and they can
      produce an extraordinary diversity of metabolites. The filamentous fungal
      endophyte Ascocoryne sarcoides was shown to produce potential-biofuel metabolites
      when grown on a cellulose-based medium; however, the genetic pathways needed for
      this production are unknown and the lack of genetic tools makes traditional
      reverse genetics difficult. We present the genomic characterization of A.
      sarcoides and use transcriptomic and metabolomic data to describe the genes
      involved in cellulose degradation and to provide hypotheses for the biofuel
      production pathways. In total, almost 80 biosynthetic clusters were identified,
      including several previously found only in plants. Additionally, many
      transcriptionally active regions outside of genes showed condition-specific
      expression, offering more evidence for the role of long non-coding RNA in gene
      regulation. This is one of the highest quality fungal genomes and, to our
      knowledge, the only thoroughly annotated and transcriptionally profiled fungal
      endophyte genome currently available. The analyses and datasets contribute to the
      study of cellulose degradation and biofuel production and provide the genomic
      foundation for the study of a model endophyte system.

PMID- 22396668
TI  - Epidemiological analysis of burn patients in the military hospital, Rabat,
      Morocco.
AB  - A retrospective study was conducted of burn patients admitted to the military
      hospital in Rabat, Morocco, in the 6-yr period from 2004 to 2009. This is the
      first multivariate study to be performed in Morocco. The epidemiological data
      from the 291 patients hospitalized were collected and studied. The type of burn
      was indicated in 284 of the patients: 94% of the injuries were thermal burns, 4%
      were electrical burns, and 1.5% chemical burns. In 261 cases the exact aetiology
      was noted: 56% of accidents were caused by flames, 38% by hot liquids, 4% by
      electric current, and 2% by chemicals. The distribution of the Moroccan
      population is as follows: 0-4 yr, 7%; 5-l4 yr, 8%; 15-19 yr, 8%; 20-59 yr, 70%;
      over 60 yr, 7%. The male/female sex ratio was 1.63. The mean duration of
      hospitalization stay was 42 +/- 62 days. The mean body surface area burned was 21
      +/- 18%. Total mortality was 5%; 57% of deaths were due to septic shock. Our
      results were similar to data from other studies in the literature, with certain
      characteristics in our series, especially the age bracket most affected, the body
      surface area burned, and the mechanisms of injury.

PMID- 22396669
TI  - Epidemiology of ventilator-associated tracheobronchitis and vantilator-associated
      pneumonia in patients with inhalation injury at the Burn Centre in Brno (Czech
      Republic).
AB  - Aim. The aim of this work is to determine the incidence of ventilator-associated
      tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) and to define
      the define the most important respiratory pathogens in patients with inhalation
      injury. Introduction. Infectious complications in severely burned patients
      present serious problems. Patients with inhalation injuries are exposed to
      greater risk owing to the possible development of infectious complications in the
      lower respiratory tract. VAP is the predominant cause of death in these patients.
      This is due to the increasing resistance of strains of Gram-negative bacteria
      such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella
      pneumoniae. Design. Retrospective, monocentric. Setting. A five-bed burn
      intensive care unit. Material and methods. Between 2004 and 2009, 348 adult
      patients were hospitalized in the intensive care unit of the Department of Burns
      and Reconstructive Surgery, Brno University Hospital, Czech Republic. Of these,
      127 (36.49%) were diagnosed by bronchoscopy as having inhalation injury. The
      prerequisite for inclusion in the cohort was an inhalation injury requiring
      artificial ventilation for at least 48 h. The lower airway microbiological
      condition was monitored regularly by sampling biological material for cultures
      (sputum, tracheobronchial aspirates, etc.). For the diagnosis of VAP and VAT we
      used the Centers for Disease Control and Prevention criteria and the Clinical
      Pulmonary Infection Score. Results. The average age of the 127 patients (31
      women/96 men) included in the study was 38.4 yr (range, 21-69 yr) and the average
      total body surface area (TBSA) burned was 29.3% (range, 2-75%). The average
      length of hospital stay was 49.4 days (range, 4-150 days) and the duration of
      mechanical ventilation 8.7 days; 18 patients (14.2%) died. In patients with
      inhalation injury, 309 strains of bacteria were cultivated from the lower
      respiratory tract, of which 234 were Gram-negative. All of these bacterial
      strains were isolated in significant quantities for lower respiratory tract
      infection. The most common bacteria isolated from the lower respiratory tract was
      Klebsiella pneumoniae (78 times), followed by Pseudomonas aeruginosa (49x), and
      Acinetobacter baumannii (28x). VAT was diagnosed in 109 patients (85.8%) in the
      cohort. The incidence of VAT was calculated to be 98.8 per 1000 days of
      mechanical ventilation. VAP was diagnosed in 34 patients in the cohort (26.8%).
      The incidence of VAP was calculated as being 30.8 cases per 1,000 days of
      mechanical ventilation. In eight patients (23.5%), VAP was diagnosed within 5
      days of initiation of mechanical ventilation (early onset) and in 26 patients
      (76.5%) after a longer period (late onset). The most common aetiological agent of
      VAT and VAP was Klebsiella pneumoniae (respectively 41.3% and 35.3%). Conclusion.
      In this study we were able to determine the incidence of VAP and VAT in patients
      with inhalation injury. In spite of the advances in diagnostics and therapy,
      inhalation injury is still burdened with disappointingly high morbidity and
      mortality rates. For this reason, the treatment of VAP remains a major challenge
      for all physicians caring for patients with inhalation injury.

PMID- 22396670
TI  - [Pharmaceutical analysis of antibiotic drug prescription in the burns and plastic
      surgery departiment of the Mohammed Military Teaching Hospital].
AB  - Infection has long been the main cause of mortality in severely burned patients.
      The aim of this work is to assess the prescription of antibiotics in our Burns
      and Plastic Surgery Department in relation to the recommendations of the
      manufacturers. A summary is provided of the specific features of these products.
      Patients hospitalized in the Mohammed V Military Teaching Hospital, Rabat,
      Morocco, during the period January 2008/May 2009 and treated with antibiotics
      were considered. This retrospective study concerned 227 nominal medical
      prescriptions of antibiotics to 41 patients: 70% of the prescriptions were
      nondocumented. The commonest method of administration was by injection (89%).
      Various groups of therapeutic drugs were used: betalactamines (65%),
      glycopeptides (10.5%), aminosides (9%), quinolones (7%), and colistin (4.3%),
      plus 4.2% from other groups (metronidazole 500 mg, perfusion; fluconazol 100
      mg/50 ml, injection; rifampicin 600 mg, perfusion; silver sulphadiazine, 2%
      fusidic acid cream). A total of 227 nominal medical prescriptions were analysed:
      the dosages and counter-indications were correctly respected. Three drug
      interactions were recorded (fluconazol-rifampicin, fluconazol-Saccharomyces
      boulardii, amikacin-vancomycin). This study shows the importance of the
      pharmaceutical analysis of prescriptions for antibiotics used in a burns unit,
      which are active but therefore very toxic.

PMID- 22396671
TI  - Comparison between topical honey and mafenide acetate in treatment of burn
      wounds.
AB  - Histological and clinical studies of wound healing were performed in comparable
      cases of fresh partial-thickness burns treated with honey dressing or mafenide
      acetate in two groups of 50 randomly allocated patients. Of the patients with
      honey-treated wounds, 84% showed satisfactory epithelialization by day 7 and 100%
      by day 21. In wounds treated with mafenide acetate, epithelialization occurred by
      day 7 in 72% of cases and in 84% by day 21. Histological evidence of reparative
      activity was observed in 80% of wounds treated with honey dressing by day 7 with
      minimal inflammation. Fifty-two per cent of the mafenide acetate treated wounds
      showed reparative activity with inflammatory changes by day 7. Reparative
      activity reached 100% by day 21 with the honey dressing and 84% with mafenide
      acetate. Thus, in honey-dressed wounds, early subsidence of acute inflammatory
      changes, better control of infection, and quicker wound healing were observed,
      while in mafenide acetate treated wounds a sustained inflammatory reaction was
      noted even on epithelialization.

PMID- 22396672
TI  - Acid burn violence in Iran.
AB  - Background. Acid assault is one of the most brutal of crimes. This crime is not
      meant to kill but to punish the victim or to destroy the victim's social life.
      This violent act usually occurs in third-world countries. The aim of this paper
      is to assess the epidemiological factors that steer a person toward such a
      violent act. Method. From May 2004 to October 2010, the charts of victims of acid
      violence referred to the Motahari Burn Center in Iran were reviewed. During this
      6-yr period, 59 patients were included in this retrospective study. We identified
      the aetiology and the extent of the damage that was produced as a result of
      throwing corrosive chemicals onto the victim's body for the purpose of revenge.
      Results. The cases reviewed concerned 51% male patients and 49% female. The face
      and upper body were the most commonly injured areas, and the most common
      assailant was a close family member. Conclusion. The authors believe that lack of
      information about the catastrophic outcome of this action, plus the widespread
      availability of strong, destructive chemicals, are the main reasons for the
      rising incidence of this crime.

PMID- 22396673
TI  - An unusual burn caused by hot argy wormwood leaf water.
AB  - An unusual burn case caused by hot wormwood leaf water is discussed. A 29-yr-old
      woman sustained a 7% seconddegree burn on both buttocks and the left thigh. This
      case report highlights a rare cause of chemical burn that may become more common
      with increasing use of this method of traditional Chinese medicine. Measures for
      preventing this type of burn injury are also presented.

PMID- 22396674
TI  - Tumescent infiltration of lidocaine and adrenaline for burn surgery.
AB  - Tumescent infiltration is a widely used type of regional anaesthesia for
      cutaneous surgery. This technique makes it possible to administer high doses of
      lidocaine and adrenaline within the safety limits, leading to reduction in pain
      and bleeding during the operation. In this study, tumescent infiltration of
      lidocaine and adrenaline was used in routine procedures of burn surgery such as
      escharectomy, debridement, tangential excision, and skin grafting. In 17 patients
      with scald and flame burns, tumescent infiltration was performed prior to
      surgical procedures under either general anaesthesia or intravenous sedation.
      After 15 minutes, escharectomy, debridement of necrotic tissues, tangential
      excision of the burned skin, removal of the granulation tissue, and harvesting of
      the skin graft were performed. No complications occurred. All vital signs
      remained within safety limits during the operations. Haemorrhage was minimal and
      the operations were thus performed easily and rapidly. During removal of
      granulation tissue, very little blood loss occurred so that both the excision of
      granulation tissue and skin grafting were accomplished rapidly because of the
      minimal need of severe haemostasis. The duration of surgery was considerably
      reduced. No haematoma or bruising developed after surgery. No blood transfusions
      were required as the decline in haematocrit levels was not more than 3%.
      Postoperative analgesia was excellent for the first 8 h, eliminating the need of
      additional measures. Tumescent infiltration of adrenaline and lidocaine is a
      simple, effective and safe technique which facilitates anaesthesia in large areas
      of the burned body surface and leads to less bleeding and easy surgical
      dissection and hydrodissection, allowing fast, easy and painless burn surgery.

PMID- 22396675
TI  - [Post-burn cervical retractions: 45 cases and a survey of the literature].
AB  - Post-burn cervical contractures are the consequence of deep burns, which are
      often neglected or badly managed. They affect the patients' general functioning,
      aesthetic appearance, and psychological state of mind, and treatment can be
      difficult. We conducted a retrospective study that lasted six years (January 2002
      January 2008), analysing epidemiological and clinical features as well as the
      indications and therapeutic results of 49 patients presenting post-burn cervical
      contractures treated at the Moroccan National Burns Centre and in our surgery
      department. Children and young adults were the most affected, with a slight
      female predominance (59.2%). Domestic burns were the most frequent (93.9%) and
      thermal burns were the most prevalent aetiology of the accidents (98.0%). Facial
      burns sequelae were most frequently associated with cervical contractures (67.3%
      of cases), followed by trunk sequelae (46.9%). Moderate and severe cervical
      contractures (Achauer classification) were the most frequent, representing
      respectively 30.6% and 38.8% of the cases. Surgical treatment was based on skin
      graft (67.3% of cases), local plasties (24.5%), and flaps (8.2%). Among the 47
      long-term patients studied, the functional and aesthetic results were considered
      good in 83.0% of cases and medium in 8.5%; repeat surgery was required in the
      remaining cases (8.5%). Epidemiologically (patients' age, sex, burn
      characteristics) and clinically (localization of sequelae, clinical forms), the
      results of our series are consistent with those in the literature. The importance
      of initial management (early excision-graft, pressotherapy, and immobilization by
      neck splint) in reducing the incidence and the severity of cervical burns
      sequelae is demonstrated. When surgical treatment is indicated, the choice of
      repair process essentially depends on the extent of the sequelae. Plasties (Z,
      IC, Y-V...) and local flaps, with or without expansion, are the classic
      indication in minor contractures. In severe and major contractures, opinion is
      divided on the choice between skin grafts and flaps. However, whatever surgical
      treatment is decided upon, rehabilitation is necessary for a final satisfactory
      result.

PMID- 22396677
TI  - MBC News.

PMID- 22396676
TI  - [The Ogilvie syndrome in a severely burned patient].
AB  - The Ogilvie syndrome is an acute colonic dilatation of the previously healthy
      colon, without any organic obstruction. Pathological circumstances such as burns
      and antipsychotic medication have been identified as predisposing elements. The
      incidence of this complication, in the reanimation of burn patients, varies
      between 0.5 to 1%. The purpose of our study is to draw attention to the Ogilvie
      symptom by describing a case with its clinical and paraclinical data, its
      physiopathological causes, and the therapeutic aspects. The clinical picture in
      our patient was characteristic: extensive abdominal meteorism. The abdominal scan
      showed massive colonic dilatation without any mechanical obstacles. The outcome
      was successful after colonoscopic exsufflation. The Ogilvie syndrome is a rare
      occurrence which without effective treatment may result in caecal perforation and
      a poor prognosis. It is therefore necessary to establish the diagnosis early and,
      in particular, to initiate close radiological follow-up after the establishment
      of medical treatment, in which colonoscopy plays an important part.

PMID- 22396678
TI  - The pharmacogenetics of symptom response to antipsychotic drugs.
AB  - Antipsychotic drugs are limited in their efficacy by the relatively poor response
      of negative and cognitive symptoms of schizophrenia as well as by the substantial
      variability in response between patients. Pharmacogenetic studies have sought to
      identify the genetic factors that underlie the individual variability in response
      to treatment, with a past emphasis on dopamine and serotonin receptors as
      candidate genes. Few studies have separated effects on positive and negative
      symptoms, despite the established differences in response to drug treatment
      between these syndromes. Where this has been done most findings are consistent
      with the conclusion that dopamine receptor polymorphisms relate to positive
      symptom response, while negative symptom improvement is influenced by
      polymorphisms of genes involved in 5-HT neurotransmission. A wide range of
      polymorphisms in other candidate genes have been investigated, with some positive
      findings in those genes associated with glutamatergic transmission and/or risk
      factors for schizophrenia. However, there remains a lack of good replicated
      findings; furthermore there is little evidence to support drug-specific genetic
      associations with treatment response. While most past studies focused on single
      candidate genes, technology now permits genome-wide association studies with
      response to antipsychotics. Although not without major limitations, these
      "hypothesis-free" approaches are beginning to identify further important risk
      factors for treatment response. Again there is little consistency between various
      studies, although some of the polymorphisms identified are in genes involved in
      neurodevelopment, which is increasingly being recognized as important in the
      pathophysiology of schizophrenia.

PMID- 22396680
TI  - Use of the terms "schizophrenia" and "schizophrenic" in the South Korean news
      media: a content analysis of newspapers and news programs in the last 10 years.
AB  - OBJECTIVE: In this study, we explored the meaning attributed to the words
      "jungshinbunyeolbyung" (schizophrenia) and "jungshinbunyeol" (schizophrenic) in
      South Korean newspapers and news programs in the last 10 years. METHODS: We
      screened the websites of three national newspapers and the broadcasts of three
      nationwide television news programs from January 1, 2001, to December 31, 2010.
      We classified a total of 490 articles and 257 news segments by category and
      quantitatively and qualitatively analyzed them. The articles and news segments
      were assigned to one of the following categories based on their use of the term
      "schizophrenia": 1) negative, 2) neutral or positive, 3) incidental, and 4)
      metaphorical. RESULTS: The negative viewpoint accounted for 349 incidences
      (46.7%), while the neutral and positive viewpoints included 225 incidences
      (30.1%). Incidental uses accounted for 95 incidences (12.7%), and metaphorical
      uses accounted for 78 incidences (10.4%). The majority of the negative uses
      focused on violence or dangers posed by patients (137 mentions, 37.8%), while the
      metaphorical uses mainly focused on the idea of splitting (51 mentions, or 65%).
      CONCLUSION: This study showed that the South Korean news media do not provide
      balanced information about schizophrenia to the public. This study also showed
      that no significant move has been made toward a more positive use of the term
      since a previous study was conducted on the subject. Although the term
      schizophrenia has given way to "attunement disorder," it will be difficult to
      establish the new term as the standard if the South Korean media continue to use
      the term "schizophrenic symptom." Even though the term has been changed,
      guidelines are necessary to encourage the mass media to provide balanced articles
      and reduce prejudice.

PMID- 22396681
TI  - Psychosocial aspects in girls with idiopathic precocious puberty.
AB  - OBJECTIVE: Precocious puberty leads to discrepancies between physical and
      chronological age. The aim of the present study was to evaluate behavioral
      patterns and social competences in 34 girls with idiopathic precocious puberty.
      METHODS: Height, body weight, and BMI were determined, and pubertal development
      was assessed. The Korean-child behavior checklist (K-CBCL) was completed by
      parents. RESULTS: 1) Body weight and BMI were significantly higher in precocious
      puberty group than in the control group. 2) T scores of total social competence
      and school scales of K-CBCL were significantly higher in the precocious puberty
      group than in the control group. 3) T scores of externalizing problems and total
      behavior problems of K-CBCL were also significantly higher in the precocious
      puberty group. 4) T scores of thought problems and attention problems of K-CBCL
      were significantly higher in the precocious puberty group than the control group.
      CONCLUSION: Although girls with precocious puberty had more behavioral problems,
      no significant differences were observed between the two study groups in terms of
      clinically-important T scores. However, the concerns of parents and patients
      regarding behavioral and emotional changes might be most important when
      evaluating psychosocial problems. Early recognition, sufficient understanding,
      communication with patients and parents regarding physical developmental
      difference from children in the same age, can improve the self-image of those
      with precocious puberty.

PMID- 22396679
TI  - Alcohol and cognition in the elderly: a review.
AB  - Consumption of large amounts of alcohol is known to have negative effects, but
      consumption in smaller amounts may be protective. The effect of alcohol may be
      greater in the elderly than in younger adults, particularly with regard to
      cognition. However, the drinking pattern that will provide optimal protection
      against dementia and cognitive decline in the elderly has not been systematically
      investigated. The present paper is a critical review of research on the effect of
      alcohol on cognitive function and dementia in the elderly. Studies published from
      1971 to 2011 related to alcohol and cognition in the elderly were reviewed using
      a PubMed search. Alcohol may have both a neurotoxic and neuroprotective effect.
      Longitudinal and brain imaging studies in the elderly show that excessive alcohol
      consumption may increase the risk of cognitive dysfunction and dementia, but low
      to moderate alcohol intake may protect against cognitive decline and dementia and
      provide cardiovascular benefits. Evidence suggesting that low to moderate alcohol
      consumption in the elderly protects against cognitive decline and dementia
      exists; however, because of varying methodology and a lack of standardized
      definitions, these findings should be interpreted with caution. It is important
      to conduct more, well-designed studies to identify the alcohol drinking pattern
      that will optimally protect the elderly against cognitive decline and dementia.

PMID- 22396682
TI  - The relationship between religion and mental disorders in a Korean population.
AB  - OBJECTIVE: The question of whether religion has beneficial or detrimental effects
      on the mental well-being of the adult individual is debatable. Because most
      Korean citizens are free to select their own religion, there is a higher
      proportion of non-believers than believers among the Korean population. The aim
      of this research was to investigate the association between spiritual values and
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition mental
      disorders in Korea across all types of belief systems, including Koreans not
      affiliated with a particular religion. METHODS: The Korean version of the
      Composite International Diagnostic Interview 2.1 was used to interview 6,275
      people across South Korea in 2001. While controlling for age and sex, we used
      logistic regression to analyze the relationship between mental disorders (both
      current and past) and the types of religion and spiritual values. RESULTS: Strong
      spiritual values were positively associated with increased rates of current
      depressive disorder and decreased rates of current alcohol use disorder. Using
      "atheist" as the reference category, Catholics had higher lifetime odds of single
      episodes of depression whilst Protestants had higher lifetime odds of anxiety
      disorder and lower lifetime odds of alcohol use disorders. CONCLUSION: The
      results of this study suggest that depressive episodes often lead to a search for
      spirituality and that religion may be helpful in overcoming depression or
      becoming less vulnerable to relapsing. The associations between religion,
      spiritual values, and mental health have not been fully elucidated and warrant
      further exploration.

PMID- 22396683
TI  - Development and validation of a screening scale for depression in Korea: the Lee
      and Rhee Depression Scale.
AB  - OBJECTIVE: The aim of this study was to develop a culturally sensitive instrument
      that addressed how individuals express and experience depression to detect this
      disorder in Koreans. We also assessed the validity, reliability, and diagnostic
      utility of this scale (Lee and Rhee Depression Scale; LRDS). METHODS: The sample
      consisted of 3,697 normal adults selected from 12 administrative districts (Do)
      and 448 Korean patients diagnosed with depression using the Structured Clinical
      Interview for DSM-IV Axis I disorders (SCID-I). Reliability was calculated using
      Cronbach's alpha. Construct validity, discriminant validity, and concurrent
      validity were also measured. Receiver-operator-characteristic (ROC) analysis was
      employed to evaluate diagnostic efficiency. RESULTS: The LRDS was found to be a
      reliable instrument (Cronbach's alpha=0.95) consisting of six factors: negative
      thinking about the future, negative thinking about the self, worry and agitation,
      depressed mood, somatization, and loss of volition. Comparison of LRDS scores
      discriminated the group of patients with depression from the normal individuals
      in the control group. The measure showed good concurrent validity in that scores
      were significantly and strongly correlated with scores on established scales such
      as the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HAM
      D), and the D scale of the Minnesota Multiphasic Personality Inventory-second
      edition (MMPI-2). Diagnostic efficiency was 77.7%, and the cut-off scores were 65
      for males and 70 for females. CONCLUSION: To our knowledge, this is the first
      study to develop a depression-screening scale on the basis of Korean patients'
      complaints about the disorder. As a culturally sensitive tool, the LRDS will be
      useful in clinical and research settings in Korea.

PMID- 22396684
TI  - Korean Anxiety Sensitivity Index-3: its factor structure, reliability, and
      validity in non-clinical samples.
AB  - OBJECTIVE: The aim here is to examine the factorial structure, internal
      consistency, and concurrent validity of the Korean version of the Anxiety
      Sensitivity Index-3 (K-ASI-3) in student samples in Korea. Also, we investigated
      the cross-cultural differences in the Social Concerns factor. METHODS: K-ASI-3
      was administered to non clinical samples in Korea. Internal consistency,
      exploratory factor analysis (EFA), and confirmatory factor analysis (CFA) were
      undertaken to examine the factorial structure and reliability of the K-ASI-3.
      RESULTS: Results from CFA comparing our data to factor solutions commonly
      reported as representative of European-American samples indicated an adequate
      fit. The K-ASI-3 showed good performance on the indices of internal consistency
      and concurrent validity. In addition, using regression analyses, we found the
      Social Concerns factor is most strongly related to life satisfaction and worry.
      However, we found no evidence that Korean college students express more Social
      Concerns than their European Caucasian counterparts. CONCLUSION: The authors
      demonstrate that the K-ASI-3 has highly internally consistent and
      psychometrically sound items, and that it reliably measures three lower-order
      domains assessing Physical, Social, and Cognitive Concerns.

PMID- 22396685
TI  - A comparison of reliability and construct validity between the original and
      revised versions of the Rosenberg Self-Esteem Scale.
AB  - OBJECTIVE: The Rosenberg Self-Esteem Scale (RSES) is a widely used instrument
      that has been tested for reliability and validity in many settings; however, some
      negative-worded items appear to have caused it to reveal low reliability in a
      number of studies. In this study, we revised one negative item that had
      previously (from the previous studies) produced the worst outcome in terms of the
      structure of the scale, then re-analyzed the new version for its reliability and
      construct validity, comparing it to the original version with respect to fit
      indices. METHODS: In total, 851 students from Chiang Mai University (mean age:
      19.51+/-1.7, 57% of whom were female), participated in this study. Of these, 664
      students completed the Thai version of the original RSES - containing five
      positively worded and five negatively worded items, while 187 students used the
      revised version containing six positively worded and four negatively worded
      items. Confirmatory factor analysis was applied, using a uni-dimensional model
      with method effects and a correlated uniqueness approach. RESULTS: The revised
      version showed the same level of reliability (good) as the original, but yielded
      a better model fit. The revised RSES demonstrated excellent fit statistics, with
      chi2=29.19 (df=19, n=187, p=0.063), GFI=0.970, TFI=0.969, NFI=0.964, CFI=0.987,
      SRMR=0.040 and RMSEA=0.054. CONCLUSION: The revised version of the Thai RSES
      demonstrated an equivalent level of reliability but a better construct validity
      when compared to the original.

PMID- 22396686
TI  - Impaired design fluency is a marker of pathological cognitive aging; results from
      the Korean longitudinal study on health and aging.
AB  - OBJECTIVE: We investigated neuropsychological markers that can be used to
      discriminate pathological cognitive aging from normal cognitive aging. METHODS:
      We administered frontal lobe function tests including the Wisconsin Card Sorting
      Test (WCST), digit span test, lexical fluency test, fixed condition design
      fluency test, and Trail Making Test B (TMT-B) to 92 individuals with pathological
      cognitive aging (PCA) and 222 individuals with normal cognitive aging (NCA). We
      examined the main effects of participants' diagnoses (PCA, NCA) and age (65-69
      years old, 70-74 years old and 75 years old or over) on their test performance
      using multivariate analysis of variance. RESULTS: The main effects of both the
      diagnosis (F=2.860, p=0.002) and the age group (F=2.484, p<0.001) were
      significant. The PCA group showed lower performance on the backward digit span
      test (F=14.306, p<0.001), fixed condition design fluency test (F=8.347, p=0.004)
      and also exhibited perseverative errors in the WCST (F=4.19, p=0.042) compared
      with the NCA group. The main effect of the diagnosis on the backward digit span
      test and the fixed condition design fluency test remained significant after
      Bonferroni correction. The main effect of age remained significant in the TMT-B
      (F=8.737, p<0.001) after Bonferroni correction. Other test scores were not
      influenced by diagnosis or age. CONCLUSION: The design fluency task may be a good
      neuropsychological marker to assess pathological cognitive aging.

PMID- 22396687
TI  - The effect of aging and severity of sleep apnea on heart rate variability indices
      in obstructive sleep apnea syndrome.
AB  - OBJECTIVE: This study aims to analyze how much heart rate variability (HRV)
      indices discriminatively respond to age and severity of sleep apnea in the
      obstructive sleep apnea syndrome (OSAS). METHODS: 176 male OSAS patients were
      classified into four groups according to their age and apnea-hypopnea index
      (AHI). The HRV indices were compared via analysis of covariance (ANCOVA). In
      particular, the partial correlation method was performed to identify the most
      statistically significant HRV indices in the time and frequency domains. Stepwise
      multiple linear regressions were further executed to examine the effects of age,
      AHI, body mass index (BMI), systolic blood pressure (SBP), diastolic blood
      pressure (DBP), and sleep parameters on the significant HRV indices. RESULTS: The
      partial correlation analysis yielded the NN50 count (defined as the number of
      adjacent R-wave to R-wave intervals differing by more than 50 ms) and low
      frequency/high frequency (LF/HF) ratio to be two most statistically significant
      HRV indices in both time and frequency domains. The two indices showed
      significant differences between the groups. The NN50 count was affected by age
      (p<0.001) and DBP (p=0.039), while the LF/HF ratio was affected by AHI (p<0.001),
      the amount of Stage 2 sleep (p=0.005), and age (p=0.021) in the order named in
      the regression analysis. CONCLUSION: The NN50 count more sensitively responded to
      age than to AHI, suggesting that the index is mainly associated with an age
      related parasympathetic system. On the contrary, the LF/HF ratio responded to AHI
      more sensitively than to age, suggesting that it is mainly associated with a
      sympathetic tone likely reflecting the severity of sleep apnea.

PMID- 22396688
TI  - Comparison of treatment adherence between selective serotonin reuptake inhibitors
      and moclobemide in patients with social anxiety disorder.
AB  - OBJECTIVE: With respect to the pharmacotherapy of social anxiety disorder (SAD),
      it has been suggested that treatment duration is an important factor that can
      significantly predict responses. The present study aimed to compare the treatment
      adherence of SAD patients who were taking either SSRIs or reversible inhibitors
      of MAO-A (moclobemide) by measuring treatment duration and all-cause
      discontinuation rates of pharmacotherapy in a natural clinical setting. METHODS:
      We retrospectively analysed the data of 172 patients diagnosed with SAD.
      Depending on their medication, we divided the patients into two groups, SSRI
      (n=54) or moclobemide (n=118). The expected number of all-cause discontinuation
      every 2 weeks after starting treatment was calculated by life table survival
      methods. A multi-variable Cox proportional hazard regression was used to analyze
      the potential influence of explanatory variables. RESULTS: Treatment duration was
      significantly longer in the SSRI group [46.41+/-56.96, median=12.0 (weeks)] than
      in the moclobemide group [25.53+/-34.74, median=12.0 (weeks), Z=2.352, p=0.019].
      Overall, all-cause discontinuation rates were significantly lower with SSRIs
      (81%) than moclobemide (96%, chi2=4.532, p=0.033). CONCLUSION: The SSRI group had
      a longer treatment duration and lower all-cause discontinuation rate than
      moclobemide. Further, only the type of medication had a significant effect on all
      cause discontinuation rates and therefore, we could predict better treatment
      adherence with the SSRIs in the treatment of SAD.

PMID- 22396689
TI  - Usefulness of LDAEP to predict tolerability to SSRIs in major depressive
      disorder: a case report.
AB  - We report here a patient with major depressive disorder who experienced severe
      adverse effects after the administration of SSRIs (serotonin selective reuptake
      inhibitors) without improvement of his depressive symptoms. These adverse effects
      disappeared and his depressive symptoms improved after discontinuation of the
      SSRIs and the administration of tianeptine. The patient exhibited a low value for
      the loudness dependent of auditory evoked potentials (LDAEP) -0.14 at baseline,
      which means that his central serotonergic neurotransmission was already highly
      active. We assumed that it was this high serotonergic activity that rendered him
      unresponsive to SSRIs, and brought on him the adverse effects, and that the
      tianeptine was effective due to the lack of serotonin reuptake inhibitory action.
      Thus, we suggest that LDAEP can be used to predict an individual patient's
      tolerability and clinical response to SSRIs in major depression.

PMID- 22396690
TI  - Rapid-onset hyponatremia induced by duloxetine in a middle-aged male with
      depression and somatic symptoms.
AB  - Duloxetine is a relatively balanced selective serotonin and noradrenaline
      reuptake inhibitor. We report a case of hyponatremia induced by duloxetine
      developed rapidly after starting the medication in a middle-aged male with
      multiple somatic symptoms and depression. Two days after discontinuation of
      duloxetine and management with hypertonic saline as well as fluid restriction,
      the serum sodium level normalized. The patient had two risk factors for
      developing hyponatremia, such as severe body weight loss and pneumonia.
      Therefore, when treating patients with depression and somatic symptoms,
      especially with risk factors for developing hyponatremia, close monitoring for
      clinical and laboratory evidence of hyponatremia may be essential.

PMID- 22396691
TI  - Comment on "Serial monitoring of lead aVR in patients with prolonged
      unconsciousness following tricyclic antidepressant overdose".

PMID- 22396693
TI  - Knowledge gap regarding low density lipoprotein-cholesterol levels in koreans.

PMID- 22396692
TI  - A long road for stem cells to cure sick hearts: update on recent clinical trials.
AB  - The contribution of stem cells to cure damaged hearts has finally been unraveled.
      A large number of preclinical and clinical studies have showed beneficial
      outcomes after myocardial infarction. In this review, the current understanding
      of stem cell therapy in preclinical and clinical experiences is summarized. Stem
      cells from bone marrow have shown a potential to improve cardiac performance
      after myocardial infarction in animal and early clinical studies. Clinical trials
      from all over the world have provided safety assessments of stem cell therapy
      with marginal improvement of clinical outcomes. Thus, further investigations
      should be encouraged to resolve the discrepancies between studies, clinical
      issues, and unclear translational findings. This review provides information and
      commentary on key trials for stem cell-based treat-ment of cardiovascular
      disease.

PMID- 22396694
TI  - The concurrent chronic total occlusion in a non-infarct artery strongly associate
      with poor long-term prognosis in patients with acute myocardial infarction and
      multivessel coronary disease.

PMID- 22396695
TI  - The prevalence, awareness and treatment of high low density lipoprotein
      cholesterol in korean adults without coronary heart diseases - the third Korea
      national health and nutrition examination survey, 2005 -.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to estimate the
      prevalence, awareness and treatment of high low density lipoprotein-cholesterol
      (LDL-C) level in Korean adults without coronary heart disease. SUBJECTS AND
      METHODS: National representative cross-sectional surveys, data of 5248 Korean
      adults (2246 men and 3002 women) aged between 20 and 79 years from the Third
      Korea National Health and Nutrition Examination Survey (KNHANES III, 2005) was
      used. High LDL-C level was defined with the risk prediction algorithm published
      by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP
      III). RESULTS: The prevalence of the Korean adults with high LDL-C level who need
      therapeutic lifestyle changes was 19.9%, treatment with lipid-lowing medication
      was 2.1% and awareness of this condition was 7.9%. Meanwhile, the prevalence of
      the Korean with very high LDL-C level who should be considered for drug therapy
      was 13.5%, treatment with lipid-lowing medication was 2.7% and awareness of this
      condition was 8.1%. Overall, 47.9% (60.3% in male and 39.1% in female) of
      participants had a single lipid disorder (high LDL-C, high triglycerides: >=200
      mg/dL, low high density lipoprotein-cholesterol: <40 mg/dL), whereas 15.5% (23.5%
      in male and 9.7% in female) had at least two. Only 1.9% (2.8% in male and 1.2% in
      female) of all participants had all three lipid abnormalities as defined.
      CONCLUSION: These findings indicate that continuous efforts are needed to
      increase awareness and treatment of high LDL-C level in our population to prevent
      cardiovascular disease.

PMID- 22396696
TI  - Impact of multivessel coronary disease with chronic total occlusion on one-year
      mortality in patients with acute myocardial infarction.
AB  - BACKGROUND AND OBJECTIVES: The impact of multivessel coronary disease (MVD) with
      chronic total occlusion (CTO) on one-year mortality in patients with acute
      myocardial infarction (AMI) is not clearly known. We investigated the impact of
      MVD with concurrent CTO lesion on one-year mortality in patients with AMI.
      SUBJECTS AND METHODS: We studied 1008 consecutive patients who underwent coronary
      angiography between November 2005 and December 2008 with a diagnosis of AMI.
      RESULTS: Among 1008 patients, 432 patients (43%) had MVD, and 88 patients (8.7%)
      had CTO lesion. The one-year overall mortality was higher in patients with MVD
      than in patients with single vessel disease (SVD) (10.2% vs. 5.9%, p=0.012).
      However, the one-year overall mortality was not significantly higher in patients
      with CTO lesion than in patients without that lesion (12.5% vs. 7.3%, p=0.080).
      In multivariate analysis, independent predictors of one-year overall mortality
      were age older than 65 years {hazard ratio (HR) 2.41, 95% confidence interval
      (CI): 1.43 to 4.08}, Killip class >=III (HR 3.59, 95% CI: 2.24 to 5.77), ST
      elevation myocardial infarction (HR 2.45, 95% CI: 1.49 to 4.05) and MVD (HR 1.76,
      95% CI: 1.07 to 2.89). CONCLUSION: Patients with MVD showed higher one-year
      mortality than patients with SVD. However, the presence of CTO was not an
      independent predictor of one-year mortality in this study that included patients
      with successfully revascularized CTO lesion.

PMID- 22396697
TI  - Higher plasma thrombospondin-1 levels in patients with coronary artery disease
      and diabetes mellitus.
AB  - BACKGROUND AND OBJECTIVES: Thrombospondin-1 (TSP-1) is associated with
      atherosclerosis in animals with diabetes mellitus (DM). But, no study has
      investigated the role of TSP-1 in human atherosclerosis. This study investigated
      the relationship among plasma TSP-1 concentration, DM, and coronary artery
      disease (CAD). SUBJECTS AND METHODS: The study involved 374 consecutive subjects
      with suspected CAD, who had undergone coronary angiography to evaluate effort
      angina. Patients were divided into four groups as follows: DM(-) and CAD(-), DM(
      ) and CAD(+), DM(+) and CAD(-), and DM (+) and CAD(+). RESULTS: We found that
      plasma TSP-1 levels were higher in patients with DM(+) and CAD(+) (n=103) than
      those in other patients (n=271) (p<0.01). A multivariate analysis showed that
      male gender {odds ratio (OR), 2.728; 95% confidence interval (CI), 1.035-7.187},
      high density lipoprotein-cholesterol (OR, 0.925; 95% CI, 0.874-0.980), glycated
      hemoglobin (OR, 1.373; 95% CI, 1.037-1.817), and plasma TSP-1 (OR, 1.004; 95% CI,
      1.000-1.008) levels were independently associated with the presence of CAD in
      patients with DM. CONCLUSION: Plasma TSP-1 levels were higher in patients with
      DM(+) and CAD(+) than those in other patients, and plasma TSP-1 levels were
      independently associated with the presence of CAD in patients with DM. These
      findings show a possible link between human plasma TSP-1 concentration and CAD in
      patients with DM.

PMID- 22396698
TI  - Comparison of the radial artery and saphenous vein as composite grafts in off
      pump coronary artery bypass grafting in elderly patients: a randomized controlled
      trial.
AB  - BACKGROUND AND OBJECTIVES: Arterial grafts have a better long-term patency rate
      than saphenous vein (SV) when used in off-pump coronary artery bypass surgery
      (OPCAB). However, arterial grafts in elderly patients are often diseased. We
      sought to compare the early outcomes achieved by using the two different types of
      composite grafts. SUBJECTS AND METHODS: We conducted a randomized trial to
      compare radial artery (RA) and SV composite grafts based on the in situ left
      internal mammary artery in 60 elderly (>70 years old) patients, who were
      scheduled to undergo OPCAB. Clinical outcomes and 1-year postoperative CT
      angiography results were compared. The quality of the conduit was evaluated by
      employing vascular ultrasonography, optical coherence tomography (OCT), and
      histologic examination. RESULTS: No differences in immediate postoperative
      morbidity and mortality were observed between the two groups. Early postoperative
      CT angiography revealed a SV patency rate of 100%, which was not different from
      that of RA composite grafts (99.1%). CT angiography after a year showed an
      overall patency rate of 96.3%. The overall patency rate of the SV group at 1 year
      was 94.7%, which was similar to that of the RA group (97.4%). Also, there was no
      difference in overall survival rate between the two groups. Vascular
      ultrasonographic images showed strong correlations between OCT and
      histopathology. CONCLUSION: Our analysis of early outcomes revealed that the SV
      could be used as an alternative composite graft to the RA in elderly patients.
      Vascular ultrasonography is an accurate, real-time, and reproducible method for
      assessing the quality of the RA conduit.

PMID- 22396699
TI  - Trends in Oral Anticoagulation Therapy Among Korean Patients With Atrial
      Fibrillation: The KORean Atrial Fibrillation Investigation.
AB  - BACKGROUND AND OBJECTIVES: Anticoagulation with vitamin K antagonists (VKAs) such
      as warfarin provides effective stroke prophylaxis in patients with atrial
      fibrillation (AF). We conducted a large multicenter survey of Korean patients
      with AF to determine trends in VKA use. SUBJECTS AND METHODS: Eligible patients
      were adults with AF that had been prescribed VKAs. Medical records from a total
      of 5616 patients {mean age 63.6+/-12.2 years, male 3150 (56.1%)} in 27 hospitals
      from Jan. 2001 to Oct. 2007 were reviewed. RESULTS: The mean international
      normalized ratio (INR) was 2.04+/-0.64, and mean dosage of VKA was 3.66+/-1.50
      mg. Individuals in their sixties (1852 patients) accounted for about one third of
      patients studied. As patients grew older, INR increased and VKA dosage decreased.
      The dosage of VKA in male patients was larger than that in females for all ages.
      A total of 2146 (42.4%) patients had an INR of 2-3, and less than 40% patients in
      their sixties had an INR within optimal range. The dosage of oral anticoagulant
      for optimal INR level was 3.71 mg. CONCLUSION: In this study, less than half of
      the Korean patients with AF on VKA reached the therapeutic range of INR. Mean
      dosage of VKA was 3.66+/-1.50 mg, and the dosage of oral anticoagulant for
      optimal INR level was 3.71 mg, which decreased with age.

PMID- 22396700
TI  - Recurrent very late stent thrombosis in a systemic lupus erythematous patient.
AB  - Coronary artery disease is the most important cause of mortality in patients with
      systemic lupus erythematous (SLE). After stenting for coronary artery disease in
      SLE patients similar to non-SLE patients, the risk of stent thrombosis is always
      present. Although there are reports of stent thrombosis in SLE patients, very
      late recurrent stent thrombosis is rare. We experienced a case of very late
      recurrent stent thrombosis (4 times) in a patient with SLE.

PMID- 22396701
TI  - Percutaneous retrieval of an embolized central venous chemoport in a patient with
      colon cancer.
AB  - The central access device is commonly used as a route of chemotherapuetic agents
      in patients with malignant diseases for its convenient and safety for insertion.
      This report describes a case of 66-year-old man with colon cancer who suffered a
      rare complication in which a chemoport embolized into the inferior vena cava and
      it was successfully retrieved by a percutaneous approach using a goose neck
      snare.

PMID- 22396702
TI  - Below the knee intervention using multidisciplinary methods including an
      antegrade, retrograde approach without the use of a sheath but with a plaque
      excision device.
AB  - Below the knee (BTK) interventions are increasing in patients with rest pain or
      critical limb ischemia, and these interventions are frequently successful in
      facilitating limb salvage. New intervention techniques and devices allow
      successful recanalization of occluded BTK arteries. Here, we report a case of
      successful recanalization of BTK arteries using multidisciplinary methods,
      including an antegrade approach and retrograde approach without the use of a
      sheath, but with simple balloon angioplasty, and plaque excision using Silverhawk
      atherectomy device.

PMID- 22396703
TI  - Catecholaminergic polymorphic ventricular tachycardia in a patient with recurrent
      exertional syncope.
AB  - A 16-year-old male with a prior history of recurrent syncope was referred to our
      hospital after being resuscitated from cardiac arrest developed while playing
      volleyball. His electrocardiogram (ECG) demonstrated ventricular fibrillation at
      a local emergency department. After referral, an ECG showed bidirectional
      ventricular tachycardia (VT) and nonsustained Torsade de Pointes. Two days later,
      his heart rate became regular, and no additional episodes of VT were observed.
      His ECG showed sinus rhythm with a corrected QT interval of 423 msec, and two
      dimensional echocardiography was unremarkable. We made the diagnosis of a
      catecholaminergic polymorphic VT. However, only premature ventricular complex
      bigeminy was induced on exercise ECG and epinephrine infusion tests, and the
      patient showed no episodes of syncope. His father and mother had different
      missense mutations in the cardiac ryanodine receptor on genetic testing. The
      proband had both mutations in different alleles and was symptomatic. It was
      recommended that the patient avoid competitive physical activities, and a beta
      blocker was prescribed.

PMID- 22396704
TI  - A Case of Acute Carbon Monoxide Poisoning Resulting in an ST Elevation Myocardial
      Infarction.
AB  - Carbon monoxide (CO) is a well-known chemical asphyxiant, which causes tissue
      hypoxia with prominent neurological and cardiovascular injury. After exposure to
      CO, several cardiac manifestations have been reported, including arrhythmias,
      acute myocardial infarction, and pulmonary edema. However, an ST elevation
      myocardial infarction (STEMI) due to CO poisoning is a very rare presentation,
      and the treatment for STEMI due to CO poisoning is not well established. Here, we
      report a rare case of STEMI complicated by increased thrombogenicity secondary to
      acute CO poisoning and complete revascularization after antithrombotic treatment.

PMID- 22396705
TI  - A case of severe aortic valve regurgitation caused by an ascending aortic
      aneurysm in a young patient with autosomal dominant polycystic kidney disease and
      normal renal function.
AB  - Aortic aneurysm is one several well-known cardiovascular complications in
      patients with autosomal dominant polycystic kidney disease (ADPCKD). Commonly
      affected site of aortic aneurysm and its related dissection in ADPCKD is
      abdominal aorta. Long standing hypertension, haemodialysis, old age are closely
      related with discovering of aortic aneurysm and dissection in ADPCKD. However,
      thoracic aortic aneurysms and its related severe aortic regurgitations (ARs) are
      rare in younger patients suffering from ADPCKD, especially ones who have normal
      renal function. Here, we report a case involving a 27-year-old Asian male patient
      with severe AR due to an ascending aneurysm of the thoracic aorta associated with
      ADPCKD. The patient had normal renal function without Marfan's habitus. The AR
      and thoracic aortic aneurysm were corrected surgically.

PMID- 22396706
TI  - Endovascular Stent Grafting via the Left Radial Artery for a Spontaneous Isolated
      Dissecting Rupture of the Superior Mesenteric Artery.

PMID- 22396707
TI  - Chronic critical limb ischemia.
AB  - BACKGROUND: Some 40 000 lower limb amputations are performed in Germany each
      year, 70% of them in diabetics. About 80% of all major amputations may be
      preventable with the use of new interventional and vascular surgical procedures,
      particularly on the arteries of the leg and foot. We present the current state of
      the art in revascularization techniques and evaluate their usefulness for
      preservation of the lower limb. METHODS: This overview is based on the guidelines
      for the diagnosis and treatment of peripheral artery disease (PAD) and diabetic
      foot syndrome (DFS) that have been issued by the American Heart Association
      (AHA), the American College of Cardiology (ACC), the German Society of Angiology
      (DGA), the Trans-Atlantic Intersociety Consensus (TASC II), the German Society of
      Vascular Surgery (DGG), and the German Diabetes Society (DDG). A selective search
      in PubMed for relevant articles that appeared from 2000 to 2011 was conducted
      with the search terms "pedal bypass," "vascular intervention crural pedal," and
      "crural-pedal revascularization." RESULTS: Most of the data on crural and pedal
      revascularization are derived from small-scale studies. The few comparative
      studies of interventional treatments and bypass surgery have not revealed any
      significant differences in outcome, but all studies of revascularization have
      shown good success rates for lower limb preservation. CONCLUSION: Though the data
      are still sparse, the high reported rates of limb preservation imply that
      peripheral revascularization techniques can play a major role in the treatment of
      chronic critical limb ischemia (CLI). Therefore, these techniques are recommended
      without exception by the current guidelines.

PMID- 22396708
TI  - The treatment of patients with severe and multiple traumatic injuries.
AB  - BACKGROUND: The care of severely and multiply injured patients is an
      interdisciplinary challenge. The only existing German-language guideline up to
      now has been the S1-guideline issued in 2002 by the German Society for Trauma
      Surgery (Deutsche Gesellschaft fur Unfallchirurgie, DGU). In this article, we
      present a new, comprehensive, evidence and consensus based S3-guideline for the
      treatment of severely and multiply injured patients in the pre-hospital and early
      in-hospital phases which has been developed with the aim of structural and
      procedural quality optimization. Its implementation should lower these patients'
      mortality and improve their quality of life. METHODS: The guideline was developed
      by a panel consisting of 18 delegates from 11 specialty societies under the lead
      of the DGU, with designated coordinators for each of three phases of treatment:
      the pre-hospital phase, the emergency-room phase, and the emergency surgery
      phase. The key questions to be answered were determined by vote, and then the
      relevant literature (in English and German, 1995-2010) was systematically
      searched and evaluated. Key recommendations with explanatory texts were
      formulated and agreed upon in a nominal group process (NGP) with five consensus
      conferences and three further Delphi rounds. RESULTS: 264 recommendations were
      issued: 66 for the pre-hospital phase, 102 for the emergency-room phase, and 96
      for the emergency surgery phase. The three phases were subcategorized according
      to organizational and anatomical considerations. Topics of major emphasis were,
      in the pre-hospital phase, the establishment and implementation of correct
      priorities for treatment; in the emergency-room phase, the creation of clear
      structures and processes; and, in the emergency surgery phase, the avoidance of
      secondary injury (i.e., the principle of damage control). CONCLUSION: This
      guideline can only improve outcomes if it is implemented in routine practice.
      Aside from the guideline itself, the DGU trauma network (www.dgu
      traumanetzwerk.de) has issued a set of directions as an aid to its
      implementation.

PMID- 22396709
TI  - Many causes are unknown.

PMID- 22396710
TI  - Possible magnesium deficiency should be investigated.

PMID- 22396711
TI  - Fecal biomarkers.

PMID- 22396712
TI  - Sexual abuse.

PMID- 22396713
TI  - Examine the eyes.

PMID- 22396715
TI  - Poor evidence based medicine.

PMID- 22396716
TI  - Objective is questionable.

PMID- 22396717
TI  - Niche use at best.

PMID- 22396719
TI  - Increased risk of bilateral infection.

PMID- 22396721
TI  - Wafer-scale fabrication of high-aspect ratio nanochannels based on edge
      lithography technique.
AB  - This paper introduced a wafer-scale fabrication approach for the preparation of
      nanochannels with high-aspect ratio (the ratio of the channel depth to its
      width). Edge lithography was used to pattern nanogaps in an aluminum film, which
      was functioned as deep reactive ion etching mask thereafter to form the
      nanochannel. Nanochannels with aspect ratio up to 172 and width down to 44 nm
      were successfully fabricated on a 4-inch Si wafer with width nonuniformity less
      than 13.6%. A microfluidic chip integrated with nanometer-sized filters was
      successfully fabricated by utilizing the present method for geometric
      controllable nanoparticle packing.

PMID- 22396722
TI  - A new fabrication technique to form complex polymethylmethacrylate microchannel
      for bioseparation.
AB  - Recent studies show that reduction in cross-sectional area can be used to improve
      the concentration factor in microscale bioseparations. Due to simplicity in
      fabrication process, a step reduction in cross-sectional area is generally
      implemented in microchip to increase the concentration factor. But the sudden
      change in cross-sectional area can introduce significant band dispersion and
      distortion. This paper reports a new fabrication technique to form a gradual
      reduction in cross-sectional area in polymethylmethacrylate (PMMA) microchannel
      for both anionic and cationic isotachophoresis (ITP). The fabrication technique
      is based on hot embossing and surface modification assisted bonding method. Both
      one-dimensional and two-dimensional gradual reduction in cross-sectional area
      microchannels were formed on PMMA with high fidelity using proposed techniques.
      ITP experiments were conducted to separate and preconcentrate fluorescent
      proteins in these microchips. Thousand fold and ten thousand fold increase in
      concentrations were obtained when 10 * and 100 * gradual reduction in cross
      sectional area microchannels were used for ITP.

PMID- 22396723
TI  - 3D Morphology, ultrastructure and development of Ceratomyxa puntazzi stages:
      first insights into the mechanisms of motility and budding in the Myxozoa.
AB  - Free, amoeboid movement of organisms within media as well as substrate-dependent
      cellular crawling processes of cells and organisms require an actin cytoskeleton.
      This system is also involved in the cytokinetic processes of all eukaryotic
      cells. Myxozoan parasites are known for the disease they cause in economical
      important fishes. Usually, their pathology is related to rapid proliferation in
      the host. However, the sequences of their development are still poorly
      understood, especially with regard to pre-sporogonic proliferation mechanisms.
      The present work employs light microscopy (LM), electron microscopy (SEM, TEM)
      and confocal laser scanning microscopy (CLSM) in combination with specific stains
      (Nile Red, DAPI, Phalloidin), to study the three-dimensional morphology,
      motility, ultrastructure and cellular composition of Ceratomyxa puntazzi, a
      myxozoan inhabiting the bile of the sharpsnout seabream.Our results demonstrate
      the occurrence of two C. puntazzi developmental cycles in the bile, i.e. pre
      sporogonic proliferation including frequent budding as well as sporogony,
      resulting in the formation of durable spore stages and we provide unique details
      on the ultrastructure and the developmental sequence of bile inhabiting
      myxozoans. The present study describes, for the first time, the cellular
      components and mechanisms involved in the motility of myxozoan proliferative
      stages, and reveals how the same elements are implicated in the processes of
      budding and cytokinesis in the Myxozoa. We demonstrate that F-actin rich
      cytoskeletal elements polarize at one end of the parasites and in the filopodia
      which are rapidly de novo created and re-absorbed, thus facilitating
      unidirectional parasite motility in the bile. We furthermore discover the
      myxozoan mechanism of budding as an active, polarization process of cytokinesis,
      which is independent from a contractile ring and thus differs from the mechanism,
      generally observed in eurkaryotic cells. We hereby demonstrate that CLSM is a
      powerful tool for myxozoan research with a great potential for exploitation, and
      we strongly recommend its future use in combination with in vivo stains.

PMID- 22396724
TI  - The PIKfyve inhibitor YM201636 blocks the continuous recycling of the tight
      junction proteins claudin-1 and claudin-2 in MDCK cells.
AB  - Tight junctions mediate the intercellular diffusion barrier found in epithelial
      tissues but they are not static complexes; instead there is rapid movement of
      individual proteins within the junctions. In addition some tight junction
      proteins are continuously being endocytosed and recycled back to the plasma
      membrane. Understanding the dynamic behaviour of tight junctions is important as
      they are altered in a range of pathological conditions including cancer and
      inflammatory bowel disease. In this study we investigate the effect of treating
      epithelial cells with a small molecule inhibitor (YM201636) of the lipid kinase
      PIKfyve, a protein which is involved in endocytic trafficking. We show that MDCK
      cells treated with YM201636 accumulate the tight junction protein claudin-1
      intracellularly. In contrast YM201636 did not alter the localization of other
      junction proteins including ZO-1, occludin and E-cadherin. A biochemical
      trafficking assay was used to show that YM201636 inhibited the endocytic
      recycling of claudin-1, providing an explanation for the intracellular
      accumulation. Claudin-2 was also found to constantly recycle in confluent MDCK
      cells and treatment with YM201636 blocked this recycling and caused accumulation
      of intracellular claudin-2. However, claudin-4 showed negligible endocytosis and
      no detectable intracellular accumulation occurred following treatment with
      YM201636, suggesting that not all claudins show the same rate of endocytic
      trafficking. Finally, we show that, consistent with the defects in claudin
      trafficking, incubation with YM201636 delayed formation of the epithelial
      permeability barrier. Therefore, YM201636 treatment blocks the continuous
      recycling of claudin-1/claudin-2 and delays epithelial barrier formation.

PMID- 22396726
TI  - A climate change vulnerability assessment of California's at-risk birds.
AB  - Conservationists must develop new strategies and adapt existing tools to address
      the consequences of anthropogenic climate change. To support statewide climate
      change adaptation, we developed a framework for assessing climate change
      vulnerability of California's at-risk birds and integrating it into the existing
      California Bird Species of Special Concern list. We defined climate vulnerability
      as the amount of evidence that climate change will negatively impact a
      population. We quantified climate vulnerability by scoring sensitivity (intrinsic
      characteristics of an organism that make it vulnerable) and exposure (the
      magnitude of climate change expected) for each taxon. Using the combined
      sensitivity and exposure scores as an index, we ranked 358 avian taxa, and
      classified 128 as vulnerable to climate change. Birds associated with wetlands
      had the largest representation on the list relative to other habitat groups. Of
      the 29 state or federally listed taxa, 21 were also classified as climate
      vulnerable, further raising their conservation concern. Integrating climate
      vulnerability and California's Bird Species of Special Concern list resulted in
      the addition of five taxa and an increase in priority rank for ten. Our process
      illustrates a simple, immediate action that can be taken to inform climate change
      adaptation strategies for wildlife.

PMID- 22396725
TI  - Modeling and simulation of aggregation of membrane protein LAT with molecular
      variability in the number of binding sites for cytosolic Grb2-SOS1-Grb2.
AB  - The linker for activation of T cells (LAT), the linker for activation of B cells
      (LAB), and the linker for activation of X cells (LAX) form a family of
      transmembrane adaptor proteins widely expressed in lymphocytes. These scaffolding
      proteins have multiple binding motifs that, when phosphorylated, bind the SH2
      domain of the cytosolic adaptor Grb2. Thus, the valence of LAT, LAB and LAX for
      Grb2 is variable, depending on the strength of receptor activation that initiates
      phosphorylation. During signaling, the LAT population will exhibit a time-varying
      distribution of Grb2 valences from zero to three. In the cytosol, Grb2 forms 1:1
      and 2:1 complexes with the guanine nucleotide exchange factor SOS1. The 2:1
      complex can bridge two LAT molecules when each Grb2, through their SH2 domains,
      binds to a phosphorylated site on a separate LAT. In T cells and mast cells,
      after receptor engagement, receptor phosphoyrlation is rapidly followed by LAT
      phosphorylation and aggregation. In mast cells, aggregates containing more than
      one hundred LAT molecules have been detected. Previously we considered a
      homogeneous population of trivalent LAT molecules and showed that for a range of
      Grb2, SOS1 and LAT concentrations, an equilibrium theory for LAT aggregation
      predicts the formation of a gel-like phase comprising a very large aggregate
      (superaggregate). We now extend this theory to investigate the effects of a
      distribution of Grb2 valence in the LAT population on the formation of LAT
      aggregates and superaggregate and use stochastic simulations to calculate the
      fraction of the total LAT population in the superaggregate.

PMID- 22396727
TI  - Innate immune response of human alveolar macrophages during influenza A
      infection.
AB  - Alveolar macrophages (AM) are one of the key cell types for initiating
      inflammatory and immune responses to influenza virus in the lung. However, the
      genome-wide changes in response to influenza infection in AM have not been
      defined. We performed gene profiling of human AM in response to H1N1 influenza A
      virus PR/8 using Affymetrix HG-U133 Plus 2.0 chips and verified the changes at
      both mRNA and protein levels by real-time RT-PCR and ELISA. We confirmed the
      response with a contemporary H3N2 influenza virus A/New York/238/2005 (NY/238).
      To understand the local cellular response, we also evaluated the impact of
      paracrine factors on virus-induced chemokine and cytokine secretion. In addition,
      we investigated the changes in the expression of macrophage receptors and uptake
      of pathogens after PR/8 infection. Although macrophages fail to release a large
      amount of infectious virus, we observed a robust induction of type I and type III
      interferons and several cytokines and chemokines following influenza infection.
      CXCL9, 10, and 11 were the most highly induced chemokines by influenza infection.
      UV-inactivation abolished virus-induced cytokine and chemokine response, with the
      exception of CXCL10. The contemporary influenza virus NY/238 infection of AM
      induced a similar response as PR/8. Inhibition of TNF and/or IL-1beta activity
      significantly decreased the secretion of the proinflammatory chemokines CCL5 and
      CXCL8 by over 50%. PR/8 infection also significantly decreased mRNA levels of
      macrophage receptors including C-type lectin domain family 7 member A (CLEC7A),
      macrophage scavenger receptor 1 (MSR1), and CD36, and reduced uptake of zymosan.
      In conclusion, influenza infection induced an extensive proinflammatory response
      in human AM. Targeting local components of innate immune response might provide a
      strategy for controlling influenza A infection-induced proinflammatory response
      in vivo.

PMID- 22396728
TI  - Rapid screening for entry inhibitors of highly pathogenic viruses under low-level
      biocontainment.
AB  - Emerging viruses including Nipah, Hendra, Lujo, and Junin viruses have enormous
      potential to spread rapidly. Nipah virus, after emerging as a zoonosis, has also
      evolved the capacity for human-to-human transmission. Most of the diseases caused
      by these pathogens are untreatable and require high biocontainment conditions.
      Universal methods for rapidly identifying and screening candidate antivirals are
      urgently needed. We have developed a modular antiviral platform strategy that
      relies on simple bioinformatic and genetic information about each pathogen.
      Central to this platform is the use of envelope glycoprotein cDNAs to establish
      multi-cycle replication systems under BSL2 conditions for viral pathogens that
      normally require BSL3 and BSL4 facilities. We generated monoclonal antibodies
      against Nipah G by cDNA immunization in rats, and we showed that these antibodies
      neutralize both Nipah and Hendra live viruses. We then used these effective
      Henipavirus inhibitors to validate our screening strategy. Our proposed strategy
      should contribute to the response capability for emerging infectious diseases,
      providing a way to initiate antiviral development immediately upon identifying
      novel viruses.

PMID- 22396729
TI  - Transitions from injection-drug-use-concentrated to self-sustaining heterosexual
      HIV epidemics: patterns in the international data.
AB  - BACKGROUND: Injecting drug use continues to be a primary driver of HIV epidemics
      in many parts of the world. Many people who inject drugs (PWID) are sexually
      active, so it is possible that high-seroprevalence HIV epidemics among PWID may
      initiate self-sustaining heterosexual transmission epidemics. METHODS: Fourteen
      countries that had experienced high seroprevalence (<20%) HIV epidemics among
      PWID and had reliable data for injection drug use (IDU) and heterosexual cases of
      HIV or AIDS were identified. Graphs of newly reported HIV or AIDS cases among
      PWID and heterosexuals were constructed to identify temporal relationships
      between the two types of epidemics. The year in which newly reported cases among
      heterosexuals surpassed newly reported cases among PWID, aspects of the epidemic
      curves, and epidemic case histories were analyzed to assess whether it was
      "plausible" or "highly unlikely" that the HIV epidemic among PWID might have
      initiated the heterosexual epidemic in each country. RESULTS: Transitions have
      occurred in 11 of the 14 countries. Two types of temporal relationships between
      IDU and heterosexual HIV epidemics were identified, rapid high incidence
      transitions vs. delayed, low incidence transitions. In six countries it appears
      "plausible" that the IDU epidemic initiated a heterosexual epidemic, and in five
      countries it appears "highly unlikely" that the IDU epidemic initiated a
      heterosexual epidemic. A rapid decline in incidence among PWID after the peak
      year of new cases and national income were the best predictors of the "highly
      unlikely" initiation of a heterosexual epidemic. DISCUSSION: Transitions from IDU
      concentrated epidemics to heterosexual epidemics are common in countries with
      high seroprevalence among PWID though there are distinct types of transitions.
      Interventions to immediately reduce HIV incidence among PWID may reduce the
      likelihood that an IDU epidemic may initiate a heterosexual epidemic.

PMID- 22396730
TI  - No association of PTPN22 polymorphisms with susceptibility to ocular Behcet's
      disease in two Chinese Han populations.
AB  - BACKGROUND: Behcet's disease is known as a recurrent, multisystem inflammation
      and immune-related disease. Protein tyrosine phosphatase non-receptor 22 (PTPN22)
      is a key negative regulator of T lymphocytes and polymorphisms of the PTPN22 gene
      have been shown to be associated with various immune-related diseases. The
      present study was performed to assess the association between PTPN22
      polymorphisms and Behcet's disease in two Chinese Han populations.
      METHODOLOGY/PRINCIPAL FINDINGS: A total of 516 patients with ocular Behcet's
      disease and 690 healthy controls from two Chinese Han populations were genotyped
      by the polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) method for three single nucleotide polymorphisms (SNPs). Hardy-Weinberg
      equilibrium was tested using the chi(2) test. Genotype frequencies were estimated
      through direct counting. Allele and genotype frequencies were compared between
      patients and controls using logistic regression analysis. The results revealed
      that there was no association between the tested three PTPN22 SNPs (rs2488457,
      rs1310182 and rs3789604) and ocular Behcet's disease (p>0.05). Categorization
      analysis according to the clinical features did not show any association of these
      three polymorphisms with these parameters (p>0.05). CONCLUSIONS/SIGNIFICANCE: The
      investigated PTPN22 gene polymorphisms (rs2488457, rs1310182 and rs3789604) were
      not associated with ocular Behcet's disease in two Chinese Han populations, and
      showed that it may be different from other classical autoimmune diseases. More
      studies are needed to confirm these findings for Behcet's disease in other ethnic
      backgrounds.

PMID- 22396732
TI  - Cancer gene prioritization for targeted resequencing using FitSNP scores.
AB  - BACKGROUND: Although the throughput of next generation sequencing is increasing
      and at the same time the cost is substantially reduced, for the majority of
      laboratories whole genome sequencing of large cohorts of cancer samples is still
      not feasible. In addition, the low number of genomes that are being sequenced is
      often problematic for the downstream interpretation of the significance of the
      variants. Targeted resequencing can partially circumvent this problem; by
      focusing on a limited number of candidate cancer genes to sequence, more samples
      can be included in the screening, hence resulting in substantial improvement of
      the statistical power. In this study, a successful strategy for prioritizing
      candidate genes for targeted resequencing of cancer genomes is presented.
      RESULTS: Four prioritization strategies were evaluated on six different cancer
      types: genes were ranked using these strategies, and the positive predictive
      value (PPV) or mutation rate within the top-ranked genes was compared to the
      baseline mutation rate in each tumor type. Successful strategies generate gene
      lists in which the top is enriched for known mutated genes, as evidenced by an
      increase in PPV. A clear example of such an improvement is seen in colon cancer,
      where the PPV is increased by 2.3 fold compared to the baseline level when 100
      top fitSNP genes are sequenced. CONCLUSIONS: A gene prioritization strategy based
      on the fitSNP scores appears to be most successful in identifying mutated cancer
      genes across different tumor entities, with variance of gene expression levels as
      a good second best.

PMID- 22396731
TI  - Pretransplant prediction of posttransplant survival for liver recipients with
      benign end-stage liver diseases: a nonlinear model.
AB  - BACKGROUND: The scarcity of grafts available necessitates a system that considers
      expected posttransplant survival, in addition to pretransplant mortality as
      estimated by the MELD. So far, however, conventional linear techniques have
      failed to achieve sufficient accuracy in posttransplant outcome prediction. In
      this study, we aim to develop a pretransplant predictive model for liver
      recipients' survival with benign end-stage liver diseases (BESLD) by a nonlinear
      method based on pretransplant characteristics, and compare its performance with a
      BESLD-specific prognostic model (MELD) and a general-illness severity model (the
      sequential organ failure assessment score, or SOFA score). METHODOLOGY/PRINCIPAL
      FINDINGS: With retrospectively collected data on 360 recipients receiving
      deceased-donor transplantation for BESLD between February 1999 and August 2009 in
      the west China hospital of Sichuan university, we developed a multi-layer
      perceptron (MLP) network to predict one-year and two-year survival probability
      after transplantation. The performances of the MLP, SOFA, and MELD were assessed
      by measuring both calibration ability and discriminative power, with Hosmer
      Lemeshow test and receiver operating characteristic analysis, respectively. By
      the forward stepwise selection, donor age and BMI; serum concentration of HB,
      Crea, ALB, TB, ALT, INR, Na(+); presence of pretransplant diabetes; dialysis
      prior to transplantation, and microbiologically proven sepsis were identified to
      be the optimal input features. The MLP, employing 18 input neurons and 12 hidden
      neurons, yielded high predictive accuracy, with c-statistic of 0.91 (P<0.001) in
      one-year and 0.88 (P<0.001) in two-year prediction. The performances of SOFA and
      MELD were fairly poor in prognostic assessment, with c-statistics of 0.70 and
      0.66, respectively, in one-year prediction, and 0.67 and 0.65 in two-year
      prediction. CONCLUSIONS/SIGNIFICANCE: The posttransplant prognosis is a
      multidimensional nonlinear problem, and the MLP can achieve significantly high
      accuracy than SOFA and MELD scores in posttransplant survival prediction. The
      pattern recognition methodologies like MLP hold promise for solving
      posttransplant outcome prediction.

PMID- 22396733
TI  - The Fynbos and sUcculent Karoo biomes do not have exceptional local ant richness.
AB  - BACKGROUND: The Fynbos (FB) and Succulent Karoo biomes (SKB) have high regional
      plant diversity despite relatively low productivity. Local diversity in the
      region varies but is moderate. For insects, previous work suggests that strict
      phytophages, but not other taxa, may have high regional richness. However, what
      has yet to be investigated is whether the local insect species richness of FB and
      SKB is unusual for a region of this productivity level at this latitude, and
      whether regional richness is also high. Here we determine whether this is the
      case for ants. METHODOLOGY/PRINCIPAL FINDINGS: We use species richness data from
      pitfall traps in the FB and SKB in the Western Cape Province, South Africa and a
      global dataset of local ant richness extracted from the literature. We then
      relate the globally derived values of local richness to two energy-related
      predictors--productive energy (NDVI) and temperature, and to precipitation, and
      compare the data from the FB and SKB with these relationships. We further compare
      our local richness estimates with that of similar habitats worldwide, and
      regional ant richness with estimates derived from other regions. The local ant
      species richness of the FB and SKB falls within the general global pattern
      relating ant richness to energy, and is similar to that in comparable habitats
      elsewhere. At a regional scale, the richness of ants across all of our sites is
      not exceptional by comparison with other regional estimates from across the
      globe. CONCLUSIONS/SIGNIFICANCE: Local richness of ants in the FB and SKB is not
      exceptional by global standards. Initial analyses suggest that regional diversity
      is also not exceptional for the group. It seems unlikely that the mechanisms
      which have contributed to the development of extraordinarily high regional plant
      diversity in these biomes have had a strong influence on the ants.

PMID- 22396734
TI  - Mapping and functional characterisation of a CTCF-dependent insulator element at
      the 3' border of the murine Scl transcriptional domain.
AB  - The Scl gene encodes a transcription factor essential for haematopoietic
      development. Scl transcription is regulated by a panel of cis-elements spread
      over 55 kb with the most distal 3' element being located downstream of the
      neighbouring gene Map17, which is co-regulated with Scl in haematopoietic cells.
      The Scl/Map17 domain is flanked upstream by the ubiquitously expressed Sil gene
      and downstream by a cluster of Cyp genes active in liver, but the mechanisms
      responsible for delineating the domain boundaries remain unclear. Here we report
      identification of a DNaseI hypersensitive site at the 3' end of the Scl/Map17
      domain and 45 kb downstream of the Scl transcription start site. This element is
      located at the boundary of active and inactive chromatin, does not function as a
      classical tissue-specific enhancer, binds CTCF and is both necessary and
      sufficient for insulator function in haematopoietic cells in vitro. Moreover, in
      a transgenic reporter assay, tissue-specific expression of the Scl promoter in
      brain was increased by incorporation of 350 bp flanking fragments from the +45
      element. Our data suggests that the +45 region functions as a boundary element
      that separates the Scl/Map17 and Cyp transcriptional domains, and raise the
      possibility that this element may be useful for improving tissue-specific
      expression of transgenic constructs.

PMID- 22396735
TI  - Macro and micro diversity of Clostridium difficile isolates from diverse sources
      and geographical locations.
AB  - Clostridium difficile has emerged rapidly as the leading cause of antibiotic
      associated diarrheal disease, with the temporal and geographical appearance of
      dominant PCR ribotypes such as 017, 027 and 078. Despite this continued threat,
      we have a poor understanding of how or why particular variants emerge and the
      sources of strains that dominate different human populations. We have undertaken
      a breadth genotyping study using multilocus sequence typing (MLST) analysis of
      385 C. difficile strains from diverse sources by host (human, animal and food),
      geographical locations (North America, Europe and Australia) and PCR ribotypes.
      Results identified 18 novel sequence types (STs) and 3 new allele sequences and
      confirmed the presence of five distinct clonal lineages generally associated with
      outbreaks of C. difficile infection in humans. Strains of animal and food origin
      were found of both ST-1 and ST-11 that are frequently associated with human
      disease. An in depth MLST analysis of the evolutionary distant ST-11/PCR ribotype
      078 clonal lineage revealed that ST-11 can be found in alternative but closely
      related PCR ribotypes and PCR ribotype 078 alleles contain mutations generating
      novel STs. PCR ribotype 027 and 017 lineages may consist of two divergent
      subclades. Furthermore evidence of microdiversity was present within the
      heterogeneous clade 1. This study helps to define the evolutionary origin of
      dominant C. difficile lineages and demonstrates that C. difficile is continuing
      to evolve in concert with human activity.

PMID- 22396736
TI  - A method for generation phage cocktail with great therapeutic potential.
AB  - BACKGROUND: Bacteriophage could be an alternative to conventional antibiotic
      therapy against multidrug-resistant bacteria. However, the emergence of resistant
      variants after phage treatment limited its therapeutic application.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, an approach, named "Step-by-Step"
      (SBS), has been established. This method takes advantage of the occurrence of
      phage-resistant bacteria variants and ensures that phages lytic for wild-type
      strain and its phage-resistant variants are selected. A phage cocktail lytic for
      Klebsiella pneumoniae was established by the SBS method. This phage cocktail
      consisted of three phages (GH-K1, GH-K2 and GH-K3) which have different but
      overlapping host strains. Several phage-resistant variants of Klebsiella
      pneumoniae were isolated after different phages treatments. The virulence of
      these variants was much weaker [minimal lethal doses (MLD)>1.3*10(9) cfu/mouse]
      than that of wild-type K7 countpart (MLD = 2.5*10(3) cfu/mouse). Compared with
      any single phage, the phage cocktail significantly reduced the mutation frequency
      of Klebsiella pneumoniae and effectively rescued Klebsiella pneumoniae bacteremia
      in a murine K7 strain challenge model. The minimal protective dose (MPD) of the
      phage cocktail which was sufficient to protect bacteremic mice from lethal K7
      infection was only 3.0*10(4) pfu, significantly smaller (p<0.01) than that of
      single monophage. Moreover, a delayed administration of this phage cocktail was
      still effective in protection against K7 challenge. CONCLUSIONS/SIGNIFICANCE: Our
      data showed that the phage cocktail was more effective in reducing bacterial
      mutation frequency and in the rescue of murine bacteremia than monophage
      suggesting that phage cocktail established by SBS method has great therapeutic
      potential for multidrug-resistant bacteria infection.

PMID- 22396737
TI  - Glucocorticoid-induced leucine zipper (GILZ) antagonizes TNF-alpha inhibition of
      mesenchymal stem cell osteogenic differentiation.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a potent proinflammatory cytokine that
      inhibits osteoblast differentiation while stimulating osteoclast differentiation
      and bone resorption. TNF-alpha activates MAP kinase pathway leading to inhibition
      of osterix (Osx) expression. TNF-alpha also induces the expression of E3
      ubiquitin ligase protein Smurf1 and Smurf2 and promotes degradation of Runx2,
      another key transcription factor regulating osteoblast differentiation and bone
      formation. We showed previously that overexpression of glucocorticoid (GC)
      induced leucine zipper (GILZ) enhances osteogenic differentiation of bone marrow
      mesenchymal stem cells (MSCs). We and others also showed that GILZ is a GC
      effecter and mediates GC anti-inflammatory activity. In this study, we asked the
      question whether GILZ retains its osteogenic activity while functioning as an
      anti-inflammatory mediator. To address this question, we infected mouse bone
      marrow MSCs with retroviruses expressing GILZ and induced them for osteogenic
      differentiation in the presence or absence of TNF-alpha. Our results show that
      overexpression of GILZ antagonized the inhibitory effects of TNF-alpha on MSC
      osteogenic differentiation and the mRNA and protein expression of Osx and Runx2,
      two pivotal osteogenic regulators. Further studies show that these antagonistic
      actions occur via mechanisms involving GILZ inhibition of TNF-alpha-induced ERK
      MAP kinase activation and protein degradation. These results suggest that GILZ
      may have therapeutic potential as a novel anti-inflammation therapy.

PMID- 22396738
TI  - Variation of maximum tree height and annual shoot growth of Smith fir at various
      elevations in the Sygera Mountains, southeastern Tibetan Plateau.
AB  - Little is known about tree height and height growth (as annual shoot elongation
      of the apical part of vertical stems) of coniferous trees growing at various
      altitudes on the Tibetan Plateau, which provides a high-elevation natural
      platform for assessing tree growth performance in relation to future climate
      change. We here investigated the variation of maximum tree height and annual
      height increment of Smith fir (Abies georgei var. smithii) in seven forest plots
      (30 m*40 m) along two altitudinal transects between 3,800 m and 4,200/4,390 m
      above sea level (a.s.l.) in the Sygera Mountains, southeastern Tibetan Plateau.
      Four plots were located on north-facing slopes and three plots on southeast
      facing slopes. At each site, annual shoot growth was obtained by measuring the
      distance between successive terminal bud scars along the main stem of 25 trees
      that were between 2 and 4 m high. Maximum/mean tree height and mean annual height
      increment of Smith fir decreased with increasing altitude up to the tree line,
      indicative of a stress gradient (the dominant temperature gradient) along the
      altitudinal transect. Above-average mean minimum summer (particularly July)
      temperatures affected height increment positively, whereas precipitation had no
      significant effect on shoot growth. The time series of annual height increments
      of Smith fir can be used for the reconstruction of past climate on the
      southeastern Tibetan Plateau. In addition, it can be expected that the rising
      summer temperatures observed in the recent past and anticipated for the future
      will enhance Smith fir's growth throughout its altitudinal distribution range.

PMID- 22396739
TI  - New model of macrophage acquisition of the lymphatic endothelial phenotype.
AB  - BACKGROUND: Macrophage-derived lymphatic endothelial cell progenitors (M-LECPs)
      contribute to new lymphatic vessel formation, but the mechanisms regulating their
      differentiation, recruitment, and function are poorly understood. Detailed
      characterization of M-LECPs is limited by low frequency in vivo and lack of model
      systems allowing in-depth molecular analyses in vitro. Our goal was to establish
      a cell culture model to characterize inflammation-induced macrophage-to-LECP
      differentiation under controlled conditions. METHODOLOGY/PRINCIPAL FINDINGS: Time
      course analysis of diaphragms from lipopolysaccharide (LPS)-treated mice revealed
      rapid mobilization of bone marrow-derived and peritoneal macrophages to the
      proximity of lymphatic vessels followed by widespread (~50%) incorporation of M
      LECPs into the inflamed lymphatic vasculature. A differentiation shift toward the
      lymphatic phenotype was found in three LPS-induced subsets of activated
      macrophages that were positive for VEGFR-3 and many other lymphatic-specific
      markers. VEGFR-3 was strongly elevated in the early stage of macrophage
      transition to LECPs but undetectable in M-LECPs prior to vascular integration.
      Similar transient pattern of VEGFR-3 expression was found in RAW264.7 macrophages
      activated by LPS in vitro. Activated RAW264.7 cells co-expressed VEGF-C that
      induced an autocrine signaling loop as indicated by VEGFR-3 phosphorylation
      inhibited by a soluble receptor. LPS-activated RAW264.7 macrophages also showed a
      68% overlap with endogenous CD11b(+)/VEGFR-3(+) LECPs in the expression of
      lymphatic-specific genes. Moreover, when injected into LPS- but not saline
      treated mice, GFP-tagged RAW264.7 cells massively infiltrated the inflamed
      diaphragm followed by integration into 18% of lymphatic vessels.
      CONCLUSIONS/SIGNIFICANCE: We present a new model for macrophage-LECP
      differentiation based on LPS activation of cultured RAW264.7 cells. This system
      designated here as the "RAW model" mimics fundamental features of endogenous M
      LECPs. Unlike native LECPs, this model is unrestricted by cell numbers,
      heterogeneity of population, and ability to change genetic composition for
      experimental purposes. As such, this model can provide a valuable tool for
      understanding the LECP and lymphatic biology.

PMID- 22396740
TI  - Triazole fungicides can induce cross-resistance to medical triazoles in
      Aspergillus fumigatus.
AB  - BACKGROUND: Azoles play an important role in the management of Aspergillus
      diseases. Azole resistance is an emerging global problem in Aspergillus
      fumigatus, and may develop through patient therapy. In addition, an environmental
      route of resistance development has been suggested through exposure to 14alpha
      demethylase inhibitors (DMIs). The main resistance mechanism associated with this
      putative fungicide-driven route is a combination of alterations in the Cyp51A
      gene (TR(34)/L98H). We investigated if TR(34)/L98H could have developed through
      exposure to DMIs. METHODS AND FINDINGS: Thirty-one compounds that have been
      authorized for use as fungicides, herbicides, herbicide safeners and plant growth
      regulators in The Netherlands between 1970 and 2005, were investigated for cross
      resistance to medical triazoles. Furthermore, CYP51-protein homology modeling and
      molecule alignment studies were performed to identify similarity in molecule
      structure and docking modes. Five triazole DMIs, propiconazole, bromuconazole,
      tebuconazole, epoxiconazole and difenoconazole, showed very similar molecule
      structures to the medical triazoles and adopted similar poses while docking the
      protein. These DMIs also showed the greatest cross-resistance and, importantly,
      were authorized for use between 1990 and 1996, directly preceding the recovery of
      the first clinical TR(34)/L98H isolate in 1998. Through microsatellite genotyping
      of TR(34)/L98H isolates we were able to calculate that the first isolate would
      have arisen in 1997, confirming the results of the abovementioned experiments.
      Finally, we performed induction experiments to investigate if TR(34)/L98H could
      be induced under laboratory conditions. One isolate evolved from two copies of
      the tandem repeat to three, indicating that fungicide pressure can indeed result
      in these genomic changes. CONCLUSIONS: Our findings support a fungicide-driven
      route of TR(34)/L98H development in A. fumigatus. Similar molecule structure
      characteristics of five triazole DMIs and the three medical triazoles appear the
      underlying mechanism of cross resistance development. Our findings have major
      implications for the assessment of health risks associated with the use of
      triazole DMIs.

PMID- 22396741
TI  - Common variants of the liver fatty acid binding protein gene influence the risk
      of type 2 diabetes and insulin resistance in Spanish population.
AB  - SUMMARY: The main objective was to evaluate the association between SNPs and
      haplotypes of the FABP1-4 genes and type 2 diabetes, as well as its interaction
      with fat intake, in one general Spanish population. The association was
      replicated in a second population in which HOMA index was also evaluated.
      METHODS: 1217 unrelated individuals were selected from a population-based study
      [Hortega study: 605 women; mean age 54 y; 7.8% with type 2 diabetes]. The
      replication population included 805 subjects from Segovia, a neighboring region
      of Spain (446 females; mean age 52 y; 10.3% with type 2 diabetes). DM2 mellitus
      was defined in a similar way in both studies. Fifteen SNPs previously associated
      with metabolic traits or with potential influence in the gene expression within
      the FABP1-4 genes were genotyped with SNPlex and tested. Age, sex and BMI were
      used as covariates in the logistic regression model. RESULTS: One polymorphism
      (rs2197076) and two haplotypes of the FABP-1 showed a strong association with the
      risk of DM2 in the original population. This association was further confirmed in
      the second population as well as in the pooled sample. None of the other analyzed
      variants in FABP2, FABP3 and FABP4 genes were associated. There was not a formal
      interaction between rs2197076 and fat intake. A significant association between
      the rs2197076 and the haplotypes of the FABP1 and HOMA-IR was also present in the
      replication population. CONCLUSIONS: The study supports the role of common
      variants of the FABP-1 gene in the development of type 2 diabetes in Caucasians.

PMID- 22396742
TI  - MiR-194 regulates chondrogenic differentiation of human adipose-derived stem
      cells by targeting Sox5.
AB  - Osteoarthritis, also known as degenerative arthritis or degenerative joint
      disease, causes pain and disability worldwide. Cartilage regeneration is key to
      finding a cure for this disease. Adipose-derived stem cells (ASCs) are capable of
      differentiating into cartilage lineages in vitro and they have shown promise in
      the field of regenerative medicine. However, the underlying mechanisms remain
      unclear. In this study, we demonstrated that miR-194 levels gradually decreased
      during the chondrogenic differentiation of human ASCs (hASCs). After predicting
      the target of miR-194 using Pictar and Targetscan, we hypothesized that Sox5 is
      potentially the key link between miR-194 and the chondrogenesis of ASCs.
      Initially, we demonstrated that Sox5 is a target of miR194 according to
      luciferase assay analysis. We further demonstrated that the differentiation of
      ASCs can be controlled by miR-194 through gain or loss of function experiments,
      and we observed that the down-regulation of miR-194 increases its direct target
      gene, Sox5, and results in enhanced chondrogenic differentiation of hASCs,
      whereas up-regulation decreases Sox5 and inhibits chondrogenesis. We also found
      that miR-194 correlates with Sox5 in osteoarthritis. These findings, taken
      together, are the first to illustrate the critical role of miR-194 in hASC
      chondrogenesis, and may provide novel insight beneficial to cell manipulation
      methods during cartilage regeneration.

PMID- 22396743
TI  - Smoking dose modifies the association between C242T polymorphism and prevalence
      of metabolic syndrome in a Chinese population.
AB  - BACKGROUND: The C242T polymorphism of the CYBA gene that encodes p22phox, a
      component of NADPH oxidase, has been found to modulate superoxide production.
      Oxidase is a major source of the superoxide anion that contributes to individual
      components of metabolic syndrome. We examined the relationship of the C242T
      polymorphism with the prevalence of metabolic syndrome in a Chinese population,
      taking account of consumed cigarette amounts. METHODOLOGY/PRINCIPAL FINDINGS: In
      870 participants, we collected biomarkers related to metabolic syndrome and
      detailed history of smoking and genotyped the C242T polymorphisms. After
      adjustment for covariates, the CT/TT genotypes were associated with a lower risk
      of metabolic syndrome (P = 0.0008). The odds of having metabolic syndrome in the
      CT/TT participants were 0.439 (95%CI: 0.265, 0.726), while for CC participants
      the odds were 1.110 (95%CI: 0.904, 1.362). There was significant (P = 0.014)
      interaction between the C242T polymorphism and smoking status in relation to the
      prevalence of metabolic syndrome. For smokers who smoke no less than 25 pack
      years, those with CT/TT genotypes had lower risk of metabolic syndrome as
      compared with CC polymorphism carriers (P = 0.015). In the multiple regression
      analysis, the CT/TT genotypes were significantly associated with lower serum
      concentration of triglycerides both in all subjects and smokers; furthermore, the
      CT/TT genotypes were also related to smaller waist circumference in smokers.
      CONCLUSIONS: Our study suggests that the C242T gene polymorphism is indeed
      related to the prevalence of metabolic syndrome and smoking dose might modify
      this association.

PMID- 22396744
TI  - Global diversity of brittle stars (Echinodermata: Ophiuroidea).
AB  - This review presents a comprehensive overview of the current status regarding the
      global diversity of the echinoderm class Ophiuroidea, focussing on taxonomy and
      distribution patterns, with brief introduction to their anatomy, biology,
      phylogeny, and palaeontological history. A glossary of terms is provided. Species
      names and taxonomic decisions have been extracted from the literature and
      compiled in The World Ophiuroidea Database, part of the World Register of Marine
      Species (WoRMS). Ophiuroidea, with 2064 known species, are the largest class of
      Echinodermata. A table presents 16 families with numbers of genera and species.
      The largest are Amphiuridae (467), Ophiuridae (344 species) and Ophiacanthidae
      (319 species). A biogeographic analysis for all world oceans and all accepted
      species was performed, based on published distribution records. Approximately
      similar numbers of species were recorded from the shelf (n = 1313) and bathyal
      depth strata (1297). The Indo-Pacific region had the highest species richness
      overall (825 species) and at all depths. Adjacent regions were also relatively
      species rich, including the North Pacific (398), South Pacific (355) and Indian
      (316) due to the presence of many Indo-Pacific species that partially extended
      into these regions. A secondary region of enhanced species richness was found in
      the West Atlantic (335). Regions of relatively low species richness include the
      Arctic (73 species), East Atlantic (118), South America (124) and Antarctic
      (126).

PMID- 22396745
TI  - Switching virally suppressed, treatment-experienced patients to a raltegravir
      containing regimen does not alter levels of HIV-1 DNA.
AB  - BACKGROUND: Current HIV-1 antiretroviral therapy (ART) greatly reduces virus
      replication but does not significantly affect the viral reservoir. Raltegravir, a
      recently introduced integrase inhibitor, could, at least theoretically, reduce
      residual viremia in patients on ART and affect the viral reservoir size. The aim
      of this study was to assess whether switching therapy in treatment-experienced
      patients that were virally suppressed to a raltegravir-containing regimen reduces
      the size of the viral reservoir, and if such treatment leads to a change in
      levels of HIV 2-LTR circles in this patient group. METHODS: 14 ART experienced
      individuals with a suppressed viral load (<50 HIV-1 RNA copies/mL plasma) at
      baseline (for at least 2 months) were switched to a raltegravir-containing
      regimen. Blood samples were taken at baseline and at >=2 timepoints up to 48+/-6
      weeks. Levels of total HIV-1 DNA and 2-LTR circles in peripheral blood
      mononuclear cells (PBMCs) were measured using real-time PCR assays. RESULTS:
      There was no significant change in HIV-1 total DNA levels over the study duration
      (p = 0.808), median slope 0.24 (conservative nonparametric 95% CI: -11.78,
      26.23). Low levels of 2-LTR circles were detected in 2 patients. One had 16
      copies/10(6) PBMCs at baseline and the other had 34 copies/10(6) PBMCs at week
      51. CONCLUSIONS: The switch to a raltegravir containing regimen was not
      associated with a significant change in HIV-1 total DNA levels in this cohort.
      There were no observed changes in the levels of HIV-1 2-LTR circles associated
      with raltegravir treatment initiation.

PMID- 22396747
TI  - Isolation and characterization of EstC, a new cold-active esterase from
      Streptomyces coelicolor A3(2).
AB  - The genome sequence of Streptomyces coelicolor A3(2) contains more than 50 genes
      coding for putative lipolytic enzymes. Many studies have shown the capacity of
      this actinomycete to store important reserves of intracellular triacylglycerols
      in nutrient depletion situations. In the present study, we used genome mining of
      S. coelicolor to identify genes coding for putative, non-secreted
      esterases/lipases. Two genes were cloned and successfully overexpressed in E.
      coli as His-tagged fusion proteins. One of the recombinant enzymes, EstC, showed
      interesting cold-active esterase activity with a strong potential for the
      production of valuable esters. The purified enzyme displayed optimal activity at
      35 degrees C and was cold-active with retention of 25% relative activity at 10
      degrees C. Its optimal pH was 8.5-9 but the enzyme kept more than 75% of its
      maximal activity between pH 7.5 and 10. EstC also showed remarkable tolerance
      over a wide range of pH values, retaining almost full residual activity between
      pH 6-11. The enzyme was active toward short-chain p-nitrophenyl esters (C2-C12),
      displaying optimal activity with the valerate (C5) ester (k(cat)/K(m) = 737+/-77
      s(-1) mM(-1)). The enzyme was also very active toward short chain triglycerides
      such as triacetin (C2:0) and tributyrin (C4:0), in addition to showing good
      primary alcohol and organic solvent tolerance, suggesting it could function as an
      interesting candidate for organic synthesis of short-chain esters such as
      flavors.

PMID- 22396746
TI  - Rapid and accurate prediction and scoring of water molecules in protein binding
      sites.
AB  - Water plays a critical role in ligand-protein interactions. However, it is still
      challenging to predict accurately not only where water molecules prefer to bind,
      but also which of those water molecules might be displaceable. The latter is
      often seen as a route to optimizing affinity of potential drug candidates. Using
      a protocol we call WaterDock, we show that the freely available AutoDock Vina
      tool can be used to predict accurately the binding sites of water molecules.
      WaterDock was validated using data from X-ray crystallography, neutron
      diffraction and molecular dynamics simulations and correctly predicted 97% of the
      water molecules in the test set. In addition, we combined data-mining, heuristic
      and machine learning techniques to develop probabilistic water molecule
      classifiers. When applied to WaterDock predictions in the Astex Diverse Set of
      protein ligand complexes, we could identify whether a water molecule was
      conserved or displaced to an accuracy of 75%. A second model predicted whether
      water molecules were displaced by polar groups or by non-polar groups to an
      accuracy of 80%. These results should prove useful for anyone wishing to
      undertake rational design of new compounds where the displacement of water
      molecules is being considered as a route to improved affinity.

PMID- 22396748
TI  - Preparation of mouse monoclonal antibody for RB1CC1 and its clinical application.
AB  - RB1-inducible coiled-coil 1 (RB1CC1; also known as FIP200) plays important roles
      in several biological pathways such as cell proliferation and autophagy.
      Evaluation of RB1CC1 expression can provide useful clinical information on
      various cancers and neurodegenerative diseases. In order to realize the clinical
      applications, it is necessary to establish a stable supply of antibody and
      reproducible procedures for the laboratory examinations. In the present study, we
      have generated mouse monoclonal antibodies for RB1CC1, and four kinds of
      antibodies (N1-8, N1-216, N3-2, and N3-42) were found to be optimal for clinical
      applications such as ELISA and immunoblots and work as well as the pre-existing
      polyclonal antibodies. N1-8 monoclonal antibody provided the best recognition of
      RB1CC1 in the clinico-pathological examination of formalin-fixed paraffin
      embedded tissues. These monoclonal antibodies will help to generate new
      opportunities in scientific examinations in biology and clinical medicine.

PMID- 22396749
TI  - The influence of coastal access on isotope variation in Icelandic arctic foxes.
AB  - To quantify the ecological effects of predator populations, it is important to
      evaluate how population-level specializations are dictated by intra- versus inter
      individual dietary variation. Coastal habitats contain prey from the terrestrial
      biome, the marine biome and prey confined to the coastal region. Such habitats
      have therefore been suggested to better support predator populations compared to
      habitats without coastal access. We used stable isotope data on a small
      generalist predator, the arctic fox, to infer dietary strategies between adult
      and juvenile individuals with and without coastal access on Iceland. Our results
      suggest that foxes in coastal habitats exhibited a broader isotope niche breadth
      compared to foxes in inland habitats. This broader niche was related to a greater
      diversity of individual strategies rather than to a uniform increase in
      individual niche breadth or by individuals retaining their specialization but
      increasing their niche differentiation. Juveniles in coastal habitats exhibited a
      narrower isotope niche breadth compared to both adults and juveniles in inland
      habitats, and juveniles in inland habitats inhabited a lower proportion of their
      total isotope niche compared to adults and juveniles from coastal habitats.
      Juveniles in both habitats exhibited lower intra-individual variation compared to
      adults. Based on these results, we suggest that foxes in both habitats were
      highly selective with respect to the resources they used to feed offspring, but
      that foxes in coastal habitats preferentially utilized marine resources for this
      purpose. We stress that coastal habitats should be regarded as high priority
      areas for conservation of generalist predators as they appear to offer a wide
      variety of dietary options that allow for greater flexibility in dietary
      strategies.

PMID- 22396750
TI  - Deciphering CAPTCHAs: what a Turing test reveals about human cognition.
AB  - Turning Turing's logic on its head, we used widespread letter-based Turing Tests
      found on the internet (CAPTCHAs) to shed light on human cognition. We examined
      the basis of the human ability to solve CAPTCHAs, where machines fail. We asked
      whether this is due to our use of slow-acting inferential processes that would
      not be available to machines, or whether fast-acting automatic orthographic
      processing in humans has superior robustness to shape variations. A masked
      priming lexical decision experiment revealed efficient processing of CAPTCHA
      words in conditions that rule out the use of slow inferential processing. This
      shows that the human superiority in solving CAPTCHAs builds on a high degree of
      invariance to location and continuous transforms, which is achieved during the
      very early stages of visual word recognition in skilled readers.

PMID- 22396751
TI  - Glaciation effects on the phylogeographic structure of Oligoryzomys longicaudatus
      (Rodentia: Sigmodontinae) in the southern Andes.
AB  - The long-tailed pygmy rice rat Oligoryzomys longicaudatus (Sigmodontinae), the
      major reservoir of Hantavirus in Chile and Patagonian Argentina, is widely
      distributed in the Mediterranean, Temperate and Patagonian Forests of Chile, as
      well as in adjacent areas in southern Argentina. We used molecular data to
      evaluate the effects of the last glacial event on the phylogeographic structure
      of this species. We examined if historical Pleistocene events had affected
      genetic variation and spatial distribution of this species along its
      distributional range. We sampled 223 individuals representing 47 localities along
      the species range, and sequenced the hypervariable domain I of the mtDNA control
      region. Aligned sequences were analyzed using haplotype network, bayesian
      population structure and demographic analyses. Analysis of population structure
      and the haplotype network inferred three genetic clusters along the distribution
      of O. longicaudatus that mostly agreed with the three major ecogeographic regions
      in Chile: Mediterranean, Temperate Forests and Patagonian Forests. Bayesian
      Skyline Plots showed constant population sizes through time in all three clusters
      followed by an increase after and during the Last Glacial Maximum (LGM; between
      26,000-13,000 years ago). Neutrality tests and the "g" parameter also suggest
      that populations of O. longicaudatus experienced demographic expansion across the
      species entire range. Past climate shifts have influenced population structure
      and lineage variation of O. longicaudatus. This species remained in refugia areas
      during Pleistocene times in southern Temperate Forests (and adjacent areas in
      Patagonia). From these refugia, O. longicaudatus experienced demographic
      expansions into Patagonian Forests and central Mediterranean Chile using glacial
      retreats.

PMID- 22396752
TI  - Flavonoid glycosides isolated from unique legume plant extracts as novel
      inhibitors of xanthine oxidase.
AB  - Legumes and the polyphenolic compounds present in them have gained a lot of
      interest due to their beneficial health implications. Dietary polyphenolic
      compounds, especially flavonoids, exert antioxidant properties and are potent
      inhibitors of xanthine oxidase (XO) activity. XO is the main contributor of free
      radicals during exercise but it is also involved in pathogenesis of several
      diseases such as vascular disorders, cancer and gout. In order to discover new
      natural, dietary XO inhibitors, some polyphenolic fractions and pure compounds
      isolated from two legume plant extracts were tested for their effects on XO
      activity. The fractions isolated from both Vicia faba and Lotus edulis plant
      extracts were potent inhibitors of XO with IC(50) values range from 40-135 ug/mL
      and 55-260 ug/mL, respectively. All the pure polyphenolic compounds inhibited XO
      and their K(i) values ranged from 13-767 uM. Ten of the compounds followed the
      non competitive inhibitory model whereas one of them was a competitive inhibitor.
      These findings indicate that flavonoid isolates from legume plant extracts are
      novel, natural XO inhibitors. Their mode of action is under investigation in
      order to examine their potential in drug design for diseases related to
      overwhelming XO action.

PMID- 22396753
TI  - Neurofeedback using real-time near-infrared spectroscopy enhances motor imagery
      related cortical activation.
AB  - Accumulating evidence indicates that motor imagery and motor execution share
      common neural networks. Accordingly, mental practices in the form of motor
      imagery have been implemented in rehabilitation regimes of stroke patients with
      favorable results. Because direct monitoring of motor imagery is difficult,
      feedback of cortical activities related to motor imagery (neurofeedback) could
      help to enhance efficacy of mental practice with motor imagery. To determine the
      feasibility and efficacy of a real-time neurofeedback system mediated by near
      infrared spectroscopy (NIRS), two separate experiments were performed. Experiment
      1 was used in five subjects to evaluate whether real-time cortical oxygenated
      hemoglobin signal feedback during a motor execution task correlated with
      reference hemoglobin signals computed off-line. Results demonstrated that the
      NIRS-mediated neurofeedback system reliably detected oxygenated hemoglobin signal
      changes in real-time. In Experiment 2, 21 subjects performed motor imagery of
      finger movements with feedback from relevant cortical signals and irrelevant sham
      signals. Real neurofeedback induced significantly greater activation of the
      contralateral premotor cortex and greater self-assessment scores for kinesthetic
      motor imagery compared with sham feedback. These findings suggested the
      feasibility and potential effectiveness of a NIRS-mediated real-time
      neurofeedback system on performance of kinesthetic motor imagery. However, these
      results warrant further clinical trials to determine whether this system could
      enhance the effects of mental practice in stroke patients.

PMID- 22396754
TI  - Antifungal susceptibility profiles of 1698 yeast reference strains revealing
      potential emerging human pathogens.
AB  - New molecular identification techniques and the increased number of patients with
      various immune defects or underlying conditions lead to the emergence and/or the
      description of novel species of human and animal fungal opportunistic pathogens.
      Antifungal susceptibility provides important information for ecological,
      epidemiological and therapeutic issues. The aim of this study was to assess the
      potential risk of the various species based on their antifungal drug resistance,
      keeping in mind the methodological limitations. Antifungal susceptibility
      profiles to the five classes of antifungal drugs (polyens, azoles, echinocandins,
      allylamines and antimetabolites) were determined for 1698 yeast reference strains
      belonging to 992 species (634 Ascomycetes and 358 Basidiomycetes). Interestingly,
      geometric mean minimum inhibitory concentrations (MICs) of all antifungal drugs
      tested were significantly higher for Basidiomycetes compared to Ascomycetes
      (p<0.001). Twenty four strains belonging to 23 species of which 19 were
      Basidiomycetes seem to be intrinsically "resistant" to all drugs. Comparison of
      the antifungal susceptibility profiles of the 4240 clinical isolates and the 315
      reference strains belonging to 53 shared species showed similar results. Even in
      the absence of demonstrated in vitro/in vivo correlation, knowing the in vitro
      susceptibility to systemic antifungal agents and the putative intrinsic
      resistance of yeast species present in the environment is important because they
      could become opportunistic pathogens.

PMID- 22396755
TI  - Genomic regions associated with multiple sclerosis are active in B cells.
AB  - More than 50 genomic regions have now been shown to influence the risk of
      multiple sclerosis (MS). However, the mechanisms of action, and the cell types in
      which these associated variants act at the molecular level remain largely
      unknown. This is especially true for associated regions containing no known
      genes. Given the evidence for a role for B cells in MS, we hypothesized that MS
      associated genomic regions co-localized with regions which are functionally
      active in B cells. We used publicly available data on 1) MS associated regions
      and single nucleotide polymorphisms (SNPs) and 2) chromatin profiling in B cells
      as well as three additional cell types thought to be unrelated to MS
      (hepatocytes, fibroblasts and keratinocytes). Genomic intervals and SNPs were
      tested for overlap using the Genomic Hyperbrowser. We found that MS associated
      regions are significantly enriched in strong enhancer, active promoter and strong
      transcribed regions (p = 0.00005) and that this overlap is significantly higher
      in B cells than control cells. In addition, MS associated SNPs also land in
      active promoter (p = 0.00005) and enhancer regions more than expected by chance
      (strong enhancer p = 0.0006; weak enhancer p = 0.00005). These results confirm
      the important role of the immune system and specifically B cells in MS and
      suggest that MS risk variants exert a gene regulatory role. Previous studies
      assessing MS risk variants in T cells may be missing important effects in B
      cells. Similar analyses in other immunological cell types relevant to MS and
      functional studies are necessary to fully elucidate how genes contribute to MS
      pathogenesis.

PMID- 22396756
TI  - HIV epidemic appraisals for assisting in the design of effective prevention
      programmes: shifting the paradigm back to basics.
AB  - BACKGROUND: To design HIV prevention programmes, it is critical to understand the
      temporal and geographic aspects of the local epidemic and to address the key
      behaviours that drive HIV transmission. Two methods have been developed to
      appraise HIV epidemics and guide prevention strategies. The numerical proxy
      method classifies epidemics based on current HIV prevalence thresholds. The Modes
      of Transmission (MOT) model estimates the distribution of incidence over one year
      among risk-groups. Both methods focus on the current state of an epidemic and
      provide short-term metrics which may not capture the epidemiologic drivers.
      Through a detailed analysis of country and sub-national data, we explore the
      limitations of the two traditional methods and propose an alternative approach.
      METHODS AND FINDINGS: We compared outputs of the traditional methods in five
      countries for which results were published, and applied the numeric and MOT model
      to India and six districts within India. We discovered three limitations of the
      current methods for epidemic appraisal: (1) their results failed to identify the
      key behaviours that drive the epidemic; (2) they were difficult to apply to local
      epidemics with heterogeneity across district-level administrative units; and (3)
      the MOT model was highly sensitive to input parameters, many of which required
      extraction from non-regional sources. We developed an alternative decision-tree
      framework for HIV epidemic appraisals, based on a qualitative understanding of
      epidemiologic drivers, and demonstrated its applicability in India. The
      alternative framework offered a logical algorithm to characterize epidemics; it
      required minimal but key data. CONCLUSIONS: Traditional appraisals that utilize
      the distribution of prevalent and incident HIV infections in the short-term could
      misguide prevention priorities and potentially impede efforts to halt the
      trajectory of the HIV epidemic. An approach that characterizes local transmission
      dynamics provides a potentially more effective tool with which policy makers can
      design intervention programmes.

PMID- 22396757
TI  - Causes and correlates of calf mortality in captive Asian elephants (Elephas
      maximus).
AB  - Juvenile mortality is a key factor influencing population growth rate in density
      independent, predation-free, well-managed captive populations. Currently at least
      a quarter of all Asian elephants live in captivity, but both the wild and captive
      populations are unsustainable with the present fertility and calf mortality
      rates. Despite the need for detailed data on calf mortality to manage effectively
      populations and to minimize the need for capture from the wild, very little is
      known of the causes and correlates of calf mortality in Asian elephants. Here we
      use the world's largest multigenerational demographic dataset on a semi-captive
      population of Asian elephants compiled from timber camps in Myanmar to
      investigate the survival of calves (n = 1020) to age five born to captive-born
      mothers (n = 391) between 1960 and 1999. Mortality risk varied significantly
      across different ages and was higher for males at any age. Maternal reproductive
      history was associated with large differences in both stillbirth and liveborn
      mortality risk: first-time mothers had a higher risk of calf loss as did mothers
      producing another calf soon (<3.7 years) after a previous birth, and when giving
      birth at older age. Stillbirth (4%) and pre-weaning mortality (25.6%) were
      considerably lower than those reported for zoo elephants and used in published
      population viability analyses. A large proportion of deaths were caused by
      accidents and lack of maternal milk/calf weakness which both might be partly
      preventable by supplementary feeding of mothers and calves and work reduction of
      high-risk mothers. Our results on Myanmar timber elephants with an extensive
      keeping system provide an important comparison to compromised survivorship
      reported in zoo elephants. They have implications for improving captive working
      elephant management systems in range countries and for refining population
      viability analyses with realistic parameter values in order to predict future
      population size of the Asian elephant.

PMID- 22396758
TI  - Syndecans reside in sphingomyelin-enriched low-density fractions of the plasma
      membrane isolated from a parathyroid cell line.
AB  - BACKGROUND: Heparan sulfate proteoglycans (HSPGs) are one of the basic
      constituents of plasma membranes. Specific molecular interactions between HSPGs
      and a number of extracellular ligands have been reported. Mechanisms involved in
      controlling the localization and abundance of HSPG on specific domains on the
      cell surface, such as membrane rafts, could play important regulatory roles in
      signal transduction. METHODOLOGY/PRINCIPAL FINDINGS: Using metabolic
      radiolabeling and sucrose-density gradient ultracentrifugation techniques, we
      identified [(35)S]sulfate-labeled macromolecules associated with detergent
      resistant membranes (DRMs) isolated from a rat parathyroid cell line. DRM
      fractions showed high specific radioactivity ([(35)S]sulfate/mg protein),
      implying the specific recruitment of HSPGs to the membrane rafts. Identity of DRM
      associated [(35)S]sulfate-labeled molecules as HSPGs was confirmed by Western
      blotting with antibodies that recognize heparan sulfate (HS)-derived epitope.
      Analyses of core proteins by SDS-PAGE revealed bands with an apparent MW of
      syndecan-4 (30-33 kDa) and syndecan-1 (70 kDa) suggesting the presence of rafts
      with various HSPG species. DRM fractions enriched with HSPGs were characterized
      by high sphingomyelin content and found to only partially overlap with the
      fractions enriched in ganglioside GM1. HSPGs could be also detected in DRMs even
      after prior treatment of cells with heparitinase. CONCLUSIONS/SIGNIFICANCE: Both
      syndecan-1 and syndecan-4 have been found to specifically associate with membrane
      rafts and their association seemed independent of intact HS chains. Membrane
      rafts in which HSPGs reside were also enriched with sphingomyelin, suggesting
      their possible involvement in FGF signaling. Further studies, involving proteomic
      characterization of membrane domains containing HSPGs might improve our knowledge
      on the nature of HSPG-ligand interactions and their role in different signaling
      platforms.

PMID- 22396759
TI  - Automatic analysis of composite physical signals using non-negative factorization
      and information criterion.
AB  - In time-resolved spectroscopy, composite signal sequences representing energy
      transfer in fluorescence materials are measured, and the physical characteristics
      of the materials are analyzed. Each signal sequence is represented by a sum of
      non-negative signal components, which are expressed by model functions. For
      analyzing the physical characteristics of a measured signal sequence, the
      parameters of the model functions are estimated. Furthermore, in order to
      quantitatively analyze real measurement data and to reduce the risk of improper
      decisions, it is necessary to obtain the statistical characteristics from several
      sequences rather than just a single sequence. In the present paper, we propose an
      automatic method by which to analyze composite signals using non-negative
      factorization and an information criterion. The proposed method decomposes the
      composite signal sequences using non-negative factorization subjected to
      parametric base functions. The number of components (i.e., rank) is also
      estimated using Akaike's information criterion. Experiments using simulated and
      real data reveal that the proposed method automatically estimates the acceptable
      ranks and parameters.

PMID- 22396761
TI  - First molecular evidence for underestimated biodiversity of Rhachotropis
      (Crustacea, Amphipoda), with description of a new species.
AB  - The crustacean genus Rhachotropis has a worldwide distribution and amongst the
      largest bathymetric range known from any amphipod genus. DNA barcoding of new
      material from around New Zealand and the Ross Sea indicated depth-related
      biogeographic patterns. New Zealand Rhachotropis do not form a monophyletic
      clade. Species from bathyal depths on the Chatham Rise, east of New Zealand, show
      lower sequence divergence to bathyal species from California and the Arctic than
      to abyssal New Zealand species. Species sampled in the Kermadec Trench, north of
      New Zealand below 5000 m, seem to be more closely related to Ross Sea abyssal
      species than to the New Zealand shelf species. The worldwide geographic and
      bathymetric distribution for all Rhachotropis species is presented here. Depth
      may have a greater influence on phylogeny than geographic distance.Molecular and
      morphological investigations of Rhachotropis specimens from the Chatham Rise, New
      Zealand revealed a species new to science which is described in detail, including
      scanning electron microscopy. This increases the number of described species of
      Rhachotropis to 60 worldwide.

PMID- 22396760
TI  - SP7 inhibits osteoblast differentiation at a late stage in mice.
AB  - RUNX2 and SP7 are essential transcription factors for osteoblast differentiation
      at an early stage. Although RUNX2 inhibits osteoblast differentiation at a late
      stage, the function of SP7 at the late stage of osteoblast differentiation is not
      fully elucidated. Thus, we pursued the function of SP7 in osteoblast
      differentiation. RUNX2 induced Sp7 expression in Runx2(-/-) calvarial cells.
      Adenoviral transfer of sh-Sp7 into primary osteoblasts reduced the expression of
      Alpl, Col1a1, and Bglap2 and mineralization, whereas that of Sp7 reduced Bglap2
      expression and mineralization at a late stage of osteoblast differentiation. Sp7
      transgenic mice under the control of 2.3 kb Col1a1 promoter showed osteopenia and
      woven-bone like structure in the cortical bone, which was thin and less
      mineralized, in a dose-dependent manner. Further, the number of processes in the
      osteoblasts and osteocytes was reduced. Although the osteoblast density was
      increased, the bone formation was reduced. The frequency of BrdU incorporation
      was increased in the osteoblastic cells, while the expression of Col1a1, Spp1,
      Ibsp, and Bglap2 was reduced. Further, the osteopenia in Sp7 or Runx2 transgenic
      mice was worsened in Sp7/Runx2 double transgenic mice and the expression of
      Col1a1 and Bglap2 was reduced. The expression of Sp7 and Runx2 was not increased
      in Runx2 and Sp7 transgenic mice, respectively. The expression of endogenous Sp7
      was increased in Sp7 transgenic mice and Sp7-transduced cells; the introduction
      of Sp7 activated and sh-Sp7 inhibited Sp7 promoter; and ChIP assay showed the
      binding of endogenous SP7 in the proximal region of Sp7 promoter. These findings
      suggest that SP7 and RUNX2 inhibit osteoblast differentiation at a late stage in
      a manner independent of RUNX2 and SP7, respectively, and SP7 positively regulates
      its own promoter.

PMID- 22396762
TI  - Accurate detection of carcinoma cells by use of a cell microarray chip.
AB  - BACKGROUND: Accurate detection and analysis of circulating tumor cells plays an
      important role in the diagnosis and treatment of metastatic cancer treatment.
      METHODS AND FINDINGS: A cell microarray chip was used to detect spiked carcinoma
      cells among leukocytes. The chip, with 20,944 microchambers (105 um width and 50
      um depth), was made from polystyrene; and the formation of monolayers of
      leukocytes in the microchambers was observed. Cultured human T lymphoblastoid
      leukemia (CCRF-CEM) cells were used to examine the potential of the cell
      microarray chip for the detection of spiked carcinoma cells. A T lymphoblastoid
      leukemia suspension was dispersed on the chip surface, followed by 15 min
      standing to allow the leukocytes to settle down into the microchambers.
      Approximately 29 leukocytes were found in each microchamber when about 600,000
      leukocytes in total were dispersed onto a cell microarray chip. Similarly, when
      leukocytes isolated from human whole blood were used, approximately 89 leukocytes
      entered each microchamber when about 1,800,000 leukocytes in total were placed
      onto the cell microarray chip. After washing the chip surface, PE-labeled anti
      cytokeratin monoclonal antibody and APC-labeled anti-CD326 (EpCAM) monoclonal
      antibody solution were dispersed onto the chip surface and allowed to react for
      15 min; and then a microarray scanner was employed to detect any fluorescence
      positive cells within 20 min. In the experiments using spiked carcinoma cells
      (NCI-H1650, 0.01 to 0.0001%), accurate detection of carcinoma cells was achieved
      with PE-labeled anti-cytokeratin monoclonal antibody. Furthermore, verification
      of carcinoma cells in the microchambers was performed by double staining with the
      above monoclonal antibodies. CONCLUSION: The potential application of the cell
      microarray chip for the detection of CTCs was shown, thus demonstrating accurate
      detection by double staining for cytokeratin and EpCAM at the single carcinoma
      cell level.

PMID- 22396763
TI  - Function-based discovery of significant transcriptional temporal patterns in
      insulin stimulated muscle cells.
AB  - BACKGROUND: Insulin action on protein synthesis (translation of transcripts) and
      post-translational modifications, especially of those involving the reversible
      modifications such as phosphorylation of various signaling proteins, are
      extensively studied but insulin effect on transcription of genes, especially of
      transcriptional temporal patterns remains to be fully defined.
      METHODOLOGY/PRINCIPAL FINDINGS: To identify significant transcriptional temporal
      patterns we utilized primary differentiated rat skeletal muscle myotubes which
      were treated with insulin and samples were collected every 20 min for 8 hours.
      Pooled samples at every hour were analyzed by gene array approach to measure
      transcript levels. The patterns of transcript levels were analyzed based on a
      novel method that integrates selection, clustering, and functional annotation to
      find the main temporal patterns associated to functional groups of differentially
      expressed genes. 326 genes were found to be differentially expressed in response
      to in vitro insulin administration in skeletal muscle myotubes. Approximately 20%
      of the genes that were differentially expressed were identified as belonging to
      the insulin signaling pathway. Characteristic transcriptional temporal patterns
      include: (a) a slow and gradual decrease in gene expression, (b) a gradual
      increase in gene expression reaching a peak at about 5 hours and then reaching a
      plateau or an initial decrease and other different variable pattern of increase
      in gene expression over time. CONCLUSION/SIGNIFICANCE: The new method allows
      identifying characteristic dynamic responses to insulin stimulus, common to a
      number of genes and associated to the same functional group. The results
      demonstrate that insulin treatment elicited different clusters of gene transcript
      profile supporting a temporal regulation of gene expression by insulin in
      skeletal muscle cells.

PMID- 22396764
TI  - Post-translational regulation and trafficking of the granulin-containing protease
      RD21 of Arabidopsis thaliana.
AB  - RD21-like proteases are ubiquitous, plant-specific papain-like proteases typified
      by carrying a C-terminal granulin domain. RD21-like proteases are involved in
      immunity and associated with senescence and various types of biotic and abiotic
      stresses. Here, we interrogated Arabidopsis RD21 regulation and trafficking by
      site-directed mutagenesis, agroinfiltration, western blotting, protease activity
      profiling and protein degradation. Using an introduced N-glycan sensor,
      deglycosylation experiments and glyco-engineered N. benthamiana plants, we show
      that RD21 passes through the Golgi where it becomes fucosylated. Our studies
      demonstrate that RD21 is regulated at three post-translational levels. Prodomain
      removal is not blocked in the catalytic Cys mutant, indicating that RD21 is
      activated by a proteolytic cascade. However, RD21 activation in Arabidopsis does
      not require vacuolar processing enzymes (VPEs) or aleurain-like protease AALP. In
      contrast, granulin domain removal requires the catalytic Cys and His residues and
      is therefore autocatalytic. Furthermore, SDS can (re-)activate latent RD21 in
      Arabidopsis leaf extracts, indicating the existence of a third layer of post
      translational regulation, possibly mediated by endogenous inhibitors. RD21 causes
      a dominant protease activity in Arabidopsis leaf extracts, responsible for SDS
      induced proteome degradation.

PMID- 22396765
TI  - Endothelial neuropilin disruption in mice causes DiGeorge syndrome-like
      malformations via mechanisms distinct to those caused by loss of Tbx1.
AB  - The spectrum of human congenital malformations known as DiGeorge syndrome (DGS)
      is replicated in mice by mutation of Tbx1. Vegfa has been proposed as a modifier
      of DGS, based in part on the occurrence of comparable phenotypes in Tbx1 and
      Vegfa mutant mice. Many additional genes have been shown to cause DGS-like
      phenotypes in mice when mutated; these generally intersect in some manner with
      Tbx1, and therefore impact the same developmental processes in which Tbx1 itself
      is involved. In this study, using Tie2Cre, we show that endothelial-specific
      mutation of the gene encoding the VEGFA coreceptor neuropilin-1 (Nrp1) also
      replicates the most prominent terminal phenotypes that typify DGS. However, the
      developmental etiologies of these defects are fundamentally different from those
      caused by absence of TBX1. In Tie2Cre/Nrp1 mutants, initial pharyngeal
      organization is normal but subsequent pharyngeal organ growth is impaired, second
      heart field differentiation is normal but cardiac outflow tract cushion
      organization is distorted, neural crest cell migration is normal, and palatal
      mesenchyme proliferation is impaired with no change in apoptosis. Our results
      demonstrate that impairment of VEGF-dependent endothelial pathways leads to a
      spectrum of DiGeorge syndrome-type malformations, through processes that are
      distinguishable from those controlled by Tbx1.

PMID- 22396766
TI  - Retinoic acid-dependent signaling pathways and lineage events in the developing
      mouse spinal cord.
AB  - Studies in avian models have demonstrated an involvement of retinoid signaling in
      early neural tube patterning. The roles of this signaling pathway at later stages
      of spinal cord development are only partly characterized. Here we use Raldh2-null
      mouse mutants rescued from early embryonic lethality to study the consequences of
      lack of endogenous retinoic acid (RA) in the differentiating spinal cord. Mid
      gestation RA deficiency produces prominent structural and molecular deficiencies
      in dorsal regions of the spinal cord. While targets of Wnt signaling in the
      dorsal neuronal lineage are unaltered, reductions in Fibroblast Growth Factor
      (FGF) and Notch signaling are clearly observed. We further provide evidence that
      endogenous RA is capable of driving stem cell differentiation. Raldh2 deficiency
      results in a decreased number of spinal cord derived neurospheres, which exhibit
      a reduced differentiation potential. Raldh2-null neurospheres have a decreased
      number of cells expressing the neuronal marker beta-III-tubulin, while the nestin
      positive cell population is increased. Hence, in vivo retinoid deficiency
      impaired neural stem cell growth. We propose that RA has separable functions in
      the developing spinal cord to (i) maintain high levels of FGF and Notch signaling
      and (ii) drive stem cell differentiation, thus restricting both the numbers and
      the pluripotent character of neural stem cells.

PMID- 22396767
TI  - The contrasting relationships between betaine and homocysteine in two clinical
      cohorts are associated with plasma lipids and drug treatments.
AB  - BACKGROUND: Urinary betaine excretion positively correlated with plasma
      homocysteine in outpatients attending a lipid disorders clinic (lipid clinic
      study). We aimed to confirm this in subjects with established vascular disease.
      METHODS: The correlation between betaine excretion and homocysteine was compared
      in samples collected from subjects 4 months after hospitalization for an acute
      coronary episode (ACS study, 415 urine samples) and from 158 sequential patients
      visiting a lipid disorders clinic. PRINCIPAL FINDINGS: In contrast to the lipid
      clinic study, betaine excretion and plasma homocysteine did not correlate in the
      total ACS cohort. Differences between the patient groups included age, non-HDL
      cholesterol and medication. In ACS subjects with below median betaine excretion,
      excretion correlated (using log transformed data) negatively with plasma
      homocysteine (r = -0.17, p = 0.019, n = 199), with no correlation in the
      corresponding subset of the lipid clinic subjects. In ACS subjects with above
      median betaine excretion a positive trend (r = +0.10) between betaine excretion
      and homocysteine was not significant; the corresponding correlation in lipid
      clinic subjects was r = +0.42 (p = 0.0001). In ACS subjects, correlations were
      stronger when plasma non-HDL cholesterol and betaine excretion were above the
      median, r = +0.20 (p = 0.045); in subjects above median non-HDL cholesterol and
      below median betaine excretion, r = -0.26 (p = 0.012). ACS subjects taking
      diuretics or proton pump inhibitors had stronger correlations, negative with
      lower betaine excretion and positive with higher betaine excretion. CONCLUSIONS:
      Betaine excretion correlates with homocysteine in subjects with elevated blood
      lipids.

PMID- 22396768
TI  - Device thrombogenicity emulation: a novel method for optimizing mechanical
      circulatory support device thromboresistance.
AB  - Mechanical circulatory support (MCS) devices provide both short and long term
      hemodynamic support for advanced heart failure patients. Unfortunately these
      devices remain plagued by thromboembolic complications associated with chronic
      platelet activation--mandating complex, lifelong anticoagulation therapy. To
      address the unmet need for enhancing the thromboresistance of these devices to
      extend their long term use, we developed a universal predictive methodology
      entitled Device Thrombogenicity Emulation (DTE) that facilitates optimizing the
      thrombogenic performance of any MCS device--ideally to a level that may obviate
      the need for mandatory anticoagulation. DTE combines in silico numerical
      simulations with in vitro measurements by correlating device hemodynamics with
      platelet activity coagulation markers--before and after iterative design
      modifications aimed at achieving optimized thrombogenic performance. DTE proof-of
      concept is demonstrated by comparing two rotary Left Ventricular Assist Devices
      (LVADs) (DeBakey vs HeartAssist 5, Micromed Houston, TX), the latter a version of
      the former following optimization of geometrical features implicated in device
      thrombogenicity. Cumulative stresses that may drive platelets beyond their
      activation threshold were calculated along multiple flow trajectories and
      collapsed into probability density functions (PDFs) representing the device
      'thrombogenic footprint', indicating significantly reduced thrombogenicity for
      the optimized design. Platelet activity measurements performed in the actual pump
      prototypes operating under clinical conditions in circulation flow loops--before
      and after the optimization with the DTE methodology, show an order of magnitude
      lower platelet activity rate for the optimized device. The robust capability of
      this predictive technology--demonstrated here for attaining safe and cost
      effective pre-clinical MCS thrombo-optimization--indicates its potential for
      reducing device thrombogenicity to a level that may significantly limit the
      extent of concomitant antithrombotic pharmacotherapy needed for safe clinical
      device use.

PMID- 22396769
TI  - First efficacy results of capecitabine with anthracycline- and taxane-based
      adjuvant therapy in high-risk early breast cancer: a meta-analysis.
AB  - BACKGROUND: Capecitabine is effective and indicated for the salvage treatment of
      metastatic breast cancer. Therefore, it is essential to evaluate the efficacy of
      capecitabine in the adjuvant setting. There have been two large randomized
      studies to determine whether patients with high-risk early breast cancer benefit
      from the addition of capecitabine to standard chemotherapy, but they have yielded
      inconsistent results. We first undertook a meta-analysis to evaluate the efficacy
      of the addition of capecitabine over standard treatment. METHODS: PubMed, EBSCO,
      Web of Science, conference proceedings and key trials were searched from 1998 to
      2011. The hazard ratio (HR) was used to evaluate the efficacy of a taxane
      anthracycline regimen and a taxane-anthracycline-capecitabine regimen in early
      breast cancer. All of the data from each study use either fixed-effects or random
      effects by Stata. FINDINGS: We found significant improvement in the additional
      capecitabine arm versus control in disease-free survival (DFS) (HR = 0.83, 95%
      CI: 0.71-0.98, P = 0.027), overall survival (OS) (HR = 0.71, 95% CI: 0.57-0.88, P
      = 0.002), distant recurrence (HR = 0.79, 95% CI: 0.66-0.94, P = 0.008) and the
      death from breast cancer only (HR = 0.65, 95% CI: 0.51-0.83, P = 0.001).
      Meanwhile, the subgroup analysis revealed that capecitabine improved the DFS in
      triple negative (HR = 0.71, 95% CI: 0.53-0.96, P = 0.028), hormone receptor
      negative (HR = 0.73, CI: 0.56-0.94, P = 0.017) and HER2 negative (HR = 0.81, CI:
      0.67-0.98, P = 0.034) patients. CONCLUSION: Due to the synergistic effect of
      taxane and capecitabine, taxane-anthracycline-capecitabine regimen may
      effectively improve the efficacy in the adjuvant setting and may be a novel
      generation of adjuvant chemotherapy regimen. The results of the current meta
      analysis support this hypothesis and indicate that taxane-based regimen with
      capecitabine may be an effective, convenient, and well tolerated regimen in
      patients with early breast cancer.

PMID- 22396771
TI  - Population based study of 12 autoimmune diseases in Sardinia, Italy: prevalence
      and comorbidity.
AB  - BACKGROUND: The limited availability of prevalence data based on a representative
      sample of the general population, and the limited number of diseases considered
      in studies about co-morbidity are the critical factors in study of autoimmune
      diseases. This paper describes the prevalence of 12 autoimmune diseases in a
      representative sample of the general population in the South of Sardinia, Italy,
      and tests the hypothesis of an overall association among these diseases. METHODS:
      Data were obtained from 21 GPs. The sample included 25,885 people. Prevalence
      data were expressed with 95% Poisson C.I. The hypothesis of an overall
      association between autoimmune diseases was tested by evaluating the co
      occurrence within individuals. RESULTS: Prevalence per 100,000 are: 552
      rheumatoid arthritis, 124 ulcerative colitis, 15 Crohn's disease, 464 type 1
      diabetes, 81 systemic lupus erythematosus, 124 celiac disease, 35 myasthenia
      gravis, 939 psoriasis/psoriatic arthritis, 35 systemic sclerosis, 224 multiple
      sclerosis, 31 Sjogren's syndrome, and 2,619 autoimmune thyroiditis. An overall
      association between autoimmune disorders was highlighted. CONCLUSIONS: The
      comparisons with prevalence reported in current literature do not show outlier
      values, except possibly for a few diseases like celiac disease and myasthenia
      gravis. People already affected by a first autoimmune disease have a higher
      probability of being affected by a second autoimmune disorder. In the present
      study, the sample size, together with the low overall prevalence of autoimmune
      diseases in the population, did not allow us to examine which diseases are most
      frequently associated with other autoimmune diseases. However, this paper makes
      available an adequate control population for future clinical studies aimed at
      exploring the co-morbidity of specific pairs of autoimmune diseases.

PMID- 22396770
TI  - Kainate receptor-mediated modulation of hippocampal fast spiking interneurons in
      a rat model of schizophrenia.
AB  - Kainate receptor (KAR) subunits are believed to be involved in abnormal GABAergic
      neurotransmission in the hippocampus (HIPP) in schizophrenia (SZ) and bipolar
      disorder. Postmortem studies have shown changes in the expression of the GluR5/6
      subunits of KARs in the stratum oriens (SO) of sectors CA2/3, where the
      basolateral amygdala (BLA) sends a robust projection. Previous work using a rat
      model of SZ demonstrated that BLA activation leads to electrophysiological
      changes in fast-spiking interneurons in SO of CA2/3. The present study explores
      KAR modulation of interneurons in CA2/3 in response to BLA activation. Intrinsic
      firing properties of these interneurons through KAR-mediated activity were
      measured with patch-clamp recordings from rats that received 15 days of
      picrotoxin infusion into the BLA. Chronic BLA activation induced changes in the
      firing properties of CA2/3 interneurons associated with modifications in the
      function of KARs. Specifically, the responsiveness of these interneurons to
      activation of KARs was diminished in picrotoxin-treated rats, while the after
      hyperpolarization (AHP) amplitude was increased. In addition, we tested blockers
      of KAR subunits which have been shown to have altered gene expression in SO
      sector CA2/3 of SZ subjects. The GluR5 antagonist UBP296 further decreased AP
      frequency and increased AHP amplitude in picrotoxin-treated rats. Application of
      the GluR6/7 antagonist NS102 suggested that activation of GluR6/7 KARs may be
      required to maintain the high firing rates in SO interneurons in the presence of
      KA. Moreover, the GluR6/7 KAR-mediated signaling may be suppressed in PICRO
      treated rats. Our findings indicate that glutamatergic activity from the BLA may
      modulate the firing properties of CA2/3 interneurons through GluR5 and GluR6/7
      KARs. These receptors are expressed in GABAergic interneurons and play a key role
      in the synchronization of gamma oscillations. Modulation of interneuronal
      activity through KARs in response to amygdala activation may lead to abnormal
      oscillatory rhythms reported in SZ subjects.

PMID- 22396772
TI  - Immunological and molecular correlates of disease recurrence after liver
      resection for hepatocellular carcinoma.
AB  - The definition of the risk of hepatocellular carcinoma (HCC) recurrence after
      resection represents a central issue to improve the clinical management of
      patients. In this study we examined the prognostic relevance of infiltrating
      immune cell subsets in the tumor (TIL) and in nontumorous (NT) liver (LIL), and
      the expression of immune-related and lineage-specific mRNAs in HCC and NT liver
      derived from 42 patients. The phenotype of infiltrating cells was analyzed by
      flow cytometry, and mRNA expression in liver tissue was examined by real-time
      reverse transcription (RT)-PCR. The tumor immune microenvironment was enriched in
      inhibitory and dysfunctional cell subsets. Enrichment in CD4+ T-cells and in
      particular CD4 and CD8+ memory subsets within TIL was predictive of better
      overall survival (OS) and time to recurrence (TTR). Increased programmed death
      ligand 1 (PDL1) mRNA content and higher prevalence of invariant NKT (iNKT) cells
      were associated with shorter OS and TTR, respectively. By combined evaluation of
      infiltrating cell subsets along with mRNA profiling of immune and tumor related
      genes, we identified the intratumoral frequency of memory T-cells and iNKT-cells
      as well as PDL1 expression as the best predictors of clinical outcome. HCC
      infiltrate is characterized by the expression of molecules with negative
      regulatory function that may favor tumor recurrence and poor survival.

PMID- 22396774
TI  - Self-assemblage and quorum in the earthworm Eisenia fetida (Oligochaete,
      Lumbricidae).
AB  - Despite their ubiquity and ecological significance in temperate ecosystems, the
      behavioural ecology of earthworms is not well described. This study examines the
      mechanisms that govern aggregation behaviour specially the tendency of
      individuals to leave or join groups in the compost earthworm Eisenia fetida, a
      species with considerable economic importance, especially in waste management
      applications. Through behavioural assays combined with mathematical modelling, we
      provide the first evidence of self-assembled social structures in earthworms and
      describe key mechanisms involved in cluster formation. We found that the
      probability of an individual joining a group increased with group size, while the
      probability of leaving decreased. Moreover, attraction to groups located at a
      distance was observed, suggesting a role for volatile cues in cluster formation.
      The size of earthworm clusters appears to be a key factor determining the
      stability of the group. These findings enhance our understanding of intra
      specific interactions in earthworms and have potential implications for
      extraction and collection of earthworms in vermicomposting processes.

PMID- 22396773
TI  - Chemotherapeutics and radiation stimulate MHC class I expression through elevated
      interferon-beta signaling in breast cancer cells.
AB  - Low doses of anticancer drugs have been shown to enhance antitumor immune
      response and increase the efficacy of immunotherapy. The molecular basis for such
      effects remains elusive, although selective depletion of T regulatory cells has
      been demonstrated. In the current studies, we demonstrate that topotecan (TPT), a
      topoisomerase I-targeting drug with a well-defined mechanism of action,
      stimulates major histocompatibility complex class I (MHC I) expression in breast
      cancer cells through elevated expression/secretion of interferon-beta (IFN-beta)
      and activation of type I IFN signaling. First, we show that TPT treatment
      elevates the expression of both total and cell-surface MHC I in breast cancer
      cells. Second, conditioned media from TPT-treated breast cancer ZR-75-1 cells
      induce elevated expression of cell-surface MHC I in drug-naive recipient cells,
      suggesting the involvement of cytokines and/or other secreted molecules.
      Consistently, TPT-treated cells exhibit elevated expression of multiple cytokines
      such as IFN-beta, TNF-alpha, IL-6 and IL-8. Third, either knocking down the type
      I interferon receptor subunit 1 (IFNAR1) or addition of neutralizing antibody
      against IFN-beta results in reduced MHC I expression in TPT-treated cells.
      Together, these results suggest that TPT induces increased IFN-beta
      autocrine/paracrine signaling through type I IFN receptor, resulting in the
      elevated MHC I expression in tumor cells. Studies have also demonstrated that
      other chemotherapeutic agents (e.g. etoposide, cisplatin, paclitaxel and
      vinblastine) similarly induce increased IFN-beta secretion and elevated MHC I
      expression. In addition, conditioned media from gamma-irradiated donor cells are
      shown to induce IFN-beta-dependent MHC I expression in unirradiated recipient
      cells. In the aggregate, our results suggest that many cancer therapeutics induce
      elevated tumor antigen presentation through MHC I, which could represent a common
      mechanism for enhanced antitumor immune response through T cell cytotoxicity
      during metronomic chemotherapy, as well as increased efficacy of combined chemo-
      (or radio-)/immuno-therapy.

PMID- 22396775
TI  - Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial
      cells as a blood-brain barrier model.
AB  - BACKGROUND: The blood-brain barrier (BBB) represents an insurmountable obstacle
      for most drugs thus obstructing an effective treatment of many brain diseases.
      One solution for overcoming this barrier is a transport by binding of these drugs
      to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to
      play a major role in the nanoparticle-mediated drug transport across the BBB.
      However, at present the underlying mechanism is incompletely understood.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, the uptake of the ApoE-modified
      nanoparticles into the brain capillary endothelial cells was investigated to
      differentiate between active and passive uptake mechanism by flow cytometry and
      confocal laser scanning microscopy. Furthermore, different in vitro co-incubation
      experiments were performed with competing ligands of the respective receptor.
      CONCLUSIONS/SIGNIFICANCE: This study confirms an active endocytotic uptake
      mechanism and shows the involvement of low density lipoprotein receptor family
      members, notably the low density lipoprotein receptor related protein, on the
      uptake of the ApoE-modified nanoparticles into the brain capillary endothelial
      cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles
      enables future developments to rationally create very specific and effective
      carriers to overcome the blood-brain barrier.

PMID- 22396776
TI  - Wire marking results in a small but significant reduction in avian mortality at
      power lines: a BACI designed study.
AB  - BACKGROUND: Collision with electric power lines is a conservation problem for
      many bird species. Although the implementation of flight diverters is rapidly
      increasing, few well-designed studies supporting the effectiveness of this costly
      conservation measure have been published. METHODOLOGY/PRINCIPAL FINDINGS: We
      provide information on the largest worldwide marking experiment to date,
      including carcass searches at 35 (15 experimental, 20 control) power lines
      totalling 72.5 km, at both transmission (220 kV) and distribution (15 kV-45 kV)
      lines. We found carcasses of 45 species, 19 of conservation concern. Numbers of
      carcasses found were corrected to account for carcass losses due to removal by
      scavengers or being overlooked by researchers, resulting in an estimated
      collision rate of 8.2 collisions per km per month. We observed a small (9.6%) but
      significant decrease in the number of casualties after line marking compared to
      before line marking in experimental lines. This was not observed in control
      lines. We found no influence of either marker size (large vs. small spirals,
      sample of distribution lines only) or power line type (transmission vs.
      distribution, sample of large spirals only) on the collision rate when we
      analyzed all species together. However, great bustard mortality was slightly
      lower when lines were marked with large spirals and in transmission lines after
      marking. CONCLUSIONS: Our results confirm the overall effectiveness of wire
      marking as a way to reduce, but not eliminate, bird collisions with power lines.
      If raw field data are not corrected by carcass losses due to scavengers and
      missed observations, findings may be biased. The high cost of this conservation
      measure suggests a need for more studies to improve its application, including
      wire marking with non-visual devices. Our findings suggest that different species
      may respond differently to marking, implying that species-specific patterns
      should be explored, at least for species of conservation concern.

PMID- 22396777
TI  - M3 subtype of muscarinic acetylcholine receptor promotes cardioprotection via the
      suppression of miR-376b-5p.
AB  - The M(3) subtype of muscarinic acetylcholine receptors (M(3)-mAChR) plays a
      protective role in myocardial ischemia and microRNAs (miRNAs) participate in many
      cardiac pathophysiological processes, including ischemia-induced cardiac injury.
      However, the role of miRNAs in M(3)-mAChR mediated cardioprotection remains
      unexplored. The present study was designed to identify miRNAs that are involved
      in cardioprotective effects of M(3)-mAChR against myocardial ischemia and
      elucidate the underlying mechanisms. We established rat model of myocardial
      ischemia and performed miRNA microarray analysis to identify miRNAs involved in
      the cardioprotection of M(3)-mAChR. In H9c2 cells, the viability, intracellular
      free Ca(2+) concentration ([Ca(2+)]i), intracellular reactive oxygen species
      (ROS), miR-376b-5p expression level, brain derived neurophic factor (BDNF) and
      nuclear factor kappa-B (NF-kappaB) levels were measured. Our results demonstrated
      that M(3)-mAChR protected myocardial ischemia injury. Microarray analysis and qRT
      PCR revealed that miR-376b-5p was significantly up-regulated in ischemic heart
      tissue and the M(3)-mAChRs agonist choline reversed its up-regulation. In vitro,
      miR-376b-5p promoted H(2)O(2)-induced H9c2 cell injuries measured by cells
      viability, [Ca(2+)]i and ROS. Western blot and luciferase assay identified BDNF
      as a direct target of miR-376b-5p. M(3)-mAChR activated NF-kappaB and thereby
      inhibited miR-376b-5p expression. Our data show that a novel M(3)-mAChR/NF
      kappaB/miR-376b-5p/BDNF axis plays an important role in modulating
      cardioprotection. MiR-376b-5p promotes myocardial ischemia injury possibly by
      inhibiting BDNF expression and M(3)-mAChR provides cardioprotection at least
      partially mediated by the downregulation of miR-376b-5p through NF-kappaB. These
      findings provide new insight into the potential mechanism by which M(3)-mAChR
      provides cardioprotection against myocardial ischemia injury.

PMID- 22396778
TI  - Effects of S-propargyl-cysteine (SPRC) in caerulein-induced acute pancreatitis in
      mice.
AB  - Hydrogen sulfide (H(2)S), a novel gaseous messenger, is synthesized endogenously
      from L-cysteine by two pyridoxal-5'-phosphate-dependent enzymes, cystathionine
      beta-synthase (CBS) and cystathionine gamma-lyase (CSE). S-propargyl-cysteine
      (SPRC) is a slow H(2)S releasing drug that provides cysteine, a substrate of CSE.
      The present study was aimed to investigate the effects of SPRC in an in vivo
      model of acute pancreatitis (AP) in mice. AP was induced in mice by hourly
      caerulein injections (50 ug/kg) for 10 hours. Mice were treated with SPRC (10
      mg/kg) or vehicle (distilled water). SPRC was administered either 12 h before or
      3 h before the induction of pancreatitis. Mice were sacrificed 1 h after the last
      caerulein injection. Blood, pancreas and lung tissues were collected and
      processed to measure the plasma amylase, plasma H(2)S, myeloperoxidase (MPO)
      activities and cytokine levels in pancreas and lung. The results revealed that
      significant reduction of inflammation, both in pancreas and lung was associated
      with SPRC given 3 h prior to the induction of AP. Furthermore, the beneficial
      effects of SPRC were associated with reduction of pancreatic and pulmonary pro
      inflammatory cytokines and increase of anti-inflammatory cytokine. SPRC
      administered 12 h before AP induction did not cause significant improvement in
      pancreatic and lung inflammation. Plasma H(2)S concentration showed significant
      difference in H(2)S levels between control, vehicle and SPRC (administered 3 h
      before AP) treatment groups. In conclusion, these data provide evidence for
      protective effects of SPRC in AP possibly by virtue of its slow release of
      endogenous H(2)S.

PMID- 22396779
TI  - Bead array direct rRNA capture assay (rCapA) for amplification free speciation of
      Mycobacterium cultures.
AB  - Mycobacterium cultures, from patients suspected of tuberculosis or nontuberculous
      mycobacteria (NTM) infection, need to be identified. It is most critical to
      identify cultures belonging to the Mycobacterium tuberculosis complex, but also
      important to recognize clinically irrelevant or important NTM to allow
      appropriate patient management. Identification of M. tuberculosis can be achieved
      by a simple and cheap lateral flow assay, but identification of other
      Mycobacterium spp. generally requires more complex molecular methods. Here we
      demonstrate that a paramagnetic liquid bead array method can be used to capture
      mycobacterial rRNA in crude lysates of positive cultures and use a robust reader
      to identify the species in a direct and sensitive manner. We developed an array
      composed of paramagnetic beads coupled to oligonucleotides to capture 16 rRNA
      from eight specific Mycobacterium species and a single secondary biotinilated
      reporter probe to allow the captured rRNA to be detected. A ninth less specific
      bead and its associated reporter probe, designed to capture 23S rRNA from
      mycobacteria and related genera, is included as an internal control to confirm
      the presence of bacterial rRNA from a GC rich Gram variable genera. Using this
      rRNA capture assay (rCapA) with the array developed we were already able to
      confirm the presence of members of the M. tuberculosis complex and to
      discriminate a range of NTM species. This approach is not based on DNA
      amplification and therefore does not require precautions to avoid amplicon
      contamination. Moreover, the new generation of stable and cost effective liquid
      bead readers provides the necessary multiplexing potential to develop a robust
      and highly discriminatory assay.

PMID- 22396780
TI  - Dissociating markers of senescence and protective ability in memory T cells.
AB  - No unique transcription factor or biomarker has been identified to reliably
      distinguish effector from memory T cells. Instead a set of surface markers
      including IL-7Ralpha and KLRG1 is commonly used to predict the potential of CD8
      effector T cells to differentiate into memory cells. Similarly, these surface
      markers together with the tumor necrosis factor family member CD27 are frequently
      used to predict a memory T cell's ability to mount a recall response. Expression
      of these markers changes every time a memory cell is stimulated and repeated
      stimulation can lead to T cell senescence and loss of memory T cell
      responsiveness. This is a concern for prime-boost vaccine strategies which
      repeatedly stimulate T cells with the aim of increasing memory T cell frequency.
      The molecular cues that cause senescence are still unknown, but cell division
      history is likely to play a major role. We sought to dissect the roles of
      inflammation and cell division history in developing T cell senescence and their
      impact on the expression pattern of commonly used markers of senescence. We
      developed a system that allows priming of CD8 T cells with minimal inflammation
      and without acquisition of maximal effector function, such as granzyme
      expression, but a cell division history similar to priming with systemic
      inflammation. Memory cells derived from minimal effector T cells are fully
      functional upon rechallenge, have full access to non-lymphoid tissue and appear
      to be less senescent by phenotype upon rechallenge. However, we report here that
      these currently used biomarkers to measure senescence do not predict
      proliferative potential or protective ability, but merely reflect initial priming
      conditions.

PMID- 22396781
TI  - Meta-analysis of two genome-wide association studies of bovine paratuberculosis.
AB  - BACKGROUND: Bovine paratuberculosis (ParaTB) also known as Johne's disease, is a
      contagious fatal disease resulting from infection by Mycobacterium avium
      subspecies paratuberculosis (MAP). Previous studies have identified loci
      associated with ParaTB using different measurements to define cases and controls.
      The objective of this study was to combine the data from two recent studies to
      identify genetic loci associated with MAP tissue infection and humoral immune
      response, defined by MAP ELISA-positive cattle, by comparing cases and control
      animals for one or both measures of infection. METHODOLOGY/PRINCIPAL FINDINGS:
      The two populations used for the association analyses were a cohort of MAP tissue
      infected animals and control Holstein cows from the USA and the second cohort
      composed of ELISA-positive and ELISA-negative Holstein cows from Italy.
      Altogether 1190 cattle were genotyped with the Illumina BovineSNP50 BeadChip. SNP
      markers were removed if the minor allele frequency <0.01 or genotyping failure
      was >5%. Animals were removed with >5% genotyping failure. Whole genome
      association analyses were conducted with the GRAMMAR-CG method using two
      different definitions of control populations. CONCLUSION/SIGNIFICANCE: The
      analyses identified several loci (P<5 e-05) associated with ParaTB, defined by
      positive ELISA and presence of bacteria in tissue compared to ELISA and tissue
      negative animals, on chromosomes 1, 12 and 15 and one unassigned SNP. These
      results confirmed associations on chromosome 12 and the unassigned SNP with
      ParaTB which had been found in the Italian population alone. Furthermore, several
      additional genomic regions were found associated with ParaTB when ELISA and
      tissue positive animals were compared with tissue negative samples. These loci
      were on chromosomes 1, 6, 7, 13, 16, 21,23 and 25 (P<5 e-05). The results clearly
      indicate the importance of the phenotype definition when seeking to identify
      markers associated with different disease responses.

PMID- 22396782
TI  - Do stacked species distribution models reflect altitudinal diversity patterns?
AB  - The objective of this study was to evaluate the performance of stacked species
      distribution models in predicting the alpha and gamma species diversity patterns
      of two important plant clades along elevation in the Andes. We modelled the
      distribution of the species in the Anthurium genus (53 species) and the
      Bromeliaceae family (89 species) using six modelling techniques. We combined all
      of the predictions for the same species in ensemble models based on two different
      criteria: the average of the rescaled predictions by all techniques and the
      average of the best techniques. The rescaled predictions were then reclassified
      into binary predictions (presence/absence). By stacking either the original
      predictions or binary predictions for both ensemble procedures, we obtained four
      different species richness models per taxa. The gamma and alpha diversity per
      elevation band (500 m) was also computed. To evaluate the prediction abilities
      for the four predictions of species richness and gamma diversity, the models were
      compared with the real data along an elevation gradient that was independently
      compiled by specialists. Finally, we also tested whether our richness models
      performed better than a null model of altitudinal changes of diversity based on
      the literature. Stacking of the ensemble prediction of the individual species
      models generated richness models that proved to be well correlated with the
      observed alpha diversity richness patterns along elevation and with the gamma
      diversity derived from the literature. Overall, these models tend to overpredict
      species richness. The use of the ensemble predictions from the species models
      built with different techniques seems very promising for modelling of species
      assemblages. Stacking of the binary models reduced the over-prediction, although
      more research is needed. The randomisation test proved to be a promising method
      for testing the performance of the stacked models, but other implementations may
      still be developed.

PMID- 22396783
TI  - Interactive rhythmic auditory stimulation reinstates natural 1/f timing in gait
      of Parkinson's patients.
AB  - Parkinson's disease (PD) and basal ganglia dysfunction impair movement timing,
      which leads to gait instability and falls. Parkinsonian gait consists of random,
      disconnected stride times--rather than the 1/f structure observed in healthy gait
      -and this randomness of stride times (low fractal scaling) predicts falling.
      Walking with fixed-tempo Rhythmic Auditory Stimulation (RAS) can improve many
      aspects of gait timing; however, it lowers fractal scaling (away from healthy 1/f
      structure) and requires attention. Here we show that interactive rhythmic
      auditory stimulation reestablishes healthy gait dynamics in PD patients. In the
      experiment, PD patients and healthy participants walked with a) no auditory
      stimulation, b) fixed-tempo RAS, and c) interactive rhythmic auditory
      stimulation. The interactive system used foot sensors and nonlinear oscillators
      to track and mutually entrain with the human's step timing. Patients consistently
      synchronized with the interactive system, their fractal scaling returned to
      levels of healthy participants, and their gait felt more stable to them. Patients
      and healthy participants rarely synchronized with fixed-tempo RAS, and when they
      did synchronize their fractal scaling declined from healthy 1/f levels. Five
      minutes after removing the interactive rhythmic stimulation, the PD patients'
      gait retained high fractal scaling, suggesting that the interaction stabilized
      the internal rhythm generating system and reintegrated timing networks. The
      experiment demonstrates that complex interaction is important in the
      (re)emergence of 1/f structure in human behavior and that interactive rhythmic
      auditory stimulation is a promising therapeutic tool for improving gait of PD
      patients.

PMID- 22396784
TI  - EBV-encoded LMP1 upregulates Igkappa 3'enhancer activity and Igkappa expression
      in nasopharyngeal cancer cells by activating the Ets-1 through ERKs signaling.
AB  - Accumulating evidence indicates that epithelial cancer cells, including
      nasopharyngeal carcinoma (NPC) cells, express immunoglobulins (Igs). We
      previously found that the expression of the kappa light chain protein in NPC
      cells can be upregulated by the EBV-encoded latent membrane protein 1 (LMP1). In
      the present study, we used NPC cell lines as models and found that LMP1-augmented
      kappa production corresponds with elevations in ERKs phosphorylation. PD98059
      attenuates LMP1-induced ERKs phosphorylation resulting in decreased expression of
      the kappa light chain. ERK-specific small interfering RNA blunts LMP1-induced
      kappa light chain gene expression. Luciferase reporter assays demonstrate that
      immunoglobulin kappa 3' enhancer (3'E(kappa)) is active in Igkappa-expressing NPC
      cells and LMP1 upregulates the activity of 3'E(kappa) in NPC cells. Moreover,
      mutation analysis of the PU binding site in 3'E(kappa) and inhibition of the
      MEK/ERKs pathway by PD98059 indicate that the PU site is functional and LMP1
      enhanced 3'E(kappa) activity is partly regulated by this site. PD98059 treatment
      also leads to a concentration-dependent inhibition of LMP1-induced Ets-1
      expression and phosphorylation, which corresponds with a dose-dependent
      attenuation of LMP1-induced ERK phosphorylation and kappa light chain expression.
      Suppression of endogenous Ets-1 by small interfering RNA is accompanied by a
      decrease of Ig kappa light chain expression. Gel shift assays using nuclear
      extracts of NPC cells indicate that the transcription factor Ets-1 is recruited
      by LMP1 to the PU motif within 3'E(kappa)in vitro. ChIP assays further
      demonstrate Ets-1 binding to the PU motif of 3'E(kappa) in cells. These results
      suggest that LMP1 upregulates 3'E(kappa) activity and kappa gene expression by
      activating the Ets-1 transcription factor through the ERKs signaling pathway. Our
      studies provide evidence for a novel regulatory mechanism of kappa expression, by
      which virus-encoded proteins activate the kappa 3' enhancer through activating
      transcription factors in non-B epithelial cancer cells.

PMID- 22396785
TI  - Changes in channel trafficking and protein stability caused by LQT2 mutations in
      the PAS domain of the HERG channel.
AB  - Inherited human long-QT2 syndrome (LQTS) results from mutations in the gene
      encoding the HERG channel. Several LQT2-associated mutations have been mapped to
      the amino terminal cytoplasmic Per-Arnt-Sim (PAS) domain of the HERG1a channel
      subunit. Here we have characterized the trafficking properties of some LQT2
      associated PAS domain mutants and analyzed rescue of the trafficking mutants by
      low temperature (27 degrees C) or by the pore blocker drug E4031. We show that
      the LQT2-associated mutations in the PAS domain of the HERG channel display
      molecular properties that are distinct from the properties of LQT2-associated
      mutations in the trans-membrane region. Unlike the latter, many of the tested PAS
      domain LQT2-associated mutations do not result in trafficking deficiency of the
      channel. Moreover, the majority of the PAS domain mutations that cause
      trafficking deficiencies are not rescued by a pore blocking drug. We have also
      explored the in vitro folding stability properties of isolated mutant PAS domain
      proteins using a thermal unfolding fluorescence assay and a chemical unfolding
      assay.

PMID- 22396787
TI  - Modeling trap-awareness and related phenomena in capture-recapture studies.
AB  - Trap-awareness and related phenomena whereby successive capture events are not
      independent is a feature of the majority of capture-recapture studies. This
      phenomenon was up to now difficult to incorporate in open population models and
      most authors have chosen to neglect it although this may have damaging
      consequences. Focusing on the situation where animals exhibit a trap response at
      the occasion immediately following one where they have been trapped but revert to
      their original naive state if they are missed once, we show that trap-dependence
      is more naturally viewed as a state transition and is amenable to the current
      models of capture-recapture. This approach has the potential to accommodate
      lasting or progressively waning trap effects.

PMID- 22396786
TI  - CSF concentrations of cAMP and cGMP are lower in patients with Creutzfeldt-Jakob
      disease but not Parkinson's disease and amyotrophic lateral sclerosis.
AB  - BACKGROUND: The cyclic nucleotides cyclic adenosine-3',5'-monophosphate (cAMP)
      and cyclic guanosine-3',5'-monophosphate (cGMP) are important second messengers
      and are potential biomarkers for Parkinson's disease (PD), amyotrophic lateral
      sclerosis (ALS) and Creutzfeldt-Jakob disease (CJD). METHODOLOGY/PRINCIPAL
      FINDINGS: Here, we investigated by liquid chromatography/tandem mass spectrometry
      (LC-MS/MS) the cerebrospinal fluid (CSF) concentrations of cAMP and cGMP of 82
      patients and evaluated their diagnostic potency as biomarkers. For comparison
      with a well-accepted biomarker, we measured tau concentrations in CSF of CJD and
      control patients. CJD patients (n = 15) had lower cAMP (-70%) and cGMP (-55%)
      concentrations in CSF compared with controls (n = 11). There was no difference in
      PD, PD dementia (PDD) and ALS cases. Receiver operating characteristic (ROC)
      curve analyses confirmed cAMP and cGMP as valuable diagnostic markers for CJD
      indicated by the area under the curve (AUC) of 0.86 (cAMP) and 0.85 (cGMP). We
      calculated a sensitivity of 100% and specificity of 64% for cAMP and a
      sensitivity of 67% and specificity of 100% for cGMP. The combination of both
      nucleotides increased the sensitivity to 80% and specificity to 91% for the term
      cAMPxcGMP (AUC 0.92) and to 93% and 100% for the ratio tau/cAMP (AUC 0.99).
      CONCLUSIONS/SIGNIFICANCE: We conclude that the CSF determination of cAMP and cGMP
      may easily be included in the diagnosis of CJD and could be helpful in monitoring
      disease progression as well as in therapy control.

PMID- 22396788
TI  - Lymphocyte subpopulations in lymph nodes and peripheral blood: a comparison
      between patients with stable angina and acute coronary syndrome.
AB  - OBJECTIVE: Atherosclerosis is characterized by a chronic inflammatory response
      involving activated T cells and impairment of natural killer (NK) cells. An
      increased T cell activity has been associated with plaque instability and risk of
      acute cardiac events. Lymphocyte analyses in blood are widely used to evaluate
      the immune status. However, peripheral blood contains only a minor proportion of
      lymphocytes. In this study, we hypothesized that thoracic lymph nodes from
      patients with stable angina (SA) and acute coronary syndrome (ACS) might add
      information to peripheral blood analyses. METHODS: Peripheral blood and lymph
      nodes were collected during coronary by-pass surgery in 13 patients with SA and
      13 patients with ACS. Lymphocyte subpopulations were assessed by flow cytometry
      using antibodies against CD3, CD4, CD8, CD19, CD16/56, CD25, Foxp3, CD69, HLA-DR,
      IL-18 receptor (R) and CCR4. RESULTS: Lymph nodes revealed a lymphocyte
      subpopulation profile substantially differing from that in blood including a
      higher proportion of B cells, lower proportions of CD8(+) T cells and NK cells
      and a 2-fold higher CD4/CD8 ratio. CD4(+)CD69(+) cells as well as Foxp3(+)
      regulatory T cells were markedly enriched in lymph nodes (p<0.001) while T helper
      1-like (CD4(+)IL-18R+) cells were more frequent in blood (p<0.001). The only
      significant differences between ACS and SA patients involved NK cells that were
      reduced in the ACS group. However, despite being reduced, the NK cell fraction in
      ACS patients contained a significantly higher proportion of IL-18R(+) cells
      compared with SA patients (p<0.05). CONCLUSION: There were several differences in
      lymphocyte subpopulations between blood and lymph nodes. However, the lymphocyte
      perturbations in peripheral blood of ACS patients compared with SA patients were
      not mirrored in lymph nodes. The findings indicate that lymph node analyses in
      multivessel coronary artery disease may not reveal any major changes in the
      immune response that are not detectable in blood.

PMID- 22396789
TI  - Monodansylpentane as a blue-fluorescent lipid-droplet marker for multi-color live
      cell imaging.
AB  - Lipid droplets (LDs) are dynamic cellular organelles responsible for the storage
      of neutral lipids, and are associated with a multitude of metabolic syndromes.
      Here we report monodansylpentane (MDH) as a high contrast blue-fluorescent marker
      for LDs. The unique spectral properties make MDH easily combinable with other
      green and red fluorescent reporters for multicolor fluorescence imaging. MDH
      staining does not apparently affect LD trafficking, and the dye is
      extraordinarily photo-stable. Taken together MDH represents a reliable tool to
      use for the investigation of dynamic LD regulation within living cells using
      fluorescence microscopy.

PMID- 22396790
TI  - Role of oxidative stress and apoptosis in the placental pathology of Plasmodium
      berghei infected mice.
AB  - Placental malaria is a common clinical complication during pregnancy and is
      associated with abortion, premature delivery, intrauterine growth retardation and
      low birth weight. The present study was designed to delineate the underlying
      mechanism of placental pathology during malarial infection with special reference
      to oxidative stress and apoptosis. Experimentally, pregnant BALB/c mice were
      infected with Plasmodium berghei infected red blood cells on gestation day 10.
      The presence of malarial infection in placenta was confirmed by histopathological
      studies. It was observation that infected placenta had plugged placental
      sinusoids with parasitized red blood cells and malarial pigments. Interestingly,
      we found significant increase in the level of malondialdehyde, the index of
      oxidative stress and decreased activity of catalase, the antioxidant in infected
      placenta. Furthermore, in infected placenta the oxidative stress mediated
      apoptosis was determined by DNA fragmentation assay, ethidium bromide/acridine
      orange staining and caspase activity. It was observed that oxidative stress begin
      after second day of malarial infection. Interestingly, it was observed that there
      was down regulation of anti-apoptotic protein Bcl-2 and up regulation of pro
      apoptotic protein Bax in infected placenta, suggesting the involvement of
      mitochondrial pathway of apoptosis which was further confirmed by activation of
      caspase 9. However, no change in the expression of Fas gene and caspase 8
      activity, indicated the absence of death receptor pathway. Thus, it can be
      concluded that the placental pathology during malarial infection is mediated by
      mitochondrial pathway of apoptosis occurring due to augmented lipid peroxidation
      which may in turn jeopardise the materno-fetal relationship.

PMID- 22396791
TI  - Feeder cells support the culture of induced pluripotent stem cells even after
      chemical fixation.
AB  - Chemically fixed mouse embryonic fibroblasts (MEFs), instead of live feeder
      cells, were applied to the maintenance of mouse induced pluripotent stem (miPS)
      cells. Formaldehyde and glutaraldehyde were used for chemical fixation. The
      chemically fixed MEF feeders maintained the pluripotency of miPS cells, as well
      as their undifferentiated state. Furthermore, the chemically fixed MEF feeders
      were reused several times without affecting their functions. These results
      indicate that chemical fixation can be applied to modify biological feeders
      chemically, without losing their original functions. Chemically fixed MEF feeders
      will be applicable to other stem cell cultures as a reusable extracellular matrix
      candidate that can be preserved on a long-term basis.

PMID- 22396792
TI  - Is opium a real risk factor for esophageal cancer or just a methodological
      artifact? Hospital and neighborhood controls in case-control studies.
AB  - BACKGROUND: Control selection is a major challenge in epidemiologic case-control
      studies. The aim of our study was to evaluate using hospital versus neighborhood
      control groups in studying risk factors of esophageal squamous cell carcinoma
      (ESCC). METHODOLOGY/PRINCIPAL FINDINGS: We compared the results of two different
      case-control studies of ESCC conducted in the same region by a single research
      group. Case definition and enrollment were the same in the two studies, but
      control selection differed. In the first study, we selected two age- and sex
      matched controls from inpatient subjects in hospitals, while for the second we
      selected two age- and sex-matched controls from each subject's neighborhood of
      residence. We used the test of heterogeneity to compare the results of the two
      studies. We found no significant differences in exposure data for tobacco-related
      variables such as cigarette smoking, chewing Nass (a tobacco product) and hookah
      (water pipe) usage, but the frequency of opium usage was significantly different
      between hospital and neighborhood controls. Consequently, the inference drawn for
      the association between ESCC and tobacco use did not differ between the studies,
      but it did for opium use. In the study using neighborhood controls, opium use was
      associated with a significantly increased risk of ESCC (adjusted OR 1.77, 95% CI
      1.17-2.68), while in the study using hospital controls, this was not the case (OR
      1.09, 95% CI 0.63-1.87). Comparing the prevalence of opium consumption in the two
      control groups and a cohort enrolled from the same geographic area suggested that
      the neighborhood controls were more representative of the study base population
      for this exposure. CONCLUSIONS/SIGNIFICANCE: Hospital and neighborhood controls
      did not lead us to the same conclusion for a major hypothesized risk factor for
      ESCC in this population. Our results show that control group selection is
      critical in drawing appropriate conclusions in observational studies.

PMID- 22396793
TI  - Down-regulation of Yes Associated Protein 1 expression reduces cell proliferation
      and clonogenicity of pancreatic cancer cells.
AB  - BACKGROUND: The Hippo pathway regulates organ size by inhibiting cell
      proliferation and promoting cell apoptosis upon its activation. The Yes
      Associated Protein 1 (YAP1) is a nuclear effector of the Hippo pathway that
      promotes cell growth as a transcription co-activator. In human cancer, the YAP1
      gene was reported as amplified and over-expressed in several tumor types.
      METHODS: Immunohistochemical staining of YAP1 protein was used to assess the
      expression of YAP1 in pancreatic tumor tissues. siRNA oligonucleotides were used
      to knockdown the expression of YAP1 and their effects on pancreatic cancer cells
      were investigated using cell proliferation, apoptosis, and anchorage-independent
      growth assays. The Wilcoxon signed-rank, Pearson correlation coefficient,
      Kendall's Tau, Spearman's Rho, and an independent two-sample t (two-tailed) test
      were used to determine the statistical significance of the data. RESULTS:
      Immunohistochemistry studies in pancreatic tumor tissues revealed YAP1 staining
      intensities were moderate to strong in the nucleus and cytoplasm of the tumor
      cells, whereas the adjacent normal epithelial showed negative to weak staining.
      In cultured cells, YAP1 expression and localization was modulated by cell
      density. YAP1 total protein expression increased in the nuclear fractions in BxPC
      3 and PANC-1, while it declined in HPDE6 as cell density increased. Additionally,
      treatment of pancreatic cancer cell lines, BxPC-3 and PANC-1, with YAP1-targeting
      siRNA oligonucleotides significantly reduced their proliferation in vitro.
      Furthermore, treatment with YAP1 siRNA oligonucleotides diminished the anchorage
      independent growth on soft agar of pancreatic cancer cells, suggesting a role of
      YAP1 in pancreatic cancer tumorigenesis. CONCLUSIONS: YAP1 is overexpressed in
      pancreatic cancer tissues and potentially plays an important role in the
      clonogenicity and growth of pancreatic cancer cells.

PMID- 22396794
TI  - A comprehensive investigation on common polymorphisms in the MDR1/ABCB1
      transporter gene and susceptibility to colorectal cancer.
AB  - ATP Binding Cassette B1 (ABCB1) is a transporter with a broad substrate
      specificity involved in the elimination of several carcinogens from the gut.
      Several polymorphic variants within the ABCB1 gene have been reported as
      modulators of ABCB1-mediated transport. We investigated the impact of ABCB1
      genetic variants on colorectal cancer (CRC) risk. A hybrid tagging/functional
      approach was performed to select 28 single nucleotide polymorphisms (SNPs) that
      were genotyped in 1,321 Czech subjects, 699 CRC cases and 622 controls. In
      addition, six potentially functional SNPs were genotyped in 3,662 German
      subjects, 1,809 cases and 1,853 controls from the DACHS study. We found that
      three functional SNPs (rs1202168, rs1045642 and rs868755) were associated with
      CRC risk in the German population. Carriers of the rs1202168_T and rs868755_T
      alleles had an increased risk for CRC (P(trend) = 0.016 and 0.029, respectively),
      while individuals bearing the rs1045642_C allele showed a decreased risk of CRC
      (P(trend) = 0.022). We sought to replicate the most significant results in an
      independent case-control study of 3,803 subjects, 2,169 cases and 1,634 controls
      carried out in the North of Germany. None of the SNPs tested were significantly
      associated with CRC risk in the replication study. In conclusion, in this study
      of about 8,800 individuals we show that ABCB1 gene polymorphisms play at best a
      minor role in the susceptibility to CRC.

PMID- 22396795
TI  - Identification of the neogenin-binding site on the repulsive guidance molecule A.
AB  - Repulsive guidance molecule (RGM) is a membrane-bound protein that was originally
      identified as an axon guidance molecule in the chick retinotectal system. RGMa,
      one of the 3 isoforms found in mammals, is involved in laminar patterning,
      cephalic neural tube closure, axon guidance, and inhibition of axonal
      regeneration. In addition to its roles in the nervous system, RGMa plays a role
      in enhancing helper T-cell activation. Binding of RGM to its receptor, neogenin,
      is considered necessary to transduce these signals; however, information on the
      binding of RGM to neogenin is limited. Using co-immunoprecipitation studies, we
      have identified that the RGMa region required for binding to neogenin contains
      amino acids (aa) 259-295. Synthesized peptide consisting of aa 284-293 directly
      binds to the extracellular domain (ECD) of recombinant neogenin, and addition of
      this peptide inhibits RGMa-induced growth cone collapse in mouse cortical
      neurons. Thus, we propose that this peptide is a promising lead in finding
      reagents capable of inhibiting RGMa signaling.

PMID- 22396796
TI  - Placement of leucine zipper motifs at the carboxyl terminus of HIV-1 protease
      significantly reduces virion production.
AB  - Natural HIV-1 protease (PR) is homodimeric. Some researchers believe that
      interactions between HIV-1 Gag-Pol molecules trigger the activation of embedded
      PR (which mediates Gag and Gag-Pol cleavage), and that Gag-Pol assembly domains
      outside of PR may contribute to PR activation by influencing PR dimer interaction
      in a Gag-Pol context. To determine if the enhancement of PR dimer interaction
      facilitates PR activation, we placed single or tandem repeat leucine zippers (LZ)
      at the PR C-terminus, and looked for a correlation between enhanced Gag
      processing efficiency and increased Gag-PR-LZ multimerization capacity. We found
      significant reductions in virus-like particles (VLPs) produced by HIV-1 mutants,
      with LZ fused to the end of PR as a result of enhanced Gag cleavage efficiency.
      Since VLP production can be restored to wt levels following PR activity
      inhibition, this assembly defect is considered PR activity-dependent. We also
      found a correlation between the LZ enhancement effect on Gag cleavage and
      enhanced Gag-PR multimerization. The results suggest that PR dimer interactions
      facilitated by forced Gag-PR multimerization lead to premature Gag cleavage,
      likely a result of premature PR activation. Our conclusion is that placement of a
      heterologous dimerization domain downstream of PR enhances PR-mediated Gag
      cleavage efficiency, implying that structural conformation, rather than the
      primary sequence outside of PR, is a major determinant of HIV-1 PR activation.

PMID- 22396797
TI  - Sensitivity of calcification to thermal stress varies among genera of massive
      reef-building corals.
AB  - Reductions in calcification in reef-building corals occur when thermal conditions
      are suboptimal, but it is unclear how they vary between genera in response to the
      same thermal stress event. Using densitometry techniques, we investigate
      reductions in the calcification rate of massive Porites spp. from the Great
      Barrier Reef (GBR), and P. astreoides, Montastraea faveolata, and M. franksi from
      the Mesoamerican Barrier Reef (MBR), and correlate them to thermal stress
      associated with ocean warming. Results show that Porites spp. are more sensitive
      to increasing temperature than Montastraea, with calcification rates decreasing
      by 0.40 g cm(-2) year(-1) in Porites spp. and 0.12 g cm(-2) year(-1) in
      Montastraea spp. for each 1 degrees C increase. Under similar warming trends, the
      predicted calcification rates at 2100 are close to zero in Porites spp. and
      reduced by 40% in Montastraea spp. However, these predictions do not account for
      ocean acidification. Although yearly mean aragonite saturation (Omega(ar)) at MBR
      sites has recently decreased, only P. astreoides at Chinchorro showed a reduction
      in calcification. In corals at the other sites calcification did not change,
      indicating there was no widespread effect of Omega(ar) changes on coral
      calcification rate in the MBR. Even in the absence of ocean acidification,
      differential reductions in calcification between Porites spp. and Montastraea
      spp. associated with warming might be expected to have significant ecological
      repercussions. For instance, Porites spp. invest increased calcification in
      extension, and under warming scenarios it may reduce their ability to compete for
      space. As a consequence, shifts in taxonomic composition would be expected in
      Indo-Pacific reefs with uncertain repercussions for biodiversity. By contrast,
      Montastraea spp. use their increased calcification resources to construct denser
      skeletons. Reductions in calcification would therefore make them more susceptible
      to both physical and biological breakdown, seriously affecting ecosystem function
      in Atlantic reefs.

PMID- 22396798
TI  - The responsiveness of TrkB to BDNF and antidepressant drugs is differentially
      regulated during mouse development.
AB  - BACKGROUND: Previous studies suggest that the responsiveness of TrkB receptor to
      BDNF is developmentally regulated in rats. Antidepressant drugs (AD) have been
      shown to increase TrkB signalling in the adult rodent brain, and recent findings
      implicate a BDNF-independent mechanism behind this phenomenon. When administered
      during early postnatal life, ADs produce long-lasting biochemical and behavioural
      alterations that are observed in adult animals. METHODOLOGY: We have here
      examined the responsiveness of brain TrkB receptors to BDNF and ADs during early
      postnatal life of mouse, measured as autophosphorylation of TrkB (pTrkB).
      PRINCIPAL FINDINGS: We found that ADs fail to induce TrkB signalling before
      postnatal day 12 (P12) after which an adult response of TrkB to ADs was observed.
      Interestingly, there was a temporally inverse correlation between the appearance
      of the responsiveness of TrkB to systemic ADs and the marked developmental
      reduction of BDNF-induced TrkB in brain microslices ex vivo. Basal p-TrkB status
      in the brain of BDNF deficient mice was significantly reduced only during early
      postnatal period. Enhancing cAMP (cyclic adenosine monophosphate) signalling
      failed to facilitate TrkB responsiveness to BDNF. Reduced responsiveness of TrkB
      to BDNF was not produced by the developmental increase in the expression of
      dominant-negative truncated TrkB.T1 because this reduction was similarly observed
      in the brain microslices of trkB.T1(-/-) mice. Moreover, postnatal AD
      administration produced long-lasting behavioural alterations observable in adult
      mice, but the responses were different when mice were treated during the time
      when ADs did not (P4-9) or did (P16-21) activate TrkB. CONCLUSIONS: We have found
      that ADs induce the activation of TrkB only in mice older than 2 weeks and that
      responsiveness of brain microslices to BDNF is reduced during the same time
      period. Exposure to ADs before and after the age when ADs activate TrkB produces
      differential long-term behavioural responses in adult mice.

PMID- 22396799
TI  - Corvid re-caching without 'theory of mind': a model.
AB  - Scrub jays are thought to use many tactics to protect their caches. For instance,
      they predominantly bury food far away from conspecifics, and if they must cache
      while being watched, they often re-cache their worms later, once they are in
      private. Two explanations have been offered for such observations, and they are
      intensely debated. First, the birds may reason about their competitors' mental
      states, with a 'theory of mind'; alternatively, they may apply behavioral rules
      learned in daily life. Although this second hypothesis is cognitively simpler, it
      does seem to require a different, ad-hoc behavioral rule for every caching and re
      caching pattern exhibited by the birds. Our new theory avoids this drawback by
      explaining a large variety of patterns as side-effects of stress and the
      resulting memory errors. Inspired by experimental data, we assume that re-caching
      is not motivated by a deliberate effort to safeguard specific caches from theft,
      but by a general desire to cache more. This desire is brought on by stress, which
      is determined by the presence and dominance of onlookers, and by unsuccessful
      recovery attempts. We study this theory in two experiments similar to those done
      with real birds with a kind of 'virtual bird', whose behavior depends on a set of
      basic assumptions about corvid cognition, and a well-established model of human
      memory. Our results show that the 'virtual bird' acts as the real birds did; its
      re-caching reflects whether it has been watched, how dominant its onlooker was,
      and how close to that onlooker it has cached. This happens even though it cannot
      attribute mental states, and it has only a single behavioral rule assumed to be
      previously learned. Thus, our simulations indicate that corvid re-caching can be
      explained without sophisticated social cognition. Given our specific predictions,
      our theory can easily be tested empirically.

PMID- 22396800
TI  - Poplar GTL1 is a Ca2+/calmodulin-binding transcription factor that functions in
      plant water use efficiency and drought tolerance.
AB  - Diminishing global fresh water availability has focused research to elucidate
      mechanisms of water use in poplar, an economically important species. A GT-2
      family trihelix transcription factor that is a determinant of water use
      efficiency (WUE), PtaGTL1 (GT-2 like 1), was identified in Populus tremula * P.
      alba (clone 717-IB4). Like other GT-2 family members, PtaGTL1 contains both N-
      and C-terminal trihelix DNA binding domains. PtaGTL1 expression, driven by the
      Arabidopsis thaliana AtGTL1 promoter, suppressed the higher WUE and drought
      tolerance phenotypes of an Arabidopsis GTL1 loss-of-function mutation (gtl1-4).
      Genetic suppression of gtl1-4 was associated with increased stomatal density due
      to repression of Arabidopsis STOMATAL DENSITY AND DISTRIBUTION1 (AtSDD1), a
      negative regulator of stomatal development. Electrophoretic mobility shift assays
      (EMSA) indicated that a PtaGTL1 C-terminal DNA trihelix binding fragment (PtaGTL1
      C) interacted with an AtSDD1 promoter fragment containing the GT3 box (GGTAAA),
      and this GT3 box was necessary for binding. PtaGTL1-C also interacted with a
      PtaSDD1 promoter fragment via the GT2 box (GGTAAT). PtaSDD1 encodes a protein
      with 60% primary sequence identity with AtSDD1. In vitro molecular interaction
      assays were used to determine that Ca(2+)-loaded calmodulin (CaM) binds to
      PtaGTL1-C, which was predicted to have a CaM-interaction domain in the first
      helix of the C-terminal trihelix DNA binding domain. These results indicate that,
      in Arabidopsis and poplar, GTL1 and SDD1 are fundamental components of stomatal
      lineage. In addition, PtaGTL1 is a Ca(2+)-CaM binding protein, which infers a
      mechanism by which environmental stimuli can induce Ca(2+) signatures that would
      modulate stomatal development and regulate plant water use.

PMID- 22396802
TI  - Candida dubliniensis: an appraisal of its clinical significance as a bloodstream
      pathogen.
AB  - A nine-year prospective study (2002-2010) on the prevalence of Candida
      dubliniensis among Candida bloodstream isolates is presented. The germ tube
      positive isolates were provisionally identified as C. dubliniensis by presence of
      fringed and rough colonies on sunflower seed agar. Subsequently, their identity
      was confirmed by Vitek2 Yeast identification system and/or by amplification and
      sequencing of the ITS region of rDNA. In all, 368 isolates were identified as C.
      dubliniensis; 67.1% came from respiratory specimens, 11.7% from oral swabs, 9.2%
      from urine, 3.8% from blood, 2.7% from vaginal swabs and 5.4% from other sources.
      All C. dubliniensis isolates tested by Etest were susceptible to voriconazole and
      amphotericin B. Resistance to fluconazole (>=8 ug/ml) was observed in 2.5% of C.
      dubliniensis isolates, 7 of which occurred between 2008-2010. Of note was the
      diagnosis of C. dubliniensis candidemia in 14 patients, 11 of them occurring
      between 2008-2010. None of the bloodstream isolate was resistant to fluconazole,
      while a solitary isolate showed increased MIC to 5-flucytosine (>32 ug/ml) and
      belonged to genotype 4. A review of literature since 1999 revealed 28 additional
      cases of C. dubliniensis candidemia, and 167 isolates identified from blood
      cultures since 1982. In conclusion, this study highlights a greater role of C.
      dubliniensis in bloodstream infections than hitherto recognized.

PMID- 22396801
TI  - Critical role of constitutive type I interferon response in bronchial epithelial
      cell to influenza infection.
AB  - Innate antiviral responses in bronchial epithelial cells (BECs) provide the first
      line of defense against respiratory viral infection and the effectiveness of this
      response is critically dependent on the type I interferons (IFNs). However the
      importance of the antiviral responses in BECs during influenza infection is not
      well understood. We profiled the innate immune response to infection with H3N2
      and H5N1 virus using Calu-3 cells and primary BECs to model proximal airway
      cells. The susceptibility of BECs to influenza infection was not solely dependent
      on the sialic acid-bearing glycoprotein, and antiviral responses that occurred
      after viral endocytosis was more important in limiting viral replication. The
      early antiviral response and apoptosis correlated with the ability to limit viral
      replication. Both viruses reduced RIG-I associated antiviral responses and
      subsequent induction of IFN-beta. However it was found that there was
      constitutive release of IFN-beta by BECs and this was critical in inducing late
      antiviral signaling via type I IFN receptors, and was crucial in limiting viral
      infection. This study characterizes anti-influenza virus responses in airway
      epithelial cells and shows that constitutive IFN-beta release plays a more
      important role in initiating protective late IFN-stimulated responses during
      human influenza infection in bronchial epithelial cells.

PMID- 22396804
TI  - Inaugural editorial.

PMID- 22396803
TI  - Establishment of an ES cell-derived murine megakaryocytic cell line, MKD1, with
      features of primary megakaryocyte progenitors.
AB  - Because of the scarcity of megakaryocytes in hematopoietic tissues, studying
      megakaryopoiesis heavily relies on the availability of appropriate cellular
      models. Here, we report the establishment of a new mouse embryonic stem (ES) cell
      derived megakaryocytic cell line, MKD1. The cells are factor-dependent, their
      cell surface immunophenotype and gene expression profile closely resemble that of
      primary megakaryocyte progenitors (MkPs) and they further differentiate along the
      megakaryocyte lineage upon valproic acid treatment. At a functional level, we
      show that ablation of SCL expression, a transcription factor critical for MkP
      maturation, leads to gene expression alterations similar to that observed in
      primary, Scl-excised MkPs. Moreover, the cell line is amenable to biochemical and
      transcriptional analyses, as we report for GpVI, a direct target of SCL. Thus,
      the MKD1 cell line offers a pertinent experimental model to study the cellular
      and molecular mechanisms underlying MkP biology and more broadly
      megakaryopoiesis.

PMID- 22396805
TI  - Ten years of a multidisciplinary diabetic foot team approach in Sao Paulo,
      Brazil.
AB  - Diabetes mellitus can cause devastating foot problems including loss of
      protective sensation with subsequent ulcerations and amputations. The natural
      history and pathophysiology of diabetic foot ulcers is best understood and
      managed by a multiprofessional team approach. The main factors for prevention and
      treatment of these devastating diabetic foot conditions are shown, with special
      attention to education of the patient. This approach decreases the morbidity of
      the disease, besides its economical and social feasibility.

PMID- 22396807
TI  - Reverse flow digital artery pedicle flap for closure of diabetic forefoot
      ulceration.
AB  - Digital artery pedicle flap is a useful surgical technique for coverage of
      plantar foot defects. For diabetic forefoot ulcers that are subject to recurrence
      despite consistent care, this flap can provide long-term durable closure. The
      authors provide a case report and overview of this innovative reconstructive
      procedure.

PMID- 22396806
TI  - Diabetic foot infections: a team-oriented review of medical and surgical
      management.
AB  - As the domestic and international incidence of diabetes and metabolic syndrome
      continues to rise, health care providers need to continue improving management of
      the long-term complications of the disease. Emergency department visits and
      hospital admissions for diabetic foot infections are increasingly commonplace,
      and a like-minded multidisciplinary team approach is needed to optimize patient
      care. Early recognition of severe infections, medical stabilization, appropriate
      antibiotic selection, early surgical intervention, and strategic plans for
      delayed reconstruction are crucial components of managing diabetic foot
      infections. The authors review initial medical and surgical management and staged
      surgical reconstruction of diabetic foot infections in the inpatient setting.

PMID- 22396808
TI  - Clinical significance of the isolation of Staphylococcus epidermidis from bone
      biopsy in diabetic foot osteomyelitis.
AB  - INTRODUCTION: Coagulase-negative staphylococci are considered as microorganisms
      with little virulence and usually as contaminants. In order to establish the role
      of Staphylococcus epidermidis as a pathogen in diabetic foot osteomyelitis, in
      addition to the isolation of the sole bacterium from the bone it will be
      necessary to demonstrate the histopathological changes caused by the infection.
      METHODS: A consecutive series of 222 diabetic patients with foot osteomyelitis
      treated surgically in the Diabetic Foot Unit at La Paloma Hospital (Las Palmas de
      Gran Canaria, Canary Islands, Spain) between 1 October 2002 and 31 October 2008.
      From the entire series including 213 bone cultures with 241 isolated organisms,
      we have analyzed only the 139 cases where Staphylococci were found. We analyzed
      several variables between the two groups: Staphylococcus aureus versus
      Staphylococcus epidermidis. RESULTS: Of the 134 patients included in this study,
      Staphlylococcus epidermidis was found as the sole bacterium isolated in 11 cases
      and accompanied by other bacteria in 12 cases. Staphlylococcus aureus was found
      as the sole bacterium isolated in 72 cases and accompanied by other bacteria in
      39 cases. Histopathological changes were found in the cases of osteomyelitis
      where Staphylococcus epidermidis was the sole bacterium isolated. Acute
      osteomyelitis was found to a lesser extent when Staphylococcus epidermidis was
      the sole bacterium isolated but without significant differences with the cases
      where Staphylococcus aureus was the sole bacterium isolated. CONCLUSION:
      Staphylococcus epidermidis should be considered as a real pathogen, not only a
      contaminant, in diabetic patients with foot osteomyelitis when the bacterium is
      isolated from the bone. No differences in the outcomes of surgical treatment have
      been found with cases which Staphlylococcus aureus was isolated.

PMID- 22396809
TI  - The impact of increasing body mass on peak and mean plantar pressure in
      asymptomatic adult subjects during walking.
AB  - INTRODUCTION: The implication of high peak plantar pressure on foot pathology in
      individuals both with and without diabetes has been recognized. The aim of this
      study was to investigate and clarify the relationship between increasing body
      mass and peak and mean plantar pressure in an asymptomatic adult population
      during walking. METHODS: Thirty adults without any relevant medical history,
      structural foot deformities or foot posture assessed as highly pronated or
      supinated, and within a normal body mass index range were included in the study.
      An experimental, same subjects, repeated measures design was used. Peak and mean
      plantar pressure were evaluated with the F-Scan in-shoe plantar pressure
      measurement system under four different loading conditions (0, 5, 10, and 15 kg)
      simulated with a weighted vest. Pressure data were gathered from three stances
      utilizing the mid-gait protocol. RESULTS: There were statistically significant
      increases in peak pressure between the 10 and 15 kg load conditions compared to
      the control (0 kg) within the heel and second to fifth metatarsal regions. The
      first metatarsal and hallux regions only displayed statistically significant
      increases in peak pressure between 15 kg and the control (0 kg). The midfoot and
      lesser digits regions did not display any statistically significant differences
      in peak pressure between any load conditions compared to the control (0 kg). The
      second to fifth metatarsal region displayed statistically significant increases
      in mean pressure in the 5, 10 and 15 kg groups compared to the control (0 kg). A
      statistically significant increase in peak pressure between the 15 kg and control
      (0 kg) group was evident in all other regions. CONCLUSION: The relationship
      between increasing body mass and peak and mean plantar pressure was dependent
      upon the plantar region. This study provides more detail outlining the response
      of peak and mean pressure to different loading conditions than previously
      reported in the literature. Further research including measurement of temporal
      parameters is warranted.

PMID- 22396810
TI  - Value of team approach combined with clinical pathway for diabetic foot problems:
      a clinical evaluation.
AB  - AIMS: To evaluate the effectiveness of management of diabetic foot problems (DFP)
      by the National University Hospital (NUH) Multidisciplinary Diabetic Foot Team
      combined with a clinical pathway in terms of average length of stay (ALOS),
      readmission rates, hospitalisation cost per patient, major reamputation rate, and
      complication rate. METHODS: 939 patients admitted to the Department of
      Orthopaedic Surgery, NUH, for DFP from 2002 (before team formation) to 2007
      (after team formation). It consisted of six cohorts of patients - 61 for 2002, 70
      for 2003, 148 for 2004, 180 for 2005, 262 for 2006, and 218 for 2007. All
      patients were managed by the NUH Multidisciplinary Diabetic Foot Team combined
      with a clinical pathway. Statistical analyses were carried out for five
      parameters (ALOS, hospitalisation cost per patient, major amputation rate,
      readmission rate, and complication rate). RESULTS: From 2002 to 2007, the ALOS
      was significantly reduced from 20.36 days to 12.20 days (p=0.0005). Major
      amputation rate was significantly reduced from 31.15 to 11.01% (p<0.0005). There
      was also a significant reduction in complication rate from 19.67 to 7.34%
      (p=0.005). There were reductions in the hospitalisation cost per patient and
      readmission rate after formation of the multidisciplinary team but they were not
      statistically significant. CONCLUSION: Our evaluation showed that a
      multidisciplinary team approach combined with the implementation of a clinical
      pathway in NUH was effective in reducing the ALOS, major amputation rate, and
      complication rate of DFP.

PMID- 22396811
TI  - The role of an extended medial column arthrodesis for Charcot midfoot
      neuroarthropathy.
AB  - The etiology of diabetic Charcot neuroarthropathy involving the midfoot often
      includes an inciting traumatic event or repetitive micro-trauma from an
      uncompensated biomechanical imbalance that potentiates an incompletely understood
      pathway leading to a rocker-bottom foot deformity and ulceration. In the setting
      of a severe Charcot foot fracture and/or dislocation with obvious osseous
      instability, diagnostic delay can potentiate the limb-threatening sequelae of
      infected midfoot ulcerations in this patient population. In this article, the
      authors discuss the thought process as well as the advantages of performing an
      extended medial column arthrodesis for selected Charcot midfoot deformities.

PMID- 22396812
TI  - Combined circular external fixation and open reduction internal fixation with pro
      syndesmotic screws for repair of a diabetic ankle fracture.
AB  - The surgical management of ankle fractures among the diabetic population is
      associated with higher complication rates compared to the general population.
      Efforts toward development of better methods in prevention and treatment are
      continuously evolving for these injuries. The presence of peripheral neuropathy
      and the possible development of Charcot neuroarthropathy in this high risk
      patient population have stimulated much surgical interest to create more stable
      osseous constructs when open reduction of an ankle fracture/dislocation is
      required. The utilization of multiple syndesmotic screws (pro-syndesmotic screws)
      to further stabilize the ankle mortise has been reported by many foot and ankle
      surgeons. In addition, transarticular Steinmann pins have been described as an
      adjunct to traditional open reduction with internal fixation (ORIF) of the ankle
      to better stabilize the talus, thus minimizing risk of further displacement,
      malunion, and Charcot neuroarthropathy. The authors present a unique technique of
      ORIF with pro-syndesmotic screws and the application of a multi-plane circular
      external fixator for management of a neglected diabetic ankle fracture that
      prevented further deformity while allowing a weight-bearing status. This techniqu
      may be utilized for the management of complex diabetic ankle fractures that are
      prone to future complications and possible limb loss.

PMID- 22396813
TI  - Surgical management of a diabetic calcaneal ulceration and osteomyelitis with a
      partial calcanectomy and a sural neurofasciocutaneous flap.
AB  - The treatment of calcaneal osteomyelitis in diabetic patients poses a great
      challenge to the treating physician and surgeon. The use of a distally based
      sural neurofasciocutaneous flap after an aggressive debridement of non-viable and
      poorly vascularized tissue and bone that is combined with a thorough antibiotic
      regimen provides a great technique for adequate soft tissue coverage of the heel.
      In this case report, the authors describe the aforementioned flap as a versatile
      alternative to the use of local or distant muscle flaps for diabetic patients
      with calcaneal osteomyelitis and concomitant large wounds.

PMID- 22396815
TI  - Foreword.

PMID- 22396814
TI  - Socioeconomic profile of diabetic patients with and without foot problems.
AB  - INTRODUCTION: To identify the differences in a socioeconomic profile between two
      cohorts of diabetic patients - one with diabetic foot problems and another
      without diabetic foot problems. MATERIALS AND METHODS: The cohort with diabetic
      foot problems (including cellulitis, abscess, osteomyelitis, septic arthritis,
      gangrene, ulcers, or Charcot joint disease) consisted of 122 diabetic patients,
      while the other cohort without foot problems consisted of 112 diabetic patients.
      Both were seen at the National University Hospital from January to April 2007. A
      detailed protocol was designed and the factors studied included patient profile,
      average monthly household income, education, compliance to diabetic medication,
      attendance at clinics for diabetic treatment, exercise, smoking, alcohol
      consumption, gender, and glycosylated haemoglobin (HbA1(C)) level. These were
      studied for significant differences using univariate and stepwise multivariate
      logistic regression analysis. RESULTS: With multivariate analysis, Malay
      ethnicity (p<0.001), education of up to secondary school only (p=0.021), low
      average monthly household income of less than SGD $2,000 (p=0.030), lack of
      exercise (at least once a week, p=0.04), and elevated HbA1(C) level (>7.0%;
      p=0.015) were found to be significantly higher in the cohort with diabetic foot
      problems than the cohort without. CONCLUSIONS: There are significant differences
      in the socioeconomic factors between diabetic patients with diabetic foot
      problems and those without.

PMID- 22396816
TI  - Management of diabetic neuropathic foot and ankle malunions and nonunions.
AB  - The management of diabetic neuropathic foot and ankle malunions and/or nonunions
      is often complicated by the presence of broken or loosened hardware, Charcot
      joints, infection, osteomyelitis, avascular bone necrosis, unstable deformities,
      bone loss, disuse and pathologic osteopenia, and ulcerations. The author
      discusses a rational approach to functional limb salvage with various surgical
      techniques that are aimed at achieving anatomic alignment, long-term osseous
      stability, and adequate soft tissue coverage. Emphasis is placed on techniques to
      overcome the inherent challenges that are encountered when surgically managing a
      diabetic nonunion and/or malunion. Particular attention is directed to the
      management of deep infection and Charcot neuroarthropathy in the majority of the
      cases presented.

PMID- 22396817
TI  - The use of a combined bipedicled axial perforator based fasciocutaneous flap for
      the treatment of a traumatic diabetic foot wound: a case report.
AB  - The axial and perforator vascularised fasciocutaneous flaps are reliable and
      effective treatment methods for covering lower limb post-traumatic, septic,
      Charcot, and diabetic foot wounds. The authors describe the unique utilisation of
      a hybrid flap as an axial-perforator flap combination for the treatment of a
      traumatic diabetic foot wound.

PMID- 22396818
TI  - Recurrence of diabetic pedal ulcerations following tendo-achilles lengthening.
AB  - Foot and ankle surgeons are frequently challenged by the devastating systemic
      consequences of diabetes mellitus manifested through neuropathy, integumentary
      and joint breakdown, delayed healing, decreased ability to fight infection, and
      fragile tendon/ligaments. Diabetic neuropathic pedal ulcerations lead to
      amputations at an alarming rate and also carry a high mortality rate. This
      article will discuss causes of diabetic pedal ulcerations that persist or recur
      after tendo-Achilles lengthening and will highlight areas that need to be
      addressed by the practitioner such as infection, vascular and nutritional status,
      glucose control, off-loading, biomechanics, and patient compliance.

PMID- 22396819
TI  - Assessment of sensory neuropathy in patients with diabetic foot problems.
AB  - Our aim of this study was to compare the accuracy of three different modalities
      for testing sensory neuropathy in diabetic patients with and without diabetic
      foot problems. The three devices used included the pin-prick testing using the
      Neurotip(r) (PPT), the Semmes-Weinstein 5.07/10 g monofilament testing (SWMT),
      and the rapid-current perception threshold (R-CPT) measurements using the
      Neurometer(r) testing. Our study population consisted of 54 patients (108 feet)
      with diabetic foot problems treated at the National University Hospital in
      Singapore by our multi-disciplinary diabetic foot care team. Our results showed
      no difference in sensory neuropathy detected by PPT and 5.07/10 g SWMT in both
      the pathological and normal foot. In the pathological foot, there was significant
      increase in sensory neuropathy detected by the Neurometer(r) device at both the
      big toe and ankle sites as compared to PPT and 5.07/10 g SWMT. In the normal
      foot, there was a significant increase in sensory neuropathy detected by the
      Neurometer(r) device at the big toe site only as compared to PPT and 5.07/10 g
      SWMT. Finally, the Neurometer(r) measurements detected a statistically higher
      proportion of feet with sensory neuropathy as compared to detection by the PPT or
      5.07/10 g SWMT.

PMID- 22396821
TI  - Abductor hallucis muscle flap with circular external fixation for Charcot foot
      osteomyelitis: a case report.
AB  - Complicated soft tissue defects of the diabetic foot often call for alternative
      methods to traditional primary closure. Despite the popularity of microvascular
      free flaps, local muscle flaps can offer reliable reconstruction for these
      challenging wounds with shorter surgical times and reduced complication rates. In
      this article, the authors describe the successful use of the abductor hallucis
      muscle flap and external fixation for soft tissue reconstruction of a chronic
      Charcot foot wound and osteomyelitis in a diabetic patient.

PMID- 22396820
TI  - Distal posterior tibial artery perforator flaps for the management of calcaneal
      and Achilles tendon injuries in diabetic and non-diabetic patients.
AB  - Management of Achilles tendon and heel area defects is a common challenge for the
      reconstructive surgeon due to the lack of soft tissue availability in that
      region. In this article, we present our experience in covering these defects by
      using the distal perforator propeller flaps based on the posterior tibial artery.
      Perforator flaps are based on cutaneous, small diameter vessels that originate
      from a main pedicle and perforate the fascia or muscle to reach the skin. Their
      development has followed the understanding of the blood supply from a source
      artery to the skin. Six patients (five males and one female) underwent
      reconstruction by using the posterior tibial artery distal perforator flap for
      covering defects in the distal Achilles tendon region in patients with and
      without diabetes mellitus. Postoperative complications included a hypertrophic
      scar formation in one patient, partial marginal flap necrosis in another patient,
      and a wound infection in a third patient. All wounds were eventually healed by
      the last postoperative visit. In conclusion, perforator flaps based on the distal
      posterior tibial artery may be a reliable option for the coverage of small to
      moderate size defects of the Achilles tendon and heel area regions.

PMID- 22396823
TI  - The use of Papineau technique for the treatment of diabetic and non-diabetic
      lower extremity pseudoarthrosis and chronic osteomyelitis.
AB  - The treatment of 31 consecutive adult patients, ages 25-67 years with chronic
      draining osteomyelitis (12 cases) or infected pseudarthrosis (19 cases) by the
      Papineau technique was retrospectively reviewed. The initial injury was an open
      fracture in 24 patients and a closed fracture in 7 patients. In all cases an
      Ilizarov circular external fixation device was used for the stabilization of the
      fracture or for bone lengthening. Mean follow-up for the group was 20 months
      (range, 10 months to 5 years) and there was successful limb salvage in all cases
      with eradication of infection and bone consolidation was achieved. The Ilizarov
      circular external fixation was removed at a mean of 18 weeks (range, 14-24
      weeks). The mean time to bone union was 5 months (range, 4-10 months). All
      patients returned to their pre-treatment activity levels or better.

PMID- 22396822
TI  - Dressing plantar wounds with foam dressings, is it too much pressure?
AB  - Diabetes and its associated complications have become a major concern locally,
      nationally and internationally. One such complication is lower extremity
      amputation, commonly preceded by chronic ulceration. The cause of this tissue
      breakdown is multi-faceted, but includes an increase in pressure, particularly
      plantar pressure. As such, the choice of dressing to be applied to a plantar
      wound should ideally not increase this pressure further. A commonly used and
      possibly more bulky dressing is the foam dressing. This pilot study investigates
      the plantar pressures associated with three common foam dressings (Allevyn((r)),
      Lyofoam((r)) and Mepilex((r))) compared with a control dressing (Melolin((r))).
      Twelve healthy males and 19 females [SD] age 36.6 [10.4] were measured using the
      F-scan plantar pressure measurement system. Substantial variations in individual
      pressure changes occurred across the foot. No significant differences were
      identified, once a Bonferroni correction was applied. In healthy adults, it could
      be concluded that foam dressings do not have any effect on the plantar pressures
      of the foot. However, the need remains for a robust trial on a pathological
      population.

PMID- 22396824
TI  - Predictive factors for lower extremity amputations in diabetic foot infections.
AB  - The objective of this study was to evaluate the epidemiology of diabetic foot
      infections (DFIs) and its predictive factors for lower extremity amputations. A
      prospective study of 100 patients with DFIs treated at the National University
      Hospital of Singapore were recruited in the study during the period of January
      2005-June 2005. A protocol was designed to document patient's demographics, type
      of DFI, presence of neuropathy and/or vasculopathy and its final outcome.
      Predictive factors for limb loss were determined using univariate and stepwise
      logistic regression analysis. The mean age of the study population was 59.8 years
      with a male to female ratio of about 1:1 and with a mean follow-up duration of
      about 24 months. All patients had type 2 diabetes mellitus. Common DFIs included
      abscess (32%), wet gangrene (29%), infected ulcers (19%), osteomyelitis (13%),
      necrotizing fasciitis (4%) and cellulitis (3%). Thirteen patients were treated
      conservatively, while surgical debridement or distal amputation was performed in
      59 patients. Twenty-eight patients had major amputations (below or above knee)
      performed. Forty-eight percent had monomicrobial infections compared with 52%
      with polymicrobial infections. The most common pathogens found in all infections
      (both monomicrobial and polymicrobial) were Staphylococcus aureus (39.7%),
      Bacteroides fragilis (30.3%), Pseudomonas aeruginosa (26.0%) and Streptococcus
      agalactiae (21.0%). Significant univariate predictive factors for limb loss
      included age above 60 years, gangrene, ankle-brachial index (ABI) <0.8,
      monomicrobial infections, white blood cell (WBC) count >= 15.0*10(9)/L,
      erythrocyte sedimentation rate >=100 mm/hr, C-reactive protein >=15.0 mg/dL,
      hemoglobin (Hb) <=10.0g/dL and creatinine >=150 umol/L. Upon stepwise logistic
      regression, only gangrene, ABI <0.8, WBC >= 15.0*10(9)/L and Hb <=10.0g/dL were
      significant.

PMID- 22396825
TI  - Effectiveness of bridge V.A.C. dressings in the treatment of diabetic foot
      ulcers.
AB  - OBJECTIVES: This is a prospective study of the clinical efficacy of the V.A.C.
      Granufoam Bridge Dressing for the treatment of diabetic foot ulcers. MATERIALS
      AND METHODS: Five consecutive patients with diabetic foot ulcers were treated
      with V.A.C. Granufoam Bridge Dressings and studied over a period of 22-48 days.
      The indications for treatment included diabetic patients with open ray amputation
      wounds and wounds post-drainage for abscess with exposed deep structures.
      Clinical outcome was measured in terms of reduction in wound dimensions, presence
      of wound granulation, microbial clearance, and development of wound
      complications. RESULTS: Our results showed that with V.A.C. therapy, wound
      healing occurred in all patients. The number of dressings required ranged from 8
      to 10. The baseline average wound size was 23.1 cm(2). Wound areas shrunk by 18.4
      41.7%. All subjects achieved 100% wound bed granulation with an average length of
      treatment of 33 days. Microbial clearance was achieved in all cases. All wounds
      healed by secondary intention in one case and four cases required split-thickness
      skin grafting. CONCLUSION: The V.A.C. Granufoam Bridge Dressing is effective in
      the treatment of diabetic foot ulcers. It promotes reduction of wound area, wound
      bed granulation, and microbial clearance. By allowing placement of the suction
      pad outside the foot, it allowed patients to wear protective shoes and to walk
      non-weight bearing with crutches during V.A.C. therapy.

PMID- 22396826
TI  - The reverse sural fasciocutaneous flap for the treatment of traumatic, infectious
      or diabetic foot and ankle wounds: A retrospective review of 16 patients.
AB  - The authors present their experience with the use of sural fasciocutaneous flaps
      for the treatment of various soft tissue defects in the lower limb. This paper is
      a review of these flaps carried out between 2003 and 2008. The series consists of
      16 patients, 11 men and 5 women with an average age of 41 years (17-81) and with
      a follow-up period between 2 and 7 years. The etiology was major velocity
      accident in six cases, diabetes mellitus with osteomyelitis after ORIF for
      fractures (2), work accident in five, and another two cases with complications of
      lower limb injuries. The defect areas were located on calcaneus, malleolar area,
      tarsal area and lower tibia. Associated risk factors in the patients for the flap
      performance were diabetes (five patients) and cigarette smoking (ten
      patients).The technique is based on the use of a reverse-flow island sural flap
      combined with other flaps in three cases (cross-leg, peroneal, gastrocnemius).
      The anatomical structures which constituted the pedicle were the superficial and
      deep fascia, the sural nerve, the lesser saphenous vein and skin.The flap was
      viable in all 15 patients. On 8 cases was achieved direct closure, on three cases
      occurred a superficial necrosis and was skin grafted, on one case was observed
      partial necrosis which was treated with a second flap (posterior tibial
      perforator flap) and another one occurred delayed skin healing.The sural
      fasciocutaneous flap is useful for the treatment of severe and complex injuries
      and their complications in diabetic and non diabetic lower limbs. Its technical
      advantages are easy dissection, preservation of more important vascular
      structures in the limb and complete coverage of the soft tissue defects in just
      one operation without the need of microsurgical anastomosis. Thus this flap
      offers excellent donor sites for repairing soft tissue defects in foot and ankle.

PMID- 22396827
TI  - A systematic approach to the failed plastic surgical reconstruction of the
      diabetic foot.
AB  - Plastic reconstruction for diabetic foot wounds must be approached carefully and
      follow sound micro-surgical principles as it relates to the anatomy of the
      designated flap chosen for coverage. First, the surgeon always needs to evaluate
      the local and general conditions of the presenting pathology and patient,
      respectively when considering a flap for reconstruction. The flap that is chosen
      is based on the vascularity, location, and size of the defect. Salvage of the
      failed flap and revisional reconstructive procedures are very challenging. Often,
      adjunctive therapies such as hyperbaric oxygen, negative pressure wound therapy,
      vasodilators, and/or vascular surgery is required. In certain case scenarios,
      such as patients with poor general health and compromised local vascularity in
      which revisional flap coverage cannot be performed, the above mentioned
      adjunctive therapies could be used as a primary treatment to potentially salvage
      a failing flap.

PMID- 22396828
TI  - Erratum:.
AB  - [This corrects the article DOI: 10.3402/dfa.v2i0.10207.].

PMID- 22396829
TI  - German-Austrian consensus on operative treatment of Charcot neuroarthropathy: a
      Perspective by the Charcot task force of the German Association for Foot Surgery.

PMID- 22396830
TI  - Minimally invasive surgery for diabetic plantar foot ulcerations.
AB  - Complications of diabetes mellitus constitute the most common indications for
      hospitalization and non-traumatic amputations in the USA. The most important risk
      factors for the development of diabetic foot ulcerations include the presence of
      peripheral neuropathy, vasculopathy, limited joint mobility, and pre-existing
      foot deformities. In our study, 500 diabetic patients treated for plantar
      forefoot ulcerations were enrolled in a prospective study from 2000 to 2008 at
      the Federal University of Sao Paulo, Brazil. Fifty-two patients in the study met
      the criteria and underwent surgical treatment consisting of percutaneous Achilles
      tendon lengthening to treat plantar forefoot ulcerations. The postoperative
      follow-up demonstrated prevention of recurrent foot ulcerations in 92% of these
      diabetic patients that maintained an improved foot function. In conclusion, our
      study supports that identification and treatment of ankle equinus in the diabetic
      population may potentially lead to decreased patient morbidity, including reduced
      risk for both reulceration, and potential lower extremity amputation.

PMID- 22396831
TI  - An overview of conservative treatment options for diabetic Charcot foot
      neuroarthropathy.
AB  - Conservative management of Charcot foot neuroarthropathy remains efficacious for
      certain clinical scenarios. Treatment of the patient should take into account the
      stage of the Charcot neuroarthopathy, site(s) of involvement, presence or absence
      of ulceration, presence or absence of infection, overall medical status, and
      level of compliance. The authors present an overview of evidence-based non
      operative treatment for diabetic Charcot neuroarthropathy with an emphasis on the
      most recent developments in therapy.

PMID- 22396832
TI  - Incidence of re-amputation following partial first ray amputation associated with
      diabetes mellitus and peripheral sensory neuropathy: a systematic review.
AB  - Diabetes mellitus with peripheral sensory neuropathy frequently results in
      forefoot ulceration. Ulceration at the first ray level tends to be recalcitrant
      to local wound care modalities and off-loading techniques. If healing does occur,
      ulcer recurrence is common. When infection develops, partial first ray amputation
      in an effort to preserve maximum foot length is often performed. However, the
      survivorship of partial first ray amputations in this patient population and
      associated re-amputation rate remain unknown. Therefore, in an effort to
      determine the actual re-amputation rate following any form of partial first ray
      amputation in patients with diabetes mellitus and peripheral neuropathy, the
      authors conducted a systematic review. Only studies involving any form of partial
      first ray amputation associated with diabetes mellitus and peripheral sensory
      neuropathy but without critical limb ischemia were included. Our search yielded a
      total of 24 references with 5 (20.8%) meeting our inclusion criteria involving
      435 partial first ray amputations. The weighted mean age of patients was 59 years
      and the weighted mean follow-up was 26 months. The initial amputation level
      included the proximal phalanx base 167 (38.4%) times; first metatarsal head
      resection 96 (22.1%) times; first metatarsal-phalangeal joint disarticulation 53
      (12.2%) times; first metatarsal mid-shaft 39 (9%) times; hallux fillet flap 32
      (7.4%) times; first metatarsal base 29 (6.7%) times; and partial hallux 19 (4.4%)
      times. The incidence of re-amputation was 19.8% (86/435). The end stage, most
      proximal level, following re-amputation was an additional digit 32 (37.2%) times;
      transmetatarsal 28 (32.6%) times; below-knee 25 (29.1%) times; and LisFranc 1
      (1.2%) time. The results of our systematic review reveal that one out of every
      five patients undergoing any version of a partial first ray amputation will
      eventually require more proximal re-amputation. These results reveal that partial
      first ray amputation for patients with diabetes and peripheral sensory neuropathy
      may not represent a durable, functional, or predictable foot-sparing amputation
      and that a more proximal amputation, such as a balanced transmetatarsal
      amputation, as the index amputation may be more beneficial to the patient.
      However, this remains a matter for conjecture due to the limited data available
      and, therefore, additional prospective investigations are warranted.

PMID- 22396833
TI  - Permanent antibiotic impregnated intramedullary nail in diabetic limb salvage: a
      case report and literature review.
AB  - Managing complications after attempted hind foot and ankle arthrodesis with
      intramedullary nail fixation is a challenge. This situation becomes more
      problematic in the patient with diabetes mellitus and multiple comorbidities.
      Infection and subsequent osteomyelitis can be a devastating, limb threatening
      complication associated with these procedures. The surgeon must manage both the
      infectious process and the skeletal instability concurrently. This article
      provides a literature review and detailed management strategies for a modified
      technique of employing antibiotic impregnated polymethylmethacrylate-coated
      intramedullary nailing.

PMID- 22396834
TI  - The pathogenesis of Charcot neuroarthropathy: current concepts.
AB  - The pathogenesis of Charcot neuroarthropathy (CN) has been poorly understood by
      clinicians and scientists alike. Current researchers have made progress toward
      understanding the cause of CN and possible treatment options. The authors review
      the current literature on the pathogenesis of this debilitating disorder and
      attempt to explain the roles of inflammation, bone metabolism, and advanced
      glycation end products.

PMID- 22396835
TI  - The role of stereotactic radiosurgery in metastasis to the spine.
AB  - OBJECTIVE: The incidence and prevalence of spinal metastases are increasing, and
      although the role of radiation therapy in the treatment of metastatic tumors of
      the spine has been well established, the same cannot be said about the role of
      stereotactic radiosurgery. Herein, the authors present a systematic review
      regarding the value of spinal stereotactic radiosurgery in the management of
      spinal metastasis. METHODS: A systematic literature search for stereotactic
      radiosurgery of spinal metastases was undertaken. Grades of Recommendation,
      Assessment, Development, and Education (GRADE) working group criteria was used to
      evaluate the qualities of study datasets. RESULTS: Thirty-one studies met the
      study inclusion criteria. Twenty-three studies were of low quality, and 8 were of
      very low quality according to the GRADE criteria. Stereotactic radiosurgery was
      reported to be highly effective in reducing pain, regardless of prior treatment.
      The overall local control rate was approximately 90%. Additional asymptomatic
      lesions may be treated by stereotactic radiosurgery to avoid further irradiation
      of neural elements and further bone-marrow suppression. Stereotactic radiosurgery
      may be preferred in previously irradiated patients when considering the radiation
      tolerance of the spinal cord. Furthermore, residual tumors after surgery can be
      safely treated by stereotactic radiosurgery, which decreases the likelihood of
      repeat surgery and accompanying surgical morbidities. Encompassing one vertebral
      body above and below the involved vertebrae is unnecessary. Complications
      associated with stereotactic radiosurgery are generally self-limited and mild.
      CONCLUSION: In the management of spinal metastasis, stereotactic radiosurgery
      appears to provide high rates of tumor control, regardless of histologic
      diagnosis, and can be used in previously irradiated patients. However, the
      quality of literature available on the subject is not sufficient.

PMID- 22396836
TI  - Clinical outcomes of percutaneous plasma disc coagulation therapy for lumbar
      herniated disc diseases.
AB  - OBJECTIVE: This is prospective study of clinical outcomes of percutaneous plasma
      disc coagulation Therapy (PDCT) in patients with herniated lumbar disc disease
      (HLD) to evaluate the safety and efficacy in its clinical application and
      usefulness as a reliable alternative to microscopic discectomy. METHODS: Forty
      six patients were enrolled in this study from April 2006 to June 2010. All
      patients had one-level HLD. Disc degeneration was graded on routine T2-weighted
      magnetic resonance Image (MRI) using the Pfirrmann's grading system and all index
      levels were grade 3 and grade 4. Indications for surgery were radiculopathy
      caused by disc protrusion with soft consistency. MRI was done at one month after
      the procedure in all patients to check post-PDCT change. The clinical outcomes
      were evaluated using Visual Analog Scales (VAS) score and MacNab's criteria.
      RESULTS: This study was approved by the Institutional Review Board of our
      institution. The age of the study population ranged from 16 to 59 years with a
      mean age of 37.2 years. There were 29 males and 17 females in this study. The
      mean period of clinical follow-up was 21 months. The average preoperative VAS
      score for radiculopathy was 7.4+/-1.4, while the final follow-up VAS score was
      1.4+/-0.7 (p<0.001). In MacNab's criteria, 41 patients (89.1%) had achieved
      favorable improvement (excellent and good) until later follow-up. There were one
      patient from infection and two patients who needed to convert to open discectomy.
      CONCLUSION: PDCT is a safe and efficient treatment modality in a selective
      patient with HLD.

PMID- 22396837
TI  - Direct pars repair surgery using two different surgical methods : pedicle screw
      with universal hook system and direct pars screw fixation in symptomatic lumbar
      spondylosis patients.
AB  - OBJECTIVE: The authors performed a retrospective study to assess the clinical and
      radiological outcome in symptomatic lumbar spondylolysis patients who underwent a
      direct pars repair surgery using two different surgical methods; pedicle screw
      with universal hook system (PSUH) and direct pars screw fixation (DPSF), and
      compared the results between two different treated groups. METHODS: Forty-seven
      consecutive patients (PSUH; 23, DPSF; 15) with symptomatic lumbar spondylolysis
      who underwent a direct pars repair surgery were included. The average follow-up
      period was 37 months in the PSUH group, and 28 months in the DPSF group. The
      clinical outcome was measured using visual analogue pain scale (VAS) and Oswestry
      disability index (ODI). The length of operation time, the amount of blood loss,
      the duration of hospital stay, surgical complications, and fusion status were
      also assessed. RESULTS: When compared to the DPSF group, the average preoperative
      VAS and ODI score of the PSUH group were less decreased at the last follow-up;
      (the PSUH group; back VAS : 4.9 vs. 3.0, leg VAS : 6.8 vs. 2.2, ODI : 50.6% vs.
      24.6%, the DPSF group; back VAS : 5.7 vs. 1.1, leg VAS : 6.1 vs. 1.2, ODI : 57.4%
      vs. 18.2%). The average operation time was 174.9 minutes in the PSUH group, and
      141.7 minutes in the DPSF group. The average blood loss during operation was
      468.8 cc in the PSUH group, and 298.8 cc in the DPSF group. The average hospital
      stay after operation was 8.9 days in the PSUH group, and 7 days in the DPSF
      group. In the PSUH group, there was one case of a screw misplacement requiring
      revision surgery. In the DPSF group, one patient suffered from transient leg
      pain. The successful bone fusion rate was 78.3% in the PSUH group, and 93.3% in
      the DPSF group. CONCLUSION: The present study suggests that the technique using
      direct pars screw would be more effective than the method using pedicle screw
      with lamina hook system, in terms of decreased operation time, amount of blood
      loss, hospital stay, and increased fusion success rate, as well as better
      clinical outcome.

PMID- 22396838
TI  - A comparison study on the change in lumbar lordosis when standing, sitting on a
      chair, and sitting on the floor in normal individuals.
AB  - OBJECTIVE: To compare radiographic analysis on the sagittal lumbar curve when
      standing, sitting on a chair, and sitting on the floor. METHODS: Thirty
      asymptomatic volunteers without a history of spinal pathology were recruited. The
      study population comprised 11 women and 19 men with a mean age of 29.8 years. An
      independent observer assessed whole lumbar lordosis (WL) and segmental lordosis
      (SL) between L1 and S1 using the Cobb's angle on lateral radiographs of the
      lumbar spine obtained from normal individuals when standing, sitting on a chair,
      and sitting on the floor. WL and SL at each segment were compared for each
      position. RESULTS: WL when sitting on the floor was reduced by 72.9% than the
      average of that in the standing position. Of the total decrease in WL, 78%
      occurred between L4 to S1. There were significant decreases in SL at all lumbar
      spinal levels, except L1-2, when sitting on the floor as compared to when
      standing and sitting on a chair. Changes in WL between the positions when sitting
      on a chair and when sitting on the floor were mostly contributed by the loss of
      SL at the L4-5 and L5-S1 levels. CONCLUSION: When sitting on the floor, WL is
      relatively low; this is mostly because of decreasing lordosis at the L4-5 and L5
      S1 levels. In the case of lower lumbar fusion, hyperflexion is expected at the
      adjacent segment when sitting on the floor. To avoid this, sitting with a
      lordotic lumbar curve is important. Surgeons should remember to create sufficient
      lordosis when performing lower lumbar fusion surgery in patients with an oriental
      life style.

PMID- 22396839
TI  - The prognostic factors related to traumatic brain stem injury.
AB  - OBJECTIVE: This study was conducted to assess the clinical significance of
      traumatic brain stem injury (TBSI) reflected on Glasgow Coma Score (GCS) and
      Glasgow Outcome Score (GOS) by various clinical variables. METHODS: A total of
      136 TBSI patients were selected out of 2695 head-injured patients. All initial
      computerized tomography and/or magnetic resonance imaging studies were
      retrospectively analyzed according to demographic- and injury variables which
      result in GCS and GOS. RESULTS: In univariate analysis, mode of injury showed a
      significant effect on combined injury (p<0.001), as were the cases with skull
      fracture on radiologic finding (p<0.000). The GCS showed a various correlation
      with radiologic finding (p<0.000), mode of injury (p<0.002), but less favorably
      with impact site (p<0.052), age (p<0.054) and skull fracture (p<0.057), in order
      of statistical significances. However, only GOS showed a definite correlation to
      radiologic finding (p<0.000). In multivariate analysis, the individual variables
      to enhance an unfavorable effect on GCS were radiologic finding [odds ratio (OR)
      7.327, 95% confidence interval (CI)], mode of injury (OR; 4.499, 95% CI) and age
      (OR; 3.141, 95% CI). Those which influence an unfavorable effect on GOS were
      radiologic finding (OR; 25.420, 95% CI) and age (OR; 2.674, 95% CI). CONCLUSION:
      In evaluation of TBSI on outcome, the variables such as radiological finding,
      mode of injury, and age were revealed as three important ones to have an
      unfavorable effect on early stage outcome expressed as GCS. However, mode of
      injury was shown not to have an unfavorable effect on late stage outcome as GOS.
      Among all unfavorable variables, radiological finding was confirmed as the only
      powerful prognostic variable both on GCS and GOS.

PMID- 22396840
TI  - Quantitative analysis of developmental process of cranial suture in korean
      infants.
AB  - OBJECTIVE: The purpose of this study was to elucidate the anatomical development
      of physiologic suture closure processes in infants using three dimensional
      reconstructed computed tomography (CT). METHODS: A consecutive series of 243
      infants under 12 months of age who underwent three dimensional CT were included
      in this study. Four major cranial sutures (sagittal, coronal, lambdoidal and
      metopic suture) were classified into four suture closure grades (grade 0=no
      closure along the whole length, grade 1=partial or intermittent closure, grade
      2=complete closure with visible suture line, grade 3=complete fusion
      (ossification) without visible suture line), and measured for its closure degree
      (suture closure rates; defined as percentage of the length of closed suture line
      divided by the total length of suture line). RESULTS: Suture closure grade under
      12 months of age comprised of grade 0 (n=195, 80.2%), grade 1 (n=24, 9.9%) and
      grade 2 (n=24, 9.9%) in sagittal sutures, whereas in metopic sutures they were
      grade 0 (n=61, 25.1%), grade 1 (n=167, 68.7%), grade 2 (n=6, 24%) and grade 3
      (n=9, 3.7%). Mean suture closure rates under 12 months of age was 58.8% in
      metopic sutures, followed by coronal (right : 43.8%, left : 41.1%), lambdoidal
      (right : 27.2%, left : 25.6%) and sagittal sutures (15.6%), respectively.
      CONCLUSION: These quantitative descriptions of cranial suture closure may help
      understand the process involved in the cranial development of Korean infants.

PMID- 22396841
TI  - Massive intracerebral hemorrhage caused by a cavernous malformation.
AB  - We present a rare case of massive intracerebral hemorrhage resulting from a
      small, superficially-located supratentorial cavernous malformation, or cavernoma.
      These lesions rarely lead to massive, life-threatening intracerebral hemorrhages.
      A 17-year-old female presented with a 3-week history of declining mental status.
      Brain computed tomography and magnetic resonance imaging revealed a sizable
      intracranial hemorrhage, within the right occipital region, associated with a
      small nodule at the hematoma's posterior margin. An emergency operation removed
      the entire hematoma and nodule. Histological examination of the nodule was
      compatible with a diagnosis of cavernous malformation. The patient's post
      operative course was uneventful.

PMID- 22396842
TI  - Dissecting aneurysm associated with a double origin of the posterior inferior
      cerebellar artery causing subarachnoid hemorrhage.
AB  - Two cases of the posterior fossa dissecting aneurysm associated with a double
      origin of the posterior inferior cerebellar artery (DOPICA) causing subarachnoid
      hemorrhage are presented. After observing a relationship between the aneurysm and
      DOPICA on a three dimensional rotational angiogram (3DRA), the dissecting
      aneurysms were successfully obliterated by surgical trapping and endovascular
      internal trapping, respectively. This report warrants suspecting DOPICA of an
      associating anomaly predisposing to dissecting aneurysm in the vertebral artery
      posterior inferior cerebellar artery territory and highlights the role of 3DRA in
      pretreatment evaluation of unusual aneurysms accompanying a particular anatomical
      variation.

PMID- 22396843
TI  - The unusual origin of the sternocleidomastoid artery from the lingual artery.
AB  - The sternocleidomastoid (SCM) artery supplying blood to the SCM muscle has
      different origins according to its anatomical segment. The authors performed
      cadaveric neck dissection to review the surgical anatomy of neurovascular
      structures surrounding the carotid artery in the neck. During the dissection, an
      unusual finding was cited in which the SCM artery supplying the middle part of
      the SCM muscle originated from the lingual artery (LA); it was also noted that it
      crossed over the hypoglossal nerve (HN). There have been extremely rare reports
      citing the SCM artery originated from the LA. Though the elevation of the HN over
      the internal carotid artery was relatively high, the vascular loop crossing over
      the HN was very close to the carotid bifurcation. Special anatomical
      consideration is required to avoid the injury of the HN during carotid artery
      surgery.

PMID- 22396844
TI  - Rapid clinical course of cerebral metastatic angiosarcoma from the heart.
AB  - We report here one case of rapid and aggressive course of cerebral metastatic
      angiosarcoma from the heart. A 36-year-old man presented with 10-days history of
      headache. Magnetic resonance imaging demonstrated subacute hemorrhage with a
      small region of enhancement in right parietal region and the pathological
      diagnosis was angiosarcoma. Transthoracic echocardiography demonstrated 3.2*3 cm
      sized mass on right atrial wall. Newly developed lesion was reoperated, three and
      four weeks later respectively, and whole brain radiotherapy of total 30 Gy was
      done. With the interval of two months, gamma knife surgery was done for new
      lesions two times, which were well controlled. Newly developed lesions rapidly
      happened even in the adjuvant treatment. He died 9 months after the diagnosis
      because of the aggravation of primary cancer. The cerebral metastatic
      angiosarcoma from the heart showed the rapid aggressive behavior and the closed
      follow-up could be needed for the adjuvant treatment.

PMID- 22396845
TI  - Femoral Neuropathy due to Iliacus Muscle Hematoma in a Patient on Warfarin
      Therapy.
AB  - Spontaneous hematomas of the iliacus muscle are rare lesions and these are seen
      in individuals receiving anticoagulation therapy or patients with blood
      dyscrasias such as hemophilia. It can cause femoral neuropathy and resultant pain
      and paralysis. Although there is no clear consensus for the treatment of femoral
      neuropathy from iliacus muscle hematomas, delays in the surgical evacuation of
      hematoma for decompression of the femoral nerve can lead to a prolonged or
      permanent disability. We report here on a rare case of a spontaneous iliacus
      muscle hematoma that caused femoral neuropathy in a patient who was taking
      warfarin for occlusive vascular disease and we discuss the treatment.

PMID- 22396846
TI  - Solitary xanthogranuloma of the upper cervical spine in a male adult.
AB  - We present the rare case of solitary xanthogranuloma in the upper cervical column
      mimicking a Brown-Sequard syndrome. A 29-year-old man complained with right
      hemiparesis and left hypoesthesia after a car accident. Computed tomography and
      magnetic resonance images revealed a lobulated homogenously well-enhancing mass
      in between posterior arch of the atlas (C1) and spinous process of the axis (C2)
      resulting in a marked spinal canal narrowing with cortical erosions. The patient
      was managed by complete resection of the tumor with partial laminectomy with
      lower half of C1 posterior arch and upper half of C2 spinous process. The authors
      advise complete removal of the xanthogranuloma and consideration as a
      differential diagnosis of lesions among upper cervical lesions.

PMID- 22396847
TI  - Hemifacial spasm developed after contralateral vertebral artery ligation.
AB  - Although the mechanism of hemifacial spasm (HFS) is not yet well established,
      vascular compression of the facial nerve root exit zone and hyperexcitability of
      the facial nucleus have been suggested. We report a case of HFS in the setting of
      coinciding intracranial hemorrhage (ICH) of the pons and proximal ligation of the
      contralateral vertebral artery (VA) for the treatment of a fusiform aneurysm of
      the distal VA and discuss the possible etiologies of HFS in this patient. A 51
      year-old male with an ICH of the pons was admitted to our hospital. Neuroimaging
      studies revealed an incidental fusiform aneurysm of the right VA distal to the
      origin of the posterior inferior cerebellar artery. Eight months after proximal
      ligation of the VA the patient presented with intermittent spasm of the left side
      of his face. Pre- and post-ligation magnetic resonance angiography revealed an
      enlarged diameter of the VA. The spasm completely disappeared after microvascular
      decompression.

PMID- 22396848
TI  - Endovascular treatment of a large partially thrombosed basilar tip aneurysm.
AB  - Despite the remarkable developments in neurosurgical and neuro-interventional
      procedures, the optimal treatment for large or giant partially thrombosed
      aneurysms with a mass effect remains controversial. The authors report a case of
      a partially thrombosed aneurysm with a mass effect, which was successfully
      treated by stent-assisted coil embolization. A 41-year-old man presented with
      headache. Brain computed tomography depicted an 18*18 mm sized thrombosed
      aneurysm in the interpeducular cistern. More than 80% of the aneurysm volume was
      filled with thrombus and the canalized portion beyond its neck measured 6.8*5.6
      mm by diagnostic cerebral angiography. Stent-assisted endovascular coiling was
      performed on the canalized sac and the aneurysm was completely obliterated.
      Furthermore, most of the thrombosed aneurysm disappeared in the interpeduncular
      cistern was clearly visualized follow-up brain magnetic resonance imaging
      conducted at 21 months. The authors report a case of selective coiling of a
      large, partially thrombosed basilar tip aneurysm.

PMID- 22396849
TI  - Free Hand Pedicle Screw Placement in the Thoracic Spine without Any Radiographic
      Guidance : Technical Note, a Cadaveric Study.
AB  - Thoracic pedicle screw fixation techniques are still controversial for thoracic
      deformities because of possible complications including neurologic deficit.
      Methods to aid the surgeon in appropriate screw placement have included the use
      of intraoperative fluoroscopy and/or radiography as well as image-guided
      techniques. We describe our technique for free hand pedicle screw placement in
      the thoracic spine without any radiographic guidance and present the results of
      pedicle screw placement analyzed by computed tomographic scan in two human
      cadavers. This free hand technique of thoracic pedicle screw placement performed
      in a step-wise, consistent, and compulsive manner is an accurate, reliable, and
      safe method of insertion to treat a variety of spinal disorders, including spinal
      deformity.

PMID- 22396850
TI  - Neoplastic meningitis resulting from hematological malignancies: pharmacokinetic
      considerations and maximizing outcome.
AB  - Neoplastic meningitis, also known as leptomeningeal metastases, is a complication
      of various types of cancer that occurs when tumor cells enter the cerebrospinal
      fluid (CSF), travel along CSF pathways and grow. Treatment options include drug
      delivery directly into the CNS or systemic administration for targeted action in
      the CNS. CNS drug delivery is limited by the blood-brain barrier and the blood
      CSF barrier. It may be possible to partially overcome this by using high-dose
      systemic therapy; however, this is done at the possible expense of increased
      systemic toxicity. Intra-CSF drug delivery bypasses the blood-brain barrier and
      allows direct access of the chemotherapeutic agent to the CSF. Because neoplastic
      meningitis occurs in an increasingly large percentage of all cancer patients, it
      is imperative to optimize drug delivery to the CSF and meninges. Both the
      pharmacokinetic profile of the chemotherapeutic agent and the site of
      administration influence therapeutic efficacy. Achieving prolonged therapeutic
      cytotoxic drug concentrations and even distribution in the CSF will improve
      efficacy. In this article we summarize data on the efficacy, safety and outcome
      of high-dose systemic and intra-CSF treatments.

PMID- 22396852
TI  - Fast by nature - how stress patterns define human experience and performance in
      dexterous tasks.
AB  - In the present study we quantify stress by measuring transient perspiratory
      responses on the perinasal area through thermal imaging. These responses prove to
      be sympathetically driven and hence, a likely indicator of stress processes in
      the brain. Armed with the unobtrusive measurement methodology we developed, we
      were able to monitor stress responses in the context of surgical training, the
      quintessence of human dexterity. We show that in dexterous tasking under critical
      conditions, novices attempt to perform a task's step equally fast with
      experienced individuals. We further show that while fast behavior in experienced
      individuals is afforded by skill, fast behavior in novices is likely instigated
      by high stress levels, at the expense of accuracy. Humans avoid adjusting speed
      to skill and rather grow their skill to a predetermined speed level, likely
      defined by neurophysiological latency.

PMID- 22396851
TI  - Self-circularizing 5'-ETS RNAs accumulate along with unprocessed pre ribosomal
      RNAs in growth-stressed Entamoeba histolytica.
AB  - The primary transcript of rRNA genes is a large pre rRNA which is precisely
      processed to release the mature rRNAs. The 5'-external transcribed spacer (ETS)
      of rRNA genes contains important sites for pre rRNA processing. Once the
      processing is accomplished the ETS is rapidly degraded. We show that in growth
      stressed cells of the human parasitic protist Entamoeba histolytica the A'-A(0)
      sub-fragment of the 5'-ETS accumulates to high levels as a family of RNA
      molecules of size 666 to 912 nt. These etsRNAs are circular in vivo and can
      spontaneously self-circularize in vitro. The accumulation of etsRNAs is
      accompanied by accumulation of unprocessed pre rRNA, indicating a possible role
      of etsRNAs in inhibition of processing during growth stress. Our data shows for
      the first time that processed etsRNA is not a mere by-product destined for
      degradation but is stabilized by circularization and could play a regulatory role
      as noncoding RNA.

PMID- 22396853
TI  - A&D, a bridge between aging and age-related disease.

PMID- 22396855
TI  - Memory and neurogenesis in aging and Alzheimer's disease.
AB  - A possible link between a deficient neurogenesis at the dentate gyrus, and the
      loss of memory found in Alzheimer's disease patients is discussed. First is
      indicated that Alzheimer disease is a memory disorder. Since adult neurogenesis
      at the dentate gyrus plays a role in declarative memory, a brief comment on the
      structure and function of dentate gyrus has been included. At molecular level, we
      have discussed the function of the enzyme GSK3 on the development of neurogenesis
      at the subgranular zone of the dentate gyrus. Finally, we have indicated that in
      Alzheimer disease there is an increase in GSK3 activity. This increase could
      impair the neurogenesis process and it could result in the memory deficit found
      in Alzheimer patients.

PMID- 22396854
TI  - Reelin-mediated Signaling during Normal and Pathological Forms of Aging.
AB  - Reelin is a large extracellular matrix protein essential for mediating proper
      neuronal positioning during development. Employing the same lipoprotein-mediated
      signaling cascade, Reelin regulates NMDA receptor homeostasis and modulates
      synaptic function and plasticity in adult synapses. In line, aging-related
      reduction in Reelin expression has been shown to contribute to cognitive
      impairments during normal aging. Although recent experimental evidence suggests
      an involvement of dysfunctional Reelin in pathological forms of aging, such as
      late-onset Alzheimer's disease (AD), the molecular mechanisms by which this
      conserved extracellular glycoprotein contributes to the pathogenesis of AD
      remains still largely unknown. In the present review, we briefly summarize the
      role of Reelin in the developing and adult brain and discuss the implication of
      loss- or gain-of-functions of developmental programs in the adult brain as
      putative inducing factors of pathological forms of aging. Finally, we will
      propose some new concepts on the role of inflammatory cytokines in interfering
      with Reelin-mediated signaling during neurodevelopment and adult synaptic
      function, and discuss how this could be translated into a novel non-transgenic
      mouse model of late-onset AD. Thus, the findings presented in this review are
      aimed to highlight the important role of Reelin-mediated signaling in maintaining
      a crucial developmental program in the adult brain that is required to prevent
      the shift from normal to pathological aging.

PMID- 22396857
TI  - Stem cell transplantation for enhancement of learning and memory in adult
      neurocognitive disorders.
AB  - The role of adult hippocampal neurogenesis in learning and memory is still
      incompletely understood. Ablation of neurogenesis with different methods produced
      equivocal results with respect to working memory in Morris water maze and radial
      arm maze experiments. Therefore, it is remarkable that in the past few years
      several investigators have found a positive impact on working memory after adding
      stem or progenitor cells to the hippocampus in various disease models. The
      literature on stem cell transplantation for adult neurocognitive disorders is
      reviewed in this article and attempted to be reconciled with current research on
      adult hippocampal neurogenesis.

PMID- 22396856
TI  - Alzheimer's Disease: Fatty Acids We Eat may be Linked to a Specific Protection
      via Low-dose Aspirin.
AB  - It has been suggested that cognitive decline in aging is the consequence of a
      growing vulnerability to an asymptomatic state of neuroinflammation. Moreover, it
      is becoming more evident that inflammation occurs in the brain of Alzheimer's
      disease (AD) patients and that the classical mediators of inflammation,
      eicosanoids and cytokines, may contribute to the neurodegeneration. In agreement
      with this observation, aspirin (ASA) - a non-steroidal anti-inflammatory drug -
      may protect against AD and/or vascular dementia. However, both the time of
      prescription and the dose of ASA may be critical. A major indication for low-dose
      ASA is in combination with docosahexaenoic acid (DHA). DHA plays an essential
      role in neural function and its anti-inflammatory properties are associated with
      the well-known ability of this fatty acid to inhibit the production of various
      pro-inflammatory mediators, including eicosanoids and cytokines. Higher DHA
      intake is inversely correlated with relative risk of AD and DHA+ASA supplement
      may further decrease cognitive decline in healthy elderly adults. Although low
      dose ASA may be insufficient for any anti-inflammatory action the concomitant
      presence of DHA favours a neuroprotective role for ASA. This depends on the
      allosteric effects of ASA on cyclooxygenase-2 and following production - from DHA
      - of specific lipid mediators (resolvins, protectins, and electrophilic oxo
      derivatives). ASA and DHA might protect against AD, although controlled trials
      are warranted.

PMID- 22396858
TI  - Signaling and Damaging Functions of Free Radicals in Aging-Free Radical Theory,
      Hormesis, and TOR.
AB  - Harman's Free Radical Theory of Aging has been considered as a major theory of
      aging for more than 50 years. In 1956 Dr. Harman proposed that the accumulation
      of free radicals with the age causes the damage of biomolecules by these reactive
      species and the development of pathological disorders resulting in cell
      senescence and organismal aging. His hypothesis was supported by numerous
      experimental studies demonstrated an increase in free radical levels in cells and
      living organisms with aging. In subsequent years important discoveries of new
      physiological free radicals superoxide and nitric oxide have been made that led
      to understanding of other important functions of free radicals. It has been shown
      that superoxide and nitric oxide together with their diamagnetic reaction
      products hydrogen peroxide and peroxynitrite (all are now named reactive oxygen
      and nitrogen species, ROS and RNS) function as signaling species in many
      physiological enzymatic/gene processes. Furthermore, the disturbance of ROS and
      RNS physiological signaling can be an origin of various pathologies and aging.
      These discoveries demanded to widen original free radical theory of aging and to
      consider the damaging ROS signaling as an important, maybe major route to cell
      senescence and organismal aging. However, some experimental findings such as the
      extension of lifespan by calorie restriction of yeast, flies, worms, and mice,
      and favorable effects of physical exercises stimulated criticism of free radical
      theory because the expansion of lifespan accompanied in some cases by increasing
      oxidative stress. On these grounds such theories as Hormesis and Target of
      rapamycin (mTOR) theories refute the role of ROS and oxidative stress in aging.
      Accordingly, a major purpose of this review to show that ROS signaling is
      probably the most important enzyme/gene pathway responsible for the development
      of cell senescence and organismal aging and that ROS signaling might be
      considered as further development of free radical theory of aging. In spite of
      apparent contradictions the Hormesis or TOR theories are also describing
      processes of aging development regulated by ROS signaling.

PMID- 22396859
TI  - Dietary restriction and aging in rodents: a current view on its molecular
      mechanisms.
AB  - Dietary restriction (DR) is a robust non-genetic intervention that reduces
      morbidity and mortality in a range of organisms. This suggests the presence of an
      evolutionary-conserved pathway that regulates aging and lifespan in response to
      reduced food or energy intake. Recent genetic analyses have shown that single
      gene mutations could extend the lifespan, even in mammals. Many longevity genes
      are clustered into nutrient-sensing and metabolic adaptation pathways, which are
      also thought to be involved in the effect of DR. The responses of these mutant
      animals to DR in terms of lifespan or other aging phenotypes suggest that
      proteins encoded by these genes are involved in the effects of DR. This review
      focuses on the roles of fork head box O (FoxO) transcription factors, AMP
      activated protein kinase (AMPK), and sirtuins (particularly SIRT1) in the effects
      of DR in rodents. FoxO transcription factors are mammalian orthologs of DAF-16,
      which is required for the lifespan extending effects of reduced insulin-like
      signaling in nematodes. A recent study in rodents suggested that FoxO1 is
      involved in the anti-neoplastic effects of DR. Although aak2 in nematodes
      (mammalian AMPK), Sir2 in yeast and Sir2.1 in nematodes (mammalian SIRT1) were
      also reported to be essential for lifespan extension by DR, the findings are
      thought to depend on the genetic backgrounds of the organisms and/or methods used
      to induce DR. In rodents, AMPK and SIRT1 are implicated in the metabolic
      regulation by long-term DR. Genetic and molecular dissection of the mechanisms
      underlying the effects of DR will provide us with knowledge of the basic aging
      processes, as well as insights into the development of DR mimetics, to extend the
      healthy lifespan in humans.

PMID- 22396861
TI  - Old age as a privilege of the "selfish ones".
AB  - In the past couple of centuries, scientists proposed great number of aging
      theories but neither of them appears to be fully satisfactory. In the statistical
      sense, we are dealing with an even greater challenge because large array of
      factors affects the aging process. Although at this point the most of these
      factors are well known, it is the very fact of their innumerability that
      complicates approaches to the issue at hand. Both in life and in medicine, the
      cause behind an effect can rarely be unequivocally determined. Thus, it appears
      that through out human history longevity has been primarily affected by
      eradication of diseases, especially by eradication of infectious diseases and
      introduction of the vaccines. For that reason, maybe we should not be referring
      to this issue as the "fountain of youth" but rather as the "vaccine of youth".
      The postulate that genetic instability is the precipitating factor both of aging
      and cancer has withstood many tests and keeps on being reaffirmed. For this
      reason, it is legitimate to pose a question of whether long-lived individuals may
      be those with "selfish" genes and more stable genetic material. They certainly
      cannot avoid aging, but aging in such individuals could be delayed due to steady
      character of their genome, which is less susceptible to mutations. On the
      population level, they constitute minority because stable genome would represent
      an obstacle to successful evolution of the species. If this was not the case, we
      might not be writing all these texts today.

PMID- 22396862
TI  - Insulin, IGF-1 and longevity.
AB  - It has been demonstrated in invertebrate species that the evolutionarily
      conserved insulin and insulin-like growth factor (IGF) signaling (IIS) pathway
      plays a major role in the control of longevity. In the roundworm Caenorhabditis
      elegans, single mutations that diminish insulin/IGF-1 signaling can increase
      lifespan more than twofold and cause the animal to remain active and youthful
      much longer than normal. Likewise, substantial increases in lifespan are
      associated with mutations that reduce insulin/IGF-1 signaling in the fruit fly
      Drosophila melanogaster. In invertebrates, multiple insulin-like ligands exist
      that bind to a common single insulin/IGF-1 like receptor. In contrast, in
      mammals, different receptors exist that bind insulin, IGF-1 and IGF-2 with
      different affinities. In several mouse models, mutations that are associated with
      decreased GH/IGF-1 signaling or decreased insulin signaling have been associated
      with enhanced lifespan. However, the increased complexity of the mammalian
      insulin/IGF-1 system has made it difficult to separate the roles of insulin, GH
      and IGF-1 in mammalian longevity. Likewise, the relevance of reduced insulin and
      IGF-1 signaling in human longevity remains controversial. However, studies on the
      genetic and metabolic characteristics that are associated with healthy longevity
      and old age survival suggest that the conserved ancient IIS pathway may also play
      a role in human longevity.

PMID- 22396863
TI  - Aging and neurogenesis, a lesion from Alzheimer's disease.
AB  - The evidence that neurogenesis occurs in the adult brain and neural stem cells
      (NSCs) reside in the adult central nervous system (CNS) of mammals opens new
      avenues and opportunities for our understanding of development and for therapy.
      Newly generated neuronal cells of the adult brain would contribute to the physio
      pathology of the nervous system and the adult brain may be amenable to repair.
      The contribution of adult neurogenesis to the functioning of the nervous system
      remains to be elucidated and adult NSCs have yet to be brought to therapy. It is
      generally accepted that NSCs in the adult brain have a regenerative capacity.
      Yet, evidences suggest that they may also contribute to pathological developments
      in neurological diseases. Alzheimer's disease (AD) is a neurodegenerative disease
      and the hippocampus is one of the regions of the brain the most affected by the
      disease. AD is characterized by neurodegeneration, amyloid plaques,
      neurofibrillary tangles, aneuploidy and enhanced neurogenesis in the adult brain.
      The process of adult neurogenesis holds the potential to generate populations of
      cells that are aneuploid, particularly in the neurogenic regions. Aneuploid newly
      generated neuronal cells of the adult brain would contribute to the pathology of
      AD. Adult neurogenesis would not only contribute to regenerative attempts in the
      CNS, but also to the pathogenesis of neurological diseases and disorders.

PMID- 22396860
TI  - Aging and the Mammalian regulatory triumvirate.
AB  - A temporal framework linking circadian rhythms and clocks to aging rates
      identifies a specific window of target of rapamycin (TOR) signaling associated
      with growth hormone (GH) and insulin-like growth factor (IGF-1) (largely
      exclusive of insulin) in early sleep. IGF-1 signaling is released by growth
      hormone secretory peaks and downregulation of IGF-1 binding protein-1 resulting
      in activation of the mitogen activated protein kinase/extracellular signal
      response kinase (MAPK/ERK) and phosphoinositide 3-kinase-protein kinase B (PI3K
      PKB/Akt) signaling pathways. Phosphorylation of Akt activates TOR which mediates
      the protein synthesis and growth functions of the GH axis. TOR activity is also
      associated with downregulated stress resistance, faster aging and reduced
      lifespan. IGF-1 signaling is terminated by falling GH and upregulation of IGF-1
      binding proteins mediated by somatostatin and rising corticosteroids in later
      sleep. This suppresses PI3K-Akt signaling, thus activating the forkhead
      transcription factors (FOXOs) and stress-resistance pathways involved in
      promoting longevity. Thus, sleep appears to encompass both pathways currently
      identified as most relevant to aging and they toggle successively on the
      phosphorylation status of Akt. I propose a modified version of Pearl's rate of
      living theory emphasizing the hard-wired antagonism of growth (TOR) and stress
      resistance (FOXO). The sleep association of TOR and FOXO in temporally separated
      windows and their sequential temporal deployment may change much of the way we
      think about aging and how to manipulate it.

PMID- 22396864
TI  - Neuroimmunomodulation by calcineurin in aging and Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive, age-related neurodegenerative disorder
      which first manifests as profound memory dysfunction. The majority of cases are
      idiopathic, although advanced age is the greatest risk factor for AD. Recent
      evidence suggests that pre-fibrillar soluble amyloid-beta (Abeta) underlies an
      early, progressive loss of synapses that is a hallmark of AD. One of the
      downstream effects mediated by soluble Abeta aggregates is the hyperactivation of
      the phosphatase calcineurin (CaN). This important phosphatase is abundant in the
      nervous system and intimately involved in the mechanisms of memory as well as the
      immune response. Such a duality places CaN at the crux of neuroimmunomodulation
      processes. In the present review, we briefly summarize the role of CaN in
      physiological aging and discuss how CaN hyperactivity could cause the memory
      impairment, neuroinflammation, and neuronal death that are pathological
      mechanisms of AD.

PMID- 22396865
TI  - The impact of glial activation in the aging brain.
AB  - The past decade or so has witnessed a rekindling of interest in glia requiring a
      re-evaluation of the early descriptions of astrocytes as merely support cells,
      and microglia as adopting either a resting state or an activated state in a
      binary fashion. We now know that both cell types contribute to the optimal
      functioning of neurons in the healthy brain, and that altered function of either
      cell impacts on neuronal function and consequently cognitive function. The
      evidence indicates that both astrocytic and microglial phenotype change with age
      and that the shift from the resting state is associated with deterioration in
      synaptic function. In this review, we consider the rapidly-expanding array of
      functions attributed to these cells and focus on evaluating the changes in cell
      activation that accompany ageing.

PMID- 22396866
TI  - Aging of the subventricular zone neural stem cell niche.
AB  - The persistence of an active subventricular zone neural stem cell niche in the
      adult mammalian forebrain supports its continued role in the production of new
      neurons and in generating cells to function in repair through adulthood.
      Unfortunately, with increasing age the niche begins to deteriorate, compromising
      these functions. The reasons for this decline are not clear. Studies are
      beginning to define the molecular and physiologic changes in the microenvironment
      of the aging subventricular zone niche. New revelations from aging studies will
      allow for a more thorough understanding of which reparative functions are lost in
      the aged brain, the progression of niche demise and the possibility for
      therauptic intervention to improve aging brain function.

PMID- 22396867
TI  - Brain Aging and Regeneration after Injuries: an Organismal approach.
AB  - Aging is associated with a decline of locomotor, sensory and cognitive
      performance in humans and experimental animals. The rate and pattern of
      organismal senescence may be regulated in part by changes in multiple genes
      involved in multiple processes. While this theory is supported by genetic data in
      lower organisms, a lack of direct experimental evidence in higher organisms has
      contributed to a broader acceptance of the "stochastic aging" model, in which
      accumulating, random damaging biological events play an important role. However,
      these insults alone cannot account for the inexorable deterioration and loss of
      function that characterizes aging. The higher the complexity of a system, the
      less obvious is the effect of genetic regulation on aging and the life span,
      indicating that epigenetic factors play an important role in aging. Most
      importantly, we present evidence that aging systems do retain some capacity for
      regeneration and functional recovery after injuries to the central nervous system
      like cerebral ischemia.

PMID- 22396869
TI  - Nitroproteins Identified in Human Ex-smoker Bronchoalveolar Lavage Fluid.
AB  - The long-term goal of our study is to identify chronic obstructive pulmonary
      disease (COPD)-related bronchoalveolar lavage fluid (BALF) nitroproteins to
      clarify COPD pathological mechanisms and to discover biomarkers of COPD. The goal
      of the present study was to detect the presence of, and potential roles of,
      nitroproteins in, human ex-smoker (without COPD) BALF samples. Nitroproteins were
      immunoprecipitated from two separate BALF samples, and digested with trypsin; and
      tryptic peptides were analyzed with matrix-assisted laser desorption/ionization
      (MALDI)-tandem mass spectrometry (MS/MS). Each MS/MS spectrum was composed of
      accumulated scans (n = 50-100). The MS/MS data were searched with BioWorks 2.0
      TuboSequest in the SwissProt database to generate the amino acid sequence, which
      was evaluated manually. Eleven nitrotyrosine sites were identified in eight
      proteins, including progestin and adipoQ receptor family member III, zinc finger
      protein 432, proteasome subunit alpha type 2, NADH-ubiquinone oxidoreductase B14,
      slit homolog 1 protein, lysozyme, aldose 1-epimerase, and PTS system lactose
      specific EIICB component. Each nitrotyrosine site was located within a specific
      protein domain and motif. Those identified nitrated proteins could be involved in
      multiple functional metabolic systems, including transcriptional regulation,
      mitochondrial complex, immune system, and energy metabolism.

PMID- 22396868
TI  - Aging and stress: past hypotheses, present approaches and perspectives.
AB  - Brain aging has been suggested to be conditioned by an excessive glucocortioid
      secretion leading to damages on brain areas involved not only in cognitive and
      emotional processes but also in the control of the activity of the hypothalamic
      pituitary adrenal axis. This review describes some of the hypothesis that try to
      explain the relation between the dysregulation of the stress response and brain
      aging, focusing on corticosterone but also on neurotransmission in the
      hippocampus, the prefrontal cortex and the amygdala. Moreover, different
      molecular factors can account for an enhanced vulnerability of the aged brain to
      stress exposure, specially for resilience. Among them, good candidates could be
      those mechanisms determining the levels of corticosterone in the brain, several
      molecules downstream glucocorticoid receptor activation (ie: heat shock proteins,
      BAG-1) or even the epigenetic programming of the HPA axis in early stages. In
      conclusion, genetic and environmental factors (early life stress, chronic stress
      during adulthood) can produce an enhanced vulnerability and a reduced resilience
      of the brain to subsequent stress exposures or to metabolic challenges leading,
      in turn, to an unsuccessful aging of the brain. However, results obtained with
      the use of the environmental enrichment model in animals, added to several
      results in humans also described in this review suggest that positive
      environmental factors (cognitive-demanding tasks or physical exercise) can help
      to maintain neuronal plasticity during aging and to protect the brain against the
      damaging effects of stress exposure.

PMID- 22396871
TI  - Ischemic preconditioning in the younger and aged heart.
AB  - Ischemic preconditioning is the effect of brief ischemic episodes which protect
      the heart from the following more prolonged ischemic episode. This mechanism is
      effective in younger but not in aged heart. The age-related reduction of ischemic
      preconditioning has been demonstrated in experimental models and in elderly
      patients. Preinfarction angina, a clinical equivalent of ischemic
      preconditioning, reduces mortality in adult but not in elderly patients with
      acute myocardial infarction. Physical activity or caloric restriction is
      partially capable to preserve the cardioprotective effect of ischemic
      preconditioning in the aging heart. More importantly, physical activity and
      caloric restriction in tandem action completely preserve the protective mechanism
      of ischemic preconditioning. Accordingly, the protective mechanism of
      preinfarction angina is preserved in elderly patients with a high grade of
      physical activity or a low body-mass index. Thus, both physical activity and
      caloric restriction are confirmed as powerful anti-aging interventions capable to
      restore age-dependent reduction of a critical endogenous protective mechanism
      such as ischemic preconditioning.

PMID- 22396872
TI  - Aging and transplantation - a topic for biomedicine or bioethics?
AB  - The aged patient stands at the nexus of significant biomedical and bioethical
      issues in transplantation. This in itself can be seen as a microcosm of an
      imminent global tempest, stemming from expanding numbers and longer lives of the
      aged population. As a candidate for receiving organ and tissue transplants, the
      geriatric patient is challenging because they present unique physiology for
      medical management. As organ and tissue donors, the aged are perceived of as
      providing "marginal" organs, which drives the fear that the graft will fail
      before the recipient. Such difficulties lead inexorably to several unique
      bioethical considerations for transplantation with this population. The thorny
      conundrums for society hinge on fairness versus discrimination based on age,
      played out under the enormous and probably intractable problem of severe donor
      organ shortages. Fortunately, recent findings offer some rather unexpected new
      and favorable prospects. Notably, aged donors can provide organs with good,
      lifesaving function, even though there are nonetheless age-related compromises
      present. On the other side of the coin, there is less doubt that recipients can
      have their lives extended with high quality through transplantation. Here they
      benefit from some (counterintuitively) positive attributes for aging, such as
      reduced immune function, making immunosuppression less rigorous. Finally, the
      pressure of organ and tissue shortages plus the lifting of bans on embryonic stem
      cell research have portents for an explosive alternative to transplantation of
      adult organs. Stem cells also lend credibility to prospects for realizing
      regenerative medicine, assuming ethical and religious concerns can be satisfied.

PMID- 22396870
TI  - Myocardial infarction in the elderly.
AB  - Advances in pharmacological treatment and effective early myocardial
      revascularization have -in recent years- led to improved clinical outcomes in
      patients with acute myocardial infarction (AMI). However, it has been suggested
      that compared to younger subjects, elderly AMI patients are less likely to
      receive evidence-based treatment, including myocardial revascularization therapy.
      Several reasons have been postulated to explain this trend, including uncertainty
      regarding the true benefits of the interventions commonly used in this setting as
      well as increased risk mainly associated with comorbidities. The diagnosis,
      management, and post-hospitalization care of elderly patients presenting with an
      acute coronary syndrome pose many difficulties at present. A complex interplay of
      variables such as comorbidities, functional and socioeconomic status, side
      effects associated with multiple drug administration, and individual biologic
      variability, all contribute to creating a complex clinical scenario. In this
      complex setting, clinicians are often required to extrapolate evidence-based
      results obtained in cardiovascular trials from which older patients are often,
      implicitly or explicitly, excluded. This article reviews current recommendations
      regarding management of AMI in the elderly.

PMID- 22396873
TI  - Aging genetics and aging.
AB  - The process of aging refers to the decay of an organism's structure and function,
      in which molecular and cellular modifications can have various effects at the
      individual level over the course of a lifetime. The accumulation of molecular
      errors that compromise adult stem cell functions occurs because of genetic and
      epigenetic interactions and depends on hereditary, environmental, and stochastic
      factors. Here we review the known genetic factors involved in aging.

PMID- 22396874
TI  - Reactive oxygen species signaling in cancer: comparison with aging.
AB  - This work considers reactive oxygen species (ROS) signaling in solid tumors. Most
      (probably all) cancer cells are characterized by ROS overproduction that is they
      exist under conditions of incessant oxidative stress. For example ROS
      overproduction has been shown in prostate, pancreatic, melanoma, and glioma
      cells. ROS overproduction has been also demonstrated in breast, liver, bladder,
      colon, and ovarian cancers. Although these examples probably do not incorporate
      all the described data concerning ROS overproduction in cancer cells, they
      clearly support a proposal about enhanced oxidative stress in these cells.
      Therefore the mechanisms of ROS signaling in the survival and death of cancer
      cells and comparison with ROS signaling in senescent cells ought to be
      considered. It might be suggested that ROS overproduction in cancer cells is a
      major origin of their survival and resistance to anticancer treatment while the
      enhanced oxidative stress responsible for aging development. However it is of
      particular interest that additional ROS production by prooxidants can induce
      apoptosis in cancer cells. We suggest that moderate oxidative stress can
      stimulate proliferation and survival of cancer sells by conditioning mechanism
      while the enhancement of ROS overproduction by prooxidants under severe oxidative
      stress results in apoptosis and cell death. Aging development is always
      characterized by harmful ROS overproduction although the moderate increase in ROS
      formation in senescent cells might be not dangerous. Similar double-edged sword
      effects of ROS might be observed during the development of other pathologies for
      example diabetes mellitus.

PMID- 22396875
TI  - Why do hair cells and spiral ganglion neurons in the cochlea die during aging?
AB  - Age-related decline of cochlear function is mainly due to the loss of hair cells
      and spiral ganglion neurons (SGNs). Recent findings clearly indicate that
      survival of these two cell types during aging depends on genetic and
      environmental interactions, and this relationship is seen at the systemic,
      tissue, cellular, and molecular levels. At cellular and molecular levels, age
      related loss of hair cells and SGNs can occur independently, suggesting distinct
      mechanisms for the death of each during aging. This mechanistic independence is
      also observed in the loss of medial olivocochlear efferent innervation and outer
      hair cells during aging, pointing to a universal independent cellular mechanism
      for age-related neuronal death in the peripheral auditory system. While several
      molecular signaling pathways are implicated in the age-related loss of hair cells
      and SGNs, studies with the ability to locally modify gene expression in these
      cell types are needed to address whether these signaling pathways have direct
      effects on hair cells and SGNs during aging. Finally, the issue of whether age
      related loss of these cells occurs via typical apoptotic pathways requires
      further examination. As new studies in the field of aging reshape the framework
      for exploring these underpinnings, understanding of the loss of hair cells and
      SGNs associated with age and the interventions that can treat and prevent these
      changes will result in dramatic benefits for an aging population.

PMID- 22396878
TI  - From bench to bedside: unique challenges of treating epilepsy in the aging brain.

PMID- 22396876
TI  - Mitochondrial Dysfunction during Brain Aging: Role of Oxidative Stress and
      Modulation by Antioxidant Supplementation.
AB  - Mitochondrial dysfunction and oxidative stress are two interdependent and
      reinforcing damage mechanisms that play a central role in brain aging. Oxidative
      stress initiated and propagated by active oxyradicals and various other free
      radicals in the presence of catalytic metal ions not only can damage the
      phospholipid, protein and DNA molecules within the cell but can also modulate
      cell signalling pathways and gene expression pattern and all these processes may
      be of critical importance in the aging of brain. The present article describes
      the mechanism of formation of reactive oxyradicals within mitochondria and then
      explains how these can initiate mitochondrial biogenesis program and activate
      various transcriptional factors in the cytosol to boost up the antioxidative
      capacity of the mitochondria and the cell. However, a high level of oxidative
      stress finally inflicts critical damage to the oxidative phosphorylation
      machinery and mitochondrial DNA (mtDNA). The latter part of the article is a
      catalogue showing the accumulating evidence in favour of oxidative inactivation
      of mitochondrial functions in aged brain and the detailed reports of various
      studies with antioxidant supplementation claiming variable success in preventing
      the age-related brain mitochondrial decay and cognitive decline. The antioxidant
      supplementation approach may be of potential help in the management of
      neurodegenerative diseases like Alzheimer's disease. The newly developed
      mitochondria-targeted antioxidants have brought a new direction to experimental
      studies related to oxidative damage and they may provide potential drugs in near
      future for a variety of diseases or degenerative conditions including brain aging
      and neurodegenerative disorders.

PMID- 22396879
TI  - Pathophysiological considerations of seizures, epilepsy, and status epilepticus
      in the elderly.
AB  - Acute seizures, epilepsy and status epilepticus have the highest incidences in
      those over the age of 60 as compared to all other age groups. The most common
      etiological factors for epilepsy in the elderly are related to cerebrovascular
      disease. Diagnosing epilepsy in the elderly is challenging because of the subtle
      manifestations of partial seizures and the presence of age related cognitive
      difficulties, co-morbid conditions, and medications. Epilepsy treatment in this
      population is also difficult due to age related changes in pharmacokinetics and
      pharmacodynamics as well as individual variability. There are considerable gaps
      of knowledge about the basic pathophysiological mechanisms of recurrent partial
      onset seizures in the aged brain. This article critically reviews
      pathophysiological considerations that might impact the scientific approach of
      experimental research modeling of unprovoked seizures and epilepsy in elderly
      individuals, and the limited experimental epilepsy research on aged models.

PMID- 22396880
TI  - Seizure-induced Increased Neurogenesis Occurs in the Dentate Gyrus of Aged
      Sprague-Dawley Rats.
AB  - Neurogenesis in the hippocampal dentate gyrus persists throughout the lifespan of
      mammals, however, the rate of neurogenesis decreases as the animal ages. Although
      seizures increase neurogenesis in young adult brains, this relationship has not
      been shown in aged animals. Using doublecortin (DCX) immunocytochemistry, the
      number of DCX-labeled cells in the dentate gyrus from aged rats (23 months of
      age) was assessed 30 days following pilocarpine-induced seizures and was compared
      to the number obtained from age-matched control rats. DCX-labeled cells were
      located in the subgranular zone, at the border between the hilus and the granule
      cell layer, and within the granule cell layer in both epileptic and control aged
      brains. When comparing the aged epileptic rats to age-matched controls, there was
      a significant increase in the number of DCX-labeled cells that was almost four
      and a half-fold. Therefore, aged rats also display an increase in adult
      neurogenesis following seizures.

PMID- 22396877
TI  - Aging, Angiotensin system and dopaminergic degeneration in the substantia nigra.
AB  - For years, the renin-angiotensin system (RAS) was described as a circulating
      humoral system that regulates blood pressure and water homeostasis. Angiotensin
      II (AII) is the most important effector peptide. However, in addition to the
      "classical" humoral RAS there exist local RAS in many tissues and locally formed
      AII activates NADPH-dependent oxidases, which are a major source of superoxide
      and are upregulated in major aging-related diseases such as hypertension,
      diabetes and atherosclerosis. Accordingly, disruption of AII receptors promotes
      longevity in mice. The brain has an independent local RAS, which was also
      initially associated with the central control of blood pressure. However, more
      recent studies have involved brain RAS in brain disorders, including
      neurodegenerative diseases. The interaction between AII and dopamine is
      particularly interesting. Recent evidence suggests that dopamine and AII systems
      directly counterregulate each other in renal cells as well as in the striatum and
      substantia nigra. Dopamine depletion may induce RAS upregulation as a potential
      compensatory mechanism. However, RAS hyperactivation also exacerbates NADPH
      oxidase activity, oxidative stress and the microglial inflammatory response and
      contribute to progression of dopaminergic neuron loss, as observed in recent
      studies with animal models of Parkinson's disease (PD). Aging is the most
      prominent risk factor for PD and other neurodegenerative diseases. Interestingly,
      we observed increased activation of the NADPH oxidase complex and increased
      levels of the pro-inflammatory cytokines in the nigra of aged male rats, which
      was associated with increased RAS activity and was reduced by treatment with AII
      antagonists. We also observed that the lack of oestrogen may act as an additional
      factor for increasing RAS activity in the nigra in aged females, which was
      significantly reduced by treatment with AII antagonists. Manipulation of the
      brain RAS may constitute an effective neuroprotective strategy against the aging
      related risk of dopaminergic degeneration.

PMID- 22396881
TI  - Astrocyte Alterations in the Hippocampus Following Pilocarpine-induced Seizures
      in Aged Rats.
AB  - It is known that the incidence of epilepsy increases with age, but only a few
      studies have investigated the consequences and mechanisms of seizure and epilepsy
      in aged animals. Astrocytic changes are known to directly influence neuronal
      excitability and seizure susceptibility. However, information regarding
      alterations to astrocytes after seizures in aged animals is lacking in the
      literature. In the present study, the density and morphology of astrocytes
      expressing GFAP were investigated in the hippocampus of aged rats that
      experienced status epilepticus induced by pilocarpine. One month after seizures,
      astrocytes in aged rats have increased volume and present activated morphology.
      Despite these morphological changes, the density of astrocytes was not altered in
      the hippocampus of aged rats after seizures.

PMID- 22396882
TI  - m1 Acetylcholine Receptor Expression is Decreased in Hippocampal CA1 region of
      Aged Epileptic Animals.
AB  - In the present study, we investigated the possible additive effects of epilepsy
      and aging on the expression of m1 muscarinic acetylcholine receptors (AChR) in
      the rat hippocampus. Young (3 months) and Aged (20 months) male, Wistar rats were
      treated with pilocarpine to induce status epilepticus (SE). Immunohistochemical
      procedure for m1 AChR detection was performed 2 months after pilocarpine-induced
      SE. In the CA1 pyramidal region m1 AChR staining was significantly decreased in
      aged epileptic animals when compared to young epileptic and aged control rats,
      indicating that the aging effect is worsened by the epileptic condition. However,
      the Nissl-stained cell analysis indicated that the number of pyramidal CA1
      neurons was similarly reduced in both epileptic groups, young and aged animals.
      Therefore, our data suggest that the progressive reduction of m1 AChR expression
      in CA1 pyramidal cells of aged epileptic rats might bear relevance to the
      associated progressive cognitive impairment.

PMID- 22396883
TI  - Aging-induced Seizure-related Changes to the Hippocampal Mossy Fiber Pathway in
      Forebrain Specific BDNF Overexpressing Mice.
AB  - Aging confers an increased risk for developing seizure activity, especially
      within brain regions that mediate learning and synaptic plasticity. Brain derived
      neurotrophic factor (BDNF) is a member of the neurotrophin family that has an
      important role in regulating growth and development of the nervous system. BDNF
      is upregulated after pharmacological seizure induction and this upregulation
      contributes to enhanced excitability of the hippocampal mossy fiber-CA3 pathway,
      which is accompanied by neuropeptide Y (NPY) upregulation. Mice overexpressing a
      BDNF transgene in forebrain neurons provide an avenue for understanding the role
      of neurotrophic support in the aged hippocampus. In this study BDNF transgenic
      (TG) mice were utilized to determine whether increased BDNF expression through
      genetic manipulation resulted in age-related changes in hippocampal excitability
      and NPY expression. Spontaneous behavioral seizures were observed in TG mice, but
      not WT mice, past 5 months of age and the severity of behavioral seizures
      increased with age. Electrophysiological investigation of hippocampal CA3
      activity indicated that slices from aged TG mice (86%), but not age-matched WT
      mice, or young TG mice, showed epileptiform activity in response to either
      repeated paired pulse or high frequency (tetanic) stimulation.
      Electrophysiological results were supported by the observation of robust ectopic
      NPY immunoreactivity in hippocampal mossy fibers of most aged TG mice (57%),
      which was absent in age-matched WT mice and young TG mice. The results from this
      study indicate that forebrain restricted BDNF overexpression produces age-related
      changes in hyperexcitability and NPY immunoreactivity in mossy fiber-CA3 pathway.
      Together, these data suggest that the capability for BDNF to promote
      epileptogenesis is maintained, and may be enhanced, in the aging hippocampus.

PMID- 22396884
TI  - Electrical and Pharmacological Stimuli Reveal a Greater Susceptibility for CA3
      Network Excitability in Hippocampal Slices from Aged vs. Adult Fischer 344 Rats.
AB  - Clinical data and experimental studies in rats have shown that the aged CNS is
      more susceptible to the proconvulsive effects of the excitotoxic glutamate
      analogues kainate (KA) and domoate (DA), which bind high-affinity receptors
      localized at mossy fiber (MF) synapses in the CA3 subregion of the hippocampus.
      Although decreased renal clearance appears to play a role in the hypersensitivity
      of the aged hippocampus to systemically-administered DA, it is unclear if the
      excitability of the CA3 network is also altered with age. Therefore, this study
      monitored CA3 field potential activity in hippocampal slices from aged and adult
      male Fischer 344 rats in response to electrical and pharmacological network
      stimulation targeted to the MF-CA3 circuit. Network challenges with repetitive
      hilar stimulation or bath application of nanomolar concentrations of KA more
      readily elicited excitable network activity (e.g. population spike facilitation,
      multiple population spikes, and epileptiform bursts) in slices from aged vs.
      adult rats, although basal network excitability was comparable between age
      groups. Additionally, exposure to 200 nM KA often abolished epileptiform activity
      and revealed theta or gamma oscillations instead. However, slices from aged rats
      were less sensitive to the rhythmogenic effects of 200 nM KA. Taken together,
      these findings suggest that aging decreases the capacity of the CA3 network to
      constrain the spread of excitability during focal excitatory network challenges.

PMID- 22396885
TI  - Chronic Cellular Hyperexcitability in Elderly Epileptic Rats with Spontaneous
      Seizures Induced by Kainic Acid Status Epilepticus while Young Adults.
AB  - Emerging data indicate that age-related brain changes alter seizure
      susceptibility, seizure-associated neurodegeneration, and responsiveness to AEDs.
      The present study assessed long-term animal survival in the Kainic Acid (KA)
      model along with in-vivo spontaneous seizure frequency, cellular
      hyperexcitability in CA1 in-vitro and in-vivo in subiculum, and responsiveness of
      in-vitro CA1 hyperexcitability to topiramate. Sprague-Dawley male rats were given
      KA to induce convulsive status epilepticus (KA-SE) at 2-3 months of age. The one
      month mortality after KA-SE was 27%. One-month survivor rats had 37% sudden
      unexplained late mortality after KA-SE as compared to none in saline controls
      during their second year of life. In-vivo seizure frequency was examined prior to
      terminal experiments. The diurnal average seizure frequency in the KA-SE group at
      age 2 years was 1.06 +/- 0.24 seizures/hour while no seizures were observed in
      the saline age-matched controls (p<0.001). In-vitro recordings of CA1 pyramidal
      neurons revealed that depolarizing current injection from -60 mV evoked an
      increased number of action potentials in the aged KA-SE group compared to
      controls (p<0.002). Topiramate exhibited dose-dependent inhibition of action
      potential firing evoked by current injections into CA1 pyramidal neurons of KA-SE
      rats. In subiculum, KA-SE rats had frequent interictal spikes associated with
      high frequency oscillations while only rare spontaneous EPSPs were recorded in
      saline controls. Our experiments revealed that the hippocampal formation of aged
      epileptic rats shares features of hyperexcitability previously described in young
      adult epileptic rats using the KA model.

PMID- 22396886
TI  - Immune aging and challenges for immune protection of the graying population.

PMID- 22396887
TI  - Age-related Dysregulation of Inflammation and Innate Immunity: Lessons Learned
      from Rodent Models.
AB  - In the elderly patient population, it has become increasingly evident that immune
      dysregulation is a contributing factor to age-related pathologies and their
      associated morbidity and mortality. In particular, elderly subjects are plagued
      by poor responses to infectious challenge and immunization and are at heightened
      risk for the development of autoimmune, neuroinflammatory and tumor-associated
      pathologies. Rodent models of aging and age-related disorders have been utilized
      to better describe how innate immune cell dysfunction contributes to these
      clinical scenarios. As the elderly population continues to increase in size, use
      of these aging rodent models to study immune dysregulation may translate into
      increased healthy living years for these individuals.

PMID- 22396889
TI  - Age-related Deficiencies in Antigen-Specific CD4 T cell Responses: Lessons from
      Mouse Models.
AB  - Infectious diseases contribute to significant morbidity and mortality in elderly
      populations. One of the major contributing factors to this is age-related
      declines in the immune system that diminish the response o both infections and
      vaccinations. In order to understand how specific changes in the immune system
      influence the generation of immunity in older individuals, immunologists have
      developed aging mouse models that allow for experimental manipulation of immune
      system components. These models have shown that there are dramatic age-related
      changes in naive CD4 T cell function that have the potential to impact a myriad
      of immune responses. In this review, we will summarize these findings on the
      intrinsic changes in CD4 T cell function and discuss how these changes influence
      immunity.

PMID- 22396888
TI  - Aging impairs murine B cell differentiation and function in primary and secondary
      lymphoid tissues.
AB  - Age-related changes in humoral immunity are responsible for the reduced vaccine
      responses observed in elderly individuals. Although aging has been shown to
      affect T cells, dendritic cells and macrophages and these effects significantly
      impact humoral responses, intrinsic alterations in B cells also occur. We here
      provide an overview of age-related changes in mouse B cells. In particular, we
      summarize data from the literature showing age-related changes in B cell
      differentiation in the bone marrow, in B cell marker expression and cell survival
      in the periphery and in the ability to make specific antibodies in both splenic
      and mucosal tissues. Moreover, we summarize the results from our studies showing
      that the ability to undergo class switch recombination, the enzyme activation
      induced cytidine deaminase and the transcription factor E47 are all decreased in
      stimulated B cells from old mice. The defects presented in this review for aged B
      cells should allow the discovery of strategies for improvement of humoral immune
      responses in both humans and mice in the near future.

PMID- 22396890
TI  - Finding Balance: T cell Regulatory Receptor Expression during Aging.
AB  - Aging is associated with a variety of changes to immune responsiveness. Reduced
      protection against infection, reduced responses to vaccination and increased risk
      of autoimmunity are all hallmarks of advanced age. Here we consider how changes
      in the expression of regulatory receptors on the T cell surface contribute to
      altered immunity during aging.

PMID- 22396892
TI  - The origin and implication of thymic involution.
AB  - Age-related regression of the thymus is associated with a decline in naive T cell
      output which is thought to contribute to the reduction in T cell diversity in
      older individuals that is partially responsible for an increase in susceptibility
      and severity of infections, cancers and autoimmune diseases. Thymic involution is
      one of the most dramatic and ubiquitous changes in the ageing immune system, but
      the precise regulators remain anonymous. However, a picture is emerging,
      implicating extrinsic and intrinsic factors that may contribute towards age
      associated thymic involution. In this review we assess the role of the thymic
      microenvironment as a possible target of thymic involution, question whether
      thymocyte development in the aged thymus is functional and explore why the thymus
      involutes.

PMID- 22396891
TI  - Senescence-accelerated Mice (SAMs) as a Model for Brain Aging and
      Immunosenescence.
AB  - The Senescence-Accelerated Mouse (SAM) represents a group of inbred mouse strains
      developed as a model for the study of human aging and age-related diseases.
      Senescence-prone (SAMP) strains exhibit an early onset of age-related decline in
      the peripheral immunity such as thymic involution, loss of CD4(+) T cells,
      impaired helper T cell function, decreased antibody-forming capacity, dysfunction
      of antigen-presenting cells, decreased natural killer activity, increased auto
      antibodies, and susceptibility to virus infection. Senescence-prone SAMP10 mice
      undergo age-related changes in the brain such as brain atrophy, shrinkage and
      loss of cortical neurons, retraction of cortical neuronal dendrites, loss of
      dendritic spines, loss of synapses, impaired learning and memory, depressive
      behavior, accumulation of neuronal DNA damage, neuronal ubiquitinated inclusions,
      reduced hippocampal cholinergic receptors, decreased neurotrophic factors,
      decreased hippocampal zinc and zinc transporters, increased sphyngomyelinase, and
      elevated oxidative-nitrative stress. Recent data indicating increased pro
      inflammatory cytokines in the brain of SAMP10 mice are directing investigators
      toward an integration of immune and neural abnormalities to enhance understanding
      of the principles of brain aging. We highlight how mouse brain cells adopt
      cytokine-mediated responses and how SAMP10 mice are defective in these responses.
      SAMP10 model would be useful to study how age-related disturbances in peripheral
      immunity have an impact on dysregulation of brain tissue homeostasis, resulting
      in age-related neurodegeneration.

PMID- 22396893
TI  - Is Immune Aging a Cause of Disease among the Elderly, or is it a Passive
      Indicator of General Decline of Physiologic Function?

PMID- 22396894
TI  - NF-kappaB in Aging and Disease.
AB  - Stochastic damage to cellular macromolecules and organelles is thought to be a
      driving force behind aging and associated degenerative changes. However, stress
      response pathways activated by this damage may also contribute to aging. The
      IKK/NF-kappaB signaling pathway has been proposed to be one of the key mediators
      of aging. It is activated by genotoxic, oxidative, and inflammatory stresses and
      regulates expression of cytokines, growth factors, and genes that regulate
      apoptosis, cell cycle progression, cell senescence, and inflammation.
      Transcriptional activity of NF-kappaB is increased in a variety of tissues with
      aging and is associated with numerous age-related degenerative diseases including
      Alzheimer's, diabetes and osteoporosis. In mouse models, inhibition of NF-kappaB
      leads to delayed onset of age-related symptoms and pathologies. In addition, NF
      kappaB activation is linked with many of the known lifespan regulators including
      insulin/IGF-1, FOXO, SIRT, mTOR, and DNA damage. Thus NF-kappaB represents a
      possible therapeutic target for extending mammalian healthspan.

PMID- 22396895
TI  - Frailty, inflammation, and immunity.
AB  - Frailty is an important geriatric syndrome that is characterized by multisystem
      dysregulation, leading to decreased physiological reserve and increased
      vulnerability for adverse health outcomes. A large number of studies have shown a
      heightened inflammatory state marked by elevated levels of inflammatory
      molecules, such as IL-6 and C-reactive protein (CRP), and increased counts of
      white blood cell (WBC) and WBC subpopulations in frail older adults. It has been
      postulated that this heightened inflammatory state, or chronic inflammation, may
      play an important role in the pathogenesis of frailty, directly or through its
      detrimental influence to other physiologic systems. Inflammatory and immune
      activation mediated by monocytes and macrophages demonstrated by upregulated
      expression of specific stress responsive inflammatory pathway genes and elevated
      neopterin levels may contribute, at least in part, to this chronically heightened
      inflammatory state in frailty. Decrease in lipopolysaccharide (LPS)-induced
      proliferation of the peripheral blood mononuclear cells (PBMCs), one of the
      functional readouts of the innate immune system, has also been observed in frail
      older adults. In the adaptive immune system, significant frailty-associated
      alterations have been identified in the T-cell compartment including expansion of
      CD8(+) and CCR5(+) T cells and loss of CD28 expression, above and beyond age
      related senescent remodeling. Moreover, frailty is associated with impaired
      antibody responses to pneumococcal and influenza immunization and poor clinical
      protection against influenza infection in community-dwelling older adults. Taken
      together, these findings demonstrate significant inflammatory and immune
      dysregulation in frail older adults and highlight the need for strategies to
      improve the immune function for this vulnerable elderly population.

PMID- 22396896
TI  - Interferon-gamma - Inducible Inflammation: Contribution to Aging and Aging
      Associated Psychiatric Disorders.
AB  - Aging is associated with the chronic, low grade, Th-1 type inflammation. The key
      Th-1 type, pro-inflammatory cytokine, interferon-gamma (IFNG), transcriptionally
      induces the rate-limiting enzyme of tryptophan (TRY) - kynurenine (KYN) pathway,
      indoleamine 2,3- dioxygenase (IDO). Activation of IDO shunts TRY metabolism from
      production of serotonin (substrate of antidepressant effect) and its derivatives:
      N-acetylserotonin (an agonist to the receptors of brain derived neurotropic
      factor), and melatonin (regulator of sleep and other circadian rhythms), towards
      production of KYN and its derivatives (anxiogenic, neurotoxic and pro-oxidant
      factors). Some of kynurenines up-regulate nitric oxide synthase (NOS).
      Concurrently with activation of IDO, IFNG induces guanosine triphosphate
      cyclohydrolase I (GTPCH), the rate limiting enzyme of GTP conversion into BH2
      (and increases formation of a stable derivative of BH2, neopterin, at the expense
      of production of BH4, the mandatory co-factor of NOS). Combination of increased
      NOS activity (by kynurenines) with decreased formation of BH4 leads to the
      uncoupling of NOS with consequent shift of arginine metabolism from biosynthesis
      of NO to formation of superoxide anion and other free radicals, and exacerbation
      of depression, anxiety and cognitive impairment caused by kynurenines.
      Polymorphism of IFNG (+874) T/A gene, that encodes production of IFNG protein,
      impacts the IDO and GTPCH activity that might be assessed in humans by KYN/TRY
      ratio and neopterin concentrations in biological fluids (e.g., blood, urine and
      spinal fluid). The hypothesis of IFNG inducible IDO/GTPCH inflammation cascade
      helps to understand the increased association between aging, inflammation and
      aging-associated psychiatric and medical (insulin resistance, obesity) disorders.
      Evaluation of markers of IFNG-inducible inflammation cascade might be used to
      assess the severity of corresponding behavioral and cognitive changes and the
      efficacy of pharmacological interventions (e.g., IDO inhibitors).

PMID- 22396897
TI  - Effects of Aging on Inflammation and Hemostasis through the Continuum of Critical
      Illness.
AB  - Older age has long been associated with altered inflammation and hemostasis
      regulation. Emerging evidence suggests that age-related differences in
      inflammation and hemostasis abnormalities may play a role in the development of
      and long-term outcomes after critical illness. A better understanding of
      underlying mechanisms may provide new possibilities for therapeutic
      interventions. In this review, we will examine how age-related differences in
      inflammatory and coagulation responses are affected through the continuum of
      healthy state, before infection occurs, to severe sepsis and recovery.

PMID- 22396898
TI  - Immunity, cancer and aging: lessons from mouse models.
AB  - The deterioration of immune function with advancing age is associated with an
      increased incidence of cancer. Most of the studies to evaluate the effect of
      immunotherapy on cancer have been conducted in the young without considering the
      effect of age-associated changes in immune function. Studies from my laboratory
      and others groups indicate that immunotherapeutic interventions could be
      effective in young animals, but that the same therapies are not as effective in
      old animals. The present review summarizes some defects found in the old immune
      system affecting the activation of antitumor immune responses, the strategies
      used to activate a more robust antitumor immune response in the old and the
      description of a preclinical tumor model indicating possible strategies for
      optimization of immunotherapeutic interventions in the old.

PMID- 22396899
TI  - Telomere dysfunction, autoimmunity and aging.
AB  - Immune aging is associated with loss of critical immune functions, such as host
      protection from infection and malignancy. Unexpectedly, immunosenescence also
      renders the host susceptible to inflammation, which may translate into tissue
      damaging disease as the senescent immune system loses its ability to maximize
      inflammatory protection while minimizing inflammatory injury. On the other hand,
      chronic inflammation associated with immune-mediated disease represents a
      profound stress factor for the immune system, affecting cellular turn-over,
      replication and exhaustion. Immune cell longevity is tightly connected to the
      functional integrity of telomeres which are regulated by cell multiplication,
      exposure to oxidative stress and DNA repair mechanisms. Lymphocytes are amongst
      the few cell types that can actively elongate telomeres through the action of
      telomerase. In patients with the autoimmune disease rheumatoid arthritis (RA),
      telomerase deficiency is associated with prematurity of immune aging. Patients
      with RA have other defects in DNA repair mechanisms, including the kinase Ataxia
      telangiectasia mutated (ATM), critically involved in the repair of DNA double
      strand breaks. ATM deficiency in RA shortens lymphocyte survival. Dynamics of
      telomeric length and structure are beginning to be understood and have distinct
      patterns in different autoimmune diseases, suggesting a multitude of molecular
      mechanisms defining the interface between chronic immune stimulation and
      progressive aging of the immune system.

PMID- 22396900
TI  - Down syndrome: is it really characterized by precocious immunosenescence?
AB  - The immune system declines with aging, leading to an increased susceptibility to
      infections and higher incidence and progression of autoimmune phenomena and
      neoplasia. Down syndrome prematurely shows clinical manifestations that are
      normally seen with aging. This review provides a concise overview of
      abnormalities in the adaptive immune system of Down syndrome in comparison to
      normal and precocious (Progeria syndromes) aging. Clinical signs and
      immunological changes are reviewed. We challenge the hypothesis that the
      immunological abnormalities in Down syndrome should be interpreted as precocious
      immunosenescence.

PMID- 22396901
TI  - Iontophoresis: a potential emergence of a transdermal drug delivery system.
AB  - The delivery of drugs into systemic circulation via skin has generated much
      attention during the last decade. Transdermal therapeutic systems propound
      controlled release of active ingredients through the skin and into the systemic
      circulation in a predictive manner. Drugs administered through these systems
      escape first-pass metabolism and maintain a steady state scenario similar to a
      continuous intravenous infusion for up to several days. However, the excellent
      impervious nature of the skin offers the greatest challenge for successful
      delivery of drug molecules by utilizing the concepts of iontophoresis. The
      present review deals with the principles and the recent innovations in the field
      of iontophoretic drug delivery system together with factors affecting the system.
      This delivery system utilizes electric current as a driving force for permeation
      of ionic and non-ionic medications. The rationale behind using this technique is
      to reversibly alter the barrier properties of skin, which could possibly improve
      the penetration of drugs such as proteins, peptides and other macromolecules to
      increase the systemic delivery of high molecular weight compounds with controlled
      input kinetics and minimum inter-subject variability. Although iontophoresis
      seems to be an ideal candidate to overcome the limitations associated with the
      delivery of ionic drugs, further extrapolation of this technique is imperative
      for translational utility and mass human application.

PMID- 22396902
TI  - Synthesis by ring-closing metathesis and cytotoxic evaluation of novel
      thienylmacrolactones.
AB  - This paper describes the synthesis and biological evaluation of macrolactones
      containing a thienyl substituent as simple analogues of epothilones. The
      compounds were prepared in a brief and efficient manner from thiophene-2
      carbaldehyde using a ring-closing metathesis with Grubbs I or Grubbs II catalyst
      as the key step. The target lactones showed only insignificant cytotoxicity,
      while an intermediate simple thienyl carbinol showed very promising cytotoxicity.

PMID- 22396903
TI  - Synthesis of New 6-{[omega-(Dialkylamino(heterocyclyl)alkyl]thio}-3-R-2H
      [1,2,4]triazino[2,3-c]quinazoline-2-ones and Evaluation of their Anticancer and
      Antimicrobial Activities.
AB  - Several novel 6-thio-3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-based
      compounds containing an omega-(dialkylamino(heterocyclyl)]alkyl fragment were
      synthesized to examine their anticancer activity. Some of the 6-{[omega-(hetero
      cyclyl)alkyl]thio}-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones (3.1-3.10)
      were obtained by the nucleophilic substitution of 6-[omega-halogenalkyl]thio-3-R
      2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones (2.1-2.8) with azaheterocycles.
      Alternatively, compounds 3.1-3.22 were synthesized by alkylation of 3-R-6-thio-2H
      [1,2,4]triazino[2,3-c]quinazoline-2-ones potassium salts (1.1-1.4) with (2
      chloroethyl)-N,N-dialkylamine hydrochlorides or 1-(2-chloroethyl)heterocycle
      hydrochlorides. The structures of compounds were elucidated by (1)H, (13)C NMR,
      LC-MS and EI-MS analysis. Then anticancer and antibacterial, bioluminescence
      inhibition of Photobacterium leiognathi Sh1 activities of the substances were
      tested in vitro. It was found that compound 3.18 possessed a wide range of
      anticancer activity against 27 cell lines of cancer: non-small cell lung, colon,
      CNS, ovarian, renal, prostate, breast, melanoma and leukemia (log GI(50) < 
      5.65). The "structure-activity" relationship was discussed. COMPARE analysis for
      synthesized anticancer active compounds was performed.

PMID- 22396904
TI  - Synthesis and characterization of organic impurities in bortezomib anhydride
      produced by a convergent technology.
AB  - A profile of impurities in bortezomib anhydride, produced by a recently developed
      convergent technology, has been characterized. HPLC-MS analysis of the drug
      essence revealed three impurities: an epimer of bortezomib, resulting from
      partial racemization of l-phenylalanine's stereogenic center during the chemical
      synthesis, and two epimeric products of oxidative degradation of bortezomib, in
      which boron is replaced by the OH group. The impurities were obtained by chemical
      synthesis and characterized by physical methods.

PMID- 22396905
TI  - Simple and sensitive stability-indicating ion chromatography method for the
      determination of cyclopropylamine in nevirapine and moxifloxacin hydrochloride
      drug substances.
AB  - A simple and sensitive ion chromatography method has been developed for the
      determination of cyclopropylamine (CPA) in nevirapine (NEV) and moxifloxacin HCl
      (MOX) pharmaceutical drug substances. Efficient chromatographic separation was
      achieved on a Metrosep C4, 5 MUm (250 mm * 4.0 mm) column. The mobile phase
      consists of 5 mM hydrochloric acid containing 10% (v/v) acetonitrile and was
      delivered in an isocratic mode at a flow rate of 0.9 mL min(-1) at 27 degrees C.
      A conductometric detector was used for the detection of the analyte. The drug
      substances were subjected to stress conditions including oxidation, thermal,
      photolytic and humidity for the evaluation of the stability-indicating nature of
      the method. The method was validated for specificity, precision, linearity,
      accuracy and solution stability. The limit of detection (LOD) and limit of
      quantification (LOQ) values are 0.10 MUg mL(-1) and 0.37 MUg mL(-1) respectively.
      The linearity range of the method is between 0.37 MUg mL(-1) and 1.5 MUg mL(-1)
      and the correlation coefficient is found to be 0.9971. The average recoveries of
      CPA in NEV and MOX are 97.0% and 98.0%, respectively.

PMID- 22396906
TI  - Validated HPLC Method for Concurrent Determination of Antipyrine, Carbamazepine,
      Furosemide and Phenytoin and its Application in Assessment of Drug Permeability
      through Caco-2 Cell Monolayers.
AB  - The present work explains the development and validation of a simple, rapid and
      sensitive liquid chromatographic method for the simultaneous determination of
      antipyrine (ANT), carbamazepine (CBZ), furosemide (FSD) and phenytoin (PHTN).
      Chromatographic analysis was carried out by a reversed phase technique on a C18
      column, using water pH 3.0 and 50:50 mixtures of methanol and acetonitrile (58:42
      v/v) as the mobile phase, at a flow-rate of 1.0 ml/min and a column temperature
      of 40 degrees C. Detection was carried out at 205 nm for CBZ and PHTN and at 230
      nm for ANT and FSD. The proposed method was evaluated for validation parameters
      including linearity, range, accuracy, precision, limit of detection (LOD), limit
      of quantification (LOQ) and specificity. Elution of drugs ANT, FSD, PHTN, and CBZ
      was observed at 4.1, 5.1, 12.3 and 13.5 min, respectively. The method was found
      to be linear (R(2) >= 0.999) in the concentration range of 5-100 MUM, with an
      acceptable accuracy and relative standard deviation. Results of intra- and inter
      day validation (n=3) showed the method to be efficient for routine determination
      of these permeability markers in Caco-2 cell monolayer permeability studies. The
      method was successfully utilized for determination of standard compounds in Caco
      2 permeability experiments.

PMID- 22396907
TI  - A New Rapid and Sensitive Stability-Indicating UPLC Assay Method for Tolterodine
      Tartrate: Application in Pharmaceuticals, Human Plasma and Urine Samples.
AB  - A new rapid, simple, sensitive, selective and accurate reversed-phase stability
      indicating Ultra Performance Liquid Chromatography (RP-UPLC) technique was
      developed for the assay of Tolterodine Tartrate in pharmaceutical dosage form,
      human plasma and urine samples. The developed UPLC method is superior in
      technology to conventional HPLC with respect to speed, solvent consumption,
      resolution and cost of analysis. Chromatographic run time was 6 min in reversed
      phase mode and ultraviolet detection was carried out at 220 nm for
      quantification. Efficient separation was achieved for all the degradants of
      Tolterodine Tartrate on BEH C18 sub-2-MUm Acquity UPLC column using
      Trifluoroacetic acid and acetonitrile as organic solvent in a linear gradient
      program. The active pharmaceutical ingredient was extracted from tablet dosage
      form using a mixture of acetonitrile and water as diluent. The calibration graphs
      were linear and the method showed excellent recoveries for bulk and tablet dosage
      form. The test solution was found to be stable for 40 days when stored in the
      refrigerator between 2 and 8  degrees C. The developed UPLC method was validated
      and meets the requirements delineated by the International Conference on
      Harmonization (ICH) guidelines with respect to linearity, accuracy, precision,
      specificity and robustness. The intra-day and inter-day variation was found be
      less than 1%. The method was reproducible and selective for the estimation of
      Tolterodine Tartrate. Because the method could effectively separate the drug from
      its degradation products, it can be employed as a stability-indicating one.

PMID- 22396908
TI  - Stress degradation studies on varenicline tartrate and development of a validated
      stability-indicating HPLC method.
AB  - A simple, rapid and stability-indicating reversed-phase liquid chromatographic
      method was developed for the assay of varenicline tartrate (VRT) in the presence
      of its degradation products generated from forced decomposition studies. The HPLC
      separation was achieved on a C18 Inertsil column (250 mm * 4.6 mm i.d. particle
      size is 5 MUm) employing a mobile phase consisting of ammonium acetate buffer
      containing trifluoroacetic acid (0.02M; pH 4) and acetonitrile in gradient
      program mode with a flow rate of 1.0 mL min(-1). The UV detector was operated at
      237 nm while column temperature was maintained at 40  degrees C. The developed
      method was validated as per ICH guidelines with respect to specificity,
      linearity, precision, accuracy, robustness and limit of quantification. The
      method was found to be simple, specific, precise and accurate. Selectivity of the
      proposed method was validated by subjecting the stock solution of VRT to acidic,
      basic, photolysis, oxidative and thermal degradation. The calibration curve was
      found to be linear in the concentration range of 0.1-192 MUg mL(-1) (R(2) =
      0.9994). The peaks of degradation products did not interfere with that of pure
      VRT. The utility of the developed method was examined by analyzing the tablets
      containing VRT. The results of analysis were subjected to statistical analysis.

PMID- 22396909
TI  - New Stability-Indicating RP-HPLC Method for Determination of Diclofenac Potassium
      and Metaxalone from their Combined Dosage Form.
AB  - A simple, precise and accurate isocratic RP-HPLC stability-indicating assay
      method has been developed to determine diclofenac potassium and metaxalone in
      their combined dosage forms. Isocratic separation was achieved on a Hibar-C(18),
      Lichrosphere-100((r)) (250 mm * 4.6 mm i.d., particle size 5 MUm) column at room
      temperature in isocratic mode, the mobile phase consists of methanol: water
      (80:20, v/v) at a flow rate of 1.0 ml/min, the injection volume was 20 MUl and UV
      detection was carried out at 280nm. The drug was subjected to acid and alkali
      hydrolysis, oxidation, photolysis and heat as stress conditions. The method was
      validated for specificity, linearity, precision, accuracy, robustness and system
      suitability. The method was linear in the drug concentration range of 2.5-30
      MUg/ml and 20-240 MUg/ml for diclofenac potassium and metaxalone, respectively.
      The precision (RSD) of six samples was 0.83 and 0.93% for repeatability, and the
      intermediate precision (RSD) among six-sample preparation was 1.63 and 0.49% for
      diclofenac potassium and metaxalone, respectively. The mean recoveries were
      between 100.99-102.58% and 99.97-100.01% for diclofenac potassium and metaxalone,
      respectively. The proposed method can be used successfully for routine analysis
      of the drug in bulk and combined pharmaceutical dosage forms.

PMID- 22396910
TI  - Simultaneous Determination of Sitagliptin Phosphate Monohydrate and Metformin
      Hydrochloride in Tablets by a Validated UPLC Method.
AB  - A novel approach was used to develop and validate a rapid, specific, accurate and
      precise reverse phase ultra performance liquid chromatographic (UPLC) method for
      the simultaneous determination of Sitagliptin phosphate monohydrate and Metformin
      hydrochloride in pharmaceutical dosage forms. The chromatographic separation was
      achieved on Aquity UPLC BEH C8 100 * 2.1 mm, 1.7 MUm, column using a buffer
      consisting of 10 mM potassium dihydrogen phosphate and 2 mM hexane-1-sulfonic
      acid sodium salt (pH adjusted to 5.50 with diluted phosphoric acid) and
      acetonitrile as organic solvent in a gradient program. The flow rate was 0.2 mL
      min(-1) and the detection wavelength was 210 nm. The limit of detection (LOD) for
      Sitagliptin phosphate monohydrate and Metformin hydrochloride was 0.2 and 0.06
      MUg mL(-1), respectively. The limit of quantification (LOQ) for Sitagliptin
      phosphate monohydrate and Metformin hydrochloride was 0.7 and 0.2 MUg mL(-1),
      respectively. This method was validated with respect to linearity, accuracy,
      precision, specificity and robustness. The method was also found to be stability
      indicating.

PMID- 22396911
TI  - A Validated Stability-Indicating RP-UPLC Method for Simultaneous Determination of
      Desloratadine and Sodium Benzoate in Oral Liquid Pharmaceutical Formulations.
AB  - A novel, sensitive and selective stability-indicating gradient reverse phase
      ultra performance liquid chromatographic method was developed and validated for
      the quantitative determination of desloratadine and sodium benzoate in
      pharmaceutical oral liquid formulation. The chromatographic separation was
      achieved on Acquity BEH C8 (100 mm * 2.1 mm) 1.7 MUm column by using mobile phase
      containing a gradient mixture of solvent A (0.05 M KH(2)PO(4) and 0.07 M
      triethylamine, pH 3.0) and B (50:25:25 v/v/v mixture of acetonitrile, methanol
      and water) at flow rate of 0.4 mL/min. Column temperature was maintained at 40
      degrees C and detection was carried out at a wavelength of 272 nm. The described
      method shows excellent linearity over a range of 0.254 MUg/mL to 76.194 MUg/mL
      for desloratadine and 1.006 MUg/mL to 301.67 MUg/mL for sodium benzoate. The
      correlation coefficient for desloratadine and sodium benzoate was more than
      0.999. To establish stability-indicating capability of the method, drug product
      was subjected to the stress conditions of acid, base, oxidative, hydrolytic,
      thermal and photolytic degradation. The degradation products were well resolved
      from desloratadine and sodium benzoate. The developed method was validated as per
      international ICH guidelines with respect to specificity, linearity, LOD, LOQ,
      accuracy, precision and robustness.

PMID- 22396912
TI  - Pharmacokinetics and Excretion Studies on CDRI-85/92, an Antiulcer Proton Pump
      Inhibitor.
AB  - CDRI 85/92 is an antiulcer pharmacophore and a proton pump inhibitor, which is in
      an advanced stage of preclinical trials. In view of its importance,
      pharmacokinetic and excretion were studied in Sprague Dawley rats after
      administering 20 mg/kg oral and intravenous doses. The compound was detectable in
      the serum samples as early as 5 min post-oral administration. The compound was
      eliminated slowly from serum with an elimination half-life of 2.1 h. Following
      the 20 mg/kg oral dose, maximum serum concentration (C(max)) was found to be
      469.28 +/- 45.52 ng/ml after 1.0 h. Based on AUC values, the absolute
      bioavailability of the CDRI 85/92 was 70.5% after oral administration. It was
      found to be excreted in urine (~15% of the dose) in intravenously treated (bile
      duct cannulated as well as noncannulated) rats, whereas bile and feces depicted
      insignificant levels of the compound.

PMID- 22396913
TI  - Relevance of serum levels of interleukin-6 and syndecan-1 in patients with
      hepatocellular carcinoma.
AB  - Syndecan-1 is a trans-membrane heparan sulfate proteoglycan that localizes in
      epithelial cells and has been shown to be present in normal hepatocytes. It is
      thought to be involved in processes such as cell growth, differentiation and
      adhesion. However, the clinical data regarding syndecan-1 in patients with
      hepatocellular carcinoma (HCC) are scarce and controversial. Therefore, we need
      to evaluate the effects of HCC on the serum levels of syndecan-1. Thus, 40
      patients with HCC and 31 patients with liver cirrhosis were physically examined.
      Blood samples were taken for measurements of routine markers (sGPT, sGOT,
      bilirubin, albumin, and alpha-fetoprotein), as well as serum levels of
      interleukin (IL)-6 and syndecan-1. Patients with liver cirrhosis showed
      significant increase in serum IL-6 as compared with HCC patients and the control
      subjects. Serum level of syndecan-1 was significantly increased in HCC patients
      as compared with the cirrhotic and control groups. In addition, significant
      positive correlations between syndecan-1 and serum levels of ALT, AST in HCC
      patients were found. Moreover, syndecan-1 increased significantly with increasing
      stage of Barcelona-Clinic Liver Cancer Group diagnostic and treatment strategy.
      In conclusion, the development of HCC is accompanied by a significant elevation
      in serum syndecan-1 levels. The increase in serum syndecan-1 may be linked with
      progression of HCC.

PMID- 22396914
TI  - Antimicrobial and Safety Properties of Lactobacilli Isolated from two Cameroonian
      Traditional Fermented Foods.
AB  - Twenty-one Lactobacillus isolates from "Sha'a" (a maize - based fermented
      beverage) and "Kossam" (traditionally fermented cow milk) were selected in
      accordance with their antagonistic activities and tested for their
      bacteriocinogenic potential as well as safety properties. These isolates were
      preliminarily identified as Lactobacillus plantarum (62%), Lactobacillus
      rhamnosus (24%), Lactobacillus fermentum (10%) and Lactobacillus coprophilus (4%)
      based on phenotypic characteristics and rep-PCR genomic fingerprinting. Twelve
      (57.1%) out of the 21 strains tested were found to be bacteriocin producers, as
      revealed by the sensitivity of their antimicrobial substances to proteolytic
      enzymes (Trypsin, Proteinase K) and inhibition of other Lactobacillus spp. These
      bacteriocinogenic strains showed no positive haemolytic and gelatinase activities
      and proved to be sensitive to penicillin G, ampicillin, tetracycline,
      erythromycin, amoxicillin, chloramphenicol, co-trimoxazole and doxycyclin, but
      resistant to ciprofloxacin and gentamicin. The bacteriocins showed a broad
      inhibitory activity against Gram-positive and Gram-negative pathogenic bacteria,
      several of which are classified as especially dangerous by the World Health
      Organization, as well as Multidrug-resistant strains. These include
      Staphylococcus aureus, Salmonella enterica subsp. enterica serovare Typhi,
      Bacillus cereus, Streptococcus mutans, Escherichia coli, Pseudomonas aeruginosa,
      Klebsiella pneumoniae and Shigella flexneri. These Lactobacillus strains are
      promising candidates for use as protective cultures in food fermentation.

PMID- 22396915
TI  - Screening and HPLC-Based Activity Profiling for New Antiprotozoal Leads from
      European Plants.
AB  - Based on a survey of remedies used in Renaissance Europe to treat malaria, we
      prepared and screened a library of 254 extracts from 61 plants for antiplasmodial
      activity in vitro. HPLC-based activity profiling was performed for targeted
      identification of active constituents in extracts. One of the most remarkable
      results was the identification of onopordopicrin, a germacranolide sesquiterpene
      lactone isolated from Arctium nemorosum as a potent inhibitor of P. falciparum
      with an IC(50) of 6.9 MUM. It was tested similarly against Trypanosoma brucei
      rhodesiense, the parasite which causes African sleeping sickness. With an IC(50)
      of 0.37 MUM, onopordopicrin was one of the most potent natural products reported
      so far. Cytotoxicity was determined against rat myoblast L6 cells (IC(50): 3.06).

PMID- 22396916
TI  - Enhanced Bioavailability and Dissolution of Atorvastatin Calcium from Floating
      Microcapsules using Minimum Additives.
AB  - Atorvastatin calcium, a lipid-lowering drug, is much less bioavailable because of
      reduced solubility in acidic media. Multiple-unit floating microcapsules of
      Atorvastatin calcium (ATC) were developed to expand the gastric residence time of
      the drug, as ATC has maximum rate of absorption in the upper GI tract. Floating
      microcapsules were prepared by Emulsion-solvent evaporation technique through
      incorporation of dioctyl sodium sulphosuccinate (DSS) as a dissolution enhancer.
      The microcapsules were assessed for shape, size, drug entrapment efficiency,
      stability and in-vitro drug dissolution rate and were subjected to SEM, DSC and
      PXRD studies. The ATC-loaded floating microcapsules were spherical in shape and
      had the particle size of about 28.10 MUm and drug-loading efficiency of about
      96.55 %. The floating microspheres containing DSS had significantly higher drug
      dissolution rates than those without DSS. The best formulation, AT4, consisting
      of Ethyl cellulose, DSS and Poly Ox(r), had a maximum drug dissolution rate of
      97.86 %, as compared to Storvas 80 mg (Ranbaxy Ltd, as a reference) which had a
      rate of only 54% during a period of 12 h in acidic media. A pharmacokinetic study
      performed on albino rabbits illustrates that the bioavailability of AT4 floating
      microcapsules significantly increased to nearly 1.7 times that of Storvas 80 mg.
      The present study indicates that the use of multi-unit floating microcapsules for
      delivery of ATC can improve its bioavailability.

PMID- 22396917
TI  - Osmotically regulated two-compartment asymmetric membrane capsules for
      simultaneous controlled release of anti-hypertensive drugs.
AB  - In the present study, asymmetric membrane capsules (AMCs) with two compartments
      were successfully developed for simultaneous delivery of two poorly water-soluble
      drugs, Atenolol and Amlodipine Besylate, by using solubility modulation approach.
      Scanning electron microscopy (SEM) before dissolution showed presence of outer
      dense region and inner porous region for the prepared asymmetric membrane and the
      pore size increased after dissolution for both outer and inner layer. Diffuse
      reflectance spectroscopy (DRS) showed no incompatibility between the drug(s) and
      the excipients used in the study. The developed system was able to control the
      release of ATN and AMB by increasing the solubility through buffering agents of
      different strengths (0.25N to 1.0N). As the level of buffering agent was
      increased, the solubility of drugs also increased inside the asymmetric membrane
      capsule. The developed system was independent of the agitation intensity of the
      dissolution fluid but was dependent on the polymer diffusibility and osmotic
      pressure of the media, which clearly stated that osmotic pumping was the primary
      mechanism of drug(s) release from AMCs. The results of in-vitro demonstration of
      effect of membrane thickness on dissolution fluid entering AMCs showed that as
      the membrane thickness increased the volume of dissolution fluid entering into
      AMC decreased. The release kinetic studies of different formulations of AMCs
      showed that formulation code six, which consists of the highest amount of osmotic
      agents and optimum amount of buffering agents, was the best formulation, and it
      followed zero order release kinetics (r(2)=0.9990 for ATN and r(2)=0.9988 for
      AMB).

PMID- 22396918
TI  - ADHD guidelines - flaws in the literature and the need to scrutinise the
      evidence.
AB  - On 25 October 2011, the National Health and Medical Research Council (NHMRC)
      announced that the draft Australian guidelines on attention deficit hyperactivity
      disorder (ADHD) remain unendorsed. The status of the draft guidelines has been in
      limbo since November 2009, when conflict of interest sanctions were announced
      against a key United States based researcher whose work had been heavily
      referenced in the provisional document. As an interim measure until questions
      about the integrity of the research are resolved, the NHMRC is developing
      clinical practice points to assist concerned parents and medical professionals.

PMID- 22396919
TI  - Osteoporosis.
AB  - From April 2010 to March 2011 in BEACH, osteoporosis was managed at a rate of 6
      per 1000 general practice encounters, suggesting an average 708,000 osteoporosis
      patient-doctor encounters per year nationally.

PMID- 22396920
TI  - Vitamin D and the musculoskeletal health of older adults.
AB  - BACKGROUND: The scientific literature related to vitamin D and bone health in
      older adults is extensive. OBJECTIVE: This article aims to summarise key practice
      points regarding vitamin D and bone health in older adults, relevant to general
      practitioners, and to provide an overview of the background literature to enable
      GPs to appreciate the extent of the supporting evidence. DISCUSSION: Vitamin D
      supplementation can prevent falls, particularly in the vitamin D deficient
      elderly. However, adequate vitamin D levels and dietary calcium intake are needed
      for effective primary fracture prevention with greatest benefits occurring in the
      elderly with vitamin D deficiency and/or low dietary calcium intakes. For
      secondary fracture prevention, ie. preventing further fractures in the elderly
      who have already sustained a fragility fracture, specific anti-osteoporosis
      treatment is necessary. However, to maximise the benefits of these medications,
      vitamin D deficiency should be corrected and adequate dietary calcium consumed.

PMID- 22396921
TI  - Paget disease of bone - an update.
AB  - BACKGROUND: Paget disease of bone is the most common metabolic bone disease after
      osteoporosis, affecting 2-4% of adults over 55 years of age. Its aetiology is
      only partly understood, but includes both genetic and environmental factors.
      OBJECTIVE: This article outlines the clinical features, diagnosis and management
      options for Paget disease of bone. DISCUSSION: The disease may be asymptomatic,
      found incidentally on radiography or biochemistry, or present with bone pain,
      deformity, fracture or other complications. Bisphosphonate therapy is indicated
      for patients with symptomatic disease and should also be considered in patients
      whose sites of disease suggest a risk of complications, such as long bones,
      vertebrae or base of the skull. The treatment of choice is a single infusion of
      zoledronic acid; courses of oral alendronate (3-6 months) or risedronate (2
      months) are also effective.

PMID- 22396922
TI  - Osteoporosis - prevention and detection in general practice.
AB  - BACKGROUND: Osteoporosis causes a large and growing health burden in Australia.
      Effective treatments are available, but these are inconsistently implemented.
      There is some inconsistency in expert advice on who should be recommended to have
      bone densitometry. OBJECTIVE: This review draws on the available high level
      evidence for what works in prevention and discusses the rationale for using
      absolute risk estimations for decision making. DISCUSSION: Effective
      interventions for the prevention and early intervention of osteoporosis have not
      been delivered as widely as they should be. Efforts should be focused on offering
      treatment to those groups with the highest risk of fracture, particularly those
      that have had a fragility fracture. There is synergy in the lifestyle
      recommendations for bone health with other aspects of health, so these should be
      addressed as thoroughly as possible.

PMID- 22396924
TI  - Cardiac stress testing - stress electrocardiography and stress echocardiography.
AB  - Coronary artery disease (CAD) affects over 600,000 Australians and is implicated
      in approximately one in 5 deaths. Coronary angiography is the gold standard for
      identifying CAD, although it is invasive and not without risk of complication.
      Cardiac stress testing is useful in the risk stratification of chest pain; noting
      that 15-39% of angiograms performed are normal.

PMID- 22396923
TI  - Osteoporosis - pharmacological prevention and management in older people.
AB  - BACKGROUND: Osteoporosis remains undertreated in Australian primary care, with as
      few as 30% of postmenopausal women with a fracture and 10% of men with
      osteoporosis receiving pharmacological treatment. OBJECTIVE: This article
      presents an overview of the pharmacological management of osteoporosis in older
      people in the general practice setting. DISCUSSION: Lifestyle factors and
      ensuring adequate calcium and vitamin D intake are important in preventing and
      treating osteoporosis. Pharmacological treatments are recommended for patients
      with a minimal trauma fracture, for those aged 70 years or over with a T-score of
      -3.0 or lower, or for those who are currently taking prolonged high dose
      corticosteroids and who have a T-score of -1.5 or lower. Bisphosphonates are
      recommended as first line therapy for established postmenopausal osteoporosis.
      Medicine selection is guided by patient gender, menopausal status, medical and
      fracture history, patient preference and eligibility for government subsidy.

PMID- 22396925
TI  - Tick bite - a case study.
AB  - A woman, 84 years of age, presented to our southeastern Queensland general
      practice for removal of an engorged tick from her right external auditory meatus,
      thought to have been present for several days. She re-presented 3 days later with
      a right facial nerve palsy that affected her frontalis muscle only (Figure 1).
      The facial nerve palsy resolved spontaneously over the next 7 days (Figure 2).

PMID- 22396926
TI  - Contact tracing for STIs - new resources and supportive evidence.
AB  - BACKGROUND: Contact tracing of sexual partners is an important part of the
      clinical management of sexually transmissible infections (STIs) and initiation of
      contact tracing is the responsibility of the diagnosing clinician. Research has
      shown that some general practitioners would like to improve their skills in this
      area. OBJECTIVE: This article outlines new resources and evidence to assist GPs
      to initiate contact tracing when a patient is diagnosed with an STI. DISCUSSION:
      Most STIs are diagnosed in general practice so the involvement of GPs in contact
      tracing is crucial. The aims of contact tracing are to prevent re-infection of
      the index case, minimise complications and reduce the population prevalence of
      STIs in the community. Contact tracing begins with a conversation with the index
      patient about informing their sexual partner(s). The patient can then decide to
      inform their own contacts (patient referral) or organise for someone else to
      inform them (provider referral). Initiating contact tracing in general practice
      can be particularly effective if the resources and methods are tailored to the
      specific needs of the index patient. New resources provide clearer guidelines and
      tools to assist GPs in this area.

PMID- 22396927
TI  - Intellectual disability, sexuality and sexual abuse prevention - a study of
      family members and support workers.
AB  - BACKGROUND: People with intellectual disability experience difficulty forming
      intimate relationships and are prone to sexual exploitation and abuse. This study
      sought information from people involved in the care of adults with intellectual
      disability regarding how they supported them in the areas of sexuality,
      relationships and abuse prevention. METHODS: Semistructured interviews and focus
      groups were held with 28 family members and paid support workers caring for
      adults with intellectual disabilities. Interviews and focus groups were audio
      recorded, transcribed, coded and analysed qualitatively. RESULTS: Major themes
      emerging included views on sexuality and intellectual disability, consent and
      legal issues, relationships, sexual knowledge and education, disempowerment,
      exploitation and abuse, sexual health and parenting. DISCUSSION: People with
      intellectual disability were described as lonely, disempowered and vulnerable to
      abuse. The sex industry, internet and mobile telephones were identified as new
      forms of risk. While this study looked at the views of both family members and
      support workers, the sample was too small to identify any meaningful differences
      between the two groups.

PMID- 22396928
TI  - Metal fume fever - a case review of calls made to the Victorian Poisons
      Information Centre.
AB  - OBJECTIVE: To determine the epidemiology of metal fume fever over an extended
      period in Victoria, Australia. METHODS: A retrospective case review of all metal
      fume fever related calls to the Victorian Poisons Information Centre. Specific
      defined criteria were used to identify cases of metal fume fever and a set of
      data points extracted for each. RESULTS: Eighty-four (99%) of the cases involved
      adults. Fifty-three percent of exposures occurred in the workplace. The most
      frequent day of symptom manifestation was Monday (24%). All of the calls
      concerned people involved in welding metal with subsequent inhalation of fumes.
      DISCUSSION: Calls were most common at the beginning of the week, reflecting the
      previously described phenomena of increased symptoms occurring after a period on
      nonexposure (loss of tolerance). Workplace safety and education is key to
      prevention of metal fume fever. Medical profession education may help prevent
      occurrences of metal fume fever at home, at school and in the workplace.

PMID- 22396929
TI  - The NSW Refugee Health Service - improving refugee access to primary care.
AB  - People of refugee background living in Australia can have significant physical
      and emotional healthcare needs. However, their ability to access mainstream
      health services, including general practitioners, may be limited by factors such
      as lack of familiarity with the health system, language and cultural barriers,
      and cost. There are a number of ways in which GPs can be involved and various
      sources of support available. With minor modifications to practice logistics and
      consultations, GPs can provide beneficial and rewarding healthcare for this
      disadvantaged group of families and individuals.

PMID- 22396930
TI  - Quality in general practice - definitions and frameworks.
AB  - BACKGROUND: In 2010, the federal government introduced the first comprehensive
      national policy statement for primary healthcare in Australia. This policy
      identifies key reform initiatives with the overall aim of improving the quality
      of healthcare. However, what constitutes quality and how to measure it is the
      subject of ongoing debate both nationally and internationally. OBJECTIVE: In this
      article we explore the current experience of defining quality and implementing
      quality frameworks in general practice settings in New Zealand, the United
      Kingdom, Germany and Australia. DISCUSSION: There are multiple and varying
      definitions of quality in general practice, but most emphasise patient experience
      as their primary focus. The quality frameworks used in the countries investigated
      are all based on Donabedian's systems-based framework of structure, process and
      outcome. Implementation and application varies however, with top-down approaches
      in New Zealand and the United Kingdom, and bottom-up approaches in Germany.
      Provision of high quality care is the primary goal in all the systems described.
      External standards, targets and incentives are important initiatives, but
      countries with high quality general practice excel at empowering general practice
      to own the quality agenda.

PMID- 22396931
TI  - Point of care or clinical ultrasound?

PMID- 22396932
TI  - Ultrasound of the median arcuate ligament syndrome: a new approach to diagnosis.
AB  - INTRODUCTION: The currently accepted pathophysiological concept behind median
      arcuate ligament syndrome (MALS) is vascular compromise by atypically positioned
      median arcuate ligament. Despite many articles on MALS, only sparse data on the
      outcome in general and the rather poor outcome after intervention have been
      reported and this makes at least questionable the current concepts of the
      underlying disease. MATERIAL AND METHODS: A total of 364 patients with suspected
      celiac trunk pathology underwent a standardized ultrasound assessment procedure:
      suspected diagnostic features for MALS such as typically elevated peak flow
      velocities (PV) in the celiac trunk or atypical celiac trunk deflection-angles
      (DA) were defined in patients and in 20 matched volunteers. RESULTS: All the 6
      retrospectively clearly diagnosed MALS-patients as well as 40% (8/20) of
      volunteers presented a DA of over 50 degrees . MALS-patients presented a mean
      inspiratory PV of 172cm/s (+/- 40.9 cm/s), a mean expiratory PV of 425cm/s (+/
      130.1 cm/s) with a PV-amplitude of 249.1% (+/-68.9%). Volunteers presented a mean
      inspiratory PV of 126.9cm/s (+/-42 cm/s), a mean expiratory PV of 209.9cm/s (+/
      80.1 cm/s) with a PV-amplitude of 169.4% (+/-54.3%). CONCLUSIONS: The combination
      of a maximum expiratory PV of over 350 cm/s and a DA higher than 50 degrees 
      seems to be a most reliable indicator for MALS in this small series of patients.
      Based on these data we propose that functional ultrasound should be the first
      line in screening for MALS. However, a clear pathophysiological definition of
      MALS remains still obscure.

PMID- 22396933
TI  - Markers of preclinical vascular disease and left ventricular diastolic
      dysfunction in patients with HIV infection.
AB  - BACKGROUND: HIV infected patients have an increased cardiovascular risk that may
      be linked not only to the infection itself but also to the metabolic side effects
      of the antiretroviral therapy. AIM: The aim of our study was to determine markers
      of aortic arterial stiffness, carotid intima-media thickness (IMT) and parameters
      of left ventricular diastolic function and to establish the relationship between
      these vascular and cardiac parameters in HIV infected patients. MATERIAL AND
      METHOD: In this cross sectional case control study 43 patients with HIV infection
      and 25 healthy controls, matched for age and sex were enrolled. Aortic pulse wave
      velocity (PWV) and augmentation index (AIx) using an oscillometric method were
      measured. Carotid IMT and left ventricular systolic and diastolic function were
      determined by ultrasonography. Clinical status, laboratory parameters (glucose
      and lipid metabolism), and markers of disease activity were also recorded.
      RESULTS: In patients with HIV infection PWV was increased when compared to
      controls (p=0.02), but there were not significant differences in carotid IMT (p=
      0.17). There were no differences for classical risk factors between HIV infected
      patients and controls with the exception of triglycerides level (p<0.001). HIV
      infected patients had a significant reduction in E/A ratio when compared to
      controls (p= 0.03). Significant differences were found for age (p=0.001), PWV
      (0.002) and carotid IMT (p=0.02) between patients with and without left
      ventricular diastolic dysfunction (LVDD). In multiple regression analyze only PWV
      remained correlated with LVDD (OR = 2.90, 95%CI: 1.41-5.97, p=0.004).
      CONCLUSIONS: In patients with HIV infection, without overt cardiovascular
      disease, arterial stiffness was increased. This finding is correlated with
      markers of LVDD. Increased arterial stiffness may be one of the mechanisms
      implicated in the alteration of left ventricular diastolic function in HIV
      infected patients.

PMID- 22396934
TI  - Endosonographic assessment of rectal cancer after neoadjuvant radiotherapy.
AB  - AIM: To assess the changes in the angiogenic status of rectal cancer before and
      after preoperative radiotherapy (RT) using endosonography (ES). MATERIAL AND
      METHODS: Fifty-four patients with rectal cancer were examined by ES before and 6
      7 weeks after preoperative RT and . The tumour size, stage, echostructure and
      vascularization before and after RT were compared. Tumour vascularization was
      determined by qualitative power Doppler and by computer-assisted method. RESULTS:
      Compared to the histological data, ES restaging after RT was accurate in 65% of
      the cases for the T parameter and in 83% for the N parameter (TNM tumour
      classification). The histological data compared with the initial ES examination
      revealed downstaging in relation to the T parameter in 33% and for the N stage in
      24% of the cases. The tumour structure following RT became hyperechogenic in 89%
      of tumours and remained hypoechogenic in 11% of tumours. Power Doppler found a
      reduction in tumour vascularization after RT in 61% of the tumours. The PDVI
      before RT was 10.7+/-5.8% and 6.3+/-4.6% after RT (r<0.05). A strong correlation
      between the qualitative assessment of the vascularization and PDVI was found
      (r=0.536, p<0.001). The vascularization reduction after RT was found to be a
      protective factor which decreased the death risk by about 86 % (OR=0.14,
      r=0.001). CONCLUSIONS: Endorectal Doppler sonographic findings are promising in
      the evaluation of tumour vascularization in patients with rectal cancer. The
      qualitative and quantitative digital assessment of the vascularization gives
      supplementary information about the patients' prognosis.

PMID- 22396935
TI  - The diagnostic efficiency of ultrasound in characterization for thyroid nodules:
      how many criteria are required to predict malignancy?
AB  - OBJECTIVE: The purpose of this study was to define the criteria for use in
      differentiating benign and malignant nodules with the help of the receiver
      operating characteristic analysis and to increase the objective diagnostic
      accuracy of ultrasonography. MATERIALS AND METHODS: A total of 363 patients (307
      women, 56 men) with 363 nodules (22 malignant and 341 benign nodules) were
      included in the study. The presence and absence of each US feature of the
      evaluated nodule - shape taller than wide, irregular margin, hypoechogenicity,
      microcalcification, and intranodular vascularity - were scored 1 and 0,
      respectively. The total ultrasound score was obtained by the summing up of each
      positive ultrasound findings for malignancy. The effect of the total US score in
      the discrimination of benign and malignant nodules was analysed using ROC
      analysis. RESULTS: The cut off values of US score at maximum sensitivity and
      specificity for nodules larger and smaller than one centimeter were two (Az:
      0.783) and three (Az: 0.935), respectively. For nodules greater than one
      centimeter, the calculated diagnostic performances including sensitivity,
      specificity, positive predictive value and negative predictive value, and
      accuracy were 62.5%, 91.5%, 30.3%, 97.7%, and 89,9%, respectively. For nodules
      smaller or equal to one centimeter; the sensitivity, specificity, positive
      predictive value, negative predictive value and accuracy were 83.3%, 94.9%,
      62.5%, 98.2% and 93.8%, respectively. CONCLUSION: Using ultraound, thyroid
      nodules can be characterized effectively. The number of the US features used in
      this distinction varies in respect to the nodule size.

PMID- 22396936
TI  - Development of a methodology for structured reporting of information in
      echocardiography.
AB  - In order to conduct research relying on ultrasound images, it is necessary to
      access a large number of relevant cases represented by images and their
      interpretation. DICOM standard defines the structured reporting information
      object. Templates are tree-like structures which offer structural guidance in
      report construction. AIMS: Laying the foundations of a structured reporting
      methodology in echocardiography, through the generation of a consistent set of
      DICOM templates. MATERIAL AND METHODS: We developed an information system with
      the ability of managing echocardiographic images and structured reports. In order
      to perform a complete description of the cardiac structures, we used 1900 coded
      concepts organized into 344 contexts by their semantic meaning in a variety of
      cardiac diseases. RESULTS: We developed 30 templates, with up to 10 nesting
      levels. The list of templates has a pyramid-like architecture. Two templates are
      used for reporting every measurement and description: "EchoMeasurement" and
      "EchoDescription". Intermediate level templates specify how to report the
      features of echoDoppler findings: "Spectral Curve", "Color Jet", "Intracardiac
      mass". Templates for every cardiovascular structure include the previous ones.
      "Echocardiography Procedure Report" includes all other templates. The templates
      were tested in reporting echo features of 100 patients by analyzing 500 DICOM
      images. CONCLUSIONS: The benefits of these templates has been proven during the
      testing process, through the quality of the echocardiography report, the ability
      to argue and to link every diagnostic feature to a defining image and by opening
      up opportunities for education, research. In the future, our template-based
      reporting methodology might be extended to other imaging modalities.

PMID- 22396937
TI  - Ultrasound of the ankle and foot in rheumatology.
AB  - In the last years musculoskeletal ultrasound (US) has become a very useful
      imaging tool for the evaluation of rheumatic patients and a natural extension of
      the clinical examination of the ankle and foot. Musculoskeletal US allows the
      evaluation of the symptomatic and asymptomatic ankle and foot with a detailed
      analysis of a wide range of elementary lesions at the level of different
      anatomical structures and their distribution in early or long standing disease.
      In inflammatory pathology, it helps in the assessment of the disease activity and
      severity at the joint, tendon or entheseal level and in the detection of
      subclinical pathological features in early disease or residual activity after
      therapy. Moreover, US guided procedures allow accurate diagnostic and therapeutic
      interventions. It is a valuable imaging method that can be also used in the
      follow up of the treated patients (systemic and/ or local therapies or surgical
      procedures), being a patient friendly,  non-invasive, and quick to perform
      method. The aim of this paper is to review the US technique of scanning and the
      indications of US in the analysis of the ankle and foot in rheumatic diseases.

PMID- 22396938
TI  - Ultrasound of the hand and wrist in rheumatology.
AB  - Musculoskeletal Ultrasonography (US) is nowadays widely used for clinical grounds
      and for research purposes in rheumatology. US of the hand and wrist has recently
      developed due to the technological improvement and use of new, high resolution
      transducers. US is currently improving clinical examination of the rheumatic hand
      and wrist and it is commonly used as daily practice by many rheumatologists. The
      number of publications addressing this area of US scanning has grown
      exponentially over the last few years. The aim of this paper is to review the
      current literature on US of the hand and wrist in rheumatology, including US
      scanning techniques, as well as normal and pathological findings.

PMID- 22396939
TI  - From the pseudolipoma to lipoma: staging of the typical radiological appearances.
      Pictorial essay.
AB  - Lipomas are benign mesenchymal tumors, which accounts for 50% of soft tissue
      tumors. Although the etiopathogenesis has not yet been fully understood, it is
      known that lipomas developed at a rate of 1% in the related localizations after
      traumas. Trauma initiates inflammatory reactions in fatty tissue and these can be
      the trigger mechanism for the development of lipomas.  In this pictorial essay 
      the objective was to present the imaging findings associated with the process of
      lipomas development.  "The phases of lipomas formation" was schematized based on
      these data.

PMID- 22396940
TI  - Anomalies of the inferior vena cava in patients with deep venous thrombosis.
      Pictorial essay.
AB  - The incidence of agenesis of inferior vena cava in the general population was
      estimated at 0.6 - 0.8%. In patients with deep vein thrombosis the frequency of
      agenesis was estimated between 5 and 6.7% in young people. In this pictorial
      essay, we present the ultrasound findings obtained in 8 patients with high deep
      venous thrombosis and inferior vena cava anomaly (absence of a segment), compared
      with images obtained by angio-computed tomography or magnetic resonance imaging.
      At the end we discuss the place of abdominal ultrasound in the evaluation of
      these patients.

PMID- 22396941
TI  - Ultrasound assessment of cutaneous/subcutaneous dystrophies in insulin-treated
      patients.  A report on two cases.
AB  - Insulin treatment can lead to local soft tissue dystrophies. We present the cases
      of two insulin-treated subjects with two different injecting systems: a
      basal/bolus and a continuous subcutaneous insulin infusion (insulin pump). The
      local cutaneous/subcutaneous dystrophies adversely affected their glycaemic
      values. A conventional and a high resolution ultrasound (20MHz Dermascan) were
      used to analyze cutaneous and subcutaneous dystrophies. The particularities of
      these cases were the presence of the cutaneous damages, irrespective of the
      insulin treatment system or injected layer and the absence of remission, even
      after 12 months of avoiding the subjected areas.

PMID- 22396942
TI  - Wandering spleen in a child with symptoms of acute abdomen: ultrasonographic
      diagnosis. Case report.
AB  - We report the initial and follow-up ultrasonography (US) findings in a pediatric
      case of wandering spleen with symptoms of acute abdomen, as a rare entity. A four
      year-old boy was referred with complaints of blunt abdominal pain, vomiting and
      fatigue. US detected an oval- shaped, mildly enlarged spleen with inferomedial
      displacement. In right lateral decubitus, the spleen showed further medial
      displacement. Five months later, control US revealed further enlargement of the
      displaced spleen. Seven months later, due to acute torsion of the spleen,
      splenectomy was performed.

PMID- 22396943
TI  - Milwaukee shoulder syndrome associated with pigmented villonodular synovitis.
      Case report.
AB  - Milwaukee shoulder syndrome (MSS) describes a destructive shoulder arthropathy
      associated with of calcium hydroxyapatite and calcium pyrophosphate dihydrate
      crystals deposition found mainly in elderly women. Pigmented villonodular
      synovitis (PVNS) is a benign proliferative disorder of the synovium usually seen
      in young adults, found frequently in the knee joint. We present the case of a 63
      year old Caucasian woman admitted for severe swelling of the left shoulder and
      mild pain, with 10 years history. Clinical signs, laboratory tests, imaging
      studies, and histopathological examinations established the diagnosis of MSS
      associated with PVNS. Surgical partial synoviectomy followed by radiotherapy
      (total dose 36 Gy) was considered with local improvement. This is the first
      report in literature about this association.

PMID- 22396944
TI  - Multiple renal infarctions due to thromboembolism. Importance of ultrasound in
      diagnosis. Case report.
AB  - We present the case of a woman with known risk factors for embolism with multiple
      kidney infarctions. She was admitted with left renal colic, discrete hematuria
      and subfebrility. She was under acenocumarolum treatment but without efficient
      anticoagulation. Ultrasound performed at the emergency room revealed smaller
      right kidney (congenital hypoplasia) and moderately enlarged left kidney with
      hypoechoic areas in the parenchyma. Computer tomography scan with contrast agent
      revealed multiple avascular areas within the left kidney. Evolution was favorable
      after efficient anticoagulation. Contrast enhanced ultrasound performed two weeks
      later revealed only one residual avascular area.  Differential diagnosis was made
      with acute pyelonephritis, cholesterol embolism and acute tubular necrosis in a
      diabetic patient.

PMID- 22396945
TI  - Ultrasound examination of the femoral and popliteal arteries.

PMID- 22396946
TI  - Cystic tumor of the liver.

PMID- 22396947
TI  - University of Medicine and Pharmacy "Victor Babes" Timisoara, Romania. ABC in
      ultrasonography-ultrasound for the students.

PMID- 22396948
TI  - Candida "psilosis"--electromigration techniques and MALDI-TOF mass spectrometry
      for phenotypical discrimination.
AB  - Biofilm-positive strains of Candida parapsilosis are the second most common
      yeasts responsible for bloodstream infections. This pathogen is difficult to
      identify by standard methods from other phenotypically indistinguishable species,
      biofilm-negative Candida orthopsilosis and biofilm-positive Candida metapsilosis.
      From a medical point of view, important information is especially whether the
      strains form biofilm. The biofilm formation enables yeast to colonize artificial
      surfaces thereby protecting the yeast cell against antifungal agents. The
      commonly used genotypic methods including different modifications of the
      polymerase chain reaction have some disadvantages. Therefore, a rapid and
      reliable method able to identify phenotypically indistinguishable C. "psilosis"
      species is still of great interest. In this study, the four well-established
      analytical techniques: gel isoelectric focusing, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, two-dimensional gel electrophoresis and
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry,
      were applied in order to discriminate C. "psilosis" species. The ability of these
      techniques to differentiate between biofilm-positive and biofilm-negative strains
      was further investigated. Our results have revealed that the proposed methods,
      especially matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry of intact yeast cells, can be used as the efficient tools for
      discrimination and identification of the phenotypically indistinguishable
      microorganisms.

PMID- 22396949
TI  - Simultaneous detection of ultratrace lead and copper with gold nanoparticles
      patterned on carbon nanotube thin film.
AB  - Highly sensitive detection of a Pb(2+)-Cu(2+) mixture using gold nanoparticles
      patterned on single-walled carbon nanotube (AuNP-SWCNT) film is reported. The
      gold nanoparticles were deposited electrochemically on carbon nanotube film using
      a cyclic voltammetry technique. The film showed a homogeneous size and density
      that could be easily controlled by the potential scanning cycle and gold
      precursor concentration. Square wave stripping voltammetry (SWSV) was applied to
      the simultaneous detection of Pb(2+) and Cu(2+) under optimized conditions. The
      AuNP-SWCNT electrode exhibited a high increase in sensitivity with a limit of
      detection of 0.546 ppb (R(2) = 0.984) and 0.613 ppb (R(2) = 0.991) for Pb(2+) and
      Cu(2+) ions, respectively, in a mixture of Pb(2+)-Cu(2+) solution (S/N = 3, n =
      5), and a good linear response in the range from 3.31 ppb to 22.29 ppb. The
      electrode exhibited high reproducibility in repetitive measurements with a
      relative standard deviation as low as 4.2% and 2.6% for Pb(2+) and Cu(2+) ions,
      respectively. An interference study showed that Sb(3+), As(3+), Zn(2+), Ca(2+),
      and Na(+) ions did not have a significant effect. This study demonstrated an
      alternative approach to the rapid and reliable detection of heavy metals of
      environmental interest.

PMID- 22396950
TI  - Organic isocyanide-adsorbed gold nanostructure: a SERS sensory device for
      indirect peak-shift detection of volatile organic compounds.
AB  - Organic isocyanide adsorbed on a noble metal nanostructure can be used as a
      platform for a volatile organic compound (VOC) sensor operating via surface
      enhanced Raman scattering (SERS). This is possible since the NC stretching band
      of organic isocyanides such as 2,6-dimethylphenylisocyanide (2,6-DMPI) is very
      susceptible to the surface potential of Au onto which 2,6-DMPI is assembled. The
      surface potential of Au nanoparticles is even subject to change by VOCs, which
      can be easily monitored by the SERS of 2,6-DMPI. Thereby, under the flow of
      CCl(4) vapor at a partial pressure of 12.8 kPa, for instance, the NC stretching
      band is blue-shifted by up to 20 cm(-1) within 30 s, corresponding to a potential
      change of +0.56 V. Conversely, under the flow of butylamine at 12.8 kPa, the NC
      stretching band is red-shifted, instead of being blue-shifted, by as much as 12
      cm(-1). At lower partial pressures, even a blue- or red-shift of 1 cm(-1) was
      reproducibly measured at a partial pressure of 125 mPa, corresponding to 6.5 ppm
      for CCl(4), suggesting that the present detection limit is superior to the
      results obtained via other techniques, especially those operating based on gold
      nanoparticles and aggregates.

PMID- 22396951
TI  - A hydrophobic entrance enhances ion current rectification and induces dewetting
      in asymmetric nanopores.
AB  - Hydrophobic interactions and local dewetting of hydrophobic cavities have been
      identified as a key mechanism for ionic gating in biological voltage-gated
      channels in a cell membrane. Hydrophobic interactions are responsible for
      rectification of the channels, i.e. the ability to transport ions more
      efficiently in one direction compared to the other. We designed single polymer
      nanopores with a hydrophobic gate on one side in the form of a single layer of
      C10 or C18 thiols. This nanoporous system behaves like an ionic diode whose
      direction of rectification is regulated by the pH of the electrolyte. In
      addition, reversible dewetting of the hydrophobic region of the pore was observed
      as voltage-dependent ion current fluctuations in time between conducting and non
      conducting states. The observations are in accordance with earlier molecular
      dynamics simulations, which predicted the possibility of spontaneous and
      reversible dewetting of hydrophobic pores.

PMID- 22396952
TI  - Quantum dot enabled detection of Escherichia coli using a cell-phone.
AB  - We report a cell-phone based Escherichia coli (E. coli) detection platform for
      screening of liquid samples. In this compact and cost-effective design attached
      to a cell-phone, we utilize anti-E. coli O157:H7 antibody functionalized glass
      capillaries as solid substrates to perform a quantum dot based sandwich assay for
      specific detection of E. coli O157:H7 in liquid samples. Using battery-powered
      inexpensive light-emitting-diodes (LEDs) we excite/pump these labelled E. coli
      particles captured on the capillary surface, where the emission from the quantum
      dots is then imaged using the cell-phone camera unit through an additional lens
      that is inserted between the capillary and the cell-phone. By quantifying the
      fluorescent light emission from each capillary tube, the concentration of E. coli
      in the sample is determined. We experimentally confirmed the detection limit of
      this cell-phone based fluorescent imaging and sensing platform as ~5 to 10 cfu
      mL(-1) in buffer solution. We also tested the specificity of this E. coli
      detection platform by spiking samples with different species (e.g., Salmonella)
      to confirm that non-specific binding/detection is negligible. We further
      demonstrated the proof-of-concept of our approach in a complex food matrix, e.g.,
      fat-free milk, where a similar detection limit of ~5 to 10 cfu mL(-1) was
      achieved despite challenges associated with the density of proteins that exist in
      milk. Our results reveal the promising potential of this cell-phone enabled field
      portable and cost-effective E. coli detection platform for e.g., screening of
      water and food samples even in resource limited environments. The presented
      platform can also be applicable to other pathogens of interest through the use of
      different antibodies.

PMID- 22396953
TI  - Synthesis of novel ZnS nanocages utilizing ZIF-8 polyhedral template.
AB  - Truncated rhombic dodecahedral zeolitic imidazolate framework-8 (ZIF-8)
      nanocrystals are fabricated with acetate as a modulating ligand; ZnS hollow
      polyhedra with uniform morphology are obtained using the ZIF-8 templates.

PMID- 22396954
TI  - Translocation-coupled transmetalation at the origin of a dinuclear lead porphyrin
      complex: implication of a hanging-atop coordination mode.
AB  - Translocation of a lead cation from the N-core of a porphyrin to a hanging
      carboxylate group is coupled to a transmetalation process with a second lead
      cation, leading to a dinuclear species. A novel hanging-atop coordination mode is
      responsible for the dynamic and stereocontrolled binding of lead to the porphyrin
      core.

PMID- 22396955
TI  - A general stereoselective enamine mediated alkylation of alpha-substituted
      aldehydes.
AB  - We herein present a general enamine-mediated alpha-alkylation of alpha
      substituted aldehydes with carbenium ions for the stereoselective construction of
      quaternary stereogenic centers.

PMID- 22396956
TI  - Excitonic coupling interactions in the self-assembly of perylene-bridged bis(beta
      cyclodextrin)s and porphyrin.
AB  - A supramolecular self-assembly has been constructed by perylene-bridged bis(beta
      cyclodextrin)s with water-soluble porphyrin through hydrophobic interactions,
      showing strong excitonic coupling interactions between perylene backbones and
      included porphyrins.

PMID- 22396957
TI  - [Radioactivity: curse and blessing].

PMID- 22396958
TI  - [Could the VAD protocol be the first line therapy for multiple myeloma in
      subSaharan Africa? The Brazzaville experience].

PMID- 22396959
TI  - [Sickle cell disease is one century old: what about therapeutics?].

PMID- 22396961
TI  - All things being equal.

PMID- 22396960
TI  - The therapeutic misconception, decision making and informed  consent: the ethics
      of trial participation for neuromuscular  disorders.

PMID- 22396962
TI  - The author file: Susan Cox.

PMID- 22396963
TI  - Points of view: Networks.

PMID- 22396964
TI  - Fatherless stem cells.

PMID- 22396965
TI  - A microscopic endoscope.

PMID- 22396966
TI  - High-resolution chromatin immunoprecipitation.

PMID- 22396967
TI  - Timing an intron's departure.

PMID- 22396968
TI  - Optimal stoichiometry for pluripotency.

PMID- 22396969
TI  - Better resolution for structured-illumination microscopy.

PMID- 22396970
TI  - Bearing the mark.

PMID- 22396971
TI  - Treatment of neovascular glaucoma after proton therapy for uveal melanomas with
      ranibizumab injection: preliminary results.

PMID- 22396972
TI  - Porcelain aorta, left arterio-venous fistula and critical ostial coronary artery
      disease.

PMID- 22396973
TI  - [Fully covered self expandable metal stent for the treatment of benign biliary
      strictures].

PMID- 22396974
TI  - The integration of emotional availability into a developmental  psychopathology
      framework: reflections on the Special Section  and future directions.

PMID- 22396975
TI  - Sean Morrison and the Texas brain gain.

PMID- 22396976
TI  - Eyes on Medicare program's house calls for comorbid patients.

PMID- 22396977
TI  - Full-rotation three-dimensional intraoperative imaging during spinal procedures.
      A summary of ECRI Institute's Emerging Technology Evidence Report.

PMID- 22396978
TI  - Primary care continues to feel the strain.

PMID- 22396979
TI  - You are not alone, clinical executive.

PMID- 22396980
TI  - Copayment, coinsurance rates change little.

PMID- 22396981
TI  - Wellness programs grow to meet challenge.

PMID- 22396982
TI  - Contraception compromise: questions unanswered on how plan will work.

PMID- 22396983
TI  - SGR stalemate: hope fades for long-term solution from Congress.

PMID- 22396984
TI  - Regulation frustration: insurers seek time on simplified plan summaries.

PMID- 22396985
TI  - Largest U.S. military hospitals: ranked by number of staffed total beds.

PMID- 22396986
TI  - 12 for 2012: twelve tips for healthier eating.  It's not about individual
      nutrients anymore.

PMID- 22396987
TI  - Sex and the older woman.  Women over age 50 are having sex--and developing STIs-
      at a higher rate than commonly believed.

PMID- 22396988
TI  - Yoga and stretching are equally effective for easing low back pain.

PMID- 22396989
TI  - Ask the doctor. I have Dupuytren's contracture in both hands. I've had "needle"
      surgery in one hand, and the fingers straightened. But they seem to want to
      contract again. What can I do?

PMID- 22396990
TI  - Ask the doctor.  Ten years ago, I had uterine artery embolization to get rid of
      uterine fibroids.  How long do the plastic particles they inject into the
      arteries stay in the body?  Do they dissolve?

PMID- 22396991
TI  - Ask the doctor.  I'm 64 and have been diagnosed with uveitis in my right eye. 
      What causes it, and what is the best treatment for it?

PMID- 22396992
TI  - Coughing again? It could be COPD.

PMID- 22396993
TI  - FDA approves new melanoma treatments.

PMID- 22396995
TI  - Legionnaires' disease: cause for concern?

PMID- 22396994
TI  - Should you be tested for prostate cancer?  PSA testing comes under scrutiny by
      the U.S. Prevention Services Task Force.

PMID- 22396996
TI  - Dialysis patients: how to plan for a disaster.

PMID- 22396997
TI  - What should I know about Lupron Depot for treating prostate cancer?

PMID- 22396998
TI  - I was recently diagnosed with mitral valve stenosis.  Will it improve through
      exercise and diet?  I have no symptoms.

PMID- 22396999
TI  - Vitamin & mineral supplements: healthy or harmful?

PMID- 22397000
TI  - Take action to banish bunion pain.

PMID- 22397001
TI  - 5 steps to lower your risk of diabetes.

PMID- 22397002
TI  - Do you still need a Pap test?

PMID- 22397003
TI  - Got arthritis? Get active!

PMID- 22397004
TI  - Will ginkgo biloba keep me from developing dementia?

PMID- 22397005
TI  - Does bipolar disorder run in families?

PMID- 22397006
TI  - What's the difference between wet and dry macular degeneration?

PMID- 22397007
TI  - New insight into rheumatoid arthritis management. The disease and the drugs used
      to treat it have been linked to cardiovascular disease, melanoma, and fracture.

PMID- 22397008
TI  - New focus on raising HDL "good" cholesterol. But the value of this is not
      entirely clear.

PMID- 22397009
TI  - Inflammatory bowel diseases: advances in treatment, causes. Probiotics may be a
      major weapon in the arsenal against these chronic intestinal diseases.

PMID- 22397010
TI  - A good night's sleep and morning exercise may protect against dementia.  Changes
      in the sleep-wake cycle interfere with brain function.

PMID- 22397011
TI  - Mediterranean diet helps stave off chronic disease and disorders. Increasing
      evidence points to its benefits, which include protection against vascular events
      and inflammation.

PMID- 22397012
TI  - Before I consider knee surgery for my osteoarthritis (OA), is there anything I
      can do to reduce pain and avoid surgery?

PMID- 22397013
TI  - News of the negative effects of taking dietary supplements has been in the
      headlines. What are the possible dangers from taking dietary supplements?

PMID- 22397014
TI  - Much has been made of prostate cancer screening recently.  What are the pros and
      cons of screening for this disease?

PMID- 22397015
TI  - [Homage to Professor Pierre Delvoye].

PMID- 22397016
TI  - Kidney stones: common, painful, preventable.

PMID- 22397017
TI  - Big thighs may be wise.

PMID- 22397018
TI  - Worried about warts?

PMID- 22397019
TI  - On call. I am 72 years old and in good health. I've had left knee pain on and off
      for almost six months, nothing too severe, but it aches if I walk more than a
      mile or so, and I sometimes get sharp pain on the stairs. My doctor sent me for
      an MRI of both knees; it showed "mild to moderate osteoarthritis" in both knees
      and a torn meniscus in my right knee, which feels fine. I think I know what to do
      about my painful knee--but what should I do for the torn meniscus in my "good"
      knee?

PMID- 22397020
TI  - [Mental training: learning through motor imagery and imitation].

PMID- 22397021
TI  - Study compares iTRAQ and mTRAQ labeling techniques in global proteomics.

PMID- 22397022
TI  - Gene fusion implicated in lung cancer occurrence.

PMID- 22397024
TI  - New database search tool hopes to provide improved accuracy and sensitivity for
      automated identification of peptides.

PMID- 22397023
TI  - ISG15 implicated in cytoskeleton disruption and promotion of breast cancer.

PMID- 22397025
TI  - How to manage a school-work-life balance.

PMID- 22397026
TI  - [The physician-writer Silas Weir Mitchell and the plantom phenomenon].

PMID- 22397027
TI  - Metabolic markers in sports medicine.
AB  - Physical exercise induces adaptations in metabolism considered beneficial for
      health. Athletic performance is linked to adaptations, training, and correct
      nutrition in individuals with genetic traits that can facilitate such
      adaptations. Intense and continuous exercise, training, and competitions,
      however, can induce changes in the serum concentrations of numerous laboratory
      parameters. When these modifications, especially elevated laboratory levels,
      result outside the reference range, further examinations are ordered or
      participation in training and competition is discontinued or sports practice
      loses its appeal. In order to correctly interpret commonly used laboratory data,
      laboratory professionals and sport physicians need to know the behavior of
      laboratory parameters during and after practice and competition. We reviewed the
      literature on liver, kidney, muscle, heart, energy, and bone parameters in
      athletes with a view to increase the knowledge about clinical chemistry applied
      to sport and to stimulate studies in this field. In liver metabolism, the
      interpretation of serum aminotransferases concentration in athletes should
      consider the release of aspartate aminotransferase (AST) from muscle and of
      alanine aminotransferase (ALT) mainly from the liver, when bilirubin can be
      elevated because of continuous hemolysis, which is typical of exercise. Muscle
      metabolism parameters such as creatine kinase (CK) are typically increased after
      exercise. This parameter can be used to interpret the physiological release of CK
      from muscle, its altered release due to rhabdomyolysis, or incomplete recovery
      due to overreaching or trauma. Cardiac markers are released during exercise, and
      especially endurance training. Increases in these markers should not simply be
      interpreted as a signal of cardiac damage or wall stress but rather as a sign of
      regulation of myocardial adaptation. Renal function can be followed in athletes
      by measuring serum creatinine concentration, but it should be interpreted
      considering the athlete's body-mass index (BMI) and phase of the competitive
      season; use of cystatin C could be a reliable alternative to creatinine. Exercise
      and training induce adaptations in glucose metabolism which improve glucose
      utilization in athletes and are beneficial for reducing insulin insensitivity in
      nonathletes. Glucose metabolism differs slightly for different sports
      disciplines, as revealed in laboratory levels. Sport activities induce a blood
      lipid profile superior to that of sedentary subjects. There are few reports for a
      definitive conclusion, however. The differences between athletes and sedentary
      subjects are mainly due to high-density lipoprotein cholesterol (HDLC)
      concentrations in physically active individuals, although some differences among
      sport disciplines exist. The effect of sports on serum and urinary markers for
      bone metabolism is not univocal; further studies are needed to establish the real
      and effective influence of sport on bone turnover and especially to establish its
      beneficial effect.

PMID- 22397028
TI  - Cytokines in diabetic nephropathy.
AB  - Diabetic nephropathy (DN), the most common cause of end-stage renal disease
      (ESRD), is increasingly considered an inflammatory process characterized by
      leukocyte infiltration at every stage of renal involvement. Cytokines act as
      pleiotropic polypeptides that regulate inflammatory and immune responses,
      providing important signals in the pathologic and physiologic processes.
      Inflammation and activation of the immune system are closely involved in the
      pathogenesis of diabetes and its microvascular complications. Proinflammatory,
      Th1, Th2, and Th17 cytokines, as well as TGF-beta, all take part in the
      development and progression of DN. Gene polymorphism of cytokines and their
      receptors may have functional variations and can be applied to predict the
      susceptibility and progression to DN. Improved knowledge on recognizing cytokines
      as significant pathogenic mediators in DN leaves opens the possibility of new
      potential therapeutic agents for future clinical treatments.

PMID- 22397029
TI  - Advances in antibiotic measurement.
AB  - Antibiotics are most commonly prescribed drugs in clinical practice. Therapeutic
      drug monitoring of these medications is typically associated with a select group
      of antibiotics such as aminoglycosides and vancomycin. Outside this group, other
      antibiotics such as chloramphenicol and antituberculosis agents may also require
      monitoring. Due to their wide therapeutic index, other classes of antibiotics
      such as penicillins, cephalosporin, sulfonamides, quinolones, and macrolides do
      not generally require routine therapeutic drug monitoring. Determination of serum
      or plasma concentration of these drugs, however, may be beneficial in those
      patients with compromised renal function. As can be expected, immunoassays for
      routine monitoring of aminoglycosides and vancomycin have been developed and are
      widely commercially available. Tests for other antibiotics, due to their
      infrequent use and low clinical application, are generally limited to in-house
      developed methods.

PMID- 22397030
TI  - Relevance of the lectin pathway of complement in rheumatic diseases.
AB  - Due to its importance both in the clearance of pathogens that contribute as
      rheumatic etiological agents and in the disposal of apoptotic bodies and
      potential autoimmune initiators, deficiencies of the components of the lectin
      pathway of complement have been found to increase susceptibility and modulate the
      severity of most rheumatic disorders. This chapter introduces the general aspects
      of the structure, function, and genetics of lectin pathway components and
      summarizes current knowledge of the field regarding rheumatic diseases
      predisposition and modulation.

PMID- 22397031
TI  - Clusterin in Alzheimer's disease.
AB  - Clusterin, also known as apolipoprotein J, is a ubiquitous multifunctional
      glycoprotein. Following its identification in 1983, clusterin was found to be
      clearly increased in Alzheimer's disease (AD). Later research demonstrated that
      clusterin could bind amyloid-beta (Abeta) peptides and prevent fibril formation,
      a hallmark of AD pathology. In addition to preventing excessive inflammation,
      intracellular clusterin was found to reduce apoptosis and oxidative stress.
      Although early studies were inconclusive, two recent large-scale genome-wide
      association studies (GWAS) independently identified variants within the clusterin
      gene as risk factors for developing AD. This review focuses on the
      characteristics of clusterin and possible mechanisms of its relationship to AD.

PMID- 22397032
TI  - Fetuin-A and the cardiovascular system.
AB  - Fetuin was first isolated from bovine serum in 1944. It is now most commonly
      known as either fetuin-A or alpha-2-HS-glycoprotein (AHSG), the protein product
      of Ahsg gene. A prominent feature of this protein is the functional diversity
      exerted in human physiology and pathophysiology. Fetuin-A plays a role in bone
      metabolism, metabolic disorders such as insulin resistance and diabetes mellitus
      (DM), and central nervous system (CNS) disorders such as ischemic stroke (IS) and
      neurodegenerative diseases. In addition, emerging evidence suggests involvement
      of fetuin-A in the cardiovascular system. However, there are many discordant
      findings on the associations between fetuin-A and vascular diseases. In other
      words, it is unknown whether fetuin-A is an exacerbating or a protective factor
      in the cardiovascular system. One reason for the seemingly inconsistent behavior
      is the dual functionality of fetuin-A in vascular diseases where it can act as an
      atherogenic factor or as a vascular calcification inhibitor. In addition, the
      existence of confounding factors such as DM and renal dysfunction can veil the
      primary association between fetuin-A and clinical parameters. Considering these
      issues, we discuss the role of fetuin-A for atherosclerosis and vascular
      calcification in this review.

PMID- 22397033
TI  - Genetic and clinical aspects of Brugada syndrome: an update.
AB  - The Brugada Syndrome (BS) is a "channellopathy," characterized by ion (e.g.,
      sodium, calcium, and potassium) channel dysfunction and typical ECG alterations,
      originally described by Osher and Wolff in 1953 and further elucidated by Josep
      and Pedro Brugada in 1991. BS is typically associated with a high risk for sudden
      cardiac death (SCD) in young and otherwise healthy adults. Although in several
      patients the heart is structurally normal, subtle structural abnormalities in the
      right ventricular outflow tract are increasingly been reported. The worldwide
      prevalence of this disorder is still uncertain, and there are some significant
      regional differences. The syndrome is characterized by a strong genetic basis,
      and several mutations have been identified in genes encoding subunits of cardiac
      sodium, potassium, and calcium channels, as well as in genes involved in the
      trafficking or regulation of these channels. Accordingly, eight types of BS (from
      BS1 to BS8) have already been described, involving mutations in SCN5A, GPD1-L,
      CACNA1c, CACNB2b, SCN1B, KCNE3, SCN3B, and HCN4 genes. The vast majority (i.e.,
      up to two-third) of BS patients is asymptomatic, whereas the leading clinical
      manifestation is polymorphic ventricular tachycardia that can degenerate into
      ventricular fibrillation (VF) and SCD. The diagnosis is still challenging, and
      ECG abnormalities represent one component of the diagnostic criteria which also
      include clinical and demographic data. Although molecular genetic testing is
      effective in detecting mutations in 20-38% of BS patients, it represents an
      appealing option for stratifying the risk of adverse events as well as for
      prenatal testing.

PMID- 22397034
TI  - Varying clinical features of Turkish Kawasaki disease patients.
AB  - Kawasaki disease (KD) is an acute, systemic and self-limited vasculitis that is
      complicated with the development of coronary artery (CA) aneurysms. We present
      the clinical features of Turkish KD patients from a tertiary referral center.
      When 33 KD patients were assessed, a number of features stood out as differing
      from the expected, for example, periungual peeling 7.5 +/- 7.5 days after fever
      onset--42.4% of patients had periungual peeling within 14 days after fever onset.
      CA involvement was detected at an average of 12.3 +/- 7.9 days after fever onset.
      Fifty percent of the patients had been diagnosed to have CA involvement within
      eight days after the onset of fever. The performance of criteria suggested by
      American Heart Association was satisfactory, with 19 of 29 patients (65.5%)
      having three or more of the required laboratory features (sensitivity 65.5%). We
      believe Turkish patients may present differences in the course of KD.

PMID- 22397035
TI  - The classification and differential diagnosis of absence seizures with short-term
      video-EEG monitoring during childhood.
AB  - Absence seizures are idiopathic epilepsies characterized by impairment of
      consciousness and generalized 2.5-4 Hz spike and slow wave discharges. This
      prospective study was performed to classify and define properties of subgroups of
      absence epilepsies. We included 31 patients, of whom seven were in the
      differential diagnosis group. On admission, absence epilepsy provisional
      diagnosis was considered in 16 patients clinically and in the other 15 patients
      based on routine EEG findings. Ictal EEGs were recorded by video-EEG monitoring
      in 23 of the patients (totally 202 ictal recordings). Patients were diagnosed as
      childhood absence epilepsy (n=8), juvenile absence epilepsy (n=10), juvenile
      myoclonic epilepsy (n=3), eyelid myoclonia with absences (n=2), and perioral
      myoclonia with absences (n=1). Neuroimaging, video-EEG monitoring and especially
      ictal recordings are important for classification of epilepsies in addition to
      history, physical examination and routine EEG findings. Video-EEG monitoring is
      required to classify, to make differential diagnosis and to determine the
      treatment plan and prognosis.

PMID- 22397036
TI  - Seroprevalence of Bordetella pertussis immunoglobulin G antibodies among children
      in Samsun, Turkey.
AB  - In this study, we aimed to investigate anti-pertussis immunoglobulin (Ig) G
      antibodies in the serum of children in our region vaccinated against pertussis
      with four doses. Between August 2008-2009, antibody levels to Bordetella
      pertussis (B. pertussis) antigens were studied in 385 serum samples from healthy
      children aged 1.5-18 years (y) vaccinated against pertussis in Samsun, Turkey.
      The study population was divided into six groups according to ages: 1.5-3 y; 4-5
      y; 6-8 y; 10-12 y; 13-15 y; and 16-18 y. IgG antibodies to B. pertussis antigens
      were measured with a commercial ELISA kit. Mean age of the children was 9.6 +/-
      5.3 y. Anti-pertussis IgG titers were positive in 48.3% of the cases. The lowest
      positivity rate was determined in the 4-5 y age group (28.1%) and the highest
      rate in the 16-18 y age group (64.2%). Geometric mean titer of anti-pertussis
      antibodies was 39.2 IU/ml, and again the lowest value was obtained in the 4-5 y
      age group (23.3 IU/ml) and the highest in the 16-18 y age group (51.4 IU/ml). The
      antibody levels to B. pertussis antigens significantly decrease 4-6 years after
      vaccination and again increase in school children, possibly due to natural
      infection.

PMID- 22397037
TI  - Leptin receptor gene Gln223Arg polymorphism is not associated with obesity and
      metabolic syndrome in Turkish children.
AB  - The aim of the study was to investigate the relationship between leptin receptor
      gene (LEPR) Gln223Arg polymorphism and obesity in Turkish children. Ninety-two
      obese and 99 lean children (between 5-15 years) were included in the study.
      Twenty-three of the obese children were diagnosed with metabolic syndrome. Blood
      samples were collected for morning fasting blood glucose, insulin, leptin, and
      lipid level measurements. LEPR Gln223Arg polymorphism was analyzed by restriction
      fragment length polymorphism. Significant differences were observed in
      anthropometric measurements, fasting blood glucose, insulin, leptin, and lipid
      levels between obese and lean children. Serum leptin levels were markedly higher
      in obese children. No significant association was noted between Gln223Arg
      polymorphism and serum leptin, insulin and lipid levels. There were no
      differences in the genotype frequencies or allele distribution for Gln223Arg
      polymorphism among obese, obese with metabolic syndrome and lean children. Our
      findings suggest that there is no association between Gln223Arg polymorphism and
      obesity in Turkish children.

PMID- 22397038
TI  - Oseltamivir use in infants under one year of age: are there still unanswered
      questions?
AB  - The influenza A (H1N1) virus responsible for the 2009 pandemic follows a more
      severe course in children, thus increasing the need for hospitalization. On the
      other hand, during the first weeks of the pandemic, use of oseltamivir (Tamiflu)
      in children was restricted, and it was not yet approved for use in children
      younger than one year of age because of the lack of adequate safety and efficacy
      data and because of concerns regarding central nervous system (CNS) toxicity in
      newborn rats. However, citing a state of emergency, conditional approval was
      granted first in the United States, then Europe and finally in Turkey. The main
      aim of this study was to share our experience with oseltamivir in 35 patients
      less than one year of age during the 2009 H1N1 pandemic. A total of 35 infants
      (21 boys, 14 girls; mean age: 160 days [24-335]) were treated during the study
      period. Six patients required hospitalization, five of whom (14.2%) had an
      underlying chronic disorder. During the pandemic, we diagnosed H1N1 infection
      based on clinical symptoms. Nasal swabs were positive for H1N1 in 88.5% of cases.
      Mild elevations in liver enzymes were present in 39.1% of patients with available
      blood workup at presentation, and no changes in liver enzymes were observed with
      oseltamivir treatment. None of the patients developed any neurological,
      dermatological or gastrointestinal side effects in association with oseltamivir
      treatment. No complaints of drowsiness, lethargy or sleep disturbance were
      reported by the parents. Although our case number is very limited, our study
      results suggest that oseltamivir is well tolerated in young infants, and we can
      conclude that oseltamivir could be used in the treatment of influenza A in this
      age group. Nevertheless, further studies are needed to evaluate using oseltamivir
      in more cases among infancy age groups.

PMID- 22397039
TI  - Evaluation of cases with impaired state of consciousness: Gaziantep Children's
      Hospital experience.
AB  - The aim of this study was to characterize the etiology, course and prognosis in
      children admitted to a pediatric intensive care unit (PICU) of Gaziantep
      Children's Hospital for impaired state of consciousness. Three hundred and eighty
      cases were evaluated. Convulsions (44%; n=170) were the leading cause of the
      impaired state of consciousness followed by poisonings, envenomation, infection,
      metabolic disease, electrical injury, hepatic encephalopathy, intracranial
      hemorrhage, brain tumor, and drowning. The diagnosis was definite in 95% (n=359)
      and probable in 5% (n=21) of cases. Twenty-seven (7%) patients died with impaired
      state of consciousness. We suggest that defining the causes of impaired state of
      consciousness in a specific region will help physicians to evaluate the patients
      faster and in a more systemic manner. Since most of the causes seem to be
      preventable, appropriate education programs and policies should be provided for
      improving sanitation and socioeconomic conditions.

PMID- 22397040
TI  - Hypercalcemia in glycogen storage disease type I patients of Turkish origin.
AB  - Glycogen storage disease type I (GSD I) is an autosomal recessive disorder caused
      by defects in the glucose-6-phosphatase complex. Deficient activity in the
      glucose-6-phosphatase-a (G6Pase) catalytic unit characterizes GSD IA and defects
      in the glucose-6-phosphate transporter protein (G6PC) characterize GSD IB. The
      main clinical characteristics involve fasting hypoglycemia, hyperuricemia,
      hyperlactatemia, and hyperlipidemia. Hypercalcemia arose as an unknown problem in
      GSD I patients, especially in those with insufficient metabolic control. The aim
      of the present study was to obtain the prevalence of hypercalcemia and to draw
      attention to the metabolic complications of GSD I patients, including
      hypercalcemia in poor metabolic control. Hypercalcemia frequency and the
      affecting factors were studied cross-sectionally in 23 GSD I pediatric subjects.
      Clinical diagnosis of GSD I was confirmed in all patients either through
      documentation of deficient G6Pase enzyme activity levels on liver biopsy samples
      or through G6PC gene sequencing of DNA. Hypercalcemia was detected in 78.3% of
      patients with GSD I. Different from the previous report about hypercalcemia in a
      GSD IA patient who had R83H and 341delG mutations, we could not identify any
      genotype-phenotype correlation in our GSD I patients. Hyperlactatemia and
      hypertriglyceridemia correlated significantly with hypercalcemia. Furthermore, no
      differences in serum calcium concentrations could be demonstrated between
      patients with optimal metabolic control. We observed hypercalcemia in our series
      of GSD I patients during acute metabolic decompensation. Therefore, we speculate
      that hypercalcemia should be considered as one of the problems of GSD I patients
      during acute attacks. It may be related with prolonged lactic acidosis or may be
      a pseudohypercalcemia due to hyperlipidemia that can be seen in GSD I patients
      with poor metabolic control.

PMID- 22397041
TI  - A study of growth failure and its related factors in children from 0 to 2 years
      in Tehran, Iran.
AB  - In this study, we aimed to estimate the prevalence of growth failure and identify
      the risk factors for this health problem in infants under two years old in
      Tehran, Iran. Using a cluster sampling method, 2182 infants' health files were
      randomly selected from eight health centers in Tehran. Growth failure was defined
      as a decrease in a child's weight (minimum 50 grams) at each attendance compared
      to the previous evaluation. The prevalence rate was between 0.05% and 6.2% at the
      different measurements. The regression analysis revealed that the presence of
      diarrhea [odds ratio (OR): 4.01, 95% confidence interval (CI): (3.50, 4.60)],
      respiratory infections [OR: 4.95, 95% CI: (4.40, 5.57)] and urinary tract
      infections [OR: 6.35, 95%CI: (3.97, 10.18)], as well as discontinuation of breast
      feeding [OR: 10.91, 95%CI: (7.82, 15.23)], teething [OR: 4.14, 95% CI: (3.61,
      4.75)] and complementary feeding [OR: 9.58, 95% CI: (6.48, 14.18)] were the
      significant risk factors for growth failure. Generally, our study showed a high
      prevalence of growth failure in infants less than two years in Tehran. More
      efforts are needed for promoting the knowledge level of mothers and healthcare
      providers to control this health problem in Iran.

PMID- 22397042
TI  - The prognostic factors in children undergoing pulmonary metastatectomy.
AB  - A retrospective analysis was performed to determine the prognostic factors
      affecting survival in children who underwent pulmonary metastatectomy. Seventeen
      patients who underwent pulmonary metastatectomy between 2000-2006 were evaluated
      retrospectively by means of age, sex, primary diagnosis, time of metastasis
      appearance, number of nodules found on imaging examinations, type of management,
      surgical data, and outcome. Video-assisted thoracoscopic surgery (VATS) was used
      in 11 patients, and all patients underwent thoracotomy consequently. The nodule
      was composed of tumor cells in 13 (76%) patients and had positive surgical
      margins in 5 (38%). The time of metastasis appearance, number of metastases and
      completeness of the nodule excision did not affect survival (p=0.31, p=0.87 and
      p=0.56, respectively). Nodule size >1 cm was associated with dismal survival
      (p=0.008). Time elapsed until the diagnosis of pulmonary metastasis, number of
      metastases and the completeness of metastatectomy do not have an impact on
      survival. The only significant prognostic factor is the size of the largest
      metastatic nodule. The presence of a metastatic nodule >1 cm is associated with a
      worse outcome in pediatric patients. VATS is an adjunct method to thoracotomy in
      the surgical management of pulmonary metastasis in children.

PMID- 22397043
TI  - When do we need to perform a diagnostic lumbar puncture for neurometabolic
      diseases? Positive yield and retrospective analysis from a tertiary center.
AB  - Neurometabolic diseases diagnosed by cerebrospinal fluid (CSF) examination are
      GLUT1 deficiency, serine-deficiency syndromes, glycine encephalopathy, cerebral
      folate deficiency, neonatal vitamin-responsive epileptic encephalopathies,
      disorders of monoamine metabolism, and y-amino butyric acid (GABA) metabolism. We
      retrospectively analyzed and compared the demographic, clinical, laboratory, and
      neuroimaging features of 62 patients in whom CSF examination was performed. Of
      the 62 patients, 16 (25.8%) had a final diagnosis, including succinic
      semialdehyde dehydrogenase (SSADH) deficiency (n=4), aromatic amino acid
      decarboxylase (AADC) deficiency (n=4), L-dopa-responsive dystonia (n=3), glycine
      encephalopathy (n=2), pyridoxal-phosphate-dependent seizures (n=l), cerebral
      folate deficiency (n=1), and serine biosynthesi defect (n=1). Parental
      consanguinity was present in all patients except one Positive yield of a
      diagnostic lumbar puncture (LP) for the diagnosis of inherited neurotransmitter
      metabolism disorder was 25.8% overall. Oculogyric crisis (50%), diurnal variation
      (81.8%) and consanguinity (93.8%) were the only statistically significant
      variables between patients with and without a specific diagnosis. It is
      challenging to diagnose neurotransmitter defects, since there is no ideal set of
      clinical symptoms. In our cohort, consanguinity, diurnal variation and abnormal
      ocular movements were the most significant findings associated with a diagnosis
      of a specific neurometabolic disorder based on CSF examination. Early diagnosis
      is of great importance not only for specific treatment, but also for genetic
      counseling and prenatal diagnosis.

PMID- 22397044
TI  - Successful treatment of multidrug-resistant Escherichia coli bacteremia with
      tigecycline in an acute myeloid leukemia child.
AB  - The multidrug-resistant bacterial infections cause high mortality in
      immunocompromised patients because of the limited antibacterial choices.
      Tigecycline, first member of the glycylcyclines, has in vitro activity against a
      wide variety of organisms, including multidrug-resistant pathogens; however, it
      has not yet been approved for use in children. Herein, we report a nine-year-old
      girl with acute myeloid leukemia who was treated successfully with tigecycline
      due to multidrug-resistant Escherichia coli bacteremia.

PMID- 22397045
TI  - A rare metabolic complication of acute lymphoblastic leukemia in childhood:
      lactic acidosis.
AB  - A 13-year-old boy presented with nausea, fatigue, weight loss, and bone pain for
      two months. Complete blood count and serum renal and liver function tests were
      all normal. Blood gas analysis revealed severe metabolic acidosis with high anion
      gap. Lactate level was 61.2 mmol/L. Abdominal ultrasonography yielded bilateral
      nephromegaly and hepatomegaly with increased echogenicity. Peripheral blood smear
      revealed 2% blasts. Bone marrow aspiration showed 'Common ALL Antigen'-negative
      acute lymphoblastic leukemia by flow cytometric analysis. Metabolic acidosis
      dissolved as soon as chemotherapy was begun. Lactic acidosis at the presentation
      of acute lymphoblastic leukemia--especially with low tumor burden--is a very rare
      and almost always fatal complication. Our patient is still alive and in
      remission, which is a point of interest in this child.

PMID- 22397046
TI  - Sjogren-Larsson syndrome: report of monozygote twins and a case with a novel
      mutation.
AB  - Sjogren-Larsson syndrome is an autosomal recessive neurocutaneous disease caused
      by mutations in the ALDH3A2 gene for fatty aldehyde dehydrogenase, a microsomal
      enzyme that catalyzes the oxidation of medium- and long-chain aliphatic aldehydes
      fatty acids. We studied three Turkish Sjogren-Larsson syndrome patients with
      ichthyosis, developmental delay, spastic diplegia, and brain white matter
      disease. One patient was homozygous for a novel ALDH3A2 mutation in exon 5. The
      mutation involves the codon 228 (CGC) with the transversion G->A modifying the
      codon in CAC, leading to the substitution of the original arginine with a
      histidine (R228H), modifying the stereospecific properties of this region. These
      results add to the understanding of the genetic basis of Sjogren-Larsson syndrome
      and will be useful for DNA diagnosis of this disease.

PMID- 22397047
TI  - Secondary pseudohypoaldosteronism caused by urinary tract infection associated
      with urinary tract anomalies: case reports.
AB  - Secondary pseudohypoaldosteronism type 1 develops due to transient aldosterone
      resistance in renal tubules and is characterized by renal sodium loss,
      hyponatremia, hyperkalemia and high plasma aldosterone levels. Although many
      reasons are described, urinary tract infections and/or urinary tract anomalies
      are the most common causes. Although the cause of the tubular resistance is not
      known exactly, renal scar development due to obstruction and reduced sensitivity
      of mineralocorticoid receptors due to cytokines such as transforming growth
      factor (TGF)-beta are the possible mechanisms. It is seen especially within the
      first three months of life and the frequency decreases with age. The treatment is
      usually elimination of the underlying cause. In this article, we present four
      patients with several urinary tract anomalies and concomitant urinary tract
      infection who developed transient secondary pseudohypoaldosteronism.

PMID- 22397048
TI  - Intrapericardial teratoma in a newborn: a case report.
AB  - We report a successfully surgically intervened case of intrapericardial teratoma,
      which was diagnosed prenatally. Intrapericardial teratomas are rare cases, and
      surgical management of those tumors are challenging in this age group. The
      compression effect of the mass led to misdiagnosis of the anomaly as a
      transposition of the great vessels. We conclude that intrauterine
      echocardiography in experienced hands is an essential tool for the follow-up of
      these patients to detect the pericardial effusion and compression of the cardiac
      structures, which may cause tamponade and heart failure.

PMID- 22397049
TI  - Prenatally diagnosed case of 22q11.2 deletion syndrome associated with pulmonary
      artery aneurysm.
AB  - Here, we report a new case with chromosome 22q11 deletion and cardiac anomaly
      diagnosed prenatally by echocardiography. Fluorescence in situ hybridization
      (FISH) analysis demonstrated a heterozygous deletion at 22q11.2. Echocardiography
      revealed ventricular septal defect, pulmonary atresia, and aneurysm of the main
      pulmonary artery and its branches. Pulmonary artery aneurysm (PAA) is rarely seen
      in patients with 22q11.2 deletion syndrome (22qDS). In this case, PAA was found
      by prenatal echocardiographic examination at the 25th week of gestation. To date,
      no prenatally diagnosed case of 22qDS with PAA has been reported. This is the
      first 22qDS case with PAA that was detected prenatally by FISH analysis.

PMID- 22397050
TI  - Coexistence of vitiligo and psoriasis: three case reports.
AB  - Vitiligo and psoriasis are both common diseases. However, coexistence of these
      two diseases is rare. The pathogenesis of the coexistence of vitiligo and
      psoriasis is still unknown. Herein, we report three children (11-year-old, 8-year
      old, and 7-year-old females) who attended our Department of Dermatology with
      coexisting vitiligo and psoriasis.

PMID- 22397051
TI  - Temporary atrioventricular complete block that develops following the
      transcatheter closure of ventricular septal defect.
AB  - Atrioventricular (AV) block is a potential risk after transcatheter closure of
      perimembranous ventricular septal defect (VSD) with the Amplatzer perimembranous
      device. We present herein a case of a 6.5-year-old female patient who developed
      complete AV block six days after closure of VSD and recovered with steroid and
      salicylate treatment. It is important to be alert to the development of AV block
      after transcatheter perimembranous VSD closure. Very careful monitoring of rhythm
      is mandatory during the short- and long-term follow-up.

PMID- 22397052
TI  - Metabolic cataract in an 8-year-old diabetic boy.
AB  - Cataracts are uncommon among children with insulin-dependent diabetes mellitus
      (IDDM); nonetheless, they could result in significant morbidity and a decrease in
      the life quality of these children. Duration of diabetes and metabolic control
      over the disease are important contributing factors in the development and
      advancement of cataract among diabetic pediatric patients. Ophthalmological
      examination at the time of IDDM diagnosis is recommended. Furthermore, persistent
      poor diabetic control and/or blurred vision in IDDM pediatric patients warrant
      prompt ophthalmological evaluation. We present the case of an 8-year-old with
      poorly controlled IDDM, who presented with bilateral cataract 27 months after his
      diagnosis with IDDM. We believe that such a presentation is rare; thus,
      increasing awareness of this particular diabetic complication is imperative.

PMID- 22397053
TI  - Cardiogenic shock: do not forget the possibility of Kawasaki disease.
AB  - We report the case of a six-year-old boy who presented with cardiogenic shock due
      to Kawasaki disease (KD). He was misdiagnosed at first as septic shock. After
      careful examination, he was diagnosed as KD complicated with acute coronary
      syndrome, which leads to cardiogenic shock. Cardiogenic shock is often neglected
      as a complication of KD, and it tends to be misdiagnosed. We hereby call
      attention to KD, in some cases of which, it can lead to acute coronary syndrome
      in the acute phase.

PMID- 22397054
TI  - Status dystonicus and rhabdomyolysis in a patient with subacute sclerosing
      panencephalitis.

PMID- 22397055
TI  - Transplacental transmission of influenza A (H1N1) virus--is it really possible?

PMID- 22397056
TI  - A CLASS-less Act.

PMID- 22397057
TI  - How can we bend the cost curve?

PMID- 22397058
TI  - Payment incentives and integrated care delivery: levers for health system reform
      and cost containment.
AB  - The Patient Protection and Affordable Care Act encourages use of payment methods
      and incentives to promote integrated care delivery models including patient
      centered medical homes, accountable care organizations, and primary care and
      behavioral health integration. These models rely on interdisciplinary provider
      teams to coordinate patient care; health information and other technologies to
      assure, monitor, and assess quality, and payment and financial incentives such as
      bundling, pay-for-performance, and gain-sharing to encourage value-based health
      care. In this paper, we review evidence about integrated care delivery, payment
      methods, and financial incentives to improve value in health care purchasing, and
      address how these approaches can be used to advance health system change.

PMID- 22397059
TI  - Health information technology and its effects on hospital costs, outcomes, and
      patient safety.
AB  - Underlying many reforms in the Patient Protection and Affordable Care Act (ACA)
      is the use of electronic medical records (EMRs) to help contain costs. We use
      MarketScan claims data and American Hospital Association information technology
      (IT) data to examine whether EMRs can contain costs in the ACA's reforms to
      reduce patient safety events. We find EMRs do not reduce the rate of patient
      safety events. However, once an event occurs, EMRs reduce death by 34%,
      readmissions by 39%, and spending by $4,850 (16%), a cost offset of $1.75 per $1
      spent on IT capital. Thus, EMRs contain costs by better coordinating care to
      rescue patients from medical errors once they occur.

PMID- 22397060
TI  - The impact of accelerating electronic prescribing on hospitals' productivity
      levels: can health information technology bend the curve?
AB  - This paper examines how different strategies for implementing computerized
      prescriber order entry (CPOE) impact hospitals' productivity. We used the
      American Hospital Association's Annual Survey to construct hospital-level
      measures for 1,812 facilities and analyzed the productivity indices against CPOE
      use rates. The relationship between CPOE use rates and indices for "technical
      efficiency change" and "total factor productivity" was significant. Hospitals
      introducing CPOE facilitywide in a one-year period (where usage went from zero to
      more than 50%) experienced declines in both productivity indices. One implication
      is that hospitals achieving the goals of the "meaningful use" program promoted by
      the Centers for Medicare and Medicaid Services may do so at the expense of
      productivity.

PMID- 22397061
TI  - Risk-adjusting the doughnut hole to improve efficiency and equity.
AB  - An important goal of consumer cost-sharing in health insurance is to increase
      incentives for cost containment. A relatively new cost-sharing phenomenon is the
      "doughnut hole": a gap in coverage starting at a predefined level of medical
      expenses. An important question is where to locate the starting point to achieve
      the strongest incentives for cost containment. We argue that the answer depends
      on an individual's health status. Using data from a Dutch insurer, this paper
      illustrates that using a risk-adjusted starting point results in both stronger
      incentives for cost containment and more equity than a uniform starting point.

PMID- 22397062
TI  - What can we expect from the "Cadillac tax" in 2018 and beyond?
AB  - One controversial aspect of the Patient Protection and Affordable Care Act is the
      provision to impose a 40% excise tax on insurance benefits above a certain
      threshold, commonly referred to as the "Cadillac tax." We use the Employer Health
      Benefits Survey, sponsored by the Kaiser Family Foundation and Health Research
      and Educational Trust, to examine the number and characteristics of plans that
      likely will be affected. We estimate that about 16% of plans will incur the tax
      upon implementation in 2018, while about 75% of plans will incur the tax a decade
      later due to the indexing of the tax thresholds with the Consumer Price Index. If
      the Cadillac tax is ultimately implemented as written, we find that it will
      likely reduce private health care benefits by .7% in 2018 and 3.1% in 2029, and
      will likely raise about $931 billion in revenue over the ensuing 10-year budget
      window from 2020 to 2029.

PMID- 22397063
TI  - [When well-being is threatened].

PMID- 22397064
TI  - [Altruistic kidney donation: psychological challenges].
AB  - Altruistic kidney donation challenges ethical principles, questions the
      anthropological meaning of donation and is associated with important
      psychological aspects. Obtaining free and informed consent is essential and
      requires a depth evaluation by a psychologist or a psychiatrist in order to
      identify the motivations which stimulate the desire of donation. By means of a
      psychodynamic understanding of a clinical case, we illustrate the complexity of
      the evaluation of consent and discuss the psychological issues associated with
      altruistic kidney donation.

PMID- 22397065
TI  - [Psychotropic drug prescriptions in general practice].
AB  - General practitioners treat patients with psychiatric disorders, for whom they
      have to evaluate the indication of a psychotropic medication. In addition to the
      patient's symptoms, the clinician has to take into account transferential and
      countertransferential elements linked to the prescription. Sociological factors
      also influence both the patient and the clinician, partly due to the western
      society's value of performance. Consistent with the bio-psycho-social model of
      disease, we recommend that the evaluation of the indication of a psychotropic
      medication includes the patient's symptoms, but also the psychological and
      sociological factors.

PMID- 22397066
TI  - [Mood disorders in HIV patients: a challenge for liaison psychiatry
      consultation].
AB  - Mood disorders represent the most prevalent psychiatric condition in patients
      infected by HIV virus. Screening and treatment of depression as well as the
      evaluation of the risk suicide is of the utmost importance. When
      psychopharmacological treatment is required, interaction with antiretroviral
      treatment must be carefully considered. More generally a close collaboration
      between the physician and the psychiatrist is recommended.

PMID- 22397067
TI  - [Interdisciplinary treatment of chronic low back pain: psychological aspects and
      personality traits].
AB  - Evidence on chronic low back pain treatments stresses the need for a
      multidimensional approach that aims a biopsychosocial rehabilitation. The
      caregiver team of the rheumatology division of the University Hospitals of Geneva
      has successfully applied this approach over the last years and this article
      emphasizes the value of a close collaboration with the division of liaison
      psychiatry. The use of cognitive-behavioral and psycho-educational techniques
      guaranties the definition of patient-centred and measurable treatment objectives.
      The inclusion of a psychotherapy group promotes free expression and sharing of
      psychological distress. Assessment of personality traits allows for considering
      the global nature of the patients rather than merely aiming the normalization of
      their deviant aspects.

PMID- 22397068
TI  - [Treatment of oral paresthesia in a joint stomato-psychological consultation
      model].
AB  - Medically unexplained oral paresthesia, or burning mouth syndrome, is a condition
      that primarily affects female patients, and often leads them to consult their
      dentist, who may feel helpless concerning the repeated complaints of these
      patients. Therefore, they tend to increase visits to various health professionals
      in an attempt to find a relief. Since 1996, a joint stomato-psychological
      consultation has been established in Geneva University Hospitals, in order to
      offer adequate care to these patients. This article describes this type of
      treatment, and the referral issues.

PMID- 22397069
TI  - [Effects of folic acid on cerebrovascular and cancer risks].
AB  - Homocysteine increase is associated with an elevated risk of cerebro-vascular
      (CV) disease as well as osteoporosis, dementia and depression. However, most
      secondary prevention trials did not show any CV benefit to decrease homocysteine
      levels through folate administration, with the possible exception of stroke.
      Reasons for these failures are analysed. Moreover, folate acid could decrease the
      risk of colon, breast and prostate cancers mainly in wine drinkers, whereas it
      increases the growth of preneoplasic cells of the latter cancers. In conclusion,
      folate acid does not benefit patients for secondary prevention of CV or malignant
      diseases but it still has to be proven that it could benefit patients for primary
      prevention.

PMID- 22397070
TI  - [Public health concerns by politicians, do they correspond to the concerns of
      physicians, the general population and the media?].

PMID- 22397071
TI  - [Illiteracy, a forgotten reality by prevention campaigns?].

PMID- 22397072
TI  - [Measures of radionuclear protection: optimal protection or Swiss consensus?].

PMID- 22397073
TI  - [Young people and professionals confronted with television prevention messages
      regarding extra weight gain].

PMID- 22397074
TI  - [Smokers, "neutral" cigarettes and cigarette butts].

PMID- 22397075
TI  - [Breast cancer: should we impose an organized screening?].

PMID- 22397076
TI  - [An angry surgeon, a happy biologist].

PMID- 22397077
TI  - [The large mess of clinical studies].

PMID- 22397078
TI  - Sociological knowledge and colonial power in Bombay around the First World War.
AB  - By the turn of the twentieth century a distinct 'social domain'--along with its
      constituent parts, problems and internal dynamics-was turned into a political
      entity, and a concern for state bureaucracies existed across the industrializing
      world. Specific motivations for this trend may have varied from location to
      location, but included arguments for higher industrial productivity and less
      political discontent, often intertwined with a humanitarian impulse in calls for
      better housing, expanded public health or improved working conditions. As has
      been well documented, the politicization of the social domain in early twentieth
      century Britain owes much to the consolidation of British sociology as a distinct
      discipline. Yet while the link between the rise of social politics and sociology
      has been established with regard to Britain, little has been said about the
      occurrence of this coupling elsewhere in the twentieth-century British Empire.
      This article aims to rectify that omission by showing the interplay between newly
      raised social concerns of the colonial administration in the Bombay Presidency,
      Western British India, and the establishing of sociological research within the
      borders of the Presidency around the time of the First World War. The article
      will explore how the colonial administration in Bombay planned to meet new
      demands for sociological knowledge in colonial state policy, how sociology was
      subsequently introduced into the Presidency as a research subject, and how new
      sociological methods were applied in actual colonial government.

PMID- 22397079
TI  - Making biomedicine in twentieth-century Italy: Domenico Marotta (1886-1974) and
      the Italian Higher Institute of Health.
AB  - This paper focuses on the role played by Domenico Marotta, director of the ISS
      (Higher Institute of Health) for over twenty-five years, in the development of
      twentieth-century Italian biomedicine. We will show that Marotta aimed to create
      an integrated centre for research and production able to interact with private
      industry. To accomplish this, Marotta shifted the original mission of the ISS,
      from public health to scientific research. Yet Mussolini's policy turned most of
      the ISS resources towards controls and military tasks, opposing Marotta's
      aspiration. By contrast, in the post-war years Marotta was able to turn the ISS
      into the most important Italian biomedical research institution, where research
      and production fruitfully cohabited. Nobel laureates, such as Ernst Chain, and
      future Nobel laureates, such as Daniel Bovet, were hired. The ISS built up an
      integrated research and production centre for penicillin and antibiotics. In the
      1960s, Marotta's vision was in accord with the new centre-left government.
      However, he pursued his goals by ruling the ISS autocratically and beyond any
      legal control. This eventually led to his downfall and prosecution. This also
      marked the decline of the ISS, intertwined with the weakness of the centre-left
      government, who failed to achieve structural reforms and couple the modernization
      of the country with the democratization of its scientific institutions.

PMID- 22397080
TI  - Expenditure patterns of older Americans, 2001-2009.
AB  - PRE- AND POSTRETIREMENT EXPENSES: Before retirement, people pay FICA taxes, incur
      work-related expenses, and set aside money for retirement. But after retirement,
      most people have different financial obligations, and, as a result, retirees may
      still be able to maintain their level of preretirement well-being with very
      different income levels. Studying income, expenditures, and wealth-holding
      patterns together provides a more complete idea of how people are doing in terms
      of being able to afford retirement than arbitrary estimates such as income
      replacement ratios. UNIQUE DATA: This Issue Brief examines the expenditure
      patterns of the older section of the population. It uses data from the
      Consumption and Activities Mail Survey (CAMS), a supplement to the Health and
      Retirement Study (HRS), conducted by the Institute for Social Research at the
      University of Michigan, contains detailed expenditure data on 32 categories, and
      follows the same group of individuals over eight years In addition, the income
      and wealth data available in the HRS are used to establish the financial standing
      of older households. DECLINING EXPENSES: Household expenses steadily decline with
      age. With the age 65 expenditure as a benchmark, household expenditure falls by
      19 percent by age 75, 34 percent by age 85, and 52 percent by age 95. HOME
      EXPENSES: Home and home-related expenses remain the single largest spending
      category for older Americans. On average, those over age 50 spend around 40-45
      percent of their budget on home and home-related items. RISING HEALTH CARE
      EXPENSES: Health-related expenses are the second-largest component in the budget
      of older Americans. It is the only component which steadily increases with age.
      Health care expenses capture around 10 percent of the budget for those between 50
      64, but increase to about 20 percent for those age 85 and over. DEMOGRAPHIC
      GROUPS: Singles, blacks, and high school dropouts do not have a sound financial
      standing in retirement. Their expenditures exceed their income and they hold very
      little financial wealth. The bottom income quartile, which includes mostly these
      demographic groups, has the weakest financial standing in retirement. LONG-TERM
      CARE and PRIVATE HEALTH INSURANCE: Long-term care and some form of private health
      insurance coverage have a significant effect on increased spending by older
      households.

PMID- 22397081
TI  - How does background affect attitudes to socioscientific issues in Taiwan?
AB  - Based upon the goal of scientific literacy and the importance of socioscientific
      issues (SSIs), the purpose of this study was to investigate the Taiwanese
      public's awareness of, inclinations to buy/use, and their attitudes towards three
      attributes of SSIs including genetically modified food (GM food), organic food,
      and DDT and malaria (DDT). Data from a total of 865 participants across ten
      populations (six different educational levels and four different vocations) were
      validated and analyzed. The results revealed that the awareness regarding GM food
      and DDT increased with the levels of education. The inclinations to buy/use and
      the attitudes towards the three SSIs, were not related to levels of education,
      vocation or gender, but were related to attributes of the SSIs. The implications
      for education and policy development are discussed.

PMID- 22397082
TI  - Science, the public, and social elites: how the general public, scientists, top
      politicians and managers perceive science.
AB  - This paper finds that the Croatian public's and the social elites' perceptions of
      science are a mixture of scientific and technological optimism, of the tendency
      to absolve science of social responsibility, of skepticism about the social
      effects of science, and of cognitive optimism and skepticism. However,
      perceptions differ significantly according to the different social roles and the
      wider value system of the observed groups. The survey data show some key
      similarities, as well as certain specificities in the configuration of the types
      of views of the four groups--the public, scientists, politicians and managers.
      The results suggest that the well-known typology of the four cultures reveals
      some of the ideologies of the key actors of scientific and technological policy.
      The greatest social, primarily educational and socio-spatial, differentiation of
      the perceptions of science was found in the general public.

PMID- 22397083
TI  - The cultural authority of science: public trust and acceptance of organized
      science.
AB  - Using the National Science Foundation's 2006 Science Indicators Survey, this
      study explores three distinct explanations of public attitudes. First, the
      knowledge-attitudes model refers to a well tested relationship between public
      knowledge of science and more favorable attitudes toward science. Second, the
      alienation model hypothesizes that public disassociation with science is a
      symptom of a general disenchantment with late modernity, mainly, the limitations
      associated with codified expertise, rational bureaucracy, and institutional
      authority. A third approach emphasizes the cultural meaning of science: how
      various public beliefs about "what science is" relate to acceptance or
      reservations about science. The Science Indicators Survey shows that US adults
      view science (what it is or should be) in three distinct ways: (1) in terms of
      having a systematic method, (2) in terms of social location (i.e., takes place in
      a university or a laboratory), and (3) in terms of knowledge that should accord
      with commonsense and tradition. The findings in this study indicate that the
      knowledge-attitudes, alienation, and cultural meanings models are all valuable
      for understanding the cultural authority of science. However, the strength of
      these explanations depends on the type of attitude analyzed.

PMID- 22397084
TI  - Changing news: re-adjusting science studies to online newspapers.
AB  - With the newspapers' recent move to online reporting, traditional norms and
      practices of news reporting have changed to accommodate the new realities of
      online news writing. In particular, online news is much more fluid and prone to
      change in content than the traditional hard-copy newspapers--online newspaper
      articles often change over the course of the following days or even weeks as they
      respond to criticisms and new information becoming available. This poses a
      problem for social scientists who analyse newspaper coverage of science, health
      and risk topics, because it is no longer clear who has read and written what
      version, and what impact they potentially had on the national debates on these
      topics. In this note I want to briefly flag up this problem through two recent
      examples of U.K. national science stories and discuss the potential implications
      for PUS media research.

PMID- 22397085
TI  - Making sense of global warming: Norwegians appropriating knowledge of
      anthropogenic climate change.
AB  - This paper studies how people reason about and make sense of human-made global
      warming, based on ten focus group interviews with Norwegian citizens. It shows
      that the domestication of climate science knowledge was shaped through five sense
      making devices: news media coverage of changes in nature, particularly the
      weather, the coverage of presumed experts' disagreement about global warming,
      critical attitudes towards media, observations of political inaction, and
      considerations with respect to everyday life. These sense-making devices allowed
      for ambiguous outcomes, and the paper argues four main outcomes with respect to
      the domestication processes: the acceptors, the tempered acceptors, the uncertain
      and the sceptics.

PMID- 22397086
TI  - Truth and opinion in climate change discourse: the Gore-Hansen disagreement.
AB  - In this paper, I discuss the "inconvenient truth" strategy of Al Gore. I argue
      that Gore's notion of truth upholds a conception of science and policy that
      narrows our understanding of climate change discourse. In one notable exchange,
      Gore and NASA scientist, James Hansen, disagreed about whether scientific
      statements based on Hansen's computer simulations were truth or opinion. This
      exchange is featured in An Inconvenient Truth, yet the disagreement is edited
      from the film and presented simply as an instance of Hansen speaking
      "inconvenient truth". In this article, I compare the filmic representation of
      Hansen's testimony with the congressional record. I place their exchange in a
      broader historical perspective on climate change disputation in order to discuss
      the implications of Gore's perspective on truth.

PMID- 22397087
TI  - Emergent technologies against the background of everyday life: discursive
      psychology as a technology assessment tool.
AB  - To understand prospective users' reactions to emergent technologies, it is
      crucial to examine the interactional contexts within which these reactions take
      place as people's reactions are shaped by issues that are not necessarily related
      to science or technology. These issues are often overshadowed or remain blind
      spots when descriptions or scenarios of proposed technologies are thematized as
      being the core objects of reference. We therefore recommend also studying
      prospective users' everyday-life practices in their own right, and in
      naturalistic settings. Insight into the social actions people accomplish in their
      everyday talk, such as establishing a particular identity, can help innovators
      translate prospective users' concerns into relevant technology characteristics.
      We propose discursive psychology as an analytic tool to do this and show its
      merit with a few illustrative examples.

PMID- 22397088
TI  - Where Christ did not go: men, women and Frusculicchi. Gender identity disorder
      (GID): epistemological and ethical issues relating to the psychiatric diagnosis.
AB  - Gender Identity Disorder (GID) is classified as a mental illness and included in
      the DSM-IV and ICD-1O. It will also be included in the DSM-V. The psychiatric
      diagnosis, in spite of some apparent advantages, has significant psychological
      and social adverse implications. This paper discusses some of the main
      epistemological reasons to consider gender variance as a mental disorder. It will
      also evaluate whether reasons of other kinds (pragmatic, rather than
      epistemological) may justify the inclusion of gender variance amongst mental
      illnesses.

PMID- 22397089
TI  - Ethics creep or governance creep? Challenges for Australian Human Research Ethics
      Committees (HRECS).
AB  - Australian Human Research Ethics Committees (HRECs) have to contend with ever
      increasing workloads and responsibilities which go well beyond questions of mere
      ethics. In this article, I shall examine how the roles of HRECs have changed, and
      show how this is reflected in the iterations of the National Statement on Ethical
      Conduct in Human Research 2007 (NS). In particular I suggest that the focus of
      the National Statement has shifted to concentrate on matters of research
      governance at the expense of research ethics, compounded by its linkage to the
      Australian Code for the Responsible Conduct of Research (2007) in its most recent
      iteration. I shall explore some of the challenges this poses for HRECs and
      institutions and the risks it poses to ensuring that Australian researchers
      receive clear ethical guidance and review.

PMID- 22397090
TI  - Contextualising merit and integrity within human research.
AB  - The first consideration of any Australian Human Research Ethics Committee should
      be to satisfy itself that the project before them is worth undertaking. If the
      project does not add to the body of knowledge, if it does not improve social
      welfare or individual wellbeing then the use of human participants, their tissue
      or their data must be questioned. Sometimes, however, committees are criticised
      for appearing to adopt the role of scientific review committees. The intent of
      this paper is to provide researchers with an understanding of the ethical
      importance of demonstrating the merit of their research project and to help them
      develop protocols that show ethics committees that adequate attention has been
      paid to this central tenet in dealing ethically with human research participants.
      Any person proposing human research must be prepared to show that it is
      worthwhile. This paper will clarify the relationship between research merit and
      integrity, research ethics and the responsibilities of human research ethics
      committees.

PMID- 22397092
TI  - Effect of taurine and gold nanoparticles on the morphological and molecular
      characteristics of muscle development during chicken embryogenesis.
AB  - The objective of the present investigation was to evaluate the effects of taurine
      and Au nanoparticles on the expression of genes related to embryonic muscle
      development and on the morphological characteristics of muscles. Fertilised
      chicken eggs (n = 160) were randomly divided into four groups: without injection
      (Control) and with injection of Au nanoparticles (NanoAu), taurine (Tau) or Au
      nanoparticles with taurine (NanoAu + Tau). The experimental solutions were given
      in ovo, on the third day of incubation, by injecting 0.3 ml of the experimental
      solution into the air sack. The embryos were evaluated on the 20th day of
      incubation. The methods included gene expression at the mRNA and protein levels,
      immunohistochemistry, histology and microscopy. In groups NanoAu, Tau and NanoAu
      + Tau, the muscle structure and the number of muscle cells were affected.
      Furthermore, taurine increased fibre diameter, the total number of nuclei, the
      proportion of proliferating cell nuclear antigen (PCNA)-positive cells and the
      total cell number. Also, gene expression of basic fibroblast growth factor-2 and
      PCNA was downregulated. There were no significant interactions between NanoAu and
      taurine, indicating that NanoAu did not enhance the effects of taurine. It may be
      concluded that 20 days after injection, NanoAu affected some parameters of muscle
      development, but the most profound effects were those of taurine.

PMID- 22397091
TI  - Research governance and change in research ethics practices at a major Australian
      university.
AB  - Recent revisions of the National Statement on Ethical Conduct in Human Research
      and the Australian Code for the Responsible Conduct of Research put a great
      emphasis on research governance. Institutional responsibility for the governance
      of the research is not limited only to the ethical review by the Human Research
      Ethics Committee (HREC), but also to the accountability for quality, safety,
      privacy, risk management and financial management of the research. Despite the
      development of proposed research governance frameworks, many Australian
      institutions do not have such structures in place and rely excessively on HRECs
      to perform administrative functions that are not their responsibility. In this
      paper we report on implementation of a research governance framework at
      University of New South Wales which led to reduced HREC workload and allowed more
      attention to its core functions. We present the approach undertaken by the
      university to separate the ethical review process by HREC from the research
      governance. We recommend that with proper research governance frameworks in
      place, the role of HRECs and the institutional responsibility of governance of
      the research can be defined clearly.

PMID- 22397093
TI  - Intestinal concentrations of free and encapsulated dietary medium-chain fatty
      acids and effects on gastric microbial ecology and bacterial metabolic products
      in the digestive tract of piglets.
AB  - The influence of low dietary levels of free and encapsulated medium-chain fatty
      acids on their concentrations in the digesta, the gastric microbial ecology and
      bacterial metabolic products in the gastrointestinal tract (GIT) in weaned
      piglets was studied. Starting after weaning, 36 piglets were fed a diet without
      (Control) or with medium-chain fatty acids uncoated (MCFA) or coated with
      vegetable fat and lecithin (MCFAc). After 4 weeks, the animals were killed, and
      digesta from the stomach and different sections of the GIT were collected. The
      concentrations of caprylic (p < 0.001) and capric (p = 0.001) acids were higher
      in the stomachs of piglets fed diets MCFA and MCFAc compared to the Control
      group. The concentrations dropped rapidly along the GIT, regardless of
      encapsulation, and tended to be higher in groups MCFA and MCFAc compared to the
      Control. Compared to the Control group, ingestion of diet MCFAc led to an
      increase in the number of eubacteria (p = 0.001), enterobacteriaceae (p < 0.001),
      clostridial clusters I (p = 0.001) and IV (p = 0.019), Lactobacillus johnsonii (p
      < 0.001) and Lactobacillus amylovorus (p = 0.001) in gastric contents. A similar
      trend was seen with diet MCFA. Relative concentrations of short-chain fatty acids
      were characterised by lower propionic acid levels (p = 0.045), numerically (p <
      0.1) higher acetic, lower n-butyric and i-valeric acid concentrations in the
      small intestine. Lactic acid concentrations were not significantly changed in the
      GIT, but ammonia concentrations increased (p < 0.001) in the distal small
      intestine in the MCFA and MCFAc groups. In conclusion, medium-chain fatty acids
      affected microbial ecology parameters in the gastric contents and bacterial
      metabolites in the small intestine. At low dietary levels, medium-chain fatty
      acids may be regarded as modulators of the gastric microbiota in weaned piglets.

PMID- 22397094
TI  - Effect of oat by-product antioxidants and vitamin E on the oxidative stability of
      pork from pigs fed diets supplemented with linseed oil.
AB  - The aim of the experiment was to compare the antioxidative potential of an oat by
      product with the effect of vitamin E on the oxidative stability of pork from pigs
      fed a diet enriched with linseed oil. Thirty-four crossbreed barrows were fed
      individually from 39 to 109 kg body weight (BW) on one of four diets: a control
      diet based on barley-triticale-soybean (Diet C), a diet containing an oat
      byproduct (Diet O), and the same diets supplemented with vitamin E (100 mg/kg
      diet) (Diets CE and OE, respectively). The oat by-product, comprising oat hulls
      and bran, was included at 10 and 20% in the grower and finisher diets,
      respectively. To Diets O and OE, refined rapeseed oil was added to equalise their
      energy content to Diets C and CE. Compared to Diets C and CE, the inclusion of
      the oat by-product in Diets O and OE increased the antioxidative capacity of
      water-soluble and lipid soluble compounds in these diets. Dietary treatment did
      not influence growth performance, slaughter value, longissimus dorsi (LD) muscle
      quality measured by nutrient contents, pH, drip loss or colour. Vitamin E
      supplementation increased the alpha-tocopherol concentration in serum and meat (p
      < 0.01), and decreased the formation of thiobarbituric acid reactive substances
      (TBARS) in the fresh and stored LD (p < 0.01). In addition, diets with the oat by
      product increased serum alpha-tocopherol concentration (p < 0.01) and decreased
      the TBARS levels in the fresh and stored LD (p < 0.05), without increasing muscle
      alpha-tocopherol concentration. The obtained results indicate that the phenolic
      compounds present in oat by-products have a considerable antioxidant potential
      and a beneficial effect on the pig organism and oxidative stability of meat.
      However, dietary inclusion with the oat by-product was not as efficient as
      supplementation with vitamin E.

PMID- 22397095
TI  - The effects of added sulphur amino acids, threonine and an ideal amino acid ratio
      on nitrogen metabolism in mature, overweight dogs.
AB  - The objectives of this study were to investigate the effects of added essential
      amino acids in conjunction with a dietary lysine/MJ of 0.72 on nitrogen (N)
      metabolism in dogs. Treatments were; a control diet, a diet that provided an
      ideal amino acid profile (IAA), a diet with added total sulphur amino acids
      (TSAA), and a diet with added TSAA and threonine (TT). Diets were fed to eight
      overweight, mature, female hounds using a replicated 4 x 4 Latin Square design.
      Food intake was similar across treatments, however, food N intake was higher (p <
      0.001) for TSAA than control, IAA or TT. Nitrogen absorbed was higher (p < 0.01)
      for TSAA than IAA and control. Urea N excretion was greater for control than TT
      (p < 0.05). Urine N excretion did not differ between diets. There were no
      differences in digestibility or N retention of diets. There were no differences
      in protein turnover, synthesis, or degradation. Blood metabolites were within
      normal ranges and did not differ due to dietary treatment. Based on the
      measurements made in this study, there is no benefit for added TSAA, TT or
      additional EAA in diets for mature dogs formulated to provide a 0.72 g lysine/MJ
      ME ratio.

PMID- 22397096
TI  - Silages containing buckwheat and chicory: quality, digestibility and nitrogen
      utilisation by lactating cows.
AB  - The suitability of silages containing buckwheat (Fagopyrum esculentum) and
      chicory (Cichorium intybus) for the nutrition of dairy cows was determined.
      Buckwheat and chicory were sown in mixture with ryegrass (Lolium multilorum), and
      a pure ryegrass culture served as a control forage. Swards were harvested 55 d
      after sowing and were ensiled after wilting, without additives in small round
      bales. Finally, buckwheat and chicory made up the dietary dry matter (DM)
      proportions of 0.46 and 0.34, respectively. Concentrates were restricted to 2
      kg/d. Diets were fed to 3 x 6 late-lactating cows for 15 d at ad libitum access.
      During the collection period (days 10-15) amounts of feed intake and faeces,
      urine and milk were recorded and samples were taken. Ensilability was good for
      buckwheat and ryegrass swards, but was so less for the chicory sward, which was
      rich in total ash. The buckwheat silage was rich in acid detergent fibre (445
      g/kg DM) and lignin (75.7 g/kg DM) and contained less crude protein (135 g/kg DM)
      and ether extract (15.8 g/kg DM) than the other silages. Consistent with that,
      the apparent digestibility of the organic matter and fibre were lowest when
      feeding this silage. The potassium concentrations in the chicory and ryegrass
      silages were high (61 g/ kg) and lower in buckwheat (47 g/kg). No significant
      treatment effects on intake, body weight, milk yield or milk composition as well
      as plasma beta-hydroxybutyrate and non-esterified fatty acids occurred. Being
      lowest in nitrogen (N) content, the buckwheat silage resulted in the lowest urine
      N losses and the most efficient N utilisation for milk protein synthesis, but
      this at cost of body N retention. The results show that silages containing
      buckwheat and chicory may be used as components of the forage part of dairy cows'
      diets even though they were found to have a lower feeding value than ryegrass
      silage.

PMID- 22397097
TI  - Preliminary in vitro study on the effect of xanthohumol on rumen methanogenesis.
AB  - There is a great interest in reducing the methane emission from ruminants as one
      possible cause of global warming. The aim of the presented study was to determine
      the effects of xanthohumol, one of the hop (Humulus lupulus) phytofactors, on
      methane production, microbial population and basic parameters of ruminal
      fermentation. The experiment was carried out in a batch culture system. The basic
      substrate (400 mg) consisting of meadow hay and barley meal (60:40) was
      supplemented with 0 (Control), 0.1, 0.2 or 1.0 mg of xanthohumol. The basic
      parameters of rumen fermentation and composition of microbial population were
      measured after 24 h of incubation. For the first time, the results of this in
      vitro study have demonstrated that xanthohumol is capable to reduce the methane
      production, even at the lowest dose applied (0.1 mg/400 mg). The observed
      reduction in methane production by 12-13% was not accompanied by altering the
      basic rumen fermentation parameters. However, the practical utility of this
      supplement needs further investigation under long-term in vivo conditions.

PMID- 22397098
TI  - Healthcare in the United States.

PMID- 22397099
TI  - Interview with Scott E Armstrong, FACHE, President and Chief Executive Officer,
      Group Health Cooperative. Interview by Stephen J O'Connor.

PMID- 22397100
TI  - Nurse leaders in the boardroom: a fitting choice.

PMID- 22397101
TI  - Be compliance-ready: what to consider when acquiring a physician practice.

PMID- 22397102
TI  - Coevolution of patients and hospitals: how changing epidemiology and
      technological advances create challenges and drive organizational innovation.
AB  - Over the last 20 years, hospitals have revised their organizational structures in
      response to new environmental pressures. Today, demographic and epidemiologic
      trends and recent technological advances call for new strategies to cope with
      ultra-elderly frail patients characterized by chronic conditions, high-severity
      health problems, and complex social situations. The main areas of change surround
      new ways of managing emerging clusters of patients whose needs are not
      efficiently or effectively met within traditional hospital organizations.
      Following the practitioner and academic literature, we first identify the most
      relevant clusters of new kinds of patients who represent an increasingly larger
      share of the hospital population in developed countries. Second, we propose a
      framework that synthesizes the major organizational innovations adopted by
      successful organizations around the world. We conclude by substantiating the
      trends of and the reasoning behind the prospective pattern of hospital
      organizational development.

PMID- 22397103
TI  - Setting the stage for a business case for leadership diversity in healthcare:
      history, research, and leverage.
AB  - Leveraging diversity to successfully influence business operations is a business
      imperative for many healthcare organizations as they look to leadership to help
      manage a new era of culturally competent, patient-centered care that reduces
      health and healthcare disparities. This article presents the foundation for a
      business case in leadership diversity within healthcare organizations and
      describes the need for research on managerial solutions to health and healthcare
      disparities. It provides a discussion of clinical, policy, and management
      implications that will help support a business case for improving the diversity
      of leadership in healthcare organizations as a way to reduce health and
      healthcare disparities. Historical contexts introduce aspects of the business
      case for leveraging leadership diversity based on a desire for a culturally
      competent care organization. Little research exists on the impact that the role
      of leadership plays in addressing health disparities from a healthcare management
      perspective. This article provides practitioners and researchers with a rationale
      to invest in leadership diversity. It discusses three strategies that will help
      set the stage for a business case. First, provide empirical evidence of the link
      between diversity and performance. Second, link investments in diversity to
      financial outcomes and organizational metrics of success. Third, make
      organizational leadership responsible for cultural competence as a performance
      measure. In order to address health and healthcare disparities, collaborations
      between researchers and practitioners are necessary to effectively implement
      these strategies.

PMID- 22397105
TI  - Distinguishing community benefits: tax exemption versus organizational
      legitimacy.
AB  - US policymakers continue to call into question the tax-exempt status of
      hospitals. As nonprofit tax-exempt entities, hospitals are required by the
      Internal Revenue Service (IRS) to report the type and cost of community benefits
      they provide. Institutional theory indicates that organizations derive
      organizational legitimacy from conforming to the expectations of their
      environment. Expectations from the state and federal regulators (the IRS, state
      and local taxing authorities in particular) and the community require hospitals
      to provide community benefits to achieve legitimacy. This article examines
      community benefit through an institutional theory framework, which includes
      regulative (laws and regulation), normative (certification and accreditation),
      and cultural-cognitive (relationship with the community including the provision
      of community benefits) pillars. Considering a review of the results of a 2006 IRS
      study of tax-exempt hospitals, the authors propose a model of hospital community
      benefit behaviors that distinguishes community benefits between cost-quantifiable
      activities appropriate for justifying tax exemption and unquantifiable activities
      that only contribute to hospitals' legitimacy.

PMID- 22397104
TI  - Effective US health system websites: establishing benchmarks and standards for
      effective consumer engagement.
AB  - Hospitals and health systems are playing increasingly important roles as care
      coordination hubs and consumer information sources. In particular, the
      accountable care organization (ACO) and medical home models promoted in the
      Affordable Care Act place hospitals at the center of many activities related to
      health information exchange. Therefore, it is important for these organizations
      to have effective websites, and the need for a social media presence to connect
      with consumers is growing quickly. The purpose of this study is to assess the
      websites of hospitals and health systems on four dimensions: accessibility,
      content, marketing, and technology. In addition, an overall score is calculated
      to identify the top 25 hospital and health system websites. Specific website
      elements that healthcare managers can inspect visually are described for each
      dimension in the discussion section. Generally, hospital and health system
      websites can be more effective from an end user's perspective. In particular,
      hospitals and health systems lagged on the accessibility scale that measures the
      education level required to understand the language used on a site. The scale
      also assesses the extent to which web pages are designed for ease of movement
      from page to page using embedded links. Given that healthcare consumers come from
      every demographic and stratum of society, it is important that user-friendliness
      be optimized for a broadly defined audience. Hospital and health system websites
      can also be improved on the technology scale, as many sites do not return clear
      descriptions of links to search engines such as Google and Bing that use
      webcrawlers to collect information.

PMID- 22397106
TI  - "We were all in it together": Medicine and nursing in the 8th Evacuation
      Hospital, 1942-1945.

PMID- 22397107
TI  - Was citrulline first a laxative substance? The truth about modern citrulline and
      its isolation.
AB  - Citrulline is a non-protein amino acid and is produced by the enterocytes of the
      small bowel. The isolation though ofcitrulline is generally ascribed to the
      1930s. In the present article, we demonstrated that before 1930, there was use of
      the term citrulline, signifying a resin produced by Citrullus Colocynthis. This
      citrulline is different from modem citrulline. However, neither was modem
      citrulline isolated in 1930 but somewhat earlier. Reviewing the original
      manuscripts, Koga and Ohtake (1914) did indeed isolate citrulline for the first
      time and at least half a dozen other researchers cite their work. Even though
      their work didn't lead to the determination of the structure and nature of
      citrulline, theirs was the first to isolate it. Our results have a certain
      historical and scientific significance and are discussed in extent.

PMID- 22397108
TI  - [Study of "The Suitra of the tranquilization of hemorrhoids" and other relevant
      material].
AB  - The present paper focuses primarily on a philological and historical study of the
      Arsaprasamanisutra ("The Sutra of the tranquilization of hemorrhoids"). This
      Sutra is one of the Buddhist scriptures that are characterized by the magico
      religious treatment of various diseases, especially by means of "healing spells"
      (skt. dharani or mantra), as shown by the preliminary survey in our previous
      paper "The Tradition of healing with magical spells as seen in Buddhist texts",
      Journal of the Japan Society of Medical History 55/1 (2009), 77-96. The original
      text of the Arsaprasamanisutra, most probably written in Sanskrit, is lost
      whereas its Chinese and Tibetan translations have survived. After an introductory
      summary, we provide critically edited texts of the Tibetan and Chinese
      translations accompanied by their Japanese translations with critical notes and
      annotations. In particular, the Tibetan translation presented here has been
      critically edited for the first time on the basis of collation of the five
      editions of the Tibetan Buddhist Canon. In our next paper we will analyze the
      descriptions of hemorrhoids as found in the Sutra in comparison with those
      illustrated in classical Ayurveda literature. And we will also offer further
      observations about the methods and principles for the treatment and healing of
      hemorrhoid that are attested in Buddhist scriptures.

PMID- 22397109
TI  - [Health and garden connections between Japan and New Zealand: the impact of Bella
      and Frederic Truby King's visit to Japan in 1904].
AB  - Through the case-study of the visit of a prominent New Zealand medical reformer
      and his wife to Japan in 1904, this article examines new aspects of the health
      and environmental connections between Japan and New Zealand in the early
      twentieth century. At one level, the article analyses the broader context of
      interest in Japanese plants in New Zealand and the model of Japanese health
      reforms constituted by these connections. At another, it argues that subjects
      previously considered separate--such as modem health reform, scientific
      agriculture and gardening, and Japanese and New Zealand intellectual influences-
      need to be considered together as contemporaries understood them. Doing so, it
      suggests, enables the more accurate consideration of the intellectual and
      scientific worlds of the early twentieth century and hints at the global
      dimensions of aspects of thought and state and societal reform associated with
      modernity.

PMID- 22397110
TI  - [Siebold and Ishizaka Sotetsu's contribution to the reception of acupuncture in
      nineteenth century Europe: a comparative research based on the acupuncture
      manuscripts in the Siebold collection].
AB  - This article examines Siebold and his relations with the Tokugawa shogunate
      acupuncture doctor Ishizaka Sotetsu, based on both Western and Japanese primary
      sources. It is well known that Siebold's contribution to a better understanding
      of Oriental medicine in Europe was limited to his interest in Japanese
      acupuncture, particularly Ishizaka Sotetsu's acupuncture. However, past research
      on this subject has only relied either on documents written in Dutch by Siebold's
      disciples or on Ishizaka Sotetsu's writings on acupuncture, therefore making it
      impossible to match the Dutch translations with the original Japanese
      manuscripts. This article brings new insights in Siebold's study on Ishizaka's
      acupuncture, investigating from a comparative point of view documents held by
      Leiden University, Leiden National Museum of Ethnology, Ruhr-Universittat Bochum,
      Toyo Bunko Library and the Ishizaka family's collection. The second part of the
      article analyzes also how Siebold's interest in Ishizaka Sotetsu's acupuncture
      differs from Rhyne's and Kaempfer's interest in Japanese acupuncture

PMID- 22397111
TI  - [Insanity and suicide, as described in the "Okuni-nikki (Diaries of our clan)" of
      the Hirosaki Clan Government].
AB  - The "Okuni-nikki (Diaries of our Clan)" of the Hirosaki Clan Government covers
      the years 1661-1867. Akitomo Matsuki and Yoichi Hanada picked up medical topics
      from these diaries, and edited them in two volumes of "Tsugaru-ijibunka
      shiryoshusei: Okuni-nikki" (1993, 1994). I selected cases of insanity and suicide
      from these volumes. Selected were (1) 12 cases of insanity (in its wider sense)
      (5 cases of insanity, 2 cases of depression, a case of mania, a case of
      hypochondriasis, a case of epilepsy, a case of pavor nocturnus, and a case of
      insomnia), (2) 16 cases of suicide and self injury, cased by insanity (in its
      wider sense) (11 cases of suicide, a case of suicide and injuring another person,
      a case of attempted suicide, 2 cases of lovers' attempted suicide, and a case of
      self injury; 8 cases of them were caused by insanity), (3) 3 cases of killing and
      injuring others, caused by insanity (a case of killing another person, and 2
      cases of injuring others), (4) a drunk case of injuring another person, and (5)
      13 cases of suicide and self injury, without description of insanity (9 cases of
      suicide, 2 cases of attempted suicide, a case of lovers' suicide, and a case of
      penis cutting off). There were no described cases of possession or alcoholism. In
      the Edo Era, in several provinces and clans had legal procedure to confine insane
      patients. As for the Hirosaki Clan, I could not find clues to suggest the
      existence of such legal or customary procedures.

PMID- 22397112
TI  - Making the cloud work for healthcare: Cloud computing offers incredible
      opportunities to improve healthcare, reduce costs and accelerate ability to adopt
      new IT services.

PMID- 22397114
TI  - Transferring data securely from medical devices to EMRs: cardiac clinic moves
      closer to going paperless.

PMID- 22397113
TI  - Getting started with cloud computing: offloading ancillary applications helps
      data center expand without adding cost or staff.

PMID- 22397115
TI  - How safe is the cloud? All of the pieces are in place to enable secure and
      compliant cloud-based storage environments.

PMID- 22397116
TI  - An EHR that delivers results: Arizona doctors credit EHR with helping them grow
      their practice into the largest of its specialty in the state.

PMID- 22397117
TI  - A look at unintended consequences of EHRs: the industry needs to focus on
      building EHRs that decrease medical errors and enhance patient care.

PMID- 22397118
TI  - RCM a critical component of accountability models: Revenue cycle management holds
      the key to successful financial contracting in the world of accountability
      reform.

PMID- 22397119
TI  - Time for action: ten critical areas of ICD-10 focus for healthcare executives.

PMID- 22397120
TI  - Looking toward the future 2012 part II: industry insiders weigh in on the year
      ahead in healthcare technology.

PMID- 22397121
TI  - Overcoming the challenges of enterprise system migration: for Kettering Health
      Network, selecting the right solution has made all the difference.

PMID- 22397122
TI  - Going beyond disaster recovery: don't wait for an earthquake to set up remote
      hosting options.

PMID- 22397123
TI  - ICD-10's impact on staffing: planning and partnership now brings relief in 2013.

PMID- 22397124
TI  - Problem areas in breast cancer underwriting.

PMID- 22397125
TI  - Infant mortality: an insured population perspective.
AB  - Many insurers offer life coverage to individuals during the first year of life.
      The policies tend to have small face values, but frequently contain premium
      waiver or additional purchase options. General population mortality is
      significantly higher at this age relative to older children and even middle-aged
      adults. This article presents the mortality experience of an insured cohort in
      which death occurred under 1 year of age. In summary, the insured population's
      mortality rate was significantly lower and the leading causes of death were
      different than the general population.

PMID- 22397126
TI  - Questionnaire based mortality assessment: an exploratory analysis of NHANES III.
AB  - The need for speed and efficiency in life insurance underwriting has never been
      greater. With increasing acquisition costs, the need for timeliness to complete
      the sales process, and the need for accurate mortality prediction a great deal of
      resources have been devoted to the development of non-traditional underwriting
      processes and criteria in hopes of streamlining the process. In this paper, we
      describe an exploratory analysis of mortality linked data from the US NHANES III
      study. Our goal for this analysis was to identify mortality predictors that would
      be good candidates for further investigation in insurance applicants, especially
      in the context of simplified issue products which focus on younger age
      applicants. We identified aerobic exercise, dental health, alcohol beverage type
      and quantity, and dietary components and patterns as factors that may hold
      promise as mortality predictors in persons age 17-65. Though the limitations of
      this analysis preclude the immediate use of these factors as underwriting
      criteria, it does appear that several of these hold promise, and should be tested
      in an insurance application context. Focus groups, market testing, or even
      insertion as non-actionable questions in a subset of applications may be ways to
      collect further data on them.

PMID- 22397127
TI  - Issues in breast cancer with minimal nodal involvement.
AB  - An overview of the literature pertaining to the mortality risks posed by breast
      cancers with micrometastases or isolated tumor cells found in the lymph nodes is
      presented. Also addressed is the current debate about the appropriateness of
      omitting a completion axillary node dissection when minimal disease has been
      detected via sentinel node immunohistochemistry. A companion article will present
      an analysis of survival data generated by one particular study of women with
      microscopic nodal involvement vs those with macroscopic involvement and those
      with no nodal disease.

PMID- 22397128
TI  - Lymphangioleiomyomatosis--a brief review and estimation of excess risk.
AB  - Lymphangioleiomyomatosis (LAM) is a rare pulmonary disease in women of child
      bearing age. It is multisystem disease and affects mainly the lungs. A recently
      published Korean medical article showed a sharp increase of LAM patients in Korea
      since 2004. LAM is not discussed in the standard textbook of insurance medicine.
      This article will briefly review LAM and estimate excess risk derived from
      recently published articles.

PMID- 22397129
TI  - Laryngeal amyloidosis.

PMID- 22397130
TI  - Bradycardia in a former professional athlete.
AB  - A mild bradycardia is noted in the electrocardiogram of a former professional
      hockey player applying for life insurance. The electrocardiographic differential
      diagnosis and prognostic implications are discussed.

PMID- 22397131
TI  - Right-sided endocarditis.
AB  - Right-sided endocarditis is uncommon and usually involves the tricuspid valve. It
      occurs primarily in intravenous drug uses, and patients having pacemakers,
      central lines, or congenital heart disease.

PMID- 22397132
TI  - The use of modeling for associating test values and mortality risk.

PMID- 22397133
TI  - [Reality and mysticism--the art of El Greco].

PMID- 22397134
TI  - [The ear problem of Francis II and the British Empire].

PMID- 22397135
TI  - [Misbeliefs and reality--about hospice].

PMID- 22397136
TI  - [The family tree of Franz Liszt].

PMID- 22397137
TI  - [Science in the crosshairs of enlightenment. Significance of hypothetical
      thinking].
AB  - To further the enlightenment primarily or even only by means of science was the
      hope of most representatives of the movement of the enlightenment which gave its
      name to a whole period of European cultural history. Only a few of its
      representatives, like Montesquieu and Rousseau, doubted for good reasons, whether
      and how the goals of the enlightenment can be reached at all by the means of
      science alone. In his Discours preliminaires to the Encyclopedie D'Alembert still
      wanted to limit science proper to the narrower field of those kinds of research
      which were strictly based on observations and calculations alone. In this way he
      remained committed to Descartes' ideal method of receiving authentic knowledge
      only by deduction from evident axioms or fundamental theorems. Pascal's casual
      discovery of the calculation of probabilities allowed to apply mathematics on the
      hidden laws of the apparent casualties of the human life world. Bacon's project
      of empirical science as a rational and methodological art of conducting
      experiments could replace the methodological ideal of science more geometrico.
      Lichtenberg's refined sensibility for the subjunctive linguistic forms of
      hypothetical thinking indicates a new understanding of inventing and testing
      hypotheses as the two most important methods of the experimental sciences when
      compared to the formal sciences of logic and mathematics. Whoever is studying the
      history of science of modern times in the cross wire of the enlightenment, will
      realize soon that science has always been in need of being illuminated about its
      own chances, risks and side effects. The project of enlightenment through science
      had to be complemented by the project of an enlightenment about science right
      from its beginning. Because of the implicit risks and side effects the project of
      enlightenment has to be enlightenment despite of science and because of science.
      On the one hand, as a special form of human practice the sciences are directed
      towards theoretical goals and practical purposes such that their agents cannot be
      conscious of all aspects of their practices in advance and reflect about all of
      them at the same time. On the other hand, the agents of such scientific practices
      are rarely trained, to analyze the cognitive implications of their own actions
      with the conceptual means of philosophical analysis. Furthermore, the agents of
      scientific research are hardly able to foresee the theoretical results of their
      research or even predict the chances and risks of eventual applications with the
      methods of the social sciences. Despite of the chastening experiences with the
      ambivalence of the theoretical results and practical applications of the modern
      sciences and despite of the illuminating effects of modern history and theory of
      science, contemporary scientists are not fully conscious yet of what they are
      really doing and what science really is. The contemplative ideal of scientific
      investigations for their own sake has been replaced in modern times by the
      practical ideal of scientific research in the service of humanity. The
      emancipation of the modem sciences from philosophical authorities and religious
      institutions has freed at first the sciences from alien restrictions to their
      self-chosen objects and purposes of research. However, the increasing economic
      constraints and the political dependences prevented even more so that scientists
      could realize the autonomy which the representatives of the enlightenment had
      been hoping for. KANT defined the goal of enlightenment as "man's emergence from
      his self-incurred immaturity". Quoting HORACE'S Sapere aude! he appealed to the
      courage of his comrades to use their own reason without the guidance of others in
      philosophical and especially in religious matters. Intellectual maturity as the
      proper goal of the enlightenment remained to be an undelivered promise despite of
      the emancipation of the sciences from traditional philosophical authorities and
      religious institutions. It is not only arguable whether or not enlightenment in
      this understanding is possible for most people, but also whether it is even
      desirable for all people considering the implicit ambivalence of the modern
      sciences. Kant's main philosophical works can be adequately interpreted as the
      first and unique attempt to understand the potential of the cognitive capacities
      of human beings about the chances and risks of enlightenment itself by means of a
      critical inquiry. This holds especially for the practical fruits of the
      enlightenment as, e.g., with respect to the emancipation from superstition and
      the appeal to religious tolerance, to the republican idea of the state and the
      establishment of civil and human rights, to the humanization of the law and
      execution of legal penalty as well as the unalienable rights of each individual
      human being.

PMID- 22397138
TI  - The growth hormone-prolactin relationship: a neglected issue.
AB  - During embryogenesis, the growth hormone-secreting cells (somatotrophs) and the
      prolactin-secreting cells (lactotrophs) develop from a common progenitor cell
      (somatomammotroph). Postnatally, in situations when one of these two hormones is
      oversecreted, often the second hormone is, too. The question posed is whether the
      increased secretion of growth hormone together with that of prolactin over long
      periods of time is a risk factor for malignancy.

PMID- 22397139
TI  - Growth hormone (GH), brain development and neural stem cells.
AB  - A range of observations support a role for GH in development and function of the
      brain. These include altered brain structure in GH receptor null mice, and
      impaired cognition in GH deficient rodents and in a subgroup of GH receptor
      defective patients (Laron dwarfs). GH has been shown to alter neurogenesis,
      myelin synthesis and dendritic branching, and both the GH receptor and GH itself
      are expressed widely in the brain. We have found a population of neural stem
      cells which are activated by GH infusion, and which give rise to neurons in mice.
      These stem cells are activated by voluntary exercise in a GH-dependent manner.
      Given the findings that local synthesis of GH occurs in the hippocampus in
      response to a memory task, and that GH replacement improves memory and cognition
      in rodents and humans, these new observations warrant a reappraisal of the
      clinical importance of GH replacement in GH deficient states.

PMID- 22397140
TI  - Growth hormone and treatment outcomes: expert review of current clinical
      practice.
AB  - Although there are guidelines for treatment of short stature, open questions
      regarding optimal management of growth hormone therapy still exist. Experts
      attending six international meetings agree that successful therapy results in the
      patient attaining mid-parental height, and relies on correct diagnosis and early
      intervention. Experts advocate patient followup every 3-6 months, and that growth
      and adherence should be monitored at each visit. Growth response is variable, and
      an accepted definition of good/poor response is lacking. Combined with patient
      education and regular patient follow-up, a definition of treatment response could
      lead to improved treatment outcomes. Few experts use prediction models in
      clinical practice, but all agree that pharmacogenetics might improve prediction,
      enable early therapy modulation, and promote growth. Poor growth is often due to
      low adherence. Guidance on optimal management of growth hormone therapy is
      required, with focus on early diagnosis, dosing, treatment monitoring, adherence,
      and motivation.

PMID- 22397141
TI  - Transmission of programming effects across generations.
AB  - Numerous epidemiological studies have shown that exposure to an adverse
      environment in early life is associated with a substantially increased risk of
      later disease; a phenomenon termed 'early life programming'. There is increasing
      evidence that these effects may not be limited to the first, directly exposed
      generation but may also be transmissible to subsequent generations through non
      genomic mechanisms. There are a number of mechanisms which may underpin the
      intergenerational transmission of the programmed phenotype, including persistence
      of the abnormal environment across generations, programmed effects on maternal
      physiology and the transmission of epigenetic information through the germline.
      In this review we discuss the evidence for these mechanisms in human and animal
      studies and the potential importance of this field for child health.

PMID- 22397142
TI  - Growth hormone treatment for short stature: a review of psychosocial assumptions
      and empirical evidence.
AB  - The advent of the unlimited availability of recombinant human growth hormone
      (rhGH) ushered in a new era of clinical management options and decisions for
      children with short stature, in particular, for those without GH deficiency.
      Ethical questions about treating non-GH-deficient short-statured children with
      rhGH quickly arose. After over two decades and after several additional
      indications for rhGH use in children were approved, many issues remain relevant
      today, e.g., under what circumstances should rhGH be used; is rhGH a treatment
      for psychosocial problems; and do benefits outweigh risks? Ideally, findings from
      large placebo-controlled randomized clinical trials would inform clinical
      management decisions; however, their conduct has proved infeasible thus far.
      Still, mounting research evidence has addressed many aspects of the controversies
      in this area of elective care. Clinicians are encouraged to systematically
      explore alternative, evidence-based options to rhGH treatment with parents and
      patients as a remedy for any perceived liabilities of SS, either in the present
      or future.

PMID- 22397143
TI  - Development of human insulin-producing cells for cell therapy of diabetes.
AB  - Diabetes mellitus is characterized by the loss of insulin-producing beta cells.
      While conventional treatment results in severe long-term complications, cell
      replacement therapy is a promising approach for the cure of this disease.
      However, its application is severally limited by the shortage of donor tissue.
      Hence, great research efforts concentrate on the development of an abundant cell
      source of functional beta-like cells, by pursuing three main strategies:
      Expansion of human donor beta cells in vitro, reprogramming of other cell types,
      and directed differentiation of pluripotent stem cells, both embryonic and
      patient-derived. The goal of all these approaches has been the generation of
      cells with properties that closely resemble the beta-cell phenotype, in
      particular production and storage of adequate amounts of mature insulin, and its
      regulated release in response to physiological signals. Here we review recent
      progress in all three approaches and discuss their advantages as well as
      remaining challenges.

PMID- 22397144
TI  - Meeting highlights: Lawson Wilkins Pediatric Endocrine Society, Denver, Colorado,
      USA. April 30 - May 3, 2011.

PMID- 22397145
TI  - 2011 Annual Meeting of the Endocrine Society, Boston, Massachusetts (June 4-7,
      2011).

PMID- 22397146
TI  - The 'Fuhrerschule' in Alt Rehse: A character school for the physicians of
      National Socialist Germany.
AB  - This contribution traces the international contacts and impact of the leader
      school for German doctors ('Fuhrerschule der deutschen Arzteschaft') in Alt Rehse
      1935-1943 through studies of a visitors' book and of biographies.We suggest that
      the 'Fohrerschule', an institution providing political and ideological education
      for health professionals, interested non-German physicians to a larger extent
      than earlier described. This paper also highlights a few examples of non-German
      physicians who, for various reasons, visited the 'Fuhrerschule' in Alt Rehse.

PMID- 22397147
TI  - [Chemistry at the Medical School of Paris (1853-1875)].
AB  - The Medical School of Paris was not immune from the movement of scientific
      thought which grew during the second half of the nineteenth century. Experimental
      practice had by then become the method of scientific thought. Any scientist
      worthy of the name was expected to follow the process of observation, analysis,
      experiment and synthesis: whether on the desk or in the mind,A science of
      experimentation par excellence, chemistry became an example of a scientific
      approach that medicine needed to appropriate to itself. Between 1853 and 1884,
      there was only one Professor of Chemistry at the Medical School of Paris. Charles
      Adolphe Wurtz was dean of the School from 1866 to 1875. This article aims to
      explain the impact of his teaching and his deanship on the importance of
      chemistry in medical studies.

PMID- 22397148
TI  - A deathbed scene from the Fifteenth century.
AB  - A "retable" in medieval churches was made up of a number of tables or carved
      panels which formed a screen behind the altar.The carvings usually consisted of a
      set of related religious images, such as scenes from the Passion or of the life
      of the Virgin Mary or John the Baptist. In Scotland few of these survived the
      Reformation in their original position and those that are known are usually
      fragments which have been found in the floors or walls of buildings, or in
      graveyards.

PMID- 22397149
TI  - [The "Bibliotheque diabolique" of doctor Bourneville (1882-1902)].
AB  - Published by Dr Bourneville between 1882 and 1902, the nine volumes of la
      "Bibliotheque diabolique" represent an original editorial project, at the
      crossroads of science, history and politics. By comparing continuously ancient
      and modern clinical signs, Bourneville never ceased to prove the identity of
      diabolical possession, mystic ecstasy and hysteric diseases.The study of the
      "Bibliotheque diabolique" shows once more that building such a published
      collection was one of the basements of republican propaganda in XIXth century
      France.

PMID- 22397150
TI  - How to cope with disaster loss and mourning: Galen's paper which was lost for
      centuries.
AB  - In 2005, a paper, previously considered lost, by the famous historical physician
      Galen was found. It is entitled "On the Avoidance of Sorrow" ("[Greek characters:
      see text]") and it is a philosophical treatise concerning the handling of sorrow.
      Despite mainly talking about personal experiences and loss of fortune, Galen also
      makes some recommendations. His medical writing gives us the opportunity to find,
      in a seemingly autobiographical text, health perspectives on how to cope with
      disaster and loss and confront grief and mourning. Even compared to modern
      literature, Galen's views seem remarkably up to date.

PMID- 22397151
TI  - The first official schools for nursing education in Greece: over a century of
      tradition.
AB  - The pressing need for educated nursing staff in Greece was first recognized by
      Queen Olga and Crown Princess Sofia, at the end of the nineteenth century with
      significant international aid.As a result, the School of Nursing Sisters of the
      Sanatorium "Evangelismos" was founded in 1875 and the first Greek "School of
      Certified Nurses" of the "Saint Sophia" Children's Hospital was established in
      1897. This Children's Hospital has provided Greece with excellent trained nurses
      in Pediatric as well as Neonatal and Infant Nursing ever since. Distinguished
      nurses from abroad as well as a plethora of professors and physicians have taught
      at the school which has effectively made a mark in forming a tradition until
      today. The international concept of the school, including enhancing the young
      nurses' practice with experience from abroad is one of its most interesting
      features. The first Greek nursing schools rank among the first in the world.

PMID- 22397152
TI  - [The French members of the German Medical Society of Paris (1844-1871)].

PMID- 22397153
TI  - The history of the history of chemistry.

PMID- 22397154
TI  - Exploring early modern chemistry: the first twenty-five years of the Society for
      the Study of Alchemy & Early Modern Chemistry 1935-1960.
AB  - The article uses the recently deposited archives of the Society for the History
      of Alchemy and Chemistry to explore the ideas, motives and disagreements of its
      founders and officers between 1935 and 1960. The origin of the title Ambix for
      the society's journal is also explained. An appendix identifies the initial
      membership of the society.

PMID- 22397155
TI  - Some recent developments in the historiography of alchemy.
AB  - The number of researchers and publications devoted to the history of alchemy has
      seen exponential growth and diversification in recent decades, to such an extent
      that some scholars speak of a "New Historiography of Alchemy". On the occasion of
      the seventy-fifth anniversary of the Society for the History of Alchemy and
      Chemistry, this paper outlines some highlights of the literature since 1990, with
      a view to identify current trends but also challenges for the future. Some of the
      most important changes identified are a marked awareness of the risks of
      presentism, a shift from ambitious histories to contextualised microhistories, a
      heightened recognition of the internal diversity of historical alchemy, and a
      greater emphasis on its practical dimensions and its role in the Scientific
      Revolution. Among the challenges, the paper underscores the potential risks of an
      excessive historiographical fragmentation, the need for further interdisciplinary
      training and cooperation, and the responsibilities of alchemy historians towards
      students and the general public alike.

PMID- 22397156
TI  - The fall and rise of the history of recent chemistry.
AB  - This paper defines the history of recent chemistry, and then charts the
      disappearance of the history of recent chemistry ("how we got here" history) from
      general histories of chemistry by the late 1930s. It is also shown how the
      history of recent chemistry in the early decades of the twentieth century was
      very much the history of physical chemistry. The revival of the history of recent
      chemistry is attributed to Eduard Farber and Aaron lhde. Several attempts have
      been made since the early 1980s to promote the history of recent chemistry, with
      mixed results. The current situation is assessed, and the paper concludes with a
      proposal for the entrenchment of the subject.

PMID- 22397157
TI  - The changing role of the historiography of chemistry in continental Europe since
      1800.
AB  - Throughout the nineteenth century and the first half of the twentieth century,
      many distinguished chemists attributed an important, at times crucial, role to
      the historical narrative. When the first professional histories were published
      during the nineteenth century, their role was intimately interwoven with the
      identity of chemistry, a science that in spite (or because) of its rapidly
      growing importance in the industrialisation of Europe, did not have the same
      reputation as either the exact sciences or the medical-biological disciplines.
      With the works by Berthelot, Lippmann, and Mieli, the history of chemistry
      focused on its rich and varied documentary sources. The histories of chemistry
      produced during this period set the ground for a variety of approaches that
      reflect, to a large degree, the main currents of old and recent history of
      science. Moreover, historians of chemistry, both continental and Anglo-American,
      had a prominent role in establishing the history of science as an independent
      discipline.

PMID- 22397158
TI  - Family size and expectations about housing in the later nineteenth century: three
      Yorkshire towns.
AB  - This article illustrates how cultural history can deepen the understanding of
      demographic change, presenting evidence about ways in which rising working-class
      expectations about appropriate living standards may have created additional
      pressures on the perceived costs of child-rearing. Among the key areas of family
      consumption, housing costs are selected for examination. It is shown that higher
      expectations about appropriate housing quality put pressure on family budgets,
      augmented by the rising cost of like-for-like housing. The discussion considers
      expectations about the size of the dwelling and attitudes to furnishing the home,
      and suggests that these rising expectations helped encourage family limitation.
      Existing accounts of the fertility decline which stress the role of rising
      expectations are often too generalised: this article illustrates what can be
      gained by adding detail and geographical variation.

PMID- 22397159
TI  - Disability in Herefordshire, 1851-1911.
AB  - Disability history is a comparatively new field of study, and to date little use
      has been made of the British census as a source because of its perceived
      difficulties. This article shows that it is possible to study a local, disabled
      population in the second half of the nineteenth century from this source, even
      thought the way in which individuals' disabilities are described can sometimes
      vary from one census to the next. Age distribution for each condition and was
      found to vary between those with congenital and those with acquired conditions.
      Among those with a handicap of sight, hearing or speech a higher proportion
      remained unmarried. Disabled people were likely to remain in the parental home
      until their late thirties, and when their parents died they moved in with
      siblings or became a lodger or inmate. Although few of the disabled children
      seemed to be receiving education, over 60 per cent of the adult males were found
      to be working and almost 25 per cent of the adult females. Disabled people, it
      appears, were viewed not merely as statistics, but were included as members of
      the local population, and not always dependent members.

PMID- 22397160
TI  - Infant mortality in London, 1538-1850: a methodological study.
AB  - A review of evidence on infant mortality derived from the London bills of
      mortality and parish registers indicates that there were major registration
      problems throughout the whole of the parish register period. One way of
      addressing these problems is to carry out reconstitution studies of individual
      London parishes, but there are a number of problems with reconstitution
      methodology, including the traffic in corpses between parishes both inside and
      outside of London and the negligence of clergymen in registering both baptisms
      and burials. In this paper the triangulation of sources has been employed to
      measure the adequacy of burial registration, including the comparison of data
      from bills of mortality, parish registers and probate returns, as well as the use
      of the same-name technique. This research indicates that between 20 and 40 per
      cent of burials went unregistered in London during the parish register period.

PMID- 22397161
TI  - Debates in population history. Living same-name siblings in England, 1439-1851.

PMID- 22397163
TI  - Estimating the Cornish from the 2001 England and Wales census: adjustment and re
      analyses.

PMID- 22397164
TI  - Recent developments in making family reconstitutions.

PMID- 22397165
TI  - [Christmas-time in the history of medicine].

PMID- 22397166
TI  - [Societal responsibility of the physician].

PMID- 22397167
TI  - [A gentle artist among the "wild": the life and art of Rik Wouters].

PMID- 22397168
TI  - Credibility engineering in the food industry: linking science, regulation, and
      marketing in a corporate context.
AB  - We expand upon the notion of the "credibility cycle" through a study of
      credibility engineering by the food industry. Research and development (R&D) as
      well as marketing contribute to the credibility of the food company Unilever and
      its claims. Innovation encompasses the development, marketing, and sales of
      products. These are directed towards three distinct audiences: scientific peers,
      regulators, and consumers. R&D uses scientific articles to create credit for
      itself amongst peers and regulators. These articles are used to support health
      claims on products. However, R&D, regulation, and marketing are not separate
      realms. A single strategy of credibility engineering connects health claims to a
      specific public through linking that public to a health issue and a food product.

PMID- 22397169
TI  - What does the arrest and release of Emile Borel and his colleagues in 1941 tell
      us about the German occupation of France?
AB  - The Germans occupying Paris arrested Emile Borel and three other members of the
      Academie des Sciences in October 1941 and released them about five weeks later.
      Drawing on German and French archives and other sources, we argue that these
      events illustrate the complexity of the motivations and tactics of the occupiers
      and the occupied. While Borel and his colleagues were genuine members of the
      Resistance, and those who arrested them were full participants in a brutal
      occupation, both sides respected a bargain, of no small importance to the Vichy
      regime, that allowed the university to pursue its work if its members avoided
      overt acts of opposition.

PMID- 22397170
TI  - [A writer's look upon the world of medicine].

PMID- 22397171
TI  - [Preserving the objects of the daily life of a hospital worker: by whom and
      why?].

PMID- 22397172
TI  - WHO Expert Committee on biological standardization.
AB  - This report presents the recommendations of a WHO Expert Committee commissioned
      to coordinate activities leading to the adoption of international recommendations
      for the production and control of vaccines and other biologicals and the
      establishment of international biological reference materials. The report starts
      with a discussion of general issues brought to the attention of the Committee and
      provides information on the status and development of reference materials for
      various antibodies, antigens, blood products and related substances, cytokines,
      growth factors, and endocrinological substances. The second part of the report,
      of particular relevance to manufacturers and national regulatory authorities,
      contains WHO recommendations and guidelines on human papillomavirus vaccines;
      meningococcal A conjugate vaccines; and stability evaluation of vaccines. Also
      included are a list of recommendations, guidelines and other documents for
      biological substances used in medicine, and of international standards and
      reference reagent for biological substances.

PMID- 22397173
TI  - Reflections on international medical law.
AB  - Does international medical law exist, in the first place, as an independent area
      of study? If so, is it urgently required in an era of comparative studies?
      Namely, to what extent, if at all, international studies differ from comparative
      ones? Besides, what are the particular characteristics of such international
      discipline? Namely, what are the particular features of this field that elaborate
      on our legal and scientific understanding in sketching possible definition for
      this notion of "international medical law?" In addition, how does international
      medical law correlate with health, ethics and health policies in our globalized
      world? And finally, what are the challenges that might face the international
      community, once the concept of "international medical law" is acknowledged? This
      papers aims at establishing the conceptual grounds for these questions, thus
      calling for the acknowledgment of a new field of study described as
      "international medical law".

PMID- 22397174
TI  - When consent is not enough: the construction and development of the modern
      concept of autonomy.
AB  - This paper aims to demonstrate that there is a gap in the way patient's autonomy
      is being discussed. All attention is focused on informed consent, and this
      approach is essentially wrong. Consenting is just a part of the process of
      choosing, and is not enough to allow patients to exercise their right to
      autonomy. This can only be accomplished through the complete and understandable
      disclosure of all information regarding treatment, their options and possible
      consequences.

PMID- 22397175
TI  - The role of consent in medical research: breaking or building walls? A call for
      legislative reform.
AB  - Research has been integral to the practice of medicine for almost as long as the
      discipline has existed. Until fairly recently research used to be conducted on
      human subjects without mandatory requirement for their consent. However, over
      time medical research became associated with significant cruelty resulting in an
      outcry for regulation of research actives. This resulted in significant
      legislation in place for monitoring. Today it is mandatory to obtain consent from
      subjects before embarking on medical research, and indeed treatment. Its
      significant regulatory role notwithstanding, the issue of consent at times
      becomes a hindrance to research. This paper examines the issue of consent in
      relation to medical research in the context of present legislation. It lays out
      the background to medical research with respect to purpose, scope, standard
      protocol and related issues; it then addresses the issue of consent in various
      scenarios, highlighting problems and the need for legislative reform. It is
      maintained that while regulatory measures have brought a lot of sanity to medical
      research and the medical profession, some measures are building walls inhibitory
      to research activities. Research being integral to the development and growth of
      healthcare delivery, there is need for reformation of current medical law for
      balance between patient protectionism and progress in medical research for
      effective patient care.

PMID- 22397176
TI  - Is the codification of vulnerability in international documents a sufficient
      mechanism of protection in the clinical research ethics context?
AB  - In this paper, I argue that the codification of vulnerability in international
      regulatory guidelines, such as the Declaration of Helsinki and the document
      issued by the Council for International Organizations of Medical Sciences on
      International Ethical Guidelines for Biomedical Research Involving Human
      Subjects, do not sufficiently protect research subjects. This is true in
      particular when research is designed in developed countries but conducted in poor
      (African) countries. Furthermore, I argue that the reason for the insufficiency
      of guidelines in protecting research subjects in poor settings is due to
      vagueness in those international documents. Hence, the need for a supplementary
      instrument of protection was suggested to be employed in addition to
      international regulatory documents when clinical research is designed to be
      conducted in developing countries by investigators from affluent countries.

PMID- 22397178
TI  - Internationalizing forensic assessments of criminal responsibility.
AB  - One of the important characteristics of current medicine is that it is an
      international endeavor. The fact that medicine is a global undertaking might even
      be one of its core strengths. However, the universal nature of medicine can be
      compromised when local issues become significant factors in medical practice. In
      this paper we identify criminal law as a relevant factor complicating the process
      of internationalizing a particular medical practice: the assessment of a
      defendant within the context of the question of criminal responsibility. Since
      criminal law--especially the laws relevant to assessments of criminal
      responsibility--may differ from country to country, or rather from jurisdiction
      to jurisdiction, forensic psychiatrists face the challenge of finding common
      ground and a common framework to advance these forensic psychiatric assessments.
      We describe the current situation and argue for internationalizing the discussion
      about this assessment, pointing to the example provided by assessments of
      competence.

PMID- 22397177
TI  - Psychiatric diagnoses in legal systems: an issue of validity.
AB  - When considering psychiatric evidence, justice systems from many countries are
      frequently presented with diagnostic labels from official psychiatric
      classificatory systems. A lack of validity in much of these classificatory
      systems is receiving increasing attention. Illustrative examples include post
      traumatic stress disorder, various personality disorders and dissociative
      identity disorder. The courts and review bodies from many jurisdictions place
      tremendous faith in the present categorical classifications (e.g., DSMIV and
      ICD10). This paper questions whether the reliance on these classifications
      systems is appropriate in legal proceedings.

PMID- 22397179
TI  - Termination of pregnancy under French law: from criminalization to a right in
      accordance with international developments on women's rights.
AB  - Termination of pregnancy is the premature exit of the products of conception,
      which include the placenta, bag of waters, embryo or fetus from the uterus. In
      general, the term "termination of pregnancy" refers to non-medical termination of
      pregnancy, which is requested for different reasons other than medical ones. When
      such a request is made in countries where it is lawful, women have access to
      induced termination of pregnancy under lawful and limited conditions. However, in
      countries where the practice is illegal, women tend to suffer and die of
      complications from unsafe termination of pregnancy. Nowadays, there seems to be a
      worldwide trend towards the legalization of termination of pregnancy. The impact
      of international developments on women's rights has played an increasing role in
      improving access to termination of pregnancy. This article aims at describing how
      legalization of termination of pregnancy in France has become a right which is in
      accordance with international developments on women's rights.

PMID- 22397180
TI  - The legislation of CIS countries on the issue of genetically modified products.
AB  - Genetic engineering is a fast-moving research field that produces many
      achievements, including genetically modified organisms, which are used during the
      production of food products. Recent decades have shown that scientists, policy
      makers and the general public cannot reach a consensus about the benefits and
      hazards of genetically modified food products. Opinions are so different, and
      both sides are so well-grounded, that it is not easy to reach a conclusion about
      this scientific achievement. Nevertheless, food security is one of the main
      objectives of the state, which is responsible for providing safe food products to
      its own citizens in the marketplace. This is why states are interested in
      reviewing these scientific achievements, in terms of the state's national
      interests and the security of its citizens. This article sets forth: (1) the main
      advantages and disadvantages of genetically modified products; (2) the role of
      national legislation in the control of food security; and (3) the attitude toward
      genetically modified products in the national legislatures of CIS countries.
      Taking these points into account, the authors come to the conclusion that actual
      Azerbaijan law is not responding to the changes, which have taken place in recent
      decades, in development of the world market and technological conditions in the
      production of food products. This provides the basis to conclude that, in actual
      conditions, the rights ofAzerbaijan citizens to the safety of food products are
      not well protected. At the end of this article, the authors make recommendations
      about the necessity of amendments to the legislation in their own country,
      towards the goal of greater control over such products in Azerbaijan.

PMID- 22397181
TI  - The association between mental disorder and crime during the Byzantine Empire.
AB  - From a social, administrative and political point of view, the Byzantine Empire
      was a direct continuation of the Greco-Roman world, with the Greek-Orthodox
      Church playing an important role in the formation of the Byzantium's unique
      identity. This continuity is obvious when one studies the legislation of the
      Empire. This legislation had specific provisions for insane offenders with regard
      to their legal and social handling. In this article we review these laws and
      present some interesting legal, psychiatric and social issues.

PMID- 22397182
TI  - The role of family members and close persons in health-care treatment of
      incompetent patients: a Portuguese approach.
AB  - This article analyses the role of family members and other close persons in the
      health-care decisions of incompetent patients. It will scrutinize the right to
      visit a patient in hospital and the importance of the beloved ones in that
      vulnerable stage of life. It notices a change in society recognized by law in two
      dimensions: the increasing autonomy of the patient, while nominating the persons
      who may visit at the hospital or who may participate in the decisions or even
      appointing a health care proxy; secondly the important role of close persons and
      friends. This signifies a changing family structure, whereby affections may take
      supremacy over traditional institutions. There will also be a reference to PVS
      cases and decisions concerning the collection of organs. Finally the importance
      of an advance directive that may be binding through procedural control is
      affirmed. Finally, these themes show the autonomy of medical law in several
      domains: sources of law, methodology and scope.

PMID- 22397183
TI  - The legal grounds regarding clinical trial in Turkey.
AB  - The first mention of clinical trials in a legal document occurred in Turkey many
      years before the Helsinki Declaration or Belmont report; issued in 1926, the Code
      of Pharmaceutical Products and Preparations No. 1262 law carries the statement:
      "Experimental drugs can be used in a patient only by his/her permission". Then
      the other regulation is the Regulation on Medical Deontology, dated 1960, and
      still in force. Article 10 and 11 of this Regulation address physicians and
      dentists who are conducting research. After periods of misconducted and ill
      designed studies, the modern era of clinical trials began in 1993 with the
      introduction of the "Drug Research Bylaw". This document was directly influenced
      by the initial drafts of ICH-GCP Guidelines, and some parts were very similar.
      This became the main document that regulates the conduct of clinical trials in
      Turkey. A good clinical practice (GCP) guidelines document was added in 1995. On
      the other hand, an amendment made to Article 90 of the New Turkish Penal Code No.
      5237 of 26 September 2004, which will come into force on 1st April 2005,
      envisages that in conflicts between international treaties concerning basic
      rights and freedoms and national laws, priority will be given to the
      international treaties. Therefore, in Turkish law, international treaties
      concerning basic rights and freedoms are given precedence as compared with
      national laws and other regulations. The Article stipulates the conduct of
      research on conditions such as not violating human well-being and dignity.

PMID- 22397184
TI  - Consent to medical research of vulnerable subjects from the French point of view:
      the example of consent in research in the case of Alzheimer disease.
AB  - The consent to research is the expression of autonomy. Some groups are vulnerable
      and cannot give free consent because their conditions limit their decision making
      or because they are unable to consent themselves (minor, incompetent adults).
      International standards and recommendations for medical research protect
      vulnerable subjects (article 17 of the Helsinki declaration, guidelines 9 and 13
      of the CIOMS, article 17 of the Oviedo Convention). French Law protects mostly
      three categories of vulnerable people: minors, adults with a legal
      representative, and the people living in sanitary and social establishments.
      Specific protection is given as well to pregnant women, detainees and persons
      with psychiatric disorders in involuntary commitment. From the example of
      research with Alzheimer patients the authors show the original provisions of
      French legislation to involve in medical research incompetent patients with or
      without legal protection. Clinical research on Alzheimer's disease poses
      challenges as never before to research ethics. In fact, the development of the
      disease progressively reduces the patient's ability to make choices: the latter
      is no longer capable, but is not totally incapacitated. Several solutions are
      offered for a "proxy" consent or authorisation.

PMID- 22397185
TI  - [Possible solution for current gaps in nursing care. Cutting off old braids].

PMID- 22397186
TI  - [Contra: physician assistants exacerbate the deficiency in operating room
      specialists. More questions than answers].

PMID- 22397187
TI  - [Nursing care in Ghana. Family caregivers wash bedding in the river].

PMID- 22397188
TI  - [Conscious operation: the patient perspective. Brain exposed patient during
      awareness].

PMID- 22397189
TI  - [Instructing foreign patients before medical interventions. "No more baby"!].

PMID- 22397190
TI  - [Berlin Charite: patient safety systems in intensive care. Using errors to
      prevent errors].

PMID- 22397191
TI  - [Communication in the operating room. Stress may not be an excuse for loss of
      values].

PMID- 22397192
TI  - [Implementation of section 87b of the guidelines of SGB XI--the point-of-view of
      the nurses aides].
AB  - According to section 87b of the guidelines of SGB XI (German Social Security
      Statutes), German nursing homes are authorised to recruit specially trained
      nurses aides for additional care and stimulation of high maintenance residents
      suffering from dementia or mental disabilities. This regulation started in July
      2008. The nursing aides areespeciallytrained laypeople. Despitetheguidelines,
      local practice may be different. The scientists carried out a qualitative study.
      The aim of this study was to evaluate the implementation of the guidelines from
      the nurses aides' perspective. The objective was to describe the implementation
      ofthe guidelines and to identify beneficial and restrictive elements of the
      nurses aides practice in order to improve the development of the guidelines. Four
      nurses aides in four different nursing homes were questioned with semi-structured
      interviews. Data analysis was performed using a qualitativecontentanalysis as
      developed byMayring.Thefindings show that the effective tasks and methods of the
      nurses aides fit largely into the guidelines, and the subjects look upon their
      assignment favourably. All of the subjects were continuously supervised and felt
      well integrated. Potential conflicts in cooperation with the professional
      caregivers were due to different understandings of the roles and assignment of
      tasks. The quality of nurses aides' training was rated differently. A close
      connection to the client's behaviour and the nurses aides practice proved to be
      helpful. The results may indicate that although there is concordance with the
      guidelines and with the implementation as well as job satisfaction for the nurses
      aides, for the maintenance of satisfaction and a long-term effective guideline
      implementation some aspects should be considered and improved.

PMID- 22397193
TI  - [Music therapy in terminal care. Does music therapy have a beneficial effect on
      the process of dying?].

PMID- 22397194
TI  - [Best practice: basal stimulation as nursing service. "Well, that is not possible
      for us"!].

PMID- 22397195
TI  - [The Bochum University of Public Health has has lifted a nursing degree
      curriculum out of baptism. Studying nursing care].

PMID- 22397197
TI  - [Nurnberg: nursing in the 19th century. A short prayer three times a day].

PMID- 22397196
TI  - [Nurses as witnesses in a legal process. The right to remain silent and its
      limits].

PMID- 22397198
TI  - [Backache as the main complaint. From osteoporosis to tumor].

PMID- 22397199
TI  - [Pre- and postoperative nursing care of anus praeter. Preparing and follow-up].

PMID- 22397200
TI  - Vitamin D supplementation in babies. Opinions of mothers.

PMID- 22397201
TI  - Stillbirth: the other half of perinatal mortality.

PMID- 22397202
TI  - Dietary iodine intake in pregnancy: an update.

PMID- 22397203
TI  - Medicine: who needs it?

PMID- 22397204
TI  - Impact of second reminder invitation on uptake of screening and cancer detection
      in BreastCheck.
AB  - This research aims to quantify the impact of reminder invitations on uptake and
      cancer detection in Ireland. Examination of BreastCheck's clinical database (2000
      2010) to determine number of women screened following first invitation and after
      reminder; comparison by age group and screening phase with outcomes of recall
      rate, cancer detection and true positive rates. Of 819,182 first invitations sent
      448,974 (54.8%) women attended. 245,157 (66.2%) women attended after reminder
      invitations, increasing uptake by 29.9% to 694,131 (84.7%) and cancers detected
      by 1,550 (35%). Women awaiting a reminder were less likely recalled for
      assessment 9,555 (3.9%) than respondents to first invitation 2,887 (4.04%)
      (p=0.004). Younger, mainly initial women were more likely recalled for assessment
      after first invitation. There was no difference between cohorts for cancer
      detection rate or true positive rate. Reminders increased uptake, supporting
      international evidence. For programme efficiency attendance at first invitation
      is optimal. For maximum programme effectiveness attendance must be encouraged
      with reminders.

PMID- 22397205
TI  - Childhood obesity: parents fail to recognise, general practitioners fail to act.
AB  - General Practitioners (GPs) have an important role to play in recognition of and
      intervention against childhood obesity in Ireland. Data were collected
      prospectively on a cohort of children aged 4-14 and their parents (n = 101 pairs)
      who attended consecutively to a semi-rural group general practice. Parents
      estimated their child's weight status. Actual weight status was determined for
      both parent and child using the United States Centres' for Disease Control's BMI
      for-age references. 15 (14.9%) of the children and 49 (51.6%) of the parents were
      overweight or obese. While 71 (95.5%) of normal weight status children were
      correctly identified, parents showed poor concordance in identifying their
      children as overweight 2 (18.2%) or obese 0 (0%). BMI was only evidently recorded
      in the clinical records of 1 out of 15 cases of overweight children identified.
      With parents failing to recognise childhood obesity, GPs have a responsibility in
      tackling this problem at a family level.

PMID- 22397206
TI  - Review of acute cancer beds.
AB  - A review of admissions to cancer services at University Hospital Galway (UHG) was
      undertaken to assess the appropriateness of hospital usage. All cancer specialty
      patients admitted from 26-28 May 2009 were reviewed (n = 82). Chi square tests,
      Exact tests, and One-way ANOVA were utilised to analyse key issues emerging from
      the data. Fifty (61%) were classified as emergencies. Twenty three (67%) occupied
      a designated cancer bed with 24 (30%) in outlying non-oncology wards. The mean
      length of stay was 29.3 days. Possible alternatives to admission were identified
      for 15 (19%) patients. There was no evidence of discharge planning for 50 (60%)
      admissions. There is considerable potential to make more appropriate utilisation
      of UHG for cancer patients, particularly in terms of reducing bed days and length
      of stay and the proportion of emergency cancer admissions, and further developing
      integrated systems of discharge planning.

PMID- 22397207
TI  - Diagnosing the doctors' departure: survey on sources of dissatisfaction among
      Irish junior doctors.
AB  - There has been a significant decline in the number of applications for non
      consultant hospital doctor (NCHD) posts in Ireland over the last 18 months. We
      conducted an online, anonymous survey of Irish NCHDs to establish levels of
      satisfaction, sources of dissatisfaction and the major reasons for junior doctors
      seeking work abroad. 522 NCHDs took the survey, including 64 (12.3%) currently
      working outside of the Republic. 219 (45.8%) were slightly dissatisfied and 142
      (29.7%) were extremely dissatisfied with practising medicine in Ireland. Major
      sources of dissatisfaction included the state of the health care system, staffing
      cover for leave and illness, the dearth of consultant posts and the need to move
      around Ireland. The most important reason for NCHDs wishing to leave was to seek
      better training and career opportunities abroad.

PMID- 22397208
TI  - The incidence of injury presentations to emergency departments: what we don't
      know can hurt us.
AB  - The incidence of injury presentations to emergency departments in the Republic of
      Ireland has not been established. Data were collected relating to all injuries
      that presented on every eighth day in July-December 2005 to the three hospitals
      in Cork City. In total, 2,967 injury presentations were recorded. The total, male
      and female age-adjusted rate of injury presentations was 11,322, 13,933 and 8,550
      per 100,000, respectively. The peak male rate was among 15-29 year-olds (26,735
      per 100,000), 2.5 times the female rate in the same age range (10,719 per
      100,000). The peak female rate was among over 85 year-olds (18,543 per 100,000).
      Place of injury, activity at time of injury and underlying substance/object
      causing injury were unspecified for 44%, 46% and 43% of recorded injuries.
      Improving the recording of injury data needs to be prioritised in Irish emergency
      departments ideally in conjunction with the development of a national injury
      surveillance system.

PMID- 22397209
TI  - A critical evaluation of HIPE data.
AB  - Resource allocation and planning of future services is dependent on current
      volumes, making it imperative that procedural data is accurately recorded. We
      sought to evaluate the effectiveness of the information gathered by the Hospital
      Inpatient Enquiry (HIPE) system in recording such activity. Five index vascular
      procedures (open/endovascular abdominal aneurysm repair, carotid endarterectomy,
      lower limb angioplasty/bypass) were chosen to reflect activity. The Economic and
      Social Research Institute (ESRI), and HIPE databases were interrogated to obtain
      the regional and hospital specific figures for the years 2005, 2006 and 2009, and
      then compared with the prospective vascular database in St James's hospital. Data
      for 2006 (the most recent year available) shows significant discrepancies between
      the HIPE and vascular database figures for St James's hospital. The HIPE and
      database figures respectively for; open aneurysm 13/30 (-50%), endovascular
      aneurysm 39/31 (+25%), carotid 62/48 (+29%), angioplasty 242/111 (+100%) and
      bypass 24/10 (+100%) These inaccuracies are likely to be magnified on a regional
      and national level when pooling data.

PMID- 22397210
TI  - Fracture liaison service in a non-regional orthopaedic clinic--a cost-effective
      service.
AB  - Fracture liaison services (FLS) aim to provide cost-effective targeting of
      secondary fracture prevention. It is proposed that a dedicated FLS be available
      in any hospital to which a patient presents with a fracture. An existing
      orthopaedic clinic nurse was retrained to deliver a FLS. Proformas were used so
      that different nurses could assume the fracture liaison nurse (FLN) role, as
      required. Screening consisted of fracture risk estimation, phlebotomy and DXA
      scanning. 124 (11%) of all patients attending the orthopaedic fracture clinic
      were reviewed in the FLS. Upper limb fractures accounted for the majority of
      fragility fractures screened n=69 (55.6%). Two-thirds of patients (n=69) had
      reduced bone mineral density (BMD). An evidence based approach to both non
      pharmacological and pharmacotherapy was used and most patients (76.6%) receiving
      pharmacotherapy received an oral bisphosphonate (n=46). The FLS has proven to be
      an effective way of delivering secondary prevention for osteoporotic fracture in
      a non-regional fracture clinic, without increasing staff costs.

PMID- 22397211
TI  - Obstetric outcome with low molecular weight heparin therapy during pregnancy.
AB  - This was a prospective study of women attending a combined haematology/obstetric
      antenatal clinic in the National Maternity Hospital (2002-2008). Obstetric
      outcome in mothers treated with low molecular weight heparin (LMWH) was compared
      to the general obstetric population of 2006. There were 133 pregnancies in 105
      women. 85 (63.9%) received prophylactic LMWH and 38 (28.6%) received therapeutic
      LMWH in pregnancy. 10 (7.5%) received postpartum prophylaxis only. The perinatal
      mortality rate was 7.6/1000 births. 14 (11.3%) women delivered preterm which is
      significantly higher than the hospital population rate (5.7%, p<0.05). Despite
      significantly higher labour induction rates (50% vs 29.2% p<0.01), there was no
      difference in CS rates compared to the general hospital population (15.4% vs
      18.9%, NS). If carefully managed, these high-risk women can achieve similar
      vaginal delivery rates as the general obstetric population.

PMID- 22397212
TI  - Mental illness and structural violence.

PMID- 22397213
TI  - The presentation of coeliac disease as a disease-related malignancy.

PMID- 22397214
TI  - Prognosis tool based on a modified children's implant profile for use in
      pediatric cochlear implant candidacy evaluation.
AB  - OBJECTIVES: We developed a prediction tool to assist in evaluation of pediatric
      candidates for cochlear implantation (CI) and to help plan for preoperative and
      postoperative support. METHODS: Between 1995 and 2005, 277 patients underwent CI
      at Children's Hospital Boston. Of these 277 patients, 250 had at least 2 years of
      post-CI follow-up and adequate pre-CI information for rating by our prediction
      tool. Of the 250, 106 were randomly selected for inclusion. The patients were
      divided into group A (auditory/oral communicator); group B (auditory/oral
      communicator with visual assistance), group C (visual/manual communicator with
      auditory/oral skills assistance), and group D (will not derive communicative
      benefit from implant). Predictions were performed with clinical assessment and
      two statistical techniques: regression modeling and classification and regression
      tree (CART) analysis. RESULTS: Among patients who became auditory/oral
      communicators (group A), clinical assessment predicted that outcome accurately
      65% of the time, CART analysis had intermediate sensitivity (79%), and regression
      modeling was the most sensitive (95%). Groups B through D were predicted 45% of
      the time by regression modeling, 90% of the time by clinical assessment, and 100%
      of the time by CART analysis. CONCLUSIONS: A combination of speech-language,
      medical, and educational constructs can provide a reliable prediction of the
      communication outcome. Our goal for the prognosis tool is to make it part of the
      overall candidacy process in supporting decision-making about CI and planning for
      post-CI therapy.

PMID- 22397215
TI  - Audiometric characteristics in patients with noise-induced hearing loss after
      sodium enoxaparin treatment.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of sodium enoxaparin
      treatment on patients with noise-induced hearing loss. METHODS: Sixty patients
      with noise-induced hearing loss were included and randomly divided into two
      numerically equal groups. Group A underwent therapy with sodium enoxaparin for 10
      days, followed by an additional 10 days of treatment after 10 days of no
      treatment. Group B received placebo as a control. Before treatment, at the end of
      treatment, and 2 months after the end of treatment, all patients underwent
      evaluation by laboratory tests, pure tone audiometry, transient evoked
      otoacoustic emissions (TEOAEs) testing, distortion product otoacoustic emissions
      (DPOAEs) testing, and auditory brain stem response testing. RESULTS: In contrast
      to group B, at the end of the treatment in group A pure tone audiometry showed a
      significant (p < 0.05) improvement of the audiometric thresholds at 0.5, 1, 2, 4,
      and 8 kHz. Depending on the air and bone conduction thresholds, TEOAEs and
      DPOAEs, which had previously been absent, were evoked at the frequencies
      examined. These improvements were confirmed at last follow-up. We found no
      significant differences in auditory brain stem responses or laboratory results.
      CONCLUSIONS: These preliminary data encourage further studies to collect
      additional evidence on the effect of sodium enoxaparin in preventing the
      development of noise-induced hearing loss.

PMID- 22397216
TI  - Nasal floor free mucosal graft for skull base reconstruction and cerebrospinal
      fluid leak repair.
AB  - OBJECTIVES: Donor sites for free mucosal grafts for endoscopic endonasal
      reconstruction of the skull base have traditionally included the middle
      turbinate, the inferior turbinate, and the nasal septum. The aim of this study
      was to demonstrate a free mucoperiosteal graft from the nasal cavity floor as a
      simple alternative donor site for mucosal grafts. METHODS: In a cadaver study
      with clinical correlation, we performed endoscopic endonasal harvest of the nasal
      floor free mucosal graft on two sides of a cadaveric nasal cavity. We also
      describe the cases of two patients in whom a nasal floor free mucosal graft was
      used to repair a skull base defect. RESULTS: The harvest of a nasal floor free
      mucosal graft is a quick, potentially less morbid method of obtaining free
      mucosal grafts. In the cases examined, use of this graft carried minimal
      morbidity and allowed for successful reconstruction of a skull base defect.
      CONCLUSIONS: Harvest of nasal floor mucosa is a technically simple method of
      obtaining free mucoperiosteum for reconstruction of the skull base.

PMID- 22397217
TI  - Pseudo-sudden deafness.
AB  - OBJECTIVES: We describe the symptom complex and management of a clinical entity
      we refer to as "pseudo-sudden deafness," which is an episode of acute otitis
      media that leads to sensorineural hearing loss with reduced speech
      discrimination. METHODS: We included 8 adult patients with audiometrically
      confirmed, asymmetric sensorineural hearing loss with decreased speech
      discrimination that presented after an episode of acute otitis media. Magnetic
      resonance imaging ruled out retrocochlear disease. Both physical examination and
      myringotomy helped confirm the diagnosis of serous otitis media (SOM).
      Myringotomy, tympanostomy tubes, oral antibiotics, and otic antibiotic-steroid
      drops were used to treat the SOM. Oral steroids were used to treat the
      sensorineural component. RESULTS: Pretreatment and posttreatment audiograms
      showed an improvement in speech discrimination score, pure tone thresholds, or
      both after treatment for underlying SOM and sensorineural hearing loss in 6 of
      the 8 patients. CONCLUSIONS: Patients who present with an acute onset of
      unilateral sensorineural hearing loss with decreased speech discrimination may be
      mistakenly thought to have idiopathic sudden sensorineural hearing loss when, in
      fact, they may have an SOM-induced phenomenon that is potentially reversible. The
      distinguishing feature is a preexisting otitis media, which must be treated
      first, before the administration of steroids.

PMID- 22397218
TI  - Parotidectomy: a 17-year institutional experience at a rural academic medical
      center.
AB  - OBJECTIVES: We describe the parotidectomy experience at a single rural
      institution over 17 years. METHODS: We retrieved the records of all patients who
      underwent parotidectomy for any nontrauma indication (current procedural
      terminology codes 42410, 42415, 42420, 42425, and 42426) from January 1990 to
      June 2007 at Dartmouth-Hitchcock Medical Center, a rural medical center that
      provides both primary and tertiary care to a local population of 14,000, with a
      catchment area of 600,000 people. Information was collected on initial patient
      presentation, use of fine-needle aspiration, extent of surgery, final pathologic
      diagnosis, and complications. RESULTS: We performed 341 parotidectomy procedures
      in 334 patients. The largest number of malignancies came from metastatic tumors;
      squamous cell carcinoma was the most common (37% of malignancies). The most
      common presenting complaint overall was a painless mass. The most common
      complication was facial weakness in 17% (57 of 341); 36 of the 57 cases of facial
      weakness (63%) were associated with surgery for malignancy. The most common
      benign tumor was pleomorphic adenoma (114 of 186; 61%). Mucoepidermoid carcinoma
      was the most common primary parotid malignancy (12%). CONCLUSIONS: In this 17
      year rural case series of all parotidectomy procedures done for nontrauma
      indications, the largest number of malignancies came from metastatic tumors.
      Although facial nerve paralysis is not a common complication, it occurs most
      often when surgery is performed for either primary or metastatic malignancy.
      Surgeons will benefit from this information as they counsel patients who are
      considering parotidectomy.

PMID- 22397220
TI  - Effects of early commercial air travel on graft healing rates after
      tympanoplasty.
AB  - OBJECTIVES: We sought to determine whether commercial air travel soon after
      tympanoplasty significantly affects graft healing rates. METHODS: We performed a
      retrospective analysis of 169 patients who underwent tympanoplasty from 1993 to
      2009, comparing two groups of patients: 69 patients who flew 1 day after surgery
      and 100 who did not. The confounding factors analyzed were side of surgery, size
      of perforation, surgical approach, graft material, and grafting technique. The
      primary outcome measure analyzed was successful closure of the perforation at the
      first follow-up visit, at 4 weeks, evidenced by direct otoendoscopic examination.
      RESULTS: There was no significant difference in the confounding variables between
      the two groups. There was no significant difference in the primary outcome
      measure of graft healing rates between the two groups (p = 0.494). Additionally,
      the overall graft healing rates compared favorably with previously published data
      from other authors. CONCLUSIONS: Early commercial air travel after tympanoplasty
      does not significantly affect graft healing rates and should be considered a
      relatively safe option.

PMID- 22397219
TI  - Endoscopic treatment of benign and malignant strictures of the cervical esophagus
      and hypopharynx.
AB  - OBJECTIVES: We evaluated the efficacy of endoscopic techniques employed in the
      management of cervical esophageal and hypopharyngeal strictures. METHODS: A
      series of 45 patients with cervical esophageal (35) and/or hypopharyngeal
      strictures (10) were included. Twenty-five patients (55.6%) with neoplastic
      strictures were treated for palliation alone. The stenosis was related to
      radiotherapy in 11 patients (24.4%) and to postsurgical complications in 9 (20%).
      A group of 23 patients was treated with dilation alone (group 1). A second group
      included 22 patients treated with insertion of a self-expandable stent after
      failure of dilation treatment (group 2). The swallowing test data, clinical
      notes, and surgical reports were reviewed. RESULTS: All of the patients showed
      some degree of relief of dysphagia. In group 1, 19 of the 23 patients required
      multiple dilation treatments to maintain normal deglutition. In group 2, 7 of the
      22 patients recovered regular oral feeding after stent placement, 10 patients
      reported pain and foreign body sensation, 2 patients reported pain so severe that
      stent removal was required, and 3 patients experienced stent migration. All but 3
      of the 25 patients with inoperable tumors died during follow-up, but no patients
      with benign stenosis died. CONCLUSIONS: The two groups showed comparable
      functional results. Dilation often requires multiple procedures, but is usually
      well tolerated. Placement of self-expandable stents is effective, but is
      generally less well tolerated.

PMID- 22397221
TI  - Patients with phantogeusia show increased expression of T2R taste receptor genes
      in their tongues.
AB  - OBJECTIVES: The taste receptor gene family T2R has been implicated in the
      sensation of bitter taste. Phantogeusia is a spontaneous abnormal taste with no
      external stimulus. We analyzed the expression of T2R taste receptor genes in the
      tongues of patients with phantogeusia to assess their role in the pathogenesis of
      phantogeusia. METHODS: We obtained specimens from 43 patients with phantogeusia
      and 24 normal volunteers by scraping the foliate papillae and examined these
      specimens for the expression of 10 T2R taste receptor genes using reverse
      transcription-polymerase chain reaction and electrophoresis. RESULTS: The
      expression rate (subjects with detectable expression) of the 10 taste receptor
      genes in the healthy subjects ranged from 16.7% to 100%; 3 receptor genes were
      found in 50% or fewer of these subjects. In the patients with phantogeusia, the
      expression rate was increased significantly compared to that in the healthy
      control subjects for 3 of the 10 receptor genes examined. CONCLUSIONS: Our
      results show that the expression rate of some of the T2R taste receptor genes was
      increased significantly in patients with phantogeusia. These results suggest that
      increased expression of taste receptor genes is involved in the pathogenesis of
      phantogeusia; this finding may contribute to elucidation of the mechanism of this
      disorder.

PMID- 22397222
TI  - Oval window transport of Gd-dOTA from rat middle ear to vestibulum and scala
      vestibuli visualized by in vivo magnetic resonance imaging.
AB  - OBJECTIVES: We tested our hypothesis that the oval window (OW) potentially
      functions as a route to carry substances from the middle ear to the vestibulum
      and then the scala vestibuli through the annular ligament across the
      stapediovestibular joint. METHODS: Gd-DOTA was either injected into the lateral
      attic compartment of rats with a high-performance polyimide tube in a selective
      OW delivery group, or administered to the middle ear cavity of two groups of rats
      in which the OW was either sealed or not sealed. The dynamic uptake of Gd-DOTA in
      the inner ear was visualized with a 4.7-T magnetic resonance imaging machine.
      RESULTS: In the selective OW delivery group, Gd-DOTA appeared in the vestibulum
      and in the basal turn of the scala vestibuli but not in the scala tympani on T1
      weighted images acquired at 10 minutes after Gd-DOTA administration (the earliest
      available time point of magnetic resonance imaging). In the sealed-OW group,
      immediate uptake of Gd-DOTA was absent in the vestibulum and scala vestibuli.
      Measurement of the signal ratio of the vestibulum to that of the scala tympani
      showed that selective OW delivery induced the greatest signal ratio and that
      sealing of the OW induced the lowest signal ratio. CONCLUSIONS: The OW is a
      genuine and efficient pathway to transport Gd-DOTA from the middle ear to the
      vestibulum.

PMID- 22397223
TI  - Decellularized rabbit cricoarytenoid dorsalis muscle for laryngeal regeneration.
AB  - OBJECTIVES: Although considerable progress has been made in regenerative
      medicine, a quantum step would be the replacement and/or regeneration of
      functional muscle tissue. For example, although patients' airways can now be
      successfully replaced with stem cell-based techniques, a much greater patient
      need would be addressed by regeneration of the muscles required for engineering a
      functional larynx, in which active movement is critical. The rabbit
      cricoarytenoid dorsalis muscle was chosen for the present study because it is
      equivalent to the posterior cricoarytenoid muscle, the only significant abductor
      muscle in human larynges. METHODS: Rabbit cricoarytenoid dorsalis muscles were
      harvested, and different decellularization methods were compared by use of a
      combination of histologic, immunohistochemical, and molecular techniques.
      Decellularized scaffolds were implanted into Sprague-Dawley rats as part of a 2
      week biocompatibility study to assess immunogenicity. RESULTS: Decellularization
      with a combination of latrunculin B, potassium iodide, potassium chloride, and
      deoxyribonuclease resulted in total DNA clearance and reduced levels of major
      histocompatibility complex class II expression, with relative preservation of the
      scaffold's structural integrity (collagen, elastin, and glycosaminoglycan
      content). The scaffolds showed minimal signs of rejection at 2 weeks in a cross
      species (xenotransplantation) study. CONCLUSIONS: Decellularized laryngeal
      muscles, which are nonimmunogenic, may provide the optimal scaffold source for
      the generation of a fully functional tissue-engineered larynx.

PMID- 22397224
TI  - Garlic-supplemented diet attenuates gentamicin-induced ototoxicity: an
      experimental study.
AB  - OBJECTIVES: Gentamicin sulfate is a potent aminoglycoside antibiotic associated
      with serious side effects, including ototoxicity. Garlic, with its intrinsic
      antioxidant activity, may prove beneficial in prevention of ototoxicity. In this
      study, we investigated the effect of a 4% garlic-supplemented diet on the
      ototoxicity induced by gentamicin in rats by using brain stem evoked response
      audiometry. METHODS: Eighteen male Wistar rats with an intact Preyer's reflex and
      an initial weight of 220 to 260 g were randomly assigned to a group with
      gentamicin injection and garlic supplementation, a group with gentamicin
      injection without garlic supplementation, or a control group (6 rats each group).
      Gentamicin was given by intraperitoneal injection at 120 mg/kg body weight once
      daily for 16 days. The garlic-supplemented diet was prepared by adding pulverized
      whole garlic cloves to standard chow in a 4% proportion. After 21 days, hearing
      thresholds were evaluated by use of brain stem evoked response audiometry at 10
      kHz. RESULTS: The mean (+/- SD) amplitudes of the auditory thresholds (sensation
      level) measured by use of brain stem evoked response audiometry for the group
      with garlic supplementation, the group without garlic, and the control group were
      43.3 +/- 8.16, 78.0 +/- 4.47, and 16.7 +/- 5.16 dB sensation level, respectively.
      The differences were statistically significant (p < 0.05). CONCLUSIONS: A garlic
      supplemented diet seems to attenuate aminoglycoside-induced hearing loss.

PMID- 22397225
TI  - Bariatric surgery for severe obesity.

PMID- 22397226
TI  - Talking culture, crying health, hoping for nothing: surviving the many flyers
      above the human rights global cuckoo's nests.
AB  - Today's talk about any health issue is part of a wider web of neoliberal
      destructive processes of which all fall into the category of discriminating
      populations and their cultures, downgrading their right to life and violating
      their human dignity. Poor health, poverty stricken health systems and screaming
      epidemiological factors make just one more triangle of the successive visible
      consequences of destruction that equals to the violation of human dignity, to
      begin with. Yet no correction is possible since every problem is tied to the
      double standard perceivement of Human Rights. The author is engaged in presenting
      a need of a deeper auto-reflexive work-through of our human approachments and
      biological realities. This urgent stance is based on the new, set by Kalny (2009)
      and Baxi (2006), orientation towards a critical reading of the Human Rights and
      the advocacy toward differentiating between the politics for human rights and
      politics of human rights (the later being the politics of rights
      instrumentalization). Health and its un-sustainability is one of the most
      dramatic areas in which this differentiation of ones approaches is dramatically
      felt and needed. The end conclusions are envisioned to support the already
      existing field of a number of dedicated critical medical anthropologists, as well
      as authors across all fields, in their demand for, nothing more or less than, the
      dignity for the populations that they/we daily represent.

PMID- 22397227
TI  - Psychiatric hospital--from asylums to centres for mind-body wellness.
AB  - Throughout history mental illness was mystified, feared and condemned, but over
      time perception and treatment of psychiatric patients changed. Systematic care
      for the mentally ill in specialised institutions began about six hundred years
      ago. However, it was of a repressive and restrictive character towards the
      patients until as late as 19th century, a time of significant progress and
      development for the science of psychiatry. It was then that the effect of one's
      immediate environment on human emotions, mood, and recovery became the subject of
      many scientific studies, and the role of architectural design in the care and
      treatment of psychiatric patients gained much attention. Over the years
      significant evidence has been accumulated of the effect of architectural design
      on humans. However, psychiatric hospitals very often occupy buildings not
      originally designed for that specific purpose. This is the case with the Rab
      Psychiatric Hospital, demonstrating a functional and efficient use of its
      premises, which have yet to be recognised as a historical, cultural and
      architectural landmark.

PMID- 22397228
TI  - Improvement of health care for the poor in Split (southern Croatia) during the
      first half of the 19th century.
AB  - The aim of this study was to investigate the health care available for the poor
      citizens of Split during the first half of the 19th century. Soon after being
      constructed in 1797, the Civic Hospital in Split founded by the Ergovac brothers
      for the needs of the poor was transformed into a military hospital. Consequently,
      caring for this social stratum was taken over by two inadequate shelters and
      later by a small civic hospital situated in the Split suburb of Dobri. The year
      of the application of Petar Ergovac to the supreme ruler for the transformation
      of the hospital building established by his family from a military to a civil
      institution was found, as well as the correct data regarding its return to
      initial idea in 1821. On the basis of the archival documents kept in the
      Archaeological Museum in Split and in the State Archives in Zadar, the work
      organization of the Civic Hospital in Split and the first stage of its change
      from a charitable to a public health hospital institution were presented. This
      study revealed the aspiration of the authorities in the first half of the 19th
      century to improve the health system of the city of Split.

PMID- 22397229
TI  - Psychological symptoms among workers employed in companies undergoing
      privatization in postwar Bosnia and Herzegovina.
AB  - In Central and Eastern European countries, after abandoning communism,
      significant political, economic and social changes occurred, followed by the
      increase in income inequality and social disparity. The goal of this study was to
      examine the relationship between psychological symptoms and monthly income of
      employees in companies undergoing privatization. The study included 258 workers
      from seven companies undergoing privatization in the Tuzla Canton region. For the
      study purposes, the Brief Symptom Inventory (BSI) and a general questionnaire
      with questions about socio-demographic characteristics, income, and workplace,
      were used. Monthly income of the majority of workers (207 or 80.2%) was below the
      monthly income in Bosnia and Herzegovina. Workers with salaries below the average
      salary for Bosnia and Herzegovina have pronounced somatization, anxiety,
      paranoia, interpersonal sensitivity and hostility. The BSI scale yielded
      significant negative correlation between the level of monthly salary and the
      expression of psychological symptoms (r = -0.184, p = 0.002) and between the
      level of family income and the expression of psychological symptoms (r = -0.123,
      p = 0.024). Based on the study results, it was determined that socio-economic
      factors such as the level of salary and total family income and job insecurity,
      educational level, marital status and gender may be predictors of psychological
      symptoms.

PMID- 22397230
TI  - Does urban poverty increase body fluctuating asymmetry?
AB  - Perturbations during development leave enduring signs on the adult body.
      Fluctuating asymmetry (FA) is a good bio-indicator of stress during ontogeny. The
      aim of this study is to determine the effect of urban poverty on the fluctuating
      asymmetry of young Turkish males. Young males from a lower socioeconomic group (N
      = 140, Mean age = 18.17 +/- 0.61) were selected from slum areas of Ankara, the
      capital of Turkey, where urban poverty is intense. An upper socioeconomic group,
      on the other hand, consisted of students from two private colleges and included
      children from some of the richest families in Turkey (N = 120, Mean age = 18.08
      +/- 0.54). Eight anthropometric traits of all subjects were measured. Considering
      the seven measurements demonstrate ideal FA, the individuals living in poor areas
      of the city displayed higher FA. The discrepancy between the two groups was even
      greater for a measure of composite FA. In conclusion, poor living conditions in
      Ankara, where urban poverty is intense, adversely impact the developmental
      stability of young Turkish males.

PMID- 22397231
TI  - Do kinesiologic activities change aberrant behavior in preschool children?
AB  - An experimental treatment was carried out in a sample of 117 preschool children
      by applying kinesiologic activities. The treatment lasting for 60 minutes was
      applied for a period of 9 months, twice a week. Control group of 139 children
      were trained according to the program for preschool institutions. Treatment
      effects were assessed by 7 motor ability tests, one intellectual test (Raven's
      Colored Progressive Matrices) and 36-item questionnaire for assessing aberrant
      behavior, which was filled out by parents. Aberrant behavior reduced
      significantly when motor abilities improved through systematic exercise. These
      findings point to the importance of motor exercise and applying additional
      kinesiologic activities with various modalities to reduce aberrant behavior in
      preschool children.

PMID- 22397232
TI  - Effect of number of rooms and sibs on nutritional status among rural Bengalee
      preschool children from eastern India.
AB  - In developing countries including rural India, undernutrition among preschool
      children is one of the main barriers of the national development. However, there
      exists scanty information on the prevalence of underweight and stunting and their
      socio-demographic predictors among preschool children in India and West Bengal.
      The aim of the present study was to investigate the prevalence of underweight and
      stunting and the impact of two socio-demographic indicators, namely number of
      living rooms (NLR) and number of sibs (NS), on them among 1-5 year old Bengalee
      rural preschool children of Integrated Child Development Services (ICDS) Centres.
      This cross sectional study was undertaken at 30 randomly selected ICDS centre of
      Chapra Block, Nadia District, West Bengal, India. A total of 673 children, aged 1
      5 years were studied. The overall (age and sex combined) rates of underweight and
      stunting were 54.40% and 39.20%, respectively. NLR was significantly associated
      with the prevalence of underweight (chi2 = 4.34, df = 1, p < 0.05) and stunting
      (chi2 = 8.98, df = 1, p < 0.01) among girls. Similarly, NS had a significant
      association with prevalence of underweight (chi2 = 10.29, df = 1, p < 0.001) and
      stunting (chi2 = 5.42, df = 1, p < 0.05) among girls. Girls with < 2 NLR had
      significant higher risk of being underweight (OR = 1.64, C.I = 1.30-2.62) or
      stunted (OR=2.23, C.I = 1.31-3.80) than those with > or = 2 NLR. Moreover, girls
      with > or = 3 NS had significant higher rate of underweight (OR = 2.03, CI = 1.32
      3.146) or stunting (OR = 1.69, C.I = 1.09-2.63) than those with < 3 sibs.
      Logistic regression analyses also revealed that both NLR as well as NS were
      strong predictors of underweight (NLR: Wald = 4.30, p < 0.05; NS: Wald = 8.74, p
      < 0.001) and stunting (NLR: Wald = 10.17, p < 0.001; NS: Wald = 5.38, p < 0.05)
      among girls. Gender discrimination could be a likely cause for this sex
      difference in the impact of NRL and NS. Moreover, logistic regression were also
      undertaken with underweight and stunting status (yes/ no) as dependent variables
      and NLR and NS (combined) as independent variables to identify their effects,
      when considered together, on undernutrition. Results showed that NS had
      significant impact on underweight (Wald = 8.28, p < 0.001) rather than NLR among
      girls. Results also demonstrated that NLR had significant impact on stunting
      (Wald = 6.874, p < 0.01) rather than NS.

PMID- 22397233
TI  - School-age involvement in sport and perceived quality of sport services.
AB  - Creating an active and healthy lifestyle starts in infancy and adolescence. A
      number of individual and collective factors affect whether or not sport is taken
      up and continued, which is an essential element in achieving a healthy lifestyle
      in adolescence and extending this into adult life. This study sets out to
      determine the perceived quality of the sport service provided by schools with
      organised physical activities, and whether the most positively assessed public
      organisations have a higher percentage of participation than those with a more
      negative assessment. The study population was 1109 adolescents from 28 towns
      comprising part of a sport provision system. A self-devised questionnaire with
      all the necessary properties, validity and reliability was conducted. The results
      showed that 42% of the adolescents take part in organised physical sport, and
      give the service provided a positive assessment. It was found that in
      organisations with a more positive assessment, the town has a higher rate of
      involvement in sporting activities.

PMID- 22397234
TI  - Prevalence of nonspecific low back pain in schoolchildren in north-eastern
      Slovenia.
AB  - The aim of the study was to investigate the prevalence of the nonspecific low
      back pain (LBP) in a population of schoolchildren in Maribor, north-eastern
      Slovenia. 100 children from an elementary school (age 11-15 y) and 90 children
      from a secondary school (age 17-18 y) were included in the study and investigated
      with a structured Watson questionnaire to assess low back pain prevalence,
      symptom characteristics, psychosocial factors, demographic, and anthropometric
      items. The data was statistically analysed using the SPSS software. 43% of
      children from elementary schools and 44% of children from secondary schools
      experienced back pain which lasted more than one day. No correlations between LBP
      and anthropometric items were found. Schoolchildren spend approximately 2 hours
      for learning, 2-3 hours for watching TV and approximately 2 hours for playing or
      working with the computer. Among important reasons for LBP, 44% of children
      mentioned carrying a school bag, 28% sitting on school chairs, and 18% intensive
      sport activity. Clinical examination of cervical, thoracic, and lumbar spine has
      shown that 12% of primary children and 12% of secondary children have increased
      cervical lordosis and 15% of primary schoolchildren have increased lumbar
      lordosis. In 5% of schoolchildren we found mild spinal scoliotic changes. Among
      our schoolchildren sedentary behaviour and low physical activity dominate. LBP
      may have an impact on their daily life, therefore it is important to recognise
      and treat it as soon as possible.

PMID- 22397235
TI  - The study of athletes' body perception and gender role.
AB  - In this study, it has been aimed to examine athletes' body perception and gender
      role. 120 male athletes and 120 non-athletic male university students
      participated in the study voluntarily. In the study, as the data collecting
      means, The Multidimensional Body-Self Relations Questionnaire-MBSRQ was used in
      order to determine males' body perception levels, BEM Sex Role Inventory-BSRI was
      used to determine gender roles and Personal Information Form developed by the
      researcher was used to ascertain personal features of the subjects. When the
      athletes' body perception levels are examined, the features of physical
      competence orientation, health orientation, appearance evaluation, fitness
      evaluation, health evaluation and body areas satisfaction have been found to be
      higher than non-athletes' (p < 0.05). On the other hand; no difference has been
      found between athletes and non-athletes in terms of appearance orientation (p >
      0.05). When gender roles are examined, athletes have been found to have higher
      values than non-athletes' in terms of masculinity, femininity and social
      desirability (p < 0.05). To conclude; as well as considering sports as a factor
      increasing individuals' body perception level and gender role, it is also thought
      that athletes care about health, appearance and physical competence and are glad
      of body parts because of their muscled body structure developing due to the
      exercises and have flexible personality to show feminine and masculine features
      that the environment needs in terms of gender role.

PMID- 22397236
TI  - The effect of 8 week pilates exercise on body composition in obese women.
AB  - The objective of this study was to explore the effects of 8-weeks modern pilates
      mat and ball exercise program on body mass, waist circumference and waist to hip
      ratio on sedentary obese women total of 58 health sedentary obese women
      volunteered to participate in this study. They were divided randomly into 1 of 2
      groups: pilates training group (PTG; N = 34) and control group (CG; N = 27). A
      pilates training program was applied to the subjects one hour per day four days
      per week during 8 weeks. The subjects in the control group did not participate in
      the training and participated only in the pre and post test measurements. BMI,
      waist circumference, Waist-hip ratio, 4-site skinfold thickness (Biceps, Triceps,
      Supscapula and Iliac), fat percentage, resting metabolic rate, Lean body mass and
      flexibility were assessed before and after the pilates training program. The SPSS
      statistical program (version 16.0) was used for data analysis. Analyses of
      covariance (ANCOVAs) were run on each of the dependent variables. For all
      analyses, the criterion for significance was set at an alpha level of p < 0.05. 8
      weeks of pilates training program has been found to be effective on weight, Body
      mass index, Lean body mass, waist-hip ratio, biceps, triceps, fat percentage,
      basal metabolic rate, and flexibility in PTG (p < 0.05). The control group showed
      no significant differences in the same measures post-intervention. As a result
      there was a positive effect of Modern Pilates mat and ball exercises of reducing
      obesity, body composition parameters and flexibility at sedentary obese women.

PMID- 22397237
TI  - Hypertrophic cardiomyopathy and sudden cardiac death due to physical exercise in
      Croatia in a 27-year period.
AB  - The paper deals with the sudden cardiac death during physical exercise in males
      in Croatia. The data are a part of a retrospective study dealing with 69 sudden
      death due to physical activity in men in Croatia during 27 years: from January 1,
      1984 to December 31, 2010. Three of them suddenly died during training and two of
      them died during recreational physical exercise, probably because of malignant
      ventricular arrhythmia due to hyperthrophic cardiomyopathy. One had an
      obstructive form of hypertrophic cardiomyopathy with i.v. septum of 40 mm and
      four had a non-obstructive forms of hyperthrophic cardiomyopathy with left
      ventricular wall of 18-20-22-25 mm. First athlete was a short trails runner, aged
      24, with no any previous physical discomforts, who suddenly collapsed and died
      during training. The second athlete was a soccer player aged 18, with no any
      previous physical discomfort, who suddenly collapsed and died during training.
      The third aged 15, was a school boy, basketball player, with no any previous
      physical discomfort, who collapsed and died during training. Two aged 25 and 34,
      were with no physical discomfort during exercise and died suddenly during
      recreational soccer games. A sudden cardiac death due to physical exercise in
      young athletes in Croatia suffered of hyperthropic cardiomyopathy reached
      0.06/100 000 yearly (p = 0.00000) in 27 years, in teenagers 0.26/100 000 (p =
      0.00226), in teenagers suffered of hypertrophic cardiomyopathy reached 0.10/100
      000 (p = 0.00000), in all young athletes suffered of other heart diseases reached
      0.19/100 000 (p = 0.00005), and in the total male population aged 15 or more,
      engaged in sports and recreational physical exercise: 0.71/100.0000 (p =
      0.00001).

PMID- 22397238
TI  - The association of uric acid with glucose and lipids in general population:
      Croatian cross-sectional study.
AB  - Hyperuricemia may have an important role in metabolic syndrome, cardiovascular
      diseases and stroke. Elevated serum uric acid concentration has been shown to be
      the strong predictor of cardiovascular mortality in several recently published
      studies. Our aim was to determine the prevalence of hyperuricemia in general
      Croatian population and to investigate the association of serum uric acid with
      glucose and lipids. This was a retrospective cross-sectional study on 6,476
      consecutive adults. Prevalence of hyperuricemia was 13.9% in general population
      and it was significantly higher in males, than in females (26% vs. 6%; p <
      0.001). Median uric acid concentration was higher in males than in females (343
      vs. 238 micromol/L; p < 0.001). Age, glucose and lipid parameters did not
      correlate with uric acid. In hyperuricemic subjects, increased concentrations of
      glucose (33.1% vs. 13.1%; p < 0.001), triglycerides (46.9% vs. 17.6%; p < 0.001),
      total cholesterol (69.6% vs. 51.9%; p < 0.001), LDL-cholesterol (64.5% vs. 46.4%;
      p < 0.001) and decreased concentration of HDL-cholesterol (24.3% vs. 13.0%; p <
      0.001) were more prevalent than in subjects with normal serum concentrations of
      uric acid. Hyperuricemia is highly prevalent in Croatian general population and
      it aggregates with hyperglycemia and dyslipidemia.

PMID- 22397240
TI  - The prevalence of depression and anxiety in seafarers type 2 diabetic patients.
AB  - Depression and anxiety are co-morbid condition in diabetes as disease-related
      psychological reactions on this chronic metabolic illness. This study was aimed
      to determine the occurrence of depression and anxiety in seafarer's type 2
      diabetic patients. A random sample of 52 diabetic seafarers treated with diet and
      oral glucose lowering agents, and 56 healthy seafarers were screened for
      depression with The Beck Depression Inventory (BDI) and for anxiety with State
      Trait Anxiety Inventory (STAI 1, STAI 2). Depression (BDI > 18.5) and anxiety
      (STAI < 28.5) was significantly higher in the group of diabetic seafarers than in
      control group (more than 30%). Significant correlation was noted between
      depression and duration of diabetes mellitus, degree of obesity and poor
      glycaemic control (HbA1C > 8%) and longer duration of shipping routes (over 6
      months). The proportion of depression and anxiety was found higher in seafarer's
      type 2 diabetic patients than in the healthy seafarers.

PMID- 22397239
TI  - Effects of ramipril and valsartan on proteinuria and renal function in patients
      with nondiabetic proteinuria.
AB  - The renin-angiotensin system is involved in the progression of chronic renal
      disease of both diabetic and nondiabetic origin. The angiotensin-converting
      enzyme inhibitors and angiotensin II receptor blockers have been demonstrated to
      reduce urinary protein excretion and attenuate the development of renal injury.
      This prospective, randomized, 12-month study assessed the effects of ramipril (N
      = 23) vs. valsartan (N = 22) vs. combination of ramipril and valsartan (N = 26)
      on proteinuria, renal function and metabolic profile in 71 patients with
      nondiabetic proteinuria with normal or slightly impaired renal function.
      Monotherapy with ramipril or valsartan and combination of these two drugs
      significantly reduced proteinuria, serum creatinine, cholesterol and
      triglycerides as well as systolic and diastolic arterial blood pressure. There
      was no significant difference among three study groups according to reduction of
      arterial blood pressure, serum cholesterol and triglycerides. At one year, a
      significant reduction in serum creatinine was recorded in all three study groups,
      whereas at 3 and 6 months a statistically significant reduction in serum
      creatinine was only observed in patients on combination therapy. In addition, at
      3 months the reduction of proteinuria was significantly greater in patients on
      combination therapy than in those on either monotherapy. These results indicated
      the combination therapy with angiotensin-converting enzyme inhibitors and
      angiotensin II receptor blockers to be more efficacious than either monotherapy
      in reducing proteinuria and serum creatinine level in the first 3 (proteinuria
      and serum creatinine) or 6 (serum creatinine) months of treatment.

PMID- 22397241
TI  - Relationship between tumor vascularity and vascular endothelial growth factor as
      prognostic factors for patients with neuroblastoma.
AB  - Although the role of angiogenesis in tumor progression and response to treatment
      is generally well-characterized, for neuroblastomas clinical data regarding the
      contribution of angiogenesis and its predictive capacity remain unclear. The aim
      of this study was to evaluate whether tumor vascularity in the combination with
      expression of vascular endothelial growth factor (VEGF) represent prognostic
      factors for patients with neuroblastoma. Immunohistochemistry using anti-CD34 and
      anti-VEGF antibodies was used to analyze paraffin-embedded primary tumor tissues
      from 56 patients diagnosed with neuroblastoma. Tumor vascularity was estimated by
      calculating the tumor vascular volume fraction (TVVF), and VEGF expression was
      determined using semi-quantitative scoring. Statistical analyses including
      multivariate analysis were performed and compared with these two factors. Tumor
      vascularity had impact on survival of high VEGF expression neuroblastoma
      patients. Combination of high VEGF expression and TVVF value < or = 5% was
      independent predictor of overall survival (p-value = 0.0041, odds ratio (OR) (95%
      CI) = 8.67 (1.99-37.69) by the Cox proportional hazards model). This study
      revealed for the first time a group of extremely high-risk neuroblastoma with
      both high VEGF expression and poor vascularity. For these patients reduced rates
      of survival were observed (37% vs. 92.5%) (p < 0.0001). These patients did not
      experience a significant improvement following hematopoietic stem cell
      transplantation, and could be candidates for receiving novel therapies. These
      results indicate the importance of the mutual relationship between tumor
      vascularity and VEGF, because it gives better insight into the prognosis of
      patients with neuroblastoma.

PMID- 22397242
TI  - Analysis of anger expression style--continuous anger and personality types of
      professional soccer players.
AB  - The purpose of this study was to analyse the anger expression styles, the
      continuous anger and personality types of players who play football in the
      professional league. The research group consisted of 133 soccer players who are
      playing in sports teams in the Turkish Super League: Ankara Sport Club,
      Genclerbirligi Sports Club and Hacettepe Sports Club in the first league, Turk
      Telekom sports in the second league, and Kecioren Gucu Sports and Ankarademir
      Sports playing in the third league in the 2008-2009 football season. The Eysenck
      personality inventory was modified to Turkish by Bayar in 1983, having been
      developed by Eysenck and Eysenck in 1975 and the continuous anger-anger style
      scale (SOTO) was modified to Turkish by Ozer in 1994. The state trait anger scale
      (STAS) was originally developed by Spielberger in 1983. All these were used on
      soccer players participating in the study to determine the continuous anger and
      anger styles in this study. In the interpretation of data, a meaningfulness of p
      < 0.05, was applied by using regression analysis, the Kruskal Wallis Test, the
      one-way variance analysis (ANOVA) test and the Tukey test to find the differences
      among the groups. The SPSS (Statistical Package for Social Sciences) programme
      was used to find the accounted values and to evaluate the data. According to the
      results of this study, regarding the education level variable, while there was a
      meaningful difference between the continuous anger sub-dimension and anger
      control sub-dimension than continuous anger-anger expression styles, no
      significant difference was found among personality type sub-dimensions
      (psychoticism, extrovert, neurotic, false). In addition, a significant
      relationship was found between psychoticism, extrovert, neurotic, and lie sub
      dimensions and the personality type sub-dimensions of professional players'
      constant anger-anger expression styles.

PMID- 22397243
TI  - Are there any differences in power performance and morphological characteristics
      of Croatian adolescent soccer players according to the team position?
AB  - The aim of the study was to analyze differences in power performance and
      morphological characteristics of young Croatian soccer players with respect to
      their team positions and to establish correlations between the power performance
      variables. Anthropometric characteristics and jumping and sprint performances
      were analyzed for 45 soccer players (age 14-15; mean body height 175.4 +/- 6.61
      cm; body weight 63.6 +/- 8.06 kg) according to their team positions (defender,
      midfielder, forward). Pearsons coefficient of correlation was used to determine
      the relationship between the power performance variables. There were no
      significant differences (p > 0.05) in the power performance of players according
      to their team position. The only significant differences between players were in
      some of the anthropometric characteristics, such as height and weight linear
      relationship was determined between almost all the power performance variables.
      Since the players in this study were very young and their sports careers have not
      reached their peak performance, it is possible that their nominal team positions
      may change during their soccer careers.

PMID- 22397244
TI  - Differences in situation efficacy indicators at the elite basketball players that
      play on different positions in the team.
AB  - The aim of our study was to determine the differences in situational efficacy for
      basketball players, in relation to their team positions: between guards and
      forwards/centres, and between the players on the four major positions in the
      team. The final sample of subjects (74 basketball players) is selected from the
      initial sample of 107 subjects, selected from nine men's senior basketball teams
      that played in A-1 Croatian men's basketball league championship in 2006/2007.
      Results confirmed the hypothesis that there is a significant difference between
      different groups of players: point/shooting guards, comparing with
      forwards/centres; players that play on four positions: point guard, shooting
      guard, small forward, power forward/centre. Guards have shown greater efficiency
      and utilization of the three-point shots, while centres are better in two-point
      shots. Guards have a greater number of assists, successful and unsuccessful three
      point shots, while centres are better in the offensive and defensive rebounds, as
      same as in successful and unsuccessful two-point shots. No statistically
      significant differences were found among the players on the guard positions
      (point guard and shooting guard), while only one statistically significant
      difference is found among the players on the position forward/centre (small
      forward and power forward/centre).

PMID- 22397245
TI  - Differential diagnostic performance of Rose Bengal Score Test in Sjogren's
      syndrome patients.
AB  - Aim of the study was to evaluate the diagnostic performance of the Rose Bengal
      score test for Sjogren's syndrome (SS), and to explore differences between other
      tests and examinations. All participants were examined, including (but not
      limited to) unstimulated (UWS) and stimulated (SWS) whole saliva, labial gland
      biopsy (LGB or focus score), ophthalmologic questionnaire (ocular surface disease
      index OSDI) and objective tests: Schirmer test 1 (Sch. 1), Schirmer test 2
      (Sch.2), Tear Break-up Time (TBUT) test and Rose Bengal score (RBS). Data were
      analyzed using Mann Whitney U-test, Receiver Operating Characteristic analysis,
      with specificity and sensitivity calculations and Spearman's correlation test.
      ROC curves showed a poor diagnostic performance of TBUT and OSDI. Sch. 1, Sch.2
      and LGB all exhibited a high diagnostic performance. RBS exhibited the best
      performance (sensitivity 100,00; specificity 100,00; AUC 1,000). Study reveals
      the scarce reliability of TBUT, OSDI and Sch.1, and emphasizes RBS as the test of
      choice in the SS diagnosis.

PMID- 22397246
TI  - The ophthalmic anomalies in children with Down syndrome in Split-Dalmatian
      County.
AB  - Our aim was to present the ophthalmic anomalies in patients with Down syndrome in
      Split-Dalmatia County born from 1992 until 2009 year. It was a cross-sectional
      study. 153 children with Down syndrome aged 0-18 years from the Split-Dalmatia
      County were examined. One hundred twelve participants were borne in Split, 13 in
      Vrgorac,16 in Makarska, 12 in Sinj. All enrolled children underwent a complete
      ophthalmological examination (anterior segment, ocular motility, refractive
      status, fundus, measuring intraocular pressure (IOP). Of 89.5% percent of
      responders with refractive errors, 48.1% had myopia, 35.0% had hypermetropia,
      astygamtism in 16.7%, 28.7% strabismus, nystagmus (8.4%), cataracts (1.3%),
      glaucoma (1.9%), supernumerary optic disc vessels (24.1%) and keratoconus (1.3%).
      CONCLUSION: In patients with Down syndrome the prevalence of refractive errors
      (myopia prevalence), as well as other ophthalmological diseases was determined.

PMID- 22397247
TI  - Evaluation of hand asymmetry in relation to hand preference.
AB  - We evaluated the asymmetric hand measurements in right- and left-handed
      individuals. 343 men and 290 women aged 18-42 years (22.11 +/- 2.07) participated
      in the study. There were no statistically significant differences when right-left
      differences in hand length, third finger length, palmar length, and the digit
      index value were evaluated according to hand preference and sex. Statistically
      significant differences were found for right-left differences in hand width, hand
      shape index, and the palmar length/width according to hand preference. The strong
      left-handers, weak left-handers, and ambidextrous individuals in the study group
      all exhibited asymmetry favoring the left and were considered together.
      Similarly, the strong and weak right-handers exhibited asymmetry favoring the
      right hand and were considered together. The difference between these two groups
      was significant. When the data were evaluated according to sex, significant
      differences were found between the subgroups. In particular, right-left
      differences in the hand-shape index and palmar length/width values of the strong
      left-handers, weak left-handers, and ambidextrous individuals were found to be
      statistically significant according to sex; in contrast, the strong and weak
      right-handers showed no significant differences according to sex. These results
      suggest a relation of hand asymmetry to hand preference in a Turkish population.

PMID- 22397248
TI  - Lifestyle habits and the risk of head and neck cancer in Zagreb region.
AB  - In 2002, International Agency for Research on Cancer launched a multicentric case
      control study of head and neck cancer in 15 centres in 11 European countries,
      Croatia included. The Alcohol-related Cancers and Genetic Susceptibility in
      Europe (ARCAGE) study database with approximately 2500 case-control pairs is
      currently the largest head and neck cancer patients database in Europe. The aim
      of the present study was to estimate the risk of smoking and alcohol consumption
      in head and neck cancer patients from Zagreb region recruited in scope of the
      ARCAGE study. The cases (45 males, 9 females) and the controls (37 males, 9
      females) were recruited from University Hospital Dubrava and Merkur University
      Hospital. A blood sample and a lifestyle questionnaire were collected from all
      study subjects. Data were analysed by logistic regression analysis. The
      distribution of cases was: 43 oral, 9 pharyngeal and 2 laryngeal cancer cases.
      Ever-smokers had a 4-fold higher cancer risk (adjusted OR 4.3 (CI 1.20-15.4))
      compared to never-smokers. The adjusted odds ratio for alcohol consumption more
      than once a week was 4.1 (CI 1.5-11.2). The results are in keeping with
      previously published data from other countries.

PMID- 22397249
TI  - Most common skin tumours in correlation with solar ultraviolet radiation in the
      area of West Herzegovina.
AB  - Incidence rate of skin tumours, both, non-melanoma and melanoma, is increasing
      nowadays. Various etiological factors are of relevance for the occurrence of the
      diseases. The solar radiation, as well, long-term exposure to ultraviolet (UV)
      radiation, have the greatest impact on development of these skin tumours. Non
      melanoma skin tumours, Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma
      (SCC), are the most common skin tumours in humans, and usually develop on the
      chronically photo-exposed areas. As for the Malignant Melanoma (MM), one of the
      most aggressive skin tumours, the exposure to solar radiation also plays an
      important role. This study investigates the correlation between the skin tumours
      and UV radiation in the area of West Herzegovina, on the sample of 1676 patients.
      It presents the occurrence of skin tumours in the period from 1997 to 2003. The
      study investigates the incidence and the risk factors separately for every skin
      tumour which can be etiologically related to the occurrence of skin tumours and
      UV radiation: occupation, exposure to UV radiation, skin type, and family history
      on malignan tumours within the patient's family. The exact incidence rate of non
      melanoma and melanoma skin tumours in Bosnia and Herzegovina is still unknown,
      for the reason that the united National Cancer Register does not exist yet.

PMID- 22397250
TI  - An analysis of the pollution problem in Slavonski Brod (eastern Croatia).
AB  - H2S, PM2.5, O3, NO2, SO2 and meteorological parameters such as temperature,
      relative humidity, precipitation, wind speed and wind direction were measured
      simultaneously in an eastern Croatian town called Slavonski Brod during the
      season winter/spring 2010. Emissions from the nearby cross-border (Bosnia and
      Herzegovina) oil refinery were identified as sources of temporary elevated
      concentrations of H2S. The maximum daily averages of PM2.5 concentrations during
      the winter period were as high as 240 microg m(-3) which is a value 10 times
      greater than the threshold prescribed by the World Health Organization. It is
      considered that the heating season, dense traffic, intense industrial activities
      and temperature inversion during stable weather conditions are prevailing
      contributors to higher winter concentrations of PM2.5. The results of the
      principal component analysis technique (PCA) have shown that lower air
      temperature, lower wind speed and higher relative humidity play a significant
      role in the winter pollution episodes. From a public health point of view,
      implementation of measures aimed at reducing the levels of H2S and PM2.5 should
      be considered.

PMID- 22397251
TI  - Shunt in the diagnosis of initial lung lesion in smokers.
AB  - Cigarette smoking is an important risk factor for all respiratory tract diseases.
      Unfortunately, the symptoms develop slowly, thus patients feel the consequences
      of the slowly developing inflammation too late. The inflammation first develops
      in the area of respiratory bronchioles. In this stage, the disease is
      asymptomatic. The study included a sample of 31 smokers, mean age 36.38 years,
      with normal spirometry indices, acid-base status and arterial blood gases. The
      mean smoking index was 11.28 smoking/years. All subjects were healthy, without
      any subjective health problems or disease indicators. The aim was to define dead
      lung area (V/Q) as an early indicator of changes in smokers. Study results
      demonstrated the mean shunt value in smokers of 8.25%, which showed positive
      correlation with smoking. The shunt size yielded negative correlation with the
      forced expiratory volume in one second and midexpiratory flow in smokers. In
      conclusion, determination of lung shunt is a simple method that is sensitive
      enough in the diagnosis of initial lung lesion due to cigarette smoking.

PMID- 22397252
TI  - The influence of mother's active smoking during pregnancy on body mass index of
      newborns.
AB  - Many investigations have noted bad influence of smoking during pregnancy. In the
      present article, the influence of mothers smoking during pregnancy on the body
      mass index (BMI), birth weight and birth length are examined. This retrospective
      research included 219 children: Group I: 109 children from rural area of east
      Slavonia (born in General Hospital-Vinkovci) and group II: 110 children from
      industrial area (born in Zagreb). The questioned subjects were divided into two
      groups depending on mothers smoking during pregnancy: newborns of mothers who
      didn't smoke during pregnancy (subgroup A) and newborns of mother who did smoke
      10 or more cigarettes per day during pregnancy (subgroup B). Anthropometric
      parameters (BMI, birth length and birth weight) in newborns of non-smoking
      mothers were statistically higher (p < 0.05) than in newborns of smoking mothers.
      Moderate correlation between birth length and birth weight in newborns of non
      smoking and smoking mothers from rural area and from non-smoking mothers in urban
      area was statistically significant, but correlation in the group in newborns of
      smoking mothers from Zagreb was not statistically significant. Results of this
      research show that smoking during pregnancy significantly influences the birth
      weight and birth length. Further investigation is needed, to investigate the lack
      of correlation between the birth length and birth weight in newborns of smoking
      mothers from industrial city.

PMID- 22397253
TI  - Oxidative stress markers in patients with post-traumatic stress disorder.
AB  - Recent study data support the role of oxidative stress in diverse psychiatric
      disorders. Oxidative stress results from an oxidant/antioxidant imbalance, an
      excess of oxidants and/or a depletion of antioxidants. There are numerous studies
      that indicate that free radicals (FRs) damage neurons, and then play an important
      role in the pathophysiology of schizophrenia and depression. Active oxygen can
      cause considerable damage and disrupt the important physiological functions of
      proteins, lipids, enzymes and DNA. The aim of our study was to investigate the
      possible differences in the concentration of tromboxane B2, 8-OHdG and protein
      carbonyls, as significant markers of oxidative damage, and urate, albumin and
      total protein concentrations as antioxidative molecules in PTSD patients in
      comparison to the healthy control group. The study included 74 male participants
      who were active soldiers in the Croatian armed forces from 1991 to 1995. 46
      subjects with chronic and current PTSD were recruited from the Department of
      Psychiatry of Dubrava University Hospital during 2010, 28 healthy subjects were
      recruited in the same period during the regular medical examination at the
      Dubrava University Hospital. Study results have shown that there is no
      statistically significant difference in urinary concentrations of 8-OHdG, serum
      thromboxane B2, and serum urates between two studied groups. Statistically
      significant difference of the protein carbonyl concentrations was examined.
      Concentrations were significantly lower in the PTSD group than in the control
      group. The clinical significance of these results was examined using ROC
      analysis. The obtained ROC curves did not separate the groups in a satisfactory
      manner.

PMID- 22397254
TI  - Masticatory muscle and temporomandibular joint pain in Croatian war veterans with
      posttraumatic stress disorder.
AB  - The aim of this study was to investigate the prevalence and intensity of
      masticatory muscle and temporomandibular joint (TMJ) pain in Croatian war
      veterans with posttraumatic stress disorder (PTSD). The examined group consisted
      of 100 Croatian war veterans, in whom PTSD had previously been diagnosed.
      Patients were compared with 92 subjects who had not taken part in the war and in
      whom PTSD was excluded by psychiatric examination. The clinical examination
      consisted of palpation of the masticatory muscles, the prominent neck
      musculature, and TMJ. The examination technique used and the definition of items
      were previously tested for reliability and validity. 93% of the subjects with
      PTSD had masticatory muscle tenderness compared to 45.65% of the subjects in the
      control group (chi2 = 51.46, p < 0.0001). The most frequent painful location in
      the subjects with PTSD was the left lateral pterygoid site in 88%, and in
      subjects of the control group the right lateral pterygoid site in 28.26% of
      cases. The most painful location in the PTSD group was the left lateral pterygoid
      site in 72%, and in the control group the left posterior digastric in 4.35% of
      cases. 58% of the subjects with PTSD had TMJ tenderness compared to 3.26% of
      subjects in the control group (chi2 = 66.23, p < 0.0001). The most frequent
      painful location of TMJ in both groups was the left posterior capsule; in the
      PTSD group 38% and in subjects in the control group 2.17% of cases. The most
      painful location was the left posterior capsule in 28% of subjects with PTSD,
      while not one subject in the control group reported severe painful sensitivity.
      The very high frequency and intensity of pain in subjects with PTSD confirms the
      effect of stress on muscle and joint sensitivity, i.e. perception of pain.

PMID- 22397255
TI  - The impact of psychological testing on the patients suffering from
      stomatopyrosis.
AB  - Stomatopyrosis is commonly associated with stressful situations, which implies
      the importance of psychological conditions of the patients with this symptom.
      Patients suffering from burning mouth syndrome suffered from some psychical
      disturbances as well. The fact that depression and anxiety are closely connected
      with stomatopyrosis has been scientifically confirmed. The data which
      systematically led to this conclusion suggest the possibility of the existence of
      a psychogenic disturbance as an aetiological factor which leads to
      stomatopyrosis. Research which might be conducted in order to relate psychogenic
      disturbances with stomatopyrosis by means of various drugs and procedures, might
      provide an insight into the relatedness of these factors, which would enable us
      to treat the cause and not the consequence. This research has been directed
      towards establishing this "relatedness" by means of psychopharmatics and
      psychotherapy, and has been confirmed by means of psychological depression and
      anxiety tests. The research has been conducted on 120 respondents suffering from
      stomatopyrosis, who were also, as previously diagnosed, suffering from a
      psychical disturbance. The respondents were divided into 4 groups. Each group
      contained 30 respondents suffering from stomatopyrosis as the basic symptom, but
      with different psychogenic disturbances. These groups were: 1) antidepressants,
      2) anxiolytics, 3) autogenic training and 4) control group. A detailed clinical
      and psychiatric check-up was conducted before the treatment started, and was
      repeated several times in different intervals: after a month, after two months
      and after four months. Respondents are still undergoing a therapy. Subjective
      assessment of the intensity of the burning sensation was obtained according to
      Visual analogue scale and two psychological questionnaires (depression test and
      anxiety test). Conclusion is: 1) Antidepressants and anxiolytic drugs have a
      prominent role in the treatment of stomatopyrosis. Psychological tests conducted
      after a four-month period have shown improvement--there was a decrease in anxiety
      -7.5%-8.8%, while depression has in some of the tested groups completely
      disappeared. At the same time, subjective evaluation of the intensity of the
      symptom has, according to VAS, showed a fall from 6.93-7.8 cm to 2.13-3.0 cm. At
      the beginning of the treatment, symptoms were described as "pretty often" with
      36.7%-76.7% respondents, and as "permanent" with 23.3%-63.3% respondents. At the
      end of the treatment, the most frequent description regarding the frequency of
      the symptoms was "very rarely". 2) Autogenic training--psychotherapeutic
      anxiolytic technique--is the therapy of choice as far as stomatopyrosis is
      concerned, as it both eliminates the problems and emotionally rehabilitates the
      patient. 3) As far as the therapeutic progress is concerned, it can be taken as
      the "progress" of the time when the symptoms appear: during the treatment, the
      frequency and the duration of the symptoms have been shortened at night, while
      their occurrence during the day has been reported as relatively more frequent.

PMID- 22397256
TI  - Psychometric validation of the Croatian version of the Quality of Life in
      Epilepsy Inventory (QOLIE-31).
AB  - The primary goals of this study were to adapt the Quality of Life in Epilepsy
      Inventory-31 items (QOLIE-31) questionnaire to the Croatian language and to
      assess the translated questionnaire's psychometric properties.
      Translation/retranslation of the English version of the QOLIE-31 was done, and
      all steps for cross-cultural adaptation process were performed properly by an
      expert committee. Later, QOLIE-31 questionnaires and previously validated Short
      Form-36 (SF-36) outcome instruments were given to 200 patients with epilepsy. 172
      patients (86%) responded to the first set of questionnaires, and 114 of the first
      time respondents (66%) returned their second survey. The two measures of
      reliability as internal consistency and reproducibility were determined by
      Cronbach alpha statistics and intraclass correlation coefficient, respectively.
      Concurrent validity was measured by comparing with a SF-36 questionnaire, and
      measurement was made using the Pearson correlation coefficient (r). The study
      demonstrated satisfactory internal consistency with high Cronbach a values for
      all of the corresponding domains (seizure worry 0.84, medication effects 0.80,
      emotional well-being 0.73, energy/fatigue 0.76, cognitive functioning 0.71,
      social functioning 0.77, overall quality of life 0.65). The intraclass
      correlation coefficient for six domains of QOLIE-31 questionnaire demonstrated
      excellent test/retest reproducibility (ICC > or = 0.75), and good test/retest
      reproducibility (ICC 0.71) in one domain (cognitive functioning). Considering
      concurrent validity, three domains had excellent correlation (r = 0.75-1), while
      11 had good correlation (r = 0.50 to 0.75), and 3 had moderate correlation (r =
      0.25-0.50). This study demonstrated that, if measures are to be used across
      cultures, the items must not only be translated well linguistically but also must
      be culturally adapted to maintain the content validity of the instrument at a
      conceptual level across different cultures. Croatian version of QOLIE-31 will be
      a valuable contribution to outcome measurement in epilepsy patients, particularly
      in the context of treatment trials, but als in a wider research context.

PMID- 22397257
TI  - Assessment of stress level of forestry experts with academic education.
AB  - This paper provides the results of an applied research of forests engineers
      connected to their risk of mental stress occurrence in everyday work. This paper
      also has a component of a basic research, in which the adequacy and reliability
      of applied methodology in this kind of researches is examined. The mental stress
      induced risk is tested by usage of an e-mail survey which consists out of 23-part
      ERI (Effort-Reward Imbalance) questionnaire. For the assessment of mental stress
      exposure level following indicators have been used: 1) ERI--ratio of devoted
      effort and achieved reward, and 2) overcommitment. These indicators have been
      analyzed in comparison to the demographic parameters (gender, age) and the
      complexity of assigned jobs of the interviewees. The interview was applied on a
      randomly sampled forestry experts employed in public and private sector. The
      analysis of reliability of the three components of ERI questionnaire has showed
      satisfactory internal consistency. Descriptive statistics has been done regarding
      gender and the complexity of assigned jobs. The testing of the "devoted
      effort/achieved reward" variable (E/R index) has shown a statistically
      significant difference of the index value between male interviewees on managerial
      and standard expert positions. The value of E/R index was x > or = 1 at 18.97% of
      the sampled interviewees, which indicates a divergence between devoted effort and
      achieved reward, and also points to a possibility of mental stress occurrence
      risk. Multiple response tables have shown that female interviewees with less than
      20 years of professional experience manifest stress related symptoms earlier than
      their male colleagues with similar professional experience do. Regression
      analysis has shown a significant correlation of E/R index to gender, internship
      and overcommitment. This research also assesses the viability of the applied
      method as an instrument of forestry experts' mental stress level determination.

PMID- 22397258
TI  - Polycyclic aromatic hydrocarbons and heavy metals in Kostrena coastal area.
AB  - The aim of this study was to determine pollution by polycyclic aromatic
      hydrocarbons (PAH) and heavy metals in seawater and sediment in Kostrena coastal
      area, as well as their toxicity using bioluminescence based tests. Total PAH
      concentration in seawater ranged 1.7-155.3 ng/L. The share of carcinogenetic PAH
      was relatively high, ranging 22-48.3%. Nickel concentrations in seawater were
      beyond detection limits (< 0.1 microg/L), vanadium concentrations ranged 0.66
      1.96 microg/L, chrome concentrations were beyond detection limits, and copper
      concentrations were also beyond detection limits or extremely low (up to 0.32
      microg/L). EC50 values in seawater ranged 23.80-90.90 ng/L. Correlation between
      total PAH concentration and toxicity of seawater showed strong connection between
      them (r = 0.9579). Total PAH concentration in marine sediment ranged 58.02-1116
      microg/kg dry weight (d.w.). The share of carcinogenetic PAH was extremely high
      ranging 10-53%. Nickel concentrations in marine sediment ranged 8-24 mg/kg d.w.,
      vanadium concentrations ranged 24-42 mg/kg d.w., chrome concentrations ranged 11
      19 mg/kg d.w., and copper concentrations ranged 7-25 mg/kg d.w. EC50 values in
      marine sediment ranged 818-4596 microg/kg d.w. Correlation between total PAH
      concentration and toxicity of marine sediment showed weak connection between them
      (r = 0.2590). Previous studies of seawater samples from areas of the Adriatic sea
      under the direct influence of oil industry did not include concentrations of
      heavy metals, which makes our study the first to present such comprehensive
      results. Our results point out the need for further evaluations and following of
      marine environment pollution and its consequences on living organisms and marine
      ecosystem in whole.

PMID- 22397259
TI  - CT follow-up and clinical outcome in severe traumatic brain injury patients.
AB  - Determining a patient's prognosis after severe traumatic brain injury remains
      difficult and complex. The purpose of the present study was following up patients
      with severe traumatic brain injury by correlating their clinical outcome and
      sequential computer tomography (CT) findings. We investigated 51 patients who
      survived the first year following an accident. All patients underwent successive
      CT examinations within a maximum period of 2 years. The patients' outcomes
      depended on the underlying brain damage and are presented by the Glasgow Outcome
      Scale. Based on the investigated data we concluded that the worst outcomes were
      experienced by patients with initial massive cerebral edema, extensive subdural
      hematoma and intraventricular hemorrhage, followed by stroke as subacute CT
      finding and cerebral atrophy as chronic finding visible at follow-up CT scans.
      The majority of lesions identified by CT scan were found in the frontal lobes,
      basal ganglia, and temporal lobes. We suggest that CT examination still
      represents a simple and useful tool in attempting to predict the clinical outcome
      in patients with severe traumatic brain injury.

PMID- 22397260
TI  - Injuries of the tarsometatarsal joints: treatment and outcome.
AB  - Between January 2005 and May 2009, a total of 26 patients, 21 males and 5
      females, were admitted for treatment of Lisfranc lesion. All patients were
      radiologically evaluated and classified according to the criteria proposed by
      Myerson: 5 (19.2%) patients had a type A injury, 2 patients (7.7%) presented with
      a type B1 injury, 17 (65.4%) sustained the most common type B2 injury and 1
      (3.8%) patient suffered from a type C1 and C2 injury. Taking radiological and
      clinical findings in account, fifteen patients were elected for operative
      treatment and eleven patients were treated conservatively. According to type of
      fracture we established three groups; in group I metatarsal fracture was found in
      fourteen (53.9%) patients, group II with phalangeal fracture in three (11.5%)
      cases, whereas in group III nine (34.6%) patients sustained combined metatarsal,
      navicular and, most commonly, a cuneiform fracture. Using the American Orthopedic
      Foot and Ankle Society (AOFAS) midfoot scoring scale and SF-36 questionnaire, the
      functional outcome was assessed. The mean value for age distribution was 42.7 +/-
      13.2 years and the mean follow up was 27.9 +/- 12.4 months. A p value < 0.005 was
      regarded as statistically significant for the analysis of the results. We found
      by means of SF 36 questionnaire a statistically significant difference in the
      role limitation due to existence of pain (p = 0.04) and poor general health (p =
      0.013) in the group of patients that sustained combined foot fracture. The
      purpose of this study is to assess the treatment of Lisfranc injuries in our
      patients, according to SF36 and AOFAS criteria, clinical outcome was evaluated.
      In the group I the mean AOFAS score was 74.0 +/- 9.1 and in the group II it
      reached 72.0 +/- 5.2 signifying fair outcome! Poor outcome was present in the
      group III with mean AOFAS score 67.1 +/- 9.0. All unstable injuries require
      surgery. Clinical outcome is highly dependent on the restoration of normal
      anatomic alignment.

PMID- 22397262
TI  - Functional outcome assessment of lower limb amputees and prosthetic users with a
      2-minute walk test.
AB  - The aim of this study was to assess the functional outcome of a population of
      lower limb amputees supplied with prosthesis. The research was conducted from
      June to September of 2010 at the Center for Physical and Rehabilitation Medicine,
      of the Clinical Hospital Center Rijeka, Croatia. The study included 50 adult
      subjects of both genders with a unilateral transtibial or transfemoral lower limb
      amputations. The 2-minute walk test (2MWT) was used to assess the functional
      outcome of these individuals. Data were statistically analyzed. Subjects were
      divided into groups according to age. The best results were obtained by subjects
      between the age of 45 and 59 years. The difference between groups was
      statistically significant (p < 0.001). Taking into account the cause of
      amputation, there was a statistically significant difference in the results of
      the 2 MWT between subjects in whom the cause of amputation was circulatory and
      those where the cause of the amputation was not due to circulatory problems. The
      best results were obtained in subjects in whom the cause of amputation was not
      circulatory (p = 0.009). Considering the level of amputation there was a
      statistically significant difference in the results of the 2MWT between subjects
      with transtibial and those with transfemoral amputations. Better results were
      obtained in transtibial amputees (p = 0.039). Considering the first prosthetic
      supply, better results were obtained in subjects using prosthetic devices over 9
      years (p = 0.031). Our research confirmed that age, gender, level and cause of
      amputation, including the time from the first prosthetic supply have an effect on
      the 2MWT results.

PMID- 22397261
TI  - Peripheral regional analgesia with femoral catheter versus intravenous patient
      controlled analgesia after total knee arthroplasty: a prospective randomized
      study.
AB  - The aim of this study is to compare the effects of femoral analgesia (FA) with
      0.25% levobupivacain and intravenous patient controlled analgesia (PCA) with
      morphine on postoperative pain assessed by a visual-analog scale (VAS) score and
      their complications during the first 24 postoperative hours after the a total
      knee arthroplasty in a prospective randomized study. Secondary outcomes included:
      morphine use, patient satisfaction, complication of analgesia and duration of
      hospital stay. We analyzed 71 patients with an ASA score of II or III. The
      patients were randomized into two groups: group PCA (n = 36) was given the PCA
      pump, which contained morphine; and group FA (n = 35) was given first a bolus
      dose, then a continuous infusion 0.25% levobupivacain via a femoral catheter. The
      assessment of VAS was performed every 2 hours. There were no differences between
      the PCA and FA groups regarding demographic characteristics, operation duration,
      ASA score distribution, duration of hospital stay and satisfaction with analgesia
      (although there were more satisfied patients in the FA group). Significant
      differences were noted in the quantity of morphine used (higher values were in
      the PCA group; p < 0.001). More complications were recorded in PCA group (p <
      0.001). The VAS score was lower in the FA group (p < 0.001). The highest
      difference occurred 4 hours after the operation, with the PCA group having
      significantly higher VAS score values compared to the FA group. Femoral analgesia
      leads to a stronger pain relief with less side effects, less morphine use and
      more patient satisfaction than intravenous PCA with morphine.

PMID- 22397263
TI  - A tetrahydrophthalazine derivative 'sodium nucleinate" exerts a potent
      suppressive effect upon LPS-stimulated mononuclear cells in vitro and in vivo.
AB  - We described the use of a new chemical substance Sodium nucleinate (SN) as an
      immunomodulatory substance exhibiting antiinflammatory properties. Sodium
      nucleinate (SN) registrated in Russian Federation as Tamerit, is 2-amino-1,2,3,4
      tetrahydrophthalazine-1,4-dione sodium salt dihydrate, derivative of well known
      chemical substance luminol. To comprehend the mechanisms of SN immunomodulatory
      activity, we examined the SN modulation of the innate inflammatory cytokine
      response of human PBMC stimulated with LPS in vitro. Furthermore, we studied the
      immunomodulatory effects of SN in mice challenged with E. coli LPS in vivo to
      investigate a possible novel approach to therapy of excessive inflammation that
      interfere with the response to endotoxin and inflammatory mediators. Our results
      demonstrated that SN is an efficient inhibitor of sepsis development in mice
      model of LPS-induced sepsis. The changes induced by SN include decreased mice
      plasma inflammatory cytokine production. Simmilary we demonstrated a decreased
      TNF-alpha, IFN-gamma and IL-6 response in human LPS-stimulated PBMNCs. SN was
      therefore shown to be a promising inhibitor of multiple inflammatory cytokine
      secretion.

PMID- 22397265
TI  - Monitoring the presence of genetically modified food on the market of the
      Republic of Croatia.
AB  - From the beginning of the human race people have been applying different methods
      to change the genetic material of either plants or animals in order to increase
      their yield as well as to improve the quality and quantity of food. Genetically
      modified organism (GMO) means an organism in which the genetic material has been
      altered in a way that does not occur naturally by mating and/or natural
      recombination. Analysing the presence of GMO in food is done by detecting the
      presence of either specific DNA sequences inserted in the genome of transgenic
      organism, or detecting proteins as a result of the expression of the inserted
      DNA. In this work food testing for the presence of genetically modified organisms
      was conducted during the period from 2004 to 2007 in the GMO laboratory of the
      Croatian National Institute of Public Health. According to the regulations, among
      the samples in which the presence of GMO was detected, all those which had more
      than 0.9% of GMO content were either rejected from the border or removed from the
      market, because such GM food has to be appropriately labelled. Among the food
      samples which were analysed in 2004: 127 (2.37%) of a total of 1226 samples
      contained more than 0.9% of GMOs; in 2005 there was only one in 512 (0.20%)
      samples in total; in 2006 there were 4 out of 404 samples (0.99%), and in 2007: 7
      of a total of 655 samples (1.07%) had GMO content above the allowed threshold of
      0.9%.

PMID- 22397264
TI  - The use of a food supplementation with D-phenylalanine, L-glutamine and L-5
      hydroxytriptophan in the alleviation of alcohol withdrawal symptoms.
AB  - We described the use of a food supplementation with D-phenylalanine, L-glutamine
      and L-5-hydroxytriptophan in the alleviation of alcohol withdrawal symptoms in
      patients starting a detoxification therapy. Since abstinence from ethanol causes
      a hypodopaminergic and a hypoopioidergic environment in the reword system
      circuits, manifesting with withdrawal symptoms, food supplements that contains D
      phenylalanine a peptidase inhibitor (of opioide inactivation) and L-amino-acids
      (for dopamine synthesis) were used to replenish a lack in neurotransmitters and
      alleviate the symptoms of alcohol withdrawal. 20 patients suffering from alcohol
      addictions starting a detoxification therapy have been included in a prospective,
      randomized, double blind study. The patients have been randomly devided in two
      groups. One group recieved for a period of 40 days a food supplement containing D
      phenylalanine, L-glutamine and L-5-hydroxytriptophan (investigation group), and
      the control (placebo) group. On the first day of hospitalization the patients
      performed a SCL-90-R test, and blood samples were taken for measuring liver
      enzymes, total bilirubin, unbound cortisol and lymphocyte populations. The same
      was done on the 40th day of hospitalization. During the therapy a significant
      decrease in SCL-90-R psychiatric symptoms scores and a significant increase in
      CD4 lymphocyte count was observed in the investigation group. The cortisol values
      were significantly, but equally decreased in both groups, the same was with the
      liver enzymes and the total bilirubin values. We conclude that abstinence causes
      a major stress for the patients. The use of food supplement containing D
      phenylalanine, L-glutamine and L-5-hydroxytriptophan alleviates the withdrawal
      symptoms and causes a rise in CD4 lymphocyte population, but it dose not affect
      the serum cortisol levels, which are probably more affected by liver inflammation
      and the liver restitution.

PMID- 22397266
TI  - The effect of demographic characteristics on self-medication patterns: a cross
      sectional nationwide study from Slovenia.
AB  - Self-medication is defined as the use of medicines without medical supervision to
      treat one's own ailment. It is apart of a help-seeking behaviour that depends on
      socio-cultural and personal factors, which is why people react to the illness
      differently and also take different measures to cope with it. The aim of this
      study was to explore the Slovenian citizens' attitudes towards self-medication.
      The study included a random sample of 1,000 Slovenian inhabitants, stratified to
      all Slovenian regions. This was a postal survey. Participants were mailed a self
      administered questionnaire about attitudes towards self-treatment. In the
      statistical analysis we used independent t-test and chi2-test. We received 410
      responses (41.0% response rate). In the past year, 389 (94.9%) respondents
      practiced self-medication. Most respondents (209, 52.1%) supported and used it in
      everyday life. The majority of the respondents (274, 77.2%) practiced self
      medication when symptoms emerged. When symptoms lasted for one week or less, 210
      (56.5%) of the respondents practising self-medication visited their doctor. The
      respondents agreed mostly with the statement that their doctor had a positive
      relationship towards self-medication. Younger people were more confident about
      the absolute safety of self-medication whereas older people were more certain
      that they could practice it no matter what disease they might have. As self
      medication is very common among Slovenian population and various demographic
      factors affect the opinions about it and the reasons for its use and also a
      doctor-patients communication about it, it is important that doctors, especially
      those in primary health care settings always ask about its use. This is of a
      particular importance when dealing with older and retired patients, which are
      more likely to suffer from more chronic diseases and use alternative medicine,
      which is a common part of self-medication. Also, it is important to educate young
      people about possible unsafe practice of self-medication.

PMID- 22397267
TI  - The distribution of HLA alleles among children with atopic asthma in Croatia.
AB  - Allergic asthma is a multifactorial disease involving well known environmental
      factors and less identified genetic components. In several studies the HLA genes
      have been implicated in the development of asthma and atopy, but the importance
      of these associations remains unclear. The aim of the present study was to
      analyse the distribution of specificities at HLA class I loci (-A and -B) and HLA
      class II locus (-DRB1) in a group of 143 Croatian children with atopic asthma,
      regarding total serum IgE and specific IgE against common inhalant allergens, as
      well as their connection with different asthmatic phenotypes and to identify HLA
      genotype which increases the risk for atopy or asthma or which has a protective
      effect. As controls we used a group of 163 healthy unrelated individuals. HLA
      class I antigens were determined by serology, while DRB1 specificities were
      detected by polymerase-chain reaction amplification and hybridisation with
      sequence specific oligonucleotide probes method (PCR-SSOP). We found no
      significant correlation between any of the HLA-A antigens and asthma, atopy or
      associated atopic phenotypes. At HLA-B locus, HLA-B8 antigen was significantly
      increased among asthmatic patients (p = 0.002), patients with high total serum
      IgE (p = 0.002), as well as among patients sensitizated to Dermatophagoides
      pteronyssinus (Der p) (p = 0.014) and among patients sensitizated to Der p +
      Dactylis glomerata (Dact g) or Ambrosia elatior (Amb a) (p = 0.004). Among HLA
      DRB1 specificities, HLA-DRB1 *01 showed positive correlation with asthma and
      atopy (p = 0.034), while HLA-DRB1*03 specificity was observed with significantly
      higher frequency among patients with total serum IgE > or = 400 KU/L (p = 0.048).
      HLA-DRB1*16 specificity was observed with significantly lower frequency among
      patients with asthma only in comparison to healthy controls (p = 0.027) and to
      patients with asthma and allergic rhinitis (p = 0.005). In conclusion, our data
      suggest that HLA specificities play a relevant role in predisposition to asthma,
      as well as in different clinical forms of atopic diseases. HLA-B8, HLA-DRB1*01
      and HLA-DRB1*03 genotype increases the risk for atopic asthma and high serum IgE.

PMID- 22397268
TI  - Consanguinity in two Spanish regions: La Cabrera and Fuentes Carrionas.
      Dispensations and isonymy.
AB  - In this work the level and structure of consanguinity is analysed in two Spanish
      rural regions of similar geographic and orographic characteristics for the period
      between 1880 and 1979, employing two different methodologies. The estimates
      according dispensations shows that the total levels (alpha4 = 0.00552 in La
      Cabrera and 0.00405 in Fuentes Carrionas) and the structures of consanguinity
      (C22/C33 = 0.43 and 0.34) are similar in both regions, but have evolved
      differently. Whereas in La Cabrera both parameters have remained stable, in
      Fuentes Carrionas they fluctuated through the period analysed. On studying the
      structure of consanguinity more closely using the isonymic method, it can be seen
      that in La Cabrera total consanguinity (Ft = 0.0206) should be attributed mainly
      to environmental factors (Fr = 0.0193) and to a lesser extent to socio-cultural
      factors (Fn = 0.0013), whereas in Fuentes Carrionas it derives, almost
      exclusively, from the former (Ft = 0.01270; Fr = 0.01589; Fn = -0.00325).

PMID- 22397269
TI  - Effect of electromagnetic radiofrequency radiation on the rats' brain, liver and
      kidney cells measured by comet assay.
AB  - The goal of study was to evaluate DNA damage in rat's renal, liver and brain
      cells after in vivo exposure to radiofrequency/microwave (Rf/Mw) radiation of
      cellular phone frequencies range. To determine DNA damage, a single cell gel
      electrophoresis/comet assay was used. Wistar rats (male, 12 week old, approximate
      body weight 350 g) (N = 9) were exposed to the carrier frequency of 915 MHz with
      Global System Mobile signal modulation (GSM), power density of 2.4 W/m2, whole
      body average specific absorption rate SAR of 0.6 W/kg. The animals were
      irradiated for one hour/day, seven days/week during two weeks period. The
      exposure set-up was Gigahertz Transversal Electromagnetic Mode Cell (GTEM--cell).
      Sham irradiated controls (N = 9) were apart of the study. The body temperature
      was measured before and after exposure. There were no differences in temperature
      in between control and treated animals. Comet assay parameters such as the tail
      length and tail intensity were evaluated. In comparison with tail length in
      controls (13.5 +/- 0.7 microm), the tail was slightly elongated in brain cells of
      irradiated animals (14.0 +/- 0.3 microm). The tail length obtained for liver
      (14.5 +/- 0.3 microm) and kidney (13.9 +/- 0.5 microm) homogenates notably
      differs in comparison with matched sham controls (13.6 +/- 0.3 microm) and (12.9
      +/- 0.9 microm). Differences in tail intensity between control and exposed
      animals were not significant. The results of this study suggest that, under the
      experimental conditions applied, repeated 915 MHz irradiation could be a cause of
      DNA breaks in renal and liver cells, but not affect the cell genome at the higher
      extent compared to the basal damage.

PMID- 22397270
TI  - Valdoltra and osteoarticular tuberculosis among Slovenians--the 100th anniversary
      of the Valdoltra Hospital.
AB  - The 100th anniversary of the hospital in Valdoltra, Slovenia, on the northeastern
      Adriatic coast near the Italian frontier--where borders have frequently changed
      (the town has belonged to Austria-Hungary, Italy, Yugoslavia, and Slovenia) and
      which experienced military occupation in the interwar period--offers an
      opportunity to review the professional path of this institution. The hospital was
      established in 1909 as an act of charity by the Trieste Friends of Children
      Society due to the high incidence of scrofula as well as bone and extrapulmonary
      tuberculosis among Trieste children. With 270 beds, it provided medical
      assistance to sick children and also later to adults. After the First World War,
      its management was assumed by the Italian Red Cross, which built an additional
      wing in 1934 and increased the hospital's capacity to 340 beds. After Italy's
      capitulation, German soldiers occupied the hospital and left it in shambles at
      the end of the war. In September 1945, the hospital was renovated and taken over
      by the Slovenian healthcare system; 400 beds were again available for treating
      bone tuberculosis patients. This did not last for long. By 1947, after the Treaty
      of Peace with Italy was signed and Valdoltra became the central Yugoslav
      institution for treating bone tuberculosis, the hospital had to be relocated to
      Rovinj, Croatia due to the political division of the Trieste region into Zones A
      and B. Only in 1952 did the hospital return to Valdoltra and continue its
      mission. In the twentieth century, tuberculosis was treated similarly everywhere
      until antitubercular agents were discovered. At first, conservative climatic and
      hygiene-dietary methods, orthopedic aids, plaster corsets, and physiotherapy were
      used to treat bone tuberculosis. This was followed by surgical treatment, which
      came into vogue after 1945, when it was supported by antibiotic treatment, and
      (postoperative) physiotherapy and rehabilitation. Chemotherapeutic agents and
      preventive outpatient BCG-vaccination proved successful in curing bone
      tuberculosis and other forms of tuberculosis, and the number of consumptive
      patients continued to decrease. The Valdoltra hospital has preserved its
      tradition of treating osteoarticular pathologies and has been the main Slovenian
      orthopedic hospital since 1961.

PMID- 22397271
TI  - Guidelines for the structure of methodological processes in visual anthropology.
AB  - Vast majority of visual anthropologists of the 20th century were more focused on
      general phenomenology of visual anthropology, i.e. the content aspect of their
      works and their impact on scientific knowledge, leaving behind style of directing
      and practical principles & processes of creating anthropological film. So far,
      judging by the available literature, there are no strict guidelines for
      directorial procedures, nor the precise definition of determining of the
      methodical processes in production of an anthropological film. Consequently, the
      goal of this study is to determine the structure and forms of methodical
      processes as well as to define the advantages and disadvantages of each of them.
      By using adequate guidelines, the researcher, i.e. the author of the
      anthropological film, can optimize the production and post-production processes
      as soon as in preparation (preproduction) period of working on the film, by the
      technical choice of the approach to the production
      (proactive/reactive/subjective/objective...) and by defining the style of
      directing. In other words, it ultimately means more relevant scientific research
      result with less time and resources.

PMID- 22397272
TI  - MRI study of the ACL in children and adolescents.
AB  - Reconstruction of the ACL (anterior cruciate ligament) requires precise
      anatomical placement of the tendon graft. Anatomic variations may
      increase/decrease risk of the ACL rupture. Twenty-eight children with clinical,
      MRI and arthroscopic verified ACL ruptures were compared with match case control
      group. MRI was done one to 12 months after trauma. The thresholds values for
      identifying the ACL rupture were set; ACL angle < 45 degrees, Blumensat angle > 0
      degrees, and the PCL angle < 115 degrees. RESULTS: There was no significant
      difference of tibial attachment for the ACL and measured parameters of the femur.
      The ACL angle (p < 0.001), the Blumensat angle (p = 0.001), and the PCL angle (p
      < 0.001) were significantly different. Each of the patients in group with a torn
      ACL had at least one parameter positive. DISCUSSION: ACL angle, Blumensat angle
      and PCL angle might help to diagnose ruptured ACL. Pediatric patients with the
      ruptured ACL show no difference in notch width or the tibial roof inclination
      angle as compared with pediatric patients without ACL rupture.

PMID- 22397273
TI  - Quality of life in children after cardiac surgery for congenital heart disease.
AB  - The aim of this study was to assess the quality of life children after cardiac
      surgery for congenital heart disease (CHD) and to compare these results with
      healthy children. To assess the quality of life children after surgery for CHD we
      performed a cross-sectional study of 114 patients who were patients at the
      Department of Paediatrics in Tuzla, between the ages of 2 and 18 years, of both
      sexes, and with one of their parents. We used the "PedsQL 4.0 Generic Core
      Scales", with both child self-report and parent proxy-reports. By self
      assessment, the PedsQL total scores for quality of life were statistically
      significantly different between children after cardiac surgery for ages 13 to 18
      years and healthy children, while by parent report PedsQL total scores were
      statistically significantly different between children after cardiac surgery for
      ages 5 to 7 years and healthy children. By self assessment, children after
      cardiac surgery for ages from 5 to 7 and 13 to 18 years reported that they have a
      statistically significantly lower quality of life in the segment school
      functioning compared to the healthy children. By parental assessment, children
      after cardiac surgery for ages 2 to 4, 5 to 7 and 8 to 12 years have a
      statistically significantly lower quality of life in the segments of physical and
      psychosocial health, emotional, social and school functioning. The results of our
      study indicate that children after cardiac surgery for CHD by self and parent
      assessment have a lower quality of life than healthy children.

PMID- 22397274
TI  - Dilemma of antiepileptic drugs withdrawal in symptomatic epilepsy.
AB  - A successful treatment of epilepsy depends on numerous factors such as etiology,
      genetics and environmental impact. An exact diagnosis, treatment and an adequate
      selection of antiepileptic drugs (AED) are important from the very beginning. The
      patient with symptomatic epilepsy caused by the brain tumor (low-grade
      astrocytoma in the left parietal lobe, surgically removed 17 years after the
      first manifestation of illness) is presented in this study. He has been seizure
      free for 6 years. The represented case study deals with the risk-benefit analysis
      of the discontinuation of the prescribed antiepileptic treatment that has lasted
      for 23 years.

PMID- 22397275
TI  - Reconstruction of a soft tissue defect of the back after myelomeningocele closure
      with modified V-Y plasty.
AB  - Myelomeningocele is a congenital defect in vertebral arches with cystic
      dilatation of meninges and structural or functional abnormality of spinal cord or
      cauda equina. It is a form of spinal dysraphisam with overlying skin defect
      (spina bifida aperta). That condition is related to other clinical complications
      such as infection that can produce furthermore complications. To prevent rate of
      complications surgical treatment in first 24 h is strongly suggested. In this
      case report we describe a patient (infant) with congenital myelomeningocele who's
      defect was treated surgically by the neurosurgeon. In operative procedure plastic
      surgeon was involved to cover the skin defect remaining after neurosurgical
      closure of spinal canal. Bilateral advancement local skin flaps were used in soft
      tissue defect closure. Review of the literature that refers to advancement local
      skin flaps was carried out.

PMID- 22397276
TI  - Torsion of epiploic appendage mimic acute appendicitis.
AB  - Epiploic appendagitis is a rare cause of focal abdominal pain which, depending on
      its localisation, can mimic a variety of abdominal diseases. We report a case of
      36-year-old woman who presented with a classic signs of acute appendicitis. On
      examination, the obese, afebrile, and had very strong right iliac fossa
      tenderness and guarding. The white cell count was 12.82 x 10(9)/L, and C reactive
      protein count was 15.13MG/DL. She underwent emergency laparoscopic procedure
      after the acute appendicitis diagnosis has been established. Laparoscopic
      exploration of the abdominal cavity showed vermiform, no inflamed, appendix and
      necrotic appendix epiploica of the caecum. The treatment consisted of typical
      laparoscopic appendectomy and laparoscopic resection of the necrotic appendix
      epiploica. The patient made rapid recovery and was discharged from the hospital
      on second day after the operation. Histological investigation of the appendix
      epiploica revealed gangrenous epiploic appendage.

PMID- 22397277
TI  - Endoscopically assisted latissimus dorsi flap harvesting and breast
      reconstruction in young female with Poland syndrome.
AB  - We will describe a second phase of breast reconstruction on a young girl
      suffering from Poland syndrome. She has the breast, pectoralis major and minor
      muscle aplasia on the right side. She has no other deformities. The best result
      is achieved by combining latissimus dorsi flap and a silicone implant, and even
      better aesthetic result is accomplished with endoscopically assisted latissimus
      dorsi harvesting. Purpose of this operation is to correct the chest asymmetry and
      to accomplish good aesthetic result.

PMID- 22397278
TI  - Isolated splenic metastasis from colorectal carcinoma in a high risk patient: a
      case report.
AB  - Isolated splenic metastasis arising from a colorectal carcinoma is a rare
      finding. We report a case of 74-year-old man with a medical history of diabetes
      type II and paroxysmal atrial fibrillation, who underwent a right hemicolectomy
      for an adenocarcinoma of caecum in August 2004. In June 2007 the patient was
      diagnosed with high grade aortic valve stenosis as well as long segment stenosis
      of the first obtuse marginal branch of left coronary artery. He was suggested
      aortic valve replacement with coronary artery bypass grafting but he refused the
      surgery. In October 2007 the patient underwent alpha 18FDG - PET scanning, due to
      increasing values of CEA serum level, which showed a 5 cm big isolated
      hypermetabolic lesion in the spleen. Due to operative risk, splenectomy was
      refused by surgeons. The patient underwent a chemotherapy with capecitabine in
      total of 8 cycles before his CEA level began to rise and MSCT showed a
      progression in size of splenic metastasis. The patients condition was reevaluated
      by a team of experts and splenectomy was performed in September 2008. In May 2009
      during the postoperative follow up, MSCT scanning revealed enlarged lymph nodes
      in celiac region and hepatic lesion suspicious of metastasis and the patient was
      admitted for further chemotherapy treatment. There is still no standardized
      treatment for this condition due to small number of cases reported in literature.
      Splenectomy followed by chemotherapy seems to be an optimal treatment but still
      no final conclusions can be made.

PMID- 22397279
TI  - Cystic echinococcosis of lung and heart coupled with repeated echinococcosis of
      brain--a case report.
AB  - Echinococcosis is rarely encountered as a cystic brain disease. In this article
      we are presenting a case of a young woman repeatedly operated due to
      echinococcosis of lung, heart and brain. Recurrent brain ecchinococcosis
      developed despite preoperative and postoperative albendazol therapy after first
      and combined therapy with albendazol and praziquantel after the second brain
      surgery. The mechanism of recurrence remains unclear (primary infestation,
      dissemination after spontaneous or intraoperative cyst rupture or new
      infestation).

PMID- 22397280
TI  - Bracelet creases among twins.
AB  - Bracelet creases among the twins were examined. A total of 42 pairs of twins
      (monozygotic twins-16 pairs, dizygotic like sex twins-20 pairs and dizygotic
      unlike sex twins-6 pairs) from the states of West Bengal and Madhya Pradesh of
      India were studied for this purpose. High discordance value in dizygotic twins in
      various types of bracelet creases is found to be sufficient to account for the
      high estimates of heritability. Estimated value of heritability (0.80), however,
      corroborates this finding. This is indicative of major role played by genetic
      factors in the expression of the trait as compared to environmental factors.

PMID- 22397281
TI  - The jubilees of the discovery of insulin & glycemic index: where conventional
      meets complementary medicine in the management of diabetes mellitus.
AB  - This year we marked two important jubilees in the management of diabetes
      mellitus: one is the discovery of insulin 90 years ago and the other one is the
      introduction of the Glycemic Index, 60 years later, both originated at the
      University of Toronto, Canada. Both discoveries can help to improve diabetes
      tremendously and thus have contributed to the advancement of management of this
      troubling disease the incidence of which continues to climb at a staggering rate.

PMID- 22397282
TI  - Effects of body mass index on adolescents' social comparisons and body cathexis
      in Istanbul.
AB  - This descriptive-comparative study was carried out to examine the relationship
      between the distribution of body mass index (BMI) values and scores on the Social
      Comparison Scale (SCS) and the Body Cathexis Scale (BCS). The study was carried
      out among 373 randomly selected students who were currently studying at a
      government private high school (N = 208) or a public high school (N = 165)
      located in Istanbul, the largest city in Turkey. The students' BMI percentile
      ranges were compared with scores on the BCS and SCS. Data from the study were
      evaluated statistically by percentages, means, t-tests, tests of analysis of
      variance (ANOVA), and the Kruskall-Wallis test. The mean age (in years) of the
      participating adolescents was 16.1 +/- 0.8. In all, 61% of the participating
      students were male (N = 227), 45% were attending 10th grade (N = 169), and 56% (N
      = 208) were attending a government private high school. The great majority
      (92.5%) of the adolescents had a BMI between the 5th and 95th percentiles (5th to
      < 85th is normal; 85th to < 95th is overweight or at risk for obesity). The
      Cronbach's alpha coefficient was 0.93 for the BCS and 0.83 for the SCS. Judging
      from this study, social comparison and satisfaction with one's body are not
      related to BMI among Turkish adolescents. Also according to this study, female
      Turkish adolescents are more satisfied with their body image than are their male
      counterparts.

PMID- 22397283
TI  - Known symptoms and diseases of a number of classical European composers during
      17th and 20th century in relation with their artistic musical expressions.
AB  - Medical history and relationship to the medical conditions as well as to the
      music creativity and productivity of some of the classical European composers
      have been described. In this review article we analyzed their illnesses as well
      as association between physical or mental diseases and their creativity and
      adaptability to disease. Some classical composers suffered from organic diseases,
      while others complained of mental disturbances. However, in spite of their
      disorders, the intensity of their creativity mostly remained unchanged.

PMID- 22397284
TI  - Alzheimer's dementia: current data review.
AB  - The review focuses on current data on Alzhemier's dementia, a clinical syndrom
      characterised with acquired deterioration of cognitive functioning and emotional
      capacities, which impaires everyday activity and quality of life. Alzheimer's
      dementia is the most common type of dementia in clinical surveys. The diagnosis
      of Alzheimer's dementia is primarily based on symptoms and signs and memory
      impairment is clinically most significant. Cholinesterase inhibitors -donepezil,
      rivastigmine and galantamine are considered to be the first line pharmacotherapy
      for mild to moderate Alzheimer's disease. Currently, no effective pharmacologic
      interventions have been researched enough to support their use in prevention of
      Alzheimer's dementia. Studies suggest that healthy lifestyle, ongoing education,
      regular physical activity, and cholesterol control, play a role in prevention of
      Alzheimer's dementia.

PMID- 22397285
TI  - Restless legs syndrome.
AB  - Being of the most frequent causes of insomnia, which in the end leads to chronic
      fatigue, inadequate performance of daily activities, and serious disruption of
      quality of living, restless legs syndrome (RLS) is nowadays not only a serious
      medical problem but a socio-economical one as well. Prevalence of the disorder in
      general population is estimated at 5 to 15%. Family history is positive in over
      50% of idiopathic RLS patients which points to genetic basis of the disorder. The
      characteristics of the secondary or acquired form of RLS are symptoms that start
      later in life as well as a rapid progression of the disease. On the other hand,
      idiopathic RLS more often starts at a younger age and the prognoses are better.
      Over twenty disorders and conditions are brought in connection with secondary
      RLS. Although the cause of primary RLS is still unknown, there is a strong
      connection between central metabolism of iron as well as dopamine levels and RLS
      manifestation. A differential diagnosis of RLS includes a wide specter of motor
      and sensory disorders. Diagnosis is based on clinical features and the history of
      disease. To correctly diagnose idiopathic RLS one must first eliminate secondary
      causes of RLS and then also exclude any disorders with clinical features that
      mimic those of RLS. It has been estimated that some 20 to 25% of patients need
      pharmacological therapy. Best initial therapy is the application of nonergot
      dopamine agonists. Anticonvulsants, benzodiazepines and opioides can be given to
      patients who are refractory to dopaminergic therapy, those suffering from RLS
      with emphasized painful sensory component and those with RLS connected with
      insomnia.

PMID- 22397286
TI  - Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CS)
      as treatment of peritoneal carcinomatosis: preliminary results in Croatia.
AB  - The purpose of our study was to evaluate initial results following introduction
      of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Cytoreductive Surgery
      (CS). Twenty two patients with intraperitoneal malignancy undergone cytoreductive
      surgery (CS) and hyperthermic intraoperative chemotherapy (HIPEC) between January
      of 2007 and January 2010. Nine patients had adenocarcinoma of colorectal origin,
      8 patients had ovarian cancer, and 5 had pseudomyxoma peritonei. Inclusion
      criteria were diagnosis of peritoneal carcinomatosis based on intraoperative
      assessment during first operative procedure for intraabdominal malignancy or
      follow-up diagnostic imaging proof Excluded were patients with known malignant
      proliferation outside abdomen, liver metastasis and ASA score 4 and higher. All
      patients with pseudomyxoma peritonei diagnosis are alive, with mean follow-up
      time 24.8 months (range 15-35). In group of patients with adenocarcinoma from
      colorectal origin, 3 died, resulting in mean survival time 7.6 months (range 1
      16). In group of patients with ovarian cancer, 2 died, resulting in mean survival
      time 13.8 months (range 0-31). Two patients died in early postoperative period.
      Most of the patients had some sort of mental disorder. Although HIPEC with CS
      improves survival, during introduction period higher morbidity and mortality
      could be expected.

PMID- 22397287
TI  - Position of intragastric balloons in global initiative for obesity treatment.
AB  - Obesity is chronic disease with multiple health consequences and among the most
      severe health problems worldwide. According to public health records around 65%
      of population in Croatia are overweight and 20% obese. National physicians
      chamber with support of Health and Social Welfare Ministry gave recommendations
      on diagnosing and treating of obesity in form of national consensus. Treatment of
      obesity is complex and enrolls multiple clinical specialties. Change of life
      style, strenuous physical activity and pharmacotherapy are part of conservative
      treatments. Patients are treated more efficiently by minimally invasive
      endoscopic procedures or bariatric surgery depending on starting body mass index
      score. Implantation of intragastric balloons is conceptually simple method of
      obesity treatment. Modern devices as Bio-Enterics intragastric balloons (BIB),
      (Inamed Health, USA) are gaining wide popularity among both patients and
      physicians. BIB intragastric offers the best gains with individuals ranging BMI
      from 35 to 40. Efficiency has relative timeline dependance from 85% at 6 months
      to 24% at 36 months. BIB offers substantial ameliorative influence on obesity
      comorbidities, particularly cardiovascular risk. Treatment with BIB is also
      efficient but transient treatment modality in morbidly and superobese individuals
      to reduce preoperative risks of general and bariatric surgery. Obesity treatment
      with BIB is well tolerated and safe, offering better quality of life.
      Nevertheless, due to relative poor results of conservative obesity treatments on
      long-term follow up further investigations defining new clinical parameters for
      solving treatment resistance. In order to provide resourcefully individualized
      approach modern perspectives are focused on endocrine constitutes of obesity.
      Hormonal effects of BIB treatment in compare to bariatric surgery are potentially
      interesting for the prospect studies.

PMID- 22397289
TI  - The new year--new challenges.

PMID- 22397288
TI  - Glycemic index in diabetes.
AB  - The Glycemic Index (GI) is a rating system that ranks carbohydrate-containing
      foods according to their postprandial blood glucose response relative to the same
      quantity of available carbohydrate of a standard such as white bread or glucose.
      The concept of GI was first introduced in the early 80's by Jenkins and
      coworkers. Since then, numerous trials have been undertaken, many indicating
      benefits of a low GI diet on glycemic control, as well as lipid profiles, insulin
      and C-peptide levels, inflammatory and thrombolytic factors, endothelial function
      and regulation of body weight. As a result, a low-GI diet may prevent or delay
      the vascular complications of diabetes. However, despite many studies supporting
      the benefits of the Glycemic Index as part of the treatment of diabetes mellitus,
      several areas of controversy have been raised in the literature and are addressed
      here. Clinicians treating diabetic patients should be aware of the potential
      benefits of low-GI foods in the prevention and treatment of diabetes and its
      complications.

PMID- 22397290
TI  - [Reduction of juvenile obesity by programmed physical exercise and controlled
      diet].
AB  - BACKGROUND/AIM: Obesity is the most common disease of nutrition and is the
      consequence of reduced movement. Unfortunately, this problem is increasingly
      present in juvenile age, so that the pediatric outpatient offices are dominated
      by obese young people. The aim of this study was to evaluate and quantify the
      effects of the reducing treatment for juvenile obesity conducted by programmed
      physical exercise and controlled diet. METHODS: We tested a sample of 136
      respondents of both sexes (76 girls and 60 boys) aged 13 +/- 0.6 years. This
      prospective study took 3 months in 2007 using the experimental methods of
      longitudinal weather precision. The data obtained after the measurement were
      processed by the use of statistical programs to calculate the basic and
      dispersion parameters. To determine the difference between the initial and final
      measurements we applied the univariate analysis of variance (ANOVA) and
      differences in the variables system in the space were determined by multivariate
      analysis of variance (MANOVA). RESULTS: The results of ANOVA in the form of F
      values indicated that the differences between the initial and final measurements
      in all parameters of circumference dimensionality and subcutaneous fat tissue are
      significant (p = 0.00). Also, differences in parameters of body constitution and
      indicators of alimentation showed a high statistical significance (p = 0.00). The
      results of multivariante analysis (MANOVA), using Wilk's Lambda test, also
      indicated that the differences between initial and final measurements in the area
      of anthropometric measures and indicators of alimentation and constitution, were
      statistically significant (p = 0.00). CONCLUSION: Application of physical
      exercise and controlled diet leads to a significant reduction of anthropometric
      parameters and anthropological indicators of alimentation.

PMID- 22397291
TI  - [Significance of proper oral hygiene for health condition of mouth and teeth].
AB  - BACKGROUND/AIM: Proper mouth and teeth hygiene has influence on the prevention of
      a great number of diseases and very often some of them are not related only to
      oral cavity. Most frequent diseases of mouth and teeth such as caries and
      periodontal diseases are caused, among other factors, by poor oral hygiene. They
      are also more frequent in young population. The aim of this study was to estimate
      the influence of sociodemographic characteristics and hygienic habit on oral
      health in children aged 11-15 years. METHODS: This cross-sectional study was
      conducted by the dental teams in dentist surgeries in Tivat Health Center between
      May and September 2009. The sample consisted of patients 11 to 15 years of age. A
      questionnaire and dental examination of mouth and teeth were used as research
      instruments. The examinations were conducted in accordance with the World Health
      Organization methodology and criteria. The data obtained from the interviews were
      correlated with those obtained from the clinical examinations. RESULTS: The
      results show that the majority of respondents brush their teeth twice a day and
      visit the dentist once in every six months. The research also shows that 57%
      respondents have caries of deciduous teeth and over 63% respondents of permanent
      teeth. Gingivitis was found in 14% and orthodontic anomalies in 44.7%
      respondents. A half of respondents who brush their teeth rarely have problems
      with gingivitis. There is a highly statistically significant difference between
      the occurrence of gingivitis and the frequency of teeth brushing. CONCLUSION:
      There is a significant difference between mouth and oral hygiene and sex as well
      as other sociodemographic characteristics of respondents. The study showed the
      correlation between occurrence of caries and the gingivitis and frequency of
      teeth brushing and dental visits.

PMID- 22397292
TI  - [Evaluation of coagulation factors in fresh frozen plasma treated with riboflavin
      and ultraviolet light].
AB  - BACKGROUND/AIM: Pathogen inactivation in blood products using riboflavin and
      ultraviolet (UV) light represents a proactive approach to blood safety, not only
      for known infectious agents but also for new ones or not yet recognized as
      threats to the blood supply. This method inactivates a virus, bacteria, fungus,
      or protozoan pathogen from the blood product without damaging its function or
      shelf-life. The aim of the study was to study the influence of photoinactivation
      using riboflavin on the concentration of coagulation factors and coagulation
      inhibitors in plasma that was treated before freezing. METHODS: The examination
      included 30 units of plasma, separated from whole blood donated by voluntary
      blood donors around 6 h from the moment of collection. They were treated by
      riboflavin (35 mL) and UV rays (6.24 J/mL, 265-370 nm) on Mirasol aparature
      (Caridian BCT Biotechnologies, USA) in approximate duration of 6 min. The samples
      for examining were taken before (K - control units) and after illumination (I -
      illuminated units). RESULTS: Comparing the middle values of coagulation factors
      in the control and illuminated units we noticed their statistically significant
      decrease in illuminated units (p < 0.001), but the activity of coagulation ones
      was still in the reference range. The most sensitive coagulation factors to
      photoinactivation were FVIII, FIX and FXI (21.99%, 20.54% and 17.26% loss,
      respectively). Anticoagulant factors were better preseved than coagulation
      factors. CONCLUSION: Plasma separated from whole blood donation within 6 h,
      treated with riboflavin and UV light within 6 h from separation and frozen at
      temperature below -30 degrees C within 24 h, shows good retention of pro- and
      anticoagulation activity.

PMID- 22397293
TI  - [Postoperative nonlethal complications following open heart surgery].
AB  - BACKGROUND/AIM: Postoperative nonlethal complications after open heart surgery
      are a serious clinical problem causing a considerable engagement of health
      workers, an augmented use of drugs, and prolonged operation incapac ity leading
      to prolonged hospital stay and increased expenses. The aim of the study was to
      establish whether there is any correlation between the level of expected
      operative risk and postoperative nonlethal complications. METHODS: A consecutive
      series of 853 patients subjected to the open heart surgery were investigated, 622
      (73%) males and 231 (27%) females. The average age of the patients was 57.2 +/-
      9.9 (16-81) years. The patients were divided into 3 groups according to the
      additive EuroSCORE model: groups I, II and III with the expected operative risk
      of 0%-2%, 2%-5% and over 5%, respectively. The data were collected prospectively
      and analyzed retrospectively. Statistical methods of correlation and t-test were
      used. RESULTS: A high degree of correlation between the operative risk level and
      frequency of postoperative nonlethal complications (R = 0.98) was found. The
      average rate of complications was 24% for the whole group of 853 patients. It
      accounted for 21%, 29% and 47% in the groups I, II and III, respectively.
      According to the expected operative risk level there was a statistically
      significant difference in respect of heart arrhythmias (p = 0.02), neurologic
      complications (p = 0.002), and pulmonary complications (p = 0.009). CONCLUSION:
      Our results show a high degree of correlation between the expected level of
      operative risk according to the EuroSCORE model and the frequency of
      postoperative nonlethal complications. There is a statistically significant
      difference in respect to frequency of heart rhythm disturbances, pulmonary and
      neurological complications and expected operative mortality.

PMID- 22397294
TI  - Left ventricular noncompaction: clinical-echocardiographic study.
AB  - BACKGROUND/AIM: Left ventricular noncompaction (LVNC) is a disorder in
      endomyocardial morphogenesis, seen either isolated (in the absence of other
      cardiac anomalies) or in association with congenital heart disease and some
      neuromuscular diseases. Intrauterine arrest of the compaction of myocardial
      fibers is postulated to be the reason of LVNC. Recognition of this condition is
      extremely important due to its high mortality and morbidity that lead to
      progressive heart failure, ventricular arrhythmias and thromboembolic events. The
      aim of this study was to determine the prevalence and clinical presentation of
      LVNC among consecutive outpatients according to clinical and echocardiographyic
      findings. METHOD: A total of 3,854 consecutive patients examined at the Institute
      for Cardiovascular Diseases within a period January 2006 - January 2007 were
      included in the study. All the patients underwent echocardiographic examination
      using the same equipment (Vivid 7, GE Medical System). Echocardiographic
      parameters and clinical presentation in patients with echocardiographic criteria
      for LVNC were analyzed. RESULTS: Analyzing 3,854 consecutive outpatients, using
      two-dimensional Color Doppler echocardiography from January 2006 to January 2007,
      12 patients met the criteria for LVNC. Seven of them were male. The mean age at
      diagnosis was 45 +/- 15 years. Analyzing clinical manifestation of LVNC it was
      found that seven patients had signs of heart failure, six had arrhythmias with no
      embolic events. CONCLUSION: Our results suggest that the real prevalence of LVNC
      may be higher than expected. New studies have to be done to solve this problem.

PMID- 22397295
TI  - Allogeneic stem cell transplant for chronic myeloid leukemia as a still promising
      option in the era of the new target therapy.
AB  - BACKGROUND/AIM: Introducing tyrosine kinase inhibitors (TKIs) has essentially
      changed curative approach, to be precise, clearly improved treatment efficacy for
      chronic myeloid leukemia (CML). Thus, the place and usage of allogeneic stem cell
      transplant (SCT) in CML treatment--as a former "nearly monopolistic" therapeutic
      manner--is nowadays controversial. The objective of this retrospective study was
      to evaluate the results obtained in the treatment of CML patients, with a
      particular attempt to define parameters critical for clinical benefit and
      superior overall outcome following allogeneic SCT. METHODS: A total of 32 CML
      patients (27 in chronic phase and 5 with advanced disease), with female/male
      ratio 11/21, aged from 9 to 54 (32 in average) years, underwent allogeneic SCTs
      (1993 to 2009). The initial treatment for 25 patients was interferon alpha (IFN
      alpha) with or without ARA-C, and additional 7 patients with no response to
      imatinib mesylat (IM). The time from diagnosis to SCT was approximately 12 (range
      3-37) months. The patient were categorized according to the risk for the disease,
      transplant-related mortality (TRM) scoring system, and stem cell (SC) source. The
      basic conditioning regimen was a combination of busulphan and cyclophosphamide
      (BuCy-2). Graft-versus-host disease (GvHD) was typically prevented with
      cyclosporine-A (CsA) and methotrexate (MTX). RESULTS: Engraftment was observed in
      26 (84.4%) patients, with polymorphonuclear (PMNs) and platelet (Plt) recovery on
      the 15th (range 10-22) and 19th (range 11-29) posttranspalnt days, respectively.
      Acute GvHD (aGvHD) had 13/26 (50%), and chronic GvHD (cGvHD) 10/21 (47.1%)
      patients. The incidence of overall TRM was 46.8% (15/32), while early death was
      noticed in 4 (12.5%) patients. A cause of death in 9 (28.1%) patients was cGvHD,
      in 2 (6.25%) patients infection, and in 3 (9.35%) cases disease-relapse was
      occurred. Fourteen (43.7%) of the patients are still alive, 9 from the low-risk
      group for TRM, with long-term survival from 1 to 16 years. Patients who received
      SCs from peripheral blood (PB) vs bone marrow (BM) had significantly faster
      engraftment (p < 0.05), lower oropharingeal mucositis rate (25% vs 70%; p <
      0.05), but more frequent cGvHD (83.3% vs 30.3%; p < 0.05). A significantly
      improved (log-rank = 2.39; p < 0.01) overall survival (OS) was obtained in BM
      setting. CONCLUSION: The results obtained in this study are in accordance with
      data from analogous clinical trials. Exactly, in the era of the new target
      therapy (TKI application), allogeneic SCT can be still a convenient therapeutic
      approach for well-selected CML-patients, especially for those with initial high
      risk disease and lower probability of TRM.

PMID- 22397297
TI  - Attitudes and motives of potential sperm donors in Serbia.
AB  - BACKGROUND/AIM: For curing infertility, sperm donors and their donations are
      important source of benefits for the society. Attitudes of sperm donors towards
      different recipient categories and relation with offspring become more important.
      The aim of our study was to explore sperm donation related attitudes and motives
      among potential sperm donors in Serbia. METHODS: The study included 303
      participants from Serbia, age from 20 to 40. Measures of personality traits were
      obtained by using the Big Five Inventory. For measuring attitudes and motivation
      regarding sperm donation the Attitudes and Motivation of Sperm Donors
      questionnaire was applied. RESULTS: A total of 244 participants stated that they
      would be willing to be sperm donors. The results showed no statistically
      significant differences in personality traits between people who claimed that
      they would be willing to become sperm donors, and those claiming otherwise, but a
      number of differences in personality traits were found when various attitudes
      regarding sperm donation process, possible users of donated sperm and relations
      between the donor and his biological offspring were considered. CONCLUSION: There
      are no statistically significant differences in personality traits between people
      who claimed that they would and those that would not be willing to become sperm
      donors. It is possible that some other factors (e.g. cultural values) influence
      the decision to become sperm donor, but personality traits play an important role
      in making decisions regarding sperm donation process, possible receivers of
      donation and relations between the donor and his biological offspring.

PMID- 22397296
TI  - [HIV/AIDS and other sexually transmitted infections among military members of the
      Armed Forces of Serbia].
AB  - BACKGROUND/AIM: Military personnel is a population group at special risk of
      exposure to sexually transmitted diseases (STD). In peacetime, STD infection
      rates among service members are generally 2 to 5 times higher than among civilian
      population. In time of conflict, the differences can be 50 or more times greater.
      This study describes sexual behavior as a risk factor for STD in the Armed Forces
      of Serbia. METHODS: The sample of 5 617 voluntary blood donors from the Armed
      Forces of Serbia gave blood and filled World Health Organization Questionnaire
      about sexual behavior within January 2007 - December 2008 period. The mandatory
      testing of voluntary blood donors was performed in the Institute of
      Transfusiology Military Medical Academy in Belgrade, by the specific immunoenzyme
      tests and polymerasa chain reaction tests for HIV, hepatitis B, C and syphilis.
      Statistical analysis of data was done using State for Windows 93, USA, 1996.
      RESULTS: We identified 36 soldiers with some form of STDs. This study showed that
      1 668 (29.7%) tested soldiers reported always using condoms, 1 725 (30.72%)
      almost always, 1 238 (20.04%) sometimes, 495 (8.81%) almost never and 490 (8.73%)
      never. Among the sample, 449 (7.99%) soldiers reported sexual contacts with
      partners with high risk of sexual behavior, whilst 22 (0.37%) of them reported
      homosexual and bisexual contacts. CONCLUSION: This study reported STDs found in
      voluntary blood donors among the service members of the Armed Forces of Serbia,
      but none of them was identified to be HIV positive. Soldiers with the most
      frequent risk behavior were reported to be those with inconsistent condom use. In
      the future, the STD Control and Prevention Program should be more intensively
      conducted among the members of the Armed Forces of Serbia.

PMID- 22397298
TI  - [New aspects of sepsis pathophysiology in critically ill].

PMID- 22397299
TI  - [Interleukin-33/ST2: a new signaling pathway in immunity and immunopathology].

PMID- 22397300
TI  - [The long-term remission of rheumatoid arthritis with a single cycle of
      rituximab].
AB  - INTRODUCTION: Rituximab selectively targets CD20+ B cells and presumably protects
      joints in rheumatoid arthritis. Complete remissions after a single treatment with
      rituximab, in some cases for longer than 1 year, are observed in only the
      minority of patients. We reported a patient suffering from refractory rheumatoid
      arthritis who responded to rituximab with sustained remission. CASE REPORT: A 78
      year-old woman was diagnosed with seropositive rheumatoid arthritis in 2001. The
      disease remained active despite conventional disease modifying drugs. In February
      2007 the disease was highly active. Two infusions of rituximab 1 000 mg on days 1
      and 15 were performed. Concomitant treatment consisted of metotrexate 10 mg/week
      and prednisolone 5 mg/day. The patients were assessed every month after receiving
      rituximab. Remission was achieved three months later. The patient was retreated
      with a second cycle of rituximab in December 2009 due to arthritic flare.
      CONCLUSION: This case report showed that the rituximab treatment was feasible and
      led to a clinically relevant and long lasting improvement in disease activity.

PMID- 22397301
TI  - Application of radiovisiography (digital radiology) in dental clinical practice.
AB  - INTRODUCTION: Radiovisiography (RVG) as the latest imaging technique in dentistry
      with the minimal radiation exposure of the patient and numerous possibilities to
      process the images has many advantages over classic radiography. CASE REPORT: We
      presented an interesting clinical endodontic case of primary posted diagnosis of
      traumatic periodontitis of upper right canine upon orthodontics treatment. As the
      patient previously had been exposed to alleged high dose of radiation the patient
      agreed to minimal exposition using digital RVG. The options of the tool bar of
      RVG Trophy device enabled the solving of ethiologic factor of presented
      periodontitis. The enigma of the symptoms on the 'overfilled' root canal was
      solved zooming and 3-D analysis avoiding periapical surgery owing to the patience
      of the patient and the dentist in a couple of days. CONCLUSION: By applying RVG
      technique the time for diagnostic procedure is much shorter in comparison with
      traditional dental radiography enabling archiving and follow-up the presented
      case in the course of time.

PMID- 22397302
TI  - Idiopathic polypoidal choroidal vasculopathy.
AB  - BACKGROUND: Idiopathic polypoidal choroidal vasculopathy (IPCV) is uncommon
      condition. It is considered to be a variant of neovascular age-related macular
      degeneration, but it can be also found in younger patients. CASE REPORT: We
      presented a case of otherwise healthy, 36-year-old women, with sudden unilateral
      visual impairment in the left eye and metamorphosia. Slit lamp biomicroscopy
      examination of the eye anterior segment was normal. Intraocular pressure
      determined by aplanation tonometry was 16 mmHg in both eyes. Indirect slit lamp
      biomicroscopy examination showed signs of serosanquinous detachments of the
      retinal pigment epithelium. Fluorescein angiography showed a subretinal vessel
      network through the pigment epithelial atrophy with hyperfluorescence in superior
      part of serohemorrhagic pigment epithelial detachment and the inferior
      hypofluorescence, caused by hemorrhage. Optical coherence tomography proved
      detachment of the retinal pigment epithelium. CONCLUSION: In patients with IPCV a
      mild, natural course with spontaneous resorption of exudations and hemorrhage and
      improvement in visual acuity can be observed. There is no approved treatment at
      present.

PMID- 22397303
TI  - [Elective reconstruction of thoracoabdominal aortic aneurysm type IV by
      transabdominal approach].
AB  - INTRODUCTION: Thoracoabdominal aortic aneurysm (TAAA) type IV represents an
      aortic dilatation from the level of the diaphragmatic hiatus to the iliac
      arteries branches, including visceral branches of the aorta. In the traditional
      procedure of TAAA type IV repair, the body is opened using thoractomy and
      laparotomy in order to provide adequate exposure of the descending thoracic and
      abdominal aorta for safe aortic reconstruction. CASE REPORT: We reported a 71
      year-old man with elective reconstruction of the TAAA type IV performed by
      transabdominal approach. Computed tomography scans angiography revealed a TAAA
      type IV with diameter of 62 mm in the region of celiac trunk andsuperior
      mesenteric artery branching, and the largest diameter of 75 mm in the infrarenal
      aortic level. The patient comorbidity included a chronic obstructive pulmonary
      disease and hypertension, therefore he was treated for a prolonged period. In
      preparation for the planned aortic reconstruction asymptomatic carotid disease
      (occlusion of the left internal carotid artery and subtotal stenosis of the right
      internal carotid artery) was diagnosed. Within the same intervention percutaneous
      transluminal angioplasty with stent placement in right internal carotid artery
      was made. In general, under endotracheal anesthesia and epidural analgesia, with
      transabdominal approach performed aortic reconstruction with tubular dakron graft
      24 mm were, and reimplantation of visceral aortic branches into the graft
      performed. Postoperative course was uneventful, and the patient was discharged on
      the postoperative day 17. Control computed tomography scan angiography performed
      three months after the operation showed vascular state of the patient to be in
      order. CONCLUSION: Complete transabdominal approach to TAAA type IV represents an
      appropriate substitute for thoracoabdominal approach, without compromising safety
      of the patient. This approach is less traumatic, especially in patients with
      impaired pulmonary function, because there is no thoracotomy and any
      complications that could follow this approach.

PMID- 22397304
TI  - Traumatic experiences, psychophysical consequences and needs of human trafficking
      victims.

PMID- 22397305
TI  - Report on the 13th European AIDS Conference/EACS.

PMID- 22397306
TI  - Computational prediction of residues involved in fidelity checking for DNA
      synthesis in DNA polymerase I.
AB  - Recent single-molecule Forster resonance energy transfer studies of DNA
      polymerase I have led to the proposal of a postinsertion fidelity-checking site.
      This site is hypothesized to ensure proper base pairing of the newly inserted
      nucleotide. To help test this hypothesis, we have used energy decomposition,
      electrostatic free energy response, and noncovalent interaction analysis analyses
      to identify residues involved in this putative checking site. We have used
      structures of DNA polymerase I from two different organisms, the Klenow fragment
      from Escherichia coli and the Bacillus fragment from Bacillus stearothermophilus.
      Our results point to several residues that show altered interactions for three
      mispairs compared to the correctly paired DNA dimer. Furthermore, many of these
      residues are conserved among A family polymerases. The identified residues
      provide potential targets for mutagenesis studies for investigation of the
      fidelity-checking site hypothesis.

PMID- 22397307
TI  - Cost of clinical management of acromegaly in Spain.
AB  - INTRODUCTION AND BACKGROUND: The cost of the therapeutic management of acromegaly
      depends on the selection of resources used, surgery and/or pharmacological
      treatment, by the specialist responsible for treatment, related to the
      characteristics of the patient and tumour. The objective of this work is to
      evaluate these costs for an illness that is rare but that is associated with a
      high morbidity in the context of routine clinical practice. METHODS: This was an
      epidemiological, prospective, naturalistic, multicentre study in Spain, in which
      38 endocrinologists participated. Adult patients with acromegaly and a pituitary
      microadenoma or macroadenoma were included in the study. Patients were assigned,
      according to first-line treatment, to the following two groups: surgery first
      line group (surgery in the 6 months before inclusion or during the follow-up
      period) and pharmaceutical first-line group (treatment with somatostatin
      analogues [SAs] for at least 6 months and with or without surgery after starting
      treatment with SAs). Data were collected during routine visits made during a
      follow-up period of 2 years. All resources were estimated at 2009 prices (?) and
      adjusted according to the Spanish consumer price index in 2010. RESULTS: Seventy
      four patients were included, the majority of them with macroadenoma (70%). Eighty
      eight percent of patients were treated surgically (76% as a first-line
      treatment), while 12% of patients received only SAs. Treatment with SAs was used
      at some point in the study by 85% of patients. The mean annual total cost of
      acromegaly is ?9668 per patient (?9223 for the surgery group and ?11,054 for the
      pharmaceutical group). Seventy-one percent of the direct cost of the disease
      corresponds to treatment with SAs. The cost of a patient treated only with
      surgery is ?2501 on an annual basis, versus ?9745 for a patient receiving only
      pharmacological treatment. In cases where a combination of both types of
      treatment is required, the annual total cost ranges from ?10,866 to ?12,364.
      CONCLUSION: The annual direct cost per patients of acromegaly in Spain is ?9668.
      Even though surgery is the preferred option for treatment for a great number of
      patients, SAs must be added to the treatment regimen of the majority of such
      patients. The costs associated with this treatment are greater than the cost of
      treatment with SAs alone.

PMID- 22397308
TI  - Chasing changing nanoparticles with time-resolved pair distribution function
      methods.
AB  - When materials are reduced to the nanoscale, their structure and reactivity can
      deviate greatly from the bulk or extended surface case. Using the archetypal
      example of supported Pt nanoparticles (ca. 2 nm diameter, 1 wt % Pt on Al(2)O(3))
      catalyzing CO oxidation to CO(2) during cyclic redox operation, we show that high
      energy X-ray total scattering, used with subsecond time resolution, can yield
      detailed, valuable insights into the dynamic behavior of nanoscale systems. This
      approach reveals how these nanoparticles respond to their environment and the
      nature of active sites being formed and consumed within the catalytic process.
      Specific insight is gained into the structure of the highly active Pt surface
      oxide that formed on the nanoparticles during catalysis.

PMID- 22397309
TI  - An evaluation of communication apprehension in adolescents with velopharyngeal
      inadequacy.
AB  - OBJECTIVE: This investigation evaluated the construct of communication
      apprehension (CA) in adolescents with velopharyngeal inadequacy (VPI). DESIGN:
      Prospective comparative study. SETTINGS: The investigation was conducted in a
      hospital-based clinic, voice laboratory, and the homes of participants.
      PARTICIPANTS: Two groups of children participated in this study. The first group
      was composed of 14 children between the ages of 8 and 14 years who attended the
      velopharyngeal inadequacy (VPI) clinic at our institution, and the second group
      was composed of 14 age-matched children from the community with no history of
      speech or voice disorders. INTERVENTIONS: The study involved completion of the
      Measure of Elementary Communication Apprehension (MECA) by all 28 participants
      (14 experimental and 14 control subjects). Reliability of the subjects' responses
      to the MECA was also evaluated. OUTCOME MEASURES: Communication apprehension
      scores obtained from the MECA were the main focus of the study. RESULTS: Children
      with VPI experienced significantly higher levels of CA than did those in the
      control group. Moderate-to-good reliability of the MECA was found. CONCLUSIONS:
      Based on these data, children with VPI may be experiencing increased levels of
      CA. Consequently, the experience of high CA has the potential to affect the
      communication performance and social functioning of children with VPI.

PMID- 22397310
TI  - Enantioresolution of 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl oxide using
      inclusion complex with chiral 2,2'-dihydroxy-1,1'-binaphtyl.
AB  - An enantioresolution of 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl oxide
      (BINAPO) into its enantiomers was achieved using the inclusion complex with a
      commerciallyavailable chiral 2,2'-dihydroxy-1,1'-binaphthyl ((R)-BINOL), giving
      the two enantiomers with 99% ee and 72% ee, respectively.

PMID- 22397311
TI  - Stable isotopes determination in some Romanian wines.
AB  - This paper presents a study concerning the isotopic fingerprint ((18)O and (13)C)
      of some wines prepared from relevant Romanian grape varieties (e.g. Feteasca Alba
      (FA), Feteasca Regala (FR) and Cabernet Sauvignon (CS)) obtained in different
      vintage years (2002, 2003, 2004, 2007 and 2008). These wines were obtained from
      different vineyards having a significant role in the wine market: Cotesti,
      Tohani, Stefanesti, Aiud, Cotnari, Bucium, Murfatlar, Bujoru, Dragasani and Valea
      Calugareasca. Several observations related to the dependence of isotope ratios on
      geographical origin and climatic conditions were drawn. The authentic wines
      obtained from the FA grape variety from six different vineyards showed delta(18)O
      values in the range of+3.28 (Cotesti region - 45  degrees 38'N/27  degrees 04'E)
      to-2.60 0/00 (Aiud region - 46  degrees 19'N/23  degrees 45'E). The delta(13)C
      values were very similar for all the samples with an average of about-26 0/00.
      The difference between the delta(18)O values was due to the different climatic
      zones, which have an influence on the delta(18)O values of wine water. For the
      wine variety CS obtained from the Dealu Mare-Tohani vineyard, production years
      2003 and 2004, a greater difference in the delta(18)O values of wine water
      ranging from 1.89 (in 2004) to 5.35 0/00 (in 2003) was noted. This difference is
      explained by the different mean annual temperatures in 2003 and 2004.

PMID- 22397312
TI  - Adverse effects of topical anesthetics for dermatologic procedures.
AB  - INTRODUCTION: Topical anesthetics are frequently used to decrease the pain
      associated with a variety of procedures including cutaneous surgery, cosmetic
      treatments and laser surgery. They are also routinely used in children prior to
      invasive procedures, such as venipuncture. The ideal topical anesthetic should
      safely increase patient comfort associated with these procedures with minimal
      potential for adverse effects. AREAS COVERED: Topical anesthetic formulations
      have evolved over the past several decades to include formulations with improved
      efficacy and side effect profiles. However, significant adverse events are still
      possible. EXPERT OPINION: Medical practitioners can mitigate the risk of side
      effects and toxicity with careful selection of anesthetic type, concentration,
      body location and dermatologic procedure. Compounded formulations should be used
      with caution in medical settings only on limited body surface areas without
      occlusion. This review presents a detailed analysis of products available,
      reported complications and an outline for appropriate use of topical anesthetics
      in combination with dermatologic procedures.

PMID- 22397314
TI  - Role of nuclear factor-kappaB regulators TNFAIP3 and CARD11 in Middle Eastern
      diffuse large B-cell lymphoma.
AB  - Aberrant nuclear factor-kappaB (NF-kappaB) regulation has been observed in many
      hematopoietic malignancies including diffuse large B-cell lymphoma (DLBCL).
      Considering the potential therapeutic utility of targeting NF-kappaB and its key
      modulators, we studied genetic alterations (mutations and amplifications) in
      TNFAIP3 and CARD11 genes in DLBCL samples. The incidence of CARD11 and TNFAIP3
      mutations was 10.7% and 4.6%, respectively. Interestingly, CARD11 amplification
      was seen in a significant proportion of cases of DLBCL (23%) and was linked to NF
      kappaB activation (p = 0.0142). Immunohistochemical analysis of DLBCL samples
      showed CARD11 overexpression and loss of TNFAIP3 in 17.7% (32/181) and 13.5%
      (24/178), respectively. Poor overall survival was noted in DLBCL harboring CARD11
      gene amplification (p = 0.0491). Our study reports the incidence of TNFAIP3 and
      CARD11 alterations in Saudi DLBCL, a potentially unique ethnic group, and
      highlights for the first time the role of CARD11 gene amplification as a novel
      mechanism for NF-kappaB activation in Middle Eastern DLBCL.

PMID- 22397313
TI  - Prolonged immunochemotherapy with rituximab, cytarabine and fludarabine added to
      cyclophosphamide, doxorubicin, vincristine and prednisolone and followed by
      rituximab maintenance in untreated elderly patients with mantle cell lymphoma: a
      prospective study by the Finnish Lymphoma Group.
AB  - There is no consensus on treatment strategies for elderly patients with mantle
      cell lymphoma (MCL). In this prospective phase II study we investigated whether
      the poor outcome could be improved, with reasonable toxicity, by prolonging the
      immunochemotherapy. Ten cycles of alternating cyclophosphamide, doxorubicin,
      vincristine and prednisolone (CHOP)/cytarabine (AraC) with eight doses of
      rituximab (R) were given as induction. The potential synergism of intermediate
      dose AraC and fludarabine was tested in cycles 6-8. Induction was followed by
      bimonthly rituximab maintenance for 2 years. The median age of the 60 included
      patients was 74 years, and the Mantle Cell Lymphoma International Prognostic
      Index (MIPI) was intermediate or high risk in 98% of the patients. The overall
      response rate was 95% (complete response/complete response unconfirmed 87%). The
      response of 11 patients improved with cycles 6-8 (R-fludarabine-AraC).
      Progression-free survival was 70% and overall survival 72% at 4 years,
      respectively. Treatment related mortality was 2%. Severe infections were rare,
      with only one grade 4 infection. More dose reductions were needed during
      fludarabine-containing courses as compared to R-AraC. In 20 patients a transient
      grade 4 neutropenia without severe infections was recorded during maintenance. In
      conclusion, elderly patients with MCL can be treated relatively intensively with
      acceptable toxicity.

PMID- 22397315
TI  - Reversible posterior leukoencephalopathy syndrome of bilateral thalamus in acute
      lymphoblastic leukemia.

PMID- 22397316
TI  - Fasudil improves survival and promotes skeletal muscle development in a mouse
      model of spinal muscular atrophy.
AB  - BACKGROUND: Spinal muscular atrophy (SMA) is the leading genetic cause of infant
      death. It is caused by mutations/deletions of the survival motor neuron 1 (SMN1)
      gene and is typified by the loss of spinal cord motor neurons, muscular atrophy,
      and in severe cases, death. The SMN protein is ubiquitously expressed and various
      cellular- and tissue-specific functions have been investigated to explain the
      specific motor neuron loss in SMA. We have previously shown that the RhoA/Rho
      kinase (ROCK) pathway is misregulated in cellular and animal SMA models, and that
      inhibition of ROCK with the chemical Y-27632 significantly increased the lifespan
      of a mouse model of SMA. In the present study, we evaluated the therapeutic
      potential of the clinically approved ROCK inhibitor fasudil. METHODS: Fasudil was
      administered by oral gavage from post-natal day 3 to 21 at a concentration of 30
      mg/kg twice daily. The effects of fasudil on lifespan and SMA pathological
      hallmarks of the SMA mice were assessed and compared to vehicle-treated mice. For
      the Kaplan-Meier survival analysis, the log-rank test was used and survival
      curves were considered significantly different at P < 0.05. For the remaining
      analyses, the Student's two-tail t test for paired variables and one-way analysis
      of variance (ANOVA) were used to test for differences between samples and data
      were considered significantly different at P < 0.05. RESULTS: Fasudil
      significantly improves survival of SMA mice. This dramatic phenotypic improvement
      is not mediated by an up-regulation of Smn protein or via preservation of motor
      neurons. However, fasudil administration results in a significant increase in
      muscle fiber and postsynaptic endplate size, and restores normal expression of
      markers of skeletal muscle development, suggesting that the beneficial effects of
      fasudil could be muscle-specific. CONCLUSIONS: Our work underscores the
      importance of muscle as a therapeutic target in SMA and highlights the beneficial
      potential of ROCK inhibitors as a therapeutic strategy for SMA and for other
      degenerative diseases characterized by muscular atrophy and postsynaptic
      immaturity.

PMID- 22397317
TI  - Oxidation of human growth hormone by oxygen-centered radicals: formation of Leu
      101 hydroperoxide and Tyr-103 oxidation products.
AB  - Human growth hormone (hGH) was exposed to oxygen-centered radicals generated
      through the thermolysis of AAPH in the presence of dioxygen. Such conditions
      mimic oxidative processes which protein pharmaceuticals can encounter during
      formulation in the presence of polysorbates. We detected the oxidation of Met to
      Met sulfoxide, the formation of protein carbonyls, the oxidation of Tyr to
      dityrosine and several additional Tyr oxidation products, the conformation
      dependent oxidation of Trp, and the site-specific formation of protein
      hydroperoxides. The sensitivity of Met oxidation correlates with their solvent
      accessible surface, i.e. the yields of MetSO decreased in the order Met-14 > Met
      125 > Met-170. Trp oxidation in native hGH was negligible, but was enhanced
      through denaturation. Dityrosine formed predominantly intramolecularly but did
      not contribute significantly to protein cross-linking. Hydroperoxides formed
      selectively on Leu-101 and were generated specifically by alkoxyl radicals,
      generated through the decomposition of peroxyl radicals. Tyr-103 was converted
      into a series of oxidation products characterized by mass shifts of Tyr + 14 Da
      and Tyr + 16 Da.

PMID- 22397319
TI  - Dose-response and threshold analysis of tumor prevalence after intratracheal
      instillation of six types of low- and high-surface-area particles in a chronic
      rat experiment.
AB  - Over a period of 20 years, rat experiments have consistently shown tumorigenic
      responses after exposure to poorly soluble low-toxicity particles (PSP). We
      performed a rigorous dose threshold analysis of a large previous rat study. Seven
      hundred and nine rats were intratracheally exposed to five different PSP: carbon
      black and titanium dioxide of low and high surface area, diesel emission
      particles (low surface area), and one soluble dust (amorphous silica, high
      surface area), at varying instilled total mass doses ranging from 3.0 mg to 120
      mg. A multivariable Cox model was applied to analyse lung tumor prevalence. The
      model was extended by a dose threshold or a dose saturation parameter. This
      statistical approach, which is new in animal studies, showed no better fit when
      using surface area or volume as dose metrics but found significantly higher tumor
      prevalence in animals instilled with high-surface-area dust particles.
      Interestingly, a dose threshold of about 10 mg mass dose (0.95 CI: 5 mg to 15 mg)
      emerged from our calculations. In addition, our statistical analysis demonstrated
      that tumor prevalence is saturated beyond 20 mg mass dose. In summary, our
      analyses showed that these data are compatible with earlier observations that
      high-surface-area particles induce more lung tumors and support the concept of a
      dose threshold for lung tumor after PSP exposures in the rat. However,
      collinearities in the data (particle type and dose were correlated by design) and
      the saturation phenomenon (506 out of 709 rats were exposed above the estimated
      saturation dose) limit generalization of these findings.

PMID- 22397318
TI  - Meningeal and cortical grey matter pathology in multiple sclerosis.
AB  - Although historically considered a disease primarily affecting the white matter
      of the central nervous system, recent pathological and imaging studies have
      established that cortical demyelination is common in multiple sclerosis and more
      extensive than previously appreciated. Subpial, intracortical and leukocortical
      lesions are the three cortical lesion types described in the cerebral and
      cerebellar cortices of patients with multiple sclerosis. Cortical demyelination
      may be the pathological substrate of progression, and an important pathologic
      correlate of irreversible disability, epilepsy and cognitive impairment. Cortical
      lesions of chronic progressive multiple sclerosis patients are characterized by a
      dominant effector cell population of microglia, by the absence of macrophagic and
      leukocytic inflammatory infiltrates, and may be driven in part by organized
      meningeal inflammatory infiltrates. Cortical demyelination is also present and
      common in early MS, is topographically associated with prominent meningeal
      inflammation and may even precede the appearance of classic white matter plaques
      in some MS patients. However, the pathology of early cortical lesions is
      different than that of chronic MS in the sense that early cortical lesions are
      highly inflammatory, suggesting that neurodegeneration in MS occurs on an
      inflammatory background and raising interesting questions regarding the role of
      cortical demyelination and meningeal inflammation in initiating and perpetuating
      the disease process in early MS.

PMID- 22397320
TI  - Transcriptomic and histopathology changes in rat lung after intratracheal
      instillation of polymers.
AB  - The lung toxicity of inhalable polymer materials is normally carried out by
      evaluation of the histopathology responses of rat lungs to repeat, nose-only,
      exposures of an inhalable aerosol of material in a 13-wk subchronic repeat dose
      toxicity study. The introduction of transcriptomics into toxicology has allowed
      the comparison of histopathological responses in target organs, after exposure,
      with the "signature" of gene expression ( Waters et al., 2003 ), characteristic
      of the pathology processes known to be involved in the response to inhaled
      particulates. The transcriptomic and histopathological changes have been examined
      in a dose response study of the rat lung to intratracheally administered acrylate
      polymer solutions at time points equivalent to those used in a 13-wk inhalation
      study with an additional 13-wk recovery period. The doses administered in the
      intratracheal study were equivalent to the total doses achieved in a comparable
      13-wk inhalation study. The changes in gene expression were found to be dose
      dependent, as was the histopathology. The changes in regulation of the genes
      expressed were also consistent with the histopathological responses, such as
      acute and chronic inflammation, commonly observed with inhalation exposure of the
      rat lungs to polymers. Functional classification of the genes affected highlight
      changes in inflammatory and immune response combined with macrophage recruitment,
      as well as cell adhesion and matrix formation. This would suggest a degree of
      tissue remodeling and is consistent with the histopathology observed. With
      further confirmation of the consistency of this response, the use of a
      transcriptomic approach in toxicology may be valuable in defining "signature"
      markers for the acute and chronic inflammation induced by polymers, or other
      inhalables, deposited in the lung. Osteopontin, in particular, a gene implicated
      in granuloma formation during chronic tissue damage, was significantly
      upregulated at high levels of exposure to polymer.

PMID- 22397321
TI  - Chronic exposure to urban air pollution induces structural alterations in murine
      pulmonary and coronary arteries.
AB  - Epidemiological studies have shown that air pollution increases cardiovascular
      morbidity and mortality. Objective markers of cardiovascular risk have also been
      associated with increases in ambient pollution. This study was designed to assess
      whether prolonged exposure to ambient levels of air pollution may induce
      structural alterations of pulmonary and cardiac vessels. Mice were chronically
      exposed to ambient levels of air pollution in downtown Sao Paulo, Brazil. The
      animals were maintained in exposure chambers, 24 h/day, 7 days/wk, during 4 mo.
      One group was exposed to ambient air, and the control group was exposed to
      filtered air. Morphometric measurements of the ratio between the lumen and wall
      (L/W) areas were performed on transverse sections of renal, pulmonary, and
      coronary arteries. As expected, lumen/wall ratios increased with arterial caliber
      (p < .001). A significant decrease of L/W with exposure to air pollution was
      detected in pulmonary (p = .03) and coronary (p = .021) arteries, whereas no
      effects of air pollution were observed in renal vessels. Our results indicate
      that animals chronically exposed to ambient air pollution develop a significant
      thickening of the arterial wall in the coronary and pulmonary circulation.

PMID- 22397322
TI  - The retention of tobacco smoke constituents in the human respiratory tract.
AB  - Measurements on the retention of cigarette smoke constituents in the human
      respiratory tract have been undertake for more than 100 years. The first studies
      on nicotine retention were begun by Lehmann in Germany in 1903 and published in
      1908. The first studies on the retention of smoke particulate matter were
      published by Baumbereger in the United States in 1923. Since those early
      publications, many studies have been undertaken, more or less continuously. This
      article is a review of the work that has been done over the last 100 years,
      including a large number of unpublished studies undertaken by British American
      Tobacco in Southampton, UK. The techniques used have evolved over the years and
      there is a certain amount of variation in the data. However, the general trends
      in the results are reassuringly consistent. The bulk of the studies indicate
      that, on average, 60 to 80% of the mainstream smoke particulate matter is
      retained in the lungs after inhalation. For nicotine, carbon monoxide, nitric
      oxide, and aldehydes the total retentions are of the order of 90-100, 55-65, 100,
      and approximately 90%, respectively, during cigarette smoke inhalation. For most
      smoke constituents the retentions in the mouth only are considerably smaller than
      in the whole respiratory tract. The lung retention values for smoke particulate
      matter are dependent on the depth of inhalation, hold time in the lungs,
      exhalation volume, and other factors. However, the degree of nicotine retention
      following inhalation is not markedly influenced by changes in respiratory
      parameters. Furthermore, the percentage retentions for smoke particulate matter
      and nicotine are smaller for nonsmoking subjects exposed to environmental tobacco
      smoke than with active smoking. The smoke retentions are related to properties of
      the smoke aerosol particles and gases and their behavior as they travel through
      the respiratory tract. This includes particle growth in the respiratory tract and
      evaporation of gases out of the particles, and relevant aspects of these
      processes are also reviewed.

PMID- 22397323
TI  - Toxicological interactions in the respiratory system after inhalation of ozone
      and sulfuric acid aerosol mixtures.
AB  - A factorial design study was performed to examine the acute effects of inhaled
      acid particles alone and in mixtures with ozone to test the hypothesis that acid
      particles and ozone would act synergistically. Sprague-Dawley rats were exposed
      nose-only for a single 4-h period to all 9 possible combinations of purified air
      and 2 concentrations each of O(3) (0.3 and 0.6 ppm) and submicrometer (0.3 MUm
      mass median diameter [MMD]) sulfuric acid aerosols H(2)SO(4) (0.5 and 1.0
      mg/m(3)). Respiratory-tract injury and impairment of alveolar macrophage
      functions were evaluated. Two-way analyses of variance were used to test for
      significance of main effects and statistical interactions, and Tukey multiple
      comparison tests were used to test the significance of differences between group
      mean values. Addition of H(2)SO(4) to O(3)-containing atmospheres resulted in
      significant H(2)SO(4) concentration-dependent reductions in O(3)-induced
      inflammatory responses, and H(2)SO(4), alone and in combination with O(3),
      depressed some functions of innate immunity. DNA synthesis in nasal, tracheal,
      and lung tissue following pollutant exposure, which is an index of injury or
      killing of epithelial cells, was significantly increased by O(3) but not by
      H(2)SO(4) when administered alone, compared to purified air. When administered
      with O(3), H(2)SO(4) did not reduce the effects of O(3) on DNA synthesis in the
      trachea or the lung, but did reduce the DNA synthesis response to O(3) in the
      nose. No significant changes in antibody-directed Fc receptor (FcR) binding of
      sheep red blood cells by alveolar macrophages were observed, but macrophage
      phagocytic activity was significantly reduced by the pollutant exposures. In
      summary, the results of this study indicate significant interactions between O(3)
      and H(2)SO(4) in concurrent exposures; however, the findings do not support the
      hypothesis that O(3) and H(2)SO(4) act synergistically in rats after single 4-h
      exposures.

PMID- 22397324
TI  - Respiration in Sprague-Dawley rats during pregnancy.
AB  - Minute ventilation and tidal volume increase in humans during pregnancy. Little
      data exists, however, on the respiration in pregnant rats, despite their
      widespread use as an animal model. Since respiration will affect the
      pharmacokinetics of volatile compounds and ultimately the dose to the fetus, we
      conducted a study to evaluate respiration in rats during pregnancy. Whole-body
      plethysmography was used to measure the breathing frequency and tidal volume
      approximately every other day from gestation day (GD) 1 to 21 in 16 timed
      pregnant and 16 nonpregnant, female, Sprague-Dawley rats. Minute ventilation was
      calculated as a product of the breathing frequency and tidal volume, and the body
      weight of each rat was used to determine the scaled ventilation. Multivariate
      analysis of variance methods for a repeated-measures design were used to analyze
      the respiratory data. Breathing frequency was not affected by pregnancy; however,
      tidal volume was somewhat greater in pregnant versus nonpregnant rats. The
      increase in tidal volume resulted in significantly increased minute ventilation
      in pregnant rats compared to nonpregnant rats during the latter period of
      gestation. Due to the increased body weight of the pregnant rats, the scaled
      ventilation at the end of gestation was significantly lower in pregnant rats
      compared to nonpregnant rats. This study provides important reference values that
      can be used in pharmacokinetic models during pregnancy.

PMID- 22397325
TI  - Contact high: Mania proneness and positive perception of emotional touches.
AB  - How do extreme degrees of positive emotion-such as those characteristic of mania
      influence emotion perception? The present study investigated how mania proneness,
      assessed using the Hypomanic Personality Scale, influences the perception of
      emotion via touch. Using a validated dyadic interaction paradigm for
      communicating emotion through touch (Hertenstein, Keltner, App, Bulleit, &
      Jaskolka, 2006), participants (N=53) received eight different touches to their
      forearm from a stranger and then identified the emotion via forced-choice
      methodology. Mania proneness predicted increased overall accuracy in touch
      perception, particularly for positive emotion touches, as well as the over
      attribution of positive and under-attribution of negative emotions across all
      touches. These findings highlight the effects of positive emotion extremes on the
      perception of emotion in social interactions.

PMID- 22397326
TI  - Assessment of providers' referral decisions in rural Burkina Faso: a
      retrospective analysis of medical records.
AB  - BACKGROUND: A well-functioning referral system is fundamental to primary health
      care delivery. Understanding the providers' referral decision-making process
      becomes critical. This study's aim was to assess the correctness of diagnoses and
      appropriateness of the providers' referral decisions from health centers (HCs) to
      district hospitals (DHs) among patients with severe malaria and pneumonia.
      METHODS: A record review of twelve months of consultations was conducted covering
      eight randomly selected HCs to identify severe malaria (SM) cases among children
      under five and pneumonia cases among adults. The correctness of the diagnosis and
      appropriateness of providers' referral decisions were determined using the
      National Clinical Guidebook as a 'gold standard'. RESULTS: Among the 457 SM cases
      affecting children under five, only 66 cases (14.4%) were correctly diagnosed and
      of those 66 correctly diagnosed cases, 40 cases (60.6%) received an appropriate
      referral decision from their providers. Within these 66 correctly diagnosed SM
      cases, only 60.6% were appropriately referred. Among the adult pneumonia cases,
      5.9% (79/1331) of the diagnoses were correctly diagnosed; however, the
      appropriateness rate of the provider's referral decision was 98.7% (78/79). There
      was only one case that should not have been referred but was referred.
      CONCLUSIONS: The adherence to the National Guidelines among the health center
      providers when making a diagnosis was low for both severe malaria cases and
      pneumonia cases. The appropriateness of the referral decisions was particularly
      poor for children with severe malaria. Health center providers need to be better
      trained in the diagnostic process and in disease management in order to improve
      the performance of the referral system in rural Burkina Faso.

PMID- 22397327
TI  - Riedel's thyroiditis - a case report with genes' expression studies.
AB  - BACKGROUND: Genetic background of Riedel's thyroiditis remains unknown. Herein,
      we describe our results of studies on genes expression levels in Riedel's
      thyroiditis. CASE REPORT AND GENETIC FINDINGS: We report the case of 48-year old
      woman with Riedel's thyroiditis who has presented unusual course of disease with
      non-specific cervical discomfort, though as with no pain and/or no compression
      symptoms. After surgery, thyroid specimens were quantitatively evaluated,
      regarding PIK3CA, PIK3CD, PIK3CG, Tg, TGFB1, THRB, COL1, CDKN1C, CDH3 and
      CACNA2D2 genes expression levels, by real-time PCR in the ABI PRISM(r) 7500
      Sequence Detection System. Out of 10 above genes, in 2 cases the expression was
      higher than in respective Controls of unchanged thyroid tissue. In the remaining
      8 cases, expression in question became comparable or lower as in Controls.
      DISCUSSION: The association between increased expression levels of PIK3CA and
      CDH3 genes and Riedel's thyroiditis is not well-defined. However, the increased
      expression of PIK3CA and CDH3 genes in our case report and in previous studies of
      other authors on various malignancies may suggest possible molecular relation
      between Riedel's thyroiditis and certain neoplastic processes, the relation of
      which requires further genetic evaluation. It is to be stressed that gene
      expression studies in Riedel's thyroiditis are difficult to perform, mainly due
      to fibrosis, resulting in scarce thyroid specimens and - in consequence - small
      amount of genetic material.

PMID- 22397328
TI  - The use of proteomics for systematic analysis of normal and transformed
      hematopoietic stem cells.
AB  - Blood cell production involves the commitment and differentiation of
      hematopoietic stem cells to committed progenitor cells which undergo a programmed
      development to form mature cells such as neutrophils, macrophages and
      lymphocytes. This complex process can be disrupted in diseases such as the
      leukemias and myeloproliferative disorders by oncogenes such as protein tyrosine
      kinases. The analysis of expression patterns for specific genes suggests that the
      regulation of protein expression can be achieved in a posttranslational fashion.
      Post-translational protein modification, such as phosphorylation and acetylation
      govern events in blood cell production and yet cannot be measured using
      conventional molecular biology approaches. For this reason a suite of techniques
      in mass spectrometry needs to be applied to define regulation and disregulation
      in normal and abnormal hematopoiesis. These approaches include discovery
      proteomics with relative quantification of thousands of proteins. Alternatively
      targeted examination of a single protein to identify its interaction partners or
      post-translational modifications using mass spectrometry reveals much mechanistic
      detail. The use of mass spectrometry and proteomics approaches in stem cell and
      leukemia studies has thus far revealed a good deal of information on
      hematopoiesis. Further application of the proteomics approach is a necessity to
      gain true insight into regulatory processes governing the production of billions
      of blood cells a day, and ways in which that process can be manipulated to
      therapeutic advantage.

PMID- 22397330
TI  - Modulation of cellular S1P levels with a novel, potent and specific inhibitor of
      sphingosine kinase-1.
AB  - SphK (sphingosine kinase) is the major source of the bioactive lipid and GPCR (G
      protein-coupled receptor) agonist S1P (sphingosine 1-phosphate). S1P promotes
      cell growth, survival and migration, and is a key regulator of lymphocyte
      trafficking. Inhibition of S1P signalling has been proposed as a strategy for
      treatment of inflammatory diseases and cancer. In the present paper we describe
      the discovery and characterization of PF-543, a novel cell-permeant inhibitor of
      SphK1. PF-543 inhibits SphK1 with a K(i) of 3.6 nM, is sphingosine-competitive
      and is more than 100-fold selective for SphK1 over the SphK2 isoform. In 1483
      head and neck carcinoma cells, which are characterized by high levels of SphK1
      expression and an unusually high rate of S1P production, PF-543 decreased the
      level of endogenous S1P 10-fold with a proportional increase in the level of
      sphingosine. In contrast with past reports that show that the growth of many
      cancer cell lines is SphK1-dependent, specific inhibition of SphK1 had no effect
      on the proliferation and survival of 1483 cells, despite a dramatic change in the
      cellular S1P/sphingosine ratio. PF-543 was effective as a potent inhibitor of S1P
      formation in whole blood, indicating that the SphK1 isoform of sphingosine kinase
      is the major source of S1P in human blood. PF-543 is the most potent inhibitor of
      SphK1 described to date and it will be useful for dissecting specific roles of
      SphK1-driven S1P signalling.

PMID- 22397331
TI  - The multisite translational community trial and community-based participatory
      research: a failure to communicate?

PMID- 22397334
TI  - The tobacco innuendo.

PMID- 22397329
TI  - Tranexamic acid: a review of its use in the treatment of hyperfibrinolysis.
AB  - Tranexamic acid, a synthetic derivative of the amino acid lysine, is an
      antifibrinolytic agent that acts by binding to plasminogen and blocking the
      interaction of plasmin(ogen) with fibrin, thereby preventing dissolution of the
      fibrin clot. Tranexamic acid (Transamin(r)) is indicated in Japan for use in
      certain conditions with abnormal bleeding or bleeding tendencies in which local
      or systemic hyperfibrinolysis is considered to be involved. This article reviews
      the efficacy and tolerability of tranexamic acid in conditions amenable to
      antifibrinolytic therapy and briefly overviews the pharmacological properties of
      the drug. In large, randomized controlled trials, tranexamic acid generally
      significantly reduced perioperative blood loss compared with placebo in a variety
      of surgical procedures, including cardiac surgery with or without cardiopulmonary
      bypass, total hip and knee replacement and prostatectomy. In many instances,
      tranexamic acid also reduced transfusion requirements associated with surgery. It
      also reduced blood loss in gynaecological bleeding disorders, such as heavy
      menstrual bleeding, postpartum haemorrhage and bleeding irregularities caused by
      contraceptive implants. Tranexamic acid significantly reduced all-cause mortality
      and death due to bleeding in trauma patients with significant bleeding,
      particularly when administered early after injury. It was also effective in
      traumatic hyphaema, gastrointestinal bleeding and hereditary angioneurotic
      oedema. While it reduces rebleeding in subarachnoid haemorrhage, it may increase
      ischaemic complications. Pharmacoeconomic analyses predicted that tranexamic acid
      use in surgery and trauma would be very cost effective and potentially life
      saving. In direct comparisons with other marketed agents, tranexamic acid was at
      least as effective as epsilon-aminocaproic acid and more effective than
      desmopressin in surgical procedures. It was more effective than desmopressin,
      etamsylate, flurbiprofen, mefenamic acid and norethisterone, but less effective
      than the levonorgestrel-releasing intra-uterine device in heavy menstrual
      bleeding and was as effective as prednisolone in traumatic hyphaema. Tranexamic
      acid was generally well tolerated. Most adverse events in clinical trials were of
      mild or moderate severity; severe or serious events were rare. Therefore, while
      high-quality published evidence is limited for some approved indications,
      tranexamic acid is an effective and well tolerated antifibrinolytic agent.

PMID- 22397336
TI  - We are the 99 percent.

PMID- 22397337
TI  - Social justice in pandemic preparedness.
AB  - Pandemic influenza planning in the United States violates the demands of social
      justice in 2 fundamental respects: it embraces the neutrality of procedural
      justice at the expense of more substantive concern with health disparities, thus
      perpetuating a predictable and preventable social injustice, and it fails to move
      beyond lament to practical planning for alleviating barriers to accessing care. A
      pragmatic social justice approach, addressing both health disparities and access
      barriers, should inform pandemic preparedness. Achieving social justice goals in
      pandemic response is challenging, but strategies are available to overcome the
      obstacles. The public engagement process of one state's pandemic ethics project
      influenced the development of these strategies.

PMID- 22397338
TI  - The expert and the lay public: reflections on influenza A (H1N1) and the risk
      society.
AB  - Trust between the lay public and scientific experts is a key element to ensuring
      the efficient implementation of emergency public health measures. In modern risk
      societies, the management and elimination of risk have become preeminent drivers
      of public policy. In this context, the protection of public trust is a complex
      task. Those actors involved in public health decision-making and implementation
      (e.g., mass vaccination for influenza A virus) are confronted with growing
      pressures and responsibility to act. However, they also need to accept the limits
      of their own expertise and recognize the ability of lay publics to understand and
      be responsible for public health. Such a shared responsibility for risk
      management, if grounded in participative public debates, can arguably strengthen
      public trust in public health authorities and interventions.

PMID- 22397339
TI  - Benefits and effectiveness of administering pneumococcal polysaccharide vaccine
      with seasonal influenza vaccine: an approach for policymakers.
AB  - For the influenza pandemic of 2009-2010, countries responded to the direct threat
      of influenza but may have missed opportunities and strategies to limit secondary
      pneumococcal infections. Delivering both vaccines together can potentially
      increase pneumococcal polysaccharide vaccine (PPV23) immunization rates and
      prevent additional hospitalizations and mortality in the elderly and other high
      risk groups. We used PubMed to review the literature on the concomitant use of
      PPV23 with seasonal influenza vaccines. Eight of 9 clinical studies found that a
      concomitant program conferred clinical benefits. The 2 studies that compared the
      cost-effectiveness of different strategies found concomitant immunization to be
      more cost-effective than either vaccine given alone. Policymakers should consider
      a stepwise strategy to reduce the burden of secondary pneumococcal infections
      during seasonal and pandemic influenza outbreaks.

PMID- 22397340
TI  - A dangerous curve: the role of history in America's scoliosis screening programs.
AB  - In 2004, the US Preventive Services Task Force called for an end to scoliosis
      screening in US public schools. However, screening endures, although most nations
      have ended their screening programs. Why? Explanations range from America's
      unique fee-for-service health care system and its encouragement of high-cost
      medical specialism to the nation's captivation with new surgeries and
      technologies. I highlight another, more historical, reason: the persistence of
      the belief that spinal curvature is a sign of a progressive disease or
      disability. Despite improved health and the mid-20th-century discovery of
      antibiotics and vaccines that all but eradicated the diseases historically
      associated with scoliosis (e.g., polio and tuberculosis), the health fears
      associated with spinal curvature never fully dissipated. Scoliosis is still seen
      as a "dangerous curve," although the exact nature of the health risk remains
      unclear.

PMID- 22397341
TI  - A model to translate evidence-based interventions into community practice.
AB  - There is a tension between 2 alternative approaches to implementing community
      based interventions. The evidence-based public health movement emphasizes the
      scientific basis of prevention by disseminating rigorously evaluated
      interventions from academic and governmental agencies to local communities.
      Models used by local health departments to incorporate community input into their
      planning, such as the community health improvement process (CHIP), emphasize
      community leadership in identifying health problems and developing and
      implementing health improvement strategies. Each approach has limitations.
      Modifying CHIP to formally include consideration of evidence-based interventions
      in both the planning and evaluation phases leads to an evidence-driven community
      health improvement process that can serve as a useful framework for uniting the
      different approaches while emphasizing community ownership, priorities, and
      wisdom.

PMID- 22397342
TI  - Rapid HIV testing in dental practices.
AB  - Despite increasing discussion about the dental care setting as a logical,
      potentially fruitful venue for rapid HIV testing, dentists' willingness to take
      on this task is unclear. Semistructured interviews with 40 private practice
      dentists revealed their principal concerns regarding offering patients HIV
      testing were false results, offending patients, viewing HIV testing as outside
      the scope of licensure, anticipating low patient acceptance of HIV testing in a
      dental setting, expecting inadequate reimbursement, and potential negative impact
      on the practice. Dentists were typically not concerned about transmission risks,
      staff opposition to testing, or making referrals for follow-up after a positive
      result. A larger cultural change may be required to engage dentists more actively
      in primary prevention and population-based HIV screening.

PMID- 22397343
TI  - The common ground preparedness framework: a comprehensive description of public
      health emergency preparedness.
AB  - Currently, public health emergency preparedness (PHEP) is not well defined.
      Discussions about public health preparedness often make little progress, for lack
      of a shared understanding of the topic. We present a concise yet comprehensive
      framework describing PHEP activities. The framework, which was refined for 3
      years by state and local health departments, uses terms easily recognized by the
      public health workforce within an information flow consistent with the National
      Incident Management System. To assess the framework's completeness, strengths,
      and weaknesses, we compare it to 4 other frameworks: the RAND Corporation's
      PREPARE Pandemic Influenza Quality Improvement Toolkit, the National Response
      Framework's Public Health and Medical Services Functional Areas, the National
      Health Security Strategy Capabilities List, and the Centers for Disease Control
      and Prevention's PHEP Capabilities.

PMID- 22397344
TI  - Maternal perceptions of help from home visits by nurse-community health worker
      teams.
AB  - We used data from a home visiting trial to examine low-income women's perceptions
      of services received from nurses (the community care [CC] group) and from a nurse
      community health worker (CHW) team. More mothers in the nurse-CHW group than in
      the CC group reported receiving help in all of the categories assessed. For both
      groups, assistance with health education ranked highest among the types of
      assistance received. A higher percentage of women in the nurse-CHW group than the
      CC group reported that they received psychosocial help.

PMID- 22397345
TI  - The role of health systems and policies in promoting safe delivery in low- and
      middle-income countries: a multilevel analysis.
AB  - We aimed to measure the contribution of national factors, particularly health
      system characteristics, to the individual likelihood of professionally attended
      delivery ("safe delivery") for women in low- and middle-income countries. Using
      Demographic and Health Survey data for 165,774 women in 31 countries, we
      estimated multilevel logistic regression models to measure the contribution of
      national economic and health system characteristics to likelihood of attended
      delivery. More health workers, higher national income, urbanization, and lower
      income inequality were associated with higher odds of attended delivery.
      Macrosocial factors increase utilization of attended delivery and may be more
      efficient in reducing maternal mortality than are interventions aimed at
      individual women.

PMID- 22397346
TI  - Worrying about terrorism and other acute environmental health hazard events.
AB  - OBJECTIVES: To better understand why some people worry more about terrorism
      compared with others, we measured how much US residents worried about a terrorist
      event in their area and examined the association of their fears with their
      concerns about acute and chronic hazards and other correlates. METHODS: In 2008
      (n = 600) and 2010 (n = 651), we performed a random-digit dialing national
      landline telephone survey. We asked about worries about terrorism and 5 other
      environmental health hazard issues. We also collected demographic and
      socioeconomic data. RESULTS: Only 15% worried "a great deal" about a terrorist
      event in their area and 18% to 33% were greatly concerned about other
      environmental issues. Fear about acute hazard events was a stronger predictor of
      a great deal of concern about terrorism than were age, race/ethnicity, gender,
      educational achievement, and other correlates. CONCLUSIONS: Those who worried
      most about acute environmental health hazard events were most likely to worry
      about terrorism. Also, those who were older, poorer, Blacks, or Latinos, or who
      lived in populous urban areas felt they were most vulnerable to terrorist
      attacks. We recommend methods to involve US citizens as part of disaster
      planning.

PMID- 22397347
TI  - Religious climate and health risk behaviors in sexual minority youths: a
      population-based study.
AB  - OBJECTIVES: We examined whether the health risk behaviors of lesbian, gay, and
      bisexual (LGB) youths are determined in part by the religious composition of the
      communities in which they live. METHODS: Data were collected from 31,852 high
      school students, including 1413 LGB students, who participated in the Oregon
      Healthy Teens survey in 2006 through 2008. Supportive religious climate was
      operationalized according to the proportion of individuals (of the total number
      of religious adherents) who adhere to a religion supporting homosexuality.
      Comprehensive data on religious climate were derived from 85 denominational
      groups in 34 Oregon counties. RESULTS: Among LGB youths, living in a county with
      a religious climate that was supportive of homosexuality was associated with
      significantly fewer alcohol abuse symptoms (odds ratio [OR] = 0.58; 95%
      confidence interval [CI] = 0.40, 0.85) and fewer sexual partners (OR = 0.77; 95%
      CI = 0.60, 0.99). The effect of religious climate on health behaviors was
      stronger among LGB than heterosexual youths. Results remained robust after
      adjustment for multiple confounding factors. CONCLUSIONS: The religious climate
      surrounding LGB youths may serve as a determinant of their health risk behaviors.

PMID- 22397348
TI  - US cultural involvement and its association with suicidal behavior among youths
      in the Dominican Republic.
AB  - OBJECTIVES: We examined how US cultural involvement related to suicide attempts
      among youths in the Dominican Republic. METHODS: We analyzed data from a
      nationally representative sample of youths attending high school in the Dominican
      Republic (n = 8446). The outcome of interest was a suicide attempt during the
      past year. The US cultural involvement indicators included time spent living in
      the United States, number of friends who had lived in the United States, English
      proficiency, and use of US electronic media and language. RESULTS: Time lived in
      the United States, US electronic media and language, and number of friends who
      had lived in the United States had robust positive relationships with suicide
      attempts among youths residing in the Dominican Republic. CONCLUSIONS: Our
      results are consistent with previous research that found increased risk for
      suicide or suicide attempts among Latino youths with greater US cultural
      involvement. Our study adds to this research by finding similar results in a
      nonimmigrant Latin American sample. Our results also indicate that suicide
      attempts are a major public health problem among youths in the Dominican
      Republic.

PMID- 22397349
TI  - Trends in risk perceptions and vaccination intentions: a longitudinal study of
      the first year of the H1N1 pandemic.
AB  - OBJECTIVES: We sought to evaluate longitudinal trends in people's risk
      perceptions and vaccination intentions during the 2009 H1N1 pandemic. METHODS: We
      used data from 10 waves of a US national survey focusing on the H1N1 pandemic
      (administered between May 2009 and January 2010) to conduct a longitudinal
      analysis of adult respondents' risk perceptions and vaccination intentions.
      RESULTS: Self-reported perceived risk of becoming infected with H1N1 paralleled
      H1N1 activity throughout the pandemic's first year. However, intention to be
      vaccinated declined from 50% (May 2009) to 16% (January 2010) among those who
      remained unvaccinated (27% had been vaccinated by January 2010). Respondents who
      indicated that they had previously been vaccinated against seasonal influenza
      reported significantly higher H1N1 vaccination intentions than those who had not
      been vaccinated (67% vs 26%; P < .001). CONCLUSIONS: Reported intention to be
      vaccinated declined well before vaccine became available and decreased throughout
      the pandemic year. To the extent that prior vaccination for seasonal influenza
      vaccination is a strong correlate of H1N1 risk perceptions, encouraging seasonal
      influenza vaccination may benefit pandemic preparedness efforts.

PMID- 22397350
TI  - The effects of smoking-related television advertising on smoking and intentions
      to quit among adults in the United States: 1999-2007.
AB  - OBJECTIVES: We investigated whether state-sponsored antitobacco advertisements
      are associated with reduced adult smoking, and interactions between smoking
      related advertising types. METHODS: We measured mean exposure to smoking-related
      advertisements with television ratings for the top-75 US media markets from 1999
      to 2007. We combined these data with individual-level Current Population Surveys
      Tobacco Use Supplement data and state tobacco control policy data. RESULTS:
      Higher exposure to state-sponsored, Legacy, and pharmaceutical advertisements was
      associated with less smoking; higher exposure to tobacco industry advertisements
      was associated with more smoking. Higher exposure to state- and Legacy-sponsored
      advertisements was positively associated with intentions to quit and having made
      a past-year quit attempt; higher exposure to ads for pharmaceutical cessation
      aids was negatively associated with having made a quit attempt. There was a
      significant negative interaction between state- and Legacy-sponsored
      advertisements. CONCLUSIONS: Exposure to state-sponsored advertisements was far
      below Centers for Disease Control and Prevention-recommended best practices. The
      significant negative relationships between antismoking advertising and adult
      smoking provide strong evidence that tobacco-control media campaigns help reduce
      adult smoking. The significant negative interaction between state- and Legacy
      sponsored advertising suggests that the campaigns reinforce one another.

PMID- 22397353
TI  - Public attitudes regarding banning of cigarettes and regulation of nicotine.
AB  - Knowledge of current public opinion is important as the Food and Drug
      Administration (FDA) applies the best scientific evidence available to tobacco
      product regulation. Based on a nationally representative survey of the US adult
      population, we report 43% support for banning of cigarettes, 65% for reducing
      nicotine, and 77% for reducing nicotine if such an action could cause fewer
      children to become addicted to cigarettes. The FDA should consider protecting
      children by removing all but non-addictive cigarettes from the marketplace.

PMID- 22397354
TI  - Exposure to natural cold and heat: hypothermia and hyperthermia Medicare claims,
      United States, 2004-2005.
AB  - OBJECTIVES: We measured the burden of hypothermia- and hyperthermia-related
      health care visits, identified risk factors, and determined the health care costs
      associated with environmental heat or cold exposure among Medicare beneficiaries.
      METHODS: We obtained Medicare fee-for-service claims data of inpatient and
      outpatient health care visits for hypothermia and hyperthermia from 2004 to 2005.
      We examined the distribution and differences of visits by age, sex, race,
      geographic regions, and direct costs. We estimated rate ratios to determine risk
      factors. RESULTS: Hyperthermia-related visits (n = 10,007) were more frequent
      than hypothermia-related visits (n = 8761) for both years. However, hypothermia
      related visits resulted in more deaths (359 vs 42), higher mortality rates (0.50
      per 100,000 vs 0.06 per 100,000), higher inpatient rates (5.29 per 100,000 vs
      1.76 per 100,000), longer hospital stays (median days = 4 vs 2), and higher total
      health care costs ($98 million vs $36 million). CONCLUSIONS: This study
      highlighted the magnitude of these preventable conditions among older adults and
      disabled persons and the burden on the Medicare system. These results can help
      target public education and preparedness activities for extreme weather events.

PMID- 22397356
TI  - Development and application of 15N-tracer substances for measuring the whole-body
      protein turnover rates in the human, especially in neonates: a review.
AB  - Our research group of the Children's Hospital of the University of Rostock
      (Rostock group) has long-time experience in (15)N-labelling and in using yeast
      protein and its hydrolysates for tracer kinetic studies to evaluate parameters of
      the whole-body protein metabolism in premature infants. The particular advantage
      of applying an economically convenient, highly (15)N-enriched, and completely
      labelled yeast protein for evaluating protein turnover rates is the fact that the
      (15)N dose is spread among all proteinogenic amino acids. The absorption has been
      improved by hydrolysing [(15)N]yeast protein with thermitase into a mixture of
      amino acids, dipeptides and tripeptides so that faecal analysis becomes
      unnecessary when determining turnover rates. The review shows that, in contrast
      to the application of single (15)N-labelled amino acids with resulting
      overestimation of protein turnover rates, the (15)N-labelled yeast protein
      thermitase hydrolysate represents the amino acid metabolism more closely without
      causing amino acid imbalances. The (15)N-labelled yeast protein thermitase
      hydrolysate leads to the estimation of reliable protein turnover rates,
      particularly in premature infants.

PMID- 22397357
TI  - Engineering liposomes of leaf extract of seabuckthorn (SBT) by supercritical
      carbon dioxide (SCCO2)-mediated process.
AB  - Seabuckthorn (SBT; Hipphophae rhamnoides) leaf extract obtained by supercritical
      carbon dioxide (SCCO(2)) using ethanol as an entrainer, containing mainly
      flavanoids as bioactive principles with antioxidant and antibacterial properties,
      was used for the preparation of liposomes. Liposomes are promising drug carriers
      with sustained release because they can enhance the membrane penetration of
      drugs, deliver the entrapped drugs across cell membranes, and improve extract
      stability and bioavailability. The aim of the present study was to compare the
      two different methods of liposome production: the Bangham thin-film method and
      SCCO(2) gas antisolvent method (SCCO(2) GAS) for the incorporation of SBT leaf
      extract in terms of particle size, morphology, encapsulation efficiency,
      antioxidant activity, and thermal stability. Liposomes obtained with the thin
      film method were multilamellar vesicles with average particle size (3,740 nm),
      encapsulation efficiency (14.60%), and particle-size range (1.57-6.0 um),
      respectively. On the other hand, liposomes by the SCCO(2) GAS method were
      nanosized (930 nm) with an improved encapsulation efficiency (28.42%) and narrow
      range of size distribution (0.48-1.07 um), respectively. Further, the antioxidant
      activity of leaf extract of SBT was determined by the 2 diphenyl-1-picrylhydrazyl
      method and expressed as Trolox equivalents as well as of the intercalated extract
      in liposomes. The oxidative stability of SBT encapsulated in liposomes was again
      estimated using differential scanning calorimetry (DSC). Thermal-oxidative
      decomposition of the samples (i.e., pure liposomes and encapsulated extracts) and
      the modification of the main transition temperature for the lipid mixture and the
      splitting of the calorimetric peak in the presence of the antioxidants were also
      studied by DSC. After encapsulation in liposomes, antioxidant activity proved to
      be higher than those of the same extracts in pure form.

PMID- 22397355
TI  - Genetic, physiological, and lifestyle predictors of mortality in the general
      population.
AB  - OBJECTIVES: We investigated the quality of 162 variables, focusing on the
      contribution of genetic markers, used solely or in combination with other
      characteristics, when predicting mortality. METHODS: In 5974 participants from
      the Rotterdam Study, followed for a median of 15.1 years, 7 groups of factors
      including age and gender, genetics, socioeconomics, lifestyle, physiological
      characteristics, prevalent diseases, and indicators of general health were
      related to all-cause mortality. Genetic variables were identified from 8 genome
      wide association scans (n = 19,033) and literature review. RESULTS: We observed
      3174 deaths during follow-up. The fully adjusted model (C-statistic for 15-year
      follow-up [C15y] = 0.80; 95% confidence interval [CI] = 0.79, 0.81) predicted
      mortality well [corrected]. Most of the additional information apart from age and
      sex stemmed from physiological markers, prevalent diseases, and general health.
      Socioeconomic factors and lifestyle contributed meaningfully to mortality risk
      prediction with longer prediction horizon. Although specific genetic factors were
      independently associated with mortality, jointly they contributed little to
      mortality prediction (C(15y) = 0.56; 95% CI = 0.55, 0.57). CONCLUSIONS: Mortality
      can be predicted reasonably well over a long period. Genetic factors
      independently predict mortality, but only modestly more than other risk
      indicators.

PMID- 22397358
TI  - Assessing whole body vibration exposure for use in epidemiological studies of
      back injuries: measurements, observations and self-reports.
AB  - Improved assessment of whole body vibration exposure is needed for
      epidemiological studies investigating the causes of low back disorders. Vibration
      was measured on 54 worker-days in five heavy industries, with data collected on
      observed and self-reported driving conditions, demographics, and vehicle
      characteristics. Variables significant at p < 0.1 in simple linear regressions
      (20 of 34) were retained for mixed effects multiple regressions to determine the
      best prediction of rms vibration level and 8-h equivalent vibration exposure.
      Vibration was measured, on average, for 205 min per work shift (SD 105). Means
      and standard deviations in m . s-2 were: x-axis 0.35 (0.19); y-axis 0.34 (0.28);
      z-axis 0.54 (0.23); vector sum 0.90 (0.49); and 8-h equivalent vector sum 0.70
      (0.37). The final three regression models retained only 2 or 3 of the 34
      variables (driving speed (<20 km/h and/or 20-40 km/h) and industry and/or vehicle
      type and explained up to 60% of the variance (R2 = 0.26-0.6). PRACTITIONER
      SUMMARY: The purpose of the project was to create a model that can predict whole
      body vibration exposure from a number of observed or self-reported variables.
      This could eliminate the need for costly and time-consuming field measurements of
      WBV in epidemiological studies. Despite a large number of variables included in
      the model (34) and 54 worker-days of WBV measurement, the final models contained
      only two or three variables, and explained 60% of the variance. While this is an
      improvement over use of job title in epidemiological studies, it still leaves a
      considerable amount of WBV variance unexplained.

PMID- 22397359
TI  - Use of synchrotron XANES and Cr-doped coal to further confirm the vaporization of
      organically bound Cr and the formation of chromium(VI) during coal oxy-fuel
      combustion.
AB  - Through the use of synchrotron XANES and Cr-doped brown coal, extensive efforts
      have been made to clarify the volatility of organically bound Cr during oxy-fuel
      combustion and the mode of occurrence and leachability of Cr in resulting fly
      ashes. As the continuation of our previous study using raw coal, the Cr-doped
      coal has been tested in this study to improve the signal-to-noise ratio for Cr K
      edge XANES spectra, and hence the accuracy for Cr(VI) quantification. As has been
      confirmed, the abundant CO(2) as a balance gas for oxy-firing has the potential
      to inhibit the decomposition of organically bound Cr, thereby favoring its
      retention in solid ash. It also has the potential to promote the oxidation of
      Cr(III) to Cr(VI) to a minor extent. Increasing the oxygen partial pressure,
      particularly in the coexistence of HCl in flue gas, favored the oxidation of
      Cr(III) into gaseous Cr(VI)-bearing species such as CrO(2)Cl(2). Regarding the
      solid impurities including Na(2)SO(4) and CaO, Na(2)SO(4) has proven to
      preferentially capture the Cr(III)-bearing species at a low furnace temperature
      such as 600  degrees C. Its promoting effect on the oxidation of Cr(III) to
      Cr(VI), although thermodynamically available at the temperatures examined here,
      is negligible in a lab-scale drop tube furnace (DTF), where the particle
      residence time is extremely short. In contrast, CaO has proven facilitating the
      capture of Cr(VI)-bearing species particularly oxychloride vapors at 1000 
      degrees C, forming Ca chromate with the formulas of CaCrO(4) and Ca(3)(CrO(4))(2)
      via a direction stabilization of Cr(VI) oxychloride vapor by CaO particle or an
      indirect oxidation of Cr(III) via the initial formation of Ca chromite. The fly
      ash collected from the combustion of Cr-doped coal alone has a lower water
      solubility (i.e., 58.7%) for its Cr(VI) species, due to the formation of Ba/Pb
      chromate and/or the incorporation of Cr(VI) vapor into a slagging phase which is
      water-insoluble. Adding CaO to coal increased the water-solubility of both Cr(VI)
      and Cr(III) by forming Ca chromite and chromate, respectively.

PMID- 22397360
TI  - ENMD-2076  for hematological malignancies.
AB  - INTRODUCTION: Aurora kinases are key regulators of mitosis and inhibition of
      Aurora kinase activity is a rational therapeutic strategy in the treatment of
      solid tumors and hematological malignancies. AREAS COVERED: This paper will
      provide an updated summary of preclinical and clinical experience with ENMD-2076
      in hematological malignancies. The MEDLINE (OVID) (1980 through 31 January 2012)
      was searched with the term combinations including Aurora, multiple myeloma,
      leukemia, lymphoma, myelodysplastic syndrome and myeloproliferative neoplasms. In
      addition, the American Society of Clinical Oncology (ASCO) (1997 - 2011) and the
      American Society of Hematology (ASH) (1997 - 2011) conference proceedings were
      searched for reports of new or ongoing trials. EXPERT OPINION: ENMD-2076 is a
      multi-kinase inhibitor, with activity against Aurora A kinase, FLT3, c-KIT, c-FMS
      and VEGFR-2 and -3. It appears to be tolerable, exhibits favorable
      pharmacokinetic profiles and has activity in patients with acute myeloid leukemia
      and multiple myeloma. Further evaluation with cytotoxic chemotherapy and targeted
      agents, which affect different pathways and have non-overlapping toxicities, in
      patients with hematological malignancies are warranted.

PMID- 22397361
TI  - The PI3K/Akt pathway is required for LPS activation of microglial cells.
AB  - Upregulation of inflammatory responses in the brain is associated with a number
      of neurodegenerative diseases. Microglia are activated in neurodegenerative
      diseases, producing pro-inflammatory mediators. Critically, lipopolysaccharide
      (LPS)-induced microglial activation causes dopaminergic neurodegeneration in
      vitro and in vivo. The signaling mechanisms triggered by LPS to stimulate the
      release of pro-inflammatory mediators in microglial cells are still incompletely
      understood. To further explore the mechanisms of LPS-mediated inflammatory
      response of microglial cells, we studied the role of phosphatidylinositol 3
      kinase (PI3K)/Akt signal transduction pathways known to be activated by toll-like
      receptor-4 signaling through LPS. In the current study, we report that the
      activation profile of LPS-induced pAkt activation preceded those of LPS-induced
      NF-kappaB activation, suggesting a role for PI3K/Akt in the pathway activation of
      NF-kappaB-dependent inflammatory responses of activated microglia. These results,
      providing the first evidence that PI3K dependent signaling is involved in the
      inflammatory responses of microglial cells following LPS stimulation, may be
      useful in preventing inflammatory based neurodegenerative processes.

PMID- 22397362
TI  - Immunolocalization of RANK and RANKL along the root surface and in the
      periodontal membrane of human primary and permanent teeth.
AB  - OBJECTIVE: Root resorption, impaired tooth eruption and early tooth loss have
      been described in relation to diseases that involve defects in the RANK-RANKL-OPG
      expression. The aim of the present immunhistochemical study was to localize and
      compare the reactions for RANK and membrane-bound RANKL along root surfaces and
      in the periodontal membrane in close proximity to the root surface of human
      primary and permanent teeth. MATERIALS AND METHODS: The material comprised
      extracted human teeth (11 primary teeth and six permanent teeth) from 10
      different patients. Paraffin sections were prepared of each tooth and sections of
      each tooth were immunohistochemically stained with antibodies specific for
      membrane-bound RANKL and RANK. RESULTS: The root surface and the periodontal
      membrane in close proximity to the root surface did not show immunoreactivity for
      RANKL. RANKL was only located in odontoblasts and in cells along denticles in one
      primary tooth. RANK was located in mononuclear cells in the pulp and in
      multinucleated odontoclasts along resorbed root surfaces and along resorbed
      dentin surfaces in the pulp in primary teeth and one permanent tooth.
      CONCLUSIONS: This study demonstrated RANK positivity in resorption areas in
      primary and permanent teeth. RANKL was positive in the pulp of one primary tooth.
      RANK expression in odontoclasts and RANKL expression in the pulp may indicate
      that RANK/RANKL play a role during resorption.

PMID- 22397363
TI  - Organic transistors with ordered nanoparticle arrays as a tailorable platform for
      selective, in situ detection.
AB  - The use of organic transistors as sensing platforms provides a number of distinct
      advantages over conventional detection technologies, including their tunability,
      portability, and ability to directly transduce binding events without tedious and
      expensive labeling procedures. However, detection efforts using organic
      transistors lack a general method to uniquely specify and detect a target of
      interest. While highly sensitive liquid- and vapor-phase sensors have been
      previously reported, detection has been restricted either to the serendipitous
      interaction of the analyte molecules with the organic semiconductor or to the
      covalent functionalization of the semiconductor with receptor groups to enhance
      specificity. However, the former technique cannot be regularly relied upon for
      tailorable sensing while the latter may result in unpredictable decreases in
      electronic performance. Thus, a method to provide modular receptor sites on the
      surface of an organic transistor without damaging the device will significantly
      advance the field, especially regarding biological species detection. In this
      work, we utilized a block copolymer to template ordered, large-area arrays of
      gold nanoparticles, with sub-100 nm center-to-center spacing onto the surface of
      an organic transistor. This highly modular platform is designed for orthogonal
      modification with a number of available chemical and biological functional groups
      by taking advantage of the well-studied gold-thiol linkage. Herein, we
      demonstrate the functionalization of gold nanoparticles with a mercury-binding
      oligonucleotide sequence. Finally, we demonstrate the highly selective and robust
      detection of mercury(II) using this platform in an underwater environment.

PMID- 22397365
TI  - Molecular alterations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2)
      metabolic genes and additional genetic mutations in newly diagnosed acute myeloid
      leukemia patients.
AB  - BACKGROUND: Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) metabolic genes
      encode cytosolic and mitochondrial enzymes that catalyze the conversion of
      isocitrate to alpha-ketoglutarate. Acquired somatic mutations of IDH1 and IDH2
      have recently been reported in some types of brain tumors and a small proportion
      of acute myeloid leukemia (AML) cases. METHODS: Two-hundred and thirty newly
      diagnosed AML patients were analyzed for the presence of IDH1 and IDH2
      heterozygous mutations by polymerase chain reaction-denaturing high performance
      liquid chromatography (PCR-DHPLC) followed by direct sequencing. Clinical and
      biological characteristics were analyzed and correlated to the IDH mutational
      status. Coexisting mutations such as FLT3, PML-RARA, RAS, AML1, and NPM1
      mutations were additionally explored. RESULTS: The prevalence of IDH1 and IDH2
      mutations was 8.7% (20/230) and 10.4% (24/230), respectively. Six missense
      mutations were identified among IDH1-mutated cases; p.R132H (n = 8), p.R132C (n =
      6), p.R132S (n = 2), p.R132G (n = 2), p.R132L (n = 1), and p.I99M (n = 1). Two
      missense mutations were found in IDH2-mutated cases; p.R140Q (n = 20) and p.R172K
      (n = 4). No patients had dual IDH1 and IDH2 mutations. About 18% of AML with
      normal cytogenetics and 31% of acute promyelocytic leukemia had IDH mutations.
      Half of the IDH-mutated cohort had normal karyotype and the major FAB subtype was
      AML-M2. Interestingly, IDH1- and IDH2-mutated cases predominantly had NPM1
      mutations (60-74%) as compared to the wild type (P < 0.001). Very few IDH-mutated
      cases had FLT3 and/or RAS abnormalities and none of them had AML1 mutations.
      Older age and higher median platelet counts were significantly associated with
      IDH2 mutations although the clinical impact of either IDH1 or IDH2 mutations on
      patients' overall survival could not be observed. CONCLUSION: Overall, 19% of
      newly diagnosed AML patients had alterations of IDH genes. No patients
      concurrently carried both IDH1 and IDH2 mutations suggesting that these mutations
      were mutually exclusive. NPM1 mutation appears as a major coexisting genetic
      mutation in IDH-mutated patients. Our present data failed to support the
      prognostic relevance of IDH mutations although alterations of these metabolic
      genes potentially have an important role in leukemia development.

PMID- 22397366
TI  - Who fans the flames of Alzheimer's disease brains? Misfolded tau on the crossroad
      of neurodegenerative and inflammatory pathways.
AB  - Neurodegeneration, induced by misfolded tau protein, and neuroinflammation,
      driven by glial cells, represent the salient features of Alzheimer's disease (AD)
      and related human tauopathies. While tau neurodegeneration significantly
      correlates with disease progression, brain inflammation seems to be an important
      factor in regulating the resistance or susceptibility to AD neurodegeneration.
      Previously, it has been shown that there is a reciprocal relationship between the
      local inflammatory response and neurofibrillary lesions. Numerous independent
      studies have reported that inflammatory responses may contribute to the
      development of tau pathology and thus accelerate the course of disease. It has
      been shown that various cytokines can significantly affect the functional and
      structural properties of intracellular tau. Notwithstanding, anti-inflammatory
      approaches have not unequivocally demonstrated that inhibition of the brain
      immune response can lead to reduction of neurofibrillary lesions. On the other
      hand, our recent data show that misfolded tau could represent a trigger for
      microglial activation, suggesting the dual role of misfolded tau in the
      Alzheimer's disease inflammatory cascade. On the basis of current knowledge, we
      can conclude that misfolded tau is located at the crossroad of the
      neurodegenerative and neuroinflammatory pathways. Thus disease-modified tau
      represents an important target for potential therapeutic strategies for patients
      with Alzheimer's disease.

PMID- 22397367
TI  - Ezrin phosphorylation on tyrosine 477 regulates invasion and metastasis of breast
      cancer cells.
AB  - BACKGROUND: The membrane cytoskeletal crosslinker, ezrin, a member of the ERM
      family of proteins, is frequently over-expressed in human breast cancers, and is
      required for motility and invasion of epithelial cells. Our group previously
      showed that ezrin acts co-operatively with the non-receptor tyrosine kinase, Src,
      in deregulation of cell-cell contacts and scattering of epithelial cells. In
      particular, ezrin phosphorylation on Y477 by Src is specific to ezrin within the
      ERM family, and is required for HGF-induced scattering of epithelial cells. We
      therefore sought to examine the role of Y477 phosphorylation in ezrin on tumor
      progression. METHODS: Using a highly metastatic mouse mammary carcinoma cell line
      (AC2M2), we tested the effect of over-expressing a non-phosphorylatable form of
      ezrin (Y477F) on invasive colony growth in 3-dimensional Matrigel cultures, and
      on local invasion and metastasis in an orthotopic engraftment model. RESULTS:
      AC2M2 cells over-expressing Y477F ezrin exhibited delayed migration in vitro, and
      cohesive round colonies in 3-dimensional Matrigel cultures, compared to control
      cells that formed invasive colonies with branching chains of cells and numerous
      actin-rich protrusions. Moreover, over-expression of Y477F ezrin inhibits local
      tumor invasion in vivo. Whereas orthotopically injected wild type AC2M2 tumor
      cells were found to infiltrate into the abdominal wall and visceral organs within
      three weeks, tumors expressing Y477F ezrin remained circumscribed, with little
      invasion into the surrounding stroma and abdominal wall. Additionally, Y477F
      ezrin reduces the number of lung metastatic lesions. CONCLUSIONS: Our study
      implicates a role of Y477 ezrin, which is phosphorylated by Src, in regulating
      local invasion and metastasis of breast carcinoma cells, and provides a
      clinically relevant model for assessing the Src/ezrin pathway as a potential
      prognostic/predictive marker or treatment target for invasive human breast
      cancer.

PMID- 22397369
TI  - Scalable synthesis of highly reactive 1,3-diamino dienes from vinamidinium salts
      and their use in Diels-Alder reactions.
AB  - A practical and chromatography-free synthesis of vinamidinium salts and their use
      as diene precursors in Diels-Alder reactions is reported. Additionally, 1,3
      dipyrrolidino-1,3-butadiene was shown to be significantly more reactive than
      Rawal's diene in a competition experiment.

PMID- 22397368
TI  - Postchallenge responses of nitrotyrosine and TNF-alpha during 75-g oral glucose
      tolerance test are associated with the presence of coronary artery diseases in
      patients with prediabetes.
AB  - BACKGROUND: Meta-analysis has demonstrated an exponential relationship between 2
      hr postchallenge hyperglycemia and coronary artery disease (CAD). Pulsatile
      hyperglycemia can acutely increase proinflammatory cytokines by oxidative stress.
      We hypothesized that postchallenge proinflammatory and nitrosative responses
      after 75 g oral glucose tolerance tests (75 g-OGTT) might be associated with CAD
      in patients without previously recognized type 2 diabetes mellitus (T2DM).
      METHODS: Serial changes of plasma glucose (PG), tumor necrosis factor-alpha (TNF
      alpha), interleukin-6 (IL-6) and nitrotyrosine levels were analyzed during 75 g
      OGTT in 120 patients (81 male; age 62 +/- 11 years) before coronary angiography.
      Patients were classified as normal (NGT; 42%), impaired (IGT; 34%) and diabetic
      (T2DM; 24%) glucose tolerance by 75 g-OGTT. RESULTS: Postchallenge hyperglycemia
      elicited TNF-alpha, IL-6 and nitrotyrosine levels time-dependently, and 2-hr
      median levels of TNF-alpha (7.1 versus 6.4 pg/ml; P < 0.05) and nitrotyrosine
      (1.01 versus 0.83 MUmol/l; P < 0.05), but not IL-6 or PG, were significantly
      higher in patients with CAD in either IGT or T2DM groups. After adjusting risk
      factors and glucose tolerance status, 2-hr nitrotyrosine in highest quartiles
      (OR: 3.1, P < 0.05) remained an independent predictor of CAD by logistic
      regression analysis. CONCLUSIONS: These results highlight postchallenge
      proinflammatory and nitrosative responses by 75 g-OGTT, rather than hyperglycemia
      per se, are associated with CAD in patients without previous recognized diabetes.

PMID- 22397370
TI  - Partial biodistribution and pharmacokinetics of isoniazid and rifabutin following
      pulmonary delivery of inhalable microparticles to rhesus macaques.
AB  - Dry powder inhalations (DPI) of microparticles containing isoniazid (INH) and
      rifabutin (RFB) are under preclinical development for use in pulmonary
      tuberculosis. Microparticles containing 0.25, 2.5, or 25 mg of each drug were
      administered daily for 90 days to rhesus macaques (n = 4/group). Single
      inhalations or intravenous (i.v.) doses were administered to separate groups.
      Drugs in serum, alveolar macrophages, and organ homogenates were assayed by high
      performance liquid chromatography (HPLC). The RFB/INH in the lungs (101.10 +/-
      12.90/101.07 +/- 8.09 MUg/g of tissue) was twice that of the liver concentrations
      (60.22 +/- 04.97/52.08 +/- 4.62 MUg/g) and four times that of the kidneys (22.89
      +/- 05.22/30.25 +/- 3.71 MUg/g). Pharmacokinetic parameters indicated the
      operation of flip-flop kinetics. Thus, the elimination half-life (t(1/2)) of RFB
      and INH was calculated as 8.01 +/- 0.5 and 2.49 +/- 0.23 h, respectively, upon
      intravenous (iv) administration, and as 13.8 +/- 0.8 and 10.43 +/- 0.77 h
      following a single inhalation; or 13.36 +/- 3.51 and 10.13 +/- 3.01 at a presumed
      steady state (day 60 of dosing). Targeted and sustained drug delivery to nonhuman
      primate lungs and alveolar macrophages was demonstrated. Flip-flop serum
      pharmacokinetics was observed, and nonlinearity in some pharmacokinetic
      parameters at logarithmic dose increments was indicated. The results suggest that
      human patients would benefit through improvement in biodistribution following
      DPI.

PMID- 22397372
TI  - Growth of p-type hematite by atomic layer deposition and its utilization for
      improved solar water splitting.
AB  - Mg-doped hematite (alpha-Fe(2)O(3)) was synthesized by atomic layer deposition
      (ALD). The resulting material was identified as p-type with a hole concentration
      of ca. 1.7 * 10(15) cm(-3). When grown on n-type hematite, the p-type layer was
      found to create a built-in field that could be used to assist
      photoelectrochemical water splitting reactions. A nominal 200 mV turn-on voltage
      shift toward the cathodic direction was measured, which is comparable to what has
      been measured using water oxidation catalysts. This result suggests that it is
      possible to achieve desired energetics for solar water splitting directly on
      metal oxides through advanced material preparations. Similar approaches may be
      used to mitigate problems caused by energy mismatch between water redox
      potentials and the band edges of hematite and many other low-cost metal oxides,
      enabling practical solar water splitting as a means for solar energy storage.

PMID- 22397371
TI  - Structure-based analysis of VDAC1: N-terminus location, translocation, channel
      gating and association with anti-apoptotic proteins.
AB  - Structural studies place the VDAC1 (voltage-dependent anion channel 1) N-terminal
      region within the channel pore. Biochemical and functional studies, however,
      reveal that the N-terminal domain is cytoplasmically exposed. In the present
      study, the location and translocation of the VDAC1 N-terminal domain, and its
      role in voltage-gating and as a target for anti-apoptotic proteins, were
      addressed. Site-directed mutagenesis and cysteine residue substitution, together
      with a thiol-specific cross-linker, served to show that the VDAC1 N-terminal
      region exists in a dynamic equilibrium, located within the pore or exposed
      outside the beta-barrel. Using a single cysteine-residue-bearing VDAC1, we
      demonstrate that the N-terminal region lies inside the pore. However, the same
      region can be exposed outside the pore, where it dimerizes with the N-terminal
      domain of a second VDAC1 molecule. When the N-terminal region alpha-helix
      structure was perturbed, intra-molecular cross-linking was abolished and
      dimerization was enhanced. This mutant also displays reduced voltage-gating and
      reduced binding to hexokinase, but not to the anti-apoptotic proteins Bcl-2 and
      Bcl-xL. Replacing glycine residues in the N-terminal domain GRS (glycine-rich
      sequence) yielded less intra-molecular cross-linked product but more
      dimerization, suggesting that GRS provides the flexibility needed for N-terminal
      translocation from the internal pore to the channel face. N-terminal mobility may
      thus contribute to channel gating and interaction with anti-apoptotic proteins.

PMID- 22397373
TI  - Appraisal of radioactivity and associated radiation hazards in sand samples of
      four rivers of Punjab province, Pakistan.
AB  - Natural and anthropogenic radioactivity of sand and water samples collected from
      the four big rivers of Punjab province, Pakistan, was measured using a high
      purity germanium detector coupled with a high resolution multichannel analyser.
      The average concentration of the naturally occurring radionuclides (226)Ra,
      (232)Th and (40)K in all the sand samples from the rivers Jhelum, Chenab, Ravi
      and Indus was found to be 22+/-0.6, 36+/-1 and 287+/-10 Bq kg (-1), respectively,
      while the concentration of the anthropogenic radionuclide (137)Cs was found to be
      below the minimum detectable activity, i.e. ~1.2 Bq kg (-1). All the sand samples
      have Ra(eq) concentrations lower than the limit of 370 Bq kg (-1). Indoor (H
      (in)) and outdoor (H (out)) radiation hazard indices were calculated for the
      samples to assess the radiation hazards arising due to the use of this sand in
      construction, and were found to be less than unity in the study area. Calculated
      values of the absorbed dose rate were less than the typical world average value
      of 59 nGy h (-1), and the annual effective dose rate was also less than the
      typical world value of 70 MUSv, except in the Indus river, in which it is
      slightly higher then the world average. Results show that the measured values are
      comparable with other global radioactivity measurements. None of the studied
      riverbeds was considered a radiological hazard, and their sand can be safely used
      in construction.

PMID- 22397374
TI  - Taxonomic status of Chinese bahaba (Bahaba taipingensis) and its phylogenetic
      relationship with other species in the family Sciaenidae.
AB  - Sciaenidae is one of the largest fish families, but the phylogeny and taxonomy of
      these fishes are still being disputed. Furthermore, the taxonomic status of the
      Chinese bahaba (Bahaba taipingensis), which is an endemic species to China, had
      never been studied through molecular method. In this study, phylogenetic
      relationships among sciaenid species were reconstructed using DNA sequence data
      from the mitochondrial cytochrome b (cyt b) gene and the 16S ribosomal RNA (16S
      rRNA) gene through Bayesian inference (BI) analyses. The phylogenetic trees
      indicated that the Chinese bahaba closely related to Collichthys and
      Pseudosciaena. Previous studies (Meng et al. 2004. Prog Nat Sci 14(5):514-521,
      [in Chinese]) showed that the subfamily Pseudosciaeninae represented the latest
      evolutionary sort, which was more suitable with the current environment. Based on
      our 16S rRNA, the Chinese bahaba showed close relationship with Pseudosciaena,
      thus the divergence of the Chinese bahaba maybe also very late within the family
      Sciaenidae. It was probably that the oceanographic or ecological discontinuities
      of these species vary considerably causing particularly strong breaks.
      Furthermore, combined with previous studies, we suggested that there was only one
      genus, Otolithes, within the subfamily Otolithinae. Nevertheless, the taxonomic
      status of the Chinese bahaba and the phylogeny of the whole family were not
      completely solved. Additional samples of more species are required to develop a
      clearer picture of the evolutionary history of Sciaenidae.

PMID- 22397375
TI  - Genetic structuring of European anchovy (Engraulis encrasicolus) populations
      through mitochondrial DNA sequences.
AB  - Mitochondrial DNA sequence variation in 655 bpfragments of the cytochrome oxidase
      c subunit I gene, known as the DNA barcode, of European anchovy (Engraulis
      encrasicolus) was evaluated by analyzing 1529 individuals representing 16
      populations from the Black Sea, through the Marmara Sea and the Aegean Sea to the
      Mediterranean Sea. A total of 19 (2.9%) variable sites were found among
      individuals, and these defined 10 genetically diverged populations with an
      overall mean distance of 1.2%. The highest nucleotide divergence was found
      between samples of eastern Mediterranean and northern Aegean (2.2%). Evolutionary
      history analysis among 16 populations clustered the Mediterranean Sea clades in
      one main branch and the other clades in another branch. Diverging pattern of the
      European anchovy populations correlated with geographic dispersion supports the
      genetic structuring through the Black Sea-Marmara Sea-Aegean Sea-Mediterranean
      Sea quad.

PMID- 22397376
TI  - The evolution of the mitochondrial genetic code in arthropods revisited.
AB  - A variant of the invertebrate mitochondrial genetic code was previously
      identified in arthropods (Abascal et al. 2006a, PLoS Biol 4:e127) in which,
      instead of translating the AGG codon as serine, as in other invertebrates, some
      arthropods translate AGG as lysine. Here, we revisit the evolution of the genetic
      code in arthropods taking into account that (1) the number of arthropod
      mitochondrial genomes sequenced has triplicated since the original findings were
      published; (2) the phylogeny of arthropods has been recently resolved with
      confidence for many groups; and (3) sophisticated probabilistic methods can be
      applied to analyze the evolution of the genetic code in arthropod mitochondria.
      According to our analyses, evolutionary shifts in the genetic code have been more
      common than previously inferred, with many taxonomic groups displaying two
      alternative codes. Ancestral character-state reconstruction using probabilistic
      methods confirmed that the arthropod ancestor most likely translated AGG as
      lysine. Point mutations at tRNA-Lys and tRNA-Ser correlated with the meaning of
      the AGG codon. In addition, we identified three variables (GC content, number of
      AGG codons, and taxonomic information) that best explain the use of each of the
      two alternative genetic codes.

PMID- 22397377
TI  - Complete mitochondrial genome of Oxuderces dentatus (Perciformes, Gobioidei).
AB  - The complete mitochondrial genome (mitogenome) of Oxuderces dentatus was
      determined first. The genome was 17,116 bp in length and consisted of 13 protein
      coding genes, 22 tRNA genes, 2 ribosomal RNA genes, and 2 main non-coding regions
      [the control region (CR) and the origin of the light strand replication], the
      gene composition and order of which was similar to most other vertebrates. The
      overall base composition of the heavy strand was T 27.9%, C 26.8%, A 30.2%, and G
      15.1%, with a slight A+T bias of 58.1%. In addition to the discrete and conserved
      sequence blocks, unusual long tandem repeat unit (three 150-bp tandem repeat
      units and an incomplete copy of 146 bp) was also detected within CR. This
      mitogenome sequence data would play an important role in population genetics and
      phylogenetic analysis of the Gobioidei.

PMID- 22397378
TI  - Mitochondrial genome of Onychostoma lini (Teleostei, Cypriniformes).
AB  - The complete mitogenome sequence of a vulnerable species Onychostoma lini was
      determined using polymerase chain reaction and directly sequenced with primer
      walking method. The complete mitogenome was 16,595 bp in length, containing 37
      genes of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a control
      region (D-loop). The gene order and composition of O. lini was similar to most
      other fishes. The descending order of the base composition on heavy strand was
      31.6% A, 27.9% C, 24.6% T, and 15.9% G, with a relatively lower level of G and a
      slight AT bias of 56.2%. The codon usage followed the typical vertebrate
      mitochondrial pattern (ATG or GTG for start codon and TAA or TAG for stop codon).
      The complete mitogenome sequence of O. lini provides fundamental data for further
      conversation genetics and captive breeding studies on this species.

PMID- 22397379
TI  - Polymorphisms in genes encoding mt-tRNA in female breast cancer in Poland.
AB  - Recently, there have been indications of participation of mitochondria in the
      carcinogenic process and the role of polymorphisms in increasing the risk of
      cancer. The aim of the study was to detect possible changes in the sequence of 22
      genes encoding mitochondrial tRNA in breast cancer carcinoma, which take part in
      protein synthesis in the translation process. The analysis of tumour tissue and
      blood material sampled from 50 patients revealed that few mutations have been
      found. It cannot be excluded that, through their impact on the secondary and
      tertiary tRNA structure, polymorphisms may cause mitochondrial dysfunction and
      contribute to appearance of other changes in mtDNA. Mutations in tRNA genes in
      breast cancer may affect the cell and cause its dysfunction, as in mitochondrial
      diseases.

PMID- 22397380
TI  - The complete mitochondrial genome of sable, Martes zibellina.
AB  - The complete mitogenome sequence of the Sable (NC_011579) was determined using
      long PCR (Polymerase Chain Reaction). The genome was 16,523 bp in length and
      contained 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 1 control
      region. The gene composition and order of which was similar to most other
      mammals. The overall base composition of the heavy strand in descending order is
      A (32.0%), C (27. 6%), T (25.8%) and G (14.7%). The base compositions present
      clearly the A-C skew, which is most obviously in the control region and protein
      coding genes. The extended termination-associated sequence domain, the central
      conserved domain, and the conserved sequence block domain are defined in the
      mitochondrial genome control region of Sable. This mitogenome sequence data would
      play an important role in phylogenetics and systematics of Martes zibellina.

PMID- 22397381
TI  - Authentication of Angelica anomala Ave-Lall cultivars through DNA barcodes.
AB  - Angelica anomala Ave-Lall (Chuanbaizhi in Chinese) is an important medicinal
      plant which can be used in traditional Chinese medicines; however, there are no
      authentic and universal methods to differentiate this Sichuan famous-region drug
      of A. anomala from a large number of non-famous-region and false drugs. It has
      been demonstrated that DNA barcoding is a molecular diagnostic method for species
      identification, which uses a single standardized DNA fragment. In this study, we
      tested five DNA barcoding candidates (matK, ITS, ITS2, rbcL, and psbA-trnH), and
      we found that ITS was the best candidate to authenticate the famous-region drug
      of A. anomala. Moreover, through comparative analysis of these five DNA barcodes
      between A. anomala and Angelica dahurica, we found that ITS had the most and ITS2
      had more variable regions, but the psbA-trnH, rbcL, and matK regions were
      identical. Hence, we suggest ITS as the DNA barcoding to identify A. anomala and
      A. dahurica. Moreover, we are determined to adopt the A. anomala as the accurate
      Latin name of Chuanbaizhi.

PMID- 22397382
TI  - Complete mitochondrial genome of Trypauchen vagina (Perciformes, Gobioidei).
AB  - The complete mitochondrial genome of Trypauchen vagina was determined first. The
      genome is 16,686 bp in length and consists of 13 protein-coding genes, 22 tRNA
      genes, 2 ribosomal RNA genes, and 2 main non-coding regions [the control region
      (CR) and the origin of the light strand replication], the gene composition and
      order of which was similar to most other vertebrates. The overall base
      composition of T. vagina is T 27.6%, C 27.6%, A 29.5%, and G 15.3%, with a slight
      A+T bias of 57.1%. In addition to the discrete and conserved sequence blocks, an
      incomplete tandem repeat unit is detected within the CR. This mitogenome sequence
      data would play an important role in population genetics and phylogenetic
      analysis of the Gobioidei.

PMID- 22397383
TI  - Complete mitochondrial genome of Saunders's gull Chroicocephalus saundersi
      (Charadriiformes, Laridae).
AB  - Saunders's gull Chroicocephalus saundersi (Aves, Charadriiformes, Laridae) is a
      small-sized gull having black-colored head. In this study, the entire
      mitochondrial genome of C. saundersi is sequenced, which is 16,725 bp in length.
      The detailed characteristics of the mitochondrial genome are described here.

PMID- 22397384
TI  - Complete mitochondrial genome of the Chinese oriental vole Eothenomys chinensis
      (Rodentia: Arvicolinae).
AB  - The Chinese oriental vole (Eothenomys chinensis) belongs to subfamily
      Arvicolinae, which is endemic to the mountains in southwest China. E. chinensis
      and other Arvicoline species display a number of features that make them ideal
      for evolutionary studies of speciation and the role of Quaternary glacial cycles
      on diversification. In this study, the complete mitochondrial genome of E.
      chinensis was sequenced. It was determined to be 16,362 bases. The nucleotide
      sequence data of 12 heavy-strand protein-coding genes of E. chinensis and other
      19 rodents were used for phylogenetic analyses. Trees constructed using three
      different phylogenetic methods (Bayesian, maximum parsimony, and maximum
      likelihood) showed a similar topology demonstrating that E. chinensis was
      clustered in subfamily arvicolinae--formed a solid monophyletic group being
      sister to the subfamily Cricetinae. And the trees also suggested that E.
      chinensis is a sister to the genus Microtus and Proedromys.

PMID- 22397385
TI  - The Strain Index (SI) and Threshold Limit Value (TLV) for Hand Activity Level
      (HAL): risk of carpal tunnel syndrome (CTS) in a prospective cohort.
AB  - A cohort of 536 workers was enrolled from 10 diverse manufacturing facilities and
      was followed monthly for six years. Job physical exposures were individually
      measured. Worker demographics, medical history, psychosocial factors, current
      musculoskeletal disorders (MSDs) and nerve conduction studies (NCS) were
      obtained. Point and lifetime prevalence of carpal tunnel syndrome (CTS) at
      baseline (symptoms + abnormal NCS) were 10.3% and 19.8%. During follow-up, there
      were 35 new CTS cases (left, right or both hands). Factors predicting development
      of CTS included: job physical exposure (American conference of governmental
      industrial hygienists Threshold Limit Value (ACGIH TLV) for Hand Activity Level
      (HAL) and the Strain Index (SI)), age, BMI, other MSDs, inflammatory arthritis,
      gardening outside of work and feelings of depression. In the adjusted models, the
      TLV for HAL and the SI were both significant per unit increase in exposure with
      hazard ratios (HR) increasing up to a maximum of 5.4 (p = 0.05) and 5.3 (p =
      0.03), respectively; however, similar to other reports, both suggested lower risk
      at higher exposures. Data suggest that the TLV for HAL and the SI are useful
      metrics for estimating exposure to biomechanical stressors. PRACTITIONER SUMMARY:
      This study was conducted to determine how well the TLV for HAL and the SI predict
      risk of CTS using a prospective cohort design with survival analysis. Both the
      TLV for HAL and the SI were found to predict risk of CTS when adjusted for
      relevant covariates.

PMID- 22397386
TI  - Orthodontic treatment efficiency with self-ligating and conventional edgewise
      twin brackets: a prospective randomized clinical trial.
AB  - OBJECTIVE: To conduct a prospective and randomized study of the efficiency of
      orthodontic treatment with self-ligating edgewise brackets (SL; Time2 brand,
      American Orthodontics) and conventional edgewise twin brackets (CE; Gemini brand,
      3M). MATERIALS AND METHODS: One hundred consecutive patients were randomized to
      treatment with either SL or CE brackets. The participants were treated by one of
      three specialists in orthodontics and with continuous instructions alternately by
      five orthodontic assistants according to our normal treatment routine (ie,
      modified 0.022" MBT preadjusted edgewise technique). The treatments were
      evaluated in terms of overall treatment time, number of visits, and treatment
      outcome using the Index of Complexity, Outcome and Need (ICON). The number of
      emergency appointments, number of archwires, overjet, relative space, and
      extractions at treatment start were noted. RESULTS: After dropouts, the analyzed
      material consisted of 44 patients treated with SL (mean age 15.3 years, mean ICON
      60.7, 70.4% female) and 46 patients treated with CE (mean age 15.0 years, mean
      ICON 56.5, 71.7% female). There were no statistically significant differences
      between the SL and CE groups in terms of mean treatment time in months (20.4 vs
      18.2), mean number of visits (15.5 vs 14.1), mean ICON scores after treatment
      (13.2 vs 11.9), or mean ICON improvement grade (7.9 vs 9.1). CONCLUSION:
      Orthodontic treatment with SL brackets does not reduce treatment time or number
      of appointments and does not affect posttreatment ICON scores or ICON improvement
      grade compared with CE brackets.

PMID- 22397387
TI  - Odontometric evaluation of mandibular premolars with tooth shape deviation: a
      case-control study.
AB  - OBJECTIVE: To evaluate the mean dimensions and morphologic characteristics of
      mandibular premolars that had mesiodistally elongated and faciolingually squeezed
      tooth shape deviations (MnP-TSD) and determine the population prevalence of this
      anomaly. MATERIALS AND METHODS: Clinical photographs and study models were made
      for all new patients with MnP-TSD teeth who were seen over 20 years. The
      mesiodistal (MD) and faciolingual (FL) dimensions of the anomalous premolars were
      measured. MD/FL indices and MD * FL mm(2) occlusal crown areas were calculated
      and means and standard deviations were derived. Male and female means from the
      mandibular first and second anomalous premolars (MnP1/MnP2-TSD) were
      statistically compared against gender-specific means derived from published
      normative data using Student's t-tests and chi-square tests. RESULTS: Fifty-six
      individuals (33 male and 23 female) with MnP-TSD were identified, giving a male
      to female ratio of 1.4:1, while the prevalence rate in the indigenous British
      population was estimated to be 0.6%. The MD widths of the MnP1-TSD and MnP2-TSD
      teeth were approximately 1 mm wider than normal, while the FL diameters were
      about 0.5 mm and 1.5 mm narrower respectively, for the first and second premolar
      teeth. The MD/FL indices, instead of being under 90 as usual were above 100,
      while the mean MD/FL mm(2) crown surface areas were normal. CONCLUSIONS: This
      study supplies odontometric dimensional and morphologic data on MnP-TSD teeth
      that provide a reference source for future comparisons.

PMID- 22397388
TI  - Sweet block copolymer nanoparticles: preparation and self-assembly of fully
      oligosaccharide-based amphiphile.
AB  - The preparation of biocompatible nanocarriers that have potential applications in
      the cosmetic and health industries is highly desired. The self-assembly of
      amphiphilic block copolymers displaying biosourced polysaccharides at the surface
      is one of the most promising approaches. In the continuity of our works related
      to the preparation of "hybrid" amphiphilic oligosaccharide-based block
      copolymers, we present here the design of a new generation of self-assembled
      nanoparticles composed entirely of oligosaccharide-based amphiphilic block co
      oligomers (BCO). These systems are defined by a covalent linkage of the two
      saccharidic blocks through their reducing end units, resulting in a sweet "head
      to-head" connection. As an example, we have prepared and studied a BCO in which
      the hydrophilic part is composed of a free maltoheptaosyl derivative clicked to a
      hydrophobic part composed of a peracetylated maltoheptaosyl derivative. This
      amphiphilic BCO self-assembles to form spherical micelles in water with an
      average diameter of 30 nm. The efficient enzymatic hydrolysis of the
      maltoheptaose that constitutes the shell of the micelles was followed by light
      scattering and colorimetric methods.

PMID- 22397390
TI  - Mild asthmatics benefit from music therapy.
AB  - OBJECTIVE: The aim of the study was to evaluate the effectiveness of pulmonary
      rehabilitation with music therapy in patients with asthma. METHODS: Seventy-six
      selected inpatients (54 women and 22 men; mean age = 56.4 years; SD = 11.8) with
      stable asthma underwent pulmonary rehabilitation in two groups: standard versus
      music therapy. RESULTS: After the intervention, an increase in analyzed
      spirometric values (forced expiratory volume at the first second (FEV(1)), FEV(1)
      as a percentage of vital capacity (FEV(1) % FVC), forced expiratory flow at 25%,
      50%, and 75% of vital capacity (FEF(25), FEF(50), and FEF(75), respectively), and
      peak expiratory flow) was observed in both the groups (p < .05) but without any
      intergroup differences (p > .05). A greater increase of mean FEV(1) % FVC,
      FEF(50), and FEF(75) values was observed only in the patients with mild asthma
      from the music therapy group (p < .05). In both the groups, a dyspnea reduction
      was noted (p < .001). However, it was influenced neither by the type of
      rehabilitation nor by the gender (p > .05), but the interaction of these
      variables was significant (p = .044). A dyspnea reduction was observed in women
      in both the groups (p < .001) and in men in the music therapy group only (p =
      .001). A change in the value of anxiety (6.43, SD = 7.73) on the 10th day
      compared with the first day of the study was noticed (p < .001). However, this
      change was not influenced by the type of rehabilitation, gender, or a combination
      of these two variables (p > .05). CONCLUSION: Music therapy improves the
      respiratory function in patients with mild asthma and reduces dyspnea mainly in
      men with asthma.

PMID- 22397391
TI  - Correlation analysis of atomic and single-molecule junction conductance.
AB  - The break-junction technique is widely used to measure electronic properties of
      nanoscale junctions including metal point-contacts and single-molecule junctions.
      In these measurements, conductance is measured as a function of electrode
      displacement yielding data that is analyzed by constructing conductance
      histograms to determine the most frequently observed conductance values in the
      nanoscale junctions. However much of the rich physics in these measurements is
      lost in this simple analysis technique. Conductance histograms cannot be used to
      study the statistical relation of distinct junction configurations, to
      distinguish structurally different configurations that have similar conductance
      values, or to obtain information on the relation between conductance and junction
      elongation. Here, we give a detailed introduction to a novel statistical analysis
      method based on the two-dimensional cross-correlation histogram (2DCH) analysis
      of conductance traces and show that this method provides new information about
      the relation of different junction configurations that occur during the formation
      and evolution of metal and single-molecule junctions. We first illustrate the
      different types of correlation effects by using simulated conductance traces. We
      then apply this analysis method to several different experimental examples. We
      show from break-junction measurements of different metal point-contacts that in
      aluminum, the first conductance histogram peak corresponds to two different
      junction structures. In tantalum, we identify the frequent absence of adhesive
      instability. We show that conductance plateaus shift in a correlated manner in
      iron and vanadium junctions. Finally, we highlight the applicability of the
      correlation analysis to single-molecule platinum-CO-platinum and gold-4,4'
      bipyridine-gold junctions.

PMID- 22397392
TI  - Use of dairy products, lactose, and calcium and risk of ovarian cancer - results
      from a Danish case-control study.
AB  - BACKGROUND: A number of epidemiological studies have examined the association
      between use of dairy products and risk of ovarian cancer, but results are
      conflicting. Using data from a large Danish population-based case-control study
      we here further examined the association between dairy consumption, lactose, and
      calcium and risk of overall ovarian cancer and histological types of ovarian
      cancer. MATERIAL AND METHODS: In the period 1995-1999 we included 554 women with
      epithelial ovarian cancer and 1554 randomly selected age-matched controls (35-79
      years). All women participated in a detailed personal interview that included
      questions about dairy consumption. Data were analysed using multiple logistic
      regression models. RESULTS: Total dairy intake was associated with ovarian cancer
      risk (OR = 1.11; 95% CI: 1.07-1.15 per 100 ml/day). The association was strongest
      for milk [OR = 1.14; 95% CI: 1.03-1.27 per glass (200 ml)/day], soured milk
      products [OR = 1.49; 95% CI: 1.22-1.81 per portion (250 ml)/day] and yoghurt [OR
      = 1.65; 95% CI: 1.22-2.23 per portion (250 ml)/day]. In contrast, intake of
      cheese was associated with a decreased risk [OR = 0.70; 95% CI: 0.55-0.89 for > 1
      portion (100 ml)/day compared with no intake]. Intake of lactose, but not
      calcium, was also associated with an increased ovarian cancer risk (OR = 1.24;
      95% CI: 1.10-1.40 per 10 g of lactose/day). Similar risk patterns were observed
      for the different histological types of ovarian cancer, indicating virtually
      identical aetiologies with regard to dairy intake, lactose, and calcium.
      CONCLUSIONS: Our results indicate that intake of dairy products is associated
      with a modest increased risk of ovarian cancer. In addition, ovarian cancer
      development was associated with lactose intake.

PMID- 22397393
TI  - Synthesis of alpha-oxycarbanilinophosphonates and their anticholinesterase
      activities: the most potent derivative is bound to the peripheral site of
      acetylcholinesterase.
AB  - A novel method has been developed for the synthesis of alpha-oxycarbanilino
      phosphonates through a reaction of alpha-hydroxyphosphonates with isocyanate
      under microwave irradiation. The synthesized compounds were evaluated for their
      acetylcholinesterase (AChE) inhibition potency through IC(50) determination.
      Molecular modelling studies suggest that the most potent inhibitor (compound 4h,
      IC(50) = 6.36 uM) is bound to the peripheral site of AChE, which suggests that it
      decreases the catalytic activity not through binding to the active site but
      through blocking the entrance of the active site gorge. This puts forward the
      potential of compound 4h and its derivatives to be used in the design of dual
      inhibitors: inhibition of the catalytic activity of AChE and of amyloid beta
      aggregation.

PMID- 22397394
TI  - Synthesis and anticonvulsant activity of 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2
      carboxamide/carbothioamide analogues.
AB  - A series of fourteen 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2
      carboxamide/carbothioamide analogues were synthesized and evaluated for
      anticonvulsant activity according to the Antiepileptic Drug Development Programme
      (ADD) protocol. Some of the synthesized compounds showed significant activity in
      minimal clonic seizure model (6 Hz psychomotor seizure test). 3-(4-Fluorophenyl)
      N-(4-bromophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2
      carboxamide (4c) was found to be the most active compound of the series showing
      75% (3/4, 0.25-2.0 h) and 50% (2/4, 4.0 h) protection against minimal clonic
      seizure at 100 mg/kg without any toxicity. 3-(Pyridin-4-yl)-N-(4-chlorophenyl)
      6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (4f) showed
      protection in maximal electroshock (MES) seizure and subcutaneous metrazol
      (scMET) seizure at 300 mg/kg.

PMID- 22397395
TI  - Synthesis, antimicrobial activity and molecular modeling study of substituted 5
      aryl-pyrimido[5,4-c]quinoline-2,4-diones.
AB  - A series of pyrimido[5,4-c]quinoline-2,4-dione derivatives 5a-k were synthesized
      in moderate yields via a thermolysis reaction of equimolar ratio of 5-arylidine
      1,3-dimethylbarbituric acid derivatives 3a-d with aniline derivatives 4a-d at 150
      180  degrees C for 1-2 h. Eight of the synthesized compounds were chosen for a
      primary in vitro one-dose anticancer assay performed using the full NCI 60 cell
      panel. Only compound 5b showed moderate GI% at the used dose (10 MUM) against
      four of the tested cell lines corresponding to leukemia SR (GI%: 51), non small
      cell lung cancer HOP-92 (GI%: 63), melanoma UACC-62 (GI%: 53) and renal cancer UO
      31 (GI%: 69). On the other hand, antimicrobial screening of the whole set of the
      synthesized compounds was performed against three Gram +ve and two Gram -ve
      bacterial strains. Results of the antimicrobial screening showed that compounds
      5d, 5e, 5f, 5h and 5k have broad-spectrum antibacterial efficacy being moderately
      active against all the tested Gram +ve and two Gram -ve bacteria. Also, compound
      5a showed interesting results being only active against Streptococcus faecalis
      and both tested Gram -ve strains viz. E. coli and P. aeruginosa. In order to
      compare the binding mode of the most active compounds 5e and 5f along with the
      inactive compound 5c we docked these compounds into the empty binding site of
      topoisomerase II DNA gyrase (PDB ID: 1KZN), and results were compared with the
      bound inhibitor Clorobiocin.

PMID- 22397396
TI  - A systematic review of motivational interviewing within musculoskeletal health.
AB  - Motivational interviewing (MI) has been investigated within a range of healthcare
      environments though to date no studies have systematically assessed its
      application and effectiveness within musculoskeletal health. The aim of this
      study is to identify interventions that have utilised MI to create change within
      musculoskeletal healthcare, evaluate quality and effectiveness, as well as
      identify the level of training received by those utilising the approach. The
      search strategy identified both published and unpublished or grey literature
      through electronic resources, reference list and content searches. Five studies
      were identified for quality assessment. Due to variations in delivery modality,
      musculoskeletal condition and type of MI application it was not possible to
      provide direct comparative interpretations for these factors. A data synthesis
      was used to provide a summary of study characteristics, a narrative overview and
      conduct a quality assessment as well as considering authors comments on study
      limitations. The results of the quality assessment highlighted a number of
      methodological issues which supported and expanded upon those expressed by the
      studies authors. None of the studies contained children or young people and in
      terms of training there were variations in training provider, duration and
      competency, as well as variation in the fidelity of MI. The findings have
      highlighted the need for well designed randomised controlled trials that are
      suitability powered to measure the effectiveness of MI within musculoskeletal
      health. Future studies may consider the application of MI within musculoskeletal
      conditions in terms of self-management and its application to creating lifestyle
      changes (e.g., diet, exercise) for adults, as well as children and young people.
      Research currently being conducted may expand upon the evidence, feasibility and
      validity of MI within areas such as fibromyalgia, osteoporosis, arthritis,
      understanding of knee replacement and rehabilitation.

PMID- 22397397
TI  - Measurement of tibial nerve excursion during ankle joint dorsiflexion in a weight
      bearing position with ultrasound imaging.
AB  - BACKGROUND: The ability of peripheral nerves to stretch and slide is thought to
      be of paramount importance to maintain ideal neural function. Excursion in
      peripheral nerves such as the tibial can be measured by analysis of ultrasound
      images. The aim of this study was to assess the degree of longitudinal tibial
      nerve excursion as the ankle moved from plantar flexion to dorsiflexion in a
      standardised weight-bearing position. The reliability of ultrasound imaging to
      measure tibial nerve excursion was also quantified. METHODS: The tibial nerve was
      imaged over two separate sessions in sixteen asymptomatic participants in a
      weight-bearing position. Longitudinal nerve excursion was calculated from a three
      second video loop captured by ultrasound imaging using frame-by-frame cross
      correlation analysis. Intraclass correlation coefficients (ICC) with 95%
      confidence intervals (CI) were used to assess the intra-rater reliability.
      Standard error of the measurement (SEM) and smallest real difference (SRD) were
      calculated to assess measurement error. RESULTS: Mean nerve excursion was 2.99 mm
      SEM +/- 0.22 mm. The SRD was 0.84 mm for session 1 and 0.66 mm for session 2.
      Intra-rater reliability was excellent with an ICC = 0.93. CONCLUSIONS: Assessment
      of real-time ultrasound images of the tibial nerve via frame-by-frame cross
      correlation analysis is a reliable non-invasive technique to assess longitudinal
      nerve excursion. The relationship between foot posture and nerve excursion can be
      further investigated.

PMID- 22397398
TI  - Regulator of calcineurin 1 (Rcan1) has a protective role in brain
      ischemia/reperfusion injury.
AB  - BACKGROUND: An increase in intracellular calcium concentration [Ca2+]i is one of
      the first events to take place after brain ischemia. A key [Ca2+]i-regulated
      signaling molecule is the phosphatase calcineurin (CN), which plays important
      roles in the modulation of inflammatory cascades. Here, we have analyzed the role
      of endogenous regulator of CN 1 (Rcan1) in response to experimental ischemic
      stroke induced by middle cerebral artery occlusion. METHODS: Animals were
      subjected to focal cerebral ischemia with reperfusion. To assess the role of
      Rcan1 after stroke, we measured infarct volume after 48 h of reperfusion in Rcan1
      knockout (KO) and wild-type (WT) mice. In vitro studies were performed in
      astrocyte-enriched cortical primary cultures subjected to 3% oxygen (hypoxia) and
      glucose deprivation (HGD). Adenoviral vectors were used to analyze the effect of
      overexpression of Rcan1-4 protein. Protein expression was examined by
      immunohistochemistry and immunoblotting and expression of mRNA by quantitative
      real-time Reverse-Transcription Polymerase Chain Reaction (real time qRT-PCR).
      RESULTS: Brain ischemia/reperfusion (I/R) injury in vivo increased mRNA and
      protein expression of the calcium-inducible Rcan1 isoform (Rcan1-4). I/R
      inducible expression of Rcan1 protein occurred mainly in astroglial cells, and in
      an in vitro model of ischemia, HGD treatment of primary murine astrocyte cultures
      induced Rcan1-4 mRNA and protein expression. Exogenous Rcan1-4 overexpression
      inhibited production of the inflammatory marker cyclo-oxygenase 2. Mice lacking
      Rcan1 had higher expression of inflammation associated genes, resulting in larger
      infarct volumes. CONCLUSIONS: Our results support a protective role for Rcan1
      during the inflammatory response to stroke, and underline the importance of the
      glial compartment in the inflammatory reaction that takes place after ischemia.
      Improved understanding of non-neuronal mechanisms in ischemic injury promises
      novel approaches to the treatment of acute ischemic stroke.

PMID- 22397399
TI  - The predictive value of microRNA-126 in relation to first line treatment with
      capecitabine and oxaliplatin in patients with metastatic colorectal cancer.
AB  - BACKGROUND: MicroRNA-126 is the only microRNA (miRNA) known to be endothelial
      cell-specific influencing angiogenesis in several ways. The aim of the present
      study was to analyse the possible predictive value of miRNA-126 in relation to
      first line capecitabine and oxaliplatin (XELOX) in patients with metastatic
      colorectal cancer (mCRC). METHODS: The study included 89 patients with mCRC. In
      situ hybridization (ISH) was performed to detect miRNA-126 in formalin-fixed
      paraffin embedded tissue from primary tumours. The expression of miRNA-126, area
      per image (MUm(2)), was measured using image analysis. Clinical response was
      evaluated according to RECIST. Progression free survival (PFS) was compared using
      the Kaplan-Meier method and the log rank test. Tumours were classified as low or
      high miRNA-126 expressing tumours using the median value from the patients with
      response as cut-off. RESULTS: The median miRNA-126 expression level was
      significantly higher in patients responding to XELOX, 3629 MUm(2) (95% CI, 2566
      4846), compared to the patients not responding, 1670 MUm(2) (95% CI, 1436-2041),
      p < 0.0001. The positive predictive value was 90%, and the negative predictive
      value was 71%. The median PFS of patients with high expressing tumours was 11.5
      months (95% CI, 9.0-12.7 months) compared to 6.0 months (95% CI, 4.8-6.9 months)
      for patients with low expressing tumours, p < 0.0001. CONCLUSIONS: Angiogenesis
      quantified by ISH of miRNA-126 was related to response to first line XELOX in
      patients with mCRC, translating to a significant difference in PFS. The
      predictive value of miRNA-126 remains to be further elucidated in prospective
      studies.

PMID- 22397400
TI  - Hyperinsulinemia correlates with low levels of plasma B-type natriuretic peptide
      in Japanese men irrespective of fat distribution.
AB  - BACKGROUND: B-type natriuretic peptide (BNP), a member of the natriuretic peptide
      family, is a cardiac-derived secretory hormone with natriuretic, diuretic, and
      vasorelaxant activities. Intraabdominal fat accumulation is associated with
      atherosclerotic cardiovascular diseases and cardiac dysfunction. Circulating BNP
      levels are relatively low (within the normal limits) in obesity and the metabolic
      syndrome. However, the relationship between plasma BNP levels and visceral fat
      accumulation in general population has not been reported. The present study
      analyzed the relationships between plasma BNP levels and various clinical
      variables, including insulin, visceral and subcutaneous fat area (VFA and SFA,
      respectively), in normal Japanese men. METHODS: The study (Victor-J study)
      subjects were consecutive 500 Japanese male workers, who underwent a health
      checkup and were measured VFA and SFA by computed tomography. RESULTS: Age
      adjusted simple linear regression analysis showed that log-BNP correlated
      positively with HDL-cholesterol, and negatively with VFA, log-immunoreactive
      insulin (IRI), log-triglyceride, and LDL-cholesterol, but not body mass index or
      SFA. Stepwise multiple regression analysis identified log-IRI and HDL-cholesterol
      as significant determinants of log-BNP. Subjects with IRI >=5.5 MUIU/mL had lower
      plasma BNP levels than those with IRI < 5.5 MUIU/mL, irrespective of obesity
      (body mass index, cutoff value 25 kg/m2), visceral fat accumulation (VFA, cutoff
      value 100 cm2) and subcutaneous fat accumulation (SFA, cutoff value 128 cm2).
      CONCLUSIONS: Our study showed that hyperinsulinemia correlated with low levels of
      plasma BNP in general men, irrespective of fat distribution. TRIAL REGISTRATION:
      UMIN 000004318.

PMID- 22397402
TI  - Obtaining enriched compounds via a tandem enantioselective reaction and kinetic
      resolution polishing sequence.
AB  - Herein we describe a tandem method of coupling an enantioselective reaction with
      a nonenzymatic kinetic resolution to prepare highly enantioenriched compounds.
      The procedure employs a moderately selective enantioselective reaction on a
      ketone or aldehyde to form an enriched alcohol followed by a kinetic resolution
      of the alcohol to generate ee's of >99% in yields greater than what is possible
      with a kinetic resolution. This method highlights an avenue to quickly acquire
      highly enriched compounds without developing and optimizing a new methodology.

PMID- 22397401
TI  - Energy landscapes of dynamic ensembles of rolling triplet repeat bulge loops:
      implications for DNA expansion associated with disease states.
AB  - DNA repeat domains can form ensembles of canonical and noncanonical states,
      including stable and metastable DNA secondary structures. Such sequence-induced
      structural diversity creates complex conformational landscapes for DNA processing
      pathways, including those triplet expansion events that accompany replication,
      recombination, and/or repair. Here we demonstrate further levels of
      conformational complexity within repeat domains. Specifically, we show that bulge
      loop structures within an extended repeat domain can form dynamic ensembles
      containing a distribution of loop positions, thereby yielding families of
      positional loop isomers, which we designate as "rollamers". Our fluorescence,
      absorbance, and calorimetric data are consistent with loop
      migration/translocation between sites within the repeat domain
      ("rollamerization"). We demonstrate that such "rollameric" migration of bulge
      loops within repeat sequences can invade and disrupt previously formed base
      paired domains via an isoenthalpic, entropy-driven process. We further
      demonstrate that destabilizing abasic lesions alter the loop distributions so as
      to favor "rollamers" with the lesion positioned at the duplex/loop junction,
      sites where the flexibility of the abasic "universal hinge" relaxes unfavorable
      interactions and/or facilitates topological accommodation. Another strategic
      siting of an abasic site induces directed loop migration toward denaturing
      domains, a phenomenon that merges destabilizing domains. In the aggregate, our
      data reveal that dynamic ensembles within repeat domains profoundly impact the
      overall energetics of such DNA constructs as well as the distribution of states
      by which they denature/renature. These static and dynamic influences within
      triplet repeat domains expand the conformational space available for selection
      and targeting by the DNA processing machinery. We propose that such dynamic
      ensembles and their associated impact on DNA properties influence pathways that
      lead to DNA expansion.

PMID- 22397403
TI  - Contemporary challenges in the design of topoisomerase II inhibitors for cancer
      chemotherapy.

PMID- 22397404
TI  - The NLP toxin family in Phytophthora sojae includes rapidly evolving groups that
      lack necrosis-inducing activity.
AB  - Necrosis- and ethylene-inducing-like proteins (NLP) are widely distributed in
      eukaryotic and prokaryotic plant pathogens and are considered to be important
      virulence factors. We identified, in total, 70 potential Phytophthora sojae NLP
      genes but 37 were designated as pseudogenes. Sequence alignment of the remaining
      33 NLP delineated six groups. Three of these groups include proteins with an
      intact heptapeptide (Gly-His-Arg-His-Asp-Trp-Glu) motif, which is important for
      necrosis-inducing activity, whereas the motif is not conserved in the other
      groups. In total, 19 representative NLP genes were assessed for necrosis-inducing
      activity by heterologous expression in Nicotiana benthamiana. Surprisingly, only
      eight genes triggered cell death. The expression of the NLP genes in P. sojae was
      examined, distinguishing 20 expressed and 13 nonexpressed NLP genes. Real-time
      reverse-transcriptase polymerase chain reaction results indicate that most NLP
      are highly expressed during cyst germination and infection stages. Amino acid
      substitution ratios (Ka/Ks) of 33 NLP sequences from four different P. sojae
      strains resulted in identification of positive selection sites in a distinct NLP
      group. Overall, our study indicates that expansion and pseudogenization of the P.
      sojae NLP family results from an ongoing birth-and-death process, and that
      varying patterns of expression, necrosis-inducing activity, and positive
      selection suggest that NLP have diversified in function.

PMID- 22397405
TI  - A high-throughput virus-induced gene-silencing vector for screening transcription
      factors in virus-induced plant defense response in orchid.
AB  - The large number of species and worldwide spread of species of Orchidaceae
      indicates their successful adaptation to environmental stresses. Thus, orchids
      provide rich resources to study how plants have evolved to cope with stresses.
      This report describes our improvement of our previously reported orchid virus
      induced gene silencing vector, pCymMV-pro60, with a modified Gateway cloning
      system which requires only one recombination and can be inoculated by
      agroinfiltration. We cloned 1,700 DNA fragments, including 187 predicted
      transcription factors derived from an established expression sequence tag library
      of orchid, into pCymMV-Gateway. Phalaenopsis aphrodite was inoculated with these
      vectors that contained DNA fragments of the 187 predicted transcription factors.
      The viral vector initially triggered the expression of the salicylic acid (SA)
      related plant defense responses and later induced silencing of the endogenous
      target transcription factor genes. By monitoring the expression of the SA-related
      plant defense marker PhaPR1 (homolog of PR1), we identified a gene, PhaTF15,
      involved in the expression of PhaPR1. Knockdown of PhaTF15 by virus-induced gene
      silencing and by transient delivery of double-stranded RNA (dsRNA) reduced
      expression of the orchid homolog of the conserved positive defense regulator
      NPR1, PhaNPR1. Cymbidium mosaic virus also accumulated to high levels with
      knockdown of PhaTF15 by transient delivery of dsRNA. We demonstrated efficient
      cloning and screening strategies for high-throughput analysis of orchid and
      identify a gene, PhaTF15, involved in regulation of SA-related plant defense.

PMID- 22397406
TI  - Sinorhizobium fredii HH103 rkp-3 genes are required for K-antigen polysaccharide
      biosynthesis, affect lipopolysaccharide structure and are essential for infection
      of legumes forming determinate nodules.
AB  - The Sinorhizobium fredii HH103 rkp-3 region has been isolated and sequenced.
      Based on the similarities between the S. fredii HH103 rkpL, rkpM, rkpN, rkpO,
      rkpP, and rkpQ genes and their corresponding orthologues in Helicobacter pylori,
      we propose a possible pathway for the biosynthesis of the S. fredii HH103 K
      antigen polysaccharide (KPS) repeating unit. Three rkp-3 genes (rkpM, rkpP, and
      rkpQ) involved in the biosynthesis of the HH103 KPS repeating unit (a derivative
      of the pseudaminic acid) have been mutated and analyzed. All the rkp-3 mutants
      failed to produce KPS and their lipopolysaccharide (LPS) profiles were altered.
      These mutants showed reduced motility and auto-agglutinated when early-stationary
      cultures were further incubated under static conditions. Glycine max, Vigna
      unguiculata (determinate nodule-forming legumes), and Cajanus cajan
      (indeterminate nodules) plants inoculated with mutants in rkpM, rkpQ, or rkpP
      only formed pseudonodules that did not fix nitrogen and were devoid of bacteria.
      In contrast, another indeterminate nodule-forming legume, Glycyrrhiza uralensis,
      was still able to form some nitrogen-fixing nodules with the three S. fredii
      HH103 rifampicin-resistant rkp-3 mutants tested. Our results suggest that the
      severe symbiotic impairment of the S. fredii rkp-3 mutants with soybean, V.
      unguiculata, and C. cajan is mainly due to the LPS alterations rather than to the
      incapacity to produce KPS.

PMID- 22397407
TI  - Evaluation of Arabidopsis thaliana as a model host for Xylella fastidiosa.
AB  - The bacterium Xylella fastidiosa causes a number of plant diseases of significant
      economic impact. To date, progress determining mechanisms of host-plant
      susceptibility, tolerance, or resistance has been slow, due in large part to the
      long generation time and limited available genetic resources for grape, almond,
      and other known hosts of X. fastidiosa. To overcome many of these limitations,
      Arabidopsis thaliana has been evaluated as a host for X. fastidiosa. A pin-prick
      inoculation method has been developed to infect Arabidopsis with X. fastidiosa.
      Following infection, X. fastidiosa multiplies and can be detected by microscopy,
      polymerase chain reaction, and isolation. The ecotypes Van-0, LL-0, and Tsu-1 all
      allow more growth of strain X. fastidiosa Temecula than the reference ecotype Col
      0. Affymetrix ATH1 microarray analysis of inoculated vs. noninoculated Tsu-1
      reveals gene expression changes that differ greatly from changes seen after
      infection with apoplast-colonizing bacteria such as Psuedomonas syringae pvs.
      tomato or syringae. Many genes responsive to oxidative stress are differentially
      regulated, while classic pathogenesis-related genes are not induced by X.
      fastidiosa infection.

PMID- 22397408
TI  - Expression of a single-chain variable-fragment antibody against a Fusarium
      virguliforme toxin peptide enhances tolerance to sudden death syndrome in
      transgenic soybean plants.
AB  - Plants do not produce antibodies. However, plants can correctly assemble
      functional antibody molecules encoded by mammalian antibody genes. Many plant
      diseases are caused by pathogen toxins. One such disease is the soybean sudden
      death syndrome (SDS). SDS is a serious disease caused by the fungal pathogen
      Fusarium virguliforme. The pathogen, however, has never been isolated from
      diseased foliar tissues. Thus, one or more toxins produced by the pathogen have
      been considered to cause foliar SDS. One of these possible toxins, FvTox1, was
      recently identified. We investigated whether expression of anti-FvTox1 single
      chain variable-fragment (scFv) antibody in transgenic soybean can confer
      resistance to foliar SDS. We have created two scFv antibody genes, Anti-FvTox1-1
      and Anti-FvTox1-2, encoding anti-FvTox1 scFv antibodies from RNAs of a hybridoma
      cell line that expresses mouse monoclonal anti-FvTox1 7E8 antibody. Both anti
      FvTox1 scFv antibodies interacted with an antigenic site of FvTox1 that binds to
      mouse monoclonal anti-FvTox1 7E8 antibody. Binding of FvTox1 by the anti-FvTox1
      scFv antibodies, expressed in either Escherichia coli or transgenic soybean
      roots, was initially verified on nitrocellulose membranes. Expression of anti
      FvTox1-1 in stable transgenic soybean plants resulted in enhanced foliar SDS
      resistance compared with that in nontransgenic control plants. Our results
      suggest that i) FvTox1 is an important pathogenicity factor for foliar SDS
      development and ii) expression of scFv antibodies against pathogen toxins could
      be a suitable biotechnology approach for protecting crop plants from toxin
      induced diseases.

PMID- 22397409
TI  - Understanding growers' decisions to manage invasive pathogens at the farm level.
AB  - Globalization causes plant production systems to be increasingly threatened by
      invasive pests and pathogens. Much research is devoted to support management of
      these risks. Yet, the role of growers' perceptions and behavior in risk
      management has remained insufficiently analyzed. This article aims to fill this
      gap by addressing risk management of invasive pathogens from a sociopsychological
      perspective. An analytical framework based on the Theory of Planned Behavior was
      used to explain growers' decisions on voluntary risk management measures. Survey
      information from 303 Dutch horticultural growers was statistically analyzed,
      including regression and cluster analysis. It appeared that growers were
      generally willing to apply risk management measures, and that poor risk
      management was mainly due to perceived barriers, such as high costs and doubts
      regarding efficacy of management measures. The management measures applied varied
      considerably among growers, depending on production sector and farm-specific
      circumstances. Growers' risk perception was found to play a role in their risk
      management, although the causal relation remained unclear. These results
      underscore the need to apply a holistic perspective to farm level management of
      invasive pathogen risk, considering the entire package of management measures and
      accounting for sector- and farm-specific circumstances. Moreover, they
      demonstrate that invasive pathogen risk management can benefit from a
      multidisciplinary approach that incorporates growers' perceptions and behavior.

PMID- 22397410
TI  - Golgi-SNARE GS28 potentiates cisplatin-induced apoptosis by forming GS28-MDM2-p53
      complexes and by preventing the ubiquitination and degradation of p53.
AB  - In the present study, we observed that the Golgi-SNARE (soluble N-ethylmaleimide
      sensitive fusion protein-attachment protein receptor) GS28 forms a complex with
      p53 in HEK (human embryonic kidney)-293 cells. Given that p53 represents a tumour
      suppressor that affects the sensitivity of cancer cells to various
      chemotherapeutic drugs, we examined whether GS28 may influence the level of
      sensitivity to the DNA-damaging drug cisplatin. Indeed, knockdown of GS28 using
      short-hairpin RNA (shGS28) induced resistance to cisplatin in HEK-293 cells. On
      the other hand, overexpression of GS28 sensitized HEK-293 cells to cisplatin,
      whereas no sensitization effect was noted for the mitotic spindle-damaging drugs
      vincristine and taxol. Accordingly, we observed that knockdown of GS28 reduced
      the accumulation of p53 and its pro-apoptotic target Bax. Conversely, GS28
      overexpression induced the accumulation of p53 and Bax as well as the pro
      apoptotic phosphorylation of p53 on Ser(46). Further experiments showed that
      these cellular responses could be abrogated by the p53 inhibitor PFT-alpha
      (pifithrin-alpha), indicating that GS28 may affect the stability and activity of
      p53. The modulatory effects of GS28 on cisplatin sensitivity and p53 stability
      were absent in lung cancer H1299 cells which are p53-null. As expected, ectopic
      expression of p53 in H1299 cells restored the modulatory effects of GS28 on
      sensitivity to cisplatin. In addition, GS28 was found to form a complex with the
      p53 E3 ligase MDM2 (murine double minute 2) in H1299 cells. Furthermore, the
      ubiquitination of p53 was reduced by overexpression of GS28 in cells, confirming
      that GS28 enhances the stability of the p53 protein. Taken together, these
      results suggest that GS28 may potentiate cells to DNA-damage-induced apoptosis by
      inhibiting the ubiquitination and degradation of p53.

PMID- 22397454
TI  - One lumbar extension training session per week is sufficient for strength gains
      and reductions in pain in patients with chronic low back pain ergonomics.
AB  - Chronic low back pain (CLBP) is the leading cause of absenteeism from the
      workplace and research into exercise interventions to address this problem is
      required. This study investigated training frequency for participants with CLBP.
      Participants either trained once a week (1 * week, n = 31), or twice a week (2 *
      week, n = 20) or did not (control group, n = 21). Participants were isometric
      strength tested in weeks 1 and 12 and trained dynamically either 1*week (80% of
      maximum) or 2*week (80% and 50%). The results (pre vs. post) showed significant
      increases in maximal strength, range of motion and reductions in pain for both
      training groups. Pain scores for the 1 * week and 2 * week both reached minimal
      clinical improvement change unlike the control group. Thus, one lumbar extension
      training session per week is sufficient for strength gains and reductions in pain
      in low back pain in CLBP patients. PRACTITIONER SUMMARY: CLBP is the leading
      cause of absenteeism from the workplace. The present study using a modified
      randomised control trial design investigated exercise training frequency for
      participants with CLBP. One lumbar extension training session per week is
      sufficient for strength gains and reductions in low back pain in CLBP patients.

PMID- 22397455
TI  - Visualization and manipulation of individual dopant states in single conjugated
      oligomers.
AB  - Nonlinear excitations associated with dopant states play fundamental roles for
      charge transport in conjugated polymers. Here we report on real-space
      visualization of individual dopant states in single conjugated oligomers of poly
      para-phenylene using cryogenic scanning tunneling microscopy and spectroscopy. We
      have found that these states exhibit a typical spatial extension of 4 nm along
      the oligomers. In particular, these states create a shallow level inside the band
      gap of the parent oligomers. The origin of these states is traced to a novel
      doping mechanism of dehydrogenation of the phenylene moiety. Furthermore, we use
      a scanning tunneling microscope tip to charge/discharge the dopant states and
      measure their lifetimes. The present results demonstrate a strategy to
      characterize and manipulate individual dopant states in conjugated polymers with
      subnanometer resolution.

PMID- 22397453
TI  - Single reporter for targeted multimodal in vivo imaging.
AB  - We have developed a multifaceted, highly specific reporter for multimodal in vivo
      imaging and applied it for detection of brain tumors. A metabolically
      biotinylated, membrane-bound form of Gaussia luciferase was synthesized, termed
      mbGluc-biotin. We engineered glioma cells to express this reporter and showed
      that brain tumor formation can be temporally imaged by bioluminescence following
      systemic administration of coelenterazine. Brain tumors expressing this reporter
      had high sensitivity for detection by magnetic resonance and fluorescence
      tomographic imaging upon injection of streptavidin conjugated to magnetic
      nanoparticles or fluorophore, respectively. Moreover, single photon emission
      computed tomography showed enhanced imaging of these tumors upon injection with
      streptavidin complexed to (111)In-DTPA-biotin. This work shows for the first time
      a single small reporter (~40 kDa) which can be monitored with most available
      molecular imaging modalities and can be extended for single cell imaging using
      intravital microscopy, allowing real-time tracking of any cell expressing it in
      vivo.

PMID- 22397456
TI  - HSPA2 overexpression protects V79 fibroblasts against bortezomib-induced
      apoptosis.
AB  - Human HSPA2 is a member of the HSPA (HSP70) family of heat-shock proteins,
      encoded by the gene originally described as testis-specific. Recently, it has
      been reported that HSPA2 can be also expressed in human somatic tissues in a cell
      type specific manner. The aim of the present study was to find out whether HSPA2
      can increase the resistance of somatic cells to the toxic effect of heat shock,
      proteasome inhibitors, and several anticancer cytostatics. We used a Chinese
      hamster fibroblast V79 cell line because these cells do not express the HSPA2 and
      cytoprotective HSPA1 proteins under normal culture conditions and show limited
      ability to express HSPA1 in response to heat shock and proteasome inhibitors. We
      established, by retroviral gene transfer, a stable V79/HSPA2 cell line, which
      constitutively overexpressed HSPA2 protein. The major observation of our study
      was that HSPA2 increased long-term survival of cells subjected to heat shock and
      proteasome inhibitors. We found, that HSPA2 confers resistance to bortezomib
      induced apoptosis. Thus, we showed for the first time that in somatic cells HSPA2
      can be a part of a system protecting cells against cytotoxic stimuli inducing
      proteotoxic stress.

PMID- 22397457
TI  - delta2H and delta18O of human body water: a GIS model to distinguish residents
      from non-residents in the contiguous USA.
AB  - An understanding of the factors influencing the isotopic composition of body
      water is important to determine the isotopic composition of tissues that are used
      to reconstruct movement patterns of humans. The delta(2)H and delta(18)O values
      of body water (delta(2)H(bw) and delta(18)O(bw)) are related to the delta(2)H and
      delta(18)O values of drinking water (delta(2)H(dw) and delta(18)O(dw)), but
      clearly distinct because of other factors including the composition of food.
      Here, we develop a mechanistic geographical information system (GIS) model to
      produce spatial projections of delta(2)H(bw) and delta(18)O(bw) values for the
      USA. We investigate the influence of gender, food, and drinking water on the
      predicted values by comparing them with the published values. The strongest
      influence on the predicted values was related to the source of delta(2)H(dw) and
      delta(18)O(dw) values. We combine the model with equations that describe the rate
      of turnover to produce estimates for the time required for a non-resident to
      reach an isotopic equilibrium with a resident population.

PMID- 22397458
TI  - Synthesis of selenoxo peptides and oligoselenoxo peptides employing LiAlHSeH.
AB  - Synthesis of selenoxo peptides by the treatment of N(alpha)-protected peptide
      esters with a combination of PCl(5) and LiAlHSeH is delineated. The method is
      simple, high-yielding, and free from racemization. Thus obtained selenoxo
      peptides are used as units for N-terminal chain extension through N(alpha)
      deprotection/coupling to yield peptide-selenoxo peptide hybrids. Multiple
      selenation is demonstrated by conversion of two peptide bonds of tripeptides into
      selenoxo peptide bonds. Amino acid derived arylamides are also converted into
      aryl selenoamides. C(6)H(5)-CSeNH-Val-OMe 8f is obtained as single  crystal, and
      its structure was determined through X-ray diffraction study.

PMID- 22397459
TI  - Genetic and non-genetic factors affecting the response to clopidogrel therapy.
AB  - INTRODUCTION: Clopidogrel (CLP) is a second-generation thienopyridine that
      prevents platelet aggregation by inhibiting the adenosine diphosphate receptor
      located on the platelet surface. The use of CLP in combination with aspirin has
      become standard treatment in patients with acute coronary syndromes and stent
      implantation. Data suggests that a significant percentage of individuals treated
      with CLP do not receive the expected therapeutic benefit because of a decreased
      platelet inhibition. The clinical consequences of an inadequate platelet response
      are cardiovascular complications, which can lead to acute myocardial infarction,
      stroke and death. The mechanism underlying CLP resistance is multifactorial and
      includes genetic polymorphisms and non-genetic causes (such as drug-drug
      interactions, co-morbidities, age). AREAS COVERED: This article reviews the so
      far accumulated evidence on the role of genetic polymorphisms and non-genetic
      factors, as determinants of the antiplatelet response to CLP. Pharmacodynamic and
      clinical aspects of the CLP nonresponsiveness are also presented. Relevant papers
      were identified by an extensive PubMed search using appropriate keywords. EXPERT
      OPINION: Impaired platelet inhibition in CLP poor responders is a real problem,
      as it leads to serious clinical consequences. Therefore, prediction models that
      include pharmacogenetic knowledge and non-genetic risk factors of low response to
      the drug are needed in the individualization of antithrombotic therapy.
      Alternative antiplatelet strategies that should be considered to overcome this
      problem include dose modification, adjunctive antiplatelet drug usage, and use of
      newer agents.

PMID- 22397460
TI  - Field validation of polyethylene passive air samplers for parent and alkylated
      PAHs in Alexandria, Egypt.
AB  - Polyethylene samplers (PEs) were deployed at 11 locations in Alexandria, Egypt
      during summer and winter to test and characterize them as passive samplers for
      concentrations, sources, and seasonal variations of atmospheric concentrations of
      polycyclic aromatic hydrocarbons (PAHs). PE-air equilibrium was attained faster
      for a wider range of PAHs during the winter season possibly due to increased wind
      speeds. Calculated PE-air partitioning constants, K(PE-A), in our study [Log K(PE
      A) = 0.9426 * Log K(OA) - 0.022 (n = 12, R(2) = 0.99, Std error = 0.053)] agreed
      with literature values within <46%. For parent (except naphthalene), mono- and
      dialkylated PAHs, active sampling based concentrations of PAHs were within an
      average factor of 1.4 (1.0-5.6) compared to the PE based values. For C(3-4)
      alkylated PAHs, K(PE-A) values were lower than predicted, on average by ~0.8 log
      units per carbon in the alkylation. Enthalpies of vaporization (DeltaH(vap))
      accurately corrected K(PE-A)s for temperature differences between winter and
      summer sampling. PAH profiles were dominated by naphthalene, phenanthrene, and
      alkylated phenanthrenes. Calculated diagnostic ratios indicated that PAHs
      originated mainly from vehicle emissions.

PMID- 22397462
TI  - Contextualizing chronicity: a perspective from Malaysia.

PMID- 22397463
TI  - Willingness to seek malaria treatment among Togolese people.
AB  - The way Togolese people judge their willingness to seek malaria treatment in
      health facilities as a function of a set of concrete circumstances was examined.
      Three hundred and thirty-one people in Lome, Togo, were presented with 32
      scenarios of a few lines depicting a situation of illness strongly suggestive of
      malaria, and were instructed to judge their willingness to consult in each case.
      The scenarios were developed according to a five within-subject factor design:
      (1) severity of symptoms, (2) cost of treatment, (3) caregivers' attitudes, (4)
      availability of traditional treatment and (5) family's attitude with regards to
      use of formal health services. All these factors had significant effects. The
      severity factor had the strongest effect, and attitude of the family had the
      weakest effect. The other three factors had more or less the same impact.
      Implications for health policy are discussed.

PMID- 22397461
TI  - Dynamics of subcellular proteomes during brain development.
AB  - Many neurological disorders are caused by perturbations during brain development,
      but these perturbations cannot be readily identified until there is comprehensive
      description of the development process. In this study, we performed mass
      spectrometry analysis of the synaptosomal and mitochondrial fractions from three
      rat brain regions at four postnatal time points. To quantitate our analysis, we
      employed (15)N labeled rat brains using a technique called SILAM (stable isotope
      labeling in mammals). We quantified 167429 peptides and identified over 5000
      statistically significant changes during development including known disease
      associated proteins. Global analysis revealed distinct trends between the
      synaptic and nonsynaptic mitochondrial proteomes and common protein networks
      between regions each consisting of a unique array of expression patterns.
      Finally, we identified novel regulators of neurodevelopment that possess the
      identical temporal pattern of known regulators of neurodevelopment. Overall, this
      study is the most comprehensive quantitative analysis of the developing brain
      proteome to date, providing an important resource for neurobiologists.

PMID- 22397464
TI  - Mild hypothermia of 34 degrees C reduces side effects of rt-PA treatment after
      thromboembolic stroke in rats.
AB  - BACKGROUND: Hypothermia is neuroprotective in experimental stroke and may extend
      the so far limited therapeutic time window for thrombolysis. Therefore,
      hypothermia of 34 degrees C and its effects on delayed thrombolysis including
      reperfusion-associated injury were investigated in a model of thromboembolic
      stroke (TE). METHODS: Male Wistar rats (n = 48) were subjected to TE. The
      following treatment groups were investigated: control group - normothermia (37
      degrees C); thrombolysis group - rt-PA 90 min after TE; hypothermia by 34 degrees
      C applied 1.5 to 5 hours after TE; combination therapy- hypothermia and rt-PA.
      After 24 hours infarct size, brain edema and neuroscore were assessed. Protein
      markers for inflammation and adhesion, gelatinase activity, and blood brain
      barrier (BBB) disruption were determined. MRI-measurements investigated infarct
      evolution and blood flow parameters. RESULTS: The infarct volume and brain
      swelling were smaller in the hypothermia group compared to the other groups (p <
      0.05 to p < 0.01). Thrombolysis resulted in larger infarct and brain swelling
      than all others. Hypothermia in combination with thrombolysis reduced these
      parameters compared to thrombolysis (p < 0.05). Moreover, the neuroscore improved
      in the hypothermia group compared to control and thrombolysis. Animals of the
      combination therapy performed better than after thrombolysis alone (p < 0.05).
      Lower serum concentration of sICAM-1, and TIMP-1 were shown for hypothermia and
      combination therapy. Gelatinase activity was decreased by hypothermia in both
      groups. CONCLUSIONS: Therapeutic hypothermia reduced side-effects of rt-PA
      associated treatment and reperfusion in our model of TE.

PMID- 22397466
TI  - Probing the ATP hydrolysis cycle of the ABC multidrug transporter LmrA by pulsed
      EPR spectroscopy.
AB  - Members of the ATP binding cassette (ABC) transporter superfamily translocate
      various types of molecules across the membrane at the expense of ATP. This
      requires cycling through a number of catalytic states. Here, we report
      conformational changes throughout the catalytic cycle of LmrA, a homodimeric
      multidrug ABC transporter from L. lactis. Using site-directed spin labeling and
      pulsed electron-electron double resonance (PELDOR/DEER) spectroscopy, we have
      probed the reorientation of the nucleotide binding domains and transmembrane
      helix 6 which is of particular relevance to drug binding and part of the
      dimerization interface. Our data show that LmrA samples a very large
      conformational space in its apo state, which is significantly reduced upon
      nucleotide binding. ATP binding but not hydrolysis is required to trigger this
      conformational change, which results in a relatively fixed orientation of both
      the nucleotide binding domains and transmembrane helices 6. This orientation is
      maintained throughout the ATP hydrolysis cycle until the protein cycles back to
      its apo state. Our data present strong evidence that switching between two
      dynamically and structurally distinct states is required for substrate
      translocation.

PMID- 22397465
TI  - Effect of indoor air pollution from biomass and solid fuel combustion on
      prevalence of self-reported asthma among adult men and women in India: findings
      from a nationwide large-scale cross-sectional survey.
AB  - OBJECTIVES: Increasing prevalence of asthma in developing countries has been a
      significant challenge for public health in recent decades. A number of studies
      have suggested that ambient air pollution can trigger asthma attacks. Biomass and
      solid fuels are a major source of indoor air pollution, but in developing
      countries the health effects of indoor air pollution are poorly understood. In
      this study we examined the effect of cooking smoke produced by biomass and solid
      fuel combustion on the reported prevalence of asthma among adult men and women in
      India. METHODS: The analysis is based on 99,574 women and 56,742 men aged between
      20 and 49 years included in India's third National Family Health Survey conducted
      in 2005-2006. Effects of exposure to cooking smoke, determined by the type of
      fuel used for cooking such as biomass and solid fuels versus cleaner fuels, on
      the reported prevalence of asthma were estimated using multivariate logistic
      regression. Since the effects of cooking smoke are likely to be confounded with
      effects of tobacco smoking, age, and other such factors, the analysis was carried
      out after statistically controlling for such factors. RESULTS: The results
      indicate that adult women living in households using biomass and solid fuels have
      a significantly higher risk of asthma than those living in households using
      cleaner fuels (OR: 1.26; 95%CI: 1.06-1.49; p = .010), even after controlling for
      the effects of a number of potentially confounding factors. Interestingly, this
      effect was not found among men (OR: 0.98; 95%CI: 0.77-1.24; p = .846). However,
      tobacco smoking was associated with higher asthma prevalence among both women
      (OR: 1.72; 95%CI: 1.34-2.21; p < .0001) and men (OR: 1.35; 95%CI: 1.49-2.25; p <
      .0001). Combined effects of biomass and solid fuel use and tobacco smoke on the
      risk of asthma were greater and more significant in women (OR: 2.16; 95%CI: 1.58
      2.94; p < .0001) than they were in men (OR: 1.34; 95%CI: 1.04-1.72; p = .024).
      CONCLUSIONS: The findings have important program and policy implications for
      countries such as India, where large proportions of the population still rely on
      polluting biomass fuels for cooking and heating. Decreasing household biomass and
      solid fuel use and increasing use of improved stove technology may decrease the
      health effects of indoor air pollution. More epidemiological research with better
      measures of smoke exposure and clinical measures of asthma is needed to validate
      the findings.

PMID- 22397467
TI  - Characterization and antioxidant potential of Brazilian fruits from the Myrtaceae
      family.
AB  - The objective of this study is to evaluating the Brazilian biodiversity through
      physicochemical characterization and determination of antioxidant potential of
      three species from the Myrtaceae family, namely yellow guava (Psidium cattleyanum
      Sabine), guabiroba (Campomanesia xanthocarpa O. Berg), and uvaia ( Eugenia
      pyriformis Cambess). Guabiroba had the greater quantity of phenolic compounds
      (9033 mg chlorogenic acid/100 g) and vitamin C (30.58 mg/g) and showed the best
      TSS/TTA (total soluble solid/total titratable acid) ratio (45.12). For the ABTS
      (2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic) method, the guabiroba (507.49
      MUM Trolox/g) presented the highest antioxidant potential; however, in the DPPH
      (2,2-diphenyl-1-picrylhydrazyl) method, uvaia (170.26 g/g DPPH) and guabiroba
      (161.29 g/g DPPH) were not statistically different. The uvaia outranked the other
      fruits with respect to its high carotenoid (909.33 MUg/g) and vitamin A (37.83
      MUg/g) contents, and the yellow guava, although showing a lower bioactive
      compound content and antioxidant activity, nevertheless presented much higher
      values than many traditionally consumed fruits.

PMID- 22397468
TI  - Community based needs assessment in an urban area: a participatory action
      research project.
AB  - BACKGROUND: Community assessment is a core function of public health. In such
      assessments, a commitment to community participation and empowerment is at the
      heart of the WHO European Healthy Cities Network, reflecting its origins in
      health for all and the Ottawa Charter for Health Promotion. This study employs a
      participation and empowerment plan in order to conduct community assessment.
      METHODS: The method of participatory action research (PAR) was used. The study
      was carried out in an area of high socio-economic deprivation in Ardabil, a city
      in the northwest of Iran, which is currently served by a branch of the Social
      Development Center (SDC). The steering committee of the project was formed by
      some university faculty members, health officials and delegates form Farhikhteh
      non-governmental organization and representatives from twelve blocks or districts
      of the community. Then, the representatives were trained and then conducted focus
      groups in their block. The focus group findings informed the development of the
      questionnaire. About six hundred households were surveyed and study
      questionnaires were completed either during face-to-face interviews by the
      research team (in case of illiteracy) or via self-completion. The primary
      question for the residents was: 'what is the most important health problem in
      your community? Each health problem identified by the community was weighted
      based on the frequency it was selected on the survey, and steering committee
      perception of the problem's seriousness, urgency, solvability, and financial
      load. RESULTS: The main problems of the area appeared to be the asphalt problem,
      lack of easy access to medical centers, addiction among relatives and
      unemployment of youth. High participation rates of community members in the
      steering committee and survey suggest that the PAR approach was greatly
      appreciated by the community and that problems identified through this research
      truly reflect community opinion. CONCLUSIONS: Participatory action research is an
      effective method for community assessments. However, researchers must rigorously
      embrace principles of mutual cooperation, respect for public ideas, and a robust
      belief in community empowerment in order to pave the way for responsible and
      active citizen participation in the various stages of research.

PMID- 22397469
TI  - Urinary corticosteroid excretion predicts left ventricular mass and proteinuria
      in chronic kidney disease.
AB  - Blockade of the MR (mineralocorticoid receptor) in CKD (chronic kidney disease)
      reduces LVMI [LV (left ventricular) mass index] and proteinuria. The MR can be
      activated by aldosterone, cortisol and DOC (deoxycorticosterone). The aim of the
      present study was to explore the influence of mineralocorticoids on LVMI and
      proteinuria in patients with CKD. A total of 70 patients with CKD and 30 patients
      with EH (essential hypertension) were recruited. Patients underwent clinical
      phenotyping; biochemical assessment and 24 h urinary collection for THAldo
      (tetrahydroaldosterone), THDOC (tetrahydrodeoxycorticosterone), cortisol
      metabolites (measured using GC-MS), and urinary electrolytes and protein [QP
      (proteinuira quantification)]. LVMI was measured using CMRI (cardiac magnetic
      resonance imaging). Factors that correlated significantly with LVMI and
      proteinuria were entered into linear regression models. In patients with CKD,
      significant predictors of LVMI were male gender, SBP (systolic blood pressure),
      QP, and THAldo and THDOC excretion. Significant independent predictors on
      multivariate analysis were THDOC excretion, SBP and male gender. In EH, no
      association was seen between THAldo or THDOC and LVMI; plasma aldosterone
      concentration was the only significant independent predictor. Significant
      univariate determinants of proteinuria in patients with CKD were THAldo, THDOC,
      USod (urinary sodium) and SBP. Only THAldo excretion and SBP were significant
      multivariate determinants. Using CMRI to determine LVMI we have demonstrated that
      THDOC is a novel independent predictor of LVMI in patients with CKD, differing
      from patients with EH. Twenty-four hour THAldo excretion is an independent
      determinant of proteinuria in patients with CKD. These findings emphasize the
      importance of MR activation in the pathogenesis of the adverse clinical phenotype
      in CKD.

PMID- 22397471
TI  - Temporal and spatial profiling of internode elongation-associated protein
      expression in rapidly growing culms of bamboo.
AB  - In natural conditions, culms of developing Moso bamboo, Phyllostachys heterocycla
      var. pubescens, reach their final height of more than ten meters within a short
      period of two to four months. To study this phenomenon, bamboo culm material
      collected from different developmental stages and internodes was analyzed.
      Histological observations indicated that the development of culm was dominated by
      cell division in the initial stages and by cell elongation in the middle and late
      stages. Development, maturation, and aging in different regions of the culm were
      studied systematically from the basal to the top internode. The four major
      endogenous hormones, indole acetic acid, gibberellic acid, zeatin riboside, and
      abscisic acid appeared to strongly influence the cell elongation phase. A total
      of 258 spots were differentially expressed in culm development. Of these, 213
      spots were identified by MALDI-TOF/TOF MS and were involved in many physiological
      and metabolic processes including carbohydrate metabolism, cell division, cell
      expansion, protein synthesis, amino acid metabolism and redox homeostasis. These
      proteins with different expression patterns constructed an ingenious network to
      regulate the culm development. Developmental stage-specific and internode
      specific protein expression patterns were identified. Protein abundance was
      regulated temporally and to some extent spatially, and the sequential development
      from base to apex of bamboo culm was implemented by temporal and spatial
      expression of enzymes. Results indicate that during development energy was mainly
      derived from sucrose degradation, as photosynthetic capacity was poor. The
      regulation of anaerobic and aerobic modes of respiration appeared to play an
      important role in energy generation. This is the first report on proteomic
      profiling in bamboo and helps in understanding the regulatory processes in
      developing culms.

PMID- 22397470
TI  - Preliminary clinical study of left ventricular myocardial strain in patients with
      non-ischemic dilated cardiomyopathy by three-dimensional speckle tracking
      imaging.
AB  - BACKGROUND: Non-ischemic dilated cardiomyopathy (DCM) is the most common
      cardiomyopathy worldwide, with significant mortality. Correct evaluation of the
      patient's myocardial function has important clinical significance in the
      diagnosis, therapeutic effect assessment and prognosis in non-ischemic DCM
      patients. This study evaluated the feasibility of three-dimensional speckle
      tracking imaging (3D-STE) for assessment of the left ventricular myocardial
      strain in patients with non-ischemic dilated cardiomyopathy (DCM). METHODS:
      Apical full-volume images were acquired from 65 patients with non-ischemic DCM
      (DCM group) and 59 age-matched normal controls (NC group), respectively. The
      following parameters were measured by 3D-STE: the peak systolic radial strain
      (RS), circumferential strain (CS), longitudinal strain (LS) of each segment. Then
      all the parameters were compared between the two groups. RESULTS: The peak
      systolic strain in different planes had certain regularities in normal groups,
      radial strain (RS) was the largest in the mid region, the smallest in the apical
      region, while circumferential strain (CS) and longitudinal strain (LS) increased
      from the basal to the apical region. In contrast, the regularity could not be
      applied to the DCM group. RS, CS, LS were significantly decreased in DCM group as
      compared with NC group (P < 0.001 for all). The interobserver, intraobserver and
      test-retest reliability were acceptable. CONCLUSIONS: 3D-STE is a reliable tool
      for evaluation of left ventricular myocardial strain in patients with non
      ischemic DCM, with huge advantage in clinical application.

PMID- 22397472
TI  - Attitudes towards credit and finances among college students in China and the
      United States.
AB  - Although there is growing concern about the issue of credit card debt among
      college students in China, little research has examined attitudes to money and
      debt among that group. The present study compared financial self-confidence,
      perceived financial wellbeing, attitudes to debt, and parent education about
      money and debt in 410 college students from the US and China. Although college
      students in China reported fewer credit cards and less debt, they also reported
      lower levels of financial self-confidence and financial wellbeing. In both
      cultures, delay of gratification and parental education predicted both self
      confidence and financial wellbeing. 

PMID- 22397475
TI  - The IMI awards.

PMID- 22397476
TI  - The role of photography in dermatology research.
AB  - This article discusses the role of clinical photography in dermatology research
      and the value of healthcare professionals engaging with clinical photographers
      when planning and undertaking clinical photography. It is not always feasible to
      use a clinical photographer, or clinicians may not have access to such a service,
      but with advice, support and training from clinical photographers, clinicians can
      take good clinical photographs with easy-to-use low cost equipment. This article
      provides an exemplar where good quality clinical photographs have been obtained
      of congenital erythropoietic porphyria (CEP) patients for dermatology research.
      The images have been taken by a dermatologist, with guidance from trained
      clinical photographers. The photographs played a valuable role in providing a
      visual, comparative and comprehensive description of this extremely rare multi
      system disease.

PMID- 22397478
TI  - Gallery.

PMID- 22397479
TI  - Colour management benefits from the image skin tone optimisation and verification
      (ISTOV) system.

PMID- 22397480
TI  - A camera support for operating theatre videography.
AB  - We describe the design, construction and evaluation of a custom-made camera
      support to gain better access for recording videos of open surgery.

PMID- 22397481
TI  - Using flashcards to support your learning.
AB  - The idea that if you listen to a lecture and make notes you will, by some
      mysterious process, have learnt all that the lecturer has covered, is a myth.
      Unfortunately, the lecture is just the start. The best way to learn is by doing.
      This can be achieved by completing set practical tasks by reading and creating
      your own notes, listening again to parts or the whole of a lecture via a
      screencast or using diagrams and illustrations that you annotate. Similarly
      creating your own learning materials can be useful as actually putting questions
      and answers together helps you to learn.   One of the many ways to support your
      learning, especially in difficult topics like anatomy and physiology, learning
      about bones, medical terminology or indeed any subject where there are a lot of
      new words and terms to learn, is making use of an old technique brought up to
      date with new technologies called "flashcards".

PMID- 22397485
TI  - '3Dme--a look inside' creative studio.
AB  - 3Dme are creative 3D digital story-tellers with a passion for making complex
      health and medical information comprehensible. They have an enviable ability to
      understand a broad range of health and medical topics and present them in an
      accurate and visually engaging manner. '3Dme - A Look Inside' is a privately
      owned 3D visualisation and multimedia company established by Luke and Sonya
      Brannelly in 2006. 3Dme are passionate about creating beautiful, scientifically
      accurate, relevant, high definition, full 3D visualisation presentations to take
      a look inside the human body to communicate a health or medical education message
      via engaging, creative digital story-telling. 3Dme's primary objective is to
      'improve global health and education outcomes'. Winning a number of local and
      international awards for their work, they are well on their way to achieving
      this. 3Dme's vision is simply to use their scientific and artistic skills along
      with the reach of the internet and digital technology, to captivate, engage and
      inspire everyone from primary school students, teachers and parents, through to
      university undergraduates, academics and medical specialists, to improve their
      understanding of complex health and medical topics. The digital output of their
      3D presentations is suitable for a variety of delivery platforms and includes e
      learning modules, blended learning, interactive learning modules and Apps. 3Dme
      has made, and continues to make, significant investments in technology based
      hardware and software, boasting one of the largest in-house, fully equipped
      animation render farms in Queensland, Australia.

PMID- 22397486
TI  - In situ electrokinetic enhancement for self-assembled-monolayer-based
      electrochemical biosensing.
AB  - This study reports a multifunctional electrode approach which directly implements
      electrokinetic enhancement on a self-assembled-monolayer-based electrochemical
      sensor for point-of-care diagnostics. Using urinary tract infections as a model
      system, we demonstrate that electrokinetic enhancement, which involves in situ
      stirring and heating, can enhance the sensitivity of the strain specific 16S rRNA
      hybridization assay for 1 order of magnitude and accelerate the time-limiting
      incubation step with a 6-fold reduction in the incubation time. Since the same
      electrode platform is used for both electrochemical signal enhancement and
      electrochemical sensing, the multifunctional electrode approach provides a highly
      effective strategy toward fully integrated lab-on-a-chip systems for various
      biomedical applications.

PMID- 22397489
TI  - Open-loop and feedback-controlled mouse cursor movements in linear paths.
AB  - Path length (A), path width (W) and movement direction (theta) are identified as
      the main factors affecting visually-controlled movement times in linear paths.
      Effects of A and W are well described by Drury's ( 1971 . Movements with lateral
      constraint. Ergonomics, l4 (2), 293-305.) model in which movement time is
      linearly related to the ratio of A/W. At low A/W values, departure from linearity
      has been identified but not investigated in detail. Data are presented for both
      open-loop and feedback-controlled movements in linear paths at 0, 60 and 150
      degrees  movement directions. Movement amplitude and path width were varied over
      a wide range to determine the effects of A and (A/W) on movement time. Movements
      were found to be made ballistically or in open-loop mode when the ratio (A/W) was
      less than about 8 to 10 and the movement times were linearly related to ?A for
      all angles of movement. Feedback-controlled movements followed Drury's law;
      ballistic movements had movement speed linear with ?A. PRACTITIONER SUMMARY: Many
      tasks require manoeuvring equipment or devices through a path of limited width.
      These movements can be made with or without feedback control, depending on the
      path constraints. The conditions for the two forms of movement are determined in
      this research.

PMID- 22397488
TI  - Cardiac biomarkers in the intensive care unit.
AB  - Cardiac biomarkers (CB) were first developed for assisting the diagnosis of
      cardiac events, especially acute myocardial infarction. The discoveries of other
      CB, the better understanding of cardiac disease process and the advancement in
      detection technology has pushed the applications of CB beyond the 'diagnosis'
      boundary. Not only the measurements of CB are more sensitive, the applications
      have now covered staging of cardiac disease, timing of cardiac events and
      prognostication. Further, CB have made their way to the intensive care setting
      where their uses are not just confined to cardiac related areas. With the better
      understanding of the CB properties, CB can now help detecting various acute
      processes such as pulmonary embolism, sepsis-related myocardial depression, acute
      heart failure, renal failure and acute lung injury. This article discusses the
      properties and the uses of common CB, with special reference to the intensive
      care setting. The potential utility of "multimarkers" approach and microRNA as
      the future CB are also briefly discussed.

PMID- 22397490
TI  - Disaster waste characteristics and radiation distribution as a result of the
      Great East Japan Earthquake.
AB  - The compounded impacts of the catastrophes that resulted from the Great East
      Japan Earthquake have emphasized the need to develop strategies to respond to
      multiple types and sources of contamination. In Japan, earthquake and tsunami
      generated waste were found to have elevated levels of metals/metalloids (e.g.,
      mercury, arsenic, and lead) with separation and sorting more difficult for
      tsunami-generated waste as opposed to earthquake-generated waste. Radiation
      contamination superimposed on these disaster wastes has made it particularly
      difficult to manage the ultimate disposal resulting in delays in waste
      management. Work is needed to develop policies a priori for handling wastes from
      combined catastrophes such as those recently observed in Japan.

PMID- 22397491
TI  - Site energies of active and inactive pheophytins in the reaction center of
      Photosystem II from Chlamydomonas reinhardtii.
AB  - It is widely accepted that the primary electron acceptor in various Photosystem
      II (PSII) reaction center (RC) preparations is pheophytin a (Pheo a) within the
      D1 protein (Pheo(D1)), while Pheo(D2) (within the D2 protein) is photochemically
      inactive. The Pheo site energies, however, have remained elusive, due to inherent
      spectral congestion. While most researchers over the past two decades placed the
      Q(y)-states of Pheo(D1) and Pheo(D2) bands near 678-684 and 668-672 nm,
      respectively, recent modeling [Raszewski et al. Biophys. J. 2005, 88, 986 - 998;
      Cox et al. J. Phys. Chem. B 2009, 113, 12364 - 12374] of the electronic structure
      of the PSII RC reversed the assignment of the active and inactive Pheos,
      suggesting that the mean site energy of Pheo(D1) is near 672 nm, whereas Pheo(D2)
      (~677.5 nm) and Chl(D1) (~680 nm) have the lowest energies (i.e., the Pheo(D2)
      dominated exciton is the lowest excited state). In contrast, chemical pigment
      exchange experiments on isolated RCs suggested that both pheophytins have their
      Q(y) absorption maxima at 676-680 nm [Germano et al. Biochemistry 2001, 40, 11472
      - 11482; Germano et al. Biophys. J. 2004, 86, 1664 - 1672]. To provide more
      insight into the site energies of both Pheo(D1) and Pheo(D2) (including the
      corresponding Q(x) transitions, which are often claimed to be degenerate at 543
      nm) and to attest that the above two assignments are most likely incorrect, we
      studied a large number of isolated RC preparations from spinach and wild-type
      Chlamydomonas reinhardtii (at different levels of intactness) as well as the
      Chlamydomonas reinhardtii mutant (D2-L209H), in which the active branch Pheo(D1)
      is genetically replaced with chlorophyll a (Chl a). We show that the Q(x)-/Q(y)
      region site energies of Pheo(D1) and Pheo(D2) are ~545/680 nm and ~541.5/670 nm,
      respectively, in good agreement with our previous assignment [Jankowiak et al. J.
      Phys. Chem. B 2002, 106, 8803 - 8814]. The latter values should be used to model
      excitonic structure and excitation energy transfer dynamics of the PSII RCs.

PMID- 22397493
TI  - Current and future pharmacological treatment strategies with regard to aortic
      disease in Marfan syndrome.
AB  - INTRODUCTION: Marfan syndrome is a multisystemic connective tissue disorder
      caused mainly by mutations in the fibrillin-1 gene. The entire cardiovascular
      system is affected in patients with Marfan syndrome. Aortic root dilatation,
      aortic valve regurgitation or - the most feared and life-threatening symptom -
      aortic root dissection are the most common manifestations. Therapeutic
      strategies, such as prophylactic aortic root surgery and pharmacological therapy,
      focus on the prevention of aortic dissection. Currently, the standard medicinal
      treatments targeting aortic dilatation and dissection consist of agents generally
      used to lower blood pressure and/or the inotropic state of the heart. By these
      means, the cyclic repetitive forces exerted on the aortic wall are diminished and
      thus the onset of aortic dilatation is potentially prevented. Although these
      pharmacological agents may offer some benefit in reduction of aortic aneurysm
      expansion rate, they do not target the underlying cause of the progressive aortic
      degradation. AREAS COVERED: This review discusses the effectiveness of frequently
      prescribed medications used to prevent and delay aortic complications in Marfan
      syndrome. New insights on the biochemical pathways leading to aortic disease are
      also discussed to highlight new targets for pharmacological therapy. EXPERT
      OPINION: Recent insights in the transforming growth factor beta signaling pathway
      and inflammatory mechanisms in a well-established mouse model of Marfan syndrome,
      have led to studies exploring new pharmacological treatment strategies with
      doxycycline, statins and angiotensin II receptor blockers. Pharmacological
      therapy is focused more on prevention than on delay of aortic wall pathology in
      Marfan syndrome. Of the new pharmacological treatment strategies targeting aortic
      pathology in Marfan syndrome, angiotensin receptor type 1 blockers are promising
      candidates, with several clinical trials currently ongoing.

PMID- 22397492
TI  - Dolphin Morbillivirus and Toxoplasma gondii coinfection in a Mediterranean fin
      whale (Balaenoptera physalus).
AB  - BACKGROUND: Although Morbillivirus and Toxoplasma gondii have emerged as
      important pathogens for several cetaceans populations over the last 20 years,
      they have never been identified together in a Mysticete. In particular,
      morbilliviral infection has been never described in the Mediterranean fin whale
      population. CASE PRESENTATION: On January 2011 an adult male of fin whale
      (Balaenoptera physalus) stranded along the Tyrrhenian coastline of Italy. During
      necropsy, tissue samples from heart, skeletal muscle, mesenteric lymph nodes,
      liver, spleen, lung, and kidney were collected and subsequently analyzed for
      Morbillivirus and Toxoplasma gondii by microscopic and molecular methods.
      Following the detailed necropsy carried out on this whale, molecular analysis
      revealed, for the first time, the simultaneous presence of a Dolphin
      Morbillivirus (DMV) and T. gondii infection coexisting with each other, along
      with high organochlorine pollutant concentrations, with special reference to DDT.
      CONCLUSION: This report, besides confirming the possibility for Mysticetes to be
      infected with DMV, highlights the risk of toxoplasmosis in sea water for mammals,
      already immunodepressed by concurrent factors as infections and environmental
      contaminants.

PMID- 22397494
TI  - The role of positive thinking in social perceptions of cancer outcomes.
AB  - Pressure for 'positive thinking' (PT; i.e., focusing on positive
      thoughts/suppressing negative thoughts to 'fight' cancer) burdens cancer patients
      facing health deterioration. It was determined whether PT exposure enhanced
      effort, control and responsibility attributions assigned to an individual for
      his/her cancer trajectory. Within an online blog a hypothetical same-gender
      person describes a personal cancer experience. 482 participants were assigned to
      one of six experimental conditions in which we manipulated PT exposure (blogger
      learns about 'power of PT' but does not try it, blogger tries PT, control/no PT)
      and cancer outcome (successful/unsuccessful treatment). A 3 * 2 * 2 multivariate
      analysis of covariance (with personal cancer experience covariates) tested PT
      exposure * cancer outcome * gender effects on attributions for the blogger's
      cancer outcome. Results indicate that PT exposure enhanced effort and
      responsibility attributions assigned to individuals for their cancer outcomes and
      that responsibility attributions differed as a function of gender. Findings
      suggest that exposure to the idea of PT may lead to cancer patients being
      perceived as culpable if they do not recover from the disease.

PMID- 22397495
TI  - Effect of bovine lactoferrin on the minimum inhibitory concentrations of
      ampicillin and trimethoprim-sulfamethoxazole for clinical Shigella spp. strains.
AB  - Here, we determined the effect of bovine lactoferrin (bLF) on the minimum
      inhibitory concentration (MIC) of ampicillin and trimethoprim-sulfamethoxazole in
      Shigella . Using a microdilution method, the MIC was determined in the presence
      or absence of bovine lactoferrin (10 mg/mL) on 88 Shigella strains (56 Shigella
      flexneri , 15 Shigella boydii , 13 Shigella sonnei , and 4 Shigella dysenteriae )
      previously isolated from peruvian children <2 years old. A fold change of 2 or
      more in MIC values was considered significant. For ampicillin, 67 (76%) strains
      were highly resistant; one-third of the strains (32%) showed a decrease in
      ampicillin MIC in the presence of LF. This was more typical of MIC values in less
      resistant strains. For 7 (8%) ampicillin-resistant strains, the decrease in the
      MIC resulted in the strains reaching the cutoff for susceptible in the presence
      of bLF. For trimethoprim-sulfamethoxazole, 93% of the isolates (n = 82) were
      highly resistant and only 4 isolates (5%) decreased their MIC in the presence of
      bLF. None of the trimethoprim-sulfamethoxazole resistant strains became
      susceptible in the presence of LF. The decrease in the MIC in the presence of bLF
      seems to depend on the mechanisms of action of each antibiotic. In vivo studies
      are needed to further evaluate bLF as a coadjuvant to antibiotic treatment of
      resistant Shigella.

PMID- 22397496
TI  - Cisplatin resistance induced by decreased apoptotic activity in non-small-cell
      lung cancer cell lines.
AB  - We have investigated defective steps in apoptosis that might account for the
      development of resistance. For this purpose, A549 and Calu1 NSCLC (non-small-cell
      lung cancer) cell lines were treated with cisplatin to obtain resistant sub
      lines. Gene expression profiles and the phosphorylation status of the BAD (Bcl
      2/Bcl-XL-antagonist, causing cell death) protein were determined for each cell
      line. Cell death and cytochrome c release were analysed after treating cell lines
      with their appropriate cisplatin doses. Gene expression of BAD, Bid, caspases 4
      and 6 were clearly decreased in the resistant cell lines, and the differential
      phosphorylation status of BAD also seemed to play a role in the development of
      cisplatin resistance. Since this is a new cisplatin-resistant Calu1 cell line, it
      is noteworthy that DNA fragmentation, apoptotic cell ratio and cytochrome c
      levels were most decreased in the CR-Calu1 cell line.

PMID- 22397497
TI  - Factors determining the effectiveness of oral ciclosporin in the treatment of
      severe childhood atopic dermatitis.
AB  - Ciclosporin is used to treat severe atopic dermatitis (AD) where conventional
      therapy is either ineffective or inappropriate. Response to treatment is variable
      and the factors determining responsiveness are currently unclear. The aim of this
      study was to determine which children with severe AD are most responsive. A
      cohort of 35 children with severe AD who were given oral ciclosporin was
      retrospectively surveyed. SCORAD index was used to assess severity prior to and
      after treatment. Demographic and clinical data were correlated with clinical
      response. Ciclosporin resulted in a sustained reduction in SCORAD index of 91 (67
      100)% in children where clinical skin infection was the main trigger and in whom
      the infection was effectively eradicated with antibiotics. If infection persisted
      or recurred the reduction in SCORAD index was only 44 (41-83)%. Children in whom
      their AD was triggered by other factors had a poor response to ciclosporin with
      reduction in SCORAD index of 8 (1-39)%. Oral ciclosporin is most effective in
      children with infection-driven AD in whom the infection is brought under control.
      In cases where the infection recurs or where the main triggers are non
      infectious, response to ciclosporin is poorer.

PMID- 22397498
TI  - Plant extracts, spices, and essential oils inactivate Escherichia coli O157:H7
      and reduce formation of potentially carcinogenic heterocyclic amines in cooked
      beef patties.
AB  - Meats need to be heated to inactivate foodborne pathogens such as  Escherichia
      coli  O157:H7. High-temperature treatment used to prepare well-done meats
      increases the formation of carcinogenic heterocyclic amines (HCAs). We evaluated
      the ability of plant extracts, spices, and essential oils to simultaneously
      inactivate  E. coli  O157:H7 and suppress HCA formation in heated hamburger
      patties. Ground beef with added antimicrobials was inoculated with  E. coli 
      O157:H7 (10(7) CFU/g). Patties were cooked to reach 45  degrees C at the
      geometric center, flipped, and cooked for 5 min. Samples were then taken for
      microbiological and mass spectrometry analysis of HCAs. Some compounds were
      inhibitory only against  E. coli  or HCA formation, while some others inhibited
      both. Addition of 5% olive or apple skin extracts reduced  E. coli  O157:H7
      populations to below the detection limit and by 1.6 log CFU/g, respectively.
      Similarly, 1% lemongrass oil reduced  E. coli  O157:H7 to below detection limits,
      while clove bud oil reduced the pathogen by 1.6 log CFU/g. The major heterocyclic
      amines 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl
      6-phenylimidazo[4,5-b]pyridine (PhIP) were concurrently reduced with the addition
      of olive extract by 79.5% and 84.3% and with apple extract by 76.1% and 82.1%,
      respectively. Similar results were observed with clove bud oil: MeIQx and PhIP
      were reduced by 35% and 52.1%, respectively. Addition of onion powder decreased
      formation of PhIP by 94.3%. These results suggest that edible natural plant
      compounds have the potential to prevent foodborne infections as well as
      carcinogenesis in humans consuming heat-processed meat products.

PMID- 22397499
TI  - beta,gamma-CHF- and beta,gamma-CHCl-dGTP diastereomers: synthesis, discrete 31P
      NMR signatures, and absolute configurations of new stereochemical probes for DNA
      polymerases.
AB  - Deoxynucleoside 5'-triphosphate analogues in which the beta,gamma-bridging oxygen
      has been replaced with a CXY group are useful chemical probes to investigate DNA
      polymerase catalytic and base-selection mechanisms. A limitation of such probes
      has been that conventional synthetic methods generate a mixture of diastereomers
      when the bridging carbon substitution is nonequivalent (X ? Y). We report here a
      general solution to this long-standing problem with four examples of beta,gamma
      CXY dNTP diastereomers: (S)- and (R)-beta,gamma-CHCl-dGTP (12a-1/12a-2) and (S)-
      and (R)-beta,gamma-CHF-dGTP (12b-1/12b-2). Central to their preparation was
      conversion of the prochiral parent bisphosphonic acids to the P,C
      dimorpholinamide derivatives 7 of their (R)-mandelic acid monoesters, which
      provided access to the individual diastereomers 7a-1, 7a-2, 7b-1, and 7b-2 by
      preparative HPLC. Selective acidic hydrolysis of the P-N bond then afforded
      "portal" diastereomers, which were readily coupled to morpholine-activated dGMP.
      Removal of the chiral auxiliary by H(2) (Pd/C) gave the four individual
      diastereomeric nucleotides 12, which were characterized by (31)P, (1)H, and (19)F
      NMR spectroscopy and by mass spectrometry. After treatment with Chelex-100 to
      remove traces of paramagnetic ions, at pH ~10 the diastereomer pairs 12a,b
      exhibit discrete P(alpha) and P(beta)(31)P resonances. The more upfield P(alpha)
      and more downfield P(beta) resonances (and also the more upfield (19)F NMR
      resonance in 12b) are assigned to the R configuration at the P(beta)-CHX-P(gamma)
      carbons on the basis of the absolute configurations of the individual
      diastereomers as determined from the X-ray crystallographic structures of their
      ternary complexes with DNA and polymerase beta.

PMID- 22397500
TI  - Foraging success in a wild species of bird varies depending on which eye is used
      for anti-predator vigilance.
AB  - Brain lateralisation in animals with laterally placed eyes often leads to
      preferential eye use for ecologically relevant tasks such as monitoring predators
      and companions. Few studies of preferential eye use have been conducted in the
      wild and it is not clear if such preferences in the wild are widespread, how
      individuals can benefit from them, and which ecological factors influence their
      evolution. In a wild species of bird the extent to which foraging success varied
      depending on which eye is used during concomitant anti-predator vigilance was
      examined. When foraging in open mudflats, semipalmated sandpipers (Calidris
      pusilla) are frequently exposed to predation attempts by falcons (Falco spp) that
      originate from the tree cover bordering mudflats. Sandpipers spread along the
      receding tideline and can face the riskier side of their habitat primarily with
      the left or the right eye as they forage. If foraging is mostly incompatible with
      vigilance, the rate at which prey items are collected should decrease when birds
      use their less-preferred eye to scan cover. If foraging and vigilance can be
      carried out simultaneously, time spent foraging should not be affected but the
      efficiency with which their burrowing amphipod prey are located may be reduced,
      thus leading to decreased capture rate. Birds facing the riskier side of the
      habitat with their right eye captured significantly more prey than those scanning
      the same side with their left eye. Specialised eye use in sandpipers may allow
      individuals to perform simultaneous tasks, such as foraging and vigilance, more
      efficiently.

PMID- 22397501
TI  - Chewing areca nut increases the risk of coronary artery disease in Taiwanese men:
      a case-control study.
AB  - BACKGROUND: Areca nut chewing has been reported to be associated with obesity,
      metabolic syndrome, hypertension, and cardiovascular mortality in previous
      studies. The aim of this study was to examine whether chewing areca nut increases
      the risk of coronary artery disease (CAD) in Taiwanese men. METHODS: This study
      is a hospital-based case-control study. The case patients were male patients
      diagnosed in Taiwan between 1996 and 2009 as having a positive Treadmill exercise
      test or a positive finding on the Thallium-201 single-photon emission computed
      tomography myocardial perfusion imaging. The case patients were further evaluated
      by coronary angiography to confirm their CAD. Obstructive CAD was defined as a >=
      50% decrease in the luminal diameter of one major coronary artery. The patients
      who did not fulfill the above criteria of obstructive CAD were excluded.The
      potential controls were males who visited the same hospital for health check-ups
      and had a normal electrocardiogram but no history of ischemic heart disease or
      CAD during the time period that the case patients were diagnosed. The eligible
      controls were randomly selected and frequency-matched with the case patients
      based on age. Multiple logistic regression analyses were used to estimate the
      odds ratio of areca nut chewing and the risk of obstructive CAD. RESULTS: A total
      of 293 obstructive CAD patients and 720 healthy controls, all men, were analyzed.
      Subjects who chewed areca nut had a 3.5-fold increased risk (95% CI = 2.0-6.2) of
      having obstructive CAD than those without, after adjusting for other significant
      covariates. The dose-response relationship of chewing areca nut and the risk of
      obstructive CAD was also noted. After adjusting for other covariates, the 2-way
      additive interactions for obstructive CAD risk were also significant between
      areca nut use and cigarette smoking, hypertension and dyslipidemia. CONCLUSIONS:
      Long-term areca nut chewing was an independent risk factor of obstructive CAD in
      Taiwanese men. Interactive effects between chewing areca nut and cigarette
      smoking, hypertension, and dyslipidemia were also observed for CAD risk. Further
      exploration of their underlying mechanisms is necessary.

PMID- 22397503
TI  - Processing-structure-property correlations of polyethersulfone/perfluorosulfonic
      acid nanofibers fabricated via electrospinning from polymer-nanoparticle
      suspensions.
AB  - Polyethersulfone (PES)/perfluorosulfonic acid (PFSA) nanofiber membranes were
      successfully fabricated via electrospinning method from polymer solutions
      containing dispersed calcium carbonate (CaCO(3)) nanoparticles. ATR-FTIR spectra
      indicated that the nanoparticles mainly existed on the external surface of the
      nanofibers and could be removed completely by acid treatment. Surface roughness
      of both the nanofibers and the nanofiber membranes increased with the CaCO(3)
      loading. Although FTIR spectra showed no special interaction between sulfonic
      acid (-SO(3)) groups and CaCO(3) nanoparticles, XPS measurement demonstrated that
      the content of -SO(3) groups on external surface of the acid-treated nanofibers
      was enhanced by increasing CaCO(3) loading in solution. Besides, the acid-treated
      nanofiber membranes were performed in esterification reactions, and exhibited
      acceptable catalytic performance due to the activity of -SO(3)H groups on the
      nanofiber surface. More importantly, this type of membrane was very easy to
      separate and recover, which made it a potential substitution for traditional
      liquid acid catalysts.

PMID- 22397502
TI  - Targeting of the non-mutated tumor antigen HER2/neu to mature dendritic cells
      induces an integrated immune response that protects against breast cancer in
      mice.
AB  - INTRODUCTION: Given their relative simplicity of manufacture and ability to be
      injected repeatedly, vaccines in a protein format are attractive for breast and
      other cancers. However, soluble human epidermal growth factor receptor (HER2)/neu
      protein as a vaccine has not been immunogenic. When protein is directly targeted
      to antigen uptake receptors, such as DEC205 (DEC), efficient processing and
      presentation of antigen take place. The aim of this study was to determine the
      immunogenicity of a HER2 protein vaccine that directly targets to DEC+ dendritic
      cells (DCs) in a mouse breast cancer model. METHODS: We genetically engineered
      the HER2 extracellular domain into a monoclonal antibody specific for DEC (DEC
      HER2). Mice of various genetic backgrounds were immunized with DEC-HER2 in
      combination with DC maturation stimuli (poly IC +/- CD40 Ab). Vaccine-induced T
      cell immunity was determined by analyzing the ability of CD4+/CD8+ T cell to
      produce interferon (IFN)-gamma and proliferate upon antigen rechallenge. Sera
      were assessed for the presence of antigen specific antibody (Ab). For vaccine
      efficacy, FVB/N mice were immunized with DEC-HER2 in combination with poly IC and
      protection against neu-expressing mammary tumors was assessed. Protection
      mechanisms and tumor-specific T cell responses were also evaluated. RESULTS: We
      demonstrate that DEC-HER2 fusion mAb, but not Ctrl Ig-HER2, elicits strong, broad
      and multifunctional CD4+ T cell immunity, CD8+ T cell responses, and humoral
      immunity specific for HER2 antigen. Cross-reactivity to rat neu protein was also
      observed. Importantly, mice xeno-primed with DEC-HER2 were protected from a neu
      expressing mammary tumor challenge. Both CD4+ and CD8+ T cells mediated the tumor
      protection. Robust anti-tumor T cell immunity was detected in tumor protected
      mice. CONCLUSIONS: Immunization of mice with HER2 protein vaccine targeting DEC+
      DCs in vivo induced high levels of T- and B-cell immunity. Non-targeted HER2
      protein was poorly immunogenic for CD4+ and CD8+ T cells. This vaccination
      approach provided long-term survival benefit for mice challenged with neu
      expressing tumor following as little as 2.7 MUg of HER2 protein incorporated in
      the vaccine. Vaccine-induced CD4+ and CD8+ T cells were both essential for tumor
      protection. This immunization strategy demonstrates great potential towards the
      development of vaccines for breast cancer patients.

PMID- 22397504
TI  - Environmental tobacco smoke as a source of polycyclic aromatic hydrocarbons in
      settled household dust.
AB  - Environmental tobacco smoke is a major contributor to indoor air pollution. Dust
      and surfaces may remain contaminated long after active smoking has ceased (called
      'thirdhand' smoke). Polycyclic aromatic hydrocarbons (PAHs) are known
      carcinogenic components of tobacco smoke found in settled house dust (SHD). We
      investigated whether tobacco smoke is a source of PAHs in SHD. House dust was
      collected from 132 homes in urban areas of Southern California. Total PAHs were
      significantly higher in smoker homes than nonsmoker homes (by concentration: 990
      ng/g vs 756 ng/g, p = 0.025; by loading: 1650 ng/m(2) vs 796 ng/m(2), p = 0.012).
      We also found significant linear correlations between nicotine and total PAH
      levels in SHD (concentration, R(2) = 0.105; loading, R(2) = 0.385). Dust
      collected per square meter (g/m(2)) was significantly greater in smoker homes and
      might dilute PAH concentration in SHD inconsistently. Therefore, dust PAH loading
      (ng PAH/m(2)) is a better indicator of PAH content in SHD. House dust PAH
      loadings in the bedroom and living room in the same home were significantly
      correlated (R(2) = 0.468, p < 0.001) suggesting PAHs are distributed by tobacco
      smoke throughout a home. In conclusion, tobacco smoke is a source of PAHs in SHD,
      and tobacco smoke generated PAHs are a component of thirdhand smoke.

PMID- 22397505
TI  - Starting on haemodialysis: a qualitative study to explore the experience and
      needs of incident patients.
AB  - Dialysis can be very stressful with the initial months onto treatment being
      highly critical in terms of both adaptation and mortality. This qualitative study
      aimed to explore the lived experiences of incident haemodialysis patients in
      Singapore. Topics related to the end-stage renal disease diagnosis and
      haemodialysis treatment were raised with 13 incident haemodialysis patients in
      the form of semi-structured interviews, and interpretative phenomenological
      analysis was undertaken as the framework for data analysis. Emotional distress,
      treatment-related concerns and social support emerged as main issues following a
      critical review of themes. Our study revealed that incident haemodialysis
      patients have emotional and informational needs, highlighting the importance of
      intervention programmes in particular to this patient group to promote better
      psychosocial adjustment to the disease and its treatment.

PMID- 22397506
TI  - Anaphylactic reactions to oligosaccharides in red meat: a syndrome in evolution.
AB  - OBJECTIVE: While most allergic responses to food are directed against protein
      epitopes and occur within 30 minutes of ingesting the allergen, recent studies
      suggest that delayed reactions may occur, sometimes mediated by IgE antibodies
      directed against carbohydrate moieties. The objective of this review is to
      summarize the clinical features and management of delayed hypersensitivity
      reactions to mammalian meat mediated by IgE antibodies to galactose-alpha 1,3
      galactose (alpha-gal), an oligosaccharide. METHODS: A PubMed search was conducted
      with MeSH terms: galactosyl-(1,3) galactose, oligosaccharides, cetuximab,
      allergy/hypersensitivity, and anaphylaxis. Reported cases with alpha-gal-mediated
      reactions were reviewed. This research study was approved by the Institutional
      Review Board of East Tennessee State University. RESULTS: Thirty-two cases of
      adults presenting with red-meat induced allergy thought to be related to
      oligosaccharides have been reported in the literature so far, making this a rare
      and evolving syndrome. Most of these patients demonstrated delayed reactions to
      beef, as was seen in the case reported by us in this manuscript. IgE specific to
      alpha-gal was identified in most patients with variable response to skin testing
      with beef and pork. Inhibition studies in some cases showed that the IgE
      antibodies to beef were directed towards alpha-gal in the meat rather than the
      protein. The patients often reported history of tick bites, the significance of
      which is unclear at present. Reactions to cetuximab, a monoclonal antibody, are
      mediated by a similar mechanism, with IgE antibodies directed against an alpha
      gal moiety incorporated in the drug structure. CONCLUSION: Alpha-gal is an
      oligosaccharide recently incriminated in delayed anaphylactic reactions to
      mammalian meats such as to beef, pork, and lamb. It appears that anaphylactic
      reactions to the anti-cancer biological agent, cetuximab, may be linked
      mechanistically to the same process. More studies are required to understand the
      underlying molecular basis for these delayed reactions in specific, and their
      broader implications for host defense in general.

PMID- 22397507
TI  - Combination therapy with metformin plus vildagliptin in type 2 diabetes mellitus.
AB  - INTRODUCTION: Type 2 diabetes mellitus (T2DM) is pathophysiologically
      characterized by a combination of insulin resistance and beta-cell dysfunction.
      Consequently, a proper treatment of such a disease should target both of these
      defects. Dipeptidyl peptidase-4 (DPP-4) inhibitors are among the most recent
      additions to the therapeutic options for T2DM and are able to increase
      circulating levels of glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP), thus stimulating glucose-dependent insulin
      secretion. AREAS COVERED: This paper provides an overview of the clinical results
      of combination therapy with metformin and the DPP-4 inhibitor vildagliptin in
      T2DM patients. EXPERT OPINION: Vildagliptin-metformin single-tablet combination
      is indicated for the treatment of T2DM patients not achieving a sufficient
      glycemic control at their maximally tolerated dose of metformin. Results from
      clinical trials provide evidence of vildagliptin efficacy administered in
      addition to metformin, as either first- or second-line treatment. The
      vildagliptin-metformin association seems to have favorable effects on beta-cell
      function and is characterized by good safety and tolerability profiles when
      compared with other antidiabetic agents. Of note, data available suggest that
      administration of fixed-dose combination products, together with the low
      incidence of adverse gastrointestinal events, may improve compliance and
      adherence of patients to therapy, resulting in an improved metabolic control.

PMID- 22397508
TI  - Evaluation of professional bra fitting criteria for bra selection and fitting in
      the UK.
AB  - A correctly fitting bra is essential for good health; this study investigates the
      use of professional bra fitting criteria to establish best-fit in an underwire
      bra commonly sold in the UK. A comparison was made between women's bra size as
      measured by the traditional bra fitting method with their recommended bra size
      based on professional bra fitting criteria. Forty-five female participants were
      recruited; their mode self-reported bra size was 34DD. Participants were measured
      in their own bra using the traditional bra-fitting method to establish their
      'traditional size'. A 'best-fit' bra size was recorded for participants based on
      professional bra fitting criteria. Significant differences were found between
      traditional and best-fit cup and band sizes (p < 0.001); the traditional method
      of bra fitting overestimated band size and underestimated cup size. As band size
      increased the traditional method also became more inaccurate (p < 0.001). It is
      recommended that women are educated in assessing their own bra fit using
      professional bra fitting criteria and less emphasis placed on determining
      absolute bra size.    Practitioner Summary: This is the first study to
      investigate using professional bra fitting criteria to establish best-fit in an
      underwired bra commonly sold in the UK. The traditional method of bra fitting was
      found to be inadequate, especially for larger-breasted women; the use of
      professional bra fitting criteria should be encouraged.

PMID- 22397509
TI  - Occurrence and characteristics of extended-spectrum beta-lactamase (ESBL)
      producing Enterobacteriaceae in food producing animals, minced meat and raw milk.
AB  - BACKGROUND: The impact of food animals as a possible reservoir for extended
      spectrum beta-lactamase (ESBL) producing Enterobacteriaceae, and the
      dissemination of such strains into the food production chain need to be assessed.
      In this study 334 fecal samples from pigs, cattle, chicken and sheep were
      investigated at slaughter. Additionally, 100 raw milk samples, representing bulk
      tank milk of 100 different dairy farms, 104 minced meat (pork and beef) samples
      and 67 E. coli isolates from cattle E. coli mastitis were analyzed. RESULTS: As
      many as 15.3% of the porcine, 13.7% of the bovine, 8.6% of the sheep and 63.4% of
      the chicken fecal samples yielded ESBL producers after an enrichment step. In
      contrast, none of the minced meat, none of the bulk tank milk samples and only
      one of the mastitis milk samples contained ESBL producing strains. Of the total
      of 91 isolates, 89 were E. coli, one was Citrobacter youngae and one was
      Enterobacter cloacae. PCR analysis revealed that 78 isolates (85.7%) produced CTX
      M group 1 ESBLs while six isolates (6.6%) produced CTX-M group 9 enzymes. Five
      detected ESBLs (5.5%) belonged to the SHV group and 2 isolates (2.2%) contained a
      TEM-type enzyme. A total of 27 CTX-M producers were additionally PCR-positive for
      TEM-beta-lactamase. The ESBL-encoding genes of 53 isolates were sequenced of
      which 34 produced CTX-M-1, 6 produced CTX-M-14, 5 produced CTX-M-15 and also 5
      produced SHV-12. Two isolates produced TEM-52 and one isolate expressed a novel
      CTX-M group 1 ESBL, CTX-M-117. One isolate--aside from a CTX-M ESBL-- contained
      an additional novel TEM-type broad-spectrum beta-lactamase, TEM-186. CONCLUSIONS:
      The relatively high rates of ESBL producers in food animals and the high genetic
      diversity among these isolates are worrisome and indicate an established
      reservoir in farm animals.

PMID- 22397511
TI  - Slowly relaxing local structure (SRLS) analysis of 15N-H relaxation from the
      prototypical small proteins GB1 and GB3.
AB  - 15N-H relaxation parameters from the first (GB1) and third (GB3) immunoglobulin
      binding domains of streptococcal protein G were analyzed previously with the
      traditional model-free (MF) method. These proteins comprise an alpha-helix and a
      four-stranded beta-sheet. An extensive study of GB1 (GB3) used combined three
      field (five-field) data acquired in the 278-323 K range (at 297 K). For
      successful analysis of the GB3 data, it was necessary to allow for variations in
      the 15N chemical shift anisotropy (CSA) tensor and virtually eliminate the local
      motion. In the case of GB1, the spectral density was parametrized. Here, we
      analyze these data with the slowly relaxing local structure (SRLS) approach,
      which is the generalization of MF in allowing for general tensorial properties,
      and accounting for mode-coupling. A standard (featuring constant magnetic
      tensors) SRLS fitting scheme is used. This analysis accounts for the important
      asymmetry of the local spatial restrictions; it provides physical order
      parameters, local diffusion rates, related activation energies, and key features
      of local geometry. Using data from GB3 we show that the main local ordering axis
      is C(i-1)(alpha) - C(i)(alpha), and the average axial (rhombic) order parameter
      is -0.457 +/- 0.017 (1.156 +/- 0.015) for the alpha-helix and -0.484 +/- 0.002
      (1.10 +/- 0.04) for the rest of the polypeptide chain. The N-H bonds within
      (outside of) the alpha-helix reorient locally with an average correlation time,
      (tau), of 310 (130) ps, as compared to 3.33 ns for the global tumbling. Several N
      H bonds in the loops beta1/beta2, beta2/alpha-helix, and alpha-helix/beta3 have
      (tau) of 380, 320, and 750 ps, respectively. The distinctive experimental data of
      the alpha-helix are due to relatively weak and substantially rhombic local
      ordering and slow local motion. For GB1, we derive activation energies from local
      diffusion rates. They are 43.3 +/- 7.1 kJ/mol for the beta-strands, 24.7 +/- 3.9
      kJ/mol for the alpha-helix (and approximately for the loop beta3/beta4), and 18.9
      +/- 1.8 kJ/mol for the other loops. The physical SRLS description provides new
      insights into the backbone dynamics of GB1 and GB3 in particular, and proteins in
      general.

PMID- 22397512
TI  - The effects of mortality reminders on posttraumatic growth and finding benefits
      among patients with life-threatening illness and their caregivers.
AB  - Individuals confronted with a life-threatening illness often report posttraumatic
      growth (PTG) or finding benefits in disease. These positive evaluations of
      personal strength, perceptions of improved personal relations and new
      possibilities may represent a defensive response (cf Janus-face model). Three
      studies investigated the effects of mortality reminders on reports of PTG or
      benefit findings among people living with life-threatening illness or their
      caregivers. 80 people living with HIV (study 1), 164 breast cancer survivors
      (study 2) and 50 family caregivers for a patient with huntington disease (study
      3) were randomly assigned to the experimental (mortality reminders) or control
      conditions. Across three studies, those exposed to mortality reminders reported
      lower PTG or benefit finding, compared to the controls. These effects were
      moderated by time elapsed since diagnosis: mortality reminders led to lower
      PTG/benefit finding among those who received the diagnosis more recently. The
      results provide an insight into the defensive character of PTG/finding benefits
      in illness and changes in the function of these beliefs over time elapsing since
      diagnosis.

PMID- 22397513
TI  - Patterns of sequence variation within the Neisseria meningitidis lactoferrin
      binding proteins.
AB  - Lactoferrin binding proteins A and B (LbpA and LbpB) compose the lactoferrin
      receptor of the obligate human pathogen  Neisseria meningitidis . This receptor
      is thought to be important for colonization and initiation of invasive disease
      because of its role in acquiring host iron and providing protection from the
      cationic peptide, lactoferricin. By virtue of its function, the receptor is
      accessible to the host immune system and displays substantial sequence variation.
      In this study, we analyzed a broad collection of LbpAs (62) and LbpBs (101) to
      determine the distribution of sequence variation within each protein and to
      search for patterns between sequence similarity and strain typing. The sequence
      variation in LbpA was predominantly observed in 3 surface loops and,
      surprisingly, in the N-terminal region immediately upstream of the predicted TonB
      box. The analysis of LbpB revealed that the variability was distributed
      throughout the protein, particularly in the highly variable negatively charged
      regions in the C-lobe, but otherwise was greater in the N-lobe than the C-lobe.
      There was no readily identifiable correlation between the sequence variation
      within LbpA, LbpB, multi-locus sequence type, or serogroup.

PMID- 22397515
TI  - A standardised approach for the dispersion of titanium dioxide nanoparticles in
      biological media.
AB  - We describe a comprehensive optimisation study culminating in a standardised and
      validated approach for the preparation of titanium dioxide (TiO2) nanoparticle
      dispersions in relevant biological media. This study utilises a TiO2 reference
      nanomaterial based on a commercially available powder that has been widely
      examined in both acute and chronic toxicity studies. The dispersion approach as
      presented here satisfies four key harmonisation requirements not previously
      addressed: (1) method transferability, based in part on the use of a sonication
      energy calibration method that allows for power measurement and reporting in a
      device-independent manner; (2) optimisation of sonication parameters and thorough
      method validation in terms of particle size distribution, pH, isoelectric point,
      concentration range and batch variability; (3) minimisation of sonolysis side
      effects by elimination of organics during sonication and (4) characterisation of
      nanoparticle agglomeration under various dispersion conditions by use of laser
      diffraction spectrometry, an in situ size characterisation technique that
      provides advantages over other techniques more commonly employed within the
      context of nanotoxicology (e.g. dynamic light scattering). The described
      procedure yields monomodal, nanoscale, protein-stabilised nanoparticle
      dispersions in biological media that remain stable for at least 48 h (acute
      testing timeframe) under typical incubation conditions.

PMID- 22397516
TI  - Deep peeling using phenol versus percutaneous collagen induction combined with
      trichloroacetic acid 20% in atrophic post-acne scars; a randomized controlled
      trial.
AB  - BACKGROUND: Deep peeling using phenol and percutaneous collagen induction (PCI)
      are used in treating acne scars. AIM: To compare deep peeling using phenol and
      PCI combined with trichloroacetic acid (TCA) 20% in treating atrophic acne scars.
      METHODS: 24 patients with post-acne atrophic scars were randomly divided into two
      groups; group 1 was subjected to one session of deep peeling using phenol, and
      group 2 was subjected to four sessions of PCI combined with TCA 20%. As a
      secondary outcome measure, side effects were recorded and patients were asked to
      assess their % of improvement by a questionnaire completed 8 months after the
      procedure. RESULTS: Scar severity scores improved by a mean of 75.12% (p < 0.001)
      in group 1 and a mean of 69.43% (p < 0.001) in group 2. Comparing the degree of
      improvement in different types of scars, within the same group after treatment,
      revealed a significant highest degree of improvement in the rolling type (p =
      0.005) in group 2. CONCLUSION: Deep peeling using phenol and PCI with TCA 20%
      were effective in treating post-acne atrophic scars.

PMID- 22397517
TI  - Synthesis and incorporation into cyclic peptides of tolan amino acids and their
      hydrogenated congeners: construction of an array of A-B-loop mimetics of the
      Cepsilon3 domain of human IgE.
AB  - The disruption of the human immunolobulin E-high affinity receptor I (IgE
      FcepsilonRI) protein-protein interaction (PPI) is a validated strategy for the
      development of anti asthma therapeutics. Here, we describe the synthesis of an
      array of conformationally constrained cyclic peptides based on an epitope of the
      A-B loop within the Cepsilon3 domain of IgE. The peptides contain various tolan
      (i.e., 1,2-biarylethyne) amino acids and their fully and partially hydrogenated
      congeners as conformational constraints. Modest antagonist activity (IC(50) ~660
      MUM) is displayed by the peptide containing a 2,2'-tolan, which is the one
      predicted by molecular modeling to best mimic the conformation of the native A-B
      loop epitope in IgE.

PMID- 22397518
TI  - Organogel-emulsions with mixtures of beta-sitosterol and gamma-oryzanol:
      influence of water activity and type of oil phase on gelling capability.
AB  - In this study, water-in-oil emulsions were prepared from water containing
      different salt concentrations dispersed in an oil phase containing a mixture of
      beta-sitosterol and gamma-oryzanol. In pure oil, the beta-sitosterol and gamma
      oryzanol molecules self-assemble into tubular microstructures to produce a firm
      organogel. However, in the emulsion, the water molecules bind to the beta
      sitosterol molecules, forming monohydrate crystals that hinder the formation of
      the tubules and resulting in a weaker emulsion-gel. Addition of salt to the water
      phase decreases the water activity, thereby suppressing the formation of
      sitosterol monohydrate crystals even after prolonged storage times (~1 year).
      When the emulsions were prepared with less polar oils, the tubular microstructure
      was promoted, which significantly increased the firmness of the emulsion-gel. The
      main conclusion of this study is that the formation of oryzanol and sitosterol
      tubular microstructure in the emulsion can be promoted by reducing the water
      activity and/or by using oils of low polarity.

PMID- 22397519
TI  - Intra-arrest hypothermia during cardiac arrest: a systematic review.
AB  - INTRODUCTION: Therapeutic hypothermia is largely used to protect the brain
      following return of spontaneous circulation (ROSC) after cardiac arrest (CA), but
      it is unclear whether we should start therapeutic hypothermia earlier, that is,
      before ROSC. METHODS: We performed a systematic search of PubMed, EMBASE, CINAHL,
      the Cochrane Library and Ovid/Medline databases using "arrest" OR "cardiac
      arrest" OR "heart arrest" AND "hypothermia" OR "therapeutic hypothermia" OR
      "cooling" as keywords. Only studies using intra-arrest therapeutic hypothermia
      (IATH) were selected for this review. Three authors independently assessed the
      validity of included studies and extracted data regarding characteristics of the
      studied cohort (animal or human) and the main outcomes related to the use of
      IATH: Mortality, neurological status and cardiac function (particularly, rate of
      ROSC). RESULTS: A total of 23 animal studies (level of evidence (LOE) 5) and five
      human studies, including one randomized controlled trial (LOE 1), one
      retrospective and one prospective controlled study (LOE 3), and two prospective
      studies without a control group (LOE 4), were identified. IATH improved survival
      and neurological outcomes when compared to normothermia and/or hypothermia after
      ROSC. IATH was also associated with improved ROSC rates and with improved cardiac
      function, including better left ventricular function, and reduced myocardial
      infarct size, when compared to normothermia. CONCLUSIONS: IATH improves survival
      and neurological outcome when compared to normothermia and/or conventional
      hypothermia in experimental models of CA. Clinical data on the efficacy of IATH
      remain limited.

PMID- 22397520
TI  - Can work ability explain the social gradient in sickness absence: a study of a
      general population in Sweden.
AB  - BACKGROUND: Understanding the reasons for the social gradient in sickness absence
      might provide an opportunity to reduce the general rates of sickness absence. The
      complete explanation for this social gradient still remains unclear and there is
      a need for studies using randomized working population samples. The main aim of
      the present study was to investigate if self-reported work ability could explain
      the association between low socioeconomic position and belonging to a sample of
      new cases of sick-listed employees. METHODS: The two study samples consisted of a
      randomized working population (n = 2,763) and a sample of new cases of sick
      listed employees (n = 3,044), 19-64 years old. Both samples were drawn from the
      same randomized general population. Socioeconomic status was measured with
      occupational position and physical and mental work ability was measured with two
      items extracted from the work ability index. RESULTS: There was an association
      between lower socioeconomic status and belonging to the sick-listed sample among
      both women and men. In men the crude Odds ratios increased for each downwards
      step in socioeconomic status, OR 1.32 (95% CI 0.98-1.78), OR 1.53 (1.05-2.24), OR
      2.80 (2.11-3.72), and OR 2.98 (2.27-3.90). Among women this gradient was not as
      pronounced. Physical work ability constituted the strongest explanatory factor
      explaining the total association between socioeconomic status and being sick
      listed in women. However, among men, the association between skilled non-manual,
      OR 2.07 (1.54-2.78), and non-skilled manual, OR 2.03 (1.53-2.71) positions in
      relation to being sick-listed remained. The explanatory effect of mental work
      ability was small. Surprisingly, even in the sick-listed sample most respondents
      had high mental and physical work ability. CONCLUSIONS: These results suggest
      that physical work ability may be an important key in explaining the social
      gradient in sickness absence, particularly in women. Hence, it is possible that
      the factors associated with the social gradient in sickness absence may differ,
      to some extent, between women and men.

PMID- 22397521
TI  - Color Tuning in rhodopsins: the origin of the spectral shift between the chloride
      bound and anion-free forms of halorhodopsin.
AB  - Detailed knowledge of the molecular mechanisms that control the spectral
      properties in the rhodopsin protein family is important for understanding the
      functions of these photoreceptors and for the rational design of artificial
      photosensitive proteins. Here we used a high-level ab initio QM/MM method to
      investigate the mechanism of spectral tuning in the chloride-bound and anion-free
      forms of halorhodopsin from  Natronobacterium pharaonis  (phR) and the
      interprotein spectral shift between them. We demonstrate that the chloride ion
      tunes the spectral properties of phR via two distinct mechanisms: (i)
      electrostatic interaction with the chromophore, which results in a 95 nm
      difference between the absorption maxima of the two forms, and (ii) induction of
      a structural reorganization in the protein, which changes the positions of
      charged and polar residues and reduces this difference to 29 nm. The present
      study expands our knowledge concerning the role of the reorganization of the
      internal H-bond network for color tuning in general and provides a detailed
      investigation of the tuning mechanism in phR in particular.

PMID- 22397522
TI  - Anthropogenic atmospheric emissions of antimony and its spatial distribution
      characteristics in China.
AB  - An integrated inventory of atmospheric antimony (Sb) emissions from anthropogenic
      activities in China is compiled for the years 2005-2009. Emissions are estimated
      for all major anthropogenic sources for the first time. We estimate that the
      national emissions of antimony are 818 metric tons (t) in 2009, with the largest
      contribution from coal combustion at 61.8% of the total, while 26.7% of Sb is
      emitted from nonferrous metals smelting. Emissions are heaviest in Guizhou
      province, mainly due to small-scale combustion of high-Sb coal without emission
      control devices, and in Hunan province, where extensive smelting occurs.
      Furthermore, Sb emissions from 2188 large point sources and area sources are
      distributed within latitude/longitude-based grids with a resolution of 30 min *
      30 min where Sb emissions are largely concentrated in highly populated and
      industrialized southwestern China, the east central region, and coastal areas.
      The uncertainties in our bottom-up inventory are quantified as -11% to 40% by
      Monte Carlo simulation. We recommend continuous field testing of coal combustors
      and smelters in China to improve the accuracy of these estimates.

PMID- 22397523
TI  - Proteomic analysis of soybean defense response induced by cotton worm (prodenia
      litura, fabricius) feeding.
AB  - BACKGROUND: Cotton worm is one of the main insects of soybean in southern China.
      Plants may acquire defense mechanisms that confer protection from predation by
      herbivores. Induced responses can lead to increased resistance against herbivores
      in many species. This study focuses on searching changed proteins in soybean
      defense response induced by cotton worm feeding. RESULTS: Ten protein spots that
      are changed in abundance in response to cotton worm feeding were identified by
      Two-dimensional gel electrophoresis (2-DE). A total of 11 unique proteins from
      these spots were identified by MALDI-TOF MS. The mRNA and protein relative
      expression levels of most changed proteins were up-regulated. These proteins were
      mainly involved in physiological processes, including active oxygen removal,
      defense signal transduction, and metabolism regulation. CONCLUSION: This is the
      first proteomic analysis of the soybean defense response induced by cotton worm.
      The differentially expressed proteins could work together to play a major role in
      the induced defense response. PAL and SAMS were up-regulated at both the protein
      and mRNA levels. These genes can be strongest candidates for further functional
      research.

PMID- 22397524
TI  - Reliability of the strengths and difficulties questionnaire among Finnish 4-9
      year-old children.
AB  - BACKGROUND: Early recognition of children's mental health problems calls for
      structured methods in front line services. The Strengths and Difficulties
      Questionnaire (SDQ) is a commonly used short questionnaire in screening child's
      mental difficulties. AIM: To test the reliability and descriptive properties of
      the SDQ in a community sample of Finnish 4-9-year-old children (n = 4178).
      METHODS: Both parents, two teachers in day-care or a teacher at school completed
      the SDQ. To control for possible bias, public health nurses rated their concern
      about every child's mental health, including non-participants. RESULTS: The
      internal consistencies of the SDQ total score in all informants' reports were
      satisfactory to good. Agreement (Spearman rho) in total scores between parents
      was 0.65, between parent and teacher 0.43 and between two teachers in day-care
      0.81. The stability in parent's reports over 12 weeks was good. The distributions
      of the informant-rated scores indicated significant and clinically important
      gender differences, and the 80th and 90th percentiles were generally below the
      international cut-off points. Public health nurses reported emotional or
      behavioural difficulties more commonly in non-participants (12%) than in
      participants (7%; p < 0.001). CONCLUSIONS: The results supported earlier findings
      of good internal consistency, inter-rater and cross-informant agreements and test
      retest of the method. However, the gender and age of the child, the number of
      informants and cultural differences in reporting styles affected the results and
      thus confirmed the need to re-evaluate the SDQ in the culture and population in
      question.

PMID- 22397525
TI  - Intramuscular injection of paraquat for suicidal attempt: a rare case report.

PMID- 22397526
TI  - Facile synthesis of few-layer graphene with a controllable thickness using rapid
      thermal annealing.
AB  - Few-layer graphene films with a controllable thickness were grown on a nickel
      surface by rapid thermal annealing (RTA) under vacuum. The instability of nickel
      films in air facilitates the spontaneous formation of ultrathin (<2-3 nm) carbon-
      and oxygen-containing compounds on a nickel surface; thus, the high-temperature
      annealing of the nickel samples without the introduction of intentional carbon
      containing precursors results in the formation of graphene films. From annealing
      temperature and ambient studies during RTA, it was found that the evaporation of
      oxygen atoms from the surface is the dominant factor affecting the formation of
      graphene films. The thickness of the graphene layers is strongly dependent on the
      RTA temperature and time, and the resulting films have a limited thickness (<2
      nm), even for an extended RTA time. The transferred films have a low sheet
      resistance of ~0.9 +/- 0.4 kOmega/sq, with ~94% +/- 2% optical transparency,
      making them useful for applications as flexible transparent conductors.

PMID- 22397528
TI  - Long-term biochemical results after high-dose-rate intensity modulated
      brachytherapy with external beam radiotherapy for high risk prostate cancer.
AB  - BACKGROUND: Biochemical control from series in which radical prostatectomy is
      performed for patients with unfavorable prostate cancer and/or low dose external
      beam radiation therapy are given remains suboptimal.The treatment regimen of HDR
      brachytherapy and external beam radiotherapy is a safe and very effective
      treatment for patients with high risk localized prostate cancer with excellent
      biochemical control and low toxicity.

PMID- 22397529
TI  - Type D personality, physical symptoms and subjective stress: the mediating
      effects of coping and social support.
AB  - Coping style and social support may represent mechanisms to explain the
      relationship between Type D personality and ill-health. This study investigated
      whether Type D is associated with physical symptoms and perceived stress in a non
      cardiac population, and if these relationships are mediated by coping and social
      support. In a cross-sectional study, 304 participants (110 males, mean age 22.1
      years) completed measures of Type D, physical symptoms, coping, perceived stress
      and social support. Results showed that Type D, the interaction of negative
      affectivity and social inhibition (NA * SI), was positively correlated with
      physical symptoms, perceived stress, and avoidant coping, and negatively
      correlated with social support, problem-focused coping and emotion-focused
      coping. A series of bootstrapped multiple mediator tests showed that social
      support and avoidant coping fully mediated the relationship between Type D and
      physical symptoms. Furthermore, social support and emotion-focused coping
      partially mediated the relationship between Type D and perceived stress. These
      findings demonstrate for the first time that Type D personality is associated
      with physical symptoms in a non-cardiac population. Social support and coping
      style represent mechanisms that can, in part, explain the relationship between
      Type D and physical symptoms, and Type D and perceived stress.

PMID- 22397530
TI  - Medical emergencies on board commercial airlines: is documentation as expected?
AB  - INTRODUCTION: The purpose of this study was to perform a descriptive, content
      based analysis on the different forms of documentation for in-flight medical
      emergencies that are currently provided in the emergency medical kits on board
      commercial airlines. METHODS: Passenger airlines in the World Airline Directory
      were contacted between March and May 2011. For each participating airline, sample
      in-flight medical emergency documentation forms were obtained. All items in the
      sample documentation forms were subjected to a descriptive analysis and compared
      to a sample "medical incident report" form published by the International Air
      Transport Association (IATA). RESULTS: A total of 1,318 airlines were contacted.
      Ten airlines agreed to participate in the study and provided a copy of their
      documentation forms. A descriptive analysis revealed a total of 199 different
      items, which were summarized into five sub-categories: non-medical data (63),
      signs and symptoms (68), diagnosis (26), treatment (22) and outcome (20).
      CONCLUSIONS: The data in this study illustrate a large variation in the
      documentation of in-flight medical emergencies by different airlines. A higher
      degree of standardization is preferable to increase the data quality in
      epidemiologic aeromedical research in the future.

PMID- 22397531
TI  - AtPAN: an integrated system for reconstructing transcriptional regulatory
      networks in Arabidopsis thaliana.
AB  - BACKGROUND: Construction of transcriptional regulatory networks (TRNs) is of
      priority concern in systems biology. Numerous high-throughput approaches,
      including microarray and next-generation sequencing, are extensively adopted to
      examine transcriptional expression patterns on the whole-genome scale; those data
      are helpful in reconstructing TRNs. Identifying transcription factor binding
      sites (TFBSs) in a gene promoter is the initial step in elucidating the
      transcriptional regulation mechanism. Since transcription factors usually co
      regulate a common group of genes by forming regulatory modules with similar
      TFBSs. Therefore, the combinatorial interactions of transcription factors must be
      modeled to reconstruct the gene regulatory networks. Description For systems
      biology applications, this work develops a novel database called Arabidopsis
      thaliana Promoter Analysis Net (AtPAN), capable of detecting TFBSs and their
      corresponding transcription factors (TFs) in a promoter or a set of promoters in
      Arabidopsis. For further analysis, according to the microarray expression data
      and literature, the co-expressed TFs and their target genes can be retrieved from
      AtPAN. Additionally, proteins interacting with the co-expressed TFs are also
      incorporated to reconstruct co-expressed TRNs. Moreover, combinatorial TFs can be
      detected by the frequency of TFBSs co-occurrence in a group of gene promoters. In
      addition, TFBSs in the conserved regions between the two input sequences or
      homologous genes in Arabidopsis and rice are also provided in AtPAN. The output
      results also suggest conducting wet experiments in the future. CONCLUSIONS: The
      AtPAN, which has a user-friendly input/output interface and provide graphical
      view of the TRNs. This novel and creative resource is freely available online at
      http://AtPAN.itps.ncku.edu.tw/.

PMID- 22397532
TI  - Polar switching in trialkylbenzene-1,3,5-tricarboxamides.
AB  - The hydrogen-bonded hexagonal columnar LC (Col(hd)) phases formed by benzene
      1,3,5-tricarboxamide (BTA) derivatives can be aligned uniformly by an electric
      field and display switching behavior with a high remnant polarization. The polar
      switching in three symmetrically substituted BTAs with alkyl chains varying in
      length between 6 and 18 carbon atoms (C6, C10, and C18) was investigated by
      electro-optical switching experiments, dielectric relaxation spectroscopy (DRS),
      and solid-state NMR. The goal was to characterize ferroelectric properties of BTA
      based columnar LCs, which display a macroscopic axial dipole moment due to the
      head-to-tail stacking of hydrogen-bonded amides. The Col(hd) phase of all three
      BTAs can be aligned uniformly by a dc field ~30 V/MUm. Moreover, C10 and C18
      display extrinsic polar switching characterized by a remnant polarization and
      coercive field of 1-2 MUC/cm(2) and 20-30 V/MUm, respectively. In the absence of
      an external field, the polarization is lost in 1-1000 s, depending on device
      details and temperature. DRS revealed a columnar glass transition in the low
      temperature region of the LC phase related to collective vibrations in the
      hydrogen-bonded columns that freeze out below 41-54  degrees C. At higher
      temperatures, a relaxation process is present originating from the collective
      reorientation of amide groups along the column axis (inversion of the
      macrodipole). Matching activation energies suggest that the molecular mechanism
      underlying the polar switching and the R-processes is identical. These results
      illustrate that LC phases based on BTAs offer the unique possibility to integrate
      polarization with other functionalities in a single nanostructured material.

PMID- 22397533
TI  - Genotoxicity of multi-walled carbon nanotubes in both in vitro and in vivo assay
      systems.
AB  - The genotoxic effects of multi-walled carbon nanotubes (MWCNTs) were examined by
      using in vitro and in vivo assays. MWCNTs significantly induced micronuclei in
      A549 cells and enhanced the frequency of sister chromatid exchange (SCE) in CHO
      AA8 cells. When ICR mice were intratracheally instilled with a single dose (0.05
      or 0.2 mg/animal) of MWCNTs, DNA damage of the lungs, analysed by comet assay,
      increased in a dose-dependent manner. Moreover, DNA oxidative damage, indicated
      by 8-oxo-7,8-dihydro-2'-deoxyguanosine and heptanone etheno-deoxyribonucleosides,
      occurred in the lungs of MWCNT-exposed mice. The gpt mutation frequencies
      significantly increased in the lungs of MWCNT-treated gpt delta transgenic mice.
      Transversions were predominant, and G:C to C:G was clearly increased by MWCNTs.
      Moreover, many regions immunohistochemically stained for inducible NO synthase
      and nitrotyrosine were observed in the lungs of MWCNT-exposed mice. Overall,
      MWCNTs were shown to be genotoxic both in in vitro and in vivo tests; the
      mechanisms probably involve oxidative stress and inflammatory responses.

PMID- 22397534
TI  - "More simply human than otherwise" Harry S. Sullivan's "Conceptions of modern
      psychiatry" the first William Alanson White Memorial Lectures (Published 1940).

PMID- 22397535
TI  - Conceptions of modern psychiatry: the first William Alanson White Memorial
      Lectures. 1940.

PMID- 22397536
TI  - Commentary on "Conceptions of modern psychiatry": in pursuit of emotional
      security.

PMID- 22397537
TI  - Commentary on "Conceptions of modern psychiatry": humanism as an aspect of
      psychiatry and psychiatrists: where are we and where are we headed?

PMID- 22397538
TI  - Commentary on "Conceptions of modern psychiatry": Sullivan and his polarizing
      legacy.

PMID- 22397539
TI  - Commentary on "Conceptions of modern psychiatry": from attachment to
      intersubjectivity.
AB  - I am honored and humbled by the invitation to comment on the wisdom of a true
      giant in the history of psychiatry, Harry Stack Sullivan. Resonating with the
      prescience of his thought as any contemporary reader would, I am astonished by
      its pertinence to current concerns. Four domains of resonance strike me: the role
      of neurobiology in psychiatry, the social origins of mind in attachment
      relationships, the contribution of self-hate to suicide and, perhaps most
      important for clinicians, the intersubjective process of diagnostic understanding
      and treatment. As an expression of admiration for the timelessness of Sullivan's
      essay and appreciation for all we have learned from him, my comments merely
      explicate how some of his thoughts are playing out in contemporary theory and
      research.

PMID- 22397540
TI  - Addressing therapeutic boundaries in social networking.
AB  - Facebook is the leading social networking website, with over 500 million users.
      Prior studies have shown an increasing number of housestaff accessing the site.
      While Facebook can be used to foster camaraderie, it can also create difficulties
      in the doctor-patient relationship, especially when boundaries are crossed. This
      study explored the prevalence of such boundary crossings and offers
      recommendations for training. An anonymous voluntary survey regarding Facebook
      use was distributed to current psychiatry residents through the American
      Psychiatric Association (APA) listserv. Of the 182 respondents, 95.7% had current
      Facebook profiles, and 9.7% had received friend requests from patients. In
      addition, 18.7% admitted to viewing patient profiles on Facebook. There is a
      substantial utilization of Facebook among psychiatric residents as compared with
      prior studies. Specific guidance regarding social media websites and the
      potential for ethical difficulties should be offered to trainees.

PMID- 22397541
TI  - Leadership, cohesion, morale, and the mental health of UK Armed Forces in
      Afghanistan.
AB  - UK Armed Forces (AF) personnel deployed to Afghanistan are frequently exposed to
      intense combat and yet little is known about the short-term mental health
      consequences of this exposure and the potential mitigating effects of military
      factors such as cohesion, morale, and leadership. To assess the possible
      modulating influence of cohesion, morale, and leadership on post-traumatic stress
      disorder (PTSD) symptoms and common mental disorders resulting from combat
      exposure among UK AF personnel deployed to Afghanistan, UK AF personnel, during
      their deployment to Afghanistan in 2010, completed a self-report survey about
      aspects of their current deployment, including perceived levels of cohesion,
      morale, leadership, combat exposure, and their mental health status. Outcomes
      were symptoms of common mental disorder and symptoms of PTSD. Combat exposure was
      associated with both PTSD symptoms and symptoms of common mental disorder. Of the
      1,431 participants, 17.1% reported caseness levels of common mental disorder, and
      2.7% were classified as probable PTSD cases. Greater self-reported levels of unit
      cohesion, morale, and perceived good leadership were all associated with lower
      levels of common mental disorder and PTSD. Greater levels of unit cohesion,
      morale, and good leadership may help to modulate the effects of combat exposure
      and the subsequent development of mental health problems among UK Armed Forces
      personnel deployed to Afghanistan.

PMID- 22397542
TI  - Can people remain engaged and vigorous in the face of trauma? Palestinians in the
      West Bank and Gaza.
AB  - This is the first study to investigate how actively engaged and vigorous people
      remain in their life tasks in the midst of chronic exposure to significant
      traumatic events. We sought to identify risk and protective factors for
      engagement within the context of ongoing exposure to political violence and
      social upheaval. We randomly identified and interviewed 1,196 adult residents of
      the West Bank and Gaza during a period of violent conflict on 3 occasions: (1)
      September-October 2007, (2) April-May 2008, and (3) October-November 2008.
      Participants were asked about their exposure to political violence, symptoms of
      depression, and posttraumatic stress (PTS) symptoms, their level of social
      support, psychosocial resource loss, and positive engagement in life tasks. Path
      modeling revealed that trauma exposure indirectly affected engagement through its
      impact on resource loss and PTS and depression symptoms. PTS symptoms at Wave 2
      were modestly related to greater engagement at Wave 3, and depression symptoms
      did not independently predict engagement at Wave 3. Psychosocial resource loss at
      Wave 1 and Wave 2 was the best overall predictor of engagement at Wave 3, through
      its direct and indirect effects via PTS symptoms. Greater engagement was also
      predicted by greater social support, being more educated, being younger, and
      being more religious. The relative independence of psychological distress and
      engagement was noted as a critical finding supporting a key tenet of positive
      psychology. The relationship of resource loss and social support with engagement
      suggests that bolstering psychosocial resources may offer a route for primary and
      secondary prevention amidst chronic traumatic conditions.

PMID- 22397543
TI  - Bereavement and mental health after sudden and violent losses: a review.
AB  - This paper reviews the literature on the psychological consequences of sudden and
      violent losses, including disaster and military losses. It also reviews risk and
      resilience factors for grief and mental health and describes the effects and
      possible benefit of psychosocial interventions. The review shows gaps in the
      literature on grief and bereavement after sudden and violent deaths. Still, some
      preliminary conclusions can be made. Several studies show that a sudden and
      violent loss of a loved one can adversely affect mental health and grief in a
      substantial number of the bereaved. The prevalence of mental disorders such as
      post-traumatic stress disorder (PTSD), major depressive disorder (MDD), and
      prolonged grief disorder (PGD, also termed complicated grief) varies widely,
      however, from study to study. Also, mental health disorders are more elevated
      after sudden and violent losses than losses following natural deaths, and the
      trajectory of recovery seems to be slower. Several factors related to the
      circumstances of the loss may put the bereaved at heightened risk for mental
      distress. These factors may be differentially related to different outcomes; some
      increase the risk for PTSD, others for PGD. Given the special circumstances,
      bereavement following sudden and violent death may require different
      interventions than for loss from natural death. Recommendations for future
      research and clinical implications are discussed.

PMID- 22397545
TI  - Quantitative determination of PAHs in biochar: a prerequisite to ensure its
      quality and safe application.
AB  - Biochar is increasingly promoted as a beneficial soil conditioner. However, it
      may contain residues of polycyclic aromatic hydrocarbons (PAHs) as a result of
      its production by pyrolysis. To date, analytical methods to analyze PAHs in
      biochar quantitatively are hardly available. This study presents an optimized and
      validated procedure to quantify the 16 U.S. EPA PAHs in biochar. PAHs were best
      extracted with Soxhlet for 36 h using 100% toluene. Average absolute recoveries
      of isotope labeled internal standards used for each analyte from three different
      biochars ranged from 42% to 72%, and relative recoveries were between 71% and
      105%. The limits of detection were biochar-dependent, but on average a factor of
      >50 lower than quantified PAH concentrations (9-355 mg kg(dry weight)(-1)). The
      established method prepares the ground for a harmonized protocol for PAH analysis
      of biochars, a necessity for biochar quality control, registration, and
      legislation.

PMID- 22397546
TI  - Environmental occurrence and distribution of short chain chlorinated paraffins in
      sediments and soils from the Liaohe River Basin, P. R. China.
AB  - Chlorinated paraffins (CPs) are industrially produced in large quantities in the
      Liaohe River Basin. Their discharge inevitably causes environmental
      contamination. However, very limited information is available on their
      environmental levels and distributions in this typical industrial region. In this
      study, short chain CPs (SCCPs) were analyzed in sediments, paddy soils, and
      upland soils from the Liaohe River Basin, with concentrations ranging from 39.8
      to 480.3 ng/g dry weight. A decreasing trend in SCCP concentrations was found
      with increasing distance from the cities, suggesting that local industrial
      activity was the major source of SCCP contamination. A preliminary sediment
      inventory of SCCPs indicated approximately 30.82 tonnes of SCCPs residual in the
      sediments from the Liaohe River. The average discharge of SCCPs was estimated to
      be about 74.4 mg/tonne industrial wastewater. The congener group profiles showed
      that the relative abundances of shorter chain and lower chlorinated CP congeners
      (C(10)-CPs with 5 or 6 chlorine atoms) in soils in rural areas were higher than
      in sites near cities, which demonstrated that long-range atmospheric
      transportation could be the major transport pathway. Environmental degradation of
      SCCPs might occur, where higher chlorinated congeners could dechlorinate to form
      the lower chlorinated congeners.

PMID- 22397547
TI  - Determinants of emergency response willingness in the local public health
      workforce by jurisdictional and scenario patterns: a cross-sectional survey.
AB  - BACKGROUND: The all-hazards willingness to respond (WTR) of local public health
      personnel is critical to emergency preparedness. This study applied a threat-and
      efficacy-centered framework to characterize these workers' scenario and
      jurisdictional response willingness patterns toward a range of naturally
      occurring and terrorism-related emergency scenarios. METHODS: Eight
      geographically diverse local health department (LHD) clusters (four urban and
      four rural) across the U.S. were recruited and administered an online survey
      about response willingness and related attitudes/beliefs toward four different
      public health emergency scenarios between April 2009 and June 2010 (66% response
      rate). Responses were dichotomized and analyzed using generalized linear
      multilevel mixed model analyses that also account for within-cluster and within
      LHD correlations. RESULTS: Comparisons of rural to urban LHD workers showed
      statistically significant odds ratios (ORs) for WTR context across scenarios
      ranging from 1.5 to 2.4. When employees over 40 years old were compared to their
      younger counterparts, the ORs of WTR ranged from 1.27 to 1.58, and when females
      were compared to males, the ORs of WTR ranged from 0.57 to 0.61. Across the eight
      clusters, the percentage of workers indicating they would be unwilling to respond
      regardless of severity ranged from 14-28% for a weather event; 9-27% for pandemic
      influenza; 30-56% for a radiological 'dirty' bomb event; and 22-48% for an
      inhalational anthrax bioterrorism event. Efficacy was consistently identified as
      an important independent predictor of WTR. CONCLUSIONS: Response willingness
      deficits in the local public health workforce pose a threat to all-hazards
      response capacity and health security. Local public health agencies and their
      stakeholders may incorporate key findings, including identified scenario-based
      willingness gaps and the importance of efficacy, as targets of preparedness
      curriculum development efforts and policies for enhancing response willingness.
      Reasons for an increased willingness in rural cohorts compared to urban cohorts
      should be further investigated in order to understand and develop methods for
      improving their overall response.

PMID- 22397548
TI  - Engineering biogenic magnetite for sustained Cr(VI) remediation in flow-through
      systems.
AB  - In this work, we report a route to enhance the reactivity and longevity of
      biogenic magnetite in Cr(VI) remediation under continuous-flow conditions by
      combining functionalization of the biomagnetite surface with a precious metal
      catalyst, nanoscale palladium, and exposure to formate. Column influent
      conditions were varied to simulate oxic, anoxic, and nitrate cocontaminated
      environments. The addition of sodium formate as an electron donor for Pd
      functionalized magnetite increased capacity and longevity allowing 80% removal of
      Cr(VI) after 300 h in anoxic conditions, whereas complete breakthrough occurred
      after 60 h in anoxic nonformate and nonfunctionalized systems. Removal of Cr(VI)
      was optimized under anoxic conditions, and the presence of oxidizing agents
      results in a modest loss in reductive capacity. Examination of reacted Pd
      functionalized magnetite reveals close association of Fe with Cr, suggesting that
      Pd-coupled oxidation of formate serves to regenerate the reactive surface. XMCD
      studies revealed that Cr(III) is partially substituted for Fe in the magnetite
      structure, which serves to immobilize Cr. No evidence for a mechanistic
      interference by nitrate cocontamination was observed, suggesting that this novel
      system could provide robust, effective and sustained reduction of contaminants,
      even in the presence of common oxidizing cocontaminants, outperforming the
      reductive capacity of nonfunctionalized biogenic magnetite.

PMID- 22397549
TI  - Delocalization-to-localization charge transition in diferrocenyl-oligothienylene
      vinylene molecular wires as a function of the size by Raman spectroscopy.
AB  - In going from short to large size thienylene-vinylene diferrocenyl cations, the
      transition from a charge delocalized to a localized state is addressed by
      resonance Raman spectroscopy and supported by theoretical model chemistry. The
      shorter members, dimer and tetramer, display conjugated structures near the
      cyanine limit of bond length equalization as a result of the strong
      interferrocene charge resonance, producing a full charge delocalized mixed
      valence system. In the longest octamer, charge resonance vanishes and the cation
      is localized at the bridge center (the mixed valence property disappears). The
      hexamer is at the delocalized-to-localized turning point. Solvent and variable
      temperature Raman measurements highlight this borderline property. A detailed
      structure-property correlation of bond length alternation data and Raman
      frequencies is proposed to account for the whole set of spectroscopic properties,
      with emphasis on the changes observed with the size of the molecular wire.

PMID- 22397550
TI  - Galactose decorated PLGA nanoparticles for hepatic delivery of acyclovir.
AB  - The present study explores prospective of surface tailored nanoparticles for
      targeted delivery of acyclovir along with the interception of minimal side
      effects. Acyclovir loaded plain and galactosylated poly lectic co glycolic acid
      (PLGA) nanoparticles were efficiently prepared and characterized by Fourier
      transform infrared spectroscopy, scanning electron microscopy (SEM), size,
      polydispersity index, zeta potential, and entrapment efficiency. The formulations
      were evaluated for in vitro drug release and hemolysis. Further, biodistribution
      study and fluorescent microscopic studies were carried out to determine the
      targeting potential of formulations. SEM revealed smooth morphology and spherical
      shape of the nanoparticles. In vitro, the galactosylated nanoparticles were found
      to be least hemolytic and exhibited a sustained release pattern. In vivo studies
      exhibited an augmented bioavailability, increased residence time and enhanced
      delivery of acyclovir to the liver upon galactosylation. It may therefore be
      concluded that galactose conjugated PLGA nanoparticles can be used suitably as
      vehicles for delivery of bioactives specifically to the hepatic tissues and may
      be thus exploited in the effective management of various liver disorders. 

PMID- 22397551
TI  - Facile preparation of zwitterionic organic-silica hybrid monolithic capillary
      column with an improved "one-pot" approach for hydrophilic-interaction liquid
      chromatography (HILIC).
AB  - A simple single-step thermal-treatment "one-pot" approach for the preparation of
      organic-silica hybrid capillary monolithic columns is described. In this improved
      method, the cross-linker vinyltrimethoxysilane (VTMS) was replaced by 3
      methacryloxypropyltrimethoxysilane (gamma-MAPS), which is more active in
      polymerization reactions, and only one thermal treatment step was required in the
      preparation of hybrid monoliths. Two zwitterionic organic-silica monolithic
      columns were successfully synthesized by using [2-(methacryloyloxy)ethyl]dimethyl
      (3-sulfopropyl)ammonium hydroxide (MSA) and 2-methacryloyloxyethyl
      phosphorylcholine (MPC) as the organic monomers. The effects of the
      tetramethoxysilane (TMOS)/gamma-MAPS molar ratio, content of monomer, composition
      of porogenic solvent, and reaction temperature on the morphologies of the hybrid
      monoliths were investigated. The MSA-silica and MPC-silica hybrid monolithic
      columns exhibited good permeability and good mechanical stability. The monolithic
      columns were used for the separation of polar compounds by capillary hydrophilic
      interaction chromatography (cHILIC). A typical HILIC retention mechanism was
      observed at higher organic solvent contents (>50% ACN). The MSA monoliths were
      further investigated in the separation of various neutral, basic, and acidic
      analytes, as well as small peptides, by capillary liquid chromatography (cLC),
      and high efficiency and satisfactory reproducibility were achieved. In addition,
      the analysis of a tryptic digest of bovine serum albumin (BSA) by cLC tandem mass
      spectrometry (cLC-MS/MS) with an MSA monolith further demonstrated its potential
      in the separation of biological samples.

PMID- 22397552
TI  - Protection of ceruloplasmin by lactoferrin against hydroxyl radicals is pH
      dependent.
AB  - Destruction of ceruloplasmin (Cp) in the presence of hydrogen peroxide is
      accompanied by the release of the protein's copper ions that provoke formation of
      hydroxyl radicals (OH) and, consequently, further degradation of the protein.
      Under such conditions, degradation of Cp is hampered by a number of substances
      able to bind copper ions. Lactoferrin (Lf) is the most active protector of Cp,
      its protective effect depending on the pH of the medium. The best protection of
      Cp by Lf was detected at pH 7.4. In an acidic buffer (pH 5.5), Lf did not affect
      the destruction of Cp. The pH-dependent efficiency of copper binding by Lf is in
      good agreement with its capacity to protect Cp against degradation provoked by
      hydrogen peroxide. It seems likely that peroxide-dependent degradation of Cp
      stimulated by its own copper ions is a part of neutrophil-induced antimicrobial
      reactions and may take place properly at the foci of inflammation. Interaction of
      Lf with Cp may regulate the generation of OH from hydrogen peroxide in the foci
      of inflammation and protect the adjacent tissues.

PMID- 22397553
TI  - Osteoblastoma of the rib with CT and MR imaging: a case report and literature
      review.
AB  - Osteoblastoma is a rare bone tumor which is mostly found in the vertebral column
      and long bone. We describe a 59-year-old woman with osteoblastoma in the right
      fifth posterior segment of the rib, whose presenting symptoms were right back
      pain for two years and awakened at night. Chest computer tomography (CT) and
      thoracic spine magnetic resonance (MR) imaging findings included an expansile
      lesion of the right fifth rib and an ossified matrix. Surgical resection of the
      lesion confirmed a benign osteoblastoma. 12 months follow-up revealed
      disappearance of right back pain. Rib osteoblastoma in plain film has been
      described previously; however, to our knowledge this is the only case report
      emphasized in CT and MR imaging.

PMID- 22397554
TI  - Immunomodulation and infection: back to the future.

PMID- 22397555
TI  - Immune modulatory strategies: a playground with a swing and a seesaw.

PMID- 22397556
TI  - The role of T cells in the pathogenesis of classical Whipple's disease.

PMID- 22397557
TI  - Host genetics and invasive fungal diseases: towards improved diagnosis and
      therapy?

PMID- 22397558
TI  - Targets for immunochemotherapy in leishmaniasis.

PMID- 22397560
TI  - Boceprevir: an oral protease inhibitor for the treatment of chronic HCV
      infection.
AB  - Chronic hepatitis C (CHC) virus infection affects more than 170 million people
      globally. The aim of treatment of CHC is to affect sustained elimination of the
      virus (a sustained virological response [SVR]). The success and duration of
      therapy with interferon is dependent on HCV genotype. The current standard of
      care comprises combined treatment with pegylated interferon and ribavirin. Rates
      of SVR in patients with genotype 1 infection, the least responsive group, are
      less than 50%. Boceprevir is a ketoamide protease inhibitor that binds reversibly
      to the HCV nonstructural NS3 protease active site inhibiting intracellular viral
      replication. Phase III clinical studies have demonstrated that, in combination
      with the current standard of care, boceprevir significantly increases the SVR
      rate in both treatment-naive and previously treated patients with genotype 1 CHC.
      Both the US FDA and EMA have approved boceprevir for the treatment of genotype 1
      CHC: the first directly-acting antiviral drug to be licensed for this indication.
      This article will review the pharmacology and pharmacodynamics of boceprevir, the
      efficacy and safety of the drug, and explore possible future developments in the
      management of CHC.

PMID- 22397561
TI  - Pulmonary innate lymphoid cells regulate repair and remodeling after acute lung
      injury.
AB  - The restoration of lung-tissue architecture and a return to a homeostatic state
      following injury or inflammation is critical to effective pulmonary function.
      This article assesses the findings of a recently published study by Monticelli et
      al. in Nature Immunology that describes a novel population of innate lymphoid
      cells in the lungs of mice and humans, with a critical role in restoring
      epithelial airway integrity following influenza infection. The significance of
      this study in the context of our current knowledge of innate lymphoid cells, and
      its implications and potential for therapeutic manipulation, shall be evaluated
      within this article.

PMID- 22397562
TI  - Upregulation of MHC class I expression following dengue virus infection: the
      mechanism at the promoter level.
AB  - Unlike many other viruses that downregulate MHC class I expression on infected
      cell membranes, flaviviruses were reported to upregulate the MHC class I
      expression. Dengue virus was shown to induce HLA class I expression; however, the
      precise transcriptional mechanism that is used by the virus remains unclear. This
      article assessed the findings of a recently published report describing the
      mechanism used by dengue virus to induce HLA-A2 expression and characterizing the
      transcription factors that are involved. The study showed that p50/p65 and p65/65
      NF-kappaB dimers bind to the class I regulatory complex within the HLA-A2
      promoter. This finding and its significance for the design of possible antiviral
      therapeutic agents are discussed in this article.

PMID- 22397563
TI  - The neonatal immune system: immunomodulation of infections in early life.
AB  - The innate and adaptive immune responses in neonates are usually functionally
      impaired when compared with their adult counterparts. The qualitative and
      quantitative differences in the neonatal immune response put them at risk for the
      development of bacterial and viral infections, resulting in increased mortality.
      Newborns often exhibit decreased production of Th1-polarizing cytokines and are
      biased toward Th2-type responses. Studies aimed at understanding the plasticity
      of the immune response in the neonatal and early infant periods or that seek to
      improve neonatal innate immune function with adjuvants or special formulations
      are crucial for preventing the infectious disease burden in this susceptible
      group. Considerable studies focused on identifying potential immunomodulatory
      therapies have been performed in murine models. This article highlights the
      strategies used in the emerging field of immunomodulation in bacterial and viral
      pathogens, focusing on preclinical studies carried out in animal models with
      particular emphasis on neonatal-specific immune deficits.

PMID- 22397564
TI  - Can an immune-regulatory vaccine prevent HIV infection?
AB  - Developing vaccines to prevent the establishment of HIV infection has been
      fraught with difficulties. It might therefore be important to consider other new
      strategies. Since several studies suggest that anti-inflammatory stimuli can
      protect from HIV infection and because HIV replicates preferably in activated T
      cells, we suggest here that the reduction of immune activation through a HIV
      specific regulatory T-cell vaccine might thwart early viral replication. Thus,
      because immune activation is a good predictor of disease progression and the
      immune activation set point has been shown to be an early event during HIV
      infection, vaccinating to achieve control of early virus-specific immune
      activation might be advantageous.

PMID- 22397566
TI  - Immunomodulatory effects of antimicrobial agents. Part I: antibacterial and
      antiviral agents.
AB  - Despite impressive therapeutic progresses in the battle against infections,
      microorganisms are still a threat to mankind. With hundreds of antibacterial
      molecules, major concerns remain about the emergence of resistant and multidrug
      resistant pathogens. On the other hand, the antiviral drug armamentarium is
      comprised of only a few dozens of compounds which are highly pathogen specific,
      and resistance is also a concern. According to Arturo Casadevall (Albert Einstein
      College of Medicine, NY, USA), we have now entered the third era of anti
      infective strategy, which intends to favor the interplay between active molecules
      and the immune system. The first part of this review focuses on the potential
      immunomodulating properties of anti-infective agents, beginning with
      antibacterial and antiviral agents.

PMID- 22397567
TI  - Immunomodulatory effects of antimicrobial agents. Part II: antiparasitic and
      antifungal agents.
AB  - Antiparasitic and antifungal drugs have not received the same high level of
      recognition as antimicrobial drugs. They are comparatively few in number, the
      great majority of them were developed more than a century ago, they have many
      adverse side effects and are subject to the emergence of drug resistance. The
      second part of the review, devoted to the immunomodulatory effects of
      antimicrobial agents, addresses the interference of antiparasitic and antifungal
      agents with the host natural defenses and the deleterious or beneficial
      consequences of these properties.

PMID- 22397565
TI  - Could immunomodulation be used to prevent prion diseases?
AB  - All prion diseases are currently without effective treatment and are universally
      fatal. The underlying pathogenesis of prion diseases (prionoses) is related to an
      autocatalytic conformational conversion of PrP(C) (C for cellular) to a
      pathological and infectious conformer known as PrP(Sc) (Sc for scrapie) or
      PrP(Res) (Res for proteinase K resistant). The past experience with variant
      Creutzfeldt-Jakob disease, which originated from bovine spongiform
      encephalopathy, as well as the ongoing epidemic of chronic wasting disease has
      highlighted the necessity for effective prophylactic and/or therapeutic
      approaches. Human prionoses are most commonly sporadic, and hence therapy is
      primarily directed to stop progression; however, in animals the majority of
      prionoses are infectious and, as a result, the emphasis is on prevention of
      transmission. These infectious prionoses are most commonly acquired via the
      alimentary tract as a major portal of infectious agent entry, making mucosal
      immunization a potentially attractive method to produce a local immune response
      that can partially or completely prevent prion entry across the gut barrier,
      while at the same time producing a modulated systemic immunity that is unlikely
      to be associated with toxicity. A critical factor in any immunomodulatory
      methodology that targets a self-antigen is the need to delicately balance an
      effective humoral immune response with potential autoimmune inflammatory
      toxicity. The ongoing epidemic of chronic wasting disease affecting the USA and
      Korea, with the potential to spread to human populations, highlights the need for
      such immunomodulatory approaches.

PMID- 22397568
TI  - Therapeutic modulation of miRNA for the treatment of proinflammatory lung
      diseases.
AB  - miRNAs are short, nonprotein coding RNAs that regulate target gene expression
      principally by causing translational repression and/or mRNA degradation. miRNAs
      are involved in most mammalian biological processes and have pivotal roles in
      controlling the expression of factors involved in basal and stimulus-induced
      signaling pathways. Considering their central role in the regulation of gene
      expression, miRNAs represent therapeutic drug targets. Here we describe how
      miRNAs are involved in the regulation of aspects of innate immunity and
      inflammation, what happens when this goes awry, such as in the chronic
      inflammatory lung diseases cystic fibrosis and asthma, and discuss the current
      state-of-the-art miRNA-targeted therapeutics.

PMID- 22397569
TI  - The immune response to severe bacterial infections: consequences for therapy.
AB  - The immune response to a bacterial stimulus starts when pathogen-associated
      molecular patterns of the bacterial pathogens activate pattern recognition
      receptors of the innate immune system. This leads to production of
      proinflammatory and anti-inflammatory mediators aiming to contain infection and
      drive the clinical signs of sepsis. When sepsis and signs of failing organs are
      apparent, proinflammatory phenomena have ceased; a hypoinflammatory phase
      predominates, characterized by anergy of monocytes and apoptosis of T
      lymphocytes. The above sequence of events seems to differ from one patient to the
      next. The majority of therapies targeting the immune responses have failed to
      provide clinical benefit. Immunostimulation with IFN-gamma and leukocyte growth
      factors, hemoperfusion with polymyxin B-embedded fiber column, and macrolides
      remain the most promising immunomodulators in clinical practice.

PMID- 22397570
TI  - Immune approaches in tuberculosis therapy: a brief overview.
AB  - TB is typically caused by Mycobacterium tuberculosis, a symbiotic bacterium
      present in one-third of the world's population. There any many factors triggering
      overt clinical disease in a small proportion of humans. In our view the major
      role in the process is played by the host's immune response, especially self
      directed, destructive inflammation. Conventional chemotherapy produces
      bactericidal or bacteriostatic effects, but immunopathological changes can only
      be corrected by immunotherapy. Various attempts have been made to identify the
      optimal immune intervention. Some have shown promising effects, but many have
      failed. It is commonly believed that the field started in 1890: the year Robert
      Koch announced his tuberculin therapy. In the Pen Ts'ao Kang Mu, classical
      Chinese materia medica, published during Ming dynasty, Li Shi Chen (1518-1593)
      recommended, as a remedy for hemoptysis, to collect from the sputum "...blood
      lumps, roast them till they are black, and take then them as a powder". In
      retrospect, this is perhaps the earliest recorded reference relating to
      immunotherapy of TB with heat-killed mycobacteria. Modern science is obviously
      geared toward more palatable approach, but without hindsight from often disdained
      empirical evidence no progress can be made. The clinical experience from various
      trial and error processes is briefly discussed in this review.

PMID- 22397572
TI  - A rare case of small bowel volvulus after jenjunoileal bariatric bypass requiring
      emergency surgery: a case report.
AB  - INTRODUCTION: Bariatric surgery is on the increase throughout the world.
      Jejunoileal bypass bariatric procedures have fallen out of favor in western
      surgical centers due to the high rate of associated complications. They are,
      however, performed routinely in other centers and as a consequence of health
      tourism, management of complications related to these procedures may still be
      encountered. CASE PRESENTATION: We describe a rare case of small bowel
      obstruction in a 45-year-old British Caucasian woman, secondary to a volvulus of
      the jejunoileal anastomosis following bariatric bypass surgery. The pre-operative
      diagnosis was confirmed by radiology. We describe a successful surgical technique
      for this rare complication. CONCLUSIONS: Bariatric surgery may be complicated by
      bowel obstruction. Early imaging is vital for diagnosis and effective management.
      The use of our surgical technique provides a simple and effective approach for
      the successful management of this bariatric complication.

PMID- 22397571
TI  - Immunomodulation for gastrointestinal infections.
AB  - The intestinal epithelium provides a barrier between a variety of luminal
      antigens and provides the components of intestinal innate and adaptive immunity.
      It is crucial that at this interface, the epithelial cell layer and the
      components of the intestinal immunity interact with dietary and bacterial
      antigens in a regulated way to maintain homeostasis. Failure to tightly control
      immune reactions can be detrimental and result in inflammation. In the current
      review, we described the regulatory mechanisms controlling host-immune
      homeostasis and the role of regulatory CD4(+) T cells, with a special emphasis in
      the regulatory T-cell subsets (Tregs). Furthermore, the participation of innate
      cell cross-talk in the polarization of intestinal immune responses is also
      evaluated. Finally, the recent characterization of host responses to normal
      commensal flora, the role of bacteria and bacterial factors in the maintenance of
      immunomodulation, and the disruption of this balance by bacterial enteric
      pathogens is also summarized.

PMID- 22397575
TI  - Long-term follow-up of neonatally diagnosed primary megaureter: rate and
      predictors of spontaneous resolution.
AB  - OBJECTIVE: Primary megaureter (PM) represents 6-10% of all antenatal displaced
      urinary malformations. Spontaneous resolution of PM is a well-known event. This
      long-term follow-up study evaluated the incidence and rate of resolution of PM.
      Some predictive factors were revised, based on morphological classification and
      scintigraphic pattern. MATERIAL AND METHODS: Sixty neonates with PM were
      followed. The diagnosis was confirmed by ultrasound examination and (99m)Tc-DTPA
      diuretic renal scan. All the observed patients underwent antibiotic prophylaxis.
      All conservatively treated children were followed from 6 months to 15 years.
      Follow-up consisted of monthly urine cultures, renal ultrasound and DTPA diuretic
      renography. Hydroureteronephrosis was considered to have resolved when a
      retrovesical cross-sectional diameter of ureter less than 6 mm was found.
      RESULTS: In total, 72 PM were identified in this series. At the end of the follow
      up period, 38 PM (52.8%) had resolved, in 18 PM (25%) ureteral dilatation
      persisted and 16 PM (22.2%) required a surgical procedure. The median age at
      resolution was significantly affected by presenting hydronephrosis grade and
      cross-sectional diameter at diagnosis, but not by gender. The (99m)Tc-DTPA
      renogram results showed no functional impairment in resolved and persisting
      cases, even after long-term observation. CONCLUSIONS: The data show that 22% of
      neonatal PM require surgical treatment. Poor drainage on (99m)Tc-DTPA scan, grade
      IV-V hydronephrosis and ureteric diameter more than 15.0 mm were statistically
      significant and independent predictive factors for surgery. The time to
      spontaneous resolution in neonatally diagnosed PM may exceed 3.6 years, after
      which recovery is rare.

PMID- 22397574
TI  - The off-label treatment of severe hidradenitis suppurativa with TNF-alpha
      inhibitors: a systematic review.
AB  - To provide an overview of the current evidence regarding off-label treatment of
      hidradenitis suppurativa (HS) with TNF-alpha inhibitors, a systematic search was
      performed in MEDLINE, EMBASE and CENTRAL. Any type of original article concerning
      HS patients treated with infliximab, etanercept and/or adalimumab was included.
      No language restriction was applied. After full-text screening 65 studies
      involving 459 patients met the inclusion criteria and were subjected to data
      extraction. Four randomized controlled trials (RCTs) were available, and the
      remainders were case series or reports. Only RTCs were subjected to
      methodological quality assessment. Based on efficacy data extracted from the case
      reports, a moderate to good response was seen in 82% of the patients treated with
      infliximab, 76% of the patients treated with adalimumab, and 68% of the patients
      treated with etanercept. Due to the moderate level of evidence only a weak
      recommendation can be provided. If conventional treatment options fail, the use
      of TNF-alpha inhibitors can be a useful supplement for the treatment of recurrent
      severe HS. Infliximab should be preferred based on the most encouraging results
      regarding efficacy and expenses. Also adalimumab seems promising when
      administered in higher doses. The use of etanercept should be discouraged.

PMID- 22397573
TI  - An evaluation of oligonucleotide-based therapeutic strategies for polyQ diseases.
AB  - BACKGROUND: RNA interference (RNAi) and antisense strategies provide experimental
      therapeutic agents for numerous diseases, including polyglutamine (polyQ)
      disorders caused by CAG repeat expansion. We compared the potential of different
      oligonucleotide-based strategies for silencing the genes responsible for several
      polyQ diseases, including Huntington's disease and two spinocerebellar ataxias,
      type 1 and type 3. The strategies included nonallele-selective gene silencing,
      gene replacement, allele-selective SNP targeting and CAG repeat targeting.
      RESULTS: Using the patient-derived cell culture models of polyQ diseases, we
      tested various siRNAs, and antisense reagents and assessed their silencing
      efficiency and allele selectivity. We showed considerable allele discrimination
      by several SNP targeting siRNAs based on a weak G-G or G-U pairing with normal
      allele and strong G-C pairing with mutant allele at the site of RISC-induced
      cleavage. Among the CAG repeat targeting reagents the strongest allele
      discrimination is achieved by miRNA-like functioning reagents that bind to their
      targets and inhibit their translation without substantial target cleavage. Also,
      morpholino analog performs well in mutant and normal allele discrimination but
      its efficient delivery to cells at low effective concentration still remains a
      challenge. CONCLUSIONS: Using three cellular models of polyQ diseases and the
      same experimental setup we directly compared the performance of different
      oligonucleotide-based treatment strategies that are currently under development.
      Based on the results obtained by us and others we discussed the advantages and
      drawbacks of these strategies considering them from several different
      perspectives. The strategy aimed at nonallele-selective inhibiting of causative
      gene expression by targeting specific sequence of the implicated gene is the
      easiest to implement but relevant benefits are still uncertain. The gene
      replacement strategy that combines the nonallele-selective gene silencing with
      the expression of the exogenous normal allele is a logical extension of the
      former and it deserves to be explored further. Both allele-selective RNAi
      approaches challenge cellular RNA interference machinery to show its ability to
      discriminate between similar sequences differing in either single base
      substitutions or repeated sequence length. Although both approaches perform well
      in allele discrimination most of our efforts are focused on repeat targeting due
      to its potentially higher universality.

PMID- 22397576
TI  - Ovarian stimulation in women with high and normal body mass index: GnRH agonist
      versus GnRH antagonist.
AB  - In modern society, obesity has become a major health problem and has been
      associated with impaired fertility. The aim of this study is to assess the role
      of obesity in women undergoing controlled ovarian hyperstimulation (COH)
      stimulated either with GnRH agonists or with GnRH antagonists. Records of 463
      women undergoing in vitro fertilization (IVF) treatment were reviewed. The
      influence of body mass index (BMI) on treatment outcome was examined, after
      accounting for differences in stimulation protocols. In the agonist group (286
      patients), the total amount of gonadotropins used was significantly higher in
      patients with a BMI >= 25 kg/m2, when compared to those with a normal BMI. The
      same result was found in the antagonist group (177 patients). No significant
      differences were found in length of stimulation, number of oocytes retrieved or
      number of embryos transferred. In both the antagonist and the agonist group, the
      number of clinical pregnancies was found to be higher in patients with normal
      BMI, suggesting that obesity could impair the ovarian response to exogenous
      gonadotropins. Considering the results obtained and the many theoretical
      advantages of GnRH antagonists, ovarian stimulation with GnRH antagonists is an
      efficient treatment for both women with normal and high BMI.

PMID- 22397577
TI  - Simple liquid models with corrected dielectric constants.
AB  - Molecular simulations often use explicit-solvent models. Sometimes explicit
      solvent models can give inaccurate values for basic liquid properties, such as
      the density, heat capacity, and permittivity, as well as inaccurate values for
      molecular transfer free energies. Such errors have motivated the development of
      more complex solvents, such as polarizable models. We describe an alternative
      here. We give new fixed-charge models of solvents for molecular simulations-
      water, carbon tetrachloride, chloroform, and dichloromethane. Normally, such
      solvent models are parametrized to agree with experimental values of the neat
      liquid density and enthalpy of vaporization. Here, in addition to those
      properties, our parameters are chosen to give the correct dielectric constant. We
      find that these new parametrizations also happen to give better values for other
      properties, such as the self-diffusion coefficient. We believe that parametrizing
      fixed-charge solvent models to fit experimental dielectric constants may provide
      better and more efficient ways to treat solvents in computer simulations.

PMID- 22397578
TI  - The effect of dose rate on the frequency of specific-locus mutations induced in
      mouse spermatogonia is restricted to larger lesions; a retrospective analysis of
      historical data.
AB  - A series of 19 large-scale germ-cell mutagenesis experiments conducted several
      decades ago led to the conclusion that low-LET radiation delivered to mouse
      spermatogonia at dose rates of 0.8 R/min and below induced only about one-third
      as many specific-locus mutations as did single, acute exposures at 24 R/min and
      above. A two-hit origin of the mutations was deemed unlikely in view of the then
      prevailing evidence for the small size of genetic lesions in spermatogonia.
      Instead, the dose-rate effect was hypothesized to be the result of a repair
      system that exists in spermatogonia, but not in more mature male reproductive
      cells. More recent genetic and molecular studies on the marker genes have
      identified the phenotypes associated with specific states of the mutant
      chromosomes, and it is now possible retrospectively to classify individual past
      mutations as "large lesions" or "other lesions". The mutation-frequency
      difference between high and low dose rates is restricted to the large lesion
      mutations, for which the dose-curve slopes differ by a factor exceeding 3.4. For
      other lesion mutations, there is essentially no difference between the slopes for
      protracted and acute irradiations; induced other lesions frequencies per unit
      dose remain similar for dose rates ranging over more than 7 orders of magnitude.
      For large lesions, these values rise sharply at dose rates >0.8 R/min, though
      they remain similar within the whole range of protracted doses, failing to
      provide evidence for a threshold dose rate. The downward bend at high doses that
      had been noted for X-ray-induced specific-locus mutations as a whole and ascribed
      to a positive correlation between spermatogonial death and mutation load is now
      found to be restricted to large lesion mutations. There is a marked difference
      between the mutation spectra (distributions among the seven loci) for large
      lesions and other lesions. Within each class, however, the spectra are similar
      for acute and protracted irradiation.

PMID- 22397579
TI  - Investigations of La Rioja terroir for wine production using 1H NMR metabolomics.
AB  - In this study, La Rioja wine terroir was investigated by the use of (1)H NMR
      metabolomics on must and wine samples. Rioja is a small wine region in central
      northern Spain which can geographically be divided into three subareas (Rioja
      Alta, Rioja Baja, and Rioja Alavesa). The winemaking process from must, through
      alcoholic and malolactic fermentation, was followed by NMR metabolomics and
      chemometrics of nine wineries in the Rioja subareas (terroirs). Application of
      interval extended canonical variate analysis (iECVA) showed discriminative power
      between wineries which are geographically very close. Isopentanol and isobutanol
      compounds were found to be key biomarkers for this differentiation.

PMID- 22397581
TI  - Characterization of biologically active insulin-loaded alginate microparticles
      prepared by spray drying.
AB  - BACKGROUND: Spray drying has been used as a means to encapsulate therapeutics in
      polymeric matrices to improve stability and alter pharmacokinetics. This research
      aims to characterize alginate microparticles formed by spray drying to
      encapsulate insulin for therapeutic delivery applications. METHODS: Particle size
      was characterized by laser diffraction spectroscopy, morphology by scanning
      electron microscopy, and protein and polymer distribution by confocal laser
      scanning microscopy. In addition, particle fines collected from the spray-dryer
      exhaust unit were characterized for size and morphology. The insulin
      encapsulation efficiency (EE) was determined after particle dissolution through
      quantification by spectrophotometric analysis. An in-vitro bioassay involving
      stimulation of rat L6 myoblasts was developed to confirm the bioactivity of
      released insulin. RESULTS: Mean diameter of the product was 2.1 +/- 0.3 MUm.
      Larger particles appeared spherical, with some smaller particles presenting
      surface topography variability and divoting. Protein EE was 38.2% +/- 9.5%, with
      confocal microscopy showing the protein and polymer concentrated at the surface
      of larger particles, but more evenly distributed throughout smaller particles. A
      bioassay for the in-vitro quantification of insulin bioactivity was developed by
      calibrating the ratio of phosphorylated to total cellular protein kinase B (PKB;
      also known as AKT). in insulin-stimulated rat L6 myoblasts. Insulin released from
      the particles was 88% +/- 15% bioactive, showing that spray drying had minimal
      impact on protein structure. CONCLUSION: Spray drying was effective in producing
      microparticles containing bioactive insulin. Future studies will focus on the
      improvement of the EE and particle uniformity with the aim of developing this
      technology further for the encapsulation and delivery of peptide or protein-based
      therapeutics.

PMID- 22397582
TI  - Reaction OH + OH studied over the 298-834 K temperature and 1-100 bar pressure
      ranges.
AB  - Self-reaction of hydroxyl radicals, OH + OH -> H(2)O + O (1a) and OH + OH ->
      H(2)O(2) (1b), was studied using pulsed laser photolysis coupled to transient UV
      vis absorption spectroscopy over the 298-834 K temperature and 1-100 bar pressure
      ranges (bath gas He). A heatable high-pressure flow reactor was employed.
      Hydroxyl radicals were prepared using reaction of electronically excited oxygen
      atoms, O((1)D), produced in photolysis of N(2)O at 193 nm, with H(2)O. The
      temporal behavior of OH radicals was monitored via transient absorption of light
      from a dc discharge in H(2)O/Ar low-pressure resonance lamp at ca. 308 nm. The
      absolute intensity of the photolysis light was determined by accurate in situ
      actinometry based on the ozone formation in the presence of molecular oxygen. The
      results of this study combined with the literature data indicate that the rate
      constant of reaction 1a, associated with the pressure independent component,
      decreases with temperature within the temperature range 298-414 K and increases
      above 555 K. The pressure dependent rate constant for (1b) was parametrized using
      the Troe expression as k(1b,inf) = (2.4 +/- 0.6) * 10(-11)(T/300)(-0.5) cm(3)
      molecule(-1) s(-1), k(1b,0) = [He] (9.0 +/- 2.2) * 10(-31)(T/300)(-3.5+/-0.5)
      cm(3) molecule(-1) s(-1), F(c) = 0.37.

PMID- 22397580
TI  - Knowledge, attitudes and other factors associated with assessment of tobacco
      smoking among pregnant Aboriginal women by health care providers: a cross
      sectional survey.
AB  - BACKGROUND: As with many Indigenous peoples, smoking rates among Aboriginal
      Australians are considerably higher than those of the non-Indigenous population.
      Approximately 50% of Indigenous women smoke during pregnancy, a time when women
      are more motivated to quit. Antenatal care providers are potentially important
      change agents for reducing the harms associated with smoking, yet little is known
      about their knowledge, attitudes or skills, or the factors associated with
      providing smoking cessation advice. METHODS: This paper aimed to explore the
      knowledge and attitudes of health care providers caring for pregnant Australian
      Aboriginal women with regard to smoking risks and cessation; and to identify
      factors associated with self-reported assessment of smoking. A cross-sectional
      survey was undertaken with 127 staff providing antenatal care to Aboriginal women
      from two jurisdictions: the Northern Territory and New South Wales, Australia.
      Measures included respondents' estimate of the prevalence of smoking among
      pregnant women; optimal and actual assessment of smoking status; knowledge of
      risks associated with antenatal smoking; knowledge of smoking cessation;
      attitudes to providing cessation advice to pregnant women; and perceived barriers
      and motivators for cessation for pregnant women. RESULTS: The median provider
      estimate of the smoking prevalence was 69% (95%CI: 60,70). The majority of
      respondents considered assessment of smoking status to be integral to antenatal
      care and a professional responsibility. Most (79%) indicated that they assess
      smoking status in 100% of clients. Knowledge of risks was generally good, but
      knowledge of cessation was poor. Factors independently associated with assessing
      smoking status among all women were: employer service type (p = 0.025); cessation
      knowledge score (p = 0.011); and disagreeing with the statement that giving
      advice is not worth it given the low level of success (p = 0.011). CONCLUSIONS:
      Addressing knowledge of smoking risks and cessation counselling is a priority and
      should improve both confidence and ability, and increase the frequency and
      effectiveness of counselling. The health system must provide supports to
      providers through appropriate policy and resourcing, to enable them to address
      this issue.

PMID- 22397583
TI  - Determination of peptide-surface adsorption free energy for material surfaces not
      conducive to SPR or QCM using AFM.
AB  - The interactions between peptides and proteins with material surfaces are of
      primary importance in many areas of biotechnology. While surface plasmon
      resonance spectroscopy (SPR) and quartz crystal microbalance (QCM) methods have
      proven to be very useful in measuring fundamental properties characterizing
      adsorption behavior, such as the free energy of adsorption for peptide-surface
      interactions, these methods are largely restricted to use for materials that can
      readily form nanoscale-thick films over the respective sensor surfaces. Many
      materials including most polymers, ceramics, and inorganic glasses, however, are
      not readily suitable for use with SPR or QCM methods. To overcome these
      limitations, we recently showed that desorption forces (F(des)) obtained using a
      standardized AFM method linearly correlate to standard-state adsorption free
      energy values (DeltaG degrees (ads)) measured from SPR in phosphate buffered
      saline (PBS: phosphate buffered 140 mM NaCl, pH 7.4). This approach thus provides
      a means to determine DeltaG degrees (ads) for peptide adsorption using AFM that
      can be applied to any flat material surface. In this present study, we
      investigated the F(des)-DeltaG degrees (ads) correlation between AFM and SPR data
      in PBS for a much broader range of systems including eight different types of
      peptides on a set of eight different alkanethiol self-assembled monolayer (SAM)
      surfaces. The resulting correlation was then used to estimate DeltaG degrees
      (ads) from F(des) determined by AFM for selected bulk polymer and glass/ceramic
      materials such as poly(methyl methacrylate) (PMMA), high-density polyethylene
      (HDPE), fused silica glass, and a quartz (100) surface. The results of these
      studies support our previous findings regarding the strong correlation between
      F(des) measured by AFM and DeltaG degrees (ads) determined by SPR, and provides a
      means to estimate DeltaG degrees (ads) for peptide adsorption on macroscopically
      thick samples of materials that are not conducive for use with SPR or QCM.

PMID- 22397584
TI  - Assessment of 8-oxo-7, 8-dihydro-2'-deoxyguanosine and malondialdehyde levels as
      oxidative stress markers and antioxidant status in non-small cell lung cancer.
AB  - OBJECTIVE: The present investigation was taken up to evaluate the 8-oxo-7,8
      dihydro-2'-deoxyguanosine and malondialdehyde as markers of oxidative stress, the
      levels of antioxidants and the correlations between these oxidative stress
      markers and antioxidants in lung cancer patients. METHODS: The study included 222
      patients (158 men and 64 women, age ranging from 32 to 85 years) and 207 control
      subjects (153 men and 54 women, aged 30-80 years) for the analysis of urinary
      excretion of 8-oxodG using an ELISA assay, plasma malondialdehyde using
      spectrophotometer and red cell Cu-Zn SOD and GPx activities by kit methods.
      RESULTS: The levels of 8-oxodG and malondialdehyde were significantly higher (p <
      0.001) and red cell superoxide dismutase and glutathione peroxidase activities (p
      < 0.001) were significantly lower in lung cancer patients than in controls. There
      was a significantly positive correlation between 8-oxodG and malondialdehyde
      (r=0.912, p < 0.001) and a negative correlation between 8-oxodG and antioxidants.
      CONCLUSIONS: Our results demonstrate that an increased rate of oxidative stress
      might play a role in the pathogenesis of lung cancer as evidenced by a failure in
      the oxidant/antioxidant balance in favour of lipid peroxidation and DNA damage.

PMID- 22397585
TI  - Improvement of the lipid profile in post menopausal women who use estradiol and
      testosterone implants.
AB  - OBJECTIVE: This study evaluating the lipid profile in women in post menopause
      using the hormone therapy (HT) with implants of estradiol and testosterone.
      METHOD: One year prospective cohort with 122 patients separated in group 1, not
      using HT, group 2 starting the use of HT, and group 3 with prior use of implants
      of estradiol and testosterone. All patients performed serum dosages of total
      cholesterol, HDL and triglycerides, in the beginning of the study and after 1
      year. DISCUSSION: The use of E and T implants showed some statistically
      significant decrease in TC at the beginning of the HT and some decrease in LDL in
      the group using HT. In the group without HT there was no difference in lipid
      profile.

PMID- 22397587
TI  - Optical spectroscopic exploration of binding of Cochineal Red A with two
      homologous serum albumins.
AB  - Cochineal Red A is a negatively charged synthetic azo food colorant and a
      potential carcinogen. We present here the study of binding of Cochineal Red A
      with two homologous serum albumins, human (HSA) and bovine (BSA), in aqueous pH
      7.4 buffer by optical spectroscopic techniques. Protein intrinsic fluorescence
      quenching by Cochineal Red A occurs through ground-state static interaction and
      its binding with BSA is stronger than with HSA. The magnitudes of thermodynamic
      parameters suggest that dye binding occurs principally via electrostatic
      complexation. Site-marker competitive binding shows that Cochineal Red A binds
      primarily to site I of serum albumins. Circular dichroic spectra indicate that
      dye binding results in some conformational modification of serum albumins.
      Increased ionic strength of the medium results in lowering of binding. This study
      provides an important insight into possible means of removal of dye toxicity.

PMID- 22397586
TI  - Quantitative changes in intracellular calcium and extracellular-regulated kinase
      activation measured in parallel in CHO cells stably expressing serotonin (5-HT) 5
      HT2A or 5-HT2C receptors.
AB  - BACKGROUND: The serotonin (5-HT) 2A and 2C receptors (5-HT2AR and 5-HT2CR) are
      involved in a wide range of physiological and behavioral processes in the
      mammalian central and peripheral nervous systems. These receptors share a high
      degree of homology, have overlapping pharmacological profiles, and utilize many
      of the same and richly diverse second messenger signaling systems. We have
      developed quantitative assays for cells stably expressing these two receptors
      involving minimal cell sample manipulations that dramatically improve parallel
      assessments of two signaling responses: intracellular calcium (Cai++) changes and
      activation (phosphorylation) of downstream kinases. Such profiles are needed to
      begin to understand the simultaneous contributions from the multiplicity of
      signaling cascades likely to be initiated by serotonergic ligands. RESULTS: We
      optimized the Cai++ assay for stable cell lines expressing either 5-HT2AR or 5
      HT2CR (including dye use and measurement parameters; cell density and serum
      requirements). We adapted a quantitative 96-well plate immunoassay for pERK in
      the same cell lines. Similar cell density optima and time courses were observed
      for 5-HT2AR- and 5-HT2CR-expressing cells in generating both types of signaling.
      Both cell lines also require serum-free preincubation for maximal agonist
      responses in the pERK assay. However, 5-HT2AR-expressing cells showed significant
      release of Cai++ in response to 5-HT stimulation even when preincubated in serum
      replete medium, while the response was completely eliminated by serum in 5-HT2CR
      expressing cells. Response to another serotonergic ligand (DOI) was eliminated by
      serum-replete preincubation in both cells lines. CONCLUSIONS: These data expand
      our knowledge of differences in ligand-stimulated signaling cascades between 5
      HT2AR and 5-HT2CR. Our parallel assays can be applied to other cell and receptor
      systems for monitoring and dissecting concurrent signaling responses.

PMID- 22397588
TI  - Recent advances in the therapeutic applications of pyrazolines.
AB  - INTRODUCTION: Pyrazolines are well-known and important nitrogen-containing five
      membered ring heterocyclic compounds. Various methods have been worked out for
      their synthesis. Several pyrazoline derivatives have been found to possess
      diverse biological properties, which has stimulated research activity in this
      field. AREAS COVERED: The present review sheds light on the recent therapeutic
      patent literature (2000 - 2011) describing the applications of pyrazolines and
      their derivatives on selected activities. Many of the therapeutic applications of
      pyrazoline derivatives have been discussed, either in the patent or in the
      general literature areas in this review. In addition to selected biological data,
      a wide range of pharmaceutical applications and pharmaceutical compositions are
      also summarized. EXPERT OPINION: Pyrazoline derivatives have numerous prominent
      pharmacological effects, such as antimicrobial (antibacterial, antifungal,
      antiamoebic, antimycobacterial), anti-inflammatory, analgesic, antidepressant and
      anticancer. Further pharmacological effects include cannabinoid CB1 receptor
      antagonists, antiepileptic, antitrypanosomal, antiviral activity, MAO-inhibitory,
      antinociceptive activity, insecticidal, hypotensive, nitric oxide synthase
      inhibitor, antioxidant, steroidal and antidiabetic. Lastly, they also effect ACAT
      inhibition, urotensin II and somatostatin-5 receptors, TGF-beta signal
      transduction inhibitors and neurocytotoxicity inhibitors activities. Many new
      pyrazoline derivatives have been synthesized and patented, but there are still
      new aspects to explore and work on.

PMID- 22397589
TI  - Healthcare cost attributable to recently-diagnosed breast cancer in a privately
      insured population in the United States.
AB  - OBJECTIVE: To evaluate breast cancer-associated healthcare cost from the payer
      perspective for the initial year after diagnoses of invasive breast cancer.
      BACKGROUND: Breast cancer is the second most common malignancy in American women.
      While lifetime burden-of-care studies have reported spending between $20,000 and
      $100,000 per patient, previous studies have not outlined first year cost in
      managing this disease in recently diagnosed patients. METHODS: This study was a
      retrospective, matched cohort study of privately-insured patients. Data were from
      a large US employers' health claims database (January 2003-September 2008).
      Breast cancer cases were identified by ICD-9-CM diagnostic codes on index and
      confirmatory claims. A control group was identified with a ratio of 3:1, matched
      by demographic and health plan characteristics. Comorbidities were analyzed using
      the Charlson comorbidity index and AHRQ Comorbidity Software. A multivariate, log
      linked, generalized linear model evaluated cost contributions of breast cancer in
      relation to demographic factors, comorbidities, and plan type. RESULTS: The study
      included 35,057 cases and 105,171 matched controls (mean age 52 years). Common
      comorbidities included hypertension, diabetes, hypothyroidism, chronic pulmonary
      disease, and deficiency anemia. In the generalized linear model, the adjusted
      difference in total healthcare cost was $42,401 per patient within a year, with
      outpatient services responsible for most of this sum. Breast cancer-associated
      incremental annual costs per patient in inpatient, outpatient, and prescription
      categories were $5100, $37,231, and $1037, respectively. LIMITATIONS: These
      results may not be representative of the entire US, as data were derived from
      breast cancer patients with private, employer-based health insurance, and lacked
      covariates including race/ethnicity, education, income, and disease stage.
      CONCLUSIONS: Recently diagnosed breast cancer represents a substantial economic
      burden for US healthcare payers.

PMID- 22397590
TI  - Cost-effectiveness of dabigatran etexilate for stroke prevention in non-valvular
      atrial fibrillation. Applying RE-LY to clinical practice in Denmark.
AB  - OBJECTIVE: To estimate the economic implications of introducing dabigatran
      etexilate ('dabigatran') for anti-coagulation therapy in Danish patients with non
      valvular atrial fibrillation based on results of the RE-LY trial. METHODS: The
      lifetime cost and outcomes of dabigatran and warfarin were estimated using a
      previously published cost-effectiveness model. The model utilizes the data from
      the RE-LY study to estimate the costs and outcomes of stroke prevention in atrial
      fibrillation. Cost estimates were based on official Danish tariffs and prices,
      and published literature on the cost of stroke. In the base-case analysis a
      conservative approach was adopted applying tariffs from the lowest range for the
      cost of International Normalized Ratio (INR) monitoring associated with warfarin.
      The effectiveness measure of the analysis was quality-adjusted life-years (QALY).
      RESULTS: The model estimated that the mean cost per patient for the remaining
      life-time is euro 16,886 treated with warfarin and euro 18,752 treated with
      dabigatran. This was associated with mean QALYs per patient of 8.32 with warfarin
      and 8.59 with dabigatran. The resulting incremental cost-effectiveness ratio
      (ICER) of ~ euro 7000 per QALY gained is regarded as cost-effective by Danish
      standards. This conclusion was seen to be robust to realistic variations in input
      parameters, including adjustment for the RE-LY centres achieving the best INR
      monitoring quality. Threshold analysis revealed that dabigatran would be cost
      saving in settings where the cost of warfarin monitoring exceeds euro 744 per
      year. LIMITATIONS: The analysis does not include all aspects of Danish clinical
      practice anti-coagulation that will influence cost-effectiveness of dabigatran,
      e.g., this study did not attempt to model quality of anticoagulation monitoring
      and under-utilization in clinical practice. CONCLUSIONS: Based on the outcomes
      observed in the RE-LY trial, dabigatran represents a cost-effective alternative
      to warfarin in Denmark for all patients with atrial fibrillation within the
      licensed indication of dabigatran.

PMID- 22397591
TI  - Acute abdominal pain presenting as a rare appendiceal duplication: a case report.
AB  - INTRODUCTION: Appendiceal duplication is a rare anomaly that can manifest as
      right lower quadrant pain. There are several variations described for this
      condition. We recommend aggressive operative management should this anatomical
      variation present in the presence of acute appendicitis. CASE PRESENTATION: We
      report the case of a 15-year-old African American girl who presented to our
      hospital with right lower quadrant pain and was subsequently found to have
      appendiceal duplication. CONCLUSION: There are two categorical systems that have
      described and stratified appendiceal duplication. Both classification systems
      have been outlined and referenced in this case report. A computed tomography scan
      has been included to provide a visual aid to help identify true vermiform
      appendiceal duplication. The presence of this anatomical abnormality is not a
      reason for surgical intervention; however, should this be found in the setting of
      acute appendicitis, aggressive resection of both appendices is mandatory.

PMID- 22397592
TI  - Effect of laminarin on the expression of GRP78 and GRP94 in rat after unilateral
      ureteral obstruction.
AB  - OBJECTIVE: The objective of this study was to determine the effect of laminarin
      on the expression of kidney endoplasmic reticulum molecular chaperones (GRP78 and
      GRP94) in rats with renal interstitial fibrosis. MATERIAL AND METHODS: A renal
      interstitial fibrosis model in rats was developed by unilateral ureteral
      obstruction (UUO). Rats were randomly divided into control group, model group,
      enalapril group, laminarin high-dosage group, laminarin median-dosage group and
      laminarin low-dosage group. The rats were killed 7 days after surgery and blood
      samples were collected. Serum creatinine (SCr) and blood urea nitrogen (BUN)
      levels were determined. Renal tubular damage index was determined by hematoxylin
      and eosin staining. The percentage of areas with renal interstitial fibrosis
      collagen was determined by the Masson staining method. Expression of kidney
      tissue endoplasmic reticulum stress (ERS) protein GRP78 and molecular chaperone
      GRP94 was determined by Western blotting. RESULTS: Tubulointerstitial injury
      index, renal interstitial fibrosis, SCr level, BUN level and expressions of GRP78
      and GRP94 were significantly different between the model group and treatment
      groups (p < 0.01). Expressions of GRP78 and GRP94 in rat nephridial tissue was
      increased (p < 0. 05), tubulointerstitial injury and renal interstitial fibrosis
      degree were decreased (p < 0.05) and renal function, SCr and BUN were decreased
      (p < 0.05) compared to those in the laminarin medium-dosage group. CONCLUSIONS:
      The results demonstrate that UUO activated the reaction of ERS and increased the
      expression of GRP78 and GRP94 in the early period after laminarin was applied,
      which helped the refolding, assembling and membrane transportation of denatured
      proteins. Consequently, the ERS signal transduction pathway was blocked,
      apoptosis was prevented and the development of renal interstitial fibrosis was
      reduced.

PMID- 22397593
TI  - Measurements of secondary organic aerosol formed from OH-initiated photo
      oxidation of isoprene using online photoionization aerosol mass spectrometry.
AB  - Isoprene is a significant source of atmospheric organic aerosol; however, the
      secondary organic aerosol (SOA) formation and involved chemical reaction pathways
      have remained to be elucidated. Recent works have shown that the photo-oxidation
      of isoprene leads to form SOA. In this study, the chemical composition of SOA
      from the OH-initiated photo-oxidation of isoprene, in the absence of seed
      aerosols, was investigated through the controlled laboratory chamber experiments.
      Thermal desorption/tunable vacuum-ultraviolet photoionization time-of-flight
      aerosol mass spectrometry (TD-VUV-TOF-PIAMS) was used in conjunction with the
      environmental chamber to study SOA formation. The mass spectra obtained at
      different photon energies and the photoionization efficiency (PIE) spectra of the
      SOA products can be obtained in real time. Aided by the ionization energies (IE)
      either from the ab initio calculations or the literatures, a number of SOA
      products were proposed. In addition to methacrolein, methyl vinyl ketone, and 3
      methyl-furan, carbonyls, hydroxycarbonyls, nitrates, hydroxynitrates, and other
      oxygenated compounds in SOA formed in laboratory photo-oxiadation experiments
      were identified, some of them were investigated for the first time. Detailed
      chemical identification of SOA is crucial for understanding the photo-oxidation
      mechanisms of VOCs and the eventual formation of SOA. Possible reaction
      mechanisms will be discussed.

PMID- 22397595
TI  - Hydrogen activation and metal hydride formation trigger cluster formation from
      supported iridium complexes.
AB  - The formation of iridium clusters from supported mononuclear iridium complexes in
      H(2) at 300 K and 1 bar was investigated by spectroscopy and atomic-resolution
      scanning transmission electron microscopy. The first steps of cluster formation
      from zeolite-supported Ir(C(2)H(4))(2) complexes are triggered by the activation
      of H(2) and the formation of iridium hydride, accompanied by the breaking of
      iridium-support bonds. This reactivity can be controlled by the choice of ligands
      on the iridium, which include the support.

PMID- 22397594
TI  - Translatability scoring in drug development: eight case studies.
AB  - Translational medicine describes the transfer of basic in vitro and in vivo data
      into human applications. In the light of low rates of market approvals for new
      medical entities, better strategies to predict the risk of drug development
      should be used to increase output and reduce costs. Recently, a scoring system to
      assess the translatability of early drug projects has been proposed. Here eight
      drugs from different therapeutic areas have been subjected to a retrospective
      test-run in this system fictively located at the phase II-III transition. The
      scores gained here underline the importance of biomarker quality which is pivotal
      to decrease the risk of the project in all cases. This is particularly evident
      for gefitinib. The EGFR mutation status is a breakthrough biomarker to predict
      therapeutic success which made this compound clinically acceptable, and this is
      plausibly reflected by a considerable increase of the translatability score. For
      psychiatric and Alzheimer's drugs, and for a CETP-inhibitor, the lack of suitable
      biomarkers and animal models is reflected by a low translatability score, well
      correlating with the excessive translational risk in these areas. These case
      studies document the apparent utility of the scoring system, at least under
      retrospective conditions, as the scores correlate with the outcomes at the level
      of market approval. Prospective validation is still missing, but these case
      studies are encouraging.

PMID- 22397596
TI  - Influence of ion size and charge on osmosis.
AB  - Osmosis is fundamental to many processes, such as in the function of biological
      cells and in industrial desalination to obtain clean drinking water. The choice
      of solute in industrial applications of osmosis is highly important in maximizing
      efficiency and minimizing costs. The macroscale process of osmosis originates
      from the nanoscale properties of the solvent, and therefore an understanding of
      the mechanisms of how these properties determine osmotic strength can be highly
      useful. For this reason, we have undertaken molecular dynamics simulations to
      systematically study the influence of ion size and charge on the strength of
      osmosis of water through carbon nanotube membranes. Our results show that strong
      osmosis occurs under optimum conditions of ion placement near the region of high
      water density near the membrane wall and of maintenance of a strong water
      hydration shell around the ions. The results in turn allow greater insight into
      the origin of the strong osmotic strength of real ions such as NaCl. Finally, in
      terms of practical simulation, we highlight the importance of avoiding size
      effects that can occur if the simulation cell is too small.

PMID- 22397597
TI  - Patient, physician, encounter, and billing characteristics predict the accuracy
      of syndromic surveillance case definitions.
AB  - BACKGROUND: Syndromic surveillance systems are plagued by high false-positive
      rates. In chronic disease monitoring, investigators have identified several
      factors that predict the accuracy of case definitions based on diagnoses in
      administrative data, and some have even incorporated these predictors into novel
      case detection methods, resulting in a significant improvement in case definition
      accuracy. Based on findings from these studies, we sought to identify physician,
      patient, encounter, and billing characteristics associated with the positive
      predictive value (PPV) of case definitions for 5 syndromes (fever,
      gastrointestinal, neurological, rash, and respiratory (including influenza-like
      illness)). METHODS: The study sample comprised 4,330 syndrome-positive visits
      from the claims of 1,098 randomly-selected physicians working in Quebec, Canada
      in 2005-2007. For each visit, physician-facilitated chart review was used to
      assess whether the same syndrome was present in the medical chart (gold
      standard). We used multivariate logistic regression analyses to estimate the
      association between claim-chart agreement about the presence of a syndrome and
      physician, patient, encounter, and billing characteristics. RESULTS: The
      likelihood of the medical chart agreeing with the physician claim about the
      presence of a syndrome was higher when the treating physician had billed many
      visits for the same syndrome recently (ORper 10 visit, 1.05; 95% CI, 1.01-1.08),
      had a lower workload (ORper 10 claims, 0.93; 95% CI, 0.90-0.97), and when the
      patient was younger (ORper 5 years of age, 0.96; 95% CI, 0.94-0.97), and less
      socially deprived (ORmost versus least deprived, 0.76; 95% CI, 0.60-0.95).
      CONCLUSIONS: Many physician, patient, encounter, and billing characteristics
      associated with the PPV of surveillance case definition are accessible to public
      health, and could be used to reduce false-positive alerts by surveillance
      systems, either by focusing on the data most likely to be accurate, or by
      adjusting the observed data for known biases in diagnosis reporting and
      performing surveillance using the adjusted values.

PMID- 22397598
TI  - Electronic structure and reactivity of cobalt oxide dimers and their hexacarbonyl
      complexes: a density functional study.
AB  - The dimers of cobalt oxide (CoO)(2) with cyclic and open bent structure are
      studied with the B1LYP density functional; the ordering of states is validated by
      the CCSD(T) method. The D(2h)-symmetry rhombic dioxide Co(2)O(2) with
      antiferromagnetically ordered electrons on cobalt centers is the global minimum.
      The cyclic peroxide Co(2)(O(2)) with side-on-bonded dioxygen in (7)B(2) ground
      state is separated from the global minimum by an energy gap of 3.15 eV. The
      dioxide is highly reactive as indicated by the high value of proton affinity and
      chemical reactivity indices. The four-member ring structures are more stable than
      those with three-member ring or chain configuration. The thermodynamic stability
      toward dissociation to CoO increases upon carbonylation, whereas proton affinity
      and reactivity with release of molecular oxygen also increase. The global minimum
      of Co(2)O(2)(CO)(6) corresponds to a triplet state (3)A" with oxygen atoms
      shifted above the molecular plane of the rhombic dioxide Co(2)O(2). The SOMO-LUMO
      gap in the ground-state carbonylated dioxide is wider, compared to the same gap
      in the bare dicobalt dioxide. The peroxo-isomer Co(2)(O(2))(CO)(6) retains the
      planar Co(2)(O(2)) ring and is only stable in a high-spin state (7)A". The
      carbonylated clusters have increased reactivity in both redox and nucleophilic
      reactions, as a result of the increased electron density in the Co(2)O(2)-ring
      area.

PMID- 22397599
TI  - Tunable micropatterned substrates based on poly(dopamine) deposition via
      microcontact printing.
AB  - A simple technique was developed to fabricate tunable micropatterned substrates
      based on mussel-inspired surface modification. Polydopamine (PDA) was developed
      on polydimethylsiloxane (PDMS) stamps and was easily imprinted to several
      substrates such as glass, silicon, gold, polystyrene, and poly(ethylene glycol)
      via microcontact printing. The imprinted PDA retained its unique reactivity and
      could modulate the chemical properties of micropatterns via secondary reactions,
      which was illustrated in this study. PDA patterns imprinted onto a cytophobic and
      nonfouling substrates were used to form patterns of cells or proteins. PDA
      imprints reacted with nucleophilic amines or thiols to conjugate molecules such
      as poly(ethylene glycol) for creating nonfouling area. Gold nanoparticles were
      immobilized onto PDA-stamped area. The reductive ability of PDA transformed
      silver ions to elemental metals as an electroless process of metallization. This
      facile and economic technique provides a powerful tool for development of a
      functional patterned substrate for various applications.

PMID- 22397601
TI  - The NIH and the regenerative medicine field.

PMID- 22397600
TI  - Comparison of pharmacokinetics in beagle dogs of nimesulide bilayer tablets with
      dispersible tablets.
AB  - The purpose of this study was to compare the in vitro release and the in vivo
      pharmacokinetics of bilayer tablets with the conventional dispersible tablets of
      nimesulide. The tablets were administered to beagle dogs and the plasma levels of
      nimesulide were determined by high-performance liquid chromatography-MS/MS. The
      pharmacokinetic parameters were calculated using a noncompartmental model. The
      bilayer tablets showed a biphasic in vitro release pattern with initial burst
      release and sustained release following the quasi-Fickian diffusion-based release
      mechanism. The C(max), t(max), mean residence time (MRT), and area under the
      curve from 0 to 36 h were 10.8 +/- 4.2 MUg/mL, 2.3 +/- 1.0 h, 6.7 +/- 2.1 h, 81.5
      +/- 26.7 MUg.h/mL for the bilayer tablets and 14.8 +/- 5.8 MUg/mL, 2.7 +/- 0.8 h,
      5.6 +/- 0.9 h, 95.4 +/- 44.2 MUg.h/mL for the dispersible tablets. Compared with
      the dispersible tablets, the bilayer tablets have lower C(max), similar t(max),
      and longer MRT. The aforementioned pharmacokinetic parameters, especially the MRT
      demonstrated to be valuable for evaluating the biphasic characteristics. This
      study provides a promising in vivo evaluation method for the bilayer tablets with
      biphasic release pattern.

PMID- 22397602
TI  - Use of endometrial stem cells in regenerative medicine.

PMID- 22397605
TI  - Chromosomal characterization of cryopreserved mesenchymal stem cells from the
      human subendothelium umbilical cord vein.
AB  - AIMS: To conduct a morphological, functional and chromosomal characterization of
      mesenchymal stem cell populations from the human subendothelium umbilical cord
      vein after cryopreservation. MATERIAL & METHODS: Five human umbilical cords were
      processed in order to obtain mesenchymal stem cells. Flow cytometry,
      differentiation assays and cytogenetic analysis were carried out before and after
      the cryopreservation process. RESULTS: Flow cytometry revealed that CD105, CD73
      and CD90 markers were expressed by the cells, which lacked the expression of
      hematopoietic lineage markers, such as CD14, CD34 and CD45. The mesenchymal stem
      cells demonstrated capacity for osteogenic, adipogenic and chondrogenic
      differentiation. Chromosome analysis showed no clonal chromosome changes in the
      cells in either situation. However, a significant number of nonclonal chromosomal
      aberrations were apparent after cryopreservation, including monosomies and
      structural changes. Cells isolated from one umbilical cord exhibited a rare
      balanced paracentric inversion, likely a cytogenetic constitutional alteration.
      This was present both before and after experimental procedures. CONCLUSION: These
      findings show that using mesenchymal stem cells for clinical approaches requires
      careful investigation and sensitive tests in order to ensure cellular therapy
      biosafety.

PMID- 22397606
TI  - A comprehensive protein expression profile of extracellular matrix biomaterial
      derived from porcine urinary bladder.
AB  - AIMS: To generate a comprehensive profile of the protein composition of
      xenogeneic biomaterial, derived from porcine urinary bladder matrix (UBM).
      MATERIALS & METHODS: Tunica layers and muscularis mucosa were removed from
      bladders using mechanical delamination. UBM was prepared using a solution of
      peracetic acid in ethanol, lyophilized then milled into powder. UBM biomaterial
      was subjected to tryptic digests and components separated using high-performance
      liquid chromatography with an ion trap mass spectrometer and identified through
      databases. RESULTS: A repertoire of 129 proteins with neurotrophic,
      antiangiogenic and tumor-suppressive activities and those associated with tissue
      remodeling and wound repair were identified. CONCLUSION: This study provides the
      first insight into the complex nature of the UBM and how its application may be
      tailored for specific applications in regenerative medicine. We propose that the
      UBM be further investigated for reconstructive and regenerative remodeling of
      cardiac and dermal tissues, as well as peripheral nerves.

PMID- 22397607
TI  - Characterization of the phenotype and functionality of corneal epithelial cells
      derived from mouse embryonic stem cells.
AB  - AIMS: To investigate the optimum conditions for the differentiation of a mouse
      embryonic stem cell line towards corneal epithelial cell fate. MATERIALS &
      METHODS: The effect of conditioned media from both metabolically active (to
      produce lineage A) and growth-arrested limbal fibroblasts (lineage G) were
      compared with basal media (lineage N) in terms of morphology and marker
      expression, assessed by immunocytochemistry and reverse transcription PCR.
      Cultures were transplanted into a porcine ex vivo model to investigate their
      ability for wound healing and cornea repair. RESULTS: Lineage N exhibited
      cobblestone morphology and expressed CK12 and p63alpha, while OCT4 and SSEA1 were
      downregulated. Post-transplantation, these cells were able to multilayer and heal
      after wounding while maintaining marker expression. CONCLUSION: Lineages with
      corneal epithelial-like characteristics, which are derived from embryonic stem
      cells, have potential for use in the study of corneal wound healing and therapy.

PMID- 22397608
TI  - Attitudes of the UK ear, nose and throat clinical community to the future
      potential use of stem cell therapies to treat deafness.
AB  - AIMS: Hearing loss is commonly due to the degeneration and death of hair cells
      and their associated spiral ganglion neurons. A total of 250 million people are
      affected worldwide. Stem cell treatments offer new and powerful strategies to
      enable recovery from hearing loss. This study focuses on the translational
      process required to move stem cell therapy from the laboratory to clinical use as
      a novel treatment of deafness and an alternative to conventional therapy. In
      particular, this study aims to inform and enable the adoption process for such
      therapies, including understanding the awareness of and attitudes towards stem
      cell therapy for hearing loss among ear, nose and throat surgeons, physicians,
      audiologists and scientists, who are key stakeholders in the adoption process.
      METHODS: A structured questionnaire has been developed and applied to assess the
      knowledge and awareness of the clinical community with respect to the future
      potential use of stem cell therapies to treat deafness. RESULTS: Results showed
      >87% of the clinicians sampled have very little or no knowledge of stem cell
      therapy. A total of 11% have been asked by patients about the use of stem cell
      therapies to treat deafness, and 64% felt a new treatment is needed for deafness.
      Significantly, 40% felt that a stem cell therapy would be a good adjuvant to a
      cochlear implant. In total, 78% were supportive of investment in stem cell
      therapy research and manufacturing. This investment should be in work directed at
      those areas where clinicians favor adoption. CONCLUSION: Alignment is required
      between the scientific and clinical communities. This should not only take into
      account the likelihood of scientific success when pursuing the therapeutic
      alternatives, but should also consider the clinical trial requirements,
      regulatory landscape and reimbursement conditions for each option.

PMID- 22397610
TI  - Biomaterials combined with cell therapy for treatment of spinal cord injury.
AB  - Spinal cord injury (SCI) is a devastating traumatic injury resulting in paralysis
      or sensory deficits due to tissue damage and the poor ability of axons to
      regenerate across the lesion. Despite extensive research, there is still no
      effective treatment that would restore lost function after SCI. A possible
      therapeutic approach would be to bridge the area of injury with a bioengineered
      scaffold that would create a stimulatory environment as well as provide guidance
      cues for the re-establishment of damaged axonal connections. Advanced scaffold
      design aims at the fabrication of complex materials providing the concomitant
      delivery of cells, neurotrophic factors or other bioactive substances to achieve
      a synergistic effect for treatment. This review summarizes the current
      utilization of scaffolding materials for SCI treatment in terms of their
      physicochemical properties and emphasizes their use in combination with various
      cell types, as well as with other combinatorial approaches promoting spinal cord
      repair.

PMID- 22397612
TI  - Stem cell therapy for multiple sclerosis: preclinical evidence beyond all doubt?
AB  - Stem cell transplantation holds great promise for restoration of neural function
      in various neurodegenerative disorders, including multiple sclerosis (MS).
      However, many questions remain regarding the true efficacy and precise mode of
      action of stem cell-based therapeutic approaches. Therefore, in this article, we
      will first discuss the ideal route and/or timing of stem cell-based therapies for
      experimental autoimmune encephalomyelitis (EAE), the most used preclinical animal
      model for MS. Next, we will provide an overview of the proposed mechanisms that
      contribute to the beneficial effects of stem cell transplantation observed during
      the treatment of rodent EAE. Reviews of current and past literature clearly
      demonstrate conceptual changes in the development of stem cell-based approaches
      for EAE/MS, leading to the identification of several major challenges to be
      tackled before (stem) cell therapy for rodent EAE can be safely and successfully
      translated to human therapy for MS.

PMID- 22397611
TI  - Human adipose-derived cells: an update on the transition to clinical translation.
AB  - The pace of discovery involving adipose-derived cells continues to accelerate at
      both the preclinical and clinical translational levels. Adipose tissue is a
      source of freshly isolated, heterogeneous stromal vascular fraction cells and
      culture-expanded, adherent and relatively homogeneous adipose stromal/stem cells.
      Both populations display regenerative capacity in soft and hard tissue repair,
      ischemic insults and autoimmune diseases. While their major mechanism of action
      has been attributed to both direct lineage differentiation and/or paracrine
      factor release, current evidence favors a paracrine mechanism. Over 40 clinical
      trials using adipose-derived cells conducted in 15 countries have been registered
      with the NIH, the majority of which are Phase I or Phase I/II safety studies.
      This review focuses on the literature of the past 2 years in order to assess the
      status of clinical and preclinical studies on adipose-derived cell therapies for
      regenerative medicine.

PMID- 22397609
TI  - Functional cardiac tissue engineering.
AB  - Heart attack remains the leading cause of death in both men and women worldwide.
      Stem cell-based therapies, including the use of engineered cardiac tissues, have
      the potential to treat the massive cell loss and pathological remodeling
      resulting from heart attack. Specifically, embryonic and induced pluripotent stem
      cells are a promising source for generation of therapeutically relevant numbers
      of functional cardiomyocytes and engineering of cardiac tissues in vitro. This
      review will describe methodologies for successful differentiation of pluripotent
      stem cells towards the cardiovascular cell lineages as they pertain to the field
      of cardiac tissue engineering. The emphasis will be placed on comparing the
      functional maturation in engineered cardiac tissues and developing heart and on
      methods to quantify cardiac electrical and mechanical function at different
      spatial scales.

PMID- 22397615
TI  - Processing of musical structure by high-functioning adolescents with autism
      spectrum disorders.
AB  - Enhanced pitch perception and memory have been cited as evidence of a local
      processing bias in autism spectrum disorders (ASD). This bias is argued to
      account for enhanced perceptual functioning ( Mottron & Burack, 2001 ; Mottron,
      Dawson, Soulieres, Hubert, & Burack, 2006 ) and central coherence theories of ASD
      ( Frith, 1989 ; Happe & Frith, 2006 ). A local processing bias confers a
      different cognitive style to individuals with ASD ( Happe, 1999 ), which accounts
      in part for their good visuospatial and visuoconstructive skills. Here, we
      present analogues in the auditory domain, audiotemporal or audioconstructive
      processing, which we assess using a novel experimental task: a musical puzzle.
      This task evaluates the ability of individuals with ASD to process temporal
      sequences of musical events as well as various elements of musical structure and
      thus indexes their ability to employ a global processing style. Musical
      structures created and replicated by children and adolescents with ASD (10-19
      years old) and typically developing children and adolescents (7-17 years old)
      were found to be similar in global coherence. Presenting a musical template for
      reference increased accuracy equally for both groups, with performance associated
      to performance IQ and short-term auditory memory. The overall pattern of
      performance was similar for both groups; some puzzles were easier than others and
      this was the case for both groups. Task performance was further found to be
      correlated with the ability to perceive musical emotions, more so for typically
      developing participants. Findings are discussed in light of the empathizing
      systemizing theory of ASD ( Baron-Cohen, 2009 ) and the importance of describing
      the strengths of individuals with ASD ( Happe, 1999 ; Heaton, 2009 ).

PMID- 22397614
TI  - Ageing in general practice (AGP) trial: a cluster randomised trial to examine the
      effectiveness of peer education on GP diagnostic assessment and management of
      dementia.
AB  - BACKGROUND: Dementia is increasing in prevalence as the population ages. An
      earlier rather than later diagnosis allows persons with dementia and their
      families to plan ahead and access appropriate management. However, most diagnoses
      are made by general practitioners (GPs) later in the course of the disease and
      are associated with management that is poorly adherent to recommended guidelines.
      This trial examines the effectiveness of a peer led dementia educational
      intervention for GPs. METHODS: The study is a cluster randomised trial, conducted
      across three states and five sites. All GPs will complete an audit of their
      consenting patients aged 75 years or more at three time points - baseline, 12 and
      24 months. GPs allocated to the intervention group will receive two educational
      sessions from a peer GP or nurse, and will administer the GPCOG to consenting
      patients at baseline and 12 months. The first education session will provide
      information about dementia and the second will provide individualised feedback on
      audit results. GPs in the waitlist group will receive the RACGP Guidelines by
      post following the 12 month audit OUTCOMES: Primary outcomes are carer and
      consumer quality of life and depression. Secondary outcomes include: rates of GP
      identification of dementia compared to a more detailed gold standard assessment
      conducted in the patient's home; GP identification of differential diagnoses
      including reversible causes of cognitive impairment; and GP referral to
      specialists, Alzheimers' Australia and support services. A "case finding" and a
      "screening" group will be compared and the psychometrics of the GPCOG will be
      examined. SAMPLE SIZE: Approximately 2,000 subjects aged 75 years and over will
      be recruited through approximately 160 GPs, to yield approximately 200 subjects
      with dementia (reducing to 168 by 24 months). DISCUSSION: The trial outlined in
      this paper has been peer reviewed and supported by the Australian National Health
      and Medical Research Council. At the time of submission of this paper 2,034
      subjects have been recruited and the intervention delivered to 114 GPs. TRIAL
      REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR):
      ACTRN12607000117415.

PMID- 22397617
TI  - Partnering analytic models and dynamic secondary ion mass spectrometry
      simulations to interpret depth profiles due to kiloelectronvolt cluster
      bombardment.
AB  - The analytical steady-state statistical sputtering model (SS-SSM) is utilized to
      interpret molecular dynamics (MD) simulations of depth profiling of Ag solids
      with keV cluster beams of C(60) and Au(3) under different incident energy and
      angle conditions. Specifically, the results of the MD simulations provide the
      input to the SS-SSM and the result is a depth profile of a delta layer. It has
      been found that the rms roughness of each system correlates with the total
      displacement yield, a new quantity introduced in this study that follows
      naturally from the SS-SSM. The results indicate that the best depth profiles
      occur when the displacement yield is low and the sputtering yield is high.
      Moreover, it is determined that the expected value of the delta layer position as
      calculated from a depth profile rather than the peak position in the depth
      profile is the best indicator of the actual delta layer position.

PMID- 22397616
TI  - Preliminary evaluation of clinical outcome and safety of ketamine as an
      anesthetic for electroconvulsive therapy in schizophrenia.
AB  - OBJECTIVES: Electroconvulsive therapy (ECT) is an effective and safe option in
      the treatment of affective disorders and schizophrenia. One parameter known to
      influence ECT treatment efficacy is the choice of narcotic, and ketamine has
      emerged as an interesting alternative to conventional anaesthetics like
      barbiturates since it does not negatively influence seizure threshold. However,
      due to the potential to provoke dissociative symptoms, ketamine anaesthesia is
      rather hesitantly used in schizophrenia patients for fear of causing disease
      exacerbation. METHODS: We retrospectively investigated clinical outcome and
      safety in patients treated with ECT for schizophrenia and receiving ketamine
      anaesthesia, either exclusively or as switch from another narcotic and compared
      seizure parameters to a group of ECT-treated schizophrenia patients with
      thiopental anaesthesia. RESULTS: In none of the six patients undergoing ECT with
      ketamine did we observe disease exacerbation, and except for one patient, all
      patients responded or remitted under ECT. A preliminary analysis of seizure
      parameters shows an association with longer seizures in patients exclusively
      receiving ketamine. CONCLUSIONS: While the small sample size and retrospective
      character are limitations of our study, our preliminary results nonetheless
      challenge wide-spread preconceptions about the use of ketamine in schizophrenia
      patients and encourage further research into the option of using ketamine
      anaesthesia for ECT.

PMID- 22397618
TI  - A 1,6-ring closure mechanism for (+)-delta-cadinene synthase?
AB  - Recombinant (+)-delta-cadinene synthase (DCS) from Gossypium arboreum catalyzes
      the metal-dependent cyclization of (E,E)-farnesyl diphosphate (FDP) to the
      cadinane sesquiterpene delta-cadinene, the parent hydrocarbon of cotton
      phytoalexins such as gossypol. In contrast to some other sesquiterpene cyclases,
      DCS carries out this transformation with >98% fidelity but, as a consequence,
      leaves no mechanistic traces of its mode of action. The formation of (+)-delta
      cadinene has been shown to occur via the enzyme-bound intermediate (3R)-nerolidyl
      diphosphate (NDP), which in turn has been postulated to be converted to cis
      germacradienyl cation after a 1,10-cyclization. A subsequent 1,3-hydride shift
      would then relocate the carbocation within the transient macrocycle to expedite a
      second cyclization that yields the cadinenyl cation with the correct cis
      stereochemistry found in (+)-delta-cadinene. An elegant 1,10-mechanistic pathway
      that avoids the formation of (3R)-NDP has also been suggested. In this
      alternative scenario, the final cadinenyl cation is proposed to be formed through
      the intermediacy of trans, trans-germacradienyl cation and germacrene D. In
      addition, an alternative 1,6-ring closure mechanism via the bisabolyl cation has
      previously been envisioned. We report here a detailed investigation of the
      catalytic mechanism of DCS using a variety of mechanistic probes including, among
      others, deuterated and fluorinated FDPs. Farnesyl diphosphate analogues with
      fluorine at C2 and C10 acted as inhibitors of DCS, but intriguingly, after
      prolonged overnight incubations, they yielded 2F-germacrene(s) and a 10F
      humulene, respectively. The observed 1,10-, and to a lesser extent, 1,11
      cyclization activity of DCS with these fluorinated substrates is consistent with
      the postulated macrocyclization mechanism(s) en route to (+)-delta-cadinene. On
      the other hand, mechanistic results from incubations of DCS with 6F-FPP, (2Z,6E)
      FDP, neryl diphosphate, 6,7-dihydro-FDP, and NDP seem to be in better agreement
      with the potential involvement of the alternative biosynthetic 1,6-ring closure
      pathway. In particular, the strong inhibition of DCS by 6F-FDP, coupled to the
      exclusive bisabolyl- and terpinyl-derived product profiles observed for the DCS
      catalyzed turnover of (2Z,6E)-farnesyl and neryl diphosphates, suggested the
      intermediacy of alpha-bisabolyl cation. DCS incubations with enantiomerically
      pure [1-(2)H(1)](1R)-FDP revealed that the putative bisabolyl-derived 1,6-pathway
      proceeds through (3R)-nerolidyl diphosphate (NDP), is consistent with previous
      deuterium-labeling studies, and accounts for the cis stereochemistry
      characteristic of cadinenyl-derived sesquiterpenes. While the results reported
      here do not unambiguously rule in favor of 1,6- or 1,10-cyclization, they
      demonstrate the mechanistic versatility inherent to DCS and highlight the
      possible existence of multiple mechanistic pathways.

PMID- 22397619
TI  - Personality predispositions to depression in children of affectively-ill parents:
      the buffering role of self-esteem.
AB  - A major theory of personality predispositions to depression posits that
      individuals who possess high levels of self-criticism and/or dependency are
      vulnerable to developing depression following negative life events. The goal of
      the current study was to test this theory of personality predispositions and the
      self-esteem buffering hypothesis in a sample of youth using an idiographic
      approach, a high-risk sample, and a multiwave longitudinal design. One hundred
      forty children aged 6 to 14 completed measures of dependency, self-criticism,
      self-esteem, and depressive symptoms. Over the course of the following year, 8
      follow-up assessments were conducted 6 weeks apart during which all children were
      administered measures assessing depressive symptoms and the occurrence of
      negative events. Results of hierarchical linear modeling analyses indicated that
      higher levels of dependency were associated with greater increases in depressive
      symptoms following negative events among children possessing low, but not high,
      self-esteem. In contrast, self-criticism was not associated with changes in
      depressive symptoms over time regardless of children's levels of stress and/or
      self-esteem.

PMID- 22397620
TI  - Validity of the diagnoses atrial fibrillation and atrial flutter in a Danish
      patient registry.
AB  - OBJECTIVES: To assess the validity of the diagnoses of atrial fibrillation (AF)
      and atrial flutter (AFL) for men and women recorded in the Danish National
      Patient Registry, and to assess the relative distribution of AF and AFL. DESIGN:
      Review of medical records for incident cases of AF and/or AFL in the Diet,
      Cancer, and Health cohort study. Participants were enrolled in 1993-97 with 13.6
      years of follow-up until 30 December, 2009. RESULTS: The positive predictive
      value of the combined diagnosis of AF and/or AFL was 92.6% (95% CI 88.8%; 95.2%)
      with no significant difference between sexes (men 93.7% (133/142), women 90.8%
      (129/142)). The proportion of AFL either alone or in combination with AF was
      significantly higher in men than in women (13.5% (18/133) vs. 5.4% (7/129), p
      =0.03). The positive predictive value of the specified diagnosis of AFL was 57.5%
      for men (46/80) and 29.6% for women (8/27). CONCLUSIONS: This study shows that
      the validity of the diagnosis of AF and/or AFL is high and may be used for
      registry-based studies. A specified diagnosis of AFL was rarely used and was not
      reliable to distinguish between cases of AF and AFL.

PMID- 22397621
TI  - Effects of genotype, latitude, and weather conditions on the composition of
      sugars, sugar alcohols, fruit acids, and ascorbic acid in sea buckthorn
      (Hippophae rhamnoides ssp. mongolica) berry juice.
AB  - Sea buckthorn berries (Hippophae rhamnoides ssp. mongolica) of nine varieties
      were collected from three growth locations in five inconsecutive years (n = 152)
      to study the compositional differences of sugars, sugar alcohols, fruit acids,
      and ascorbic acid in berries of different genotypes. Fructose and glucose (major
      sugars) were highest in Chuiskaya and Vitaminaya among the varieties studied,
      respectively. Malic acid and quinic acid (major acids) were highest in Pertsik
      and Vitaminaya, respectively. Ascorbic acid was highest in Oranzhevaya and lowest
      in Vitaminaya. Berry samples of nine varieties collected from two growth
      locations in five years (n = 124) were combined to study the effects of latitude
      and weather conditions on the composition of H. rhamnoides ssp. mongolica. Sea
      buckthorn berries grown at lower latitude had higher levels of total sugar and
      sugar/acid ratio and a lower level of total acid and were supposed to have better
      sensory properties than those grown at higher latitude. Glucose, quinic acid, and
      ascorbic acid were hardly influenced by weather conditions. The other components
      showed various correlations with temperature, radiation, precipitation, and
      humidity variables. In addition, fructose, sucrose, and myo-inositol correlated
      positively with each other and showed negative correlation with malic acid on the
      basis of all the samples studied (n = 152).

PMID- 22397622
TI  - High-pressure accelerated asymmetric organocatalytic Friedel-Crafts alkylation of
      indoles with enones: application to quaternary stereogenic centers construction.
AB  - An organocatalytic Friedel-Crafts alkylation of indoles with alpha,beta
      unsaturated ketones was found to be efficiently accelerated under high-pressure
      conditions with a low loading of chiral primary amine salts with good yield and
      enantioselectivity up to 90%. This approach also allows, for the first time,
      selected indole derivatives containing quaternary stereogenic centers to be
      obtained from prochiral beta,beta-disubstituted enones with an enantioselectivity
      up to 80%.

PMID- 22397624
TI  - Does an offer for a free on-line continuing medical education (CME) activity
      increase physician survey response rate? A randomized trial.
AB  - BACKGROUND: Achieving a high response rate in a physician survey is challenging.
      Monetary incentives increase response rates but obviously add cost to a survey
      project. We wondered whether an offer of a free continuing medical education
      (CME) activity would be effective in improving survey response rate. RESULTS: As
      part of a survey of a national sample of physicians, we randomized half to an
      offer for a free on-line CME activity upon completion of a web-based survey and
      the other half to no such offer. We compared response rates between the groups. A
      total of 1214 out of 8477 potentially eligible physicians responded to our
      survey, for an overall response rate of 14.3%. The response rate among the
      control group (no offer of CME credit) was 16.6%, while among those offered the
      CME opportunity, the response rate was 12.0% (p < 0.0001). CONCLUSIONS: An offer
      for a free on-line CME activity did not improve physician survey response rate.
      On the contrary, the offer for a free CME activity actually appeared to worsen
      the response rate.

PMID- 22397623
TI  - Quantitative nanoscale analysis of IgE-FcepsilonRI clustering and coupling to
      early signaling proteins.
AB  - Antigen-mediated cross-linking of IgE bound to its receptor, FcepsilonRI,
      initiates a transmembrane signaling cascade that results in mast cell activation
      in the allergic response. Using immunogold labeling of intact RBL mast cells and
      scanning electron microscopy (SEM), we visualize molecular reorganization of IgE
      FcepsilonRI and early signaling proteins on both leaflets of the plasma membrane,
      without the need for ripped off membrane sheets. As quantified by pair
      correlation analysis, we observe dramatic changes in the nanoscale distribution
      of IgE-FcepsilonRI after binding of multivalent antigen to stimulate
      transmembrane signaling, and this is accompanied by similar clustering of Lyn and
      Syk tyrosine kinases, and adaptor protein LAT. We find that Lyn co-redistributes
      with IgE-FcepsilonRI into clusters that cross-correlate throughout 20 min of
      stimulation. Inhibition of tyrosine kinase activity reduces the numbers of both
      IgE-FcepsilonRI and Lyn in stimulated clusters. Coupling of these proteins is
      also decreased when membrane cholesterol is reduced either before or after
      antigen addition. These results provide evidence for involvement of FcepsilonRI
      phosphorylation and cholesterol-dependent membrane structure in the interactions
      that accompany IgE-mediated activation of RBL mast cells. More generally, this
      SEM view of intact cell surfaces provides new insights into the nanoscale
      organization of receptor-mediated signaling complexes in the plasma membrane.

PMID- 22397625
TI  - Enhanced catalytic activity of lipase encapsulated in PCL nanofibers.
AB  - Use of biocatalysis for industrial synthetic chemistry is on the verge of
      significant growth. Enzyme immobilization as an effective strategy for improving
      the enzyme activity has emerged from developments especially in nanoscience and
      nanotechnology. Here, lipase from Burkholderia cepacia (LBC), as an example of
      the luxuriant enzymes, was successfully encapsulated in polycaprolactone (PCL)
      nanofibers, proven by X-ray photoelectron spectroscopy (XPS) and atomic force
      microscopy (AFM). Evaluated in both organic and aqueous medium, the activation
      factor of the encapsulated enzymes in the hydrolysis reaction was generally
      higher than that in the transesterification reaction. Enhanced catalytic
      activities were found when 5-20 w/w % of LBC was loaded. The effect of different
      solvents pretreatment on the activity of immobilized LBC was also investigated.
      The highest activation factor was found up to 14 for the sample containing
      acetone-treated LBC/PCL (10 w/w %). The encapsulated lipase reserved 50% of its
      original activity after the 10th run in the transesterification reaction in
      hexane medium. The mechanism of activation of lipase catalytic ability based on
      active PCL nanofiberous matrix is proposed.

PMID- 22397626
TI  - Investigating arsenic speciation and mobilization in sediments with DGT and DET:
      a mesocosm evaluation of oxic-anoxic transitions.
AB  - Mobilization of arsenic from freshwater and estuarine sediments during the
      transition from oxic to anoxic conditions was investigated using recently
      developed diffusive sampling techniques. Arsenic speciation and Fe(II)
      concentrations were measured at high resolution (1-3 mm) with in situ diffusive
      gradients in thin films (DGT) and diffusive equilibration in thin films (DET)
      techniques. Water column anoxia induced Fe(II) and As(III) fluxes from the
      sediment. A correlation between water column Fe(II) and As(III) concentrations
      was observed in both freshwater (r(s) = 0.896, p < 0.001) and estuarine (r(s) =
      0.557, p < 0.001) mesocosms. Porewater sampling by DGT and DET techniques
      confirmed that arsenic mobilization was associated with the reductive dissolution
      of Fe(III) (hydr)oxides in the suboxic zone of the sediment; a relationship that
      was visible because of the ability to measure the coincident profiles of these
      species using combined DGT and DET samplers. The selective measurement of As(III)
      and total inorganic arsenic by separate DGT samplers indicated that As(III) was
      the primary species mobilized from the solid phase to the porewater. This
      measurement approach effectively ruled out substantial As(V) mobilization from
      the freshwater and estuarine sediments in this experiment. This study
      demonstrates the capabilities of the DGT and DET techniques for investigating
      arsenic speciation and mobilization over a range of sediment conditions.

PMID- 22397627
TI  - Prostaglandin-induced cervical remodelling in humans in the first trimester is
      associated with increased expression of specific tight junction, but not gap
      junction proteins.
AB  - BACKGROUND: Prostaglandins (PG) are widely employed to induce cervical
      remodelling (CR) in pregnancy. However, the underlying molecular mechanisms are
      not fully elucidated. Tight junctions (TJ) and gap junctions (GJ) regulate
      paracellular and intercellular solute transport respectively but their role in
      the process of CR remains unexplored. We hypothesized that the synthetic
      prostaglandin E1 analogue Misoprostol (M), widely used in clinical practice to
      induce CR, may alter TJ and GJ expression as part of the changes in the
      extracellular matrix (ECM) associated with remodelling. We investigated the
      effects of Misoprostol exposure on the expression of cervical TJ (claudins 1, 2,
      4, 5, 7 and occludin) and GJ (connexins 43, 30 and 26) in the 1st trimester.
      METHODS: Cervical biopsies were obtained from pregnant women and comparisons of
      TJ and GJ protein expression (by western blotting) and immunolocalisation (laser
      scanning confocal microscopy) made between those who were administered vaginal
      Misoprostol (n=10) and those who were not (n=5). RESULTS: We found that
      Misoprostol-treated tissue (M+) had higher expression of Claudins 1,2,4,7 and
      occludin (p<0.05) than untreated (M-) tissue. Expression levels of Claudins 1, 2
      and 4 were positively correlated to interval from Misoprostol treatment to
      biopsy, whilst occludin was negatively correlated. Misoprostol-treated cervical
      tissue demonstrated more endothelial claudin-5 and occludin, whilst expression of
      GJs were unchanged. CONCLUSION: Our observations suggest, for the first time,
      that increased expression of tight junction proteins may be one of the mechanisms
      by which Misoprostol induces CR in humans. Further studies are needed to explore
      if TJ proteins may be therapeutic targets to alter timing of CR in clinical
      practice.

PMID- 22397628
TI  - On the mechanism of alphaC polymer formation in fibrin.
AB  - Our previous studies revealed that the fibrinogen alphaC-domains undergo
      conformational changes and adopt a physiologically active conformation upon their
      self-association into alphaC polymers in fibrin. In the present study, we
      analyzed the mechanism of alphaC polymer formation and tested our hypothesis that
      self-association of the alphaC-domains occurs through the interaction between
      their N-terminal subdomains and may include beta-hairpin swapping. Our binding
      experiments performed by size-exclusion chromatography and optical trap-based
      force spectroscopy revealed that the alphaC-domains self-associate exclusively
      through their N-terminal subdomains, while their C-terminal subdomains were found
      to interact with the alphaC-connectors that tether the alphaC-domains to the bulk
      of the molecule. This interaction should reinforce the structure of alphaC
      polymers and provide the proper orientation of their reactive residues for
      efficient cross-linking by factor XIIIa. Molecular modeling of self-association
      of the N-terminal subdomains confirmed that the hypothesized beta-hairpin
      swapping does not impose any steric hindrance. To "freeze" the conformation of
      the N-terminal subdomain and prevent the hypothesized beta-hairpin swapping, we
      introduced by site-directed mutagenesis an extra disulfide bond between two beta
      hairpins of the bovine Aalpha406-483 fragment corresponding to this subdomain.
      The experiments performed by circular dichroism revealed that Aalpha406-483
      mutant containing Lys429Cys/Thr463Cys mutations preserved its beta-sheet
      structure. However, in contrast to wild-type Aalpha406-483, this mutant had lower
      tendency for oligomerization, and its structure was not stabilized upon
      oligomerization, in agreement with the above hypothesis. On the basis of the
      results obtained and our previous findings, we propose a model of fibrin alphaC
      polymer structure and molecular mechanism of assembly.

PMID- 22397630
TI  - Antisteroidogenic effects of hydrogen peroxide on rat granulosa cells.
AB  - Rat granulosa cells (GCs) were treated with human chorionic gonadotropin (hCG), 8
      bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP), forskolin, phorbol 12
      myristate 13-acetate (PMA), A23187 or pregnenolone in the absence or presence of
      hydrogen peroxide (H(2)O(2)). Different doses of trilostane were applied to GCs
      treated with steroidogenic precursors, that is, 25-hydroxy-cholesterol (25-OH-C)
      in the absence or presence of H(2)O(2). Results showed that all of the chemicals
      stimulated the progesterone (PG) release from rat GCs, but the stimulatory
      effects were inhibited by H(2)O(2) dose-dependently. 25-OH-C stimulated the PG
      release, which was inhibited by H(2)O(2) in the presence of trilostane. H(2)O(2)
      attenuated steroidogenic acute regulatory (StAR) protein expression, but did not
      alter the expression of cytochrome P450 side chain cleavage (P450scc) in Western
      blotting. This study indicated that H(2)O(2) inhibited PG production by GCs via
      cAMP pathway, protein kinase C (PKC) and the activities of intracellular calcium,
      P450scc and StAR protein.

PMID- 22397629
TI  - Nasopharyngeal flora in children with acute otitis media before and after
      implementation of 7 valent pneumococcal conjugate vaccine in France.
AB  - BACKGROUND: Several studies have investigated the impact of 7-valent pneumococcal
      conjugate vaccine (PCV7) on pneumococcal (Sp) and staphylococcal (Sa)
      nasopharyngeal (NP) carriage. Few have investigated the impact on Haemophilus
      influenzae (Hi) and Moraxella catarrhalis (Mc) carriage. We aimed to compare the
      NP carriage rates in young children with acute otitis media (AOM) before and
      after PCV7 implementation in France. METHODS: Prior to PCV7 implementation, we
      performed 4 successive randomized trials with NP samples. These studies compared
      several antibiotic regimens for treating AOM in young children (6 to 30 months).
      After PCV7 implementation, to assess the impact of the vaccination program on NP
      flora, young children with AOM were enrolled in a prospective surveillance study.
      In each study, we obtained an NP sample to analyze the carriage rates of Sp, Hi,
      Mc and Sa and the factors influencing the carriage. Standardized history and
      physical examination findings were recorded; the methods used for NP swabs
      (sampling and cultures) were the same in all studies. RESULTS: We enrolled 4,405
      children (mean age 13.9 months, median 12.8). Among the 2,598 children enrolled
      after PCV7 implementation, 98.3% were vaccinated with PCV7. In comparing the pre-
      and post-PCV7 periods, we found a slight but non-significant decrease in carriage
      rates of pneumococcus (AOR = 0.85 [0.69;1.05]), H. influenzae (AOR = 0.89
      [0.73;1.09]) and S. aureus (AOR = 0.92 [0.70;1.19]). By contrast, the carriage
      rate of M. catarrhalis increased slightly but not significantly between the 2
      periods (AOR = 1.08 [0.95;1.2]). Among Sp carriers, the proportion of PCV7
      vaccine types decreased from 66.6% to 10.7% (P < 0.001), penicillin intermediate
      resistant strains increased from 30.3% to 43.4% (P < 0.001), and penicillin
      resistant strains decreased greatly from 22.8% to 3.8% (P < 0.001). The
      proportion of Hi beta-lactamase-producing strains decreased from 38.6% to 17.1%
      (P < 0.001). CONCLUSION: The carriage rates of otopathogen species (Sp, Hi, Mc)
      and Sa did not significantly change in children with AOM after PCV7
      implementation in France. However, we observed significant changes in carriage
      rates of PCV7 vaccine serotypes and penicillin non-susceptible Sp.

PMID- 22397631
TI  - Slower growth in Medicare spending--is this the new normal?

PMID- 22397632
TI  - Directions for bipartisan Medicare reform.

PMID- 22397633
TI  - Neurotransmitter systems and neurotrophic factors in autism: association study of
      37 genes suggests involvement of DDC.
AB  - OBJECTIVES: Neurotransmitter systems and neurotrophic factors can be considered
      strong candidates for autism spectrum disorder (ASD). The serotoninergic and
      dopaminergic systems are involved in neurotransmission, brain maturation and
      cortical organization, while neurotrophic factors (NTFs) participate in
      neurodevelopment, neuronal survival and synapses formation. We aimed to test the
      contribution of these candidate pathways to autism through a case-control
      association study of genes selected both for their role in central nervous system
      functions and for pathophysiological evidences. METHODS: The study sample
      consisted of 326 unrelated autistic patients and 350 gender-matched controls from
      Spain. We genotyped 369 tagSNPs to perform a case-control association study of 37
      candidate genes. RESULTS: A significant association was obtained between the DDC
      gene and autism in the single-marker analysis (rs6592961, P = 0.00047). Haplotype
      based analysis pinpointed a four-marker combination in this gene associated with
      the disorder (rs2329340C-rs2044859T-rs6592961A-rs11761683T, P = 4.988e-05). No
      significant results were obtained for the remaining genes after applying multiple
      testing corrections. However, the rs167771 marker in DRD3, associated with ASD in
      a previous study, displayed a nominal association in our analysis (P = 0.023).
      CONCLUSIONS: Our data suggest that common allelic variants in the DDC gene may be
      involved in autism susceptibility.

PMID- 22397634
TI  - Heats of formation of MHxCly (M = Si, P, As, Sb) compounds and main group
      fluorides from high level electronic structure calculations.
AB  - Atomization energies at 0 K and heats of formation at 0 and 298 K are predicted
      for the MH(x)Cl(y) compounds (M = Si, P, As, and Sb) and for a number of
      trivalent, tetravalent, and pentavalent fluorides (SbF(3), BiF(3), GeF(4),
      SnF(4), PbF(4), AsF(5), SbF(5)) from coupled cluster theory (CCSD(T))
      calculations using correlation consistent basis sets and extrapolation to the
      complete basis set limit. Small-core, relativistic effective core potentials were
      used for the heavier elements (Ge, As, Sn, Sb, Pb, and Bi), including correlation
      of the outer core electrons. Additional scalar relativistic (for the lighter
      elements) and atomic spin-orbit corrections are included in order to achieve near
      chemical accuracy of +/-1.5 kcal/mol. Vibrational zero point energies were
      computed from scaled harmonic frequencies at the second order Moller-Plesset
      perturbation theory (MP2) level where possible. Agreement between theory and the
      available experimental data is excellent. We present a revised heat of formation
      of the antimony atom in the gas phase. The calculated values will be of use in
      predicting the behavior of chemical vapor deposition systems.

PMID- 22397635
TI  - Impact of biofouling on diffusive gradient in thin film measurements in water.
AB  - The technique of diffusive gradient in thin film (DGT) is commonly used to assess
      metal contamination in natural waters. In this paper, we assess the effect of
      biofouling on DGT measured labile concentrations in water and investigate whether
      an additional nuclepore polycarbonate membrane on the surface of DGT devices can
      limit biofilm growth. Simultaneous field deployments of DGT equipped with and
      without the additional membrane in a canal receiving wastewater were compared.
      The effect of the biofilm was also assessed in controlled laboratory experiments,
      completed by the experimental determination of several metals diffusion
      coefficients in the hydrogel and membrane systems. The biofilms effect was
      problematic only from the 10th day of accumulation. Accumulation of some elements
      is highly biased by the presence of a thick biofilm (Zn, Ni, Cd). The
      polycarbonate membrane improved the quantification of Cd and Ni but adversely
      affects the quantification of Cr and Co. A kinetic model is proposed to explain
      the biofilm role on the DGT measurement. Depending on the metals of interest, it
      is possible to limit bias due to biofilms by using an additional polycarbonate
      membrane.

PMID- 22397636
TI  - DPPH radical scavenging activity of tricin and its conjugates isolated from
      "Njavara" rice bran: a density functional theory study.
AB  - Structural, electronic, and energetic characteristics of tricin, tricin-4'-O
      (erythro-beta-guaiacylglyceryl)ether (TEGE), and tricin-4'-O-(threo-beta
      guaiacylglyceryl)ether (TTGE), isolated from "Njavara" rice bran have been
      studied using DFT to explain their experimentally determined radical scavenging
      activity (EC(50) values) in comparison with known standards such as quercetin,
      myricetin, and catechin. Among the three mechanisms proposed for explaining the
      antioxidant activity, proton coupled-electron transfer (PC-ET), sequential proton
      loss electron transfer (SPLET), and electron transfer-proton transfer (ET-PT),
      our results support the second one. The O-H bond dissociation enthalpy (BDE) and
      the spin density on the oxygen with the radical character are excellent
      descriptors of radical scavenging activity. BDE (in kcal/mol) increased in the
      order myricetin (74.6) < quercetin (78.1) < catechin (78.3) < tricin (81.5) <
      TTGE (90.6) < TEGE (91.1), while the EC(50) increased exponentially with increase
      in BDE, 20.51, 42.98, 45.07, 90.39, 208.01, and 352.04 MUg/mL for myricetin,
      quercetin, catechin, tricin, TTGE, and TEGE, respectively.

PMID- 22397637
TI  - Novel application of Eudragit RL and cholesteryl oleyl carbonate to thermo
      sensitive drug delivery system.
AB  - The Eudragit RL 100 and propylene glycol (PG) membranes with and without
      cholesteryl oleyl carbonate (COC) were prepared by the solvent casting method to
      pioneer a novel application of a thermo-sensitive drug delivery system. After
      that, the properties of these membranes were investigated by thermal, scanning,
      and porosity studies. Drug permeation studies through all membranes were carried
      out using salbuthamol sulphate (SBS) at constant temperatures (25 degrees C and
      37 degrees C), respectively. The permeability of SBS through the membranes with
      COC has been shown to be a discontinuous function of temperature, that is, their
      permeability increased steeply above the phase transition temperature (37 degrees
      C) of the COC. The thermo-sensitive permeation mechanism for the membranes might
      be based on the structure change of the membranes caused by the phase transition,
      so that the membranes could absorb more water. Considering the high biological
      safety of Eudragit RL 100 and PG membranes with and without COC might be used to
      develop a novel thermo-sensitive drug delivery system. 

PMID- 22397638
TI  - Perspectives of patients with type 1 or insulin-treated type 2 diabetes on self
      monitoring of blood glucose: a qualitative study.
AB  - BACKGROUND: Self-monitoring of blood glucose (SMBG), including self-regulation,
      is an important tool to achieve good glycemic control. However, many patients
      measure their glucose concentrations less often than is recommended. This study
      investigates patients' perspectives of SMBG and all relevant aspects influencing
      SMBG in patients with type 1 and insulin-treated type 2 diabetes. METHODS: In
      depth interviews were conducted with 13 patients with type 1 diabetes from an
      outpatient clinic and 15 patients with type 2 diabetes from general practices.
      All interviews were transcribed verbatim and analyzed using the Grounded Theory
      approach. RESULTS: A wide variety of SMBG was encountered. Perceptions, goals of
      SMBG and personal and contextual factors were identified, influencing the
      respondents' perspective of SMBG, and leading to this variety. Respondents
      experienced a discrepancy between their own and the professionals' perceptions
      and goals. Respondents' perception of SMBG ranged along a continuum from 'friend'
      to 'foe'. With respect to the goals, the respondents experienced tension between
      achieving good glycemic control and quality of life, and deliberately made their
      own choices. The performance of SMBG was tailored to their perceptions and
      personal goals. Personal and contextual factors such as hypo- or hyper
      (un)awareness, knowledge, and contact with professionals acted as either
      facilitating factors or as barriers to SMBG, depending on the respondents'
      perspective. A SMBG model was developed providing a representation of the factors
      and their interrelations.Respondents with type 1 diabetes seemed more resigned to
      their situation and SMBG was more integrated into their lives. CONCLUSIONS: From
      the patients' perspective, professionals positively present SMBG as a 'friend' in
      order to achieve strict glycemic control. Whereas patients can also perceive SMBG
      as a 'foe'. They primarily seek a personal balance between achieving glycemic
      control and quality of life, leading them to deliberately make other choices
      regarding SMBG performance than was recommended. Gaining insight and discussing
      all factors affecting SMBG will help professionals and patients come to mutually
      agreed goals and to tailor the performance of SMBG to the individual patient.
      This should result in a more optimal use of SMBG, an improved quality of life,
      and improved clinical parameters.

PMID- 22397641
TI  - Differential transform semi-numerical analysis of biofluid-particle suspension
      flow and heat transfer in non-Darcian porous media.
AB  - The differential transform method (DTM) is semi-numerical method which is used to
      study the steady, laminar buoyancy-driven convection heat transfer of a
      particulate biofluid suspension in a channel containing a porous material. A two
      phase continuum model is used. A set of variables is implemented to reduce the
      ordinary differential equations for momentum and energy conservation (for both
      phases) to a dimensionless system. DTM solutions are obtained for the
      dimensionless system under appropriate boundary conditions. We examine the
      influence of momentum inverse Stokes number (Skm), Darcy number (Da), Forchheimer
      number (Fs), particle loading parameter (pL), particle-phase wall slip parameter
      (Omega) and buoyancy parameter (B) on the fluid-phase velocity (U) and particle
      phase velocity (Up). Pade approximants are also employed to achieve satisfaction
      of boundary conditions. Excellent correlation is obtained between the DTM and
      numerical quadrature solutions. The results indicate that there is a strong
      decrease in fluid-phase velocities with increasing Darcian (first-order) drag and
      the second-order Forchheimer drag, and a weaker reduction in particle-phase
      velocity field. Fluid and particle-phase velocities are also strongly affected
      with inverse momentum Stokes number. DTM is shown to be a powerful tool providing
      engineers with an alternative simulation approach to other traditional methods
      for multi-phase computational biofluid mechanics. The model finds applications in
      haemotological separation and biotechnological processing. 

PMID- 22397639
TI  - A waitlist-controlled trial of behavioral parent training for fathers of children
      with ADHD.
AB  - Fathers, in general, have been underrepresented in studies of parent training
      outcome for children with attention deficit hyperactivity disorder (ADHD), and
      the present study aimed to investigate the efficacy of a behavioral parent
      training program developed expressly for fathers. The present investigation
      randomly assigned 55 fathers of children ages 6 to 12 with ADHD to the Coaching
      Our Acting-out Children: Heightening Essential Skills (COACHES) program or a
      waitlist control group. Outcomes for the study included objective observations of
      parent behaviors and parent ratings of child behavior. Results indicated that
      fathers in the COACHES group reduced their rates of negative talk and increased
      rates of praise as measured in parent-child observations, and father ratings of
      the intensity of problem behaviors were reduced, relative to the waitlist
      condition. Groups did not differ on observations of use of commands or father
      ratings of child behavior problems. Untreated mothers did not significantly
      improve on observational measures or behavioral ratings. This study provides
      preliminary evidence for the efficacy of the COACHES parenting program for
      fathers of children with ADHD. Results are cast in light of the larger literature
      on behavioral parent training for ADHD as well as how to best work with fathers
      of children with ADHD in treatment contexts.

PMID- 22397640
TI  - Parallel differentiation of embryonic stem cells into different cell types by a
      single gene-based differentiation system.
AB  - The generation of defined somatic cell types from pluripotent stem cells
      represents a promising system for many applications for regenerative therapy or
      developmental studies. Certain key developmental genes have been shown to be able
      to influence the fate determination of differentiating stem cells suggesting an
      alternative differentiation strategy to conventional medium-based methods. Here,
      we present a system allowing controlled, directed differentiation of embryonic
      stem cells (ESCs) solely by ectopic expression of single genes. We demonstrate
      that the myogenic master regulator myoD1 is sufficient to induce formation of
      skeletal muscle. In contrast to previous studies, our data suggest that myoD1
      induced differentiation is independent of additional differentiation-inducing or
      lineage-promoting signals and occurs even under pluripotency-promoting
      conditions. Moreover, we demonstrate that single gene-induced differentiation
      enables the controlled formation of two distinct cell types in parallel. By
      mixing ES cell lines expressing myoD1 or the neural transcription factor ngn2,
      respectively, we generated a mixed culture of myocytes and neurons. Our findings
      provide new insights in the role of key developmental genes during cell fate
      decisions. Furthermore, this study represents an interesting strategy to obtain
      mixed cultures of different cells from stem cells, suggesting a valuable tool for
      cellular development and cell-cell interaction studies.

PMID- 22397642
TI  - Hg2+-sensing system based on structures of complexes.
AB  - The first example of a new Hg(2+)-sensing system based on the structures of
      complexes is reported. The system uses a combination of a new chiral bidentate
      ligand and CD spectroscopy. Significant CD spectral changes are observed when
      Hg(2+) is added, whereas no CD spectral changes are observed in the cases of
      Li(+), Na(+), K(+), Mg(2+), Ca(2+), Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+),
      Zn(2+), Rb(+), Ag(+), Cd(2+), La(3+), Gd(3+), and Pb(2+).

PMID- 22397643
TI  - Electro-dry-adhesion.
AB  - This work presents novel conductive bioinspired dry adhesives with mushroom caps
      that enable the use of a synergistic combination of electrostatic and van der
      Waals forces (electro-dry-adhesion). An increase in shear adhesion bond strength
      of up to 2046% on a wide range of materials is measured when a maximum electrical
      field of 36.4 V MUm(-1) is applied. A suction effect, due to the shape of the dry
      adhesive fibers, on overall adhesion was not noted for electro-dry-adhesives when
      testing was performed at both atmospheric and reduced pressure. Utilization of
      electrostatics to apply a preloading force to dry adhesive fiber arrays allows
      increased adhesion even after electrostatic force generation has been halted by
      ensuring the close contact necessary for van der Waals forces to be effective. A
      comparison is made between self-preloading of the electro-dry-adhesives and the
      direct application of a normal preloading pressure resulting in nearly the same
      shear bond strength with an applied voltage of 3.33 kV on the same sample.

PMID- 22397644
TI  - Photomagnetic K(0.25)Ni(1-x)Co(x)[Fe(CN)6].nH2O and
      K(0.25)Co[Fe(CN)6](0.75y)[Cr(CN)6](0.75(1-y)).nH2O Prussian blue analogue solid
      solutions.
AB  - Magnetically bistable solid solutions of Prussian blue analogues with chemical
      formulas of K(alpha)Ni(1-x)Co(x)[Fe(CN)(6)](beta).nH(2)O (Ni(1-x)Co(x)Fe) and
      K(alpha)Co(gamma)[Fe(CN)(6)](y)[Cr(CN)(6)](1-y).nH(2)O (CoFe(y)Cr(1-y)) have been
      synthesized and studied using mass spectrometry, Mossbauer spectroscopy, X-ray
      diffraction, temperature-dependent infrared spectroscopy, and dc magnetometry.
      These compounds provide insight into interfaces between the photomagnetic Co-Fe
      Prussian blue analogue and the high-T(C) Ni-Cr Prussian blue analogue that exist
      in high-T(C) photomagnetic heterostructures. This investigation shows that the
      bistability of Co-Fe is strongly modified by metal substitution, with Ni(1
      x)Co(x)Fe stabilizing high-spin cobalt-iron pairs and CoFe(y)Cr(1-y) stabilizing
      low-spin cobalt-iron pairs, while both types of substitution cause a dramatic
      decrease in the bistability of the material.

PMID- 22397650
TI  - Intratumor heterogeneity and branched evolution revealed by multiregion
      sequencing.
AB  - BACKGROUND: Intratumor heterogeneity may foster tumor evolution and adaptation
      and hinder personalized-medicine strategies that depend on results from single
      tumor-biopsy samples. METHODS: To examine intratumor heterogeneity, we performed
      exome sequencing, chromosome aberration analysis, and ploidy profiling on
      multiple spatially separated samples obtained from primary renal carcinomas and
      associated metastatic sites. We characterized the consequences of intratumor
      heterogeneity using immunohistochemical analysis, mutation functional analysis,
      and profiling of messenger RNA expression. RESULTS: Phylogenetic reconstruction
      revealed branched evolutionary tumor growth, with 63 to 69% of all somatic
      mutations not detectable across every tumor region. Intratumor heterogeneity was
      observed for a mutation within an autoinhibitory domain of the mammalian target
      of rapamycin (mTOR) kinase, correlating with S6 and 4EBP phosphorylation in vivo
      and constitutive activation of mTOR kinase activity in vitro. Mutational
      intratumor heterogeneity was seen for multiple tumor-suppressor genes converging
      on loss of function; SETD2, PTEN, and KDM5C underwent multiple distinct and
      spatially separated inactivating mutations within a single tumor, suggesting
      convergent phenotypic evolution. Gene-expression signatures of good and poor
      prognosis were detected in different regions of the same tumor. Allelic
      composition and ploidy profiling analysis revealed extensive intratumor
      heterogeneity, with 26 of 30 tumor samples from four tumors harboring divergent
      allelic-imbalance profiles and with ploidy heterogeneity in two of four tumors.
      CONCLUSIONS: Intratumor heterogeneity can lead to underestimation of the tumor
      genomics landscape portrayed from single tumor-biopsy samples and may present
      major challenges to personalized-medicine and biomarker development. Intratumor
      heterogeneity, associated with heterogeneous protein function, may foster tumor
      adaptation and therapeutic failure through Darwinian selection. (Funded by the
      Medical Research Council and others.).

PMID- 22397651
TI  - Donepezil and memantine for moderate-to-severe Alzheimer's disease.
AB  - BACKGROUND: Clinical trials have shown the benefits of cholinesterase inhibitors
      for the treatment of mild-to-moderate Alzheimer's disease. It is not known
      whether treatment benefits continue after the progression to moderate-to-severe
      disease. METHODS: We assigned 295 community-dwelling patients who had been
      treated with donepezil for at least 3 months and who had moderate or severe
      Alzheimer's disease (a score of 5 to 13 on the Standardized Mini-Mental State
      Examination [SMMSE, on which scores range from 0 to 30, with higher scores
      indicating better cognitive function]) to continue donepezil, discontinue
      donepezil, discontinue donepezil and start memantine, or continue donepezil and
      start memantine. Patients received the study treatment for 52 weeks. The
      coprimary outcomes were scores on the SMMSE and on the Bristol Activities of
      Daily Living Scale (BADLS, on which scores range from 0 to 60, with higher scores
      indicating greater impairment). The minimum clinically important differences were
      1.4 points on the SMMSE and 3.5 points on the BADLS. RESULTS: Patients assigned
      to continue donepezil, as compared with those assigned to discontinue donepezil,
      had a score on the SMMSE that was higher by an average of 1.9 points (95%
      confidence interval [CI], 1.3 to 2.5) and a score on the BADLS that was lower
      (indicating less impairment) by 3.0 points (95% CI, 1.8 to 4.3) (P<0.001 for both
      comparisons). Patients assigned to receive memantine, as compared with those
      assigned to receive memantine placebo, had a score on the SMMSE that was an
      average of 1.2 points higher (95% CI, 0.6 to 1.8; P<0.001) and a score on the
      BADLS that was 1.5 points lower (95% CI, 0.3 to 2.8; P=0.02). The efficacy of
      donepezil and of memantine did not differ significantly in the presence or
      absence of the other. There were no significant benefits of the combination of
      donepezil and memantine over donepezil alone. CONCLUSIONS: In patients with
      moderate or severe Alzheimer's disease, continued treatment with donepezil was
      associated with cognitive benefits that exceeded the minimum clinically important
      difference and with significant functional benefits over the course of 12 months.
      (Funded by the U.K. Medical Research Council and the U.K. Alzheimer's Society;
      Current Controlled Trials number, ISRCTN49545035.).

PMID- 22397652
TI  - Enzyme-replacement therapy in life-threatening hypophosphatasia.
AB  - BACKGROUND: Hypophosphatasia results from mutations in the gene for the tissue
      nonspecific isozyme of alkaline phosphatase (TNSALP). Inorganic pyrophosphate
      accumulates extracellularly, leading to rickets or osteomalacia. Severely
      affected babies often die from respiratory insufficiency due to progressive chest
      deformity or have persistent bone disease. There is no approved medical therapy.
      ENB-0040 is a bone-targeted, recombinant human TNSALP that prevents the
      manifestations of hypophosphatasia in Tnsalp knockout mice. METHODS: We enrolled
      infants and young children with life-threatening or debilitating perinatal or
      infantile hypophosphatasia in a multinational, open-label study of treatment with
      ENB-0040. The primary objective was the healing of rickets, as assessed by means
      of radiographic scales. Motor and cognitive development, respiratory function,
      and safety were evaluated, as well as the pharmacokinetics and pharmacodynamics
      of ENB-0040. RESULTS: Of the 11 patients recruited, 10 completed 6 months of
      therapy; 9 completed 1 year. Healing of rickets at 6 months in 9 patients was
      accompanied by improvement in developmental milestones and pulmonary function.
      Elevated plasma levels of the TNSALP substrates inorganic pyrophosphate and
      pyridoxal 5'-phosphate diminished. Increases in serum parathyroid hormone
      accompanied skeletal healing, often necessitating dietary calcium
      supplementation. There was no evidence of hypocalcemia, ectopic calcification, or
      definite drug-related serious adverse events. Low titers of anti-ENB-0040
      antibodies developed in four patients, with no evident clinical, biochemical, or
      autoimmune abnormalities at 48 weeks of treatment. CONCLUSIONS: ENB-0040, an
      enzyme-replacement therapy, was associated with improved findings on skeletal
      radiographs and improved pulmonary and physical function in infants and young
      children with life-threatening hypophosphatasia. (Funded by Enobia Pharma and
      Shriners Hospitals for Children; ClinicalTrials.gov number, NCT00744042.).

PMID- 22397653
TI  - A 12-month phase 3 study of pasireotide in Cushing's disease.
AB  - BACKGROUND: Cushing's disease is associated with high morbidity and mortality.
      Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor
      binding profile, with high binding affinity for somatostatin-receptor subtype 5.
      METHODS: In this double-blind, phase 3 study, we randomly assigned 162 adults
      with Cushing's disease and a urinary free cortisol level of at least 1.5 times
      the upper limit of the normal range to receive subcutaneous pasireotide at a dose
      of 600 MUg (82 patients) or 900 MUg (80 patients) twice daily. Patients with
      urinary free cortisol not exceeding 2 times the upper limit of the normal range
      and not exceeding the baseline level at month 3 continued to receive their
      randomly assigned dose; all others received an additional 300 MUg twice daily.
      The primary end point was a urinary free cortisol level at or below the upper
      limit of the normal range at month 6 without an increased dose. Open-label
      treatment continued through month 12. RESULTS: Twelve of the 82 patients in the
      600-MUg group and 21 of the 80 patients in the 900-MUg group met the primary end
      point. The median urinary free cortisol level decreased by approximately 50% by
      month 2 and remained stable in both groups. A normal urinary free cortisol level
      was achieved more frequently in patients with baseline levels not exceeding 5
      times the upper limit of the normal range than in patients with higher baseline
      levels. Serum and salivary cortisol and plasma corticotropin levels decreased,
      and clinical signs and symptoms of Cushing's disease diminished. Pasireotide was
      associated with hyperglycemia-related adverse events in 118 of 162 patients;
      other adverse events were similar to those associated with other somatostatin
      analogues. Despite declines in cortisol levels, blood glucose and glycated
      hemoglobin levels increased soon after treatment initiation and then stabilized;
      treatment with a glucose-lowering medication was initiated in 74 of 162 patients.
      CONCLUSIONS: The significant decrease in cortisol levels in patients with
      Cushing's disease who received pasireotide supports its potential use as a
      targeted treatment for corticotropin-secreting pituitary adenomas. (Funded by
      Novartis Pharma; ClinicalTrials.gov number, NCT00434148.).

PMID- 22397655
TI  - Dysfunction of the diaphragm.

PMID- 22397656
TI  - Images in clinical medicine. Ectopic thyroid gland.

PMID- 22397654
TI  - Immunologic correlates of the abscopal effect in a patient with melanoma.
AB  - The abscopal effect is a phenomenon in which local radiotherapy is associated
      with the regression of metastatic cancer at a distance from the irradiated site.
      The abscopal effect may be mediated by activation of the immune system.
      Ipilimumab is a monoclonal antibody that inhibits an immunologic checkpoint on T
      cells, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). We report a case of
      the abscopal effect in a patient with melanoma treated with ipilimumab and
      radiotherapy. Temporal associations were noted: tumor shrinkage with antibody
      responses to the cancer-testis antigen NY-ESO-1, changes in peripheral-blood
      immune cells, and increases in antibody responses to other antigens after
      radiotherapy. (Funded by the National Institutes of Health and others.).

PMID- 22397657
TI  - Case records of the Massachusetts General Hospital. Case 7-2012. A 79-year-old
      man with pain and weakness in the legs.

PMID- 22397658
TI  - Tumor heterogeneity and personalized medicine.

PMID- 22397659
TI  - Discontinuing donepezil or starting memantine for Alzheimer's disease.

PMID- 22397660
TI  - The histone code and treatments for acute myeloid leukemia.

PMID- 22397662
TI  - Regulatory T cells in graft-versus-host disease.

PMID- 22397663
TI  - Regulatory T cells in graft-versus-host disease.

PMID- 22397665
TI  - CPAP for obstructive sleep apnea and the metabolic syndrome.

PMID- 22397666
TI  - CPAP for obstructive sleep apnea and the metabolic syndrome.

PMID- 22397667
TI  - CPAP for obstructive sleep apnea and the metabolic syndrome.

PMID- 22397669
TI  - TFAP2E-DKK4 and chemoresistance in colorectal cancer.

PMID- 22397670
TI  - Germline JAK2 mutation in a family with hereditary thrombocytosis.

PMID- 22397674
TI  - Images in clinical medicine. Lingual thyroid.

PMID- 22397675
TI  - Injectable PLA-based in situ forming implants for controlled release of
      Ivermectin a BCS Class II drug: solvent selection based on physico-chemical
      characterization.
AB  - In situ forming implants (ISI) prepared from biodegradable polymers such as
      poly(D,L-lactide) (PLA) and biocompatible solvents can be used to obtain
      sustained drug release after parenteral administration. The aim of this work was
      to study the effect of several biocompatible solvents with different physico
      chemical properties on the release of ivermectin (IVM), an antiparasitic BCS II
      drug, from in situ forming PLA-based implants. The solvents evaluated were N
      methyl-2-pyrrolidone (NMP), 2-pyrrolidone (2P), triacetine (TA) and benzyl
      benzoate (BB). Hansen's solubility parameters of solvents were used to explain
      polymer/solvent interactions leading to different rheological behaviours. The
      stability of the polymer and drug in the solvents were also evaluated by size
      exclusion and high performance liquid chromatography, respectively. The two major
      factors determining the rate of IVM release from ISI were miscibility of the
      solvent with water and the viscosity of the polymer solutions. In general, the
      release rate increased with increasing water miscibility of the solvent and
      decreasing viscosity in the following order NMP>2P>TA>BB. Scanning electron
      microscopy revealed a relationship between the rate of IVM release and the
      surface porosity of the implants, release being higher as implant porosity
      increased. Finally, drug and polymer stability in the solvents followed the same
      trends, increasing when polymer-solvent affinities and water content in solvents
      decreased. IVM degradation was accelerated by the acid environment generated by
      the degradation of the polymer but the drug did not affect PLA stability.

PMID- 22397676
TI  - Domain-swapped dimeric structure of a stable and functional de novo four-helix
      bundle protein, WA20.
AB  - To probe the potential for activity in unevolved amino acid sequence space, we
      created a third generation combinatorial library of de novo four-helix bundle
      proteins. The "artificial superfamily" of helical bundles was designed using
      binary patterning of polar and nonpolar residues, and expressed in Escherichia
      coli from a library of synthetic genes. WA20, picked from the library, is one of
      the most stable proteins in the superfamily, and has rudimentary activities such
      as esterase and lipase. Here we report the crystal structure of WA20, determined
      by the multiwavelength anomalous dispersion method. Unexpectedly, the WA20
      crystal structure is not a monomeric four-helix bundle, but a dimeric four-helix
      bundle. Each monomer comprises two long alpha-helices that intertwist with the
      helices of the other monomer. The two monomers together form a 3D domain-swapped
      four-helix bundle dimer. In addition, there are two hydrophobic pockets, which
      may potentially provide substrate binding sites. Small-angle X-ray scattering
      shows that the molecular weight of WA20 is ~25 kDa and the shape is rod-like (the
      maximum length, D(max) = ~8 nm), indicating that WA20 forms a dimeric four-helix
      bundle in solution. These results demonstrate that our de novo protein library
      contains not only simple monomeric proteins, but also stable and functional
      multimeric proteins.

PMID- 22397677
TI  - Multiscale QM/MM molecular dynamics study on the first steps of guanine damage by
      free hydroxyl radicals in solution.
AB  - Understanding the damage of DNA bases from hydrogen abstraction by free OH
      radicals is of particular importance to understanding the indirect effect of
      ionizing radiation. Previous studies address the problem with truncated DNA bases
      as ab initio quantum simulations required to study such electronic-spin-dependent
      processes are computationally expensive. Here, for the first time, we employ a
      multiscale and hybrid quantum mechanical-molecular mechanical simulation to study
      the interaction of OH radicals with a guanine-deoxyribose-phosphate DNA molecular
      unit in the presence of water, where all of the water molecules and the
      deoxyribose-phosphate fragment are treated with the simplistic classical
      molecular mechanical scheme. Our result illustrates that the presence of water
      strongly alters the hydrogen-abstraction reaction as the hydrogen bonding of OH
      radicals with water restricts the relative orientation of the OH radicals with
      respect to the DNA base (here, guanine). This results in an angular anisotropy in
      the chemical pathway and a lower efficiency in the hydrogen-abstraction
      mechanisms than previously anticipated for identical systems in vacuum. The
      method can easily be extended to single- and double-stranded DNA without any
      appreciable computational cost as these molecular units can be treated in the
      classical subsystem, as has been demonstrated here.

PMID- 22397678
TI  - A highly conserved interaction involving the middle residue of the SXN active
      site motif is crucial for function of class B penicillin-binding proteins:
      mutational and computational analysis of PBP 2 from N. gonorrhoeae.
AB  - Insertion of an aspartate residue at position 345a in penicillin-binding protein
      2 (PBP 2), which lowers the rate of penicillin acylation by ~6-fold, is commonly
      observed in penicillin-resistant strains of Neisseria gonorrhoeae. Here, we show
      that insertions of other amino acids also lower the penicillin acylation rate of
      PBP 2, but none supported growth of N. gonorrhoeae, indicating loss of essential
      transpeptidase activity. The Asp345a mutation likely acts by altering the
      interaction between its adjacent residue, Asp346, in the beta2a-beta2d hairpin
      loop and Ser363, the middle residue of the SXN active site motif. Because the
      adjacent aspartate creates ambiguity in the position of the insertion, we also
      examined if insertions at position 346a could confer decreased susceptibility to
      penicillin. However, only aspartate insertions were identified, indicating that
      only an Asp-Asp couple can confer resistance and retain transpeptidase function.
      The importance of the Asp346-Ser363 interaction was assessed by mutation of each
      residue to Ala. Although both mutants lowered the acylation rate of penicillin G
      by 5-fold, neither could support growth of N. gonorrhoeae, again indicating loss
      of transpeptidase function. Interaction between a residue in the equivalent of
      the beta2a-beta2d hairpin loop and the middle residue of the SXN motif is
      observed in crystal structures of other Class B PBPs, and its importance is also
      supported by multisequence alignments. Overall, these results suggest that this
      conserved interaction can be manipulated (e.g., by insertion) to lower the
      acylation rate by beta-lactam antibiotics and increase resistance, but only if
      essential transpeptidase activity is preserved.

PMID- 22397679
TI  - Silver-coated engineered magnetic nanoparticles are promising for the success in
      the fight against antibacterial resistance threat.
AB  - The combination of patients with poor immune system, prolonged exposure to anti
      infective drugs, and cross-infection has given rise to nosocomial infections with
      highly resistant pathogens, which is going to be a growing threat so termed
      "antibiotic resistance". Due to their significant antimicrobial activity, silver
      nanoparticles are recognized as a promising candidate to fight against resistant
      pathogens; however, there are two major shortcomings with these nanoparticles.
      First, the silver nanoparticles are highly toxic to the healthy cells; second,
      due to the protection offered by the biofilm mode of growth, the silver
      nanoparticles cannot eradicate bacterial biofilms. In order to overcome these
      limitations, this study introduces a new class of engineered multimodal
      nanoparticles comprising a magnetic core and a silver ring with a ligand gap. The
      results indicated promising capability of the designed multimodal nanoparticles
      for high-yield antibacterial effects and eradication of bacterial biofilms, while
      the particles were completely compatible with the cells. Utilizing a gold ring as
      an intermediate coating on the produced nanoparticles may exploit new
      opportunities for theranosis applications. This will require special
      consideration in future works.

PMID- 22397680
TI  - The transcription factor, Lmx1b, promotes a neuronal glutamate phenotype and
      suppresses a GABA one in the embryonic trigeminal brainstem complex.
AB  - Achieving an appropriate balance between inhibitory and excitatory neuronal fate
      is critical for development of effective synaptic transmission. However, the
      molecular mechanisms dictating such phenotypic outcomes are not well understood,
      especially in the whisker-to-barrel cortex neuraxis, an oft-used model system for
      revealing developmental mechanisms. In trigeminal nucleus principalis (PrV), the
      brainstem link in the whisker-barrel pathway, the transcription factor Lmx1b
      marks glutamatergic cells. In PrV of Lmx1b knockout mice (-/-), initial
      specification of glutamatergic vs. GABAergic cell fate is normal until embryonic
      day 14.5. Subsequently, until the day of birth, glutamatergic markers (e.g.,
      VGLUT2) stain significantly fewer PrV neurons, whereas, GABAergic markers (Pax2
      and Gad1) stain significantly more PrV cells, notably in Lmx1b null PrV cells.
      These changes also occurred in Lmx1b/Bax double-/- mice, where PrV cells are
      rescued from Lmx1b-/- induced apoptosis; thus, effects upon excitatory/inhibitory
      cell ratios do not reflect a cell death confound. Electroporation-induced ectopic
      expression of Lmx1b in an array of sites decreases numbers of neurons that
      express GABAergic markers, but increases VGLUT2+ cell numbers or stain intensity.
      Thus, Lmx1b is not involved in the initial specification of glutamatergic cell
      fate, but is essential for maintaining a glutamatergic phenotype. Other
      experiments suggest that Lmx1b acts to suppress Pax2, a promoter of GABAergic
      cell fate, in a cell-autonomous manner, which may be a mechanism for maintaining
      a functional balance of glutamatergic and GABAergic cell types in development.

PMID- 22397682
TI  - Cross-ethnic measurement equivalence of the SCARED in an outpatient sample of
      African American and non-Hispanic White youths and parents.
AB  - The present study evaluated the measurement equivalence of the Screen for Child
      Anxiety Related Emotional Disorders (SCARED) in a clinical sample of non-Hispanic
      White (NHW) and African American (AA) youths and parents. In addition, we
      explored the concurrent criterion validity of parent report on the SCARED to a
      parent diagnostic interview. Cross-ethnic measurement equivalence was examined in
      both youth self-report (ages 11-18; N = 374) and parent report (youth ages 5-18;
      N = 808) using multiple group analysis. Sensitivity, specificity, positive
      predictive value, and negative predictive value of the SCARED parent report were
      also examined. The original five-factor structure of the SCARED was replicated
      using confirmatory factor analysis for both groups using parent and youth report,
      although factor loadings were not equivalent across groups. Sensitivity and
      specificity of the SCARED-P clinical cutoff score (Total >=25) to anxiety
      diagnoses were acceptable in both ethnic groups. Although evidence for the cross
      ethnic equivalence of SCARED was limited, results suggest a similar structure of
      anxiety symptoms across NHW and AA youths while demonstrating sensitivity in
      symptom-level differences in anxiety expression. Overall, results provide
      preliminary evidence for the SCARED as an acceptable screening tool for anxiety
      symptoms in NHW and AA youths.

PMID- 22397681
TI  - Gene expression profiling of HCV genotype 3a initial liver fibrosis and cirrhosis
      patients using microarray.
AB  - BACKGROUND: Hepatitis C virus (HCV) causes liver fibrosis that may lead to liver
      cirrhosis or hepatocellular carcinoma (HCC), and may partially depend on
      infecting viral genotype. HCV genotype 3a is being more common in Asian
      population, especially Pakistan; the detail mechanism of infection still needs to
      be explored. In this study, we investigated and compared the gene expression
      profile between initial fibrosis stage and cirrhotic 3a genotype patients.
      METHODS: Gene expression profiling of human liver tissues was performed
      containing more than 22000 known genes. Using Oparray protocol, preparation and
      hybridization of slides was carried out and followed by scanning with GeneTAC
      integrator 4.0 software. Normalization of the data was obtained using MIDAS
      software and Significant Microarray Analysis (SAM) was performed to obtain
      differentially expressed candidate genes. RESULTS: Out of 22000 genes studied,
      219 differentially regulated genes found with P <= 0.05 between both groups; 107
      among those were up-regulated and 112 were down-regulated. These genes were
      classified into 31 categories according to their biological functions. The main
      categories included: apoptosis, immune response, cell signaling, kinase activity,
      lipid metabolism, protein metabolism, protein modulation, metabolism, vision,
      cell structure, cytoskeleton, nervous system, protein metabolism, protein
      modulation, signal transduction, transcriptional regulation and transport
      activity. CONCLUSION: This is the first study on gene expression profiling in
      patients associated with genotype 3a using microarray analysis. These findings
      represent a broad portrait of genomic changes in early HCV associated fibrosis
      and cirrhosis. We hope that identified genes in this study will help in future to
      act as prognostic and diagnostic markers to differentiate fibrotic patients from
      cirrhotic ones.

PMID- 22397684
TI  - Three-dimensional numerical simulation of stress induced by different lengths of
      osseointegrated implants in the anterior maxilla.
AB  - Lower survival rates were observed for the implant placed in the anterior
      maxilla. The purpose of this study was to investigate the influence of different
      implant lengths on the stress distribution around osseointegrated implants under
      a static loading condition in the anterior maxilla using a three-dimensional
      finite element analysis. The diameter of 4.0 mm external type implants of
      different lengths (8.5 mm, 10.0 mm, 11.5 mm, 13.0 mm, 15.0 mm) was used in this
      study. The anterior maxilla was assumed to be D3 bone quality. All the material
      was assumed to be homogenous, isotropic and linearly elastic. The implant-bone
      interface was constructed using a rigid element for simulating the
      osseointegrated condition. Then, 176 N of static force was applied on the middle
      of the palatoincisal line angle of the abutment at a 120 degrees angle to the
      long axis of abutment. The von Mises stress value was measured with an interval
      of 0.25 mm along the bone-implant interface. Incremental increase in implant
      length causes a gradual reduction of maximum and average von Mises stress at the
      labial portion within the implant. In the bone, higher stress was concentrated
      within cortical bone area and more distributed at the labial cortex, while
      cancellous bone showed relatively low stress concentration and even distribution.
      An increase in implant length reduced stress gradients at the cortical peri
      implant region. Implant length affects the mechanisms of load transmission to the
      osseointegrated implant. On the basis of this study the biomechanical stress
      based performance of implants placed in the anterior maxilla improves when using
      longer implants.

PMID- 22397683
TI  - Copper-mediated difluoromethylation of aryl and vinyl iodides.
AB  - Selectively fluorinated molecules are important as materials, pharmaceuticals,
      and agrochemicals, but their synthesis by simple, mild, laboratory methods is
      challenging. We report a straightforward method for the cross-coupling of aryl
      and vinyl iodides with a difluoromethyl group generated from readily available
      reagents to form difluoromethylarenes  and difluoromethyl-substituted alkenes.
      The reaction of electron-neutral, electron-rich, and sterically hindered aryl and
      vinyl iodides with the combination of CuI, CsF and TMSCF(2)H leads to the
      formation of difluoromethyl-substituted products in high yield with good
      functional group compatibility. This transformation is surprising, in part,
      because of the prior observation of the instability of CuCF(2)H.

PMID- 22397686
TI  - SpiroESTdb: a transcriptome database and online tool for sparganum expressed
      sequences tags.
AB  - BACKGROUND: Sparganum (plerocercoid of Spirometra erinacei) is a parasite that
      possesses the remarkable ability to survive by successfully modifying its
      physiology and morphology to suit various hosts and can be found in various
      tissues, even the nervous system. However, surprisingly little is known about the
      molecular function of genes that are expressed during the course of the parasite
      life cycle. To begin to decipher the molecular processes underlying gene
      function, we constructed a database of expressed sequence tags (ESTs) generated
      from sparganum. FINDINGS: SpiroESTdb is a web-based information resource that is
      built upon the annotation and curation of 5,655 ESTs data. SpiroESTdb provides an
      integrated platform for expressed sequence data, expression dynamics, functional
      genes, genetic markers including single nucleotide polymorphisms and tandem
      repeats, gene ontology and KEGG pathway information. Moreover, SpiroESTdb
      supports easy access to gene pages, such as (i) curation and query forms, (ii) in
      silico expression profiling and (iii) BLAST search tools. Comprehensive
      descriptions of the sparganum content of all sequenced data are available,
      including summary reports. The contents of SpiroESTdb can be viewed and
      downloaded from the web (http://pathod.cdc.go.kr/spiroestdb). CONCLUSIONS: This
      integrative web-based database of sequence data, functional annotations and
      expression profiling data will serve as a useful tool to help understand and
      expand the characterization of parasitic infections. It can also be used to
      identify potential industrial drug targets and vaccine candidate genes.

PMID- 22397685
TI  - Postnatal liver growth and regeneration are independent of c-myc in a mouse model
      of conditional hepatic c-myc deletion.
AB  - BACKGROUND: The transcription factor c-myc regulates genes involved in hepatocyte
      growth, proliferation, metabolism, and differentiation. It has also been assigned
      roles in liver development and regeneration. In previous studies, we made the
      unexpected observation that c-Myc protein levels were similar in proliferating
      fetal liver and quiescent adult liver with c-Myc displaying nucleolar
      localization in the latter. In order to investigate the functional role of c-Myc
      in adult liver, we have developed a hepatocyte-specific c-myc knockout mouse, c
      mycfl/fl;Alb-Cre. RESULTS: Liver weight to body weight ratios were similar in
      control and c-myc deficient mice. Liver architecture was unaffected. Conditional
      c-myc deletion did not result in compensatory induction of other myc family
      members or in c-Myc's binding partner Max. Floxed c-myc did have a negative
      effect on Alb-Cre expression at 4 weeks of age. To explore this relationship
      further, we used the Rosa26 reporter line to assay Cre activity in the c-myc
      floxed mice. No significant difference in Alb-Cre activity was found between
      control and c-mycfl/fl mice. c-myc deficient mice were studied in a
      nonproliferative model of liver growth, fasting for 48 hr followed by a 24 hr
      refeeding period. Fasting resulted in a decrease in liver mass and liver protein,
      both of which recovered upon 24 h of refeeding in the c-mycfl/fl;Alb-Cre animals.
      There was also no effect of reducing c-myc on recovery of liver mass following
      2/3 partial hepatectomy. CONCLUSIONS: c-Myc appears to be dispensable for normal
      liver growth during the postnatal period, restoration of liver mass following
      partial hepatectomy and recovery from fasting.

PMID- 22397687
TI  - The mGluR5 antagonist AFQ056 does not affect methylation and transcription of the
      mutant FMR1 gene in vitro.
AB  - BACKGROUND: Fragile X syndrome (FXS), the leading cause of inherited mental
      retardation, is due to expansion and methylation of a CGG sequence in the FMR1
      gene, which result in its silencing and consequent absence of FMRP protein. This
      absence causes loss of repression of metabotropic glutamate receptor 5 (mGluR5)
      mediated pathways resulting in the behavioral and cognitive impairments
      associated with FXS. In a randomized, double-blind trial it was recently
      demonstrated a beneficial effect of AFQ056, a selective inhibitor of metabotrobic
      glutamate receptor type 5 (mGluR5), on fully methylated FXS patients respect to
      partially methylated FXS ones. METHODS: To determine whether AFQ056 may have
      secondary effects on the methylation and transcription of FMR1, here we treated
      three FXS lymphoblastoid cell lines and one normal control male line. A
      quantitative RT-PCR was performed to assess transcriptional reactivation of the
      FMR1 gene. To assess the methylation status of the FMR1 gene promoter it was
      carried out a bisulphite sequencing analysis. RESULTS: Both FMR1-mRNA levels and
      DNA methylation were unmodified with respect to untreated controls. CONCLUSIONS:
      These results demonstrate that the AFQ056 effect on fully methylated FXS patients
      is not due to a secondary effect on DNA methylation and consequent
      transcriptional activation of FMR1.

PMID- 22397688
TI  - Direct detection of antibody concentration and affinity in human serum using
      microscale thermophoresis.
AB  - The direct quantification of both the binding affinity and absolute concentration
      of disease-related biomarkers in biological fluids is particularly beneficial for
      differential diagnosis and therapy monitoring. Here, we extend microscale
      thermophoresis to target immunological questions. Optically generated thermal
      gradients were used to deplete fluorescently marked antigens in 2- and 10-fold
      diluted human serum. We devised and validated an autocompetitive strategy to
      independently fit the concentration and dissociation constant of autoimmune
      antibodies against the cardiac beta1-adrenergic receptor related to dilated
      cardiomyopathy. As an artificial antigen, the peptide COR1 was designed to mimic
      the second extracellular receptor loop. Thermophoresis resolved antibody
      concentrations from 2 to 200 nM and measured the dissociation constant as 75 nM.
      The approach quantifies antibody binding in its native serum environment within
      microliter volumes and without any surface attachments. The simplicity of the mix
      and probe protocol minimizes systematic errors, making thermophoresis a promising
      detection method for personalized medicine.

PMID- 22397689
TI  - Sensory threshold of 1,1,6-trimethyl-1,2-dihydronaphthalene (TDN) and
      concentrations in young Riesling and non-Riesling wines.
AB  - 1,1,6-Trimethyl-1,2-dihydronaphthalene (TDN) is well-known to contribute "petrol"
      aromas to aged Riesling wines, but its prevalence and contribution to young
      Riesling or non-Riesling wines is not well understood. TDN concentrations were
      measured in 1-3-year-old varietal wines produced from Cabernet franc (n = 14
      wines), Chardonnay (17), Cabernet Sauvignon (4), Gewurztraminer (4), Merlot (9),
      Pinot gris (6), Pinot noir (9), Riesling (28), or Sauvignon blanc (6). TDN
      concentrations in the Riesling wines, 6.4 +/- 3.8 MUg/L, were significantly
      higher than in all other varietals, 1.3 +/- 0.8 MUg/L. The odor detection
      thresholds for TDN were then determined in both model wine and a neutral white
      wine. Group sensory thresholds were found to be the same in both matrices, 2
      MUg/L, indicating little masking of TDN due to the odorants in the neutral white.
      The TDN sensory threshold was a factor of 10 below the previously reported odor
      threshold. On the basis of this revised threshold, 27 of 28 Riesling wines had
      suprathreshold TDN, whereas only 7 of 69 non-Riesling wines had suprathreshold
      TDN. The monoterpenes linalool and geraniol were also measured in the Riesling
      wines, and odor activity values (OAVs) were calculated for the monoterpenes and
      TDN. The OAV for TDN was higher than for the monoterpenes in 25 of 28 Riesling
      wines.

PMID- 22397691
TI  - Copper-catalyzed coupling of 1,1-dibromo-1-alkenes with phenols: a general,
      modular, and efficient synthesis of ynol ethers, bromo enol ethers, and ketene
      acetals.
AB  - An efficient and general copper-catalyzed method is reported for the synthesis of
      phenol-derived 1-bromoenol ethers, ynol ethers, and ketene acetals by
      chemodivergent copper-catalyzed cross-coupling between readily available 1,1
      dibromo-1-alkenes and phenols.

PMID- 22397690
TI  - Islet protective and insulin secretion property of Murraya koenigii and Ocimum
      tenuflorum in streptozotocin-induced diabetic mice.
AB  - The present study investigates the antidiabetogenic effects of Murraya koenigii
      (L.) Spr. and Ocimum tenuflorum L. on streptozotocin-induced diabetic Swiss mice.
      Treatment with extracts of M. koenigii (chloroform; MKC) and O. tenuflorum
      (aqueous; OTA) resulted in proper glucose utilization with an increase in liver
      glucose-6-phosphate dehydrogenase enzyme activity, and normal glycogenesis in
      hepatic and muscle tissues. Pancreatic and intestinal glucosidase inhibitory
      activity observed with MKC and OTA treatment indicated beneficial effects in
      reducing postprandial hyperglycemia with concomitant improvement in glucose
      metabolism. The glucosidase inhibition was prolonged, even after discontinuation
      of MKC and OTA treatment. Normalization of plasma insulin and C-peptide levels
      was observed in diabetic mice, indicating endogenous insulin secretion after
      treatment. The histochemical and immunohistochemical analysis of pancreatic
      islets suggests the role of MKC and OTA in pancreatic beta-cell protection and
      the functional pancreatic islets that produce insulin. The study demonstrates the
      significance of MKC and OTA in glucosidase inhibition and islet protection in the
      murine diabetic model. These findings suggest the potential of the extracts in
      adjuvant therapy for the treatment of diabetes and the possible development of
      potential neutraceuticals.

PMID- 22397692
TI  - DFT investigation of the molybdenum cofactor in periplasmic nitrate reductases:
      structure of the Mo(V) EPR-active species.
AB  - The periplasmic nitrate reductase NAP belongs to the DMSO reductase family that
      regroups molybdoenzymes housing a bis-molybdopterin cofactor as the active site.
      Several forms of the Mo(V) state, an intermediate redox state in the catalytic
      cycle of the enzyme, have been evidenced by EPR spectroscopy under various
      conditions, but their structure and catalytic relevance are not fully understood.
      On the basis of structural data available from the literature, we built several
      models that reproduce the first coordination sphere of the molybdenum cofactor
      and used DFT methods to make magneto-structural correlations on EPR-detected
      species. "High-g" states, which are the most abundant Mo(V) species, are
      characterized by a low-anisotropy g tensor and a high g(min) value. We assign
      this signature to a six-sulfur coordination sphere in a pseudotrigonal prismatic
      geometry with a partial disulfide bond. The "very high-g" species is well
      described with a sulfido ion as the sixth ligand. The "low-g" signal can be
      successfully associated to a Mo(V) sulfite-oxidase-type active site with only one
      pterin moiety coordinated to the molybdenum ion with an oxo or sulfido axial
      ligand. For all these species we investigate their catalytic activity using a
      thermodynamic point of view on the molybdenum coordination sphere. Beyond the
      periplasmic nitrate reductase case, this work provides useful magneto-structural
      correlations to characterize EPR-detected species in mononuclear molybdoenzymes.

PMID- 22397693
TI  - Self-healing surface hydrophobicity by consecutive release of hydrophobic
      molecules from mesoporous silica.
AB  - The paper reports a novel approach to achieve self-healing surface
      hydrophobicity. Mesoporous silica is used as the reservoir for hydrophobic
      molecules, i.e., octadecylamine (ODA), that can release and refresh the surface
      hydrophobicity consecutively. A polymdopamine layer is used to further
      encapsulate silica-ODA, providing a reactive layer, governing release of the
      underlying ODA, and improving the dispersivity of silica nanoparticles in bulk
      resin. The approach arrives at self-healing (super)hydrophobicity without using
      any fluoro-containing compounds.

PMID- 22397694
TI  - A multi-site study of the feasibility and clinical utility of Goal Attainment
      Scaling in geriatric day hospitals.
AB  - BACKGROUND: Goal Attainment Scaling (GAS) is an individualized goal-setting and
      measurement approach that is useful for patients with multiple, individualized
      health problems, such as those served by geriatric day hospitals (GDHs) and other
      specialized geriatric programmes. PURPOSE: To assess the feasibility and utility
      of GAS in a multi-site study of six GDH affiliated with the Regional Geriatric
      Programmes of Ontario. METHOD: Individualized GAS guides were developed for 15
      consecutively admitted patients at each site [total n = 90; mean age: 76.2 SD
      8.3; 58.9% female; mean attendances: 24.0 SD 10.3]. Staff members (n = 39) were
      surveyed on their experience with GAS. RESULTS: Mean goals/patient ranged across
      sites from 2.1 to 4.3. Mean GAS discharge score was 52.3 SD 8.7, close to the
      theoretically expected values of 50 SD 10. Common goals included mobility,
      community reintegration, basic and instrumental activities of daily living,
      medical issues, cognition/communication, and home safety. Estimated mean time to
      develop a GAS guide ranged across sites from 15.3 to 43.8 min. CONCLUSION:
      Clients were often involved in goal setting; family involvement was less
      frequent. The staff survey identified challenges and benefits regarding the use
      of GAS. Study results are being used to inform a more consistent approach to the
      clinical and research use of GAS in GDH.

PMID- 22397695
TI  - Differential binding between PatS C-terminal peptide fragments and HetR from
      Anabaena sp. PCC 7120.
AB  - Heterocyst differentiation in the filamentous cyanobacterium Anabaena sp. strain
      PCC 7120 occurs at regular intervals under nitrogen starvation and is regulated
      by a host of signaling molecules responsive to availability of fixed nitrogen.
      The heterocyst differentiation inhibitor PatS contains the active pentapeptide
      RGSGR (PatS-5) at its C-terminus considered the minimum PatS fragment required
      for normal heterocyst pattern formation. PatS-5 is known to bind HetR, the master
      regulator of heterocyst differentiation, with a moderate affinity and a
      submicromolar dissociation constant. Here we characterized the affinity of HetR
      for several PatS C-terminal fragments by measuring the relative ability of each
      fragment to knockdown HetR binding to DNA in electrophoretic mobility shift
      assays and using isothermal titration calorimetry (ITC). HetR bound to PatS-6
      (ERGSGR) >30 times tighter (K(d) = 7 nM) than to PatS-5 (K(d) = 227 nM) and >1200
      times tighter than to PatS-7 (DERGSGR) (K(d) = 9280 nM). No binding was detected
      between HetR and PatS-8 (CDERGSGR). Quantitative binding constants obtained from
      ITC measurements were consistent with qualitative results from the gel shift
      knockdown assays. CW EPR spectroscopy confirmed that PatS-6 bound to a MTSL spin
      labeled HetR L252C mutant at a 10-fold lower concentration compared to PatS-5.
      Substituting the PatS-6 N-terminal glutamate to aspartate, lysine, or glycine did
      not alter binding affinity, indicating that neither the charge nor size of the N
      terminal residue's side chain played a role in enhanced HetR binding to PatS-6,
      but rather increased binding affinity resulted from new interactions with the
      PatS-6 N-terminal residue peptide backbone.

PMID- 22397696
TI  - Faidha gani? What's the point: HIV and the logics of (non)-disclosure among young
      activists in Zanzibar.
AB  - Most HIV treatment guidelines advise people who test positive to disclose their
      status to improve adherence and garner psychosocial care and support. Similarly,
      advocacy groups for people living with HIV encourage disclosure as a key
      component of fighting self- and community-based stigma. Although there is
      arguably much to be gained by disclosing, there is also much at stake, including
      issues of individual and family honour and the possibility of living a 'normal'
      life. Starting with the question, Faidha gani? or 'What's the point?' this paper
      attempts to shed light on motives for disclosure and non-disclosure. The
      arguments draw from a qualitative study among young HIV-positive adults in
      eastern Africa and, most specifically, an in-depth case study of one couple in
      Zanzibar.

PMID- 22397697
TI  - N-glycan profiling by microchip electrophoresis to differentiate disease states
      related to esophageal adenocarcinoma.
AB  - We report analysis of N-glycans derived from disease-free individuals and
      patients with Barrett's esophagus, high-grade dysplasia, and esophageal
      adenocarcinoma by microchip electrophoresis with laser-induced fluorescence
      detection. Serum samples in 10 MUL aliquots are enzymatically treated to cleave
      the N-glycans that are subsequently reacted with 8-aminopyrene-1,3,6-trisulfonic
      acid to add charge and a fluorescent label. Separations at 1250 V/cm and over 22
      cm yielded efficiencies up to 700,000 plates for the N-glycans and analysis times
      under 100 s. Principal component analysis (PCA) and analysis of variance (ANOVA)
      tests of the peak areas and migration times are used to evaluate N-glycan
      profiles from native and desialylated samples and determine differences among the
      four sample groups. With microchip electrophoresis, we are able to distinguish
      the three patient groups from each other and from disease-free individuals.

PMID- 22397698
TI  - Hybrid Monte Carlo self-consistent field approach to model a thin layer of a
      polyelectrolyte gel near an adsorbing surface.
AB  - The use of thin layers of a surface bound (polyelectrolyte) hydrogels for
      measuring the concentration of metal ions from electrolyte solutions is our
      motivation for modeling such hydrogels. The gels are composed of polymeric
      species with conformational degrees of freedom on the nanometer scale. The
      polymer conformations are affected by the presence of cross-links in the gel on a
      five to ten times larger length scale, and the repulsive interactions generated
      by the charges along the chains. Here we present a hybrid computational Monte
      Carlo Self-consistent field (MC-SCF) approach to model such hydrogels. The SCF
      formalism is used to evaluate the conformational properties of the chains,
      implementing a freely jointed chain model, in between featureless cross-links.
      The Monte Carlo simulation method is used to sample the (restricted)
      translational degrees of freedom of the cross-links in the gel. We consider the
      case that the polymers in the gel have an affinity for surface positioned at the
      edge of the simulation volume. The polymer density decays as a power-law from the
      surface to the gel-density with an exponent close to -4/3. The gel features
      relatively large density fluctuations which is natural for a gel with a low
      density (phi ~ 0.035), a low degree of cross-linking (average of three chainparts
      per cross-link), and relatively large chains (N = 50) in between the cross-links.
      Some parts of the gel can break loose from the gel and sample the adjoining
      volume. Representative snapshots exemplify large density fluctuations, which
      explain the large pore size distribution observed in experimental counterparts.

PMID- 22397699
TI  - Measurement of radionuclides and absorbed dose rates in soil samples of Peshawar,
      Pakistan, using gamma ray spectrometry.
AB  - The analysis of gamma-emitting radionuclides in nature, i.e. (226)Ra, (232)Th,
      (40)K and (137)Cs, has been carried out in soil samples collected from Peshawar
      University Campus and surrounding areas using a high purity germanium detector
      coupled with a computer-based high-resolution multichannel analyser. The activity
      concentrations in soil ranged from 30.20+/-0.65 to 61.90+/-0.95, 50.10+/-0.54 to
      102.80+/-1.04, 373.60+/-4.56 to 1082+/-11.38 and 9.50+/-0.11 to 46.60+/-0.42 Bq
      kg(-1) for (226)Ra, (232)Th, (40)K and (137)Cs, with a mean value of 45+/-7.70,
      67+/-12.50, 878+/-180 and 19+/-9.20 Bq kg(-1), respectively. The radium
      equivalent activity, internal and external hazard indices have mean values of
      203.40+/-29.40 Bq kg(-1), 0.56 and 0.68, respectively. The mean values of outdoor
      and indoor absorbed dose rates in air and the annual effective dose equivalents
      were found to be 106.50 and 128 nGy h(-1) and 0.19 and 0.54 mSv y(-1),
      respectively. In the present study, (40)K was the major radionuclide present in
      soil samples. The presence of (137)Cs indicates that this area also received some
      fallout from the nuclear accident of the Chernobyl power plant in 1986. The
      activity concentrations of radionuclides found in soil samples during the current
      investigation were nominal. Therefore, they are not associated with any potential
      source of health hazard to the public.

PMID- 22397700
TI  - Factors associated with initiation of antihyperglycaemic medication in UK
      patients with newly diagnosed type 2 diabetes.
AB  - AIM: To assess the factors associated with antihyperglycaemic medication
      initiation in UK patients with newly diagnosed type 2 diabetes. METHODS: In a
      retrospective cohort study, patients with newly diagnosed type 2 diabetes were
      identified during the index period of 2003-2005. Eligible patients were >= 30
      years old at the date of the first observed diabetes diagnosis (referred to as
      index date) and had at least 2 years of follow-up medical history (N = 9,158).
      Initiation of antihyperglycaemic medication (i.e., treatment) was assessed in the
      2-year period following the index date. Adjusted Cox regression models were used
      to examine the association between time to medication initiation and patient age
      and other factors. RESULTS: Mean (SD) HbA1c at diagnosis was 8.1% (2.3). Overall,
      51% of patients initiated antihyperglycaemic medication within 2 years (65%, 55%,
      46% and 40% for patients in the 30- < 45, 45- < 65, 65- < 75, 75+ age groups,
      respectively). Among the treated patients, median (25th, 75th percentile) time to
      treatment initiation was 63 (8, 257) days. Of the patients with HbA1c >= 7.5% at
      diagnosis, 87% initiated treatment within 2 years. These patients with a higher
      HbA1c also had shorter time to treatment initiation (adjusted hazard ratio (HR) =
      2.44 [95% confidence interval (CI): 1.61, 3.70]; p < 0.0001). Increasing age (in
      years) was negatively associated with time to treatment initiation (HR = 0.98
      [95% CI: 0.97, 0.99]; p < 0.001). Factors significantly associated with shorter
      time to treatment initiation included female gender and use of cardiovascular
      medications at baseline or initiated during follow up. CONCLUSIONS: In this UK
      cohort of patients with newly diagnosed type 2 diabetes, only 51% had
      antihyperglycaemic medication initiated over a 2-year period following diagnosis.
      Older patients were significantly less likely to have been prescribed
      antihyperglycaemic medications. Elevated HbA1c was the strongest factor
      associated with initiating antihyperglycaemic medication in these patients.

PMID- 22397701
TI  - Transfection of naked nuclear factor-kappaB decoy oligodeoxynucleotides into
      liver by rapid portal vein infusion in rats: its effect on ischemia-reperfusion
      injury of liver.
AB  - This study was aimed at examining whether rapid portal vein infusion (RPVI) of a
      small volume of naked oligodeoxynucleotides (ODNs) could be used to transfect
      sufficient amounts of nuclear factor-kappaB (NF-kappaB) decoy ODN into the liver
      to suppress NF-kappaB activation during liver ischemia-reperfusion (I/R) injury,
      in which NF-kappaB plays a central role in regulating the production of
      inflammatory cytokines. One milliliter of naked NF-kappaB decoy ODN solution was
      administered into the portal vein for a few seconds. Transfection efficacy was
      examined by labeling the ODN with a fluorescent tag. Activation of NF-kappaB was
      investigated by electrophoretic mobility shift assay. Levels of serum liver
      enzymes and cytokines were measured during liver I/R injury. NF-kappaB decoy ODN
      was preferentially incorporated into Kupffer cells and sinusoidal endothelial
      cells, but not hepatocytes, in the rat liver. Transfected NF-kappaB decoy ODN
      suppressed the function of NF-kappaB in both Kupffer cells and sinusoidal
      endothelial cells during liver I/R injury, causing significant decreases in serum
      tumor necrosis factor-alpha and interleukin-6 levels 3 hr after reperfusion.
      Although the decrease in serum liver enzymes was not significant, naked NF-kappaB
      decoy ODN was successfully incorporated into Kupffer cells and sinusoidal
      endothelial cells by rapid portal vein infusion, inhibited NF-kappaB activation
      in both cells, and suppressed the production of inflammatory cytokines during the
      early phase of liver I/R injury.

PMID- 22397702
TI  - Conserved phosphoryl transfer mechanisms within kinase families and the role of
      the C8 proton of ATP in the activation of phosphoryl transfer.
AB  - BACKGROUND: The kinome is made up of a large number of functionally diverse
      enzymes, with the classification indicating very little about the extent of the
      conserved kinetic mechanisms associated with phosphoryl transfer. It has been
      demonstrated that C8-H of ATP plays a critical role in the activity of a range of
      kinase and synthetase enzymes. RESULTS: A number of conserved mechanisms within
      the prescribed kinase fold families have been identified directly utilizing the
      C8-H of ATP in the initiation of phosphoryl transfer. These mechanisms are based
      on structurally conserved amino acid residues that are within hydrogen bonding
      distance of a co-crystallized nucleotide. On the basis of these conserved
      mechanisms, the role of the nucleotide C8-H in initiating the formation of a
      pentavalent intermediate between the gamma-phosphate of the ATP and the substrate
      nucleophile is defined. All reactions can be clustered into two mechanisms by
      which the C8-H is induced to be labile via the coordination of a backbone
      carbonyl to C6-NH2 of the adenyl moiety, namely a "push" mechanism, and a "pull"
      mechanism, based on the protonation of N7. Associated with the "push" mechanism
      and "pull" mechanisms are a series of proton transfer cascades, initiated from C8
      H, via the tri-phosphate backbone, culminating in the formation of the
      pentavalent transition state between the gamma-phosphate of the ATP and the
      substrate nucleophile. CONCLUSIONS: The "push" mechanism and a "pull" mechanism
      are responsible for inducing the C8-H of adenyl moiety to become more labile.
      These mechanisms and the associated proton transfer cascades achieve the proton
      transfer via different family-specific conserved sets of amino acids. Each of
      these mechanisms would allow for the regulation of the rate of formation of the
      pentavalent intermediate between the ATP and the substrate nucleophile.
      Phosphoryl transfer within kinases is therefore a specific event mediated and
      regulated via the coordination of the adenyl moiety of ATP and the C8-H of the
      adenyl moiety.

PMID- 22397704
TI  - Comparative molecular dynamics simulation study of crystal environment effect on
      protein structure.
AB  - Crystal structures of proteins are under the influence from the crystal
      environment. In this study, we used molecular dynamics (MD) simulations to
      explore the possibility of eliminating the effect of the crystal packing and
      recovering the structure in solution. Ten representative proteins were chosen
      from the Protein Structural Change Database as the target systems, and 50 ns MD
      stimulations starting from two crystal structures having different domain
      arrangements were performed for each. The MD trajectories of the relaxation
      processes upon the release from the crystal environment revealed that the
      behaviors of the proteins were classified into three groups: "single domain
      linker", "harmonic motion", and "large barrier". We discuss the structural
      features common to the proteins in each group.

PMID- 22397703
TI  - L-alanyl-L-glutamine ingestion maintains performance during a competitive
      basketball game.
AB  - BACKGROUND: The purpose of this study was to examine the efficacy of L-alanyl-L
      glutamine (AG) ingestion on basketball performance, including jump power,
      reaction time, shooting accuracy and fatigue. METHODS: Ten women (21.2 +/- 1.6
      years; height: 177.8 +/- 8.7 cm; body mass: 73.5 +/- 8.0 kg), all scholarship
      NCAA Division I basketball players, volunteered for this study. Subjects
      participated in four trials, each consisting of a 40-min basketball game with
      controlled time-outs for rehydration. During the first trial (DHY) subjects were
      not allowed to rehydrate, and the total weight lost during the contest was used
      to determine fluid replenishment during the subsequent three trials. During one
      trial subjects consumed only water (W), while during the other two trials
      subjects consumed the AG supplement mixed in water using either a low dose (1 g
      per 500 ml) (AG1) or high dose (2 g per 500 ml) (AG2) concentration. All data
      assessed prior to and following each game were converted into a Delta score (Post
      results - Pre results). All performance data were then analyzed using a one-way
      repeated measures analysis of variance. RESULTS: During DHY subjects lost 1.72 +/
      0.42 kg (2.3%) of their body mass. No differences in fluid intake (1.55 +/- 0.43
      L) were seen between rehydration trials. A 12.5% (p = 0.016) difference in
      basketball shooting performance was noted between DHY and AG1 and an 11.1% (p =
      0.029) difference was seen between AG1 and W. Visual reaction time was
      significantly greater following AG1 (p = 0.014) compared to DHY. Differences (p =
      0.045) in fatigue, as determined by player loads, were seen only between AG2 and
      DHY. No differences were seen in peak or mean vertical jump power during any
      trial. CONCLUSION: Rehydration with AG appears to maintain basketball skill
      performance and visual reaction time to a greater extent than water only.

PMID- 22397705
TI  - Comparison of the behavior of metal-organic frameworks and zeolites for
      hydrocarbon separations.
AB  - The objective of this work was to study the adsorption and separation of the most
      important families of hydrocarbon compounds on metal-organic frameworks (MOFs),
      in comparison with zeolites. For this purpose, we have selected four probe
      molecules, each of them representing one of these families, i.e., o- and p-xylene
      as aromatics, 1-octene as an alkene, and n-octane as an alkane. The separation of
      these four molecules was studied by binary breakthrough experiments. To represent
      the large diversity of MOF structures, the experiments were carried out with (i)
      two MOFs with coordinatively unsaturated metal sites (CUS), i.e., Cu-btc (HKUST
      1) and CPO-27-Ni, (ii) a MOF with an anionic framework and extraframework
      cations, i.e. RHO-ZMOF, and (iii) two rather apolar zeolitic imidazolate
      framework (ZIF) materials with different pore sizes, i.e. ZIF-8 and ZIF-76.
      Zeolite NaY and zeolite beta were used as polar and apolar reference adsorbents,
      respectively. The results can be briefly summarized as follows: ZIFs (not
      carrying any polar functional groups) behave like apolar adsorbents and exhibit
      very interesting and unexpected molecular sieving properties. CUS-MOFs behave
      like polar adsorbents but show the specificity of preferring alkenes over
      aromatics. This feature is rationalized thanks to DFT+D calculations. MOFs with
      extraframework cations behave like polar (cationic) zeolites.

PMID- 22397706
TI  - Synthesis of new trisulfonated calix[4]arenes functionalized at the upper rim,
      and their complexation with the trimethyllysine epigenetic mark.
AB  - A synthetic route to produce a new family of trisulfonated calix[4]arenes bearing
      a single group, selectively introduced, that lines the binding pocket is
      reported. Ten examples, including new sulfonamide and biphenyl-substituted hosts,
      each with additional binding elements, demonstrate the tuning of guest affinities
      and selectivities. NMR titrations in phosphate-buffered water show that one of
      the new hosts binds to the modified amino acid trimethyllysine with the highest
      affinity and selectivity observed to date.

PMID- 22397708
TI  - Structurally diverse copper(II) complexes of polyaza ligands containing 1,2,3
      triazoles: site selectivity and magnetic properties.
AB  - Copper(II) acetate mediated coupling reactions between 2,6
      bis(azidomethyl)pyridine or 2-picolylazide and two terminal alkynes afford 1,2,3
      triazolyl-containing ligands L(1)-L(6). These ligands contain various nitrogen
      based Lewis basic sites including two different pyridyls, two nitrogen atoms on a
      1,2,3-triazolyl ring, and the azido group. A rich structural diversity, which
      includes mononuclear and dinuclear complexes as well as one-dimensional polymers,
      was observed in the copper(II) complexes of L(1)-L(6). The preference of
      copper(II) to two common bidentate 1,2,3-triazolyl-containing coordination sites
      was investigated using isothermal titration calorimetry and, using zinc(II) as a
      surrogate, in (1)H NMR titration experiments. The magnetic interactions between
      the copper(II) centers in three dinuclear complexes were analyzed via temperature
      dependent magnetic susceptibility measurements and high-frequency electron
      paramagnetic resonance spectroscopy. The observed magnetic superexchange is
      strongly dependent on the orientation of magnetic orbitals of the copper(II) ions
      and can be completely turned off if these orbitals are arranged orthogonal to
      each other. This work demonstrates the versatility of 1,2,3-triazolyl-containing
      polyaza ligands in forming metal coordination complexes of a rich structural
      diversity and interesting magnetic properties.

PMID- 22397709
TI  - Rhythmic 24-hour variations of frequently used clinical biochemical parameters in
      healthy young males--the Bispebjerg study of diurnal variations.
AB  - PURPOSE: To evaluate the influence of time of day on the circulating
      concentrations of 14 frequently used clinical biochemical parameters in the
      Bispebjerg study of diurnal variations. MATERIALS AND METHODS: Venous blood
      samples were obtained under controlled environmental, activities and food
      conditions from 24 healthy young men every third hour through 24 hours, nine time
      points in total. At each time point, the parameters' concentrations were
      measured. The data were analyzed by rhythmometric statistical methods and in
      addition the biological variations were calculated. RESULTS: Significant
      oscillation of melatonin with an amplitude (amp) of 19.84 pg/ml and a peak at
      03:34 h confirmed the normal 24-hour rhythms of the participants. Potassium (p <
      0.0001, amp = 0.18 mmol/L), sodium (p < 0.0001, amp = 1.10 mmol/L) creatine
      kinase (p = 0.01, amp = 17.18 U/L), bilirubin (p < 0.0001, amp = 2.36 MUmol/L)
      and aspartate aminotransferase (p < 0.0001, amp = 1.66 U/L) oscillated with
      gradually falling mean concentrations through the day to nadir around midnight.
      Urea nitrogen (p = 0.01, amp = 0.22 mmol/L) oscillated with gradually increasing
      mean concentrations through the day peaking around midnight. Lactate
      dehydrogenase (p < 0.0001, amp = 9.76 U/L) oscillated with gradually increasing
      concentrations through the early day peaking in the afternoon. Uric acid (p =
      0.03, amp = 0.013 mmol/L) oscillated with gradually increasing concentrations
      through the night peaking in the morning. Potassium and sodium had the highest 24
      hour oscillations in proportion to the reference intervals of the parameters for
      healthy young men. CONCLUSIONS: In the clinical setting, diurnal variations of
      clinical biochemical parameters commonly used through the day and night must be
      considered when concentration changes in the parameters are evaluated especially
      potassium and sodium.

PMID- 22397707
TI  - Clinical correlates of grey matter pathology in multiple sclerosis.
AB  - Traditionally, multiple sclerosis has been viewed as a disease predominantly
      affecting white matter. However, this view has lately been subject to numerous
      changes, as new evidence of anatomical and histological changes as well as of
      molecular targets within the grey matter has arisen. This advance was driven
      mainly by novel imaging techniques, however, these have not yet been implemented
      in routine clinical practice. The changes in the grey matter are related to
      physical and cognitive disability seen in individuals with multiple sclerosis.
      Furthermore, damage to several grey matter structures can be associated with
      impairment of specific functions. Therefore, we conclude that grey matter damage 
      global and regional - has the potential to become a marker of disease activity,
      complementary to the currently used magnetic resonance markers (global brain
      atrophy and T2 hyperintense lesions). Furthermore, it may improve the prediction
      of the future disease course and response to therapy in individual patients and
      may also become a reliable additional surrogate marker of treatment effect.

PMID- 22397710
TI  - Effects of elastic-band exercise on lower-extremity function among female
      patients with osteoarthritis of the knee.
AB  - OBJECTIVE: To investigate a new style of resistance exercise using elastic bands
      and explore its therapeutic effect on the lower-extremity function of female
      patients with osteoarthritis (OA) of the knee. DESIGN: A randomized, controlled
      clinical trial. SETTING: University-affiliated medical center. PARTICIPANTS:
      Forty-one women with mild-to-moderate knee OA were randomly assigned to one of
      two groups, an exercise group (n = 24; age: 65.0 +/- 8.4 years), and a control
      group (n = 17; age: 70.8 +/- 8.4 years). INTERVENTIONS: The exercise group
      performed supervised exercise with elastic bands in addition to conventional
      modality treatments two to three times a week for 8 weeks. The control group
      received only the conventional modality treatments over the same period. MAIN
      OUTCOME MEASURES: The distance of the functional forward-reach, 30 s chair stand
      repetitions, walking function (time of a 10 m walk, timed up-and-go, and going up
      and-down 13-stair tests), and Western Ontario and McMaster Universities
      Osteoarthritis (WOMAC) index scores. RESULTS: Statistically significant
      improvements in all measures were observed in the exercise group after 8 weeks (p
      < 0.001). Except for the outcomes on the functional forward-reach (p = 0.108) and
      going up-and-down 13-stair test (p = 0.278), there were significant differences
      in the extent of improvement between the two groups. Positive changes in the 30 s
      chair stand test, 10 m walk test, and timed up-and-go test were 2.5 +/- 1.4
      repetitions, 1.4 +/- 1.2 s, and 1.6 +/- 1.1 s in the exercise group, which were
      significant better than those in the control group (0.6 +/- 0.9 repetitions, 0.5
      +/- 1.1 s, and 0.3 +/- 1.1 s, respectively) (p <= 0.001). The lower scores of all
      three subscales of the WOMAC index were significant after 8 weeks (p <= 0.05),
      especially for pain (-2.3 +/- 1.3) and physical function (-10.7 +/- 5.9) (both p
      <= 0.01), and the improvements were all significant better than those of the
      control group (p <= 0.05). CONCLUSIONS: A new style of resistance exercise using
      elastic bands with four color combinations (yellow-red, red-red, red-green, and
      green-green) over a period of 8 weeks can significantly improve lower-extremity
      function among females with mild-to-moderate knee OA.

PMID- 22397712
TI  - A new podapolipid species (Acari) on Scarabaeus (Scarabaeus) acuticollis
      (Insecta: Coleoptera: Scarabaeidae) from Iran.
AB  - A new species of mites of the genus Tarsopolipus (Acari: Prostigmata:
      Podapolipidae) is described from southern Iran. Tarsopolipus husbandi Mortazavi
      and Hajiqanbar n. sp. is a sub-elytral ectoparasite of the scarabaeid beetle,
      Scarabaeus (Scarabaeus) acuticollis. The new species is closely related to
      Tarsopolipus corrugatus Berlese 1911, but is distinguished from it by the
      following characters. Adult female: presence of vestigial setae v(2) and shorter
      setae sc(2). Adult male: presence of setae v' on tibia IV and shorter setae sc(2)
      and c(2). Larval female: shorter cheliceral stylets and longer distance between
      setae v(1) and ch. Species of Tarsopolipus are currently distributed in Afro
      tropical, Palaearctic, and Oriental regions and parasitize species in 3 genera of
      scarabaeid beetles, i.e., Scarabaeus , Kheper, and Drepanopodes, all belonging to
      the tribe Scarabaeini.

PMID- 22397711
TI  - Toxoplasma gondii profilin acts primarily to sequester G-actin while formins
      efficiently nucleate actin filament formation in vitro.
AB  - Apicomplexan parasites employ gliding motility that depends on the polymerization
      of parasite actin filaments for host cell entry. Despite this requirement,
      parasite actin remains almost entirely unpolymerized at steady state; formation
      of filaments required for motility relies on a small repertoire of actin-binding
      proteins. Previous studies have shown that apicomplexan formins and profilin
      exhibit canonical functions on heterologous actins from higher eukaryotes;
      however, their biochemical properties on parasite actins are unknown. We
      therefore analyzed the impact of T. gondii profilin (TgPRF) and FH1-FH2 domains
      of two formin isoforms in T. gondii (TgFRM1 and TgFRM2) on the polymerization of
      T. gondii actin (TgACTI). Our findings based on in vitro assays demonstrate that
      TgFRM1-FH1-FH2 and TgFRM2-FH1-FH2 dramatically enhanced TgACTI polymerization in
      the absence of profilin, making them the sole protein factors known to initiate
      polymerization of this normally unstable actin. In addition, T. gondii formin
      domains were shown to both initiate polymerization and induce bundling of TgACTI
      filaments; however, they did not rely on TgPRF for these activities. In contrast,
      TgPRF sequestered TgACTI monomers, thus inhibiting polymerization even in the
      presence of formins. Collectively, these findings provide insight into the
      unusual control mechanisms of actin dynamics within the parasite.

PMID- 22397713
TI  - Antimicrobial activity of sesquiterpene lactones isolated from traditional
      medicinal plant, Costus speciosus (Koen ex.Retz.) Sm.
AB  - BACKGROUND: Costus speciosus (Koen ex.Retz.) Sm (Costaceae) is an Indian
      ornamental plant which has long been used medicinally in traditional systems of
      medicine. The plant has been found to possess diverse pharmacological activities.
      Rhizomes are used to treat pneumonia, rheumatism, dropsy, urinary diseases,
      jaundice, skin diseases and leaves are used to treat mental disorders. METHOD:
      Antibacterial and antifungal activities were tested using Disc diffusion method
      and Minimum Inhibitory Concentration (MIC). Column chromatography was used to
      isolate compounds from hexane extract. X-ray crystallography technique and GC-MS
      analysis were used to identify the compounds RESULTS: Antibacterial and
      antifungal activities were observed in hexane, chloroform, ethyl acetate and
      methanol extracts. Hexane extract of C.speciosus showed good activity against
      tested fungi also. Two sesquiterpenoid compounds were isolated (costunolide and
      eremanthin) from the hexane extract. Both the compounds did not inhibit the
      growth of tested bacteria. But, both the compounds inhibited the tested fungi.
      The compound costunolide showed significant antifungal activity. The MIC values
      of costunolide were; 62.5 MUg/ml against Trichophyton mentagrophytes, 62. MUg/ml
      against T. simii, 31.25 MUg/ml against T. rubrum 296, 62.5 MUg/ml against T.
      rubrum 57, 125 MUg/ml against Epidermophyton floccosum, 250 MUg/ml against
      Scopulariopsis sp, 250 MUg/ml against Aspergillus niger, 125 MUg/ml against
      Curvulari lunata, 250 MUg/ml against Magnaporthe grisea. CONCLUSION: Hexane
      extract showed promising antibacterial and antifungal activity. The isolated
      compound costunolide showed good antifungal activity.

PMID- 22397716
TI  - Fe-catalyzed allylic C-C-bond activation: vinylcyclopropanes as versatile
      a1,a3,d5-synthons in traceless allylic substitutions and [3 + 2]-cycloadditions.
AB  - The low-valent iron complex Bu(4)N[Fe(CO)(3)(NO)] (TBAFe) catalyzes the allylic C
      C-bond activation of electron-poor vinyl cyclopropanes to generate synthetically
      useful a1,a3,d5-synthons which are prone to undergo multiple consecutive
      reactions. The versatility of this approach is demonstrated by a traceless
      allylic substitution and a formal [3 + 2] cycloaddition to give either
      functionalized acyclic products or densely substituted cyclopentanes and
      pyrrolidines in high yields and regioselectivities.

PMID- 22397714
TI  - Estimating phospholipid membrane-water partition coefficients using comprehensive
      two-dimensional gas chromatography.
AB  - Recent studies have shown that membrane-water partition coefficients of organic
      chemicals can be used to predict bioaccumulation and type I narcosis toxicity
      more accurately than the traditional K(OW)-based approach. In this paper, we
      demonstrate how comprehensive two-dimensional gas chromatography (GC * GC) can be
      used to estimate such membrane-water partition coefficients (K(PLW)s), focusing
      in particular on phosphatidyl choline based lipids. This method performed well
      for a set of 38 compounds, including polycyclic aromatic hydrocarbons,
      polychlorinated benzenes and biphenyls, and substituted benzenes including some
      phenols and anilines. The average difference between the estimated and the
      measured log K(PLW) values of 0.47 log units is smaller than in the case of a log
      K(OW) correlation approach but larger than seen using a polyparameter linear free
      energy relationship based approach. However, the GC * GC based method presents
      the advantage that it can be applied to mixtures of chemicals that are not
      completely identified, such as petroleum hydrocarbon mixtures. At the same time,
      our application of the GC * GC method suffered larger errors when applied to
      certain hydrogen bonding compounds due to the inability of the GC * GC capillary
      columns phases that we used to interact with analytes via hydrogen bond
      donation/electron acceptance.

PMID- 22397717
TI  - Vinylidene-quinone methides, photochemical generation and beta-silicon effect on
      reactivity.
AB  - Irradiation of 2-alkynylphenols resulted in the generation of vinylidene-quinone
      methides (QMs), which were detected by laser flash photolysis in organic solvents
      and aqueous acetonitrile. QMs' spectroscopic properties and electrophilicity were
      both significantly affected by beta-silicon effect. The hydration of the alkynyl
      moiety (22 and 900 M(-1) s(-1)for QM-1 and QM-2, in aqueous acetonitrile) was an
      acid- and base-catalyzed process. The addition of amines was fast (9.2 * 10(3) M(
      1) s(-1) < k(2) < 1.3 * 10(8) M(-1) s(-1)), yielding ketimines, with primary
      amines.

PMID- 22397715
TI  - Treatment of a solid tumor using engineered drug-resistant immunocompetent cells
      and cytotoxic chemotherapy.
AB  - Multimodal therapy approaches, such as combining chemotherapy agents with
      cellular immunotherapy, suffers from potential drug-mediated toxicity to immune
      effector cells. Overcoming such toxic effects of anticancer cellular products is
      a potential critical barrier to the development of combined therapeutic
      approaches. We are evaluating an anticancer strategy that focuses on overcoming
      such a barrier by genetically engineering drug-resistant variants of
      immunocompetent cells, thereby allowing for the coadministration of cellular
      therapy with cytotoxic chemotherapy, a method we refer to as drug-resistant
      immunotherapy (DRI). The strategy relies on the use of cDNA sequences that confer
      drug resistance and recombinant lentiviral vectors to transfer nucleic acid
      sequences into immunocompetent cells. In the present study, we evaluated a DRI
      based strategy that incorporates the immunocompetent cell line NK-92, which has
      intrinsic antitumor properties, genetically engineered to be resistant to both
      temozolomide and trimetrexate. These immune effector cells efficiently lysed
      neuroblastoma cell lines, which we show are also sensitive to both chemotherapy
      agents. The antitumor efficacy of the DRI strategy was demonstrated in vivo,
      whereby neuroblastoma-bearing NOD/SCID/gamma-chain knockout (NSG) mice treated
      with dual drug-resistant NK-92 cell therapy followed by dual cytotoxic
      chemotherapy showed tumor regression and significantly enhanced survival compared
      with animals receiving either nonengineered cell-based therapy and chemotherapy,
      immunotherapy alone, or chemotherapy alone. These data show there is a benefit to
      using drug-resistant cellular therapy when combined with cytotoxic chemotherapy
      approaches.

PMID- 22397718
TI  - Chemo-immunotherapy dosing in older patients with diffuse large B-cell lymphoma:
      is this how we should treat our parents?

PMID- 22397719
TI  - Expansion of effector T cells associated with decreased PD-1 expression in
      patients with indolent B cell lymphomas and chronic lymphocytic leukemia.
AB  - In patients with chronic lymphocytic leukemia (CLL), numbers of CD8 + CD45RA +/-
      CD27- effector T cells are expanded. We investigated whether this expansion is
      also present in other B cell malignancies and the possible mechanism underlying
      these changes. Whereas an increase in total CD4+and CD8+ T cell numbers was found
      only in CLL, numbers of CD4+ and CD8+ effector T cells were significantly
      increased in both CLL and indolent lymphoma, but not aggressive lymphoma and
      myeloma. Interestingly, PD-1 expression was decreased on effector T cells and
      inversely correlated with effector T cell numbers, suggesting a functional role
      for PD-1 in regulating T cell homeostasis. In vitro experiments revealed impaired
      up-regulation of PD-1 upon T cell activation in the presence of malignant but
      also healthy B cells. Our data suggest that in CLL and indolent lymphoma, the
      malignant B cells affect PD-1 expression on effector T cells, resulting in an
      expansion of these subsets.

PMID- 22397720
TI  - Cigarette smoking is associated with a small increase in the incidence of non
      Hodgkin lymphoma: a meta-analysis of 24 observational studies.
AB  - Previous studies have evaluated the association between cigarette smoking and
      incidence of non-Hodgkin lymphoma (NHL) with inconclusive results. Our main
      objective was to evaluate this relationship using a meta-analysis of
      observational studies. A literature search was undertaken through October 2011
      looking for pertinent studies. Seven prospective cohort and 17 case-control
      studies were included in this meta-analysis. Outcomes were calculated using the
      random-effects model and are reported as odds ratio (OR). Meta-regression was
      used to evaluate the dose-response of intensity and duration of smoking in NHL
      incidence. Our study found an OR of 1.40 (95% confidence interval [CI] 1.14-1.73;
      p = 0.001) in current female smokers seen only in case-control studies. No
      increased odds of NHL was seen in men. There was no association between smoking
      and the most common NHL subtypes, with the exception of a statistical trend
      toward a higher incidence of T-cell lymphoma. In conclusion, there appears to be
      an increase in the odds of NHL in current female smokers.

PMID- 22397721
TI  - Association between polymorphic sites in thymidylate synthase gene and risk of
      non-Hodgkin lymphoma: a systematic review and pooled analysis.
AB  - Epidemiological studies have evaluated the association between polymorphic sites
      in the thymidylate synthase (TYMS) gene and non-Hodgkin lymphoma (NHL) risk, but
      the results remain controversial. Here we performed a meta-analysis to estimate
      the relationship between TYMS polymorphisms and the risk of NHL and two of its
      subtypes from all nine published case-control studies. Our meta-analysis
      suggested that both 1053C > T and IVS6-68C >T polymorphisms were significantly
      associated with decreased risks of NHL among Caucasians (for 1053C > T: TT vs.
      CC, odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.64-0.95; recessive
      model, OR = 0.81, 95% CI = 0.67-0.98 and for IVS6 - 68C > T: TT vs. CC, OR =
      0.61, 95% CI = 0.40-0.92; recessive model, OR = 0.63, 95% CI = 0.42-0.93),
      whereas the TSER, 1122A > G and 1494del6 polymorphisms had no influence on the
      susceptibility to NHL. Further analysis revealed that the T allele of the 1053C >
      T polymorphism might provide protective effects in Caucasians against the risk of
      NHL (OR = 0.90, 95% CI = 0.82-0.98) and follicular lymphoma (FL) (OR = 0.81, 95%
      CI = 0.71-0.93), but not diffuse large B-cell lymphoma (DLBCL). Additionally, the
      IVS6 - 68C > T variant homozygote genotype was significantly associated with
      reduced risks for DLBCL (TT vs. CC: OR = 0.51, 95% CI = 0.28-0.94; recessive
      model: OR = 0.53, 95% CI = 0.29-0.96), but not FL. However, individuals carrying
      the T allele of the IVS6 - 68C > T polymorphism were not significantly associated
      with reduced risks for DLBCL and FL.

PMID- 22397722
TI  - CCL2 and CXCL2 enhance survival of primary chronic lymphocytic leukemia cells in
      vitro.
AB  - Chronic lymphocytic leukemia (CLL) is predominantly a disease of accumulation
      rather than rapid proliferation. To date, no cell lines exist, as CLL cells
      undergo rapid apoptosis when cultured in vitro, suggesting that a favorable in
      vivo microenvironment is required. To identify survival signals we cultured
      primary CLL peripheral blood mononuclear cells (PBMCs) at high density, which has
      previously been shown to dramatically improve survival. Using antibody arrays we
      measured the level of 42 cytokines in culture supernatants and showed that
      inerleukin-6 (IL-6), IL-8, CXCL2 and CCL2 were highly up-regulated in culture.
      This is the first report to describe a role for CCL2 and CXCL2 in CLL cell
      survival. Importantly, CXCL2, IL-6 and IL-8 were significantly up-regulated in
      primary patient plasma. The addition of either CXCL2 or CCL2 enhanced CLL cell
      survival, while antibodies blocking these chemokines reduced survival. Co-culture
      of CLL cells and PBMC accessory cells separated by transwells provided a similar
      degree of survival protection compared to normal culture, whereas CLL cells
      cultured alone died rapidly. Interestingly, CCL2 and CXCL2 appeared to be
      produced by CLL cells but only when co-cultured with accessory cells. Thus, we
      speculate that accessory cells release soluble factors that promote the
      production of these pro-survival chemokines from CLL cells and physical
      interactions are not required. Our data support the concept that the CLL
      microenvironment is critical, and suggests that soluble factors are more
      important than physical interactions.

PMID- 22397723
TI  - Multiple myeloma and immunomodulation: regulating the regulatory cells.

PMID- 22397724
TI  - Local control of the cis-trans isomerization and backbone dihedral angles in
      peptides using trifluoromethylated pseudoprolines.
AB  - NMR studies and theoretical calculations have been performed on model peptides Ac
      Ser(PsiPro)-NHMe, (S,S)Ac-Ser(Psi(H,CF3)Pro)-NHMe, and (R,S)Ac-Ser(Psi(CF3,H)Pro)
      NHMe. Their thermodynamic and kinetic features have been analyzed in chloroform,
      DMSO, and water, allowing a precise description of their conformational
      properties. We found that trifluoromethyl C(delta)-substitutions of oxazolidine
      based pseudoprolines can strongly influence the cis-trans rotational barriers
      with only moderate effects on the cis/trans population ratio. In CHCl(3), the
      configuration of the CF(3)-C(delta) entirely controls the psi-dihedral angle,
      allowing the stabilization of gamma-turn-like or PPI/PPII-like backbone
      conformations. Moreover, in water and DMSO, this C(delta)-configuration can be
      used to efficiently constrain the ring puckering without affecting the cis/trans
      population ratio. Theoretical calculations have ascertained the electronic and
      geometric properties induced by the trifluoromethyl substituent and provided a
      rational understanding of the NMR observations.

PMID- 22397725
TI  - Hemiazygos vein "steal hypoxic-syndrome" after hemi-Fontan operation:
      comprehensive four-dimensional flow magnetic resonance visualisation.
AB  - A 2-year-old boy with hypoplastic left heart syndrome and previous hemi-Fontan
      palliation surgery was referred for cardiovascular magnetic resonance evaluation
      because of progressive cyanosis. This case report illustrates the advantages of
      non-invasive four-dimensional magnetic resonance imaging for comprehensive
      identification and quantification of venovenous collaterals in patients with
      palliated hemi-Fontan staged surgery.

PMID- 22397726
TI  - Insecticide resistance in the sand fly, Phlebotomus papatasi from Khartoum State,
      Sudan.
AB  - BACKGROUND: Phlebotomus papatasi the vector of cutaneous leishmaniasis (CL) is
      the most widely spread sand fly in Sudan. No data has previously been collected
      on insecticide susceptibility and/or resistance of this vector, and a first study
      to establish a baseline data is reported here. METHODS: Sand flies were collected
      from Surogia village, (Khartoum State), Rahad Game Reserve (eastern Sudan) and
      White Nile area (Central Sudan) using light traps. Sand flies were reared in the
      Tropical Medicine Research Institute laboratory. The insecticide susceptibility
      status of first progeny (F1) of P. papatasi of each population was tested using
      WHO insecticide kits. Also, P. papatasi specimens from Surogia village and Rahad
      Game Reserve were assayed for activities of enzyme systems involved in
      insecticide resistance (acetylcholinesterase (AChE), non-specific
      carboxylesterases (EST), glutathione-S-transferases (GSTs) and cytochrome p450
      monooxygenases (Cyt p450). RESULTS: Populations of P. papatasi from White Nile
      and Rahad Game Reserve were sensitive to dichlorodiphenyltrichloroethane (DDT),
      permethrin, malathion, and propoxur. However, the P. papatasi population from
      Surogia village was sensitive to DDT and permethrin but highly resistant to
      malathion and propoxur. Furthermore, P. papatasi of Surogia village had
      significantly higher insecticide detoxification enzyme activity than of those of
      Rahad Game Reserve. The sand fly population in Surogia displayed high AChE
      activity and only three specimens had elevated levels for EST and GST.
      CONCLUSIONS: The study provided evidence for malathion and propoxur resistance in
      the sand fly population of Surogia village, which probably resulted from anti
      malarial control activities carried out in the area during the past 50 years.

PMID- 22397727
TI  - Comparison of Cu(II)-promoted leaving group stabilization of the cleavage of a
      homologous set of phosphate mono-, di-, and triesters in water, methanol, and
      ethanol.
AB  - The cleavage of a set of phosphate mono-, di-, and triesters having a Cu(II)
      complexed 2-phenanthrolyl group at the ortho-position of a departing phenoxide
      was studied in water and ethanol. Experimentally observed pH/rate profiles,
      solvent deuterium kinetic isotope effects, and activation parameters are compared
      with those obtained in methanol. The pH/rate profile in each solvent exhibits an
      extended plateau due to solvent attack on forms designated as [Cu(II):1b/c](0)
      for the monoester, [Cu(II):2b](+), for the diester, and [Cu(II):3a](2+) for the
      triester. The solvent dkie values (k(H)/k(D)) for the three complexes are 0.91,
      0.95, and 0.83 for decomposition of [Cu(II):1b/c](0) in water (W), methanol (M),
      and ethanol (E), 1.22, 1.09, and 1.29 for [Cu(II):2b](+) in W, M, and E, and
      1.94, 2.2, and 1.96 for [Cu(II):3a](2+) in W, M, and E. Near unit, or slightly
      inverse values for the monoester are taken as evidence for little involvement of
      solvent in a highly dissociative TS for P-OAr cleavage, with slightly higher
      solvent dkie values for the diester signifying the onset of some solvent
      participation in assisting the nucleophilic displacement. The larger primary dkie
      for the triester gives evidence for a solvent-assisted delivery of ROH in the
      cleavage through a more associative mechanism. Activation parameters for each
      substrate in the solvents are compared, indicating that the transition from
      methanol to ethanol for each substrate involves a near cancellation of the
      DeltaDeltaH(?) and -TDeltaDeltaS(?) values (25  degrees C) so that the respective
      rates in both solvents are very similar. The transition from alcohol to water
      produces variable effects, with DeltaDeltaH(?) and -TDeltaDeltaS(?) values
      canceling for cleavage of the triester and being additive for the mono and
      diester, explaining their 100-500 rate reduction in passing from methanol to
      water. The rate enhancing effects of the Cu(II)-promoted leaving group assistance
      in all three solvents are substantial and estimated at 10(12)-10(15) for the
      monoester, 10(12)-10(14) for the diester, and 10(5) for the triester relative to
      their background reactions.

PMID- 22397728
TI  - Nanoscale measurement of the power spectral density of surface roughness: how to
      solve a difficult experimental challenge.
AB  - In this study, we show that the correct determination of surface morphology
      using scanning force microscopy (SFM) imaging and power spectral density (PSD)
      analysis of the surface roughness is an extremely demanding task that is easily
      affected by experimental parameters such as scan speed and feedback parameters.
      We present examples were the measured topography data is significantly influenced
      by the feedback response of the SFM system and the PSD curves calculated from
      this experimental data do not correspond to that of the true topography. Instead,
      either features are "lost" due to low pass filtering or features are "created"
      due to oscillation of the feedback loop. In order to overcome these serious
      problems we show that the interaction signal (error signal) can be used not only
      to quantitatively control but also to significantly improve the quality of the
      topography raw data used for the PSD analysis. In particular, the calibrated
      error signal image can be used in combination with the topography image in order
      to obtain a correct representation of surface morphology ("true" topographic
      image). From this "true" topographic image a faithful determination of the PSD of
      surface morphology is possible. The corresponding PSD curve is not affected by
      the fine-tuning of feedback parameters, and allows for much faster image
      acquisition speeds without loss of information in the PSD curve.

PMID- 22397730
TI  - Counterfactually mediated emotions: a developmental study of regret and relief in
      a probabilistic gambling task.
AB  - Regret and relief are related to counterfactual thinking and rely on comparison
      processes between what has been and what might have been. In this article, we
      study the development of regret and relief from late childhood to adulthood (11.2
      20.2 years), and we examine how these two emotions affect individuals'
      willingness to retrospectively reconsider their choice in a computerized monetary
      gambling task. We asked participants to choose between two "wheels of fortune"
      that differed in the amount of gain and loss expected and the probability of
      winning. We manipulated the outcome of the wheel of fortune that was not selected
      by participants to induce regret or relief. For each trial, participants rated
      how they felt about the outcome and their willingness to modify their choice.
      Participants' ratings suggest that regret and relief are stronger in adults than
      in children and adolescents. Regret affects participants' willingness to modify
      their initial choice, but this desire is stronger for adults than for children.
      In children, the experience of regret seems to be dissociated from the
      willingness to reconsider a choice. This study provides the first evidence that
      the ability to experience counterfactually mediated emotions, such as regret and
      relief, and the ability to take them into consideration continue to develop
      during late childhood and adolescence.

PMID- 22397729
TI  - Staging cancer of the uterus: a national audit of MRI accuracy.
AB  - AIM: To report the results of a nationwide audit of the accuracy of magnetic
      resonance imaging (MRI) staging in uterine body cancer when staging myometrial
      invasion, cervical extension, and lymph node spread. MATERIALS AND METHODS: All
      UK radiology departments were invited to participate using a web-based tool for
      submitting anonymized data for a 12 month period. MRI staging was compared with
      histopathological staging using target accuracies of 85, 86, and 70%
      respectively. RESULTS: Of the departments performing MRI staging of endometrial
      cancer, 37/87 departments contributed. Targets for MRI staging were achieved for
      two of the three standards nationally with diagnostic accuracy for depth of
      myometrial invasion, 82%; for cervical extension, 90%; and for pelvic nodal
      involvement, 94%; the latter two being well above the targets. However, only
      13/37 (35%) of individual centres met the target for assessing depth of
      myometrial invasion, 31/36 (86%) for cervical extension and 31/34 (91%) for
      pelvic nodal involvement. Statistical analysis demonstrated no significant
      difference for the use of intravenous contrast medium, but did show some evidence
      of increasing accuracy in assessment of depth of myometrial invasion with
      increasing caseload. CONCLUSION: Overall performance in the UK was good, with
      only the target for assessment of depth of myometrial invasion not being met.
      Inter-departmental variation was seen. One factor that may improve performance in
      assessment of myometrial invasion is a higher caseload. No other clear factor to
      improve performance were identified.

PMID- 22397731
TI  - Electrochemotherapy: Progress and Prospects.
AB  - Treatment of recurrent or unresectable cutaneous and subcutaneaous tumors
      continues to be a major therapeutic challenge. Electrochemotherapy (ECT) is a
      palliative treatment of cutaneous and subcutaneous tumor nodules for which
      standard treatments (e.g. radiotherapy, chemotherapy, and surgery) have failed or
      proved to be insufficient. ECT combines the electropulsation of tumor cells (by
      local application of electric pulses) and the administration of antineoplastic
      drugs such as cisplatin or bleomycin (either intravenous or intratumoral). The
      permeability of the cancer cells to these poorly permeant anti-tumor drugs is
      transiently increased up to a hundred-fold. ECT is thus an efficient loco
      regional therapy for palliative treatment of unresectable recurrent tumor nodules
      with overall objective response rates of approximatively 80-90% and has
      satisfactory cosmetic results. The next challenge for ECT is the treatment of
      deep-seated tumors and metastases. The joint therapy of ECT and electrotransfer
      of immune-stimulating genes or electro-photodynamic therapy could be a promising
      strategy for cancer eradication.

PMID- 22397732
TI  - Radiovirotherapy: principles and prospects in oncology.
AB  - Radiovirotherapy is defined as the use of viruses to deliver radioisotopic
      treatment into infected cells. Oncolytic viruses are able to selectively target
      and kill cancer cells. The combination of oncolytic viruses and radiation
      therapies can have synergistic antitumour properties. Viruses may act as
      radiosensitizers, and radiations can increase viral oncolytic properties. The
      combination of oncolytic viruses with a virally-directed radioisotope therapy is
      an innovative method to combine viruses and radiation therapy, selectively within
      the tumour cells. The sodium/iodide symporter (NIS) is the main transgene that
      has been studied for this approach. NIS can mediate the uptake of isotopes of
      iodine and technetium 99m for in vivo gene expression imaging and therapy. This
      review highlights the principles of radiovirotherapy, and its recent progress.
      Better understanding of the regulation of NIS opens up pathways by which to
      potentiate the functional expression of NIS. In terms of the therapeutic isotope,
      Iodine-131 has been most frequently studied but other isotopes (astatine- 211,
      rhenium-188) are of growing interest. Oncolytic viruses are able to infect
      selectively and replicate in cancer cells and promising early phase clinical
      trials have been recently published. Their development allows a better
      selectivity of viral infection and adds a virus-specific cytotoxicity to the
      therapeutic approach. Active research into strategies such as immunosuppressive
      treatment and cell-based carrier systems is seeking to circumvent the host
      antiviral immune response and, thus, increase the potential for systemic
      delivery. Finally, other anticancer therapies such as chemotherapy and external
      beam radiotherapy may have a synergistic effect with radiovirotherapy and such
      combinatorial approaches offering the prospect of accelerated translation into
      clinical studies.

PMID- 22397733
TI  - Beyond price: individuals' accounts of deciding to pay for private healthcare
      treatment in the UK.
AB  - BACKGROUND: Delivering appropriate and affordable healthcare is a concern across
      the globe. As countries grapple with the issue of delivering healthcare with
      finite resources and populations continue to age, more health-related care
      services or treatments may become an optional 'extra' to be purchased privately.
      It is timely to consider how, and to what extent, the individual can act as both
      a 'patient' and a 'consumer'. In the UK the majority of healthcare treatments are
      free at the point of delivery. However, increasingly some healthcare treatments
      are being made available via the private healthcare market. Drawing from insights
      from healthcare policy and social sciences, this paper uses the exemplar of
      private dental implant treatment provision in the UK to examine what factors
      people considered when deciding whether or not to pay for a costly healthcare
      treatment for a non-fatal condition. METHODS: Qualitative interviews with people
      (n = 27) who considered paying for dental implants treatments in the UK. Data
      collection and analysis processes followed the principles of the constant
      comparative methods, and thematic analysis was facilitated through the use of
      NVivo qualitative data software. RESULTS: Decisions to pay for private healthcare
      treatments are not simply determined by price. Decisions are mediated by: the
      perceived 'status' of the healthcare treatment as either functional or aesthetic;
      how the individual determines and values their 'need' for the treatment; and, the
      impact the expenditure may have on themselves and others. Choosing a private
      healthcare provider is sometimes determined simply by personal rapport or extant
      clinical relationship, or based on the recommendation of others. CONCLUSIONS: As
      private healthcare markets expand to provide more 'non-essential' services,
      patients need to develop new skills and to be supported in their new role as
      consumers.

PMID- 22397734
TI  - Affective forecasting and self-rated symptoms of depression, anxiety, and
      hypomania: evidence for a dysphoric forecasting bias.
AB  - Emerging research has examined individual differences in affective forecasting;
      however, we are aware of no published study to date linking psychopathology
      symptoms to affective forecasting problems. Pitting cognitive theory against
      depressive realism theory, we examined whether dysphoria was associated with
      negatively biased affective forecasts or greater accuracy. Participants (n=325)
      supplied predicted and actual emotional reactions for three days surrounding an
      emotionally evocative relational event, Valentine's Day. Predictions were made a
      month prior to the holiday. Consistent with cognitive theory, we found evidence
      for a dysphoric forecasting bias-the tendency of individuals in dysphoric states
      to overpredict negative emotional reactions to future events. The dysphoric
      forecasting bias was robust across ratings of positive and negative affect,
      forecasts for pleasant and unpleasant scenarios, continuous and categorical
      operationalisations of dysphoria, and three time points of observation. Similar
      biases were not observed in analyses examining the independent effects of anxiety
      and hypomania. Findings provide empirical evidence for the long-assumed influence
      of depressive symptoms on future expectations. The present investigation has
      implications for affective forecasting studies examining information-processing
      constructs, decision making, and broader domains of psychopathology.

PMID- 22397735
TI  - Synthesis of fused dihydropyrano(furano)pyridines via [4 + 2]-cycloaddition of 5
      alkenoxy substituted oxazoles.
AB  - A three-step procedure to access fused pyridines has been developed utilizing
      inexpensive amino acids and alkenols to form the key oxazole precursors. Yields
      are good to excellent and provide a rapid and inexpensive route to a range of
      pharmacologically and biologically valuable fused pyridines with difficult to
      access substitution patterns.

PMID- 22397736
TI  - A theoretical reappraisal of polylysine in the investigation of secondary
      structure sensitivity of infrared spectra.
AB  - Infrared spectroscopy has long provided a means to estimate the secondary
      structure of proteins and peptides. In particular, the vibrational spectra of the
      amide I' band have been widely used for this purpose as the frequency positions
      of the amide I' bands are related to the presence of specific secondary
      structures. Here, we calculate the amide I' IR spectra of polylysine in aqueous
      solution in its three secondary structure states, i.e., alpha-helix, beta-sheet,
      and random coil, by means of a mixed quantum mechanics/molecular dynamics (QM/MD)
      theoretical-computational methodology based on the perturbed matrix method (PMM).
      The computed spectra show a good agreement with the experimental ones. Although
      our calculations confirm the importance of the excitonic coupling in reproducing
      important spectral features (e.g., the width of the absorption band), the
      frequency shift due to secondary-structure changes is also well reproduced
      without the inclusion of the excitonic coupling, pointing to a role played by the
      local environment. Concerning the beta-conformation spectrum, which is
      characterized by a double-peak amide I' band due to excitonic coupling, our
      results indicate that it does not correspond to a generic antiparallel beta-sheet
      (e.g., of the typical size present in native proteins) but is rather
      representative of extended beta-structures, which are common in beta-aggregates.
      Moreover, we also show that the solvent has a crucial role in the shape
      determination of the beta-conformation amide I' band and in particular in the
      disappearance of the high-frequency secondary peak in the case of small sheets
      (e.g., 6-stranded).

PMID- 22397737
TI  - Structure and orientation of the gH625-644 membrane interacting region of herpes
      simplex virus type 1 in a membrane mimetic system.
AB  - Glycoprotein H (gH) of the herpes simplex virus type 1 is involved in the complex
      mechanism of membrane fusion of the viral envelope with host cells. The virus
      requires four glycoproteins (gB, gD, gH, gL) to execute fusion and the role
      played by gH remains mysterious. Mutational studies have revealed several regions
      of gH ectodomain required for fusion and identified the segment from amino acid
      625 to 644 as the most fusogenic region. Here, we studied the behavior in a
      membrane-mimicking DPC micellar environment of a peptide encompassing this region
      (gH625-644) and determined its NMR solution structure and its orientation within
      the micelles.

PMID- 22397738
TI  - Grooved nanowires from self-assembling hairpin molecules for solar cells.
AB  - One of the challenges facing bulk heterojunction organic solar cells is obtaining
      organized films during the phase separation of intimately mixed donor and
      acceptor components. We report here on the use of hairpin-shaped sexithiophene
      molecules to generate by self-assembly grooved nanowires as the donor component
      in bulk heterojunction solar cells. Photovoltaic devices were fabricated via spin
      casting to produce by solvent evaporation a percolating network of self-assembled
      nanowires and fullerene acceptors. Thermal annealing was found to increase power
      conversion efficiencies by promoting domain growth while still maintaining this
      percolating network of nanostructures. The benefits of self-assembly and grooved
      nanowires were examined by building devices from a soluble sexithiophene
      derivative that does not form one-dimensional structures. In these systems,
      excessive phase separation caused by thermal annealing leads to the formation of
      defects and lower device efficiencies. We propose that the unique hairpin shape
      of the self-assembling molecules allows the nanowires as they form to interact
      well with the fullerenes in receptor-ligand type configurations at the
      heterojunction of the two domains, thus enhancing device efficiencies by 23%.

PMID- 22397739
TI  - Use of the  13-valent pneumococcal conjugate vaccine  in infants and young
      children.
AB  - INTRODUCTION: The inclusion of the heptavalent pneumococcal conjugate vaccine
      (PCV7) in the immunization schedule of infants and young children has greatly
      reduced the incidence of invasive and non-invasive diseases due to Streptococcus
      pneumoniae. However, as PCV7 has some limitations, new vaccines containing more
      pneumococcal serotypes have been developed. Only two of these have so far reached
      the market: a 10-valent preparation containing the PCV7 serotypes plus serotypes
      1, 5 and 7F (PCV10), and a 13-valent vaccine containing the PCV7 serotypes plus
      serotypes 1, 3, 5, 6A, 7F and 19A (PCV13). AREAS COVERED: The main aim of this
      review is to discuss the reasons that have led to the formulation of PCV13, its
      immunogenicity, safety and tolerability and the recommendations concerning its
      use in children. EXPERT OPINION: There is no doubt that a pneumococcal conjugate
      vaccine with the composition of PCV13 has significantly increased the possibility
      of preventing pneumococcal disease. Its immunogenicity, safety and tolerability
      seem to be optimal, as does its cost-effectiveness. However, despite these
      favorable premises, it cannot be considered the final preparation for the
      prevention of pneumococcal disease, and it is likely that a new vaccine capable
      of covering all pneumococcal serotypes will be needed in the future.

PMID- 22397740
TI  - Circular DNA genomics (circomics) exemplified for geminiviruses in bean crops and
      weeds of northeastern Brazil.
AB  - Circomics was coined to describe the combination of rolling circle amplification
      (RCA), restriction fragment length polymorphism (RFLP) and pyro-sequencing to
      investigate the genome structures of small circular DNAs. A batch procedure is
      described using 61 plant samples from Asia, South America and Central America
      which revealed 83 contig sequences of geminiviral DNA components and 4 contig
      sequences of DNA satellites. The usefulness of this approach is validated for the
      Brazilian begomoviruses, and the sequence fidelity is determined by comparing the
      results with those of conventional cloning and sequencing of Bolivian
      begomoviruses reported recently. Therefore, circomics has been proven to be a
      major step forward to economize costs and labor and to characterize reliably
      geminiviral genomes in their population structure of the quasispecies.

PMID- 22397741
TI  - Agreement and correlation between the self-report leeds assessment of neuropathic
      symptoms and signs and Douleur Neuropathique 4 Questions neuropathic pain
      screening tools in subjects with low back-related leg pain.
AB  - OBJECTIVE: The self-report Leeds Assessment of Neuropathic Symptoms and Signs (S
      LANSS) and Douleur Neuropathique 4 Questions (DN4) neuropathic pain screening
      tools have been shown to be reliable, valid, and able to differentiate
      neuropathic pain from inflammatory or mixed pain syndromes. However, no studies
      have compared these tools to determine whether their outcomes are similar. This
      study evaluated agreement and correlation between the S-LANSS and DN4 in the
      identification of neuropathic pain in subjects with low back-related leg pain.
      METHODS: This observational study compared S-LANSS and DN4 scores in 45 patients
      with low back-related leg pain. The S-LANSS and DN4 cutoff scores of 12 and 4,
      respectively, were used to classify subjects as positive or negative for the
      presence of neuropathic pain for each screening tool. The kappa statistic was
      used to determine whether there was agreement in classification of neuropathic
      pain between the 2 screening tools. Pearson correlation coefficient was used to
      determine correlation between scores of the 2 screening tools. RESULTS:
      Neuropathic pain was identified in 15 subjects (33%) using the S-LANSS and in 19
      subjects (42%) using the DN4. Agreement on neuropathic pain classification was
      fair, with a kappa value of 0.34. There was moderate to good correlation (r =
      0.62; P < .001) between scores obtained from the 2 tools. CONCLUSIONS: The
      finding of fair agreement suggests that despite the moderate to good correlation
      between scores, the cutoff points for the classification of neuropathic pain of
      the 2 tools may not be congruent.

PMID- 22397742
TI  - The use of synthetic mesh in vaginal prolapse surgery: a survey of Dutch
      urogynaecologists.
AB  - OBJECTIVE: To evaluate the use of mesh in vaginal prolapse surgery amongst
      members of the Dutch Urogynaecologic Society. STUDY DESIGN: A questionnaire
      evaluating the use of mesh vs. native tissue repair in vaginal prolapse surgery
      was sent out by email to all members. Some specific questions on standard
      measures of infection prevention were included. RESULTS: One hundred and thirty
      three completed questionnaires were received. The response rate was 65%. Seventy
      one percent of respondents stated that they apply use synthetic meshes in their
      patients. The mean percentage of mesh use in overall vaginal pelvic organ
      prolapse surgery was 14%. Most responders use mesh in recurrent surgery only.
      Prolift is the most commonly used brand. All women received prophylactic
      antibiotics. Although only half of the respondents changed gloves. CONCLUSIONS:
      Meshes are commonly used in the Netherlands. The major indication is repair of a
      recurrent prolapse.

PMID- 22397743
TI  - Are plasma levels of visfatin and retinol-binding protein 4 (RBP4) associated
      with body mass, metabolic and hormonal disturbances in women with polycystic
      ovary syndrome?
AB  - OBJECTIVE: To analyze potential interactions of visfatin and retinol-binding
      protein 4 (RBP4) levels with body mass, metabolic, and hormonal status in normal
      weight and obese women with PCOS. STUDY DESIGN: Body composition was determined
      by bioimpedance in 83 women (44 obese) diagnosed with PCOS and in 67 women (36
      obese) without PCOS. In addition, serum glucose, lipids, androgens, FSH, LH,
      SHBG, insulin, visfatin, and RBP4 were measured in a fasting state and the free
      androgen index (FAI) was calculated, as was insulin resistance using the HOMA-IR
      assessment. RESULTS: Plasma RBP4 levels were significantly higher in women of
      normal weight compared to obese subjects when both were diagnosed with PCOS (14.1
      +/- 4.6 vs.10.9 +/- 4.5 ng/mL, p<0.001); while in non-PCOS subjects the opposite
      was found (10.8 +/- 4.5 vs. 18.4 +/- 11.6 ng/mL, p<0.01; respectively). Plasma
      visfatin levels were similar in PCOS and non-PCOS subjects. In non-PCOS subjects,
      positive correlations between RBP4 level and anthropometric parameters were
      observed. In PCOS, RBP4 levels inversely correlated with serum insulin levels and
      HOMA-IR values. No correlation was found between plasma visfatin levels and
      anthropometric parameters in all study groups. Similarly, no correlation was
      found in PCOS and non-PCOS subgroups. Additionally, there was an inverse
      correlation between RBP4 and LH concentrations and LH/FSH ratio in all study
      subjects. CONCLUSIONS: Plasma visfatin level is not a useful biomarker of insulin
      resistance and hyperandrogenism. RBP4 level reflects visceral body fat content in
      non-PCOS women. Decreasing RBP4 release along with increasing insulin resistance
      and hormonal disturbances may be a compensatory mechanism preventing
      deterioration in obese PCOS.

PMID- 22397744
TI  - Peritoneal tuberculosis mimicking ovarian cancer.
AB  - OBJECTIVE: To evaluate the characteristics of 20 patients diagnosed as
      tuberculous peritonitis (TBP) mimicking ovarian cancer during a 10-year period at
      a single center. STUDY DESIGN: Among 612 operations for ovarian malignancy we
      retrospectively reviewed the surgical and pathological reports of 20 patients
      suspected preoperatively as having ovarian malignancy but whose pathological
      results revealed TBP, between 2000 and 2011 in a university clinic. Demographic
      characteristics, physical and pelvic examination, laboratory investigations and
      radiological imaging of the patients were evaluated retrospectively. RESULTS:
      Diagnostic laparotomy, laparoscopy and ultrasound guided tru-cut biopsy were
      performed in 11, 2 and 7 of the 20 patients, respectively. The mean age of the
      patients was 37.5 +/- 17.3 years (range 16-70 years). The most common symptoms
      were abdominal pain (n=14%, 70%) and abdominal distension (n=13%, 65%). Serum CA
      125 was elevated in 16 (80%) cases and the average CA 125 level was 289 +/- 186.2
      IU/ml. During ultrasonographic imaging and CT scans, ascites and a pelvic mass
      were detected in 19 (85%) and 12 (60%) patients respectively. TBP was suspected
      in 7 (35%) patients and ultrasound guided tru-cut biopsy was preferred as a first
      line approach. Surgery was performed in 11 patients (55%) and during exploration
      widespread miliary nodules (n=9%, 81%), widespread adhesion (n=5%, 45%), adnexal
      mass (n=8%, 72%) and caseous necrotic substance (n=4%, 36%) were observed.
      Patients underwent unilateral (n=3% 27%) or bilateral (n=4%, 36%) salpingo
      oophorectomy in seven (63%) cases. CONCLUSION: Since ovarian cancer is a serious
      condition and preoperative diagnosis of TBP is difficult, laparotomy is usually
      mandatory to distinguish these two entities. Ultrasound guided tru-cut biopsy is
      useful in selected patients and frozen section analysis avoids hazardous radical
      surgery at operation.

PMID- 22397745
TI  - Post-mortem examination after stillbirth: views of UK-based practitioners.
AB  - OBJECTIVES: Worldwide, around four million stillbirths occur annually. The UK was
      recently ranked as 33rd out of 35 developed nations for stillbirth rates. The
      reasons for many stillbirths remain unexplained. Post-mortem examination (PME)
      can provide information for grieving families, and for future pregnancies. Rates
      of consent for PME are decreasing in the UK. The views of professionals may
      influence their approach to bereaved families, and, therefore, rates of consent.
      Arguably, obtaining qualitative insights into emotive areas such as PME from
      large numbers of practitioners is increasingly possible as electronic surveys
      become more sophisticated. Therefore we aimed to describe, using electronic
      media, the views of UK obstetricians, midwives and perinatal pathologists about
      PME for stillbirth. STUDY DESIGN: 10,000 UK midwives, 1136 UK obstetricians and
      all 40 UK perinatal pathologists received a link to an Internet survey via their
      professional organizations. A box was included for free-text responses. Iterative
      thematic analysis generated five themes and a 'line of argument' synthesis.
      RESULTS: 683 midwives, 98 obstetricians, and 11 perinatal pathologists provided
      open comments, generating five themes and the following line of argument: both
      professional views and family decision-making about postmortem after stillbirth
      are affected by the education and training of staff, local resources, and the
      quality of information available. All of these structural issues are interpreted
      by individual staff, women and families through personal beliefs and emotions,
      and professional and social discourses. CONCLUSIONS: Internet-based surveys can
      generate valuable qualitative data. Effective decision-making for post-mortem
      after stillbirth may be improved by the introduction of user-friendly information
      and consent procedures, and staff training that takes account of existing
      innovations, and of the emotions and prior experiences of both staff and parents.

PMID- 22397746
TI  - The surgical management of complications of vulval lichen sclerosus.
AB  - OBJECTIVE: To review the surgical procedures used to treat the complications of
      vulval lichen sclerosus at a single tertiary referral institution in north-east
      Scotland over a ten year period. STUDY DESIGN: A retrospective case note review
      of women who had surgery for ano-genital lichen sclerosus at Aberdeen Royal
      Infirmary between January 1999 and December 2009. RESULTS: The total number of
      women was 25 and the two most common procedures were Fenton's procedure (median
      perineotomy) and laser division of adhesions. Initial surgery resulted in an
      improvement of symptoms for 80% of women. CONCLUSIONS: When surgery for vulval
      lichen sclerosus is reserved for highly selected cases where there are
      complications secondary to adhesions, the proportion of women benefiting is high.

PMID- 22397747
TI  - Ischemic stroke after ovulation induction in a patient with cardiac and
      thrombophilic abnormalities.

PMID- 22397748
TI  - Repeat transvaginal ultrasound-guided ovarian interstitial laser treatment
      improved the anovulatory status in women with polycystic ovarian syndrome.
AB  - OBJECTIVE: To assess the effectiveness of repeated transvaginal ultrasound-guided
      ovarian interstitial laser treatment in the management of anovulatory patients
      with polycystic ovary syndrome (PCOS). STUDY DESIGN: A retrospective study was
      performed in our department on 27 anovulatory PCOS women who failed to respond to
      the first ultrasound-guided transvaginal ovarian interstitial laser treatment.
      Each woman received a repeat procedure and postoperative rates of ovulation and
      pregnancy were monitored. RESULTS: Of 27 patients, 18 (66.67%) ovulated
      spontaneously following the repeated ultrasound-guided transvaginal ovarian
      interstitial laser treatment Ten women became pregnant within six postoperative
      months and a cumulative pregnancy rate of 37.04% was achieved. There were no
      significant operative complications. CONCLUSION: Repeated ultrasound-guided
      transvaginal ovarian interstitial laser treatment is an effective and safe
      management in anovulatory PCOS patients who fail to respond or have a transient
      response to the first transvaginal ovarian interstitial laser treatment.

PMID- 22397749
TI  - How deviations from STAN guidelines contribute to operative delivery for
      suspected fetal distress.
AB  - OBJECTIVE: To evaluate how deviations from STAN guidelines contribute to
      operative delivery for suspected fetal distress in a high-risk population. STUDY
      DESIGN: This retrospective cohort study was conducted in a tertiary referral
      center with about 3000 deliveries a year. During the study period, STAN usage
      rate was 15.2%. All consecutive patients monitored with STAN who had an operative
      delivery for suspected fetal distress were included in the index group. Patients
      who delivered spontaneously or had an operative delivery for any reason other
      than suspected fetal distress were included as controls. Case review was
      performed by three referent obstetricians for STAN technology blinded to neonatal
      outcomes. Main outcome was agreement between decision made and decision
      recommended by STAN clinical guidelines. Secondary outcomes were reasons
      explaining guideline deviation and ST event to birth interval in cases with a
      significant ST event. RESULTS: Eighty-three patients were included in each group.
      Decision made was consistent with STAN clinical guidelines in 124 patients
      (74.7%): 50 patients (60.2%) in the index group and 74 patients (89.2%) in the
      control group (p<0.05). Among these patients, no fetal metabolic acidosis was
      reported. Decision made was not consistent with STAN labor management guidelines
      in 42 patients (24.3%): 33 patients (39.8%) in the index group and 9 (10.8%) in
      the control group (p<0.05). Including ST event to birth interval, interventions
      were outwith STAN clinical guidelines in 51.4% of patients with suspected fetal
      distress. CTG misclassification was involved in over 75% of cases. CONCLUSION:
      STAN guideline deviations contribute to an increased operative delivery rate in
      patients with suspected fetal distress and normal neonatal outcomes. Guideline
      deviations are more frequent in patients with suspected fetal distress than in
      controls. CTG misclassification was the leading cause of guideline deviation.
      STAN guideline deviations may contribute to alter STAN specificity.

PMID- 22397750
TI  - [The elderly and advertising: a history of misunderstanding].

PMID- 22397752
TI  - Assessment of cavopulmonary connections by advanced imaging: value of flat
      detector computed tomography.
AB  - OBJECTIVES: To investigate the impact of flat-detector computed tomography on the
      clinical assessment of patients with cavopulmonary connections, and to evaluate
      the obtained diagnostic accuracy and supplementary information, as well as the
      value of overlaid three-dimensional reconstructions on fluoroscopic images during
      catheter-based interventions. METHODS: We analysed 31 consecutive patients
      retrospectively in whom flat-detector computed tomography was used to visualise
      the cavopulmonary connection. We investigated patients with cavopulmonary
      connections either early post-operatively (first group), before converting to a
      total cavopulmonary connection (second group), and patients with failing total
      cavopulmonary connection (third group). Flat-detector computed tomography based
      on a single rotational angiography was used to create a three-dimensional
      vascular model. The clinical value of flat-detector computed tomography was
      evaluated using standard categories of diagnostic utility. Used contrast volume
      and radiation exposure were quantified. RESULTS: Within 18 months, flat-detector
      computed tomography was performed in 31 cases with cavopulmonary connections. The
      median age was 1.9 years (range 0.3-43 years). In the first group, we found
      anomalies in 4 out of 8 cases, which led to therapeutic or prophylactic
      procedures; in the second and third groups, we performed interventions in 14 out
      of 23 cases. The overall clinical value was always rated superior to conventional
      biplane angiography. The median dose area product was 91.8 microgray square
      metres (range 33.0-679.3 microgray square metres). The required contrast medium
      was 2.08 millilitres per kilogram (range 0.66-4.7 millilitres per kilogram).
      CONCLUSION: Flat-detector computed tomography improves the diagnostic accuracy in
      cavopulmonary connections and provides additional diagnostic information, which
      may lead to therapeutic or prophylactic procedures. Overlaid three-dimensional
      images on fluoroscopy facilitate and provide security for interventions.

PMID- 22397751
TI  - Protein pharmacophore selection using hydration-site analysis.
AB  - Virtual screening using pharmacophore models is an efficient method to identify
      potential lead compounds for target proteins. Pharmacophore models based on
      protein structures are advantageous because a priori knowledge of active ligands
      is not required and the models are not biased by the chemical space of previously
      identified actives. However, in order to capture most potential interactions
      between all potentially binding ligands and the protein, the size of the
      pharmacophore model, i.e. number of pharmacophore elements, is typically quite
      large and therefore reduces the efficiency of pharmacophore based screening. We
      have developed a new method to select important pharmacophore elements using
      hydration-site information. The basic premise is that ligand functional groups
      that replace water molecules in the apo protein contribute strongly to the
      overall binding affinity of the ligand, due to the additional free energy gained
      from releasing the water molecule into the bulk solvent. We computed the free
      energy of water released from the binding site for each hydration site using
      thermodynamic analysis of molecular dynamics (MD) simulations. Pharmacophores
      which are colocalized with hydration sites with estimated favorable contributions
      to the free energy of binding are selected to generate a reduced pharmacophore
      model. We constructed reduced pharmacophore models for three protein systems and
      demonstrated good enrichment quality combined with high efficiency. The reduction
      in pharmacophore model size reduces the required screening time by a factor of
      200-500 compared to using all protein pharmacophore elements. We also describe a
      training process using a small set of known actives to reliably select the
      optimal set of criteria for pharmacophore selection for each protein system.

PMID- 22397753
TI  - Electron spin density distribution in the special pair triplet of Rhodobacter
      sphaeroides R26 revealed by magnetic field dependence of the solid-state photo
      CIDNP effect.
AB  - Photo-CIDNP (photochemically induced dynamic nuclear polarization) can be
      observed in frozen and quinone-blocked photosynthetic reaction centers (RCs) as
      modification of magic-angle spinning (MAS) NMR signal intensity under
      illumination. Studying the carotenoidless mutant strain R26 of Rhodobacter
      sphaeroides, we demonstrate by experiment and theory that contributions to the
      nuclear spin polarization from the three-spin mixing and differential decay
      mechanism can be separated from polarization generated by the radical pair
      mechanism, which is partially maintained due to differential relaxation (DR) in
      the singlet and triplet branch. At a magnetic field of 1.4 T, the latter
      contribution leads to dramatic signal enhancement of about 80,000 and dominates
      over the two other mechanisms. The DR mechanism encodes information on the spin
      density distribution in the donor triplet state. Relative peak intensities in the
      photo-CIDNP spectra provide a critical test for triplet spin densities computed
      for different model chemistries and conformations. The unpaired electrons are
      distributed almost evenly over the two moieties of the special pair of
      bacteriochlorophylls, with only slight excess in the L branch.

PMID- 22397754
TI  - The nitridation of ZnO nanowires.
AB  - ZnO nanowires (NWs) with diameters of 50 to 250 nm and lengths of several
      micrometres have been grown by reactive vapour transport via the reaction of Zn
      with oxygen on 1 nm Au/Si(001) at 550 degrees C under an inert flow of Ar. These
      exhibited clear peaks in the X-ray diffraction corresponding to the hexagonal
      wurtzite crystal structure of ZnO and a photoluminescence spectrum with a peak at
      3.3 eV corresponding to band edge emission close to 3.2 eV determined from the
      abrupt onset in the absorption-transmission through ZnO NWs grown on 0.5 nm
      Au/quartz. We find that the post growth nitridation of ZnO NWs under a steady
      flow of NH3 at temperatures <=600 degrees C promotes the formation of a ZnO/Zn3N2
      core-shell structure as suggested by the suppression of the peaks related to ZnO
      and the emergence of new ones corresponding to the cubic crystal structure of
      Zn3N2 while maintaining their integrity. Higher temperatures lead to the complete
      elimination of the ZnO NWs. We discuss the effect of nitridation time, flow of
      NH3, ramp rate and hydrogen on the conversion and propose a mechanism for the
      nitridation.

PMID- 22397755
TI  - Sonic hedgehog signaling regulates Bcr-Abl expression in human chronic myeloid
      leukemia cells.
AB  - PURPOSE: Bcr-Abl fusion protein activates tyrosine kinase, resulting in the
      proliferation of leukemia cells, especially chronic myeloid leukemia (CML) cells.
      Imatinib (IM) effectively targets Bcr-Abl tyrosine kinase, but development of
      resistance to IM occurs with varying frequency. METHODS: Elucidation of the
      common regulatory pathway upstream of Bcr-Abl in IM-sensitive and IM-resistant
      CML cells is important for developing novel therapeutics against CML. RESULTS:
      This study demonstrated that IM preferentially inhibited the viability and Bcr
      Abl expression in IM-sensitive K562 (K562) cells, but not in Bcr-Abl
      overexpressing IM-resistant K562 (K562R) cells. Both K562 and K562R cells
      expressed Shh preproprotein, cleaved Shh C-terminal and N-terminal peptides, as
      well as mRNA level of major Shh signaling molecules, including sonic hedgehog
      (Shh), patched (PTCH), smoothened (Smo) and Gli-1. Moreover, Gli-1 translocation
      into nucleus was evident in these two cell lines, suggesting that both K562 and
      K562R cells possess activated and major components of the Shh signaling pathway.
      Silencing of Gli-1 by interference RNA was accompanied by inhibition of Bcr-Abl
      protein expression. Pharmacological suppression of Bcr-Abl expression was
      restored by the Smo agonist purmorpharmine. Treatment of Shh peptide in both K562
      and K562R cells not only increased Shh and Gli-1 expression, but also up
      regulated Bcr-Abl expression. Resveratrol, a known Bcr-Abl inhibitor, reduced Gli
      1 activation and inhibited the viability of CML cells. CONCLUSIONS: Shh signaling
      may regulate Bcr-Abl expression in human chronic myeloid leukemia cells. Novel
      compounds inhibiting both Shh signaling and Bcr-Abl expression, such as
      resveratrol, may have potential to be effective agents against CML independent of
      IM resistance.

PMID- 22397756
TI  - Preparation and antiprotozoal evaluation of promising beta-carboline alkaloids.
AB  - The synthesis of beta-carbolines and their in vitro antiplasmodial and
      antileishmanial activities were described herein. These molecules have also been
      studied concerning their in vitro cytotoxicity toward the human cell line THP1,
      in order to calculate their respective selectivity indexes (SI). Among the 20
      tested molecules, four exhibited significant antiplasmodial activity on the W2
      multi-resistant Plasmodium falciparum strain (0.7 < IC50 < 1.7 MUM), in
      comparison with two references drugs (chloroquine and doxycycline), and a low
      cytotoxicity. These beta-carbolines were also evaluated concerning their in vitro
      antileshmanial activity on Leishmania donovani promastigotes, permitting to
      identify an antileshmanial hit compound, displaying quite promising activity
      (IC50 = 6.1 MUM) in comparison with amphotericin B and pentamidine chosen as
      reference drugs. Finally, structure-activity relationships were discussed,
      pointing out that molecules presenting a para-substituted phenyl moiety at
      position 1 of the beta-carboline ring displayed the best biological profile.

PMID- 22397757
TI  - In vitro assessment of cytochrome P450 inhibition and induction potential of
      felotaxel (SHR110008).
AB  - The purpose of this study was to assess the potential inhibitory and inductive
      effects of felotaxel on cytochrome P450 isozymes in vitro. The inhibitory effects
      of felotaxel on various CYP isozymes were determined in human liver microsomes.
      In addition, the ability of felotaxel to induce CYP enzymes in cultured human
      hepatocytes was evaluated. Results showed that felotaxel did not inhibit CYP1A2-,
      CYP2C9-, CYP2C19-, CYP2E1-, CYP2D6-, CYP2B6-, CYP2C8-, and mediated activities in
      human liver microsomes up to a concentration of 100 MUM, while the inhibition
      (<30% inhibition) of CYP3A4 activities was observed at 100 MUM felotaxel. In
      vitro felotaxel did not induce CYP1A2, CYP2C19, or CYP3A4/5 activities in
      cultured human hepatocytes. In present study, felotaxel has been identified as a
      potent inhibitor of metabolic activity of CYP3A4. Therefore, clinically relevant
      pharmacokinetic drug-drug interactions are likely to occur between felotaxel and
      co-administered substrates of these CYP3A4 isozymes. These findings provided some
      useful information for safe and effective use of felotaxel in clinical practice.

PMID- 22397758
TI  - The effect of monosialotetrahexosylganglioside (GM1) in prevention of oxaliplatin
      induced neurotoxicity: a retrospective study.
AB  - Oxaliplatin is a key agent in the treatment of colorectal cancer. However,
      peripheral neuropathy markedly limits the use of oxaliplatin. This retrospective
      study was performed to assess the efficacy of monosialotetrahexosylganglioside
      (GM1) for preventing oxaliplatin induced neurotoxicity. Patients with colorectal
      cancer treated with oxaliplatin based chemotherapy (FOLFOX or XELOX) were
      retrospectively divided into two groups according to the use of GM1. The severity
      of neurotoxicity and efficacy of oxaliplatin were evaluated. A total of 278 cases
      were included, 114 in GM1 group and 164 in control group. A significantly lower
      incidence of grade 1-3 acute neurotoxicity (81% vs 92%, p=0.006), grade 2 acute
      neurotoxicity (26% vs 45%, p=0.002) was observed in GM1 group. Similarly,
      incidence of grade 1-3 (30% vs 48%, p=0.003) and grade 3 chronic neurotoxicity
      (4% vs 13%, p=0.021) was also lower in GM1 group. No difference was detected in
      objective response rate, progress free survival, and median overall survival
      between GM1 group and control group. The retrospective study demonstrated that
      GM1 significantly reduced the incidence of oxaliplatin induced neuropathy,
      especially severe neuropathy, without impairment of efficacy. Prospective trials
      of GM1 as neuroprotective of oxaliplatin treatment in colorectal cancer are
      warranted.

PMID- 22397760
TI  - Non-invasive skin biomarkers quantification of psoriasis and atopic dermatitis:
      cytokines, antioxidants and psoriatic skin auto-fluorescence.
AB  - BACKGROUND: Psoriasis and atopic dermatitis (AD) are challenging to treat due to
      the absence of suitable monitoring procedure and their recurrences. Alteration of
      skin hydrophilic biomarkers (SHB) and structural elements occur in both disorders
      and may possess a distinct profile for each clinical condition. OBJECTIVE: To
      quantify skin cytokines and antioxidants non-invasively in psoriatic and in AD
      patients and to evaluate skin auto-fluorescence in psoriatic patients. METHODS: A
      skin wash sampling technique was utilized to detect the expression of SHB on
      psoriatic and AD patients and healthy controls. Inflammatory cytokine (TNFalpha,
      IL-1alpha and IL-6) levels, total antioxidant scavenging capacity and uric acid
      content were estimated. Additionally, measurement of the fluorescent emission
      spectra of tryptophan moieties, collagen cross-links and elastin cross-links were
      performed on psoriatic patients and healthy controls. RESULTS: Our findings
      demonstrate significant alterations of the SHB levels among psoriasis, AD and
      healthy skin. Differences were also observed between lesional and non-lesional
      areas in patients with psoriasis and AD. Ultra-structural changes were found in
      psoriatic patients both in lesional and non-lesional areas. CONCLUSION: Employing
      non-invasive measurements of skin wash sampling and skin auto-fluorescence might
      serve as complementary analysis for improved diagnosis and treatment of psoriasis
      and AD. Furthermore, they may serve as an additional monitoring tool for various
      diseases, in which skin dysfunction is involved.

PMID- 22397759
TI  - Role of Sulindac and Celecoxib in the regulation of angiogenesis during the early
      neoplasm of colon: exploring PI3-K/PTEN/Akt pathway to the canonical Wnt/beta
      catenin signaling.
AB  - Angiogenesis refers to the generation of new blood vasculature from the nearby
      pre-existing one and is regulated by a balance between the pro- and anti
      angiogenic factors. During carcinogenesis, pro-angiogenic factors dominate and
      initialize the growth of new blood capillaries to provide nutrition, growth
      factors and overcome hypoxia inside the tumor microenvironment. In the present
      study, we have observed the role of Phosphatidylinositol-3-kinase (PI3
      K)/Phophatase and tensin homolog deleted on chromosome ten (PTEN)/Akt (Protein
      kinase B) pathway and canonical Wnt/beta-catenin downstream signaling in the
      regulation of various pro-angiogenic molecules including the vascular endocrine
      growth factor-A (VEGF-A), matix metalloproteinases (MMPs), inducible nitric oxide
      synthase (iNOS) and chemokines for the progression of experimental colorectal
      cancer with 1,2-dimethylhydrazine dihydrochloride (DMH) and anti-angiogenic
      effects of two non-steroidal anti-inflammatory drugs (NSAIDs) viz. Sulindac and
      Celecoxib. Morphological and histopathological studies were performed to analyze
      the tumorigenic modifications while flow cytometry for the relative
      quantification of apoptotic events. Transcriptional and translational
      modifications of biomolecules were analyzed via Reverse Transcriptase-and
      quantitative Real Time PCR, Western immoblotting and immunoflurescence,
      respectively. In vitro phosphorylation, gelatin zymography and nitric oxide (NO)
      assay were performed to observe the activation states of Akt, MMPs and iNOS
      enzyme, respectively. Dysregultion in Akt activation, and thereby, aberrant
      signaling of beta-catenin along with the production of NO could positively
      regulate tumor angiogenesis. NSAIDs can overcome these carcinogenic effects by
      controlling various key check points including higher PTEN and glycogen synthase
      kinase-3beta (GSK-3beta) expression and repressing Akt, MMPs and iNOS activation
      while inducing apoptosis among the cancer cells.

PMID- 22397761
TI  - Functionalization of single-walled carbon nanotubes enables efficient
      intracellular delivery of siRNA targeting MDM2 to inhibit breast cancer cells
      growth.
AB  - The delivery of DNA or RNA to cells represents the limiting step in the
      development of cancer gene therapy and RNA interference protocols. Single walled
      carbon nanotubes (SWNTs) are of interest as carriers of biologically active
      molecules because of their ability to cross cell membranes. In this study, we
      developed a novel strategy for chemical functionalization of SWNTs (f-SWCNTs)
      with DSPE-PEG-Amine to bind small interfering RNA (siRNA) by disulfide bonds
      applied to siRNA-mediated gene silencing in breast cancer cells. Results
      indicated the efficiency of f-SWNTs carrying siRNA reached 83.55%, and the new f
      SWNTs-siRNA-MDM2 complexes were successfully introduced into the breast carcinoma
      B-Cap-37 cells at a concentration of 100 nM in mediums, and caused proliferation
      inhibition of B-Cap-37 cells significantly. The proliferation inhibition ratio of
      B-Cap-37 cells was detected as 44.53% for 72 h, and the apoptosis ratio was
      measured as 30.45%. It was obvious that MDM2 can serve as a novel therapeutic
      target by an effective carrier system of DSPE-PEG-Amine-functionalized SWNTs,
      which would be very advanced and significant to therapy of breast cancer further.

PMID- 22397762
TI  - Progranulin expression in breast cancer with different intrinsic subtypes.
AB  - Progranulin is a newly discovered 88-kDa glycoprotein originally purified from
      the highly tumorigenic mouse teratoma-derived cell line PC. We found that high
      progranulin expression was associated with higher breast carcinoma angiogenesis,
      reflected by increased vascular endothelial growth factor expression and higher
      microvessel density. However, no immunohistochemical evidence currently exists to
      correlate progranulin expression with clinicopathological features in different
      intrinsic subtypes of breast carcinoma biopsies. The aim of this study was to
      investigate the progranulin expression profiles in the intrinsic subtypes of
      breast carcinomas and their relevance to histopathological and
      clinicopathological features. Tissue blocks containing 264 cases of breast
      carcinomas from 2006 to 2009 were classified as different intrinsic subtypes.
      Tissues of four intrinsic subtypes were immunostained for progranulin, vascular
      endothelial growth factor and CD105. Their relevance to histopathological and
      clinicopathological features was also analyzed. Twenty tissue samples from breast
      fibroadenomas were included in this study. Progranulin expression showed no
      significant differences in different intrinsic subtypes, although an increasing
      tendency could be found in the triple-negative breast cancer (TNBC) subgroup
      (chi(2)=5.00, df=3, p=0.17). However, differences were significant when
      pathologically node metastasis-positive (pN(+)) TNBC were excluded (chi(2)=17.84,
      df=3, p<0.01). Some clinicopathological parameters, including CK5/6 (chi(2)=0.08,
      df=3, p=0.78), E-cadherin (chi(2)=0.71, df=3, p=0.40) and P53 (chi(2)=0.05, df=3,
      p=0.83), displayed no correlation with activity of progranulin in pathologically
      node metastasis-negative (pN(-)) TNBC. It was noted that the EGFR expression
      level of the pN(-) TNBC subtype was significantly higher in cases with strong
      progranulin expression than in cases with weak progranulin expression
      (chi(2)=11.26, df=1, p<0.01). A significantly higher expression level of
      progranulin in pN(-) TNBC suggests that progranulin is a promising new target for
      pN(-) TNBC treatment. Strong expression of progranulin correlates with positive
      EGFR expression in the pN(-) TNBC subtype. The close relationship between EGFR
      and progranulin/VEGF/CD105 expression may partly play a role in high angiogenesis
      levels in the pN(-) TNBC subtype.

PMID- 22397763
TI  - Helminth communities from two urban rat populations in Kuala Lumpur, Malaysia.
AB  - BACKGROUND: The prevalence of parasitic infections among commensal animals such
      as black and brown rats in many tropical countries is high and in comparison with
      studies on rodents in temperate climates, little is known about the community
      structure of their parasites. Rodent borne parasites pose threats to human health
      since people living in close proximity to rodent populations can be exposed to
      infection. METHODS: The helminth community structures of two urban rat
      populations in Kuala Lumpur, Malaysia were investigated. The rats were from two
      contrasting sites in the city caught over a period of 21 months in 2000-2002.
      RESULTS: Eleven species of helminth parasites comprising seven nematodes
      (Heterakis spumosum, Mastophorus muris, Nippostrongylus brasiliensis, Syphacia
      muris, Pterygodermatites tani/whartoni, Gongylonema neoplasticum, Angiostrongylus
      malaysiensis), three cestodes (Hymenolepis (Rodentolepis) nana, H. diminuta and
      Taenia taeniaeformis) and one acanthocephalan (Moniliformis moniliformis) were
      recovered from 346 Rattus rattus and 104 R. norvegicus from two urban sites,
      Bangsar and Chow Kit, during 2000-2002. Rattus rattus harboured over 60% of all
      helminths compared with R. norvegicus, although both host species played a
      dominant role in the different sites with, for example R. norvegicus at Bangsar
      and R. rattus at Chow Kit accounting for most of the nematodes. Overall 80% of
      rats carried at least one species of helminth, with the highest prevalences being
      shown by H. diminuta (35%), H. spumosum (29.8%) and H. nana (28.4%).
      Nevertheless, there were marked differences in prevalence rates between sites and
      hosts. The influence of extrinsic (year, season and site) and intrinsic (species,
      sex and age) factors affecting infracommunity structure (abundance and prevalence
      of infection) and measures of component community structure were analyzed.
      CONCLUSIONS: Since at least two species of rat borne helminths in Kuala Lumpur
      have the potential to infect humans, and these showed high prevalences in the
      rats, the assessment and regular monitoring of infections carried by wild rodents
      have important roles to play in public health.

PMID- 22397764
TI  - ALK translocation and crizotinib in non-small cell lung cancer: an evolving
      paradigm in oncology drug development.
AB  - Advances in our understanding of tumour biology have encouraged reassessment of
      tumour classification by the site of origin in favour of molecular
      characteristics and/or oncogenic drivers amenable to treatment. The
      identification of EML4-anaplastic lymphoma kinase (ALK) as an oncogenic driver in
      non-small cell lung cancer (NSCLC) early in the clinical development of
      crizotinib and the observation of promising clinical responses in patients with
      NSCLC harbouring ALK translocations accelerated its clinical development in ALK
      positive NSCLC. Phase I and II trials of crizotinib in patients with ALK-positive
      advanced NSCLC reported notably high response rates that tended to be rapid and
      of prolonged duration. Crizotinib was well tolerated; treatment-related adverse
      events were typically gastrointestinal (grade 1/2) and visual disorders (almost
      exclusively grade 1). Crizotinib provided NSCLC symptom relief and maintained
      quality of life. Based on the phase I and II trial data, the US Food and Drug
      Administration granted approval of crizotinib in August 2011. The consistency of
      the crizotinib data to date suggests accurate selection of the target population
      for crizotinib treatment. The ability to molecularly select patients likely to
      respond to an investigational agent argues that future clinical development of
      targeted agents should be re-evaluated. Updated trial designs incorporating
      molecular testing, early use of enrichment biomarkers and intermediary endpoints
      may accelerate and optimise clinical evaluation of targeted agents. Such trial
      designs should allow rapid clinical evaluation, minimise exposure of patients to
      therapies unlikely to be of benefit and, potentially, allow accelerated drug
      approval in molecularly specified populations.

PMID- 22397765
TI  - Opposite effects of microchimerism on breast and colon cancer.
AB  - BACKGROUND: Detection of Y chromosome, thought to originate from previous
      pregnancies with a male fetus, is common in women. Lower concentrations have been
      reported in women with breast cancer than cancer-free women. Data in women with
      other types of cancer are sparse. The purpose of the study was to determine
      whether the lower concentrations predate cancer diagnosis, and whether a possible
      beneficial effect was specific to breast cancer. METHODS: We conducted a
      prospective case-cohort study of 50-64-year-old Danish women enrolled in the
      diet, cancer and health cohort. Blood samples and questionnaire data were
      obtained during 1993-1997 when all women were cancer-free. In 2006 all women were
      followed up for incident breast and colon cancer in national registers. In
      blinded analyses, we analysed buffy coat DNA for Y chromosome (DYS14) as a marker
      of male microchimerism. RESULTS: We detected male microchimerism in 70% of 272
      cancer-free women, 40% of 89 women who later developed breast cancer, and 90% of
      67 women who later developed colon cancer. The corresponding odds ratios were
      0.30 (95% confidence interval (CI) 0.17-0.52) for breast, and 3.9 (95%CI 1.6-9.5)
      for colon cancer. CONCLUSION: Detection of male microchimerism was strongly
      associated with reduced risk of developing breast cancer and also the increased
      risk of developing colon cancer. Confirmatory findings based on an improved study
      design, failure to identify important confounders and the strength of the
      associations lead us to believe that microchimerism may be highly relevant to
      later cancer development. However, the present study does not allow us to
      identify the underlying biological mechanisms.

PMID- 22397766
TI  - Discovery- and target-based protein quantification using iTRAQ and pulsed Q
      collision induced dissociation (PQD).
AB  - Pulsed Q collision-induced dissociation (PQD) was developed in part to facilitate
      detection of low-mass reporter ions using labeling reagents (e.g. iTRAQ) on LTQ
      platforms. It has generally been recognized that the scan speed and sensitivity
      of an LTQ are superior than those of an Orbitrap using the higher-energy
      collisional dissociation (HCD). However, the use of PQD in quantitative
      proteomics is limited, primarily due to the meager reproducibility of reporter
      ion ratios. Optimizations of PQD for iTRAQ quantification using LTQ have been
      reported, but a universally applicable strategy for quantifying the less abundant
      proteins has not been fully established. Adjustments of the AGC target, MUscan,
      or scan speed offer only incremental improvements in reproducibility. From our
      experience, however, satisfactory coefficients of variation (CVs) of reporter ion
      ratios were difficult to achieve using the discovery-based approach. As an
      alternative, we implemented a target-based approach that obviates data dependency
      to allow repetitive data acquisitions across chromatographic peaks. Such a
      strategy generates enough data points for more reliable quantification. Using
      cAMP treatment in S49 cell lysates and this target-based approach, we were able
      to validate differentially expressed proteins, which were initially identified as
      potential candidates using the discovery-based PQD. The target-based strategy
      also yielded results comparable to those obtained from HCD in an Orbitrap. Our
      findings should aid LTQ users who desire to explore iTRAQ quantitative proteomics
      but have limited access to the more costly Orbitrap or other instruments.

PMID- 22397769
TI  - Lactococcus garvieae multi-valve infective endocarditis in a traveler returning
      from South Korea.
AB  - Lactococcus garvieae is a rare but emerging human pathogen causing a variety of
      infections with only ten cases of infective endocarditis reported in the
      literature. We present the only case of Lactococcus garvieae infective
      endocarditis affecting both a native and a bioprosthetic valve in a traveler
      returning from rural South Korea.

PMID- 22397767
TI  - [Severe hypoplastic left heart syndrome: palliative care after prenatal
      diagnosis].
AB  - We analyzed 16 cases of hypoplastic left heart syndrome (HLHS) submitted to the
      multidisciplinary center at Rennes Teaching Hospital from 2006 to 2010 for
      prenatal diagnosis. The information given to parents at the moment of choice is
      capital for them to make their own decision: in our team the real choice for
      parents stands between termination of pregnancy (TOP) and palliative care (PC).
      The Norwood procedure is rarely proposed to parents in France and it is performed
      in very few centers. Heart transplant is never proposed nor done at this age. The
      objectives of our study were to understand the reasons for the choice of PC, take
      stock of our experience of PC, and relate the benefits but also the disadvantages
      of PC. Over the 16 patients whose fetus had HLHS, 9 requested TOP, while 7 others
      wanted to live their pregnancy and meet their child at birth, therefore
      requesting neonatal PC. No family asked for the Norwood procedure. Four children
      died within the first days (D1, D2, D4, D9), 2 others died at 5 and 7 months, 1
      child was operated on for coarctation of the aorta (unknown before birth) and is
      still alive 1.5 years later. Maternal motivations to continue the pregnancy were
      clearly described for 2 of the 7 cases: religious prohibition of TOP in 1 case,
      negative experiences of previous abortions in the second case. In another case,
      the parents hesitated between PC and Norwood surgery. For the other women, the
      reasons were less clearly expressed. In our series, HLHS is the first indication
      for PC from prenatal diagnosis (7/16 cases in the same period) while in the
      literature, heart diseases are the second cause of TOP after the neurological
      causes. The overrepresentation of this pathology in the families who opt for PC
      may be due to the unconscious image that both professionals and families have of
      HLHS: severity of an inevitably fatal disease, rapid postnatal death, and no
      suffering. Our study may change this view: a child was in fact carrying a curable
      defect which was discovered 12 days after birth, 2 children died at 5 and 7
      months, and 5 of 6 children had major analgesics at the end of life.
      Nevertheless, the families were supported and followed by the PC network, except
      1 who ruptured all contacts in a context of presumed intense suffering, but the
      other 6 do not regret their choice despite the difficulties.

PMID- 22397771
TI  - Gender reassignment surgery--a 13 year review of surgical outcomes.
AB  - PURPOSE: The aim of this study is to thoroughly report on surgical outcomes from
      332 patients who underwent male to female gender reassignment surgery (GRS).
      MATERIAL AND METHODS: Records from 332 patients who underwent GRS from 1995 to
      2008 were reviewed. All patients were submitted to penile inversion vaginoplasty
      with glans-derived sensate clitoroplasty. Mean age was 36.7 years (range 19-68
      years). Surgical complications were stratified in 5 main groups: genital region,
      urinary tract, gastrointestinal events, wound healing disorders and unspecific
      events. RESULTS: Progressive obstructive voiding disorder due to meatal stenosis
      was the main complication observed in 40% of the patients, feasibly corrected
      during the second setting. Stricture recurrence was found in 15%. Stricture of
      vaginal introitus was observed in 15% of the cases followed by 12% and 8% of
      vaginal stenosis and lost of vaginal depth, respectively. Rectal injury was seen
      in 3% and minor wound healing disorders in 33% of the subjects. CONCLUSION:
      Regarding male to female GRS, a review of the current literature demonstrated
      scarce description of complications and their treatment options. These findings
      motivated a review of our surgical outcomes. Results showed a great number of
      adverse events, although functionality preserved. Comparision of our outcomes
      with recent publications additionally showed that treatment options provide
      satisfying results. Moreover, outcomes reaffirm penile inversion vaginoplasty in
      combination with glans-derived sensate clitoroplasty as a safe technique.
      Nevertheless, discussing and improving surgical techniques in order to reduce
      complications and their influence on patient's quality of life is still strongly
      necessary and theme of our future reports.

PMID- 22397770
TI  - Unidirectional barbed suture versus standard monofilament for urethrovesical
      anastomosis during robotic assisted laparoscopic radical prostatectomy.
AB  - PURPOSE: V-LocTM180 (Covidien Healthcare, Mansfield, MA) is a new unidirectional
      barbed suture that may reduce loss of tension during a running closure. We
      evaluated the use of the barbed suture for urethrovesical anastomosis (UVA)
      during robotic assisted laparoscopic prostatectomy (RALP). Time to completion of
      UVA, post-operative anastomotic leak rate, and urinary incontinence were compared
      in patients undergoing UVA with 3-0 unidirectional-barbed suture vs. 3-0
      MonocrylTM (Ethicon, Somerville, NJ). MATERIALS AND METHODS: Data were
      prospectively collected for 70 consecutive patients undergoing RALP for prostate
      cancer between November 2009 and October 2010. In the first 35 patients, the UVA
      was performed using a modified running van Velthoven anastomosis technique using
      two separate 3-0 monofilament sutures. In the subsequent 35 patients, the UVA was
      performed using two running novel unidirectional barbed sutures. At 7-12 days
      postoperatively, all patients were evaluated with a cystogram to determine
      anastomotic integrity. Urinary incontinence was assessed at two months and five
      months by total daily pad usage. Clinical symptoms suggestive of bladder neck
      contracture were elicited. RESULTS: Age, PSA, Gleason score, prostate size,
      estimated blood loss, body mass index, and clinical and pathologic stage between
      the 2 groups were similar. Comparing the monofilament group and V-LocTM180
      cohorts, average time to complete the anastomosis was similar (27.4 vs. 26.4
      minutes, p = 0.73) as was the rate of urinary extravasation on cystogram (5.7 %
      vs. 8.6%, p = 0.65). There were no symptomatic bladder neck contractures noted at
      5 months of follow-up. At 2 months, the percentage of patients using 2 or more
      pads per day was lower in the V-LocTM180 cohort (24% vs. 44%, p < 0.02). At 5
      months, this difference was no longer evident. CONCLUSIONS: Time to complete the
      UVA was similar in the intervention and control groups. Rates of urine leak were
      also comparable. While the V-LocTM180 was associated with improved early
      continence, this difference was transient.

PMID- 22397772
TI  - Rapid thawing human sperm does not affect basic parameters in normozoospermic
      men: a double-blind prospective study.
AB  - PURPOSE: To compare sperm recovery from slow versus rapid thawing technique using
      thirty-eight normozoospermic human sperm samples, as follows. Twentyone samples
      from men taking part in routine infertility screening exams (infertile group) and
      seventeen from proven fertile volunteer men with at least one child (fertile
      group). MATERIALS AND METHODS: After analysis of motility, concentration, strict
      morphology and functional integrity of membranes, sperm was divided into two
      aliquots of 0.5 mL each and frozen in TyB-G medium. Samples were thawed at room
      temperature (25 +/- 2 degrees  C) for 25 minutes (slow thaw) or in a water bath
      at 75 degrees  C for 20 seconds followed by water bath at 37 degrees  C for 3
      minutes (rapid thaw). After thawing, motility, strict morphology and functional
      integrity of membranes were evaluated by a blinded investigator. The results were
      expressed as mean +/- standard deviation for parametric variables and analyzed
      using Student's t-test. Data with unpaired non-parametric variables were
      expressed as median (interquartile range) and analyzed by the Mann-Whitney test.
      Wilcoxon test was used to analyze non-parametric paired variables. RESULTS: There
      was no significant difference between techniques for total and progressive
      motility, percentage of normal morphological forms, hypoosmotic swelling test.
      CONCLUSIONS: Although the rapid thawing protocol was completed in a shorter time
      (three minutes and 20 seconds versus 25 minutes, respectively), it wasn't harmful
      since both techniques showed comparable spermatozoa recovery. Additional research
      is needed to confirm its safety in clinical research before introducing this
      methodology in routine assisted reproduction.

PMID- 22397773
TI  - Varicocele among healthy young men in Turkey; prevalence and relationship with
      body mass index.
AB  - AIM: Varicocele is characterized by abnormal tortuosity and dilatation of the
      veins of the pampiniform plexus within the spermatic cord and is one of the
      causes related to male infertility. This study aimed to investigate the
      correlation between varicocele and somatometric parameters. We also aimed to
      determine prevalence and treatment ratio of this disorder among healthy young
      Turkish men. MATERIALS AND METHODS: A total of 2061 young men aged from 19 to 34
      years was enrolled and cross sectionally evaluated for status of varicocele. Body
      mass index was calculated. Patients were categorized as normal weight, overweight
      and obese using by National Institutes of Health criteria. Patients underwent
      physical examinations for the presence and grade of varicocele. If the varicocele
      was found and previously submitted to different treatment modalities, the age of
      treatment and outcomes were recorded. RESULTS: Varicocele was present in 498 men
      (24.2%). The mean age of the participants was 22.7 +/- 1.8 years, and the median
      BMI was 22.8 +/- 2.0 kg/m2. There were no significant differences in age, height,
      weight and BMI among the patients with different grades of varicocele (p > 0.05).
      Although no significant difference was found in varicocele prevalence between
      normal weight and over-weight participants (p > 0.05), obese participants had
      significantly lower varicocele prevalence compared with normal or over weight
      participants (p = 0.006). A total of 49 men had scrotal pain and the treatment
      ratio was only 2.8%. CONCLUSION: Prevalence of varicocele was found in about 24%
      of healthy young Turkish population. Participants with varicocele had
      significantly lower BMI values compared with those without varicocele. Our
      findings supported the hypothesis that individuals with a greater BMI may have
      advantages in relieving the varicocele, but further studies are required to
      clarify this issue. Additionally treatment ratio was low among young men with
      varicocele.

PMID- 22397774
TI  - Three different techniques for administering analgesia during transrectal
      ultrasound-guided prostate biopsy: a comparative study.
AB  - PURPOSE: The efficacy of three different analgesic techniques during transrectal
      ultrasound (TRUS) guided prostate biopsy, including (i) periprostatic blockage
      (PPB), (ii) intrarectal gel instillation, and (iii) sedoanalgesia were compared.
      MATERIAL AND METHODS: During a period of five months, 100 consecutive men were
      enrolled in this study. A 10-point linear visual analogue scale (VAS) was used to
      assess the pain scores during (VAS 1), immediately after (VAS 2) and one hour
      after (VAS 3) the needle biopsy procedure. The relationship between the level of
      pain, prostate volume, age and PSA was determined. RESULTS: There were no
      statistically significant differences between the four groups in terms of mean
      age and PSA values. The pain scores were significantly lower in sedoanalgesia and
      PPB groups (p = 0.0001). There was no statistically significant difference
      between the groups in terms of complications. CONCLUSIONS: In this study, it was
      shown that patient comfort is better and it is possible to get decreased pain
      scores with PPB or sedoanalgesia. However, PPB is a preferable method in TRUS
      guided prostate biopsy since it is much more practical in outpatient clinics.

PMID- 22397775
TI  - Enhanced computed tomograms provide accurate assessment of local extension and
      stage of bladder carcinoma.

PMID- 22397776
TI  - Acute bilateral renal vein thrombosis secondary to sepsis from pyelonephritis.

PMID- 22397778
TI  - Development of a rabbit's urethral sphincter deficiency animal model for
      anatomical-functional evaluation.
AB  - OBJECTIVE: The aim of the study was to develop a new durable animal model (using
      rabbits) for anatomical-functional evaluation of urethral sphincter deficiency.
      MATERIALS AND METHODS: A total of 40 New Zealand male rabbits, weighting 2.500 kg
      to 3.100 kg, were evaluated to develop an incontinent animal model. Thirty-two
      animals underwent urethrolysis and 8 animals received sham operation. Before and
      at 2, 4, 8 and 12 weeks after urethrolysis or sham operation, it was performed
      cystometry and leak point pressure (LPP) evaluation with different bladder
      distension volumes (10, 20, 30 mL). In each time point, 10 animals (8 from the
      study group and 2 from the sham group) were sacrificed to harvest the bladder and
      urethra. The samples were evaluated by H&E and Masson 's Trichrome to determine
      urethral morphology and collagen/smooth muscle density. RESULTS: Twelve weeks
      after urethrolysis, it was observed a significant decrease in LPP regardless the
      bladder volume (from 33.7 +/- 6.6 to 12.8 +/- 2.2 cmH2O). The histological
      analysis evidenced a decrease of 22% in smooth muscle density with a proportional
      increase in the collagen, vessels and elastin density (p < 0.01). CONCLUSIONS:
      Transabdominal urethrolysis develops urethral sphincter insufficiency in rabbits,
      with significant decrease in LPP associated with decrease of smooth muscle fibers
      and increase of collagen density. This animal model can be used to test
      autologous cell therapy for stress urinary incontinence treatment.

PMID- 22397779
TI  - Increasing antibiotic resistance among uropathogens isolated during years 2006
      2009: impact on the empirical management.
AB  - Urinary tract infections (UTI) are one of the most common infections with an
      increasing resistance to antimicrobial agents. PURPOSE: Empirical initial
      antibiotic treatment of UTI must rely on susceptible data from local studies.
      MATERIALS AND METHODS: Retrospective analysis of isolated bacteria from children
      with UTIs was performed at the university hospital during years 2006-2009. The
      findings were compared with data collected in a similar study carried out in 2002
      2003. RESULTS: A total of 1439 uropathogens were isolated. Escherichia coli
      (E.coli) was the leading cause, followed by Enterobacter, and other gram negative
      bacilli. It was observed resistance of E.coli to ceftriaxone, cefexime, amikacin,
      gentamycin, and nalidixic acid; Enterobacter to cefexime; and the resistance of
      gram negative bacilli to gentamicin and cefexime increased significantly. The
      highest effective antibiotic was Imipenem, ciprofloxacin, and amikacin with
      96.7%, 95% and 91% sensitivity rates, respectively, followed by ceftriaxone
      77.2%, gentamicin 77%, nitrofurantoin 76.4%, nalidixic acid 74.3% and cefexime
      with 70%. CONCLUSION: The use of nitrofurantoin or nalidixic acid as initial
      empirical antibacterial therapy for cystitis seems appropriate. For cases of
      simple febrile UTI, the use of initial parenteral therapies with amikacin or
      ceftriaxone followed by an oral third generation cephalosporin also seemed
      appropriated, and in cases of severely ill patients or complicated UTI, imipenem
      as monotherapy or, a combination of Ceftriaxone with an aminoglycoside, are
      recommended.

PMID- 22397780
TI  - The final stage of the laparoscopic procedure: exploring final steps.
AB  - Despite significant advances in laparoscopic technique and technologies,
      laparoscopic Urologic surgery remains technically demanding regarding various
      surgical steps including the challenge of specimen retrieval and extraction,
      whether to install a drainage system and the best option for wound closure.
      Laparoscopic specimen entrapment and extraction occurs at what is falsely
      considered the "end of the procedure". During open surgery, after the specimen
      has been mobilized, the specimen is simply lifted out of the larger incision
      which has been made to achieve the surgical objectives. In contrast, significant
      laparoscopic skill is required to entrapand safely extract laparoscopic
      specimens. Indeed, the Urologist and surgical team which are transitioning from
      open surgery may disregard this important part of the procedure which may lead to
      significant morbidity. As such, it is imperative that during laparoscopic
      procedures, the "end of the procedure" be strictly defined as the termination of
      skin closure and dressing placement. Taking a few minutes to focus on safe
      specimen entrapment and extraction will substantially reduce major morbidity. The
      following review focus on the technology and technique of specimen entrapment and
      extraction, on the matter of whether to install a drainage system of the
      abdominal cavity and the options for adequate closure of trocar site wounds. This
      article 's primary objectives are to focus on how to minimize morbidity while
      maintain the advantages of a minimally invasive surgical approach.

PMID- 22397781
TI  - When prone position is contraindicated or not preferable, can supine percutaneous
      nephrolithotomy solve the problem?
AB  - PURPOSE: To assess safety and efficacy of supine percutaneous nephrolithotomy in
      patients for whom prone position or general anesthesia is contraindicated or not
      preferable due to associated comorbidities, overweight or ipsilateral upper
      ureteric calculi. MATERIALS AND METHODS: Fifty two patients (37 males and 15
      females, mean age 33 +/- 10.2 years) were included in this study. Supine position
      was selected due to anesthetic considerations (preexisting compromised
      cardiopulmonary status, morbid obesity (body mass index > 40 kg/m2) and/or other
      associated medical comorbidities), impossible prone position due to bone
      deformities or associated ipsilateral upper ureteric stone. Regional anesthesia
      was used in 24 patients while 28 patients underwent general anesthesia. After
      standard cystoscopy and retrograde ureteropyelography in the dorsal lithotomy
      position, the position was modified using 3 liters of saline bag below the
      ipsilateral upper flank. Percutaneous access to the pelvicalyceal system was
      performed through the posterior axillary line under fluoroscopic guidance.
      RESULTS: Successful renal puncture was achieved in all cases. Single access via
      the lower calyx was the most commonly used access (36 cases). Stone-free rate was
      92.3%. Postoperative complications classified according to Clavien Dindo
      classification included bleeding requiring transfusion (3.8%), prolonged fever
      (7.7%), deep venous thrombosis (1.9%) [grade II in all] and urinary leakage
      requiring ureteric stenting (5.8%) [grade IIIa]. CONCLUSIONS: The modified supine
      position for percutaneous nephrolithotomy is a safe and effective option that
      offers several advantages with an excellent outcome. It can be performed safely
      for morbidly obese patients and those with cardiopulmonary compromise.

PMID- 22397783
TI  - Retroperitoneal lymph node dissection with concomitant IVC thrombectomy, caval
      wall resection, and grafting for metastatic NSGCT.
AB  - INTRODUCTION: The management of a post-chemotherapy retroperitoneal mass
      secondary to testicular cancer can present a surgical challenge when involving
      adjacent organs or major vascular structures. We present the first video of a
      retroperitoneal lymph node dissection (RPLND) with IVC (inferior vena cava)
      thrombectomy, caval wall resection resulting from metastatic non-seminomatous
      germ cell testis (NSGCT) cancer. METHODS: In this surgical video, we highlight
      important surgical considerations in the management of a postchemotherapy
      retroperitoneal mass with direct IVC wall invasion and level 2 thrombus in such a
      patient. RESULTS: A 34 year old man underwent a right inguinal orchiectomy for a
      mixed NSGCT (embryonal, yolk sac, and teratoma components) and elevated serum
      tumor markers. He underwent systemic chemotherapy (BEP regimen x 4 cycles) with
      subsequent near normalization of tumor markers. His post-chemotherapy imaging
      revealed a 6 cm residual retroperitoneal mass with a level 2 IVC tumor thrombus
      and suspected direct infrarenal IVC wall invasion from the mass. The patient
      underwent an open post-chemotherapy RPLND, IVC thrombectomy, IVC resection and
      grafting. The final pathology report of the retroperitoneal mass revealed
      teratoma with no viable germ cell tumor elements and negative surgical margins.
      His intra-operative and post-operative stages were unremarkable with his IVC
      graft remaining patent and no evidence of disease recurrence at last follow-up.
      CONCLUSION: We present the first surgical video of a post-chemotherapy RPLND with
      IVC thrombectomy, caval wall resection and grafting for metastatic NSGCT. The
      final pathology report of teratoma with no viable tumor highlights the local
      vascular invasive potential of such pathology.

PMID- 22397782
TI  - Robot-assisted pyeloplasty: outcomes for primary and secondary repairs, a single
      institution experience.
AB  - INTRODUCTION: Robotic Pyeloplasty (RAP) is a technique for management of
      ureteropelvic junction obstruction (UPJO). PURPOSE: To report outcomes of RAP for
      primary and secondary (after failed primary treatment) UPJO. MATERIALS AND
      METHODS: Single institution data of adult RAP performed from 2007 to 2009 was
      collected retrospectively following approval by our IRB. Database analysis
      included patient age, race, pre and post-operative imaging studies and
      perioperative variables including operative time, blood loss, pain and
      complications. RESULTS: Fifty-five adult patients underwent RAP (26 left/29
      right) for UPJO including 9 secondary procedures from 2007 to 2009. Average
      follow-up was 16 months (1-36). Mean age was 41 years (18-71) with an average BMI
      of 27 (17-42); 32 were female. Most patients were diagnosed with preoperative
      diuretic renal scintigraphy and the obstructed side demonstrated mean function of
      41% and t1/2 of 70 minutes. Mean operative time was 194 minutes with average
      blood loss less than 100 mL. Mean hospital stay was 1.7 days with an average
      narcotic equivalent dose of 15 mg. RAP for secondary UPJO took longer with more
      blood loss and had a lower success rate. Failure was defined as the need of
      another procedure due to persistent pain and/or obstruction after diuretic renal
      imaging. One patient (2%) with primary UPJO failed and 2 patients (22%) with
      secondary UPJO failed. One major complication occurred. CONCLUSION: RAP is a good
      option for the treatment of patients with UPJO. Reported series have established
      that endopyelotomy has inferior success rate for the treatment of primary UPJO
      which compromises the success of subsequent treatment as demonstrated in our
      higher failure rate with secondary UPJO repair.

PMID- 22397784
TI  - Evaluation of Tadalafil effect on lower urinary tract symptoms of benign
      prostatic hyperplasia in patients treated with standard medication.
AB  - OBJECTIVES: To evaluate safety and efficacy of tadalafil on lower urinary tract
      symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in patients
      treated with standard medication. MATERIALS AND METHODS: In this case-controlled
      randomized clinical trial, from November 2008 to August 2009, 132 patients with
      obstructive and irritative urinary tract symptoms due to BPH, IPSS >= 8, no
      indication for surgical intervention and that reached plateau levels of response
      to treatment were selected. These patients were randomly allocated in two groups
      (each containing 66 patients). The treatment group received standard treatment of
      BPH and tadalafil (10 mg nightly); the placebo group received only standard
      treatment of BPH. IPSS, maximum urinary flow rate (Qmax) and quality of life were
      assessed before and after a 3-month period of study. RESULTS: Before treatment,
      mean IPSS, Qmax and quality of life values in the treatment and placebo groups
      were 13.06 +/- 4.37 and 13.66 +/- 4.25, 8.92 +/- 2.96 mL/s and 9.09 +/- 2.91
      mL/s, 2.93 +/- 0.86 and 2.66 +/- 0.78, respectively. After treatment, mean IPSS,
      Qmax, and quality of life values in treatment group were 7.66 +/- 3.99, 9.99 +/-
      4.76 mL/s and 1.80 +/- 0.98, respectively. These findings were compared to
      corresponding values of the placebo group (11.37 +/- 3.64, 8.73 +/- 2.22 mL/s and
      2.19 +/- 0.53, respectively): IPSS and quality of life were significantly
      different but Qmax didn't show a significant change. CONCLUSIONS: Tadalafil
      improves quality of life and urinary symptoms in patients with LUTS suggestive of
      BPH, but doesn't have any significant effect on Qmax. Therefore, this drug may be
      effectively used in combination with standard medical therapies for BPH.

PMID- 22397785
TI  - The fate of small renal masses, less then 1 cm size: outcome study.
AB  - PURPOSE: We evaluated the outcome and etiologies of small renal masses (less than
      1 cm in size) discovered incidentally on 2 consecutive CTs that investigated
      nonurologic abdominal complaints. MATERIALS AND METHODS: A retrospective search
      for incidentally discovered small renal masses, less then 1 cm in size, was
      carried out in the files of 6 major US medical centers. 4822 such lesions had
      been reported over a 12 year period. A search of these patients' records revealed
      1082 subsequent new CTs for non urologic complaints, allowing the assessment of
      the fate of the masses. Lesions enlarging, of ambivalent contour or enhancement
      were examined by a third multiphasic MDCT. The findings were interpreted by 2
      blinded radiologists. RESULTS: Six hundred and four masses could no longer be
      identified, 231 were significantly smaller, 113 unchanged in size and 134 larger.
      Of the disappearing lesions 448 were located in the medulla, 94 both in medulla
      and cortex and 62 in cortex. Multiphasic MDCTs obtained in 308 masses enlarging,
      unchanged in size or of ambivalent appearance, revealed 7 neoplasms, 45
      inflammatory lesions, 8 abscesses and 62 renal medullary necrosis. Concurrent
      antibiotic therapy of GI conditions may have caused some of the 496 lesions to
      disappear. CONCLUSION: It is questionable whether the small number of malignant
      neoplasms (0.4%), inflammatory lesions (5%) and renal medullary necrosis (6%)
      justify routine follow-up CTs and exposure to radiation. The delay in
      intervention in neoplastic lesions probably didn't influence tumor-free survival
      potential and clinical symptoms would soon have revealed inflammatory conditions.
      With exception of ambivalent lesions, clinical surveillance appears adequate.

PMID- 22397787
TI  - Single-session ureteroscopic pneumatic lithotripsy for the management of
      bilateral ureteric stones.
AB  - PURPOSE: In nowadays there is no consensus on single-session ureteroscopic
      lithotripsy (URSL) for the management of bilateral ureteric stones. The aim of
      this study was to evaluate efficacy and safety of single-session URSL in patients
      with bilateral ureteric stones. MATERIALS AND METHODS: 41 patients who have
      undergone bilateral single-session URSL were evaluted in this study. A 8/9.8 Fr
      Wolf semi-rigid ureteroscope was used for the procedures, and the stones were
      fragmented with pneumatic lithotripter. RESULTS: A high stone-free rate was
      achieved (90.2%) after single endoscopic procedure with a retreatment rate of
      9.8%. The procedure was most successful for distal ureteric stones with a 96.2%
      stone-free rate followed by middle ureteric stones with a 81.8% stone-free rate
      while the least success was achieved for proximal ureteric stones with a 77.7%
      stone-free rate (p < 0.05). A greater stone-free rate was obtained in those with
      stones less than 10 mm (93.7%) than in those with stones larger than 10 mm
      (77.7%) (p < 0.05). Ureteral perforation occurred in only one patient (2.4%). No
      long-term complication was observed in any patient. CONCLUSIONS: Bilateral single
      session URSL can be performed effectively and safely with a low complication rate
      in patients with bilateral ureteric stones. It can reduce the need of
      anaesthetics and hospital stay.

PMID- 22397786
TI  - Combination of gemcitabine and carboplatin in urothelial cancer patients unfit
      for cisplatin due to impaired renal or cardiac function.
AB  - PURPOSE: Combination of gemcitabine and carboplatin is the accepted treatment for
      metastatic urothelial cancer patients unfit for cisplatin-based chemotherapy.
      MATERIALS AND METHODS: Gemcitabine 1000 mg/m2 (days 1, 8) and carboplatin AUC-
      4.5 (day 1) were given every 21 days to 23 patients with creatinine clearance <
      60 mL/min, cardiac ejection fraction < 45% or active ischemia. Patient
      characteristics included: median age 73 (56-86) years; primary site: bladder 17
      (73%), upper tract 6 (27 %) patients; Bajorin 's prognostic groups: good 6 (26%),
      intermediate 11 (48%) and poor 6 (26%) patients. Data was retrospectively
      documented. Patients were followed until they expired. RESULTS: We obtained
      objective responses in 8 (34.7%) patients, (95% CI, 16.3-57.2%), including one
      patient with complete response. The median progressionfree survival was 4 (0.2
      16.5+) months and the overall survival 8.6 (0.2-45.3+) months. At time of
      analysis, 4 patients (17%) remained disease free; 3 of them underwent resection
      of residual disease. Toxicity included: infection in 9 (39%) patients; among
      them, one died from pneumonia; bleeding >= grade 2 in 3 (13%) patients and
      fatigue grade 3 in 2 (9%) patients. Hematologic toxicity included grade 4
      thrombocytopenia in 2 (9%) patients and grade 4 neutropenia in 3 (13%) patients.
      Five (22%) patients discontinued therapy due to toxicity. CONCLUSIONS:
      Combination of gemcitabine and carboplatin demonstrated clinical activity in
      patients with advanced urothelial cancer unfit for cisplatin. It was associated
      with considerable toxicity. Resection of residual disease is feasible in this
      population.

PMID- 22397788
TI  - Robotic-assisted laparoscopic partial nephrectomy: initial experience in Brazil
      and a review of the literature.
AB  - CONTEXT AND PURPOSE: Partial nephrectomy has become the standard of care for
      renal tumors less than 4 cm in diameter. Controversy still exists, however,
      regarding the best surgical approach, especially when minimally invasive
      techniques are taken into account. Robotic-assisted laparoscopic partial
      nephrectomy (RALPN) has emerged as a promising technique that helps surgeons
      achieve the standards of open partial nephrectomy care while offering a minimally
      invasive approach. The objective of the present study was to describe our initial
      experience with robotic-assisted laparoscopic partial nephrectomy and extensively
      review the pertinent literature. MATERIALS AND METHODS: Between August 2009 and
      February 2010, eight consecutive selected patients with contrast enhancing renal
      masses observed by CT were submitted to RALPN in a private institution. In
      addition, we collected information on the patients ' demographics, preoperative
      tumor characteristics and detailed operative, postoperative and pathological
      data. In addition, a PubMed search was performed to provide an extensive review
      of the robotic-assisted laparoscopic partial nephrectomy literature. RESULTS:
      Seven patients had RALPN on the left or right sides with no intraoperative
      complications. One patient was electively converted to a robotic-assisted radical
      nephrectomy. The operative time ranged from 120 to 300 min, estimated blood loss
      (EBL) ranged from 75 to 400 mL and, in five cases, the warm ischemia time (WIT)
      ranged from 18 to 32 min. Two patients did not require any clamping. Overall, no
      transfusions were necessary, and there were no intraoperative complications or
      adverse postoperative clinical events. All margins were negative, and all
      patients were disease-free at the 6-month follow-up. CONCLUSIONS: Robotic
      assisted laparoscopic partial nephrectomy is a feasible and safe approach to
      small renal cortical masses. Further prospective studies are needed to compare
      open partial nephrectomy with its minimally invasive counterparts.

PMID- 22397790
TI  - Nursing: there's never been a better time...

PMID- 22397789
TI  - Simplified hemostatic technique during laparoscopic partial nephrectomy.
AB  - INTRODUCTION: Laparoscopic partial nephrectomy (LPN) has gained popularity in
      recent years, although it remains a challenging procedure. Herein we describe our
      technique of renal defect closure using sutures as the sole means of hemostasis
      during LPN. SURGICAL TECHNIQUE: The kidney is approached transperitoneally in a
      standard fashion. After the renal artery is clamped and the tumor has been
      excised, the defect is closed in two separate knot-free suture layers. The deep
      layer suture is continuous and involves deep parenchyma including the collecting
      system, if opened. The superficial layer suture approximates the margins of the
      defect using absorbable clips on one parenchymal edge only. No bolsters, glues or
      other additional hemostatic agents are used. RESULTS: At present this technique
      was applied in 34 patients. Tumor size ranged from 17-85 mm. Median warm ischemia
      time was 23 min (range 12-45) and estimated blood loss 55 mL (30-1000). There
      were no intraoperative complications or conversions to open surgery. No urine
      leaks or postoperative bleedings were observed. CONCLUSIONS: This simplified
      technique appears reliable and quick, and therefore may be attractive for many
      urologic surgeons. Furthermore, the avoidance of routine use of additional
      hemostatic maneuvers may provide an economical advantage to this approach with no
      compromise of the surgical outcome.

PMID- 22397791
TI  - Hemolytic disease of the newborn caused by anti-Wright (anti-Wra): case report
      and review of literature.
AB  - Antibodies to red cell antigens that are found at low frequency in the general
      population are rare causes of hemolytic disease of the newborn. To understand how
      to detect these cases, we provide a basic review of routine antenatal maternal
      antibody testing and report a case of a neonate with severe HDN caused by anti
      Wright (anti-Wra), successfully managed with transfusion, phototherapy, and high
      dose intravenous immunoglobulin. When hemolysis in a newborn is suspected in the
      absence of major blood group incompatibility or commonly detected maternal red
      cell antibodies, a direct antiglobulin test should be performed. A positive DAT
      should alert the clinician to the presence of maternal antibodies against low
      incidence antigens. Antibodies to the Wra antigen are one such rare cause of HDN.

PMID- 22397792
TI  - Quality improvement for neonatal nurses, part I: a framework for advancing the
      quality and safety of care.
AB  - Quality improvement (QI) and patient safety are becoming increasingly powerful
      drivers for health care planning and delivery. In this two-part series, the
      concept of QI will be introduced and implications for neonatal nursing care will
      be discussed. Part I reviews trends in the fields of QI and patient safety and
      introduces how neonatal practitioners are currently taking up QI and patient
      safety in their practice. Part II, to come, is titled "Using a Plan-Do-Study-Act
      Process to Introduce a Step-wise Framework for Establishing Oral Feeds in
      Premature Infants" will present the QI process "in action" by describing a QI
      project conducted in a Level III NICU on introducing and testing a new process
      for improving the transition from tube to oral feeding for preterm infants.

PMID- 22397793
TI  - Neonatal care in a Japanese NICU: notes based on a site visit.
AB  - This article presents an overview of a neonatal intensive care unit along with
      resuscitative care and management of the 22 to 23 weeks gestational age infant is
      as it was noted during a visit to the NICU of a large academic center in Japan.
      Non-English speaking neonatology communities may be at a disadvantage of having
      their research and practices well known in the English speaking ones. Thus,
      visits such as this are beneficial in exchanging ideas and practices that may
      ultimately be mutually beneficial in reducing mortality and morbidity in a
      specific category of neonates.

PMID- 22397794
TI  - A review of the management of intersex.
AB  - The birth of an individual with a blend of both male and female internal or
      external genitalia is known as an intersex condition. The incidence of genital
      anomalies is estimated to occur in 1 in 4,500 live births. Each intersex
      condition is determined by the external genital appearance, internal genital
      structures, and fertility potential. The main concept involved in the management
      of intersex is the establishment of an experienced multidisciplinary team.
      Management of intersex conditions is complex and involves a person's gender
      identity, gender role behavior, sexual orientation, sexual functioning, and
      psychological adjustment. This review will outline the management of intersex in
      the light of the latest research. We focus on diagnosis, surgical techniques, and
      the psychological aspects that are encountered in the management of intersex.

PMID- 22397795
TI  - Growth curves and z-scores: sorting it all out.
AB  - "How much does my baby weigh?" and "How long is my baby?" are two of the most
      frequently asked questions in the delivery room. From that point on, growth is
      followed closely by parents and primary care providers alike. Anthropomorphic
      measurements (height/length, weight, head circumference) are obtained routinely
      and are compared with standardized references to follow the growth pattern
      compared with the norm.

PMID- 22397796
TI  - Antibiotic resistance in the NICU.
AB  - Antimicrobial treatment is a mainstay therapy in the neo-natal intensive care
      unit (NICU). Given the lack of specificity for clinical symptoms of infection in
      the newborn and the overwhelming impact of infection with rapid multisystem
      dissemination, NICU providers tend to treat early while awaiting laboratory
      results. With the high vulnerability of our special population to a variety of
      potential infecting microbes, a combination of antibiotics is preferred for
      initial treatment. The selection of these antibiotics is based on the known or
      presumed environment of exposure. If the newborn is within a week of birth, we
      can reasonably expect the likely environment of exposure is the community or the
      mother. If the newborn is older or has undergone numerous procedures, we can
      presume the exposure is more likely to be hospital-based.

PMID- 22397797
TI  - Communication and collaboration technologies.
AB  - This is the third in a series of columns exploring health information technology
      (HIT) in the neonatal intensive care unit (NICU). The first column provided
      background information on the implementation of information technology throughout
      the health care delivery system, as well as the requisite informatics
      competencies needed for nurses to fully engage in the digital era of health care.
      The second column focused on information and resources to master basic computer
      competencies described by the TIGER initiative (Technology Informatics Guiding
      Education Reform) as learning about computers, computer networks, and the
      transfer of data.1 This column will provide additional information related to
      basic computer competencies, focusing on communication and collaboration
      technologies. Computers and the Internet have transformed the way we communicate
      and collaborate. Electronic communication is the ability to exchange information
      through the use of computer equipment and software.2 Broadly defined, any
      technology that facilitates linking one or more individuals together is a
      collaborative tool. Collaboration using technology encompasses an extensive range
      of applications that enable groups of individuals to work together including e
      mail, instant messaging (IM ), and several web applications collectively referred
      to as Web 2.0 technologies. The term Web 2.0 refers to web applications where
      users interact and collaborate with each other in a collective exchange of ideas
      generating content in a virtual community. Examples of Web 2.0 technologies
      include social networking sites, blogs, wikis, video sharing sites, and mashups.
      Many organizations are developing collaborative strategies and tools for
      employees to connect and interact using web-based social media technologies.3.

PMID- 22397798
TI  - The role of magnesium sulfate in the prevention of cerebral palsy.
AB  - Magnesium sulfate (MgSO4) has been widely used in the perinatal arena for many
      decades. It has been used for tocolysis in the U.S. for more than 60 years.
      Estimations of MgSO4 use for preterm labor (less than 34 weeks of gestation) run
      as high as 80 percent. Magnesium sulfate is a smooth, skeletal, and cardiac
      muscle depressant. It is used for preterm labor because of its potential to
      decrease muscle contractility by interfering with calcium uptake in the cells.
      Thousands of moms and babies have been exposed to this medication even though
      tocolysis remains an off-label use, the exact mechanism of action is not
      completely understood, and there are studies that show that it is ineffective for
      this indication, and no evidence that it improves perinatal outcomes.1-3
      Additionally, it is a high alert medication because of its narrow therapeutic
      window and the risk of causing an immediate life-threatening condition (acute
      respiratory failure) if an error in administration occurs.4.

PMID- 22397802
TI  - A qualitative exploration of the "critical window": factors affecting Australian
      children's after-school physical activity.
AB  - BACKGROUND: The after-school period is potentially a "critical window" for
      promoting physical activity in children. The purpose of this study was to
      qualitatively explore children's perceptions of the factors influencing their
      engagement in physical activity during the after-school period as the first phase
      in the development of a questionnaire. METHODS: Fifty-four South Australian
      children age 10-13 years participated in same gender focus groups. Transcripts,
      field notes, and activity documents were analyzed using content analysis. Through
      an inductive thematic approach, data were coded and categorized into perceived
      barriers and facilitators according to a social ecological model. RESULTS:
      Children identified a number of factors, including safety in the neighborhood and
      home settings, distance to and from places, weather, availability of time,
      perceived competence, enjoyment of physical activity, peer influence, and parent
      influence. New insights into bullying and teasing by peers and fear of dangerous
      animals and objects were revealed by the children. CONCLUSIONS: In this study,
      hearing children's voices allowed the emergence of factors which may not be
      exposed using existing surveys. These findings are grounded in children's
      perceptions and therefore serve as a valuable contribution to the existing
      literature, potentially leading to improved intervention and questionnaire
      design.

PMID- 22397801
TI  - Clinical trial designs for testing biomarker-based personalized therapies.
AB  - BACKGROUND: Advances in molecular therapeutics in the past decade have opened up
      new possibilities for treating cancer patients with personalized therapies, using
      biomarkers to determine which treatments are most likely to benefit them, but
      there are difficulties and unresolved issues in the development and validation of
      biomarker-based personalized therapies. We develop a new clinical trial design to
      address some of these issues. The goal is to capture the strengths of the
      frequentist and Bayesian approaches to address this problem in the recent
      literature and to circumvent their limitations. METHODS: We use generalized
      likelihood ratio tests of the intersection null and enriched strategy null
      hypotheses to derive a novel clinical trial design for the problem of advancing
      promising biomarker-guided strategies toward eventual validation. We also
      investigate the usefulness of adaptive randomization (AR) and futility stopping
      proposed in the recent literature. RESULTS: Simulation studies demonstrate the
      advantages of testing both the narrowly focused enriched strategy null hypothesis
      related to validating a proposed strategy and the intersection null hypothesis
      that can accommodate to a potentially successful strategy. AR and early
      termination of ineffective treatments offer increased probability of receiving
      the preferred treatment and better response rates for patients in the trial, at
      the expense of more complicated inference under small-to-moderate total sample
      sizes and some reduction in power. LIMITATIONS: The binary response used in the
      development phase may not be a reliable indicator of treatment benefit on long
      term clinical outcomes. In the proposed design, the biomarker-guided strategy
      (BGS) is not compared to 'standard of care', such as physician's choice that may
      be informed by patient characteristics. Therefore, a positive result does not
      imply superiority of the BGS to 'standard of care'. The proposed design and tests
      are valid asymptotically. Simulations are used to examine small-to-moderate
      sample properties. CONCLUSION: Innovative clinical trial designs are needed to
      address the difficulties and issues in the development and validation of
      biomarker-based personalized therapies. The article shows the advantages of using
      likelihood inference and interim analysis to meet the challenges in the sample
      size needed and in the constantly evolving biomarker landscape and genomic and
      proteomic technologies.

PMID- 22397803
TI  - Threshold measurements by self-fitting hearing aids: feasibility and challenges.
AB  - A self-fitting, self-contained hearing aid is a device that can be managed
      entirely by the user, without assistance from a hearing health care professional
      or the need for special equipment. A key component of such a device is an
      automated audiometer that will enable the user to self-administer measurements of
      in situ thresholds, which the hearing aid will use to prescribe a baseline
      setting for the wearer. The success of the device therefore depends on the
      validity and reliability of in situ threshold measurements and automatically
      measured thresholds. To produce a complete and self-contained device, the self
      fitting hearing aid will also enable identification of audiograms that are
      contraindicative of hearing aid usage. The feasibility and challenges of
      achieving these characteristics are explored and discussed. While the overall
      concept seems feasible, several challenges were identified that need thorough
      investigation and/or development. These include the use of instructions to self
      manage hearing aid insertion and in situ threshold measurements, selection of an
      appropriate transducer and instant-fit tip that will allow measurements of a wide
      range of threshold levels, control of ambient noise during threshold
      measurements, and self-manageable procedures that enable identification of such
      audiogram characteristics as asymmetry and conductive hearing loss.

PMID- 22397804
TI  - Biopsies from one tumour have more genetic differences than similarities, finds
      study.

PMID- 22397807
TI  - Temperature-dependent Raman study of thermal parameters in CdS quantum dots.
AB  - We  report  on the strong temperature-dependent thermal expansion, alpha(D), in
      CdS quantum dots (QDs) embedded in a glass template. We have performed a
      systematic study by using the temperature-dependent first-order Raman spectra, in
      CdS bulk and in dot samples, in order to assess the size dependence of alpha(D),
      and where the role of the compressive strain provoked by the glass host matrix on
      the dot response is discussed. We report the Gruneisen mode parameters and the
      anharmonic coupling constants for small CdS dots with mean radius R ~ 2.0 nm. We
      found that gamma parameters change, with respect to the bulk CdS, in a range
      between 20 and 50%, while the anharmonicity contribution from two-phonon decay
      channel becomes the most important process to the temperature-shift properties.

PMID- 22397808
TI  - Immune status is more affected by age than by carotenoid depletion-repletion in
      healthy human subjects.
AB  - Prospective studies have indicated an age-related impairment of the immune
      response. Carotenoids have been hypothesised to enhance immune cell function. The
      aim of the present study was to describe the age-related effects and the impact
      of in vivo dietary carotenoid depletion and repletion on specific and non
      specific immunity. A total of ninety-eight healthy male subjects (aged 20-75
      years) received a carotenoid-depleted diet for 3 weeks and were then supplemented
      daily for 5 weeks with 30 mg beta-carotene, 15 mg lycopene and 9 mg lutein. Blood
      samples were collected at study entry, after depletion and supplementation, and
      biomarkers of immune status were determined. We found that serum IgA levels were
      positively correlated with ageing. Lymphocyte phenotyping indicated an increase
      with age in the memory T-helper cell subpopulation (CD4+CD45RO+) concomitantly
      with a decrease in naive T-helper cells (CD4+CD45RA+). A significant increase in
      the natural killer cells subpopulation and a small decrease in B lymphocytes were
      also observed, especially for the oldest volunteers. From ex vivo cell function
      exploration, a positive correlation was observed between age and IL-2 production
      of phytohaemagglutinin-stimulated lymphocytes. Neutrophils' bactericidal activity
      was significantly impaired with age (from 50 years) and was modulated by
      carotenoid status. An age effect was found on neutrophils' spontaneous migration
      but not on directed migration. Immune response in healthy human subjects is
      mostly affected by age rather than by dietary carotenoid depletion and repletion.
      Even in carefully selected healthy volunteers, some age-related immune changes
      occur predominantly from 50 years onwards. This immunosenescence could generate a
      loss in the immune system adjustment capacity.

PMID- 22397810
TI  - Perspectives on physical activity and exercise among Appalachian youth.
AB  - BACKGROUND: Most children in the United States receive far less physical activity
      (PA) than is optimal. In rural, under resourced areas of Appalachian Kentucky,
      physical inactivity rates are significantly higher than national levels. We
      sought to understand children's perceptions of PA, with the goal of developing
      culturally appropriate programming to increase PA. METHODS: During 11 focus
      groups, we explored perspectives on PA among 63 Appalachian children, ages 8-17.
      Sessions were tape recorded, transcribed, content analyzed, and subjected to
      verification procedures. RESULTS: Several perspectives on PA emerged among these
      rural Appalachian youth, including the clear distinction between PA (viewed as
      positive) and exercise (viewed as negative) and an emphasis on time and resource
      factors as barriers to adequate PA. Additional PA determinants expressed in the
      focus groups are similar to those of other populations. We include children's
      recommendations for appealing PA programs. CONCLUSIONS: Appalachian and other
      rural residents contend with the loss of rural health advantages (due to declines
      in farming/other occupational and avocational transitions). At the same time,
      Appalachian residents have not benefitted from urban PA facilitators (sidewalks,
      recreational facilities, clubs and organized leisure activities). Addressing low
      PA levels requires extensive community input and creative programming.

PMID- 22397809
TI  - Crowdsourced health research studies: an important emerging complement to
      clinical trials in the public health research ecosystem.
AB  - BACKGROUND: Crowdsourced health research studies are the nexus of three
      contemporary trends: 1) citizen science (non-professionally trained individuals
      conducting science-related activities); 2) crowdsourcing (use of web-based
      technologies to recruit project participants); and 3) medicine 2.0 / health 2.0
      (active participation of individuals in their health care particularly using web
      2.0 technologies). Crowdsourced health research studies have arisen as a natural
      extension of the activities of health social networks (online health interest
      communities), and can be researcher-organized or participant-organized. In the
      last few years, professional researchers have been crowdsourcing cohorts from
      health social networks for the conduct of traditional studies. Participants have
      also begun to organize their own research studies through health social networks
      and health collaboration communities created especially for the purpose of self
      experimentation and the investigation of health-related concerns. OBJECTIVE: The
      objective of this analysis is to undertake a comprehensive narrative review of
      crowdsourced health research studies. This review will assess the status, impact,
      and prospects of crowdsourced health research studies. METHODS: Crowdsourced
      health research studies were identified through a search of literature published
      from 2000 to 2011 and informal interviews conducted 2008-2011. Keyword terms
      related to crowdsourcing were sought in Medline/PubMed. Papers that presented
      results from human health studies that included crowdsourced populations were
      selected for inclusion. Crowdsourced health research studies not published in the
      scientific literature were identified by attending industry conferences and
      events, interviewing attendees, and reviewing related websites. RESULTS:
      Participatory health is a growing area with individuals using health social
      networks, crowdsourced studies, smartphone health applications, and personal
      health records to achieve positive outcomes for a variety of health conditions.
      PatientsLikeMe and 23andMe are the leading operators of researcher-organized,
      crowdsourced health research studies. These operators have published findings in
      the areas of disease research, drug response, user experience in crowdsourced
      studies, and genetic association. Quantified Self, Genomera, and DIYgenomics are
      communities of participant-organized health research studies where individuals
      conduct self-experimentation and group studies. Crowdsourced health research
      studies have a diversity of intended outcomes and levels of scientific rigor.
      CONCLUSIONS: Participatory health initiatives are becoming part of the public
      health ecosystem and their rapid growth is facilitated by Internet and social
      networking influences. Large-scale parameter-stratified cohorts have potential to
      facilitate a next-generation understanding of disease and drug response. Not only
      is the large size of crowdsourced cohorts an asset to medical discovery, too is
      the near-immediate speed at which medical findings might be tested and applied.
      Participatory health initiatives are expanding the scope of medicine from a
      traditional focus on disease cure to a personalized preventive approach.
      Crowdsourced health research studies are a promising complement and extension to
      traditional clinical trials as a model for the conduct of health research.

PMID- 22397811
TI  - Health labelling can influence taste perception and use of table salt for reduced
      sodium products.
AB  - OBJECTIVE: To investigate the effect of front-of-pack labels on taste perception
      and use of table salt for currently available and sodium-reduced soups. DESIGN:
      Within-subject design. SETTING: Sensory laboratory. SUBJECTS: Participants (n 50,
      mean age 34.8 (sd 13.6) years) were randomly served nine soups (250 ml each)
      across 3 d. Servings differed in: (i) health label (i.e. no health label, reduced
      salt label or Heart Foundation Tick); and (ii) sodium reduction (no reduction -
      benchmark, 15 % less sodium or 30 % less sodium). Before tasting, participants
      rated their expected salt intensity and liking. After tasting, participants rated
      their perceived salt intensity and liking, after which they could add salt to the
      soup to make it more palatable. RESULTS: Reduced-salt labels generated a negative
      taste expectation and actual taste experience in terms of liking (P < 0.05) and
      perceived saltiness (P < 0.05). Perceived saltiness of sodium-reduced soups
      decreased more (P < 0.05), and consumers added more salt (P < 0.05), when soups
      carried the reduced-salt label. The tick logo and soups without health labels had
      no such influence on taste perception. CONCLUSIONS: Emphasizing salt reduction by
      means of a front-of-pack label can have a negative effect on taste perception and
      salt use, especially when consumers are able to taste differences between their
      regular soup and the sodium-reduced soup. Overall health logos which do not
      emphasize the reduction in salt are less likely to affect perceived salt
      intensity and therefore are viable solutions to indicate the healthiness of
      sodium-reduced products.

PMID- 22397812
TI  - Compared growth mechanisms of Zn-polar ZnO nanowires on O-polar ZnO and on
      sapphire.
AB  - Controlling the growth of zinc oxide nanowires is necessary to optimize the
      performance of nanowire-based devices such as photovoltaic solar cells, nano
      generators, or light-emitting diodes. With this in mind, we investigate the
      nucleation and growth mechanisms of ZnO nanowires grown by metalorganic vapor
      phase epitaxy either on O-polar ZnO or on sapphire substrates. Whatever the
      substrate, ZnO nanowires are Zn-polar, as demonstrated by convergent beam
      electron diffraction. For growth on O-polar ZnO substrate, the nanowires are
      found to sit on O-polar pyramids. As growth proceeds, the inversion domain
      boundary moves up in order to remain at the top of the O-polar pyramids. For
      growth on sapphire substrates, the nanowires may also originate from the
      sapphire/ZnO interface. The presence of atomic steps and the non-polar character
      of sapphire could be the cause of the Zn-polar crystal nucleation on sapphire,
      whereas it is proposed that the segregation of aluminum impurities could account
      for the nucleation of inverted domains for growth on O-polar ZnO.

PMID- 22397813
TI  - On the temperature stability of extracellular hemoglobin of Glossoscolex
      paulistus, at different oxidation states: SAXS and DLS studies.
AB  - Glossoscolex paulistus hemoglobin (HbGp) was studied by dynamic light scattering
      (DLS) and small angle X-ray scattering (SAXS). DLS melting curves were measured
      for met-HbGp at different concentrations. SAXS temperature studies were performed
      for oxy-, cyanomet- and met-HbGp forms, at several pH values. At pH 5.0 and 6.0,
      the scattering curves are identical from 20 to 60  degrees C, and Rg is 108 A,
      independent of the oxidation form. At pH 7.0, protein denaturation and
      aggregation occurs above 55  degrees C and 60  degrees C, for oxy and met-HbGp,
      respectively. Cyanomet-HbGp, at pH 7.0, is stable up to 60  degrees C. At
      alkaline pH (8.0-9.0) and higher temperature, an irreversible dissociation
      process is observed, with a decrease of Rg, Dmax and I(0). Analysis by p(r),
      obtained from GNOM, and OLIGOMER, was used to fit the SAXS experimental
      scattering curves by a combination of theoretical curves obtained for HbLt
      fragments from the crystal structure. Our results show clearly the increasing
      contribution of smaller molecular weight fragments, as a function of increasing
      pH and temperature, as well as, the order of thermal stabilities: cyanomet->oxy
      >met-HbGp.

PMID- 22397814
TI  - The effect of strength training, recreational soccer and running exercise on
      stretch-shortening cycle muscle performance during countermovement jumping.
AB  - The purpose of the present study was to evaluate the effect of contrasting
      training modalities on mechanical muscle performance and neuromuscular activity
      during maximal SSC (stretch-shortening cycle) countermovement jumps (CMJ).
      Bilateral countermovement jumping, surface electromyography (EMG) and muscle
      fiber size (CSA) were studied in untrained individuals (n=49, 21-45 yrs) pre and
      post 12 weeks of progressive heavy-resistance strength training (ST, n=8),
      recreational soccer training (SOC, n=15), high-intensity interval running (INT,
      n=7), continuous running (RUN, n=9) or continuation of an inactive life-style
      (CON, n=10). ST displayed shortened CMJ take-off time (p<.05) and increased
      (p<.05) maximal CMJ jump height, peak down- and upward velocity of center of mass
      (COM), rate of vertical force development (RFD: DeltaF(Z)/Deltat), peak power
      production, rate of power development (RPD), mean plantar flexor EMG and peak
      hamstring rate of EMG rise (RER). Peak quadriceps EMG rate of rise increased in
      SOC (p<.05). Moreover, ST and SOC demonstrated increased quadriceps muscle fiber
      CSA and lean leg mass. Positive relationships (r>.70) were observed following ST
      between training-induced changes in CMJ SSC muscle performance, neuromuscular
      activity and muscle fiber CSA, respectively. ST induced a more rapid CMJ take-off
      phase and elevated muscle power production, indicating a more explosive-type SSC
      muscle performance. No effects were detected in CMJ performance after continuous
      running, high-intensity interval running and recreational soccer, despite an
      increased muscle fiber CSA and quadriceps muscle activity in SOC. Enhanced
      neuromuscular activity in the hip extensors (hamstrings) and plantar flexors, and
      increased myofiber fiber size were responsible for the enhanced CMJ SSC muscle
      performance with ST.

PMID- 22397815
TI  - The effects of short-term genistein intervention on prostate biomarker expression
      in patients with localised prostate cancer before radical prostatectomy.
AB  - Nutritionally relevant levels of genistein, the predominant isoflavone in
      soyabean associated with lower risk of prostate cancer (PCa), may modulate the
      expression of prostate tissue biomarkers associated with cancer prediction and
      progression. A phase 2 placebo-controlled, randomised, double-blind clinical
      trial was conducted in forty-seven Norwegian patients before prostatectomy.
      Intervention was 30 mg genistein or placebo capsules daily for 3-6 weeks. Luminal
      cells from malignant and benign glands were isolated with laser capture
      microdissection and the mRNA levels of androgen-related biomarkers (androgen
      receptor, NK3 homeobox 1, kallikrein-related peptide 4 (KLK4)) and cell cycle
      related genes (p21 Waf1/Cip1 , p27 Kip1 , p53) were analysed with real-time
      semiquantitative PCR. Immunohistochemistry of androgen-, cell cycle-,
      proliferative- (Ki67 nuclear antigen), apoptotic- (B-cell CLL/lymphoma 2 (BCL-2)
      and BCL-2-associated X protein) and neuroendocrine differentiation-related
      biomarkers (neuron-specific enolase and cytoplasmic chromogranin A) was performed
      using tissue microarrays containing normal, Gleason grade 3 and grade 4 prostate
      tissues. There were no significant effects by genistein intervention on
      proliferation-, cell cycle-, apoptosis- or neuroendocrine biomarkers. Genistein
      intervention, however, significantly reduced the mRNA level of KLK4 in tumour
      cells (P = 0.033) and there was a non-significant reduction in androgen and cell
      cycle-related biomarkers, except for p27Kip1, whose expression in the nuclear
      compartment was increased. Genistein intervention modulated the expression of
      several biomarkers which may be related to PCa prediction and progression. The
      present study supports genistein as a chemopreventive agent in PCa. Further
      investigation is warranted in larger and longer-duration studies.

PMID- 22397816
TI  - Analysis of fouling mechanisms in anaerobic membrane bioreactors.
AB  - In this paper, we investigate the fouling mechanisms responsible for MF and UF
      membrane flux decline in Anaerobic Membrane Bioreactors (AnMBR). We have used the
      fouling mechanism models proposed by Hermia (1982), namely pore constriction,
      cake formation, complete blocking and intermediate blocking. Based on an
      optimization approach and using experimental data extracted from the literature,
      we propose a systematic procedure for identifying the most likely fouling
      mechanism in play. Short-term as well as long-term experiments are considered and
      discussed. It was found that short-term experiments are usually characterized by
      two fouling phases during which the same fouling mechanism or two different
      mechanisms affect the process. In contrast, in long-term experiments involving
      cleaning cycles, membrane fouling appears to be better ascribed to one phase
      only. The impact of abiotic parameters on membrane fouling mechanisms is reviewed
      and discussed in the light of these results. Finally, it is shown that the
      mechanism most responsible for membrane fouling in an AnMBR is cake formation.
      This main result will be useful for the future development of simple integrated
      models for optimization and control.

PMID- 22397817
TI  - Freezing of gait in Parkinson's disease: further insights into pathophysiological
      mechanisms.
AB  - INTRODUCTION: Freezing of gait in Parkinson's disease (PD) was found to occur in
      the presence of the sequence effect (a decrease in length of consecutive
      footsteps) and a shortened step length. Gait asymmetry and reduced coordination
      of gait have also been implicated in freezing of gait. The aim of this study was
      to determine the effect of controlling for step length on asymmetry and
      coordination of gait. A second aim was to determine if asymmetry and bilateral
      coordination predicted freezing. METHODS: Data for sixteen participants with PD
      and freezing of gait, ten people with PD but no history of freezing and ten
      controls was analyzed. Participants, in their 'off' state, had their gait
      recorded walking at preferred and normalized step lengths of 100%, 75%, 50% and
      25%. RESULTS: Asymmetry of swing time increased in all groups as step length
      decreased from 100% to 25% and did not differ between the PD group with freezing
      compared to the PD group without freezing in the preferred and normalized step
      length conditions after adjusting for step length and disease severity.
      Coordination of walking worsened in all groups at the shorter normalized step
      lengths with no difference between PD groups in the 25% condition where the
      frequency of freezing was highest. Asymmetry and coordination of gait were not
      predictive of freezing in the 25% condition. CONCLUSIONS: These results suggest
      asymmetry and decreased coordination of gait are affected by step length and may
      not be factors in determining freezing of gait in PD.

PMID- 22397818
TI  - Barriers and bridges to infection prevention and control: results of a
      qualitative case study of a Netherlands' surgical unit.
AB  - OBJECTIVES: The objectives of the study are to observe the overall work
      environment including infection prevention and control (IP&C) practices on the
      target surgical unit; to analyse the policies and procedures in the hospital and
      unit environments; to analyse the barriers and bridges to IP&C that practitioners
      identify in visual narratives of their unit environment and to collect monthly
      specific IP&C-related anonymised data. DESIGN: In this qualitative case study
      analysis, a socio-ecological approach on health systems informed the research
      design and provided a framework to better understand the complexity of
      implementing effective IP&C. SETTING: The study was conducted on a surgical unit
      at a Netherlands' hospital that reported successful reductions in the prevalence
      of targeted multidrug-resistant organisms. METHODS: Research methods included
      unit observations (n=3), review of relevant policies and procedures, five
      practitioner-led photo walkabouts of the unit (n=7), three photo elicitation
      focus groups with practitioners (n=13) and the review of related IP&C data.
      RESULTS: The findings indicate some conditions and processes present that may
      influence the low prevalence of multidrug-resistant organisms, including the
      'search and destroy' active surveillance strategy, low occupancy rates, a
      centralised bed cleaning system and the presence of an active grass roots Hygiene
      in Practice group, which engages practitioners in several ongoing activities to
      promote IP&C on the units. CONCLUSIONS: Further research on the benefits of
      practitioner-led community of practices on IP&C practices such as the Hygiene in
      Practice group is also recommended. Additional case studies to compare theses
      practices with other acute care hospital around the world would be a valuable way
      to better understand what IP&C programmes are most effective in which contexts
      and for what reasons. Further data are available by contacting the primary author
      directly.

PMID- 22397819
TI  - Individuation experience predicts other-race effects in holistic processing for
      both Caucasian and Black participants.
AB  - Same-race (SR) faces are recognized better than other-race (OR) faces, and this
      other-race effect (ORE) is correlated with experience. SR faces are also
      processed more holistically than OR faces, suggesting one possible mechanism for
      poorer performance on OR faces. Studies of object expertise have shown that
      individuating experiences are necessary for holistic processing to develop; yet
      thus far no studies have investigated the role of quality of experience and the
      ORE for holistic processing. In the present study, we found a strong negative
      correlation between a self-report of individuating experience and the ORE in
      holistic processing in both Caucasian and Black participants, indicating that the
      more individuating experience a person has, the less ORE in holistic processing.
      This confirms the critical role of individuating experience in development of
      holistic processing for faces and suggests that quality of experience is a key
      determinant of the manner in which OR faces are processed.

PMID- 22397820
TI  - Dissociating controlled from automatic processing in temporal preparation.
AB  - The aim of the present study was to investigate the controlled versus the
      automatic nature of temporal preparation. If temporal preparation involves
      controlled rather than automatic processing, it should be reduced by the addition
      of a concurrent demanding task. This hypothesis was tested by comparing
      participants' performance in a temporal preparation task that measured two main
      effects of temporal preparation (temporal orienting and sequential effects)
      between a single-task and a dual-task condition. In the single-task condition,
      participants responded to a visual target presented after symbolic cues that were
      highly predictive of the moment of target onset. In the dual-task condition, the
      temporal preparation task was performed concurrently with a working memory task.
      The results showed that sequential effects survived to dual-task interference,
      while temporal orienting was reduced as a function of the competition for
      executive resources required by both working memory and temporal preparation
      tasks. These findings provide direct behavioural evidence that temporal orienting
      and sequential effects involve dissociable cognitive processes.

PMID- 22397821
TI  - Does a 'tight' hamstring predict low back pain reporting during prolonged
      standing?
AB  - The purpose of this study was to investigate the relationship between hamstring
      passive stiffness and extensibility in asymptomatic individuals with the
      reporting of low back pain during 2-h prolonged standing. Twenty healthy
      participants with no history of low back pain (mean+/-SD, age 22.6+/-2.7 years,
      height 1.74+/-0.09 m, weight 76.2+/-14.8 kg). Low back pain (VAS score; mm) was
      continuously monitored during 2-h prolonged standing. Hamstring extensibility,
      passive stiffness, and stretch tolerance were measured before and after prolonged
      standing using an instrumented straight leg raise (iSLR). Ten participants
      reported a clinically relevant increase (Delta VAS>10mm) in low back pain during
      prolonged standing. Hamstring extensiblity (leg degrees (max)), passive stiffness
      (Nm. degrees (-1)), and stretch tolerance (VAS; mm) were no different between
      pain developers and non-pain developers. No changes in hamstring measures were
      observed following 2-h prolonged standing. No relationship was observed in this
      study between measures of hamstring extensibility and the reporting of low back
      pain during prolonged standing. There is no evidence to recommend hamstring
      extensibility interventions (i.e. passive stretching) as a means of reducing pain
      reporting in occupations requiring prolonged standing.

PMID- 22397822
TI  - Immuno-inhibitory PD-L1 can be induced by a peptidoglycan/NOD2 mediated pathway
      in primary monocytic cells and is deficient in Crohn's patients with homozygous
      NOD2 mutations.
AB  - Peptidoglycan (PGN) is a ubiquitous bacterial membrane product that, despite its
      well known pro-inflammatory properties, has also been invoked in immuno-tolerance
      of the gastrointestinal tract. PGN-induced mucosal IL-10 secretion and
      downregulation of Toll like receptors are potential mechanisms of action in the
      gut but there are few data on tolerogenic adaptive immune responses and PGN.
      Here, using blood-derived mononuclear cells, we showed that PGN induced marked
      cell surface expression of PD-L1 but not PD-L2 or CD80/CD86, and specifically in
      the CD14(+) monocytic fraction. This was reproduced at the gene level with rapid
      induction (<4 h) and, unlike for LPS stimulation, was still sustained at 24 h.
      Using transfected and native muramyl dipeptide (MDP), which is a cleavage product
      of PGN and a specific NOD2 agonist, in assays with wild type cells or those from
      patients with Crohn's disease carrying the Leu1007 frameshift mutation of NOD2,
      we showed that (i) both NOD2 dependent and independent signalling (appearing TLR2
      mediated) occurred for PGN upregulation of PD-L1 (ii) upregulation is lost in
      response to MDP in patients with the homozygous mutation and (iii) PD-L1
      upregulation was unaffected in patients with heterozygous mutations as previously
      reported for cytokine responses to MDP. The uptake of PGN and its cleavage
      products by the intestinal mucosa is well recognised and further work should
      consider PD-L1 upregulation as one potential mechanism of the commensal flora
      driven intestinal immuno-tolerance. Indeed, recent work has shown that loss of PD
      L1 signalling in the gut breaks CD8(+) T cell tolerance to self antigen and leads
      to severe autoimmune enteritis.

PMID- 22397823
TI  - Continuous microalgae recovery using electrolysis with polarity exchange.
AB  - There is increasing interest in the use of microalgae as a renewable source for
      the production of fuels and chemicals, but improvements are needed in all steps
      of this process, including harvesting. A continuous microalgae harvest system was
      developed based on electrolysis, referred to here as a continuous electrolytic
      microalgae (CEM) harvest system. This innovative system combines cultivation and
      harvesting and enables continuous and efficient concentration of microalgae. The
      electrodes were subject to a polarity exchange (PE) in the middle of the
      operation to further improve the harvest efficiency. Use of PE, rather than
      conventional electro-coagulation-flotation (ECF), led to more efficient cell
      recovery and more uniform recovery over the entire harvest chamber. In addition,
      PE increased the cell growth rate and the circulated cells remained intact after
      harvesting.

PMID- 22397824
TI  - Optimization of an integrated sponge--granular activated carbon fluidized bed
      bioreactor as pretreatment to microfiltration in wastewater reuse.
AB  - A specific integrated fluidized bed bioreactor (iFBBR) was optimized in terms of
      organic loading rate (OLR), hydraulic retention time (HRT) and frequency of new
      sustainable flocculant (NSBF) addition for primary treated sewage effluent (PTSE)
      treatment. It was observed that iFBBR achieved the best performance with the
      operating conditions of 4 times/day NSBF addition, HRT of 90 min and OLR of 8.64
      kg COD/day m(3). The removal efficiencies were found to be more than 93% of
      dissolved organic carbon (DOC), 61% of total nitrogen (T-N) and 60% of total
      phosphorus (T-P). iFBBR as pretreatment of submerged microfiltration (SMF) is
      successful in increasing the critical flux and reducing the membrane fouling.
      NSBF-iFBBR-SMF hybrid system led to very high organic removal efficiency with an
      average DOC removal of 97% from synthetic PTSE.

PMID- 22397825
TI  - Preparation of activated carbon from edible fungi residue by microwave assisted
      K2CO3 activation--application in reactive black 5 adsorption from aqueous
      solution.
AB  - Preparation of activated carbon from the edible fungi residue (EFR) by microwave
      assisted K(2)CO(3) activation was studied. The optimum preparation conditions
      were as follows: radiation time of 16 min, K(2)CO(3)/EFR ratio of 0.8 and
      microwave power of 520 W. The iodine number, the amount of methylene blue
      adsorption and the yield of activated carbon prepared under optimum conditions
      were 732.74, 172.43 mg/g and 23.0%, respectively. The activated carbon was
      characterized by SEM, FT-IR, N(2) adsorption and pH(ZPC), and then they were used
      as adsorbent for removing reactive black 5 from aqueous solution. The highest
      removal efficiency of 100% could be achieved at the solution pH of 2.0, the
      adsorption efficiency descended with the increasing of pH and the optimum
      activated carbon dose was 8.75 g/L. The Langmuir isotherm well fit the adsorption
      process with the complete monolayer adsorption capacity of 19.6 mg/g and the
      equilibrium adsorption constant of 0.39 L/mg.

PMID- 22397826
TI  - Abdominal hemangiomas: a pictorial review of unusual, atypical, and rare types.
AB  - Hemangiomas are a radiologist's dream lesions because they allow a confident
      diagnosis most of the time. However, within the abdomen, hemangiomas may occur in
      such atypical locations and can have such unusual features that they cause
      significant diagnostic dilemma and may end up being excised surgically. The
      literature is replete with isolated case reports of atypical hemangiomas in the
      abdominal cavity, and, to our knowledge, so far, there is no comprehensive
      review. We present, in this article, a pictorial review of a gamut of uncommon
      hemangiomas and hemangiomatosis syndromes. Knowledge of these rare types can help
      in limiting diagnostic errors and increase the confidence of radiologists, thus
      avoiding unnecessary surgeries.

PMID- 22397827
TI  - Diffusion-weighted imaging in optic neuritis.
AB  - PURPOSE: To evaluate imaging characteristics of optic nerves by using magnetic
      resonance imaging, especially diffusion-weighted imaging (DWI) with apparent
      diffusion coefficient measurements in acute and chronic phases of optic neuritis
      (ON). MATERIALS AND METHODS: A retrospective study was conducted by using records
      of 14 patients with clinically suspected acute ON (15 nerves), 5 chronic ON (7
      nerves), and 11 normal volunteers with no eye symptoms were used as controls.
      Magnetic resonance imaging was performed by a 1.5T scanner. Affected nerves were
      evaluated for sizes, signal characteristics on DWI and T2-weighted imaging
      (T2WI), contrast enhancement, and apparent diffusion coefficient values. Visually
      assessed characteristics were compared between the acute and chronic, whereas
      apparent diffusion coefficient values were assessed among acute ON, chronic ON,
      and the control groups by using the Fisher exact test and Mann-Whitney U test.
      RESULTS: There were significant differences in the diameter of the optic nerves,
      hyperintensity on DWI, and enhancement characteristics on post-enhanced images in
      acute and chronic phases of ON (P = .0001, P < .0001, and P = .0022,
      respectively), apparent diffusion coefficient values of the optic nerves in acute
      ON, chronic ON, and control groups also differed significantly from each other.
      CONCLUSION: In conclusion, DWI can add valuable information in assessment of
      damage to nerve and neuronal barriers and thus in predicting recovery in cases of
      ON.

PMID- 22397828
TI  - The assessment of anemia from attenuation values of cranial venous drainage on
      unenhanced computed tomography of the head.
AB  - OBJECTIVE: To determine if prediction of anemia is possible from quantitative
      analyses of unenhanced cranial computed tomography (CT) images. METHODS: A
      retrospective chart review revealed 101 patients who had hemoglobin and
      hematocrit levels obtained within 24 hours of an unenhanced cranial CT. Regions
      of interest were the place on the torcular Herophili (confluence of sinuses) and
      the left and right transverse sinuses. Attenuation values were correlated with
      hemoglobin and hematocrit to investigate any possible relationship. RESULTS:
      Hemoglobin levels were correlated with torcular and transverse sinus attenuation
      levels. For every 10 Hounsfield unit (HU) increase in torcular attenuation,
      hemoglobin levels increased by 16.3 g/L (P < .001). When subgroup analysis was
      performed, by sex, for every 10 HU increase in torcular attenuation, hemoglobin
      levels increased by 22.6 g/L (P < .001) in men and 8.96 g/L (P < .05) in women.
      CONCLUSION: The attenuation values for venous drainage on unenhanced cranial CT
      constitute a practical adjunct in the assessment of anemia. Given the number of
      individuals undergoing CT without blood work, this rapid assessment technique for
      anemia is a convenient means for narrowing possible diagnoses.

PMID- 22397829
TI  - ?

PMID- 22397830
TI  - The frequency and reasons for vaginal examinations in labour.
AB  - OBJECTIVE: Vaginal examinations (VEs) in labour are a routine part of intrapartum
      care. Current U.K. guidelines recommend that VEs are offered to women at regular
      intervals of not less than 4h and only performed when justifiably necessary.
      However, justification may be interpreted differently by different midwives. This
      study aimed to investigate (i) the number of VEs performed in relation to length
      of labour and (ii) the reasons given by midwives for performing the VE. METHODS:
      This study recruited a group of women (n=144) admitted in either spontaneous
      labour or for induction of labour from one NHS hospital in Scotland. The number
      of VEs performed, the reason provided by the midwife for its need and the length
      of labour were all recorded. FINDINGS: The number of VEs carried out (mean 2.9,
      SD 1.5, range 1-7) increased as length of time in labour in hospital increased.
      Approximately half the sample (52%) had 3 or more VEs during labour. Almost 70%
      of women had more VEs than expected when the criteria of 4 hourly VEs was
      applied. The most common reason given by midwives for performing a VE was to
      assess labour progress and to assess the commencement of labour. CONCLUSIONS:
      Despite maternity care policy to limit interventions in normal labour, we found
      that a substantial number of women received more VEs than was consistent with
      adherence to guidelines. However, until further research is conducted to validate
      other measures of labour progress, the number of VEs undertaken during labour is
      unlikely to decrease.

PMID- 22397831
TI  - Response of antioxidant activity and sensory quality in fresh-cut pear as
      affected by high O(2) active packaging in comparison with low O(2) packaging.
AB  - Effects of active modified atmosphere packaging (initial O(2)/CO(2): 5/5; 30/5;
      and 80/0) and passive packaging [initial O(2)/CO(2): 20.8/0 (air)] on the
      antioxidant capacity and sensory quality of fresh-cut 'Yaoshan' pear stored at 4 
      degrees C for 12 days were investigated. Samples stored in high O(2) (30% and
      80%) packages had higher phenolics and anthocyanin contents compared with those
      in passive and low O(2) packages. After 12 days of storage, phenolics and
      anthocyanin contents of 80% O(2) samples were 2.5 and 12 times, respectively,
      higher than those in the passive package and 3 and 2 times higher than those in
      low O(2) package. High O(2) modified atmosphere packaging was effective in
      keeping free radical scavenging capacity as measured by the DPPH assay. The
      sensory evaluation indicated that surface color of cut fruits were stable for at
      least 12 days in the high O(2) modified atmosphere packaging. The results
      suggested that high O(2) modified atmosphere packaging could be used to inhibit
      browning and prolong the shelf life of fresh-cut 'Yaoshan' pears in spite of more
      than 50% loss in vitamin C content.

PMID- 22397832
TI  - Pemetrexed-induced skin sclerosis.

PMID- 22397833
TI  - Effects of a 2-year healthy eating and physical activity intervention for 3-6
      year-olds in communities of high and low socio-economic status: the POP
      (Prevention of Overweight among Pre-school and school children) project.
AB  - OBJECTIVE: The purpose of the present study was to evaluate the effects of a
      school-based, 2-year, multi-component intervention on BMI, eating and physical
      activity behaviour in Flanders, Belgium, targeting children aged 3-6 years in
      communities of high and low socio-economic status (SES). DESIGN: Cluster
      randomized controlled trial. SETTING: Thirty-one pre-primary and primary schools
      in three different intervention communities and three paired-matched (on SES
      profile) control communities in Flanders, Belgium. SUBJECTS: BMI Z-scores at
      baseline and follow-up were calculated for 1102 children. Questionnaires with
      sociodemographic data and FFQ were available from 694 of these 1102 children.
      RESULTS: No significant effects were found on BMI Z-scores for the total sample.
      However, there was a significant decrease in BMI Z-score of 0.11 in the low-SES
      intervention community compared with the low-SES control community, where the BMI
      Z-score increased by 0.04 (F = 6.26, P = 0.01). No significant intervention
      effects could be found for eating behaviour, physical activity or screen-time.
      There were no significant interaction effects of age and gender of the children
      on the outcome variables. CONCLUSIONS: Although no significant effects were found
      for BMI Z-scores in the total sample, this intervention had a promising effect in
      the low-SES community of reducing excess weight gain among young children.

PMID- 22397834
TI  - Characterizing the geometry of InAs nanowires using mirror electron microscopy.
AB  - Mirror electron microscopy (MEM) imaging of InAs nanowires is a non-destructive
      electron microscopy technique where the electrons are reflected via an applied
      electric field before they reach the specimen surface. However strong caustic
      features are observed that can be non-intuitive and difficult to relate to
      nanowire geometry and composition. Utilizing caustic imaging theory we can
      understand and interpret MEM image contrast, relating caustic image features to
      the properties and parameters of the nanowire. This is applied to obtain
      quantitative information, including the nanowire width via a through-focus series
      of MEM images.

PMID- 22397835
TI  - Toxic effects of 50 Hz electromagnetic field on memory consolidation in male and
      female mice.
AB  - In this study, the effect of exposure to an 8 mT, 50 Hz extremely low-frequency
      electromagnetic field (ELF EMF) on memory consolidation of adult male and female
      mice was studied. For this purpose male and female mice were randomly distributed
      among six groups (n = 10 in each group). Using passive avoidance task, despite
      its natural tendency, mouse learns to stay on a small platform to avoidant
      electric shock. Immediately after the learning session, laboratory animals in the
      experimental groups were placed in an 8 mT, 50 Hz sinusoidal EMF for 4 h. The
      second male and female groups were sham exposed (exposure device off) and the
      third groups were considered as the controls. Twenty-four hours after the
      learning session, the animals were placed on small platform again and step-down
      latency was measured as the memory consolidation index. Significant (p < 0.05)
      decreases were determined among groups in memory function and results showed that
      exposure to an 8 mT, 50 Hz EMF for 4 h has devastating effects on memory
      consolidation in male and female mice.

PMID- 22397836
TI  - Reducing the inhibitory effect of cigarette smoke on the activity of oral
      peroxidase by the addition of berberine in cigarette filter.
AB  - This study was carried out to evaluate the effect of cigarette smoke (CS) on the
      activity of oral peroxidase (OPO) after berberine was added to the cigarette
      filter. Activated carbon fiber (ACF) was chosen to load berberine as a part of
      the cellulose acetate (CA) filter to obtain the modified B-ACF cigarette filter.
      Then the effects of CS from the testing cigarettes on the activity of OPO were
      investigated in vitro by the 2-nitrobenzoic acid assay, and the smoke chemistry
      was also analyzed, especially the content of hydrogen cyanide (HCN) in the CS.
      The results indicated that the loss of activity of OPO in B-ACF filter cigarette
      group decreased by 20% and 25%, compared with those of ACF and CA filter
      cigarette groups, respectively. The relative residual activity of OPO in B-ACF
      filter group was increased with the increase of berberine in the filter compared
      with the CA filter group. It could be observed that the reduction in HCN might be
      related to the berberine in the cigarette filter, reducing the inhibition of CS
      on the activity of OPO.

PMID- 22397837
TI  - Influence of sugar type on the bioavailability of cocoa flavanols.
AB  - The beneficial effects of cocoa on vascular function are mediated by the
      absorption of monomeric flavanols into the circulation from the small intestine.
      As such, an understanding of the impact of the food matrix on the delivery of
      flavanols to the circulation is critical in assessing the potential vascular
      impact of a food. In the present study, we investigated the impact of
      carbohydrate type on flavanol absorption and metabolism from chocolate. A
      randomised, double-blind, three-arm cross-over study was conducted, where fifteen
      volunteers were randomly assigned to either a high-flavanol (266 mg) chocolate
      containing maltitol, a high-flavanol (251 mg) chocolate with sucrose or a low
      flavanol (48 mg) chocolate with sucrose. Test chocolates were matched for micro-
      and macronutrients, including the alkaloids theobromine and caffeine, and were
      similar in taste and appearance. Total flavanol absorption was lower after
      consumption of the maltitol-containing test chocolate compared with following
      consumption of its sucrose-containing equivalent (P = 0.002). Although the O
      methylation pattern observed for absorbed flavanols was unaffected by sugar type,
      individual levels of unmethylated ( - )-epicatechin metabolites, 3'-O-methyl
      epicatechin and 4'-O-methyl-epicatechin metabolites were lower for the maltitol
      containing test chocolate compared with the sucrose-containing equivalent.
      Despite a reduction in the total plasma pool of flavanols, the maximum time (T
      max) was unaffected. The present data indicate that full assessment of
      intervention treatments is vital in future intervention trials with flavanols and
      that carbohydrate content is an important determinant for the optimal delivery of
      flavanols to the circulation.

PMID- 22397838
TI  - Biomineralization-based conversion of carbon dioxide to calcium carbonate using
      recombinant carbonic anhydrase.
AB  - Recently, as a mimic of the natural biomineralization process, the use of
      carbonic anhydrase (CA), which is an enzyme catalyzing fast reversible hydration
      of carbon dioxide to bicarbonate, has been suggested for biological conversion of
      CO(2) to valuable chemicals. While purified bovine CA (BCA) has been used in
      previous studies, its practical utilization in CO(2) conversion has been limited
      due to the expense of BCA preparation. In the present work, we investigated
      conversion of CO(2) into calcium carbonate as a target carbonate mineral by using
      a more economical, recombinant CA. To our knowledge, this is the first report of
      the usage of recombinant CA for biological CO(2) conversion. Recombinant alpha
      type CA originating in Neisseria gonorrhoeae (NCA) was highly expressed as a
      soluble form in Escherichia coli. We found that purified recombinant NCA which
      showed comparable CO(2) hydration activity to commercial BCA significantly
      promoted formation of solid CaCO(3) through the acceleration of CO(2) hydration
      rate, which is naturally slow. In addition, the rate of calcite crystal formation
      was also accelerated using recombinant NCA. Moreover, non-purified crude
      recombinant NCA also showed relatively significant ability. Therefore,
      recombinant CA could be an effective, economical biocatalyst in practical CO(2)
      conversion system.

PMID- 22397839
TI  - Assessment of bacterial communities and characterization of lead-resistant
      bacteria in the rhizosphere soils of metal-tolerant Chenopodium ambrosioides
      grown on lead-zinc mine tailings.
AB  - Bacterial communities in the rhizosphere soils of metal tolerant and accumulating
      Chenopodium ambrosioides grown in highly and moderately lead-zinc mine tailings
      contaminated-soils as well as the adjacent soils with low metal contamination
      were characterized by using cultivation-independent and cultivation techniques. A
      total of 69, 73, and 83 bacterial operational taxonomic units (OTUs) having 84.8
      100% similarity with the closest match in the database were detected among high,
      moderate, and low-contamination soil clone libraries, respectively. These OTUs
      had a Shannon diversity index value in the range of 4.06-4.30. There were 9, 10,
      and 14 bacterial genera specific to high, moderate, and low metal-contaminated
      soil clone libraries, respectively. Phylogenetic analysis showed that the Pb
      resistant isolates belonged to 8 genera. Pseudomonas and Arthrobacter were
      predominant among the isolates. Most of the isolates (82-86%) produced indole
      acetic acid and siderophores. More strains from the highly metal-contaminated
      soil produced 1-aminocyclopropane-1-carboxylate deaminase than the strains from
      the moderately and lowly metal-contaminated soils. In experiments involving
      canola grown in quartz sand containing 200 mg kg(-1) of Pb, inoculation with the
      isolated Paenibacillus jamilae HTb8 and Pseudomonas sp. GTa5 was found to
      significantly increase the above-ground tissues dry weight (ranging from 19% to
      36%) and Pb uptake (ranging from 30% to 40%) compared to the uninoculated
      control. These results show that C. ambrosioides harbor different metal-resistant
      bacterial communities in their rhizosphere soils and the isolates expressing
      plant growth promoting traits may be exploited for improving the phytoextraction
      efficiency of Pb-polluted environment.

PMID- 22397840
TI  - Effects of a catalytic converter on PCDD/F, chlorophenol and PAH emissions in
      residential wood combustion.
AB  - Catalytic converters can be used to decrease carbon monoxide, organic compounds
      and soot from small-scale wood-fired appliances. The reduction is based on the
      oxidation of gaseous and particulate pollutants promoted by catalytic transition
      metal surfaces. However, many transition metals have also strong catalytic effect
      on PCDD/F formation. In this study birch logs were burned in a wood-fired stove
      (18 kW) with and without a catalytic converter with palladium and platinum as
      catalysts. PCDD/F, chlorophenol and PAH concentrations were analyzed from three
      phases of combustion (ignition, pyrolysis and burnout) and from the whole
      combustion cycle. PCDD/F emissions without the catalytic converter were at a
      level previously measured for wood combustion (0.15-0.74 ng N m(-3)). PAH
      emissions without the catalytic converter were high (47-85 mg N m(-3)) which is
      typical for batch combustion of wood logs. Total PAH concentrations were lower
      (on average 0.8-fold), and chlorophenol and PCDD/F levels were substantially
      higher (4.3-fold and 8.7-fold, respectively) when the catalytic converter was
      used. Increase in the chlorophenol and PCDD/F concentrations was most likely due
      to the catalytic effect of the platinum and palladium. Platinum and palladium may
      catalyze chlorination of PCDD/Fs via the Deacon reaction or an oxidation process.
      The influence of emissions from wood combustion to human health and the
      environment is a sum of effects caused by different compounds formed in the
      combustion. Therefore, the usage of platinum and palladium based catalytic
      converters to reduce emissions from residential wood combustion should be
      critically evaluated before wide-range utilization of the technology.

PMID- 22397841
TI  - Palmaris profundus tendon prohibiting endoscopic carpal tunnel release: case
      report.
AB  - Palmaris profundus is an aberrant muscle of forearm and wrist anatomy. It has no
      discernible function, but its tendon has been implicated as a cause of carpal
      tunnel syndrome. Previously, all cases of palmaris profundus in the literature
      have been encountered during either open surgery or cadaveric dissection. We
      report a case of palmaris profundus encountered during attempted single-portal
      endoscopic carpal tunnel release, necessitating conversion to an open approach.
      There was a unique point of tendon insertion onto the undersurface of the
      transverse carpal ligament, more proximal than what has been previously described
      in the literature. There were other anomalies present as well, including a
      persistent median artery and bifid median nerve. Given the volar position of the
      structure, its proximal point of insertion, and its minimal bulk, we did not feel
      that this was the cause of our patient's carpal tunnel syndrome.

PMID- 22397842
TI  - Metacarpal hypoplasia associated with congenital constriction band syndrome.
AB  - PURPOSE: The amputation of digits that occurs in association with congenital
      constriction band syndrome (CCBS) is often described as similar to that resulting
      from trauma. Some previous studies have suggested that no bone hypoplasia is
      present in the affected limb proximal to the amputated part. The purpose of this
      study was to report our series of patients with metacarpal hypoplasia in
      amputated digits associated with CCBS. METHODS: We reviewed a total of 37 hands
      of 24 patients diagnosed as having amputated fingers owing to CCBS and evaluated
      the clinical features of the metacarpal bone hypoplasia. RESULTS: We found
      coexistent metacarpal hypoplasia in 11 hands in 9 patients. Three of the patients
      were male and 6 were female. The average age at the time of examination was 9
      years (range, 4-20 y). We observed metacarpal hypoplasia in cases of amputation
      at the level of the proximal phalanx and not at the level of the middle phalanx.
      CONCLUSIONS: We found metacarpal hypoplasia in 38% of patients and in 30% of
      hands with amputated digits owing to CCBS. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Prognostic IV.

PMID- 22397843
TI  - The mechanism of ulnar-sided perilunate instability of the wrist: a cadaveric
      study and 6 clinical cases.
AB  - PURPOSE: To define the mechanism of ulnar-sided perilunate instability using a
      cadaveric model and correlate these biomechanical findings with 6 clinical cases.
      METHODS: We mounted 16 fresh-frozen human cadaver arms and loaded them to failure
      in extension and radial deviation, recreating our understanding of the injury
      mechanism leading to ulnar-sided perilunate instability of the wrist. After
      testing, we examined the wrists clinically and radiographically. We identified,
      examined, and treated 6 patients with ulnar-sided perilunate instability over a
      period of 5 years. Based on these data, we propose a 3-stage mechanism for ulnar
      sided perilunate instability of the wrist. RESULTS: In 13 of 16 specimens, we
      observed failure of ulnotriquetral, ulnolunate, and ulnocapitate ligaments as
      well as the dorsal scaphotriquetral and dorsal radiotriquetral ligaments. In 11
      of these 13, the lunotriquetral interosseous ligament was disrupted, and in 2 of
      the 11, a dorsal perilunate dislocation occurred. After comparing these
      laboratory findings with clinical findings in 6 patients with ulnar-sided
      perilunate instability, we propose the following 3-stage mechanism for ulnar
      sided perilunate instability: stage 1, disruption of the lunotriquetral
      interosseous ligament; stage 2, stage 1 plus disruption of the ulnolunate,
      ulnotriquetral, and ulnocapitate ligaments as well as the dorsal scaphotriquetral
      and radiotriquetral ligaments; and stage 3, stage 2 with progression of the
      injury through the midcarpal joint plus disruption of the scapholunate and
      radioscapholunate ligaments, potentially resulting in a dorsal perilunate
      dislocation. CONCLUSIONS: We describe a 3-stage mechanism of ulnar-sided
      perilunate ligamentous wrist injury that can lead to dorsal perilunate
      dislocation. We recommend considering ulnar-sided perilunate instability of the
      wrist in patients with ulnar wrist pain after a fall on the outstretched wrist.
      CLINICAL RELEVANCE: Ulnar-sided wrist injury can lead to subtle forms of
      perilunate instability.

PMID- 22397844
TI  - Salvage of complete degloved digits with reversed vascularized pedicled forearm
      flap: a new technique.
AB  - Complete ring avulsion injury necessitates a difficult choice between
      microvascular repair and revision amputation. Microvascular repair is technically
      difficult and amputation may leave an unsatisfactory result. We describe an
      alternative method whereby a reverse radial forearm flap is wrapped around the
      complete degloved digit. This provides good quality cover to the whole volar,
      dorsum, and both sides of the finger. We performed 26 pedicle radial forearm
      flaps for 26 patients in the Hand and Reconstructive Microsurgery Unit, Sohag
      University Hospital, from 2001 to 2009. Indications included soft tissue coverage
      of the thumb (n = 8), ring finger (n = 11), index finger (n = 4), middle finger
      (n = 2), and little finger (n = 1). Finger salvage was successful in 96% of
      patients. There was complete loss of 1 flap and partial flap loss of a second.
      Finger range of motion was excellent in 18 fingers, good in 7, and fair in 1. Two
      donor sites were closed primarily; the rest were closed with split-thickness skin
      grafts. There were no reports of cold intolerance of the hand or dysesthesias in
      the superficial radial nerve or lateral antebrachial nerve distribution.

PMID- 22397845
TI  - Comparison of 2 forearm reconstructions for longitudinal radioulnar dissociation:
      a cadaver study.
AB  - PURPOSE: We present the results of a cadaveric study of 2 forearm reconstructions
      with radial head replacement for longitudinal radioulnar dissociation injuries.
      METHODS: We created a simulated longitudinal radioulnar dissociation injury in 8
      cadaver forearms. Two reconstructions were performed alternately on each arm:
      patellar tendon interosseous ligament complex reconstruction and the Herbert
      sling extensor retinaculum plication. We performed mechanical testing in a
      materials testing machine with and without a radial head replacement, and
      measured ulnocarpal impaction force through 2 distal ulna strain gauges. We
      determined relative radioulnar displacement using live fluoroscopic analysis of
      implanted stainless-steel beads. RESULTS: Relative radioulnar longitudinal
      displacement in the destabilized forearms was 10.7 compared with 0.7 mm before
      creating the injury. A prosthetic radial head replacement alone decreased the
      displacement by 75% to 2.7 mm. Interosseous ligament reconstruction alone reduced
      the displacement to 5.1 mm and to 1.3 mm when combined with a radial head
      implant. The Herbert sling alone did not improve longitudinal stability. The
      distal ulna force in the native arm was 17 N, or 17% of the force across the
      wrist. The interosseous ligament reconstruction restored the force to 21 N,
      whereas the Herbert sling only marginally decreased the ulna impaction force to
      45 N. Adding a radial head decreased the distal ulna force to 7 N for the
      patellar tendon interosseous ligament reconstruction, and 2 N for the Herbert
      sling. CONCLUSIONS: In longitudinal radioulnar dissociation injuries, the radial
      head is an important stabilizer and should be repaired or replaced to minimize
      radial shortening and ulnar impaction force. Patellar tendon interosseous
      ligament reconstruction effectively restores the ulnocarpal force distribution
      and markedly reduces longitudinal instability at the distal radioulnar joint.
      Combined with radial head arthroplasty, the construct has stability similar to an
      intact forearm. The Herbert sling did not improve longitudinal stability in this
      testing construct. CLINICAL RELEVANCE: Treatment of longitudinal radioulnar
      dissociation may benefit from radial head replacement and interosseous ligament
      reconstruction using a patellar tendon graft.

PMID- 22397846
TI  - Radiographic arthrosis after elbow trauma: interobserver reliability.
AB  - PURPOSE: This study measured observer variation in radiographic rating of elbow
      arthrosis. METHODS: Thirty-seven independent orthopedic surgeons graded the
      extent of elbow arthrosis in 20 consecutive sets of plain radiographs, according
      to the Broberg and Morrey rating system (grade 0, normal joint; grade 1, slight
      joint-space narrowing with minimum osteophyte formation; grade 2, moderate joint
      space narrowing with moderate osteophyte formation; and grade 3, severe
      degenerative change with gross destruction of the joint). The kappa multirater
      measure (kappa) was used to estimate reliability between observers, with 0
      indicating no agreement above chance, and 1 indicating perfect agreement.
      RESULTS: There was fair agreement in arthrosis ratings between surgeons. Surgeons
      with more than 10 years of experience had greater agreement than did surgeons
      with less experience, and surgeons who treated more than 10 elbow fractures per
      year had better agreement than did those treating fewer fractures. In post hoc
      analyses, 2 simplified binary rating systems (eg, "none or mild" vs "moderate or
      severe" arthrosis) resulted in moderate agreement among observers. CONCLUSIONS:
      The 4 grades of the Broberg and Morrey classification system have only fair
      interobserver reliability that is influenced by subspecialty and experience.
      Binary rating systems might be more reliable. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Diagnostic III.

PMID- 22397847
TI  - Both immediate and delayed intracavernous injection of autologous adipose-derived
      stromal vascular fraction enhances recovery of erectile function in a rat model
      of cavernous nerve injury.
AB  - BACKGROUND: Intracavernous injection of cultured adipose-derived stem cells
      (ADSCs) effectively restores erectile function in cavernous nerve (CN)-injured
      rats when administered at the time of injury. However, culturing exposes ADSCs to
      the risk of contamination and dedifferentiation. OBJECTIVE: Explore the effect of
      uncultured autologous adipose-derived stromal vascular fraction (SVF) on
      improving erectile function in a rat model of CN injury when administered at the
      time of injury or 4 wk after injury. DESIGN, SETTING, AND PARTICIPANTS: Eighty
      nine male Sprague Dawley rats were randomly divided into four groups. CN injury
      or sham surgery was performed at the start of the study, and rats were treated
      with either SVF or vehicle. Functional testing and histologic analysis were
      performed 12 wk after CN crush or sham surgery. INTERVENTION: We used
      intracavernous injection of saline immediately after CN crush (n=23),
      intracavernous injection of SVF immediately after CN crush (n=17), intracavernous
      injection of SVF 4 wk after CN crush (n=23), or sham surgery (n=26). OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: We studied intracavernous pressure (ICP)
      response to CN electrostimulation and performed histologic examination of
      midpenile cross-sections. Data were analyzed using one-way analysis of variance
      followed by the Tukey-Kramer test. RESULTS AND LIMITATIONS: Both immediate and
      delayed treatment with SVF resulted in a significantly increased ICP-to-mean
      arterial pressure ratio compared with the vehicle-treated group. Both immediate
      and delayed treatment with SVF significantly increased expression of neuronal
      nitric oxide synthase and neurofilament in dorsal penile nerves compared to the
      vehicle group. Furthermore, the smooth muscle-to-collagen ratio within the corpus
      cavernosum was significantly improved in both of the SVF groups compared to
      vehicle-treated rats. The main limitation of the study is the lack of
      determination of the SVF components. CONCLUSIONS: Uncultured autologous SVF
      injected immediately or 4 wk after CN crush improved erectile function, promoted
      nerve regeneration, and prevented fibrosis of the corpus cavernosum following CN
      injury.

PMID- 22397848
TI  - Monotherapy with alpha-blocker or phosphodiesterase 5 inhibitor for lower urinary
      tract symptoms?

PMID- 22397850
TI  - Are new technologies for detection and treatment of non-muscle-invasive bladder
      cancer (NMIBC) so important? A plea for adoption by teaching programs to improve
      results after standard white light transurethral resection of NMIBC.

PMID- 22397851
TI  - Anticholinergic drugs for adult neurogenic detrusor overactivity: a systematic
      review and meta-analysis.
AB  - CONTEXT: There is a lack of evidence about the efficacy and safety of
      anticholinergic drugs and about the optimal anticholinergic drug, if any, for the
      treatment of adult neurogenic detrusor overactivity (NDO). OBJECTIVE: Review the
      current evidence on the efficacy, safety, and tolerability of anticholinergic
      drugs in the treatment of adult NDO. EVIDENCE ACQUISITION: A literature search
      was conducted from 1966 to May 2011. Meta-analysis of all published randomised
      controlled trials (RCTs) comparing anticholinergic drugs with placebo and
      comparing different types, doses, and routes of administration of anticholinergic
      drugs, in adults with NDO, was performed in accordance with the Preferred
      Reporting Items for Systematic Reviews and Meta-analysis statement. The primary
      outcome was patient-reported cure/improvement of overactive bladder symptoms.
      Secondary outcomes were quality of life (QoL) changes, bladder diary events,
      urodynamic outcomes, adverse events, and costs to health services. EVIDENCE
      SYNTHESIS: A total of 960 patients from 16 RCTs with mean follow-up of 3.8 wk
      were included. Anticholinergic drugs were associated with statistically
      significantly better patient-reported cure/improvement (risk ratio: 2.80; 95%
      confidence interval [CI], 1.64 to 4.77), higher maximum cystometric capacity
      (weighted mean difference [WMD]: 49.49; 95% CI, 15.38 to 84.20), higher volume at
      first contraction (WMD: 49.92; 95% CI, 20.06 to 79.78), and lower maximum
      detrusor pressure (WMD: -38.30; 95% CI, -53.17 to -23.43) when compared with
      placebo. The dry-mouth rates were statistically significantly higher with
      anticholinergics, with no difference in withdrawals because of adverse events.
      There was no statistically significant difference in any of the outcomes between
      oxybutynin and other anticholinergics or among different doses and preparations
      of anticholinergic drugs. No study reported QoL changes or costs to health
      services. CONCLUSIONS: Compared with placebo, anticholinergic treatment in
      patients with NDO is associated with better patient-reported cure/improvement and
      significant reduction of maximum detrusor pressure; however, there is a higher
      incidence of adverse events. None of the anticholinergic drugs or different
      dosages assessed in this review was superior to another.

PMID- 22397852
TI  - Metabolism of a G protein-coupled receptor modulator, including two major 1,2,4
      oxadiazole ring-opened metabolites and a rearranged cysteine-piperazine adduct.
AB  - Metabolites of a G protein-coupled receptor modulator containing 1,2,4-oxadiazole
      and piperazine substructures were identified in vitro in human, rat, and dog
      hepatocyte incubates and in vivo in rat plasma, bile, urine, and feces by using
      14C-radiolabeled parent compound. Exposure coverage for the major circulating
      metabolites in humans at steady state and in preclinical species used in drug
      safety assessments was determined by using pooled plasma samples collected from a
      human multiple ascending dose study and a 3-month rat toxicokinetic study.
      Metabolites M1 and M2, which were formed by opening of the 1,2,4-oxadiazole ring,
      were observed as major metabolites both in vitro and in vivo across species. The
      carboxylic acid metabolite M2 was presumably formed through reductive N-O bond
      cleavage of the oxadiazole ring and subsequent hydrolysis. However, the mechanism
      for the formation of the unusual N-cyanoamide metabolite M1 remains uncertain.
      Neither M1 nor M2 had any target activity, as did parent drug P. In rat bile,
      rearranged Cys-piperazine and Gly-Cys-piperazine adducts, involving the formation
      of a five-membered heteroaromatic imidazole derivative from a six-membered
      piperazine ring, were observed as minor metabolites. These findings support a
      previously reported mechanism regarding glutathione detoxification for piperazine
      bioactivation products.

PMID- 22397854
TI  - Adequacy of family foods for complementary feeding.

PMID- 22397855
TI  - Coffee consumption and risk of chronic diseases: changing our views.

PMID- 22397853
TI  - Generation and characterization of a CYP2A13/2B6/2F1-transgenic mouse model.
AB  - CYP2A13, CYP2B6, and CYP2F1, which are encoded by neighboring cytochrome P450
      genes on human chromosome 19, are active in the metabolic activation of many
      drugs, respiratory toxicants, and chemical carcinogens. To facilitate studies on
      the regulation and function of these human genes, we have generated a
      CYP2A13/2B6/2F1-transgenic (TG) mouse model (all *1 alleles). Homozygous
      transgenic mice are normal with respect to gross morphological features,
      development, and fertility. The tissue distribution of transgenic mRNA expression
      agreed well with the known respiratory tract-selective expression of CYP2A13 and
      CYP2F1 and hepatic expression of CYP2B6 in humans. CYP2A13 protein was detected
      through immunoblot analyses in the nasal mucosa (NM) (~100 pmol/mg of microsomal
      protein; similar to the level of mouse CYP2A5) and the lung (~0.2 pmol/mg of
      microsomal protein) but not in the liver of the TG mice. CYP2F1 protein, which
      could not be separated from mouse CYP2F2 in immunoblot analyses, was readily
      detected in the NM and lung but not the liver of TG/Cyp2f2-null mice, at levels
      10- and 40-fold, respectively, lower than that of mouse CYP2F2 in the TG mice.
      CYP2B6 protein was detected in the liver (~0.2 pmol/mg of microsomal protein) but
      not the NM or lung (with a detection limit of 0.04 pmol/mg of microsomal protein)
      of the TG mice. At least one transgenic protein (CYP2A13) seems to be active,
      because the NM of the TG mice had greater in vitro and in vivo activities in
      bioactivation of a CYP2A13 substrate, 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (a lung carcinogen), than did the NM of wild-type mice.

PMID- 22397856
TI  - Unplanned admission to the intensive care unit after total hip arthroplasty.
AB  - Triage to the intensive care unit (ICU) after elective total hip arthroplasty
      proves a complex medical and resource decision point. A total of 1259 consecutive
      total hip arthroplasties were reviewed; 89 patients experienced unplanned ICU
      admissions. Significant risk factors for ICU admission in univariate analysis
      were age greater than 75 years, revision surgery, obstructive sleep apnea,
      creatinine clearance less than 60 mL/min, prior myocardial infarction, American
      Society of Anesthesiologist class 3 or greater, use of vasopressors
      intraoperatively, and body mass index greater than 35 kg/m(2). With multiple
      regression, age greater than 75 years (odds ratio [OR], 2.6 [1.2-5.6]), revision
      surgery (OR, 5.8 [3.0-11.4]), creatinine clearance less than 60 mL/min (OR, 6.5
      [2.5-16.3]), prior myocardial infarction (OR, 7.2 [2.0-25.4]), and body mass
      index greater than 35 kg/m(2) (OR, 2.9 [1.4-6.2]) were predictive of unplanned
      ICU admission. With 1 risk factor, the risk of ICU admission was 40%, 2 (75%), 3
      (93.5%), 4 (98.5%), and 5 (>99%). A prospective study of these risk factors is
      needed to establish a threshold for planned ICU admission.

PMID- 22397857
TI  - A minimum of 10-year follow-up of the Burch-Schneider cage and bulk allografts
      for the revision of pelvic discontinuity.
AB  - Eighteen consecutive hips with pelvic discontinuity and associated periprosthetic
      bone deficiency were treated with bulk allografts and Burch-Schneider
      antiprotrusio cage. Clinical and radiographic follow-up was performed at an
      average of 13.5 (range, 10.5-16.6) years. Three cages required re-revision
      because of infection (1) and aseptic loosening (2). Average Harris hip score
      improved from 31.9 to 77.0 points (P < .001). A severe resorption of the bone
      graft occurred in 2 hips. The stability of the cage was detected in 13 cases. The
      cumulative survival rate at 16.6 years with acetabular revision for any reason,
      radiographic loosening, or unhealing of the discontinuity as the end point was
      72.2%. The use of Burch-Schneider cage and bulk allografts is an effective
      technique for the treatment of pelvic discontinuity.

PMID- 22397858
TI  - Cutaneous manifestation of metallosis in a metal-on-metal total hip arthroplasty
      after acetabular liner dissociation.
AB  - In this case report, we describe a cutaneous manifestation of extensive
      metallosis in a patient 4 months post-metal-on-metal total hip arthroplasty with
      a Pinnacle cup with dissociation of the liner from the shell and resultant stripe
      burnishing of the shell and notch wear of the femoral neck. Dissociation of a
      metal liner has not been previously reported with this implant. Cutaneous
      metallosis has only been reported once in the literature. Clinicians should
      heighten their suspicion for metallosis secondary to hardware failure when
      encountering patients with skin discoloration in the setting of a painful and
      poorly functioning hip arthroplasty. In patients with failure of a metal-on-metal
      prosthesis with a modular metal liner in the acetabular component, liner
      dissociation must be considered.

PMID- 22397859
TI  - Squeaking in a Delta ceramic-on-ceramic uncemented total hip arthroplasty.
AB  - Squeaking is one of the main concerns related to the use of ceramic-on-ceramic
      total hip arthroplasty. Although it has received much recent publicity, most of
      the previous reports on this complication have been related to the use of the
      second generation of alumina ceramics combined with a cup having an elevated
      metal rim to protect the ceramic liner from neck impingement. We report a patient
      with a third-generation Biolox Delta (CeramTec AG, Plochingen, Germany) ceramic
      on-ceramic uncemented total hip arthroplasty without an elevated metal rim in the
      cup who presented with a squeaking hip at 23 months postoperative. Although this
      complication was mainly related to a specific design in the literature, this case
      demonstrates that newer generation of ceramics can also present squeaking.

PMID- 22397860
TI  - Tibial stem tip pain in stemmed revision total knee arthroplasty: treatment with
      tension band plating.
AB  - The use of stemmed modular components in revision total knee arthroplasty has led
      to increasingly described pain located at the tip of the stem of the implant.
      This has been described in the literature as being due to the elastic modulus
      mismatch between the stem tip and the host bone. Current management is re
      revision total knee arthroplasty in an attempt to alleviate the mismatch. This
      case report describes a novel technique using a dynamic compression plate acting
      as a tension band at the stem tip to successfully treat this condition.

PMID- 22397861
TI  - The persistence of Staphylococcus aureus decolonization after mupirocin and
      topical chlorhexidine: implications for patients requiring multiple or delayed
      procedures.
AB  - Preoperative screening and decolonization of methicillin-sensitive and
      methicillin-resistant Staphylococcus aureus (MSSA and MRSA, respectively) are
      advocated to reduce surgical site infections. We determined the rate and duration
      of decolonization in patients undergoing elective orthopedic surgery. Patients
      undergoing elective orthopedic surgery were seen in our preoperative testing
      program (PAT) and had their anterior nares cultured for MRSA and MSSA. All
      patients were treated with intranasal mupirocin and a topical chlorhexidine
      solution. A cohort of patients returned to PAT before a subsequent elective
      procedure and were recultured. All culture results and time between PAT visits
      were recorded, and the rates of successful initial and persistent decolonization
      were determined. Six hundred ten patients visited PAT 1290 times. Overall, 94
      (70.1%) of 134 patients with initially MRSA- or MSSA-positive cultures remained
      decolonized at a mean time of 156 days (SD=140), whereas 40 patients (29.9%) were
      not decolonized by the time of repeat testing at a mean time of 213 days
      (SD=187). At repeat testing, there were 2 newly MRSA-positive and 35 newly MSSA
      positive patients. Staphylococcus aureus decolonization with intranasal mupirocin
      and topical chlorhexidine was effective but not persistent in a significant
      proportion of patients. A small number of previously uncolonized patients became
      colonized. Staphylococcus aureus screening and decolonization protocols must be
      repeated before any readmission, regardless of prior colonization status.

PMID- 22397862
TI  - Heparin-induced thrombocytopenia after total knee arthroplasty, with subsequent
      adrenal hemorrhage.
AB  - Heparin-induced thrombocytopenia (HIT) is a life-threatening immune-mediated
      adverse effect of chemoprophylaxis for venous thromboembolic events. We present
      the case of a 44-year-old man who developed bilateral adrenal hemorrhage (BAH) as
      a sequela of HIT after bilateral total knee arthroplasty. In our review of
      clinical management of HIT-induced BAH, we discuss the 21 published cases of this
      phenomenon, 14 of which occurred after orthopedic surgery. Given the potentially
      fatal consequences and the importance of early intervention, physicians should be
      on the alert for recognizing HIT-induced BAH in patients experiencing shock
      unresponsive to fluid resuscitation. In addition, chemoprophylaxis with
      alternative agents such as a synthetic pentasaccharide factor Xa inhibitor and
      oral direct thrombin inhibitors that are associated with lower risks of HIT in
      orthopedic patients merits exploration.

PMID- 22397863
TI  - Revisiting the Brewster Angle Microscopy: the relevance of the polar headgroup.
AB  - The Brewster Angle Microscopy (BAM) is a powerful microscopy technique allowing
      the in situ visualization of the morphology of Langmuir monolayers at the
      air/water interface. The use of the BAM for attaining structural insights in the
      molecular arrangement of the Langmuir monolayers is widespread. In this review,
      we examine the reflection of a Langmuir monolayer under a rather different
      perspective than classical: the influence of the polar headgroup of the
      amphiphiles in the BAM images is taken into account. The relevance of the polar
      headgroup as the main cause of the BAM features has been the focus of a reduced
      number of BAM studies. An emerging experimental and theoretical framework from
      recent bibliography is discussed. Different theoretical scenarios are considered,
      concerning the size and absorption of radiation of the polar headgroup. Two
      qualitative examples showing physical phenomena regarding the reflectivity
      changes in a BAM experiments are discussed. The anisotropy in the BAM images as
      inner textures is of special interest. Quantitative structural information of the
      molecular arrangement of the monolayer is obtained by simulating the textures of
      the domains observed. The quantitative assessment of the detailed molecular
      arrangement of the polar headgroup by BAM is highly valuable, as this information
      can hardly be obtained from other experimental techniques. The procedure for
      extracting quantitative structural data from the experimental BAM pictures is
      revised in detail from the recent bibliography for further application of this
      model to different Langmuir monolayers.

PMID- 22397864
TI  - [Laboratory diagnosis of fungal infection diseases].
AB  - A number of newer diagnostic procedures have been developed over the last few
      years as alternatives to conventional microbiological methods to detect invasive
      fungal diseases (IFD). This text reviews the performance of alternative methods
      in clinical settings, and their accuracy compared with that of microscopical
      examination and microbiological cultures. Some newer techniques considered as
      complementary and experimental procedures are also reviewed. The text is divided
      into three sections, including Candida infections, aspergillosis and infections
      due to rare and emerging fungal species.

PMID- 22397865
TI  - [Sternal tumour in a 46-year-old woman].

PMID- 22397866
TI  - Role of serotonergic system in the pathogenesis of fibrosis in canine idiopathic
      inflammatory myopathies.
AB  - Idiopathic inflammatory myopathies are muscle diseases characterized by
      inflammation, necrosis, and fibrosis. The neurotransmitter serotonin (5-HT) has
      been shown to promote fibrosis in many tissues and organs by activating TGFbeta-1
      signaling. In this study, we evaluated the potential role of 5-HT in the
      pathogenesis of fibrosis in canine idiopathic inflammatory myopathies. Muscle
      biopsies from dogs affected by masticatory muscle myositis or polymyositis and
      from healthy dogs were processed for immunohistochemistry and Western blotting.
      The immunohistochemical analysis showed a strong expression of 5-HT in muscle
      tissues of affected dogs, whereas the amine was absent in the muscles of healthy
      dogs. Biochemical analysis showed increased expression levels of the selective 5
      HT2A receptor in the muscle specimens of the most severely affected dogs versus
      controls. Further, increased phosphorylation levels of the TGFbeta-1 signaling
      mediators SMAD2/3 and ERK1/2 were detected in tissue samples from affected dogs
      as compared to tissues from healthy dogs. Although further studies are needed,
      our findings highlight for the first time a potential role of 5-HT in the
      development of fibrosis in canine idiopathic inflammatory myopathies, thus
      supporting other evidence that 5-HT pro-fibrotic activity occurs via activation
      of TGFbeta-1 signaling pathway.

PMID- 22397867
TI  - Cavitatory lung disease in thoracic transplant recipients receiving sirolimus.
AB  - Sirolimus is a potent immunosuppressant agent that has utility in solid-organ
      transplantation (SOT), particularly for its renal-sparing effects. However, lung
      toxicity can be a significant issue and a variety of different lung injury
      patterns have been described. We report an unrecognized association of sirolimus
      with lung cavitation in patients who have undergone cardiothoracic
      transplantation. Between 1996 and 2010, lung and heart transplant patients
      received sirolimus-based immunosuppression as a second-line agent after initial
      therapy with calcineurin inhibitors. All cases of sirolimus-induced lung cavities
      were recorded and a retrospective review of the case notes of these patients was
      undertaken. A total of 9 patients were identified. Clinical symptoms, time to
      first cavity and mean levels were variable. Some patients showed complete
      resolution, whereas others had persistent cavitatory lung lesions. Patients who
      developed persistent lung cavities had a worse outcome than those who did not
      have cavitation.

PMID- 22397868
TI  - Listeria monocytogenes and diet during pregnancy; balancing nutrient intake
      adequacy v. adverse pregnancy outcomes.
AB  - OBJECTIVE: To evaluate the impact of adherence to public health recommendations
      on Listeria monocytogenes food safety to limit exposure to potential food sources
      on micronutrient intakes of pregnant women and whether more frequent consumption
      of 'high-risk' foods increases risk for adverse pregnancy outcomes. DESIGN: A
      cohort study in women assessing Listeria exposure from an FFQ based on
      consumption of potential Listeria-containing food sources, the Listeria Food
      Exposure Score (LFES). Pregnancy status was defined as pregnant, trying to
      conceive, had a baby within the previous 12 months, or other. Nutrient intakes
      were compared with Nutrient Reference Values and self-reported pregnancy outcome
      history three years later. SETTING: Australia. SUBJECTS: Women aged 25-30 years
      (n 7486) participating in the Australian Longitudinal Study on Women's Health.
      RESULTS: There were weak positive correlations (r = 0.13-0.37, P < 0.001) between
      LFES and all nutrients, with fibre, folate, Fe and vitamin E intakes consistently
      below the Nutrient Reference Values in every quintile of LFES. Women in the
      highest quintile of LFES reported 19 % more miscarriages (rate ratio = 1.19; 95 %
      CI 1.02, 1.38) than those in the lowest quintile, after adjusting for important
      confounding factors. CONCLUSIONS: More frequent consumption of foods potentially
      containing L. monocytogenes is associated with higher nutrient intakes, but an
      increased risk of miscarriage. L. monocytogenes pregnancy recommendations require
      review and should include the list of 'risky' food items in addition to low-risk
      alternatives that would adequately replace nutrient intakes which may be reduced
      through avoidance strategies.

PMID- 22397869
TI  - Is tissue inhibitor of metalloproteinase-1 a new prognosticator for breast
      cancer? An analysis of 266 cases.
AB  - Overexpression of tissue inhibitor of metalloproteinase-1 at either the messenger
      RNA or protein level has been related to a poorer prognosis in breast cancer. We
      investigated the role of tissue inhibitor of metalloproteinase-1 tissue
      expression, which was evaluated by immunohistochemistry staining of paraffin
      embedded samples, as a possible prognostic indicator in breast cancer. The study
      included 266 patients treated by primary surgery. Tumors were scored tissue
      inhibitor of metalloproteinase-1 positive when at least 10% of the cells showed
      moderate or strong staining. Staining was observed in 76 (28.6%) patients; by
      multivariate analysis, factors independently associated with tissue inhibitor of
      metalloproteinase-1 positivity included more than 9 metastatic axillary nodes,
      high Mib-1 expression, and positivity for plasminogen activator inhibitor and
      CD44. With a median follow-up of 125 months, tissue inhibitor of
      metalloproteinase-1 expression showed a significant prognostic role in disease
      free and overall survival by univariate analysis. Multivariate analysis confirmed
      an independent negative prognostic impact of tissue inhibitor of
      metalloproteinase-1 on overall but not disease-free together with high values of
      Mib-1. The number of involved axillary nodes, and triple negativity were
      independent predictors of either poorer disease-free or overall survival. In our
      study, tissue inhibitor of metalloproteinase-1 expression was significantly
      related to markers of tumor aggressiveness and was a powerful indicator of poorer
      prognosis, with a difference in 10-year disease-free and overall survival of 14%
      and 28%, respectively, between tissue inhibitor of metalloproteinase-1-negative
      and tissue inhibitor of metalloproteinase-1-positive cases. Expression of tissue
      inhibitor of metalloproteinase-1 also was an independent prognostic factor in
      node-positive cases, indicating a possible role of tissue inhibitor of
      metalloproteinase-1 as a marker of reduced chemosensitivity. Thus, tissue
      inhibitor of metalloproteinase-1 may have a role in clinical practice as a
      prognostic and predictive factor and a possible target for future therapies.

PMID- 22397870
TI  - Urethral caruncle: clinicopathologic features of 41 cases.
AB  - Urethral caruncle is a benign polypoid mass of the urethral meatus in primarily
      postmenopausal women. Although a conclusive association with malignancy, urologic
      disorder, or systemic disease has not been established, often the lesion carries
      a challenging clinical differential diagnosis that includes malignancy.
      Conversely, unexpected malignancy is identified in some cases resembling caruncle
      clinically. We examined clinical and histopathologic characteristics in 41
      patients. Medical records were assessed for presentation, clinical diagnosis,
      associated urothelial carcinoma, radiation treatment, tobacco use,
      immunologic/urologic disorder, and treatment strategy/outcome. Average patient
      age was 68 years (range, 28-87 years). Presenting symptoms were pain (37%),
      hematuria (27%), and dysuria (20%), in contrast to asymptomatic (32%). Clinical
      diagnosis favored malignancy in 10% of cases. Concurrent or subsequent urothelial
      carcinoma was present for 5 patients (12%), although none developed urethral
      carcinoma. Histologic features included mixed hyperplastic urothelial and
      squamous lining, overlying a variably fibrotic, edematous, inflamed, and vascular
      stroma. Invaginations of urothelium extending into the stroma were common (68%),
      showing rounded nests with cystic or glandular luminal spaces, similar to
      urethritis cystica/glandularis, without intestinal metaplasia. Two lesions
      included an organizing thrombus, 1 with intravascular papillary endothelial
      hyperplasia. Twenty patients were treated with topical medications without
      resolution. Three lesions recurred (7%) after excision. A subset of patients had
      history of smoking or previous pelvic irradiation. Urethral caruncle is an
      uncommon lesion that may clinically mimic benign and malignant conditions.
      Awareness of the spectrum of clinical and histologic differential diagnoses is
      important in dealing with this unusual disease.

PMID- 22397871
TI  - Reversion-inducing cysteine-rich protein with Kazal motif (RECK) expression: an
      independent prognostic marker of survival in colorectal cancer.
AB  - Patient prognosis in colorectal cancer is determined as in most solid cancers by
      the extent of local invasion and the presence of lymph node and distant
      metastases. The invasive potential of a tumor depends on the ability to degrade
      extracellular matrix proteins, for example, by matrix metalloproteinases. An
      important inhibitor of matrix metalloproteinases is reversion-inducing cysteine
      rich protein with Kazal motifs (RECK), a membrane-anchored glycoprotein. This
      study investigated the prognostic relevance of RECK expression in colorectal
      cancer in a cohort of 283 patients. Analysis of immunohistochemical tissue
      microarray data showed that RECK protein levels did not seem to correlate with
      clinicopathologic parameters (Spearman rank correlation coefficients between 
      0.14 and -0.18) and that decreased RECK expression was an independent prognostic
      factor of poor survival, with a mean survival of 70 months in RECK-negative (146
      cases) versus 97 months in RECK-positive patients (137 cases) (log-rank test, P =
      .002).

PMID- 22397872
TI  - Histopathological characterization of cholecystectomy specimens in patients with
      inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: Inflammatory bowel disease is associated with increased risk
      of cholelithiasis. However, the histologic patterns in gallbladders have not been
      extensively studied. This study is designed to characterize the histopathologic
      features of cholecystectomy specimens in inflammatory bowel disease patients,
      compared to a control group. METHODS: Cholecystectomy specimens in 78 Crohn's
      disease patients and 50 ulcerative colitis patients were reviewed. These were
      compared with 93 cholecystomies from noninflammatory bowel disease patients of
      approximate age and sex. The pattern and extent of inflammation was noted.
      RESULTS: Marked chronic cholecystitis was present in 12% of ulcerative colitis
      patients (P<0.05) and 10.3% of Crohn's disease patients (P>0.05), compared to
      4.3% of the noninflammatory bowel disease control group. Eight percent of
      ulcerative colitis patients (P<0.05) and 2.6% of Crohn's disease patients
      (P>0.05) had acute serositis, compared to 0% of the noninflammatory bowel disease
      control. The third inflammatory pattern, nodular lymphoid aggregates, was
      significantly increased in Crohn's disease patients after adjusting for the
      effect of cholelithiasis. Nodular lymphoid aggregates were found in 21.2% of
      Crohn's disease patients and 9.7% of ulcerative colitis patients without
      cholelithiasis, compared to 5% of noninflammatory bowel disease controls without
      cholelithiasis, a statistically significant difference between the Crohn's
      disease and control groups (P<0.05). CONCLUSIONS: Inflammatory bowel disease
      patients show similar inflammatory patterns in cholecystectomy specimens compared
      to the general population. However, two inflammatory patterns that occur more
      often in ulcerative colitis patients are marked chronic cholecystitis and acute
      serositis, while nodular lymphoid aggregates are more common in Crohn's disease
      patients.

PMID- 22397873
TI  - Women show worse control of type 2 diabetes and cardiovascular disease risk
      factors than men: results from the MIND.IT Study Group of the Italian Society of
      Diabetology.
AB  - BACKGROUND AND AIMS: The study explores the degree of control of hyperglycaemia
      and cardiovascular (CV) disease risk factors in men and women with type 2
      diabetes and the impact thereon of obesity, central adiposity, age and use of
      medications. METHODS AND RESULTS: A cross-sectional survey was conducted at 10
      hospital-based outpatients diabetes clinics. 1297 men and 1168 women with no
      previous CV events were studied. Women were slightly (only one year) older and
      more obese than men: average BMI was respectively 30.7 +/- 5.7 vs 28.6 +/- 4.1
      kg/m(2) (p < 0.001), and prevalence of abdominal obesity was 86% vs 44% (p <
      0.001). Women smoked less, but had higher HbA1c, LDL cholesterol, non-HDL
      cholesterol, systolic blood pressure and serum fibrinogen than men. Accordingly
      optimal targets for HbA1c (<7%), LDL cholesterol (<100 mg/dL), HDL cholesterol
      (>40 for men, >50 for women, mg/dL), and systolic blood pressure (<130 mmHg) were
      less frequently achieved by women than men (respectively 33.8% vs 40.2%; 14.6% vs
      19.2%; 34.1% vs 44.5%; 68.8% vs 72%; p < 0.05 for all). Findings were confirmed
      after stratification for waist circumference (< or >= 88 cm for women; < or >=
      102 cm for men), BMI (< or >= 25 kg/m(2)) or age (< or >= 65 years). As for
      treatment, women were more likely than men to take insulin, alone or in
      combination with oral hypoglycaemic drugs, to be under anti-hypertensive
      treatment, whereas the use of lipid lowering drugs was similar in men and women.
      CONCLUSIONS: Control of hyperglycaemia and major CVD risk factors is less
      satisfactory in women than men. The gender disparities are not fully explained by
      the higher prevalence of total and central obesity in women; or by a less
      intensive medical management in women.

PMID- 22397874
TI  - Macrophage polarization: the answer to the diet/inflammation conundrum?
AB  - Macrophages, a heterogeneous and ubiquitous cell population representing up to
      15% of the cellular content of different types of tissue, are the principal cell
      mediators in response to pathogens, inflammation process, tissue homeostasis and
      repair and play a pivotal role in atherosclerosis and insulin resistance because
      of their capacity to be the major source of inflammatory cytokines, which can
      function through paracrine and endocrine mechanisms. Recently, differently
      activated macrophage populations have been described, depending on a large
      variety of microenvironmental signals, and it is now recognized that their
      activation plays a crucial role in the development and progression of
      atherosclerosis. There is good evidence of the ability of conjugated linoleic
      acids and polyphenolic compounds to modulate inflammation in experimental models
      involving macrophages. This observation leaves room to the intriguing hypothesis
      that macrophage polarization could represent one of the unifying mechanisms
      through which specific food components can exert anti-inflammatory effects in
      humans, contributing to the prevention of chronic diseases strongly linked to
      inflammation, such as atherosclerosis. Future studies should be addressed to
      substantiate this hypothesis, investigating whether or not physiological
      concentrations of food-derived metabolites can perturb macrophage activation in
      vitro. On the in vivo side, the evaluation of macrophage populations in tissues,
      however complex, should be included among the analyses performed in observational
      and intervention studies, in order to understand if macrophage activation is
      involved in the anti-inflammatory activity of a specific dietary regimen.

PMID- 22397875
TI  - Effects of a nutraceutical combination on left ventricular remodeling and
      vasoreactivity in subjects with the metabolic syndrome.

PMID- 22397876
TI  - No association between the degree of liver steatosis and early signs of
      vasculopathy in T2DM.

PMID- 22397878
TI  - Altering source or amount of dietary carbohydrate has acute and chronic effects
      on postprandial glucose and triglycerides in type 2 diabetes: Canadian trial of
      Carbohydrates in Diabetes (CCD).
AB  - BACKGROUND AND AIMS: Nutrition recommendations for type 2 diabetes (T2DM) are
      partly guided by the postprandial responses elicited by diets varying in
      carbohydrate (CHO). We aimed to explore whether long-term changes in postprandial
      responses on low-glycemic-index (GI) or low-CHO diets were due to acute or
      chronic effects in T2DM. METHODS AND RESULTS: Subjects with diet-alone-treated
      T2DM were randomly assigned to high-CHO/high-GI (H), high-CHO/low-GI (L), or low
      CHO/high-monounsaturated-fat (M) diets for 12-months. At week-0 (Baseline)
      postprandial responses after H-meals (55% CHO, GI = 61) were measured from 0800 h
      to 1600 h. After 12 mo subjects were randomly assigned to H-meals or study diet
      meals (L, 57% CHO, GI = 50; M, 44% CHO, GI = 61). This yielded 5 groups: H diet
      with H-meals (HH, n = 34); L diet with H- (LH, n = 17) or L-meals (LL, n = 16);
      and M diet with H- (MH, n = 18) or M meals (MM, n = 19). Postprandial glucose
      fluctuations were lower in LL than all other groups (p < 0.001). Changes in
      postprandial-triglycerides differed among groups (p < 0.001). After 12 mo in HH
      and MM both fasting- and postprandial-triglycerides were similar to Baseline
      while in MH postprandial-triglycerides were significantly higher than at Baseline
      (p = 0.028). In LH, triglycerides were consistently (0.18-0.34 mmol/L) higher
      than Baseline throughout the day, while in LL the difference from Baseline varied
      across the day from 0.04 to 0.36 mmol/L (p < 0.001). CONCLUSION: Low-GI and low
      CHO diets have both acute and chronic effects on postprandial glucose and
      triglycerides in T2DM subjects. Thus, the composition of the acute test-meal and
      the habitual diet should be considered when interpreting the nutritional
      implications of different postprandial responses.

PMID- 22397879
TI  - Sarcopenic obesity is associated with adverse clinical outcome after cardiac
      surgery.
AB  - BACKGROUND & AIMS: Both undernutrition - low fat free mass (FFM) - and obesity -
      high fat mass (FM) - have been associated with adverse outcome in cardiac
      surgical patients. However, whether there is an additional effect on outcome of
      these risk factors present at the same time, that is sarcopenic obesity (SO), is
      unknown. Furthermore, the association between SO and muscle function is
      unidentified. METHODS AND RESULTS: In 325 cardiac surgical patients, we
      prospectively analysed the association between preoperative FFM and FM, measured
      by bioelectrical impedance spectroscopy, and postoperative adverse outcomes, and
      their correlation with muscle function - handgrip strength (HGS). SO was
      associated with postoperative infections (28.2% vs. 5.3%, adj. odds ratio (OR):
      7.9; 95% confidence interval (CI): 1.2-54.1; p=0.04). Further, a low FFM index
      (FFMI; kgm(-2)) was associated with postoperative infections (18.5% vs. 4.7%,
      adj. OR: 6.6; 95% CI: 1.7-25.2; p=0.01) while a high FM index (FMI; kgm(-2)) was
      not. Both components of SO, FFMI and FMI, correlated with HGS (FFMI: r=0.570;
      p<0.001, FMI: r=-0.263; p<0.001). CONCLUSION: SO is associated with an increased
      occurrence of adverse outcome after cardiac surgery. Our results suggest an
      additional risk of a low FFMI and high FMI present at the same time. Furthermore,
      SO is characterised by less muscle function. We advocate determining body
      composition in cardiac surgical patients to classify and treat undernourished
      patients, in particular those who are also obese.

PMID- 22397880
TI  - Common variants in SOCS7 gene predict obesity, disturbances in lipid metabolism
      and insulin resistance.
AB  - BACKGROUND AND AIMS: Specific Suppressor of Cytokine Signaling (SOCS) members,
      such as SOCS7, may play a role in the development of insulin resistance (IR)
      owing to their ability to inhibit insulin signaling pathways. The objective was
      to explore the association between common variants and related haplotypes in
      SOCS7 gene and metabolic traits related to obesity, lipid metabolism and IR.
      METHODS AND RESULTS: 780 unrelated men were included in a cross-sectional study.
      We selected three tagged SNPs that capture 100% of SNPs with minor allele
      frequency >= 0.10. Analyses were done separately for each SNP and followed up by
      haplotype analysis. rs8074124C was associated with both obesity (p = 0.005) and
      abdominal obesity (p = 0.002) and allele C carriers showed, in comparison with TT
      carriers, lower BMI (p = 0.001) and waist circumference (p = 0.001). rs8074124CC-
      carriers showed lower fasting insulin (p = 0.017) and HOMA-IR (p = 0.018) than
      allele T carriers. rs12051836C was associated with hypertriglyceridemia (p =
      0.009) and hypertriglyceridemic waist (p = 0.006). rs12051836CC- carriers showed
      lower fasting insulin (p = 0.043) and HOMA-IR (p = 0.042). Haplotype-based
      association analysis (rs8074124 and rs12051836 in that order) showed associations
      with lipid and obesity -related phenotypes, consistent with single locus
      analysis. Haplotype analysis also revealed association between haplotype CT and
      both decreased HDL-C (p = 0.026) and HDL-C (p = 0.014) as a continuous variable.
      CONCLUSIONS: We found, for the first time, significant associations between SOCS7
      common variants and related haplotypes and obesity, IR and lipid metabolism
      disorders.

PMID- 22397881
TI  - Fat distribution, physical activity and cardiovascular risk among adolescent
      girls.
AB  - BACKGROUND AND AIMS: It is not clear whether changes in waist circumference (WC),
      sums of skinfold thickness (SSF), or levels of physical activity (PA) during
      adolescence are associated with cardiovascular risk factors, or if associations
      are independent or interactive. METHODS AND RESULTS: In a US cohort of adolescent
      girls (n = 617-904) girls, examined at ages 12 and 14, WC, SSF, PA, systolic and
      diastolic blood pressure (SBP & DBP) were assessed. Fasting blood samples were
      used to determine concentrations of triglycerides (TG), cholesterol (TC), high
      and low density lipoproteins (HDL-C and LDL-C), and apolipoprotein A1 and B (Apo
      A1 and Apo-B). After adjustment for change in SSF and PA, increases in WC were
      associated with change in TG (z = 1.73, 95% CI = 0.77, 2.69), TC (z = 0.45, 95%
      CI = 0.01, 0.90), HDL-C (z = -0.18, 95% CI = -0.37, -0.01), LDL-C (z = 0.41, 95%
      CI = 0.03, 0.80), Apo-A1 (z = -0.52, 95% CI = -1.02, -0.02), Apo-B (z = 0.60, 95%
      CI = 0.24, 0.97) and SBP levels (z = 0.31, 95% CI = 0.15, 0.47). Associations
      between changes in SSF and PA with cardiovascular risk were eliminated after
      adjustment for WC, and all interactions between WC, SSF and PA were non
      significant at conventional levels. CONCLUSIONS: Changes in WC were independently
      associated with the development of cardiovascular risk factors, whereas changes
      in SSF and PA were not. Clinicians should consider the routine screening of WC to
      monitor cardiovascular health in adolescent girls.

PMID- 22397882
TI  - Salt intake during pregnancy alters offspring's myocardial structure.
AB  - BACKGROUND AND AIM: To evaluate the effects of low or high salt intake during
      pregnancy on left ventricle of adult male offspring. METHODS AND RESULTS: Low-
      (LS, 0.15%), normal- (NS, 1.3%) or high-salt (HS, 8% NaCl) diet was given to
      Wistar rats during pregnancy. During lactation all dams received NS as well as
      the offspring after weaning. To evaluate cardiac response to salt overload, 50%
      of each offspring group was fed a high-salt (hs, 4% NaCl) diet from the 21st to
      the 36th week of age (LShs, NShs, HShs). The remaining 50% was maintained on NS
      (LSns, NSns and HSns). Echocardiography was done at 20 and 30 weeks of age. Mean
      blood pressure (MBP), histology and left ventricular angiotensin II content (AII)
      were analyzed at 36 weeks of age. Interventricular septum, left ventricular
      posterior wall and relative wall thickness increased from the 20th to the 30th
      week of age only in HShs, cardiomyocyte mean volume was higher in HShs compared
      to NShs, LShs and HSns. AII and left ventricular fibrosis were not different
      among groups. CONCLUSIONS: HS during pregnancy programs adult male offspring to a
      blood pressure and angiotensin II independent concentric left ventricular
      hypertrophy, with no fibrosis, in response to a chronic high-salt intake.

PMID- 22397877
TI  - Physical activity attenuates the negative effect of low birth weight on leptin
      levels in European adolescents; the HELENA study.
AB  - We examined whether physical activity (PA) influences the association between
      birth weight and serum leptin in adolescents. The study comprised a total of 538
      adolescents (315 girls), aged 12.5-17.49 years, born at term (>= 37 weeks of
      gestation). We measured serum leptin levels and time engaged in moderate-vigorous
      PA (MVPA) by accelerometry. There was an interaction effect between birth weight
      and meeting the PA recommendations (60 min/day MVPA) on leptin levels in girls (P
      = 0.023) but not in boys (P = 0.809). Birth weight was negatively associated with
      leptin levels in girls not meeting the PA recommendations (i.e. more than 60
      min/day of MVPA) (beta = -0.096, P = 0.009), whereas no significant association
      was observed in those meeting the PA recommendations (beta = -0.061, P = 0.433).
      In conclusion, meeting the PA recommendations may attenuate the negative effect
      of low birth weight on serum leptin levels in European female adolescents.

PMID- 22397883
TI  - Safety and efficacy of high-protein diets for weight loss.
AB  - Dietary strategies that can help reduce hunger and promote fullness are
      beneficial for weight control, since these are major limiting factors for
      success. High-protein (HP) diets, specifically those that maintain the absolute
      number of grams ingested, while reducing energy, are a popular strategy for
      weight loss (WL) due to the effects of protein-induced satiety to control hunger.
      Nonetheless, both the safety and efficacy of HP WL diets have been questioned,
      particularly in combination with low-carbohydrate advice. Nonetheless, for short
      to-medium-term intervention studies (over several months), increasing the
      energetic contribution of protein does appear effective. The effects of HP diets
      on appetite, bone health, renal function, blood pressure, cardiovascular bio
      markers, antioxidant status, gut health and psychological function are discussed.
      Further research is warranted to validate the physiological effects of HP diets
      over longer periods of time, including studies that modify the quality of
      macronutrients (i.e. the type of carbohydrate, fat and protein) and the
      interaction with other interventions (e.g. exercise and dietary supplements).

PMID- 22397884
TI  - Expanding nature's small molecule diversity via in vitro biosynthetic pathway
      engineering.
AB  - The enormous pool of chemical diversity found in nature serves as an excellent
      inventory for accessing biologically active compounds. This chemical inventory,
      primarily found in microorganisms and plants, is generated by a broad range of
      enzymatic pathways under precise genetic and protein-level control. In vitro
      pathway reconstruction can be used to characterize individual pathway enzymes,
      identify pathway intermediates, and gain an increased understanding of how
      pathways can be manipulated to generate natural product analogs. Moreover,
      through in vitro approaches, it is possible to achieve a diversification that is
      not restricted by toxicity, limited availability of intracellular precursors, or
      preconceived (by nature) regulatory controls. Additionally, combinatorial
      biosynthesis and high-throughput techniques can be used to generate both known
      natural products and analogs that would not likely be generated naturally. This
      current opinion review will focus on recent advances made in performing in vitro
      pathway-driven natural product diversification and opportunities for exploiting
      this approach for elucidating and entering this new chemical biology space.

PMID- 22397885
TI  - Electron transfer in nitrogenase catalysis.
AB  - Nitrogenase is a two-component enzyme that catalyzes the nucleotide-dependent
      reduction of N2 to 2NH3. This process involves three redox-active metal
      containing cofactors including a [4Fe-4S] cluster, an eight-iron P cluster and a
      seven-iron plus molybdenum FeMo-cofactor, the site of substrate reduction. A
      deficit-spending model for electron transfer has recently been proposed that
      incorporates protein conformational gating that favors uni-directional electron
      transfer among the metalloclusters for the activation of the substrate-binding
      site. Also reviewed is a proposal that each of the metal clusters cycles through
      only two redox states of the metal-sulfur core as the system accumulates the
      multiple electrons required for substrate binding and reduction. In particular,
      it was suggested that as FeMo-cofactor acquires the four electrons necessary for
      optimal binding of N2, each successive pair of electrons is stored as an Fe-H--Fe
      bridging hydride, with the FeMo-cofactor metal-ion core retaining its resting
      redox state. We here broaden the discussion of stable intermediates that might
      form when FeMo-cofactor receives an odd number of electrons.

PMID- 22397886
TI  - [Cutaneous tuberculosis in an area of Mallorca (2003-2011)].
AB  - BACKGROUND AND OBJECTIVE: Tuberculosis is an important health care problem, even
      in our setting. The objective of this study is to describe clinic and
      epidemiological features of cutaneous tuberculosis in our area. PATIENTS AND
      METHODS: A retrospective study was performed of all patients diagnosed of
      cutaneous tuberculosis in a hospital in Mallorca (Spain) from January 2003 to
      July 2011. The clinical forms, diagnostic methods used, treatment used and
      clinical course were recorded. RESULTS: Twenty-eight cases of cutaneous
      tuberculosis were diagnosed (5.9% of the tuberculosis cases diagnosed in this
      period), 15 with classic cutaneous tuberculosis (14 scrofuloderma, 1 empyema
      necessitatis) and 13 patients with tuberculids (8 erythema induratum of Bazin
      disease and 5 erythema nodosum). Scrofulodermas came from lymph nodes in 10 of
      the patients, infected bone in 4 and pleural in one case; 13/28 patients came
      from other continents. Most of the patients were treatment with 3-4
      tuberculostatic drugs, with favorable course. CONCLUSIONS: Cutaneous tuberculosis
      is not uncommon in our setting. In classic cutaneous tuberculosis culture is the
      gold standard diagnostic method while tuberculids are most commonly diagnosed by
      histology.

PMID- 22397887
TI  - [Guideline to prevent claims due to medical malpractice, on how to act when they
      do occur and how to defend oneself through the courts].
AB  - Claims due to presumed medical malpractice are increasing in all developed
      countries and many of them have no basis. To prevent legal complaints, the
      physicians should know the reasons why complaints are made by their patients and
      adopt the adequate preventive measures. In the case of a complaint, it is
      essential to follow the guidelines that allow for adequate legal defense and the
      action of the physician before the judge that inspires confidence and
      credibility. The risk of the claims can be reduced with adequate information to
      the patient, the following of the clinical guidelines, control of the risk
      factors and adoption of verification lists in each invasive procedure. In case of
      complication or serious adverse effect, explanations should be given to the
      patient and family and it should be reported to the facility where one works and
      to the insurance company. If the physician received a claim, he/she should report
      it to the insurance compare so that it can name a lawyer responsible for the
      legal defense who will advise the physician regarding the appearance in court
      before the judge.

PMID- 22397888
TI  - Undiagnosed bipolar disorder in patients treated for major depression in China.
AB  - BACKGROUND: Bipolar disorder (BD) is a recurrent, complex illness and often
      misdiagnosed and treated as a major depressive disorder (MDD). This study set out
      (1) to investigate the proportion of BD in patients treated for MDD using DSM-IV
      diagnostic criteria; (2) to test the usefulness of the screening tool - the 32
      item Hypomania Checklist (HCL-32) in Chinese patients; and (3) to assess whether
      MDD patients with subthreshold manic features (patients who screened positive for
      BD on the HCL-32, but did not meet the diagnostic criteria for DSM-IV BD as
      measured by Mini International Neuropsychiatric Interview (MINI)) differ from
      those with BD, and from those suffering from MDD without manic features in terms
      of basic demographic and clinical variables. METHODS: A total of 1487 patients
      treated for MDD were consecutively examined in 13 mental health centers in China.
      The patients' socio-demographic and clinical characteristics were recorded using
      a standardized protocol and data collection procedure. The HCL-32 was self
      completed by patients to identify hypomanic symptoms, and the MINI was used by
      clinicians to establish DSM-IV diagnoses. RESULTS: The proportions of undiagnosed
      BD (all types), BD-I and BD-II were 20.8%, 7.9% and 12.8%, respectively. The HCL
      32 had low positive predictive value (0.43). Compared to MDD patients without
      subthreshold manic features, MDD patients with subthreshold manic features were
      younger at onset, less likely to be married and had more depressive episodes on a
      seasonal basis, and more frequent depressive episodes overall. Compared to BD
      patients, MDD patients with subthreshold manic features had an older age at onset
      and less frequent depressive episodes and less family history of psychiatric
      disorders, appetite, weight gain and time spent sleeping, suicide ideation and
      attempts and psychotic symptoms. CONCLUSIONS: At least one fifth of Chinese
      patients treated for MDD may have an undiagnosed BD. The HCL-32 is useful to
      identify broader subthreshold bipolar features. The findings need to be confirmed
      by longitudinal studies using more comprehensive, standardized instruments.

PMID- 22397890
TI  - A double blind randomized trial of unilateral left and bilateral prefrontal
      cortex transcranial magnetic stimulation in treatment resistant major depression.
AB  - OBJECTIVE: A substantive body of research has demonstrated the efficacy of
      repetitive transcranial magnetic stimulation treatment (rTMS) in patients with
      depression. However, the parameters needed to optimize therapeutic efficacy
      remain unclear. The aim of this study was to investigate whether there is an
      advantage in efficacy of sequential bilateral rTMS compared to standard high
      frequency left sided rTMS. METHOD: Sixty seven patients with treatment resistant
      depression were included in a randomised double-blind sham controlled trial of
      sequential bilateral rTMS compared to standard high-frequency left sided rTMS and
      sham rTMS over a three-week period. The study also included a further three week
      comparison of the two active treatment conditions. The primary outcome variable
      was scores on the 17-item Hamilton Depression Rating Scale (HAMD). RESULTS: In
      the three-week double-blind phase of the trial there was a greater antidepressant
      response to unilateral left sided rTMS compared with sham or bilateral rTMS.
      Across the full six weeks of active rTMS, there was also a consistent pattern of
      improved response in unilateral left compared to bilateral treatment. Response
      rates were low in both active groups. CONCLUSIONS: This study does not support
      the hypothesis that sequential bilateral rTMS is more effective than unilateral
      high-frequency left-sided rTMS.

PMID- 22397889
TI  - Pretreatment cerebral metabolic activity correlates with antidepressant efficacy
      of vagus nerve stimulation in treatment-resistant major depression: a potential
      marker for response?
AB  - BACKGROUND: Pretreatment brain activity in major depressive disorder correlates
      with response to antidepressant therapies, including pharmacotherapies and
      transcranial magnetic stimulation. The purpose of this trial was to examine
      whether pretreatment regional metabolic activity in selected regions of interest
      (ROIs) predicts antidepressant response following 12 months of vagus nerve
      stimulation (VNS) in 15 patients with treatment-resistant major depression
      (TRMD). METHODS: Fluorodeoxyglucose positron emission tomography (FDG PET) was
      used to assess regional mean relative cerebral metabolic rate for glucose
      (CMRGlu) in four ROIs (anterior insular, orbitofrontal, anterior cingulate, and
      dorsolateral prefrontal cortices) at baseline (prior to VNS activation).
      Depression severity was assessed at baseline and after 12 months of VNS using the
      Hamilton Depression Rating Scale (HDRS), with response defined as >= 50%
      reduction in HDRS from baseline. RESULTS: Baseline CMRGlu in the anterior insular
      cortex differentiated VNS responders (n=11) from nonresponders (n=4) and
      correlated with HDRS change (r=.64, p=.01). In a regression analysis, lower
      anterior insular cortex CMRGlu (p=.004) and higher orbitofrontal cortex CMRGlu
      (p=.047) together predicted HDRS change (R(2)=.58, p=.005). In a whole brain,
      voxel-wise analysis, baseline CMRGlu in the right anterior insular cortex
      correlated with HDRS change (r=.78, p=.001). LIMITATIONS: Sample size was small,
      limiting statistical power; patients remained on their psychiatric medications;
      study was open-label and uncontrolled. CONCLUSIONS: This preliminary study
      suggests that pretreatment regional CMRGlu may be useful in predicting response
      to VNS in TRMD patients.

PMID- 22397891
TI  - Nutrient intakes and the common mental disorders in women.
AB  - BACKGROUND: There is an increasing recognition of the role of nutrition in
      depression and anxiety. Magnesium, folate and zinc have all been implicated in
      depressive illness, however there are few data on these nutrients in anxiety
      disorders and the data from population-studies are limited. AIMS: In a large,
      randomly-selected, population-based sample of women, this study aimed to examine
      the relationship between the dietary intakes of these three micronutrients and
      clinically determined depressive and anxiety disorders and symptoms. METHODS:
      Nutrient intakes were determined using a validated food frequency questionnaire.
      The General Health Questionnaire-12 measured psychological symptoms, and a
      clinical interview (Structured Clinical Interview for DSM-IV-TR, non-patient
      edition) assessed current depressive and anxiety disorders. RESULTS: After
      adjustments for energy intake, each standard deviation increase in the intake of
      zinc, magnesium and folate was associated with reduced odds ratio (OR) for major
      depression/dysthymia (zinc: OR=0.52, 95% confidence interval (CI) 0.31 to 0.88;
      magnesium: OR=0.60, 95% CI 0.37 to 0.96; folate: OR=0.66, 95% CI 0.45 to 0.97).
      There was also an inverse association between the intake of magnesium and zinc
      and GHQ-12 scores (zinc: zbeta=-0.16, 95% CI -0.29 to -0.04; magnesium: -0.14,
      95% CI -0.26 to -0.03). These relationships were not confounded by age,
      socioeconomic status, education or other health behaviours. There was no
      relationship observed between any nutrient and anxiety disorders. CONCLUSION:
      These results demonstrate an association between the dietary intakes of
      magnesium, folate and zinc and depressive illnesses, although reverse causality
      and/or confounding cannot be ruled out as explanations.

PMID- 22397892
TI  - [Spanish normative studies in a young adult population (NEURONORMA young adults
      Project): methods and characteristics of the sample].
AB  - INTRODUCTION: In clinical neuropsychology, normative data are necessary to relate
      the performance of a subject to a reference group. These normative data should be
      collected from a pertinent population taking into account sociodemographic and
      cultural factors. OBJECTIVE: This paper describes the methods and sample
      characteristics of a series of Spanish normative studies on young adults
      (NEURONORMA young adults Project). The normative information was based on a
      series of selected, commonly used, neuropsychological tests covering attention,
      language, visual-perceptual abilities, constructional tasks, memory, and
      executive functions. MATERIAL AND METHODS: A sample of 179 cognitively normal
      subjects from 18 to 49 years was studied. Demographics, socio-cultural, and
      medical data were collected. The statistical procedure used in the normative
      studies is described. RESULTS: Sociodemographic, family background, health
      habits, medical history and use of drugs are presented. CONCLUSIONS: The use of
      these norms should improve neuropsychological diagnostic accuracy in young
      Spanish subjects. These data may also be of considerable use for comparisons with
      other normative studies.

PMID- 22397893
TI  - 'I deal with the small things': the doctor-patient relationship and professional
      identity in GPs' stories of cancer care.
AB  - An important part of GPs' work consists of attending to the everyday and
      existential conditions of human being. In these life world aspects, biomedicine
      is often not the relevant theory to guide the GP; nevertheless they are a part of
      GPs' professional domain. In cancer care, previous studies have shown that GPs
      with a biomedical perspective on medicine could feel subordinate to specialists,
      and that doctors with a curative focus could see disease progression as a
      personal failure. The aim of this study was to explore in depth the experiences
      of being a GP for people with advanced cancer. Fourteen Norwegian GPs were
      interviewed about accompanying patients through a cancer illness. Their stories
      were analysed using a narrative approach. The GPs expressed a strong commitment
      to these patients, a loyalty which in some cases could be weakened due to
      judgements of distant specialists. In view of the GPs' close knowledge of their
      patients' background and history this subordination was a paradox, mirroring a
      hierarchy of medical knowledge. The GPs had an ideal of honesty and openness
      about death, which they sometimes failed. To reach the ideal of honesty,
      clinicians would have to abandon the biomedical ideal of mastering human nature
      through interventions and acknowledge the fundamental uncertainty and finiteness
      of human life. GPs may learn from being with their patients that bodily and
      existential suffering are connected, and thus learn implicitly to overlook the
      body-mind dualism. This practical wisdom lacks a theoretical anchoring, which is
      a problem not only for general practice.

PMID- 22397894
TI  - On assisted living, are we hitting the mark or missing the boat?

PMID- 22397896
TI  - Role of core needle biopsy in the treatment of radial scar.
AB  - Invasive tumor or ductal carcinoma in situ occur in radial sclerosing lesions in
      one third of the cases therefore, surgical excision is mandatory. Forty-five
      patients with radial scar morphology were examined. Ultrasound guided fine-needle
      aspiration biopsy (FNAB) and core biopsy (CB) were performed in all cases. The
      postoperative pathological findings were compared to the results of preoperative
      biopsies. Sensitivity of preoperative percutaneous biopsies (FNAB and CB) was
      17.6% and 70.6%, false-negative rate was 82.4% with FNAB and 29.4% with CB. The
      negative predictive value was 48.1% and 84.8% respectively. Had we done
      preoperative cytology only, we would have had to perform a two-step procedure
      (sentinel lymph node biopsy) in 7 patients (15.6%), while with preoperative core
      biopsy it has decreased to 2 patients (4.4%). Preoperative CB in small radial
      stellate lesions is recommended to achieve accurate diagnosis in order to avoid a
      two-step surgical procedures.

PMID- 22397895
TI  - High prevalence of neuroendocrine carcinoma in breast lesions detected by the
      clinical symptom of bloody nipple discharge.
AB  - AIM: Bloody nipple discharge (BND) is an important clinical symptom in breast
      disorders, especially cancers. However, the association between this symptom and
      breast neuroendocrine carcinomas (NECs) has not been sufficiently investigated or
      well understood. METHODS: We clinicopathologically studied 89 cases using biopsy
      and/or resection in 144 patients who came to the hospital for a thorough
      examination of symptomatic BND. RESULTS: Of these 89 cases examined
      histologically, 24 (27%) were neuroendocrine carcinomas (NECs) in which >50% of
      cells immuno-expressed chromogranin A and/or synaptophysin. Moreover, NECs made
      up 44% (24/55) of the mammary cancers found because of the BND. The frequency of
      diagnosing malignancy preoperatively in 24 NECs was 4% by nipple discharge
      cytology, 40% by fine needle aspiration cytology, 62% by core needle biopsy and
      67% by mammotome biopsy. There were neither postoperative recurrences nor
      metastases in the NEC cases during a mean follow-up of 83.7 months. The 24 NECs
      were subclassified into neuroendocrine ductal carcinoma in situ (NE-DCIS) (9
      cases) and microinvasive (7 cases) and invasive (8 cases) NECs with extensive NE
      DCIS components. Most NECs had early-stage and low-grade pathological parameters:
      pTis or pT1 (96%), pN0 (96%), low nuclear grade (83%), absence of necrosis (88%),
      immuno-positivity of estrogen and progesterone receptors (100%) and absence of
      HER2 protein overexpression (100%). CONCLUSIONS: NECs predominantly with NE-DCIS
      lesions, often under-diagnosed preoperatively, accounted for an important share
      of breast conditions associated with BND. It is, therefore, worth keeping this
      type of breast cancer in mind when performing medical examinations on patients
      with BND.

PMID- 22397897
TI  - Prognosis of breast cancer in patients with peritoneal metastasis.

PMID- 22397898
TI  - Religious involvement and obsessive compulsive disorder among African Americans
      and Black Caribbeans.
AB  - Prior research is equivocal concerning the relationships between religious
      involvement and obsessive-compulsive disorder (OCD). The literature indicates
      limited evidence of denomination differences in prevalence of OCD whereas
      findings regarding OCD and degree of religiosity are equivocal. This study builds
      on prior research by examining OCD in relation to diverse measures of religious
      involvement within the National Survey of American Life, a nationally
      representative sample of African American and Black Caribbean adults. Bivariate
      and multivariate analyses (logistic regression) examine the relationship between
      lifetime prevalence of OCD and religious denomination, service attendance, non
      organizational religiosity (e.g., prayer, religious media) subjective
      religiosity, and religious coping. Frequent religious service attendance was
      negatively associated with OCD, whereas Catholic affiliation (as compared to
      Baptist) and religious coping (prayer when dealing with stressful situations)
      were both positively associated with OCD. With regard to demographic factors,
      persons of older age and higher education levels were significantly less likely
      to have OCD.

PMID- 22397899
TI  - Outcomes and predictors of failure of trocar-guided vaginal mesh surgery for
      pelvic organ prolapse.
AB  - OBJECTIVE: The objective of the study was to compare the 1 year conventional and
      composite outcomes of trocar-guided vaginal mesh surgery and the identification
      of the predictors of failure. STUDY DESIGN: This was a prospective observational
      cohort study. Failure outcome definitions were as follows: I, prolapse stage II
      or greater in mesh treated compartments; II, overall prolapse stage II or
      greater; III, composite outcome of overall prolapse greater than the hymen and
      the presence of bulge symptoms or repeat surgery. We used logistic regression to
      identify predictors of failure. RESULTS: The results of the study were 1 year
      follow-up of 433 patients. Treated compartment failure (I) was 15% (95%
      confidence interval [CI], 12-19). Overall prolapse failure (II) was 41% (95% CI,
      36-45). Composite failure (III) was 9% (95% CI, 7-13). Predictor of failure in
      all outcomes was the combined anterior/posterior mesh with the uterus in situ.
      CONCLUSION: Outcome of prolapse surgery depends on outcome definition. The mesh
      treated compartment failure outcome (I) and the composite failure outcome (III)
      appeared not to be statistically different. Consistent factor for failure in all
      outcomes was the combined anterior/posterior mesh insertion with the uterus in
      situ.

PMID- 22397900
TI  - Symptomatic and anatomic 1-year outcomes after robotic and abdominal
      sacrocolpopexy.
AB  - OBJECTIVE: The purpose of this study was to compare symptomatic and anatomic
      outcomes 1 year after robotic vs abdominal sacrocolpopexy. STUDY DESIGN: Our
      retrospective cohort study compared women who underwent robotic sacrocolpopexy
      (RSC) with 1 surgeon to those who underwent abdominal sacrocolpopexy (ASC) as
      part of the Colpopexy and Urinary Reduction Efforts trial. Our primary outcome
      was a composite measure of vaginal bulge symptoms or repeat surgery for prolapse.
      RESULTS: We studied 447 women (125 with RSC and 322 with ASC). Baseline
      characteristics were similar. There were no significant differences in surgical
      failures 1 year after surgery based on our primary composite outcome (7/86 [8%]
      vs 12/304 [4%]; P = .16). When we considered anatomic failure, there were also no
      significant differences between RSC and ASC (4/70 [6%] vs 16/289 [6%]; P = .57).
      CONCLUSION: One year after sacrocolpopexy, women who underwent RSC have similar
      symptomatic and anatomic success compared with those women who underwent ASC.

PMID- 22397901
TI  - Effect of surgical approach on physical activity and pain control after sacral
      colpopexy.
AB  - OBJECTIVE: We sought to compare recovery of activity and pain control after
      robotic (ROB) vs abdominal (ABD) sacral colpopexy. STUDY DESIGN: Women undergoing
      ROB and ABD sacral colpopexy wore accelerometers for 7 days preoperatively and
      the first 10 days postoperatively. They completed postoperative pain diaries and
      Short Form-36 questionnaires before and after surgery. RESULTS: At 5 days
      postoperatively, none of the 14 subjects in the ABD group and 4 of 28 (14.3%) in
      the ROB group achieved 50% total baseline activity counts (P = .283). At 10 days,
      5 of 14 (35.7%) in the ABD group and 8 of 26 (30.8%) in the ROB group (P = .972)
      achieved 50%. Postoperative pain was similar in both groups. Short Form-36
      vitality scores were lower (P = .017) after surgery in the ABD group, but not in
      the ROB group. CONCLUSION: Women undergoing ROB vs ABD sacral colpopexy do not
      recover physical activity faster, and pain control is not improved.

PMID- 22397902
TI  - Distribution of blood concentrations of persistent organic pollutants in a
      representative sample of the population of Barcelona in 2006, and comparison with
      levels in 2002.
AB  - INTRODUCTION: POP biomonitoring programs are useful for exposure assessment, to
      analyze patterns, and to evaluate policies. However, population-representative
      surveys are scarce and heterogeneous. Reports on time trends in representative
      samples using the same methods are rare. OBJECTIVES: To analyze the distribution
      of serum concentrations of 19 POPs in the general population of Barcelona city in
      2006, and to compare it with the distribution in 2002. METHODS: 231 participants
      in the Barcelona Health Survey were interviewed face-to-face, gave blood, and
      underwent a physical exam. Density plots ("POP Geoffrey Rose curves") were used
      to represent the full population distribution of each compound. RESULTS: Eight
      POPs were each detected in >80% of the study subjects: p,p'-DDT, p,p'-DDE, PCB
      congeners 118, 138, 153 and 180, HCB and beta-HCH. The minimum number of POPs
      detected in one person was 5, and 72% of the population accumulated >= 10
      compounds. p,p'-DDE and HCB showed the highest concentrations (median=219 and 109
      ng/g lipid, respectively). Concentrations decreased by 34-56% from 2002 to 2006.
      The decrease was similar in women and men, and in all age groups/birth cohorts.
      It was larger with increasing BMI; for p,p'-DDT, HCB and beta-HCH the decrease in
      obese individuals was 31-44 percentage points larger than in subjects with normal
      weight. The distribution of POP concentrations was always switched towards higher
      values in women than men. POP levels also differed significantly by age, body
      mass index, weight gain, birth place and social class, but not by parity and
      breastfeeding. The two younger cohorts had a higher DDT/DDE ratio than the oldest
      cohort. CONCLUSION: Although human POP contamination remains common in the city
      of Barcelona, concentrations decreased significantly in 4years. Our approach
      suggests innovative ways to conceive, analyze and present results for other
      monitoring programs.

PMID- 22397903
TI  - Food waste disposal units in UK households: the need for policy intervention.
AB  - The EU Landfill Directive requires Member States to reduce the amount of
      biodegradable waste disposed of to landfill. This has been a key driver for the
      establishment of new waste management options, particularly in the UK, which in
      the past relied heavily on landfill for the disposal of municipal solid waste
      (MSW). MSW in the UK is managed by Local Authorities, some of which in a less
      conventional way have been encouraging the installation and use of household food
      waste disposal units (FWDs) as an option to divert food waste from landfill. This
      study aimed to evaluate the additional burden to water industry operations in the
      UK associated with this option, compared with the benefits and related savings
      from the subsequent reductions in MSW collection and disposal. A simple economic
      analysis was undertaken for different FWD uptake scenarios, using the Anglian
      Region as a case study. Results demonstrated that the significant savings from
      waste collection arising from a large-scale uptake of FWDs would outweigh the
      costs associated with the impacts to the water industry. However, in the case of
      a low uptake, such savings would not be enough to cover the increased costs
      associated with the wastewater provision. As a result, this study highlights the
      need for policy intervention in terms of regulating the use of FWDs, either
      promoting them as an alternative to landfill to increase savings from waste
      management, or banning them as a threat to wastewater operations to reduce
      potential costs to the water industry.

PMID- 22397904
TI  - Prevalence of adults with type 1 diabetes who meet the goals of care in daily
      clinical practice: a nationwide multicenter study in Brazil.
AB  - OBJECTIVE: To determine the prevalence of patients with type 1 diabetes mellitus
      who meet the glycemic and cardiovascular (CV) risk factors goals and the
      frequency of screening for diabetic complications in Brazil according to the
      American Diabetes Association guidelines. RESEARCH DESIGN AND METHODS: This was a
      cross-sectional, multicenter study conducted between December 2008 and December
      2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 1774
      adult patients (56.8% females, 57.2% Caucasians) aged 30.3 +/- 9.8 years with
      diabetes duration of 14.3 +/- 8.8 years. RESULTS: Systolic blood pressure was at
      goal in 40.3% and diastolic blood pressure was at goal in 26.6% of hypertensive
      patients. LDL cholesterol and HbA1c were at the goal in 45.2% and 13.2% of the
      patients, respectively. Overweight was presented in 25.6% and obesity in 6.9%.
      Among those with more than 5 years of disease, screening for retinopathy was
      performed in the preceding year in 70.1%. Nephropathy and feet complications were
      screened in 63.1% and 65.1%, respectively. CONCLUSIONS: The majority of patients
      did not meet metabolic control goals and a substantial proportion was not
      screened for diabetic complications. These issues may increase the risk of
      chronic complications and negatively impact public health.

PMID- 22397905
TI  - Influence of OPRM1 Asn40Asp variant (A118G) on [11C]carfentanil binding
      potential: preliminary findings in human subjects.
AB  - The Asn40Asp variant (A118G) of the MU opioid receptor (OPRM1) gene is thought to
      contribute to the development and treatment of alcohol dependence. Employing
      positron emission tomography (PET), we first examined whether the single
      nucleotide polymorphism (SNP) modifies binding potential (BP(ND)) of the MU
      selective ligand [(11)C]carfentanil in healthy control (Con) and 5-d abstinent
      alcohol-dependent (AD) subjects (unblocked basal scan). Second, we examined
      whether the allelic variants were associated with differences in OPRM1 occupancy
      by naltrexone (50 mg) in AD subjects. Con and AD carriers of the G allele (AG)
      had lower global BP(ND) at the basal scan than subjects homozygous for the A
      allele (AA). In AD subjects, naltrexone occupancy was slightly higher in AG
      subjects (98.9%) compared to AA subjects (93.1%), but this was not significant.
      We are the first to demonstrate using PET in healthy normal and AD subjects that
      the A118G SNP alters OPRM1 availability.

PMID- 22397906
TI  - Nursing teamwork and unit size.
AB  - The aim of this study is to determine the relationship between the team and unit
      size and level of nursing teamwork. The sample for the study was 2,265 direct
      care nursing providers from 53 units in four hospitals. Pearson correlation
      coefficients were calculated to determine if five variables to measure unit size
      (average daily census, number of registered nurses, number of nursing assistants
      [NAs], and number of total staff) correlated with teamwork overall and with five
      teamwork subscales (trust, team orientation, backup, shared mental model, and
      leadership). A significant negative correlation was found between nursing
      teamwork overall and the number of NAs, and average daily census. To optimize
      nursing unit teamwork, consideration needs to be given to strategies to reduce
      the size of nursing teams.

PMID- 22397907
TI  - Influence of emotional distraction on working memory performance in borderline
      personality disorder.
AB  - BACKGROUND: Emotion dysregulation, characterized by heightened emotional arousal
      and increased emotional sensitivity, is a core feature of borderline personality
      disorder (BPD). Although current theories emphasize the disruptive potential of
      negative emotions on cognitive functioning in BPD, behavioral and neurobiological
      data on this relationship are still lacking. METHOD: Using functional magnetic
      resonance imaging (fMRI), neural activity was investigated in 22 unmedicated BPD
      patients and 22 healthy participants (matched for age, education and
      intelligence) performing an adapted Sternberg working memory task, while being
      distracted by emotional (negatively arousing) and neutral pictures from the
      International Affective Picture System (IAPS). RESULTS: Emotional distraction was
      associated with significantly higher activation in the amygdala and decreased
      activation in the dorsolateral prefrontal cortex (DLPFC), extending findings of
      previous studies in healthy individuals. Patients with BPD showed significantly
      longer reaction times (RTs) along with significantly higher activation in the
      amygdala and insula during emotional distraction compared to healthy
      participants, suggesting that they were more distracted by emotional pictures
      during the working memory task. Moreover, in the group of BPD patients, a
      significant negative correlation was found between activation in limbic brain
      regions and self-reports of current dissociative states. CONCLUSIONS: Our
      findings suggest hyper-responsiveness to emotionally distracting pictures in BPD
      patients that negatively affects working memory performance. This stresses the
      importance of emotion dysregulation in the context of cognitive functioning.
      Moreover, our findings suggest that dissociative states have a dampening effect
      on neural reactivity during emotional challenge in BPD.

PMID- 22397908
TI  - What matters most to patients?

PMID- 22397909
TI  - Abnormal functional brain asymmetry in depression: evidence of biologic
      commonality between major depression and dysthymia.
AB  - Prior studies have found abnormalities of functional brain asymmetry in patients
      having a major depressive disorder (MDD). This study aimed to replicate findings
      of reduced right hemisphere advantage for perceiving dichotic complex tones in
      depressed patients, and to determine whether patients having "pure" dysthymia
      show the same abnormality of perceptual asymmetry as MDD. It also examined gender
      differences in lateralization, and the extent to which abnormalities of
      perceptual asymmetry in depressed patients are dependent on gender. Unmedicated
      patients having either a MDD (n=96) or "pure" dysthymic disorder (n=42) and
      healthy controls (n=114) were tested on dichotic fused-words and complex-tone
      tests. Patient and control groups differed in right hemisphere advantage for
      complex tones, but not left hemisphere advantage for words. Reduced right
      hemisphere advantage for tones was equally present in MDD and dysthymia, but was
      more evident among depressed men than depressed women. Also, healthy men had
      greater hemispheric asymmetry than healthy women for both words and tones,
      whereas this gender difference was not seen for depressed patients. Dysthymia and
      MDD share a common abnormality of hemispheric asymmetry for dichotic listening.

PMID- 22397910
TI  - Measuring consistency of autobiographical memory recall in depression.
AB  - Autobiographical amnesia assessments in depression need to account for normal
      changes in consistency over time, contribution of mood and type of memories
      measured. We report herein validation studies of the Columbia Autobiographical
      Memory Interview - Short Form (CAMI-SF), exclusively used in depressed patients
      receiving electroconvulsive therapy (ECT) but without previous published report
      of normative data. The CAMI-SF was administered twice with a 6-month interval to
      44 healthy volunteers to obtain normative data for retrieval consistency of its
      Semantic, Episodic-Extended and Episodic-Specific components and assess their
      reliability and validity. Healthy volunteers showed significant large decreases
      in retrieval consistency on all components. The Semantic and Episodic-Specific
      components demonstrated substantial construct validity. We then assessed CAMI-SF
      retrieval consistencies over a 2-month interval in 30 severely depressed patients
      never treated with ECT compared with healthy controls (n=19). On initial
      assessment, depressed patients produced less episodic-specific memories than
      controls. Both groups showed equivalent amounts of consistency loss over a 2
      month interval on all components. At reassessment, only patients with persisting
      depressive symptoms were distinguishable from controls on episodic-specific
      memories retrieved. Research quantifying retrograde amnesia following ECT for
      depression needs to control for normal loss in consistency over time and
      contribution of persisting depressive symptoms.

PMID- 22397912
TI  - Real-time predictors of suicidal ideation: mobile assessment of hospitalized
      depressed patients.
AB  - Suicidal ideation is a risk factor for suicide attempt and completion. Cross
      sectional or retrospective studies cannot capture the dynamic course and possible
      predictors of suicidal ideation as it occurs in daily life. This study utilizes
      an experience sampling paradigm to identify real-time predictors of suicidal
      ideation in inpatients with major depressive disorder. Thirty-one depressed
      patients admitted to a psychiatric unit were signaled by a mobile device to
      record suicidal ideation, affect, and other symptoms, multiple times a day over 1
      week. Participants completed a total of 1350 questionnaires. Seventy-four percent
      of the sample reported suicidal ideation during the week. Time-lagged analyses
      revealed that momentary ratings of Sadness, Tension, and Boredom (as well as
      suicidal ideation itself) predicted subsequent suicidal thoughts in the following
      hours. Baseline severity of depression and past suicide attempts were both
      correlated with mean ideation severity during the week. A number of predictors
      identified in prior research (e.g. hopelessness) were unrelated to subsequent
      suicidal ideation in the current study. Momentary interventions that guide
      individuals through activities designed to reduce levels of Sadness, Tension, and
      Boredom in real-time (e.g., thought challenging, relaxation, behavioral
      activation) may be especially warranted.

PMID- 22397911
TI  - Behavioral inhibition and PTSD symptoms in veterans.
AB  - Behavioral inhibition (BI), a temperamental bias to respond to novel stimuli with
      avoidance behaviors, is a risk factor for posttraumatic stress disorder (PTSD).
      It is unclear whether BI accounts for additional variance in PTSD symptom
      severity beyond that accounted for by general anxiety. Here, 109 veterans (mean
      age 50.4 years, 9.2% female) provided self-assessment of PTSD symptoms, state and
      trait anxiety, combat exposure, and current (adult) and retrospective (childhood)
      BI. Adult BI was correlated with anxiety and PTSD symptom severity, especially
      cluster C (avoidance) symptoms, but not with combat exposure. A regression model
      including adult BI, state and trait anxiety, and combat exposure was able to
      correctly classify over 80% of participants according to presence or absence of
      severe PTSD symptoms. Because avoidance behaviors are a core component of PTSD,
      self-assessments of BI may be an important tool in understanding PTSD and
      potentially assessing vulnerability to the disorder.

PMID- 22397913
TI  - Decreased suicidal ideation in depressed patients with or without comorbid
      posttraumatic stress disorder treated with selective serotonin reuptake
      inhibitors: an open study.
AB  - Comorbidity of posttraumatic stress disorder (PTSD) and major depressive disorder
      (MDD) is associated with higher morbidity including suicidal ideation and
      behavior. Selective serotonin reuptake inhibitors (SSRIs) are a known treatment
      for PTSD, MDD and comorbid PTSD and MDD. Since the patients with comorbid MDD and
      PTSD (PTSD-MDD) are sicker, we hypothesize a poorer response to treatment
      compared to patients with MDD only. Ninety-six MDD patients were included in the
      study: 76 with MDD only and 20 with PTSD-MDD. Demographic and clinical parameters
      at baseline were assessed. We examined clinical parameters before and after 3
      months of open SSRI treatment in subjects with PTSD-MDD and compared this group
      to individuals with MDD only. At baseline, PTSD-MDD patients had higher Hamilton
      Depression Rating Scale and Buss-Durkee Hostility Scale scores compared with MDD
      only subjects. There was a significant decrease in scores on the Hamilton
      Depression Rating Scale, Beck Depression Inventory, Beck Hopelessness Scale, and
      Beck Scale for Suicidal Ideation after 3 months of treatment with SSRIs in both
      groups. The magnitude of improvement in Beck Scale for Suicidal Ideation scores
      was greater in the PTSD-MDD group compared to the MDD only subjects. Symptoms of
      depression including suicidal ideation improved in MDD patients with or without
      comorbid PTSD after 3 months of treatment with SSRIs but improvement in suicidal
      ideation was greater in the PTSD-MDD group. Our finding has not supported the
      hypothesis that a response to treatment is poorer in the PTSD-MDD group which may
      indicate that sicker patients benefit more from the treatment.

PMID- 22397914
TI  - Personality traits, cognition and volumetric MRI changes in elderly patients with
      early-onset depression: a 2-year follow-up study.
AB  - Previous studies revealed personality changes in elderly patients with early
      onset depression (EOD) that persist in euthymic stages. However, depression in
      older patients is a complex disorder that may affect not only personality, but
      also cognition and brain structure. To address this issue, a cross-sectional
      comparison and 2-year follow-up of 28 EOD elderly patients and 48 healthy
      controls included detailed neurocognitive assessment, estimates of brain volumes
      in limbic areas and white matter hyperintensities, as well as evaluation of the
      Five Factor Model of personality, in a remitted mood state. Results revealed that
      cognitive performances as well as brain volumes were preserved in EOD patients
      both at baseline and at follow-up. The increased Neuroticism factor and Anxiety
      facet scores as well as the decreased Warmth and Positive Emotions facet scores
      found at baseline reached the level of healthy controls after 2 years. Only the
      Depression facet scores remained significantly higher in EOD patients compared to
      controls upon follow-up. Results were independent of depressive relapse since
      baseline (25% of patients). These findings suggest that both cognitive
      performances and brain volumes show long-term preservation in older EOD patients.
      In contrast, the depression-related personality facet might be a trait like
      marker that persists in the long-term evolution of this disorder.

PMID- 22397915
TI  - Patterns of serotonergic antidepressant usage in prodromal Huntington disease.
AB  - Antidepressant usage in prodromal Huntington Disease (HD) remains
      uncharacterized, despite its relevance in designing experiments, studying
      outcomes of HD, and evaluating the efficacy of therapeutic interventions. We
      searched baseline medication logs of 787 prodromal HD and 215 healthy comparison
      (HC) participants for antidepressant use. Descriptive and mixed-effects logistic
      regression modeling characterized usage across participants. At baseline,
      approximately one in five prodromal HD participants took antidepressants. Of
      those, the vast majority took serotonergic antidepressants (selective serotonin
      reuptake inhibitor (SSRI) or serotonin/norepinephrine reuptake inhibitor (SNRI)).
      Significantly more prodromal HD participants used serotonergic antidepressants
      than their HC counterparts. Because of the prevalence of these medications,
      further analyses focused on this group alone. Mixed-effects logistic regression
      modeling revealed significant relationships of both closer proximity to diagnosis
      and female sex with greater likelihood to be prescribed a serotonergic
      antidepressant. More prodromal HD participants took antidepressants in general
      and specifically the subclass of serotonergic antidepressants than their at-risk
      counterparts, particularly when they were closer to predicted time of conversion
      to manifest HD. These propensities must be considered in studies of prodromal HD
      participants.

PMID- 22397916
TI  - Sex differences on emotional processing are modulated by subclinical levels of
      alexithymia and depression: a preliminary assessment using event-related
      potentials.
AB  - Several studies have suggested that women are more sensitive than men to emotions
      in general. Event-related potential (ERP) studies have demonstrated N2 and P3b
      modulations, suggesting that women allocate more attentional resources to
      emotions than men do. However, the exact origin of this emotional modulation by
      sex is still a matter of debate. We wondered whether these sex differences might
      be due to some specific personality traits of women and men. Thirty participants
      (15 males and 15 females) were selected so that there were no sex differences on
      alexithymia, or depression and anxiety scales. The participants were asked to
      complete a "modified emotional" oddball task, in which they had to detect deviant
      stimuli among frequent neutral ones as quickly as possible. Behavioral
      performance, N2 and P3b ERP data were analyzed. When personality factors were
      controlled for, the sex differences on N2 and P3b components of the ERPs
      disappeared. Moreover, linear regression analyses showed that alexithymia was
      much better than sex at predicting the N2 latencies, while depression was the
      best factor for predicting the P3b latency. These results suggest that
      personality factors should be taken into account when sex differences on
      emotional processing are investigated.

PMID- 22397917
TI  - Social cognition disorders in military police officers affected by posttraumatic
      stress disorder after the attack of An-Nasiriyah in Iraq 2006.
AB  - Emotional numbness in individuals affected by posttraumatic stress disorder
      (PTSD) may be a result of the depletion of emotional capacities. The ability to
      process emotions in a social context is a part of social cognition, which is
      still an under-explored topic in PTSD. The present study investigated deficits in
      social cognition, such as emotion recognition and theory of mind, and their
      relationship to emotional numbing in 35 military police officers who were in Iraq
      in April 2006 during a terrorist attack in An-Nasiriyah. Our results indicated
      that individuals suffering from PTSD showed deficits in social cognition when
      compared with healthy subjects. These disorders seemed to involve emotional
      numbing rather than clinical symptoms such as anxiety and depression. Future
      research directions are suggested to improve the measurement of emotional
      functioning in PTSD.

PMID- 22397918
TI  - Personality traits and schizophrenia: evidence from a case-control study and meta
      analysis.
AB  - Personality is considered to be an important aspect of schizophrenia, primarily
      because it may influence patients' symptoms and social functioning. Specific
      personality traits are related to schizophrenia. The Temperament and Character
      Inventory (TCI) measures four traits of temperament - novelty seeking (NS), harm
      avoidance (HA), reward dependence (RD) and persistence (PS) - and three traits of
      character - self-directedness (SD), cooperativeness (CO) and self-transcendence
      (ST). We investigated associations between schizophrenia and personality traits
      using the TCI in a Japanese case-control sample (99 patients and 179 controls).
      Patients with schizophrenia scored higher on HA and ST and lower on NS, RD, SD
      and CO compared with controls in our case-control sample. We then performed a
      meta-analysis of samples from the published literature and our sample (384
      patients and 656 controls). We found no evidence of heterogeneity among studies,
      except for NS in the overall population. Possible associations between
      personality traits (HA, RD, PS, SD, CO and ST) and schizophrenia were revealed.
      The effect sizes (Hedges' g) of the temperament traits were 0.98 for HA, -0.43
      for RD and -0.23 for PS, and those of the character traits were -0.96 for SD, 
      0.47 for CO and 0.61 for ST. These findings suggest that patients with
      schizophrenia have a unique temperament and character profile compared with the
      general population.

PMID- 22397919
TI  - Salivary cortisol, heart rate, electrodermal activity and subjective stress
      responses to the Mannheim Multicomponent Stress Test (MMST).
AB  - The availability of effective laboratory paradigms for inducing psychological
      stress is an important requirement for experimental stress research. Reliable
      protocols are scarce, usually laborious and manpower-intensive. In order to
      develop an economical, easily applicable standardized stress protocol, we have
      recently tailored the Mannheim Multicomponent Stress Test (MMST). This test has
      been shown to induce relatively high stress responses without focusing on social
      evaluative components. In this study we evaluated changes in electrodermal
      activity and salivary cortisol in response to the MMST. The MMST simultaneously
      combines cognitive (mental arithmetic), emotional (affective pictures), acoustic
      (white noise) and motivational stressors (loss of money). This study comprised
      two independent experiments. For experiment 1, 80 female subjects were recruited;
      30 subjects (15 females) participated in experiment 2. Significant changes in
      electrodermal activity and salivary cortisol levels in response to MMST exposure
      were found. Subjective stress and heart rate responses were significantly
      increased in both experiments. These results indicate that the MMST is an
      economical stress paradigm which is also applicable in larger cohorts or
      multicenter studies for investigating stress reactions. As social-evaluative
      threat is not the main stress component of the MMST, this procedure represents a
      useful and complementary alternative to other established stress protocols.

PMID- 22397920
TI  - Stability of sex differences by diagnosis in psychiatric hospitalizations.
AB  - We examined sex differences in the distribution of psychiatric diagnoses among
      hospitalized patients, controlling for socio-demographic variables. The sample
      included 1865 psychiatric inpatients consecutively admitted during a 9-year
      period. The finding of a higher proportion of men among patients hospitalized for
      schizophrenia or substance use disorder and a higher proportion of women among
      those admitted for affective disorders, including bipolar disorder, was stable
      over time. A better understanding of these differences may help to establish more
      effective treatment strategies.

PMID- 22397921
TI  - Differential age- and disease-related effects on the expression of genes related
      to the arachidonic acid signaling pathway in schizophrenia.
AB  - We have previously identified differential effects of age on global brain gene
      expression profiles in subjects with schizophrenia compared to normal controls.
      Here, we have focused on age-related effects of genes associated with the
      arachidonic acid-related inflammation pathway. Linear correlation analysis of
      published microarray expression data reveal strong age- and cell-type- specific
      effects on the expression of genes related to the arachidonic acid signaling
      pathway, which differed in control subjects compared to those with schizophrenia.
      Using real-time qPCR analysis, we validated age and disease effects of
      arachidonic acid-related genes in a large cohort of subjects with schizophrenia
      and matched controls (n=76 subjects in total). We found that levels of
      prostaglandin-endoperoxide synthase 1 (PTGS1; aka COX-1) and prostaglandin
      endoperoxide receptor 3 (PTGER3) mRNA are increased, and levels of prostaglandin
      endoperoxide synthase 2 (PTGS2; aka COX-2) mRNA are decreased, in older subjects
      with schizophrenia (> 40years of age) compared to matched normal controls or
      younger subjects with schizophrenia (< 40years of age). These findings contribute
      to the accumulating evidence suggesting that inflammatory processes in the CNS
      contribute to pathophysiology of schizophrenia and further suggest that age may
      be an important factor in the potential use of anti-inflammatory therapies.

PMID- 22397922
TI  - Synthesis and characterization of pH-responsive and folated nanoparticles based
      on self-assembled brush-like PLGA/PEG/AEMA copolymer with targeted cancer therapy
      properties: A comprehensive kinetic study.
AB  - In this study, a novel nanocarrier was synthesized based on methacrylated
      poly(lactic-co-glycolic acid) (mPLGA) as a lipophilic domain, acrylated methoxy
      poly(ethylene glycol) (aMPEG) as hydrophilic part and N-2-[(tert
      butoxycarbonyl)amino] ethyl methacrylamide (Boc-AEMA) as pH-responsive segment.
      Radical polymerization of the above-mentioned three modified monomers produces
      amphiphilic brush-like copolymer. The protecting amine group (Boc) was
      selectively deprotected and the latter targeted copolymer was produced through
      the reaction of this copolymer with activated folic acid. Nanoprecipitation
      method was used to prepare quercetin-loaded nanoparticles. Dynamic light
      scattering (DLS) analysis showed that the produced nanoparticles had nanometric
      size (<100nm) and low polydispersity in size at different pHs. Higuchi and
      Korsmeyer-Peppas models were applied to evaluate release mechanisms and kinetics.
      Based on in-vitro degradation study, we found that the brush-like copolymer
      underwent a rapid weight loss in acidic pH.

PMID- 22397923
TI  - Evaluation of DNA binding, antioxidant and cytotoxic activity of mononuclear
      Co(III) complexes of 2-oxo-1,2-dihydrobenzo[h]quinoline-3-carbaldehyde
      thiosemicarbazones.
AB  - Four new 2-oxo-1,2-dihydrobenzo[h]quinoline-3-carbaldehyde N-substituted
      thiosemicarbazone ligands (H(2)-LR, where R = H, Me, Et or Ph) and their
      corresponding new cobalt(III) complexes have been synthesized and characterized.
      The structures of the complexes 2 and 3 were determined by single crystal X-ray
      diffraction analysis. The interactions of the new complexes with DNA were
      investigated by absorption, emission and viscosity studies which indicated that
      the complexes bind to DNA via intercalation. Antioxidant studies of the new
      complexes showed that the significant antioxidant activity against DPPH radical.
      In addition, the in vitro cytotoxicity of complexes 1-4 against A549 cell line
      was assayed which showed higher cytotoxic activity with lower IC(50) values
      indicating their efficiency in killing the cancer cells even at very low
      concentrations.

PMID- 22397924
TI  - 99mTc(I)/Re(I) tricarbonyl complexes for in vivo targeting of melanotic melanoma:
      Synthesis and biological evaluation.
AB  - The (99m)Tc (I) tricarbonyl complexes fac-[(99m)Tc(kappa(3)-L)(CO)(3)] (Tc1-Tc6)
      containing N-ethylpyrrolidine and N,N-diethylethylamine groups for melanin
      binding, were evaluated in vitro and in vivo as radioactive probes for the
      targeting of melanotic melanoma. Aiming at the modification of their size,
      topology and lipophilicity, Tc1-Tc6 were obtained based on an S,N,O-donor
      bifunctional chelator (BFC) derived from cysteamine and on pyridyl- and pyrazolyl
      containing N,N,O-donor BFCs. Tc1-Tc6 were chemically identified by HPLC
      comparison with the Re congeners (Re1-Re6) that were synthesized at the
      macroscopic level and fully characterized by common analytical techniques. With
      the exception of Tc5 and Tc6, these (99m)Tc complexes are moderately lipophilic,
      and bind to melanin with moderate to high affinity (23-87%). The cell uptake of
      Tc1-Tc6, expressed as a percentage of total activity per million cells, spanned
      between 0.86 and 21.02% for the melanotic B16-F1 cell line and between 0.49% and
      13.58% for the amelanotic A375 cell line. In the B16-F1 cell line, Tc1, Tc3 and
      Tc4 showed moderate cellular uptake values (>10% at 4 h of incubation). In the
      amelanotic A375 cell line, only Tc4 has shown a moderate cell uptake (>10% at 4 h
      of incubation), with all the other compounds displaying a relatively poor uptake,
      i.e. inferior to 5%. Competition studies with haloperidol have shown that the
      involvement of sigma receptors in cellular uptake and retention is likely to
      occur for Tc4. Complex Tc1, stabilized with the S,N,O-donor BFC and containing a
      N,N-diethylethylamine group, presented the most promising biological profile for
      in vivo targeting of melanoma, showing a moderate tumor uptake of 2.17% ID/g at 1
      h p.i in a B16-F1 melanoma-bearing mouse and rather favorable target/non-target
      ratios with values as high as 16.9 and 5.2 for tumor/muscle and tumor/blood
      ratios, respectively.

PMID- 22397925
TI  - Disruption of cyclooxygenase-2 prevents downregulation of cortical AQP2 and AQP3
      in response to bilateral ureteral obstruction in the mouse.
AB  - Bilateral ureteral obstruction (BUO) in rats is associated with increased
      cyclooxygenase type 2 (COX-2) expression, and selective COX-2 inhibition prevents
      downregulation of aquaporins (AQPs) in response to BUO. It was hypothesized that
      a murine model would display similar changes in renal COX-2 and AQPs upon BUO and
      that targeted disruption of COX-2 protects against BUO-induced suppression of
      collecting duct AQPs. COX-2(-/-) and wild-type littermates (C57BL/6) were
      employed to determine COX-1, -2, AQP2, and AQP3 protein abundances and
      localization after BUO. In a separate series, sham and BUO wild-type mice were
      treated with a selective COX-2 inhibitor, parecoxib. The COX-2 protein level
      increased in wild-type mice in response to BUO and was not detectable in COX-2(-/
      ). COX-1 protein abundance was increased in sham-operated and BUO mice. Total
      AQP2 and -3 mRNA and protein levels decreased significantly after BUO in the
      cortex+outer medulla (C+OM) and inner medulla (IM). The decrease in C+OM AQP2 and
      -3 levels was attenuated/prevented in COX-2(-/-) mice, whereas there was no
      change in the IM. In parallel, inhibition of COX-2 by parecoxib rescued C+OM AQP3
      and IM AQP2 protein level in wild-type mice subjected to BUO. In summary, 1) In
      C57BL/6 mice, ureteral obstruction increases renal COX-2 expression in
      interstitial cells and lowers AQP2/-3 abundance and 2) inhibition of COX-2
      activity by targeted disruption or pharmacological blockade attenuates
      obstruction-induced AQP downregulation. In conclusion, COX-2-derived
      prostaglandins contribute to downregulation of transcellular water transporters
      in the collecting duct and likely to postobstruction diureses in the mouse.

PMID- 22397927
TI  - Dedicated phantom materials for spectral radiography and CT.
AB  - As x-ray imaging technology moves from conventional radiography and computed
      tomography (CT) to spectral radiography and CT, dedicated phantom materials are
      needed for spectral imaging. The spectral phantom materials should accurately
      represent the energy-dependent mass-attenuation coefficients of different types
      of tissues. Although tissue-equivalent phantom materials were previously
      developed for CT and radiation therapy applications, these materials are
      suboptimal for spectral radiography and CT; they are not compatible with contrast
      agents, do not represent many of the tissue types and do not provide accurate
      values of attenuation characteristics of tissue. This work provides theoretical
      framework and a practical method for developing tissue-equivalent spectral
      phantom materials with a required set of parameters. The samples of the tissue
      equivalent spectral phantom materials were developed, tested and characterized.
      The spectral phantom materials were mixed with iodine, gold and calcium contrast
      agents and evaluated. The materials were characterized by CT imaging and x-ray
      transmission experiments. The fabricated materials had nearly identical
      densities, mass attenuation coefficients, effective atomic numbers and electron
      densities as compared to corresponding tissue materials presented in the ICRU-44
      report. The experimental results have shown good volume uniformity and inter
      sample uniformity (repeatability of sample fabrication) of the fabricated
      materials. The spectral phantom materials were fabricated under laboratory
      conditions from readily available and inexpensive components. It was concluded
      that the presented theoretical framework and fabrication method of dedicated
      spectral phantom materials could be useful for researchers and developers working
      in the new area of spectral radiography and CT. Independently, the results could
      also be useful for other applications, such as radiation therapy.

PMID- 22397926
TI  - Novel role of NF-kappaB-p65 in antioxidant homeostasis in human kidney-2 cells.
AB  - Nuclear factor-kappaB (NF-kappaB) plays a role in inflammation. However, we
      recently reported an association between NF-kappaB and antioxidant enzymes in
      renal proximal tubules of exercise-trained rats, suggesting its role in
      antioxidant homeostasis (George L, Lokhandwala MF, Asghar M. Am J Physiol Renal
      Physiol 297: F1174-F1180, 2009). A direct role of NF-kappaB in antioxidant
      homeostasis in renal cells has not been elucidated and warrants investigation.
      Therefore, we examined whether NF-kappaB has a direct role in antioxidant
      homeostasis and redox balance in human kidney-2 cells overexpressing NF-kappaB
      p65 and compared them with the cells overexpressing Nrf-2, a well-known
      transcription factor involved in antioxidant homeostasis. The ability of NF
      kappaB-p65 to increase antioxidant enzymes, to reduce reactive oxygen species
      (ROS), and to rescue ROS-induced renal dopamine D1 receptor dysfunction, was
      studied. The transcription activity of NF-kappaB-p65 and Nrf-2, measured as
      luciferase reporter activity, increased in cells overexpressing these nuclear
      factors. The levels of mRNA and activity of glutathione peroxidase as well as the
      protein levels of superoxide dismutase-1 and glutamylcystein transferase were
      increased in cells overexpressing NF-kappaB-p65 and Nrf-2. Furthermore, the
      levels of ROS decreased and D1 receptor agonist SKF38393-mediated
      [(35)S]GTPgammaS binding (index of D1 receptor function) increased in the
      presence of hydrogen peroxide in cells overexpressing NF-kappaB-p65 and Nrf-2.
      These results suggest a direct role of NF-kappaB-p65 in antioxidant homeostasis,
      contributing to redox balance in renal cells.

PMID- 22397928
TI  - Identification of genes contributing to the intracellular replication of Brucella
      abortus within HeLa and RAW 264.7 cells.
AB  - Brucella abortus, the causative agent of brucellosis, can survive and replicate
      within host cells. Understanding bacterial virulence factors and bacteria-host
      cell interactions is critical for controlling brucellosis, yet very little is
      known about the virulence strategies and signaling pathways activated in
      phagocytes during infection to ensure their growth and survival. B. abortus was
      mutagenized by mini-Tn5Km2 transposon mutagenesis to identify virulence genes
      related to the internalization and intracellular replication of the bacteria. Of
      the total 2300 mutants used to infect HeLa cells, 23 mutants defective for
      intercellular growth and the mutated genes were identified. Sequence analysis of
      DNA flanking the transposon showed various insertion sites in bacterial genes
      that might be associated with virulence, including genes associated with
      lipoproteins, amino acid metabolism, translation, transcription, carbohydrate
      transport, coenzyme transport, inorganic ion transport, energy metabolism,
      membrane transport, and cell wall/membrane biogenesis. Moreover, mutants were
      classified into class I, class II and class III as higher, similar, and lower
      internalization, respectively, into HeLa cells. Furthermore, defective mutants
      for intracellular growth in HeLa cells were found to be defective in RAW 264.7
      cells. Taken together, we suggest that the identified virulence associated genes
      might contribute to the intracellular growth and survival of B. abortus in
      phagocytes.

PMID- 22397929
TI  - Resistance to phenicol compounds following adaptation to quaternary ammonium
      compounds in Escherichia coli.
AB  - Bacterial adaptation to quaternary ammonium compounds (QACs) is mainly documented
      for benzalkonium chloride (BC) and few data are available for other QACs. The aim
      of this study was to assess the effects of repeated exposure to different
      quaternary ammonium compounds (QACs) on the susceptibility and/or resistance of
      bacteria to other QACs and antibiotics. Escherichia coli strains (n=10) were
      adapted by daily exposure to increasingly sub-inhibitory concentrations of a QAC
      for 7 days. Three QACs were studied. Following adaptation, we found similar
      levels of reduction in susceptibility to QACs with a mean 3-fold increase in the
      minimum inhibitory concentration (MIC) compared to initial MIC values, whatever
      the QAC used during adaptation. No significant differences in antibiotic
      susceptibility were observed between the tested QACs. Antibiotic susceptibility
      was reduced from 3.5- to 7.5-fold for phenicol compounds, beta lactams, and
      quinolones. Increased MIC was associated with a shift in phenotype from
      susceptible to resistant for phenicol compounds (florfenicol and chloramphenicol)
      in 90% of E. coli strains. Regardless of the QAC used for adaptation, exposure to
      gradually increasing concentrations of this type of disinfectant results in
      reduced susceptibility to QACs and antibiotics as well as cross-resistance to
      phenicol compounds in E. coli strains. Extensive use of QACs at sub-inhibitory
      concentrations may lead to the emergence of antibiotic-resistant bacteria and may
      represent a public health risk.

PMID- 22397930
TI  - Initial sequence characterization of the rhabdoviruses of squamate reptiles,
      including a novel rhabdovirus from a caiman lizard (Dracaena guianensis).
AB  - Rhabdoviruses infect a variety of hosts, including non-avian reptiles. Consensus
      PCR techniques were used to obtain partial RNA-dependent RNA polymerase gene
      sequence from five rhabdoviruses of South American lizards; Marco, Chaco, Timbo,
      Sena Madureira, and a rhabdovirus from a caiman lizard (Dracaena guianensis). The
      caiman lizard rhabdovirus formed inclusions in erythrocytes, which may be a route
      for infecting hematophagous insects. This is the first information on behavior of
      a rhabdovirus in squamates. We also obtained sequence from two rhabdoviruses of
      Australian lizards, confirming previous Charleville virus sequence and finding
      that, unlike a previous sequence report but in agreement with serologic reports,
      Almpiwar virus is clearly distinct from Charleville virus. Bayesian and maximum
      likelihood phylogenetic analysis revealed that most known rhabdoviruses of
      squamates cluster in the Almpiwar subgroup. The exception is Marco virus, which
      is found in the Hart Park group.

PMID- 22397931
TI  - Comparative evaluation of live marker vaccine candidates "CP7_E2alf" and "flc11"
      along with C-strain "Riems" after oral vaccination.
AB  - Due to the tremendous socio-economic impact of classical swine fever (CSF)
      outbreaks, emergency vaccination scenarios are continuously under discussion.
      Unfortunately, all currently available vaccines show restrictions either in terms
      of marker capacities or immunogenicity. Recent research efforts were therefore
      directed at the design of new modified live marker vaccines. Among the most
      promising candidates the chimeric pestiviruses "CP7_E2alf" and "flc11" were
      identified. Within an international research project, these candidates were
      comparatively tested in challenge experiments after a single oral vaccination.
      Challenge infection was carried out with highly virulent CSF virus strain
      "Koslov", 14 or 21 days post vaccination (dpv), respectively. Safety, efficacy,
      and marker potential were addressed. All assessments were done in comparison with
      the conventional "gold standard" C-strain "Riems" vaccine. In addition to the
      challenge trials, multiple vaccinations with both candidates were performed to
      further assess their marker vaccine potential. All vaccines were safe and yielded
      full protection upon challenge 21 days post vaccination. Neither serological nor
      virological investigations showed major differences among the three vaccines.
      Whereas CP7_E2alf also provided clinical protection upon challenge at 14 days
      post vaccination, only 50% of animals vaccinated with flc11, and 83% vaccinated
      with C-strain "Riems" survived challenge at this time point. No marked
      differences were seen in protected animals. Despite the fact that all multiple
      vaccinated animals stayed sero-negative in the accompanying marker test, the
      discriminatory assay remains a weak point due to delayed or inexistent detection
      of some of the vaccinated and subsequently infected animals. Nevertheless, the
      potential as live marker vaccines could be confirmed for both vaccine candidates.
      Future efforts will therefore be directed at the licensing of "Cp7_E2alf" as the
      first live marker vaccine for CSF.

PMID- 22397932
TI  - Identification of swine H1N2/pandemic H1N1 reassortant influenza virus in pigs,
      United States.
AB  - In October and November 2010, novel H1N2 reassortant influenza viruses were
      identified from pigs showing mild respiratory signs that included cough and
      depression. Sequence and phylogenetic analysis showed that the novel H1N2
      reassortants possesses HA and NA genes derived from recent H1N2 swine isolates
      similar to those isolated from Midwest. Compared to the majority of reported
      reassortants, both viruses preserved human-like host restrictive and putative
      antigenic sites in their HA and NA genes. The four internal genes, PB2, PB1, PA,
      and NS were similar to the contemporary swine triple reassortant viruses'
      internal genes (TRIG). Interestingly, NP and M genes of the novel reassortants
      were derived from the 2009 pandemic H1N1. The NP and M proteins of the two
      isolates demonstrated one (E16G) and four (G34A, D53E, I109T, and V313I) amino
      acid changes in the M2 and NP proteins, respectively. Similar amino acid changes
      were also noticed upon incorporation of the 2009 pandemic H1N1 NP in other
      reassortant viruses reported in the U.S. Thus the role of those amino acids in
      relation to host adaptation need to be further investigated. The reassortments of
      pandemic H1N1 with swine influenza viruses and the potential of interspecies
      transmission of these reassortants from swine to other species including human
      indicate the importance of systematic surveillance of swine population to
      determine the origin, the prevalence of similar reassortants in the U.S. and
      their impact on both swine production and public health.

PMID- 22397933
TI  - Genetic and pathobiologic characterization of H3N2 canine influenza viruses
      isolated in the Jiangsu Province of China in 2009-2010.
AB  - The newly emerging canine influenza virus (CIV) causes considerable concerns for
      both veterinary and public health. During 2009-2010, six strains of H3N2
      influenza virus were isolated from dogs in Jiangsu Province, China. Sequence and
      phylogenetic analysis of eight gene segments revealed that the six viruses were
      most similar to a recent canine-derived subtype H3N2 influenza virus isolated in
      cats from South Korea, which originated from avian strain. By comparing the
      deduced amino acid sequences of the hemagglutinin 1 (HA1) and neuraminidase (NA)
      genes of the six Jiangsu isolates against the most similar avian strains, we
      found that all isolates had several common mutations at the receptor-binding
      sites, potential glycosylation sites and cleavage site in HA1, and antigenic
      sites in both the HA1 and NA segments. Significantly, a unique two amino acid
      insertion in the NA stalk was found. Experimental infection of BALB/c mice
      revealed that viral RNA could be detected in the major rodent organs, such as
      brain, heart, spleen, kidney, liver and intestine, as well as the lung. All the
      sampled organs from infected mice showed significant lesions and viral antigen
      staining. This study highlights the potential of domesticated animals to become a
      reservoir for influenza virus and the need for surveillance programs to detect
      cross-species transmission.

PMID- 22397934
TI  - Enhanced susceptibility of channel catfish to the bacterium Edwardsiella ictaluri
      after parasitism by Ichthyophthirius multifiliis.
AB  - Bacterium Edwardsiella ictaluri and parasite Ichthyophthirius multifiliis (Ich)
      are two common pathogens of cultured fish. The objective of this study was to
      evaluate the susceptibility of channel catfish Ictalurus punctatus to E. ictaluri
      and determine bacterial loads in different fish organs after parasitism by Ich.
      Fish received the following treatments: (1) infected by I. multifiliis at 5000
      theronts/fish and exposed to E. ictaluri; (2) infected by I. multifiliis alone;
      (3) exposed to E. ictaluri alone; and (4) non-infected control. E. ictaluri in
      fish organs were quantified by quantitative real-time polymerase chain reaction
      and reported as genome equivalents per mg of tissue (GEs/mg). The results
      demonstrated that the Ich-parasitized catfish showed significantly (P<0.05)
      higher mortality (91.7%) when exposed to E. ictaluri than non-parasitized fish
      (10%). The bacterial loads in fish infected by 5000 theronts/fish ranged from
      6497 to 163,898 GEs/mg which was between 40 and 2000 fold higher than non
      parasitized fish (49-141 GEs/mg). Ich infection enhanced the susceptibility of
      channel catfish to bacterial invasion and increased fish mortality.

PMID- 22397935
TI  - Enhanced expression of TGFbeta protein in lymphoid organs and lung, but not in
      serum, of pigs infected with a European field isolate of porcine reproductive and
      respiratory syndrome virus.
AB  - Transforming growth factor beta (TGFbeta) is an immunomodulatory cytokine which
      is able to modulate the host immune response eliciting an inefficient response
      against pathogens. In this sense, the role of this cytokine in porcine
      reproductive and respiratory syndrome (PRRS) has been poorly studied and the
      reported results are contradictory. Thus, in the present study, the expression of
      TGFbeta was analysed both at tissue (lymphoid organs and lung) and serum level to
      study its correlation with the expression of PRRS virus (PRRSV). To carry out
      this study, 32 pigs were inoculated with the European PRRSV field isolate 2982
      and sequentially killed from 0 dpi to the end of the study (24 dpi). Blood and
      tissue samples were collected to determine the expression of PRRSV and TGFbeta.
      PRRSV was detected in inoculated animals from 3 dpi until the end of the study,
      however TGFbeta was not detected in sera from inoculated animals. Contrary, an
      increase of TGFbeta antigen was observed both in the lymphoid organs and in the
      lung of PRRSV-inoculated pigs when compared with control group. Since TGFbeta
      play a role as an immunomodulatory cytokine of the immune response and also in
      the differentiation of regulatory T cells (Tregs), the upregulation of the
      TGFbeta at tissue level may play a role in the impairment of the host immune
      response observed during PRRS, being observed a significant correlation between
      PRRSV and TGFbeta expression at lung level.

PMID- 22397936
TI  - EcPV2 DNA in equine genital squamous cell carcinomas and normal genital mucosa.
AB  - Squamous cell carcinoma (SCC) represents the most common genital malignant tumor
      in horses. Similar to humans, papillomaviruses (PVs) have been proposed as
      etiological agents and recently Equine papillomavirus type 2 (EcPV2) has been
      identified in a subset of genital SCCs. The goals of this study were (1) to
      determine the prevalence of EcPV2 DNA in tissue samples from equine genital SCCs,
      penile intraepithelial neoplasia (PIN) and penile papillomas, using EcPV2
      specific PCR, (2) to examine the prevalence of latent EcPV2 infection in healthy
      genital mucosa and (3) to determine genetic variability within EcPV2 and to
      disentangle phylogenetic relationships of EcPV2 among PVs. EcPV2 DNA was detected
      in all but one penile SCC (15/16), in all PIN lesions (8/8) and penile papillomas
      (4/4). Additionally, EcPV2 DNA was demonstrated in one of two metastasized lymph
      nodes, one contact metastasis in the mouth, two vaginal and one anal lesion. In
      healthy horses, EcPV2 DNA was detected in 10% (4/39) of penile swabs but in none
      of vulvovaginal swabs (0/20). This study confirms the presence of EcPV2 DNA in
      equine genital SCCs and shows its involvement in anal lesions, a lymph node and
      contact metastases. Latent EcPV2 presence was also shown in normal male genital
      mucosa. We found that different EcPV2 variants cocirculate among horses and that
      EcPV2 is related to the Delta+Zeta PVs and is only a very distant relative of
      high-risk human PVs causing genital cancer. Thus, similar viral tropism and
      similar malignant outcome of the infection do not imply close evolutionary
      relationship.

PMID- 22397937
TI  - Optimization of an antibiotic sensitivity assay for Mycoplasma hyosynoviae and
      susceptibility profiles of field isolates from 1997 to 2011.
AB  - Mycoplasma hyosynoviae is a common agent responsible for polyarthritis leading to
      decreased production in swine herds worldwide. Antimicrobial agents are used to
      combat infections; however breakpoints for M. hyosynoviae have not yet been
      established. A number of methods have previously been utilized to analyze minimum
      inhibitory concentrations (MICs) for antibiotics against M. hyosynoviae; however
      these techniques as currently described are not easily standardized between
      laboratories. A dry microbroth dilution method was conducted to compare the
      minimum inhibitory concentrations (MICs) for 18 antibiotics, representative of
      different classes, against 24 recent isolates (23 field isolates and the type
      strain) of M. hyosynoviae. The MICs were determined using standard, commercially
      available 96-well Sensititre((r)) plates containing various freeze-dried
      antibiotics at a range of concentrations appropriate to their potency.
      Clindamycin (CLI), a lincosamide antibiotic, showed the highest activity and most
      consistent inhibition for all isolates with an MIC(50) of <= 0.12 MUg/ml.
      Tiamulin (TIA), a pleuromutilin derivative, exhibited an MIC(50) of <= 0.25
      MUg/ml. The isolates had similar levels of susceptibility to the quinolones,
      enrofloxacin (ENRO) and danofloxacin (DANO), exhibiting an MIC(50) of 0.25 MUg/ml
      and 0.5 MUg/ml, respectively. For the macrolides, the MIC(50) for tylosin (TYLT)
      and tilmicosin (TIL) was <= 0.25 MUg/ml and <= 2 MUg/ml respectively, but was <=
      16 MUg/ml for tulathromycin (TUL). For the aminoglycosides, the MIC(50) for
      gentamicin (GEN) was <= 0.5 MUg/ml, while spectinomycin (SPE) and neomycin (NEO)
      had an MIC(50) of <= 4 MUg/ml. The tetracyclines, oxytetracycline (OXY) and
      chlortetracycline (CTET) both had an MIC(50) of <= 2 MUg/ml. Florfenicol (FFN)
      exhibited a MIC(50) of <= 1 MUg/ml. All isolates were resistant to penicillin
      (PEN), ampicillin (AMP), ceftiofur (TIO), trimethoprim/sulfamethoxazole (SXT),
      and sulphadimethoxine (SDM) at all concentrations. Within the isolates tested,
      there was a range of sensitivity detected, with some isolates being overall more
      resistant while others appeared more susceptible. Further research is required to
      demonstrate how this MIC data correlates to clinical efficacy of the various
      antibiotics in the field.

PMID- 22397938
TI  - Molecular epidemiology of foot-and-mouth disease virus type A in South America.
AB  - A databank of 78 VP(1) complete sequences of type A foot-and-mouth disease virus
      (FMDV) from South American isolates was constructed. Forty-nine samples
      corresponded to FMDV that circulated between the years 1999-2008, mainly in
      Venezuela, where most type A outbreaks have occurred lately and twenty-nine to
      strains historically relevant for the continent. The phylogenetic analysis showed
      that all South American FMDV belonged to the Euro-SA topotype. Sixteen
      subgenotypes could be identified, based on a 15% nucleotide divergence cut-off
      criterion: eight are extinguished, three were active until the year 2002 and the
      remaining five circulated in Venezuela during the years 2001-2007, illustrating
      the potential for FMDV diversification under appropriate selective pressure. The
      last emergencies reported in already-free areas of Colombia in 2004 and 2008 were
      closely related to isolates acting in Venzuela. Evidence of positive selection
      over codon 170, within the immunogenic site 4 of VP1 protein, was recorded. A
      codon deletion in amino acid position 142, within the G-H loop, was found in some
      isolates within subgenotypes 14, 15 and 16. Conversely amino acid deletion 197
      was restricted to all isolates within a particular genetic cluster. The present
      work is the first comprehensive phylogenetic analysis of FMDV type A in South
      America, filling a gap of knowledge with respect to both, historical and acting
      viruses. The results provided evidence that supports the ecosystem dynamics in
      the region, and also served as an input to establish genetic links of emergencies
      in already-declared free areas, highlighting the need for strengthening control
      activities.

PMID- 22397939
TI  - Proteome-determined type-specific proteins of Mycobacterium avium subspecies
      paratuberculosis.
AB  - Mycobacterium avium subspecies paratuberculosis (M. a. paratuberculosis) is a
      pathogen of ruminants, causing paratuberculosis (characterized by severe
      emaciation). The disease is endemic in many countries including the UK and places
      a severe economic burden on the global livestock industry. Two types of M. a.
      paratuberculosis can be classified by pulsed-field electrophoresis (I/III and
      II), which are phenotypically distinct and appear to have different host
      preferences. Proteomes of Type I and Type II M. a. paratuberculosis were analyzed
      by 2-D gel electrophoresis to determine if any significant differences existed
      between the subtypes. Seven different strains of Type I and 18 strains of Type II
      were analyzed and compared to detect type-specific differences. These 'type
      specific' differences existed regardless of growth phase and were also exhibited
      in cells isolated directly from pathogenic lesions. Twenty-three spots
      predominated on the Type I profile, from which 17 proteins were identified.
      Twenty-one spots predominated on the Type II profile, from which 16 proteins were
      identified. None of the proteins identified as differentially represented on the
      profiles of Type I or Type II corresponded to open reading frames of the defining
      genomic regions as previously described for the Type I (sheep) and Type II
      (cattle). Sequence polymorphisms existing in Type I and II strains were
      identified in some open reading frames or regulatory regions of genes that
      correspond to proteins expressed in a type-specific fashion. The consequence of
      these is discussed in relation to protein expression and their impact on the type
      phenotype is discussed.

PMID- 22397940
TI  - Phosphorylation status of matrix metalloproteinase 2 in myocardial ischaemia
      reperfusion injury.
AB  - OBJECTIVE: To investigate whether alterations in the phosphorylation status of
      matrix metalloproteinase 2 (MMP-2) in the heart may be protective in the setting
      of ischaemia-reperfusion (IR) injury. DESIGN: In-vitro heart function and
      biochemical research study. SETTING: University basic science laboratory.
      INTERVENTIONS: Male Sprague-Dawley rats, weighing 250-350 g. Isolated rat hearts
      were perfused at constant pressure either aerobically for 75 min or subjected to
      20 min of global, no-flow ischaemia followed by 30 min of reperfusion. MAIN
      OUTCOME MEASURES: Heart mechanical function, MMP-2 activity and troponin I
      levels. RESULTS: The serine/threonine phosphatase inhibitor okadaic acid (OA)
      improved the recovery of mechanical function compared with control IR hearts and
      prevented the loss of troponin I. OA significantly reduced protein phosphatase
      2A, but not protein phosphatase 1, activity in perfused hearts. IR stimulated the
      activation and release of MMP-2 into the coronary effluent in the first 2 min of
      reperfusion. This was accompanied by a decrease in the remaining activity and
      protein level of MMP-2 in heart tissue determined at the end of the reperfusion.
      OA did not alter the IR-stimulated release of MMP-2 into the coronary effluent,
      but reduced the decrease in MMP-2 in reperfused hearts. The immunoprecipitation
      of heart homogenates using anti-phosphoserine antibody showed that MMP-2 is
      phosphorylated. The dephosphorylation of MMP-2 by alkaline phosphatase treatment
      of homogenates prepared from IR hearts treated with OA significantly increased
      MMP-2 activity. CONCLUSIONS: These results suggest that the phosphorylation
      status of MMP-2 is important in its contribution to myocardial IR injury.

PMID- 22397941
TI  - B-type natriuretic peptide concentrations in contemporary Eisenmenger syndrome
      patients: predictive value and response to disease targeting therapy.
AB  - OBJECTIVE: To assess the relationship between elevated levels of B-type
      natriuretic peptide (BNP) and outcome in patients with Eisenmenger syndrome.
      DESIGN: Retrospective study. SETTING: Tertiary centre for adult congenital heart
      disease. PATIENTS: All patients with Eisenmenger syndrome (n=181, age 36.9+/-12.1
      years, 31% with Down syndrome) in whom BNP concentrations were measured as part
      of routine clinical care were included. MAIN OUTCOME MEASURES: The study end
      point was all cause mortality. RESULTS: During a median follow-up period of 3.3
      years, 20 patients (7 with Down syndrome) died. Higher BNP concentrations were
      predictive of all cause mortality on univariate analysis in patients with or
      without Down syndrome. On multivariable Cox proportional hazard analysis, BNP
      predicted survival independently of renal function, Down syndrome, or 6 min walk
      test distance (p=0.004). Temporal increases in BNP concentration were also found
      to predict mortality. Treatment with disease targeting therapies was associated
      with a significant reduction in BNP concentrations. CONCLUSIONS: BNP
      concentrations predict outcome in contemporary Eisenmenger patients. Increases in
      BNP concentrations over time are also of prognostic significance. In addition,
      disease targeting therapies may help to reduce BNP concentrations in this
      population, while treatment-naive patients have static or rising BNP
      concentrations.

PMID- 22397942
TI  - Is 7-day event triggered ECG recording equivalent to 7-day Holter ECG recording
      for atrial fibrillation screening?
AB  - OBJECTIVE: Prolonged ECG monitoring is standard for atrial fibrillation (AF)
      screening. This study investigated whether 7-day event triggered (tECG) ECG
      recording is equivalent to 7-day continuous Holter (cECG) ECG recording for AF
      screening. DESIGN: Both a cECG (Lifecard CF) and a tECG (R.Test Evolution 3) were
      simultaneously worn for 7 days by patients with known or suspected paroxysmal AF.
      RESULTS: In 100 corresponding recordings, median effective duration of monitoring
      was 165 h (range 10-170 h) for cECG and 137 h (0-169 h) for tECG (p<0.001).
      Median number and total duration of arrhythmias (AF, atrial flutter or atrial
      tachycardia) of >=30 s duration recorded by cECG were 10 (1-428) and 1030 min
      (<=1-10,020), respectively. An arrhythmia was recorded in 42 cECGs (42%) versus
      37 tECGs (37%, p=0.56). Triggered ECG failed to record an arrhythmia in cECG
      positive cases because of interrupted monitoring in four cases and because of
      recording failure in one case. Sensitivity, specificity, and positive and
      negative predictive values of tECG therefore were 88%, 100%, 100%, and 92%,
      respectively. Quantitative cECG analysis required a median of 20 min (3-205 min)
      and qualitative tECG analysis 4 min (1-20 min; p<0.001). Skin irritation was a
      frequent side effect (42%) resulting in premature removal of devices in 16% of
      patients. CONCLUSION: Sensitivity of tECG for AF screening as compared to cECG is
      lower, mainly because of shorter effective monitoring duration. Qualitative tECG
      analysis is less time consuming than quantitative cECG analysis. Skin irritation
      is a frequent side effect and reason for premature device removal.

PMID- 22397943
TI  - Clinical impact of intracoronary abciximab in patients undergoing primary
      percutaneous coronary intervention: an individual patient data pooled analysis of
      randomised studies.
AB  - OBJECTIVES: The aim of this study was to perform an individual patient-level
      pooled analysis of randomised trials, comparing intracoronary versus intravenous
      abciximab bolus use in patients with ST-segment elevation myocardial infarction
      (STEMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND:
      Abciximab represents a cornerstone in the treatment of STEMI patients undergoing
      primary PCI. Intracoronary abciximab bolus administration has been proposed as an
      alternative strategy to the standard intravenous route. However, whether
      intracoronary abciximab effectively improves clinical outcomes compared with
      standard route remains unknown. METHODS: Individual data of 1198 patients
      enrolled in five trials were entered into the pooled analysis. The primary
      endpoint of the study was the occurrence of all-cause death and reinfarction at
      30-day follow-up. Secondary endpoints were all-cause death, reinfarction and
      target-vessel revascularisation (TVR). RESULTS: No significant heterogeneity was
      found across trials. Compared with the intravenous route, intracoronary abciximab
      administration significantly reduced the risk of the composite of death and
      reinfarction (HR 0.52, 95% CI 0.29 to 0.94; p=0.03), death (HR 0.44, 95% CI 0.20
      to 0.95; p=0.04) and TVR (HR 0.53, 95% CI 0.29 to 0.99; p=0.045), without a
      significant impact on the risk of reinfarction (HR 0.54, 95% CI 0.24 to 1.21;
      p=0.13). However, after correction for baseline differences, only the composite
      of death/reinfarction and death remained significant. CONCLUSIONS: In STEMI
      patients undergoing primary PCI, intracoronary abciximab administration, when
      compared with the intravenous standard route, can improve short-term clinical
      outcomes mainly by reducing the risk of death.

PMID- 22397944
TI  - Effectiveness of the LUCAS device for mechanical chest compression after cardiac
      arrest: systematic review of experimental, observational and animal studies.
AB  - CONTEXT: The LUCAS mechanical chest compression device may be better than manual
      chest compression during resuscitation attempts after cardiac arrest. OBJECTIVE:
      To summarise the evidence about the effectiveness of LUCAS. DATA SOURCES:
      Searches of 4 electronic databases, reference lists of included studies, review
      articles, clinical guidelines, and the manufacturer's web site. No language
      restrictions were applied. Date of last search: September 2011. STUDY SELECTION:
      All studies, of any design, comparing mechanical chest compression using LUCAS
      with manual chest compression, with human or animal subjects. Studies published
      only as abstracts were included. Manikin studies, and case reports or case
      series, were excluded. DATA EXTRACTION: Data were extracted on study methodology
      and outcomes, including return of spontaneous circulation, survival, injuries
      caused by resuscitation, and physiological parameters. RESULTS: 22 papers
      reporting 16 separate studies were included. There was one randomised trial, nine
      cohort studies, 2 before/after studies and 4 animal studies. No meta-analyses
      were performed because of high risk of bias and heterogeneity in the study
      designs. Animal studies suggested an advantage to LUCAS in terms of physiological
      parameters, but human studies did not suggest an advantage in ROSC or survival.
      Existing evidence is low quality because most studies were small and many were
      poorly reported. CONCLUSIONS: There is insufficient evidence to make any
      recommendations for clinical practice. Large scale, high quality randomised
      trials of LUCAS are needed. Studies that have so far been published only as
      abstracts should be reported fully.

PMID- 22397945
TI  - Risk prediction models: I. Development, internal validation, and assessing the
      incremental value of a new (bio)marker.
AB  - Prediction models are increasingly used to complement clinical reasoning and
      decision making in modern medicine in general, and in the cardiovascular domain
      in particular. Developed models first and foremost need to provide accurate and
      (internally and externally) validated estimates of probabilities of specific
      health conditions or outcomes in targeted patients. The adoption of such models
      must guide physician's decision making and an individual's behaviour, and
      consequently improve individual outcomes and the cost-effectiveness of care. In a
      series of two articles we review the consecutive steps generally advocated for
      risk prediction model research. This first article focuses on the different
      aspects of model development studies, from design to reporting, how to estimate a
      model's predictive performance and the potential optimism in these estimates
      using internal validation techniques, and how to quantify the added or
      incremental value of new predictors or biomarkers (of whatever type) to existing
      predictors. Each step is illustrated with empirical examples from the
      cardiovascular field.

PMID- 22397946
TI  - Risk prediction models: II. External validation, model updating, and impact
      assessment.
AB  - Clinical prediction models are increasingly used to complement clinical reasoning
      and decision-making in modern medicine, in general, and in the cardiovascular
      domain, in particular. To these ends, developed models first and foremost need to
      provide accurate and (internally and externally) validated estimates of
      probabilities of specific health conditions or outcomes in the targeted
      individuals. Subsequently, the adoption of such models by professionals must
      guide their decision-making, and improve patient outcomes and the cost
      effectiveness of care. In the first paper of this series of two companion papers,
      issues relating to prediction model development, their internal validation, and
      estimating the added value of a new (bio)marker to existing predictors were
      discussed. In this second paper, an overview is provided of the consecutive steps
      for the assessment of the model's predictive performance in new individuals
      (external validation studies), how to adjust or update existing models to local
      circumstances or with new predictors, and how to investigate the impact of the
      uptake of prediction models on clinical decision-making and patient outcomes
      (impact studies). Each step is illustrated with empirical examples from the
      cardiovascular field.

PMID- 22397947
TI  - Non-canonical Notch signaling: emerging role and mechanism.
AB  - Notch is an ancient transmembrane receptor with crucial roles in cell-fate
      choices. Although the 'canonical' Notch pathway and its core members are well
      established - involving ligand-induced cleavage of Notch for transcriptional
      regulation - it has been unclear whether Notch can also function independently of
      ligand and transcription ('non-canonically') through a common mechanism. Recent
      studies suggest that Notch can non-canonically exert its biological functions by
      post-translationally targeting Wnt/beta-catenin signaling, an important cellular
      and developmental regulator. The non-canonical Notch pathway appears to be highly
      conserved from flies to mammals. Here, we discuss the emerging conserved
      mechanism and role of ligand/transcription-independent Notch signaling in cell
      and developmental biology.

PMID- 22397948
TI  - Dynamics of receptor trafficking in tumorigenicity.
AB  - The transport and sorting of cell surface receptors into membrane-bound
      intracellular compartments is crucial for cellular homeostasis. Defects in
      receptor trafficking are associated with several diseases, including cancer.
      Recent advances in our understanding of mechanisms that control receptor
      trafficking have highlighted the involvement of membrane trafficking in cell
      signaling, as well as in biological processes, including cell migration and
      invasion. In this review, we summarize current knowledge of how cargos, focusing
      on receptor tyrosine kinases (RTKs) and integrins, are dynamically transported
      through the endosomal pathway for recycling, and how this promotes spatially
      restricted signaling microdomains associated with distinct biological responses.
      We discuss mechanisms through which dysregulation of membrane trafficking
      contributes to tumorigenesis and potential therapeutic approaches.

PMID- 22397949
TI  - A boundedness result for the direct heuristic dynamic programming.
AB  - Approximate/adaptive dynamic programming (ADP) has been studied extensively in
      recent years for its potential scalability to solve large state and control space
      problems, including those involving continuous states and continuous controls.
      The applicability of ADP algorithms, especially the adaptive critic designs has
      been demonstrated in several case studies. Direct heuristic dynamic programming
      (direct HDP) is one of the ADP algorithms inspired by the adaptive critic
      designs. It has been shown applicable to industrial scale, realistic and complex
      control problems. In this paper, we provide a uniformly ultimately boundedness
      (UUB) result for the direct HDP learning controller under mild and intuitive
      conditions. By using a Lyapunov approach we show that the estimation errors of
      the learning parameters or the weights in the action and critic networks remain
      UUB. This result provides a useful controller convergence guarantee for the first
      time for the direct HDP design.

PMID- 22397950
TI  - Connectivity and thought: the influence of semantic network structure in a
      neurodynamical model of thinking.
AB  - Understanding cognition has been a central focus for psychologists,
      neuroscientists and philosophers for thousands of years, but many of its most
      fundamental processes remain very poorly understood. Chief among these is the
      process of thought itself: the spontaneous emergence of specific ideas within the
      stream of consciousness. It is widely accepted that ideas, both familiar and
      novel, arise from the combination of existing concepts. From this perspective,
      thought is an emergent attribute of memory, arising from the intrinsic dynamics
      of the neural substrate in which information is embedded. An important issue in
      any understanding of this process is the relationship between the emergence of
      conceptual combinations and the dynamics of the underlying neural networks.
      Virtually all theories of ideation hypothesize that ideas arise during the
      thought process through association, each one triggering the next through some
      type of linkage, e.g., structural analogy, semantic similarity, polysemy, etc. In
      particular, it has been suggested that the creativity of ideation in individuals
      reflects the qualitative structure of conceptual associations in their minds.
      Interestingly, psycholinguistic studies have shown that semantic networks across
      many languages have a particular type of structure with small-world, scale free
      connectivity. So far, however, these related insights have not been brought
      together, in part because there has been no explicitly neural model for the
      dynamics of spontaneous thought. Recently, we have developed such a model. Though
      simplistic and abstract, this model attempts to capture the most basic aspects of
      the process hypothesized by theoretical models within a neurodynamical framework.
      It represents semantic memory as a recurrent semantic neural network with
      itinerant dynamics. Conceptual combinations arise through this dynamics as co
      active groups of neural units, and either dissolve quickly or persist for a time
      as emergent metastable attractors and are recognized consciously as ideas. The
      work presented in this paper describes this model in detail, and uses it to
      systematically study the relationship between the structure of conceptual
      associations in the neural substrate and the ideas arising from this system's
      dynamics. In particular, we consider how the small-world and scale-free
      characteristics influence the effectiveness of the thought process under several
      metrics, and show that networks with both attributes indeed provide significant
      advantages in generating unique conceptual combinations.

PMID- 22397951
TI  - Massively parallel neural encoding and decoding of visual stimuli.
AB  - The massively parallel nature of video Time Encoding Machines (TEMs) calls for
      scalable, massively parallel decoders that are implemented with neural
      components. The current generation of decoding algorithms is based on computing
      the pseudo-inverse of a matrix and does not satisfy these requirements. Here we
      consider video TEMs with an architecture built using Gabor receptive fields and a
      population of Integrate-and-Fire neurons. We show how to build a scalable
      architecture for video Time Decoding Machines using recurrent neural networks.
      Furthermore, we extend our architecture to handle the reconstruction of visual
      stimuli encoded with massively parallel video TEMs having neurons with random
      thresholds. Finally, we discuss in detail our algorithms and demonstrate their
      scalability and performance on a large scale GPU cluster.

PMID- 22397952
TI  - Current status of cytoreductive surgery with hyperthermic intraperitoneal
      chemotherapy in patients with peritoneal carcinomatosis from colorectal cancer.
AB  - Peritoneal carcinomatosis (PC) arising from colorectal cancer (CRC) is generally
      considered a terminal condition with no treatment options. However novel
      treatment strategies have emerged combining cytoreductive surgery (CRS),
      including peritonectomy procedures, with intraperitoneal chemotherapy. The
      intraoperative application of cytotoxic drugs combined with hyperthermia
      (hyperthermic intraperitoneal chemotherapy [HIPEC]) has been considered to
      deliver cytotoxicity most effectively to peritoneal tumor implants. In selected
      groups of patients with no remaining macroscopic tumor manifestations on
      peritoneal surfaces after CRS and HIPEC, median survival times may reach 5 years,
      with a 5 year overall survival rate of 50%. HIPEC has been performed with
      different cytotoxic drugs, in combination with early postoperative
      intraperitoneal chemotherapy (EPIC), and embedded into various systemic
      perioperative and/or postoperative chemotherapeutic regimens. Prognosis largely
      depends on the intraabdominal tumor burden, which can be assessed by the
      peritoneal cancer index (PCI), and the completeness of cytoreduction. In this
      review we discuss the most relevant prognostic parameters, the outcome of
      patients with PC from CRC treated with CRS and HIPEC, and the impact of different
      chemotherapeutic variations used during HIPEC. From this analysis it can be
      concluded that CRS and HIPEC offers a chance for long-term survival in selected
      patients with PC of colorectal origin.

PMID- 22397953
TI  - IL-6 receptor inhibition positively modulates bone balance in rheumatoid
      arthritis patients with an inadequate response to anti-tumor necrosis factor
      therapy: biochemical marker analysis of bone metabolism in the tocilizumab
      RADIATE study (NCT00106522).
AB  - OBJECTIVE: To evaluate changes in biochemical markers of bone metabolism in
      response to tocilizumab in patients with anti-tumor necrosis factor-refractory
      rheumatoid arthritis (RA). METHODS: RADIATE was a randomized, double-blind,
      placebo-controlled, parallel-group phase 3 trial. C-reactive protein, osteocalcin
      (OC), C-terminal telopeptides of type-I collagen (C-terminal telopeptides of type
      1 collagen (CTX-I) and type-I collagen degradation product), and matrix
      metalloproteinase-3 (MMP-3) serum levels were analyzed from 299 RA patients.
      Patients were randomly assigned to either tocilizumab (4 or 8 mg/kg) or placebo
      intravenously every 4 weeks, along with concomitant stable methotrexate (10 to 25
      mg weekly) in all treatment arms. The change in biochemical markers CTX-I and OC
      in combination was evaluated as a measure of net bone balance, a reflection of
      the change in equilibrium between resorption and formation. RESULTS: Both
      tocilizumab doses decreased C-reactive protein levels and significantly inhibited
      cathepsin K-mediated bone resorption in RADIATE subjects, as measured by a
      decrease in CTX-I. There was a significant overall improvement in net bone
      balance at week 16 as measured by a decrease in the CTX-I:OC ratio (-25%, P <
      0.01). Furthermore, a significant reduction in MMP-3 (43%, P < 0.001) and type-I
      collagen degradation product levels (18%, P < 0.001) were observed following
      treatment, both consistent with decreased MMP-mediated type-I collagen catabolism
      in joint tissue. CONCLUSIONS: In anti-tumor necrosis factor-refractory patients,
      tocilizumab significantly reduced the levels of biochemical markers of cathepsin
      K-mediated bone resorption and MMP-mediated tissue degradation and remodeling.
      These observations suggest that tocilizumab has a positive effect on bone
      balance, which could in part explain the retardation of progressive structural
      damage observed with tocilizumab. Clinical trial registry number: NCT00106522.

PMID- 22397954
TI  - Outcomes of trabeculectomy after descemet stripping automated endothelial
      keratoplasty: a comparison with penetrating keratoplasty.
AB  - PURPOSE: To compare the outcomes of trabeculectomy surgery after Descemet
      stripping automated endothelial keratoplasty (DSAEK) to penetrating keratoplasty
      (PK). DESIGN: Retrospective case-control study. METHODS: Patients within an
      institutional setting who underwent trabeculectomy with mitomycin C (MMC) for
      uncontrolled elevated intraocular pressure (IOP) after corneal graft surgery were
      included. Patients with pre-existing glaucoma were excluded. Twenty patients with
      trabeculectomy after DSAEK and 41 patients with trabeculectomy after PK were
      analyzed. The main outcome measure was IOP control at 12 months. Secondary
      outcome measures were postoperative interventions including reinstatement of IOP
      lowering medications, bleb needling with 5-fluorouracil (5FU) or further glaucoma
      surgery, and the incidence of complications related to trabeculectomy and/or
      corneal graft surgery. RESULTS: There was no difference in pre-trabeculectomy IOP
      between DSAEK vs PK group (35.5 +/- 10.1 vs 32.9 +/- 8.9, P = .31). At 12 months
      after trabeculectomy, mean IOP in the DSAEK group was lower compared to the PK
      controls (10.6 +/- 3.2 vs 14.6 +/- 8.5, P = .04). The proportion of patients who
      achieved an IOP less than 12 mm Hg was significantly higher in the DSAEK group
      (80.0% vs 48.6%, P = .03). The proportions of eyes that required intervention
      after trabeculectomy were comparable between the 2 groups (DSAEK vs PK, all
      interventions: 20.0% vs 39.5%, P = .15; IOP-lowering medications required: 15.0%
      vs 39.5%, P = .08; needling with 5FU: 20.0% vs 23.7%, P > .99; further glaucoma
      surgery: 0% vs 13.2%, P = .15). Corneal graft failure arising after
      trabeculectomy was seen in 10.0% of DSAEK cases and in 10.5% of PK controls (P =
      1.0). CONCLUSION: Compared to trabeculectomy after PK, trabeculectomy after DSAEK
      achieved lower mean IOP at 12 months, and a larger proportion of DSAEK patients
      achieved an IOP of less than 12 mm Hg. There was no difference in the need for
      intervention after trabeculectomy, or incidence of other complications.
      Trabeculectomy is an effective surgical procedure for the management of postgraft
      ocular hypertension in DSAEK patients, and DSAEK may have an advantage in terms
      of success of trabeculectomy surgery over PK.

PMID- 22397955
TI  - Descemet membrane endothelial keratoplasty versus descemet stripping automated
      endothelial keratoplasty.
AB  - PURPOSE: To evaluate visual outcome and endothelial cell survival after Descemet
      membrane endothelial keratoplasty (DMEK) in comparison with Descemet stripping
      automated endothelial keratoplasty (DSAEK). DESIGN: Single-center, retrospective,
      consecutive case series. METHODS: Thirty-eight eyes of 38 consecutive patients
      undergoing DMEK, who completed a 6-month follow-up, were compared with 35 eyes of
      35 consecutive patients undergoing DSAEK for Fuchs endothelial dystrophy or
      pseudophakic bullous keratopathy. Main outcome measures included best-corrected
      visual acuity (in logarithm of the minimal angle of resolution [logMAR] units)
      and endothelial cell density within a 6-month follow-up. RESULTS: Best-corrected
      visual acuity increased from 0.70 +/- 0.48 logMAR and 0.75 +/- 0.32 logMAR before
      surgery to 0.21 +/- 0.14 logMAR and 0.48 +/- 0.19 logMAR 3 months after DMEK and
      DSAEK (P < .001), respectively, and to 0.17 +/- 0.12 logMAR and 0.36 +/- 0.15
      logMAR 6 months after DMEK and DSAEK (P < .001), respectively. Endothelial cell
      density decreased from 2575 +/- 260 cells/mm(2) and 2502 +/- 220 cells/mm(2)
      before surgery to 1498 +/- 244 cells/mm(2) and 1778 +/- 420 cells/mm(2) 3 months
      after DMEK and DSAEK (P < .001), respectively, and to 1520 +/- 299 cells/mm(2)
      and 1532 +/- 495 cells/mm(2) 6 months after DMEK and DSAEK (P = .483),
      respectively. Central corneal thickness decreased from 652 +/- 92 MUm before
      surgery to 517 +/- 45 MUm 6 months after DMEK, and from 698 +/- 137 MUm before
      surgery to 618 +/- 66 MUm 6 months after DSAEK. CONCLUSIONS: DMEK provided faster
      and more complete visual rehabilitation when compared with DSAEK. However, there
      were no significant differences concerning endothelial cell survival within a 6
      month follow-up.

PMID- 22397956
TI  - Macular choroidal thickness and volume in eyes with angioid streaks measured by
      swept source optical coherence tomography.
AB  - PURPOSE: To study the mean choroidal thickness and volume of the macula in eyes
      with angioid streaks using swept source optical coherence tomography (OCT) in the
      1050-nm wavelength range. DESIGN: Prospective case series. METHODS: The macular
      area of 39 eyes of 23 patients with angioid streaks and of 20 normal eyes of 20
      matched controls (Group 1) was studied with a swept source OCT prototype system.
      Eyes with angioid streaks were classified into 1 of 4 groups: those without
      choroidal neovascularization (CNV) (Group 2); those with CNV that had no history
      of treatment (Group 3); those with CNV that had previously received only anti
      vascular endothelial growth factor treatments (Group 4); and those with CNV that
      had previously received photodynamic therapy (Group 5). Using a raster scan
      protocol with 512 * 128 A-scans, we produced a macular choroidal thickness map (6
      * 6 mm(2)). RESULTS: There were no significant differences in age, axial length,
      or refractive error among the 5 groups. Mean choroidal thickness of the macula in
      Group 2 (218.9 +/- 46.8 MUm) was as great as that in Group 1 (218.8 +/- 69.2
      MUm). However, the macular choroidal thickness in Group 3 (119.7 +/- 49.2 MUm),
      Group 4 (140.1 +/- 64.9 MUm), and Group 5 (144.0 +/- 52.6 MUm) was significantly
      less than that of Group 1 (P < .05). There were no statistical differences
      between Groups 3 through 5. In each group, the choroid of the nasal quadrant was
      significantly thinner compared to that in other quadrants (P < .05). CONCLUSIONS:
      The choroid in eyes with angioid streaks without CNV was as thick as that in
      normal controls, but was significantly thinner in eyes with angioid streaks that
      had developed CNV.

PMID- 22397957
TI  - Dietetic students' identity and professional socialization in preparation for
      practice.
AB  - PURPOSE: Students' identity development and professional socialization during
      dietetic education were explored. METHODS: Thirteen undergraduate dietetic
      students from two universities completed three in-depth interviews based on
      Seidman's phenomenological approach. The students were at various stages of their
      education. Data were analyzed with a feminist form of inductive thematic
      analysis. RESULTS: Dietetic students come to the educational process with a broad
      interest in health, helping, or foods and nutrition. The academic and practical
      components of dietetic education create opportunities for students to refine
      personal interests in order to (re-)envision their place within the profession.
      The complexity of professional socialization and identity development was
      illuminated as some students' focus was redirected to becoming an intern rather
      than becoming a dietitian. Students transformed their identity to meet the
      requirements they thought were expected or necessary to obtain an internship.
      Internship competition and the program environment can influence this
      transformation. CONCLUSIONS: Professional identity development begins before
      dietetic education and develops within the context of that education,
      representing the intersection of both people and events. A recognition and
      understanding of these complexities can result in strategic recruitment, informed
      curriculum changes, and professional development opportunities for dietetic
      educators, which will enhance their ability to support students in the
      professional socialization process.

PMID- 22397958
TI  - Dietary intake of Nova Scotia youth in grades 7 and 11.
AB  - PURPOSE: We examined dietary intakes among Nova Scotia youth, and analyzed
      whether these intakes met existing dietary guidelines. METHODS: Data from 1469
      students in grades 7 and 11 from randomly selected schools were collected via a
      web-based dietary assessment tool, including a 24-hour recall. Nutrient analysis
      products were subjected to descriptive and inferential statistical analyses.
      RESULTS: Reported dietary intakes across sexes and grades showed the vast
      majority of youth did not meet minimum recommendations for fibre (96% to 98%) or
      vegetable and fruit servings (83.3% to 90.7%). Girls in grade 11 reported greater
      intakes of folate and lower intakes of saturated fat, and were less likely to
      report iron intakes at or above the Estimated Average Requirement than were grade
      7 girls. Across ages, more than 75% of girls reported low calcium and folate
      intakes. Boys in both grades reported consuming more energy than did girls, and
      older boys reported consuming more than did younger boys. Foods outside the four
      main food groups contributed about 25% of total reported energy intake. Students
      in grade 7 consumed pop, salty snacks, and french fries more frequently than did
      students in grade 11. CONCLUSIONS: Adolescents' self-reported dietary intakes may
      not meet current dietary recommendations. Continued efforts are needed to develop
      innovative strategies to ensure healthy eating patterns.

PMID- 22397959
TI  - [Food environment in childcare settings in Quebec: results from a descriptive
      study].
AB  - PURPOSE: The goal of this study was to describe different components of the food
      environment in childcare settings. METHODS: Visits were made to 33 early
      childcare centres (CPEs) in the Estrie region of Quebec, Canada. Data were
      collected between March and July 2008 using a questionnaire based on the Cohen
      model. The goal of the questionnaire was to collect information about meal
      organization, menu composition and food preparation methods. RESULTS: Although
      few CPEs had adopted a food policy, descriptive analyses showed that the food
      environment in these settings was generally adequate. In 97% of the CPEs, menu
      planning was performed by the food technician. The meals offered as well as the
      food preparation methods employed were consistent with the general guidelines of
      Canada's Food Guide (CFG). However, a lack of professional training was observed.
      Furthermore, only 25% of the CPEs offered a snack made up of two food groups.
      CONCLUSIONS: Certain improvements must be made to the food environment in Quebec
      childcare settings, which underscoresthe need to create and implement a food
      policy for childcare centres.

PMID- 22397960
TI  - Sodium reduction in Canadian food products with the health check program.
AB  - PURPOSE: The current Health Check criteria were examined, to evaluate their
      influence on prompting licensees to reduce sodium in their participating products
      from 2004 to 2008. In addition, the impact of the new Health Check criteria,
      implemented in November 2010, was explored. METHODS: Over three months, 14 Health
      Check program licensees representing 371 products completed a researcher
      administered questionnaire, either in person or via conference call. The data
      were recorded, reviewed, and calculated. Participants verified the data after the
      interview. RESULTS: The current criteria prompted product reformulations and new
      formulations among Health Check participants. One hundred and fifty products had
      sodium reduced to meet the current Health Check criteria, for a total reduction
      of over 322,000 kg of sodium. New formulations comprised 116 products; the
      remaining 105 products met the current criteria. Two hundred of the 371 Health
      Check products that had been reformulated, that met the criteria, or that were
      new formulations already meet the new 2010 Health Check criteria. CONCLUSIONS:
      The Health Check program prompted participants to reformulate existing products
      or formulate new products to meet the criteria for sodium. All participants
      agreed that the new 2010 Health Check criteria will affect them.

PMID- 22397961
TI  - Phase II Practice-based Evidence in Nutrition (PEN) evaluation: interviews with
      key informants.
AB  - PURPOSE: Dietitians of Canada has collaborated with experts in knowledge
      translation and transfer, technology, and dietetic practice to develop and
      implement an innovative online decision-support system called Practice-based
      Evidence in Nutrition (PEN). A study was conducted to evaluate the perceived
      facilitators and barriers that enable dietitians to use or prevent them from
      using PEN. METHODS: As part of the overall evaluation framework of PEN, a
      qualitative descriptive research design was used to address the research purpose.
      Individual, semi-structured telephone interviews with 17 key informants were
      completed, and the interview transcripts underwent qualitative content analysis.
      RESULTS: Respondents identified several facilitators of and barriers to PEN use.
      Facilitators included specificity to dietetics, rigorous/expert review, easy
      accessibility, current content, credible/secure material, well-organized/easy-to
      use material, material that is valuable to practice, and good value for money.
      Barriers included perceived high cost, fee structuring/cost to students, certain
      organizational aspects, and a perceived lack of training for pathway
      contributors. CONCLUSIONS: This formative evaluation has indicated areas in which
      PEN could be improved and strategies to make PEN the standard for dietetic
      education and practice. Ensuring that PEN is meeting users' knowledge needs is of
      the utmost importance if dietitians are to remain on the cutting edge of
      scientific inquiry.

PMID- 22397962
TI  - Employers' perspectives of students in a master of public health (nutrition)
      program.
AB  - Efforts to support workforce development led to the launch of a new master of
      public health program aimed at improving access to graduate studies for
      practising nutrition professionals. The first cohort of students identified
      employer support as a key determinant of their success. In order to identify ways
      of addressing both student and employer needs, we explored the perspectives of
      students' employers. Seventeen in-depth, semi-structured, open-ended interviews
      were conducted with employers. Interviews were audiotaped and transcribed.
      Transcripts were organized using NVivo software and coded thematically. All
      employers indicated support for employee education and development in principle,
      but most faced practical challenges related to limited staffing during education
      leaves. Organizational policies varied considerably across employer groups.
      Collective agreements that guided education policy were seen to ensure consistent
      support for employees, but also to limit creative approaches to education support
      in some situations. Employers highly valued graduate student projects that were
      directly related to the workplace; these projects presented opportunities for
      collaboration among the university, students, and employers. Universities need to
      work with employers and other stakeholders to identify ways of overcoming
      barriers to public health nutrition graduate education and workforce development.

PMID- 22397963
TI  - Regulatory approval of plant sterols in Canada: implications for health care and
      clinical practice.
AB  - Health Canada's recent approval of plant sterols as food ingredients to decrease
      low-density lipoprotein cholesterol (LDL-C) is believed to be a significant step
      toward improving Canadians' cardiovascular health and reducing the economic
      burden of heart disease. When dyslipidemic patients consume plant sterols at a
      recommended daily dose of 2 g, they can reduce LDL-C by 10% to 15%, with no
      deleterious effects on high-density lipoprotein cholesterol. A 10% LDL-C
      reduction in response to plant sterol consumption is projected to reduce heart
      disease risk by 25%. Because they are available without a prescription, plant
      sterols are an option for dietitians who wish to provide cholesterol-lowering
      guidance beyond traditional dietary advice (i.e., lowering saturated fat intake
      and restricting dietary cholesterol). In addition, plant sterols can be used in
      combination with a statin or when statin use is contraindicated, and they have
      recently emerged as a potentially valuable triglyceride-lowering option. However,
      the projected improvement in public health and health care savings will be
      realized only if impediments to daily use are removed. One such impediment is the
      higher cost of fortified food products, such as yogurt and margarine. If the cost
      of plant sterol food products is to decline, cost-effective sources must be
      investigated and a larger range of foods containing plant sterols must be made
      available.

PMID- 22397964
TI  - Availability of nutrition screening parameters in New Brunswick hospitals and
      nursing homes.
AB  - We explored the availability of parameters for a nutrition screening system among
      elderly people in New Brunswick (NB) health care facilities. Patients aged 65 or
      older were asked to participate in the study; each participant had been admitted
      to one of four hospitals or lived in one of six nursing homes. Availability of
      nutrition screening parameters (weight, height, weight change, serum albumin
      level, appetite, and food intake record) was assessed by auditing the
      participants' medical charts. When data were not available, the feasibility of
      obtaining them was determined. Additional data related to nutrition screening
      were also obtained. In total, 421 participants were recruited for the study: 140
      (33.2%) who lived in nursing homes and 281 (66.8%) who were in hospitals.
      Parameters needed to conduct nutrition screening, such as weight upon admission,
      were available for 83.6% of participants; usual weight was available for 43.0%,
      height for 86.0%, and serum albumin level for 47.5%. Our findings show that basic
      parameters for nutrition screening are available, and that implementation of a
      nutrition screening system is feasible for patients in NB health care facilities.

PMID- 22397965
TI  - Development of a food frequency questionnaire for toddlers of Low-German-Speaking
      Mennonites from Mexico.
AB  - PURPOSE: Little is known about dietary intakes in toddlers of Low-German-Speaking
      Mennonites from Mexico, although some of these toddlers might be at risk for
      nutritional deficiencies. A 97-item, culturally sensitive, interviewer
      administered food frequency questionnaire (FFQ) was developed and validated for
      health professionals to assess dietary intake in these children aged 12 to 36
      months. METHODS: Cultural foods on the FFQ were determined via focus groups; a
      pilot study tested content and formatting. The FFQ was administered to
      parents/caregivers of 22 toddlers in a southern Ontario community of Low-German
      Speaking Mennonites from Mexico. Validity was determined by comparing nutrient
      intakes from the FFQ and from the 24-hour recalls, using Bland-Altman plots,
      Pearson correlations, and Student's t-tests. Test-retest reliability was compared
      between two FFQ administrations (n=14) one month apart, via intraclass
      correlations (ICCs). RESULTS: Bland-Altman plots showed good agreement between
      the FFQ and the 24-hour recall; Pearson correlations between methods were
      significant for protein, folate, calcium, and caffeine. Student's t-tests were
      not significantly different between methods for 11 of 12 nutrients. Test-retest
      reliability was good on the basis of acceptable ICC for eight of 12 nutrients.
      CONCLUSIONS: The prevalence of nutrient inadequacies was low, except for folate.
      These results are promising for implementation of a simple, quick, culturally
      sensitive FFQ with the potential to provide reliable estimates of mean intakes in
      toddlers of Low-German-Speaking Mennonites from Mexico.

PMID- 22397966
TI  - Body fat, sweetness sensitivity, and preference: determining the relationship.
AB  - PURPOSE: The study was conducted to evaluate whether body fat is a better measure
      than body mass index (BMI) for determining the relationship between body size and
      sweetness perception and preference. METHODS: Seventy-two women were recruited
      and separated into two groups. First, BMI was determined and used to classify
      each woman as either normal weight (18.5 to 24.9 kg/m2) or overweight (>25.0
      kg/m2). Body fat was determined from skinfold sites and used to categorize women
      into normal (<26.0%) or overweight body fat (=26%) groups. Detection thresholds
      were determined using sucrose solutions. Four custard samples that varied in
      sweetness were evaluated to determine the women's liking for sweetness, and the
      perceived sweetness of the sample. RESULTS: Women in the overweight BMI and body
      fat groups had higher sucrose threshold values than did women in the normal
      groups. When presented with custards of varying sucrose levels, the overweight
      BMI and body fat groups had a significantly increased liking for sweetness as
      sucrose concentration increased. CONCLUSIONS: Body fat measures were as effective
      as BMI measures in determining sweetness preference. Future research should be
      conducted to determine whether body fat and measures, such as waist
      circumference, can be predictive tools for sweetness preference.

PMID- 22397968
TI  - Cytokine production and proliferation upon in vitro oligodeoxyribonucleotide
      stimulation of equine peripheral blood mononuclear cells.
AB  - Synthetic oligodeoxyribonucleotides (ODN) may prove useful immune modulators in
      equine medicine. It is however important to assess the effects of each specific
      ODN in the species it is intended to be used in. The present study therefore
      aimed to evaluate some ODN for induction of cytokine production; i.e. type I
      interferons (IFN), IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) and
      transforming growth factor-beta (TGF-beta), and proliferation of equine
      peripheral blood mononuclear cells (PBMC). A panel of four ODN containing
      unmethylated cytosine-guanosine sequences (CpG) was used: ODN 1 and ODN 8
      representing A-class; ODN 2006 representing B-class and ODN 2395 representing C
      class-ODN. In addition, two ODN where CpG-motifs were reversed to GpC were
      included; ODN 2137 otherwise identical to ODN 2006 and ODN 5328 otherwise
      identical to ODN 2395. Cytokine concentrations were measured in cell culture
      supernatants after 24h of induction and proliferation was determined after 72 h
      of induction. Each ODN was tested with PBMC from at least 5 individual horses
      with and without the addition of lipofectin to cell cultures. Type I IFN, IFN
      gamma and TNF-alpha production was readily induced by ODN 1, ODN 2006 and ODN
      2395 both in the presence and absence of lipofectin and all three types of ODN
      induced similar levels of cytokines. Proliferation of PBMC was clearly induced by
      ODN 2006 and ODN 2395 while ODN 1 only induced low-level proliferation. The
      levels of proliferation induced were not influenced by the presence of
      lipofectin. TGF-beta production was not induced by any of the tested ODN. ODN 8,
      ODN 2137 and ODN 5328 were largely inactive in all assays. Thus, responses seemed
      dependent on or increased by CpG-motifs but presence of CpG-motifs did not
      necessarily confer activity since ODN 8 was inactive despite its CpG-motifs.
      Taken together, with equine PBMC distinctions in induction of different leukocyte
      functions between A-, B-, and C-class ODN were less obvious than what has been
      observed for human cells. These observations further stress the presence of
      species differences in ODN-induced responses.

PMID- 22397969
TI  - Endodermal cyst of the third cranial nerve.

PMID- 22397970
TI  - Historical considerations of the predominance of lumboperitoneal shunt for
      treatment of adult communicating hydrocephalus in Kumamoto, Japan.

PMID- 22397971
TI  - Cerebellar anaplastic pilocytic astrocytoma in a patient of neurofibromatosis
      type-1: case report and review of the literature.

PMID- 22397972
TI  - Salt-and-pepper eye pain and brainstem stroke.
AB  - BACKGROUND AND PURPOSE: The salt-and-pepper pain is a characteristic sensory
      disturbance confined to the eyes and regional facial structures. Although a poor
      prognosis has been mentioned in previously reported patients, the precise
      pathomechanism and clinical significance are still unknown. PATIENTS AND METHODS:
      We report four patients with ocular salt-and-pepper pain, and review the clinical
      course, neuroimaging and prognosis in another eight patients reported in the
      literature. RESULTS: In our series, they were three men and one woman, and their
      underlying cause was pontine hemorrhage; hypertensive hemorrhage in three and
      cavernous hemangioma in one patient, respectively. In these 12 salt-and-pepper
      patients, the identifiable etiology was exclusively brainstem stroke. Life
      threatening or disable neurological deterioration ensued within 24 h after pain
      onset in all patients. Their ocular pain subsided rapidly after neurological
      deterioration occurred. A dual excitation of nociceptive quinothalamic pain fiber
      and disinhibition of trigeminosensory system from pontine reticular formation and
      cerulotrigeminospinal circuit may be responsible for this pain. CONCLUSION: In
      clinical practice, ocular salt-and-pepper pain in quiet eyes should be alerted
      for intracranial pathology and neurological deterioration until underlying cause
      is identified.

PMID- 22397973
TI  - A highly efficient Agrobacterium mediated transformation system for chickpea wilt
      pathogen Fusarium oxysporum f. sp. ciceri using DsRed-Express to follow root
      colonisation.
AB  - The soil-borne fungus Fusarium oxysporum f. sp. ciceri (Foc) causes vascular wilt
      of chickpea (Cicer arietinum L.), resulting in substantial yield losses
      worldwide. Agrobacterium tumefaciens mediated transformation (ATMT) has served as
      a resourceful tool for plant-pathogen interaction studies and offers a number of
      advantages over conventional transformation systems. Here, we developed a highly
      efficient A. tumefaciens mediated transformation system for Foc. In addition, a
      binary vector for constitutive expression of red fluorescent protein (DsRed
      Express) was used to study developmental stages and host-pathogen interactions.
      Southern hybridisation was performed to confirm the transformation event and the
      presence of T-DNA in selected hygromycin resistant transformants. Most of the
      transformants showed single copy integrations at random positions. Microscopic
      studies revealed significant levels of fluorescent protein, both in conidia and
      mycelia. Confocal microscopy of chickpea roots infected with the transformed Foc
      showed rapid colonisation. These studies will allow us to develop strategies to
      determine the mechanisms of Foc-chickpea interaction in greater detail and to
      apply functional genomics for the characterisation of involved genes at the
      molecular level either by insertional mutagenesis or gene knock-out.

PMID- 22397974
TI  - Tmac1, a transcription factor which regulated high affinity copper transport in
      Trichoderma reesei.
AB  - The Mac1 protein was a transcriptional activator that sensed very low
      concentration of copper and regulated the copper transport in Saccharomyces
      cerevisiae. Here, we cloned a gene from Trichoderma reesei named Tmac1, whose
      deduced amino acid sequence showed 29% identical to Mac1p. Furthermore, two Cys
      His repeats metal binding motifs of Tmac1p, one in the 354-369C terminus and one
      in the 475-490C terminus were also present in Mac1p. A deletion mutant of Tmac1
      was hypersensitive to the copper starvation and showed poor growth. Subsequently,
      the function was recovered by the gene complementation experiment. Furthermore,
      the Tmac1 gene fully complemented growth defects of yeast DeltaMac1 mutant. The
      expression of Tmac1p was activated at low concentration of copper and depressed
      when the concentration of copper excess 1mM. Furthermore, the fluorescence
      intensity enhanced at copper starvation and decreased under copper excess by
      fusion the eGFP to the Tmac1p. It proved that the expression of Mac1p was exactly
      regulated by copper concentration, because eGFP and Mac1p were expressed under
      the control of the same one promoter. We also cloned a gene named Tctr3 with
      bioinformatics. With a series of experiments, we proved it was the target gene of
      Tmac1. To sum up, Tmac1 may encode a transcriptional activator regulated high
      affinity copper transport in T. reesei.

PMID- 22397975
TI  - Mortality after elective colon resection: the search for outcomes that define
      quality in surgical practice.
AB  - BACKGROUND: Process measures constitute the focal point of surgical quality
      studies. High levels of compliance with such processes have not correlated with
      improved outcomes. Wide ranges of reported hospital death rates led us to
      hypothesize that survival after elective colon resection would be a legitimate
      outcomes measure for quality of surgical practice. STUDY DESIGN: We studied risk
      adjusted hospital mortality rates of 85,260 patients in teaching hospitals as
      reported to the University HealthSystem Consortium (UHC) January 1, 2005 to March
      31, 2011. Data were analyzed by institution and surgeon (deidentified). There
      were 34,504 patients from the HealthCare Utilization Project (HCUP, 2007-2008),
      who provided a comparison group for nonteaching hospitals. Surgeons with less
      than 1 year of reported data were excluded. RESULTS: Elective colon resection
      mortality rates were densely concentrated around 1.56% for teaching hospitals and
      at 1.08% for defined surgeons. HCUP data demonstrated a 1.38% nonteaching
      hospital mortality rate. Neither hospital nor surgeon volume were determinants of
      mortality, and lower volume entities displayed the widest mortality variations.
      Among 193 teaching hospitals, there were 6 outliers (4.1%), defined as >2
      standard deviations (SDs) above the mean. Similarly, 32 of 681 individual
      surgeons (4.7%) had a risk-adjusted hospital mortality rate >2SDs above the mean.
      CONCLUSIONS: Elective colon resection is a safe procedure in both teaching
      hospitals and nonteaching hospitals, with an impressively homogenous mean
      mortality rate of 1.56% in teaching hospitals, and 1.38% in nonteaching
      hospitals. We reject our original hypothesis because the data do not sufficiently
      discriminate to permit the use of death after elective colon resection as a
      differentiating quality measure; however, the data do identify individual poor
      performers. Poor performing institutions/surgeons should seek extramural guidance
      to improve their outcomes or discontinue performing such operations.

PMID- 22397976
TI  - Acute care surgery: impact on practice and economics of elective surgeons.
AB  - BACKGROUND: The creation of an acute care surgery service provides a rich
      operative experience for acute care surgeons. Elective surgeons typically have
      concerns about whether their practice volume will be restored with elective
      cases. Acute care surgery has financial implications for both groups. The aim of
      this project is to examine the impact in terms of work relative value units
      (wRVUs), collections, and cases in both groups with creation of an acute care
      surgery service at our institution. STUDY DESIGN: Work RVUs, collections, and
      case volume were examined from departmental records for 2 groups before and after
      acute care surgery service creation. The service began on September 1, 2008.
      Before this time, emergency surgical consults went to the general surgeon on
      call. After this date, all emergency consults were seen by acute care surgeons.
      RESULTS: The number of operations performed by the acute care surgery group
      increased significantly when the mean of the 2 years after institution of acute
      care surgery were compared with the mean of the 2 years preceding the service
      creation (1,639 vs 790/year; p = 0.007). There was no change in total operations
      done by the elective surgery group (2,763 vs 2,496/year: p = 0.13). Elective
      caseload, however, did increase by 23% in the elective surgery group. In the
      acute care surgery group, wRVUs increased by 140% and elective surgery group
      wRVUs decreased by 8%. Collections increased in both groups (acute care surgery
      129%, elective surgery 7%) and the combined collections of the groups increased
      by $2,138,00 in the year after service creation. CONCLUSIONS: Acute care surgery
      service creation took emergency business from the elective surgery group, but
      this was almost immediately replaced with elective cases. This resulted in higher
      collections for both groups and a resultant significant increase in collections
      in aggregate.

PMID- 22397978
TI  - Chilling curves for Piaractus mesopotamicus (Holmberg, 1887) embryos stored at -8
      degrees C.
AB  - The present study investigates the effect of different slow chilling curves on
      the storage of pacu (Piaractus mesopotamicus) embryos submitted to chilling at -8
      degrees C. Embryos at the blastopore closure stage were divided into two groups:
      G1 - embryos exposed to cryoprotectant solution containing methanol (10%) and
      sucrose (0.5 M), treated as follows: (T1) taken directly from room temperature to
      the refrigerator without being submitted to the curve; (T2) chilling curve of 0.5
      degrees C/min; and (T3) chilling curve of 1 degrees C/min; and G2 - the
      cryoprotectant solution alone was submitted to these same temperatures, receiving
      the embryos only after temperature had decreased, corresponding to treatments T4,
      T5 and T6, respectively. Treatments were kept at -8 degrees C for a period of 6
      h. Embryo development was evaluated for each treatment, with six replicates in an
      entirely randomized design. Survival among embryos not submitted to refrigeration
      was 94.3 +/- 8.05%. Percentage of total larvae (TL) and addled eggs (AE) did not
      differ statistically between the groups, although percentage of swimming larvae
      (SL) exhibited higher values in G1 for the 1 degrees C/min curve. Furthermore,
      when comparing the three chilling curves, a decrease of 1 degrees C/min resulted
      in the highest TL percentage (90.85%), followed by the 0.5 degrees C/min curve
      (78.52%). Thus, the use of 1 degrees C/min chilling curves is recommended for P.
      mesopotamicus embryos stored for 6 h at -8 degrees C.

PMID- 22397979
TI  - [Denosumab-induced severe hypocalcemia].

PMID- 22397977
TI  - Total pancreatectomy and islet autotransplantation for chronic pancreatitis.
AB  - BACKGROUND: Total pancreatectomy (TP) with intraportal islet autotransplantation
      (IAT) can relieve pain and preserve beta-cell mass in patients with chronic
      pancreatitis (CP) when other therapies fail. We report on a >30-year single
      center series. STUDY DESIGN: Four hundred and nine patients (including 53
      children, 5 to 18 years) with CP underwent TP-IAT from February 1977 to September
      2011 (etiology: idiopathic, 41%; Sphincter of Oddi dysfunction/biliary, 9%;
      genetic, 14%; divisum, 17%; alcohol, 7%; and other, 12%; mean age was 35.3 years,
      74% were female; 21% has earlier operations, including 9% Puestow procedure, 6%
      Whipple, 7% distal pancreatectomy, and 2% other). Islet function was classified
      as insulin independent for those on no insulin; partial, if known C-peptide
      positive or euglycemic on once-daily insulin; and insulin dependent if on
      standard basal-bolus diabetic regimen. A 36-item Short Form (SF-36) survey for
      quality of life was completed by patients before and in serial follow-up since
      2007, with an integrated survey that was added in 2008. RESULTS: Actuarial
      patient survival post TP-IAT was 96% in adults and 98% in children (1 year) and
      89% and 98% (5 years). Complications requiring relaparotomy occurred in 15.9% and
      bleeding (9.5%) was the most common complication. IAT function was achieved in
      90% (C-peptide >0.6 ng/mL). At 3 years, 30% were insulin independent (25% in
      adults, 55% in children) and 33% had partial function. Mean hemoglobin A1c was
      <7.0% in 82%. Earlier pancreas surgery lowered islet yield (2,712 vs 4,077/kg; p
      = 0.003). Islet yield (<2,500/kg [36%]; 2,501 to 5,000/kg [39%]; >5,000/kg [24%])
      correlated with degree of function with insulin-independent rates at 3 years of
      12%, 22%, and 72%, and rates of partial function 33%, 62%, and 24%. All patients
      had pain before TP-IAT and nearly all were on daily narcotics. After TP-IAT, 85%
      had pain improvement. By 2 years, 59% had ceased narcotics. All children were on
      narcotics before, 39% at follow-up; pain improved in 94%; and 67% became pain
      free. In the SF-36 survey, there was significant improvement from baseline in all
      dimensions, including the Physical and Mental Component Summaries (p < 0.01),
      whether on narcotics or not. CONCLUSIONS: TP can ameliorate pain and improve
      quality of life in otherwise refractory CP patients, even if narcotic withdrawal
      is delayed or incomplete because of earlier long-term use. IAT preserves
      meaningful islet function in most patients and substantial islet function in more
      than two thirds of patients, with insulin independence occurring in one quarter
      of adults and half the children.

PMID- 22397980
TI  - [Gardener pupil].

PMID- 22397981
TI  - [Echocardiography in internal medicine].

PMID- 22397982
TI  - [Anemia in heart failure: its usefulness as prognosis or comorbidity marker:
      GESAIC-2 study].
AB  - BACKGROUND AND OBJECTIVE: To assess the prognosis and etiology of anemia in heart
      failure (HF). PATIENTS AND METHODS: Prospective multicenter cohort of HF after
      one year of hospitalization. RESULTS: A total of 57 (27%) of the 211 patients
      died and 115 (67.8%) were readmitted. Mortality was higher in the group with
      anemia (31.8%) without statistical significance (P=.09), except for refractory HF
      mortality (P=.013). Predictors of HF mortality included Barthel index (hazard
      ratio [HR] 0.97, CI 95% 0.96 to 0.98) and serum creatinine at discharge (HR 2.28,
      95% CI 1.51 to 3.45). For reentry, the Charlson index (OR 1.16, CI 95% 0.98 to
      1.38), treatment with calcium channel blockers (OR 0.29, 95% CI 0.1 to 0.84) and
      not being treated with digoxin (OR 2.33, CI 95% 1.09 to 4.97), the latter with
      the greatest influence on readmission for HF (OR 3.07, CI 95% 1.39 to 6.79),
      along with not being a HF debut (OR 2.8, CI 95% 1.45 to 5.39). CONCLUSIONS:
      Anemia is an increased risk of mortality due to refractory HF, but not for
      readmission within the first year after an acute event.

PMID- 22397983
TI  - [Hyponatremia: the ignored companion].

PMID- 22397984
TI  - Translation initiation factor eIF4E is a target for tumor cell
      radiosensitization.
AB  - A core component in the cellular response to radiation occurs at the level of
      translational control of gene expression. Because a critical element in
      translation control is the availability of the initiation factor eIF4E, which
      selectively enhances the cap-dependent translation of mRNAs, we investigated a
      regulatory role for eIF4E in cellular radiosensitivity. eIF4E silencing enhanced
      the radiosensitivity of tumor cell lines but not normal cells. Similarly,
      pharmacologic inhibition of eIF4E with ribavirin also enhanced tumor cell
      radiosensitivity. eIF4E attenuation did not affect cell-cycle phase distribution
      or radiation-induced apoptosis, but it delayed the dispersion of radiation
      induced gammaH2AX foci and increased the frequency of radiation-induced mitotic
      catastrophe. Radiation did not affect 4E-BP1 phosphorylation or cap-complex
      formation but it increased eIF4E binding to more than 1,000 unique transcripts
      including many implicated in DNA replication, recombination, and repair. Taken
      together, our findings suggest that eIF4E represents a logical therapeutic target
      to increase tumor cell radiosensitivity.

PMID- 22397985
TI  - Augmented mitral valve leaflet area decreases leaflet stress: a finite element
      simulation.
AB  - BACKGROUND: Using human mitral valve (MV) models derived from three-dimensional
      echocardiography, finite element analysis was used to predict mechanical leaflet
      and chordal stress. Subsequently, valve geometries were altered to examine the
      effects on stresses of the following: (1) varying coaptation area; (2) varying
      noncoapted leaflet tissue area; and (3) varying interleaflet coefficient of
      friction (MU). METHODS: Three human MV models were loaded with a transvalvular
      pressure of 80 mm Hg using finite element analysis. Initially leaflet coaptation
      was set to 10%, 50%, or 100% of actual coaptation length to test the influence of
      coaptation length on stress distribution. Next, leaflet surface areas were
      augmented by 1% overall and by 2% in the noncoapted "belly" region to test the
      influence of increased leaflet billowing without changing the gross geometry of
      the MV. Finally, the coefficient of friction between the coapted leaflets was set
      to MU = 0, 0.05, or 0.3, to assess the influence of friction on MV function.
      RESULTS: Leaflet coaptation length did not affect stress distribution in either
      the coapted or noncoapted leaflet regions; peak leaflet stress was 0.36 +/- 0.17
      MPa at 100%, 0.35 +/- 0.14 MPa at 50%, and 0.35 +/- 0.15 MPa at 10% coaptation
      lengths (p = 0.85). Similarly, coaptation length did not affect peak chordal
      tension (p = 0.74). Increasing the noncoapted leaflet area decreased the peak
      valvular stresses by 5 +/- 2% (p = 0.02). Varying the coefficient of friction
      between leaflets did not alter leaflet or chordal stress distribution (p = 0.18).
      CONCLUSIONS: Redundant MV leaflet tissue reduces mechanical stress on the
      noncoapted leaflets; the extent of coaptation or frictional interleaflet
      interaction does not independently influence leaflet stresses. Repair techniques
      that increase or preserve noncoapted leaflet area may decrease mechanical
      stresses and thereby enhance repair durability.

PMID- 22397986
TI  - Chronic postthoracotomy pain and health-related quality of life.
AB  - BACKGROUND: Pain after thoracotomy is common. The objective of this study was to
      assess whether pain 3 months postthoracotomy negatively impacts quality of life.
      METHODS: One hundred ten patients were prospectively assessed using the Medical
      Outcomes Study 36-Item Short Form Health Survey before and 3 months after
      elective thoracotomy. Pain and medication use were evaluated by questionnaire.
      Patients experiencing pain at 3 months were compared with patients who did not
      have postthoracotomy pain. RESULTS: Seventy-five patients (68%) had pain 3 months
      postthoracotomy; 12 patients (11%) rated their average pain greater than 3 (out
      of 10). Eighteen (16%) patients required opioid analgesics. The pain group
      reported lower SF-36 scores in physical functioning (p = 0.049), bodily pain (p =
      0.0002), and vitality (p = 0.044). There were no other significant differences in
      any SF-36 scale between the pain and non-pain groups. CONCLUSIONS: Pain is
      commonly reported at 3 months after elective thoracotomy but is generally mild,
      shows improvement with time, and does not usually require opioid analgesics.
      Patients who experience postthoracotomy pain at 3 months are at risk for
      significantly decreased physical functioning and vitality, but are not at risk
      for significantly decreased social, emotional, or mental health functioning
      compared with patients who do not experience postthoracotomy pain at 3 months.

PMID- 22397987
TI  - Closed suction drainage improves clinical outcome in patients undergoing
      endoscopic vein harvesting for coronary artery bypass grafting.
AB  - BACKGROUND: Endoscopic vein harvesting (EVH) is a widely accepted technique for
      coronary artery bypass grafting, with well-reported benefits. However, EVH is
      associated with severe hematoma formation at incision sites, resulting in
      postoperative pain. We hypothesized that the use of a leg wound drain at the
      incision site may reduce these comorbidities. METHODS: One hundred consecutive
      patients were prospectively randomly allocated into two groups of 50: group 1
      with leg wound drains, and group 2 without drains. Group 1 patients underwent EVH
      followed by closure with a size 10 high vacuum leg wound drain (20 kPa), whereas
      group 2 underwent EVH followed by closure without a leg wound drain. Patients
      were assessed for postoperative pain, wound infection, and satisfaction using
      validated scoring systems immediately after surgery. RESULTS: Pain at rest (p <
      0.001) and with movement (p < 0.001), incidence of hematoma (p < 0.001), and
      patient satisfaction (p < 0.001) were significantly improved in the drain group
      at days 1 to 7 and remained significant at week 6 after surgery. Interestingly,
      the use of antibiotics (6% versus 24%, p = 0.012) and the number of general
      practitioner visits (6% versus 26%, p = 0.012) were lower in the drain group
      compared with the no-drain group. However, there were no differences in the
      length of hospital stay between the two groups after surgery. CONCLUSIONS: Our
      findings indicate that the use of a high vacuum leg drain after EVH for long
      saphenous vein is of clear therapeutic benefit in the early postoperative period.
      We also report that this technique may reduce antibiotic administration and
      general practitioner visits after patient discharge.

PMID- 22397988
TI  - Sequestration of PDC-109 protein improves freezability of crossbred bull
      spermatozoa.
AB  - A study was carried out to assess the effect of sequestration of PDC-109 protein,
      a majority constituent of heparin binding proteins (HBP) of seminal plasma, on
      freezability and in vitro fertilizing ability of crossbred bull spermatozoa after
      cryopreservation. The study consisted of isolation and characterization of PDC
      109 protein to raise anti-sera against it in rabbits. Following which, raised
      antibodies against PDC-109 protein was quantitated and coated in tubes used for
      collection of ejaculates. Semen ejaculates thus collected were cryopreserved
      using EYTG extender. Physico-morphological characteristics, viz. motility,
      viability, acrosomal integrity and HOS response as an indicator of freezability
      of cryopreserved spermatozoa were determined at pre freeze as well as post thaw
      stage. At pre freeze stage, a significant (p<0.05) improvement in viability
      (83.83 +/- 2.18 vs 75.17 +/- 2.42) and acrosome integrity (81.33 +/- 2.38 vs
      72.83 +/- 2.39) in antibodies treated group than control was observed. Similarly,
      increase in HOS responsive spermatozoa was highly significant (p<0.01) than
      control (78.83 +/- 1.69 vs 67.5 +/- 1.75). At post thaw stage, significant
      (p<0.05) improvement in viability (69.50 +/- 2.16 vs 60.33 +/- 2.19) and HOS
      responsive spermatozoa (68.67 +/- 1.62 vs 58.50 +/- 1.32) and highly significant
      (p<0.01) increase in individual motility (56.17 +/- 1.83 vs 47.00 +/- 1.86) and
      acrosome integrity (75.17 +/- 2.38 vs 61.83 +/- 2.1) was observed in antibodies
      treated group when compared to control was observed. The results from the study
      revealed that sequestration of PDC-109 protein from semen samples leads to
      significant improvement in pre-freeze and post-thaw values of above parameters in
      cryopreserved spermatozoa. It is thus concluded that sequestration of PDC-109
      protein from ejaculates improves freezability of crossbred bull spermatozoa.

PMID- 22397990
TI  - ICRP Publication 114: Environmental Protection: Transfer Parameters for Reference
      Animals and Plants.

PMID- 22397989
TI  - Determinants of physicians' technology acceptance for e-health in ambulatory
      care.
AB  - BACKGROUND: Germany is introducing a nation-wide telemedicine infrastructure that
      enables electronic health services. The project is facing massive resistance from
      German physicians, which has led to a delay of more than five years. Little is
      known about the actual burdens and drivers for adoption of e-health innovations
      by physicians. OBJECTIVE: Based on a quantitative study of German physicians who
      participated in the national testbed for telemedicine, this article extends
      existing technology acceptance models (TAM) for electronic health (e-health) in
      ambulatory care settings and elaborates on determinants of importance to
      physicians in their decision to use e-health applications. METHODS: This study
      explores the opinions, attitudes, and knowledge of physicians in ambulatory care
      to find drivers for technology acceptance in terms of information technology (IT)
      utilization, process and security orientation, standardization, communication,
      documentation and general working patterns. We identified variables within the
      TAM constructs used in e-health research that have the strongest evidence to
      determine the intention to use e-health applications. RESULTS: The partial least
      squares (PLS) regression model from data of 117 physicians showed that the
      perceived importance of standardization and the perceived importance of the
      current IT utilization (p<0.01) were the most significant drivers for accepting
      electronic health services (EHS) in their practice. Significant influence
      (p<0.05) was shown for the perceived importance of information security and
      process orientation as well as the documentation intensity and the e-health
      related knowledge. CONCLUSIONS: This study extends work gleaned from technology
      acceptance studies in healthcare by investigating factors which influence
      perceived usefulness and perceived ease of use of e-health services. Based on
      these empirical findings, we derive implications for the design and introduction
      of e-health services including suggestions for introducing the topic to
      physicians in ambulatory care and incentive structures for using e-health.

PMID- 22397991
TI  - New connections between splicing and human disease.
AB  - The removal by splicing of introns from the primary transcripts of most mammalian
      genes is an essential step in gene expression. Splicing is performed by large,
      complex ribonucleoprotein particles termed spliceosomes. Mammals contain two
      types that splice out mutually exclusive types of introns. However, the role of
      the minor spliceosome has been poorly studied. Recent reports have now shown that
      mutations in one minor spliceosomal snRNA, U4atac, are linked to a rare autosomal
      recessive developmental defect. In addition, very exciting recent results of
      exome deep-sequencing have found that recurrent, somatic, heterozygous mutations
      of other splicing factors occur at high frequencies in particular cancers and pre
      cancerous conditions, suggesting that alterations in the core splicing machinery
      can contribute to tumorigenesis. Mis-splicing of crucial genes may underlie the
      pathologies of all of these diseases. Identifying these genes and understanding
      the mechanisms involved in their mis-splicing may lead to advancements in
      diagnosis and treatment.

PMID- 22397992
TI  - Activity of Matricaria chamomilla essential oil against anisakiasis.
AB  - The increase in diagnosed cases of anisakiasis and the virtual absence of
      effective treatments have prompted the search for new active compounds against
      Anisakis L(3) larvae. The biocidal efficacy against different pathogens shown by
      various essential oils (EO) led us to study the Matricaria chamomilla EO and two
      of its main components (chamazulene and alpha-bisabolol) against the L(3) larvae
      of Anisakis type I. The activity of M. chamomilla EO, chamazulene and alpha
      bisabolol was established by in vitro and in vivo experiments. The EO (125MUg/ml)
      caused the death of all nematodes, which showed cuticle changes and intestinal
      wall rupture. In the in vivo assays, only 2.2%+/-1.8 of infected rats treated
      with M. chamomilla EO showed gastric wall lesions in comparison to 93.3%+/-3.9 of
      control. Chamazulene was ineffective, while alpha-bisabolol showed a high
      activity to that of the EO in vitro tests but proved less active in vivo. These
      findings suggest that the larvicidal activity may result from the synergistic
      action of different compounds of M. chamomilla EO. Neither of the tested products
      induces irritative damage in the intestinal tissues. In conclusion, M. chamomilla
      EO is a good candidate for further investigation as a biocidal agent against
      Anisakis type I.

PMID- 22397993
TI  - Diallyl sulfide, diallyl disulfide and diallyl trisulfide affect drug resistant
      gene expression in colo 205 human colon cancer cells in vitro and in vivo.
AB  - To elevate chemo-resistance of human cancer cells is a major obstacle in the
      treatment and management of malignant cancers. Diallyl sulfide (DAS), diallyl
      disulfide (DADS) and diallyl trisulfide (DATS) are presented in the Alliaceae
      family particularly in garlic. Although DAS, DADS and DATS have been shown to
      exhibit anticancer activities, there is little information on effects of these
      compounds on drug resistant genes in human colon cancer cells in vitro and in
      vivo. Herein, we are the first to show that DAS, DADS and DATS at 25 MUM for 24-h
      and 48-h incubations promoted expression of drug resistant genes in colo 205
      human colon cancer cells. In vitro experiments indicated that DATS promoted gene
      expression of multidrug resistant 1 (Mdr1) (p<0.05), and DAS and DADS promoted
      MRP3 gene expression and DATS alone stimulated gene expression of multidrug
      resistance-associated protein-1 (MRP1) (p<0.05) in colo 205 cells. In vivo
      studies demonstrated that DADS and DATS induced Mdr1 and MRP1 gene expression
      (p<0.05). DADS promoted MRP3 gene expression (p<0.05) as well as DADS and DATS
      increased MRP4 and MRP6 gene expression (p<0.05) in the colo 205 xenograft mice.
      Based on our in vitro and in vivo results, diallyl polysulfides (DAS, DADS and
      DATS) affected the gene expression of the multidrug resistance in colo 205 human
      colon cancer cells in vitro and in vivo.

PMID- 22397994
TI  - Neobavaisoflavone stimulates osteogenesis via p38-mediated up-regulation of
      transcription factors and osteoid genes expression in MC3T3-E1 cells.
AB  - Neobavaisoflavone (NBIF) is an isoflavone isolated from Psoralea corylifolia L, a
      plant claimed to have osteogenic activity and used to treat bone fractures,
      osteomalacia and osteoporosis. The present results showed that NBIF concentration
      dependently promoted osteogenesis in MC3T3-E1cells, demonstrated by notable
      enhancement of alkaline phosphatase (ALP) activity, increase of bone-specific
      matrix proteins expression including type I collagen (Col-I), osteocalcin (OCN)
      and bone sialoprotein (BSP), and formation of bone nodules. However, cell
      proliferation in the presence of NBIF was not affected. Results also demonstrated
      that NBIF up-regulated the expression of runt-related transcription factor 2
      (Runx2) and Osterix (Osx), the bone-specific transcription factors participating
      in regulation of bone marker genes expression. Application of p38 inhibitor
      SB203580 repressed not only NBIF-induced activation of ALP, the expression of Col
      I, OCN and BSP, but also the matrix proteins mineralization. Western blot
      analysis further revealed that NBIF increased the phosphorylated level of p38
      concentration-dependently. Additionally, inhibition of p38 abolished the
      stimulatory effect of NBIF on the expression of Runx2 and Osx. Taken together,
      the osteogenic activity of NBIF might probably act through activation of p38
      dependent signaling pathway to up-regulate the mRNA levels of Runx2 and Osx then
      stimulate bone matrix proteins expression. The beneficial effect of NBIF on
      mineralization demonstrated that NBIF represented as an active component existed
      in P. corylifolia and might be a potential anabolic agent to treat bone loss
      associated diseases.

PMID- 22397995
TI  - Non-insulin dependent anti-diabetic activity of (2S, 3R, 4S) 4-hydroxyisoleucine
      of fenugreek (Trigonella foenum graecum) in streptozotocin-induced type I
      diabetic rats.
AB  - The seeds of fenugreek, Trigonella foenum graecum, commonly used as a spice in
      Middle Eastern countries and widely used in south Asia and Europe, are known to
      have anti-diabetic properties. They contain an unusual amino acid (2S, 3R, 4S) 4
      hydroxyisoleucine (4HO-Ile), so far found only in fenugreek, which has anti
      diabetic properties of enhancing insulin secretion under hyperglycaemic
      conditions, and increasing insulin sensitivity. Here we describe for the first
      time the anti-diabetic activity of 4HO-Ile in a model of type I diabetes,
      streptozotocin-treated rats, where levels of insulin are much reduced, by 65%,
      compared to normal animals. Treatment of diabetic rats with daily doses of 4HO
      Ile at 50 mg/kg/day for four weeks could reduce plasma glucose in the diabetic
      group. Moreover the high levels of lipids (cholesterol, HDL, LDL and
      triglycerides) and uric acid in the diabetic rats, could be restored to levels
      found in non-diabetic controls by the treatment with 4HO-Ile. These results
      demonstrate that 4HO-Ile has significant anti-diabetic activities that are
      independent of insulin and suggest the potential of 4HO-Ile as an adjunct to
      diabetes treatment and for type 1 as well as type 2 diabetes.

PMID- 22397996
TI  - Induction of apoptosis against cancer cell lines by four ascomycetes (endophytes)
      from Malaysian rainforest.
AB  - Endophytic fungi have been shown to be a promising source of biologically active
      natural products. In the present study, extracts of four endophytic fungi
      isolated from plants of the National Park, Pahang were evaluated for their
      cytotoxic activity and the nature of their active compounds determined. Those
      extracts exhibiting activity with IC(50) values less than 17 MUg/ml against
      HCT116, MCF-7 and K562 cell lines were shown to induce apoptosis in these cell
      lines. Molecular analysis, based on sequences of the rDNA internal transcribed
      spacers ITS1 and ITS4, revealed all four endophytic fungi to be ascomycetes:
      three sordariomycetes and a dothideomycete. Six known compounds, cytochalasin J,
      dechlorogriseofulvin, demethylharzianic-acid, griseofulvin, harzianic acid and 2
      hexylidene-3-methyl-succinic acid were identified from a rapid dereplication
      technique for fungal metabolites using an in-house UV library. The results from
      the present study suggest the potential of endophytic fungi as cytotoxic agents,
      and there is an indication that the isolates contain bioactive compounds that
      mainly kill cancer cells by apoptosis.

PMID- 22397997
TI  - The ICU patient room: views and meanings as experienced by the next of kin: a
      phenomenological hermeneutical study.
AB  - The rooms in Intensive Care Units are considered as high-tech environments and
      believed to affect recovery process and wellbeing of patients. Moreover, the
      design and interiors affect the interplay between the patient and the next of
      kin. OBJECTIVE: The aim of this study was to describe and interpret the meanings
      of the intensive care patient room as experienced by next of kin. DESIGN: Next of
      kin (n=14) from two different intensive care units participated. Data were
      collected through photo-voice and analysed using a phenomenological hermeneutical
      method. RESULTS: Three major themes emerged; dwelling in the room and time,
      becoming at home and extension of the room. The results show that the room is
      perceived as a lived and extended place and space. The design, interiors and
      furnishing in the patient room are fundamental in shaping the next of kin's
      experiences in the room and affect wellbeing. CONCLUSIONS: How intensive care
      patient rooms are designed, the place given to next of kin and the way they are
      received in the room are decisive for the support given to the loved one. Simple
      interventions can make the patient room a more healing environment.

PMID- 22397998
TI  - Canadian guidelines for the evidence-based treatment of tic disorders.

PMID- 22397999
TI  - Canadian guidelines for the evidence-based treatment of tic disorders:
      pharmacotherapy.
AB  - This article seeks to provide the practising clinician with guidance on the
      pharmacological management of tic disorders in children and adults. We performed
      a systematic review of the literature on the treatment of tic disorders. A multi
      institutional group of 14 experts in psychiatry, child psychiatry, neurology,
      pediatrics, and psychology engaged in a consensus meeting. The evidence was
      presented and discussed, and nominal group techniques were employed to arrive at
      consensus on recommendations. A strong recommendation is made when the benefits
      of treatment clearly outweigh the risks and burdens, and can apply to most
      patients in most circumstances without reservation. With a weak recommendation,
      the benefits, risks, and burdens are more closely balanced, and the best action
      may differ depending on the circumstances. Based on these principles, weak
      recommendations were made for the use of pimozide, haloperidol, fluphenazine,
      metoclopramide (children only), risperidone, aripiprazole, olanzapine,
      quetiapine, ziprasidone, topiramate, baclofen (children only), botulinum toxin
      injections, tetrabenazine, and cannabinoids (adults only). Strong recommendations
      were made for the use of clonidine and guanfacine (children only). While the
      evidence supports the efficacy of many of the antipsychotics for the treatment of
      tics, the high rates of side effects associated with these medications resulted
      in only weak recommendations for these drugs. In situations where tics are not
      severe or disabling, the use of a medication with only a weak recommendation is
      not warranted. However, when tics are more distressing and interfering, the need
      for tic suppression to improve quality of life is stronger, and patients and
      clinicians may be more willing to accept the risks of pharmacotherapy.

PMID- 22398000
TI  - Canadian guidelines for the evidence-based treatment of tic disorders:
      behavioural therapy, deep brain stimulation, and transcranial magnetic
      stimulation.
AB  - This clinical guideline provides recommendations for nonpharmacological
      treatments for tic disorders. We conducted a systematic literature search for
      clinical trials on the treatment of tics. One evidence-based review (including 30
      studies) and 3 studies on behavioural interventions, 3 studies on deep brain
      stimulation (DBS), and 3 studies on transcranial magnetic stimulation (TMS) met
      our inclusion criteria. Based on this evidence, we have made strong
      recommendations for the use of habit reversal therapy and exposure and response
      prevention, preferably embedded within a supportive, psychoeducational program,
      and with the option to combine either of these approaches with pharmacotherapy.
      Although evidence exists for the efficacy of DBS, the quality of this evidence is
      poor and the risks and burdens of the procedure are finely balanced with the
      perceived benefits. Our recommendation is that this intervention continues to be
      considered an experimental treatment for severe, medically refractory tics that
      have imposed severe limitations on quality of life. We recommend that the
      procedure should only be performed within the context of research studies and by
      physicians expert in DBS programming and in the management of tics. There is no
      evidence to support the use of TMS in the treatment of tics. However, the
      procedure is associated with a low rate of known complications and could continue
      to be evaluated within research protocols. The recommendations we provide are
      based on current knowledge, and further studies may result in their revision in
      future.

PMID- 22398001
TI  - Responses to mental health stigma questions: the importance of social
      desirability and data collection method.
AB  - OBJECTIVE: To evaluate the impact on the general public of England's Time to
      Change program to reduce mental health-related stigma and discrimination using
      newly developed measures of knowledge and intended behaviour regarding people
      with mental health problems, and an established attitudes scale, and to
      investigate whether social desirability affects responses to the new measures and
      test whether this varies according to data collection method. METHOD: The Mental
      Health Knowledge Schedule (MAKS) and Reported and Intended Behaviour Scale (RIBS)
      were administered together with the 13-item version of the Marlowe-Crowne Social
      Desirability Scale to 2 samples (each n = 196) drawn from the Time to Change mass
      media campaign target group; one group was interviewed face to face, while the
      other completed the measures as an online survey. RESULTS: After controlling for
      other covariates, interaction terms between collection method and social
      desirability were positive for each instrument. The social desirability score was
      associated with the RIBS score in the face-to-face group only (beta = 0.35, 95%
      CI 0.14 to 0.57), but not with the MAKS score in either group; however, MAKS
      scores were more likely to be positive when data were collected face to face
      (beta = 1.53, 95% CI 0.74 to 2.32). CONCLUSIONS: Behavioural intentions toward
      people with mental health problems may be better assessed using online self
      complete methods than in-person interviews. The effect of face-to-face
      interviewing on knowledge requires further investigation.

PMID- 22398002
TI  - Patterns of depression and treatment in pregnant and postpartum women.
AB  - OBJECTIVE: To determine the course of depression and the effects of treatment
      during pregnancy and into the postpartum period. METHOD: This is a longitudinal
      study of a community sample of 649 pregnant women who were assessed in early
      pregnancy (17.4 +/- 4.9 weeks), late pregnancy (30.6 +/- 2.7 weeks), and
      postpartum (4.2 +/- 2.1 weeks) with the Edinburgh Postnatal Depression Scale
      (EPDS). Women who scored 12 or more on the EPDS were encouraged to seek
      assessment and treatment. We used generalized estimating equation modelling to
      determine the predicted mean depression scores, taking age, ethnicity, history of
      depression, and previous and present treatment status into account. RESULTS: The
      unadjusted prevalence of depression (EPDS >= 12) was 14.1% (n = 91) in early
      pregnancy, 10.4% (n = 62) in late pregnancy, and 8.1% (n = 48) postpartum. Twelve
      per cent of women were engaged in treatment. The predicted mean EPDS score
      decreased over the course of the pregnancy into the postpartum period, most
      significantly when women were engaged in counselling or taking psychotropic
      medication. Counselling was the more common method of treatment during pregnancy
      and medication in the postpartum period. Women who were depressed and untreated
      were more likely to be younger, more stressed, have less support, have a history
      of depression, and use alcohol. CONCLUSIONS: We confirm that depressive symptoms
      improve over the course of the pregnancy into the postpartum period, particularly
      for women who receive treatment. Our study is unique as it takes the history of
      depression, present and past treatment status, and the longitudinal nature of the
      data into account.

PMID- 22398003
TI  - Smoking, but not malnutrition, influences promoter-specific DNA methylation of
      the proopiomelanocortin gene in patients with and without anorexia nervosa.
AB  - OBJECTIVE: Our pilot study evaluates the impact of environmental factors, such as
      nutrition and smoking status, on epigenetic patterns in a disease-associated
      gene. METHOD: We measured the effects of malnutrition and cigarette smoking on
      proopiomelanocortin (POMC) promoter-specific DNA methylation in female patients
      with and without anorexia nervosa (AN). POMC and its derived peptides (alpha
      melanocyte stimulating hormone and adrenocorticotropic hormone) are implicated in
      stress and feeding response. Promoter-specific DNA methylation of the POMC gene
      was determined in peripheral blood mononuclear cells of 54 healthy female control
      subjects, 40 underweight patients with AN, and 21 weight-restored patients with
      AN using bisulfite sequencing. Malnutrition was characterized by plasma leptin.
      RESULTS: POMC promoter-specific DNA methylation was not affected by diagnosis or
      nutritional status but significantly negatively associated with cigarette
      smoking. CONCLUSIONS: Although malnutrition may be expected to reduce DNA
      methylation through its effects on one-carbon metabolism, our negative results
      are in line with several in vitro and clinical studies that did not show a direct
      relation between gene-specific DNA methylation and folate levels. In contrast,
      smoking has been repeatedly reported to alter DNA methylation of specific genes
      and should be controlled for in future epigenetic studies.

PMID- 22398004
TI  - Disgust recognition in obsessive-compulsive disorder: diagnostic comparisons and
      posttreatment effects.
AB  - OBJECTIVE: To examine whether disgust recognition deficits are present and
      specific to obsessive-compulsive disorder (OCD), and the extent to which this
      deficit, if present, can be reduced in cognitive-behavioural therapy (CBT).
      METHOD: Responses to the Pictures of Facial Affect (POFA) were examined in
      patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, diagnosed OCD (n = 20), panic disorder with agoraphobia (PDA; n = 15),
      and generalized social phobia (GSP; n = 15) and a second, independent OCD sample
      of treatment responders to CBT (n = 11). RESULTS: There were significant and
      statistically large disgust recognition differences between the OCD group and
      comparison PDA and GSP groups. However, patients with OCD treated with CBT showed
      disgust recognition scores that were equivalent to the PDA and GSP groups,
      significantly better than the untreated OCD sample, and equivalent to scores from
      the original POFA nonaffected standardization sample. CONCLUSIONS: These results
      provide support for the presence of disgust recognition impairment in OCD, and
      provide preliminary evidence that disgust recognition impairments may improve
      with treatment.

PMID- 22398005
TI  - Substances used in completed suicide by overdose in Toronto: an observational
      study of coroner's data.
AB  - OBJECTIVE: To identify the substances used by people who die from suicide by
      overdose in Toronto and to determine the correlates of specific categories of
      substances used. METHOD: Coroner's records for all cases of suicide by overdose
      in Toronto, Ontario, during a 10-year period (1998 to 2007) were examined. Data
      collected included demographic data, all substances detected, and those
      determined by the coroner to have caused death. Logistic regression analyses were
      used to examine demographic and clinical factors associated with suicide by
      different drug types. RESULTS: There were 397 documented suicides by overdose
      (mean age 49.1 years, 50% female). Most substances detected were psychotropic
      prescription medications (n = 245), followed by other prescription medications (n
      = 143) and over-the-counter (OTC) medications (n = 83). More than one-half of all
      suicides by overdose were determined to have only one specific substance as the
      cause of death (n = 206). In suicides where only one class of substance was
      present in lethal amounts, OTC medication (n = 48), opioid analgesics (n = 44),
      and tricyclic antidepressants (n = 44) were most common. CONCLUSIONS: Suicides by
      overdose involved the use of different classes of substances, including
      psychotropic prescription medication, other prescription medications, as well as
      OTC medications. Physicians and pharmacists should be aware of commonly used
      prescription and OTC medications in overdose and exercise increased vigilance in
      prescribing or dispensing them to at-risk patients.

PMID- 22398006
TI  - [Prevalence of gambling habits in Gaspesie and Iles-de-la-Madeleine in 2009].
AB  - OBJECTIF : Estimer la prevalence des habitudes aux jeux de hasard et d'argent
      (JHA), du jeu a risque (JAR) et du jeu pathologique probable (JPP) dans la region
      de la Gaspesie et des Iles-de-la-Madeleine (GIM) (Quebec). METHODE : Un sondage
      telephonique portant sur les habitudes de jeu a ete realise aupres de 1014
      adultes residents de la region de la GIM. Les participants ont ete selectionnes
      aleatoirement. L'echelle Problem Gambling Severity Index de l'Indice canadien du
      jeu excessif a servi a l'evaluation du jeu pathologique. RESULTATS : Quatre-vingt
      cinq pour cent des repondants rapportent avoir joue a un JHA au cours de l'annee
      precedente. Les activites les plus populaires sont l'achat de billets de loterie,
      la participation a des tirages et collectes de fonds, le bingo, les cartes ou
      jeux de societe en famille ou avec des amis pour de l'argent, la loterie video et
      les jeux de casino. Les taux de prevalence du JAR et du JPP s'elevent a 1,5 % et
      0,8 % respectivement. La loterie video s'avere le jeu le plus souvent identifie
      comme etant problematique, suivi des loteries instantanees et ordinaires (par
      exemple, Lotto 6/49). CONCLUSION: Les habitudes de jeu des Gaspesiens et des
      Madelinots sont similaires a celles observees chez l'ensemble des Quebecois. La
      discussion souleve entre autres la question de la validite de l'evaluation de la
      presence d'un probleme de jeu parmi les membres de l'entourage, et certaines
      perceptions a risque, dont celle qu'il est impossible de developper un probleme
      aux loteries instantanees et au bingo.

PMID- 22398007
TI  - Photon counting spectral CT: improved material decomposition with K-edge-filtered
      x-rays.
AB  - Photon counting spectral computed tomography (PCSCT) provides material selective
      CT imaging at a single CT scan and fixed tube voltage. The PCSCT data are
      acquired in several energy ranges (bins) arranged over the x-ray spectrum. The
      quasi-monoenergetic CT images are acquired in these energy bins and are used for
      material decomposition. The PCSCT exhibits inherent limitations when material
      decomposition is performed using energy bins. For effective material
      decomposition, the energy bins used for material decomposition should be
      sufficiently narrow and well separated. However, when narrow bins are used, a
      large fraction of the detected x-ray counts is lost and statistical noise is
      increased. Alternatively, the x-ray spectrum can be split into a few larger bins
      with no gap in between and all detected x-ray photons can be used for material
      decomposition. However, in this case the energy bins are too wide and not well
      separated, which results in suboptimal material decomposition. The above
      contradictory requirements can be resolved if the x-ray photons are physically
      removed from the regions of the energy spectrum between the energy bins. Such a
      selective removal can be performed using filtration of the x-ray beam by high-Z
      filter materials with appropriate positions of K-edge energies. The K-edge
      filtration of x-rays can, therefore, provide necessary gaps between the energy
      bins with no dose penalty to the patient. In the current work, we proposed using
      selective K-edge filtration of x-rays in PCSCT and performed the first
      experimental investigation of this approach. The PCSCT system included a cadmium
      zinc telluride semiconductor detector with 2 * 256 pixels and 1 * 1 mm(2) pixel
      size, and five energy bins. The CT phantom had 14 cm diameter and included
      contrast elements of iodine, gold and calcifications with clinically relevant
      concentrations. The tube voltages of 60, 90 and 120 kVp were used. K-edge filters
      based on Ba (E(k) = 37.44 keV) were used for a 60 kVp tube voltage and Gd (E(k) =
      50.24 keV) was used for the 90 and 120 kVp tube voltages, respectively. The
      material selective CT images were also acquired with conventional Al filtration
      for comparison. The half-value layers of x-ray beams after K-edge and Al
      filtration were matched. The mean entrance skin exposure was 280 mR for all tube
      voltages and filters. The contrast-to-noise ratio (CNR) in material-decomposed
      images was approximately 30%-50% higher when K-edge filters were used instead of
      Al filters. It was concluded that K-edge filtration of x-rays provides
      substantial improvement of the CNR in material-selective PCSCT. Further
      optimization of K-edge filter materials, tube voltages, detector technology and
      energy bin settings will provide even higher CNR in decomposed images.

PMID- 22398008
TI  - Apical-sparing variant of stress cardiomyopathy: Integrative analysis with
      multidetector row cardiac computed tomography in dual-energy mode.
AB  - Stress cardiomyopathy is a unique reversible cardiac syndrome that is frequently
      precipitated by a physical or emotionally stressful event and has a clinical
      presentation that is indistinguishable from a myocardial infarction. We describe
      the case of a patient with apical sparing variant of stress cardiomyopathy in
      whom dual energy cardiac CT identified characteristic regional wall motion
      abnormality without concomitant coronary artery disease and myocardial perfusion
      defects.

PMID- 22398009
TI  - Atrial isomerism: a pictorial review.
AB  - This review describes the broad spectrum of findings found in atrial isomerism,
      suggesting a sequential approach to image evaluation, and illustrates the most
      common situs disorders, for example, polysplenia and asplenia.

PMID- 22398010
TI  - Primary cardiac lymphoma diagnosed by multiphase-gated cardiac CT and CT-guided
      percutaneous trans-sternal biopsy.
AB  - We present a case of a primary cardiac B-cell lymphoma where a multiphase-gated
      cardiac CT exam helped to successfully guide trans-sternal needle biopsy to
      establish a tissue diagnosis.

PMID- 22398011
TI  - Tissue factor-driven thrombin generation and inflammation in atherosclerosis.
AB  - The transmembrane receptor tissue factor is a prominent protein expressed at
      macrophages and smooth muscle cells within human atherosclerotic lesions. While
      many coagulation proteins are detectable in atherosclerosis, a locally active
      thrombin and fibrin generating molecular machinery may be instrumental in
      manipulating cellular functions involved in atherogenesis. These include
      inflammation, angiogenesis and cell proliferation. Indeed, many experimental
      studies in mice show a correlation between hypercoagulability and increased
      atherosclerosis. In mice, the amount of atherosclerosis and/or the plaque
      phenotype, appear to be modifiable by specific anticoagulant interventions. While
      attempts to vary tissue factor level in the vasculature does not directly reduce
      plaque burden, the overexpression of tissue factor pathway inhibitor attenuates
      thrombogenicity and neo intima formation in mice. Moreover, inhibition of factor
      Xa or thrombin with novel selective agents, including rivaroxaban and dabigatran,
      inhibits inflammation associated with atherosclerosis in apoE(-/-) mice. The
      potential to modify a complex chronic disease like atherosclerosis with novel
      selective anticoagulants merits further clinical study.

PMID- 22398012
TI  - Tissue factor and cardiomyocytes.
AB  - Tissue factor, the initiator of blood coagulation, plays a major role in the
      protection of several organs against bleeding. Cardiomyocytes and fibroblasts
      constitutively express tissue factor. Besides its role for maintain cardiac
      hemostasis TF has been suggested to have several other important functions in the
      cardiac muscle. This review summarizes the different roles of TF in the heart
      with a special focus on pathological conditions.

PMID- 22398013
TI  - Murine models of thrombosis.
AB  - Manipulations of mouse vessels are difficult due to their small sizes, limiting
      the possibilities for developing clinically relevant thrombosis models. Currently
      used models of arterial and venous thrombosis have short-comings not only in
      terms of clinical relevance but also with respect to collection of data usable
      and commensurate with thrombodynamic processes. Confocal and multiphoton imaging
      systems offer continuous evaluation of more direct measures, such as fluorophore
      labeled, thrombus-targeting factors, but have been predominantly confined to
      studies in microvessels (arterioles and venules) with questionable transference
      of findings to large-vessel thrombotic activities. Going forward, we should
      select more clinically relevant models, using evaluative measures that yield
      optimal quantitative data, to refine our understanding of critical aspects of
      thrombotic processes.

PMID- 22398014
TI  - Tissue factor and thrombin in sickle cell anemia.
AB  - Sickle cell anemia is an inherited hematologic disorder associated with hemolytic
      and vaso-occlusive complications. An activation of coagulation is also a
      prominent feature of sickle cell anemia. Growing evidence indicates that
      coagulation may contribute to the inflammation and vascular injury in sickle cell
      anemia. This review focuses on tissue factor expression and its contribution to
      the activation of coagulation, thrombosis and vascular inflammation in sickle
      cell anemia.

PMID- 22398015
TI  - Regulatory mechanisms of the plasma contact system.
AB  - The plasma contact system is a proinflammatory and procoagulant protease system.
      The biochemistry of the system is well established, however, its biological
      functions are just beginning to emerge. Here, we provide a condensed overview on
      mechanisms involved in activation and regulation of the contact system. These
      recent findings will help us to better understand the role of the enigmatic
      system for health and disease.

PMID- 22398017
TI  - Phytochelatins play a key role in arsenic accumulation and tolerance in the
      aquatic macrophyte Wolffia globosa.
AB  - The rootless duckweed Wolffia globosa can accumulate and tolerate relatively
      large amounts of arsenic (As); however, the underlying mechanisms were unknown.
      W. globosa was exposed to different concentrations of arsenate with or without l
      buthionine sulphoximine (BSO), a specific inhibitor of gamma-glutamylcysteine
      synthetase. Free thiol compounds and As(III)-thiol complexes were identified and
      quantified using HPLC - high resolution ICP-MS - accurate mass ESI-MS. Without
      BSO, 74% of the As accumulated in the duckweed was complexed with phytochelatins
      (PCs), with As(III)-PC(4) and As(III)-PC(3) being the main species. BSO was taken
      up by the duckweed and partly deaminated. The BSO treatment completely suppressed
      the synthesis of PCs and the formation of As(III)-PC complexes, and also
      inhibited the reduction of arsenate to arsenite. BSO markedly decreased both As
      accumulation and As tolerance in W. globosa. The results demonstrate an important
      role of PCs in detoxifying As and enabling As accumulation in W. globosa.

PMID- 22398016
TI  - Tissue factor encryption and decryption: facts and controversies.
AB  - Tissue factor (TF)-initiated coagulation plays a critical role in both hemostasis
      and thrombosis. It is generally believed that most of the tissue factor expressed
      on cell surfaces is maintained in a cryptic, i.e., coagulantly inactive state and
      an activation step (decryption) is required for the expression of maximum TF
      procoagulant activity. However, what exactly constitutes cryptic or procoagulant
      TF, molecular differences between these two forms and mechanisms that are
      responsible for transformation from one to the other form are not entirely clear
      and remain highly controversial, thus are a matter of ongoing debate. This brief
      review discusses pertinent literature on TF encryption/decryption with specific
      emphasis on the role of membrane phospholipids and reduction/oxidation of the TF
      Cys186-Cys209 disulfide bond in regulating TF activity at cell surfaces.

PMID- 22398018
TI  - Implementation of a module for risk of ozone impacts assessment to vegetation in
      the Integrated Assessment Modelling system for the Iberian Peninsula. Evaluation
      for wheat and Holm oak.
AB  - A module to estimate risks of ozone damage to vegetation has been implemented in
      the Integrated Assessment Modelling system for the Iberian Peninsula. It was
      applied to compute three different indexes for wheat and Holm oak; daylight AOT40
      (cumulative ozone concentration over 40 ppb), cumulative ozone exposure index
      according to the Directive 2008/50/EC (AOT40-D) and POD(Y) (Phytotoxic Ozone Dose
      over a given threshold of Y nmol m(-2) s(-1)). The use of these indexes led to
      remarkable differences in spatial patterns of relative ozone risks on vegetation.
      Ozone critical levels were exceeded in most of the modelling domain and soil
      moisture content was found to have a significant impact on the results. According
      to the outputs of the model, daylight AOT40 constitutes a more conservative index
      than the AOT40-D. Additionally, flux-based estimations indicate high risk areas
      in Portugal for both wheat and Holm oak that are not identified by AOT-based
      methods.

PMID- 22398019
TI  - Prognostic factors and treatment strategies for adult head and neck soft tissue
      sarcoma.
AB  - Adult head and neck soft tissue sarcomas are rare and display a variety of
      histological types and clinical characteristics; they are also associated with a
      variety of mortality risks. The purpose of this study was to examine all patients
      treated at the Instituto Nacional de Cancerologia for head and neck sarcoma
      during a 5-year period. Fifty-one adult patients were examined and treated for
      head and neck sarcomas from 2004 to 2009. The 51 tumours were histologically re
      evaluated by expert pathologists and classified as low, intermediate or high
      grade sarcomas. A multivariate analysis was performed to evaluate the surgical
      margins, histological grades, and clinical stages as prognostic factors for the
      disease. Adult head and neck soft tissue tumours are rare, and they are
      associated with poor prognosis for patients, especially at clinical stages III
      and IV. The average survival rate after 2 years is 45%, and most of these
      patients die because of disease progression and metastases.

PMID- 22398020
TI  - Changes in the lip closing force of patients with class III malocclusion before
      and after orthognathic surgery.
AB  - The purpose of this study was to examine the changes in lip pressure before and
      after orthognathic surgery for skeletal class III patients. The subject groups
      were 32 female and 31 male patients diagnosed with mandibular prognathism and/or
      maxillary retrognathism who underwent orthognathic surgery. Control groups
      consisted of 20 women and 20 men with normal occlusion without dento-alveolar
      deformity. Maximum and minimum lip closing force was measured with Lip De Cum(r)
      for the control groups and subject groups preoperatively and 6 months
      postoperatively. The difference between the pre- and postoperative values of the
      groups was examined statistically. The maximum lip closing force in men was
      significantly larger than that in women in both the preoperative class III group
      (p=0.0330) and the control group (p=0.0097). The preoperative class III group was
      significantly smaller than the control group in maximum lip closing force in both
      men (p<0.0001) and women (p<0.0001). The postoperative maximum lip closing force
      was significantly larger than the preoperative value in both men (p=0.0037) and
      women (p=0.0273) in the Class III group. This study suggested that the maximum
      lip closing force increases after orthognathic surgery in Class III patients.

PMID- 22398021
TI  - Fibroblast growth factor-21 protects human skeletal muscle myotubes from
      palmitate-induced insulin resistance by inhibiting stress kinase and NF-kappaB.
AB  - We investigated the effects of fibroblast growth factor-21 (FGF-21) on palmitate
      induced insulin resistance in skeletal muscle myotubes. First, to determine the
      effect of FGF-21 on palmitate-induced insulin resistance, we measured 2-[N-(7
      nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose uptake and levels of
      proteins involved in insulin signaling pathways (IRS-1 and Akt) in human skeletal
      muscle myotubes (HSMMs) exposed to palmitate for 24h, and compared HSMMs exposed
      to palmitate and different doses of recombinant FGF-21. Second, to determine the
      mechanisms underlying the contribution of FGF-21 to palmitate-induced insulin
      resistance, we compared levels of proteins linked to palmitate-induced insulin
      resistance (PKC-theta, IKKalpha/beta, JNK, p38, IkappaBalpha, and NF-kappaB) in
      HSMMs exposed to palmitate and different doses of recombinant FGF-21 for 24h.
      Palmitate-reduced glucose uptake was restored by FGF-21. Palmitate inhibited
      phosphorylation of Akt and thereby impaired insulin signaling in HSMMs. FGF-21
      prevented palmitate from inhibiting the phosphorylation of Akt. These results
      indicate that FGF-21 prevented palmitate-induced insulin resistance in HSMMs.
      Palmitate activated NF-kappaB in HSMMs, thereby impairing the action of insulin
      and initiating chronic inflammation. FGF-21 inhibited palmitate-induced NF-kappaB
      activation in HSMMs. The results of the present study suggest that FGF-21
      prevents palmitate-induced insulin resistance in HSMMs by inhibiting the
      activation of stress kinase and NF-kappaB.

PMID- 22398023
TI  - Effects of cryostorage on human sperm chromatin integrity.
AB  - The integrity of sperm chromatin structure has proven to be of great importance
      for human fertility. In this study, we investigated whether sperm
      cryopreservation has an effect on nuclear DNA tertiary structure, (i.e.
      condensation), measured by aniline blue staining, in 103 male patients who
      required consultation for hypo-fertility. Sperm DNA damage was significantly
      higher in patients showing oligospermia and severe morphological abnormalities
      than in native sperm populations. Furthermore we observed that chromatin
      decondensation was related to the cryostorage technique and to the duration of
      storage. This increase in decondensation was highly significant (P < 0.01)
      immediately after cryopreservation and from 90 days of cryostorage onwards. The
      possible mechanisms involved in sperm chromatin cryoinjury and the need to
      incorporate new methods for testing sperm nuclear structure alteration into the
      routine spermiogram are discussed.

PMID- 22398024
TI  - Do we need age-specific alcohol consumption guidelines?

PMID- 22398025
TI  - Dietary long-chain polyunsaturated fatty acids upregulate expression of FADS3
      transcripts.
AB  - The fatty acid desaturase (FADS) gene family at 11q12-13.1 includes FADS1 and
      FADS2, both known to mediate biosynthesis of omega-3 and omega-6 long-chain
      polyunsaturated fatty acids (LCPUFA). FADS3 is a putative desaturase due to its
      sequence similarity with FADS1 and FADS2, but its function is unknown. We have
      previously described 7 FADS3 alternative transcripts (AT) and 1 FADS2 AT
      conserved across multiple species. This study examined the effect of dietary
      LCPUFA levels on liver FADS gene expression in vivo and in vitro, evaluated by
      qRT-PCR. Fourteen baboon neonates were randomized to three diet groups for their
      first 12 weeks of life, C: Control, no LCPUFA, L: 0.33% docosahexaenoic acid
      (DHA)/0.67% arachidonic acid (ARA) (w/w); and L3: 1.00% DHA/0.67% ARA (w/w).
      Liver FADS1 and both FADS2 transcripts were downregulated by at least 50% in the
      L3 group compared to controls. In contrast, FADS3 AT were upregulated (L3 > C),
      with four transcripts significantly upregulated by 40% or more. However, there
      was no evidence for a shift in liver fatty acids to coincide with increased FADS3
      expression. Significant upregulation of FADS3 AT was also observed in human liver
      derived HepG2 cells after DHA or ARA treatment. The PPARgamma antagonist GW9662
      prevented FADS3 upregulation, while downregulation of FADS1 and FADS2 was
      unaffected. Thus, FADS3 AT were directly upregulated by LCPUFA by a PPARgamma
      dependent mechanism unrelated to regulation of other desaturases. This opposing
      pattern and mechanism of regulation suggests a dissimilar function for FADS3 AT
      compared to other FADS gene products.

PMID- 22398026
TI  - Perceptions and experiences of parenthood and maternal health care among Latin
      American women living in Spain: a qualitative study.
AB  - OBJECTIVE: to explore the experiences and perceptions of parenthood and maternal
      health care among Latin American women living in Spain. DESIGN: an exploratory
      qualitative research using focus groups and thematic analysis of the discussion.
      SETTING AND PARTICIPANTS: three focus groups with 26 women from Bolivia and
      Ecuador and three focus groups with 24 midwives were performed in three towns in
      the Valencian Community receiving a large influx of immigrants. FINDINGS: the
      women interpreted motherhood as the role through which they achieve fulfilment
      and assumed that they were the ones who could best take care of their children.
      They perceived that men usually make decisions about sex and pregnancy and
      recognised a poor or inadequate use of contraceptive methods in planning their
      pregnancies. Women reported that it was not necessary to go as soon and as
      frequently for health examinations during pregnancy as the midwives suggested.
      The main barriers identified to health-care services were linked to insecure or
      illegal employment status, inflexible appointment timetables for prenatal
      checkups and sometimes to ignorance about how public services worked. KEY
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: empowering immigrant women is
      essential to having a long-term positive effect on their reproductive health.
      Antenatal care providers should be trained to build maternity care that is
      culturally sensitive and responds better to the health needs of different
      pregnant women and their newborns.

PMID- 22398027
TI  - An oscillatory criterion for a time delayed neural ring network model.
AB  - The effects of delays on dynamical networks and the stability analysis of time
      delayed systems have received a notable attention over the past decades. In this
      paper, the effects of delays on the oscillatory properties of a neural ring
      networks model are considered. The existence of oscillations for a specific type
      of recurrent neural network with time delays between neural interconnections is
      investigated. By using Chafee's closed orbit theory, some sufficient conditions
      for permanent oscillations are obtained. Simple and practical criteria for
      selecting the range of parameters in this network model are also derived. Among
      other things, the solutions that we provide can be applied to various activation
      functions. A few computer simulations are presented to support our analysis. The
      present study can be applied to analyze under which conditions a ring network
      could be exploited as an oscillatory pattern generator.

PMID- 22398028
TI  - Norepinephrine suppresses IFN-gamma and TNF-alpha production by murine intestinal
      intraepithelial lymphocytes via the beta1 adrenoceptor.
AB  - We examined whether norepinephrine (NE) had direct effects on cytokine production
      by murine intestinal intraepithelial lymphocytes (IELs), compared with
      splenocytes. CD3+ IELs and CD3+ splenocytes expressed alpha(1B), alpha(1D),
      alpha(2C), beta1, beta2, and beta3 adrenoceptors (ARs). NE significantly
      suppressed IFN-gamma and TNF-alpha production by IELs and splenocytes ex vivo.
      The suppressive effects of NE in IELs were reversed by beta1 AR antagonist CGP
      20712A, whereas those in splenocytes were reversed by beta2 AR antagonist
      ICI118,551. In IELs, beta1 AR agonist xamoterol mimicked the suppressive effects
      of NE. These results indicated NE regulates intestinal mucosal immune responses
      mediated by IELs via beta1 AR.

PMID- 22398029
TI  - Oxidative DNA damage and global DNA hypomethylation are related to folate
      deficiency in chromate manufacturing workers.
AB  - Exposure to hexavalent chromium [Cr (VI)] can cause DNA damage, genetic
      instability and increase the risk of cancer development. Folate deficiency
      affects DNA methylation and reduces the stability of the genetic material.
      However, the correlation between folate deficiency and DNA damage has never been
      clearly elucidated in chromate workers. In this study, we recruited one hundred
      and fifteen workers from chromate producing facilities as testing subjects and
      sixty local residents without chromium exposure history served as controls. The
      results showed an evident accumulation of Cr in peripheral red blood cells
      accompanied by a significantly decreased serum folate in chromate exposed
      workers. The decreased serum folate was associated with an increased urinary 8
      hydroxy-2'-deoxyguanosine, DNA strand breaks and global DNA hypomethylation.
      These findings suggest that chronic occupational chromate exposure could induce
      folate depletion, which may further promote DNA damages and global DNA
      hypomethylation. Adequate folate supplement may provide benefit to chromate
      sufferers in stabilization of genetic material and reduce the risk of cancer
      development.

PMID- 22398030
TI  - Metals recovering from waste printed circuit boards (WPCBs) using molten salts.
AB  - Recycling of waste electrical and electronic equipments (WEEE) has been taken
      into consideration in the literature due to the large quantity of concerned
      wastes and their hazardous contents. The situation is so critical that EU
      published European Directives imposing collection and recycling with a minimum of
      material recovery [1]. Moreover, WEEEs contain precious metals, making the
      recycling of these wastes economically interesting, but also some critical metals
      and their recycling leads to resource conservation. This paper reports on a new
      approach for recycling waste printed circuit boards (WPCBs). Molten salts and
      specifically molten KOH-NaOH eutectic is used to dissolve glasses, oxides and to
      destruct plastics present in wastes without oxidizing the most valuable metals.
      This method is efficient for recovering a copper-rich metallic fraction, which
      is, moreover, cleared of plastics and glasses. In addition, analyses of gaseous
      emission show that this method is environmentally friendly since most of the
      process gases, such as carbon monoxide and dioxide and halogens, are trapped in
      the highly basic molten salt. In other respects, under operation without oxygen,
      a large quantity of hydrogen is produced and might be used as fuel gas or as
      synthesis gas, leading to a favourable energy balance for this new process.

PMID- 22398031
TI  - Airlift bioreactor containing chitosan-immobilized Sphingobium sp. P2 for
      treatment of lubricants in wastewater.
AB  - An internal loop airlift bioreactor containing chitosan-immobilized Sphingobium
      sp. P2 was applied for the removal of automotive lubricants from emulsified
      wastewater. The chitosan-immobilized bacteria had higher lubricant removal
      efficiency than free and killed-immobilized cells because they were able to sorp
      and degrade the lubricants simultaneously. In a semi-continuous batch experiment,
      the immobilized bacteria were able to remove 80-90% of the 200 mg L(-1) total
      petroleum hydrocarbons (TPH) from both synthetic and carwash wastewater. The
      internal loop airlift bioreactor, containing 4 g L(-1) immobilized bacteria, was
      later designed and operated at 2.0 h HRT (hydraulic retention time) for over 70
      days. At a steady state, the reactor continuously removed 85+/-5% TPH and 73+/
      11% chemical oxygen demand (COD) from the carwash wastewater with 25-200 mg L(-1)
      amended lubricant. The internal loop airlift reactor's simple operation and high
      stability demonstrate its high potential for use in treating lubricants in
      emulsified wastewater from carwashes and other industries.

PMID- 22398032
TI  - Simulation of HyperSPECT: a high-resolution small-animal system with in-line x
      ray optics.
AB  - SPECT has become an important tool in pre-clinical applications. Small-animal
      imaging systems based on the use of one or more pinhole collimators now reach sub
      half-mm resolution but unfortunately suffer from a compromise between sensitivity
      and resolution due to the pinhole collimators. We propose a small-animal SPECT
      system based not on pinholes but on in-line x-ray optics, which is rare in
      medical imaging systems for nuclear medicine. The x-ray lenses are optimized for
      27 keV for low-energy imaging with iodine-125. We believe that this new system,
      HyperSPECT, can simultaneously improve on sensitivity and resolution compared to
      today's state-of-the-art systems. A full three-dimensional simulation of the
      system has been performed including the prism-array lenses, pre- and post
      collimators and scintillator-based detector. Images of capillary phantoms have
      been reconstructed using an iterative image reconstruction method. Sensitivity
      was uniformly 0.37% throughout the 1 cm diameter spherical field of view and rod
      sizes of around 100 MUm diameter were distinguishable in the images of simulated
      capillary phantoms. These results indicate an increase in resolution by a factor
      of 5 during a simultaneous increase in sensitivity by a factor of 2 compared to
      the current state-of-the-art small-animal SPECT systems.

PMID- 22398033
TI  - Increase of HCV RNA concentration during hemodialysis treatment in patients with
      chronic hepatitis C.
AB  - BACKGROUND: In hemodialysis (HD) patients, a decrease of serum HCV RNA
      concentration during HD has been reported. OBJECTIVES: To evaluate the effect of
      two different extracorporeal blood treatments, HD and hemodiafiltration (HDF), on
      HCV RNA concentration under standardized conditions. STUDY DESIGN: Eleven chronic
      HD patients with chronic hepatitis C (CHC) and thirty-three non-uremic patients
      with CHC as controls were studied. Blood samples were collected at baseline (t=0
      min), 30 min (t=30), and 180 min (t=180) after start of HD or HDF. HCV RNA
      concentrations were determined by a real-time PCR assay. Values obtained 30 min
      and 180 min after start of HD or HDF were adjusted according to the
      ultrafiltration-induced hemoconcentration. RESULTS: Baseline HCV RNA
      concentrations were found to be similar in dialysis patients and controls
      (2.9E+06 vs. 5.8E+06 IU/ml). After adjustment for hemoconcentration, no
      significant differences of HCV RNA concentrations were observed when HD versus
      HDF treatments and blood samples collected pre versus those collected post
      membrane were compared. Adjusted HCV RNA concentrations increased by 13% (not
      significant) at 30 min and by 56% (p<0.001) at 180 min after start of HD or HDF.
      Inhibitory effects on PCR through heparin and uremic toxins could be excluded.
      CONCLUSIONS: In contrast to recent publications, a significant increase of serum
      HCV RNA within 180 min after start of HD or HDF was observed. Changes in serum
      HCV RNA concentration are independent from HD and HDF procedures, dialysis
      membrane, heparin concentration, and uremic toxins.

PMID- 22398034
TI  - Influenza in the immediate post-pandemic era: a comparison with seasonal and
      pandemic influenza in hospitalized patients.
AB  - BACKGROUND: Comparative data on severity and treatment of seasonal, pandemic and
      post-pandemic influenza virus infections are scarce. OBJECTIVES: To
      systematically analyze characteristics of hospitalized patients with influenza in
      the post-pandemic period compared to seasonal and pandemic influenza. STUDY
      DESIGN: Clinical and virological data of patients hospitalized in a tertiary
      referral hospital with post-pandemic influenza (2010-2011) were compared with
      those during seasonal influenza epidemics (2007-2009) and the influenza
      A(H1N1)pdm09 pandemic (2009-2010). RESULTS: 82 patients were admitted during the
      post-pandemic period, compared to 85 during the pandemic and 60 during seasonal
      influenza epidemics. No differences were observed in the occurrence of
      complicated illness and the need for intensive care. However, radiographic
      pneumonia was significantly more often diagnosed in patients with influenza
      A(H1N1)pdm09 compared to patients with seasonal influenza A (25% versus 71% in
      pandemic, p=0.004, and 55% in post-pandemic, p=0.047). Oseltamivir was more
      frequently prescribed in post-pandemic and pandemic patients compared to previous
      influenza seasons (48.9% resp. 76.5% versus 6.5%, p<0.0001). During the post
      pandemic period, patients with influenza B were significantly less often treated
      with oseltamivir compared to patients with influenza A (27.0% versus 48.9%,
      p=0.043), although the course of illness in patients with influenza B was
      comparable with influenza A. No upsurge of oseltamivir resistance was observed.
      CONCLUSIONS: In our center, severity of illness was comparable for all influenza
      seasons, although more radiographic pneumonia was diagnosed in patients with
      influenza A(H1N1)pdm09. Despite the increased use of oseltamivir, no increase in
      oseltamivir resistance was detected.

PMID- 22398035
TI  - Rare G3P[3] rotavirus strain detected in Brazil: possible human-canine
      interspecies transmission.
AB  - BACKGROUND: An unusual strain of human rotavirus G3P[3] (R2638 strain) was
      detected from a 1-year-old child patient during the epidemiological survey of
      rotavirus in the state of Sao Paulo, Brazil in 2011. OBJECTIVE: The aim of this
      study was to carry out sequence analyses of the two outer capsid proteins (VP4
      and VP7) of the R2638 strain detected in order to obtain further information of
      the genetic relationships between human and animal rotaviruses. STUDY DESIGN:
      Rotavirus G3P[3] was detected using a commercial immunoenzymatic assay, SDS-PAGE,
      and genotyped by RT-PCR. The analysis of the genetic relationship between human
      and animal rotaviruses was carried out by sequencing the VP7 and VP4 genes.
      RESULTS: The VP7 gene of the R2638 strain displayed the highest nucleotide
      identity to the canine strains A79-10 (96.6%) and CU-1 (96.2%) isolated in USA.
      The VP4 sequence showed the highest nucleotide identity to P[3] canine rotavirus
      strain RV52/96 isolated in Italy at 94.1%. Furthermore, the VP4 genes of P[3]
      strains could be discriminated into two phylogentically distinct clusters.
      CONCLUSION: The present study reinforces the hypothesis that animal's rotaviruses
      might be able to cross the species barriers, and the lack of systematic
      surveillance of rotavirus infection in small animals hinders the ability to
      establish firm epidemiologic connections. Moreover, in 2006 rotavirus vaccine was
      included in the Brazilian Immunization Program, and selective vaccine pressure
      could increase the circulation of uncommon strains. This is the first report of
      G3P[3] in over 20-year period of monitoring in Brazil.

PMID- 22398036
TI  - Emergence of cytomegalovirus resistance to foscarnet in a patient receiving
      foscarnet salvage therapy for multidrug-resistant HIV infection.
AB  - Foscarnet (FOS) is a pyrophosphate analogue that inhibits both cytomegalovirus
      (CMV) and human immunodeficiency virus (HIV) replication. We describe herein the
      emergence of CMV resistance to FOS in a 54-year-old man receiving FOS salvage
      therapy because of multidrug-resistant HIV-1 infection. Oral valganciclovir
      (VGCV) treatment allowed subsequently the improvement of FOS-resistant CMV
      infection.

PMID- 22398037
TI  - The rtL229 substitutions in the reverse transcriptase region of hepatitis B virus
      (HBV) polymerase are potentially associated with lamivudine resistance as a
      compensatory mutation.
AB  - BACKGROUND: It remains unclear whether hepatitis B virus (HBV) reverse
      transcriptase (RT) rtL229 substitutions influence HBV drug resistance. OBJECTIVE:
      The study was to investigate the association of HBV rtL229 substitutions with
      viral resistance to lamivudine (LAM). STUDY DESIGN: Entire HBV RT genes were
      amplified by nested PCR and sequenced from sera of 6000 nucleos(t)ide analog
      experienced patients with chronic HBV infection. The incidence and clinic
      relevance of rtL229 substitutions were analyzed. Replication-competent viral
      amplicons which harbored HBV genomes of wild-type, rtM204I, or rtM204I in
      conjunction with various rtL229 substitutions (rtL229F/W/M/V) were constructed.
      The amplicons were transfected into HepG2 cells for phenotyping of replication
      capacity and susceptibility to nucleos(t)ide analogs. RESULTS: The rtL229
      substitutions were detected in 6.57% (394/6000) of patients. Individual
      substitution incidences were 2.77%, 0.97%, 0.83% and 0.55% for rtL229V, rtL229F,
      rtL229M and rtL229W, respectively. The incidence of rtL229 substitutions was
      significantly higher in LAM-experienced patients (341/4220, 8.1%) than in LAM
      naive patients (53/1780, 3.0%), and were independently associated with genotypic
      LAM resistance (77.9% vs. 21.2%, OR 8.806, 95%CI 6.345-12.223) and low viral
      replication (HBV DNA <1000IU/mL) (4.60% vs. 24.2%, OR 0.478, 95%CI 0.254-0.898).
      Representative cases follow-up showed that rtL229F developed subsequent to
      rtM204I emergence during LAM treatment and regressed with rtM204I after LAM
      withdrawal. Functionally, rtL229F did not confer reduced susceptibility to LAM,
      but could restore replication capacity of rtM204I strain. CONCLUSION: The rtL229
      substitutions were potentially associated with LAM resistance in Chinese patients
      and rtL229F had characteristics of a compensatory mutation of rtM204I mutant.

PMID- 22398039
TI  - Familial collagenous colitis involving a 6-year old child.
AB  - Collagenous colitis is a recognised cause of persistent, non-bloody, watery
      diarrhoea. There are few cases of collagenous colitis reported in children or
      occurring within families. To our knowledge, no familial cases under 14 years of
      age have been reported previously; we describe a case of familial collagenous
      colitis affecting a 6-year old girl and her mother. The relevant published
      literature is reviewed and management is discussed. Colonic mucosal biopsies
      should be considered in both adults and children presenting with persistent
      watery diarrhoea even in the absence of any macroscopic abnormality at
      colonoscopy.

PMID- 22398038
TI  - Detection and quantification of influenza C virus in pediatric respiratory
      specimens by real-time PCR and comparison with infectious viral counts.
AB  - BACKGROUND: The epidemiological and clinical impacts of influenza C virus
      infection may have been underestimated by conventional viral culture screening
      alone. OBJECTIVE: To evaluate a newly developed real-time polymerase chain
      reaction (PCR) assay as a tool for diagnosing influenza C virus infection. STUDY
      DESIGN: The primers and probe for real-time PCR were designed to amplify the
      conserved region of the nucleoprotein gene based on the aligned sequences of nine
      isolates from 1967 to 2010. Respiratory specimens from children collected between
      January 2010 and August 2010 were examined for the presence of influenza C virus
      by cell culture and real-time PCR. Specimens that were positive for the virus
      using real-time PCR were further examined using an infectivity assay with
      embryonated hen's eggs. RESULTS: Of the 1203 specimens examined, 34 (2.8%) tested
      positive for the influenza C virus by cell culture and 51 (4.2%) tested positive
      by real-time PCR. The mean viral load and infectivity titer in specimens that
      tested positive using cell culture were 3.97*10(8)copies/ml and
      5.43*10(5)EID(50)/ml, respectively, and those in specimens that were negative
      using cell culture were 2.18*10(6)copies/ml and 3.67*10(2)EID(50)/ml,
      respectively. In the clinical specimens with viral loads less than
      10(5)copies/ml, it was not possible to isolate the virus using embryonated hen's
      eggs. The copy number-to-EID(50) ratio of the clinical specimens was much higher,
      ranging from 32 to 278,000, than those of culture fluid, ranging from 2.3 to
      13.5. CONCLUSION: The real-time PCR assay described here can be used as a
      sensitive method for diagnosing influenza C virus infection.

PMID- 22398040
TI  - The usefulness of factor XIII levels in Crohn's disease.
AB  - BACKGROUND AND AIMS: The assessment of inflammatory activity in Crohn's disease
      (CD) is challenging, and no specific laboratory marker is currently available.
      Several studies have reported decreased serum factor XIII levels in CD patients
      as a function of disease activity. We aimed to determine whether the factor XIII
      level could be a marker for the evolution of CD. METHODS: In this prospective,
      single-centre trial, 129 patients were included and categorised into two groups:
      functional bowel disorders (FBDs, n=42) and CD (n=86). The CD group was divided
      into two subgroups depending on disease activity, as defined by the Crohn's
      Disease Activity Index score: active disease (CDa, n=41) and disease remission
      (CDb, n=45). The factor XIII levels were evaluated for each patient. Serial
      factor XIII levels were evaluated in the patients within the CDa subgroup.
      RESULTS: The factor XIII levels were significantly different between the FBD
      (117.69%) and CD (101.89%) groups (p=0.009) but there was no significant
      difference between the CDa and CDb subgroups (99.04% vs 104.65%, p>0.05), and the
      levels did not vary during follow-up for the patients in the CDa subgroup. By
      multivariate analysis, factor XIII levels did not correlate with the time course
      of disease evolution, CRP, serum fibrin levels, platelet count, disease
      distribution within the bowel, or the presence of a fistulising form of CD.
      CONCLUSIONS: Our results confirm that factor XIII levels are decreased in CD
      patients but cannot be recommended as a marker for the disease activity.

PMID- 22398041
TI  - Genotyping should be considered the primary choice for pre-treatment evaluation
      of thiopurine methyltransferase function.
AB  - BACKGROUND AND AIMS: A pre-treatment determination of the thiopurine S
      methyltransferase (TPMT) genotype or phenotype can identify patients at risk of
      developing severe adverse reactions from thiopurine treatment. The risk of
      misclassifying a patient might be dependent on the method used. The aim of this
      study was to investigate the concordance between TPMT genotyping and phenotyping.
      METHODS: The data consist of 7195 unselected and consecutive TPMT genotype and
      phenotype determinations sent to the division of Clinical Pharmacology,
      Linkoping, Sweden. TPMT activity was measured in red blood cells (RBC) and the
      genotype determined by pyrosequencing for the three most common TPMT variants
      (TPMT *2, *3A, *3C). RESULTS: TPMT genotyping identified 89% as TPMT wild type
      (*1/*1), 10% as TPMT heterozygous and 0.5% as TMPT defective. The overall
      concordance between genotyping and phenotyping was 95%, while it was 96% among
      IBD patients (n=4024). Genotyping would have misclassified 8% of the TPMT
      defectives as heterozygous as compared to 11% if only TPMT activity had been
      measured. 11% of the heterozygous patients had a normal TPMT activity (>8.9 U/ml
      RBC) and 3% of the TPMT wild-type patients had an intermediate TPMT activity (2.5
      8.9 U/ml RBC). CONCLUSIONS: There is a risk for TPMT misclassification when only
      genotyping or phenotyping is used, but it is not reasonable to check both in all
      patients. Since TPMT genotyping is the more reliable test, especially in TPMT
      heterozygotes, we suggest that genotyping should be considered the primary choice
      for the pre-treatment evaluation of TPMT function before initiation of thiopurine
      therapy.

PMID- 22398042
TI  - Molecular alterations in colitis-associated colorectal neoplasia: study from a
      low prevalence area using magnifying chromo colonoscopy.
AB  - BACKGROUND AND AIM: Longstanding ulcerative colitis (UC) predisposes to
      colorectal cancer (CRC). To understand the molecular pathogenesis of colitis
      associated colorectal neoplasia (UC-CRN), we studied the frequency of
      microsatellite instability (MSI) and mutations in p53, BRAF and KRAS genes in the
      tissues of patients with long standing UC with or without neoplasia and compared
      them with colitis patients without risk of neoplasia, and those with sporadic
      colorectal neoplasia (S-CRN) in an area with lower prevalence for either disease.
      METHODS: Biopsies were obtained during magnifying chromo colonoscopy or routine
      colonoscopy in consecutive UC patients with high risk (UC-HR) and low risk (UC
      LR) of neoplasia, and those with S-CRN. MSI (NCI-Bethesda panel) and mutations in
      p53, KRAS and BRAF genes were analysed. RESULTS: Twenty-eight patients with UC
      HR, 30 with UC-LR and 30 with S-CRN were included. Six (21.4%) of UC-HR had
      neoplasia (Progressors). MSI was not detected in the UC-CRN group as compared to
      5 (16.7%) in the S-CRN group. p53 mutations occurred in 1 (3.3%) of UC-LR,
      increasing to 6 (27.3%, P<0.05) and 3 (50%, P<0.05) in the UC-HR subgroups
      without and with neoplasia respectively, as against 10 (33.3%) in sporadic
      neoplasia group. KRAS mutations were found only in the presence of neoplasia.
      None showed the BRAF mutation. CONCLUSIONS: In a population with a lower
      prevalence for UC and CRC, the molecular pathogenesis of colitis-associated
      colorectal neoplasia is comparable to that reported from areas with a higher
      prevalence of these diseases, MSI being an exception.

PMID- 22398043
TI  - A functional polymorphism in UGT1A1 related to hyperbilirubinemia is associated
      with a decreased risk for Crohn's disease.
AB  - BACKGROUND: An imbalance between the production of reactive oxygen species (ROS)
      and their capturing by antioxidants results in oxidative stress, this may play an
      important role in the pathogenesis of inflammatory bowel disease (IBD). Since
      bilirubin is an important endogenous antioxidant, increased levels of bilirubin
      may protect against IBD. UDP-glucuronosyltransferase 1A1 (UGT1A1) is the only
      enzyme involved in the conjugation of bilirubin and the common UGT1A1*28 allele
      in the UGT1A1 gene, which is strongly associated with Gilbert's syndrome in
      Caucasians, results in elevated plasma bilirubin levels. AIMS: To test the
      hypothesis that the UGT1A1*28 allele is associated with lower disease
      susceptibility to, and disease behavior within, IBD. In addition, a possible
      altered risk for developing IBD-drug related side-effects was explored.
      METHODOLOGY: Genomic DNA of 751 patients with IBD (209 patients with ulcerative
      colitis and 542 patients with Crohn's disease) and 930 healthy controls was
      genotyped for the UGT1A1*28 promoter polymorphism, and genotype distribution was
      compared between patients and controls. Genotype phenotype interactions were also
      investigated. RESULTS: Patients with Crohn's disease significantly less often
      bear the UGT1A1*28 homozygous genotype compared to the control group, with an
      odds ratio of 0.64, 95% CI: 0.42-0.98. The ulcerative colitis group showed no
      significant differences compared to controls. CONCLUSION: The homozygous state of
      the UGT1A1*28 polymorphism, associated with higher serum bilirubin levels, may be
      protective for the development of Crohn's disease, suggesting that the anti
      oxidant capacity of bilirubin may play a part.

PMID- 22398044
TI  - Internal fistula leakage due to a road traffic accident: a fortuitous diagnosis
      of Crohn's disease.
AB  - BACKGROUND AND AIM: Fistulae are one of the most frequent complications of
      Crohn's disease (CD) and occur in 30-40% of patients. Conversely, free
      perforation is a rare complication and is one of the indications for emergency
      surgery of CD because of secondary peritonitis. We report a case of a spontaneous
      fistula rupture secondary to a road traffic accident. METHODS: Case report.
      RESULTS: A 22 year-old man, with no personal significant medical history, was
      admitted in the emergency room after a road traffic accident. He underwent
      abdominal CT, which revealed pelvis fractures, abnormal bowel wall of the
      terminal ileum (wall thickening and mucosal enhancement), peritoneal effusion
      within the pelvis, mesenteric nodes and extra-luminal gas within an area of
      mesenteric inflammation: these features were suggestive of ileum perforation
      associated with inflammatory bowel disease, most likely CD. Laparoscopic
      assessment was decided and an ileocaecal resection with ileocolonic anastomosis
      was performed. Histological analysis revealed terminal ileitis with ulcers, non
      caseating granulomas and submucosal fibrosis, a transparietal fistula and a
      caecoappendicular inflammation, confirming CD. Post surgical outcome was
      uneventful and the patient was discharged at day 9. CONCLUSION: Our patient
      presented this rare complication revealing CD. The involvement of the terminal
      ileum and fistulae were characteristics of CD. Rupture of the fistula was favored
      by the trauma and responsible for the peritonitis. A resection with primary
      anastomosis was possible. To our knowledge, it is the first case described for
      the rupture of an ileal fistula secondary to traumatism in a patient with CD.

PMID- 22398045
TI  - Thiopurine treatment in inflammatory bowel disease: response predictors, safety,
      and withdrawal in follow-up.
AB  - BACKGROUND AND AIMS: Thiopurines represent the mainstay of immunosuppressive
      therapy in inflammatory bowel diseases. Since it is likely that response to
      therapy and adverse events depends on the genetic background of patients our
      study aimed to evaluate retrospectively response to therapy and safety in a mixed
      IBD population in Southern Europe. METHODS: We evaluated demographic and clinical
      data of our patients treated with thiopurines. after 6 months in responders and
      non-responders to therapy. Moreover the likelihood to remain in thiopurine
      monotherapy was evaluated in responders, whereas adverse events were investigated
      in all patients. RESULTS: Among disease- and patient-related parameters a shorter
      disease duration, female gender and ileal disease in Crohn's patients were
      associated with better response. By ROC analysis, the best predictors of response
      were decreasing values of C-reactive protein and erythrocyte sedimentation rate.
      In the long-term more than half of IBD patients who responded at 6 months
      remained on monotherapy at 42 months. Flu-like syndrome represented the most
      frequent adverse event followed by abnormalities of liver function tests and
      myelotoxicity. Adverse events did occur at any time and were frequently
      impredictable. CONCLUSIONS: In this retrospective study, thiopurines showed a
      good clinical efficacy, especially in patients with short duration of disease.
      Normalization of markers of systemic inflammation represents the most useful tool
      to assess response. Careful monitoring of patients is required during the whole
      duration of treatment although it may not prevent all severe complications.

PMID- 22398046
TI  - Personality and fatigue perception in a sample of IBD outpatients in remission: a
      preliminary study.
AB  - BACKGROUND AND AIMS: Fatigue is considered as a feature of IBD. Nevertheless,
      medical variables would partly explain this complex phenomenon. Psychological
      variables would be especially connected to fatigue for patients in remission.
      Moreover, personality is known to be linked to the fatigue of patients with CFS.
      This preliminary study aimed to determine if personality dimensions are linked to
      the perception of fatigue in IBD. METHODS: 81 IBD outpatients in remission
      completed the MFI (fatigue); ISI, EES (sleep disturbances); TCI-R (personality);
      HADS (depression and anxiety). Medical data were collected (ferritin, C-reactive
      protein, number of flare-ups, number of hospitalizations, duration of the disease
      and surgical sequelae). RESULTS: With the exception of surgical sequelae, none of
      the medical variables was linked to fatigue perception. Anxiety and sleep
      disturbances were the most continuously connected to fatigue perception.
      Significant relationships were observed between personality categorization on
      Persistence, Self-Directness and the level of fatigue. CONCLUSION: In order to
      improve vitality in IBD patients in remission, identification and treatment of
      psychological aspects should become a dimension of disease management. Fatigue
      should not be considered only as a direct feature of IBD.

PMID- 22398047
TI  - Fistulizing pattern in Crohn's disease and pancolitis in ulcerative colitis are
      independent risk factors for cancer: a single-center cohort study.
AB  - BACKGROUND & AIMS: The combined role of immunomodulators (IMM) and clinical
      characteristics of Inflammatory Bowel Disease (IBD) in determining the cancer
      risk is undefined. The aim was to assess whether clinical characteristics of IBD
      are independent risk factors for cancer, when considering thiopurines and anti
      TNFs use. METHODS: In a single-center cohort study, clinical characteristics of
      IBD patients with IBD duration >=1 year and >=2 visits from 2000 to 2009 were
      considered. Tests for crude rates and survival analysis methods were used to
      assess differences of incidence of cancer between groups. The methods were
      adjusted for the time interval between diagnosis and immunomodulatory treatments.
      RESULTS: IBD population included 1222 patients :615 Crohn's disease (CD), 607
      ulcerative colitis (UC). Cancer was diagnosed in 51 patients (34 CD,17 UC), with
      an incidence rate of 4.3/1000 pt/year. The incidence rate of cancer was
      comparable between CD and UC (4.6/1000 pt/year vs 2.9/1000 pt/year ;p=n.s.).
      Cancer most frequently involved the breast, the GI tract, the skin. Lymphoma was
      diagnosed in CD (1HL, 1NHL,0 HSTCL). Risk factors for cancer included older age
      at diagnosis of IBD (CD: HR 1.25;95%CI 1.08-1.45; UC:HR 1.33;95%CI 1.15-1.55 for
      an increase by 5 years; p=0.0023; p=0.0002), fistulizing pattern in CD (HR 2.55;
      95%CI 1.11-5.86,p=0.0275), pancolitis in UC (HR 2.79;95%CI 1.05-7.40 p=0.0396 vs
      distal). IMM and anti-TNFs did not increase the cancer risk in CD, neither IMM in
      UC (anti-TNFs risk in UC not feasible as no cases observed). CONCLUSIONS:
      Fistulizing pattern in CD, pancolitis in UC and older age at diagnosis of IBD are
      independent risk factors for cancer.

PMID- 22398048
TI  - Neuroimmune interactions in patients with inflammatory bowel diseases: disease
      activity and clinical behavior based on Substance P serum levels.
AB  - BACKGROUND AND AIM: The neuropeptide Substance P, plays a key role in modulating
      neuroimmune interactions in patients with inflammatory bowel diseases. We
      analyzed Substance P serum levels in patients with ulcerative colitis and Crohn's
      disease, to detail the involvement of the neuropeptide in the pathophysiology of
      these disorders. METHODS: Serum samples were collected from 61 patients with
      ulcerative colitis (24 with active and 37 with inactive disease), 66 patients
      with Crohn's disease (29 with active and 37 with inactive disease) and 45 healthy
      subjects, enrolled into the study. Neuropetide serum levels were measured by
      means of an ELISA/EIA. Associations with disease activity and patients clinical
      features were also taken into account. RESULTS: Compared to controls, Substance P
      serum levels were significantly increased in both patients with ulcerative
      colitis and Crohn's disease, (p<0.001). In patients with ulcerative colitis,
      levels paralleled disease activity (p=0.014), and the amount of the neuropeptide
      was considerably decreased during clinical and endoscopic remission of the
      disease, (p=0.025). Conversely, median Substance P levels did not differ between
      patients with active and inactive Crohn's disease. However, levels of the
      neuropeptide were more often elevated in patients with inactive and
      stricturing/fistulizing Crohn's disease, (p=0.002). CONCLUSIONS: Data underline
      that Substance P might exerts important immunomodulatory functions in
      inflammatory bowel disease. This study suggests a potential role for Substance P
      serum levels in monitoring intestinal inflammation in patients with inflammatory
      bowel disease.

PMID- 22398049
TI  - Identification of areas of functioning and disability addressed in inflammatory
      bowel disease-specific patient reported outcome measures.
AB  - BACKGROUND AND AIMS: Patient-reported outcome measures (PROMs) make it possible
      to assess health-status problems from the perspective of persons suffering from a
      disease. The objective of the paper is to examine and compare the contents of
      PROMs related to IBD based on the World Health Organization's International
      Classification of Functioning, Disability and Health (ICF) as the frame of
      reference. METHODS: A systematic literature review (1999-2009) in the databases
      Medline, EMBASE, PsycINFO, CINAHL and CENTRAL was performed to select IBD
      specific PROMs. Abstracts and full-text articles were checked applying predefined
      eligibility criteria; IBD-specific PROMs were identified. The contents of the
      identified PROMs were examined by linking the items to ICF categories. The linked
      ICF categories of the PROMs were then compared. RESULTS: The review resulted in
      the selection of eight IBD-specific PROMs (e.g., Cleveland Global Quality of
      Life, Inflammatory Bowel Disease Quality of Life Questionnaire, Inflammatory
      Bowel Disease Questionnaire-32, Rating Form of IBD Patient Concerns, Short
      Inflammatory Bowel Disease Questionnaire). In total, 129 items were identified,
      the majority of which (n=90; 69.8%) could be linked to specific ICF categories.
      None of the linked categories were contained in all PROMs. The most frequently
      identified categories were 'b1300 Energy level', 'b5254 Flatulence', 'd910
      Community life' and 'd920 Recreation and leisure'. CONCLUSION: The present study
      provides an overview of IBD-specific PROMs and their items. The results of the
      content comparison provide valuable information to facilitate and account for the
      selection of appropriate PROMs for different purposes of data collection in
      clinical and research settings.

PMID- 22398050
TI  - Fast and sharp decrease in calprotectin predicts remission by infliximab in anti
      TNF naive patients with ulcerative colitis.
AB  - AIM: To evaluate the effect of infliximab induction therapy on calprotectin
      levels in patients with ulcerative colitis (UC). PATIENTS AND METHODS: In this
      prospective study 53 patients with active UC from 17 centers were treated with
      infliximab therapy (5 mg/kg) at baseline, week 2, and week 6. Faecal calprotectin
      was measured every week. Sigmoidoscopies were performed at baseline, week 6 and
      week 10. RESULTS: Median calprotectin levels decreased from 1260 (IQR 278.5-
      3418) at baseline to 72.5 (IQR 18.5 - 463) at week 10 (p<0.001). After 10 weeks,
      infliximab therapy induced endoscopic remission and a decrease in calprotectin
      to<50 mg/kg or at least a 80% decrease from baseline level in 58% of patients. A
      significant and steep decrease of calprotectin levels was seen at week 2 for
      patients with an endoscopic remission at week 10 as compared to patients who did
      not show a remission. (p<0.001). At week 10 an excellent correlation was found
      between endoscopic remission and clinical Mayo score reflected by an AUC of ROC
      analyses of 0.94 (0.87-1) and with calprotectin measurements (AUC 0.91 (0.81-1))
      : all patients with calprotectin levels <50 mg/kg, and a normal clinical Mayo
      score (=0) were in endoscopic remission. CONCLUSIONS: Infliximab induces a fast
      and significant decrease of faecal calprotectin levels in anti-TNF naive patients
      with ulcerative colitis predictive for remission of disease.

PMID- 22398051
TI  - Adalimumab reversed a severe lymphopenia in a patient with Crohn's disease.
AB  - Patients with Crohn's disease are frequently found to have low peripheral
      lymphocyte counts. Lymphopenia has been linked to disease activity, the effects
      of therapy and the presence of an abnormal T regulatory (T(reg)) function. We
      present a patient with Crohn's disease and a severe total and CD4 lymphopenia
      that did not resolve after discontinuation of immunosuppressive treatment and
      resective surgery. Complete clinical remission and persistent normal levels of
      total and CD4 lymphocytes were observed after starting therapy with the anti
      tumor necrosis factor monoclonal antibody adalimumab.

PMID- 22398052
TI  - Management of inflammatory bowel disease with vitamin D: beyond bone health.
AB  - A relationship between vitamin D and several disorders, including Crohn's disease
      (CD), has recently been proposed. Vitamin D appears to have several important
      actions beyond the maintenance of bone health, including various effects on the
      immune system. Vitamin D deficiency has been implicated in the development of CD,
      and its analogues may have a role in the treatment of CD. Current research also
      suggests a role for vitamin D in counteracting some IBD-specific complications,
      including osteopenia, colorectal neoplasia, and depression. There remains a need
      for prospective studies to further delineate these relationships. Given current
      evidence and the apparent safety of vitamin D supplementation, it appears
      reasonable to screen for and treat vitamin D deficiency in patients with IBD.

PMID- 22398053
TI  - Use of small bowel MRI enteroclysis in the management of paediatric IBD.
AB  - INTRODUCTION: Children with inflammatory bowel disease (IBD) frequently present
      with small bowel involvement at some stage of their disease. Hence, reliable
      assessment of the entire small bowel is required in order to adjust treatment
      accordingly. Recently, magnetic resonance imaging (MRI) of the small bowel in
      combination with luminal contrast agent delivered via a naso-jejunal tube (MR
      enteroclysis) is an emerging technique demonstrating good results in adult
      patients. However, data on its use and benefits in children is limited. AIMS: In
      this study we report our experience on performing small bowel MR enteroclysis
      (MRE) in children with IBD. Specifically, we reviewed indications, MR findings,
      advantages and disadvantages of the technique in a tertiary unit. METHODS: A
      total of 34 MRE studies (29 paediatric IBD patients) were retrospectively
      analysed. All patients underwent upper and lower endoscopy under general
      anaesthetic (GA) the day before MR imaging was performed. Nasojejunal (NJ)-tube
      was placed during endoscopy. RESULTS: Frequently detected findings included small
      and large bowel wall thickening, small bowel strictures and intestinal lymph node
      enlargement. Importantly, in all our clinical cases, MRE results were key to
      making a clinical decision in the given scenario regardless of whether MRE
      findings were positive or negative. CONCLUSIONS: Within our setup, MR
      enteroclysis is a well-tolerated, sensitive technique for small bowel imaging,
      providing detailed information at crucial clinical decision points. Moreover,
      accurate information then allows appropriate clinical decisions to be made.

PMID- 22398054
TI  - Clinical and radiographic presentation of superior mesenteric vein thrombosis in
      Crohn's disease: a single center experience.
AB  - BACKGROUND: Mesenteric vein thrombosis (MVT) is a rare and frequently
      underdiagnosed complication of Crohn's disease (CD). This study describes the
      clinical and radiological characteristics of CD /patients with superior
      mesenteric vein thrombosis (MVT) diagnosed by CT/MRI. PATIENTS AND METHODS: The
      database of Crohn's disease patients treated in Sheba Medical Center between 2005
      2010 was searched for MVT diagnosis. Imaging studies of identified patients were
      retrieved and reviewed by an experienced abdominal radiologist. MVT was defined
      by superior mesenteric vein obliteration and/or thrombus in the vessel lumen on
      abdominal imaging. The clinical and radiologic data of these patients were
      collected from the medical records. RESULTS: MVT was demonstrated in 6/460 CD
      patients. Five patients had stricturing disease, and one patient had a combined
      fistulizing and stricturing disease phenotype. All patients had small bowel
      disease, but 3/6 also had colonic involvement. No patient had a prior
      thromboembolic history or demonstrable hypercoagulability. One patient had an
      acute SMV thrombus demonstrable on CT scanning, the remaining patients showed an
      obliteration of superior mesenteric vein. Two patients received anticoagulation
      upon diagnosis of thrombosis. No subsequent thromboembolic events were recorded.
      CONCLUSIONS: The incidence of mesenteric vein thrombosis is likely to be
      underestimated in patients with Crohn's disease. Both CT and MRI imaging
      demonstrate the extent of enteric disease and coincident SMV thrombosis. In our
      cohort, thrombosis was associated with stricturing disease of the small bowel.
      The clinical impact of SMV thrombosis and whether anticoagulation is mandatory
      for all of these patients remains to be determined.

PMID- 22398055
TI  - Pneumocystosis in a patient with Crohn's disease treated with combination therapy
      with adalimumab.
AB  - Pneumocystis jirovecii pneumonia (PCP) is a potential complication of
      immunosuppression. Crohn's disease (CD) is an immune granulomatous disorder
      characterized by transmural inflammation that can affect any part of the
      gastrointestinal tract. Its treatment is based on steroids and immunosuppressants
      but in non-responders, biologic compounds such as anti-tumor necrosis factor
      alpha (TNF) antibodies have been used. Neutralization of TNF causes a decrease in
      the inflammatory response but increases susceptibility to opportunistic
      infections such as fungal infections. We report a young male with chronic
      diarrhea, fever and weight loss who was diagnosed with CD and began conventional
      treatment with immunosuppressants, but due to lack of response after several
      weeks, biologic therapy with adalimumab was initiated. Seven weeks later he
      developed persistent fever and upper respiratory symptoms. After chest CT,
      bronchoscopy and bronchial lavage, P. jirovecii was identified by silver staining
      and confirmed by immunofluorescence. To our knowledge this is the second case of
      pneumocystosis associated with the use of adalimumab in CD and the first reported
      Mexican case confirmed by microbiological and immunological studies in this
      setting.

PMID- 22398056
TI  - Impact of budesonide on liver function tests and gut inflammation in patients
      with primary sclerosing cholangitis and ileal pouch anal anastomosis.
AB  - BACKGROUND AND AIM: Budesonide has been studied in patients with primary
      sclerosing cholangitis (PSC). This study was designed to evaluate the efficacy of
      oral budesonide on liver function tests in patients with PSC and pouchitis
      associated with ileal pouch-anal anastomosis (IPAA). MATERIALS AND METHODS: The
      study group consisted of 18 pouch patients with underlying ulcerative colitis
      (UC) and PSC who were treated with 9 mg daily of budesonide for their underlying
      pre-pouch ileitis and pouchitis for 1-3 months followed by 3-6 mg maintenance for
      another 9 months. Demographic and clinical variables were analyzed. RESULTS: The
      mean age was 39.4+/-12.4 years (range, 21-59 years). There was no significant
      change in aspartate aminotransferase (AST) [median (interquartile range) (IQR) 32
      (25, 43.8) vs. 35.5 (25.5, 53), p=0.35], alanine aminotransferase (ALT) [37.5
      (25.5, 49.5) vs. 40 (30, 84.3), p=0.29], alkaline phosphatase [142.5 (98.5,
      264.5) vs. 126 (94.3, 189.5), p=0.35], serum bilirubin [0.7 (0.4, 1.3) vs., 0.6
      (0.4, 1.6), p=0.13] or albumin levels [4.3 (3.9, 4.4) vs. 4.2 (3.8, 4.4), p=0.22]
      at the end of the treatment period (1 year). The revised Mayo Risk Score did not
      change significantly and three patients required evaluation for liver
      transplantation during treatment. There was a significant improvement in the
      endoscopy subscores in the afferent limb and pouch after a year of budesonide
      treatment (p=0.001). CONCLUSIONS: Oral budesonide appears to have no impact on
      liver function tests in pouch patients with PSC. However it significantly
      improved afferent limb and pouch inflammation in IPAA patients.

PMID- 22398057
TI  - Profiles of circulating cytokines in patients with Crohn's disease under
      maintenance therapy with infliximab.
AB  - BACKGROUND AND AIMS: The effects of maintenance infliximab for Crohn's disease
      vary widely among patients. The aim of this study was to examine the cytokine
      profiles and to identify possible markers predictive of therapeutic effect of
      maintenance infliximab. METHODS: Cytokine profiles of 35 Crohn's disease patients
      under maintenance infliximab therapy were analyzed prospectively. Blood samples
      were obtained prior to, and 2 and 6 weeks after infliximab infusion. Circulating
      cytokine values of interleukin (IL)-23, IL-17A, IL-12, IL-6, interferon gamma
      (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) were compared according
      to the disease activity and therapeutic efficacy. Patients were classified into
      either the active or quiescent phase according to their disease activity at
      baseline. Patients were also divided into a sustained response group and non
      sustained response group according to therapeutic efficacy of infliximab
      determined 2 and 6 weeks after infliximab infusion. RESULTS: At baseline, serum
      levels of IL-23 (p<0.05), IL-17A (p<0.01), IFN-gamma (p<0.05), and IL-6 (p<0.01)
      were significantly higher in active Crohn's disease than in quiescent disease.
      These cytokine levels remained unchanged during the follow-up period. When serum
      cytokine levels were compared between groups classified by therapeutic efficacy
      of infliximab, patients in the non-sustained response group had a significantly
      higher level of serum IL-17A than those in the sustained response group (p<0.05).
      There were also trends toward higher serum IL-23 and IL-12 in the former than in
      the latter. CONCLUSION: Higher levels of IL-17A, IL-23, and IL-12 at baseline may
      be predictive markers for poor therapeutic response to maintenance infliximab
      therapy.

PMID- 22398058
TI  - Mortality in ulcerative colitis and Crohn's disease. A population-based study in
      Finland.
AB  - BACKGROUND: An increased mortality has been reported in patients with Crohn's
      disease (CD), while figures have remained similar or decreased in patients with
      ulcerative colitis (UC) compared to the population in general. We evaluated the
      long-term mortality risk of patients with inflammatory bowel diseases (IBD) in a
      well-defined population. METHODS: The data were based on a prospective IBD
      register in our catchment area; follow-up covered 1986-2007. The population based
      cohort comprised 1915 adult patients, 1254 with UC, 550 with CD, and 111 with
      inflammatory bowel disease unclassified (IBDU). The mortality rate and causes of
      death were obtained from Statistics Finland. RESULTS: We recorded 223 deaths
      among the 1915 patients with IBD within a follow-up of 29,644 person-years. The
      standardised mortality rate (SMR) was 1.14 in CD and 0.90 in UC. In cause
      specific mortality; the risk of death in diseases of the digestive system was
      significantly increased in CD (SMR 5.38). The mortality in colorectal cancer was
      non-significantly increased in both UC and CD (SMR 1.80 and 1.88, respectively).
      Compared to the background population, there were significantly fewer deaths due
      to mental and behavioural disorders due to use of alcohol (0 observed, 10.2
      expected in IBD). CONCLUSIONS: The overall mortality in CD and CU was not
      different from that in the population. In cause-specific mortality, diseases of
      the digestive system were significantly increased. Deaths due to mental and
      behavioural disorders resulting from alcohol consumption were less common in
      patients with IBD than in the population at large in Finland.

PMID- 22398059
TI  - Induction of psoriasis with anti-TNF agents in patients with inflammatory bowel
      disease: a report of 21 cases.
AB  - AIM: Anti-tumor necrosis factor (TNF)-alpha agents are widely used for the
      treatment of both inflammatory bowel disease (IBD) and psoriasis. Psoriatic skin
      lesions induced by anti-TNF have been described in patients with IBD. We report a
      case series of psoriasis induced by anti-TNF agents in IBD patients. METHODS:
      Systematic analysis of cases of psoriasis induced by anti-TNF in an IBD patient
      cohort in tertiary hospitals of Madrid. RESULTS: A total of 21 of 1294 patients
      with IBD treated with anti-TNF-alpha agents developed drug-induced psoriasis
      (cumulative incidence 1.62%; 95% CI 1.06%-2.47%): 14 patients with infliximab and
      7 with adalimumab; seventeen with Crohn's disease, 4 with ulcerative colitis. The
      onset of skin lesions varied in a wide range of time (after a mean 13+/-8 doses).
      The most frequent site of skin lesions was the limbs (62%) followed by the trunk
      (48%) and the scalp (43%). The psoriasis phenotypes were plaque psoriasis (57%),
      scalp (14%), palmoplantar pustulosis (14%), pustular generalized psoriasis (5%),
      guttate (5%) and inverse (5%). Four patients interrupted the anti-TNF treatment,
      and that led to the complete regression of lesions in 1 of them. The other 17
      patients were maintained on anti-TNF therapy and managed with topical steroids.
      CONCLUSION: Psoriatic lesions can be induced by anti-TNF drugs. Plaque psoriasis
      on the extremities and trunk were the most frequent presentations in our series.
      Topical steroid treatment is effective in most patients. Anti-TNF discontinuance
      may be reserved for patients with severe psoriasis or patients without response
      to topical therapy.

PMID- 22398060
TI  - Mesalazine in left-sided ulcerative colitis: efficacy analyses from the PODIUM
      trial on maintenance of remission and mucosal healing.
AB  - BACKGROUND AND AIM: Left-sided colitis is the most prevalent subtype of
      ulcerative colitis, a chronic inflammatory disease of the colon. The standard of
      care for mild-to-moderate ulcerative colitis is mesalazine. The PODIUM study
      compared a once daily to a twice daily dosing regimen of a slow-release
      mesalazine (Pentasa(r)); here we assess the efficacy, in terms of maintenance of
      remission and mucosal healing, of both regimens in patients with left-sided
      disease. PATIENTS AND METHODS: Eligible patients were randomised to once daily
      (1*2 g) or twice daily (2*1 g) oral treatment with mesalazine, for 12 months.
      Disease activity was assessed clinically and endoscopically at baseline and at 12
      months using the Ulcerative Colitis Disease Activity Index, without endoscopic
      assessment at months 4 and 8. RESULTS: The study met the primary endpoint of non
      inferiority in terms of remission, for once daily versus twice daily dosing, in
      patients with left-sided ulcerative colitis; an 8% difference was reported in the
      12-month clinical and endoscopic remission rates (69% [95% CI: 59.5-76.5] and 61%
      [95% CI: 51.4-69.6] with once daily and twice daily dosing, respectively;
      p=0.310). Mucosal healing scores after 12 months were 0 or 1 for 84.4% of the
      once daily and 78.8% of the twice daily population. Slow-release mesalazine was
      well tolerated in both dosing regimens, with no difference in reported adverse
      events. CONCLUSIONS: Once daily slow-release mesalazine is similarly effective to
      the standard twice daily schedule in patients with left-sided ulcerative colitis
      for the maintenance of remission in mild-to-moderate disease.

PMID- 22398061
TI  - Severe disease on endoscopy and steroid use increase the risk for bowel
      perforation during colonoscopy in inflammatory bowel disease patients.
AB  - BACKGROUND AND AIM: Colonoscopic perforation is a rare complication. We sought to
      determine its risk factors in patients with inflammatory bowel disease (IBD).
      MATERIALS AND METHODS: The study group consisted of 19 IBD patients who had
      perforation secondary to diagnostic or therapeutic colonoscopy from January 2002
      to October 2010. The control group consists of 76 IBD patients undergoing
      colonoscopy and no perforations that were matched based on indication in a 4:1
      ratio to the study group. Demographic and clinical variables as well as
      perforation outcomes were analyzed by univariate and multivariate analyses.
      RESULTS: There were a total of 5295 colonoscopies done during the study period in
      IBD patients of which 19 patients had perforation. The prevalence of perforation
      in IBD patients was 0.3%. Of the 19 patients, 12 had Crohn's disease (CD) and 7
      had ulcerative colitis (UC). Patients in the perforation group were more likely
      treated with steroids (68.4% vs. 21.1%, p<0.001) and had severe disease on
      endoscopy (31.6% vs. 10.1%, p=0.03) than that in the control groups. On
      multivariate analysis, severe disease on endoscopy (adjusted odds ratio
      [aOR]=3.82, 95% confidence interval [CI]=1.03-15.24) and steroid treatment
      (aOR=7.68; 95% CI=1.48, 39.81) were independently associated with the risk of
      perforation. The median length of stay in the perforation group was 10 days
      (range 2-23 days). There was no mortality in our study. CONCLUSIONS: There
      appears to be a higher risk of colonoscopy-associated perforation in IBD patients
      with active disease and on steroids.

PMID- 22398062
TI  - Anti-TNF-alpha antibodies improve intestinal barrier function in Crohn's disease.
AB  - BACKGROUND AND AIMS: Intestinal barrier function in Crohn's disease patients and
      their first degree healthy relatives is impaired. The increased intestinal
      permeability may result in an enhanced mucosal immune response and thereby
      aggravate intestinal inflammation. Humanised anti-TNF-alpha antibodies have been
      shown to be effective in the treatment of active Crohn's disease and in the
      treatment of entero-cutaneous fistula. The aim of the present study was to
      investigate the influence of anti-TNF-alpha antibody (infliximab) treatment on
      the intestinal barrier function of patients with active Crohn's disease. METHODS:
      The differential intestinal uptake of lactulose and mannitol was measured to
      quantify intestinal permeability in patients with long standing active Crohn's
      disease (n=17) directly before and seven days after treatment with infliximab (5
      mg/kg bodyweight). In parallel, intestinal permeability was studied in a healthy
      control group (n=20). Serum samples were analysed with pulsed amperometric
      detection after separation on an anion exchange column. RESULTS: Intestinal
      permeability was significantly increased in all patients with Crohn's disease
      (L/M ratio 0.24+/-0.17) prior to infliximab treatment compared to the control
      group (L/M ratio 0.01+/-0.02; p-value <1*10(-7)). Treatment of patients with
      infliximab resulted in a marked decrease of intestinal permeability as measured
      by L/M ratio from 0.24+/-0.17 before to 0.02+/-0.02 (p-value <1*10(-7)) seven
      days after infliximab application. CONCLUSIONS: Treatment with anti-TNF-alpha
      antibodies improved impaired intestinal barrier function in patients with Crohn's
      disease. This effect may correlate to the well documented anti-inflammatory
      effect of TNF-alpha blockade in this intestinal disease.

PMID- 22398063
TI  - Herpes simplex virus-1 infection of colonic explants as a model of viral-induced
      activation of Crohn's disease.
AB  - The exogenous triggers responsible for Crohn's disease (CD) relapses are not
      often identified. Cytomegalovirus and other members of the herpesvirus family
      have been implicated in precipitating relapses. However, the role of viral
      infections in the immunopathogenesis of CD remains poorly understood. We describe
      an ex-vivo model of primary viral infection of CD tissue with Herpes Simplex
      Virus type I (HSV-1). IL-6 and CD68 served as markers for CD inflammation, type I
      IFNs for viral infection. Colonic explants obtained from CD resections were
      infected via the luminal or the submucosal compartments with HSV-1 or mock virus
      solution, at varying concentrations for up to 20 h. Serial tissue sections were
      assayed for expression of HSV-1 specific antigens, CD-68, IL-6 and DC-SIGN.
      Culture supernatants were tested for IL-6 and type I IFN production. Positive
      immunostaining for HSV-1 specific antigens was consistently detectable using
      11*10(6)PFU from 13 h onwards, mainly on cells located in the submucosa, and in
      the perivascular area. CD68 was up-regulated in lamina propria macrophages from
      mildly and non-inflamed CD tissue after HSV-1 infection. IL-6+ cells in the
      infected tissues were mainly submucosal DC-SIGN+ dendritic cells. IL-6 and IFN
      beta levels were higher in the supernatants from HSV-1-infected explants compared
      to controls after 20 h of culture (p<0.01). These data show increased expression
      of inflammatory markers during the initial stages of HSV-1 primary infection
      using CD colonic explants. This in vitro model appears promising to study the
      immunoregulatory changes induced by microbial infection in reactivation of CD.

PMID- 22398064
TI  - Patients with Crohn's disease experience reduced general health and vitality in
      the chronic stage: ten-year results from the IBSEN study.
AB  - BACKGROUND AND AIMS: Data on the long-term effects of Crohn's disease (CD) on
      health-related quality of life (HRQoL) is scarce. We aimed to determine the HRQoL
      in CD patients 10 years after disease onset, to compare the results to the
      general population and to identify variables that could affect HRQoL. METHODS: CD
      patients from a population-based inception cohort (the IBSEN Study) met at a
      prescheduled ten-year follow-up. In addition to a structured interview, review of
      hospital records, clinical examination, laboratory tests and ileocolonoscopy,
      they completed a patient-reported questionnaire including the Short Form 36 (SF
      36) and the Norwegian Inflammatory Bowel Disease Questionnaire (N-IBDQ). The SF
      36 scores were compared to scores from the general population using one-sample t
      tests. Standardized scores were calculated and interpreted according to Cohen's
      effect size index. The associations between relevant clinical and demographic
      factors and HRQoL were examined through linear regression analyses. RESULTS:
      Ninety-nine patients completed the HRQoL questionnaires (response rate 86%).
      Median age 39 years, 42% women. Compared to the general population the patients
      reported significantly lower SF-36 scores on the general health and vitality
      dimensions. IBDQ total scores were in line with scores of patients in remission.
      Except for current symptom severity no clinical parameters affected HRQoL scores.
      Work status and sick leave affected HRQoL negatively. CONCLUSIONS: In this
      chronic stage of CD, reduced general health and vitality scores need attention
      while reductions in disease specific HRQoL seem to be less predominant.

PMID- 22398065
TI  - Disease severity does not affect the interval between IBD diagnosis and the
      development of CRC: results from two large, Dutch case series.
AB  - BACKGROUND: The increased risk of colorectal cancer (CRC) in patients with
      inflammatory bowel disease (IBD) is well established. The incidence of IBD
      related CRC however, differs markedly between cohorts from referral centers and
      population-based studies. In the present study we aimed to identify
      characteristics potentially explaining these differences in two cohorts of
      patients with IBD-related CRC. METHODS: PALGA, a nationwide pathology network and
      registry in The Netherlands, was used to search for patients with IBD-associated
      CRC between 1990 and 2006. Patients from 7 referral hospitals and 78 general
      hospitals were included. Demographic and disease specific parameters were
      collected retrospectively using patient charts. RESULTS: A total of 281 patients
      with IBD-associated CRC were identified. Patients from referral hospitals had a
      lower median age at IBD diagnosis (26 years vs. 28 years (p=0.02)), while having
      more IBD-relapses before CRC diagnosis than patients from general hospitals (3.8
      vs. 1.5 (p<0.01)). In patients from referral hospitals, CRC was diagnosed at a
      younger age (47 years vs. 51 years (p=0.01)). However, the median interval
      between IBD diagnosis and diagnosis of CRC was similar in both cohorts (19 years
      in referral hospitals vs. 17 years in general hospitals (p=0.13)). CONCLUSIONS:
      IBD patients diagnosed with CRC treated in referral hospitals in The Netherlands
      are younger at both the diagnosis of IBD and CRC than IBD patients with CRC
      treated in general hospitals. Although patients from referral centers appeared to
      have a more severe course of IBD, the interval between IBD and CRC diagnosis was
      similar.

PMID- 22398066
TI  - Olfactomedin-4 is a glycoprotein secreted into mucus in active IBD.
AB  - BACKGROUND: Olfactomedin-4 (OLFM4) is a glycoprotein characteristic of intestinal
      stem cells and apparently involved in mucosal defense of the stomach and colon.
      Here we studied its expression, regulation and function in IBD. METHODS: The
      expression of OLFM4, mucins Muc1 and Muc2, the goblet cell differentiation factor
      Hath1 and the proinflammatory cytokine IL-8 was measured in inflamed or
      noninflamed colon in IBD patients and controls. OLFM4 protein was located by
      immunohistochemistry, quantified by Dot Blot and its binding capacity to
      defensins HBD1-3 was investigated. The influence of bacteria with or without the
      Notch blocker dibenzazepine (DBZ) and of several cytokines on OLFM4 expression
      was determined in LS174T cells. RESULTS: OLFM4 mRNA and protein were
      significantly upregulated in inflamed CD (4.3 and 1.7-fold) and even more
      pronounced in UC (24.8 and 3.7-fold). OLFM4 expression was correlated to IL-8 but
      not to Hath1. In controls immunostaining was restricted to the lower crypts but
      in inflamed IBD it expanded up to the epithelial surface including the mucus.
      OLFM4 bound to HBD1-3 without profoundly inactivating these defensins. In LS174T
      cells OLFM4 mRNA was significantly augmented after incubation with Escherichia
      coli K12, Escherichia coli Nissle and Bacteroides vulgatus. DBZ downregulated
      OLFM4 expression and blocked bacterial induction whereas IL-22 but not TNF-alpha
      was stimulatory. CONCLUSIONS: OLFM4 is overexpressed in active IBD and secreted
      into mucus. The induction is triggered by bacteria through the Notch pathway and
      also by the cytokine IL-22. OLFM4 seems to be of functional relevance in IBD as a
      mucus component, possibly by binding defensins.

PMID- 22398067
TI  - Corticosteroids and immunosuppressive therapy influence the result of QuantiFERON
      TB Gold testing in inflammatory bowel disease patients.
AB  - INTRODUCTION: Latent tuberculosis infection is detected by the tuberculin skin
      test before treating with anti-Tumour-Necrosis factor alpha (anti TNFalpha)
      reagents. More accurate are Interferon gamma release assays (IFNgamma release
      assays) to identify patients with latent tuberculosis. Because of a positive
      control in this assay, it is possible to identify those patients in which a
      result of tuberculosis testing is not available due to a lack of stimulation
      capacity of lymphocytes (indeterminate result). Patients suffering from IBD are
      often treated with immunosuppressive agents, which may influence the results of
      tuberculosis testing. AIM: The aim is to investigate the influence of
      immunosuppressive agents on the outcome of IFNgamma-release assay. METHODS: 50
      consecutive patients were documented before introducing anti-TNF-treatment in
      this single centre study between April 2009 and April 2010. Data of INFgamma
      release assay for latent tuberculosis, skin test and laboratory data and current
      medication were enrolled. RESULTS: For the period of one year data of 45
      consecutive patients was available for statistical analysis. 24 patients out of
      45 (corresponding to 53.3%) received at least low doses of corticoid treatment
      and 27 patients out of 45 (corresponding to 60.0%) received immunosuppressive
      agents. 13 patients out of 45 (corresponding to 28.9%) had an indeterminate
      result of the QuantiFERON test. A correlation between the indeterminate result
      and combination therapy of corticosteroids was found. The concomitant therapy of
      immunosuppressive agents lead to a lower IFN release but no significance was
      found. CONCLUSIONS: Steroid treatment and further combination therapy with
      immunosuppressive agents lead to a high risk of indeterminate QuantiFERON test.

PMID- 22398068
TI  - Monitoring inflammatory bowel disease activity: clinical activity is judged to be
      more relevant than endoscopic severity or biomarkers.
AB  - BACKGROUND: There is increasing evidence for the clinical relevance of mucosal
      healing (MH) as therapeutic treatment goal in inflammatory bowel disease (IBD).
      We aimed to investigate by which method gastroenterologists monitor IBD activity
      in daily practice. METHODS: A questionnaire was sent to all board-certified
      gastroenterologists in Switzerland to specifically address their strategy to
      monitor IBD between May 2009 and April 2010. RESULTS: The response rate was 57%
      (153/270). Fifty-two percent of gastroenterologists worked in private practice
      and 48% worked in hospitals. Seventy-eight percent judged clinical activity to be
      the most relevant criterion for monitoring IBD activity, 15% chose endoscopic
      severity, and 7% chose biomarkers. Seventy percent of gastroenterologists based
      their therapeutic decisions on clinical activity, 24% on endoscopic severity, and
      6% on biomarkers. The following biomarkers were used for IBD activity monitoring:
      CRP, 94%; differential blood count, 78%; fecal calprotectin (FC), 74%; iron
      status, 63%; blood sedimentation rate, 3%; protein electrophoresis, 0.7%; fecal
      neutrophils, 0.7%; and vitamin B12, 0.7%. Gastroenterologists in hospitals and
      those with <= 10 years of professional experience used FC more frequently
      compared with colleagues in private practice (P=0.035) and those with > 10 years
      of experience (P<0.001). CONCLUSIONS: Clinical activity is judged to be more
      relevant for monitoring IBD activity and guiding therapeutic decisions than
      endoscopic severity and biomarkers. As such, the accumulating scientific evidence
      on the clinical impact of mucosal healing does not yet seem to influence the
      management of IBD in daily gastroenterologic practice.

PMID- 22398069
TI  - A case report: ulcerative colitis, treatment with an antibody against tumor
      necrosis factor (infliximab), and subsequent liver necrosis.
AB  - In recent years, the use of antibodies against tumor necrosis factor alpha
      (TNFalpha) has expanded in rheumatology, gastroenterology, and dermatology. In
      addition to the more common side effects such as infections and hypersensitivity
      reactions, elevations of liver enzymes have been reported during anti-TNFalpha
      therapy, although severe liver failure has been extremely uncommon. This report
      describes a patient with severe liver failure after induction therapy with the
      TNFalpha antibody infliximab (Remicade(r)). A 46-year old female patient received
      two infusions of infliximab at a dose of 400 mg on weeks 0 and 8 for steroid
      dependent ulcerative colitis. Eight weeks after the second infusion, she suffered
      acute liver failure with necrosis, requiring liver transplantation.

PMID- 22398070
TI  - Primary tuberculous peritonitis during infliximab therapy for Crohn's disease.
AB  - A 64 year old male patient suffering from Crohn's disease received infliximab
      therapy for a period of 5 months prior to presentation to our hospital. Due to
      the symptoms fever, ascites, and diffuse abdominal tenderness on palpation of
      unknown origin, a CT scan of the abdomen was performed and led to the suspected
      diagnosis of a peritoneal carcinomatosis. QuantiFERONTM test revealed a
      tuberculosis infection and molecular analyses of a peritoneal specimen obtained
      by laparoscopy clearly identified Mycobacterium tuberculosis DNA. Quadruple
      tuberculostatic therapy was initiated and the patient's condition continuously
      improved thereafter.

PMID- 22398071
TI  - "Ulcerative crepitus" -- a case with subcutaneous emphysema and pneumomediastinum
      without colonic perforation or toxic megacolon in ulcerative colitis successfully
      treated conservatively.
AB  - A 19-year-old man with a 1-year history of ulcerative colitis presented with
      fever, bloody diarrhea and severe dehidration. He was on po.48 mg
      methylprednisolon and 3 g mesalazine daily, and has recently finished taking
      chlarythromycin for Campylobacter jejuni infection. On physical examination, no
      abdominal tenderness was found, but surprisingly, extensive bilateral
      subcutaneous emphysema was detected in the supraclavicular regions. Laboratory
      tests proved anaemia, elevated white blood cell count, thrombocyte count and CRP
      levels. Stool culture was negative. Chest X-ray and CT scan revealed
      pneumomediastinum and subcutaneous air on the neck spreading to the scapular
      regions. Besides blood transfusion, iv. cyclosporin therapy was initiated (200
      mg/day) along with iv. methylprednisolon (1mg/kg/day) and iv. ceftriaxon (2
      g/day). Stool frequency and bloody stools decreased remarkably within one week,
      and subcutaneous emphysema has resolved. Colonoscopy one week later revealed
      deep, extensive ulcerations in the transverse and descending colon without any
      sign of previous perforation. Cyclosporin and methylprednisolon was continued
      orally. Pneumomediastinum and subcutaneous emphysema in ulcerative colitis are
      unusual complications, typically linked to retroperitoneal colonic perforation or
      toxic megacolon, and are extremely rare without preceding endoscopic procedures.
      Except from two cases in the literature, conservative treatment with iv.
      antibiotics and steroids failed to save from urgent surgical procedure, resulting
      in a partial or total colectomy. In our case we were able to avoid urgent surgery
      by the immediate use of iv. cyclosporin in combination with iv. steroids and
      antibiotics, while the outcome of the bowel remains questionable in the next few
      months.

PMID- 22398072
TI  - Is patient reported outcome (PRO) affected by different follow-up regimens in
      inflammatory bowel disease (IBD)? A one year prospective, longitudinal comparison
      of nurse-led versus conventional follow-up.
AB  - OBJECTIVE: Specialist nurses have become increasingly involved in the management
      of Inflammatory Bowel Disease (IBD). The objectives of this study were to
      investigate the impact of nurse-led versus conventional follow-up on patient
      outcomes, such as quality of life, worries and time from relapse to start of
      treatment. METHODS: Patients completed the Short Form 36 (SF-36), Inflammatory
      Bowel Disease Questionnaire (N-IBDQ) and the Rating Form of IBD Patient Concerns
      (RFIPC) at baseline and after 1 year. Socio-demographic and clinical variables
      were obtained at V1 and V2. In addition the amount of e.g., relapses,
      hospitalisations, time from relapse to start of treatment, sick-leave,
      unscheduled visits or telephone calls was recorded during the follow-up period.
      RESULTS: A total of 140 patients were included; ulcerative colitis (UC) n=92,
      Crohn's disease (CD) n=48, mean age 46.9 and 40.0 years old, respectively. One
      hundred and thirty three patients attended the follow-up after 1 year. After 1
      year there were no differences between the groups in relation to quality of life,
      worries, amount of relapse, sick-leave, hospitalisations or surgery. Participants
      in nurse-led follow-up had a significantly (p<0.05) shorter interval from the
      start of a relapse to the start of treatment. CONCLUSIONS: Nurse-led follow-up of
      IBD patients produces PRO results comparable to that of gastroenterologists and
      may shorten the interval from the beginning of a relapse to the start of
      treatment.

PMID- 22398073
TI  - Anti chimeric antibodies against chimeric monoclonal antibodies may result in
      Kounis hypersensitivity associated acute coronary syndrome.

PMID- 22398074
TI  - Restoration of quality of life of patients with inflammatory bowel disease after
      one year with antiTNFalpha treatment.
AB  - BACKGROUND: Inflammatory bowel disease impairs patients' health related quality
      of life (HRQOL). AntiTNFalpha agents control disease activity effectively. An
      ambitious goal of treatment is to achieve the normalization of health. This can
      be assessed by using a cut-off scoring threshold of the IBDQ-36 questionnaire. It
      has not been established if antiTNFalpha treatment is able to restore to normal
      patients' HRQOL. AIMS: To determine whether patients with Crohn's disease (CD)
      and ulcerative colitis (UC) in clinical remission after one year treatment with
      antiTNFalpha agents achieve normalization of their HRQOL. METHODS: Observational
      and cross-sectional study in patients treated with antiTNFalpha for one year and
      in sustained clinical remission. Patients completed the specific questionnaire
      IBDQ-36. Complete restoration of health was considered achieved when global score
      of IBDQ-36 was higher than 209 points. RESULTS: 54 patients (43 with CD and 11
      with UC) were included. Thirty patients received adalimumab and 24 infliximab.
      Median global score of the IBDQ-36 was 231, without differences between CD and UC
      (228 vs 235 respectively, p=ns). Normalization of HRQOL was achieved in all 11 UC
      patients and in 29 out of 43 CD patients (67%). In our sample population,
      restoration of health was significantly more frequent in UC than in CD (p<0.05).
      CONCLUSIONS: One-year clinical remission induced by antiTNFalpha treatment
      restores perception of health to normal in most patients with IBD.

PMID- 22398075
TI  - Autoimmune hepatitis following treatment with infliximab for inflammatory bowel
      disease.

PMID- 22398076
TI  - Are positive serum-IgA-tissue-transglutaminase antibodies enough to diagnose
      coeliac disease without a small bowel biopsy? Post-test probability of coeliac
      disease.
AB  - BACKGROUND: It has been suggested that high titres of tTG are associated with
      elevated positive predictive values (PPV) for celiac disease. However, the PPV of
      a strongly positive tTG will depend on the celiac disease prevalence in the
      different risk groups of the disease AIMS: To assess the PPV of a strongly
      positive tTG for celiac disease. In addition, to calculate the post-test
      probability for celiac disease of a strongly positive tTG in a setting of routine
      clinical practice. METHODS: 145 consecutive celiac disease patients with positive
      tTG, and with a small bowel biopsy were included. The PPV for different cut-off
      points of tTG levels for the diagnosis of celiac disease was assessed. In
      addition, the cut-offs associated with higher PPV were used to calculate the
      positive likelihood ratio. A simulation in a setting of routine clinical practice
      was performed to calculate the post-test probability of celiac disease. RESULTS:
      No cut-off level was associated with a PPV of 100%. A cut-off of 80 U/mL
      (11.4*upper normal limit) was associated with the higher PPV value of 98.6%. In
      the most frequent clinical situations, which in general have a pre-test
      probability <10%, the post-test probability after having a strongly positive tTG
      was 90% or less. CONCLUSIONS: A strongly positive tTG should not be enough to
      diagnose celiac disease in the most frequent clinical situations, small bowel
      biopsy remaining as the gold standard in these cases.

PMID- 22398077
TI  - Development of a numerical index quantitating small bowel damage as detected by
      ultrasonography in Crohn's disease.
AB  - Small intestine contrast ultrasonography (SICUS) has emerged as a valuable tool
      in the detection of intestinal damage in Crohn's disease (CD). Our aim was to
      develop a numerical index quantitating small bowel damage as detected by SICUS in
      patients with an established diagnosis of CD. One hundred and ten patients with
      ileal or ileocolonic CD were prospectively enrolled and followed up for one year.
      Disease activity was assessed by CDAI and CRP levels. Study variables included
      bowel wall thickness, lumen diameter, lesion length and number of lesion site.
      Fistula, mesenteric adipose tissue alteration, abscess and lymphnodes were also
      considered. Bowel segments were considered as a hollow cylinder. Standardized
      variations of variables were combined into a statistical and mathematical model
      to create an algorithm scoring an index value ranging from 0 to 200. Index was
      subdivided into a severity scale with 5 classes from the lower (A) to the higher
      score (E). Median lesion index value was significantly higher (p<0.005) in
      patients with a CDAI>150 and in patients with CRP>5 mg/l (p=0.003). Patients
      classified in class E and D at SICUS underwent surgery within one year follow up
      more frequently than those in class C, B and A (p<0.0001). We propose a new index
      for assessment of small bowel lesions in CD (SLIC: sonographic lesion index for
      CD) developed by using SICUS. This index may turn ultrasonography in CD from a
      descriptive qualitative assessment to a quantitative numerical index suitable for
      comparison studies.

PMID- 22398078
TI  - Anti-TNF therapy induced immune neutropenia in Crohns disease- report of 2 cases
      and review of literature.
AB  - Transient neutropenia is reported in some patients on biologic therapy. We report
      two cases of severe neutropenia in patients with Crohn's disease following
      treatment with anti-TNF therapy. In both cases neutrophil specific granulocyte
      autoantibodies were detected during period of neutropenia and disappeared on
      cessation of anti-TNF therapy. These may indicate that anti-TNF agents may
      produce autoimmune agranulocytosis by triggering production granulocyte
      autoantibodies. The long term management strategy for patients with anti-TNF
      therapy induced autoimmune neutropenia is uncertain.

PMID- 22398079
TI  - Enteroendocrine cells in terminal ileal Crohn's disease.
AB  - BACKGROUND AND AIMS: Enteroendocrine cells sense gut luminal contents, and
      orchestrate digestive physiology whilst contributing to mucosal homeostasis and
      innate immunity. The terminal ileum is the key site of EEC expression but
      detailed assessment of their subtypes, lineage transcription factors and
      expression products has not been undertaken in terminal ileal Crohn's disease.
      Recent Crohn's disease gene wide association studies have linked the
      neuroendocrine transcription factor Phox2b; while autoantibodies to an
      enteroendocrine protein, ubiquitination protein 4a, have been identified as a
      disease behaviour biomarker. METHODS: Terminal ileal tissue from small or large
      bowel Crohn's disease and normal controls was analysed for enteroendocrine marker
      expression by immunohistochemistry and quantitative polymerase chain reaction.
      Inflammation was graded by endoscopic, clinical, histological and biochemical
      scoring. RESULTS: In small bowel disease, glucagon-like peptide 1 and
      chromogranin A cells were increased 2.5-fold (p=0.049) and 2-fold (p=0.031)
      respectively. Polypeptide YY cells were unchanged. Ileal enteroendocrine cell
      expression was unaffected in the presence of Crohn's colitis. Phox2b was co
      localised to enteroendocrine cells and showed a 1.5-fold increase in ileal
      disease. Significant mRNA increases were noted for chromogranin A (3.3-fold;
      p=0.009), glucagon-like peptide 1 (3.1-fold; p=0.007) and ubiquitination protein
      4a (2.2-fold; p=0.02). Neurogenin 3, an enteroendocrine transcription factor
      showed ~2 fold-upregulation (p=0.048). CONCLUSIONS: Enhanced enteroendocrine cell
      activity is present in small bowel disease, and observed in restricted cell
      lineages. This may impact on the epithelial immune response, cellular homeostasis
      and nutrient handling and influence appetite via increased satiety signalling in
      the gut-brain axis.

PMID- 22398080
TI  - Temporal trends in colon neoplasms in patients with primary sclerosing
      cholangitis and ulcerative colitis.
AB  - BACKGROUND AND AIM: Surveillance for colon cancer is recommended in patients with
      primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). It is unclear
      whether characteristics of colon neoplasia have changed over time. The aim of the
      study was to examine the temporal trends in colon neoplasia in patients with PSC
      and UC. METHODS: A total of 167 patients followed up at our institution between
      1985 and 2011, 55 of these with neoplasia detected on colonoscopic biopsy were
      identified. Characteristics of patients with colon neoplasia in PSC-UC were
      studied for two different time periods: 1985-1998 (early cohort) compared to 1999
      2011 (recent cohort). RESULTS: The median age at diagnosis of colon neoplasms was
      53 years (median IQR, 43-63). The baseline characteristics were similar in both
      cohorts. The colonic neoplasms that developed in PSC-UC patients were spread
      throughout the colon on colonoscopy, while there was predominant right sided
      distribution on colectomy in both cohorts. (81.7% vs. 18.3%, p<0.001) Compared to
      the recent cohort, both the PSC (17 vs. 11 years, p=0.02) and UC duration (20 vs.
      12 years, p=0.02) were longer in the early cohort. There were no differences in
      the grades and stages of cancer diagnosis. In addition, no differences in
      transplant-free survival or UC characteristics were revealed. CONCLUSIONS: With
      annual colonoscopic surveillance, dysplasia and cancer in patients with a
      combined diagnosis of PSC//UC is being diagnosed in patients with a shorter
      duration of these conditions. The nature and the location of neoplasia have,
      however, not changed.

PMID- 22398081
TI  - Treatment of Crohn's disease patients with infliximab is detrimental for the
      survival of Mycobacterium avium ssp. paratuberculosis within macrophages and
      shows a remarkable decrease in the immunogenicity of mycobacterial proteins.

PMID- 22398082
TI  - The requirements and barriers to successful transition of adolescents with
      inflammatory bowel disease: differing perceptions from a survey of adult and
      paediatric gastroenterologists.
AB  - BACKGROUND AND AIM: Preliminary data highlight the importance of appropriate
      transition for successful transfer of adolescents with IBD from paediatric to
      adult care. The aim of this study was to identify both the perceived needs of
      adolescent IBD patients and the barriers to successful transition from the
      perspective of professionals involved in their care. METHODS: A postal
      questionnaire was distributed to UK adult and paediatric gastroenterologists with
      an interest in IBD. The questionnaire utilised closed questions as well as ranked
      items on the importance of the various competencies of adolescents with IBD
      required for successful transition. RESULTS: Response rate of 62% and 49% for
      paediatric and adult gastroenterologists respectively was achieved. A structured
      transition service was perceived as very important by 80% paediatric compared to
      47% adult gastroenterologists (p=0.001). A higher proportion of adult than
      paediatric gastroenterologists identified inadequacies in the preparation of
      adolescents for transfer (79% and 42%, p=0.001). The main areas of perceived
      deficiency in preparation identified were patient lack of knowledge about the
      condition and treatment, lack of self advocacy and co-ordination of care. Lack of
      resources, clinical time, and a critical mass of patients were the factors ranked
      highest by both groups as barriers to transition care. Both adult (65%) and
      paediatric gastroenterologists (62%) highlighted suboptimal training in
      adolescent medicine for adult gastroenterologists. CONCLUSIONS: This survey
      highlights differences in the perception of adult and paediatric
      gastroenterologists in the management of transition care and perceived
      competencies for adolescents with IBD. Lack of training and inadequate resources
      are the main barriers identified for development of a successful transition
      service.

PMID- 22398083
TI  - Chronic hepatitis C, inflammatory bowel disease and interferon therapy.

PMID- 22398084
TI  - Cutaneous sarcoidosis in a patient with ulcerative colitis on infliximab.
AB  - The advance of anti-tumour necrosis factor (TNF) therapy had dramatically changed
      the treatment algorithm of inflammatory bowel disease (IBD). This had
      significantly improved the quality of life for patients with Crohn's disease (CD)
      and ulcerative colitis (UC).(1) However, side-effects of anti-TNF treatment were
      unavoidable with paradoxical inflammation (for example leucocytoclastic
      vasculitis and psoriasis) being well-known phenomena of anti-TNF therapy.(2) We
      report a case of infliximab induced cutaneous sarcoidosis in a patient with
      ulcerative colitis and review the literature.

PMID- 22398085
TI  - Vitamin D as a therapy for colitis: a systematic review.
AB  - BACKGROUND AND AIM: The effect of vitamin D supplementation on immune disorders
      has been a topical research focus. The aim of this systematic review was to
      examine the current evidence of the effect of vitamin D supplementation as a
      therapy for colitis. METHODS: The following databases were searched: MEDLINE,
      Pubmed, Scopus, Web of Knowledge, Cinicaltrials.gov and the Cochrane Central
      Register of Controlled Trials using the terms 'inflammatory bowel disease'
      'Crohn's disease' 'ulcerative colitis' 'colitis' [and] 'vitamin D'. Both human
      and animal studies published in English language were examined. The reference
      lists of included studies and review articles were manually searched for any
      relevant studies. RESULTS: Four studies were included in this systematic review.
      All reported an improvement in disease activity with vitamin D supplementation.
      The only high quality human study reported a non-significant reduction of relapse
      rate for Crohn's disease. No major adverse effects of vitamin D supplementation
      were reported. CONCLUSIONS: Although there is some evidence that supplemental
      vitamin D, as an adjunctive treatment, may help in controlling colitis, this
      evidence is not enough to justify using vitamin D in treating inflammatory bowel
      disease (IBD). Large high quality placebo-controlled randomised controlled trials
      are needed to explore a possible benefit of using vitamin D in treating IBD.

PMID- 22398086
TI  - On the zoonosis of M. avium subspecies paratuberculosis (MAP).

PMID- 22398087
TI  - Colorectal cancer screening and surveillance in Crohn's colitis.
AB  - AIMS: To assess colonoscopic screening and surveillance for detecting neoplasia
      in patients with long-standing colonic Crohn's disease (CD). PATIENTS AND
      METHODS: Colonoscopy and biopsy records from patients with colonic CD were
      evaluated at the Cedars-Sinai Inflammatory Bowel Disease Center during a 17-year
      period (1992-2009). RESULTS: Overall, 904 screening and surveillance examinations
      were performed on 411 patients with Crohn's colitis (mean 2.2 examinations per
      patient). The screening and surveillance examinations detected neoplasia in 5.6%
      of the patient population; 2.7% had low-grade dysplasia (LGD) (n=11), 0.7% had
      high-grade dysplasia (HGD) (n=3), and 2.2% had carcinoma (anal carcinoma n=3;
      rectal carcinoma n=6). Mean age of CD diagnosis was 25.6+/-0.8 years in those
      with normal examinations, compared to 17.7+/-2.7 years (p<0.001) in those with
      HGD, 36.85+/-1.43 in those with LGD (p=0.021) and 28.32+/-3.24 years in those
      with any dysplasia/cancer (p=0.034). Disease duration in patients with normal
      examinations was 19.1+/-0.5 years, compared to 36.8+/-4.4 years (p<0.001) in HGD,
      16.88+/-2.59 in those with LGD (p=0.253) and 30.68+/-4.03 years in those with any
      dysplasia/cancer (p=0.152). The mean interval between examinations was higher in
      HGD (31.5+/-9.4 months) compared to those with normal colonoscopies (12.92+/
      1.250 months; p=0.002). CONCLUSIONS: We detected cancer or dysplasia in 5.6% of
      patients with long-standing Crohn's colitis enrolled in a screening and
      surveillance program. Younger age at diagnosis of CD, longer disease course, and
      greater interval between exams were risk factors for the development of
      dysplasia.

PMID- 22398088
TI  - Risedronate improves bone mineral density in Crohn's disease: a two year
      randomized controlled clinical trial.
AB  - BACKGROUND: Patients with Crohn's disease have an increased frequency of
      osteopenia and osteoporosis. This randomized, controlled, double-blind study
      assessed the efficacy of risedronate versus placebo in treating low bone mineral
      density (BMD) in patients with Crohn's disease. METHODS: 88 Crohn's disease
      outpatients with BMD T-score<-1.0 by dual-energy X-ray absorptiometry were
      randomly assigned to one of two treatment groups for the two year study duration:
      one group received risedronate 35 mg weekly while another received placebo. Both
      groups received daily calcium (Ca; 500 mg) and vitamin D (D; 400 IU)
      supplementation. Percent change in BMD relative to baseline was compared between
      the two therapies at 12 and 24 months. RESULTS: Using intent-to-treat analysis,
      at 12 months, risedronate+Ca+D increased BMD, relative to baseline, more than
      placebo+Ca+D in the femoral trochanter (1.4+/-3.4% vs -0.1+/-3.1%; p=0.03) and
      total hip (1.1+/-2.7% vs -0.1+/-2.5%;p=0.04). This trend in greater BMD continued
      for the 24 month duration of the study. There was no difference between the two
      treatment groups for changes in spine BMD. Subgroup analysis revealed that
      risedronate+Ca+D resulted in significantly better improvement in femoral
      trochanter BMD in non-smokers (p=0.01), males (p=0.01), those with a history of
      corticosteroid use in the preceding year (p=0.01), and current users of
      immunosuppressants (p=0.04). CONCLUSIONS: Risedronate, in addition to daily
      calcium and vitamin D supplementation, is superior to calcium and vitamin D alone
      in improving femoral trochanter and total hip BMD in patients with Crohn's
      disease.

PMID- 22398089
TI  - Clumsy analogy yields melodramatic conclusion: MAP are not weapons of mass
      destruction.

PMID- 22398090
TI  - Maternal imprinting and female predominance in familial Crohn's disease.
AB  - BACKGROUND AND AIM: Although the genetic risk factors for familial and sporadic
      inflammatory bowel disease (IBD) seem identical, the relative risk for
      contracting IBD in the familial setting is larger as that seen in the population
      at large, suggesting an important role of epi- and/or paragenetic factors in
      familial IBD. Epidemiological data indicate a female predominance in IBD, but how
      this relates to familial IBD has not been assessed. METHODS: Familial IBD
      patients (N=608) were compared with a cohort of 415 sporadic IBD patients with
      regards to the patterns of sex and disease type distribution. The imprinting
      pattern in 87 families in which both a parent and a child had IBD was tested
      using Galton binominal statistics. RESULTS: The percentage of females in familial
      IBD population was significantly higher (61%; female/male ratio 1.5) compared
      with sporadic IBD (54%; female/male ratio 1.2; p=0.011). The analysis of
      offspring sex distribution pattern revealed significantly higher female to female
      transmission compared with female to male transmission rate (36 vs. 18,
      respectively; p=0.02). A significantly higher number of mother to child
      transmissions (55 vs. 32 of father to child transmissions) was observed
      (p=0.018). The female imprinting was specifically related to Crohn's disease (31
      vs. 14 mother vs. father to child transmissions, respectively; p=0.016).
      CONCLUSION: We propose that a female sex-specific epigenetic inheritance pattern
      for Crohn's disease is a major contributing factor in the family-specific risk in
      Crohn's disease. Sex-specific manifestation of familial Crohn's disease can
      partly explain the epidemiologically observed increased relative risk for females
      for contracting IBD.

PMID- 22398091
TI  - Surgical management of gluteal metastatic cutaneous Crohn's disease.
AB  - Metastatic cutaneous Crohn's disease is a rare entity first described by McCallum
      et al. in 1976. It is diagnosed when histologically characteristic granulomata
      are seen at a site not contiguous with inflammatory disease in the
      gastrointestinal tract. We herein report presentation, diagnosis and management
      of a 28 year old lady with disabling, symptomatic cutaneous Crohn's of the
      buttocks and natal cleft refractory to Infliximab therapy. To the best of our
      knowledge only four other adult cases have been reported in the literature of
      metastatic cutaneous Crohn's disease of the buttock area distant from a flexure
      or area of skin apposition. The differential diagnosis in this case was
      Hidradenitis Suppurativa. A good cosmetic result and excellent symptom control
      were achieved with extensive debridement, wide local excision, vacuum assisted
      closure and delayed skin grafting.

PMID- 22398092
TI  - Adherence of gastroenterologists to European Crohn's and Colitis Organisation
      consensus on Crohn's disease: a real-life survey in Spain.
AB  - BACKGROUND: There is no information as to the extent by which Spanish
      gastroenterologists adhere to Crohn's disease (CD) management guidelines. The
      objective of this study was to evaluate the degree of adherence of Spanish
      gastroenterologists to the European Crohn's and Colitis Organisation (ECCO)
      guidelines and to determine whether differences in adherence exist between
      gastroenterologists specialized in inflammatory bowel diseases (GSIBDs) and
      general gastroenterologists (GGs). METHODS: This was a prospective, nation-wide,
      questionnaire-based survey covering aspects related to diagnosis, treatment,
      follow-up, and safety considered by the physicians in their daily management of
      CD, as well as demographic traits seen in clinical practice. RESULTS: The overall
      degree of adherence to guidelines by both GSIBDs and GGs was high. However, the
      use of imaging techniques in diagnosis, follow-up, and in relapsed patients
      differed between the two groups. In the diagnosis of perianal disease, GSIBDs
      used magnetic resonance and surgical exploration under anesthesia more frequently
      than GGs. In terms of therapeutic choices, the adherence to guidelines was good
      in both groups. However, GSIBDs showed significantly higher adherence in some
      areas: thiopurines were used less in refractory cases and methotrexate was used
      more commonly in corticoid-dependent, azathioprine-intolerant patients, and in
      patients under biological treatment. Request for infection studies and
      vaccinations at diagnosis or prior to treatment was more common among GSIBDs.
      CONCLUSIONS: Guideline adherence among Spanish gastroenterologists is high.
      However, there are significant differences between IBD-specialized (more adherent
      in general) and non-specialized gastroenterologists.

PMID- 22398093
TI  - Low-dose smoking resumption in ex-smokers with refractory ulcerative colitis.
AB  - BACKGROUND AND AIM: Ulcerative colitis (UC) is primarily a disease of non
      smokers. Ex-smokers may have a more refractory disease course and anecdotal
      evidence in non-controlled clinical trials have suggested that smoking
      resumption, or the administration of nicotine, may ameliorate signs and symptoms
      of UC in ex-smokers. We report outcomes of ex-smokers with refractory UC who
      resumed low-dose cigarette smoking. METHODS: 17 ex-smokers with refractory UC
      were identified. Clinical remission was defined as a disease activity index score
      of 0. RESULTS: Two out of 17 patients refused the recommendation to resume
      smoking. Of the 15 patients who resumed smoking, the mean daily number of
      cigarettes was 8.6. Fourteen out of those 15 patients who resumed smoking were
      able to maintain prolonged clinical remission off steroids. One out of the 15
      patients failed to improve and required oral steroids. Another patient was
      compelled to quit smoking since he became addicted. His disease flared after
      maintaining a prolonged remission of 3 years and he eventually underwent surgery.
      Three out of these 15 patients switched from cigarettes smoking to nicotine
      compounds and continued to maintain remission. CONCLUSION: Resumption of low dose
      smoking in a selected group of ex-smokers with refractory UC may ameliorate signs
      and symptoms. Quality of life, medication side effects, and smoking risk factors
      should all be considered and discussed with patients. Smokers should be
      meticulously followed for compliance with "low-dose" regimen and all associated
      smoking risks.

PMID- 22398094
TI  - Long-term clinical impact of early introduction of granulocyte and monocyte
      adsorptive apheresis in new onset, moderately active, extensive ulcerative
      colitis.
AB  - BACKGROUND AND AIMS: The efficacy of granulocyte and monocyte adsorptive
      apheresis (GMA) for patients with a first episode of ulcerative colitis (UC) has
      been scarcely reported. This study was to see if the introduction of GMA at an
      early stage reduces corticosteroid administration and steroid dependency in the
      long term clinical course of UC. METHODS: Forty consecutive patients with
      moderately active symptoms as the first attack of UC were included. Twenty
      patients were treated with GMA, with or without corticosteroids (GMA group), and
      the other 20 were given corticosteroids without GMA (steroid group). All patients
      were monitored for 5 years. Relapses were treated in the same manner as the first
      attack in both groups. The total dose of steroid administered and the appearance
      of steroid-dependency were to be compared between the two groups. RESULTS: All
      patients in both groups achieved clinical remission after the first attack. The
      mean number of relapses per patient was 2.8 in the GMA group and 2.9 in the
      steroid group (P=0.86). During this study, 5 patients in the GMA group did not
      require corticosteroids. The mean dose of steroid administered during the 5 years
      was 2141 mg in the GMA group vs 5443 mg in the steroid group (P=0.002). One
      patient in the GMA group and 7 in the steroid group were steroid-dependent at the
      end of the study (P=0.048). CONCLUSIONS: In patients with the first UC episode,
      GMA therapy at an early stage significantly reduces steroid administration and
      steroid-dependency in the long-term clinical course.

PMID- 22398095
TI  - Infliximab-induced psoriasis during therapy for Crohn's disease.
AB  - Although therapy with tumor necrosis factor-alpha inhibitors (anti-TNF) provides
      beneficial effects in different immune inflammatory disorders, paradoxical cases
      of anti-TNF-induced psoriasis have increasingly been reported, mostly in the
      setting of rheumatologic diseases. To date, less than 50 cases of infliximab
      induced psoriasis in inflammatory bowel disease patients have been described. The
      present report was aimed at describing two new cases of infliximab-induced
      psoriasis during therapy for Crohn's disease and at carrying out a review on this
      intriguing phenomenon.

PMID- 22398096
TI  - Prevention of postoperative recurrence of Crohn's disease.
AB  - BACKGROUND: Up to 75% of patients with Crohn's disease (CD) will have intestinal
      resection during their life. Most patients will, however, develop postoperative
      recurrence (endoscopic, clinical or surgical). Several medical and surgical
      strategies have been attempted to prevent postoperative recurrence. This review
      evaluates the efficacy of different drug regimens and surgical techniques in the
      prevention of clinical, endoscopic and surgical postoperative recurrence of CD.
      METHODS: A literature search for randomized controlled trials on medical or
      surgical interventions was performed. The endpoints for efficacy were clinical,
      endoscopic and surgical recurrence. Meta-analyses were performed in case two or
      more RCTs evaluated the same drug or surgical technique. RESULTS: Mesalamine is
      more effective in preventing clinical recurrence than placebo (P=0,012), as well
      as nitroimidazolic antibiotics at one year follow-up (P<0.001) and thiopurines
      (P=0.018). Nitroimidazolic antibiotics are also more effective than placebo in
      preventing endoscopic recurrence (P=0.037), as well as thiopurines (P=0.015) and
      infliximab (P=0.006). Budenoside, probiotics, Interleukin-10 nor any of the
      different surgical procedures showed any significant difference compared to
      placebo in postoperative recurrence rates of CD. CONCLUSION: Among the different
      drug regimens and surgical techniques, only thiopurines and nitroimidazolic
      antibiotics are able to reduce postoperative clinical as well as endoscopic
      recurrence of CD. Mesalamine and infliximab also seem to be superior to placebo
      in preventing clinical recurrence and endoscopic recurrence, respectively. There
      is a paucity of trials evaluating long-term follow-up and prevention of surgical
      recurrence of CD.

PMID- 22398097
TI  - Prevalence and predictors of MRSA, ESBL, and VRE colonization in the ambulatory
      IBD population.
AB  - BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) patients may be at
      increased risk of acquiring antibiotic-resistant organisms (ARO). We sought to
      determine the prevalence of colonization of methicillin-resistant Staphylococcus
      aureus (MRSA), Enterobacteriaceae containing extended spectrum beta-lactamases
      (ESBL), and vancomycin-resistant enterococi (VRE) among ambulatory IBD patients.
      METHODS: We recruited consecutive IBD patients from clinics (n=306) and 3 groups
      of non-IBD controls from our colon cancer screening program (n=67), the family
      medicine clinic (n=190); and the emergency department (n=428) from the same
      medical center in Toronto. We obtained nasal and rectal swabs for MRSA, ESBL, and
      VRE and ascertained risk factors for colonization. RESULTS: Compared to non-IBD
      controls, IBD patients had similar prevalence of colonization with MRSA (1.5% vs.
      1.6%), VRE (0% vs. 0%), and ESBL (9.0 vs. 11.1%). Antibiotic use in the prior 3
      months was a risk factor for MRSA (OR, 3.07; 95% CI: 1.10-8.54), particularly
      metronidazole. Moreover, gastric acid suppression was associated with increased
      risk of MRSA colonization (adjusted OR, 7.12; 95% CI: 1.07-47.4). Predictive risk
      factors for ESBL included hospitalization in the past 12 months (OR, 2.04, 95%
      CI: 1.05-3.95); treatment with antibiotics it the past 3 months (OR, 2.66; 95%
      CI: 1.37-5.18), particularly prior treatment with vancomycin or cephalosporins.
      CONCLUSIONS: Ambulatory IBD patients have similar prevalence of MRSA, ESBL and
      VRE compared to non-IBD controls. This finding suggests that the increased MRSA
      and VRE prevalence observed in hospitalized IBD patients is acquired in-hospital
      rather than in the outpatient setting.

PMID- 22398098
TI  - Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine
      tolerant IBD patients on maintenance therapy.
AB  - BACKGROUND AND AIMS: Therapeutic drug monitoring of active metabolites of
      thiopurines, azathioprine and 6-mercaptopurine, is relatively new. The proposed
      therapeutic threshold level of the active 6-thioguanine nucleotides (6-TGN) is
      >=235 pmol/8*10(8) erythrocytes. The aim of this prospective cross-sectional
      study was to compare 6-TGN levels in adult thiopurine tolerant IBD patients with
      an exacerbation with those in remission, and to determine the therapeutic 6-TGN
      cut-off level. METHODS: Hundred IBD patients were included. Outcome measures were
      thiopurine metabolite levels, calculated therapeutic 6-TGN cut-off level,
      CDAI/CAI scores, thiopurine dose and TPMT enzyme activity. RESULTS: Forty-one
      patients had an exacerbation, 59 patients were in remission. In 17% of all
      patients 6-TGN levels were compatible with non-compliance. The median 6-TGN
      levels were not significantly different between the exacerbation and remission
      group (227 versus 263 pmol/8*10(8) erythrocytes, p=0.29). The previous reported
      therapeutic 6-TGN cut-off level of 235 pmol/8*10(8) erythrocytes was confirmed in
      this study. Twenty-six of the 41 patients (63%) with active disease had 6-TGN
      levels below this threshold and 24 of 59 IBD patients (41%) in clinical remission
      (p=0.04). CONCLUSIONS: Thiopurine non-compliance occurs frequently both in active
      and quiescent disease. 6-TGN levels below or above the therapeutic threshold are
      associated with a significant higher chance of IBD exacerbation and remission,
      respectively. These data support the role of therapeutic drug monitoring in
      thiopurine maintenance therapy in IBD to reveal non-compliance or underdosing,
      and can be used as a practical tool to optimize thiopurine therapy, especially in
      case of thiopurine non-response.

PMID- 22398099
TI  - Lewis Score: a useful clinical tool for patients with suspected Crohn's Disease
      submitted to capsule endoscopy.
AB  - BACKGROUND/AIMS: The Lewis Score (LS) can assess inflammatory activity on small
      bowel capsule endoscopy (SBCE). We aimed to evaluate the LS usefulness in the
      setting of suspected Crohn's Disease (CD). METHODS: Retrospective single-center
      study including 56 patients undergoing SBCE for suspected CD. Patients were
      divided into three groups, according to clinical presentation: Group 1 (28
      patients): suspected CD not supported by the International Conference on Capsule
      Endoscopy (ICCE) criteria; Group 2 (19 patients): suspected CD based on two ICCE
      criteria; Group 3 (9 patients): patients fulfilling three or more criteria.
      Inflammatory activity was assessed with the LS. The diagnosis of CD required a
      minimum follow-up of 6 months after SBCE, basing on clinical evaluation,
      endoscopic, histological, radiological, and/or biochemical investigations.
      RESULTS: SBCE detected significant inflammatory activity (LS>=135) in 23 patients
      (41.1%), being 5 patients from Group 1 (17.8%), 11 from Group 2 (57.9%) and 7
      from Group 3 (77.8%) (p<0.05). CD was diagnosed in 23 patients (41.1%): six
      patients from Group 1 (21.4%), 10 from Group 2 (52.6%) and 7 from Group 3 (77.8%)
      (p<0.05). CD was diagnosed in 82.6% of patients with significant inflammatory
      activity on CE (LS>=135), but in only 12.1% of those having a LS<135 (p<0.05).
      The LS Positive Predictive Value, Negative Predictive Value, Sensitivity and
      Specificity were 82.6%, 87.9%, 82.6% and 87.9%, respectively. CONCLUSIONS: The LS
      may be a valuable diagnostic tool in the setting of suspected CD. Patients not
      fulfilling the ICCE criteria have lower LS and fewer are diagnosed with CD during
      follow-up.

PMID- 22398100
TI  - Anaemia and iron deficiency in children with inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: Anaemia and iron deficiency are common in children with
      Inflammatory Bowel Disease (IBD) however it is not known if the prevalence of
      anaemia and iron deficiency alters following diagnosis. METHODS: Laboratory
      results from diagnosis, and at follow up one and two years later were recorded
      retrospectively in children with IBD recruited from a tertiary centre. Anaemia
      was defined using WHO standards and iron deficiency defined using published
      guidelines. RESULTS: 46 children (16 girls) with Crohn's disease and 34 children
      (18 girls) with UC were studied. 75% of children with IBD were anaemic at
      diagnosis, 30% were anaemic at follow up two years later. 90% of children with
      Crohn's and 95% of children with Ulcerative Colitis (UC) were iron deficient at
      diagnosis. At follow up two years later 70% of children with Crohn's and 65% of
      children with UC were iron deficient. CONCLUSIONS: Persistent anaemia and iron
      deficiency are common in childhood IBD, prevalence alters with duration of time
      from diagnosis.

PMID- 22398101
TI  - Cyclosporine or infliximab as rescue therapy in severe refractory ulcerative
      colitis: early and long-term data from a retrospective observational study.
AB  - INTRODUCTION: About 30-40% of patients with acute severe ulcerative colitis (UC)
      fail to respond to intensive intravenous (iv) corticosteroid treatment. Iv
      cyclosporine and infliximab are an effective rescue therapy in steroid-refractory
      UC patients but up to now it is still unclear which is the best therapeutic
      choice. METHODS: We reviewed our series of severe steroid-refractory colitis
      admitted consecutively since 1994 comparing two historical cohort treated with iv
      cyclosporine (2 mg/kg) or iv infliximab (5 mg/kg). The main outcome was the
      colectomy rate at 3 months, 12 months and at the end of the follow-up. RESULTS: A
      total of 65 patients were included: 35 in the cyclosporine group and 30 in the
      infliximab one. At 3 months the colectomy rate was 28.5% in the cyclosporine
      group and 17% in the infliximab group (p=0.25), while 48% versus 17% at 12 months
      (p=0.007, OR 4.7; 95% CI: 1.47-15.16). The 1-2-3 year cumulative colectomy rates
      were 48%, 54%, 57% in the cyclosporine group, and 17%, 23%, 27% in the infliximab
      group. At the end of the follow-up the colectomy rate was 60% versus 30% (p=0.04,
      HR 2.2; 95% CI: 1.11-4.86). High level of C reactive protein (p=0.04), extensive
      disease (p=0.01) and no azathioprine treatment (p<0.001) were related to the risk
      of colectomy. CONCLUSION: This study, despite being retrospective, indicates that
      both cyclosporine and infliximab are effective in avoiding a colectomy in steroid
      refractory UC patients. During the follow-up the risk of a colectomy is higher in
      patients treated with cyclosporine than with infliximab.

PMID- 22398102
TI  - Severity of primary sclerosing cholangitis and its impact on the clinical outcome
      of Crohn's disease.
AB  - BACKGROUND AND AIM: Crohn's disease (CD) is associated with primary sclerosing
      cholangitis (PSC). The aim of the study was to study the association between the
      severity of PSC and clinical outcome of CD, comparing the course of CD in
      patients with PSC not needing orthotopic liver transplantation (OLT) and those
      requiring OLT. METHODS: A total of 41 patients with PSC and CD seen at the
      Cleveland Clinic between 1985 and 2011 were included in this study. Clinical and
      demographic variables were obtained regarding the outcome of CD in patients with
      and without OLT. RESULTS: Patients with PSC-CD were divided into two groups: 20
      without OLT (non-OLT) and 21 with OLT. 18 (85.7%) of patients in the OLT group
      had pancolitis in contrast to 14 (70%) in the non-OLT group. (p=0.22). There were
      no significant differences regarding duration of CD, but the duration of PSC was
      longer in the OLT group [16.0+/-7.8 vs. 10.3+/-6.4, p=0.01]. The OLT and non-OLT
      groups did not differ in the number of CD flares [0 (0, 0) vs. 0 (0, 5), p=0.28)
      and need for surgery for CD [(6 (28.6%) vs. 9 (45%), p=0.27]. Colon carcinoma and
      dysplasia were similar in the non-OLT and OLT groups [(4 (20%) vs. 3 (13.2%),
      p=0.52]. On Cox regression analysis, OLT for PSC [Hazards ratio (HR) 1.2 (95%
      confidence interval (C.I.): 0.38-3.7, p=0.79] did not impact the risk of
      colectomy. CONCLUSIONS: In contrast to UC, severe PSC requiring OLT does not
      appear to impact the clinical outcome of CD.

PMID- 22398103
TI  - Lean body mass, physical activity and quality of life in paediatric patients with
      inflammatory bowel disease and in healthy controls.
AB  - BACKGROUND AND AIMS: Physical activity is important for muscle and bone strength
      in the growing child and may be impaired in paediatric patients with inflammatory
      bowel disease (IBD) even during quiescent disease. The SenseWearPro(2) armband
      allows to measure physical activity under everyday life conditions. METHODS:
      Thirty-nine IBD patients (27 Crohn's disease, 12 ulcerative colitis, 24 boys) in
      remission (n=26) or with only mild disease activity (n=13) were compared to 39
      healthy age and sex-matched controls. Body weight, height, body mass index (BMI),
      lean body mass as phase angle alpha (determined by bioelectrical impedance
      analysis), and dynamometric grip force were expressed as age- and sex-related Z
      scores. SenseWearPro(2) armbands were applied for three consecutive days to
      record number of steps, duration of physical activity and sleeping time. Quality
      of life was assessed with the German KINDL and IMPACT III questionnaires, energy
      intake with prospective food protocols. Differences between patients and pair
      matched controls were analysed by paired t-test. RESULTS: Patients showed lower Z
      scores for phase angle alpha (difference -0.72; 95% CI [-1.10; -0.34]) and lower
      grip strength (-1.02 [-1.58; -0.47]) than controls. They tended towards lesser
      number of steps per day (-1339 [-2760; 83]) and shorter duration of physical
      activity (-0.44 h [-0.94; 0.06]), particularly in females and patients with mild
      disease. Quality of life and energy intake did not differ between patients and
      controls. CONCLUSION: In spite of quiescent disease lean body mass and physical
      activity were reduced. Interventions to encourage physical activity may be
      beneficial in this lifelong disease.

PMID- 22398104
TI  - Relationships among hyperuricemia, endothelial dysfunction and cardiovascular
      disease: molecular mechanisms and clinical implications.
AB  - Uric acid is the end product of purine metabolism. Its immediate precursor,
      xanthine, is converted to uric acid by an enzymatic reaction involving xanthine
      oxidoreductase. Uric acid has been formerly considered a major antioxidant in
      human plasma with possible beneficial anti-atherosclerotic effects. In contrast,
      studies in the past two decades have reported associations between elevated serum
      uric acid levels and cardiovascular events, suggesting a potential role for uric
      acid as a risk factor for atherosclerosis and related diseases. In this paper,
      the molecular pattern of uric acid formation, its possible deleterious effects,
      as well as the involvement of xanthine oxidoreductase in reactive oxygen species
      generation are critically discussed. Reactive oxygen species contribute to
      vascular oxidative stress and endothelial dysfunction, which are associated with
      the risk of atherosclerosis. Recent studies have renewed attention to the
      xanthine oxidoreductase system, since xanthine oxidoreductase inhibitors, such as
      allopurinol and oxypurinol, would be capable of preventing atherosclerosis
      progression by reducing endothelial dysfunction. Also, beneficial effects could
      be obtained in patients with congestive heart failure. The simultaneous reduction
      in uric acid levels might contribute to these effects, or be a mere epiphenomenon
      of the drug action. The molecular mechanisms involved are discussed.

PMID- 22398105
TI  - Results of balloon dilatation of stenotic homografts in pulmonary position in
      children and young adults.
AB  - OBJECTIVES: To evaluate the results of balloon dilatation of stenotic homografts
      in children, adolescents, and young adults and to identify factors that might
      influence or predict the effect of the dilatation. BACKGROUND: Homografts are
      widely used in congenital cardiac surgery; however, the longevity remains a
      problem mostly because of stenosis in the homograft. The effect of treatment by
      balloon dilatation is unclear. METHODS: In a retrospective study, the effect of
      balloon dilatation was determined by the percentage of reduction of the peak
      systolic pressure gradient over the homograft during catheterisation and the
      postponement of re-intervention or replacement of the homograft in months.
      Successful dilatations - defined in this study as a reduction of more than 33%
      and postponement of more than 18 months - were compared with unsuccessful
      dilatations in search of factors influencing or predicting the results. RESULTS:
      The mean reduction of the peak systolic pressure gradient was 30% in 40
      procedures. Re-intervention or replacement of the homograft was postponed by a
      mean of 19 months. In all, 14 balloon dilatations (35%) were successful; the mean
      reduction was 49% and the mean postponement was 34 months. The time since
      homograft implantation, the presence of calcification, the homograft/balloon
      ratio, and the pressure applied during dilatation all tended to correlate with
      outcome, but were not statistically significant. CONCLUSIONS: Balloon dilatation
      is able to reduce the peak systolic pressure gradient over homografts in a
      subgroup of patients and can be of clinical significance to postpone re
      intervention or pulmonary valve replacement.

PMID- 22398106
TI  - A pragmatic randomised controlled trial to evaluate the cost-effectiveness of a
      physical activity intervention as a treatment for depression: the treating
      depression with physical activity (TREAD) trial.
AB  - OBJECTIVE: The TREAting Depression with physical activity (TREAD) study
      investigated the cost-effectiveness of a physical activity intervention, in
      addition to usual general practitioner care, as a treatment for people with
      depression. DESIGN: An individually randomised, pragmatic, multicentre randomised
      controlled trial with follow-up at 4, 8 and 12 months. A subset of participants
      took part in a qualitative study that investigated the acceptability and
      perceived benefits of the intervention. SETTING: General practices in the Bristol
      and Exeter areas. PARTICIPANTS: Aged 18-69 years with an International
      Statistical Classification of Diseases and Related Health Problems, 10th Edition
      (ICD-10) diagnosis of depression and scoring >= 14 on the Beck Depression
      Inventory (BDI). Those who were unable to complete self-administered
      questionnaires in English, with medical contraindications to physical activity or
      with psychosis, bipolar disorder or serious drug abuse were excluded.
      INTERVENTIONS: We devised an intervention designed to encourage choice and
      autonomy in the adoption of physical activity. It consisted of up to three face
      to-face and ten telephone contacts delivered by a trained physical activity
      facilitator over an 8-month period. MAIN OUTCOME MEASURES: The primary outcome
      was the BDI score measured at 4 months. Secondary outcomes included depressive
      symptoms over the 12 months and quality of life, antidepressant use and level of
      physical activity. RESULTS: The study recruited 361 patients, with 182 randomised
      to the intervention arm and 179 to the usual care arm; there was 80% retention at
      the 4-month follow-up. The intervention group had a slightly lower BDI score at 4
      months [-0.54, 95% confidence interval (CI) -3.06 to 1.99] but there was no
      evidence that the intervention improved outcome for depression. Neither was there
      any evidence to suggest a difference in the prescription of or self-reported use
      of antidepressants. However, the amount of physical activity undertaken by those
      who had received the intervention was increased (odds ratio 2.3, 95% CI 1.3 to
      3.9) and was sustained beyond the end of the intervention. From a health-care
      perspective, the intervention group was more costly than the usual care group,
      with the cost of the intervention L220 per person on average. It is therefore
      extremely unlikely that the intervention is cost-effective as a treatment for
      depression using current willingness-to-pay thresholds. CONCLUSIONS: This
      physical activity intervention is very unlikely to lead to any clinical benefit
      in terms of depressive symptoms or to be a cost-effective treatment for
      depression. Previous research has reported some benefit and there are three
      possible reasons for this discrepancy: first, even though the intervention
      increased self-reported physical activity, the increase in activity was not
      sufficiently large to lead to a measurable influence; second, only more vigorous
      activity might be of benefit; and third, previous studies had recruited
      individuals with a pre-existing commitment to physical activity. Future research
      is needed to identify and explain the mechanisms by which depression might be
      effectively treated, including, in particular, specific guidance on the optimum
      type, intensity and duration of physical activity required to produce a
      therapeutic effect. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16900744.
      FUNDING: This project was funded by the NIHR Health Technology Assessment
      programme and will be published in full in Health Technology Assessment; Vol. 16,
      No. 10. See the HTA programme website for further project information.

PMID- 22398107
TI  - A warning concerning the estimation of multinomial logistic models with
      correlated responses in SAS.
AB  - Kuss and McLerran in a paper in this journal provide SAS code for the estimation
      of multinomial logistic models for correlated data. Their motivation derived from
      two papers that recommended to estimate such models using a Poisson likelihood,
      which is according to Kuss and McLerran "statistically correct but
      computationally inefficient". Kuss and McLerran propose several estimating
      methods. Some of these are based on the fact that the multinomial model is a
      multivariate binary model. Subsequently a procedure proposed by Wright is
      exploited to fit the models. In this paper we will show that the new computation
      methods, based on the approach by Wright, are statistically incorrect because
      they do not take into account that for multinomial data a multivariate link
      function is needed. An alternative estimation strategy is proposed using the
      clustered bootstrap.

PMID- 22398109
TI  - Fibrillary glomerulonephritis presenting as rapidly progressive
      glomerulonephritis.
AB  - Fibrillary glomerulonephritis (GN) is an uncommon cause of rapidly progressive
      kidney failure. We report a case of rapidly progressive kidney failure with
      kidney biopsy showing crescentic GN on light microscopy and immunofluorescence
      showing linear/globular glomerular basement membrane (GBM) staining for
      immunoglobulin G and C3, consistent with anti-GBM disease. However, electron
      microscopy showed fibrillary deposits in the GBM, suggesting a diagnosis of
      fibrillary GN. As exemplified by this case, it is important to consider
      fibrillary GN in the differential diagnosis of crescentic GN with linear
      immunoglobulin G deposits within the GBM. Electron microscopy is crucial to make
      this diagnosis.

PMID- 22398108
TI  - Characteristics of renal cystic and solid lesions based on contrast-enhanced
      computed tomography of potential kidney donors.
AB  - BACKGROUND: The presence of a few renal cysts is considered of little relevance
      in healthy adults, although acquired renal cystic disease occurs in advanced
      kidney failure. The objective of this study was to detail renal cystic and solid
      lesions and identify any association with clinical characteristics. STUDY DESIGN:
      Clinical-pathologic correlation. SETTING & PARTICIPANTS: Potential kidney donors
      undergoing a standardized evaluation at the Mayo Clinic in 2000-2008. PREDICTORS:
      Age, kidney function, and chronic kidney disease risk factors. MEASUREMENTS:
      Renal cystic and solid lesions by contrast-enhanced computed tomographic images.
      OUTCOMES: Cyst number, diameter, and location. RESULTS: After excluding 8 with
      cystic disease, 7 of whom had autosomal dominant polycystic kidney disease, there
      were 1,948 potential kidney donors (42% men; mean age, 43 years). A cortical,
      medullary, or parapelvic cyst >=5 mm was present in 12%, 14%, or 2.8%. For ages
      19-49 years, 39%, 22%, 7.9%, and 1.6% had a cortical or medullary cyst >=2, >=5,
      >=10, and >=20 mm in diameter. For ages 50-75 years, 63%, 43%, 22%, and 7.8% had
      a cortical or medullary cyst >=2, >=5, >=10, and >=20 mm in diameter. The 97.5th
      percentile for number of cortical and medullary cysts >=5 mm increased with age
      (10 for men and 4 for women in the 60- to 69-year group). After age and sex
      adjustment, cortical and medullary cysts >=5 mm were associated with higher 24
      hour urine albumin excretion, as well as increased body surface area,
      hypertension, and higher glomerular filtration rate in some analyses.
      Angiomyolipomas, hyperdense cysts, and enhancing masses or cysts with concerning
      features for malignancy occurred in 2.2%, 1.2%, and 0.6% and were associated with
      older age (P <= 0.05 for each). LIMITATIONS: Persons with known chronic kidney
      disease were excluded. CONCLUSIONS: Renal cysts are common, particularly in older
      men, and may be a marker of early kidney injury because they associate with
      albuminuria, hypertension, and hyperfiltration.

PMID- 22398110
TI  - Evaluation of nutrient status after laparoscopic sleeve gastrectomy 1, 3, and 5
      years after surgery.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy evolved as a primary bariatric
      procedure with little information on its nutritional effects. Our objective was
      to assess the longer term micronutrient and vitamin status after laparoscopic
      sleeve gastrectomy at a university hospital. METHODS: Measurements of ferritin,
      iron, total iron binding capacity, hemoglobin, hematocrit, parathyroid hormone,
      albumin, calcium, magnesium, phosphorus, zinc, folate, and vitamins A, B1, B12,
      and D were obtained at baseline and 1, 3, and 5 years after surgery. Two-sample t
      tests with multiple adjusted comparisons and Fisher's exact test were used to
      determine deficiency. RESULTS: A total of 82 patients (67% women), with a mean
      age of 46.4 years and a baseline body mass index 55.7 kg/m2 were included in the
      present study (35 at 1, 27 at 3, and 30 at 5 years postoperatively). The
      percentage of excess body mass index loss was 58.5% at year 1 in 35 patients,
      63.1% at year 3 in 27 patients, and 46.1% at year 5 in 30 patients. The
      parathyroid hormone level decreased from 75.0 to 49.6 ng/mL in year 1 to 40.7
      ng/mL in year 3. The year 5 levels increased to 99.6 ng/mL. The mean vitamin D
      level increased from 23.6 ng/mL to 35.0, 32.1 and 34.8 at years 1, 3, and 5 (P =
      .05 for baseline to year 1). The vitamin D level was less than normal in 42% of
      the patients at year 5. After normalization from baseline, by year 5, parathyroid
      hormone had increased in 58.3% of patients. At year 5, vitamin B1 was less than
      normal in 30.8% of patients, and hemoglobin and hematocrit were less than normal
      in for 28.6% and 25% of patients, respectively. Finally, 28.9% of patients
      reported taking supplements in year 1, 42.9% in year 3, and 63.3% in year 5. The
      other variables were not significantly different. CONCLUSIONS: Laparoscopic
      sleeve gastrectomy resulted in health improvements through year 3. At year 5, the
      nutrient levels had reverted toward the baseline values. These observations
      provide focus for necessary clinical monitoring.

PMID- 22398111
TI  - Evaluation and treatment of patients with cardiac disease undergoing bariatric
      surgery.
AB  - BACKGROUND: Bariatric surgery is a proven tool in reducing the co-morbidities
      associated with morbid obesity. The aim of the present review was to assess the
      current data and discuss the strategies for preoperative evaluation, preoperative
      treatment, and intraoperative management of the obese patient with cardiac
      disease seeking bariatric surgery, including those who have undergone previous
      angiographic intervention with coronary stenting and/or antiplatelet therapy. The
      setting was a university hospital in the United States. METHODS: A search of the
      English-language reports using the keywords morbid obesity, bariatric surgery,
      perioperative risk assessment, coronary artery disease, coronary stents, and
      antiplatelet therapy was conducted. RESULTS: The methods of preoperative cardiac
      risk assessment found in the published studies included the use of certain
      criteria, stress echocardiography, and single-photon emission computed
      tomography. Preoperative medical treatment optimization with beta-blockers and
      statins is recommended. Perioperative antiplatelet therapy in the form of aspirin
      81 mg can be safely continued, but clopidogrel should be stopped and reinitiated
      with caution. CONCLUSION: Preoperative assessment of morbidly obese patients with
      coexisting cardiac issues presents unique challenges. Safe patient care and good
      clinical outcomes can be achieved with adherence to evidence-based practice.

PMID- 22398112
TI  - Improvement in health-related quality of life in first year after laparoscopic
      adjustable gastric banding.
AB  - BACKGROUND: We analyzed the health-related quality of life (HRQOL) and its
      determinants in the first year after laparoscopic adjustable gastric banding
      (LAGB). The setting was 10 Italian public and private bariatric surgery centers.
      METHODS: Data collected in an ongoing, prospective, 3-year multicenter Italian
      study on the changes in HRQOL after LAGB were used. HRQOL was investigated using
      the Medical Outcomes Study Short-Form 36 questionnaire. Hunger, satiety, and the
      self-perceived effects of LAGB were recorded. RESULTS: A total of 334 patients
      were enrolled. The follow-up rate was 92.2%. The percentage of excess weight loss
      was 39.6% +/- 25.8%, with very few side effects or complications. Hunger in the
      morning (0-10 scale) was 4.5 +/- 2.7 before surgery and 3.8 +/- 2.4 after 1 year
      (P <.001). Satiety after a meal (0-10 scale) was 7.1 +/- 2.7 before surgery and
      8.2 +/- 1.9 at 1 year (P <.001). The self-perceived effect of LAGB on caloric
      intake (0-10 scale) was 8.4 +/- 1.9 after 1 year. The scores for the 8 Medical
      Outcomes Study Short-Form 36 subscales were significantly improved after surgery.
      The physical component summary score was 52.6 +/- 11.9 at baseline and 79.1 +/-
      15.6 after 1 year (P <.001). The corresponding mental component summary scores
      were 52.2 +/- 12.3 and 76.5 +/- 17.2 (P <.001). Greater physical component
      summary improvement was independently associated with a low initial physical
      component summary (P <.001), high satiety (P = .002), a high percentage of excess
      weight loss (P = .013), and a high self-perceived effect of the LAGB (P = .026).
      Greater mental component summary improvement was associated with a low initial
      mental component summary (P <.001), high satiety (P <.001), a low frequency of
      heartburn (P = .004), and a high percentage of excess weight loss (P = .012).
      CONCLUSIONS: Significant improvements in HRQOL were observed in the first year
      after LAGB. A poor baseline HRQOL, a high efficacy of the banding in eating
      control, and better weight loss might influence HRQOL changes.

PMID- 22398115
TI  - In TIA or stroke patients with intracranial arterial stenosis, aggressive medical
      therapy was superior to percutaneous transluminal angioplasty and stenting for 30
      day risk of further stroke or death.

PMID- 22398113
TI  - Abnormal glucose tolerance testing after gastric bypass.
AB  - BACKGROUND: Symptoms secondary to dumping have been suggested to help patients
      refrain from simple carbohydrate ingestion after Roux-en-Y gastric bypass (RYGB).
      During follow-up examinations, we noted many patients with weight regain
      complaining of fatigue shortly after eating. Thus, we decided to study the
      glucose tolerance test (GTT) results in a cohort of post-RYGB patients. METHODS:
      A total of 63 RYGB patients, >6 months postoperatively, were studied with a GTT
      and measurement of insulin levels. The mean age was 48.5 +/- 10.8 years, mean
      preoperative body mass index was 49.0 +/- 6.5 kg/m(2), mean percentage of excess
      body mass index lost was 64.5% +/- 29.0%, mean weight regain at follow-up was
      11.6 +/- 12.4 lb, and mean follow-up period was 47.9 months. RESULTS: Of the 63
      patients, 49 had abnormal GTT results. Of the 63 patients, 6 were diabetic;
      however, only 1 of these patients had an elevated fasting glucose level. All 6
      patients were diabetic preoperatively. Of the 63 patients, 43 had evidence of
      reactive hypoglycemia at 1-2 hours after the glucose load. Of these patients, 22
      had a maximum/minimum glucose ratio >3:1, including 7 with a ratio >4:1.
      CONCLUSION: The results of the present study have demonstrated that an abnormal
      GTT result is a common finding after RYGB. Reactive hypoglycemia was found in 43
      of 63 patients, with insulin values that do not support nesidioblastosis. It is
      our hypothesis, that rather than preventing simple carbohydrate ingestion, the
      induced hypoglycemia that occurs might contribute to weight regain and
      maladaptive eating in certain post-RYGB patients.

PMID- 22398116
TI  - Preterm infants receiving heel lance procedures have slightly lower pain scores
      and quicker time to return to baseline heart rate when held in kangaroo care by
      the mother than by the father.

PMID- 22398117
TI  - Differences between electrically evoked compound action potential (ECAP) and
      behavioral measures in children with cochlear implants operated in the school age
      vs. operated in the first years of life.
AB  - OBJECTIVE: The aim of this study was to identify the differences in the NRT
      measures, behavioral measures, and their relationship between the group of
      congenitally deaf children operated in the first years of life and the group of
      children operated in the school age. METHODS: The study included 40 congenitally
      deaf children with cochlear implants divided into two groups. Group 1 was
      composed of 20 children (mean age at operation 2.3 years, range 1.4-4.6 years)
      and Group 2 was composed of 20 children (mean age at operation 11.3 years, range
      7.0-17.1 years). The ECAP was recorded using the Nucleus 24 neural response
      telemetry (NRT) system. In each child, the responses were evoked by the apical,
      middle and basal electrodes. The analyzed parameters were: the ECAP threshold (T
      NRT), N1P2 amplitude, N1 latency, slope of the amplitude growth function,
      response morphology, threshold (T-) level, maximum comfort (C-) level, dynamic
      range (DR), T-NRT as a percentage of the map DR, the correlation between the T
      NRT and the T- and C-levels. The recordings of parameters were performed two
      years after implantations. RESULTS: The T-NRT, DR, T-NRT as a percentage of the
      map DR and the correlation between T-NRT and C-levels were significantly
      different between both groups of children. There were no statistically
      significant differences between the groups with respect to the amplitude,
      latency, slope and morphology recorded using the same electrodes. However,
      intragroup differences regarding NRT measures and behavioral measures with
      respect to the position of stimulating electrode were more prominent in Group 2
      than in the Group 1. CONCLUSIONS: Results of this study have also found a great
      variability of NRT and MAP measures within and across patients in both groups of
      children, but it was still more pronounced in the group of school children. NRT
      profile across electrodes follows MAP profiles better in the Group 1 then in the
      Group 2. Overall findings of NRT and MAP measures are not consistent and
      unambiguous as we expected, but still suggest potential differences between
      results in children operated in first years of life, and those operated in school
      age.

PMID- 22398118
TI  - Acute bilateral blindness as a presenting symptom of Non-Hodgkin's lymphoma.
AB  - NHL usually presents with lymphadenopathy or symptoms related to compression by
      the primary tumor of surrounding structures. While the head and neck region is a
      common site of involvement, blindness is rarely a presenting symptom. We report
      here the case of a child who presented to the emergency room with acute bilateral
      loss of vision and no other symptoms. Cranial imaging studies revealed a solid
      mass of the skull base with compression on optic nerves. Diagnosis of Burkitt's
      lymphoma was confirmed after biopsy. The patient had partial vision improvement
      two days after optic nerve decompression which was done immediately at the night
      of presentation.

PMID- 22398119
TI  - Radiofrequency ablation of laryngeal saccular cyst in infants: a series of six
      cases.
AB  - Saccular cysts of larynx are uncommon entity. These are infrequent causes of
      respiratory obstruction in neonates and infants. The saccular cysts are thought
      to arise in the saccule of the ventricle as a result of atresia of the
      ventricular orifice. The treatment options used in the management of saccular
      cysts are endoscopic needle aspiration, marsupialization and endoscopic extended
      ventriculotomy. We have found that removal of the saccular cyst can be achieved
      relatively safely and effectively by endoscopic radiofrequency ablation with
      improved surgical precision and better healing. We share our experience with a
      series of six cases, diagnosed under the sedation, thereafter radiofrequency
      ablation of laryngeal saccular cysts was done.

PMID- 22398120
TI  - Atypical presentation of laryngeal tuberculosis in a pediatric patient.
AB  - Laryngeal tuberculosis is uncommon and most often associated with a primary lung
      infection in immunocompromised adults. We describe an atypical case in a
      pediatric patient with a relatively rapid onset and no history of travel or
      exposure to high-risk settings. Despite the unusual presentation and relative
      lack of familiarity with procedural guidelines in managing this uncommon and
      capricious disease by otolaryngologists in developed countries, reporting is
      mandated at multiple governmental health department levels. Consequently, this
      contagious entity must be considered in the interest of avoiding untoward
      outcomes for not only the patient, but the public as well.

PMID- 22398122
TI  - A unifying model for the analysis of phenotypic, genetic, and geographic data.
AB  - Recognition of evolutionary units (species, populations) requires integrating
      several kinds of data, such as genetic or phenotypic markers or spatial
      information in order to get a comprehensive view concerning the differentiation
      of the units. We propose a statistical model with a double original advantage:
      (i) it incorporates information about the spatial distribution of the samples,
      with the aim to increase inference power and to relate more explicitly observed
      patterns to geography and (ii) it allows one to analyze genetic and phenotypic
      data within a unified model and inference framework, thus opening the way to
      robust comparisons between markers and possibly combined analyses. We show from
      simulated data as well as real data that our method estimates parameters
      accurately and is an improvement over alternative approaches in many situations.
      The power of this method is exemplified using an intricate case of inter- and
      intraspecies differentiation based on an original data set of georeferenced
      genetic and morphometric markers obtained on Myodes voles from Sweden. A computer
      program is made available as an extension of the R package Geneland.

PMID- 22398121
TI  - The effect of geographical scale of sampling on DNA barcoding.
AB  - Eight years after DNA barcoding was formally proposed on a large scale, CO1
      sequences are rapidly accumulating from around the world. While studies to date
      have mostly targeted local or regional species assemblages, the recent launch of
      the global iBOL project (International Barcode of Life), highlights the need to
      understand the effects of geographical scale on Barcoding's goals. Sampling has
      been central in the debate on DNA Barcoding, but the effect of the geographical
      scale of sampling has not yet been thoroughly and explicitly tested with
      empirical data. Here, we present a CO1 data set of aquatic predaceous diving
      beetles of the tribe Agabini, sampled throughout Europe, and use it to
      investigate how the geographic scale of sampling affects 1) the estimated
      intraspecific variation of species, 2) the genetic distance to the most closely
      related heterospecific, 3) the ratio of intraspecific and interspecific
      variation, 4) the frequency of taxonomically recognized species found to be
      monophyletic, and 5) query identification performance based on 6 different
      species assignment methods. Intraspecific variation was significantly correlated
      with the geographical scale of sampling (R-square = 0.7), and more than half of
      the species with 10 or more sampled individuals (N = 29) showed higher
      intraspecific variation than 1% sequence divergence. In contrast, the distance to
      the closest heterospecific showed a significant decrease with increasing
      geographical scale of sampling. The average genetic distance dropped from > 7%
      for samples within 1 km, to < 3.5% for samples up to > 6000 km apart. Over a
      third of the species were not monophyletic, and the proportion increased through
      locally, nationally, regionally, and continentally restricted subsets of the
      data. The success of identifying queries decreased with increasing spatial scale
      of sampling; liberal methods declined from 100% to around 90%, whereas strict
      methods dropped to below 50% at continental scales. The proportion of query
      identifications considered uncertain (more than one species < 1% distance from
      query) escalated from zero at local, to 50% at continental scale. Finally, by
      resampling the most widely sampled species we show that even if samples are
      collected to maximize the geographical coverage, up to 70 individuals are
      required to sample 95% of intraspecific variation. The results show that the
      geographical scale of sampling has a critical impact on the global application of
      DNA barcoding. Scale-effects result from the relative importance of different
      processes determining the composition of regional species assemblages (dispersal
      and ecological assembly) and global clades (demography, speciation, and
      extinction). The incorporation of geographical information, where available, will
      be required to obtain identification rates at global scales equivalent to those
      in regional barcoding studies. Our result hence provides an impetus for both
      smarter barcoding tools and sprouting national barcoding initiatives-smaller
      geographical scales deliver higher accuracy.

PMID- 22398123
TI  - Effects of regular and highly fluoridated toothpastes in combination with saliva
      substitutes on artificial enamel caries lesions differing in mineral content.
AB  - OBJECTIVE: For patients with hyposalivation fluorides are supportive to prevent
      caries lesions. Remineralization of subsurface lesions might be improved by
      toothpastes containing 5000 MUgF(-)/g compared with those having 1400 MUgF(-)/g.
      This could be influenced by the degree of baseline mineralization. Therefore,
      this in vitro study evaluated the effects of fluoride toothpastes differing in
      fluoride concentration in combination with de- and remineralizing saliva
      substitutes using two lesion types. DESIGN: Specimens with shallow (SL; DeltaZ
      (SD): 1915 (543) vol% * MUm) or deep lesions (DL; 5804 (427) vol% * MUm) were
      either stored in mineral water [saturation with respect to octacalcium phosphate
      (S(OCP)): 0.5], demineralizing experimental (Exp, S(OCP): 0.3), demineralizing
      commercial (Glandosane, S(OCP): 0.3), or remineralizing saliva substitute
      (modified Saliva natura; S(OCP): 1.9) for five weeks (37  degrees C). Either one
      of three brushing procedures was performed additionally three times daily: no
      brushing, Elmex anticaries toothpaste (E; 1400 MUgF(-)/g), Duraphat toothpaste
      (D; 5000 MUgF(-)/g). Mineral parameters before and after storage were evaluated
      using microradiographs. RESULTS: Storage in Exp as well as Glandosane induced a
      significant demineralization (p < 0.05; relatively more pronounced in SL than
      DL). Additional brushing in particular with D reduced these effects. Storage
      alone in modified Saliva natura remineralized specimens (p < 0.05). CONCLUSIONS:
      Under the in vitro conditions chosen shallow lesions seem to be more susceptible
      for demineralization compared with deeper ones when stored in an undersaturated
      (with respect to OCP) saliva substitute. The highly fluoridated toothpaste seemed
      to be more beneficial than a regular one.

PMID- 22398124
TI  - Postural alpha suppression after sports head injury.

PMID- 22398125
TI  - Self-recognition and clonal selection: autoreactivity drives the generation of B
      cells.
AB  - The diversity of B cell receptor (BCR) specificities is generated by VDJ
      recombination of gene segments during early B cell development, a process which
      bears the risk of producing BCRs that recognize and lead to the destruction of
      self-structures. Traditional thoughts have mainly focused on how such putatively
      dangerous specificities are dealt with and in how they contribute to the
      development of autoimmune diseases. However, a positive or even necessary role of
      self-recognition during B cell development has rarely been taken into account.
      Now, considerable data reveal that the pre-B cell receptor (pre-BCR), which marks
      an important checkpoint during B cell development, acts as a surrogate
      autoreactive receptor. This review outlines how autoreactivity is necessary for
      efficient B cell development and how autoreactive receptors drive positive
      selection, leading to a diverse repertoire of receptor specificities in the
      mature B cell pool.

PMID- 22398126
TI  - Behavioral validation of avolition in schizophrenia.
AB  - BACKGROUND: Since Kraepelin, avolition, a core symptom of schizophrenia, has been
      defined as a decrease in spontaneous, self-initiated and purposeful behaviors
      observed in daily life activities. However, the concurrent validity of commonly
      used avolition measures has not been studied, and direct observation may offer a
      more objective way to measure avolition. METHOD: A direct observation measure of
      spontaneous and self-initiated behaviors that can be observed in an inpatient
      setting was defined with the use of time sampling method. This direct observation
      measure was used with fifty inpatients with schizophrenia. Additionally, patients
      were asked to rate their current interest in and their level of engagement in 10
      active behaviors during the preceding 7 days. Clinicians rated the patients'
      engagement in the same activities for the preceding 7 days as well. RESULTS: The
      direct observation measure showed very good psychometric properties. Three
      clinical negative symptom scales showed moderate to high correlation with the
      direct measure. Concerning the retrospective ratings, patients' self-assessments
      were poorly correlated with clinicians' ratings, but showed high correlation with
      their subjective interests. CONCLUSIONS: Clinical rating scales of negative
      symptoms show moderate to good concurrent validity as measures of avolition in
      schizophrenia. However, patients' self-reports do not appear to provide valid
      indices of avolition. Our results favor clinical negative symptoms scales that
      use observers' reports only, over patients' self-reports. The direct observation
      of patients' behavior offers a precise and objective measure of avolition that
      may be useful in drug challenges and clinical trials.

PMID- 22398127
TI  - Metformin for treatment of antipsychotic-induced weight gain: a randomized,
      placebo-controlled study.
AB  - OBJECTIVES: To evaluate the efficacy of metformin for treatment of antipsychotic
      induced weight gain. METHODS: Seventy-two patients with first-episode
      schizophrenia who gained more than 7% of their predrug weight were randomly
      assigned to receive 1000 mg/d of metformin or placebo in addition to their
      ongoing treatment for 12 weeks using a double-blind study design. The primary
      outcome was change in body weight. The secondary outcomes included changes in
      body mass index, fasting glucose and insulin, and insulin resistance index.
      RESULTS: Of the 72 patients who were randomly assigned, 66 (91.6%) completed
      treatments. The body weight, body mass index, fasting insulin and insulin
      resistance index decreased significantly in the metformin group, but increased in
      the placebo group during the 12-week follow-up period. Significantly more
      patients in the metformin group lost their baseline weight by more than 7%, which
      was the cutoff for clinically meaningful weight loss. Metformin was tolerated
      well by majority patients. CONCLUSION: Metformin was effective and safe in
      attenuating antipsychotic-induced weight gain and insulin resistance in first
      episode schizophrenia patients. Patients displayed good adherence to metformin.

PMID- 22398128
TI  - The contribution of thioredoxin-2 reductase and glutathione peroxidase to
      H(2)O(2) detoxification of rat brain mitochondria.
AB  - Brain mitochondria are not only major producers of reactive oxygen species but
      they also considerably contribute to the removal of toxic hydrogen peroxide by
      the glutathione (GSH) and thioredoxin-2 (Trx2) antioxidant systems. In this work
      we estimated the relative contribution of both systems and catalase to the
      removal of intrinsically produced hydrogen peroxide (H(2)O(2)) by rat brain
      mitochondria. By using the specific inhibitors auranofin and 1-chloro-2,4
      dinitrobenzene (DNCB), the contribution of Trx2- and GSH-systems to reactive
      oxygen species (ROS) detoxification in rat brain mitochondria was determined to
      be 60+/-20% and 20+/-15%, respectively. Catalase contributed to a non-significant
      extent only, as revealed by aminotriazole inhibition. In digitonin-treated rat
      hippocampal homogenates inhibition of Trx2- and GSH-systems affected
      mitochondrial hydrogen peroxide production rates to a much higher extent than the
      endogenous extramitochondrial hydrogen peroxide production, pointing to a strong
      compartmentation of ROS metabolism. Imaging experiments of hippocampal slice
      cultures showed on single cell level substantial heterogeneity of hydrogen
      peroxide detoxification reactions. The strongest effects of inhibition of
      hydrogen peroxide removal by auranofin or DNCB were detected in putative
      interneurons and microglial cells, while pyramidal cells and astrocytes showed
      lower effects. Thus, our data underline the important contribution of the Trx2
      system to hydrogen peroxide detoxification in rat hippocampus. This article is
      part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC
      2012).

PMID- 22398129
TI  - Antinociceptive effects of low dose lumbosacral epidural ropivacaine in healthy
      ponies.
AB  - The objective of this study was to evaluate the safety and efficacy of low dose
      lumbosacral epidural ropivacaine in ponies. Antinociceptive effects of epidural
      ropivacaine were evaluated by means of mechanical nociceptive thresholds (MNTs)
      at several spinal levels in conscious ponies. The effects of ropivacaine on
      nociceptive afferent transmission to the spinal cord were also assessed by
      measuring spinal cord somatosensory evoked potentials (SSEPs) in anaesthetised
      ponies. Ataxia scores were determined in conscious ponies to assess the effects
      on motor function. A randomised, placebo controlled, double blind cross-over
      design was used. Low dose lumbosacral epidural ropivacaine led to increases in
      MNTs at various anatomical locations with a maximum effect at the lumbosacral and
      sacrococcygeal regions, both with respect to increase in threshold and duration
      of effect. Analysis of SSEPs showed that epidural ropivacaine influenced both
      Abeta- and Adelta-mediated afferent transmission to the spinal cord at the level
      of the lumbosacral junction. Ponies showed mild ataxia after low dose lumbosacral
      epidural ropivacaine, but all ponies remained standing. Application of low dose
      lumbosacral epidural ropivacaine provided safe and efficacious antinociceptive
      effects in conscious and anaesthetised ponies, and could therefore be a valuable
      addition to multimodal analgesic protocols in Equidae.

PMID- 22398130
TI  - Use of comparative proteomics to identify the effects of creatine pyruvate on
      lipid and protein metabolism in broiler chickens.
AB  - Four hundred male chickens were selected to study the effects of pyruvate (Pyr),
      creatine pyruvate (CrPyr) and creatine (Cr) on the expression of hepatic
      mitochondrial and cytoplasm proteins associated with lipid and protein
      metabolism. Mitochondrial purification was accomplished using the two-step
      differential centrifugation and density gradient method, and the activities of
      organelle-specific marker enzymes were determined to assess the purity of the
      mitochondria. Proteins were extracted and fractionated by two-dimensional
      electrophoresis and the differential protein spots were assessed by matrix
      assisted laser desorption/ionization-time of flight mass spectrometry. CrPyr
      reduced fatty acid accumulation by down-regulating adipose differentiation
      related protein, inhibited ATP synthase expression, and reduced cholesteryl ester
      transfer protein (CETP) expression, thus reducing the levels of high density
      lipoprotein and triglycerol (TG) levels (thereby lowering fat and cholesterol
      deposition). CrPyr increased the expression of eukaryotic translation initiation
      factor (eIF) 2B, calreticulin (CRT) and eIF3a, thus promoting protein synthesis.
      CrPyr up-regulated the expression of fatty acid-binding proteins, CETP and
      apolipoprotein A-IV in cytoplasmic extracts, and these proteins accelerated the
      decomposition of fatty acids and TG, thus reducing fat deposition. In conclusion,
      CrPyr plays an important role in lipolysis and protein synthesis, and this effect
      was more pronounced than was the effect of Pyr and Cr.

PMID- 22398131
TI  - Canine parvovirus in Australia: the role of socio-economic factors in disease
      clusters.
AB  - To identify clusters of canine parvoviral related disease occurring in Australia
      during 2010 and investigate the role of socio-economic factors contributing to
      these clusters, reported cases of canine parvovirus were extracted from an on
      line disease surveillance system. Reported residential postcode was used to
      locate cases, and clusters were identified using a scan statistic. Cases included
      in clusters were compared to those not included in such clusters with respect to
      human socioeconomic factors (postcode area relative socioeconomic disadvantage,
      economic resources, education and occupation) and dog factors (neuter status,
      breed, age, gender, vaccination status). During 2010, there were 1187 cases of
      canine parvovirus reported. Nineteen significant (P<0.05) disease clusters were
      identified, most commonly located in New South Wales. Eleven (58%) clusters
      occurred between April and July, and the average cluster length was 5.7 days. All
      clusters occurred in postcodes with a significantly (P<0.05) greater level of
      relative socioeconomic disadvantage and a lower rank in education and occupation,
      and it was noted that clustered cases were less likely to have been neutered
      (P=0.004). No significant difference (P>0.05) was found between cases reported
      from cluster postcodes and those not within clusters for dog age, gender, breed
      or vaccination status (although the latter needs to be interpreted with caution,
      since vaccination was absent in most of the cases). Further research is required
      to investigate the apparent association between indicators of poor socioeconomic
      status and clusters of reported canine parvovirus diseases; however these initial
      findings may be useful for developing geographically- and temporally-targeted
      prevention and disease control programs.

PMID- 22398132
TI  - Overexpression of P-glycoprotein, STAT3, phospho-STAT3 and KIT in spontaneous
      canine cutaneous mast cell tumours before and after prednisolone treatment.
AB  - Prednisolone is a glucocorticoid (GC) commonly used in the treatment of canine
      mast cell tumours (MCTs); however, resistance to GCs develops in many MCTs
      following repeated treatment. P-glycoprotein (P-gp), signal transducer and
      activator of transcription 3 (STAT3) and KIT (CD117) are involved in GC
      resistance. The aim of this study was to evaluate the response to prednisolone
      treatment in canine cutaneous MCTs and to investigate the levels of P-gp, STAT3,
      phospho-STAT3 (pSTAT3) and KIT proteins in MCTs with or without prednisolone
      treatment. Immunohistochemistry was performed on tumour samples from 41 dogs with
      cutaneous MCTs. The overall objective response rate (including complete and
      partial responses) was 51.8% for dogs treated with prednisolone; poorly
      differentiated or higher stage MCTs had a lower response rate. The median time
      span of tumours to reach maximal tumour regression was 14 d (range 3-77 d); 22
      (81.5%) reached maximal regression at 21 d. The majority of MCTs overexpressed
      both P-gp and STAT3 before and after prednisolone treatment. Reduced expression
      of pSTAT3 and alterations in the KIT expression pattern were observed in MCTs
      post-treatment. Prednisolone treatment that caused a marked reduction in tumour
      volume was correlated with reduced pSTAT3 expression. A cytoplasmic KIT staining
      pattern was correlated with a lower tumour response rate to prednisolone
      treatment.

PMID- 22398133
TI  - [3T tractography imaging: anatomy and clinical applications].
AB  - Tractography (TG) is the only non-invasive technique that enables the fibres of
      the white substance to be dissected. This technique can study the projection,
      association, and commissural fibres, and is an improvement and an important
      complement to conventional MR imaging. TG is an important tool for preoperative
      sub-cortical mapping, and there is a good correlation between TG and the direct
      sub-cortical stimulation technique. TG can have false positives in regions
      infiltrated by the tumour or with a mass effect. Furthermore, a negative TG does
      not exclude functional fibre persistence. TG is capable of demonstrating changes
      in other pathologies (congenital malformations, ischaemic disease and
      demyelinating diseases).

PMID- 22398134
TI  - [Case 45. Sarcoidosis with testicular involvement].

PMID- 22398137
TI  - Optimized efficient liver T(1rho) mapping using limited spin lock times.
AB  - T(1rho) relaxation has recently been found to be sensitive to liver fibrosis and
      has potential to be used for early detection of liver fibrosis and grading. Liver
      T(1rho) imaging and accurate mapping are challenging because of the long scan
      time, respiration motion and high specific absorption rate. Reduction and
      optimization of spin lock times (TSLs) are an efficient way to reduce scan time
      and radiofrequency energy deposition of T(1rho) imaging, but maintain the near
      optimal precision of T(1rho) mapping. This work analyzes the precision in T(1rho)
      estimation with limited, in particular two, spin lock times, and explores the
      feasibility of using two specific operator-selected TSLs for efficient and
      accurate liver T(1rho) mapping. Two optimized TSLs were derived by theoretical
      analysis and numerical simulations first, and tested experimentally by in vivo
      rat liver T(1rho) imaging at 3 T. The simulation showed that the TSLs of 1 and 50
      ms gave optimal T(1rho) estimation in a range of 10-100 ms. In the experiment, no
      significant statistical difference was found between the T(1rho) maps generated
      using the optimized two-TSL combination and the maps generated using the six TSLs
      of [1, 10, 20, 30, 40, 50] ms according to one-way ANOVA analysis (p = 0.1364 for
      liver and p = 0.8708 for muscle).

PMID- 22398136
TI  - Dissociating visual form from lexical frequency using Japanese.
AB  - In Japanese, the same word can be written in either morphographic Kanji or
      syllabographic Hiragana and this provides a unique opportunity to disentangle a
      word's lexical frequency from the frequency of its visual form - an important
      distinction for understanding the neural information processing in regions
      engaged by reading. Behaviorally, participants responded more quickly to high
      than low frequency words and to visually familiar relative to less familiar
      words, independent of script. Critically, the imaging results showed that visual
      familiarity, as opposed to lexical frequency, had a strong effect on activation
      in ventral occipito-temporal cortex. Activation here was also greater for Kanji
      than Hiragana words and this was not due to their inherent differences in visual
      complexity. These findings can be understood within a predictive coding framework
      in which vOT receives bottom-up information encoding complex visual forms and top
      down predictions from regions encoding non-visual attributes of the stimulus.

PMID- 22398138
TI  - Knee kinetic pattern during gait and anterior knee pain before and after
      rehabilitation in patients with patellofemoral pain syndrome.
AB  - Patellofemoral pain is likely due to compressive force acting on the patella
      related in turn to knee extension moment. The latter variable was assumed to be
      (i) reduced during short-distance free walking in case of patellofemoral pain
      syndrome and (ii) increased after therapeutic pain reduction. Peak knee extension
      moment at beginning of stance phase was recorded by three-dimensional gait
      analysis in 22 controls and in 23 patients with patellofemoral pain syndrome
      before and after rehabilitation of knee extensors and flexors to reduce the pain.
      Pain would occur mainly in stressful activities such as stair negotiation or
      squatting and was quantified by the anterior knee pain scale. Peak knee extension
      moment was significantly reduced in all the patients before treatment (n=23)
      compared to controls, although no one had pain during free walking. In the 17
      patients who experienced significant post-rehabilitation pain reduction in their
      stressful activities, the peak knee extension moment was significantly reduced
      before treatment compared to controls and significantly increased after
      treatment, reaching values similar to control values. The peak knee extension
      moment during free walking appears to be a good kinetic variable related to a
      compensatory mechanism limiting or avoiding anterior knee pain and may be of
      interest in assessing knee dynamics alteration in patients with PFPS.

PMID- 22398139
TI  - Pulmonary metastatic chordoma improved by platinum-based chemotherapy.
AB  - Chordomas are rare, low-grade, primary malignant bone tumors that are locally
      invasive and frequently recur. Despite the provision of radical excision as a
      primary treatment, local recurrences ultimately develop in most patients with
      chordoma. For these reasons, postoperative therapy such as radiation therapy is
      often required. However, the chemotherapy, as the treatment of chordoma relapse,
      has not only limited experiences but also considerable controversy on its
      effectiveness. In addition, in the case of pulmonary nodules, it is difficult to
      diagnose or suspect pulmonary metastatic chordoma initially due to its rarity and
      similar histologic features to other malignancies. Herein, we present an
      interesting case of metastatic chordoma in a 52-year old woman, which has been
      well controlled by platinum-based chemotherapy.

PMID- 22398140
TI  - Single-catheter radiofrequency ablation of a permanent junctional reciprocating
      tachycardia in a premature neonate.
AB  - A 34-week premature neonate presented with drug-refractory permanent junctional
      incessant tachycardia and haemodynamic compromise. The patient underwent
      successful radiofrequency catheter ablation using a single-catheter approach. The
      child remains in sinus rhythm, without pharmacological treatment, 2 years after
      the procedure.

PMID- 22398141
TI  - Assessing public attitudes on the retention and use of residual newborn screening
      blood samples: a focus group study.
AB  - This paper discusses attitudes and opinions of a diverse group of participants
      toward the retention and use of residual newborn blood samples for research. Data
      were drawn from focus groups based in six states in the USA, and results provide
      support for the retention and use of residual newborn blood samples for research
      when parental permission is asked beforehand. However, there were a number of
      concerns that also warrant attention for the development of policy and
      maintaining trust with the public, such as timing of permission, use of samples
      already stored, level of personal control of sample use and education. The
      results demonstrate the complexity of the topic and the ethical ambiguities
      associated with the retention and use of residual newborn blood samples.

PMID- 22398142
TI  - Does attachment insecurity affect the outcomes of a multidisciplinary pain
      management program? The association between attachment insecurity, pain,
      disability, distress, and the use of opioids.
AB  - Cognitive and behavioural treatments have been shown to be effective for the
      management of chronic pain. However, not all patients succeed at such a
      treatment. Attachment insecurity has recently been proposed as an individual
      vulnerability factor that may have a negative impact on pain, disability,
      psychological distress, and compliance with treatment, resulting in a poorer
      outcome. Furthermore, attachment avoidance has been associated with opioid abuse.
      We hypothesised that attachment anxiety would be associated with higher levels of
      pain intensity and disability, and that both attachment dimensions would be
      associated with anxiety and depression. Moreover, we hypothesised that attachment
      avoidance would be positively associated with the use of opioids. Finally, we
      predicted that patients with an insecure attachment orientation would profit less
      from a routine pain management program. Data were collected from 72 patients
      referred consecutively from December 2008 to August 2009 to a 13-week pain
      management program at a Danish multidisciplinary pain centre. Both attachment
      dimensions were positively associated with anxiety and depression. Moreover, the
      insecurely attached patients used significantly more opioids compared to the
      securely attached. None of the attachment dimensions was associated with pain and
      disability, and the pain management program was equally effective for both the
      secure and insecure groups. However, the level of anxiety and depression for
      insecurely attached patients did not decline below a clinical level post
      treatment. The present study suggests that attachment insecurity plays an
      important role in the context of chronic pain management. With regards to the
      management of pain related anxiety, depression, and the use of opioids, the
      current results suggests that practitioners should keep attachment insecurity in
      mind.

PMID- 22398143
TI  - Tracing the origins of successful aging: the role of childhood conditions and
      social inequality in explaining later life health.
AB  - This study investigates the role of childhood conditions and social inequality in
      older Europeans' propensity to age successfully, controlling for later life risk
      factors. Successful aging was assessed following Rowe and Kahn's
      conceptualization, using baseline interviews from the first two waves of the
      Survey of Health, Ageing and Retirement in Europe (SHARE). These data were merged
      with retrospective information on participants from 13 Continental European
      countries, collected as part of the SHARELIFE project. Our sample consists of
      22,464 men and women, who are representative of the non-institutionalized
      population aged 50 or older (mean age: 63.3) in their respective country.
      Estimating multilevel logistic models, we controlled for demographics (age, sex),
      childhood conditions (SES, health, cognition), later life risk factors (various
      dimensions of SES and health behaviors), as well as social inequality (measured
      by country-specific Gini coefficients). There is an independent association of
      childhood living conditions with elders' odds of aging well. Higher parental SES,
      better math and reading skills, as well as self-reports of good childhood health
      were positively associated with successful aging, even if contemporary
      characteristics were controlled for. Later life SES and health behaviors
      exhibited the expected correlations with our dependent variable. Moreover, lower
      levels of income inequality were associated with a greater probability of meeting
      Rowe and Kahn's successful aging criteria. We conclude that unfavorable childhood
      conditions exhibit a harmful influence on individuals' chances to age well across
      all European welfare states considered in this study. Policy interventions should
      thus aim at improving the conditions for successful aging throughout the entire
      life course.

PMID- 22398145
TI  - Role of ComEA in DNA uptake during transformation of competent Bacillus subtilis.
AB  - The role of the competence protein ComEA in DNA uptake during transformation of
      competent Bacillus subtilis was analyzed by lysed-protoplast transformation (LP
      transformation). A comEA deletion mutant was constructed by a fusion polymerase
      chain reaction. Transformants of the mutant were obtained by LP transformation at
      a frequency of 1.1 * 10(2) transformants per MUg DNA, representing a low relative
      efficiency of transformation [RET (mutant/wild type)] of 2.7 * 10(-6). This
      implied an important role of the protein during DNA uptake. When analyzing LP
      transformation of comEA with a plasmid (5.7 kb), a similar RET (mutant/wild type)
      of 5.6 * 10(-5) was obtained. Following addition of DNA into the comEA mutant
      culture, the number of transformants increased at a rate of 0.5
      transformants/min, which was very low compared with the wild-type (6.9*10(4)
      transformants/min). However, even in the comEA mutant, DNA uptake began
      immediately after addition of DNA. Using co-transformation analysis of the comEA
      mutant, short linkages at distances of 2-156 kb could be detected, but not long
      linkages at distances of 671-1662 kb. Taken together, the results indicate that
      ComEA plays an important role in the transfer of transforming DNA into the DNA
      channel and in controlling the rate of DNA uptake.

PMID- 22398147
TI  - Gender discrimination in undernutrition with mediating factors among Bengalee
      school children from Eastern India.
AB  - This study was undertaken to determine age and sex variations in the prevalence
      of underweight and stunting, and to assess the impact of some socio-economic
      variables on undernutrition among 6-16 year old school children of Bengalee
      ethnicity in Chapra, West Bengal, India. The subjects were selected randomly from
      various schools and madrassas of the Chapra Block. A total of 725 children (342
      boys and 383 girls) aged 6-16 years were measured and data on their socio
      economic status were collected. Age and sex combined rates of underweight and
      stunting were 44.40% and 37.20%, respectively. Weight-for-age Z-score (WAZ)
      showed significant association with per-capita income (PCI) among boys (F=5.45)
      and girls (F=8.14). Height-for-age Z-score (HAZ) has also shown the association
      with per-capita income among boys (F=4.43) and girls (F=9.69). The WAZ was
      significantly associated with fathers' educational status (FOS) (t=-2.95) and the
      number of living rooms (NLR) (t=-2.91) among girls. The HAZ showed significant
      association with number of siblings (NS) among girls (F=4.25). Linear regression
      analyses revealed that NLR (t=2.04) and NS (t=1.95) had a significant impact on
      HAZ among boys. Among girls, PCI (t=3.38), FOS (t=2.87) and NLR (t=2.81) had a
      significant impact on WAZ and also PCI (t=3.28) and FOS (t=2.90) had a
      significant impact on HAZ. NLR had significant associations with underweight
      (chi(2)=3.59) and stunting (chi(2)=4.20) among boys. Among girls, PCI had
      significant associations with underweight (chi(2)=11.15) and stunting
      (chi(2)=11.64). FOS also showed significant associations with underweight
      (chi(2)=8.10) as well as stunting (chi(2)=8.28) among girls. NLR showed a
      significant association with underweight (chi(2)=7.75). Logistics regression
      analyses revealed that FOS (Wald=8.00) and NLR (Wald=4.09) were significant
      predictors of stunting among boys. Among girls, PCI was a significant predictor
      of underweight (Wald=10.95) as well as stunting (Wald=10.45). FOS, NLR and NS
      were also significant predictors of stunting (Wald=8.16), underweight (Wald=7.68)
      and stunting (Wald=6.97) respectively. The present study revealed that the
      nutritional status of the children was unsatisfactory and it is of paramount
      importance not only to increase the amount of food supplementation given but also
      to promote gender equality.

PMID- 22398146
TI  - Hypoxia-inducible factors: mediators of cancer progression and targets for cancer
      therapy.
AB  - Hypoxia-inducible factors (HIFs) mediate adaptive physiological responses to
      hypoxia. In human cancers that are accessible for O(2) electrode measurements,
      intratumoral hypoxia is common and severe hypoxia is associated with increased
      risk of mortality. HIF activity in regions of intratumoral hypoxia mediates
      angiogenesis, epithelial-mesenchymal transition, stem-cell maintenance, invasion,
      metastasis, and resistance to radiation therapy and chemotherapy. A growing
      number of drugs have been identified that inhibit HIF activity by a variety of
      molecular mechanisms. Because many of these drugs are already FDA-approved for
      other indications, clinical trials can (and should) be initiated to test the
      hypothesis that incorporation of HIF inhibitors into current standard-of-care
      therapy will increase the survival of cancer patients.

PMID- 22398148
TI  - Mesenchymal stem cells delivered in a microsphere-based engineered skin
      contribute to cutaneous wound healing and sweat gland repair.
AB  - BACKGROUND: Bone-marrow-derived mesenchymal stem cells (BM-MSCs) can contribute
      to wound healing after skin injury. However, the role of BM-MSCs on repairing
      skin appendages in renewal tissues is incompletely explored. Moreover, most
      preclinical studies suggest that the therapeutic effects afforded by BM-MSCs
      transplantation are short-lived and relatively unstable. OBJECTIVE: To assess
      whether engrafted bone-marrow-derived mesenchymal stem cells via a delivery
      system can participate in cutaneous wound healing and sweat-gland repair in mice.
      METHODS: For safe and effective delivery of BM-MSCs to wounds, epidermal growth
      factor (EGF) microspheres were firstly developed to both support cells and
      maintain appropriate stimuli, then cell-seeded microspheres were incorporated
      with biomimetic scaffolds and thus fabricated an engineered skin construct with
      epithelial differentiation and proliferative potential. The applied efficacy was
      examined by implanting them into excisional wounds on both back and paws of hind
      legs in mice. RESULTS: After 3 weeks, BM-MSC-engineered skin (EGF loaded) treated
      wounds exhibited accelerated healing with increased re-epithelialization rates
      and less skin contraction. Furthermore, histological and immunofluorescence
      staining analysis revealed sweat glands-like structures became more apparent in
      BM-MSC-engineered skin (EGF loaded) treated wounds but the number of implanted BM
      MSCs were decreased gradually in later phases of healing progression.
      CONCLUSIONS: Our study suggests that BM-MSCs delivered by this EGF microspheres
      based engineered skin model may be a promising strategy to repair sweat glands
      and improve cutaneous wound healing after injury and success in this study might
      provide a potential benefit for BM-MSCs administration clinically.

PMID- 22398149
TI  - Bioactivity of tea tree oil from Melaleuca alternifolia against sheep lice
      (Bovicola ovis Schrank) in vitro.
AB  - Tea tree oil (TTO) from the Australian native plant Melaleuca alternifolia has
      wide ranging bio-active properties, including insecticidal and repellent activity
      against arthropods. Furthermore, composition of commercially available Australian
      TTO is specified under an International Organization for Standardization standard
      (ISO 4730), reducing the potential for variable effects often noted with
      botanical pesticides. The effect of TTO, meeting the ISO standard for terpinen-4
      ol chemotype, was tested against sheep lice (Bovicola ovis Schrank) in a series
      of laboratory studies. Immersion of wool for 60s in formulations containing
      concentrations of 1% TTO and above caused 100% mortality of adult lice and eggs.
      Exposure to vapours from TTO, delivered as droplets in fumigation chambers and
      when applied to wool also caused high mortality in both lice and eggs. The main
      active component of TTO in the fumigant tests was terpinen-4-ol. Treated surface
      assays and tests with wool where the formulation was allowed to dry before
      exposure of lice indicated low persistence. These studies demonstrate that TTO is
      highly toxic to sheep lice and active at concentrations that suggest potential
      for the development of TTO-based ovine lousicides.

PMID- 22398150
TI  - Poor psychological health and stressful-life events are more common in
      adolescents with self-harm thoughts or episodes.

PMID- 22398151
TI  - Self-perception and rumination in social anxiety.
AB  - The present study examined the relationship between perceptions of performance
      and post-event processing (PEP) following task feedback in individuals with
      social phobia and matched control participants. Groups of high and low socially
      anxious participants engaged in a structured 5-min conversation in groups of four
      people. Following the conversation, false feedback (given in the form of either
      high scores or moderate scores) was given and self-appraisals of performance,
      levels of positive and negative mood, and levels of PEP were assessed. Results
      showed that participants' perceptions of their own performance and levels of
      positive affect significantly predicted the degree to which they engaged in
      negative rumination about the task. The moderate score condition was found to be
      detrimental for socially anxious individuals' self-appraisals and PEP, whereas
      controls showed no significant difference in self-appraisal and PEP, regardless
      of feedback. The results are discussed in relation to current cognitive models of
      social phobia and both treatment implications and directions for future research
      are explored.

PMID- 22398152
TI  - Weight suppression as a predictor of weight gain and response to intensive
      behavioral treatment in patients with anorexia nervosa.
AB  - Previous studies have documented that weight suppression (a person's highest
      adult weight minus current weight) predicts weight gain and disordered eating
      symptoms during treatment of bulimia spectrum disorders, but no research has
      examined weight suppression in individuals with anorexia nervosa (AN). Thus, this
      study sought to characterize weight suppression in a large sample of patients
      with AN (N = 185), and to evaluate whether weight suppression at admission for
      intensive behavioral treatment predicts weight gain and clinical outcomes at
      discharge. Weight suppression varied from 0 kg to 78 kg (M [SD] = 17.1 [10.8] kg)
      in AN patients. Higher levels of weight suppression predicted greater total
      weight gain, a faster rate of weight gain, and bulimic symptoms during intensive
      treatment even after controlling for body mass index on admission, length and
      type of intensive treatment received, restricting versus binge-eating/purging AN
      subtype, and other predictors of study outcomes. These findings converge with
      previous research documenting the clinical significance of weight suppression in
      the treatment of eating disorders. Future work is needed to replicate the current
      findings, and examine whether weight suppression predicts the course of AN
      following discharge from intensive treatment.

PMID- 22398153
TI  - Internet-based parent management training: a randomized controlled study.
AB  - OBJECTIVE: The current study evaluated the efficacy of an Internet-based parent
      training program for children with conduct problems. Dose-response ratio and
      costs for the program were also considered. METHOD: Parents of 104 children (aged
      3-12 years) were randomly allocated to either parent training or a waitlist
      control condition. Diagnostic assessment was conducted at baseline and parent
      ratings of child externalizing behaviors and parent strategies were completed
      before and after treatment and at 6-month follow-up. RESULTS: At post-treatment
      assessment, children whose parent(s) had received the intervention showed a
      greater reduction in conduct problems compared to the waitlist children. Between
      group intent-to-treat effect sizes (Cohen's d) on the Eyberg Intensity and
      Problem scales were .42 and .72, respectively (study completers .66 and 1.08). In
      addition, parents in the intervention group reported less use of harsh and
      inconsistent discipline after the treatment, as well as more positive praise.
      Effects on behavior problems were maintained at 6-month follow-up. CONCLUSIONS:
      The results support the efficacy of parent training, administered through
      Internet, with outcomes comparable to many of the group-based parent training
      programs. The efficacy, low cost, and higher accessibility make this intervention
      a fitting part in a stepped-care model.

PMID- 22398154
TI  - Expression and purification of recombinant type IV fimbrial subunit protein of
      Pasteurella multocida serogroup B:2 in Escherichia coli.
AB  - Pasteurella multocida serogroup B:2, a causative agent of haemorrhagic
      secpticaemia (HS) in cattle and buffalo especially in tropical regions of Asia
      and African countries, is known to possess a type IV fimbriae (pili) as one of
      the virulent factors. In the present study, ptfA gene encoding for type IV
      fimbrial subunit of P. multocida serogroup B:2 (strain p52), an Indian HS vaccine
      strain, has been cloned and over-expressed in recombinant Escherichia coli. The
      recombinant type IV fimbrial subunit protein (~31 kDa) including N-terminus
      histidine tag was purified under denaturing condition and confirmed by western
      blotting. A homology model of HS causing P. multocida serogroup B:2 fimbrial
      subunit has also been discussed. The study indicated the potential possibilities
      to use the recombinant fimbrial protein in developing HS subunit vaccine along
      with suitable adjuvant.

PMID- 22398155
TI  - Application of a whole-body pharmacokinetic model for targeted radionuclide
      therapy to NM404 and FLT.
AB  - We have previously developed a model that provides relative dosimetry estimates
      for targeted radionuclide therapy (TRT) agents. The whole-body and tumor
      pharmacokinetic (PK) parameters of this model can be noninvasively measured with
      molecular imaging, providing a means of comparing potential TRT agents. Parameter
      sensitivities and noise will affect the accuracy and precision of the estimated
      PK values and hence dosimetry estimates. The aim of this work is to apply a PK
      model for TRT to two agents with different magnitudes of clearance rates, NM404
      and FLT, explore parameter sensitivity with respect to time and investigate the
      effect of noise on parameter precision and accuracy. Twenty-three tumor bearing
      mice were injected with a 'slow-clearing' agent, (124)I-NM404 (n = 10), or a
      'fast-clearing' agent, (18)F-FLT (3'-deoxy-3'-fluorothymidine) (n = 13) and
      imaged via micro-PET/CT pseudo-dynamically or dynamically, respectively. Regions
      of interest were drawn within the heart and tumor to create time-concentration
      curves for blood pool and tumor. PK analysis was performed to estimate the mean
      and standard error of the central compartment efflux-to-influx ratio
      (k(12)/k(21)), central elimination rate constant (k(el)), and tumor influx-to
      efflux ratio (k(34)/k(43)), as well as the mean and standard deviation of the
      dosimetry estimates. NM404 and FLT parameter estimation results were used to
      analyze model accuracy and parameter sensitivity. The accuracy of the
      experimental sampling schedule was compared to that of an optimal sampling
      schedule found using Cramer-Rao lower bounds theory. Accuracy was assessed using
      correlation coefficient, bias and standard error of the estimate normalized to
      the mean (SEE/mean). The PK parameter estimation of NM404 yielded a central
      clearance, k(el) (0.009 +/- 0.003 h(-1)), normal body retention, k(12)/k(21)
      (0.69 +/- 0.16), tumor retention, k(34)/k(43) (1.44 +/- 0.46) and predicted
      dosimetry, D(tumor) (3.47 +/- 1.24 Gy). The PK parameter estimation of FLT
      yielded a central elimination rate constant, k(el) (0.050 +/- 0.025 min(-1)),
      normal body retention, k(12)/k(21) (2.21 +/- 0.62) and tumor retention,
      k(34)/k(43) (0.65 +/- 0.17), and predicted dosimetry, D(tumor) (0.61 +/- 0.20
      Gy). Compared to experimental sampling, optimal sampling decreases the dosimetry
      bias and SEE/mean for NM404; however, it increases bias and decreases SEE/mean
      for FLT. For both NM404 and FLT, central compartment efflux rate constant, k(12),
      and central compartment influx rate constant, k(21), possess mirroring
      sensitivities at relatively early time points. The instantaneous concentration in
      the blood, C(0), was most sensitive at early time points; central elimination,
      k(el), and tumor efflux, k(43), are most sensitive at later time points. A PK
      model for TRT was applied to both a slow-clearing, NM404, and a fast-clearing,
      FLT, agents in a xenograft murine model. NM404 possesses more favorable PK values
      according to the PK TRT model. The precise and accurate measurement of k(12),
      k(21), k(el), k(34) and k(43) will translate into improved and precise dosimetry
      estimations. This work will guide the future use of this PK model for assessing
      the relative effectiveness of potential TRT agents.

PMID- 22398156
TI  - Does congenital heart disease severely jeopardise family life and pregnancies?
      Obstetrical history of women with congenital heart disease in a single tertiary
      centre.
AB  - AIM: Women with congenital heart disease are often considered to be restricted in
      their obstetrical life and even their marital life. Our single-centre study aimed
      to determine the real-life situation of these women with regard to successful
      family life and any pregnancy complications they may experience. METHODS: From
      our database of adults with congenital heart disease, 160 of 178 women completed
      a questionnaire and had their files reviewed. They were classified into three
      groups according to their pregnancy risk - "good condition" group, no pregnancy
      restriction; "at-risk" group, pregnancy allowed with close follow-up at a
      tertiary centre; and "contraindicated" group, pregnancy inadvisable. RESULTS: The
      proportion of women in a relationship was 46% with no difference between the
      three groups. In the groups where pregnancy was allowed, 55% of women conceived a
      child. The total incidence of spontaneous abortion was 21%. The rate of caesarean
      section was 15%. The incidence of cardiac failure was 4.7%, arrhythmia 1.2%,
      endocarditis 1.2%, hypertension 2.4%, and preeclampsia 1.2%. Foetal complications
      included prematurity and/or low birth weight (9.5%) and one foetal malformation
      (0.82%). CONCLUSION: Women with severe congenital heart disease are willing to
      start a family and are successful in this enterprise. Although the complication
      rate during pregnancy in congenital heart disease remains high, with good
      monitoring these pregnancies occur without severe complications and a low rate of
      medical abortion or caesarean section.

PMID- 22398157
TI  - Exhaled breath condensate collection in the mechanically ventilated patient.
AB  - Collection of exhaled breath condensate (EBC) is a non-invasive means of sampling
      the airway-lining fluid of the lungs. EBC contains numerous measurable mediators,
      whose analysis could change the management of patients with certain pulmonary
      diseases. While initially popularized in investigations involving spontaneously
      breathing patients, an increasing number of studies have been performed using EBC
      in association with mechanical ventilation. Collection of EBC in mechanically
      ventilated patients follows basic principles of condensation, but is influenced
      by multiple factors. Effective collection requires selection of a collection
      device, adequate minute ventilation, low cooling temperatures, and sampling times
      of greater than 10 min. Condensate can be contaminated by saliva, which needs to
      be filtered. Dilution of samples occurs secondary to distilled water in vapors
      and humidification in the ventilator circuit. Dilution factors may need to be
      employed when investigating non-volatile biomarkers. Storage and analysis should
      occur promptly at -70  degrees C to -80  degrees C to prevent rapid degradation
      of samples. The purpose of this review is to examine and describe methodologies
      and problems of EBC collection in mechanically ventilated patients. A
      straightforward and safe framework has been established to investigate disease
      processes in this population, yet technical aspects of EBC collection still exist
      that prevent clinical practicality of this technology. These include a lack of
      standardization of procedure and analysis of biomarkers, and of normal reference
      ranges for mediators in healthy individuals. Once these procedural aspects have
      been addressed, EBC could serve as a non-invasive alternative to invasive
      evaluation of lungs in mechanically ventilated patients.

PMID- 22398158
TI  - Cognitive behavioural intervention for adults with anxiety complications of
      asthma: prospective randomised trial.
AB  - BACKGROUND: High levels of asthma-related fear and panic exacerbate asthma
      symptoms and complicate the management of asthma. Asthma-specific fear may be
      reduced by a cognitive behavioural intervention. We aimed to test if there is a
      reduction in asthma-specific fear after cognitive behavioural intervention
      compared with routine treatment. METHODS: Adults with asthma registered with
      family doctors in Sheffield UK were screened for anxiety and 94 highly anxious
      patients were randomly allocated to receive either a cognitive behavioural
      intervention to improve self-management of their anxiety (n = 50) or routine
      clinical care (n = 44). Asthma-specific fear at the end of treatment and at six
      month follow up were the primary endpoints. Service usage in the six months prior
      to and six months following the intervention was monitored to allow estimation of
      costs. Data were analysed by intention to treat. FINDINGS: At the end of
      treatment, there was a significantly greater reduction in asthma-specific fear
      for people in the CBT group compared with controls. At six months after treatment
      the reduction in asthma-specific fear in the CBT group was increased and the
      difference between treatment and control group was statistically significant.
      Service use costs were not reduced in the CBT group. INTERPRETATION: A brief
      cognitive behavioural intervention was found to have efficacy in reducing asthma
      specific panic fear immediately after treatment and at 6 months follow up. There
      was no cost advantage to cognitive behavioural treatment.

PMID- 22398159
TI  - A double blind randomized cross over trial comparing rate of decortication and
      efficacy of intrapleural instillation of alteplase vs placebo in patients with
      empyemas and complicated parapneumonic effusions.
AB  - AIM: A double blind randomized cross over trial to compare the rate of
      decortication, safety and efficacy of intrapleural instillation of Alteplase vs.
      Placebo in empyema and complicated parapneumonic effusions (CPE). METHODS:
      Patients diagnosed with empyema or CPE and considered for surgery were given the
      option to enter into this trial. Intrapleural instillation of the 'Drug' was
      given daily for three days. Patient that failed the first arm of the trial were
      offered surgery or to cross over to the second arm. Failure was documented if
      pleural effusions did not improve by 50% on CT scans after three doses of the
      'Drug' or if these effusions recurred within six weeks. RESULTS: One hundred and
      eight patients were evaluated and one hundred enrolled in the trial. 32 patients
      were excluded, 29 for noninfectious loculated effusions, two for protocol
      violation and one for bleeding at chest tube site. There were 17 patients with
      empyema and 51 patients with CPE. 58 of the 61 patients (26 crossed over) with
      empyema/CPE resolved with Alteplase therapy compared to 4 of the 32 patients (one
      crossed over) treated with Placebo (p value <0.001). None of the patients went to
      surgery. Adverse events with Alteplase therapy compared to Placebo were not
      statistically significant, with chest pain and bleeding complications being the
      most common. CONCLUSION: Intrapleural instillation of Alteplase is significantly
      more effective than Placebo in patients with empyema and PPE (95% vs.12%). This
      study demonstrates it is safe and efficacious with minimal adverse reactions.

PMID- 22398160
TI  - Time course and predictors for cancer-related fatigue in a series of
      oropharyngeal cancer patients treated with chemoradiation therapy.
AB  - BACKGROUND: Cancer-related fatigue (CRF) is a highly prevalent and underestimated
      symptom in cancer patients. This study aims to analyze CRF solely in a cohort of
      oropharyngeal cancer patients who underwent treatment with radiotherapy (RT).
      METHODS: In January 2008 to June 2010, 87 consecutive oropharyngeal carcinoma
      patients underwent definitive RT. Concurrent chemotherapy was used for 94% of
      patients. The median prescription dose to the planning target volume of the gross
      or clinical tumor volume was 70 Gy for definitive cases (n = 84) and 66 Gy for
      postoperative cases (n = 3), both delivered over 6.5 weeks. A normalized 12-point
      numeric rating scale assessed CRF from patient visits before, during, and after
      RT. RESULTS: The median follow-up of living patients was 14 months. Fatigue
      peaked 1-2 weeks post-RT and remained higher than baseline for up to 2 years post
      RT in 50% of patients. The average fatigue score at the time of completion of
      therapy or maximum thereafter up to 1 year post-RT was significantly worse than
      baseline. Patients who experienced pain had a trend toward significance with
      association for a higher maximum difference in fatigue from baseline. Karnofsky
      performance status score, weight change, and mood disorders did not correlate
      with CRF. CONCLUSIONS: Fatigue was a common treatment-related symptom in this
      uniform cohort of patients with oropharyngeal cancer. RT was highly correlated
      with worsening of CRF. Pain control has the potential to help mitigate CRF in
      patients experiencing pain, and will need to be confirmed using larger datasets.

PMID- 22398161
TI  - Ultraviolet B induces high mobility group box 1 release from mouse peritoneal
      macrophages in vitro via caspase-1 mediated secretion pathway.
AB  - High mobility group box 1 (HMGB1) protein is a unique non histone nuclear protein
      that acts extracellularly as a mediator of delayed inflammation. Sub lethal dose
      of UVB triggers the release of cytokines from macrophages (MPhis). Adding to the
      panoply of UVB induced cytokines; it is reported that UVB induces HMGB1 release
      from mouse peritoneal MPhis in time and partially dose dependent manner,
      independent of TNF-alpha. UVB also enhanced the transcription of HMGB1 gene and
      expression of cellular protein, which influences its subsequent release. HMGB1 is
      secreted by an unconventional secretion pathway of unknown mechanism. Caspase-1
      has been shown to function as a general regulator of stress induced
      unconventional secretion for a number of cytokines. In the present study, we have
      observed that pharmacological inhibitors specific for caspase-1 (ZVAD and YVAD)
      abrogated UVB induced HMGB1 release from MPhis. This effect was most likely
      mediated via physical interaction between HMGB1 and active caspase-1 (p10 and
      p20) as demonstrated by immunoprecipitation. In addition, it was found that HMGB1
      and active caspase-1 p20 release depends on UVB mediated enhancement of
      intracellular Ca(2+). Thus our data suggests that optimal dose of UVB (50
      mJ/cm(2)) induces HMGB1 upregulation and active release from mouse peritoneal
      MPhis which is mediated by caspase-1 in a Ca(2+) dependent manner.

PMID- 22398162
TI  - A hydrothermal seep on the Costa Rica margin: middle ground in a continuum of
      reducing ecosystems.
AB  - Upon their initial discovery, hydrothermal vents and methane seeps were
      considered to be related but distinct ecosystems, with different distributions,
      geomorphology, temperatures, geochemical properties and mostly different species.
      However, subsequently discovered vents and seep systems have blurred this
      distinction. Here, we report on a composite, hydrothermal seep ecosystem at a
      subducting seamount on the convergent Costa Rica margin that represents an
      intermediate between vent and seep ecosystems. Diffuse flow of shimmering, warm
      fluids with high methane concentrations supports a mixture of microbes, animal
      species, assemblages and trophic pathways with vent and seep affinities. Their
      coexistence reinforces the continuity of reducing environments and exemplifies a
      setting conducive to interactive evolution of vent and seep biota.

PMID- 22398163
TI  - Trade-offs shape the evolution of the vector-borne insect pathogen Xenorhabdus
      nematophila.
AB  - Our current understanding on how pathogens evolve relies on the hypothesis that
      pathogens' transmission is traded off against host exploitation. In this study,
      we surveyed the possibility that trade-offs determine the evolution of the
      bacterial insect pathogen, Xenorhabdus nematophila. This bacterium rapidly kills
      the hosts it infects and is transmitted from host cadavers to new insects by a
      nematode vector, Steinernema carpocapsae. In order to detect trade-offs in this
      biological system, we produced 20 bacterial lineages using an experimental
      evolution protocol. These lineages differ, among other things, in their virulence
      towards the insect host. We found that nematode parasitic success increases with
      bacteria virulence, but their survival during dispersal decreases with the number
      of bacteria they carry. Other bacterial traits, such as production of the
      haemolytic protein XaxAB, have a strong impact on nematode reproduction. We then
      combined the result of our measurements with an estimate of bacteria fitness,
      which was divided into a parasitic component and a dispersal component. Contrary
      to what was expected in the trade-off hypothesis, we found no significant
      negative correlation between the two components of bacteria fitness. Still, we
      found that bacteria fitness is maximized when nematodes carry an intermediate
      number of cells. Our results therefore demonstrate the existence of a trade-off
      in X. nematophila, which is caused, in part, by the reduction in survival this
      bacterium causes to its nematode vectors.

PMID- 22398164
TI  - Are personality differences in a small iteroparous mammal maintained by a life
      history trade-off?
AB  - Despite increasing interest, animal personality is still a puzzling phenomenon.
      Several theoretical models have been proposed to explain intraindividual
      consistency and interindividual variation in behaviour, which have been primarily
      supported by qualitative data and simulations. Using an empirical approach, I
      tested predictions of one main life-history hypothesis, which posits that
      consistent individual differences in behaviour are favoured by a trade-off
      between current and future reproduction. Data on life-history were collected for
      individuals of a natural population of grey mouse lemurs (Microcebus murinus).
      Using open-field and novel-object tests, I quantified variation in activity,
      exploration and boldness for 117 individuals over 3 years. I found systematic
      variation in boldness between individuals of different residual reproductive
      value. Young males with low current but high expected future fitness were less
      bold than older males with high current fecundity, and males might increase in
      boldness with age. Females have low variation in assets and in boldness with age.
      Body condition was not related to boldness and only explained marginal variation
      in exploration. Overall, these data indicate that a trade-off between current and
      future reproduction might maintain personality variation in mouse lemurs, and
      thus provide empirical support of this life-history trade-off hypothesis.

PMID- 22398165
TI  - Close kinship within multiple-genotype malaria parasite infections.
AB  - Malaria infections containing multiple parasite genotypes are ubiquitous in
      nature, and play a central role in models of recombination, intra-host dynamics,
      virulence, sex ratio, immunity and drug resistance evolution in Plasmodium. While
      these multiple infections (MIs) are often assumed to result from superinfection
      (bites from multiple infected mosquitoes), we know remarkably little about their
      composition or generation. We isolated 336 parasite clones from eight patients
      from Malawi (high transmission) and six from Thailand (low transmission) by
      dilution cloning. These were genotyped using 384 single-nucleotide polymorphisms,
      revealing 22 independent haplotypes in Malawi (2-6 per MI) and 15 in Thailand (2
      5 per MI). Surprisingly, all six patients from Thailand and six of eight from
      Malawi contained related haplotypes, and haplotypes were more similar within-
      than between-infections. These results argue against a simple superinfection
      model. Instead, the observed kinship patterns may be explained by inoculation of
      multiple related haploid sporozoites from single mosquito bites, by immune
      suppression of parasite subpopulations within infections, and serial transmission
      of related parasites between people. That relatedness is maintained in endemic
      areas in the face of repeated bites from infected mosquitoes has profound
      implications for understanding malaria transmission, immunity and intra-host
      dynamics of co-infecting parasite genotypes.

PMID- 22398166
TI  - Consequences of fisheries-induced evolution for population productivity and
      recovery potential.
AB  - Fisheries-induced evolution has become a major branch of the research on
      anthropogenic and contemporary evolution. Within the conservation context,
      fisheries-induced evolution has been hypothesized to negatively affect the
      persistence and recovery potential of depleted populations, but this has not been
      explicitly investigated. Here, we investigate how fisheries-induced evolution of
      Atlantic cod (Gadus morhua L.) life histories affects per capita population
      growth rate, a parameter negatively correlated with extinction risk. We simulate
      the evolutionary and ecological dynamics of a cod population for a 100 year
      period of size-selective harvesting, followed thereafter by 300 years of
      recovery. To evaluate the relative importance of harvest-induced evolution, we
      either allowed life histories to evolve during and after the fishing period, or
      we assumed that fisheries-induced evolution was absent. Population growth rates
      did not differ appreciably between the evolutionary and non-evolutionary
      simulation scenarios, despite the emergence of rather pronounced differences in
      life histories. The underlying reason was that in the absence of fishing the
      cumulative lifetime reproductive outputs were very similar among differing life
      histories. The results suggest that fisheries-induced evolution might not always
      have as clear-cut an effect on population growth rate as previously anticipated.

PMID- 22398167
TI  - Water deprivation induces appetite and alters metabolic strategy in Notomys
      alexis: unique mechanisms for water production in the desert.
AB  - Like many desert animals, the spinifex hopping mouse, Notomys alexis, can
      maintain water balance without drinking water. The role of the kidney in
      producing a small volume of highly concentrated urine has been well-documented,
      but little is known about the physiological mechanisms underpinning the metabolic
      production of water to offset obligatory water loss. In Notomys, we found that
      water deprivation (WD) induced a sustained high food intake that exceeded the pre
      deprivation level, which was driven by parallel changes in plasma leptin and
      ghrelin and the expression of orexigenic and anorectic neuropeptide genes in the
      hypothalamus; these changed in a direction that would stimulate appetite. As the
      period of WD was prolonged, body fat disappeared but body mass increased
      gradually, which was attributed to hepatic glycogen storage. Switching metabolic
      strategy from lipids to carbohydrates would enhance metabolic water production
      per oxygen molecule, thus providing a mechanism to minimize respiratory water
      loss. The changes observed in appetite control and metabolic strategy in Notomys
      were absent or less prominent in laboratory mice. This study reveals novel
      mechanisms for appetite regulation and energy metabolism that could be essential
      for desert rodents to survive in xeric environments.

PMID- 22398168
TI  - Not an ancient relic: the endemic Livistona palms of arid central Australia could
      have been introduced by humans.
AB  - Livistona mariae is an endemic palm localized in arid central Australia. This
      species is separated by about 1000 km from its congener L. rigida, which grows
      distantly in the Roper River and Nicholson-Gregory River catchments in northern
      Australia. Such an isolated distribution of L. mariae has been assumed to have
      resulted from contraction of ancestral populations as Australia aridified from
      the Mid-Miocene (ca 15 Ma). To test this hypothesis at the population level, we
      examined the genetic relationships among 14 populations of L. mariae and L.
      rigida using eight nuclear microsatellite loci. Our population tree and Bayesian
      clustering revealed that these populations comprised two genetically distinct
      groups that did not correspond to the current classification at species rank, and
      L. mariae showed closest affinity with L. rigida from Roper River. Furthermore,
      coalescent divergence-time estimations suggested that the disjunction between the
      northern populations (within L. rigida) could have originated by intermittent
      colonization along an ancient river that has been drowned repeatedly by marine
      transgression. During that time, L. mariae populations could have been
      established by opportunistic immigrants from Roper River about 15 000 years ago,
      concurrently with the settlement of indigenous Australians in central Australia,
      who are thus plausible vectors. Thus, our results rule out the ancient relic
      hypothesis for the origin of L. mariae.

PMID- 22398169
TI  - Brood care and social evolution in termites.
AB  - Cooperative brood care is assumed to be the common driving factor leading to
      sociality. While this seems to be true for social Hymenoptera and many
      cooperatively breeding vertebrates, the importance of brood care for the
      evolution of eusociality in termites is unclear. A first step in elucidating this
      problem is an assessment of the ancestral condition in termites. We investigated
      this by determining the overall level of brood care behaviour across four termite
      species that cover the phylogenetic diversity of the lower termites. Brood care
      was low in the three species (all from different families) that had an ancestral
      wood-dwelling lifestyle of living in a single piece of wood that serves as food
      and shelter. In the fourth species, a lower termite that evolved outside
      foraging, brood care was more common. Together with data for higher termites,
      this suggests that brood care in termites only becomes important when switching
      from a wood-dwelling to a foraging lifestyle. These results imply that early
      social evolution in termites was driven by benefits of increased defence, while
      eusociality in Hymenoptera and cooperative breeding in birds and mammals are
      primarily based on brood care.

PMID- 22398171
TI  - O' mother where wert thou? Maternal strategies in the southern elephant seal: a
      stable isotope investigation.
AB  - Maternal effects are widespread in ecology and can alter the dynamics of a
      population. We investigated the impact of maternal foraging strategies on
      offspring weaning mass--a proxy of maternal foraging success and of offspring
      survival--in southern elephant seals on iles Kerguelen. Using 4 years of data, we
      modelled pup weaning mass as a two-component mixture and used blood stable
      isotope values to discriminate between maternal foraging strategies previously
      identified from bio-logging studies. Carbon isotope ratio was a strong predictor
      of weaning mass, but the relationship was non-monotonic in contrast to a priori
      expectations. Females foraging in the interfrontal zone weaned pups with a
      smaller mass compared with females foraging in Antarctic waters. Pup mass was
      positively correlated with a proxy of global primary production in the
      interfrontal zone for small weanlings. Maternal effects, via a poor foraging
      efficiency in the 1970s, may help explain the large population decrease observed
      at that time on iles Kerguelen because of an overall decrease in pup weaning
      mass, survival and subsequent recruitment.

PMID- 22398170
TI  - Modelling seasonal variations in the age and incidence of Kawasaki disease to
      explore possible infectious aetiologies.
AB  - The average age of infection is expected to vary during seasonal epidemics in a
      way that is predictable from the epidemiological features, such as the duration
      of infectiousness and the nature of population mixing. However, it is not known
      whether such changes can be detected and verified using routinely collected data.
      We examined the correlation between the weekly number and average age of cases
      using data on pre-vaccination measles and rotavirus. We show that age-incidence
      patterns can be observed and predicted for these childhood infections.
      Incorporating additional information about important features of the transmission
      dynamics improves the correspondence between model predictions and empirical
      data. We then explored whether knowledge of the age-incidence pattern can shed
      light on the epidemiological features of diseases of unknown aetiology, such as
      Kawasaki disease (KD). Our results indicate KD is unlikely to be triggered by a
      single acute immunizing infection, but is consistent with an infection of longer
      duration, a non-immunizing infection or co-infection with an acute agent and one
      with longer duration. Age-incidence patterns can lend insight into important
      epidemiological features of infections, providing information on transmission
      relevant population mixing for known infections and clues about the aetiology of
      complex paediatric diseases.

PMID- 22398172
TI  - Life history predicts risk of species decline in a stochastic world.
AB  - Understanding what traits determine the extinction risk of species has been a
      long-standing challenge. Natural populations increasingly experience reductions
      in habitat and population size concurrent with increasing novel environmental
      variation owing to anthropogenic disturbance and climate change. Recent studies
      show that a species risk of decline towards extinction is often non-random across
      species with different life histories. We propose that species with life
      histories in which all stage-specific vital rates are more evenly important to
      population growth rate may be less likely to decline towards extinction under
      these pressures. To test our prediction, we modelled declines in population
      growth rates under simulated stochastic disturbance to the vital rates of 105
      species taken from the literature. Populations with more equally important vital
      rates, determined using elasticity analysis, declined more slowly across a
      gradient of increasing simulated environmental variation. Furthermore, higher
      evenness of elasticity was significantly correlated with a reduced chance of
      listing as Threatened on the International Union for Conservation of Nature Red
      List. The relative importance of life-history traits of diverse species can help
      us infer how natural assemblages will be affected by novel anthropogenic and
      climatic disturbances.

PMID- 22398173
TI  - Keep things simple for safer childbirth and better medicine.

PMID- 22398174
TI  - Active management of the third stage of labour with and without controlled cord
      traction: a randomised, controlled, non-inferiority trial.
AB  - BACKGROUND: Active management of the third stage of labour reduces the risk of
      post-partum haemorrhage. We aimed to assess whether controlled cord traction can
      be omitted from active management of this stage without increasing the risk of
      severe haemorrhage. METHODS: We did a multicentre, non-inferiority, randomised
      controlled trial in 16 hospitals and two primary health-care centres in
      Argentina, Egypt, India, Kenya, the Philippines, South Africa, Thailand, and
      Uganda. Women expecting to deliver singleton babies vaginally (ie, not planned
      caesarean section) were randomly assigned (in a 1:1 ratio) with a centrally
      generated allocation sequence, stratified by country, to placental delivery with
      gravity and maternal effort (simplified package) or controlled cord traction
      applied immediately after uterine contraction and cord clamping (full package).
      After randomisation, allocation could not be concealed from investigators,
      participants, or assessors. Oxytocin 10 IU was administered immediately after
      birth with cord clamping after 1-3 min. Uterine massage was done after placental
      delivery according to local policy. The primary (non-inferiority) outcome was
      blood loss of 1000 mL or more (severe haemorrhage). The non-inferiority margin
      for the risk ratio was 1.3. Analysis was by modified intention-to-treat,
      excluding women who had emergency caesarean sections. This trial is registered
      with the Australian and New Zealand Clinical Trials Registry, ACTRN
      12608000434392. FINDINGS: Between June 1, 2009, and Oct 30, 2010, 12,227 women
      were randomly assigned to the simplified package group and 12,163 to the full
      package group. After exclusion of women who had emergency caesarean sections,
      11,861 were in the simplified package group and 11,820 were in the full package
      group. The primary outcome of blood loss of 1000 mL or more had a risk ratio of
      1.09 (95% CI 0.91-1.31) and the upper 95% CI limit crossed the pre-stated non
      inferiority margin. One case of uterine inversion occurred in the full package
      group. Other adverse events were haemorrhage-related. INTERPRETATION: Although
      the hypothesis of non-inferiority was not met, omission of controlled cord
      traction has very little effect on the risk of severe haemorrhage. Scaling up of
      haemorrhage prevention programmes for non-hospital settings can safely focus on
      use of oxytocin. FUNDING: United States Agency for International Development and
      UN Development Programme/UN Population Fund/WHO/World Bank Special Programme of
      Research, Development and Research Training in Human Reproduction, Department of
      Reproductive Health and Research.

PMID- 22398175
TI  - Knee replacement.
AB  - Knee-replacement surgery is frequently done and highly successful. It relieves
      pain and improves knee function in people with advanced arthritis of the joint.
      The most common indication for the procedure is osteoarthritis. We review the
      epidemiology of and risk factors for knee replacement. Because replacement is
      increasingly considered for patients younger than 55 years, improved decision
      making about whether a patient should undergo the procedure is needed. We discuss
      assessment of surgery outcomes based on data for revision surgery from national
      joint-replacement registries and on patient-reported outcome measures. Widespread
      surveillance of existing implants is urgently needed alongside the carefully
      monitored introduction of new implant designs. Developments for the future are
      improved delivery of care and training for surgeons and clinical teams. In an
      increasingly ageing society, the demand for knee-replacement surgery will
      probably rise further, and we predict future trends. We also emphasise the need
      for new strategies to treat early-stage osteoarthritis, which will ultimately
      reduce the demand for joint-replacement surgery.

PMID- 22398176
TI  - X-linked sideroblastic anemia and ataxia: a new family with identification of a
      fourth ABCB7 gene mutation.
AB  - X-linked sideroblastic anemia and ataxia (XLSA-A) is a rare cause of early onset
      ataxia, which may be overlooked due to the usually mild asymptomatic anemia. The
      genetic defect has been identified as a mutation in the ABCB7 gene at Xq12-q13.
      The gene encodes a mitochondrial ATP-binding cassette (ABC) transporter protein
      involved in iron homeostasis. Until now only three families have been reported,
      each with a distinct missense mutation in this gene. We describe a fourth family
      with XLSA-A and a novel mutation in the ABCB7 gene.

PMID- 22398177
TI  - Antiepileptic drug withdrawal in childhood epilepsy: what are the risk factors
      associated with seizure relapse?
AB  - BACKGROUND: In recent years, several studies have been conducted to determine the
      risk of relapse after antiepileptic drug (AED) withdrawal: there is no general
      agreement on criteria that can predict safe discontinuation or seizure
      recurrence. AIMS: To evaluate prospectively the relapse rate of epilepsy
      associated to AED withdrawal in epileptic children and to determine the risk
      factors of seizure recurrence. METHODS: One hundred-sixty-eight children with
      epilepsy who were seizure-free for at least 2 years were enrolled and all
      children were proposed to stop AED treatment and were followed. In all children
      electroencephalograms (EEGs) were performed before the withdrawal of AEDs and
      after discontinuation of the treatment. RESULTS: A total of 48 (28.6%) children
      relapsed; half of these patients relapsed while reducing the AED dose and the
      other half after the AED was withdrawn; after 2 years without AEDs, the risk of
      relapse was very low. Data evaluated by multivariable analysis showed that the
      children receiving polytherapy before AED withdrawal, having a history of febrile
      seizures and suffering from multiple seizure types relapsed more frequently. The
      presence of abnormal post-withdrawal EEG recordings was associated with a higher
      risk of seizure recurrence. CONCLUSIONS: Epileptic children, after a seizure-free
      period of 2 years, have a low risk of seizure recurrence. The potential risk
      factors of relapse, are multiple seizure types previous polytherapy, history of
      febrile seizures and abnormalities in post-withdrawal EEG.

PMID- 22398178
TI  - Alcohol drinking and risk of renal cell carcinoma: results of a meta-analysis.
AB  - BACKGROUND: The role of alcohol consumption in relation with renal cell carcinoma
      is still unclear; a few studies have reported a beneficial effect of moderate
      levels of alcohol consumption, whereas it remains still under debate whether
      there is a dose-response association. MATERIALS AND METHODS: Twenty observational
      studies (4 cohort, 1 pooled and 15 case-control) reporting results on at least
      three levels of alcohol consumption were selected through a combined search with
      PubMed and EMBASE of articles published before November 2010. Overall relative
      risks (RRs) and 95% confidence intervals (CIs) were estimated using random
      effects models, and both second-order fractional polynomials and random effect
      meta-regression models were implemented for the study of dose-risk relation.
      RESULTS: The estimated RRs were 0.85 (95% CI: 0.80-0.92) for any alcohol
      drinking, 0.90 (95% CI: 0.83-0.97) for light drinking (0.01-12.49 g/day), 0.79
      (95% CI: 0.71-0.88) for moderate drinking (12.5-49.9 g/day) and 0.89 (95% CI:
      0.58-1.39) for heavy drinking (>=50 g/day), respectively. CONCLUSION: Our meta
      analysis supports the hypothesis of a negative effect of moderate alcohol
      consumption on the risk of renal cell cancer.

PMID- 22398179
TI  - A general approach for high yield fabrication of CMOS-compatible all
      semiconducting carbon nanotube field effect transistors.
AB  - We report strategies to achieve both high assembly yield of carbon nanotubes at
      selected positions of the circuit via dielectrophoresis (DEP) and field effect
      transistor (FET) yield using an aqueous solution of semiconducting-enriched
      single-walled carbon nanotubes (s-SWNTs). When the DEP parameters were optimized
      for the assembly of individual s-SWNTs, 97% of the devices showed FET behavior
      with a maximum mobility of 210 cm2 V(-1) s(-1), on-off current ratio ~10(6) and
      on-conductance up to 3 uS, but with an assembly yield of only 33%. As the DEP
      parameters were optimized so that one to five s-SWNTs are connected per electrode
      pair, the assembly yield was almost 90%, with ~90% of these assembled devices
      demonstrating FET behavior. Further optimization gave an assembly yield of 100%
      with up to 10 SWNTs per site, but with a reduced FET yield of 59%. Improved FET
      performance including higher current on-off ratio and high switching speed were
      obtained by integrating a local Al2O3 gate to the device. Our 90% FET with 90%
      assembly yield is the highest reported so far for carbon nanotube devices. Our
      study provides a pathway which could become a general approach for the high yield
      fabrication of complementary metal oxide semiconductor (CMOS)-compatible carbon
      nanotube FETs.

PMID- 22398180
TI  - How schema and novelty augment memory formation.
AB  - Information that is congruent with existing knowledge (a schema) is usually
      better remembered than less congruent information. Only recently, however, has
      the role of schemas in memory been studied from a systems neuroscience
      perspective. Moreover, incongruent (novel) information is also sometimes better
      remembered. Here, we review lesion and neuroimaging findings in animals and
      humans that relate to this apparent paradoxical relationship between schema and
      novelty. In addition, we sketch a framework relating key brain regions in medial
      temporal lobe (MTL) and medial prefrontal cortex (mPFC) during encoding,
      consolidation and retrieval of information as a function of its congruency with
      existing information represented in neocortex. An important aspect of this
      framework is the efficiency of learning enabled by congruency-dependent MTL-mPFC
      interactions.

PMID- 22398181
TI  - Overview of the study design, participation and field work of the German
      Environmental Survey on Children 2003-2006 (GerES IV).
AB  - The German Federal Environment Agency carried out its fourth German Environmental
      Survey (GerES IV), which is the first survey on children only and the environment
      related module of the German Health Interview and Examination Survey for Children
      and Adolescents (German acronym: KiGGS), conducted by the Robert Koch Institute
      (RKI). The German Environmental Surveys are nationwide population studies
      conducted to determine the exposure to environmental pollutants, to explore
      exposure pathways and to identify sub-groups with higher exposure. GerES IV was
      conducted on randomly selected 1790 children aged 3-14 years from the cross
      sectional sample of KiGGS. The participants of GerES IV lived in 150 sampling
      locations all over Germany. Field work was carried out from May 2003 to May 2006.
      The response rate in GerES IV was 77.3%. Due to the fact that participation in
      GerES IV was limited to children that had previously participated in the KiGGS
      study, the total response rate in GerES IV resulted in 52.6%. Response rates did
      neither differ significantly between West and East Germany, nor between different
      community sizes, age groups and gender. The basic study programme included blood
      samples, morning urine, tap water and house dust as well as comprehensive
      questionnaire-based interviews. In addition, subgroups were studied with regard
      to "noise, hearing capacity and stress hormones", "chemical contamination of
      indoor air" and "biogenic indoor contamination". A key element of the field work
      in GerES IV was a home visit to carry out interviews, conduct measurements and
      collect samples. An exception was blood sampling which was carried out within
      KiGGS. The quality of field work, data collection, evaluation, and chemical,
      biological and physical analyses was successfully evaluated by internal and
      external quality assurance. This comprehensive overview aims at giving other
      research groups the opportunity to compare different study designs or to adapt
      their own design to get comparable results.

PMID- 22398182
TI  - Sarcoidosis presenting as a lytic lesion of the mandible.

PMID- 22398183
TI  - Risk factors for third molar occlusal caries: a longitudinal clinical
      investigation.
AB  - PURPOSE: To study the third molar occlusal caries incidence and identify related
      patient-level sociodemographic, dental behavior, and clinical risk factors.
      PATIENTS AND METHODS: A prospective cohort study was used to study caries risk
      (crude increment and incidence rate) on retained and erupted to the occlusal
      plane third molars among a moderate-size (n = 215) group of healthy (American
      Society of Anesthesiologists class I and II) young adults (median age, 26 years)
      followed up for a mean of 4.6 years. Clinical data were gathered by calibrated
      examiners using visual-tactile and radiographic diagnostic methods on all molar
      teeth. The covariates included age at enrollment, gender, race, income,
      education, frequency of dental visits, oral hygiene behaviors, and smoking.
      Summary statistics and visual methods were used for data description. The
      analyses relied on bivariate and multivariate methods using generalized
      estimating equations, extensions of Poisson modeling. RESULTS: Of the 215
      patients, 33% developed occlusal caries on 1 or more retained third molars. The
      incidence rate was 0.11 (95% confidence interval 0.09 to 0.13) third molar
      "increments"/person-year. Those with any molar caries at baseline were 80% more
      likely to have a new third molar caries lesion at the end of follow-up compared
      with those with caries-free molars (prevalence ratio, 1.80; 95% confidence
      interval, 1.08 to 3.00). The third molar caries rate was halved for every
      approximately 9 years of the subjects' baseline age. Favorable oral hygiene
      behaviors and better socioeconomic status were associated with decreased caries
      risk. However, independent of other covariates, smoking increased the third molar
      caries risk twofold. CONCLUSIONS: Younger patients from lower socioeconomic
      strata, smokers, and those with poor oral hygiene behavior are at an increased
      risk of occlusal caries development on their retained third molars.

PMID- 22398184
TI  - A rare case of osteonecrosis in the premaxilla following meningococcal-induced
      disseminated intravascular coagulation.

PMID- 22398185
TI  - Ultrasonography for detection of disc displacement of temporomandibular joint: a
      systematic review and meta-analysis.
AB  - PURPOSE: To assess the diagnostic efficacy of ultrasonography in detecting disc
      displacement of the temporomandibular joint. MATERIALS AND METHODS: MEDLINE
      (using OVID, 1950 to April 2011), EMBASE (1980 to April 2011), and the Chinese
      Biomedical Literature Database (1978 to April 2011) were searched electronically.
      In addition, relevant journals and reference lists of the included studies were
      manually searched for any eligible studies on diagnostic accuracy. Two authors
      performed the study inclusion, data extraction, and risk of bias assessment in
      duplicate. Meta-analysis was performed with MetaDisc 1.4. RESULTS: Fifteen
      studies were included in this meta-analysis; 6 studies had a low risk of bias, 6
      studies an unclear risk, and 3 studies a high risk. Meta-regression indicated
      that the detected results were not influenced by the types of ultrasonography,
      image dimensions, types of transducer, and ultrasonic image of the disc (P >
      .05). The Q* values of ultrasonography for the closed- and open-mouth positions
      were 0.79 and 0.91, respectively. The diagnostic efficacy of disc displacement
      with reduction had a sensitivity of 0.76, a specificity of 0.82, a positive
      likelihood ratio of 3.80, a negative likelihood ratio of 0.36, a diagnostic odds
      ratio of 10.95, an area under the curve of 0.83, and a Q* of 0.76. The diagnostic
      efficacy of disc displacement without reduction had a sensitivity of 0.79, a
      specificity of 0.91, a positive likelihood ratio of 80.5, a negative likelihood
      ratio of 0.25, diagnostic odds ratio of 36.80, an area under the curve of 0.97,
      and a Q* of 0.92. CONCLUSIONS: The diagnostic efficacy of ultrasonography is
      acceptable and can be used as a rapid preliminary diagnostic method to exclude
      some clinical suspicions. However, positive ultrasonographic findings should be
      confirmed by magnetic resonance imaging. Also, the ability of ultrasonography to
      detect lateral and posterior displacements is still unclear. More high-quality
      studies are needed to assess the diagnostic efficacies of some specific
      ultrasonographic methods. Standards and criteria for ultrasonographic techniques
      in the diagnosis of disc displacement should be established in the future.

PMID- 22398186
TI  - Is adjuvant laser therapy effective for preventing pain, swelling, and trismus
      after surgical removal of impacted mandibular third molars? A systematic review
      and meta-analysis.
AB  - PURPOSE: To assess the efficacy and safety of low-level laser energy irradiation
      (LLEI) for decreasing pain, swelling, and trismus after surgical removal of
      impacted mandibular third molars (IMTMs). MATERIALS AND METHODS: MEDLINE, EMBASE,
      and the Central Register of Controlled Trials of the Cochrane Library were
      searched from their inception, and conference proceedings, cross-references, and
      gray literature were searched for the last 5 years for randomized and quasi
      randomized controlled trials that evaluated the effects of any type of LLEI,
      compared with active or inactive treatments, in patients undergoing surgical
      removal of IMTMs. Risk of bias in included studies was assessed by 2 independent
      evaluators using the Cochrane Risk of Bias tool. A random-effects model meta
      analysis was used to estimate the mean difference of trismus between the groups.
      Heterogeneity was assessed using Cochran chi(2) and I(2). RESULTS: Ten eligible
      trials were included in this systematic review. The included studies overall had
      a moderate risk of bias. Because of heterogeneity in the intervention and
      outcomes assessments, pain and swelling outcomes were only qualitatively
      summarized and indicated no beneficial effects of LLEI over placebo. Patients
      receiving LLEI had an average of 4.2 mm (95% confidence interval, 1.2 to 7.2) and
      5.2 mm (95% confidence interval, 1.8 to 8.2) less trismus than patients receiving
      no active treatment on the second and seventh day after the surgery,
      respectively. CONCLUSIONS: There was no benefit of LLEI on pain or swelling and a
      moderate benefit on trismus after removal of IMTMs. It is necessary to
      standardize the intervention and outcomes assessment and to conduct adequately
      powered, well-designed trials to evaluate the efficacy of LLEI.

PMID- 22398187
TI  - Seed, soil and secreted hormones: potential interactions of breast cancer cells
      with their endocrine/paracrine microenvironment and implications for treatment
      with bisphosphonates.
AB  - The process of formation of metastasis is undoubtedly inefficient, with the
      majority of disseminated tumour cells perishing in their metastatic environment.
      Their ability to survive is determined by their intrinsic abilities, with
      emerging evidence of the importance of cancer stem cells possessing self
      propagating potential, but also the interaction with the premetastatic niche,
      which may either help or hinder their formation into micrometastasis, thus
      influencing recurrence and survival in breast cancer patients. Use of the bone
      targeted agents bisphosphonates in the adjuvant setting has been extensively
      studied in large clinical trials, and demonstrated an interesting interplay with
      the endocrine microenvironment, with postmenopausal women or premenopausal women
      receiving ovarian suppression therapy gaining a survival advantage compared to
      pre/perimenopausal women. The interaction between the endocrine hormones and the
      paracrine TGFbeta growth factors may provide an explanation for the differences
      seen according to ovarian function in the response to bisphosphonates. In this
      review the evidence of interplay between ovarian endocrine hormones, TGFbeta
      paracrine growth factors and bisphosphonates will be presented, and subsequent
      influence on breast cancer cells in the bone pre-metastatic niche hypothesised.

PMID- 22398188
TI  - Central nervous system tuberculoma.
AB  - The aim of this study was to outline the clinicoradiological features of central
      nervous system (CNS) tuberculoma, and highlight the importance of early
      treatment. We conducted a retrospective analysis between 1999 and 2008.
      Clinicoradiological, pathological and follow-up data of 23 patients were reviewed
      and analysed. The mean age at presentation was 30.3 years (range=17-43 years),
      and the average disease duration at presentation was six months (range=1-19
      months). The tuberculoma location in the cohort was: thoracic region (10
      patients); cervical region (six), cervicothoracic region (three); thoracolumbar
      region (one); and intracranial (six); three patients (13%) had multiple lesions.
      Nineteen (82.6%) and 15 (65.2%) patients had sensory-motor and bowel/bladder
      involvement, respectively. Two patients presented with headache and consciousness
      disturbance, and two patients had a history of pulmonary Koch's disease. Five
      patients had a history of tuberculous meningoencephalitis, and one patient had a
      history of enlarged cervical lymph nodes. Twenty-one patients underwent surgery,
      and two received conservative treatment; all patients received anti-tuberculosis
      therapy for 18 months. Seventeen of the 21 surgical patients and both
      conservatively managed patients achieved improved neurological function (with
      Karnofsky Performance Scale scores of 90-100). Patients presenting at an advanced
      disease stage had a poorer outcome. CNS tuberculoma is a benign condition with a
      good prognosis and effective therapy options. Enhanced brain and spine MRI should
      be performed to ensure the diagnosis is not missed. Early surgical decompression
      is recommended for intramedullary tuberculoma. Craniotomy is indicated for
      patients with intracranial hypertension, while more conservative therapy is
      appropriate for patients who have intracranial tuberculomas without intracranial
      hypertension.

PMID- 22398189
TI  - Severe necrosis of oesophageal and gastric mucosa in fatal methanol poisoning.
AB  - Methanol is a potent neurotoxic substance that causes severe metabolic acidosis
      and serious neurological disorders. Most of the cases are accidental exposures to
      drinking beverages contaminated with methanol. There are few articles reporting
      pure methanol intoxication; however, it is well known that small quantities of
      pure methanol causes blindness and death, the minimum lethal dose being 50-100
      ml.A case report is presented of a 67-year-old woman, who committed suicide by
      ingestion of 500 ml of absolute methanol. Despite symptomatic and supportive
      intensive care, the woman died 23 h after hospital admission due to metabolic
      acidosis and multiple organ dysfunction syndrome. A complete medico-legal autopsy
      was performed. Grossly, there was complete detachment of the oesophagus mucosa
      and brownish discolouration of the gastric mucosa. Histological findings showed
      diffuse haemorrhagic necrosis of the stomach mucosa and intense acute
      inflammatory infiltration of the lamina propria. To our knowledge, this is the
      first autopsy report of such severe digestive injuries. A discussion and review
      of the recent literature on the subject are given.

PMID- 22398190
TI  - Decentralised CD38 activation monitoring: aspects of practical implementation and
      standardisation.
AB  - BACKGROUND: In light of the HIV pandemic, significant strides have been made in
      improving treatment options for patients. Technologies to monitor the progress of
      a patient on such treatment have therefore also been scaled up. Immune activation
      as measured by CD38 mean fluorescence intensity (MFI) on CD8 T cells has been
      successfully shown in a clinical trial to predict response to antiretroviral
      therapy (ART) and reported as a cost effective real time test to supplement more
      costly VL testing. In this study we report transfer of this technology from the
      research into the routine environment. METHODS: This study was conducted in 2
      parts: Firstly, fresh random samples (n=75) were tested at four time intervals
      (0, 24, 36 and 48 h) post-venesection to review reproducibility of CD38 MFI
      expression. Secondly, the CD38 MFI assay was introduced into a pilot regional
      testing facility and random samples (n=40) were validated against values obtained
      on matched samples tested at the reference laboratory. RESULTS: The CD38 assay
      showed acceptable accuracy and reproducibility up to 36 h (98% similarity) after
      venesection with some reduction in CD38 MFI to 94% at 48 h (bias<0.2MFI, %CV<5).
      Implementation at the secondary testing site was successful with 98% similarity
      (% SIM CV<5%) compared to the reference laboratory. CONCLUSION: The assay proved
      stable over time and could be tested until 48 h after venesection with no loss of
      CD38 MFI. Off-site implementation also proved successful, as such, the CD38 assay
      offers a reliable real time supplementary test to long-term VL monitoring of HIV
      infected patients on the national ART programme.

PMID- 22398191
TI  - [Modelization of bone graft reconstruction for posterior mandibular segment using
      the Simplant(r) software].
AB  - INTRODUCTION: Pre-implant reconstruction techniques of edentulous molar
      mandibular ridges take into account the height and the width of the initial
      ridge, but not the initial geometry. The Simplant((r)) software allows modeling
      these techniques by taking into account this geometry. TECHNICAL NOTE: Four
      surgical techniques for crestal volume reconstruction (apposition, interposition,
      distraction, formwork) were used on seven hemi-mandibles and modeled with the
      Simplant((r)) software. This reconstructed volume was visualized according to the
      initial crestal geometry. The average gain in height was 4.1mm for the onlay
      graft, 2.3mm for the interposition graft, 4mm for distraction, 5.1mm for the
      boxing. The average gain of crestal width was -0.3mm for the onlay graft, 1mm for
      the interposition, -0.5mm for the distraction, and 1.3mm for the boxing.
      DISCUSSION: Modeling with the Simplant((r)) software shows that boxing technique
      gives the closest bone reconstruction to the ideal crestal geometry, whatever the
      initial crestal geometry.

PMID- 22398192
TI  - [A gingival tumor of the mandible].

PMID- 22398193
TI  - [Interventional multidimodal hybrid unit: from pre-operative planning to
      immediate post-operative control].
AB  - INTRODUCTION: Computer assisted surgery has rapidly developed over the last
      decade, essentially due to the development of navigation and 3D virtual surgical
      planning and image fusion technologies. The recent introduction of intra
      operative cone-beam CT scan (CBCT), which integrates flat panel technology,
      allows for high resolution bone imaging, the quality and accuracy of which is
      similar to the one obtained by conventional spiral CT scan. The combination of
      these two technologies in a "hybrid" operating unit enables the convergence of
      the pre-, intra- and post-operative steps in a linear computer-assisted
      processing chain, which optimises surgery accuracy, predictability and patient
      outcomes while potentially reducing costs, operating times and need for further
      surgical revision. TECHNICAL NOTE: The "hybrid" unit includes: 1) the operating
      room (65 m(2)) equipped with horizontal laminar-flow, a mobile monoplane ceiling
      suspended C-arm CBCT scan system with a flat panel detector, a wireless
      navigation system, and an interactive wall-mount touch screen 2) the control room
      (18 m(2)) separated from the operating room by an X-ray lead protective glass
      window, including two separate computer workstations for 3D image integration and
      processing 3) the scrub room (17 m(2)) with two separate stainless steel surgical
      wash-basins. The intra-operative protocol includes the following steps: 1)
      elaboration of the patient specific pre-operative computed planning and
      simulation based on pre-operatively and/or intra-operatively acquired patient
      images 2) intra-operative navigational guidance setting 3) surgical procedure 4)
      intra-operative 3D CT imaging 5) suture.

PMID- 22398194
TI  - Sesamol alleviates diet-induced cardiometabolic syndrome in rats via up
      regulating PPARgamma, PPARalpha and e-NOS.
AB  - Increased oxidative stress and inflammation in obesity are the central and causal
      components in the pathogenesis and progression of cardiometabolic syndrome
      (CMetS). The aim of the study was to determine the potential role of sesamol (a
      natural powerful antioxidant and anti-inflammatory phenol derivative of sesame
      oil) in chronic high-cholesterol/high-fat diet (HFD)-induced CMetS in rats and to
      explore the molecular mechanism driving this activity. Rats were fed with HFD
      (55% calorie from fat and 2% cholesterol) for 60 days to induce obesity,
      dyslipidemia, insulin resistance (IR), hepatic steatosis and hypertension. On the
      30th day, rats with total cholesterol >150 mg/dl were considered
      hypercholesterolemic and administered sesamol 2, 4 and 8 mg/kg per day for the
      next 30 days. Sesamol treatment decreased IR, hyperinsulinemia, hyperglycemia,
      dyslipidemia, TNF-alpha, IL-6, leptin, resistin, highly sensitive C-reactive
      protein (hs-CRP), hepatic transaminases and alkaline phosphatase, along with
      normalization of adiponectin, nitric oxide and arterial pressures in a dose
      dependent fashion. Increased TBARS, nitrotyrosine and decreased antioxidant
      enzyme activities were also amended in HFD rats. Similarly, sesamol normalized
      hepatic steatosis and ultrastructural pathological alteration in hepatocytes,
      although the effect was more pronounced at 8 mg/kg. Furthermore, hepatic
      PPARgamma, PPARalpha and e-NOS protein expressions were increased, whereas
      LXRalpha, SERBP-1c, P-JNK and NF-kappaB expression were decreased by sesamol
      treatment. These results suggest that sesamol attenuates oxidative stress,
      inflammation, IR, hepatic steatosis and hypertension in HFD-fed rats via
      modulating PPARgamma, NF-kappaB, P-JNK, PPARalpha, LXRalpha, SREBP-1c and e-NOS
      protein expressions, thereby preventing CMetS. Thus, the present study
      demonstrates the therapeutic potential of sesamol in alleviating CMetS.

PMID- 22398196
TI  - Monte Carlo calculations of positron emitter yields in proton radiotherapy.
AB  - Positron emission tomography (PET) is a promising tool for monitoring the three
      dimensional dose distribution in charged particle radiotherapy. PET imaging
      during or shortly after proton treatment is based on the detection of
      annihilation photons following the beta(+)-decay of radionuclides resulting from
      nuclear reactions in the irradiated tissue. Therapy monitoring is achieved by
      comparing the measured spatial distribution of irradiation-induced beta(+)
      activity with the predicted distribution based on the treatment plan. The
      accuracy of the calculated distribution depends on the correctness of the
      computational models, implemented in the employed Monte Carlo (MC) codes that
      describe the interactions of the charged particle beam with matter and the
      production of radionuclides and secondary particles. However, no well-established
      theoretical models exist for predicting the nuclear interactions and so
      phenomenological models are typically used based on parameters derived from
      experimental data. Unfortunately, the experimental data presently available are
      insufficient to validate such phenomenological hadronic interaction models.
      Hence, a comparison among the models used by the different MC packages is
      desirable. In this work, starting from a common geometry, we compare the
      performances of MCNPX, GATE and PHITS MC codes in predicting the amount and
      spatial distribution of proton-induced activity, at therapeutic energies, to the
      already experimentally validated PET modelling based on the FLUKA MC code. In
      particular, we show how the amount of beta(+)-emitters produced in tissue-like
      media depends on the physics model and cross-sectional data used to describe the
      proton nuclear interactions, thus calling for future experimental campaigns
      aiming at supporting improvements of MC modelling for clinical application of PET
      monitoring.

PMID- 22398197
TI  - In vitro evaluation of bisnaphthalimidopropyl derivatives loaded into pegylated
      nanoparticles against Leishmania infantum protozoa.
AB  - Bisnaphthalimidopropyl (BNIP) derivatives have recently been shown to have
      potential as antileishmanial agents. However, these compounds have some
      drawbacks, including their low aqueous solubility and some toxic effects. In this
      study, we designed a drug delivery system for enhanced delivery of BNIP
      derivative compounds whilst reducing adverse toxic effects, and hence increasing
      their biological efficacy. A coated drug delivery system based on polymeric
      nanoparticles of pegylated poly(lactic acid) (PLA), a biodegradable polymer, was
      successfully achieved. The pegylated PLA nanoformulations loaded with BNIP
      derivatives were evaluated in an in vitro model of intracellular amastigotes in
      murine J774 and human THP-1 cells for visceral leishmaniasis using luciferase
      expressing Leishmania infantum parasites. Pegylation of PLA nanoparticles
      significantly reduced the capacity of empty nanoparticles in inhibiting
      intracellular parasite growth. The BNIP derivatives BNIPDadec and BNIPDaoct
      exhibited EC(50) values (concentration of compound necessary to decrease cell
      viability to 50% of the untreated control) of ca. 4.5 MUM for THP-1 and J774
      cells and ca. 9.0 MUM for mouse bone marrow-derived macrophages. Nanoparticle
      encapsulation of the BNIP derivative compounds decreased their toxicity towards
      macrophages by >=10-fold as evaluated by the MTT assay. The antileishmanial
      activity of free BNIPDadec was 1.02+/-0.41 MUM and 0.73+/-0.06 MUM for THP-1 and
      J774 macrophages, respectively. Pegylation of PLA nanoparticles loaded with
      BNIPDadec resulted in EC(50) values of 1.43+/-0.63 MUM and 1.79+/-0.77 MUM for
      THP-1 and J774 macrophages, respectively. A similar trend was observed for free
      BNIPDaoct and pegylated BNIPDaoct PLA nanoparticles (2.43+/-0.19 MUM and 1.23+/
      0.40 MUM for THP-1 macrophages and 1.36+/-0.17 MUM and 1.52+/-0.57 MUM for J774
      macrophages). The nanoformulations were more efficient in reducing parasitic
      growth inside human macrophages than in murine cells, suggesting host cell
      dependent metabolism.

PMID- 22398195
TI  - Endocrine disruptors and asthma-associated chemicals in consumer products.
AB  - BACKGROUND: Laboratory and human studies raise concerns about endocrine
      disruption and asthma resulting from exposure to chemicals in consumer products.
      Limited labeling or testing information is available to evaluate products as
      exposure sources. OBJECTIVES: We analytically quantified endocrine disruptors and
      asthma-related chemicals in a range of cosmetics, personal care products,
      cleaners, sunscreens, and vinyl products. We also evaluated whether product
      labels provide information that can be used to select products without these
      chemicals. METHODS: We selected 213 commercial products representing 50 product
      types. We tested 42 composited samples of high-market-share products, and we
      tested 43 alternative products identified using criteria expected to minimize
      target compounds. Analytes included parabens, phthalates, bisphenol A (BPA),
      triclosan, ethanolamines, alkylphenols, fragrances, glycol ethers,
      cyclosiloxanes, and ultraviolet (UV) filters. RESULTS: We detected 55 compounds,
      indicating a wide range of exposures from common products. Vinyl products
      contained > 10% bis(2-ethylhexyl) phthalate (DEHP) and could be an important
      source of DEHP in homes. In other products, the highest concentrations and
      numbers of detects were in the fragranced products (e.g., perfume, air
      fresheners, and dryer sheets) and in sunscreens. Some products that did not
      contain the well-known endocrine-disrupting phthalates contained other less
      studied phthalates (dicyclohexyl phthalate, diisononyl phthalate, and di-n-propyl
      phthalate; also endocrine-disrupting compounds), suggesting a substitution. Many
      detected chemicals were not listed on product labels. CONCLUSIONS: Common
      products contain complex mixtures of EDCs and asthma-related compounds.
      Toxicological studies of these mixtures are needed to understand their biological
      activity. Regarding epidemiology, our findings raise concern about potential
      confounding from co-occurring chemicals and misclassification due to variability
      in product composition. Consumers should be able to avoid some target chemicals
      synthetic fragrances, BPA, and regulated active ingredients-using purchasing
      criteria. More complete product labeling would enable consumers to avoid the rest
      of the target chemicals.

PMID- 22398198
TI  - Treatment failure and recurrence of Clostridium difficile infection following
      treatment with vancomycin or metronidazole: a systematic review of the evidence.
AB  - The objective of this review was to evaluate the frequency of treatment failure
      and recurrence of Clostridium difficile infection (CDI) following treatment with
      vancomycin or metronidazole in recently performed studies (last 10 years).
      Searches in PubMed and Scopus were performed by two reviewers independently. Data
      regarding treatment failure and recurrence following metronidazole and vancomycin
      treatment were extracted and analysed. In total, 39 articles (7005 patients) were
      selected for inclusion in the systematic review. The reported treatment failure
      was 22.4% with metronidazole (16 studies) and 14.2% with vancomycin (8 studies).
      Recurrence of CDI occurred in 27.1% of patients following metronidazole treatment
      (18 studies) and 24.0% of patients following vancomycin treatment (8 studies).
      Mean treatment failure and recurrence in the selected studies was 22.3% (24
      studies) and 22.1% (37 studies). The reported outcomes depended on the study
      design (higher in prospective and retrospective cohort studies than in randomised
      controlled trials), geographic location of the study (higher in North America
      than in Europe and Asia), funding (higher in studies funded by non-profit
      organisations than pharmaceutical companies), mean age of the studied population
      (higher in older patients) and duration of follow-up (higher in studies with
      follow-up >1 month). In conclusion, infection with C. difficile is associated
      with 22.4% and 14.2% treatment failure and 27.1% and 24.0% recurrence after
      treatment with metronidazole and vancomycin, respectively. The variation in the
      reported outcomes amongst studies depends on the study design, location, funding,
      age and follow-up period.

PMID- 22398199
TI  - Wide phenotypic spectrum of the TARDBP gene: homozygosity of A382T mutation in a
      patient presenting with amyotrophic lateral sclerosis, Parkinson's disease, and
      frontotemporal lobar degeneration, and in neurologically healthy subject.
AB  - Mutations in the TARDBP gene are described as a cause of autosomal dominant
      amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD)
      with or without motor neuron involvement, and, recently, Parkinson's disease
      (PD). We hereby describe a family presenting the A382T mutation; two subjects
      were in the homozygous state, and two were in the heterozygous state. The index
      case, carrying the A382T mutation in the homozygous state, had an 8-year history
      of sporadic PD and 6 years later developed ALS and FTLD; his brother, carrying
      the same mutation in the homozygous state, and the other two family member
      carriers of the same mutation in the heterozygous state were without neurological
      signs and symptoms. This family confirms that mutation in transactive response
      (TAR)-DNA-binding protein 43 (TDP43), both the homozygous and the heterozygous
      state, may be found in subjects with different clinical conditions ranging from
      neurological disease to non-neurological disease. In addition, the aforementioned
      findings add to the debate for the ethical and psychological dilemmas about
      genetic counseling.

PMID- 22398200
TI  - Stenting across head and neck vessels using covered stents for persisting aortic
      arch obstruction.
AB  - OBJECTIVE: To describe endovascular stent placement using partially covered
      stents to preserve flow in head and neck vessels. BACKGROUND: Endovascular stent
      placement has become established as a first-line therapy for native coarctation
      of the aorta or re-coarctation in older children and adults. Increasingly covered
      stents are becoming the preferred option over bare-metal stents because of the
      perceived lower risk of aneurysm formation. Open-cell bare-metal stents are
      chosen when there is a high likelihood of jailing a head and neck vessel. Here we
      describe partial uncovering of a covered stent before implantation to allow flow
      through the uncovered portion of the stent to the branch vessel but preserve the
      covering over the majority of the remaining stent. METHODS: We describe two cases
      with aortic arch hypoplasia and re-coarctation, both of which required two
      partially uncovered stents for a satisfactory result. CONCLUSIONS: Endovascular
      stent placement is becoming the preferred option in the management of coarctation
      of the aorta in older children and adults. Strategies to deal with transverse
      arch hypoplasia and multiple levels of aortic arch obstruction frequently
      involving branch vessels or aneurysms need to be considered before these
      procedures are embarked upon. Partially uncovering stents may afford more
      protection than using bare-metal stents in the transverse and distal arch while
      preserving flow in head and neck branches, and is a technically straightforward
      procedure.

PMID- 22398201
TI  - Complications following robot-assisted radical prostatectomy in a prospective
      Canadian cohort of 305 consecutive cases.
AB  - BACKGROUND: Robot-assisted radical prostatectomy (RARP) has emerged in the last
      decade as an alternative to open radical prostatectomy for men with localized
      prostate cancer. The increased cost of this technique has been justified by its
      ability to reduce blood loss, and to provide improved vision, less postoperative
      pain and more rapid recovery from surgery, while maintaining satisfactory
      oncological and functional outcomes. Given the increasing diffusion of robotic
      surgical technology within Canada and its associated high capital and operating
      costs, we review the clinical outcomes and complications from 305 consecutive
      cases performed at our Canadian institution. METHODS: A consecutive cohort of 305
      patients with a mean follow-up of 30 months was analyzed with institutional
      ethics approval. All patients were treated and reviewed postoperatively by a
      single surgeon (SP). The primary aim of the study was to assess the incidence and
      type of complications associated with RARP in a Canadian setting. Our prospective
      database captured preoperative, intra-operative and postoperative data and was
      maintained by an individual independent of the robotic program. We report
      complications categorized according to the Clavien system. Multiple complications
      seen in an individual were recorded separately for the purposes of our analysis.
      RESULTS: Between April 2005 and October 2010, 305 patients underwent RARP at our
      institution. A total of 70 complications were identified, with 47 (67.1%)
      requiring only conservative or pharmacological management (Clavien I-II). Twenty
      three patients were found to have a major complication (Clavien III-V). Of the 16
      who required intervention under general anesthesia, 3 required emergency
      treatment and the remaining patients underwent elective surgery. CONCLUSIONS:
      RARP has been incorporated at our institution with an acceptably low rate of
      intra-operative and postoperative complications. We have found that the database
      was effective in providing patients with outcome-related information, which in
      turn helped us gain patient consent with regard to the institution-specific risks
      of RARP.

PMID- 22398202
TI  - A comparison of the metabolic profiles of diabetic and non-diabetic uric acid
      stone formers.
AB  - INTRODUCTION: The aim of this study was to compare the metabolic profiles of
      diabetic and non-diabetic patients with uric acid stones to understand whether
      preventive strategies should be tailored to reflect different causative factors.
      METHODS: The results of the metabolic evaluation of patients with uric acid
      stones identified prospectively from the Metabolic Stone Clinic at St. Joseph's
      Hospital, London, Canada were reviewed. Information included patients' clinical
      histories, 24 hour urine collections, blood chemistry and stone analysis.
      RESULTS: Complete data were obtained from 68 patients with uric acid stones.
      Twenty-two patients had diabetes. There were no statistically significant
      differences in mean age, body mass index, or history of gout. Among diabetics,
      pure uric acid stones were identified in 14 patients (63%) and mixed uric acid in
      8 (36%). Pure uric acid stones were more common in the diabetic cohort (63% vs.
      46%, p = 0.16). Urine pH, serum and urine uric acid levels and 24-hour urine
      volumes were similar in both groups. The diabetic group had an increased average
      oxalate excretion (424 MUmol/d vs. 324 MUmol/d, p = 0.003). CONCLUSION: The exact
      etiological basis for the higher oxalate excretion in diabetic uric acid stone
      formers is unclear. Whether this is a metabolic feature of diabetes, due to
      dietary indiscretion or the iatrogenic consequence of dietary advice requires
      further investigation.

PMID- 22398203
TI  - Alteration of renal cyclooxygenase expression due to partial unilateral ureteral
      obstruction in neonatal.
AB  - INTRODUCTION: Impaired renal water handling in response to neonatally-induced
      partial unilateral ureteral obstruction (PUUO) may be associated with altered
      expression of cyclooxygenase (COX). The purpose of the present study was to
      examine whether long-term PUUO induced at birth was associated with changes of
      COX-2. METHODS: Rats were subjected to PUUO (n = 14) or a sham operation (n = 12)
      within the first 48 hours of life. The rats were divided into 4 groups: (1) PUUO
      at 9 weeks (n = 7); (2) the sham operation at 9 weeks (n = 6); (3) PUUO at 15
      weeks (n = 7); and (4) the sham operation at 15 weeks (n = 6). Urine and blood
      samples were collected before sacrificing the animals. Plasma potassium,
      creatinine and urea, as well as the osmolality and sodium of plasma and urine
      were tested in each sample. The expression of renal COX-1 and COX-2 was examined
      at 9 and 15 weeks in rats with neonatally-induced PUUO within the first 48 hours
      of life by immunoblotting and immunocytochemistry. RESULTS: PUUO caused a marked
      decrease in urine osmolality and a significant increase in urinary sodium of the
      obstructed kidney compared with the sham-operated kidney at 9 and 15 weeks.
      Immunoblotting analysis showed that an abundance of COX-2 in the obstructed
      kidney significantly increased compared with the non-obstructed kidney and sham
      operated kidney at 9 weeks (p < 0.05) and 15 weeks (p < 0.05) in rats with PUUO.
      In contrast, COX-1 abundance in the obstructed kidney was similar to that in the
      non-obstructed kidney. Immunocytochemistry confirmed these findings. CONCLUSION:
      Renal COX-2 expression in the obstructed kidney is significantly altered in
      response to neonatally-induced PUUO. A marked increase in COX-2 indicates that it
      may be an important factor in reducing renal handling of sodium and water in
      response to PUUO.

PMID- 22398204
TI  - How reliable is 12-core prostate biopsy procedure in the detection of prostate
      cancer?
AB  - INTRODUCTION: Prostate biopsies incur the risk of being false-negative and this
      risk has not yet been evaluated for 12-core prostate biopsy. We calculated the
      false-negative rate of 12-core prostate biopsy and determined the patient
      characteristics which might affect detection rate. METHODS: We included 90
      prostate cancer patients (mean age of 64, range: 49-77) diagnosed with
      transrectal ultrasound guided 12-core prostate biopsy between December 2005 and
      April 2008. All patients underwent radical retropubic prostatectomy and the 12
      core prostate biopsy procedure was repeated on surgical specimen ex-vivo. Results
      of preoperative and postoperative prostate biopsies were compared. We analyzed
      the influence of patient age, prostate weight, serum prostate-specific antigen
      (PSA) level, free/total PSA ratio, PSA density and Gleason score on detection
      rate. RESULTS: In 67.8% of patients, prostate cancer was detected with repeated
      ex-vivo biopsies using the same mapping postoperatively. We found an increase in
      PSA level, PSA density and biopsy Gleason score; patient age, decreases in
      prostate weight and free/total PSA ratio yielded higher detection rates. All
      cores, except the left-lateral cores, showed mild-moderate or moderate internal
      consistency. Preoperative in-vivo biopsy Gleason scores remained the same,
      decreased and increased in 43.3%, 8.9% and 47.8% of patients, respectively, on
      final specimen pathology. CONCLUSIONS: The detection rate of prostate cancer with
      12-core biopsy in patients (all of whom had prostate cancer) was considerably
      low. Effectively, repeat biopsies can still be negative despite the patient's
      reality of having prostate cancer. The detection rate is higher if 12-core
      biopsies are repeated in younger patients, patients with high PSA levels, PSA
      density and Gleason scores, in addition in patients with smaller prostates, lower
      free/total PSA ratios.

PMID- 22398205
TI  - A review of glycosylated carriers for drug delivery.
AB  - Carbohydrates not only represent a vast potential as structure building blocks of
      living cells but also have proved as a promising candidate for drug delivery.
      Glycosylation of nanocarriers instructs some gratifying characteristic, which
      leads to the evolution of promising delivery systems. Some path-breaking
      advantages of glycosylated carriers include the engineered release profile of
      bioactives when introduced into biological system. Being natural product of
      living system these carriers also upshots as a multifaceted drug delivery vehicle
      and reduces the toxicity associated with unmodified drug carrier and therapeutic
      agent. An additional attribute of these carriers is to alter the pharmacokinetic
      profile of drugs positively with stabilization of drug carrier. The presence of
      lectin receptors on different cell surfaces makes the glycosylated carrier
      appreciable for targeted delivery of drugs to improve their therapeutic index.
      Active participation of some lectin receptors in immune responses to antigen
      overlaid the application of glycosylated carriers in delivery of antigen and
      immunotherapy for treatment of ailments like cancer. These advantages revealed
      the promising potential of glycosylated carriers in each perspective of drug
      delivery. Collectively this review presents an overview of different applications
      of glycosylated carriers, with a focus on their applicability in development of a
      nanoconstruct with GRAS status.

PMID- 22398206
TI  - Use of macrophages to deliver therapeutic and imaging contrast agents to tumors.
AB  - Drug targeting to tumors with limited toxicity and enhanced efficacy of drug is
      one of the important goals for cancer treatment pharmaceutics.
      Monocytes/macrophages are able to migrate to tumor sites across the blood
      barriers by acting as Trojan horses carrying drug cargoes. Taking this advantage,
      we have intended to develop an efficient administration system using a
      biologically active carrier of mouse peritoneal macrophage bearing liposomal
      doxorubicin (macrophage-LP-Dox). We expect that this system could improve the
      cancer therapeutic efficacy through deeper penetration into tumor even hypoxic
      region behind tumor blood vessel. We first confirmed that macrophages containing
      iron oxides could migrate and infiltrate into tumors effectively by MR imaging.
      Next, we showed that doxorubicin (Dox) encapsulated with liposomes (LP-Dox) was
      successfully loaded into macrophages, in which the biological activity of
      macrophage and cytotoxicity of Dox against tumor cells were well preserved.
      Delivery of Dox into tumor tissue by systemic administration of macrophage-LP-Dox
      was verified in both subcutaneous and metastasis xenograft tumor models.
      Importantly, the effective inhibition of in vivo tumor growth was proved with
      this system. Our results provide the feasibility of macrophages-LP-drug as an
      active biocarrier for the enhancement of therapeutic effects in cancer treatment
      and open new perspectives for the active delivery of drugs.

PMID- 22398207
TI  - Alternative oxidase rescues mitochondria-mediated dopaminergic cell loss in
      Drosophila.
AB  - Mitochondrial dysfunction is commonly observed in degenerative disorders,
      including Alzheimer's and Parkinson's disease that are characterized by the
      progressive and selective loss of neuronal subpopulations. It is currently
      unclear, however, whether mitochondrial dysfunction is primary or secondary to
      other pathogenic processes that eventually lead to age-related neurodegeneration.
      Here we establish an in vivo Drosophila model of mitochondrial dysfunction by
      downregulating the catalytic subunit of mitochondrial DNA (mtDNA) polymerase in
      cholinergic, serotonergic and dopaminergic neurons. The resulting flies are
      characterized by lowered respiratory chain activity, premature aging, age-related
      motor deficits as well as adult onset, progressive and cell-type-specific,
      dopaminergic neurodegeneration. Using this model, we find that associated
      lethality can be partially rescued by targeting PINK1/parkin signaling or Drp1,
      both of which have been implicated in mitochondrial dynamics and Parkinson's
      disease. Bypassing mitochondrial complex III/IV deficiencies with Alternative
      oxidase (AOX), however, fully restores ATP levels and prevents dopaminergic
      neurodegeneration. In contrast, ATP levels and neurodegeneration are not rescued
      when mitochondrial complex I deficiencies are bypassed with NADH-Q
      oxidoreductase. Our results demonstrate that mtDNA-mediated mitochondrial
      dysfunction can cause age-related and cell-type-specific neurodegeneration which
      AOX is able to alleviate and indicate that AOX or its surrogates may prove useful
      as a therapeutic tool for limiting respiratory chain deficiencies caused by mtDNA
      decline in healthy aging and neurodegenerative disease.

PMID- 22398209
TI  - Design principles of interconnections between chromatin and pre-mRNA splicing.
AB  - In human cell nuclei, the vast majority of mRNA precursors (pre-mRNA) are spliced
      in more than one way. The process of alternative splicing creates enormous
      biological complexity from a limited number of genes, and its misregulation often
      leads to disease. Splicing regulation relies primarily on RNA-binding proteins
      that recognize specific target features in the pre-mRNA. Evidence accumulated
      over the past decade has further shown that most splicing occurs co
      transcriptionally and that transcription modulates splicing. More recently,
      chromatin emerged as a novel node in the network of splicing regulatory
      interactions. Chromatin structure influences splicing choices but splicing can
      also actively modulate the pattern of histone modification in chromatin. This
      review discusses how splicing, transcription and chromatin are interwoven bi
      directionally.

PMID- 22398208
TI  - Genetic ablation of Pals1 in retinal progenitor cells models the retinal
      pathology of Leber congenital amaurosis.
AB  - Mutation of the polarity gene Crumbs homolog 1 (CRB1) is responsible for >10% of
      Leber congenital amaurosis (LCA) cases worldwide; LCA is characterized by early
      onset degenerative retinal dystrophy. The role of CRB1 in LCA8 pathogenesis
      remains elusive since Crb1 mouse mutants, including a null allele, have failed to
      mimic the early-onset of LCA, most likely due to functional compensation by
      closely related genes encoding Crb2 and Crb3. Crb proteins form an evolutionarily
      conserved, apical polarity complex with the scaffolding protein associated with
      lin-seven 1 (Pals1), also known as MAGUK p55 subfamily member 5 (MPP5). Pals1 and
      Crbs are functionally inter-dependent in establishing and maintaining epithelial
      polarity. Pals1 is a single gene in the mouse and human genomes; therefore, we
      ablated Pals1 to establish a mouse genetic model mimicking human LCA. In our
      study, the deletion of Pals1 leads to the disruption of the apical localization
      of Crb proteins in retinal progenitors and the adult retina, validating their
      mutual interaction. Remarkably, the Pals1 mutant mouse exhibits the critical
      features of LCA such as early visual impairment as assessed by electroretinogram,
      disorganization of lamination and apical junctions and retinal degeneration. Our
      data uncover the indispensible role of Pals1 in retinal development, likely
      involving the maintenance of retinal polarity and survival of retinal neurons,
      thus providing the basis for the pathologic mechanisms of LCA8.

PMID- 22398210
TI  - Fabrication and optical characterization of light trapping silicon nanopore and
      nanoscrew devices.
AB  - We have fabricated nanotextured Si substrates that exhibit controllable optical
      reflection intensities and colors. Si nanopore has a photon trapping
      nanostructure but has abrupt changes in the index of refraction displaying a
      darkened specular reflection. Nanoscrew Si shows graded refractive-index photon
      trapping structures that enable diffuse reflection to be as low as 2.2% over the
      visible wavelengths. By tuning the 3D nanoscale silicon structure, the optical
      reflection peak wavelength and intensity are changed in the wavelength range of
      300-800 nm, making the surface have different reflectivity and apparent colors.
      The relation between the surface optical properties with the spatial features of
      the photon trapping nanostructures is examined. Integration of photon trapping
      structures with planar Si structure on the same substrate is also demonstrated.
      The tunable photon trapping silicon structures have potential applications in
      enhancing the performance of semiconductor photoelectric devices.

PMID- 22398211
TI  - Directly suspended droplet microextraction coupled with high performance liquid
      chromatography: a rapid and sensitive method for acetaldehyde assay in peritoneal
      dialysis fluids.
AB  - The aim of present study was to develop and validate a rapid, sensitive,
      inexpensive and reliable method for the detection of trace levels of acetaldehyde
      in peritoneal dialysis fluids (PDFs) by 2,4-dinitrophenylhydrazine (DNPH)
      derivatization and extraction. Separation and analysis of acetaldehyde via 2,4
      dinitrophenylhydrazone (DNPH) was by reverse phase high performance liquid
      chromatography (HPLC). In order to remove co-eluting interferences and to pre
      concentrate acetaldehyde, the extraction and clean-up of the sample has been
      performed using a liquid phase microextraction technique. In this research
      directly suspended droplet microextraction technique (DSDME) coupled with HPLC
      was used to determine acetaldehyde in PDFs. In DSDME method a free suspended
      droplet of an organic solvent (1-octanol) used as extraction phase. Important
      factors such as organic solvent, extraction time, droplet volume, sample and
      reagent solution volumes and rate of stirring were optimized. After extraction
      under optimal conditions the samples were analyzed by HPLC with UV detection at
      360 nm. The linearity ranged from 0.01 to 100 mg L-1 with a relative standard
      deviation (RSD%; n=3) 5.6 Enrichment factor and limit of detection (LOD; n=5)
      were 54 and 1.12 MUg L-1, respectively.

PMID- 22398212
TI  - Detection of allantoin in clinical samples using hydrophilic liquid
      chromatography with stable isotope dilution negative ion tandem mass
      spectrometry.
AB  - Allantoin is the major oxidation product of urate in humans and is a potential
      biomarker of oxidative stress. Several methods are used to measure allantoin in
      biological samples but they have inherent issues that can include lack of
      specificity and sensitivity, difficulty in sample preparation, or artefactual
      generation of allantoin. We have developed a method for measuring allantoin using
      hydrophilic liquid chromatography with stable isotope dilution tandem mass
      spectrometry (HILIC-MS/MS). It was validated for measuring allantoin in plasma,
      synovial fluid and urine from human subjects. The limit of quantification was
      determined to be 10 fmol and the assay displayed excellent linearity for the wide
      range of concentrations found in clinical samples. Relative standard deviations
      were <5% for between-day and <7% for within-day variation. Accuracy was between
      100% and 104%. Concentrations of allantoin in plasma of healthy controls (2.0
      MUM; interquartile range 1.4-3.6 MUM, n=35) was significantly lower (p<0.001)
      than that in plasma from patients with rheumatoid arthritis (3.7 MUM; IQR 3.0-5.6
      MUM, n=43) and in synovial fluid of patients with gout (3.3 MUM; IQR 2.8-5.8 MUM,
      n=10). This newer HILIC-MS/MS method is a simple and highly sensitive assay for
      detection of allantoin. It can be used to assess the level of oxidative stress in
      human pathologies.

PMID- 22398213
TI  - Internal scatter, the unavoidable major component of the peripheral dose in
      photon-beam radiotherapy.
AB  - In clinical photon beams, the dose outside the geometrical field limits is
      produced by photons originating from (i) head leakage, (ii) scattering at the
      beam collimators and the flattening filter (head scatter) and (iii) scattering
      from the directly irradiated region of the patient or phantom (internal scatter).
      While the first two components can be modified, e.g. by reinforcement of
      shielding components or by re-modeling the filter system, internal scatter
      remains an unavoidable contributor to the peripheral dose. Its relative magnitude
      compared to the other components, its numerical variation with beam energy, field
      size and off-axis distance as well as its spectral distribution are evaluated in
      this study. We applied a detailed Monte Carlo (MC) model of our 6/15 MV Siemens
      Primus linear accelerator beam head, provided with ideal head leakage shielding
      conditions (multi-leaf collimator without gaps) to assess the head scatter
      contribution. Experimental values obtained under real shielding conditions were
      used to evaluate the head leakage contribution. It was found that the MC-computed
      internal scatter doses agree with the results of our previous measurements, that
      internal scatter is the major contributor to the peripheral dose in the near
      periphery while head leakage prevails in the far periphery, and that the lateral
      decline of the internal scatter dose can be represented by the sum of two
      exponentials, with an asymptotic tenth value of 18 to 19 cm. Internal scatter
      peripheral doses from various elementary beams are additive, so that their sum
      increases approximately in proportion with field size. The ratio between
      normalized internal scatter doses at 6 and 15 MV is approximately 2:1. The energy
      fluence spectra of the internal scatter component at all points of interest
      outside the field have peaks near 500 keV. The fact that the energy-shifted
      internal scatter constitutes the major contributor to the dose in the near
      periphery has a general bearing for dosimetry, i.e. for energy-dependent detector
      responses and dose conversion factors, for the relative biological effectiveness
      and for second primary malignancy risk estimates in the peripheral region.

PMID- 22398214
TI  - Influence of training years on upper-body strength and power changes during the
      competitive season for professional Australian rules football players.
AB  - OBJECTIVES: To determine if upper-body strength or power changes during the
      competitive season for elite Australian rules footballers and what influence the
      number of training years has on any changes. DESIGN: Repeated measures. METHODS:
      Twenty elite Australian rules footballers were assessed at preseason, in-season
      and postseason. Strength was assessed by the 1 Repetition Maximum bench press and
      power was assessed by bench press throws. Athletes' results were analysed as a
      whole group as well as being divided into two groups according to training years:
      less than 3 years training and greater than 3 years training. All athletes
      performed the same resistance training program. RESULTS: There were no
      significant differences in height, body mass, or skinfold measurements between
      the two age groups. As a whole group, there was no significant change in 1RM
      bench press. There was a small but significant decrease in mean bench throw power
      in-season (525 W) compared to preseason (542 W) and it then increased at
      postseason (541 W). Within group analysis revealed the in-season decrease in
      upper-body power was largely pertaining to the younger athletes. The older group
      maintained their upper body power levels while the younger group decreased power
      in-season (4%) before regaining it at season's end. CONCLUSION: Older footballers
      were able to maintain their upper body power while the younger footballers had a
      small but significant decrease in-season before regaining it by season's end. The
      overall volume of training and playing appears to have affected the younger
      athletes' power more than older athletes. Both age groups maintained upper body
      strength.

PMID- 22398216
TI  - Single institutional analysis of trends over 45 years in etiology of vocal fold
      paralysis.
AB  - OBJECTIVE: It is important to assess the causes of vocal fold paralysis. Many
      studies have reported causes of paralysis, but few reports have shown changes in
      longitudinal etiology in a single institution. METHODS: We investigated the
      medical records of 797 patients with vocal fold paralysis from 1990 to 2005 at
      the voice and bronchoesophageal outpatient clinics at the University of Tokyo
      Hospital. We evaluated the etiology of paralysis, and compared our results with a
      previous study by Hirose in our clinic from 1961 to 1989 to assess changes in
      etiology. RESULTS: The postoperative group comprised 466 patients (58.5%), while
      the non-surgical group comprised 331 (41.5%) patients. In the postoperative
      group, the most common cause of paralysis was thyroid surgery (106 cases), and
      other common causes were surgery for aortic aneurysm (61 cases) and tracheal
      intubation (58 cases). In the non-surgical group, idiopathic paralysis (134
      cases) was the most common cause. Other common causes were lung cancer (34 cases)
      and cerebrovascular disease (24 cases). In a previous study from our clinic, the
      rate of postoperative paralysis was 43.5%. In the current analysis, the
      percentage of postoperative patients has increased remarkably compared with that
      of the previous report while the rate of idiopathic paralysis, has decreased by
      half. CONCLUSION: The increase in postoperative cases of paralysis may be caused
      by the increasing frequency of operations for many diseases, due to the progress
      of medical techniques in recent years. The decrease in idiopathic cases may be
      related to the advances of diagnostic devices such as CT and MRI.

PMID- 22398215
TI  - Retrospective accounts of injection initiation in intimate partnerships.
AB  - BACKGROUND: The influence of family members, peers and sexual partners on
      initiation to injection drug use is well established. Furthermore, research on
      gender differences in injection initiation has recognized the increased
      vulnerability of women, in particular, to injection-related health risks, and the
      gendered nature of the injection initiation experience. Yet more research is
      needed on the interpersonal and structural dynamics that shape injection
      initiation within intimate partnerships. METHODS: This paper draws on narrative
      data from semi-structured ethnographic interviews with 25, relatively stable,
      drug-using couples from two New York City neighbourhoods. The study was conducted
      between 2007 and 2009. Our analyses focus on retrospective accounts of injection
      initiation from IDUs who were initiated to injection (or initiated their
      partners) in current or former intimate partnerships. In particular we analyse
      narratives of injection initiation events where both partners participated as
      initiates or initiators. RESULTS: Transition to injection within intimate
      partnerships was common, especially for women, and occurred in specific contexts.
      Structural and interpersonal dynamics, including the ubiquity of drugs in poor
      communities and the gendered nature of drug acquisition and use strategies, as
      well as the problem of increased drug tolerance, situational impediments to drug
      access, and the perceived cost-benefit of injecting, all influenced the process
      of initiation to injection drug use within couples. The data also suggest that,
      even when risks associated with injection initiation were understood, both
      pragmatic and emotional considerations within relationships tended to offset
      concerns about potential dangers. CONCLUSION: The findings suggest the need for a
      broad range of interventions (including couples-focussed interventions) to
      minimize rates of injection initiation within intimate partnerships.

PMID- 22398217
TI  - Recommendations for a definition of multiple sclerosis in support of early
      treatment.
AB  - The aim of the Multiple Sclerosis Think Tank (Groupe de Reflexion sur la Sclerose
      en Plaques: GRESEP), composed of hospital neurologists involved in the management
      of patients with multiple sclerosis, is to provide recommendations in response to
      clinical questions that are raised when managing these patients. After work done
      on the themes on useful serum testing with suspected multiple sclerosis, as well
      as the detection and management of cognitive disorders early in the course of the
      disease, the subject of the present work is the early definition and early
      treatment of the disease. Following a systematic literature review, a RAND/UCLA
      appropriateness-derived method enabled consensual recommendations among a working
      group, a rating group and a reading group to be developed and formulated. Each
      recommendation is presented with the degree of consensus that it was accorded.

PMID- 22398218
TI  - [Sleeping sickness: end of the epidemic outbreak?].
AB  - Sleeping sickness or human African trypanosomiasis is a parasitic disease
      transmitted by tsetse flies and therefore confined to its habitat, the central
      part of the African continent. Two disease forms are linked to two different
      parasites: T. b. gambiense and T. b. rhodesiense. Actual epidemiological data and
      precise and dynamic mapping of foci are in favor of a real decrease of the
      disease. Not all areas are under control and resurgence can still not be avoided
      from the remote areas where the disease is endemic. However, recent advances in
      knowledge in parasite genetics are giving hope of control. In 2009, for the first
      time since 50 years, less than 10,000 cases were declared to the World Health
      Organization. Clinical trials allowed revising some clinical concepts and linking
      them with parasite genetics: both disease forms can show variations from
      asymptomatic, chronic to acute and are linked to genetic differences in the host
      or the parasite. Parasitological diagnosis may be facilitated by the introduction
      of individual rapid tests and PCR-based field tests. Knowledge in mechanisms of
      brain invasion and screenings of inflammatory molecules allow new marker
      combinations for staging but they do not avoid lumbar puncture. Therapeutic
      options remain limited but there is hope to develop a new drug orally available
      in a near future.

PMID- 22398219
TI  - [Neuralgic amyotrophy as a manifestation of hepatitis E infection].

PMID- 22398220
TI  - Imatinib mesylate discontinuation in patients with chronic myeloid leukemia who
      have received front-line imatinib mesylate therapy and achieved complete
      molecular response.
AB  - The aims were to investigate the feasibility of imatinib mesylate (IM)
      discontinuation in chronic myeloid leukemia patients who were initially treated
      with IM and achieved complete molecular response (CMR). Fourteen patients were
      included. Ten were relapsed within 9.5 months after discontinuation of IM. All 7
      patients with high Sokal risk were relapsed. The probability of CMR persistence
      at 1-year was 28.6%. All relapsed patients were still responsive to IM. A high
      Sokal risk and delayed acquisition of CMR were associated with relapse. IM
      discontinuation in patients achieved CMR after treatment with front-line IM might
      be feasible. Further studies are warranted.

PMID- 22398221
TI  - Gli inhibitor GANT61 causes apoptosis in myeloid leukemia cells and acts in
      synergy with rapamycin.
AB  - Aberrant reactivation of Gli signaling has been described in a wide variety of
      human cancers and rapamycin can down-regulate Gli pathway in some solid tumors.
      In this study, we attempt to define the cytotoxic effect of Gli inhibitor on AML
      cells. And the regulation action of rapamycin on Gli in AML cells also has been
      assessed. Gli inhibitor GANT61 caused growth arrest and apoptosis in AML cells.
      Rapamycin decreased not only the Gli protein and mRNA expressions but also
      expression of the Gli-luciferase reporter in AML cells. Synergism effect between
      GANT61 and rapamycin was found in Kasumi-1, HL-60 and U937 cell lines. The
      results suggest that aberrant Gli activation is a feature of some myeloid
      leukemic cells and Gli activiation can be down-regulated by rapamycin.

PMID- 22398222
TI  - Trends in the use of topical over the counter products in the management of
      dermatologic disease in the United States.
AB  - BACKGROUND: Over the counter (OTC) products play an important role in treating
      and preventing disease in the U.S. Topical OTCs are widely used but use in
      dermatology is not well defined. OBJECTIVE: To characterize topical OTC use in
      the U.S. METHODS: The National Ambulatory Medical Care Survey was queried for
      physician visits in which topical OTCs were recorded. Physician specialty,
      patient demographics, and diagnoses were examined and linear regressions were
      performed to determine trends over time. RESULTS: From 1989 to 2008, there were
      an estimated 320 million visits documenting topical OTC recommendations; the
      majority of which were visits to a dermatologist (33.5%). Dermatologists most
      commonly recommended hydrocortisone (16.9%), benzoyl peroxide (13.3%), and
      sunscreen (7.4%). Dermatologists were more likely than other providers to use
      moisturizers in the treatment of dermatologic disease. Overall, topical OTC
      recommendations by all physicians has decreased over time (p < 0.0001). However,
      dermatologists' recommendations for moisturizers and sunscreens has increased
      significantly. CONCLUSION: Topical OTC products have an important role in the
      prevention and treatment of dermatologic disease. Topical OTC recommendations are
      decreasing over time whereas their use as complementary components
      (sunscreen/moisturizers) appears to be increasing. Increased awareness of the
      utility of these agents may help to improve patient outcomes.

PMID- 22398223
TI  - Practical use of biologic therapy in dermatology: some considerations and
      checklists.
AB  - BACKGROUND: Practice varies with respect to biologic therapy counseling and
      monitoring of biologic therapy. Because of the complexity, many physicians shy
      away from prescribing biologic therapy. OBJECTIVE: To create checklists and
      discuss considerations behind various counseling and monitoring issues. METHODS:
      The full prescribing information of infliximab, etanercept, adalimumab,
      golimumab, certolizumab, alefacept, ustekinumab, rituximab, and IVIg were
      reviewed in addition to National Psoriasis Foundation guidelines to create the
      checklists. RESULTS: Considerations of counseling for biologics includes
      explaining benefits, relative risks of not treating or alternative therapies,
      consequence of risk, preventability of risk, and likelihood of risk.
      Considerations regarding vaccination, viral hepatitis screening, tuberculosis
      screening, skin cancer screening, pregnancy, and anti-nuclear antibody screening
      are discussed. LIMITATIONS: Consensus is unavailable as to the extent of
      counseling or monitoring. This manuscript provides one perspective. CONCLUSIONS:
      This article reviews monitoring and patient counseling considerations for the use
      of biologics in dermatology. Tables for each drug are provided with checklists
      for counseling and monitoring.

PMID- 22398224
TI  - Alopecia: a review of laser and light therapies.
AB  - Since the 1980s, laser technology has become increasingly popular to treat a
      variety of cutaneous conditions. Its successful use as an epilator comes with the
      rare but interesting side effect of paradoxical hypertrichosis. In this review,
      we summarize cases describing hair growth after photoepilation, as well as
      studies testing laser and light sources as treatment for alopecia, particularly
      androgenetic alopecia and alopecia areata. We also discuss the possible biologic
      mechanisms by which phototherapy induces hair regeneration.

PMID- 22398225
TI  - Clinical spectrum of cutaneous leishmaniasis: an overview from Pakistan.
AB  - The clinical spectrum of leishmaniasis encompasses subclinical (inapparent),
      localized (skin lesions), and disseminated infection (cutaneous, mucosal, or
      visceral). The clinico-pathological picture of cutaneous leishmaniasis is
      variable and depends not only on the leishmania species but also on endemic
      region, host factors, and immuno-inflammatory responses. Symptomatic disease is
      subacute or chronic and diverse in presentation and outcome. Pakistan is one of
      the countries in which cutaneous leishmaniasis is becoming an epidemic disease
      and because of its morbidity and disfiguring scars, it is considered a serious
      public health problem. This is an attempt to review the clinical spectrum of old
      world cutaneous leishmaniasis, classical and unusual clinical presentations,
      occurring in Pakistan.

PMID- 22398226
TI  - Ectrodactyly, ectodermal dysplasia, and cleft lip-palate (EEC) syndrome without
      clefting: a rare case report.
AB  - Ectrodactyly, Ectodermal dysplasia, and Cleft lip-cleft palate (EEC) syndrome is
      a rare ectodermal dysplasia presenting with various combinations of its three
      components. It is an autosomal dominant disorder with variable expression and
      penetrance. Patients have features of ectodermal abnormalities and a split
      hand/foot deformity of the limbs. We report a case of this rare disorder in a 40
      year-old male who had ectrodactyly, ectodermal dysplasia, but no clefting of lips
      or palate.

PMID- 22398227
TI  - Multiple linear red bands on the fingernails: idiopathic polydactylous
      longitudinal erythronychia.
AB  - Longitudinal erythronychia refers to a linear red band that extends from the
      proximal nail fold or lunula to the distal tip of the nail. Multiple digits with
      one or more longitudinal red streaks, presenting in an individual without an
      associated skin condition, systemic disease, or subungual tumor, characterizes
      idiopathic polydactylous longitudinal erythronychia (IPLE). The nail findings in
      a woman with asymptomatic IPLE since childhood are described and the salient
      features of this condition in this individual and the 10 previously reported
      patients are summarized. IPLE is a nail dyschromia of undefined pathogenesis for
      which affected persons can be reassured of the benign nature of the condition and
      whose nails only require clinical monitoring.

PMID- 22398228
TI  - A palliative intervention allows discovery of a rare tumor: lymphoepithelioma
      like carcinoma of the skin.
AB  - An 85-year-old man is presented, suffering end-stage metastasizing hepatocellular
      carcinoma with a disabling tumor mass of 5 cm in diameter on his forehead. The
      tumor emitted an extremely foul odor, very disconcerting to the patient and
      family. The tumor was excised under local anaesthesia. Histopathologic
      examination disclosed the astonishing diagnosis of an extremely rare
      lymphoepithelioma-like carcinoma of the skin.

PMID- 22398229
TI  - Multiple facial cylindromas: a case report.
AB  - Cylindroma is a benign skin appendageal tumor arising from pluripotent stem cells
      in the folliculo-sebaceous-apocrine unit. Multiple cylindromas are usually seen
      as a component of Brooke-Spiegler syndrome (BSS) or as the only skin lesions of
      familial cylindromatosis (FC). The usual site of occurrence of such tumors is the
      scalp. We report a case of multiple cylindromas involving the face without any
      other feature of BSS and no family history supporting the possibility of FC.
      Multiple cylindromas of 7 years duration, confirmed by histopathological
      examination of multiple biopsies, were seen on the face of a 70-year-old woman.
      There was no history of similar lesions in any of her family members. Examination
      of the scalp revealed no lesions. Surgical excision of the larger lesions was
      performed to improve the facial appearance of the patient. This case is being
      reported for the unusual occurrence of multiple cylindromas only on the face
      without any features of BSS or FC.

PMID- 22398230
TI  - Persistent edematous-plaque photosensitivity observed with sitagliptin phosphate
      (Januvia(r)).
AB  - Photosensitivity to sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is
      reported. No previous reports of photosensitivity to any DPP-4 inhibitors are
      known. Physical examination of the patient revealed edematous plaques confined to
      sun-exposed areas of the skin. An unusual finding in this case was the spongy
      sensation upon palpation of the plaques. Histopathology revealed parakeratosis
      and abundant eosinophils, supporting the clinical impression of cutaneous drug
      sensitivity. The eruption finally cleared, approximately two years after onset.

PMID- 22398231
TI  - Successful treatment of eosinophilic pustular folliculitis with topical
      tacrolimus 0.1 percent ointment.
AB  - Classic eosinophilic pustular folliculitis (EPF), otherwise known as Ofugi
      disease, is a rare condition commonly treated with topical glucocorticosteroids.
      If this fails, oral indomethacin is frequently the next line. Because the
      condition is recurrent, the use of long term steroids may cause side effects such
      as skin atrophy, hypertrichosis, and dyspigmentation. Topical tacrolimus is an
      immunosuppressant that is generally used as a steroid-sparing agent in atopic
      dermatitis. We report a case of classic EPF, which was recurrent over 5 years
      that had failed topical glucocorticosteroids but was successfully treated with
      topical tacrolimus 0.1 percent ointment.

PMID- 22398232
TI  - Lichen planus pigmentosus-inversus: case report and review of an unusual entity.
AB  - Lichen planus pigmentosus-inversus is a rare variant of lichen planus, with less
      than 20 cases reported in the medical literature. It presents as asymptomatic to
      mildly pruritic, hyperpigmented macules and/or patches involving intertriginous
      and flexural areas and skin folds in light-skinned individuals. The unique
      pattern of skin involvement, clinical features, and histology are distinctive.
      The combination of hyperpigmented lesion(s) isolated to non-sun exposed,
      intertriginous, and flexural areas with lichenoid histology is unique and
      separates it from other similar entities, such as lichen planus actinus and
      erythema dyschromicum perstans/ashy dermatosis. The case well highlights this
      unusual condition and represents the first case reported in the United States.

PMID- 22398233
TI  - Letter: Primary cutaneous marginal zone B cell lymphoma of the face: a
      challenging diagnosis.
AB  - The primary cutaneous marginal zone B cell lymphoma is a small B cell lymphoma,
      including cells of the marginal zone, lymphoplasmacytic cells, and plasma cells.
      Clinically it manifests as erythematous or erythematous-violaceous papules,
      plaques, or nodules, single or multiple, most often located to the extremities.
      Its course is usually indolent, with a survival at 5 years of approximately 97
      percent. The tumor exhibits a tendency towards local recurrence, but spread to
      locations outside the skin is extremely rare. We present a case report of a man,
      80 years of age, with a primary cutaneous marginal B cell lymphoma of the chin,
      an atypical location.

PMID- 22398234
TI  - Letter: Allergic contact dermatitis from sculptured acrylic nails: special
      presentation with a possible airborne pattern.
AB  - INTRODUCTION: Sculptured artificial acrylic nails are widely used in developed
      countries. Methylmethacrylate was first reported in 1941 as a cause of allergic
      contact dermatitis. Since then, occupational contact allergies to acrylates in
      dentistry, orthopedic surgery, printing industry and other industries have been
      reported. OBJECTIVE: We describe 3 patients with contact allergy to acrylates in
      artificial nails. DESIGN AND METHODS: Patch tests with the Portuguese baseline
      series of contact allergens and an extended series of acrylates was applied.
      RESULTS: We observed three female patients with allergic contact dermatitis from
      sculptured acrylic nails. Two of these patients were both customers and also
      technical nail beauticians. Two patients developed periungual eczema; one patient
      presented only with eyelid dermatitis and no hand or periungual lesions. The
      tests showed positive reactions to 2-hydroxyethylmethacrylate (2-HEMA) and 2
      hydroxypropylmethacrylate (2-HPMA) in three patients. CONCLUSION: Our cases
      demonstrate the variety of clinical presentations of allergic contact dermatitis
      from acrylic nails. They show the need to warn patients of persistent and
      sometimes permanent side effects of these nails. They also emphasize the
      importance of cosmetic ingredient labeling.

PMID- 22398235
TI  - Letter:Annular atrophic lichen planus of the lip.
AB  - Annular atrophic lichen planus is a rare form of lichen planus, clinically
      characterized by a circumscribed annular configuration. We report herein a 32
      year-old female who developed depressed plaques on the lips. Physical examination
      showed well-circumscribed, erythematous plaques on the lower lip. The border was
      slightly elevated and the inner portion was depressed and atrophic. Also, a bean
      sized well-circumscribed plaque with slightly elevated border was found on the
      upper lip. A biopsy specimen revealed that the epithelium of the mucous membrane
      was reduced in thickness and a mononuclear cell infiltration invaded the basement
      membrane of the epithelium. This is the first case of annular atrophic lichen
      planus involving the lip. She was treated with 0.1 percent tacrolimus ointment
      once daily, which resulted in a beneficial effect.

PMID- 22398236
TI  - Letter: Isolated annular lichen planus of lower lip.
AB  - Lichen planus (LP), the prototype of lichenoid dermatoses, is an idiopathic
      inflammatory disease of the skin and mucous membranes, hair follicles, and nails.
      It rarely occurs on the lips and usually then in association with oral lesions.
      We report a 40-year-old man with a 3-month history of an isolated single annular
      violaceous plaque of the lower lip. The rest of his mucosae, skin, hair and nails
      were normal. Histopathology confirmed the diagnosis of LP. The patient was
      advised to use topical tacrolimus 0.03 percent cream twice daily along with
      multivitamins, but the patient was lost to follow-up. Isolated LP of the lip is
      unusual, although this condition may be underestimated and therefore under
      reported in the literature.

PMID- 22398237
TI  - Letter: The "reading man" flap in facial reconstruction: report of 12 cases.
AB  - Reconstruction of defects in the infraorbital, malar, and temporal areas after
      tumor resection may present problems such as distortion of anatomic points and
      extra normal skin removal. The "reading man" flap is a recent local flap
      procedure, which has been used to solve those problems. We report our experience
      with this procedure, which has been used for the closure of circular defects in
      12 patients (7 men and 5 women), aged 68 to 86 years (mean age: 77 years), who
      had undergone surgical excisions of basal cell carcinomas of the temporal, malar,
      and infraorbital regions. The functional and aesthetical results were
      satisfactory in all cases. In our experience, the "reading man" flap is a useful
      option for the reconstruction of circular defects in these facial areas.

PMID- 22398238
TI  - Back to the roots of chronic obstructive pulmonary disease: the severity of
      respiratory impairment matters.

PMID- 22398239
TI  - Modelling and simulation of the influence of acute and chronic hypoxia on
      [18F]fluoromisonidazole PET imaging.
AB  - Tumour hypoxia can be assessed by positron emission tomography (PET) using
      radiotracers like [(18)F]fluoromisonidazole (Fmiso). The purpose of this work was
      to independently investigate the influence of chronic and acute hypoxia on the
      retention of Fmiso on the microscale. This was approached by modelling and
      simulating tissue oxygenation and Fmiso dynamics on the microscale based on
      tumour histology. Diffusion of oxygen and Fmiso molecules in tissue- and oxygen
      dependent Fmiso binding were included in the model. Moreover, a model of
      fluctuating vascular oxygen tension was incorporated to theoretically predict the
      effects of acute hypoxia. Simulated tissue oxygen tensions (PO(2)) are strongly
      influenced by the modelled periodical fluctuations (period 40 min, total
      amplitude 10 mmHg and mean 35 mmHg). Fluctuations led to variations in mean PO(2)
      of up to 41% and in the hypoxic fraction (PO(2)  < 5 mmHg) from 56% up to 65%.
      Significant Fmiso retention is caused by chronic (87%) as well as acute hypoxia
      (13%). By simulating Fmiso injection during different phases of the vascular
      PO(2) fluctuation cycle, it was found that acute hypoxia of an empirically valid
      magnitude does not influence the reproducibility of PET imaging. Thus, it may be
      impossible to separate acute and chronic hypoxia from serial PET images.

PMID- 22398240
TI  - Mitochondria-derived reactive intermediate species mediate asbestos-induced
      genotoxicity and oxidative stress-responsive signaling pathways.
AB  - BACKGROUND: The incidence of asbestos-induced human cancers is increasing
      worldwide, and considerable evidence suggests that reactive oxygen species (ROS)
      are important mediators of these diseases. Our previous studies suggested that
      mitochondria might be involved in the initiation of oxidative stress in asbestos
      exposed mammalian cells. OBJECTIVE: We investigated whether mitochondria are a
      potential cytoplasmic target of asbestos using a mitochondrial DNA-depleted
      (rho(0)) human small airway epithelial (SAE) cell model: rho(0) SAE cells lack
      the capacity to produce mitochondrial ROS. METHODS: We examined nuclear DNA
      damage, micronuclei (MN), intracellular ROS production, and the expression of
      inflammation-related nuclear genes in both parental and rho(0) SAE cells in
      response to asbestos treatment. RESULTS: Asbestos induced a dose-dependent
      increase in nuclear DNA oxidative damage and MN in SAE cells. Furthermore, there
      was a significant increase in intracellular oxidant production and activation of
      genes involved in nuclear factor kappaB and proinflammatory signaling pathways in
      SAE cells. In contrast, the effects of asbestos were minimal in rho(0) SAE cells.
      CONCLUSIONS: Mitochondria are a major cytoplasmic target of asbestos. Asbestos
      may initiate mitochondria-associated ROS, which mediate asbestos-induced nuclear
      mutagenic events and inflammatory signaling pathways in exposed cells. These data
      provide new insights into the molecular mechanisms of asbestos-induced
      genotoxicity.

PMID- 22398241
TI  - Application of the WHOQOL-100 for the assessment of quality of life of adult
      patients with inherited metabolic diseases.
AB  - BACKGROUND: As advances in neonatal and pediatric care for patients affected by
      inherited metabolic diseases (IMD) improve their outcome and allow for better
      survival rates, there is a growing interest in the quality of life (QoL) of
      patients reaching adulthood. In order to address this subject we designed a study
      to evaluate the QoL of a group of adult IMD patients who are receiving various
      treatments, in a comprehensive manner. METHODS: A mixed-method study was
      conducted to assess the QoL in adult IMD patients. The multidimensional World
      Health Organization Quality of Life questionnaire (WHOQOL-100) was applied for
      quantitative evaluations, and an additional semi-standardized interview, was
      conducted for qualitative measurement of patients' perceptions of the impact of
      illness on their daily life, and the perceived adherence to their treatment
      recommendations. A total of 82 patients affected by IMD were enrolled. The
      inherited metabolic disorders included principally amino acids disorders, urea
      cycle defects, organic acidurias, carbohydrates disorders, and lysosomal
      disorders. The WHOQOL-100 and the semi-standardized interview were administered
      in a clinical setting to adult patients with IMD. RESULTS: The mean for the whole
      group indicates that adult patients with IMD can have a normal value of General
      QoL. Despite this value, the results of each domain show lower scores in the
      domains of perception of independence and quality of social relationships. We
      made a further analysis to compare the patients with dietary treatment with the
      patients with pharmacological treatment, and we observed a statistically
      significant difference in General QoL, in the Physical, Independence, Spiritual
      domains and in the facet of Medication. These results suggest that Global QoL
      measures might not be sufficient to assess the QoL for adult patients with IMD.
      Furthermore, the implementation of a qualitative semi-standardized interview,
      especially suitable for adult patients, added important features on illness
      perception and on perceived adherence to the treatment by adult IMD patients.
      CONCLUSION: In this study we underlined the importance of applying
      multidimensional instruments, like WHOQOL-100, to evaluate the quality of life of
      adult patients with IMD. The WHOQOL-100 has been demonstrated to be a valid
      instrument to measure the QoL of IMD patients. Moreover, the administration of a
      tailored psychometric instrument in combination with a qualitative interview may
      help us to better characterize special issues related to IMD. Indeed, other
      factors beyond the physical manifestations of the disease, such as psychological
      wellbeing, social behavior, illness perception and adherence to the treatment,
      strongly influence QoL and may serve as valid targets for intervention to improve
      patients' care. We believe this kind of approach is especially useful for adult
      patients with inherited metabolic diseases.

PMID- 22398242
TI  - Large area tunable arrays of graphene nanodots fabricated using diblock copolymer
      micelles.
AB  - Nanostructured graphenes such as nanoribbons, nanomeshes, and nanodots have
      attracted a great deal of attention in relation to graphene-based semiconductor
      devices. The block copolymer micellar approach is a promising bottom-up technique
      for generating large area nanostructures of various materials without using
      sophisticated electron-beam lithography. Here we demonstrate the fabrication of
      an array of graphene nanodots with tunable size and inter-distance  with the
      utilization of a monolayer of diblock copolymer micelles. Au nanoparticles were
      synthesized in the micellar cores and effectively worked as shielding
      nanostructures in generating graphene nanodots by oxygen plasma etching. We also
      controlled the radius and inter-distance of graphene nanodots simply through the
      molecular weight of the copolymers.

PMID- 22398244
TI  - Cytomegalovirus-induced effector T cells cause endothelial cell damage.
AB  - Human cytomegalovirus (CMV) infection has been linked to inflammatory diseases
      that involve vascular endothelial cell damage, but definitive proof for a direct
      cytopathic effect of CMV in these diseases is lacking. CMV infection is
      associated with a strong increase in both CD4(+) and CD8(+) T cells with
      constitutive effector functions that can perpetuate systemic inflammation. We
      investigated whether CMV-induced immune responses could lead to endothelial
      damage in humans. We found that terminally differentiated effector CD4(+) and
      CD8(+) T cells, formed during primary CMV infection and maintained throughout
      latency, express high levels of CX3CR1 and CXCR3. The ligands of these receptors,
      fractalkine and IP-10, respectively, are expressed by activated endothelial
      cells. Peripheral blood mononuclear cells (PBMC) stimulated with CMV antigen
      produced soluble factors that stimulated endothelial cells to produce both
      chemokines. Finally, effector cells migrated in a fractalkine- and IP-10
      dependent fashion to activated endothelial cells and induced apoptosis in
      endothelial cells that were stimulated by supernatant from CMV-activated PBMC.
      Our findings offer an explanation for the accumulation of highly differentiated T
      cells near to the endothelium in CMV-infected individuals that may result in
      endothelial damage.

PMID- 22398243
TI  - DNA and modified vaccinia virus Ankara vaccines encoding multiple cytotoxic and
      helper T-lymphocyte epitopes of human immunodeficiency virus type 1 (HIV-1) are
      safe but weakly immunogenic in HIV-1-uninfected, vaccinia virus-naive adults.
AB  - We evaluated a DNA plasmid-vectored vaccine and a recombinant modified vaccinia
      virus Ankara vaccine (MVA-mBN32), each encoding cytotoxic and helper T-lymphocyte
      epitopes of human immunodeficiency virus type 1 (HIV-1) in a randomized, double
      blinded, placebo-controlled trial in 36 HIV-1-uninfected adults using a
      heterologous prime-boost schedule. HIV-1-specific cellular immune responses,
      measured as interleukin-2 and/or gamma interferon production, were induced in 1
      (4%) of 28 subjects after the first MVA-mBN32 immunization and in 3 (12%) of 25
      subjects after the second MVA-mBN32 immunization. Among these responders,
      polyfunctional T-cell responses, including the production of tumor necrosis
      factor alpha and perforin, were detected. Vaccinia virus-specific antibodies were
      induced to the MVA vector in 27 (93%) of 29 and 26 (93%) of 28 subjects after the
      first and second immunizations with MVA-mBN32. These peptide-based vaccines were
      safe but were ineffective at inducing HIV-1-specific immune responses and induced
      much weaker responses than MVA vaccines expressing the entire open reading frames
      of HIV-1 proteins.

PMID- 22398245
TI  - Reduced frequencies and heightened CD103 expression among virus-induced CD8(+) T
      cells in the respiratory tract airways of vitamin A-deficient mice.
AB  - Vitamin A deficiency (VAD) has profound effects on immune responses in the gut,
      but its effect on other mucosal responses is less well understood. Sendai virus
      (SeV) is a candidate human parainfluenza virus type 1 (hPIV-1) vaccine and a
      candidate vaccine vector for other respiratory viruses. A single intranasal dose
      of SeV elicits a protective immune response against hPIV-1 within days after
      vaccination. To define the effect of VAD on acute responses toward SeV, we
      monitored both antibodies and CD8(+) T cells in mice. On day 10 following SeV
      infection, there was a trend toward lower antibody activities in the nasal washes
      of VAD mice than in those of controls, while bronchoalveolar lavage (BAL) fluid
      and serum antibodies were not reduced. In contrast, there was a dramatic
      reduction of immunodominant CD8(+) T cell frequencies in the lower respiratory
      tract (LRT) airways of VAD animals. These T cells also showed unusually high
      CD103 (the alphaE subunit of alphaEbeta7) expression patterns. In both VAD and
      control mice, E-cadherin (the ligand for alphaEbeta7) was better expressed among
      epithelial cells lining the upper respiratory tract (URT) than in LRT airways.
      The results support a working hypothesis that the high CD103 expression among T
      cell populations in VAD mice alters mechanisms of T cell cross talk with URT and
      LRT epithelial cells, thereby inhibiting T cell migration and egress into the
      lower airway. Our data emphasize that the consequences of VAD are not limited to
      gut-resident cells and characterize VAD influences on an immune response to a
      respiratory virus vaccine.

PMID- 22398247
TI  - New enzyme-linked immunosorbent assay for detection of antibodies against
      hepatitis delta virus using a hepatitis delta antigen derived from a Taiwanese
      clone and comparison to the Abbott radioimmunoassay.
AB  - An anti-hepatitis delta (HD) enzyme-linked immunosorbent assay (ELISA) using a
      specific recombinant hepatitis delta antigen derived from a local dominant
      hepatitis delta virus (hepatitis D virus; HDV) strain in Taiwan has been
      established. The detection efficiency of this assay was comparable to that of the
      commercially available Abbott anti-HD radioimmunoassay (RIA) and could be useful
      in routine laboratory diagnoses of HDV infection.

PMID- 22398246
TI  - Risk of invasive Haemophilus influenzae type b (Hib) disease in adults with
      secondary immunodeficiency in the post-Hib vaccine era.
AB  - Prior to the introduction of Haemophilus influenzae type b (Hib) conjugate
      vaccines, invasive Hib disease affected almost exclusively children. According to
      some recent studies, in the postvaccine era, adults, the elderly, and
      immunocompromised persons can be affected more often than children. As the
      production of type-specific anti-capsular polysaccharide antibodies is the major
      defense mechanism against Hib, individuals with defects in humoral immune
      responses have high susceptibility to infections caused by Hib. We hypothesized
      that nonvaccinated adults with chronic conditions causing immunosuppression may
      lack protective antibody to Hib. We assessed serum anti-Hib IgG levels and
      bactericidal activity in 59 patients with chronic renal failure, 30 patients with
      type 2 diabetes mellitus, 28 patients with chronic obstructive pulmonary disease
      (COPD), and 20 patients with multiple myeloma compared to 32 healthy controls of
      similar age. Considering antibody at >0.15 MUg/ml as the protective correlate in
      unvaccinated individuals, we detected subprotective Hib antibody levels in 29% of
      chronic renal failure, 20% of diabetes, 14% of COPD, and 55% of myeloma patients
      compared to 3% of healthy controls. Additionally, 70% of myeloma and 58% of
      chronic renal failure patients did not have detectable serum bactericidal
      activity against Hib. Among individuals with severe diseases causing secondary
      immunodeficiency, patients with multiple myeloma and chronic renal failure are at
      an increased risk of invasive Hib disease. Considering that Hib continues to
      circulate in the population, this study provides a rationale for the immunization
      of some adult patients with secondary immunodeficiency with the pediatric Hib
      vaccine to achieve protective immunity.

PMID- 22398248
TI  - Humoral immune responses in a human case of glanders.
AB  - Within 2 months of acquiring glanders, a patient developed 8-, 16-, and 4-fold
      increases, respectively, in specific IgA, IgG, and IgM serological titers against
      Burkholderia mallei. Within 14 months of infection, the titers decreased to the
      baseline. Serum from this patient was also highly reactive against Burkholderia
      pseudomallei whole cells. Burkholderia mallei whole cells did not react with sera
      from patients with other diseases. Therefore, an assay using a B. mallei cellular
      diagnostic antigen may be useful for the serodiagnosis of glanders.

PMID- 22398249
TI  - Multisite arterial thrombosis: synchronous or metachronous?

PMID- 22398250
TI  - Genome wide computational analysis of Brugia malayi helicases: a comparison with
      human host.
AB  - The availability of Brugia malayi genome sequence has paved ways for the search
      of homologues for a variety of genes. Helicases are ubiquitous enzymes involved
      in all the nucleic acid metabolic pathways and are essential for the development
      and growth. The genome wide analysis of B. malayi for different helicases showed
      the presence of a number of DEAD box helicases, 7 DEAH box helicases, RecQ
      helicases, repair helicases, super killer helicases, MCM2-7 complex, Rad54 and
      two subunits of Ku helicase. The comparison of protein sequence of each helicase
      with its human counterpart indicated characteristic differences in filarial
      helicases. There are noticeable differences in some of the filarial helicases
      such as DHX35, RecQL1 and Ku. Further characterization of these helicases will
      help in understanding physiological significance of these helicases in filarial
      parasites, which in future can be utilized for chemotherapy of parasitic
      infection.

PMID- 22398251
TI  - Investigation of mortality in Pacific oysters associated with Ostreid herpesvirus
      1 MUVar in the Republic of Ireland in 2009.
AB  - High levels of mortality in Pacific oysters Crassostrea gigas in the Republic of
      Ireland were recorded during the summer of 2009. The new variant of Ostreid
      herpes 1 (OsHV-1 MUVar) which first emerged in France in 2008 was identified from
      affected stocks. Retrospective data was collected from 70 oyster farmers through
      an interviewer-administered questionnaire to investigate the distribution and
      determinants of the mortality. Based on farmer recall, data were recorded at the
      batch level for cumulative mortality during 2009, start dates and duration of the
      mortality event and the age of animals affected. Observable mortalities were
      recorded in 109 out of 346 batches at 47 sites; 104 of the 109 batches were
      located in bays where OsHV-1 MUVar had been detected. The records from bays where
      OsHV-1 MUVar had been detected were analysed to characterize the pattern of
      mortality and potential risk factors. Batch mortality averaged 37% (18-65%
      quartiles) but showed a bimodal distribution (half the batches had mortality less
      than 45%). Mortalities started at the end of May and continued until early
      August, peaking in early July. On average oysters died over a period of 18 days.
      Mortality varied considerably both between and within bays. Mortality started in
      recently introduced batches and occurred later in the summer in established
      oysters, which is consistent with the introduction of an infectious agent.
      Mortality was significantly lower in adults compared with other age groups, which
      supports observations from France. Three variables were significantly (P<0.05)
      associated, in both bivariate screening and a logistic regression, with high
      batch-level mortality (>40%): oysters (i) introduced as juveniles, (ii) during or
      since the winter of 2008/9 and (iii) which spent less than 8h out of water (in a
      tidal cycle) (compared with oysters introduced as adults before the winter of
      2008/9 and spending more than 8h out of water). Twenty-one percent of triploid
      batches experienced "high" (>40%) mortality compared with 10% for diploid batches
      which was significant (P<0.05) in the initial bivariate screening but not in the
      final logistic regression model. Future studies should develop improved methods
      to assess oyster mortality and follow stocks over time to better determine the
      influence of management and environmental factors on mortality.

PMID- 22398252
TI  - Bovine tuberculosis surveillance alternatives in Belgium.
AB  - Belgium obtained the bovine tuberculosis (bTB) officially free status in 2003 (EC
      Decision 2003/467/EC). This study was carried out to evaluate the components of
      the current bTB surveillance program in Belgium and to determine the sensitivity
      of this program. Secondly, alternatives to optimize the bTB surveillance in
      accordance with European legislation (Council Directive 64/432/EEC) were
      evaluated. Separate scenario trees were designed for each active surveillance
      component of the bTB surveillance program. Data from 2005 to 2009 regarding
      cattle population, movement and surveillance were collected to feed the
      stochastic scenario tree simulation model. A total of 7,403,826 cattle movement
      history records were obtained for the 2,678,020 cattle from 36,059 cattle herds
      still active in 2009. The current surveillance program sensitivity as well as the
      impact of alternative surveillance protocols was simulated in a stochastic model
      using 10,000 iterations per simulation. The median (50% percentile) of the
      component sensitivities across 10,000 iterations was 0.83, 0.85, 0.99, 0.99,
      respectively, for (i) testing the cattle only during the winter screening, (ii)
      testing only imported cattle, (iii) testing only purchased cattle and (iv)
      testing only all slaughtered cattle. The sensitivity analysis showed that the
      most influential input parameter explaining the variability around the output
      came from the uncertainty distribution around the sensitivity of the diagnostic
      tests used within the bTB surveillance. Providing all animals are inspected and
      post mortem inspection is highly sensitive, slaughterhouse surveillance was the
      most effective surveillance component. If these conditions were not met, the
      uncertainty around the mean sensitivity of this component was important. Using an
      antibody ELISA at purchase and an interferon gamma test during winter screening
      and at import would increase greatly the sensitivity and the confidence level of
      Belgium's freedom from bTB infection status.

PMID- 22398253
TI  - Faecal occult blood test and iron deficiency anaemia.

PMID- 22398254
TI  - Synthesis of a tetrasaccharide analog corresponding to the repeating unit of the
      O-polysaccharide of Salmonella enterica O59: unexpected stereo outcome in
      glycosylation.
AB  - Convergent synthesis of a tetrasaccharide analog corresponding to the repeating
      unit of the O-polysaccharide of Salmonella enterica O59 is presented. A
      thioglycoside disaccharide donor was prepared by the glycosylation of two
      thioglycosides by tuning their relative reactivity. An unexpected stereochemical
      outcome was observed in a glycosylation using an ethyl 2-O-acetyl-3-O-benzyl-4,6
      O-bensylidene-thio-galactoside donor, where the alpha-galactoside was formed in
      spite of the presence of the 2-O-acetyl participating group.

PMID- 22398255
TI  - Structural characterization of polysaccharides isolated from grape stalks of
      Vitis vinifera L.
AB  - The main structural polysaccharides of grape stalks are cellulose, heteroxylan,
      and glucan. Cellulose contributes 30.3% of grape stalk matter and has an
      unusually high degree of the crystallinity (75.4%). Among hemicelluloses, xylan
      was the most abundant one, contributing ~12% to the weight. The heteroxylan was
      isolated from the corresponding peracetic holocellulose by DMSO extraction
      followed by precipitation in ethanol. The M(w) of heteroxylan (19.0 kDa) was
      assessed by size exclusion chromatography (SEC) and the structure was inferred by
      methanolysis and methylation linkage analysis, as well as 1D and 2D nuclear
      magnetic resonance (NMR) spectroscopy. The heteroxylan is a partially acetylated
      (DS=0.49) glucuronoxylan possessing the main backbone composed by beta-(1->4)
      linked D-xylopyranosyl units ramified with alpha-(1->2)-linked 4-O-methyl-alpha-D
      glucuronosyl residues (MeGlcpA) at a molar ratio 25:1. The isolated heteroxylan
      contained concomitant beta-glucan (ca. 15%), whose structure was elucidated by
      methylation linkage analysis and by NMR spectroscopy. The results obtained
      revealed mixed beta-(1->3; 1->4)-D-glucan with a molar ratio of beta-(1->3)- to
      beta-(1->4)-linked glucopyranosyl units of 1:2.

PMID- 22398256
TI  - [Effect of body mass index on PSA in northeast Mexican patients].
AB  - OBJECTIVE: To evaluate the effect of body mass index (BMI) on PSA in northeast
      Mexican patients included in prostate cancer (Pca) early detection screening
      campaigns offered by our institution. MATERIAL AND METHODS: One hundred and
      ninety seven patients came voluntarily to our Pca early detection screening
      campaigns. EXCLUSION CRITERIA: PSA >10 ng/dl, patients on 5-alpha Reductase
      inhibitors or hormonal replacement. Overweight and obesity were considered when
      BMI was between 25-29.9 and >=30 kg/m(2) respectively. Simple linear and multiple
      regression were used in the statistical analysis. Mean and standard deviation
      were utilized to evaluate spread and normal distribution. P values <0.05 were
      considered statistically significant. RESULTS: One hundred and fifty two patients
      were included in this study. Forty four percent (83) and 30.3%(46) presented with
      overweight and obesity, respectively. Mean BMI was 28.16 kg/m(2) (SD 1.77). A
      statistically significant negative effect of BMI on PSA was observed in the
      linear regression. This effect persisted when adjusted for age in the multiple
      regression model. A decrease of 0.085 ng/dl for every unit of BMI (p <0.001) was
      observed in the simple linear regression. This value was 0.07 in the multiple
      regression (p=0.006) CONCLUSIONS: A higher negative effect of BMI on PSA was
      found in comparison to published literature. A higher proportion of patients with
      BMI >25 kg/m(2) than the national mean was observed. A multicentric national
      study is needed in order to challenge these results.

PMID- 22398257
TI  - Threshold values of follicle count for the definition of PCO.

PMID- 22398258
TI  - Synthesis and evaluation of disulfide bond mimetics of amylin-(1-8) as agents to
      treat osteoporosis.
AB  - Osteoporotic fracture is a significant public health problem, resulting in
      fractures in >50% of women and in almost one third of men age 65 and older. Most
      of the existing therapies act by slowing bone loss, through inhibiting the action
      of bone resorbing cells. However, more substantial reductions of fracture numbers
      will only result from treatments that can rebuild bone. Our own animal studies
      demonstrated the anabolic potential of the small but unstable octapeptide
      fragment of amylin-(1-37), namely amylin-(1-8) containing one disulfide bridge
      (Cys/2 and Cys/7) [Am. J. Physiol. Endocrinol. Metab.2000, 279, E730]. Herein, we
      describe the synthesis of amylin-(1-8) octapeptide and seven analogues thereof
      wherein the disulfide bridge is modified either via insertion of different
      linkers or bridges of a different nature in order to improve the stability and/or
      bone anabolic activity of the parent peptide. The peptide analogues were screened
      for proliferative activity in primary foetal rat bone-forming cells or
      osteoblasts at physiological concentrations. One such analogue showed promising
      biological activity.

PMID- 22398260
TI  - Atypical presentation of cauda equina syndrome secondary to lumbar disc
      herniation.
AB  - The article describes the case of 35 year old female who was admitted to the
      department with saddle type hypoesthesia, anal incontinence without muscle
      weakness of lower extremities and sciatica. Central lumbar disc herniation (LDH)
      was determined on level L5-S1 level and the patient was operated thereafter. In
      the postoperative period, the patient did not have any muscle weakness of leg but
      had residual saddle type sensory loss and sphincter dysfunction. This article
      discusses atypical presentation of cauda equina syndrome (CES) secondary to LDH.
      Early diagnosis and surgery are important factors for a better prognosis in CES.

PMID- 22398259
TI  - Synthesis and structure-activity relationship studies of 3-biaryl-8
      oxabicyclo[3.2.1]octane-2-carboxylic acid methyl esters.
AB  - Stille cross coupling protocols were utilized for the synthesis of 3-(biaryl)-8
      oxabicyclo[3.2.1]oct-2-ene-2-carboxylic acid methyl esters, which furnished
      products in high yields where in some cases Suzuki coupling under the conditions
      utilized provided complex reaction mixture. Samarium iodide reduction of the
      resulting coupling products produced both of the 2beta-carbomethoxy-3-biaryl-8
      oxabicyclo[3.2.1]octane diastereomers and the 2alpha-carbomethoxy-3-biaryl-8
      oxabicyclo[3.2.1]octane diastereomers. Among the series synthesized, the
      benzothiophene substituted compounds demonstrated significant binding profiles of
      inhibition of WIN 35,438 with 177-fold selectivity for DAT versus SERT.

PMID- 22398261
TI  - Are there work-related musculoskeletal problems among teachers in Samsun, Turkey?
AB  - INTRODUCTION: The aim of this study was to evaluate the prevalence of work
      related musculoskeletal pain (WRMSP) and depression and the quality of life (QOL)
      among teachers in Samsun, Turkey. MATERIALS AND METHODS: Among 605~participants
      99.30% (n=602) completed the survey. A face-to-face questionnaire was given to
      the participiants in order to evaluate the QOL (Short Form 36, SF-36), the
      presence of depression (Beck Depression Inventory, BDI) and the presence of pain
      (Visual Analogue Scale). RESULTS: Among the participants (n=602), 290 were women
      (48%) and 312 were men (52%). Three hundred sixty three (60.3%) of the
      participants reported that they had work-related pain. Most of the participants
      had WRMSP in low back (74.9%), shoulder (55.9%), neck (47.9%), back (42.7%), knee
      (30.9%) regions. There was a significant difference for BDI and the subscales of
      SF-36 test, except the emotional role limitation, mental health and energy
      between the participiants with WRMSP (Group 1) and the participiants without
      WRMSP (Group 2). BDI scores were significantly higher in the Group 1. The
      subscale scores of SF-36 were significantly lower in the Group 1. There was a
      negative correlation between SF-36 and BDI scores; indicating that teachers who
      have more depressive symptoms have also a lower QOL. CONCLUSIONS: Pain in neck,
      shoulder, back and low back regions are frequently seen in teachers. Depression
      is common and its presence reduces the QOL of teachers. Modifications of
      ergonomics in working conditions may reduce the frequency of these complications.
      The habit of carrying heavy loads, awkward back postures, longterm repetitive
      physical activities, psychosocial stressors and longterm standing must be
      reduced.

PMID- 22398262
TI  - The beneficial effects of adding low level laser to ultrasound and exercise in
      Iranian women with shoulder tendonitis: a randomized clinical trial.
AB  - OBJECTIVES: A randomized, double-blind, clinical trial study was conducted with
      the aim of determining the efficacy of adding laser (830 nm) to ultrasound (US)
      and exercise for the management of shoulder tendonitis. METHODS: 42 subjects
      (n=21, in adding laser group and n=21, in US and exercise group) received a
      course of 10 sessions treatment over one month in the shoulder region. Outcome
      measures such as Visual Analogue Scale (VAS), Tenderness Severity Scale (TSS),
      Constant Murley Score (CMS) and Manual Muscle Testing (MMT) were performed before
      treatment and at the end of 4 weeks treatment. In addition, follow up were
      performed 2 months after the end of treatment based on the degree of pain
      improvement. RESULTS: VAS, TSS and CMS improved significantly (P=0.001) in both
      groups, however the muscle strengths only improved significantly in adding laser
      group (P< 0.01). CONCLUSION: It seems that both protocols of physical therapy
      interventions were effective in relieving the signs and symptoms of shoulder
      tendonitis. Furthermore, adding low level laser therapy (LLLT) to the US and
      exercise was more efficient in improving the muscle strength in patients with
      shoulder tendonitis over a period of three months. However, it should be
      emphasized that, the current results might be due to the effects of laser and
      exercise instead of laser, us and exercise (as we had no independent group for
      US).

PMID- 22398263
TI  - Differences of ground reaction forces and kinematics of lower extremity according
      to landing height between flat and normal feet.
AB  - The study compared lower extremity kinematics and kinetics between male subjects
      with flat and normal feet when landing on both feet from platforms at different
      heights. Ten subjects with a flat feet arch and 10 subjects with a normal foot
      arch were recruited. They performed a double limb drop landing from 20, 40, and
      60 cm onto a force-plate. A three-dimensional motion analysis system, force
      plates, and electromyography were used to analyze lower extremity kinetic and
      kinematic data. The GRF and angle of sagittal plane significantly increased with
      landing height in the flat foot group. In particular, hip joint angles at a
      height of 60 cm were significantly greater. The electromyography values were
      significantly higher for the tibialis anterior and vastus lateralis muscles, but
      were significantly lower in the abductor hallucis, gastrocnemius, and biceps
      femoris muscles in the flat foot group. GRF, joint angles, and muscle activity
      patterns in the lower extremities increases more with height in flat footed
      individuals than in people with a normal foot arch. Flat feet may aggravate the
      risk of shock on landing from a height; this might be ameliorated by a
      compensatory strategy at the hip joints to facilitate load distribution.

PMID- 22398264
TI  - Changes in recruitment of pelvic stabilizer muscles in people with and without
      sacroiliac joint pain during the active straight-leg-raise test.
AB  - BACKGROUND: Though the active straight leg raise (ASLR) test has been proposed as
      a reliable methodology for assessment of load transfer through the pelvis in
      patients with sacroiliac joint pain (SIJP), the tonicity and timing of muscle
      activation during the ASLR test have not been investigated. In clinical
      experiments, besides the ASLR test score, an increased duration of the test is
      also used for diagnosis of SIJP. OBJECTIVE: This study was a cross-sectional
      design of electro-myographic pattern of sacroiliac stabilizer muscles to
      establish a platform for comparison of patients with SIJP and healthy controls.
      To identify if the subjects with SIJP show changes in electromyographic pattern
      of sacroiliac stabilizer muscles as well as any duration difference in such tests
      for both groups. METHODS: Fifteen female patients with sacroiliac pain and the
      same number of healthy females at the same age were participated in this study.
      All the patients were diagnosed as positive ASLR as well as self reported maximum
      pain over the sacroiliac joint. Surface electromyographic activity was recorded
      from rectus abdominus, external oblique, internal oblique, adductor longus,
      biceps femoris, gluteus maximus and erector spinea during ASLR. Tonicity and
      onset of muscle activity in relation to the initiation of the ASLR and their
      duration were also compared. RESULTS: The participants with SIJP exhibited a
      significantly increased latency at the onset of adductor longus following the
      initiation of the ASLR test (P=0.002) as compared to the healthy controls. A
      significant difference was also observed in tonicities of external oblique,
      biceps femoris, gluteus maximus and erector spinea as well as the duration of leg
      rising (P < 0.05) between the two groups. CONCLUSION: These findings suggest that
      an alteration in the motor control strategy for lumbopelvic stabilization in
      patients with SIJP may influence load transfer through the pelvic.

PMID- 22398265
TI  - Handrail position and shape that best facilitate sit-to-stand movement.
AB  - BACKGROUND: Sit-to-stand (STS) movement is an important part of the overall
      pattern of walking and affects social independence. OBJECTIVE: We examined the
      kinematics of STS movement using two adjustable handrails. METHODS: Seventy-five
      subjects (25 college students, 25 independent elderly people, and 25 physically
      challenged elderly people) participated in the study. Five types of handrail
      positions ('no handrails', 'both high', 'both low', 'high and low' and 'reverse
      high and low') were evaluated. Kinematic data were collected using a VICON
      analyzer and a Myosystem was used to collect the electromyographic data. RESULTS:
      STS movements with high and low handrails in the elderly subjects took the
      shortest time and showed the largest decrease in torque (15%) compared to no
      handrails. The 'high and low' position also reduced the loads to the greatest
      extent. The average time period for STS was reduced by 15 to 30% using the high
      and low handrails compared to no handrail for all three groups. CONCLUSION: The
      'high and low' handrail position best facilitates STS movement in the elderly by
      reducing the time needed to perform STS movements and by reducing the torque and
      subsequent wear on the joints and muscles.

PMID- 22398266
TI  - Three-dimensional characteristics of neck movements in subjects with mechanical
      neck disorder.
AB  - STUDY DESIGN: Controlled laboratory study. OBJECTIVES: To examine characteristics
      of neck movement at three-dimensional planes for subjects with mechanical neck
      disorder (MND) and measure cervical range of motion, coupling motion, and
      calculation of the upper cervical rotation ratio. BACKGROUND: MND is
      characterized by symptoms of neck pain, headache, dizziness and limited range of
      motion (ROM). However, the characteristics of neck movements across the three
      dimensional planes in MND patients remain unknown. METHODS: Forty participants
      were recruited, which consisted of twenty-seven subjects with MND and 13 healthy
      subjects. A three-dimensional electromagnetic motion capture device with custom
      data analysis software was used to measure the neutral position of the neck and
      the range of motion of upper and lower cervical spine. RESULTS: The results
      indicate that subjects with MND had significantly decreased ROM in right rotation
      (p< 0.05) and extension (p< 0.05) movements compared to the healthy group.
      Increased coupling motion (p< 0.05) in the rotation plane during cervical flexion
      was also found in the MND group compared to control group. For rotations in
      neutral or in flexion positions, rotation to the right showed smaller range of
      motion compared to rotation to the left. CONCLUSION: In this study, MND was
      associated with altered cervical movement patterns with increases in coupling
      motion. The findings may help to differentiate MND from whiplash-associated
      disorder. Increasing upper cervical spine rotation mobility may be crucial for
      treating deficiencies in neck rotation in patients with MND.

PMID- 22398267
TI  - Postural profile and falls of osteoporotic women.
AB  - OBJECTIVES: 1. To compare postural alignment in erect standing between
      osteoporotic fallers, osteoporotic non-fallers and healthy women. 2. To compare
      BMI, number of fractures and intensity of pain between osteoporotic fallers and
      non-fallers. METHODS: Thirty-six osteoporotic women with vertebral fractures and
      40 healthy women participated in the study. Spinal curvatures were assessed with
      a digital inclinometer. Photographic measurements of knee, hip, shoulder and head
      were carried out in sagittal plane. RESULTS: Significant differences were found
      between osteoporotic fallers and healthy women in the head (p=0.040), and
      thoracic angles (p=0.001). Significant differences were found between fallers and
      non-fallers in BMI (p=0.000), number of fractures (p=0.033) and pain (p=0.005),
      with fallers being heavier, with less fractures and pain than non-fallers.
      CONCLUSIONS: Osteoporotic fallers probably differ from osteoporotic non-fallers
      and healthy women. Researchers and clinicians may consider, in the future, the
      above differences when planning research and clinical intervention in this field.
      Replication studies are necessary to confirm the present findings.

PMID- 22398268
TI  - The sign of unilateral neck semispinalis capitis muscle atrophy in patients with
      chronic non-specific neck pain.
AB  - BACKGROUND AND OBJECTIVES: Neck muscles have a major role in normal stability and
      mobility of cervical spine in healthy subjects. Weakness and related atrophy of
      these muscles may be a causative factor in cervical pain among office workers.
      The aim of this study was to compare the size and asymmetry of the neck
      semispinalis capitis muscle (SECM) between a group of female office workers with
      unilateral chronic non-specific neck pain (CNNP) and a group of healthy control
      subjects. MATERIAL AND METHOD: Twenty female office workers (10 patients with
      unilateral CNNP and 10 healthy subjects) participated in this study. The right
      and left SECM sizes, anterior posterior dimension (APD) and lateral dimension
      (LD) were measured by an ultrasonography apparatus. The size of SECM was
      calculated as APD * LD. RESULTS: The SECM size and the ratio of the size to body
      weight in patients were less than that of controls (P < 0.05, P < 0.001). The
      size of SECM was also smaller in affected side than unaffected side in patients
      group (P < 0.05). Between sides asymmetry of SECM size was higher in patients
      than that of controls (P < 0.001). The mean APD of SECM of patients was less than
      that of controls (P < 0.01). There was not significant difference in LD between
      two groups. CONCLUSIONS: Neck SECM size and asymmetry measurements and the ratio
      of SECM size to body weight as well as APD appeared to be useful parameters to
      detect neck muscle atrophy in patients with CNNP.

PMID- 22398269
TI  - Is there a biological difference between trauma-related depression and PTSD? DST
      says 'NO'.
AB  - The use of the low-dose dexamethasone suppression test (DST) as a potentially
      discriminative marker between post-traumatic stress disorder (PTSD) and
      depression is still under discussion. In order to compare the influence of these
      psychopathologies on the DST results, we examined suppression in war-traumatized
      subjects with one or both of these disorders, as well as in healthy controls.
      Based on our previous findings, we hypothesized that subjects with any disorder
      would exhibit higher dexamethasone suppression than healthy controls due to
      traumatic experiences. This study was a part of a broader project in which
      simultaneous psychological and biological investigations were carried out in
      hospital conditions on 399 male participants: 57 with PTSD, 28 with depression,
      76 with PTSD+depression, and 238 healthy controls. Cortisol was measured in blood
      samples taken at 0900 h before and after administering 0.5mg of dexamethasone (at
      2300 h). Group means +/- standard deviation of cortisol suppression were: 79.4+/
      18.5 in the PTSD group, 80.8+/-11.6 in the depression group, 77.5+/-24.6 in the
      group with PTSD+depression, and 66.8+/-34.6 in healthy controls. The first three
      groups suppressed significantly more than the fourth. When the number of traumas
      was introduced as a covariate, the differences disappeared. The hypothesis was
      confirmed: in respect to DST, the examined trauma-related psychopathologies
      showed the same pattern: hypersuppression, due to multiple traumatic experiences.

PMID- 22398270
TI  - Electrochemical detection of catecholamine release using planar iridium oxide
      electrodes in nanoliter microfluidic cell culture volumes.
AB  - Release of neurotransmitters and hormones by calcium regulated exocytosis is a
      fundamental cellular/molecular process that is disrupted in a variety of
      psychiatric, neurological, and endocrine disorders. Therefore, this area
      represents a relevant target for drug and therapeutic development, efforts that
      will be aided by novel analytical tools and devices that provide mechanistically
      rich data with increased throughput. Toward this goal, we have electrochemically
      deposited iridium oxide (IrOx) films onto planar thin film platinum electrodes
      (20 MUm*300 MUm) and utilized these for quantitative detection of catecholamine
      release from adrenal chromaffin cells trapped in a microfluidic network. The IrOx
      electrodes show a linear response to norepinephrine in the range of 0-400 MUM,
      with a sensitivity of 23.1+/-0.5 mA/M mm(2). The sensitivity of the IrOx
      electrodes does not change in the presence of ascorbic acid, a substance commonly
      found in biological samples. A replica molded polydimethylsiloxane (PDMS)
      microfluidic device with nanoliter sensing volumes was aligned and sealed to a
      glass substrate with the sensing electrodes. Small populations of chromaffin
      cells were trapped in the microfluidic device and stimulated by rapid perfusion
      with high potassium (50mM) containing Tyrode's solution at a flow rate of 1 nL/s.
      Stimulation of the cells produced a rapid increase in current due to oxidation of
      the released catecholamines, with an estimated maximum concentration in the cell
      culture volume of ~52 MUM. Thus, we demonstrate the utility of an integrated
      microfluidic network with IrOx electrodes for real-time quantitative detection of
      catecholamines released from small populations of chromaffin cells.

PMID- 22398271
TI  - Causes of obesity in captive cynomolgus macaques: influence of body condition,
      social and management factors on behaviour around feeding.
AB  - Similar to other primate species, captive cynomolgus macaques (Macaca
      fascicularis) are prone to becoming overweight. The relationship between body
      condition and feeding behaviour in group-housed animals has not been reported.
      This study evaluated the effect of daily feeding routines on behaviour patterns
      in cynomolgus macaques to determine whether overweight macaques displayed
      different behaviours and activity levels. In this prospective observational
      study, 16 macaques (m = 4, f = 12) from four separate troops (n = 4 per troop)
      were selected from a colony of 165 animals. Observational data were collected
      over six months during morning and afternoon feedings by scan sampling.
      Behaviours of interest included foraging, eating, aggressive and positive social
      interactions, inactivity and physical activities. Multivariable mixed logistic
      regression modelling was used for data analysis. Results indicated that
      overweight animals were more likely to be inactive, dominant animals had
      increased probabilities of eating compared with non-dominants, and aggressive
      behaviours were more likely to occur in the morning and before feeding,
      suggesting feeding anticipation. Positive social interaction before feeding was
      seen and may be a strategy used to avoid aggressive encounters around food
      resources. Individual animal caregivers had an unintentional impact on behaviour,
      as decreased eating and an increase in inactivity were noted when certain
      individuals fed animals. These findings illustrate the complexities of feeding
      group-housed cynomolgus macaques to avoid overweight body condition. Feeding
      routines may require more care and attention to distribute food in a way that
      ensures equitable food intake among troop animals, while not disturbing group
      cohesion.

PMID- 22398272
TI  - Oral immunosuppressive medication for growing pigs in transplantation studies.
AB  - Immunosuppressive (IS) medication is needed to avoid graft rejection in porcine
      transplantation models. An ideal IS therapy should have no side-effects, but
      increased susceptibility to infections, disturbed intestinal microflora and toxic
      effects on organs and tissues are commonly reported. The aim of the present study
      was to design an IS protocol with tacrolimus and mycophenolic acid to be used for
      maintenance therapy in the post-transplant period. An eligible whole blood trough
      value for tacrolimus was 5-15 MUg/L. Conventional specific pathogen-free pigs
      were fitted with an indwelling catheter under general anaesthesia, and after the
      acclimatization period three groups were formed: group A (n= 4) received 0.15
      mg/kg body weight (BW) twice daily tacrolimus and 500 mg twice daily mycophenolic
      acid; group B (n= 4) received 0.3 mg/kg BW twice daily tacrolimus and 500 mg
      twice daily mycophenolic acid; group C (n= 2) did not receive any medication.
      Daily clinical examinations and analyses of blood concentrations of tacrolimus
      and glucose were performed. Total and differential white blood cell counts,
      enzyme activities, bilirubin and electrolyte concentrations were measured every
      fourth day. At the end of the experiment, the pigs were killed with an overdose
      of pentobarbital intravenously and a necropsy was performed immediately. All
      animals seemed to tolerate the IS treatment well. No alterations in their
      clinical state of health were observed throughout the study and daily weight gain
      was similar for the three groups. The necropsy did not reveal any pathological
      findings related to medication. The study showed that 0.25 mg/kg BW twice daily
      tacrolimus and 500 mg twice daily mycophenolic acid would be an appropriate
      maintenance dosage for conventional pigs.

PMID- 22398273
TI  - Influence of tail versus cardiac sampling on blood glucose and lipid profiles in
      mice.
AB  - Blood is collected during animal experimentation to measure haematological and
      metabolic parameters. It cannot be assumed that circulating blood has the same
      composition irrespective of its location, and indeed, differences in the
      composition of blood sampled from the arterial and venous compartments have been
      reported. Here we investigated whether blood collected by cardiac puncture (CP)
      versus that collected following removal of the distal 1 mm of the tail tip (TT)
      differs with respect to glucose and lipid profiles in male C57BL/6J mice at 4, 7,
      20 and 28 weeks of age. Blood was first collected from the TT of unanaesthetized
      mice, which were then immediately anaesthetized using ketamine/xylazine, and a
      second blood sample was collected by CP. The CP glucose concentration was
      significantly higher than TT glucose by a positive bias averaging +80% (P <
      0.01), irrespective of the age of the mice. Conversely, the concentrations of the
      CP lipids, including total cholesterol, high-density lipoprotein cholesterol and
      triglyceride were lower than TT lipids by a negative bias averaging -25% (P <
      0.05). These observations highlight the difficulty in measuring and comparing
      metabolic parameters such as glucose and lipid between one blood compartment and
      another. They illustrate the need to standardize sampling sites, especially when
      repeated blood sampling is required.

PMID- 22398274
TI  - Homozygous familial hypercholesterolemia: current perspectives on diagnosis and
      treatment.
AB  - Homozygous familial hypercholesterolemia (HoFH) is an autosomal co-dominant
      disease resulting from mutations in both copies of the low-density lipoprotein
      receptor (LDLR) gene. Mutations in 3 other associated genes, proprotein
      convertase subtilisin/kexin type 9, apolipoprotein B (APOB), and, more rarely,
      the autosomal recessive hypercholesterolemia adaptor protein, may lead to a
      similar phenotype with varying severity. HoFH patients have aggressive
      cardiovascular disease that develops from birth due to severe LDLR defects,
      resulting, in turn, in excess production of Apo B-containing atherogenic
      lipoproteins (low-density lipoprotein [LDL] and lipoprotein(a)). The condition is
      characterized by exceptionally high LDL cholesterol levels, cutaneous and tendon
      xanthomas, and valvular and supravalvular stenosis, and accelerated
      atherosclerosis often manifests in the first 2 decades of life. Treatment
      typically involves lipid-modifying medical therapy as well as mechanical removal
      of plasma LDL by means of apheresis. Although statins have afforded survival into
      the third and fourth decades of life, further therapeutic advancements currently
      under investigation promise hope of further improvements in survival and improved
      quality of life. The purpose of this review is to provide current perspectives on
      diagnosis and therapy in an effort to encourage early recognition and treatment
      of this rare but severe disease.

PMID- 22398275
TI  - Enhancer of polycomb1 lessens neointima formation by potentiation of myocardin
      induced smooth muscle differentiation.
AB  - OBJECTIVE: Previously, we reported that enhancer of polycomb1 (Epc1) induces
      skeletal muscle differentiation through the serum response factor (SRF).
      Considering that SRF plays a critical role in vascular smooth muscle cell (VSMC)
      differentiation, we expected that Epc1 also works in VSMCs. Here we examined the
      effect of Epc1 on neointima formation after arterial balloon injury and the
      underlying mechanism. METHODS: Epc1 expression was examined in carotid artery
      injury or VSMC models. Interaction with myocardin (Myocd), a master regulator of
      smooth muscle differentiation, was examined by immunoprecipitation or promoter
      analysis with smooth muscle (SM) 22alpha promoter. Finally, we investigated
      whether local delivery of Epc1 regulated neointimal formation after injury.
      RESULTS: Epc1 expression was down-regulated during proliferation induced by
      platelet-derived growth factor BB, whereas it was upregulated during
      differentiation in VSMCs. Forced expression of Epc1 induced VSMC differentiation.
      Epc1 physically interacted with Myocd to synergistically activate SM22alpha
      promoter activity. Transient transfection of Epc1 enhanced the physical
      interaction between Myocd and SRF, whereas that interaction was reduced when A10
      cells were treated with siRNA for Epc1. Local delivery of Epc1 significantly
      reduced neointima formation induced by balloon injury. CONCLUSIONS: Our results
      indicate that Epc1 induces VSMC differentiation by interacting with Myocd to
      induce SRF-dependent smooth muscle genes. We propose that Epc1 acts as a novel
      negative regulator of neointima formation after carotid injury.

PMID- 22398276
TI  - Identification of genes affecting apolipoprotein B secretion following siRNA
      mediated gene knockdown in primary human hepatocytes.
AB  - OBJECTIVE: Genome-wide association studies (GWAS) are useful in studying the
      complex pathways underlying diseases such as atherosclerosis; however, additional
      testing is often necessary to identify the disease causal genes linked to GWAS
      loci. We used siRNA-mediated gene knockdown in primary human hepatocytes (PHuH)
      to identify potential GWAS causal genes affecting the hepatic secretion of
      apolipoprotein B (ApoB), ApoA1, and proprotein convertase subtilisin/kexin type
      9. MATERIALS AND METHODS: Candidate causal genes within GWAS loci affecting human
      plasma levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, and
      triglycerides were identified from the literature; 191 genes were selected from
      74 loci. A functional siRNA screen was performed using PHuH. RESULTS: Four genes:
      poly (ADP-ribose) polymerases member 10, haptoglobin, fucosyltransferase 1, and
      lysophosphatidic acid receptor 2 were identified and confirmed. Knocking down
      these genes reduced cell-associated and secreted ApoB levels. CONCLUSION:
      Modification of these four genes may affect plasma lipids through modulation of
      ApoB secretion.

PMID- 22398277
TI  - Developmental change of visuo-spatial working memory in children: quantitative
      evaluation through an Advanced Trail Making Test.
AB  - AIM: The present study aimed to investigate the developmental change in Visuo
      Spatial Working Memory (VSWM) in typically developed children using a specially
      designed Advanced Trail Making Test for children (ATMT-C). METHODS: We developed
      a new method for evaluating VSWM efficiency in children using a modified version
      ATMT to suit their shorter sustained attention. The ATMT-C consists of two parts;
      a number-based ATMT and a hiragana (Japanese phonogram)-based ATMT, both
      employing symbols familiar to young children. A total of 94 healthy participants
      (6-28 years of age) were enrolled in this study. RESULTS: A non-linear
      developmental change of VSWM efficiency was observed in the results from the ATMT
      C. In the number-based ATMT, children under 8 years of age showed a relatively
      rapid increase in VSWM efficiency while older children (9-12 years) had a more
      gradual increase in VSWM efficiency. Results from the hiragana-based ATMT-C
      showed a slightly delayed increase pattern in VSWM efficiency compared to the
      pattern from the number-based ATMT. There were no significant differences in VSWM
      efficiency for gender, handedness and test order. INTERPRETATION: VSWM in
      children gradually matures in a non steady-state manner and there is an important
      stage for VSWM maturation before reaching 12 years of age. VSWM efficiency may
      also vary depending on developmental condition of its cognitive subsystems.

PMID- 22398278
TI  - Thrombophilia among Chinese women with venous thromboembolism during pregnancy.
AB  - AIMS: To assess the prevalence of thrombophilia among Chinese women with venous
      thromboembolism (VTE) developed during pregnancy. METHODS: Based on information
      from a tertiary teaching unit, all recorded cases of deep vein thrombosis (DVT)
      and pulmonary embolism (PE) during pregnancy diagnosed between 1997 and 2005,
      were assessed for prevalence of thrombophilia. Fifty-five healthy women, who had
      at least one normal pregnancy but without any previous history of VTE, were
      recruited as controls. RESULTS: A total of 44 subjects completed thrombophilia
      screening, of whom 5 (11%) were confirmed to have thrombophilia [protein C (PC)
      deficiency (2), protein S (PS) deficiency (1), combined PC & PS deficiency (1)
      and antithrombin III deficiency (1)]. Homozygous 5,10-methylenetetrahydrofolate
      reductase (C677T) gene mutation was found in 6 (14%) subjects but not in the
      controls. There was no antiphospholipid syndrome, activated PC resistance, factor
      V Leiden or prothrombin gene mutations. CONCLUSION: In the Chinese population, PS
      and PC deficiencies are common thrombophilia for VTE during pregnancy and
      thrombophilia screening should be recommended in all pregnant women who suffer
      from VTE.

PMID- 22398279
TI  - Anti-tetherin activities of HIV-1 Vpu and Ebola virus glycoprotein do not involve
      removal of tetherin from lipid rafts.
AB  - BST-2/tetherin is an interferon-inducible host restriction factor that blocks the
      release of newly formed enveloped viruses. It is enriched in lipid raft membrane
      microdomains, which are also the sites of assembly of several enveloped viruses.
      Viral anti-tetherin factors, such as the HIV-1 Vpu protein, typically act by
      removing tetherin from the cell surface. In contrast, the Ebola virus
      glycoprotein (GP) is unusual in that it blocks tetherin restriction without
      apparently altering its cell surface localization. We explored the possibility
      that GP acts to exclude tetherin from the specific sites of virus assembly
      without overtly removing it from the cell surface and that lipid raft exclusion
      is the mechanism involved. However, we found that neither GP nor Vpu had any
      effect on tetherin's distribution within lipid raft domains. Furthermore, GP did
      not prevent the colocalization of tetherin and budding viral particles. Contrary
      to previous reports, we also found no evidence that GP is itself a raft protein.
      Together, our data indicate that the exclusion of tetherin from lipid rafts is
      not the mechanism used by either HIV-1 Vpu or Ebola virus GP to counteract
      tetherin restriction.

PMID- 22398280
TI  - TNPO3 is required for HIV-1 replication after nuclear import but prior to
      integration and binds the HIV-1 core.
AB  - TNPO3 is a nuclear importer required for HIV-1 infection. Here, we show that
      depletion of TNPO3 leads to an HIV-1 block after nuclear import but prior to
      integration. To investigate the mechanistic requirement of TNPO3 in HIV-1
      infection, we tested the binding of TNPO3 to the HIV-1 core and found that TNPO3
      binds to the HIV-1 core. Overall, this work suggests that TNPO3 interacts with
      the incoming HIV-1 core in the cytoplasm to assist a process that is important
      for HIV-1 infection after nuclear import.

PMID- 22398281
TI  - Generation of an HIV-1-resistant immune system with CD34(+) hematopoietic stem
      cells transduced with a triple-combination anti-HIV lentiviral vector.
AB  - HIV gene therapy has the potential to offer an alternative to the use of current
      small-molecule antiretroviral drugs as a treatment strategy for HIV-infected
      individuals. Therapies designed to administer HIV-resistant stem cells to an
      infected patient may also provide a functional cure, as observed in a bone marrow
      transplant performed with hematopoietic stem cells (HSCs) homozygous for the CCR5
      Delta32-bp allele. In our current studies, preclinical evaluation of a
      combination anti-HIV lentiviral vector was performed, in vivo, in humanized NOD
      RAG1(-/-) IL2rgamma(-/-) knockout mice. This combination vector, which displays
      strong preintegration inhibition of HIV-1 infection in vitro, contains a
      human/rhesus macaque TRIM5alpha isoform, a CCR5 short hairpin RNA (shRNA), and a
      TAR decoy. Multilineage hematopoiesis from anti-HIV lentiviral vector-transduced
      human CD34(+) HSCs was observed in the peripheral blood and in various lymphoid
      organs, including the thymus, spleen, and bone marrow, of engrafted mice. Anti
      HIV vector-transduced CD34(+) cells displayed normal development of immune cells,
      including T cells, B cells, and macrophages. The anti-HIV vector-transduced cells
      also displayed knockdown of cell surface CCR5 due to the expression of the CCR5
      shRNA. After in vivo challenge with either an R5-tropic BaL-1 or X4-tropic NL4-3
      strain of HIV-1, maintenance of human CD4(+) cell levels and a selective survival
      advantage of anti-HIV gene-modified cells were observed in engrafted mice. The
      data provided from our study confirm the safety and efficacy of this combination
      anti-HIV lentiviral vector in a hematopoietic stem cell gene therapy setting for
      HIV and validates its potential application in future clinical trials.

PMID- 22398282
TI  - Plasticity and virus specificity of the airway epithelial cell immune response
      during respiratory virus infection.
AB  - Airway epithelial cells (AECs) provide the first line of defense in the
      respiratory tract and are the main target of respiratory viruses. Here, using
      oligonucleotide and protein arrays, we analyze the infection of primary polarized
      human AEC cultures with influenza virus and respiratory syncytial virus (RSV),
      and we show that the immune response of AECs is quantitatively and qualitatively
      virus specific. Differentially expressed genes (DEGs) specifically induced by
      influenza virus and not by RSV included those encoding interferon B1 (IFN-B1),
      type III interferons (interleukin 28A [IL-28A], IL-28B, and IL-29), interleukins
      (IL-6, IL-1A, IL-1B, IL-23A, IL-17C, and IL-32), and chemokines (CCL2, CCL8, and
      CXCL5). Lack of type I interferon or STAT1 signaling decreased the expression and
      secretion of cytokines and chemokines by the airway epithelium. We also observed
      strong basolateral polarization of the secretion of cytokines and chemokines by
      human and murine AECs during infection. Importantly, the antiviral response of
      human AECs to influenza virus or to RSV correlated with the infection signature
      obtained from peripheral blood mononuclear cells (PBMCs) isolated from patients
      with acute influenza or RSV bronchiolitis, respectively. IFI27 (also known as
      ISG12) was identified as a biomarker of respiratory virus infection in both AECs
      and PBMCs. In addition, the extent of the transcriptional perturbation in PBMCs
      correlated with the clinical disease severity. Our results demonstrate that the
      human airway epithelium mounts virus-specific immune responses that are likely to
      determine the subsequent systemic immune responses and suggest that the absence
      of epithelial immune mediators after RSV infection may contribute to explaining
      the inadequacy of systemic immunity to the virus.

PMID- 22398283
TI  - Influenza virus sequence feature variant type analysis: evidence of a role for
      NS1 in influenza virus host range restriction.
AB  - Genetic drift of influenza virus genomic sequences occurs through the combined
      effects of sequence alterations introduced by a low-fidelity polymerase and the
      varying selective pressures experienced as the virus migrates through different
      host environments. While traditional phylogenetic analysis is useful in tracking
      the evolutionary heritage of these viruses, the specific genetic determinants
      that dictate important phenotypic characteristics are often difficult to discern
      within the complex genetic background arising through evolution. Here we describe
      a novel influenza virus sequence feature variant type (Flu-SFVT) approach, made
      available through the public Influenza Research Database resource
      (www.fludb.org), in which variant types (VTs) identified in defined influenza
      virus protein sequence features (SFs) are used for genotype-phenotype association
      studies. Since SFs have been defined for all influenza virus proteins based on
      known structural, functional, and immune epitope recognition properties, the Flu
      SFVT approach allows the rapid identification of the molecular genetic
      determinants of important influenza virus characteristics and their connection to
      underlying biological functions. We demonstrate the use of the SFVT approach to
      obtain statistical evidence for effects of NS1 protein sequence variations in
      dictating influenza virus host range restriction.

PMID- 22398284
TI  - Recombinant influenza A viruses with enhanced levels of PB1 and PA viral protein
      expression.
AB  - Influenza A viruses containing the promoter mutations G3A/C8U in a given segment
      express increased levels of the corresponding viral protein during infection due
      to increased levels of mRNA or cRNA species. The replication of these recombinant
      viruses is attenuated, and they have an enhanced shedding of noninfectious
      particles and are incapable of antagonizing interferon (IFN) effectively. Our
      findings highlight the possibility of increasing influenza virus protein
      expression and the need for a delicate balance between influenza viral
      replication, protein expression, and assembly.

PMID- 22398285
TI  - Superinfection exclusion is an active virus-controlled function that requires a
      specific viral protein.
AB  - Superinfection exclusion, a phenomenon in which a preexisting viral infection
      prevents a secondary infection with the same or a closely related virus, has been
      described for various viruses, including important pathogens of humans, animals,
      and plants. The phenomenon was initially used to test the relatedness of plant
      viruses. Subsequently, purposeful infection with a mild isolate has been
      implemented as a protective measure against virus isolates that cause severe
      disease. In the medical and veterinary fields, superinfection exclusion was found
      to interfere with repeated applications of virus-based vaccines to individuals
      with persistent infections and with the introduction of multicomponent vaccines.
      In spite of its significance, our understanding of this phenomenon is
      surprisingly incomplete. Recently, it was demonstrated that superinfection
      exclusion of Citrus tristeza virus (CTV), a positive-sense RNA closterovirus,
      occurs only between isolates of the same strain, but not between isolates of
      different strains of the virus. In this study, I show that superinfection
      exclusion by CTV requires production of a specific viral protein, the p33
      protein. Lack of the functional p33 protein completely eliminated the ability of
      the virus to exclude superinfection by the same or a closely related virus.
      Remarkably, the protein appeared to function only in a homology-dependent manner.
      A cognate protein from a heterologous strain failed to confer the exclusion,
      suggesting the existence of precise interactions of the p33 protein with other
      factors involved in this complex phenomenon.

PMID- 22398286
TI  - Mouse prion protein (PrP) segment 100 to 104 regulates conversion of PrP(C) to
      PrP(Sc) in prion-infected neuroblastoma cells.
AB  - Prion diseases are characterized by the replicative propagation of disease
      associated forms of prion protein (PrP(Sc); PrP refers to prion protein). The
      propagation is believed to proceed via two steps; the initial binding of the
      normal form of PrP (PrP(C)) to PrP(Sc) and the subsequent conversion of PrP(C) to
      PrP(Sc). We have explored the two-step model in prion-infected mouse
      neuroblastoma (ScN2a) cells by focusing on the mouse PrP (MoPrP) segment 92
      GGTHNQWNKPSKPKTN-107, which is within a region previously suggested to be part of
      the binding interface or shown to differ in its accessibility to anti-PrP
      antibodies between PrP(C) and PrP(Sc). Exchanging the MoPrP segment with the
      corresponding chicken PrP segment (106-GGSYHNQKPWKPPKTN-121) revealed the
      necessity of MoPrP residues 99 to 104 for the chimeras to achieve the PrP(Sc)
      state, while segment 95 to 98 was replaceable with the chicken sequence. An
      alanine substitution at position 100, 102, 103, or 104 of MoPrP gave rise to
      nonconvertible mutants that associated with MoPrP(Sc) and interfered with the
      conversion of endogenous MoPrP(C). The interference was not evoked by a chimera
      (designated MCM2) in which MoPrP segment 95 to 104 was changed to the chicken
      sequence, though MCM2 associated with MoPrP(Sc). Incubation of the cells with a
      synthetic peptide composed of MoPrP residues 93 to 107 or alanine-substituted
      cognates did not inhibit the conversion, whereas an anti-P8 antibody recognizing
      the above sequence in PrP(C) reduced the accumulation of PrP(Sc) after 10 days of
      incubation of the cells. These results suggest the segment 100 to 104 of MoPrP(C)
      plays a key role in conversion after binding to MoPrP(Sc).

PMID- 22398287
TI  - Influenza viruses expressing chimeric hemagglutinins: globular head and stalk
      domains derived from different subtypes.
AB  - The influenza virus hemagglutinin molecule possesses a globular head domain that
      mediates receptor binding and a stalk domain at the membrane-proximal region. We
      generated functional influenza viruses expressing chimeric hemagglutinins
      encompassing a variety of globular head and stalk combinations, not only from
      different hemagglutinin subtypes but also from different hemagglutinin
      phylogenetic groups. These chimeric recombinant viruses possess growth properties
      similar to those of wild-type influenza viruses and can be used as reagents to
      measure domain-specific antibodies in virological and immunological assays.

PMID- 22398288
TI  - Vaccinia virus A6 is essential for virion membrane biogenesis and localization of
      virion membrane proteins to sites of virion assembly.
AB  - Poxvirus acquires its primary envelope through a process that is distinct from
      those of other enveloped viruses. The molecular mechanism of this process is
      poorly understood, but several poxvirus proteins essential for the process have
      been identified in studies of vaccinia virus (VACV), the prototypical poxvirus.
      Previously, we identified VACV A6 as an essential factor for virion morphogenesis
      by studying a temperature-sensitive mutant with a lesion in A6. Here, we further
      studied A6 by constructing and characterizing an inducible virus (iA6) that could
      more stringently repress A6 expression. When A6 expression was induced by the
      inducer isopropyl-beta-D-thiogalactoside (IPTG), iA6 replicated normally, and
      membrane proteins of mature virions (MVs) predominantly localized in viral
      factories where virions were assembled. However, when A6 expression was
      repressed, electron microscopy of infected cells showed the accumulation of large
      viroplasm inclusions containing virion core proteins but no viral membranes.
      Immunofluorescence and cell fractionation studies showed that the major MV
      membrane proteins A13, A14, D8, and H3 did not localize to viral factories but
      instead accumulated in the secretory compartments, including the endoplasmic
      reticulum. Overall, our results show that A6 is an additional VACV protein that
      participates in an early step of virion membrane biogenesis. Furthermore, A6 is
      required for MV membrane protein localization to sites of virion assembly,
      suggesting that MV membrane proteins or precursors of MV membranes are trafficked
      to sites of virion assembly through an active, virus-mediated process that
      requires A6.

PMID- 22398290
TI  - Adaptation of a genotype 3 hepatitis E virus to efficient growth in cell culture
      depends on an inserted human gene segment acquired by recombination.
AB  - An infectious cDNA clone of a genotype 3 strain of hepatitis E virus adapted to
      growth in HepG2/C3A human hepatoma cells was constructed. This virus was unusual
      in that the hypervariable region of the adapted virus contained a 171-nucleotide
      insertion that encoded 58 amino acids of human S17 ribosomal protein. Analyses of
      virus from six serial passages indicated that genomes with this insert, although
      initially rare, were selected during the first passage, suggesting it conferred a
      significant growth advantage. RNA transcripts from this cDNA and the viruses
      encoded by them were infectious for cells of both human and swine origin, the
      major host species for this zoonotic virus. Mutagenesis studies demonstrated that
      the S17 insert was a major factor in cell culture adaptation. Introduction of 54
      synonymous mutations into the insert had no detectable effect, thus implicating
      protein, rather than RNA, as the important component. Truncation of the insert by
      50% decreased the levels of successful transfection by ~3-fold. Substitution of
      the S17 sequence by a different ribosomal protein sequence or by GTPase
      activating protein sequence resulted in a partial enhancement of transfection
      levels, whereas substitution with 58 amino acids of green fluorescent protein had
      no effect. Therefore, both the sequence length and the amino acid composition of
      the insert were important. The S17 sequence did not affect transfection of human
      hepatoma cells when inserted into the hypervariable region of a genotype 1
      strain, but this chimeric genome acquired a dramatic ability to replicate in
      hamster cells.

PMID- 22398289
TI  - SUMO binding by the Epstein-Barr virus protein kinase BGLF4 is crucial for BGLF4
      function.
AB  - An Epstein-Barr virus (EBV) protein microarray was used to screen for proteins
      binding noncovalently to the small ubiquitin-like modifier SUMO2. Among the 11
      SUMO binding proteins identified was the conserved protein kinase BGLF4. The
      mutation of potential SUMO interaction motifs (SIMs) in BGLF4 identified N- and C
      terminal SIMs. The mutation of both SIMs changed the intracellular localization
      of BGLF4 from nuclear to cytoplasmic, while BGLF4 mutated in the N-terminal SIM
      remained predominantly nuclear. The mutation of the C-terminal SIM yielded an
      intermediate phenotype with nuclear and cytoplasmic staining. The transfer of
      BGLF4 amino acids 342 to 359 to a nuclear green fluorescent protein (GFP)-tagged
      reporter protein led to the relocalization of the reporter to the cytoplasm.
      Thus, the C-terminal SIM lies adjacent to a nuclear export signal, and
      coordinated SUMO binding by the N- and C-terminal SIMs blocks export and allows
      the nuclear accumulation of BGLF4. The mutation of either SIM prevented SUMO
      binding in vitro. The ability of BGLF4 to abolish the SUMOylation of the EBV
      lytic cycle transactivator ZTA was dependent on both BGLF4 SUMO binding and BGLF4
      kinase activity. The global profile of SUMOylated cell proteins was also
      suppressed by BGLF4 but not by the SIM or kinase-dead BGLF4 mutant. The effective
      BGLF4-mediated dispersion of promyelocytic leukemia (PML) bodies was dependent on
      SUMO binding. The SUMO binding function of BGLF4 was also required to induce the
      cellular DNA damage response and to enhance the production of extracellular virus
      during EBV lytic replication. Thus, SUMO binding by BGLF4 modulates BGLF4
      function and affects the efficiency of lytic EBV replication.

PMID- 22398291
TI  - Attenuated influenza virus construct with enhanced hemagglutinin protein
      expression.
AB  - Influenza A viruses encoding an altered viral NS1 protein have emerged as
      promising live attenuated vaccine platforms. A carboxy-terminal truncation in the
      NS1 protein compromises its interferon antagonism activity, making these viruses
      attenuated in the host yet still able to induce protection from challenge with
      wild-type viruses. However, specific viral protein expression by NS1-truncated
      viruses is known to be decreased in infected cells. In this report, we show that
      recombinant H5N1 and H1N1 influenza viruses encoding a truncated NS1 protein
      expressed lower levels of hemagglutinin (HA) protein in infected cells than did
      wild-type viruses. This reduction in HA protein expression correlated with a
      reduction in HA mRNA levels in infected cells. NS1 truncation affected the
      expression of HA protein but not that of the nucleoprotein (NP). This segment
      specificity was mapped to the terminal sequences of their specific viral RNAs.
      Since the HA protein is the major immunogenic component in influenza virus
      vaccines, we sought to restore its expression levels in NS1-truncated viruses in
      order to improve their vaccine efficacy. For this purpose, we generated an NS1
      truncated recombinant influenza A/Puerto Rico/8/34 (rPR8) virus carrying the G3A
      C8U "superpromoter" mutations in the HA genomic RNA segment. This strategy
      retained the attenuation properties of the recombinant virus but enhanced the
      expression level of HA protein in infected cells. Finally, mice immunized with
      rPR8 viruses encoding a truncated NS1 protein and carrying the G3A C8U mutations
      in the HA segment demonstrated enhanced protection from wild-type virus challenge
      over that for mice vaccinated with an rPR8 virus encoding the truncated NS1
      protein alone.

PMID- 22398292
TI  - Shelterin dysfunction and p16(INK4a)-mediated growth inhibition in HIV-1-specific
      CD8 T cells.
AB  - HIV-1-specific cytotoxic T cell responses are expanded during advanced HIV-1
      infection but seem unable to effectively protect the host against disease
      progression. These cells are able to produce gamma interferon and remain
      metabolically active but have defective proliferative activities, shortened
      telomeric DNA, and other signs of accelerated aging. To investigate the molecular
      mechanisms underlying the premature senescence of HIV-1-specific T cells, we
      focused here on the expression and function of a group of six nucleoproteins that
      are responsible for protecting and maintaining the structural integrity of
      telomeric DNA and are commonly referred to as "shelterin." We show that in
      progressive HIV-1 infection, the two major shelterin components TRF2 and TPP1 are
      selectively reduced in HIV-1-specific CD8 T cells, but not in T cells recognizing
      alternative viral species. This coincided with increased recruitment of 53BP1, a
      prominent DNA damage response factor, to telomeric DNA sites and was associated
      with elevated expression of the tumor suppressor p16(INK4a), which causes
      cellular growth inhibition in response to structural DNA damage. Notably,
      defective shelterin function and upregulation of p16(INK4a) remained unaffected
      by experimental blockade of PD-1, indicating a possibly irreversible structural
      defect in HIV-1-specific CD8 T cells in progressors that cannot be overcome by
      manipulation of inhibitory cell-signaling pathways. These data suggest that
      shelterin dysfunction and ensuing upregulation of the tumor suppressor p16(INK4a)
      promote accelerated aging of HIV-1-specific T cells during progressive HIV-1
      infection.

PMID- 22398293
TI  - The myristate moiety and amino terminus of vaccinia virus l1 constitute a
      bipartite functional region needed for entry.
AB  - Vaccinia virus (VACV) L1 is a myristoylated envelope protein which is required
      for cell entry and the fusion of infected cells. L1 associates with members of
      the entry-fusion complex (EFC), but its specific role in entry has not been
      delineated. We recently demonstrated (Foo CH, et al., Virology 385:368-382, 2009)
      that soluble L1 binds to cells and blocks entry, suggesting that L1 serves as the
      receptor-binding protein for entry. Our goal is to identify the structural
      domains of L1 which are essential for its functions in VACV entry. We
      hypothesized that the myristate and the conserved residues at the N terminus of
      L1 are critical for entry. To test our hypothesis, we generated mutants in the N
      terminus of L1 and used a complementation assay to evaluate their ability to
      rescue infectivity. We also assessed the myristoylation efficiency of the mutants
      and their ability to interact with the EFC. We found that the N terminus of L1
      constitutes a region that is critical for the infectivity of VACV and for
      myristoylation. At the same time, the nonmyristoylated mutants were incorporated
      into mature virions, suggesting that the myristate is not required for the
      association of L1 with the viral membrane. Although some of the mutants exhibited
      altered structural conformations, two mutants with impaired infectivity were
      similar in conformation to wild-type L1. Importantly, these two mutants, with
      changes at A4 and A5, undergo myristoylation. Overall, our results imply dual
      differential roles for myristate and the amino acids at the N terminus of L1. We
      propose a myristoyl switch model to describe how L1 functions.

PMID- 22398295
TI  - Structure of the Fab-labeled "breathing" state of native poliovirus.
AB  - At 37 degrees C, the structure of poliovirus is dynamic, and internal
      polypeptides VP4 and N terminus of VP1 (residues 1 to 53) externalize reversibly.
      An Fab fragment of a monospecific antibody, which binds to residues 39 to 55 of
      VP1, was utilized to locate the N termini of VP1 in native (160S) particles in
      this "breathing" state. Fab and virus were mixed and imaged via cryogenic
      electron microscopy. The resulting reconstruction showed the capsid expands
      similarly to the irreversibly altered cell entry intermediate (135S) particle,
      but the N terminus of VP1 is located near the 2-fold axes, instead of the
      "propeller tip" as in 135S particles.

PMID- 22398294
TI  - Isolation and characterization of a novel Betacoronavirus subgroup A coronavirus,
      rabbit coronavirus HKU14, from domestic rabbits.
AB  - We describe the isolation and characterization of a novel Betacoronavirus
      subgroup A coronavirus, rabbit coronavirus HKU14 (RbCoV HKU14), from domestic
      rabbits. The virus was detected in 11 (8.1%) of 136 rabbit fecal samples by
      reverse transcriptase PCR (RT-PCR), with a viral load of up to 10(8) copies/ml.
      RbCoV HKU14 was able to replicate in HRT-18G and RK13 cells with cytopathic
      effects. Northern blotting confirmed the production of subgenomic mRNAs coding
      for the HE, S, NS5a, E, M, and N proteins. Subgenomic mRNA analysis revealed a
      transcription regulatory sequence, 5'-UCUAAAC-3'. Phylogenetic analysis showed
      that RbCoV HKU14 formed a distinct branch among Betacoronavirus subgroup A
      coronaviruses, being most closely related to but separate from the species
      Betacoronavirus 1. A comparison of the conserved replicase domains showed that
      RbCoV HKU14 possessed <90% amino acid identities to most members of
      Betacoronavirus 1 in ADP-ribose 1"-phosphatase (ADRP) and nidoviral uridylate
      specific endoribonuclease (NendoU), indicating that RbCoV HKU14 should represent
      a separate species. RbCoV HKU14 also possessed genomic features distinct from
      those of other Betacoronavirus subgroup A coronaviruses, including a unique NS2a
      region with a variable number of small open reading frames (ORFs). Recombination
      analysis revealed possible recombination events during the evolution of RbCoV
      HKU14 and members of Betacoronavirus 1, which may have occurred during cross
      species transmission. Molecular clock analysis using RNA-dependent RNA polymerase
      (RdRp) genes dated the most recent common ancestor of RbCoV HKU14 to around 2002,
      suggesting that this virus has emerged relatively recently. Antibody against
      RbCoV was detected in 20 (67%) of 30 rabbit sera tested by an N-protein-based
      Western blot assay, whereas neutralizing antibody was detected in 1 of these 20
      rabbits.

PMID- 22398296
TI  - Development of an insect vector cell culture and RNA interference system to
      investigate the functional role of fijivirus replication protein.
AB  - An in vitro culture system of primary cells from white-backed planthopper, an
      insect vector of Southern rice black-streaked dwarf virus (SRBSDV), a fijivirus,
      was established to study replication of the virus. Viroplasms, putative sites of
      viral replication, contained the nonstructural viral protein P9-1, viral RNA,
      outer-capsid proteins, and viral particles in virus-infected cultured insect
      vector cells, as revealed by transmission electron and confocal microscopy.
      Formation of viroplasm-like structures in non-host insect cells upon expression
      of P9-1 suggested that the matrix of viroplasms observed in virus-infected cells
      was composed basically of P9-1. In cultured insect vector cells, knockdown of P9
      1 expression due to RNA interference (RNAi) induced by synthesized double
      stranded RNA (dsRNA) from the P9-1 gene strongly inhibited viroplasm formation
      and viral infection. RNAi induced by ingestion of dsRNA strongly abolished
      viroplasm formation, preventing efficient viral spread in the body of intact
      vector insects. All these results demonstrated that P9-1 was essential for
      viroplasm formation and viral replication. This system, combining insect vector
      cell culture and RNA interference, can further advance our understanding of the
      biological activities of fijivirus replication proteins.

PMID- 22398297
TI  - Elevated amygdala activity to negative faces in young adults with early onset
      major depressive disorder.
AB  - Abnormalities in amygdala activity have been implicated in adolescents and older
      adults with major depressive disorder (MDD), but few studies have focused on
      young adults with early-onset MDD. In this study, we measured amygdala activity
      in 27 young adults with early-onset MDD and 25 healthy controls (HC) using
      functional magnetic resonance imaging (fMRI) with an emotional processing task.
      Both groups showed significant bilateral activation within the amygdala to threat
      related facial expressions. In the matching face task, the activations of the
      left amygdala, thalamus, prefrontal and temporal cortex were significantly
      greater while the activation of the right prefrontal was significantly lower for
      the MDD group compared with the HC group. For the MDD group, there was a
      significant positive correlation between the activity of the amygdala and scores
      on the Chinese version of the Center for Epidemiologic Studies Depression Scale.
      Overall, our findings suggest that young adults with early-onset MDD may be
      characterized by abnormalities in nodes along the fronto-limbic pathways when
      facing threat-related facial expression.

PMID- 22398298
TI  - Tract-specific analysis of white matter integrity disruption in schizophrenia.
AB  - Several studies have suggested that white matter integrity is disrupted in some
      brain regions in patients with schizophrenia. The purpose of this study was to
      assess the white matter integrity of the cingulum, uncinate fasciculus, fornix,
      and corpus callosum using diffusion tensor imaging (DTI). Participants comprised
      39 patients with schizophrenia (19 males and 20 females) and 40 age-matched
      normal controls (20 males and 20 females). We quantitatively assessed the
      fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the
      anterior cingulum, body of the cingulum, uncinate fasciculus, fornix, and corpus
      callosum on a tract-specific basis using diffusion tensor tractography (DTT).
      Group differences in FA and ADC between the patients and normal controls were
      sought. Additional exploratory analyses of the relationship between the FA or ADC
      and four clinical parameters (i.e., illness duration, positive symptom scores,
      negative symptom scores, and medication dosage) were performed. Results were
      analyzed in gender-combined and gender-separated group comparisons. FA was
      significantly lower on both sides of the anterior cingulum, uncinate fasciculus,
      and fornix in the schizophrenia patients irrespective of gender group separation.
      In the gender-combined analyses, significantly higher ADC values were
      demonstrated in the schizophrenia patients in both sides of the anterior
      cingulum, body of the cingulum and uncinate fasciculus, the left fornix, and the
      corpus callosum, compared with those of the normal controls. In the gender
      separated analyses, the male patients showed higher ADC in the left anterior
      cingulum, the bilateral cingulum bodies, and the bilateral uncinate fasciculi.
      The female patients showed higher ADC in the right anterior cingulum, the left
      fornix, and the bilateral uncinate fasciculus. In correlation analyses, a
      significant negative correlation was found between illness duration and ADC in
      the right anterior cingulum in the gender-combined analyses. The gender-separated
      analyses found that the male patients had a significant negative correlation
      between negative symptom scores and FA in the right fornix, a positive
      correlation between illness duration and FA in the right anterior cingulum, and a
      negative correlation between illness duration and FA in the left uncinate
      fasciculus. Our DTI study showed that the integrity of white matter is disrupted
      in patients with schizophrenia. The results of our sub-analyses suggest that
      changes in FA and ADC may be related to negative symptom scores or illness
      duration.

PMID- 22398299
TI  - Brain activation during the perception of stressful word stimuli concerning
      interpersonal relationships in anorexia nervosa patients with high degrees of
      alexithymia in an fMRI paradigm.
AB  - Several studies have reported that anorexia nervosa (AN) patients have high
      levels of alexithymia. However, relatively little is known about the underlying
      neurobiological relationships between alexithymia and AN. We used functional
      magnetic resonance imaging to examine the brain responses in 30 AN patients and
      20 healthy women during the processing of negative words concerning interpersonal
      relationships. We investigated the relationship between alexithymia levels and
      brain activation in AN. AN patients showed significant activation of the
      orbitofrontal cortex, dorsolateral prefrontal cortex and medial prefrontal cortex
      while processing negative words concerning interpersonal relationships, as
      compared to the processing of neutral words. Moreover, the subjective rating of
      unpleasantness with negative words and neural activities in the amygdala,
      posterior cingulate cortex (PCC) and anterior cingulate cortex (ACC) negatively
      correlated with the level of alexithymia in AN. Our neuroimaging results suggest
      that AN patients tend to cognitively process negative words concerning
      interpersonal relationships, resulting in activation of the prefrontal cortex.
      Lower activation of the amygdala, PCC and ACC in response to these words may
      contribute to the impairments of emotional processing that are hallmarks of
      alexithymia. Functional abnormalities associated with alexithymia may be involved
      in the emotional processing impairments in AN patients.

PMID- 22398301
TI  - Challenges in the evaluation for possible abuse: presentations of congenital
      bleeding disorders in childhood.
AB  - OBJECTIVES: To describe children with congenital bleeding disorders that present
      in a manner that may be concerning for non-accidental trauma (NAT), and to
      evaluate associations with disease and demographic characteristics. METHODS: Ten
      year retrospective chart review of subjects at a Hemophilia Treatment Center.
      Demographic, historical, and disease characteristics were collected. Findings
      were compared to a priori criteria for bleeding/bruising that is concerning for
      abuse. RESULTS: Twenty-nine (15.3%) of the 189 children in the study had an
      initial presentation that was concerning for NAT. Of those 29, 75.9% were <5
      years of age, 44.8% had von Willebrand disease (vWD), 51.8% had hemophilia, and
      48.3% had a family history of a named bleeding disorder. Children from 9 months
      through 5 years of age were more likely than older children to present with
      findings concerning for abuse (OR 3.32, 1.21-9.10). No association was detected
      between presentation concerning for abuse and gender (OR 1.51, 0.6-3.77).
      Hemophilia was no more likely than vWD to present in a manner that was concerning
      for abuse (OR 0.7, 0.31-1.58). No children presented with patterned bruising.
      CONCLUSIONS: Children with bleeding disorders may present with bruising/bleeding
      that is clinically highly suggestive of NAT. PRACTICE IMPLICATIONS: Infants and
      young mobile children who have non-patterned bruising or bleeding as the only
      symptom concerning for abuse require an evaluation that includes testing for
      hemophilia and vWD. Children who have laboratory testing that indicates the
      presence of a bleeding disorder, but have clinical findings concerning for abuse,
      may benefit from a collaborative evaluation including a pediatric hematologist
      and a child abuse pediatrician.

PMID- 22398300
TI  - Experiential avoidance and the relationship between child maltreatment and PTSD
      symptoms: preliminary evidence.
AB  - OBJECTIVE: Not every adolescent exposed to child maltreatment develops symptoms
      of post-traumatic stress disorder (PTSD), emphasizing the need to identify
      variables that explain how some maltreated children come to develop these
      symptoms. This study tested whether a set of variables, respiratory sinus
      arrhythmia (RSA) and cortisol reactivity as well as experiential avoidance,
      explained the relationship between child maltreatment and PTSD symptoms. METHODS:
      Adolescent females (N=110; n=51 maltreated) 14-19 years of age completed
      interviews, questionnaires, and a stressor paradigm. A multiple mediator model
      was used to assess the effect for the set of variables while identifying specific
      indirect effects for each variable. RESULTS: Results indicated that the set of
      variables mediated the relationship between child maltreatment and PTSD symptoms.
      However, only experiential avoidance contributed significantly to this effect
      when simultaneously estimating all other variables. The indirect effect for
      experiential avoidance was also significantly stronger than the effects of RSA
      and cortisol reactivity. CONCLUSIONS: Data support the examination of
      experiential avoidance in understanding how adolescents who have been maltreated
      develop PTSD symptoms with implications for prevention and intervention.

PMID- 22398302
TI  - Epidemiology of abusive abdominal trauma hospitalizations in United States
      children.
AB  - OBJECTIVES: (1) To estimate the incidence of abusive abdominal trauma (AAT)
      hospitalizations among US children age 0-9 years. (2) To identify demographic
      characteristics of children at highest risk for AAT. DESIGN: Secondary data
      analysis of a cross-sectional, national hospitalization database. SETTING:
      Hospitalization data from the 2003 and 2006 Kids' Inpatient Database (KID). MAIN
      EXPOSURE: Frequency and rate of hospitalizations for abusive abdominal trauma as
      identified by ICD-9CM codes for abdominal trauma and child abuse and E-codes for
      inflicted injury. OUTCOME MEASURES: Hospitalization rates by age, insurance
      status, and frequency of specific organ injury. RESULTS: AAT rates were higher
      for infants than for any other age group, with 17.7 (95% CI 11.7-23.9) cases per
      million in 2006. More than 25% of all abdominal trauma in children <1 year of age
      was abusive. For all age groups, rates were higher for males than females, and
      for children insured by Medicaid compared to those with private insurance. Organs
      most commonly injured were the liver (64% of hospitalizations), kidney (19%), and
      stomach/intestines (12%). CONCLUSIONS: Although experts have considered toddlers
      to be at highest risk for AAT, infants have higher rates of AAT hospitalization.
      Similar to other abusive injuries, young age, male gender, and poverty are risk
      factors for AAT.

PMID- 22398303
TI  - Longitudinal study of self-regulation, positive parenting, and adjustment
      problems among physically abused children.
AB  - OBJECTIVE: Research using normative and high-risk samples indicates a significant
      link between problems with self-regulation and child maladjustment. Nevertheless,
      little is known about the processes that may modify the link between self
      regulation and maladjustment. This longitudinal study examined the joint
      contributions of child self-regulation and positive parenting behaviors to the
      development of externalizing and internalizing symptomatology spanning from
      preschool to 1st grade. METHODS: Data were collected on a total of 95 physically
      abused children (58% boys); our longitudinal analyses involved 43 children at
      Time 1 (preschool), 63 children at Time 2 (kindergarten), and 54 children at Time
      3 (1st grade). Children's self-regulation was measured by parent report, and
      their externalizing and internalizing symptomatology was evaluated by teachers.
      Parents completed self-report measures of positive parenting. RESULTS: Our
      structural equation modeling analyses revealed positive parenting as a protective
      factor that attenuated the concurrent association between low self-regulation and
      externalizing symptomatology among physically abused children. Our findings
      regarding longitudinal changes in children's externalizing symptomatology
      supported the differential susceptibility hypothesis: Physically abused children
      who were at greater risk due to low levels of self-regulation were more
      susceptible to the beneficial effects of positive parenting, compared to those
      with high levels of self-regulation. CONCLUSIONS: Findings suggest that although
      physical abuse presents formidable challenges that interfere with the development
      of adaptive self-regulation, positive parenting behaviors may ameliorate the
      detrimental effects of maladaptive self-regulation on the development of
      externalizing symptomatology. In addition, the positive and negative effects of
      caregiving behaviors were more prominent among physically abused children at
      great risk due to low self-regulation. PRACTICE IMPLICATIONS: Findings from the
      present study highlight the importance of attending to positive parenting
      behaviors and child self-regulation when working with physically abused children
      who are exhibiting externalizing symptomatology.

PMID- 22398304
TI  - A longitudinal examination of childhood maltreatment and adolescent obesity:
      results from the National Longitudinal Study of Adolescent Health (AddHealth)
      Study.
AB  - OBJECTIVES: We sought to explore the association between childhood maltreatment
      (e.g., neglect, physical and sexual abuse) and longitudinal growth trajectories
      of body mass index (BMI) from adolescence to young adulthood. METHODS: We used
      latent curve modeling to examine data from the National Longitudinal Study of
      Adolescent Health (N=8,471), pooling years 1995-2008. Relative weight was
      indicated by BMI. RESULTS: Children who experienced neglect had a faster average
      rate of BMI growth over time compared to children who experienced no childhood
      maltreatment. In addition, the co-occurrence of childhood neglect and physical
      abuse was related to increased levels of BMI at baseline, even after adjustment
      for 14 separate child and parental demographic and psychosocial characteristics.
      Parental obesity and education, child birth place, and family income were also
      associated with both baseline BMI and the rate of change in BMI over time.
      CONCLUSION: Childhood neglect plays a role in the development of adolescent
      obesity. Future research should examine potential mediators or moderators of the
      longitudinal relation between childhood neglect and adolescent and young adult
      obesity including impulsivity, depression, and compulsive eating behavior.

PMID- 22398305
TI  - Phthalates and perfluorooctanesulfonic acid in human amniotic fluid: temporal
      trends and timing of amniocentesis in pregnancy.
AB  - BACKGROUND: Measures of prenatal environmental exposures are important, and
      amniotic fluid levels may directly reflect fetal exposures during hypothesized
      windows of vulnerability. OBJECTIVES: We aimed to detect various phthalate
      metabolites and perfluorooctanesulfonic acid (PFOS) in human amniotic fluid, to
      study temporal exposure trends, and to estimate potential associations with
      gestational week of amniocentesis and maternal age and parity at amniocentesis.
      METHODS: We studied 300 randomly selected second-trimester amniotic fluid samples
      from a Danish pregnancy-screening biobank covering 1980 through 1996. We used
      only samples from male offspring pregnancies. We assayed the environmental
      pollutants by liquid chromatography/triple quadrupole mass spectrometry and
      analyzed data using generalized linear regression models. RESULTS: We detected
      the di(2-ethylhexyl) phthalate (DEHP) metabolite mono(2-ethyl-5-carboxypentyl)
      phthalate (5cx-MEPP) at a median concentration of 0.27 ng/mL [interquartile range
      (IQR): 0.20-0.37 ng/mL], the diisononyl phthalate (DiNP) metabolite mono(4-methyl
      7-carboxyheptyl) phthalate (7cx-MMeHP) at 0.07 ng/mL (IQR: 0.05-0.11 ng/mL), and
      PFOS at 1.1 ng/mL (IQR: 0.66-1.60 ng/mL). An increase of 1 calendar year was
      associated with 3.5% lower [95% confidence interval (CI): -4.8%, -2.1%] 5cx-MEPP
      levels and with 7.1% higher (95% CI: 5.3%, 9.0%) 7cx-MMeHP levels. For each later
      gestational week of amniocentesis, 5cx-MEPP was 9.9% higher (95% CI: 4.8%,
      15.2%), 7cx-MMeHP was 8.6% higher (95: CI: 2.7%, 14.9%), and PFOS was 9.4% higher
      (95: CI: 3.3%, 15.9%). We observed no associations with maternal age or parity.
      CONCLUSIONS: Measured metabolite levels appeared to parallel decreasing DEHP
      exposure and increasing DiNP exposure during the study period. The environmental
      pollutant levels were positively associated with later gestational age at
      amniocentesis during pregnancy weeks 12-22.

PMID- 22398306
TI  - Recent developments and applications of immobilized laccase.
AB  - Laccase is a promising biocatalyst with many possible applications, including
      bioremediation, chemical synthesis, biobleaching of paper pulp, biosensing,
      textile finishing and wine stabilization. The immobilization of enzymes offers
      several improvements for enzyme applications because the storage and operational
      stabilities are frequently enhanced. Moreover, the reusability of immobilized
      enzymes represents a great advantage compared with free enzymes. In this work, we
      discuss the different methodologies of enzyme immobilization that have been
      reported for laccases, such as adsorption, entrapment, encapsulation, covalent
      binding and self-immobilization. The applications of laccase immobilized by the
      aforementioned methodologies are presented, paying special attention to recent
      approaches regarding environmental applications and electrobiochemistry. 

PMID- 22398307
TI  - Pattern recognition receptors in immune disorders affecting the skin.
AB  - Pattern recognition receptors (PRRs) evolved to protect organisms against
      pathogens, but excessive signaling can induce immune responses that are harmful
      to the host. Putative PRR dysfunction is associated with numerous immune
      disorders that affect the skin, such as systemic lupus erythematosus, cryopyrin
      associated periodic syndrome, and primary inflammatory skin diseases including
      psoriasis and atopic dermatitis. As yet, the evidence is often confined to
      genetic association studies without additional proof of a causal relationship.
      However, insight into the role of PRRs in the pathophysiology of some disorders
      has already resulted in new therapeutic approaches based on immunomodulation of
      PRRs.

PMID- 22398308
TI  - Allergen-specific responses of CD19(+)CD5(+)Foxp3(+) regulatory B cells (Bregs)
      and CD4(+)Foxp3(+) regulatory T cell (Tregs) in immune tolerance of cow milk
      allergy of late eczematous reactions.
AB  - Foxp3-expressing cells among CD19(+)CD5(+) B cells were identified as regulatory
      B cells. Food allergy manifesting as late eczematous reactions is regarded as a
      non-IgE-mediated food allergy. The diagnosis for milk allergy manifesting as late
      eczematous reactions was made on the basis of the findings obtained from a double
      blind placebo-controlled food challenge in patients with atopic dermatitis.
      Twelve patients with milk allergy and 12 patients who could tolerate milk were
      selected. On casein stimulation, the CD19(+)CD5(+)Foxp3(+) B cell (Breg) fraction
      in CD5(+) B cells decreased from 4.4+/-1.1% to 3.1+/-0.7% (P=0.047, n=12) in the
      milk allergy group and increased from 4.4+/-1.3% to 5.2+/-1.4% (P=0.001, n=10) in
      the milk-tolerant group. On the other hand, on allergen stimulation, the number
      of CD4(+)Foxp3(+) regulatory T cells (Tregs) in the milk allergy group and milk
      tolerant group increased from 2.6+/-0.7% to 3.4+/-0.6% (P=0.014, n=9) and from
      2.7+/-1.0% to 3.5+/-1.0% (P=0.038, n=10), respectively. In conclusion, allergen
      specific responses of Bregs, rather than those of Tregs, seem to influence the
      immune responses (i.e., allergy or tolerance) to a food allergen.

PMID- 22398310
TI  - Simulations of a micro-PET system based on liquid xenon.
AB  - The imaging performance of a high-resolution preclinical micro-positron emission
      tomography (micro-PET) system employing liquid xenon (LXe) as the gamma-ray
      detection medium was simulated. The arrangement comprises a ring of detectors
      consisting of trapezoidal LXe time projection ionization chambers and two arrays
      of large area avalanche photodiodes for the measurement of ionization charge and
      scintillation light. A key feature of the LXePET system is the ability to
      identify individual photon interactions with high energy resolution and high
      spatial resolution in three dimensions and determine the correct interaction
      sequence using Compton reconstruction algorithms. The simulated LXePET imaging
      performance was evaluated by computing the noise equivalent count rate, the
      sensitivity and point spread function for a point source according to the NEMA
      NU4 standard. The image quality was studied with a micro-Derenzo phantom. Results
      of these simulation studies included noise equivalent count rate peaking at 1326
      kcps at 188 MBq (705 kcps at 184 MBq) for an energy window of 450-600 keV and a
      coincidence window of 1 ns for mouse (rat) phantoms. The absolute sensitivity at
      the center of the field of view was 12.6%. Radial, tangential and axial
      resolutions of (22)Na point sources reconstructed with a list-mode maximum
      likelihood expectation maximization algorithm were <=0.8 mm (full-width at half
      maximum) throughout the field of view. Hot-rod inserts of <0.8 mm diameter were
      resolvable in the transaxial image of a micro-Derenzo phantom. The simulations
      show that a LXe system would provide new capabilities for significantly enhancing
      PET images.

PMID- 22398311
TI  - Comparison between external beam radiotherapy (70 Gy/74 Gy) and permanent
      interstitial brachytherapy in 890 intermediate risk prostate cancer patients.
AB  - PURPOSE: Aim of this analysis was to compare biochemical no evidence of disease
      (bNED) rates in intermediate-risk prostate-cancer patients treated at two centres
      of excellence using different approaches: permanent interstitial brachytherapy
      (BT) and external beam radiotherapy (EBRT). MATERIALS AND METHODS: A total of 890
      intermediate-risk prostate-cancer patients, who were treated from 1998 to 2008,
      were identified in the two local databases. In Utrecht 601 patients received I
      125 BT applying a dose of 144 Gy. In Vienna 289 patients were treated by EBRT,
      applying a local dose of 70 Gy in 105 patients and 74 Gy in 184 patients. bNED
      rates (Phoenix-definition) were assessed. RESULTS: Median follow-up was 48 months
      (1-150). 5-Year actuarial bNED-rates were 81% for BT-patients and 75% for EBRT
      patients (67% for 70 Gy and 82% for 74 Gy), respectively. In univariate analysis
      no difference between BT and EBRT could be detected. In multivariate analysis
      including tumour-stage, GleasonScore, initial PSA, hormonal therapy and treatment
      centre (BT vs. EBRT) only T-stage, GleasonScore and PSA were found to be
      significant. Additional analysis including radiation dose showed the same
      outcome. CONCLUSIONS: Intermediate-risk prostate cancer patients treated by
      permanent interstitial brachytherapy show biochemical tumour-control-rates which
      are comparable to EBRT of 74 Gy.

PMID- 22398309
TI  - Homeostatic signals do not drive post-thymic T cell maturation.
AB  - Recent thymic emigrants, the youngest T cells in the lymphoid periphery, undergo
      a 3 week-long period of functional and phenotypic maturation before being
      incorporated into the pool of mature, naive T cells. Previous studies indicate
      that this maturation requires T cell exit from the thymus and access to secondary
      lymphoid organs, but is MHC-independent. We now show that post-thymic T cell
      maturation is independent of homeostatic and costimulatory pathways, requiring
      neither signals delivered by IL-7 nor CD80/86. Furthermore, while CCR7/CCL19,21
      regulated homing of recent thymic emigrants to the T cell zones within the
      secondary lymphoid organs is not required for post-thymic T cell maturation, an
      intact dendritic cell compartment modulates this process. It is thus clear that,
      unlike T cell development and homeostasis, post-thymic maturation is focused not
      on interrogating the T cell receptor or the cell's responsiveness to homeostatic
      or costimulatory signals, but on some as yet unrecognized property.

PMID- 22398312
TI  - Involved field radiation therapy following high dose chemotherapy and autologous
      stem cell transplant benefits local control and survival in refractory or
      recurrent Hodgkin lymphoma.
AB  - BACKGROUND AND PURPOSE: Patients with recurrent or primary refractory Hodgkin
      lymphoma (HL) treated with high dose chemotherapy (HDT) and autologous stem cell
      transplant (ASCT) commonly relapse post-ASCT in previous disease sites. We sought
      to evaluate involved field radiation therapy (IFRT) following ASCT and patterns
      of recurrence, overall survival (OS), and disease specific survival (DSS).
      METHODS AND MATERIALS: Between May 1993 and October 2003, 62 (n=66) evaluable
      patients with refractory/relapsed HL underwent HDT followed by ASCT. Thirty-two
      (52%) patients received IFRT following transplant. Survival was calculated from
      the day of hematopoietic stem cell infusion. RESULTS: Median follow-up was 2.3
      years (range 0.03-11.56). Estimated 3-year OS (p=0.05) and DSS (p=0.08) were
      69.6% and 82.1% with IFRT and 40% and 57.6% without IFRT on univariate analysis.
      B-symptoms were adverse on univariate (p=0.007) and multivariate (p=0.01)
      analysis. HL patients who received IFRT following ASCT had improved local control
      in areas of previously recurrent disease (p=0.03). CONCLUSION: OS and DSS showed
      marginal benefit at 3 years. Given the retrospective nature of our study and
      attendant selection bias that can be both positive and negative, a future
      prospective study is warranted to better understand the value of IFRT in the
      transplant setting.

PMID- 22398313
TI  - Prevalence and peak incidence of acute and late normal tissue morbidity in the
      DAHANCA 6&7 randomised trial with accelerated radiotherapy for head and neck
      cancer.
AB  - BACKGROUND AND PURPOSE: The aim of this report was to describe the incidence and
      prevalence of acute and late morbidity in the DAHANCA 6&7 multicentre randomised
      trial with accelerated radiotherapy for squamous cell carcinoma of the head and
      neck. MATERIALS AND METHODS: The DAHANCA 6&7 study included 1476 patients
      eligible for primary radiotherapy alone. Patients were randomised between five or
      six weekly fractions of conventional radiotherapy. The prescribed dose was 66-68
      Gy in 33-34 fractions. All patients were seen weekly during treatment and at
      regular intervals after completion where detailed morbidity recording was done.
      Reports from 1468 patients were available for analysis of treatment related
      morbidity. RESULTS: Accelerated radiotherapy caused a significant (p<0.05)
      increase in the peak incidence of: use of analgesics (53% vs. 65%), dysphagia
      (35% vs. 45%), mucosal oedema (52% vs. 59%), and mucositis (33% vs. 53%). All
      acute reactions were reversible and healed within three months after
      radiotherapy. Loss of taste, xerostomia, and acute skin reaction was not
      different between the two groups. For all late endpoints except fibrosis and
      atrophy a decline in prevalence was observed in the years after radiotherapy,
      there was no significant difference between randomisation arms in any of the late
      endpoints. CONCLUSIONS: Six fractions per week, resulting in a one-week reduction
      in overall treatment time relative to conventional radiotherapy increased acute
      but not late morbidity. Since acceleration improves loco-regional tumour control,
      the schedule represents a significant improvement of the therapeutic ratio for
      head and neck radiotherapy and might be close to the maximal gain possible with
      accelerated fractionation alone.

PMID- 22398314
TI  - Salvage stereotactic reirradiation using the CyberKnife for the local recurrence
      of nasal or paranasal carcinoma.
AB  - PURPOSE: To evaluate the clinical outcome of stereotactic reirradiation using the
      CyberKnife system for recurrent nasal or paranasal carcinoma. MATERIALS AND
      METHODS: From May 2005 to February 2010, 51 patients with local recurrence of
      nasal or paranasal carcinoma were reirradiated using CyberKnife. Tumor volume
      ranged from 3.1 to 204.9 ml (median, 33.8). The previous conventional
      radiotherapy dose ranged from 40 to 70 Gy (median, 60). The median follow-up
      period for surviving patients was 21 months (range, 12-52). The marginal doses
      were 20-41.5 Gy in 1-5 fractions (35 Gy). Toxicities were evaluated with the
      Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The median
      overall survival and local control periods after reirradiation were 14.5 and 9.5
      months, respectively. The 1-year survival and local control rates were 67% and
      62%, respectively. Grade 3 or higher adverse events were observed in 23%. Grade 4
      dermatitis and soft tissue necrosis were observed in 2 and 1 patients who had
      received trimodality combination therapy as their previous treatment,
      respectively. CONCLUSIONS: Salvage stereotactic reirradiation using CyberKnife is
      feasible and effective for the local recurrence of nasal and paranasal
      carcinomas. To further improve treatment outcomes, exploration of better planning
      and dose fractionation, as well as combination chemotherapy would be worthwhile.

PMID- 22398315
TI  - Prevalence and phylogenetic analysis of the current porcine circovirus 2
      genotypes after implementation of widespread vaccination programmes in the USA.
AB  - To determine the prevalence of porcine circovirus 2 (PCV2) genotypes in the USA
      during 2010-2011, 5 years after widespread PCV2 vaccination, serum samples from
      clinically normal pigs that were PCV2 vaccinated (n = 1177), non-vaccinated (n =
      378) or of unknown vaccination status (n = 120), and 100 lung samples from pigs
      diagnosed with PCV-associated disease (PCVAD) were tested. The presence of PCV2,
      PCV1, PCV1-2a and porcine parvovirus (PPV) DNA was determined by PCR.
      Determination of the PCV2 genotype was done by differential PCR and sequencing.
      The prevalence of PCV2a and PCV2b in serum samples was 7.7 % (129/1675) and 8.4 %
      (141/1675), respectively. PCV2a DNA was only detected in non-vaccinated pigs. For
      the 100 PCVAD pigs, the prevalence of PCV2a and PCV2b in lung tissues was 13.0
      and 65.0 %, respectively. Partial PCV2 ORF2 sequences (9-563 nt) were obtained
      from 85 PCV2 DNA-positive samples (24 normal pigs and 61 PCVAD cases).
      Phylogenetic analysis revealed that 12.9 % (11/85) of the sequences belonged to
      the 2E clade and the PCV2a genotype and 87.1 % (74/85) belonged to the 1B clade
      and the PCV2b genotype. The alignment of putative PCV2 capsid amino acid
      sequences revealed possible recombination or mutation between PCV2a and PCV2b
      genotypes. Chimeric PCV1-2a was not detected in any of the samples and the
      prevalence rates of PCV1 and PPV were low. Our results suggest PCV2b is more
      prevalent than PCV2a in PCVAD cases and in vaccinated herds PCV2b circulation is
      common. The data generated in this study provide novel information on the
      distribution of PCV2 genotypes in vaccinated pig populations.

PMID- 22398316
TI  - West Nile virus-induced disruption of the blood-brain barrier in mice is
      characterized by the degradation of the junctional complex proteins and increase
      in multiple matrix metalloproteinases.
AB  - West Nile virus (WNV) encephalitis is characterized by neuroinflammation,
      neuronal loss and blood-brain barrier (BBB) disruption. However, the mechanisms
      associated with the BBB disruption are unclear. Complex interactions between the
      tight junction proteins (TJP) and the adherens junction proteins (AJP) of the
      brain microvascular endothelial cells are responsible for maintaining the BBB
      integrity. Herein, we characterized the relationship between the BBB disruption
      and expression kinetics of key TJP, AJP and matrix metalloproteinases (MMPs) in
      the mice brain. A dramatic increase in the BBB permeability and extravasation of
      IgG was observed at later time points of the central nervous system (CNS)
      infection and did not precede virus-CNS entry. WNV-infected mice exhibited
      significant reduction in the protein levels of the TJP ZO-1, claudin-1, occludin
      and JAM-A, and AJP beta-catenin and vascular endothelial cadherin, which
      correlated with increased levels of MMP-1, -3 and -9 and infiltrated leukocytes
      in the brain. Further, intracranial inoculation of WNV also demonstrated
      increased extravasation of IgG in the brain, suggesting the role of virus
      replication in the CNS in BBB disruption. These data suggest that altered
      expression of junction proteins is a pathological event associated with WNV
      infection and may explain the molecular basis of BBB disruption. We propose that
      WNV initially enters CNS without altering the BBB integrity and later virus
      replication in the brain initiates BBB disruption, allowing enhanced infiltration
      of immune cells and contribute to virus neuroinvasion via the 'Trojan-horse'
      route. These data further implicate roles of multiple MMPs in the BBB disruption
      and strategies to interrupt this process may influence the WNV disease outcome.

PMID- 22398317
TI  - Recombinant nucleocapsid-like particles from dengue-2 induce functional serotype
      specific cell-mediated immunity in mice.
AB  - The interplay of different inflammatory cytokines induced during dengue virus
      infection plays a role in either protection or increased disease severity. In
      this sense, vaccine strategies incorporating whole virus are able to elicit both
      functional and pathological responses. Therefore, an ideal tetravalent vaccine
      candidate against dengue should be focused on serotype-specific sequences. In the
      present work, a new formulation of nucleocapsid-like particles (NLPs) obtained
      from the recombinant dengue-2 capsid protein was evaluated in mice to determine
      the level of protection against homologous and heterologous viral challenge and
      to measure the cytotoxicity and cytokine-secretion profiles induced upon
      heterologous viral stimulation. As a result, a significant protection rate was
      achieved after challenge with lethal dengue-2 virus, which was dependent on
      CD4(+) and CD8(+) cells. In turn, no protection was observed after heterologous
      challenge. In accordance, in vitro-stimulated spleen cells from mice immunized
      with NLPs from the four dengue serotypes showed a serotype-specific response of
      gamma interferon- and tumour necrosis factor alpha-secreting cells. A similar
      pattern was detected when spleen cells from dengue-immunized animals were
      stimulated with the capsid protein. Taking these data together, we can assert
      that NLPs constitute an attractive vaccine candidate against dengue. They induce
      a functional immune response mediated by CD4(+) and CD8(+) cells in mice, which
      is protective against viral challenge. In turn, they are potentially safe due to
      two important facts: induction of serotype specific cell-mediated immunity and
      lack of induction of antiviral antibodies. Further studies in non-human primates
      or humanized mice should be carried out to elucidate the usefulness of the NLPs
      as a potential vaccine candidate against dengue disease.

PMID- 22398319
TI  - Successful percutaneous drainage with iodine irrigation for pancreatic fistulas
      and abscesses after necrotizing pancreatitis.
AB  - OBJECTIVE: To report an uncommon method of managing pancreatic fistulas and
      retroperitoneal abscess. CLINICAL PRESENTATION AND INTERVENTION: A 50-year-old
      man was admitted with fever, abdominal pain, periumbilical fistula and pus in
      stool. Five months before admission, he underwent urgent necrosectomy (7 days
      after onset of pain) and subsequently two more surgeries for necrotizing
      pancreatitis. Ultrasound revealed fluid collection in the retropancreatic space.
      After evacuation of pus, contrast medium instilled through a catheter showed a
      retroperitoneal abscess cavity, retroperitoneal-periumbilical and retroperitoneal
      sigmoidal fistulas. After percutaneous drainage and iodine irrigation, the
      abscess collection and fistulas disappeared. CONCLUSION: In this case,
      percutaneous drainage was a successful option in the management of pancreatic
      fistulas and a retroperitoneal abscess.

PMID- 22398318
TI  - Vaxfectin-adjuvanted plasmid DNA vaccine improves protection and immunogenicity
      in a murine model of genital herpes infection.
AB  - The herpes simplex type 2 (HSV-2) envelope glycoprotein (gD2) was evaluated as a
      potential antigen candidate for a plasmid DNA (pDNA)-based HSV-2 vaccine. The
      pDNA was formulated with Vaxfectin, a cationic lipid-based adjuvant, and tested
      in a murine HSV-2 lethal challenge model. gD2 was expressed as full-length (FL)
      and secreted (S) gD2 forms. A 0.1 ug pDNA dose was tested to distinguish
      treatment conditions for survival and a 100 ug pDNA dose was tested to
      distinguish treatment conditions for reduction in vaginal and latent HSV-2
      copies. Vaxfectin-formulated gD2 pDNA significantly increased serum IgG titres
      and survival for both FL gD2 and S gD2 compared with gD2 pDNA alone. Mice
      immunized with FL gD2 formulated with Vaxfectin showed reduction in vaginal and
      dorsal root ganglia (DRG) HSV-2 copies. The stringency of this protection was
      further evaluated by testing Vaxfectin-formulated FL gD2 pDNA at a high 500
      LD(50) inoculum. At this high viral challenge, the 0.1 ug dose of FL gD2
      Vaxfectin-formulated pDNA yielded 80 % survival compared with no survival for FL
      gD2 pDNA alone. Vaxfectin-formulated FL gD2 pDNA, administered at a 100 ug pDNA
      dose, significantly reduced HSV-2 DNA copy number, compared with FL gD2 DNA
      alone. In addition, 40 % of mice vaccinated with adjuvanted FL pDNA had no
      detectable HSV-2 viral genomes in the DRG, whereas all mice vaccinated with gD2
      pDNA alone were positive for HSV-2 viral genomes. These results show the
      potential contribution of Vaxfectin-gD2 pDNA to a future multivalent HSV-2
      vaccine.

PMID- 22398320
TI  - Oestrogen's regulation of fat metabolism during exercise and gender specific
      effects.
AB  - Early animal, menstrual phase and gender comparative studies inconsistently
      support an oestrogen-induced increase in fat oxidation during exercise. Recent
      advances from studies of cellular signalling and gene expression provide evidence
      for inter-tissue and intramuscular mechanisms that demonstrate oestrogen's
      promotion of skeletal muscle fat oxidative capacity. Oestrogen or oestrogen
      analogues act mainly through oestrogen receptor-alpha in skeletal muscle to
      stimulate the genomic expression of certain other nuclear hormone receptors and
      downstream targets to promote long chain fatty acid (LCFA) uptake, mitochondrial
      shuttling and beta oxidation. Oestrogen increases the availability of LCFA
      substrate by enhancing adipocyte lipolysis and expression of genes promoting
      intramyocellular lipid storage. Oestrogen acts by non-genomic means to increase
      the activation of AMPK that may reinforce some direct genomic actions.

PMID- 22398321
TI  - IL-36 in psoriasis.
AB  - Psoriasis is a common but severe skin disease with significant health
      consequences, both physical and psychological. Evidence has emerged during the
      past several years pointing to a key role for IL-36 in psoriasis. Overexpression
      of IL-36 in mouse skin leads to a disease quite similar to human plaque
      psoriasis, and inhibition of IL-36 in human psoriatic skin ameliorates the
      inflammation. Loss of the natural antagonist of IL-36, IL-36Ra, results in a
      different, more severe skin disease known as pustular psoriasis. These effects
      are likely a consequence of the actions of IL-36 both on cells of the immune
      system as well as on components of skin including fibroblasts and keratinocytes.

PMID- 22398322
TI  - Smoking cessation: present status and future perspectives.
AB  - Smoking is the leading cause of premature mortality in western countries and it
      is important for smokers to stop as early as possible. Several approaches for
      cessation are available but they lack high levels of efficacy. Consequently,
      there is a compelling need for more effective approaches and safer medications to
      aid smokers in achieving long-term abstinence. Expanding knowledge in our
      understanding of the mechanisms involved in tobacco dependence is leading to the
      development of novel therapies and vaccines for smoking cessation, many of which
      are currently in the advanced stage of development and offer promise. Here we
      will review efficacy and safety data from human clinical trials of current and
      emerging therapies and tools which are approved or undergoing investigation.

PMID- 22398323
TI  - Compton scattering spectrum as a source of information of normal and neoplastic
      breast tissues' composition.
AB  - In this work we measured X-ray scatter spectra from normal and neoplastic breast
      tissues using photon energy of 17.44 keV and a scattering angle of 90 degrees ,
      in order to study the shape (FWHM) of the Compton peaks. The obtained results for
      FWHM were discussed in terms of composition and histological characteristics of
      each tissue type. The statistical analysis shows that the distribution of FWHM of
      normal adipose breast tissue clearly differs from all other investigated tissues.
      Comparison between experimental values of FWHM and effective atomic number
      revealed a strong correlation between them, showing that the FWHM values can be
      used to provide information about elemental composition of the tissues.

PMID- 22398324
TI  - Radioluminescence of rare-earth doped aluminum oxide.
AB  - Al(2)O(3):C is one of the most used radioluminescence materials for fiberoptic
      dosimetry due mainly to its high efficiency. However, this compound presents the
      drawback of emitting in the spectral region, where the spurious radioluminescence
      of fibers is also important. In this work, sintered samples of Al(2)O(3):C doped
      with Tb, Sm, Ce and Tm have been prepared by combustion synthesis and their
      radioluminescence responses have been evaluated. The influence of the different
      activators on the radioluminescence spectra has been investigated.

PMID- 22398325
TI  - Analysis and comparison of monoenergetic fast neutron fluence determination using
      238U samples at different positions with respect to the neutron source.
AB  - Using two (238)U samples placed in a gridded ionization chamber and a parallel
      plate fission chamber, fluence of monoenergetic fast neutrons was determined.
      Four runs of measurements were performed. Analysis showed that although the
      neutron fluences for the two (238)U samples differ by 20-33 times in the present
      work, the fluences at the position of the sample in the gridded ionization
      chamber determined by the two ways are in agreement within experimental
      uncertainties.

PMID- 22398326
TI  - Do radioactive half-lives vary with the Earth-to-Sun distance?
AB  - Recently, Jenkins, Fischbach and collaborators have claimed evidence that
      radionuclide half-lives vary systematically over a +/-0.1% range as a function of
      the oscillating distance between the Earth and the Sun, based on multi-year
      activity measurements. We have avoided the time-dependent instabilities to which
      such measurements are susceptible by directly measuring the half-life of (198)Au
      (t(1/2)=2.695 d) on seven occasions spread out in time to cover the complete
      range of Earth-Sun distances. We observe no systematic oscillations in half-life
      and can set an upper limit on their amplitude of +/-0.02%.

PMID- 22398328
TI  - Energy dissipation distributions and dissipative atomic processes in amplitude
      modulation atomic force microscopy.
AB  - Instantaneous and average energy dissipation distributions in the nanoscale due
      to short and long range interactions are described. We employ both a purely
      continuous and a semi-discrete approach to analyze the consequences of this
      distribution in terms of rate of heat generation, thermal flux, adhesion
      hysteresis, viscoelasticity and atomic dissipative processes. The effects of peak
      values are also discussed in terms of the validity of the use of average values
      of power and energy dissipation. Analytic expressions for the instantaneous power
      are also derived. We further provide a general expression to calculate the
      effective area of interaction for fundamental dissipative processes and relate it
      to the energy distribution profile in the interaction area. Finally, a semi
      discrete approach to model and interpret atomic dissipative processes is proposed
      and shown to lead to realistic values for the atomic bond dissipation and
      viscoelastic atomic processes.

PMID- 22398327
TI  - The indication of tracheotomy conditions the predictors of time to decannulation
      in critical patients.
AB  - OBJECTIVE: Variables predicting optimal timing for tracheostomy decannulation
      remain unknown. We aimed to determine whether classifying patients into two
      groups according to their indications for tracheostomy could identify variables
      associated with time to decannulation. DESIGN: A prospective, observational
      cohort study was carried out. LOCATION: Two medical-surgical ICUs. PATIENTS: We
      included all patients tracheostomized during ICU stay, excluding patients with do
      not-resuscitate orders, tracheostomies for long-term airway control,
      neuromuscular disease, or neurological damage. Patients were classified into two
      groups: patients tracheostomized due to prolonged weaning and/or prolonged
      mechanical ventilation (Group 1), and patients tracheostomized due to low level
      of consciousness or inability to manage secretions (Group 2). INTERVENTIONS:
      Patients were weaned and decannulated according to established protocols. MAIN
      VARIABLES: We recorded the following variables: time to tracheostomy, forced
      vital capacity, peak flow, suctioning requirements, Glasgow Coma Score (GCS),
      characteristics of respiratory secretions, and swallowing function. Statistical
      analyses included Cox-proportional multivariate analysis with time to
      decannulation as the dependent variable. RESULTS: A total of 227 patients were
      tracheostomized in the ICUs; of these, 151 were finally included in the study. In
      the multivariate analysis, time to decannulation in Group 1 was associated with
      the male gender (HR 1.74 (1.04-2.89), p= 0.03), age>60 years (HR 0.58 (0.36
      0.91), p= 0.02), high suctioning frequency (HR 0.81 (0.67-0.97), p= 0.02), low
      forced vital capacity (HR 0.48 (0.28-0.82), p<0.01), and low peak flow (HR 0.25
      (0.14-0.46), p<0.01). In Group 2 time to decannulation was associated to GCS >13
      (HR 2.73 (1.51-4.91), p<0.01), high suctioning frequency (HR 0.7 (0.54-0.91),
      p<0.01), and inadequate swallowing (HR 1.97 (1.11-3.52), p=0.02). CONCLUSION:
      Variables associated with longer time to decannulation in ICU-tracheostomized
      patients differ with the indications for tracheostomy.

PMID- 22398329
TI  - Impact of early chest radiography and empirical antibiotherapy on delay in the
      diagnosis of pulmonary tuberculosis.
AB  - OBJECTIVE: The treatment of community-acquired pneumonia relies on empirical
      antibacterial treatment, guided by chest X-ray. We evaluated the impact of this
      practice on delay in the diagnosis of pulmonary tuberculosis. PATIENTS AND
      METHODS: We performed a retrospective monocentric study on 64 documented cases of
      pulmonary tuberculosis. RESULTS: Empirical antibacterial treatment was prescribed
      between the first symptoms and pulmonary tuberculosis diagnosis in 42.2% of
      cases. The median delay between first contact with a healthcare provider and
      pulmonary tuberculosis treatment initiation (medical delay) was 13.5 days. The
      factors associated with medical delay above 30 days were alcohol abuse (OR 7.62;
      P = 0.02), and late chest X-ray (OR 9.33; P = 0.01). Empirical antibacterial
      treatment was more frequent in case of late chest X-ray (P = 0.02) and increased
      the risk of medical delay above 7 days (OR 6.3; P = 0.05). CONCLUSION: When lower
      respiratory tract infection is suspected, early chest X-ray reduces the empirical
      use of antibacterial agents and decreases delay in the diagnosis of pulmonary
      tuberculosis.

PMID- 22398330
TI  - Pulmonary hemorrhage after the use of sildenafil.

PMID- 22398331
TI  - Aorto-porto-caval micro-rheological differences of red blood cells in laboratory
      rats: further deformability and ektacytometrial osmoscan data.
AB  - Investigation of regional hemorheological properties are important in ischemia
      reperfusion experimental surgical and microsurgical research models, however, the
      physiological arterio-venous as well as porto-caval differences in erythrocyte
      deformability and aggregation are still controversial. In this study, besides
      measuring blood pH, blood gases, lactate concentration and hematological
      parameters we determined erythrocyte deformability (rotational ektacytometer)
      together with osmoscan data as well as erythrocyte aggregation (light
      transmittance aggregometer) in blood samples taken from the portal vein, caudal
      caval vein and abdominal aorta of rats. Blood pH, partial blood gas pressures
      showed the anticipated physiological differences. Leukocyte count was lower in
      arterial blood; hematocrit, erythrocyte and platelet count was higher in systemic
      and portal venous blood. The lowest elongation index values were measured in
      arterial blood, the highest in venous and portal venous blood showed values in
      between. The osmoscan data did not show important differences. Erythrocyte
      aggregation M index 5 s showed the lowest values in arterial, higher in systemic
      venous and portal venous blood samples. M index 10 s showed significantly low
      values in systemic venous blood. M1 values were slightly higher in arterial blood
      compared to venous blood but the highest were in portal venous blood. Erythrocyte
      deformability and aggregation may show aorto-porto-caval differences in the rat.
      The appropriate control examinations thus are important in experimental surgical
      and microsurgical research models.

PMID- 22398332
TI  - Comparative performance evaluation of a flat detector and an image intensifier
      angiographic system both used for interventional cardiology procedures in adult
      and pediatric patients.
AB  - PURPOSE: To compare two angiography systems of different image capture
      technology, one with flat detector (FD) and one with image intensifier (II), in
      terms of entrance surface air kerma (ESAK) rate, detector dose (DD) rate and
      image quality (IQ), in interventional cardiology procedures concerning both adult
      and pediatric patients. MATERIALS AND METHODS: In order to determine ESAK and DD
      rates, a digital dosimeter and polymethylmethacrylate (PMMA) plates were used.
      For the evaluation of IQ, two contrast objects (the Leeds TOR 18FG and a 5 mm
      thick Aluminum plate) were used and two figures of merit were defined in
      fluoroscopy and cine acquisition modes. Measurements of ESAK, DD rates and IQ
      were made for various fields of view, pulse and frame acquisition rates. RESULTS:
      For the particular setup used in this study was noted that ESAK values in the II
      system were generally larger than the respective values in the FD system (on
      average 70% for fluoro mode, 5 times for cine mode). When halving the fluoroscopy
      pulse rate, reduction in ESAK was not proportional, in fluoroscopy mode. Image
      quality evaluations indicated that II performs better in terms of low contrast
      sensitivity (LCS) and signal-to-noise ratio (SNR) than the FD system which
      performs better regarding high contrast resolution (HCR). However, when
      considering image quality in relation to ESAK the FD system performs better than
      the II system (with the exception of low thicknesses and zooms for high pulse
      rates in the fluoroscopy mode). CONCLUSIONS: The FD system, generally, provides a
      better image quality-dose relation than the II system although II unit provides
      better LCS and SNR. This means that with the right adjustments to both systems,
      FD unit is able to provide same image quality with lower dose. However, newer
      technology does not automatically imply better image quality and further
      investigation is necessary for deriving safe conclusions for units which utilize
      different capture technology.

PMID- 22398333
TI  - Evaluating validity and test-retest reliability in four drive for muscularity
      questionnaires.
AB  - The current study assessed relationships among four commonly used drive for
      muscularity questionnaires, along with their 7 and 14 day test-retest
      reliability. Sample 1 was comprised of young British adult males (N=272;
      M(AGE)=20.3) who completed the questionnaires once. Sample 2, a group of young
      British adult males (N=54, M(AGE)=19.3), completed the questionnaires three times
      spaced 7 and 14 days apart. Correlations among Sample 1 ranged from .20 to .82
      providing evidence for concurrent and discriminant validities. Evidence for test
      retest reliability emerged with intraclass correlations ranging from .78 to .95
      (p<.001) and generally nonsignificant t-tests (p>.05). Overall, the data support
      the psychometric properties of the drive for muscularity inventories; however,
      the shared variance (35-67%) hints that refinement is possible.

PMID- 22398335
TI  - Blindness, weakness, and tingling.
AB  - A previously healthy 50-year-old man complained of acute bilateral loss of vision
      over 24 hours associated with tingling of his hands and feet. During the first 48
      hours of hospitalization, he evolved quadriplegia, facial diplegia, bulbar palsy,
      and respiratory distress requiring ventilator assistance. At the same time vision
      deteriorated to hand motions. Lumbar puncture, electromyography, and clinical
      findings were all consistent with Guillain-Barre syndrome. The diagnosis of
      concomitant bilateral optic neuritis was made. Tests for immunological,
      inflammatory, infectious, or genetic diseases were unremarkable. Within weeks,
      repeated treatments with intravenous immunoglobulin, plasmapheresis, and high
      dose parenteral corticosteroids led to resolution of motor findings, although
      visual acuity improved only to 20/100 OD and count fingers at 6 feet OS. Guillain
      Barre syndrome-associated optic neuritis is rare and may be associated with an
      underlying Mycoplasma pneumoniae infection.

PMID- 22398334
TI  - Anisakis simplex recombinant allergens increase diagnosis specificity preserving
      high sensitivity.
AB  - BACKGROUND: So far, the frequency of Anisakis simplex-specific IgE antibodies has
      been determined by skin prick tests (SPTs) and the ImmunoCAP system. These
      commercial methods have good sensitivity, but their specificity is poor because
      they use complete parasite extracts. Our aim was to determine the frequency of
      sensitization to A. simplex using recombinant Ani s 1, Ani s 3, Ani s 5, Ani s 9
      and Ani s 10 and to evaluate these allergens for diagnosis, comparing their
      performance with the commercial methods. PATIENTS AND METHODS: We conducted a
      descriptive, cross-sectional validation study performed in an allergy outpatient
      hospital clinic. Patients without fish-related allergy (tolerant patients, n =
      99), and A. simplex-allergic patients (n = 35) were studied by SPTs, ImmunoCAP
      assays and detection of specific IgE to A. simplex recombinant allergens by dot
      blotting. RESULTS: SPTs and ImmunoCAP assays were positive in 18 and 17% of
      tolerant patients, respectively. All A. simplex-allergic patients had positive
      SPTs and ImmunoCAP assays. Specific IgE against at least one of the A. simplex
      recombinant allergens tested was detected in 15% of sera from tolerant patients
      and in 100% of sera from A. simplex-allergic patients. Detection of at least one
      A. simplex recombinant allergen by dot blotting and ImmunoCAP assay using
      complete extract showed a diagnostic sensitivity of 100% with both methods.
      However, the specificity of dot blotting with A. simplex recombinant allergens
      was higher compared with ImmunoCAP (84.85 vs. 82.83%). CONCLUSIONS: There are 15%
      of tolerant patients with specific IgE against important A. simplex allergens.
      The recombinant allergens studied here increase the specificity of A. simplex
      diagnosis while keeping the highest sensitivity. A. simplex recombinant allergens
      should be included with A. simplex allergy diagnostic tests to improve their
      specificity.

PMID- 22398338
TI  - Yoga and change: the power of partnership.

PMID- 22398336
TI  - School-based approaches to the correction of refractive error in children.
AB  - The World Health Organization estimates that 13 million children aged 5-15 years
      worldwide are visually impaired from uncorrected refractive error. School vision
      screening programs can identify and treat or refer children with refractive
      error. We concentrate on the findings of various screening studies and attempt to
      identify key factors in the success and sustainability of such programs in the
      developing world. We reviewed original and review articles describing children's
      vision and refractive error screening programs published in English and listed in
      PubMed, Medline OVID, Google Scholar, and Oxford University Electronic Resources
      databases. Data were abstracted on study objective, design, setting,
      participants, and outcomes, including accuracy of screening, quality of
      refractive services, barriers to uptake, impact on quality of life, and cost
      effectiveness of programs. Inadequately corrected refractive error is an
      important global cause of visual impairment in childhood. School-based vision
      screening carried out by teachers and other ancillary personnel may be an
      effective means of detecting affected children and improving their visual
      function with spectacles. The need for services and potential impact of school
      based programs varies widely between areas, depending on prevalence of refractive
      error and competing conditions and rates of school attendance. Barriers to
      acceptance of services include the cost and quality of available refractive care
      and mistaken beliefs that glasses will harm children's eyes. Further research is
      needed in areas such as the cost-effectiveness of different screening approaches
      and impact of education to promote acceptance of spectacle-wear. School vision
      programs should be integrated into comprehensive efforts to promote healthy
      children and their families.

PMID- 22398339
TI  - Training issues in yoga therapy and mental health treatment.

PMID- 22398340
TI  - Thoughts on legal and ethical concepts on the professional development of
      Ayurveda in the U.S.
AB  - The following is a transcript of a talk given by Wynn Werner, who is a board
      member of the National Ayurvedic Medical Association (NAMA) and member of the
      NAMA standards committee, at the NAMA conference in April 2010. In this talk,
      Werner discusses the legal and licensing challenges facing Ayurvedic
      practitioners in the United States. IAYT finds the work of NAMA on the issue of
      professional development to be both educational and thought-provoking for our own
      field's parallel process. We present this transcript to contribute to the
      conversation within the yoga therapy community.

PMID- 22398341
TI  - Don't put yoga in a small box: the challenges of scientifically studying yoga.

PMID- 22398342
TI  - Transforming trauma: a qualitative feasibility study of integrative restoration
      (iRest) yoga Nidra on combat-related post-traumatic stress disorder.
AB  - This eight-week study examined the feasibility of offering weekly classes in
      Integrative Restoration (iRest), a form of mindfulness meditation, to military
      combat veterans at a community mental health agency in the San Francisco Bay
      Area. Participants were 16 male combat veterans (15 Vietnam War and 1 Iraq War)
      of mixed ethnicity, aged 41 to 66 years, suffering from posttraumatic stress
      disorder (PTSD). The 11 participants who completed the study reported reduced
      rage, anxiety, and emotional reactivity, and increased feelings of relaxation,
      peace, self-awareness, and self-efficacy, despite challenges with mental focus,
      intrusive memories, and other concerns. All participants reported they would have
      attended ongoing iRest classes at the agency approximately once per week.

PMID- 22398343
TI  - Yoga for women living with breast cancer-related arm morbidity: findings from an
      exploratory study.
AB  - Treatments for breast cancer assault the body and can disrupt the relationship
      between body, mind, and spirit. In this article, we discuss the ways in which
      yoga was experienced and understood as a healing therapy among ten female breast
      cancer survivors between the ages of 26 and 70 and living with treatment-related
      arm morbidity. The women participated in 6 weekly sessions of gentle Iyengar yoga
      and responded to open-ended surveys before and after the intervention. The
      majority of women reported physical, emotional, and spiritual benefits from the
      practice of yoga. Specific benefits included improvements in physical function
      and relief from symptoms related to treatment; increased peace of mind and hope;
      and connection to other yoga participants. Integral to this healing process was
      social support from other breast cancer survivors.

PMID- 22398344
TI  - Influence of Hatha yoga on physical activity constraints, physical fitness, and
      body image of breast cancer survivors: a pilot study.
AB  - Breast cancer survivors often experience changes in their perception of their
      bodies following surgical treatment. These changes in body image may increase
      self-consciousness and perceptions of physical activity constraints and reduce
      participation in physical activity. While the number of studies examining
      different types of yoga targeting women with breast cancer has increased, studies
      thus far have not studied the influence that Hatha yoga has on body image and
      physical activity constraints. The objective of this study was to explore the
      changes that occur in breast cancer survivors in terms of body image, perceived
      constraints, and physical fitness following an 8-week Hatha yoga intervention.
      This study used a nonrandomized two-group pilot study, comparing an 8-week Hatha
      yoga intervention with a light exercise group, both designed for women who were
      at least nine months post-treatment for breast cancer. Both quantitative and
      qualitative data were collected in the areas of body image, physical activity
      constraints, and physical fitness. Findings indicated that quantitatively, yoga
      participants experienced reductions in physical activity constraints and
      improvements in lower- and upper-body strength and flexibility, while control
      participants experienced improvements in abdominal strength and lower-body
      strength. Qualitative findings support changes in body image, physical activity
      constraints, and physical fitness for the participants in the yoga group. In
      conclusion, Hatha yoga may reduce constraints to physical activity and improve
      fitness in breast cancer survivors. More research is needed to explore the
      relationship between Hatha yoga and improvements in body image.

PMID- 22398345
TI  - The impact of a short-term iyengar yoga program on the health and well-being of
      physically inactive older adults.
AB  - BACKGROUND: With the current challenge of rapidly aging populations, practices
      such as yoga may help older adults stay physically active, healthy, and
      fulfilled. METHODS: The impact of an 8-week Iyengar yoga program on the holistic
      health and well-being of physically inactive people aged 55 years and over was
      assessed. Thirty-eight older adults (mean age 73.21+/-8.38 years; 19
      intervention, 19 control) engaged in either twice-weekly yoga classes or
      continued their usual daily routines. Physical health measures were muscle
      strength, active range of motion, respiratory function (FEV1), resting blood
      pressure, and immune function (salivary IgA and lysozyme). Self-perceived
      general, physical, mental, spiritual, and social health and well-being were
      assessed with the Life's Odyssey Questionnaire and the SF12v2TM Health Survey.
      RESULTS: Muscle strength, active range of motion, physical well-being, and
      aspects of mental well-being (emotional well-being and self-care) improved
      significantly in the yoga group (p<.05). Median changes in most of these
      variables were also significantly different from those in the control group.
      CONCLUSIONS: Participation in Iyengar yoga programs by older people is beneficial
      for health and well-being, and greater availability of such programs could
      improve quality of life.

PMID- 22398346
TI  - Immediate effect of sukha pranayama on cardiovascular variables in patients of
      hypertension.
AB  - Hypertension is one of the most common health disorders, and yoga has been shown
      to be an effective adjunct therapy in its management. Earlier studies have
      reported blood pressure (BP)-lowering effects of slow, deep breathing after 3
      weeks and 3 months of training and beneficial immediate effects of slow, deep
      breathing in reducing premature ventricular complexes and lowering blood
      pressure. None of these immediate studies used the concept of pranayama,
      involving conscious internal awareness of the whole breathing process. This study
      was undertaken to determine the immediate cardiovascular effects of sukha
      pranayama in hypertensive patients. METHODS: Twenty-three hypertensive patients
      attending the Yoga OPD at JIPMER were recruited for the study and instructed to
      perform sukha pranayama for 5 minutes at the rate of 6 breaths/min. This
      pranayama involves conscious, slow and deep breathing with equal duration for
      inhalation and exhalation. Heart rate (HR) and BP were recorded before and
      immediately after the intervention. RESULTS: Post-intervention statistical
      analysis revealed a significant (p < .05) reduction in HR and a highly
      significant (p < .001) reduction in systolic pressure, pulse pressure, mean
      arterial pressure, rate-pressure product, and double product with an
      insignificant fall in diastolic pressure. DISCUSSION: It is concluded that sukha
      pranayama at the rate of 6 breaths/minute can reduce HR and BP in hypertensive
      patients within 5 minutes of practice. This may be due to a normalization of
      autonomic cardiovascular rhythms as a result of increased vagal modulation and/or
      decreased sympathetic activity and improved baroreflex sensitivity. Further
      studies are required to understand possible mechanisms underlying this beneficial
      immediate effect and to determine how long such a beneficial effect persists.

PMID- 22398347
TI  - Yoga for heart failure patients: a feasibility pilot study with a multiethnic
      population.
AB  - BACKGROUND: Congestive heart failure (CHF) is highly prevalent and the most
      costly cardiovascular illness in the United States. Yoga is known to be effective
      in lowering stress, lessening depression, and increasing physical fitness and may
      be used as an adjuvant management program for CHF patients. PRIMARY STUDY
      OBJECTIVE: To determine the feasibility of a yoga intervention program among a
      multiethnic CHF population living in underserved neighborhoods. METHODS:
      Uncontrolled intervention trial. SETTING: Kaiser Permanente Medical Centers,
      Richmond and Oakland, California. PARTICIPANTS: 14 CHF patients (7 female), mean
      age 64 (SD=6.4) years, and 62% African-American. INTERVENTION: Eight-week,
      2x/week, 1-hr yoga classes that included meditation, breathing exercises, gentle
      yoga poses, and relaxation. PRIMARY OUTCOME MEASURES: The intervention
      feasibility was measured by recruitment rates, participant retention and
      adherence. Body weight and self-reported depression and quality of life were
      measured before and after the intervention. RESULTS: Among the 14 patients
      enrolled, 13 completed the intervention. Of those who completed the trial, 92%
      attended at least 50% of the classes. There was a significant reduction in weight
      (-3.5 lb, p=0.01) and improvement in the severity of depression (p<0.05), as well
      as a trend toward increased quality of life (p=08). No adverse events were
      observed. CONCLUSIONS: This pilot trial demonstrates that it is feasible for
      patients with CHF to incorporate yoga into their lifestyle. Yoga may help with
      routine disease management, prevention of fluid retention, and improvement of
      depression and quality of life. A larger trial is needed to confirm efficacy and
      to determine the long-term effects on other important outcomes, such as hospital
      re-admission rates or prognostic biomarkers.

PMID- 22398348
TI  - Development of the beliefs about yoga scale.
AB  - Beliefs about yoga may influence participation in yoga and outcomes of yoga
      interventions. There is currently no scale appropriate for assessing these
      beliefs in the general U.S. population. This study took the first steps in
      developing and validating a Beliefs About Yoga Scale (BAYS) to assess beliefs
      about yoga that may influence people's engagement in yoga interventions. Items
      were generated based on previously published research about perceptions of yoga
      and reviewed by experts within the psychology and yoga communities. 426 adult
      participants were recruited from an urban medical center to respond to these
      items. The mean age was 40.7 (SD=13.5) years. Participants completed the BAYS and
      seven additional indicators of criterion-related validity. The BAYS demonstrated
      internal consistency (11 items; alpha=0.76) and three factors emerged: expected
      health benefits, expected discomfort, and expected social norms. The factor
      structure was confirmed: x2 (41, n=213)=72.06, p<.001; RMSEA=06, p=.23. Criterion
      related validity was supported by positive associations of the BAYS with past
      experiences and future intentions related to yoga. This initial analysis of the
      BAYS demonstrated that it is an adequately reliable and valid measure of beliefs
      about yoga with a three-factor structure. However, the scale may need to be
      modified based on the population to which it is applied.

PMID- 22398349
TI  - This I know for sure. The student-teacher relationship in yoga therapeutics.

PMID- 22398350
TI  - Yoga therapist, heal thyself: a reflection on ahimsa and service.

PMID- 22398351
TI  - Mass disasters and mind-body solutions: evidence and field insights.
AB  - Treatment for the psychological consequences of mass disasters is essential to
      the recovery of individuals and communities. Little is known about how to provide
      effective mental health interventions when there are thousands of victims and
      little, if any, access to care. Post-disaster research and program evaluations
      suggest that mind-body practices can provide significant relief of anxiety,
      depression, posttraumatic stress, and physical ailments. Mind-body programs are
      inexpensive, adaptable to different cultures and conditions, and can be taught
      rapidly to large numbers of people, including community leaders, to create a
      sustainable resource for local mental health needs. The challenges of doing
      research in disaster areas are illustrated using examples from field studies.
      Potential risks of administering programs to vulnerable populations are
      discussed, with program design recommendations. The development of safe,
      effective, trauma-sensitive, culturally appropriate, sustainable programs
      requires research and collaboration among healthcare professionals, mind-body
      trainers, researchers, academic institutions, government agencies, and non
      governmental humanitarian organizations.

PMID- 22398352
TI  - A protocol and pilot study for managing fibromyalgia with yoga and meditation.
AB  - Fibromyalgia is a chronic syndrome characterized by widespread pain, sleep
      disturbance, stiffness, fatigue, headache, and mood disorders. Recent research
      has resulted in an improved understanding of fibromyalgia and its possible
      causes. This article highlights some of the current research, discusses a
      strategy for using yoga and meditation as a therapy for fibromyalgia sufferers,
      and presents the results of a preliminary 8-week study using yoga and meditation
      to help manage fibromyalgia symptoms. The study of 11 participants found
      significant improvement in the overall health status of the participants and in
      symptoms of stiffness, anxiety, and depression. Significant improvements were
      also seen in the reported number of days "felt good" and number of days "missed
      work" because of fibromyalgia. Nonsignificant improvements were seen in measures
      of pain, fatigue, and how one felt in the morning. Effect sizes were medium to
      large for most tested areas. This study supports the benefits of yoga and
      meditation for individuals with fibromyalgia and encourages further research to
      explore their use as standard therapies for fibromyalgia.

PMID- 22398353
TI  - Partner yoga for establishing boundaries in relationship: a transpersonal somatic
      approach.
AB  - This article is written for yoga therapists and psychotherapists who work with
      couples who have difficulty setting boundaries and maintaining individuality in
      their relationships. Partner yoga, transpersonal psychology, and somatic-based
      psychology are approaches that can provide clients with a holistic system of
      therapy to encourage healthy boundaries and emotional connection. The process of
      partner yoga is described from a transpersonal, somatically oriented approach.
      Examples of specific asanas, or yoga poses, are discussed alongside the special
      considerations that a therapist must consider when exploring boundaries and
      communication through partner yoga. Insights from individual case sessions with
      couples are included to illustrate the process of differentiation and the
      possibility of experiencing a transpersonal union through partner yoga.

PMID- 22398354
TI  - The psychological benefits of yoga practice for older adults: evidence and
      guidelines.
AB  - Yoga is an effective complementary approach to health maintenance and promotion
      for older adults and has been demonstrated to support many dimensions of
      psychological wellbeing, from everyday stress to anxiety, depression, and coping
      with health challenges. Yoga has the potential to be even more effective when
      consciously and systematically integrated into an individual's overall self-care
      and medical care program, through deliberate and open dialogue among patients,
      healthcare professionals, and yoga professionals. The purpose of this article is
      to (1) briefly review the psychological benefits of yoga practice for older
      adults; (2) outline practice guidelines for older adult yoga, including key
      postures; and (3) provide some basic practical guidelines for both healthcare
      professionals referring patients to yoga and yoga teachers interested in working
      with older adults.

PMID- 22398355
TI  - The phenotypic characterization of A13/BACii, a novel bovine chondrocytic cell
      line with differentiation potential.
AB  - In cartilage research bovine articular cartilage is used as an alternative to
      human tissue. However, animal material is subject to availability and primary
      cultures undergo senescence, limiting their use. Here we report the
      immortalization of primary bovine chondrocytes, which could be used as a
      surrogate for freshly isolated chondrocytes. Chondrocytes were isolated from
      cartilage explants and immortalized using 1.0 ug/ml benzo[alpha]pyrene. For 3
      dimensional culture, chondrocytes were resuspended in 0.5% low-melt agarose at
      high density (HD) and cultured for 24 h prior to determining changes in
      expression profile and morphology. A13/BACii chondrocytes acquired a 'flat'
      irregular morphology and a foetal-like cell volume (1,509.59 +/- 182.04 um(3)).
      The human cell line C-20/A4 showed a statistically similar volume and length to
      A13/BACii. Two-dimensional-cultured A13/BACii expressed elevated levels of type I
      collagen (col1), reduced levels of type II collagen (col2) compared to freshly
      isolated chondrocytes and an overall col2 to col1 expression ratio (col2:col1) of
      0.11 +/- 0.01. Upon 3-dimensional encapsulation, there was a significant rise in
      col2 expression in both A13/BACii and C-20/A4, suggesting a capacity for
      redifferentiation in both cell lines with a return of col2:col1 values of
      A13/BACii to values previously observed in primary chondrocytes. A13/BACii
      chondrocytes expressed aggrecan, matrix metalloproteinase (MMP)-3, MMP-9 and MMP
      13, further supporting indications of the differentiated phenotype. Here we
      report the creation of a novel chondrocytic cell line and demonstrate its strong
      potential for redifferentiation upon HD 3-dimensional encapsulation, providing an
      alternative to conventional dedifferentiated cell lines and primary culture.

PMID- 22398356
TI  - Testosterone synthesis in patients with 17beta-hydroxysteroid dehydrogenase 3
      deficiency.
AB  - 17beta-hydroxysteroid dehydrogenase 3 (17beta-HSD 3) deficiency is a rare cause
      of 46,XY disorders of sex development (DSD). At puberty, these patients
      experience a surge of androstenedione and also testosterone, leading to
      substantial virilization. The origin of testosterone synthesis in these patients
      remains elusive. We investigated the expression of the isoenzyme AKR1C3 (17beta
      HSD 5) in the testis and patient-derived genital skin fibroblasts (GSF) as well
      as the ability of GSF to synthesize testosterone. Supernatants of GSF cultures
      and serum samples of one patient before and after gonadectomy were analyzed by
      liquid and gas chromatography/mass spectrometry. The androgenic potential of GSF
      derived supernatants was also assessed by androgen receptor-mediated
      transactivation of a reporter gene in transiently transfected Chinese hamster
      ovary cells. Although AKR1C3 is expressed both in the testes and in GSF,
      androstenedione is rapidly metabolized and is not synthesized to testosterone.
      The transactivation potential of GSF supernatants towards the androgen receptor
      is declining within 48 h. However, under testis-equivalent androstenedione
      concentration, testosterone can be synthesized in 17beta-HSD 3-negative GSF.
      After gonadectomy, both androstenedione and testosterone decline rapidly in vivo.
      In 17beta-HSD 3 deficiency, relevant amounts of testosterone are synthesized most
      probably through AKR1C3 in the testis and not peripherally in GSF.

PMID- 22398358
TI  - Prevalence and profile of mild cognitive impairment in Parkinson's disease.
AB  - BACKGROUND/AIMS: The frequency of mild cognitive impairment (MCI) in Parkinson's
      disease (PD) ranges from 19 to 40%, and this is probably due to methodological
      differences between the studies. The aim of this study was to evaluate the
      frequency and profile of MCI in a large sample of nondemented PD subjects and
      neurologically healthy subjects (NHS). METHODS: A total of 872 subjects (582
      controls and 290 PD) were included. The association between MCI and PD was
      tested, using logistic regression models; odds ratios (OR) with 95% confidence
      intervals (CI) were calculated. RESULTS: Fifty-three percent of PD subjects and
      45% NHS met the criteria for MCI (p = 0.001). The PD subjects showed a higher
      frequency of nonamnestic MCI (naMCI), compared to NHS (23.8 vs. 14.4%, p <=
      0.0001). In comparison to NHS, PD was associated with a univariate OR of 1.9 (95%
      CI = 1.3-2.8) for naMCI, and this association was marginally significant after
      multiple comparisons (multivariate OR = 1.5, 95% CI = 0.96-2.3, p = 0.077).
      CONCLUSION: The association between PD and the impairment of nonmemory domains is
      probably due to frontal-subcortical involvement, which characterizes the disease.

PMID- 22398357
TI  - Hispanic parenting women in women-only versus mixed-gender drug treatment: a 10
      year prospective study.
AB  - The present study examined Hispanic substance-using parenting women treated in
      women-only (WO; n=126) versus mixed-gender (MG; n=853) programs and associated
      outcomes assessed 10 years after admission. Relative to other races/ethnicities
      of women admitted to the set of 40 California treatment programs in 2000-2002,
      Hispanic women were underrepresented in WO programs. Compared to those in MG
      programs, Hispanic women in WO programs demonstrated more severe treatment needs,
      indicated by their greater severity in drug and alcohol use, health and mental
      health problems, and criminal justice involvement at admission. They also had
      fewer economic resources (15% WO vs. 23% MG were employed, p<.05; 48% vs. 37% on
      public assistance, p<.05). Data based on administrative records covering 3 years
      pre-admission and 8 years post-admission showed that Hispanic women treated in WO
      programs had higher mental health service utilization over 8 years post-treatment
      admission, though no differences were found in trajectories of arrests and
      incarceration. In sum, long-term outcomes (in terms of criminal justice
      involvement) among Hispanic women in WO treatment were comparable to those in the
      MG treatment, despite greater service needs at admission. WO programs were able
      to engage more Hispanic women in use of mental health services. Future research
      should focus on factors limiting Hispanic women's participation in WO programs,
      which could suggest ways for improvement so as to benefit all Hispanic women in
      need of these special services.

PMID- 22398359
TI  - Objective evaluation of the correction by non-rigid registration of abdominal
      organ motion in low-dose 4D dynamic contrast-enhanced CT.
AB  - We objectively evaluate a straightforward registration method for correcting
      respiration-induced movement of abdominal organs in CT perfusion studies by
      measuring the distributions of alignment errors between corresponding landmark
      pairs. We introduce the concept and describe the advantages of using the surface
      normal component of distance between pairs of corresponding landmarks selected so
      that their surface normal is in one of the three coordinate axis directions, and
      show that such landmarks can be precisely placed with respect to the surface
      normal. Using a large population of landmark pairs on a substantial quantity of
      4D dynamic contrast-enhanced CT volume data, we quantify the average alignment
      errors of abdominal organs that remain uncorrected by registration.

PMID- 22398360
TI  - A sequential compression mechanical pump to prevent hypotension during elective
      cesarean section under spinal anesthesia.
AB  - BACKGROUND: Spinal anesthesia is a standard technique for cesarean section but
      can cause hypotension which may be related to venous pooling secondary to
      progesterone-induced decreases in vascular tone. This study investigated the use
      of a sequential compression mechanical pump with thigh-high sleeves with
      compression cycles timed to venous refilling. We hypothesized that this would
      recruit pooled venous blood from the lower limbs, maintain the central blood
      volume and thus decrease the incidence of hypotension. METHODS: One hundred
      parturients scheduled for elective cesarean section under spinal anesthesia were
      recruited and randomly assigned to use of either a mechanical pump (Group M) or
      control (Group C). A standardized protocol for co-hydration and anesthesia was
      followed. Hypotension, defined as a decrease in systolic blood pressure by >20%
      from baseline, was treated with 6-mg boluses of intravenous ephedrine. The
      incidence of hypotension was defined as the primary outcome. Median ephedrine
      requirement was taken as a measure of the severity of hypotension. RESULTS:
      Hypotension occurred in 12 of 47 (25.5%) patients in Group M compared to 27 of 45
      (60%) in Group C (P=0.001). The median [range] ephedrine dose was greater in
      Group C (12 [0-24]mg) compared to Group M (0 [0-12]mg) (P<0.001). There was no
      difference between groups in the time to onset of hypotension. CONCLUSION: The
      use of a sequential compression mechanical pump that detects venous refilling and
      cycles accordingly, reduced the incidence and severity of hypotension after
      spinal anesthesia for cesarean section.

PMID- 22398361
TI  - Shoulder-tip pain as an indicator of uterine rupture with a functioning epidural.

PMID- 22398362
TI  - Mental health risk factors for suicides in the US Army, 2007--8.
AB  - OBJECTIVE: Suicides among active duty US Army personnel have been increasing
      since 2004, surpassing comparable civilian rates in 2008. This analysis uses US
      military data to assess suicide rates for the 2-year period 2007--8, and examines
      relative risks (RR) of suicide associated with mental health disorders. METHODS:
      Historical trends of US Army suicides were assessed using 1977--2008 data from
      Army G-1 (Personnel). Suicide rates, RR and the 2000--8 trends of mental health
      disorders were calculated using data from the Defense Casualty Information
      Processing System and Defense Medical Surveillance System. RESULTS: A total of
      255 soldiers committed suicide in 2007--8 (2008 rate 20.2 per 100 000). Factors
      associated with higher suicide risk included male gender, lower enlisted rank and
      mental health disorders treated on an outpatient basis (RR 3.9), as well as a
      number of mental health disorders (mood disorders, anxiety disorders, post
      traumatic stress disorder, personality/psychotic disorders, substance-related
      disorders and adjustment disorder; RR range 4.7--24.5). Analysis of historical
      trends suggested that 25--50% of the suicides that occurred in 2008 might have
      been related to the major commitment of troops to combat beginning in 2003.
      CONCLUSIONS: The recent increase in suicides parallels an increase in the
      prevalence of mental disorders across the army. This finding suggests that
      increasing rates of clinically treated psychopathology are associated with
      increasing rates of suicides; these rates probably serve as sentinels for suicide
      risk in this population. Soldiers seeking treatment for mental disorders and
      substance abuse should be a focus for suicide prevention.

PMID- 22398363
TI  - Isotherm kinetics of Cr(III) removal by non-viable cells of Acinetobacter
      haemolyticus.
AB  - The potential use of non-viable biomass of a Gram negative bacterium i.e.
      Acinetobacter haemolyticus to remove Cr(III) species from aqueous environment was
      investigated. Highest Cr(III) removal of 198.80 mg g(-1) was obtained at pH 5,
      biomass dosage of 15 mg cell dry weight, initial Cr(III) of 100 mg L(-1) and 30
      min of contact time. The Langmuir and Freundlich models fit the experimental data
      (R(2)>0.95) while the kinetic data was best described using the pseudo second
      order kinetic model (R(2)>0.99). Cr(III) was successfully recovered from the
      bacterial biomass using either 1M of CH(3)COOH, HNO(3) or H(2)SO(4) with 90%
      recovery. TEM and FTIR suggested the involvement of amine, carboxyl, hydroxyl and
      phosphate groups during the biosorption of Cr(III) onto the cell surface of A.
      haemolyticus. A. haemolyticus was also capable to remove 79.87 mg g(-1) Cr(III)
      (around 22.75%) from raw leather tanning wastewater. This study demonstrates the
      potential of using A. haemolyticus as biosorbent to remove Cr(III) from both
      synthetic and industrial wastewater.

PMID- 22398364
TI  - Use of attenuated total reflectance Fourier transform infrared spectroscopy to
      study lactosylceramide and GD3 DMPC bilayers.
AB  - Attenuated total reflection Fourier transform infrared spectroscopy was used to
      monitor the formation of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC),
      DMPC: lactosylceramide, and DMPC: GD3 lipid bilayers onto a zinc selenide
      surface. Infrared absorption peak position, bandwidth, and intensity were all
      used to monitor the formation, acyl chain ordering, and chemical environment
      within each bilayer. The results from this study indicate that the addition of
      glycosphingolipids into a DMPC lipid bilayer introduces decreases in both, acyl
      chain ordering, and homogeneity within the bilayer. GD3:DMPC lipid bilayers
      possess lipid chain characteristics that are indiscernible from those present in
      the lactosylceramide:DMPC bilayer, while possessing different structural head
      groups, indicating that the head group has little influence on the underlying
      lipid structure. Differences in the phosphate hydration are, however, evident
      between the three types of bilayer, with phosphate hydration decreasing in the
      order LacCer:DMPC (1223.4 cm(-1))>DMPC only (1226 cm(-1))>GD3:DMPC (1229.6 cm(
      1)).

PMID- 22398365
TI  - Amphiphilic cylindrical copolypeptide brushes as potential nanocarriers for the
      simultaneous encapsulation of hydrophobic and cationic drugs.
AB  - Cylindrical copolypeptide brushes PLLF-g-(PLF-b-PLG) with poly(L-lysine-co-L
      phenylalanine) (PLLF) as the backbone and poly(L-phenylalanine)-b-poly(L-glutamic
      acid) (PLF-b-PLG) as the side chains have been synthesized and evaluated as drug
      delivery carriers. The synthesized copolypeptide brushes were characterized by
      (1)H NMR, gel permeation chromatography (GPC), and transmission electron
      microscopy (TEM). In aqueous solution, the copolypeptide brushes adopt
      cylindrical morphologies and resemble unimolecular polymeric micelles with a
      hydrophobic poly(L-phenylalanine) core and a hydrophilic poly(L-glutamate) shell.
      An encapsulation study demonstrated that these water soluble, biodegradable
      copolypeptide brushes encapsulate hydrophobic compounds and cationic hydrophilic
      guest molecules simultaneously. Furthermore, the encapsulated cationic model
      compounds exhibit a pH-responsive releasing property.

PMID- 22398366
TI  - Study on effect of lipophilic curcumin on sub-domain IIA site of human serum
      albumin during unfolded and refolded states: a synchronous fluorescence
      spectroscopic study.
AB  - Curcumin having pharmaceutical application as anti-oxidant, anti-inflammatory and
      anti-carcinogenic drug necessitates studying interaction of this molecule with
      native, unfolded and refolded state of human serum albumin (HSA), carrier protein
      in the blood. We proposed a simultaneous static and dynamic fluorescence
      quenching mechanism operating in the complex formation between HSA and curcumin.
      Location of curcumin in the close proximity of tryptophan with respect to
      tyrosine was further evident from the observation of two fold increase in rate of
      depletion of SFS intensity for tryptophan with respect to tyrosine in HSA in SFS
      spectrum. Alteration of SFS spectral peak position, electronic absorbance,
      fluorescence intensity and lifetime suggested chemical denaturation by urea
      expectedly unfold the protein molecule in the absence and presence of curcumin.
      Denatured HSA had similar fluorescence peak position and lifetime to that of L
      tryptophan in the polar environment. During unfolding of HSA the spectral change
      of tyrosine and tryptophan was resolved through synchronous fluorescence spectra
      at two different Deltalambda in absence and presence of curcumin. It is found
      that curcumin remained bound to unfolded state of HSA and facilitated the process
      by pushing tryptophan moiety to more polar environment in the unfolded state.
      Dilution of the denatured protein by phosphate buffer reversibly refolded the sub
      domain IIA, by also recovering fluorescence lifetime loss, but it was slow in the
      presence of curcumin. k(q) values indicate that curcumin-HSA complex is formed in
      the unfolded and refolded states as observed for native state.

PMID- 22398367
TI  - Effects of operating parameters on the efficiency of liposomal encapsulation of
      enzymes.
AB  - Encapsulation of active proteins in the hydrophilic core of vesicular liposomes
      is important for developing a therapeutic protein carrier system. The efficiency
      of liposomal encapsulation of proteins is generally low. A better understanding
      of the fundamental mechanisms of encapsulation is needed to increase this
      efficiency. In this study we investigated the effects of operating parameters
      such as phospholipid concentration, buffer pH and ionic strength, protein size
      and surface charge, and liposome size on the enzyme encapsulation yield. Four
      model enzymes of different molecular weights and isoelectric points (trypsin,
      horseradish peroxidase, enterokinase and hyaluronidase) were encapsulated into
      three different sized liposomes (125 nm, 194 nm, and 314 nm in mean diameter).
      Relatively inert and neutral DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine)
      was used as the main phospholipid in the liposomes. Size exclusion chromatography
      was used to separate the enzyme-encapsulated liposomes from the free enzyme, and
      the encapsulation yield was determined from the peak area. The encapsulation
      yield was generally low ranging from ca. 5% to 20%, and did not depend much on
      the molecular weight of the enzyme encapsulated. Larger liposomes had higher
      encapsulation yields. The electrostatic interaction between the phospholipid and
      enzyme was the most significant parameter in determining the encapsulation yield.
      Thus adjusting buffer pH and ionic strength and adding charged phospholipids to
      the liposome preparation to impart electric charge to the lipid bilayer could
      significantly improve the yield. This approach can be used to optimize the
      liposomal encapsulation of clinically significant proteins.

PMID- 22398370
TI  - T cells in helminth infection: the regulators and the regulated.
AB  - Helminth parasites survive through a combination of parasite longevity, repeated
      re-infection and selective immune suppression to prevent protective Th2
      responses. To counteract helminth-induced immunosuppression, and to induce long
      term immunological memory, understanding of the multiple regulatory pathways
      within the T cell compartment is needed. Extrinsic inhibition by regulatory T
      cells is a key element of Th2 suppression. In addition, Th2 cells in chronic
      regulatory environments become functionally impaired, indicating cell-intrinsic
      regulation, which compromises protective Th2 memory. We discuss these pathways
      and consider the potential for reversing unresponsiveness through stimulatory
      signals or replacement by new responder populations. Future vaccine or
      therapeutic strategies should aim to minimize extrinsic regulatory effects and
      simultaneously negate Th2 anergy to drive effector responses into a long-term
      functionally competent state.

PMID- 22398368
TI  - 5-Aza-2'-deoxycytidine induced growth inhibition of leukemia cells through
      modulating endogenous cholesterol biosynthesis.
AB  - 5-Aza-2'-deoxycytidine (5-Aza-CdR), a nucleoside analog that can inhibit DNA
      cytosine methylation, possesses potent antitumorigenic activities for myeloid
      disorders. Although 5-Aza-CdR is known to be incorporated into DNA and inhibit
      DNA (cytosine-5)-methyltransferases, the precise mechanisms underlying the drug's
      antineoplastic activity remain unclear. Here we utilized a mass spectrometry
      based quantitative proteomic method to analyze the 5-Aza-CdR-induced perturbation
      of protein expression in Jurkat-T cells at the global proteome scale. Among the ~
      2780 quantified proteins, 188 exhibited significant alteration in expression
      levels upon a 24-hr treatment with 5 MUm 5-Aza-CdR. In particular, we found that
      drug treatment led to substantially reduced expression of farnesyl diphosphate
      synthase (FDPS) and farnesyl diphosphate farnesyltransferase (FDFT1), two
      important enzymes involved in de novo cholesterol synthesis. Consistent with this
      finding, 5-Aza-CdR treatment of leukemia (Jurkat-T, K562 and HL60) and melanoma
      (WM-266-4) cells led to a marked decrease in cellular cholesterol content and
      pronounced growth inhibition, which could be rescued by externally added
      cholesterol. Exposure of these cells to 5-Aza-CdR also led to epigenetic
      reactivation of dipeptidyl peptidase 4 (DPP4) gene. Additionally, suppression of
      DPP4 expression with siRNA induced elevated protein levels of FDPS and FDFT1, and
      increased cholesterol biosynthesis in WM-266-4 cells. Together, the results from
      the present study revealed, for the first time, that 5-Aza-CdR exerts its
      cytotoxic effects in leukemia and melanoma cells through epigenetic reactivation
      of DPP4 gene and the resultant inhibition of cholesterol biosynthesis in these
      cells.

PMID- 22398372
TI  - The normoglycemic first-degree relatives of patients with type 2 diabetes
      mellitus have low circulating omentin-1 and adiponectin levels.
AB  - OBJECTIVE: It has been suggested that adipose-derived cytokines act as insulin
      sensitizers/insulin-mimetics and some others may induce insulin resistance. In
      order to elucidate the potential role of novel adipocytokines in the pre-diabetes
      states, circulating levels of novel adipocytokines were evaluated in first-degree
      relatives of subjects with type 2 diabetes mellitus (FDRs). METHOD: Serum omentin
      1, adiponectin and retinol-binding protein 4 (RBP4) levels were measured in 179
      subjects (90 glucose tolerant FDRs and 89 age- and sex-matched healthy controls)
      using enzyme-linked immunosorbent assay (ELISA) methods. RESULTS: There was no
      significant difference between the two groups regarding serum RBP4
      concentrations. However, serum omentin-1 (median [interquartile range], 6.18
      [4.06-11.52]ng/ml versus 10.50 [4.30-20.60]ng/ml, p=0.004) and adiponectin
      (mean+/-SD, 10.07+/-4.0 MUg/ml versus 20.66+/-8.12 MUg/ml, p<0.0001) levels were
      significantly lower in FDRs when compared with the controls. In multiple logistic
      regression analysis, FDRs showed a significant association with lower circulating
      omentin-1 and adiponectin levels, even after adjustments were made for age, sex,
      body mass index, blood pressure measures, and biochemical parameters including
      glucose status, lipid profile, insulin levels and HOMA-IR (OR=0.49, CI [0.30
      0.79]; p=0.004 and OR=0.74, CI [0.67-0.82]; p<0.0001, respectively). However,
      FDRs did not show a significant association with serum RBP4 levels in different
      models of regression analyses. CONCLUSIONS: The FDRs showed significant
      associations with lower omentin-1 and adiponectin levels. A potential role for
      these adipokines in the FDRs' increased risk of diabetes needs to be further
      elucidated.

PMID- 22398371
TI  - Pathogen-specific T cell depletion and reactivation of opportunistic pathogens in
      HIV infection.
AB  - During HIV infection, it is unclear why different opportunistic pathogens cause
      disease at different CD4 T cell count thresholds. Early work has shown that CD4 T
      cell depletion is influenced both by cellular activation status and expression of
      viral entry receptors. More recently, functional characteristics of the CD4 T
      cells, such as cytokine and chemokine production, have also been shown to
      influence cellular susceptibility to HIV. Here, we examine how functional
      differences in pathogen-specific CD4 T cells could lead to their differential
      loss during HIV infection. This may have implications for when different
      opportunistic infections occur, and a better understanding of the mechanisms for
      functional imprinting of antigen-specific T cells may lead to improvements in
      design of vaccines against HIV and opportunistic pathogens.

PMID- 22398373
TI  - Tocilizumab masks the clinical symptoms of systemic juvenile idiopathic arthritis
      associated macrophage activation syndrome: the diagnostic significance of
      interleukin-18 and interleukin-6.
AB  - Macrophage-activation syndrome (MAS) is a potentially life-threatening
      complication of systemic juvenile idiopathic arthritis (s-JIA). Tocilizumab
      (TCZ), a humanized anti-IL-6 receptor monoclonal antibody, is an effective
      cytokine inhibitor for the treatment of s-JIA. We described the clinical courses
      of five cases of MAS during TCZ therapy and demonstrated the need for monitoring
      serum interleukin (IL)-18 and IL-6 concentrations. Clinical symptoms of patients
      with s-JIA receiving TCZ were apparently mild compared to those not receiving
      TCZ. Furthermore, serum CRP concentrations never increased during TCZ therapy,
      even in MAS. Serum IL-6 concentrations increased during s-JIA flare-up and with
      the complication of infection. Serum IL-18 concentrations increased persistently
      before the other measures of disease activity. The clinical symptoms of MAS and s
      JIA could be masked during TCZ therapy; hence, monitoring serum concentrations of
      IL-18 and IL-6 is recommended for the evaluation of disease activity in s-JIA and
      to detect the complication of infection.

PMID- 22398374
TI  - Functional, morphologic, and molecular characterization of cold storage injury.
AB  - OBJECTIVE: Cold storage is used to preserve tissue for later transplantation.
      There is particular interest in prolonging cold storage time for transplantation
      purposes. To date, the mechanisms that contribute to vascular dysfunction in
      response to cold storage are poorly understood. The present study aims to
      characterize cold storage injury of blood vessels on functional and molecular
      levels. METHODS: To assess vessel function of mouse aorta, isometric force
      measurements were performed in a Mulvany myograph after cold storage at 4 degrees
      C for various intervals. Morphologic changes were judged by histologic analysis
      of aortic cross-sections. To characterize cold storage-induced alterations on RNA
      levels, microarray analysis with subsequent polymerase chain reaction analysis
      was performed. RESULTS: Cold storage for 2 days revealed significant impairment
      of vessel function with respect to potassium-induced vessel tone development and
      acetylcholine-induced vessel relaxation. Detailed analysis of acetylcholine
      mediated vascular response using specific pharmacologic blockers revealed that
      calcium-activated potassium channels seem to be impaired after 2 days of cold
      storage. At this point, no severe histologic changes (eg, elastic fiber
      disruption) were visible. RNA expression of 24 genes was significantly changed
      due to cold storage even after 2 hours. These include genes associated with
      vessel tone development (prostaglandin E(3) receptor), cardiovascular function
      (adiponectin), electron transport chain (uncoupling protein 1), or calcium
      signaling (protein kinase A regulatory subunit 2b). CONCLUSIONS: Long-term cold
      storage impairs vascular function, especially with respect to potassium signaling
      by calcium-dependent potassium channels. Microarray analysis confirmed impairment
      of pathways that are involved in calcium signaling and vascular function.
      Furthermore, various genes were significantly altered even after 2 hours,
      significantly before functional impairment was observed.

PMID- 22398375
TI  - Toward a dynamic biomarker model in Alzheimer's disease.
AB  - Biomarkers, both biological and imaging, are indicators of specific changes that
      characterize Alzheimer's disease (AD) progression in vivo. Knowing the precise
      relationship between biomarkers and disease severity would allow for accurate
      disease staging and possible forecasting of decline. Jack et al. suggested as an
      initial hypothesis that this relationship be sigmoidal; the objective of this
      article is to determine, using large-scale population data from ADNI, the precise
      shape of this association. We considered six different models (linear; quadratic;
      robust quadratic; local quadratic regression; penalized B-spline; and sigmoid)
      and used the Akaike Information Criterion to gauge how well these models compare
      in conforming to the data. We included 576 subjects (229 controls, 193 AD, and
      154 mild cognitive impairment subjects who converted to AD) from the ADNI study,
      for whom baseline data on cerebrospinal fluid amyloid-beta (Abeta)42,
      phosphorylated tau (p-tau), and total-tau (t-tau), hippocampal volumes, and FDG
      PET were available. Analysis of this cross-sectional dataset showed that a local
      quadratic regression model was 42% more likely than a sigmoid to be the best
      model for Abeta42. This ratio augments to 22% and 73% for Penalized B-Spline in
      the case of p-tau and t-tau, respectively; to 3500% for the linear model for FDG
      PET; and to 6700% for the Penalized B-Spline for hippocampal volumes.
      Preliminary, cross-sectional evidence therefore indicates that the shape of the
      association with disease severity is non-linear and differs between biomarkers.

PMID- 22398376
TI  - Amyloid-beta25-35 induces apolipoprotein D Synthesis and growth arrest in HT22
      hippocampal cells.
AB  - Apolipoprotein D (ApoD) is a secreted glycoprotein that is markedly induced in
      several pathological and stressful conditions in the nervous system. In the
      central nervous system, ApoD expression is upregulated during aging, after
      traumatic brain injury, and in several human neuropathologies such as Alzheimer's
      disease (AD), where it is found associated with amyloid-beta (Abeta) plaques.
      Recent studies have indicated that ApoD has an important function as a
      neuroprotective and antioxidant protein. The aim of this work is to study the
      effect of the peptide fragment Abeta25-35, which is believed to play a major role
      in the neurodegenerative process of AD, in ApoD expression in a mouse hippocampal
      cell line. In addition, we studied whether direct addition of exogenous human
      recombinant ApoD protein has neuroprotective effect against Abeta25-35 treatment
      on neuronal cells. Our results demonstrate that Abeta25-35 induces ApoD
      expression in hippocampal cells in response to stress-induced growth arrest. This
      observed relationship between Abeta and ApoD expression could explain the
      elevated levels of ApoD found in AD brain, where it may be a neuroprotective
      molecule in the course of AD, probably related to its lipid transport function or
      a direct antioxidant property. However, the addition of exogenous human
      recombinant ApoD does not exert any protective effect, most likely due to its
      major structural modifications.

PMID- 22398377
TI  - Defect-driven synthesis of self-assembled single crystal titanium nanowires via
      electrochemistry.
AB  - One-dimensional single crystal nanostructures have garnered much attention, from
      their low-dimensional physics to their technological uses, due to their unique
      properties and potential applications, from sensors to interconnects. There is an
      increasing interest in metallic titanium nanowires, yet their single crystal form
      has not been actualized. Vapor-liquid-solid (VLS) and template-assisted top-down
      methods are common means for nanowire synthesis; however, each has limitations
      with respect to nanowire composition and crystallinity. Here we show a simple
      electrochemical method to generate single crystal titanium nanowires on
      monocrystalline NiTi substrates. This work is a significant advance in addressing
      the challenge of growing single crystal titanium nanowires, which had been
      precluded by titanium's reactivity. Nanowires grew non-parallel to the surface
      and in a periodic arrangement along specific substrate directions; this behavior
      is attributed to a defect-driven mechanism. This synthesis technique ushers in
      new and rapid routes for single crystal metallic nanostructures, which have
      considerable implications for nanoscale electronics.

PMID- 22398378
TI  - [Terminal ileitis of uncommon etiology].

PMID- 22398379
TI  - Estrogen stimulates Th2 cytokine production and regulates the
      compartmentalisation of eosinophils during allergen challenge in a mouse model of
      asthma.
AB  - BACKGROUND: The observation that asthma becomes more prevalent following puberty
      in females suggests estrogen potentiates the development of this disease.
      However, most studies examining the role of estrogen in rodent models of asthma
      are complicated by their reliance on ovariectomised mice in which hormones other
      than estrogen are also attenuated. METHODS: We aimed to understand the influence
      of estrogen on allergic airway disease by using type I (tamoxifen) or type II
      (ICI 182,780) antagonists in female mice or delivering estradiol to male mice
      during aeroallergen challenge. RESULTS: The antagonists showed that estrogen
      promoted both the mobilisation of bone marrow eosinophils and egression of
      eosinophils to the airway lumen. These findings were corroborated in male mice
      treated with estradiol, which increased eosinophil numbers in both blood and
      airways. Estrogen stimulated goblet cell hyperplasia and baseline lung
      resistance, but had little effect on the number of eosinophils in the bronchial
      submucosa or methacholine-induced airway hyperreactivity. Estrogen receptor alpha
      was expressed by CD4+ T cells from allergic mice, and estrogen promoted the
      production of IL-5 and IL-13, and suppressed the production of the eicosanoid 12
      HETE by mediastinal lymph node cells. CONCLUSIONS: These data show that during
      aeroallergen challenge, estrogen stimulates Th2 cytokine production, which may be
      linked to its ability to suppress 12-HETE. Lung resistance at baseline, goblet
      cell hyperplasia and the compartmentalisation of eosinophils was also influenced
      by estrogen. However, estrogen does not play a major role in stimulating enhanced
      sensitivity to methacholine-induced lung resistance.

PMID- 22398380
TI  - Evaluation of multimeric tyrosine-O-sulfate as a cytoprotectant in an in vivo
      model of acute myocardial infarction in pigs.
AB  - OBJECTIVES: Intracoronary administration of glycosaminoglycan analogs, including
      the complement inhibitor dextran sulfate, attenuates myocardial
      ischemia/reperfusion injury (I/R injury). However, dextran sulfate has a distinct
      anticoagulatory effect, possibly limiting its use in specific situations in vivo.
      We therefore developed multimeric tyrosine sulfate (sTyr-PAA), a novel, minimally
      anticoagulatory, fully synthetic non-carbohydrate-containing polyacrylamide
      conjugate, for in vivo testing in an acute closed-chest porcine model of acute
      myocardial infarction. METHODS: Following balloon occlusion of the left anterior
      descending artery just after the first diagonal branch (60-minute ischemia), sTyr
      PAA (approx. 10 mg/kg bodyweight, fraction with strongest complement-inhibitory
      and minimal anticoagulatory properties, n = 11) or phosphate-buffered saline
      (controls, n = 9) was administered intracoronarily into ischemic myocardium prior
      to 120 min of reperfusion. RESULTS: sTyr-PAA significantly reduced infarct size
      (from 61.0 +/- 12.0% of the ischemic area at risk to 39.4 +/- 17.0%), plasma
      creatine kinase, local complement deposition and tissue factor upregulation,
      without affecting systemic coagulation. Protection was associated with
      significantly reduced myocardial neutrophil extravasation and translated into a
      significant improvement of ejection fraction and left ventricular enddiastolic
      pressure. CONCLUSIONS: sTyr-PAA protected significantly against myocardial I/R
      injury without substantially affecting systemic coagulation. Local intravascular
      sTyr-PAA administration may prove advantageous in situations where bleeding
      complications are likely or are to be avoided at all costs.

PMID- 22398381
TI  - Ultrasonic pretreatment for lipase-catalyed synthesis of phytosterol esters with
      different acyl donors.
AB  - This study is focused on the enzymatic esterification of phytosterols with
      different acyl donors to produce the corresponding phytosterol esters catalyzed
      by Canadia sp. 99-125 lipase under ultrasound irradiation. An ultrasonic
      frequency of 35 kHz, power of 200 W and time of 1h was determined to guarantee
      satisfactory degree of esterification and lipase activity. The influence of
      temperature, substrates concentration and molar ratio was investigated
      subsequently. The optimum production was achieved in isooctane system at 60
      degrees C with phytosterol concentration of 150 MUmol/mL and phytosterol to fatty
      acid molar ratio of 1:1.5, resulting in a phytosterol esters conversion of above
      85.7% in short reaction time (8h). Phytosterols esters could also be converted in
      high yields to the corresponding long-chain acyl esters via transesterification
      with triacylglycerols (above 90.3%) under ultrasound irradiation. In optimum
      conditions, the overall esterification reaction rate using the ultrasonic
      pretreatment process was above 2-fold than that of mechanical stirring process
      without damage the lipase activity.

PMID- 22398382
TI  - Ultrasound assisted synthesis of tetrahydrobenzo[c]xanthene-11-ones using CAN as
      catalyst.
AB  - Tetrahydrobenzo[c]xanthenes-11-ones was synthesized by a three component reaction
      of alpha-naphthol, aromatic aldehyde and dimedone. Ceric ammonium nitrate acts as
      a suitable eco-friendly catalyst for this method. Shorter reaction duration, mild
      reaction condition and low cost make this protocol more effective.

PMID- 22398383
TI  - Rapid and sensitive determination of hydroxyproline in dairy products using
      micellar electrokinetic chromatography with laser-induced fluorescence detection.
AB  - Many reports have focused on the determination of hydroxyproline (Hyp) in blood
      plasma, urine sample, meat and meat products, however, there are few concerned
      with the Hyp assay in dairy products for food quality assurance up to now. In
      this paper, we described a sensitive and automated approach for the determination
      of Hyp in milk powder, liquid milk, milk drink and soymilk powder samples by
      micellar electrokinetic chromatography (MEKC) based on in-capillary
      derivatization for the first time. Under the optimal conditions, derivatization
      and separation procedure could be completed within 7 min and the detection limit
      for Hyp was 1.6+/-0.5 ng mL(-1). Comparing with the existing alternatives, the
      present method exhibited some relevant advantages, including full automation,
      satisfactory sensitivity, and short analysis time for Hyp assay in dairy
      products.

PMID- 22398384
TI  - Predictions of comprehensive two-dimensional gas chromatography separations from
      isothermal data.
AB  - Two-dimensional retention times and peak widths in temperature programmed
      comprehensive two-dimensional gas chromatography were predicted using a
      theoretical model developed from experimental data obtained under isothermal
      conditions. A Matlab program was written to calculate the following parameters:
      dead time (t(M)), elution temperature (T(e)), retention time (t(R)), hold-up
      width (w(M)) and peak width (w(R)). The two-dimensional retention times of a
      sample mixture that contained n-alkanes and polyaromatic hydrocarbons (PAHs) were
      predicted and were observed to be in excellent agreement with experimentally
      determined values. The relative deviation between the model and the experimental
      data was less than 2 and 7% for the primary and secondary retention times,
      respectively. The relative deviation of peak width was less than 7 and 10% in the
      primary and secondary dimensions, respectively. The advantage of this model was
      its simplicity, informed entirely from experimental data, with no reliance on
      theoretical parameters. This prediction model would be useful for optimizing
      GC*GC separation conditions and for confirming compound identifications of
      components that are chromatographically resolved but that have nearly identical
      mass spectra.

PMID- 22398385
TI  - Selective isolation of G-quadruplexes by affinity chromatography.
AB  - G-quadruplex (G4) is a characteristic secondary structure of nucleic acids
      containing repetitive tandem guanines. G4-forming sequences are found prevalent
      in the human genome by bioinformatics analysis. Accumulating evidence has
      suggested that G4s are involved in many biological processes. Selective isolation
      of G4s would be an effective tool in the study of G4s. In this paper, we prepared
      four affinity matrixes using hemin or a perylene derivative (N,N'-Bis-(2
      (amino)ethyl)-3,4,9,10-perylenetetracarboxylic acid diimide, Pery01) as ligand,
      and investigated the retention behaviors of different G4s on these matrixes. Our
      experimental results suggest that the pi-pi stacking interaction between ligand
      and G-tetrad plays a key role in the selective isolation of G4s, whereas the
      electrostatic interaction between DNA and matrix causes the nonspecific binding.
      One matrix prepared by immobilizing Pery01 on polyglycidylmethacrylate (PGMA)
      beads through an aminocaproic acid spacer exhibits good selectivity for parallel
      structure G4s and has been successfully used to directly isolate a spiked
      parallel G4 from plasma.

PMID- 22398386
TI  - Identity and eating disorders (IDEA): a questionnaire evaluating identity and
      embodiment in eating disorder patients.
AB  - BACKGROUND: In this paper we tested the hypothesis that persons with eating
      disorders (EDs) are affected by disturbances of the way they experience their own
      body (embodiment) and shape their personal identity, assuming that the various
      kinds of anomalies of eating behavior are consequences thereof. SAMPLING AND
      METHODS: We developed and validated a new self-reported questionnaire named IDEA
      (IDentity and EAting disorders), which was administered to 147 ED patients and
      187 healthy controls. Test-retest reliability, internal consistency,
      psychopathological correlates, and concurrent validity were evaluated. A factor
      analysis was performed to verify the distribution of items into subscales.
      RESULTS: The questionnaire showed good test-retest reliability, and internal
      consistency. IDEA scores were specifically associated with ED psychopathology,
      and they did not show any correlation with sociodemographic and general clinical
      variables. Four factors were extracted, which were related to the following
      phenomena: 'feeling oneself only through the gaze of the other and defining
      oneself only through the evaluation of the other', 'feeling oneself only through
      objective measures', 'feeling extraneous from one's own body', and 'feeling
      oneself through starvation'. CONCLUSIONS: IDEA represents a multidimensional,
      brief, versatile, easy-to-perform instrument for clinical evaluation, assessing
      abnormalities in lived corporeality, and of personal identity, which appeared to
      be specifically associated with the core features of ED psychopathology. The main
      limitations of the study are the cross-sectional design. Also, it is impossible
      to ascertain whether the domains we assessed are specific traits of patients with
      EDs, or state-related features. To answer this question, a longitudinal study is
      needed.

PMID- 22398387
TI  - Prognostic value of 48-hour ambulatory blood pressure measurement and
      cardiovascular mortality in hemodialysis patients.
AB  - BACKGROUND: Hypertension is common and contributes to high cardiovascular
      morbidity and mortality in hemodialysis (HD) patients. It is unknown which blood
      pressure (BP) better defines the influence on cardiovascular mortality. The
      purpose of our study was to analyze the relationship between various BP
      measurements, traditional risk factors, markers of asymptomatic atherosclerosis
      [left ventricular mass (LVM), carotid intima media thickness (IMT)], and
      cardiovascular mortality in HD patients. METHODS: Seventy-three patients (44
      males and 29 females; mean age: 54.2 years) were included. BP was measured before
      and after HD and 48-hour ambulatory blood pressure monitoring (ABPM) was
      performed. Using sonography, the LVM index and carotid IMT were measured.
      RESULTS: During a follow-up period up to 3,664 days, 28 patients died - 16 of
      them from cardiovascular causes. In a Cox regression model, which included age,
      gender, smoking, diabetes, sensitive C-reactive protein, albumin, hemoglobin,
      troponin T, low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol, triglycerides, calcium, phosphorus, carotid IMT, and LVM index, only
      48-hour systolic ABPM (p = 0.037) and 48-hour diastolic ABPM (p = 0.006) turned
      out to be independent predictors of cardiovascular death. CONCLUSION: Only 48
      hour ABPM and not single BP measurements before or after HD were associated with
      cardiovascular mortality in HD patients.

PMID- 22398388
TI  - Impairment of heme synthesis in myelin as potential trigger of multiple
      sclerosis.
AB  - The pathogenesis of multiple sclerosis (MS), a disease characterized by
      demyelination and subsequent axonal degeneration, is as yet unknown. Also, the
      nature of the disease is as yet not established, since doubts have been cast on
      its autoimmune origin. Genetic and environmental factors have been implied in MS,
      leading to the idea of an overall multifactorial origin. An unexpected role in
      energizing the axon has been reported for myelin, supposed to be the site of
      consumption of most of oxygen in brain. Myelin would be able to perform oxidative
      phosphorylation to supply the axons with ATP, thanks to the expression therein of
      mitochondrial F(o)F(1)-ATP synthase, and respiratory chains. Interestingly,
      myelin expresses the pathway of heme synthesis, hence of cytochromes, that rely
      on heme group, in turn depending on Fe availability. Poisoning by these
      pollutants shares the common characteristic to bring about demyelination both in
      animal models and in man. Carbon monoxide (CO) and lead poisoning which cause
      functional imbalance of the heme group, as well as of heme synthesis, cause
      myelin damage. On the other hand, a lack of essential metals such as iron and
      copper, produces dramatic myelin decrease. Myelin is a primary target, of iron
      shortage, indicating that in myelin Fe-dependent processes are more active than
      in other tissues. The predominant spread of MS in industrialized countries where
      pollution by heavy metals, and CO poisoning is widespread, suggests a
      relationship among toxic action of metal pollutants and MS. According to the
      present hypothesis, MS can be primarily triggered by environmental factors acting
      on a genetic susceptibility, while the immune response may be a consequence of a
      primary oxidative damage due to reactive oxygen species produced consequently to
      an imbalance of cytochromes and respiratory chains in the sheath.

PMID- 22398389
TI  - Harmful immune reactions during acute myocardial infarction.
AB  - Acute coronary syndrome, including myocardial infarction, can occur as a result
      of ischaemia-reperfusion injury caused by acute occlusion of the coronary
      vessel/s following the rupture of an atherosclerotic plaque. Superimposed
      thrombosis at the lesion obstructs blood supply to the myocardium causing
      myocardial necrosis and ischaemic inflammation. Although not fully described,
      researchers believe that this process is initiated by a dysfunctional endothelium
      that activates the nearby leukocytes in the blood stream, thus attracting them to
      the arterial wall and initiating a cascade of complex mechanisms that lead to
      myocardial infarction. Interestingly, this process is two sided as the leaking
      soluble factors from a damaged and/or necrotic myocardium enter the systemic
      circulation, activating the innate and adaptive cell-mediated immune responses,
      which include increasing cytotoxic mediators. We hypothesize that this unwanted
      side effect of increase in proinflammatory mediators can lead to harmful systemic
      immune reactions directed towards various dysfunctional endothelia. Additionally,
      a strong inflammatory response, caused by myocardial damage, can impair
      ventricular function, on top of baseline necrosis. To evaluate this hypothesis,
      we propose to use in vivo tests to measure endothelial dysfunction, as well as
      ventricular dysfunction by ultrasound methods, and their correlation with
      immunological and/or biochemical parameters. These tests will be useful in
      assessing the risk and therapeutic outcome in patients with acute coronary
      syndrome.

PMID- 22398390
TI  - Differences in demographic, behavioral, and biological variables between those
      with valid and invalid accelerometry data: implications for generalizability.
AB  - BACKGROUND: The exclusion of participants with invalid accelerometry data (IAD)
      may lead to biased results and/or lack of generalizability in large population
      studies. The purpose of this study was to investigate whether demographic,
      behavioral, and biological differences occur between those with IAD and valid
      accelerometry data (VAD) among adults using a representative sample of the
      civilian noninstitutionalized U.S. population. METHODS: Ambulatory participants
      from NHANES (2003-2004) who were 20-85 years of age were included in the current
      study and wore an ActiGraph 7164 accelerometer for 7 days. A "valid person" was
      defined as those with 4 or more days of at least 10+ hrs of monitoring per day.
      Among adults (20-85 yrs), 3088 participants provided VAD and 987 provided IAD.
      Demographic, behavioral, and biological information were obtained from the
      household interview or from data obtained in a mobile examination center.
      RESULTS: Differences were observed in age, BMI, ethnicity, education, smoking
      status, marital status, use of street drugs, current health status, HDL
      cholesterol, C-reactive protein, self-reported vigorous physical activity, and
      plasma glucose levels between those with VAD and IAD. CONCLUSIONS: Investigators
      should take into consideration the potential cut-off bias in interpreting results
      based on data that excludes IAD participants.

PMID- 22398391
TI  - Retromers in Alzheimer's disease.
AB  - Amyloid-beta peptide (Abeta), the key pathogenic agent in Alzheimer's disease
      (AD), is released after sequential proteolytic cleavage of the transmembrane
      amyloid precursor protein (APP). beta-Site APP-cleaving enzyme 1 (BACE1) cleaves
      APP in early endosomes, and the cause of increased BACE cleavage of APP in AD is
      not fully resolved yet. It has been proposed that perturbed intracellular
      trafficking of APP, which leads to prolonged residence time in early endosomes,
      influences Abeta production and hence the risk for AD. Retromers are a family of
      proteins that mediate the retrieval of transmembrane proteins from the endosomes
      to the trans-Golgi network. Misregulation of retromers or retromer-associated
      proteins influences endosomal localization of APP/BACE1. Here we review the role
      of retromers in the amyloidogenic processing of APP and their pathogenic role in
      AD.

PMID- 22398392
TI  - Improvement of spread-out Bragg peak flatness for a carbon-ion beam by the use of
      a ridge filter with a ripple filter.
AB  - We have developed a novel design method of ridge filters for carbon-ion therapy
      using a broad-beam delivery system to improve the flatness of a biologically
      effective dose in the spread-out Bragg peak (SOBP). So far, the flatness of the
      SOBP is limited to about +/-5% for carbon beams since the weight control of
      component Bragg curves composing the SOBP is difficult. This difficulty arises
      from using a large number of ridge-bar steps (e.g. about 100 for a SOBP width of
      60 mm) required to form the SOBP for the pristine Bragg curve with an extremely
      sharp distal falloff. Instead of using a single ridge filter, we introduce a
      ripple filter to broaden the Bragg peak so that the number of ridge-bar steps can
      be reduced to about 30 for SOBP with of 60 mm for the ridge filter designed for
      the broadened Bragg peak. Thus we can manufacture the ridge filter more
      accurately and then attain a better flatness of the SOBP due to well-controlled
      weights of the component Bragg curves. We placed the ripple filter on the same
      frame of the ridge filter and arranged the direction of the ripple-filter-bar
      array perpendicular to that of the ridge-filter-bar array. We applied this method
      to a 290 MeV u(-1) carbon-ion beam in Heavy Ion Medical Accelerator in Chiba and
      verified the effectiveness by measurements.

PMID- 22398393
TI  - 25-hydroxyvitamin D and physical and cognitive performance in older people with
      chronic conditions.
AB  - INTRODUCTION: Recently, the relationship between vitamin D deficiency and various
      pathologies as well as functional decline has been reported. OBJECTIVES: The aim
      of the study was to assess the relationship between 25-hydroxyvitamin D, 25(OH)D,
      levels and functional status in elderly patients. PATIENTS AND METHODS: Mean age
      of 140 participants (women, 67.1%) was 79.64 +/-6.99 years. The study had a cross
      sectional design. Physical performance was measured using the handgrip strength,
      Timed Up and Go, single-leg stance, and tandem stance tests, as well as a balance
      platform. Cognition was evaluated with the Abbreviated Mental Test Score (AMTS),
      while functional status with the Basic Activities of Daily Living (ADL) and
      Instrumental Activities of Daily Living (IADL) scales. Plasma 25(OH)D levels were
      measured. RESULTS: Less able patients (worse results in all tests) had
      significantly lower 25(OH)D levels. Subjects with 25(OH)D levels within the 3rd
      tertile had a higher AMTS score and handgrip strength; they swayed less on the
      balance platform and performed better in the IADL. In multivariate logistic
      regression analysis, 25(OH)D levels of 23.26-47.75 nmol/l were associated with
      increased odds of cognitive impairment (odds ratio [OR], 3.17; 95% confidence
      interval [CI], 1.04-9.68; P = 0.04), but also with less lateral sway (OR, 0.24;
      95% CI, 0.09-0.64; P = 0.005). Plasma 25(OH)D levels above 47.75 nmol/l were
      associated with better performance in the tandem stance test (OR, 0.14; 95% CI,
      0.04-0.52; P = 0.003) and further decreased lateral sway (OR, 0.27; 95% CI, 0.10
      0.77; P = 0.01). CONCLUSIONS: In elderly people with comorbid conditions, 25(OH)D
      levels were not associated with handgrip strength, but were associated with
      balance and cognitive function. These associations as well as high prevalence of
      vitamin D deficiency necessitate further research evaluating the effect of
      vitamin D supplementation on the functional status in elderly people.

PMID- 22398394
TI  - The fetal brain provides a raison d'etre for the evolution of new human genes.

PMID- 22398395
TI  - Enhancement of temporal resolution and BOLD sensitivity in real-time fMRI using
      multi-slab echo-volumar imaging.
AB  - In this study, a new approach to high-speed fMRI using multi-slab echo-volumar
      imaging (EVI) is developed that minimizes geometrical image distortion and
      spatial blurring, and enables nonaliased sampling of physiological signal
      fluctuation to increase BOLD sensitivity compared to conventional echo-planar
      imaging (EPI). Real-time fMRI using whole brain 4-slab EVI with 286 ms temporal
      resolution (4mm isotropic voxel size) and partial brain 2-slab EVI with 136 ms
      temporal resolution (4*4*6 mm(3) voxel size) was performed on a clinical 3 Tesla
      MRI scanner equipped with 12-channel head coil. Four-slab EVI of visual and motor
      tasks significantly increased mean (visual: 96%, motor: 66%) and maximum t-score
      (visual: 263%, motor: 124%) and mean (visual: 59%, motor: 131%) and maximum
      (visual: 29%, motor: 67%) BOLD signal amplitude compared with EPI. Time domain
      moving average filtering (2s width) to suppress physiological noise from cardiac
      and respiratory fluctuations further improved mean (visual: 196%, motor: 140%)
      and maximum (visual: 384%, motor: 200%) t-scores and increased extents of
      activation (visual: 73%, motor: 70%) compared to EPI. Similar sensitivity
      enhancement, which is attributed to high sampling rate at only moderately reduced
      temporal signal-to-noise ratio (mean: -52%) and longer sampling of the BOLD
      effect in the echo-time domain compared to EPI, was measured in auditory cortex.
      Two-slab EVI further improved temporal resolution for measuring task-related
      activation and enabled mapping of five major resting state networks (RSNs) in
      individual subjects in 5 min scans. The bilateral sensorimotor, the default mode
      and the occipital RSNs were detectable in time frames as short as 75 s. In
      conclusion, the high sampling rate of real-time multi-slab EVI significantly
      improves sensitivity for studying the temporal dynamics of hemodynamic responses
      and for characterizing functional networks at high field strength in short
      measurement times.

PMID- 22398396
TI  - An algorithmic method for functionally defining regions of interest in the
      ventral visual pathway.
AB  - In a widely used functional magnetic resonance imaging (fMRI) data analysis
      method, functional regions of interest (fROIs) are handpicked in each participant
      using macroanatomic landmarks as guides, and the response of these regions to new
      conditions is then measured. A key limitation of this standard handpicked fROI
      method is the subjectivity of decisions about which clusters of activated voxels
      should be treated as the particular fROI in question in each subject. Here we
      apply the Group-Constrained Subject-Specific (GSS) method for defining fROIs,
      recently developed for identifying language fROIs (Fedorenko et al., 2010), to
      algorithmically identify fourteen well-studied category-selective regions of the
      ventral visual pathway (Kanwisher, 2010). We show that this method retains the
      benefit of defining fROIs in individual subjects without the subjectivity
      inherent in the traditional handpicked fROI approach. The tools necessary for
      using this method are available on our website
      (http://web.mit.edu/bcs/nklab/GSS.shtml).

PMID- 22398397
TI  - Approach in glucocorticoid-induced osteoporosis prevention: results from the
      Italian multicenter observational EGEO study.
AB  - Glucocorticoid-induced osteoporosis (GIO) is the most frequent cause of secondary
      osteoporosis. GIO is linked to glucocorticoids (GC) daily assumption with maximum
      effect within first months of treatment and decreasing to basal levels as the
      therapy is discontinued. In Italy, primary prevention of GIO is suggested when GC
      therapy (prednisone >5 mg/day or equivalent) is taken for longer than 3 months.
      Lazio GISMO (Italian Group for Study and Diagnosis of Bone Metabolism Diseases)
      group organized the GC and Osteoporosis Epidemiology study (EGEO) to evaluate
      physician's approach in preventing GIO. The study involved 19 osteoporosis
      centers. Patients taking long-term GC therapy were recruited and information
      collected: medical history and anthropometric data, GC therapy, primary disease,
      physician's specialty, osteopororosis screening, and pharmacological
      intervention. The study included 1334 patients. Mean age was 63 +/- 13 yr; 243
      (18%) patients had a history of falls from standing position in the previous 12
      months, 78 (35%) vertebral fractures, 91 (41%) fractures other than vertebral, 27
      (12%) femoral fractures, and 27 (12%) multiple sites fractures. The molecules of
      GC more often prescribed were prednisone and 6-metil prednisolone. One thousand
      and forty patients (78%) were taking GC for more than 6 months. GC therapy was
      prescribed more frequently by rheumatologists (62%). Antiosteoporotic drugs for
      GIO prevention were prescribed in 431 patients (32%). Among the patients, only
      27% (360) received calcium and vitamin D supplements, and 39% (319) treated by
      rheumatologists received anti-resorptive drugs. In conclusion, our data show that
      in Italy, as already described elsewhere, only a small subpopulation of GC
      treated patients was supported by an anti-osteoporotic therapy, indicating the
      need to further stimulate awareness of both patients and specialists, prescribing
      GC therapy, to an appropriate and prompt GIO prevention.

PMID- 22398398
TI  - Fas expression in renal cell carcinoma accurately predicts patient survival after
      radical nephrectomy.
AB  - OBJECTIVES: To investigate Fas, Fas ligand (FasL) and Bcl-2 expression, which are
      considered to be important apoptotic regulatory factors in renal cell carcinomas
      (RCCs). PATIENTS AND METHODS: mRNA quantification and immunohistochemistry
      allowed for the determination of the expression of these three factors in
      surgically resected tumors from 82 patients with RCC. The correlation of protein
      and gene expression with more than 10 years of survival data following
      nephrectomy (along with clinical and pathologic parameters) was analyzed using
      uni- and multivariate statistical models. RESULTS: A significantly poorer outcome
      was observed in patients with tumors expressing high levels of Fas mRNA in the
      multivariate analysis (p = 0.0002). In addition, patient survival was
      significantly worse in FasL mRNA-positive tumor cases when compared with FasL
      mRNA-negative cases (p = 0.0345). Ten cases relapsed more than 5 years after
      nephrectomy. Among them, the tumors of 8 cases (80%) did not express FasL mRNA.
      Analysis of Bcl-2 did not show statistical significance of Bcl-2 expression as a
      prognostic indicator. CONCLUSIONS: The data suggest that pronounced Fas
      expression is a surrogate biomarker of active cancer cell proliferation. Given
      the FasL tumor counterattack theory, FasL overexpression in RCC may be one of the
      host immune deficiencies, consequently leading to poor prognosis.

PMID- 22398399
TI  - Common pathways for growth and for plasticity.
AB  - Cell growth and differentiation in developing tissues are, at first impression,
      quite different endeavors from readjusting synaptic strength during activity
      dependent synaptic plasticity in mature neurons. Nevertheless, it is becoming
      increasingly clear that these two distinct processes share multiple intracellular
      signaling events. How these common pathways result in cell division (during
      proliferation), large-scale cellular remodeling (during differentiation) or
      synapse-specific changes (during synaptic plasticity) is only starting to be
      elucidated. Here we review the latest findings on two prototypical examples of
      these shared mechanisms: the Ras-PI3K pathway and the intracellular signaling
      elicited by neural cell adhesion molecules interacting with growth factor
      receptors.

PMID- 22398400
TI  - Human disorders of axon guidance.
AB  - Axon pathfinding is essential for the establishment of proper neuronal
      connections during development. Advances in neuroimaging and genomic
      technologies, coupled with animal modeling, are leading to the identification of
      an increasing number of human disorders that result from aberrant axonal wiring.
      In this review, we summarize the recent clinical, genetic and molecular advances
      with regard to three human disorders of axon guidance: Horizontal gaze palsy with
      progressive scoliosis, Congenital mirror movements, and Congenital fibrosis of
      the extraocular muscles, Type III.

PMID- 22398402
TI  - Alexithymia and severe psychopathology: a study on psychiatric inpatients.
AB  - BACKGROUND: The influence of severe psychopathology on alexithymic features has
      been poorly studied. This study aimed at investigating whether alexithymia is
      affected by the presence of psychosis and the severity of psychopathology.
      SAMPLING AND METHODS: 199 consecutive adult psychiatric inpatients, 60 of whom
      received a Structured Clinical Interview for DSM-IV Axis I diagnosis of psychotic
      disorder, were administered the 20-item Toronto Alexithymia Scale (TAS-20) and
      the 24-item Brief Psychiatric Rating Scale (BPRS). A random sample of 50 patients
      was reassessed at discharge. For all analyses, the Holm-Bonferroni correction was
      applied when appropriate to account for multiple testing. RESULTS: The TAS-20
      showed good internal consistency, acceptable relative stability, and good
      absolute stability both in patients with and without a psychotic disorder.
      Internal consistency and relative stability were higher in nonpsychotic than in
      psychotic patients. Mean TAS-20 score at admission did not differ between
      psychotic and nonpsychotic patients, and the TAS-20 score showed only a
      nonsignificant correlation (rho = 0.26) with BPRS score. Alexithymia at discharge
      was mostly explained (60%) by alexithymia at admission, while it was only
      modestly explained (4%) by BPRS scores at admission and discharge, with the
      latter being the only significant predictor. Changes in BPRS scores between
      admission and discharge explained a nonsignificant proportion (16%) of changes in
      TAS-20 scores and a moderate (21%) proportion of changes in difficulty
      identifying feelings. CONCLUSION: Despite some limitations, these findings
      suggest that the severity of psychopathology and the presence of a psychotic
      disorder only modestly influence alexithymic characteristics, and that the TAS-20
      may provide a reliable assessment of alexithymia in patients with severe
      psychopathology, except the most severely impaired ones.

PMID- 22398403
TI  - Abstracts of VII Congresso Sindem, Italian Association for the study of Dementia
      linked to the Italian Neurological Society (SIN). March 22-24, 2012. Naples,
      Italy.

PMID- 22398404
TI  - Dinuclear complexes of tetravalent cerium in an aqueous perchloric acid solution.
AB  - Primary aquo species of tetravalent cerium (Ce(IV)) in perchloric acid has been
      identified as a single oxo-bridging dinuclear complex, not a mononuclear one, by
      extended X-ray absorption fine structure (EXAFS) spectroscopy combined with
      density functional theory (DFT) calculations.

PMID- 22398405
TI  - Early life interventions to prevent allergy in the offspring: the role of
      maternal immunization and postnatal mucosal allergen exposure.
AB  - BACKGROUND: Childhood allergy is influenced by maternal factors and allergen
      exposure in early life, but the factors that determine the development of allergy
      and tolerance are unknown. Therefore, we compared the effects of two early life
      interventions, i.e. maternal allergen immunization and postnatal intranasal
      allergen exposure, as well as a combination of both treatments on allergic
      responses in the offspring. METHODS: Female mice were immunized with ovalbumin
      (OVA) or vehicle during pregnancy. After birth, half the offspring from each
      group were exposed intranasally to low doses of OVA or vehicle weekly for 5 weeks
      before intraperitoneal immunization with OVA. RESULTS: Maternal immunization
      reduced OVA-specific IgE and IgG1, but increased IgG2a and T(H)2 cytokine
      responses in the offspring after immunization. Postnatal intranasal OVA exposure
      similarly reduced both IgE and IgG1, but also spleen cell numbers and cytokine
      secretion. Following airway challenges of the offspring, IgE and airway
      inflammation were suppressed only by intranasal exposure, but not by maternal
      immunization, the effect of which also waned with age. Differential gene
      expression in the spleen of offspring supported that IgE suppression by the two
      interventions was caused by different mechanisms. Despite this, tolerance
      development after mucosal exposure was obtained in the offspring of immunized
      dams. CONCLUSIONS: The study suggests that prevention of allergy is possible if
      initiated in early life, and early mucosal allergen exposure may play a
      protective role independent of the maternal immune responses.

PMID- 22398406
TI  - Biopolymer gel matrix as acellular scaffold for enhanced dermal tissue
      regeneration.
AB  - Biological grafts have drawbacks such as donor scarcity, disease transmission,
      tissue infection, while the scaffolds of either collagen or chitosan fabrics fail
      to become part of the tissue at the wound site, though they favor the formation
      of connective tissue matrix. This study developed a novel composite consisting of
      the combination of atelocollagen and chitosan in order to provide a biodegradable
      molecular matrix in gel form as a biomimetic surface for cell attachment, to
      promote the wound healing in excision wounds. We found that the topical
      application of biopolymer composite on the wound promoted cell proliferation,
      migration and collagen deposition overtime. The enhanced cellular activity in the
      collagen-chitosan treated wound tissue was also assed by increased levels of
      Platelet derived growth factor (PDGF) and Nerve growth factor (NGF) associated
      with elevated levels of antioxidants and decreased level of lipid peroxidation.
      The acellular matrix-like topical application material is designed to guide the
      eventual re-establishment of an anatomically normal skin. The results of this
      study demonstrate the feasibility of multi-cell regeneration on a molecular
      system that mimics tissue engineering in vivo.

PMID- 22398407
TI  - Visible light-harvesting perylenebisimide-fullerene (C60) dyads with
      bidirectional "ping-pong" energy transfer as triplet photosensitizers for
      photooxidation of 1,5-dihydroxynaphthalene.
AB  - Visible light-harvesting perylenebisimide (PBI)-C(60) dyads were prepared as
      organic triplet photosensitizers for photooxidation of 1,5-dihydroxynaphthalene
      and the efficiency of the dyads is 6-fold of the conventional Ir(III) complex
      triplet photosensitizer.

PMID- 22398408
TI  - Exposure to bisphenol A is associated with low-grade albuminuria in Chinese
      adults.
AB  - Bisphenol A is an industrial chemical widely used in plastic products with a
      consequent exposure to humans. To assess whether exposure to bisphenol A is
      associated with renal disease, we searched for low-grade albuminuria in 3055
      Chinese adults in the Shanghai metropolitan area aged 40 years or older. Using a
      value for urinary albumin-to-creatinine ratios <30 mg/g, we examined its
      association with urinary bisphenol A. Participants in the highest compared to the
      lowest quartile of urinary bisphenol A concentrations were significantly more
      likely to have low-grade albuminuria. Multivariate stepwise linear regression
      analysis, adjusted for potential confounding factors, showed that urinary
      bisphenol A was an independent determinant of the urinary albumin-to-creatinine
      ratio significantly associated with an increased risk of low-grade albuminuria
      with an adjusted odds ratio of 1.23 for the highest compared to the lowest
      concentration quartiles. This association was not modified by conventional risk
      factors such as age, gender, smoking, alcohol consumption, body mass index,
      hypertension, diabetes, and the estimated glomerular filtration rate. There was
      no significant relationship between bisphenol A and combined micro- and
      macroalbuminuria. Thus, our study lends support to a potential relation between
      bisphenol A exposure and an increased risk of low-grade albuminuria.

PMID- 22398409
TI  - Podocyte EphB4 signaling helps recovery from glomerular injury.
AB  - Eph receptor tyrosine kinases and their ligands (ephrins) have a pivotal role in
      the homeostasis of many adult organs and are widely expressed in the kidney.
      Glomerular diseases beginning with mesangiolysis can recover, with podocytes
      having a critical role in this healing process. We studied here the role of Eph
      signaling in glomerular disease recovery following mesangiolytic Thy1.1 nephritis
      in rats. EphB4 and ephrinBs were expressed in healthy glomerular podocytes and
      were upregulated during Thy1.1 nephritis, with EphB4 strongly phosphorylated
      around day 9. Treatment with NPV-BHG712, an inhibitor of EphB4 phosphorylation,
      did not cause glomerular changes in control animals. Nephritic animals treated
      with vehicle did not have morphological evidence of podocyte injury or loss;
      however, application of this inhibitor to nephritic rats induced glomerular
      microaneurysms, podocyte damage, and loss. Prolonged NPV-BHG712 treatment
      resulted in increased albuminuria and dysregulated mesangial recovery.
      Additionally, NPV-BHG712 inhibited capillary repair by intussusceptive
      angiogenesis (an alternative to sprouting angiogenesis), indicating a previously
      unrecognized role of podocytes in regulating intussusceptive vessel splitting.
      Thus, our results identify EphB4 signaling as a pathway allowing podocytes to
      survive transient capillary collapse during glomerular disease.

PMID- 22398411
TI  - Untreated cavitated dentine lesions: impact on children's quality of life.
AB  - The aim of the present investigation was to assess the impact of dental caries
      prevalence and the consequences of untreated cavitated dentine lesions on quality
      of life of 6- and 7-year-old Brazilian children. A total of 826 schoolchildren
      were assessed using ICDAS and pufa (to score consequences of dental caries on
      soft tissues) indices. History of extraction and toothache was recorded. Oral
      health-related quality of life was assessed using the Brazilian version of the
      Early Childhood Oral Health Impact Scale (B-ECOHIS). A multiple logistic
      regression model was used to analyze the relationship between the prevalence of
      dentine carious lesions, pufa, history of extraction and toothache with the B
      ECOHIS scores. A total of 587 questionnaires were analyzed. The prevalence of
      cavitated dentine lesions and pufa was 74.8 and 26.2%, respectively. Some 21.8%
      of children reported toothache and 9.2% had had at least one tooth extraction.
      The chance (OR) for children with cavitated dentine lesions, pufa >=1, history of
      extraction and toothache of having higher B-ECOHIS scores than those not affected
      was 1.90 (95% CI: 1.18-3.06), 6.26 (95% CI: 3.63-10.83), 6.87 (95% CI: 2.75
      17.16) and 3.68 (95% CI: 2.12-6.39), respectively. Children's quality of life was
      negatively influenced by untreated cavitated dentine lesions and their
      consequences.

PMID- 22398410
TI  - Bioavailable vitamin D is more tightly linked to mineral metabolism than total
      vitamin D in incident hemodialysis patients.
AB  - Prior studies showed conflicting results regarding the association between 25
      hydroxyvitamin D (25(OH)D) levels and mineral metabolism in end-stage renal
      disease. In order to determine whether the bioavailable vitamin D (that fraction
      not bound to vitamin D-binding protein) associates more strongly with measures of
      mineral metabolism than total levels, we identified 94 patients with previously
      measured 25(OH)D and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) from a cohort of
      incident hemodialysis patients. Vitamin D-binding protein was measured from
      stored serum samples. Bioavailable 25(OH)D and 1,25(OH)(2)D were determined using
      previously validated formulae. Associations with demographic factors and measures
      of mineral metabolism were examined. When compared with whites, black patients
      had lower levels of total, but not bioavailable, 25(OH)D. Bioavailable, but not
      total, 25(OH)D and 1,25(OH)(2)D were each significantly correlated with serum
      calcium. In univariate and multivariate regression analysis, only bioavailable
      25(OH)D was significantly associated with parathyroid hormone levels. Hence,
      bioavailable vitamin D levels are better correlated with measures of mineral
      metabolism than total levels in patients on hemodialysis.

PMID- 22398412
TI  - Correlation between the resistive index values of renal and orbital arteries.
AB  - BACKGROUND: Resistive index (RI) is an indirect measurement of blood flow
      resistance that can be used to evaluate vascular damage. AIMS: The purpose of
      this study is to evaluate the association between RI values of orbital and
      intrarenal arteries by means of Doppler ultrasonography (US). METHODS: We
      evaluated 103 diabetic patients. As a control group, 30 subjects were examined.
      The patients were divided into two groups. Group 1 consisted of patients with
      urinary albumin excretion (UAE) <300 mg/day and estimated glomerular filtration
      rate (eGFR) levels >90 ml/min (n = 50); Group 2 had a UAE >300 mg/day and/or eGFR
      levels between 89 and 60 ml/min (n = 53). The association between RI values
      obtained with Doppler US of the ophthalmic artery, central retinal artery,
      posterior ciliary artery and intrarenal arteries were calculated. RESULTS: Both
      orbital and intrarenal arterial RI values in Group 1 and Group 2 were higher than
      the control group (p = 0.001); furthermore, values were higher in Group 2 than in
      Group 1 (p = 0.0004/0.029/0.036, p = 0.016, respectively). A positive correlation
      was found between orbital and intrarenal arterial RI values in Group 2 (r =
      0.475, 0.285, 0.363, p < 0.01, respectively). CONCLUSION: Both orbital and renal
      arterial RI values were shown to be higher than the control group. Further, a
      trend towards higher RI values was observed with renal disease. RI may be useful
      as one of the markers for early diagnosis and follow-up of diabetic nephropathy
      and retinopathy.

PMID- 22398413
TI  - A cyclodextrin host-guest recognition approach to a label-free electrochemical
      DNA hybridization biosensor.
AB  - A novel label-free electrochemical DNA hybridization biosensor using a beta
      cyclodextrin/poly(N-acetylaniline)/carbon nanotube composite modified screen
      printed electrode (CD/PNAANI/CNT/SPE) has been developed. The proposed DNA
      hybridization biosensor relies on the intrinsic oxidation signals of guanine (G)
      and adenine (A) from single-stranded DNA entered into the cyclodextrin (CD)
      cavity. Due to the binding of G and A bases to complementary cytosine and thymine
      bases in dsDNA, the signals obtained for ssDNA were much higher than that of
      dsDNA. The synergistic effect of the multi-walled carbon nanotubes provides a
      significantly enhanced voltammetric signal, and the CD encapsulation effect makes
      anodic peaks of G and A shift to less positive potentials than that at the bare
      SPE. The peak heights of G and A signals are dependent on both the number of the
      respective bases in oligonucleotides and the concentration of the target DNA
      sequences. Hybridization of complementary strands was monitored through the
      measurements of oxidation signal of purine bases, which enabled the detection of
      target sequences from 0.01 to 1.02 nmol MUl(-1) with the detection limit of
      target DNA as low as 5.0 pmol MUl(-1) (S/N = 3). Implementation of label-free and
      homogeneous electrochemical hybridization detection constitutes an important step
      toward low-cost, simple, highly sensitive and accurate DNA assay. Discrimination
      between complementary, noncomplementary, and two-base mismatch targets was easily
      accomplished using the proposed electrode.

PMID- 22398414
TI  - Liberty or death; don't tread on me.
AB  - Many jurisdictions require cyclists to wear bicycle helmets. The UK is currently
      not one of these. However, an increasing number of interest groups, including the
      British Medical Association, want to change the status quo. They argue that
      mandatory cycle helmet laws will reduce the incidence of head injuries and that
      this will be both good for cyclists (because they will suffer fewer head
      injuries) and good for society (because the burden of having to treat cyclists
      suffering from head injuries will be reduced). In this paper we argue against
      this position. We suggest that cycle helmets may not be especially effective in
      reducing head injuries and we suggest that the imposition of such a restrictive
      law would violate people's freedom and reduce their autonomy. We also argue that
      those who accept such a restrictive law would be committed to supporting further
      legislation which would force many other groups - including pedestrians - to take
      fewer risks with their health. We conclude that cycle helmet legislation should
      not be enacted in the UK unless, perhaps, it is restricted to children.

PMID- 22398415
TI  - Accuracy of algorithms for detection of atrial fibrillation from short duration
      beat interval recordings.
AB  - Atrial fibrillation (AF) is characterised by highly variable beat intervals. The
      aims of the study were to assess the accuracy of AF detection algorithms from
      short analysis durations and to validate prospectively the accuracy on a large
      community-based cohort of elderly subjects. Three algorithms for AF detection
      were evaluated: coefficient of variation (CV), mean successive difference (Delta)
      and coefficient of sample entropy (COSEn), using two databases of beat interval
      recordings: 167 recordings of 300 s duration for a range of rhythms acquired in a
      hospital setting and 2130 recordings of 10s duration acquired in the community.
      Using the longer recordings receiver operating characteristic (ROC) analysis was
      used to identify optimal algorithm thresholds and to evaluate analysis durations
      ranging from 5s to 60s. An ROC area of 93% was obtained at recording duration of
      60s but remained above 90% for durations as low as 5s. Prospective analysis on
      the 2130 recordings gave AF detector sensitivities from 90.5% (CV and Delta) to
      95.2% (COSEn), specificities from 89.3% (Delta) to 93.4% (COSEn) and accuracy
      from 89.3% (Delta) to 93.4% (COSEn), not significantly different to those
      obtained on the initial database. AF detection algorithms are effective for short
      analysis durations, offering the prospect of a simple and rapid diagnostic test
      based on beat intervals alone.

PMID- 22398416
TI  - Resources as a protective factor for negative outcomes of frailty in elderly
      people.
AB  - BACKGROUND: Although frailty is often conceptualized in terms of deficits, the
      level of frailty can be perceived as a complex interplay between deficits and
      resources. OBJECTIVE: We studied whether resources such as educational level,
      financial situation, and living-alone status moderate the negative effects of
      deficits on two potentially adverse consequences of frailty: self-perceived
      health and receiving professional care. METHODS: Logistic regression analysis was
      performed with data from a cross-sectional survey, designed by the public health
      service in the south of the Netherlands. The questionnaire was completed by a
      representative sample of people aged 70 and over (n = 5,559). Interaction effects
      between deficits (multimorbidity, difficulty performing ADLs, psychological
      distress, loneliness) and resources (educational level, financial situation,
      living-alone status) were studied in relation to self-perceived health and
      receiving professional care. RESULTS: We found that in males the effect of
      difficulty in performing ADLs on self-perceived health was modified by
      educational level (p < 0.05, indicating that difficulty in performing ADLs is
      more strongly related to moderate/bad self-perceived health for those with higher
      education). In females, the effect of psychological distress on self-perceived
      health was modified by educational level (p < 0.05, indicating that suffering
      from psychological distress is more strongly related to moderate/bad self
      perceived health for those with higher education) and the effect of difficulty in
      performing ADLs on receiving professional care was modified by living-alone
      status (p < 0.05, indicating that difficulty in performing ADLs was more strongly
      related to receiving professional care for those women who lived alone).
      CONCLUSIONS: Resources moderate the impact of personal deficits on self-perceived
      health and receiving professional care. Some frail people seem to be more
      vulnerable as they lack resources such as a high level of education. This should
      be taken into account in deciding when elderly people are at risk of negative
      outcomes of frailty and is therefore important for health professionals and
      policy-makers.

PMID- 22398417
TI  - Oral anticoagulation use by patients with atrial fibrillation in Germany.
      Adherence to guidelines, causes of anticoagulation under-use and its clinical
      outcomes, based on claims-data of 183,448 patients.
AB  - Atrial fibrillation (AF) is the most common significant cardiac rhythm disorder.
      Oral anticoagulation (OAC) is recommended by guidelines in the presence of a
      moderate to high risk of stroke. Based on an analysis of claims-based data, the
      aim of this contribution is to quantify the stroke-risk dependent OAC utilisation
      profile of German AF patients as well as the possible causes and the associated
      clinical outcomes of OAC under-use. Our data set was derived from two large
      mandatory German medical insurance funds. Risk stratification of patients was
      based on the CHADS2-score and the CHA2DS2-VASc-score. Two different scenarios
      were constructed to deal with factors potentially disfavouring OAC use. Causes of
      OAC under-use and its clinical consequences were analysed using multivariate
      analysis. Observation year was 2008. A total of 183,448 AF patients met the
      inclusion criteria. This represents an AF prevalence of 2.21%. The average CHADS2
      score was 2.8 (CHA2DS2-VASc-score: 4.3). On between 40.5 and 48.7% of the
      observed patient-days, there was no antithrombotic protection by OAC, other
      anticoagulants or aspirin. Older female patients with a high number of
      comorbidities had a higher risk of OAC under-use. Patients who had already
      experienced a thromboembolic event had a lower risk of OAC under-use. In the
      observation year, 3,367 patients experienced a stroke (incidence rate 1.8%). In
      our multi-level Poisson random effects estimate, OAC use decreases the stroke
      rate by almost 80% (IRR 0.236). In conclusion, OAC under-use is widespread in the
      German market. It is associated with severe clinical consequences.

PMID- 22398419
TI  - Effect of secondary hyperparathyroidism treatment with cinacalcet on selected
      adipokines and markers of endothelial injury in hemodialysis patients: a
      preliminary report.
AB  - INTRODUCTION:  Disturbances in endothelial function, adipokines, and mineral
      metabolism due to secondary hyperparathyroidism (SHPT) shorten the lifespan in
      hemodialysis (HD) patients. OBJECTIVES:  The aim of the study was to evaluate the
      effect of SHPT treatment with cinacalcet on selected adipokines and markers of
      endothelial injury in HD patients. PATIENTS AND METHODS:  Soluble thrombomodulin
      (sTM), E-selectin, leptin, and adiponectin levels were measured in patients with
      SHPT at baseline and at 6 months of cinacalcet treatment. RESULTS:  A total of 18
      patients completed the study. SHPT treatment with cinacalcet decreased calcium,
      phosphate, and intact parathormone (iPTH) levels; however, no significant changes
      in sTM, E-selectin, leptin, or adiponectin were observed. iPTH levels after
      treatment correlated with age (r = -0.51, P =   0.031), mean cinacalcet dose (r =
      0.65, P = 0.004), as well as baseline calcium (r = 0.65 P = 0.003), iPTH (r =
      0.59, P = 0.01), E-selectin (r = 0.56, P = 0.016), and leptin (r = -0.49, P =
      0.039). CONCLUSIONS:  Cinacalcet treatment does not affect the markers of
      endothelial function and selected adipokines. Effectiveness of treatment may be
      modulated by E-selectin and leptin.

PMID- 22398418
TI  - Energy cost of common activities in children and adolescents.
AB  - BACKGROUND: The Compendium of Energy Expenditures for Youth assigns MET values to
      a wide range of activities. However, only 35% of activity MET values were derived
      from energy cost data measured in youth; the remaining activities were estimated
      from adult values. PURPOSE: To determine the energy cost of common activities
      performed by children and adolescents and compare these data to similar
      activities reported in the compendium. METHODS: Thirty-two children (8-11 years
      old) and 28 adolescents (12-16 years) completed 4 locomotion activities on a
      treadmill (TRD) and 5 age-specific activities of daily living (ADL). Oxygen
      consumption was measured using a portable metabolic analyzer. RESULTS: In
      children, measured METs were significantly lower than compendium METs for 3
      activities [basketball, bike riding, and Wii tennis (1.1-3.5 METs lower)]. In
      adolescents, measured METs were significantly lower than compendium METs for 4
      ADLs [basketball, bike riding, board games, and Wii tennis (0.3-2.5 METs lower)]
      and 3 TRDs [2.24 m . s(-1), 1.56 m . s(-1), and 1.34 m . s(-1) (0.4-0.8 METs
      lower)]. CONCLUSION: The Compendium of Energy Expenditures for Youth is an
      invaluable resource to applied researchers. Inclusion of empirically derived data
      would improve the validity of the Compendium of Energy Expenditures for Youth.

PMID- 22398420
TI  - Microwave-assisted synthesis of gold nanoparticles self-assembled into self
      supported superstructures.
AB  - Passivated gold nanoparticles were synthesized through a microwave-assisted
      process in a two-phase system, in the presence of 1-dodecanethiol. An average
      particle size of 1.8 nm of the gold nanoparticles obtained and 0.35 S.D. was
      determined through HRTEM and STEM analysis. It was observed that these
      nanoparticles spontaneously self-assemble into self-supported superstructures of
      1 MUm in diameter avg and 400 nm thickness, yielding an off-white powder which
      can be handled as a simple powder. XRD analysis indicates that n-alkanethiol
      molecules used as a passivating compound, besides protecting against crystal
      growth, interact to form cubic ordered arrays between the nanoparticles. This
      interaction leads to the superstructure formation, with an average distance
      between nanoparticles in the array, of 3.56 nm. Theoretical calculations and
      molecular dynamics simulations were performed to analyze the resulting structure.

PMID- 22398421
TI  - Early stages of motor skill learning and the specific relevance of the cortical
      motor system--a combined behavioural training and theta burst TMS study.
AB  - PURPOSE: To examine whether motor performance and motor learning in healthy
      subjects can be segregated into a number of distinct motor abilities which are
      linked to intact processing in different motor-related brain regions (M1, S1,
      SMA, PMC) early during learning. METHODS: Seven young healthy subjects trained in
      eight motor arm tasks (Arm Ability Training, AAT) once a day for 5 days using
      their left non-dominant arm. Except for day 1 (baseline), training was performed
      before and after applying an inhibitory form of repetitive transcranial magnetic
      stimulation (cTBS, continuous theta burst) to either M1, S1, SMA, or PMC.
      RESULTS: A principal component analysis of the motor behaviour data suggested
      four independent motor abilities: aiming, speed, steadiness, and visuomotor
      tracking. AAT induced substantial motor learning across abilities. Within session
      effects of cTBS revealed that activity in primary somatosensory cortex (S1) was
      relevant for motor performance and learning across all tasks whereas M1 was
      specifically involved in rapid tapping movements, PMC in ballistic arm navigation
      in extra-personal space; performance on a non-trained motor tasks was not
      affected by cTBS. CONCLUSIONS: Cortical sensory and motor areas including S1, M1,
      and PMC functionally contribute to early motor learning in a differential manner
      across motor abilities.

PMID- 22398422
TI  - [Assessment of airway inflammation by exhaled gas and exhaled breath condensate].

PMID- 22398423
TI  - [Objective measurements of disease severity and diagnostic confirmation in atopic
      dermatitis and urticaria].

PMID- 22398424
TI  - [Approach to the pathogenesis of allergic diseases: findings from cohort studies
      in Chiba].

PMID- 22398425
TI  - [Mechanisms regulating or dysregulating toll-like receptors in the steady or
      disease state].

PMID- 22398426
TI  - [Changes in treatment, symptoms and QOL of pediatric asthma patients at different
      ages for 7 years in Tochigi].
AB  - BACKGROUND: A 7-year analysis of pediatric asthma in Tochigi was performed with
      the aim of improvement of future treatment. METHODS: Self-administered
      questionnaires were completed by pediatric asthma patients and their parents who
      visited pediatric clinics or hospitals in Tochigi at the same period of year in
      2002, 2006, and 2008. Changes in asthma symptoms and in the QOL of the patients
      and their parents were analyzed. Data on the background and treatment of the
      patients were obtained from doctors. RESULTS: The questionnaires were answered by
      1487, 1058, and 1014 patients or parents in 2002, 2006, and 2008, respectively.
      The results showed significant increases in the use of ICS and LTRA (p< 0.001,
      for each.) and significant decreases in the use of theophylline, DSCG, and LABA
      (p< 0.001, for each.). Frequency of wheezing, cough and sputum were significantly
      reduced in all age groups (p< 0.01, for each.). There were significant reductions
      of frequency of wheezing in patients under 2 years old; in wheezing and cough in
      patients aged 2-5 years old; and in wheezing, cough and sputum in patients aged 6
      15 years old (p< 0.05 for each.). The QOL of the patients and their parents was
      significantly improved in all age groups (p< 0.05 for each.). CONCLUSION: These
      findings suggest that increased use of anti-inflammatory agents such as LTRA and
      ICS have contributed to a reduction in asthma symptoms and an improvement in the
      QOL of the pediatric patients and their parents, but more widespread use of these
      agents are still needed for residual uncontrolled asthma patients.

PMID- 22398427
TI  - [Diagnosis and consultation rates of allergic diseases in 11-year old
      schoolchildren, and usefulness of allergy screening test at school].
AB  - BACKGROUND: Even though allergic diseases continue to increase among children, it
      is unclear as to how many of these children are receiving appropriate medical
      care. PURPOSE: To establish the number of schoolchildren being diagnosed and
      receiving consultation for their allergic diseases and to determine if their
      disease status is associated with their total and allergen-specific IgE levels.
      Additionally, the study examined whether providing information on the total and
      allergen-specific IgE levels to the parents resulted in improvement of the
      medical care their children received. METHODS: A total of 618 out of the 627
      (94.5%) parents of 11-year-old schoolchildren living in Ohmi-Hachiman City,
      Shiga, Japan, answered a questionnaire designed to determine the presence of
      allergic diseases (bronchial asthma, atopic dermatitis, allergic rhinitis, and
      allergic conjunctivitis) and the status of medical care in their children. Levels
      of total IgE, mite-specific IgE, and three pollen-specific IgEs were measured at
      the same time that the questionnaires were filled out. Information from the
      questionnaires was used to analyze the relationships between the questionnaire
      data and IgE levels. After parents were given the IgE results, medical
      consultations were recommended for those children having allergic symptoms and
      positive allergen-specific IgEs. One year after providing the information, a
      follow-up survey was performed to determine whether parents took any actions in
      response to their children's test results. RESULTS: The mean total IgE level was
      138 IU/ml, with a total of 62.8% of the children sensitized to one or more
      allergens. Even among those without any allergic disease, 49.2% or the children
      sensitized to one or more allergens. In children with bronchial asthma, diagnosis
      and consultation rates were 100% and 81%, respectively. However, the diagnosis
      and consultation rates among those with other types of allergic diseases were
      significantly lower, ranging from 44 to 88% for diagnosis and 28 to 52% for
      consultation. A total of 63% of the parents with children having allergic
      diseases indicated they undertook further efforts designed to improve their
      child's allergy disease symptoms after they were informed of the total and
      allergen-specific IgE levels. CONCLUSION: Results of the present survey
      demonstrated that significant numbers of children with atopic dermatitis,
      allergic rhinitis or allergic conjunctivitis were not given appropriate medical
      care. In order to conclusively determine whether total and allergen-specific IgE
      screening at schools is useful in ensuring that children receive appropriate
      medical care, further evaluations will need to be conducted.

PMID- 22398428
TI  - [Pollen dispersion of Cryptomeria japonica and Cupressaceae in Ito city during 10
      years].
AB  - BACKGROUND: For a period of 10 years, ending in 2010, the authors investigated
      atmospheric pollen dispersion of Cryptomeria japonica and Cupressaceae in Ito
      City. We expect this investigation useful in treating patients with pollen
      allergy. METHODS: We set up a Durham sampler on a rooftop of the three-story
      building in Ito City and counted atmospheric pollen day by day. The results and
      the local weather conditions were treated statistically on the computer program
      Microsoft Excel. RESULTS: During the 10 years, in average, initial pollen was
      observed at January 3; pollen began to release was observed at February 6; final
      pollen was observed at May 12. The spring seasonal total pollen counts was 5683
      grain/cm2. This pollen counts and the previous early winter seasonal pollen
      counts were correlated statistically. The pollen counts were related with the
      local weather conditions significantly. CONCLUSION: The investigations of the
      atmospheric pollen dispersion of Cryptomeria japonica and Cupressaceae and the
      weather conditions in the local area are useful to treat patients with the pollen
      allergy.

PMID- 22398429
TI  - Application of nanosized MCM-41 to fabrication of a nanostructured
      electrochemical sensor for the simultaneous determination of levodopa and
      carbidopa.
AB  - A novel carbon paste electrode modified with nanosized mesoporous MCM-41 was
      prepared, and used as an electrochemical sensor to study the electro oxidation of
      levodopa (LD), carbidopa (CD) and their mixtures. Using differential pulse
      voltammetry (DPV), a highly selective and simultaneous determination of LD and CD
      has been explored at the modified electrode. The electrochemical sensor displayed
      a good resolving function for the overlapping voltammetric responses of LD and CD
      into two separate peaks with a potential difference of 370 mV. DPV peak currents
      of LD increased linearly with concentration over the 0.13 MUM to 1250.00 MUM
      range and exhibited a detection limit of 0.072 MUM. Also, the proposed
      electrochemical sensor was used for the determination of LD and CD in some real
      samples, using the standard addition method.

PMID- 22398430
TI  - Cdk5 phosphorylates a component of the HDAC complex and regulates histone
      acetylation during neuronal cell death.
AB  - Cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase family,
      is critical for regulating neural development and neuronal survival.
      Dysregulation of Cdk5 is associated with abnormal expression of cell cycle
      related proteins during neuronal apoptosis. We have previously found that p35, a
      Cdk5 activator, interacts with mSds3, an integral component of the histone
      deacetylase complex in vitro, suggesting a functional role of Cdk5 in gene
      regulation through modulation of chromatin integrity. In this study, we further
      demonstrate that Cdk5-dependent phosphorylation of mSds3 at Ser228 occurs in
      mouse brain nuclei. The expression of mSds3 protein and its interaction with Cdk5
      activators is developmentally regulated in the mouse brain. Importantly, our
      findings suggest that the ability of Cdk5 to regulate activity deprivation
      induced apoptosis of cerebellar granule neurons is likely mediated by the
      regulation of histone acetylation. Suppression of Cdk5 not only attenuates the
      induction of histone H3 acetylation and the aberrant upregulation of cyclin
      proteins in neurons after activity deprivation, but also results in protection of
      neurons against apoptotic cell death. Taken together, our findings suggest that
      Cdk5 regulates neuronal survival by precise epigenetic control through modulation
      of histone acetylation.

PMID- 22398431
TI  - Dabigatran etexilate (Pradaxa(r)) for preventing warfarin-induced skin necrosis
      in a patient with severe protein C deficiency.

PMID- 22398432
TI  - Aerobic capacity testing with inactive individuals: the role of subjective
      experience.
AB  - BACKGROUND: Maximal oxygen uptake (VO2max), an assessment of cardiorespiratory
      fitness, is regularly used as the primary outcome in exercise interventions. Many
      criteria have been suggested for validating such tests-most commonly, a plateau
      in oxygen consumption. The current study investigated the proportion of inactive
      individuals who reached a plateau in oxygen uptake and who achieved a valid test
      as assessed by secondary criteria (RERmax >= 1.1; RPEmax >= 18; age predicted
      HRmax +/-10bpm), and the correlates of a successful plateau or achievement of
      secondary criteria during a VO2max session. METHODS: Participants (n = 240) were
      inactive individuals who completed VO2max assessments using an incremental
      treadmill test. We explored physical, behavioral, and motivational factors as
      predictors of meeting criteria for meeting a valid test. RESULTS: Approximately
      59% of the sample achieved plateau using absolute (increase of VO2 of 150ml O2 or
      less) and 37% achieved plateau using relative (increase of VO2 of 1.5ml/kg O2 or
      less) criteria. Being male, having a higher BMI, a greater waist-to-hip ratio,
      and increased self-efficacy were associated with lower odds of achieving an
      absolute plateau, whereas none of these factors predicted odds of achieving
      relative plateau. CONCLUSION: Findings raise questions about the validity of
      commonly used criteria with less active populations.

PMID- 22398433
TI  - Specific job anxiety in comparison to general psychosomatic symptoms at
      admission, discharge and six months after psychosomatic inpatient treatment.
AB  - OBJECTIVE: Job anxiety is a severe problem in many patients with chronic mental
      disorders, as it usually results in specific participation problems in the
      workplace and long-term sick leave. The aim of this study was to explore the
      development of sick leave in dependence on general psychosomatic complaints and
      job anxiety from admission to a psychosomatic inpatient treatment until 6 months
      after discharge. METHOD: A convenience sample of 91 patients, suffering from
      multiple mental disorders, filled in self-rating questionnaires on job anxiety
      (Job Anxiety Scale) and on general psychosomatic symptom load (Symptom Checklist
      90-Revised) at the beginning, the end, and 6 months after discharge from an
      inpatient psychosomatic treatment. Additionally, sick leave status and employment
      status were assessed before and 6 months after the treatment. RESULTS: 15.4% of
      91 patients were on sick leave before inpatient treatment and at follow-up (SS
      group), 20.9% were fit for work at intake and follow-up (FF group), 6.6% were fit
      for work initially and on sick leave later (FS group), and 57.1% on sick leave
      first and working at follow-up (SF group). In regard to general psychosomatic
      complaints, there were initially high scores on the SCL, a marked reduction
      during inpatient treatment, and a bouncing back to initial levels at follow-up
      for all 4 patient groups. SS and FS patients showed the highest scores at intake
      and follow-up. Concerning job anxiety, SS patients had the highest scores at all
      three assessments, while FF patients had significantly lower scores, with only
      low variation between assessments. SF patients started with comparatively high
      scores of job anxiety, which even increased before reentering work, but decreased
      in the follow-up period when they were confronted with work again. FS patients
      started low (like the FF patients) at intake, reduced their job anxiety further
      till discharge, but increased to higher scores at follow-up. CONCLUSIONS: General
      psychosomatic symptom load and job anxiety show a different course during
      treatment and are differently related to sick leave. General psychosomatic
      symptom load can be understood as a measure of the degree of the chronic illness
      status, whereas job anxiety reflects specific additional context-related
      problems, i.e. problems with work. A core finding is that job anxiety is related
      to work avoidance, but work exposure may reduce job anxiety. This has direct
      consequences for putting patients on sick leave or not.

PMID- 22398435
TI  - Erratum to: Randomized clinical trial on preoperative radiotherapy 25 Gy in
      rectal cancer-treatment results at 5 year follow-up.

PMID- 22398434
TI  - Outcome of overlap anastomosis using a linear stapler after laparoscopic total
      and proximal gastrectomy.
AB  - BACKGROUND: Recently, novel intracorporeal esophagojejunostomy using a linear
      stapler after laparoscopic total gastrectomy (LTG) was reported and termed as the
      overlap method. In this study, we evaluated the feasibility and safety of the
      overlap method for esophagojejunostomy or esophagogastrostomy after LTG or
      laparoscopic proximal gastrectomy (LPG), respectively. METHODS: Twenty-five
      patients underwent anastomosis using a linear stapler during esophagojejunostomy
      and esophagogastrostomy after LTG and LPG, respectively. Clinicopathological data
      and surgical outcomes were evaluated. RESULTS: The average surgical duration for
      LTG was 236.8 min compared with 224.1 min for LPG. Postoperative complications
      were observed in four patients (16.0%); these included a wound infection, an
      intestinal obstruction, an afferent loop syndrome, and a reflux symptom. The
      average postoperative hospital stay of the patients was 12.5 days. There was no
      case of conversion to open surgery, anastomotic leakage or stenosis, or
      mortality. CONCLUSIONS: The overlap method for esophagojejunostomy or
      esophagogastrostomy after LTG or LPG is safe and feasible and does not require an
      additional minilaparotomy, which may result in less pain and favorable cosmetic
      outcomes.

PMID- 22398436
TI  - Diagnostic study and meta-analysis of C-reactive protein as a predictor of
      postoperative inflammatory complications after gastroesophageal cancer surgery.
AB  - PURPOSE: This study assessed the diagnostic accuracy of C-reactive protein (CRP)
      after gastroesophageal cancer resection for postoperative inflammatory
      complications (PIC). METHODS: The clinical data and CRP values of patients
      operated on for gastroesophageal cancer surgery between 1997 and 2009 were
      retrospectively analyzed. The results of this study were compared with published
      data using a meta-analytic approach for diagnostic outcomes. RESULTS: Of 210
      patients included in the study, 59 developed PIC (28.1 %; 95 % CI: 22.5-34.5 %).
      On the postoperative day (POD) 4 and 7, CRP had the best diagnostic accuracy for
      PIC (AUC 0.77; 95 % CI, 0.64-0.91, AUC 0.81; 95 % CI, 0.71-0.91). Using a cut-off
      value of 141 mg/L (95 % CI, 131-278 mg/L) for CRP on POD 4, the sensitivity was
      0.78 (95 % CI, 0.55-0.91), the specificity was 0.70 (95 % CI, 0.53-0.83) and the
      NPV was 0.89 (95 % CI, 0.77-0.95). The in-hospital mortality rate was 3.3 % (95 %
      CI, 1.5-6.9 %). In a diagnostic meta-analysis that included two additional
      studies, CRP had a significant predictive value after POD 3. CONCLUSION: There is
      limited evidence for the diagnostic accuracy of CRP levels for PIC after
      gastroesophageal cancer surgery. CRP levels on POD 4 might be useful to rule out
      PIC, but its diagnostic accuracy is moderate at best. For clinical routine use
      CRP levels are clearly not sufficient to predict PIC and have to be interpreted
      in the context of the whole clinical picture.

PMID- 22398437
TI  - Protective effect of Flos carthami extract against ethylene glycol-induced
      urolithiasis in rats.
AB  - Flos carthami (FC), also known as Carthamus tinctorius, is a traditional Chinese
      herbal plant that has been prescribed since centuries for treating various
      symptoms related to blood circulation improvement. This study aimed to
      investigate the effects of FC on calcium oxalate (CaOx) formation in ethylene
      glycol (EG)-fed rats. A total of 50 male Sprague-Dawley rats were divided into
      the following 6 groups: group 1, as the normal control (n = 5); group 2 received
      gastric gavages of starch and 0.75% EG (placebo, n = 5) as a stone inducer; group
      3 (n = 10) received EG and potassium citrate as positive controls; group 4 (n =
      10) received 0.75% EG and 300 mg/day FC; group 5 (n = 10) was treated with EG and
      600 mg/day FC; group 6 (n = 10) received with EG and 1,200 mg/day FC. For all
      experimental animals, 24-h urine and blood samples were analyzed at the beginning
      and end of the experiment. Kidney tissue was histopathologically examined using a
      polarized light microscope, and crystal deposits were evaluated by a semi
      quantitative scoring method; these scores were significantly lower in the FC
      groups (600 and 1,200 mg/day) than in the placebo group. Thus, FC administration
      appeared to inhibit the deposition of CaOx crystal EG-fed rats. We, therefore,
      consider that FC may be effective for preventing stone disease, albeit with
      certain side effects, such as a bleeding tendency. Further clinical trials are
      needed for evaluating its benefits and possible side effects.

PMID- 22398438
TI  - Construction of black (Rubus occidentalis) and red (R. idaeus) raspberry linkage
      maps and their comparison to the genomes of strawberry, apple, and peach.
AB  - The genus Rubus belongs to the Rosaceae and is comprised of 600-800 species
      distributed world-wide. To date, genetic maps of the genus consist largely of non
      transferable markers such as amplified fragment length polymorphisms. An F(1)
      population developed from a cross between an advanced breeding selection of Rubus
      occidentalis (96395S1) and R. idaeus 'Latham' was used to construct a new genetic
      map consisting of DNA sequence-based markers. The genetic linkage maps presented
      here are constructed of 131 markers on at least one of the two parental maps. The
      majority of the markers are orthologous, including 14 Rosaceae conserved
      orthologous set markers, and 60 new gene-based markers developed for raspberry.
      Thirty-four published raspberry simple sequence repeat markers were used to align
      the new maps to published raspberry maps. The 96395S1 genetic map consists of six
      linkage groups (LG) and covers 309 cM with an average of 10 cM between markers;
      the 'Latham' genetic map consists of seven LG and covers 561 cM with an average
      of 5 cM between markers. We used BLAST analysis to align the orthologous
      sequences used to design primer pairs for Rubus genetic mapping with the genome
      sequences of Fragaria vesca 'Hawaii 4', Malus * domestica 'Golden Delicious', and
      Prunus 'Lovell'. The alignment of the orthologous markers designed here suggests
      that the genomes of Rubus and Fragaria have a high degree of synteny and that
      synteny decreases with phylogenetic distance. Our results give unprecedented
      insights into the genome evolution of raspberry from the putative ancestral
      genome of the single ancestor common to Rosaceae.

PMID- 22398439
TI  - Reconstruction of the cervical spine with two osteocutaneous fibular flap after
      radiotherapy and resection of osteoclastoma : a case report.
AB  - Transfer of a vascularised free fibular bone for reconstruction of the cervical
      spine has been described previously.(1-4) However, this is the first report of a
      reconstruction with both an osteocutaneous fibular flap for anterior
      stabilisation and a double-islanded osteocutaneous fibular flap for posterior
      stability. We present a case of an osteoclastoma in C2 initially treated with
      radiotherapy 1.8 Gy * 30. Two months after radiotherapy, the patient developed
      severe osteoradionecrosis and luxation of C2 causing neurological impairment. The
      patient was treated with cervical traction for 10 days. Resection of C2 was
      performed through a posterior approach and a secondary transoral approach. The
      spine was stabilised from a posterior approach using allografts and a titanium
      plate and rod construct (Vertex) from the occipital squama to C5 and from an
      anterior approach with allograft filled cage from C1 to C3. Two months later,
      rupture of the pharyngeal wall was noted with exposure of the anterior cage. A
      few days later, the posterior scar ruptured. The anterior cage was removed and
      the pharyngeal wall was sutured. Revision of the posterior wound was performed,
      leaving the implants in place. To secure stability of the spine, the patient was
      treated with a HALO. Once again, the pharyngeal wall ruptured. Reconstruction of
      the posterior pharyngeal wall and the anterior column of the spine was performed
      with an osteocutaneous fibular flap from the skull base to C3. Five months later,
      a computed tomography (CT) scan showed insufficient bony fusion of both anterior
      and posterior bone grafts, and the posterior wound had not healed. A second
      osteocutaneous fibular flap was placed bilaterally from the occipital squama to
      the posterior elements of Th1, closing the wound defect. Apart from the occipital
      squama, fusion was seen at all sites after 14 months, and the HALO was removed.

PMID- 22398440
TI  - Inclusion controlled lanthanide-imidazolium functionalised carboxylate
      complexation.
AB  - Imidazolium functionalized carboxylic acid forms a multi-component material with
      p-sulfonatocalix[4]arene and aquated lanthanide ions, stabilising dinuclear metal
      complexes for Y(3+) and Gd(3+). These have the simplest binding of two bridging
      carboxylates between the two metal centres (Y(3+)), or the same arrangement along
      with the simplest binding of one carboxylate bridging two metal ions for the
      larger metal ion (Gd(3+)).

PMID- 22398441
TI  - Photocatalytic and photoelectric properties of cubic Ag3PO4 sub-microcrystals
      with sharp corners and edges.
AB  - Herein, we demonstrate a complex-precipitation strategy for high-yield
      fabrication of single-crystalline Ag(3)PO(4) sub-microcubes with sharp corners,
      edges, and smooth surfaces, which exhibit much higher photocatalytic activities
      and photoelectric conversion properties than spherical Ag(3)PO(4) particles and
      commercial N-doped TiO(2) under visible light irradiation.

PMID- 22398442
TI  - Phenotypic and molecular characterization of partial trisomy 2q resulting from
      insertion-duplication in chromosome 18q: a case report and review of literature.
AB  - Trisomy 2q is a well-documented chromosomal anomaly with considerable variation
      in the phenotype depending upon the breakpoints and the co-existing chromosomal
      aberrations. The case of a dysmorphic male infant found to have trisomy of the
      2q31.1-q37.3 segment, resulting from insertion-duplication of this segment in
      chromosome 18q23 is reported here. The rearrangement was resolved in detail by
      cytogenetic microarray and whole chromosome paint-based fluorescence in situ
      hybridization studies. There is some overlap of the phenotypic features in the
      reported patient with those described in previously reported cases with partial
      trisomy 2q. A detailed review of the available literature on 2q trisomy has also
      been presented and delineation of the phenotypic characteristics common to all
      patients with 2q trisomy has been attempted.

PMID- 22398443
TI  - A petunia ABC protein controls strigolactone-dependent symbiotic signalling and
      branching.
AB  - Strigolactones were originally identified as stimulators of the germination of
      root-parasitic weeds that pose a serious threat to resource-limited agriculture.
      They are mostly exuded from roots and function as signalling compounds in the
      initiation of arbuscular mycorrhizae, which are plant-fungus symbionts with a
      global effect on carbon and phosphate cycling. Recently, strigolactones were
      established to be phytohormones that regulate plant shoot architecture by
      inhibiting the outgrowth of axillary buds. Despite their importance, it is not
      known how strigolactones are transported. ATP-binding cassette (ABC)
      transporters, however, are known to have functions in phytohormone translocation.
      Here we show that the Petunia hybrida ABC transporter PDR1 has a key role in
      regulating the development of arbuscular mycorrhizae and axillary branches, by
      functioning as a cellular strigolactone exporter. P. hybrida pdr1 mutants are
      defective in strigolactone exudation from their roots, resulting in reduced
      symbiotic interactions. Above ground, pdr1 mutants have an enhanced branching
      phenotype, which is indicative of impaired strigolactone allocation.
      Overexpression of Petunia axillaris PDR1 in Arabidopsis thaliana results in
      increased tolerance to high concentrations of a synthetic strigolactone,
      consistent with increased export of strigolactones from the roots. PDR1 is the
      first known component in strigolactone transport, providing new opportunities for
      investigating and manipulating strigolactone-dependent processes.

PMID- 22398444
TI  - On the difficulty of increasing dental complexity.
AB  - One of the fascinating aspects of the history of life is the apparent increase in
      morphological complexity through time, a well known example being mammalian cheek
      tooth evolution. In contrast, experimental studies of development more readily
      show a decrease in complexity, again well exemplified by mammalian teeth, in
      which tooth crown features called cusps are frequently lost in mutant and
      transgenic mice. Here we report that mouse tooth complexity can be increased
      substantially by adjusting multiple signalling pathways simultaneously. We
      cultured teeth in vitro and adjusted ectodysplasin (EDA), activin A and sonic
      hedgehog (SHH) pathways, all of which are individually required for normal tooth
      development. We quantified tooth complexity using the number of cusps and a
      topographic measure of surface complexity. The results show that whereas
      activation of EDA and activin A signalling, and inhibition of SHH signalling,
      individually cause subtle to moderate increases in complexity, cusp number is
      doubled when all three pathways are adjusted in unison. Furthermore, the increase
      in cusp number does not result from an increase in tooth size, but from an
      altered primary patterning phase of development. The combination of a lack of
      complex mutants, the paucity of natural variants with complex phenotypes, and our
      results of greatly increased dental complexity using multiple pathways, suggests
      that an increase may be inherently different from a decrease in phenotypic
      complexity.

PMID- 22398446
TI  - The 2.8 A crystal structure of the dynein motor domain.
AB  - Dyneins are microtubule-based AAA(+) motor complexes that power ciliary beating,
      cell division, cell migration and intracellular transport. Here we report the
      most complete structure obtained so far, to our knowledge, of the 380-kDa motor
      domain of Dictyostelium discoideum cytoplasmic dynein at 2.8 A resolution; the
      data are reliable enough to discuss the structure and mechanism at the level of
      individual amino acid residues. Features that can be clearly visualized at this
      resolution include the coordination of ADP in each of four distinct nucleotide
      binding sites in the ring-shaped AAA(+) ATPase unit, a newly identified
      interaction interface between the ring and mechanical linker, and junctional
      structures between the ring and microtubule-binding stalk, all of which should be
      critical for the mechanism of dynein motility. We also identify a long-range
      allosteric communication pathway between the primary ATPase and the microtubule
      binding sites. Our work provides a framework for understanding the mechanism of
      dynein-based motility.

PMID- 22398447
TI  - The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier
      Gorlin syndrome.
AB  - The recognition of distinctly modified histones by specialized 'effector'
      proteins constitutes a key mechanism for transducing molecular events at
      chromatin to biological outcomes. Effector proteins influence DNA-templated
      processes, including transcription, DNA recombination and DNA repair; however, no
      effector functions have yet been identified within the mammalian machinery that
      regulate DNA replication. Here we show that ORC1--a component of ORC (origin of
      replication complex), which mediates pre-DNA replication licensing--contains a
      bromo adjacent homology (BAH) domain that specifically recognizes histone H4
      dimethylated at lysine 20 (H4K20me2). Recognition of H4K20me2 is a property
      common to BAH domains present within diverse metazoan ORC1 proteins. Structural
      studies reveal that the specificity of the BAH domain for H4K20me2 is mediated by
      a dynamic aromatic dimethyl-lysine-binding cage and multiple intermolecular
      contacts involving the bound peptide. H4K20me2 is enriched at replication
      origins, and abrogating ORC1 recognition of H4K20me2 in cells impairs ORC1
      occupancy at replication origins, ORC chromatin loading and cell-cycle
      progression. Mutation of the ORC1 BAH domain has been implicated in the aetiology
      of Meier-Gorlin syndrome (MGS), a form of primordial dwarfism, and ORC1 depletion
      in zebrafish results in an MGS-like phenotype. We find that wild-type human ORC1,
      but not ORC1-H4K20me2-binding mutants, rescues the growth retardation of orc1
      morphants. Moreover, zebrafish depleted of H4K20me2 have diminished body size,
      mirroring the phenotype of orc1 morphants. Together, our results identify the BAH
      domain as a novel methyl-lysine-binding module, thereby establishing the first
      direct link between histone methylation and the metazoan DNA replication
      machinery, and defining a pivotal aetiological role for the canonical H4K20me2
      mark, via ORC1, in primordial dwarfism.

PMID- 22398448
TI  - An oxygenase that forms and deoxygenates toxic epoxide.
AB  - Catabolism may give rise to toxic intermediates that compromise cell vitality,
      such as epoxide formation in the recently elucidated and apparently universal
      bacterial coenzyme A (CoA)-dependent degradation of phenylacetic acid. This
      compound is central to the catabolism of a variety of aromatics, such as
      phenylalanine, lignin-related compounds or environmental contaminants. The key
      phenylacetyl-CoA monooxygenase (epoxidase) of the pathway, PaaABCE, is also
      connected to the production of various primary and secondary metabolites, as well
      as to the virulence of certain pathogens. However, the enzyme complex has so far
      not been investigated in detail. Here we characterize the bacterial
      multicomponent monooxygenase PaaABCE that, surprisingly, not only transforms
      phenylacetyl-CoA into its ring-1,2-epoxide, but also mediates the NADPH-dependent
      removal of the epoxide oxygen, regenerating phenylacetyl-CoA with formation of
      water. We provide evidence for a catalytic di-iron centre that is probably the
      key to the unprecedented deoxygenation of an organic compound by an oxygenase.
      Presumably, the bifunctionality is vital to avoid toxic intracellular epoxide
      levels if the subsequent catabolic steps are impeded. Our data suggest that
      detoxification is assisted by two thioesterases (PaaI and PaaY) forming non
      reactive breakdown products. Hence, PaaABCE may harbour an intrinsic escape
      mechanism from its own toxic product and represents the archetype of a
      bifunctional oxygenase/deoxygenase. Analogous reactions may possibly be catalysed
      by other di-iron epoxidases.

PMID- 22398449
TI  - Neurodegeneration: Trouble in the cell's powerhouse.

PMID- 22398450
TI  - Phase transitions in the assembly of multivalent signalling proteins.
AB  - Cells are organized on length scales ranging from angstrom to micrometres.
      However, the mechanisms by which angstrom-scale molecular properties are
      translated to micrometre-scale macroscopic properties are not well understood.
      Here we show that interactions between diverse synthetic, multivalent
      macromolecules (including multi-domain proteins and RNA) produce sharp liquid
      liquid-demixing phase separations, generating micrometre-sized liquid droplets in
      aqueous solution. This macroscopic transition corresponds to a molecular
      transition between small complexes and large, dynamic supramolecular polymers.
      The concentrations needed for phase transition are directly related to the
      valency of the interacting species. In the case of the actin-regulatory protein
      called neural Wiskott-Aldrich syndrome protein (N-WASP) interacting with its
      established biological partners NCK and phosphorylated nephrin, the phase
      transition corresponds to a sharp increase in activity towards an actin
      nucleation factor, the Arp2/3 complex. The transition is governed by the degree
      of phosphorylation of nephrin, explaining how this property of the system can be
      controlled to regulatory effect by kinases. The widespread occurrence of
      multivalent systems suggests that phase transitions may be used to spatially
      organize and biochemically regulate information throughout biology.

PMID- 22398452
TI  - Stapling and cutting a thermometer during sleeve gastrectomy: a preventable
      complication.

PMID- 22398451
TI  - Resonant quantum transitions in trapped antihydrogen atoms.
AB  - The hydrogen atom is one of the most important and influential model systems in
      modern physics. Attempts to understand its spectrum are inextricably linked to
      the early history and development of quantum mechanics. The hydrogen atom's
      stature lies in its simplicity and in the accuracy with which its spectrum can be
      measured and compared to theory. Today its spectrum remains a valuable tool for
      determining the values of fundamental constants and for challenging the limits of
      modern physics, including the validity of quantum electrodynamics and--by
      comparison with measurements on its antimatter counterpart, antihydrogen--the
      validity of CPT (charge conjugation, parity and time reversal) symmetry. Here we
      report spectroscopy of a pure antimatter atom, demonstrating resonant quantum
      transitions in antihydrogen. We have manipulated the internal spin state of
      antihydrogen atoms so as to induce magnetic resonance transitions between
      hyperfine levels of the positronic ground state. We used resonant microwave
      radiation to flip the spin of the positron in antihydrogen atoms that were
      magnetically trapped in the ALPHA apparatus. The spin flip causes trapped anti
      atoms to be ejected from the trap. We look for evidence of resonant interaction
      by comparing the survival rate of trapped atoms irradiated with microwaves on
      resonance to that of atoms subjected to microwaves that are off-resonance. In one
      variant of the experiment, we detect 23 atoms that survive in 110 trapping
      attempts with microwaves off-resonance (0.21 per attempt), and only two atoms
      that survive in 103 attempts with microwaves on-resonance (0.02 per attempt). We
      also describe the direct detection of the annihilation of antihydrogen atoms
      ejected by the microwaves.

PMID- 22398453
TI  - Baseline serum tryptase levels and adverse reactions to injection specific
      immunotherapy with airborne allergens: is there a relationship?
AB  - BACKGROUND: Elevated baseline serum tryptase levels are associated with severe
      systemic reactions following hymenoptera stings or venom immunotherapy. Little is
      known about baseline tryptase levels in patients with respiratory allergy and
      whether a relationship exists with systemic reactions induced by injection
      specific immunotherapy (SIT) with airborne allergens. The objective of this study
      was to measure tryptase levels in subjects with respiratory allergy and analyze
      the results in the light of tolerance/intolerance to injection SIT. METHODS:
      Baseline serum tryptase levels were measured in 106 adults allergic to different
      airborne allergens and in 40 normal controls. Thirty-one patients underwent
      injection SIT, and 15 of these 31 experienced at least one SIT-induced systemic
      reaction. RESULTS: Patients and normal controls showed similar median tryptase
      levels (2.98 vs. 3.13 ng/ml, respectively), although these were elevated in 6
      patients (6%) versus 0 of 40 controls (0%). Tryptase levels did not differ
      between those patients with or without a history of systemic reactions (median
      3.7 vs. 5.91 ng/ml, not significant). Three of 4 patients showing elevated
      tryptase levels belonged to the SIT-tolerant group. Elevated tryptase levels were
      not associated with specific allergens nor with distance from the specific pollen
      season. A bone marrow aspirate performed in the only patient with a history of
      systemic reactions following injection SIT and tryptase >11.4 ng/ml showed a
      normal morphology and phenotype. CONCLUSIONS: Unlike patients with hymenoptera
      venom allergy, in patients with respiratory allergy, elevated serum tryptase
      levels do not represent a risk factor for adverse reactions to SIT.

PMID- 22398454
TI  - Fabrication of non-planar silver nano-arc-gap arrays.
AB  - We developed a method to fabricate an array of silver non-planar nano-arc-gaps
      via inverted hemispherical colloidal lithography and shadow metal evaporation
      methods. It is found that there is a localized surface plasmon mode which results
      in extraordinary optical transmission. The electric field is strongly localized
      at the nano-arc-gap region and therefore induces a resonance that has an ultra
      small mode volume of less than 2.44 * 10(-6) MUm(3). The ratio of the quality
      factor to the mode volume is as high as 1.44 * 10(6) MUm(-3). This would be
      valuable for the design of optoelectric circuits.

PMID- 22398455
TI  - Comparative evaluation of Diaton and Goldmann applanation tonometers.
AB  - AIM: To evaluate the agreement between intra-ocular pressure (IOP) measurements
      with the Diaton and the Goldmann applanation tonometers (GAT). METHODS: In this
      cross-sectional observational study, a total of 196 eyes of 196 participants (66
      patients with glaucoma, 130 healthy subjects) were included. IOP measurements
      were obtained from all patients using the Diaton and GAT. RESULTS: The average
      age of the patients enrolled in this study was 48.3 +/- 14.6 years (range 18-79).
      The overall mean IOP measured by the Diaton was 17.2 +/- 6.4 mm Hg, while that in
      glaucoma patients was 17.9 +/- 6.2 mm Hg and in the control group 15.8 +/- 4.9 mm
      Hg. Pearson's correlation coefficient showed a moderate correlation in IOP
      measurements by the two instruments in healthy controls (r = 0.460, p < 0.01);
      however, the same correlation for the glaucomatous subjects was noted to be poor
      (r = 0.261, p = 0.57). The limits of agreement (95% confidence intervals) ranged
      from -9.9 to +11.2 and from -15.3 to +19.7 mm Hg in healthy controls and glaucoma
      patients, respectively. CONCLUSION: The Diaton measurements do not correlate well
      with those provided by applanation tonometry. The two tonometers show very wide
      limits of agreement so they may not be used interchangeably in clinical practice
      for the measurement of IOP.

PMID- 22398457
TI  - Colonization of the oral cavity by probiotic bacteria.
AB  - The aim of this study was to investigate if three probiotic bacteria present in
      the milk product Cultura Dofilus(r) naturell could be detected in saliva and on
      oral mucosal surfaces, and if they colonized dental surfaces in situ in 8 caries
      inactive individuals after 8 daily exposures to the milk product for up to 3
      days. Bacteria were identified by fluorescence in situ hybridization and confocal
      laser scanning microscopy. While probiotic bacteria were present sporadically in
      the oral cavity on mucosal surfaces and in saliva after 3 days of frequent use of
      the probiotic milk, they were not detected on dental surfaces. Probiotic bacteria
      may thus contribute to general oral health, but their potential role in biofilm
      induced dental diseases remains unclear.

PMID- 22398458
TI  - The effect of fibrin glue on the early healing phase of intestinal anastomoses in
      the rat.
AB  - PURPOSE: Protecting the anastomotic integrity using suture or staple line
      reinforcement remains an important goal for ongoing research. The present
      comprehensive study aims to establish the effects of fibrin glue on the early
      phase of anastomotic healing in the rat intestine. METHODS: One hundred and eight
      young adult male Wistar rats underwent resection and anastomosis of both the
      ileum and colon. In half, fibrin glue was applied around the anastomoses.
      Parameters for repair included wound strength, both bursting pressure and
      breaking strength at days 1, 3, and 5 after operation; hydroxyproline content;
      and histology, the latter also after 7 days. RESULTS: A transient colonic ileus
      was observed in the experimental group. Anastomotic breaking strength was always
      similar in both the control and fibrin glue groups. Anastomotic bursting
      pressures remained low at days 1 and 3, without any differences between the
      groups. In both groups, the bursting pressure increased sharply (p < 0.001)
      between days 3 and 5. At day 5, the bursting pressure in the fibrin glue group
      remained below than that in the controls, although only significantly (p =
      0.0138) so in the ileum. At day 5, but not at day 7, the wounds in the fibrin
      glue group contained less collagen. Other aspects of microscopic wound
      architecture appeared to be the same. CONCLUSIONS: There is no justification for
      using fibrin glue on patent anastomoses constructed under low-risk conditions.
      Its potential benefit under conditions where chances for anastomotic leakage are
      enhanced needs further investigation.

PMID- 22398459
TI  - Electrolyte-free water clearance versus modified electrolyte-free water
      clearance: do the results justify the effort?
AB  - BACKGROUND: Calculation of electrolyte-free water clearance (EFWC) allows for
      quantification of renal losses of free water and was shown to be helpful in the
      differential diagnosis of dysnatremias and might help in the correction of the
      electrolyte disorders. A modified EFWC formula (MEFWC) was described to be more
      accurate than the conventional one; however, it has never been evaluated
      clinically. METHODS: In order to evaluate the performance of MEFWC compared to
      EFWC under clinical circumstances, we gathered data from a total of 912 patient
      days of 138 critically ill patients. EFWC and MEFWC were calculated on the basis
      of these data. Additionally, from data of critically ill patients, we calculated
      a prediction of serum sodium based on the Edelman equation using either EFWC or
      MEFWC and compared results. RESULTS: Altogether, 343 normonatremic, 124
      hyponatremic and 445 hypernatremic days were analyzed. Results for EFWC and MEFWC
      correlated significantly (R = 0.98). In patients with hyponatremia, the absolute
      difference between EFWC and MEFWC was significantly larger than in patients with
      normonatremia (437 vs. 256 ml, p < 0.01). The absolute difference between EFWC
      and MEFWC correlated significantly with the level of serum sodium (R = -0.41).
      The mean difference in the prediction of serum sodium change as calculated based
      on the Edelman equation between the formula using EFWC and the formula using
      MEFWC was 0.7 mmol/l (SD 0.68) and was highest in hyponatremia and lowest in
      hypernatremia. CONCLUSION: Results of EFWC and MEFWC were comparable in
      critically ill patients. Under normal circumstances, the use of the more
      complicated MEFWC is not justified. In hyponatremia, the difference between EFWC
      and MEFWC is larger and thus might justify the use of the more complicated
      formula.

PMID- 22398460
TI  - Risk factors for feline infectious peritonitis in Australian cats.
AB  - The objective of this study was to determine whether patient signalment (age,
      breed, sex and neuter status) is associated with naturally-occurring feline
      infectious peritonitis (FIP) in cats in Australia. A retrospective comparison of
      the signalment between cats with confirmed FIP and the general cat population was
      designed. The patient signalment of 382 FIP confirmed cases were compared with
      the Companion Animal Register of NSW and the general cat population of Sydney.
      Younger cats were significantly over-represented among FIP cases. Domestic
      crossbred, Persian and Himalayan cats were significantly under-represented in the
      FIP cohort, while several breeds were over-represented, including British
      Shorthair, Devon Rex and Abyssinian. A significantly higher proportion of male
      cats had FIP compared with female cats. This study provides further evidence that
      FIP is a disease primarily of young cats and that significant breed and sex
      predilections exist in Australia. This opens further avenues to investigate the
      role of genetic factors in FIP.

PMID- 22398461
TI  - Recurrent pulmonary edema secondary to elongated soft palate in a cat.
AB  - A 9-month-old intact female Persian cat presented with recurrent pulmonary edema
      secondary to an elongated soft palate. Endoscopic evaluation of the pharynx and
      larynx showed that the elongated soft palate was overlying the epiglottis.
      Partial resection of the soft palate was performed and the cat showed no further
      respiratory signs. This report is the first description of elongated soft palate
      causing airway obstruction in a brachycephalic cat.

PMID- 22398462
TI  - Bilateral fusion of a supernumerary kidney in a cat.
AB  - A rare case of bilateral fusion of a supernumerary kidney was found during the
      necropsy of a female, 8-year-old, mixed breed cat that died as a result of
      azotemia and chronic enteritis. Apart from enteritis, necropsy revealed four
      kidneys, two in the sublumbar left region and two in the sublumbar right region,
      with cortical and medullary regions well individualized and independent; however,
      the pelvis was partially fused, giving rise to a single ureter. The kidneys were
      small, whitish and firm, with irregular surfaces. Microscopically, all kidneys
      displayed normal renal glomeruli and tubules among the immature renal glomeruli
      and tubules with characteristics of hypoplasia. Foci of glomerulosclerosis,
      nephrocalcinosis and interstitial fibrosis were also observed.

PMID- 22398464
TI  - Conventional aortic valve replacement: still a feasible option in the
      transcatheter aortic valve implantations era?

PMID- 22398463
TI  - Do tumours located in the left lower lobe have worse outcomes in lymph node
      positive non-small cell lung cancer than tumours in other lobes?
AB  - OBJECTIVES: Although an association between prognosis and lobar location of lung
      cancer, particularly the left lower lobe (LLL), has been suggested, the certainty
      of such association remains controversial. The purpose of this study was to
      evaluate the impact of tumour lobar location on surgical outcomes as an
      independent prognostic factor for survival in our non-small cell lung cancer
      (NSCLC) patient series. METHODS: We retrospectively reviewed 978 NSCLC patients
      who underwent complete resection in our hospital between 2000 and 2007. We
      statistically analysed the association between clinicopathological factors and
      clinical outcomes. RESULTS: Among the 978 patients reviewed, the NSCLC was
      located in the LLL in 143 (14.6%) patients, and lymph node involvement was
      identified in 210 patients (21.5%). The 5-year overall survival rates of patients
      whose NSCLC was located in the LLL and in other lobes (non-LLL) were 73.1 and
      74.3%, respectively, and showed no significant association (P = 0.86). On the
      other hand, the 5-year survival rates of patients whose NSCLC occurred in the LLL
      (n = 33) and non-LLL (n = 177) and with lymph node metastasis were 32.7 and
      57.7%, respectively, and showed a significant association (P = 0.01). Therefore,
      we performed a more detailed analysis on the 210 NSCLC patients with lymph node
      metastasis. On multivariate analysis, we found that LLL tumour (P = 0.02), tumour
      size >3 cm (P = 0.02) and N status (P < 0.001) were significant independent
      predictors for survival. CONCLUSIONS: LLL tumours with lymph node metastasis are
      strongly associated with mortality in NSCLC patients. The location of the primary
      tumour may contribute in determining the optimal management strategy and accurate
      prediction of prognosis.

PMID- 22398465
TI  - Studies of isolated global brain ischaemia: I. Overview of irreversible brain
      injury and evolution of a new concept - redefining the time of brain death.
AB  - Despite advanced cardiac life support (ACLS), the mortality from sudden death
      after cardiac arrest is 85-95%, and becomes nearly 100% if ischaemia is
      prolonged, as occurs following unwitnessed arrest. Moreover, 33-50% of survivors
      following ACLS after witnessed arrest develop significant neurological
      dysfunction, and this rises to nearly 100% in the rare survivors of unwitnessed
      arrest. Although, whole body (cardiac) survival improves to 30% following recent
      use of emergency cardiopulmonary bypass, sustained neurological dysfunction
      remains a devastating and unresolved problem. Our studies suggest that both brain
      and whole body damage reflect an ischaemic/reperfusion injury that follows the
      present reperfusion methods that use normal blood, which we term 'uncontrolled
      reperfusion'. In contrast, we have previously introduced the term 'controlled
      reperfusion', which denotes controlling both the conditions (pressure, flow and
      temperature) as well as the composition (solution) of the reperfusate. Following
      prolonged ischaemia of the heart, lung and lower extremity, controlled
      reperfusion resulted in tissue recovery after ischaemic intervals previously
      thought to produce irreversible cellular injury. These observations underlie the
      current hypothesis that controlled reperfusion will become an effective treatment
      of the otherwise lethal injury of prolonged brain ischaemia, such as with
      unwitnessed arrest, and we tested this after 30 min of normothermic global brain
      ischaemia. This review, and the subsequent three studies will describe the
      evolution of the concept that controlled reperfusion will restore neurological
      function to the brain following prolonged (30 min) ischaemia. To provide a
      familiarity and rationale for these studies, this overview reviews the background
      and current treatment of sudden death, the concepts of controlled reperfusion,
      recent studies in the brain during whole body ischaemia, and then summarizes the
      three papers in this series on a new brain ischaemia model that endorses our
      hypothesis that controlled reperfusion allows complete neurological recovery
      following 30 min of normothermic global brain ischaemia. These findings may
      introduce innovative management approaches for sudden death, and perhaps stroke,
      because the brain is completely salvageable following ischaemic times thought
      previously to produce infarction.

PMID- 22398466
TI  - Aortic arch pseudoaneurysm caused by a fish bone.

PMID- 22398467
TI  - Completion pneumonectomy: a multicentre international study on 165 patients.
AB  - OBJECTIVES: We evaluated factors that influenced morbidity and mortality in
      patients undergoing completion pneumonectomy (CP). METHODS: A retrospective
      review of a consecutive series of patients who underwent CP at six international
      centres. RESULTS: In total, 165 CP were performed between March 1990 and December
      2009: 152 for malignant disease and 13 for benign disease. Forty-two patients
      (25.4%) underwent neoadjuvant therapy. Right CP was performed in 99 patients
      (60%) and left in 66 (40%). Thoracotomy was employed in 161 patients and median
      sternotomy in 4. Stapled closure of the bronchus was performed in 121 patients
      and hand closure in 44. The overall operative mortality was 10.3% (17 of 165).
      Operative mortality was 10.5% (16 of 152) in malignant diseases and 7.7% (1 of
      13) in benign diseases. Complications occurred in 55.1% (91 of 165) of patients.
      Mean hospital stay was 16.02 +/- 16.8 days (range: 3-151 days). Thirteen patients
      (7.9%) developed bronchopleural fistulas. No statistically significant
      relationship was found in mortality or morbidity according to side, gender,
      induction therapy and surgical approach. Stapled compared with hand closure for
      the bronchus did not affect the bronchopleural fistula rate (P = 0.4). The
      overall 5-year survival was 37.6%: 70.1% in benign disease (13 patients), 48.9%
      in squamous cell carcinoma of the lung (63 patients), 23.9% in primary lung
      adenocarcinoma (62 patients), 50% in grade 1 and grade 2 neuroendocrine carcinoma
      of the lung (4 patients), 54.7% in metastatic disease (14 patients) and 0% in
      primary lung sarcomas. A statistically significant better survival was observed
      in patients with squamous cell carcinoma versus adenocarcinoma (P = 0.04).
      CONCLUSIONS: CP shows an acceptable operative mortality with a high morbidity
      rate. The overall 5-year survival is acceptable in properly selected patients
      (i.e. squamous cell carcinoma, metastatic disease). Side, gender, induction
      therapy and surgical approach did not influence mortality and morbidity.

PMID- 22398469
TI  - Leonardo Da Vinci Award for training excellence.

PMID- 22398468
TI  - Impact of the severity of acute rejection in the early phase after rat lung
      transplantation on the effectiveness of mycophenolate mofetil to treat chronic
      allograft rejection.
AB  - OBJECTIVES: Prevention and treatment of bronchiolitis obliterans (BO) after lung
      transplantation (LTX) remains disappointing. The high prevalence and the critical
      detection of early mild acute lung rejection aggravated optimum immunosuppressive
      therapy. In this study, two hypotheses were investigated: (i) mycophenolate
      mofetil (MMF) prevented the development of BO after rat LTX. (ii) The
      effectiveness of MMF depended on the degree of acute rejection (AR) at the time
      of drug initiation. METHODS: A rat model of left lung allo-transplantation
      (Fisher 344 to Wistar Kyoto) was used to evaluate the basic effect of MMF (30
      mg/kg body weight per day) on the development BO. MMF therapy began on Days 0, 7
      and 14 after transplantation characterizing different degree of AR of the
      allograft at the time of drug initiation and ended on Day 60 after
      transplantation. Non-treated animals were used as controls. Histopathological
      alterations were analysed according to the International Society for Heart and
      Lung Transplantation (ISHLT). RESULTS: MMF treatment of allografts with high
      grade AR (ISHLT-A3-4/B2R; from Day 14 to 60) failed. All animals developed
      vascular fibrosis and BO. Promising long-term outcome was shown after treatment
      of mild to moderate acute rejecting of allografts (MMF from Day 7 to 60). The
      proportion of animals with high grade acute airway inflammation was significantly
      reduced (33%; P<0.05). All animals were free of BO and chronic vascular
      alterations (90%). MMF (Day 0-60) significantly reduced the proportion of animals
      with severe acute vascular rejection and high grade airway inflammation (17 and
      0%, respectively; P<0.05, each). None of the animals treated with MMF from Day 0
      to 60 developed chronic rejection (CR). CONCLUSIONS: MMF significantly reduced AR
      and CR after rat LTX. However, only allografts with no or mild AR at the time of
      drug initiation benefited from MMF treatment. In addition, the appearance of
      early signs of fibroproliferative alterations in the airway structures might
      prevent a successful long-term outcome.

PMID- 22398470
TI  - A useful technique for specimen extraction from the thorax: the vacuum-packing
      method.
AB  - Most thoracic surgeons have encountered a number of situations in which a
      specimen was too large to fit through a small intercostal incision. This report
      highlights a useful technique for specimen extraction from the thorax using a
      vinyl bag and a sucker. The sucker creates negative pressure, and the liquid and
      air components from the specimen are removed. The specimen can be deflated and
      removed from the thoracic cavity through the access incision. We call this method
      the 'vacuum-packing method'.

PMID- 22398471
TI  - Low stroke rate and few thrombo-embolic events after HeartMate II implantation
      under mild anticoagulation.
AB  - OBJECTIVES: Bleeding and thrombo-embolism are two of the most threatening adverse
      events associated with the use of continuous flow left ventricular assist devices
      (LVADs) in the treatment of severe heart failure. We analysed our LVAD patients
      treated with the HeartMate II (HM II) device by following a low anticoagulation
      regimen. METHODS: Between 2008 and February 2011, we implanted 40 HM II LVADs in
      our institution. Intention to treat was bridge to transplant in 25, destination
      therapy in 9, bridge to candidacy in 5 cases and bridge to recovery in 1 case.
      Heparin was started only after 24 h postoperatively, and Phenprocumon (Phen) was
      started after removal of all chest drains. International normalized ratio (INR)
      target in the years 2008-2009 was 2.5, and 2.0-2.5 since 2010. Acetyl salicylic
      acid (ASA) was prescribed 50-100 mg/day only in patients <55 years or in case of
      severe atherosclerotic disease of the right coronary artery. All data were
      analysed consecutively concerning thrombo-embolic and bleeding events. RESULTS:
      Fifty-two percent of the patients were in INTERMACS level 1 or 2 at the time of
      implantation. The mean age was 58 +/- 11 years, and the mean days under LVAD was
      241 days (maximum: 1052 days). The survival rate was 87.5% after 30 years and 75%
      in the long term. Early postoperatively, no strokes or thrombo-embolic events
      occurred. In the long term, two patients suffered from ischaemic strokes, but
      recovered well. In both of these index events, the INR was lasting below 1.4. One
      of these two patients developed pump thrombosis additionally. Only three patients
      (ASA + Phen) developed gastrointestinal bleeding (7.5%). Two patients were
      withdrawn from Phen + ASA because of multiple angiodysplasia. CONCLUSIONS:
      Compared with the literature, even a mild anticoagulation protocol does not
      increase the risk of thrombotic events, but reduces bleeding events in the use of
      an HM II LVAD.

PMID- 22398472
TI  - Message from the Office of Nursing Policy.

PMID- 22398473
TI  - The Research to Action Project: Applied Workplace Solutions for Nurses.
AB  - The number of new nurses entering the profession has increased, but the need to
      retain nurses in the profession continues to be a critical priority. The
      consequences of the nursing shortage are reflected in continued high levels of
      overtime, absenteeism and turnover. The Canadian Federation of Nurses Unions
      (CFNU), in partnership with the Canadian Nurses Association, the Canadian
      Healthcare Association and the Dietitians of Canada, initiated the project
      Research to Action: Applied Workplace Solutions for Nurses (RTA). The RTA
      initiative comprised research-based pilot projects, implemented in 10
      jurisdictions across the country, that aimed to improve workplaces and increase
      the retention and recruitment of nurses. Unions, employers, governments,
      universities and professional associations came together in an unprecedented show
      of collaboration. Lessons and knowledge were shared among the projects, which
      were evaluated for their viability in other jurisdictions and professions. The
      pilots led to increased leadership, engagement and professional development, and
      decreased overtime, absenteeism and turnover.

PMID- 22398474
TI  - Research to Action: an evaluation.
AB  - The evaluation of the Research to Action project was conducted using an Outcome
      Mapping (OM) methodology (Earl et al. 2001) with a mixed-methods, repeat survey
      (before/after) study design. This design uses concurrent measurement of process
      and outcome indicators at baseline and follow-up. The RTA project proved
      effective at improving work environments and thereby promoting the retention and
      recruitment of nurses. Nurses involved in the RTA initiatives had a higher
      perception of leadership and support in their units, improved job satisfaction,
      increased empowerment and occupational commitment, and a greater intention to
      stay on the job.The pilot projects were most successful when there were clearly
      stated objectives, buy-in from nurses, support from the steering committee and
      management, and adequate communication among stakeholders. Committed coordination
      and leadership, both locally and nationally, were central to success.Considerable
      evidence has documented the challenges facing Canada's nursing human resources
      and their workplaces, such as high levels of turnover, excessive use of overtime
      and persistent shortages. There is a growing imperative to translate this
      research into action, and much of the available evidence presents viable policy
      alternatives for consideration. For example, a recent national synthesis report
      (Maddalena and Crupi 2008) recommended that, in consultation with stakeholders,
      processes should be put in place to share knowledge and best practices in nursing
      management, practice, staffing models and innovations in workplace health and
      well-being.Nurses across the country report a desire to be more involved in
      decisions affecting them and their patients (Wortsman and Janowitz 2006). A
      recent study on the shortage of registered nurses in Canada (Tomblin Murphy et
      al. 2009) highlighted the need for collaboration among governments, employers,
      unions and other stakeholders to improve working conditions for nurses. Another
      report notes the potential benefits of reduced turnover among nurses, the cost of
      which has been identified as a major burden on the Canadian healthcare system
      (O'Brien-Pallas et al. 2010). One of the goals of the pan-Canadian framework for
      health human resources (HHR) planning adopted by the
      Federal/Provincial/Territorial Advisory Committee on Health Delivery and Human
      Resources is to enhance all jurisdictions' capacity to build and maintain a
      sustainable workforce in healthy, safe work environments (ACHDHR 2005).Within
      this context, Health Canada's Office of Nursing Policy provided funding to the
      Canadian Federation of Nurses Unions (CFNU) and partner agencies in October 2008
      to develop pilot projects across the country aimed at improving nurse retention
      and recruitment through various workplace improvement schemes. Each of the
      provincial partners contributed funds, in-kind support or both to the projects.
      The initiative was entitled Research to Action: Applied Workplace Solutions for
      Nurses (RTA). A national steering committee including representation from unions,
      governments and employers, each pilot project, CFNU and its national partners -
      the Canadian Nurses Association, the Canadian Healthcare Association and the
      Dietitians of Canada - was formed to oversee the development of 10 pilot
      projects. There was one project in each of Newfoundland and Labrador, Nova
      Scotia, New Brunswick, Prince Edward Island, Ontario, Manitoba, Saskatchewan,
      Alberta, British Columbia and Nunavut. The pilot projects, led by their own
      steering committees, focused on various aspects of nursing practice identified as
      particularly relevant to each jurisdiction, with a specific emphasis on improving
      the work life of nurses and transforming research knowledge into practice. The
      goals of the RTA initiative were to promote high-quality workplace environments,
      improve the retention and recruitment of nurses (RNs and LPNs), enhance the
      quality of patient care and engage stakeholders in collaborative partnerships.
      The first project began in May 2009 and the last project was completed in March
      2011.

PMID- 22398475
TI  - 80/20 projects: introduction.
AB  - Nurses work a disproportionate amount of paid and unpaid overtime, are threatened
      by assault and injury, are overworked and have high rates of illness and injury
      (see, for example, Lasota 2009; Shields and Wilkins 2006; O'Brien-Pallas et al.
      2004; Aiken et al. 2002). These factors hamper retention and recruitment efforts,
      adding to Canada's growing nursing shortage, which could reach as high as 60,000
      full-time equivalents by 2022 (Tomblin Murphy et al. 2009). The lack of available
      nurses and the poor working conditions are mutually reinforcing. What is more,
      these conditions impede nurses from providing patient-centred care (Curtin 2003;
      Aiken et al. 2002; Baumann et al. 2001).

PMID- 22398476
TI  - British Columbia: improving retention and recruitment in smaller communities.
AB  - This pilot project involved the application, in Canada, of the innovative 80/20
      staffing model to a hospital in a small rural setting. The model provides the
      voluntary participants with 20% of their salaried time off from direct patient
      care in order to pursue various types of professional development activities. The
      project, overseen by a steering committee, lasted from June 2009 to February 2010
      and involved 14 nurses on the pediatric unit of Royal Inland Hospital in
      Kamloops, British Columbia. It entailed a collaborative partnership of the
      British Columbia Nurses' Union, Interior Health Authority, Thompson Rivers
      University and the British Columbia Ministry of Health, and aimed to demonstrate
      how professional development opportunities can improve recruitment and retention
      of nurses, quality of work life and quality of patient care.

PMID- 22398477
TI  - Newfoundland and Labrador: 80/20 staffing model pilot in a long-term care
      facility.
AB  - This project, based in Newfoundland and Labrador's Central Regional Health
      Authority, is the first application of an 80/20 staffing model to a long-term
      care facility in Canada. The model allows nurse participants to spend 20% of
      their paid time pursuing a professional development activity instead of providing
      direct patient care. Newfoundland and Labrador has the highest aging demographic
      in Canada owing, in part, to the out-migration of younger adults. Recruiting and
      retaining nurses to work in long-term care in the province is difficult; at the
      same time, the increasing acuity of long-term care residents and their complex
      care needs mean that nurses must assume greater leadership roles in these
      facilities. This project set out to increase capacity for registered nurse (RN)
      leadership, training and support and to enhance the profile of long-term care as
      a place to work. Six RNs and one licensed practical nurse (LPN) participated and
      engaged in a range of professional development activities. Several of the
      participants are now pursuing further nursing educational activities. Central
      Health plans to continue a 90/10 model for one RN and one LPN per semester, with
      the timeframe to be determined. The model will be evaluated and, if it is deemed
      successful, the feasibility of implementing it in other sites throughout the
      region will be explored.

PMID- 22398478
TI  - Nova Scotia: late career nurse and new graduate transition.
AB  - Addressing Canada's growing shortage of nurses requires effective strategies for
      their education, retention and recruitment. Although Nova Scotia produces more
      than 250 registered nurses and 125 licensed practical nurses each year, some 20%
      of these graduates leave the province to work elsewhere. The Nova Scotia Research
      to Action project focused on three retention and recruitment projects: (a) a new
      nurse graduate orientation/transition framework, (b) guidelines for nursing
      mentorship and (c) an online employment tool to assist in the hiring of new nurse
      graduates. Project partners continue to work collaboratively to advance these
      provincial initiatives.

PMID- 22398479
TI  - Mentorship projects: introduction.

PMID- 22398480
TI  - Manitoba: enhanced orientation for nurses new to long-term care.
AB  - The Manitoba pilot project, Enhanced Orientation for Nurses New to Long-Term
      Care, lasted 18 months and involved three sites in the Winnipeg Regional Health
      Authority. It was developed to address the reality that individuals entering long
      term care have more complex needs than in the past and that it is often difficult
      to recruit and retain nurses to work in this care setting. This mentorship
      program included 11 mentors and 12 proteges. As well, six clinical workshops were
      developed and held for a total of 390 participants. Proteges reported a positive
      effect on their transition to the workplace and their confidence levels, and
      mentors reported building their mentorship skills. The program has been expanded
      within the Winnipeg Region and to other health regions in the province and in
      Canada.

PMID- 22398481
TI  - New Brunswick: development of a Web-based orientation program and enhancing
      senior nurses' mentoring skills.
AB  - This project to help new nurse recruits integrate into the hospital work
      environment had two components: the development of a new web-based orientation
      tool in French for new recruits and mentor training for more experienced nurses.
      The aim of the first component was to redesign delivery of the nursing
      orientation program by assessing individual needs of new recruits and developing
      "just in time" information sessions with online access and e-learning modules.
      The second component aimed to develop a voluntary mentorship training program for
      senior nurses that offered training on the role and responsibility of mentors. A
      total of 30 orientation modules were created as resources that could be adapted
      to the needs of each nursing unit and accessed online. Sixty nurse recruits used
      the programs. A mentor training program was developed, and 28 nurses were trained
      as mentors. The mentorship literature and guides, produced in French, will be a
      valuable resource for francophone nurses across Canada.

PMID- 22398482
TI  - Skills upgrading projects: introduction.

PMID- 22398483
TI  - Prince Edward Island: building capacity--the implementation of a critical
      care/emergency program.
AB  - Like other Canadian provinces, Prince Edward Island has a shortage of experienced
      nurses, especially in critical and emergency care. To increase the numbers of
      competent nurses, a PEI-based nursing course in these areas was identified as key
      to building capacity. This Research to Action pilot program successfully involved
      nurses in PEI-based emergency and critical care courses developed by the Nova
      Scotia Registered Nurses Professional Development Centre and funded by Human
      Resources and Skills Development Canada. The programs were offered on a full-time
      basis, lasted 14 weeks and included classroom and simulation laboratory time,
      along with a strong clinical component.Sixteen RNs graduated from the courses and
      became Advanced Cardiovascular Life Support (ACLS) certified. An additional 12
      RNs were trained as preceptors. Feedback from participants indicates greater job
      satisfaction and increased confidence in providing patient assessments and care.
      Based on the program's success, the RTA partners proposed the establishment of an
      ongoing, PEI-based critical care and emergency nursing program utilizing 80/20
      staffing models and mentorship. Their proposal was approved, with courses set to
      resume in January, 2012.

PMID- 22398484
TI  - Nunavut: building nursing capacity.
AB  - Recruitment and retention issues associated with the growing nursing shortage in
      Canada are magnified in Nunavut, where the scope of nursing practice is much
      broader than in urban settings. The Qikiqtani General Hospital (QGH), a 35-bed
      hospital in Nunavut's capital, Iqaluit, was the home base for this multi-pronged
      pilot project that spanned 16 months to March 2011. The goals of the project
      included creating opportunities for front-line nurses to develop new clinical
      skills and knowledge and expand their competencies; offering enhanced critical
      care training relevant to the needs of nurses; and providing a smooth transition
      to entry to practice in a hospital setting for new graduate nurses. An in-house
      mentorship program was developed, and contracts were made with three outside
      parties: the Critical Care Education Network (CRI), the Ottawa Hospital and the
      Perinatal Partnership Program of Eastern and Southeastern Ontario. A number of
      professional development opportunities were provided - for example, 26 nurses
      participated in the CRI's critical care training, and six nurses were trained as
      CRI trainers.Overall, nurses were satisfied with the accessibility, delivery and
      applicability of the RTA education opportunities, and all nurses agreed that
      these opportunities increased their professional skills. A plan for the
      sustainability of the critical care portion of the Nunavut RTA project is
      currently in place, and the QGH is in the process of hiring a nurse educator for
      the hospital. This hiring will be a key piece to sustain the project initiatives.
      If the mentorship program is to continue, it will be essential to hire someone
      dedicated to the orientation of new graduates and new nurses.

PMID- 22398485
TI  - Staffing tool projects: introduction.

PMID- 22398486
TI  - Saskatchewan: improving patient, nursing and organizational outcomes utilizing
      formal nurse-patient ratios.
AB  - The issue of nurse-to-patient ratios has been of significant interest to nurses
      in Saskatchewan. A commitment to a nurse-to-patient pilot project was articulated
      in a letter of understanding in the 2005 to 2008 contract between the
      Saskatchewan Union of Nurses (SUN) and the Saskatchewan Association of Health
      Organizations. The SUN, the Saskatoon Health Region and the Saskatchewan Ministry
      of Health formed a partnership to engage in the pilot project, which lasted from
      November 2008 to March 2011. The project involved the creation of a flexible,
      dynamic and real-time staffing tool to inform day-to-day nurse staffing decisions
      on a hospital unit and was based on an adaptation of Curley's Synergy Model. A
      medical unit at St. Paul's Hospital in Saskatoon was selected for implementation,
      and all front-line nursing staff as well as unit nursing leaders were involved. A
      project working group adapted the Synergy-based Patient Scoring Tool (PST), which
      had been utilized for a recent project in British Columbia, to its own patient
      population. In April 2010, nurses began assessing each patient on every shift
      with the goal of determining the most suitable care provider. Patient assignment
      became based on the holistic assessment of patient needs according to the PST
      results rather than "geography" (for example, one nurse assigned to a multi-bed
      unit regardless of the acuity/capability of patients in the unit). Whenever
      possible, staffing on the unit was increased according to tool
      calculations.Positive impacts in patient outcomes began to be noted during the
      final data collection period for the project - nosocomial infection rates showed
      improvement, and the number of falls per patient-days decreased. As well, patient
      needs were made more visible through use of the PST, which created non
      threatening opportunities for dialogue related to legislated scopes of practice.
      While longer timelines and larger sample size are needed to measure impacts on
      retention and recruitment of nurses, nurses in the project demonstrated increased
      engagement over the study period. The tools and processes developed in this
      project are adaptable to other patient populations and care settings.

PMID- 22398487
TI  - Ontario: linking nursing outcomes, workload and staffing decisions in the
      workplace: the Dashboard Project.
AB  - Research shows that nurses want to provide more input into assessing patient
      acuity, changes in patient needs and staffing requirements. The Dashboard Project
      involved the further development and application of an electronic monitoring tool
      that offers a single source of nursing, patient and organizational information.
      It is designed to help inform nurse staffing decisions within a hospital setting.
      The Dashboard access link was installed in computers in eight nursing units
      within the Hamilton Health Sciences (HHS) network. The Dashboard indicators are
      populated from existing information/patient databases within the Decision Support
      Department at HHS. Committees composed of the unit manager, staff nurses, project
      coordinator, financial controller and an information controller met regularly to
      review the Dashboard indicators. Participants discussed the ability of the
      indicators to reflect their patients' needs and the feasibility of using the
      indicators to inform their clinical staffing plans. Project findings suggest that
      the Dashboard is a work in progress. Many of the indicators that had originally
      been incorporated were refined and will continue to be revised based on
      suggestions from project participants and further testing across HHS.
      Participants suggested the need for additional data, such as the time that nurses
      are off the unit (for code blue response, patient transfers and accompanying
      patients for tests); internal transfers/bed moves to accommodate patient-specific
      issues and particularly to address infection control issues; deaths and specific
      unit-centred data in addition to the generic indicators. The collaborative nature
      of the project enabled staff nurses and management to work together on a matter
      of high importance to both, providing valuable recommendations for shared nursing
      and interprofessional planning, further Dashboard development and project
      management.

PMID- 22398488
TI  - Evaluation project: introduction.

PMID- 22398489
TI  - Alberta: evaluation of nursing retention and recruitment programs.
AB  - Retention and recruitment strategies are essential to address nursing workforce
      supply and ensure the viability of healthcare delivery in Canada. Knowledge
      transfer between experienced nurses and those new to the profession is also a
      focus for concern. The Multi-Employer/United Nurses of Alberta Joint Committee
      attempted to address these issues by introducing a number of retention and
      recruitment (R&R) initiatives for nurses in Alberta: in total, seven different
      programs that were introduced to some 24,000 nurses and employers across the
      province of Alberta in 2001 (the Transitional Graduate Nurse Recruitment Program)
      and 2007 (the remaining six R&R programs). Approximately 1,600 nurses
      participated in the seven programs between 2001 and 2009. Of the seven
      strategies, one supported entry into the workplace, two were pre-retirement
      strategies and four involved flexible work options. This project entailed a
      retrospective evaluation of the seven programs and differed from the other
      Research to Action (RTA) projects because it was solely concerned with evaluation
      of pre-existing initiatives. All seven programs were launched without a formal
      evaluation component, and the tracking of local uptake varied throughout the
      province. The union and various employers faced challenges in implementing these
      strategies in a timely fashion, as most were designed at the bargaining table
      during negotiations. As a result, systems, policy and procedural changes had to
      be developed to support their implementation after they became
      available.Participants in the programs indicated improvements over time in
      several areas, including higher levels of satisfaction with work-life balance,
      hours worked and their current practice and profession. The evaluation found that
      participation led to perceived improvements in nurses' confidence, greater
      control over their work environment, decreased stress levels, increased energy
      and morale and perceived improved ability to provide high-quality care. However,
      no formal implementation plan had been developed or made available to assist
      employers with implementation of the programs. The findings highlight the need
      for more discipline in communicating, implementing and evaluating initiatives
      such as those evaluated retrospectively in this project. In particular, key
      performance indicators, baseline data, monitoring mechanisms and an evaluation
      plan need to be developed prior to implementation.

PMID- 22398490
TI  - Random acts of innovation: infiltrating silos and creating an interprofessional
      culture for quality care.

PMID- 22398491
TI  - Interprofessional education: an overview of key developments in the past three
      decades.
AB  - OBJECTIVE: This paper provides an overview of key developments of
      interprofessional education (IPE) in relation to its evolution over the past 30
      years. METHODS: A narrative review of the salient IPE literature was undertaken
      to generate key source materials for this paper. RESULTS: Results are presented
      in four sections that focus on describing and discussing: the emergence of IPE,
      different learning/teaching approaches; the evidence base for IPE; organizational
      elements. In addition, to help illustrate these developments, we offer a case
      example of the work currently being undertaken at our own institution, with a
      focus on how various IPE developments have been integrated into our
      organizational priorities. CONCLUSIONS: Based on the results presented, a series
      of key conclusions for the future development and implications of IPE are
      outlined.

PMID- 22398492
TI  - Relational learning and interprofessional practice: transforming health education
      for the 21st century.
AB  - Theories and traditions emphasizing the centrality of caring have guided the
      evolution of the healthcare professions. In contemporary practice, creating a
      therapeutic context in which healing can occur relies not just on the caring
      dispositions of individual clinicians, but also on the collective relational
      capacities of interprofessional healthcare teams. This article describes the
      intersection and complementarity of relational and interprofessional learning
      approaches to health education, provides exemplars of shared learning models and
      discusses the benefits and obstacles to integrating relational and
      interprofessional philosophies into real world practice.

PMID- 22398493
TI  - Models in interprofessional education: the IP enhancement approach as effective
      alternative.
AB  - OBJECTIVE: This article discusses the strategies and challenges of implementing
      interprofessional education interventions with students from different
      disciplines. It reviews two models of interprofessional education in academic
      prelicensure curricula including the extra-curricular and the crossbar models by
      considering ease of implementation, program reach and sustainability. It also
      introduces the interprofessional enhancement approach as an additional curriculum
      development strategy. RESULTS: The Alberta Interprofessional Education for
      Collaborative Patient-Centred Practice project used the Interprofessional
      Enhancement Approach by integrating course content into existing placement
      courses for nursing, respiratory therapy, pharmacy, and physiotherapy students.
      The students conducted their regular discipline-specific placements at various
      clinical sites in southern Alberta, Canada that were supplemented by three
      interprofessional strategies: mentoring, workshops and online discussions. The
      intervention reached over sixty individuals including students, preceptors and
      faculty. CONCLUSION: As compared to other approaches (extra-curricular and
      crossbar models), this approach shows that IP course content can be added to
      placement courses without restructuring complete curricula. This article intends
      to initiate further discussions about different IP education models in
      prelicensure education.

PMID- 22398494
TI  - Building a sustainable academic-community partnership: focus on fall prevention.
AB  - OBJECTIVE: To create an interprofessional/interdisciplinary education (IPE),
      pilot course that provided a representative group of students the opportunity to
      develop a 6 week fall reduction program for a group of elder volunteers who were
      independently living in the community. The authors describe the processes that
      occurred for the course and student-led program to be developed. RESULTS: This
      pilot course provided opportunities for interprofessional student learning,
      faculty practice and development, and a program to improve the health of the
      participants. Sustaining interprofessional collaboration is challenging,
      primarily due to scheduling difficulties and faculty workloads. CONCLUSIONS: More
      time needs to be devoted to developing the team skills of students, as well as
      building their knowledge of the contributions each discipline can make to a
      holistic view of elders. The next phase of this project needs to include pre and
      post measurement of students' readiness for IPE and elders to more adequately
      assess the components and effects of the course and program for fall prevention.

PMID- 22398495
TI  - Preparing rehabilitation healthcare providers in the 21st century: implementation
      of interprofessional education through an academic-clinical site partnership.
AB  - OBJECTIVE: Health profession education programs often struggle with barriers to
      implementing interprofesssional educational (IPE) initiatives, limiting early and
      consistent exposure of students to core IPE competencies. Few published reports
      are available to guide the implementation of IPE programs into practice. This
      article describes a successful and evolving partnership between an independent
      university and a tertiary care hospital. The IPE goals of this partnership were
      to expose students to roles of other disciplines in the complex hospital
      environment and integrate acute care exposure throughout the Doctor of Physical
      Therapy and Master of Science in Occupational Therapy curricula. RESULTS: Faculty
      and students, patients and families, and occupational and physical therapy
      clinicians participated in a series of learning activities in an acute care
      setting involving interprofessional teams of students. Activities included
      observations of OT and PT clinicians providing standard patient care, practice
      conducting team patient interviews, and interactive treatment planning sessions
      conducted live via videoconferencing technology between a patient's hospital room
      and an academic classroom on the university campus. The activities generally were
      designed to improve student preparedness for working as part of an
      interprofessional team in an acute care setting. CONCLUSIONS: Student and
      clinician feedback support the early development of student IPE competencies,
      including the appreciation and understanding of professional roles in the team
      approach to patient care and the development of effective communication skills.
      The partnership between the academic institution and tertiary care hospital is an
      effective vehicle to deliver and sustain IPE educational initiatives in the acute
      care setting. Current and planned IPE curriculum integration are discussed along
      with a preliminary analysis of IPE outcomes.

PMID- 22398496
TI  - Undergraduate students trained to provide basic health care screening in an
      underserved community: a door-to-door campaign.
AB  - OBJECTIVE: Millions of Americans fail to receive proper preventative care and/or
      have poorly managed chronic conditions. The purpose of this study was to
      determine if local student volunteers could be utilized to assess hypertension in
      an underserved community. The two primary objectives included first determining
      if student volunteers could be effectively trained to perform blood pressure
      screening and if they could then successfully provide such screening door-to-door
      in a targeted community. RESULTS: Volunteers were recruited from local
      universities, trained and skill tested in basic medical techniques and simulated
      door-to-door interactions. Of 43 initial students, 37 successfully completed
      written and competency exams. During the two-weekend community engagement, 220
      individuals answered door knocks and 80 agreed to screening. Of those without a
      previous diagnosis of hypertension, 70.9% had an abnormal reading as did 87% of
      those who had been previously diagnosed with hypertension. This methodology was
      implemented at minimal cost and was perceived as a benefit by both students and
      community members. CONCLUSIONS: The study scope did not allow longer-term follow
      up for those with abnormal readings, but did serve as a reminder for those
      diagnosed with hypertension to monitor their status and as an indication for
      those undiagnosed that they may need to seek further care. Our findings are
      important because they show that undergraduate students are a viable source of
      volunteers for performing medically-related community outreach.

PMID- 22398497
TI  - Turf, team, and town: a geriatric interprofessional education program.
AB  - OBJECTIVE AND PARTICIPANTS: This program provides an interprofessional course to
      students, allowing them to learn together with each other and their elder
      teachers. GOALS: include refining their professional parameters (turf), learning
      how to successfully collaborate with other professionals (team), and determining
      how to effectively design intervention plans for elders within their own
      communities (town). Various methods of evaluation, such as journals,
      participation in rounds, and OSCEs, used to assess students' status are
      described. RESULTS: Both students and faculty gained clearer perceptions of other
      professions through their work with each other and the ability to more
      effectively communicate with other profession. Both also learned, through their
      relationships with their elder teachers, more about how their specific
      professions' contributions can affect elders and how elders perceive and
      contribute to their own communities. CONCLUSIONS: This program has been a
      successful venture. The challenge is now to devise a way to provide similar
      experiences to a larger group of students.

PMID- 22398498
TI  - Fostering the development of effective person-centered healthcare communication
      skills: an interprofessional shared learning model.
AB  - OBJECTIVE: To describe the implementation of an interprofessional shared learning
      model designed to promote the development of person-centered healthcare
      communication skills. PARTICIPANTS: Master of social work (MSW) and doctor of
      physical therapy (DPT) degree students. METHODS: The model used evidence-based
      principles of effective healthcare communication and shared learning methods; it
      was aligned with student learning outcomes contained in MSW and DPT curricula.
      Students engaged in 3 learning sessions over 2 days. Sessions involved
      interactive reflective learning, simulated role-modeling with peer assessment,
      and context-specific practice of communication skills. The perspective of
      patients/clients was included in each learning activity. Activities were
      evaluated through narrative feedback. RESULTS: Students valued opportunities to
      learn directly from each other and from healthcare consumers. Important insights
      and directions for future interprofessional learning experiences were gleaned
      from model implementation. CONCLUSIONS: The interprofessional shared learning
      model shows promise as an effective method for developing person-centered
      communication skills.

PMID- 22398500
TI  - Health work in the home.

PMID- 22398499
TI  - Transcultural healthcare immersion: a unique interprofessional experience poised
      to influence collaborative practice in cultural settings.
AB  - OBJECTIVE: This paper describes a model for interprofessional and transcultural
      learning established by the author and supported by the University of New England
      and Ghana Health Mission, Inc. The model for interprofessional immersion in
      cultural settings represents a guiding framework predicated on a conceptual
      "brick and mortar" process for building cultural proficiency among individuals
      and within teams. It encompasses social, clinical and behavioral components
      (brick) and personal desire, cultural humility and values (mortar). The
      ''bounty'' aspect of the model is achieved by way of successful student learning
      outcomes, positive interprofessional and community-based collaborations, and
      finally, and to be measured over time, favorable patient and population
      (programmatic) outcomes. RESULTS: In partnership with the Ghana Health Mission,
      Inc and local community health workers, students and faculty from a range of
      health professions took part in a cultural-clinical experience known as
      Transcultural Immersion in Healthcare. The goal of the experience was to advance
      cultural proficiency and knowledge through intensive cultural immersion. An urban
      setting in Ghana, located in West Africa served as the setting for this unique
      experience. CONCLUSION: The transcultural immersion in healthcare experience
      achieved its ''bounty'' as seen in the enhanced cultural proficiency of students
      and faculty, seamless interprofessional communication and collaboration, and
      provision of primary care and related services to patients and the Ghanaian
      community. Future research is in development to test the Model for
      Interprofessional Immersion in Cultural Settings (MIICS) in a variety of other
      settings and with a cross section of health disciplines.

PMID- 22398501
TI  - Health information management in the home: a human factors assessment.
AB  - OBJECTIVE: Achieving optimal health outcomes requires that consumers maintain
      myriad health data and understand how to utilize appropriate health information
      management applications. This case study investigated four families' health
      information management tasks in their homes. PARTICIPANTS: Four different
      families participated in the study: a single parent household; two nuclear family
      households; and an extended family household. METHODS: A work system model known
      as the balance model was used as a guiding framework for data collection. Data
      collection consisted of three stages: (1) primary health information manager
      interviews; (2) family interviews; and (3) task observations. RESULTS: Overall,
      families reported 69 unique health information management tasks that took place
      in nine different locations, using 22 different information storage artifacts.
      Frequently occurring tasks related to health management or health coordination
      were conducted in public spaces. Less frequent or more time-consuming tasks, such
      as researching a health concern or storing medical history, were performed in
      private spaces such as bedrooms or studies. CONCLUSIONS: Similarities across
      households suggest potential foundational design elements that consumer health
      information technology application designers need to balance with tailored
      interventions to successfully support variations in individuals' health
      information management needs.

PMID- 22398502
TI  - RareICT: a web-based resource to augment self-care and independence with a rare
      medical condition.
AB  - OBJECTIVE: Everyday challenges to "live well" with a rare disorder, anorectal
      anomaly, was the starting point to design a social-software environment, called
      RareICT, to help patients and family members in their everyday, additional un
      paid work. PARTICIPANTS: Persons with the rare disorder, family members and
      health providers were recruited to elaborate challenges to daily living given
      this condition. METHODS: An exploratory study was designed, and we set up a
      series of participatory design workshops to explore challenges to everyday living
      with a rare medical condition. RESULTS: Anorectal anomaly has few visible outward
      signs, and is often surrounded with secrecies. Findings shed light on efforts to
      maintain physical functioning, psychosocial and emotional wellbeing. For an
      affected person to "live well" modifications to everyday routines, along with
      management work, support work and planning work are required. Accumulating
      practical strategies, everyday experiences and knowledge, along with virtual
      access to peers may augment such health maintenance work if integrity,
      accountability and trust, confidentiality and privacy are maintained. CONCLUSION:
      A social-software environment was set up to offer co-evolving content and augment
      health-related decision-making at home. To evaluate the project will focus on
      interest in maintaining participation determined and how users benefit from
      services such as RareICT.

PMID- 22398503
TI  - Evaluation of a volunteer-led in-home exercise program for home-bound older
      adults.
AB  - OBJECTIVE: Exercise programs have been found to have substantial benefits for
      older persons, but implementing these programs with frail homebound seniors is
      challenging. The project team aimed to evaluate an in-home exercise program for
      older adults--the Victorian Order of Nurses' for Canada's SMART (Seniors
      Maintaining Active Roles Together)(r) (VON SMART(r)) In-Home Exercise Program- in
      which the exercises are led by trained volunteers. The majority of volunteers
      were females who exercise regularly. Over half of the volunteers were 60 years of
      age or older, and over half had had prior health or fitness training. Volunteers
      reported receiving multiple benefits from performing their role as an exercise
      leader. PARTICIPANTS: From January to August, 2009, a total of 59 volunteers,
      seven Site Coordinators, and 33 home-bound older (mean age: 80 years; SD: 8.8)
      clients from eight VON sites and one partner organization participated in the
      evaluation. METHODS: Data collection included pre-post quantitative measures of
      participants' physical function, satisfaction surveys of participants, follow up
      semi-structured interviews of participants, feedback surveys of volunteers and
      site coordinators, and a focus group interview of site coordinators. RESULTS: The
      Chair Stand test (p<0.001), the Reaching Forward test (p=0.028), the Activities
      Balance Confidence Scale (p=0.02), as well as measures of activities of daily
      living (ADL) inside the home (p=0.001) and outside the home (p=0.009) showed
      significant improvement. CONCLUSIONS: This evaluation showed that the exercises
      improved participants' strength, flexibility, balance, and ability to perform
      ADL. This study provides additional evidence of the benefits of in-home exercise
      for frail seniors, and supports a role for volunteers in delivering these
      programs. The volunteers reported receiving social benefits of meeting new
      people, being able to see the difference they helped make in others, as well as
      personal physical benefits from exercising more.

PMID- 22398504
TI  - Creating employment opportunities for people with disabilities in healthcare: the
      Bristol Employment Collaborative.
AB  - Unemployment is a significant problem among working-age adults with disabilities.
      The Bristol Employment Collaborative (BEC), one of five Regional Employment
      Collaboratives in Massachusetts, brings together State agencies, community
      employment service providers, educational institutions, local businesses,
      economic development organizations, and people with disabilities to design and
      implement regional strategies to enhance employment opportunities and outcomes
      for people with disabilities. Launched in 2009, BEC has developed an innovative
      model to train people with disabilities to become personal assistance services
      workers, a healthcare occupation with high demand. The case study describes the
      strategic planning process undertaken by BEC partners to develop a certificate
      program to be offered by the local community college. The first class enrolled in
      September 2010 and graduated ten weeks later. Innovative approaches such as the
      one being pursued and developed by the BEC could help address both unemployment
      for people with disabilities and the labor shortages in the healthcare sector.

PMID- 22398505
TI  - Medical devices in the home: a unique challenge for the FDA.
AB  - OBJECTIVE: With the rising numbers of elderly populations and those with chronic
      diseases, the Home Healthcare field has inevitable expanded within the United
      States. Patients, more specifically home-bound patients, are becoming
      increasingly dependent on medical technology to help sustain and improve their
      quality if life. Often times, home care patients, or care recipients, depend on a
      properly functioning medical device for recovery. As efficient as this method may
      be, home healthcare also comes along with many challenges involving use and
      management of medical devices. Difficulties regarding device function, use, the
      environment, and human factors can all serve as factors to jeopardize patient
      safety. FDA recognizes that devices need to be safe and capable of meeting needs
      in an uncontrolled home environment. PARTICIPANTS: Major stakeholders such as
      manufacturers, distributors, human factor specialists, professional health
      organizations, healthcare professionals, patient/caregivers, and other government
      agencies. RESULT: FDA would assure that manufacturers are designing and testing
      devices for the home, that proper training and education to use the device are
      available and completed, and the public knows how to report problems with their
      devices. METHODS: FDA launched the Medical Device Home Use Initiative in April
      2010 which proposed different methods that can support safety and safe use of
      medical devices in the home environment. CONCLUSION: FDA faces many challenges in
      assuring safe usage of medical devices in the home. FDA hopes that stakeholders
      can also become actively involved in working with us to address a total life
      cycle approach on device safety.

PMID- 22398506
TI  - Fast separations by capillary electrophoresis hyphenated to electrospray
      ionization time-of-flight mass spectrometry as a tool for arsenic speciation
      analysis.
AB  - Fast capillary electrophoresis (CE) hyphenated to time-of-flight mass
      spectrometry (TOF-MS) of four organoarsenic species (glycerol oxoarsenosugar,
      sulfate oxoarsenosugar, arsenobetaine, arsenocholine) are presented using short
      length CE capillaries under high electric field strengths of up to 1.3 kV cm(-1)
      with small inner diameter (ID). The separation of arsenosugars by CE is
      demonstrated for the first time. An aqueous formic acid solution was employed as
      the background electrolyte (BGE) for the separation. Various acid concentrations
      were evaluated for their influence on migration times, separation efficiency as
      well as with regard to controlling the charge of the arsenic species. A 0.1 M
      formic acid/ammonium formate buffer (pH 2.8) proved to be suitable for the
      separation of the four species. A non-aqueous BGE was tested as an alternative
      buffer system for fast speciation analysis. Separation of arsenobetaine and
      arsenocholine could even be achieved within 10 s by pressure-assisted CE.
      Application of the optimized method for the analysis of extracts of a seagrass
      and a Wakame algae sample as well as the brown algae homogenate reference
      material IAEA-140/TM revealed a clear signal for the glycerol arsenosugar.

PMID- 22398508
TI  - Is a population-level physical activity legacy of the London 2012 Olympics
      likely?

PMID- 22398507
TI  - The homozygous p.C1024R- ADAMTS13 gene mutation links to a late-onset phenotype
      of Upshaw-Schulman syndrome in Japan.

PMID- 22398509
TI  - Role of substance abuse comorbidity and personality on the outcome of depression
      in bipolar disorder: harm avoidance influences medium-term treatment outcome.
AB  - Comorbid conditions are frequent in bipolar disorder (BD) and may complicate the
      treatment and course of illness. We investigated the role of substance use
      disorder (SUD), axis II personality disorders (PD) and continuous personality
      traits on the medium-term outcome (6 months) of treatment for bipolar depression.
      One hundred and thirty-nine BD patients meeting criteria for a depressive episode
      were included in the study. SUD and PD were diagnosed according to structured
      interviews. Personality dimensions were evaluated by the Temperament and
      Character Inventory. Depressive severity over time was evaluated by the Hamilton
      Rating Scale for Depression. Neither PD nor SUD influenced the outcome of
      depression. Variables independently associated with a poor outcome were a high
      baseline severity and high scores for the temperamental trait of Harm Avoidance.
      Though several limitations characterize the present study, neurotic personality
      traits seem to be associated with a slower recovery from depressive symptoms in
      BD, independently from their initial severity.

PMID- 22398510
TI  - Selective lymph node dissection for castration-resistant prostate cancer.
AB  - BACKGROUND: No relevant data have been published on the impact of retroperitoneal
      lymph node dissection (LND) on clinical outcome in patients with castration
      resistant prostate cancer. METHODS: We retrospectively studied the records of 6
      patients with lymph node metastases from castration-resistant prostate cancer who
      underwent a retroperitoneal LND between 2005 and 2010. Complication rate and
      clinical outcome were examined. RESULTS: Mean patient age was 69.2 (63-81) years.
      Primary therapy was radical prostatectomy, radiation therapy, or pelvic LND and
      androgen deprivation in 3, 2 and 1 cases, respectively. Mean prostate-specific
      antigen (PSA) at LND was 37.6 (20.3-139) ng/dl. LND was performed as a modified
      unilateral (n = 3), bilateral (n = 1) and bilateral extended (n = 2) approach
      with a median lymph node density of 0.739 (0.111-1). Preoperative Charlson index
      was 0 (n = 3) or 1 (n = 3). No intra- or postoperative complications occurred.
      The average postoperative decline of PSA was 39.3% (-99.4 to +31.3). Differences
      between mean pre- and postoperative PSA velocities and densities were 23.9
      ng/ml/year and 11.2 months, respectively (p = 0.24 and p = 0.40). Four patients
      (67%) developed bone metastases after a mean period of 23.5 (5-58) months. Median
      bone metastases-free survival was 15.5 months and median overall survival after
      LND was 31.7 months on Kaplan-Meier analysis. CONCLUSIONS: A selective LND in
      castration-resistant prostate cancer patients could be safely performed. A
      positive effect on the PSA and PSA kinetics was accomplished for the majority of
      patients. This new surgical approach represents an alternative treatment option
      in the palliative setting of prostate cancer patients and could delay toxic
      systemic therapy up to 12 months.

PMID- 22398511
TI  - Unique genomic structure and distinct mitotic behavior of ring chromosome 21 in
      two unrelated cases.
AB  - A ring chromosome replacing a normal chromosome could involve variable structural
      rearrangements and mitotic instability. However, most previously reported cases
      lacked further genomic characterization. High-resolution oligonucleotide array
      comparative genomic hybridization with single-nucleotide polymorphism typing
      (aCGH+SNP) was used to study 2 unrelated cases with a ring chromosome 21. Case 1
      had severe myopia, hypotonia, joint hypermobility, speech delay, and dysmorphic
      features. aCGH detected a 1.275-Mb duplication of 21q22.12-q22.13 and a 6.731-Mb
      distal deletion at 21q22.2. Case 2 showed severe growth and developmental
      retardations, intractable seizures, and dysmorphic features. aCGH revealed a
      contiguous pattern of a 3.612- Mb deletion of 21q22.12-q22.2, a 4.568-Mb
      duplication of 21q22.2-q22.3, and a 2.243-Mb distal deletion at 21q22.3. Mitotic
      instability was noted in 13, 30, and 76% of in vitro cultured metaphase cells,
      interphase cells, and leukocyte DNA, respectively. The different phenotypes of
      these 2 cases are likely associated with the unique genomic structure and
      distinct mitotic behavior of their ring chromosome 21. These 2 cases represent a
      subtype of ring chromosome 21 probably involving somatic dicentric ring breakage
      and reunion. A cytogenomic approach is proposed for characterizing the genomic
      structure and mitotic instability of ring chromosome abnormalities.

PMID- 22398513
TI  - Pt nanoparticles decorated with a discrete number of DNA molecules for
      programmable assembly of Au-Pt bimetallic superstructures.
AB  - Discrete DNA decorations of Pt nanoparticles (PtNPs) are realized for the first
      time, which provide a valence control over the quasi-molecular self-assembly of
      Au-Pt bimetallic heteronanostructures with DNA as the guide.

PMID- 22398515
TI  - Lessons of a triple disaster.

PMID- 22398514
TI  - Brain plasticity, sleep and aging.
AB  - The link between sleep and aging is a hot topic of research. On the one hand,
      much attention has been paid to epidemiological studies showing that both short
      sleep and long sleep in humans are associated with reduced longevity. I will
      briefly review this literature and discuss recent experiments in the fruit fly
      Drosophila melanogaster that may contribute to understanding this complicated
      association. On the other hand, other experiments have focused on age-related
      sleep changes. Sleep quantity and quality tend to decrease with age, but the
      underlying mechanisms remain unclear. In young subjects, converging evidence from
      human and animal studies shows that the need for sleep is strongly modulated by
      the amount of brain plasticity during prior wake. In short, the more we learn and
      adapt our brain to an ever-changing environment, the more we need to sleep. If
      so, poor sleep in the elderly could be caused by a chronic decrease in sleep need
      due to reduced opportunity to learn and be exposed to novel experiences, rather
      than, or in addition to, an intrinsic problem in the neural circuits responsible
      for sleep regulation. This distinction has obvious practical implications.
      However, very little research has been done on this topic.

PMID- 22398516
TI  - Political science.

PMID- 22398517
TI  - Gold in the text?

PMID- 22398518
TI  - No theory is too special to question.

PMID- 22398529
TI  - Cuts hamper bid to tackle AIDS.

PMID- 22398530
TI  - A solid case for Majorana fermions.

PMID- 22398531
TI  - Laser fusion nears crucial milestone.

PMID- 22398532
TI  - Trouble at the text mine.

PMID- 22398533
TI  - The Japanese tsunami: After shock.

PMID- 22398534
TI  - Japan's nuclear crisis: Fukushima's legacy of fear.

PMID- 22398535
TI  - Rebuilding Japan: After the deluge.

PMID- 22398536
TI  - Tsunami forecasting: The next wave.

PMID- 22398537
TI  - Earthquake hazards: Putting seismic research to most effective use.

PMID- 22398538
TI  - Seismology: Why giant earthquakes keep catching us out.

PMID- 22398539
TI  - Energy policy: The nuclear landscape.

PMID- 22398544
TI  - Genetics research: Clinical standards not practical in the lab.

PMID- 22398545
TI  - Future pandemics: Step up funding for flu prevention.

PMID- 22398546
TI  - Sugar: an excess of anything can harm.

PMID- 22398547
TI  - Degraded ecosystems: Keep jellyfish numbers in check.

PMID- 22398548
TI  - Social science: Human reproductive assistance.

PMID- 22398549
TI  - Physical chemistry: Single molecules filmed dancing on a table top.

PMID- 22398551
TI  - Cell biology: The sensation of stretch.

PMID- 22398552
TI  - Genomics: Gorilla gorilla gorilla.

PMID- 22398553
TI  - Geochemistry: A rusty carbon sink.

PMID- 22398554
TI  - Materials science: Continuity through dispersity.

PMID- 22398556
TI  - Experimental verification of Landauer's principle linking information and
      thermodynamics.
AB  - In 1961, Rolf Landauer argued that the erasure of information is a dissipative
      process. A minimal quantity of heat, proportional to the thermal energy and
      called the Landauer bound, is necessarily produced when a classical bit of
      information is deleted. A direct consequence of this logically irreversible
      transformation is that the entropy of the environment increases by a finite
      amount. Despite its fundamental importance for information theory and computer
      science, the erasure principle has not been verified experimentally so far, the
      main obstacle being the difficulty of doing single-particle experiments in the
      low-dissipation regime. Here we experimentally show the existence of the Landauer
      bound in a generic model of a one-bit memory. Using a system of a single
      colloidal particle trapped in a modulated double-well potential, we establish
      that the mean dissipated heat saturates at the Landauer bound in the limit of
      long erasure cycles. This result demonstrates the intimate link between
      information theory and thermodynamics. It further highlights the ultimate
      physical limit of irreversible computation.

PMID- 22398557
TI  - Field-driven photoemission from nanostructures quenches the quiver motion.
AB  - Strong-field physics, an extreme limit of light-matter interaction, is expanding
      into the realm of surfaces and nanostructures from its origin in atomic and
      molecular science. The attraction of nanostructures lies in two intimately
      connected features: local intensity enhancement and sub-wavelength confinement of
      optical fields. Local intensity enhancement facilitates access to the strong
      field regime and has already sparked various applications, whereas spatial
      localization has the potential to generate strong-field dynamics exclusive to
      nanostructures. However, the observation of features unattainable in gaseous
      media is challenged by many-body effects and material damage, which arise under
      intense illumination of dense systems. Here, we non-destructively access this
      regime in the solid state by employing single plasmonic nanotips and few-cycle
      mid-infrared pulses, making use of the wavelength-dependence of the interaction,
      that is, the ponderomotive energy. We investigate strong-field photoelectron
      emission and acceleration from single nanostructures over a broad spectral range,
      and find kinetic energies of hundreds of electronvolts. We observe the transition
      to a new regime in strong-field dynamics, in which the electrons escape the
      nanolocalized field within a fraction of an optical half-cycle. The transition
      into this regime, characterized by a spatial adiabaticity parameter, would
      require relativistic electrons in the absence of nanostructures. These results
      establish new degrees of freedom for the manipulation and control of electron
      dynamics on femtosecond and attosecond timescales, combining optical near-fields
      and nanoscopic sources.

PMID- 22398555
TI  - Insights into hominid evolution from the gorilla genome sequence.
AB  - Gorillas are humans' closest living relatives after chimpanzees, and are of
      comparable importance for the study of human origins and evolution. Here we
      present the assembly and analysis of a genome sequence for the western lowland
      gorilla, and compare the whole genomes of all extant great ape genera. We propose
      a synthesis of genetic and fossil evidence consistent with placing the human
      chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and
      10 million years ago. In 30% of the genome, gorilla is closer to human or
      chimpanzee than the latter are to each other; this is rarer around coding genes,
      indicating pervasive selection throughout great ape evolution, and has functional
      consequences in gene expression. A comparison of protein coding genes reveals
      approximately 500 genes showing accelerated evolution on each of the gorilla,
      human and chimpanzee lineages, and evidence for parallel acceleration,
      particularly of genes involved in hearing. We also compare the western and
      eastern gorilla species, estimating an average sequence divergence time 1.75
      million years ago, but with evidence for more recent genetic exchange and a
      population bottleneck in the eastern species. The use of the genome sequence in
      these and future analyses will promote a deeper understanding of great ape
      biology and evolution.

PMID- 22398558
TI  - Imaging ultrafast molecular dynamics with laser-induced electron diffraction.
AB  - Establishing the structure of molecules and solids has always had an essential
      role in physics, chemistry and biology. The methods of choice are X-ray and
      electron diffraction, which are routinely used to determine atomic positions with
      sub-angstrom spatial resolution. Although both methods are currently limited to
      probing dynamics on timescales longer than a picosecond, the recent development
      of femtosecond sources of X-ray pulses and electron beams suggests that they
      might soon be capable of taking ultrafast snapshots of biological molecules and
      condensed-phase systems undergoing structural changes. The past decade has also
      witnessed the emergence of an alternative imaging approach based on laser-ionized
      bursts of coherent electron wave packets that self-interrogate the parent
      molecular structure. Here we show that this phenomenon can indeed be exploited
      for laser-induced electron diffraction (LIED), to image molecular structures with
      sub-angstrom precision and exposure times of a few femtoseconds. We apply the
      method to oxygen and nitrogen molecules, which on strong-field ionization at
      three mid-infrared wavelengths (1.7, 2.0 and 2.3 MUm) emit photoelectrons with a
      momentum distribution from which we extract diffraction patterns. The long
      wavelength is essential for achieving atomic-scale spatial resolution, and the
      wavelength variation is equivalent to taking snapshots at different times. We
      show that the method has the sensitivity to measure a 0.1 A displacement in the
      oxygen bond length occurring in a time interval of ~5 fs, which establishes LIED
      as a promising approach for the imaging of gas-phase molecules with unprecedented
      spatio-temporal resolution.

PMID- 22398559
TI  - Preservation of organic matter in sediments promoted by iron.
AB  - The biogeochemical cycles of iron and organic carbon are strongly interlinked. In
      oceanic waters, organic ligands have been shown to control the concentration of
      dissolved iron. In soils, solid iron phases shelter and preserve organic carbon,
      but the role of iron in the preservation of organic matter in sediments has not
      been clearly established. Here we use an iron reduction method previously applied
      to soils to determine the amount of organic carbon associated with reactive iron
      phases in sediments of various mineralogies collected from a wide range of
      depositional environments. Our findings suggest that 21.5 +/- 8.6 per cent of the
      organic carbon in sediments is directly bound to reactive iron phases. We further
      estimate that a global mass of (19-45) * 10(15) grams of organic carbon is
      preserved in surface marine sediments as a result of its association with iron.
      We propose that these associations between organic carbon and iron, which are
      formed primarily through co-precipitation and/or direct chelation, promote the
      preservation of organic carbon in sediments. Because reactive iron phases are
      metastable over geological timescales, we suggest that they serve as an efficient
      'rusty sink' for organic carbon, acting as a key factor in the long-term storage
      of organic carbon and thus contributing to the global cycles of carbon, oxygen
      and sulphur.

PMID- 22398562
TI  - Heteroatom-directed Wacker oxidations. A protection-free synthesis of (-)
      heliophenanthrone.
AB  - The first enantioselective six-step synthesis of (-)-heliophenanthrone has been
      achieved without any protection-deprotection protocol at an overall yield of 28%.
      Key features of this synthesis comprise a heteroatom-directed Wacker oxidation of
      an internal cyclic olefin in addition to asymmetric Brown allylation and ring
      closing metathesis (RCM).

PMID- 22398563
TI  - Road to fulfilment: taming the immune response to restore vision.
AB  - While traditionally considered to be an immune privileged site, the eye, and in
      particular the retina, is nonetheless endowed with immune-competent cells capable
      of engaging powerful immune regulatory networks. By understanding the mechanisms
      that promote immune well-being in the eye, we are able to generate therapies
      which combat undue immune-mediated damage not only by revealing mechanisms that
      promote tissue damage, but also by an ability to restore tissue immune
      homeostasis by harnessing intrinsic immune-regulatory mechanisms. The result is
      to maintain or restore immune health as well as combat tissue damage evoked
      during, for example, intra-ocular inflammatory disease (uveitis), angiogenesis
      (age-related macular degeneration) and retinal degenerative disorders. Immune
      activation and regulation is a balance that is dictated by cognate and soluble
      factors at both a tissue and cellular level. These continuously respond to and
      eradicate danger and pathogenic signals whilst maintaining tissue function by
      controlling, and not exclusively, vascular barriers, complement activation,
      macrophage activation and keeping in check local T cell proliferation. Loss of
      the balance between activation and inhibitory signals leads to uncontrolled
      tissue damage. Understanding the mechanisms has gained potential therapeutic
      opportunities not only to suppress on-going inflammation, but also to restore
      homeostasis and prevent recrudescence.

PMID- 22398565
TI  - Short-term eltrombopag for surgical preparation of a patient with inherited
      thrombocytopenia deriving from MYH9 mutation.

PMID- 22398564
TI  - Apolipoprotein E epsilon4 status modifies the effects of sex hormones on
      neuropsychiatric symptoms of Alzheimer's disease.
AB  - BACKGROUND: Studies on the associations between sex hormones and multiple
      neuropsychiatric symptoms of Alzheimer's disease (AD) are lacking. Apolipoprotein
      E (APOE) epsilon4 status may modify the effects of sex hormones on
      neuropsychiatric symptoms. METHODS: A total of 86 male and 87 female AD patients
      participated in the present study. The adjusted associations between symptoms on
      the Neuropsychiatric Inventory and serum levels of estradiol (total,
      bioavailable) and testosterone (total, bioavailable) were analyzed. RESULTS:
      Agitation/aggression was negatively associated with quartiles of bioavailable
      estradiol among male patients, and positively associated with testosterone levels
      among female patients. The modifying effects of APOE genotype only existed in
      female patients. Those females with higher levels of estradiol and the epsilon4
      allele had higher odds of agitation/aggression. Furthermore, the testosterone *
      APOE epsilon4 status interaction was positively associated with hallucinations in
      female patients. CONCLUSION: There were sex-specific effects of sex hormones on
      agitation/aggression in AD. Sex hormones and APOE epsilon4 status synergistically
      influence some neuropsychiatric symptoms among female but not male AD patients.

PMID- 22398566
TI  - Intercomparison of three recruitment maneuvers in acute respiratory distress
      syndrome: the role of Body Mass Index.
AB  - BACKGROUND: The aim of this paper was to investigate the effectiveness of three
      different recruitment maneuvers (RMs) on respiratory and hemodynamic indexes, in
      patients with acute respiratory distress syndrome (ARDS), and determine the
      impact of patients' body mass index (BMI) on RMs efficacy. METHODS: This was a
      prospective clinical trial conducted in a general intensive care unit. In 25
      consecutive early ARDS patients arterial blood gases, respiratory system
      elastance (Est,rs) and hemodynamics were monitored before (T(0)), and at 3, 15,
      and 30 min (T(3), T(15), T(30), respectively) after each of three different RMs
      techniques with same airway pressures (45 cmH(2)O), randomly applied in each
      patient; RM-1: pressure control ventilation for 1 min, RM-2: two hyperinflations
      with continuous positive airway pressure for 20 sec and 1 min interval in
      between, RM-3: three consecutive sighs. RESULTS: All RMs improved oxygenation and
      Est,rs shortly (T(3)) after their application, but only RM-2 had a prolonged
      beneficial effect on oxygenation (T(30)). Patients were further divided according
      to their BMI: in the low BMI group (<27.3 Kg/m(2)) the effectiveness of RMs was
      similar to the whole study population, while in the high BMI group (>= 27.3
      Kg/m(2)) no sustained effect followed any RM. CONCLUSION: In our cohort,
      recruitment by two sustained inflations resulted in a more persistent improvement
      of oxygenation as compared with recruitment by pressure controlled ventilation or
      consecutive sighs with the same airway pressure. BMI seems to have an impact on
      RMs effectiveness, most probably by altering the effective transpulmonary
      pressure. More studies are required to elucidate this observation.

PMID- 22398567
TI  - Diagnostic value of specific IgE analysis in latex allergy.
AB  - BACKGROUND: The precision of the methods used to diagnose latex allergy is of
      great importance due to false-positive results. Neither the skin prick test (SPT)
      nor the latex-specific IgE assay has 100% diagnostic accuracy. We analysed the
      diagnostic value of latex-specific IgE by the first-ever concomitant use of the
      SPT and nasal provocation test (NPT). METHODS: Twenty-seven latex-sensitive
      patients (group 1), 46 aeroallergen-sensitive patients (group 2a) and 33 healthy
      subjects (group 2b) participated in the study. All groups underwent an SPT with
      latex and aeroallergens and an NPT with latex. Latex-specific IgE and total IgE
      levels were measured by the ImmunoCAP assay. RESULTS: Latex-specific IgE was
      positive in 92.6, 30.4 and 9.1% of groups 1, 2a and 2b, respectively. The 11
      aeroallergen-sensitive patients in group 1 and all of the patients in group 2a
      were predominantly sensitised to pollens (grass, weed and tree) and reacted to a
      lesser degree to house dust mite, moulds and animal dander. Combined pollinosis
      was remarkably more prevalent in patients with positive latex-specific IgE in
      group 2a than in those with negative latex-specific IgE (p = 0.001). The NPT was
      positive in 84.6% of group 1 and negative in all control subjects. The
      sensitivity, specificity, negative predictive value and positive predictive value
      of the latex-specific IgE assay were 90.9, 72.2, 96.3 and 50%, respectively.
      CONCLUSION: The high rate of false-positive results for latex-specific IgE by
      ImmunoCAP should be taken into account when making a diagnosis of latex allergy
      in patients with pollinosis, especially in those sensitised to more than one
      pollen species.

PMID- 22398568
TI  - Renal function in patients with HIV starting therapy with tenofovir and either
      efavirenz, lopinavir or atazanavir.
AB  - BACKGROUND: Tenofovir is associated with reduced renal function, but it is not
      clear whether there is a greater decline in renal function when tenofovir is co
      administered with a boosted protease inhibitor rather than with a nonnucleoside
      reverse transcriptase inhibitor (NNRTI). METHODS: We calculated the estimated
      glomerular filtration rate (eGFR) for patients in the Swiss HIV Cohort Study. We
      estimated the difference in eGFR over time between first therapies containing
      tenofovir and either the NNRTI efavirenz or the protease inhibitors lopinavir
      (LPV/r) or atazanavir (ATV/r), both boosted with ritonavir. RESULTS: Patients on
      a first therapy of tenofovir co-administered with efavirenz (n  = 484), LPV/r (n
      = 269) and ATV/r (n =  187) were followed for a median of 1.7, 1.2 and 1.3 years,
      respectively. Relative to tenofovir and efavirenz, the estimated difference in
      eGFR for tenofovir and LPV/r was -2.6 ml/min per 1.73 m [95% confidence interval
      (CI) -7.3 to 2.2) during the first 6 months of therapy, then followed by a
      difference of 0.0 ml/min per 1.73 m (95% CI -1.1 to 1.1) for each additional 6
      months of therapy. Relative to tenofovir and efavirenz, the estimated difference
      in eGFR for tenofovir and ATV/r was -7.6 ml/min per 1.73 m (95% CI -11.8 to -3.4)
      during the first 6 months of therapy, then followed by a difference of -0.5
      ml/min per 1.73 m (95% CI -1.6 to 0.7) for each additional 6 months of therapy.
      CONCLUSION: Tenofovir with either boosted protease inhibitor leads to a greater
      initial decline in eGFR than tenofovir with efavirenz; this decline may be worse
      with ATV/r than with LPV/r.

PMID- 22398570
TI  - Another STI associated with HIV-1 acquisition:  now what?

PMID- 22398569
TI  - Projecting the clinical benefits and risks of using efavirenz-containing
      antiretroviral therapy regimens in women of childbearing age.
AB  - OBJECTIVES: To project the outcomes of using either efavirenz or nevirapine as
      part of initial antiretroviral therapy (ART) in women of childbearing age in Cote
      d'Ivoire. METHODS: We used an HIV computer simulation model to project both the
      mother's survival and the birth defects at 10 years for a cohort of women who
      started ART with either efavirenz or nevirapine. The primary outcome was the
      ratio at 10 years of the difference in the number of women alive to the
      difference in the cumulative number of birth defects in women who started ART
      with efavirenz compared with nevirapine. In the base case analysis, the birth
      defect rate was 2.9% on efavirenz and 2.7% on nevirapine. In sensitivity
      analyses, we varied all inputs across confidence intervals reported in the
      literature. RESULTS: In the base case analysis, for a cohort of 100 000 women,
      the additional number of women alive initiating ART with efavirenz at 10 years
      was 15 times the additional number of birth defects (women alive: nevirapine 67
      969, efavirenz 68 880, difference =  911; birth defects: nevirapine 1128,
      efavirenz 1187, difference = 59). In sensitivity analysis, the teratogenicity
      rate with efavirenz had to be 6.3%, or 2.3 times higher than the rate with
      nevirapine, for the excess number of birth defects to outweigh the additional
      number of women alive at 10 years. CONCLUSION: In Cote d'Ivoire, initiating ART
      with efavirenz instead of nevirapine is likely to substantially increase the
      number of women alive at 10 years with a smaller potential number of birth
      defects.

PMID- 22398571
TI  - Safety and effectiveness of efavirenz versus nevirapine-based regimens in
      resource-limited settings:  evidence, clinical practice and modelling
      projections.

PMID- 22398572
TI  - Hemodiafiltration with online regeneration of ultrafiltrate for severe nevirapine
      intoxication in a HIV-infected patient.

PMID- 22398574
TI  - Falling through the cracks:  the gaps between depression prevalence, diagnosis,
      treatment, and response in HIV care.

PMID- 22398573
TI  - Super-infection with genotype 4 hepatitis C virus in a patient treated for
      genotype 3 acute hepatitis C.

PMID- 22398575
TI  - Collagen VI encodes antimicrobial activity: novel innate host defense properties
      of the extracellular matrix.
AB  - Collagen type VI is a subepithelial extracellular matrix component in airways and
      an adhesive substrate for oral pathogens [Bober et al.: J Innate Immun 2010;2:160
      166]. Here, we report that collagen VI displays a dose-dependent antimicrobial
      activity against group A, C, and G streptococci by membrane disruption in
      physiological conditions. The data disclose previously unrecognized aspects of
      the extracellular matrix in innate host defense.

PMID- 22398576
TI  - Stereotactic placement of ventricular catheters: does it affect proximal
      malfunction rates?
AB  - BACKGROUND: The majority of ventriculoperitoneal (VP) shunt malfunctions are due
      to proximal catheter failure. Ideal placement of Ommaya reservoirs is desired to
      avoid toxicity from intraparenchymal chemotherapy infusion. OBJECTIVE: To
      determine whether stereotactic placement of ventricular catheters decreases the
      rate of Ommaya reservoir complications and the rate of proximal VP shunt failure.
      METHODS: Under institutional review board approval, a review of a prospectively
      collected database was done identifying all patients who underwent stereotactic
      guided placement of VP shunts and Ommaya reservoirs performed by a single surgeon
      between November 2007 and November 2009. Neuronavigation was used to preset a
      surgical plan consisting of an ideal entry point (usually frontal) and target
      point (ipsilateral foramen of Monro). The navigation probe was passed along this
      trajectory. After removal of the navigation probe, pre-sized ventricular
      catheters were passed without a stylet along the created path. Post-operative CT
      scans and clinical follow-up were assessed. RESULTS: 70 patients (mean age 44.6
      years) underwent 52 VP shunt and 18 Ommaya reservoir placement procedures. Rigid
      cranial fixation was used in all cases. All catheters were placed in a single
      pass. Mean operative time was 62 min. Mean follow-up was 16.3 months. No proximal
      malfunctions or Ommaya complications have been seen thus far. One patient
      required repositioning of an Ommaya reservoir as post-operative CT showed poor
      placement (1.4%). One patient with hydrocephalus due to cryptococcal meningitis
      developed an abdominal abscess and required removal of his entire shunt with
      subsequent replacement. One patient was noted to have a small amount of
      intraventricular hemorrhage; this did not result in any clinical change and did
      not require any further intervention. No other surgical complications were noted.
      CONCLUSION: In terms of results corroborating decreased proximal malfunction
      rates, we present the largest series of stereotactic-guided ventricular catheter
      placements to date. Though time in the operating room is increased due to
      navigation registration, actual operative time is comparable to procedures
      without navigation. A longer-term follow-up is needed to assess the longevity of
      our positive short-term results.

PMID- 22398578
TI  - Diffusion of protein through the human cornea.
AB  - AIMS: To determine the rate of diffusion of myoglobin and bovine serum albumin
      (BSA) through the human cornea. These small proteins have hydrodynamic diameters
      of approximately 4.4 and 7.2 nm, and molecular weights of 16.7 and 66 kDa, for
      myoglobin and BSA, respectively. METHODS: Diffusion coefficients were measured
      using a diffusion chamber where the protein of interest and balanced salt
      solution were in different chambers separated by an ex vivo human cornea. Protein
      concentrations in the balanced salt solution chamber were measured over time.
      Diffusion coefficients were calculated using equations derived from Fick's law
      and conservation of mass in a closed system. RESULTS: Our experiments demonstrate
      that the diffusion coefficient of myoglobin is 5.5 +/- 0.9 * 10(-8) cm(2)/s (n =
      8; SD = 1.3 * 10(-8) cm(2)/s; 95% CI: 4.6 * 10(-8) to 6.4 * 10(-8) cm(2)/s) and
      the diffusion coefficient of BSA is 3.1 +/- 1.0 * 10(-8) cm(2)/s (n = 8; SD = 1.4
      * 10(-8) cm(2)/s; 95% CI: 2.1 * 10(-8) to 4.1 * 10(-8) cm(2)/s). CONCLUSIONS: Our
      study suggests that molecules as large as 7.2 nm may be able to passively diffuse
      through the human cornea. With applications in pharmacotherapy and the
      development of an artificial cornea, further experiments are warranted to fully
      understand the limits of human corneal diffusion and its clinical relevance.

PMID- 22398579
TI  - Non-covalently functionalized graphene for the potentiometric sensing of zinc
      ions.
AB  - The possibility of the application of non-covalently functionalized graphene as a
      sensing membrane for the potentiometric determination of zinc ions was examined.
      A graphene carboxylic derivative was functionalized with 1-(2-pyridylazo)-2
      naphthol, the Zn(2+) ions complexing ligand, simply by adsorption of ligand
      molecules due to pi-pi interactions. This approach has resulted in a
      potentiometric sensor characterized with significant selectivity for Zn(2+) ions
      present in solution.

PMID- 22398580
TI  - A facile synthesis and photoluminescence properties of water-dispersible Re3+
      doped CeF3 nanocrystals and solid nanocomposites with polymers.
AB  - Water-dispersible Re(3+) doped CeF(3) colloidal nanocrystals with well
      controllable morphology and high crystallinity have been successfully synthesized
      through a solvothermal process. The TEM images illustrate that the Re(3+) doped
      CeF(3) nanocrystals are rectangular (or cubic) with a mean diameter of ~10 nm.
      The excellent dispersibility in some of the polar solvents including water is
      achieved by using polyethyleneimine as the capping agent. The amine groups of the
      polymer chains on one hand bind to the nanocrystal surface; on the other hand the
      free ones could link to functional materials including bio-molecules. The CeF(3)
      nanocrystals doped with Tb(3+) and Dy(3+) ions show the characteristic emission
      of Tb(3+ 5)D(4)-(7)F(J) (J = 6-3, with (5)D(4)-(7)F(5) green emission at 542 nm
      as the strongest one) and Dy(3+ 4)F(9/2)-(6)H(15/2) (blue-green color at 478 nm)
      and (4)F(9/2)-(6)H(13/2) (yellow color at 571 nm) transitions, respectively. The
      energy transfer from Ce(3+) to Tb(3+) and Dy(3+) was also investigated in detail.
      In vitro studies of Re(3+) doped CeF(3) colloidal nanocrystals on HepG2 cells
      confirm their excellent biological compatibility. The obtained solid CeF(3) :
      Tb(3+)/PDMS nanocomposites are very stable and flexible and exhibit strong green
      photoluminescence upon UV excitation.

PMID- 22398581
TI  - Kinetics studies of rapid strain-promoted [3 + 2]-cycloadditions of nitrones with
      biaryl-aza-cyclooctynone.
AB  - Strain-promoted cycloadditions of cyclic nitrones with biaryl-aza-cyclooctynone
      (BARAC) proceed with rate constants up to 47.3 M(-1) s(-1), this corresponds to a
      47-fold rate enhancement relative to reaction of BARAC with benzyl azide and a 14
      fold enhancement over previously reported strain promoted alkyne-nitrone
      cycloadditions (SPANC). Studies of the SPANC reaction using the linear free
      energy relationship defined by the Hammett equation demonstrated that the
      cycloaddition reaction has a rho value of 0.25 +/- 0.04, indicating that reaction
      is not sensitive to substituents and thus should have broad applicability.

PMID- 22398582
TI  - Perceived eye region and the processing of fearful expressions in mild cognitive
      impairment patients.
AB  - BACKGROUND: The aim of the present study was to assess the possibility of
      compensating early facial expression recognition impairments in amnestic Mild
      Cognitive Impairment (a-MCI) patients. METHODS: Twelve patients with a-MCI and 17
      healthy participants matched according to age and education participated in the
      study. The originality of the present study was to cue the recognition of facial
      expressions (happiness, anger, fear, and neutral) by comparing eye region
      expressions and entire facial expressions. RESULTS: A deficit in the recognition
      of fearful expressions was observed in a-MCI patients relative to the control
      group, whereas recognition of all the other emotional expressions was spared.
      Nevertheless, when eye expressions cued the recognition of fearful facial
      expressions, the performance of normal controls and a-MCI patients was
      comparable. CONCLUSION: The present paper indicates a selective impairment in
      fear recognition in the prodromal state of Alzheimer's disease, and the
      possibility of compensating this deficit by orienting selective attention on
      specific facial features.

PMID- 22398583
TI  - Investigating tomographic reconstruction with a priori geometrical information.
AB  - A novel strategy to perform tomographic image reconstruction is presented, based
      on the integration of a priori information about the target image. Such
      information may come from a different imaging tool or a synthetic model. For a
      given image quality, providing a priori image information reduces the amount of
      image information to be reconstructed. According to the data processing
      inequality this requires less input data or physical measurements, therefore
      reducing exposure to ionising radiation. A prototype algorithm is described,
      consisting of a penalized ART where some a priori edge information is encoded in
      an inhomogeneous, anisotropic smoothing kernel. The algorithm is tested on a 2
      dimensional set-up based on the Shepp-Logan phantom.

PMID- 22398584
TI  - Noncontrast multidetector-row computed tomography scanning for detection of
      radiolucent calculi in acute renal insufficiency caused by bilateral ureteral
      obstruction of ceftriaxone crystals.
AB  - Noncontrast computed tomography (CT) has great advantage with higher sensitivity
      and more clear modalities in detecting urinary tract radiolucent calculi in
      patients with acute renal insufficiency (ARI) compared to other image diagnosis
      approaches. We report two cases (female, 28 years old; male, 39 years old) with
      persistent flank pain and acute anuria after the administration of ceftriaxone
      (4.0 g daily) for 2 days intravenously. No abnormality was found in the kidney
      ureter- bladder (KUB) areas with plain abdomen X-rays. A diagnosis of bilateral
      hydronephrosis was made by ultrasound examination in both cases. Serum creatinine
      levels reached up to 257 and 810 MU mol/L (normal serum creatinine level is 40
      130 MU mol/L), respectively. Vague density spots were noticed in the pelvis with
      noncontrast multidetector-row CT (MDCT) scanning. However, distinguishable
      clusters of high-density shadows were seen in pelvic areas with maximum intensity
      projections (MIP, CT values in 30-128 HU). Ceftriaxone crystal calculi were found
      on both sides of distal ureters under endoscopy. Renal function recovered in both
      patients after double-J ureteral stents were installed. Out results demonstrated
      that noncontrast MDCT scanning and MIP reconstruction as an effective diagnostic
      tool could provide clear images in detection of radiolucent calculi in urinary
      tract when conventional X-rays image are not suitable in the patients with
      obstructive anuria and ARI of unknown origin.

PMID- 22398585
TI  - A phantom-based calibration method for digital x-ray tomosynthesis.
AB  - OBJECTIVE: The purpose of this study was to develop a phantom-based experimental
      calibration method to minimize the reconstruction artifacts for the geometric
      misalignments of the digital tomosynthesis prototype. METHODS: A calibration
      phantom with ten fiducial markers was designed. Using this calibration phantom,
      the projection matrices of an experimental digital tomosynthesis prototype were
      acquired from each projection view under a series of misalignment conditions. The
      American College of Radiology mammography phantom was imaged and reconstructed
      with and without using the correction of the corresponding calibration projection
      matrices. The effectiveness of the calibration technique was then quantitatively
      analyzed through comparison of the calibrated and uncalibrated images. RESULTS:
      As the isocenter horizontal-shift increases, the reconstruction artifacts become
      clearly distinguishable. Using the calibration technique, the reconstruction
      artifacts resulting from the isocenter horizontal-shift were effectively
      minimized for the prototype. CONCLUSIONS: For the specific experimental
      conditions utilized in this study, the phantom-based calibration method
      effectively reduced reconstruction artifacts for the prototype investigated in
      this study. The calibration method holds potential to benefit other tomosynthesis
      applications.

PMID- 22398586
TI  - Mapping of bioluminescent images onto CT volume surface for dual-modality BLT and
      CT imaging.
AB  - We present a method for mapping the two-dimensional (2D) bioluminescent images
      (BLIs) onto a three-dimensional (3D) body surface derived from the computed
      tomography (CT) volume data. This mapping includes two closely-related steps, the
      spatial registration of the 2D BLIs into the coordinate system of the CT volume
      data and the light flux recovering on the body surface from BLIs. By labeling
      markers on the body surface, we proposed an effective registration method to
      achieve the spatial position alignment. The subsequent light flux recovering is
      presented based on the inverse process of the free-space light transport model
      and taking the influence of the camera lens diaphragm into account. Incorporating
      the mapping procedure into the bioluminescence tomography (BLT) reconstruction,
      we developed a dual-modality BLT and CT imaging framework to provide both optical
      and anatomical information. The accuracy of the registration and the light flux
      recovering methods were evaluated via physical phantom experiments. The
      registration method was found to have a mean error of 0.41 mm and 0.35 mm in
      horizontal and vertical direction, and the accuracy of the light flux recovering
      method was below 5%. Furthermore, we evaluated the performance of the dual
      modality BLT/CT imaging framework using a mouse phantom. Preliminary results
      revealed the potential and feasibility of the dual-modality imaging framework.

PMID- 22398587
TI  - The mathematical equivalence of consistency conditions in the divergent-beam
      computed tomography.
AB  - In this paper, we discuss the mathematical equivalence among four consistency
      conditions in the divergent-beam computed tomography (CT). The first is the
      consistency condition derived by Levine et al. by degenerating the John's
      equation; the second is the integral invariant derived by Wei et al. using the
      symmetric group theory; the third is the so-called parallel-fan-beam Hilbert
      projection equality derived by Hamaker et al.; and the fourth is the fan-beam
      data consistency condition (FDCC) derived by Chen et al. using the complex
      analysis theory. Historically, most of these consistency conditions were derived
      by their corresponding authors using complicated mathematical strategies, which
      are usually not easy to be precisely understood by researchers with only a
      general engineering mathematical background. In this paper, we symmetrically re
      derive all these consistency conditions using a friendly mathematical language.
      Based on theoretical derivation, it has been found that all these consistency
      conditions can be viewed as a necessary condition for the specific solution to
      John's equation. From the physical point of view, all these consistency
      conditions have been essentially expressed as a similar constraint on the
      projection data acquired with arbitrary two x-ray source points. Numerical
      simulations have been carried out to experimentally evaluate and verify their
      merits.

PMID- 22398588
TI  - Fast reconstruction of flat region in a super-short scan based on MD-FBP
      algorithm.
AB  - In circular cone-beam computed tomography (CT), although the minimum data
      filtered-backprojection (MD-FBP) algorithm has many significant applications,
      such as handling super-short scan problem, its reconstruction efficiency is
      limited by the heavy calculation of backprojection. In this paper, aiming at the
      image reconstruction of flat region in a super-short scan, an improved method
      based on MD-FBP algorithm is developed using an integral operation with fixed
      integral interval during the implementation of backprojection, which has an
      improvement in reconstruction efficiency and parallel performance compared with
      the original MD-FBP algorithm. It is found that if the thickness of the flat
      region is less than 0.0349 R (R is the scanning radius), the uncertainty of the
      method can be ignored. When the thickness of reconstructed region is a little
      fat, it can also be reconstructed by increasing the scanning radius befittingly.
      The results of numerical simulation and real data experiments have demonstrated
      the correctness and merits of the proposed method.

PMID- 22398589
TI  - Angular dependence of L x-ray production cross sections for Pt and Au elements in
      an external magnetic field.
AB  - The effect of the external magnetic field has been investigated on the Ll,
      Lalpha, Lbeta and Lgamma production cross sections of Pt and Au elements in the
      angular range 90 degrees -150 degrees  by using an energy dispersive x-ray
      fluorescence spectrometer. The samples were irradiated by using the gamma rays of
      59.537 keV emitted from an <formula>^{241}</formula>Am radioisotope source of 100
      mCi. The external magnetic fields have been applied two opposite directions and
      the magnitude of the external magnetic field has been fixed at +0.75 T and -0.75
      T. For B=0, Ll and Lalpha groups in the L x-ray lines are found to be spatially
      anisotropic, while those in the Lbeta and Lgamma peaks are isotropic. An
      enhancement in the differential Ll and Lalpha production cross sections is
      observed in the presence of external magnetic field. Integral cross sections for
      production of Ll, Lalpha, Lbeta and Lgamma x-rays were also deduced and were
      found to be in good agreement with the theoretical values for B=0.

PMID- 22398590
TI  - A CT-analogous scheme for time-domain diffuse fluorescence tomography.
AB  - A fiber-based non-contact scheme of the time-domain diffuse fluorescence yield
      and lifetime tomography is described that combines the time-correlated single
      photon counting technique for high-sensitive, time-resolved detection and CT
      analogous configuration for large data-set collection. A pilot validation of the
      methodology is performed for two-dimensional scenarios using simulated and
      experimental data. The results demonstrated the efficacy of the proposed scheme
      in improving the image quality.

PMID- 22398591
TI  - Enhancement of breast calcification visualization and detection using a modified
      PG method in Cone Beam Breast CT.
AB  - Cone Beam Breast CT is a promising diagnostic modality in breast imaging. Its
      isotropic 3D spatial resolution enhances the characterization of micro
      calcifications in breasts that might not be easily distinguishable in
      mammography. However, due to dose level considerations, it is beneficial to
      further enhance the visualization of calcifications in Cone Beam Breast CT images
      that might be masked by noise. In this work, the Papoulis-Gerchberg method was
      modified and implemented in Cone Beam Breast CT images to improve the
      visualization and detectability of calcifications. First, the PG method was
      modified and applied to the projections acquired during the scanning process; its
      effects on the reconstructed images were analyzed by measuring the Modulation
      Transfer Function and the Noise Power Spectrum. Second, Cone Beam Breast CT
      images acquired at different dose levels were pre-processed using this technique
      to enhance the visualization of calcification. Finally, a computer-aided
      diagnostic algorithm was utilized to evaluate the efficacy of this method to
      improve calcification detectability. The results demonstrated that this technique
      can effectively improve image quality by improving the Modulation Transfer
      Function with a minor increase in noise level. Consequently, the visualization
      and detectability of calcifications were improved in Cone Beam Breast CT images.
      This technique was also proved to be useful in reducing the x-ray dose without
      degrading visualization and detectability of calcifications.

PMID- 22398592
TI  - Percutaneous ultrasound-guided radiofrequency ablation treatment and genetic
      testing for renal cell carcinoma with Von Hippel-Lindau disease.
AB  - Percutaneous ultrasound-guided radiofrequency ablation is increasingly being
      studied in the treatment of renal tumors. Because percutaneous ultrasound-guided
      radiofrequency ablation is a minimally invasive and nephron-sparing procedure, it
      is ideally suited for patients with a single kidney, multiple tumors, or
      contraindications to conventional surgery. We report on a patient with Von Hippel
      Lindau (VHL) disease who had multicentric tumors in the single kidney that was
      successfully treated with percutaneous ultrasound-guided radiofrequncy ablation.
      The one-year follow-up showed that there was no local recurrence or metastasis.
      And genetic testing showed the patient had a T to G heterozygotic missense
      mutation at nucleotide 515 of VHL gene exon 1.

PMID- 22398593
TI  - Agnostic about agriculture.

PMID- 22398594
TI  - Another nail in the biosimilar coffin?

PMID- 22398595
TI  - Companies in rapid pursuit of Btk immunokinase.

PMID- 22398597
TI  - Cystic fibrosis drug Vertex's latest triumph.

PMID- 22398601
TI  - Hedgehog hopes lifted by approval... and stung by failure.

PMID- 22398603
TI  - HIV neutralizing antibodies reignite interest in vaccine.

PMID- 22398606
TI  - Mission therapeutics.

PMID- 22398607
TI  - Existing agbiotech traits continue global march.

PMID- 22398608
TI  - Confronting the Gordian knot.

PMID- 22398609
TI  - Agbiotech 2.0.

PMID- 22398610
TI  - Tiptoeing around transgenics.

PMID- 22398611
TI  - Know before you go.

PMID- 22398612
TI  - The Chromosome-Centric Human Proteome Project for cataloging proteins encoded in
      the genome.

PMID- 22398613
TI  - BLUEPRINT to decode the epigenetic signature written in blood.

PMID- 22398614
TI  - Detecting and annotating genetic variations using the HugeSeq pipeline.

PMID- 22398615
TI  - Update on the first cloned goats.

PMID- 22398616
TI  - Deployment of new biotechnologies in plant breeding.

PMID- 22398617
TI  - Debunking the myth that whole-genome sequencing infringes thousands of gene
      patents.

PMID- 22398619
TI  - A closer look at RNA editing.

PMID- 22398620
TI  - Tracing the genesis of human embryonic stem cells.

PMID- 22398621
TI  - Profiling PARP inhibitors.

PMID- 22398627
TI  - Pay increases for executives at private life sciences companies hit a 12-year
      low.

PMID- 22398630
TI  - Ethical challenges with deactivation of durable mechanical circulatory support at
      the end of life: left ventricular assist devices and total artificial hearts.
AB  - Left ventricular assist devices (LVADs) and total artificial hearts (TAHs) are
      surgically implanted as permanent treatment of unrecoverable heart failure. Both
      LVADs and TAHs are durable mechanical circulatory support (MCS) devices that can
      prolong patient survival but also alter end-of-life trajectory. The
      permissibility of discontinuing assisted circulation is controversial because
      device deactivation is a life-ending intervention. Durable MCS is intended to
      successfully replace native physiological functions in heart disease. We posit
      that the presence of new lethal pathophysiology (ie, a self-perpetuating cascade
      of abnormal physiological processes causing death) is a central element in
      evaluating the permissibility of deactivating an LVAD or a TAH. Consensual
      discontinuation of durable MCS is equivalent with allowing natural death when
      there is an onset of new lethal pathophysiology that is unrelated to the
      physiological functions replaced by an LVAD or a TAH. Examples of such lethal
      conditions include irreversible coma, circulatory shock, overwhelming infections,
      multiple organ failure, refractory hypoxia, or catastrophic device failure. In
      all other situations, deactivating the LVAD/TAH is itself the lethal
      pathophysiology and the proximate cause of death. We postulate that the onset of
      new lethal pathophysiology is the determinant factor in judging the
      permissibility of the life-ending discontinuation of a durable MCS. 

PMID- 22398632
TI  - Factors associated with the stages of change for dog walking among Japanese dog
      owners.
AB  - BACKGROUND: There are no previous data on factors at multiple levels associated
      with the stages of change for dog walking. The current study examined
      psychosocial and environmental correlates of the stages of change for dog walking
      among Japanese dog owners. METHODS: Dog owners (N = 1940) completed a self
      administered questionnaire that included items about demographics as well as
      psychosocial (dog attachment, dog obligation, normative belief, social norm,
      social support, self-efficacy) and environmental (access to areas, neighborhood
      safety, enjoyable scenery, frequently observing others dog walking, area where
      dogs are allowed to be off the lead) factors. MANOVA and discriminant functional
      analysis were used. RESULTS: The distribution of the dog owners across the stages
      was as follows: precontemplation (14.7%), contemplation (7.6%), preparation
      (39.7%), action (2.8%), and maintenance (35.2%). Although differences among the
      stages were found for all factors in MANOVA, the pattern of distinction among
      stages differed depending on the factors. Dog obligation and self-efficacy were
      the best predictors of the stages of change for dog walking. CONCLUSIONS:
      Although psychosocial and environmental correlates differed with the stages,
      psychosocial factors such as the sense of obligation and self-efficacy in dog
      walking seem to make relatively stronger contributions to distinctions among the
      stages.

PMID- 22398631
TI  - Atopy is inversely related to schistosome infection intensity: a comparative
      study in Zimbabwean villages with distinct levels of Schistosoma haematobium
      infection.
AB  - BACKGROUND: The hygiene hypothesis suggests that parasitic infections protect
      against allergic diseases by modulating the host's immune responses. Experimental
      studies indicate that this protection depends on the intensity of parasitic
      infection, but this observation has not been tested in human populations. The aim
      of this study is to investigate whether the intensity of Schistosoma haematobium
      infection is related to atopic responses and whether this relationship differs
      between populations with distinct parasite transmission dynamics. METHODS: The
      study was conducted in two villages with different Schistosoma haematobium
      transmission dynamics, i.e. high (n = 365) and low (n = 307) transmission.
      Allergic reactivity to the common house dust mite (Dermatophagoides
      pteronyssinus) was measured by skin prick tests and allergen-specific IgE and
      IgG4 quantified by enzyme-linked immunosorbent assay. Atopic responses were
      related to current infection intensity and schistosome transmission levels.
      RESULTS: Schistosome infection intensity was negatively associated with the skin
      prick reactivity, mite-specific IgE and the ratio IgE/IgG4 in the high
      transmission village. However, when only low levels of infection were analyzed in
      the 2 villages, there was no correlation between mite-specific responses and
      infection intensity. CONCLUSION: The relationship between schistosome infection
      and atopic responses is dependent on the intensity of current schistosome
      infection. Thus, consistent with results from animal models, with an increasing
      parasite burden, the immunoregulation of immune responses to allergens appears to
      become more pronounced.

PMID- 22398633
TI  - Highlights in lymphoma from the 2011 American Society of Hematology (ASH) Annual
      Meeting.

PMID- 22398634
TI  - MicroRNAs in vascular biology--metabolism and atherosclerosis.

PMID- 22398635
TI  - Complete transposition of great arteries with cor triatriatum: an unusual
      coexistence.
AB  - The combination of complete transposition of the great arteries and cor
      triatriatum is extremely rare. We report three infants with this rare combination
      and discuss the anatomic details apparently unique to the combined lesion.

PMID- 22398636
TI  - An unusual case of incomplete Kawasaki disease in an adolescent returning from
      holiday in Montana.
AB  - Here we present an unusual case of incomplete Kawasaki disease in a 15-year-old
      boy returning from a holiday with his family in Montana. His symptoms were
      initial diarrhoea and lethargy, with fever, rash, conjunctivitis, and arthralgia
      developing during the course of his illness. His condition worsened while he was
      at his local hospital, and he was transferred to the regional tertiary paediatric
      hospital. An initial echocardiogram was normal; however, repeat echocardiogram
      showed dilated coronary arteries with subsequent development of peeling of the
      skin on the hands and feet. The patient was started on intravenous immunoglobulin
      and high-dose aspirin and improved clinically. He was discharged home and remains
      under follow-up by the infectious diseases and cardiology teams.

PMID- 22398637
TI  - A fetus with hypoplastic left heart syndrome and tricuspid stenosis with evolving
      hydrops fetalis.
AB  - Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect that
      results in death if not treated shortly after birth. In approximately 60 to 70%
      of cases, HLHS can be detected prenatally and generally is well tolerated due to
      the presence of the foramen ovale and ductus arteriosus, which allow for blood to
      bypass the left side of the heart but still provide adequate blood flow to the
      systemic circulation. A rare case of HLHS involving a fetus with tricuspid valve
      stenosis, abnormal venous Doppler findings, and hydrops is reported.

PMID- 22398638
TI  - Vise location of the vertical vein in a neonate with a supracardiac total
      anomalous pulmonary venous connection.

PMID- 22398640
TI  - Ribosomal RNA of Hyacinthus orientalis L. female gametophyte cells before and
      after fertilization.
AB  - The nucleolar activity of Hyacinthus orientalis L. embryo sac cells was
      investigated. The distributions of nascent pre-rRNA (ITS1), 26S rRNA and of the
      5S rRNA and U3 snoRNA were determined using fluorescence in situ hybridization
      (FISH). Our results indicated the different rRNA metabolism of the H. orientalis
      female gametophyte cells before and after fertilization. In the target cells for
      the male gamete, i.e., the egg cell and the central cell whose activity is
      silenced in the mature embryo sac (Piecinski et al. in Sex Plant Reprod 21:247
      257, 2008; Niedojadlo et al. in Planta doi: 10.1007/s00425-012-1599-9 , 2011),
      rRNA metabolism is directed at the accumulation of rRNPs in the cytoplasm and
      immature transcripts in the nucleolus. In both cells, fertilization initiates the
      maturation of the maternal pre-rRNA and the expression of zygotic rDNA. The
      resumption of rRNA transcription observed in the hyacinth zygote indicates that
      in plants, there is a different mechanism for the regulation of RNA Pol I
      activity than in animals. In synergids and antipodal cells, which have somatic
      functions, the nucleolar activity is correlated with the metabolic activity of
      these cells and changes in successive stages of embryo sac development.

PMID- 22398639
TI  - Role of acylamino acid-releasing enzyme/oxidized protein hydrolase in sustaining
      homeostasis of the cytoplasmic antioxidative system.
AB  - Acylamino acid-releasing enzyme/oxidized protein hydrolase (AARE/OPH) has been
      biochemically demonstrated to be a bifunctional protease that has exopeptidase
      activity against Nalpha-acylated peptides and endopeptidase activity against
      oxidized and glycated proteins; however, its physiological role remains unknown.
      In this study, to determine its physiological significance, we produced AARE/OPH
      overexpressing and -suppressed plants and assessed the biological impacts of
      AARE/OPH. The subcellular localization of Arabidopsis AARE/OPH was found to be
      cytoplasmic and nuclear by transient expression analysis of tdTomato-fused
      Arabidopsis AARE/OPH. Overexpression of AARE/OPH exhibited no apparent effect on
      the level of oxidized proteins because wild types probably have inherently high
      AARE/OPH activity. Through RNAi gene suppressing, we successfully produced
      AARE/OPH-suppressed Arabidopsis plants (aare) that exhibited almost no AARE
      activity. In the aare plant, electrolyte leakage by methyl viologen treatment was
      enhanced compared to that of non-transformant plants, suggesting that the plasma
      membranes of aare easily suffered oxidative damage, probably as a result of
      deterioration of the cytoplasmic antioxidative system. Correspondingly, proteomic
      analysis revealed that the aare plant accumulated a number of oxidized proteins
      including cytoplasmic antioxidant enzymes. On the basis of these results, we
      concluded that AARE/OPH plays a homeostatic role in sustaining the cytoplasmic
      antioxidative system.

PMID- 22398641
TI  - Publication rate of abstracts presented at the Annual Congress of the Spine
      Society of Europe (years 2000-2003).
AB  - INTRODUCTION: The quality of presentations at medical conferences is of major
      importance. The publication rate (PR) following congress presentation is an
      indicator of the extent and quality of a scientific society's activity. The
      purpose of this study was to investigate publication rates in the Spine Society
      of Europe (SSE), compare them with the results for American spine societies, and
      determine factors affecting publication. MATERIALS AND METHODS: All 839 abstracts
      of podium and poster presentations at SSE congresses held in 2000-2003 were
      investigated. PRs in peer-reviewed journals within a period of 5 years were
      assessed. Subgroup analyses were performed for different study types. The
      consistency of abstracts with publications was also analyzed. RESULTS: The
      overall PR was 37.8%, with a mean of 17.7 +/- 15.7 months between congress and
      publication and a mean impact factor of 1.8 +/- 1.0 at the time of publication.
      Comparatively high PRs were found for podium presentations versus posters,
      studies with higher versus lower levels of evidence, experimental versus clinical
      studies, prospective versus retrospective studies, randomized versus
      nonrandomized studies, studies reporting significant main results versus those
      without, and multicenter studies versus single-center studies. Biomechanical
      studies also achieved high PRs. CONCLUSION: The PR was similar to that of NASS
      (40%) and only slightly inferior to that of SRS (47%) and ISSLS (45%). This shows
      the high quality of presentations at SSE congresses. The fate of unpublished
      abstracts is worth further consideration. It is questionable whether it is
      acceptable to cite abstracts that have not passed a journal's peer-review process
      and to implement their results in clinical practice.

PMID- 22398643
TI  - De novo deletion of 1q31.1-q32.1 in a patient with developmental delay and
      behavioral disorders.
AB  - We describe the case of a 6-year-old boy with a de novo deletion of the long arm
      of chromosome 1 encompassing band 1q31.1-q32.1, minor facial anomalies, mild
      developmental delay, and behavioral disorders. His postnatal karyotype was
      normal. Using array-comparative genomic hybridization, we identified and
      characterized a de novo 1q interstitial deletion of about 15.6 Mb, which
      partially overlaps those of other reported cases. We considered the gene content
      of the deleted region in an attempt to compare the clinical features of our
      patient with these other cases, even though they were not characterized
      molecularly in detail. The most remarkable difference was the absence of
      microcephaly. To the best of our knowledge, this is the first report of a de novo
      1q31.1-q32.1 deletion. Moreover, it illustrates how molecular delineation
      associated with fine clinical characterization can improve the genotype-phenotype
      correlations of classical cytogenetic abnormalities.

PMID- 22398642
TI  - Endoscopic transnasal odontoid resection to decompress the bulbo-medullary
      junction: a reliable anterior minimally invasive technique without posterior
      fusion.
AB  - PURPOSE: Anterior decompression of the craniovertebral junction is reserved to
      patients with irreducible ventral bulbo-medullary lesions and rapidly
      deteriorating neurological functions. Classically performed through the transoral
      approach, the exposure of this region can be now achieved by a minimally invasive
      endonasal endoscopic approach (EEA). METHODS: Four patients with irreducible,
      anterior bulbo-medullary compression due to rheumatoid pannus and basilar
      invagination were enrolled. The imaged-guided EEA was used to resect the odontoid
      process, trying to preserve the C1 anterior arch. RESULTS: Neurological
      improvement and adequate bulbo-medullary decompression were obtained in all
      patients. In two cases, anterior C1 ring was preserved. These patients did not
      required a posterior fusion. CONCLUSIONS: Compared with the standard transoral
      technique, the EEA provides the same good exposure but with potentially less
      complications. The preservation of the anterior C1 arch can contribute to avoid
      cranial settling and posterior fusion with its related risk of subaxial
      instability.

PMID- 22398644
TI  - Long-term outcome of duplex kidney with ectopic ureter treated by antireflux
      ureterocystic reimplantation.
AB  - INTRODUCTION: We present our 35 years' experience of managing duplex kidneys with
      ectopic ureter by simple antireflux ureterocystic reimplantation. PATIENTS AND
      METHODS: From December 1974 to April 2009, 36 female children, aged 10 months to
      13 years, were treated. Hutch's antireflux ureterocystic reimplantation was
      performed after preoperative location and intraoperative identification of the
      unilateral or bilateral ectopic ureters. RESULTS: Thirty-one patients had follow
      up data (range 11 months to 25 years). Postoperatively, there were no reports of
      dribbling incontinence, urinary frequency, lumbago or recurrent fever with the
      exception of urinary incontinence in 2 patients. Cystography and intravenous
      pyelography performed in 27 cases showed no or minimal bladder-ureter reflux.
      Superior kidney hydronephrosis improved in 12 cases and showed no change in the
      remaining patients. CONCLUSIONS: Antireflux ureterocystic reimplantation is a
      simple method to treat the duplex kidney with ectopic ureter with minimal induced
      trauma.

PMID- 22398645
TI  - Variation in the recorded incidence of amputation of the lower limb in England.
AB  - AIMS/HYPOTHESIS: The study aimed to explore the variation in recorded incidence
      of lower limb amputation in England. METHODS: The incidences of amputations in
      adults with and without diabetes were determined from hospital episode statistics
      over 3 years to 31 March 2010 and compared between the 151 Primary Care Trusts
      (PCTs) in England. RESULTS: There were 34,109 amputations, including 16,693
      (48.9%) in people with diabetes. The incidence was 2.51 per 1,000 person-years in
      people with diabetes and 0.11 per 1,000 person-years in people without (relative
      diabetes risk 23.3). Incidence varied eightfold across PCTs in people both with
      diabetes (range 0.64-5.25 per 1,000 person-years) and without (0.03-0.24 per
      1,000 person-years). Amputations in people with diabetes varied tenfold--both
      major (range 0.22-2.20 per 1,000 person-years) and minor (range 0.30-3.25 per
      1,000 person-years). The incidences of minor and major amputations were
      positively correlated both in those with (r = 0.537, p < 0.0005) and without (r =
      0.611, p < 0.0005) diabetes. Incidences of amputations were also correlated
      between people with and without diabetes (total amputations r = 0.433, p <
      0.0005; major amputations r = 0.528, p < 0.0005). There was a negative
      correlation between the incidence of amputation and estimated prevalence of
      ethnic Asians. No association was found between the PCT incidence of either total
      amputations and general population prevalence of social deprivation (r = -0.138,
      p = 0.092) or smoking (r = 0.137, p = 0.096). CONCLUSIONS/INTERPRETATION:
      Variation in amputation incidence occurs across England. Because of the
      similarity in amputation variation between people with and without diabetes the
      variation may reflect generic differences in local healthcare delivery, although
      racial factors may also contribute.

PMID- 22398646
TI  - HbA1c in type 2 diabetes diagnostic criteria: addressing the right questions to
      move the field forwards.
AB  - This commentary aims to move the debate regarding the adoption of HbA(1c) for
      diagnosis of type 2 diabetes forwards by highlighting the need to avoid
      addressing irrelevant questions, in particular, comparison of individuals
      diagnosed with different diagnostic criteria. Instead, we provide a list of
      important future questions, including whether adoption of HbA(1c) as the primary
      diagnostic test improves uptake of diabetes screening, with resultant earlier
      diagnosis and improvement in outcomes.

PMID- 22398647
TI  - B-type natriuretic peptide and glycaemia: an emerging cardiometabolic pathway?
AB  - There is emerging evidence of cross-talk between the myocardium and systemic
      metabolic pathways. In particular, there is interest in the potential metabolic
      effects of A-type and B-type natriuretic peptides (ANP and BNP), produced in the
      myocardial tissue in response to ventricular stretch and cardiac overload. This
      commentary provides an overview of the evidence that natriuretic peptides promote
      lipolysis and enhance adiponectin production. In addition, we review new and
      existing evidence that BNP may directly improve glucose control, or else lower
      glucose indirectly via enhanced capillary permeability or greater renal
      excretion. Further investigation of the links between natriuretic peptide and
      glycaemia would seem important given the potential to reveal novel mechanisms to
      treat diabetes.

PMID- 22398648
TI  - Perceptions and attitudes of French general practitioners towards rapid antigen
      diagnostic tests in acute pharyngitis using a randomized case vignette study.
AB  - OBJECTIVES: This study had three objectives: (i) to assess the use of rapid
      antigen diagnostic tests (RADTs) and their impact on the antibiotic prescribing
      behaviour of general practitioners (GPs) for acute pharyngitis; (ii) to study the
      barriers to the use of RADTs; and (iii) to identify GPs' characteristics
      associated with non-compliance with French guidelines. METHODS: We conducted a
      cross-sectional survey of a representative sample of 369 self-employed GPs in
      south-eastern France using a randomized case vignette study. RESULTS: The
      availability of an RADT allowed a 44% relative reduction in the rate of
      antibiotic prescriptions. Of GPs for whom the test was available, 34% did not use
      an RADT in our acute pharyngitis vignette and 13% of those who used the test
      prescribed an antibiotic despite a negative RADT result. Non-compliance with
      French guidelines (i.e. not using an RADT and/or prescribing an antibiotic
      despite a negative RADT result) was independently associated with the following
      factors: less reading of medical journals, less benefits/risks discussion with
      patients about vaccinations and higher perception that clinical examination was
      sufficient to prescribe antibiotics. The three main declared barriers to RADT use
      were: time to perform the test, patient expectations regarding antibiotics and
      the perception that clinical examination was sufficient to decide to prescribe an
      antibiotic. CONCLUSIONS: RADTs are a useful but not sufficient tool to reduce
      antibiotic prescribing in general practice. The results of this study increase
      understanding of the factors underlying clinical decision making for acute
      pharyngitis and may contribute to the development of interventions to improve
      practice.

PMID- 22398649
TI  - An integrated surrogate model for screening of drugs against Mycobacterium
      tuberculosis.
AB  - OBJECTIVES: The intracellularly surviving and slow-growing pathogen,
      Mycobacterium tuberculosis, adapts the host cell environment for its active and
      dormant life cycle. It is evident that the lack of appropriate high-throughput
      screening of inhibitors within host cells is an impediment for the early stages
      of anti-tubercular drug discovery. We aimed to develop an integrated surrogate
      model that enhances the screening of large inhibitor libraries. METHODS:
      Different mycobacterial species were compared for their growth, drug
      susceptibility and intracellular uptake. A 6-well plate solid agar-based spot
      culture growth inhibition (SPOTi) assay was developed into a higher throughput
      format. The uptake and intracellular survival of Mycobacterium aurum within mouse
      macrophage cells (RAW 264.7) were optimized using 24/96-well plate formats.
      RESULTS: Fast-growing, non-pathogenic M. aurum was found to have an antibiotic
      susceptibility profile similar to that of M. tuberculosis. The sensitivity to an
      acidic pH environment and the ability to multiply inside RAW 264.7 macrophages
      provided additional advantages for employing M. aurum in intracellular drug
      screening methods. A selection of anti-tubercular drugs inhibited the growth and
      viability of M. aurum inside the macrophages at different levels. CONCLUSIONS: We
      present a rapid, convenient, high-throughput surrogate model, which provides a
      comprehensive evaluation platform for new chemical scaffolds against different
      physiological stages of mycobacteria within the primary cell environment of the
      host. The results using anti-tubercular drugs validate this model for screening
      libraries of existing and novel chemical entities.

PMID- 22398650
TI  - Characterization of methicillin-resistant Staphylococcus aureus displaying
      increased MICs of ceftaroline.
AB  - OBJECTIVES: To characterize the mechanisms responsible for elevated MICs of
      ceftaroline for methicillin-resistant Staphylococcus aureus (MRSA). METHODS:
      During the 2008 Assessing Worldwide Antimicrobial Resistance Evaluation ('AWARE')
      surveillance programme, four S. aureus collected from separate patients in
      Athens, Greece, demonstrated ceftaroline MICs of 4 mg/L. These isolates were
      clonally related and one strain (13101) was selected for further
      characterization. Two strains (4981 and 4977) displaying ceftaroline MICs of 1
      and 2 mg/L, respectively, were included for comparison. All strains originated
      from the same hospital. Penicillin-binding protein (PBP) affinities for
      ceftaroline and comparators were determined. Strains were typed by single-locus
      typing (i.e. spa typing), multilocus sequence typing ('MLST') and by multiple
      locus variable-number tandem repeat fingerprinting (MLVF). The presence of
      Pantone-Valentine leucocidin and the staphylococcal cassette chromosome mec types
      was assessed. We also performed nucleotide sequencing of the mecA (encoding
      PBP2a) promoter and ribosomal binding site (rbs) regions and mecR1. RESULTS:
      Ceftaroline demonstrated the highest PBP2a affinity with strain 4981 (ST5-MRSA
      II) (IC(50) 0.06 mg/L; MIC 1 mg/L). Strains 4977 and 13101 (both ST239-MRSA-III)
      showed indistinguishable MLVF profiles. Ceftaroline PBP2a binding affinity in
      strains 4977 (IC(50) 0.25 mg/L; MIC 2 mg/L) and 13101 (IC(50) 1 mg/L; MIC 4 mg/L)
      was 4- and 16-fold lower than 4981, respectively. Strain 4981 contains a wild
      type PBP2a, while strains 4977 and 13101 have N(146)K and E(150)K alterations in
      the non-penicillin-binding domain. Additionally, 13101 has one substitution
      (H(351)N) in the transpeptidase domain. Alterations in the mecR1, mecA promoter
      or rbs regions were not observed. CONCLUSIONS: Increased ceftaroline MICs were
      associated with decreased PBP2a binding affinity and reflected alterations in
      PBP2a.

PMID- 22398652
TI  - Double trouble: how big a problem is redundant anaerobic antibiotic coverage in
      Veterans Affairs medical centres?
AB  - OBJECTIVES: To assess the prevalence of, and the variation in, avoidable use of
      metronidazole in the Veterans Affairs (VA) healthcare system METHODS: Barcode
      Medication Administration (BCMA) data were retrospectively assessed for all
      patients hospitalized between January 2006 and December 2010 in acute-care wards
      of all VA medical centres (VAMCs) with complete BCMA data and at least 10 acute
      care non-intensive care unit (ICU) beds. Potentially avoidable metronidazole days
      of therapy (DOT) were defined as the administration of metronidazole with another
      anti-anaerobic antibiotic on the same day for at least two consecutive days
      during the same hospitalization. Metronidazole was not considered redundant in
      combination with another anti-anaerobic agent within 28 days after a positive
      test for Clostridium difficile and during hospitalizations associated with
      discharge diagnosis codes for cholecystitis or cholangitis. RESULTS: A total of
      128 VAMCs satisfied the inclusion criteria. Over the study period there were a
      total of 782,821 DOT of metronidazole (57.4 DOT per 1000 patient-days), of which
      183,267 (23.4%) fulfilled the criteria for avoidable metronidazole DOT. The
      percentage of avoidable metronidazole DOT remained stable over the study period
      (22.8% in 2006 and 22.9% in 2010) despite a decrease in overall metronidazole
      use. There was wide variation in the percentage of avoidable metronidazole DOT
      among facilities (2010: median 20.3%, IQR 15.3%-29.4%). Piperacillin/tazobactam
      was the most commonly administered drug on avoidable metronidazole DOT (56.8%).
      CONCLUSIONS: Potentially avoidable use of metronidazole affected about a quarter
      of all days when metronidazole was given. The combination of metronidazole with
      piperacillin/tazobactam was particularly common and represents a possible target
      for antibiotic stewardship interventions.

PMID- 22398653
TI  - Increased MICs of gamithromycin and tildipirosin in the presence of the genes
      erm(42) and msr(E)-mph(E) for bovine Pasteurella multocida and Mannheimia
      haemolytica.

PMID- 22398651
TI  - Carbapenem-resistant Gram-negative bacilli in Canada 2009-10: results from the
      Canadian Nosocomial Infection Surveillance Program (CNISP).
AB  - OBJECTIVES: To investigate the occurrence and molecular mechanisms associated
      with carbapenemases in carbapenem-resistant Gram-negative isolates from Canadian
      cases. METHODS: Twenty hospital sites across Canada submitted isolates for a 1
      year period starting 1 September 2009. All Enterobacteriaceae with MICs >= 2 mg/L
      and Acinetobacter baumannii and Pseudomonas aeruginosa with MICs >= 16 mg/L of
      carbapenems were submitted to the National Microbiology Laboratory (NML) where
      carbapenem MICs were confirmed by Etest and isolates were characterized by PCR
      for carbapenemase genes, antimicrobial susceptibilities, PFGE and plasmid
      isolation. RESULTS: A total of 444 isolates (298 P. aeruginosa, 134
      Enterobacteriaceae and 12 A. baumannii) were submitted to the NML of which 274
      (61.7%; 206 P. aeruginosa, 59 Enterobacteriaceae and 9 A. baumannii) met the
      inclusion criteria as determined by Etest. Carbapenemase genes were identified in
      30 isolates: bla(GES-5) (n = 3; P. aeruginosa), bla(KPC-3) (n = 7;
      Enterobacteriaceae), bla(NDM-1) (n = 2; Enterobacteriaceae), bla(VIM-2) and
      bla(VIM-4) (n = 8; P. aeruginosa) bla(SME-2) (n = 1; Enterobacteriaceae) and
      bla(OXA-23) (n = m9; A. baumannii). PFGE identified a cluster in each of
      Enterobacteriaceae, P. aeruginosa and A. baumannii corresponding to isolates
      harbouring carbapenemase genes. Three KPC plasmid patterns (IncN and FllA) were
      identified where indistinguishable plasmid patterns were identified in unrelated
      clinical isolates. CONCLUSIONS: Carbapenemases were rare at the time of this
      study. Dissemination of carbapenemases was due to both dominant clones and common
      plasmid backbones.

PMID- 22398654
TI  - Catalytic asymmetric synthesis of chromenes and tetrahydroquinolines via
      sequential allylic alkylation and intramolecular Heck coupling.
AB  - Highly enantioselective synthesis of chiral chromenes and tetrahydroquinolines is
      achieved by combining asymmetric copper-catalyzed allylic substitution with
      Grignard reagents and an efficient intramolecular Heck reaction. Moreover, the
      exocyclic double bond formed in the cyclisation was subjected to RCM,
      hydroboration and hydrogenation illuminating the synthetic versatility of these
      heterocycles.

PMID- 22398655
TI  - Modelling and simulation of edoxaban exposure and response relationships in
      patients with atrial fibrillation.
AB  - Edoxaban is a novel, orally available, highly specific direct inhibitor of factor
      Xa and is currently being developed for the treatment and prevention of venous
      thromboembolism and prevention of stroke and systemic embolism in patients with
      non-valvular atrial fibrillation (NVAF). The objectives of the present analyses
      were to characterise edoxaban population pharmacokinetics (PPK) and identify
      potential intrinsic and extrinsic factors affecting variability in edoxaban
      exposure, determine if there are relationships between edoxaban pharmacokinetics
      or biomarkers and the risk of bleeding in patients with NVAF using an exposure
      response model, and to use the PPK and exposure-response model to support dose
      selection for a phase III trial of edoxaban in patients with NVAF. PPK analysis
      of data from 1,281 edoxaban-dosed subjects with intrinsic factors such as renal
      impairment or NVAF and extrinsic factors such as concomitant medications revealed
      significant effects of renal impairment and concomitant strong P-glycoprotein (P
      gp) inhibitors on the pharmacokinetics of edoxaban. Exposure-response analysis
      found that in patients with NVAF, the incidence of bleeding events increased
      significantly with increasing edoxaban exposure, with steady-state minimum
      concentration (Cmin,ss) showing the strongest association. Clinical trial
      simulations of bleeding incidence were used to select 30 mg and 60 mg once-daily
      edoxaban with 50% dose reductions for patients with moderate renal impairment or
      receiving concomitant strong P-gp inhibitors as the treatment regimens in the
      ENGAGE AF-TIMI 48 (NCT00781391) trial.

PMID- 22398656
TI  - Absorption vs. redox reduction of Pd2+ and Cu2+ on triboelectrically and
      naturally charged dielectric polymers.
AB  - It has recently been reported that Teflon and polyethylene (PE) if rubbed by
      polymethylmethacrylate (PMMA) or Nylon as well as non-rubbed PMMA and Nylon
      induce "redox" reactions, including those of the reduction of Pd(+2) and Cu(+2)
      ions. On this basis, it was deduced that these dielectric materials may hold
      ?10(13)-10(14) of "hidden" electrons cm(-2), a value at least three orders of
      magnitude higher than the charge that a dielectric surface can accumulate without
      being discharged in air. The "hidden" electrons were termed "cryptoelectrons". In
      variance to these reports, we offer here an alternative interpretation. Our model
      is supported by X-ray photoelectron spectroscopy, contact angle and vibrating
      electrode (modified Kelvin probe) measurements performed on representative
      examples. Rubbing of the polymers was found to transfer polymer fragments between
      the rubbed surfaces altering their physical properties. The transferred polymer
      fragments promote adsorption of Cu(2+) and Pd(2+) ions. It was found that Teflon
      and PE rubbed with PMMA and Nylon, and non-rubbed PMMA and non-rubbed Nylon do
      not induce "redox" reactions of Cu(2+) and Pd(2+) ions but adsorb these ions on
      their surfaces. Furthermore, the earlier reported reduction of Pd(2+) to Pd(0) by
      electrons, as detected by catalytic activity of Pd(0) in a Cu-plating bath, can
      be alternatively explained by reduction of adsorbed Pd(2+) by the reducing agents
      of the bath itself. Based on these findings, we support the hypothesis that
      charging of dielectric polymers is due to ions or free radicals rather than
      electrons and there is no evidence to invoke a hypothesis of "cryptoelectrons".

PMID- 22398657
TI  - A recurring valvular vegetation.

PMID- 22398658
TI  - Two-dimensional speckle-tracking echocardiography for atrioventricular accessory
      pathways persistent ventricular pre-excitation despite successful radiofrequency
      ablation.
AB  - AIMS: The present study was undertaken to investigate the concordance between
      longitudinal two-dimensional (2D)-speckle-tracking data and endocardial mapping
      for localizing atrioventricular accessory pathways (AP), and whether longitudinal
      2D-speckle-tracking imaging accurately identifies the contractile abnormalities
      associated with AP and the effect of radiofrequency ablation. METHODS AND
      RESULTS: Echocardiograms were repeated twice in 40 patients with Wolff-Parkinson
      White (WPW) syndrome (before and early after ablation) and in 40 healthy controls
      to obtain longitudinal 2D strain and strain rate data. The site of ablation was
      considered as the gold standard for the AP localization. While control patients
      had a homogeneous strain pattern, all but two patients with WPW had an abnormal
      deformation pattern with three peaks in one or two basal contiguous segments: an
      early peak concomitantly with the delta wave followed by a systolic and a post
      sytolic one. The rapid increase in LV longitudinal deformation within the basal
      pre-excited zone resulted in a pre-systolic peak strain rate at the beginning of
      the delta wave by SR imaging that was not found in controls. The early basal
      contraction spread towards the mid-ventricle before merging with the normal
      activated segments in 15 patients (39%). Contractile abnormalities were no more
      than one adjacent segment different compared with the AP ablation site in all
      these 38 patients. Regional strain was impaired in the pre-excited areas
      especially in AP localized in the interventricular septum. The abnormal
      deformation pattern persisted in 16 (42%) patients despite successful
      radiofrequency ablation. However, the difference in the regional strain between
      WPW patients and controls did not remain after ablation. CONCLUSION: Longitudinal
      2D-speckle-tracking data accurately match with endocardial mapping findings for
      localizing AP. Longitudinal 2D-speckle-tracking imaging accurately identifies AP
      associated contractile abnormalities. Longitudinal 2D-speckle-tracking identifies
      persistence of local ventricular pre-excitation immediately after successful
      ablation.

PMID- 22398660
TI  - New treatments and treatment goals for patients with relapsing-remitting multiple
      sclerosis.
AB  - PURPOSE OF REVIEW: The aims of this article are to review emerging therapies for
      multiple sclerosis (MS) and to consider new approaches to assessment and
      achievement of treatment success in patients with this disease. RECENT FINDINGS:
      A number of disease-modifying therapies for MS, including oral agents, are in
      advanced development and likely to be available soon. Fingolimod has been
      approved recently by the US Food and Drug Administration. Agents in development
      include alemtuzumab, BG-12, daclizumab, teriflunomide, laquinimod, and B-cell
      targeted monoclonal antibodies ocrelizumab and ofatumumab. The advent of emerging
      efficacious therapies has set the stage for re-evaluation of treatment goals for
      patients with MS. Freedom from disease, defined by the absence of relapses,
      disability progression, and radiologic evidence of disease activity, is
      increasingly seen as the measure of treatment success. SUMMARY: New MS treatments
      may provide the basis for aggressive early intervention in patients with MS and
      intensification of treatment when disease is not controlled. The availability of
      therapies that can achieve higher treatment goals may significantly improve long
      term outcomes for MS patients.

PMID- 22398661
TI  - Individualizing treatment goals and interventions for people with MS.
AB  - PURPOSE OF REVIEW: The aim of this article is to consider factors that should be
      evaluated in the selection of therapy for people with multiple sclerosis (MS).
      This includes a review of current approaches to treatment selection and how to
      align this process with patients' treatment goals. These issues have increased in
      importance with the availability of new disease-modifying therapies and will
      continue to do so as more novel treatments are approved. RECENT FINDINGS: The
      model for decision making in the management of people with MS as well as other
      chronic diseases has evolved from one in which medication is prescribed by the
      neurologist and the person is expected to comply with treatment, to one in which
      the neurologist and individual with MS achieve concordance with respect to both
      the expectations and goals of therapy and the means to achieve them. This shift
      has resulted in a requirement for easily understood evidence-based information
      about the risks and benefits of different treatment alternatives. It has been
      demonstrated that providing MS sufferers with such information increases
      effective self-management and satisfaction. SUMMARY: Healthcare providers
      involved in the treatment of MS have an increased responsibility to ensure people
      with this disease, their partners, and when appropriate, their families are
      involved in all decisions regarding care. This includes helping to select and
      adjust therapy on the basis of the individual MS sufferer's characteristics and
      needs that are likely to evolve as the disease progresses.

PMID- 22398662
TI  - Treatment of relapsing-remitting multiple sclerosis:  current approaches and
      unmet needs.
AB  - PURPOSE OF REVIEW: The aim of this review is to summarize unmet needs for
      patients with multiple sclerosis (MS). It is important to understand the current
      status of these patients and both the benefits and limitations of the most
      commonly used MS treatments as new medications with the potential to simplify
      therapy and improve outcomes may soon be available. RECENT FINDINGS: Current
      treatments for MS decrease the frequency of relapses and slow progressive
      disability. However, nearly all of these medications require frequent
      administration, and some patients also experience side effects. In some patients,
      adherence to MS treatment may be less than optimal. This may be associated with
      increased risk for relapses and hospitalizations and higher cost of care.
      SUMMARY: Healthcare providers involved in the treatment of MS must be aware of
      the unmet needs of their patients and intervene as needed to improve adherence
      and/or modify treatment regimens to optimize outcomes.

PMID- 22398663
TI  - How important is the context of an adolescent's first alcoholic drink? Evidence
      that parental provision may reduce later heavy episodic drinking.
AB  - OBJECTIVE: This study examined the extent to which a retrospective measure of
      parental provision of the first alcoholic beverage was related to current heavy
      episodic drinking and current responsible drinking practices. SAMPLE: 608 14- to
      17-year-olds from the 2007 Australian National Drug Strategy Household Survey.
      MEASURES: Source of first alcoholic beverage (friends/parents/others), source of
      current alcohol, age of onset of alcohol use, current responsible drinking
      practices, and proportion of current friends who drink. RESULTS: Binary logistic
      and multiple regression procedures revealed that parental provision of an
      adolescent's first alcoholic beverage predicted lower current heavy episodic
      drinking, and responsible drinking mediated this association. DISCUSSION: The
      results suggested that for adolescents who become alcohol users, parental
      provision of the first drink may reduce subsequent alcohol-related risks compared
      to introduction to alcohol by friends and other sources. Alcohol-related risks
      remain significant for adolescents who consume alcohol, independent of who is the
      provider.

PMID- 22398664
TI  - The Influence of MDR1 G2677T/a genetic polymorphisms on the pharmacokinetics of
      repaglinide in healthy Chinese volunteers.
AB  - AIMS: The aim of this study was to evaluate the pharmacogenetic variability in
      the disposition of repaglinide in healthy Chinese subjects. METHODS: A single
      dose of 2 mg repaglinide was orally administered to 24 healthy Chinese subjects.
      The serum concentrations of repaglinide were measured by using liquid
      chromatography/tandem mass spectrometry. We determined the polymorphic alleles of
      MDR1 C1236T, MDR1 G2677T/A, MDR1 C3435T, CYP3A4*18, OATP1B1 G388A, and OATP1B1
      T521C in each subject. RESULTS: The area under the plasma concentration-time
      curve from time 0 to infinity (AUC((0-inf))) of repaglinide was significantly
      higher in subjects possessing the MDR1 2677GT and 2677TT alleles than in those
      with the MDR1 2677GG and 2677TA alleles (p = 0.007). The mean AUCs and peak
      plasma concentration were higher in subjects with the 521TC allele than in those
      with the OATP1B1 521TT allele, and the OATP1B1 388A allele is associated with a
      reduced trend of pharmacokinetic exposure; however, these trends were not
      statistically significant. The pharmacokinetics of repaglinide was not associated
      with MDR1 C1236T, MDR1 C3435T, and CYP3A4*18. CONCLUSION: This study shows that
      the genetic polymorphisms of MDR1 G2677T/A might explain the variability in the
      pharmacokinetics of repaglinide in the Chinese population.

PMID- 22398665
TI  - Coherent two-dimensional infrared spectroscopy: quantitative analysis of protein
      secondary structure in solution.
AB  - We present a method to quantitatively determine the secondary structure
      composition of globular proteins using coherent two-dimensional infrared (2DIR)
      spectroscopy of backbone amide I vibrations (1550-1720 cm(-1)). Sixteen proteins
      with known crystal structures were used to construct a library of 2DIR spectra,
      and the fraction of residues in alpha-helix, beta-sheet, and unassigned
      conformations was determined by singular value decomposition (SVD) of the
      measured two-dimensional spectra. The method was benchmarked by removing each
      individual protein from the set and comparing the composition extracted from 2DIR
      against the composition determined from the crystal structures. To highlight the
      increased structural content extracted from 2DIR spectra a similar analysis was
      also carried out using conventional infrared absorption of the proteins in the
      library.

PMID- 22398666
TI  - Apportionment of the airborne PM10 in Spain. Episodes of potential negative
      impact for human health.
AB  - The particulate matter with an aerodynamic diameter less than or equal to 10 and
      2.5 microns respectively (PM10 and PM2.5) constitutes one of the main air
      pollutants, which is currently regulated in Europe through Directive 2008/50/EC
      due to its proven harmful effects on human health. In this paper, the airborne
      PM10 samples collected in Zaragoza city during 2001-2009 were apportioned by
      statistical tools based on principal component analysis with absolute principal
      component scores (PCA-APCS). PM10 samples were characterized regarding their
      concentrations of polycyclic aromatic hydrocarbons (PAH) and water-soluble ions.
      PAH were analyzed by gas chromatography-mass spectrometry-mass spectrometry
      detection (GC-MS-MS) and ions were analyzed by ion chromatography. A total of
      five factors were identified by PCA-APCS corresponding to different anthropogenic
      and natural sources. This work was focused on analyzing in more detail those
      samples involving higher negative impact on human health, in particular, PM10
      samples exceeding the daily PM10 limit value of 50 MUg m(-3) according to
      Directive 2008/50/EC and samples with concentrations of benzo[a]pyrene (BaP)
      higher than the upper assessment threshold (BaP > 0.6 ng m(-3)) established by
      the Directive 2004/107/EC. Most of the exceedances of the daily PM10 limit value
      were associated with direct and indirect North-African long-range transport.
      During these exceedances, it was observed that anthropogenic pollution sources
      slightly decreased with regard to the natural sources. This indicated that
      episodes of high PM10 could have a natural origin associated with long-range
      transport from the African continent. On the contrary, those exceedances with
      regional contribution and samples with BaP concentrations higher than 0.6 ng m(
      3) showed an important contribution of anthropogenic pollution sources increasing
      their negative impact on human health.

PMID- 22398667
TI  - The role of ghrelin, neuropeptide Y and leptin peptides in weight gain after deep
      brain stimulation for Parkinson's disease.
AB  - BACKGROUND: The exact mechanism of weight gain (WG) after deep brain stimulation
      (DBS) of the subthalamic nucleus (STN) in patients with idiopathic Parkinson's
      disease remains unknown. OBJECTIVES: To investigate a possible involvement of
      ghrelin, neuropeptide Y (NPY) and leptin in WG after DBS. METHODS: Twenty-three
      Parkinson patients were submitted for body composition measurements and blood
      sampling 3 days before, and 3 and 6 months after STN DBS. Peripheral
      concentrations of ghrelin, NPY, and leptin were determined, as well as the L-dopa
      equivalent daily dose. Patients were clinically evaluated using the Unified
      Parkinson's Disease Rating Scale. RESULTS: Three months after surgery, a
      significant WG was observed (3.09 +/- 5.00 kg; p = 0.007) with no further
      increase at 6 months. Three months postoperatively, NPY circulating levels
      increased significantly (p = 0.05), while the increase of ghrelin levels reached
      statistical significance at 6 months (p = 0.001). WG was significantly associated
      with changes of ghrelin and leptin levels at 3 and 6 months, respectively.
      CONCLUSIONS: STN DBS seems to temporarily dysregulate the hypothalamic secretion
      of NPY and ghrelin. The variation of weight may be attributed to an increased
      production of ghrelin and leptin. A possible neuroprotective role of DBS, exerted
      through the increase of ghrelin levels, should be further studied.

PMID- 22398668
TI  - Loading effect of 200 mg cilostazol on platelet inhibition in patients undergoing
      percutaneous coronary intervention.
AB  - To date, most studies conducted on cilostazol have examined its effects as an
      agent of maintenance-dose therapy, but its loading effects on platelet inhibition
      have never been reported. This study aimed to determine the loading effects of
      200 mg cilostazol in addition to aspirin and clopidogrel on platelet inhibition
      in patients undergoing percutaneous coronary intervention.Sixty consecutive
      patients undergoing coronary intervention were enrolled and assigned to receive
      300 mg of aspirin and clopidogrel with or without 200 mg of cilostazol. All
      loading doses were given at least 3 hours before percutaneous coronary
      intervention and followed by dual or triple maintenance-dose therapy. Platelet
      function tests were performed just before and at 24 hours and 30 days after
      percutaneous coronary intervention by light transmittance aggregometry and
      VerifyNow(r) P2Y12 assay.There were no significant differences in baseline or
      angiographic characteristics between the 2 groups. The results of platelet
      function tests revealed that the adjunctive loading dose of 200 mg of cilostazol
      induced more potent platelet inhibition compared to a dual regimen at each time
      point. Cilostazol reduced the incidence of high post-treatment platelet
      reactivity (HPPR).Adjunctive 200 mg cilostazol can improve platelet
      responsiveness to clopidogrel in the pre- and postprocedural phases, reducing the
      prevalence of HPPR.

PMID- 22398669
TI  - Body surface two-dimensional spectral map of atrial fibrillation using vector
      projected 187 channel electrocardiography.
AB  - Atrial cycle length during atrial fibrillation and flutter waves may be
      correlated with atrial refractoriness and organization. The nature of the
      frequency by spectral analysis may reflect a profile of atrial cycle length. In
      this study, we developed a novel body surface 2-dimensional spectral map during
      fibrillation using vector-projected 187 channel ECG (187ch VP-ECG).The study
      consisted of 28 patients (24 with atrial fibrillation (AFIB) and 4 atrial flutter
      (AFL) with valvular heart disease). We performed spectral analysis by maximum
      entropy modeling (MEM) in 4 second nonaveraged 187ch electrical current waves by
      187ch VP-ECG. Body surface spectral features were displayed according to the
      frequency and power magnitude components. We verified the accuracy of the
      spectral features by a 64ch magnetocardiography (MCG). The average dominant
      frequency in AFL by 187ch VP-ECG was lower than those in AFIB (4.6 +/- 0.9 Hz in
      AFL, 7.2 +/- 0.9 Hz in AFIB, P < 0.01). Comparison of average dominant frequency
      between 187ch VP-ECG and 64 ch MCG demonstrated good agreement (y = 0.86x+0.84,
      r(2) = 0.89, P < 0.0001). Body surface 2-dimensional spectral features
      demonstrated homogenous spectrum patterns in AFL, and in-homogenous spectrum
      patterns in AFIB.In conclusion, novel body surface spectral mapping using 187ch
      VP-ECG may represent a 2-dimensional spectral feature that may be related to
      atrial refractoriness and organization.

PMID- 22398670
TI  - Edema index-guided disease management improves 6-month outcomes of patients with
      acute heart failure.
AB  - The efficacy of heart failure (HF) management programs is compromised by the
      challenge of early identification of patients at imminent risk. Segmental
      multifrequency bioelectrical impedance analysis can generate an "edema index"
      (EI) as a surrogate for the body fluid status. In this study, we tested whether
      integration of EI-guided management improved the 6-month outcomes of HF patients
      under multidisciplinary care. In total, 159 patients with acute HF were
      randomized into control, case management (CM), and EI-guided CM (EI) groups (n =
      53 in each group). In the EI group, a management algorithm was designed based on
      the measured EI. The analyzed endpoints included HF-related and all cause-related
      events during the 6-month follow-up period. In the 6 months, there were 11 (6.9%)
      deaths, 19 (11.9%) HF-related rehospitalizations, and 45 (28.3%) all-cause
      related rehospitalizations. Compared to the control (26.4%) and CM groups
      (15.1%), the EI group had a lower rate of HF-related death and rehospitalization
      (3.8%, P = 0.004).  Multivariate analysis revealed that EI-guided management was
      an independent predictor of a lower HF-related event rate (hazard ratio = 0.15,
      95%CI = 0.03~0.66, P = 0.012). Patients with a higher pre-discharge EI were
      older, had lower blood albumin and hemoglobin levels, and had a higher functional
      class and incidences of diabetes mellitus and chronic kidney disease. An increase
      in the pre-discharge EI by 0.001 increased the HF-related event rate by 6% (P =
      0.002). Use of EI-guided management lowered this risk (P = 0.03). In conclusion,
      an EI-based HF management program demonstrated an event-lowering effect superior
      to traditional nurse-led multidisciplinary care in 6 months after an acute HF
      episode.

PMID- 22398671
TI  - Left atrial volume by echocardiography in patients with false positive myocardial
      perfusion scans.
AB  - A stress-induced myocardial perfusion abnormality (MPS), in the absence of
      angiographically significant epicardial coronary artery disease, is considered a
      "false-positive" test result. We hypothesized that echocardiography would provide
      complementary prognostic and pathophysiologic data relevant to the management of
      patients with MPS and normal coronary angiograms. Accordingly, left atrial volume
      index (LAVi) was assessed by echocardiography in 38 patients with false positive
      MPS as defined by normal coronary angiograms and 26 patients with true negative
      MPS from a total of 1,356 patients stressed from July 2006-May 2008.
      Pathologically abnormal elevation of LAVi (>= 32 mL/m(2)) was observed in 16 of
      19 women (84%) and 11 of 19 men (58%) in the false positive MPS (FPMPS) group
      while none of the patients in the true negative MPS (TNMPS) group had elevated
      LAVi. In the FPMPS group mean LAVi was significantly higher in women than men
      (40.64 +/- 11.4 mL/m(2) versus 32.6 +/- 10.5 mL/m(2), P = 0.01). The mean LAVi in
      the FPMPS group was significantly different from the TNMPS group (36.6 +/- 11.6
      versus 21 +/- 7 mL/m(2), P = 0.000). A stepwise logistic regression determined
      BSA, LAV and LAVi as useful in predicting false positive and true negative MPS.
      All three were significant predictors (P < 0.01) and the area under the ROC curve
      was 0.91. Our findings in this relatively small cohort suggest that patients with
      false positive MPS have a greater increased LAVi.

PMID- 22398672
TI  - Role of coronary CT angiography in asymptomatic patients with type 2 diabetes
      mellitus.
AB  - Diabetic patients with coronary artery disease are often asymptomatic, making
      appropriate care of such patients difficult. The purpose of this study was to
      investigate the prevalence of coronary lesions in asymptomatic diabetic patients.
      Coronary computed tomography (CT) angiography was performed in 120 consecutive
      diabetic patients (90 of whom were men, mean age 65, mean HbA1c 7.2%). Images
      from patients whose coronary artery calcium scores (CAC scores) were less than
      400 were subjected to stenosis and plaque analysis. Significant stenosis was
      defined as coronary artery stenosis > 70%. High-risk plaque was defined as plaque
      having both a CT density < 30 Hounsfield Units (HU) and showing positive
      remodeling. Significant stenoses were identified in 30.5% of the patients. High
      risk plaques were identified in 17.1% of the patients. Less than half of the high
      risk plaques were obstructive plaques. There was a statistically significant
      association between significant stenosis and high-risk plaque by chi-square test
      (P = 0.022). We found significant stenosis even in patients whose CAC score = 0
      at a rate of 5.0%. Using univariate logistic-regression analysis, we found that
      coronary risk factors associated with significant stenosis and high-risk plaque
      were dyslipidemia (P = 0.033) and current smoking (P = 0.030), respectively. We
      report for the first time, the prevalence of high-risk plaques in the arteries of
      patients with asymptomatic diabetes, as assessed by coronary CT angiography.

PMID- 22398673
TI  - Cholesterol and triglyceride concentrations in lipoproteins as related to carotid
      intima-media thickness.
AB  - Since distinct cholesterol and triglyceride concentrations in major lipoproteins
      and their subclasses may be related to atherosclerosis, we investigated the
      relationship of cholesterol and triglyceride concentrations in lipoprotein
      subclasses and the severity of carotid intima-media thickness (IMT), a surrogate
      marker of subclinical atherosclerosis. We studied 116 apparently healthy Japanese
      men (53 +/- 9 years) without a history of cardiovascular diseases who were not
      taking any medication. Carotid IMT was measured by means of high-resolution
      vascular ultrasound. Plasma cholesterol and triglyceride concentrations in major
      lipoproteins and their subclasses were determined by HPLC with gel permeation
      columns. By univariate analyses, carotid IMT was the most closely related to age
      (r = 0.528, P < 0.001), followed by smoking habit expressed as pack-year
      cigarette consumption (r = 0.409, P < 0.001). In addition to total cholesterol
      and LDL cholesterol, carotid IMT was significantly associated with cholesterol
      and triglyceride concentrations in several LDL and VLDL subclasses. Stepwise
      multiple linear regression analysis revealed that age (beta = 0.436, P < 0.001),
      smoking (pack-years) (beta = 0.225, P = 0.007), and large LDL cholesterol (beta =
      0.175, P = 0.023) were independent predictors of determining carotid IMT
      (adjusted R(2) = 0.347, P < 0.001). These results indicate that large LDL
      cholesterol is an important, independent determinant of carotid IMT in healthy
      men.

PMID- 22398674
TI  - Development and implementation of an advanced coronary angiography and
      intervention database system.
AB  - The 'evidence' in evidence-based medicine (EBM) is often limited to knowledge
      obtained from randomized controlled clinical trials (RCT). Most RCTs, however,
      have strict enrollment criteria which make patient background characteristics and
      clinical histories significantly different from those encountered in actual
      practice. Thus it is important to accumulate and analyze data obtained in daily
      practice to gain insight into a larger clinical picture. Recent developments in
      information technology and its lowered cost have enabled us to record clinical
      activity in much greater detail at a lower cost. These factors prompted us to
      design and develop a coronary angiography and intervention reporting system
      (CAIRS) to collect data and analyze outcomes of coronary intervention. The
      resulting advanced CAIRS can record detailed data on coronary angiographic and
      interventional procedures.To date, data on 10,025 cases of coronary angiography,
      of which 3,574 were interventional, have been collected over a 5.5 year period.
      There were 4,343 unique patients, 3,115 (71.7%) of which were male. The overall
      mean age was 67.0 +/- 11.5. The mean age of males was 66.3 +/- 11.4 and that of
      females was 69.0 +/- 11.4. About one-third of the patients never underwent a PCI
      procedure at our institution. For patients that underwent at least one PCI
      procedure at our institution, the prescription rate of statin increased from
      50.8% in 2005 to 80.3% in 2011, while those of nitrate and ticlopidine decreased
      from 36.7% and 90.8% in 2005 to 21.3% and 0.8% in 2011, respectively. We have
      also implemented the same system at another institution and compared the data on
      stent usage between the two institutions, which revealed vastly different stent
      usage profiles.In conclusion, we have successfully developed and implemented an
      advanced coronary angiography and intervention reporting system which we call
      CAIRS. Implementing the same system at multiple institutions and analyzing data
      collected from several institutions will provide detailed and timely insight into
      the 'real world' of coronary angiography and interventional procedures and their
      outcome.

PMID- 22398675
TI  - beta-actin-positive mononuclear cells participate in coronary microvascular
      medial hyperplasia by migrating through adventitia into media, with special
      reference to microvessel angina.
AB  - Coronary microvascular hyperplasia is a cause of microvessel angina, although the
      underlying cellular mechanisms remain unclear. We examined how mononuclear cells
      expressing beta-actin (beta-MNCs), which were identified in coronary vessels,
      induce coronary microvascular hyperplasia.The presence of beta-MNCs in coronary
      hyperplastic arterial (HAM) and venous microvessels (HVM) was examined by
      endomyocardial biopsy in 25 patients with suspected microvessel angina. beta-MNCs
      were identified in 14 HAMs obtained from 11 patients. Basic fibroblast growth
      factor and heparin sulfate were injected into the infarcted myocardium to induce
      HAM and HVM in 28 beagles, and then we examined the role of beta-MNCs in the
      onset of HAM and HVM. The following changes were observed after infarction
      induction in beagles: (a) migration of beta-MNCs from the existing microvessels
      into the interstitial space at 1-2 weeks; (b) those traversing the adventitia
      into the media, but not intima, of microvessels; (c) their transformation to
      smooth muscle cells (SMCs) and/or connective tissues (collagen and elastin
      fibers); (d) and medial hyperplasia without intimal hyperplasia. Medial
      hyperplasia was classified into SMC-proliferative and both SMC- and connective
      tissue-proliferative types. beta-MNCs expressed CD(34) but did not express other
      major vessel-related cell markers.beta-MNCs are a vascular progenitor, and
      migrate out of the adventitia into media, and participate in the etiology of
      coronary microvascular medial hyperplasia.

PMID- 22398676
TI  - Migration of mononuclear cells expressing beta-actin through the adventitia into
      media and intima in coronary arteriogenesis and venogenesis in ischemic
      myocardium.
AB  - It was previously thought that arteriogenesis and venogenesis are induced not
      only by proliferation of vessel-resident smooth muscle cells (SMCs) and
      endothelial cells (ECs) but also by migration of their precursors. However, it is
      not well understood through what route(s) the precursors migrate into the
      existing vessels.We examined through what route or routes circulating mononuclear
      cells expressing beta-actin (beta-MNCs), which we identified in canine coronary
      vessels, migrate into coronary vessel walls and cause arteriogenesis and
      venogenesis at 1, 2, 4 and 8 weeks after induction of myocardial infarction.The
      following changes were observed: (1) The beta-MNCs migrated via coronary
      microvessels to the interstitial space at one week; (2) beta-MNCs traversed the
      adventitia into the media and settled in parallel with pre-existing smooth muscle
      cells (SMCs) in arterioles and arteries and lost beta-actin and acquired alpha
      smooth muscle actin (alpha-SMA) to become mature SMCs at 2-4 weeks; (3) at the
      same time, other beta-MNCs migrated across the adventitia and media into the
      intima and settled in parallel with pre-existing endothelial cells (ECs) and lost
      beta-actin, while acquiring CD(31), to become mature ECs, resulting in
      arteriogenesis; (4) Similarly, beta-MNCs migrated into venular and venous walls
      and became SMCs or ECs, resulting in venogenesis.beta-MNCs in the interstitial
      space expressed CD(34) but not other major vascular cell markers.beta-MNCs,
      possibly a vascular progenitor, migrate not from the lumen but across the
      adventitia into the media or intima of coronary vessels and transit to SMCs or
      ECs, and participate in arteriogenesis and venogenesis in ischemic myocardium.

PMID- 22398677
TI  - A prostacycline analog prevents chronic myocardial remodeling in murine cardiac
      allografts.
AB  - ONO-1301MS is a compound that acts as a prostacyclin agonist with thromboxane A2
      synthase inhibitory activity. We investigated the effect of ONO-1301MS on
      myocardial remodeling in murine cardiac allografts. The hearts of Balb/c mice
      were transplanted into C3H/He mice (a full allomismatch combination) to assess
      acute rejection or C57BL/6 hearts into B6.C-H2(<bm12>) KhEg (a class II mismatch
      combination) to examine chronic rejection. ONO-1301MS did not prolong full
      allomismatch cardiac graft survival. Severe myocardial fibrosis with high
      collagen concentration was observed in untreated class II mismatch allografts on
      day 60. However, significantly suppressed myocardial fibrosis with less collagen
      synthesis was observed in the ONO-1301MS-treated group compared to the control
      group. ONO-1301MS could be an effective strategy to suppress chronic myocardial
      remodeling in cardiac transplantation.

PMID- 22398678
TI  - Coronary arterial wall disruption and intramural hematoma in a patient with
      coronary spastic angina.
AB  - Acute myocardial infarction is sometimes complicated in patients with coronary
      spastic angina. The mechanisms are known to be plaque rupture and thrombosis
      induced by spasm, and reduced coronary flow due to prolonged spasm. We describe
      the case of a 45-year-old woman with coronary spastic angina who had a
      complication of an acute myocardial infarction. A specimen obtained with
      thrombectomy was the disrupted coronary artery wall accompanied by massive
      intramural hemorrhage. The cause of the acute myocardial infarction was thought
      to be an embolism of the coronary arterial wall that was disrupted by spasm and
      intramural hemorrhage.

PMID- 22398679
TI  - Preliminary report of tolvaptan treatment in Japanese patients with heart
      failure.
AB  - While diuretic drugs are commonly used in patients with congestive heart failure,
      the efficacy of their long-term use still remains controversial. Recently, a new
      class of diuretics, vasopressin receptor 2 antagonists, has been launched, and
      tolvaptan is one such drug. We describe our initial experience with this novel
      agent. Tolvaptan is potentially useful for treatment of heart failure patients
      with fluid overload who are refractory to conventional diuretic therapies.

PMID- 22398680
TI  - Myocardial involvement in patients with osteogenesis imperfecta.
AB  - Mitral and aortic valve regurgitation is commonly found in osteogenesis
      imperfecta (OI) patients, however, little is known about the myocardial
      involvement in this disorder. An 82-year-old man with OI developed heart failure
      and was admitted to our hospital. Echocardiogram revealed severe mitral
      regurgitation without left ventricular (LV) dilatation, but with LV wall
      thickening. Histological analysis exhibited interstitial fibrosis of the
      myocardium in addition to myxoid changes of the mitral leaflet. These findings
      suggest that OI patients may develop LV remodeling together with diastolic
      dysfunction.

PMID- 22398681
TI  - Inhibiting rotavirus infection by membrane-impermeant thiol/disulfide exchange
      blockers and antibodies against protein disulfide isomerase.
AB  - OBJECTIVES: Determining the effect of membrane-impermeant thiol/disulfide
      exchange inhibitors on rhesus rotavirus infectivity in MA104 cells and
      investigating protein disulfide isomerase (PDI) as a potential target for these
      inhibitors. METHODS: Cells were treated with DTNB [5,5-dithio-bis-(2-nitrobenzoic
      acid)], bacitracin or anti-PDI antibodies and then infected with virus. Triple
      layered particles (TLPs) were also pretreated with inhibitors before inoculation.
      The effects of these inhibitors on alpha-sarcin co-entry, virus binding to cells
      and PDI-TLP interaction were also examined. FACS analysis, cell-surface protein
      biotin-labeling, lipid-raft isolation and ELISA were performed to determine cell
      surface PDI expression. RESULTS: Infectivity became reduced by 50% when cells or
      TLPs were treated with 1 or 6 mM DTNB, respectively; infectivity became reduced
      by 50% by 20 mM bacitracin treatment of cells whereas TLPs were insensitive to
      bacitracin treatment; anti-PDI antibodies decreased viral infectivity by about
      45%. The presence of DTNB (2.5 mM) or bacitracin (20 mM) was unable to prevent
      virus binding to cells and rotavirus-induced alpha-sarcin co-entry. CONCLUSIONS:
      It was concluded that thiol/disulfide exchange was involved in rotavirus entry
      process and that cell-surface PDI was at least a potential target for DTNB and
      bacitracin-induced infectivity inhibition.

PMID- 22398682
TI  - Challenge of isolated sputum cells supports in vivo origin of intolerance
      reaction to aspirin/non-steroidal anti-inflammatory drugs in asthma.
AB  - BACKGROUND: There is no in vitro test to diagnose aspirin-intolerant asthma
      (AIA). The aim of this study was to test if challenge with aspirin of sputum
      cells from subjects with AIA triggers the release of cysteinyl leukotrienes
      (CysLTs), known to be mediators of bronchoconstriction in AIA. METHODS: Sputum
      induction was performed at baseline and at another visit 2 h after a lysine
      aspirin bronchoprovocation in 10 subjects with AIA and 9 subjects with aspirin
      tolerant asthma (ATA). The isolated sputum cells were incubated for ex vivo
      challenge. RESULTS: Release of CysLTs by sputum cells from patients with AIA was
      not induced by lysine-aspirin ex vivo, neither when cells were collected at
      baseline nor in sputum cells recovered after lysine-aspirin-induced
      bronchoconstriction, whereas release of CysLTs from sputum cells was triggered by
      an ionophore on both occasions. However, the CysLT levels elicited by the
      ionophore were higher in the AIA group both at baseline (AIA vs. ATA: 3.3 vs. 1.6
      ng/million cells; p < 0.05) and after the lysine-aspirin bronchoprovocation (3.9
      vs. 1.7 ng/million cells; p < 0.05). This difference in the amount of CysLTs
      released between the groups appeared to be related to the number of eosinophils.
      CONCLUSIONS: Intolerance to aspirin could not be triggered in sputum cells
      isolated from subjects with AIA. Together with the previous inability to
      demonstrate intolerance to non-steroidal anti-inflammatory drugs in isolated
      blood cells, these results support the requirement of tissue-resident cells in
      the adverse reaction. However, ex vivo stimulation of sputum cells may be
      developed into a new test of capacity for LT release in inflammatory cells
      recovered from airways.

PMID- 22398683
TI  - Online prediction of others' actions: the contribution of the target object,
      action context and movement kinematics.
AB  - Previous research investigated the contributions of target objects, situational
      context and movement kinematics to action prediction separately. The current
      study addresses how these three factors combine in the prediction of observed
      actions. Participants observed an actor whose movements were constrained by the
      situational context or not, and object-directed or not. After several steps,
      participants had to indicate how the action would continue. Experiment 1 shows
      that predictions were most accurate when the action was constrained and object
      directed. Experiments 2A and 2B investigated whether these predictions relied
      more on the presence of a target object or cues in the actor's movement
      kinematics. The target object was artificially moved to another location or
      occluded. Results suggest a crucial role for kinematics. In sum, observers
      predict actions based on target objects and situational constraints, and they
      exploit subtle movement cues of the observed actor rather than the direct visual
      information about target objects and context.

PMID- 22398684
TI  - Displacement of location in illusory line motion.
AB  - Six experiments examined displacement in memory for the location of the line in
      illusory line motion (ILM; appearance or disappearance of a stationary cue is
      followed by appearance of a stationary line that is presented all at once, but
      the stationary line is perceived to "unfold" or "be drawn" from the end closest
      to the cue to the end most distant from the cue). If ILM was induced by having a
      single cue appear, then memory for the location of the line was displaced toward
      the cue, and displacement was larger if the line was closer to the cue. If ILM
      was induced by having one of two previously visible cues vanish, then memory for
      the location of the line was displaced away from the cue that vanished. In
      general, the magnitude of displacement increased and then decreased as retention
      interval increased from 50 to 250 ms and from 250 to 450 ms, respectively.
      Displacement of the line (a) is consistent with a combination of a spatial
      averaging of the locations of the cue and the line with a relatively weaker
      dynamic in the direction of illusory motion, (b) might be implemented in a
      spreading activation network similar to networks previously suggested to
      implement displacement resulting from implied or apparent motion, and (c)
      provides constraints and challenges for theories of ILM.

PMID- 22398686
TI  - Who provides accelerometry data? Correlates of adherence to wearing an
      accelerometry motion sensor: the 2008 Health Survey for England.
AB  - BACKGROUND: Use of objective physical activity measures is rising. We
      investigated the representativeness of survey participants who wore an
      accelerometer. METHODS: 4273 adults aged 16+ from a cross-sectional survey of a
      random, nationally representative general population sample in England in 2008
      were categorized as 1) provided sufficient accelerometry data [4-7 valid days
      (10+ hrs/d), n = 1724], 2) less than that (n = 237), or 3) declined (n = 302).
      Multinomial logistic regression identified demographic, socioeconomic, health,
      lifestyle, and biological correlates of participants in these latter 2 groups,
      compared with those who provided sufficient accelerometry data (4+ valid days).
      RESULTS: Those in the random subsample offered the accelerometer were older and
      more likely to be retired and to report having a longstanding limiting illness
      than the rest of the adult Health Survey for England participants. Compared with
      those providing sufficient accelerometry data, those wearing the accelerometer
      less were younger, less likely to be in paid employment, and more likely to be a
      current smoker. Those who declined to wear an accelerometer did not differ
      significantly from those who wore it for sufficient time. CONCLUSIONS: We found
      response bias in wearing the accelerometers for sufficient time, but refusers did
      not differ from those providing sufficient data. Differences should be
      acknowledged by data users.

PMID- 22398685
TI  - The calm mouse: an animal model of stress reduction.
AB  - Chronic stress is associated with negative health outcomes and is linked with
      neuroendocrine changes, deleterious effects on innate and adaptive immunity, and
      central nervous system neuropathology. Although stress management is commonly
      advocated clinically, there is insufficient mechanistic understanding of how
      decreasing stress affects disease pathogenesis. Therefore, we have developed a
      "calm mouse model" with caging enhancements designed to reduce murine stress.
      Male BALB/c mice were divided into four groups: control (Cntl), standard caging;
      calm (Calm), large caging to reduce animal density, a cardboard nest box for
      shelter, paper nesting material to promote innate nesting behavior, and a
      polycarbonate tube to mimic tunneling; control exercise (Cntl Ex), standard
      caging with a running wheel, known to reduce stress; and calm exercise (Calm Ex),
      calm caging with a running wheel. Calm, Cntl Ex and Calm Ex animals exhibited
      significantly less corticosterone production than Cntl animals. We also observed
      changes in spleen mass, and in vitro splenocyte studies demonstrated that Calm Ex
      animals had innate and adaptive immune responses that were more sensitive to
      acute handling stress than those in Cntl. Calm animals gained greater body mass
      than Cntl, although they had similar food intake, and we also observed changes in
      body composition, using magnetic resonance imaging. Together, our results suggest
      that the Calm mouse model represents a promising approach to studying the
      biological effects of stress reduction in the context of health and in
      conjunction with existing disease models.

PMID- 22398687
TI  - Intrauterine upper extremity thrombosis successfully treated with recombinant
      tissue plasminogen activator, enoxaparin and collagenase.
AB  - Intrauterine ischemia of the limbs is a rare condition involving thrombosis and
      ischemia of the extremities before birth. The clinical presentation depends on
      the extremity affected as well as the timing of thrombosis. Very few cases with
      extremity hypoperfusion and gangrene due to intrauterine thrombosis have been
      reported in the literature, and therefore there is no consensus on the optimal
      therapeutic strategy for such cases. Presented here is a case of a newborn with
      intrauterine brachial arterial thrombosis of the right upper extremity who was
      successfully treated by a combination of recombinant tissue plasminogen
      activator, enoxaparin and collagenase application followed by surgery.

PMID- 22398688
TI  - Maximizing time-resolved MRA for differentiation of hemangiomas, vascular
      malformations and vascularized tumors.
AB  - Contrast-enhanced magnetic resonance angiography (MRA) using time-resolved
      imaging is a relatively new and increasingly popular technique. We will describe
      the technique utilized at our institution, Time-Resolved Imaging of Contrast
      Kinetics (TRICKS; GE Healthcare, Milwaukee, WI), and the parameters that can be
      adjusted to optimize the exam. We will review key imaging features of hemangiomas
      and vascular malformations in various modalities, with a special emphasis on the
      TRICKS appearance.

PMID- 22398689
TI  - Highlights in metastatic breast cancer from the 2011 San Antonio Breast Cancer
      Symposium (SABCS).

PMID- 22398690
TI  - Degradation of imidacloprid in chrysanthemi flos and soil.
AB  - Degradation of imidacloprid in chrysanthemi flos and cultivated soil was studied.
      The half-lives of imidacloprid were 3.55-5.17 days (soil), 2.10-3.98 days (fresh
      buds and flowers), 22.14 days (dry flowers, 5 degrees C) and 13.08 days (dry
      flower, 20 degrees C), separately. The temperature can affect imidacloprid
      degradation in soil and dry chrysanthemum buds and flowers. Imidacloprid residues
      in chrysanthemum flowers were more stable during store stage than growing one.
      Few imidacloprid residues would be dissolved into chrysanthemum tea liquor when
      the residue in dry buds or dry flowers was below 0.8 mg/kg.

PMID- 22398691
TI  - Dissipation and residues of the herbicide mesotrione in maize and soil in open
      field.
AB  - The purpose of this article was to establish a simple residue analysis method for
      mesotrione in maize using high performance liquid chromatography tandem mass
      spectrometry. The method was then used to study the dissipation and residues in
      maize seedling and soil. The half-lives of mesotrione in maize plants and soil
      were 1.37, 4.31 days in Beijing, and 0.97, 1.80 days in Shandong, respectively.
      The ultimate residues of mesotrione were undetected in soil, maize grain and stem
      at the harvest time, suggesting that mesotrione could be safely used in maize
      crops with an appropriate dosage and application.

PMID- 22398692
TI  - Phenyltins in surface sediments of the Visakhapatnam harbour, India.
AB  - Twenty-two surface sediment samples were collected from Visakhapatnam harbour,
      east coast of India, and analysed for monophenyltin (MPT), diphenyltin (DPT),
      triphenyltin (TPT), total bacteria, and TPT tolerant bacteria. Concentrations of
      MPT, DPT and TPT varied between 1-26, 3-28, and 0.31-145 ng Sn g(-1) dry wt,
      respectively. Phenyltin concentrations were influenced by ship related
      activities, agricultural waste and sewage. These phenyltin concentrations
      indicate sediments are contaminated. Abundance of TPT tolerant bacteria was
      strongly influenced by the levels of phenyltins.

PMID- 22398693
TI  - Determination of six neonicotinoid insecticides residues in spinach, cucumber,
      apple and pomelo by QuEChERS method and LC-MS/MS.
AB  - A modified QuEChERS and LC-MS/MS method has been developed for the simultaneous
      determination of residues of six neonicotinoids in various crops, including
      spinach, cucumber, apple and pomelo. The method showed good linearity (R(2) >=
      0.9995) and precision (RSD <= 14.0%). Average recoveries of the six
      neonicotinoids ranged between 73.7% and 103.8% at spiking levels 0.005, 0.1 and 1
      mg kg(-1). The LODs and LOQs were in the ranges of 0.20-0.85 MUg kg(-1) and 0.66
      2.84 MUg kg(-1), respectively. The method was satisfactorily validated for the
      analysis of 50 agricultural samples. Imidacloprid and imidaclothiz were detected
      at concentration levels ranging from 7 to 5.3 MUg kg(-1).

PMID- 22398694
TI  - Electro-catalytic oxidative cleavage of lignin in a protic ionic liquid.
AB  - Lignin is a component of lignocellulosic biomass and a promising matrix for
      recovering important renewable aromatic compounds. We present a new approach of
      electro-oxidative cleavage of lignin, dissolved in a special protic ionic liquid,
      using an anode with particular electro-catalytic activity. As appropriate ionic
      liquid triethylammonium methanesulfonate was identified, synthesised, explored
      for dissolution of alkali-lignin and used for electrolysis of 5 wt.% lignin
      solutions. As appropriate anode material, oxidation-stable ruthenium-vanadium
      titanium mixed oxide electrodes were prepared and explored for their electro
      catalytic activity. The electrolysis was performed at several potentials in the
      range from 1.0 V to 1.5 V (vs. an Ag pseudo reference electrode). A wide range of
      aromatic fragments was identified as cleavage products by means of GC-MS and HPLC
      measurements.

PMID- 22398695
TI  - Selective detection of Fe2+ by combination of CePO4:Tb3+ nanocrystal-H2O2 hybrid
      system with synchronous fluorescence scan technique.
AB  - A new method for quenching kinetic discrimination of Fe(2+) and Fe(3+), and
      sensitive detection of trace amount of Fe(2+) was developed by using synchronous
      fluorescence scan technique. The principle of this assay is based on the
      quenching kinetic discrimination of Fe(2+) and Fe(3+) in CePO(4):Tb(3+)
      nanocrytals-H(2)O(2) hybrid system and the Fenton reaction between Fe(2+) and
      H(2)O(2). Stable, water-soluble and well-dispersible CePO(4):Tb(3+) nanocrystals
      were synthesized in aqueous solutions, and characterized by transmission electron
      microscopy (TEM) and electron diffraction spectroscopy (EDS). We found that both
      Fe(2+) and Fe(3+) could quench the synchronous fluorescence of CePO(4):Tb(3+)
      nanocrytals-H(2)O(2) system, but their quenching kinetics velocities were quite
      different. In the presence of Fe(3+), the synchronous fluorescent intensity was
      unchanged after only one minute, but in the presence of Fe(2+), the synchronous
      fluorescent intensity decreased slowly until 28 min later. The Fenton reaction
      between Fe(2+) and H(2)O(2) resulted in hydroxyl radicals which effectively
      quenched the synchronous fluorescence of the CePO(4):Tb(3+) nanocrystals due to
      the oxidation of Ce(3+) into Ce(4+) by hydroxyl radicals. Under optimum
      conditions, the linear range for Fe(2+) is 3 nM-2 MUM, and the limit of detection
      is 2.0 nM. The method was used to analyze water samples.

PMID- 22398696
TI  - Long waiting period to enter methadone maintenance treatment: relation to patient
      characteristics and outcome.
AB  - Methadone maintenance treatment is a chronic treatment for opiate addicts. After
      having reached full capacity, new admissions to our clinic were delayed (through
      a waiting list) for all but opiate addicts with HIV and pregnant women. We
      compared characteristics and outcomes between patients admitted without delay
      (1993-2002) and those admitted through a waiting list (2003-2009). All 704
      patients admitted between June 1993 and June 2009 were followed up until June
      2010. There were 470 patients in the early period and 234 in the late period (56
      patients were admitted immediately and 178 after 1.1 +/- 0.8 years of waiting).
      Predictors for 1-year retention in treatment (logistic regression model) were if
      a patient self-referred during the late period, on a waiting list. The waiting
      list patient group was characterized by older age and self-referral - two known
      independent predictors of better retention that were attributed to their superior
      retention rate.

PMID- 22398697
TI  - Seasonal variation for the ratio of BaP to BeP at different sites in Great Xiamen
      Bay.
AB  - From March 2008 to February 2009, PM(10) samples were collected and analyzed for
      polycyclic aromatic hydrocarbons (PAHs) at eight sampling sites in Great Xiamen
      Bay, China. Analyses of the seasonal and spatial variations of these compounds
      revealed the following results. Significantly high levels of PAHs were found in
      the winter compared to the summer, sometimes exceeding 100 ng m(-3), and the
      spatial variations were influenced most by the sampling site surroundings.
      Composition profiles of PAHs of an urban and a rural site were shown to be very
      similar with a positive correlation coefficient larger than 0.9 at the 0.01 level
      of significance for the same season. Diagnostic ratios, together with principal
      component and multiple linear regression analysis, showed that more PAHs were
      from grass/wood/coal combustion in winter than in other seasons. The ratios of
      benzo[a]pyrene to benzo[e]pyrene (BaP-BeP) in winter and fall were 0.6-1.7 times
      higher than those in spring and summer, suggesting the importance of local
      emissions of PAHs. The BaP-BeP ratios in Kinmen were generally lower than those
      in Xiamen, indicating that the aging degree of PAHs was higher in Kinmen than in
      Xiamen. The external input of PAHs from upwind urban and industrial areas was one
      of the key factors causing high levels of PAHs in PM(10) in Great Xiamen Bay in
      winter.

PMID- 22398698
TI  - delta(15)N and delta(13)C in hair from newborn infants and their mothers: a
      cohort study.
AB  - INTRODUCTION: Protein intake in fetal life or infancy may play a key role in
      determining early growth rate, a determinant of later health and disease.
      Previous work has indicated that hair isotopic composition is influenced by diet
      and protein intake. METHODS: This study analyzes the isotopic composition of hair
      obtained from 239 mother/newborn pairs randomly selected within a larger cohort
      enrolled in a study of pre- and postnatal determinants of the child's development
      and health. The isotopic compositions in nitrogen (delta(15)N) and in carbon
      (delta(13)C) were determined by isotope ratio mass spectrometry. RESULTS: Mother
      and newborn hair delta(15)N were tightly correlated (Pearson r = 0.88). The mean
      delta(15)N and delta(13)C values of hair from newborn infants were significantly
      higher than those for the mothers: 9.7 +/- 0.7 vs. 8.8 +/- 0.60/00 (P < 0.0001)
      for delta(15)N and -20.0 +/- 0.4 vs. -20.4 +/- 0.40/00 (P < 0.0001) for
      delta(13)C. Maternal hair delta(15)N at parturition was slightly and positively
      correlated with estimates of protein intake (r = 0.14, P = 0.04). DISCUSSION:
      Hair delta(15)N of the fetus is both highly dependent on and systematically
      higher than that of the mother. Whether quantitative and qualitative protein
      intake, disease, or hormonal status alter hair delta(15)N at birth remains to be
      determined.

PMID- 22398699
TI  - Tracking the impact of the National Institutes of Health Clinical and
      Translational Science Awards on child health research: developing and evaluating
      a measurement strategy.

PMID- 22398700
TI  - Preterm neonates show marked leukopenia and lymphopenia that are associated with
      increased regulatory T-cell values and diminished IL-7.
AB  - INTRODUCTION: Current advances in neonatology have improved survival among
      preterm and low-birth-weight infants. However, the risk of neonatal death in
      preterm infants is much greater than in full-term neonates and is frequently
      associated with infections. METHODS: Little is known about the immune status of
      preterm neonates; therefore, we analyzed the frequency and absolute counts of
      different immune populations in 211 cord blood samples taken from very-preterm to
      full-term neonates. RESULTS: We found that absolute counts of all the immune
      subsets analyzed (i.e., monocytes, granulocytes, B cells, natural killer (NK)
      cells, CD4(+), and CD8(+) T cells) were markedly lower in preterm infants than in
      full-term infants. Surprisingly, we observed that regulatory T cells (Tregs) were
      the only cell subset that did not decrease in preterm infants, and their
      frequency was even higher than in full-term infants. DISCUSSION: Tregs are
      crucial to maternal-fetal tolerance, but their suppressive role could be also
      implicated in the leukopenia observed in preterm infants. We did not observe
      differences in thymic function, but we found that plasma levels of interleukin
      (IL)-7 and the frequency of its receptor were significantly decreased in preterm
      infants. Our results could help to identify leukopenia and to implement immune
      therapies that significantly diminish mortality in preterm neonates.

PMID- 22398701
TI  - Bumetanide augments the neuroprotective efficacy of phenobarbital plus
      hypothermia in a neonatal hypoxia-ischemia model.
AB  - INTRODUCTION: The NaKCl cotransporter NKCC1 facilitates intraneuronal chloride
      accumulation in the developing brain. Bumetanide (BUM), a clinically available
      diuretic, inhibits this chloride transporter and augments the antiepileptic
      effects of phenobarbital (PB) in neonatal rodents. In a neonatal cerebral hypoxia
      ischemia (HI) model, elicited by right carotid ligation, followed by 90 min 8%
      O(2) exposure in 7-d-old (P7) rats, PB increases the neuroprotective efficacy of
      hypothermia (HT). We evaluated whether BUM influenced the neuroprotective
      efficacy of combination treatment with PB and HT. METHODS: P7 rats underwent HI
      lesioning; 15 min later, all received PB (30 mg/kg), and 10 min later, half
      received BUM (10 mg/kg, PB-HT+BUM) and half received saline (PB-HT+SAL). One hour
      after HI, all were cooled (30  degrees C, 3 h). Contralateral forepaw
      sensorimotor function and brain damage were evaluated 1-4 wk later. RESULTS:
      Forepaw functional measures were close to normal in the PB-HT+BUM group, whereas
      deficits persisted in PB-HT+SAL controls; there were corresponding reductions in
      right cerebral hemisphere damage (at P35, % damage: PB-HT+BUM, 21 +/- 16 vs. 38
      +/- 20 in controls). DISCUSSION: These results provide evidence that NKCC1
      inhibition amplifies PB bioactivity in the immature brain and suggest that
      coadministration of PB and BUM may represent a clinically feasible therapy to
      augment the neuroprotective efficacy of therapeutic HT in asphyxiated neonates.

PMID- 22398702
TI  - Ready fabrication of thin-film electrodes from building nanocrystals for micro
      supercapacitors.
AB  - Thin-film pseudocapacitor electrodes with ultrafast lithium storage kinetics,
      high capacitance and excellent cycling stability were fabricated from
      monodispersed TiO(2) building nanocrystals, providing a novel approach towards
      next-generation micro-supercapacitor applications.

PMID- 22398703
TI  - Shielded battery syndrome: a new hardware complication of deep brain stimulation.
AB  - BACKGROUND: Deep brain stimulation hardware is constantly advancing. The last few
      years have seen the introduction of rechargeable cell technology into the
      implanted pulse generator design, allowing for longer battery life and fewer
      replacement operations. The Medtronic(r) system requires an additional pocket
      adaptor when revising a non-rechargeable battery such as their Kinetra(r) to
      their rechargeable Activa(r) RC. This additional hardware item can, if it
      migrates superficially, become an impediment to the recharging of the battery and
      negate the intended technological advance. AIM: To report the emergence of the
      'shielded battery syndrome', which has not been previously described. METHODS: We
      reviewed our deep brain stimulation database to identify cases of recharging
      difficulties reported by patients with Activa RC implanted pulse generators.
      RESULTS: Two cases of shielded battery syndrome were identified. The first
      required surgery to reposition the adaptor to the deep aspect of the subcutaneous
      pocket. In the second case, it was possible to perform external manual
      manipulation to restore the adaptor to its original position deep to the battery.
      CONCLUSIONS: We describe strategies to minimise the occurrence of the shielded
      battery syndrome and advise vigilance in all patients who experience difficulty
      with recharging after replacement surgery of this type for the implanted pulse
      generator.

PMID- 22398704
TI  - New considerations on the neuromodulatory role of thiamine.
AB  - BACKGROUND: A nonmetabolic role for thiamine in cholinergic neurotransmission has
      long been suggested. The mechanism remains unclear. We sought to extend our
      previous research to elucidate the effect of the thiamine metabolic antagonist,
      oxythiamine, on the release of acetylcholine from the brain. METHODS: The
      potassium-stimulated release of acetylcholine from superfused rat brain slices
      was determined. Hand-cut slices of cerebral cortex were preincubated with
      tritiated choline to label acetylcholine stores. Two periods of stimulation (S1,
      S2) with 50 mmol/l solution for 3.5 min were performed as superfusate was
      collected. During S1, only 50 mmol/l potassium-containing Krebs-bicarbonate
      buffer with 2 mmol/l calcium was used. Using a two-by-two design, S2 consisted of
      exposure to 50 mmol/l potassium with or without 10(-4) mol/l oxythiamine, with or
      without calcium. The S2/S1 ratio was calculated. RESULTS: Oxythiamine enhanced
      the potassium-evoked release of acetylcholine by 60% but only when calcium was
      present in the superfusing medium. CONCLUSION: These data confirm earlier
      findings with oxythiamine on the calcium-mediated synaptic transmission of
      acetylcholine and support a possible neuromodulatory role for thiamine distinct
      from its actions as a cofactor during metabolic processes.

PMID- 22398706
TI  - Incidence and survival trends of uncommon corpus uteri malignancies in the
      Netherlands, 1989-2008.
AB  - INTRODUCTION: Corpus uteri cancer is the most common malignancy of the female
      reproductive tract in industrialized countries, and its incidence is increasing.
      Although most of these tumors are of the common endometrial type, there are also
      many uncommon tumors of the corpus uteri. We examined the incidence and survival
      of patients with uncommon epithelial tumors, carcinosarcomas, and sarcomas of the
      corpus uteri diagnosed since 1989. METHODS: All common and uncommon malignancies
      of the corpus uteri registered in the nationwide population-based Netherlands
      Cancer Registry (NCR) during 1989-2008 were included (n = 30,960). The
      histological subtypes were described according to the Blaustein classification
      system. Age-standardized incidence for 1989-2008 was calculated per 1,000,000
      person-years (p-y), and relative survival was calculated according to the type of
      uncommon tumor. RESULTS: The incidence of corpus uteri malignancies increased
      from 159 to 177 per 1,000,000 p-y, mainly owing to the rise in endometrioid
      adenocarcinomas from 106 to 144 per 1,000,000 p-y. In contrast, the incidence of
      uncommon epithelial endometrial carcinomas (UEECs) decreased from 30 to 13 per
      1,000,000 p-y, although carcinosarcomas increased slightly from 5.1 to 6.9 per
      1,000,000 p-y. Furthermore, a remarkable shift in incidence of endometrial
      stromal cell sarcomas (ESS) was observed from high-grade ESSs to low-grade ESSs
      after 2003. Five-year relative survival for patients with UEEC decreased from 72%
      to 54% and for patients with serous adenocarcinoma from 73% to 51%. Coinciding
      with an increase in the incidence of common adenocarcinoma of the corpus uteri,
      there was a decline in uncommon adenocarcinomas and more or less a stable
      incidence of sarcomas and carcinosarcomas. CONCLUSION: The decrease in UEEC
      tumors consisted largely of fewer serous carcinomas, possibly and likely
      reflecting a more precise histopathological classification of villoglandular
      tumors. Unfortunately, relative survival for patients with UEEC, sarcomas, and
      carcinosarcomas did not improve over the study period, indicating a need for more
      research on treatment strategies for this group of patients.

PMID- 22398705
TI  - Adjuvant chemotherapy for stage I clear cell carcinoma of the ovary: an analysis
      of fully staged patients.
AB  - OBJECTIVE: Although postoperative adjuvant chemotherapy is generally recommended
      for early-stage ovarian cancer, it remains unclear whether adjuvant chemotherapy
      is also effective for clear cell carcinoma (CCC). METHODS: Seventy-three patients
      with stage I CCC of the ovary who had undergone complete surgical staging formed
      the study population (stage IA, 20 patients; stage IC, 53 patients). Survival and
      multivariate analyses were retrospectively performed to determine the
      effectiveness of postoperative chemotherapy in these patients. RESULTS: Of the
      total (73 patients), 30 patients received adjuvant chemotherapy (stage I C
      positive), whereas 43 patients did not (stage I C-negative). The 5-year
      progression-free survival (PFS) and 5-year overall survival (OS) rates for the
      stage I C-positive group were 80.1% and 87.4% compared with 73.9% and 81.7% for
      the stage I C-negative group. The differences in survival between these groups
      were not significant (PFS: P = 0.610; OS: P = 0.557). Four of the patients with
      stage IA CCC underwent chemotherapy, whereas the remaining 16 patients received
      no additional therapy. No recurrence was observed in either group. Of the
      patients with stage IC CCC, 26 patients underwent chemotherapy (stage IC C
      positive) and 27 received no additional therapy (stage IC C-negative). There was
      no statistical difference in PFS and OS between the stage IC C-positive and stage
      IC C-negative groups. Of the patients with stage IC without artificial rupture,
      the 5-year PFS rates of the C-positive and C-negative patients were 69.6% and
      34.6%, respectively, but the 5-year OS rates were 75.0% and 70.0%, respectively
      (not significant). Multivariate analyses confirmed that the presence or absence
      of adjuvant chemotherapy was not a prognostic indicator. CONCLUSIONS: The current
      study was performed only in fully staged patients, suggesting that postoperative
      adjuvant chemotherapy is not necessary for stage IA CCC patients. For patients
      with stage IC CCC patients, adjuvant chemotherapy suppressed recurrence, but the
      effectiveness was insufficient in our limited study. Further studies are required
      to clarify this.

PMID- 22398707
TI  - Incidence and risk factors of lower-extremity lymphedema after radical surgery
      with or without adjuvant radiotherapy in patients with FIGO stage I to stage IIA
      cervical cancer.
AB  - OBJECTIVE: This study aimed to determine the incidence and risk factors of lower
      extremity lymphedema (LEL) in women who had radical surgery with or without
      adjuvant radiotherapy for International Federation of Gynecology and Obstetrics
      (FIGO) stage I to stage IIA cervical cancer. METHODS: The medical records were
      reviewed retrospectively on patients with histologically confirmed FIGO stage I
      to IIA cervical cancer. Lower-extremity lymphedema-related medical problems such
      as peripheral vascular disease, congestive heart failure, or chronic renal
      disease were excluded. A logistic regression analysis was used to examine the
      relationship between variable clinical characteristics and development of LEL.
      RESULTS: We evaluated 707 patients. Of the 707 patients evaluated, we excluded 92
      patients who had received radiotherapy as the initial therapy and 19 patients
      with LEL related to medical problems. Seventy-five patients (12.6%) developed
      LEL. The incidence was high in patients with adjuvant radiotherapy (odds ratio,
      3.47; 95% confidence interval, 2.086-5.788; P = 0.000), with 78.7% of the
      patients with LEL having developed the condition within 3 years after initial
      treatment. CONCLUSIONS: Adjuvant radiotherapy was significantly associated with
      development of LEL in women who had undergone radical surgery with
      lymphadenectomy for FIGO stage I to stage IIA cervical cancer. The possibility
      for the occurrence of LEL must be fully explained before treatment and patients
      should be provided with the appropriate preventive education. Further prospective
      studies are needed to confirm the incidence and risk factors for LEL.

PMID- 22398708
TI  - Clinical recommendation radical trachelectomy for fertility preservation in
      patients with early-stage cervical cancer.
AB  - Radical trachelectomy (RT) is a fertility-sparing procedure with the aim to
      provide adequate oncological safety to patients with cervical cancer while
      preserving their fertility. In the current review, indications, development of
      the procedure, technical aspects, preoperative and postoperative management, and
      oncological, fertility, and obstetric outcomes are discussed and studied with
      respect to whether the procedure is performed abdominally or vaginally.
      Complications of RT, staging, and more conservative alternatives to RT are
      discussed as well. A systematic MEDLINE search was performed, which yielded 218
      articles, of which 75 were selected for further analysis based on the number of
      patients and the quality of the study. Strict morphologic criteria should be
      applied to the candidates to maintain oncological safety. When limited to a tumor
      less than 2 cm in diameter, the overall recurrence rate after vaginal RT is 3% to
      6% and the death rate is 2% to 5%. Data on fertility and obstetric outcome are
      mostly based on the results of patients who underwent vaginal RT. More data are
      needed to be able to draw the same conclusions for abdominal RT. Fertility seems
      not to be decreased, but the risk for premature delivery is 2 to 3 times higher
      compared to women with an intact cervix. In locally advanced cervical tumors with
      a diameter larger than 2 cm, neoadjuvant chemotherapy followed by RT may be
      offered after explaining the experimental nature to the patient. In conclusion,
      RT is an oncologically safe technique in women with early invasive cancer. The
      rate of term pregnancies still needs improvement. Fertility-preserving treatment
      of women with tumors larger than 2 cm in diameter can be done by combining
      neoadjuvant chemotherapy and trachelectomy; however, experience is still limited.

PMID- 22398709
TI  - Advances in clinical research in gynecologic radiation oncology: an RTOG
      symposium.
AB  - There have been inexorable improvements in gynecologic radiation oncology through
      technologically advances, 3-dimensional imaging, and clinical research.
      Investment in these 3 critical areas has improved, and will continue to improve,
      the lives of patients with gynecologic cancer. Advanced technology delivery in
      gynecologic radiation oncology is challenging owing to the following: (1) setup
      difficulties, (2) managing considerable internal organ motion, and (3) responding
      to tumor volume reduction during treatment. Image guidance is a potential route
      to solve these problems and improve delivery to tumor and sparing organs at risk.
      Imaging with positron emission tomography-computed tomography and magnetic
      resonance imaging are contributing significantly to improved accuracy in
      diagnosis, treatment, and follow-up in cancer of the cervix. Functional imaging
      by exploiting tumor biology may improve prognosis and treatment. Clinical trials
      have been the greatest mechanism to improve and establish standards of care in
      women with vulvar, endometrial, and cervical cancer. There have been multiple
      technological advances and practice changing trials within the past several
      decades. Many important questions remain in optimizing care for women with
      gynecologic malignancies. The performance of clinical trials will be advanced
      with the use of consistent language (ie, similar staging system and criteria),
      eligibility criteria that fit the research question, end points that matter,
      adequate statistical power, complete follow-up, and prompt publication of mature
      results.

PMID- 22398710
TI  - Sexual function after intracavitary vaginal brachytherapy for early-stage
      endometrial carcinoma.
AB  - OBJECTIVE: To describe the effects of intracavitary brachytherapy (IVB) on sexual
      function and quality of life of women with early-stage endometrial cancer.
      METHODS: Women with International Federation of Gynecology and Obstetrics stage I
      to stage II endometrial cancer treated surgically with or without IVB were
      identified and mailed questionnaires. Quality of life and sexual function were
      measured using the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire Core 30 and the cervical cancer disease-specific
      module. Pertinent data from prior surgery and radiation treatments were
      abstracted retrospectively. Linear transformation of the survey subscale scores
      was conducted per European Organization for Research and Treatment of Cancer
      guidelines. RESULTS: Sixteen women in the IVB arm and 53 in the surgery-alone
      group completed the survey. Of the sexually active patients, 33% of the IVB
      patients and 42% of the surgery-alone patients felt their vagina was dry during
      sexual activity (P = 0.804) and 17% versus 20% felt their vagina was short (P =
      0.884). Seventeen percent of patients in the IVB group felt their vagina was
      tight compared to 29% in the surgery-alone group (P = 0.891) and 0% versus 14% of
      patients reported pain during intercourse (P = 0.808). There was no statistically
      significant difference in sexual/vaginal functioning, sexual worry, or sexual
      enjoyment between the 2 groups. CONCLUSIONS: Although both groups report vaginal
      changes that may affect sexual function, the patients treated with IVB reported
      similar outcomes on a sexual function questionnaire compared to patients treated
      with surgery alone.

PMID- 22398711
TI  - Correlation between FDG uptake by PET/CT and the expressions of glucose
      transporter type 1 and hexokinase II in cervical cancer.
AB  - BACKGROUND: The aim of this study was to explore the association between 2-deoxy
      2-F18-fluoro-D-glucose uptake and the expressions of glucose transporter type 1
      (GLUT-1) and hexokinase II (HK-II) in the lymph nodes of patients with cervical
      cancer. METHODS: This prospective study included 20 women with International
      Federation of Gynecology and Obstetrics stage IB to stage IIA cervical cancer who
      underwent positron emission tomography (PET)-computed tomography (CT) (PET/CT)
      before surgical treatment. In 333 dissected lymph nodes (LNs) obtained, we
      examined the size, tumor involvement, and expressions of GLUT-1 and HK-II. These
      characteristics were compared with PET/CT and pathological findings. RESULTS:
      Pathological analysis found that 21% (70) of the 333 surgically dissected LNs
      were metastatic. Positron emission tomography/CT detected metastasis with 22.8%
      sensitivity and 98.5% specificity. The levels of GLUT-1 and HK-II expression in
      false-positive LNs were higher than those in pathologically confirmed negative
      nodes (P = 0.015 and P = 0.001, respectively). In metastatic LNs, PET/CT-positive
      nodes were significantly different from PET/CT-negative nodes in mean size (P =
      0.043), tumor involvement (P = 0.008), and proportion of GLUT-1-positive tumor
      cells (P = 0.042). CONCLUSIONS: Our results indicate that overexpression of GLUT
      1 and HK-II may be related to 2-deoxy-2-F18-fluoro-D-glucose uptake in false
      positive tissues on PET/CT. In metastatic lymph nodes, the ability of PET/CT to
      detect cancer may depend on tumor involvement, lymph node size, and GLUT-1
      expression.

PMID- 22398712
TI  - Patterns of recurrence in endometrial cancer patients at risk of lymph node
      metastasis or recurrence according to extent of lymphadenectomy.
AB  - OBJECTIVE: The purpose of this study was to compare the patterns of recurrence in
      patients with risk of lymph node (LN) metastasis or recurrence according to the
      extent of lymphadenectomy (LND). METHODS: We selected 257 patients with risk of
      LN metastasis or recurrence who underwent definitive surgery as the first
      treatment between 1995 and 2009. These patients underwent hysterectomy, bilateral
      salpingo-oophorectomy, and systematic pelvic lymphadenectomy (PLND) with or
      without para-aortic lymphadenectomy (PALND). We identified patients with
      recurrence and evaluated the patterns of recurrence according to the type of LND.
      RESULTS: Among the 257 patients, 164 patients had systematic PLND only, and 93
      patients had PLND with PALND. Regarding LN metastasis in PLND+PALND group,
      approximately 9.7% patients had involvement of para-aortic nodes. Thirty-six
      (14%) of the 257 patients showed recurrence. The rate of extrapelvic recurrence
      was significantly higher in the PLND group compared with the PLND+PALND group
      (96.0% vs 36.4%, respectively; P < 0.001). Using multivariate analysis, extent of
      LND was significantly related to extrapelvic recurrence (P = 0.004). CONCLUSIONS:
      The incidence of extrapelvic recurrence was significantly higher in the PLND
      group than in the PLND+PALND group, which suggests that PALND decreases the risk
      of extrapelvic recurrence.

PMID- 22398713
TI  - Elevated temperature applied during gonadal transformation leads to male bias in
      zebrafish (Danio rerio).
AB  - Temperature effects on sex determination or differentiation exist in many fish
      species, with high temperatures predominantly producing more males. The present
      study aimed at elucidating the genetic background of temperature effects on sex
      differentiation in zebrafish. Experimental fish were generated by matings between
      4 or 6 golden females and a normal or a mitotic gynogenetic male, respectively.
      All the larvae were reared at 28.5 degrees C until they were divided into 3
      groups per full-sib family, a control group raised at 28.5 degrees C and 2
      treatment groups reared at 35 degrees C from 20 to 30 dpf or 25 to 35 dpf,
      respectively. Backcross progenies, reared at 28.5 degrees C, were derived from F1
      temperature-treated sons (35 degrees C, 25-35 dpf) that were sired by a mitotic
      gynogenetic male and their corresponding mothers. No significant differences were
      observed regarding the survival rate between the control and treatment groups.
      Significant differences in the phenotypic male proportions from the controls were
      observed in groups treated at 35 degrees C. The sex ratio in zebrafish was
      influenced by the male spawner, the female spawner, and a significant interaction
      of genotype by temperature. Backcross experiments point to a continuum of major
      genetic, minor genetic, and environmental factors in the expression of the
      phenotypic sex in zebrafish.

PMID- 22398714
TI  - Cytomegalovirus (CMV) seroprevalence in pregnant women, bone marrow donors and
      adolescents in Germany, 1996-2010.
AB  - In Germany, studies on the IgG seroprevalence in pregnancy and in women of
      childbearing age are rare. Therefore, we retrospectively evaluated the CMV IgG
      seropositive rate in 40,324 pregnant women as well as in 31,093 female and male
      bone marrow donors over 15 consecutive years (1996-2010). Furthermore, the result
      of a study conducted in 1999 investigating 1,305 healthy adolescents with known
      ethnicity was included. The overall CMV IgG seroprevalence in pregnant women (15
      50 years) was 42.3%. Age-dependent analysis revealed a significantly higher
      seropositive rate (55.6%) in young women (15-25 years) than in those aged 26-40
      years (37-42%) and in women older than 40 years (48.3%). Over the study period of
      15 years, the rate of seroprevalence in pregnant women declined significantly
      (chi(2) test < 0.01) from 44.3% in the first interval period (1996-2000), to
      42.8% (2001-2005) and to 40.9% (2006-2010). The most influencing factor on CMV
      seropositivity appeared to be the socioeconomic status (SES), which we
      characterized by type of health insurance: Seroprevalence in women with low,
      middle and upper SES was 91.8, 46.9 and 33.7%, respectively. Female bone marrow
      donors of childbearing age (15-45 years) showed a significantly higher
      seropositive rate of 36.5% than age-matched male donors (28.6%). In adolescents
      aged 13-16 years, no gender-specific differences were recognized. Concerning
      ethnicity, youngsters with German descent had a significantly lower
      seroprevalence (29.9%) than those with non-German descent (67.4%).

PMID- 22398715
TI  - Immunosuppressive function of mesenchymal stem cells from human umbilical cord
      matrix in immune thrombocytopenia patients.
AB  - Human umbilical cord matrix/Wharton's jelly (hUC)-derived mesenchymal stem cells
      (MSC) have been shown to have marked therapeutic effects in a number of
      inflammatory diseases and autoimmune diseases in humans based on their potential
      for immunosuppression and their low immunogenicity. Currently, no data are
      available on the effectiveness of UC-MSC transplantation in immune
      thrombocytopenia (ITP) patients. It was the objective of this study to assess the
      effect of allogeneic UC-MSCs on ITP patients in vitro and in vivo. Peripheral
      blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BM-MNCs) from
      ITP patients and healthy controls were co-cultured with UC-MSCs for three days
      and seven days, respectively. Flow cytometry and ELISA were applied to assess the
      various parameters. In PBMCs from ITP patients, the proliferation of autoreactive
      T, B lymphocytes and destruction of autologous platelets were dramatically
      suppressed by UC-MSCs. UC-MSCs not only suppressed co-stimulatory molecules CD80,
      CD40L and FasL expression but also in shifting Th1/Th2/Treg cytokines profile in
      ITP patients. UC-MSCs obviously reversed the dysfunctions of megakaryocytes by
      promoting platelet production and decreasing the number of living megakaryocytes
      as well as early apoptosis. In addition, the level of thrombopoietin was
      increased significantly. Our clinical study showed that UC-MSCs play a role in
      alleviating refractory ITP by increasing platelet numbers. These findings
      suggested that UC-MSCs transplantation might be a potential therapy for ITP.

PMID- 22398716
TI  - Chain confinement promotes beta-phase formation in polyfluorene-based
      photoluminescent ionogels.
AB  - The synthesis of photoluminescent conjugated polymer silica ionogels using sol
      gel chemistry is described. Cooperative self-assembly of an ionic liquid, the
      silica precursor and poly(9,9-dioctylfluorene) (PFO) via hydrogen bonding and pi
      stacking interactions drives formation of the PFO beta-phase.

PMID- 22398717
TI  - Not all inflammatory markers are linked to kidney function: results from a
      population-based study.
AB  - BACKGROUND: Several studies have reported increased levels of inflammatory
      biomarkers in chronic kidney disease (CKD), but data from the general population
      are sparse. In this study, we assessed levels of the inflammatory markers C
      reactive protein (hsCRP), tumor necrosis factor alpha (TNF-alpha), interleukin
      (IL)-1beta and IL-6 across all ranges of renal function. METHODS: We conducted a
      cross-sectional study in a random sample of 6,184 Caucasian subjects aged 35-75
      years in Lausanne, Switzerland. Serum levels of hsCRP, TNF-alpha, IL-6, and IL
      1beta were measured in 6,067 participants (98.1%); serum creatinine-based
      estimated glomerular filtration rate (eGFR(creat), CKD-EPI formula) was used to
      assess renal function, and albumin/creatinine ratio on spot morning urine to
      assess microalbuminuria (MAU). RESULTS: Higher serum levels of IL-6, TNF-alpha
      and hsCRP and lower levels of IL-1beta were associated with a lower renal
      function, CKD (eGFR(creat) <60 ml/min/1.73 m(2); n = 283), and MAU (n = 583). In
      multivariate linear regression analysis adjusted for age, sex, hypertension,
      smoking, diabetes, body mass index, lipids, antihypertensive and hypolipemic
      therapy, only log-transformed TNF-alpha remained independently associated with
      lower renal function (beta -0.54 +/-0.19). In multivariate logistic regression
      analysis, higher TNF-alpha levels were associated with CKD (OR 1.17; 95% CI 1.01
      1.35), whereas higher levels of IL-6 (OR 1.09; 95% CI 1.02-1.16) and hsCRP (OR
      1.21; 95% CI 1.10-1.32) were associated with MAU. CONCLUSION: We did not confirm
      a significant association between renal function and IL-6, IL-1beta and hsCRP in
      the general population. However, our results demonstrate a significant
      association between TNF-alpha and renal function, suggesting a potential link
      between inflammation and the development of CKD. These data also confirm the
      association between MAU and inflammation.

PMID- 22398718
TI  - Associated expression of alpha2,3sialylated type 2 chain structures with lymph
      node metastasis in distal colorectal cancer.
AB  - PURPOSE: One of the typical modifications on the surface of cancer cells is
      sialylation of terminal carbohydrates. The expression of several types of
      sialylation of glycoconjugates was investigated in colorectal cancer. METHODS:
      The cancer tissue specimens obtained from 65 colorectal cancer patients were
      stained with sialic acid-binding lectins from Maackia amurensis (MAM), Sambucus
      sieboldiana (SSA), Maackia amurensis agglutinin (MAA) and monoclonal antibodies,
      and compared with their clinicopathological features. RESULTS: Cancer tissue
      specimens from 44.6% of patients had positive staining with MAM, which recognized
      alpha2,3sialylated type 2 chain (NeuAcalpha2,3Galbeta1,4GlcNAcbetaR) structures,
      but normal colorectal mucosa showed only weak staining with MAM was observed.
      More lymph node metastases and lymphatic invasion were seen in patients with
      positive staining with MAM (P < 0.01), while not with other lectins or antibodies
      that recognized sialylated glycoconjugates or sialyl Lewis-related antigens. The
      five-year survival rate of patients with MAM-positive staining was significantly
      lower than that with MAM-negative staining when including T0-1 cases, but there
      was no difference in cases with T2-4. There was no difference in the patients'
      survival rates when the tissues were stained with MAA, SSA or PNA lectins.
      CONCLUSION: alpha2,3Sialylated type 2 chain structures were predominantly
      expressed in colorectal tissues associated with the malignant transformation, in
      particular, with lymphatic spread of distal colorectal adenocarcinomas.

PMID- 22398719
TI  - Pathological complete response of locally advanced gastric cancer after four
      courses of neoadjuvant chemotherapy with paclitaxel plus cisplatin: report of a
      case.
AB  - We report a case of advanced gastric carcinoma treated successfully by four
      courses of neoadjuvant chemotherapy (NAC) with paclitaxel and cisplatin. The
      patient was a 43-year-old man with advanced gastric cancer, clinically diagnosed
      as P0H0M0CY0T3N2, which had invaded the upper body of the stomach and esophagus.
      He was entered into a clinical trial and received the following NAC regimen:
      paclitaxel 80 mg/m(2), and cisplatin 25 mg/m(2), on days 1, 8, and 15, followed
      by a rest on day 22, as one course. The lymph nodes had reduced in size to 59%
      after two courses and to 40% after four courses, with no sign of severe toxicity.
      Subsequently, he underwent D2 total gastrectomy with pancreatico-splenectomy. On
      microscopic examinations, no tumor cells were detected in the ulcer scar of the
      resected stomach or the regional lymph nodes. Thus, we discuss the potential of
      long-term NAC, especially for responders to two initial courses.

PMID- 22398721
TI  - A VE-cadherin-PAR3-alpha-catenin complex regulates the Golgi localization and
      activity of cytosolic phospholipase A(2)alpha in endothelial cells.
AB  - Phospholipase A(2) enzymes hydrolyze phospholipids to liberate arachidonic acid
      for the biosynthesis of prostaglandins and leukotrienes. In the vascular
      endothelium, group IV phospholipase A(2)alpha (cPLA(2)alpha) enzyme activity is
      regulated by reversible association with the Golgi apparatus. Here we provide
      evidence for a plasma membrane cell adhesion complex that regulates endothelial
      cell confluence and simultaneously controls cPLA(2)alpha localization and
      enzymatic activity. Confluent endothelial cells display pronounced accumulation
      of vascular endothelial cadherin (VE-cadherin) at cell-cell junctions, and
      mechanical wounding of the monolayer stimulates VE-cadherin complex disassembly
      and cPLA(2)alpha release from the Golgi apparatus. VE-cadherin depletion inhibits
      both recruitment of cPLA(2)alpha to the Golgi and formation of tubules by
      endothelial cells. Perturbing VE-cadherin and increasing the soluble cPLA(2)alpha
      fraction also stimulated arachidonic acid and prostaglandin production. Of
      importance, reverse genetics shows that alpha-catenin and delta-catenin, but not
      beta-catenin, regulates cPLA(2)alpha Golgi localization linked to cell
      confluence. Furthermore, cPLA(2)alpha Golgi localization also required
      partitioning defective protein 3 (PAR3) and annexin A1. Disruption of F-actin
      internalizes VE-cadherin and releases cPLA(2)alpha from the adhesion complex and
      Golgi apparatus. Finally, depletion of either PAR3 or alpha-catenin promotes
      cPLA(2)alpha-dependent endothelial tubule formation. Thus a VE-cadherin-PAR3
      alpha-catenin adhesion complex regulates cPLA(2)alpha recruitment to the Golgi
      apparatus, with functional consequences for vascular physiology.

PMID- 22398720
TI  - The apoptotic engulfment protein Ced-6 participates in clathrin-mediated yolk
      uptake in Drosophila egg chambers.
AB  - Clathrin-mediated endocytosis and phagocytosis are both selective surface
      internalization processes but have little known mechanistic similarity or
      interdependence. Here we show that the phosphotyrosine-binding (PTB) domain
      protein Ced-6, a well-established phagocytosis component that operates as a
      transducer of so-called "eat-me" signals during engulfment of apoptotic cells and
      microorganisms, is expressed in the female Drosophila germline and that Ced-6
      expression correlates with ovarian follicle development. Ced-6 exhibits all the
      known biochemical properties of a clathrin-associated sorting protein, yet ced-6
      null flies are semifertile despite massive accumulation of soluble yolk
      precursors in the hemolymph. This is because redundant sorting signals within the
      cytosolic domain of the Drosophila vitellogenin receptor Yolkless, a low density
      lipoprotein receptor superfamily member, occur; a functional atypical dileucine
      signal binds to the endocytic AP-2 clathrin adaptor directly. Nonetheless, the
      Ced-6 PTB domain specifically recognizes the noncanonical Yolkless FXNPXA sorting
      sequence and in HeLa cells promotes the rapid, clathrin-dependent uptake of a
      Yolkless chimera lacking the distal dileucine signal. Ced-6 thus operates in vivo
      as a clathrin adaptor. Because the human Ced-6 orthologue GULP similarly binds to
      clathrin machinery, localizes to cell surface clathrin-coated structures, and is
      enriched in placental clathrin-coated vesicles, new possibilities for Ced-6/Gulp
      operation during phagocytosis must be considered.

PMID- 22398722
TI  - A three-component mechanism for fibroblast migration with a contractile cell body
      that couples a myosin II-independent propulsive anterior to a myosin II-dependent
      resistive tail.
AB  - To understand the mechanism of cell migration, we cultured fibroblasts on
      micropatterned tracks to induce persistent migration with a highly elongated
      morphology and well-defined polarity, which allows microfluidic pharmacological
      manipulations of regional functions. The function of myosin II was probed by
      applying inhibitors either globally or locally. Of interest, although global
      inhibition of myosin II inhibited tail retraction and caused dramatic elongation
      of the posterior region, localized inhibition of the cell body inhibited nuclear
      translocation and caused elongation of the anterior region. In addition, local
      application of cytochalasin D at the tip inhibited frontal extension without
      inhibiting forward movement of the cell nucleus, whereas local treatment
      posterior to the nucleus caused reversal of nuclear movement. Imaging of cortical
      dynamics indicated that the region around the nucleus is a distinct compression
      zone where activities of anterior and posterior regions converge. These
      observations suggest a three-component model of cell migration in which a
      contractile middle section is responsible for the movement of a bulky cell body
      and the detachment/retraction of a resistive tail, thereby allowing these regions
      to undergo coordinated movement with a moving anterior region that carries little
      load.

PMID- 22398723
TI  - The RNA-binding protein QKI5 is a direct target of C/EBPalpha and delays
      macrophage differentiation.
AB  - Differentiated macrophages are essential for the innate immune system; however,
      the molecular mechanisms underlying the generation of macrophages remain largely
      unknown. Here we show that the RNA-binding protein QKI, mainly QKI-5, is
      transcriptionally activated in the early differentiated monocytic progenitors
      when CCAAT/enhancer-binding protein (C/EBP) alpha is expressed. The forced
      expression of C/EBPalpha increases the endogenous expression of QKI. Chromatin
      immunoprecipitation analysis and reporter assays further confirm that C/EBPalpha
      activates the transcription of QKI, primarily by binding to the distal C/EBPalpha
      binding site. Blocking the induction of QKI using RNA interference enhances the
      expression of endogenous CSF1R and facilitates macrophage differentiation.
      Further study of the mechanism reveals that QKI-5 facilitates the degradation of
      CSF1R mRNA by interacting with the distal QRE in the 3' untranslated region. In
      summary, we show that in committed macrophage progenitors, C/EBPalpha-activated
      QKI-5 negatively regulates macrophage differentiation by down-regulating CSF1R
      expression, forming a negative feedback loop during macrophage differentiation.

PMID- 22398724
TI  - Localized accumulation of tubulin during semi-open mitosis in the Caenorhabditis
      elegans embryo.
AB  - The assembly of microtubules inside the cell is controlled both spatially and
      temporally. During mitosis, microtubule assembly must be activated locally at the
      nascent spindle region for mitotic spindle assembly to occur efficiently. In this
      paper, we report that mitotic spindle components, such as free tubulin subunits,
      accumulated in the nascent spindle region, independent of spindle formation in
      the Caenorhabditis elegans embryo. This accumulation coincided with nuclear
      envelope permeabilization, suggesting that permeabilization might trigger the
      accumulation. When permeabilization was induced earlier by knockdown of lamin,
      tubulin also accumulated earlier. The boundaries of the region of accumulation
      coincided with the remnant nuclear envelope, which remains after nuclear envelope
      breakdown in cells that undergo semi-open mitosis, such as those of C. elegans.
      Ran, a small GTPase protein, was required for tubulin accumulation. Fluorescence
      recovery after photobleaching analysis revealed that the accumulation was
      accompanied by an increase in the immobile fraction of free tubulin inside the
      remnant nuclear envelope. We propose that this newly identified mechanism of
      accumulation of free tubulin-and probably of other molecules-at the nascent
      spindle region contributes to efficient assembly of the mitotic spindle in the C.
      elegans embryo.

PMID- 22398725
TI  - Molecular motor function in axonal transport in vivo probed by genetic and
      computational analysis in Drosophila.
AB  - Bidirectional axonal transport driven by kinesin and dynein along microtubules is
      critical to neuronal viability and function. To evaluate axonal transport
      mechanisms, we developed a high-resolution imaging system to track the movement
      of amyloid precursor protein (APP) vesicles in Drosophila segmental nerve axons.
      Computational analyses of a large number of moving vesicles in defined genetic
      backgrounds with partial reduction or overexpression of motor proteins enabled us
      to test with high precision existing and new models of motor activity and
      coordination in vivo. We discovered several previously unknown features of
      vesicle movement, including a surprising dependence of anterograde APP vesicle
      movement velocity on the amount of kinesin-1. This finding is largely
      incompatible with the biophysical properties of kinesin-1 derived from in vitro
      analyses. Our data also suggest kinesin-1 and cytoplasmic dynein motors assemble
      in stable mixtures on APP vesicles and their direction and velocity are
      controlled at least in part by dynein intermediate chain.

PMID- 22398726
TI  - PDK1 in apical signaling endosomes participates in the rescue of the polarity
      complex atypical PKC by intermediate filaments in intestinal epithelia.
AB  - Phosphorylation of the activation domain of protein kinase C (PKC) isoforms is
      essential to start a conformational change that results in an active catalytic
      domain. This activation is necessary not only for newly synthesized molecules,
      but also for kinase molecules that become dephosphorylated and need to be
      refolded and rephosphorylated. This "rescue" mechanism is responsible for the
      maintenance of the steady-state levels of atypical PKC (aPKC [PKCiota/lambda and
      zeta]) and is blocked in inflammation. Although there is consensus that
      phosphoinositide-dependent protein kinase 1 (PDK1) is the activating kinase for
      newly synthesized molecules, it is unclear what kinase performs that function
      during the rescue and where the rescue takes place. To identify the activating
      kinase during the rescue mechanism, we inhibited protein synthesis and analyzed
      the stability of the remaining aPKC pool. PDK1 knockdown and two different PDK1
      inhibitors-BX-912 and a specific pseudosubstrate peptide-destabilized PKCiota.
      PDK1 coimmunoprecipitated with PKCiota in cells without protein synthesis,
      confirming that the interaction is direct. In addition, we showed that PDK1 aids
      the rescue of aPKC in in vitro rephosphorylation assays using immunodepletion and
      rescue with recombinant protein. Surprisingly, we found that in Caco-2 epithelial
      cells and intestinal crypt enterocytes PDK1 distributes to an apical membrane
      compartment comprising plasma membrane and apical endosomes, which, in turn, are
      in close contact with intermediate filaments. PDK1 comigrated with the Rab11
      compartment and, to some extent, with the transferrin compartment in sucrose
      gradients. PDK1, pT555-aPKC, and pAkt were dependent on dynamin activity. These
      results highlight a novel signaling function of apical endosomes in polarized
      cells.

PMID- 22398727
TI  - Axonal and dendritic synaptotagmin isoforms revealed by a pHluorin-syt functional
      screen.
AB  - The synaptotagmins (syts) are a family of molecules that regulate membrane
      fusion. There are 17 mammalian syt isoforms, most of which are expressed in the
      brain. However, little is known regarding the subcellular location and function
      of the majority of these syts in neurons, largely due to a lack of isoform
      specific antibodies. Here we generated pHluorin-syt constructs harboring a
      luminal domain pH sensor, which reports localization, pH of organelles to which
      syts are targeted, and the kinetics and sites of exocytosis and endocytosis. Of
      interest, only syt-1 and 2 are targeted to synaptic vesicles, whereas other
      isoforms selectively recycle in dendrites (syt-3 and 11), axons (syt-5, 7, 10,
      and 17), or both axons and dendrites (syt-4, 6, 9, and 12), where they undergo
      exocytosis and endocytosis with distinctive kinetics. Hence most syt isoforms
      localize to distinct secretory organelles in both axons and dendrites and may
      regulate neuropeptide/neurotrophin release to modulate neuronal function.

PMID- 22398728
TI  - A technique for mapping cortical areas associated with speech arrest.
AB  - BACKGROUND: Awake craniotomy with cortical stimulation is the standard for
      language mapping in patients with tumors near or within the language cortex.
      Reliable identification of the speech cortex is difficult, however, and
      adjunctive pre- and intraoperative techniques have inconsistent reliability.
      OBJECTIVES: We describe a technique based on direct cortical stimulation which
      localizes speech areas by correlating vocal cord activation in the anesthetized
      patient with speech arrest in the awake patient. METHODS: Direct cortical
      stimulation is applied to the patient and the vocal cords are visualized by
      fiberoptic endoscopy. The cortical site that produces vocal cord activation is
      identified. Once the patient is awakened, cortical stimulation is repeated and
      sites that produce speech arrest are identified. RESULTS: We have performed this
      technique in 3 patients and have consistently correlated vocal cord activation
      with speech arrest in all patients. These areas of activation also correlate with
      areas of functional MRI BOLD activation obtained from the expressive language
      paradigms. CONCLUSIONS: Colocalization of the site of vocal cord activation in
      the asleep patient to the site of speech arrest in the awake patient represents
      an adjunct for defining speech areas. This technique is useful for patients
      unable to tolerate awake craniotomy.

PMID- 22398729
TI  - Drug allergy in hospitalized patients: the contribution of allergy consultation
      and a structured questionnaire.
AB  - BACKGROUND: Hospitalized patients with an alleged history of drug allergy pose
      medical and economic concerns when selecting medications for treatment, possibly
      leading to deviations from standards of care and the use of expensive agents.
      Accurate history taking and clear documentation of drug allergy are essential for
      preventing subsequent administration of the offending drug and overdiagnosis of
      drug allergy. We aimed to evaluate drug allergy-related history taking by
      internists compared to allergists and to prospectively assess the effect of a
      simple, structured questionnaire on the accuracy of drug allergy diagnosis.
      METHODS: Consenting patients with an alleged drug allergy who were able to give a
      coherent history were recruited from two internal medicine wards. In both wards,
      the internists' drug allergy diagnosis was initially compared to that of the
      allergists. In the second part, in the intervention ward, after the same
      procedure, the internists completed the structured questionnaire. Their
      diagnostic conclusions with and without the questionnaire were compared. RESULTS:
      202 patients labeled with a medication allergy were enrolled. In the control and
      intervention wards, 54 and 58% of the patients, respectively, labeled by the
      internists as allergic, were found not to be allergic by the allergist. In the
      intervention ward, after using the questionnaire, the percentage of patients
      tagged by the internists as allergic dropped initially by 31% and finally by 59%.
      CONCLUSIONS: Discrepancies between drug allergy diagnosis of internists and
      allergists are common. Allergist consultation or use of a simple structured
      questionnaire may be beneficial for accurate diagnosis of drug allergies.

PMID- 22398730
TI  - Neuroinflammation and common mechanism in Alzheimer's disease and prion
      amyloidosis: amyloid-associated proteins, neuroinflammation and neurofibrillary
      degeneration.
AB  - BACKGROUND: In cases with a long (>1 year) clinical duration of prion disease,
      the prion protein can form amyloid deposits. These cases do not show accumulation
      of 4-kDa beta-amyloid, which is observed in amyloid deposits in Alzheimer's
      disease (AD). In AD, amyloid is associated with inflammation and neurofibrillary
      degeneration, and it is elusive whether prion amyloid is associated with these
      changes as well. OBJECTIVES: The presence of inflammation and neurofibrillary
      degeneration was evaluated in prion amyloidosis. MATERIAL AND METHODS: Cortical
      areas of variant Creutzfeldt-Jakob disease (CJD; n = 3), young sporadic CJD (n =
      4), different Gerstmann-Straussler-Scheinker's disease patients (n = 5) and AD
      cases (n = 5) were examined using immunohistochemistry and specific stainings for
      amyloid. RESULTS: In both AD and prion disease cases, which were negative for 4
      kDa beta-amyloid, parenchymal and vascular amyloid deposits were positive for
      amyloid-associated proteins such as complement protein and were associated with
      microglia clusters. Tau and ubiquitin were found near prion plaques in some of
      the Gerstmann-Straussler-Scheinker's disease and sporadic CJD cases and also near
      vascular prion amyloid deposits. In variant CJD cases, occasionally, microglia
      clustering was found in plaques but no ubiquitin or complement proteins and
      hardly tau protein. CONCLUSIONS: In both AD and prion disease amyloid formation,
      irrespective of the protein involved, there seems to be a neuroinflammatory
      response with secondary neurofibrillary degeneration.

PMID- 22398731
TI  - Highlights in T-cell lymphoma from the 2011 American Society of Hematology Annual
      Meeting and Exposition.

PMID- 22398732
TI  - Ultrasonographic assessment of flexor tendon mobilization: effect of different
      protocols on tendon excursion.
AB  - BACKGROUND: Different mobilization protocols have been proposed for
      rehabilitation after hand flexor tendon repair to provide tendon excursion
      sufficient to prevent adhesions. Several cadaver studies have shown that the
      position of the neighboring fingers influences tendon excursions of the injured
      finger. We hypothesized that the positions of adjacent fingers influence the long
      finger flexor digitorum profundus tendon excursion, measured both absolutely and
      relative to the surrounding tissue of the tendon. METHODS: Long finger flexor
      digitorum profundus tendon excursions and surrounding tissue movement were
      measured in zone V in eleven healthy subjects during three different
      rehabilitation protocols and two experimental models: (1) an active four-finger
      mobilization protocol, (2) a passive four-finger mobilization protocol, (3) a
      modified Kleinert mobilization protocol, (4) an experimental modified Kleinert
      flexion mobilization model, and (5) an experimental modified Kleinert extension
      mobilization model. Tendon excursions were measured with use of a frame-to-frame
      analysis of high-resolution ultrasound images. RESULTS: The median absolute long
      finger flexor digitorum profundus tendon excursions were 23.4, 17.8, 10.0, 13.9,
      and 7.6 mm for the active four-finger mobilization protocol, the passive four
      finger mobilization protocol, the modified Kleinert mobilization protocol, the
      experimental modified Kleinert flexion mobilization model, and the experimental
      modified Kleinert extension mobilization model, respectively, and these
      differences were all significant (p <= 0.041). The corresponding relative flexor
      digitorum profundus tendon excursions were 11.2, 8.5, 7.2, 10.4, and 5.6 mm.
      Active four-finger mobilization protocol excursions were significantly (p =
      0.013) greater than passive four-finger mobilization protocol excursions but were
      not significantly greater than experimental modified Kleinert flexion
      mobilization model excursions (p =0.213). CONCLUSIONS: The present study
      demonstrated large and significant differences among the different rehabilitation
      protocols and experimental models in terms of absolute and relative tendon
      displacement. More importantly, the present study clearly demonstrated the
      influence of the position of the adjacent fingers on the flexor tendon
      displacement of the finger that is mobilized.

PMID- 22398734
TI  - Return of motor function after segmental nerve loss in a rat model: comparison of
      autogenous nerve graft, collagen conduit, and processed allograft (AxoGen).
AB  - BACKGROUND: An effective alternative to nerve autograft is needed to minimize
      morbidity and solve limited-availability issues. We hypothesized that the use of
      processed allografts and collagen conduits would allow recovery of motor function
      that is equivalent to that seen after the use of autografts. METHODS: Sixty-five
      Lewis rats were divided into three experimental groups. In each group, a
      unilateral 10-mm sciatic nerve defect was repaired with nerve autograft,
      allograft treated by AxoGen Laboratories, or a 2.0-mm-inner-diameter collagen
      conduit. The animals were studied at twelve and sixteen weeks postoperatively.
      Evaluation included bilateral measurement of the tibialis anterior muscle force
      and muscle weight, electrophysiology, assessment of ankle contracture, and
      peroneal nerve histomorphometry. Muscle force was measured with use of our
      previously described and validated method. Results were expressed as a percentage
      of the values on the contralateral side. Two-way analysis of variance (ANOVA)
      corrected by the Ryan-Einot-Gabriel-Welsch multiple range test was used for
      statistical investigation (alpha = 0.05). RESULTS: At twelve weeks, the mean
      muscle force (and standard deviation), as compared with that on the contralateral
      (control) side, was 45.2% +/- 15.0% in the autograft group, 43.4% +/- 18.0% in
      the allograft group, and 7.0% +/- 9.2% in the collagen group. After sixteen
      weeks, the recovered muscle force was 65.5% +/- 14.1% in the autograft group,
      36.3% +/- 15.7% in the allograft group, and 12.1% +/- 16.0% in the collagen
      group. Autograft was statistically superior to allograft and the collagen conduit
      at sixteen weeks with regard to all parameters except histomorphometric
      characteristics (p < 0.05). The collagen-group results were inferior. All
      autograft-group outcomes improved from twelve to sixteen weeks, with the increase
      in muscle force being significant. CONCLUSIONS: The use of autograft resulted in
      better motor recovery than did the use of allograft or a collagen conduit for a
      short nerve gap in rats. A longer evaluation time of sixteen weeks after
      segmental nerve injuries in rats would be beneficial as more substantial muscle
      recovery was seen at that time.

PMID- 22398733
TI  - The prevalence, rate of progression, and treatment of elbow flexion contracture
      in children with brachial plexus birth palsy.
AB  - BACKGROUND: Elbow flexion contracture is a well-known complication of brachial
      plexus birth palsy that adversely affects upper-extremity function. The
      prevalence, risk factors, and rate of progression of elbow flexion contracture
      associated with brachial plexus birth palsy have not been established, and the
      effectiveness of nonoperative treatment involving nighttime splinting or serial
      casting has not been well studied. METHODS: The medical records of 319 patients
      with brachial plexus birth palsy who had been seen at our institution between
      1992 and 2009 were retrospectively reviewed to identify patients with an elbow
      flexion contracture (>=10 degrees ). The chi-square test for trend and the Kaplan
      Meier estimator were used to evaluate risk factors for contracture, including
      age, sex, and the extent of brachial plexus involvement. Longitudinal models were
      used to estimate the rate of contracture progression and the effectiveness of
      nonoperative treatment. RESULTS: An elbow flexion contracture was present in 48%
      (152) of the patients with brachial plexus birth palsy. The median age of onset
      was 5.1 years (range, 0.25 to 14.8 years). The contracture was >=30 degrees  in
      36% (fifty-four) of these 152 patients and was accompanied by a documented radial
      head dislocation in 6% (nine). The prevalence of contracture increased with
      increasing age (p < 0.001) but was not significantly associated with sex or with
      the extent of brachial plexus involvement. The magnitude of the contracture
      increased by 4.4% per year before treatment (p < 0.01). The magnitude of the
      contracture decreased by 31% when casting was performed (p < 0.01) but thereafter
      increased again at the same rate of 4.4% per year. The magnitude of the
      contracture did not improve when splinting was performed but the rate of increase
      thereafter decreased to <0.1% per year (p = 0.04). CONCLUSIONS: The prevalence of
      elbow flexion contracture in children with brachial plexus birth palsy may be
      greater than clinicians perceive. The prevalence increased with patient age but
      was not significantly affected by sex or by the extent of brachial plexus
      involvement. Serial casting may initially improve severe contractures, whereas
      nighttime splinting may prevent further progression of milder contractures.

PMID- 22398735
TI  - The rate of contralateral proximal femoral fracture following closed reduction
      and percutaneous pinning compared with arthroplasty for the treatment of femoral
      neck fractures.
AB  - BACKGROUND: As the population ages, the number of proximal femoral fractures seen
      each year is expected to increase. Subsequent contralateral hip fractures have
      been reported to occur in as many as 11.8% of patients after surgical fixation of
      the initial fracture, but it is unknown if this rate is similar among patients
      managed with different surgical procedures. METHODS: A retrospective comparative
      study was performed at a single institution at which electronic medical records
      and digital radiographs were reviewed for 1177 patients who underwent closed
      reduction and percutaneous pinning or arthroplasty for the treatment of a
      proximal femoral fracture. For the primary outcome of subsequent fracture,
      logistic regression analysis was applied. RESULTS: Four hundred and ninety-five
      patients were managed with closed reduction and percutaneous pinning, and 682
      were managed with arthroplasty. Patients who underwent closed reduction and
      percutaneous pinning were two times more likely to have a subsequent
      contralateral femoral fracture in comparison with those who underwent
      arthroplasty, with contralateral fracture rates of 10.10% for the closed
      reduction and percutaneous pinning group and 5.57% for the arthroplasty group (p
      = 0.0035). CONCLUSIONS: Patients undergoing closed reduction and percutaneous
      pinning as the initial treatment for a hip fracture had an increased risk of a
      subsequent contralateral hip fracture in comparison with those undergoing
      arthroplasty, after controlling for patient characteristics.

PMID- 22398736
TI  - Ten-year follow-up of a rotating-platform, posterior-stabilized total knee
      arthroplasty.
AB  - BACKGROUND: The rotating-platform, posterior-stabilized knee was designed to
      decrease polyethylene wear and to address challenges associated with Low Contact
      Stress mobile-bearing knees. The purpose of the present prospective study was to
      investigate the long-term clinical and radiographic results and the survival rate
      for this implant. METHODS: From January 2000 to October 2001, 117 consecutive
      patients (138 knees) underwent rotating-platform posterior-stabilized total knee
      arthroplasty with cement. All patients were followed prospectively. At a mean of
      10 +/- 0.4 years (range, 9.5 to eleven years) of follow-up, twenty patients had
      died and eight had been lost to follow-up, leaving eighty-nine patients (106
      knees) for analysis. RESULTS: A good to excellent result according to the Knee
      Society pain score, which improved from an average of 44 to 94 points, was
      achieved in 96% (eighty-five) of the eighty-nine patients in the final cohort.
      The mean knee motion improved from 111 degrees  to 119 degrees . The prevalence
      of postoperative pain was 14%. The prevalence of asymptomatic crepitation was
      9.4%, and the prevalence of painful crepitation requiring scar excision was 3.8%.
      Radiographic analysis revealed no malalignment, aseptic loosening, or osteolysis.
      There were three revisions: one for the treatment of infection and two for the
      treatment of traumatic supracondylar fractures. Kaplan-Meier analysis revealed
      that the ten-year survival rate was 100% with revision due to mechanical failure
      as the end point, 97.7% with revision for any reason as the end point, and 95%
      with any reoperation as the end point. CONCLUSIONS: The ten-year follow-up of the
      rotating-platform, posterior-stabilized total knee arthroplasty demonstrated
      excellent clinical results and survival rates with no failures due to osteolysis
      or loosening.

PMID- 22398737
TI  - Mortality and morbidity in dialysis-dependent patients undergoing spinal surgery:
      analysis of a national administrative database in Japan.
AB  - BACKGROUND: The impact of dialysis dependence on perioperative risks following
      spinal surgery is not fully understood. The purposes of the present study were to
      determine the perioperative risks in dialysis-dependent patients treated with
      spinal surgery and to examine whether the presence of destructive
      spondyloarthropathy further increases perioperative risks. METHODS: We examined
      abstracted data from the Diagnosis Procedure Combination database in a
      retrospective analysis of a nationally representative inpatient database. The
      survey of the database is conducted annually for a six-month period between July
      1 and December 31. The data from 2007 and 2008 were used for this study. We
      included all patients who had undergone any combination of laminectomy,
      laminoplasty, discectomy, and/or spinal arthrodesis. For analysis, dialysis
      dependent patients were further classified into subgroups with or without
      destructive spondyloarthropathy. RESULTS: We identified 51,648 eligible patients
      (30,743 men and 20,905 women; mean age, sixty-two years), including 869 (1.7%)
      who were dialysis-dependent. Of the latter, ninety-five had destructive
      spondyloarthropathy. Overall in-hospital mortality was 0.41%. Dialysis-dependent
      patients had a significantly higher in-hospital mortality rate than non-dialysis
      dependent patients. After adjustment, dialysis-dependent patients remained at a
      tenfold higher risk for in-hospital death. Dialysis-dependent patients were also
      at significantly greater risk for postoperative major complications. The rate of
      complications in dialysis-dependent patients with destructive spondyloarthropathy
      was 65% higher than that in those without destructive spondyloarthropathy, but
      this difference did not reach significance. CONCLUSIONS: Dialysis-dependent
      patients had a tenfold higher risk of in-hospital death than did non-dialysis
      dependent patients. Dialysis-dependent patients were also more likely to have
      major complications such as cardiac events, sepsis, and respiratory
      complications. Our data also indicate that the presence of destructive
      spondyloarthropathy is associated with a higher rate of postoperative
      complications in dialysis-dependent patients.

PMID- 22398738
TI  - Postoperative complications of posterior ankle and hindfoot arthroscopy.
AB  - BACKGROUND: Posterior ankle and hindfoot arthroscopy, performed with use of
      posteromedial and posterolateral portals with the patient in the prone position,
      has been utilized for the treatment of various disorders. However, there is
      limited literature addressing the postoperative complications of this procedure.
      In this study, the postoperative complications in patients treated with posterior
      ankle and hindfoot arthroscopy were analyzed to determine the type, rate, and
      severity of complications. METHODS: The study included 189 ankles in 186 patients
      (eighty-two male and 104 female; mean age, 37.1 +/- 16.4 years). The minimum
      duration of follow-up was six months, and the mean was 17 +/- 13 months. The most
      common preoperative intra-articular diagnoses were subtalar osteoarthritis (forty
      six ankles), an osteochondral lesion of the talus (forty-two), posterior ankle
      impingement (thirty-four), ankle osteoarthritis (twenty), and subtalar coalition
      (five). The most common extra-articular diagnoses were painful os trigonum (forty
      six), flexor hallucis longus tendinitis (thirty-two), and insertional Achilles
      tendinitis (five). RESULTS: The most common intra-articular procedures were
      osteochondral lesion debridement (forty-four ankles), subtalar debridement
      (thirty-eight), subtalar fusion (thirty-three), ankle debridement (thirty), and
      partial talectomy (nine). The most common extra-articular procedures were os
      trigonum excision (forty-eight), tenolysis of the flexor hallucis longus tendon
      (thirty-eight), and endoscopic partial calcanectomy (five). Complications were
      noted following sixteen procedures (8.5%); four patients had plantar numbness,
      three had sural nerve dysesthesia, four had Achilles tendon tightness, two had
      complex regional pain syndrome, two had an infection, and one had a cyst at the
      posteromedial portal. One case of plantar numbness and one case of sural nerve
      dysesthesia failed to resolve. CONCLUSIONS: Our experience demonstrated that
      posterior ankle and hindfoot arthroscopy can be performed with a low rate of
      major postoperative complications.

PMID- 22398739
TI  - Osteocutaneous pedicle flap transfer for salvage of transtibial amputation after
      severe lower-extremity injury.
AB  - BACKGROUND: A conventional transtibial amputation may not be possible when the
      zone of injury involves the proximal part of the tibia, or in cases of massive
      tibial bone and/or soft-tissue loss. The purpose of this study was to examine the
      outcomes of salvage of a transtibial amputation level with a rotational
      osteocutaneous pedicle flap from the ipsilateral hindfoot. METHODS: Fourteen
      patients who had an osteocutaneous pedicle flap from the ipsilateral foot were
      included in the study. Twelve patients were followed for more than twenty-four
      months (mean, 60.2 months) and were evaluated with use of the Sickness Impact
      Profile (SIP), Musculoskeletal Function Assessment (MFA), and a 100-ft (30.48-m)
      timed walking test. RESULTS: There were ten men and four women with mean age of
      43.2 years. Thirteen patients had a type-IIIB open tibial fracture, and one had
      extensive soft-tissue loss secondary to a burn. Four patients were treated for
      infection after the index procedure. There were no nonunions of the tibia to the
      calcaneus. Three patients underwent late reconstructive procedures to improve
      prosthetic fit. No patient required subsequent revision to a more proximal
      amputation level. Mean knee flexion was 139 degrees . CONCLUSIONS: A novel
      technique has been developed to salvage a transtibial amputation level with use
      of a rotational osteocutaneous flap from the hindfoot. In the absence of adequate
      tibial length and/or soft-tissue coverage to salvage the entire limb or to
      perform a conventional-length transtibial amputation, this technique is a highly
      functional alternative that does not require microvascular free tissue transfer.

PMID- 22398740
TI  - Comparison of forearm rotation allowed by different types of upper extremity
      immobilization.
AB  - BACKGROUND: The purpose of this study was to compare the active forearm pronation
      and supination allowed by a short arm splint, short arm cast, sugar tong splint,
      long arm splint, and long arm cast in normal, healthy subjects. METHODS: Forty
      healthy, right-handed volunteers (twenty men and twenty women) with a mean age of
      thirty-five years (range, twenty-three to sixty-six years) were recruited. Two
      examiners used a goniometer developed for the study to measure the active forearm
      supination and pronation in each subject with and without the application of the
      different types of upper extremity immobilization. Forearm pronation and
      supination were compared among the immobilization methods and between men and
      women. The inter-rater reliability of the measurements was evaluated with use of
      the intraclass correlation coefficient. RESULTS: The long arm cast decreased
      active forearm rotation to <10% of the value with no immobilization. The short
      arm cast, sugar tong splint, and long arm splint decreased active forearm
      rotation to <40% of the baseline measurement. No significant difference in active
      forearm supination or pronation was observed among the short arm cast, sugar tong
      splint, and long arm splint in the overall study cohort or in the men. However,
      forearm supination and pronation in the women differed significantly between the
      short arm cast and both the sugar tong splint and the long arm splint.
      CONCLUSIONS: The long arm cast provided the greatest restriction of forearm
      rotation. Overall, no significant difference in active forearm supination or
      pronation was observed among the short arm cast, sugar tong splint, and long arm
      splint.

PMID- 22398741
TI  - Giant cell tumor of the extremity: retrospective analysis of 621 Chinese patients
      from one institution.
AB  - BACKGROUND: There are no recent reports of giant cell tumors of bone in a large
      series of Chinese people. The present study was designed to review the
      epidemiological characteristics and outcomes of surgical management in a large
      series of Chinese patients with giant cell tumor of an extremity, treated at a
      single institution. METHODS: The records and images of 621 patients in whom a
      benign giant cell tumor in an extremity was treated between 1989 and 2009 were
      reviewed retrospectively. There were 359 male and 262 female patients. The mean
      age at diagnosis was 31.4 years (range, eleven to seventy-one years). Sixty-six
      percent of the giant cell tumors were localized around the knee. Surgical
      treatments primarily included curettage, extensive curettage, and resection. The
      median duration of follow-up was forty-nine months (range, eighteen to 256
      months). RESULTS: Giant cell tumor accounted for 13.7% of all primary bone tumors
      treated at our institution. Multivariate Cox regression analysis indicated that
      the only variable that contributed to recurrence-free survival was the type of
      surgical treatment. The local recurrence rate after extensive curettage was 8.6%,
      which was significantly lower than the 56.1% recurrence rate after curettage
      alone. Bone-grafting did not affect local tumor control after extensive
      curettage; the local recurrence rate was 11.1% if bone graft was used. Recurrent
      giant cell tumor can be treated by further curettage or resection, with
      acceptable re-recurrence rates of 6.7% and 9.3% respectively. The Musculoskeletal
      Tumor Society Score for patients treated with extensive curettage was 92.6%,
      which was significantly higher than that for patients treated with resection.
      Twenty-one (3.4%) of the 621 patients developed benign pulmonary metastasis, with
      a favorable outcome, and three patients presented with multifocal giant cell
      tumors. CONCLUSIONS: The incidence of giant cell tumor in the Chinese population
      may be higher than that in Western countries, and it has a male predilection. The
      results of the present study suggest that extensive curettage provides favorable
      local control and satisfactory functional outcomes.

PMID- 22398742
TI  - Lower extremity-specific measures of disability and outcomes in orthopaedic
      surgery.
AB  - Outcome measures may be simple questions or complex measures that assess multiple
      interrelated domains affecting treatment outcomes. Outcome measures should be
      relevant to patients, easy to use, reliable, valid, and responsive to clinical
      changes. Joint and disease-specific outcome measures have been developed for the
      hip, knee, and foot and ankle. Many of these measures would benefit from further
      research into their validity, reliability, and optimal applicability. General
      health measures and activity level scores should be included in outcome
      assessments after treatment for orthopaedic conditions.

PMID- 22398743
TI  - "Not statistically different" does not necessarily mean "the same": the important
      but underappreciated distinction between difference and equivalence studies.

PMID- 22398744
TI  - Women in orthopaedics--way behind the number curve.

PMID- 22398745
TI  - The best practice for rehabilitation after flexor tendon repair remains elusive:
      commentary on an article by Jan-Wiebe H. Korstanje, MSc, PhD, et al.:
      "Ultrasonographic assessment of flexor tendon mobilization: effect of different
      protocols on tendon excursion".

PMID- 22398746
TI  - In which position do we perform arthroscopy of the hindfoot--supine or prone?
      Commentary on an article by Florian Nickisch, MD, et al.: "Postoperative
      complications of posterior ankle and hindfoot arthroscopy".

PMID- 22398748
TI  - Solvent effects on electron-driven proton-transfer processes: adenine-thymine
      base pairs.
AB  - Time-Dependent Density Functional Theory (TD-DFT) computations, with M05-2X and
      PBE0 functionals, have been employed for a detailed study of the Electron-Driven
      Proton-Transfer (PT) processes in an Adenine-Thymine Watson-Crick Base Pair in
      the gas phase and in solution, with the bulk solvent described by the polarizable
      continuum model. In the gas phase, TD-DFT computations predict that the Adenine 
      > Thymine Charge Transfer (CT) excited state undergoes a barrierless PT reaction,
      in agreement with CC2 computations (S. Perun, A. Sobolewski, W. Domcke, J. Phys.
      Chem. A, 2006, 110, 9031.). The good agreement between the TD-DFT approach and
      CC2 results validates the former for the studies of excited state properties,
      excited state proton transfer reaction, and deactivation mechanisms in the DNA
      base pairs. Next, it is shown that inclusion of solvent effects significantly
      influences the possibility of both barrier-less excited state proton transfer and
      radiation-less deactivation through conical intersection with the ground state,
      affecting the energy of the CT excited state in the Franck-Condon region, the
      energy barrier associated to the PT process and the energy gap with the ground
      electronic state. These findings clearly indicate that environmental effects,
      with a special attention to proper treatment of dynamical solvation effects, have
      to be included for reliable computational analysis of photophysical and
      photochemical processes occurring in condensed phases.

PMID- 22398747
TI  - A critical role for the inducible proteasomal subunits LMP7 and MECL1 in cytokine
      production by activated murine splenocytes.
AB  - BACKGROUND AND PURPOSE: The proteasome is a multi-subunit complex that
      proteolytically cleaves proteins. The replacement of the constitutive proteasome
      subunits beta1, beta2, and/or beta5 with the IFNgamma-inducible subunits LMP2,
      MECL1, and/or LMP7 results in the 'immunoproteasome'. The inducible subunits
      change the cleavage specificities of the proteasome, but it is unclear whether
      they have functions in addition to this. The purpose of the present study was to
      determine the role of the proteasome in general, as well as LMP7 and MECL1
      specifically, with regard to cytokine production by activated primary
      splenocytes. METHODS: A LMP7/MECL1-null mouse was engineered to determine the
      roles of these subunits in cytokine production. Isolated splenocytes from wild
      type and LMP7/MECL1-/- mice were treated with lactacystin and activated with PMA
      and ionomycin and subsequently cytokine mRNA levels were quantified. RESULTS: The
      present study demonstrates that LMP7/MECL1 regulates the expression of IFNgamma,
      IL4, IL10, IL2Rbeta, GATA3, and t-bet. In contrast, the regulation of IL2, IL13,
      TNFalpha, and IL2Ralpha by the proteasome appears to occur independently of
      LMP7/MECL1. CONCLUSIONS: Collectively, the present study demonstrates that LMP7
      and MECL1 regulate cytokine expression, suggesting this system represents a novel
      mechanism for the regulation of cytokines and cytokine signaling.

PMID- 22398749
TI  - Illicit drug use in the flemish nightlife scene between 2003 and 2009.
AB  - AIMS: Given the importance of party people as innovators and early adaptors in
      the diffusion of substance use, and given the lack of longitudinal scope in
      studies of the nightlife scene, we explored changes in illicit drug use among
      young people participating in the nightlife scene in Flanders. METHODS: A survey
      among party people selected at dance events, rock festivals and clubs was held in
      the summer of 2003 and repeated in 2005, 2007 and 2009. In total, 2,812
      respondents filled in a questionnaire on the use of cannabis, ecstasy, cocaine,
      amphetamines, GHB and ketamine. RESULTS: The results of the multiple logistic
      regression analyses show that in the group of frequent pub visitors, the
      predicting probability of cannabis use increased over time, while the gap in drug
      use between dance music lovers and non-lovers of dance music narrowed. For
      cocaine use during the last year, an increase was found related to the housing
      situation (alone or with parents) of respondents. While the odds of using ecstasy
      decreased over the years, the odds of using GHB increased. CONCLUSION: We can
      conclude that monitoring emerging trends, which can be quickly observed in the
      nightlife scene, provides meaningful information for anticipating possible
      trends.

PMID- 22398750
TI  - Soluble tumor necrosis factor-related apoptosis-inducing ligand after
      percutaneous coronary intervention:  a potential biomarker for vascular
      remodeling.

PMID- 22398751
TI  - Cold urticaria patients exhibit normal skin levels of functional mast cells and
      histamine after tolerance induction.
AB  - Cold urticaria is a skin condition characterized by rapid appearance of itchy
      wheals and occasionally angioedema in response to cold stimulation.
      Antihistamines do not sufficiently protect all patients from symptoms, even when
      used in higher than standard doses. In these patients, desensitization to cold
      can be beneficial. The aim was to investigate whether desensitization can lower
      temperature thresholds and reduce release of histamine in the skin. Cold
      urticaria patients were subjected to desensitization and assessed for skin
      responses to cold stimulation and codeine before and after. Histamine levels
      mediated by cold and codeine were determined by cutaneous microdialysis before
      and after desensitization in patients and healthy controls. Desensitization to
      cold resulted in protection from cold-induced symptoms and lower temperature
      thresholds in six out of nine patients. Desensitization also prevented histamine
      release after skin exposure to cold. Surprisingly, skin histamine levels and
      release after codeine injection were found to be normal in desensitized patients.

PMID- 22398752
TI  - Sedentary behaviors and obesity in a low-income, ethnic-minority population.
AB  - BACKGROUND: Numerous studies have documented adverse health effects from
      prolonged sitting and TV viewing. These sedentary pastimes are linked to
      increased risk for obesity and other cardiometabolic risk factors. No studies,
      however, have examined these associations specifically in low-income, minority
      communities in the US. METHODS: This cross-sectional, community-based study was
      conducted in South Dallas, TX. Multivariable ordered logistic regression models
      were used to examine the association between sedentary behaviors (self-report)
      and measures of objectively assessed obesity (BMI, waist circumference). RESULTS:
      Among a low-income, ethnic-minority population, there were independent and
      significant associations between higher levels of sitting time, computer use, and
      transit time with elevated BMI (P < .05). Elevated waist circumference was also
      linked to increased sitting time, computer use, and transit time, yet without
      statistical significance. CONCLUSIONS: Increased time spent in passive-leisure
      activities is a risk marker for obesity in this population.

PMID- 22398753
TI  - A spread containing bioactive milk peptides Ile-Pro-Pro and Val-Pro-Pro, and
      plant sterols has antihypertensive and cholesterol-lowering effects.
AB  - Lifestyle intervention is recommended as the primary treatment for mild
      hypertension and hypercholesterolemia. We studied the effects of a spread
      containing bioactive milk peptides IPP and VPP, as well as plant sterols, on
      cardiovascular risk factors in 104 hypertensive, hypercholesterolemic subjects in
      a randomised, placebo-controlled double-blind intervention. Middle-aged subjects
      consumed 20 g day-1 of a spread containing 4.2 mg of IPP and VPP as well as 2 g
      of plant sterols for 10 weeks after a 2 week run-in period. Blood pressure was
      measured at home 3 times a week. Office blood pressure and 24 h ambulatory blood
      pressure measurements were performed at the end of the run-in and intervention
      periods. Blood samples were analysed for serum lipids, plasma glucose and
      inflammation markers. A significant decrease (-4.1 mmHg vs. -0.5 mmHg, p = 0.007)
      in systolic blood pressure was seen in the active group, compared to placebo at
      home measurements. Office blood pressure and 24 h nighttime or daytime ambulatory
      systolic or diastolic pressure did not differ between the groups. Total (-0.16
      vs. 0.25 mmol l-1, p = 0.005) and LDL cholesterol (-0.16 vs. 0.18 mmol l-1, p =
      0.006) decreased significantly in the active group compared to the placebo. No
      significant differences between groups were seen for plasma glucose or
      inflammation markers. The results thus suggest that milk peptides IPP and VPP and
      plant sterols, in a low-fat spread matrix, produce a clinically significant
      reduction in systolic blood pressure as well as serum total and LDL cholesterol
      without adverse effects. Functional foods that affect 2 major risk factors offer
      a safe and convenient way to reduce the risk of cardiovascular disease by
      supporting lifestyle intervention.

PMID- 22398754
TI  - Polypyrrole hollow fiber for solid phase extraction.
AB  - We have developed a solid-phase extraction method based on conductive polypyrrole
      (PPy) hollow fibers which were fabricated by electrospinning and in situ
      polymerization. The electrospun poly (e-caprolactone) (PCL) fibers were employed
      as templates for the in situ surface polymerization of PPy under mechanical
      stirring or ultrasonication to obtain burr-shaped or smooth fiber shells,
      respectively. Hollow PPy fibers, achieved by removing the PCL templates, were the
      ideal sorbents for solid phase extraction of polar compounds due to their
      inherent multi-functionalities. By using the hollow PPy fibers, two important
      neuroendocrine markers of behavioural disorders, 5-hydroxyindole-3-acetic acid
      and homovanillic acid, were successfully extracted. Under the optimized
      conditions, the absolute recoveries of the above two neuroendocrine markers were
      90.7% and 92.4%, respectively, in human plasma. Due to its simplicity,
      selectivity and sensitivity, the method may be applied to quantitatively analyse
      the concentrations of polar species in complex matrix samples.

PMID- 22398756
TI  - Determinants and outcomes associated with decisions to deny or to delay intensive
      care unit admission in Morocco.
AB  - PURPOSE: To report determinants and outcomes associated with decisions to deny or
      to delay intensive care unit (ICU) admission in critically ill patients. METHODS:
      An observational prospective study over a 6-month period. All adult patients
      triaged for admission to a medical ICU were included prospectively. Age, gender,
      reasons for requesting ICU admission, severity of underlying disease, severity of
      acute illness, mortality and ICU characteristics were recorded. Multinomial
      logistic regression analysis was used for evaluating predicting factors of
      refused ICU admission. RESULTS: ICU admission was requested for 398 patients: 110
      were immediately admitted (27.8%), 142 were never admitted (35.6%), and 146 were
      admitted at a later time (36.6%). The reasons for refusal were: too sick to
      benefit (31, 10.8%), too well to benefit (55, 19.1%), unit full (117, 40.6%), and
      more data about the patient were needed to make a decision (85, 29.5%).
      Multivariate analysis revealed that late ICU admission was associated with the
      lack of available ICU beds (OR 1.91; 95% CI 1.46-2.50; p = 0.003), cardiac
      disease (OR 7.77; 95% CI 2.41-25.04; p < 0.001), neurological disease (OR 3.78;
      95% CI 1.40-10.26; p = 0.009), shock and sepsis (OR 2.55; 95% CI 1.06-6.13; p =
      0.03), and metabolic disease (OR 2.84; 95% CI 1.11-7.30; p = 0.02). Factors for
      ICU refusal for never admitted patients were: severity of acute illness (OR 4.83;
      95% CI 1.11-21.01; p = 0.03), cardiac disease (OR 14.26; 95% CI 3.95-51.44; p <
      0.001), neurological disease (OR 4.05; 95% CI 1.33-12.28; p = 0.01) and lack of
      available ICU beds (OR 6.26; 95% CI 4.14-9.46; p < 0.001). Hospital mortality was
      33.3% (37/110) for immediately admitted patients, 43.8% (64/146) for patients
      admitted later and 49.3% (70/142) for never admitted patients. CONCLUSION:
      Refusal of ICU admission was correlated with the severity of acute illness, lack
      of ICU beds and reasons for admission request. Further efforts are needed to
      define which patients are most likely to benefit from ICU admission and to
      improve the accuracy of data on ICU refusal rates.

PMID- 22398755
TI  - Changes in the sublingual microcirculation and endothelial adhesion molecules
      during the course of severe meningococcal disease treated in the paediatric
      intensive care unit.
AB  - PURPOSE: The sublingual microcirculation can be visualised in real time using
      sidestream dark-field (SDF) imaging. Endothelial activation mediated through
      adhesion molecules may alter flow patterns in the microcirculation. We studied
      sublingual microcirculatory disturbances in children with meningococcal disease
      (MCD) and simultaneously measured plasma levels of adhesion molecules. METHOD:
      Twenty children admitted to the paediatric intensive care unit (PICU) with MCD
      were studied. Forty healthy children were controls. The sublingual
      microcirculation was assessed at admission and at timed intervals until
      extubation. The microvascular flow index (MFI), capillary density (CD),
      proportion of perfused vessels (PPV) and perfused vessel density (PVD) were
      measured using SDF imaging. Plasma intercellular adhesion molecule-1 (ICAM-1),
      vascular cell adhesion molecule-1 (VCAM-1), E-selectin and P-selectin were
      measured at admission and at timed intervals during the course of PICU treatment.
      RESULTS: Significant reductions in MFI, CD, PPV and PVD were found in children
      with MCD compared with controls (p < 0.005). These differences had resolved prior
      to extubation. Initial MFI values predicted the duration of mechanical
      ventilation, irrespective of the stage of illness at the time of presentation to
      PICU. There were negative correlations between the ICAM-1, VCAM-1 and E-selectin
      levels and the microcirculatory MFI and PPV values at the time of admission to
      PICU (p < 0.005). CONCLUSIONS: Microcirculatory dysfunction is present in
      children with severe MCD with improvement alongside clinical recovery.
      Microcirculatory dysfunction correlated with markers of endothelial activation.
      Sublingual SDF imaging is feasible in children ventilated on PICU for severe
      sepsis and may prove useful in studies assessing illness severity and therapy.

PMID- 22398757
TI  - What did they know, and  when did they know it?

PMID- 22398759
TI  - [Patient experiences--beneficial?].

PMID- 22398758
TI  - [Neuro Rehabilitation - highly specialized treatment].

PMID- 22398760
TI  - [About ritual circumcision and health care].

PMID- 22398761
TI  - [Ritual circumcision is health care].

PMID- 22398762
TI  - [Gestation].

PMID- 22398764
TI  - [Media attention].

PMID- 22398765
TI  - [Power switch is required].

PMID- 22398767
TI  - [Nevus or malignant melanoma?].

PMID- 22398768
TI  - Patient satisfaction  in rehabilitation of patients with multiple sclerosis.
AB  - BACKGROUND: The motor and non-motor symptoms of multiple sclerosis often result
      in a substantially reduced health-related quality of life. We surveyed patient
      satisfaction and own evaluation of the benefit of a period spent at a specialised
      rehabilitation centre. MATERIAL AND METHOD: All patients who spent a period at
      the Hakadal MS rehabilitation centre in 2010 were asked to complete a validated
      questionnaire designed to determine patient satisfaction with rehabilitation
      institutions. RESULTS: Of a total of 339 patients, 277 (82%) returned the
      questionnaire. The great majority of respondents were satisfied with the
      knowledge, cooperation, care and engagement of those providing treatment, as well
      as with the advance information provided and the premises. They also found that
      they were consulted concerning their rehabilitation programme and that they were
      prepared for the period following their stay. More than 85% of the respondents
      stated that the stay would have major or very great importance for their general
      qualify of life and physical health. A similar score for mental health was given
      by 83%, mastery of day-to-day tasks by 77% and participation in social activities
      by 71%. INTERPRETATION: Patients who have had stays at the Hakadal MS
      rehabilitation centre are satisfied and feel that the stay will be of great
      importance to their level of functioning and mastery.

PMID- 22398769
TI  - [Co-medication with benzodiazepines].
AB  - BACKGROUND: The various benzodiazepines have essentially the same mechanism of
      action and differ from one another primarily through differences in
      pharmacokinetics. There is no pharmacological basis for using more than one
      benzodiazepine for the same patient. The purpose of the study was to examine the
      occurence of co-medication with different types of benzodiazepines in Norway.
      MATERIAL AND METHOD: Data were obtained from the Norwegian Prescription Database.
      Patients who received at least one benzodiazepine in 2008 were included (n =
      299,185). The percentage of users who were co-medicated with at least two
      different benzodiazepines and the amounts prescribed were calculated and
      stratified by gender and age. RESULTS: It is highly probably that 27,861 (14,6%)
      of patients who received at least two benzodiazepines in the course of 2008 used
      two different benzodiazepines simultaneously. 13,267 (6.9%) of the patients were
      prescribed at least two different benzodiazepines on the same prescription. A
      larger number of women were co-medicated with different benzodiazepines, but the
      proportion of comedication was higher in men than in women, and most frequent in
      the age group 18-49 years. INTERPRETATION: There is an extensive and unfortunate
      prescription practice whereby the same patient is prescribed different
      benzodiazepines that are used concurrently. Patients who use different
      benzodiazepines concurrently are mainly prescribed these by one and the same
      doctor.

PMID- 22398770
TI  - [Pyonephrosis].

PMID- 22398771
TI  - [A woman in her 40s with rash and spots on the oral mucosa].

PMID- 22398772
TI  - A woman in her 50s  with manic psychosis.

PMID- 22398773
TI  - Demanding diagnostics--important diagnosis.

PMID- 22398774
TI  - Human  cells and the Norwegian Health Research Act.
AB  - The use of cells and cell lines is essential to the development of new knowledge
      and better medical therapies. Society is served by transparent and predictable
      regulations and practices on the use of human derived material. The National
      Committee for Medical and Health Research Ethics should publish guidelines
      setting out clearly how researchers should act with respect to such research.

PMID- 22398775
TI  - User surveys in psychiatry in the 1950s.

PMID- 22398776
TI  - Cancer  and palliative care in Mongolia.

PMID- 22398777
TI  - [Delirium or delir?].

PMID- 22398781
TI  - Lithographic compartmentalization of emulsion droplet templates for
      microparticles with multiple nanostructured compartments.
AB  - Complicated functional microparticles with complex nanostructured compartments
      have been synthesized from emulsion templates by lithographic compartment
      allocations. Our 'top-down-bottom-up' hybrid method will provide additional
      material engineering capability for the synthesis of advanced functional
      microparticles.

PMID- 22398780
TI  - Estrogen receptor beta potentiates the antiproliferative effect of raloxifene and
      affects the cell migration and invasion in HCT-116 colon cancer cells.
AB  - BACKGROUND: Estrogen receptor beta (ERbeta) is the predominant ER in the
      colorectal epithelium, whose expression is greatly reduced in colorectal cancer
      compared with normal colon tissue. Recent in vitro studies suggested that ERbeta
      may suppress tumor growth. No research was reported whether ERbeta can be used as
      therapeutic agent for colon cancer. METHODS: In this study, ERbeta gene
      constructed into adenoviral (Ad) vectors was used to treat colon cancer HCT-116
      cells alone or in combination with raloxifene. In vitro and in vivo studies were
      conducted to investigate the therapeutic effects of ERbeta and raloxifene in HCT
      116 cells. RESULTS: Our results indicated that, although Ad-ERbeta alone had no
      effect on the proliferation of HCT-116 cells, the combination of Ad-ERbeta with
      raloxifene significantly inhibited the proliferation of HCT-116 cells. The
      apparently apoptotic induction effects may partly explain the cytotoxicity of the
      two agents. The results of the study of ERbeta on migration and invasion of HCT
      116 cells demonstrated that overexpression of ERbeta significantly decreased cell
      migration and increased invasion of cells. The antitumor efficacies of ERbeta as
      well as raloxifene were further investigated on HCT-116 tumor bearing mice.
      Results demonstrated that both Ad-ERbeta and raloxifene individually inhibited
      tumor growth. The combination group showed the highest inhibitory efficiency
      compared with other three groups. CONCLUSION: These findings demonstrated that
      combined administration of Ad-ERbeta with raloxifene represents a promising colon
      cancer therapeutic strategy.

PMID- 22398782
TI  - Serum hemojuvelin and hepcidin levels in chronic kidney disease.
AB  - BACKGROUND: Hemojuvelin (HJV) has recently emerged as one of a number of
      significant regulators of iron homeostasis and hepcidin expression. Recently, an
      immunoassay has been developed to measure circulating levels of soluble HJV
      (sHJV). The aim of this study was to measure serum hepcidin and sHJV levels in a
      chronic kidney disease (CKD) population. METHODS: A total of 93 patients
      participated in the study (31 hemodialysis, 31 non-dialysis, 31 transplant
      recipients), and were matched for age and gender. Serum samples were taken for
      measurement of hepcidin-25 and sHJV, along with standard hematological,
      biochemical and inflammatory markers, and univariate/multivariate analyses were
      performed. RESULTS: Serum sHJV levels were markedly elevated in the hemodialysis
      patients (2,619 +/- 1,445 ng/ml) compared to the CKD (590 +/- 344 ng/ml) and
      transplant recipients (870 +/- 638 ng/ml) (p < 0.001), normal range 370-890
      ng/ml. There was a strong correlation between serum ferritin and sHJV, which
      remained after adjustment for potential confounders (beta 0.92, p < 0.001). In
      the univariate analysis, sHJV levels correlated with serum hepcidin but this was
      not evident in the multivariate analysis. No associations were seen between sHJV
      and markers of inflammation or eGFR. CONCLUSIONS: sHJV is elevated in
      hemodialysis patients compared to non-dialysis CKD patients. There was no
      association between sHJV and eGFR (in the non-dialysis groups), suggesting that
      factors other than decreased renal clearance are responsible for the high sHJV
      levels. The strong association between sHJV and ferritin suggests an
      interdependent relationship, although further studies are required to elucidate
      the possible mechanism(s) for this.

PMID- 22398784
TI  - A randomised assessment of the pharmacokinetic, pharmacodynamic and safety
      interaction between apixaban and enoxaparin in healthy subjects.
AB  - Following major orthopaedic surgery, guidelines usually recommend continued
      thromboprophylaxis after hospitalisation. The availability of an effective oral
      anticoagulant with an acceptable safety profile that does not require routine
      clinical monitoring may lead clinicians to switch patients from subcutaneous to
      an oral therapy either during hospitalisation or at discharge. The purpose of
      this study was to assess the effect of enoxaparin on the pharmacokinetics,
      pharmacodynamics and safety of apixaban, an oral, direct inhibitor of coagulation
      factor Xa. In this four-period, crossover study, 20 healthy subjects were
      randomised to receive single doses of apixaban 5 mg orally; enoxaparin 40 mg
      subcutaneously; apixaban 5 mg and enoxaparin 40 mg concomitantly; and apixaban 5
      mg followed 6 hours (h) after by enoxaparin 40 mg. Pharmacokinetics of apixaban
      were not affected by enoxaparin. Average peak pharmacodynamic effect, measured by
      anti-Xa activity, was 1.36 U/ml after administration of apixaban and was 0.42
      U/ml after enoxaparin. Following co-administration of apixaban and enoxaparin,
      peak anti-Xa activity was 42% higher than for apixaban alone. Following
      administration of enoxaparin 6 h after apixaban, peak anti-Xa activity was 15%
      higher than for apixaban alone. In conclusion, enoxaparin had no effect on the
      pharmacokinetics of apixaban. The increase in anti-Xa activity after co
      administration was modest and appeared to be additive. Peak anti-Xa activity
      increases are mitigated by separating administration of subcutaneous
      anticoagulation and apixaban when switching between therapies; the potential for
      pharmacodynamic interaction may be further mitigated by transitioning at the next
      scheduled dose (12 h).

PMID- 22398785
TI  - Cosmetic benefits of the central approach with video-assisted neck surgery in
      Graves' disease.

PMID- 22398786
TI  - Novel therapeutic targets for sepsis: regulation of exaggerated inflammatory
      responses.
AB  - Sepsis is a devastating and complex syndrome and continues to be a major cause of
      morbidity and mortality among critically ill patients at the surgical intensive
      care unit setting in the United States. The occurrence of sepsis and septic shock
      has increased significantly over the past two decades. Despite of highly
      dedicated basic research and numerous clinical trials, remarkable progress has
      not been made in the development of novel and effective therapeutics. The sepsis
      induced physiologic derangements are due largely to the host responses to the
      invading microorganism in contrast to the direct effects of the microorganism
      itself. Sepsis, the systemic inflammatory response to infection, is marked by
      dysregulated production of pro-inflammatory cytokines. Although pro-inflammatory
      cytokine production is normally indispensable to protect against pathogens and
      promote tissue repair, the dysregulated and prolonged production of these
      cytokines can trigger a systemic inflammatory cascade mediated by chemokines,
      vasoactive amines, the complement and coagulation system, and reactive oxygen
      species (ROS), amongst others. These mediators collectively lead to multiple
      organ failure, and ultimately to death. In this regard, the role of inflammation
      in the pathophysiology of sepsis, although still incompletely understood, is
      clearly critical. Recent findings resulting from vigorous investigations have
      contributed to delineate various novel directions of sepsis therapeutics. Among
      these, this review article is focused on new promising mechanisms and concepts
      that could have a key role in anti-inflammatory strategies against sepsis,
      including 1) "inflammasome": a multiprotein complex that activates caspase-1; 2)
      "the cholinergic anti-inflammatory pathway": the efferent arm of the vagus nerve
      mediated, brain-to-immune reflex; 3) "stem cells": unspecialized and
      undifferentiated precursor cells with the capacity for self-renewal and potential
      to change into cells of multiple lineages; 4) "milk fat globule-EGF factor VIII
      (MFG-E8)": a bridging molecule between apoptotic cells and phagocytes, which
      promotes phagocytosis of apoptotic cells.

PMID- 22398787
TI  - Treatment modalities for bleeding esophagogastric varices.
AB  - Bleeding from esophageal varices (EVs) or gastric varices (GVs) is a catastrophic
      complication of chronic liver disease. In this paper, we review the management of
      bleeding EVs and GVs. DIAGNOSIS OF EVS AND GVS: The grading system for
      esophagogastric varices proposed by the Japan Society for Portal Hypertension
      classifies GVs into those involving the cardia (Lg-c), the fundus (Lg-f), and
      both the cardia and the fundus (Lg-cf). In this review, we divide GVs into 2
      categories: Lg-c (cardiac varices: CVs) and Lg-cf or Lg-f (fundal varices: FVs).
      TREATMENT MODALITIES FOR EVS AND GVS: Treatment modalities for EVs and GVs
      include placement of a Sengstaken-Blakemore tube, pharmacologic therapy, surgery,
      interventional radiology, and endoscopic treatment. MANAGEMENT OF BLEEDING EVS
      AND GVS: In Japan, endoscopic treatment has recently become the therapy of choice
      for bleeding EVs or GVs. In other countries, especially the United States,
      vasoactive drugs and endoscopic treatment are routinely used to manage variceal
      hemorrhage. BLEEDING EVS: Endoscopic variceal ligation is useful for controlling
      bleeding from EVs. However, confirmation of ligation precisely at the site of
      bleeding is usually difficult in patients with massive variceal bleeding. The
      site of acute bleeding can generally be identified by means of water instillation
      and suction. Ligation is then performed at the bleeding point. If endoscopic
      hemostasis is unsuccessful, a Sengstaken-Blakemore tube is used as a temporary
      bridge to other treatments. Transportal obliteration is useful for blocking
      variceal blood flow. BLEEDING GVS: Endoscopic injection sclerotherapy with a
      tissue adhesive, such as N-butyl-cyanoacrylate or isobutyl-2-cyanoacrylate, is
      effective for acute bleeding from GVs. However, bleeding from the GV injection
      site and rebleeding from the rupture point have been reported in patients
      receiving endoscopic injection sclerotherapy. If endoscopic hemostasis is
      unsuccessful, a Sengstaken-Blakemore tube is used as a temporary bridge to other
      treatments. Balloon-occluded retrograde transvenous obliteration and transportal
      obliteration are useful for the treatment of uncontrolled bleeding from GVs.
      PREVENTION OF RECURRENT VARICEAL HEMORRHAGE: Given the high recurrence rate,
      survivors of an acute variceal hemorrhage should receive treatment to prevent
      recurrence. Complete eradication of EVs or GVs and maintenance of low portal
      venous pressure are essential for preventing recurrence of variceal hemorrhage.

PMID- 22398788
TI  - Applications of statistics to medical science, II overview of statistical
      procedures for general use.
AB  - Procedures of statistical analysis are reviewed to provide an overview of
      applications of statistics for general use. Topics that are dealt with are
      inference on a population, comparison of two populations with respect to means
      and probabilities, and multiple comparisons. This study is the second part of
      series in which we survey medical statistics. Arguments related to statistical
      associations and regressions will be made in subsequent papers.

PMID- 22398789
TI  - Cervical anterior fusion with the Williams-Isu method: clinical review.
AB  - Anterior decompression and fusion of the cervical spine is a widely accepted
      treatment for cervical canal disease. The Williams-Isu method involves cervical
      anterior fusion with autologous bone grafts from cervical vertebral bodies. Its
      advantages are a wide operative field, excellent graft fusion, the absence of
      problems related to the iliac donor site, and direct visualization of the nerve
      root. For detailed decompression of the cervical root, an ultrasonic bone curette
      (SONOPET, Stryker Japan K.K., Tokyo) may be useful. To prevent graft extrusion,
      bioabsorbable screws featuring a head are placed in 4 corners of the bone graft
      and are fixed with a tap on a part of the graft. The screws are visualized on
      postoperative X-ray, computed tomography, and magnetic resonance imaging studies.
      In 69 patients reported elsewhere there were no complications attributable to
      screw insertion, screw or graft extrusion, or surgery-related infections. When
      adequate bone cannot be harvested, a piece of ceramic hydroxyapatite is placed
      between the bone grafts. This sandwich method reinforces the graft, and
      radiological evidence suggests that it yields better results with respect to the
      angle and height of the fused segment. For the surgical treatment of cervical
      ossification of the posterior longitudinal ligament, a large vertebral bone
      window and a large bone graft are needed; this may result in postoperative
      radiological worsening. Radiological studies have shown that cervical
      ossification of the posterior longitudinal ligament can, as can cervical
      spondylosis, be addressed with the Williams-Isu method. Detailed radiological
      studies in patients treated with the Williams-Isu method have demonstrated that
      the range of motion and the disc height of the fused segment must be considered
      to prevent worsening in that segment after anterior fusion. The Williams-Isu
      method cannot completely correct cervical alignment, and great caution must be
      exercised in patients with preoperative malalignment. To reduce the levels to be
      fused in patients with multilevel lesions due to cervical disease, the Williams
      Isu method can be combined with the transvertebral approach. The transvertebral
      approach facilitated by the wide Williams-Isu window allows the root bifurcation
      area to be confirmed during the early stage of surgery and possible decompression
      along the root. Radiological examination has shown that the combination of the
      Williams-Isu method and transvertebral approach does not affect the fusion level
      compared with the Williams-Isu method alone and produces better results than does
      the transvertebral approach alone.

PMID- 22398790
TI  - Sequential analysis of myofibroblast differentiation and transforming growth
      factor-beta1/Smad pathway activation in murine pulmonary fibrosis.
AB  - Myofibroblasts play a critical role in tissue fibrosis. However, the
      intracellular signaling pathways in myofibroblast differentiation are poorly
      understood. Here, we studied the relationship between transforming growth factor
      beta (TGF-beta)/Smad pathway activation and myofibroblast differentiation in both
      in vivo and in vitro experiments. In murine bleomycin-induced pulmonary fibrosis,
      nuclear localization of phosphorylated Smad2/3 (p-Smad2/3) was observed in
      pulmonary fibrotic lesions 7 days after bleomycin injection, whereas alpha-smooth
      muscle actin (ASMA)-positive myofibroblasts appeared in the lesions at 14 days,
      when the cytoplasmic localization of p-Smad2/3 was observed. We also compared the
      effects of TGF-beta1 on myofibroblast differentiation and on type I collagen
      expression in a murine lung fibroblast cell line (MLg2908). TGF-beta1 induced
      rapid expression of p-Smad2/3 in nuclei, after which ASMA organization in the
      cytoplasm of fibroblasts was observed. However, TGF-beta1 produced no effect on
      the quantity of ASMA, either in mRNA levels or protein levels, even after the
      phosphorylation of Smad2/3. In contrast, TGF-beta1 upregulated the expression of
      type I collagen mRNA. These findings suggest that in pulmonary fibrosis the
      molecular mechanism of myofibroblast differentiation is complex and that the
      difference between ASMA expression and type I collagen expression is mediated by
      the TGF-beta/Smad pathway.

PMID- 22398791
TI  - Fetal heart rate classification proposed by the perinatology committee of the
      Japan Society of Obstetrics and Gynecology: reproducibility and clinical
      usefulness.
AB  - AIM: Intrapartum management guidelines based on fetal heart rate classification
      comprising a 5-tier system (Levels 1-5) was proposed by the Perinatology
      Committee of the Japan Society of Obstetrics and Gynecology (JSOG). This study
      aimed to assess the reproducibility and clinical usefulness of this
      classification. METHODS: For assessing intraobserver and interobserver
      reproducibility in the interpretation of fetal heart rate tracing, 2
      obstetricians reviewed 247 fetal heart rate tracings using the JSOG
      classification (Level 1, normal; Level 2, benign variant; Level 3, mild variant;
      Level 4, moderate variant; and Level 5, severe variant) and a subjective 3-tier
      classification (normal, equivocal, and ominous). In a separate series, we
      investigated whether the JSOG classification is related to early neonatal outcome
      and the delivery mode in 96 deliveries. RESULTS: Weighted kappa coefficients of
      intraobserver and interobserver reproducibility in the interpretation of fetal
      heart rate tracings based on the JSOG classification were 0.73 to 0.77 and 0.70,
      respectively. In the subjective classification, these values were 0.69 to 0.72
      and 0.59. There was a progressive increase in the rate of instrumental or
      cesarean deliveries across the 5 levels of the JSOG classification (P<0.001).
      Although, level 5 of the JSOG classification had a lower Apgar score and
      umbilical artery pH than did the other 4 levels (p<0.05), there were no
      significant differences among the other levels in regard to early neonatal
      outcome. CONCLUSIONS: This study demonstrated that both intraobserver
      reproducibility and interobserver reproducibility of the JSOG classification for
      interpreting FHR tracings were clinically acceptable. The results also suggest
      that the intervention according to the JSOG classification is useful for avoiding
      worsening early neonatal outcomes.

PMID- 22398792
TI  - The current status of blood pressure control among patients with hypertension: a
      survey of actual clinical practice.
AB  - We performed a cross-sectional survey to investigate actual clinical practices
      regarding blood-pressure control in patients with hypertension. From October 16
      to 31, 2008, postal questionnaires regarding the care of patients with
      hypertension were sent to members of the Kanagawa Physicians Association in
      Kanagawa, Japan. Data of 675 patients (mean age: 70.1 +/- 10.6 years, 301 men and
      374 women) were returned. The overall mean systolic blood pressure (BP) in these
      patients was 134.6 +/- 10.6 mm Hg, and diastolic BP was 76.2 +/- 8.3 mm Hg.
      According to the 2009 guidelines of the Japanese Society of Hypertension for the
      management of patients with hypertension, the target office BP was achieved by
      53.9% of all subjects; 29.7% of patients with diabetes mellitus, chronic kidney
      disease, or a history of myocardial infarction; 72.0% of elderly patients; 23.6%
      of nonelderly patients (younger than 65 years); and 75.4% of patients with
      cerebrovascular disease. Cross-sectional analysis showed that factors
      significantly associated with an increased likelihood of achieving the target
      office BP were: 1) usage of a larger number of antihypertensive agents in
      nonelderly patienys and in patients with diabetes mellitus, chronic kidney
      disease, or a history of myocardial infarction and: 2) usage of a smaller number
      of antihypertensive agents in elderly patients and patients with cerebrovascular
      disease. Further follow-up surveys are necessary to provide a full assessment.

PMID- 22398793
TI  - Two cases of flexor digitorum profundus avulsion due to enchondroma of the distal
      phalanx.
AB  - Avulsion of the flexor digitorum profundus tendon with fracture of the distal
      phalanx is rare. Moreover, enchondroma is less frequent in the distal phalanx. We
      report two unusual cases of avulsion of the flexor digitorum profundus tendon at
      its insertion in combination with pathological fracture of the distal phalanx due
      to enchondroma. Curettage and bone grafting were performed for an enchondroma of
      the distal phalanx. The flexor digitorum profundus tendon and the avulsed bone
      fragment were reinserted through the bone graft into the distal phalanx using the
      pull-out technique. With Strickland's criteria, the clinical results were
      evaluated as excellent in both cases. At the final follow-up examinations, there
      were no symptoms and no recurrence of the bone tumor. In the present cases, three
      dimensional computed tomography imaging was useful for diagnosing the flexor
      tendon avulsion, determining the preoperative identification the location of a
      ruptured tendon stump, and planning the operation to minimize the surgical wound.
      The recommended treatment for avulsion of the FDP tendon due to enchondroma is
      curettage, bone grafting of the resultant cavity, and reattachment of the tendon
      to ensure sufficient structural strength to permit secure fixation and early
      mobilization and, especially, to prevent flexion contracture of the finger
      because the stump of the flexor digitorum profundus is buried in the cavity of
      the distal phalanx.

PMID- 22398794
TI  - Recovery of normal hemodynamic activities after long-term medication in a patient
      with left internal carotid arterial occlusion.
AB  - BACKGROUND AND OBJECTIVE: Aspirin, clopidogrel, cilostazol, and statins are
      thought to reduce the risk of cerebral infarction in patients with intracranial
      arterial stenosis. We present a case of multiple intracranial arterial stenoses
      in which increased cerebral blood flow (CBF) was demonstrated after long-term
      medical therapy. CASE PRESENTATION: A 68-year-old man with a history of cerebral
      infarction showed complete occlusion of the left internal carotid artery with
      severe stenoses in the A1 segment of the left anterior cerebral artery (ACA) and
      the left posterior communicating artery resulting in poor visualization of the
      left middle cerebral artery (MCA) on magnetic resonance angiography (MRA).
      Administration of aspirin and clopidogrel prevented ischemia from recurring for 1
      year; however, the stenoses never improved. Technetium-99m-L, L-ethylcysteinate
      dimer single-photon emission computed tomography (SPECT) demonstrated a
      significant decrease in CBF in the territory of the left MCA. Anastomosis between
      the superficial temporal artery and the MCA was recommended to the patient
      because no supplementary blood supply was expected through either the left A1 or
      posterior communicating artery. However, the patient refused surgery because of
      the associated risks. To enhance vasodilation, clopidogrel was replaced by
      cilostazol. One year later, the stenoses had partially improved. Further
      treatment with aspirin, cilostazol, simvastatin, and nateglinide contributed to
      the significant increase in CBF with normal hemodynamics, as shown with
      acetazolamide-loading SPECT. CONCLUSION: The goal of treatment for intracranial
      arterial stenosis is to supply sufficient blood flow to the brain rather than to
      completely dilate the stenotic artery. Long-term treatment with aspirin,
      cilostazol, simvastatin, and nateglinide might help increase CBF in some patients
      with intracranial arterial stenosis.

PMID- 22398800
TI  - On the origin of oscillopsia during pedunculopontine stimulation.
AB  - We report a case of induced oscillopsia caused by deep brain stimulation (DBS) of
      the pedunculopontine nucleus (PPN). Recent reports have described involuntary
      oscillopsia during DBS of the PPN that patients have described as trembling
      vision. Here we substantiate this observation using infra-red eye tracking. It
      has been suggested that this phenomenon might be used as an indicator of accurate
      targeting of the PPN with DBS. Our observations suggest that this phenomenon may
      not be related to a constricted anatomical structure and therefore such practise
      may be unwise. Scrutiny has led us to believe that the oscillopsia in our patient
      is not caused by direct stimulation of the oculomotor nerve as suggested in a
      previous report, but by stimulation of fibres in the uncinate fasciculus of the
      cerebellum and the superior cerebellar peduncle, which in turn stimulate the
      saccadic pre-motor neurones in the brainstem.

PMID- 22398801
TI  - Urinary stone formers with hypocitraturia and 'normal' urinary pH are at high
      risk for recurrence.
AB  - BACKGROUND: Citrate is one of the most important inhibitors in urolithiasis.
      Hypocitraturia is a common risk factor in stone formers. Citrate excretion is
      regulated - amongst others - by acidosis and protein intake. A considerable
      number of stone formers, however, show hypocitraturia in the presence of normal
      urine pH levels. This is potentially due to defects in the renal tubular citrate
      carriers (NaDC 1 and 3) which may be genetically determined. PATIENTS AND
      METHODS: 350 consecutive stone formers were examined. Exclusion criteria were
      urinary tract infection, hypokalemia, and steatorrhea. The following parameters
      were measured: serum: creatinine, calcium, potassium, and uric acid; urine: pH
      profiles, citrate, calcium, uric acid, ammonia, urea, and creatinine. RESULTS:
      83/350 patients were hypocitraturic (48 males, 35 females). 14/83 had low urine
      pH (<= 6), 69/83 showed normal levels (>6). In the latter group there was a
      significantly higher recurrence rate (23 vs. 9%). The two groups were not
      different in serum parameters apart from uric acid. In urine, only pH and calcium
      (males) were significantly lower in the first group. Citrate did not correlate
      with urine pH and creatinine in the hypocitraturia-normal pH group, only with
      calcium in both sexes and urea and ammonia in females. In the hypocitraturia-low
      pH patients, there was no significant correlation between citrate and any other
      parameter tested. CONCLUSIONS: Hypocitraturia with normal urine pH is an entity
      indicating a high risk for recurrence. Since there was no correlation between
      citrate and pH, urea and ammonia, respectively, citrate excretion is not
      regulated in these patients as usual. There may be a link to calcium excretion.
      Potentially, these patients have defects in the renal tubular citrate carriers
      which may be genetically determined. Genetic examinations should be performed to
      elucidate a potential genetic disorder in hypocitraturia-normal pH stone formers.

PMID- 22398802
TI  - Clinical advances in hematology & oncology.

PMID- 22398803
TI  - Acquired hemophilia a: a current review of autoantibody disease.
AB  - Acquired hemophilia A (AHA) is a rare, potentially life-threatening hemorrhagic
      disorder that presents a complex clinical challenge. The immune-mediated
      production of autoantibodies, known as factor VIII inhibitors, often results in
      clinically significant soft tissue or post-procedural bleeding episodes in
      patients without a previous diagnosis of a bleeding disorder. Acquired antibodies
      against factor VIII are associated with an extensive list of conditions,
      including pregnancy, autoimmune disease, and malignancy. There is great potential
      for morbidity and mortality resulting from autoantibody development. Death is
      more frequent within the first few weeks after symptomatic manifestation, making
      prompt recognition and treatment vitally important. Treatment focuses on
      stabilization of initial bleeding and long-term eradication of the acquired
      inhibitor. As no randomized clinical trials have been conducted regarding
      treatment in this patient population, clinical expertise and experience continue
      to guide treatment recommendations. This report provides an algorithm for the
      diagnosis of AHA and outlines potential treatment recommendations, most notably
      concomitant use of recombinant factor VIIa (rF7a) and factor VIII inhibitor
      bypassing agent to control bleeding in patients not responsive to single-agent
      therapy, and use of rituximab and prednisone for inhibitor eradication therapy.

PMID- 22398804
TI  - Bone marrow transplant for multiple myeloma: impact of distance from the
      transplant center.
AB  - PURPOSE: This study investigated the impact of prognostic variables, including
      the distance a patient lives from a transplant center, on the outcome of
      autologous hematopoietic stem cell transplantation (ASCT) for multiple myeloma.
      METHODS: This retrospective analysis included 77 myeloma patients who received an
      ASCT at Dartmouth Hitchcock Medical Center between 1996 and 2009, 70 of whom were
      treated between 2002 and 2009. Using linear regression and univariate analysis,
      we examined the impact of distance from the transplant center on survival. Kaplan
      Meier curves identified overall and event-free survival. An association between
      distance from the transplant center and survival was examined using Cox
      regression analysis, while adjusting for patient-, disease-, and treatment
      related variables. RESULTS: Increasing distance from the transplant center
      correlated with improved overall survival (P=.004), but had no impact on disease
      free survival (P=.26). CONCLUSIONS: These results suggest that the distance from
      a transplant center should not be a barrier to ASCT for eligible patients with
      multiple myeloma.

PMID- 22398805
TI  - Molecular marker analyses from the SATURN trial.

PMID- 22398806
TI  - The incidence of venous thromboembolism in cancer patients: a real-world
      analysis.

PMID- 22398807
TI  - Breast cancer in focus: treatment options for triple-negative metastatic breast
      cancer.

PMID- 22398808
TI  - Harnessing the immune response.

PMID- 22398809
TI  - Burkitt lymphoma: analysis of the genome.

PMID- 22398810
TI  - Excessive therapeutic response in a case of blastic plasmacytoid dendritic cell
      neoplasm.

PMID- 22398811
TI  - Blastic plasmacytoid dendritic cell neoplasm.

PMID- 22398812
TI  - An unusual case of disseminated lymphadenopathy.

PMID- 22398813
TI  - Isolated myeloid sarcoma without bone marrow involvement.

PMID- 22398814
TI  - Farmer's lung in a case after bullectomy.
AB  - We present a case of farmer's lung (FL) with the primary presenting feature of a
      large bulla in the lung. A 70-year-old nonsmoking woman with dyspnea on exercise
      was referred for surgical resection of a large bulla in the lung. The
      postoperative evaluation of the lung tissue revealed a follicular lymphocytic
      alveolitis and loosely formed granulomas suspicious for hypersensitivity
      pneumonitis (HP). The patient had worked in farming since her youth. Dyspnea on
      exercise was the only symptom, but it was related to the large bulla. No other
      radiologic features of HP were shown in a high-resolution CT of the lung.
      Specific IgG antibodies against typical antigens of FL were detected,
      bronchoalveolar lavage demonstrated no lymphocytic alveolitis but an inhalative
      challenge with own hay was positive. A diagnosis of chronic FL was made. Despite
      lung emphysema being a possible reaction in FL, giant bullae as primary and
      single manifestation of this disease have not been reported before.

PMID- 22398815
TI  - [Magnetic resonance imaging and implantable cardiac devices. Current status and
      future perspectives of MR-compatible systems].
AB  - Conventional pacemakers and implantable cardioverter-defibrillators (ICD) have
      always been regarded as a contraindication to magnetic resonance imaging (MRI).
      MR-compatible systems represent a recent and particularly important innovation,
      since they will provide device patients with significantly improved access to MR
      examinations. However, the safe application of MR-compatible technology requires
      a detailed understanding of the strictly defined cardiologic and radiologic
      requirements and conditions that are to be adhered to before and during an MR
      examination. The present article gives an overview of problematic MR interactions
      with implanted devices, illustrates the most important aspects of MR-compatible
      pacemaker and ICD systems, analyzes their current clinical status, and offers a
      critical perspective.

PMID- 22398816
TI  - [Periinterventional antiplatelet therapy: from bench to bedside].
AB  - The recruitment and activation of blood platelets initiate ischemic events in
      patients with coronary artery diseases (myocardial infarction). Moreover,
      platelet activation and aggregation are key events triggering early and late
      thrombotic complications (stent thromboses) in patients successfully treated with
      coronary stent implantation. Hence, the inhibition of the thromboxane A2
      synthesis by aspirin and the ADP-receptor pathway by clopidogrel have drastically
      reduced the risk of ischemic complications following coronary stenting. However,
      clopidogrel has several inherent limitations, including the high incidence of non
      or low-responders and the increased risk of bleeding due to the prolonged
      persistence of its anti-platelet effect. The latter is of particular concern in
      patients who require non-deferrable surgery. In recent years, novel anti-platelet
      substances have been clinically evaluated and are now approved for use in
      patients. These substances offer several potential advantages over the previous
      strategies and could pave the way for more individualized anti-platelet regimens.
      In this review, we give an overview on the available clinical data evaluating the
      benefits of these novel anti-platelet substances.

PMID- 22398817
TI  - Considerations on the ICD-11 classification of psychotic depression.

PMID- 22398818
TI  - Switching of fluorescence mediated by a peroxynitrite-glutathione redox reaction
      in a porous silicon nanoreactor.
AB  - A nanostructured porous silicon chip functionalized with dichlorofluorescein is
      employed as a nanoreactor to respond to Reactive Oxygen Species (ROS) and to real
      time studying redox reactions.

PMID- 22398819
TI  - Co-occurrence of addictive behaviours: personality factors related to substance
      use, gambling and computer gaming.
AB  - AIM: To investigate co-occurrence and shared personality characteristics of
      problematic computer gaming, problematic gambling and substance use. METHODS:
      Cross-sectional survey data were collected from 2,553 German students aged 12-25
      years. Self-report measures of substance use (alcohol, tobacco and cannabis),
      problematic gambling (South Oaks Gambling Screen - Revised for Adolescents, SOGS
      RA), problematic computer gaming (Video Game Dependency Scale, KFN-CSAS-II), and
      of twelve different personality characteristics were obtained. RESULTS: Analyses
      revealed positive correlations between tobacco, alcohol and cannabis use and a
      smaller positive correlation between problematic gambling and problematic
      computer gaming. Problematic computer gaming co-occurred only with cannabis use,
      whereas problematic gambling was associated with all three types of substance
      use. Multivariate multilevel analyses showed differential patterns of personality
      characteristics. High impulsivity was the only personality characteristic
      associated with all five addictive behaviours. Depression and extraversion were
      specific to substance users. Four personality characteristics were specifically
      associated with problematic computer gaming: irritability/aggression, social
      anxiety, ADHD, and low self-esteem. CONCLUSIONS: Problematic gamblers seem to be
      more similar to substance users than problematic computer gamers. From a
      personality perspective, results correspond to the inclusion of gambling in the
      same DSM-V category as substance use and question a one-to-one proceeding for
      computer gaming.

PMID- 22398820
TI  - Effect of magnesium lactate dihydrate and calcium lactate monohydrate on 20-km
      cycling time trial performance.
AB  - Manufacturers of supplements containing magnesium lactate dihydrate and calcium
      lactate monohydrate claim improved athletic performance. Although energy can be
      produced through the lactate shuttle system, there is limited evidence to suggest
      that substantial quantities are available for human movement during exercise. The
      purpose of this study was to evaluate the effectiveness of lactate as a
      performance-enhancing substance. Nine recreational to competitive cyclists
      (VO2max = 52.46 +/- 11.8) completed 3 simulated 20-km time trials conducted on a
      Velotron. The first trial was used as a familiarization trial, and the last 2
      trials were counterbalanced ergogenic aid/placebo trials. To eliminate the
      possibility of bias, the study was conducted double blind. Dependent measures
      (time, mean power, heart rate [HR], and ratings of perceived exertion) for the 3
      trials were compared using repeated measures analysis of variance (p = 0.05).
      There were no significant differences between placebo and ergogenic aid in
      measures of time (38.78 +/- 5.87 minutes vs. 39.07 +/- 6.00 minutes; p = 0.212),
      mean power (236.40 +/- 74.8 W vs. 232.81 +/- 76.12 W; p = 0.342), and HR (167.36
      +/- 10.11 minutes vs. 163.70 +/- 13.07 minutes; p = 0.092). Ratings of perceived
      exertion for the placebo trial were significantly higher in relation to the
      ergogenic aid trial (15.97 +/- 0.72 vs. 15.70 +/- 0.85; p = 0.039). Although not
      significant, times during the placebo trials were faster in relation to the
      ergogenic aid trials. Ratings of perceived exertion were significantly higher in
      the placebo trials, which could reflect the trend toward faster times.
      Supplementation of magnesium lactate dihydrate and calcium lactate monohydrate
      does not appear to significantly improve times during a simulated 20-km time
      trial and therefore should not be recommended for use as an ergogenic aid.

PMID- 22398821
TI  - Can ephedrine pretreatment be effective in alleviating rocuronium injection pain?
AB  - OBJECTIVE: The aim of this randomized, double-blind, placebo-controlled study was
      to evaluate the effect of ephedrine pretreatment on the intensity of rocuronium
      injection pain when rocuronium was applied by timing principle and also to
      compare this effect with lidocaine and placebo. SUBJECTS AND METHODS: 120
      American Society of Anesthesiology risk score I-II patients scheduled for
      elective surgery under general anesthesia were randomized into three groups to
      receive either 70 MUg/kg ephedrine (ephedrine group, n = 40) or 0.5 mg/kg
      lidocaine (lidocaine group, n = 40) or 5 ml NaCl 0.9% (placebo group, n = 40) as
      pretreatment. Thirty seconds after pretreatment drugs, rocuronium 0.6 mg/kg was
      administered by the timing principle and rocuronium injection pain scores were
      recorded. Twenty seconds after rocuronium administration, anesthesia was induced
      with thiopental and the patient's trachea was intubated. Hemodynamic parameters
      and adverse effects were recorded. RESULTS: The overall frequency of having pain
      was 82.5, 52.5 and 22.5% in placebo, ephedrine and lidocaine groups,
      respectively. Although the frequency of mild and moderate pain scores was higher
      in the ephedrine group than in the lidocaine group, this difference was not
      statistically significant (p = 0.032 and p = 0.001, respectively). CONCLUSION:
      Although not as effective as lidocaine 0.5 mg/kg, 70 MUg/kg ephedrine
      pretreatment was able to alleviate rocuronium injection pain when rocuronium was
      applied by timing principle.

PMID- 22398822
TI  - Polycation-sensitive membrane electrode for determination of heparin based on
      controlled release of protamine.
AB  - A polycation-selective polymeric membrane electrode using dinonylnaphthalene
      sulfonate as an ion exchanger has been developed as a protamine controlled
      release system for potentiometric detection of heparin. The incorporation of
      tetradodecylammonium tetrakis(4-chlorophenyl)borate as a lipophilic salt in the
      membrane dramatically improves the sensor's selectivity towards protamine over
      sodium ions via influencing the activity coefficient of protamine in the
      membrane, and a stable potential baseline can be obtained in the presence of an
      electrolyte background. The electrostatic binding interaction between heparin and
      protamine decreases the concentration of free protamine released at the sample
      membrane interface and facilitates the stripping of protamine out of the membrane
      surface via the ion-exchange process with sodium ions, thus decreasing the
      membrane potential. Under optimal conditions, the proposed polymeric membrane
      electrode exhibits a linear relationship between the initial slope of the
      potential change and the heparin concentration in the range of 0.025-1.25 U mL(
      1) with an improved detection limit of 0.01 U mL(-1).

PMID- 22398823
TI  - The results of a 24-h pad test in Brazilian women.
AB  - INTRODUCTION AND HYPOTHESIS: The International Continence Society (ICS) adopted
      1.3 g as the normative value for the 24-h pad test. We hypothesized that this
      cutoff value may not be valid for women who live in countries with high
      temperatures. METHODS: We documented the 24-h pad test values of continent women
      in Brazil and investigated the factors that can influence in vaginal humidity.
      RESULTS: The sample consisted of 257 participants. The temperatures ranged from
      19 degrees C to 27.8 degrees C. The median increase in the weight of the pad was
      1.9 g (1.4-3.0 g, 95th percentile 4.4 g). Pad test results differed significantly
      between pre- and postmenopausal women (p = 0.026). There was a significant
      difference in the pad weights of women who use hormone therapy (p = 0.003).
      CONCLUSIONS: The value of the 24-h pad test established by the ICS was not valid
      for the investigated sample. Environmental conditions, menopausal status, and use
      of hormone therapy can interfere with the values of the pad test.

PMID- 22398824
TI  - Utility of preoperative endometrial assessment in asymptomatic women undergoing
      hysterectomy for pelvic floor dysfunction.
AB  - INTRODUCTION AND HYPOTHESIS: Uterine morcellation during laparoscopy for pelvic
      floor repair has prompted adoption of uterine screening tests by some surgeons.
      We report a case series of uterine malignancy incidentally diagnosed at the time
      of pelvic floor surgery. METHODS: We reviewed records from patients undergoing
      hysterectomy for pelvic organ prolapse (POP) and/or urinary incontinence (UI)
      from January 2004 to December 2009 and abstracted preoperative screening trends
      and final pathologic diagnoses. RESULTS: Of the 708 women in the study, 125 (18%)
      had preoperative endometrial biopsy (EB), 43 (6%) had pelvic ultrasound (US), and
      21 (3%) had EB and US. Surgical route included vaginal (58%), abdominal (23%),
      and laparoscopic (18%). Most (97.1%) final pathologic diagnoses were benign. Five
      cancers (0.6%) were detected; four of these women had normal preoperative
      screening, including EB (2), US (1), or both tests (1). CONCLUSIONS: Screening
      with EB + US was found to be ineffective in our cohort of patients due to the low
      prevalence of undetected uterine cancer in asymptomatic women planning POP/UI
      surgery.

PMID- 22398825
TI  - Symptoms, quality of life, and factors affecting women's treatment decisions
      regarding pelvic organ prolapse.
AB  - INTRODUCTION AND HYPOTHESIS: We performed an investigation of symptoms, quality
      of life (QOL), and factors affecting women's treatment choice of pelvic organ
      prolapse (POP). METHODS: Three hundred and eight women presenting with POP were
      assessed by Pelvic Floor Distress Inventory (PFDI), Pelvic Floor Impact
      Questionnaire (PFIQ), Short Form-36 (SF-36), Pelvic Organ Prolapse Quantification
      (POP-Q) system, and urodynamic studies. Treatment was arranged according to each
      woman's preference after counseling. Factors affecting treatment choice were
      evaluated. Descriptive statistics, chi-square or Fisher exact test, analysis of
      variance (ANOVA) test, and logistic regression analysis were used. RESULTS:
      Patients had high prevalence of urinary, prolapse, and bowel symptoms. Their QOL
      was impaired, with Urinary Impact Questionnaire (UIQ) higher than the Pelvic
      Organ Prolapse Impact Questionnaire (POPIQ) score and lower SF-36 score compared
      with the population norm. Logistic regression analysis indicated that
      complication from vaginal pessary, urodynamic stress incontinence (USI), stage of
      prolapse, and Pelvic Organ Prolapse Distress Inventory (POPDI) scoring were
      factors for choosing surgical treatment. CONCLUSIONS: Women with POP had great
      symptomatic distress and impaired QOL. Complication from vaginal pessary, USI,
      stage of prolapse, and POPDI scores were factors increasing the likelihood of the
      patient choosing surgical treatment.

PMID- 22398826
TI  - Vitamin D status in women with pelvic floor disorder symptoms.
AB  - INTRODUCTION AND HYPOTHESIS: Our aim was to characterize the relationship between
      25-hydroxyvitamin D [25(OH)D] status with pelvic floor symptom distress and
      impact on quality of life. METHODS: A retrospective chart review was performed in
      women with a 25(OH)D level drawn within 1 year of their gynecology/urogynecology
      visit. Validated questionnaires including the Colorectal-Anal Distress Inventory
      (CRADI)-8 and Incontinence Impact Questionnaire (IIQ-7) were used. Multivariate
      analyses characterized pelvic floor disorder (PFD) symptom differences among
      women by vitamin D status. RESULTS: We studied 394 women. Mean +/- standard
      deviation (SD) 25(OH)D levels were higher in women without than with PFD symptoms
      (35.0 +/- 14.1 and 29.3 +/- 11.5 ng/ml, respectively (p < 0.001)]. The prevalence
      of vitamin D insufficiency was 51% (136/268). CRADI-8 and IIQ-7 scores were
      higher among women with vitamin D insufficiency (p = 0.03 and p = 0.001,
      respectively). Higher IIQ-7 scores were independently associated with vitamin D
      insufficiency (p < 0.001). CONCLUSIONS: Insufficient vitamin D is associated with
      increased colorectal symptom distress and greater impact of urinary incontinence
      on quality of life.

PMID- 22398827
TI  - Incidence and risk factors of postoperative urinary tract infection after
      uterosacral ligament suspension.
AB  - INTRODUCTION AND HYPOTHESIS: We assessed the incidence of and risk factors for
      developing urinary tract infection (UTI) after uterosacral ligament suspension
      (USLS). METHODS: Retrospective analysis of patients undergoing USLS in 2008-2009
      was performed. Postoperative UTI was defined as a positive urine culture within 1
      month following surgery. Factors analyzed were patient age, body mass index,
      parity, history of UTI before surgery, passing voiding trial, discharge with
      Foley catheter or intermittent self-catheterization, antibiotics at discharge,
      history of diabetes or renal disease, and surgeon. RESULTS: Surgical records from
      169 patients were reviewed. Twenty-three patients (14%) developed UTI. There were
      no differences in preoperative factors between patients who developed UTI and
      those who did not. Subgroup analysis revealed those patients who went home with a
      Foley catheter and did not receive antibiotics had the highest proportion of UTI.
      CONCLUSION: Patients requiring Foley catheter at discharge following vaginal
      prolapse repair are at highest risk for UTI and require prophylactic antibiotics.

PMID- 22398828
TI  - Diagnosis of interstitial cystitis/bladder pain syndrome in women with chronic
      pelvic pain: a prospective observational study.
AB  - INTRODUCTION AND HYPOTHESIS: This study assesses the prevalence of interstitial
      cystitis (IC)/bladder pain syndrome (BPS) in women with chronic pelvic pain
      (CPP). METHODS: This was a prospective study of 150 women undergoing laparoscopy
      as investigation for CPP in an Endometriosis and Pelvic Pain unit. Preoperative
      questionnaires [demographic details, pelvic pain symptoms, the Pelvic Pain and
      Urgency/Frequency (PUF) and O'Leary-Sant (OLS) Symptom and Problem Index scores]
      were completed, and concurrent standardized cystoscopy with hydrodistention
      performed at laparoscopy. The primary outcome measures the proportion of IC in
      this group, defined by presence of glomerulations with CPP and urinary symptoms
      (urinary frequency, nocturia, urgency). The secondary outcome measures the
      proportion of BPS [defined by the European Society of the Study of Interstitial
      Cystitis (ESSIC)]. RESULTS: IC was diagnosed in 48/150 (32%) individuals, and
      80/150 (53%) had BPS. There were no significant differences in symptomatology or
      questionnaire results between groups with and without IC. Women with BPS had
      higher PUF (17.2 vs 12.9, p < 0.001), OLS Symptom (8.2 vs 6.0, p = 0.001) and
      Problem (7.5 vs 4.2, p < 0.001) scores and more severe pain symptoms. Visually
      proven endometriosis was seen in 90/150 (60%), and 27/150 (18%) had both
      endometriosis and IC. Of the 80 women with BPS, 45/80 (60%) had endometriosis.
      CONCLUSIONS: The prevalence of IC/BPS varies depending on the definition used.
      This study showed IC in 32% of women with CPP based on symptoms and presence of
      glomerulations. BPS as defined by ESSIC was diagnosed in 53%. History and
      questionnaires did not correlate with positive cystoscopic findings.

PMID- 22398829
TI  - MR imaging of acute cervical spinal ligamentous and soft tissue trauma.
AB  - The increasing availability of magnetic resonance imaging (MRI) and the high
      sensitivity of MRI for soft tissue injury are resulting in the increased use of
      MRI for the evaluation of acute trauma. As cervical spine injury can have a
      devastating consequence, MRI is being more commonly used to evaluate cervical
      spine injury in the acute setting, necessitating emergent interpretation by the
      on-call radiologist. Unless one is formally trained in a trauma center, the MRI
      findings of soft tissue and ligamentous cervical spine injury may not be fully
      appreciated. The goal of this pictorial review is to familiarize the reader with
      some of the more common soft tissue, vascular, and ligamentous injuries seen on
      MRI of the cervical spine in the emergent setting.

PMID- 22398830
TI  - Pseudocyst forms of Trichomonas vaginalis from cervical neoplasia.
AB  - Trichomonas vaginalis, a flagellated protozoan parasite causes a variety of
      adverse health consequences in both men and women. The parasite exists in the
      trophozoite and the pseudocystic stage. The study reports for the first time that
      pseudocyst forms of T. vaginalis isolated from cervical neoplasia (CN) patients
      demonstrated distinct, different and significant in vitro growth profiles when
      grown in vitro cultures from day 1 up to day 5 (p<0.05, Mann-Whitney test) when
      compared with the same life cycle stages isolated from non-cervical neoplasia but
      symptomatic patients (NCN). Pseudocysts from CN and NCN isolates remained viable
      in distilled water until 3 h 10 min and 2 h 10 min, respectively. The nucleus of
      pseudocysts in CN isolates using acridine orange and DAPI showed more intense
      staining revealing higher nuclear content. The FITC-labeled Concanavalin A
      stained stronger green fluorescence with surface of pseudocysts in CN isolates
      showing more rough and creased surface with higher numbers of deep micropores
      with larger numbers of chromatin masses, vacuoles, and hydrogenosomes. The study
      confirms that pseudocystic stage from CN, despite the uniformity in appearance of
      being rounded and showing no motility without a true cyst wall under light
      microscopy, demonstrated different biochemical, surface, and ultrastructural
      properties. The study provides evidence that phenotypic variant forms of
      pseudocysts does exist and possibly does play a role in exacerbating cervical
      cancer.

PMID- 22398831
TI  - Therapeutic effect of alpha lipoic acid combined with praziquantel on liver
      fibrosis induced by Schistosoma mansoni challenged mice.
AB  - Schistosomiasis is an endemic disease in 74 countries causing more than 250,000
      deaths every year. Accordingly, the development of an effective drug for
      eradication of schistosomiasis is an open research field. The current
      chemotherapy for control is praziquantel (PZQ). However, PZQ does not improve
      liver fibrosis. Therefore, the aim of this study is to evaluate the combined
      effect of alpha lipoic acid (ALA) with PZQ on the liver fibrosis induced by
      Schistosoma mansoni challenged mice. Evaluation was based on the worm burden
      count, ova load, granuloma size, and histopathology of the liver. Reduced
      glutathione (GSH) was measured in the tissue as a biomarker for impaired
      antioxidant function. Malondialdehyde (MDA) was also measured in the tissue as a
      biomarker for oxidative stress. The serum level of matrix metalloproteinase 1 was
      measured as a biomarker for fibrotic status of the liver. Liver function enzymes
      such as ALT, AST, and GGT were also measured. Four groups of ten mice each were
      used in this study. The first group was infected with 50 +/- 10 S. mansoni
      cercariae. The second group was also infected and was treated with PZQ 9 weeks
      post-infection (PI). The third group was treated with PZQ and ALA 9 weeks PI. The
      fourth group was used a healthy control. The present study revealed remarkable
      improvement in all parameters measured (parasitological and biochemical) as well
      as significant improvement of hepatic pathology in the third group which was
      treated with PZQ and ALA. The treatment of mice with PZQ and ALA results in
      reduction in the worm burden, egg count, and granuloma size. Furthermore, this
      combined treatment increased the tissue level of the antioxidant (GSH) and
      decreased the tissue level of MDA in this group.

PMID- 22398833
TI  - Update on the prevalence of the hookworm, Uncinaria lucasi, in northern fur seals
      (Callorhinus ursinus) on St. Paul Island, Alaska, 2011.
AB  - Prevalence of hookworms (Uncinaria lucasi Stiles, 1901) was determined in the
      northern fur seal (Callorhinus ursinus Linnaeus, 1758) on St. Paul Island (SPI),
      Alaska in July and August, 2011. Three of 61 (4.9%) dead pups harbored 1 to 13
      adult hookworms each in their intestines. Parasitic larvae (L(3)) of hookworms
      were recovered from the blubber of 4 of 133 (3%) of subadult males (SAMs)
      examined. One parasitic L(3) was detected from each infected SAM. Adult U. lucasi
      (n = 3) were found in the intestine of 1 of 105 SAMs examined (0.95%). This is
      the first documented finding of adult U. lucasi in SAMs of the northern fur
      seals. Continued low prevalence of hookworms the last several years parallels the
      tremendous decline in the number of fur seals on SPI over a similar time period.

PMID- 22398832
TI  - Mosquitocidal activity of Solanum xanthocarpum fruit extract and copepod
      Mesocyclops thermocyclopoides for the control of dengue vector Aedes aegypti.
AB  - The present study was carried out on Solanum xanthocarpum fruit extract and
      copepods Mesocyclops thermocyclopoides, which were assessed for the control of
      dengue vector, Aedes aegypti, under laboratory conditions. The medicinal plants
      were collected from the outskirts of Bharathiar University, Coimbatore, Tamil
      Nadu, India. The shade-dried fruit materials were extracted by employing the
      Soxhlet apparatus with methanol (organic solvent) 8 h and the extracts were
      filtered through a Buchner funnel with Whatman number 1 filter paper. The fruit
      extracts were concentrated at reduced temperature on a rotary vacuum evaporator
      and stored at a temperature of 4 degrees C. S. xanthocarpum fruit extract (SXFE)
      at 100, 150, 200, 250, and 300 ppm caused significant mortality of Ae. aegypti.
      The LC(50) and LC(90) of S. xanthocarpum against the first to fourth instar
      larvae and pupae were 170.91, 195.07, 221.45, 253.18, and 279.52 ppm and 320.62,
      366.48, 410.20, 435.16, and 462.10 ppm, respectively. A study was conducted to
      test whether the predatory efficiency of copepods on first instars changed in the
      presence of SXFE. The percentage of predatory efficiency of copepod was 6.5 % in
      treatments without SFXE and the percentage of predatory efficiency increased up
      to 8.7 % when copepods were combined with SFXE. This increase in predation
      efficiency may be caused by detrimental effects of the SFXE active principle
      compound (solanocarpine and solanocarpidine) on the mosquito larvae. Repeated
      application of fruit extract of S. xanthocarpum does not cause changes in copepod
      populations because fruit extract is highly degradable in the environment.
      Therefore, the present investigation clearly exhibits that the fruit extract of
      S. xanthocarpum and copepod M. thermocyclopoides could serve as a potential of
      highest mortality rate against the mosquito larvae under laboratory conditions.
      This is a new eco-friendly approach for the control of Ae. aegypti mosquito as
      target species. Therefore, this study provides the first report on the combined
      effect of mosquitocidal activity of this fruit extract and copepods of M.
      thermocyclopoides against dengue vector Ae. aegypti from India.

PMID- 22398834
TI  - Occurrence of bovine giardiasis and endemic genetic characterization of Giardia
      duodenalis isolates in Heilongjiang Province, in the Northeast of China.
AB  - To determine the prevalence of bovine giardiasis in Heilongjiang Province in
      China and to molecularly characterize Giardia duodenalis, feces were collected
      from 814 dairy and beef cattle ranging in age from 6 days to 9 years. Clinical
      symptoms of diarrhea were recorded at the time of sampling. The G. duodenalis
      infection rate in cattle was 5.2 % (42/814) as determined by Lugol's iodine
      staining. G. duodenalis assemblages and subtypes were genetically diagnosed by
      sequence analysis of the triosephosphate isomerase (TPI) gene. Three assemblages
      were identified, representing A (n = 1), B (n = 18), and E (n = 24), with a mixed
      infection case of assemblages A and E. High heterogeneity was also observed
      within assemblages B and E at the TPI locus. Among the assemblages, eight
      subtypes of assemblage B and three subtypes of assemblage E were found to be
      novel subtypes. Findings on assemblages A and B are of public health importance.
      The zoonotic potential of bovine giardiasis needs to be further assessed by
      extensive genetic data of assemblages A and B from humans at the subtype level.
      The newly found subtypes of assemblages B and E imply that the evaluation of
      geographically distributed subtypes is of importance.

PMID- 22398837
TI  - Helicity inversion from left- to right-handed square planar Pd(II) complexes:
      synthesis of a diastereomer pair from a single chiral ligand and their structure
      dynamism.
AB  - A diastereomer pair of left- and right-handed square planar Pd(II) complexes was
      synthesized from a single chiral ligand as kinetic and thermodynamic products.
      Helicity inversion between the diastereomers occurred rapidly under thermal and
      microwave irradiation conditions.

PMID- 22398835
TI  - Immunolocalization of arginine kinase (AK) in Toxocara canis, Toxocara vitulorum,
      and Ascaris lumbricoides.
AB  - Arginine kinase (AK) is a member of the phosphagen kinase family. AK plays a
      major role in cellular energy metabolism in invertebrates including nematodes. In
      the present study, we performed the direct immunofluorescence test to determine
      the immunolocalization of AK in different stages of the life cycle (eggs, larvae,
      and adult worms) of Toxocara canis, Toxocara vitulorum, and Ascaris lumbricoides.
      Our results indicated variable levels of expression of AK in different stages.
      Moreover, strong fluorescence was observed in cleaving eggs than in dormant eggs.
      The highest activity of the enzyme was observed in the fully developed eggs. This
      may be due to high expression of AK in embryonic development, which is associated
      with increased energy demand due to cleavage and cellular differentiation.
      Surprisingly, expression of AK is significantly higher in the middle part and
      posterior end compared to anterior end of the larvae. In addition, AK is highly
      concentrated in cellular and metabolically active parts of the body such as
      hypodermis, muscle, intestine, ovaries, oviducts, and uterus, while it is absent
      in noncellular areas like cuticle. The present study revealed the presence of AK
      in T. canis, A. lumbricoides, and T. vitulorum and that it plays a major role in
      energy metabolism of these nematodes. Interestingly, antiserum was prepared
      against the recombinant T. canis AK and reacts with the native AKs of T. canis,
      A. lumbricoides, and T. vitulorum. AK levels could vary in relation to maximum
      potential rates of ATP turnover, oxidative capacity, and energy output. Further
      studies on subcellular localization of AK in these important helminths provide
      new information for researchers to develop effective anthelmintics against the
      parasites of veterinary and of public health importance.

PMID- 22398836
TI  - Surface-enhanced Raman scattering (SERS) optrodes for multiplexed on-chip sensing
      of nile blue A and oxazine 720.
AB  - The fabrication and on-chip integration of surface-enhanced Raman scattering
      (SERS) optrodes are presented. In the optrode configuration, both the laser
      excitation and the back-scattered Raman signal are transmitted through the same
      optical fiber. The SERS-active component of the optrode was fabricated through
      the self-assembly of silver nanoparticles on the tip of optical fibers. The
      application of SERS optrodes to detect dyes in aqueous solution indicated a limit
      of quantification below 1 nM, using nile blue A as a molecular probe. Using the
      optrode-integrated microfluidic chip, it was possible to detect several different
      dyes from solutions sequentially injected into the same channel. This approach
      for sequential detection of different analytes is applicable to monitoring on
      chip chemical processes. The narrow bandwidth of the vibrational information
      generated by SERS allowed solutions of different compositions of two chemically
      similar dyes to be distinguished using a dilution microfluidic chip. These
      results demonstrate the advantages of the SERS-optrode for microfluidics
      applications by illustrating the potential of this vibrational method to quantify
      components in a mixture.

PMID- 22398838
TI  - A commentary on the lead positioning for deep brain stimulation in the
      pedunculopontine tegmental nucleus in a patient affected by multiple system
      atrophy.

PMID- 22398839
TI  - DNAzyme logic-controlled biofuel cells for self-powered biosensors.
AB  - The integration of a biosensor employing a DNAzyme logic system within a biofuel
      cell is presented. The self-powered DNAzyme logic biosensor conforms with INH
      logic operation and generates power output in accordance with a truth table. The
      new concept of logic-activated DNAzyme by the input signals has wide-ranging
      implications in the self-powered diagnostics domain.

PMID- 22398840
TI  - Deletion of Siah-interacting protein gene in Drosophila causes cardiomyopathy.
AB  - Drosophila is a useful model organism in which the genetics of human diseases,
      including recent advances in identification of the genetics of heart development
      and disease in the fly, can be studied. To identify novel genes that cause
      cardiomyopathy, we performed a deficiency screen in adult Drosophila. Using
      optical coherence tomography to phenotype cardiac function in awake adult
      Drosophila, we identified Df(1)Exel6240 as having cardiomyopathy. Using a number
      of strategies including customized smaller deletions, screening of mutant
      alleles, and transgenic rescue, we identified CG3226 as the causative gene for
      this deficiency. CG3226 is an uncharacterized gene in Drosophila possessing
      homology to the mammalian Siah-interacting protein (SIP) gene. Mammalian SIP
      functions as an adaptor protein involved in one of the beta-catenin degradation
      complexes. To investigate the effects of altering beta-catenin/Armadillo
      signaling in the adult fly, we measured heart function in flies expressing either
      constitutively active Armadillo or transgenic constructs that block Armadillo
      signaling, specifically in the heart. While, increasing Armadillo signaling in
      the heart did not have an effect on adult heart function, decreasing Armadillo
      signaling in the fly heart caused the significant reduction in heart chamber
      size. In summary, we show that deletion of CG3226, which has homology to
      mammalian SIP, causes cardiomyopathy in adult Drosophila. Alterations in
      Armadillo signaling during development lead to important changes in the size and
      function of the adult heart.

PMID- 22398841
TI  - Opportunities in IT Support of Workflow & Information Flow in the Emergency
      Department Digital Imaging Process.
AB  - The goal of this study is to examine workflow and information flow in the
      emergency department (ED) digital imaging process to identify features of an
      optimized system. Radiological imaging (x-rays, CT scans, etc) is unique in the
      ED setting, as the need for fast turn-around time and interactive communication
      between radiologists and emergency physicians is different than that of most
      other healthcare settings. The information technology systems which are used by
      both radiologists and emergency physicians to support these processes have been
      designed with a focus on the routine workflow of radiologists. We report the
      results of 14 hours of naturalistic observations of the use of digital imaging
      systems by a total of 22 ED and radiology staff. A hierarchical task analysis and
      an information process diagram are presented, and disparate theories that groups
      in the system have about other groups were discovered, particularly in the
      communication of clinical information.

PMID- 22398842
TI  - Outbreak of Shiga toxin-producing Escherichia coli O111 infections associated
      with a correctional facility dairy - Colorado, 2010.
AB  - On April 20, 2010, the Colorado Department of Public Health and Environment
      (CDPHE) was notified by correctional authorities regarding three inmates with
      bloody diarrhea at a minimum-security correctional facility. The facility, which
      houses approximately 500 inmates, is a designated work center where inmates are
      employed or receive vocational training. Approximately 70 inmates work at an
      onsite dairy, which provides milk to all state-run correctional facilities in
      Colorado. CDPHE immediately began an investigation and was later assisted by the
      High Plains Intermountain Center for Agricultural Health and Safety at Colorado
      State University and by CDC. This report describes the results of the
      investigation, which determined that the illnesses were caused by Shiga toxin
      producing Escherichia coli O111 (STEC O111) infections. During April-July, 10
      inmates at the facility received a diagnosis of laboratory-confirmed STEC O111
      infection, and a retrospective prevalence study of 100 inmates found that, during
      March-April, 14 other inmates had experienced diarrheal illness suspected of
      being STEC O111 infection. Pulsed-field gel electrophoresis (PFGE) testing
      indicated that STEC O111 isolates from inmates matched STEC O111 isolates from
      cattle at the onsite dairy. An environmental investigation determined that
      inmates employed at the dairy might have acquired STEC O111 infection on the job
      or transported contaminated clothing or other items into the main correctional
      facility and kitchen, thereby exposing other inmates. To prevent similar
      outbreaks in correctional facilities, authorities should consult with public
      health officials to design and implement effective infection control measures.

PMID- 22398843
TI  - Outbreak of cryptosporidiosis associated with a firefighting response - Indiana
      and Michigan, June 2011.
AB  - On June 20, 2011, the Indiana Department of Homeland Security notified the
      Indiana State Department of Health (ISDH) of an Indiana fire station that
      reported gastrointestinal illness among a substantial percentage of their
      workers, causing missed workdays and one hospitalization as a result of
      cryptosporidiosis. All ill firefighters had responded to a barn fire in Michigan,
      15 miles from the Michigan-Indiana border on June 6; responding firefighters from
      Michigan also had become ill. ISDH immediately contacted the Michigan Department
      of Community Health (MDCH) concerning this outbreak. The investigation was led by
      MDCH in partnership with ISDH and the Michigan local health department (LHD).
      Among 34 firefighters who responded to the fire, 33 were interviewed, and 20
      (61%) reported gastrointestinal illness <=12 days after the fire. Cryptosporidium
      parvum was identified in human stool specimens, calf fecal samples, and a
      swimming pond. Based on these findings, the following public health
      recommendations were issued: 1) discontinue swimming in the pond, 2) practice
      thorough hygiene to reduce fecal contamination and fecal-oral exposures, and 3)
      decontaminate firefighting equipment properly. No additional primary or secondary
      cases associated with this exposure have been reported. The findings highlight a
      novel work-related disease exposure for firefighters and the need for public
      education regarding cryptosporidiosis prevention.

PMID- 22398844
TI  - Vital signs: preventing Clostridium difficile infections.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is a common and sometimes fatal
      health-care-associated infection; the incidence, deaths, and excess health-care
      costs resulting from CDIs in hospitalized patients are all at historic highs.
      Meanwhile, the contribution of nonhospital health-care exposures to the overall
      burden of CDI, and the ability of programs to prevent CDIs by implementing CDC
      recommendations across a range of hospitals, have not been demonstrated
      previously. METHODS: Population-based data from the Emerging Infections Program
      were analyzed by location and antecedent health-care exposures. Present-on
      admission and hospital-onset, laboratory-identified CDIs reported to the National
      Healthcare Safety Network (NHSN) were analyzed. Rates of hospital-onset CDIs were
      compared between two 8-month periods near the beginning and end of three CDI
      prevention programs that focused primarily on measures to prevent intrahospital
      transmission of C. difficile in three states (Illinois, Massachusetts, and New
      York). RESULTS: Among CDIs identified in Emerging Infections Program data in
      2010, 94% were associated with receiving health care; of these, 75% had onset
      among persons not currently hospitalized, including recently discharged patients,
      outpatients, and nursing home residents. Among CDIs reported to NHSN in 2010, 52%
      were already present on hospital admission, although they were largely health
      care related. The pooled CDI rate declined 20% among 71 hospitals participating
      in the CDI prevention programs. CONCLUSIONS: Nearly all CDIs are related to
      various health-care settings where predisposing antibiotics are prescribed and C.
      difficile transmission occurs. Hospital-onset CDIs were prevented through an
      emphasis on infection control. IMPLICATIONS FOR PUBLIC HEALTH: More needs to be
      done to prevent CDIs; major reductions will require antibiotic stewardship along
      with infection control applied to nursing homes and ambulatory-care settings as
      well as hospitals. State health departments and partner organizations have shown
      leadership in preventing CDIs in hospitals and can prevent more CDIs by extending
      their programs to cover other health-care settings.

PMID- 22398845
TI  - Retroileal colorectal anastomosis: an old technique, still relevant.
AB  - Retroileal colorectal anastomosis is an infrequently used technique providing
      tension-free anastomosis after extended left-sided colonic resection, which was
      first described by Turnbull in 1972. The authors describe the use of a retroileal
      colorectal anastomosis in a patient with chronic Candida albicans and
      Enterococcal retroperitoneal abscess. The patient's condition was most likely
      secondary to an anastomotic leak and colonic fistula post en bloc resection for
      recurrence of a left renal cell carcinoma. After failure of antimicrobial therapy
      and percutaneous drainage, surgical intervention was required. This involved
      resection of the existing colocolonic anastomosis and drainage of the
      retroperitoneal abscess. A retroileal colorectal anastomosis was then necessary
      to ensure a tension-free anastomosis. To the best of our knowledge, this is the
      first reported case of retroileal anastomosis used for this purpose. It
      highlights the importance of this technique in the surgeon's armamentarium. 

PMID- 22398846
TI  - FDG-PET/CT-based gross tumor volume contouring for radiation therapy planning: an
      experimental phantom study.
AB  - As there is continuing controversy over the role of F-18-fluorodeoxyglucose (FDG)
      positron emission tomography (PET)/CT-fused imaging in radiation therapy (RT)
      planning, we performed a phantom study to assess the feasibility of FDG-PET/CT
      based gross tumor volume (GTV) contouring. The phantom set, consisting of an
      elliptical bowl and 6 spheres measuring from 10-37 mm in diameter, were filled
      with FDG to obtain 3 source-to-background ratios (SBRs) of 4, 8, and 16. The
      ratio to maximum intensity at 5% intervals was applied as the threshold for
      contouring. The ratio between contoured- and actual volumes (volume ratio) was
      calculated, and the threshold ratio was selected to provide a volume ratio close
      to 100%. To consider the clinical application, we applied the threshold value
      (maximum intensity * threshold ratio) for the largest 37-mm sphere to the 6
      spheres. The threshold ratio and the volume ratio in 6 spheres with 3 SBRs were
      compared using the Friedman test. Threshold ratios ranged from 25-80%; they were
      higher for smaller spheres (p = 0.003) and lower SBRs (p < 0.001). The volume
      ratios with the threshold value for the largest 37-mm sphere were lower in
      smaller spheres (p = 0.010). These results suggest that smaller lesions and
      higher background activities require a higher threshold ratio and smaller lesions
      a lower threshold value. FDG-PET/CT-fused imaging should not be used as a single
      modality but rather to obtain supplemental information in RT planning. The
      contoured GTV should be adjusted based on clinical data including conventional
      images.

PMID- 22398847
TI  - Innate immunity in the skin.

PMID- 22398848
TI  - Drug-induced movement disorders in children at paediatric emergency department:
      'dystonia'.
AB  - AIM: To examine cases with drug-induced dystonic reactions (DIDRs), to identify
      the complaints of the application, to classify the drugs causing those dystonic
      reactions (DRs) and to determine the treatment options and protective measures to
      prevent DIDRs. METHOD: The authors retrospectively analysed 55 cases with DIDRs
      at paediatric emergency department (PED) in a 5-year period. RESULTS: The mean
      age of the patients was 145.07+/-56.30 months, and of the 55 cases, 28 cases
      (50.9%) were boys. Antiemetics and antipsychotics were the most common causes of
      DIDRs. 35 (70%) patients developed DIDRs at therapeutic doses. Treatment side
      effect was the most common cause of the DIDRs (78.2%). The most common DIDRs were
      abnormal postures of the head and neck (56.6%). Laryngospasm was observed only in
      four cases (7.3%) that used either antipsychotics or psychostimulants. 51 (92.7%)
      children were treated with parenteral diphenhydramine successfully. CONCLUSION:
      Dystonia is a common side effect of certain drugs, even when therapeutic doses
      are administered. Although the most common DIDRs were abnormal postures of the
      head and neck, rare life-threatening conditions, may develop particularly due to
      use of antipsychotics. In treatment, diphenhydramine could effectively be used
      through parenteral way to eliminate the cholinergic effects of those drugs.
      However, the easiest and the safest way to prevent the development of DRs is to
      avoid unnecessary drug usage. In conclusion, physicians should be aware that
      antiemetic and antipsychotic drugs are associated with DRs in normal doses and
      that those drugs should be prescribed with a correct indication.

PMID- 22398849
TI  - Foreign field hospitals after the 2010 Haiti earthquake: how good were we?
AB  - OBJECTIVE: To assess the timing and activities of foreign field hospitals (FFH)
      deployed during the first month after the Haiti earthquake and to evaluate
      adherence to WHO/Pan American Health Organization (PAHO) guidelines. Results were
      compared with data from past sudden-onset disasters. METHODS: A systematic
      attempt was made to contact all relief actors within the health care sector
      involved in the 12 January through 12 February 2010 FFH deployment. This was done
      using an email-based questionnaire and a web survey. In addition, the authors
      undertook a literature review using PubMed and the Google search engine between
      March 2010 and May 2011. The authors contacted key informants and agencies
      identified by direct observations in the field by email or phone. RESULTS: A
      total of 44 FFH were identified. The first FFH was operational on day two post
      earthquake. The number of FFH beds peaked at about 3300 on day 17 post
      earthquake. During the first month, the authors estimate that FFH conducted no
      more than 12 000 major surgical operations. While 25% of the FFH adhered to
      either WHO/PAHO first essential deployment requirements, none followed both
      requirements of WHO/PAHO. Compared with the 2005 earthquake in Pakistan, twice as
      many FFH provided medical care, resulting in three times more FFH beds.
      CONCLUSIONS: The present study suggests that more FFH were sent to Haiti than to
      any previous sudden-onset disasters, but due to lack of data and transparency it
      remains impossible to determine to what extent did the first wave of FFH do any
      good in Haiti.

PMID- 22398850
TI  - Triage of pregnant women in the emergency department: evaluation of a triage
      decision aid.
AB  - BACKGROUND: Applying the Australasian Triage Scale to pregnant women presenting
      to emergency departments (EDs) is difficult as the descriptors may not reflect
      the urgency of the obstetric condition. This study aimed to examine whether
      condition-specific algorithms and triage education improved triage assessment and
      documentation of pregnant women presenting to the ED. METHOD: Algorithms with a
      decision aid for triage with minimum agreed descriptors were developed to triage
      two pregnancy conditions (pre-eclampsia and antepartum haemorrhage). Triage
      documentation was then audited before (n=50) and after (n=50) a triage education
      programme which introduced algorithms for both conditions. Significant
      differences were examined using chi(2) test with significance set at p<0.05.
      RESULTS: The quality of documentation of specific clinically significant symptoms
      of pre-eclampsia improved considerably, including the presence of headache from
      58% pre-education to 80% post-education (p=0.002), visual disturbances from 58%
      to 90% (p<0.001), epigastric pain from 24% to 80% (p=0.002) and the presence of
      fetal movements from 62% to 90% (p=0.001). Documentation of descriptors for
      vaginal bleeding >20 weeks gestation improved for estimation of blood loss from
      54% to 86% (p<0.001), patient 'appearance' from 32% to 62% (p=0.003) and,
      importantly, descriptions of patient's own assessment of their well-being from 8%
      to 28% (p=0.009). CONCLUSION: The introduction of triage education and condition
      specific decision aids for triage markedly improved triage assessment and
      documentation. The application of algorithms may reduce clinical risk resulting
      from suboptimal triage of pregnant women presenting to EDs.

PMID- 22398851
TI  - Decreased length of stay after addition of healthcare provider in emergency
      department triage: a comparison between computer-simulated and real-world
      interventions.
AB  - OBJECTIVE: (1) To determine the effects of adding a provider in triage on average
      length of stay (LOS) and proportion of patients with >6 h LOS. (2) To assess the
      accuracy of computer simulation in predicting the magnitude of such effects on
      these metrics. METHODS: A group-level quasi-experimental trial comparing the St.
      Louis Veterans Affairs Medical Center emergency department (1) before
      intervention, (2) after institution of provider in triage, and discrete event
      simulation (DES) models of similar (3) 'before' and (4) 'after' conditions. The
      outcome measures were daily mean LOS and percentage of patients with LOS >6 h.
      RESULTS: The DES-modelled intervention predicted a decrease in the %6-hour LOS
      from 19.0% to 13.1%, and a drop in the daily mean LOS from 249 to 200 min
      (p<0.0001). Following (actual) intervention, the number of patients with LOS >6 h
      decreased from 19.9% to 14.3% (p<0.0001), with the daily mean LOS decreasing from
      247 to 210 min (p<0.0001). CONCLUSION: Physician and mid-level provider coverage
      at triage significantly reduced emergency department LOS in this setting. DES
      accurately predicted the magnitude of this effect. These results suggest further
      work in the generalisability of triage providers and in the utility of DES for
      predicting quantitative effects of process changes.

PMID- 22398852
TI  - Survey of trainee attitudes to preparation for and participation in the FCEM
      examination.
AB  - INTRODUCTION AND AIMS: In the UK, specialist trainees in emergency medicine are
      required to pass the Fellowship of the College of Emergency Medicine (FCEM). This
      examination assesses clinical knowledge, attitudes and skills, management
      principles, critical appraisal, and the ability to search medical literature and
      synthesise information. The aims of this study were to ascertain what resources
      trainees felt were most valuable in preparation for the FCEM and to obtain
      trainee feedback on the running of the FCEM. METHODS: A questionnaire was
      developed in conjunction with the TSC into nine parts covering all aspects of
      preparation for and experience of sitting the FCEM. Email addresses of those
      trainees who had sat the FCEM examination in 2006 and 2007 were provided by the
      CEM and questionnaires were sent electronically to recipients. Responses were
      collated and analysed using Microsoft Excel. RESULTS: There was a response rate
      of 42% (86/203), of whom about three-quarters felt well prepared for the FCEM.
      The most highly valued resources for exam preparation were practice questions,
      private study and small group work. A yearly mock FCEM examination was felt to be
      important by those who had such access and local trainer involvement in exam
      preparation was perceived significant for success. CONCLUSIONS: Training
      programmes should make sure that facilities and expertise are available at a
      local level to allow trainees to have access to everything that is considered
      important in order to pass the FCEM.

PMID- 22398853
TI  - Lack of response to teriparatide therapy for bisphosphonate-associated
      osteonecrosis of the jaw.

PMID- 22398854
TI  - The burden of illness of osteoporosis in Canada.
AB  - To update the 1993 burden of illness of osteoporosis in Canada, administrative
      and community data were used to calculate the 2010 costs of osteoporosis at $2.3
      billion in Canada or 1.3% of Canada's healthcare expenditures. Prevention of
      fractures in high-risk individuals is key to decrease the financial burden of
      osteoporosis. INTRODUCTION: Since the 1996 publication of the burden of
      osteoporosis in 1993 in Canada, the population has aged and the management of
      osteoporosis has changed. The study purpose was to estimate the current burden of
      illness due to osteoporosis in Canadians aged 50 and over. METHODS: Analyses were
      conducted using five national administrative databases from the Canadian
      Institute for Health Information for the fiscal-year ending March 31 2008 (FY
      2007/2008). Gaps in national data were supplemented by provincial and community
      data extrapolated to national levels. Osteoporosis-related fractures were
      identified using a combination of most responsible diagnosis at discharge and
      intervention codes. Fractures associated with severe trauma codes were excluded.
      Costs, expressed in 2010 dollars, were calculated for osteoporosis-related
      hospitalizations, emergency care, same day surgeries, rehabilitation, continuing
      care, homecare, long-term care, prescription drugs, physician visits, and
      productivity losses. Sensitivity analyses were conducted to measure the impact on
      the results of key assumptions. RESULTS: Osteoporosis-related fractures were
      responsible for 57,413 acute care admissions and 832,594 hospitalized days in FY
      2007/2008. Acute care costs were estimated at $1.2 billion. When outpatient care,
      prescription drugs, and indirect costs were added, the overall yearly cost of
      osteoporosis was over $2.3 billion for the base case analysis and as much as $3.9
      billion if a proportion of Canadians were assumed to be living in long-term care
      facilities due to osteoporosis. CONCLUSIONS: Osteoporosis is a chronic disease
      that affects a large segment of the adult population and results in a substantial
      economic burden to the Canadian society.

PMID- 22398855
TI  - Burden of non-hip, non-vertebral fractures on quality of life in postmenopausal
      women: the Global Longitudinal study of Osteoporosis in Women (GLOW).
AB  - Among 50,461 postmenopausal women, 1,822 fractures occurred (57% minor non-hip,
      non-vertebral [NHNV], 26% major NHNV, 10% spine, 7% hip) over 1 year. Spine
      fractures had the greatest detrimental effect on EQ-5D, followed by major NHNV
      and hip fractures. Decreases in physical function and health status were greatest
      for spine or hip fractures. INTRODUCTION: There is growing evidence that NHNV
      fractures result in substantial morbidity and healthcare costs. The aim of this
      prospective study was to assess the effect of these NHNV fractures on quality of
      life. METHODS: We analyzed the 1-year incidences of hip, spine, major NHNV
      (pelvis/leg, shoulder/arm) and minor NHNV (wrist/hand, ankle/foot, rib/clavicle)
      fractures among women from the Global Longitudinal study of Osteoporosis in Women
      (GLOW). Health-related quality of life (HRQL) was analyzed using the EuroQol EQ
      5D tool and the SF-36 health survey. RESULTS: Among 50,461 women analyzed, there
      were 1,822 fractures (57% minor NHNV, 26% major NHNV, 10% spine, 7% hip) over 1
      year. Spine fractures had the greatest detrimental effect on EQ-5D summary
      scores, followed by major NHNV and hip fractures. The number of women with
      mobility problems increased most for those with major NHNV and spine fractures
      (both +8%); spine fractures were associated with the largest increases in
      problems with self care (+11%), activities (+14%), and pain/discomfort (+12%).
      Decreases in physical function and health status were greatest for those with
      spine or hip fractures. Multivariable modeling found that EQ-5D reduction was
      greatest for spine fractures, followed by hip and major/minor NHNV. Statistically
      significant reductions in SF-36 physical function were found for spine fractures,
      and were borderline significant for major NHNV fractures. CONCLUSION: This
      prospective study shows that NHNV fractures have a detrimental effect on HRQL.
      Efforts to optimize the care of osteoporosis patients should include the
      prevention of NHNV fractures.

PMID- 22398857
TI  - Role of complex defects in photocatalytic activities of nitrogen-doped anatase
      TiO(2).
AB  - Deep impurity states associated with a substitutional nitrogen at an oxygen site
      (N(O)) are believed to be the source of the visible-light absorption of nitrogen
      doped titanium dioxide (TiO(2)). Our comprehensive study using density functional
      theory (DFT) plus onsite Coulomb interaction (U) reveals that a titanium atom at
      an interstitial site (Ti(i)) is highly mobile and strongly binds with N(O).
      Hybridizations of N p with Ti d states of Ti(i) give rise to a new band at the
      valence band edge, eliminating the hole-trapping centers originated from the deep
      N(O) states. The suggested mechanism explains the photocatalytic oxidation
      reactions as well as the visible-light absorption observed on N-doped anatase
      TiO(2).

PMID- 22398856
TI  - Vitamin K supplementation for the primary prevention of osteoporotic fractures:
      is it cost-effective and is future research warranted?
AB  - Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to
      reduce fractures and increase survival in postmenopausal women. It would be a
      cost-effective intervention at commonly used thresholds, but high uncertainty
      around the cost-effectiveness estimates persists. Further research on the effect
      of vitamin K on fractures is warranted. INTRODUCTION: Vitamin K might have a role
      in the primary prevention of fractures, but uncertainties about its effectiveness
      and cost-effectiveness persist. METHODS: We developed a state-transition
      probabilistic microsimulation model to quantify the cost-effectiveness of various
      interventions to prevent fractures in 50-year-old postmenopausal women without
      osteoporosis. We compared no supplementation, vitamin D(3) (800 IU/day) with
      calcium (1,200 mg/day), and vitamin K(2) (45 mg/day) with vitamin D(3) and
      calcium (at the same doses). An additional analysis explored replacing vitamin
      K(2) with vitamin K(1) (5 mg/day). RESULTS: Adding vitamin K(2) to vitamin D(3)
      with calcium reduced the lifetime probability of at least one fracture by 25%,
      increased discounted survival by 0.7 quality-adjusted life-years (QALYs) (95%
      credible interval (CrI) 0.2; 1.3) and discounted costs by $8,956, yielding an
      incremental cost-effectiveness ratio (ICER) of $12,268/QALY. At a $50,000/QALY
      threshold, the probability of cost-effectiveness was 95% and the population
      expected value of perfect information (EVPI) was $28.9 billion. Adding vitamin
      K(1) to vitamin D and calcium reduced the lifetime probability of at least one
      fracture by 20%, increased discounted survival by 0.4 QALYs (95% CrI -1.9; 1.4)
      and discounted costs by $4,014, yielding an ICER of $9,557/QALY. At a
      $50,000/QALY threshold, the probability of cost-effectiveness was 80% while the
      EVPI was $414.9 billion. The efficacy of vitamin K was the most important
      parameter in sensitivity analyses. CONCLUSIONS: Lifetime supplementation with
      vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase
      survival in postmenopausal women. Given high uncertainty around the cost
      effectiveness estimates, further research on the efficacy of vitamin K on
      fractures is warranted.

PMID- 22398858
TI  - A combined pharmacometric analysis of dabigatran etexilate in healthy volunteers
      and patients with atrial fibrillation or undergoing orthopaedic surgery.
AB  - Dabigatran etexilate is the orally bioavailable pro-drug of dabigatran, a direct
      thrombin inhibitor. Using data from eight clinical studies in healthy volunteers
      and patients with non-valvular atrial fibrillation (AF) or undergoing orthopaedic
      surgery (OS), population pharmacokinetic (PK) and pharmacodynamic (PD) models
      were developed to investigate whether the PK and PD of dabigatran differ across
      different populations. In both healthy volunteers (n=80) and patients (n=1,965),
      the PK of dabigatran was best described by a two-compartment disposition model
      with first-order absorption and elimination. Renal function was the only
      covariate shown to have a clinically relevant impact on dabigatran exposure. The
      patient PK model was successfully applied in predicting exposure observed in the
      RE-LY trial evaluating dabigatran treatment in patients with non-valvular AF. The
      relationship between dabigatran plasma concentrations and activated partial
      thromboplastin time in healthy volunteers and patients (n=762) was best described
      with a combination of a linear model and a maximum effect (Emax) model,
      consistent with previous reports. PK/PD relationships were robust across the
      various populations tested and were not affected by any of the covariates
      examined. In summary, the PK of dabigatran is sufficiently consistent to allow
      extrapolation of data generated in healthy volunteers to patients with AF or
      undergoing OS.

PMID- 22398859
TI  - Restriction endonucleases: natural and directed evolution.
AB  - Type II restriction endonucleases (REs) are highly sequence-specific compared
      with other classes of nucleases. PD-(D/E)XK nucleases, initially represented by
      only type II REs, now comprise a large and extremely diverse superfamily of
      proteins and, although sharing a structurally conserved core, typically display
      little or no detectable sequence similarity except for the active site motifs.
      Sequence similarity can only be observed in methylases and few isoschizomers. As
      a consequence, REs are classified according to combinations of functional
      properties rather than on the basis of genetic relatedness. New alignment
      matrices and classification systems based on structural core connectivity and
      cleavage mechanisms have been developed to characterize new REs and related
      proteins. REs recognizing more than 300 distinct specificities have been
      identified in RE database (REBASE: http://rebase.neb.com/cgi-bin/statlist ) but
      still the need for newer specificities is increasing due to the advancement in
      molecular biology and applications. The enzymes have undergone constant evolution
      through structural changes in protein scaffolds which include random mutations,
      homologous recombinations, insertions, and deletions of coding DNA sequences but
      rational mutagenesis or directed evolution delivers protein variants with new
      functions in accordance with defined biochemical or environmental pressures.
      Redesigning through random mutation, addition or deletion of amino acids,
      methylation-based selection, synthetic molecules, combining recognition and
      cleavage domains from different enzymes, or combination with domains of
      additional functions change the cleavage specificity or substrate preference and
      stability. There is a growing number of patents awarded for the creation of
      engineered REs with new and enhanced properties.

PMID- 22398860
TI  - L-pantoyl lactone dehydrogenase from Rhodococcus erythropolis: genetic analyses
      and application to the stereospecific oxidation of L-pantoyl lactone.
AB  - The 1,2-propanediol (1,2-PD) inducible membrane-bound L-pantoyl lactone (L-PL)
      dehydrogenase (LPLDH) has been isolated from Rhodococcus erythropolis AKU2103
      (Kataoka et al. in Eur J Biochem 204:799, 1992). Based on the N-terminal amino
      acid sequence of LPLDH and the highly conserved amino acid sequence in homology
      search results, the LPLDH gene (lpldh) was cloned. The gene consists of 1,179
      bases and encodes a protein of 392 amino acid residues. The deduced amino acid
      sequence showed high similarity to the proteins of the FMN-dependent alpha
      hydroxy acid dehydrogenase/oxidase family. The overexpression vector pKLPLDH
      containing lpldh with its upstream region (1,940 bp) was constructed and
      introduced into R. erythropolis AKU2103. The recombinant R. erythropolis AKU2103
      harboring pKLPLDH showed six times higher LPLDH activity than the wild-type
      strain. Conversion of L-PL to ketopantoyl lactone was achieved with 92% or 80%
      conversion yield when the substrate concentration was 0.768 or 1.15 M,
      respectively. Stereoinversion of L-PL to D-PL was also carried out by using the
      combination of recombinant R. erythropolis AKU2103 harboring pKLPLDH and
      ketopantoic acid-reducing Escherichia coli.

PMID- 22398861
TI  - Absence of sterols constrains food quality of cyanobacteria for an invasive
      freshwater bivalve.
AB  - The accumulation of cyanobacterial biomass may severely affect the performance of
      aquatic consumers. Here, we investigated the role of sterols in determining the
      food quality of cyanobacteria for the invasive clam Corbicula fluminea, which has
      become a common benthic invertebrate in many freshwater ecosystems throughout the
      world. In standardized growth experiments, juvenile clams were fed mixtures of
      different cyanobacteria (Anabaena variabilis, Aphanothece clathrata,
      Synechococcus elongatus) or sterol-containing eukaryotic algae (Cryptomonas sp.,
      Nannochloropsis limnetica, Scenedesmus obliquus). In addition, the cyanobacterial
      food was supplemented with different sterols. We provide evidence that somatic
      growth of C. fluminea on cyanobacterial diets is constrained by the absence of
      sterols, as indicated by a growth-enhancing effect of sterol supplementation.
      Thus, our findings contribute to our understanding of the consequences of
      cyanobacterial mass developments for benthic consumers and highlight the
      importance of considering sterols as potentially limiting nutrients in aquatic
      food webs.

PMID- 22398862
TI  - A new platform to become the forefront in the latest developments of experimental
      surgery.

PMID- 22398863
TI  - Significance of lymph node micrometastasis in pancreatic cancer patients.
AB  - BACKGROUND /AIMS: The present study deals with the significance of lymph node
      micrometastasis in the survival rate for pancreatic cancer patients. METHODS:
      Between January 2006 and December 2010 at the First Department of Surgery in
      Kosice, a prospective trial was done in which we investigated the survival rate
      after radical pancreatic resection. All negative lymph nodes removed during
      standard radical lymphadenectomy were subjected to immunohistochemical staining
      to detect occult micrometastasis. A comparison of the median survival rate in
      groups of patients with immunohistochemistry-positive and -negative lymph nodes
      was performed. RESULTS: Radical pancreatic resection with standard radical
      lymphadenectomy was performed on 64 pancreatic cancer patients. The median
      survival time was 15 months. Out of the 319 histopathologically negative lymph
      nodes (34 patients), 134 lymph nodes were classified as immunohistochemistry
      positive (21 patients). The median survival rate in the group of patients with
      immunohistochemistry-negative lymph nodes was 23 months, but in the group of
      patients with immunohistochemistry-positive lymph nodes it was 14 months. There
      was a statistically significant difference between these 2 groups of patients (p
      <= 0.01). CONCLUSION: The immunohistochemical examination of histopathologically
      negative lymph nodes can lead to positive lymph node detection. The presence of
      lymph node micrometastasis could predict the survival rate.

PMID- 22398865
TI  - Turning back time.
AB  - I've spent an hour with Paula giving her much-needed support. She feels burnt out
      and utterly demoralised. She's counting the days towards retirement, and then she
      drops the bombshell. She's six younger than I am. She leaves, thanking me for
      listening, and saying: 'If I had my life over again I'd do it do differently.
      Wouldn't you?'

PMID- 22398864
TI  - [Spontaneous bacterial peritonitis].
AB  - Spontaneous bacterial peritonitis (SBP) is the most frequent infection in
      patients with cirrhosis during hospitalization and is associated with high acute
      and long-term mortality. Diagnosis is made by paracentesis with determination of
      neutrophil count in ascitic fluid. Empirical antibiotic therapy must be initiated
      immediately. The choice of drug is dependent on prior therapies. Liver
      transplantation has to be considered in the absence of contra-indications.
      Prophylaxis of SBP is indicated in patients with ascites and gastrointestinal
      hemorrhage, and in patients after SBP. Primary prophylaxis should be considered
      in high-risk patients with cirrhosis and ascites. The development of resistance
      to antibiotic drugs is a relevant side-effect.

PMID- 22398866
TI  - Rehabilitation needs following stoma formation: a patient survey.
AB  - This article reports the findings from a patient survey which examined
      rehabilitation needs following stoma formation at an acute NHS trust within
      Greater London. Of the 203 questionnaires sent, 100 were returned (49% response
      rate). Two-thirds of the sample (71%) reported experiencing stoma-related
      complications, and a third of the sample (33%) experienced difficulties receiving
      their stoma prescriptions on time. Information and support requirements were
      reported to be most acute during the first six weeks following discharge.
      Additionally, return to work was a major transition for those of working age,
      testing their physical health and social confidence. Accessible specialist
      support is essential during the first few weeks of this rehabilitation process
      and much perceived benefit is gained from continued nursing support in the
      community.

PMID- 22398867
TI  - Looking after everyone except yourself: the double-edged sword of caring.
AB  - Caring is, in a broad sense, a basic phenomenon of human life (Benner and Wrubel,
      1989; Noddings 1999) and an intrinsic part of what it is to be human. In other
      words, human beings may not consciously choose to care, but caring is inherent in
      them: it is an activity encountered beyond the boundaries of nursing, and
      certainly not unique to nursing or to the overtly 'caring' services, such as
      palliative care provision in the community, hospitals and hospices.

PMID- 22398868
TI  - Sexually transmitted infections in older people: the community nurse's role.
AB  - Sexual health is complex and applies to everyone. Sexual ill health can have
      negative outcomes for individuals, communities and the country in terms of costs,
      as well as the impact it can have on a person's health and wellbeing. STIs are an
      important source of sexual ill health, but can be prevented by education and
      promotion of safer sex practices. One essential aspect of the role of the
      community nurse is to promote health; community nurses have an obvious and
      clearly defined public health role. The challenges faced by the older person with
      regards to their sexual health need to be acknowledged and actions, devised and
      implemented, that will engage them. This article discusses some of the issues
      that older people may face with regards to their sexual health. A resource list
      is provided.

PMID- 22398869
TI  - Effective mentoring in the community setting.
AB  - As nurses, we are expected to demonstrate the linking of theory to practice,
      undertake continuous assessment and to facilitate reflective practice. Literature
      suggests that the majority of mentors feel unprepared for the role and lack
      confidence in their ability to support students (Duffy, 2004). The main
      challenges facing mentors are understanding the needs of each individual and
      adapting and developing strategies in order to support them effectively. Whilst
      there is a major cognitive / intellectual component to mentorship both student
      and mentor often experience difficulties with these aspects of their roles
      (Moseley and Davies, 2008). By recognizing the need to gain insight into the
      students individual needs mentors will be able to identify any concerns and
      develop action plans in order to alleviate them.

PMID- 22398870
TI  - An insight into continence management in patients with dementia.
AB  - This article discuses the prevalence of urinary and faecal incontinence in people
      with dementia. The content explores the physiological changes affecting the older
      bladder and bowel together with the psychological and behavioural problems
      associated with dementia that impact on continence.

PMID- 22398871
TI  - Using referral guidelines to support best care outcomes for patients.
AB  - District nurses play a pivotal role in individuals' care pathways by meeting
      their needs in the community. However, district nurses are frequently referred
      patients for whom other interprofessional colleagues have more suitable skills to
      help in achieving their optimum care outcome. Various major reports have
      identified a clear need to define what district nurses do and how they will
      respond appropriately to patients' needs. However, there remains only tacit
      understanding of district nurse referral criteria across the country and within
      community organizations. This article discusses how a set of facilitative
      district nurse referral guidelines have been devised to support individuals in
      achieving their best care outcome. We also debate approaches to managing
      referrals to district nursing services and the pressing need to ensure these are
      effectively managed in practice.

PMID- 22398872
TI  - Consent to care: patients who demand or refuse treatment.
AB  - For district nurses obtaining consent is, in most cases, a routine part of
      delivering care and treatment to patients. In some cases, however, patients will
      have strong views on the type of treatment they want for their condition and
      demand it be provided, or equally strong views that they want no treatment and
      refuse consent. In this article Richard Griffith and Cassam Tengnah consider the
      legal and professional obligations of district nurses faced with patients who
      demand or refuse treatment.

PMID- 22398873
TI  - Will HEE and LETBs deliver the 'right nurse'?
AB  - The restructuring of the NHS in England will see the loss of strategic health
      authorities, with their workforce education remit being transferred to a
      completely new structure comprising Health Education England (HEE) and Local
      Education and Training Boards (LETBs). HEE will provide national oversight of
      strategic workforce planning and allocate the education and training budget, and
      will also be responsible for national schemes like junior doctor training. The
      LETBs will be populated by representatives of health-care providers and
      professionals, and will be the interface with HEE. They will be charged with
      ensuring high-quality outcomes from educational investment and meeting the needs
      of health-care delivery, patients and the public. The universities, colleges,
      employers and other local education providers will remain responsible for
      educating the health-care workforce.

PMID- 22398874
TI  - Promotion effects of optical antipodes on the formation of helical fibrils:
      chiral perfluorinated gelators.
AB  - A chiral gelator, RR- or SS-N,N'-diperfluorooctanoyl-1,2-diaminocyclohexane,
      gelated racemic 2-butanol. The gel was most stable at the racemic mixture, its
      stability lowered with the increase in the optical purity of the gelator.
      Notably, characteristic helically coiled fibrils were formed in the narrow region
      of enantiomer excess (ee = 0.2-0.4). Promotion effects of the antipodal
      enantiomers are proposed.

PMID- 22398876
TI  - Prolonged viral RNA detection in the central nervous system of one-week-old Swiss
      albino mice following coxsackievirus B4 and echovirus 9 infection.
AB  - OBJECTIVES: Type B coxsackieviruses (CV-B), together with echoviruses (E), are
      among the most common pathogens encountered in aseptic meningitis and
      meningoencephalitis. They frequently infect the central nervous system (CNS). The
      mechanisms of virus spreading in the CNS are poorly understood. In the present
      study, we investigated CV-B4 and E-9 spreading and neurotropism within
      intraperitoneally inoculated one-week-old Swiss albino mice. METHODS: Seminested
      RT-PCR and virus isolation were used to assay viral distribution. RESULTS: Viral
      RNA was present in various organs: brain, spinal cord, spleen and heart at
      various times post-infection (p.i.); ranging from 1 day p.i. up to 30, 60 and 90
      days p.i, respectively, for CV-B4-JVB-, E-9 Barty- and CV-B4-E2-infected mice.
      Organs became negative for virus isolation after 5 days p.i., except for brain
      and heart from CV-B4 E2-infected mice, which remained positive for up to 10 and
      15 days p.i., respectively. Negative viral RNA strand was detected mainly in
      brain and spinal cord of infected mice until 30 and 60 days p.i. CONCLUSION: This
      is the first report on the persistence of CV-B4 and E-9 in the CNS of
      intraperitoneally inoculated mice.

PMID- 22398875
TI  - Huntington's disease from the patient, caregiver and physician's perspectives:
      three sides of the same coin?
AB  - The aim of this study was to identify determinants of functional disability,
      patient's quality of life (QoL) and caregivers' burden in Huntington's disease
      (HD). Eighty HD patients participated in the study. Motor and behavioral
      disturbances as well as cognitive impairment were assessed using motor,
      behavioral and cognitive parts of the Unified Huntington Disease Rating Scale
      (UHDRS); Hamilton Depression Rating Scale was used to assess depression.
      Disability, health-related QoL and the impact of the disease on the caregivers
      were assessed using the following methods: UHDRS Functional Assessment Score, SF
      36 Scale and Caregiver Burden Inventory. Multiple regression analysis showed that
      motor disturbances, cognitive impairment, apathy and disease duration were the
      independent predictors of disability. Depression and cognitive disturbances were
      the determinants of patient's QoL, while motor disturbances and depression were
      the predictors of the caregiver burden. Patient's disability and QoL as well as
      caregivers' burden should be taken into consideration while planning treatment
      strategy and the results of the present study show that the predictors of those
      treatment targets are different.

PMID- 22398877
TI  - Rapid differentiation of Candida dubliniensis from Candida albicans by early D
      xylose assimilation.
AB  - OBJECTIVE: To determine if D-xylose (XYL) and/or alpha-methyl-D-glucoside (MDG)
      assimilation can be used reliably as a rapid test to differentiate Candida
      dubliniensis from Candida albicans at an earlier time point such as 2 h after
      inoculation. MATERIALS AND METHODS: Thirty isolates of C. albicans and C.
      dubliniensis recovered from anatomical sites and clinical specimens were used.
      Isolates were inoculated into the API 20C AUX yeast identification system, and
      incubated at 30 degrees C. XYL and MDG assimilations were read at 2-hour
      intervals beginning 2 h after the initial inoculation and up to 24 h of
      incubation; thereafter, results were read after 48 and 72 h. RESULTS: Twenty-nine
      (97%) C. albicans isolates had assimilated XYL at 16 h and, by 24 h, all isolates
      were positive for XYL assimilation. None of the C. dubliniensis isolates
      assimilated XYL. The MDG assimilation revealed that 24, 40, 92 and 100% of C.
      albicans isolates became positive after 16, 24, 48 and 72 h of incubation,
      respectively, whereas only 3% of C. dubliniensis isolates assimilated MDG after
      72 h. CONCLUSIONS: The findings showed that it is possible to rapidly
      differentiate C. albicans from C. dubliniensis isolates using the API 20C AUX
      carbohydrate assimilation kits after 16 h of incubation at 30 degrees C based on
      the XYL assimilation.

PMID- 22398879
TI  - Realization of a salt bridge-free microfluidic reference electrode.
AB  - We report on the design of a microfluidic electrochemical cell with a true
      Ag/AgCl reference electrode that does not rely on a physical barrier or salt
      bridge, but instead takes advantage of slow diffusion times in micro-channels.
      The device concept is demonstrated in PDMS using the Ir(+IV)/Ir(+III) redox
      couple as an example. A scaling analysis provides limits of operation for the
      device.

PMID- 22398878
TI  - Molecular analysis and genotype-phenotype correlation in patients with
      antithrombin deficiency from Southern Italy.
AB  - We sequenced the SERPINC1 gene in 26 patients (11 males) with antithrombin (AT)
      deficiency (22 type I, 4 type II), belonging to 18 unrelated families from
      Southern Italy. Heterozygous mutations were identified in 15/18 (83.3%) families.
      Of them, eight were novel mutations, each being identified in one family. Seven
      clearly cause impaired protein synthesis (four frameshift, one non-stop, one
      splicing and one 21bp deletion). One, present in a single patient, is a missense
      mutation thought to be causative because: a) it is absent in 100 chromosomes from
      controls; b) it involves a highly conserved amino acid, whose change is predicted
      to impair AT activity; c) no other mutation is present in the propositus. Severe
      mutations (i.e. nonsense, frameshift, deletions) were invariably identified in
      type I patients. In type II patients, 3/4 were missense mutations; the fourth
      leads to a 19 nucleotides shift in the stop codon. In addition to the type of
      mutation, the co-existence of other predisposing factors in most patients helps
      explain the severity of the present type I cases (age at first event, recurrence
      during prophylaxis). In the five families in which there was more than one member
      affected, the same genotype and a concordant clinical expression of the disease
      were found. We conclude that the molecular bases of AT deficiency in Southern
      Italy are different as compared to other geographic areas, and that molecular
      analysis and the study of the effect of the mutation may help predict the
      clinical expression of the disease.

PMID- 22398880
TI  - A blind randomized controlled trial of cognitive versus behavioral versus
      cognitive-behavioral therapy for patients with rheumatoid arthritis.
AB  - BACKGROUND: Despite evidence that cognitive-behavioral therapy (CBT) is effective
      for rheumatoid arthritis (RA), little is known about which components of therapy
      are most efficacious. The present study compared the efficacy of CBT with
      cognitive therapy (CT) and behavioral therapy (BT) for patients with RA. We
      hypothesized that CBT would be more efficacious on a broader range of outcomes.
      METHODS: Participants (n = 104) with classic or definite RA were randomized to
      receive one of three active treatments (CBT, CT or BT) or a wait-list control
      (WLC). Participants were assessed at baseline, post-treatment and 6 months on a
      range of outcomes. Measures of disease activity, joint function, disability and
      psychological functioning were included. RESULTS: The results showed that
      participants who received cognitive components had greater improvements in tender
      joint counts and C-reactive protein at post-treatment. Those receiving either BT
      or CT alone improved more on anxiety than CBT or WLC. At 6 months, the three
      active treatment groups could only be distinguished on tender joints, which
      favored CT and CBT. CONCLUSIONS: CBT did not demonstrate the broader benefits to
      patients that we expected, nor was there evidence that BT produced effects that
      were superior to CT alone. CT was superior to at least one of the other two
      active treatment components on 3 of the 7 outcome measures at post-treatment.
      Effect sizes for the interventions that included cognitive components were
      similar to those reported in the literature. These results suggest that CT is an
      effective treatment for RA and need not necessarily include behavioral
      strategies.

PMID- 22398881
TI  - The efficacy and safety of high-dose arbekacin sulfate therapy (once-daily
      treatment) in patients with MRSA infection.
AB  - The efficacy and safety of once-daily high-dose arbekacin sulfate therapy for
      methicillin-resistant Staphylococcus aureus (MRSA) infection were evaluated, with
      analysis of their relationship to blood drug levels. The study was conducted in
      patients with pneumonia or sepsis, the cause of which was suspected to be MRSA,
      who were admitted to the Nagasaki University Hospital or its affiliated hospitals
      between January 2009 and December 2010. The initial drug dose was set at a level
      expected to yield the goal peak of 20 MUg/ml and a trough level of less than 2
      MUg/ml, using the Habekacin Therapeutic Drug Monitoring analysis software.
      Thirteen patients were enrolled: 10 patients had pneumonia and 3 patients had
      sepsis. Patient mean age was 72.0 years; mean initial drug dose was 269.2 mg.
      Clinical efficacy at completion of treatment and bacterial eradication-reduction
      were achieved in 66.7% (6/9) and 62.5% (5/8) of patients, respectively. Incidence
      of adverse reactions was 38.5% (5/13). In analysis of efficacy in relationship to
      serum drug levels, the peak drug level was 22.7 +/- 5.50 MUg/ml, on average, and
      15 MUg/ml or higher in all 6 responders. Also, in patients with renal
      dysfunction, it seemed to be essential to ensure a certain peak drug level and to
      control the trough level appropriately. Although the number of patients was
      limited, once-daily high-dose arbekacin sulfate therapy may be highly effective,
      without posing any major safety problems. Further larger-scale studies are
      needed.

PMID- 22398882
TI  - Tuberculous otitis media with endobronchial tuberculosis.
AB  - Although tuberculosis can affect various organs and tissues, the lung is the site
      most commonly involved. Extrapulmonary tuberculosis (EPTB) involves relatively
      inaccessible and variable sites and is consequently often overlooked by
      clinicians. The ear is a notably very rare site of EPTB, and the diagnosis is
      difficult because of the variable and confusing signs and symptoms. To our
      knowledge, this is the first case in which tuberculous otitis media and
      endobronchial tuberculosis coexisted.

PMID- 22398883
TI  - Genital herpes zoster as a consequence of cancer chemotherapy-induced
      immunosuppression: report of a case.
AB  - Herpes zoster (HZ) is a clinical manifestation of the reactivation of the
      varicella zoster virus (VZV). HZ of the male genital area is a rarely reported
      condition. The exact mechanism of latency and reactivation of VZV in these
      patients is unknown. The incidence of HZ can be associated with various
      conditions such as malignancies, immune deficiencies, autoimmune diseases,
      psychological conditions, and human immunodeficiency infection or HIV disease. In
      this report, we describe a rare case of HZ on male genitalia following the
      administration of immunosuppressant drugs for bowel cancer. The patient developed
      classical features of HZ during chemotherapy, 2 years after the initial
      chemotherapy for his bowel cancer. The ulcers of HZ lesions were treated with
      chlorhexidine (Curasept) ointment to prevent secondary bacterial infection. All
      the lesions subsided gradually and in 2 weeks with no later symptoms or pain.
      Genitalia are an unusual site of eruption in HZ. Patients with malignancy and
      iatrogenic immunodeficiency have an increased risk of reactivation of VZV and
      development of HZ.

PMID- 22398884
TI  - In these pages....

PMID- 22398885
TI  - With Ferenczi, the contemporary psychoanalyst is other.
AB  - Ferenczi's main interests centered on the clinical situation, and through them he
      felt the need to reformulate, discard and expand many aspects of existing theory
      to the extent that, in my opinion, he succeeded in constructing a specifically
      Ferenczian metapsychological conception. After briefly outlining the essentials
      of Ferenczi's theoretical concepts-highlighting above all the importance given to
      the interaction with others in psychic configuration and functioning-I go the
      opposite way, in a "mutatis mutandis" game, "deducing", as though they did not
      already exist and had to be invented, the technical and clinical approaches
      implied by this said metapsychology once it is constructed. One conclusion is
      that a psychoanalysis in tune with Ferenczi's conceptions is different from the
      one that ruled in the last century and in which a preferably solipsistic reading
      of Freud was dominant. Moreover, due to reasons that I will attempt to explain,
      today's psychoanalyst must stop thinking of himself as an absence (this is how I
      see the so-called "cure type" and others similar to it), and operate as a true
      other in a vivid relation with the patient.

PMID- 22398886
TI  - Mutuality: clinical and metapsychological potentials of a failed experiment.
AB  - Ferenczi's experiments with mutual analysis are often dismissed, without
      acknowledging the results obtained from them and his own cautionary remarks about
      their limits. Though ultimately failed, Ferenczi's experiments with mutual
      analysis were a source of clinical and metapsychological knowledge, despite the
      fact that he was unable to elaborate them in his lifetime. In this paper I
      connect mutuality to the development of the psyche, especially to the
      constitutive core of the intrapsychic. To understand the latter, it is necessary
      to take into account, among others, issues such as the common attribute, the
      mutual flux between the unconsciouses, the dialogue of unconsciouses, the
      maternal profundity, the primal relationship with the mother, and, above all, the
      primal unity between mother and child, which are fundamental for the emergence
      and development of the primary psychic forces. Incidences of rupture, distortion
      of the core of mutuality in the psychic life, its loss and disadjustment, by
      means of external traumatizing forces, and some clinical implications are
      described.

PMID- 22398887
TI  - From disavowal and murder to liberty.
AB  - In his (1909) paper, Introjection and Transference, Ferenczi puts forward the
      murder that, at the end, has to be inevitably repeated with the patient. This
      idea is particularly pertinent to patients who are victims of transgenerational
      traumas and their disavowal. The capacity to talk and even to think is paralyzed
      when a family history is made of emptiness, murder and madness. The case of an
      interminable analysis allows us to grasp how trauma and its disavowal are
      reenacted in the transference and in the countertransference. The patient comes
      to analysis searching for meaning in the face of something that could not be
      elaborated and remains meaningless. Interpretation and construction open the way
      to a process of historicization/subjectivation that is essential to access
      temporalization and to open up a future that might escape the repetition of a
      disavowed and timeless past.

PMID- 22398888
TI  - Sandor Ferenczi: from clinical turmoil to theoretical articulations.
AB  - The article deals with concepts proposed by Sandor Ferenczi: confusion of
      tongues, disavowal and progressive trauma, illustrated by a clinical example, in
      which excessive life experiences deeply determined the psychic construction,
      compromising the integrity of the self-image and the potentiality of egoic
      capacities. We attempt to understand the uniqueness of the patient's history, and
      the ethical practice of deep analytic listening.

PMID- 22398889
TI  - The fear of turning into dust: notes on a group for sexually abused women.
AB  - For 10 years, I have been responsible for a group for adults who were sexually
      abused during childhood. In this brief paper, I will analyze one aspect of the
      particular kind of identification that exists between a child and an abusing
      adult, using Bion's concept of valency and Kaes' theories of unconscious
      alliances and pacts, in an attempt to further qualify Ferenczi's concept of
      identification with the aggressor. I will then show how the group encourages the
      process of disidentification with the aggressor.

PMID- 22398890
TI  - Introduction to "No more away: techno-attachments and the relational future" by
      Christina R. Griffin Ph.D.

PMID- 22398891
TI  - No more away: techno-attachments and the relational future.
AB  - This paper speculates about the impact of techno-connectedness on our children,
      ourselves, our grandchildren. Triggered by recollections from Victorian novels
      that describe European summers "away" from home, a concern about loss of
      opportunity, the "space" for self-discovery in this young generation will be
      explored in a relational context. Brought about by pervasive dependence upon
      computer technology, is self-experience fragmented and attachment changed by the
      ubiquitous technological presence and is the more isolated, reflective experience
      being eroded?

PMID- 22398892
TI  - Shifting sexual cultures and the problem and promise of psychoanalytic ideals.

PMID- 22398893
TI  - From Oedipus complex to Oedipal complexity: reconfiguring the negative Oedipus
      complex and the disowned erotics of disowned sexualities.

PMID- 22398898
TI  - Corpus callosotomy with the CO2 laser suction device: a technical note.
AB  - INTRODUCTION: Patients with symptomatic generalized epilepsy who are not
      candidates for resections may be considered for corpus callosotomy. METHODS: The
      two patients who were followed in this series underwent resection of the corpus
      callosum utilizing the OmniGuide CO(2) Laser System. SURGICAL TECHNIQUE: The
      OmniGuide CO(2) Laser Systemcan be used in place of the bipolar electrocautery in
      a corpus callosotomy to improve midline dissection, decrease the likelihood of
      entering the ventricle, and improve visualization in the dissection. CONCLUSION:
      The OmniGuide CO(2) Laser System is a valuable option when performing a corpus
      callosotomy.

PMID- 22398899
TI  - [Recent approaches of personalized medicine for inflammatory bowel disease].

PMID- 22398900
TI  - [Mechanism and therapeutic strategy of second failure of infliximab treatment for
      Crohn's disease].

PMID- 22398901
TI  - [New therapeutic strategy for patients with Crohn's disease using of adalimumab].

PMID- 22398902
TI  - [The efficacy of GMA therapy in Crohn's disease].

PMID- 22398903
TI  - [Endoscopic balloon dilation of intestinal strictures in Crohn's disease].

PMID- 22398904
TI  - [Classification of the bleeding pattern in colonic diverticulum is useful to
      predict the risk of bleeding or re-bleeding after endoscopic treatment].
AB  - We examined the re-bleeding rate after endoscopic hemostasis according to the
      bleeding pattern in patients with an acute lower gastrointestinal hemorrhage from
      colonic diverticula in 34 patients with active bleeding (Type 1) and 49 patients
      with exposed vessels and/or erosions in the base of diverticulum and no active
      bleeding (Type 2). Endoscopic hemostasis was performed by clipping the exposed
      vessel or erosions (direct method) or the entire diverticular orifice (reefing
      method). The incidence of re-bleeding was significantly higher in the Type 1
      group than in the Type 2 group (p=0.002). All Type 1 cases were treated by the
      reefing method. In contrast, 14 of the 49 Type 2 cases were treated by the direct
      method, and no re-bleeding was observed in these cases. Of the other 35 Type 2
      cases treated by reafing, rebleeding was seen in 5 cases. More effective
      endoscopic treatment is needed to prevent early re-bleeding, especially for Type
      1 patients. The direct method may therefore reduce the rate of re-bleeding in
      Type 2 patients.

PMID- 22398905
TI  - [A very elderly case of complete remission by chemotherapy in a patient of
      primary esophageal non-Hodgkin lymphoma].
AB  - A very elderly patient with primary non-Hodgkin lymphoma of the esophagus is
      reported. An 87-year-old woman presented with dysphagia. Endoscopy revealed an
      elevated lesion with ulceration in the middle and lower esophagus. Endoscopic
      biopsy demonstrated pathological diagnosis and immunochemistry typical of non
      Hodgkin lymphoma (Ann Arbor stage IIIEA), diffuse large B-cell lymphoma on the
      WHO classification. Systemic chemotherapy with 6 courses of a 50% dose of R-CHOP
      followed by 8 courses of rituximab for maintenance, successfully resulted in
      complete remission. Complete remission has been maintained for 58 months.

PMID- 22398906
TI  - [Different sensitivity to chemotherapy between adenocarcinoma and adenosquamous
      carcinoma in a case of synchronous multicentric gastric cancer].
AB  - A 60-year-old man presented with upper gastrointestinal bleeding. We diagnosed
      double gastric cancer (adenocarcinoma and adenosquamous carcinoma) based on an
      endoscopic examination. Due to uncontrollable bleeding, total gastrectomy was
      performed after 4 courses of chemotherapy with S-1+cisplatin. Histological
      investigation revealed that no obvious anti-cancer effect was observed in
      adenosquamous carcinoma (Grade 1), while tumor cells were eliminated in the area
      of adenocarcinoma (Grade 3). This case clearly demonstrated that sensitivity to
      chemotherapy was different between adenocarcinoma and adenosquamous carcinoma of
      the stomach.

PMID- 22398907
TI  - [Recurrent gastric volvulus resolved surgically after therapeutic percutaneous
      endoscopic gastrostomy in Duchenne muscular dystrophy].
AB  - A 20-year-old man with Duchenne muscular dystrophy (DMD) with recurrent gastric
      volvulus underwent percutaneous endoscopic gastrostomy (PEG). Four months later,
      he developed vomiting and consciousness disturbance. CT revealed gastric volvulus
      recurrence along the gastrostomy axis. Endoscopic repositioning failed and
      fistula perforation necessitated emergency surgery. The upper position of the
      stomach was twisted counter-clockwise and revolved on the gastrostomy axis
      sliding between the lower stomach and abdominal wall. The fistula showed necrotic
      perforation and was thus resected. The anterior stomach wall was fixed to the
      abdominal wall at 3 triangular points. Thereafter, gastric volvulus did not
      recur. PEG is reportedly effective for preventing gastric volvulus, but there are
      rare cases of postgastrostomy recurrence. This successfully managed case provides
      valuable clinical insights.

PMID- 22398908
TI  - [Two cases of circumferential rectal invasion from prostatic cancer].
AB  - We report two cases of prostatic cancer invading the rectum with circumferential
      rectal wall thickening. In both cases, reddish and uneven edematous mucosa was
      observed by colonoscopy and the boundary of the lesion was indistinct. No mass or
      ulcer formation was not observed. CT scan showed irregular prostatic swelling and
      circumferential rectal wall thickening adjacent to the prostate. The rectal
      biopsy specimen showed moderately to poorly differentiated adenocarcinoma, and it
      was positive on PSA immunostaining. Although rectal invasion of prostatic cancer
      is relatively rare, it is important to be aware that prostatic cancer can cause
      circumferential stenosis of the rectum.

PMID- 22398909
TI  - [A case of anorectal melanoma localized in mucosa].
AB  - The patient was a 67-year-old woman. An elevated rectal lesion had been
      identified at a local clinic, and colonoscopy revealed a 7-mm black elevated
      lesion with blackening of the surrounding mucosa. Malignant melanoma was
      diagnosed by biopsy, and the patient was referred to our department. An invasion
      depth of M was diagnosed on the basis of preoperative imaging. Local excision was
      considered, but abdominoperineal resection was performed in light of its nature,
      to perform curative resection. Pathological findings showed abnormal cells
      staining positive for HMB-45 in the tumor and surrounding mucosa, but these were
      localized within the mucosa. As of 1 year and 6 months after surgery, the patient
      has survived without recurrence.

PMID- 22398910
TI  - [A case report of pancreatic serous cystadenoma coexistent with adenosquamous
      carcinoma].
AB  - A 70-year-old man was admitted to our hospital because a mass was incidentally
      found in the body of the pancreas. The mass was suspected to be serous
      cystadenoma from the findings of abdominal enhanced computed tomography, magnetic
      resonance imaging and endoscopic ultrasonography. In addition, another solid mass
      was detected in the pancreatic head on imaging tests. Magnetic resonance
      cholangiopancreatography and endoscopic retrograde cholangiopancreatography
      showed stenosis both of the main pancreatic duct at the head and bile duct, but
      the brushing cytology of the bile duct at ERCP showed no malignant cells.
      However, the findings of several examinations strongly suggested the coexistence
      of a serous cystadenoma and a pancreatic cancer, therefore we conducted spleen
      preserving total pancreatectomy, and the pathological findings of the resected
      specimen showed serous cystadenoma coexistence with pancreatic adenosquamous
      carcinoma.

PMID- 22398911
TI  - [A case of malignant peritoneal mesothelioma successfully treated with systemic
      chemothrapy].
AB  - A 64-year-old man with a 2-month history of abdominal distension was admitted for
      transient cerebral ischemic attack. A CT scan revealed massive ascites.
      Laparoscopy showed multiple whitish nodules on the visceral peritoneum and the
      omentum. Peritoneal biopsy revealed tumor cells consistent with malignant
      peritoneal mesothelioma (MPeM). Pemetrexed in combination with cisplatin was
      administered because it has been reported to be active in patients with MPeM.
      However his disease progressed. As second-line therapy paclitaxel was tried which
      yielded a complete response (CR). Eighteen months later he developed abdominal
      pain of the right upper region where a CT scan showed a mass with surrounding
      inflammation. As third-line therapy, gemcitabine was administered and again
      resulted in a CR. He is alive at 3 years from first presenting. Searches for case
      studies published in medical journals on MPeM were carried out, and 59 cases were
      analyzed in comparison with this case.

PMID- 22398912
TI  - Impact of oral iron challenges on circulating non-transferrin-bound iron in
      healthy Guatemalan males.
AB  - INTRODUCTION: Oral iron as a supplement has been associated with adverse health
      consequences, especially in the context of young children with active malaria. A
      potential aggravating role of non-transferrin-bound iron (NTBI) has been
      proposed. MATERIAL AND METHODS: NTBI responses in both a fasting and post-oral
      iron dosing situation were related to serum iron concentration and ferritin
      status. Fasting and 1, 2, and 3 h postdose serum samples were obtained in
      conjunction with oral ferrous sulfate supplementation in aqueous solution of 0,
      15, 30, 60, 120 and 240 mg Fe in a cohort of 8 healthy Guatemalan men over a 9
      week metabolic protocol. Hemoglobin, serum ferritin, percent transferrin
      saturation, serum iron and NTBI were all measured. RESULTS: Circulating levels of
      serum iron and NTBI increased in a graded fashion in response to oral iron, with
      the relative increment for NTBI slightly greater than that of iron. Detectable
      NTBI was occasionally measured in fasting specimens, more frequently in subjects
      with high ferritin status. Post-iron NTBI responses, by contrast, were higher in
      normal-ferritin subjects in absolute terms, and rose with increasing
      postabsorptive serum iron responses. DISCUSSION: The appearance and response of
      circulating NTBI were consistent with recognized principles of iron regulation.

PMID- 22398913
TI  - Detection and kinetic analysis of Epinotia aporema granulovirus in its
      lepidopteran host by real-time PCR.
AB  - Epinotia aporema granulovirus (EpapGV) has attracted interest as a potential
      biocontrol agent of the soybean pest Epinotia aporema in Argentina. Studies on
      virus/host interactions conducted so far have lacked an accurate method to assess
      the progress of virus load during the infection process. The present paper
      reports the development of a real-time PCR for EpapGV and its application to
      describe viral kinetics following ingestion of two different virus doses by last
      instar E. aporema larvae. Real-time PCR was shown to be a reliable method to
      detect and quantify the presence of EpapGV in the analyzed samples. The increase
      in virus titer (log) exhibited a sigmoidal pattern, with an exponential growth
      phase between 24 and 48 h postinfection for both initial doses tested.

PMID- 22398914
TI  - Newcastle disease virus triggers autophagy in U251 glioma cells to enhance virus
      replication.
AB  - Newcastle disease virus (NDV) can replicate in tumor cells and induce apoptosis
      in late stages of infection. However, the interaction between NDV and cells in
      early stages of infection is not well understood. Here, we report that, shortly
      after infection, NDV triggers the formation of autophagosomes in U251 glioma
      cells, as demonstrated by an increased number of double-membrane vesicles, GFP
      microtubule-associated protein 1 light chain 3 (GFP-LC3) a dot formations, and
      elevated production of LC3II. Moreover, modulation of NDV-induced autophagy by
      rapamycin, chloroquine or small interfering RNAs targeting the genes critical for
      autophagosome formation (Atg5 and Beclin-1) affects virus production, indicating
      that autophagy may be utilized by NDV to facilitate its own production.
      Furthermore, the class III phosphatidylinositol 3-kinase (PI3K)/Beclin-1 pathway
      plays a role in NDV-induced autophagy and virus production. Collectively, our
      data provide a unique example of a paramyxovirus that uses autophagy to enhance
      its production.

PMID- 22398915
TI  - Astrovirus in wild boars (Sus scrofa) in Hungary.
AB  - The family Astroviridae consists of two genera, Avastrovirus and Mamastrovirus
      whose members are associated with gastroenteritis in avian and mammalian hosts,
      respectively. In this study, we report the first detection of astrovirus from
      fecal specimens of wild boars (Sus scrofa) using viral metagenomics and complete
      genome sequencing. The wild boar astrovirus (WBAstV-1/2011/HUN, JQ340310) genome
      is 6707 nucleotide long and had 76%, 95% and 56% amino acid (aa) identity in the
      ORF1a (852aa), ORF1b (522aa) and ORF2 (845aa) regions, respectively, to porcine
      astrovirus 4 (PAstV-4, JF713713), the closest match. This study indicates that
      wild boar could be a reservoir for astroviruses.

PMID- 22398916
TI  - Fugu double U6 promoter-driven long double-stranded RNA inhibits proliferation of
      viral hemorrhagic septicemia virus (VHSV) in fish cell lines.
AB  - A long double-stranded RNA (dsRNA)-producing vector driven by fugu double U6
      promotors, in which the two promoters were arranged in a head-to-head fashion,
      was newly constructed. To determine whether the DNA-vector-based long dsRNAs can
      induce sequence-specific RNA interference (RNAi), Epithelioma papulosum cyprini
      (EPC) cells and chinook salmon embryonic (CHSE-214) cells were transfected with
      the long dsRNA vector targeting the G gene of VHSV, and its effect on expression
      of the G gene and viral proliferation was investigated. The sequence-specific
      inhibitory effect was further confirmed by analysis of interferon (IFN)-triggered
      Mx1 gene expression and cross-protection against infectious hematopoietic
      necrosis virus (IHNV). The fugu double U6 promoter-driven vector successfully
      produced long dsRNAs in EPC cells, a system that allows continuous production of
      long dsRNAs in transfected cells. The plasmid-based long dsRNAs targeting the
      VHSV G gene effectively suppressed G gene expression, but control dsRNAs
      targeting the EGFP gene did not. Furthermore, there was no significant difference
      in Mx gene expression between cells transfected with the long dsRNA-producing
      vector and those transfected with the control empty vector. These results suggest
      that G gene expression was suppressed not by type-I-IFN-mediated nonspecific
      inhibition but in a sequence-specific manner. Both EPC and CHSE-214 cells
      transfected with plasmids producing long dsRNAs targeting the VHSV G gene were
      protected against VHSV infection but were not protected against IHNV infection,
      suggesting sequence-specific RNAi-mediated inhibition of viral proliferation. In
      conclusion, we show, for the first time, long-dsRNA-mediated RNAi in fish cells.
      The DNA-vector-based long dsRNAs may provide an efficient tool for analysis of
      gene function in fish cells without preliminary burdensome work for selection of
      effective siRNA clones, and it may be applied as an antiviral measure in cultured
      fish.

PMID- 22398917
TI  - Heterologous expression of viral suppressors of RNA silencing complements
      virulence of the HC-Pro mutant of clover yellow vein virus in pea.
AB  - Many plant viruses encode suppressors of RNA silencing, including the helper
      component-proteinase (HC-Pro) of potyviruses. Our previous studies showed that a
      D-to-Y mutation at amino acid position 193 in HC-Pro (HC-Pro-D193Y) drastically
      attenuated the virulence of clover yellow vein virus (ClYVV) in legume plants.
      Furthermore, RNA-silencing suppression (RSS) activity of HC-Pro-D193Y was
      significantly reduced in Nicotiana benthamiana. Here, we examine the effect of
      expression of heterologous suppressors of RNA silencing, i.e., tomato bushy stunt
      virus p19, cucumber mosaic virus 2b, and their mutants, on the virulence of the
      ClYVV point mutant with D193Y (Cl-D193Y) in pea. P19 and 2b fully and partially
      complemented Cl-D193Y multiplication and virulence, including lethal systemic HR
      in pea, respectively, but the P19 and 2b mutants with defects in their RSS
      activity did not. Our findings strongly suggest that the D193Y mutation
      exclusively affects RSS activity of HC-Pro and that RSS activity is necessary for
      ClYVV multiplication and virulence in pea.

PMID- 22398918
TI  - Effects of different leukocyte subpopulations and flow conditions on leukocyte
      accumulation during reperfusion.
AB  - BACKGROUND/AIMS: The study examined the interdependent effects of shear stress
      and different leukocyte subpopulations on endothelial cell activation and cell
      interactions during low flow and reperfusion. METHODS: Human umbilical venous
      endothelial cells were perfused with either neutrophils or monocytes at different
      shear stress (2-0.25 dyn/cm(2)) and adhesion was quantified by microscopy.
      Effects of adherent neutrophils and monocytes on endothelial cell adhesion
      molecule expression were analyzed by flow cytometry after 4-hour static
      coincubation. After coincubation, the cocultures were reperfused with labeled
      neutrophils at 2 dyn/cm(2) and their adhesion was quantified selectively. For the
      control, endothelium monocultures with and without lipopolysaccharide activation
      were used. RESULTS: At 2 dyn/cm(2), adhesion did not exceed baseline levels on
      nonactivated endothelium. Decreasing shear stress to 0.25 dyn/cm(2) largely
      increased the adhesion of both leukocyte subpopulations, similar to the effect of
      lipopolysaccharide at 2 dyn/cm(2). However, only adherent monocytes increased
      adhesion molecule expression, whereas neutrophils had no effect. As a functional
      consequence, adherent monocytes largely increased neutrophil adhesion during
      reperfusion, whereas adherent neutrophils did not. CONCLUSION: Compromised shear
      stress is an autonomous trigger of leukocyte adhesion even in the absence of
      additional activators. Exceeding this immediate effect, adherent monocytes induce
      further endothelial activation and enhance further neutrophil adhesion during
      reperfusion.

PMID- 22398919
TI  - Making better doctors - using mind-body medicine skills as a self-care element in
      medical education at the Charite University Medical School.

PMID- 22398920
TI  - Knowledge and attitudes of primary health care physicians towards complementary
      and alternative medicine in the Riyadh region, Saudi Arabia.
AB  - BACKGROUND: The aim of this study was to assess the level of knowledge,
      attitudes, and utilization of complementary and alternative medicine (CAM) of
      primary health care (PHC) physicians in Riyadh, Saudi Arabia. MATERIAL AND
      METHODS: A crosssectional study including all physicians working at PHC centers
      in the Riyadh region, Saudi Arabia, was carried out from the beginning of April
      2010 to the end of June 2010. Using a self-administered questionnaire, 1,113
      physicians answered questions regarding their socio-demographic data, and
      knowledge, attitudes and utilization of CAM. RESULTS: About 8% of the
      participants had attended a continuous medical education or a training activity.
      Most of them were unfamiliar with reflexology, energy healing, aromatherapy,
      ozone therapy, homeopathy, or chiropractic care (77.4, 71.3, 71.2, 67.2, 65.7,
      and 63.9%, respectively). On the other hand, most physicians felt that they could
      understand and feel comfortable about counseling patients about Ruqyah (spiritual
      healing), honey and bee products, dietary supplements, massage therapy,
      relaxation, herbal medicine, and cupping (40.3, 38.3, 34.9, 34.4, 25.8, 22.8, and
      21.4%, respectively). More than half (51.7%) of the physicians used CAM for
      themselves or their family, but only 14.2% referred their patients to CAM
      practitioners. 85.1% of studied physicians agreed that physicians should have
      knowledge about CAM therapies commonly used in the region. 82.5% agreed that
      health authorities should have a role in regulating CAM, and 75.7% agreed that
      the physicians' knowledge about CAM practices leads to better patient outcome.
      CONCLUSION: There is a positive attitude regarding the concept of CAM, but there
      is a reluctance to refer or to initiate discussion with patients regarding CAM
      practices, which may be attributed to a lack of knowledge.

PMID- 22398921
TI  - Is it possible to distinguish homeopathic aggravation from adverse effects? A
      qualitative study.
AB  - BACKGROUND: Homeopathic aggravation is a temporary worsening of existing symptoms
      following the administration of a correct homeopathic prescription. The aim of
      this study was to explore and compose criteria that may differentiate homeopathic
      aggravations from adverse effects. MATERIAL AND METHODS: A qualitative approach
      was employed using focus group interviews. 2 interviews, with 11 experienced
      homeopaths, were performed in Oslo, Norway. The practitioners have practiced
      classical homeopathy over a period of 10-32 years. Qualitative content analysis
      was used to analyze the text data. The codes were defined before and during the
      data analysis. RESULTS: We found that aggravations were subtle and multifaceted
      events. Moreover, highly skilled homeopaths are required to identify and report
      aggravations. Adverse effect may be defined as an 'undesirable effect of a
      remedy'. This definition is pragmatic, flexible, and more in line with the
      holistic paradigm that the homeopaths represent. 8 criteria that distinguish
      aggravation from adverse effect were found. Highly sensitive persons hold a
      unique position regarding safety, as it is important to identify these patients
      in order to treat them correctly and avoid undesirable effects of the treatment.
      CONCLUSION: This study rigorously explored homeopaths' views and experience on
      aggravation and adverse effects. The 8 criteria developed in this study may
      ensure patient safety and support therapists in identifying an 'undesirable
      effect of a remedy'.

PMID- 22398922
TI  - Formulation and characterization of a cream containing terminalia chebula
      extract.
AB  - BACKGROUND: This study aimed to formulate a water-in-oil emulsion (formulation)
      of Terminalia chebula versus its vehicle (base) as control, and investigate its
      effects on skin melanin, skin erythema, skin moisture content, and transepidermal
      water loss (TEWL). MATERIAL AND METHODS: Base containing no active material, and
      formulation containing 5% concentrated extract of T. chebula, were developed.
      Different stability parameters were monitored at 8, 25, and 40  degrees C, as
      well as 40  degrees C + 75% relative humidity, for a period of 4 weeks. It was
      concluded that the creams remained stable at all storage conditions. Both base
      and formulation were applied to the cheeks of human volunteers for a period of 8
      weeks. Different skin parameters were monitored every week to measure any effect
      produced by these creams. RESULTS: Changes in TEWL produced by base and
      formulation were insignificant (p > 0.05) with respect to time while significant
      (p <= 0.05) with respect to base and formulation. The skin moisture content
      increased after the application of formulation throughout the study period; this
      effect was insignificant (p > 0.05) with respect to time while significant (p <=
      0.05) with respect to base and formulation. Both base and formulation showed
      insignificant (p > 0.05) effects on skin melanin content with respect to time.
      Skin erythema was reduced by the formulation. Both base and formulation produced
      statistically insignificant (p > 0.05) effects on skin sebum. CONCLUSION: Both
      creams were aesthetic with respect to sensory evaluation. T. chebula topical
      cream showed a positive rejuvenating effect on human skin. Hopefully, this study
      will encourage more attention towards the research and utilization of herbal
      medicines.

PMID- 22398923
TI  - Treatment of venous ulcers with the herbal-based ointment Herbadermal(r): a
      prospective non-randomized pilot study.
AB  - BACKGROUND: Venous ulcers (ulcus cruris venosum) are a common chronic disease
      that requires continuing treatment and significantly influences a patient's way
      of life. The therapeutic effects of the ointment Herbadermal on epithelialization
      and microbial flora of venous ulcers in 25 patients (10 men and 15 women) were
      tested over a 7-week period. The major components of the ointment are extracts of
      garlic, St. John's wort, and calendula. MATERIAL AND METHODS: The patients were
      over 18 years of age, with ulceration of the lower leg no longer than 2 months or
      recurrent ulceration during the last 6 months. The involved patients did not use
      any other phytomedicines or supportive therapies. Parameters were evaluated
      before the treatment and every 2 weeks during the period of 7 weeks. The total
      treatment response was evaluated on the basis of epithelialization, granulation,
      fibrin deposits, exudation, and edema. RESULTS: The percentage of
      epithelialization was 99.1% after 7 weeks, without significant effects on the
      microbial flora. CONCLUSION: This combination of extracts can be recommended as
      topical treatment for wound healing because of its epithelizing, anti
      erythematous, and anti-edematous properties.

PMID- 22398924
TI  - Acupuncture point localization varies among acupuncturists.
AB  - BACKGROUND: Studies assessing the point-specific effect of acupuncture or the
      characteristics of acupuncture points (APs) tend to yield inconclusive results.
      In order to identify a possible confounding factor, we aimed to examine the
      variability in AP localization by means of a survey. MATERIAL AND METHODS:
      Attendees of the 14th ICMART (International Council of Medical Acupuncture and
      Related Techniques) congress as well as DAGfA (German Medical Society of
      Acupuncture) lecturers and students were asked to locate and mark the APs LI 10
      and TH 5 on a research assistant's arm. Identified points were transferred into a
      coordinate system, and the respective bivariate distribution function was
      calculated. Additionally, participants filled out a questionnaire about their
      acupuncture education and experience, the acupuncture style and point
      localization techniques used most frequently, and their estimation of the size of
      an AP. RESULTS: The areas of the ellipses, theoretically containing 95% of AP
      localizations, varied between 44.49 and 5.18 cm(2). The largest distance between
      2 identified points was 8.45 cm for LI 10 and 5.3 cm for TH 5. Apart from being
      trained at the same school, no other factor could be identified that determined
      the variability in AP localization. CONCLUSION: Our results indicate that
      congruity of AP localization among experienced acupuncturists might be low.
      Although there are some limitations to our results, this possible bias should be
      taken into account when conducting acupuncture trials and interpreting results of
      previous acupuncture studies.

PMID- 22398925
TI  - [Demand for and clinical practice of complementary selenium therapy in prostate
      cancer patients].
AB  - BACKGROUND: Selenium supplementation is a popular and broadly adopted
      complementary oncological treatment option. The aim of the study was the
      evaluation of the necessity and the indication for selenium therapy in prostate
      cancer patients. METHODS: 295 consecutive patients after radical prostatectomy
      were evaluated for oncological, basic laboratory and lifestyle characteristics.
      The selenium level was measured using graphite furnace atom absorption
      spectroscopy. RESULTS: The median selenium level was 103.4 (72.9-142.1) MUg/l.
      Correlations were found between a low selenium level and progressed cancer
      disease, positive lymph node status, chronic nicotine and alcohol abuse, and
      chronic multiple medications. CONCLUSION: Based on a documented low selenium
      level in 96.3% of investigated prostate cancer patients and the known
      consequences of an insufficient selenium supply, a targeted selenium
      supplementation is recommended. Selenium therapy should be part of an individual
      medical nutritional and lifestyle intervention.

PMID- 22398928
TI  - Indigenous hydrocarbon-utilizing bacterioflora in oil-polluted habitats in
      Kuwait, two decades after the greatest man-made oil spill.
AB  - Kuwaiti habitats with two-decade history of oil pollution were surveyed for their
      inhabitant oil-utilizing bacterioflora. Seawater samples from six sites along the
      Kuwaiti coasts of the Arabian Gulf and desert soil samples collected from seven
      sites all over the country harbored oil-utilizing bacteria whose numbers made up
      0.0001-0.01% of the total, direct, microscopic counts. The indigenous
      bacterioflora in various sites were affiliated to many species. This was true
      when counting was made on nitrogen-containing and nitrogen-free media. Seawater
      samples harbored species belonging predominantly to the Gammaproteobacteria and
      desert soil samples contained predominantly Actinobacteria. Bacterial species
      that grew on the nitrogen-free medium and that represented a considerable
      proportion of the total in all individual bacterial consortia were diazotrophic.
      They gave positive acetylene-reduction test and possessed the nifH genes in their
      genomes. Individual representative species could utilize a wide range of
      aliphatic and aromatic hydrocarbons, as sole sources of carbon and energy.
      Quantitative determination showed that the individual species consumed crude oil,
      n-octadecane and phenanthrene, in batch cultures. It was concluded that the
      indigenous microflora could be involved in bioremediation programs without
      bioaugmentation or nitrogen fertilization. Irrigation would be the most important
      practice in bioremediation of the polluted soil desert areas.

PMID- 22398929
TI  - Secretome analysis of Clostridium difficile strains.
AB  - Clostridium difficile causes infections ranging from mild C. difficile-associated
      diarrhea to severe pseudomembranous colitis. Since 2003 new hypervirulent C.
      difficile strains (PCR ribotype 027) emerged characterized by a dramatically
      increased mortality. The secretomes of the three C. difficile strains CDR20291,
      CD196, and CD630 were analyzed and compared. Proteins were separated and analyzed
      by means of SDS--PAGE and LC-MS. MS data were analyzed using Mascot and proteins
      were checked for export signals with SecretomeP and SignalP. LC-MS analysis
      revealed 158 different proteins in the supernatant of C. difficile. Most of the
      identified proteins originate from the cytoplasm. Thirty-two proteins in
      CDR20291, 36 in CD196 and 26 in CD630 were identified to be secreted by C.
      difficile strains. Those were mainly S-layer proteins, substrate-binding proteins
      of ABC-transporters, cell wall hydrolases, pilin and unknown hypothetical
      proteins. Toxin A and toxin B were identified after growth in brain heart
      infusion medium using immunological techniques. The ADP-ribosyltransferase
      binding component protein, which is a part of the binary toxin CDT, was only
      identified in the hypervirulent ribotype 027 strains. Further proteins that are
      secreted specifically by hypervirulent strains were identified.

PMID- 22398930
TI  - Covalent immobilization of Kluyveromyces fragilis beta-galactosidase on magnetic
      nanosized epoxy support for synthesis of galacto-oligosaccharide.
AB  - The novel magnetic nanobeads with epoxy groups on the surface were prepared from
      glycidyl methacrylate (GMA), ethylene glycol dimethacrylate (EGDMA) and
      hydroxyethyl methacrylate (HEMA) via emulsifier-free emulsion polymerisation, and
      they were characterized by scanning electron microscopy and vibrating sample
      magnetometer. The magnetic poly(GMA-EDGMA-HEMA) nanobeads were used as support
      for covalent immobilization of Kluyveromyces fragilis beta-galactosidase, the
      maximum amount enzyme attached onto the support was 145.6 mg/g with activity
      recovery of 72.6%. The loading capacity of this novel support for K. fragilis
      beta-galactosidase was improved 2.6-folds compared with Eupergit(r) C (commercial
      epoxy support). The immobilized K. fragilis beta-galactosidase exhibited high
      catalytic activity for the reaction of galacto-oligosaccharide (GOS) synthesis,
      and a total of 2,240 g GOS were produced per gram of immobilized enzyme during
      consecutive batch reaction of 10 times. The immobilized biocatalyst retained
      81.5% of its original activity after 10 reaction cycles.

PMID- 22398931
TI  - Three-dimensional patient setup errors at different treatment sites measured by
      the Tomotherapy megavoltage CT.
AB  - BACKGROUND AND PURPOSE: Reduction of interfraction setup uncertainty is vital for
      assuring the accuracy of conformal radiotherapy. We report a systematic study of
      setup error to assess patients' three-dimensional (3D) localization at various
      treatment sites. PATIENTS AND METHODS: Tomotherapy megavoltage CT (MVCT) images
      were scanned daily in 259 patients from 2005-2008. We analyzed 6,465 MVCT images
      to measure setup error for head and neck (H&N), chest/thorax, abdomen, prostate,
      legs, and total marrow irradiation (TMI). Statistical comparisons of the absolute
      displacements across sites and time were performed in rotation (R), lateral (x),
      craniocaudal (y), and vertical (z) directions. RESULTS: The global systematic
      errors were measured to be less than 3 mm in each direction with increasing order
      of errors for different sites: H&N, prostate, chest, pelvis, spine, legs, and
      TMI. The differences in displacements in the x, y, and z directions, and 3D
      average displacement between treatment sites were significant (p < 0.01). Overall
      improvement in patient localization with time (after 3-4 treatment fractions) was
      observed. Large displacement (> 5 mm) was observed in the 75(th) percentile of
      the patient groups for chest, pelvis, legs, and spine in the x and y direction in
      the second week of the treatment. CONCLUSION: MVCT imaging is essential for
      determining 3D setup error and to reduce uncertainty in localization at all
      anatomical locations. Setup error evaluation should be performed daily for all
      treatment regions, preferably for all treatment fractions.

PMID- 22398932
TI  - Single-sex accommodation: a success story.

PMID- 22398933
TI  - The health and psychosocial burden of alcohol abuse.

PMID- 22398935
TI  - Enhanced recovery after surgery: implications for nurses.
AB  - Enhanced recovery after surgery (ERAS) is a programme of evidence-based
      interventions that minimize the body's response to surgical stress. ERAS enables
      patients to be safely discharged from hospital earlier than previously thought
      possible. This article examines three aspects of enhanced recovery: improving
      preoperative counselling, reducing the body's stress response, and reducing pain
      and promoting comfort. The opportunity for nursing research is discussed in the
      context of patient experiences.

PMID- 22398934
TI  - Cardiovascular disease, statins and vitamin D.
AB  - Cardiovascular disease is the number one killer in the UK, causing more than 50
      000 premature deaths per year, at a cost of over L30 billion to the economy
      (British Heart Foundation, 2010). Reducing this burden is a priority of the
      Government and health professionals (Department of Health, 2000). The aim of this
      paper is to inform and update nurses on four aspects. Firstly, to examine a more
      accurate test than cholesterol to predict cardiovascular risk that used C
      reactive protein (CRP), an inflammatory marker, called the Reynold's Risk Score.
      Use of this score reclassified almost half of women, and one-fifth of men, into
      lower or higher risk categories, more accurately compared to conventional tools
      (Ridker et al, 2007; Ridker et al, 2008b). Secondly, to highlight a potential
      change to the indications for statin-therapy; an indication for those who
      ordinarily would not receive a statin: healthy middle-aged adults with normal or
      low cholesterol, but elevated CRP. This includes discussion of the JUPITER trial
      and its sub-analyses. This large, multicentre, double-blind randomized, placebo
      controlled trial in apparently healthy men over the age of 50 years and women
      over 60 years, with normal or low cholesterol but elevated CRP, demonstrated
      significant benefit. Rosuvastatin 20 mg per day compared to a placebo reduced
      myocardial infarction and stroke by half, and reduced venous thromboembolism by
      almost half (Ridker et al, 2008a; Glynn et al. 2009; Everett, et al, 2010).
      Thirdly, to discuss the pleiotropic effects of statins, which include reduction
      of CRP (Ridker et al, 2008a), increases in endothelial repair cells (Spiel, et
      al, 2008), alteration of clotting factors (Glynn, et al, 2009), and enhancement
      of vitamin D metabolism (Yavuz et al, 2009). Fourthly, to discuss evidence that
      the pleiotropic effects of statins may be attributable to the vitamin D effect.
      This paper therefore evaluates the evidence suggesting that vitamin D
      supplementation may attain the same benefit as statins (Grimes, 2006), in
      addition to reducing statinassociated side-effects when co-administered (Ahmed et
      al, 2009).

PMID- 22398936
TI  - Effectiveness of dose adjustment for normal eating (DAFNE).
AB  - This literature review examines the evidence base behind Dose Adjustment for
      Normal Eating (DAFNE), an educational programme for the self-management of type 1
      diabetes. The Cumulative Index to Nursing and Allied Health Literature (CINAHL),
      British Nursing Index (BNI), Embase and Medline databases were accessed to locate
      relevant studies. Twelve studies were found to meet the review criteria. These
      provide evidence that DAFNE can help people with type 1 diabetes to achieve
      better glycaemic control and improve their quality of life. However, DAFNE
      induced improvements in glycaemic control tend to reduce as time elapses since
      programme attendance and literature on the long-term effectiveness is limited.
      More research is needed to determine whether the benefits last in the long term
      and to identify how its positive effects can be maintained.

PMID- 22398937
TI  - The Mental Health Act: exploring the role of nurses.
AB  - This paper examines the role of approved mental health professional (AMHP) which
      was introduced by the Mental Health Act 2007. It outlines the scope and functions
      of the role and explores the likely impact on the nursing profession. While the
      expansion of the role does offer opportunities for career progression and
      enhancing professional autonomy and status, it must be accompanied by a
      corresponding increase in resources and training, to enable nurses to fully
      harness the AMHP role. This expansion will inevitably bring with it increased
      legal responsibility and accountability and the extent to which mental
      health/learning disability nurses will be willing to shoulder that remains to be
      seen.

PMID- 22398938
TI  - Exploring compassion: implications for contemporary nursing. Part 2.
AB  - A range of contemporary political and professional literature endorse the
      principle of compassion in nursing as a core and underpinning philosophy
      fundamental to the profession. However, despite pledges to ensure that compassion
      lies at the heart of nursing, the concept has not been clearly defined. It is
      evident that uncovering the true meaning is complex and challenging owing to its
      subjective nature. In light of this, several implications must be considered.
      Effective student nurse recruitment is essential to ensure that the most
      appropriate individuals are selected. Contemporary marketing campaigns must be
      implemented, and recruitment strategies developed, which consider specific values
      and attitudes. Service user involvement in recruitment and selection, curriculum
      planning and learning and teaching strategies, and post-qualification education,
      can enhance nurses' understanding of the patient perspective and make headway in
      embedding compassion as a core nursing value. Additionally, effective role
      modelling in practice which demonstrates high-quality compassionate nursing care
      is essential. Nurses must be adequately supported in the clinical environment to
      facilitate compassionate behaviours and clinical leadership at all levels must
      uphold political and professional pledges to achieve this. Consideration of these
      implications for practice is essential to ensure that nurses are able to respond
      to patients with humanity and kindness, and deliver high-quality, compassionate
      care to all.

PMID- 22398939
TI  - Pneumonia part 2: signs, symptoms and vaccinations.
AB  - Streptococcus pneumoniae is a cause of significant morbidity and mortality
      worldwide. There are many different serotypes of the organism which may be
      carried by up to 50% of children under the age of 6 years, as well as many
      adults. The organism is associated with both pneumonia and invasive pneumococcal
      disease, which may result in septicemia or meningitis. It is also a principal
      cause of otits media and sinusitis, which are not life-threatening, but generate
      a lot of discomfort, loss of schooling or working days, and around 60 000 GP
      consultations per year in the UK. Vaccination is a safe and effective way to
      prevent this infection from causing significant ill health.

PMID- 22398940
TI  - Assisted suicide: a right to professionally-aided death?
AB  - The article examines the recent decision in the case of Re AM (2012), in which a
      man in a locked in state seeks assistance in dying. The preliminary hearing in
      this case decided in January 2012 concerns whether AM's lawyers can provide
      professional assistance in relation to providing information about assisted
      suicide. The article explores the issue of professional assistance in the suicide
      process; something which is particularly controversial following the recent
      guidelines (The Crown Prosecution Service, 2010) on prosecution in the case of
      assisted suicide.

PMID- 22398941
TI  - Professional development: from staff nurse to nurse consultant. Part 6: master
      and PhD degrees.

PMID- 22398942
TI  - Recovery from cancer through sport and activity.

PMID- 22398943
TI  - Patient safety in the developing world: new frontiers.
AB  - Patient safety is not only a vitally important concept for nurses and doctors in
      the developed world, but is also essential for those in the developing world.
      Consequently, the World Health Organization (WHO) has launched the WHO African
      Partnership for Patient Safety (APPS) project, which brings together nurses,
      doctors and other health professionals in both UK and African hospitals to
      enhance patient safety. This article will discuss the APPS project alongside a
      report (WHO, 2008) from the Regional Director, Regional Office for Africa, which
      outlines key patient safety challenges and opportunities. Some are particularly
      relevant to hospitals in the developed world, whereas others can apply to all
      hospitals.

PMID- 22398944
TI  - Does the care quality commission need to be strengthened?

PMID- 22398945
TI  - How to choose and apply for the perfect job.

PMID- 22398946
TI  - Nursing in the future tense, not the past.

PMID- 22398947
TI  - Synthesis of 1,2-bisalkylidenecyclopentanes from 1,6-allenynes via
      stereoselective addition of nucleophiles to ruthenacyclopentenes.
AB  - Ruthenium-catalyzed cyclization of 1,6-allenynes occurs via the addition of
      heteroatom nucleophiles to ruthenacyclopentenes, providing functionalized 1,2
      bisalkylidenecyclopentanes in a highly regio- and stereoselective manner.

PMID- 22398949
TI  - Improving density functional theory for crystal polymorph energetics.
AB  - We show that the quality of density functional theory (DFT) predictions for the
      relative stabilities of polymorphs of crystalline para-diiodobenzene (PDIB) is
      dramatically improved through a simple two-body correction using wavefunction
      based electronic structure theory. PDIB has two stable polymorphs under ambient
      conditions, and like Hongo et al. [J. Phys. Chem. Lett., 1, 1789 (2010)] we find
      that DFT makes wildly variable predictions of the relative stabilities, depending
      on the approximate functional used. The two-body corrected scheme, using Grimme's
      spin-scaled variant of second-order Moller-Plesset perturbation theory and any of
      the tested density functionals, predicts the alpha-polymorph to be more stable,
      consistent with experiment, and produces a relative stability that agrees with
      the benchmark quantum Monte-Carlo results of Hongo et al. within statistical
      uncertainty.

PMID- 22398948
TI  - Increased risk of unfavorable metabolic outcome during short-term follow-up in
      subjects with nonfunctioning adrenal adenomas.
AB  - OBJECTIVE: To demonstrate long-term changes in the prevalence of several types of
      metabolic derangements in subjects with nonfunctioning adrenal adenomas. SUBJECTS
      AND METHODS: 273 subjects with adrenal adenomas, including 231 with
      nonfunctioning adenoma and 42 with subclinical Cushing's syndrome (sCS), were
      evaluated with respect to anthropometric and laboratory characteristics and
      prevalence of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia,
      metabolic syndrome (MS), prediabetes and cardiovascular disease (CVD). Median
      duration was 24 months. Follow-up data of 114 participants with nonfunctioning
      adrenal adenomas are also presented while those of 117 were missing. Follow-up
      data regarding changes in anthropometric and laboratory parameters and prevalence
      rates of metabolic disturbances were obtained from the medical records. RESULTS:
      The prevalence rates for both patients with nonfunctioning adenoma and sCS were:
      dyslipidemia: 161 (59%), hypertension: 147 (54%), MS: 128 (47%), prediabetes: 62
      (23%), T2DM: 49 (18%), and CVD: 21 (8%). Hypertension and CVD were prevalent in
      subjects with sCS compared to participants with nonfunctioning adenoma. In follow
      up, body mass index (p = 0.005), systolic blood pressure (p < 0.001), waist
      circumference (p = 0.005), homeostasis model assessment (p = 0.046), high
      sensitivity C-reactive protein (p = 0.023), total cholesterol (p < 0.001) and low
      density lipoprotein cholesterol (p < 0.001) and prevalence of hypertension (p <
      0.001), dyslipidemia (p < 0.001), prediabetes (p < 0.001) and MS (p < 0.01)
      significantly increased in subjects with nonfunctioning adenoma. CONCLUSION: The
      data showed that nonfunctioning adrenal adenomas were associated with the
      development or deterioration of atherosclerotic risk factors. Therefore, follow
      up and management strategies should be developed to decrease atherosclerotic
      morbidity in those individuals.

PMID- 22398950
TI  - First human case of co-infection with two different subtypes of hepatitis E
      virus.
AB  - Hepatitis E virus (HEV), the main etiologic agent of enterically transmitted
      acute hepatitis in developing countries, is now recognized as an emerging agent
      of autochthonous disease and chronic hepatitis E in immunocompromised patients in
      Europe where HEV infection is probably zoonotically acquired. We describe the
      first human case of acute HEV infection with two genotype 3 viruses in a French
      kidney transplant recipient, probably acquired through consumption of uncooked
      pig liver sausage (figatellu). The patient presented two viral sequences nearly
      identical to sequences recovered from figatelli. Autochthonous co-infections with
      different genotype 3 HEV strains can occur in our geographical area.

PMID- 22398951
TI  - Effects of plasma kallikrein deficiency on haemostasis and thrombosis in mice:
      murine ortholog of the Fletcher trait.
AB  - Plasma kallikrein is a multifunctional serine protease involved in contact
      activation of coagulation. Deficiency in humans is characterised by prolonged
      activated partial thromboplastin time (aPTT); however, the balance between
      thrombosis and haemostasis is not fully understood. A study of plasma kallikrein
      deficient mice revealed increased aPTT, without prolonged bleeding time.
      Prekallikrein antisense oligonucleotide (ASO) treatment in mice suggested
      potential for a positive therapeutic index. The current goal was to further
      define the role of plasma kallikrein in coagulation. Blood pressure and heart
      rate were normal in plasma kallikrein-deficient mice, and mice were completely
      protected from occlusion (100 +/- 1.3% control flow) in 3.5% FeCl3 -induced
      arterial thrombosis versus heterozygotes (20 +/- 11.4%) and wild-type littermates
      (8 +/- 0%). Vessels occluded in 8/8 wild-type, 7/8 heterozygotes, and 0/8
      knockouts. Anti-thrombotic protection was less pronounced in 5% FeCl3-induced
      arterial injury. Integrated blood flow was 8 +/- 0% control in wild-type and
      heterozygotes, and significantly (p<0.01) improved to 43 +/- 14.2% in knockouts.
      The number of vessels occluded was similar in all genotypes. Thrombus weight was
      significantly reduced in knockouts (-47%) and heterozygotes (-23%) versus wild
      type in oxidative venous thrombosis. Average tail bleeding time increased
      modestly in knockout mice compared to wild-type. Average renal bleeding times
      were similar in all genotypes. These studies confirm and extend studies with
      prekallikrein ASO, and demonstrate that plasma kallikrein deletion prevents
      occlusive thrombus formation in mice with a minimal role in provoked bleeding.
      Additional support for the significance of the intrinsic pathway in the
      coagulation cascade is provided, as well as for a potential new anti-thrombotic
      approach.

PMID- 22398952
TI  - [Bleeding and coagulation disorders in tonsillectomies].
AB  - BACKGROUND: The aim of our prospective analysis was to show the incidence of
      bleeding disorders among a tonsillectomy patient population and in case of
      bleeding disorders. PATIENTS AND METHODS: This study comprised 92 consecutive
      patients who underwent tonsillectomies from 1 January 2007 to 31 December 2007 at
      the Department of Otorhinolaryngology, University Medical Center Mainz. In
      addition to gender, age, date of bleeding, Quick, aPTT and platelet count, the
      following blood values were determined: vWF:AG, vWF:RCo, vWF:RCo/vWF:AG, factor
      XIII, factor VIII:C, PFA 100TM ADP and PFA 100TM epinephrine (special coagulation
      analysis). RESULTS: Twelve of 92 patients (13%) showed evidence of coagulopathy.
      Four of these 12 patients had a postoperative hemorrhage. In eight patients a
      factor XIII deficiency was diagnosed, with two of them suffering a hemorrhage. In
      four patients, von Willebrand disease was diagnosed; two of them bled. No
      correlation between the presence of a coagulopathy and the bleeding rate could be
      determined. CONCLUSION: Routine preoperative performance of special coagulation
      analysis in all patients does not significantly contribute to the detection of
      increased postoperative hemorrhage risk.

PMID- 22398953
TI  - Comparison of monodisperse droplet generation in flow-focusing devices with
      hydrophilic and hydrophobic surfaces.
AB  - A thin flow-focusing microfluidic channel is evaluated for generating
      monodisperse liquid droplets. The microfluidic device is used in its native
      state, which is hydrophilic, or treated with OTS to make it hydrophobic. Having
      both hydrophilic and hydrophobic surfaces allows for creation of both oil-in
      water and water-in-oil emulsions, facilitating a large parameter study of
      viscosity ratios (droplet fluid/continuous fluid) ranging from 0.05 to 96 and
      flow rate ratios (droplet fluid/continuous fluid) ranging from 0.01 to 2 in one
      geometry. The hydrophilic chip provides a partially-wetting surface (contact
      angle less than 90 degrees ) for the inner fluid. This surface, combined with the
      unusually thin channel height, promotes a flow regime where the inner fluid wets
      the top and bottom of the channel in the orifice and a stable jet is formed.
      Through confocal microscopy, this fluid stabilization is shown to be highly
      influenced by the contact angle of the liquids in the channel. Non-wetting jets
      undergo breakup and produce drops when the jet is comparable to or smaller than
      the channel thickness. In contrast, partially-wetting jets undergo breakup only
      when they are much smaller than the channel thickness. Drop sizes are found to
      scale with a modified capillary number based on the total flow rate regardless of
      wetting behavior.

PMID- 22398954
TI  - Psychoacoustic performance and music and speech perception in prelingually
      deafened children with cochlear implants.
AB  - The number of pediatric cochlear implant (CI) recipients has increased
      substantially over the past 10 years, and it has become more important to
      understand the underlying mechanisms of the variable outcomes in this population.
      In this study, psychoacoustic measures of spectral-ripple and Schroeder-phase
      discrimination, the Clinical Assessment of Music Perception, and consonant
      nucleus-consonant (CNC) word recognition in quiet and spondee reception threshold
      (SRT) in noise tests have been presented to 11 prelingually deafened CI users,
      aged 8-16 years with at least 5 years of CI experience. The children's
      performance was compared to the previously reported results of postlingually
      deafened adult CI users. The average spectral-ripple threshold (n = 10) was 2.08
      ripples/octave. The average Schroeder-phase discrimination was 67.3% for 50 Hz
      and 56.5% for 200 Hz (n = 9). The Clinical Assessment of Music Perception test
      showed that the average complex pitch direction discrimination was 2.98
      semitones. The mean melody score was at a chance level, and the mean timbre score
      was 34.1% correct. The mean CNC word recognition score was 68.6%, and the mean
      SRT in steady noise was -8.5 dB SNR. The children's spectral-ripple resolution,
      CNC word recognition, and SRT in noise performances were, within statistical
      bounds, the same as in a population of postlingually deafened adult CI users.
      However, Schroeder-phase discrimination and music perception were generally
      poorer than in the adults. It is possible then that this poorer performance seen
      in the children might be partly accounted for by the delayed maturation in their
      temporal processing ability, and because of this, the children's performance may
      have been driven more by their spectral sensitivity.

PMID- 22398955
TI  - A sparse transmission disequilibrium test for haplotypes based on Bradley-Terry
      graphs.
AB  - BACKGROUND: Linkage and association analysis based on haplotype transmission
      disequilibrium can be more informative than single marker analysis. Several works
      have been proposed in recent years to extend the transmission disequilibrium test
      (TDT) to haplotypes. Among them, a powerful approach called the evolutionary tree
      TDT (ET-TDT) incorporates information about the evolutionary relationship among
      haplotypes using the cladogram of the locus. METHODS: In this work we extend this
      approach by taking into consideration the sparsity of causal mutations in the
      evolutionary history. We first introduce the notion of a Bradley-Terry (BT) graph
      representation of a haplotype locus. The most important property of the BT graph
      is that sparsity of the edge set of the graph corresponds to small number of
      causal mutations in the evolution of the haplotypes. We then propose a method to
      test the null hypothesis of no linkage and association against sparse
      alternatives under which a small number of edges on the BT graph have non-nil
      effects. RESULTS AND CONCLUSION: We compare the performance of our approach to
      that of the ET-TDT through a power study, and show that incorporating sparsity of
      causal mutations can significantly improve the power of a haplotype-based TDT.

PMID- 22398956
TI  - In vivo experimental imaging of osteochondral defects and their healing using
      (99m)Tc-NTP 15-5 radiotracer.
AB  - PURPOSE: A rabbit model of osteochondral defects (OD) and spontaneous healing was
      longitudinally followed over 12 weeks, by in vivo joint scintigraphy using
      (99m)Tc-NTP 15-5, and histology. METHODS: We used two models, one with one OD
      (OD1 group) in the femoral condyle of one knee and the other with two ODs (OD2
      group) in the femoral condyle of one knee, with the contralateral knees serving
      as the reference. A serial longitudinal imaging study was performed with the
      scintigraphic ratio (SR, operated knee uptake/contralateral knee uptake)
      determined at each time-point. RESULTS: ODs were imaged as radioactive defects.
      The SR was decreased with respective to controls, with values of 0.73 +/- 0.08
      and 0.65 +/- 0.07 in the OD1 and OD2 groups, respectively, at 4 weeks after
      surgery. Histology of both OD groups revealed the presence of repair tissue
      characterized by a small amount of sulphated glycosaminoglycans and collagen.
      CONCLUSION: (99m)Tc-NTP 15-5 imaging provided quantitative criteria useful for in
      vivo evaluation of cartilage trauma and healing.

PMID- 22398957
TI  - Quantification of myocardial blood flow with 82Rb positron emission tomography:
      clinical validation with 15O-water.
AB  - PURPOSE: Quantification of myocardial blood flow (MBF) with generator-produced
      (82)Rb is an attractive alternative for centres without an on-site cyclotron. Our
      aim was to validate (82)Rb-measured MBF in relation to that measured using (15)O
      water, as a tracer 100% of which can be extracted from the circulation even at
      high flow rates, in healthy control subject and patients with mild coronary
      artery disease (CAD). METHODS: MBF was measured at rest and during adenosine
      induced hyperaemia with (82)Rb and (15)O-water PET in 33 participants (22 control
      subjects, aged 30 +/- 13 years; 11 CAD patients without transmural infarction,
      aged 60 +/- 13 years). A one-tissue compartment (82)Rb model with ventricular
      spillover correction was used. The (82)Rb flow-dependent extraction rate was
      derived from (15)O-water measurements in a subset of 11 control subjects.
      Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson's
      correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin's concordance
      correlation rho (c) (measuring both precision and accuracy) were used. RESULTS:
      Over the entire MBF range (0.66-4.7 ml/min/g), concordance was excellent for MBF
      (r = 0.90, [(82)Rb-(15)O-water] mean difference +/- SD = 0.04 +/- 0.66 ml/min/g,
      LoA = -1.26 to 1.33 ml/min/g, rho(c) = 0.88) and MFR (range 1.79-5.81, r = 0.83,
      mean difference = 0.14 +/- 0.58, LoA = -0.99 to 1.28, rho(c) = 0.82). Hyperaemic
      MBF was reduced in CAD patients compared with the subset of 11 control subjects
      (2.53 +/- 0.74 vs. 3.62 +/- 0.68 ml/min/g, p = 0.002, for (15)O-water; 2.53 +/-
      1.01 vs. 3.82 +/- 1.21 ml/min/g, p = 0.013, for (82)Rb) and this was paralleled
      by a lower MFR (2.65 +/- 0.62 vs. 3.79 +/- 0.98, p = 0.004, for (15)O-water; 2.85
      +/- 0.91 vs. 3.88 +/- 0.91, p = 0.012, for (82)Rb). Myocardial perfusion was
      homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in
      MBF among the coronary artery territories (p > 0.31). CONCLUSION: Quantification
      of MBF with (82)Rb with a newly derived correction for the nonlinear extraction
      function was validated against MBF measured using (15)O-water in control subjects
      and patients with mild CAD, where it was found to be accurate at high flow rates.
      (82)Rb-derived MBF estimates seem robust for clinical research, advancing a step
      further towards its implementation in clinical routine.

PMID- 22398958
TI  - Comparison of 11C-PiB and 18F-florbetaben for Abeta imaging in ageing and
      Alzheimer's disease.
AB  - PURPOSE: Amyloid imaging with (18)F-labelled radiotracers will allow widespread
      use of this technique, facilitating research, diagnosis and therapeutic
      development for Alzheimer's disease (AD). The purpose of this analysis was to
      compare data on cortical Abeta deposition in subjects who had undergone both
      (11)C-PiB (PiB) and (18)F-florbetaben (FBB) PET imaging. METHODS: We identified
      ten healthy elderly controls (HC) and ten patients with AD who had undergone PET
      imaging after intravenous injection of 370 MBq of PiB and 300 MBq of FBB under
      separate research protocols. PiB and FBB images were coregistered so that
      placement of regions of interest was identical on both scans and standard uptake
      value ratios (SUVR) using the cerebellar cortex as reference region were
      calculated between 40 and 70 min and between 90 and 110 min after injection for
      PiB and FBB, respectively. RESULTS: Significantly higher SUVR values (p < 0.0001)
      in most cortical areas were observed in AD patients when compared with HC with
      both radiotracers. Global SUVR values in AD patients were on average 75% higher
      than in HC with PiB and 56% higher with FBB. There was an excellent linear
      correlation between PiB and FBB global SUVR values (r = 0.97, p < 0.0001) with
      similar effect sizes for distinguishing AD from HC subjects for both radiotracers
      (Cohen's d 3.3 for PiB and 3.0 for FBB). CONCLUSION: FBB, while having a narrower
      dynamic range than PiB, clearly distinguished HC from AD patients, with a
      comparable effect size. FBB seems a suitable (18)F radiotracer for imaging AD
      pathology in vivo.

PMID- 22398959
TI  - Effects of adipose-derived mesenchymal cells on ischemia-reperfusion injury in
      kidney.
AB  - BACKGROUND: Acute kidney injury (AKI) is a critical condition for kidney and
      other remote organs, including the lung. However, available treatments for AKI
      are limited. In this study, we explored the effect of adipose-derived mesenchymal
      cells on a mouse model of AKI. METHODS: Adipose-derived mesenchymal cells were
      isolated from mouse subcutaneous and peritoneal adipose tissue by digestion with
      collagenase type I. The left renal artery and vein of C57BL/6 mice were clamped
      for 45 min to induce ischemia and were injected with the adipose-derived
      mesenchymal cells [1 * 10(5) cells/0.2 ml phosphate-buffered saline (PBS)] or 0.2
      ml PBS via the tail vein on days 0, 1, and 2. RESULTS: The adipose-derived
      mesenchymal cells had stem-cell surface markers and multilineage differentiating
      potentials. Administered adipose-derived mesenchymal cells homed primarily into
      lung. Interestingly, repeated administration of adipose-derived mesenchymal cells
      reduced acute tubular necrosis and interstitial macrophage infiltration in the
      injured kidney, accompanied with reduced cytokine and chemokine expression.
      CONCLUSION: Adipose-derived mesenchymal cells can be used as cell-based therapy
      for ischemic kidney injury.

PMID- 22398960
TI  - Endoscopic pyloric balloon dilatation obviates the need for pyloroplasty at
      esophagectomy.
AB  - BACKGROUND: Because the rate of acquired pyloric stenosis (APS) from truncal
      vagotomy is 15%, many surgeons perform pyloroplasty or pyloromyotomy at the time
      of esophagectomy. Endoscopic pyloric balloon dilatation (EPBD) is another method
      to manage APS. This study evaluated a cohort treated with preoperative EPBD.
      METHODS: This is a retrospective review of all patients treated with preoperative
      EPBD and esophagectomy for cancer from 2002 to 2009 at Brigham and Women's
      Hospital, a tertiary care center. Outcome measures included need for subsequent
      surgery for gastric outlet obstruction, rate of pyloric stenosis noted on
      postoperative endoscopy, and complications. RESULTS: Upon review of the series,
      25 patients (80% male; median age, 63 [range 47-81] years) had outpatient
      preoperative EPBD and esophagectomies 1-2 weeks later and were included in the
      study. None had pyloroplasties or pyloromyotomies at the time of esophagectomy.
      Selected patients had postoperative endoscopy. Of the 25 patients, 20 had
      transhiatal esophagectomies, 3 had thoracoabdominal esophagectomies, and 2 had
      VATS 3-hole esophagectomies. Median follow-up time was 22 (range, 1-84) months.
      There were no complications from EPBD. There were no postoperative deaths. No
      patient needed a second operation for gastric outlet obstruction. All patients
      had postoperative barium swallows (BaS) or endoscopy or both. Only one patient
      (4%) required one postoperative EPBD to dilate a 16-mm pylorus. Three others had
      delayed gastric emptying on BaS with endoscopy showing each pylorus was wide
      open. Their symptoms improved with time. CONCLUSIONS: In this cohort,
      preoperative EPBD in all patients combined with postoperative EPBD in one patient
      obviated the need for pyloroplasty. This approach merits further study in a
      larger cohort, particularly to determine whether preoperative EPBD is necessary
      or if only selected postoperative EPBD is sufficient.

PMID- 22398961
TI  - Outcome of laparoscopic cholecystectomy conversion: is the surgeon's selection
      needed?
AB  - BACKGROUND: Risk factors for conversion in cholecystectomy may be of clinical
      value. This study aimed to investigate whether a set of risk factors, including
      the surgeon's specialization, can be used for the development of a preoperative
      strategy to optimize conversion outcome. METHODS: The data for all patients who
      underwent laparoscopic cholecystectomy at a single institution between January
      2004 and December 2008 were retrospectively reviewed. Factors predictive for
      conversion were identified, and a preoperative strategy model was deduced.
      RESULTS: Of the 1,126 patients analyzed, 106 (9%) underwent laparoscopic
      cholecystectomy in an emergency setting. Delayed surgery was performed for 63
      (46%) of 138 patients (12%) with acute cholecystitis. Preoperative endoscopic
      retrograde cholangiography was achieved for 161 of the patients (14%). Risk
      factors predictive of conversion (for 65 patients) were male gender [odds ratio
      (OR), 2.3; 95% confidence interval (CI), 1.3-3.9; p = 0.004], age older than 65
      years (OR, 2.6; 95% CI, 1.4-4.8; p = 0.002), body mass index (BMI) exceeding 25
      kg/m(2) (OR, 3.4; 95% CI, 1.7-7.1; p < 0.001), history of complicated biliary
      disease (HCBD) (OR, 5.6; 95% CI, 3.2-9.8; p = < 0.001), and surgery by a non
      gastrointestinal (non-GI) surgeon (OR, 4.9; 95% CI, 2.2-10.6; p < 0.001). The
      conversion rate for patients with a history of no complications who had two or
      more risk factors (gender, age, BMI > 25) and for patients with a HCBD who had
      one or more risk factors was significantly higher if the surgery was performed by
      non-GI rather than GI surgeons. CONCLUSION: Male gender, age older than 65 years,
      BMI exceeding 25 kg/m(2), HCBD, and surgery by a non-GI surgeon are predictive
      for conversion. A preoperative triage for surgeon selection based on risk factors
      and a HCBD is proposed to optimize conversion outcome.

PMID- 22398962
TI  - Risk factors for perforations associated with endoscopic submucosal dissection in
      gastric lesions: emphasis on perforation type.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) enables en bloc resection of
      larger gastric neoplasms. However, the procedure is associated with a high
      incidence of perforation. Perforations during ESD are divided into macro- and
      microperforations. Although both types of perforations could cause widespread
      tissue injury and secondary sepsis, very little is known concerning the risk
      factors for perforations according to the type of perforation. Thus, this study
      was performed to evaluate the risk factors for macro-, micro-, and all
      perforations (both) during ESD. METHODS: 823 gastric lesions (gastric adenoma or
      early gastric cancer) in 729 patients treated by ESD were enrolled, and their
      records were reviewed retrospectively. Risk factors were evaluated, focusing on
      age, sex, gastric neoplasm-related factors (12 locations, resected size, gross
      type of lesions, presence of ulceration, presence of fibrosis, pathologic
      diagnosis, and depth of invasion), and ESD procedure-related factors (type of
      knife, immediate bleeding during ESD, en bloc resection, procedure time, and the
      number of ESD cases experienced by the endoscopist). RESULTS: Of the 823 gastric
      lesions, the rates of all perforation, macroperforation, and microperforation
      were 9.6%, 7.5%, and 2.1%, respectively. Risk factors for all perforations on
      multivariate analysis were location of tumor in upper portion, presence of
      fibrosis, and long procedure time (>2 h). Risk factors for macroperforations were
      the same as all perforations. Risk factors for microperforations on multivariate
      analysis were old age (>=81 years), depth of invasion (muscularis mucosa), and
      long procedure time (>2 h). CONCLUSIONS: The risk factors for perforations during
      ESD could differ according to the type of perforation. Therefore, although
      macroperforation did not develop during ESD, it would be necessary to consider
      the possibility of microperforation in case of old age, long procedure time, and
      (deep) depth of invasion.

PMID- 22398964
TI  - Dosing rationale for fixed-dose combinations in children: shooting from the hip?
AB  - In this investigation we evaluate the relevance of a model-based approach for
      pharmacokinetic (PK) bridging and dose selection of drug combinations in
      children. The fixed-dose combination of atovaquone (ATV) and proguanil (PGN) was
      used for illustration purposes. A population PK model was developed for each
      compound using plasma concentration data from adult and pediatric patients. PK
      parameter estimates were subsequently used to simulate drug exposure in children
      treated with different dose levels of these drugs. We show that, contrary to
      common practice, different dose ratios may be required across age groups in order
      to achieve target exposure levels comparable to adults. This example illustrates
      the effects of covariate interactions, specifically the ones involving body
      weight (BW) and ethnicity, on the PK of drugs. A model-based approach is critical
      for dose selection and the rational use of drug combinations in children.
      Flexible rather than fixed-dose ratios may be needed to ensure comparable target
      exposure in bridging studies.

PMID- 22398963
TI  - Outcomes of acute phase cognitive therapy in outpatients with anxious versus
      nonanxious depression.
AB  - OBJECTIVE: Compared to nonanxious depressed patients, anxious depressed patients
      respond less to pharmacotherapy, prompting consideration of alternate treatments.
      Based on the transdiagnostic principles of cognitive therapy (CT), we predicted
      that anxious depressed patients would respond as well to CT as nonanxious
      depressed patients. METHOD: Adults (n = 523) with recurrent major depressive
      disorder received 12-14 weeks of CT as part of the Continuation Phase Cognitive
      Therapy Relapse Prevention Trial. Anxious depressed patients (n = 264; 50.4%)
      were compared to nonanxious depressed patients (n = 259; 49.6%) on demographic
      variables, initial severity, attrition, and rates and patterns of response and
      remission. RESULTS: Anxious depressed patients presented with greater illness
      severity and had significantly lower response (55.3 vs. 68.3%) and remission
      rates (26.9 vs. 40.2%) based on clinician-administered measures. By contrast,
      smaller between-group differences for attrition, and for response (59.1 vs.
      64.9%) and remission (41.7 vs. 48.7%) rates on self-report measures were not
      significant. Further, anxious depressed patients had greater speed of improvement
      on self-reported anxiety symptom severity and clinician-rated depressive and
      anxiety symptom severity measures. CONCLUSION: Consistent with prior reports,
      anxious depressed patients presented with greater severity and, following CT, had
      lower response and remission rates on clinician-administered scales. However,
      anxious depressed patients improved more rapidly and response and remission rates
      on self-report measures were not significantly different from nonanxious
      depressed patients. Our findings suggest that anxious depressed patients may
      simply need additional time or more CT sessions to reach outcomes fully
      comparable to those of less anxious patients.

PMID- 22398965
TI  - Regulatory aspects of new medicines targeted at treatment of autoimmune diseases.
AB  - Autoimmune diseases comprise a diverse group of clinical dis orders that result
      from the body's adaptive immune system reacting against its own tissues.(1)
      Conversely, autoinflammatory disorders encompass a more limited group of diseases
      distinguished by recurrent episodes of inflammation but in the absence of high
      titer autoantibodies and antigen-specific T cells.(2) The past 15 years have seen
      a tremendous growth in the development of highly effective treatments for these
      diseases.

PMID- 22398966
TI  - Predicting drug interaction potential with a physiologically based
      pharmacokinetic model: a case study of telithromycin, a time-dependent CYP3A
      inhibitor.
AB  - Telithromycin is a substrate and an inhibitor of cytochrome P450 3A (CYP3A4),
      with dose- and time-dependent nonlinear pharmacokinetics (PK). We hypothesized
      that the time-dependent inhibition (TDI) of CYP3A4 was responsible for the
      nonlinear PK of telithromycin and then used physiologically based PK (PBPK)
      modeling and simulation to verify this mechanism. Telithromycin PBPK models
      integrating in vitro, in silico, and in vivo PK data ruled out the contribution
      of enzyme/transporter saturation and suggested that TDI is a plausible mechanism
      for PK nonlinearity. The model successfully predicted the clinical interaction
      with the CYP3A4 substrate midazolam, as verified by external data not used for
      the model-building (intravenous (i.v.) and oral (p.o.) midazolam area under the
      concentration-time curve (AUC) ratio with/without concurrent telithromycin
      administration: 3.26 and 6.72 predicted vs. 2.20 and 6.11 observed,
      respectively). Models assuming reversible inhibition failed to predict such
      strong CYP3A4 inhibition. In the absence of in vitro TDI data, a PBPK model can
      be used to incorporate TDI mechanisms based on nonlinear PK data to predict
      clinical drug-drug interactions.

PMID- 22398967
TI  - Warfarin-amiodarone drug-drug interactions: determination of [I](u)/K(I,u) for
      amiodarone and its plasma metabolites.
AB  - A retrospective clinical evaluation in a cohort of 73 patients receiving stable
      anticoagulation therapy showed that the addition/elimination of amiodarone
      resulted in a 6-65% change in warfarin dose requirement. To evaluate the roles of
      amiodarone and its circulating metabolites in this highly variable inhibitory
      drug interaction, a liquid chromatography-electrospray ionization-tandem mass
      spectrometry assay was developed for the quantitation of low concentrations of
      these compounds in human plasma, using newly synthesized deuterated analogs as
      internal standards. Inhibition constant (K(I)) values were determined for the
      inhibition of (S)-warfarin 7-hydroxylation in human liver microsomes by the
      parent drug and its metabolites, and the unbound drug fractions (f(u)) were
      measured in order to calculate the ratio of unbound plasma concentration to the
      microsomal K(I) for the unbound drug ([I](u)/K(I,u)). From these ratios, we
      predict that a minor metabolite of amiodarone, namely, N,N-didesethylamiodarone
      (DDEA), is a major contributor to the interaction between warfarin and
      amiodarone.

PMID- 22398968
TI  - Bridging strategies for drug combinations in pediatric indications.
AB  - Concurrent prescription of different drugs is common and is often necessary in
      many pediatric indications. A randomized concentration-controlled trial (RCCT) is
      proposed for pediatric studies in which drug combinations are used. The aim of
      our investigation was to show the relevance of flexible designs for accurate dose
      selection in such cases. We used the combination of atovaquone (ATV) and
      proguanil (PGN) as a paradigm to illustrate our approach. Pharmacokinetic models
      were developed for ATV and PGN using data pertaining to adults. The median area
      under the curve (AUC) in adults was considered the target exposure for bridging
      purposes. A pediatric population was simulated according to scenarios in which
      clearance varied from 20 to 100% of the reference adult values or allometrically
      correlated with body weight (BW). Doses were subsequently adapted according to
      the individual AUC estimates. Our results show that adaptive protocols are
      critical for accurate dose selection when evaluating drug combinations in
      children, ensuring that target exposure is achieved with respect to both active
      moieties in each individual patient.

PMID- 22398969
TI  - Prediction of codeine toxicity in infants and their mothers using a novel
      combination of maternal genetic markers.
AB  - Substantial variation exists in response to standard doses of codeine ranging
      from poor analgesia to life-threatening central nervous system (CNS) depression.
      We aimed to discover the genetic markers predictive of codeine toxicity by
      evaluating the associations between polymorphisms in cytochrome P450 2D6
      (CYP2D6), UDP-glucuronosyltransferase 2B7 (UGT2B7), P-glycoprotein (ABCB1), mu
      opioid receptor (OPRM1), and catechol O-methyltransferase (COMT) genes, which are
      involved in the codeine pathway, and the symptoms of CNS depression in 111
      breastfeeding mothers using codeine and their infants. A genetic model combining
      the maternal risk genotypes in CYP2D6 and ABCB1 was significantly associated with
      the adverse outcomes in infants (odds ratio (OR) 2.68; 95% confidence interval
      (CI) 1.61-4.48; P(trend) = 0.0002) and their mothers (OR 2.74; 95% CI 1.55-4.84;
      P(trend) = 0.0005). A novel combination of the genetic and clinical factors
      predicted 87% of the infant and maternal CNS depression cases with a sensitivity
      of 80% and a specificity of 87%. Genetic markers can be used to improve the
      outcome of codeine therapy and are also probably important for other opioids
      sharing common biotransformation pathways.

PMID- 22398971
TI  - Advances in imaging to support the development of novel therapies for multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is a common neurological disease in North America and
      Europe. Although most patients develop major locomotor disability over the course
      of 15-20 years, in approximately one-third of patients the long-term course is
      favorable, with minimal disability. Although current disease-modifying treatments
      reduce the relapse rate, their long-term effects are uncertain. MS treatment
      trials are challenging because of the variable clinical course and typically slow
      evolution of the disease. Magnetic resonance imaging (MRI) is sensitive in
      monitoring MS pathology and facilitates evaluation of potential new treatments.
      MRI measurements of lesion activity have identified new immunomodulatory
      treatments for preventing relapse. Quantitative measurements of tissue volume and
      structural integrity, capable of detecting neuroprotection and repair, should
      facilitate new treatments designed to prevent irreversible disability. Higher
      field MR scanners and new positron emission tomography (PET) radioligands are
      providing new insights into cellular and pathophysiological abnormalities, and
      should be valuable in future therapeutic trials. Retinal axonal loss measured
      using optical coherence tomography (OCT) can assess acute neuroprotection in
      optic neuritis.

PMID- 22398970
TI  - Mechanism of efavirenz influence on methadone pharmacokinetics and
      pharmacodynamics.
AB  - Mechanisms by which efavirenz diminishes methadone plasma concentrations are
      unknown. This investigation determined efavirenz influence on clinical methadone
      disposition and miosis, intravenous and oral alfentanil clearance (hepatic and
      intestinal cytochrome P450 3A4/5 (CYP3A4/5) activity), fexofenadine disposition
      (intestinal transporters activity), and efavirenz clearance and 8-hydroxylation
      (CYP2B6 activity), and human hepatocyte effects. Efavirenz induced systemic and
      oral alfentanil clearances two- to fivefold and induced efavirenz 8
      hydroxylation. Efavirenz stereoselectively decreased methadone plasma
      concentrations 50-70%. Methadone systemic and oral clearances, hepatic clearance
      and extraction ratio, N-demethylation, and metabolite formation clearance were
      stereoselectively increased two- to threefold. Bioavailability decreased.
      Efavirenz shifted methadone concentration-miosis curves leftward and upward.
      Efavirenz induced hepatocyte CYP2B6 and CYP3A4 expression, activity, and
      methadone N-demethylation. Results show that efavirenz coinduced hepatic CYP2B6
      and CYP3A4/5, coinduced hepatic and intestinal CYP3A4/5, and coinduced
      gastrointestinal CYP3A4/5 and efflux transporters. Methadone disposition was most
      consistent with efavirenz induction of hepatic CYP2B6-mediated methadone N
      demethylation. Efavirenz may alter methadone pharmacodynamics.

PMID- 22398972
TI  - Optimization of pediatric rheumatology therapeutics.
AB  - Therapeutics used in pediatric rheumatology have evolved substantially over the
      past few decades; they currently target specific cytokines that are known to be
      involved in the pathophysiology of these complex diseases. The field is limited
      by a lack of full understanding of the etiology and pathophysiology of these
      conditions, as well as by the rarity of these diseases in the pediatric
      population. Advances in biomarkers, pharmacogenomics, and biologic therapies,
      along with a more unified effort from clinicians and investigators, have enabled
      continued growth in the field, fostering the hope for the most effective and
      appropriate therapeutics for pediatric patients.

PMID- 22398973
TI  - The elevation in circulating anti-angiogenic factors is independent of markers of
      neutrophil activation in preeclampsia.
AB  - BACKGROUND: Severe preeclampsia is associated with increased neutrophil
      activation and elevated serum soluble endoglin (sEng) and soluble Flt-1 (sFlt-1)
      in the maternal circulation. To dissect the contribution of systemic inflammation
      and anti-angiogenic factors in preeclampsia, we investigated the relationships
      between the circulating markers of neutrophil activation and anti-angiogenic
      factors in severe preeclampsia or systemic inflammatory state during pregnancy.
      METHODS AND RESULTS: Serum sEng, sFlt-1, placenta growth factor, interleukin-6
      (IL-6), calprotectin, and plasma alpha-defensins concentrations were measured by
      ELISA in 88 women of similar gestational age stratified as: severe preeclampsia
      (sPE, n = 45), maternal systemic inflammatory response (SIR, n = 16) secondary to
      chorioamnionitis, pyelonephritis or appendicitis; and normotensive controls (CRL,
      n = 27). Neutrophil activation occurred in sPE and SIR, as alpha-defensins and
      calprotectin concentrations were two-fold higher in both groups compared to CRL
      (P < 0.05 for each). IL-6 concentrations were highest in SIR (P < 0.001), but
      were higher in sPE than in CRL (P < 0.01). sFlt-1 (P < 0.001) and sEng (P <
      0.001) were ~20-fold higher in sPE compared to CRL, but were not elevated in SIR.
      In women with sPE, anti-angiogenic factors were not correlated with markers of
      neutrophil activation (alpha-defensins, calprotectin) or inflammation (IL-6).
      CONCLUSIONS: Increased systemic inflammation in sPE and SIR does not correlate
      with increased anti-angiogenic factors, which were specifically elevated in sPE
      indicating that excessive systemic inflammation is unlikely to be the main
      contributor to severe preeclampsia.

PMID- 22398975
TI  - Spectroscopic capture and reactivity of S = 1/2 nickel(III)-oxygen intermediates
      in the reaction of a Ni(II)-salt with mCPBA.
AB  - Ni(III)-intermediates are trapped by EPR and UV/Vis spectroscopy in the reaction
      of a Ni(II) salt with mCPBA. On the basis of their oxo-transfer and hydrogen-atom
      abstraction abilities the intermediates are assigned as the elusive terminal
      Ni(III)-oxo/hydroxo species. The findings suggest that Ni(III)-O(H) moieties are
      viable reactants in oxidation catalysis.

PMID- 22398974
TI  - Corneocyte quantification by NIR densitometry and UV/Vis spectroscopy for human
      and porcine skin and the role of skin cleaning procedures.
AB  - Optical methods of corneocyte quantification during tape stripping experiments on
      the skin are useful tools for the rapid evaluation of the skin penetration
      potential of dermally applied substances. However, a comparative investigation of
      the different methods proposed for this task, namely NIR densitometry and UV/Vis
      spectroscopy, is still missing. Thus, the aim of the present work was to employ
      these two techniques in comparative tape stripping experiments both in vivo on
      human forearm skin and in vitro on porcine ear skin. Standard tape stripping
      experiments were performed in the absence and presence of a marketed formulation
      containing flufenamic acid as a model drug. In the context of these
      methodological investigations, different methods of skin cleaning prior to the
      tape stripping procedure were evaluated to identify the most appropriate working
      protocol among the approaches proposed in the respective literature. The results
      showed that the investigated methods of NIR densitometry and UV/Vis spectroscopy
      deliver highly comparable results. Both optical methods are suitable to determine
      the skin penetration profiles of active substances during in vivo and in vitro
      tape stripping, especially if a simple working protocol without any cleaning
      procedures is maintained.

PMID- 22398976
TI  - Neural bases of gaze and emotion processing in children with autism spectrum
      disorders.
AB  - Abnormal eye contact is a core symptom of autism spectrum disorders (ASD), though
      little is understood of the neural bases of gaze processing in ASD. Competing
      hypotheses suggest that individuals with ASD avoid eye contact due to the anxiety
      provoking nature of direct eye gaze or that eye-gaze cues hold less interest or
      significance to children with ASD. The current study examined the effects of gaze
      direction on neural processing of emotional faces in typically developing (TD)
      children and those with ASD. While undergoing functional magnetic resonance
      imaging (fMRI), 16 high-functioning children and adolescents with ASD and 16 TD
      controls viewed a series of faces depicting emotional expressions with either
      direct or averted gaze. Children in both groups showed significant activity in
      visual-processing regions for both direct and averted gaze trials. However, there
      was a significant group by gaze interaction such that only TD children showed
      reliably greater activity in ventrolateral prefrontal cortex for direct versus
      averted gaze. The ASD group showed no difference between direct and averted gaze
      in response to faces conveying negative emotions. These results highlight the key
      role of eye gaze in signaling communicative intent and suggest altered processing
      of the emotional significance of direct gaze in children with ASD.

PMID- 22398977
TI  - Comparison of weight changes following unilateral and staged bilateral STN DBS
      for advanced PD.
AB  - Unilateral and bilateral subthalamic nucleus deep brain stimulation (STN DBS) in
      Parkinson's disease (PD) result in weight gain in the initial postoperative
      months, but little is known about the changes in weight following unilateral and
      staged bilateral STN DBS over longer time intervals. A case-control comparison
      evaluated weight changes over 2 years in 43 consecutive unilateral STN DBS
      patients, among whom 25 elected to undergo staged bilateral STN DBS, and 21 age
      matched and disease severity matched PD controls without DBS. Regression analyses
      incorporating age, gender, and baseline weight in case or control were conducted
      to assess weight changes 2 years after the initial unilateral surgery. Unilateral
      STN DBS and staged bilateral STN DBS patients gained 3.9 +/- 2.0 kg and 5.6 +/-
      2.1 kg versus their preoperative baseline weight (P < 0.001, respectively) while
      PD controls without DBS lost 0.8 +/- 1.1 kg. Although bilateral STN DBS patients
      gained 1.7 kg more than unilateral STN DBS patients at 2 years, this difference
      was not statistically significant (P = 0.885). Although there was a trend toward
      greater weight gain in staged bilateral STN DBS patients versus unilateral
      patients, we found no evidence for an equivalent or synergistic increase in body
      weight following placement of the second DBS electrode.

PMID- 22398978
TI  - Gaze and viewing angle influence visual stabilization of upright posture.
AB  - Focusing gaze on a target helps stabilize upright posture. We investigated how
      this visual stabilization can be affected by observing a target presented under
      different gaze and viewing angles. In a series of 10-second trials, participants
      (N = 20, 29.3 +/- 9 years of age) stood on a force plate and fixed their gaze on
      a figure presented on a screen at a distance of 1 m. The figure changed position
      (gaze angle: eye level (0 degrees ), 25 degrees  up or down), vertical body
      orientation (viewing angle: at eye level but rotated 25 degrees  as if leaning
      toward or away from the participant), or both (gaze and viewing angle: 25 degrees
      up or down with the rotation equivalent of a natural visual perspective).
      Amplitude of participants' sagittal displacement, surface area, and angular
      position of the center of gravity (COG) were compared. Results showed decreased
      COG velocity and amplitude for up and down gaze angles. Changes in viewing angles
      resulted in altered body alignment and increased amplitude of COG displacement.
      No significant changes in postural stability were observed when both gaze and
      viewing angles were altered. Results suggest that both the gaze angle and viewing
      perspective may be essential variables of the visuomotor system modulating
      postural responses.

PMID- 22398979
TI  - A cytokine mixture of GM-CSF and IL-3 that induces a neuroprotective phenotype of
      microglia leading to amelioration of (6-OHDA)-induced Parkinsonism of rats.
AB  - Dopamine (DA) agonists are widely used as primary treatments for Parkinson's
      disease. However, they do not prevent progressive degeneration of dopaminergic
      neurons, the central pathology of the disease. In this study, we found that
      subcutaneous injection of a cytokine mixture containing granulocyte macrophage
      colony-stimulating factor and interleukin-3 (IL-3) markedly suppressed
      dopaminergic neurodegeneration in 6-hydroxydopamine-lesioned rats, an animal
      model of Parkinson's disease. The cytokine mixture suppressed the decrease of DA
      content in the striatum, and ameliorated motor function in the lesioned rats. In
      response to the cytokine injection, dopaminergic neurons in the substantia nigra
      pars compacta increased expression of the antiapoptotic protein Bcl-xL.
      Microglial activation in the pars compacta was evident in both the saline- and
      cytokine-injected rats. However, the cytokine mixture suppressed expression of
      the proinflammatory cytokines IL-1beta and tumor necrosis factors alpha, and
      upregulated the neuroprotective factors insulin-like growth factor-1 and
      hepatocyte growth factor. Similar responses were observed in cultured microglia.
      Detailed morphometric analyses revealed that NG2 proteoglycan-expressing glial
      cells increased in the cytokine-injected rats, while astrocytic activation with
      increased expression of antioxidative factors was evident only in the saline
      injected rats. Thus, the present findings show that the cytokine mixture was
      markedly effective in suppressing neurodegeneration. Its neuroprotective effects
      may be mediated by increased expression of Bcl-xL in dopaminergic neurons, and
      the activation of beneficial actions of microglia that promote neuronal survival.
      Furthermore, this cytokine mixture may have indirect actions on NG2 proteoglycan
      expressing glia, whose role may be implicated in neuronal survival.

PMID- 22398981
TI  - Eye-of-the-Tiger sign is not Pathognomonic of Pantothenate Kinase-Associated
      Neurodegeneration in Adult Cases.
AB  - An eye-of-the-tiger sign is previously known to have one-to-one correlation with
      pantothenate kinase-associated neurodegeneration (PKAN). Reviewing the literature
      on this subject, the correlation between eye-of-the-tiger sign and PKAN seems to
      show an interesting hypothesis that differs from conventional conclusion. We
      analyze the published papers in an attempt to reflect this trend and illustrate
      our points with findings in a 39-year-old man. His brain magnetic resonance
      imaging study shows typical eye-of-the-tiger sign suggestive of PKAN. Genetic
      analyses revealed no mutations in pantothenate kinase 2.

PMID- 22398980
TI  - Epidemic of illicit drug use, mechanisms of action/addiction and stroke as a
      health hazard.
AB  - Drug abuse robs individuals of their jobs, their families, and their free will as
      they succumb to addiction; but may cost even more: a life of disability or even
      life lost due to stroke. Many illicit drugs have been linked to major
      cardiovascular events and other comorbidities, including cocaine, amphetamines,
      ecstasy, heroin, phencyclidine, lysergic acid diethylamide, and marijuana. This
      review focuses on available epidemiological data, mechanisms of action,
      particularly those leading to cerebrovascular events, and it is based on papers
      published in English in PubMed during 1950 through February 2011. Each drug's
      unique interactions with the brain and vasculature predispose even young, healthy
      people to ischemic or hemorrhagic stroke. Cocaine and amphetamines have the
      strongest association with stroke. However, the level of evidence firmly linking
      other drugs to stroke pathogenesis is weak. Large epidemiological studies and
      systematic evaluation of each drug's action on the brain and cardiovascular
      system are needed to reveal the full impact of drug use on the population.

PMID- 22398983
TI  - Publishing in an open access age: preserving the scribbles, getting heard, and
      assuring the quality of information.

PMID- 22398982
TI  - Challenges in diagnosis of isolated central nervous system vasculitis.
AB  - Isolated central nervous system (CNS) vasculitis is a rare and complicated
      disorder. Patients typically present with nonspecific neurologic symptoms such as
      headache and encephalopathy, and have variable progression and severity of the
      disease. Challenges to definitive diagnosis include the limitations of currently
      available diagnostic modalities with high likelihood of false-positive or false
      negative findings. Imaging, serologic, and cerebrospinal fluid (CSF) evaluation,
      and even angiography can fail to establish the diagnosis. Often, brain biopsy is
      required. In order to illustrate these challenges, we report the case of a
      patient who presented with subacute cognitive decline and was ultimately
      diagnosed with isolated CNS eosinophilic vasculitis. Initial work-up included CSF
      and serologic analyses, magnetic resonance imaging (MRI), and cerebral
      angiography, but definitive diagnosis required brain biopsy. Immunosuppressive
      therapy resulted in clinical improvement and stabilization. To our knowledge,
      only one other case of isolated CNS eosinophilic vasculitis has been reported in
      the literature. We discuss the importance of a high index of clinical suspicion
      in cases of progressive nonspecific neurologic symptoms.

PMID- 22398985
TI  - The molecular underpinnings of a solute-pump/solvent-probe spectroscopy: the
      theory of polarizability response spectra and an application to preferential
      solvation.
AB  - Recent ultrafast experiments on liquids have made clear that it is possible to go
      beyond light scattering techniques such as optical Kerr spectroscopy that look at
      the dynamics of a liquid as a whole. It is now possible to measure something far
      more conceptually manageable: how that liquid dynamics (and that light
      scattering) can be modified by electronically exciting a solute. Resonant-pump
      polarizability-response spectra (RP-PORS) in particular, seem to show that
      different solvents respond in noticeably distinct ways to such solute
      perturbations. This paper is a theoretical attempt at understanding the kinds of
      molecular information that can be revealed by experiments of this sort. After
      developing the general classical statistical mechanical linear response theory
      for these spectra, we show that the experimentally interesting limit of long
      solute-pump/solvent-probe delays corresponds to measuring the differences in 4
      wave-mixing spectra between solutions with equilibrated ground- and excited-state
      solutes-meaning that the spectra are essentially probes of how changing liquid
      structure affects intermolecular liquid vibrations and librations. We examine the
      spectra in this limit for the special case of an atomic solute dissolved in an
      atomic-liquid mixture, a preferential solvation problem, and show that, as with
      the experimental spectra, different solvents can lead to spectra with different
      magnitudes and even different signs. Our molecular-level analysis of these
      results points out that solvents can also differ in how local a portion of the
      solvent dynamics is accessed by this spectroscopy.

PMID- 22398984
TI  - Methanol extract of Bauhinia purpurea leaf possesses anti-ulcer activity.
AB  - OBJECTIVE: The aim of the present study was to determine the anti-ulcer activity
      of a methanol extract of Bauhinia purpurea leaf (MEBP). MATERIALS AND METHODS:
      MEBP was administered at doses of 100, 500 and 1,000 mg/kg and its effects on
      acute toxicity, absolute ethanol- and indomethacin-induced gastric ulceration,
      and pyloric ligation tests in rats were investigated. RESULTS: At a dose of 5,000
      mg/kg, MEBP did not cause any signs of toxicity in rats when given orally. Oral
      administration of MEBP exerted anti-ulcer activity (p < 0.05) in all models
      tested. However, a dose-dependent protection was observed only in the
      indomethacin-induced gastric ulceration model. Histological studies supported the
      observed anti-ulcer activity of MEBP. In the pyloric ligation assay, MEBP
      significantly increased gastric wall mucus secretion (p < 0.05), but did not
      affect the acidity of the gastric contents. CONCLUSION: MEBP exhibited anti-ulcer
      activity, which could be due to the presence of flavonoids, saponins or other
      polyphenols, thereby validating the traditional use of B. purpurea in the
      treatment of ulcers.

PMID- 22398986
TI  - Tumors and proliferative lesions in adult offspring after maternal exposure to
      methylarsonous acid during gestation in CD1 mice.
AB  - Developmental exposure to inorganic arsenic is carcinogenic in humans and mice,
      and adult offspring of mice exposed to inorganic arsenic can develop tumors of
      the lung, liver, adrenal, uterus, and ovary. It has been suggested that
      methylarsonous acid (MMA3+), a product of the biological methylation of inorganic
      arsenic, could be a key carcinogenic species. Thus, pregnant CD1 mice were
      provided drinking water containing MMA3+ at 0 (control), 12.5, or 25 parts per
      million (ppm) from gestational days 8 to 18. Tumors were assessed in groups of
      male or female (initial n = 25) offspring up to 2 years of age. In utero
      treatment had no effect on survival or body weights. Female offspring exhibited
      increases in total epithelial uterine tumors (control 0%; 12.5 ppm 26%; 25 ppm
      30%), oviduct hyperplasia (control 4%; 12.5 ppm 35%; 25 ppm 43%), adrenal
      cortical adenoma at 25 ppm (control 0%; 12.5 ppm 9%; 25 ppm 26%), and total
      epithelial ovarian tumors (control 0%; 12.5 ppm 39%; 25 ppm 26%). Male offspring
      showed dose-related increases in hepatocellular carcinoma (control 0%; 12.5 ppm
      12%; 25 ppm 22%), adrenal adenoma (control 0%; 12.5 ppm 28%; 25 ppm 17%), and
      lung adenocarcinoma (control 17%; 12.5 ppm 44%). Male offspring had unusual
      testicular lesions, including two rete testis carcinomas, two adenomas, and three
      interstitial cell tumors. Overall, maternal consumption of MMA3+ during pregnancy
      in CD1 mice produced some similar proliferative lesions as gestationally applied
      inorganic arsenic in the offspring during adulthood.

PMID- 22398987
TI  - The diversity of actinorhizal symbiosis.
AB  - Filamentous aerobic soil actinobacteria of the genus Frankia can induce the
      formation of nitrogen-fixing nodules on the roots of a diverse group of plants
      from eight dicotyledonous families, collectively called actinorhizal plants.
      Within nodules, Frankia can fix nitrogen while being hosted inside plant cells.
      Like in legume/rhizobia symbioses, bacteria can enter the plant root either
      intracellularly through an infection thread formed in a curled root hair, or
      intercellularly without root hair involvement, and the entry mechanism is
      determined by the host plant species. Nodule primordium formation is induced in
      the root pericycle as for lateral root primordia. Mature actinorhizal nodules are
      coralloid structures consisting of multiple lobes, each of which represents a
      modified lateral root without a root cap, a superficial periderm and with
      infected cells in the expanded cortex. In this review, an overview of nodule
      induction mechanisms and nodule structure is presented including comparisons with
      the corresponding mechanisms in legume symbioses.

PMID- 22398988
TI  - Condom use by partner type among military and police personnel in Peru.
AB  - The aim of this study was to analyze the rates of condom use among military and
      police populations in Peru, focusing on differences in use by type of partner. A
      Knowledge Attitudes and Practices survey was conducted among 6,808 military and
      police personnel in 18 Peruvian cities between August-September 2006 and
      September-October 2007. A total of 90.2% of the survey respondents were male;
      mean age was 37.8 years and 77.9% were married/cohabiting. In all, 99.5% reported
      having had sex; 89% of the participants had their last sexual contact with their
      stable partner, 9.7% with a nonstable partner, and 0.8% with a sex worker.
      Overall, 20.4% used a condom during their most recent sexual contact. Reasons for
      nonuse of condoms included the following: perception that a condom was not
      necessary (31.3%) and using another birth control method (26.7%). Prevention
      efforts against sexually transmitted diseases should focus on strengthening
      condom use, especially among individuals with nonstable partners.

PMID- 22398989
TI  - Predictors of serum vitamin D levels in African American and European American
      men in Chicago.
AB  - Vitamin D deficiency is epidemiologically linked to prostate, breast, and colon
      cancer. When compared with European American (EA) men, African American (AA) men
      have increased risk of prostate cancer, but few studies evaluate vitamin D status
      in AA men. The authors evaluate the biological and environmental predictors of
      vitamin D deficiency in AA and EA men in Chicago, Illinois, a low ultraviolet
      radiation environment. Blood samples were collected from 492 men, aged between 40
      and 79 years, from urology clinics at three hospitals in Chicago, along with
      demographic and medical information, body mass index, and skin melanin content
      using a portable narrow-band reflectometer. Vitamin D intake and ultraviolet
      radiation exposure were assessed using validated questionnaires. The results
      demonstrated that Black race, cold season of blood draw, elevated body mass
      index, and lack of vitamin D supplementation increase the risk of vitamin D
      deficiency. Supplementation is a high-impact, modifiable risk factor. Race and
      sunlight exposure should be taken into account for recommended daily allowances
      for vitamin D intake.

PMID- 22398990
TI  - Perceptions of HIV risk among internet-using, HIV-negative barebacking men.
AB  - The current study examines the risk perceptions of HIV-negative men who have sex
      with men (MSM) who use the Internet to seek unprotected sex. The research
      questions include the following: How great do these men perceive their HIV risk
      to be? Are their perceptions based on HIV knowledge or related to their risk
      behaviors? What factors are associated with greater/lesser perceived risk?
      Results revealed that more than half of the men believed that they had no or only
      a slight chance of contracting HIV. Risk perceptions were not related to HIV
      knowledge or to involvement in HIV risk practices. Four factors were identified
      as being associated with greater perception of HIV risk: self-identity as a
      sexual "bottom," having sex while high, greater use of bareback-focused websites,
      and younger age. Internet-using HIV-negative men who have sex with men tend to
      underestimate their risk for acquiring HIV, and interventions need to help them
      accurately assess their risk.

PMID- 22398991
TI  - Barbershops as venues to assess and intervene in HIV/STI risk among young,
      heterosexual African American men.
AB  - African Americans, particularly men, are disproportionately affected by the HIV
      epidemic. Inconsistent condom use and concurrent sexual partnerships are risk
      factors; there is limited investigation on how these factors influence HIV risk
      engagement in young, heterosexual, African American men. To identify contextual
      risk factors that place young men (18-24 years) at risk for HIV infection, one
      focus group was conducted with 13 men, and questionnaires were administered to 48
      men. Participants were 18 to 24 years old and were recruited from local
      barbershops. The majority engaged in noncondom use (83%) and had multiple sexual
      partners (64%). Qualitative themes revealed noncondom use "when in the moment"
      and enhanced condom use with casual partners. This study provided an
      understanding of participants' attitudes, intentions, and behaviors as they
      related to HIV risk and revealed the need for culturally relevant, theory-based
      HIV prevention programs to reduce HIV transmission among this population.

PMID- 22398992
TI  - Providers' attitudes toward human papillomavirus vaccination in young men:
      challenges for implementation of 2011 recommendations.
AB  - Providers' attitudes toward male human papillomavirus (HPV) vaccination may
      influence the implementation of new guidelines. Although 24 of 31 (77%) Pediatric
      and Family Medicine providers interviewed between 2009 and 2010 favored
      vaccinating males, only 3 (12%) offered vaccination. Providers who did not offer
      vaccination felt that parents would not be interested in vaccinating sons and
      were largely unaware of serious HPV-related disease in males.

PMID- 22398993
TI  - Psychological distress among employed fathers: associations with family
      structure, work quality, and the work-family interface.
AB  - The aim of this study was to compare levels of psychological distress in employed
      single fathers relative to partnered fathers and to explore the role of
      psychosocial job quality, work-family conflict, and work-family facilitation as
      explanations for differences in distress. The data were collected from a cross
      sectional telephone survey conducted in a Canadian city. Participants were 486
      employed fathers with children living in the household. In addition to
      experiencing higher levels of psychological distress than partnered fathers (p =
      .057), single fathers reported greater work-family conflict, poorer work quality,
      and lower family-to-work facilitation. Adjusting for the strain-based work-family
      conflict variables in the regression analysis resulted in the largest reduction
      to the association between partner status and psychological distress. Future
      research employing a longitudinal design and subject to lower selection biases is
      required to tease out the interrelationship between these exposures and to point
      to the most appropriate policies to support employed single fathers.

PMID- 22398994
TI  - Male perpetrators, the gender symmetry debate, and the rejection-abuse cycle:
      implications for treatment.
AB  - This review article examined the gender symmetry debate in light of recent
      research relating to the feminist and family research perspectives on intimate
      partner violence, providing a context for rethinking perpetrator programs. The
      concept of coercive control is considered as an explanatory factor in an attempt
      to integrate the feminist and family research perspectives. The limited
      effectiveness of perpetrator programs is examined. Research highlighting
      potential factors that could improve the effectiveness of perpetrator programs is
      introduced, followed by a discussion of the rejection-abuse cycle, one attempt to
      incorporate current research into a more inclusive program. The rejection-abuse
      cycle identifies a pattern of perpetrator behavior, which links rejection, threat
      to self, defense against threat, and abuse. Finally, suggestions for changing
      perpetrator programs are elaborated, incorporating past research, which would
      make them appropriate for both male and female perpetrators. These implications
      are contextualized within a meta-theory to provide greater clarity for the
      development of future perpetrator programs.

PMID- 22398995
TI  - The implications of increasing age on erectile dysfunction.
AB  - Erectile dysfunction (ED) has long been correlated with psychological well-being.
      More recently, an understanding has developed of ED being, in some cases, a
      vascular condition of the penile artery. Given the narrowness of the penile
      artery, a small amount of atherosclerosis may result in ED before any other
      manifestations are evident, making ED a useful marker for other vascular
      conditions with potentially greater clinical implications. In light of this,
      possible underreporting of ED takes on added significance. A questionnaire
      regarding ED prevalence and management was distributed for self-administration to
      men in the waiting room of primary care clinics; the data were analyzed with a
      focus on the relationship between ED and age. The study had a remarkable response
      rate of >95%. The prevalence of ED in the >=70-year age-group was 77%, compared
      with 61% in the 40- to 69-year age-group (p = .0001). ED correlated linearly with
      age (R(2) = .80, p < .0001). Among those who had ED, more than half had not
      discussed it with any provider; the likelihood of discussing ED did increase with
      the reported severity of symptoms (p < .0001). Older men had more severe ED than
      younger men (p < .0001). Furthermore, 72% of men with a history of ED were never
      treated. Younger men were more likely to be treated than older men (p = .004).
      Given the potential implications of underreporting ED, and the willingness of the
      men in this study to complete the questionnaire, further work may be merited on
      new models for ED assessment and follow-up.

PMID- 22398996
TI  - Called to account: NMC review underway.

PMID- 22398997
TI  - Children's haemangiomas: use of new topical therapies.

PMID- 22398998
TI  - Palliative care nursing for children in the UK and Ireland.
AB  - Currently, there are many changes taking place in the area of paediatric
      palliative care. These include the role of the nurse, development of national
      policies, and recommendations for the future of paediatric palliative care. This
      article discusses palliative care for children with life-limiting conditions in
      the UK and Ireland, highlights national and international developments in this
      area, describes current services, and makes recommendations for future
      developments. Paediatric palliative care should be holistic, family centred and
      tailored to meet the needs of each child and family. Palliative care should
      promote autonomy and allow informed choices regarding end-of-life care.
      Palliative care should begin at the time of diagnosis and continue beyond
      illness, through the bereavement process. It should be adaptable to allow care
      delivery in any setting; home, hospice or hospital. Health professionals
      providing paediatric palliative care should be appropriately trained in this
      specialist field and the best interests of the child should always be at the
      forefront of care.

PMID- 22398999
TI  - The Sexual Offences (NI) Order 2008: implications for nurses.
AB  - This article outlines the changes to the definition of sexual offences in
      Northern Ireland following the implementation of the Sexual Offences Northern
      Ireland Order 2008 in 2009, and its implications for nurses working with sexually
      active children in a range of clinical settings. The paper outlines the key
      changes for practice and addresses the needs of children in three different age
      groups with emphasis on children aged 13-15 years, and reviews mandatory
      reporting, the difference between the rights of children to consent and
      confidentiality, developmental sexual experimentation and sexual health
      protection. It reviews related policy and guidance and makes clear the
      differences between sexual abuse and exploitation, and experimentation. It seeks
      to advise the Safeguarding Committee of the Department of Health Northern Ireland
      on how best to support nurses working with sexually active children and when this
      activity should be discussed with line managers and safeguarding specialists or
      referred to the safeguarding authorities.

PMID- 22399000
TI  - Smoking behaviour and interaction: the observation process in research.
AB  - To those starting off on the research journey, the term 'qualitative research'
      can often seem a daunting prospect. The world of research methodology and theory
      is emerged in a rich history of its own terminology, meanings and experiences.
      Research and innovation are integral parts of the nurse practitioner's role, yet
      many have little understanding of the theoretical frameworks and methodologies
      surrounding the vast areas of qualitative and quantitative research. As part of a
      doctorate, the author undertook a small qualitative study, choosing her own
      method and question. Intrigued by the phenomenon of smoking addiction, she
      observed the behaviours and interactions of people who smoke. The focus of this
      article, however, is the process by which the study was carried out, rather than
      the observations themselves. This paper presents observational research from the
      perspective of a nurse practitioner embarking on a journey with qualitative
      designs.

PMID- 22399001
TI  - Ethical challenges of conducting health research in UK school setting.
AB  - This paper offers guidance for novice nurse researchers on the ethical and
      methodological challenges of conducting health research in high school settings.
      Over the course of two studies in UK high schools with students aged 11-16 years,
      the authors encountered common ethical and methodological challenges. This
      article draws on these studies to build a critique of approaches to health
      research in school settings. Issues of consent and assent, confidentiality and
      participation can highlight tensions between the expectations of schools and
      health researchers. In this context, feasible research designs raise complex
      ethical and methodological questions. Ethical and methodological norms for health
      research may not be suitable for high school settings. Successful school-based
      health research designs may need to be flexible and responsive to the social
      environment of schools.

PMID- 22399002
TI  - Use of bullying as a management tool in healthcare environments.
AB  - Bullying is very much an aspect of contemporary society and perhaps it always has
      been. Many may have experienced it from early childhood while at school, either
      as victims or perpetrators. The healthcare industry is, sadly, not immune from
      this phenomenon. This short article seeks to answer the question: 'Is bullying
      deliberately used as a management tool within the healthcare industry?' Although
      bullies exist in many healthcare environments, and there may be a culture of
      bullying in some of these work places, the proposition that some people actually
      use bullying as a management tool is more difficult to prove.

PMID- 22399003
TI  - Striking the balance: night care versus the facilitation of good sleep.
AB  - This article presents the key findings from an extensive research project aiming
      to identify the determinants of poor sleep in care homes. A mixed methods study
      was conducted in 10 care homes in South East England. This included 2-week daily
      diaries completed by 145 older residents and interviews with 50 care-home staff.
      This research demonstrated that the regular surveillance by qualified nurses and
      care assistants at night seriously impedes the quality of sleep experienced by
      older people living in care homes. However, nurses and social care workers have a
      duty of care, which would not be fulfilled if regular checks were not undertaken
      at night. There is a need for care-home staff to strike a balance between
      enabling older people living in care homes to have a good night's sleep and
      adhering to their own professional duty of care.

PMID- 22399004
TI  - Sex selection and abortion: a case  for legal re-evaluation?
AB  - This question of sex selection and abortion in the UK was highlighted by recent
      reports in a national newspaper. This paper explores the current legal position
      and whether there is a case for reforming the law to align the situation of
      abortion with that of sex selection in the context of pre-implantation genetic
      diagnosis.

PMID- 22399005
TI  - Attrition rates:   the student perspective.

PMID- 22399006
TI  - Professional development:  from staff nurse to nurse consultant.  Part 6:
      importance of role models.

PMID- 22399007
TI  - Can nurses stem the rising  tide of alcohol abuse?

PMID- 22399008
TI  - Challenges in patient safety and health quality.

PMID- 22399009
TI  - The Health and Social Care Bill: value for money or service improvement?
AB  - Over the past couple of weeks, I have found myself yet again examining the
      proposed new Health and Social Care Bill. Although the Bill has cleared the House
      of Commons for now, it is being scrutinized in the House of Lords, who have had
      plenty of critical and uncomplimentary things to say. My concern regarding the
      progress of the Bill and the negative response surrounding it prompted me to
      revisit the legislation.

PMID- 22399010
TI  - L-ficolin binds to the glycoproteins hemagglutinin and neuraminidase and inhibits
      influenza A virus infection both in vitro and in vivo.
AB  - L-ficolin, one of the complement lectins found in human serum, is a novel pattern
      recognition molecule that can specifically bind to microbial carbohydrates,
      thereby activating the lectin complement pathway and mounting a protective innate
      immune response. However, little is known about the role of L-ficolin during
      viral infections in vivo. In the present study, we used a mouse model of
      influenza A virus infection to demonstrate that the administration of exogenous L
      ficolin or ficolin A (FCNA - an L-ficolin-like molecule in the mouse) is
      protective against the virus. Furthermore, FCNA-null mice have a greatly
      increased susceptibility to infection with the influenza A virus. Moreover, we
      found recombinant human L-ficolin inhibited influenza A virus entry into Madin
      Darby canine kidney cells. More importantly, L-ficolin can recognize and bind
      hemagglutinin (HA) and neuraminidase (NA) glycoproteins and different subtypes of
      influenza A virus, and these interactions can be competitively inhibited by N
      acetyl-D-glucosamine. In addition, the binding of L-ficolin and FCNA may lead to
      the activation of the lectin complement pathway. To our knowledge, this is the
      first report demonstrating that L-ficolin can block influenza virus infections
      both in vitro and in vivo using FCNA-knockout mice, possibly by interacting with
      the carbohydrates of HA and NA. Therefore, these data may provide new
      immunotherapeutic strategies based on the innate immune molecule L-ficolin
      against the influenza A virus.

PMID- 22399011
TI  - Interpretation of serum calcitonin in patients with chronic autoimmune
      thyroiditis.
AB  - Calcitonin (CT) is an important clinical marker for the diagnosis and follow-up
      of medullary thyroid carcinoma, although it is not absolutely specific. Some
      authors have reported C-cell hyperplasia in a number of thyroid specimens
      affected by Hashimoto's thyroiditis. The association between thyroiditis and
      hypercalcitoninemia is still controversial because some authors have reported low
      CT levels. The aim of this study is to evaluate the basal CT values in patients
      with and without thyroid autoimmunity. From May 2005 to February 2010, 1073
      patients underwent ultrasonography-guided fine-needle aspiration cytology at the
      Thyroid Center of Sapienza University of Rome, with evaluation of basal serum
      FT4, FT3, TSH, and antithyroid peroxidase (anti-TPO) antibodies as well as CT
      levels. Forty-one patients presented a basal CT level above the reference upper
      limit. The mean serum CT was significantly lower in women than in men (4.28 +/-
      6.63 vs 7.50 +/- 25.50  pg/ml; P<0.01). Basal serum CT was not significantly
      higher in patients showing anti-TPO Ab positivity (4.71 +/- 6.46 vs 4.84 +/-
      13.11  pg/ml; P>0.05). Importantly, the rate of 'suspicious' CT values (above the
      10  pg/ml cutoff) was not significantly different between patients with or
      without thyroid autoimmunity (3.9 vs 3.0%). Patients with hypercalcitoninemia
      suffering from chronic autoimmune thyroiditis should undergo the same clinical
      evaluation procedure as patients do without thyroid autoimmunity.

PMID- 22399012
TI  - Variations of serum testosterone levels in prostate cancer patients under LH
      releasing hormone therapy: an open question.
AB  - The hypothesis 'the lower the better when achieving castration levels of
      testosterone' is based on the data from second-line hormonal manipulation and its
      molecular basis, and on better oncological results reported for lower castration
      levels in prostate cancer (PCa) patients, including those achieved with maximal
      androgen blockade. In this regard, the equivalence of surgical and different
      pharmacological castrations has been controversial. The modified amino acid
      structure that makes LH-releasing hormone (LHRH) analogs more potent than LHRH,
      and the method of delivering the analogs impacts on bioavailibility and
      potentially causes differences in androgen levels and in its final oncological
      efficacy. In addition to this, there is a myriad of circumstances, such as those
      related to ethnic variations and co-morbidities, which uniquely impact on the
      pharmacological approach in a highly heterogeneous population of castration
      resistant prostate cancer (CRPC) patients. Ineffective testosterone suppression
      through hormonal escape is currently poorly recognized and may result in
      increased PCa mortality. Until now, the optimal serum testosterone level in
      patients under castration, and the impact of its variations in patients under
      LHRH therapy, remain open questions and have been merged to a broad spectra of
      patients who are highly heterogeneous. This heterogeneity relates to a number of
      mechanisms regarding response to treatment, which influences the biology of the
      relapsing tumor and the sensitivity to subsequent therapies in the individual
      patient. The rationale to achieve testosterone levels below 20-50 ng/dl warrant
      further investigation as these levels have recently rescued CRPC patients. In the
      last few years and months, important advancements in prostate cancer treatment
      have been achieved. Nevertheless, these advances are measured in a few months of
      additional survival and under high costs, not available to most of the world
      population, compared with the benefits of hormonal manipulation that are measured
      in years, there is a huge potential for accessible and durable effect expansion
      and optimization of treatment, particularly with the current tendency of a more
      individual approach.

PMID- 22399014
TI  - Variability of fibrinogen measurements in post-myocardial infarction patients.
      Results from the AIRGENE study center Augsburg.
AB  - Elevated fibrinogen levels are strongly and consistently associated with incident
      coronary heart disease (CHD). A possible causal contribution of fibrinogen in the
      pathway leading to atherothrombotic cardiovascular disease complications has been
      suggested. However, for implementation in clinical practice, data on validity and
      reliability, which are still scarce, are needed that are still scarce, especially
      in subjects with a history of CHD. For the present study, levels of plasma
      fibrinogen were measured in 200 post-myocardial infarction (post-MI) patients
      aged 39-76 years, with approximately six blood samples collected at monthly
      intervals between May 2003 and March 2004, giving a total of 1,144 samples. Inter
      individual variability (between-subject variance component, VCb and coefficient
      of variation, CVb), intra-individual and analytical variability (VCw+a and
      CVw+a), intraclass correlation coefficient (ICC) and the number of measurements
      required for an ICC of 0.75 were estimated to assess the reliability of serial
      fibrinogen measurements. Mean fibrinogen concentration of all subjects over all
      samples was 3.34 g/l (standard deviation 0.67). Between-subject variation for
      fibrinogen was VCb = 0.34 (CVb'=17.5%) whereas within-subject and analytical
      variation was estimated as VCw+a = 0.14 (CVw+a=11.0%). The variation was mainly
      explained by between-subject variability, shown by the proportion of total
      variance of 71.3%. Two different measurements were required to reach sufficient
      reliability, if subjects with extreme values were not excluded. The present study
      indicates a fairly good reproducibility of serial individual fibrinogen
      measurements in post-MI subjects.

PMID- 22399013
TI  - Therapeutic potential of MEK inhibition in acute myelogenous leukemia: rationale
      for "vertical" and "lateral" combination strategies.
AB  - In hematological malignancies, constitutive activation of the RAF/MEK/ERK pathway
      is frequently observed, conveys a poor prognosis, and constitutes a promising
      target for therapeutic intervention. Here, we investigated the molecular and
      functional effects of pharmacological MEK inhibition in cell line models of acute
      myeloid leukemia (AML) and freshly isolated primary AML samples. The small
      molecule, ATP-non-competitive, MEK inhibitor PD0325901 markedly inhibited ERK
      phosphorylation and growth of several AML cell lines and approximately 70 % of
      primary AML samples. Growth inhibition was due to G(1)-phase arrest and induction
      of apoptosis. Transformation by constitutively active upstream pathway elements
      (HRAS, RAF-1, and MEK) rendered FDC-P1 cells exquisitely prone to PD0325901
      induced apoptosis. Gene and protein expression profiling revealed a selective
      effect of PD0325901 on ERK phosphorylation and compensatory upregulation of the
      RAF/MEK and AKT/p70( S6K ) kinase modules, potentially mediating resistance to
      drug-induced growth inhibition. Consequently, in appropriate cellular contexts,
      both "vertical" (i.e., inhibition of RAF and MEK along the MAPK pathway) and
      "lateral" (i.e., simultaneous inhibition of the MEK/ERK and mTOR pathways)
      combination strategies may result in synergistic anti-leukemic effects. Overall,
      MEK inhibition exerts potent growth inhibitory and proapoptotic activity in
      preclinical models of AML, particularly in combination with other pathway
      inhibitors. Deeper understanding of the molecular mechanisms of action of MEK
      inhibitors will likely translate into more effective targeted strategies for the
      treatment of AML.

PMID- 22399015
TI  - Stapes surgery in osteogenesis imperfecta: retrospective analysis of 34 operated
      ears.
AB  - Intraoperative findings of stapes surgery in 34 ears from 22 patients with
      genetically confirmed osteogenesis imperfecta (OI) are reported, as well as the
      audiometric results after the longest postoperative follow-up published to date.
      Twenty-nine out of 34 ears underwent primary stapes surgery and 5 ears revision
      surgery. Postoperative audiometric follow-up ranged from 6 months to 37 years.
      Stapes footplates were fixed in all ears. Additionally, footplates were thickened
      or fragile, stapes crura atrophic or fractured, and middle ear mucosae thickened
      or hypervascularized. Short-term postoperative audiometry revealed improved
      hearing and reduced air-bone gaps in 28/29 primary operated ears and in all
      revision cases. In the 22 ears with long-term postoperative follow-up (mean
      duration: 16 years), hearing gain was still significant at the latest audiometric
      evaluation. Independently of the patients being diagnosed with OI type I or IV
      and independently of the underlying OI genotype, beneficial results are obtained
      in the majority of OI patients undergoing primary or revision stapes surgery for
      reduction of conductive hearing loss components caused by stapes footplate
      fixation. Despite the progressive course of the concomitant sensorineural
      component, hearing gain remains beneficial over several decades.

PMID- 22399017
TI  - Photoswitchable fluorescent diarylethene in a turn-on mode for live cell imaging.
AB  - A new diarylethene-derived photochromic compound, with little cytotoxicity,
      plasma membrane-permeability, and efficient photoswitchability in cells upon
      alternative UV and visible light irradiation, was synthesized and applied to live
      cell imaging.

PMID- 22399016
TI  - Digital LAMP in a sample self-digitization (SD) chip.
AB  - This paper describes the realization of digital loop-mediated DNA amplification
      (dLAMP) in a sample self-digitization (SD) chip. Digital DNA amplification has
      become an attractive technique to quantify absolute concentrations of DNA in a
      sample. While digital polymerase chain reaction is still the most widespread
      implementation, its use in resource-limited settings is impeded by the need for
      thermal cycling and robust temperature control. In such situations, isothermal
      protocols that can amplify DNA or RNA without thermal cycling are of great
      interest. Here, we accomplished the successful amplification of single DNA
      molecules in a stationary droplet array using isothermal digital loop-mediated
      DNA amplification. Unlike most (if not all) existing methods for sample
      discretization, our design allows for automated, loss-less digitization of sample
      volumes on-chip. We demonstrated accurate quantification of relative and absolute
      DNA concentrations with sample volumes of less than 2 MUl. We assessed the
      homogeneity of droplet size during sample self-digitization in our device, and
      verified that the size variation was small enough such that straightforward
      counting of LAMP-active droplets sufficed for data analysis. We anticipate that
      the simplicity and robustness of our SD chip make it attractive as an inexpensive
      and easy-to-operate device for DNA amplification, for example in point-of-care
      settings.

PMID- 22399018
TI  - Osteoarticular tuberculosis mimicking rheumatoid arthritis.
AB  - Tuberculosis (TB) remains a global burden despite extensive efforts to control
      it. TB arthritis commonly manifest as monoarthritis of weight-bearing joints. We
      report a rare presentation of osteoarticular TB involving multiple small joints
      of the hands, which mimicked rheumatoid arthritis (RA). Magnetic resonance
      imaging showed tenosynovitis. The patient was initially treated for seronegative
      RA but failed to respond. Subsequently, synovial biopsy led to the diagnosis.
      Antituberculosis treatment was given for 1 year.

PMID- 22399019
TI  - Depression does not affect the treatment outcome of CBT for panic and
      agoraphobia: results from a multicenter randomized trial.
AB  - BACKGROUND: Controversy surrounds the questions whether co-occurring depression
      has negative effects on cognitive-behavioral therapy (CBT) outcomes in patients
      with panic disorder (PD) and agoraphobia (AG) and whether treatment for PD and AG
      (PD/AG) also reduces depressive symptomatology. METHODS: Post-hoc analyses of
      randomized clinical trial data of 369 outpatients with primary PD/AG (DSM-IV-TR
      criteria) treated with a 12-session manualized CBT (n = 301) and a waitlist
      control group (n = 68). Patients with comorbid depression (DSM-IV-TR major
      depression, dysthymia, or both: 43.2% CBT, 42.7% controls) were compared to
      patients without depression regarding anxiety and depression outcomes (Clinical
      Global Impression Scale [CGI], Hamilton Anxiety Rating Scale [HAM-A], number of
      panic attacks, Mobility Inventory [MI], Panic and Agoraphobia Scale, Beck
      Depression Inventory) at post-treatment and follow-up (categorical). Further, the
      role of severity of depressive symptoms on anxiety/depression outcome measures
      was examined (dimensional). RESULTS: Comorbid depression did not have a
      significant overall effect on anxiety outcomes at post-treatment and follow-up,
      except for slightly diminished post-treatment effect sizes for clinician-rated
      CGI (p = 0.03) and HAM-A (p = 0.008) when adjusting for baseline anxiety
      severity. In the dimensional model, higher baseline depression scores were
      associated with lower effect sizes at post-treatment (except for MI), but not at
      follow-up (except for HAM-A). Depressive symptoms improved irrespective of the
      presence of depression. CONCLUSIONS: Exposure-based CBT for primary PD/AG
      effectively reduces anxiety and depressive symptoms, irrespective of comorbid
      depression or depressive symptomatology.

PMID- 22399020
TI  - Integrated genome-wide pathway association analysis with INTERSNP.
AB  - OBJECTIVES: Pathway association analysis (PAA) tests for an excess of moderately
      significant SNPs in genes from a common pathway. METHODS: We present a Monte
      Carlo simulation framework that allows to formulate the main ideas of existing
      PAA approaches using a self-contained rather than a competitive null hypothesis.
      A stand-alone implementation in INTERSNP makes time-consuming communication with
      standard GWAS software redundant. By additional parallelization with the OpenMP
      API, we achieve a reduction in running time for PAA by orders of magnitude,
      making a power simulation study for PAA feasible. Our approach properly accounts
      for linkage disequilibrium and is robust with respect to residual lambda
      inflation. RESULTS: We demonstrate that under simple, realistic disease models,
      PAA can actually strongly outperform the GWAS single-marker approach. PAA methods
      that make use of the strength of the SNP association (GenGen, Fisher's
      combination test), in general, perform better than ratio-based methods (ALIGATOR,
      SNP ratio), whereas the relative performance of gene-based scoring (ALIGATOR,
      GenGen) and pathway-based scoring (SNP ratio, Fisher's combination test) depends
      on the architecture of the assumed disease model. Finally, we present a new PAA
      score that models independent signals from the same gene in a regression
      framework and show that it is a reasonable compromise that combines the
      advantages of existing ideas.

PMID- 22399022
TI  - iPhones for eye surgeons.

PMID- 22399024
TI  - Identification from dorsal finger pattern: a new approach.
AB  - The dorsal aspect of the hand has been little studied for the purpose of
      identification and hence the present study was undertaken to explore the
      feasibility of considering the skin creases on the dorsal aspect of the proximal
      inter-phalangeal joints (dorsal finger pattern) as a criteria for personal
      identification. The study included 257 native Bengali subjects, 140 males and 117
      females from the city of Kolkata. The dorsal aspects of the fingers of both hands
      were photographed by a digital camera and the images were analysed on a computer
      using Microsoft Photoeditor. The skin creases over the proximal inter-phalangeal
      joints were studied in three segments - proximal, middle and distal. Thus a total
      of 257 * 10 * 3 = 7710 segments were studied to determine the dorsal finger
      patterns. Five basic types of stems were noted - horizontal, vertical, oblique,
      semi-lunar and mixed. Among these the horizontal stem was the most common at
      90.49%. Branching was of two types - body branching and terminal branching. Body
      branching was more common than the terminal type. Semi-lunar stem was the rarest
      type of stem comprising less than 1%. Accuracy of the technique for confirmation
      of identity was found to be 91.9%.

PMID- 22399025
TI  - Mesiodistal width of canines: a tool for sex determination.
AB  - Teeth, in the living as well as the dead, are the most useful objects in the
      field of forensic investigation. Their ability to survive in situations like mass
      disasters makes them important tools in victim identification. Though the
      morphology and structure is similar in both men and women, there are subtle
      differences. Variation in dental size can give a clue about differences between
      the sexes. Many authors have measured the crowns of teeth in both men and women
      and found certain variations. Canines, reported to survive air crash and
      hurricane disasters, are perhaps the most stable teeth in the oral cavity because
      of the labiolingual thickness of the crown and the root anchorage in the alveolar
      process of the jaws. Measurement of mesiodistal width of the mandibular and
      maxillary canines provides good evidence of sex identification due to dimorphism.

PMID- 22399026
TI  - Incidents in an adolescent forensic secure inpatient service.
AB  - There has been increased research in recent years on incidents within adolescent
      inpatient psychiatric units, although findings to date have been somewhat
      inconsistent. We analysed all reported incidents by 37 consecutively discharged
      patients from a mixed sex adolescent forensic hospital. Findings include a very
      high overall rate of incidents. A small number of female patients with emerging
      emotionally unstable personality disorder accounted for the majority of violent
      incidents and other incidents. Almost all the patients assaulted someone during
      their admission. Patients on civil sections of the Mental Health Act had just as
      many incidents as patients on forensic sections. The vast majority of assaults
      were on staff. Peak times for incidents were the end of each day when education
      sessions were timetabled and the beginning of the night shift.

PMID- 22399027
TI  - Estimation of dental age and its comparison with chronological age: accuracy of
      two radiographic methods.
AB  - INTRODUCTION: Accurate age data are always necessary in medicine and dentistry,
      and are also important to assess maturity and estimate age in a number of
      disciplines, such as forensic odontology, paediatric and preventive dentistry,
      orthodontics, etc. AIM: This investigation determines the accuracy of dental age
      estimation and its comparison with chronological age by two methods: Demirjian's
      and Willems'. MATERIALS AND METHODS: Tooth development was assessed in seven left
      mandibular teeth from 215 orthopantomograms (OPGs) belonging to healthy children
      aged 6-15 years selected by convenience sampling, from patients of the Sudha
      Rustagi College of Dental Sciences & Research, Faridabad, and were staged
      according to Demirjian's and Willems' scales. The statistical analysis was
      performed using the unpaired 't'-test and the correlation was analysed using Karl
      Pearson's correlation coefficients test. RESULTS: Overall, Willems' method was
      found to be more accurate with a mean age overestimation of 0.36 years (SD =
      0.38) in boys and 0.24 years (SD = 0.36) in girls, and Demirjian's method
      produced a mean overestimation of 0.66 years (SD = 0.41) in boys and 0.56 years
      (SD = 0.43) in girls, respectively. Also, correlation between the two methods
      revealed a high coefficient value, 0.9947 for boys and 0.9944 for girls (P <
      0.05). CONCLUSION: Despite the favourable result of Willems' method in comparison
      with Demirjian's method, this study demonstrated a high correlation coefficient
      between both chronological and obtained dental age, thus confirming their
      potential applicability in clinical practice and forensic dentistry.

PMID- 22399028
TI  - Do psychiatric inpatients know their rights? A re-audit on information given to
      inpatients at a London mental health trust about their rights and admission to
      hospital.
AB  - This re-audit assessed whether wards at South West London and St Georges' mental
      health trust (SWLSTG) met agreed standards regarding informing inpatients about
      their legal status in hospital and rights, following an initial audit in 2009.
      Three general adult wards were re-audited, and other general and specialist wards
      (addictions, eating disorders, deaf services and obsessive compulsive disorder)
      were added. One hundred and five people (61 informal, 44 detained under the
      Mental Health Act 1983, revised 2007) on 10 wards were interviewed using an
      agreed proforma. The re-audit of wards A-C showed improvement: 81.3% of informal
      inpatients were aware of their legal status, versus 54.2% in 2009 (P = 0.101).
      Including new wards D-K, 90.2% knew their status (P = 0.0002). Of the informal
      patients, 65.6% knew they could refuse treatment (P = 0.0184) (on wards A-C,
      68.8%, P = 0.105) versus 37.5% in 2009. Despite some improvement, the patient
      experience of informal admission or detention in hospital still sometimes crosses
      legal boundaries. This audit highlights the need to improve awareness of patient
      rights and demonstrated how local presentation of audit improves practice.

PMID- 22399029
TI  - Homicide by direct snake bite: a case of contract killing.
AB  - It has been estimated that five million snake bite cases occur worldwide every
      year, causing about 100,000 deaths. Snake bite is exclusively accidental in
      nature. Suicide by snake bite is very rare and homicidal snake bite is not
      reported. In the present case, a contract killer was hired, who used a poisonous
      snake to kill an elderly couple by way of direct snake bite. We believe this to
      be the first case reported where a snake was directly used for the murder of two
      victims through a contract killer.

PMID- 22399030
TI  - A state of reversed hypoxic encephalopathy following attempted suicidal hanging:
      a boon.
AB  - Normal functional condition of the brain is achieved by maintaining the normal
      structure and normal function of brain parenchyma. Reduced blood supply and
      deficiency of available oxygen alter brain perfusion which causes hypoxia or
      anoxia, and, depending on the severity, alters brain functions temporarily or
      permanently. This can occur in cases of hanging. Some degree of permanent
      cerebral damage is inevitable if hypoxic-ischaemia lasts beyond 3-5 minutes. Here
      we present a case report in which even though the patient was hanged for more
      than five minutes until the formation of a ligature mark and exhibited cyanosis,
      unconsciousness and seizures, the outcome was favourable with prompt and early
      intervention. Recovery was complete such that there were no residual signs and
      symptoms of reduced brain perfusion.

PMID- 22399035
TI  - Expert witnesses in the coronial system.

PMID- 22399031
TI  - Iatrogenic perforation of a pulmonary angiomatoid lesion: histopathological study
      and review of the literature.
AB  - Percutaneous tube thoracostomy (PTT) remains the most widely performed procedure
      to manage blunt or penetrating chest traumas. This life-saving manoeuvre can be
      frequently associated with complications. We present the case of a 76-year-old
      man, admitted to a peripheral hospital after a car accident and treated by PTT,
      who died shortly after the withdrawal of the chest tube. At autopsy, the victim
      was found to be affected by an extensive haemothorax resulting from the
      perforation of a subpleural angiomatoid lesion. The histopathological
      characteristics and the pathogenesis of the iatrogenic injury involving the
      vascular abnormality, along with its causal role in determining the fatal
      haemothorax, are critically discussed under both clinical and forensic points of
      view.

PMID- 22399037
TI  - New legislation in China balancing the rights of both doctors and patients.

PMID- 22399039
TI  - The comparison of the effect of corticosteroids and platelet-rich plasma (PRP)
      for the treatment of plantar fasciitis.
AB  - INTRODUCTION: In this study, the results of local injection of platelet-rich
      plasma (PRP) and corticosteroids in the treatment of plantar fasciitis were
      compared. PATIENTS AND METHODS: Sixty patients who were diagnosed as plantar
      fasciitis and treated conservatively for at least 3 months and had no response to
      conservative treatment modalities were involved in this study. The first 30
      consecutive patients were treated by local injection of 2 mL of 40 mg
      Methylprednisolone with 2 mL of 2% prilocaine (metilprednizalone) and the second
      30 patients were treated by injecting 3 mL PRP after 2 mL of 2% prilocaine
      injection. Patients were evaluated according to the modified criteria of the
      Roles and Maudsley scores and visual analog scale before injection and 3 weeks
      and 6 months following injection. RESULTS: The mean VAS heel pain scores measured
      6 months after treatment were 3.4 in steroid group and 3.93 in PRP group, and the
      scores in both groups were significantly lower when compared with pretreatment
      levels (6.2 in steroid group and 7.33 in PRP group). There was no significant
      difference between steroid and PRP groups in visual analog scale scores and
      modified criteria of the Roles and Maudsley scores measured at 3 weeks and 6
      months (P > 0.05). CONCLUSION: Our results revealed that both methods were
      effective and successful in treating plantar fasciitis. When the potential
      complication of corticosteroid treatment was taken into consideration, PRP
      injection seems to be safer and at least having same effectivity in the treatment
      of plantar fasciitis.

PMID- 22399038
TI  - Noninvasive stratum corneum sampling and electron microscopical examination of
      skin barrier integrity: pilot study with a topical glycerin formulation for
      atopic dermatitis.
AB  - INTRODUCTION: Therapy of atopic dermatitis encloses use of medicated and
      nonmedicated preparations. Results of clinical and biophysical procedures
      indirectly describe the condition of the impaired skin barrier (SB). Direct
      evaluation of SB integrity is only possible by electron microscopical
      visualization, e.g. intercellular lipid lamellae (ICLL) organization of the
      stratum corneum. METHOD: SB integrity was measured by morphometric analysis of
      ICLL in healthy and atopic skin and after a 15-day treatment (plus 7-day follow
      up) of atopic skin with a glycerin preparation. RESULTS: Significant treatment
      effect was shown by the restoration of the ICLL. CONCLUSIONS: The study reveals
      that morphometric analysis of ICLL organization is suitable to differentiate
      between healthy and diseased skin and to semiquantitatively determine the effect
      of a nonmedicated glycerin formulation. LIMITATION: Small treatment cohort.

PMID- 22399040
TI  - Normal sagittal of the anterior cruciate ligament can be reproduced using
      accessory anteromedial portal technique: a magnetic resonance imaging study.
AB  - INTRODUCTION: Over time, the need for anatomic anterior cruciate ligament (ACL)
      to restore normal kinematics and postoperative function of the knee has been
      accepted. The purpose of this study was to compare the sagittal alignment of
      reconstructed ACL, which is performed between transtibial (TT) technique and
      accessory anteromedial (AAM) portal technique and between the reconstructed and
      the normal side in the same patient. In addition, we used the head of a metallic
      femoral interference screw as a reference to measure the femoral tunnel position.
      PATIENTS AND METHODS: This was a retrospective study with 15 patients in each
      group: accessory anteromedial portal technique (n = 15), TT technique (n = 15)
      and contralateral normal side of each technique group (15 knees per technique).
      Magnetic resonance images of the ACL sagittal angle and radiographs of the
      coronal screw angle were used for comparing the two groups. The paired t test was
      used to compare operated and contralateral normal knee and independent t test was
      used to compare the TT and the AAM groups. RESULTS: The sagittal angle of ACL of
      AAM technique (51.6 +/- 3.3 degrees ) was not different from the normal side
      (50.8 +/- 2.1 degrees ) (P = 0.270), however that of the TT technique (59.9 +/-
      5.7 degrees ) was significantly different from the normal side (50.9 +/- 2.4
      degrees ) (P < 0.001). The sagittal angle of AAM technique was significantly
      lower than that of the TT technique (P < 0.001). The coronal angle of the screw
      to axis of the femur in AAM technique (51.7 +/- 3.8 degrees ) was more horizontal
      than that of the TT technique (24.4 +/- 8.9 degrees ) (P < 0.001). The center of
      the screw head of the AAM technique was 30.7 +/- 3.1 % of the Blumensaat line and
      39.2 +/- 5.2 % of the condylar height. CONCLUSION: The anatomic sagittal angle of
      ACL can be achieved using the AAM technique compared with the TT technique. In
      addition, the angle of the screw in coronal plane was more horizontal using the
      AAM technique than with use of the TT technique. LEVEL OF EVIDENCE: Level III,
      diagnostic study.

PMID- 22399041
TI  - The 9th Palliative Care Congress.

PMID- 22399042
TI  - Touching lives': making a difference through matchmaking  in an HIV clinic.

PMID- 22399043
TI  - Provision of information about malignant spinal cord compression: perceptions of
      patients and staff.
AB  - BACKGROUND: Various guidelines have highlighted the importance of patients being
      given information on malignant spinal cord compression (MSCC), both when
      diagnosed with the condition and as a tool to aid early detection. AIM: To
      determine patient and staff views on the provision of MSCC information to
      patients with a diagnosis of or considered to be at high risk of developing MSCC.
      METHODS: Patients with MSCC admitted to a large regional cancer centre in
      Scotland over a 6-month period were interviewed. Staff were also surveyed using
      similar questions. RESULTS: Fifty-six patients and fifty staff were recruited.
      Only 4% of staff reported giving any written information about MSCC to patients
      with a confirmed diagnosis, although 20% of patients said they received it and
      77% wanted it. A total of 54% of staff reported gaving prophylactic information
      about MSCC to patients, although the majority of the patients (86%) said they
      would have wanted this information. Patients generally did not access additional
      information about MSCC and were dependent on the limited amount provided by the
      health-care team. CONCLUSION: Health professionals need to ensure that patients
      get the information they want, which will allow them to recognize MSCC symptoms
      early for improved treatment outcomes or to better adapt to a diagnosis.

PMID- 22399044
TI  - A hypnotherapy intervention for the treatment of anxiety in patients with cancer
      receiving palliative care.
AB  - This pilot study aimed to assess the benefits of hypnotherapy in the management
      of anxiety and other symptoms, including depression and sleep disturbance, in
      palliative care patients with cancer. Eleven hospice patients received four
      sessions of hypnotherapy and completed the Hospital Anxiety and Depression Scale,
      the Edmonton Symptom Assessment System, and the Verran and Snyder-Halpern Scale
      at set time points. Wrist actigraphy also provided an objective assessment of
      sleep quality. After the second hypnotherapy session there was a statistically
      significant reduction in mean anxiety and symptom severity, but not in depression
      or sleep disturbance. After the fourth session there was a statistically
      significant reduction in all four patient-reported measures but not in
      actigraphy. These results offer evidence that hypnotherapy can reduce anxiety in
      palliative care patients, as well as improving sleep and the severity of
      psychological and physical symptoms. Further studies are needed to explore
      whether the observed benefits were a direct result of the hypnotherapy and how
      the intervention could most benefit this patient population.

PMID- 22399045
TI  - Knowledge and perceived competence among nurses caring for the dying in long-term
      care homes.
AB  - BACKGROUND: The quality of care provided to dying long-term care (LTC) residents
      is often inadequate, which may be due to the lack of formal training that LTC
      staff receive in palliative care (PC). The present cross-sectional study assessed
      PC knowledge and self-efficacy in ability to provide PC in a sample of registered
      nurses working in LTC homes. METHOD: A survey was conducted in four LTC homes in
      October 2009 to June 2010. Nursing staff knowledge of PC was evaluated using the
      Palliative Care Quiz for Nurses (PCQN). The Self-Efficacy in End-of-Life Care
      Survey (S-EOLC) was used to measure nursing staff confidence in their ability to
      provide PC. FINDINGS: Close to 60% of the nursing staff participated (69 of 119).
      The participants did not score highly on the PCQN: the average correct score
      ranged from 52.50% to 63.41% across the homes. There were no significant
      differences between the homes for the mean number of correct responses on the
      PCQN (P=0.329) or mean scores for the three S-EOLC subscales. Rank ordering of
      the percentage of correct PCQN answers by item and LTC home demonstrated that
      similar misconceptions were held across homes. CONCLUSION: Despite their
      confidence in PC practice, the participants' PC knowledge gap reveals a need for
      PC training for staff working in LTC homes. The PC education and training
      provided should both include a gerontological perspective and address the
      expertise and knowledge already held by staff.

PMID- 22399046
TI  - A multimodal, interdisciplinary programme for the management  of cachexia and
      fatigue.
AB  - Fatigue and cachexia are common symptoms of advanced disease that have a
      significant impact on quality of life for palliative care clients. Management of
      cachexia and fatigue is often overlooked, but growing understanding of the
      multidimensional nature of fatigue and muscle wasting has led to interest in a
      model of care based on multimodal therapy that has been successfully implemented
      in specialized multidisciplinary hospital-based clinics in the
      oncology/palliative care setting. This article reports on an innovative
      incorporation of features of this model into a client-centred, interdisciplinary
      programme that aims to manage the effects of cachexia and fatigue and to improve
      quality of life for palliative care clients in their home setting. This Cachexia
      and Fatigue Management Programme (CFMP) involves the use of an anti-inflammatory
      agent, high protein intake, and an individually tailored resistance exercise
      regimen to counteract muscle wasting and fatigue. The article provides an
      overview of the role of multimodal therapies in the management of cachexia and
      fatigue before moving on to discuss the development of the CFMP, its features,
      and potential benefits for palliative care clients, caregivers, and health
      services.

PMID- 22399047
TI  - Identifying and treating depression at the end of life and among the bereaved.
AB  - Depression is a common psychological condition among patients at the end of life,
      and it can also affect a patient's family both before and after their loved one's
      death. It is estimated that around 25% of palliative care patients are diagnosed
      with depression during their illness, and that a majority experience depressive
      symptoms. If left unrecognized and untreated this may lead to more severe illness
      symptoms, poor communication with family members and, ultimately, reduced quality
      of life and a poor prognosis. Early assessment and management using appropriate
      tools as a guide are essential for enabling early treatment so that patients can
      be comfortable and meet unfulfilled goals during their end-of-life care.
      Palliative care staff play an essential part in recognizing and treating
      depression in patients, and by focusing on those at risk they can help to reduce
      the number who will go on to develop the condition. This article provides an
      overview of the nature of the problem in palliative care patients and bereaved
      families, looking at how targeted monitoring and intervention can help to
      alleviate the burden in the former and how support can benefit the latter.

PMID- 22399051
TI  - A highly selective sulfur-free iridium(III)-complex-based phosphorescent
      chemidosimeter for detection of mercury(II) ions.
AB  - A neutral phosphorescent coordination compound bearing a benzimidazole ligand,
      Ir(pbi)(2)(acac) (Hpbi = 1,2-diphenyl-1H-benzo[d]imidazole; Hacac =
      acetylacetone), is demonstrated to be the first example of a sulfur-free iridium
      complex for the detection of Hg(2+) cations with high selectivity and
      sensitivity. Ir(pbi)(2)(acac) shows a multisignaling response towards mercury(II)
      ions through UV-vis absorption, phosphorescence and electrochemistry
      measurements. Upon addition of Hg(2+) ions, solutions of this complex change from
      yellow to colorless, which could be observed easily by the naked eye, while its
      phosphorescence turns from bright green (lambda(PLmax) = 520 nm) into faint
      skyblue (lambda(PLmax) = 476 nm), and the detection limit is calculated to be 2.4
      * 10(-7) mol L(-1). (1)H NMR spectroscopic titration as well as ESI-MS results
      indicate that the decomposition of Ir(pbi)(2)(acac) in the presence of Hg(2+)
      through rupture of Ir-O bonds is responsible for the significant variations in
      both optical and electrochemical signals.

PMID- 22399050
TI  - Modification of caffeine effects on the affect-modulated startle by neuropeptide
      S receptor gene variation.
AB  - RATIONALE/OBJECTIVES: Both the neuropeptide S (NPS) system and antagonism at the
      adenosine A2A receptor (e.g., by caffeine) were found to play a crucial role in
      the mediation of arousal and anxiety/panic in animal and human studies.
      Furthermore, a complex interaction of the neuropeptide S and the adenosinergic
      system has been suggested with administration of the adenosine A2A receptor
      antagonist caffeine downregulating NPS levels (Lage et al., 2006) and attenuating
      the stimulatory effects of NPS in rodents (Boeck et al., 2010). METHODS: Thus, in
      the present study, the impact of the functional neuropeptide S receptor (NPSR)
      A/T (Asn(107)Ile; rs324981) variant on affect-modulated (neutral, unpleasant, and
      pleasant IAPS pictures) startle response depending on the administration of 300
      mg caffeine citrate was investigated in a sample of 124 (m = 58, f = 66) healthy
      probands using a double-blind, placebo-controlled design. RESULTS: ANOVA revealed
      a significant interaction between NPSR genotype, challenge condition, and picture
      valence. Comparing startle magnitudes upon stimulation with neutral or emotional
      pictures between the placebo and caffeine condition, in AA/AT non-risk genotype
      carriers no significant difference was discerned, while TT risk genotype carriers
      showed a significantly increased startle magnitude in response to neutral stimuli
      (p = .02) and a significantly decreased startle magnitude in response to
      unpleasant stimuli (p = .02) in the caffeine condition as compared to the placebo
      condition. CONCLUSIONS: In summary, the present findings - extending previous
      evidence from rodent studies - for the first time provide support for a complex,
      non-linear interaction of the neuropeptide S and adenosinergic systems affecting
      the affect-modulated startle response as an intermediate phenotype of anxiety in
      humans.

PMID- 22399052
TI  - An in silico model of enterocytic glutamine to citrulline conversion pathway.
AB  - Enterocyte is one of the main sites of amino acids metabolism and particularly of
      the citrulline biosynthesis. Working at the cellular scale and applying ordinary
      differential equations (ODEs) formalism, we have built a mathematical model of
      the enterocytic glutamine to citrulline conversion in the fasting state. This
      model enables us to test different physiopathological scenarios of enzyme
      activity loss. Results from two different approaches were compared: a standard
      approach (KA) based on the Michaelis-Menten assumptions and an association
      dissociation approach (VH) based on the kinetic mass action law. For both
      approaches, ODEs system was numerically solved using MathematicaTM. In both
      cases, the model correctly predicts the physiological plasma citrulline steady
      state, but the two approaches present clear differences for metabolites of
      enzymes having a complex mechanism, challenging the validity of the KA approach
      in such cases. When physiopathological scenarios of enzyme activity loss are
      simulated, both approaches predict a very sharp transition from the physiological
      citrulline plasma level to the lack of its production: the concentration profiles
      of these simulations show a clear threshold of which characteristics vary with
      the involved enzyme. Moreover, amongst all enzymes included in the model, the
      ornithine aminotransferase (OAT) shows the highest sensitivity in the system
      whatever the approach used. This model points out the limits of the Michaelis
      Menten approach to model complex enzyme mechanisms. It highlights the key role of
      OAT in the studied citrulline synthesis pathway and also suggests an order of
      magnitude about the optimal ratio of enzyme concentrations in this pathway.

PMID- 22399053
TI  - Is sexual concordance related to awareness of physiological states?
AB  - Sexual concordance refers to the degree to which two aspects of human sexual
      arousal (genital response and self-reported sexual arousal) correspond with each
      other. Researchers have consistently reported a sex difference in sexual
      concordance: The relationship between genital responses and reported feelings of
      sexual arousal in men is positive and large, whereas the relationship in women is
      positive but much smaller than that seen in men. The study of interoception-
      people's awareness of their physiological states--reveals a similar sex
      difference: Men are more aware of a variety of (non-genital) responses (e.g.,
      heart rate) than women in the laboratory. The purpose of the current study was to
      investigate whether the sex difference in sexual concordance was related to a
      broader sex difference in interoception. Twenty men and 20 women were presented
      with twelve 90 s sexual and non-sexual film clips while their genital responses,
      heart rate, and respiration rate were measured. Participants also estimated their
      physiological responses. As expected, men were significantly more sexually
      concordant than women. Men were also significantly more aware of their heart
      rate, but there was no significant sex difference in respiration rate awareness.
      Sexual concordance was not significantly correlated with either heart rate or
      respiration rate awareness. The results suggest that the sex difference in sexual
      concordance may be a unique phenomenon, separate from general awareness of
      physiological states.

PMID- 22399054
TI  - Sexual behavior in an intensive care unit.

PMID- 22399056
TI  - NHC-catalysed diastereoselective synthesis of multifunctionalised piperidines via
      cascade reaction of enals with azalactones.
AB  - NHC-catalysed azalactone ring-opening and piperidine ring-closing cascade with
      alpha,beta-unsaturated aldehydes (enals) in a one-pot operation is reported. The
      present reaction cascade offers a convenient method for a highly
      diastereoselective synthesis of multifunctionalised piperidines in excellent
      yields under mild conditions.

PMID- 22399055
TI  - Further data concerning Blanchard's (2011) "Fertility in the mothers of firstborn
      homosexual and heterosexual men".

PMID- 22399058
TI  - [Psychiatrists under National Socialism. Biographies of perpetrators].

PMID- 22399057
TI  - Inhibition of stromal CXCR4 impairs development of lung metastases.
AB  - Compelling evidence has emerged in recent years indicating that stromal cells
      play a critical role in disease progression. CXCR4 is a G-protein-coupled
      receptor with a major role in lymphocyte homing. Its ligand, CXCL12, is a highly
      efficient chemotactic factor for T cells, monocytes, pre-B cells, dendritic cells
      and myeloid bone marrow-derived cells (BMDCs). In addition, the CXCR4-CXCL12 axis
      plays a central role in tumor growth and metastasis. To evaluate the effect of
      genetic CXCR4 reduction on metastasis development, murine melanoma B16 cells were
      injected into the tail vein of C57BL/6 CXCR4(+/+) and CXCR4(+/-) mice in the
      presence of the CXCR4 inhibitor, Plerixafor (previously named AMD3100). Although
      lung metastases developed in wild-type CXCR4(+/+) and heterozygote CXCR4(+/-)
      mice, nodules were significantly smaller in the latter. CXCR4 pharmacological
      inhibition by Plerixafor further reduced lung metastases in CXCR4(+/-) mice,
      preserving the pulmonary architecture (4.18 +/- 1.38 mm(2) vs. 1.11 +/- 0.60
      mm(2), p = 0.038). A reduction in LY6G-positive myeloid/granulocytic cells and in
      p38 MAPK activation was detected in lungs from CXCR4(+/-) mice compared to
      CXCR4(+/+) mice [LY6G-positive myeloid CXCR4(+/-) vs. CXCR4(+/+) (p = 0.0004);
      CXCR4(+/+) vs. CXCR4(+/+) Plerixafor-treated (p = 0.0031)] suggesting that CXCR4
      reduction on myeloid-derived cells reduced their recruitment to the lung,
      consequently impairing lung metastases. Our findings argue in favor of a specific
      role of CXCR4 expressed in stromal cells that condition the pro-tumor
      microenvironment. In this scenario, CXCR4 antagonists will target neoplastic
      cells as well as the pro-tumor stromal microenvironment.

PMID- 22399059
TI  - [Paul Nitsche: psychiatric reformer and main protagonist of Nazi euthanasia].
AB  - The professional career of Paul Nitsche reflects the contradictory path taken by
      a German institutional psychiatrist who was a leader in the field at the time.
      During the Weimar Republic he advocated improving the institutional system based
      on principles of psychiatric reform, but was already receptive to concepts of
      racial hygiene. Shortly after the National Socialists seized power, Nitsche was
      already an influential proponent and participant in eugenic measures in Saxony
      and actively involved in implementing the "Law for the Prevention of Genetically
      Diseased Offspring." He increasingly appraised the value of a patient according
      to the person's economic performance. It was also Nitsche's opinion that the
      consequence of this extreme rationalization of human life was to exterminate
      "life unworthy of life." As a T4 appointed head assessor he decided in the last
      instance whether thousands of people would live or die. As the Medical Director
      of the T4 program, he was later directly responsible for continuing the massacre
      as "decentralized euthanasia." At the euthanasia trial in Dresden he was
      condemned to death and executed in 1948.

PMID- 22399060
TI  - [Murdering the sick in the name of progress? The Heidelberg psychiatrist Carl
      Schneider as a brain researcher and "therapeutic idealist"].
AB  - The biography of the Heidelberg Professor of Psychiatry Carl Schneider (1891
      1946) represents a combination of a quest for psychiatric reform, pronounced
      interest in brain research, and commitment to the first systematic extermination
      of a minority during the Nazi era, the murder of psychiatric patients. Guided by
      a biological concept that included the individual and his environment and thus
      interpreting the interactive and social sphere from a purely biological
      viewpoint, Schneider considered cure and extermination as two sides of the same
      coin. Psychiatric patients should receive intensive "biological" therapy, but if
      they were incurable and could not be integrated into society, they lost their
      reason for existence also in the biological sense. This can be illustrated by
      Schneider's research department in Heidelberg (1943/1944) where 52 children and
      adolescents were subjected to an extensive diagnostic program. Twenty of these
      children were murdered in the name of research at the Eichberg psychiatric
      asylum.

PMID- 22399061
TI  - [Friedrich Mauz: T4 assessor and military psychiatrist].
AB  - Friedrich Mauz is one of the medical perpetrators of the second tier whose
      biography is difficult to comprehend. Autobiographies from three different
      political systems exist - Weimar Republic, the Third Reich, and postwar Germany
      in which he constantly reinvented himself. While after 1933 he suddenly
      emphasized his participation in the civil war turmoil during the early period of
      the Weimar Republic and his patriotism, he then depicted himself after 1945 as an
      apolitical person characterized by Wurttemberg pietism who inwardly rejected the
      Nazi State but had found himself prepared to accept "all sorts of humiliating
      concessions." He claimed that he had always remained true to his scientific code
      of conduct and had distanced himself from psychiatric genetics. In point of fact,
      Mauz was among those exonerated in the denazification trial in 1946 and was able
      to pursue his career in the Federal Republic of Germany. However, if the sources
      are read against the grain, a different picture emerges. Mauz's career stalled in
      the 1930s, not because he had been politically offensive, but because his
      scientific work was flimsy and considered lacking originality, particularly since
      he had chosen constitution research and psychotherapy as his main fields of
      interest, which were overshadowed by research in genetic psychiatry in the 1930s.
      Mauz tendered his services to the Nazi policy of genetic health, served as a
      medical assessor in proceedings based on the "Law for the Prevention of
      Genetically Diseased Offspring," permitted himself to be recruited for the T4
      program as a medical expert, even participated in the deliberations on a future
      "Law on Euthanasia," and as a consulting psychiatrist for the German Armed Forces
      contributed to military medicine.

PMID- 22399062
TI  - [Friedrich Panse: well established in all systems. Psychiatrist in the Weimar
      Republic, in the Third Reich, and in the Federal Republic of Germany].
AB  - The psychiatrist Friedrich Panse (1899-1973) was a T4 assessor during the Nazi
      era who sent mentally disabled and mentally ill people to their deaths. In the
      German Armed Forces he used higher galvanic currents to cure "war neurotics" and
      expose "malingerers." As a National Socialist he was a committed teacher of
      racial hygiene. Nonetheless, after the end of the Nazi regime many supporters
      quickly surfaced who were prepared to exonerate Panse. Panse himself was not
      among those who indignantly repudiated the accusation of any contact with the
      Nazi Party. He did not deny that he had openly embraced the Nazi measures for
      preserving the genetic integrity of the populace, but he did let it be known that
      he had suffered incredibly under the heavy burden. The State Government of North
      Rhine-Westphalia refused to allow Panse to continue in his capacity as an
      extraordinary professor. Panse successfully contested this decision at the State
      Administrative Court in Dusseldorf. He became the Director of the Institution in
      Dusseldorf-Grafenberg, the Psychiatric Clinic in Dusseldorf, a member of the
      German Council of Medical Advisors for questions regarding care for war victims
      of the German Federal Ministry of Labor, and President of the German Society for
      Psychiatry and Neurology.

PMID- 22399065
TI  - First-trimester screening for spontaneous preterm delivery with maternal
      characteristics and cervical length.
AB  - OBJECTIVE: It was the aim of this study to examine the potential value of
      cervical length at 11-13 weeks' gestation in the prediction of spontaneous
      preterm delivery. METHODS: This was a screening study for spontaneous preterm
      delivery in singleton pregnancies from cervical length measured by transvaginal
      ultrasound at 11-13 weeks' gestation. The performance of screening for preterm
      delivery by cervical length alone and with maternal characteristics was
      estimated. RESULTS: In the 9,974 pregnancies included in the study, spontaneous
      delivery before 34 weeks occurred in 104 (1.0%) cases. Multivariate regression
      analysis in the term delivery group demonstrated that for the log(10) cervical
      length, significant independent contributions were provided by fetal crown-rump
      length, maternal height, age, racial origin and parity. The median cervical
      length multiple of the median (MoM), corrected for maternal characteristics, was
      significantly lower in the preterm (0.892 MoM, 95% CI 0.829-0.945) than in the
      term delivery group (0.994 MoM, 95% CI 0.919-1.082; p < 0.0001). In screening by
      a combination of maternal characteristics and cervical length, the estimated
      detection rate of preterm delivery was 54.8% (95% CI 44.7-64.6), at a false
      positive rate of 10%. CONCLUSIONS: Effective first-trimester screening for
      spontaneous early preterm delivery can be provided by a combination of maternal
      characteristics and cervical length.

PMID- 22399066
TI  - A data types profile suitable for use with ISO EN 13606.
AB  - ISO EN 13606 is a five part International Standard specifying how Electronic
      Healthcare Record (EHR) information should be communicated between different EHR
      systems and repositories. Part 1 of the standard defines an information model for
      representing the EHR information itself, including the representation of types of
      data value. A later International Standard, ISO 21090:2010, defines a
      comprehensive set of models for data types needed by all health IT systems. This
      latter standard is vast, and duplicates some of the functions already handled by
      ISO EN 13606 part 1. A profile (sub-set) of ISO 21090 would therefore be expected
      to provide EHR system vendors with a more specially tailored set of data types to
      implement and avoid the risk of providing more than one modelling option for
      representing the information properties. This paper describes the process and
      design decisions made for developing a data types profile for EHR
      interoperability.

PMID- 22399067
TI  - An authentication scheme to healthcare security under wireless sensor networks.
AB  - In recent years, Taiwan has been seeing an extension of the average life
      expectancy and a drop in overall fertility rate, initiating our country into an
      aged society. Due to this phenomenon, how to provide the elderly and patients
      with chronic diseases a suitable healthcare environment has become a critical
      issue presently. Therefore, we propose a new scheme that integrates healthcare
      services with wireless sensor technology in which sensor nodes are employed to
      measure patients' vital signs. Data collected from these sensor nodes are then
      transmitted to mobile devices of the medical staff and system administrator,
      promptly enabling them to understand the patients' condition in real time, which
      will significantly improve patients' healthcare quality. As per the personal data
      protection act, patients' vital signs can only be accessed by authorized medical
      staff. In order to protect patients', the system administrator will verify the
      medical staff's identity through the mobile device using a smart card and
      password mechanism. Accordingly, only the verified medical staff can obtain
      patients' vital signs data such as their blood pressure, pulsation, and body
      temperature, etc.. Besides, the scheme includes a time-bounded characteristic
      that allows the verified staff access to data without having to have to re
      authenticate and re-login into the system within a set period of time.
      Consequently, the time-bounded property also increases the work efficiency of the
      system administrator and user.

PMID- 22399068
TI  - Creating content modules for Chinese EHR documents and their trial implementation
      in Wuwei City.
AB  - Numerous and diverse paper-based health record documents are currently used in
      China, which are not only different from each other but are also inconsistent
      with national regulations. If these documents are made to be structured and
      electronically available, the health records information can be processed by
      computers to promote a shareable electronic health record (EHR) across
      organizations. As such, this work was intended to develop a set of content
      modules to be employed as reusable building blocks for converting the paper-based
      health records to structured EHR documents. Therefore, in this study, we
      developed 77 content modules based on the documents of national specifications
      and implemented them to Wuwei City as a trial. According to the EHR requirements
      of Wuwei, we added two new content modules in addition to the 77 existing content
      modules. We then successfully established an EHR system based on the new content
      modules in combination with the original content modules. This paper could
      contribute to the construction of structured Chinese EHR documents and provide
      some experiences as a reference for building EHR systems.

PMID- 22399070
TI  - Identification of novel components of NAD-utilizing metabolic pathways and
      prediction of their biochemical functions.
AB  - Nicotinamide adenine dinucleotide (NAD) is a ubiquitous cofactor participating in
      numerous redox reactions. It is also a substrate for regulatory modifications of
      proteins and nucleic acids via the addition of ADP-ribose moieties or removal of
      acyl groups by transfer to ADP-ribose. In this study, we use in-depth sequence,
      structure and genomic context analysis to uncover new enzymes and substrate
      binding proteins in NAD-utilizing metabolic and macromolecular modification
      systems. We predict that Escherichia coli YbiA and related families of domains
      from diverse bacteria, eukaryotes, large DNA viruses and single strand RNA
      viruses are previously unrecognized components of NAD-utilizing pathways that
      probably operate on ADP-ribose derivatives. Using contextual analysis we show
      that some of these proteins potentially act in RNA repair, where NAD is used to
      remove 2'-3' cyclic phosphodiester linkages. Likewise, we predict that another
      family of YbiA-related enzymes is likely to comprise a novel NAD-dependent ADP
      ribosylation system for proteins, in conjunction with a previously unrecognized
      ADP-ribosyltransferase. A similar ADP-ribosyltransferase is also coupled with
      MACRO or ADP-ribosylglycohydrolase domain proteins in other related systems,
      suggesting that all these novel systems are likely to comprise pairs of ADP
      ribosylation and ribosylglycohydrolase enzymes analogous to the DraG-DraT system,
      and a novel group of bacterial polymorphic toxins. We present evidence that some
      of these coupled ADP-ribosyltransferases/ribosylglycohydrolases are likely to
      regulate certain restriction modification enzymes in bacteria. The ADP
      ribosyltransferases found in these, the bacterial polymorphic toxin and host
      directed toxin systems of bacteria such as Waddlia also throw light on the
      evolution of this fold and the origin of eukaryotic polyADP-ribosyltransferases
      and NEURL4-like ARTs, which might be involved in centrosomal assembly. We also
      infer a novel biosynthetic pathway that might be involved in the synthesis of a
      nicotinate-derived compound in conjunction with an asparagine synthetase and
      AMPylating peptide ligase. We use the data derived from this analysis to
      understand the origin and early evolutionary trajectories of key NAD-utilizing
      enzymes and present targets for future biochemical investigations.

PMID- 22399069
TI  - Uromodulin and alpha(1)-antitrypsin urinary peptide analysis to differentiate
      glomerular kidney diseases.
AB  - BACKGROUND/AIMS: Glomerular kidney disease (GKD) is suspected in patients based
      on proteinuria, but its diagnosis relies primarily on renal biopsy. We used urine
      peptide profiling as a noninvasive means to link GKD-associated changes to each
      glomerular entity. METHODS: Urinary peptide profiles of 60 biopsy-proven
      glomerular patients and 14 controls were analyzed by combining magnetic bead
      peptide enrichment, MALDI-TOF MS analysis, and ClinProTools v2.0 to select
      differential peptides. Tentative identification of the differential peptides was
      carried out by HPLC-MS/MS. RESULTS: The HPLC-MS/MS results suggest that
      uromodulin (UMOD; m/z: 1682, 1898 and 1913) and alpha(1)-antitrypsin (A1AT; m/z:
      1945, 2392 and 2505) are differentially expressed urinary peptides that
      distinguish between GKD patients and healthy subjects. Low UMOD and high A1AT
      peptide abundance was observed in 80-92% of patients with GKD. Proliferative
      forms of GKD were distinguished from nonproliferative forms, based on a
      combination of UMOD and A1AT peptides. Nonproliferative forms correlated with
      higher A1AT peptide levels - focal segmental glomerulosclerosis was linked more
      closely to high levels of the m/z 1945 peptide than minimal change disease.
      CONCLUSION: We describe a workflow - urinary peptide profiling coupled with
      histological findings - that can be used to distinguish GKD accurately and
      noninvasively, particularly its nonproliferative forms.

PMID- 22399071
TI  - Design and synthesis of a "click" high-mannose oligosaccharide mimic emulating
      Man8 binding affinity towards Con A.
AB  - A dendritic "click" mannooligomer mimicking the high-mannose oligosaccharide
      Man(8) has been designed by replacing some of the inner mannopyranosyl subunits
      with triazole moieties; evaluation of its binding affinity towards the mannose
      specific lectin concanavalin A revealed striking similarities between the "click"
      mimic and the natural Man(8).

PMID- 22399072
TI  - External validation of a D-dimer age-adjusted cut-off for the exclusion of
      pulmonary embolism.

PMID- 22399073
TI  - Association between the valine/leucine247 polymorphism of beta2-glycoprotein I
      and susceptibility to anti-phospholipid syndrome: a meta-analysis.
AB  - OBJECTIVE: The objective of this paper is to explore whether the
      valine/leucine(247) (Val/Leu(247)) polymorphism of beta(2)-glycoprotein I
      (beta(2)GPI) confers susceptibility to anti-phospholipid syndrome (APS) and
      thrombosis and predicts positivity for anti-beta(2)GPI antibodies. METHODS: A
      meta-analysis was conducted on the associations between the beta(2)GPI
      Val/Leu(247) polymorphism and susceptibility to APS and thrombosis and positivity
      for anti-beta(2)GPI. RESULTS: A total of 1507 patients with APS and 1450 controls
      in 12 comparative studies were included in this meta-analysis. Meta-analysis of
      the beta(2)GPI Val/Leu(247) polymorphism showed significant associations between
      the beta(2)GPI Val allele and APS, thrombosis, and anti-beta(2)GPI positivity
      (odds ratio (OR) 1.316, 95% confidence interval (CI) 1.068-1.621, p = 0.010; OR
      1.908, 95% CI 1.195-3.046, p = 0.007; OR 1.630, 95% CI 1.018-2.609, p = 0.042,
      respectively). A direct comparison between anti-beta(2)GPI-positive and -negative
      patients revealed that the frequency of the Val allele was significantly higher
      in anti-beta(2)GPI-positive patents (OR 1.514, 95% CI 1.017-1.253, p = 0.041).
      Furthermore, a direct comparison between thrombosis-positive and -negative
      patients also indicated that the Val/Val + Val/Leu and the Val/Val vs. Leu/Leu
      genotypes of the beta(2)GPI polymorphism were significantly elevated in patients
      with thrombosis (OR 2.817, 95% CI 1.200-6.610, p = 0.017; OR 3.312, 95% CI 1.338
      8.200, p = 0.010, respectively). CONCLUSION: This meta-analysis shows that the
      beta(2)GPI Val/Leu(247) polymorphism is associated with susceptibility to APS and
      thrombosis and with anti-beta(2)GPI positivity.

PMID- 22399074
TI  - Eculizumab as rescue therapy for atypical hemolytic uremic syndrome with normal
      platelet count.
AB  - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) in childhood is a rare
      disease with frequent progression to end-stage renal disease and a high
      recurrence after kidney transplantation. Eculizumab, a humanized monoclonal
      antibody that binds to complement protein C5, may be beneficial in the treatment
      of aHUS. CASE-DIAGNOSIS/TREATMENT: A 6-year-old girl developed aHUS with only
      slightly elevated C3d (4.4%), no mutations in complement factors, and no
      antibodies against factor H. Plasma exchange treatment was successful initially,
      until aHUS recurred. After reinitiating plasma exchange, normalization of the
      platelet count and improvement of hemolysis occurred, but renal function
      worsened. Renal function then improved dramatically promptly after the switch to
      eculizumab. CONCLUSIONS: This case demonstrates that platelet count is not always
      a reliable marker for improvement of aHUS and that eculizumab can prevent
      dialysis in plasma-resistant aHUS patients.

PMID- 22399075
TI  - Race-specific relationship of birth weight and renal function among healthy young
      children.
AB  - BACKGROUND: Low birth weight is associated with diminished renal function.
      However, despite African Americans being at increased risk of low birth weight
      and chronic kidney disease, little is known about the association between birth
      weight and renal function in diverse groups. We examined racial differences in
      the relationship of birth weight and renal function among healthy young children.
      METHODS: Birth weight and serum creatinine data were available on 152 children
      (61.8% African American; 47.4% female) from a birth cohort. Estimated glomerular
      filtration rate (eGFR) was calculated using the bedside Schwartz equation and
      gender- and gestational-age-adjusted birth weight Z-scores using the US
      population as a reference. Race-specific linear regression models were fit to
      estimate the association between birth weight Z-score and eGFR. RESULTS: Mean age
      was 1.5  +/-  1.3 years at first eGFR measurement. African Americans had lower
      eGFR than non-African Americans (median eGFR = 82 vs. 95 ml/min per 1.73 m(2); p
      = 0.06). Birth weight was significantly and positively associated with eGFR among
      African American (p = 0.012) but not non-African American children (p = 0.33).
      CONCLUSIONS: We provide, for the first time, evidence suggesting that birth
      weight is associated with renal function in African American children. Future
      work is needed to determine if prenatal programming helps explain racial
      disparities in adult health.

PMID- 22399077
TI  - Visible biofilms - a controversial issue!

PMID- 22399076
TI  - The effects of psychotherapy on psychological well-being and diurnal cortisol
      patterns in breast cancer survivors.
AB  - BACKGROUND: Neuroendocrine dysregulation influenced by psychosocial stress is
      related to breast cancer recurrence. Very few studies examine the impacts of
      psychotherapy on diurnal cortisol patterns among breast cancer survivors.
      METHODS: Forty-eight breast cancer patients who completed active cancer treatment
      were randomly assigned to receive either 8 weekly body-mind-spirit (BMS) group
      therapy sessions or 1 educational (EDU) session. Self-report measures included
      the Beck Depression Inventory-II (BDI-II), and the Meaning in Life questionnaire
      (MLQ) including two subscales: MLQ-Presence and MLQ-Search. Salivary cortisol
      levels were collected by the subjects in their homes at the time of awakening, 30
      and 45 min after awakening, and at 12.00, 17.00, and 21.00 h. Measurement time
      points include baseline, the 2nd month (completion of BMS therapy), the 5th
      month, and the 8th month. RESULTS: There were no significant differences in BDI
      II scores (p>0.05) and MLQ-Presence scores (p >0.05) between BMS and EDU groups
      at baseline or across the three follow-ups. Nevertheless, greater MLQ-Search
      scores were found in the BMS group compared to the EDU group during the 5th month
      of follow-up (p <0.01). The higher level of cortisol at 21.00 h (p < 0.01) and a
      flatter diurnal cortisol pattern were more likely to occur in EDU than in BMS
      participants (p < 0.05) at the 8th month of follow-up. CONCLUSION: BMS group
      therapy likely contributed to enhancing an active search for meaning in life
      toward more opportunities for personal growth and to maintaining stable cortisol
      responses to everyday life stress for breast cancer survivors.

PMID- 22399078
TI  - Potential implications of biofilm  in chronic wounds: a case series.
AB  - Bacterial biofilm is increasingly suspected as being a significant barrier to
      wound healing. Bacteria predominantly attach to surfaces in their natural
      habitats and form biofilm; in this state they adapt to, and tolerate, the
      hostilities in their surrounding environment. The purpose of this clinical
      observational study was to consider chronic wound biofilm in relation to other
      factors that are implicated in wound recalcitrance, such as peripheral arterial
      disease, wound infection, osteomyelitis and moisture imbalance. Based on our
      clinical observations, it is possible that links exist between wound biofilm and
      other underlying pathophysiological factors, and that biofilm may also provide
      clues to the involvement of such factors. Recognising and managing these factors
      collectively may be important in addressing recalcitrance and facilitating wound
      progression.

PMID- 22399079
TI  - The challenges of managing a complex stoma with NPWT.
AB  - This paper reports the clinical experience of a 71-year-old female with resection
      of the colon, who subsequently developed postoperative complications. A colostomy
      was carried out; necrosis of the colostomy edges and stoma retraction complicated
      optimal stoma appliance placement. It was possible to treat the resulting cavity
      with negative pressure wound therapy (NPWT) by isolating the stoma and treating
      the peristomal wound area. The wound was treated with NPWT for 30 days; at day
      20, the patient was discharged to home to continue with NPWT for a further 10
      days by community nurses, with regular follow-up visits in the outpatient clinic.
      The patient improved steadily and achieved complete closure of the wound.

PMID- 22399080
TI  - A systematic review of the ASEPSIS scoring system used in non-cardiac-related
      surgery.
AB  - OBJECTIVE: To assess the validity, reliability and sensitivity of the ASEPSIS
      scoring system, used to assess non-cardiac related surgery for surgical wound
      infection. METHOD: Five studies were included in this review. One study discussed
      the development of the ASEPSIS scoring system; two studies were on its
      reliability, one study on the sensitivity and the final compared the ASEPSIS
      scoring system against other surgical wound infection criteria and definitions.
      Due to variation in study designs, the findings were summarised and presented in
      a narrative format. RESULTS: Validity and reliability were not established in
      assessing non-cardiac surgical sites. Sensitivity level was reported for non
      cardiac surgical sites, but its reliability level declined as the severity of
      infection worsened. CONCLUSION: This review revealed that there are limited
      choices of scoring systems to assess different surgical sites for surgical wound
      infection. Currently, only the ASEPSIS scoring system is available, but it is not
      validated for use with non-sternal wounds. Therefore, it should be used
      cautiously when assessing non-cardiac surgical wound infection.

PMID- 22399082
TI  - Wound biofilms-are they visible?

PMID- 22399081
TI  - Efficacy and safety of hyaluronic acid in treatment of leg ulcers:  a double
      blind RCT.
AB  - OBJECTIVE: To investigate the efficacy and safety of hyaluronic acid in the local
      treatment of leg ulcers of venous or mixed aetiology, compared with a neutral
      vehicle. METHOD: A 60-day double-blind, randomised, multicentre, controlled
      superiority trial. The primary endpoint was the percentage wound size reduction
      after 45 days of treatment. Secondary endpoints included pain intensity, rate of
      complete ulcer healing, and aspect of the wound (percentage of necrotic,
      fibrinous or granulation tissue) and of the peri-ulcer skin. RESULTS: A total of
      101 patients were randomised and analysed in the intention-to-treat (ITT)
      population (50 in the hyaluronic acid; 51 in the control group). Seventy-five
      patients were considered in the per protocol (PP) population (38 vs 37,
      respectively). At day 45, the percentage of ulcer surface reduction was
      significantly greater in the hyaluronic acid treatment group (39 +/- 6%) compared
      with the neutral vehicle (control) group (5 +/- 9%) (p=0.002). A similar result
      was obtained at day 15, day 30 and day 60. From day 0 to day 45, pain intensity
      (VA S) decreased by mean 9.8 +/- 3.5mm in the hyaluronic acid group, but slightly
      increased by 0.8 +/- 3.2mm in the control group (p=0.029). Burden of pain, as
      estimated by the area under the curve of daily pain (from day 0 to day 60), was
      significantly lower in the hyaluronic acid group (121.9 +/- 20.7mm2) than in the
      control group (207.4 +/- 32.9mm2; p=0.028). Other secondary endpoints (rate of
      complete healing, characteristics of the wound and peri-ulcer skin) were not
      significantly different between the two groups. Treatments were well tolerated
      and adverse events were comparable between the two groups in terms of their
      frequency, relationship to treatment and severity. CONCLUSION: Hyaluronic acid
      cream was significantly more effective than the neutral vehicle in the local
      treatment of leg ulcers of venous or mixed aetiology, in terms of wound size
      reduction and reducing the burden of pain, with a good safety profile.

PMID- 22399083
TI  - Management of diabetic foot ulcers with a TLC-NOSF wound dressing.
AB  - OBJECTIVE: To evaluate the efficacy, tolerance and acceptability of UrgoStart
      Contact (Laboratoires Urgo), a new wound dressing impregnated with NOSF, as an
      MMP regulator in the management of neuropathic diabetic foot ulcers. METHOD: A
      multicentre, pilot, prospective, non-controlled open-label clinical trial. Adult
      patients with type 1 or 2 diabetes mellitus, who had a grade 1A (Texas
      classification), uninfected, neuropathic foot ulcer, 1-15cm2 in size and of 1-20
      months' duration (mean 6.7 +/- 5.2 months) were included in the study. The
      primary endpoint was the relative reduction of the wound surface area (%) at the
      end of the study. Secondary endpoints included rate of complete healing, and
      tolerability and acceptability of the dressing. The wound dressing was changed
      regularly at the investigator's discretion, in accordance with the wound status
      and exudate level. Patients were followed up every 2 weeks for a 12-week period.
      At each visit, patients underwent clinical assessments, and ulcer surface area
      was measured by planimetry and photographs. RESULTS: Thirty-four diabetic
      patients with a neuropathic foot ulcer were included but only 33 cases were
      analysed, as data were completely lost for one patient. At baseline, mean surface
      area was 2.7+/-2.4cm2. At the 12-week follow-up, the median surface area
      reduction was 82.7% (mean reduction 62.7 +/- 49.9%) and in 10 of the 33 analysed
      patients (30%) the wound was healed. Only two of the seven documented local
      adverse events were deemed to be dressing related. According to the nursing
      staff, acceptability was considered very satisfactory, particularly in term of
      conformability and ease of use. CONCLUSION: This pilot study indicates that use
      of the new UrgoStart Contact dressing, combined with offloading and
      debridement,may help promote the healing process of the neuropathic diabetic foot
      ulcers, and was well tolerated and accepted.

PMID- 22399084
TI  - The effect of different doses of an arginine-containing supplement on the healing
      of pressure ulcers.
AB  - OBJECTIVE: To investigate if a lower dose of arginine in the form of an oral
      nutritional supplement can show similar benefit in the healing rate of pressure
      ulcers compared with the current evidence for 9g of arginine. METHOD: Twenty
      three inpatients with category II, III or IV pressure ulcers were randomised to
      receive daily, for 3 weeks, the standard hospital diet plus 4.5 or 9g arginine in
      the form of a commercial supplement. Pressure ulcer size and severity was
      measured weekly (by PUSH tool; pressure ulcer scale for healing; 0= completely
      healed, 17= greatest severity). Nutritional status was determined by Subjective
      Global Assessment. RESULTS: There were no significant differences in patients'
      age, gender, BMI, haemoglobin levels, albumin levels and diagnosis of diabetes
      between treatment groups. There was a significant decrease in pressure ulcer
      severity over time (p < 0.001), with no evidence of a difference in healing rate
      between the two arginine dosages (p=0.991). Based on expected healing time,
      patients in both treatment groups were estimated to achieve an almost 2-fold
      improvement compared with the historical control group. Patients categorised as
      malnourished showed clinically significant impaired healing rates compared with
      well nourished patients (p=0.057), although this was unaffected by arginine
      dosage (p=0.727). CONCLUSION: Similar clinical benefits in healing of pressure
      ulcers can be achieved with a lower dosage of arginine, which can translate into
      improved concordance and significant cost-savings for both the health-care
      facilities and for patients.

PMID- 22399086
TI  - Perfusion IMP-SPECT shows reversible abnormalities in GABA(B) receptor antibody
      associated encephalitis with normal MRI.
AB  - A new subtype of autoimmune encephalitis associated with antibodies against
      GABA(B) receptor was recently identified. Although immune-mediated functional
      abnormalities are suggested for the pathogenesis, functional brain imaging such
      as perfusion SPECT has not been documented. A 62-year-old woman with anti-GABA(B)
      receptor associated encephalitis underwent (123)I-IMP SPECT in the beginning and
      after methylprednisolone pulse therapy. Three-dimensional stereotactic surface
      projection analysis was used to evaluate the cortical distribution of perfusion
      abnormality. The patient presented with clinical features of subacute limbic
      encephalitis. Antibodies to GABA(B) receptor were identified in her serum and
      cerebrospinal fluid (CSF), but no tumor was detected. Despite normal magnetic
      resonance imaging (MRI) findings, the first SPECT revealed hypoperfusion of the
      frontal, parietal and medial temporal lobes, as well as thalamus, and cerebellum.
      These areas are known to contain high levels of GABA(B) receptors. In contrast,
      the SPECT revealed hyperperfusion in the motor strip and left temporal lobe,
      which are areas related to some of the patient's symptoms, including seizures,
      orolingual dyskinesia, and Wernicke aphasia. After treatment with pulses of
      methylprednisolone, the neuropsychiatric symptoms resolved and the SPECT findings
      showed substantial improvement in most of these regions. In conclusion, the
      findings suggest that immunotherapy improved the cortical dysfunction mediated by
      GABA(B) receptor antibodies.

PMID- 22399085
TI  - Pilot data on telmisartan short-term effects on glucose metabolism in the
      olfactory tract in Alzheimer's disease.
AB  - The possible effect of antihypertensive therapy on Alzheimer's disease (AD) has
      been studied, and angiotensin II receptor blockers (ARBs) have been suggested to
      exert an effect on cognitive decline. The purpose of this study is to clarify the
      functional effects of telmisartan, a long-acting ARB, on AD brain using
      prospective longitudinal (18)F-fluorodeoxyglucose positron emission tomography
      (FDG-PET) studies. For this purpose, brain glucose metabolism of four
      hypertensive patients with AD was examined with FDG-PET before and after
      administration of telmisartan. Studied subjects underwent three FDG-PET studies
      at intervals of 12 weeks. Antihypertensive treatment except for telmisartan was
      started after the first FDG-PET and continued for 24 weeks. Then 40-80 mg of
      telmisartan was added after the second FDG-PET and continued for 12 weeks.Glucose
      metabolism was significantly decreased during the first 12 weeks without
      telmisartan use at an area (-10, 21, -22, x, y, z; Z = 3.56) caudal to the left
      rectal gyrus and the olfactory sulcus corresponding to the left olfactory tract.
      In contrast, the introduction of telmisartan during the following 12 weeks
      preserved glucose metabolism at areas (5, 19, -20, x, y, z; Z = 3.09; 6, 19, -22,
      x, y, z; Z = 2.88) caudal to the bilateral rectal gyri and olfactory sulci
      corresponding to the bilateral olfactory tracts. No areas showed decreased
      glucose metabolism after the introduction of telmisartan. In AD, amyloid-beta
      deposition is observed in the anterior olfactory nucleus (AON) of the olfactory
      tract. Glucose metabolism in AON may be progressively decreased and preserved by
      telmisartan.

PMID- 22399088
TI  - Neuroprotective effects of Tacrolimus (FK-506) and Cyclosporin (CsA) in oxidative
      injury.
AB  - The detrimental effects of hypoxic damage to central nervous system lead to
      energy depletion, free radical formation, lipid peroxidation (LPO), and increased
      calcium. We hypothesized that in vitro tacrolimus (FK-506) and cyclosporine A
      (CsA) could be protective against hypoxic damage in spinal cord. Dorsal columns
      were isolated from the spinal cord of adult rats and injured by exposure to
      hypoxic condition for 1 h, and treated with FK-506 (0.1 MUM) and CsA (0.1 MUM).
      After injury, reperfusion was carried out for 2 h. Tissues were collected,
      processed for biochemical assays, and 2,3,5-triphenyltetrazolium chloride (TTC)
      staining. Spinal cord hypoxia caused a significant decrease (P < 0.001) in
      mitochondrial ATP (30.64%) and tissue reduced glutathione (GSH) (60.14%) content.
      Conversely, a significant increase (P < 0.001) in tissue LPO level (57.77%) and
      myeloperoxidase (MPO) activity (461.24%) was observed in hypoxic group.
      Mitochondrial swelling was also significantly increased in hypoxic group (90.0%).
      Treatment with either FK-506 or CsA showed that significant neuroprotective
      effects (P < 0.05-0.01) were measured in various parameters in hypoxic groups. FK
      506 and CsA treatment showed increase in ATP by 11.19% and 16.14% while GSH
      content increased by 66.46% and 77.32%, respectively. Conversely, LPO content
      decreased by 18.97% and 24.06% and MPO level by 42.86% and 18.66% after FK-506
      and CsA treatment. Calcium uptake was also decreased in mitochondria as exhibited
      by the increase in absorbance by 11.19% after FK-506 treatment. TTC staining also
      showed increased viability after FK-506 and CsA treatment. In conclusion, present
      study demonstrates the neuroprotective effect of FK-506 and CsA treatment against
      spinal cord hypoxia induced damage is mediated via their antioxidant actions.

PMID- 22399087
TI  - The cell adhesion molecule L1 regulates the expression of choline
      acetyltransferase and the development of septal cholinergic neurons.
AB  - Mutations in the L1 gene cause severe brain malformations and mental retardation.
      We investigated the potential roles of L1 in the regulation of choline
      acetyltransferase (ChAT) and in the development of septal cholinergic neurons,
      which are known to project to the hippocampus and play key roles in cognitive
      functions. Using stereological approaches, we detected significantly fewer ChAT
      positive cholinergic neurons in the medial septum and vertical limb of the
      diagonal band of Broca (MS/VDB) of 2-week-old L1-deficient mice compared to wild
      type littermates (1644 +/- 137 vs. 2051 +/- 165, P = 0.038). ChAT protein levels
      in the septum were 53% lower in 2-week-old L1-deficient mice compared to wild
      type littermates. ChAT activity in the septum was significantly reduced in L1
      deficient mice compared to wild-type littermates at 1 (34%) and 2 (40%) weeks of
      age. In vitro, increasing doses of L1-Fc induced ChAT activity in septal neurons
      with a significant linear trend (*P = 0.0065). At 4 weeks of age in the septum
      and at all time points investigated in the caudate-putamen (CPu), the number of
      ChAT-positive neurons and the levels of ChAT activity were not statistically
      different between L1-deficient mice and wild-type littermates. The total number
      of cells positive for the neuronal nuclear antigen (NeuN) in the MS/VDB and CPu
      was not statistically different in L1-deficient mice compared to wild-type
      littermates, and comparable expression of the cell cycle marker Ki67 was
      observed. Our results indicate that L1 is required for the timely maturation of
      septal cholinergic neurons and that L1 promotes the expression and activity of
      ChAT in septal neurons.

PMID- 22399089
TI  - White matter maturation of normal human fetal brain. An in vivo diffusion tensor
      tractography study.
AB  - We demonstrate for the first time the ability to determine in vivo and in utero
      the transitions between the main stages of white matter (WM) maturation in normal
      human fetuses using magnetic resonance diffusion tensor imaging (DTI)
      tractography. Biophysical characteristics of water motion are used as an indirect
      probe to evaluate progression of the tissue matrix organization in cortico-spinal
      tracts (CSTs), optic radiations (OR), and corpus callosum (CC) in 17 normal human
      fetuses explored between 23 and 38 weeks of gestation (GW) and selected strictly
      on minimal motion artifacts. Nonlinear polynomial (third order) curve fittings of
      normalized longitudinal and radial water diffusivities (Z-scores) as a function
      of age identify three different phases of maturation with specific dynamics for
      each WM bundle type. These phases may correspond to distinct cellular events such
      as axonal organization, myelination gliosis, and myelination, previously reported
      by other groups on post-mortem fetuses using immunostaining methods. According to
      the DTI parameter dynamics, we suggest that myelination (phase 3) appears early
      in the CSTs, followed by the OR and by the CC, respectively. DTI tractography
      provides access to a better understanding of fetal WM maturation.

PMID- 22399091
TI  - Genetic association of the Phosphoinositide-3 kinase in schizophrenia and bipolar
      disorder and interaction with a BDNF gene polymorphism.
AB  - Phosphoinositide-3-kinase, class III (PIK3C3) is a member of the phosphoinosite-3
      kinases family, involved in cell signaling, membrane trafficking, and
      neurodevelopment. Previous studies have indeed shown an association between
      PIK3C3 gene variants and both bipolar disorder (BD) and schizophrenia (SZ). Brain
      derived neurotrophic factor (BDNF) is a neurodevelopmental factor, which can
      regulate the PI3K signaling pathway. Associations have been reported between BDNF
      gene polymorphisms and affective and psychotic disorders. The aim of the present
      study was to replicate an association between PIK3C3 and BDNF gene variants in SZ
      and BD and a putative epistasis between the two genes. Patients meeting the DSM
      IV criteria of BD and SZ were included in this study (98 BD and 79 SZ) as well as
      158 healthy controls. Blood DNA was extracted and genotyping was performed either
      by the polymerase chain reaction (PCR) technique followed by enzymatic digestion
      or by the high-resolution melt (HRM) method. Genotype and haplotype association
      was assessed with the UNPHASED statistical program.The results showed one nominal
      association with BD (P < 0.02) and two risk haplotypes in both SZ (P < 0.001) and
      BP (P < 0.0005), which survived multiple testing correction. A modest interaction
      between a BDNF variant and PI3KC3 polymorphism was observed (P < 0.04).These
      preliminary results confirm the genetic association of PI3K gene variants with
      both SZ and BD, and support the hypothesis that SZ and BD share a genetic
      background.

PMID- 22399090
TI  - Genetically determined dopamine availability predicts disposition for depression.
AB  - Although prominent personality theories postulate orthogonality between traits of
      positive emotionality (PEM) and negative emotionality (NEM), empirical evidence
      often demonstrates the opposite indicating a negative relationship. Therefore, it
      is not surprising that dopaminergic (DA) gene loci have been related to traits of
      positive and of NEM. The present genetic association study investigates the
      influence of two functional DA gene polymorphisms on Sadness as defined by the
      Affective Neuroscience Personality Scales (ANPS) in healthy Caucasians (n =
      1041). We observed a significant interaction effect between the 10-repeat (10R)
      allele of the dopamine transporter (DAT1) gene and the methionine (Met) allele of
      the catechol-O-methyltransferase (COMT) Val158Met polymorphism (F((1,1018)) =
      11.11; P < 0.001). Carriers of the 9R/9R and the Val/Val genotype showed
      dramatically reduced Sadness scores in comparison to the other three genotype
      configurations. Both the 9R/9R and the Val/Val genotypes characterized by reduced
      transporter density and high dopamine catabolism, respectively, have been
      separately related to personality traits of PEM and externalizing behavior in the
      past. The present findings indicate that gene variations of the DA system
      previously associated with PEM are at the same time protective against high NEM
      and can therefore constitute a resilience factor against depression.

PMID- 22399092
TI  - Mixed handedness is associated with greater age-related decline in volumes of the
      hippocampus and amygdala: the PATH through life study.
AB  - Handedness has been found to be associated with structural and functional
      cerebral differences. Left handedness and mixed handedness also appear to be
      associated with an elevated risk of some developmental and immunological
      disorders that may contribute to pathological processes developing in ageing.
      Inconsistent reports show that left handedness may be more prevalent in early
      onset as well as late-onset Alzheimer's disease, but might also be associated
      with slower decline. Such inconsistencies may be due to handedness being usually
      modeled as a binary construct while substantial evidence suggests it to be a
      continuous trait. The aim of this study was to investigate the relationship
      between brain structures known to be implicated in pathological ageing and
      strength and direction of handedness. The association between handedness and
      hippocampal and amygdalar atrophy was investigated in 327 cognitively healthy
      older individuals. Handedness was measured with the Edinburgh Inventory. Two
      measures were computed from this index, one reflecting the direction (left =
      0/right = 1) and the other the degree of handedness (ranging from 0 to 1).
      Hippocampal and amygdalar volumes were manually traced on scans acquired 4 years
      apart. Regression analyses were used to assess the relationship between strength
      and direction of handedness and incident hippocampal and amygdalar atrophy.
      Analyses showed that strength but not direction of handedness was a significant
      predictor of hippocampal (Left: beta = 0.118, P = 0.013; Right: beta = 0.116, P =
      0.010) and amygdalar (Right: beta = 0.105, P = 0.040) atrophy. The present
      findings suggest that mixed but not left handedness is associated with greater
      hippocampal and amygdalar atrophy. This effect may be due to genetic,
      environmental, or behavioural differences that will need further investigation in
      future studies.

PMID- 22399093
TI  - Polymorphisms of GSTT1, GSTM1, and EPHX genotypes in patients with cryptogenic
      polyneuropathy: a case-control study.
AB  - The aim of this study was to analyze whether polymorphisms for the null alleles
      of Glutathione S-Transferase Mu-1 (GSTM1), Glutathione S-Transferase Theta-1
      (GSTT1), and a low-activity genetic variation of epoxide hydrolase exon three
      (EPHX*3) affect the risk of developing polyneuropathy. The enzymes of these genes
      are important in the metabolism of toxic compounds. Seventy-nine patients with
      cryptogenic polyneuropathy (equivalent to chronic idiopathic axonal neuropathy)
      and 398 controls were tested for the genetic polymorphism. Medical records were
      reviewed to collect data regarding clinical findings at diagnosis, and exposure
      data was collected via questionnaires. The odds ratios (ORs) for the null forms
      of GSTM1 and GSTT1 and the normal activity YY form of EPHX*3 were close to one
      except GSTT1, which reached 1.86. The highest risk of polyneuropathy was found in
      smokers with GSTT1 null, who had a 3.7 times increased risk. Interactions between
      genes were analyzed and confirmed the increased OR for GSTT1, which was strongest
      if the patients had the low-activity HH form of EPHX*3 (OR 2.37). Our hypothesis
      is that the GSTT1 null polymorphism may be related to an impaired metabolism of
      toxic substances that could lead to nerve damage in the peripheral nervous
      system.

PMID- 22399094
TI  - Residual vectors for Alzheimer disease diagnosis and prognostication.
AB  - Alzheimer disease (AD) is an increasingly prevalent neurodegenerative condition
      and a looming socioeconomic threat. A biomarker for the disease could make the
      process of diagnosis easier and more accurate, and accelerate drug discovery. The
      current work describes a method for scoring brain images that is inspired by
      fundamental principles from information retrieval (IR), a branch of computer
      science that includes the development of Internet search engines. For this
      research, a dataset of 254 baseline 18-F fluorodeoxyglucose positron emission
      tomography (FDG-PET) scans was obtained from the Alzheimer's Disease Neuroimaging
      Initiative (ADNI). For a given contrast, a subset of scans (nine of every 10) was
      used to compute a residual vector that typified the difference, at each voxel,
      between the two groups being contrasted. Scans that were not used for computing
      the residual vector (the remaining one of 10 scans) were then compared to the
      residual vector using a cosine similarity metric. This process was repeated
      sequentially, each time generating cosine similarity scores on 10% of the FDG-PET
      scans for each contrast. Statistical analysis revealed that the scores were
      significant predictors of functional decline as measured by the Functional
      Activities Questionnaire (FAQ). When logistic regression models that incorporated
      these scores were evaluated with leave-one-out cross-validation, cognitively
      normal controls were discerned from AD with sensitivity and specificity of 94.4%
      and 84.8%, respectively. Patients who converted from mild cognitive impairment
      (MCI) to AD were discerned from MCI nonconverters with sensitivity and
      specificity of 89.7% and 62.9%, respectively, when FAQ scores were brought into
      the model. Residual vectors are easy to compute and provide a simple method for
      scoring the similarity between an FDG-PET scan and sets of examples from a given
      diagnostic group. The method is readily generalizable to any imaging modality.
      Further interdisciplinary work between IR and clinical neuroscience is warranted.

PMID- 22399095
TI  - The stroke-prone spontaneously hypertensive rat: still a useful model for post
      GWAS genetic studies?
AB  - The stroke-prone spontaneously hypertensive rat (SHRSP) is a unique genetic model
      of severe hypertension and cerebral stroke. SHRSP, as well as the spontaneously
      hypertensive rat, the parental strain of SHRSP, has made a tremendous
      contribution to cardiovascular research. However, the genetic mechanisms
      underlying hypertension and stroke in these rats have not yet been clarified.
      Recent studies using whole-genome sequencing and comprehensive gene expression
      analyses combined with classical quantitative trait loci analyses provided
      several candidate genes, such as Ephx2, Gstm1 and Slc34a1, which still need
      further evidence to define their pathological roles. Currently, genome-wide
      association studies can directly identify candidate genes for hypertension in the
      human genome. Thus, genetic studies in SHRSP and other rat models must be focused
      on the pathogenetic roles of 'networks of interacting genes' in hypertension,
      instead of searching for individual candidate genes.

PMID- 22399096
TI  - Losartan/hydrochlorothiazide combination vs. high-dose losartan in patients with
      morning hypertension--a prospective, randomized, open-labeled, parallel-group,
      multicenter trial.
AB  - The treatment of morning hypertension has not been established. We compared the
      efficacy and safety of a losartan/hydrochlorothiazide (HCTZ) combination and high
      dose losartan in patients with morning hypertension. A prospective, randomized,
      open-labeled, parallel-group, multicenter trial enrolled 216 treated outpatients
      with morning hypertension evaluated by home blood pressure (BP) self-measurement.
      Patients were randomly assigned to receive a combination therapy of 50 mg
      losartan and 12.5 mg HCTZ (n=109) or a high-dose therapy with 100 mg losartan
      (n=107), each of which were administered once every morning. Primary efficacy end
      points were morning systolic BP (SBP) level and target BP achievement rate after
      3 months of treatment. At baseline, BP levels were similar between the two
      therapy groups. Morning SBP was reduced from 150.3+/-10.1 to 131.5+/-11.5 mm Hg
      by combination therapy (P<0.001) and from 151.0+/-9.3 to 142.5+/-13.6 mm Hg by
      high-dose therapy (P<0.001). The morning SBP reduction was greater in the
      combination therapy group than in the high-dose therapy group (P<0.001).
      Combination therapy decreased evening SBP from 141.6+/-13.3 to 125.3+/-13.1 mm Hg
      (P<0.001), and high-dose therapy decreased evening SBP from 138.9+/-9.9 to
      131.4+/-13.2 mm Hg (P<0.01). Although both therapies improved target BP
      achievement rates in the morning and evening (P<0.001 for both), combination
      therapy increased the achievement rates more than high-dose therapy (P<0.001 and
      P<0.05, respectively). In clinic measurements, combination therapy was superior
      to high-dose therapy in reducing SBP and improving the achievement rate (P<0.001
      and P<0.01, respectively). Combination therapy decreased urine albumin excretion
      (P<0.05) whereas high-dose therapy reduced serum uric acid. Both therapies
      indicated strong adherence and few adverse effects (P<0.001). In conclusion,
      losartan/HCTZ combination therapy was more effective for controlling morning
      hypertension and reducing urine albumin than high-dose losartan.

PMID- 22399097
TI  - Prehypertension should be considered a special blood pressure phase.

PMID- 22399099
TI  - Different profile of endothelial cell apoptosis in patients with Klinefelter's
      syndrome.
AB  - INTRODUCTION: The aim of this study was to evaluate the effects of testosterone
      (T) therapy on the sexual function of middle-aged patients with acquired pre
      pubertal hypergonadotropic hypogonadism (HrHy) and patients with Klinefelter
      syndrome (KS). PATIENTS AND METHODS: A selected series of 35 middle-aged
      hypogonadal patients, including those who had recently been observed during
      andrological counseling (extracted from our database) and had not yet begun
      hormonal treatment, was recruited for this evaluation. This series of patients
      included 20 patients with acquired prepubertal HrHy and 15 KS patients who were
      matched by age and body mass index. All patients underwent an andrological
      evaluation, which included the administration of the International Index of
      Erectile Function 5 (IIEF-5) questionnaire and the evaluation of penile echo
      color Doppler. In addition, by flow cytometry we evaluated the serum levels of
      apoptotic endothelial microparticles (EMPa) and the vitronectin receptor (VR) at
      baseline and 6 months after the onset of T therapy. RESULTS: After 6 months of T
      therapy, patients with HrHy demonstrated mean IIEF-5 scores and a peak systolic
      velocity that were significantly greater and a mean acceleration time that was
      significantly lower (p<0.05) than those of patients with KS (p<0.05). In
      addition, patients with HrHy showed mean EMPa values and VR serum concentrations
      that were significantly lower than those of patients with KS (p<0.05). KS
      patients showed significantly improved IIEF-5 scores and Doppler parameters
      (p<0.05) but not EMPa or VR serum concentrations following treatment. DISCUSSION:
      These results indicate that erectile dysfunction in KS can improve with T
      therapy, although this improvement is more profound in HrHy patients, and these
      results also suggest that T therapy does not improve the severity of endothelial
      cell apoptosis in KS patients.

PMID- 22399098
TI  - The effects of repeated delivery of angiotensin II AT(1) receptor antisense on
      distinct vasoactive systems in Ren-2 transgenic rats: young vs. adult animals.
AB  - Although Ren-2 transgenic rat (TGR) is defined as a model of angiotensin II
      dependent hypertension, we studied whether the renin-angiotensin system (RAS) is
      really the main contributor to blood pressure (BP) elevation in hetero- and
      homozygous TGRs. Moreover, we examined whether repeated antisense (AS) therapy
      against AT(1) receptors would have a similar effect on the BP and the
      contribution of the principle vasoconstrictor/vasodilator systems to BP
      regulation in young and adult TGRs. From the age of 30 (young) and 100 (adult)
      days, rats were injected with AS for 40 days in 10-day intervals. After 10 and 40
      days of AS therapy, the basal BP and acute BP responses to the sequential
      blockade of the RAS, sympathetic nervous (SNS) and nitric oxide systems were
      determined in conscious rats. The RAS system was the major system maintaining
      elevated BP in young homozygous animals, whereas there was an increasing
      contribution of the SNS in heterozygous TGR with age. The AS therapy in the young
      TGR had a transient BP-lowering effect that was associated with reduced cardiac
      hypertrophy; the AS therapy was most effective in young homozygous TGR, causing a
      substantial reduction of angiotensin-dependent vasoconstriction. In heterozygous
      rats, AS therapy at earlier stages was related to an inhibition of sympathetic
      vasoconstriction, whereas to RAS inhibition in established hypertension. In
      conclusion, repeated AS therapy had transient antihypertensive effects
      exclusively in young TGR. The contribution of the RAS to BP maintenance is highly
      important only in homozygous TGRs, whereas it is surpassed by SNS in heterozygous
      TGR.

PMID- 22399100
TI  - Photomagnetic studies on spin-crossover solid solutions containing two different
      metal complexes, [Fe(1-bpp)(2)](x)[M(terpy)2](1-x)[BF4]2 (M = Ru or Co).
AB  - The photomagnetic properties of two series of spin-crossover solid solutions,
      [Fe(1-bpp)(2)](x)[Ru(terpy)(2)](1-x)(BF(4))(2) and [Fe(1
      bpp)(2)](x)[Co(terpy)(2)](1-x)(BF(4))(2) (1-bpp = 2,6-bis[pyrazol-1-yl]pyridine),
      have been investigated. For all the materials, the evolution of the T(LIESST)
      value, the high-spin -> low-spin relaxation parameters and the LITH loops were
      thoroughly studied. Interestingly in the Fe:Co series, along the photo
      excitation, cobalt ions are concomitantly converted from low-spin to high-spin
      states with the iron centres, and also fully relax after light excitation.

PMID- 22399101
TI  - Effects of storage temperature on the change in size of Calliphora vicina larvae
      during preservation in 80% ethanol.
AB  - The size of immature blowflies is a common measure to estimate the minimum time
      between death and the discovery of a corpse, also known as the minimum post
      mortem interval. This paper investigates the effects of preservation, in 80%
      ethanol, on the length and weight of first instar, second instar, feeding third
      instar, and post-feeding third instar Calliphora vicina larvae, at three
      different storage temperatures. For each larval stage, the length of larvae was
      recorded after 0 h, 3 h, 6 h, 9 h, 12 h, 24 h, 72 h, 7 days, 14 days, 30 days, 91
      days, 182 days, 273 days, and 365 days of storage in 80% ethanol, at -25 degrees
      C, 6 degrees C and 24 degrees C. Storage temperature had no statistically
      significant effect on the change in larval length and weight for all larval
      stages, but larval length and weight were significantly affected by the duration
      of preservation for first, second, and feeding third instar larvae, but not for
      post-feeding larvae. Generally, first and second instar larvae reduced in size
      over time, while feeding third instar larvae increased slightly in size, and post
      feeding larvae did not change in size over time. The length of blowfly larvae
      preserved in 80% ethanol is not affected by constant storage temperatures between
      -25 degrees C and +24 degrees C, but we recommend that forensic entomologists
      should use the models provided to correct for changes in larval length that do
      become apparent over time.

PMID- 22399102
TI  - The application of traditional and geometric morphometric analyses for forensic
      quantification of sexual dimorphism: preliminary investigations in a Western
      Australian population.
AB  - A current limitation of forensic practice in Western Australia is a lack of
      contemporary population-specific standards for biological profiling; this
      directly relates to the unavailability of documented human skeletal collections.
      With rapidly advancing technology, however, it is now possible to acquire
      accurate skeletal measurements from 3D scans contained in medical databases. The
      purpose of the present study, therefore, is to explore the accuracy of using
      cranial form to predict sex in adult Australians. Both traditional and geometric
      morphometric methods are applied to data derived from 3D landmarks acquired in CT
      reconstructed crania. The sample comprises multi-detector computed tomography
      scans of 200 adult individuals; following 3D volume rendering, 46 anatomical
      landmarks are acquired using OsiriX (version 3.9). Centroid size and shape (first
      20 PCs of the Procrustes coordinates) and the inter-landmark (ILD) distances
      between all possible pairs of landmarks are then calculated. Sex classification
      effectiveness of the 3D multivariate descriptors of size and shape and selected
      ILD measurements are assessed and compared; robustness of findings is explored
      using resampling statistics. Cranial shape and size and the ILD measurements are
      sexually dimorphic and explain 3.2 to 54.3 % of sample variance; sex
      classification accuracy is 83.5-88.0 %. Sex estimation using 3D shape appears to
      have some advantages compared to approaches using size measurements. We have,
      however, identified a simple and biologically meaningful single non-traditional
      linear measurement (glabella-zygion) that classifies Western Australian
      individuals according to sex with a high degree of expected accuracy (87.5-88 %).

PMID- 22399104
TI  - Detection and characterization of traumatic scalp injuries for forensic
      evaluation using computed tomography.
AB  - The purpose of this prospective study was to evaluate the rate of detection and
      correct classification of traumatic soft tissue injuries of the head using
      clinical multislice computed tomography (MSCT) compared with an external forensic
      examination. Thirty-one patients with soft tissue injuries after head trauma and
      clinically indicated cerebral MSCT scan underwent an external forensic
      examination with documentation of the morphological appearance and the exact
      localization of scalp and facial injuries. MSCT data were evaluated by a
      radiologist blinded to the results of the external examination using axial images
      as well as multiplanar reconstruction tools. The results of the radiological and
      forensic report were compared and analyzed. The main finding was that clinical
      MSCT data of the head detected 55 % of all external lesions and diagnosed the
      correct morphological type of lesion in 30 %. All lacerations and 44 % of the
      hematomas were correctly identified in the radiological report, whereas the
      diagnosis of swellings and abrasions was difficult. MSCT showed a high
      specificity for all types of soft tissue lesions. Additionally, a substantial
      number of internal lesions such as fractures or intracerebral bleedings were
      revealed which were not detected in the external examination. The results
      demonstrate that the forensic-radiologic evaluation of clinical MSCT data has a
      good diagnostic performance and is a valuable method to retrospectively
      supplement external forensic examination in living crime victims. It also might
      to a certain extent-be used as the only source in cases where no forensic
      external examination has taken place within due time.

PMID- 22399103
TI  - Immunohistochemical analysis on cyclooxygenase-2 for wound age determination.
AB  - Immunohistochemical study combined with morphometry was carried out to examine
      the expression of cyclooxygenase-2 (COX-2) using 60 human skin wounds of
      different ages: group I, 0-4 h (n = 11); II, 8 h-2 days (n = 21); III, 3-9 days
      (n = 14); and IV, 12-21 days (n = 14). In wound specimens aged 2 h to 2 days,
      anti-myeloperoxidase-positive neutrophils observed at the wound site expressed
      immunopositive reaction to COX-2. In wound specimens of more than 3 days, CD68
      positive macrophages as well as neutrophils were positively immunostained with
      anti-COX-2. In group II, all 21 wound samples had COX-2-positive ratios of >40 %,
      and 15 out of them showed >50 %. In group III, only three wound samples with the
      postinfliction intervals of 3 days showed positive ratios of 40-50 % and the
      remaining 11 cases less than 40 %. In groups I and IV, all 25 wound specimens had
      COX-2-positive ratio of <40 %. With regard to the practical applicability with
      forensic safety, these observations suggested that a COX-2-positive ratio of >40
      % indicated a wound age of 8 h to 3 days. Moreover, COX-2-positive ratios,
      considerably exceeding a ratio of 50 %, indicate a wound age of 8 h to 2 days.
      Collectively, COX-2 would be a useful marker for the determination of early wound
      age.

PMID- 22399105
TI  - The impact of intermittent preventive treatment with sulfadoxine-pyrimethamine on
      the prevalence of malaria parasitaemia in pregnancy.
AB  - The Roll Back Malaria initiatives were introduced to ensure that 60% of pregnant
      women receive intermittent preventive anti-malarial treatment by the end of 2005
      in an attempt to halve the mortality from malaria by 2010. Our aim was to
      determine the prevalence of asymptomatic malaria parasitaemia in pregnant women
      on intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP)
      compared with a control group. This comparative study involved testing the
      peripheral blood of pregnant women on IPT with SP and a control group that did
      not receive SP for the malaria parasite upon registration and at 34 weeks
      gestational age. The levels of parasitaemia in the intervention group upon
      registration (4.9%) and at 34 weeks (63.9%) were not significantly different (P >
      0.05) from that of the control group (10%) and at 34 weeks gestation (68.3%). IPT
      with SP during pregnancy did not significantly reduce the prevalence of the
      malaria parasitaemia among the pregnant women in our environment.

PMID- 22399106
TI  - Massive ossification around the prosthesis after limb salvage treatment for
      osteosarcoma.

PMID- 22399107
TI  - Biomimetic sensing based on chemically induced assembly of a signaling DNA
      aptamer on a fluid bilayer membrane.
AB  - The adenosine aptamer was split into two halves and linked to a fluid liposome
      surface; addition of adenosine resulted in aptamer assembly, which did not occur
      if the split aptamer was attached to silica nanoparticles, demonstrating the
      feasibility of using aptamer probes to study diffusion within lipid membranes.

PMID- 22399108
TI  - [Controversies in urology].

PMID- 22399109
TI  - [Lymphadenectomy for bladder cancer: current status and controversies].
AB  - Pelvic lymph node dissection is an integral part of the radical cystectomy
      procedure for patients with muscle-invasive bladder cancer. The optimal extent of
      the lymphadenectomy (LND) and mainly the proximal template boundary remain
      controversial issues. In view of the existing mapping studies and retrospective
      analyses, extended LND up to the mid-upper third of the common iliac vessels
      appears to provide further prognostic and therapeutic benefit and therefore
      should be defined as standard LND. This applies for all procedures irrespective
      of the choice of surgical approach (open surgery, minimally invasive approach).
      In this context total lymph node count is not a quality criterion because nodal
      yield is overly influenced by the individual patient's anatomy, surgical
      technique, template applied and pathological work-up. Consecutively, considerable
      inter-institutional differences result, which render any comparison impossible.
      Lymph node density is thought to be a superior prognostic factor, but it is
      similarly influenced by the above-mentioned factors. Concerning molecular
      techniques to improve the sensitivity of postoperative nodal staging further
      research is necessary. The two ongoing prospective randomized trials will
      potentially help to further define the optimal LND template.

PMID- 22399110
TI  - [Therapy of male urinary incontinence: artificial sphincter versus male slings].
AB  - Different kinds of sling systems for the therapy of male urinary incontinence
      have been developed during the last decade. All systems work by compressing the
      male urethra. There are adjustable and non-adjustable systems. Implantation is
      mostly a minimally invasive procedure. On the other hand the well-established AMS
      800 hydraulic artificial sphincter has been available since 1972. Recently,
      another hydraulic artificial sphincter (FlowSecure) has become available
      providing a boost of occlusive pressure during stress. The aim of this review is
      to compare effectiveness and indications of the different techniques compared to
      the artificial sphincter.

PMID- 22399111
TI  - [Botulinum toxin versus sacral neuromodulation for idiopathic detrusor
      overactivity].
AB  - Idiopathic detrusor overactivity (motory urge) negatively affects the live of
      patients. Conservative treatment is not always effective and has multiple side
      effects. Sacral neuromodulation is a second line therapy for the treatment of
      idiopatic detrusor overactivity. Over the last decade, botulinum toxin injections
      have been increasingly used as alternative although there are only few randomized
      studies. Goal of this review is to compare efficiacy, safety and cost
      effectiveness of both methods.

PMID- 22399113
TI  - [Cancer-related fatigue. Psychosocial support].
AB  - Cancer-related fatigue is a subjective sensation of uncontrollable physical,
      emotional and/or cognitive tiredness and weakness, which occurs in the context of
      cancer or cancer-treatment. Cancer-related fatigue occurs at all stages of cancer
      treatment and can persist long after medical treatment. It profoundly affects
      patients' quality of life and limits their personal, social, and occupational
      lives. Cancer-related fatigue is also associated with significant levels of
      distress, and it imposes financial burdens by limiting a patient's ability to
      work. Current psychosocial interventions with strong or sufficient evidence
      include physical training, cognitive-behavioral training, relaxation techniques,
      psychoeducation and patient education. This article gives an overview of
      currently available psychosocial interventions and information on their
      implementation.

PMID- 22399118
TI  - Two missense mutations identified in venous thrombosis patients impair the
      inhibitory function of the protein Z dependent protease inhibitor.
AB  - Protein Z-dependent protease inhibitor (ZPI) is a plasma inhibitor of factor
      (F)Xa and FXIa. In an earlier study, five mutations were identified within the
      ZPI gene of venous thrombosis patients and healthy controls. Two of these were
      nonsense mutations and three were missense mutations in important regions of the
      protein. Here we report that two of these latter three mutations, F145L and
      Q384R, impair the inhibitory function of ZPI in vitro. Recombinant wild-type and
      mutant proteins were prepared; stability in response to thermal challenge was
      similar. Inhibition of FXa in the presence of the cofactor protein Z was reduced
      68-fold by the Q384R mutant; inhibition of FXIa by the F145L mutant was reduced
      two- to three-fold compared to the wild-type ZPI. An analysis of all five ZPI
      mutations was undertaken in a cohort of venous thrombosis patients (n=550)
      compared to healthy controls (n=600). Overall, there was a modest increase in
      incidence of these mutations in the thrombosis group (odds ratio 2.0, 1.05-3.7,
      p=0.044). However, in contrast to W324X (nonsense mutation), the Q384R missense
      mutation and R88X nonsense mutation were evenly distributed in patients and
      controls; F145L was rare. The final mutation (S143Y) was also rare and did not
      significantly alter ZPI function in laboratory studies. The F145L and
      particularly the Q384R mutation impaired the function of the coagulation
      inhibitor ZPI; however, there was no convincing association between these
      mutations and venous thrombosis risk. The functional role for ZPI in vivo has yet
      to be clarified.

PMID- 22399119
TI  - Systematic bottom-up approach for flavonoid derivative screening in plant
      material using liquid chromatography high-resolution mass spectrometry.
AB  - In this work, a systematic comprehensive screening procedure has been proposed
      for the detection of multiclass flavonoid derivatives by liquid chromatography
      high-resolution mass spectrometry (LC-HRMS). The procedure is based on the
      combined use of accurate mass measurements and in-source fragmentation obtained
      with a liquid chromatography time-of-flight mass spectrometry instrument. The
      method relies on automated screening of selected diagnostic ions based on an
      exact mass database. The included diagnostic ions represent theoretical
      combinations of aglycones and typical glycan part constituents of flavonoid
      derivatives (i.e., various saccharide units and acyl moieties). The proposed
      identification protocol is following a systematic evaluation of the obtained
      positive hits from the diagnostic ions database according to a "bottom-up"
      approach that is thoroughly discussed. The main benefit of the proposed bottom-up
      protocol resides in the fact that untargeted flavonoid derivatives can be
      detected and tentatively identified without the need for any preliminary
      knowledge on the sought compound. In addition to information on the nature of the
      (1) aglycone and the (2) glycan part, further indication of (3) sugar unit
      distribution and information on (4) the type of the glycosidic bonds can also be
      attained. Selected examples of plant extracts demonstrate the potential of the
      proposed LC-HRMS approach for the systematic screening of flavonoids. A broad
      variety of compounds were tentatively identified including both anthocyanins and
      non-anthocyanin flavonoids having various glycan moieties such as mono-, di-, and
      triglycosides with varying distributions and linkage types of carbohydrate
      moieties (O-glycosides, C-glycosides, O,C-glycosides).

PMID- 22399120
TI  - Visualization of anthocyanin species in rabbiteye blueberry Vaccinium ashei by
      matrix-assisted laser desorption/ionization imaging mass spectrometry.
AB  - Anthocyanins are naturally occurring compounds that impart color to fruits,
      vegetables, and plants, and are believed to have a number of beneficial health
      effects in both humans and animals. Because of these properties, pharmacokinetic
      analysis of anthocyanins in tissue has been performed to quantify and identify
      anthocyanin species although, currently, no methods exist for investigating
      tissue localization of anthocyanin species or for elucidating the mechanisms of
      anthocyanin activity. Imaging mass spectrometry (IMS) is powerful tool for
      determining and visualizing the distribution of a wide range of biomolecules. To
      investigate whether anthocyanin species could be identified and visualized by
      IMS, we performed matrix-assisted laser desorption/ionization (MALDI)-IMS
      analysis, by tandem mass spectrometry (MALDI-IMS-MS), of ten anthocyanin
      molecular species in rabbiteye blueberry (Vaccinium ashei). The distribution
      patterns of each anthocyanin species were different in the exocarp and endocarp
      of blueberry sections. Anthocyanin species composed of delphinidin and petunidin
      were localized mainly in the exocarp. In contrast, those species composed of
      cyanidin, peonidin, and malvidin were localized in both the exocarp and the
      endocarp. Moreover, MALDI-IMS analysis of anthocyanidins in a blueberry section
      indicated that the distribution patterns of each anthocyanidin species were
      nearly identical with those of the corresponding anthocyanins. These results
      suggested that the different distribution patterns of anthocyanin species in the
      exocarp and endocarp depended on the aglycone rather than on the sugar moieties.
      This study is the first to visualize anthocyanin molecular species in fruits.

PMID- 22399121
TI  - A study of Docetaxel-induced effects in MCF-7 cells by means of Raman
      microspectroscopy.
AB  - Chemotherapies feature a low success rate of about 25%, and therefore, the choice
      of the most effective cytostatic drug for the individual patient and monitoring
      the efficiency of an ongoing chemotherapy are important steps towards
      personalized therapy. Thereby, an objective method able to differentiate between
      treated and untreated cancer cells would be essential. In this study, we provide
      molecular insights into Docetaxel-induced effects in MCF-7 cells, as a model
      system for adenocarcinoma, by means of Raman microspectroscopy combined with
      powerful chemometric methods. The analysis of the Raman data is divided into two
      steps. In the first part, the morphology of cell organelles, e.g. the cell
      nucleus has been visualized by analysing the Raman spectra with k-means cluster
      analysis and artificial neural networks and compared to the histopathologic gold
      standard method hematoxylin and eosin staining. This comparison showed that Raman
      microscopy is capable of displaying the cell morphology; however, this is in
      contrast to hematoxylin and eosin staining label free and can therefore be
      applied potentially in vivo. Because Docetaxel is a drug acting within the cell
      nucleus, Raman spectra originating from the cell nucleus region were further
      investigated in a next step. Thereby we were able to differentiate treated from
      untreated MCF-7 cells and to quantify the cell-drug response by utilizing linear
      discriminant analysis models.

PMID- 22399122
TI  - [Chronic pain following spine surgery].
AB  - There has been an increasing trends in the procedures of spine surgery in recent
      years. Postoperative chronic pain in spine surgery can be caused by damage or
      instability of spinal column; pressure on nerves or segment of spinal cord; or
      can be due to long lasting nociception caused by inflammation, infection or
      tumour. Pain that lasts longer than 3-6 months after surgery can be define as
      postoperative chronic pain. The incidence of postoperative chronic pain after
      surgical procedures, was between 10-50%. Coping with any type of chronic pain is
      quite difficult. Chronic postoperative pain can be treated with: NSAIDs,
      paracetamol, opioids, anticonvulsants and invasive technics such as nerve blocs,
      central blocs.

PMID- 22399123
TI  - [Botulinum neuro-toxin aype-A in the treatment of chronic tension type headache
      associated with pericranial tenderness].
AB  - OBJECTIVES: Both peripheral and central nociceptive mechanisms are responsible in
      chronic TTH. Analgegics are used in the acute treatment of chronic TTH and
      antidepressants are used in prophylactic treatment. However, further studies are
      needed to bring out new treatment options. The aim of our study is to investigate
      the effectiveness of Botulinum Neuro-toxin Type-A (BoNTA) in the treatment of
      chronic TTH associated with pericranial tenderness (PT). METHODS: 14 patients
      with chronic TTH with PT were included in the study. 50 units Botox((r))
      injection was applied to the pericranial muscles (5 units for each muscles
      bilaterally: frontal, temporal, semispinalis capitis, spenius capitis and
      trapezius muscles) for each patient. Severity of headache was evaluated by VAS
      (Visual Analogue Scale) and number of days with headache per month were recorded
      before treatment and 2nd and 4th months after treatment. RESULTS: Number of days
      with headache per month were 19.57 +/- 3.25 before treatment, 15.28 +/- 4.37 at
      the 2nd month after treatment and 15.78 +/- 3.90 at the 4th month after
      treatment. Severity of headache was 65.71 +/- 9.16 before the treatment, 50.71 +/
      13.56 at the 2nd month after treatment and 54.28 +/- 10.35 at the 4th month
      after treatment (p<0.05). Frequency and severity of headache before treatment
      were significantly decreased at the 2nd month after treatment and this
      significance continued at the 4th month after treatment (p<0.05). CONCLUSION:
      BoNTA treatment may be usefull in the treatment of patients with chronic TTH
      associated with PT.

PMID- 22399124
TI  - [The role of magnesium in preventing postoperative hyperalgesia].
AB  - OBJECTIVES: Intraoperative remifentanil administration results in acute opioid
      tolerance that is manifested by increased postoperative pain, opioid requirement
      and specifically periincisional hyperalgesia. The aim of this study was to
      investigate the effect of magnesium in preventing remifentanil-induced
      hyperalgesia. METHODS: This study was performed on 60 (ASA I-II) patients planned
      for abdominal hysterectomy. Sixty patients were randomized into two equal groups.
      Before anesthesia, saline solution was given to the patients in group I (control
      group), 50 mg/kg i.v. Magnesium in group II (magnesium group). Anesthesia was
      induced with 1 ug/kg remifentanil combined with 4-5 mg/kg thiopental and 0.5
      mg/kg atracurium, maintained with 0.5 MAC sevoflurane and 0.4 ug/kg/min
      remifentanil in both groups. Sevoflurane concentration was titrated according to
      autonomic responses. Thirty minutes before the anticipated end of surgery, a 0.15
      mg/kg bolus dose of morphine was intravenously. At the end of surgery, patients
      received tramadol i.v via a PCA device. Pain score, tramadol demand and delivery
      were assessed at 2, 4, 6, 12, 24 h after surgery. Total tramadol consumption were
      recorded for 24-48 h after surgery. Periincisional hyperalgesia was assessed by
      measuring pain threshold to pressure by using an algometer and electronic von
      Frey filaments before operation and at 28-48 h postoperatively. RESULTS: The pain
      scores and cumulative tramadol consumption were significantly lower in the
      magnesium group compared with the control group (p<0.05). Pressure and mechanical
      pain threshold were significantly less at 24-48 h postoperatively in control
      group than magnesium group. CONCLUSION: Magnesium administered preemptively
      reduced remifentanil-induced hyperalgesia.

PMID- 22399125
TI  - [Comparison of bupivacaine and levobupivacaine with epidural technique for labor
      analgesia].
AB  - OBJECTIVES: The labor pain is one of the most severe pains that a woman could
      ever be suffered. Today, many medical and psychological methods are used in an
      effort to reduce labor pain.Epidural analgesia is the best current method used
      for the purposes of obstetric analgesia. METHODS: The study was carried out on 60
      ASA-I pregnant women whose 3 to 6 cm of cervical dilatation, treated in Health
      Ministry Istanbul Education and Research Hospital, Gynecology and Obstetrics
      Clinic, within vaginal labor process. With use of patient controlled epidural
      analgesia method, the bupivacaine combined with low dose fentanyl were
      administered to 30 pregnant women (Group B). Levobupivacaine, combined with low
      dose fentanyl applied with the same method was administered to another 30
      pregnant women (Group L). Between the two groups, the hemodynamic parameters on
      the mother and fetus, the course of the labor process, severity of pain, its
      influences on newborn and mother satisfaction were compared. RESULTS: In our
      study, there was no difference as to motor block development between groups, but
      the sensory block was monitored less in group L at the minutes 15, 30, 45 and 90.
      Furthermore, the 5 minutes pain score was found lower in group L. The VAS values
      at the other times were similar between groups. CONCLUSION: In conclusion, with
      the usage of 0.125% bupivacaine or 0.125% levobupivacaine, sufficient labor
      analgesia is achieved with patient controlled epidural analgesia method at the
      same side effect frequency. Consequently, both local analgesic medicines are
      seemed to be safely used in labor analgesia.

PMID- 22399126
TI  - [Venous port implantation in adult patients: retrospective evaluation].
AB  - OBJECTIVES: In the cancer therapy, the role of central venous access device has
      been increased because of factors; such as accessing to vein frequently, having
      long term therapy, using of sclerosan agents, giving much fluid. A chemoport is a
      thin, soft, plastic tube surgically implanted into a vein in chest or arm.
      Portacath doesn't have a huge size and it can generate numerous advantages. All
      the same, portacaths have risks such as infection, thrombosis, mechanical
      failure, pneumothorax, arterial injury. METHODS: A retrospective study was
      performed with analysis of records of 82 patients admitted to our clinics between
      December 2006 and November 2008 for permanent catheterisation via subclavian
      vein. RESULTS: The most frequent complication was occlusion of port (3.66%).
      Further complications were infection (2.43%), migration out of the blood vessel
      (1.22%), and catheter rupture (1.22%). CONCLUSION: As a result, made by people
      who experienced venous ports inserted, provided the opinion that a safe and
      comfortable method.

PMID- 22399127
TI  - Comparison of spring-loaded, loss of resistance and hanging drop techniques in
      lumbar epidural blocks.
AB  - OBJECTIVES: The spring-loaded syringe is a loss of resistance syringe that
      provide a more objective sign that the epidural space has been entered compared
      with the traditional techniques. The aim of this study was to compare the time
      required to locate the epidural space and the backache incidence with the spring
      loaded (SL), loss of resistance (LOR) and the hanging drop (HD) techniques for
      epidural blocks in patients undergoing transurethral resection procedure.
      METHODS: Sixty patients undergoing transurethral resections were enrolled in the
      study. The patients were randomly assigned to one of three groups. Epidural block
      was performed in the first group with a spring-loaded syringe (n=20), in the
      second group with loss-of-resistance syringe (n=20), and in the third group with
      the hanging drop technique (n=20). The required time to locate the epidural
      space, the number of attempts, the incidence of dural puncture and the backache
      incidence were assessed during the procedure and for four weeks after the
      procedure in all patients. RESULTS: The required time to locate the epidural
      space was 29.1 +/- 9.16 seconds in Group 1; 45.25 +/- 19.58 seconds in Group 2,
      and 47.35 +/- 11.42 seconds in Group 3 (p<0.001). In Group 1 this was
      significantly shorter than the other two groups. There was no significant
      difference in the number of attempts, the incidence of dural puncture and
      backache incidence between the three groups (p>0.05). CONCLUSION: The use of SL
      syringe was found to have a shorter time period to locate the epidural space when
      compared with the LOR syringe and hanging drop technique.

PMID- 22399128
TI  - Alcohol neurolysis of lateral femoral cutaneous nerve for recurrent meralgia
      paresthetica.
AB  - Meralgia paresthetica is an entrapment mononeuropathy of lateral femoral
      cutaneous nerve, which results in localized area of paresthesia and numbness on
      the anterolateral aspect of the thigh. We describe the use of alcohol neurolysis
      of lateral femoral cutaneous nerve in a 74-year-old female who presented with
      paresthesia over antero-lateral aspect of her left thigh, which was consistent
      with meralgia paresthetica. Diagnostic block with local anaesthetic confirmed the
      diagnosis but only archieved temporary pain relief. Alcohol neurolysis was then
      offered and patient responded well with no complication. The patient experienced
      prolonged pain relief at 6-month follow-up, with return of ability to ambulate
      and perform daily activity. Alcohol neurolysis of lateral femoral cutaneous nerve
      is safe, effective and able to provide sustained pain relief for recurrent
      meralgia paresthetica.

PMID- 22399129
TI  - [Combined spinal epidural anesthesia in a patient with advanced kyphoscoliosis].
AB  - Kyphoscoliosis is a progressive disease that worsens with age. While applying
      anesthesia, kyphosis and/or scoliosis can lead to difficulty in both during
      endotracheal intubation and also performing regional interventional technics. In
      addition to aging and the direct effects of deformity such as neurological
      deficities and immobility; deterioration in cardiopulmonary functions can also
      develop in these patients. In this case, we aimed to report combined spinal
      epidural anesthesia experience in a-60-year-old woman with advanced
      kyphoscoliosis who underwent left femur periprostetic fracture operation. Spinal
      anesthesia was performed through L3-L4 intervertebral space by single dose of 10
      mg %0.5 hyperbaric bupivacaine and epidural catheter was taken in for additional
      anesthesia and postoperative analgesia. Sufficient sensorial and motor block was
      provided and sensorial block was highen up to T6 dermatome level. There was no
      complication during the peroperative period and succesful anesthesia was
      established. Finally we conclude that combined spinal epidural anesthesia is a
      good alternative to general anesthesia in both reducing and preventing
      hemodynamic and respiratory complications for an elderly patient with
      kyphoscoliosis.

PMID- 22399130
TI  - Predicting the F(ab)-mediated effect of monoclonal antibodies in vivo by
      combining cell-level kinetic and pharmacokinetic modelling.
AB  - Cell-level kinetic models for therapeutically relevant processes increasingly
      benefit the early stages of drug development. Later stages of the drug
      development processes, however, rely on pharmacokinetic compartment models while
      cell-level dynamics are typically neglected. We here present a systematic
      approach to integrate cell-level kinetic models and pharmacokinetic compartment
      models. Incorporating target dynamics into pharmacokinetic models is especially
      useful for the development of therapeutic antibodies because their effect and
      pharmacokinetics are inherently interdependent. The approach is illustrated by
      analysing the F(ab)-mediated inhibitory effect of therapeutic antibodies
      targeting the epidermal growth factor receptor. We build a multi-level model for
      anti-EGFR antibodies by combining a systems biology model with in vitro
      determined parameters and a pharmacokinetic model based on in vivo
      pharmacokinetic data. Using this model, we investigated in silico the impact of
      biochemical properties of anti-EGFR antibodies on their F(ab)-mediated inhibitory
      effect. The multi-level model suggests that the F(ab)-mediated inhibitory effect
      saturates with increasing drug-receptor affinity, thereby limiting the impact of
      increasing antibody affinity on improving the effect. This indicates that
      observed differences in the therapeutic effects of high affinity antibodies in
      the market and in clinical development may result mainly from Fc-mediated
      indirect mechanisms such as antibody-dependent cell cytotoxicity.

PMID- 22399131
TI  - Evidence of Fe3+ interaction with the plug domain of the outer membrane
      transferrin receptor protein of Neisseria gonorrhoeae: implications for Fe
      transport.
AB  - Neisseria gonorrhoeae is an obligate pathogen that hijacks iron from the human
      iron transport protein, holo-transferrin (Fe(2)-Tf), by expressing TonB-dependent
      outer membrane receptor proteins, TbpA and TbpB. Homologous to other TonB
      dependent outer membrane transporters, TbpA is thought to consist of a beta
      barrel with an N-terminal plug domain. Previous reports by our laboratories show
      that the sequence EIEYE in the plug domain is highly conserved among various
      bacterial species that express TbpA and plays a crucial role in iron utilization
      for gonococci. We hypothesize that this highly conserved EIEYE sequence in the
      TbpA plug, rich in hard oxygen donor groups, binds with Fe(3+) through the
      transport process across the outer membrane through the beta-barrel.
      Sequestration of Fe(3+) by the TbpA-plug supports the paradigm that the ferric
      iron must always remain chelated and controlled throughout the transport process.
      In order to test this hypothesis here we describe the ability of both the
      recombinant wild-type plug, and three small peptides that encompass the sequence
      EIEYE of the plug, to bind Fe(3+). This is the first report of the
      expression/isolation of the recombinant wild-type TbpA plug. Although CD and
      SUPREX spectroscopies suggest that a non-native structure is observed for the
      recombinant plug, fluorescence quenching titrations indicate that the wild-type
      recombinant TbpA plug binds Fe (3+) with a conditional log K(d) = 7 at pH 7.5,
      with no evidence of binding at pH 6.3. A recombinant TbpA plug with mutated
      sequence (NEIEYEN -> NEIAAAN) shows no evidence of Fe(3+) binding under our
      experimental set up. Interestingly, in silico modeling with the wild-type plug
      also predicts a flexible loop structure for the EIEYE sequence under native
      conditions which once again supports the Fe(3+) binding hypothesis. These in
      vitro observations are consistent with the hypothesis that the EIEYE sequence in
      the wild-type TbpA plug binds Fe(3+) during the outer membrane transport process
      in vivo.

PMID- 22399134
TI  - Development and validation of the current concept of major depression.
AB  - The operational diagnostic criteria for major depression have remained more or
      less the same in the past 40 years. However, the threshold for the diagnosis
      fixed by operational definitions has been criticized for either being too high,
      excluding many depressive states which do not differ from currently defined major
      depression on several variables, or too low, so that the milder cases receiving
      the diagnosis do not respond to antidepressants better than to placebo.
      Furthermore, it has been stated that current operational criteria do not convey
      anymore the gestalt of the depressive syndrome, and that they lead to the
      inclusion under the heading of depression of several homeostatic responses to
      adverse life events. This paper reviews the development and validation of the
      current concept of major depression and identifies priorities for future
      research.

PMID- 22399132
TI  - Quality of life, fatigue and depression in Italian long-term breast cancer
      survivors.

PMID- 22399135
TI  - Isolation of metallothionein genes and in silico structural characterization of
      their proteins using molecular modeling from yak (Bos grunniens).
AB  - Yak metallothioneins (BgMTs) are cysteine-rich metal-chelating proteins with
      highly conserved cysteine residues in their amino acid sequences. The 3D
      structures of the Cd(7)-BgMTs reconstructed by molecular modeling included two
      domains: the beta-domain with M(3)(S(cys))(9) metal-thiolate clusters and the
      alpha-domain with M(4)(S(cys))(11) metal-thiolate clusters. An unusual variant
      was found at position 30 (Cys30->Ser30) in BgMT-III, which is usually conserved
      in the mammalian MT-I/-II (Cys29) and MT-III (Cys30). The variant residue of BgMT
      III may play a key role in yak genetic evolution, metal-binding activity, dynamic
      conformation, and heavy metal metabolism. BgMT-III contained a Thr insertion at
      position 5 (T(5)), which may loosen the structure of the beta-domain of BgMT-III,
      and a conserved C(6)PCP(9) motif, which may provide an interacting surface for
      protein-protein interactions. There is also an acidic hexapeptide insertion
      (E(55)GAEAE(60)) that could regulate the particular interdomain interactions and
      lead to the conformational change in the beta-domain.

PMID- 22399133
TI  - The instrumented fetal sheep as a model of cerebral white matter injury in the
      premature infant.
AB  - Despite advances in neonatal intensive care, survivors of premature birth remain
      highly susceptible to unique patterns of developmental brain injury that manifest
      as cerebral palsy and cognitive-learning disabilities. The developing brain is
      particularly susceptible to cerebral white matter injury related to hypoxia
      ischemia. Cerebral white matter development in fetal sheep shares many anatomical
      and physiological similarities with humans. Thus, the fetal sheep has provided
      unique experimental access to the complex pathophysiological processes that
      contribute to injury to the human brain during successive periods in development.
      Recent refinements have resulted in models that replicate major features of acute
      and chronic human cerebral injury and have provided access to complex clinically
      relevant studies of cerebral blood flow and neuroimaging that are not feasible in
      smaller laboratory animals. Here, we focus on emerging insights and methodologies
      from studies in fetal sheep that have begun to define cellular and vascular
      factors that contribute to white matter injury. Recent advances include spatially
      defined measurements of cerebral blood flow in utero, the definition of cellular
      maturational factors that define the topography of injury and the application of
      high-field magnetic resonance imaging to define novel neuroimaging signatures for
      specific types of chronic white matter injury. Despite the higher costs and
      technical challenges of instrumented preterm fetal sheep models, they provide
      powerful access to clinically relevant studies that provide a more integrated
      analysis of the spectrum of insults that appear to contribute to cerebral injury
      in human preterm infants.

PMID- 22399136
TI  - H2O2 triggered sol-gel transition used for visual detection of glucose.
AB  - A new approach for the visual detection of glucose based on a H(2)O(2) triggered
      sol-gel transition in combination with modified gold nanoparticles is reported.

PMID- 22399137
TI  - A convenient route to 4-carboxy-4-anilidopiperidine esters and acids.
AB  - The route selection and development of a convenient synthesis of 4-carboxy-4
      anilidopiperidines is described. Previous routes were hampered by the low yield
      of the target esters as well as the inability to convert the esters to the
      required free acids. Considerations for large-scale production led to a modified
      synthesis that utilised a tert-butyl ester of 4-carboxy-4-anilidopiperidines
      which resulted in a dramatic increase in the overall yield of the target N
      propionylated- 4-anilidopiperidine-4-carboxylic acids and their corresponding
      methyl esters. These compounds are now available for use as precursors and
      reference standards, of particular value for the production of 11C and 18F
      labelled 4-carboxy-4-anilidopiperidine radiotracers.

PMID- 22399138
TI  - IMB2026791, a xanthone, stimulates cholesterol efflux by increasing the binding
      of apolipoprotein A-I to ATP-binding cassette transporter A1.
AB  - It is known that the ATP-binding cassette transporter A1 (ABCA1) plays a major
      role in cholesterol homeostasis and high density lipoprotein (HDL) metabolism.
      Several laboratories have demonstrated that ABCA1 binding to lipid-poor
      apolipoprotein A-I (apoA-I) will mediate the assembly of nascent HDL and cellular
      cholesterol efflux, which suggests a possible receptor-ligand interaction between
      ABCA1 and apoA-I. In this study, a cell-based-ELISA-like high-throughput
      screening (HTS) method was developed to identify the synthetic and natural
      compounds that can regulate binding activity of ABCA1 to apoA-I. The cell-based
      ELISA-like high-throughput screen was conducted in a 96-well format using Chinese
      hamster ovary (CHO) cells stably transfected with ABCA1 pIRE2-EGFP (Enhanced
      Green Fluorecence Protein) expression vector and the known ABCA1 inhibitor
      glibenclamide as the antagonist control. From 2,600 compounds, a xanthone
      compound (IMB 2026791) was selected using this HTS assay, and it was proved as an
      apoA-I binding agonist to ABCA1 by a flow cytometry assay and western blot
      analysis. The [3H] cholesterol efflux assay of IMB2026791 treated ABCA1-CHO cells
      and PMA induced THP-1 macrophages (human acute monocytic leukemia cell) further
      confirmed the compound as an accelerator of cholesterol efflux in a dose
      dependent manner with an EC(50) of 25.23 MUM.

PMID- 22399140
TI  - Key to xenobiotic carotenoids.
AB  - A listing of carotenoids with heteroatoms (X = F, Cl, Br, I, Si, N, S, Se, Fe)
      directly attached to the carotenoid carbon skeleton has been compiled. The 178
      listed carotenoids with C, H, X atoms demonstrate that the classical division of
      carotenoids into hydrocarbon carotenoids (C, H) and xanthophylls (C, H, O) has
      become obsolete.

PMID- 22399139
TI  - Site-specific incorporation of functional components into RNA by an unnatural
      base pair transcription system.
AB  - Toward the expansion of the genetic alphabet, an unnatural base pair between 7-(2
      thienyl)imidazo[4,5-b]pyridine (Ds) and pyrrole-2-carbaldehyde (Pa) functions as
      a third base pair in replication and transcription, and provides a useful tool
      for the site-specific, enzymatic incorporation of functional components into
      nucleic acids. We have synthesized several modified-Pa substrates, such as
      alkylamino-, biotin-, TAMRA-, FAM-, and digoxigenin-linked PaTPs, and examined
      their transcription by T7 RNA polymerase using Ds-containing DNA templates with
      various sequences. The Pa substrates modified with relatively small functional
      groups, such as alkylamino and biotin, were efficiently incorporated into RNA
      transcripts at the internal positions, except for those less than 10 bases from
      the 3'-terminus. We found that the efficient incorporation into a position close
      to the 3'-terminus of a transcript depended on the natural base contexts
      neighboring the unnatural base, and that pyrimidine-Ds-pyrimidine sequences in
      templates were generally favorable, relative to purine-Ds-purine sequences. The
      unnatural base pair transcription system provides a method for the site-specific
      functionalization of large RNA molecules.

PMID- 22399141
TI  - Mutations in PRRT2 responsible for paroxysmal kinesigenic dyskinesias also cause
      benign familial infantile convulsions.
AB  - Paroxysmal kinesigenic dyskinesia (PKD (MIM128000)) is a neurological disorder
      characterized by recurrent attacks of involuntary movements. Benign familial
      infantile convulsion (BFIC) is also one of a neurological disorder characterized
      by clusters of epileptic seizures. The BFIC1 (MIM601764), BFIC2 (MIM605751) and
      BFIC4 (MIM612627) loci have been mapped to chromosome 19q, 16p and 1p,
      respectively, while BFIC3 (MIM607745) is caused by mutations in SCN2A on
      chromosome 2q24. Furthermore, patients with BFIC have been observed in a family
      concurrently with PKD. Both PKD and BFIC2 are heritable paroxysmal disorders and
      map to the same region on chromosome 16. Recently, the causative gene of PKD, the
      protein-rich transmembrane protein 2 (PRRT2), has been detected using whole-exome
      sequencing. We performed mutation analysis of PRRT2 by direct sequencing in 81
      members of 17 families containing 15 PKD families and two BFIC families. Direct
      sequencing revealed that two mutations, c.649dupC and c.748C>T, were detected in
      all members of the PKD and BFIC families. Our results suggest that BFIC2 is
      caused by a truncated mutation that also causes PKD. Thus, PKD and BFIC2 are
      genetically identical and may cause convulsions and involuntary movements via a
      similar mechanism.

PMID- 22399142
TI  - A genome-wide association study identifies novel susceptibility genetic variation
      for thyrotoxic hypokalemic periodic paralysis.
AB  - Several lines of evidence have pointed out that genetic components have roles in
      thyrotoxic hypokalemic periodic paralysis (TTPP). In this study, for the first
      time we performed genome-wide association study (GWAS) in male hyperthyroid
      subjects in order to identify genetic loci conferring susceptibility to TTPP. We
      genotyped 78 Thai male TTPP cases and 74 Thai male hyperthyroid patients without
      hypokalemia as controls with Illumina Human-Hap610 Genotyping BeadChip. Among the
      SNPs analyzed in the GWAS, rs312729 at chromosome 17q revealed the lowest P-value
      for association (P=2.09 * 10(-7)). After fine mapping for linkage disequilibrium
      blocks surrounding the landmark SNP, we found a significant association of
      rs623011; located at 75 kb downstream of KCNJ2 on chromosome 17q, reached the
      GWAS significance after Bonferroni's adjustment (P=3.23 * 10(-8), odds ratio
      (OR)=6.72; 95% confidence interval (CI)=3.11-14.5). The result was confirmed in
      an independent cohort of samples consisting of 28 TTPP patients and 48 controls
      using the same clinical criteria diagnosis (replication analysis P=3.44 * 10(-5),
      OR=5.13; 95% CI=1.87-14.1; combined-analysis P=3.71 * 10(-12), OR=5.47; 95%
      CI=3.04-9.83).

PMID- 22399143
TI  - The transition strength from solid to liquid colloidal dipolar clusters in
      precessing magnetic fields.
AB  - We report on the rotation of colloidal clusters of diamagnetic beads and of
      mixtures of paramagnetic and diamagnetic beads in a ferrofluid in a precessing
      external magnetic field. The precession angle of the external field is a control
      parameter determining the stability of the cluster. Clusters become locally
      unstable when the local precession angle reaches the magic angle. Cluster shape
      dependent depolarization fields lead to a deviation of the local from the
      external precession angle such that close to the external magic angle different
      cluster shapes might coexist. For this reason cluster transitions are weakly or
      strongly first-order transitions. If the transition is weakly first order a
      critical speeding up of the cluster rotation is observed. No speeding up occurs
      for strongly first-order cluster transitions with hysteresis. The strength of the
      first-order transition is controlled by the size of the core of the cluster.

PMID- 22399145
TI  - Palladium(II) thiocarboxamide complexes: synthesis, characterisation and
      application to catalytic Suzuki coupling reactions.
AB  - A simple route to synthesise palladium(II) complexes from the reaction of N
      substituted pyridine-2-thiocarboxamide ligands and PdCl(2)(PPh(3))(2) has been
      developed. The new complexes are very soluble in common solvents and have been
      fully characterised (elemental analysis, FT-IR, (1)H, (31)P, (13)C-NMR),
      including an X-ray diffraction analysis. The molecular structures of all the
      complexes were determined and reveal the presence of square planar geometry
      around Pd with little distortion. The complexes were tested in the Suzuki
      coupling of electronically deactivated aryl and heteroaryl bromides and were
      found to have much greater activity, without using any promoting additives or
      phase transfer agent under aerobic conditions. Higher reaction rates are obtained
      by varying R substituents on the aromatic ring of pyridine-2-thiocarboxamide. The
      effect of other variables on the cross-coupling reaction, such as temperature,
      solvent and base, is also reported.

PMID- 22399144
TI  - Metal pollution does not bias offspring sex ratio in great tit (Parus major).
AB  - PURPOSE: We measured offspring sex ratios in a resident insectivorous passerine
      bird, the Great tit Parus major, to find out whether metal pollution around a
      Finnish copper smelter would bias sex ratios in this territorial forest bird
      species. Besides a direct effect of pollutants, we were interested in possible
      indirect effects of pollution-related resource limitation, i.e., changes in food
      quality and quantity, on sex ratio. METHODS: We manipulated the diet quantity and
      quality (carotenoid levels) of P. major nestlings in polluted and unpolluted
      environments to find out if variation in dietary resource levels has any effect
      on fledgling sex ratios. Faecal metal levels of nestlings were analysed to
      monitor the level of pollution exposure at each territory. Near the time of
      fledging (at the age of 15 days), feather samples were collected for molecular
      sex determination. RESULTS: We did not find any association between metal
      exposure levels and offspring sex ratio, and thus, our results do not support the
      hypothesis that metal pollution would have direct effects on P. major offspring
      sex ratio. We found that, irrespective of pollution level, high nestling
      mortality was associated with male-biased sex ratio, most likely due to sex
      specific mortality. Our feeding treatment, however, showed no significant effects
      on offspring sex ratio, possibly because natural variation in food availability
      outweighed the effect of our food manipulation on nestling mortality.
      CONCLUSIONS: We conclude that metal exposure at the levels found in our study
      area does not bias fledgling sex ratios in this species, but biased sex ratios
      may follow under natural or pollution-related resource limitation.

PMID- 22399146
TI  - Erwin Stransky (1877-1962).

PMID- 22399147
TI  - Effect of stem cell transplantation for B-cell malignancies on disease course of
      associated polyneuropathy.
AB  - B cell dyscrasias are often refractory to medical treatments, and hematological
      stem cell therapy (SCT) may be warranted. It is not clear whether an associated
      polyneuropathy may also profit from SCT. In exceptional cases SCT has been tried
      in patients with monoclonal gammopathy and progressive polyneuropathy refractory
      to medical treatments. In a cohort of 225 patients with monoclonal gammopathy and
      polyneuropathy, we selected the six patients who underwent SCT and
      retrospectively examined the effects of SCT on the disease course of the
      associated polyneuropathy. In all patients except one, the indication for SCT was
      hemato-oncological (multiple myeloma in 4 patients and primary AL amyloidosis in
      1). The remaining patient had an IgG monoclonal gammopathy of undetermined
      significance and a progressive and painful polyneuropathy for which she was
      treated with SCT. SCT led to improvement of motor scores and autonomic symptoms
      in one patient; three patients experienced improvement of neuropathic pain or
      sensory deficits but showed further progression of weakness. One patient showed
      no improvement at all. One patient died within 100 days after SCT. In conclusion,
      SCT as a treatment of refractory hematological malignancy may occasionally have a
      positive effect on the associated progressive polyneuropathy, although the
      benefits are very limited and the treatment-related mortality is high.

PMID- 22399148
TI  - A 1,3-phenyl-linked hydantoin oligomer scaffold as a beta-strand mimetic.
AB  - A synthetic scaffold that mimics a peptide beta-strand has been designed and
      synthesised based on a 1,3-phenyl-linked hydantoin oligomer. The conformational
      preferences of this oligomer were investigated using molecular modelling and
      solution NMR experiments and suggest a planar conformation that accurately mimics
      the i, i + 2 and i + 4 residues of a peptide beta-strand.

PMID- 22399150
TI  - Pd(II)-catalyzed direct C5-arylation of azole-4-carboxylates through double C-H
      bond cleavage.
AB  - The first palladium-catalyzed direct C5-arylation of azole-4-carboxylates with
      simple unactivated arenes through double C-H bond cleavage is realized. This
      protocol provided a straightforward access to diverse 5-arylsubstituted azole-4
      carboxylic derivatives with good functional group tolerance.

PMID- 22399149
TI  - Role of wobble base pair geometry for codon degeneracy: purine-type bases at the
      anticodon wobble position.
AB  - Codon degeneracy is a key feature of the genetic code, explained by Crick (J Mol
      Biol 19:548-555, 1966) in terms of imprecision of base pairing at the codon third
      position (the wobble position) of the codon-anticodon duplex. The Crick wobble
      rules define, but do not explain, which base pairs are allowed/disallowed at the
      wobble position of this duplex. This work examines whether the H-bonded
      configurations of solitary RNA base pairs can in themselves help decide which
      base pairs are allowed at the wobble position during codon-anticodon pairing.
      Taking the purine-type bases guanine, hypoxanthine, queuine and adenine as
      anticodon wobble bases, H-bonded pairing energies and optimized configurations of
      numerous RNA base pairs are calculated in gas and modeled aqueous phase at the
      B3LYP/6-31 G(d,p) level. Calculated descriptors of alignment of these solitary
      base pairs are able to screen between allowed and disallowed base pairs for all
      cases studied here, except two cases which invoke base-sugar interactions in the
      codon wobble nucleoside. The exclusion of adenine from the anticodon wobble
      position cannot be explained on the basis of pairing facility or base pair
      geometry. These DFT results thus account for the specificity and degeneracy of
      the genetic code for all cases involving guanine, hypoxanthine and queuine as
      anticodon wobble bases.

PMID- 22399151
TI  - Recurrent bone marrow aplasia secondary to nilotinib in a patient with chronic
      myeloid leukemia: a case report.
AB  - Nilotinib is a potent tyrosine kinase inhibitor of breakpoint cluster region
      abelson (BCR-ABL), which has been approved as front-line therapy for newly
      diagnosed chronic myeloid leukemia in chronic phase and as second-line therapy
      after imatinib failure in chronic or accelerated phase chronic myeloid leukemia.
      Tyrosine kinase inhibitors have been associated with myelosuppression and grade 3
      or grade 4 cytopenias are not uncommon in chronic myeloid leukemia patients
      treated with these drugs. There are a few reports of imatinib-associated bone
      marrow aplasia, but to our knowledge only one reported case of bone marrow
      aplasia associated with nilotinib. Herein, we report a 49-year-old male patient
      with chronic phase chronic myeloid leukemia, who developed severe bone marrow
      aplasia due to nilotinib. Possible mechanisms for this significant adverse drug
      reaction are discussed along with a review of literature.

PMID- 22399152
TI  - ABO blood types are associated with risk of idiopathic venous thromboembolism in
      the Korean population. A report from the Korean Venous Thromboembolism Working
      Party (KVTEWP).

PMID- 22399153
TI  - An increased risk for fractures: another cause of frailty in HIV-infected
      subjects.

PMID- 22399154
TI  - Postoperative hungry bone syndrome in patients with secondary hyperparathyroidism
      of renal origin.
AB  - BACKGROUND: Hungry bone syndrome (HBS) is a postoperative condition of severe
      hypocalcemia that can be seen in patients who have undergone parathyroidectomy
      (PTX) for secondary hyperparathyroidism (2HPT) of renal origin. This study
      examines HBS in patients after PTX for 2HPT. METHODS: Prospectively collected
      data was retrospectively reviewed in patients who underwent PTX for 2HPT of renal
      origin at a single institution. HBS was defined as the need for additional days
      of hospitalization or readmission for intravenous calcium supplementation due to
      clinical symptoms of hypocalcemia, including tingling, muscle spasms, and bone
      pain and/or immediate postoperative low serum calcium <=7.5 mg/dl. RESULTS: Of 79
      patients who underwent PTX for 2HPT, 27.8% (n = 22) experienced HBS. Young age
      (<=45 years, p = 0.02) was the only preoperative variable that predicted HBS.
      Most patients developed HBS within 18 h after surgery and required a prolonged
      hospital stay (19/22) compared to those requiring hospital readmission within the
      first 7 days (3/22). Initial postoperative serum calcium levels within 18 h of
      surgery were significantly lower in those patients who developed HBS (7.1 vs. 8.3
      mg/dl, p = 0.001), and those patients also had a greater absolute decrease in
      serum calcium (2.8 vs. 3.5 mg/dl, p = 0.04). CONCLUSION: HBS develops in a
      significant proportion of patients generally within the first 18 h after subtotal
      PTX for 2HPT. The only identifiable preoperative risk factor for HBS was young
      age. Additionally, low initial calcium levels and greater absolute decrease in
      serum calcium may help identify those patients that will develop HBS requiring
      judicious calcium supplementation.

PMID- 22399155
TI  - A prospective evaluation of quick intraoperative parathyroid hormone assay at the
      time of skin closure in predicting clinically relevant hypocalcemia after
      thyroidectomy.
AB  - BACKGROUND: Post-thyroidectomy hypocalcemia is a major contributing factor in
      delayed hospital discharge and dissuading surgeons from ambulatory thyroidectomy.
      We prospectively evaluated the accuracy and reliability of quick parathyroid
      hormone level measurement at skin closure (PTH-SC) in predicting clinically
      relevant hypocalcemia (i.e., patients requiring calcium +/- calcitriol
      supplements on hospital discharge). METHODS: Of the 117 patients who underwent a
      total or completion total thyroidectomy and PTH-SC, 17 (14.5 %) had hypocalcemic
      symptoms or adjusted calcium <1.90 mmol/L requiring calcium and/or calcitriol
      supplements on discharge. Serum calcium was checked regularly in the
      perioperative period until stabilization and an additional quick PTH was checked
      on the following morning (PTH-D1). Univariate and multivariate analyses were
      performed to evaluate potential preoperative clinicopathologic factors and
      postoperative day 0 biochemical indicators. Youden's index and the area under the
      ROC curve (AUC) were used to determine the best cutoff value and predictability
      of significant variables or criteria, respectively. RESULTS: In the multivariate
      analysis, low preoperative adjusted calcium (p = 0.041) and low PTH-SC (p =
      0.001) were the two independent variables associated with hypocalcemia. PTH-SC
      (<=1 or >1 pmol/L) had a higher specificity (95.0 %) and AUC (0.887) than serial
      calcium monitoring or PTH-D1 alone. Although 3/98 of patients with PTH-SC >1
      pmol/L required calcium supplements on discharge, they required only the minimum
      amount to maintain normocalcemia. CONCLUSION: PTH-SC is an accurate and reliable
      means of predicting clinically relevant hypocalcemia. It would be reasonable to
      discharge those with PTH-SC >1 pmol/L on the same operative day as the risk of
      life-threatening hypocalcemia would seem unlikely.

PMID- 22399156
TI  - Functional self-assembled DNA nanostructures for molecular recognition.
AB  - Nucleic acids present a wonderful toolkit of structural motifs for
      nanoconstruction. Functional DNA nanostructures can enable protein recognition by
      the use of aptamers attached to a basic core shape formed by DNA self-assembly.
      Here, we present a facile, programmable strategy for the assembly of discrete
      aptamer-tagged DNA shapes and nanostructures that can function for molecular
      recognition and binding in an aqueous environment. These nanostructures,
      presented here to bind two different protein targets, are easily synthesized in
      large numbers, and are portable and stable over long periods of time. This
      construction modality can facilitate on-demand production of libraries of diverse
      shapes to recognize and bind proteins or catalyze reactions via functional
      nucleic acid tags.

PMID- 22399157
TI  - Utility of augmented reality system in hepatobiliary surgery.
AB  - BACKGROUND/PURPOSE: The aim of this study was to evaluate the utility of an image
      display system for augmented reality in hepatobiliary surgery under laparotomy.
      METHODS: An overlay display of organs, vessels, or tumor was obtained using a
      video see-through system as a display system developed at our institute.
      Registration between visceral organs and the surface-rendering image
      reconstructed by preoperative computed tomography (CT) was carried out with an
      optical location sensor. Using this system, we performed laparotomy for a patient
      with benign biliary stricture, a patient with gallbladder carcinoma, and a
      patient with hepatocellular carcinoma. RESULTS: The operative procedures
      performed consisted of choledochojejunostomy, right hepatectomy, and microwave
      coagulation therapy. All the operations were carried out safely using images of
      the site of tumor, preserved organs, and resection aspect overlaid onto the
      operation field images observed on the monitors. The position of each organ in
      the overlaid image closely corresponded with that of the actual organ.
      Intraoperative information generated from this system provided us with useful
      navigation. However, several problems such as registration error and lack of
      depth knowledge were noted. CONCLUSION: The image display system appeared to be
      useful in performing hepatobiliary surgery under laparotomy. Further improvement
      of the system with individualized function for each operation will be essential,
      with feedback from clinical trials in the future.

PMID- 22399158
TI  - Contrast-enhanced intraoperative ultrasound for hepatocellular carcinoma: high
      sensitivity of diagnosis and therapeutic impact.
AB  - BACKGROUND: Postoperative early recurrence is a crucial issue in the treatment of
      hepatocellular carcinoma (HCC) patients. Some early recurrences seem to occur
      from minute tumors which were overlooked during both preoperative and
      intraoperative investigations. Therefore, it is urgently necessary to increase
      detectability of minute HCCs during operation. If they could be detected and
      resected during surgery, the prognosis should be improved. The purpose of this
      study is to investigate the usefulness of contrast-enhanced intraoperative
      ultrasound (CEIOUS) for the diagnosis and treatment of HCC. METHODS:
      Institutional ethics committee approval and informed consent were obtained. Fifty
      two patients (mean age 65 years; 38 males and 14 females) who underwent liver
      resection with either preoperative computed tomography during angiography (CTA)
      or CEIOUS with Sonazoid (perflubutane microbubble contrast agent) were studied.
      We determined the presence of HCC on the basis of the histopathological findings
      of resected specimens. RESULTS: The sensitivity of CEIOUS [97.6% (95% CI 91.8
      99.4)] was higher than that of CTA [89.4% (95% CI 81.1-94.3)]. The positive
      predictive values of CEIOUS [91.2% (95% CI 83.6-95.5) and CTA [91.6% (95% CI 83.6
      95.9)] were similar. Eight new HCCs from 7 patients, which accounted for 9.4%
      (8/85) of the total HCCs, were correctly detected and diagnosed by CEIOUS, and we
      performed an additional partial hepatectomy in 3 of these 7 patients.
      CONCLUSIONS: CEIOUS with Sonazoid provided increased sensitivity of detection of
      small HCCs compared with preoperative CTA, thereby leading to a more appropriate
      surgical procedure and contributing to complete tumor removal.

PMID- 22399159
TI  - Simian varicella virus infection of Chinese rhesus macaques produces ganglionic
      infection in the absence of rash.
AB  - Varicella-zoster virus (VZV) causes varicella (chickenpox), becomes latent in
      ganglia along the entire neuraxis, and may reactivate to cause herpes zoster
      (shingles). VZV may infect ganglia via retrograde axonal transport from infected
      skin or through hematogenous spread. Simian varicella virus (SVV) infection of
      rhesus macaques provides a useful model system to study the pathogenesis of human
      VZV infection. To dissect the virus and host immune factors during acute SVV
      infection, we analyzed four SVV-seronegative Chinese rhesus macaques infected
      intratracheally with cell-associated 5 * 103 plaque-forming units (pfu) of SVV
      expressing green fluorescent protein (n = 2) or 5 * 104 pfu of wild-type SVV (n =
      2). All monkeys developed viremia and SVV-specific adaptive B- and T-cell immune
      responses, but none developed skin rash. At necropsy 21 days postinfection, SVV
      DNA was found in ganglia along the entire neuraxis and in viscera, and SVV RNA
      was found in ganglia, but not in viscera. The amount of SVV inoculum was
      associated with the extent of viremia and the immune response to virus. Our
      findings demonstrate that acute SVV infection of Chinese rhesus macaques leads to
      ganglionic infection by the hematogenous route and the induction of a virus
      specific adaptive memory response in the absence of skin rash.

PMID- 22399160
TI  - Spinal motor control differences between the sexes.
AB  - Activity-related knee joint dysfunction is more prevalent in females than males.
      One explanation for the discrepancy is differences in movement patterns between
      the sexes. However, the underlying mechanisms responsible for these differences
      remain unidentified. This study tested spinal motor control mechanisms
      influencing motor neuron pool output and subsequent muscle activation in 17 males
      and 17 females. The following variables were assessed at the soleus: the gain of
      the unconditioned H-reflex, gain of both intrinsic pre-synaptic inhibition (IPI)
      and extrinsic pre-synaptic inhibition (EPI), the level of recurrent inhibition
      (RI), the level of supraspinal drive determined by the ratio of the Vmax:Mmax (V
      wave), electromechanical delay (EMD) and the rate of force development (RFD). The
      Wilks Lambda multivariate test of overall differences among groups was
      significant (p = 0.031). Univariate between-subjects tests revealed males had
      greater RI (p = 0.042). However, the sexes did not differ on any of the other
      variables tested. In conclusion, the sexes differ on modulation of spinal motor
      control. Specifically, RI, a post-synaptic regulator of force output, was greater
      in males.

PMID- 22399161
TI  - Religiosity and HIV-related drug risk behavior: a multidimensional assessment of
      individuals from communities with high rates of drug use.
AB  - We examined the relationship between religiosity and HIV-related drug risk
      behavior among individuals from communities with high rates of drug use who
      participated in the SHIELD (Self-Help in Eliminating Life-Threatening Disease)
      study. This analysis examined the dimensions of religious ideation, religious
      participation, and religious support separately to further understand the
      relationship with risk taking. Results indicate that greater religious
      participation appeared to be the dimension most closely associated with drug
      behaviors. Specifically, we found that those with greater religious participation
      are significantly less likely to report recent opiates or cocaine use; injection
      drug use; crack use; and needle, cotton or cooker sharing. Future work to
      understand the nature of these associations will assist in the development of
      interventions in communities with high rates of drug use. 

PMID- 22399162
TI  - Stability and distribution of steady-state somatosensory evoked potentials
      elicited by vibro-tactile stimulation.
AB  - Steady-state somatosensory evoked potentials (SSSEPs) have been elicited applying
      vibro-tactile stimulation to all fingertips of the right hand. Nine healthy
      subjects participated in two sessions within this study. All fingers were
      stimulated 40 times with a 200-Hz carrier frequency modulated with a rectangular
      signal. The frequencies of the rectangular signal ranged between 17 and 35 Hz in
      2 Hz steps. Relative band power tuning curves were calculated, introducing two
      different methods. Person-specific resonance-like frequencies were selected based
      on the data from the first session. The selected resonance-like frequencies were
      compared with the second session using an ANOVA for repeated measures to
      investigate the stability of SSSEPs over time. To determine, if SSSEPs can be
      classified with a classifier based on unseen data, an LDA classifier was trained
      with data from the first and applied to data from the second session. Person
      specific resonance-like frequencies within a range from 19 to 29 Hz were found.
      The relative band power of the resonance-like frequencies did not differ
      significantly between the two sessions. Significant differences were found for
      the two methods and the used channels. SSSEPs were classified with a hit rate
      from 51 to 96 %.

PMID- 22399163
TI  - Diagnosis of Parkinson's disease using electrovestibulography.
AB  - In this paper, a new method for diagnosis of Parkinson's disease (PD) based on
      the analysis of electrovestibulography (EVestG) signals is introduced. EVestG
      signals are in fact the vestibular response modulated by more cortical brain
      signals; they are recorded from the ear canal. EVestG data of 20 individuals with
      PD and 28 healthy controls were adopted from a previous study. The field
      potentials and their firing pattern in response to whole body tilt stimuli from
      both left and right ears were extracted. We investigated several statistical and
      fractal features of the field potentials and also their firing interval
      histograms followed by one-way analysis of variance to select pairs of features
      showing the most significant differences between individuals with Parkinson
      disease and the age-matched controls. Linear discriminant analysis classification
      was applied to every selected feature using a leave-one-out routine. The result
      of each feature's classifier was used in a heuristic average voting system to
      diagnose PD patients. The results show more than 95% accuracy for PD diagnosis.
      Given that the patients were at different stage of disease, the high accuracy of
      the results is encouraging for continuing exploration of the EVestG application
      to PD diagnosis as it may provide a quick and non-invasive screening tool.

PMID- 22399164
TI  - Evaluating the nucleus effect on the dynamic indentation behavior of cells.
AB  - The effect of the nucleus on the cell mechanical behavior was investigated based
      on the dynamic indentation response of cells under a spherical tip. A "two
      component" cell model (including cytoplasm and nucleus) is used, and the dynamic
      indentation behavior is studied by a semiempirical method, which is established
      based on fitting the numerical simulation results of the quasi-static indentation
      response of cells. We found that the "routine analysis" (based on the Hertz's
      contact solution of homogeneous model) significantly overestimated the nucleus
      effect on the overall cell indentation response due to the effects of the Hertz
      contact radius and the substrate stiffening. These effects are significantly
      stronger in the "two-component" cell model than in the homogeneous model. The
      inaccuracy created by the "routine analysis" slightly increases with the modulus
      ratio of nucleus to cytoplasm and the volume fraction of nucleus. Finally, the
      error sensitivity to the geometrical parameters used in the model is discussed,
      which shows the indentation analysis is not very sensitive to these parameters,
      and the reasonable assumptions for these parameters are effective. This
      systematic analysis can provide a useful guideline to understanding the
      mechanical behavior of cells and nuclei.

PMID- 22399165
TI  - [Investigation of the frequency of PER-1 type beta-lactamase and antimicrobial
      resistance rates in nosocomial isolates of Pseudomonas aeruginosa].
AB  - Pseudomonas aeruginosa which is a common cause of nosocomial infections, usually
      leads to treatment difficulties due to multi-drug resistance. PER-1 type extended
      spectrum beta-lactamase (ESBL) producing bacteria are shown to be common in
      Turkey. Since limited number of antibiotics such as antipseudomonal penicillins,
      cephalosporins, aminoglycosides, fluoroquinolones and carbapenems are available
      for the treatment of P.aeruginosa infections, it is essential to monitor and
      eventually control the spread of antibiotic resistance genes. The aims of this
      study were to investigate the presence of PER-1 type ESBLs in nosocomial
      P.aeruginosa isolates and to evaluate their resistance to some commonly used
      antibiotics. A total of 110 P.aeruginosa strains isolated from clinical samples
      [40 urine, 26 exudate, 20 blood, 24 others (sputum, tracheal aspirate, tissue
      biopsy, cerebrospinal fluid, pleural fluid, conjunctiva)] of the inpatients who
      were proven to have nosocomial infections in Ondokuz Mayis University Faculty of
      Medicine Hospital between May 2002-June 2003 were included in the study.
      Identification of the isolates was performed by ATB system ID 32 GN (bio-Merieux,
      France). Antibiotic susceptibilities were detected by standard disk diffusion
      method and PER-1 type ESBL was searched by polymerase chain reaction using PER-1
      and PER- 2 primers. PER-1 positivity was detected in 62 of 110 (56.4%)
      P.aeruginosa isolates and 51 of 65 (78.5%) ceftazidime-resistant strains. The
      highest susceptibility rate was detected for ciprofloxacin (76.4%), while the
      lowest susceptibility rate was for ticarcillin-clavulanic acid (22.7%). Rates of
      resistance to beta-lactam agents (excluding piperacillin/tazobactam), amikacin
      and gentamicin were statistically significantly higher for PER-1 positive strains
      than PER-1 negative ones. Resistance rates to ceftazidime, cefepime, aztreonam,
      piperacillin and ticarcillin-clavulanic acid in PER-1 positive isolates versus
      negative ones were as 82.3% vs. 29.2% (p< 0.01), 75.8% vs. 25% (p< 0.01), 83.9%
      vs. 30.4% (p< 0.01), 73.8% vs. 52.2% (p< 0.05), 85.5% vs. 66.7% (p< 0.05),
      respectively. Considering resistance rates to piperacillin-tazobactam and
      ciprofloxacin, PER-1 positive isolates versus negatives were 35.5% vs. 31.3%, and
      19.4% vs. 29.2%, respectively, revealing no statistical significance (p> 0.05).
      As a result, PER-1 type ESBL frequency and beta- lactam and aminoglycoside
      resistance rates were found remarkably high in nosocomial P.aeruginosa strains
      isolated in our hospital. It was concluded that antibiotic resistance should be
      continously monitorized and necessary measures to prevent further increase in
      resistance should be promptly established.

PMID- 22399166
TI  - [Investigation of plasmid-mediated quinolone resistance in Escherichia coli
      strains].
AB  - Quinolones are widely used antimicrobial agents, particularly for the treatment
      of infections caused by gram-negative bacilli such as E.coli. As a consequence,
      quinolone resistance has been increasing among this species in recent years.
      Bacterial resistance to quinolones usually results from mutations in the
      chromosomal genes which encode topoisomerases and also the expression of efflux
      pumps and loss of porines contributed to development of quinolone resistance.
      However, recent studies have shown that the spread and increase of quinolone
      resistance may be due to the transfer of plasmid-mediated genes. To date, three
      groups of plasmid-mediated quinolone resistance genes, namely qnr, aac(6')-Ib-cr,
      and qepA, have been described. The aim of this study was to investigate the
      presence of plasmid-mediated quinolone resistance genes in E.coli clinical
      isolates. A total of 112 quinolone-resistant E.coli strains isolated from
      different clinical specimens (84 urine, 16 blood, 10 wound, 2 bronchoalveolar
      lavage) of which 78 (69.6%) were extended-spectrum beta-lactamase (ESBL)
      positive, in Afyon Kocatepe University Hospital, Microbiology Laboratory were
      included in the study. In the isolates, qnrA, qnrB, qnrS, qnrC, qepA, and aac(6')
      1b-cr plasmid genes were analysed by polymerase chain reaction (PCR). After
      aac(6')- 1b determinant was amplified by PCR, all aac(6')-1b positive amplicons
      were analyzed by digestion with BseGI restriction enzyme to identify aac(6')-1b
      cr variant. It was found that, none of the strains horboured qnrA, qnrB, qnrS,
      qnrC and qepA genes, however, plasmid-mediated quinolone resistance gene aac(6')
      1b-cr was found positive in 59.8% (67/112) of the strains. It was notable that
      86.6% (58/67) of those isolates were ESBL producers. The rates of quinolone
      resistance among E.coli isolates infections were high in our region and an
      increasing trend has been observed in recent years. Our data indicated that the
      presence of plasmid- mediated resistance genes such as aac(6')-1b-cr, might have
      contributed to the high quinolone resistance rates. In conclusion, not only qnr
      genes but all other plasmid-mediated quinolone resistance genes, should be tested
      for the detection of plasmid-mediated quinolone resistance and this fact should
      be taken into consideration when the reservoirs are being searched for.

PMID- 22399167
TI  - [Evaluation of the ChromID ESBL agar for the detection of ESBL-positive
      Enterobacteriaceae and vancomycin-resistant enterococcus isolates from urine
      cultures].
AB  - Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae strains are
      frequent causative agents both in community-acquired infections and in nosocomial
      infections. The newly developed ChromID ESBL agar (bioMerieux, Marcy I'Etoile,
      France) is a chromogenic medium that helps rapid identification of ESBL-positive
      Enterobacteriaceae species from the clinical samples. The aim of this study was
      to evaluate the performance of ChromID ESBL agar in the rapid identification of
      ESBL-positive pathogens from the urine samples of the patients with urinary tract
      infections. A total of 672 urine samples (437 outpatients, 235 inpatients) were
      included in the study. All of the samples were inoculated simultaneously to 5%
      sheep blood agar, McConkey agar and ChromID ESBL agar media, and evaluated after
      incubation at 37 degrees C for 18-24 hours. Gram-negative pathogens were tested
      for ESBL both by the standard combined double-disk diffusion (CDD) method using
      ceftazidime and cefotaxime disks and by doubledisk synergy (DDS) test. Among 672
      urine cultures, 199 yielded microbial growth in routine media (sheep blood agar
      and/or McConkey agar), whereas 57 yielded bacterial growth in ChromID ESBL agar.
      When CDD method was accepted as the reference method according to Clinical and
      Laboratory Standards Institute (CLSI) recommendations, the sensitivity,
      specificity, positive and negative predictive values for ChromID ESBL agar for
      the detection of ESBL-positive bacteria in urinary tract infections were
      estimated as 97%, 92.9%, 89.1%, and 98.1%, respectively. Additionally, we also
      discovered that Chrom ID ESBL agar could detect vancomycin-resistant enterococci
      (VRE) as well as ESBL-positive bacteria, in our study. In order to investigate
      this observation we inoculated a total of 203 stock strains of Enterococcus spp.
      (118 vancomycin-sensitive, 85 vancomycin-resistant) to this medium. None of the
      vancomycinsensitive Enterococcus spp. did grow in ChromID ESBL medium, while 83
      of the 85 resistant isolates (97.6%) did grow in the medium. As a result, it was
      concluded that ChromID ESBL agar medium was advantageous since it led to the
      growth of VRE and ESBL-positive Enterobacteriaceae isolates in different colors
      and helped in early identification of these two problematic bacteria. We thought
      that especially early detection of VRE will accelerate the establishment of
      necessary measures to prevent the nosocomial spread of this microorganism.

PMID- 22399168
TI  - [Tuberculosis incidence and primary drug resistance rates in young soldiers: data
      from 14 military hospitals in Turkey].
AB  - Tuberculosis is an important health care problem worldwide as well as in Turkey
      and the control programmes are still in progress. Epidemiological data are
      necessary to conduct control studies related to the disease. Tuberculosis
      incidence and drug resistance rates are two necessary parameters which should be
      monitored for the effective establishment of tuberculosis control. In this
      objective, tuberculosis incidence and drug resistance rates were studied in young
      subjects performing their compulsory military service in Turkish Armed Forces.
      The study was performed in 14 military hospitals which served for the country
      wide soldier patients. Based on the computerized medical database of these
      military hospitals, conscripts diagnosed with tuberculosis between January 01,
      2009 and December 31, 2009 were retrospectively evaluated. Drug sensitivity tests
      of the Mycobacterium tuberculosis complex isolates were done prior to the
      treatment in the two military medical training hospitals of the two big cities of
      Turkey (Ankara and Istanbul). There were a total of 259 new tuberculosis cases in
      2009 and they were all male with a mean age of 22.51 +/- 4.63 years. The number
      of patients with pulmonary, extrapulmonary (pleuresia, lymphadenitis, others) and
      both pulmonary and extrapulmonary involvements were 175 (67.5%), 72 (27.8%) and
      12 (4.6%), respectively. The total rate of pulmonary tuberculosis cases was 72.2%
      (187/259) and 64.7% (121/187) of them were smear positive. Since the number of
      soldiers in Turkish army in the midyear was 537.200; total tuberculosis,
      pulmonary tuberculosis and smear-positive pulmonary tuberculosis incidences were
      estimated as 48.2/100.000, 34.8/100.000 and 22.5/100.000, respectively. Drug
      sensitivity tests was performed for the M.tuberculosis complex strains isolated
      from 104 cases. Primary resistance rate to at least one drug was detected as
      16.3% (n= 17), while the rates of resistance for isoniazid, rifampicin,
      ethambutol and streptomycin were 12.5% (n= 13), 7.7% (n= 8), 5.8% (n= 6) and 0.9%
      (n= 1), respectively. Multidrug resistant tuberculosis (isoniazid + rifampicin
      resistance) was detected in 6 (5.8%) patients. Our data indicated that although
      tuberculosis incidence among young soldiers was moderately high, a decreasing
      trend was observed when compared to the previous years. However, the rates of
      primary anti-tuberculosis drug resistance and multi-drug resistance were found to
      be high in our study. To decrease the incidence of tuberculosis and multidrug
      resistant tuberculosis, drug sensitivity tests should be performed for each
      patient and national tuberculosis programme should be established effectively.

PMID- 22399169
TI  - [Comparison and evaluation of Lowenstein-Jensen medium and 2% Ogawa medium for
      the diagnosis of tuberculosis].
AB  - Accurate diagnosis of tuberculosis is based on the detection of the bacilli in
      the clinical specimen. The growth of mycobacteria in laboratory media is regarded
      as the gold standard for diagnosis and use of two different cultivation media,
      one of them being a liquid one, is recommended. In this study, the diagnostic
      values of egg-based Lowenstein-Jensen (LJ) medium used extensively all over the
      world and Ogawa (2%) medium were compared. A total of 7912 pulmonary and
      extrapulmonary clinical samples which belonged to 3311 patients with suspected
      tuberculosis, were enrolled in the National Tuberculosis Reference Laboratory in
      Refik Saydam National Public Health Agency during 2.5 years (January 2006- June
      2008). The samples were processed by modified Petroff method (4% NaOH) for
      homogenization-decontamination-concentration on the same day and inoculated on
      two Ogawa and two LJ media. The cultures were incubated at 35-37 degrees C for
      eight weeks and were controlled on the third day of incubation in terms of
      contamination. If no contamination were detected, the cultures were incubated for
      a total of eight weeks with regular weekly controls. The colonies detected in
      culture media were identified by biochemical tests, including paranitrobenzoic
      acid (PNB), niacin accumulation and nitrate reduction tests. Those identified as
      Mycobacterium tuberculosis complex were reported as positive. The rates of
      contamination was 3.1% for Ogawa medium and 4% for LJ medium. Culture results
      were found positive for 248 patients (7.5%). While 210 of these were positive by
      both of the media, 20 (8.1%) patients were detected positive only by LJ and 18
      (7.3%) only by Ogawa medium. The sensitivity of LJ medium was 92.7% (230/248) and
      of Ogawa medium was 91.9% (228/248). When LJ medium was taken as the reference
      method, the sensitivity, specificity, positive and negative predictive values of
      Ogawa medium were 91.3%, 99.4%, 92.1% and 99.4%, respectively. It was concluded
      that, when low price and low contamination rates were taken into consideration,
      Ogawa medium, used together with a liquid medium + LJ medium, would increase the
      yield of mycobacteria from single samples (cerebrospinal fluid, biopsy, pus,
      etc.) sent to the laboratories.

PMID- 22399170
TI  - [Anti-candidal activity of clinical Pseudomonas aeruginosa strains and in vitro
      inhibition of Candida biofilm formation].
AB  - It has been shown recently that signal-mediated interactions between the
      opportunistic pathogens Pseudomonas aeruginosa and Candida albicans affect
      virulence features in both organisms. It has been emphasized that the anti
      candidal activity of P.aeruginosa is especially due to its pyocyanin pigment. The
      structure and the properties of monospecies biofilms and their role in infectious
      disease have been extensively studied. However, there are only few studies on
      interactions between P.aeruginosa ve Candida spp. In mixed biofilms. Therefore,
      in this study, the investigation of anti-candidal activity of P.aeruginosa
      against Candida spp. And the effect on C.albicans biofilm were aimed. A total of
      58 P.aeruginosa strains isolated from several clinical specimens and one of each
      C.albicans ATCC 90028, C.parapsilosis ATCC 22019, C.glabrata ATCC 90030 and a
      C.tropicalis clinical isolate were included in the study. The anti-candidal
      activity of P.aeruginosa strains were investigated on Sabouraud dextrose agar
      using Kerr's method. The absence of the growth of Candida strains were evaluated
      as total inhibition. The effect of two P.aeruginosa strains showing total
      inhibition and one isolate without inhibition effect on C.albicans biofilm was
      investigated by microplate method. For the evaluation of monospecies or mixed
      species biofilms of Pseudomonas and C.albicans, the number of colony forming
      units (cfu/ml) after 90 minutes (adhesion phase), 24 hours and 48 hours (biofilm
      phase) incubation were determined. Then, cfu numbers of monospecies and mixed
      species of Pseudomonas and C.albicans were compared. Total inhibition rates of
      Pseudomonas strains against C.albicans, C.tropicalis, C.glabrata and
      C.parapsilosis were determined as 63.8%, 75.9%, 65.5% and 72.4%, respectively. A
      significant reduction was determined in cfu/ml numbers of mixed species of
      Pseudomonas and C.albicans compared to cfu numbers in monospecies biofilm after
      90 minutes, 24 hours and 48 hours (p< 0.05). In addition to the inhibitory effect
      of P.aeruginosa on Candida growth, in a dual species environment both organisms
      mutually suppressed each others' biofilm development quantitatively. These
      findings indicated that molecular basis of signal-mediated interaction between
      Pseudomonas and Candida spp. Should be clarified for better understanding of the
      pathogenesis of mixed bacterial-fungal infections.

PMID- 22399171
TI  - [Evaluation of serological status of children following hepatitis B vaccination
      during infancy].
AB  - The aims of this study were to determine anti-HBs positivity in children who had
      received three doses of hepatitis B vaccine during infancy and to evaluate the
      factors that may affect the serological status. Local ethics committee approval
      was obtained at the beginning of the study. The study was carried out between
      December 2005 and October 2007 among children attending the outpatient clinics of
      medical school hospital. The study encompassed 912 children (393 female, 519
      male; aged 1-5 years old) who had been immunized with three doses of
      intramuscular recombinant hepatitis B vaccine during infancy. All of the children
      were born to HBsAg negative mothers and did not have any known immune system
      problems. Sociodemographic characteristics and passive smoking status were
      gathered by a questionnaire. Anthropometric measurements were taken, and a
      detailed physical examination was carried out for each child. Blood samples were
      obtained to check serum HBsAg, anti-HBs and anti-HBc levels by commercial micro
      ELISA (Sanofi Diagnostics Pasteur, Sydney) method. Levels of anti-HBs >= 10
      mIU/ml were defined as seropositivity. In seronegative children, anti-HBs levels
      were re-checked 4 weeks after receiving one booster dose of hepatitis B vaccine.
      Of the children 877 (96.2%) were found anti-HBs positive, while all of them were
      negative for anti-HBc or HBsAg. Of children 34.8% were 12-23 months; 28.7% were
      24-36 months; and 36.5% were 37-60 months-old, and anti-HBs negativity rate was
      higher in the older age group with a statistically significant difference (1.4%,
      3.9% and 4.2%, respectively; p= 0.003). Anti-HBs antibodies were found negative
      in 2.8% of children who were born by vaginal route and in 5.8% of children who
      were born by cesarean section, the difference being statistically significant (p=
      0.016). There were no significant differences between anti-HBs seropositivity and
      gender, working/ educational status of the mothers and the presence of smoking
      parents in the family (p> 0.05). Logistic regression analysis indicated that the
      factors that affect antibody levels in vaccinated children were the duration of
      breastfeeding only (4.77 +/- 1.53 months in anti-HBs positives and 3.69 +/- 2.13
      months in negatives; p= 0.008), birth weight (3328.18 +/- 318 g in anti-HBs
      positives and 3135.27 +/- 488 g in negatives; p= 0.037) and pregnancy parity
      (anti-HBs was negative in 3.4% of children born from mothers who had < 2
      parities, and 8.2% of children born from mothers who had < 3 parities; p= 0.037).
      The remaining 35 (3.8%) children with undetectable antibody levels became
      seropositive after one dose of hepatitis B vaccination, with the antibody levels
      of >= 100 mIU/ml. This response underlined the presence of immune memory in
      vaccinated children. The results of this study indicated that almost all 1-5
      years old children who had received three doses of hepatitis B vaccine during
      infancy were protected from hepatitis B virus infection. It was concluded that
      similar studies should be carried out in different settings.

PMID- 22399172
TI  - [Attitudes and side effects related to pandemic influenza A (H1N1) vaccination in
      healthcare personnel].
AB  - The aims of this study were to evaluate the attitudes towards H1N1 vaccination
      and to determine the safety and side effects following 2009 pandemic influenza A
      (H1N1) vaccination. Pandemic influenza vaccine had been administered to the
      healthcare personnel in our research and training hospital in December 2009. The
      rate being vaccinated was established as 40% (800/2000). Four months following
      vaccination, the opinions about vaccination were asked to the healthcare workers,
      and also side effects were questioned to the vaccinated group. Two different
      questionnaires (for vaccinated and unvaccinated subjects) were delivered to the
      volunteers who agreed to participate in the study. Demographic features, reasons
      related to being vaccinated or not, were questioned. The vaccinated group was
      also questioned for the presence of chronic diseases, previous vaccinations
      (pandemic/seasonal influenza), local or systemic reactions that develop after
      vaccination. A total of 332 volunteers participated in the questionnaire. Of them
      247 (74.4%) were vaccinated and 85 (25.6%) were unvaccinated. Male/female ratio
      of the participants was 1.2, and 55.7% of them were older than 30-year-old. Most
      of the participants (82.8%) were highly educated (high school and faculty
      graduated). Vaccination rates were found statistically significant in advanced
      age group compared to young adults (p= 0.042); in male gender compared to females
      (p= 0.001) and in parents compared to subjects who didn't have children (p=
      0.021). Vaccination rates were observed to be higher (57.5%) in non-medical staff
      (cleaning employers, administrative personnel, etc.) than the physicians (29.1%)
      and nurses (13.4%), and the rate was also high (54.7%) in personnel who worked in
      intensive care units, emergency department and administrative units than the
      personnel who worked in the clinics of internal medicine (22.3%) and surgery
      (23.1%) (p= 0.001). The most important causes of rejecting vaccination were being
      afraid of the side effects (69.4%) and not believing the effectiveness of the
      vaccine (56.4%). The leading causes of accepting vaccination were worries about
      infecting their family (60.3%) and being in a risk group (54.3%). After
      vaccination, local reactions (pain, swelling and redness at the vaccination site)
      were described in 43.3% and systemic reactions (weakness, fatigue, muscle aches,
      influenza-like symptoms, etc.) were described in 43.7% of the subjects. Severe
      side effects such as vasculitis, neuritis, encephalomyelitis, Guillian-Barre
      syndrome and anaphylactic reaction were not observed in any of the vaccinated
      cases. It was detected that worries about the safety of vaccine had negative
      impact for vaccination. Since no serious side effects were detected related to
      vaccination, it was concluded that the vaccine was safe. In spite of the
      scientific proofs, negative concerns about the safety of the vaccines can
      unfavorably affect the vaccination campaigns and can jeopardize efforts of
      influenza control. As a result, data collection systems about the safety and side
      effects of the vaccine all over the country and regular reports about these data
      may more efficiently guide vaccination programs in the future.

PMID- 22399173
TI  - [Identification of filamentous fungi isolated from clinical samples by two
      different methods and their susceptibility results].
AB  - Molds are widely distributed in nature. Aspergillus spp. represent the most
      frequently observed causative agents, however less frequent pathogens Fusarium,
      Scedosporium and Zygomycetes have also been considered the most important causes
      of morbidity and mortality in profoundly immunosuppressed hosts. The aims of this
      study were to identify filamentous fungi isolated from clinical specimens by
      conventional and molecular methods, and to detect their antifungal
      susceptibilities. A total of 6742 clinical specimens obtained from hospitalized
      patients at critical units of Mersin University Medical Faculty Hospital and sent
      to our laboratory between April 2008-January 2010 were included in the study. The
      isolates were identified by classical mycological methods and polymerase chain
      reaction-based DNA sequencing. Susceptibilities to fluconazole and voriconazole
      were tested by disk diffusion method and to fluconazole, voriconazole,
      amfoterisin B, caspofungin and posaconazole by E-test. Filamentous fungi were
      isolated from 71 (1.05%) samples (13 sputum, 4 wound, 4 peritoneal fluid, 3
      extrenal ear discharge, 3 abscess and one of each cerebrospinal fluid, blood,
      tissue biopsy, nasal swab and conjunctival swab) which belonged to 32 patients
      (13 female, 19 male; age range 7 months-77 years, mean age: 46.6 years). Of the
      patients 62.3% presented one or more risk factors such as chronic renal failure
      (n= 8), chronic obstructive lung disease (n= 6), malignancy (n= 6), diabetes
      mellitus (n= 5) and peripheral vascular disease (n= 5). Of the isolates six were
      identified as Aspergillus niger, six as Aspergillus flavus, five as Aspergillus
      fumigatus, four as Aspergillus terreus, five as Fusarium spp., two as Bipolaris
      spp., and one of each as Acremonium spp., Aurebasidium spp., Mucor spp., and
      Scedosporium spp. By conventional methods. Three isolates exhibited different
      identities by DNA sequencing. All Aspergillus isolates were correctly identified
      at species level by both methods, Other fungi were identified at genus level by
      conventional methods and at species level by DNA sequencing. Fluconazole minimum
      inhibitory concentration (MIC) values were determined as > 256 mg/L in all
      strains, except Scedosporium; voriconazole MIC values were < 0.38 mg/L in all
      Aspergillus spp. Caspofungin MIC values were > 32 mg/L for Fusarium,
      Scedosporium, Rhizopus and Bipolaris strains and <= 0.006-0.125 mg/L in all
      Aspergillus isolates, In three strains (Fusarium equiseti, Cylindrocarpon
      lichenicola and Rhizopus oryzae) posaconazole minimum inhibitory concentration
      (MIC) values were > 32 mg/L, however it was < 1.5 mg/L, for the other strains.
      Amphotericin B MIC values were > 32 mg/L for Fusarium, Scedosporium, Rhizopus and
      all A.terreus strains and < 2 mg/L for the others. E-test and disk diffusion test
      results were compatible with each other for all the antifungal agents tested. In
      conclusion, the identification of filamentous fungi such as Aspergillus and
      Fusarium spp. is easily and reliably achieved by conventional methods. Since the
      rate of invasive fungal infections is increasing currently, filamentous molds
      should be searched especially in the clinical specimens of immunocompromised
      patients for accurate and prompt diagnosis of such infections and to decrease the
      related mortality risk.

PMID- 22399174
TI  - [Agents of otomycosis in Manisa region, Turkey, 1995-2011].
AB  - Otomycosis, which is otitis externa caused by fungi, is common throughout the
      world especially in tropical and subtropical countries. However, the
      epidemiologic data about the etiologic agents of otomycosis in Turkey is limited.
      The aim of this retrospective study was to evaluate the agents of otomycosis in
      patients living at Manisa region (located at western Anatolia of Turkey). A total
      of 2279 cases [1465 male, 813 female; age range 1-87 (mean: 41.7) years] who were
      clinically prediagnosed as otomycosis at Celal Bayar University Hospital, between
      February 1995 and July 2011, were included in the study. External ear swab
      samples from patients with suspicion of otomycosis have been evaluated by routine
      mycological methods. Identification of mold-like fungi was based on colony
      morphology and microscopic examination of fungal structure, whereas germ tube
      test, growth characteristics on cornmeal-Tween 80 agar and API 20C AUX (bio
      Merieux, France) system were used for the identification of yeast-like fungi. Of
      the samples, 28% (638/2279) were found positive by direct microscopy and 24%
      (544/2279) by culture methods. Among culture-positive cases the isolation rates
      of mold-like and yeast-like fungi were 66% (359/544) and 34% (185/544),
      respectively. The number of distribution of the molds were as follows;
      Aspergillus niger (180), Aspergillus fumigatus (95), Aspergillus terreus (32),
      Aspergillus flavus (23), Aspergillus spp. (14), Penicillium spp. (13),
      Trichophyton spp. (T.rubrum 1, T.mentagrophytes 1); while this distribution was
      as follows for the yeasts; Candida tropicalis (97), Candida albicans (39),
      Candida parapsilosis (21), Candida glabrata (19), Candida kefyr (4),
      C.guilliermondii (2), Candida krusei (1), Geotrichum candidum (1) and
      Trichosporon capitatum (1). It was notable that 96% (344/359) of mold-like fungi
      were Aspergillus spp., and 99% (183/185) of yeast-like fungi were Candida spp.
      The results of this study indicated that the most frequent agents of otomycosis
      were non-dermatophyte species such as Aspergillus, followed by Candida.
      Dermatophytes were isolated in a small number of otomycosis cases. These data
      will provide support to the establishment of antifungal therapy guidelines for
      otomycosis.

PMID- 22399175
TI  - [Investigation of Microsporidia prevalence by different staining methods in cases
      of diarrhea].
AB  - Microsporidia, depending on their different species, generally lead to self
      limited, sporadic and mild infections such as diarrhea, corneal ulcer and
      myositis. They are considered as opportunistic pathogens in HIV-positive patients
      however in recent years Microsporidia have been detected also in immunocompetent
      individuals as a cause of diarrhea. Diagnosis of Microsporidia depends on the
      detection of spores or different developmental stages of protozoon in stool,
      urine, sinus aspirates, nasal discharge, bronchoalveolar lavage or tissue
      biopsies. Diagnosis of Microsporidia infections is usually achieved by the use of
      different staining methods, serological tests, polymerase chain reaction, and
      electron microscopic methods. The aims of this study were to detect the incidence
      of microsporidia in patients with diarrhea by using three different staining
      methods and to compare the performance of these methods. A total of 225 stool
      samples from diarrheal patients (84 were children, 141 were adults; 103 were
      female, 122 were male) admitted to Gazi University Medical Faculty Hospital
      between March-June 2009, have been evaluated in the laboratory of Medical
      Microbiology Department. Stool samples were examined in terms of the presence of
      Microsporidia spores by Weber's modified trichrom staining (MTS), calcofluor (CF)
      and acridine orange (AO) staining methods. Microsporidia positivity rate was 9.8%
      (22/225) in the diarrheal patients, the rate being 9.5% (8/84) in children and
      9.9% (14/141) in adults. There was no statistically significant difference
      between age and gender groups (p> 0.05) regarding Microsporidia detection. When
      MTS was considered as the reference method, sensitivity, specifity and
      consistency of AO staining were estimated as 100%, 91.6% and 92%, respectively,
      while those rates for CF staining were 95.4%, 99.5% and 99%, respectively. There
      was very strong and significant correlation (r= 0.950, p< 0.001) between CF
      staining and MTS, while there was strong and significant (r= 0.719, p< 0.001)
      correlation between AO staining and MTS. Although AO staining is rapid and
      convenient, the positive predictive value was measured very low (56.4%) and the
      interpretation of stained slides was very difficult since background of the
      slides was stained orange and there were a lot of dye artefacts. In conclusion,
      screening Microsporidia in all diarrheal stool samples is of diagnostic value. To
      increase sensitivity and reliability in the detection of Microsporidia spores in
      diarrheal samples, initial application of calcofluor staining should be followed
      by the confirmatory MTS method.

PMID- 22399176
TI  - [Investigation of the presence of Cryptosporidium spp. in different water sources
      in Mersin province, Turkey].
AB  - Cryptosporidium is an intracellular protozoon that causes enteritis in human and
      animals. Contaminated water and food are the major sources for the transmission
      of oocysts via oral-fecal route. It is reported that the prevalence of
      cryptosporidiosis is higher in developing countries than developed countries
      because of inefficient sanitation and disinfection facilities for drinking water.
      The most frequently detected species is Cryptosporidium parvum leading to high
      morbidity in healthy subjects and also fatal infections in immunocompromised
      patients. The acid-fast staining method is widely used in the diagnosis of
      cryptosporidiosis. Nowadays, Cryptosporidium could easily be detected in water
      supplies and asymptomatic carriers by molecular techniques to obtain
      epidemiological data. In this study it was aimed to detect and identify
      Cryptosporidium oocysts in different water sources in Mersin province, Turkey. A
      total of 135 water samples (70 taps, 50 wells and 15 sewage) collected from city
      center (n= 25) and from Tarsus (n= 32), Mezitli (n= 33) and Karaduvar (n= 45)
      counties between March 2007 and May 2009 were included in the study. Water
      samples in 10 liter volumes, were filtered by 0.45 um pore-sized membrane filter
      vacuum/ pressure pumping technique. Cryptosporidium oocysts in filtrates were
      detected by modified cold Kinyoun acid-fast stain (MCK) technique and also
      identified and typed by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) method. MCK yielded three and PCR yielded seven positive
      results. All the strains were identified as C.parvum by PCR-RFLP method. All of
      the three MCK-positive samples were also found positive with PCR, however four
      PCR positive samples were MCK-negative. Thus, the prevalence of C.parvum was
      estimated as 5.2% (7/135) in our region. Of seven positive samples, one was a
      sewage water sample collected from the city center, while the remaining (two tap
      water, two well water and two sewage water samples) belonged to the samples
      collected from Karaduvar county, interestingly. It was thought that deficient
      infrastructure and use of well water as drinking water supply in Karaduvar region
      might be the cause of high rate of Cryptosporidium (6/45; 13.3%). Further studies
      which will determine the genotypes and investigate the phylogenetic relationship
      between these Cryptosporidium spp., might aid to the epidemiology of
      cryptosporidiosis in our region.

PMID- 22399177
TI  - [Investigation of a nosocomial outbreak caused by ESBL positive Klebsiella
      pneumoniae in neonatal intensive care unit by AP-PCR].
AB  - In the present study, we describe an outbreak caused by extended-spectrum beta
      lactamase (ESBL) producing Klebsiella pneumoniae in the neonatal intensive care
      unit (NICU) of a tertiary-care hospital. Nosocomial blood-stream infections were
      detected in three patients hospitalized in NICU. Two of the cases were
      transferred to NICU due to premature birth and the other due to the presence of
      cleft palate and retrognathia. K.pneumoniae was isolated on the 5th day of
      hospitalization of the first patient from umbilical swab and blood culture; on
      the 15th day of hospitalization of the second patient from blood culture and on
      the 7th day of hospitalization of the third patient from blood culture. The
      isolates were identified by automated API Rapid ID 32 Staph (BioMerieux, France)
      system in addition to conventional laboratory methods. Antibiotic
      susceptibilities of the isolates were determined by using Kirby-Bauer disk
      diffusion method according to Clinical and Laboratory Standards Institute (CLSI)
      criteria. The same antibiotic susceptibility patterns were detected in all
      isolates. Active surveillance cultures included environmental sampling from
      surfaces of NICU, laryngoscopes, ventilators and connections of ventilators,
      stethoscopes, nebulizers, aspiration tubings, disinfectant solutions, couveuse
      and couveuse distilled water. Two ESBL producing K.pneumoniae strains, presenting
      the same antibiotic susceptibility pattern with the clinical strains, were
      isolated from one couveuse distilled water sample and one aspiration tubing. All
      of the K.pneumoniae isolates were resistant to amoxycillin-clavulonic acid,
      cefazolin, cefepime, ceftriaxone, ceftazidime, cefuroxime, aztreonam and
      trimetoprim-sulphametoxazole and susceptible to cefoxitin, imipenem, meropenem,
      gentamicin, tobramycin, amikacin, netilmisin, tetracycline, ciprofloxacin and
      chloramphenicol. Arbitrarily primed polymerase chain reaction (AP-PCR) analysis
      done with M13 primer revealed the same genotype for the patient and environmental
      K.pneumoniae isolates. It was concluded that AP-PCR which is a simple, rapid and
      cheap method for the determination of genetic relatedness between isolates, can
      be applied for the detailed evaluation of nosocomial outbreaks to detect the
      source of infection and control the dissemination of the outbreak.

PMID- 22399178
TI  - [Prevalence and risk factors for methicillin-resistant Staphylococcus aureus
      colonization among outpatients undergoing hemodialysis treatment].
AB  - Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) is
      frequent among hemodialysis patients and lead to increased morbidity and
      mortality rates. It is known that nasal colonization plays an important role for
      the development of MRSA infections. The aim of this study was to determine the
      prevalence and risk factors for MRSA colonization among outpatients undergoing
      hemodialysis. A total of 466 adult patients (199 female, 267 male; age range: 18
      89 years, mean age: 55.8 +/- 15.1 years) who were under hemodialysis between
      September-December 2008 in different health centers at Pamukkale/ Denizli region,
      Turkey, were included in the study. Swab samples obtained from anterior nares of
      patients were cultivated on sheep-blood agar and mannitol-salt agar media. The
      isolates were identified by conventional bacteriological methods. S.aureus
      strains were isolated from 204 (43.8%) patients and 34 (16.7%) were found
      methicillin-resistant. Thus the rate of MRSA colonization in hemodialysis
      patients was detected as 7.3% (34/466). All of the MRSA strains were found
      susceptible to vancomycin, linezolid and tigecycline, while the resistance rates
      for the other antimicrobial agents were as follows: 70.6% to azithromycin and
      claritromycin; 64.7% to erythromycin; %58.8 to clindamycin, gentamicin and
      trimethoprim-sulfamethoxazole; 55.9% to ciprofloxacin; 44.1% to tetracycline and
      rifampin; 5.9% to chloramphenicol. Inducible clindamycin resistance in MRSA
      isolates was %23.5 (8/34), and multidrug resistance rate was 76.5% (26/34).
      Multivariate analysis revealed that the history of previous hospitalization
      within a year [odds ratio (OR), 3.426; 95% confidence interval (CI), 1.595-7.361,
      p= 0.002] and the presence of chronic obstructive lung disease (OR, 5.181; 95%
      CI, 1.612-16.648, p= 0.006) were independent risk factors for MRSA colonization
      in this population. A better understanding of the prevalence and risk factors for
      nasal MRSA colonization among hemodialysis population may hold significant
      implications for both the treatment strategies and prevention of MRSA infections
      to establish appropriate infection control measures.

PMID- 22399179
TI  - [Septic arthritis of hip due to Salmonella Typhi in a patient with multiple
      sclerosis].
AB  - The most common microorganisms isolated from septic arthritis are Staphylococcus
      aureus and streptoccocci. Septic arthritis due to Salmonella spp. are rare and
      the most commonly isolated species are S.Choleraesuis and S.Typhimurium. However
      the number of septic arthritis cases due to S.Typhi is low in literature. In this
      report, septic arthritis of hip due to S.Typhi in a multiple sclerosis patient
      who was under steroid therapy, was presented. A 25-year-old female patient was
      admitted to our clinic with the complaints of fever, left hip pain, standing and
      walking disability for 10 days. Her anamnesis revealed that she had had a
      multiple sclerosis attack and underwent triple pulse steroid therapy. Laboratory
      findings were as follows; WBC count: 16.300/mm3 (70% polymorphonuclear
      leukocyte), hemoglobin: 10.6 g/dl, erythrocyte sedimentation rate: 140 mm/hour,
      CRP: 28.7 g/L, AST: 86 U/L and ALT: 77 U/L. In lumbosacral magnetic resonance
      imaging, trochanteric bursitis and generalized myositis were detected in left hip
      joint compatible with septic arthritis. S.Typhi was isolated from patient's blood
      and operational tissue samples. Serum Salmonella TO and TH titers were found as
      1/400 and 1/200, respectively. Antibiotic susceptibility test was performed by
      disk diffusion method, and the isolate was found susceptible to ampicillin,
      chloramphenicol, ceftriaxone, ciprofloxacin and trimethoprim-sulphametoxazole.
      The patient was treated by surgery and also by two weeks parenteral (2 x 400 mg)
      and 6 weeks oral (2 x 500 mg) ciprofloxacin treatment. Six months follow-up of
      the patient revealed that clinical, radiological and laboratory findings were
      normal. As far as the national literature was considered, this was the first
      S.Typhi septic arthritis case involving the hip joint and demonstrating bacterial
      growth both in blood and operational tissue. The presentation of the infection as
      arthritis plus diffuse myositis and bursitis, is also noteworthy.

PMID- 22399181
TI  - [An imported Chikungunya fever case from New Delhi, India to Ankara, Turkey: the
      first imported case of Turkey and review of the literature].
AB  - Chikungunya virus (CHIKV) is an arthropod-borne alphavirus that causes an acute
      febrile illness, chikungunya fever. CHIKV virus is geographically distributed in
      Africa, India, and South-East Asia. Chikungunya fever outbreaks have been
      reported from India since 2006. The incubation period is 3-7 days, and the
      disease is characterized by sudden onset of high fever and severe arthralgia.
      Other symptoms can be rash, headache, fatigue, nausea-vomiting, and myalgias.
      Here, we report the first Chikungunya case imported from India, New-Delhi to
      Ankara, Turkey. In December 2010, a 55-year-old female Turkish government
      employee living in urban area of New Delhi for the last 3 years had sudden onset
      fever up to 38.4 degrees C for 2 days. Itching rash and arthralgia also
      developed. Symptomatic treatment was given to patient in New Delhi. She returned
      to Turkey and was admitted to Hacettepe University Medical Faculty, Department of
      Internal Medicine, Infectious Diseases Unit, since arthralgia has continued on
      the 26th day of her complaints. Hepatomegaly and tenosynovitis were detected in
      her physical examination. Serum sample sent to Refik Saydam National Public
      Health Agency, Virology Reference and Research Laboratory, yielded negative
      results for specific IgM and IgG antibodies against Hantavirus and Dengue virus
      types 1-4; however, the results were positive for CHIKV specific IgM and IgG
      antibodies by commercial immunofluorescence method (Euroimmun, Germany). CHIKV
      RNA which was searched by in-house real-time RT-PCR was negative. The second
      serum sample obtained three weeks later also found positive for CHIKV specific
      IgM and IgG antibodies. This was the first laboratory confirmed imported
      Chikungunya case in Turkey. There are predictions regarding the presence of Aedes
      species mosquitos that can transmit this virus in Turkey. This case report will
      be an alarming signal for the clinicians in our country to consider Chikungunya
      fever in the differential diagnosis of patients presenting with fever, arthralgia
      and rash.

PMID- 22399180
TI  - [A rare cause of pneumonia: Shewanella putrefaciens].
AB  - Shewanella putrefaciens is a gram-negative, non-fermentative, oxidase positive,
      motile bacillus that produces hydrogen sulphide. It is found widely in the nature
      especially in marine environments. Although it is accepted as saprophytic,
      different clinical syndromes, most commonly skin or soft tissue infections, have
      been associated with S.putrefaciens, mainly in immunocompromised cases and
      patients with underlying diseases. However, pneumonia cases due to S.putrefaciens
      are quite limited in the literature. In this report, a case of pneumonia caused
      by S.putrefaciens was presented. A 43-year-old female patient was admitted to our
      hospital with the complaints of fever, cough, sputum and weakness. The patient
      has had brochiectasis since childhood and has used periodical antibiotic
      therapies due to pneumoniae episodes. She was diagnosed to have pneumonia based
      on the clinical, radiological and laboratory findings, and empirical antibiotic
      treatment with ciprofloxacin and ceftazidime combination was initiated. Gram
      stained smear of sputum yielded abundant leucocytes and gram-negative bacteria,
      and the isolate grown in the sputum culture was identified as S.putrefaciens by
      conventional methods and API 20 NE (BioMerieux, France) system. The isolate was
      found susceptible to ceftriaxone, ceftazidime, cefepime, ciprofloxacin,
      piperacillin-tazobactam, cephoperazon-sulbactam, imipenem, amikacin, gentamicin
      and trimethoprime-sulphametoxazole; whereas resistant to ampicillin, amoxycillin
      clavulanate, cefazolin and cefuroxime, by Kirby-Bauer disk diffusion method.
      According to the antibiogram results, the therapy was changed to ceftriaxone (1 x
      2 g, intravenous). The patient was discharged with complete cure after 14 days of
      therapy. In conclusion, S.putrefaciens should be considered in patients with
      predisposing factors as an unusual cause of pneumonia and the characteristics
      such as H2S production and sensitivity to third generation cephalosporins and
      penicillins should be used to differentiate it from Pseudomonas aeruginosa and
      prevent the unnecessary use of antipseudomonal antibiotics.

PMID- 22399182
TI  - [A case of Crimean-Congo hemorrhagic fever with long incubation period in
      Kocaeli, Turkey].
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a viral hemorrhagic disease with high
      mortality rate. CCHF is endemic in Central Anatolia and East and Central Black
      Sea parts of Turkey, however sporadic cases have been detected in the other
      regions. The incubation period of the disease is between 1-3 days (maximum 12
      days). In this report, a very rare CCHF case with a long incubation period of 30
      days, was reported. A 40-year-old female patient living in a village of Kocaeli,
      Turkey was admitted to a health center in June 2010 with the complaints of
      headache, myalgia, nausea, vomiting, fatigue and fever. Since laboratory results
      revealed severe thrombocytopenia (18.300/mm3), the patient was referred to the
      university hospital in Kocaeli. It was learned from her history that she had been
      working in the garden and removed a tick from the skin of gluteal area a month
      ago without seeking any medical help. Physical examination of the patient
      revealed that her general condition was well, oriented and cooperative, body
      temperature was 36.6 degrees C, pulse 82/minute, trombocyte count 69.400/mm3 and
      liver enzymes were elevated (ALT: 194 U/L, AST: 499 U/L, GGT: 384 U/L, LDH: 1290
      U/L). Petecchial lesions were seen on hard palate and extremities and a hyperemic
      lesion was detected at the gluteal area where the tick had attached. In-house
      real-time polymerase chain reaction test for CCHF, performed at Refik Saydam
      National Public Health Agency, Virology Reference and Research Laboratory,
      revealed positive result. This case was presented to withdraw attention to a long
      incubation period CCHF and also of its epidemiological importance since it was
      the first case in Kocaeli province, Turkey.

PMID- 22399183
TI  - [Blastoschizomyces capitatus fungemia: three case reports and review of the
      literature].
AB  - Blastoschizomyces capitatus is a rare fungal pathogen that may lead to fatal
      infections especially in immunosuppressive individuals. In this report, three
      cases of B.capitatus were presented. The patients were under treatment for acute
      myeloid leukemia and their blood cultures yielded B.capitatus. The patients
      clinical conditions deteriorated and they died despite amphotericin B treatment.
      The isolates were identified by conventional mycological methods and API 20C AUX
      (Bio-Merieux, France) system. Antifungal susceptibility test of the strains was
      performed with Sensititre Yeast One Panel (Trek Diagnostic Systems, USA) and
      minimum inhibitory concentration (MIC) ranges for amphotericin B, caspofungin,
      fluconazole, itraconazole, voriconazole, posaconazole, and flucytosine were found
      as 0.5-1; > 16; 8-16; 0.5; 0.25; 0.5-1 and 0.06-0.25 ug/ml, respectively.
      Isolated strains were genotyped with RAPD-PCR (Random Amplified Polymorphic DNA
      Polymerase Chain Reaction) using Cnd-3, Cnd-4, OPE-03, OPE-18 primers. The
      strains isolated from the first two cases were found to be genotypically
      identical, while the strain isolated from the third case was different.
      Genotypically identical isolates belonged to two patients who were admitted to
      the hospital with approximately 18 months interval. The other strain with a
      unique genotype, was isolated from a patient who was admitted to the hospital
      about two years later than the other two patients. In conclusion, B.capitatus
      should be considered as an important opportunistic pathogen especially in
      patients with hematologic malignancies. The data of this study demonstrated that
      the lowest MIC values for B.capitatus strains were with voriconazole.

PMID- 22399184
TI  - [An overview of Toscana virus infections].
AB  - Toscana virus which is an arbovirus transmitted to humans by sandflies
      (Phlebotomus spp.), can cause febrile illness and meningitis mainly during
      summer. It has a tropism for central nervous system and is a major cause of
      meningitis and encephalitis in endemic countries. Majority of the clinical and
      epidemiologic studies on Toscana virus have been reported from Italy, France,
      Spain, Portugal and other Mediterranean countries. Although Toscana virus
      infections has been identified, data on virus activity in Turkey are limited. In
      this review article, the epidemiological, clinical and laboratory features of
      Toscana virus as a cause of febrile diseases, meningitis and encephalitis during
      summer in Turkey were discussed.

PMID- 22399185
TI  - [Tularemia: are hunters really a risk group?].
AB  - The aim of this study was to investigate the tularemia seroprevalence among
      hunters mainly hunting in districts with emerging tularemia cases in Yozgat
      province located at the Central Anatolia region of Turkey. A total of 64 serum
      samples were collected from the subjects (all were male; age range: 18-67 years;
      mean age: 42.7 years) registered to Hunting and Shooting Clubs in Yozgat province
      and it's two districts, during January-April 2010 and anamnestic data were
      obtained using a questionnaire. The presence of Francisella tularensis antibodies
      in serum samples were screened by microagglutination test (MAT), and the positive
      samples were also confirmed by a commercial ELISA kit (Serazym, Germany). Four
      (6.3%) out of 64 were found to be seropositive for tularemia with titers of 1/160
      in three cases, and 1/2560 in one case. All of the MAT positive samples yielded
      positive results with ELISA test and all seropositive cases had negative brucella
      agglutination result. No tularemia compatible clinical history were determined in
      two hunters with 1/160 antibody titer. However, one of the cases had defined
      symptoms consistent with oropharyngeal form. The hunter with 1/2560 antibody
      titer developed acute oropharyngeal tularemia and treated with 14 days of
      ciprofloxacin therapy. Evaluation of risk factors in seropositive cases revealed
      consumption of spring water as a risk factor. In conclusion, our results
      indicated a considerable exposure of hunters to F.tularensis in Yozgat province
      and reflected a high prevalence of the pathogen around Yozgat, which coincided
      with the high notification rate of tularemia in this region.

PMID- 22399186
TI  - [Investigation of Chlamydophila pneumoniae seropositivity and risk factors in
      patients with atherosclerotic vascular disease in Sivas, Turkey].
AB  - The role of various microorganisms including Chlamydophila (formerly Chlamydia)
      pneumoniae, have been frequently investigated in the pathogenesis of
      atherosclerosis. In our study, the relationship between C.pneumoniae
      seropositivity and risk factors for atherosclerosis have been evaluated. A total
      of 90 atherosclerotic patients (71 of them were male; age range: 45-87 years;
      mean age: 65.3 +/- 8.7 years) and 90 control subjects without coronary diseases
      (41 of them were male; age range: 42-84 years; mean age: 61.6 +/- 9.6 years) were
      included in the study. Both groups were also evaluated for the presence of risk
      factors such as age, gender, smoking, hypertension, diabetes, obesity,
      dyslipidemia, familial history and the high levels of ferritin, cholesterol
      (total, HDL and LDL) and HS (high sensitive)-CRP. The presence of C.pneumoniae
      IgG, IgM and IgA antibodies were investigated by micro-immunofluorescence (MIF)
      and ELISA methods using commercial kits (Euroimmun, Germany). The total antibody
      seropositivity rate was found 100% (90/90) in patient group by both MIF and ELISA
      methods, while this rate in control group was 94% (85/90) by MIF and 92% (83/90)
      by ELISA. When MIF test results were taken into consideration (since it is
      accepted as the reference method for C.pneumoniae serology), IgG, IgM and IgA
      positivity rates in patient and control groups were found as 100% (90/90) and 89%
      (80/90); 70% (63/90) and 59% (53/90); 3% (3/90) and 2% (2/90), respectively.
      Statistically significant difference between patient and control groups was
      detected only for IgG positivity (p< 0.05) and for total antibody positivities
      (100% and 94%, respectively) (p< 0.05). The evaluation of the risk factors
      revealed that age, hypertension, dyslipidemia and HS-CRP levels exhibited
      statistically significant differences between patient and control groups (p< 0.05
      for each parameter tested). Statistically significant relation was detected only
      between high HS-CRP levels and C.pneumoniae seropositivity (p< 0.05). It was
      concluded that in areas with high C.pneumoniae infection prevalence, early
      diagnosis and specific treatment of C.pneumoniae infections, may prevent
      establishment of chronic infection and eliminate a risk factor for the
      development of atherosclerosis.

PMID- 22399187
TI  - Association of CD27 and CD70 gene polymorphisms with risk of sporadic breast
      cancer in Chinese women in Heilongjiang Province.
AB  - CD27 and its ligand, CD70, are major costimulatory molecules whose interaction
      can regulate the expansion and differentiation of effector and memory T-cell
      populations. Their abnormal expression can disturb the immune response and lead
      to an increased risk of cancer. This study aims to evaluate the associations
      between single nucleotide polymorphisms (SNPs) in CD27/CD70 gene and breast
      cancer susceptibility. Five tagSNPs and one coding polymorphism in CD27, as well
      as three tagSNPs in CD70, were genotyped in a case-control study of 610 breast
      cancer patients and 617 healthy controls. In CD27, rs3136550 CT and rs2267966 AT
      genotypes were associated with a decreased risk of breast cancer (P = 0.03, OR =
      0.76; P = 0.02, OR = 0.75, respectively). In CD70, AG and GG genotypes in
      rs1862511 and CC genotype in rs2059154 also showed significant associations with
      a decreased risk of breast cancer (P = 2.00 * 10(-3), OR = 0.69; P = 0.03, OR =
      0.62; P = 2.00 * 10(-3), OR = 0.53; respectively). Significant associations were
      also found in the dominant and recessive models for rs2059154 and dominant model
      for rs1862511. In haplotype analysis, CCGAG haplotype in CD27 and TAA haplotype
      in CD70 conferred an increased risk of breast cancer (P = 5.60 * 10(-3); P = 7.75
      * 10(-5), respectively), but TGC, TAC and TGA haplotypes in CD70 were associated
      with a decreased risk of breast cancer (P = 0.01; P = 5.2 * 10(-3); P = 2.00 *
      10(-3), respectively). The associations of CCGAG, TAA, TAC and TGA haplotypes
      remained significant after correcting P value for multiple testing. Significant
      associations were shown between the SNPs of CD27 and lymph node metastasis, and
      ER and PR statuses. These results indicate that CD27 and CD70 gene polymorphisms
      may affect the risk of breast cancer and show that some SNPs are associated with
      breast cancer characteristics in a northern Chinese population.

PMID- 22399188
TI  - Invasive lobular breast cancer: subtypes and outcome.
AB  - Invasive lobular carcinoma (ILC) is the most common "special type" of breast
      cancer. Although conflicting literature data are available on the outcome of ILC,
      recently reported data indicate that ILC carries a poorer prognosis if compared
      to invasive ductal carcinomas. We evaluated clinical and biological features of
      981 consecutive patients with pT1-3, pN1-3 M0 ILC. Median follow-up was 7.4 years
      for survival. A total of 541 patients were classified as classic (55.8%), 146
      alveolar (14.9%), 145 mixed non-classic (14.8%), 104 solid (10.6%), and 38
      trabecular (3.9%). A statistically significant difference in the outcome was
      observed at multivariate analysis for patients with solid (HR 2.44, 95% CI 1.39
      4.29 for OS; HR 1.92, 95% CI 1.29-2.88 for DFS) and mixed non-classic (HR 1.99,
      95% CI 1.12-3.53 for OS) versus patients with classical ILC. A statistically
      significant difference in the risk of distant metastases was observed at
      multivariate analysis for patients with Luminal B (HR 2.56, 95% CI 1.38-4.76),
      HER2 positive (HR 7.80, 95% CI 1.55-39.3), and triple negative (HR 7.61, 95% CI
      2.63-22.1) subtypes versus patients with Luminal A ILC. Age >=70 years, tumor
      size and degree of nodal involvement were additional independent predictors of
      reduced overall survival. The outcome of ILC significantly correlated with
      histological and immunohistochemically defined molecular subtypes. New tailored
      strategies should be explored in these subgroups of patients with poor outcome.

PMID- 22399189
TI  - Disparities in breast cancer care delivery: solving a complex puzzle.

PMID- 22399190
TI  - Recurrent germline mutations in BRCA1 and BRCA2 genes in high risk families in
      Israel.
AB  - The spectrum of germline mutations among Jewish non Ashkenazi high risk
      breast/ovarian cancer families includes a few predominant mutations in BRCA1
      (185delAG and Tyr978X) and BRCA2 (8765delAG). A few additional recurring
      mutations [A1708E, 981delAT, C61G (BRCA1) R2336P, and IVS2 + 1G > A (BRCA2)] have
      been reported in Jewish non Ashkenazi families. The 4153delA*BRCA1 C61G*BRCA1 and
      the 4075delGT*BRCA2 has been reported to recur in Russian/Polish non Jews and
      Ashkenazim, respectively. The rate of these recurring mutations has not been
      reported in Israeli high risk families. Genotyping for these recurring mutations
      by restriction enzyme digest and sequencing method was applied to high risk,
      predominantly cancer affected, unrelated Israeli individuals of Ashkenazi (n =
      827), non Ashkenazi (n = 2,777), non Jewish Caucasians (n = 193), and 395 of
      mixed ethnicity. Jewish participants included 827 Ashkenazi, 804 Balkans, 847
      North Africans, 234 Yemenites, and 892 Asians (Iraq and Iran). Age at diagnosis
      of breast cancer (median +/- SD) (n = 2,484) was 47.2 +/- 9.6 for all women
      participants. Males (n = 236) were also included, of whom 24 had breast cancer
      and 35 had pancreatic cancer. Overall, 8/282 (2.8%) of the Balkan cases carried
      the BRCA1*A1708E mutation, 4/180 (2.2%) the R2336P mutation, and 0/270 the IVS2 +
      1G > A BRCA2 mutations, respectively. Of North Africans, 7/264 (2.65%) carried
      the BRCA1*981delAT mutation. The BRCA1*C61G mutation was detected in 3/269
      Ashkenazi, non Ashkenazi, and non Jewish Russians; the BRCA1*Tyr978X mutation was
      detected in 23/3220 individuals of non Ashkenazi origin, exclusively of Asian
      ethnicity (23/892, 2.6% of the Asians tested). The BRCA1*4153delA mutation was
      noted in 2/285 non Jewish Caucasians, and none of the Ashkenazim (n = 500)
      carried the BRCA2*4075delGT mutation. Jewish high risk families of North African,
      Asian, and Balkan descent should be screened for the 981delAT, Tyr978X, A1708E
      BRCA1, and the R2336P BRCA2 mutations, respectively.

PMID- 22399191
TI  - Molecular pathogenesis of IDH mutations in gliomas.
AB  - The isocitrate dehydrogenase 1 (IDH1) or 2 (IDH2) genes are mutated in 50-80% of
      astrocytomas, oligodendrogliomas or oligoastrocytomas of grades II and III, and
      secondary glioblastomas; they are, however, seldom mutated in primary
      glioblastomas and never in other types of glioma. Gliomas with IDH1/2 mutations
      always harbor either TP53 mutations or total 1p/19q loss. This suggests these two
      types of tumor may arise from common progenitor cells that have IDH1/2 mutations,
      subsequently evolving into each tumor type with the acquisition of TP53 mutations
      or total 1p/19q loss. Survival is significantly longer for patients with IDH
      mutated gliomas than for those with IDH-wild type tumors. This observation
      indicates that IDH status defines biologically different subgroups among gliomas.
      The molecular pathogenesis of IDH1/2 mutations in the development of gliomas is
      unclear. The mutated IDH1/2 enzyme generates D-2-hydroxyglutarate. Several
      theories have been proposed, including: increased angiogenesis because of
      accumulation of HIF-1alpha; a glioma CpG island methylator phenotype (G-CIMP)
      induced by inhibition of TET2; and increased vulnerability to oxidative stress
      because of depletion of antioxidants. Elucidating the pathogenesis of IDH
      mutations will aid better understanding of the molecular mechanisms of
      gliomagenesis and may lead to the development of novel molecular classification
      and therapy.

PMID- 22399192
TI  - Downregulation of N-Myc downstream-regulated gene 4 influences patient survival
      in gliomas.
AB  - N-Myc downstream-regulated gene 4 (NDRG4) plays important roles in cellular
      differentiation and neurite formation. It is required for cell cycle progression
      and survival in established glioblastoma cell lines and cancer stem cell-enriched
      cells. The aim of this study was to evaluate the correlation of NDRG4 expression
      with the clinicopathological features and prognosis in patients with gliomas.
      Immunohistochemistry and Western blot analysis were used to investigate the
      expression of NDRG4 protein, respectively, in 128 patients with gliomas.
      Immunohistochemistry showed that NDRG4 expression was significantly reduced in
      glioma relative to nonneoplastic brain tissues (P = 0.008), and that its
      expression decreased with increasing glioma grade. These results were in line
      with the results of Western blot analysis. In addition, a non-parametric analysis
      revealed that the reduced NDRG4 expression was significantly correlated with a
      low Karnofsky performance score (P = 0.01), frequent intra-tumor necrosis (P =
      0.03), and poor overall survival (P = 0.01). Furthermore, multivariate analysis
      showed that NDRG4 expression (P = 0.03) and intra-tumor necrosis (P = 0.03) were
      two important independent prognostic factors identified by the Cox proportional
      hazard model. Our results provide convincing evidence for the first time that the
      expression of NDRG4 is downregulated in human gliomas. The glioma patients with
      lower NDRG4 expression have a poor prognosis.

PMID- 22399193
TI  - Measurement and cellular sources of the soluble interleukin-2 receptor in primary
      central nervous system lymphoma.
AB  - The aims of this study were to determine the diagnostic utility of the serum
      levels of the soluble interleukin 2 receptor (sIL-2R) as a tumor marker of
      primary central nervous system lymphoma (PCNSL) and to investigate the cellular
      source of sIL-2R using immunohistochemical staining. The serum sIL-2R levels of
      37 samples from suspected PCNSL patients were measured. There were 13 patients
      with PCNSL and 24 patients with other diseases such as glioma, metastatic tumor,
      inflammation, or cerebrovascular disease. The serum sIL-2R levels of the PCNSL
      cases and other brain diseases were 629.5 +/- 586.0 U/ml (mean +/- SD; range 189
      2220 U/ml) and 408.5 +/- 250.7 U/ml (160-837 U/ml), respectively. The serum sIL
      2R levels of the two groups overlapped, and hence the difference between them was
      not significant. sIL-2R is the alpha subunit of IL-2R. It is also known as CD25,
      and is cleaved from its position in the cell membrane and released into the
      blood. CD25 expression was immunohistochemically detected in 7 of 11 PCNSL
      samples. Confocal laser microscopy revealed that CD25 signals were present in
      atypical cells and mononuclear cells. We concluded that both lymphoma cells and
      infiltrating T cells express CD25, which is one of the cellular sources of sIL
      2R.

PMID- 22399194
TI  - [Gastric ulcer suspected of being a carcinoma].
AB  - Following hepatic penetration by a gastric ulcer a pitfall diagnosis of gastric
      adenocarcinoma can result from a biopsy of the ulcer base. In cases of suspicious
      "hepatoid" epithelial cells in a gastric biopsy, the possibility of regular liver
      tissue from a gastric ulcer penetrating the liver should be kept in mind and
      verified, e.g. by immunohistochemistry.

PMID- 22399195
TI  - [Tumor of the peroneal compartment].
AB  - Degenerative nuclear atypia in mesenchymal neoplasia, especially in benign nerve
      sheath tumors, may become a pitfall leading to a wrong diagnosis of a sarcoma.
      Using a case of degenerative (ancient) schwannoma as an example, the
      characteristic findings of degenerative atypia are presented and discussed.

PMID- 22399196
TI  - [Prostate biopsy - an unending story].

PMID- 22399199
TI  - Malignant Rectal Gastrointestinal Stromal Tumour: Case Report and Review of
      Literature.

PMID- 22399201
TI  - Superior vena cava obstruction due to pacemaker leads.

PMID- 22399200
TI  - Determination of surface concentrations of individual molecule-layers used in
      nanoscale biosensors by in situ ATR-FTIR spectroscopy.
AB  - For the development of nanowire sensors for chemical and medical detection
      purposes, the optimal functionalization of the surface is a mandatory component.
      Quantitative ATR-FTIR spectroscopy was used in situ to investigate the step-by
      step layer formation of typical functionalization protocols and to determine the
      respective molecule surface concentrations. BSA, anti-TNF-alpha and anti-PSA
      antibodies were bound via 3-(trimethoxy)butylsilyl aldehyde linkers to silicon
      oxide surfaces in order to investigate surface functionalization of nanowires.
      Maximum determined surface concentrations were 7.17 * 10(-13) mol cm(-2) for BSA,
      1.7 * 10(-13) mol cm(-2) for anti-TNF-alpha antibody, 6.1 * 10(-13) mol cm(-2)
      for anti-PSA antibody, 3.88 * 10(-13) mol cm(-2) for TNF-alpha and 7.0 * 10(-13)
      mol cm(-2) for PSA. Furthermore we performed antibody-antigen binding experiments
      and determined the specific binding ratios. The maximum possible ratio of 2 was
      obtained at bulk concentrations of the antigen in the MUg ml(-1) range for TNF
      alpha and PSA.

PMID- 22399202
TI  - Microbiology of cardiac implantable electronic device infections.
AB  - AIMS: The aim of the study was to describe the microbiological findings of
      cardiac implantable electronic devices (CIEDs) infection in the 2000-2011 period
      at the Cardiology Unit of New Santa Chiara Hospital in Pisa (Italy). METHODS AND
      RESULTS: Removed CIED leads and pocket material were seeded on solid media and
      isolates tested for antimicrobial susceptibility with the Kirby Bauer method.
      Electrodes from 1204 patients were analysed and 854 (70.9%) tested positive. In
      663 (77.6%) cases only one species was isolated, in 175 (20.5%) two species, and
      in 14 (1.8%) >2 species. In 116 cases material from the pocket was also cultured.
      The result was consistent with that from the electrodes in 69 (59%) cases. In 359
      cases a blood sample was also obtained for culture. The result was consistent
      with that from the leads in 124 (35%) cases. A total of 1068 strains were
      isolated from electrodes. Gram-positive organisms were most frequently isolated
      (92.5% of isolates); particularly, coagulase-negative staphylococci (CoNS),
      mainly Staphylococcus epidermidis, in 69% of cases and Staphylococcus aureus in
      13.8%, Gram-negative rods in 6.1%, yeasts in 1% and molds in 0.4%. Overall,
      Oxacillin resistance was 30%, in particular 33% among CoNS and 13% among S.
      aureus. Oxacillin resistance and quinolones resistance have increased in the
      period 2006-2011 with respect to the 5 years before. Seventeen percent of
      Enterobacteriaceae strains had a phenotype compatible with extended spectrum beta
      lactamase expression. CONCLUSIONS: Culture of the leads offers the possibility of
      an aetiological diagnosis in the majority of cases. When material from the pocket
      can be obtained, the microbiological result is often consistent with that from
      the electrodes, while species isolated from blood cultures are often different
      and more likely to be the result of contamination. Cardiac implantable electronic
      device infection is more often monomicrobial, CoNS are most frequently isolated
      and S. epidermidis is largely the main single agent. Very early infections were
      associated with S. aureus infection. The pattern of susceptibility to
      antimicrobials is in general that of community-acquired infections, although
      oxacillin resistance and quinolones resistance has increased in the last 5 years.

PMID- 22399203
TI  - Pulmonary vein tachycardia during atrial tachycardia in the context of atrial
      fibrillation ablation.

PMID- 22399204
TI  - Women have better long-term prognosis than men after cardiac resynchronization
      therapy.
AB  - AIMS: Cardiac resynchronization therapy (CRT) improves prognosis in patients with
      moderate-to-severe heart failure, reduced left ventricular ejection fraction, and
      wide QRS complexes. However, CRT may be under-utilized in women and data on long
      term follow-up are still scarce. The aim was to investigate long-term mortality
      and hospitalization and prognostic impact of gender after CRT. METHODS AND
      RESULTS: Data on 619 consecutive patients (19% women) that received CRT at a
      single centre between 1998 and 2008 were collected from electronic medical
      records and national death and hospitalization registries up to 2010. The primary
      endpoint was death of any cause and the secondary endpoint was combined death of
      any cause or heart failure hospitalization. Over a mean follow-up of 1320 +/- 786
      days, 215 (35%) patients reached the primary endpoint and 437 (71%) the secondary
      endpoint. Overall, 1-, 5-, and 10-year survivals were 91, 63, and 39%,
      respectively. Female gender was the only independent predictor of all-cause
      mortality; hazard ratio (HR) 0.44 [95% confidence interval (CI), 0.21-0.90; P=
      0.025]. Women also had a trend towards lower risk for the secondary endpoint, HR
      0.68 (95% CI, 0.45-1.04; P= 0.072). CONCLUSION: In this registry analysis,
      patients with CRT had similarly high short-term survival to those in controlled
      trials, and this favourable prognosis was sustained over the long term.Women had
      lower all-cause mortality than men.

PMID- 22399206
TI  - Quantitative computed tomography (QCT) as a radiology reporting tool by using
      optical character recognition (OCR) and macro program.
AB  - The objectives are (1) to introduce a new concept of making a quantitative
      computed tomography (QCT) reporting system by using optical character recognition
      (OCR) and macro program and (2) to illustrate the practical usages of the QCT
      reporting system in radiology reading environment. This reporting system was
      created as a development tool by using an open-source OCR software and an open
      source macro program. The main module was designed for OCR to report QCT images
      in radiology reading process. The principal processes are as follows: (1) to save
      a QCT report as a graphic file, (2) to recognize the characters from an image as
      a text, (3) to extract the T scores from the text, (4) to perform error
      correction, (5) to reformat the values into QCT radiology reporting template, and
      (6) to paste the reports into the electronic medical record (EMR) or picture
      archiving and communicating system (PACS). The accuracy test of OCR was performed
      on randomly selected QCTs. QCT as a radiology reporting tool successfully acted
      as OCR of QCT. The diagnosis of normal, osteopenia, or osteoporosis is also
      determined. Error correction of OCR is done with AutoHotkey-coded module. The
      results of T scores of femoral neck and lumbar vertebrae had an accuracy of 100
      and 95.4 %, respectively. A convenient QCT reporting system could be established
      by utilizing open-source OCR software and open-source macro program. This method
      can be easily adapted for other QCT applications and PACS/EMR.

PMID- 22399205
TI  - Androgenesis-inducing stress treatments change phytohormone levels in anthers of
      three legume species (Fabaceae).
AB  - Legumes are recalcitrant to androgenesis and induction protocols were only
      recently developed for pea (Pisum sativum L.) and chickpea (Cicer arietinum L.),
      albeit with low regeneration frequencies. Androgenesis is thought to be mediated
      through abscisic acid (ABA) but other phytohormones, such as auxins, cytokinins,
      and gibberellins, have also been implicated. In view of improving induction
      protocols, the hormone content of pea, chickpea, and lentil anthers was measured
      after exposure to cold, centrifugation, electroporation, sonication, osmotic
      shock, or various combinations thereof using an analytical mass spectrometer.
      Indole-3-acetic acid (IAA) had a key function during the induction process. In
      pea, high concentrations of IAA-asparagine (IAA-Asp), a putative IAA metabolite,
      accumulated during the application of the different stresses. In chickpea, the
      IAA-Asp concentration increased 30-fold compared to pea but only during the
      osmotic shock treatment and likely as a result of the presence of exogenous IAA
      in the medium. In contrast, no treatment in lentil (Lens culinaris) invoked such
      an increase in IAA-Asp content. Of the various cytokinins monitored, only cis
      zeatin riboside increased after centrifugation and electroporation in pea and
      possibly chickpea. No bioactive gibberellins were detected in any species
      investigated, indicating that this hormone group is likely not linked to
      androgenesis in legumes. In contrast to the other stresses, osmotic shock
      treatment caused a reduction in the levels of all hormones analyzed, with the
      exception of IAA-Asp in chickpea. A short period of low hormone content might be
      a necessary transition phase for androgenesis induction of legumes. KEY MESSAGE:
      Five androgenesis-inducing stress treatments changed content of ABA, auxin and
      cytokinin in anthers of three legumes. Osmotic shock treatment differed because
      it reduced hormone content to very low levels.

PMID- 22399207
TI  - Effects of sildenafil in Nomega-nitro-L-arginine methyl ester-induced
      intrauterine growth restriction in a rat model.
AB  - OBJECTIVE: To assess the effect of sildenafil citrate in a rat model of Nomega
      nitro-l-arginine methyl ester (L-NAME)-induced intrauterine growth restriction
      (IUGR). STUDY DESIGN: An in vivo experimental study was conducted where 40
      pregnant Sprague-Dawley rats were randomly assigned to receive either: (1)
      control, (2) L-NAME 50 mg/kg/d by gavage (days 14 to 19), (3) L-NAME and
      sildenafil 15 mg/kg/d by gavage, or (4) sildenafil (days 14 to 21). On day 21, a
      hysterotomy was performed and all fetuses (live and dead) were counted, examined,
      and weighed. The primary outcome measure was the difference in pup birth weight.
      RESULTS: The median number of live pups per dam was 11.5 (range: 1 to 15), 13.5
      (2 to 17), 13.5 (7 to 16), and 11.5 (4 to 17) in controls, L-NAME, sildenafil,
      and combined drug groups, respectively (p = 0.02). Rats treated with L-NAME had a
      significantly higher number of stillbirths compared with control (p = 0.013) and
      sildenafil (p = 0.008) groups. L-NAME reduced pup birth weight compared with
      controls (4.53 +/- 1.49 versus 5.65 +/- 1.63 g, p < 0.001); this effect was more
      pronounced in the L-NAME and sildenafil groups (3.37 +/- 1.25 g, p < 0.001).
      CONCLUSION: Our data indicate that sildenafil citrate does not ameliorate L-NAME
      induced IUGR, and in the doses utilized in this study might even have a
      synergistic negative effect on pup birth weight.

PMID- 22399208
TI  - Yoga during pregnancy: a review.
AB  - The purpose of this review article is to evaluate the peripartum outcomes of yoga
      during pregnancy, including the postpartum period and lactation. The PubMed
      database was analyzed from January 1970 to January 2011. We identified five
      prospective observational studies (n = 575) and three randomized clinical trials
      (RCTs; n = 298), which were analyzed separately. The nonrandomized trials
      indicated a significant reduction in rates of preterm labor (p < 0.0006),
      intrauterine growth retardation (p <0.003), low birth weight (p < 0.01),
      pregnancy discomforts (p = 0.01), and perceived sleep disturbances (p = 0.03) in
      those who practiced yoga during pregnancy. Results of the RCTs indicated that
      doing yoga during pregnancy can significantly lower pain and discomfort (p <
      0.05) and perceived stress (p = 0.001) and improve quality of life in physical
      domains (p = 0.001). All three RCTs were poorly compliant with the Consolidated
      Standard of Reporting Trials statement. While awaiting an appropriately designed
      RCT to determine the benefits of yoga during pregnancy, it remains a viable
      exercise option.

PMID- 22399209
TI  - Intrapartum fetal heart rate characteristics of nonanomalous fetuses with trisomy
      21.
AB  - OBJECTIVE: To compare the intrapartum fetal heart rate (FHR) characteristics and
      selected birth outcomes of nonanomalous trisomy 21 (T21) fetuses to matched
      controls. STUDY DESIGN: Nonanomalous, non-growth-restricted T21 infants were
      identified and matched by gestational age to presumed euploid controls. We
      excluded women with scheduled cesarean deliveries and multiple gestations. The
      incidence of abnormal FHR patterns within 3 hours of delivery and birth outcomes
      were compared between T21 fetuses and controls. The presence of any abnormal FHR
      pattern was the primary outcome. Birth outcomes included 5-minute Apgar <7,
      neonatal intensive care unit admission, and cesarean delivery for fetal
      indications. RESULTS: Forty-four T21 infants and 44 controls were compared. Of
      the T21 infants, 83% were postnatally diagnosed. No significant differences were
      noted in the primary outcome (68% versus 59%, p = 0.37) or birth outcomes.
      CONCLUSION: T21 is not associated with an increased incidence of abnormal FHR
      patterns or adverse birth outcomes compared with presumed euploid fetuses.

PMID- 22399210
TI  - Prediction of survival in infants with congenital diaphragmatic hernia based on
      stomach position, surgical timing, and oxygenation index.
AB  - OBJECTIVE: To identify characteristics predictive of survival of patients with
      congenital diaphragmatic hernia (CDH). STUDY DESIGN: Retrospective analysis of
      clinical characteristics including severity of lung disease measured by
      oxygenation index (OI) associated with single-center survival in CDH patients (n
      = 81) from 1992 to 2008. Data were analyzed using univariate and multivariable
      logistic regression, effect plots, and receiver operating characteristic (ROC)
      plots. RESULTS: No patient died if the stomach was located in the abdomen. A left
      thoracic stomach position predicted decreased survival with ROC area under the
      curve (AUC) = 0.70. OI of <= 26 averaged over the first 12 hours of life
      predicted >= 50% survival for all patients, with AUC = 0.86. OI effect plots
      allow prediction of survival over a continuous OI range. No patient survived if
      mean OI was >51 in the first 12 hours of life. Delaying surgery for a median of 6
      days improved survival probability for all patients with presurgery OI values <=
      51. CONCLUSION: Position of the stomach in the abdomen, delayed surgery, and less
      severe cardiopulmonary disease during the first 12 hours of life, as measured by
      mean OI, predicted improved survival probability among patients with CDH. Our CDH
      model, using mean OI, permits specific individual prediction of survival
      probability over a range of OI values.

PMID- 22399211
TI  - Association of abdominal aortic wall thickness in the newborn with maternal
      factors.
AB  - PURPOSE: The goal of the present study is to carry out prospective
      echocardiographic measurements of intima-media thickness (IMT) in the abdominal
      artery of newborns. METHODS: Study subjects were 96 mothers and their newborns.
      We measured the adjusted IMT (aIMT, mm/mm) of newborn abdominal arteries by high
      resolution ultrasound and evaluated the association of aIMT with various maternal
      and newborn factors. RESULTS: Negative correlations were observed between aIMT
      and gestational age (r = - 0.678, p < 0.01) and positive correlations between
      aIMT and placenta-to-fetus weight ratio (r = 0.418, p < 0.01). Comparing the
      small-for-gestational-age (SGA) versus appropriate-for-gestational-age (AGA)
      categories, aIMT in the SGA (n = 14) was greater than in the AGA (n = 82), with
      values of [0.115 (0.117) mm/mm versus 0.084 (0.074) mm/mm, p < 0.01],
      respectively. A multiple linear regression analysis was performed with aIMT as a
      dependent variable, and significant correlations were noted with gestational age
      (R2 = 0.524, beta = - 0.515, p < 0.001 for gestational age). CONCLUSION: On the
      basis of these findings, we suggest that aIMT thickness is associated with
      placenta-to-fetus weight ratio and gestational age, and that increased values of
      aIMT in SGA may indicate presence of a latent link to cardiovascular disease that
      might otherwise go undetected in infancy.

PMID- 22399212
TI  - Hemolytic disease of the newborn caused by irregular blood subgroup (Kell, C, c,
      E, and e) incompatibilities: report of 106 cases at a tertiary-care centre.
AB  - OBJECTIVE: To determine the clinical spectrum of hemolytic disease due to
      irregular blood subgroup incompatibility in hospitalized neonates. STUDY DESIGN:
      The medical records of the all hospitalized newborn patients diagnosed with
      indirect hyperbilirubinemia due to subgroup incompatibility in Kell, C, c, E, and
      e systems were included in the study. Data from 106 newborns with hemolytic
      jaundice due to irregular blood subgroups were retrospectively evaluated, and
      clinical and laboratory findings were compared between patients . The treatment
      modalities given to the patients of each subgroup types and the laboratory
      findings and treatment modalities of the cases according to Coombs tests results
      were also analyzed. Fetal affection of the hemolysis and also fetal losses due to
      irregular red-cell alloimmunization were not detected in prenatal course, as
      there was no follow-up of these pregnancies. RESULTS: The mean postnatal
      hospitalizing age was 6.1 +/- 5.2 days after birth. The mean total bilirubin
      level and the mean hemoglobin value on hospitalization were 343.7 +/- 63.3 umol/L
      (=20.1 +/- 3.7 mg/dL) and 14.9 +/- 3.4 g/dL, respectively. Of 106 patients
      identified with irregular subgroup incompatibility, 40 infants (37.7%) were
      associated with C, 22 (20.8%) with c, 30 (28.3%) with E, 9 (8.5%) with e, and 5
      (4.7%) with Kell subgroup system. Positive Coombs tests (either direct and/or
      indirect) occurred in 28.3% of the study cases. Hydrops fetalis was determined in
      5 of 106 neonates (4.7%). Twenty-two of 106 (20.8%) patients required total
      exchange transfusion. Positive Coombs test in cases required total exchange
      transfusion was 63.6%. CONCLUSION: Our data expose the magnitude and spectrum of
      the potential developing severe hemolytic disease and immune hydrops due to
      irregular subgroup incompatibility. Minor group antibody screening is recommended
      both in the mother and the high-risk infants with hyperbilirubinemia and
      hemolytic disease of the newborn.

PMID- 22399213
TI  - Pregnancy outcomes of managed Medicaid members prescribed home administration of
      17 alpha-hydroxyprogesterone caproate.
AB  - OBJECTIVE: Examine adherence to treatment guidelines and rates of recurrent
      spontaneous preterm birth (SPTB) in managed Medicaid patients prescribed 17 alpha
      hydroxyprogesterone caproate (17P). STUDY DESIGN: A retrospective observational
      study of women receiving 17P between July 2004 and May 2010 through one of
      Centene's managed Medicaid programs. Included for analysis were singleton
      pregnancies without cerclage having SPTB history and prescribed 17P by their
      physician. Compounded 17P was administered through an outpatient program
      inclusive of patient education, weekly home nurse visits, and 24-7 telephonic
      nurse access. A health plan-directed pregnancy management program, Start Smart
      for Your Baby((r)), supported the therapy with case management activities.
      RESULTS: Of the 790 patients studied, 58.6% initiated 17P in the recommended 16-
      to 20.9-week gestational age window. Elective discontinuation of 17P occurred in
      18.6%. Of the 10,583 17P injections administered, 97.5% were administered within
      the recommended injection interval of 6 to 10 days. Recurrent SPTB occurred in
      28.2% of women studied. CONCLUSION: Managed Medicaid patients enrolled in an
      outpatient 17P administration program supported with maternal case management
      have high rates of treatment compliance. Their pregnancy outcomes compare
      favorably to previously published reports that include both Medicaid and
      commercially insured patients.

PMID- 22399214
TI  - Prenatal methamphetamine exposure and short-term maternal and infant medical
      outcomes.
AB  - OBJECTIVE: Examine maternal and infant medical outcomes of prenatal exposure to
      methamphetamine (MA). STUDY DESIGN: Four hundred and twelve mother-infant pairs
      (204 MA-exposed and 208 unexposed matched comparisons) were enrolled in the
      Infant Development, Environment and Lifestyle (IDEAL) study. Exposure was
      determined by maternal self-report during this pregnancy and/or positive meconium
      toxicology. Maternal interviews assessed prenatal drug use, pregnancy course, and
      sociodemographic information. Medical chart reviews provided medical history,
      obstetric complications, infant outcomes, and discharge placement. RESULTS: MA
      using mothers were more likely to be poor, to have a psychiatric
      disorder/emotional illness and less prenatal care, and to be less likely to
      breast-feed their infant than comparison mothers. After adjusting for covariates,
      MA-exposed infants were more likely to exhibit poor suck, to have smaller head
      circumferences and length, to require neonatal intensive care unit (NICU)
      admission, and to be referred to child protective services (CPS). Several
      outcomes previously reported from studies that lacked adequate control groups or
      adjustment for covariates were not significantly different in this study.
      CONCLUSION: Prenatal MA exposure is associated with maternal psychiatric
      disorder/emotional illness, poor suck, NICU admission, and CPS involvement, and
      MA-exposed infants were less likely to be breast-fed; however, the absence of
      many serious complications, such as fetal distress, chronic hypertension,
      preeclampsia, placenta previa, abruptio placentae, and cardiac defects, suggests
      confounding variables influenced prior studies.

PMID- 22399215
TI  - Perinatal arterial ischemic stroke in northern Queensland.
AB  - OBJECTIVES: Our objective was to review the occurrence, presentation, and
      associated risk factors of stroke in infants at a tertiary neonatal intensive
      care unit. STUDY DESIGN: Inpatient electronic records identified infants between
      March 2002 and March 2011 who had perinatal arterial ischemic stroke. RESULTS:
      Ten infants had perinatal arterial ischemic stroke, 50% were outborn, 20% were
      indigenous, and mortality was 30%. Median birth weight was 2970 g (range 1699 to
      3443 g), and median gestation was 36 weeks (range 32 to 41 weeks). Perinatal
      arterial ischemic stroke were left sided in three, right sided in three, and
      bilateral in four. Presentation included four with seizures, four with
      apnea/sepsis, one with thrombosis, and one without symptoms. In 4 of 10 cases
      reported in this series, there was a maternal history of gestational diabetes,
      although the incidence of gestational diabetes in Australia is only 4.5%.
      CONCLUSION: The incidence of gestational diabetes mellitus in our cases appears
      to be very much higher than the average population. Larger studies are needed to
      determine if gestational diabetes mellitus is a risk factor for perinatal
      arterial ischemic stroke.

PMID- 22399216
TI  - Proteomic analysis of lamellar bodies isolated from amniotic fluid: implications
      for function.
AB  - Lamellar body count (LBC) in amniotic fluid is a well-established method for
      assessing fetal lung maturity. However, the biogenesis and function of lamellar
      bodies (LBs) secreted into the amniotic fluid have not been formally assessed. We
      purified LBs from amniotic fluids obtained from term gestation pregnancies that
      had been determined to have mature LBC. Using tandem mass spectrometry, we
      identified 122 unique proteins in the LB preparations from the amniotic fluids.
      There was minimal overlap between the proteins identified in amniotic fluid LB
      and those reported for human epidermis LB. In contrast, there was >40%
      concordance with the proteome of rat lung LBs despite species differences.
      Classification of the identified proteins into functional bins demonstrated that
      the preponderance of amniotic fluid LB proteins was associated with host defense
      or anti-inflammatory functions. These data suggest that amniotic fluid LBs are
      derived from lung secretions and may play an important role in innate host
      defense of the fetus.

PMID- 22399217
TI  - Comparison of bactericidal properties of alcohol-based chlorhexidine versus
      povidone-iodine prior to amniocentesis.
AB  - OBJECTIVE: To compare the bactericidal properties of povidone-iodine versus
      alcohol-based chlorhexidine solution for cleansing the gravid abdomen prior to
      amniocentesis. METHODS: Fifty study participants were recruited from the
      University of Texas Women's Clinic in Houston, Texas. Two baseline swabs of the
      patients' abdomens were obtained to assess bacterial flora prior to treatment. A
      10% povidone-iodine solution and 2% chlorhexidine gluconate with 70% isopropyl
      alcohol solution in a 3-mL prefilled applicator (Chloraprep, Cardinal Health,
      Inc., Leawood, KS) were then applied on different sides of the abdomen. After 30
      seconds, cultures were obtained and plated on Trypticase Soy (PML
      Microbiologicals, Durham, NC) with sheep's blood agar for aerobic flora. Plates
      were incubated at 37 degrees C for 48 hours for aerobic flora. Colony-forming
      units were counted and recorded. RESULTS: No statistically significant difference
      was detected between baseline colony counts between the left and right side of
      each patient's abdomen (p = 0.33) prior to cleansing. Postcleansing colony counts
      were evaluated, and a statistically significant difference was identified,
      favoring chlorhexidine as a more efficacious abdominal cleanser (p <0.001).
      CONCLUSION: We demonstrated that 2% chlorhexidine with 70% isopropyl alcohol had
      excellent bactericidal efficacy and was superior to povidone-iodine for cleansing
      the maternal abdomen.

PMID- 22399218
TI  - Neural tube defects and associated low birth weight.
AB  - OBJECTIVE: To estimate the association between neural tube defects (NTDs) and low
      birth weight. STUDY DESIGN: This was a retrospective cohort study of women
      undergoing ultrasound from 17 to 22 weeks from 1990 to 2008. Presence or absence
      of fetal NTD defined the two study groups. The primary outcomes were intrauterine
      growth restriction (IUGR), birth weight <10th percentile, and severe IUGR <5th
      percentile. Subgroup analysis was performed to observe if the association with
      IUGR persisted. RESULTS: Of 66,956 women, 170 were found to have fetal NTD. Only
      the rate of advanced maternal age differed between the study groups. Fetuses with
      an NTD were at significantly increased risk for IUGR <10th percentile (adjusted
      odds ratio [aOR] 2.6, 95% confidence interval [CI] 1.8 to 3.9) and <5th
      percentile (aOR 2.8, 95% CI 1.9 to 4.3). The association persisted in subgroup
      analyses. CONCLUSION: Fetuses with NTD are at increased risk for IUGR, suggesting
      that a policy of serial growth scans in cases with isolated NTD is justified.

PMID- 22399219
TI  - The association of gestational weight gain per institute of medicine guidelines
      and prepregnancy body mass index on outcomes of twin pregnancies.
AB  - OBJECTIVE: To determine if current recommendations for weight gain in twin
      pregnancies according to maternal prepregnancy body mass index (PPBMI) influence
      perinatal outcomes. METHODS: We identified women with twins enrolled in a
      maternity risk screening and education program with initial screening and
      prenatal care initiated at <20 weeks and delivery at >23.9 weeks. Women with
      normal, overweight, or obese PPBMI were included (n = 5129). Pregnancy outcomes
      were compared between those women with weight gain meeting or exceeding 2009
      Institute of Medicine recommendations and patients who did not meet weight gain
      guidelines. RESULTS: Rates of spontaneous preterm delivery at <35 weeks were
      higher in all PPBMI groups for those with weight gain below guidelines. In all
      PPBMI groups, numbers of pregnancies with both infants weighing >2500 g or >1500
      g were significantly higher for women gaining weight at or above guidelines.
      Logistic regression analysis was utilized to assess multivariate impact on
      outcome of spontaneous preterm delivery at <35 weeks showing that regardless of
      PPBMI level, women who gain below recommended guidelines are 50% more likely to
      deliver spontaneously at <35 weeks. CONCLUSION: In twin pregnancies, weight gain
      below recommended guidelines determined by maternal PPBMI is associated with
      higher rates of spontaneous preterm delivery at <35 weeks.

PMID- 22399220
TI  - Staphylococcus aureus, including community-acquired methicillin-resistant S.
      aureus, in a level III NICU: 2001 to 2008.
AB  - OBJECTIVE: To determine epidemiology and clinical characteristics of infants with
      methicillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA) in a
      level III neonatal intensive care unit (NICU). STUDY DESIGN: All NICU admissions
      (2001 to 2008) with any positive S. aureus culture were included as cases. Cases
      were further characterized as either colonized or infected with invasive disease.
      RESULTS: Four thousand three hundred four infants were admitted; 273 (6.3%) had
      at least one culture positive for S. aureus, including 198 with MSSA and 75 with
      MRSA. Invasive disease occurred in 23.2% of MSSA cases versus 29.3% MRSA (p =
      0.298). Between the study periods 2001 to 2005 versus 2006 to 2008, the incidence
      of all MSSA cultures (colonization and invasive disease) decreased from 53.6 to
      38.9/1000 admissions (p = 0.044), and that of MRSA increased from 13.7 to
      24.77/1000 admissions (p = 0.010). The incidence of invasive MSSA (p = 0.49) and
      MRSA (p = 0.38) disease between the two periods remained similar. Infants with
      invasive MRSA versus MSSA had a longer duration of positive cultures (55 versus
      19 days, p = 0.009). None of five available isolates collected prior to 2006 was
      characterized as USA300, but 11/21 isolates collected subsequently were USA300 (p
      = 0.053). CONCLUSION: The incidence of MRSA (colonization and infection) nearly
      doubled during the study period coinciding with emergence of community-acquired
      MRSA USA300.

PMID- 22399221
TI  - Measurement of fetal heart rate variability on an electronic monitor using a
      prototype electronic ruler.
AB  - OBJECTIVE: To develop a prototype electronic ruler for assessment of fetal heart
      rate (FHR) variability on an electronic monitor and test its reliability and
      accuracy. STUDY DESIGN: A prototype electronic ruler was designed and developed
      for assessment of FHR variability on electronic monitors. The electronic ruler
      consisted of horizontal bands that were sized and colored to embed the four FHR
      variability categories. The reliability and accuracy of using the electronic
      ruler to assess FHR variability was studied with expert clinicians. RESULTS:
      Intrarater and interrater reliability was moderate for both the electronic ruler
      and paper strips. The amplitude measurement accuracy of expert variability
      assessment compared with a gold standard was significantly improved (p < 0.001)
      with the electronic ruler versus paper strips. The accuracy of subjects' FHR
      variability category responses compared with the gold standard revealed no
      significant difference (p = 0.50) using either display type. CONCLUSION:
      Performance of the electronic ruler was equivalent to paper strips, which may aid
      assessment of variability on electronic monitors as paper strips become less
      prevalent.

PMID- 22399222
TI  - Cervical cerclage: one stitch or two?
AB  - OBJECTIVE: We sought to determine whether routine placement of a second stitch at
      the time of cervical cerclage improves its efficacy. STUDY DESIGN: This is a
      retrospective cohort study of patients who had cervical cerclage placement at a
      single institution. Operative reports, ultrasound images, and delivery records
      were reviewed. Pregnancy outcomes of patients receiving a two-stitch cerclage
      were compared with those who received a one-stitch cerclage, with a primary
      outcome of spontaneous preterm delivery at <35 weeks' gestation. Univariable,
      multivariable, and Kaplan-Meier survival analyses were performed. RESULTS: Of 146
      patients, 63 had two stitches and 83 had one. Baseline characteristics and
      indications for cerclage were similar except for differences in history of prior
      cerclage and multiple gestations. The two-stitch approach was associated with a
      greater median cerclage height (20 mm versus 17 mm, p = 0.008), but there was no
      difference in spontaneous preterm delivery at <35 weeks' gestation (47.6% versus
      41.0%, adjusted odds ratio 1.22, p = 0.630). CONCLUSION: A two-stitch approach to
      cervical cerclage increases cerclage height, but may not improve efficacy.

PMID- 22399223
TI  - Systematic review of cesarean scar assessment in the nonpregnant state: imaging
      techniques and uterine scar defect.
AB  - OBJECTIVE: To review the ability of imaging techniques to predict incomplete
      healing of uterine cesarean scars before the next pregnancy. STUDY DESIGN: A
      systematic literature review searched for studies on women who underwent previous
      low-transverse cesarean, evaluated by hysterography, sonohysterography (SHG), or
      transvaginal ultrasound (TVU). The median prevalence of scar defects was computed
      with 95% confidence intervals (95% CIs). Odds ratio (OR, 95% CI) identified risk
      factors of incomplete healing. RESULTS: The analysis included 21 studies. The
      proportions of suspected scar defects detected by hysterography, SGH, and TVU
      were 58% (33 to 70), 59% (58 to 85), and 37% (20 to 65), respectively. Two
      studies found that women with a large uterine scar defect had a higher risk of
      uterine rupture or uterine scar dehiscence than those with no scar defect or
      small scar defect (OR: 26.05 [2.36 to 287.61], p <0.001). The only reported risk
      factor for scar defect was the occurrence of more than one previous cesarean (OR:
      2.24 [1.13, 4.45], p = 0.02). CONCLUSION: Hysterography, SGH, and TVU can detect
      uterine scar defects in ~50% of women with previous cesarean.

PMID- 22399224
TI  - Are judgments of learning made after correct responses during retrieval practice
      sensitive to lag and criterion level effects?
AB  - Although successful retrieval practice is beneficial for memory, various factors
      (e.g., lag and criterion level) moderate this benefit. Accordingly, the efficacy
      of retrieval practice depends on how students use retrieval practice during
      learning, which in turn depends on accurate metacognitive monitoring. The present
      experiments evaluated the extent to which judgments of learning (JOLs) made after
      correct responses are sensitive to factors (i.e., lag and criterion level) that
      moderate retrieval practice effects, as well as which cues influence JOLs under
      these conditions. Participants completed retrieval practice for word pairs with
      either short or long lags between practice trials until items were correctly
      recalled 1, 3, 6, or 9 times. After the criterion trial for an item, participants
      judged the likelihood of recalling that item on the final test 1 week later. JOLs
      showed correct directional sensitivity to criterion level, with both final test
      performance and JOLs increasing as criterion level increased. However, JOLs
      showed incorrect directional sensitivity to lag, with greater performance but
      lower JOLs for longer versus shorter lags. Additionally, results indicated that
      retrieval fluency and metacognitive beliefs about criterion level--but not lag-
      influenced JOLs.

PMID- 22399225
TI  - Hip fracture incidence from 1981 to 2009 in the Czech Republic as a basis of the
      country-specific FRAX model.
AB  - The aim of this study was to calculate rates of hospitalization for hip fracture
      and the incidence of hip fractures in the Czech Republic over a period of 29
      years. A second aim was to use the most recent data to populate a FRAX((r)) model
      for the assessment of fracture probability in individual patients. Data on
      hospitalizations for hip fracture (1981-2009) and number of women and men with
      hip fractures (2000-2009) were obtained, and incidences were computed for the
      entire population >=50 years of age. Incidence of hospitalization for hip
      fracture in the Czech population aged >=50 years increased progressively by
      calendar year. Age-standardized incidence of hip fractures increased to 2004 but
      leveled off thereafter and decreased after 2005. Data for hip fracture risk in
      2008 and 2009 and the death hazard were used to populate a Czech-specific FRAX
      model for the computation of 10-year fracture probability. The customized FRAX
      model, using the verified epidemiological data, will be used to identify patients
      at increased fracture risk.

PMID- 22399226
TI  - Involvement of GnRH, PACAP and PRP in the reproduction of blue gourami females
      (Trichogaster trichopterus).
AB  - In vertebrates, gonadotropin-releasing hormone (GnRH) and pituitary adenylate
      cyclase-activating polypeptide (PACAP) are key hormones regulating growth and
      reproduction in the brain-pituitary axis. The regulating hormonal interactions
      are of great interest, therefore, the aim of this study is to provide novel
      insights into the involvement of brain GnRH and PACAP in oogensis and
      spermatogenesis in a fish model, the blue gourami (Trichogaster trichopterus).
      cDNA cloning of two GnRH forms combined with phylogenetic analysis revealed that
      three paralogous GnRH forms exist in blue gourami and evolve as a result of
      genome duplication. GnRH1 mRNA levels are related to final oocyte maturation
      (FOM), and this peptide stimulated beta follicle-stimulating hormone (betaFSH)
      and growth hormone (GH) gene expression; GnRH2 stimulated beta gonadotropins
      (GtH) gene expression and GnRH analog combined with PACAP-38 synergistically
      upregulate GH and betaFSH gene expression. The data presented, together with
      previous studies in our lab, enable suggesting mechanisms explaining the
      physiological relevance of these peptides in the regulation of gametogenesis and
      steroidogenesis in blue gourami females. These findings support the biological
      importance of the GnRH and PACAP hormones family, enabling them to stimulate
      differential biological functions in the regulation of growth and reproduction.

PMID- 22399227
TI  - Sp1 regulates human huntingtin gene expression.
AB  - Huntington's disease (HD) is a hereditary neurodegenerative disorder resulting
      from the expansion of a polyglutamine tract in the huntingtin protein. The
      expansion of cytosine-adenine-guanine repeats results in neuronal loss in the
      striatum and cortex. Mutant huntingtin (HTT) may cause toxicity via a range of
      different mechanisms. Recent studies indicate that impairment of wild-type HTT
      function may also contribute to HD pathogenesis. However, the mechanisms
      regulating HTT expression have not been well defined. In this study, we cloned
      1,795 bp of the 5' flanking region of the human huntingtin gene (htt) and
      identified a 106-bp fragment containing the transcription start site as the
      minimal region necessary for promoter activity. Sequence analysis reveals several
      putative regulatory elements including Sp1, NF-kappaB, HIF, CREB, NRSF, P53, YY1,
      AP1, and STAT in the huntingtin promoter. We found functional Sp1 response
      elements in the huntingtin promoter region. The expression of Sp1 enhanced
      huntingtin gene transcription and the inhibition of Sp1-mediated transcriptional
      activation reduced huntingtin gene expression. These results suggest that Sp1
      plays an important role in the regulation of the human huntingtin gene expression
      at the mRNA and protein levels. Our study suggests that the dysregulation of Sp1
      mediated huntingtin transcription, combining with mutant huntingtin's detrimental
      effect on other Sp1-mediated downstream gene function, may contribute to the
      pathogenesis of HD.

PMID- 22399229
TI  - Neural fields with fast learning dynamic kernel.
AB  - We introduce a modified-firing-rate model based on Hebbian-type changing synaptic
      connections. The existence and stability of solutions such as rest state, bumps,
      and traveling waves are shown for this type of model. Three types of kernels,
      namely exponential, Mexican hat, and periodic synaptic connections, are
      considered. In the former two cases, the existence of a rest state solution is
      proved and the conditions for their stability are found. Bump solutions are shown
      for two kinds of synaptic kernels, and their stability is investigated by
      constructing a corresponding Evans function that holds for a specific range of
      values of the kernel coefficient strength (KCS). Applying a similar method, we
      consider exponential synaptic connections, where traveling wave solutions are
      shown to exist. Simulation and numerical analysis are presented for all these
      cases to illustrate the resulting solutions and their stability.

PMID- 22399231
TI  - Survival estimation through the cumulative hazard function with monotone natural
      cubic splines.
AB  - In this paper we explore the estimation of survival probabilities via a smoothed
      version of the survival function, in the presence of censoring. We investigate
      the fit of a natural cubic spline on the cumulative hazard function under
      appropriate constraints. Under the proposed technique the problem reduces to a
      restricted least squares one, leading to convex optimization. The approach taken
      in this paper is evaluated and compared via simulations to other known methods
      such as the Kaplan Meier and the logspline estimator. Our approach is easily
      extended to address estimation of survival probabilities in the presence of
      covariates when the proportional hazards model assumption holds. In this case the
      method is compared to a restricted cubic spline approach that involves maximum
      likelihood. The proposed approach can be also adjusted to accommodate left
      censoring.

PMID- 22399228
TI  - beta2-adrenergic receptor and astrocyte glucose metabolism.
AB  - Astrocyte glucose metabolism functions to maintain brain activity in both normal
      and stress conditions. Dysregulation of astrocyte glucose metabolism relates to
      development of neuronal disease, such as multiple sclerosis and Alzheimer's
      disease. In response to acute stress, beta2-adrenergic receptor is activated and
      initiates multiple signaling events mediated by Gs, Gi, arrestin, or other
      effectors depending on specific cellular contexts. In astrocytes, beta2
      adrenergic receptor promotes glucose uptake through GLUT1 and accelerates
      glycogen degradation via coupling to Gs and second messenger cAMP-dependent
      pathway. Beta2-adrenergic receptor may regulate other steps in astrocyte glucose
      metabolism, such as lactate production or transduction. Inappropriate regulation
      of beta2-adrenergic receptor activity can disrupt normal glucose metabolism, and
      leads to accelerate neuronal disease development. It was demonstrated that the
      absence of beta2-adrenergic receptor in astrocytes occurred in multiple sclerosis
      patients, and the increased beta2-adrenergic receptor activity relates to
      Alzheimer's disease. A clear view of beta2-adrenergic receptor-mediated signaling
      pathways in regulating astrocyte glucose metabolism could help us to develop
      neuronal diseases treatment by targeting to the beta2-adrenergic receptor.

PMID- 22399232
TI  - Calcium buffering and clearance in spider mechanosensory neurons.
AB  - Spider VS-3 mechanoreceptor neurons have a low-voltage-activated Ca2+ current
      that raises intracellular calcium concentration [Ca2+] when they are depolarized
      by agonists of GABAA receptors or fire action potentials. The Ca2+ rise produces
      negative feedback by modulating the mechanoreceptor current and regulates Ca2+-
      and voltage-activated K+ currents. However, nothing is known about Ca2+ buffering
      in VS-3 neurons. Dynamic changes in VS-3 neuron intracellular [Ca2+] were
      measured using the fluorescent Ca2+ indicator Oregon Green BAPTA-1 (OG488) to
      understand Ca2+ buffering and clearance. Intracellular OG488 concentration
      increased slowly over more than 2 h as it diffused through a sharp intracellular
      microelectrode and spread through the cell. This slow increase was used to
      measure endogenous Ca2+ buffering and clearance by the added buffer technique,
      with OG488 acting as both added exogenous buffer and Ca2+ indicator. [Ca2+] was
      raised for brief periods by regular action potential firing, produced by pulsed
      electric current injection through the microelectrode. The resulting rise and
      fall of [Ca2+] were well fitted by the single compartment model of Ca2+ dynamics.
      With earlier ratiometric [Ca2+] estimates, these data gave an endogenous Ca2+
      binding ratio of 684. Strong Ca2+ buffering may assist these neurons to deal with
      rapid changes in mechanical inputs.

PMID- 22399233
TI  - Associations of intakes of fat, dietary fiber, soy isoflavones, and alcohol with
      levels of sex hormones and prolactin in premenopausal Japanese women.
AB  - OBJECTIVE: Endogenous sex hormones have been implicated in the etiology of breast
      cancer. Dietary factors such as fat, dietary fiber, soy isoflavones, and alcohol
      have been suggested to influence endogenous estrogen and other steroid hormone
      levels. We examined the relationship among these dietary factors and plasma sex
      hormone levels in premenopausal Japanese women. METHODS: We measured the plasma
      concentrations of estradiol, estrone, testosterone, dehydroepiandrosterone
      sulfate, sex hormone-binding globulin, a follicle-stimulating hormone, a
      luteinizing hormone, and prolactin among 393 premenopausal women who had regular
      menstrual cycles fewer than 40 days apart. The dietary intakes were estimated
      with a validated food frequency questionnaire. RESULTS: After controlling for
      age, BMI, phase of the menstrual cycle, number of births, age at first birth,
      history of breastfeeding, and smoking status, the saturated fat intake was
      significantly positively associated with total estradiol and free estradiol
      levels. Intakes of the other types of fat, dietary fiber, soy isoflavones, and
      alcohol were not significantly associated with levels of any hormone measured.
      CONCLUSIONS: These data suggest that a high intake of saturated fat is associated
      with increased estradiol levels in premenopausal Japanese women. Saturated fat
      intake may have implications in the etiology of breast cancer.

PMID- 22399235
TI  - Current and future anatomical and functional imaging approaches to
      pheochromocytoma and paraganglioma.
AB  - After establishing a biochemical diagnosis, pheochromocytomas and extra-adrenal
      paragangliomas (PPGLs) can be localized using different anatomical and functional
      imaging modalities. These include computed tomography, magnetic resonance
      imaging, single-photon emission computed tomography (SPECT) using 123I
      metaiodobenzylguanidine or 111In-DTPA-pentetreotide, and positron emission
      tomography (PET) using 6-[18F]-fluorodopamine (18F-FDA), 6-[18F]-fluoro-l-3,4
      dihydroxyphenylalanine (18F-DOPA), and 2-[18F]-fluoro-2-deoxy-d-glucose. We
      review the currently available data on the performance of anatomical imaging,
      SPECT, and PET for the detection of (metastatic) PPGL as well as parasympathetic
      head and neck paragangliomas. We show that there appears to be no 'gold-standard'
      imaging technique for all patients with (suspected) PPGL. A tailor-made approach
      is warranted, guided by clinical, biochemical, and genetic characteristics. In
      the current era of a growing number of PET tracers, PPGL imaging has moved beyond
      tumor localization towards functional characterization of tumors.

PMID- 22399237
TI  - Differential adipose tissue inflammatory state in obese nondiabetic Zucker fatty
      rats compared to obese diabetic zucker diabetic fatty rats.
AB  - Adipose tissue (AT) inflammation is linked to the pathogenesis of diabetes in
      obesity. Here, we compare the AT inflammatory state of 2 animal models of obesity
      and obesity plus diabetes, respectively. Obese nondiabetic ZF rats exhibited a
      trend towards increased proportions of CD11b positive cells in the adipose tissue
      stroma vascular fraction suggesting a state of increased AT inflammation compared
      to their lean littermates, but no alterations in systemic inflammatory
      parameters. In contrast, obese diabetic ZDF rats exhibited systemic as well as
      local AT inflammation with elevated levels of circulating Regulated upon
      Activation, Normal T-cell Expressed and Secreted Protein (Rantes), interleukin
      1beta (IL-1beta) and monocyte chemotactic protein 1 (MCP-1), and an increased
      infiltration of adipose tissue CD11b positive cells. Our data provide a novel
      phenotypic characterisation of 2 common metabolic animal models and suggest an
      association of obesity with local inflammation in adipose tissue, and an
      association of diabetes with local inflammation in adipose tissue plus systemic
      inflammation. AT inflammation in obesity might therefore initiate a process that
      above a certain limits finally results in systemic inflammation and diabetes.

PMID- 22399236
TI  - Evidence for a role of frataxin in pancreatic islets isolated from multi-organ
      donors with and without type 2 diabetes mellitus.
AB  - Frataxin (FXN) is a mitochondrial protein involved in iron metabolism and in the
      modulation of reactive oxygen and/or nitrogen species production. No information
      is currently available as for the role of frataxin in isolated human pancreatic
      islets. We studied islets from pancreases of multi-organ donors with (T2DM) and
      without (Ctrl) Type 2 diabetes mellitus. In these islets, we determined FXN gene
      and protein expression by qualitative and quantitative Real-Time RT-PCR,
      nitrotyrosine concentration, and insulin release in response to glucose
      stimulation (SI). FXN gene and protein were expressed in human islets, though the
      level of expression was much lower in T2DM islets. The latter also had lower
      insulin release and higher concentration of nitrotyrosine. A positive correlation
      was apparent between SI and FXN gene expression, while a negative correlation was
      found between nitrotyrosine islet concentration and FXN expression. Transfection
      of Ctrl islets with siRNA FXN caused reduction of FXN expression, increase of
      nitrotyrosine concentration, and reduction of insulin release. In conclusion, in
      human pancreatic islets FXN contributes to regulation of oxidative stress and
      insulin release in response to glucose. In islets from T2DM patients FXN
      expression is reduced while oxidative stress is increased and insulin release in
      response to glucose impaired.

PMID- 22399239
TI  - Novel endophytic yeast Rhodotorula mucilaginosa strain PTD3 I: production of
      xylitol and ethanol.
AB  - An endophytic yeast, Rhodotorula mucilaginosa strain PTD3, that was isolated from
      stems of hybrid poplar was found to be capable of production of xylitol from
      xylose, of ethanol from glucose, galactose, and mannose, and of arabitol from
      arabinose. The utilization of 30 g/L of each of the five sugars during
      fermentation by PTD3 was studied in liquid batch cultures. Glucose-acclimated
      PTD3 produced enhanced yields of xylitol (67% of theoretical yield) from xylose
      and of ethanol (84, 86, and 94% of theoretical yield, respectively) from glucose,
      galactose, and mannose. Additionally, this yeast was capable of metabolizing high
      concentrations of mixed sugars (150 g/L), with high yields of xylitol (61% of
      theoretical yield) and ethanol (83% of theoretical yield). A 1:1 glucose:xylose
      ratio with 30 g/L of each during double sugar fermentation did not affect PTD3's
      ability to produce high yields of xylitol (65% of theoretical yield) and ethanol
      (92% of theoretical yield). Surprisingly, the highest yields of xylitol (76% of
      theoretical yield) and ethanol (100% of theoretical yield) were observed during
      fermentation of sugars present in the lignocellulosic hydrolysate obtained after
      steam pretreatment of a mixture of hybrid poplar and Douglas fir. PTD3
      demonstrated an exceptional ability to ferment the hydrolysate, overcome hexose
      repression of xylose utilization with a short lag period of 10 h, and tolerate
      sugar degradation products. In direct comparison, PTD3 had higher xylitol yields
      from the mixed sugar hydrolysate compared with the widely studied and used
      xylitol producer Candida guilliermondii.

PMID- 22399238
TI  - The dopaminergic stabilizer pridopidine is to a major extent N-depropylated by
      CYP2D6 in humans.
AB  - PURPOSE: The influence of the cytochrome P450 enzyme CYP2D6 in the metabolism of
      the novel dopaminergic stabilizer pridopidine was investigated in healthy Swedish
      Caucasians. METHODS: Six extensive metabolizers (EM) and six poor metabolizers
      (PM) of debrisoquine were given a single oral dose of pridopidine (EM, 50 mg; PM,
      25 mg). RESULTS: The mean total plasma clearance of pridopidine was 541 and 138
      mL/min in EM and PM, respectively (p = 0.003), and was slightly higher in PM than
      the mean renal plasma clearance (105 mL/min; p = 0.11). The mean plasma area
      under the time-concentration curve between time zero and 32 h (AUC(0-32 h)) of
      the N-depropyl metabolite ACR30 was higher in EM than in PM (1,377 vs. 61 nmol
      h/mL, respectively; p < 0.001). The urinary excretion of pridopidine + ACR30 was
      high in both EM (85 %) and PM (78 %). The dose-adjusted peak concentration
      (C(max)) was not statistically different in EM and PM; consequently, the oral
      absorption of pridopidine was close to complete. CONCLUSIONS: Following a single
      dose of pridopidine, the drug is N-depropylated by CYP2D6 in EM, while in PM the
      most important elimination pathway is renal glomerular filtration. Results of
      studies examining the effects of multiple repeat dosing suggest that the CYP2D6
      enzyme is at least partly inactivated by pridopidine.

PMID- 22399234
TI  - Targeting pattern recognition receptors in cancer immunotherapy.
AB  - Pattern recognition receptors (PRRs) are known for many years for their role in
      the recognition of microbial products and the subsequent activation of the immune
      system. The 2011 Nobel Prize for medicine indeed rewarded J. Hoffmann/B. Beutler
      and R. Steinman for their revolutionary findings concerning the activation of the
      immune system, thus stressing the significance of understanding the mechanisms of
      activation of the innate immunity. Such immunostimulatory activities are of major
      interest in the context of cancer to induce long-term antitumoral responses.
      Ligands for the toll-like receptors (TLRs), a well-known family of PRR, have been
      shown to have antitumoral activities in several cancers. Those ligands are now
      undergoing extensive clinical investigations both as immunostimulant molecules
      and as adjuvant along with vaccines. However, when considering the use of these
      ligands in tumor therapy, one shall consider the potential effect on the tumor
      cells themselves as well as on the entire organism. Recent data indeed
      demonstrate that TLR activation in tumor cells could trigger both pro- or
      antitumoral effect depending on the context. This review discusses this balance
      between the intrinsic activation of PRR in tumor cells and the extrinsic
      microenvironment activation in term of overall effect of PRR ligands on tumor
      development. We review recent advances in the field and underline appealing
      prospects for clinical development of PRR agonists in the light of our current
      knowledge on their expression and activation.

PMID- 22399240
TI  - Lasiodiplodan, an exocellular (1->6)-beta-D: -glucan from Lasiodiplodia
      theobromae MMPI: production on glucose, fermentation kinetics, rheology and anti
      proliferative activity.
AB  - Lasiodiplodan, an exopolysaccharide of the (1->6)-beta-D: -glucan type, is
      produced by Lasiodiplodia theobromae MMPI when grown under submerged culture on
      glucose. The objective of this study was to evaluate lasiodiplodan production by
      examining the effects of carbon (glucose, fructose, maltose, sucrose) and
      nitrogen sources (KNO(3), (NH(4))(2)SO(4), urea, yeast extract, peptone), its
      production in shake flasks compared to a stirred-tank bioreactor, and to study
      the rheology of lasiodiplodan, and lasiodiplodan's anti-proliferative effect on
      breast cancer MCF-7 cells. Although glucose (2.05 +/- 0.05 g L(-1)), maltose
      (2.08 +/- 0.04 g L(-1)) and yeast extract (2.46 +/- 0.06 g L(-1)) produced the
      highest amounts of lasiodiplodan, urea as N source resulted in more lasiodiplodan
      per unit biomass than yeast extract (0.74 +/- 0.006 vs. 0.22 +/- 0.008 g g(-1)).
      A comparison of the fermentative parameters of L. theobromae MMPI in shake flasks
      and a stirred-tank bioreactor at 120 h on glucose as carbon source showed maximum
      lasiodiplodan production in agitated flasks (7.01 +/- 0.07 g L(-1)) with a
      specific yield of 0.25 +/- 0.57 g g(-1) and a volumetric productivity of 0.06 +/-
      0.001 g L(-1) h(-1). A factorial 2(2) statistical design developed to evaluate
      the effect of glucose concentration (20-60 g L(-1)) and impeller speed (100-200
      rpm) on lasiodiplodan production in the bioreactor showed the highest production
      (6.32 g L(-1)) at 72 h. Lasiodiplodan presented pseudoplastic behaviour, and the
      apparent viscosity increased at 60 degrees C in the presence of CaCl(2). Anti
      proliferative activity of lasiodiplodan was demonstrated in MCF-7 cells, which
      was time- and dose-dependent with an IC(50) of 100 MUg lasiodiplodan mL(-1).

PMID- 22399241
TI  - Lipofuscin accumulation and gene expression in different tissues of mnd mice.
AB  - Neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage diseases
      characterized by neurological impairment and blindness. NCLs are almost always
      due to single mutations in different genes (CLN1-CLN8). Ubiquitous accumulation
      of undigested material and of a hydrophobic inner mitochondrial membrane protein,
      the subunit c of mitochondrial ATP synthase, has been described. Although protein
      mutation(s) in the endoplasmic reticulum-lysosomes axis can modify the
      trafficking and the recycling of different molecules, one of the upstream targets
      in these diseases may be represented by the balance of gene expression. To
      understand if and how neurons modify the levels of important genes during the
      first phases of the disease, it is important to characterize the mechanisms of
      neurodegeneration. Due to the impossibility of performing this analysis in
      humans, alternative models of investigation are required. In this study, a mouse
      model of human NCL8, the mnd mouse has been employed. The mnd mice recapitulate
      many clinical and histopathological features described in NCL8 patients. In this
      study, we found an altered expression of different genes in both central and
      peripheral organs associated with lipopigment accumulation. This is a preliminary
      approach, which could also be of interest in providing new diagnostic tools for
      NCLs.

PMID- 22399242
TI  - The use of optical fiber in endodontic photodynamic therapy. Is it really
      relevant?
AB  - This study analyzed the necessity of use of an optical fiber/diffusor when
      performing antimicrobial photodynamic therapy (PDT) associated with endodontic
      therapy. Fifty freshly extracted human single-rooted teeth were used.
      Conventional endodontic treatment was performed using a sequence of ProTaper
      (Dentsply Maillefer Instruments), the teeth were sterilized, and the canals were
      contaminated with Enterococcus faecalis 3 days' biofilm. The samples were divided
      into five groups: group 1--ten roots irradiated with a laser tip (area of 0.04
      cm(2)), group 2--ten roots irradiated with a smaller laser tip (area of 0.028
      cm(2)), and group 3--ten teeth with the crown, irradiate with the laser tip with
      0.04 cm(2) of area. The forth group (G4) followed the same methodology as group
      3, but the irradiation was performed with smaller tip (area of 0.028 cm(2)) and
      G5 ten teeth with crown were irradiated using a 200-mm-diameter fiber/diffusor
      coupled to diode laser. Microbiological samples were taken after accessing the
      canal, after endodontic therapy, and after PDT. Groups 1 and 2 showed a reduction
      of two logs (99%), groups 3 and 4 of one log (85% and 97%, respectively), and
      group 5 of four logs (99.99%). Results suggest that the use of PDT added to
      endodontic treatment in roots canals infected with E. faecalis with the optical
      fiber/diffusor is better than when the laser light is used directed at the access
      of cavity.

PMID- 22399243
TI  - Effects of low-level laser therapy (GaAs) in an animal model of muscular damage
      induced by trauma.
AB  - It has been demonstrated that reactive oxygen species (ROS) formation and
      oxidative damage markers are increased after muscle damage. Recent studies have
      demonstrated that low-level laser therapy (LLLT) modulates many biochemical
      processes mainly those related to reduction of muscular injures, increment of
      mitochondrial respiration and ATP synthesis, as well as acceleration of the
      healing process. The objective of the present investigation was to verify the
      influence of LLLT in some parameters of muscular injury, oxidative damage,
      antioxidant activity, and synthesis of collagen after traumatic muscular injury.
      Adult male Wistar rats were divided randomly into three groups (n = 6), namely,
      sham (uninjured muscle), muscle injury without treatment, and muscle injury with
      LLLT (GaAs, 904 nm). Each treated point received 5 J/cm(2) or 0.5 J of energy
      density (12.5 s) and 2.5 J per treatment (five regions). LLLT was administered 2,
      12, 24, 48, 72, 96, and 120 h after muscle trauma. The serum creatine kinase
      activity was used as an index of skeletal muscle injury. Superoxide anion,
      thiobarbituric acid reactive substance (TBARS) measurement, and superoxide
      dismutase (SOD) activity were used as indicators of oxidative stress. In order to
      assess the synthesis of collagen, levels of hydroxyproline were measured. Our
      results have shown that the model of traumatic injury induces a significant
      increase in serum creatine kinase activity, hydroxyproline content, superoxide
      anion production, TBARS level, and activity of SOD compared to control. LLLT
      accelerated the muscular healing by significantly decreasing superoxide anion
      production, TBARS levels, the activity of SOD, and hydroxyproline content. The
      data strongly indicate that increased ROS production and augmented collagen
      synthesis are elicited by traumatic muscular injury, effects that were
      significantly decreased by LLLT.

PMID- 22399244
TI  - Iconicity of simple Chinese characters.
AB  - The iconicity of a Chinese character, or the degree to which it looks like the
      concept that it represents, has been suggested as affecting the learning and
      processing of the character. However, previous studies have not provided good
      empirical information on the iconicity of specific characters. To fill this gap,
      40 U.S. adults with no knowledge of Chinese were given an English word or short
      phrase together with two Chinese characters and were asked which character
      matched the meaning of the English word. The right and wrong answers had the same
      number of strokes, and different wrong answers were used for different
      participants. We examined all 213 simple-structure Chinese characters that occur
      in textbooks for elementary school children. The overall percentage of correct
      responses was 53.6%, slightly but significantly higher than would be expected by
      chance. Using a false discovery rate procedure, we found that 15 of the 213
      characters were guessed at a level higher than chance. The proportion of correct
      responses to each character, which can be taken as an indicator of its degree of
      iconicity, should be useful to researchers studying Chinese character reading and
      writing. The full database, showing the proportion of correct guesses and other
      psycholinguistic variables for each character, can be downloaded from
      http://brm.psychonomic-journals.org/content/supplemental .

PMID- 22399245
TI  - Using the linear mixed model to analyze nonnormal data distributions in
      longitudinal designs.
AB  - Using a Monte Carlo simulation and the Kenward-Roger (KR) correction for degrees
      of freedom, in this article we analyzed the application of the linear mixed model
      (LMM) to a mixed repeated measures design. The LMM was first used to select the
      covariance structure with three types of data distribution: normal, exponential,
      and log-normal. This showed that, with homogeneous between-groups covariance and
      when the distribution was normal, the covariance structure with the best fit was
      the unstructured population matrix. However, with heterogeneous between-groups
      covariance and when the pairing between covariance matrices and group sizes was
      null, the best fit was shown by the between-subjects heterogeneous unstructured
      population matrix, which was the case for all of the distributions analyzed. By
      contrast, with positive or negative pairings, the within-subjects and between
      subjects heterogeneous first-order autoregressive structure produced the best
      fit. In the second stage of the study, the robustness of the LMM was tested. This
      showed that the KR method provided adequate control of Type I error rates for the
      time effect with normally distributed data. However, as skewness increased-as
      occurs, for example, in the log-normal distribution-the robustness of KR was
      null, especially when the assumption of sphericity was violated. As regards the
      influence of kurtosis, the analysis showed that the degree of robustness
      increased in line with the amount of kurtosis.

PMID- 22399246
TI  - Life-saving decompressive craniectomy for acute disseminated encephalomyelitis in
      a child: a case report.

PMID- 22399247
TI  - Access to health care for undocumented migrant children and pregnant women: the
      paradox between values and attitudes of health care professionals.
AB  - Access to health care for undocumented migrant children and pregnant women
      confronts human rights and professional values with political and institutional
      regulations that limit services. In order to understand how health care
      professionals deal with these diverging mandates, we assessed their attitudes
      toward providing care to this population. Clinicians, administrators, and support
      staff (n = 1,048) in hospitals and primary care centers of a large multiethnic
      city responded to an online survey about attitudes toward access to health care
      services. Analysis examined the role of personal and institutional correlates of
      these attitudes. Foreign-born respondents and those in primary care centers were
      more likely to assess the present access to care as a serious problem, and to
      endorse broad or full access to services, primarily based on human rights
      reasons. Clinicians were more likely than support staff to endorse full or broad
      access to health care services. Respondents who approved of restricted or no
      access also endorsed health as a basic human right (61.1%) and child development
      as a priority (68.6%). A wide gap separates attitudes toward entitlement to
      health care and the endorsement of principles stemming from human rights and the
      best interest of the child. Case-based discussions with professionals facing
      value dilemmas and training on children's rights are needed to promote equitable
      practices and advocacy against regulations limiting services.

PMID- 22399248
TI  - Effect of mosapride citrate on gastric emptying in interferon-induced
      gastroparesis.
AB  - BACKGROUND AND OBJECTIVES: Gastroparesis, a gastrointestinal autonomic
      neuropathy, is a common adverse reaction in chronic hepatitis C (CHC) patients
      receiving interferon therapy. Current therapeutic options are limited. We
      evaluated the efficacy of mosapride for IFN-induced gastroparesis. METHODS:
      Twenty-four consecutive CHC patients were randomly assigned to either the control
      group, which received pegylated interferon alpha-2b at 1.5 MUg/kg/week and
      ribavirin at 600-1,000 mg/day, depending on body weight (PegIFN/RBV), or the
      mosapride group, which received PegIFN/RBV plus mosapride at 15 mg/person/day.
      The solid-phase gastric emptying half-times (T1/2) of the total, proximal, and
      distal stomach (scintigraphy) and digestive symptoms (questionnaire) were
      measured within one week before and four weeks after initiation of the assigned
      therapy. The test meal comprised a 200-g pancake containing Tc-99m
      diethylenetriamine pentaacetic acid. RESULTS: In the control group, after
      PegIFN/RBV initiation, a significant increase was observed in the total T1/2
      (before: 84.0 +/- 22.1 min versus after: 100.8 +/- 28.9 min, P = 0.03), the
      distal T1/2 (before: 95.3 +/- 32.2 min versus after: 115.3 +/- 41.4 min, P =
      0.03), and digestive symptom score (before: 3.2 +/- 1.4 versus after: 8.1 +/-
      4.8, P = 0.02); proximal T1/2 change was not significant. In the mosapride group,
      no significant delays were observed in the total, proximal, and distal T1/2
      values; the change in symptom scores was not significant. CONCLUSIONS: Mosapride
      improved total and distal gastric motility in IFN-induced gastroparesis, and
      consequently relieved symptoms.

PMID- 22399251
TI  - Treatment of fingertip amputation: comparison of results between microsurgical
      replantation and pocket principle.
AB  - In this article, a comparison of replantation using microsurgical replantation
      (replantation) and the Brent method and its modification (pocket principle) in
      the treatment of fingertip amputation is reported. As a classification of
      amputation level, we used Ishikawa's subzone classification of fingertip
      amputation, and the cases of amputations only in subzone 2 were included in this
      study. Between these two groups, there was no statistical difference in survival
      rate, postoperative atrophy, or postoperative range of motion. In terms of
      sensory recovery, some records were lost and exact study was difficult. But there
      was no obvious difference between these cases. In our comparison of microsurgical
      replantation versus the pocket principle in treatment of subzone 2 fingertip
      amputation, there was no difference in postoperative results. Each method has
      pros and cons, and the surgeon should choose which technique to use based on his
      or her understanding of the characteristics of both methods.

PMID- 22399249
TI  - Adenovirus-mediated dual gene expression of human interleukin-10 and hepatic
      growth factor exerts protective effect against CCl4-induced hepatocyte injury in
      rats.
AB  - BACKGROUND: Hepatocyte injury is a common pathological cause of various liver
      diseases. Due to a lack of an effective preventive treatment, gene therapy has
      become an interesting approach to prevent and alleviate liver injury. AIMS: A
      protective effect of adenovirus-mediated dual gene expression of human
      interleukin-10 (hIL-10) and human hepatocyte growth factor (hHGF) was
      investigated against tetrachloromethane (CCl(4))-induced hepatocyte injury in
      rats. METHODS: An adenoviral vector carrying the hIL-10 and hHGF genes was
      constructed, and its protective effect against rat hepatocyte injury was
      investigated both in vivo and in vitro. RESULTS: In the in vitro CCl(4)-induced
      cell injury model, simultaneous transfection of hIL-10 and hHGF genes via an
      adenoviral vector resulted in production of anti-hepatocyte biological factors by
      an autocrine mechanism, then significantly improved hepatocyte viability. In the
      in vivo rat model, synergistic effects of these two gene products protected
      hepatocytes from damage by reducing the CC1(4)-induced hepatocyte degeneration,
      hepatic fibrosis, and intrahepatic inflammatory cell infiltration, thereby
      preserving liver function. CONCLUSION: Adenovirus-mediated dual gene expression
      of hIL-10 and hHGF effectively protected against liver damage by likely
      regulating immune responses to reduce hepatocyte injury and by promoting
      hepatocyte regeneration. The hIL-10 and hHGF dual gene expression vector has
      significant potential in the field of liver disease therapeutics and constitutes
      one of the most promising current strategies for gene therapy.

PMID- 22399250
TI  - Family planning use among urban poor women from six cities of Uttar Pradesh,
      India.
AB  - Family planning has widespread positive impacts for population health and well
      being; contraceptive use not only decreases unintended pregnancies and reduces
      infant and maternal mortality and morbidity, but it is critical to the
      achievement of Millennium Development Goals. This study uses baseline,
      representative data from six cities in Uttar Pradesh, India to examine family
      planning use among the urban poor. Data were collected from about 3,000 currently
      married women in each city (Allahabad, Agra, Varanasi, Aligarh, Gorakhpur, and
      Moradabad) for a total sample size of 17,643 women. Participating women were
      asked about their fertility desires, family planning use, and reproductive
      health. The survey over-sampled slum residents; this permits in-depth analyses of
      the urban poor and their family planning use behaviors. Bivariate and
      multivariate analyses are used to examine the role of wealth and education on
      family planning use and unmet need for family planning. Across all of the cities,
      about 50% of women report modern method use. Women in slum areas generally report
      less family planning use and among those women who use, slum women are more
      likely to be sterilized than to use other methods, including condoms and hormonal
      methods. Across all cities, there is a higher unmet need for family planning to
      limit childbearing than for spacing births. Poorer women are more likely to have
      an unmet need than richer women in both the slum and non-slum samples; this
      effect is attenuated when education is included in the analysis. Programs seeking
      to target the urban poor in Uttar Pradesh and elsewhere in India may be better
      served to identify the less educated women and target these women with
      appropriate family planning messages and methods that meet their current and
      future fertility desire needs.

PMID- 22399252
TI  - Lower extremity reconstruction with the anterolateral thigh flap.
AB  - The versatility and location of the anterolateral thigh (ALT) flap make it well
      suited for lower extremity reconstruction. The purpose of this study was to
      evaluate surgical and functional outcomes by specific anatomic regions in the
      lower extremity to better define the role of the ALT flap in lower extremity
      reconstruction. A retrospective review of patients undergoing lower extremity
      reconstruction with an ALT flap between July 2002 and December 2010 was
      performed. Total 46 patients underwent lower extremity reconstruction with an ALT
      flap, of whom 29 (63%) had a pedicled flap and 17 (37%) a microvascular free
      flap. Defects were located in the hip/buttocks (n = 8), groin (n = 13), thigh (n
      = 8), knee (n = 5), leg (n = 6), and foot/ankle (n = 6). The mean postoperative
      follow-up was 4 months. Total flap loss occurred in two patients (4%). There were
      11 recipient site complications (24%). The most common complication was recipient
      site seroma, which occurred in five patients (11%), all of whom had hip/buttock
      or groin defects. Overall, 38 patients (83%) returned to their preoperative
      functional status. The ALT flap is an effective method of lower extremity
      reconstruction. It can be performed as a pedicled or free flap, with good
      surgical and functional outcomes.

PMID- 22399253
TI  - Selection of recipient vessel in traumatic lower extremity.
AB  - The main focus of this paper is the selection of proper vessels for successful
      free tissue transfer in lower extremities which have suffered extensive trauma.
      The selection of proper recipient vessels for traumatized lower extremities still
      presents difficulties for surgeons. This review will provide a general guideline
      for the selection of proper recipient vessels in traumatic lower extremity
      reconstruction and describe the possible reasons why some recipient vessels
      present more problems than others.

PMID- 22399254
TI  - Free tensor fasciae latae flap for abdominal wall reconstruction: overview and
      new innovation.
AB  - Extensive abdominal wall defects may result from tumor extirpation, traumatic
      injury, or soft tissue infections. Extensive traumatic injuries can often disrupt
      the soft tissue content of the abdomen as well as the bony support provided by
      the pelvis. Reconstruction of the lower abdomen should aim to recreate dynamic
      stability. Five patients with extensive lower abdominal wall disruption following
      traumatic injuries or infection were treated using a novel flap for functional
      reconstruction. We devised a free neurotized osteomyocutaneous tensor fasciae
      latae (TFL) flap that would restore bony continuity by providing a vascularized
      bone graft and simultaneously maintain the integrity of the attachment of the
      tensor fascia latae muscle to the iliac crest, reestablishing musculofascial
      continuity. A branch of the superior gluteal nerve was harvested with this
      composite flap and coapted to an intercostal nerve for reinnervation, thereby
      creating a dynamic muscle in these patients. All patients underwent successful
      free tissue reconstruction with 100% flap survival. The lower abdominal wall and
      bony integrity of the pelvis were successfully reconstructed. Reinnervation has
      shown clinical signs of maintained dynamic stability. The innervated TFL
      osteomyocutaneous flap is an ideal option for lower abdominal reconstruction in
      patients with complex abdominoperineal defects with loss of bony integrity.

PMID- 22399255
TI  - Advanced MR neurography imaging of radial nerve entrapment at the spiral groove:
      a case report.
AB  - High-resolution magnetic resonance neurography (MRN) is being increasingly
      employed for the evaluation of peripheral nerves. We describe a case of spiral
      groove syndrome (Saturday night palsy) and illustrate the role of advanced 3
      Tesla MRN imaging techniques, including three-dimensional diffusion-weighted fat
      suppressed reversed fast imaging with steady-state precession and diffusion
      tensor imaging.

PMID- 22399256
TI  - Hands-free suction in microsurgery.

PMID- 22399257
TI  - Reconstruction after robotic head and neck surgery: when and why.
AB  - The advancement of robotically assisted surgery during the last decade has seen a
      revolution in the approach to surgical oncologic resection, moving toward
      reducing patient morbidity without compromising oncologic outcomes. In no field
      has this been more dramatic than in the application of transoral robotic surgery
      (TORS), using the da Vinci surgical system for resecting tumors of the head and
      neck. This organ-preserving technique allows the surgeon to remove tumors of the
      upper aerodigestive tract without external incisions and potentially spare the
      patient adjuvant treatment. The introduction of TORS improves upon current
      transoral techniques to the oropharynx and supraglottis. The traditional
      conception of TORS is that it would be used for smaller tumors and defects would
      be permitted to heal by secondary intention; however, as head and neck surgeons
      pursue larger tumors robotically, robotic-assisted reconstruction has entered the
      paradigm. Given the relative infancy of these procedures, clear guidelines for
      when reconstruction is warranted do not exist. The current literature, thus far,
      has focused on feasibility, safety, and implement of the robot in reconstruction.
      We reviewed the current literature pertinent to TORS reconstruction focusing on
      patient selection, tumor size, and location. Furthermore, we briefly review our
      own experience of 20 TORS procedures involving robotic-assisted reconstructions.
      Finally, we provide an algorithmic approach to determining the need for
      reconstruction in a given patient. This focuses on four key criteria: tumor
      location, tumor extent, prior treatment, and patient-specific factors.

PMID- 22399258
TI  - Technical recommendations for penile replantation based on lessons learned from
      penile reconstruction.
AB  - Penile amputation is an exceptional surgical emergency. Immediate replantation
      yields a high success and low complication rate. We report a case of a self
      inflicted penile amputation treated with successful microsurgical replantation.
      Postoperative edema caused minor skin slough and temporary venous congestion was
      treated with medicinal leech therapy. Follow-up at 18 months showed normal
      subjective sensation; voiding and erectile function were present. Surgical
      management and technique refinements are discussed, based on a review of the
      literature and on our experience in penile reconstruction.

PMID- 22399259
TI  - Phasic changes in cell proliferation in an autogenous vein graft used to repair
      the lacrimal canaliculus in a rabbit model.
AB  - There are few reports that describe the physiological changes in a vein graft
      used to reconstruct lacrimal canaliculus. This article aims to observe the phasic
      changes in cell proliferation in an autogenous vein graft used to repair the
      lacrimal canaliculus. Lacrimal canaliculus disjunction was made in a rabbit model
      by transecting one side of the lacrimal canaliculus. The injury was repaired
      using an autogenous ear vein graft. Phasic changes in cell proliferation were
      observed using reverse transcription polymerase chain reaction and
      immunohistochemistry for the expression of proliferating cell nuclear antigen in
      the grafted vein segment. At 3 days postoperative, cell proliferation in the
      grafted vein segment became active, peaking at 7 days postoperative. Cell
      proliferation became stable in the epithelium, but remained active in the
      subepithelial connective tissue at 28 days postoperative. The phasic changes in
      cell proliferation in the autogenous vein graft were consistent with a normal
      wound healing response.

PMID- 22399261
TI  - Distribution and population estimate for the chacma baboon (Papio ursinus) in
      KwaZulu-Natal, South Africa.
AB  - We report the current species distribution and population estimate for the chacma
      baboon (Papio ursinus) in KwaZulu-Natal Province (KZN), South Africa, based on an
      analysis of estimated area of occupancy and estimated home range size. This
      estimate suggests a total population size of approximately 11,000 individuals for
      KZN. Much of the province is uninhabited, with a density in occupied areas of
      approximately 1.8 animals per km(2). The current population size may be more than
      an order of magnitude smaller than historical population size. Chacma baboons now
      exhibit a highly fragmented and discontinuous distribution in KZN, with 58% of
      the population residing within protected areas, and more than half of these
      troops reside in areas >1,500 m above average sea level. The small population and
      highly fragmented distribution of chacma baboons in KZN, combined with rapidly
      increasing human population size and transformation of natural habitat, suggest
      this species requires greater conservation attention.

PMID- 22399262
TI  - The quest for transplantation tolerance: have we finally sipped from the cup?
AB  - New advances in achieving hematopoietic chimerism may facilitate immunological
      tolerance to kidney transplants.

PMID- 22399260
TI  - Cl anion-dependent Mg-ATPase.
AB  - We studied, in the rat brain, the synaptosomal and microsomal membrane fractions
      of Cl- ion-activated, Mg2+-dependent ATPase, satisfying the necessary kinetic
      peculiarities of transport ATPases, by a novel method of kinetic analysis of the
      multisite enzyme systems: (1) the [Mg-ATP] complex constitutes the substrate of
      the enzymic reaction; (2) the V = f(Cl-) dependence-reflecting curve is bell
      shaped; (3) substrate dependence, V = f(S), curves at a constant concentration of
      free ligands (Mg(f), ATP(f), Cl-); (4) as known from the literature, in the
      process of reaction a phosphorylated intermediate is formed (Gerencser, Crit Rev
      Biochem Mol Biol 31:303-337, 1996). We report on the Cl-ATPase molecular
      mechanism and its place in the "P-type ATPase" classification.

PMID- 22399263
TI  - Impersonalized medicine.
AB  - Research reported in this issue of Science Translational Medicine illustrates the
      benefits of short-term food withdrawal (fasting) in the treatment of cancer.
      Fasting exploited fundamental differences in the way tumor cells and normal cells
      respond to stress, simultaneously strengthening normal cell function and
      weakening tumor cell survival in the presence of toxic doses of chemotherapeutic
      drugs.

PMID- 22399264
TI  - Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched
      combined kidney and hematopoietic stem cell transplantation.
AB  - The toxicity of chronic immunosuppressive agents required for organ transplant
      maintenance has prompted investigators to pursue approaches to induce immune
      tolerance. We developed an approach using a bioengineered mobilized cellular
      product enriched for hematopoietic stem cells (HSCs) and tolerogenic graft
      facilitating cells (FCs) combined with nonmyeloablative conditioning; this
      approach resulted in engraftment, durable chimerism, and tolerance induction in
      recipients with highly mismatched related and unrelated donors. Eight recipients
      of human leukocyte antigen (HLA)-mismatched kidney and FC/HSC transplants
      underwent conditioning with fludarabine, 200-centigray total body irradiation,
      and cyclophosphamide followed by posttransplant immunosuppression with tacrolimus
      and mycophenolate mofetil. Subjects ranged in age from 29 to 56 years. HLA match
      ranged from five of six loci with related donors to one of six loci with
      unrelated donors. The absolute neutrophil counts reached a nadir about 1 week
      after transplant, with recovery by 2 weeks. Multilineage chimerism at 1 month
      ranged from 6 to 100%. The conditioning was well tolerated, with outpatient
      management after postoperative day 2. Two subjects exhibited transient chimerism
      and were maintained on low-dose tacrolimus monotherapy. One subject developed
      viral sepsis 2 months after transplant and experienced renal artery thrombosis.
      Five subjects experienced durable chimerism, demonstrated immunocompetence and
      donor-specific tolerance by in vitro proliferative assays, and were successfully
      weaned off all immunosuppression 1 year after transplant. None of the recipients
      produced anti-donor antibody or exhibited engraftment syndrome or graft-versus
      host disease. These results suggest that manipulation of a mobilized stem cell
      graft and nonmyeloablative conditioning represents a safe, practical, and
      reproducible means of inducing durable chimerism and donor-specific tolerance in
      solid organ transplant recipients.

PMID- 22399265
TI  - DNA-protein interactions: methods for detection and analysis.
AB  - DNA-binding proteins control various cellular processes such as recombination,
      replication and transcription. This review is aimed to summarize some of the most
      commonly used techniques to determine DNA-protein interactions. In vitro
      techniques such as footprinting assays, electrophoretic mobility shift assay,
      southwestern blotting, yeast one-hybrid assay, phage display and proximity
      ligation assay have been discussed. The highly versatile in vivo techniques such
      as chromatin immunoprecipitation and its variants, DNA adenine methyl transferase
      identification as well as 3C and chip-loop assay have also been summarized. In
      addition, some in silico tools have been reviewed to provide computational basis
      for determining DNA-protein interactions. Biophysical techniques like
      fluorescence resonance energy transfer (FRET) techniques, FRET-FLIM, circular
      dichroism, atomic force microscopy, nuclear magnetic resonance, surface plasmon
      resonance, etc. have also been highlighted.

PMID- 22399267
TI  - Response to letter to the editor: Reflux esophagitis and marginal ulcer after
      pancreaticoduodenectomy.

PMID- 22399266
TI  - Effect of simvastatin on the osteogenetic behavior of alveolar osteoblasts and
      periodontal ligament cells.
AB  - Statins are routinely used in the clinic as cholesterol lowering drugs, but
      recently they were reported to also have anabolic effects on bone tissue. Since
      regeneration of alveolar bone is one of the primary aims of periodontal
      treatment, in the present study we investigated the effects of simvastatin, a
      lipophilic statin, on primary alveolar osteoblasts (AOBs) and periodontal
      ligament cells (PDLs) in vitro. The effect of simvastatin (1-100 nM) on the cells
      proliferation/viability after 24, 48, and 72 h stimulation was measured using
      3,4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT)-assay. The
      alkaline phosphatase (ALP) activity was measured after stimulation with
      simvastatin using specific colorimetric assay. Finally, the mRNA expression
      levels of osteocalcin (OC), receptor activator of NF-kappaB ligand (RANKL), and
      osteoprotegerin (OPG) were measured by real-time PCR. The proliferation/viability
      of AOBs was significantly decreased by all simvastatin concentrations after 72 h
      stimulation. The proliferation/viability of PDLs was not influenced by
      simvastatin. ALP activity of AOBs and PDLs was increased by 1 and 100 nM
      simvastatin, respectively. Simvastatin induced a dose-dependent increase in OC
      mRNA expression of AOBs and did not influence that in PDLs. RANKL expression of
      AOBs was increased at all tested simvastatin concentrations and that in PDLs was
      increased by higher simvastatin concentrations (10-100 nM). Finally, the
      expression of OPG in AOBs and PDLs was stimulated by 1-10 and 100 nM simvastatin,
      respectively. Simvastatin seems to slightly increase the expression of osteogenic
      markers in AOBs and PDLs, indicating its ability to influence alveolar bone
      formation and periodontal regeneration.

PMID- 22399268
TI  - Staying alive: strategies for accountable health care.
AB  - The Patient Protection and Affordable Care Act signed into law in March 2010, has
      led to sweeping changes to the US health care system. The ensuing pace of change
      in health care regulation is unparalleled and difficult for physicians to keep up
      with. Because of the extraordinary challenges that have arisen, the public policy
      committee of the Society for Surgery of the Alimentary tract conducted a
      symposium at their 52nd Annual Meeting in May 2011 to educate participants on the
      myriad of public policy changes occurring in order to best prepare them for their
      future. Expert speakers presented their views on policy changes affecting diverse
      areas including patient safety, patient experience, hospital and provider fiscal
      challenges, and the life of the practicing surgeon. In all areas, surgical
      leadership was felt to be critical to successfully navigate the new health care
      landscape as surgeons have a long history of providing safe, high quality, low
      cost care. The recognition of shared values among the diverse constituents
      affected by health care policy changes will best prepare surgeons to control
      their own destiny and successfully manage new challenges as they emerge.

PMID- 22399269
TI  - Distal pancreatectomy with en bloc celiac axis resection for locally advanced
      pancreatic adenocarcinoma following neoadjuvant therapy.
AB  - BACKGROUND: Celiac trunk encasement by adenocarcinoma of the pancreatic body is
      generally regarded as a contraindication for surgical resection. Recent studies
      have suggested that a subset of stage III patients will succumb to their disease
      in the absence of distant metastases. We hypothesized that patients with stage
      III tumors invading the celiac trunk, who are free of distant disease following
      neoadjuvant therapy, may derive prolonged survival benefit from aggressive
      surgical resection. METHODS: We performed a retrospective review of distal
      pancreatectomies with en bloc celiac axis resection for pancreatic
      adenocarcinoma. RESULTS: Eleven patients underwent a distal pancreatectomy with
      en bloc celiac axis resection after completing neoadjuvant chemoradiation
      therapy. Median operative time was 8 h, 14 min, and median estimated blood loss
      was 700 ml. Median length of stay was 9 days. Five patients (45%) had
      postoperative complications; three were Clavien grade I. Four patients (35%) had
      pancreatic leaks; two were ISGPF grade B, and two were grade A. There were two 90
      day perioperative deaths. Ten patients had R0 resections (91%). After a median
      follow-up of 41 weeks, six patients recurred. Four of the five patients with
      SMAD4 loss recurred, and two of the five patients with intact SMAD4 recurred.
      Median disease-free and overall survival were 21 weeks and 26 months,
      respectively. CONCLUSIONS: Resection of pancreatic body adenocarcinoma with
      celiac axis resection is technically feasible with acceptable perioperative
      morbidity and mortality.

PMID- 22399270
TI  - Resection of tumors of the neck of the pancreas with venous invasion: the
      "Whipple at the Splenic Artery (WATSA)" procedure.
AB  - INTRODUCTION: Tumors of the neck of the pancreas may involve the superior
      mesenteric and portal veins as well as the termination of the splenic vein. This
      presents a difficult problem since the pancreas cannot be transected through the
      neck as is standard in a Whipple procedure. Here, we present our method of
      resecting such tumors, which we term "Whipple at the Splenic Artery (WATSA)".
      METHODS: The superior mesenteric and portal veins are isolated below and above
      the pancreas, respectively. The pancreas and splenic vein are divided just to the
      right of the point that the splenic artery contacts the superior border of the
      pancreas. This plane of transection is approximately 2 cm to the left of the
      pancreatic neck and away from the tumor. The superior mesenteric artery is
      cleared from the left side of the patient. With the specimen remaining attached
      only by the superior mesenteric and portal veins, these structures are clamped
      and divided. Reconstruction is performed with or without a superficial femoral
      vein graft. The splenic vein is not reconstructed. RESULTS: Ten cases have been
      performed to date without mortality. We have previously shown that the pattern of
      venous collateral development following occlusion of the termination of the
      splenic vein in the manner described is not similar to that of cases of sinistral
      (left sided) portal hypertension. DISCUSSION: Whipple at the splenic artery
      (WATSA) is a safe method for resection of tumors of the neck of the pancreas with
      vein involvement. It should be performed in high-volume pancreatic surgery
      centers.

PMID- 22399273
TI  - Paeoniae radix reduces PDGF-stimulated hepatic stellate cell migration.
AB  - Hepatic stellate cells (HSCs) play a key role in the pathogenesis of liver
      fibrosis. In chronic liver injury, HSCs undergo transdifferentiation to an
      activated myofibroblastic phenotype and migrate to injured areas in response to
      chemotactic factors, producing extracellular matrix proteins such as collagen
      type I to repair the damage as well as overexpression of alpha-smooth muscle
      actin (alpha-SMA). Paeoniae Radix, the root of Paeonia lactiflora Pall, was
      investigated for PDGF-BB-induced HSC chemotaxis. Rat HSCs and LX-2, a human HSC
      cell line, were used for the in vitro experiments. Cell migration was analyzed by
      wound-healing and transwell assays. An ELISA and a Sircol collagen assay kit were
      used to detect the expressions of alpha-SMA and of collagen, respectively.
      Phosphorylations of mitogen-activated protein kinases, including ERK 1/2, p38,
      and JNK, were evaluated with immunoblotting. Results indicated that PDGF-BB
      increased migration as well as alpha-SMA and collagen expression in HSCs.
      Paeoniae Radix extracts and its active components, paeonol and 1,2,3,4,6-penta- O
      galloyl- beta-D-glucose (PGG), inhibited PDGF-BB-induced HSC migration and alpha
      SMA and collagen expressions in a concentration-dependent manner. The inhibitory
      effects were associated with downregulation of PDGF receptor- alpha, ERK, p38,
      and JNK activation. Both paeonol and PGG participate in HSC migration, but via
      differential mechanisms.

PMID- 22399271
TI  - Body mass index and survival in esophageal adenocarcinoma treated with
      chemoradiotherapy followed by esophagectomy.
AB  - BACKGROUND: Body mass index (BMI) has been linked with inferior outcomes in
      gastrointestinal malignancies. The purpose of this study is to evaluate the
      effect of BMI on survival in patients with esophageal adenocarcinoma. METHODS:
      Medical records were analyzed for patients who underwent esophagectomy after
      neoadjuvant chemoradiotherapy (nCRT) for adenocarcinoma from 2000 to the present.
      Patients were grouped into BMI <= 25, >25-30, >30-35, and BMI >35. Overall
      survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan
      Meier method. Multivariate analysis (MVA) was performed using Cox proportional
      hazard regression model. RESULTS: We identified 303 patients for the analysis.
      The only difference in patient characteristics between groups was gender. We
      found no difference in OS and DFS associated with BMI (p=0.3297 for OS; p=0.5950
      for DFS). There were no differences in postoperative complications or mortality
      between BMI groups. MVA revealed that higher stage and less than a complete
      response to nCRT were prognostic for worse OS and DFS, while age, gender, type of
      surgery, year of diagnosis, and BMI were not prognostic. CONCLUSIONS: BMI was
      neither associated with surgical complications nor survival in patients with
      esophageal adenocarcinoma treated with nCRT. BMI should not be considered a
      contraindication to surgical resection after nCRT.

PMID- 22399274
TI  - Solasodine rhamnosyl glycosides cause apoptosis in cancer cells. Do they also
      prime the immune system resulting in long-term protection against cancer?
AB  - Solasodine rhamnosyl glycosides (SRGs) induce apoptosis in a wide variety of
      cancer cells and are more effective than many well-established anticancer agents.
      Combination therapy of SRGs with cisplatin treats cisplatin-resistant cells such
      as lung cancer and breast cancer cells. Anticancer therapies with SRGs have been
      used intravenously, intraperitoneally, intralesionally, orally, and topically.
      Data is now presented that in addition to apoptosis and, perhaps as a consequence
      thereof, SRGs also have an effect of stimulating lasting immunity against cancer
      as shown with a mouse model and the terminal cancer Sarcoma 180. Mice were
      inoculated i. p. with Sarcoma 180. Groups of animals were administered SRGs half
      an hour after Sarcoma 180 inoculation. Mice treated with Sarcoma 180 but not with
      SRGs all died within 20 days. Four doses of SRGs caused total remission of
      Sarcoma 180 activity. Mice that went into remission were then reinoculated 20
      days later with the cancer. Ten of twelve SRGs cured-animals were resistant to
      reinduction of terminal doses of the cancer. In comparison, twelve of twelve mice
      treated with SRGs without initial Sarcoma 180 activity but which were inoculated
      with Sarcoma 180 cells 20 days later, all died. In addition to apoptosis, SRGs
      stimulate lasting immunity against cancer. SRGs could play an important role in
      clinical management of diseases such a malignancy and also be used as a
      preventative therapy.

PMID- 22399275
TI  - Manganese chloride tetrahydrate (CMC-001) enhanced liver MRI: evaluation of
      efficacy and safety in healthy volunteers.
AB  - OBJECT: To evaluate the efficacy of three dose levels of the oral hepatobiliary
      manganese-based magnetic resonance imaging (MRI) contrast agent CMC-001, and
      assess its safety profile and patient acceptability. MATERIALS AND METHODS: After
      ethics committee approval, 32 healthy volunteers (males/females: 18/14) were
      included. Liver MRI was performed before and 3 h after ingestion of 0.8, 0.4, and
      0.2 g of CMC-001 on separate occasions. Liver-to-muscle signal intensity (SI)
      ratio from baseline to post-contrast and image quality was assessed. Adverse drug
      reactions/adverse events (ADRs/AEs) and clinico-laboratory tests were monitored.
      RESULTS: The increase in liver-to-muscle SI ratio was significantly higher after
      0.8 g (0.696) compared to 0.4 g (0.458) and 0.2 g (0.223) (in all pair-wise
      comparisons, P < 0.0001). The overall image quality was superior after 0.8 g.
      ADRs/AEs were dose-related and predominantly of mild intensity. CONCLUSION: Liver
      MRI using 0.8 g CMC-001 has the highest efficacy and still acceptable ADRs and
      should therefore be preferred.

PMID- 22399276
TI  - Synergistic tonic and phasic activity of the locus coeruleus norepinephrine (LC
      NE) arousal system is required for optimal attentional performance.
AB  - A certain level of arousal is required for an individual to perform optimally,
      and the locus coeruleus norepinephrine (LC-NE) system plays a central role in
      optimizing arousal. Tonic firing of LC-NE neurons needs to be held within a
      narrow range of 1-3 Hz to facilitate phasic firing of the LC-NE neurons; these
      two modes of activity act synergistically, to allow the individual to perform
      attentional tasks optimally. How this information can be applied to further our
      understanding of psychiatric disorders has not been fully elucidated. Here we
      propose two models of altered LC-NE activity that result in attentional deficits
      characteristic of psychiatric disorders: 1) 'hypoaroused' individuals with e.g.
      attention-deficit/hyperactivity disorder (ADHD) have decreased tonic firing of
      the LC-NE system, resulting in decreased cortical arousal and poor attentional
      performance and 2) 'hyperaroused' individuals with e.g. anxiety disorders have
      increased tonic firing of the LC-NE system, resulting in increased cortical
      arousal and impaired attentional performance. We argue that hypoarousal
      (decreased tonic firing of LC-NE neurons) and hyperarousal (increased tonic
      firing of LC-NE neurons) are suboptimal states in which phasic activity of LC-NE
      neurons is impeded. To further understand the neurobiology of attentional
      dysfunction in psychiatric disorders a translational approach that integrates
      findings on the LC-NE arousal system from animal models and human imaging studies
      may be useful.

PMID- 22399277
TI  - Comparative effectiveness of two self-collected sample kit distribution systems
      for chlamydia screening on a university campus.
AB  - OBJECTIVES: Chlamydia trachomatis (CT) rates and incidence continue to increase,
      and university students are known to engage in high-risk activities, but studies
      of CT prevalence in this population are limited by poor screening rates.
      Utilisation of self-obtained sample (SoS) kits in private student residencies may
      reduce screening barriers. The authors sought to determine the relative
      effectiveness, and comparative effectiveness, of two SoS kit distribution
      mechanisms: one which provided kits directly to students and another encouraging
      students to order kits from a website. METHODS: During 2010-2011, residents of
      six university dormitories were provided training sessions describing CT, the
      project and SoS kit use. Students in three dormitories were provided kits, and
      the remaining students directed to the website (http://www.iwantthekit.org).
      RESULTS: Of 391 resident students, 163 were provided with kits and 175 were
      directed to the website. Of provided kits, 12 (8 women) were returned and 2
      (16.7%; both women) were positive. Of only three internet-requested kits, all
      were returned (all women) and none were positive. In a post-project survey
      examining non-participation, 26.2% of students were unaware of the project (no
      difference by dormitory or gender) and 58.5% of women cited prior testing as part
      of a medical exam. CONCLUSIONS: Though direct kit distribution was more effective
      in student screening engagement, overall participation was poor despite
      widespread advertising. The methodology of online testing and SoS kits has been
      well validated elsewhere, but research is needed to successfully engage
      university students in screening and refine SoS target populations in light of
      changing healthcare policies.

PMID- 22399278
TI  - Compliance and efficacy of titratable thermoplastic versus custom mandibular
      advancement devices.
AB  - OBJECTIVE: To share our experiences treating patients with obstructive sleep
      apnea-hypopnea syndrome (OSAHS) with titratable thermoplastic (TPD) and custom
      made mandibular advancement devices (MAD) and to compare these devices in terms
      of objective improvement and cure and treatment success (improvement/cure plus
      adherence at 6 months). STUDY DESIGN: Case series with planned data collection.
      SETTING: Tertiary care center. SUBJECTS AND METHODS: Patients with OSAHS who
      failed or refused both continuous positive airway pressure (CPAP) and surgery had
      a titratable oral appliance fitted. Patients were offered an office-fitted TPD or
      a custom-made dentist-fitted device. Assessment included pretreatment and
      appliance-titration polysomnography (PSG). Improvement was defined as >= 50%
      apnea-hypopnea index (AHI) reduction plus posttreatment AHI <20, and cure was
      defined as AHI <5. Patients were contacted at 1 and 6 months regarding treatment
      adherence. RESULTS: A total of 180 patients (123 TPD, 57 custom) with complete
      PSG data were reviewed. Improvement/cure were significantly better with the
      custom device overall (91.2%/71.9% vs 77.2%/52.0%, P = .024/.012). Adherence data
      at 1 and 6 months were obtained from 128/180 and 119/180 patients, respectively.
      Using an intention-to-treat analysis, those lost to follow-up were considered
      nonadherent. Adherence at 1/6 months was 64.9%/50.9% for custom versus
      53.7%/32.5% for TPD (P = .156/.018), yielding treatment success rates (with
      initial improvement/cure) of 49.1%/40.4% for custom versus 27.6%/17.1% for TPD (P
      = .005/<.001) at 6 months. CONCLUSION: Custom-fit devices achieve higher rates of
      objective improvement and cure of OSAHS than TPD at the time of titration-PSG.
      TPDs have a high acceptance rate, low cost, and reasonable initial improvement
      and cure rates of 77.2% and 52.0%, respectively, but significantly poorer 6-month
      compliance.

PMID- 22399279
TI  - Sentinel node biopsy for head and neck desmoplastic melanoma: not a given.
AB  - OBJECTIVES: Determine the frequency of, the characteristics predictive of, and
      potential associated survival benefit from sentinel lymph node biopsy in a
      population of patients with desmoplastic melanoma of the head and neck. STUDY
      DESIGN: Analysis of a national database. SETTING: The 17-registry Surveillance,
      Epidemiology, and End Results (SEER) database. SUBJECTS AND METHODS: Using the
      SEER database, the authors identified patients diagnosed with cutaneous
      desmoplastic melanoma of the head and neck between 2003 and 2007. Nodal
      metastasis and impact of sentinel lymph node biopsy on survival were determined.
      RESULTS: The authors identified 467 cases of desmoplastic melanoma. Although most
      were locally advanced (median Breslow depth 3.5 mm), few had regional lymph node
      metastases (3.4%) or distant spread (3.2%) at the time of initial management. Of
      165 patients who had sentinel lymph node biopsy, 5% had positive regional lymph
      nodes. Breslow depth, ulceration, age, and sex were not predictive of positive
      sentinel lymph node biopsy. Patients who had sentinel lymph node biopsy did not
      have different cause-specific survival from those who did not undergo sentinel
      lymph node biopsy. CONCLUSION: Positive sentinel lymph node biopsies are rare in
      patients with desmoplastic melanoma of the head and neck. The low (5%) incidence
      of positive sentinel lymph node biopsy, coupled with the absence of identifiable
      survival benefit from its use, supports a more selective application of sentinel
      lymph node biopsy to this group of patients.

PMID- 22399280
TI  - Patterns and predictive factors of lateral lymph node metastasis in papillary
      thyroid microcarcinoma.
AB  - OBJECTIVE: To determine the incidence and patterns of and to evaluate the
      predictive factors for lateral cervical lymph node metastasis (LNM) in papillary
      thyroid microcarcinoma (PTMC). STUDY DESIGN: Case series with chart review.
      SETTING: Academic university hospital. SUBJECTS AND METHODS: From March 2007 to
      September 2010, a retrospective review was performed of 490 patients with PTMC
      who underwent total thyroidectomy and central lymph node dissection with or
      without lateral cervical lymph node dissection. The clinicopathologic results
      were reviewed, and the incidence and patterns of lateral cervical lymph node
      metastasis were analyzed. RESULTS: The overall frequency of central and lateral
      LNM was 39.6% and 3.0%, respectively. The incidence of lateral lymph node
      metastasis in level IIa, III, IV, Vb, IIb, and Va was 46.7%, 53.3%, 73.3%, 6.7%,
      6.7%, and 20.0%, respectively. Lateral LNM without central LNM was observed in 3
      (0.6%) cases of PTMC. A multivariate analysis revealed that the predictive
      factors for the presence of lateral lymph node metastasis are male sex, increased
      tumor size, T4 stage, and pathologic central lymph node metastasis. CONCLUSION:
      Although lateral LNM was rare, the surgeon should perform thorough preoperative
      studies to look for lateral LNM in cases of PTMC if the patient is male, has a
      relatively larger tumor size, and has aggressive mass and also to look for the
      possibility of skip metastasis. Lymph node metastasis involving the spinal
      accessory chain (IIb) was not that rare, and careful level IIb lymph node
      dissection should be considered for patients who will undergo a modified radical
      neck dissection for lateral LNM.

PMID- 22399281
TI  - Risk factors for recurrent laryngeal nerve neuropraxia postthyroidectomy.
AB  - OBJECTIVE: Despite preservation of the recurrent laryngeal nerve (RLN), transient
      vocal cord paralysis (VCP) occurs after 1.2% to 10.9% of thyroidectomies. The
      objective of this study was to study risk factors for transient VCP after
      thyroidectomy. STUDY DESIGN: Prospective cohort study. SETTING: Academic teaching
      hospital. SUBJECTS AND METHODS: Two hundred fifteen consecutive thyroid surgeries
      performed by a single surgeon. All patients underwent preoperative and
      postoperative laryngoscopy. Patients with preexisting VCP or without
      postoperative laryngoscopy were excluded. Clinical and operative data were
      recorded prospectively at the time of thyroid surgery. The association between
      possible risk factors and occurrence of postoperative transient VCP was studied.
      RESULTS: Six patients were excluded (2 with preexisting VCP and 4 without
      postoperative laryngoscopy). There was 1 intentional sacrifice of an RLN and 1
      unintentional RLN transection. Of the remaining 322 RLNs at risk, 15 (4.7%) had
      postoperative VCP. Operative findings of cancer invading the RLN requiring sharp
      dissection to separate the nerve (P = .006) and operative findings of RLN
      extensively draped along the thyroid or intimately associated with the thyroid
      parenchyma at Berry's ligament (P = .03) were significantly associated with VCP.
      Revision surgery (P = .06) trended toward significance. Malignancy, central
      compartment neck dissection, extralaryngeal RLN branching, hyperthyroidism, and
      retrosternal extension were not significant. Of cases with follow-up
      laryngoscopic documentation of vocal function, 85% (11/13) showed full resolution
      of VCP, with 1 further case showing partial recovery. CONCLUSION: Invasive cancer
      and variants in the anatomic course of the RLN are risk factors for transient VCP
      after thyroidectomy.

PMID- 22399282
TI  - Laryngeal nerve monitoring: current utilization among head and neck surgeons.
AB  - OBJECTIVE: There is continued debate over the value of laryngeal nerve monitoring
      (LNM) during thyroidectomy. Previous studies have suggested that utilization of
      electromyographic endotracheal tubes for neuromonitoring is limited. We queried
      head and neck surgeons regarding their attitudes toward LNM. STUDY DESIGN:
      Voluntary survey. SETTING: Internet based. SUBJECTS AND METHODS: An anonymous
      survey of the members of the American Head and Neck Society was performed.
      Information was collected on participants' training history, practice setting,
      years of experience, and annual volume of thyroid and parathyroid surgeries.
      Participants' use of LNM and their beliefs regarding possible benefits were
      assessed. RESULTS: One hundred seventy surveys were completed (18% response
      rate). Of respondents, 65% use LNM in at least some thyroid and parathyroid
      cases, 37% always and 28% sometimes. The most commonly cited reasons for LNM use
      were "medical-legal protection" and "increased confidence." Comparing
      otolaryngologists to general surgeons, 43% versus 17% (P = .016) always use LNM,
      27% versus 36% sometimes use monitoring, and 30% versus 47% never use monitoring.
      Younger surgeons were more likely to use LNM. CONCLUSION: Currently, no consensus
      exists regarding the use of LNM during thyroid and parathyroid surgery. Our
      results suggest that LNM use has become more widespread. Irrespective of the
      reasons surgeons are adopting LNM, if this trend continues, LNM may eventually
      become routine practice among head and neck surgeons.

PMID- 22399284
TI  - Diffusion tensor imaging in moderate-to-severe pediatric traumatic brain injury:
      changes within an 18 month post-injury interval.
AB  - Traumatic brain injury (TBI) is a leading cause of death and disability in
      children, yet little is known regarding the pattern of TBI-related
      microstructural change and its impact on subsequent development. Diffusion tensor
      imaging (DTI) was used to examine between-group differences at two time points
      (planned intervals of 3 months and 18 months post-injury) and within-group
      longitudinal change in a group of children and adolescents aged 7-17 years with
      moderate-to-severe TBI (n = 20) and a comparison group of children with
      orthopedic injury (OI) (n = 21). In the 3- and 18-month cross-sectional analyses,
      tract-based spatial statistics (TBSS) generally revealed decreased fractional
      anisotropy (FA) and increased apparent diffusion coefficient (ADC) in the TBI
      group in regions of frontal, temporal, parietal, and occipital white matter as
      well as several deep subcortical structures, though areas of FA decrease were
      more prominent at the 3-month assessment, and areas of ADC increase were more
      prominent at the 18 month assessment, particularly in the frontal regions. In
      terms of the within-group changes over time, the OI group demonstrated primarily
      diffuse increases in FA over time, consistent with previous findings of DTI
      measured white matter developmental change. The TBI group demonstrated primarily
      regions of FA decrease and ADC increase over time, consistent with presumed
      continued degenerative change, though regions of ADC decrease were also
      appreciated. These results suggest that TBI-related microstructural changes are
      dynamic in children and continue until at least 18 months post-injury.
      Understanding the course of these changes in DTI metrics may be important in TBI
      for facilitating advances in management and intervention.

PMID- 22399283
TI  - Modulation of inflammatory and profibrotic signaling in a rabbit model of acute
      phonotrauma using triamcinolone.
AB  - OBJECTIVE: To investigate the hypothesis that prophylactic triamcinolone
      modulates acute vocal fold inflammatory and profibrotic signaling during acute
      phonotrauma. STUDY DESIGN: In vivo rabbit phonation model. SETTING: Academic
      medical center. SUBJECTS AND METHODS: Forty New Zealand white breeder rabbits
      were randomly assigned to 1 of 4 groups: control (no intervention), no treatment
      (30 minutes of raised intensity phonation), sham treatment (bilateral
      intralaryngeal triamcinolone acetonide injection at 0 ug/25 uL followed by 30
      minutes of raised intensity phonation), or steroid treatment (bilateral
      intralaryngeal triamcinolone acetonide injection at 400 ug/25 uL followed by 30
      minutes of raised intensity phonation). Quantitative polymerase chain reaction
      (qPCR) was used to investigate gene expression levels of cyclooxygenase-2 (COX
      2), interleukin (IL)-1beta, and transforming growth factor (TGF)-beta1. RESULTS:
      Results revealed a significant main effect for COX-2 (P = .002). Post hoc testing
      revealed that rabbits receiving no treatment (15.10) had higher COX-2 gene
      expression than control (5.90; P < .001). There were no significant differences
      in COX-2 expression between treatment groups. Results revealed a significant main
      effect for IL-1beta (P < .001). Post hoc testing revealed that rabbits receiving
      no treatment (14.70) had higher IL-1beta gene expression than control (6.30) (P =
      .001). There were no significant differences in IL-1beta gene expression between
      treatment groups. There were no significant differences in TGF-beta1 gene
      expression (P = .525) between treatment and control groups. CONCLUSION: Given
      conflicting evidence, further studies are necessary to investigate vocal fold
      steroid injections prior to and following the induction of phonotrauma.
      Prophylactic administration of triamcinolone immediately prior to acute
      phonotrauma resulted in no significant changes in COX-2, IL-1beta, and TGF-beta1
      gene transcript levels.

PMID- 22399285
TI  - Dry powder inhalers: study of the parameters influencing adhesion and dispersion
      of fluticasone propionate.
AB  - Interactions between particles are dependent on the physicochemical
      characteristics of the interacting particles but it is also important to consider
      the manufacturing process. Blending active pharmaceutical ingredient (API) with
      carrier is a critical stage that determines the blend homogeneity and is the
      first step towards obtaining the final quality of the powder blend. The aim of
      this work was to study parameters that influence the interactions between API and
      carrier in adhesive mixtures used in DPI and their effect on API dispersion. The
      study was done with fluticasone propionate blended with lactose 'Lactohale 200'.
      The study was based on the influence of the operating conditions (speed, mixing
      time, resting steps during mixing), the size of the carrier and the storage
      conditions on the blend properties and on the API dispersion. The quality of the
      blends was examined by analysing the API content uniformity. Adhesion
      characteristics were evaluated by submitting mixtures to a sieving action by air
      depression with the Alpine air-jet sieve. Aerodynamic evaluation of fine particle
      fraction (FPF) was obtained using a Twin Stage Impinger; the FPF being defined as
      the mass percentage of API below 6.4 MUm. For good dispersion and therefore good
      homogeneity of the API in the carrier particles, speed and powder blending time
      have to be sufficient, but not too long to prevent the appearance of static
      electricity, which is not favourable to homogeneity and stability. The FPF
      increases with the decrease in the carrier size. The storage conditions have also
      to be taken into consideration. Higher humidity favours the adhesion of API on
      the carrier and decreases the FPF.

PMID- 22399286
TI  - Chemometrics analysis for investigation of retention behavior of hazardous
      compounds in effluents.
AB  - The toxic substances, pesticides, and organic contaminants in effluents can
      potentially be causing damage that includes increased cancer risk; liver, kidney,
      stomach, nervous system, and immune system problems; reproductive difficulties;
      cataracts; and anemia. A quantitative structure-retention relationship (QSRR) was
      developed using the partial least square (PLS), kernel PLS (KPLS), and Levenberg
      Marquardt artificial neural network (L-M ANN) approach for chemometrics study.
      The data which contained retention time (RT) of the 47 hazardous compounds in
      effluents were obtained by reverse-phase high-performance liquid chromatography.
      Genetic algorithm was employed as a factor selection procedure for PLS and KPLS
      modeling methods. By comparing the results, GA-PLS descriptors are selected for L
      M ANN. Finally, a model with a low prediction error and a good correlation
      coefficient was obtained by L-M ANN. The described model does not require
      experimental parameters and potentially provides useful prediction for RT of new
      compounds. This is the first research on the QSRR of hazardous compounds in
      effluents using the chemometrics models.

PMID- 22399287
TI  - Membrane topology and intracellular processing of cyclin M2 (CNNM2).
AB  - Recently, mutations in the cyclin M2 (CNNM2) gene were identified to be causative
      for severe hypomagnesemia. In kidney, CNNM2 is a basolaterally expressed protein
      with predominant expression in the distal convoluted tubule. Transcellular
      magnesium (Mg(2+)) reabsorption in the distal convoluted tubule represents the
      final step before Mg(2+) is excreted into the urine, thus fine-tuning its final
      excretion via a tightly regulated mechanism. The present study aims to get
      insight in the structure of CNNM2 and to characterize its post-translational
      modifications. Here, membrane topology studies using intramolecular epitopes and
      immunocytochemistry showed that CNNM2 has an extracellular N terminus and an
      intracellular C terminus. This suggests that one of the predicted transmembrane
      regions might be re-entrant. By homology modeling, we demonstrated that the loss
      of-function mutation as found in patients disturbs the potential ATP binding by
      the intracellular cystathionine beta-synthase domains. In addition, the cellular
      processing pathway of CNNM2 was exposed in detail. In the endoplasmic reticulum,
      the signal peptidase complex cleaves off a large N-terminal signal peptide of
      about 64 amino acids. Mutagenesis screening showed that CNNM2 is glycosylated at
      residue Asn-112, stabilizing CNNM2 on the plasma membrane. Interestingly, co
      immunoprecipitation studies evidenced that CNNM2a forms heterodimers with the
      smaller isoform CNNM2b. These new findings on CNNM2 structure and processing may
      aid to elucidate the physiological role of CNNM2 in Mg(2+) reabsorption in the
      kidney.

PMID- 22399288
TI  - Distinct acyl protein transferases and thioesterases control surface expression
      of calcium-activated potassium channels.
AB  - Protein palmitoylation is rapidly emerging as an important determinant in the
      regulation of ion channels, including large conductance calcium-activated
      potassium (BK) channels. However, the enzymes that control channel palmitoylation
      are largely unknown. Indeed, although palmitoylation is the only reversible lipid
      modification of proteins, acyl thioesterases that control ion channel
      depalmitoylation have not been identified. Here, we demonstrate that
      palmitoylation of the intracellular S0-S1 loop of BK channels is controlled by
      two of the 23 mammalian palmitoyl-transferases, zDHHC22 and zDHHC23.
      Palmitoylation by these acyl transferases is essential for efficient cell surface
      expression of BK channels. In contrast, depalmitoylation is controlled by the
      cytosolic thioesterase APT1 (LYPLA1), but not APT2 (LYPLA2). In addition, we
      identify a splice variant of LYPLAL1, a homolog with ~30% identity to APT1, that
      also controls BK channel depalmitoylation. Thus, both palmitoyl acyltransferases
      and acyl thioesterases display discrete substrate specificity for BK channels.
      Because depalmitoylated BK channels are retarded in the trans-Golgi network,
      reversible protein palmitoylation provides a critical checkpoint to regulate exit
      from the trans-Golgi network and thus control BK channel cell surface expression.

PMID- 22399290
TI  - S100 proteins modulate protein phosphatase 5 function: a link between CA2+ signal
      transduction and protein dephosphorylation.
AB  - PP5 is a unique member of serine/threonine phosphatases comprising a regulatory
      tetratricopeptide repeat (TPR) domain and functions in signaling pathways that
      control many cellular responses. We reported previously that Ca(2+)/S100 proteins
      directly associate with several TPR-containing proteins and lead to dissociate
      the interactions of TPR proteins with their client proteins. Here, we identified
      protein phosphatase 5 (PP5) as a novel target of S100 proteins. In vitro binding
      studies demonstrated that S100A1, S100A2, S100A6, and S100B proteins specifically
      interact with PP5-TPR and inhibited the PP5-Hsp90 interaction. In addition, the
      S100 proteins activate PP5 by using a synthetic phosphopeptide and a
      physiological protein substrate, Tau. Overexpression of S100A1 in COS-7 cells
      induced dephosphorylation of Tau. However, S100A1 and permanently active S100P
      inhibited the apoptosis signal-regulating kinase 1 (ASK1) and PP5 interaction,
      resulting the inhibition of dephosphorylation of phospho-ASK1 by PP5. The
      association of the S100 proteins with PP5 provides a Ca(2+)-dependent regulatory
      mechanism for the phosphorylation status of intracellular proteins through the
      regulation of PP5 enzymatic activity or PP5-client protein interaction.

PMID- 22399289
TI  - Disabled-2 protein facilitates assembly polypeptide-2-independent recruitment of
      cystic fibrosis transmembrane conductance regulator to endocytic vesicles in
      polarized human airway epithelial cells.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated
      Cl(-) channel expressed in the apical plasma membrane of fluid-transporting
      epithelia, where the plasma membrane abundance of CFTR is in part controlled by
      clathrin-mediated endocytosis. The protein networks that control CFTR endocytosis
      in epithelial cells have only been partially explored. The assembly polypeptide-2
      complex (AP-2) is the prototypical endocytic adaptor critical for optimal
      clathrin coat formation. AP-2 is essential for recruitment of cargo proteins
      bearing the YXXPhi motif. Although AP-2 interacts directly with CFTR in vitro and
      facilitates CFTR endocytosis in some cell types, it remains unknown whether it is
      critical for CFTR uptake into clathrin-coated vesicles (CCVs). Disabled-2 (Dab2)
      is a clathrin-associated sorting protein (CLASP) that contributes to clathrin
      recruitment, vesicle formation, and cargo selection. In intestinal epithelial
      cells Dab2 was not found to play a direct role in CFTR endocytosis. By contrast,
      AP-2 and Dab2 were shown to facilitate CFTR endocytosis in human airway
      epithelial cells, although the specific mechanism remains unknown. Our data
      demonstrate that Dab2 mediates AP-2 independent recruitment of CFTR to CCVs in
      polarized human airway epithelial cells. As a result, it facilitates CFTR
      endocytosis and reduces CFTR abundance and stability in the plasma membrane.
      These effects are mediated by the DAB homology domain. Moreover, we show that in
      human airway epithelial cells AP-2 is not essential for CFTR recruitment to CCVs.

PMID- 22399291
TI  - Highly conserved salt bridge stabilizes rigid signal patch at extracellular loop
      critical for surface expression of acid-sensing ion channels.
AB  - Acid-sensing ion channels (ASICs) are non-selective cation channels activated by
      extracellular acidosis associated with many physiological and pathological
      conditions. A detailed understanding of the mechanisms that govern cell surface
      expression of ASICs, therefore, is critical for better understanding of the cell
      signaling under acidosis conditions. In this study, we examined the role of a
      highly conserved salt bridge residing at the extracellular loop of rat ASIC3
      (Asp(107)-Arg(153)) and human ASIC1a (Asp(107)-Arg(160)) channels. Comprehensive
      mutagenesis and electrophysiological recordings revealed that the salt bridge is
      essential for functional expression of ASICs in a pH sensing-independent manner.
      Surface biotinylation and immunolabeling of an extracellular epitope indicated
      that mutations, including even minor alterations, at the salt bridge impaired
      cell surface expression of ASICs. Molecular dynamics simulations, normal mode
      analysis, and further mutagenesis studies suggested a high stability and
      structural constrain of the salt bridge, which serves to separate an adjacent
      structurally rigid signal patch, important for surface expression, from a
      flexible gating domain. Thus, we provide the first evidence of structural
      requirement that involves a stabilizing salt bridge and an exposed rigid signal
      patch at the destined extracellular loop for normal surface expression of ASICs.
      These findings will allow evaluation of new strategies aimed at preventing
      excessive excitability and neuronal injury associated with tissue acidosis and
      ASIC activation.

PMID- 22399292
TI  - A helical conotoxin from Conus imperialis has a novel cysteine framework and
      defines a new superfamily.
AB  - Cone snail venoms are a rich source of peptides, many of which are potent and
      selective modulators of ion channels and receptors. Here we report the isolation
      and characterization of two novel conotoxins from the venom of Conus imperialis.
      These two toxins contain a novel cysteine framework, C-C-C-CC-C, which has not
      been found in other conotoxins described to date. We name it framework XXIII and
      designate the two toxins im23a and im23b; cDNAs of these toxins exhibit a novel
      signal peptide sequence, which defines a new K-superfamily. The disulfide
      connectivity of im23a has been mapped by chemical mapping of partially reduced
      intermediates and by NMR structure calculations, both of which establish a I-II,
      III-IV, V-VI pattern of disulfide bridges. This pattern was also confirmed by
      synthesis of im23a with orthogonal protection of individual cysteine residues.
      The solution structure of im23a reveals that im23a adopts a novel helical hairpin
      fold. A cluster of acidic residues on the surface of the molecule is able to bind
      calcium. The biological activity of the native and recombinant peptides was
      tested by injection into mice intracranially and intravenously to assess the
      effects on the central and peripheral nervous systems, respectively. Intracranial
      injection of im23a or im23b into mice induced excitatory symptoms; however, the
      biological target of these new toxins has yet to be identified.

PMID- 22399293
TI  - Escherichia coli TatA and TatB proteins have N-out, C-in topology in intact
      cells.
AB  - The twin arginine protein transport (Tat) system translocates folded proteins
      across the cytoplasmic membrane of prokaryotes and the thylakoid membrane of
      chloroplasts. In Escherichia coli, TatA, TatB, and TatC are essential components
      of the machinery. A complex of TatB and TatC acts as the substrate receptor,
      whereas TatA is proposed to form the Tat transport channel. TatA and TatB are
      related proteins that comprise an N-terminal transmembrane helix and an adjacent
      amphipathic helix. Previous studies addressing the topological organization of
      TatA have given conflicting results. In this study, we have addressed the
      topological arrangement of TatA and TatB in intact cells by labeling of
      engineered cysteine residues with the membrane-impermeable thiol reagent
      methoxypolyethylene glycol maleimide. Our results show that TatA and TatB share
      an N-out, C-in topology, with no evidence that the amphipathic helices of either
      protein are exposed at the periplasmic side of the membrane. We further show that
      the N-out, C-in topology of TatA is fixed and is not affected by the absence of
      other Tat components or by the overproduction of a Tat substrate. These data
      indicate that topological reorganization of TatA is unlikely to accompany Tat
      dependent protein transport.

PMID- 22399294
TI  - MicroRNA-214 suppresses growth and invasiveness of cervical cancer cells by
      targeting UDP-N-acetyl-alpha-D-galactosamine:polypeptide N
      acetylgalactosaminyltransferase 7.
AB  - MicroRNAs are a class of small noncoding RNAs that function as key regulators of
      gene expression at the post-transcriptional level. In this study, we demonstrate
      that miR-214 is frequently down-regulated in cervical cancer, and its expression
      reduces the proliferation, migration, and invasiveness of cervical cancer cells,
      whereas inhibiting its expression results in enhanced proliferation, migration,
      and invasion. miR-214 binds to the 3'-UTR of UDP-N-acetyl-alpha-D
      galactosamine:polypeptide N-acetylgalactosaminyltransferase 7 (GALNT7), thereby
      repressing GALNT7 expression. Furthermore, we are the first to show, using
      quantitative real-time PCR, that GALNT7 is frequently up-regulated in cervical
      cancer. The knockdown of GALNT7 markedly inhibits cervical cancer cell
      proliferation, migration, and invasion, whereas ectopic expression of GALNT7
      significantly enhances these properties, indicating that GALNT7 might function as
      an oncogene in cervical cancer. The restoration of GALNT7 expression can
      counteract the effect of miR-214 on cell proliferation, migration, and
      invasiveness of cervical cancer cells. Together, these results indicate that miR
      214 is a new regulator of GALNT7, and both miR-214 and GALNT7 play important
      roles in the pathogenesis of cervical cancer.

PMID- 22399296
TI  - p38gamma mitogen-activated protein kinase (MAPK) confers breast cancer hormone
      sensitivity by switching estrogen receptor (ER) signaling from classical to
      nonclassical pathway via stimulating ER phosphorylation and c-Jun transcription.
AB  - Estrogen receptor (ER) alpha promotes breast cancer growth by regulating gene
      expression through classical estrogen response element (ERE) binding and
      nonclassical (interaction with c-Jun at AP-1 sites) pathways. ER is the target
      for anti-estrogens such as tamoxifen (TAM). However, the potential for classical
      versus nonclassical ER signaling to influence hormone sensitivity is not known.
      Moreover, anti-estrogens frequently activate several signaling cascades besides
      the target ER, and the implications of these "off-target" signaling events have
      not been explored. Here, we report that p38gamma MAPK is selectively activated by
      treatment with TAM. This results in both phosphorylation of ER at Ser-118 and
      stimulation of c-Jun transcription, thus switching ER signaling from the
      classical to the nonclassical pathway leading to increased hormone sensitivity.
      Unexpectedly, phosphorylation at Ser-118 is required for ER to bind both p38gamma
      and c-Jun, thereby promoting ER relocation from ERE to AP-1 promoter sites. Thus,
      ER/Ser-118 phosphorylation serves as a central mechanism by which p38gamma
      regulates signaling transduction of ER with its inhibitor TAM.

PMID- 22399295
TI  - Galactose recognition by the apicomplexan parasite Toxoplasma gondii.
AB  - Toxosplasma gondii is the model parasite of the phylum Apicomplexa, which
      contains numerous obligate intracellular parasites of medical and veterinary
      importance, including Eimeria, Sarcocystis, Cryptosporidium, Cyclospora, and
      Plasmodium species. Members of this phylum actively enter host cells by a
      multistep process with the help of microneme protein (MIC) complexes that play
      important roles in motility, host cell attachment, moving junction formation, and
      invasion. T. gondii (Tg)MIC1-4-6 complex is the most extensively investigated
      microneme complex, which contributes to host cell recognition and attachment via
      the action of TgMIC1, a sialic acid-binding adhesin. Here, we report the
      structure of TgMIC4 and reveal its carbohydrate-binding specificity to a variety
      of galactose-containing carbohydrate ligands. The lectin is composed of six apple
      domains in which the fifth domain displays a potent galactose-binding activity,
      and which is cleaved from the complex during parasite invasion. We propose that
      galactose recognition by TgMIC4 may compromise host protection from galectin
      mediated activation of the host immune system.

PMID- 22399297
TI  - Proinflammatory actions of visfatin/nicotinamide phosphoribosyltransferase
      (Nampt) involve regulation of insulin signaling pathway and Nampt enzymatic
      activity.
AB  - Visfatin (also termed pre-B-cell colony-enhancing factor (PBEF) or nicotinamide
      phosphoribosyltransferase (Nampt)) is a pleiotropic mediator acting on many
      inflammatory processes including osteoarthritis. Visfatin exhibits both an
      intracellular enzymatic activity (nicotinamide phosphoribosyltransferase, Nampt)
      leading to NAD synthesis and a cytokine function via the binding to its
      hypothetical receptor. We recently reported the role of visfatin in prostaglandin
      E(2) (PGE(2)) synthesis in chondrocytes. Here, our aim was to characterize the
      signaling pathways involved in this response in exploring both the insulin
      receptor (IR) signaling pathway and Nampt activity. IR was expressed in human and
      murine chondrocytes, and visfatin triggered Akt phosphorylation in murine
      chondrocytes. Blocking IR expression with siRNA or activity using the hydroxy-2
      naphthalenyl methyl phosphonic acid tris acetoxymethyl ester (HNMPA-(AM)(3))
      inhibitor diminished visfatin-induced PGE(2) release in chondrocytes. Moreover,
      visfatin-induced IGF-1R(-/-) chondrocytes released higher concentration of PGE(2)
      than IGF-1R(+/+) cells, a finding confirmed with an antibody that blocked IGF-1R.
      Using RT-PCR, we found that visfatin did not regulate IR expression and that an
      increased insulin release was also unlikely to be involved because insulin was
      unable to increase PGE(2) release. Inhibition of Nampt activity using the APO866
      inhibitor gradually decreased PGE(2) release, whereas the addition of exogenous
      nicotinamide increased it. We conclude that the proinflammatory actions of
      visfatin in chondrocytes involve regulation of IR signaling pathways, possibly
      through the control of Nampt enzymatic activity.

PMID- 22399298
TI  - Eukaryotic translation elongation factor 1A induces anoikis by triggering cell
      detachment.
AB  - Anoikis, apoptosis because of loss of cell anchorage, is crucial for tissue
      homeostasis. Fibronectin not only provides a scaffold for cell anchorage but also
      harbors a cryptic antiadhesive site capable of inducing beta1-integrin
      inactivation. In this study, this cryptic antiadhesive site is implicated in
      spontaneous induction of anoikis. Nontransformed fibroblasts (NIH3T3) adhering to
      a fibronectin substratum underwent anoikis during serum starvation culture. This
      anoikis was caused by proteolytic exposure of the cryptic antiadhesive site in
      fibronectin by matrix metalloproteinase. Eukaryotic elongation factor 1A (eEF1A)
      was identified as a membrane receptor for the exposed antiadhesive site. Serum
      starvation raised the membrane residence of eEF1A, and siRNA-based disruption of
      this increase rendered cells anoikis-resistant. By contrast, cells became more
      susceptible to anoikis in parallel with increased membrane residence of eEF1A by
      enforced expression. These results demonstrate that eEF1A acts as a membrane
      receptor for the cryptic antiadhesive site of fibronectin, which contributes to
      cell regulation, including anoikis, through negative regulation of cell
      anchorage.

PMID- 22399299
TI  - Intracellular modulation of signaling pathways by annexin A6 regulates terminal
      differentiation of chondrocytes.
AB  - Annexin A6 (AnxA6) is highly expressed in hypertrophic and terminally
      differentiated growth plate chondrocytes. Rib chondrocytes isolated from newborn
      AnxA6-/- mice showed delayed terminal differentiation as indicated by reduced
      terminal differentiation markers, including alkaline phosphatase, matrix
      metalloproteases-13, osteocalcin, and runx2, and reduced mineralization. Lack of
      AnxA6 in chondrocytes led to a decreased intracellular Ca(2+) concentration and
      protein kinase C alpha (PKCalpha) activity, ultimately resulting in reduced
      extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein
      kinase (MAPK) activities. The 45 C-terminal amino acids of AnxA6 (AnxA6(1-627))
      were responsible for the direct binding of AnxA6 to PKCalpha. Consequently,
      transfection of AnxA6-/- chondrocytes with full-length AnxA6 rescued the reduced
      expression of terminal differentiation markers, whereas transfection of AnxA6-/-
      chondrocytes with AnxA6(1-627) did not or only partially rescued the decreased
      mRNA levels of terminal differentiation markers. In addition, lack of AnxA6 in
      matrix vesicles, which initiate the mineralization process in growth plate
      cartilage, resulted in reduced alkaline phosphatase activity and Ca(2+) and
      inorganic phosphate (P(i)) content and the inability to form hydroxyapatite-like
      crystals in vitro. Histological analysis of femoral, tibial, and rib growth
      plates from newborn mice revealed that the hypertrophic zone of growth plates
      from newborn AnxA6-/- mice was reduced in size. In addition, reduced
      mineralization was evident in the hypertrophic zone of AnxA6-/- growth plate
      cartilage, although apoptosis was not altered compared with wild type growth
      plates. In conclusion, AnxA6 via its stimulatory actions on PKCalpha and its role
      in mediating Ca(2+) flux across membranes regulates terminal differentiation and
      mineralization events of chondrocytes.

PMID- 22399301
TI  - Trpc1 ion channel modulates phosphatidylinositol 3-kinase/Akt pathway during
      myoblast differentiation and muscle regeneration.
AB  - We previously showed in vitro that calcium entry through Trpc1 ion channels
      regulates myoblast migration and differentiation. In the present work, we used
      primary cell cultures and isolated muscles from Trpc1(-/-) and Trpc1(+/+) murine
      model to investigate the role of Trpc1 in myoblast differentiation and in muscle
      regeneration. In these models, we studied regeneration consecutive to cardiotoxin
      induced muscle injury and observed a significant hypotrophy and a delayed
      regeneration in Trpc1(-/-) muscles consisting in smaller fiber size and increased
      proportion of centrally nucleated fibers. This was accompanied by a decreased
      expression of myogenic factors such as MyoD, Myf5, and myogenin and of one of
      their targets, the developmental MHC (MHCd). Consequently, muscle tension was
      systematically lower in muscles from Trpc1(-/-) mice. Importantly, the
      PI3K/Akt/mTOR/p70S6K pathway, which plays a crucial role in muscle growth and
      regeneration, was down-regulated in regenerating Trpc1(-/-) muscles. Indeed,
      phosphorylation of both Akt and p70S6K proteins was decreased as well as the
      activation of PI3K, the main upstream regulator of the Akt. This effect was
      independent of insulin-like growth factor expression. Akt phosphorylation also
      was reduced in Trpc1(-/-) primary myoblasts and in control myoblasts
      differentiated in the absence of extracellular Ca(2+) or pretreated with EGTA-AM
      or wortmannin, suggesting that the entry of Ca(2+) through Trpc1 channels
      enhanced the activity of PI3K. Our results emphasize the involvement of Trpc1
      channels in skeletal muscle development in vitro and in vivo, and identify a
      Ca(2+)-dependent activation of the PI3K/Akt/mTOR/p70S6K pathway during myoblast
      differentiation and muscle regeneration.

PMID- 22399300
TI  - S100P dissociates myosin IIA filaments and focal adhesion sites to reduce cell
      adhesion and enhance cell migration.
AB  - S100 proteins promote cancer cell migration and metastasis. To investigate their
      roles in the process of migration we have constructed inducible systems for S100P
      in rat mammary and human HeLa cells that show a linear relationship between its
      intracellular levels and cell migration. S100P, like S100A4, differentially
      interacts with the isoforms of nonmuscle myosin II (NMIIA, K(d) = 0.5 MUM; IIB,
      K(d) = 8 MUM; IIC, K(d) = 1.0 MUM). Accordingly, S100P dissociates NMIIA and IIC
      filaments but not IIB in vitro. NMIIA knockdown increases migration in non
      induced cells and there is no further increase upon induction of S100P, whereas
      NMIIB knockdown reduces cell migration whether or not S100P is induced. NMIIC
      knockdown does not affect S100P-enhanced cell migration. Further study shows that
      NMIIA physically interacts with S100P in living cells. In the cytoplasm, S100P
      occurs in discrete nodules along NMIIA-containing filaments. Induction of S100P
      causes more peripheral distribution of NMIIA filaments. This change is paralleled
      by a significant drop in vinculin-containing, actin-terminating focal adhesion
      sites (FAS) per cell. The induction of S100P, consequently, causes significant
      reduction in cellular adhesion. Addition of a focal adhesion kinase (FAK)
      inhibitor reduces disassembly of FAS and thereby suppresses S100P-enhanced cell
      migration. In conclusion, this work has demonstrated a mechanism whereby the
      S100P-induced dissociation of NMIIA filaments leads to a weakening of FAS,
      reduced cell adhesion, and enhanced cell migration, the first major step in the
      metastatic cascade.

PMID- 22399302
TI  - Regulation of karyopherin alpha1 and nuclear import by mammalian target of
      rapamycin.
AB  - Under conditions of reduced mitogen or nutritional substrate levels, the
      serine/threonine kinase target of rapamycin can augment the nuclear content of
      distinct transcription factors and promote the induction of stress response
      genes. In its latent (i.e., unphosphorylated) form, the transcription factor
      STAT1 regulates a subset of genes involved in immune modulation and apoptosis.
      Based on previous work indicating a functional relationship between mammalian
      target of rapamycin (mTOR) and the nuclear content of latent STAT1, we
      investigated the mechanism by which mTOR controls STAT1 nuclear import. By
      fluorescence confocal microscopy, inactivation of mTOR with rapamycin promoted
      the nuclear translocation of unphosphorylated STAT1, but not that of a STAT1
      mutant incapable of binding its nuclear import adaptor karyopherin-alpha1
      (KPNA1). By immunoprecipitation, KPNA1 was physically associated with mTOR and
      STAT1 in a complex that translocated to the nucleus in response to rapamycin.
      Although mTOR is not a kinase for KPNA1, the mTOR-associated phosphatase protein
      phosphatase 2A catalytic interacted directly with KPNA1 and regulated nuclear
      import of the mTOR-KPNA1 complex. KPNA1, or its interaction with STAT1, was
      required for the nuclear import of latent STAT1, transcriptional induction of the
      STAT1 gene, and caspase-3 activation under conditions of reduced mTOR activity
      (i.e. rapamycin, glucose starvation, serum withdrawal). Therefore, at low mitogen
      or nutrient levels, mTOR and protein phosphatase 2A catalytically control the
      constitutive nuclear import of latent STAT1 by KPNA1, which are key modulators of
      STAT1 expression and apoptosis.

PMID- 22399303
TI  - Venous and arterial thrombosis associated with HIV infection.
AB  - The advent of highly active antiretroviral therapy (HAART) and the appropriate
      use of prophylactic strategies to prevent opportunistic infections have
      drastically decreased human immunodeficiency virus (HIV) infection-related
      mortality. However, there is growing evidence that metabolic abnormalities
      associated with HIV infection and with its treatment may lead to an increased
      risk of cardiovascular (CV) events. Several studies showed an increased risk of
      symptomatic and subclinical CV events in these patients. On the other hand, the
      association with venous thromboembolic events is less compelling. This increased
      risk is possibly explained by the coexistence in this population of different
      risk factors determined by the HIV infection per se, by the higher prevalence of
      traditional CV risk factors such as obesity, smoking, hypertension,
      hyperlipidemia, and glucose intolerance, as compared with the general population,
      and by the effects of HAART. Thus, systematic identification and aggressive
      treatment of traditional risk factors seem to be necessary to prevent the
      development of cardiovascular disease in this population.

PMID- 22399305
TI  - Interpretation and recommended testing for antiphospholipid antibodies.
AB  - The antiphospholipid syndrome (APS) is defined by the association of arterial
      and/or venous thrombosis and/or pregnancy complications with the presence of at
      least one of the main laboratory-detected antiphospholipid antibodies (aPL)
      (i.e., lupus anticoagulants [LA], IgG and/or IgM anticardiolipin antibodies
      [aCL], and IgG and/or IgM anti-beta2-glycoprotein I antibodies [abeta2GPI]).
      During the last decade efforts have been made to improve the harmonization and
      reproducibility of laboratory detection of aPL and guidelines have been
      published. The prognostic significance of aPL is being clarified through the fine
      elucidation of their antigenic targets and pathogenic mechanisms. Several
      clinical studies have consistently reported that LA is a stronger risk factor for
      both arterial and venous thrombosis compared with aCL and abeta2GPI. In
      particular, LA activity dependent on the first domain of beta2-glycoprotein I and
      triple aPL positivity are prognosticators of the thrombotic and obstetric risks.
      Hopefully, this increasing knowledge will help improve diagnostic and treatment
      strategies for APS.

PMID- 22399304
TI  - Heparin-induced thrombocytopenia: an update.
AB  - Heparin-induced thrombocytopenia (HIT) is an immune response to heparin that can
      progress to severe thrombosis, amputation, and in some cases death. The diagnosis
      and treatment of HIT is complex, but needs to be considered in the clinical
      management of patients exposed to heparin due to its serious outcomes. Early
      diagnosis based on a comprehensive interpretation of clinical and laboratory
      information improves clinical outcomes. This begins with careful monitoring for
      thrombocytopenia and thrombosis during and for at least 5 to 10 days after
      heparin treatment of any dose and duration. Appropriate use and knowledgeable
      interpretation of laboratory tests for HIT are important, as these vary in
      sensitivity and specificity, with each type providing unique information.
      Clinical management of patients with HIT is with a non-heparin anticoagulant such
      as a direct thrombin inhibitor or danaparoid followed by a vitamin K antagonist
      for long-term treatment. Important drug-specific limitations, dosing, and
      monitoring guidelines must be respected for patient safety. There continues to be
      new developments in the field of HIT: laboratory testing, clinical scoring
      systems, and available new anticoagulants. Research and clinical studies will
      continue to address the unresolved issues and unmet clinical needs associated
      with HIT. This review summarizes the clinical management of HIT.

PMID- 22399306
TI  - Viral hepatitis and thrombosis: a narrative review.
AB  - Venous thromboembolism (VTE) is a multicausal disease. Among minor risk factors,
      acute infections in general are associated with a transient increased risk of
      VTE. However, acute hepatitis is usually not reported as a potential risk factor
      for VTE. Recent studies suggest a possible role of viral hepatitis in the
      development of VTE and, in particular, of portal vein thrombosis. In this
      narrative review, we will discuss the possible pathogenetic roles of
      cytomegalovirus, Epstein-Barr virus, and hepatitis A, B, and C viruses in VTE
      occurrence, and clinical evidence supporting this hypothesis. The hemostatic
      state in chronic liver disease and the role of coagulation in liver fibrosis will
      also be discussed.

PMID- 22399307
TI  - What have we learned about antiphospholipid syndrome from patients and
      antiphospholipid carrier cohorts?
AB  - Venous or arterial thrombosis or pregnancy morbidity in the presence of
      circulating antiphospholipid antibodies (aPL) define the antiphospholipid
      syndrome (APS). In terms of accepted APS criteria, aPL are detected by one
      coagulation test (lupus anticoagulant; LAC) and two immunoassays (anticardiolipin
      antibodies and anti-beta2-glycoptrotein I antibodies). In patients with APS, a
      single positive test carries a much lower risk of thrombosis recurrence or new
      pregnancy loss than does multiple (or triple) positivity. The same holds true for
      aPL carriers, namely subjects with laboratory tests but without clinical criteria
      for APS. Thus, very different risk categories exist among patients with APS as
      well as in carriers of aPL. Triple positivity apparently identifies the
      pathogenic autoantibody (antidomain I-II of beta2-glycoptrotein I); it is in this
      category of patients that trials on new therapeutic strategies should focus.

PMID- 22399308
TI  - Infection and inflammation as risk factors for thrombosis and atherosclerosis.
AB  - Severe infection and inflammation almost invariably lead to hemostatic
      abnormalities, ranging from insignificant laboratory changes to gross activation
      of coagulation that may result in localized thrombotic complications or systemic
      intravascular fibrin deposition. Systemic inflammation results in activation of
      coagulation, due to tissue factor-mediated thrombin generation, downregulation of
      physiological anticoagulant mechanisms, and inhibition of fibrinolysis.
      Proinflammatory cytokines, immune cells, and the endothelium play a central role
      in the differential effects on the coagulation and fibrinolysis pathways. Vice
      versa, activation of the coagulation system may importantly affect inflammatory
      responses by direct and indirect mechanisms. Similar mechanisms appear to play a
      role in the development of atherosclerosis and related arterial thrombosis. Apart
      from the general coagulation response to inflammation associated with severe
      infection, specific infections may cause distinct features, such as hemorrhagic
      fever or thrombotic microangiopathy.

PMID- 22399309
TI  - Cardiovascular risk in rheumatic patients: the link between inflammation and
      atherothrombosis.
AB  - In addition to a high prevalence of the metabolic syndrome and a significant
      under-diagnosis of vascular risk factors (VRFs), the effect of chronic
      inflammation also represents the cornerstone of the raised cardiovascular (CV)
      risk in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing
      spondylitis. Moreover, the finding that among current anti-inflammatory
      treatments, the use of tumor necrosis factor (TNF)-alpha blockers is associated
      with optimal rheumatologic and CV outcomes further supports the impact of
      inflammation on the CV risk. However, up-to-date treatment guidelines suggest
      that TNF-alpha blockers should be used only after the failure of traditional
      disease-modifying antirheumatic drugs (DMARDs). Early predictors of the
      therapeutic efficacy of traditional DMARDs are needed to identify candidates for
      TNF-alpha blocker treatment. Furthermore, whether the CV risk should be taken
      into account while choosing antirheumatic treatments is an emerging issue to be
      addressed. Common educational programs for specialists and general practitioners
      and appropriate CV prevention programs, taking into consideration traditional
      VRFs as well as the inflammatory status, should be planned to prevent ischemic
      events and to achieve optimal inflammation control in rheumatic patients.

PMID- 22399310
TI  - Sweet's syndrome with panuveitis resembling Behcet's disease.
AB  - PURPOSE: Sweet's syndrome (SS) is a skin disorder clinically characterized by
      fever, neutrophilia, and painful edematous plaques that occasionally causes
      posterior uveitis. We present two cases of SS with panuveitis resembling Behcet's
      disease (BD). SUBJECTS: Two patients with panuveitis associated with SS.
      OBSERVATIONS: The patient in case 1 was a 57-year-old Japanese man who developed
      acute severe iritis with hypopyon in the left eye. Fluorescein angiography (FA)
      performed 1 month after treatment showed findings observed in posterior uveitis:
      dye leakage from the optic disc and a petaloid pattern of hyperfluorescence in
      the macular region. The patient in case 2 was a 64-year-old Japanese man who
      complained of blurred vision in his left eye. Faint flare and occasional cells
      were present in the left anterior chamber, 2+ cells in the anterior vitreous, and
      2+ vitreous opacification in the left eye. FA demonstrated dye leakage from the
      optic disc and peripheral capillary vessels in both eyes. Both patients were
      diagnosed as having SS on the basis of fever, neutrophilia, elevated C-reactive
      protein, and skin biopsy results of neutrophilic infiltration without vasculitis.
      CONCLUSIONS: Differentiation of SS from BD based on the ocular manifestations is
      difficult. Ophthalmologists should bear in mind that SS can exhibit panuveitis
      resembling BD.

PMID- 22399311
TI  - Quality of life following surgery of ascending aorta and aortic arch with
      selective antegrade cerebral perfusion.
AB  - OBJECTIVE: Surgery of the ascending aorta and aortic arch has been challenging
      since its inception as neurological complications may occur significantly
      affecting the quality of life (QOL). METHODS:  From January 1998 to December
      2007, 79 patients mainly suffering aortic dissection (65%) or true aortic
      aneurysm (34%) underwent surgery on the aortic arch employing deep hypothermic
      circulatory arrest and selective antegrade cerebral perfusion. QOL was assessed
      with the sickness-impact-profile (SIP) comprising 136 questions and 12
      categories. RESULTS: All patients underwent replacement of the ascending aorta,
      combined with a partial (hemiarch) (n = 33; 42%) or total (n = 46, 58%) arch
      replacement. Thirty-day mortality was 17.7% (n = 14 patients). Perioperatively,
      three patients (3.8%) suffered a transitory ischemic attack (TIA) and 5.1%
      patients suffered a stroke. The median score of the complete questionnaire was
      4.7, which demonstrates excellent QOL following such complex surgical procedures.
      The median physical dimension was 2.5 (0; 8), the psychosocial median score was
      3.7 (1.2; 16.1), both underline an only minimal impairment of the daily life.
      CONCLUSION:  The QOL after following the surgery of ascending aorta and aortic
      arch with selective antegrade cerebral perfusion is excellent on the long-term as
      assessed by the SIP.

PMID- 22399312
TI  - Polymorphisms of the pro-opiomelanocortin and agouti-related protein genes and
      their association with chicken production traits.
AB  - Pro-opiomelanocortin (POMC) and agouti-related protein (AGRP) are hypothalamic
      neuropeptides that play a central role in the regulation of food intake and
      energy expenditure and for this reason the variations in the POMC and AGRP genes
      in chicken were examined by screening the DNA pools. Two silent cSNPs mutations
      in POMC gene and one silent cSNP mutation in AGRP gene were identified. PCR
      restriction fragment length polymorphism (RFLP) was used to test the cSNPs c.
      C495T in the POMC and c. C9T in the AGRP gene in the F2 resource population of
      Gushi chicken crossed with Anak broiler. The association analysis on the
      polymorphisms of POMC, AGRP gene and production traits showed that the c. C495T
      mutation in the POMC gene was significantly linked to the pelvis breadth at 4
      weeks of age (P = 0.035), body weight at 2 weeks of age (P = 0.013) and was
      highly significantly linked to the chest depth at 12 weeks of age (P = 0.006).
      The c. T9T genotype in the AGRP gene was associated with a low breast muscle
      water loss rate (P = 0.025), increased chest width at 12 weeks of age (P = 0.005)
      and body weight at 2 weeks of age (P = 0.036), a high slaughter rate (P = 0.049)
      and semi-evisceration weight (P = 0.019). These findings may have important
      implications for the molecular aspects of chicken breeding.

PMID- 22399313
TI  - Partial rescue of Rett syndrome by omega-3 polyunsaturated fatty acids (PUFAs)
      oil.
AB  - Evidence of enhanced oxidative stress (O.S.) and lipid peroxidation has been
      reported in patients with Rett syndrome (RTT), a relatively rare
      neurodevelopmental disorder progressing in 4-stages, and mainly caused by loss-of
      function mutations in the methyl-CpG-binding protein 2. No effective therapy for
      preventing or arresting the neurologic regression in the disease in its various
      clinical presentations is available. Based on our prior evidence of enhanced O.S.
      and lipid peroxidation in RTT patients, herein we tested the possible therapeutic
      effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs), known
      antioxidants with multiple effects, on the clinical symptoms and O.S. biomarkers
      in the earliest stage of RTT. A total of 20 patients in stage I were randomized
      (n = 10 subjects per arm) to either oral supplementation with omega-3 PUFAs
      containing fish oil (DHA: 72.9 +/- 8.1 mg/kg b.w./day; EPA: 117.1 +/- 13.1 mg/kg
      b.w./day; total omega-3 PUFAs: 246.0 +/- 27.5 mg/kg b.w./day) for 6 months or no
      treatment. Primary outcomes were potential changes in clinical symptoms, with
      secondary outcomes including variations for five O.S. markers in plasma and/or
      erythrocytes (nonprotein bound iron, F(2)-dihomo-isoprostanes, F(3)-isoprostanes,
      F(4)-neuroprostanes, and F(2)-isoprostanes). A significant reduction in the
      clinical severity (in particular, motor-related signs, nonverbal communication
      deficits, and breathing abnormalities) together with a significant decrease in
      all the examined O.S. markers was observed in the omega-3 PUFAs supplemented
      patients, whereas no significant changes were evidenced in the untreated group.
      For the first time, these findings strongly suggest that a dietary intervention
      in this genetic disease at an early stage of its natural history can lead to a
      partial clinical and biochemical rescue.

PMID- 22399315
TI  - Fuzzy complexes: a more stochastic view of protein function.
AB  - Intrinsically disordered proteins (IDPs) are widespread in eukaryotic proteomes
      and challenge the classical structure-function paradigm that equates a folded 3-D
      structure with protein function. However, IDPs often function by molecular
      recognition, in which they bind a partner molecule and undergo "induced folding"
      or "disorder-to-order transition" upon binding, which apparently suggests that in
      a functional context IDPs become ordered. Whereas this observation would restore
      the "prestige" of the classical structure-function paradigm, a closer inspection
      of the complexes of IDPs reveals that they do not always become fully ordered,
      but preserve functionally significant disorder in the complex with their binding
      partner(s). This phenomenon, which we termed "fuzziness", is the ultimate
      extension of structural disorder to the functional native state of proteins. In
      this introductory chapter, we outline the most important aspects of fuzziness,
      such as its structural categories, molecular mechanisms of function it mediates
      and the biological processes, in which it plays a distinguished role. As
      confirmed by all the other chapters of the book, we will show that new cases of
      fuzziness pop up at an accelerating pace, underscoring that this phenomenon
      presents a widespread novel paradigm of protein structure and function.

PMID- 22399314
TI  - Influence of different CLA isomers on insulin resistance and adipocytokines in
      pre-diabetic, middle-aged men with PPARgamma2 Pro12Ala polymorphism.
AB  - Conjugated linoleic acids (CLAs) are natural PPARgamma ligands, which showed
      conflicting effects on metabolism in humans. We examined metabolic effects of
      different isomers of CLA in subjects with PPARgamma2 Pro12Ala polymorphisms. A
      total of 35 men underwent four intervention periods in a crossover study design:
      subjects with either genotypes received c9, t11 CLA or t10, c12 CLA, a
      commercially available 1:1 mix of both isomers or reference oil (linoleic acid
      (LA)). Adipocytokines, insulin, glucose and triglycerides were assessed in the
      fasting state and after a standardized mixed meal. Across all genotypes, there
      was a significant (p = 0.025) CLA treatment effect upon postprandial (pp) HOMA-IR
      values, with c9, t11 CLA and CLA isomer mix improving, but t10, c12 CLA isomer
      worsening. In Ala12Ala subjects, the t10, c12 isomer caused weight gain (p =
      0.03) and tended to increase postprandial insulin levels (p = 0.05). In Pro12Pro
      subjects, t10, c12 resulted in reduction in waist circumference (p = 0.03). The
      comparison of the different genotype groups revealed statistically different
      changes in fasting and postprandial insulin, HOMA-IR and leptin after
      intervention. c9, t11 CLA and the commercial CLA mix showed beneficial effects on
      insulin sensitivity compared with LA, while t10, c12 CLA adversely affects body
      weight and insulin sensitivity in different PPAR genotypes. CLA isomers have
      different effects on metabolism in Ala and Pro carriers.

PMID- 22399316
TI  - Dynamic fuzziness during linker histone action.
AB  - Linker histones are multi-domain nucleosome binding proteins that stabilize
      higher order chromatin structures and engage in specific protein-protein
      interactions. Here we emphasize the structural and functional properties of the
      linker histone C-terminal domain (CTD), focusing on its intrinsic disorder,
      interaction-induced secondary structure formation and dynamic fuzziness. We argue
      that the fuzziness inherent in the CTD is a primary molecular mechanism
      underlying linker histone function in the nucleus.

PMID- 22399317
TI  - Intrinsic protein flexibility in regulation of cell proliferation: advantages for
      signaling and opportunities for novel therapeutics.
AB  - It is now widely recognized that intrinsically disordered (or unstructured)
      proteins (IDPs, or IUPs) are found in organisms from all kingdoms of life. In
      eukaryotes, IDPs are highly abundant and perform a wide range of biological
      functions, including regulation and signaling. Despite increased interest in
      understanding the structural biology of IDPs, questions remain regarding the
      mechanisms through which disordered proteins perform their biological
      function(s). In other words, what are the relationships between disorder and
      function for IDPs? Several excellent reviews have recently been published that
      discuss the structural properties of IDPs.1-3 Here, we discuss two IDP systems
      which illustrate features of dynamic complexes. In the first section, we discuss
      two IDPs, p21 and p27, which regulate the mammalian cell division cycle by
      inhibiting cyclin-dependent kinases (Cdks). In the second section, we discuss
      recent results from Follis, Hammoudeh, Metallo and coworkers demonstrating that
      the IDP Myc can be bound and inhibited by small molecules through formation of
      dynamic complexes. Previous studies have shown that polypeptide segments of p21
      and p27 are partially folded in isolation and fold further upon binding their
      biological targets. Interestingly, some portions of p27 which bind to and inhibit
      Cdk2/cyclin A remain flexible in the bound complex. This residual flexibility
      allows otherwise buried tyrosine residues within p27 to be phosphorylated by
      nonreceptor tyrosine kinases (NRTKs). Tyrosine phosphorylation relieves kinase
      inhibition, triggering Cdk2-mediated phosphorylation of a threonine residue
      within the flexible C-terminus of p27. This, in turn, marks p27 for
      ubiquitination and proteasomal degradation, unleashing full Cdk2 activity which
      drives cell cycle progression. p27, thus, constitutes a conduit for transmission
      of proliferative signals via posttranslational modifications. Importantly,
      activation of the p27 signaling conduit by oncogenic NRTKs contributes to
      tumorigenesis in some human cancers, including chronic myelogenous leukemia
      (CML)9 and breast cancer.10 Another IDP with important roles in human cancer is
      the proto-oncoprotein, Myc. Myc is a DNA binding transcription factor which
      critically drives cell proliferation in many cell types and is often deregulated
      in cancer. Myc is intrinsically disordered in isolation and folds upon binding
      another IDP, Max and DNA. Follis, Hammoudeh, Metallo and coworkers identified
      small molecules which bind disordered regions of Myc and inhibit its
      heterodimerization with Max. Importantly, these small molecules- through
      formation of dynamic complexes with Myc-have been shown to inhibit Myc function
      in vitro and in cellular assays, opening the door to IDP-targeted therapeutics in
      the future. The p21/p27 and Myc systems illustrate, from different perspectives,
      the role of dynamics in IDP function. Dynamic fluctuations are critical for
      p21/p27 signaling while the dynamic free state of Myc may represent a
      therapeutically approachable anticancer target. Herein we review the current
      state of knowledge related to these two topics in IDP research.

PMID- 22399318
TI  - Interplay between protein order, disorder and oligomericity in receptor
      signaling.
AB  - Receptor-mediated signaling plays an important role in health and disease. Recent
      reports have revealed that many proteins that do not adopt globular structures
      under native conditions, thus termed intrinsically disordered, are involved in
      cell signaling. Intriguingly, physiologically relevant oligomerization of
      intrinsically disordered proteins (IDPs) has been recently observed and shown to
      exhibit unique biophysical characteristics, including the lack of significant
      changes in chemical shift and peak intensity upon binding. On the other hand,
      ligand-induced or - tuned receptor oligomerization is known to be a general
      feature of various cell surface receptors and to play a crucial role in signal
      transduction. In this work, I summarize several distinct features of protein
      disorder that are especially important as related to signal transduction. I also
      hypothesize that interactions of IDPs with their protein or lipid partners
      represent a general biphasic process with the electrostatic-driven "no disorder
      to-order" fast interaction which, depending on the interacting partner, may or
      may not be accompanied by the hydrophobic-driven slow formation of a secondary
      structure. Further, I suggest signaling-related functional connections between
      protein order, disorder and oligomericity and hypothesize that receptor
      oligomerization induced or tuned upon ligand binding outside the cell is
      translated across the membrane into protein oligomerization inside the cell, thus
      providing a general platform, the Signaling Chain HOmoOLigomerization (SCHOOL)
      platform, for receptor-mediated signaling. This structures our current
      multidisciplinary knowledge and views of the mechanisms governing the coupling of
      recognition to signal transduction and cell response. Importantly, this approach
      not only reveals previously unrecognized striking similarities in the basic
      mechanistic principles of function of numerous functionally diverse and unrelated
      surface membrane receptors, but also suggests the similarity between therapeutic
      targets, thus opening new horizons for both fundamental and clinically relevant
      studies.

PMID- 22399319
TI  - Consequences of fuzziness in the NFkappaB/IkappaBalpha interaction.
AB  - This chapter provides a short review of various biophysical experiments that have
      been applied to the inhibitor of kappa B, IkappaBalpha and its binding partner,
      nuclear factor kappa B, or NFkappaB. The picture that emerges from amide
      hydrogen/deuterium exchange, NMR and binding kinetics experiments is one in which
      parts of both proteins are "fuzzy" in the free-state and some parts remain
      "fuzzy" in the NFkappaB-IkappaBalpha complex. The NFkappaB family of
      transcription factors responds to inflammatory cytokines with rapid
      transcriptional activation, in which NFkappaB enters the nucleus and binds DNA.
      Just as rapidly as transcription is activated, it is subsequently repressed by
      newly synthesized IkappaBalpha?that also enters the nucleus and removes NFkappaB
      from the DNA. Because IkappaBalpha?is an ankyrin repeat protein, it's "fuzziness"
      can be controlled by mutagenesis to stabilized the folded state. Experimental
      comparison with such stabilized mutants helps provide evidence that much of the
      system control depends on the "fuzziness" of IkappaBalpha.

PMID- 22399320
TI  - Roles for intrinsic disorder and fuzziness in generating context-specific
      function in Ultrabithorax, a Hox transcription factor.
AB  - Surprisingly few transcription factors drive animal development relative to the
      number and diversity of final tissues and body structures. Therefore, most
      transcription factors must function in more than one tissue. In a famous example,
      members of the Hox transcription factor family are expressed in contiguous
      stripes along the anterior/posterior axis during animal development. Individual
      Hox transcription factors specify all tissues within their expression domain and
      thus must respond to cellular cues to instigate the correct tissue-specific gene
      regulatory cascade. We describe how, in the Drosophila Hox protein Ultrabithorax,
      intrinsically disordered regions implement, regulate and co-ordinate multiple
      functions, potentially enabling context-specific gene regulation. The large N
      terminal disordered domain encodes most of the transcription activation domain
      and directly impacts DNA binding affinity by the Ubx homeodomain. Similarly, the
      C-terminal disordered domain alters DNA binding affinity and specificity,
      interaction with a Hox binding protein and strongly influences both transcription
      activation and repression. Phosphorylation of the N-terminal disordered domain
      and alternative splicing of the C-terminal disordered domain could allow the cell
      to both regulate and co-ordinate DNA binding, protein interactions and
      transcription regulation. For regulatory mechanisms relying on disorder to
      continue to be available when Ubx is bound to other proteins or DNA, fuzziness
      would need to be preserved in these macromolecular complexes. The intrinsically
      disordered domains in Hox proteins are predicted to be on the very dynamic end of
      the disorder spectrum, potentially allowing disorder to persist when Ubx is bound
      to proteins or DNA to regulate the function of these "fuzzy" complexes. Because
      both intrinsically disordered regions within Ubx have multiple roles, each region
      may implement several different regulatory mechanisms identified in fuzzy
      complexes. These intrinsic disorder-based regulatory mechanisms are likely to be
      critical for allowing Ubx to sense tissue identity and respond by implementing a
      context-specific gene regulatory cascade.

PMID- 22399321
TI  - Molecular recognition by the EWS transcriptional activation domain.
AB  - Interactions between Intrinsically Disordered Protein Regions (IDRs) and their
      targets commonly exhibit localised contacts via target-induced disorder to order
      transitions. Other more complex IDR target interactions have been termed "fuzzy"
      because the IDR does not form a well-defined induced structure. In some
      remarkable cases of fuzziness IDR function is apparently sequence independent and
      conferred by amino acid composition. Such cases have been referred to as "random
      fuzziness" but the molecular features involved are poorly characterised. The
      transcriptional activation domain (EAD) of oncogenic Ewing's Sarcoma Fusion
      Proteins (EFPs) is an ~280 residue IDR with a biased composition restricted to
      Ala, Gly, Gln, Pro, Ser, Thr and Tyr. Multiple aromatic side chains (exclusively
      from Try residues) and the particular EAD composition are crucial for molecular
      recognition but there appears to be no other major geometrically constrained
      requirement. Computational analysis of the EAD using PONDR (Molecular Kinetics,
      Inc. http://www.pondr. com) complements the functional data and shows,
      accordingly, that propensity for structural order within the EAD is conferred by
      Tyr residues. To conclude, molecular recognition by the EAD is extraordinarily
      malleable and involves multiple aromatic contacts facilitated by a flexible
      peptide backbone and, most likely, a limited number of weaker contributions from
      amenable side chains. I propose to refer to this mode of fuzzy recognition as
      "polyaromatic", noting that it shares some fundamental features with the
      "polyelectrostatic" (phosphorylation-dependent) interaction of the Sic1 Cdk
      inhibitor and Cdc4._I will also speculate on more detailed models for molecular
      recognition by the EAD and their relationship to native (non-oncogenic) EAD
      function.

PMID- 22399322
TI  - The measles virus N(TAIL)-XD complex: an illustrative example of fuzziness.
AB  - In this chapter, I focus on the biochemical and structural characterization of
      the complex between the intrinsically disordered C-terminal domain of the measles
      virus nucleoprotein (N(TAIL)) and the C-terminal X domain (XD) of the viral
      phosphoprotein (P). I summarize the main experimental data available so far
      pointing out the prevalently disordered nature of N(TAIL) even after complex
      formation and the role of the flexible C-terminal appendage in the binding
      reaction. I finally discuss the possible functional role of these residual
      disordered regions within the complex in terms of their ability to capture other
      regulatory, binding partners.

PMID- 22399323
TI  - Fuzziness in the core of the human pathogenic viruses HCV and HIV.
AB  - Nucleocapsid proteins are the molecular jacks-of-all-trades of small RNA viruses
      because they play pivotal roles in viral genomic RNA selection and packaging,
      regulate genome replication and virus budding and at the same time orchestrate a
      complex, dynamic interaction network with host cell proteins contributing to
      viral persistence and pathogenecity. These promiscuous interactions are made
      possible by the intrinsic flexibility of viral nucleocapsid proteins,
      facilitating either simultaneous or sequential binding to a plethora of
      structurally unrelated substrates, resulting in flexible, ever-changing
      multiprotein, RNA-protein and lipid-protein complexes during the viral
      replicative cycle. In this chapter, we examine the flexibility and
      multifunctionality of the assemblages formed by the nucleocapsid proteins of two
      important human pathogens, hepatitis C virus and human immunodeficiency virus.

PMID- 22399324
TI  - Structural disorder and protein elasticity.
AB  - An emerging class of disordered proteins underlies the elasticity of many
      biological tissues. Elastomeric proteins are essential to the function of
      biological machinery as diverse as the human arterial wall, the capture spiral of
      spider webs and the jumping mechanism of fleas. In this chapter, we review what
      is known about the molecular basis and the functional role of structural disorder
      in protein elasticity. In general, the elastic recoil of proteins is due to a
      combination of internal energy and entropy. In rubber-like elastomeric proteins,
      the dominant driving force is the increased entropy of the relaxed state relative
      to the stretched state. Aggregates of these proteins are intrinsically disordered
      or fuzzy, with high polypeptide chain entropy. We focus our discussion on the
      sequence, structure and function of five rubber-like elastomeric proteins,
      elastin, resilin, spider silk, abductin and ColP. Although we group these
      disordered elastomers together into one class of proteins, they exhibit a broad
      range of sequence motifs, mechanical properties and biological functions.
      Understanding how sequence modulates both disorder and elasticity will help
      advance the rational design of elastic biomaterials such as artificial skin and
      vascular grafts.

PMID- 22399325
TI  - "Fuzziness" in the celular interactome: a historical perspective.
AB  - Some historical background is given for appreciating the impact of the empirical
      construct known as the cellular protein-protein interactome, which is a seemingly
      de novo entity that has arisen of late within the context of postgenomic systems
      biology. The approach here builds on a generalized principle of "fuzziness" in
      protein behavior, proposed by Tompa and Fuxreiter.(1) Recent controversies in the
      analysis and interpretation of the interactome studies are rationalized
      historically under the auspices of this concept. There is an extensive literature
      on protein-protein interactions, dating to the mid-1900s, which may help clarify
      the "fuzziness" in the interactome picture and, also, provide a basis for
      understanding the physiological importance of protein-protein interactions in
      vivo.

PMID- 22399326
TI  - Sociodemographic trends in bariatric surgery utilization in the USA.
AB  - Although bariatric surgery has become more accessible in recent years, it is
      unclear whether populations disproportionately affected by obesity are utilizing
      this treatment. A cross-sectional analysis of the Nationwide Inpatient Sample was
      performed. The sociodemographic characteristics (race, sex, age, insurance,
      median income), co-morbidities, and weight loss surgery type were analyzed.
      Bariatric surgeries increased six-fold from 17,678 in 1998 to 112,882 in 2004 (p
      < 0.001). Thereafter, bariatric surgeries declined to 93,733 in 2007 (p = 0.24).
      The proportion of individuals of Other race undergoing bariatric surgery
      significantly increased, while the proportion of Whites significantly decreased
      over time. The proportion of individuals in the lowest income quartile (<
      $25,000) increased, while those in the highest income percentile (> $45,000)
      decreased. From 1998 to 2007, the sociodemographic characteristics of the
      bariatric surgery population have changed, although those that are
      disproportionately affected by morbid obesity continue to be underrepresented.

PMID- 22399328
TI  - Differential item functioning for lesbians, bisexual, and heterosexual women in
      the center for epidemiological studies depression scale.
AB  - This study assessed whether the Center for Epidemiological Studies Depression
      Scale (CES-D) functions equivalently in assessing depressive symptom severity in
      lesbian, bisexual, and heterosexual women. Using differential item functioning
      methods, the authors examined (a) whether there is a bias in CES-D total scores
      and in individual item scores and (b) whether there are differences across female
      sexuality groups in the construct of depression assessed by the CES-D. Data were
      collected anonymously online from 273 women. The CES-D total score was unbiased
      across groups, but there were biases and construct differences in some individual
      symptoms. Thus, the findings suggest not only that researchers and clinicians can
      feel secure in using the CES-D in women of different sexual orientations but also
      that there may be interesting group differences in the manifestation of
      particular depressive symptoms.

PMID- 22399327
TI  - The use of telephone in genetic counseling versus in-person counseling: a
      randomized study on counselees' outcome.
AB  - Increased demand for genetic counseling services necessitates exploring
      alternatives to in-person counseling. Telephone counseling is a less time
      consuming and more cost-effective alternative. So far there is insufficient
      evidence to support a pre-counseling telephone model. This randomized
      questionnaire study aims to evaluate the oncogenetic counseling process and to
      compare the impact of the initial part of the oncogenetic counseling, when
      conducted via telephone versus in-person. The aspects of evaluations were:
      patients' expectations, satisfaction and experiences of genetic counseling, worry
      for developing hereditary cancer and health related quality of life. A total of
      215 participants representing several cancer syndromes were randomized to
      counseling via telephone or in-person. The questionnaires were completed before
      and after oncogenetic nurse counseling, and 1 year after the entire counseling
      process. Overall, a high satisfaction rate with the oncogenetic counseling
      process was found among the participants regardless of whether the oncogenetic
      nurse counseling was conducted by telephone or in-person. The results show that a
      considerable number of participants experienced difficulties with the process of
      creating a pedigree and dissatisfaction with information on surveillance and
      prevention. Affected participants reported lower levels in most SF-36 domains
      compared to non-affected and both groups reported lower levels as compared to a
      Swedish reference group. The results indicate that telephone pre-counseling works
      as well as in-person counseling. Emotional support during genetic counseling and
      information on recommended cancer prevention and surveillance should be improved.

PMID- 22399329
TI  - Damage mechanics of porcine flexor tendon: mechanical evaluation and modeling.
AB  - Porcine flexor tendons underwent cyclic and stress relaxation testing before and
      after strain exceeding elastic limit ("overstretch") to examine which mechanical
      parameters undergo changes following subfailure damage. From these data, we
      developed an "effective strain" damage model (in which the tendon is modeled as
      if being pulled to a lower strain). Damage was induced at three strain levels to
      determine the extent to which post-damage parameter changes were affected by
      overstretch strain level. We found that diffuse damage induced by overstretch
      decreased elastic and viscoelastic parameters obtained during testing. The stress
      response of tendon to strain is therefore altered following damage. We next
      compared the strain-dependent parameter behavior to damage-dependent behavior to
      determine the effective strain for each parameter. Effects of damage became more
      pronounced as strain during overstretch increased; following overstretch to 6.5,
      9, or 13% strain, effective strain was 2.43 +/- 0.33, 1.98 +/- 0.3, or 0.88 +/-
      0.43% strain, respectively. By determining the effective strain and using it to
      calculate predicted values of post-damage mechanical parameters, it was possible
      to predict the stress relaxation behavior of tendons with Schapery's nonlinear
      viscoelastic model. Using this approach, a single parameter predicts both elastic
      and viscoelastic compromise from known, strain-dependent behaviors.

PMID- 22399330
TI  - Distribution of internal strains around bony prominences in pigs.
AB  - Deep tissue injury (DTI) is a type of pressure ulcer in which tissue breakdown
      initiates at the bone-muscle interface under intact skin. Excessive deformation
      in the soft tissue, particularly around bony prominences, is believed to be one
      of the causes leading to the development of DTI. The main goal of this study was
      to measure the magnitude and distribution of strains within muscles surrounding
      the ischial tuberosities, induced by levels of external loading that encompass
      the range of loading experienced by the soft tissue in seated individuals. The
      experiments were conducted in adult pigs with intact spinal cords (n = 5) and
      pigs with partial spinal cord injury (SCI) (n = 2), one of which also had a DTI.
      A secondary goal was to obtain a preliminary assessment regarding the capacity of
      intermittent electrical stimulation (IES), an intervention for preventing the
      formation of DTI, to counteract the muscle compression caused by external
      loading. In intact animals, muscles subjected to external loads equivalent to 25%
      of body weight experienced maximal principal strains, minimal principal strains,
      and shear strains of 0.68, -0.3, and 0.4, respectively. These magnitudes
      increased by 91.9, 17.6, and 87.5%, respectively, when external loading increased
      to 50% body weight. Minimal to no further increases in strain magnitudes were
      seen with the 75% body weight loading level. In one animal with SCI and no DTI,
      strain magnitudes were on average 9.7% higher than those in the intact animals at
      the corresponding loading levels. The presence of a DTI in another animal with
      SCI reduced strain magnitudes by 28% compared to intact animals. The regions in
      the muscle that underwent the largest deformations were those between the ischial
      tuberosity and the external surface, and up to 2 cm ventral to the ischial
      tuberosity (furthest measured). Muscle contractions produced by IES increased the
      thickness of the tissue between the ischial tuberosities and skin during the
      period of stimulation by 10-20% for loading levels up to 75% of body weight in
      both intact and spinal cord injured pigs. This study provides the first
      measurements of strain around the ischial tuberosities in an animal model that
      resembles humans.

PMID- 22399331
TI  - A capillary fraction collector coupled to a fluorescence reader: a novel device
      to continuously quantify glutamate during microdialysis.
AB  - Microdialysis coupled to HPLC is the preferred method for quantification of
      glutamate (Glu) concentrations, both in normal and pathological conditions.
      However, HPLC is a time consuming technique that suffers from poor temporal
      resolution. Here we describe an alternative method to measure glutamate
      concentrations in small-volume dialysis samples by quantifying hydrogen peroxide
      released by glutamate oxidase using the Amplex Red method. This system permits
      continuous automatic sample collection and the detection of a fluorescent
      reaction product, resorufin, which provides a measure of the glutamate
      concentration. Quantification can be carried out in small microdialysis samples
      to allow a temporal resolution of 60 s. Both in vitro and in vivo tests showed
      that this method was reproducible and reliable, detecting Glu along a linear
      scale. To validate the proposed method, extracellular Glu concentrations in the
      rat brain were measured and correlated with electrophysiological activity prior,
      during and after seizure induction with 4-aminopyridine. This method may be
      adapted to monitor other biologically active compounds, including acetylcholine
      and glucose, as well as other compounds that generate hydrogen peroxide as a
      reaction product and may be used as an alternative to other neurochemical
      methods.

PMID- 22399333
TI  - Angiotensin III induces c-Jun N-terminal kinase leading to proliferation of rat
      astrocytes.
AB  - Previously, we showed in cultured rat astrocytes that angiotensin (Ang) III
      induced astrocyte proliferation and phosphorylation of ERK1/2 mitogen activated
      protein (MAP) kinases through interaction with the AT(1) receptor. In the current
      study, we determined whether the c-Jun N terminal kinase (JNK) MAP kinase pathway
      was similarly affected by the peptide in cultured brainstem astrocytes. Ang III
      induced JNK phosphorylation in a concentration- and time-dependent manner.
      Similar to ERK1/2 phosphorylation, maximal phosphorylation occurred with 100 nM
      Ang III and was apparent within a minute of exposure to the peptide. Peak effects
      were observed over a 5-15 min time range. Pretreatment of brainstem astrocytes
      with the JNK inhibitor, SP600125, prevented Ang III phosphorylation of JNK, as
      well as Ang III-mediated astrocyte growth. The selective AT(1) receptor
      antagonist, Losartan, prevented Ang III-induced JNK phosphorylation. Pretreatment
      of astrocytes with the AT(2) receptor blocker PD123319 was ineffective in
      preventing JNK phosphorylation by Ang III. Interestingly, both Ang II and Ang III
      induced JNK phosphorylation to a similar extent suggesting that the two peptides
      were equipotent in this effect. Our findings suggest that Ang III interacts with
      Ang AT(1) receptors to directly stimulate the JNK MAP kinase pathway leading to
      astrocyte growth. This study is the first to show that Ang III actions may
      involve the JNK MAP kinase pathway in astrocytes and provide key information that
      may lead to a better understanding of the functions of Ang III in the central
      nervous system, in particular in astrocytes.

PMID- 22399334
TI  - Myocardial fibroma diagnosed with MRI: importance of the late enhancement
      pattern.

PMID- 22399332
TI  - The interactions of nitric oxide and acetylcholine on penicillin-induced epilepsy
      in rats.
AB  - The aim of this study was to investigate the interaction between nitric oxide
      (NO) and acetylcholine (ACh) in penicillin-induced experimental epilepsy. Adult
      male Wistar rats weighing 220 +/- 35 g were used in the experiments. The
      epileptiform activity was induced by microinjection of penicillin (200 IU/1 MUl)
      into the left sensorymotor cortex. Electrocorticogram was recorded by using
      Ag/AgCl ball electrodes. Sodium nitroprusside (SNP), a NO donor, given
      intracortically 30 min after penicillin significantly reduced the spike frequency
      whereas ACh increased the epileptiform activity for 5 min. Atropine, an
      antagonist for muscarinic receptors, was given intracortically 30 min after
      penicillin and did not significantly affect epileptiform activity for 30 min. SNP
      given after atropine significantly suppressed the epileptiform activity. ACh
      given 10 min after Nomega-nitro-L: -arginine methyl ester (L-NAME), a nonspecific
      nitric oxide synthase inhibitor, did not have a significant effect on spike
      frequency. When ACh and SNP were administered together, penicillin induced
      epileptiform activity and spike frequency were significantly suppressed from the
      10th minute onwards. It can be concluded that ACh increases the penicillin
      induced epileptiform activity while co-administration of ACh and SNP produces a
      potent anticonvulsant effect as compared to SNP alone.

PMID- 22399335
TI  - The molecular basis of Notch signaling: a brief overview.
AB  - The Notch signaling pathway is evolutionarily conserved and has been associated
      with numerous developmental processes, including stem cell maintenance and adult
      tissue homeostasis. Notably, both abnormal increases and deficiencies of Notch
      signaling result in human developmental anomalies and cancer development implying
      that the precise regulation of the intensity and duration of Notch signals is
      imperative. Numerous studies have demonstrated that the aberrant gain or loss of
      Notch signaling pathway components is critically linked to multiple human
      diseases. In this chapter, we will briefly summarize the molecular basis of Notch
      signaling, focusing on the modulation of Notch signals, and its developmental
      outcomes including vessel formation and the onset of cancer.

PMID- 22399337
TI  - Metabolism and transportation pathways of GDP-fucose that are required for the O
      fucosylation of Notch.
AB  - Notch is a single-pass transmembrane receptor that mediates the local cell-cell
      interactions necessary for many cell-fate decisions. The extra cellular domain of
      Notch contains a tandem array of epidermal growth factor-like (EGF-like) repeats.
      Some of these EGF-like repeats are O-fucosylated by protein O-fucosyltransferase
      1 (O-fut1), which is essential for Notch signaling in Drosophila and mouse. This
      O-fucose is further modified by Fringe, a GlcNAc transferase and other
      glycosyltransferases (O-fut1 in Drosophila and Pofut1 in mouse), to form an O
      linked tetrasaccharide, which modulates Notch's selective binding to its ligands.

PMID- 22399338
TI  - Notch signaling and the generation of cell diversity in Drosophila neuroblast
      lineages.
AB  - Notch is a membrane bound transcription factor and it plays fundamental roles in
      many cell-cell interaction events usually involving directly neighboring cells
      relating an extrinsic signal of a sending cell to the nucleus of the receiving
      cell to modulate gene expression patterns in this cell. Notch regulates cell fate
      specification, cell proliferation as well as cell death in the contexts of many
      organs and cell types. Although the mechanisms of signal transduction from the
      cell surface to the nucleus are relatively simple, it is not fully understood how
      such a straightforward pathway can result in tremendously complex outcomes at the
      cellular level. This chapter discusses some of the known roles of Notch during
      central nervous system development in Drosophila. In the CNS, Notch is a major
      player in creating cellular diversity on the level of binary cell fates by
      possibly activating differential gene expression in sibling cells arising through
      asymmetric cell division. This chapter also raises some questions related to
      Notch function during neural cell fate specification which have not yet been
      satisfactorily addressed in the field. Finding answers to these questions may
      provide further insights into how cell-cell interactions in the nervous system
      involving Notch control the generation of cellular diversity.

PMID- 22399339
TI  - NEPRO: a novel Notch effector for maintenance of neural progenitor cells in the
      neocortex.
AB  - The Notch pathway is essential for maintaining neural progenitor cells (NPCs) in
      the developing brain. Activation of the pathway is sufficient to maintain NPCs,
      whereas loss-of-function mutations in the critical components of the pathway
      cause precocious neuronal differentiation and NPC depletion. Hairy and Enhancer
      of split (Hes)-type transcription factors have long been thought to be the only
      Notch effectors for the maintenance of NPCs. Recently, a novel nuclear protein,
      Nepro, has been identified as another critical effector of Notch. The Notch
      pathway is bifurcated into Nepro and Hes-type proteins in the early development
      of the neocortex. The combination of Nepro and Hes-type proteins is necessary and
      sufficient for maintaining NPCs downstream of Notch.

PMID- 22399340
TI  - Notch signaling and development of the hematopoietic system.
AB  - Notch signaling exerts multiple important functions in the hematopoietic system.
      Notch1-mediated signals are essential to induce the onset of definitive
      hematopoiesis within specialized domains of hemogenic endothelium in the fetal
      dorsal aorta. In contrast, Notch is dispensable for the subsequent maintenance of
      hematopoietic stem cells in the adult bone marrow. Notch is a key regulator of
      early T-cell development in the thymus. An expanding number of hematopoietic and
      lymphoid cell types have been reported to receive context-dependent inputs from
      the Notch pathway that regulate their differentiation and function. Progress in
      the field will continue to bring fundamental information about hematopoiesis and
      practical insights into the potential to modulate Notch signaling for therapeutic
      purposes.

PMID- 22399341
TI  - Notch signaling in lung development and disease.
AB  - Notch signaling plays an essential role in development and homeostasis of
      multiple organs including the lung. Dysregulation of Notch signaling has been
      implicated in various lung diseases including lung cancer. Here we review
      functions of Notch signaling in coordinating events during lung development, such
      as early proximodistal fate generation and branching, airway epithelial cell fate
      specification, alveogenesis and pulmonary vascular development. We also discuss
      roles of Notch in chronic obstructive pulmonary disease, progressive pulmonary
      fibrosis, pulmonary arterial hypertension, asthma and lung cancer.

PMID- 22399336
TI  - The role of Adams in Notch signaling.
AB  - Regulated intramembrane proteolysis (RIP) is a highly conserved signaling
      paradigm whereby membrane-bound signaling proteins are cleaved in their
      transmembrane region and then released into the cytoplasm to act as signaling
      molecules. In most if not all cases intramembrane cleavage is preceded and
      regulated by a membrane proximal cleavage step called 'ectodomain shedding'. Here
      we will review the role of ectodomain shedding in RIP of the NOTCH signaling
      pathway, a highly conserved cell-cell communication pathway that mediates cell
      fate decisions during development and in adult tissues.

PMID- 22399343
TI  - Notch signaling and the developing skeleton.
AB  - Notch signaling is an important regulator of skeletogenesis at multiple
      developmental stages. The Notch signaling pathway is involved in the promotion of
      somite segmentation, patterning and differentiation into sclerotome pre
      chondrogenic cells to allow for appropriate axial skeleton development. In
      addition, studies performed in vitro and in vivo demonstrate that Notch signaling
      suppresses chondrogenic and osteoblastic differentiation and negatively regulates
      osteoclast formation and proliferation. Through the use of in vitro and in vivo
      approaches, Notch signaling has been shown to regulate somitogenesis,
      chondrogenesis, osteoblastogenesis and osteoclastogenesis that ultimately affect
      skeletogenesis. Dysregulation of Notch signaling results in congenital skeletal
      malformations that could reveal therapeutic potential.

PMID- 22399342
TI  - The role of Notch signaling in kidney development and disease.
AB  - The kidney is the body's filter, responsible for the removal of metabolic waste
      and the excretion or reabsorption of electrolytes to control blood composition
      and pH balance. The functional unit of this filter is the nephron, whose
      segmented architecture has been largely conserved in form and function throughout
      eukaryotic evolution. Not surprisingly, the core developmental pathways that
      regulate the formation of the nephron have also been conserved. In particular,
      the Notch signaling pathway functions in both primitive and advanced nephrons to
      pattern domains required for the kidney's diverse functions. In this chapter, we
      will discuss the role that Notch plays in directing cell fate decisions during
      embryonic development of the pronephros and metanephros. We will go on to discuss
      the later role of Notch signaling as a cyst-suppressor and the consequences of
      aberrant or absent Notch activity in disease and cancer. The work discussed here
      highlights the fundamental importance of Notch during development and homeostasis
      of the kidney and underlies the need for mechanistic understanding of its role
      towards the treatment of human disease.

PMID- 22399344
TI  - Notch signaling and the developing skin epidermis.
AB  - The innermost (basal) layer of the skin epidermis consists of proliferative
      progenitors which give rise to multiple differentiating layers providing a
      barrier that keeps the inside of the body moist and protects the body from
      outside assaults by physical, environmental and biological factors. The epidermis
      is maintained throughout life through the proliferation of stem cells and
      differentiation of their progeny. Notch signaling pathway is a highly conserved
      molecular network that plays an essential role in cell fate determination during
      embryogenesis and also in postnatal life. Data from ongoing studies indicate that
      Notch signaling orchestrates the process of epidermal differentiation and
      proliferation through the sequential activity of different Notch ligands,
      receptors and downstream pathways.

PMID- 22399345
TI  - Notch signaling and the developing hair follicle.
AB  - Notch function in the hair follicle has been mainly studied by use of transgenic
      mice carrying either loss or gain of function mutations in various members of the
      pathway. These studies revealed that whereas embryonic development of the hair
      follicle can be achieved without Notch, its postnatal development requires an
      intact Notch signaling in the hair bulb and the outer root sheath. Among the many
      roles played by Notch in the hair follicle, two can be highlighted: in the bulge,
      Notch controls a cell fate switch in hair follicle stem cells or their
      progenitors, preventing them from adopting an epidermal fate. In the hair bulb,
      Notch controls cell differentiation, ensuring the proper development of every
      layer of the hair shaft and inner root sheath. Notch function in the hair
      follicle is both cell autonomous and cell non autonomous and involves
      intercellular communication between adjacent layers.

PMID- 22399346
TI  - Notch signaling and the developing inner ear.
AB  - Sensory hair cells (HCs) and their associated nonsensory supporting cells (SCs)
      exhibit a typical mosaic pattern in each of the sensory patches in the inner ear.
      Notch signaling has been considered to conduct the formation of this mosaic
      pattern through one of its famous functions, known as 'lateral inhibition'. The
      two Notch ligands Delta-like1 and Jagged2 are believed to act synergistically at
      the stage of cell diversification in mammals. In addition, many current studies
      suggest that Notch signaling has another inductive, but not inhibiting, role in
      the determination of the prosensory region, which precedes the cell
      diversification of HCs and SCs and Jagged1 is thought to be an essential ligand
      in this process. Earlier in ear development, the first cell fate determination
      begins with the delamination of the neuroblasts from the otic epithelium. The
      delaminated neuroblasts migrate and coalesce to form cochleovestibular ganglion.
      Notch signaling pathway is thought to function during the delamination through
      its lateral inhibitory mechanism. Recently, many experiments examining Notch
      related gene expression patterns and direct functional analyses of genes have
      revealed multiple important functions of Notch in inner ear development. Here, we
      survey a series of studies and discuss the issues that remain to be elucidated in
      the future.

PMID- 22399347
TI  - Notch signaling in cancer stem cells.
AB  - Subpopulations of cancer cells with stem cell-like characteristics, termed cancer
      stem cells, have been identified in a wide range of human cancers. Cancer stem
      cells are defined by their ability to self-renew as well as recapitulate the
      original heterogeneity of cancer cells in culture and in serial xenotransplants.
      Not only are cancer stem cells highly tumorigenic, but these cells are implicated
      in tumor resistance to conventional chemotherapy and radiotherapy, thus
      highlighting their significance as therapeutic targets. Considerable similarities
      have been found between cancer stem cells and normal stem cells on their
      dependence on certain signaling pathways. More specifically, the core stem cell
      signaling pathways, such as the Wnt, Notch and Hedgehog pathways, also critically
      regulate the self-renewal and survival of cancer stem cells. While the oncogenic
      functions of Notch pathway have been well documented, its role in cancer stem
      cells is just emerging. In this chapter, we will discuss recent advances in
      cancer stem cell research and highlight the therapeutic potential of targeting
      Notch in cancer stem cells.

PMID- 22399348
TI  - Notch signaling pathway and cancer metastasis.
AB  - Cancer metastasis is the leading cause of cancer-related deaths all over the
      world at present. Accumulated researches have demonstrated that cancer metastasis
      is composed of a series of successive incidents, mainly including epithelial
      mesenchymal transition (EMT), malignant cell migration, resistance to anoikis,
      and angiogenesis and lymphangiogenesis processes. However, the complicated
      cellular and molecular mechanisms underlying and modulating these processes have
      not been well elucidated. Thus, studies on cancer metastasis mechanism may
      propose possibilities to therapeutically interfere with signaling pathways
      required for each step of cancer metastasis, therefore inhibiting the outgrowth
      of distant metastasis of tumors. Recent insights have linked the Notch signaling
      pathway, a critical pathways governing embryonic development and maintaining
      tumor stemness, to cancer metastasis. This chapter highlights the current
      evidence for aberration of the Notch signaling in metastasis of tumors such as
      osteosarcoma, breast cancer, prostate cancer, and melanoma. In these studies,
      Notch activity seems to participate in cancer metastasis by modulating the EMT,
      tumor angiogenesis processes, and the anoikis-resistance of tumor cells.
      Therefore, manipulating Notch signaling may represent a promising alternative/
      complement therapeutic strategy targeting cancer metastasis besides cancer
      stemness.

PMID- 22399349
TI  - Notch, apoptosis and cancer.
AB  - Proper embryonic development and normal tissue homeostasis require a series of
      molecular processes, regulating cell growth, differentiation and apoptosis.
      Perturbation in any of these processes invariably contributes to the development
      of cancer. In particular, defects in apoptosis are seen in virtually all types of
      human cancers. The Notch pathway plays an important role in cell fate
      determination in both embryonic development and organ homeostasis. Not
      surprisingly, Notch also plays a role in cancer when it is dysregulated. In this
      chapter, we will explore how Notch signaling interacts with key pathways that
      regulate apoptosis in cancer. Particularly, we will focus on the relationship
      between Notch and proteins responsible for activation of the caspase pathway.
      Notch regulates apoptosis through extensive networks, involving cell cycle,
      growth and survival pathways. Thus, we will also examine how apoptosis is
      modulated by the crosstalk between Notch and other signaling pathways such as
      p53, NF-kappaB and PI3K-Akt pathways.

PMID- 22399350
TI  - Ligand-dependent Notch signaling in vascular formation.
AB  - The Notch signaling pathway is a critical component of vascular formation and
      morphogenesis in both development and disease. Compelling evidence indicates that
      Notch signaling is required for the induction of arterial-cell fate during
      development and for the selection of endothelial tip and stalk cells during
      sprouting angiogenesis. In mammals, two of the four Notch receptors (Notch1 and
      Notch4) and three of the five Notch ligands (Jagged1, Dll1 and Dll4) are
      predominantly expressed in vascular endothelial cells and are important for many
      aspects of vascular biology. During arterial cell-fate selection and
      angiogenesis, the roles of Notch1 and Notch4 are thought to be similar and the
      role of Dll4 is well-characterized. However, the molecular mechanisms that
      determine the functional similarities and differences of Notch ligands in
      vascular endothelial cells remain largely unknown; consequently, additional
      research is needed to elucidate the ligand-specific functions and mechanisms
      associated with Notch activation in the vascular endothelium. Results from recent
      studies indicate that Dll1 and Dll4 have distinct roles in the specification and
      maintenance of arterial cell identity, while Dll4 and Jagged1 have opposing
      effects on tip- and stalk-cell selection during sprouting angiogenesis. This
      chapter will focus on the newly discovered, distinct roles of several Notch
      ligands in the regulation of blood vessel formation and will provide perspectives
      for future research in the field.

PMID- 22399352
TI  - Notch signaling and breast cancer.
AB  - It has been more than two decades since Notch has been identified as an oncogene
      in mouse mammary tumor virus-infected mice. Since this discovery, activated Notch
      signaling and up-regulation of tumor-promoting Notch target genes have been
      observed in human breast cancer. In addition, high expression of Notch ligands
      and receptors has been shown to correlate with poor outcome in this malignancy.
      Notch affects multiple cellular processes including stem cell maintenance, cell
      fate specification, differentiation, proliferation, motility and survival.
      Perturbation of these activities is a hallmark of carcinogenesis and evidence
      continues to accumulate that aberrant Notch activity influences breast cancer
      progression through these processes.

PMID- 22399351
TI  - Notch and the p53 clan of transcription factors.
AB  - Notch 1 to 4 and the p53 clan, comprising p53, p63 and p73 plus numerous isoforms
      thereof, are gene transcription regulators that are critically involved in
      various aspects of cell differentiation, stem cell maintenance and tumour
      suppression. It is thus perhaps no surprise that extensive crosstalk between the
      Notch and p53 pathways is implemented during these processes. Typically, Notch
      together with p53 and even more so with transactivation competent p63 or p73,
      drives differentiation, whereas Notch combined with transactivation impaired p63
      or p73 helps maintain undifferentiated stem cell compartments. With regard to
      cancer, it seems that Notch acts as a tumour suppressor in cellular contexts
      where Notch signalling supports p53 activation and both together can bring on its
      way an anti-proliferative programme of differentiation, senescence or apoptosis.
      In contrast, Notch often acts as an oncoprotein in contexts where it suppresses
      p53 activation and activity and where differentiation is unwanted. It is no
      accident that the latter pathways-the inhibition by Notch of p53 and
      differentiation-are operative in somatic stem cells as well as in tumour cells.

PMID- 22399353
TI  - Notch signaling and malignant melanoma.
AB  - Increasing evidence indicates that Notch signaling contributes to physiologic
      processes, including development, differentiation and tumorigenesis, either as a
      tumor promoter or suppressor depending on the cellular context, level of
      expression and cross-talk with other signaling systems. Notch signalling has been
      implicated in the regulation of self-renewal of adult stem cells and
      differentiation of precursors along a specific cell line in normal embryonic
      development and organogenesis. There is also evidence that signaling through
      Notch receptors regulates cell proliferation and cell survival in several types
      of cancer including malignant melanoma, with opposing results depending on the
      tissue context. Tumor progression/metastasis of malignant melanoma are
      complicated processes that require multiple cellular events, including cell
      proliferation, survival, migration and invasion. Notch signaling appears to be a
      promising system for new therapeutic targets for the treatment of melanoma and
      perhaps the prevention of melanoma metastasis.

PMID- 22399354
TI  - Notch-signaling and nonmelanoma skin cancer: an ancient friend, revisited.
AB  - In humans and other species, Notch-signaling is of critical importance for
      carcinogenesis in several organs, including the skin. Interestingly, Notch
      signaling appears to exert opposite roles in skin carcinogenesis as compared to
      carcinogenesis in other tissues. While the Notch1 receptor (Notch1) acts as a
      proto-oncogene in most tissues, it has been shown that Notch1 deletion in
      epidermal keratinocytes causes skin carcinogenesis. Recent results indicate that
      loss of Notch1 is not involved in the initiating event of multistage skin
      carcinogenesis, but acts as a skin cancer-promoting event. Moreover, recent
      findings underline the importance of multiple other factors, including the
      microenvironment, for Notch signaling in skin carcinogenesis. It can be
      speculated that pharmacologic modulation of Notch signaling may be an interesting
      target for the prevention and therapy of skin cancer.

PMID- 22399355
TI  - Notch signaling and intestinal cancer.
AB  - In recent years, a substantial body of evidence has accumulated to support the
      notion that signaling pathways known to be important during embryonic development
      play important roles in regulating self-renewing tissues and tumorigenesis. In
      this context, Notch signaling is now recognized as essential for maintaining
      progenitor/ stem cell population as well as for regulating cell lineage
      differentiation in the normal intestinal mucosa. Many studies have also showed
      that Notch signaling is constitutively activated in colorectal cancer and its
      inhibition is able to suppress the cell growth and sensitize cancer cells to
      treatment-induced apoptosis. Therefore, discovery of the role of gamma-secretase
      in the Notch signaling activation has prompted intensive research on the
      potential use of gamma-secretase inhibitors in the treatment of colon cancer.
      This chapter reviews the current understanding and research findings of the role
      of Notch signaling in intestinal homeostasis and colorectal cancer and discusses
      the possible Notch targeting approaches as novel molecular therapy for intestinal
      cancer.

PMID- 22399356
TI  - Notch signaling and brain tumors.
AB  - Human brain tumors are a heterogenous group of neoplasms occurring inside the
      cranium and the central spinal cord. In adults and children, astrocytic glioma
      and medulloblastoma are the most common subtypes of primary brain tumors. These
      tumor types are thought to arise from cells in which Notch signaling plays a
      fundamental role during development. Recent findings have shown that Notch
      signaling is dysregulated and contributes to the malignant potential of these
      tumors. Growing evidence point towards an important role for cancer stem cells in
      the initiation and maintenance of glioma and medulloblastoma. In this chapter we
      will cover the present findings of Notch signaling in human glioma and
      medulloblastoma and try to create an overall picture of its relevance in the
      pathogenesis of these tumors.

PMID- 22399358
TI  - Genetic diversity and differentiation of Michelia maudiae (Magnoliaceae) revealed
      by nuclear and chloroplast microsatellite markers.
AB  - Michelia maudiae Dunn. is a Magnoliaceae species threatened by habitat
      destruction and over-exploitation. Genetic diversity and differentiation,
      population contribution to total diversity and allelic/haplotypic richness, and
      the relative importance of pollen- and seed-mediated gene flow were investigated
      in nine populations (192 individuals) of M. maudiae using nuclear and chloroplast
      microsatellites to further our understanding of the genetic structure and
      evolutionary history of this tree species and to provide a genetic perspective
      for its conservation. The species had strong pollen mediated gene flow in the
      past. The ratio of pollen to seed gene flow was 25.4. Three clusters from the
      western, central, and eastern China were identified by both chloroplast and
      nuclear microsatellites. Western populations at Xiaodanjiang and Daoxian were
      phylogenetically divergent from the remaining populations and might be
      particularly important for the conservation of this species. The populations of
      Xiaodanjiang, Daoxian, and Minjiangyuan made positive contribution to the total
      diversity and allelic/haplotypic richness, and were worthy of being conserved
      with priority. In the central cluster, population at Laopengding should be
      protected since it harbored the greatest genetic diversity.

PMID- 22399357
TI  - Notch inhibition as a promising new approach to cancer therapy.
AB  - The Notch pathway powerfully influences stem cell maintenance, development and
      cell fate and is increasingly recognized for the key roles it plays in cancer.
      Notch promotes cell survival, angiogenesis and treatment resistance in numerous
      cancers, making it a promising target for cancer therapy. It also crosstalks with
      other critical oncogenes, providing a means to affect numerous signaling pathways
      with one intervention. While the gamma-secretase inhibitors are the only form of
      Notch inhibitors in clinical trials, other forms of Notch inhibition have been
      developed or are theoretically feasible. In this chapter we review the rationales
      for Notch inhibition in cancer and then discuss in detail the various modalities
      for Notch inhibition, both current and speculative.

PMID- 22399359
TI  - Hospitalisations and costs relating to ambulatory care sensitive conditions in
      Ireland.
AB  - BACKGROUND: Ambulatory care sensitive conditions (ACSCs) are conditions for which
      the provision of timely and effective outpatient care can reduce the risks of
      hospitalisation by preventing, controlling or managing a chronic disease or
      condition. AIMS: The aims of this study were to report on ACSCs in Ireland, and
      to provide a baseline for future reference. METHODS: Using HIPE, via Health Atlas
      Ireland, inpatient discharges classified as ACSCs using definitions from the
      Victorian ACSC study were extracted for the years 2005-2008. Direct methods of
      standardisation allowed comparison of rates using the EU standard population as a
      comparison for national data, and national population as comparison for county
      data. Costs were estimated using diagnosis-related groups. RESULTS: The directly
      age-standardised discharge rate for ACSC-related discharges increased slightly,
      but non-significantly, from 15.40 per 1,000 population in 2005 to 15.75 per 1,000
      population in 2008. The number of discharges increased (9.5%) from 63,619 in 2005
      to 69,664 in 2008, with the estimated associated hospital costs increasing
      (31.5%) from <euro>267.8 million in 2005 to <euro>352.2 million in 2008. Across
      the country, there was considerable variation in the discharge rates for the Top
      10 ACSCs for the years 2005-2008. Significantly lower rates of hospitalisation
      were observed in more urban areas including Cork, Dublin and Galway. The most
      common ACSC in 2008 was diabetes with complications (29.8%). CONCLUSIONS: The
      variation in rates observed indicates the scope of reducing hospitalisations and
      associated costs for ACSCs, across both adult's and children's services and
      particularly in relation to diabetes complications.

PMID- 22399361
TI  - Adolescent attachment insecurity and parasympathetic functioning predict future
      loss adjustment.
AB  - Losing a close relationship is highly stressful and a robust predictor of major
      depression in adolescents. The current study examined relationships between
      attachment insecurity, parasympathetic nervous system activity, indexed by
      respiratory sinus arrhythmia (RSA), and adolescent adjustment to the loss of a
      close social partner. Adolescents with more attachment anxiety to their mother at
      age 14 were more likely to report poorer adjustment to a subsequent loss than
      adolescents with less attachment anxiety. Attachment avoidance interacted with
      stress-induced changes in RSA to predict loss adjustment. Among adolescents with
      higher RSA in response to the stressor, those with more attachment avoidance
      reported better loss adjustment, whereas among adolescents with lower RSA in
      response to the stressor, those with more attachment avoidance reported poorer
      loss adjustment. In sum, the combination of attachment insecurity and stress
      induced changes in RSA predicted how well adolescents adjusted to a loss.

PMID- 22399360
TI  - Explicit and implicit approach motivation interact to predict interpersonal
      arrogance.
AB  - Self-reports of approach motivation are unlikely to be sufficient in
      understanding the extent to which the individual reacts to appetitive cues in an
      approach-related manner. A novel implicit probe of approach tendencies was thus
      developed, one that assessed the extent to which positive affective (versus
      neutral) stimuli primed larger size estimates, as larger perceptual sizes co
      occur with locomotion toward objects in the environment. In two studies (total N
      = 150), self-reports of approach motivation interacted with this implicit probe
      of approach motivation to predict individual differences in arrogance, a broad
      interpersonal dimension previously linked to narcissism, antisocial personality
      tendencies, and aggression. The results of the two studies were highly parallel
      in that self-reported levels of approach motivation predicted interpersonal
      arrogance in the particular context of high, but not low, levels of implicit
      approach motivation. Implications for understanding approach motivation, implicit
      probes of it, and problematic approach-related outcomes are discussed.

PMID- 22399362
TI  - Outgroup helping as a tool to communicate ingroup warmth.
AB  - The authors extend previous research on the effects of metastereotype activation
      on outgroup helping by examining in more detail the role of group impression
      management motives and by studying direct helping (i.e., helping the outgroup
      believed to hold a negative view of the ingroup). Data from three experiments
      provided full support for the communicative nature of direct outgroup helping by
      demonstrating that outgroup helping in response to a negative metastereotype was
      predicted by participants' concern for the image of their ingroup, but not by
      their self-image concerns. Moreover, group image concerns predicted outgroup
      helping but not ingroup helping and predicted outgroup helping only when a
      negative metastereotype was activated, compared with a positive metastereotype,
      or a (negative or positive) autostereotype. The results also ruled out an
      alternative explanation in terms of denying the self-relevance of the
      metastereotype.

PMID- 22399363
TI  - Single-session percutaneous alcohol sclerotherapy for the treatment of isolated
      draining intrahepatic biliary duct in a five-month-old liver transplant
      recipient.
AB  - The present paper describes the first reported successful use of a single session
      of percutaneous alcohol sclerotherapy for the treatment of an excluded segmental
      biliary duct in a five-month-old left lateral liver recipient. A concomitant
      stricture of the hepaticojejunostomy was also successfully treated using standard
      percutaneous balloon dilatation. The patient has remained in good general
      condition for the next 26 months.

PMID- 22399364
TI  - Local staging of prostate cancer with MRI.
AB  - Accurate local staging of prostate cancer is essential for patient management    
      decisions. Conventional and evolving magnetic resonance imaging (MRI)    
      techniques, such as diffusion- weighted imaging, dynamic contrast-enhanced MRI,  
      and MR spectroscopy, are promising techniques in prostate cancer imaging. In   
      this article, we will review the current applications of conventional and    
      advanced MRI techniques in the local staging of prostate cancer.

PMID- 22399365
TI  - Placement of duodenal stents across the duodenal papilla may predispose to acute
      pancreatitis: a retrospective analysis.
AB  - PURPOSE: To evaluate retrospectively the incidence, predictive factors, and
      management of acute pancreatitis which develops following placement of duodenal
      stents in patients with malignant gastroduodenal obstruction. MATERIALS AND
      METHODS: Among 242 patients with symptomatic malignant gastroduodenal obstruction
      successfully treated with duodenal stent placement, acute pancreatitis occurred
      in 10 patients (4.1%) at 1-7 days after stent placement. Univariate and
      multivariate analyses were performed to evaluate factors predictive of acute
      pancreatitis. Management of acute pancreatitis was also evaluated. RESULTS: Ten
      patients with acute pancreatitis presented with abdominal pain and distention
      with vomiting at 1-7 days after stent placement, and seven patients developed
      acute jaundice. Pancreatitis resolved in four patients with a regime of fasting
      and intravenous nutrition. The remaining six cases were managed with percutaneous
      transhepatic cholangiography and drain (PTCD) placement. Univariate analysis
      showed that acute pancreatitis was associated with stent location in the
      descending duodenum (P = 0.001) and with stents bridging the duodenal papilla (P
      < 0.001). Multivariate analysis demonstrated that the presence of a stent
      bridging the duodenal papilla (odds ratio, 18.48; 95% confidence interval, 2.298-
      148.48; P = 0.006) was an independent predictor of acute pancreatitis.
      CONCLUSION: Acute pancreatitis is an uncommon early complication of duodenal
      stent placement in patients with malignant gastroduodenal obstruction. In this
      group of patients, acute pancreatitis was associated with stent location in the
      descending duodenum and occurred in patients with stents bridging the duodenal
      papilla; the latter may be the most important predictor of acute pancreatitis.
      Jaundice can be managed conservatively or with PTCD.

PMID- 22399366
TI  - Transient ischemic dilation for coronary artery disease in quantitative analysis
      of same-day sestamibi myocardial perfusion SPECT.
AB  - BACKGROUND: Transient ischemic dilation (TID) of the left ventricle in myocardial
      perfusion SPECT (MPS) has been shown to be a clinically useful marker of severe
      coronary artery disease (CAD). However, TID has not been evaluated for 99mTc
      sestamibi rest/stress protocols (Mibi-Mibi). We aimed to develop normal limits
      and evaluate diagnostic power of TID ratio for Mibi-Mibi scans. METHODS: TID
      ratios were automatically derived from static rest/stress MPS (TID) and gated
      rest/stress MPS from the end-diastolic phase (TID(ed)) in 547 patients who
      underwent Mibi-Mibi scans [215 patients with correlating coronary angiography and
      332 patients with low likelihood (LLk) of CAD]. Scans were classified as severe
      (>= 70% stenosis in proximal left anterior descending (pLAD) artery or left main
      (LM), or >= 90% in >= 2 vessels), mild to moderate (>= 90% stenosis in 1 vessel
      or >= 70%-90% in >= 1 vessel except pLAD or LM), and normal (<70% stenosis or LLk
      group). Another classification based on the angiographic Duke prognostic CAD
      index (DI) was also applied: DI >= 50, 30 <= DI < 50 and DI < 30 or LLk group.
      RESULTS: The upper normal limits were 1.19 for TID and 1.23 for TID(ed) as
      established in 259 LLk patients. Both ratios increased with disease severity (P <
      .0001). Incidence of abnormal TID increased from 2% in normal patients to >36% in
      patients with severe CAD. Similarly, when DI was used to classify disease
      severity, the average ratios showed significant increasing trend with DI increase
      (P < .003); incidence of abnormal TID also increased with increasing DI. The
      incidence of abnormal TID in the group with high perfusion scores significantly
      increased compared to the group with low perfusion scores (stress total perfusion
      deficit, TPD < 3%) (P < .0001). The sensitivity for detecting severe CAD improved
      for TID when added to mild to moderate perfusion abnormality (3% <= TPD < 10%):
      71% vs 64%, P < .05; and trended to improve for TID(ed)/TID(es): 69% vs 64%, P =
      .08, while the accuracy remained consistent if abnormal TID was considered as a
      marker in addition to stress TPD. Similar results were obtained when DI was used
      for the definition of severe CAD (sensitivity: 76% vs 66%, P < .05 when TID was
      combined with stress TPD). CONCLUSION: TID ratios obtained from gated or ungated
      Mibi-Mibi MPS and are useful markers of severe CAD.

PMID- 22399367
TI  - Another conclusion on "85% of maximal age-predicted heart rate is not a valid
      endpoint for exercise treadmill testing".

PMID- 22399369
TI  - Medicare spending, mortality rates, and quality of care.
AB  - We applied instrumental variable analysis to a sample of 388,690 Medicare
      beneficiaries predicted to be high-cost cases to estimate the effects of medical
      care use on the relative odds of death or experiencing an avoidable
      hospitalization in 2006. Contrary to conclusions from the observational
      geographic variations literature, the results suggest that greater medical care
      use is associated with statistically significant and quantitatively meaningful
      health improvements: a 10% increase in medical care use is associated with a 8.4%
      decrease in the mortality rate and a 3.8% decrease in the rate of avoidable
      hospitalizations.

PMID- 22399368
TI  - Metformin use among individuals at risk for type 2 diabetes.
AB  - Excess total and cardiovascular morbidity and mortality remain very high among
      those with type 2 diabetes versus those without diabetes. Clinical trials to
      lower blood glucose have been disappointing probably because the participants
      were too late in the natural history of diabetes and already had extensive
      vascular disease. Insulin resistance measured simply by elevated fasting blood
      insulin is an early marker of beta-cell stress and peripheral insulin resistance.
      Metformin will prevent development of diabetes among patients with impaired
      fasting glucose but only for the short term. Metformin reduces risk of coronary
      heart disease. The drug is safe, low cost, and may also prevent cancer. The
      combination of diet and exercise followed by metformin in the early phase of
      "insulin resistance" may reduce or delay both atherosclerosis and
      arteriosclerosis complications associated with diabetes. Preventive therapy must
      begin much earlier than before clinical diagnosis of diabetes and aim to
      initially lower blood insulin levels or insulin resistance.

PMID- 22399370
TI  - The origin of the bacterial immune response.
AB  - Bacteriophages are probably the oldest viruses, having appeared early during
      bacterial evolution. Therefore, bacteria and bacteriophages have a long history
      of co-evolution in which bacteria have developed multiple resistance mechanisms
      against bacteriophages. These mechanisms, that are very diverse and are in
      constant evolution, allow the survival of the bacteria. Bacteriophages have
      adapted to bacterial defense systems, devised strategies to evade these anti
      phage mechanisms and restored their infective capacity. In this chapter, we
      review the bacterial strategies that hinder the phage infection as well as the
      counter-defense mechanisms developed.

PMID- 22399371
TI  - The evolution of self during the transition to multicellularity.
AB  - The notion of ' self' is intrinsically linked to the concepts of identity and
      individuality. During evolutionary transitions in individuality-such as, for
      instance, during the origin of the first cell, the origin of the eukaryotic cell
      and the origin of multicellular individuals-new kinds of individuals emerged from
      the interaction of previously independent entities. The question discussed here
      is: How can new types of individuals with qualities that cannot be reduced to the
      properties of their parts be created at a higher level? This question is
      addressed in the context of the transition to multicellularity and using the
      volvocine green algae-a group of closely related unicellular and multicellular
      species with various degrees of physiological and reproductive unity-as a model
      system. In this chapter, we review our framework to addressing the evolution of
      individuality during the transition to multicellularity, focusing on the
      reorganization of general life-traits and cellular processes and the cooption of
      environmentally-induced responses.

PMID- 22399372
TI  - Glyconectin glycans as the self-assembling nano-molecular-velcrosystem mediating
      self-nonself recognition and adhesion implicated in evolution of
      multicellularity.
AB  - The goal of this chapter is to make a specific contribution about glyconectin
      glycan as the self-assembling nano-molecular-velcro system mediating initial
      steps of self-nonself recognition and cell adhesion in Porifera, the first
      descendants of the most simple primordial multicellular organisms. Two original
      findings will be described: (i) Velcro like concept based on highly polyvalent
      and specific intermolecular glycan to glycan associations with extremely low
      affinity of the single binding site and (ii) novel structures of the large and
      newly emerging family of glyconectin like glycan molecules. The emphasis will be
      put on the interdisciplinary approach for studying structure to function
      relationship at the different size scale levels by combining the knowledge and
      technologies (instrumentation and methods) of physics, chemistry, biology and
      mathematics. Applying such strategy which is crossing the boundaries of different
      science disciplines enabled us to develop a new Atomic Force Microscopy (AFM)
      based nano-bio-technology and perform the first quantitative measurements of
      intermolecular binding forces at the single molecular level under physiological
      conditions. We propose that nano-velcro systems of the glyconectin glycans, which
      are the constituents on the cell surface that are the most exposed to the
      environment, were responsible for the molecular self-nonself recognition and
      adhesion processes that underpinned the emergence of multicellular life forms.

PMID- 22399373
TI  - Neglected biological features in cnidarians self-nonself recognition.
AB  - Cnidarian taxa, currently of the most morphologically simplest extant metazoans,
      exhibit many salient properties of innate immunity that are shared by most
      Animalia. One hallmark constituent of immunity exhibit by most cnidarians is
      histocompatibility, marked by wide spectrum of allogeneic and xenogeneic effector
      arms, progressing into tissue fusions or inflammatory rejections. Scientific
      propensity on cnidarians immunity, while discussing historecognition as the
      ground for immunity in these organisms, concentrates on host-parasitic and
      disease oriented studies, or focuses on genome approaches that search for gene
      homologies with the vertebrates. Above tendency for mixing up between
      historecognition and host-parasitic/disease, highlights a serious obstacle for
      the progress in our understanding of cnidarian immunobiology. Here I critically
      overview four 'forgotten' cnidarian immune features, namely, specificity,
      immunological memory, allogeneic maturation and natural chimerism, presenting
      insights into perspectives that are prerequisite for any discussion on cnidarian
      evolution. It is evident that cnidarian historecognition embraces elements that
      the traditional field of vertebrate immunology has never encountered (i.e.,
      variety of cytotoxic outcomes, different types of effector mechanisms, chimerism,
      etc.). Also, cnidarian immune features dictating that different individuals
      within the same species seem to respond differently to the same immunological
      challenge, is far from that recorded in the vertebrates' adaptive immunity. While
      above features may be connected to host-parasitic and disease phenomena and
      effector arms, they clearly attest to their unique critical roles in shaping
      cnidarians historecognition, calling for improved distinction between
      historecognition and host-response/ disease disciplines. The research on
      cnidarians immunity still suffers from the lack of accepted synthesis of what
      historecognition is or does. Mounting of an immune response against conspecifics
      or xenogeneic organisms should therefore be clearly demarcated from other paths
      of immunity, till cnidarian innate immunity as a whole is expounded.

PMID- 22399374
TI  - Intracellular inflammatory sensors for foreign invaders and substances of self
      origin.
AB  - In order to survive, all organisms must recognize and eliminate foreign invaders
      such as infectious pathogens, chemicals, ultraviolet rays, metabolites and
      damaged or transformed self-tissues, as well as allogenic organs in cases of
      transplantation. Recent research in innate immunity has elucidated that there are
      versatile inflammatory sensors on spatiotemporal 'sentry duty' that recognize
      substances derived from both 'nonself' and 'self', e.g., Toll-like receptors,
      retinoic acid-inducible gene-I-like receptors, nucleotide oligomerization domain
      like receptors and c-type lectin receptors. Having acquired high-level functions
      through the development of multiple molecules, higher organisms have established
      both extracellular and intracellular sensors that can discriminate danger
      associated molecular patterns from promiscuous, but biologically similar,
      molecular patterns. In addition, 'loss-of-function' or 'gain-of-function'
      mutations in these inflammatory sensors have been linked (at least in part) with
      the etiology and severity of autoimmune diseases, autoinflammatory diseases and
      immunocompromised diseases in humans. Further studies focusing on the role of
      these inflammatory sensors in the development of immune disorders would highlight
      new avenues for the development of novel diagnostic and therapeutic applications
      with regard to these diseases.

PMID- 22399375
TI  - Nonself perception in plant innate immunity.
AB  - The ability to distinguish' self' from 'nonself' is the most fundamental aspect
      of any immune system. The evolutionary solution in plants to the problems of
      perceiving and responding to pathogens involves surveillance of nonself, damaged
      self and altered-self as danger signals. This is reflected in basal resistance or
      nonhost resistance, which is the innate immune response that protects plants
      against the majority of pathogens. In the case of surveillance of nonself, plants
      utilize receptor-like proteins or -kinases (RLP/Ks) as pattern recognition
      receptors (PRRs), which can detect conserved pathogen/microbe-associated
      molecular pattern (P/MAMP) molecules. P/MAMP detection serves as an early warning
      system for the presence of a wide range of potential pathogens and the timely
      activation of plant defense mechanisms. However, adapted microbes express a suite
      of effector proteins that often interfere or act as suppressors of these
      defenses. In response, plants have evolved a second line of defense that includes
      intracellular nucleotide binding leucine-rich repeat (NB-LR)-containing
      resistance proteins, which recognize isolate-specific pathogen effectors once the
      cell wall has been compromised. This host-immunity acts within the species level
      and is controlled by polymorphic host genes, where resistance protein-mediated
      activation of defense is based on an 'altered-self' recognition mechanism.

PMID- 22399376
TI  - How did flowering plants learn to avoid blind date mistakes? Self-incompatibility
      in plants and comparisons with nonself rejection in the immune response.
AB  - Self-incompatibility (SI) is a common form of genetically-controlled mate
      selection that prevents mating between closely related plants of the same
      species. SI occurs in about half of all flowering plant species. It has been
      studied extensively in the Papaveraceae (poppy), Brassicaceae (Arabidopsis,
      cabbage etc), Solanaceae (potato, tomato etc), Plantaginaceae (snapdragon) and
      Rosaceae (apple, cherry and peach etc). The self-recognition inherent in self
      incompatibility has similarities with animal and plant immunity systems giving
      rise to speculation that the systems are related. Both systems display balancing
      selection, 'self/nonself' recognition, high polymorphism, high specificity and
      there are also some similarities in the rejection mechanisms deployed in the two
      systems. Whether these systems have diverged from a common predecessor is
      discussed, however similarities may be driven more by biological problems and the
      available molecular machinery to solve them than by an evolutionary relationship.

PMID- 22399377
TI  - Signaling pathways that regulate life and cell death: evolution of apoptosis in
      the context of self-defense.
AB  - Programmed Cell Death is essential for the life cycle of many organisms. Cell
      death in multicellular organisms can occur as a consequence of massive damage
      (necrosis) or in a controlled form, through engagement of diverse biochemical
      programs. The best well known form of programmed cell death is apoptosis.
      Apoptosis occurs in animals as a consequence of a variety of stimuli including
      stress and social signals and it plays essential roles in morphogenesis and
      immune defense. The machinery of apoptosis is well conserved among animals and it
      is composed of caspases (the proteases which execute cell death), adapter
      proteins (caspase activators), Bcl-2 family proteins and Inhibitor of Apoptosis
      Proteins (IAPs). We will describe in this chapter the main apoptotic pathways in
      animals: the extrinsic (death receptor-mediated), the intrinsic/mitochondrial and
      the Granzyme B pathway. Other forms of non-apoptotic Programmed Cell Death which
      occur in animals will also be discussed. We will summarize the current knowledge
      about apoptotic-like and other forms of cell death in other organisms such as
      plants and protists.Additionally, we will discuss the hypothesis that apoptosis
      originated as part of a host defense mechanism. We will explore the similarities
      between the protein complexes which mediate apoptosis (apoptosomes) and complexes
      involved in immunity: inflammasomes. Additional functions of apoptotic proteins
      related to immune function will be summarized, in an effort to explore the
      evolutionary origins of cell death.

PMID- 22399378
TI  - Sensing necrotic cells.
AB  - Multicellular organisms have developed ways to recognize potentially life
      threatening events (danger signals). Classically, danger signals have been
      defined as exogenous, pathogen-associated molecular patterns (PAMPs) such as
      bacterial cell wall components (e.g., lipopolysaccharide and peptideglycan) or
      viral DNA/RNA. PAMPs interact with dedicated receptors on immune cells, so-called
      pattern recognition receptors (PRRs) and activate immune systems. A well-known
      family of PRRs is the toll-like receptors (TLRs) in which each member recognizes
      a specific set of PAMPs. However, not only exogenous pathogens but also several
      endogenous molecules released from necrotic cells (damaged self) also activate
      immune systems. These endogenous adjuvants are called damage-associated molecular
      patterns (DAMPs). It has been reported that high-mobility group box 1 protein
      (HMGB1), uric acid, heat shock proteins (HSPs) and nucleotides act as endogenous
      adjuvants. DAMPs are recognized by specific receptors (danger receptors)
      expressed mainly on antigen-presenting cells such as dendritic cells and
      macrophages and induce cell maturation and the production of inflammatory
      cytokines by activating the NF-kB pathway. In this chapter, we will review danger
      signals released from necrotic cells and its recognition receptors.

PMID- 22399379
TI  - Sensing endoplasmic reticulum stress.
AB  - This chapter provides an overview of our present understanding of mechanisms of
      sensing protein folding status and endoplasmic reticulum (ER) stress in
      eukaryotic cells. The ER folds and matures most secretory and transmembrane
      proteins. Mis- or unfolded proteins are sensed by specialized ER stress sensors,
      such as IRE1, PERK and ATF6, which initiate several cellular responses and
      signaling pathways to restore ER homeostasis. These intracellular signaling
      events are called the unfolded protein response (UPR). Here we focus on how ER
      stress and protein folding status in the ER are sensed by the ER stress sensors
      by summarizing results from recent structural, biochemical and genetic
      approaches.

PMID- 22399380
TI  - Autophagy and self-defense.
AB  - Autophagy is a highly conserved mechanism which is essential for the maintenance
      of cellular homeostasis in response to cellular stress. Autophagy has been
      conserved from yeast to humans as a quality control process that is involved in
      the recognition and turnover of damaged proteins and organelles. It is also a
      response mechanism to nutrient starvation. In mammals, autophagy is involved in
      antigen presentation, tolerance, inflammation and protection against
      neurodegenerative diseases. The decrease of autophagy during aging reduces the
      removal of damaged organelles and increases the accumulation of waste products in
      the cells. In this chapter, we review these aspects of autophagy along with their
      role in self-nonself distinction, their implication in innate and adaptive immune
      response, and its dysregulation in the pathology of certain inflammatory and
      autoimmune diseases.

PMID- 22399381
TI  - Viruses and host evolution: virus-mediated self identity.
AB  - Virus evolution has become a topic that involves population based selection. Both
      quasispecies based populations and reticulated mosaic exchange of populations of
      genetic elements are now well established. This has led us to the understanding
      that a cooperative consortia can be a crucial aspect of virus driven evolution.
      Thus viruses exist in groups that can cooperate. However, consortial based
      evolution (group selection) has long been dismissed by evolutionary biologist.
      Recently, biocommunication theory has concluded that the evolution and editing of
      any code or language requires a consortial based process in order to adhere to
      pragmatic (context) requirements for meaning (in conflict with survival of the
      fittest concepts). This has led to the idea that viruses are the natural editors
      of biological codes or language. In this chapter, I present the view that the
      persistence of virus information in their host provides a natural process of host
      code editing that is inherently consortial. Since persistence requires mechanisms
      to attain stability and preclude competition, it also provided mechanisms that
      promote group identity. Accordingly, I review the viral origins of addiction
      modules and how these affect both persistence and group identity. The concepts
      emerging from addiction module based group identity are then generalized and
      applied to social identity systems as well. I then examine the prokaryotes and
      the involvement of viral elements in the emergence of their group identity
      systems (biofilms). Here, integrating dsDNA agents prevailed. In the eukaryotes,
      however, a large shift in virus-host evolution occurred in which the role of
      dsDNA agents was diminished but the role of retroviruses and retroposons was
      greatly enhanced. These agents provided greatly expanded and network based
      regulatory complexity that was controlled by sensory inputs. From this
      perspective, the role of virus in the origin of the adaptive immune system is
      then outlined. I then consider human evolution from the perspective of the great
      HERV colonization. The origin of a large social brain able to support the
      learning of language is presented from this viral perspective. The role of
      addiction modules in the origin of extended social bonding of humans is outlined
      and applied to the emergence of language as a system of group identity.

PMID- 22399382
TI  - The evolution of adaptive immunity.
AB  - The concept of adaptive immunity suggests de novo generation in each individual
      of extremely large repertoires of diversified receptors and selective expansion
      of receptors that match the antigen/pathogen. Accordingly, adaptive immune system
      is also called "anticipatory". It allows each individual to have a unique
      repertoire of immune receptors corresponding to its life history. The memory of
      an antigen gets encoded in the clonal composition of the organism's immune cells
      instead of being encoded in the genome. Consequently, the immune response to
      repeated encounter with the same antigen becomes stronger, a phenomenon called
      immunological memory. Elements of adaptive immunity are found at all taxonomical
      levels, whereas in vertebrates, adaptive mechanisms have become the cornerstone
      of the immune system. In jaw vertebrates, adaptive immune receptors of T and B
      lymphoid cells belong to immunoglobulin superfamily and are created by
      rearrangement of gene segments. In jawless vertebrates lamprey and hagfish,
      recombination of leucine-rich repeat modules is used to form variable lymphocyte
      receptors. Striking functional similarity of the cellular and humoral branches of
      these systems suggests similar driving forces underlying their development.

PMID- 22399383
TI  - Epigenetic code and self-identity.
AB  - Epigenetics is a new and expanding science that studies the chromatin-based
      regulation of gene expression. It is achieving considerable importance,
      especially with regard to developmental mechanisms that drive cell and organ
      differentiation, as well as in all those biological processes that involve
      response and adaptation to environmental stimuli. One of the most interesting
      biological questions concerning animals, especially human beings, is the ability
      to distinguish self from nonself. This ability has developed throughout
      evolution, both as the main function of the immune system, which defends against
      attack by foreign organisms and at the level of consciousness of oneself as an
      individual, one of the highest functions of the brain that enables social life.
      Here we will attempt to dissect the epigenetic mechanisms involved in
      establishing these higher functions and describe some alterations of the
      epigenetic machinery responsible for the impairment of correct self-recognition
      and self-identity.

PMID- 22399384
TI  - Viral immunomodulatory proteins: usurping host genes as a survival strategy.
AB  - Large DNA-containing viruses encode a plethora of gene products that are
      homologous to cellular proteins and key for their success in nature. During the
      millions of years of co-evolution with their respective hosts, viruses have
      extensively captured cellular genes, frequently duplicated them and insidiously
      shaped them to yield optimized specific molecules capable of either mimicking or
      interfering with the original host function and/or of executing novel tasks. A
      vast number of these gene products have become an integral part of the elaborated
      counteracting immune evasion strategies developed by viruses to withstand with
      the selective evolutionary pressure imposed by the host immune system.
      Cytomegaloviruses (CMVs) constitute an outstanding example of the many and varied
      encoded proteins directed to modulate both innate and adaptive immune responses,
      which determine their ability to establish life-long latency with sporadic
      shedding in their hosts. This chapter focuses on the current understanding of
      those genes encoded by human CMV (HCMV) with a known homology to cell proteins of
      the immune system. A systematic study of these genes, in addition to unraveling
      specific virus-host interactions, may supply valuable tools to dissect the
      molecular basis of immune responses.

PMID- 22399385
TI  - The emergence of the major histocompatilibility complex.
AB  - The Major Histocompatibility Complex (MHC) is a genomic region that contains
      genes that encode proteins involved with antigen presentation and, therefore,
      plays an important role in the adaptive immune system. The origin of these genes
      was probably an ancestral MHC that appeared before the emergence of the adaptive
      immune system and contained genes related to immunity. The organization of MHC
      genes varies in different groups of vertebrates; although, there are some
      characteristics that are maintained in all groups, which indicates that they
      confer some evolutionary advantage: Organization of the genes to form clusters
      and genetic polymorphisms. The study of how the MHC appeared during evolution and
      how it is organized in different species can help us clarify what features are
      essential in their participation in self-nonself recognition.

PMID- 22399387
TI  - Human pancreatic polypeptide in a phospholipid-based micellar formulation.
AB  - PURPOSE: Pancreatic polypeptide (PP) has important glucoregulatory functions and
      thereby holds significance in the treatment of diabetes and obesity. However,
      short plasma half-life and aggregation propensity of PP in aqueous solution,
      limits its therapeutic application. To address these issues, we prepared and
      characterized a formulation of PP in sterically stabilized micelles (SSM) that
      protects and stabilizes PP in its active conformation. METHODS: PP-SSM was
      prepared by incubating PP with SSM dispersion in buffer. Peptide-micelle
      association and freeze-drying efficacy of the formulation was characterized in
      phosphate buffers with or without sodium chloride using dynamic light scattering,
      fluorescence spectroscopy and circular dichroism. The degradation kinetics of PP
      SSM in presence of proteolytic enzyme was determined using HPLC and bioactivity
      of the formulation was evaluated by in vitro cAMP inhibition study. RESULTS: PP
      self-associated with SSM and this interaction was influenced by presence/absence
      of sodium chloride in the buffer. The formulation was effectively lyophilized,
      demonstrating feasibility for its long-term storage. The stability of peptide
      against proteolytic degradation was significantly improved and PP in SSM retained
      its bioactivity in vitro. CONCLUSIONS: Self-association of PP with phospholipid
      micelles addressed the delivery issues of the peptide. This nanomedicine should
      be further developed for the treatment of diabetes.

PMID- 22399388
TI  - Treatment of experimental brain metastasis with MTO-liposomes: impact of fluidity
      and LRP-targeting on the therapeutic result.
AB  - PURPOSE: To test targeted liposomes in an effort to improve drug transport across
      cellular barriers into the brain. METHODS: Therefore we prepared Mitoxantrone
      (MTO) entrapping, rigid and fluid liposomes, equipped with a 19-mer angiopeptide
      as ligand for LDL lipoprotein receptor related protein (LRP) targeting. RESULTS:
      Fluid, ligand bearing liposomes showed in vitro the highest cellular uptake and
      transcytosis and were significantly better than the corresponding ligand-free
      liposomes and rigid, ligand-bearing vesicles. Treatment of mice, transplanted
      with human breast cancer cells subcutaneously and into the brain, with fluid
      membrane liposomes resulted in a significant reduction in the tumor volume by
      more than 80% and in a clear reduction in drug toxicity. The improvement was
      mainly depended on liposome fluidity while the targeting contributed only to a
      minor degree. Pharmacokinetic parameters were also improved for liposomal MTO
      formulations in comparison to the free drug. So the area under the curve was
      increased and t(1/2) was extended for liposomes. CONCLUSION: Our data show that
      it is possible to significantly improve the therapy of brain metastases if MTO
      encapsulating, fluid membrane liposomes are used instead of free MTO. This effect
      could be further enhanced by fluid, ligand bearing liposomes.

PMID- 22399386
TI  - MHC signaling during social communication.
AB  - The major histocompatibility complex (MHC) has been known to play a critical role
      in immune recognition since the 1950s. It was a surprise, then, in the 1970s when
      the first report appeared indicating MHC might also function in social signaling.
      Since this seminal discovery, MHC signaling has been found throughout vertebrates
      and its known functions have expanded beyond mate choice to include a suite of
      behaviors from kin-biased cooperation, parent-progeny recognition to pregnancy
      block. The widespread occurrence of MHC in social signaling has revealed
      conserved behavioral-genetic mechanisms that span vertebrates and includes
      humans. The identity of the signal's chemical constituents and the receptors
      responsible for the perception of the signal have remained elusive, but recent
      advances have enabled the identification of the key components of the behavioral
      circuit. In this chapter we organize recent findings from the literature and
      discuss them in relation to four nonmutually exclusive models wherein MHC
      functions as a signal of (i) individuality, (ii) relatedness, (iii) genetic
      compatibility and (iv) quality. We also synthesize current mechanistic studies,
      showing how knowledge about the molecular basis of MHC signaling can lead to
      elegant and informative experimental manipulations. Finally, we discuss current
      evidence relating to the primordial functions of the MHC, including the
      possibility that its role in social signaling may be ancestral to its central
      role in adaptive immunity.

PMID- 22399389
TI  - Enhanced topical delivery of small hydrophilic or lipophilic active agents and
      epidermal growth factor by fractional radiofrequency microporation.
AB  - PURPOSE: To evaluate the ability of a novel radiofrequency (RF) microporation
      technology based on ablation of the skin barrier to enhance topical delivery of
      active ingredients METHODS: The influence of RF fluence and the molecular size of
      the absorbent on the permeation enhancement was confirmed by in vitro skin
      permeation study using Franz diffusion cells. The improved skin rejuvenation
      effects, such as depigmentation and anti-wrinkle effects, by enhanced topical
      delivery of alpha-bisabolol and epidermal growth factor (EGF) through the RF
      microchannels were investigated in photo-damaged skin. RESULTS: The cumulative
      amounts of active ingredients through the RF microporated skin were significantly
      increased. Topically applied alpha-bisabolol after RF microporation induced rapid
      onset of skin whitening and significantly increased the DeltaL-value of UVB
      induced hyperpigmented melanin hairless mouse skin. In addition, wrinkle
      formation after topical application of EGF with RF microporation was
      significantly reduced and prevented after 12 weeks, and all parameters involving
      wrinkles in a replica analysis were similar to those in the negative control.
      CONCLUSIONS: RF microporation enhances the topical delivery of active ingredients
      with high molecular weight or of small hydrophilic or lipophilic molecules. Thus,
      this technology can effectively improve photo-induced hyperpigmentation and
      wrinkle formation by enhancing topical delivery of active agents.

PMID- 22399392
TI  - Thermosensor systems in eubacteria.
AB  - Four different mechanisms have evolved in eubacteria to comply with changes in
      the environmental temperature. The underlying genetic mechanisms regulate gene
      expression at transcriptional, translational and posttranslational level. The
      high temperature response (HTR) is a reaction on increases in temperature and is
      mainly used by pathogenic bacteria when they enter their mammalian host. The
      temperature of 37 degrees C causes induction of the virulent genes the products
      of which are only needed in this environment. The heat shock response (HSR) is
      induced by any sudden increase in temperature, allows the bacterial cell to adapt
      to this environmental stress factor and is shut off after adaptation. In a
      similar way the low temperature response (LTR) is a reaction to a new environment
      and leads to the constant expression of appropriate genes. In contrast, the cold
      shock response (CSR) includes turn off of the cold shock genes after adaptation
      to the low temperature. Sensors of temperature changes are specific DNA regions,
      RNA molecules or proteins and conformational changes have been identified as a
      common motif.

PMID- 22399391
TI  - Spinal cord stimulation: neurophysiological and neurochemical mechanisms of
      action.
AB  - Chronic neuropathic pain can significantly reduce quality of life and place an
      economic burden on individuals and society. Spinal cord stimulation (SCS) is an
      alternative approach to the treatment of neuropathic pain when standard
      pharmacological agents have failed. However, an improved understanding of the
      mechanisms by which SCS inhibits pain is needed to enhance its clinical utility.
      This review summarizes important findings from recent studies of SCS in animal
      models of neuropathic pain, highlights current understanding of the spinal
      neurophysiological and neurochemical mechanisms by which SCS produces an
      analgesic effect, and discusses the potential clinical applicability of these
      findings and future directions for research.

PMID- 22399390
TI  - Role of nitric oxide in cluster headache.
AB  - Nitric oxide (NO) is an important molecule in headache pathophysiology. NO
      regulates vascular tone and acts as a potent vasodilator, and thus participates
      in regulating blood flow. NO is also considered to play a role in processing
      sensory information and pain sensitization. In this article, we review the role
      of NO in one of the primary headache disorders, cluster headache (CH). The
      pathophysiology of CH is still not completely understood. A multifactorial
      genesis where NO is likely to be involved is probable. The level of NO production
      has been shown to correlate with disease activity in several inflammatory
      disorders, such as cystitis, multiple sclerosis, and cerebral lupus
      erythematosus. In this article, the issue of whether similar circumstances apply
      for CH and also the role of NO in the pathophysiology of CH in a wider
      perspective are discussed.

PMID- 22399393
TI  - Molecular plant volatile communication.
AB  - Plants produce a wide array of volatile organic compounds (VOCs) which have
      multiple functions as internal plant hormones (e.g., ethylene, methyl jasmonate
      and methyl salicylate), in communication with conspecific and heterospecific
      plants and in communication with organisms of second (herbivores and pollinators)
      and third (enemies of herbivores) trophic levels. Species specific VOCs normally
      repel polyphagous herbivores and those specialised on other plant species, but
      may attract specialist herbivores and their natural enemies, which use VOCs as
      host location cues. Attraction of predators and parasitoids by VOCs is considered
      an evolved indirect defence, whereby plants are able to indirectly reduce biotic
      stress caused by damaging herbivores. In this chapter we review these
      interactions where VOCs are known to play a crucial role. We then discuss the
      importance of volatile communication in self and nonself detection. VOCs are
      suggested to appear in soil ecosystems where distinction of own roots from
      neighbours roots is essential to optimise root growth, but limited evidence of
      above-ground plant self-recognition is available.

PMID- 22399394
TI  - Primary processes in sensory cells: current advances.
AB  - In the course of evolution, the strong and unremitting selective pressure on
      sensory performance has driven the acuity of sensory organs to its physical
      limits. As a consequence, the study of primary sensory processes illustrates
      impressively how far a physiological function can be improved, if the survival of
      a species depends on it. Sensory cells that detect single-photons, single
      molecules, mechanical motions on a nanometer scale, or incredibly small
      fluctuations of electromagnetic fields have fascinated physiologists for a long
      time. It is a great challenge to understand the primary sensory processes on a
      molecular level. This chapter points out some important recent developments in
      the search for primary processes in sensory cells that mediate touch perception,
      hearing, vision, taste, olfaction, as well as the analysis of light polarization
      and the orientation in the Earth's magnetic field. The data are screened for
      common transduction strategies and common transduction molecules, an aspect that
      may be helpful for researchers in the field.

PMID- 22399395
TI  - Chemical communication in insects: the peripheral odour coding system of
      Drosophila melanogaster.
AB  - Animals use their chemosensory systems to detect and discriminate among chemical
      cues in the environment. Remarkable progress has recently been made in our
      knowledge of the molecular and cellular basis of chemosensory perception in
      insects, based largely on studies in the vinegar fly Drosophila melanogaster.
      This progress has been possible due to the identification of gene families for
      olfactory receptors, the use of electro-physiological recording techniques on
      sensory neurons, the manifold of genetic manipulations that are available in this
      species and insights from several insect model systems. The superfamilies of
      olfactory receptor proteins, the Or genes and the more recently discovered IR
      genes, represent the essential elements in olfactory coding, endowing olfactory
      receptor neurons with their abilities to respond to specific sets of odorants or
      pheromones. General odorants activate receptors in a combinatorial fashion, but
      some receptors are narrowly tuned to pheromones or to carbon dioxide.
      Surprisingly, olfactory receptors in insects are biochemically quite different to
      those in mammals and do not appear to signal via classical G protein pathways but
      rather via ionotropic mechanisms. Here we review the past decade of intensive
      research since the discovery of the first insect olfactory receptors in 1999,
      focusing on the molecules and cells that underly peripheral olfactory perception
      in Drosophila.

PMID- 22399396
TI  - Eusocial evolution and the recognition systems in social insects.
AB  - Eusocial species, animals which live in colonies with a reproductive division of
      labor, typically have closed societies, in which colony members are allowed entry
      and nonmembers, including animals of the same species, are excluded. This implies
      an ability to discriminate colony members ("self") from nonmembers ("nonself").
      We draw analogies between this type of discrimination and MHC-mediated cellular
      recognition in vertebrates. Recognition of membership in eusocial colonies is
      typically mediated by differences in the surface chemistry between members and
      nonmembers and we review studies which support this hypothesis. In rare
      instances, visual signals mediate recognition. We highlight the need for better
      understanding of which surface compounds actually mediate recognition and for
      further work on how differences between colony members and nonmembers are
      perceived.

PMID- 22399397
TI  - Odor and pheromone sensing via chemoreceptors.
AB  - Evolutionally, chemosensation is an ancient but yet enigmatic sense. All
      organisms ranging from the simplest unicellular form to the most advanced
      multicellular creature possess the capability to detect chemicals in the
      surroundings. Conversely, all living things emit some forms of smells, either as
      communicating signals or as by-products of metabolism. Many species (from worms,
      insects to mammals) rely on the olfactory systems which express a large number of
      chemoreceptors to locate food and mates and to avoid danger. Most chemoreceptors
      expressed in olfactory organs are G-protein coupled receptors (GPCRs) and can be
      classified into two major categories: odorant receptors (ORs) and pheromone
      receptors, which principally detect general odors and pheromones, respectively.
      In vertebrates, these two types of receptors are often expressed in two distinct
      apparatuses: The main olfactory epithelium (MOE) and the vomeronasal organ (VNO),
      respectively. Each olfactory sensory neuron (OSN) in the MOE typically expresses
      one type of OR from a large repertoire. General odors activate ORs and their host
      OSNs (ranging from narrowly- to broadly-tuned) in a combinatorial manner and the
      information is sent to the brain via the main olfactory system leading to
      perception of smells. In contrast, pheromones stimulate relatively narrowly-tuned
      receptors and their host VNO neurons and the information is sent to the brain via
      the accessory olfactory system leading to behavioral and endocrinological
      changes. Recent studies indicate that the functional separation between these two
      systems is blurred in some cases and there are more subsystems serving
      chemosensory roles. This chapter focuses on the molecular and cellular mechanisms
      underlying odor and pheromone sensing in rodents, the best characterized
      vertebrate models.

PMID- 22399398
TI  - Identifying self- and nonself-generated signals: lessons from electrosensory
      systems.
AB  - This chapter provides a short review of the mechanisms used by electroreceptive
      fish to discriminate self- from nonself-generated signals. Electroreception is
      used by animals to detect objects of electric impedance different from the water,
      to detect natural electrogenic sources and to communicate signals between
      conspecifics. Electroreceptive animals may generate electric fields either with
      the purpose of electrically illuminating the neighborhood or as an epiphenomenon
      of other functions. In addition, the presence of the fish body as a conductive
      object in a scene funnels the current flow and, consequently, animal movements
      also generate signals by changing the body shape or the spatial relationship of
      the body with the surrounding objects. Therefore, mechanisms for discrimination
      between self and externally generated signals are very important for constructing
      a coherent representation of the environment. Some mechanisms facilitate and
      stream the flow of signals carried by the self-generated electric field. Others
      are designed to reject unwanted interference coming from self-generated movements
      or even the self-generated electric field. Finally, more complex operations
      involving sensory motor integration are used for discriminating between self- and
      conspecific- generated communication signals. Despite the evolutionary distance
      between animals endowed with electric sense, mechanisms for self-identification
      reappear with few differences between species. This suggests that many of the
      possible strategies are present in vertebrates may be found in these fish.
      Therefore, we have much to learn about self recognition from the study of
      electroreception.

PMID- 22399399
TI  - Magnetoreception.
AB  - Animals can use the direction of the magnetic field as a compass and the
      intensity of the magnetic field as a component of the navigational 'map'. Two
      fundamentally different mechanisms of magnetoreception have been discussed: (1)
      light-dependent reactions in specialized photopigments lead to radical pairs,
      with the ratio singlet/ triplet depending on the molecule's alignment with
      respect to the ambient magnetic field and (2) reactions involving small crystals
      of magnetite, a specific iron oxide of biogen origin. The first mechanism
      provides birds and possibly amphibians and insects with compass information; the
      second, which can theoretically provide animals with information on direction and
      intensity, appears to mediate intensity information in birds and compass
      information e.g., in mammals. Little is known about the magnetoreception
      mechanisms in other animals.

PMID- 22399401
TI  - The evolution of vertebrate color vision.
AB  - Color vision is conventionally defined as the ability of animals to reliably
      discriminate among objects and lights based solely on differences in their
      spectral properties. Although the nature of color vision varies widely in
      different animals, a large majority of all vertebrate species possess some color
      vision and that fact attests to the adaptive importance this capacity holds as a
      tool for analyzing the environment. In recent years dramatic advances have been
      made in our understanding of the nature of vertebrate color vision and of the
      evolution of the biological mechanisms underlying this capacity. In this chapter
      I review and comment on these advances.

PMID- 22399400
TI  - The molecular basis of mechanosensory transduction.
AB  - Multiple senses, including hearing, touch and osmotic regulation, require the
      ability to convert force into an electrical signal: A process called
      mechanotransduction. Mechanotransduction occurs through specialized proteins that
      open an ion channel pore in response to a mechanical stimulus. Many of these
      proteins remain unidentified in vertebrates, but known mechanotransduction
      channels in lower organisms provide clues into their identity and mechanism.
      Bacteria, fruit flies and nematodes have all been used to elucidate the molecules
      necessary for force transduction. This chapter discusses many different
      mechanical senses and takes an evolutionary approach to review the proteins
      responsible for mechanotransduction in various biological kingdoms.

PMID- 22399402
TI  - Transforming the vestibular system one molecule at a time: the molecular and
      developmental basis of vertebrate auditory evolution.
AB  - We review the molecular basis of auditory development and evolution. We propose
      that the auditory periphery (basilar papilla, organ of Corti) evolved by
      transforming a newly created and redundant vestibular (gravistatic) endorgan into
      a sensory epithelium that could respond to sound instead of gravity. Evolution
      altered this new epithelia's mechanoreceptive properties through changes of hair
      cells, positioned the epithelium in a unique position near perilymphatic space to
      extract sound moving between the round and the oval window, and transformed its
      otolith covering into a tympanic membrane. Another important step in the
      evolution of an auditory system was the evolution of a unique set of "auditory
      neurons" that apparently evolved from vestibular neurons. Evolution of mammalian
      auditory (spiral ganglion) neurons coincides with GATA3 being a transcription
      factor found selectively in the auditory afferents. For the auditory information
      to be processed, the CNS required a dedicated center for auditory processing, the
      auditory nuclei. It is not known whether the auditory nucleus is ontogenetically
      related to the vestibular or electroreceptive nuclei, two sensory systems found
      in aquatic but not in amniotic vertebrates, or a de-novo formation of the rhombic
      lip in line with other novel hindbrain structures such as pontine nuclei. Like
      other novel hindbrain structures, the auditory nuclei express exclusively the
      bHLH gene Atoh1, and loss of Atoh1 results in loss of most of this nucleus in
      mice. Only after the basilar papilla, organ of Corti evolved could efferent
      neurons begin to modulate their activity. These auditory efferents most likely
      evolved from vestibular efferent neurons already present. The most simplistic
      interpretation of available data suggest that the ear, sensory neurons, auditory
      nucleus, and efferent neurons have been transformed by altering the developmental
      genetic modules necessary for their development into a novel direction conducive
      for sound extraction, conduction, and processing.

PMID- 22399404
TI  - Changing senses: chemosensory signaling and primate evolution.
AB  - Sensory organs provide key, and in many cases species-specific, information that
      allows animals to effectively forage, find mates and avoid hazards. The primary
      sensors for the vertebrate senses of vision, taste and smell are G-protein
      coupled receptors (GPCRs) expressed by sensory receptor cells that initiate
      intracellular signal transduction cascades in response to activation by
      appropriate stimuli. The identification of sensory GPCRs and their related
      downstream transduction components from a variety of species has provided an
      essential tool for understanding the molecular evolution of sensory systems.
      Expansion of the number of genes encoding sensory GPCRs has, in some cases,
      expanded the repertoire of signals that animals detect, allowing them to occupy
      new niches, while in other cases evolution has favored a reduction in the
      repertoire of receptors and their cognate signal transduction components when
      these signals no longer provide a selective advantage. This review will focus on
      recent studies that have identified molecular changes in smell, taste and
      pheromone detection during primate evolution.

PMID- 22399405
TI  - Molecules and mating: positive selection and reproductive behaviour in primates.
AB  - Sexual reproduction is generally thought to be more costly than asexual
      reproduction. However, it does have the advantage of accelerating rates of
      adaptation through processes such as recombination and positive selection.
      Comparative studies of the human and nonhuman primate genomes have demonstrated
      that positive selection has played an important role in the evolutionary history
      of humans and other primates. To date, many dozens of genes, thought to be
      affected by positive selection, have been identified. In this chapter, we will
      focus on genes that are associated with mating behaviours and reproductive
      processes, concentrating on genes that are most likely to enhance reproductive
      success and that also show evidence of positive selection. The genes encode
      phenotypic features that potentially influence mate choice decisions or impact
      the evolution and function of genes involved in the perception and regulation of,
      and the response to, phenotypic signals. We will also consider genes that
      influence precopulatory behavioural traits in humans and nonhuman primates, such
      as social bonding and aggression. The evolution of post-copulatory strategies
      such as sperm competition and selective abortion may also evolve in the presence
      of intense competition and these adaptations will also be considered. Although
      behaviour may not be solely determined by genes, the evidence suggests that the
      genes discussed in this chapter have some influence on human and nonhuman primate
      behaviour and that positive selection on these genes results in some degree of
      population differentiation and diversity.

PMID- 22399406
TI  - Immune systems evolution.
AB  - Animals and plants have a complex and effective immune system that protect them
      from invading microorganisms. The mechanisms of immunity are evolutionarily
      selected throughout host-pathogen interaction to be tolerant to self-antigens and
      to recognize nonself molecular patterns. Plants and animals share a germ line
      encoded diversity of receptors capable of nonself recognition. Somatic
      rearranging of immunological receptors emerges at early stages of vertebrate
      evolution, allowing these animals to generate an almost unlimited diversity of
      receptors. Nevertheless, this recombinational system came with a high price: The
      potential for self-reactivity. In this chapter we will discuss the differences
      and the striking similarities of the immune mechanisms across different taxa in
      the context of evolution and the selective pressures that favoured the
      development of the adaptive immune system and the lymphoid organs.

PMID- 22399407
TI  - Involvement of sirtuins in life-span and aging related diseases.
AB  - Since healthy aging remains one of the ideals of modern society, both, the
      identification of the underlying molecular mechanisms and interventions regarding
      the aging process are of considerable interest. Among the mechanisms currently
      being considered, the sirtuin family of histone deacetylases have been implicated
      to play a crucial role during the aging process both due to their requirement of
      NAD(+) as a cofactor for enzymatic activity, which determines a crucial link
      between sirtuins and the energy dependent regulation of gene transcription and
      their versatile target substrates mainly consisting of key regulators of
      metabolic, stress and cell cycle control. This chapter summarizes current
      evidences linking sirtuins to aging and outlines their potential as promising
      therapeutic targets for the treatment of age-related diseases.

PMID- 22399403
TI  - Neurobiology of sociability.
AB  - Sociability consists of behaviors that bring animals together and those that keep
      animals apart. Remarkably, while the neural circuitry that regulates these two
      "faces" of sociability differ from one another, two neurohormones, oxytocin (Oxt)
      and vasopressin (Avp), have been consistently implicated in the regulation of
      both. In this chapter the the structure and function of the Oxt and Avp systems,
      the ways in which affiliative and aggressive behavior are studied and the roles
      of Oxt and Avp in the regulation of sociability will be briefly reviewed.
      Finally, work implicating Oxt and Avp in sociability in humans, with a focus on
      neuropsychiatric disorders will be highlighted.

PMID- 22399409
TI  - The neural basis of semantic and episodic forms of self-knowledge: insights from
      functional neuroimaging.
AB  - Throughout evolution, hominids have developed greater capacity to think about
      themselves in abstract and symbolic ways. This process has reached its apex in
      humans with the construction of a concept of self as a distinct entity with a
      personal history. This chapter provides a review of recent functional
      neuroimaging studies that have investigated the neural correlates of such "higher
      level" aspects of the human self, focusing in particular on processes that allow
      individuals to consciously represent and reflect on their own personal attributes
      (semantic forms of self-knowledge) and experiences (episodic forms of self
      knowledge). These studies point to the medial prefrontal cortex (MPFC) as a key
      neural structure for processing various kinds of self-referential information. We
      speculate that the MPFC may mediate dynamic processes that appraise and code the
      self-relatedness or self-relevance of information. This brain region may thus
      play a key role in creating the mental model of the self that is displayed in our
      mind at a given moment.

PMID- 22399408
TI  - Molecular diversity of Dscam and self-recognition.
AB  - Cell recognition requires interactions through molecules located on cell surface.
      The insect homolog of Down syndrome cell adhesion molecule (Dscam) manifests huge
      molecular diversity in its extracellular domain. High-affinity Dscam-Dscam
      interactions only occur between isoforms that carry identical extracellular
      domains. Homophilic Dscam signaling can, thus, vary in strength depending on the
      compositions of Dscams present on the opposing cell surfaces. Dscam abundantly
      exists in the developing nervous system and governs arborization and proper
      elaboration of neurites. Notably, individual neurons may stochastically and
      dynamically express a small subset of Dscam isoforms such that any given neurite
      can be endowed with a unique repertoire of Dscams. This allows individual
      neurites to recognize their sister branches. Self-recognition leads to self
      repulsion, ensuring divergent migration of sister processes. By contrast, weak
      homophilic Dscam interactions may promote fasciculation of neurites that express
      analogous, but not identical, Dscams. Differential Dscam binding may provide
      graded cell recognition that in turn governs complex neuronal morphogenesis.

PMID- 22399410
TI  - Hallmarks of consciousness.
AB  - Consciousness, ranging from the primary, or perceptual, level to high levels that
      include a sense of self, can be identified in various organisms by a set of
      hallmarks that include behavioral, neural and phenomenal and/or informational.
      Behavioral hallmarks include those that indicate high cognitive abilities, such
      behavioral flexibility, verbal abilities, episodic memories, theory of mind,
      object constancy, transitive inference and multistability, all of which have been
      demonstrated in birds as well as in primates. Neural hallmarks include the
      thalamocortical model for mammals and similar circuitry in some nonmammalian
      taxa. Informational hallmarks include sensorimotor awareness, as provided by
      somatosensory and/or lateral line systems, which may form the basis for the sense
      of self and distinguishing self from nonself, as well as other sensory
      information, such as the richness and quantity of color and form information
      obtained by the visual system. The comparative method reveals a correlation of
      these different types of hallmarks with each other in their degree of
      development, which thus may be indicative of the level of consciousness present
      in a particular species.

PMID- 22399411
TI  - Parental occupational exposures and autism spectrum disorder.
AB  - Both self-report and industrial hygienist (IH) assessed parental occupational
      information were used in this pilot study in which 174 families (93 children with
      ASD and 81 unaffected children) enrolled in the Childhood Autism Risks from
      Genetics and Environment study participated. IH results indicated exposures to
      lacquer, varnish, and xylene occurred more often in the parents of children with
      ASD compared to the parents of unaffected children. Parents of children with ASD
      were more likely to report exposures to asphalt and solvents compared to parents
      of unaffected children. This study was limited by the small sample size, but
      results suggest that workplace exposures to some chemicals may be important in
      the etiology of ASD and deserve further investigation.

PMID- 22399413
TI  - Erratum to: How obedience of marriage rules may counteract genetic drift.

PMID- 22399412
TI  - Neurologic manifestations of systemic immunopathological diseases.
AB  - OPINION STATEMENT: Systemic immunopathological diseases with prominent
      neurological features include systemic lupus erythematosus (SLE), rheumatoid
      arthritis (RA), Sjogren's Syndrome (SS), and the systemic vasculitides. These
      systemic conditions can affect the nervous system in diverse ways. In many cases,
      the neurological disease heralds the onset of the systemic condition. Recognizing
      the pattern of neurological and systemic features of these conditions is critical
      in order to uncover the systemic condition in a timely manner. Although treatment
      of these conditions is usually directed at the underlying systemic disease,
      discovery of certain types of neurological involvement such as rapidly
      progressive mononeuritis multiplex may often necessitate more robust
      immunosuppressive therapy. The larger treatment trials addressing optimal therapy
      in these conditions are coordinated by rheumatologists and rarely address the
      neurological complications in isolation. As such, the evidence supporting
      neurology-specific therapy regimens is generally an extrapolation of findings
      that apply to the systemic condition as a whole and cannot be considered as Class
      I. Less severe neurological manifestations are often treated with glucocorticoids
      and immunosuppressive treatments such as azathioprine as a steroid-sparing
      strategy. More severe neurological involvement requires early and aggressive
      therapy with powerful immunosuppressive agents, often in combination with
      glucocorticoids and plasma exchange. Cyclophosphamide is the most established
      immunosuppressive therapy in this context but is limited by its toxicity.
      Rituximab is emerging as a highly promising alternative although its high cost is
      a major limitation.

PMID- 22399414
TI  - Witnesses in action: the effect of physical exertion on recall and recognition.
AB  - Understanding memory performance under different operational conditions is
      critical in many occupational settings. To examine the effect of physical
      exertion on memory for a witnessed event, we placed two groups of law-enforcement
      officers in a live, occupationally relevant scenario. One group had previously
      completed a high-intensity physical-assault exercise, and the other had not.
      Participants who completed the assault exercise showed impaired recall and
      recognition performance compared with the control group. Specifically, they
      provided significantly less accurate information concerning critical and
      incidental target individuals encountered during the scenario, recalled less
      briefing information, and provided fewer briefing updates than control
      participants did. Exertion was also associated with reduced accuracy in
      identifying the critical target from a lineup. These results support arousal
      based competition accounts proposing differential allocation of resources under
      physiological arousal. These novel findings relating to eyewitness memory
      performance have important implications for victims, ordinary citizens who become
      witnesses, and witnesses in policing, military, and related operational contexts.

PMID- 22399415
TI  - Learned predictiveness speeds visual processing.
AB  - When humans learn that the presence of a cue predicts the likelihood of an
      outcome, they can exploit this learned predictiveness, such that formation of
      subsequent associations between that cue and new outcomes is facilitated. Could
      such enhanced selection for association arise early enough to facilitate low
      level visual processing? In a test of this possibility, adult volunteers first
      engaged in a value-learning task involving faces that were differentially
      predictive of monetary wins or losses. Later, in a simple recognition task, these
      faces were briefly presented for a variable duration and then masked. The
      critical presentation duration needed to produce criterion-level recognition was
      measured to index the visual processing speed for each learned face. Critical
      duration was significantly shorter for stimuli with high learned predictiveness
      than for stimuli with low learned predictiveness, regardless of whether they were
      associated with wins or losses. These results show that neural mechanisms
      involved in predicting future outcomes are able to modulate visual processing
      efficiency, probably via cortical feedback processes.

PMID- 22399416
TI  - The oxidative phosphorylation system in mammalian mitochondria.
AB  - The chapter provides a review of the state of art of the oxidative
      phosphorylation system in mammalian mitochondria. The sections of the paper deal
      with: (i) the respiratory chain as a whole: redox centers of the chain and
      protonic coupling in oxidative phosphorylation (ii) atomic structure and
      functional mechanism of protonmotive complexes I, III, IV and V of the oxidative
      phosphorylation system (iii) biogenesis of oxidative phosphorylation complexes:
      mitochondrial import of nuclear encoded subunits, assembly of oxidative
      phosphorylation complexes, transcriptional factors controlling biogenesis of the
      complexes. This advanced knowledge of the structure, functional mechanism and
      biogenesis of the oxidative phosphorylation system provides a background to
      understand the pathological impact of genetic and acquired dysfunctions of
      mitochondrial oxidative phosphorylation.

PMID- 22399418
TI  - Mitochondrial Ca(2+) as a key regulator of mitochondrial activities.
AB  - Mitochondria play a central role in cell biology, not only as producers of ATP
      but also as regulators of the Ca(2+) signal. The translocation by respiratory
      chain protein complexes of H(+) across the ion-impermeable inner membrane
      generates a very large H(+) electrochemical gradient that can be employed not
      only by the H(+) ATPase to run the endoergonic reaction of ADP phosphorylation,
      but also to accumulate cations into the matrix. Mitochondria can rapidly take up
      Ca(2+) through an electrogenic pathway, the uniporter, that acts to equilibrate
      Ca(2+) with its electrochemical gradient, and thus accumulates the cation into
      the matrix, and they can release it through two exchangers (with H(+) and Na(+),
      mostly expressed in non-excitable and excitable cells, respectively), that
      utilize the electrochemical gradient of the monovalent cations to prevent the
      attainment of electrical equilibrium.The uniporter, due to its low Ca(2+)
      affinity, demands high local Ca(2+) concentrations to work. In different cell
      systems these high Ca(2+) concentration microdomains are generated, upon cell
      stimulation, in proximity of the plasma membrane and the sarco/endoplasmic
      reticulum Ca(2+) channels.Recent work has revealed the central role of
      mitochondria in signal transduction pathways: evidence is accumulating that, by
      taking up Ca(2+), they not only modulate mitochondrial activities but also tune
      the cytosolic Ca(2+) signals and their related functions. This review analyses
      recent developments in the area of mitochondrial Ca(2+) signalling and attempts
      to summarize cell physiology aspects of the mitochondrial Ca(2+) transport
      machinery.

PMID- 22399417
TI  - Physiology and pathophysiology of mitochondrial DNA.
AB  - Mitochondria are the only organelles in animal cells which possess their own
      genomes. Mitochondrial DNA (mtDNA) alterations have been associated with various
      human conditions. Yet, their role in pathogenesis remains largely unclear. This
      review focuses on several major features of mtDNA: (1) mtDNA haplogroup, (2)
      mtDNA common deletion, (3) mtDNA mutations in the control region or D-loop, (4)
      mtDNA copy number alterations, (5) mtDNA mutations in translational machinery,
      (6) mtDNA mutations in protein coding genes (7) mtDNA heteroplasmy. We will also
      discuss their implications in various human diseases.

PMID- 22399420
TI  - Mitochondria and reactive oxygen species. Which role in physiology and pathology?
AB  - Oxidative stress is among the major causes of toxicity due to interaction of
      Reactive Oxygen Species (ROS) with cellular macromolecules and structures and
      interference with signal transduction pathways. The mitochondrial respiratory
      chain, specially from Complexes I and III, is considered the main origin of ROS
      particularly under conditions of high membrane potential, but several other
      sources may be important for ROS generation, such as mitochondrial p66(Shc),
      monoamine oxidase, alpha-ketoglutarate dehydogenase, besides redox cycling of
      redox-active molecules. ROS are able to oxidatively modify lipids, proteins,
      carbohydrates and nucleic acids in mitochondria and to activate/inactivate
      signalling pathways by oxidative modification of redox-active factors. Cells are
      endowed with several defence mechanisms including repair or removal of damaged
      molecules, and antioxidant systems, either enzymatic or non-enzymatic. Oxidative
      stress is at the basis of ageing and many pathological disorders, such as
      ischemic diseases, neurodegenerative diseases, diabetes, and cancer, although the
      underlying mechanisms are not always completely understood.

PMID- 22399419
TI  - Mitochondria and nitric oxide: chemistry and pathophysiology.
AB  - Cell respiration is controlled by nitric oxide (NO) reacting with respiratory
      chain complexes, particularly with Complex I and IV. The functional implication
      of these reactions is different owing to involvement of different mechanisms.
      Inhibition of complex IV is rapid (milliseconds) and reversible, and occurs at
      nanomolar NO concentrations, whereas inhibition of complex I occurs after a
      prolonged exposure to higher NO concentrations. The inhibition of Complex I
      involves the reversible S-nitrosation of a key cysteine residue on the ND3
      subunit. The reaction of NO with cytochrome c oxidase (CcOX) directly involves
      the active site of the enzyme: two mechanisms have been described leading to
      formation of either a relatively stable nitrosyl-derivative (CcOX-NO) or a more
      labile nitrite-derivative (CcOX-NO (2) (-) ). Both adducts are inhibited, though
      with different K(I); one mechanism prevails on the other depending on the
      turnover conditions and availability of substrates, cytochrome c and O(2). SH
      SY5Y neuroblastoma cells or lymphoid cells, cultured under standard O(2) tension,
      proved to follow the mechanism leading to degradation of NO to nitrite. Formation
      of CcOX-NO occurred upon rising the electron flux level at this site,
      artificially or in the presence of higher amounts of endogenous reduced
      cytochrome c. Taken together, the observations suggest that the expression level
      of mitochondrial cytochrome c may be crucial to determine the respiratory chain
      NO inhibition pathway prevailing in vivo under nitrosative stress conditions. The
      putative patho-physiological relevance of the interaction between NO and the
      respiratory complexes is addressed.

PMID- 22399421
TI  - Uncoupling proteins: molecular, functional, regulatory, physiological and
      pathological aspects.
AB  - Uncoupling proteins are a subfamily of the mitochondrial anion carrier family.
      They are widespread in the whole eukaryotic world with a few exceptions and
      present tissue specific isoforms in higher organisms. They mediate purine
      nucleotide-sensitive free fatty acid-activated proton inward flux through the
      inner mitochondrial membrane. This proton flux occurs at the expense of the
      proton motive force build up by the respiration and weakens the coupling between
      respiration and ATP synthesis. In this chapter we describe current and reliable
      knowledge of uncoupling proteins. A new methodology allowing study of their
      activity and regulation during phosphorylating respiration is described. It has
      entitled us to assert that all uncoupling proteins share common mechanisms of
      activation and regulation. This is of the utmost importance in order to
      understand the physiological roles of UCPs as well as their participation in
      pathological processes since every role of the UCPs in every cell is an integral
      part of their function and regulation. The central role of reduction level of
      ubiquinone in the control of their regulation is well-argued. Their potential and
      reliable roles in thermogenesis, reactive oxygen species prevention and energy
      flow are discussed as well as their role in some pathological disorders.

PMID- 22399422
TI  - The mitochondrial pathways of apoptosis.
AB  - Apoptosis is a process of programmed cell death that serves as a major mechanism
      for the precise regulation of cell numbers, and as a defense mechanism to remove
      unwanted and potentially dangerous cells. Studies in nematode, Drosophila and
      mammals have shown that, although regulation of the cell death machinery is
      somehow different from one species to another, it is controlled by homologous
      proteins and involves mitochondria. In mammals, activation of caspases (cysteine
      proteases that are the main executioners of apoptosis) is under the tight control
      of the Bcl-2 family proteins, named in reference to the first discovered
      mammalian cell death regulator. These proteins mainly act by regulating the
      release of caspases activators from mitochondria. Although for a long time the
      absence of mitochondrial changes was considered as a hallmark of apoptosis,
      mitochondria appear today as the central executioner of apoptosis. In this
      chapter, we present the current view on the mitochondrial pathway of apoptosis
      with a particular attention to new aspects of the regulation of the Bcl-2
      proteins family control of mitochondrial membrane permeabilization: the
      mechanisms implicated in their mitochondrial targeting and activation during
      apoptosis, the function(s) of the oncosuppressive protein p53 at the mitochondria
      and the role of the processes of mitochondrial fusion and fission.

PMID- 22399423
TI  - Inherited mitochondrial disorders.
AB  - Though inherited mitochondrial disorders (MIDs) are most well known for their
      syndromic forms, for which widely known acronyms (MELAS, MERRF, NARP, LHON etc.)
      have been coined, the vast majority of inherited MIDs presents in a non-syndromic
      form. Since MIDs are most frequently multisystem disorders already at onset or
      during the disease course, a MID should be suspected if there is a combination of
      neurological and non-neurological abnormalities. Neurological abnormalities
      occurring as a part of a MID include stroke-like episodes, epilepsy, migraine
      like headache, movement disorders, cerebellar ataxia, visual impairment,
      encephalopathy, cognitive impairment, dementia, psychosis, hypopituitarism,
      aneurysms, or peripheral nervous system disease, such as myopathy, neuropathy, or
      neuronopathy. Non-neurological manifestations concern the ears, the endocrine
      organs, the heart, the gastrointestinal tract, the kidneys, the bone marrow, and
      the skin. Whenever there is an unexplained combination of neurological and non
      neurological disease in a patient or kindred, a MID should be suspected and
      appropriate diagnostic measures initiated. Genetic testing should be guided by
      the phenotype, the biopsy findings, and the biochemical results.

PMID- 22399424
TI  - Role of mitochondrial function in insulin resistance.
AB  - The obesity pandemic increases the prevalence of type 2 diabetes (DM2).DM2
      develops when pancreatic beta-cells fail and cannot compensate for the decrease
      in insulin sensitivity. How excessive caloric intake and weight gain cause
      insulin resistance has not completely been elucidated.Skeletal muscle is
      responsible for a major part of insulin stimulated whole-body glucose disposal
      and, hence, plays an important role in the pathogenesis of insulin resistance.It
      has been hypothesized that skeletal muscle mitochondrial dysfunction is involved
      in the accumulation of intramyocellular lipid metabolites leading to lipotoxicity
      and insulin resistance. However, findings on skeletal muscle mitochondrial
      function in relation to insulin resistance in human subjects are inconclusive.
      Differences in mitochondrial activity can be the result of several factors,
      including a reduced mitochondrial density, differences in insulin stimulated
      mitochondrial respiration, lower energy demand or reduced skeletal muscle
      perfusion, besides an intrinsic mitochondrial defect. The inconclusive results
      may be explained by the use of different techniques and study populations. Also,
      mitochondrial capacity is in far excess to meet energy requirements and therefore
      it may be questioned whether a reduced mitochondrial capacity limits
      mitochondrial fatty acid oxidation. Whether reduced mitochondrial function is
      causally related to insulin resistance or rather a consequence of the sedentary
      lifestyle remains to be elucidated.

PMID- 22399425
TI  - Mitochondria and diabetes. An intriguing pathogenetic role.
AB  - Mitochondria play a key role in energy metabolism and ATP production in many
      tissues, including skeletal muscle, cardiac muscle, brain and liver. Inherent
      disorders of mitochondria such as mDNA deletions cause major disruption of
      metabolism and can result in severe disease phenotypes. However, the incidence of
      such mDNA based disorders is extremely rare and cannot account for the dramatic
      rise in human metabolic diseases, which are characterised by defects in energy
      metabolism. Mitochondrial dysfunction characterized by reduced ATP generation and
      reduced mitochondrial number in skeletal muscle or reduced ATP generation and
      mitochondrial stimulus-secretion coupling in the pancreatic beta cell has been
      implicated in the pathology of chronic metabolic disease associated with type 2
      diabetes mellitus and also with aging. Additionally the generation of ROS from
      mitochondria and other cellular sources may interfere in insulin signaling in
      muscle, contributing to insulin resistance. Reduced mitochondrial oxidative
      capacity coupled with increased ROS generation underlies the accumulation of
      intramuscular fat, insulin resistance and muscle dysfunction in aging. We will
      review the molecular basis for optimal mitochondrial function or mechanisms of
      dysfunction and correlate with pathology of identified diseases and aging.

PMID- 22399426
TI  - Mitochondria and heart disease.
AB  - Mitochondria play a key role in the normal functioning of the heart, and in the
      pathogenesis and development of various types of heart disease. Physiologically,
      mitochondrial ATP supply needs to be matched to the often sudden changes in ATP
      demand of the heart, and this is mediated to a large extent by the mitochondrial
      Ca(2+) transport pathways allowing elevation of mitochondrial [Ca(2+)]
      ([Ca(2+)](m)). In turn this activates dehydrogenase enzymes to increase NADH and
      hence ATP supply. Pathologically, [Ca(2+)](m) is also important in generation of
      reactive oxygen species, and in opening of the mitochondrial permeability
      transition pore (MPTP); factors involved in both ischaemia-reperfusion injury and
      in heart failure. The MPTP has proved a promising target for protective
      strategies, with inhibitors widely used to show cardioprotection in experimental,
      and very recently human, studies. Similarly mitochondrially-targeted antioxidants
      have proved protective in various animal models of disease and await clinical
      trials. The mitochondrial Ca(2+) transport pathways, although in theory promising
      therapeutic targets, cannot yet be targeted in human studies due to non-specific
      effects of drugs used experimentally to inhibit them. Finally, specific
      mitochondrial cardiomyopathies due to mutations in mtDNA have been identified,
      usually in a gene for a tRNA, which, although rare, are almost always very severe
      once the mutation has exceeded its threshold.

PMID- 22399428
TI  - Mitochondria and cancer: a growing role in apoptosis, cancer cell metabolism and
      dedifferentiation.
AB  - At the beginning of the twentieth century, Otto Warburg demonstrated that cancer
      cells have a peculiar metabolism. These cells preferentially utilise glycolysis
      for energetic and anabolic purposes, producing large quantities of lactic acid.
      He defined this unusual metabolism "aerobic glycolysis". At the same time,
      Warburg hypothesised that a disruption of mitochondrial activities played a
      precise pathogenic role in cancer. Because of this so-called "Warburg effect",
      mitochondrial physiology and cellular respiration in particular have been
      overlooked in pathophysiological studies of cancer. Over time, however, many
      studies have shown that mitochondria play a fundamental role in cell death by
      apoptosis or necrosis. Moreover, metabolic enzymes of the Krebs cycle have also
      recently been recognised as oncosuppressors. Recently, a series of studies were
      undertaken to re-evaluate the role of oxidative mitochondrial metabolism in
      cancer cell growth and progression. Some of these data indicate that modulation
      of mitochondrial respiration may induce an arrest of cancer cell proliferation
      and differentiation (pseudodifferentiation) and/or or death, suggesting that
      iatrogenic manipulation of some mitochondrial activities may induce anticancer
      effects. Moreover, studying the role of mitochondria in cancer cell
      dedifferentiation/differentiation processes may allow further insight into the
      pathophysiology and therapy of so-called cancer stem cells.

PMID- 22399429
TI  - Mitochondria and aging.
AB  - Aging is a degenerative process that is associated with progressive accumulation
      of deleterious changes with time, reduction of physiological function and
      increase in the chance of disease and death. Studies in several species reveal a
      wide spectrum of alterations in mitochondria and mitochondrial DNA (mtDNA) with
      aging, including (1) increased disorganization of mitochondrial structure, (2)
      decline in mitochondrial oxidative phosphorylation (OXPHOS) function, (3)
      accumulation of mtDNA mutation, (4) increased mitochondrial production of
      reactive oxygen species (ROS) and (5) increased extent of oxidative damage to
      DNA, proteins, and lipids. In this chapter, we outline the common alterations in
      mitochondria of the aging tissues and recent advances in understanding the role
      of mitochondrial H(2)O(2) production and mtDNA mutation in the aging process and
      lifespan determination. In addition, we discuss the effect of caloric restriction
      on age-associated mitochondrial changes and its role in longevity. Taking these
      findings together, we suggest that decline in mitochondrial energy metabolism,
      enhanced mitochondrial oxidative stress, and accumulation of mtDNA mutations are
      important contributors to human aging.

PMID- 22399427
TI  - Mitochondria in neurodegeneration.
AB  - Many neurodegenerative diseases demonstrate abnormal mitochondrial morphology and
      biochemical dysfunction. Alterations are often systemic rather than brain
      limited. Mitochondrial dysfunction may arise as a consequence of abnormal
      mitochondrial DNA, mutated nuclear proteins that interact directly or indirectly
      with mitochondria, or through unknown causes. In most cases it is unclear where
      mitochondria sit in relation to the overall disease cascades that ultimately
      causes neuronal dysfunction and death, and there is still controversy regarding
      the question of whether mitochondrial dysfunction is a necessary step in
      neurodegeneration. In this chapter we highlight and catalogue mitochondrial
      perturbations in some of the major neurodegenerative diseases including
      Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis
      (ALS), and Huntington's disease (HD). We consider data that suggest mitochondria
      may be critically involved in neurodegenerative disease neurodegeneration
      cascades.

PMID- 22399430
TI  - Mitochondria and drugs.
AB  - Mitochondria play a central role in the life and death of cells. They are not
      merely the centre for energy metabolism, but are also the headquarters for
      different catabolic and anabolic processes, calcium fluxes, and various
      signalling pathways. Mitochondria maintain homeostasis in the cell by interacting
      with reactive oxygen-nitrogen species and responding adequately to different
      stimuli. In this context, the interaction of pharmacological agents with
      mitochondria is an aspect of molecular biology that is too often disregarded, not
      only in terms of toxicology but also from a therapeutic point of view, especially
      considering the potential therapeutic applications related to the modulation of
      mitochondrial activity.At the mitochondrial level, there are several potential
      drug targets that can lead to toxicity, but only for few of them, a real clinical
      counterpart has been demonstrated. Recently, antiviral nucleoside analogues have
      shown mitochondrial toxicity through the inhibition of DNA polymerase-gamma.
      Other drugs targeted to different components of the mitochondrial channels can
      disrupt ion homeostasis or affect the mitochondrial permeability transition pore.
      Many molecules are known inhibitors of the mitochondrial electron transport
      chain, interfering with one or more of the complexes in the respiratory chain.
      Some drugs, including non-steroidal anti-inflammatory drugs (NSAIDs), may lead to
      uncoupling of oxidative phosphorylation, while the mitochondrial toxicity of
      other drugs seems to depend on the production of free radicals, although this
      mechanism has yet to be defined. Besides toxicity, other drugs have been targeted
      to mitochondria to treat mitochondrial dysfunctions. Many drugs have been
      recently developed to target the mitochondria of cancer cells in order to trigger
      apoptosis or necrosis. The aim of this chapter is to underline the role of
      mitochondria in pharmacology and toxicology, stressing all the potential
      therapeutic approaches being due to iatrogenic modulation of the multitude of
      mitochondrial activities.

PMID- 22399431
TI  - Iatrogenic mitochondriopathies: a recent lesson from nucleoside/nucleotide
      reverse transcriptase inhibitors.
AB  - The use of nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) has
      revolutionized the treatment of infection by human immunodeficiency virus (HIV)
      and hepatitis-B virus. NRTIs can suppress viral replication in the long-term, but
      possess significant toxicity that can seriously compromise treatment
      effectiveness. The major toxicity of NRTIs is mitochondrial toxicity. This
      manifests as serious side effects such as myopathy, peripheral neuropathy and
      lactic acidosis. In general, it is believed that the mitochondrial pathogenesis
      is closely related to the effect of NRTIs on mitochondrial DNA polymerase-gamma.
      Depletion and mutation of mitochondrial DNA during chronic NRTI therapy may lead
      to cellular respiratory dysfunction and release of reactive oxidative species,
      resulting in cellular damage. It is now apparent that the etiology is far more
      complex than originally thought. It appears to involve multiple mechanisms as
      well as host factors such as HIV per se, inborn mitochondrial mutation, and sex.
      Management of mitochondrial toxicity during NRTI therapy remains a challenge.
      Interruption of NRTI therapy and substitution of the causative agents with
      alternative better-tolerated NRTIs represents the mainstay of management for
      mitochondrial toxicity and its clinical manifestations. A range of
      pharmacological approaches has been proposed as treatments and prophylaxes.

PMID- 22399432
TI  - Dysfunction of mitochondrial respiratory chain complex I in neurological
      disorders: genetics and pathogenetic mechanisms.
AB  - This chapter covers genetic and biochemical aspects of mitochondrial
      bioenergetics dysfunction in neurological disorders associated with complex I
      defects. Complex I formation and functionality in mammalian cells depends on
      coordinated expression of nuclear and mitochondrial genes, post-translational
      subunit modifications, mitochondrial import/maturation of nuclear encoded
      subunits, subunits interaction and stepwise assembly, and on proteolytic
      processing. Examples of complex I dysfunction are herein presented: homozygous
      mutations in the nuclear NDUFS1 and NDUFS4 genes for structural components of
      complex I; an autosomic recessive form of encephalopathy associated with enhanced
      proteolytic degradation of complex I; familial cases of Parkinson associated to
      mutations in the PINK1 and Parkin genes, in particular, homoplasmic mutations in
      the ND5 and ND6 mitochondrial genes of the complex I, coexistent with mutation in
      the PINK1 gene. This knowledge, besides clarifying molecular aspects of the
      pathogenesis of hereditary diseases, can also provide hints for understanding the
      involvement of complex I in neurological disorders, as well as for developing
      therapeutical strategies.

PMID- 22399433
TI  - Anthracyclines and mitochondria.
AB  - Anthracyclines remain the cornerstone in the treatment of many malignancies
      including lymphomas, leukaemias, and sarcomas. Unfortunately, the clinical use of
      these potent chemotherapeutics is severely limited by the development of a
      progressive dose-dependent cardiomyopathy that irreversibly evolves toward
      congestive heart failure. The molecular mechanisms responsible for anthracycline
      anticancer activity as well as those underlying anthracycline-induced
      cardiotoxicity are incompletely understood and remain a matter of remarkable
      controversy. Anthracyclines have long been considered to induce cardiotoxicity by
      mechanisms different from those mediating their anticancer activity. In
      particular, anthracycline antitumor efficacy is associated with nuclear DNA
      intercalation, topoisomerase II inhibition and drug-DNA adducts formation,
      whereas the cardiotoxicity is prevalently ascribed to oxidative stress and
      mitochondrial dysfunction. At present, however, the view that distinct mechanisms
      are implied in anticancer and cardiotoxic responses to anthracycline therapy does
      not seem fully convincing since beneficial (anticancer) and detrimental
      (cardiotoxic) effects are to some extent overlapping, share the subcellular
      organelle targets, the molecular effectors and the pathophysiological processes
      (i.e. DNA strand breaks, oxidative stress, signalling pathways, mitochondrial
      dysfunctions, apoptosis etc.).Here, we review the potential role of mitochondria
      in the molecular mechanisms underlying anthracyclines anticancer activity as well
      as in the pathogenesis of anthracycline-induced cardiotoxicity.

PMID- 22399434
TI  - Mitochondrial proteomic approaches for new potential diagnostic and prognostic
      biomarkers in cancer.
AB  - Mitochondrial dysfunction and mutations in mitochondrial DNA have been implicated
      in a wide variety of human diseases, including cancer. In recent years,
      considerable advances in genomic, proteomic and bioinformatic technologies have
      made it possible the analysis of mitochondrial proteome, leading to the
      identification of over 1,000 proteins which have been assigned unambiguously to
      mitochondria. Defining the mitochondrial proteome is a fundamental step for fully
      understanding the organelle functions as well as mechanisms underlying
      mitochondrial pathology. In fact, besides giving information on mitochondrial
      physiology, by characterizing all the components of this subcellular organelle,
      the application of proteomic technologies permitted now to study the proteins
      involved in many crucial properties in cell signaling, cell differentiation and
      cell death and, in particular, to identify mitochondrial proteins that are
      aberrantly expressed in cancer cells. An improved understanding of the
      mitochondrial proteome could be essential to shed light on the connection between
      mitochondrial dysfunction, deregulation of apoptosis and tumorigenesis and to
      discovery new therapeutic targets for mitochondria-related diseases.

PMID- 22399435
TI  - Mitochondria in anthropology and forensic medicine.
AB  - Mitochondria's role in crucial metabolic pathways is probably the first answer
      which comes to our minds for the question: what do these tiny organelles serve
      for? However, specific features of their DNA made them extremely useful also in
      the field of anthropology and forensics. MtDNA analyses became a milestone in the
      complex task of unraveling earliest human migrations. Evidence provided by these
      experiments left no doubts on modern humans origins pointing to Africa being our
      cradle. It also contributed to interpretation of putative ways of our dispersal
      around Asia and Americas thousands years ago. On the other hand, analysis of
      mtDNA is well established and valuable tool in forensic genetics. When other
      definitely more popular markers give no answer on identity, it is the time to
      employ information carried by mitochondria. This chapter summarizes not only
      current reports on the role of mitochondria in forensics and reconstruction of
      modern humans phylogeny, but also calls one's attention to a broad range of
      difficulties and constraints associated with mtDNA analyses.

PMID- 22399436
TI  - The impact of age on the atrial substrate: insights from patients with a low scar
      burden undergoing catheter ablation of persistent atrial fibrillation.
AB  - BACKGROUND: Advancing age is a strong risk factor for the development of atrial
      fibrillation (AF). However, its impact on the left atrial (LA) substrate in
      patients is not well defined. METHODS: Forty-seven patients underwent catheter
      ablation of persistent AF. Bipolar electrograms from the LA were recorded for
      voltage analysis. The AF cycle length was determined by averaging the cycle
      lengths of ten fibrillatory ("f") waves on lead V(1). The mean amplitude of the
      same ten "f" waves was also determined. The ablation strategy consisted of
      pulmonary vein isolation, electrogram guided, and linear ablation. RESULTS: There
      was an inverse relationship between the mean bipolar LA voltage and age (R = 
      0.58; P < 0.0001). There was a direct relationship between AF cycle length and
      age (R = 0.74; P < 0.0001). There was an inverse relationship between amplitude
      of the "f" waves and age (R = -0.62; P < 0.0001). Areas of scar were found in 15
      of the 47 patients (32%). AF cycle length was longer in patients with vs. those
      without scar (183 +/- 20 vs. 151 +/- 15 ms; P < 0.0001). Advancing age was the
      only predictor of LA scar (OR, 1.32; 95% CI, 1.11-1.58; P < 0.01). Forty patients
      (85%) remain arrhythmia-free without antiarrhythmic medications after a mean
      follow-up of 18 +/- 10 months. Neither age nor LA scar was associated with
      outcome. CONCLUSIONS: In patients undergoing ablation of persistent AF, advancing
      age makes for a complex LA substrate that is characterized by areas of low
      voltage/scar, and yet is associated with a lower AF frequency. LA scar did not
      seem to impact outcome in this small study.

PMID- 22399437
TI  - From horse thief to professor: confessions of a plant physiologist.
AB  - Can 50 years of research, performed between ignorance and the wish to know, and
      executed between hope, despair, satisfaction and pain, be compressed into an
      abstract? What has been done in more than 50 years may be expressed in four
      words: it was worth it. If I had another life, I would do it again. In the
      beginning of my career, life was an enigma. It still is. Molecular details of the
      workings of life had been largely unknown when I began. Now, at the end, I still
      wish to know details: how is light, master of life, manipulated to either support
      life, when photosynthesis is possible, or to protect it when light endangers it.
      What is the molecular and the physical nature of the biological mechanisms which
      control both, energy conservation and energy dissipation, in photosynthesis?

PMID- 22399438
TI  - Does carpal tunnel release provide long-term relief in patients with hemodialysis
      associated carpal tunnel syndrome?
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is a common complication in patients
      receiving long-term hemodialysis. In the short-term however, these patients are
      less likely to have pain relief and restoration of function after carpal tunnel
      release. However, it is unclear whether patients who have release for
      hemodialysis-associated CTS have differing persisting relief of symptoms compared
      with patients with idiopathic CTS. QUESTIONS/PURPOSES: We therefore compared (1)
      the severity of pain and level of function in patients who had release for
      hemodialysis-associated CTS with scores of patients who had release for
      idiopathic CTS, and (2) the operation-related complications. METHODS: We
      retrospectively reviewed 36 patients with CTS who were receiving hemodialysis and
      54 patients with idiopathic CTS. Control subjects were matched for age, gender,
      and symptom severity. We obtained Boston Carpal Tunnel Questionnaire (BCTQ)
      scores preoperatively and at each followup. The minimum followup was 24 months
      (mean, 44.3 months; range, 24-90 months), although all comparisons were made at 2
      years. RESULTS: Two years after carpal tunnel release, the mean BCTQ-symptom (S)
      /BCTQ-function (F) scores improved from 3.3/2.1 to 2.1/2.1 in the hemodialysis
      associated CTS group and from 3.2/2.3 to 1.4/1.4 in the idiopathic CTS group. All
      but six patients receiving hemodialysis had lower (better) BCTQ-S scores than
      their initial scores. Four patients had complications, all with hemodialysis
      associated CTS: two had revision carpal tunnel releases and two had delayed wound
      healing. We observed no arteriovenous fistula-related complication. CONCLUSIONS:
      Patients with hemodialysis-associated CTS seem to remain impaired, unlike
      patients with idiopathic CTS, but the majority of them might have much improved
      CTS-related symptoms at 2 years after carpal tunnel release.

PMID- 22399439
TI  - Paediatric dose measurements for chest X-ray examinations at Maternity and
      Children Hospital in Najran - Saudi Arabia.
AB  - The entrance skin dose (ESD) of chest X-ray examinations for AP and PA
      projections of paediatric patients at Maternity and Children Hospital in Najran,
      Saudi Arabia have been obtained using DoseCal software. The majority of the
      results obtained show low measured ESD for chest X-ray examinations. The mean of
      ESD for the AP projection was found to be 37.5, 40.5, 41.3, and 52.3 MU Gy for
      age groups 0-1, >1-5, >5-10, and >10-15 years respectively. However, the ESD for
      PA projection was found to be 50.7 and 56.7 MU Gy for age groups >5-10, and >10
      15 years respectively.

PMID- 22399440
TI  - Incorrect and inconsistent use of trade marks by contributors to APESM.

PMID- 22399441
TI  - Identification of host fruit volatiles from domestic apple (Malus domestica),
      native black hawthorn (Crataegus douglasii) and introduced ornamental hawthorn
      (C. monogyna) attractive to Rhagoletis pomonella flies from the western United
      States.
AB  - The apple maggot fly, Rhagoletis pomonella, infests apple (Malus domestica) and
      hawthorn species (most notably the downy hawthorn, Crataegus mollis) in the
      eastern USA. Evidence suggests that the fly was introduced into the western USA
      sometime in the last 60 years. In addition to apple, R. pomonella also infests
      two species of hawthorns in the western USA as major hosts: the native black
      hawthorn (C. douglasii) and the introduced ornamental English hawthorn, C.
      monogyna. Apple and downy hawthorn-origin flies in the eastern USA use volatile
      blends emitted from the surface of their respective ripening fruit to find and
      discriminate among host trees. To test whether the same is true for western
      flies, we used coupled gas chromatography and electroantennographic detection (GC
      EAD) and developed a 7-component apple fruit blend for western apple-origin
      flies, an 8-component black hawthorn fruit blend for flies infesting C.
      douglasii, and a 9-component ornamental hawthorn blend for flies from C.
      monogyna. Crataegus douglasii and C. monogyna-origin flies showed similar levels
      of upwind directed flight to their respective natal synthetic fruit blends in
      flight tunnel assays compared to whole fruit adsorbent extracts, indicating that
      the blends contain all the behaviorally relevant fruit volatiles to induce
      maximal response levels. The black and ornamental hawthorn blends shared four
      compounds in common including 3-methylbutan-1-ol, which appears to be a key
      volatile for R. pomonella populations in the eastern, southern, and western USA
      that show a preference for fruit from different Crataegus species. However, the
      blends also differed from one another and from domesticated apple in several
      respects that make it possible that western R. pomonella flies behaviorally
      discriminate among fruit volatiles and form ecologically differentiated host
      races, as is the case for eastern apple and hawthorn flies.

PMID- 22399443
TI  - Characteristics and clinical validity of two immunoassays for ProGRP.
AB  - Progastrin-releasing peptide (proGRP) is a promising serum tumor marker for small
      cell lung cancer (SCLC). We have tested assay specificity and performed a
      correlation study between a recently developed time-resolved immunofluorometric
      assay (TR-IFMA) for proGRP and the established Advanced Life Science Institute
      (ALSI) ELISA method. Between-method correlation and comparison of clinical
      performance were studied in 481 individuals, among them, 178 lung cancers, 84
      benign diseases of the lung, and 219 healthy controls. Follow-up time >6 years
      was observed for 89 patients with SCLC. The two assays had quite different
      epitope specificities where the TR-IFMA recognized a considerable smaller proGRP
      fragment than the ALSI ELISA. However, the correlation between the two methods
      for elevated proGRP values (>85 ng/l) was good (rho = 0.948). Both assays
      displayed good discrimination between benign lung diseases and SCLC. The cut-off
      values for positive classification of SCLC versus non-small cell lung cancers and
      benign lung diseases at >95% specificity were 85 ng/l for the TR-IFMA and 42 ng/l
      for the ALSI ELISA. Both proGRP assays showed good clinical validity. However,
      due to differences in the recommended cut-off values, switching methods is not
      recommended. There was a significant difference in survival of patients with TR
      IFMA proGRP values over the cut-off (85 ng/l) compared with patients with values
      under the cut-off, p = 0.0002. In contrast, the ALSI ELISA assay failed to
      provide statistically significant prognostic information, p = 0.066.

PMID- 22399445
TI  - In vitro cultures of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine)
      -a potential biotechnological rich source of therapeutically important phenolic
      acids.
AB  - The contents of free phenolic acids and cinnamic acid were determined using an
      HPLC method in methanolic extracts from biomass of Schisandra chinensis (Turcz.)
      Baill. (Chinese magnolia vine) at different stages of organogenesis, cultured in
      vitro on a few variants of Murashige and Skoog (MS) medium, containing different
      concentrations of plant growth regulators 6-benzylaminopurine (BAP) and 1
      naphthaleneacetic acid (NAA) (from 0.1 to 3.0 mg/l) and in extracts from
      overground parts of plants growing in vivo. Six of 12 analysed compounds were
      detected in all extracts: chlorogenic, p-coumaric, p-hydroxybenzoic,
      protocatechuic, salicylic and syringic acids. Total contents of the examined
      metabolites in biomass of shoot-differentiating callus culture cultivated on six
      MS medium variants were dependent on concentrations of growth regulators in the
      media and ranged from 14.90 to 60.05 mg/100 g d.w. Total contents of the
      compounds in biomass extracts from undifferentiating callus culture maintained
      only on two of six MS medium variants were higher and amounted to 74.54 and 78.24
      mg/100 g d.w. Maximum total contents of phenolic acids in both types of in vitro
      cultures were greater than in fruits (55.73 mg/100 g d.w.) and leaves (4.55
      mg/100 g d.w.) of plants gowning in vivo. Chlorogenic acid and salicylic acid
      were the main compounds identified in biomass extracts of shoot-differentiating
      callus cultures (max 22.60 and 21.17 mg/100 g d.w., respectively), while
      chlorogenic acid (max 38.43 mg/100 g d.w.) and protocatechuic acid (max 20.95
      mg/100 g d.w.) prevailed in the extracts from undifferentiating callus cultures.
      Other compounds dominated in fruits, namely p-coumaric acid (23.36 mg/100 g d.w.)
      and syringic acid (14.96 mg/100 g d.w.). This is the first report on biochemical
      potential of cells from S. chinensis in vitro cultures to produce the
      biologically active phenolic acids. These are the first results on the analysis
      of this group of metabolites in overground parts of plants growing in vivo, too.

PMID- 22399446
TI  - Autism spectrum disorders in Hispanics and non-Hispanics.
AB  - OBJECTIVES: To compare differences in autism between Hispanic and non-Hispanics.
      We also examined the relationship between multiple language exposure and language
      function and scores of children. METHODS: The Childhood Autism Risks from
      Genetics and the Environment (CHARGE) study is an ongoing population-based case
      control study with children sampled (n=1061) from three strata: those with autism
      (AU) or autism spectrum disorder (ASD); developmental delay (DD); or the general
      population (GP). RESULTS: Non-Hispanic cases demonstrated higher cognitive
      composite scores for the Mullen Scales of Early Learning (MSEL). There were
      significant associations between multiple language exposure and MSEL subscales
      for receptive language and expressive language, in both cases (AU/ASD) and TD
      controls, but not DD controls. Results of multivariate regression analyses
      suggest several predictors to be associated with lower Mullen expressive language
      scores including: diagnosis of ASD/AU, speaking to the child in a second language
      25-50% of the time and Hispanic ethnicity; while maternal college education was
      associated with higher scores. CONCLUSION: Overall, the CHARGE Hispanic group
      displayed more similarities than differences compared to non-Hispanics in terms
      of autistic phenotypes and maladaptive & adaptive scores for cases. The
      relationship between multiple language use and cognitive scores warrants a closer
      look.

PMID- 22399447
TI  - Translation and validation of the developmental, dimensional and diagnostic
      interview (3Di) for diagnosis of autism spectrum disorder in Thai children.
AB  - This study aimed to examine the effectiveness of a translated version of the
      short version of the Developmental, Dimensional and Diagnostic Interview (3Di) in
      discriminating children with autism spectrum disorders (ASDs) from typically
      developing children. Two groups, comprising 63 children with clinically
      ascertained ASDs and 67 typically developing children, were interviewed with the
      short 3Di translated version. Mean 3Di scale scores in each domain of autistic
      symptoms (social reciprocity, communication, and repetitive/stereotyped
      behaviors) were significantly higher in the ASD group than in the typically
      developing group. The optimal receiver operating characteristics curve cut-off
      scores were found to be 10, 8, and 3 for social reciprocity domain, communication
      domain, and repetitive/stereotyped behaviors domain, respectively, which are
      identical to the original English standardization. Corresponding sensitivities
      and specificities were 76.2% and 80.9% for the social reciprocity domain; 85.7%
      and 73.5% for the communication domain; and 66.7% and 80.9% for the repetitive
      behaviors domain. The areas under the curve were 0.89 (95% CI = 0.84-0.94), 0.88
      (95% CI = 0.82-0.94), and 0.79 (95% CI = 0.71-0.87), respectively. The short 3Di
      Thai version is found to be a useful diagnostic instrument for differentiating
      between clinically diagnosed children with ASDs and typically developing
      children, although further replication is needed.

PMID- 22399444
TI  - Ubiquitination and the Ubiquitin-Proteasome System as regulators of transcription
      and transcription factors in epithelial mesenchymal transition of cancer.
AB  - Epithelial to Mesenchymal Transition (EMT) in cancer is a process that allows
      cancer cells to detach from neighboring cells, become mobile and metastasize and
      shares many signaling pathways with development. Several molecular mechanisms
      which regulate oncogenic properties in neoplastic cells such as proliferation,
      resistance to apoptosis and angiogenesis through transcription factors or other
      mediators are also regulators of EMT. These pathways and downstream transcription
      factors are, in their turn, regulated by ubiquitination and the Ubiquitin
      Proteasome System (UPS). Ubiquitination, the covalent link of the small 76-amino
      acid protein ubiquitin to target proteins, serves as a signal for protein
      degradation by the proteasome or for other outcomes such as endocytosis,
      degradation by the lysosome or directing these proteins to specific cellular
      compartments. This review discusses aspects of the regulation of EMT by
      ubiquitination and the UPS and underlines its complexity focusing on
      transcription and transcription factors regulating EMT and are being regulated by
      ubiquitination.

PMID- 22399448
TI  - Compliance with requests by children with autism: the impact of sentence type.
AB  - This study assesses the extent to which children with autism understand requests
      performed with grammatically non-imperative sentence types. Ten children with
      autism were videotaped in naturalistic conditions. Four grammatical sentence
      types were distinguished: imperative, declarative, interrogative and sub
      sentential. For each category, the proportion of requests complied with
      significantly exceeded the proportion of requests not complied with, and no
      difference across categories was found. These results show that children with
      autism do not rely exclusively on the linguistic form to interpret an utterance
      as a request.

PMID- 22399449
TI  - A nationwide survey on quality of life and associated factors of adults with high
      functioning autism spectrum disorders.
AB  - The psychosocial outcomes of individuals with high-functioning autism spectrum
      disorder (HFASD) appear to be diverse and are often poor relative to their
      intellectual or language level. To identify predictive variables that are
      potentially ameliorable by therapeutic intervention, this study investigated self
      reported psychosocial quality of life and associated factors for adults with
      HFASD. All participants (n = 154) had a diagnosis of autism spectrum disorder,
      were over 18 years of age, lived in the community, and had used one or more
      support services during the survey period. The results demonstrated that
      psychosocial quality of life was lower than that of the general Japanese adult
      population. Environmental factors, such as mother's support and early diagnosis,
      were associated with better quality of life, and aggressive behaviors were
      associated with poorer quality of life, while expressive language level at
      preschool years, a conventional outcome predictor, did not predict quality of
      life. These results emphasize that quality of life measures should be included as
      outcome indicators in treating individuals with HFASD.

PMID- 22399450
TI  - A continuous false belief task reveals egocentric biases in children and
      adolescents with autism spectrum disorders.
AB  - This study reports on a new false belief measure in a sample of 124 children and
      adolescents with or without high functioning autism (HFASD). In the classic
      paradigm, a participant predicts in which of two discrete locations a deceived
      protagonist will look for an object. In the current Sandbox task, the object is
      buried and reburied in a sandbox, thus creating a continuum between locations.
      Compared to typically developing individuals (n=62), those with HFASD (n=62)
      showed a larger egocentric bias on the Sandbox task. They failed to take the
      protagonist's false belief into account, despite their adequate ability to infer
      advanced mental states. This indicates that sensitive measures can reveal subtle
      first order Theory of Mind impairments in HFASD individuals.

PMID- 22399452
TI  - Toddler autism screening questionnaire: development and potential clinical
      validity.
AB  - No feasible screening instrument is available for early detection of children
      with autism in Taiwan. The existing instruments may not be appropriate for use in
      Taiwan due to different health care systems and child-rearing cultures. The
      purpose of this study was to develop and test a screening questionnaire for
      generic autism. The initial 18-item screening questionnaire was developed by a
      child psychiatrist using face-to-face interviews with 10 families of children
      with autism and then tested on a sample of families of 18 children with autism
      and of 59 typically developing children. Of these 18 items, 15 had fair or better
      item discrimination (kappa >0.20) and were selected for the revised screening
      questionnaire. In the revised questionnaire, cutoff scores of 5 and 6 offered
      100% sensitivity and 96.5% specificity, with the area under the receiver
      operating characteristic curve of 0.983. The revised screening instrument has
      high sensitivity and specificity, making it potentially useful for screening
      Taiwanese children at risk for autism. This instrument should be further tested
      in a population-based study.

PMID- 22399453
TI  - Tangled trees: the challenge of inferring species trees from coalescent and
      noncoalescent genes.
AB  - Phylogenies based on different genes can produce conflicting phylogenies; methods
      that resolve such ambiguities are becoming more popular, and offer a number of
      advantages for phylogenetic analysis. We review so-called species tree methods
      and the biological forces that can undermine them by violating important aspects
      of the underlying models. Such forces include horizontal gene transfer, gene
      duplication, and natural selection. We review ways of detecting loci influenced
      by such forces and offer suggestions for identifying or accommodating them. The
      way forward involves identifying outlier loci, as is done in population genetic
      analysis of neutral and selected loci, and removing them from further analysis,
      or developing more complex species tree models that can accommodate such loci.

PMID- 22399451
TI  - The rubber hand illusion in children with autism spectrum disorders: delayed
      influence of combined tactile and visual input on proprioception.
AB  - In the rubber hand illusion, perceived hand ownership can be transferred to a
      rubber hand after synchronous visual and tactile stimulation. Perceived body
      ownership and self-other relation are foundational for development of self
      awareness, imitation, and empathy, which are all affected in autism spectrum
      disorders (ASD). We examined the rubber hand illusion in children with and
      without ASD. Children with ASD were initially less susceptible to the illusion
      than the comparison group, yet showed the effects of the illusion after 6
      minutes. Delayed susceptibility to the illusion may result from atypical
      multisensory temporal integration and/or an unusually strong reliance on
      proprioception. Children with ASD who displayed less empathy were significantly
      less likely to experience the illusion than those with more intact ability to
      express empathy. A better understanding of body representation in ASD may
      elucidate neural underpinnings of social deficits, thus informing future
      intervention approaches.

PMID- 22399454
TI  - Modeling gene family evolution and reconciling phylogenetic discord.
AB  - Large-scale databases are available that contain homologous gene families
      constructed from hundreds of complete genome sequences from across the three
      domains of life. Here, we discuss the approaches of increasing complexity aimed
      at extracting information on the pattern and process of gene family evolution
      from such datasets. In particular, we consider the models that invoke processes
      of gene birth (duplication and transfer) and death (loss) to explain the
      evolution of gene families. First, we review birth-and-death models of family
      size evolution and their implications in light of the universal features of
      family size distribution observed across different species and the three domains
      of life. Subsequently, we proceed to recent developments on models capable of
      more completely considering information in the sequences of homologous gene
      families through the probabilistic reconciliation of the phylogenetic histories
      of individual genes with the phylogenetic history of the genomes in which they
      have resided. To illustrate the methods and results presented, we use data from
      the HOGENOM database, demonstrating that the distribution of homologous gene
      family sizes in the genomes of the eukaryota, archaea, and bacteria exhibits
      remarkably similar shapes. We show that these distributions are best described by
      models of gene family size evolution, where for individual genes the death (loss)
      rate is larger than the birth (duplication and transfer) rate but new families
      are continually supplied to the genome by a process of origination. Finally, we
      use probabilistic reconciliation methods to take into consideration additional
      information from gene phylogenies, and find that, for prokaryotes, the majority
      of birth events are the result of transfer.

PMID- 22399456
TI  - Philosophy and evolution: minding the gap between evolutionary patterns and tree
      like patterns.
AB  - Ever since Darwin, the familiar genealogical pattern known as the Tree of Life
      (TOL) has been prominent in evolutionary thinking and has dominated not only
      systematics, but also the analysis of the units of evolution. However, recent
      findings indicate that the evolution of DNA, especially in prokaryotes and such
      DNA vehicles as viruses and plasmids, does not follow a unique tree-like pattern.
      Because evolutionary patterns track a greater range of processes than those
      captured in genealogies, genealogical patterns are in fact only a subset of a
      broader set of evolutionary patterns. This fact suggests that evolutionists who
      focus exclusively on genealogical patterns are blocked from providing a
      significant range of genuine evolutionary explanations. Consequently, we
      highlight challenges to tree-based approaches, and point the way toward more
      appropriate methods to study evolution (although we do not present them in
      technical detail). We argue that there is significant benefit in adopting wider
      range of models, evolutionary representations, and evolutionary explanations,
      based on an analysis of the full range of evolutionary processes. We introduce an
      ecosystem orientation into evolutionary thinking that highlights the importance
      of "type 1 coalitions" (functionally related units with genetic exchanges, aka
      "friends with genetic benefits"), "type 2 coalitions" (functionally related units
      without genetic exchanges), "communal interactions," and "emergent evolutionary
      properties." On this basis, we seek to promote the study of (especially
      prokaryotic) evolution with dynamic evolutionary networks, which are less
      constrained than the TOL, and to provide new ways to analyze an expanded range of
      evolutionary units (genetic modules, recombined genes, plasmids, phages and
      prokaryotic genomes, pangenomes, microbial communities) and evolutionary
      processes. Finally, we discuss some of the conceptual and practical questions
      raised by such network-based representation.

PMID- 22399455
TI  - Genome-wide comparative analysis of phylogenetic trees: the prokaryotic forest of
      life.
AB  - Genome-wide comparison of phylogenetic trees is becoming an increasingly common
      approach in evolutionary genomics, and a variety of approaches for such
      comparison have been developed. In this article, we present several methods for
      comparative analysis of large numbers of phylogenetic trees. To compare
      phylogenetic trees taking into account the bootstrap support for each internal
      branch, the Boot-Split Distance (BSD) method is introduced as an extension of the
      previously developed Split Distance method for tree comparison. The BSD method
      implements the straightforward idea that comparison of phylogenetic trees can be
      made more robust by treating tree splits differentially depending on the
      bootstrap support. Approaches are also introduced for detecting tree-like and net
      like evolutionary trends in the phylogenetic Forest of Life (FOL), i.e., the
      entirety of the phylogenetic trees for conserved genes of prokaryotes. The
      principal method employed for this purpose includes mapping quartets of species
      onto trees to calculate the support of each quartet topology and so to quantify
      the tree and net contributions to the distances between species. We describe the
      application of these methods to analyze the FOL and the results obtained with
      these methods. These results support the concept of the Tree of Life (TOL) as a
      central evolutionary trend in the FOL as opposed to the traditional view of the
      TOL as a "species tree."

PMID- 22399457
TI  - Selection on the protein-coding genome.
AB  - Populations evolve as mutations arise in individual organisms and, through
      hereditary transmission, may become "fixed" (shared by all individuals) in the
      population. Most mutations are lethal or have negative fitness consequences for
      the organism. Others have essentially no effect on organismal fitness and can
      become fixed through the neutral stochastic process known as random drift.
      However, mutations may also produce a selective advantage that boosts their
      chances of reaching fixation. Regions of genes where new mutations are
      beneficial, rather than neutral or deleterious, tend to evolve more rapidly due
      to positive selection. Genes involved in immunity and defense are a well-known
      example; rapid evolution in these genes presumably occurs because new mutations
      help organisms to prevail in evolutionary "arms races" with pathogens. In recent
      years, genome-wide scans for selection have enlarged our understanding of the
      evolution of the protein-coding regions of the various species. In this chapter,
      we focus on the methods to detect selection in protein-coding genes. In
      particular, we discuss probabilistic models and how they have changed with the
      advent of new genome-wide data now available.

PMID- 22399459
TI  - The origin and evolution of new genes.
AB  - New genes are a major source of genetic innovation in genomes. However, until
      recently, understanding how new genes originate and how they evolve was hampered
      by the lack of appropriate genetic datasets. The advent of the genomic era
      brought about a revolution in the amount of data available to study new genes.
      For the first time, decades-old theoretical principles could be tested
      empirically and novel and unexpected avenues of research opened up. This chapter
      explores how genomic data can and is being used to study both the origin and
      evolution of new genes and the surprising discoveries made thus far.

PMID- 22399458
TI  - Methods to detect selection on noncoding DNA.
AB  - Vast tracts of noncoding DNA contain elements that regulate gene expression in
      higher eukaryotes. Describing these regulatory elements and understanding how
      they evolve represent major challenges for biologists. Advances in the ability to
      survey genome-scale DNA sequence data are providing unprecedented opportunities
      to use evolutionary models and computational tools to identify functionally
      important elements and the mode of selection acting on them in multiple species.
      This chapter reviews some of the current methods that have been developed and
      applied on noncoding DNA, what they have shown us, and how they are limited.
      Results of several recent studies reveal that a significantly larger fraction of
      noncoding DNA in eukaryotic organisms is likely to be functional than previously
      believed, implying that the functional annotation of most noncoding DNA in these
      organisms is largely incomplete. In Drosophila, recent studies have further
      suggested that a large fraction of noncoding DNA divergence observed between
      species may be the product of recurrent adaptive substitution. Similar studies in
      humans have revealed a more complex pattern, with signatures of recurrent
      positive selection being largely concentrated in conserved noncoding DNA
      elements. Understanding these patterns and the extent to which they generalize to
      other organisms awaits the analysis of forthcoming genome-scale polymorphism and
      divergence data from more species.

PMID- 22399460
TI  - Evolution of protein domain architectures.
AB  - This chapter reviews the current research on how protein domain architectures
      evolve. We begin by summarizing work on the phylogenetic distribution of
      proteins, as this directly impacts which domain architectures can be formed in
      different species. Studies relating domain family size to occurrence have shown
      that they generally follow power law distributions, both within genomes and
      larger evolutionary groups. These findings were subsequently extended to
      multidomain architectures. Genome evolution models that have been suggested to
      explain the shape of these distributions are reviewed, as well as evidence for
      selective pressure to expand certain domain families more than others. Each
      domain has an intrinsic combinatorial propensity, and the effects of this have
      been studied using measures of domain versatility or promiscuity. Next, we study
      the principles of protein domain architecture evolution and how these have been
      inferred from distributions of extant domain arrangements. Following this, we
      review inferences of ancestral domain architecture and the conclusions concerning
      domain architecture evolution mechanisms that can be drawn from these. Finally,
      we examine whether all known cases of a given domain architecture can be assumed
      to have a single common origin (monophyly) or have evolved convergently
      (polyphyly).

PMID- 22399461
TI  - Estimating recombination rates from genetic variation in humans.
AB  - Recombination acts to shuffle the existing genetic variation within a population,
      leading to various approaches for detecting its action and estimating the rate at
      which it occurs. Here, we discuss the principal methodological and analytical
      approaches taken to understanding the distribution of recombination across the
      human genome. We first discuss the detection of recent crossover events in both
      well-characterised pedigrees and larger populations with extensive recent shared
      ancestry. We then describe approaches for learning about the fine-scale structure
      of recombination rate variation from patterns of genetic variation in unrelated
      individuals. Finally, we show how related approaches using individuals of admixed
      ancestry can provide an alternative approach to analysing recombination.
      Approaches differ not only in the statistical methods used, but also in the
      resolution of inference, the timescale over which recombination events are
      detected, and the extent to which inter-individual variation can be identified.

PMID- 22399462
TI  - Evolution of viral genomes: interplay between selection, recombination, and other
      forces.
AB  - RNA viruses evolve very rapidly, often recombine, and are subject to strong host
      (immune response) and anthropogenic (antiretroviral drugs) selective forces.
      Given their compact and extensively sequenced genomes, comparative analysis of
      RNA viral data can provide important insights into the molecular mechanisms of
      adaptation, pathogenicity, immune evasion, and drug resistance. In this chapter,
      we present an example-based overview of recent advances in evolutionary models
      and statistical approaches that enable screening viral alignments for evidence of
      adaptive change in the presence of recombination, detecting bursts of directional
      adaptive evolution associated with the phenotypic changes, and detecting of
      coevolving sites in viral genes.

PMID- 22399463
TI  - Association mapping and disease: evolutionary perspectives.
AB  - In this chapter, we give a short introduction to the genetics of complex disease
      with special emphasis on evolutionary models for disease genes and the effect of
      different models on the genetic architecture, and finally give a survey of the
      state-of-the-art of genome-wide association studies.

PMID- 22399464
TI  - Ancestral population genomics.
AB  - The full genomes of several closely related species are now available, opening an
      emerging field of investigation borrowing both from population genetics and
      phylogenetics. Providing we can properly model sequence evolution within
      populations undergoing speciation events, this resource enables us to estimate
      key population genetics parameters, such as ancestral population sizes and split
      times. Furthermore, we can enhance our understanding of the recombination process
      and investigate various selective forces. We discuss the basic speciation models
      for closely related species, including the isolation and isolation-with-migration
      models. A major point in our discussion is that only a few complete genomes
      contain much information about the whole population. The reason being that
      recombination unlinks genomic regions, and therefore a few genomes contain many
      segments with distinct histories. The challenge of population genomics is to
      decode this mosaic of histories in order to infer scenarios of demography and
      selection. We survey different approaches for understanding ancestral species
      from analyses of genomic data from closely related species. In particular, we
      emphasize core assumptions and working hypothesis. Finally, we discuss
      computational and statistical challenges that arise in the analysis of population
      genomics data sets.

PMID- 22399465
TI  - Nonredundant representation of ancestral recombinations graphs.
AB  - The network structure that captures the common evolutionary history of a diploid
      population has been termed an ancestral recombinations graph. When the structure
      is a tree the number of internal nodes is usually [Formula: see text] where K is
      the number of samples. However, when the structure is not a tree, this number has
      been observed to be very large. We explore the possible redundancies in this
      structure. This has implications both in simulations and in reconstructability
      studies.

PMID- 22399466
TI  - Using genomic tools to study regulatory evolution.
AB  - Differences in gene regulation are thought to play an important role in
      speciation and adaptation. Comparative genomic studies of gene expression levels
      have identified a large number of differentially expressed genes among species,
      and, in a number of cases, also pointed to connections between interspecies
      differences in gene regulation and differences in ultimate physiological or
      morphological phenotypes. The mechanisms underlying changes in gene regulation
      are also being actively studied using comparative genomic approaches. However,
      the relative importance of different regulatory mechanisms to interspecies
      differences in gene expression levels is not yet well understood. In particular,
      it is often difficult to infer causality between apparent differences in
      regulatory mechanisms and changes in gene expression levels, a challenge that is
      compounded by the fact that the link between sequence variation and gene
      regulation is not clear. Indeed, in certain cases, gene regulation can be
      conserved even when sequences at associated regulatory elements have changed. In
      this chapter, I examine different genomic approaches to the study of regulatory
      evolution and the underlying genetic and epigenetic regulatory mechanisms. I try
      to distinguish between hypothesis-driven and exploratory studies, and argue that
      the latter class of studies provides valuable information in its own right as
      well as necessary context for the former. I discuss issues related to study
      designs and statistical analyses of genomic studies, and review the evidence for
      natural selection on gene expression levels and associated regulatory mechanisms.
      Most of the issues that are discussed pertain to the general nature of
      multivariate genomic data, and thus are often relevant regardless of the
      technology that is used to collect high-throughput genomic data (for example,
      microarrays or massively parallel sequencing).

PMID- 22399467
TI  - Characterization and evolutionary analysis of protein-protein interaction
      networks.
AB  - While researchers have known the importance of the protein-protein interaction
      for decades, recent innovations in large-scale screening techniques have caused a
      shift in the paradigm of protein function analysis. Where the focus was once on
      the individual protein, attention is now directed to the surrounding network of
      protein associations. As protein interaction networks can provide useful insights
      into the potential function of and phenotypes associated with proteins, the
      increasing availability of large-scale protein interaction data suggests that
      molecular biologists can extract more meaningful hypotheses through examination
      of these large networks. Further, increasing availability of high-quality protein
      interaction data in multiple species has allowed interpretation of the properties
      of networks (i.e., the presence of hubs and modularity) from an evolutionary
      perspective. In this chapter, we discuss major previous findings derived from
      analyses of large-scale protein interaction data, focusing on approaches taken by
      landmark assays in evaluating the structure and evolution of these networks. We
      then outline basic techniques for protein interaction network analysis with the
      goal of pointing out the benefits and potential limitations of these approaches.
      As the majority of large-scale protein interaction data has been generated in
      budding yeast, literature described here focuses on this important model organism
      with references to other species included where possible.

PMID- 22399468
TI  - Statistical methods in metabolomics.
AB  - Metabolomics is the relatively new field in bioinformatics that uses measurements
      on metabolite abundance as a tool for disease diagnosis and other medical
      purposes. Although closely related to proteomics, the statistical analysis is
      potentially simpler since biochemists have significantly more domain knowledge
      about metabolites. This chapter reviews the challenges that metabolomics poses in
      the areas of quality control, statistical metrology, and data mining.

PMID- 22399469
TI  - Introduction to the analysis of environmental sequences: metagenomics with MEGAN.
AB  - Metagenomics is the study of microbial organisms using sequencing applied
      directly to environmental samples. Similarly, in metatranscriptomics and
      metaproteomics, the RNA and protein sequences of such samples are studied. The
      analysis of these kinds of data often starts by asking the questions of "who is
      out there?", "what are they doing?", and "how do they compare?". In this chapter,
      we describe how these computational questions can be addressed using MEGAN, the
      MEtaGenome ANalyzer program. We first show how to analyze the taxonomic and
      functional content of a single dataset and then show how such analyses can be
      performed in a comparative fashion. We demonstrate how to compare different
      datasets using ecological indices and other distance measures. The discussion is
      conducted using a number of published marine datasets comprising metagenomic,
      metatranscriptomic, metaproteomic, and 16S rRNA data.

PMID- 22399470
TI  - Analyzing epigenome data in context of genome evolution and human diseases.
AB  - This chapter describes bioinformatic tools for analyzing epigenome differences
      between species and in diseased versus normal cells. We illustrate the interplay
      of several Web-based tools in a case study of CpG island evolution between human
      and mouse. Starting from a list of orthologous genes, we use the Galaxy Web
      service to obtain gene coordinates for both species. These data are further
      analyzed in EpiGRAPH, a Web-based tool that identifies statistically significant
      epigenetic differences between genome region sets. Finally, we outline how the
      use of the statistical programming language R enables deeper insights into the
      epigenetics of human diseases, which are difficult to obtain without writing
      custom scripts. In summary, our tutorial describes how Web-based tools provide an
      easy entry into epigenome data analysis while also highlighting the benefits of
      learning a scripting language in order to unlock the vast potential of public
      epigenome datasets.

PMID- 22399471
TI  - Genetical genomics for evolutionary studies.
AB  - Genetical genomics combines acquired high-throughput genomic data with genetic
      analysis. In this chapter, we discuss the application of genetical genomics for
      evolutionary studies, where new high-throughput molecular technologies are
      combined with mapping quantitative trait loci (QTL) on the genome in segregating
      populations.The recent explosion of high-throughput data--measuring thousands of
      proteins and metabolites, deep sequencing, chromatin, and methyl-DNA
      immunoprecipitation--allows the study of the genetic variation underlying
      quantitative phenotypes, together termed xQTL. At the same time, mining
      information is not getting easier. To deal with the sheer amount of information,
      powerful statistical tools are needed to analyze multidimensional relationships.
      In the context of evolutionary computational biology, a well-designed experiment
      may help dissect a complex evolutionary trait using proven statistical methods
      for associating phenotypical variation with genomic locations.Evolutionary
      expression QTL (eQTL) studies of the last years focus on gene expression
      adaptations, mapping the gene expression landscape, and, tentatively, eQTL
      networks. Here, we discuss the possibility of introducing an evolutionary prior,
      in the form of gene families displaying evidence of positive selection, and using
      that in the context of an eQTL experiment for elucidating host-pathogen protein
      protein interactions. Through the example of an experimental design, we discuss
      the choice of xQTL platform, analysis methods, and scope of results. The
      resulting eQTL can be matched, resulting in putative interacting genes and their
      regulators. In addition, a prior may help distinguish QTL causality from
      reactivity, or independence of traits, by creating QTL networks.

PMID- 22399472
TI  - Genomics data resources: frameworks and standards.
AB  - The emergence of genomics tools for the evolutionary and comparative biology
      community led to a rapid explosion in the number of online resources targeted at
      this specialized community, including Web-based comparative genomics software,
      such as the Artemis Comparison Tool (WebACT); databases, such as PaleoDB, Global
      Biodiversity Information Facility, and TreeBase; and knowledge frameworks, such
      as the Evolution Ontology. Unfortunately, these providers are largely independent
      of one another and therefore the individual resources do not share any
      centralized plan for how the data or tools would or should be provided. As a
      result, there are a myriad of often incompatible technologies and frameworks
      being used by this community of providers. In this chapter, we explore approaches
      to online resource publication, both those already in use by the community, as
      well as new and emergent frameworks and standards. Exploration of the strengths
      and weaknesses of each approach, together with a brief exploration of the
      philosophy or informatics theory behind the varying approaches, will hopefully
      help readers as they navigate this data space. The discussion is constructed such
      that it lays the groundwork for exploration of a new global standard for data and
      knowledge representation--"The Semantic Web"--that holds promise of providing
      solutions to many of the complexities users face in their attempts to discover
      and integrate biodiversity data, and examples are provided.

PMID- 22399473
TI  - Sharing programming resources between Bio* projects through remote procedure call
      and native call stack strategies.
AB  - Open-source software (OSS) encourages computer programmers to reuse software
      components written by others. In evolutionary bioinformatics, OSS comes in a
      broad range of programming languages, including C/C++, Perl, Python, Ruby, Java,
      and R. To avoid writing the same functionality multiple times for different
      languages, it is possible to share components by bridging computer languages and
      Bio* projects, such as BioPerl, Biopython, BioRuby, BioJava, and R/Bioconductor.
      In this chapter, we compare the two principal approaches for sharing software
      between different programming languages: either by remote procedure call (RPC) or
      by sharing a local call stack. RPC provides a language-independent protocol over
      a network interface; examples are RSOAP and Rserve. The local call stack provides
      a between-language mapping not over the network interface, but directly in
      computer memory; examples are R bindings, RPy, and languages sharing the Java
      Virtual Machine stack. This functionality provides strategies for sharing of
      software between Bio* projects, which can be exploited more often. Here, we
      present cross-language examples for sequence translation, and measure throughput
      of the different options. We compare calling into R through native R, RSOAP,
      Rserve, and RPy interfaces, with the performance of native BioPerl, Biopython,
      BioJava, and BioRuby implementations, and with call stack bindings to BioJava and
      the European Molecular Biology Open Software Suite. In general, call stack
      approaches outperform native Bio* implementations and these, in turn, outperform
      RPC-based approaches. To test and compare strategies, we provide a downloadable
      BioNode image with all examples, tools, and libraries included. The BioNode image
      can be run on VirtualBox-supported operating systems, including Windows, OSX, and
      Linux.

PMID- 22399474
TI  - Scalable computing for evolutionary genomics.
AB  - Genomic data analysis in evolutionary biology is becoming so computationally
      intensive that analysis of multiple hypotheses and scenarios takes too long on a
      single desktop computer. In this chapter, we discuss techniques for scaling
      computations through parallelization of calculations, after giving a quick
      overview of advanced programming techniques. Unfortunately, parallel programming
      is difficult and requires special software design. The alternative, especially
      attractive for legacy software, is to introduce poor man's parallelization by
      running whole programs in parallel as separate processes, using job schedulers.
      Such pipelines are often deployed on bioinformatics computer clusters. Recent
      advances in PC virtualization have made it possible to run a full computer
      operating system, with all of its installed software, on top of another operating
      system, inside a "box," or virtual machine (VM). Such a VM can flexibly be
      deployed on multiple computers, in a local network, e.g., on existing desktop
      PCs, and even in the Cloud, to create a "virtual" computer cluster. Many
      bioinformatics applications in evolutionary biology can be run in parallel,
      running processes in one or more VMs. Here, we show how a ready-made
      bioinformatics VM image, named BioNode, effectively creates a computing cluster,
      and pipeline, in a few steps. This allows researchers to scale-up computations
      from their desktop, using available hardware, anytime it is required. BioNode is
      based on Debian Linux and can run on networked PCs and in the Cloud. Over 200
      bioinformatics and statistical software packages, of interest to evolutionary
      biology, are included, such as PAML, Muscle, MAFFT, MrBayes, and BLAST. Most of
      these software packages are maintained through the Debian Med project. In
      addition, BioNode contains convenient configuration scripts for parallelizing
      bioinformatics software. Where Debian Med encourages packaging free and open
      source bioinformatics software through one central project, BioNode encourages
      creating free and open source VM images, for multiple targets, through one
      central project. BioNode can be deployed on Windows, OSX, Linux, and in the
      Cloud. Next to the downloadable BioNode images, we provide tutorials online,
      which empower bioinformaticians to install and run BioNode in different
      environments, as well as information for future initiatives, on creating and
      building such images.

PMID- 22399476
TI  - The importance of being comprehensive.

PMID- 22399477
TI  - Digital retinal imaging in a residency-based patient-centered medical home.
AB  - BACKGROUND AND OBJECTIVES: Diabetic retinopathy is the leading cause of blindness
      in adults in the United States, and early screening/treatment may preserve
      vision. This study examined the feasibility of using non-mydriatic digital
      retinal imaging (DRI) for retinopathy screening in a busy family medicine
      residency program at the point of care using a nurse-driven protocol. METHODS: We
      compared the number of diabetics screened during a 1-year period before and after
      DRI protocol implementation. We also determined the prevalence of retinopathy,
      assessed patient satisfaction with the alternative screening process, and tracked
      ophthalmologic appointment compliance for patients referred because of abnormal
      screening results. RESULTS: Screening approximately doubled from 161
      patients/year before the protocol to 330 patients/year after protocol
      implementation. However, DRI screening had no impact on ophthalmologic
      appointment compliance; only 58% of 153 patients referred for ophthalmologic
      evaluation because of positive screening findings completed their referral
      appointment. Seven cases needing urgent ophthalmologic treatment were identified.
      Satisfaction with primary care retinopathy screening was high. CONCLUSIONS: Use
      of a nurse-driven protocol for digital retinal imaging at the point of care
      dramatically improves rates of annual retinopathy screening in academic family
      medicine practice and can identify patients who require subspecialty referral.
      However, DRI screening does not improve visit compliance rates with
      ophthalmologists for evaluation and management.

PMID- 22399478
TI  - Quality of colonoscopy services for physicians in the Iowa research network.
AB  - BACKGROUND AND OBJECTIVES: Primary care physicians initiate colorectal cencer
      (CRC) screening and manage health care issues that present from these procedures.
      Quality of colonoscopy services can be determined by a set of indicators. The
      purpose of this study was to identify the quality of colonoscopy services
      provided for patients of family physicians in the Iowa Research Network (IRENE).
      Quality of services was delineated by (1) presence of a colonoscopy report on the
      medical record, if the medical record indicated a colonoscopy had been completed,
      (2) cecal intubation rate, (3) adenoma detection rate, and (4) the content of the
      colonoscopy report. METHODS: Medical record review was conducted in 14 IRENE
      offices. RESULTS: Of 581 medical records indicating a colonoscopy had been
      completed, 89 (15%) did not have a colonoscopy report. The main reasons for
      having the colonoscopy were screening and obvious blood in the stool. Polyp
      detection rate for all colonoscopies was 35%, and the adenoma detction rate for
      screening colonoscopis for men was 31% and for women was 19%. Depth of insertion
      to the cecum was reached for 92%. Items least mentioned in the report were the
      time to complete the procedure and current medications. Only 223 (45%) reports
      listed the follow-up interval for next colonoscopy. Quality of colonoscopy
      services for this group of IRENE physicians was comparable to recommended
      standards of depth of insertion and adenoma detection rate. Improvements are
      warranted to have all colonoscopy reports and follow-up interval of next
      colonoscopy on a patient's medical record.

PMID- 22399479
TI  - Endoscopy training in primary care: innovative training program to increase
      access to endoscopy in primary care.
AB  - BACKGROUND AND OBJECTIVES: Colorectal cancer (CRC) is a significant source of
      morbidity and mortality in the United States. Colonoscopy can be an extension of
      the care provided by a family physician to help substantially reduce CRC
      morbidity and mortality. Family physicians trained in colonoscopy can provide
      access to care in rural and medically underserved areas. METHODS: The Department
      of Family Medicine and the Colorado Area Health Education Center (AHEC) developed
      the Endoscopy Training for Primary Care (ETPC) program to teach primary care
      physicians to perform colonoscopy. The program included online didactic
      education, a formal endoscopy simulator experience, and proctoring by a current
      endoscopist. Participants completed a baseline and follow-up survey assessing CRC
      screening knowledge and the effectiveness of the endoscopy training for ongoing
      screening activities. RESULTS: To date, 94 practitioners and health professional
      students have participated in the study. Ninety-one (97%) completed the online
      didactic portion of the training. Sixty-five participants (77%) were physicians
      or medical students, and the majority (64%) was in the field of family medicine.
      The year 4 (2011) follow-up cohort was comprised of 62% respondents working in an
      urban background and 26% in rural communities. Many participants remain in a
      queue for proctoring by a trained endoscopist. Several participants are
      successfully performing a significant number of colonoscopies. CONCLUSIONS: ETPC
      program showed success in recruiting a large number of physicians and students to
      participate in training. The program enhanced perceptions about the value of
      colon cancer screening and providing screening endoscopy in primary care
      practice. Providing sites for simulation training throughout Colorado provided
      opportunity for providers in rural regions to participate. As a result of this
      training, thousands of patients underwent testing to prevent colon cancer. Future
      research relating to colonoscopy training by family physicians should focus on
      quality assurance and determining best methods for procedural competence.

PMID- 22399480
TI  - Experiences of family medicine residents in primary care obstetrics training.
AB  - BACKGROUND AND OBJECTIVES: Obstetrical practice by family physicians has been
      declining rapidly for many reasons over the past number of decades. One reason
      for this trend is family medicine residents not considering intrapartum care as
      part of their future careers. Decisions such as this may be related to
      experiences during obstetrical training. This study explored the experiences of
      family medicine residents in core primary care obstetrics training. METHODS:
      Using qualitative approaches, focus groups of family medicine residents were
      conducted. The resulting data were audiotaped and transcribed verbatim.
      Independent and team analysis was both iterative and interpretive. RESULTS: Data
      obtained from the focus groups revealed findings relating to the following
      categories: (1) perceived facilitators to practicing primary care obstetrics, (2)
      perceived barriers to practicing primary care obstetrics, and (3) learner
      experiences at the fulcrum of career decision making. CONCLUSION: Family medicine
      residents were encouraged by favorable learning experiences and group shared-call
      arrangements by their primary care obstetrics preceptors. Some concerns about a
      career including obstetrics persisted; however, positive experiences, including
      influential fulcrum points, may inspire family medicine residents to pursue a
      career involving primary care obstetrics.

PMID- 22399481
TI  - The influence of physician communication style on overweight patients'
      perceptions of length of encounter and physician being rushed.
AB  - BACKGROUND AND OBJECTIVES: Little is known about how patients and physicians
      perceive time and the extent to which they perceive the physician being rushed
      during encounters. One aim of this paper is to examine whether patient and
      physician characteristics and physician communication influence patient
      perception of the duration of the encounter and their perception of physicians
      being rushed. Another aim is to examine the relationship between patient and
      physician perceptions of physicians feeling rushed. METHODS: We audiorecorded 461
      encounters of overweight or obese patients with 40 primary care physicians and
      included 320 encounters in which weight was discussed. We calculated time spent
      with physician and coded all communication about weight using the Motivational
      Interview Treatment Integrity scale (MITI). Patients completed post-visit
      questionnaires in which they reported the estimated duration of the encounter and
      how rushed they thought the physician was during the encounter. Physicians
      reported how rushed they felt. RESULTS: Patients estimated encounters to be
      longer than they actually were by an average of 2.6 minutes (SD=11.0). When
      physicians used reflective statements when discussing weight, patients estimated
      the encounter to be shorter than when physicians did not use reflective
      statements (1.17 versus 4.56 minutes more than actual duration). Whites perceived
      the encounter as shorter than African Americans (1.45 versus 4.28 minutes more
      than actual duration). Physicians felt rushed in 66% of visits; however, most
      patients did not perceive this. Internists were perceived to be more rushed than
      family physicians. CONCLUSIONS: There is wide variation in patients' ability to
      estimate the length of time they spend with their physician. Some physician and
      patient characteristics were related to patient perceptions of the length of the
      encounter. Reflective statements might lead patients to perceive encounters as
      shorter. Physicians, especially family physicians, appear able to conceal that
      they are feeling rushed.

PMID- 22399482
TI  - Needs assessment of family medicine residency programs and predoctoral 
      directors.
AB  - BACKGROUND AND OBJECTIVES: Both predoctoral directors and residency program
      directors are invested in the education of students in family medicine. However,
      the perspectives and goals of each group can be diverse. Improved collaboration
      between these groups of educators would be anticipated to enhance the education
      of students in family medicine, allow for greater interaction between family
      medicine resident and faculty physicians and students, and eventually entice more
      students to enter family medicine as a career. METHODS: We conducted a survey of
      family medicine residency program directors and predoctoral directors to assess
      the views of the members of each group on how they could be useful to the other
      group, how the other group could be more useful to them, and what the barriers
      are to successful collaboration. The survey was open for 1 month, and the
      response rate was a little over one third from both groups. RESULTS: We found
      that each group values its counterpart and finds them important in enhancing the
      success of family medicine, improving students' perceptions of family medicine,
      and attracting students to the field. The amount of contact between program
      directors and predoctoral directors is directly related to their geographical
      proximity. CONCLUSIONS: A collaborative effort between family medicine residency
      programs and predoctoral directors could increase medical students' interest in
      family medicine. The biggest barrier to an effective relationship is the
      perception of a lack of sufficient time to devote to improving the relationship.

PMID- 22399483
TI  - Osteopathic medical student learning competency.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this paper is to report on the
      development and implementation of a learning competency assessment survey for
      first-year medical students. We began by defining learning competencies in a
      manner that is parallel to the clinical competencies resulting in a self
      assessment survey of 1,998 first-year osteopathic medical students from 25
      osteopathic medical schools. Results from the online survey indicated that the
      internal structure of the instrument and the reliability of the items were
      strong. The survey revealed that first-year medical students were most confident
      in their ability to perform in a professional manner and least confident in their
      ability to manage their curriculum, particularly with the assistance of faculty
      and advisors. A regression analysis indicated that the best predictors of
      curricular involvement were Student Learning and Improvement, Knowledge of
      Osteopathic Philosophy and Skills, Interpersonal Communication, and Systems
      Knowledge. However, Medical Knowledge and Professionalism did not provide any
      unique variance to the model, suggesting that students' confidence in their
      undergraduate science training or self perceptions of their professionalism had
      little to do with their confidence in navigating medical school.

PMID- 22399484
TI  - A pilot study of training family medicine residents in procedural skills at a
      community health center.
AB  - BACKGROUND AND OBJECTIVES: There are many challenges to providing procedural
      skills training as well as exposure to rural practice for family medicine
      residents, especially within the allowed hours of training. METHODS: A curriculum
      for self study was developed based on a Society of Teachers of Family Medicine
      consensus statement on procedural skills, resident interest and faculty
      experience. An agreement to offer a pilot procedural clinic at a community health
      center staffed by a family medicine faculty and resident was negotiated and
      delivered. Residents completed an evaluation of the experience. RESULTS: One
      faculty and 13 residents delivered 19 different procedures, with a total of 65
      procedures, over an 11-month period at a community health center. Minor barriers
      to providing services such as initially low referral rates and lack of
      instruments were overcome. CONCLUSIONS: Residents agreed that participating in
      this clinic increased the likelihood of adding procedures to their clinical
      practice and enhanced their appreciation for practice in a rural setting but may
      not have impacted their likelihood of practicing in a rural area.

PMID- 22399485
TI  - I am a family doctor.

PMID- 22399486
TI  - Leadership to transform practice: how do we wear our words?

PMID- 22399487
TI  - Clinical significance of baseline platelet reactivity in patients with acute
      coronary syndrome.
AB  - The aim of this study was to assess the baseline platelet hyperactivity in
      patients with acute coronary syndrome (ACS) and correlate it with the disease
      severity and clinical outcome. PARTICIPANTS AND METHODS: This study was conducted
      on 60 patients with the first attack of non-ST-segment elevation ACS and 30
      healthy controls. Patients were subdivided into 2 groups: group I: 40 patients
      with non-ST-segment elevation myocardial infarction (NSTEMI) and group II: 20
      patients with unstable angina. All the studied patients were subjected to
      baseline platelet function analysis using platelet function analyzer 100 (PFA
      100). RESULTS: Group I patients showed significantly lower PFA-100 closure time
      (CT) than group II (P = .04) and control group (P = .03). The occurrence of
      complications in NSTEMI patients was associated with older age, hypertension, and
      shorter baseline collagen adenosine diphosphate PFA-100 CT (P < .05). CONCLUSION:
      NSTEMI patients proved to have enhanced platelet function that can be used as a
      predictor of the outcome.

PMID- 22399489
TI  - Differential expression and function of alternative splicing variants of human
      liver X receptor alpha.
AB  - The liver X receptor alpha (LXRalpha) is a nuclear receptor that is involved in
      regulation of lipid metabolism, cellular proliferation and apoptosis, and
      immunity. In this report, we characterize three human LXRalpha isoforms with
      variation in the ligand-binding domain (LBD). While examining the expression of
      LXRalpha3, which lacks 60 amino acids within the LBD, we identified two novel
      transcripts that encode LXRalpha-LBD variants (LXRalpha4 and LXRalpha5).
      LXRalpha4 has an insertion of 64 amino acids in helix 4/5, and LXRalpha5 lacks
      the C-terminal helices 7 to 12 due to a termination codon in an additional exon
      that encodes an intron in the LXRalpha1 mRNA. LXRalpha3, LXRalpha4, and LXRalpha5
      were expressed at lower levels compared with LXRalpha1 in many human tissues and
      cell lines. We also observed weak expression of LXRalpha3 and LXRalpha4 in
      several tissues of mice. LXR ligand treatment induced differential regulation of
      LXRalpha isoform mRNA expression in a cell type-dependent manner. Whereas
      LXRalpha3 had no effect, LXRalpha4 has weak transactivation, retinoid X receptor
      (RXR) heterodimerization, and coactivator recruitment activities. LXRalpha5
      interacted with a corepressor in a ligand-independent manner and inhibited
      LXRalpha1 transactivation and target gene expression when overexpressed.
      Combination of LXRalpha5 cotransfection and LXRalpha antagonist treatment
      produced additive effects on the inhibition of ligand-dependent LXRalpha1
      activation. We constructed structural models of the LXRalpha4-LBD and its
      complexes with ligand, RXR-LBD, and coactivator peptide. The models showed that
      the insertion in the LBD can be predicted to disrupt RXR heterodimerization.
      Regulation of LXRalpha pre-mRNA splicing may be involved in the pathogenesis of
      LXRalpha-related diseases.

PMID- 22399488
TI  - Small-molecule targeting of proliferating cell nuclear antigen chromatin
      association inhibits tumor cell growth.
AB  - Proliferating cell nuclear antigen (PCNA), a potential anticancer target, forms a
      homotrimer and is required for DNA replication and numerous other cellular
      processes. The purpose of this study was to identify novel small molecules that
      modulate PCNA activity to affect tumor cell proliferation. An in silico screen of
      a compound library against a crystal structure of PCNA and a subsequent
      structural similarity search of the ZINC chemical database were carried out to
      derive relevant docking partners. Nine compounds, termed PCNA inhibitors (PCNA
      Is), were selected for further characterization. PCNA-I1 selectively bound to
      PCNA trimers with a dissociation constant (K(d)) of ~0.2 to 0.4 MUM. PCNA-Is
      promoted the formation of SDS-refractory PCNA trimers. PCNA-I1 dose- and time
      dependently reduced the chromatin-associated PCNA in cells. Consistent with its
      effects on PCNA trimer stabilization, PCNA-I1 inhibited the growth of tumor cells
      of various tissue types with an IC(50) of ~0.2 MUM, whereas it affected the
      growth of nontransformed cells at significantly higher concentrations (IC(50),
      ~1.6 MUM). Moreover, uptake of BrdU was dose-dependently reduced in cells treated
      with PCNA-I1. Mechanistically the PCNA-Is mimicked the effect of PCNA knockdown
      by siRNA, inducing cancer cell arrest at both the S and G(2)/M phases. Thus, we
      have identified a class of compounds that can directly bind to PCNA, stabilize
      PCNA trimers, reduce PCNA association with chromatin, and inhibit tumor cell
      growth by inducing a cell cycle arrest. They are valuable tools in studying PCNA
      function and may be useful for future PCNA-targeted cancer therapy.

PMID- 22399492
TI  - Survival comparisons between haemodialysis and peritoneal dialysis.

PMID- 22399491
TI  - Increased urinary excretion of angiotensinogen is associated with risk of chronic
      kidney disease.
AB  - BACKGROUND: The effect of intrarenal renin-angiotensin system (RAS) activity on
      risk of chronic kidney disease (CKD) has not been well studied in human subjects.
      METHODS: We investigated the association between urinary angiotensinogen, a
      reliable biomarker of intrarenal RAS activity, and risk of CKD in 201 patients
      and 201 controls. CKD was defined as estimated glomerular filtration rate (eGFR)
      < 60 mL/min/1.73 m(2) or presence of albuminuria ( >= 30 mg/24 h). RESULTS:
      Compared to controls, median urinary angiotensinogen excretion (45.4 versus 7.4
      MUg/24 h, P < 0.0001) and angiotensinogen-to-creatinine ratio (26.3 versus 4.4
      MUg/g, P < 0.0001) were significantly higher in patients with CKD. Log
      transformed urinary angiotensinogen excretion and angiotensinogen-to-creatinine
      ratio were inversely correlated with eGFR (r = -0.59 and -0.57, both P < 0.0001)
      and positively correlated with log-transformed urinary albumin excretion (r =
      0.89 and 0.87, both P < 0.0001). After adjusting for multiple covariables,
      including the use of angiotensin-converting enzyme inhibitors and/or angiotensin
      II receptor blockers, diuretics and statins, the odds ratios (95% confidence
      interval) for CKD comparing the highest tertile to the lowest two tertiles of
      urinary angiotensinogen excretion and angiotensinogen-to-creatinine ratio were
      6.70 (3.43, 13.1; P < 0.0001) and 6.45 (3.34, 12.4; P < 0.0001), respectively.
      CONCLUSIONS: These data indicate the intrarenal RAS may play an important role in
      the etiology of CKD, and urinary angiotensinogen may be a useful clinical
      biomarker for the identification of patients at a high risk for CKD.

PMID- 22399493
TI  - Cystatin C in HIV-infected patients: promising but not yet ready for prime time.
AB  - With the development of highly active antiretroviral therapy, chronic kidney
      disease has become a prominent cause of morbidity in individuals infected by HIV.
      Because serum creatinine has significant limitations in this specific population,
      cystatin C is emerging as a promising biomarker for both the evaluation of
      glomerular filtration rate (GFR) and the detection of drug-induced kidney injury.
      Along with renal function, serum cystatin C concentration is associated with
      several biological parameters such as C-reactive protein, HIV viral load and CD4+
      cells count. All these determinants of cystatin C are, however, more or less
      independent of GFR. Studies evaluating the accuracy of cystatin C for estimating
      GFR in the setting of HIV infection are scarce and methodology is often
      questionable (lack of reference method or inadequate statistical analyses). Thus
      far, data are insufficient to encourage the use of cystatin C or cystatin C-based
      equations to estimate GFR in the HIV-infected population. Further research is
      needed to explore the clinical utility of cystatin C in this setting. Beyond the
      use of cystatin C as a GFR marker, future studies will have to evaluate its role
      as a predictor of patient outcome, particularly in regard to cardiovascular morbi
      mortality.

PMID- 22399494
TI  - The balance of beneficial and deleterious effects of hypoxia-inducible factor
      activation by prolyl hydroxylase inhibitor in rat remnant kidney depends on the
      timing of administration.
AB  - BACKGROUND: Chronic hypoxia in the kidney has been suggested as a final common
      pathway in the progression of chronic kidney disease (CKD) leading to eventual
      kidney failure. Hypoxia-inducible factor (HIF) activation might offer a promising
      approach to the protection of hypoxic tissues, but the effect of HIF activation
      on CKD is still controversial. In this study, we investigated whether HIF
      activation had a beneficial or deleterious effect on CKD in the rat remnant
      kidney (RK) model. METHODS: One week after a subtotal nephrectomy, rats were
      randomized and each received special administration of prolyl hydroxylases (PHD)
      inhibitor L-mimosine (L-Mim) as follows: in the early long-time L-Mim treatment
      group they were administered L-Mim at Weeks 2-12; in the advanced medium-term L
      Mim treatment group they were administered L-Mim at Weeks 4-12 and in the end
      stage L-Mim treatment group they were administered L-Mim at Weeks 8-12. RESULTS:
      Compared with the control group, renal dysfunction and increased collagen III
      deposition, alpha-smooth muscle actin expression and ED-1-positive macrophage
      infiltration in tubulointerstitium were exacerbated by early long-term L-Mim
      treatment and improved by advanced medium-term L-Mim treatment. End-stage L-Mim
      treatment had no effect on RK rats. Furthermore, early long-term L-Mim treatment
      activated HIF-1alpha, connective tissue growth factor (CTGF) and phospho-Smad3
      prominently throughout the time course and activated HIF-2alpha, vascular
      endothelial growth factor (VEGF) and erythropoietin (EPO) slightly at the end
      stage, while advanced medium-term L-Mim treatment activated HIF-2alpha, VEGF and
      EPO significantly and had no effect on HIF-1alpha, CTGF and phospho-Smad3.
      CONCLUSION: HIF-alpha activation by PHD inhibitor L-Mim has dual roles in the
      development of CKD in the rat RK model depending on the timing of the
      administration and possibly the activated isoform of HIF-alpha.

PMID- 22399495
TI  - 'Nurses do assess pain, they just don't write it down!'.

PMID- 22399497
TI  - Screening for epigenetically masked genes in colorectal cancer Using 5-Aza-2'
      deoxycytidine, microarray and gene expression profile.
AB  - AIM: Unearthing of silenced genes in colorectal cancer (CRC). MATERIALS AND
      METHODS: Oligonucleotide microarray was used in order to find changes in gene
      expression in five CRC cell lines before and after 5-aza-2'-Deoxycitidine
      treatment. Up-regulated genes were integrated with expression profile of matched
      colorectal tissue samples. Methylation-specific polymerase chain reaction and
      Real-time quantitative reverse transcription polymerase chain reaction were used
      to further analyze candidates using 15 CRC cell lines and 23 paired samples.
      RESULTS: After applying study selection criteria for 68 genes obtained from
      integrated arrays, we identified 16 genes; apoptosis-stimulating of p53 protein
      1(ASPP1) and Scavenger receptor class A, member 5 (SCARA5) were selected for
      further analysis. Methylation was only identified for SCARA5 in 20% of the cell
      lines and in 17% of tumor the samples. Down expression of SCARA5 was observed in
      CRC cell lines and in tumor samples compared to normal (p<0.001 and p=0.001,
      respectively). CONCLUSION: Genome-wide screening identifies genes potentially
      affected by methylation in CRC. SCARA5 may have a role in tumorigenesis in CRC.

PMID- 22399496
TI  - Targeting PI3K and RAD51 in Barrett's adenocarcinoma: impact on DNA damage
      checkpoints, expression profile and tumor growth.
AB  - Phosphatidylinositol 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog
      1 (AKT) signaling in cancer is implicated in various survival pathways including
      regulation of recombinase (RAD51). In this study, we evaluated PI3K and RAD51 as
      targets in Barrett's adenocarcinoma (BAC) cells both in vitro and in vivo. BAC
      cell lines (OE19, OE33, and FLO-1) were cultured in the presence of PI3K
      inhibitor (wortmannin) and the impact on growth and expression of AKT,
      phosphorylated-AKT (P-AKT), and RAD51 was determined. Wortmannin induced growth
      arrest and apoptosis in two BAC cell lines (OE33 and OE19), which had relatively
      higher expression of AKT. FLO-1 cells, with lower AKT expression, were less
      sensitive to treatment and investigated further. In FLO-1 cells, wortmannin
      suppressed ataxia telangiectasia and Rad3-related protein (ATR)-checkpoint kinase
      1 (CHK1)-mediated checkpoint and multiple DNA repair genes, whereas RAD51 and
      CHK2 were not affected. Western blotting confirmed that RAD51 was suppressed by
      wortmannin in OE33 and OE19 cells, but not in FLO-1 cells. Suppression of RAD51
      in FLO-1 cells down-regulated the expression of CHK2 and CHK1, and reduced the
      proliferative potential. Finally, the suppression of RAD51 in FLO-1 cells,
      significantly increased the anticancer activity of wortmannin in these cells,
      both in vitro and in vivo. We show that PI3K signaling and hsRAD51, through
      distinct roles in DNA damage response and repair pathways, provide survival
      advantage to BAC cells. In cells with inherent low expression of AKT, RAD51 is
      unaffected by PI3K suppression and provides an additional survival pathway.
      Simultaneous suppression of PI3K and RAD51, especially in cells with lower AKT
      expression, can significantly reduce their proliferative potential.

PMID- 22399498
TI  - Preclinical rationale for combining an EGFR antibody with cisplatin/gemcitabine
      for the treatment of NSCLC.
AB  - BACKGROUND: Although the addition of epidermal growth factor receptor (EGFR)
      antibodies to various platinum-based chemotherapy regimens for non-small cell
      lung cancer (NSCLC) is being actively pursued in the clinic, rationale for the
      prioritization of specific regimens is lacking. MATERIALS AND METHODS: We
      evaluated the antitumor effects of necitumumab, a recombinant human IgG1 antibody
      targeting EGFR, in combination with cisplatin plus gemcitabine, pemetrexed, or
      paclitaxel in a panel of 9 subcutaneous tumor models of NSCLC established in
      nu/nu athymic mice. RESULTS: Necitumumab in combination with
      cisplatin/gemcitabine was particularly effective, although interestingly, the
      mechanisms underlying these benefits were model dependent. For example, increased
      tumor cell apoptosis contributed towards combination efficacy in the A549 model,
      in association with increased expression of hsa-miR-29b and reduced expression of
      antiapoptotic genes including DNA methyltransferase DNMT3B, commonly up-regulated
      in patients with NSCLC. Such inverse effects of combination therapy on DNMT3B and
      hsa-miR-29b expression were found in multiple models. Importantly, in the A549
      model, hsa-miR-29b down-regulation of DMNT3b reduced promoter methylation of
      tumor suppressor genes such as Cell adhesion molecule 1 (CADM1), Ras associated
      (RalGDS/AF-6) domain family member 1 (RASSF1), and Fragile histidine triad gene
      (FHIT), increasing their expression. CONCLUSION: These results offer a
      preclinical rationale for combining an EGFR antibody with cisplatin/gemcitabine
      for patients with NSCLC, and provide potential molecular biomarkers for tailoring
      therapy.

PMID- 22399499
TI  - Proteomic analysis of differently archived breast cancer tissues.
AB  - Currently, the most common practice of human breast tissue preservation is
      formalin fixation which ensures good quality for histopathological analyses but
      damages DNA, RNA, and proteins, impairing their usefulness for molecular analysis
      and biomarker investigations. We investigated the potential value of a non-toxic
      fixative for sparing proteins preserved in paraffin-embedded breast biopsies.
      Specimens were fixed in formalin-free fixative prior to paraffin embedding, and
      then processed for quality and quantity of protein conservation. Similar protein
      patterns were observed in formalin-free fixative and frozen tissues using mono-
      and bi-dimensional electrophoresis, as well as western blotting. Protein patterns
      assessed by mass spectrometric analysis were found to be identical for frozen and
      formalin-free-fixed tissues. Immunohistochemistry using various antibodies showed
      comparable results for both tissue storage methods. In conclusion, we believe
      that formalin-free fixative represents an easy-to-use alternative to formalin for
      archived tissue and for biomarker investigations, since it simultaneously
      protects both the histomorphology and the integrity of macromolecules.

PMID- 22399500
TI  - Proteomic identification of chaperonin-containing tail-less complex polypeptide-1
      gamma subunit as a p53-responsive protein in colon cancer cells.
AB  - We recently reported that functional loss of p53 altered the responses of human
      HCT116 colon cancer cells to apoptosis triggers. To examine the molecular basis
      underlying the differential responses to drug treatment in the cancer cells, we
      performed a proteomic analysis in order to compare the protein expressions
      between human colon cancer cells with and those without p53 (p53(+/+) and p53(-/
      )) respectively. We identified two isoelectric variants of the chaperonin
      containing tail-less complex polypeptide-1 gamma subunit (TCP-1gamma) from the
      cells, and confirmed that the two isoelectric variants were phosphorylated at
      tyrosine residue(s). The p53(-/-) cells had higher protein concentration of the
      more acidic variant of TCP-1gamma compared to their p53(+/+) counterparts.
      Moreover, TCP-1gamma was found to be co-localized with centrosome. Our results
      implicate a novel cell signaling loop in HCt116 cells involving p53 and TCP1
      gamma phosphorylation, which may be related to regulation and action of
      centrosomes.

PMID- 22399501
TI  - Impaired crosstalk between pulsatile insulin and glucagon secretion in
      prediabetic individuals.
AB  - INTRODUCTION: Postprandial hyperglucagonemia is frequently found in patients with
      diabetes. Recently, a loss of the inverse relationship between pulsatile insulin
      and glucagon secretion has been reported in patients with type 2 diabetes. The
      crosstalk between pulsatile islet hormone secretion in prediabetic individuals
      has not yet been examined. PATIENTS AND METHODS: Eleven individuals with impaired
      glucose tolerance and/or impaired fasting glucose and 13 nondiabetic controls
      were examined after mixed meal ingestion. Glucose, insulin, and glucagon levels
      were determined frequently and analyzed by deconvolution and cross-correlation
      methods. RESULTS: Postprandial glucose levels were higher in prediabetic
      individuals (P = 0.017). Insulin concentrations were not different between the
      groups (P = 0.29). Postprandial glucagon levels were higher in the impaired
      glucose tolerance/impaired fasting glucose individuals (P = 0.039). Pulsatile
      insulin and glucagon secretion was apparent in both groups, but there were no
      differences in the frequency or mass of insulin and glucagon pulses between the
      groups. An inverse relationship between the insulin and glucagon concentration
      time curves was found in the control subjects (P < 0.05). This association was
      not detectable in the prediabetic individuals. CONCLUSIONS: Increased
      postprandial glucagon concentrations in prediabetic individuals are accompanied
      by a loss of the pulsatile insulin-glucagon crosstalk. This suggests that
      disturbances in islet hormone pulsatility precede the actual manifestation of
      hyperglycemia.

PMID- 22399502
TI  - The Adrenal Vein Sampling International Study (AVIS) for identifying the major
      subtypes of primary aldosteronism.
AB  - CONTEXT: In patients who seek surgical cure of primary aldosteronism (PA), The
      Endocrine Society Guidelines recommend the use of adrenal vein sampling (AVS),
      which is invasive, technically challenging, difficult to interpret, and commonly
      held to be risky. OBJECTIVE: The aim of this study was to determine the
      complication rate of AVS and the ways in which it is performed and interpreted at
      major referral centers. DESIGN AND SETTINGS: The Adrenal Vein Sampling
      International Study is an observational, retrospective, multicenter study
      conducted at major referral centers for endocrine hypertension worldwide.
      PARTICIPANTS: Eligible centers were identified from those that had published on
      PA and/or AVS in the last decade. MAIN OUTCOME MEASURE: The protocols,
      interpretation, and costs of AVS were measured, as well as the rate of adrenal
      vein rupture and the rate of use of AVS. RESULTS: Twenty of 24 eligible centers
      from Asia, Australia, North America, and Europe participated and provided
      information on 2604 AVS studies over a 6-yr period. The percentage of PA patients
      systematically submitted to AVS was 77% (median; 19-100%, range). Thirteen of the
      20 centers used sequential catheterization, and seven used bilaterally
      simultaneous catheterization; cosyntropin stimulation was used in 11 centers. The
      overall rate of adrenal vein rupture was 0.61%. It correlated directly with the
      number of AVS performed at a particular center (P = 0.002) and inversely with the
      number of AVS performed by each radiologist (P = 0.007). CONCLUSIONS: Despite
      carrying a minimal risk of adrenal vein rupture and at variance with the
      guidelines, AVS is not used systematically at major referral centers worldwide.
      These findings represent an argument for defining guidelines for this clinically
      important but technically demanding procedure.

PMID- 22399503
TI  - A stimulatory thyrotropin receptor antibody enhances hyaluronic acid synthesis in
      graves' orbital fibroblasts: inhibition by an IGF-I receptor blocking antibody.
AB  - CONTEXT: Graves' ophthalmopathy (GO) is characterized by expanded volume of the
      orbital fat and extraocular muscle tissues and elevated levels of TSH receptor
      autoantibodies (TRAb). The expansion of orbital tissues involves accumulation of
      hyaluronic acid (HA) within the orbit. OBJECTIVE: The objective of the study was
      to determine whether a monoclonal stimulatory TRAb (M22) impacts HA synthesis in
      GO orbital cells and, if so, whether this might be blocked by an IGF-I receptor
      (IGF-IR)-blocking antibody (1H7) or inhibitors of various downstream signaling
      cascades. DESIGN: GO orbital fibroblast cultures (n = 6) were treated with M22,
      bovine TSH (bTSH), or IGF-I in serum-free medium. Some cultures also received
      1H7, LY294002, rapamycin, or protein kinase A inhibitor. MAIN OUTCOME MEASURES:
      HA production and phosphorylated Akt levels in media or immunoblotting for
      phosphorylated Akt were measured. RESULTS: M22 or bTSH stimulated HA synthesis
      (2.1-fold with 100 ng/ml M22 and 1.9-fold with 10 U/liter bTSH; P < 0.05 each).
      M22-induced HA synthesis was inhibited by LY294002 or rapamycin but not by
      protein kinase inhibitor. HA synthesis stimulated by M22 or IGF-I was inhibited
      by 1H7 (mean 36.6 +/- 5.6% and mean 45.8 +/- 7.6%, respectively; P < 0.05 each).
      Similarly, M22- or IGF-I-stimulated Akt phosphorylation was inhibited by 1H7
      (mean 54 +/- 9.6 and 36.1 +/- 8.8%, respectively; P = 0.01 each). CONCLUSIONS:
      The stimulatory TRAb M22 increases HA production in undifferentiated GO orbital
      fibroblasts via phosphoinositide 3-kinase/phosphorylated AKT/mammalian target of
      rapamycin activation. Blockade of IGF-IR inhibits both HA synthesis and Akt
      phosphorylation induced by M22 or IGF-I in these cells, suggesting that TSH
      receptor and IGF-IR signaling may be closely linked in the GO orbit.

PMID- 22399504
TI  - Genetic variation in the glucose-dependent insulinotropic polypeptide receptor
      modifies the association between carbohydrate and fat intake and risk of type 2
      diabetes in the Malmo Diet and Cancer cohort.
AB  - CONTEXT: A common genetic variant (rs10423928, A-allele) in the glucose-dependent
      insulinotropic polypeptide receptor gene (GIPR) is associated with decreased
      insulin secretion. Glucose-dependent insulinotropic polypeptide is secreted after
      food consumption and gipr knockout mice fed a high-fat diet are protected against
      obesity and disturbances in glucose homeostasis. OBJECTIVE: Our objective was to
      examine the interactions between rs10423928 and macronutrients and fiber intakes
      on body mass index and type 2 diabetes risk. DESIGN, SETTING, AND PARTICIPANTS:
      Among nondiabetic subjects in the Swedish population-based Malmo Diet and Cancer
      cohort (n = 24,840; 45-74 yr), 1541 diabetes cases were identified during 12 yr
      of follow-up. Dietary intakes were assessed using a diet history method. MAIN
      OUTCOME MEASURE: Incident type 2 diabetes was identified through registers.
      RESULTS: There was no indication that dietary intakes significantly modify the
      association between GIPR genotype and body mass index (P interaction >0.08). We
      observed significant interactions between GIPR genotype and quintiles of
      carbohydrate (P = 0.0005) and fat intake (P = 0.0006) on incident type 2
      diabetes. The TT-genotype carriers within the highest compared with the lowest
      carbohydrate quintile were at 23% (95% confidence interval = 5-39%) decreased
      type 2 diabetes risk. In contrast, AA-genotype carriers in the highest compared
      with the lowest fat quintile were at 69% (95% confidence interval = 29-86%)
      decreased risk. CONCLUSIONS: Our prospective, observational study indicates that
      the type 2 diabetes risk by dietary intake of carbohydrate and fat may be
      dependent on GIPR genotype. In line with results in gipr knockout mice, AA
      genotype carriers consuming high-fat low-carbohydrate diets had reduced type 2
      diabetes risk, whereas high-carbohydrate low-fat diets benefitted the two thirds
      of population homozygous for the T-allele.

PMID- 22399506
TI  - "Donohue syndrome".

PMID- 22399505
TI  - An update on the screening, diagnosis, management, and treatment of vitamin D
      deficiency in individuals with cystic fibrosis: evidence-based recommendations
      from the Cystic Fibrosis Foundation.
AB  - OBJECTIVE: The objective was to develop evidence-based clinical care guidelines
      for the screening, diagnosis, management, and treatment of vitamin D deficiency
      in individuals with cystic fibrosis (CF). PARTICIPANTS: The guidelines committee
      was comprised of physicians, registered dietitians, a pharmacist, a nurse, a
      parent of an individual with CF, and a health scientist, all with experience in
      CF. PROCESS: Committee members developed questions specific to vitamin D health
      in individuals with CF. Systematic reviews were completed for each question. The
      committee reviewed and graded the available evidence and developed evidence-based
      recommendations and consensus recommendations when insufficient evidence was
      available. Each consensus recommendation was voted upon by an anonymous process.
      CONCLUSIONS: Vitamin D deficiency is common in CF. Given the limited evidence
      specific to CF, the committee provided consensus recommendations for most of the
      recommendations. The committee recommends yearly screening for vitamin D status,
      preferably at the end of winter, using the serum 25-hydroxyvitamin D measurement,
      with a minimal 25-hydroxyvitamin D concentration of 30 ng/ml (75 nmol/liter)
      considered vitamin D sufficient in individuals with CF. Recommendations for age
      specific vitamin D intake for all individuals with CF, form of vitamin D, and a
      stepwise approach to increase vitamin D intake when optimal vitamin D status is
      not achieved are delineated.

PMID- 22399507
TI  - Fat mass and lipid profile in young adults born preterm.
AB  - CONTEXT: Associations between small size at birth and abnormal cardiovascular
      parameters in later life have been reported. It is, however, unknown whether the
      effect of a small size at birth on cardiovascular risk factors in later life is
      due to a small size for gestational age or due to prematurity. Due to advances in
      neonatal care, survival of preterm infants has significantly improved, and
      nowadays an increasing number of these children reach adulthood. It is,
      therefore, of increasing importance to assess the long-term effect of prematurity
      on determinants for cardiovascular disease. OBJECTIVE: The aim of the study was
      to assess the long-term effects of gestational age and particularly preterm birth
      on lipid levels and fat mass in early adulthood. DESIGN AND PATIENTS: A cross
      sectional study was conducted with 455 healthy subjects, aged 18 to 24 yr; 167
      preterm subjects were compared with 288 full-term subjects. OUTCOME MEASURE:
      Total fat mass, trunk fat mass, and limb fat mass were determined by dual-energy
      x-ray absorptiometry. Furthermore, fasting lipid levels (total cholesterol, low
      density lipoprotein, triglyceride, apolipoprotein B, lipoprotein a, high-density
      lipoprotein, and apolipoprotein A-I) were measured. RESULTS: Preterm subjects had
      a significantly higher percentage of total fat mass, trunk fat mass, and limb fat
      mass than subjects born term. Furthermore, preterm subjects had significantly
      lower serum lipoprotein a levels and higher apolipoprotein A-I levels than term
      subjects. Multiple linear regression analyses to assess the association between
      gestational age and fat mass and lipid levels showed similar results. CONCLUSION:
      In our cohort of 455 young adults, preterm birth was associated with more total
      fat mass, trunk fat, and limb fat mass but a relatively favorable lipid profile.

PMID- 22399508
TI  - Biological relevance of medullary thyroid microcarcinoma.
AB  - CONTEXT: The clinical relevance of medullary thyroid microcarcinoma, a calcitonin
      secreting malignancy, as a valid target for biochemical screening programs has
      been called into doubt. OBJECTIVE: This investigation aimed at clarifying the
      intensity of lymphatic spread and exploring the potential for biochemical cure in
      medullary thyroid microcarcinoma. DESIGN: This was a retrospective analysis.
      SETTING: The setting was a tertiary referral center. PATIENTS: Included were 233
      patients with hereditary (126 patients) or sporadic (107 patients) medullary
      thyroid microcarcinoma. INTERVENTIONS: The intervention was compartment-oriented
      surgery. MAIN OUTCOME MEASURE: Clinical-histopathological variables were
      stratified by primary tumor diameter (2-mm increments) and biochemical cure.
      RESULTS: With incremental tumor diameter, increasingly more patients with
      medullary thyroid microcarcinoma harbored lymph node metastases: from 6 to 62% of
      patients (P < 0.001) for hereditary and from 13 to 43% of patients (P = 0.01) for
      sporadic disease. The corresponding biochemical cure rates declined from 96 to
      71% (P = 0.001) and from 85 to 77% (P = 0.01). Distant disease (two instances of
      lung metastasis and one instance of bone and liver metastasis) was exceptional,
      affecting 1.3% of patients with medullary thyroid microcarcinoma. Strongest
      predictors of a patient's failure to achieve normal calcitonin serum levels were
      positive nodal status (79 vs. 11% in hereditary and 79 vs. 12% in sporadic
      disease; both P < 0.001) and the number of involved nodes (means of 6.6 vs. 0.3
      nodes in hereditary and 8.8 vs. 0.4 nodes in sporadic disease; both P < 0.001).
      CONCLUSIONS: Sporadic and hereditary medullary thyroid microcarcinoma carry a
      significant risk of lymph node metastasis and postoperative calcitonin elevation.

PMID- 22399509
TI  - Recovery of the hypothalamic-pituitary-adrenal axis in children and adolescents
      after surgical cure of Cushing's disease.
AB  - CONTEXT: Recovery of the hypothalamic-pituitary-adrenal axis (HPAA) after
      transsphenoidal surgery (TSS) for Cushing's disease (CD) in children has not been
      adequately studied. OBJECTIVE: Our objective was to assess time to recovery of
      the HPAA after TSS in children with CD. DESIGN AND SETTING: This was a case
      series at the National Institutes of Health Clinical Center. PATIENTS: Fifty
      seven patients with CD (6-18 yr, mean 13.0 +/- 3.1 yr) given a standard regimen
      of glucocorticoid tapering after TSS were studied out of a total of 73 recruited.
      INTERVENTIONS: ACTH (250 MUg) stimulation tests were administered at
      approximately 6-month intervals for up to 36 months. Age, sex, pubertal status,
      body mass index, length of disease, midnight cortisol, and urinary free cortisol
      at diagnosis were analyzed for effects on recovery. MAIN OUTCOME MEASURE: The
      main outcome measure was complete recovery of the HPAA as defined by a cortisol
      level of at least 18 MUg/dl in response to 250 MUg ACTH. RESULTS: Full recovery
      was reached by 43 (75.4%) of 57 patients, with 29 of the 43 (67.4%) and 41 of the
      43 (95.3%) recovering by 12 and 18 months, respectively. The overall mean time to
      recovery was 12.6 +/- 3.3 months. Kaplan-Meier survivor function estimated a 50%
      chance of recovering by 12 months after TSS and 75% chance of recovering within
      14 months. By receiver operating characteristic curve assessment, the cutoff of
      at least 10-11 MUg/dl of cortisol as the peak of ACTH stimulation testing at 6
      months after TSS yielded the highest sensitivity (70-80%) and specificity (64
      73%) to predict full recovery of the HPAA at 12 months. Two of the four patients
      that recovered fully within 6 months had recurrent CD. CONCLUSIONS: Although this
      is not a randomized study, we present our standardized tapering regimen for
      glucocorticoid replacement after TSS that led to recovery of the HPAA in most
      patients within the first postoperative year. Multiple factors may affect this
      process, but an early recovery may indicate disease recurrence.

PMID- 22399510
TI  - Cost-effectiveness of universal and risk-based screening for autoimmune thyroid
      disease in pregnant women.
AB  - CONTEXT: Hypothyroidism in pregnancy can lead to adverse maternal and fetal
      outcomes. Although screening of high-risk women is advocated, universal screening
      remains controversial. OBJECTIVE: The objective of the study was to compare the
      cost-effectiveness of universal screening of pregnant women for autoimmune
      thyroid disease (AITD) with screening only high-risk women and with no screening.
      DESIGN, SETTING, AND PARTICIPANTS: A decision-analytic model compared the
      incremental cost per quality-adjusted life-year (QALY) gained among the
      following: 1) universal screening, 2) high-risk screening, and 3) no screening.
      Screening consisted of a first-trimester thyroid-stimulating hormone level and
      antithyroid peroxidase antibodies. Women with abnormal results underwent further
      testing and, when indicated, levothyroxine therapy. Randomized controlled trials
      provided probabilities for adverse obstetrical outcomes. The model accounted for
      the development of postpartum thyroiditis and overt hypothyroidism. Additional
      scenarios in which therapy prevented cases of decreased child intelligence
      quotient were explored. MAIN OUTCOME MEASURES: Medical consequences of AITD in
      pregnancy, QALY, and costs were measured. RESULTS: Risk-based screening and
      universal screening were both cost-effective relative to no screening, with
      incremental cost-effectiveness ratios (ICERs) of $6,753/QALY and $7,138/QALY,
      respectively. Universal screening was cost-effective compared with risk-based
      screening, with an ICER of $7,258/QALY. Screening remained cost-effective in
      various clinical scenarios, including when only overt hypothyroidism was assumed
      to have adverse obstetrical outcomes. Universal screening was cost-saving in the
      scenario of untreated maternal hypothyroidism resulting in decreased child
      intelligence, with levothyroxine therapy being preventive. CONCLUSIONS: Universal
      screening of pregnant women in the first trimester for AITD is cost-effective,
      not only compared with no screening but also compared with screening of high-risk
      women.

PMID- 22399511
TI  - Circulating sclerostin levels and bone turnover in type 1 and type 2 diabetes.
AB  - CONTEXT: Previous observations showed a condition of low bone turnover and
      decreased osteoblast activity in both type 1 and 2 diabetes mellitus (DM1 and
      DM2). Sclerostin is a secreted Wnt antagonist produced by osteocytes that
      regulates osteoblast activity and thus bone turnover. Its levels increase with
      age and are regulated by PTH. OBJECTIVES: The aim of the present study was to
      evaluate circulating sclerostin levels in patients with DM1 or DM2 with normal
      renal function and to analyze its relationship with PTH, 25-hydroxyvitamin D, and
      bone turnover markers. DESIGN, AND SETTING: This was a cross-sectional study
      conducted at a clinical research center. PARTICIPANTS: Forty DM2 and 43 DM1
      patients were studied and compared with a reference control group (n = 83).
      RESULTS: In the overall cohort, sclerostin levels were higher in males than in
      females and significantly increased with age in both genders. The positive
      correlation between sclerostin and age was maintained in DM1 but not in DM2
      patients. Moreover, sclerostin levels were higher in DM2 than in controls or DM1
      patients, and this difference persisted when adjustments were made for age and
      body mass index. Consistent with previous clinical and experimental observations,
      sclerostin was negatively associated with PTH in nondiabetic patients (r = -0.30;
      P < 0.01), independently of age and gender. Conversely, an opposite but
      nonsignificant trend between PTH and sclerostin was observed in both DM1 (r =
      0.26; P = 0.09) and DM2 (r = 0.32; P = 0.07) cohorts. CONCLUSIONS: These findings
      suggest that sclerostin is increased in DM2. Moreover, the transcriptional
      suppression of sclerostin production by PTH might be impaired in both DM1 and
      DM2.

PMID- 22399512
TI  - Serum BAFF concentrations in patients with Graves' disease and orbitopathy before
      and after immunosuppressive therapy.
AB  - INTRODUCTION: B cells are known to play a key role in the pathogenesis of
      autoimmune disease. B lymphocyte activating factor (BAFF), a member of TNF
      family, promotes autoantibody production by increasing B cell survival and
      proliferation. Serum BAFF concentrations have been found to be increased in
      systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome.
      OBJECTIVE: We have measured serum BAFF concentrations in patients with Graves'
      disease (GD) with or without Graves' orbitopathy (GO) and in active GO in
      relation to immunosuppressive treatment. METHODS: Forty-two patients and nine
      normal controls were studied. Thirty-four patients had GO, which was active in
      23. Of these, nine were treated with rituximab (RTX) and 14 with i.v.
      methylprednisolone (MP). Serum BAFF concentrations were measured at baseline in
      all patients, at peripheral B cell depletion and repopulation after RTX, and
      after therapy with MP. RESULTS: Serum basal BAFF concentrations in GD patients
      were significantly higher when compared with normal controls (P = 0.0001), and no
      difference was observed in those with active or inactive GO. Serum BAFF
      concentrations were also significantly correlated with serum antithyroglobulin
      antibodies (P = 0.04) but not with sex, age, smoking habits, therapy for thyroid
      disease, and serum antithyroperoxidase antibodies and TSH receptor antibodies.
      After RTX, there was an increase of serum BAFF concentrations at the time of B
      cell depletion (P = 0.02) but also at B cell repopulation (P = 0.04). In patients
      treated with MP, serum BAFF concentrations decreased significantly after therapy
      (P < 0.01). CONCLUSIONS: We report that serum BAFF concentrations are elevated in
      patients with GD, in whom hyperthyroidism is known to be based on a B-cell-driven
      pathophysiological mechanism. In active GO, BAFF further increases after therapy
      with RTX as a consequence of the B cell depletion per se. The decrease of serum
      BAFF after iv steroids suggests that MP may exert an immunosuppressive effect by
      modifying B-cell-derived immune reactions.

PMID- 22399513
TI  - Phenotypical analysis of lymphocytes with suppressive and regulatory properties
      (Tregs) and NK cells in the papillary carcinoma of thyroid.
AB  - CONTEXT: The immune system seems to play a key role in preventing metastasis and
      recurrence of thyroid cancer. T regulatory lymphocytes (Tregs) and natural killer
      (NK) cells play an important role in the dysfunction of the host immune system in
      cancer patients. OBJECTIVE: We investigated thyroid gland infiltration by Tregs
      and NK cells in patients with papillary thyroid cancer (PTC) and thyroid nodular
      goiter (TNG). The correlation between the extent of the disease and the
      lymphocytic infiltration of Tregs and NK cells was examined. DESIGN, SETTING, AND
      PARTICIPANTS: A total of 65 patients with PTC, 25 with TNG, and 50 healthy
      controls were studied. Blood and tissue samples from 28 patients with PTC and 13
      with TNG and blood samples from the healthy controls were analyzed for T4
      (CD3(+)CD4(+)), T8 (CD3(+)CD8(+)), NK (CD3(-)CD16(+)CD56(+)), and
      CD4(+)CD25(+)CD127(-/low) Tregs by flow cytometry (FC). Tissue samples were also
      analyzed for Foxp3(+) Tregs by immunohistochemistry. RESULTS: Tregs showed
      greater infiltration in thyroid tissue of PTC patients compared with patients
      with TNG (P < 0.0009 for FC and P < 0.0001 for immunohistochemistry); FC analysis
      of blood samples showed no difference between the groups. Flow cytometry analysis
      showed significantly increased NK cells in PTC tissue compared with TNG tissue (P
      = 0.037), whereas blood samples showed no difference. CD4(+) and CD8(+) T cells
      did not differ in blood and tissue samples. Increased Tregs tissue infiltration
      was positively correlated with advanced disease stage (P < 0.0026), whereas NK
      infiltration was negatively correlated (P < 0.0041). CONCLUSION: Tregs and NK
      cells may be important regulators of thyroid cancer progression.

PMID- 22399515
TI  - The results of CHD7 analysis in clinically well-characterized patients with
      Kallmann syndrome.
AB  - CONTEXT: Kallmann syndrome (KS) and CHARGE syndrome are rare heritable disorders
      in which anosmia and hypogonadotropic hypogonadism co-occur. KS is genetically
      heterogeneous, and there are at least eight genes involved in its pathogenesis,
      whereas CHARGE syndrome is caused by autosomal dominant mutations in only one
      gene, the CHD7 gene. Two independent studies showed that CHD7 mutations can also
      be found in a minority of KS patients. OBJECTIVE: We aimed to investigate whether
      CHD7 mutations can give rise to isolated KS or whether additional features of
      CHARGE syndrome always occur. DESIGN: We performed CHD7 analysis in a cohort of
      36 clinically well-characterized Dutch patients with KS but without mutations in
      KAL1 and with known status for the KS genes with incomplete penetrance, FGFR1,
      PROK2, PROKR2, and FGF8. RESULTS: We identified three heterozygous CHD7
      mutations. The CHD7-positive patients were carefully reexamined and were all
      found to have additional features of CHARGE syndrome. CONCLUSION: The yield of
      CHD7 analysis in patients with isolated KS seems very low but increases when
      additional CHARGE features are present. Therefore, we recommend performing CHD7
      analysis in KS patients who have at least two additional CHARGE features or
      semicircular canal anomalies. Identifying a CHD7 mutation has important clinical
      implications for the surveillance and genetic counseling of patients.

PMID- 22399514
TI  - Increased expression of TSH receptor by fibrocytes in thyroid-associated
      ophthalmopathy leads to chemokine production.
AB  - CONTEXT: The molecular basis for anatomically dispersed clinical manifestations
      in Graves' disease (GD) eludes our understanding. Bone marrow-derived,
      pluripotent fibrocytes represent a subset of peripheral blood mononuclear cells
      and infiltrate the orbital and thyroid tissues in GD. These cells may be involved
      in the pathogenesis of thyroid-associated ophthalmopathy (TAO). OBJECTIVE: The
      objective of the study was to quantify fibrocyte display of functional cell
      surface TSH receptor (TSHR), identify the profile of chemokines they express
      after TSHR activation, and determine whether circulating TSHR(+) peripheral blood
      fibrocytes are more frequent in situ in patients with TAO.
      DESIGN/SETTING/PARTICIPANTS: Using a newly developed technique, fibrocytes were
      directly identified in peripheral blood from 31 patients with TAO and 19 healthy
      subjects receiving care at a multidisciplinary academic center. MAIN OUTCOME
      MEASURES: The frequency in situ of fibrocytes (collagen 1(+), CD45(+), CD34(+),
      CD14(+), CD86(+) peripheral blood mononuclear cells) was assessed by
      multiparameter flow cytometry and correlated to clinical disease activity and
      smoking status. Levels of TSHR-displaying fibrocytes and their response to TSH
      and TSHR-activating antibody, M22, were measured by flow cytometry, Luminex, and
      real-time PCR. RESULTS: The levels of TSHR expression by fibrocytes are
      substantially higher than those found in orbital fibroblasts. Moreover, the
      frequency of TSHR(+) fibrocytes in patients with TAO was greater than that in
      healthy subjects in situ. Their abundance is not influenced by disease activity
      or smoking history. These cells produce high levels of several cytokines and
      chemokines including IL-8, regulated upon activation, normal T cell expressed and
      secreted, and monocyte chemoattractant protein-1 when treated with TSH or M22.
      TSH induces IL-8 production at the pretranslational level. This induced cytokine
      can be detected in intact fibrocytes ex vivo. CONCLUSIONS: Frequency of
      circulating TSHR(+) fibrocytes is markedly increased in patients with TAO, and
      they express proinflammatory chemokines in response to TSH. Because they
      infiltrate both orbit and thyroid in GD, they may represent the link between
      systemic immunoreactivity and organ-specific autoimmunity.

PMID- 22399516
TI  - Lipoprotein-associated phospholipase A2 (Lp-PLA2) and future risk of type 2
      diabetes: results from the Cardiovascular Health Study.
AB  - INTRODUCTION: Lipoprotein-associated phospholipase A2 (Lp-PLA(2)) has been
      consistently associated with cardiovascular disease (CVD) risk factors and
      predictive of CVD outcomes; furthermore, it is consistently higher among type 2
      diabetics than nondiabetics. However, the relationships of circulating Lp-PLA(2)
      mass and activity with incident type 2 diabetes mellitus have not been examined.
      Therefore, the purpose of this study was to determine the association of Lp
      PLA(2) mass and activity with type 2 diabetes among older adults. METHODS: We
      conducted analyses of Lp-PLA(2) and prevalent and incident diabetes among 5474
      men and women from the Cardiovascular Health Study (1989-2007). Lp-PLA(2) mass
      and activity were measured in baseline plasma. Diabetes status was ascertained
      annually with medication inventories and repeated blood glucose measurements.
      Generalized linear and Cox proportional hazards models were used to adjust for
      confounding factors including body mass index and inflammation. RESULTS: At
      baseline, the top two quintiles of Lp-PLA(2) activity were significantly
      associated with prevalent type 2 diabetes with a multivariable relative risk =
      1.35 [95% confidence interval (CI) = 1.11-1.63] for quintile 4, and relative risk
      = 1.33 (95% CI = 1.07-1.66) for quintile 5. Among participants free of diabetes
      at baseline, we found a significant positive association with both the
      homeostatic model assessment for insulin resistance and beta-cell function per SD
      increase in Lp-PLA(2) activity (P values for both <0.01). In prospective
      analyses, the risk of incident type 2 diabetes was significantly higher among
      those in the highest quintile of Lp-PLA(2) activity [multivariable hazard ratio =
      1.45 (95% CI = 1.01-2.07)] compared with the lowest quintile. Lp-PLA(2) mass was
      not significantly associated with incident type 2 diabetes. DISCUSSION: Lp-PLA(2)
      activity is positively associated with insulin resistance and predicts incident
      type 2 diabetes among older adults independent of multiple factors associated
      with diabetes pathogenesis.

PMID- 22399517
TI  - Increased vascular inflammation in early menopausal women is associated with hot
      flush severity.
AB  - CONTEXT: Menopause has been related to an increased atherosclerotic risk.
      Presence and severity of hot flushes in menopausal women have been associated
      with impaired endothelial function and advanced subclinical atherosclerosis.
      OBJECTIVE: The objective of the study was to evaluate the effect of menopausal
      transition on vascular inflammation indices and investigate the association of
      hot flush severity with these indices in early menopausal women. DESIGN, SETTING,
      AND PARTICIPANTS: This was a cross-sectional study that included 120 early
      menopausal women (age range 42-55 yr, <3 yr in menopause) recruited from the
      menopause outpatient clinic of an academic hospital and 24 age-matched
      premenopausal women (controls). MAIN OUTCOMES: Serum high-sensitivity C-reactive
      protein, P-selectin, and soluble CD40 ligand (sCD40L) levels were measured.
      RESULTS: P-selectin and sCD40L were increased in early menopausal compared with
      control women (P = 0.006 and P = 0.02 respectively), whereas high-sensitivity C
      reactive protein levels did not differ (P = 0.4) between the groups. Hot flush
      severity was the most important independent predictor of P-selectin levels (P =
      0.011) in early menopausal women. Women with moderate/severe/very severe hot
      flushes had increased P-selectin compared with women with no/mild hot flushes or
      controls (P < 0.05 for both). The sCD40L levels were also higher in menopausal
      women with moderate/severe/very severe hot flushes compared with controls (P =
      0.03) but did not differ significantly compared with women with no/mild hot
      flushes (P = 0.2). CONCLUSIONS: Increased indices of vascular inflammation in
      early menopausal compared with age-matched premenopausal women may indicate a
      higher atherosclerotic risk. Increased severity of hot flushes was associated
      with adverse changes in vascular inflammation, further supporting the emerging
      role of hot flushes in cardiovascular prognosis in these women.

PMID- 22399518
TI  - Impact of mifepristone, a glucocorticoid/progesterone antagonist, on HDL
      cholesterol, HDL particle concentration, and HDL function.
AB  - CONTEXT: Mifepristone is a glucocorticoid and progestin antagonist under
      investigation for the treatment of Cushing's syndrome. Mifepristone decreases
      high-density lipoprotein (HDL) cholesterol (HDL-C) levels in treated patients,
      but the clinical significance of this is unclear because recent studies suggest
      that functional properties of HDL predict cardiovascular disease status better
      than does HDL-C concentration. OBJECTIVE: The aim of the study was to
      characterize the impact of mifepristone administration on HDL particle
      concentration and function. DESIGN AND SETTING: We conducted a double-blind,
      randomized, placebo-controlled trial at a single-site, clinical research center.
      PARTICIPANTS: Thirty healthy postmenopausal female volunteers participated in the
      study. INTERVENTION: Individuals were randomized to receive daily oral
      mifepristone (600 mg) or placebo for 6 wk. MAIN OUTCOME MEASURES: We measured HDL
      C, serum HDL particle concentration, and HDL-mediated cholesterol efflux by
      treatment group. RESULTS: As expected, ACTH, cortisol, estradiol, and
      testosterone levels increased in the mifepristone group. Mifepristone treatment
      decreased HDL-C and HDL particle concentration by 26 and 25%, respectively, but
      did not alter pre-beta HDL concentration. In contrast, the serum HDL-mediated
      cholesterol efflux decreased with mifepristone treatment by only 12%, resulting
      in an effective increase of the efflux capacity per HDL particle. No changes were
      observed in cholesterol ester transfer protein or lecithin:cholesterol
      acyltransferase activity. CONCLUSIONS: Treatment with mifepristone reduced HDL-C,
      HDL particle concentration, and serum HDL cholesterol efflux in postmenopausal
      women. However, on a per particle basis, the efflux capacity of serum HDL
      increased. These observations support the concept that a decrease in HDL-C may
      not represent proportional impairment of HDL function.

PMID- 22399519
TI  - Down-regulation of the miR-25 and miR-30d contributes to the development of
      anaplastic thyroid carcinoma targeting the polycomb protein EZH2.
AB  - CONTEXT: We have previously demonstrated that a set of micro-RNA (miRNA) is
      significantly down-regulated in anaplastic thyroid carcinomas with respect to
      normal thyroid tissues and to differentiated thyroid carcinomas. OBJECTIVE: The
      objective was to evaluate the role of two of these down-regulated miRNA, miR-25
      and miR-30d, in thyroid carcinogenesis. DESIGN: miR-25 and miR-30d expression was
      restored in the ACT-1, 8505c, and FRO anaplastic thyroid cell lines, and their
      effects on cell proliferation, migration, and target expression were evaluated.
      RESULTS: We report that miR-25 and miR-30d target the polycomb protein enhancer
      of zeste 2 (EZH2) that has oncogenic activity and is drastically up-regulated in
      anaplastic thyroid carcinomas but not in the differentiated ones. Ectopic
      expression of miR-25 and miR-30d inhibited proliferation and colony formation of
      anaplastic thyroid carcinoma cells by inducing G2/M-phase cell-cycle arrest.
      Finally, we found an inverse correlation between the expression of these miRNA
      and the EZH2 protein levels in anaplastic thyroid carcinomas, suggesting a
      critical role of these miRNA in regulating EZH2 expression also in vivo.
      CONCLUSION: The down-regulation of miR-25 and miR-30d could contribute to the
      process of thyroid cancer progression, leading to the development of anaplastic
      carcinomas targeting EZH2 mRNA.

PMID- 22399520
TI  - Microchimerism and endocrine disorders.
AB  - CONTEXT: The term "microchimerism" indicates the coexistence, in the same
      organism, of genetically distinct populations of cells derived from two different
      individuals. The passage of cells from the fetus to the mother is called fetal
      cell microchimerism, whereas that occurring from the mother to the fetus is named
      maternal cell microchimerism. Microchimeric cells can persist in blood and
      tissues for decades. EVIDENCE ACQUISITION: A literature search through the U.S.
      National Library of Medicine was used to identify and review studies on maternal
      and fetal microchimerism, focusing on endocrine diseases. EVIDENCE SYNTHESIS:
      According to the majority of reports, fetal cell microchimerism seems to have a
      detrimental role in autoimmune diseases and a positive effect on tumor burden in
      most human cancers studied. In autoimmune thyroid diseases, fetal microchimeric
      cells (fmcs) have been found to be significantly more represented within the
      thyroid gland of women with Hashimoto's thyroiditis and Graves' disease compared
      to those without thyroid autoimmunity, suggesting a pathogenic role. In thyroid
      cancer tissues, fmcs have been found to be present at higher levels than in
      contralateral normal tissues and have been shown to differentiate into epithelial
      and hematopoietic cells. Microchimeric cells with hematopoietic differentiation
      could have a role in destroying the tumor, whereas epithelial cells are believed
      to participate in the repairing processes. At the peripheral level, circulating
      fmcs were less frequently detected in patients with thyroid cancer than in
      healthy individuals, consistent with data obtained for breast cancer and other
      solid and hematological malignancies, indicating a protective role against cancer
      development. Finally, type 1 diabetes has been mostly related to maternal cell
      microchimerism. Indeed, the levels of circulating maternal cells were higher in
      type 1 diabetes patients than in controls. At the pancreas level, female beta
      cells were identified and hypothesized to be targets of autoimmunity or to
      regenerate diseased tissues.

PMID- 22399521
TI  - Effect of renal function on skeletal health in primary hyperparathyroidism.
AB  - CONTEXT: Current guidelines recommend parathyroidectomy in patients with primary
      hyperparathyroidism (PHPT) who have an estimated glomerular filtration rate
      (eGFR) less than 60 ml/min per 1.73 m(2). It is unclear, however, whether values
      below this threshold of renal impairment affect bone and mineral metabolism in
      PHPT. OBJECTIVE: The purpose of this study was to assess the effect of renal
      function on skeletal health in PHPT. DESIGN: This is a retrospective analysis of
      PHPT patients with (eGFR < 60 ml/min per 1.73 m(2)) and without chronic kidney
      disease (CKD) from our previously described PHPT cohort recruited from 1984 to
      1991. SETTING: The study was conducted in a university hospital metabolic bone
      unit. PARTICIPANTS: One hundred thirty-eight women and men with PHPT were
      studied. OUTCOME MEASURES: We assessed bone mineral density (BMD) by dual-energy
      x-ray absorptiometry; quantitative histomorphometric indices from transiliac bone
      biopsies; and biochemical markers of mineral metabolism. RESULTS: Although there
      was no difference in serum or urinary calcium or PTH level, calcitriol levels
      were lower and phosphate levels higher in patients with CKD. BMD adjusted for
      weight did not differ at any site between groups. Histomorphometric analysis (n =
      30 of 138) revealed a 45% greater eroded surface in those with CKD (P = 0.02).
      Eroded surface negatively correlated with eGFR (r = -0.46, P = 0.02) and
      phosphate (r = -0.48, P = 0.02) and positively correlated with serum calcium
      level (r = 0.51, P = 0.009) but not with PTH, alkaline phosphatase, vitamin D
      metabolites, or urinary calcium excretion. CONCLUSION: Although cardinal
      biochemical indices (such as calcium and PTH) and BMD do not differ in PHPT
      patients with an eGFR below 60 ml/min per 1.73 m(2), these patients have higher
      phosphate and histomorphometric evidence of altered bone remodeling compared with
      those without CKD.

PMID- 22399522
TI  - Microbial composition and in vitro fermentation patterns of human milk
      oligosaccharides and prebiotics differ between formula-fed and sow-reared
      piglets.
AB  - The microbial composition and in vitro fermentation characteristics of human milk
      oligosaccharides (HMO), lacto-N-neotetraose (LNnT), a 2:1 mixture of polydextrose
      (PDX) and galactooligosaccharides (GOS), and short-chain fructooligosaccharides
      (scFOS) by pooled ascending colonic microbiota from 9- and 17-d-old formula-fed
      (FF) and sow-reared (SR) piglets were assessed. pH change and gas, SCFA, and
      lactate production were determined after 0, 2, 4, 8, and 12 h of incubation. In
      most donor groups, the pH change was greater for scFOS fermentation and lower for
      PDX/GOS than for other substrates. LNnT fermentation produced larger amounts of
      gas, total SCFA, acetate, and butyrate than did the other substrates, whereas HMO
      and scFOS produced higher amounts of propionate and lactate, respectively. In
      general, pH change, total SCFA, acetate, and propionate production were greater
      in pooled inoculum from FF and 9-d-old piglets, whereas SR-derived inoculum
      produced higher amounts of butyrate and lactate after 4 h fermentation. Gut
      microbiota were assessed by 16S ribosomal RNA V3 gene denaturing gradient gel
      electrophoresis analysis and real-time qPCR. Microbial structures differed among
      the 4 groups before fermentation, with higher counts of Bifidobacterium in SR
      piglets and higher counts of Clostridium cluster IV, XIVa, and Bacteroides
      vulgatus in FF piglets. Lactobacillus counts were higher in 9-d-old piglets than
      in 17-d-old piglets, regardless of diet. Bifidobacterium, Bacteroides, and
      clostridial species increased after 8 and 12 h fermentation on most substrates.
      In summary, piglet diet and age affect gut microbiota, leading to different
      fermentation patterns. HMO have potential prebiotic effects due to their effects
      on SCFA production and microbial modulation.

PMID- 22399523
TI  - Vitamin A deficiency induces fluid hyposecretion from the airway submucosal
      glands of mice.
AB  - Vitamin A deficiency (VAD) alters the phenotype of airway epithelium and
      attenuates the epithelial defense system, and many studies have reported the
      association of VAD with respiratory disease. In this study, we investigated
      changes in submucosal glands (SMG) in a mouse model of VAD. C57BL/6 mice were fed
      a vitamin A-devoid diet and the others were fed a control diet (1.2 mg
      retinol/kg). The areas of serous and mucous cells of SMG were measured in 4-, 8-,
      and 20-wk-old male mice. The volume and lysozyme concentration of glandular
      secretions were also measured. The 2 groups did not differ in body weight or
      general morbidity at 3-10 wk of age, although serum retinol concentrations were
      greater in the control mice than in the VAD mice after 4 wk. Upon histological
      evaluation, we found that the areal ratio of serous cells:total SMG cells was
      significantly lower after 8 wk in the VAD mice compared with the control mice,
      although the total area of SMG did not differ between groups throughout the 20-wk
      experiment. The number of secretory bubbles did not differ between the groups,
      but total secretion volume was reduced by 35% in 8-wk-old VAD mice compared with
      controls. Furthermore, the concentration of lysozyme in secretions from 8-wk-old
      VAD mice was also less than in controls, compounding the effect of diminished
      secretion volume. In this study, we found serous cell hypotrophy/hypoplasia and
      dysfunction in VAD mice, which may contribute to the susceptibility to airway
      infection linked to VAD.

PMID- 22399524
TI  - Genistein prevents hyperglycemia-induced monocyte adhesion to human aortic
      endothelial cells through preservation of the cAMP signaling pathway and
      ameliorates vascular inflammation in obese diabetic mice.
AB  - Hyperglycemia-induced vascular inflammation resulting in the enhanced monocyte
      endothelial cell (EC) interaction is the key event in the pathogenesis of
      atherosclerosis in diabetes. Here, we investigated the effect of isoflavone
      genistein on hyperglycemia-stimulated vascular inflammation. Human aortic EC
      (HAEC) were pretreated with genistein before the addition of high glucose (HG; 25
      mmol/L) for 48 h. Genistein at a physiological concentration (0.1 MUmol/L)
      significantly inhibited HG-induced adhesion of monocytes to HAEC and suppressed
      endothelial production of monocyte chemotactic protein-1 (MCP-1) and IL-8.
      Inhibition of adenylate cyclase or protein kinase A (PKA) significantly
      attenuated the antiadhesion effect of genistein. Consistently, genistein improved
      HG-impaired intracellular cAMP production and PKA activity in HAEC. Six-week-old
      diabetic db/db mice were untreated (db/db) or treated with a diet containing 1 g
      genistein/kg diet (db/db+G) for 8 wk. Their nondiabetic db/+ mice were used as
      normal controls. Circulating concentrations of MCP-1/JE and KC were significantly
      greater, whereas IL-10 concentrations were lower in db/db mice than those in
      normal mice. Dietary supplementation of genistein did not normalize but
      significantly suppressed the elevated serum concentrations of MCP-1/JE from 286
      +/- 30 ng/L to 181 +/- 35 ng/L and KC from 321 +/- 21 ng/L to 232 +/- 20 ng/L
      while increasing that of IL-10 from 35 +/- 4 ng/L to 346 +/- 35 ng/L in db/db+G
      mice. Further, genistein treatment suppressed diabetes-induced adhesion of
      monocytes to EC by 87% and endothelial secretion of adhesion molecules. We
      conclude that genistein improves diabetes-caused vascular inflammation, which may
      be mediated through promoting the cAMP/PKA pathway.

PMID- 22399525
TI  - Xanthones in mangosteen juice are absorbed and partially conjugated by healthy
      adults.
AB  - The proposed health-promoting effects of the pericarp from mangosteen fruit have
      been attributed to a family of polyphenols referred to as xanthones. The purpose
      of this study was to determine the bioavailability of xanthones from 100%
      mangosteen juice in healthy adult participants (n = 10). Pericarp particles
      accounted for 1% of the mass and 99% of the xanthone concentration in the juice.
      The juice provided 5.3 +/- 0.1 mmol/L total xanthones with alpha-mangostin,
      garcinones (C, D, and E), gamma-mangostin, gartanins, and other identified
      xanthones accounting for 58, 2, 6, 4, and 5%, respectively. Participants ingested
      60 mL mangosteen juice with a high-fat breakfast. Free and conjugated
      (glucuronidated/sulfated) xanthones were detected in serum and urine. There was
      marked variation in the AUC (762-4030 nmol/L * h), maximum concentration (113 +/-
      107 nmol/L), and time to maximum concentration (3.7 +/- 2.4 h) for alpha
      mangostin in sera during the 24-h collection. Similarly, xanthones in 24-h urine
      ranged from 0.9 to 11.1 MUmol and accounted for 2.0 +/- 0.3% (range 0.3-3.4%) of
      the ingested dose. There were no significant differences between female and male
      participants in mean pharmacokinetic values of alpha-mangostin in serum and
      urinary xanthones. Only 15.4 +/- 0.7% of total xanthones in pericarp particles in
      the juice partitioned into mixed micelles during in vitro digestion. These
      results show that xanthones in mangosteen juice are absorbed when ingested along
      with a high-fat meal, although release of xanthones from pericarp particles
      during digestion may be limited.

PMID- 22399526
TI  - High circulating folate and vitamin B-12 concentrations in women during pregnancy
      are associated with increased prevalence of atopic dermatitis in their offspring.
AB  - Recent studies suggest that in utero exposure of methyl donors influences
      programming of the fetal immune system in favor of development of allergic
      disease. The aim of this study was to assess whether the MTHFR C677T
      polymorphism, folic acid supplementation, and circulating folate and vitamin B-12
      concentrations during pregnancy were associated with wheezing, shortness of
      breath, and atopic dermatitis in offspring. The study was a population-based
      birth cohort from fetal life until 48 mo (n = 8742). The use of folic acid
      supplementation during pregnancy was assessed by questionnaire. Plasma folate and
      serum vitamin B-12 concentrations and the MTHFR C677T polymorphism were available
      from blood collected in early pregnancy. Atopic dermatitis, wheezing, and
      shortness of breath in the offspring were assessed by parental-derived
      questionnaires at 12, 24, 36, and 48 mo. Maternal folate >16.2 nmol/L and vitamin
      B-12 >178 pmol/L were positively associated with the development of atopic
      dermatitis [adjusted OR: 1.18 (95% CI: 1.05-1.33) and adjusted OR: 1.30 (95% CI:
      1.06-1.60) for the highest quartiles of folate and vitamin B-12 concentrations,
      respectively] but not with wheezing and shortness of breath. Maternal MTHFR C677T
      polymorphism and folic acid supplementation were not associated with wheezing,
      shortness of breath, and atopic dermatitis. No interactions were found by age,
      family history of atopy, folic acid supplementation, MTHFR C677T polymorphism, or
      maternal smoking (P-interaction > 0.10). High folate and vitamin B-12 levels
      during pregnancy are associated with increased prevalence of atopic dermatitis in
      the offspring. Potential risks of high folate and vitamin B-12 concentrations on
      allergic outcomes should be evaluated when discussing mandatory fortification
      programs.

PMID- 22399527
TI  - Genome-wide screen for metabolic syndrome susceptibility Loci reveals strong
      lipid gene contribution but no evidence for common genetic basis for clustering
      of metabolic syndrome traits.
AB  - BACKGROUND: Genome-wide association (GWA) studies have identified several
      susceptibility loci for metabolic syndrome (MetS) component traits, but have had
      variable success in identifying susceptibility loci to the syndrome as an entity.
      We conducted a GWA study on MetS and its component traits in 4 Finnish cohorts
      consisting of 2637 MetS cases and 7927 controls, both free of diabetes, and
      followed the top loci in an independent sample with transcriptome and nuclear
      magnetic resonance-based metabonomics data. Furthermore, we tested for loci
      associated with multiple MetS component traits using factor analysis, and built a
      genetic risk score for MetS. METHODS AND RESULTS: A previously known lipid locus,
      APOA1/C3/A4/A5 gene cluster region (SNP rs964184), was associated with MetS in
      all 4 study samples (P=7.23*10(-9) in meta-analysis). The association was further
      supported by serum metabolite analysis, where rs964184 was associated with
      various very low density lipoprotein, triglyceride, and high-density lipoprotein
      metabolites (P=0.024-1.88*10(-5)). Twenty-two previously identified
      susceptibility loci for individual MetS component traits were replicated in our
      GWA and factor analysis. Most of these were associated with lipid phenotypes, and
      none with 2 or more uncorrelated MetS components. A genetic risk score,
      calculated as the number of risk alleles in loci associated with individual MetS
      traits, was strongly associated with MetS status. CONCLUSIONS: Our findings
      suggest that genes from lipid metabolism pathways have the key role in the
      genetic background of MetS. We found little evidence for pleiotropy linking
      dyslipidemia and obesity to the other MetS component traits, such as hypertension
      and glucose intolerance.

PMID- 22399529
TI  - Anaemia and iron deficiency in cardiac patients: what do nurses and allied
      professionals know?
AB  - BACKGROUND: Cardiac nurses and allied professionals often take care of patients
      who also have anaemia or iron deficiency. To deliver optimal care, professionals
      should be knowledgeable about the prevalence, diagnosis, pathophysiology, and
      therapeutic management of these conditions. We therefore set out a survey to get
      a first impression on the current knowledge of nurses and allied professionals on
      anaemia and iron deficiency. METHOD: A questionnaire was designed for this study
      by the Undertaking Nursing Interventions Throughout Europe (UNITE) Study Group.
      Data were collected from 125 cardiovascular nurses and allied professionals
      visiting the 11th Annual Spring Meeting of the Council on Cardiovascular Nursing
      and Allied Professionals of the European Society of Cardiology. RESULTS: Most
      respondents had general knowledge on the definition of anaemia and iron
      deficiency and 54% of the respondents rated anaemia and iron deficiency as
      important when evaluating a cardiac patient. Specific knowledge regarding anaemia
      and more prominently of iron deficiency was not optimal. CONCLUSION: Although
      cardiac nurses and allied professionals have basic knowledge of anaemia and iron
      deficiency, they would benefit from additional knowledge and skills to optimally
      deliver patient care.

PMID- 22399534
TI  - How accurate are 3 risk prediction models in US women?

PMID- 22399537
TI  - Practice and research: seeking common ground to benefit people.

PMID- 22399538
TI  - Towards an integrated community approach of overweight prevention: the
      experiences of practitioners and policymakers.
AB  - BACKGROUND: Fighting overweight effectively asks for a community-based coherent
      integrated approach. The first step in improving the local prevention of
      overweight is to retrieve practice-based information on the interventions used
      and the experiences of practitioners. OBJECTIVES: A variety of practitioners and
      policymakers in three different cities in The Netherlands were interviewed to
      investigate: what kind of interventions are used in practice today? What is
      helpful and what does not to implement these interventions? What is needed? How
      is the collaboration between the parties involved? METHODS: Three observers
      classified all statements systematically according to the four categories from
      the implementation model by Fleuren M, Wiefferink K, Paulussen T (Determinants of
      innovation within health care organizations: literature review and Delphi study.
      Int J Qual Health Care 2004; 16: 107-123). RESULTS: In Nijmegen, 29 interventions
      for the prevention or treatment of overweight were identified for the target
      group youth and 22 for adults. In Wijchen, these were, respectively, 22 and 13
      interventions, and in Maasdriel, 24 interventions were found for youth. Most
      interventions addressed healthy eating and/or physical activity, a few paid
      attention to psychological or pedagogical aspects. Most participants were
      satisfied with the intervention(s) they used. For the question 'what does not
      work?', 61% of the answers were related to characteristics of the organization or
      social and political context of the intervention. Merely, all sectors expressed
      difficulties in involving parents. CONCLUSIONS: Many different interventions are
      applied in everyday practice within each city, but in a fragmented way. Too
      little attention is being paid to pedagogical aspects and to involving parents in
      preventing overweight.

PMID- 22399535
TI  - Comparison of the Framingham and Reynolds Risk scores for global cardiovascular
      risk prediction in the multiethnic Women's Health Initiative.
AB  - BACKGROUND: Framingham-based and Reynolds Risk scores for cardiovascular disease
      (CVD) prediction have not been directly compared in an independent validation
      cohort. METHODS AND RESULTS: We selected a case-cohort sample of the multiethnic
      Women's Health Initiative Observational Cohort, comprising 1722 cases of major
      CVD (752 myocardial infarctions, 754 ischemic strokes, and 216 other CVD deaths)
      and a random subcohort of 1994 women without prior CVD. We estimated risk using
      the Adult Treatment Panel III (ATP-III) score, the Reynolds Risk Score, and the
      Framingham CVD model, reweighting to reflect cohort frequencies. Predicted 10
      year risk varied widely between models, with >=10% risk in 6%, 10%, and 41% of
      women with the ATP-III, Reynolds, and Framingham CVD models, respectively.
      Calibration was adequate for the Reynolds model, but the ATP-III and Framingham
      CVD models overestimated risk for coronary heart disease and major CVD,
      respectively. After recalibration, the Reynolds model demonstrated improved
      discrimination over the ATP-III model through a higher c statistic (0.765 versus
      0.757; P=0.03), positive net reclassification improvement (NRI; 4.9%; P=0.02),
      and positive integrated discrimination improvement (4.1%; P<0.0001) overall,
      excluding diabetics (NRI=4.2%; P=0.01), and in white (NRI=4.3%; P=0.04) and black
      (NRI=11.4%; P=0.13) women. The Reynolds (NRI=12.9%; P<0.0001) and ATP-III
      (NRI=5.9%; P=0.0001) models demonstrated better discrimination than the
      Framingham CVD model. CONCLUSIONS: The Reynolds Risk Score was better calibrated
      than the Framingham-based models in this large external validation cohort. The
      Reynolds score also showed improved discrimination overall and in black and white
      women. Large differences in risk estimates exist between models, with clinical
      implications for statin therapy.

PMID- 22399539
TI  - 'Healthy children in sound communities' (HCSC/gkgk)--a Dutch-German community
      based network project to counteract obesity and physical inactivity.
AB  - BACKGROUND: In 12 municipalities at the German-Dutch border an integrated
      approach of a multi-component intervention programme (physical activity,
      nutrition, public health, improvement of the physical environment) to enhance an
      active lifestyle has been implemented in 39 primary schools for a 4-year
      longitudinal intervention and evaluation study. OBJECTIVE: A weekly lesson plan,
      including 3 hours of health enhanced physical education and two additional hours
      of physical activities offered by sport clubs to balance motor deficits and to
      reduce overweight and obesity was implemented. Furthermore, another hour of cross
      curricular education of health and nutrition education is part of the school
      curriculum. To achieve 60 to 90 minutes of daily physical activities for 6- to 10
      year-old pupils active commuting to school has become a part of school life.
      METHODS: A physical fitness and motor development test is applied each school
      year including BMI measurements as a part of a socio-ecological concept.
      Intrapersonal developments of the pupils are measured by different questionnaires
      focusing on the individual social context of physical activity, nutrition habits
      and time allocation for electronic media. RESULTS: Original values of Motor
      Ability tests show significant increase in endurance, coordination, velocity and
      force tasks. Also first changes for BMI distribution are explored in only one
      year intervention. CONCLUSION: First results indicate the possibility to
      counteract obesity and to increase levels of physical fitness and motor
      development by a multi-component progamme and a multi-sector approach of
      intervention. The longitudinal design of the study allows having a look on long
      term effects.

PMID- 22399540
TI  - How science thinks and practice acts: bridging the gap in weight management
      interventions for adolescents.
AB  - BACKGROUND: Adolescent obesity calls for evidence-based treatment approaches
      given its long-term physical and psychosocial consequences. However, research
      shows there are many problems in the translation of scientific evidence into
      practice. OBJECTIVE: The aim of this study was to develop science- and practice
      based recommendations for the planning of future adolescent weight management
      interventions. METHODS: We performed (i) literature reviews on intervention
      studies targeting treatment of obesity in adolescents and Dutch clinical
      guidelines for obesity as well as practice-based documents and grey literature on
      treating obesity and delivering health programs for adolescents and (ii) semi
      structured interviews with eight clinicians and four non-clinicians working in
      obesity treatment, management and prevention to explore perspectives on treating
      adolescent obesity and using evidence in practice. RESULTS: After merging the
      results from the literature reviews and interviews, four issues emerged: (i)
      little reporting on theoretical models used in intervention studies, Dutch
      clinical guidelines and semi-structured interviews; (ii) inconsistency on age
      specific considerations for treating obesity in adolescents in intervention
      studies and Dutch clinical guidelines; (iii) inconsistency on addressing the
      social nature of obesity in intervention studies and Dutch clinical guidelines
      and (iv) how professional responsibility should be divided is unclear from
      intervention studies, Dutch clinical guidelines and semi-structured interviews.
      CONCLUSIONS: Joined action of science and practice is required for future
      interventions. Future interventions should include topics relevant to the stage
      of adolescence and give greater focus to the complex social nature of obesity.
      Lastly, practitioners can generate more practice-based evidence by starting their
      own practice-based research.

PMID- 22399541
TI  - Bridging the gap between public health and primary care in prevention of
      cardiometabolic diseases; background of and experiences with the Prevention
      Consultation in The Netherlands.
AB  - BACKGROUND: There is an increasing need for programmatic prevention of
      cardiometabolic diseases (cardiovascular disease, type 2 diabetes and chronic
      kidney disease). Therefore, in the Netherlands, a prevention programme linked to
      primary care has been developed. This initiative was supported by the national
      professional organizations of GPs and occupational physicians as well as three
      large health foundations. OBJECTIVES: To describe and discuss the content,
      structure of and first experiences with this initiative. METHODS: Description of
      context, risk assessment tool, guideline, content of the Prevention Consultation
      and pilot studies. RESULTS: Preceding surveys revealed a need for proactive
      disease prevention, linked to primary care. An evidence-based guideline was
      developed using a validated eight-question screening list. According to the
      guideline, high-risk participants were advised to attend two consultations at the
      general practice, for completing the risk assessment and for tailored advice.
      Three pilot studies revealed that the programme was feasible and that
      (sufficient) participants with a condition requiring treatment were detected. We
      learned that with a 'passive' recruitment (with only posters and brochures),
      screening uptake is limited. A more active approach with a personal invitation
      from the GP is more effective. Both an Internet as written questionnaire should
      be available and reminders are necessary. The need for a consultation with the GP
      practice after a high-risk test result should be emphasized. The first
      consultation can be performed by a practice nurse. CONCLUSIONS: A national
      systematic screening programme for cardiometabolic diseases linked to primary
      care is feasible. The cost-effectiveness still has to be established.

PMID- 22399543
TI  - The Healthy ALLiances (HALL) framework: prerequisites for success.
AB  - BACKGROUND: Chronic conditions are on the rise worldwide, and there is
      increasingly a call for the primary care and public health sectors to join forces
      in alliances. GPs have an important role to play in such alliances. However,
      successful cooperation is not as obvious as it may seem, and the sectors are not
      used to working together. OBJECTIVE: The objective is to identify conditions and
      prerequisites for successful alliances. METHOD: Identification of conditions and
      prerequisites is mainly based on stepwise analysis and iterative developments in
      research on collaboration processes in the area of health promotion and public
      health. RESULTS: The process as a whole resulted in the framework presented in
      this paper. This so-called HALL framework identifies three clusters of factors
      that either hinder or facilitate the success of alliances: (i) institutional
      factors, (ii) personal factors of participants in the alliance and (iii) factors
      relating to the organization of the alliance. The institutional and personal
      factors 'stick' to the stakeholders and are brought into the alliance. The third
      group refers to the lessons learned from dealing with the first two
      characteristics to make the alliance successful. CONCLUSION: Partners in
      alliances bring in personal attributes and institutional characteristics that can
      form obstacles to successful alliances, but, when they are addressed in a
      flexible and positive way, obstacles can be turned in contributory factors,
      leading to many potential benefits, such as collaborative learning and
      innovation.

PMID- 22399542
TI  - Primary prevention of type 2 diabetes: integrative public health and primary care
      opportunities, challenges and strategies.
AB  - Type 2 diabetes imposes a large and growing burden on the public's health. This
      burden, combined with the growing evidence for primary prevention from randomized
      controlled trials of structured lifestyle programs leads to recommendations to
      include caloric reduction, increased physical activity and specific assistance to
      patients in problem solving to achieve modest weight loss as well as
      pharmacotherapy. These recommendations demand exploration of new ways to
      implement such primary prevention strategies through more integrated community
      organization, medical practice and policy. The US experience with control of
      tobacco use and high blood pressure offers valuable lessons for policy, such as
      taxation on products, and for practice in a variety of settings, such as
      coordination of referrals for lifestyle supports. We acknowledge also some
      notable exceptions to their generalizability. This paper presents possible
      actions proposed by an expert panel, summarized in Table 1 as recommendations for
      immediate action, strategic action and research. The collaboration of primary
      care and public health systems will be required to make many of these
      recommendations a reality. This paper also provides information on the progress
      made in recent years by the Division of Diabetes Translation at the US Centers
      for Disease Control and Prevention (CDC) to implement or facilitate such
      integration of primary care and public health for primary prevention.

PMID- 22399544
TI  - The implementation of the Counterweight Programme in Scotland, UK.
AB  - BACKGROUND: The Counterweight Programme is a proven model for the management of
      obesity in the UK, evaluated over 5 years (2000-05) and demonstrating clinical
      and cost effectiveness. The Scottish Government commissioned three phases of
      Counterweight implementation during the period 2006-08. The first two phases
      linked the Counterweight Programme to a primary care cardiovascular disease
      prevention programme; the third phase was commissioned independent of other
      interventions. Aim. To assess the implementation of the Counterweight Programme
      in 13 Health Boards in Scotland and compare 12-month outcomes with published
      Counterweight data. METHODS: Patients with a body mass index (BMI) >= 30 kg/m(2)
      or BMI >= 28 kg/m(2) with at least one co-morbidity were screened for the
      Counterweight Programme. Patients were asked to attend nine structured
      appointments with a trained Counterweight Programme practitioner over 12 months.
      RESULTS: Six thousand seven hundred and fifteen patients from 184 general
      practices, 16 pharmacies and one centralized community-based service in 13 Health
      Boards, with a mean BMI of 37 kg/m(2) were enrolled in the Counterweight
      Programme. Twenty-six per cent had a BMI >= 40 kg/m(2). Attendance for patients
      at 3, 6 and 12 months follow-up was 55%, 37% and 28%. Of those who attended at 12
      months, 35.2% had maintained a weight loss of >=5% compared to 30.7% in the
      original evaluation. CONCLUSIONS: Evaluation of the Counterweight Programme in
      Scotland demonstrated consistency in characteristics of patients enrolled into
      the programme. There was evidence of higher loss to follow-up in a population not
      routinely engaging with primary care but evidence of greater weight losses among
      those who attended.

PMID- 22399545
TI  - Translating the SLIM diabetes prevention intervention into SLIMMER: implications
      for the Dutch primary health care.
AB  - All over the world, prevalence and incidence rates of type 2 diabetes mellitus
      are rising rapidly. Several trials have demonstrated that prevention by lifestyle
      intervention is (cost-) effective. This calls for translation of these trials to
      primary health care. This article gives an overview of the translation of the
      SLIM diabetes prevention intervention to a Dutch real-life setting and discusses
      the role of primary health care in implementing lifestyle intervention
      programmes. Currently, a 1-year pilot study, consisting of a dietary and physical
      activity part, performed by three GPs, three practice nurses, three dieticians
      and four physiotherapists is being conducted. The process of translating the SLIM
      lifestyle intervention to regular primary health care is measured by means of the
      process indicators: reach, acceptability, implementation integrity, applicability
      and key factors for success and failure of the intervention. Data will be derived
      from programme records, observations, focus groups and interviews. Based on these
      results, our programme will be adjusted to fit the role conception of the
      professionals and the organization structure in which they work.

PMID- 22399546
TI  - An integrated health care standard for the management and prevention of obesity
      in The Netherlands.
AB  - The Partnership Overweight Netherlands (PON) is a collaboration between 18
      partners, which are national organizations of health care providers, health
      insurance companies and patient organizations. The PON published an integrated
      health care standard for obesity in November 2010. The integrated health care
      standard for obesity involves strategies for diagnosis and early detection of
      high-risk individuals as well as appropriate combined lifestyle interventions for
      those who are overweight and obese and, when appropriate, additional medical
      therapies. The PON works towards a standard that transcends traditional
      boundaries of conventional health care systems and health care professions but,
      instead, focuses on competences of groups of health professionals who organize
      care from a patient-oriented perspective.

PMID- 22399547
TI  - Academic collaborative centres for health promotion in the Netherlands: building
      bridges between research, policy and practice.
AB  - A logical and promising next step for the development of an effective
      infrastructure for health promotion in the Netherlands are Academic Collaborative
      Centres (ACCs). Their aims are to bridge the gap between research, policy and
      practice; make better use of available knowledge and strengthen the evidence base
      for health promotion practice. To understand their position, they must be seen in
      light of the strong growth in health promotion in the Netherlands. Since the
      1970s, the emphasis in health promotion has shifted from simple unidimensional
      interventions to much more comprehensive and integrated programmes. Comprehensive
      research programmes, which explicitly involve actual practice and policy, are
      also thus called for. These developments are described in this article. There is
      considerable and widespread enthusiasm about the establishment of ACCs in the
      Netherlands. Experiences from the first 5 years of collaboration between
      research, policy and practice within the ACCs, however, shows research to still
      have the dominant position. The different groups of stakeholders in the public
      health infrastructure are also shown to perceive and appreciate the current
      infrastructure rather differently. These findings are similar to results found in
      the USA. The predominance of research has recently led the Netherlands
      Organization for Health Research and Development (ZonMw) to impose stricter
      criteria and guidelines for the funding of such centres. These measures are aimed
      at eliciting a shift of power from science to practice. They seem to be a
      promising contribution to bridging the gap between research, policy and practice.

PMID- 22399548
TI  - Behind the scenes of doctors' nutritional advice: the infrastructure of nutrition
      information that is used in practice.
AB  - Though this sixth Heelsum meeting has concentrated on over- and under-nutrition,
      GPs in their work look after patients with a wide range of diseases that may be
      helped by different dietary managements (van Weel C. Morbidity in family
      medicine: the potential for individual nutritional counselling, an analysis from
      the Nijmegen Continuous Morbidity Registration. Am J Clin Nutr 1997; 65 (suppl
      6): 1928s-32s). Much attention is paid to evidence from randomized controlled
      trials (RCTs). However, most of the nutrition advice by physicians has to be
      based on accumulated evidence from different sources other than Cochrane reviews
      and RCTs (Truswell AS. Levels and kinds of evidence for public-health nutrition.
      Lancet 2001; 357: 1061-2; Truswell AS. Some problems with Cochrane reviews of
      diet and chronic disease. Eur J Clin Nutr 2005; 59 (suppl 1): s150-4). This paper
      will briefly review the informational infrastructure of human nutrition, being
      regularly updated, that is in the background of doctors' advice on diets to their
      patients. The main parts of this nutrition information include: (i) recommended
      nutrient intakes/dietary reference intakes, (ii) dietary goals and guidelines,
      (iii) textbooks of human nutrition, (iv) chapters on nutrition in medical
      textbooks, (v) ABC of Nutrition, written for GPs and (vi) lastly, a new book
      about the research on diet and coronary heart disease (CHD) in the 20th century
      contains the main pieces of evidence that underlie today's nutrition guidance
      both to people at risk of CHD and for the general community.

PMID- 22399549
TI  - Attitudes toward preventive services and lifestyle: the views of primary care
      patients in Europe. the EUROPREVIEW patient study.
AB  - BACKGROUND: For preventive interventions in general practice to succeed,
      patients' points of view must be taken into account in addition to those of GPs.
      OBJECTIVE: To explore patients' views and beliefs about the importance of
      lifestyle and preventive interventions, to assess their readiness to make changes
      to their lifestyle and their willingness to receive support from GPs. METHODS:
      Cross-sectional survey conducted by EUROPREV in primary care practices in 22
      European countries. Patients were consecutively selected and interviewed from
      September 2008 to September 2009. RESULTS: Seven thousand nine hundred and forty
      seven participants, 52.2% females. Only 30.5% of risky drinkers think they need
      to change, as opposed to 64% of smokers, 73.5% of patients with unhealthy eating
      habits and 73% with lack of physical activity. Risky drinkers reported that GPs
      initiated a discussion on alcohol consumption less often (42%) than on smoking
      (63%), eating habits (59%) or physical activity (55%). Seventy-five per cent, 66%
      and 63% of patients without hypertension, diabetes or hypercholesterolaemia,
      respectively, think blood pressure, blood sugar and serum cholesterol should be
      checked yearly. Women (80%) think they should be screened with the cervical smear
      test and 72.8% of women aged 30-49 years with mammography, yearly or every 2
      years. CONCLUSIONS: A high proportion of patients attending primary care with
      unhealthy lifestyles (especially risky drinkers) do not perceive the need to
      change their habits, and about half the patients reported not having had any
      discussion on healthy lifestyles with their GPs. Patients overestimate their need
      to be screened for cardiovascular risk factors and for cancer.

PMID- 22399550
TI  - A local consensus process making use of focus groups to enhance the
      implementation of a national integrated health care standard on obesity care.
AB  - BACKGROUND: Recent guidelines on obesity management promote integrated care.
      There is little knowledge about local opportunities and barriers, faced by health
      care professionals and patients, that affect implementation of an integrated
      national health care standard in a local setting. Our aim is to understand
      experiences and expectations of health care professionals and patients as part of
      the local implementation process. METHODS: Eight focus groups and two interviews
      have been conducted among 24 patients (60+) and 29 professionals from seven
      different care disciplines. RESULTS: Both patients and professionals have
      identified serious barriers to implement the national standard: older adults do
      not feel taken seriously and experience lacking support from professionals.
      Professionals give contradictory advice and recommendations do not match needs of
      older adults. Professionals actually feel reluctant to discuss weight-related
      topics due to several reasons: they do not consider obesity being a chronic
      disease, lack of qualifications to support self-management and perceived lack of
      awareness and motivation among patients. CONCLUSION: Focus groups have proven
      their value to ascertain the opportunities and barriers older adults and
      professionals foresee while improving obesity care in order to meet the standards
      as required in a national guideline. Our research provides an emerging picture of
      health care professionals and patients having contradictory views and
      expectations about 'the others' role and their notions on the capability to
      intervene on patient's weight problems. Without this emerging picture, we would
      have missed important information on barriers to overcome. The likelihood of
      successful implementation would then have been small.

PMID- 22399552
TI  - Engaging municipalities in community capacity building for childhood obesity
      control in urban settings.
AB  - BACKGROUND: Reducing rates of child obesity requires an approach that transcends
      the medicalization of overweight. Family practice doctors and public health
      professionals need to work with other sectors to establish comprehensive
      approaches to obesity reduction. OBJECTIVES: This study compares the approaches
      of three cities with different health and political systems (Lisbon, London and
      New York City) to promoting effective action to decrease child obesity. METHODS:
      Using a comparative case study approach, participant observers in three
      intersectoral municipal collaborative on child obesity describe their challenges
      and accomplishments. RESULTS: Municipal governments made child obesity a policy
      priority and coordinate efforts in different sectors. Public health provided
      relevant information on population characteristics and scientific evidence for
      decision-making, family practice monitored children's growth and assisted
      families to adopt healthy behaviors. These sectors, together with university
      based researchers, also played an advocacy role, addressing inequalities,
      alerting the public and policy makers about damaging products or risky
      situations, and regulating private interests that threaten well-being, e.g., the
      food and beverage industry that promotes unhealthy products. Local, national and
      global networks of health providers, municipal agencies and researchers have
      helped to diagnose problems, coordinate action across sectors and levels, share
      and evaluate successes and failures, translate evidence into practice and promote
      social cohesion. CONCLUSIONS: These cities have developed common approaches and
      face similar challenges in reducing high rates of child obesity, suggesting that
      it may be possible for cities in different parts of the world to learn from each
      other and thus accelerate progress.

PMID- 22399553
TI  - Primary care and public health a natural alliance? The introduction of the
      guidelines for obesity and undernutrition of the Dutch College of General
      Practitioners.
AB  - The prevalence of obesity and overweight is increasing globally and forms a huge
      public health problem. On the other hand, the prevalence of malnutrition or
      undernutrition is substantial, especially in nursing homes or in the elderly at
      home. Primary care and public health are separate disciplines. But in the field
      of nutrition and other lifestyle-related interventions, there are many direct and
      indirect interfaces for over- as well as undernutrition. The Dutch College of
      General Practitioners (NHG) published the Practice Guideline Obesity in adults
      and children to lead GPs in this process and to bridge the gap with public
      health. The same applies for the recently published National Primary Care
      Cooperation Agreement Undernutrition on the collaboration of primary care workers
      to enhance awareness and early intervention in case of nutritional impairment.
      This article goes into the background as well as the content of these two NHG
      products and the implications for daily practice. An attempt is made to connect
      primary care and public health in this matter. Particularly in the case of
      obesity, a close relationship with public health is of vital importance.

PMID- 22399554
TI  - Nutrient-rich foods in relation to various measures of anthropometry.
AB  - BACKGROUND: Nutrient quality systems, for example the nutrient-rich foods (NRF)
      index, measure the nutrient quality of individual foods and may be used to assess
      the nutrient density of the overall diet. It is not yet known whether the NRF
      index is helpful in weight management. We hypothesize that a nutrient-dense diet
      is associated with a lower body weight and waist circumference. OBJECTIVE: The
      objective of the present study was to examine the association between the NRF
      index and various measures of anthropometry. METHODS: This study was carried out
      in a sample of 2044 men and 2925 women, aged >=55 years, participating in a
      community-based prospective cohort study in Rotterdam, The Netherlands. The
      NRF9.3 algorithms were used to estimate the nutrient density of the subjects'
      diets. Linear regression was used to examine the association between the NRF
      index scores and body mass index (BMI), body weight, waist circumference, wait-to
      hip ratio and waist-to-height ratio. RESULTS: Subjects with a high NRF9.3 index
      score had a lower energy intake (EI) as compared to those with low NRF9.3 index
      score. However, after adjustment for age, gender and other confounders, the
      NRF9.3 index score as well as the Nutrient Rich 9 index score were positively
      associated with BMI, body weight, waist circumference and waist-to-height ratio.
      CONCLUSIONS: Although subjects with a high NRF9.3 index score had a lower EI than
      those subjects with a low index score, their BMI, body weight, waist
      circumference and waist-to-height ratio was higher. The association between
      nutrient quality and body composition is therefore complex.

PMID- 22399555
TI  - Sarcopenia in the elderly.
AB  - Sarcopenia is the age-related loss of muscle. It leads to loss of muscle power,
      which in the end results in frailty and disability. There are numerous causes of
      sarcopenia. Treatment consists of resistance exercise and a leucine-enriched
      essential amino acid protein supplement. There is an emerging role for
      testosterone and other anabolic steroids. An activin II receptor soluble fusion
      protein is showing great potential to increase muscle mass and bone mineral
      density.

PMID- 22399557
TI  - The use of theory in research on nutrition guidance practices by primary care
      physicians from 1995 to October 2008: a review.
AB  - BACKGROUND: Theory-based interventions on nutrition guidance practices of primary
      care physicians (PCPs) are thought to be more effective than those that do not
      use theory. OBJECTIVE: To assess how often and which theoretical models of
      behaviour change are used in research on nutrition guidance practices of PCPs.
      METHOD: A review of articles published from 1995 to October 2008 (n = 111).
      RESULTS: It was found that 45% of the articles in this review included theories
      or theoretical models of behaviour change. No difference in proportion of model
      use was found with time. Model use differed between type of study. In 29% of the
      articles, the Transtheoretical Model was used. Little was found on authors' views
      on theoretical model applicability. CONCLUSIONS: Forty-five per cent of the
      articles on nutrition guidance practices of PCPs published from 1995 to October
      2008 included theories or theoretical models of behaviour change. It would be
      beneficial for nutrition behaviour change research if more researchers use
      theoretical models and report on applicability of the selected theory, to
      increase effectiveness of nutrition guidance by PCPs.

PMID- 22399556
TI  - Beliefs and attitudes to lifestyle, nutrition and physical activity: the views of
      patients in Europe.
AB  - OBJECTIVE: The aim of the EUROPREVIEW study was to explore patients' beliefs
      about the importance of lifestyle and preventive services, to assess their
      readiness to make changes in diet and physical activity and their willingness to
      receive support from GPs. METHODS: The study was done in 22 European countries,
      in 10 practices per country, with each 40 patients aged 30-70 years. The
      interview period was September 2008 to September 2009. The analysis was based on
      7947 participants (52.2% females and 47.8% males). RESULTS: More than half of the
      patients think their lifestyle is important for their health: eating habits 53%,
      physical activity 55% and normal body weight 59%. Almost half of the patients
      think they have to improve their lifestyle in terms of eating behaviour (43%),
      physical activity (48%) and body weight (48%). More than half of the patients say
      they have plans to change and two-thirds say they are confident to succeed. Two
      thirds of the patients say that they would like to receive support by their GP.
      About half of patients reported that GPs initiated a discussion about these
      topics. CONCLUSIONS: This study raises a number of health promotion and
      prevention issues of interest for primary health care providers. There is a
      discrepancy between the expectations of patients and the performance of GPs. A
      high proportion of patients who visited primary care with unhealthy lifestyles do
      not perceive the need to change and about half of the patients reported not
      having any discussion on these topics with GPs or primary care team.

PMID- 22399558
TI  - Practice-based evidence for weight management: alliance between primary care and
      public health.

PMID- 22399559
TI  - A longitudinal study of changes in noticing and treating patients' overweight by
      Dutch GPs between 1997 and 2007.
AB  - BACKGROUND: One of the stakeholders in tackling the rise and health consequences
      of overweight and obesity is the general practice physician (GP). GPs are in a
      good position to inform and give nutrition guidance to overweight patients.
      OBJECTIVE: Assessment of working mechanism of determinants of the nutrition
      guidance practice: noticing patients' overweight and guidance of treatment by GPs
      [linear analysis of structural relations (LISREL) path model] in a longitudinal
      study. METHODS: This longitudinal study measured data in 1992, 1997 and 2007. The
      1992 LISREL path model (Hiddink GJ, Hautvast J, van Woerkum CMJ, Fieren CJ, van
      t'Hof MA. Nutrition guidance by primary-care physicians: LISREL analysis improves
      understanding. Prev Med 1997; 26: 29-36.) demonstrated that 'noticing patients'
      overweight and guidance of treatment' was directly and indirectly influenced by
      predisposing factors, driving forces and perceived barriers. This article defines
      and discusses the path analysis of the 2007 data (compared with 1997). RESULTS:
      This analysis shows both similarity and differences in working mechanism of
      determinants of noticing patients' overweight and guidance of treatment between
      1997 and 2007. The backbone of the mechanism with four predisposing factors is
      the similarity. The number of driving forces and of paths through intermediary
      factors to the dependent variable constitutes the difference. CONCLUSIONS: The
      backbone of the working mechanism of determinants of the nutrition guidance
      practice: noticing patients' overweight and guidance of treatment by GPs was
      similar in 2007 and 1997. The influence of GPs task perception on noticing
      patients' overweight and guidance of treatment considerably increased in 2007
      compared to 1997. The longitudinal character of this article gives a strong
      practice-based evidence for weight management by GPs.

PMID- 22399560
TI  - The BeweegKuur programme: a qualitative study of promoting and impeding factors
      for successful implementation of a primary health care lifestyle intervention for
      overweight and obese people.
AB  - BACKGROUND: The aim of the study was to identify promoting and impeding factors
      for successful implementation of a Dutch primary health care-based lifestyle
      programme called 'BeweegKuur'. BeweegKuur aims to increase the physical activity
      and change the diet of people at increased health risk due to overweight or
      obesity. OBJECTIVE: To determine perceived promoting and impeding factors in the
      implementation of the BeweegKuur programme for overweight and obese people.
      METHODS: This study consisted of 3 focus group meetings with intervention
      participants, 15 interviews with health care professionals (HCPs) and 1 focus
      group session with dieticians. The interviews and focus groups were recorded and
      transcribed verbatim. The data were analysed with the Nvivo qualitative research
      software package. RESULTS: For some intervention participants, the invitation to
      participate in BeweegKuur came unexpectedly, as they had not been diagnosed with
      an illness. HCPs were aware of this and took time to explain to participants that
      the programme was appropriate and safe for them. Participants as well as
      professionals were generally positive about the feasibility of the programme for
      overweight and obese people. CONCLUSIONS: HCPs as well as intervention
      participants were motivated to participate in the programme, and generally
      indicated that the intervention was in accordance with their needs. The
      multidisciplinary approach and the combination of physical activity and dietary
      behaviour change can make the BeweegKuur programme a success if potential
      impeding factors like those identified in the present study are overcome.

PMID- 22399561
TI  - Changes in self-reported energy balance behaviours and body mass index during a
      mass media campaign.
AB  - BACKGROUND: Prevention of (serious) overweight can be achieved by means of small
      behaviour changes in physical activity and/or diet. OBJECTIVE: To evaluate a mass
      media campaign promoting energy balance behaviours in a Dutch population. Effects
      were examined for body mass index (BMI) and five energy balance behaviours.
      METHODS: A representative cohort study of 1200 Dutch adults was employed. Data
      were collected at four moments. Two campaign waves were launched, following T1
      (targeting the general adult population) and T2 [targeting low socio-economic
      status (SES) men], respectively. Regression analyses were performed to estimate
      the short-term and long-term effects of campaign exposure. RESULTS: In total,
      data of 1030 participants (86%) were available. Time trends showed unfavourable
      changes in most but not all energy balances behaviour for the total sample. No
      differences were found for BMI. No differences in the outcome measures were found
      as a result of exposure to the first campaign (19%). A short-term effect of
      exposure to the second campaign (29% exposure) was found (T2-T3), but only for
      low SES respondents, with increases in the attention being paid towards food
      choice (P = 0.02). At long term, BMI was less likely to increase among exposed
      people with a non-Dutch ethnicity (P = 0.01, T2-T4). CONCLUSIONS: Exposure to the
      campaign was low. The first campaign wave had no effects on BMI and energy
      balance behaviours. Small but favourable changes in attention towards food choice
      and BMI for at-risk populations were observed among those exposed to the second
      campaign wave.

PMID- 22399562
TI  - Nutrition awareness before and throughout different trimesters in pregnancy: a
      quantitative study among Dutch women.
AB  - OBJECTIVE: To examine the nutrition awareness of women before and during
      pregnancy in order to provide a greater understanding of the life course
      perspective (LCP) in relation to nutrition behaviours and pregnancy. METHOD: Data
      were collected in a cross-sectional study with the aid of a face-to-face
      interview, based on our conceptualization of nutrition awareness and the 'rules
      of thumb' designed by the Dutch Nutrition Centre. The sample consisted of five
      groups each of ~100 Dutch nulliparous women: women not trying to conceive a
      child, women trying to conceive a child and women in their first, second or third
      trimesters of pregnancy. RESULTS: The measurement tool based on our
      conceptualization of nutrition awareness resulted in a Cronbach's alpha of 0.84.
      Pregnant women are significantly more aware of their nutrition than women who are
      not trying to conceive. The scores on nutrition awareness do not differ
      significantly between the three trimester groups of pregnant women. Women who are
      trying to conceive do not have a significantly higher nutrition awareness than
      women who are not trying to conceive. CONCLUSIONS: Our conceptualization of
      nutrition awareness has shown to be fruitful in obtaining a better understanding
      of behavioural changes in health. The study provided indications in favour of the
      LCP; pregnancy could indeed be an event in a woman's life that causes increased
      nutrition awareness. This should be kept in mind when healthy nutrition promotion
      activities are being developed.

PMID- 22399563
TI  - Undernutrition in older adults.
AB  - Undernutrition in older persons usually presents as weight loss and is
      predominantly due to protein energy wasting. The presentation of undernutrition
      is often subtle in older persons and there is a need to utilize screening tools
      and increasing physician awareness. There are multiple treatable causes of
      undernutrition in older persons. The major causes are anorexia, cachexia,
      sarcopenia, dehydration, malabsorption and hypermetabolism. This article also
      provides an overview of the use of nutritional supplements and an approach to
      managing protein energy wasting.

PMID- 22399564
TI  - Generalizability of systematic reviews of the effectiveness of health care
      interventions to primary health care: concepts, methods and future research.
AB  - BACKGROUND: There is a push to make clinical decision making more evidence based
      and patient oriented. However, current systematic reviews are limited by the lack
      of consideration of generalizability. OBJECTIVE: To develop a guide for
      investigators (systematic reviewers) on how to adapt the methodology of a
      systematic review to facilitate the exploration of the results to primary care.
      METHODS: We reviewed the method guidelines of five organizations and working
      groups. Then, we conducted a search of literature in PubMed for articles on
      external validity of systematic. Based on the literature, we developed general
      steps to incorporate generalizability in systematic reviews and then integrated
      main primary care themes as outlined in WONCA definition of primary care and the
      definition of person-centred medicine across those steps. RESULTS: We identified
      a wide variety of approaches to address the issue of generalizability in
      systematic reviews. We extracted four major primary care themes from the two
      definitions of primary care and person-centred medicine that we mapped across the
      methods of generalizability. We suggested a two-step approach: Step 1 planning
      the scope of a review using four-layer schematic model and Step 2 to follow four
      steps to incorporate the concept of generalizability to primary care in the
      review. CONCLUSIONS: Systematic reviewers can take several steps to improve the
      generalizability of their review to primary care. However, more research is
      needed to determine which approach provides better results than others.

PMID- 22399566
TI  - Resident confidence addressing social history: is it influenced by availability
      of social and legal resources?
AB  - BACKGROUND: Pediatric residency clinics caring for underserved populations are
      often staffed with varying levels of social and legal resources, though their
      effects on residents' knowledge and practice have not been studied. Aim To
      examine the effects of clinic-based social and legal resources on resident
      knowledge and screening patterns for social determinants of health. METHODS: A
      cross-sectional study of residents from 3 continuity clinics with different
      social and legal resources was performed. Resident surveys assessing their
      knowledge and screening practices, and direct observation of social history
      taking was compared. RESULTS: Forty resident surveys revealed that those from
      clinics with more social and legal resources had greater confidence in their
      knowledge, screened more frequently, and spent more time taking social histories
      as assessed on direct observation. CONCLUSIONS: Residents who practiced in
      continuity clinics with increased social and legal resources were more confident
      in their knowledge and screened for social determinants of health more
      frequently.

PMID- 22399567
TI  - Parental perception of the effectiveness of treatments for infant nasal
      congestion.

PMID- 22399565
TI  - Loss of transforming growth factor beta type II receptor increases aggressive
      tumor behavior and reduces survival in lung adenocarcinoma and squamous cell
      carcinoma.
AB  - PURPOSE: Lung adenocarcinoma and lung squamous cell carcinoma (SCC) are the most
      common non-small cell lung cancer (NSCLC) subtypes. This study was designed to
      determine whether reduced expression of TGFbeta type II receptor (TGFbetaRII)
      promotes lung adenocarcinoma and SCC carcinogenesis. EXPERIMENTAL DESIGN: We
      examined TGFbetaRII expression at the protein and mRNA levels in human NSCLC
      samples and assessed the relationship between TGFbetaRII expression and
      clinicopathologic parameters. To determine whether sporadic TGFbetaRII deletion
      in airway epithelial cells induces NSCLC formation, we targeted TGFbetaRII
      deletion alone and in combination with oncogenic Kras(G12D) to murine airways
      using a keratin 5 (K5) promoter and inducible Cre recombinase. RESULTS: Reduced
      TGFbetaRII expression in human NSCLC is associated with male gender, smoking, SCC
      histology, reduced differentiation, increased tumor stage, increased nodal
      metastasis, and reduced survival. Homozygous or heterozygous TGFbetaRII deletion
      in mouse airway epithelia increases the size and number of Kras(G12D)-initiated
      adenocarcinoma and SCC. TGFbetaRII deletion increases proliferation, local
      inflammation, and TGFbeta ligand elaboration; TGFbetaRII knockdown in airway
      epithelial cells increases migration and invasion. CONCLUSIONS: Reduced
      TGFbetaRII expression in human NSCLC is associated with more aggressive tumor
      behavior and inflammation that is, at least partially, mediated by increased
      TGFbeta1 expression. TGFbetaRII deletion in mouse airway epithelial cells
      promotes adenocarcinoma and SCC formation, indicating that TGFbetaRII loss plays
      a causal role in lung carcinogenesis. That TGFbetaRII shows haploid insufficiency
      suggests that a 50% TGFbetaRII protein reduction would negatively impact lung
      cancer prognosis.

PMID- 22399568
TI  - Caregivers' baseline understanding and expectations of antibiotic use for their
      children.
AB  - Although there is evidence that oral antibiotic prescriptions for children have
      decreased since the 1990s, antibiotic resistance continues to be a problem. This
      study evaluated the caregivers' understanding of antibiotic use for their
      children and identified demographic characteristics that may contribute to
      inappropriate antibiotic-seeking behavior. Caregivers were asked how often the
      child should receive antibiotics for common medical conditions and about factors
      to improve patient compliance. This study found that caregivers overexpected
      antibiotic use with upper respiratory infection, ear infection, and pneumonia.
      Caretakers with lower incomes and on Medicaid comprised the higher percentage of
      overusers. The most important factors to improve patient compliance were
      explanation of the name and indication for antibiotic use. This study showed that
      demographic variables play a role in caregivers' expectations of antibiotic use.
      Effective communication of physicians with caregivers on antibiotic use can be an
      important strategy to improve patient compliance.

PMID- 22399569
TI  - Fever, jaundice, and liver failure in an 18-year-old male.

PMID- 22399570
TI  - Language development survey provides a useful screening tool for language delay
      in preterm infants.
AB  - Developmental language disorder has been reported in 3% to 10% of term infants
      and 30% of preterm infants (<34 weeks gestation). Screening for language delay in
      preterm infants can be costly and time-consuming. The objective of this study was
      to assess the expressive language development of preterm infants using the
      Language Development Survey (LDS). A total of 178 preterm infants born at 23 to
      34 weeks between 2006 and 2008 were enrolled. The LDS was completed by parents
      between 22 and 26 months at or shortly before 2-year neurodevelopmental
      assessment using the Bayley III Scale. A total of 26% of former preterm patients
      had language delay, using LDS. Significant correlations were observed between LDS
      results and Bayley III scores. Male gender and public health insurance were the
      most important risk factors for language delay in this cohort. Expressive
      language delay was present in 26% of preterm infants. LDS is a suitable and
      inexpensive screening tool for assessing language delay in preterm infants.

PMID- 22399571
TI  - Attention-deficit/hyperactivity disorder among children and adolescents in the
      United States: trend in diagnosis and use of pharmacotherapy by gender.

PMID- 22399572
TI  - The origin, global distribution, and functional impact of the human 8p23
      inversion polymorphism.
AB  - Genomic inversions are an increasingly recognized source of genetic variation.
      However, a lack of reliable high-throughput genotyping assays for these
      structures has precluded a full understanding of an inversion's phylogenetic,
      phenotypic, and population genetic properties. We characterize these properties
      for one of the largest polymorphic inversions in man (the ~4.5-Mb 8p23.1
      inversion), a structure that encompasses numerous signals of natural selection
      and disease association. We developed and validated a flexible bioinformatics
      tool that utilizes SNP data to enable accurate, high-throughput genotyping of the
      8p23.1 inversion. This tool was applied retrospectively to diverse genome-wide
      data sets, revealing significant population stratification that largely follows a
      clinal "serial founder effect" distribution model. Phylogenetic analyses
      establish the inversion's ancestral origin within the Homo lineage, indicating
      that 8p23.1 inversion has occurred independently in the Pan lineage. The human
      inversion breakpoint was localized to an inverted pair of human endogenous
      retrovirus elements within the large, flanking low-copy repeats; experimental
      validation of this breakpoint confirmed these elements as the likely intermediary
      substrates that sponsored inversion formation. In five data sets, mRNA levels of
      disease-associated genes were robustly associated with inversion genotype.
      Moreover, a haplotype associated with systemic lupus erythematosus was restricted
      to the derived inversion state. We conclude that the 8p23.1 inversion is an
      evolutionarily dynamic structure that can now be accommodated into the
      understanding of human genetic and phenotypic diversity.

PMID- 22399573
TI  - Identification of novel causative genes determining the complex trait of high
      ethanol tolerance in yeast using pooled-segregant whole-genome sequence analysis.
AB  - High ethanol tolerance is an exquisite characteristic of the yeast Saccharomyces
      cerevisiae, which enables this microorganism to dominate in natural and
      industrial fermentations. Up to now, ethanol tolerance has only been analyzed in
      laboratory yeast strains with moderate ethanol tolerance. The genetic basis of
      the much higher ethanol tolerance in natural and industrial yeast strains is
      unknown. We have applied pooled-segregant whole-genome sequence analysis to map
      all quantitative trait loci (QTL) determining high ethanol tolerance. We crossed
      a highly ethanol-tolerant segregant of a Brazilian bioethanol production strain
      with a laboratory strain with moderate ethanol tolerance. Out of 5974 segregants,
      we pooled 136 segregants tolerant to at least 16% ethanol and 31 segregants
      tolerant to at least 17%. Scoring of SNPs using whole-genome sequence analysis of
      DNA from the two pools and parents revealed three major loci and additional minor
      loci. The latter were more pronounced or only present in the 17% pool compared to
      the 16% pool. In the locus with the strongest linkage, we identified three
      closely located genes affecting ethanol tolerance: MKT1, SWS2, and APJ1, with
      SWS2 being a negative allele located in between two positive alleles. SWS2 and
      APJ1 probably contained significant polymorphisms only outside the ORF, and lower
      expression of APJ1 may be linked to higher ethanol tolerance. This work has
      identified the first causative genes involved in high ethanol tolerance of yeast.
      It also reveals the strong potential of pooled-segregant sequence analysis using
      relatively small numbers of selected segregants for identifying QTL on a genome
      wide scale.

PMID- 22399574
TI  - Factors affecting chronic obstructive pulmonary disease early rehospitalization.
AB  - The Centers for Medicare and Medicaid Services has identified early
      rehospitalization of patients with chronic obstructive pulmonary disease (COPD)
      exacerbations as a performance measure for hospital care. We retrospectively
      reviewed patients with COPD who were admitted to University Medical Center,
      Lubbock, Texas, USA, between October 2010 and March 2011. There were 81 COPD
      patients with 103 hospitalizations. The mean age was 73.9 years. Pulmonary
      function tests using the Global initiative for chronic Obstructive Lung Disease
      criteria had been done in 36 patients (44.4%) and revealed 1 mild (2.8%), 7
      moderate (19.4%), 20 severe (55.6%), and 8 very severe (22.2%) cases. Only 38.4%
      of the patients had prior influenza vaccine. Most patients were treated with
      antibiotics (81.8%) and corticosteroids (87.9%). The mean length of stay was 4.9
      days, and 4 patients died. Most of the patients were discharged home (63.6%) with
      a median follow-up interval of 14 days. Thirty-two percent did not have long
      acting bronchodilators and/or inhaled corticosteroids prescribed on discharge.
      There were 14 early rehospitalizations within 30 days. Logistic regression
      analysis indicated that a history of coronary artery disease (odds ratio (OR)
      6.4, 95% confidence interval (CI) 1.1-37.4) and unilateral pulmonary infiltrates
      (OR 12.8, 95% CI 1.9-86.4) significantly increased the early rehospitalization
      rates. Acute exacerbations of COPD in patients with a history of ischemic heart
      disease or unilateral pulmonary infiltrates are at increased risk for early
      readmission. These risk factors should be identified during hospitalization;
      early follow-up or other interventions may reduce readmissions. Influenza
      vaccine, maintenance bronchodilators and/or inhaled corticosteroids, and
      pulmonary function tests were underused, and these standards of care should be
      provided to improve care.

PMID- 22399575
TI  - Quadriceps function in anterior cruciate ligament-deficient knees exercising with
      transcutaneous electrical nerve stimulation and cryotherapy: a randomized
      controlled study.
AB  - OBJECTIVE: To compare strength and quadriceps muscle activation in anterior
      cruciate ligament-deficient patients who underwent a two-week rehabilitation
      exercise program using TENS or cryotherapy. DESIGN: Randomized, controlled study.
      SETTING: Clinical research laboratory. SUBJECTS: Thirty patients: 20 males, 10
      females, 31.6 (13.0) years, 172.8 (10.0) cm, 75.8 (13.0) kg with diagnosed tear
      of the anterior cruciate ligament. INTERVENTIONS: All patients attended four
      sessions of supervised quadriceps strengthening exercises over two weeks, prior
      to reconstruction surgery. Patients were randomly allocated (n = 10/group) to
      receive exercises alone, exercise while wearing a sensory transcutaneous
      electrical nerve stimulation (TENS) device on the knee joint for the duration of
      each daily session, or 20 minutes of knee joint cryotherapy immediately prior to
      each daily exercise session. MAIN MEASURES: Normalized knee extension force and
      quadriceps central activation ratio were measured before and after the first
      supervised treatment session and within 24 hours of the last session. RESULTS:
      When accounting for differences in baseline measures, there were no statistically
      significant group differences immediately following the first exercise session
      for knee extension force (P = 0.10) or central activation ratio (P = 0.30) nor
      were there statistically significant group differences after the two-week
      intervention for knee extension force (P = 0.92) or central activation ratio (P =
      0.94). Effect sizes for the change in knee extension force and central activation
      ratio after two weeks of therapy were all large. CONCLUSIONS: Quadriceps strength
      and central activation in anterior cruciate ligament deficient patients improved
      after two weeks of rehabilitaiton exercises, however, there were no significant
      differences between treatment groups.

PMID- 22399576
TI  - Integrating varieties of life course concepts.
AB  - A body of work referred to as the "life course" framework (also known as "life
      course theory," the "life course paradigm," and the "life course perspective")
      has been increasingly used to motivate and justify the examination of the
      relationships among variables in social and behavioral science, particularly in
      the study of population health and aging. Yet, there is very little agreement on
      what some of these concepts mean, and there is hardly any agreement on what the
      "life course" is. This article focuses on the different ways in which the concept
      of "life course" is used in the contemporary study of aging and human
      development, particularly with regard to health and well-being. Clarification is
      given for how "life course" is distinguished from "life span" and "life cycle,"
      among other "life" words. This work reviews the conceptual literature on the life
      course, beginning with its formative years in the 1960s and 1970s, through to the
      present time. Detailed research of several literatures across disciplines
      revealed five different uses of the term "life course": (a) life course as time
      or age, (b) life course as life stages, (c) life course as events, transitions,
      and trajectories, (d) life course as life-span human development, and (e) life
      course as early life influences (and their cumulation) on later adult outcomes.
      To the extent the concept of life course has a multiplicity of meanings that are
      at variance with one another, this is problematic, as communication is thereby
      hindered. On the other hand, to the extent the concept of life course involves a
      rich tapestry of different emphases, this is a good thing, and the diversity of
      meanings should be retained. This paper proposes a conceptual integration based
      in part on Riley's age stratification model that resolves the various meanings of
      life course into one general framework. Coupled with a demographic
      conceptualization of the life course, this framework embeds the concept of "life
      course" within a broader perspective of life-span development. This framework is
      proposed as an integrated perspective for studying the causes and consequences of
      "life course events and transitions" and understanding the manner by which "life
      events" and the role transitions they signify influence the life-span development
      of outcomes of interest across stages of the life cycle.

PMID- 22399577
TI  - Plus ca change, plus c'est la meme chose: latest words on "life words".

PMID- 22399578
TI  - Hispanic Baby Boomers: health inequities likely to persist in old age.
AB  - PURPOSE: As the Baby-Boom generation enters the ranks of the elderly adults over
      the next 4 decades, the United States will witness an unprecedented growth in
      racial/ethnic diversity among the older adult population. Hispanics will comprise
      20% of the next generation of older adults, representing the largest minority
      population aged 65 years and older, with those of Mexican-origin comprising the
      majority of Hispanics. Little is known about the health status of this
      population. DATA/METHODS: Data are for Baby Boomers born between 1946 and 1964
      (ages 43-61) in the 2007 California Health Interview Survey. Logistic regression
      estimates the odds of diabetes, hypertension, obesity, fair/poor self-rated
      health (SRH), and functional difficulties among U.S.-born non-Hispanic Whites
      (NHW), U.S.-born Mexicans, naturalized Mexican immigrants, and noncitizen Mexican
      immigrants. RESULTS: The Mexican-origin populations are disadvantaged relative to
      NHW for all socioeconomic status (SES) and several health outcomes. The Mexican
      origin disadvantage in health attenuates when controlling for SES and
      demographics, but the disadvantage remains for diabetes, obesity, and fair/poor
      SRH. IMPLICATIONS: Baby Boomers of Mexican origin do not share the advantages of
      health, income, and educational attainment enjoyed by U.S.-born NHW. As this
      cohort moves into old age, the cumulative disadvantage of existing disparities
      are likely to result in continued or worse health disparities. Reductions in
      federal entitlement programs for the elderly adults that delay eligibility, scale
      back programs and services, or increase costs to consumers may exacerbate those
      inequities.

PMID- 22399581
TI  - Suppressing publication threatens scientific progress.

PMID- 22399580
TI  - Intentions to quit work among care staff working in the aged care sector.
AB  - PURPOSE OF THE STUDY: The aged care industry experiences high rates of staff
      turnover. Staff turnover has significant implications for the quality of care
      provided to care recipients and the financial costs to care agencies. In this
      study, we applied a model of intention to quit to identify the contextual and
      personal factors that shape aged care staff's intention to quit. DESIGN AND
      METHODS: A sample of 208 aged care staff, including nurses, personal care
      assistants, allied health professionals, and managers completed a self-report
      questionnaire. The questionnaire assessed intention to quit, organizational
      commitment, job satisfaction, self-esteem, stressors, stress, and supervisor
      support. RESULTS: The findings largely supported the model. Specifically, job
      commitment, job satisfaction, and work stressors directly influenced intentions
      to quit, although work stressors and supervisor support demonstrated numerous
      indirect associations on quitting intentions. IMPLICATIONS: The findings suggest
      that aged care service providers can modify aged care workers' intentions to quit
      by reducing job stressors and increasing supervisor support.

PMID- 22399582
TI  - Natural variation in Hd17, a homolog of Arabidopsis ELF3 that is involved in rice
      photoperiodic flowering.
AB  - Flowering time of rice depends strongly on photoperiodic responses. We previously
      identified a quantitative trait locus, Heading date 17 (Hd17), that is associated
      with a difference in flowering time between Japanese rice (Oryza sativa L.)
      cultivars. Here, we show that the difference may result from a single nucleotide
      polymorphism within a putative gene that encodes a homolog of the Arabidopsis
      EARLY FLOWERING 3 protein, which plays important roles in maintaining circadian
      rhythms. Our results demonstrate that natural variation in Hd17 may change the
      transcription level of a flowering repressor, Grain number, plant height and
      heading date 7 (Ghd7), suggesting that Hd17 is part of rice's photoperiodic
      flowering pathway.

PMID- 22399583
TI  - Cardiac hormones are c-Jun-N-terminal kinase 2-inhibiting peptides.
AB  - BACKGROUND: Four cardiac peptide hormones, namely vessel dilator, long-acting
      natriuretic peptide (LANP), kaliuretic peptide, and atrial natriuretic peptide
      (ANP) have anticancer effects. MATERIALS AND METHODS: The effects of these four
      cardiac hormones on human c-Jun-N-terminal kinase 2 (JNK2) were examined in human
      small cell lung cancer and human prostate cancer cells. RESULTS: Vessel dilator,
      LANP, kaliuretic peptide and ANP maximally reduced expression of JNK2 by 89%,
      56%, 45%, and 28%, respectively (each at p<0.0001) in human small cell lung
      cancer cells. In human prostate adenocarcinoma cells, JNK2 was maximally
      decreased 76%, 56%, 45%, (each at p<0.0001), and 28% (p<0.01) secondary to vessel
      dilator, LANP, kaliuretic peptide and ANP, respectively. CONCLUSION: These
      results indicate that four cardiac hormones are significant inhibitors (by up to
      89%) of JNK2 in human small cell lung cancer cells and up to 76% in human
      prostate adenocarcinoma cells as part of their anticancer mechanism(s) of action.

PMID- 22399584
TI  - Effect of dietary vitamin D and calcium on the growth of androgen-insensitive
      human prostate tumor in a murine model.
AB  - Vitamin D deficiency has been associated with increased risk of prostate cancer
      (PC) in epidemiologic and prospective studies. An association has also been made
      between high dietary calcium and increased PC risk. In this study, we evaluated
      the effect of dietary vitamin D and calcium on the growth of human androgen
      insensitive prostate tumor in an athymic mouse model. We observed highest tumor
      growth in the normal calcium - vitamin D-deficient group, while tumor growth
      between the normal calcium - vitamin D-sufficient, high calcium - vitamin D
      sufficient and high calcium - vitamin D-deficient diet-groups did not
      significantly differ but was significantly lower than that in the normal calcium 
      vitamin D-deficient group. Our results suggest an important role of dietary
      vitamin D as a preventive agent in androgen-insensitive PC.

PMID- 22399585
TI  - Stem-like cells in bladder cancer cell lines with differential sensitivity to
      cisplatin.
AB  - BACKGROUND: Recurrence is a common problem in bladder cancer; this has been
      attributed to cancer stem cells. In this study, we characterized potential cancer
      stem cell populations isolated from three cell lines that demonstrate different
      responses to cisplatin. MATERIALS AND METHODS: The ALDEFLUOR(r) assay was used to
      isolate cells from TCCSUP, T24, and 5637 cell lines, and these cells were
      evaluated for their ability to form colonies, differentiate, migrate and invade.
      RESULTS: The cell lines demonstrate a spectrum of aldehyde dehydrogenase high
      (ALDH(High)) populations that correlate with resistance to cisplatin. In the two
      resistant cell lines, T24 and 5637, the ALDH(High) cells demonstrate increased
      colony formation, migration, invasion, and ability to differentiate. The
      resistant T24 and 5637 cell lines may serve as models to investigate alternative
      therapies for bladder cancer.

PMID- 22399586
TI  - 20-hydroxyvitamin D3 inhibits proliferation of cancer cells with high efficacy
      while being non-toxic.
AB  - AIM: To define the potential utility of 20-hydroxyvitamin D(3) (20(OH)D(3)) as a
      tumorostatic agent, we assessed its in vitro antiproliferative activity and its
      in vivo toxicity. MATERIALS AND METHODS: The antitumor activity of 20(OH)D(3) was
      tested against breast and liver cancer cell lines using colony formation assays.
      To assess in vivo toxicity, mice were injected with 5-30 MUg/kg 20(OH)D(3)
      intraperitoneally each day for 3 weeks. Blood and organ samples were collected
      for clinical pathology analyses. RESULTS: 20(OH)D(3) displays similar
      tumorostatic activity towards MDA-MB-453 and MCF7 breast carcinomas, and HepG2
      hepatocarcinoma, in a dose-dependent manner. This compound is not hypercalcemic,
      does not cause detectable toxicities in liver, kidney, or blood chemistry in mice
      at a dose as high as 30 MUg/kg. In contrast, both 25(OH)D(3) and 1,25(OH)(2)D(3)
      caused severe hypercalcemia at a dose of 2 MUg/kg. CONCLUSION: 20(OH)D(3)
      possesses high efficacy for inhibiting cancer cell proliferation in vitro and is
      non-toxic in vivo, supporting its further development as a potential anticancer
      therapeutic agent.

PMID- 22399587
TI  - Metallothionein expression in canine cutaneous apocrine gland tumors.
AB  - BACKGROUND: The aim of the present study was to evaluate, by immunohistochemical
      staining, metallothionein expression in normal, benign and malignant canine
      apocrine gland tissues and to correlate the protein expression with the
      histological grade of malignancy. MATERIALS AND METHODS: MT immunostaining was
      evaluated in 25 formalin-fixed and paraffin-embedded canine apocrine glands (2
      normal and 23 neoplastic). Moreover, we evaluated quantitative expression of MT
      in normal and neoplastic cells by western blotting. RESULTS: a marked increase in
      MT expression was observed in neoplastic, compared to normal samples as well as
      in malignant compared to benign tumors. Western blotting analysis revealed one
      major protein band of approximately 14 kDa in normal, as well as in the
      neoplastic, tissues. CONCLUSION: We conclude that MT expression appears to be a
      potential biomarker for the diagnosis of canine apocrine gland tumors and may
      also assist in the better understanding of the evolution of this neoplasia.

PMID- 22399588
TI  - Ceramide synthase 6 knockdown suppresses apoptosis after photodynamic therapy in
      human head and neck squamous carcinoma cells.
AB  - BACKGROUND: The effectiveness of photodynamic therapy (PDT) for cancer treatment
      correlates with apoptosis. We observed that suppression of de novo-generated
      sphingolipids, e.g. ceramide, renders cells resistant to apoptosis post-PDT.
      Ceramide synthase 6 (CerS6) has been implicated in apoptosis after various
      stimuli. AIM: To investigate the involvement of down-regulation of CerS6 in
      apoptosis and its impact on the sphingolipid profile post-PDT with the silicone
      phthalocyanine Pc 4 in a human head and neck squamous carcinoma cell line.
      MATERIALS AND METHODS: Besides siRNA transfections and PDT treatment,
      immunoblotting for protein expression, mass spectrometry for sphingolipid
      analysis, spectroflurometry and flow cytometry for apoptotic marker detection,
      and trypan blue assay for cytotoxicity assessment, were used. RESULTS: CerS6
      knockdown led to reduction in PDT-induced DEVDase activation, mitochondrial
      depolarization, apoptosis and cell death. CerS6 knockdown was associated with
      selective decreases in ceramides and dihydroceramides, markedly of C18
      dihydroceramide, post-PDT. CONCLUSION: CerS6 might be a novel therapeutic target
      for regulating apoptotic resistance to PDT.

PMID- 22399589
TI  - Receptor affinity and preclinical biodistribution of radiolabeled somatostatin
      analogs.
AB  - In this study, we investigated the relationship between affinity to somatostatin
      receptor subtype2 (SSTR(2)) and uptake of radioactivity from a group of
      radiolabeled somatostatin analogues in somatostatin receptor-rich tissues of
      rats. Organs with a high density of somatostin receptors (namely the adrenals and
      pancreas bearing mainly SSTR(2); this receptor subtype is also the most abundant
      in somatostatin receptor-positive tumors) were chosen as markers of specific
      binding of the peptides in vivo. Accumulations of radioactivity in these organs
      24 h and 48 h after intravenous administration of six (111)In-labeled octreotide
      and octreotate derivatives with predominant affinity to SSTR(2) were correlated
      with affinity to SSTR(2) determined in vitro (IC(50) values). For correlation
      between adrenal uptake of radioactivity and IC(50), the best fit for exponential
      dependence was found; for that of pancreas, however, linear dependence was the
      most suitable. In cases where the values for the peptide with affinity to SSTR
      subtypes 2, 3 and 5, namely (111)In-DOTA-Nal(3)-octreotide were included in the
      group of studied agents, substantially less correlations were obtained. Our
      results showed that uptake of radioactivity in tissues with a high density of
      somatostatin receptors correlates with somatostatin receptor affinity of receptor
      specific peptides; however, other factors (the affinity to particular receptor
      subtypes, the overall pharmacokinetic profile in the body etc.) may contribute to
      this observed relationship.

PMID- 22399590
TI  - In vitro blockade of adhesion of breast cancer cells to endothelial cells using
      anti-inflammatory drugs.
AB  - BACKGROUND: Increasing evidence suggests that a pro-inflammatory microenvironment
      affects distant metastasis of breast cancer cells, in particular by favoring
      tumor cell adhesion to endothelium. The aim of this study was to investigate the
      potential of different anti-inflammatory drugs to inhibit this effect in vitro.
      MATERIALS AND METHODS: Breast cancer cells from the metastatic cell line KM22
      were incubated with activated Human umbilical vein endothelial cells (HUVECs).
      Tumor cell adhesion was quantified by fluorescence microscopy. The anti
      inflammatory drugs ibuprofen, aspirin (acetylsalicylic acid), diclofenac, and
      dexamethasone were used as inhibiting agents. RESULTS: Aspirin and dexamethasone
      significantly reduced breast cancer cell adhesion to HUVECs (20.3%, p<0.000; and
      25%, p<0.05, respectively). Ibuprofen and diclofenac did not significantly reduce
      tumor cell adhesion. CONCLUSION: Aspirin and dexamethasone seem to be able to
      partly inhibit adhesion of breast cancer cells to endothelium. Future studies
      should attempt to optimize this effect in vitro, in preparation for potential in
      vivo trials.

PMID- 22399591
TI  - Tissue microarray technique in evaluation of proliferative activity in invasive
      ductal breast cancer.
AB  - AIM: Investigation of the relationship between expression of Ki-67 antigen and
      minichromosome maintenance 2 (MCM-2) protein by using an immunohistochemical
      study on whole sections (WS) and sections of invasive ductal breast cancer (IDC)
      obtained in the tissue microarray (TMA) technique. MATERIALS AND METHODS:
      Material consisted of 51 archival paraffin blocks of IDC. Tissue microarrays were
      composed of 0.6 mm core punches. Reactions were performed using specific
      antibodies (anti-Ki-67 and anti-MCM-2). Intensity of the marker expression was
      evaluated using computer-assisted image analysis. For statistical purposes, three
      different tests were used. RESULTS: Spearman rank correlation revealed a strong
      positive correlation between expression of tested markers: Ki-67 (TMA) vs. Ki-67
      (WS) (r=0.91, p<0.05) and MCM-2 (TMA) vs. MCM-2 (WS) (r=0.87, p<0.05). Mann
      Whitney U-test showed no significant differences between the two markers in both
      analysed techniques. Moreover, the Bland-Altman plot demonstrated a low level of
      bias between the analysed methods. CONCLUSION: This study shows that TMA could
      have a great potential in evaluation of proliferative activity in IDC and that
      MCM-2 protein might be a specific and sensitive marker of cell proliferation.

PMID- 22399592
TI  - Antitumor activity of an interleukin-2 monoclonal antibody in a murine
      osteosarcoma transplantation model.
AB  - BACKGROUND: Injection of monoclonal antibody to interleukin-2 (S4B6) into mice
      depletes regulatory T-cells (Tregs) and exhibits antitumor activities mediated
      through an autoimmune reaction. In this study, we demonstrate that administration
      of S4B6 suppresses the murine osteosarcoma cell line, LM8. MATERIALS AND METHODS:
      LM8 osteosarcoma cells were transplanted subcutaneously into C3H mice (n=58). C3H
      mice were injected intraperitoneally with S4B6 starting at 7 days before LM8
      transplantation (pre-S4B6 group), 2 days after transplantation, or 5 days after
      transplantation. Control group mice were injected with normal rat IgG. Mice were
      sacrificed and examined 4 weeks later. RESULTS: The number of pulmonary
      metastatic colonies and the tumor size were significantly reduced in the pre-S4B6
      group compared to the control group. In addition, pulmonary metastases were
      inhibited in mice injected with S4B6 2 days, but not 5 days, after tumor
      transplantation. CONCLUSION: S4B6 administration inhibited metastasis even when
      injected 2 days after LM8 transplantation. Our data suggest that treatment with
      S4B6 might be suitable in a postoperative clinical setting.

PMID- 22399593
TI  - Cetuximab sensitivity associated with oxaliplatin resistance in colorectal
      cancer.
AB  - BACKGROUND: Clinical studies have suggested that the epidermal growth factor
      receptor (EGFR)-inhibiting antibody cetuximab may have better effect in the third
      line treatment of metastatic colorectal cancer, after failure of standard
      chemotherapy including oxaliplatin, compared to using it up-front in the first
      line. The reason behind this suggestion is unclear. MATERIALS AND METHODS: The
      effect of cetuximab on cell growth was investigated in five isogenic colon cancer
      cell lines with increasing level of acquired oxaliplatin resistance. The
      expression of EGFR and the activity of down-stream signalling molecules were
      measured by western blot analyses. RESULTS: A marked increase in sensitivity to
      cetuximab, accompanied by an up-regulation of EGFR, was observed in the
      oxaliplatin-resistant cell lines. CONCLUSION: The connection between oxaliplatin
      resistance and cetuximab sensitivity has not been previously reported in the
      literature. Such a connection could be of clinical importance and constitutes a
      substantial an argument for saving cetuximab until later treatment lines, when
      the tumours have become chemotherapy resistant.

PMID- 22399594
TI  - Methylation of TFPI2 no longer detected in the serum DNA of colorectal cancer
      patients after curative surgery.
AB  - In our previous study, we used quantitative methylation-specific polymerase chain
      reaction (qMSP) to examine the methylation status of tissue factor pathway
      inhibitor 2 (TFPI2) in the preoperative serum DNA of 215 colorectal cancer
      patients and found that TFPI2 was methylated in serum DNA from 39 of these
      patients. In this study, we examined postoperative serum DNA, obtained within one
      month after surgery from 38 out of the 39 patients and found that TFPI2 was
      methylated in the serum DNA of only 18 (47%) of these patients, suggesting that
      TFPI2 methylation in the serum of the remaining colorectal cancer patients was
      abolished by surgical tumor reduction. Next, we examined the correlation between
      the presence of TFPI2 methylation in postoperative serum DNA and residual cancer
      status after surgery. If R0 (no residual cancer) operations were successfully
      performed, TFPI2 methylation was not detected in postoperative serum. However, if
      R2 (obvious residual cancer) operations were performed, 17 (77%) out of 22
      postoperative sera, still exhibited TFPI2 methylation. Taken together, our
      results confirm that detection of methylated TFPI2 in serum DNA was derived from
      colorectal cancer and could serve as a marker of surgical outcome.

PMID- 22399595
TI  - Detection of vimentin methylation in the serum of patients with gastric cancer.
AB  - AIM: Detection of gastric cancer using serum assay of vimentin methylation.
      METHODS: A quantitative methylation-specific polymerase chain reaction assay was
      used to detect vimentin gene (VIM) methylation in the serum of 71 patients with
      gastric cancer. RESULTS: Mean VIM methylation in cancer patients (0.304 +/-
      0.558) was significantly higher than that in healthy donors (0.011 +/- 0.015,
      p=0.018). The sensitivity of VIM methylation (33.8%) was similar to the one of
      carbohydrate antigen 19-9 (CA19-9) (25.4%), higher than the one of
      carcinoembryonic antigen (CEA) (12.7%), and significantly higher than the
      sensitivity of both markers for patients with stage I and IV disease (p=0.010 and
      0.044, respectively). At all stages, the sensitivity of a combination of markers
      was higher than the sensitivity of any in isolation marker and was similar for
      stages I, II and III, reaching 76.9% for stage IV disease. CONCLUSION: VIM
      methylation may represent a useful marker for the detection of tumor DNA in the
      serum of patients with gastric cancer.

PMID- 22399596
TI  - Antiproliferative and antitumor effects of azacitidine against the human
      myelodysplastic syndrome cell line SKM-1.
AB  - BACKGROUND: The myelodysplastic syndromes (MDS) are a group of stem cell
      disorders characterized by dysplasia of one or more hematopoietic cell lineages
      and a risk of progression to acute myeloid leukemia. The cytidine analog
      azacitidine (Vidaza), a hypomethylating agent, improves survival in patients with
      MDS, but its mechanism of action is not well understood. MATERIALS AND METHODS:
      The effects of azacitidine on the MDS-derived cell line SKM-1 were investigated
      by DNA methylation assay, cell proliferation assay, and a subcutaneous xenograft
      mouse model. RESULTS: Azacitidine and decitabine induced hypomethylation of the
      tumor suppressor gene cyclin-dependent kinase 4 inhibitor B (CDKN2B) in SKM-1
      cells, whereas the deoxycytidine analog cytarabine did not. Azacitidine and
      decitabine also inhibited SKM-1 cell growth in vitro. In the mouse xenograft
      model, azacitidine significantly suppressed tumor growth. CONCLUSION: Inhibition
      of DNA methyltransferase by azacitidine contributes to its antiproliferative and
      antitumor effects against SKM-1 cells and may explain its clinical efficacy in
      MDS.

PMID- 22399598
TI  - Fucoxanthin induces GADD45A expression and G1 arrest with SAPK/JNK activation in
      LNCap human prostate cancer cells.
AB  - BACKGROUND/AIM: The antitumor effect of fucoxanthin, a marine carotenoid found in
      brown algae, was investigated on prostate cancer cells. MATERIALS AND METHODS:
      LNCap prostate cancer cells were treated with fucoxanthin and the effects were
      evaluated in relation to cell proliferation, cell cycle, expression of growth
      arrest, DNA damage-inducible protein (GADD45) genes, and phosphorylation status
      of mitogen-activated protein kinases. RESULTS: Fucoxanthin inhibited the growth
      of LNCap prostate cancer cells in a dose-dependent manner. Growth-inhibitory
      effects were accompanied by the induction of GADD45A expression and G(1) cell
      cycle arrest, but not apoptosis. Furthermore, fucoxanthin activated c-Jun N
      terminal kinase (SAPK/JNK), while the inhibition of SAPK/JNK attenuated the
      induction of G(1) arrest and GADD45A expression by fucoxanthin. CONCLUSION: These
      results show that fucoxanthin induces G(1) cell cycle arrest in prostate cancer
      cells, and suggest that ADD45A and SAPK/JNK might be involved in these effects.

PMID- 22399597
TI  - Transforming growth factor beta receptor I inhibitor sensitizes drug-resistant
      pancreatic cancer cells to gemcitabine.
AB  - BACKGROUND: Resistance to gemcitabine is a major obstacle in the treatment of
      advanced pancreatic cancer. Previous exploration of protein kinase inhibitors
      demonstrated that blocking transforming growth factor-beta (TGFbeta) signal
      enhances the efficacy of gemcitabine in pancreatic cancer cells. MATERIALS AND
      METHODS: We analyzed the cell viability after combinational treatment of TGFbeta
      receptor I (TbetaRI) inhibitors, SB431542 and SB525334 with gemcitabine in
      pancreatic cancer cells. In addition, apoptotic cell death and cell migration
      were measured. RESULTS: Combination with TbetaRI inhibitors significantly
      augmented the cytotoxicity of gemcitabine in both parental and gemcitabine
      resistant pancreatic cancer cells. SB525334 significantly increased apoptotic
      cell death in gemcitabine-resistant cells. Treatment of SB525334 also affected
      the AKT signalling pathway, which plays a crucial role in gemcitabine resistance.
      Migration assay also revealed that blocking TbetaRI reduces cell migration.
      CONCLUSION: Chemotherapeutic approaches using SB525334 might enhance the
      treatment benefit of the gemcitabine-containing regimens in the treatment of
      pancreatic cancer patients.

PMID- 22399599
TI  - Different radioactivity uptake between somatostatin analogues labelled with 111In
      and 90/88Y in rat kidney.
AB  - Somatostatin receptor targeting is a valuable method to treat somatostatin
      receptor-positive tumours. In peptide receptor radionuclide therapy, it is
      essential to determine the highest activity that can be safely administered to
      the patient. As (90)Y emits no gamma rays, absorbed doses for (90)Y are usually
      estimated using the same peptide labelled with (111)In. The aim of the study was
      to determine if replacement of (90/88)Y by (111)In affects the biodistribution
      profile of five selected somatostatin analogues in preclinical experiments.
      MATERIALS AND METHODS: Radiolabelled peptides were administered intravenously to
      male Wistar rats. RESULTS: The peptides under study labelled either with (111)In
      or with (88/90)Y showed similar distribution profiles in all tissues excepting
      the kidney. The kidney radioactivity uptake was significantly lower for (88/90)Y
      labeled peptide in comparison with the one of (111)In. CONCLUSION: We conclude
      that a radiation-absorbed dose after (90)Y-labelled somatostatin analogues
      appears to be lower than that predicted by the (111)In-labelled peptide.

PMID- 22399600
TI  - Enhanced renal clearance of vancomycin in rats with carcinogen-induced
      osteosarcoma.
AB  - Recently, it has been reported that total clearance (CLtot) of vancomycin is
      significantly higher in patients with malignancies compared to those without
      malignancies. In the present study, to clarify the mechanism of this enhancement
      in malignancy, we adopted rat animal models, using chemical carcinogen-induced
      osteosarcoma, selected lung metastatic lesions (C-SLM), transplanted into thigh
      muscles. The CLtot and renal clearance (CLr) of vancomycin in the tumor-bearing
      rats were increased compared to the ones of the control rats without tumor.
      However, there was no difference in the glomerular filtration rate. The plasma
      concentrations of interleukin (IL)-1beta and IL-6, were elevated in the tumor
      bearing rats. When renal proximal tubular epithelial cells (RPTEC) were exposed
      to IL-1beta, IL-6, and tumor necrosis factor (TNF)-alpha simultaneously, the
      excretory ratio increased significantly. These findings suggest that tubular
      excretion or re-absorption by cytokines might be associated with changes in the
      vancomycin CLtot enhancement in the tumor-bearing rats.

PMID- 22399601
TI  - Farnesyltransferase inhibitors: molecular evidence of therapeutic efficacy in
      acute lymphoblastic leukemia through cyclin D1 inhibition.
AB  - BACKGROUND: Farnesyltransferase inhibitors have the ability to interfere with
      various intracellular pathways, reducing cell survival and proliferation. They
      have become an attractive tool for cancer therapy, namely acute leukemias. In
      this work, we have studied the efficacy of alpha-hydroxyfarnesylphosphonic acid
      (alpha-HFPA) in CEM (acute T-cell lymphoblastic leukemia) in culture. MATERIALS
      AND METHODS: CEM cells were incubated with alpha-HFPA at different
      concentrations; viability and proliferation studies were performed using the
      trypan blue exclusion assay and cell morphological analysis. Expression of lamin
      A/C, cyclin D1 and BAD were analyzed by flow cytometry. RESULTS: Our results show
      that alpha-HFPA significantly decreases Farnesyltransferase activity, reduces
      cell proliferation and induces cell death through apoptosis in CEM cells, which
      is correlated with a reduction of cyclin D1 levels. CONCLUSION: This study
      suggests that alpha-HFPA blocks the cell cycle and induces cell death through
      apoptosis in CEM cells and may be a therapeutic approach in ALL.

PMID- 22399602
TI  - Interleukin-21 increases direct cytotoxicity and IFN-gamma production of ex vivo
      expanded NK cells towards breast cancer cells.
AB  - BACKGROUND/AIM: Interleukin-21(IL-21) stimulates cytotoxicity and interferon
      gamma (IFN-gamma) production in natural killer (NK) cells. However, little has
      been reported on the stimulatory effect of IL-21 on ex vivo expanded NK cells. In
      this study, we examined the cytotoxicity and IFN-gamma production of ex vivo
      expanded, IL-21-stimulated NK cells against trastuzumab-coated breast cancer
      cells. MATERIALS AND METHODS: To expand NK cells, peripheral blood mononuclear
      cells (PBMCs) were isolated and co-cultured with irradiated K562-mb15-41BBL cells
      in the presence of IL-2 and IL-15 for 3 weeks. After a 4-day stimulation with IL
      21, NK cell cytotoxicity and IFN-gamma production were measured. RESULTS: NK
      cells were expanded up to median of 911-fold and represented approximately 94.93%
      of expanded cells after 21 days. Cytotoxicity of the expanded NK cells against
      the MCF-7, SKBR3, and T47D cell lines was significantly increased following 4-day
      stimulation with IL-21. However, antibody-dependent cellular cytotoxicity
      mediated by trastruzumab was significantly increased only in the SKBR3 cell line,
      which highly expresses the HER2/neu antigen. IL-21 pre-treatment also increased
      IFN-gamma production in the expanded NK cells in response to the trastuzumab
      coated breast cancer cells. CONCLUSION: IL-21 significantly enhances the
      cytolytic activity and IFN-gamma production of ex vivo expanded NK cells in
      response to trastuzumab-coated breast cancer cells.

PMID- 22399603
TI  - Proteomic analysis of exosome-like vesicles derived from breast cancer cells.
AB  - BACKGROUND/AIM: The phenomenon of membrane vesicle-release by neoplastic cells is
      a growing field of interest in cancer research, due to their potential role in
      carrying a large array of tumor antigens when secreted into the extracellular
      medium. In particular, experimental evidence show that at least some of the tumor
      markers detected in the blood circulation of mammary carcinoma patients are
      carried by membrane-bound vesicles. Thus, biomarker research in breast cancer can
      gain great benefits from vesicle characterization. MATERIALS AND METHODS:
      Conditioned medium was collected from serum starved MDA-MB-231 sub-confluent cell
      cultures and exosome-like vesicles (ELVs) were isolated by ultracentrifugation.
      Ultrastructural analysis of ELVs was performed by transmission electron
      microscopy (TEM) and the purity of fraction was confirmed by western blotting
      assays. Proteomic profile of ELVs was carried out by 2 D-PAGE and protein
      identification performed by MALDI-ToF Mass Spectrometry. RESULTS: On the basis of
      ultrastructural and immunological characterization, the isolated vesicles have
      been classified as exosome-like vesicles (ELVs). The proteomic investigation
      showed a distinctive protein profile of the ELVs, in comparison to the whole cell
      lisates (WCL) proteome, which could be instrumental for cancer progression. The
      proteins were clustered into functional categories, according to the current
      bioinformatics resources and a Venn diagram was constructed based on these
      clusters. CONCLUSION: It is reasonable to assume that vesicle production allows
      neoplastic cells to exert different effects, according to the possible acceptor
      targets. For instance, vesicles could potentiate the malignant properties of
      adjacent neoplastic cells or activate non-tumoral cells. Moreover, vesicles could
      convey signals to immune cells and surrounding stroma cells. The present study
      may significantly contribute to the knowledge of the vesiculation phenomenon,
      which is a critical device for trans cellular communication in cancer.

PMID- 22399604
TI  - The expression of CD146 predicts a poor overall survival in patients with
      adenocarcinoma of the lung.
AB  - BACKGROUND: The epithelial-mesenchymal transition (EMT) is also involved in
      cancer progression and metastasis. The expression of mesenchymal marker genes
      might be associated with a more aggressive form of the disease. CD146 is a marker
      of mesenchymal cells, a potentially metastasis-promoting cell adhesion molecule,
      and its expression has been described in various types of solid tumors. We,
      herein, evaluated the expression of CD146 in patients with adenocarcinoma of the
      lung by using immunohistochemistry to clarify its clinical significance.
      MATERIALS AND METHODS: Tumor specimens were collected from 183 consecutive
      patients who underwent complete resection for lung adenocarcinoma from 2003 to
      2007 in our Department. We analyzed the CD146 expression levels in the primary
      lung adenocarcinoma by immunohistochemistry. RESULTS: Positive expression of
      CD146 was identified in 16 (8.7%) patients. A significant association was only
      observed between the CD146 expression level and male patient gender (p=0.03);
      other factors were not associated with CD146 expression. The 5-year overall
      survival (OS) rate in patients with tumors that were negative and positive for
      CD146 expression was 84.4% and 50.0%, respectively (p<0.01). A positive CD146
      expression was found to be associated with the OS based on a univariate survival
      analysis (p=0.013). CONCLUSION: CD146 expression was more frequently detected in
      males than in females. The positive expression of CD146 was associated with a
      poorer OS according to the survival analysis. CD146 may be a useful marker for
      predicting poor prognosis in patients with NSCLC following complete resection.

PMID- 22399605
TI  - SN-38 overcomes chemoresistance of colorectal cancer cells induced by hypoxia,
      through HIF1alpha.
AB  - BACKGROUND: Cancer cells can acquire resistance to therapy under hypoxic
      condition. We aimed to investigate the mechanisms regulating chemoresistance
      induced by hypoxia. MATERIALS AND METHODS: Human colorectal cancer cells, HT-29
      and SW480, were cultured under hypoxic conditions and the sensitivity to 5
      fluorouracil (FU), oxaliplatin, and SN-38 (active metabolite of irinotecan) was
      tested. The cell cycle was evaluated by flow cytometry after staining of cells
      with propidium iodide (PI). hypoxia-inducible factor 1alpha (HIF-1alpha)
      expression was evaluated by western blot analysis. RESULTS: Hypoxia induced
      strong G(0)/G(1) cell cycle arrest of cancer cells and abrogated the cytotoxic
      effects of 5-FU and oxaliplatin, but not that of SN-38. This effect was dependent
      on the significant inhibition of the accumulation of HIF-1alpha in cancer cells
      cultured under hypoxia by SN-38. Neither 5-FU nor oxaliplatin affected HIF-1alpha
      expression. CONCLUSION: SN-38, through inhibition of HIF-1alpha can overcome
      chemoresistance under hypoxic conditions of colon cancer cells.

PMID- 22399606
TI  - The role of canonical WNT signaling pathway in oral carcinogenesis: a
      comprehensive review.
AB  - Oral cancer is a common neoplasm worldwide. The incidence and mortality have also
      increased in recent decades. It is characterized by poor prognosis and a low
      survival rate despite sophisticated surgical and radiotherapeutic modalities. The
      WNTs comprise a large family of highly conserved growth factors associated with a
      number of functions. In this review, we focus largely on the canonical pathway,
      revealing the recent findings, in oral cancer research, thereby raising our
      understanding of the mechanisms of this crucial signaling in several cellular
      activities.

PMID- 22399607
TI  - Decreased levels of histone H3K9me1 indicate poor prognosis in patients with
      renal cell carcinoma.
AB  - BACKGROUND/AIM: To determine the role of global histone H3K9 and H4K20
      methylation levels as prognostic parameters in patients with renal cell cancer
      (RCC). MATERIAL AND METHODS: Global histone methylation levels were investigated
      in 193 RCC (including 142 clear cell (cc), 31 papillary (p), 10 chromophobe (ch)
      and 10 sarcomatoid (s) RCC), 10 oncocytomas and 30 benign renal specimens.
      RESULTS: Histone modifications were mostly similar in the different histological
      subtypes (p>0.05); significant differences were observed for ccRCC vs. pRCC and
      pRCC vs. sRCC. Comparing the global H3K9 methylation levels of benign renal
      tissue with RCC H3K9me1 (histone H3 lysine 9 mono-methylation) (p<0.001), H3K9me2
      (histone H3 lysine 9 di-methylation) (p=0.001) and H3K9me3 (histone H3 lysine 9
      tri-methylation) (p<0.001) was significantly over-expressed in benign renal
      tissue. H3K9 and H4K20 methylation levels were positively correlated to pT-stage
      (p<0.005) and grading (p<0.05). In localized RCC (n=144), H3K9me1 levels showed a
      significant correlation with progression-free survival in the univariate model
      (p=0.034). CONCLUSION: Global histone methylation levels may help to identify RCC
      patients with poor prognosis.

PMID- 22399608
TI  - Cytotoxicity of activated natural killer cells and expression of adhesion
      molecules in small-cell lung cancer.
AB  - BACKGROUND/AIM: Although small-cell lung cancer (SCLC) is sensitive to anticancer
      agents, most patients with SCLC experience relapse and die within two years.
      Here, we examined the relationship between natural killer (NK) cells and adhesion
      molecules on SCLC cell lines. MATERIALS AND METHODS: The expression levels of HLA
      class I, beta2-microglobulin, Fas/Apo-1 receptor (FAS) and adhesion molecules on
      SCLC cell lines were examined by flow cytometry. The cytotoxicity of activated NK
      cells from SCLC patients was examined using (51)Cr-release assay. RESULTS: HLA
      class I antigen and beta2-microglobulin expression levels in SCLC cell lines were
      lower than those in healthy volunteers. SCLC cell lines were susceptible to lysis
      by activated NK cells but this showed no correlation with expression levels of
      adhesion molecules. CONCLUSION: Target cell susceptibility to activated NK cells
      from five SCLC patients correlated with survival benefit; target cell
      susceptibility to activated NK cells may be a surrogate marker of outcome for
      patients with SCLC.

PMID- 22399610
TI  - Expression of cathepsin-D in primary breast cancer and corresponding local
      recurrence or metastasis: an immunohistochemical study.
AB  - BACKGROUND/AIM: The role of cathepsin-D is well established in breast cancer
      progression, being correlated with worse clinical outcomes. However, to our
      knowledge, no study has been performed investigating its expression in primary
      breast cancer tumors and their corresponding recurrences or metastasis. MATERIALS
      AND METHODS: Tissue sections from ten breast cancer cases and their corresponding
      local recurrences and six breast cancer cases and their corresponding metastases
      were immunohistochemically assessed for cathepsin-D reactivity. Cases diagnosed
      as either ductal carcinoma in situ (n=7), or breast carcinoma with no evidence of
      local recurrence or metastasis during follow-up (n=8) served as controls.
      RESULTS: Cathepsin-D was significantly up-regulated in all the study groups
      compared to controls. No difference was found between primary tumors and their
      corresponding recurrences or metastases. CONCLUSION: Cathepsin-D-expressing
      breast cancer cells seem to be involved in local recurrence or metastasis
      formation. Large series are needed to further verify this result with the aim of
      possible future molecular intervention.

PMID- 22399609
TI  - CSF-1R up-regulation is associated with response to pharmacotherapy targeting
      tyrosine kinase activity in AML cell lines.
AB  - BACKGROUND: The oncogenic potential of colony stimulating factor 1 receptor (CSF
      1R) has been well described, while its relevance for human acute myelogenous
      leukemia (AML) is still undetermined. In a recent clinical trial for AML,
      sunitinib was found to hold potential therapeutic benefit, however, the mechanism
      for this remains unknown. MATERIALS AND METHODS: In this study, we treated three
      myeloid cell lines, Mono-Mac 1, THP-1, and U937, with sunitinib, and a small
      molecule CSF-1R inhibitor (cFMS-I) to test the anticancer effect of such
      treatment. RESULTS: Mono-Mac 1 cells had inhibited proliferation and
      extracellular-signal regulated kinase activity as a result of CSF-1R inhibition
      and a dose-dependent increase in CSF-1R expression with both sunitinib and cFMS
      I. CONCLUSION: Our results suggest potential for CSF-1R as an important target of
      sunitinib or other similar drugs. Future study of CSF-1R may produce more
      targeted therapeutic approaches and aid in the development of personalized
      medicine for AML.

PMID- 22399611
TI  - Silencing of CCDC6 reduces the expression of 14-3-3sigma in colorectal carcinoma
      cells.
AB  - Coiled-coil domain containing 6 (CCDC6) is frequently rearranged in papillary
      thyroid carcinomas participating in the formation of RET/PTC1 oncogene. Other
      rearrangements involving CCDC6 have also been identified demonstrating its high
      susceptibility to chromosomal recombination. Malignancies bearing CCDC6 fusion
      genes are developed in a background where CCDC6 is either lost or deregulated.
      Our aim was to identify interacting proteins which are affected by the silencing
      of CCDC6 expression and could possibly link CCDC6 deregulation to cancer
      causality. Therefore, a proteomic approach was adopted using a human cancer cell
      line (HCT116) where CCDC6 expression was silenced by lentiviral shRNA constructs.
      14-3-3sigma down-regulation in the absence of CCDC6 was revealed and verified by
      western blot analysis and confocal microscopy. Only the levels and not the
      topology of CCDC6 were altered. The down-regulation of 14-3-3sigma in the absence
      of CCDC6 demonstrated their direct association and supports the notion that CCDC6
      contributes to cancer development, possibly through malignant pathways involving
      14-3-3sigma.

PMID- 22399612
TI  - Impact of temperature on cell death in a cell-culture model of hepatocellular
      carcinoma.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is one treatment option for
      hepatocellular carcinoma (HCC) where tumour cells are destroyed by heat. However,
      there is lack of knowledge about cellular reactions after heating. Therefore, we
      studied cell death after heat application in a cell-culture setting mimicking
      HCC. MATERIALS AND METHODS: Intracellularly stained hepatic stellate cells (LX-1)
      and HCC cells (HepG2) were cultivated in co-culture or alone. Apoptosis was
      determined by flow cytometry using AnnexinV-PE and eFluor(r)450. RESULTS: Heating
      resulted in early apoptosis for 20-30% of HepG2 cells and 10-15% of LX-1 cells.
      Late apoptosis was observed in a large percentage of cells 24 h after heating at
      65 degrees C for 15 min or 75 degrees C for 5 min; 65 degrees C for 10 min
      resulted in a moderate increase and 55 degrees C for 15 min resulted in a minor
      percentage of late apoptotic cells. CONCLUSION: Heat-treated LX-1 and HepG2 cells
      die by apoptosis. This finding is important for future planning tools to
      ameliorate RFA outcome in clinic.

PMID- 22399613
TI  - Diagnostic relevance of overexpressions of PKC-theta and DOG-1 and KIT/PDGFRA
      gene mutations in extragastrointestinal stromal tumors: a Korean six-centers
      study of 28 cases.
AB  - BACKGROUND: We investigated the clinicopathological and immunohistochemical
      characteristics, genetic aberrations and prognostic factors in 28 patients with
      extragastrointestinal stromal tumors (EGISTs) from six centers in South Korea.
      PATIENTS AND METHODS: Immunohistochemistry was performed for c-KIT (CD117), PKC
      theta (protein kinase C theta), DOG-1 (discovered on GIST-1), CD34, alpha-smooth
      muscle actin (alpha-SMA), vimentin, desmin and S-100 protein. Genetic analyses
      for the KIT gene (exon 9, 11, 13 and 17) and the platelet-derived growth factor
      receptor alpha (PDGFRA) gene (exons 12 and 18) were performed by direct
      sequencing of PCR products. The relationships of various clinicopathological
      characteristics and outcomes were also examined. RESULTS: Of the tumor samples,
      78.6% (22/28) were located in the intra-abdominal cavity including the omentum
      and mesentery, and 10.7% (3/28) were located in the retroperitoneum. All patients
      were older than 39 years. The median size of the tumors was 10 cm for the maximum
      diameter. When first detected, 57.1% of EGISTs were large in size, measuring more
      than 10 cm. Tumors that were larger than 10 cm were found more frequently among
      tumors with more than 10 mitoses per 50 high-power fields (HPFs) and this finding
      was statistically significant (p<0.05). Based on immunohistochemical results, the
      EGISTs were positive for c-KIT in 96.4% (27/28) of samples, PKC-theta in 82.1%
      (23/28), DOG-1 in 85.7% (24/28), PDGFRA in 82.1% (23/28), CD34 in 67.9% (19/28),
      vimentin in 100% (28/28), alpha-SMA in 28.6% (8/28), S-100 protein in 39.3%
      (11/28) and desmin in 28.6% (8/28). c-KIT, DOG-1 and PKC-theta immunostains were
      sensitive and specific, but the PDGFRA stain was not specific for EGISTs. c-KIT
      expression was correlated with DOG-1 expression (p<0.05). One c-KIT-negative
      EGIST was also negative for DOG-1, but positive for PDGFRA and PKC-theta
      immunostains. Out of all EGISTs, 57.1% had tumor necrosis and most of these were
      more than 10 cm in size, and had obvious nuclear atypia and high mitotic counts
      (>10/50 HPFs). Overall survival (OS) was correlated with tumor size >10 cm, tumor
      necrosis, obvious nuclear atypia, mitotic counts >10/50 HPFs and epithelioid or
      mixed cell type (p<0.05). Eleven EGISTs (44.0%) had mutations in the KIT gene and
      6 (24.0%) had mutations in the PDGFRA gene, the most common being missense
      mutations or deletions affecting exon 11 of the KIT gene (n=9) or exon 18 of the
      PDGFRA gene (n=6). Three cases showed co-existence of both KIT and PDGFRA gene
      mutations. There were no mutations of exon 17 of KIT and exon 12 of PDGFRA genes.
      CONCLUSION: The c-KIT, PKC-theta and DOG-1 antigens are the most sensitive and
      specific immunomarkers for confirming EGISTs. PKC-theta and PDGFRA immunostains
      are helpful markers for c-KIT-negative EGISTs. Survival analyses indicated that
      tumor size >10 cm, mitotic rate >10/50 HPFs, tumor necrosis, obvious nuclear
      atypia, and epithelioid or mixed cell type were significant predictors of
      survival. We found that the combination of these parameters helped to predict
      aggressive tumor behavior and may be useful for predicting the prognosis of
      EGISTs. The majority of gene mutations were identified in exon 11 of the KIT gene
      or exon 18 of the PDGFRA gene. The pattern of KIT and PDGFRA mutations in EGISTs
      was essentially similar to the one in GISTs. From the immunohistochemistry and
      molecular genetics perspective, EGISTs may be a special subtype of GISTs. Both
      immunohistochemical and molecular evaluation are useful for classifying tumors as
      EGISTs.

PMID- 22399614
TI  - Cisplatin with capecitabine: tolerance and activity in a phase I/II study
      preferentially enrolling patients with gastric cancer.
AB  - BACKGROUND: Capecitabine is an oral prodrug of flurouracil with broad activity
      against various malignancies. We explored its tolerance and preliminary efficacy
      when given together with cisplatin in a phase I/II study preferentially enrolling
      gastric cancer patients. PATIENTS AND METHODS: The study was a 3+3 dose
      escalation design and at the recommended phase II dose it included an expanded
      cohort of patients with upper gastrointestinal cancer. The dose of cisplatin was
      escalated from 40 to 50 mg/m(2) on day 1, and capecitabine of 2,500 mg/m(2)/day
      starting on day 2, was escalated from 5 days to 10 and then to 14 days, with the
      cycle repeated every 21 days. Prolonged maintenance with capecitabine was offered
      to selected patients completing three to six cycles. RESULTS: A total of 34
      patients were enrolled, and 27 patients were also evaluable for response. Dose
      limiting toxicities were palmar plantar erythrodyesthesia (PPE) and diarrhea;
      grade 3 and 4 neutropenia occurred in 8.8% and grade 3 PPE in 5.9%, while the
      most common grade 1-2 toxicities were anemia, neutropenia, fatigue and PPE (11.7%
      each). There were no treatment related deaths. With cisplatin at 40-50 mg/m(2)
      day 1 and capecitabine at 2,500 mg/m(2)/day for 5 -14 days every 21 days, 18
      patients with gastric cancer were treated and 7 had partial responses.
      CONCLUSION: A regimen of capecitabine and cisplatin at the doses and schedules
      explored was safe and active in patients with gastric cancer. Moreover, a 6-month
      administration of adjuvant capecitabine proved feasible, yielding favorable
      results after treatment completion and surgery, and should be investigated
      further.

PMID- 22399615
TI  - Is surgical trauma prometastatic?
AB  - A review of the literature is made on animal models showing that surgical trauma
      can facilitate the metastatic spread of experimental tumours. Whilst clinical
      evidence is often lacking, except controversial results for blood transfusion,
      several rodent models provided proof that operative stress, peritoneal trauma and
      hepatectomy create conditions which facilitate cancer metastasis. Moreover, it
      seems that mechanisms through which the metastatic process can be enhanced
      include inflammation, angiogenesis, secretion of growth factors and
      immunosuppression. Animal models do have limitations and the clinical translation
      is difficult. However, these models suggest that molecular mediators induced by
      surgical trauma can enhance metastasis. These molecules, already identified in
      surgical patients, could be inhibited with already available drugs. Appropriate
      controlled clinical studies covering the perioperative period should be designed.

PMID- 22399617
TI  - Integrated genomic characterization of the kallikrein gene locus in cancer.
AB  - BACKGROUND: The kallikrein-related peptidases (KLKs) have been implicated in many
      types of cancer, including prostate and ovarian. MATERIALS AND METHODS: We
      performed a comprehensive in silico study to characterize the KLK locus using
      transcriptomic (gene expression) and genomic (mutations and DNA copy number) data
      in prostate cancer (n=194), serous ovarian cancer (n=506), glioblastoma
      multiforme (n=206), and sarcoma (n=207) from The Cancer Genome Atlas and
      independent publicly available datasets to assess KLKs as cancer biomarkers.
      RESULTS: Overall, there was mRNA overexpression in prostate and serous ovarian
      cancer and decreased expression in glioblastoma multiforme. There was higher
      frequency of genomic loss in serous ovarian cancer, and rare KLK gene mutations
      observed in serous ovarian cancer and GBM. Dysregulation of KLKs correlates with
      survival: for prostate cancer, a combination of dysregulation of KLK1, 5 and 13
      was associated with worse disease-free survival. CONCLUSION: We conclude that
      specific dysregulation of KLKs at the genetic and transcriptomic levels have
      useful prognostic value.

PMID- 22399616
TI  - Biweekly docetaxel is better tolerated than conventional three-weekly dosing for
      advanced hormone-refractory prostate cancer.
AB  - BACKGROUND: Docetaxel administered every three weeks is the standard treatment
      for advanced hormone-refractory prostate cancer (HRPC). However, biweekly
      administration might be better tolerated due to the reduced peak drug
      concentrations. Therefore, we compared biweekly to triweekly docetaxel as first-
      or second-line chemotherapy for advanced HRPC in this prospective randomized
      multicenter trial. PATIENTS AND METHODS: In this study, 360 patients were
      randomly allocated to receive docetaxel 75 mg/m(2) i.v. d1 q3 weeks (tT) or 50
      mg/m(2) i.v. d1 and d 14, q4 weeks (bT) from March 2004 to May 2009. Oral
      prednisolone (10 mg/day) was administered in both groups. The groups were well
      balanced according to the WHO performance status in terms of mean age (70 vs. 68,
      range 45-87 years) and median serum PSA level at the time of study entry (109 vs.
      98 MUg/l, range 11-1490 MUg/l). The primary endpoint was time to treatment
      failure (TTF). ClinicalTrials.gov study identifier: NCT00255606. RESULTS:
      Ultimately, 158 patients (tT=79; bT=79) were included in this preplanned interim
      safety analysis; 567 and 487 cycles (equivalent to 1701 and 1948 weeks of
      treatment) were administered in the tT and bT groups, respectively. The most
      common grade 3-4 adverse events (expressed as %/cycles) in tT /bT were
      neutropenia 20%/14%; infection with/without neutropenia 8%/3%; fatigue 3%/3%;
      febrile neutropenia 2%/1%; and bone pain 2%/1%. Serious adverse events occurred
      more frequently in the group tT (n=60, 10.6% of cycles) than in the group bT
      (n=29, 6.0%, p=0.012). One patient died due to coronary infarction, and another
      was diagnosed with acute lymphocytic leukemia (both in the bT group). Thirty
      patients (38%) in the bT group and 22 patients (28%) in the tT group were still
      receiving treatment at 6 months (p=0.176). CONCLUSION: Biweekly docetaxel was
      tolerated better than conventional triweekly with fewer serious adverse events
      and more patients were still on the therapy at 6 months. Biweekly docetaxel
      therapy might be considered as an option for elderly patients exhibiting a
      compromised general condition.

PMID- 22399618
TI  - Small cell osteosarcoma successfully treated by high-dose ifosfamide and
      methotrexate, combined with carboplatin and pirarubicin.
AB  - Small cell osteosarcoma (SCO) is the most rare subtype of osteosarcoma and has a
      poor prognosis. An 11-year-old boy presented with 2-month history of painful
      tumefaction in the lower leg. Imaging analysis demonstrated a mixture of
      osteolytic and osteosclerotic lesions in the proximal tibia and extraskeletal
      area. Histology of the open biopsy showed small round cells producing mucous
      matrix. Based on these findings, SCO was suspected. The patient received three
      cycles of neoadjuvant chemotherapy using high-dose ifosfamide, high-dose
      methotrexate, pirarubicin and carboplatin. Wide-margin resection was performed
      followed by tibial lengthening using the Ilizarov method and two cycles of
      adjuvant chemotherapy with the same drugs as for neoadjuvant chemotherapy.
      Histology of the resected specimen showed that almost all tumor cells were
      necrotized. Neither recurrence nor metastasis was found after 4 years. Our
      experience suggests that neoadjuvant chemotherapy, such as the one used here,
      would be exceedingly effective for SCO without serious non-hematological
      toxicities.

PMID- 22399619
TI  - Phase I study of sunitinib plus modified FOLFOX6 in Japanese patients with
      treatment-naive colorectal cancer.
AB  - AIM: This phase I study evaluated sunitinib plus modified FOLFOX6 (mFOLFOX6: 5
      fluorouracil, leucovorin and oxaliplatin) in Japanese patients with treatment
      naive metastatic colorectal cancer. PATIENTS AND METHODS: Sunitinib was
      administered orally (37.5 mg/day, 4 weeks on, 2 weeks off [Schedule 4/2; arm A]
      or 50 mg/day, 2 weeks on, 2 weeks off [Schedule 2/2; arm B]) with mFOLFOX6.
      RESULTS: In arms A/B, respectively (n=6 each): median relative dose intensity was
      50.4%/89.1% for sunitinib and 39.2-69.8%/73.0-80.5% for mFOLFOX6 components. Most
      adverse events were grade 1/2. The most frequent grade 3/4 adverse events were
      neutropenia, thrombocytopenia, and leukopenia. No significant drug-drug
      interactions were detected. Four patients had objective responses in each arm.
      CONCLUSION: Sunitinib plus mFOLFOX6 had acceptable tolerability, with the
      Schedule 2/2 combination being generally more manageable than the Schedule 4/2.
      Based on two global trials and the present study, sunitinib on Schedule 2/2
      combined with chemotherapy may be considered, if further first-line trials are
      planned.

PMID- 22399620
TI  - Vitamin D and pancreatic cancer risk - no U-shaped curve.
AB  - In a recent paper entitled "Circulating 25-Hydroxyvitamin D and the Risk of
      Pancreatic Cancer," Stolzenberg-Solomon et al. reported that the odds ratio for
      diagnosis of pancreatic cancer shows a "statistically significant" precipitous
      jump of more than a factor of 2 at the highest presented concentrations of >100
      nmol/l. This was one of six related studies of the relation of 25-hydroxyvitamin
      D and six types of rarer cancers, collected by the Vitamin D Pooling Project
      (VDPP). An alternative analysis of the presented data suggests that the reported
      two-fold higher risk at the highest serum 25(OH)D level in the pancreatic cancer
      study is most likely a statistical artifact associated with the chosen cut-off
      point groupings and there is no U-shaped curve to be explained.

PMID- 22399621
TI  - Simultaneous multianalyte immunoassay measurement of five serum tumor markers in
      the detection of colorectal cancer.
AB  - Several serum tumor markers (STMs) have been proposed for the diagnosis of
      colorectal cancer (CRC), but their detection should be combined to increase
      accuracy. The measurement of a serum biomarker panel may improve the diagnostic
      value of single STM and a multianalyte immunoassay approach can shorten assay
      time and lower sample consumption. The aim of this study was to determine whether
      the simultaneous multianalyte immunoassay is useful for early detection of CRC.
      We measured a panel of five STMs namely, carcinoembryonic antigen (CEA), cancer
      antigen (CA) 19-9 and 72-4, cytokeratin fragment (CYFRA) 21-1, and osteopontin,
      in a selected homogeneous population of 102 consecutive patients (median age 66
      years, range 42-75 years) with Dukes B, G1-2, colorectal adenocarcinoma (cases)
      and in a group of 99 age- and sex-matched patients suffering from confirmed
      benign colorectal diseases (controls). Overall, 141 (70.1%) men and 60 (29.9%)
      women were studied. The highest sensitivity was 45.1% (osteopontin), while the
      highest specificity was 90.9% (CEA). The accuracy was lower, ranging from 24.9%
      (CA 19-9) to 67.2% (CEA). CYFRA 21-1 and CA 72-4 had similar sensitivity (35.3%
      and 31.4%, respectively), but a significantly different specificity (37.4% vs.
      89.9%). A combination of the five markers achieved 74.1% sensitivity and 94.3%
      specificity. In conclusion, in patients with CRC all single STMs show low
      sensitivity and specificity, while the simultaneous measurement of a panel of
      STMs may increase the diagnostic accuracy. When the sample volume is limited, the
      multianalyte immunoassay can be a reliable tool for studying patients undergoing
      laboratory screening for CRC.

PMID- 22399622
TI  - Modulation of systemic and intestinal immune response by interleukin-2 therapy in
      gastrointestinal surgical oncology. Personal experience in the context of current
      knowledge and future perspectives.
AB  - Interactions between host and malignant tumor is currently under intensive
      investigation. The immune system seems to have a key role in cancer development
      and spread. Novel strategies to actively modulate the immune system have been
      proposed to improve the outcome of disease in patients with neoplasms. Our
      experience with systemic immunomodulation by interleukin-2 (IL-2) focused on both
      systemic and local immunity in surgical gastrointestinal cancer. Preoperative IL
      2 subcutaneous injection was effective in counteracting postoperative
      immunosuppression, with a reduction of serum levels of IL-6 and the maintenance
      of preoperative levels of IL-12, a higher number of circulating total
      lymphocytes, and CD3(+) and CD4(+) T-cells, and a smaller decrease in circulating
      mature and immature dendritic cells (DCs), as well as a reduction in
      postoperative serum levels of vascular endothelial growth factor. At the
      intestinal level, in patients with colorectal cancer, preoperative administration
      of IL-2 affected both phenotype and function of resident dendritic cells and T
      cells, skewing local immunity toward a more immunogenic one. Our data showed that
      immunomodulation by IL-2 was effective in counteracting the systemic
      postoperative immune suppression related to surgical stress. IL-2 was also active
      at a local level on intestinal immunity, affecting both phenotype and function of
      resident T-cells and DCs. Future studies will encompass the possibility of
      reaching more adequate intratumoral IL-2 concentrations by direct intralesional
      injection to maximize immunostimulatory effects and minimize adverse effects.

PMID- 22399623
TI  - Immunotherapy approaches targeting regulatory T-cells.
AB  - The immune system prevents establishment and progression of cancer through innate
      and adaptive surveillance. However, some cancerous cells successfully evade the
      immune system. Regulatory T-cells (Tregs) facilitate such evasion. Tregs may be
      the factor responsible for the limited success of human tumor immunotherapy to
      date. To improve immunotherapy, it is thought that the number of Tregs and their
      functions should be inhibited in patients with advanced cancer. In this review,
      we focus on recent immunotherapy efforts targeting Tregs.

PMID- 22399624
TI  - Chemoprevention of asbestos-linked cancers: a systematic review.
AB  - Asbestos has been used extensively and, in spite of many countries having banned
      most of its uses, professional, domestic and environmental exposure has not
      ceased worldwide. Inhaled asbestos fibers can lead to malignant mesothelioma,
      lung cancer and non-cancerous conditions, while the substance persists
      indefinitely in the lung and pleural tissue, resulting in continuous damage.
      Exposed individuals may be offered medical surveillance or compensation, but
      nothing is currently being done to lower their specific cancer risk:
      chemoprevention seems a promising approach. A web search and a PubMed review of
      the literature on chemoprevention trials in individuals exposed to asbestos have
      been conducted. Forty-six articles on five projects were found and newly reviewed
      but, surprisingly, no novel trials have been set up for twenty years, although
      considerable advances have been gained in cancer chemoprevention. A re
      consideration of possibilities offered by chemoprevention should be encouraged.
      New trials based on the most recently characterized molecules should be planned,
      taking into account specific issues such as the need for a very large number of
      participants and a long follow up or, alternatively, the use of biomarkers as
      surrogate endpoints. The long latency of asbestos related diseases may offer
      delayed intervention opportunities. The lack of chemoprevention trials for
      asbestos exposure highlights the urgent need for research in this field.

PMID- 22399625
TI  - Association of DNA double-strand break gene XRCC6 genotypes and lung cancer in
      Taiwan.
AB  - AIM: The DNA repair gene X-ray repair complementing defective repair in Chinese
      hamster cells 6 (XRCC6) is thought to play an important role in the repair of DNA
      double-strand breaks. It is known that defects in double-strand break repair
      capacity can lead to irreversible genomic instability. However, the association
      of polymorphic variants of XRCC6 with lung cancer susceptibility has never been
      reported. In this hospital-based case-control study, the association of XRCC6
      promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter G-31A
      (rs132770), and intron 3 (rs132774) polymorphisms with lung cancer risk in a
      Taiwanese population, was studied. MATERIALS AND METHODS: In total, 358 patients
      with lung cancer and 716 healthy controls recruited from the China Medical
      Hospital in Taiwan were genotyped. RESULTS: The results showed that there were
      significant differences between lung cancer and control groups in the
      distribution of their genotypic (p=3.7*10(-4)) and allelic frequency (p=2.7*10(
      5)) in the XRCC6 promoter T-991C polymorphism. Individuals who carried at least
      one C allele (TC or CC) had a 2.03-fold increased odds ratio of developing lung
      cancer compared to those who carried the wild-type TT genotype (95% conference
      internal=1.42-2.91, p=0.0001). For the other three polymorphisms, there was no
      difference between the case and control groups in the distribution of either
      genotypic or allelic frequency. CONCLUSION: In conclusion, the XRCC6 promoter T
      991C, but not the promoter C-57G, promoter G-31A or intron 3, is associated with
      lung cancer susceptibility.

PMID- 22399626
TI  - Soluble human leukocyte antigen-G expression in patients with ductal and lobular
      breast malignancy.
AB  - BACKGROUND: Human leukocyte antigen-G (HLA-G) has been closely associated with
      diagnosis and prognosis in many types of human cancer. The current study aims to
      investigate soluble (s) HLA-G expression in patients with breast malignancy.
      PATIENTS AND METHODS: sHLA-G plasma expression was determined in 120 patients
      with breast cancer and 40 healthy controls using enzyme-linked immunosorbent
      assay. RESULTS: Plasma sHLA-G levels were significantly higher in breast cancer
      patients compared to healthy controls (p<0.001), with an area under the receiver
      operating characteristic (ROC) curve of 0.735 (95% Confidence interval=0.630
      0.841, p<0.001). Significantly increased sHLA-G expression was detected in
      patients with mixed type of coexisting ductal and lobular breast lesions,
      compared to patients with pure ductal carcinoma or pure lobular neoplasia
      (p<0.05). CONCLUSION: sHLA-G expression is closely associated with the
      histological type of breast cancer. Our findings support the application of sHLA
      G as a potential biomarker in body fluids for preoperative breast cancer
      detection and diagnosis.

PMID- 22399627
TI  - Phase II study of panobinostat and bortezomib in patients with pancreatic cancer
      progressing on gemcitabine-based therapy.
AB  - BACKGROUND: This single-arm, phase II study was designed to determine the
      efficacy and safety of panobinostat and bortezomib in patients with advanced
      pancreatic cancer. PATIENTS AND METHODS: Patients had to have a histological
      diagnosis of pancreatic cancer and progression on a standard gemcitabine-based
      therapy. Treatment cycles consisted of 21 days, with bortezomib given twice
      weekly at 1.3 mg/m(2) and panobinostat three times weekly at 20 mg during the
      first two weeks, followed by a 9-day rest period. RESULTS: Seven patients (3
      female, 4 male) were treated with at least one cycle, but the study was suspended
      after the enrollment of these patients because of a complete lack of treatment
      responses and early treatment-related toxicity. Median progression-free survival
      was 2.1 months (95% Confidence interval: 1.7-2.3 months). The most common grade 3
      or 4 adverse events were thrombocytopenia (57%) and diarrhea (29%). CONCLUSION:
      Treatment of advanced pancreatic cancer with bortezomib in combination with
      panobinostat is not supported by our clinical study.

PMID- 22399628
TI  - Sentinel lymphadenectomy compared to extended lymphadenectomy in men with
      prostate cancer undergoing prostatectomy.
AB  - BACKGROUND: To evaluate the reliability of sentinel lymphadenectomy compared to
      extended lymphadenectomy in men undergoing radical prostatectomy (RP). PATIENTS
      AND METHODS: A consecutive cohort of men with intermediate- to high-risk prostate
      cancer underwent RP with sentinel LA with intraoperative frozen section. In
      addition, extended LA was carried out in all cases. The endpoint was lymph node
      positivity. RESULTS: In total, 54 men with a mean age of 65.3 (50.9-75.6) years
      were analyzed. The mean preoperative prostate-specific antigen was 10.6 (2.8
      66.5) ng/ml, mean number of disease-positive cores was 5.8 (1-13), digital rectal
      examination was positive in 29 men (53.7%). In 12 men (22.2%), a positive lymph
      node was found (pN1). sLA was positive in 11 cases. One patient had a positive
      lymph node in eLA not found with sLA. The positive predictive value of frozen
      section was 50%; the respective figure for sLA compared to eLA was 91.6%.
      CONCLUSION: In this cohort, revealing a high prevalence of disease-positive lymph
      nodes, sLA was a reliable technique with a low rate of false negativity.

PMID- 22399629
TI  - Progestin treatment of atypical hyperplasia and well-differentiated
      adenocarcinoma of the endometrium to preserve fertility.
AB  - AIM: To evaluate the outcome of a cohort of young women treated with progestin
      for fertility-sparing management of endometrial atypical hyperplasia (AH) and
      endometrial carcinoma (EC). This retrospective multicentre cohort study included
      women under the age of 40 years treated conservatively for AH and EC to preserve
      fertility using progestin for at least 3 months. Four inclusion criteria were
      defined: (i) the presence of AH or grade 1 EC confirmed by two pathologists
      (including a reference pathologist); (ii) the use of conservative management for
      fertility sparing; (iii) adequate radiological examination before conservative
      management; and (iv) a minimal follow-up time of one year. RESULTS: Twenty-two
      patients fulfilled the inclusion criteria (8 had EC, and 14 had AH). After
      progestin treatment, 17 patients responded. Among the 17 patients who experienced
      remission, three also experienced disease relapse. One patient initially
      diagnosed with AH experienced progression of her disease to stage IIIA EC. Ten
      pregnancies were achieved in eight patients. CONCLUSION: Fertility-sparing
      management using progestin offers the opportunity to fulfil maternal desires in
      young patients diagnosed with AH and EC. However, progression of the disease is
      possible and close follow-up is needed.

PMID- 22399630
TI  - Combined oral topotecan plus carboplatin in relapsed or advanced cervical cancer:
      a GINECO phase I-II trial.
AB  - AIM: Combined cisplatin-topotecan therapy is standard care for advanced cervical
      cancer, however it is associated with haematotoxicity and nephrotoxicity. This
      trial was designed to assess the combination of carboplatin which is less
      nephrotoxic, and oral topotecan. PATIENTS AND METHODS: Patients with
      advanced/recurrent squamous cervical cancer received carboplatin (AUC5) on day 1,
      with escalating oral topotecan (3.0 mg/m(2) starting dose) on days 1, 8 and 15,
      every 4 weeks. Endpoints were the maximal tolerated dose for the phase I part and
      safety profiles and response rates for the phase II part of the study. RESULTS:
      Two dose levels were evaluated. A total of 18 patients (6 phase I, 12 phase II)
      were treated. The maximal tolerated dose was 3.0 mg/m(2) topotecan with
      carboplatin AUC5. Phase II accrual was interrupted following unacceptable
      toxicity, with 10 therapy-related related serious events in 9 out of 12 patients:
      grade 3-4 pancytopenia (7), febrile neutropenia (1), grade 3 haemorrhage (1) and
      grade 3 vomiting (1). CONCLUSION: Weekly oral topotecan combined with carboplatin
      is associated with unmanageable toxicity and is not recommended. Future studies
      are warranted to better understand the toxicity of such a combination and explore
      alternative combinations for advanced cervical cancer.

PMID- 22399631
TI  - Intraoperative ultrasound: improved resection rates in breast-conserving surgery.
AB  - AIM: The objective of this study was the investigation of a possible improvement
      of tumor resection rate, i.e. R0 vs. R1 resection when intraoperative ultrasound
      evaluation of tissue margins is used during breast-conserving surgery (BCS).
      PATIENTS AND METHODS: A total of 250 cases were evaluated retrospectively. The
      impact of ultrasound analysis onto clean margin rates was evaluated. A subgroup
      analysis assessed histology, stage, and neoadjuvant therapy with respect to R0
      resection rate and ultrasound evaluation. RESULTS: Of 250 BCS cases 84, (33.6%)
      underwent intraoperative ultrasound and 166 (66.4%) did not. Clean primary
      surgical margins (R0) were demonstrated for 218 (87.2%) patients after
      histological analysis. R0 resection was achieved in 81 (96.4%) patients in the
      ultrasound group compared to 137 (82.5%) in the control group. The difference
      between the two groups is significant. CONCLUSION: This study revealed a
      significant increase in R0 resection rates when intraoperative ultrasound was
      used to evaluate surgical margins.

PMID- 22399632
TI  - Coxsackie adenovirus receptor expression in carcinomas of the head and neck.
AB  - BACKGROUND: Advanced stage head and neck squamous cell carcinomas (HNSCC) have a
      poor prognosis, this being particularly true for undifferentiated carcinomas.
      Adenoviral oncolytic therapy, whose success depends on the expression of the
      coxsackie adenovirus receptor (CAR) on tumour cells, might be an interesting
      therapeutic option. Thus CAR expression in HNSCC was evaluated in the current
      study. PATIENTS AND METHODS: CAR expression in 41 cases of HNSCC was investigated
      immunohistochemically. RESULTS: CAR expression was very heterogeneous and was
      more abundant in well differentiated carcinomas than in less differentiated ones.
      Expression decreased from 72.4% in G1 tumours to 56% in G4 tumours. CONCLUSION:
      As CAR expression decreases during malignant progression in HNSCC, its down
      regulation in advanced grades of HNSCC is potential indicator of tumour
      progression. With regard to oncolytic therapy, CAR expression analysis should be
      performed prior to adenoviral oncolytic treatment to stratify patients for
      treatment.

PMID- 22399633
TI  - Serum antioxidant capacity and oxidative injury to pulmonary DNA in never-smokers
      with primary lung cancer.
AB  - BACKGROUND/AIM: Recently, in spite of the decrease in smoking in developed
      nations, the prevalence of primary lung cancer has been increasing in never
      smokers. In the present study, we examined the status of oxidative stress and
      attempted to clarify the influence of oxidative stress in non-smoking patients
      with lung cancer. PATIENTS AND METHODS: Sixty-one lung cancer patients who
      underwent a surgical resection, including 27 never-smokers and 34 ever-smokers
      with a history of more than 20 pack-years, were included. In addition, 18
      surgical patients with benign lung diseases treated during the same period were
      also included as non-malignant controls. Using blood samples, both serum
      oxidative stress (OS) and anti-oxidant capacity (AOC) were examined with the
      derivatives of reactive oxygen metabolites (D-Roms) test and the biological
      antioxidant power (BAP) test, respectively. To assess the oxidative damage of the
      DNA in lung tissues, the non-lesion site tissues of the lung were
      immunohistochemically examined for the accumulation of thymidine glycol (TG).
      RESULTS: There was no significant relationship between the serum OS level and
      various clinicopathological factors including the patient age, sex, body mass
      index, pathologic stage, and smoking status. On the other hand, the mean level of
      AOC was significantly lower in never-smokers than in ever-smokers. Although the
      mean TG-positive rate in ever-smokers was significantly higher than that in never
      smokers, the mean TG-positive rate of the latter was significantly higher than
      that of patients with benign diseases. CONCLUSION: The present study first
      demonstrated the low AOC in never-smokers with NSCLC, which may be a factor
      contributing to excessive oxidative DNA damage in the lung tissues.

PMID- 22399634
TI  - Peritoneal carcinomatosis from solid pseudopapillary neoplasm (Frantz's tumour)
      of the pancreas treated with HIPEC.
AB  - Solid pseudopapillary neoplasm (SPN) is a rare malignant tumour accounting for
      0.1% to 2.7% of all pancreatic neoplasms and affecting young women. Peritoneal
      carcinomatosis (PC) is even rarer, with only 11 reported cases. We describe a
      twelfth case occurring 13 years after the resection of an SPN which ruptured
      peroperatively. This 35-year-old woman had first undergone complete cytoreductive
      surgery (CCRS) alone and disease had relapsed within 8 months. Ultimately,
      further CCRS was combined with hyperthermic intraperitoneal chemotherapy (HIPEC)
      with oxaliplatin and irinotecan. The patient is now alive and disease free 31
      months after her last operation. In the literature, the surgical treatment of PC
      from an SPN has yielded disappointing results, with a 58% recurrence rate at
      intervals ranging from 1 to 19 years. As none of these patients developed distant
      metastases, indicating a strictly peritoneal disease, HIPEC might be a solution
      for preventing such recurrences.

PMID- 22399635
TI  - Cystic teratoma of the pancreas.
AB  - AIM: Benign cystic teratoma of the pancreas often appears to be potentially
      malignant in preoperative staging. The final diagnosis is generally obtained
      after surgical removal. Reliable prediction is mandatory for differential
      treatment. MATERIALS AND METHODS: A Medline query was performed for the terms
      cystic teratoma, dermoid cyst and pancreas. Data were analyzed for patient
      characteristics, clinical appearance, diagnostic findings, therapy and follow-up.
      RESULTS: Including our own, 26 cases of pancreatic cystic teratoma were
      identified. The majority of patients were symptomatic by unspecific
      gastrointestinal complaints. Up to date, imaging techniques fail at a distinct
      preoperative diagnosis. Surgical treatment evolved from various drainage and
      excision procedures into radical resection. CONCLUSION: Despite the strictly
      benign nature of cystic teratoma, oncologic resection is mostly inevitable due to
      difficult preoperative diagnosis. No reliable predictive marker was found to
      allow for organ- or parenchyma-preserving procedures. Therefore, surgery remains
      the treatment of choice to exclude malignancy.

PMID- 22399636
TI  - WT1 peptide therapy for a patient with chemotherapy-resistant salivary gland
      cancer.
AB  - Wilms' tumor (WT1) protein is one of the most promising target antigens for
      cancer immunotherapy. In fact, clinical responses, such as growth stabilization
      or shrinkage of tumor with immunological responses, have been reported in
      patients vaccinated with WT1 peptide. Here, we performed WT1 peptide-based
      immunotherapy for a patient with chemotherapy-resistant salivary gland cancer,
      whose histologic type was carcinoma ex pleomorphic adenoma. The patient with its
      pulmonary metastasis, refractory to chemotherapy, was intradermally injected with
      3 mg of WT1 peptide emulsified with Montanide ISA51 adjuvant at one-week
      intervals for 12 weeks. The considerably rapid growth of tumor was inhibited
      after WT1 vaccination, and stable disease, lasting three months, was achieved.
      Concomitantly, immunological responses, i.e. an increase in frequencies of WT1
      tetramer(+) CD8(+)T cells and delayed type hypersensitivity response, were
      detected after the vaccination. These results indicate the potential of WT1
      peptide-based immunotherapy for the treatment of chemotherapy-resistant salivery
      gland cancer.

PMID- 22399637
TI  - Repeat transrectal ultrasound biopsies with additional targeted cores according
      to results of functional prostate MRI detects high-risk prostate cancer in
      patients with previous negative biopsy and increased PSA - a pilot study.
AB  - BACKGROUND/AIM: Patients with previous negative transrectal ultrasound-guided
      biopsy (TRUS-GB) and persistently increased prostate-specific antigen (PSA) value
      represent a great diagnostic problem. Magnetic resonance imaging (MRI)-guided
      biopsy demonstrates high prostate cancer detection rates in these patients if
      functional MRI is suspicious for prostate cancer. However, MRI-guided biopsy is
      not commonly available and features considerable technical requirements. This was
      a pilot study to investigate if a standard repeat TRUS-GB, with additional
      targeted cores to suspicious lesions on functional MRI, can achieve similar
      detection rates as compared to MRI-guided biopsy. PATIENTS AND METHODS: 3 Tesla
      functional MRI was performed in 58 patients with >=1 previous negative biopsy,
      persistently increased PSA >=4 ng/ml and unsuspicious digital rectal examination.
      Suspicious lesions were marked on a localization map to enable their finding on
      TRUS. Random TRUS-GB with additional targeted cores according to the functional
      MRI findings were performed in patients with >=1 suspicious lesion. RESULTS: In
      37.9% (22/58), functional MRI demonstrated suspicious findings. Out of these 22
      patients, 16 underwent TRUS-GB with additional targeted cores. Prostate cancer
      was diagnosed in 68.8% (11/16). Eight out of these 11 patients subsequently
      underwent radical prostatectomy and all tumors fulfilled criteria for high-risk
      prostate cancer. With a median follow-up of 49.1 weeks neither significant PSA
      increase nor prostate cancer was detected in patients with normal functional MRI
      findings. CONCLUSION: Our approach enables excellent detection rates of
      clinically significant prostate cancer in patients with >=1 previous negative
      biopsy and persistently increased PSA levels. Due to the current disadvantages of
      MRI-guided biopsy, our approach therefore represents an excellent alternative to
      MRI-guided biopsy.

PMID- 22399638
TI  - Association of cyclin D1 genotypes with nasopharyngeal carcinoma risk.
AB  - AIM: The cell cycle regulator cyclin D1 (CCND1) is a critical regulator of the
      G1/S phase transition and plays an important part in several tumor types. This
      study aimed at investigating the association of CCND1 with and examining the
      interaction among CCND1 genotype and individual smoking habit in nasopharyngeal
      carcinoma susceptibility. PATIENTS AND METHODS: A total of 352 native Taiwanese
      consisting of 176 cases and 176 controls were enrolled in this hospital-based
      study, and CCND1 A870G (rs9344) and C1722G (rs678653) genotyping were analyzed by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and
      partially verified by direct sequencing. RESULTS: The results showed that there
      were significant differences between nasopharyngeal carcinoma and control groups
      in the distribution of the genotypic (p=0.0222) and allelic (p=0.0322)
      frequencies in the CCND1 A870G genotype. Individuals who carried at least one G
      allele (GG or AG) had a 0.71-fold lower risk of developing nasopharyngeal
      carcinoma compared to those who had the AA genotype (95% confidence interval=0.53
      0.96). In addition, there is an obvious joint effect of CCND1 A870G genotype with
      smoking habit on nasopharyngeal carcinoma susceptibility. CONCLUSION: These
      findings support the conclusion that the cell cycle regulation may play a role in
      nasopharyngeal carcinoma development and that CCND1 A870G polymorphism maybe a
      useful biomarker for nasopharyngeal carcinoma progression.

PMID- 22399639
TI  - Twice-daily dosing of temozolomide in combination with fotemustine for the
      treatment of patients with refractory glioblastoma.
AB  - Alkylating agents, such as temozolomide (TMZ) and fotemustine (FTM) are widely
      used in recurrent glioblastoma (GBM) regimes. Several strategies have been
      proposed to prevent resistance to these agents, by combining or sequencing them.
      We report the results of a pilot study of patients with refractory GBM receiving
      a regime of twice-daily dosing of temozolomide administered on day 1, (with an
      initial oral dose of 200 mg/m(2) and a second oral dose of 75 mg/m(2) 12 h
      later), followed by fotemustine in a single i.v. infusion at 75 mg/m(2) on day 2,
      repeated every four weeks. Enrolment was stopped at 15 patients due to lack of
      effectiveness of this schedule for patients with GBM. Toxicity was mild, with no
      grade 4 side effects reported. Results indicate that our temozolomide -FTM
      combined schedule is not effective, although well tolerated, in non responsive
      patients with GBM. Further strategies are required to improve the outcome of
      these patients.

PMID- 22399640
TI  - Interstitial lung disease associated with docetaxel in patients with advanced non
      small cell lung cancer.
AB  - BACKGROUND: Docetaxel is a well tolerated chemotherapy for non-small cell lung
      cancer (NSCLC). However, few studies have investigated interstitial lung disease
      (ILD) associated with docetaxel. The purpose is to describe the incidence of this
      complication by using NSCLC patients. PATIENTS AND METHODS: Between September
      2002 and March 2008, 392 patients with advanced NSCLC were treated with docetaxel
      and we retrospectively reviewed the radiography. In total, 18 patients
      subsequently developed ILD associated with docetaxel. RESULTS: The incidence of
      ILD associated with docetaxel was 4.6%. In treated patients who showed an
      interstitial change on chest computed tomography (CT), the incidence was very
      high (25.9%). Chest radiograph showed diffuse and bilateral ground-glass
      appearance patterns. CONCLUSION: Pre-existing interstitial change on CT was
      associated with a higher incidence of ILD (25.9%) among NSCLC patients treated
      with docetaxel. We don't recommend administering docetaxel for the patients with
      pre-existing interstitial change.

PMID- 22399641
TI  - Erlotinib treatment in patients with advanced lung adenocarcinoma with CISH
      positive and CISH-negative EGFR gene alterations.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) positivity as assessed by
      chromogenic in situ hybridization (CISH) has been demonstrated to be associated
      with EGFR mutation status. This study was conducted to compare the responsiveness
      of CISH-positive and CISH-negative lung adenocarcinomas to erlotinib. PATIENTS
      AND METHODS: Patients received erlotinib (150 mg/day) alone until disease
      progression or intolerable toxicity. EGFR gene status was examined by CISH. The
      response rate (RR), progression-free survival (PFS), overall survival (OS) and
      toxicity profiles were assessed. RESULTS: Thirty-one patients underwent response
      evaluations and CISH analyses, 12 of whom harboured CISH-positive
      adenocarcinomas. The overall RR (p=0.035), median PFS (p=0.091) and median OS
      (p=0.408) were higher in the CISH-positive group. No difference in toxicity
      profiles was observed between these two groups. CONCLUSION: EGFR status as
      assessed by CISH can predict the response to erlotinib in patients with advanced
      lung adenocarcinoma.

PMID- 22399642
TI  - No consistent relationship of glioblastoma incidence and cytomegalovirus
      seropositivity in whites, blacks, and Hispanics.
AB  - Glioblastoma multiforme is the most common and most aggressive type of primary
      brain tumor, accounting for 52% of all primary brain tumor cases and 20% of all
      intracranial tumors. Recently, evidence for a viral cause has been postulated,
      possibly cytomegalovirus (CMV). In one report, 80% of patients with newly
      diagnosed glioblastoma multiforme had detectable cytomegalovirus DNA in their
      peripheral blood, while sero-positive normal donors and other surgical patients
      did not exhibit detectable virus. However, another study reported that five
      glioblastoma patients showed no circulating CMV detected either with RT-PCR or
      blood culture. MATERIALS AND METHODS: We utilized Cytomegalovirus Seroprevalence
      in the United States data from the National Health and Nutrition Examination
      Surveys, 1988-2004. Glioblastoma Incidence Rates 2004-2008 by race and gender are
      from Cancer of the Brain and Other Nervous System - SEER Stat Fact Sheets
      (http://seer.cancer.gov/statfacts/html/brain.html). Statistical significance was
      determined from published 95% confidence intervals. RESULTS: CMV seroprevalence
      rates are not consistently related to glioblastoma incidence rates. CMV
      seroprevalence is significantly lower in whites than in blacks or Hispanics
      (Mexican Americans), while glioblastoma incidence is higher. However, both CMV
      seroprevalence and glioblastoma incidence are higher in Hispanics than in blacks.
      CMV seroprevalence rates are significantly higher in women, 55.5% (53.3-57.7,
      mean +/- 95% CI) than men, 45.2% (42.4-48.0), although glioblastoma is more
      common in men. CONCLUSION: A possible CMV-glioblastoma association cannot be
      readily substantiated with CMV seropositivity rates.

PMID- 22399646
TI  - Silencing of the Rac1 GTPase MtROP9 in Medicago truncatula stimulates early
      mycorrhizal and oomycete root colonizations but negatively affects rhizobial
      infection.
AB  - RAC/ROP proteins (rho-related GTPases of plants) are plant-specific small G
      proteins that function as molecular switches within elementary signal
      transduction pathways, including the regulation of reactive oxygen species (ROS)
      generation during early microbial infection via the activation of NADPH oxidase
      homologs of plants termed RBOH (for respiratory burst oxidase homolog). We
      investigated the role of Medicago truncatula Jemalong A17 small GTPase MtROP9,
      orthologous to Medicago sativa Rac1, via an RNA interference silencing approach.
      Composite M. truncatula plants (MtROP9i) whose roots have been transformed by
      Agrobacterium rhizogenes carrying the RNA interference vector were generated and
      infected with the symbiotic arbuscular mycorrhiza fungus Glomus intraradices and
      the rhizobial bacterium Sinorhizobium meliloti as well as with the pathogenic
      oomycete Aphanomyces euteiches. MtROP9i transgenic lines showed a clear growth
      reduced phenotype and revealed neither ROS generation nor MtROP9 and MtRBOH gene
      expression after microbial infection. Coincidently, antioxidative compounds were
      not induced in infected MtROP9i roots, as documented by differential proteomics
      (two-dimensional differential gel electrophoresis). Furthermore, MtROP9 knockdown
      clearly promoted mycorrhizal and A. euteiches early hyphal root colonization,
      while rhizobial infection was clearly impaired. Infected MtROP9i roots showed, in
      part, extremely swollen noninfected root hairs and reduced numbers of deformed
      nodules. S. meliloti nodulation factor treatments of MtROP9i led to deformed root
      hairs showing progressed swelling of its upper regions or even of the entire root
      hair and spontaneous constrictions but reduced branching effects occurring only
      at swollen root hairs. These results suggest a key role of Rac1 GTPase MtROP9 in
      ROS-mediated early infection signaling.

PMID- 22399647
TI  - The autoregulation gene SUNN mediates changes in root organ formation in response
      to nitrogen through alteration of shoot-to-root auxin transport.
AB  - We tested whether a gene regulating nodule number in Medicago truncatula, Super
      Numeric Nodules (SUNN ), is involved in root architecture responses to carbon (C)
      and nitrogen (N) and whether this is mediated by changes in shoot-to-root auxin
      transport. Nodules and lateral roots are root organs that are under the control
      of nutrient supply, but how their architecture is regulated in response to
      nutrients is unclear. We treated wild-type and sunn-1 seedlings with four
      combinations of low or increased N (as nitrate) and C (as CO(2)) and determined
      responses in C/N partitioning, plant growth, root and nodule density, and changes
      in auxin transport. In both genotypes, nodule density was negatively correlated
      with tissue N concentration, while only the wild type showed significant
      correlations between N concentration and lateral root density. Shoot-to-root
      auxin transport was negatively correlated with shoot N concentration in the wild
      type but not in the sunn-1 mutant. In addition, the ability of rhizobia to alter
      auxin transport depended on N and C treatment as well as the SUNN gene. Nodule
      and lateral root densities were negatively correlated with auxin transport in the
      wild type but not in the sunn-1 mutant. Our results suggest that SUNN is required
      for the modulation of shoot-to-root auxin transport in response to altered N
      tissue concentrations in the absence of rhizobia and that this controls lateral
      root density in response to N. The control of nodule density in response to N is
      more likely to occur locally in the root.

PMID- 22399648
TI  - How muscles function--the work loop technique.

PMID- 22399649
TI  - Climate change and cutaneous water loss of birds.
AB  - There is a crucial need to understand how physiological systems of animals will
      respond to increases in global air temperature. Water conservation may become
      more important for some species of birds, especially those living in deserts.
      Lipids of the stratum corneum (SC), the outer layer of the epidermis, create the
      barrier to water vapor diffusion, and thus control cutaneous water loss (CWL). An
      appreciation of the ability of birds to change CWL by altering lipids of the skin
      will be important to predict responses of birds to global warming. The
      interactions of these lipids are fundamental to the modulation of water loss
      through skin. Cerebrosides, with their hexose sugar moiety, are a key component
      of the SC in birds, but how these lipids interact with other lipids of the SC, or
      how they form hydrogen bonds with water molecules, to form a barrier to water
      vapor diffusion remains unknown. An understanding of how cerebrosides interact
      with other lipids of the SC, and of how the hydroxyl groups of cerebrosides
      interact with water molecules, may be a key to elucidating the control of CWL by
      the SC.

PMID- 22399650
TI  - Adaptation strategies to seasonal changes in environmental conditions of a
      domesticated horse breed, the Shetland pony (Equus ferus caballus).
AB  - Recent results suggest that the wild ancestor of the horse, the Przewalski horse,
      exhibits signs of a hypometabolism. However, there are speculations that domestic
      animals lost the ability to reduce energy expenditure during food shortage and
      adverse environmental conditions. Therefore, we investigated physiological and
      behavioural strategies employed by a robust domesticated horse breed, the
      Shetland pony, over the course of a year under temperate conditions by measuring
      ambient temperature (T(a)), subcutaneous temperature (T(s)), locomotor activity
      (LA), lying time, resting heart rate, body mass and body condition score. Ten
      animals were kept on pasture in summer and in open stables in winter; further, in
      winter the animals were allocated into one control and one feed-restricted group
      of five animals each to simulate natural seasonal food shortage. The annual
      course of the mean daily T(s) of all horses showed distinct fluctuations from a
      mean of 35.6+/-0.5 degrees C, with higher variations in summer than in winter.
      Diurnal amplitudes in T(s) were highest (P<0.001) in April (12.6 degrees C) and
      lowest in January (4.0 degrees C), with a nadir around dawn and a peak around mid
      day. The feed-restricted group had a significantly lower daily T(s) compared with
      the control group on cold winter days, with T(a) values below 0 degrees C. Mean
      annual heart rate and LA followed T(a) closely. Heart rate of the feed-restricted
      animals significantly decreased from a mean of 52.8+/-8.1 beats min(-1) in summer
      to 29+/-3.9 beats min(-1) in winter and differed from the control group
      (P<0.001). Mean daily LA was lowest at the end of winter (7000 activity impulses
      day(-1)) and highest in summer (25,000 activity impulses day(-1)). Our results
      show that Shetland ponies exhibit signs of a winter hypometabolism indicated by
      reduced heart rate and T(s). Thus, domesticated horses seem to have maintained
      the capacity for seasonal adaptation to environmental conditions by seasonal
      fluctuations in their metabolic rate.

PMID- 22399652
TI  - Octopamine improves learning in newly emerged bees but not in old foragers.
AB  - Honey bees (Apis mellifera) are well known for their excellent learning
      abilities. Although most age groups learn quickly to associate an odor with a
      sucrose reward, newly emerged bees and old foragers often perform poorly. For a
      long time, the reason for the poor learning performance of these age groups was
      unclear. We show that reduced sensitivity for sucrose is the cause for poor
      associative learning in newly emerged bees but not in old foragers. By increasing
      the sensitivity for sucrose through octopamine, we selectively improved the
      learning performance of insensitive newly emerged bees. Interestingly, the
      learning performance of foragers experiencing the same treatment remained low,
      despite the observed increase in sensitivity for the reward. We thus demonstrate
      that increasing sensitivity for the reward can improve the associative learning
      performance of bees when they are young but not when they had foraged for a long
      time. Importantly, octopamine can have very different effects on bees, depending
      on their initial sensory sensitivity. These differential effects of octopamine
      have important consequences for interpreting the action of biogenic amines on
      insect behavior.

PMID- 22399651
TI  - Allocation of endogenous and dietary protein in the reconstitution of the
      gastrointestinal tract in migratory blackcaps at stopover sites.
AB  - During migratory flight, the mass of the gastrointestinal tract (GIT) and its
      associated organs in small birds decreases in size by as much as 40%, compared
      with the preflight condition because of the catabolism of protein. At stopover
      sites, birds need 2-3 days to rebuild their GIT so that they can restore body
      mass and fat reserves to continue migration. The source of protein used to
      rebuild the GIT may be exogenous (from food ingested) or endogenous (reallocated
      from other organs) or both. Because the relative contribution of these sources to
      rebuild the GIT of migratory birds is not yet known, we mimicked in-flight
      fasting and then re-feeding in two groups of blackcaps (Sylvia atricapilla), a
      Palearctic migratory passerine. The birds were fed a diet containing either 3% or
      20% protein to simulate different refueling scenarios. During re-feeding, birds
      received known doses of (15)N-(l)-leucine before we measured the isotope
      concentrations in GIT and associated digestive organs and in locomotory muscles.
      We then quantified the extent to which blackcaps rebuilt their GIT with
      endogenous and/or dietary protein while refeeding after a fast. Our results
      indicate that blackcaps fed the low-protein diet incorporated less exogenous
      nitrogen into their tissues than birds fed the 20% protein diet. They also
      allocated relatively more exogenous protein to the GIT than to pectoral muscle
      than those birds re-fed with the high-protein diet. However, this compensation
      was not sufficient for birds eating the low-protein diet to rebuild their
      intestine at the same rate as the birds re-fed the high-protein diet. We
      concluded that blackcaps must choose stopover sites at which they can maximize
      protein intake to minimize the time it takes to rebuild their GIT and, thus,
      resume migration as soon as possible.

PMID- 22399653
TI  - Silk secretion from tarantula feet revisited: alleged spigots are probably
      chemoreceptors.
AB  - Controversial views have been expressed about whether tarantula feet can secrete
      fine silk threads that could prevent them from falling off smooth vertical
      surfaces. Two studies have claimed that 'ribbed hairs' on the tarsi of tarantulas
      produce silk. We examined these ribbed hairs in several tarantula species using
      light and scanning electron microscopy, and compared them with the silk-producing
      spigots on the abdominal spinnerets. We found that, morphologically, these ribbed
      hairs correspond very closely to known chemosensitive hairs in spiders; they have
      a distinct socket, a bent hair shaft with fine cuticular ridges, an eccentric
      double lumen within the hair shaft, and a blunt tip with a subterminal pore.
      Spigots on the spinnerets have a large bulbous base instead of a socket, a long
      shaft with a scaly surface and a central terminal pore. We never observed any
      silk threads coming out of these ribbed hairs under the electron microscope. By
      contrast, silk threads exiting the spigots on the spinnerets were common.
      Interestingly, ribbed hairs also occur on the spinnerets, often side by side with
      the silk-producing spigots. Our conclusion is that the ribbed hairs are
      chemoreceptors, not spigots. Observations of live tarantulas clinging inverted to
      glass coverslips confirmed that some substance is produced by the ribbed hairs,
      but it remains unclear whether this secretion is actually silk. In any case, the
      thousands of adhesive setae on the tarsi of legs and pedipalps almost certainly
      far outweigh any potential contribution from the sparsely distributed trails
      secreted by the ribbed hairs.

PMID- 22399654
TI  - Limited variation in visual sensitivity among bowerbird species suggests that
      there is no link between spectral tuning and variation in display colouration.
AB  - Variation in visual spectral tuning has evolved in concert with signal colour in
      some taxa, but there is limited evidence of this pattern in birds. To further
      investigate this possibility, we compared spectral sensitivity among bowerbird
      species that occupy different visual habitats and are highly diverged in plumage
      and decoration colour displays, which are important in mate choice and possibly
      reproductive isolation. Microspectrophotometry of violet-, short-, medium- and
      long-wavelength-sensitive cones revealed no significant interspecific variation
      in visual pigment peak spectral absorbance values that ranged between 404-410,
      454, 503-511 and 558-568 nm, respectively. Mean cut-off wavelength values for C-,
      Y-, R- and P-type coloured oil droplets were 418-441, 508-523, 558-573 and 412
      503 nm, respectively, with values at longer wavelengths in ventral compared with
      dorsal retina cones. Low ocular media mid-wavelength transmission values (340-352
      nm) suggest that bowerbirds may represent a transitional stage in the evolution
      from the ancestral violet-sensitive- to the derived ultraviolet-sensitive-type
      short-wavelength-sensitive-1-based visual system found in younger passerine
      lineages. Sequence data obtained for rod opsin and four cone opsin genes were
      identical at key tuning sites, except for an interspecific leucine-52-alanine
      polymorphism in the short-wavelength-sensitive 2 opsin. There was no obvious
      relationship between relative proportions of cone classes and either visual
      habitat or display colour. Overall, we detected little interspecific variation in
      bowerbird spectral sensitivity and no association between sensitivity and display
      diversity, which is consistent with the general trend among avian taxa.

PMID- 22399655
TI  - Proteomic responses of blue mussel (Mytilus) congeners to temperature
      acclimation.
AB  - The ability to acclimate to variable environmental conditions affects the
      biogeographic range of species, their success at colonizing new habitats, and
      their likelihood of surviving rapid anthropogenic climate change. Here we
      compared responses to temperature acclimation (4 weeks at 7, 13 and 19 degrees C)
      in gill tissue of the warm-adapted intertidal blue mussel Mytilus
      galloprovincialis, an invasive species in the northeastern Pacific, and the cold
      adapted M. trossulus, the native congener in the region, to better understand the
      physiological differences underlying the ongoing competition. Using two
      dimensional gel electrophoresis and tandem mass spectrometry, we showed that warm
      acclimation caused changes in cytoskeletal composition and proteins of energy
      metabolism in both species, consistent with increasing rates of filtration and
      respiration due to increased ciliary activity. During cold acclimation, changes
      in cytoskeletal proteins were accompanied by increasing abundances of oxidative
      stress proteins and molecular chaperones, possibly because of the increased
      production of aldehydes as indicated by the upregulation of aldehyde
      dehydrogenase. The cold-adapted M. trossulus showed increased abundances of
      molecular chaperones at 19 degrees C, but M. galloprovincialis did not,
      suggesting that the two species differ in their long-term upper thermal limits.
      In contrast, the warm-adapted M. galloprovincialis showed a stronger response to
      cold acclimation than M. trossulus, including changes in abundance in more
      proteins and differing protein expression profiles between 7 and 13 degrees C, a
      pattern absent in M. trossulus. In general, increasing levels of oxidative stress
      proteins inversely correlate with modifications in Krebs cycle and electron
      transport chain proteins, indicating a trade-off between oxidative stress
      resistance and energy production. Overall, our results help explain why M.
      galloprovincialis has replaced M. trossulus in southern California over the last
      century, but also suggest that M. trossulus may maintain a competitive advantage
      at colder temperatures. Anthropogenic global warming may reinforce the advantage
      M. galloprovincialis has over M. trossulus in the warmer parts of the latter's
      historical range.

PMID- 22399656
TI  - Effects of night-time warming on temperate ectotherm reproduction: potential
      fitness benefits of climate change for side-blotched lizards.
AB  - Temperate ectotherms, especially those at higher latitudes, are expected to
      benefit from climate warming, but few data yet exist to verify this prediction.
      Furthermore, most previous studies on the effects of climate change utilized a
      model of uniform annual change, which assumes that temperature increases are
      symmetric on diurnal or seasonal time scales. In this study, we simulated
      observed trends in the asymmetric alteration of diurnal temperature range by
      increasing night-time temperatures experienced by female lizards during their
      ovarian cycle as well as by the resulting eggs during their incubation. We found
      that higher night-time temperatures during the ovarian cycle increased the
      probability of reproductive success and decreased the duration of the
      reproductive cycle, but did not affect embryo stage or size at oviposition,
      clutch size, egg mass or relative clutch mass. Furthermore, higher incubation
      temperatures increased hatchling size and decreased incubation period but had no
      effect on incubation success. Subsequent hatchlings were more likely to survive
      winter if they hatched earlier, though our sample size of hatchlings was
      relatively small. These findings indicate that higher night-time temperatures
      mainly affect rate processes and that certain aspects of life history are less
      directly temperature dependent. As our findings confirm that climate warming is
      likely to increase the rate of development as well as advance reproductive
      phenology, we predict that warmer nights during the breeding season will increase
      reproductive output as well as subsequent survival in many temperate ectotherms,
      both of which should have positive fitness effects.

PMID- 22399657
TI  - Relationship between colouration and body condition in a crab spider that lures
      pollinators.
AB  - Sit-and-wait predators have evolved several traits that increase the probability
      of encountering prey, including lures that attract prey. Although most crab
      spiders (Thomisidae) are known by their ability to change colour in order to
      match the background, a few use a different strategy. They are UV-reflective,
      creating a colour contrast against UV-absorbing flowers that is attractive for
      pollinators. The nature of the relationship between colour contrast and foraging
      success is unknown, as is how spiders trade off the potential costs and benefits
      of strong colour contrast. Therefore, this study investigated the relationship
      between spider colouration, foraging success and background colouration in a crab
      spider species known to lure pollinators via UV reflectance (Thomisus
      spectabilis). Field data revealed that spider body condition - a proxy of past
      foraging success - is positively related to overall colour contrast. We
      experimentally tested the effect of satiation and background colour on spider
      colour change. Throughout the experiment, spiders changed their colour contrast
      regardless of their food intake, suggesting that colour contrast and the UV
      component contributing to overall contrast are not caused by spider condition.
      Although spiders responded to different backgrounds by subtly changing their body
      colour, this did not result in colour matching. We believe that the observed
      variation in colour contrast and hence conspicuousness in the field, coupled with
      the spiders' reaction to our manipulation, could be the result of plasticity in
      response to prey.

PMID- 22399658
TI  - Non-linear scaling of oxygen consumption and heart rate in a very large cockroach
      species (Gromphadorhina portentosa): correlated changes with body size and
      temperature.
AB  - Although well documented in vertebrates, correlated changes between metabolic
      rate and cardiovascular function of insects have rarely been described. Using the
      very large cockroach species Gromphadorhina portentosa, we examined oxygen
      consumption and heart rate across a range of body sizes and temperatures.
      Metabolic rate scaled positively and heart rate negatively with body size, but
      neither scaled linearly. The response of these two variables to temperature was
      similar. This correlated response to endogenous (body mass) and exogenous
      (temperature) variables is likely explained by a mutual dependence on similar
      metabolic substrate use and/or coupled regulatory pathways. The intraspecific
      scaling for oxygen consumption rate showed an apparent plateauing at body masses
      greater than about 3 g. An examination of cuticle mass across all instars
      revealed isometric scaling with no evidence of an ontogenetic shift towards
      proportionally larger cuticles. Published oxygen consumption rates of other
      Blattodea species were also examined and, as in our intraspecific examination of
      G. portentosa, the scaling relationship was found to be non-linear with a
      decreasing slope at larger body masses. The decreasing slope at very large body
      masses in both intraspecific and interspecific comparisons may have important
      implications for future investigations of the relationship between oxygen
      transport and maximum body size in insects.

PMID- 22399659
TI  - Corticosterone promotes emergence of fictive air breathing in Xenopus laevis
      Daudin tadpole brainstems.
AB  - The emergence of air breathing during amphibian metamorphosis requires
      significant changes to the brainstem circuits that generate and regulate
      breathing. However, the mechanisms controlling this developmental process are
      unknown. Because corticosterone plays an important role in the neuroendocrine
      regulation of amphibian metamorphosis, we tested the hypothesis that
      corticosterone augments fictive air breathing frequency in Xenopus laevis. To do
      so, we compared the fictive air breathing frequency produced by in vitro
      brainstem preparations from pre-metamorphic tadpoles and adult frogs before and
      after 1 h application of corticosterone (100 nmol l(-1)). Fictive breathing
      measurements related to gill and lung ventilation were recorded extracellularly
      from cranial nerve rootlets V and X. Corticosterone application had no immediate
      effect on respiratory-related motor output produced by brainstems from either
      developmental stage. One hour after corticosterone wash out, fictive lung
      ventilation frequency was increased whereas gill burst frequency was decreased.
      This effect was stage specific as it was significant only in preparations from
      tadpoles. GABA application (0.001-0.5 mmol l(-1)) augmented fictive air breathing
      in tadpole preparations. However, this effect of GABA was no longer observed
      following corticosterone treatment. An increase in circulating corticosterone is
      one of the endocrine processes that orchestrate central nervous system
      remodelling during metamorphosis. The age-specific effects of corticosterone
      application indicate that this hormone can act as an important regulator of
      respiratory control development in Xenopus tadpoles. Concurrent changes in
      GABAergic neurotransmission probably contribute to this maturation process,
      leading to the emergence of air breathing in this species.

PMID- 22399660
TI  - A buckling region in locust hindlegs contains resilin and absorbs energy when
      jumping or kicking goes wrong.
AB  - If a hindleg of a locust slips during jumping, or misses its target during
      kicking, energy generated by the two extensor tibiae muscles is no longer
      expended in raising the body or striking a target. How, then, is the energy in a
      jump (4100-4800 MUJ) or kick (1700 MUJ) dissipated? A specialised buckling region
      found in the proximal hind-tibia where the bending moment is high, but not
      present in the other legs, buckled and allowed the distal part of the tibia to
      extend. In jumps when a hindleg slipped, it bent by a mean of 23+/-14 deg at a
      velocity of 13.4+/-9.5 deg ms(-1); in kicks that failed to contact a target it
      bent by 32+/-16 deg at a velocity of 32.9+/-9.5 deg ms(-1). It also buckled 8.5+/
      4.0 deg at a rate of 0.063+/-0.005 deg ms(-1) when the tibia was prevented from
      flexing fully about the femur in preparation for both these movements. By
      experimentally buckling this region through 40 deg at velocities of 0.001-0.65
      deg ms(-1), we showed that one hindleg could store about 870 MUJ on bending, of
      which 210 MUJ was dissipated back to the leg on release. A band of blue
      fluorescence was revealed at the buckling region under UV illumination that had
      the two key signatures of the elastic protein resilin. A group of campaniform
      sensilla 300 MUm proximal to the buckling region responded to imposed buckling
      movements. The features of the buckling region show that it can act as a shock
      absorber as proposed previously when jumping and kicking movements go wrong.

PMID- 22399661
TI  - Expression of SERCA and phospholamban in rainbow trout (Oncorhynchus mykiss)
      heart: comparison of atrial and ventricular tissue and effects of thermal
      acclimation.
AB  - In the heart of rainbow trout (Oncorhynchus mykiss), the rate of contraction and
      Ca(2+) uptake into the sarcoplasmic reticulum (SR) are faster in atrial than
      ventricular muscle, and contraction force relies more on SR Ca(2+) stores after
      acclimation to cold. This study tested the hypothesis that differences in
      contractile properties and Ca(2+) regulation between atrial and ventricular
      muscle, and between warm-(WA) and cold-acclimated (CA) trout hearts, are
      associated with differences in expression of sarco(endo)plasmic reticulum Ca(2+)
      ATPase (SERCA) and/or phospholamban (PLN), an inhibitor of the cardiac SERCA.
      Quantitative PCR (SERCA only) and antibodies raised against SERCA and PLN were
      used to determine abundances of SERCA2 transcripts and SERCA and PLN proteins,
      respectively, in atrium and ventricle of trout acclimated to cold (+4 degrees C,
      CA) and warm (+18 degrees C, WA) temperatures. Expression of SERCA2 transcripts
      was 1.6 and 2.1 times higher in atrium than ventricle of WA and CA trout,
      respectively (P<0.05). At the protein level, differences in SERCA expression
      between atrium and ventricle were 6.1- and 23-fold for WA and CA trout,
      respectively (P<0.001). Acclimation to cold increased SERCA2 transcripts 2.6- and
      2.0-fold in atrial and ventricular muscle, respectively (P<0.05). At the protein
      level, cold-induced elevation of SERCA (4.6-fold) was noted only in atrial
      (P<0.05) but not in ventricular tissue (P>0.05). The expression pattern of PLN
      was similar to that of the SERCA protein, but chamber-specific and temperature
      induced differences were much smaller than in the case of SERCA. In the
      ventricle, PLN/SERCA ratio was 2.1 and 7.0 times higher than in the atrium for WA
      and CA fish, respectively. These findings are consistent with the hypothesis that
      low PLN/SERCA ratio in atrial tissue enables faster SR Ca(2+) reuptake and thus
      contributes to faster kinetics of contraction in comparison with ventricular
      muscle. Similarly, cold-induced decrease in PLN/SERCA ratio may be associated
      with faster contraction kinetics of the CA trout heart, in particular in the
      atrial muscle.

PMID- 22399662
TI  - Cutaneous water loss and covalently bound lipids of the stratum corneum in
      nestling house sparrows (Passer domesticus L.) from desert and mesic habitats.
AB  - Lipids of the stratum corneum (SC), the outer layer of the epidermis of birds and
      mammals, provide a barrier to water vapor diffusion through the skin. The SC of
      birds consists of flat dead cells, called corneocytes, and two lipid
      compartments: an intercellular matrix and a monolayer of covalently bound lipids
      (CBLs) attached to the outer surface of the corneocytes. We previously found two
      classes of sphingolipids, ceramides and cerebrosides, covalently bound to
      corneocytes in the SC of house sparrows (Passer domesticus L.); these lipids were
      associated with cutaneous water loss (CWL). In this study, we collected adult and
      nestling house sparrows from Ohio and nestlings from Saudi Arabia, acclimated
      them to either high or low humidity, and measured their rates of CWL. We also
      measured CWL for natural populations of nestlings from Ohio and Saudi Arabia,
      beginning when chicks were 2 days old until they fledged. We then evaluated the
      composition of the CBLs of the SC of sparrows using thin layer chromatography. We
      found that adult house sparrows had a greater diversity of CBLs in their SC than
      previously described. During ontogeny, nestling sparrows increased the amount of
      CBLs and developed their CBLs differently, depending on their habitat.
      Acclimating nestlings to different humidity regimes did not alter the ontogeny of
      the CBLs, suggesting that these lipids represent a fundamental component of SC
      organization that does not respond to short-term environmental change.

PMID- 22399663
TI  - Active uptake of artificial particles in the nematode Caenorhabditis elegans.
AB  - Feeding and food choice are crucial to the survival of an animal. The nematode
      Caenorhabditis elegans feeds on various microorganisms in nature, and is usually
      fed Escherichia coli in the laboratory. To elucidate the mechanisms of food/non
      food discrimination in C. elegans, we examined the accumulation of various
      fluorescent polystyrene microspheres in the absence and presence of bacterial
      food. In the absence of food and on agar plates, C. elegans worms actively
      accumulated 0.5 and 1 MUm diameter microspheres, whereas those microspheres <0.5
      MUm or >3 MUm were rarely accumulated. Carboxylate microspheres were accumulated
      more than sulfate or amine microspheres. These results of accumulation in the
      absence of food probably well simulate uptake of or feeding on the microspheres.
      Presence of food bacteria even at bacteria:nematode ratios of 1:100 or 1:10
      significantly reduced accumulation of 0.5 MUm microspheres, and accumulation was
      reduced to approximately one-fourth of that observed in the absence of bacteria
      at a ratio of 1:1. When accumulation of microspheres was examined with the
      chemical sense mutants che-2, tax-2, odr-1 and odr-2, or the feeding mutant eat
      1, all the mutants showed less accumulation than the wild type in the absence of
      food. In the presence of food, the che-2 mutant showed more accumulation than the
      wild type. It is possible that C. elegans discriminates food both physically,
      based on size, and chemically, based on taste and olfaction.

PMID- 22399664
TI  - The male blue crab, Callinectes sapidus, uses both chromatic and achromatic cues
      during mate choice.
AB  - In the blue crab, Callinectes sapidus, claw color varies by sex, sexual maturity
      and individual. Males rely in part on color cues to select appropriate mates, and
      these chromatic cues may be perceived through an opponent interaction between two
      photoreceptors with maximum wavelength sensitivities at 440 and 508 nm. The range
      of color discrimination of this dichromatic visual system may be limited,
      however, and it is unclear whether male blue crabs are capable of discriminating
      the natural variations in claw color that may be important in mate choice. By
      testing males' innate color preferences in binary choice tests between
      photographs of red-clawed females and six variations of orange-clawed females, we
      examined both the chromatic (opponent interaction) and achromatic (relative
      luminance) cues used in male mate choice. Males significantly preferred red
      clawed females to orange-clawed females, except when the test colors were similar
      in both opponency and relative luminance. Our results are unusual in that they
      indicate that male mate choice in the blue crab is not guided solely by
      achromatic or chromatic mechanisms, suggesting that both color and intensity are
      used to evaluate female claw color.

PMID- 22399665
TI  - Structural characterisation of the N-glycan moiety of the barnacle settlement
      inducing protein complex (SIPC).
AB  - Many barnacle species are gregarious and their cypris larvae display a remarkable
      ability to explore surfaces before committing to permanent attachment. The
      chemical cue to gregarious settlement behaviour - the settlement-inducing protein
      complex (SIPC) - is an alpha(2)-macroglobulin-like glycoprotein. This cuticular
      protein may also be involved in cyprid reversible adhesion if its presence is
      confirmed in footprints of adhesive deposited during exploratory behaviour, which
      increase the attractiveness of surfaces and signal other cyprids to settle. The
      full-length open-reading frame of the SIPC gene encodes a protein of 1547 amino
      acids with seven potential N-glycosylation sites. In this study on Balanus
      amphitrite, glycan profiling of the SIPC via hydrophilic interaction liquid
      chromatography with fluorescence detection (HILIC-fluorescence) provided evidence
      of predominantly high mannose glycans (M2-9), with the occurrence of
      monofucosylated oligomannose glycans (F(6)M2-4) in lower proportions. The high
      mannose glycosylation found supports previous observations of an interaction with
      mannose-binding lectins and exogenous mannose increasing settlement in B.
      amphitrite cypris larvae. Transmission electron microscopy of the deglycosylated
      SIPC revealed a multi-lobed globular protein with a diameter of ~8 nm. Obtaining
      a complete structural characterisation of the SIPC remains a goal that has the
      potential to inspire solutions to the age-old problem of barnacle fouling.

PMID- 22399667
TI  - Development of agonistic encounters in dominance hierarchy formation in juvenile
      crayfish.
AB  - We have characterized the behavioural patterns of crayfish during agonistic bouts
      between groups of crayfish of four different body lengths (9-19, 20-32, 41-48 and
      69-75 mm) to characterize changes in the patterns of agonistic encounter during
      development. The behaviour of both dominant and subordinate animals was analysed
      by single frame measurement of video recordings. Behavioural acts that occurred
      during agonistic bouts were categorized as one of seven types: capture, fight,
      contact, approach, retreat, tailflip and neutral. Dominant-subordinate
      relationships were formed between juvenile crayfish as early as the third stage
      of development. Patterns of agonistic bouts to determine social hierarchy became
      more aggressive during development. The dominant-subordinate relationship was
      usually determined after contact in crayfish of less than 20 mm and 20-32 mm in
      length, while several bouts of fights were necessary for crayfish of 41-48 and 69
      75 mm in length. Furthermore, social hierarchy was formed more rapidly in small
      crayfish. In larger animals, the number of approaches by dominant animals that
      promoted retreat in subordinate animals increased after the establishment of the
      winner-loser relationship. In smaller crayfish, in contrast, no measurable
      changes in these behaviour patterns were observed before and after the
      establishment of the winner-loser relationship. With increasing body size, the
      probability of tailflips decreased while that of retreats increased as the
      submissive behavioural act of subordinate animals.

PMID- 22399666
TI  - Comparative characterization of Na+ transport in Cyprinodon variegatus variegatus
      and Cyprinodon variegatus hubbsi: a model species complex for studying teleost
      invasion of freshwater.
AB  - The euryhaline fish Cyprinodon variegatus variegatus is capable of tolerating
      ambient salinities ranging from 0.3 to 160 PSU, but is incapable of long-term
      survival in freshwater (<2 mmol l(-1) Na(+)). A population isolated in several
      freshwater (0.4-1 mmol l(-1) Na(+)) lakes in central Florida is now designated as
      a subspecies (Cyprinodon variegatus hubbsi). We conducted a comparative study of
      Na(+) transport kinetics in these two populations when acclimated to different
      ambient Na(+) concentrations. Results reveal that the two subspecies have
      qualitatively similar low affinity Na(+) uptake kinetics (K(m)=7000-38,000 MUmol
      l(-1)) when acclimated to 2 or 7 mmol l(-1) Na(+), but C. v. hubbsi switches to a
      high affinity system (K(m)=100-140 MUmol l(-1)) in low-Na(+) freshwater (<=1 mmol
      l(-1) Na(+)). Inhibitor experiments indicate that Na(+) uptake in both subspecies
      is EIPA-sensitive, but sensitivity decreases with increasing external Na(+). EIPA
      induced a 95% inhibition of Na(+) influx in C. v. hubbsi acclimated to 0.1 mmol
      l(-1) Na(+), suggesting that this subspecies is utilizing a Na(+)/H(+) exchanger
      to take up Na(+) in low-Na(+) environments despite theoretical thermodynamic
      constraints. Na(+) uptake in C. v. hubbsi acclimated to 0.1 mmol l(-1) Na(+) is
      phenamil-sensitive but not bafilomycin-sensitive, leading to uncertainty about
      whether this subspecies also utilizes Na(+) channels for Na(+) uptake.
      Experiments with both subspecies acclimated to 7 mmol l(-1) Na(+) also indicate
      that a Cl(-)-dependent Na(+) uptake pathway is present. This pathway is not
      metolazone-sensitive (NCC inhibitor) in either species but is bumetanide
      sensitive in C. v. variegatus but not C. v. hubbsi. This suggests that an apical
      NKCC is increasingly involved with Na(+) uptake for this subspecies as external
      Na(+) increases. Finally, characterization of mitochondria-rich cell (MRC) size
      and density in fish acclimated to different ambient Na(+) concentrations revealed
      significant increases in the number and size of emergent MRCs with decreasing
      ambient Na(+). A linear relationship between the fractional area of emergent MRCs
      and Na(+) uptake rate was observed for both subspecies. However, C. v. variegatus
      have lower Na(+) uptake rates at a given MRC fractional area compared with C. v.
      hubbsi, indicating that the enhanced Na(+) uptake by C. v. hubbsi at low ambient
      Na(+) concentrations is not strictly a result of increased MRC fractional area,
      and other variables, such as differential expression of proteins involved in
      Na(+) uptake, must provide C. v. hubbsi with the ability to osmoregulate in
      dilute freshwater.

PMID- 22399669
TI  - Gearing for speed slows the predatory strike of a mantis shrimp.
AB  - The geometry of an animal's skeleton governs the transmission of force to its
      appendages. Joints and rigid elements that create a relatively large output
      displacement per unit input displacement have been considered to be geared for
      speed, but the relationship between skeletal geometry and speed is largely
      untested. The present study explored this subject with experiments and
      mathematical modeling to evaluate how morphological differences in the raptorial
      appendage of a mantis shrimp (Gonodactylus smithii) affect the speed of its
      predatory strike. Based on morphological measurements and material testing, we
      computationally simulated the transmission of the stored elastic energy that
      powers a strike and the drag that resists this motion. After verifying the
      model's predictions against measurements of strike impulse, we conducted a series
      of simulations that varied the linkage geometry, but were provided with a fixed
      amount of stored elastic energy. We found that a skeletal geometry that creates a
      large output displacement achieves a slower maximum speed of rotation than a low
      displacement system. This is because a large displacement by the appendage causes
      a relatively large proportion of its elastic energy to be lost to the generation
      of drag. Therefore, the efficiency of transmission from elastic to kinetic energy
      mediates the relationship between the geometry and the speed of a skeleton. We
      propose that transmission efficiency plays a similar role in form-function
      relationships for skeletal systems in a diversity of animals.

PMID- 22399668
TI  - CFTR is restricted to a small population of high expresser cells that provide a
      forskolin-sensitive transepithelial Cl- conductance in the proximal colon of the
      possum, Trichosurus vulpecula.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is central to
      anion secretion in both the possum and eutherian small intestine. Here, we
      investigated its role in the possum proximal colon, which has novel transport
      properties compared with the eutherian proximal colon. Despite considerable CFTR
      expression, high doses of the CFTR activator forskolin (EC(50)~10 MUmol l(-1))
      were required for a modest, CFTR-dependent increase in short-circuit current
      (I(sc)) in the proximal colon. Presumably, this is because CFTR is restricted to
      the apical membrane of a small population of CFTR high expresser (CHE) cells in
      the surface and upper crypt epithelium. Furthermore, although the forskolin
      stimulated I(sc) was dependent on serosal Na(+), Cl(-) and HCO(3)(-), consistent
      with anion secretion, inhibition of the basolateral Na-K-2Cl(-) (NKCC1) or Na
      HCO(3) (pNBCe1) cotransporters did not prevent it. Therefore, although NKCC1 and
      pNBCe1 are expressed in the colonic epithelium they do not appear to be expressed
      in CHE cells. At low doses (IC(50)~1 MUmol l(-1)), forskolin also decreased the
      transepithelial conductance (G(T)) of the colon through inhibition of a 4,4'
      diisothiocyano-2,2'-stilbenedisulphonic acid-sensitive anion conductance in the
      basolateral membrane of the CHE cells. This conductance is arranged in series
      with CFTR in the CHE cells and, therefore, the CHE cells provide a
      transepithelial Cl(-) conductance for passive Cl(-) absorption across the
      epithelium. Inhibition of the basolateral Cl(-) conductance of the CHE cells by
      forskolin will inhibit Na(+) absorption by restricting the movement of its
      counter-ion Cl(-), assisting in the conversion of the tissue from an absorptive
      to a secretory state.

PMID- 22399670
TI  - The impact of extent of resection and histological subtype on the outcome of
      adult patients with high-grade gliomas.
AB  - OBJECTIVE: We reviewed the relationship between extent of resection and survival
      of patients with high-grade gliomas with special consideration of an
      oligodendroglial component. METHODS: A retrospective review was performed on 160
      adult patients with histological diagnosis of high-grade gliomas since 2000. All
      histological slides were categorized as high-grade astrocytomas or
      oligodendroglial tumors. Extent of resection was assessed by early post-operative
      magnetic resonance imaging and classified as complete resection, incomplete
      resection and biopsy. Measured outcomes were overall survival and progression
      free survival. The independent association of extent of resection and survival
      was analyzed by the multivariate proportional hazard model adjusting for
      prognostic factors. RESULTS: The lesions were classified as high-grade
      astrocytomas in 93 patients and high-grade oligodendroglial tumors in 67
      patients. In high-grade astrocytomas, the median survival after complete
      resection (n = 36), incomplete resection (n = 36) and biopsy (n = 21) was 23.4,
      15.3 and 12.6 months, respectively. Complete resection was independently
      associated with increased overall survival (P < 0.001) and progression-free
      survival (P = 0.002) compared with incomplete resection, while incomplete
      resection was not associated with survival benefit compared with biopsy by
      multivariate analysis. On the other hand, in high-grade oligodendroglial tumors,
      the majority of patients were still alive and there is no significant difference
      in the survival between complete resection (n = 24) and incomplete resection (n =
      33), while even incomplete resection had a significantly longer overall survival
      (P < 0.001) and progression-free survival (P = 0.006) compared with biopsy (n =
      10). CONCLUSIONS: Maximal cytoreduction improves the survival of high-grade
      gliomas, although our data indicated that the impact of extent of resection in
      high-grade astrocytomas is different from that in high-grade oligodendroglial
      tumors.

PMID- 22399671
TI  - Cutaneous calcifications induced by heel pricks.

PMID- 22399672
TI  - The ethics of migration and healthcare.

PMID- 22399673
TI  - Children's experiences of dialysis: a systematic review of qualitative studies.
AB  - OBJECTIVE: To describe the experiences and perspectives of children and
      adolescents on dialysis. DESIGN: A systematic review of qualitative studies was
      conducted that explored the experiences of children on dialysis. Electronic
      databases and reference lists of relevant articles were searched to October Week
      2, 2010. RESULTS: A total of 17 studies, which reported the experiences of 143
      children receiving dialysis, were included. Five major themes were identified:
      loss of control (high reliance on carers, parental overprotectiveness,
      unrelenting dependence on a machine, impaired body integrity), restricted
      lifestyle (limited socialisation opportunities, academic struggle), coping
      strategies (hope for kidney transplant and medical advances, social support,
      positive determination and self-awareness, engaging in activities, denial),
      managing treatment (ownership, proactive involvement, adherence to fluid and diet
      restrictions) and feeling different (abnormal physical appearance, injustice,
      being a burden). CONCLUSIONS: Children undergoing dialysis experience impaired
      growth, invasive procedures, school and social constraints. They often have poor
      self-esteem and a pervasive sense of losing their identity, body integrity,
      control, independence and opportunity. Interventions are needed to equip children
      with the capacity to manage their health, participate in community, engage in
      'permissible' recreational activities, progress in their studies, and remain
      vigilant in dialysis and treatment responsibilities, for improved health and
      treatment outcomes.

PMID- 22399674
TI  - Little evidence that increased choice and competition in the English National
      Health Service will benefit children and young people.

PMID- 22399675
TI  - AntigenMap 3D: an online antigenic cartography resource.
AB  - SUMMARY: Antigenic cartography is a useful technique to visualize and minimize
      errors in immunological data by projecting antigens to 2D or 3D cartography.
      However, a 2D cartography may not be sufficient to capture the antigenic
      relationship from high-dimensional immunological data. AntigenMap 3D presents an
      online, interactive, and robust 3D antigenic cartography construction and
      visualization resource. AntigenMap 3D can be applied to identify antigenic
      variants and vaccine strain candidates for pathogens with rapid antigenic
      variations, such as influenza A virus. AVAILABILITY AND IMPLEMENTATION:
      http://sysbio.cvm.msstate.edu/AntigenMap3D

PMID- 22399677
TI  - Mirroring co-evolving trees in the light of their topologies.
AB  - MOTIVATION: Determining the interaction partners among protein/domain families
      poses hard computational problems, in particular in the presence of paralogous
      proteins. Available approaches aim to identify interaction partners among
      protein/domain families through maximizing the similarity between trimmed
      versions of their phylogenetic trees. Since maximization of any natural
      similarity score is computationally difficult, many approaches employ heuristics
      to evaluate the distance matrices corresponding to the tree topologies in
      question. In this article, we devise an efficient deterministic algorithm which
      directly maximizes the similarity between two leaf labeled trees with edge
      lengths, obtaining a score-optimal alignment of the two trees in question.
      RESULTS: Our algorithm is significantly faster than those methods based on
      distance matrix comparison: 1 min on a single processor versus 730 h on a
      supercomputer. Furthermore, we outperform the current state-of-the-art exhaustive
      search approach in terms of precision, while incurring acceptable losses in
      recall. AVAILABILITY: A C implementation of the method demonstrated in this
      article is available at http://compbio.cs.sfu.ca/mirrort.htm

PMID- 22399676
TI  - Evolutionary inaccuracy of pairwise structural alignments.
AB  - MOTIVATION: Structural alignment methods are widely used to generate gold
      standard alignments for improving multiple sequence alignments and transferring
      functional annotations, as well as for assigning structural distances between
      proteins. However, the correctness of the alignments generated by these methods
      is difficult to assess objectively since little is known about the exact
      evolutionary history of most proteins. Since homology is an equivalence relation,
      an upper bound on alignment quality can be found by assessing the consistency of
      alignments. Measuring the consistency of current methods of structure alignment
      and determining the causes of inconsistencies can, therefore, provide information
      on the quality of current methods and suggest possibilities for further
      improvement. RESULTS: We analyze the self-consistency of seven widely-used
      structural alignment methods (SAP, TM-align, Fr-TM-align, MAMMOTH, DALI, CE and
      FATCAT) on a diverse, non-redundant set of 1863 domains from the SCOP database
      and demonstrate that even for relatively similar proteins the degree of
      inconsistency of the alignments on a residue level is high (30%). We further show
      that levels of consistency vary substantially between methods, with two methods
      (SAP and Fr-TM-align) producing more consistent alignments than the rest.
      Inconsistency is found to be higher near gaps and for proteins of low structural
      complexity, as well as for helices. The ability of the methods to identify good
      structural alignments is also assessed using geometric measures, for which FATCAT
      (flexible mode) is found to be the best performer despite being highly
      inconsistent. We conclude that there is substantial scope for improving the
      consistency of structural alignment methods. CONTACT: msadows@nimr.mrc.ac.uk
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22399678
TI  - Bioimage informatics: a new category in Bioinformatics.

PMID- 22399680
TI  - A hindbrain-repressive Wnt3a/Meis3/Tsh1 circuit promotes neuronal differentiation
      and coordinates tissue maturation.
AB  - During development, early inducing programs must later be counterbalanced for
      coordinated tissue maturation. In Xenopus laevis embryos, activation of the Meis3
      transcription factor by a mesodermal Wnt3a signal lies at the core of the
      hindbrain developmental program. We now identify a hindbrain restricting circuit,
      surprisingly comprising the hindbrain inducers Wnt3a and Meis3, and Tsh1 protein.
      Functional and biochemical analyses show that upon Tsh1 induction by strong
      Wnt3a/Meis3 feedback loop activity, the Meis3-Tsh1 transcription complex
      represses the Meis3 promoter, allowing cell cycle exit and neuron
      differentiation. Meis3 protein exhibits a conserved dual-role in hindbrain
      development, both inducing neural progenitors and maintaining their proliferative
      state. In this regulatory circuit, the Tsh1 co-repressor controls transcription
      factor gene expression that modulates cell cycle exit, morphogenesis and
      differentiation, thus coordinating neural tissue maturation. This newly
      identified Wnt/Meis/Tsh circuit could play an important role in diverse
      developmental and disease processes.

PMID- 22399679
TI  - Context-dependent function of a conserved translational regulatory module.
AB  - The modification of transcriptional regulation is a well-documented evolutionary
      mechanism in both plants and animals, but post-transcriptional controls have
      received less attention. The derived hermaphrodite of C. elegans has regulated
      spermatogenesis in an otherwise female body. The PUF family RNA-binding proteins
      FBF-1 and FBF-2 limit XX spermatogenesis by repressing the male-promoting
      proteins FEM-3 and GLD-1. Here, we examine the function of PUF homologs from
      other Caenorhabditis species, with emphasis on C. briggsae, which evolved selfing
      convergently. C. briggsae lacks a bona fide fbf-1/2 ortholog, but two members of
      the related PUF-2 subfamily, Cbr-puf-2 and Cbr-puf-1.2, do have a redundant
      germline sex determination role. Surprisingly, this is to promote, rather than
      limit, hermaphrodite spermatogenesis. We provide genetic, molecular and
      biochemical evidence that Cbr-puf-2 and Cbr-puf-1.2 repress Cbr-gld-1 by a
      conserved mechanism. However, Cbr-gld-1 acts to limit, rather than promote, XX
      spermatogenesis. As with gld-1, no sex determination function for fbf or puf-2
      orthologs is observed in gonochoristic Caenorhabditis. These results indicate
      that PUF family genes were co-opted for sex determination in each hermaphrodite
      via their long-standing association with gld-1, and that their precise sex
      determining roles depend on the species-specific context in which they act.
      Finally, we document non-redundant roles for Cbr-puf-2 in embryonic and early
      larval development, the latter role being essential. Thus, recently duplicated
      PUF paralogs have already acquired distinct functions.

PMID- 22399683
TI  - Somatic small RNA pathways promote the mitotic events of megagametogenesis during
      female reproductive development in Arabidopsis.
AB  - Female gamete development in Arabidopsis ovules comprises two phases. During
      megasporogenesis, a somatic ovule cell differentiates into a megaspore mother
      cell and undergoes meiosis to produce four haploid megaspores, three of which
      degrade. The surviving functional megaspore participates in megagametogenesis,
      undergoing syncytial mitosis and cellular differentiation to produce a
      multicellular female gametophyte containing the egg and central cell, progenitors
      of the embryo and endosperm of the seed. The transition between megasporogenesis
      and megagametogenesis is poorly characterised, partly owing to the
      inaccessibility of reproductive cells within the ovule. Here, laser capture
      microdissection was used to identify genes expressed in and/or around developing
      megaspores during the transition to megagametogenesis. ARGONAUTE5 (AGO5), a
      putative effector of small RNA (sRNA) silencing pathways, was found to be
      expressed around reproductive cells during megasporogenesis, and a novel semi
      dominant ago5-4 insertion allele showed defects in the initiation of
      megagametogenesis. Expression of a viral RNAi suppressor, P1/Hc-Pro, driven by
      the WUSCHEL and AGO5 promoters in somatic cells flanking the megaspores resulted
      in a similar phenotype. This indicates that sRNA-dependent pathways acting in
      somatic ovule tissues promote the initiation of megagametogenesis in the
      functional megaspore. Notably, these pathways are independent of AGO9, which
      functions in somatic epidermal ovule cells to inhibit the formation of multiple
      megaspore-like cells. Therefore, one somatic sRNA pathway involving AGO9
      restricts reproductive development to the functional megaspore and a second
      pathway, inhibited by ago5-4 and P1/Hc-Pro, promotes megagametogenesis.

PMID- 22399682
TI  - Separating planar cell polarity and Hippo pathway activities of the
      protocadherins Fat and Dachsous.
AB  - The giant Drosophila protocadherin Fat (Ft) affects planar cell polarity (PCP).
      Ft also inhibits the overgrowth of imaginal discs via the Hippo pathway,
      repressing the activity of the transcription co-factor Yorkie (Yki). Much of Ft
      activity is likely to be mediated by its intracellular domain (Ft ICD). However,
      the links between the Ft ICD and either PCP or Hippo activity are poorly
      understood, and the role of the Hippo pathway in PCP is ambiguous. We have
      performed a structure-function analysis of the Ft ICD. We found that the effects
      of the Ft ICD on PCP and the Hippo pathway are largely separable. Surprisingly,
      the domains required for PCP and Hippo activities do not map to any of the
      previously identified protein interaction domains, nor, with one exception, to
      the regions that are highly conserved in mammalian Fat4. We also found that the
      extracellular domain of Ft can act independently of the Ft ICD in PCP and can
      trigger dominant-negative and boundary effects on Hippo activity, probably via
      binding to the protocadherin Dachsous.

PMID- 22399681
TI  - Motor axon exit from the mammalian spinal cord is controlled by the homeodomain
      protein Nkx2.9 via Robo-Slit signaling.
AB  - Mammalian motor circuits control voluntary movements by transmitting signals from
      the central nervous system (CNS) to muscle targets. To form these circuits, motor
      neurons (MNs) must extend their axons out of the CNS. Although exit from the CNS
      is an indispensable phase of motor axon pathfinding, the underlying molecular
      mechanisms remain obscure. Here, we present the first identification of a genetic
      pathway that regulates motor axon exit from the vertebrate spinal cord, utilizing
      spinal accessory motor neurons (SACMNs) as a model system. SACMNs are a
      homogeneous population of spinal MNs with axons that leave the CNS through a
      discrete lateral exit point (LEP) and can be visualized by the expression of the
      cell surface protein BEN. We show that the homeodomain transcription factor
      Nkx2.9 is selectively required for SACMN axon exit and identify the Robo2
      guidance receptor as a likely downstream effector of Nkx2.9; loss of Nkx2.9 leads
      to a reduction in Robo2 mRNA and protein within SACMNs and SACMN axons fail to
      exit the spinal cord in Robo2-deficient mice. Consistent with short-range
      interactions between Robo2 and Slit ligands regulating SACMN axon exit, Robo2
      expressing SACMN axons normally navigate through LEP-associated Slits as they
      emerge from the spinal cord, and fail to exit in Slit-deficient mice. Our studies
      support the view that Nkx2.9 controls SACMN axon exit from the mammalian spinal
      cord by regulating Robo-Slit signaling.

PMID- 22399684
TI  - Neurula rotation determines left-right asymmetry in ascidian tadpole larvae.
AB  - Tadpole larvae of the ascidian Halocynthia roretzi show morphological left-right
      asymmetry. The tail invariably bends towards the left side within the vitelline
      membrane. The structure of the larval brain is remarkably asymmetric. nodal, a
      conserved gene that shows left-sided expression, is also expressed on the left
      side in H. roretzi but in the epidermis unlike in vertebrates. We show that nodal
      signaling at the late neurula stage is required for stereotypic morphological
      left-right asymmetry at later stages. We uncover a novel mechanism to break
      embryonic symmetry, in which rotation of whole embryos provides the initial cue
      for left-sided expression of nodal. Two hours prior to the onset of nodal
      expression, the neurula embryo rotates along the anterior-posterior axis in a
      counterclockwise direction when seen in posterior view, and then this rotation
      stops when the left side of the embryo is oriented downwards. It is likely that
      epidermis monocilia, which appear at the neurula rotation stage, generate the
      driving force for the rotation. When the embryo lies on the left side, protrusion
      of the neural fold physically prevents it from rotating further. Experiments in
      which neurula rotation is perturbed by various means, including centrifugation
      and sandwiching between glass, indicate that contact of the left epidermis with
      the vitelline membrane as a consequence of neurula rotation promotes nodal
      expression in the left epidermis. We suggest that chemical, and not mechanical,
      signals from the vitelline membrane promote nodal expression. Neurula rotation is
      also conserved in other ascidian species.

PMID- 22399686
TI  - HDLs protect pancreatic beta-cells against ER stress by restoring protein folding
      and trafficking.
AB  - Endoplasmic reticulum (ER) homeostasis alteration contributes to pancreatic beta
      cell dysfunction and death and favors the development of diabetes. In this study,
      we demonstrate that HDLs protect beta-cells against ER stress induced by
      thapsigargin, cyclopiazonic acid, palmitate, insulin overexpression, and high
      glucose concentrations. ER stress marker induction and ER morphology disruption
      mediated by these stimuli were inhibited by HDLs. Using a temperature-sensitive
      viral glycoprotein folding mutant, we show that HDLs correct impaired protein
      trafficking and folding induced by thapsigargin and palmitate. The ability of
      HDLs to protect beta-cells against ER stress was inhibited by brefeldin A, an ER
      to Golgi trafficking blocker. These results indicate that HDLs restore ER
      homeostasis in response to ER stress, which is required for their ability to
      promote beta-cell survival. This study identifies a cellular mechanism mediating
      the beneficial effect of HDLs on beta-cells against ER stress-inducing factors.

PMID- 22399685
TI  - Xenopus Nanos1 is required to prevent endoderm gene expression and apoptosis in
      primordial germ cells.
AB  - Nanos is expressed in multipotent cells, stem cells and primordial germ cells
      (PGCs) of organisms as diverse as jellyfish and humans. It functions together
      with Pumilio to translationally repress targeted mRNAs. Here we show by loss-of
      function experiments that Xenopus Nanos1 is required to preserve PGC fate.
      Morpholino knockdown of maternal Nanos1 resulted in a striking decrease in PGCs
      and a loss of germ cells from the gonads. Lineage tracing and TUNEL staining
      reveal that Nanos1-deficient PGCs fail to migrate out of the endoderm. They
      appear to undergo apoptosis rather than convert to normal endoderm. Whereas
      normal PGCs do not become transcriptionally active until neurula, Nanos1-depleted
      PGCs prematurely exhibit a hyperphosphorylated RNA polymerase II C-terminal
      domain at the midblastula transition. Furthermore, they inappropriately express
      somatic genes characteristic of endoderm regulated by maternal VegT, including
      Xsox17alpha, Bix4, Mixer, GATA4 and Edd. We further demonstrate that Pumilio
      specifically binds VegT RNA in vitro and represses, along with Nanos1, VegT
      translation within PGCs. Repressed VegT RNA in wild-type PGCs is significantly
      less stable than VegT in Nanos1-depleted PGCs. Our data indicate that maternal
      VegT RNA is an authentic target of Nanos1/Pumilio translational repression. We
      propose that Nanos1 functions to translationally repress RNAs that normally
      specify endoderm and promote apoptosis, thus preserving the germline.

PMID- 22399687
TI  - The distinct ophthalmic phenotype of Knobloch syndrome in children.
AB  - BACKGROUND: Knobloch syndrome is defined as a triad of occipital defect, high
      myopia and vitreo-retinal degeneration (often with later retinal detachment);
      however, the ocular phenotype is not well defined. This report characterises eye
      findings of the syndrome in children with genetically confirmed disease. METHODS:
      Case series of Saudi children with previously documented homozygous mutations in
      COL18A1 or ADAMTS18. RESULTS: All eight children (4-15 years old; five families)
      had smooth (cryptless) irides, high myopia (-10 to -20 dioptres) and distinctive
      vitreo-retinal degeneration consisting of diffuse very severe retinal pigment
      epithelium atrophic changes with prominent choroidal vessel show, macular
      atrophic lesions with or without a 'punched out' appearance and white fibrillar
      vitreous condensations. In two probands and a sibling, this distinctive retinal
      appearance was the basis for initial clinical diagnosis. Six children had
      temporal ectopia lentis and four had posterior perinuclear lens opacity.
      Additional features included developmental delay (two), epilepsy (one) and
      heterotopic grey matter in the lateral ventricles (one). Four children had no
      clinically discernible occipital defect. CONCLUSION: Taken together, smooth
      iridies, ectopia lentis and characteristic vitreo-retinal degeneration seem
      pathognomonic. Although it is a defining feature of the syndrome, clinically
      discernible occipital defect is not a sine qua non for the diagnosis.
      Ophthalmologists are uniquely able to diagnose Knobloch syndrome.

PMID- 22399688
TI  - Glaucoma: a systemic condition?

PMID- 22399689
TI  - Cardiac autonomic dysfunction in patients with normal tension glaucoma: 24-h
      heart rate and blood pressure variability analysis.
AB  - AIMS: To define parameters of autonomic nervous system activity in patients with
      normal tension glaucoma (NTG). METHODS: Ambulatory 24-h ECG (Lifecard CF) and 24
      h blood pressure (BP) monitoring (SpaceLab 90207-30) were carried out in 54
      patients with NTG (44 women, mean age 59.7) and 43 matched control subjects (34
      women, mean age 57.0). Heart rate variability time and frequency domain
      parameters (low frequency (LF), high frequency (HF) and LF/HF ratio), BP
      variability (BPV), diurnal and nocturnal BP variables were compared between study
      groups. RESULTS: Patients with NTG demonstrated higher LF, LF/HF and lower HF
      values than control subjects for the 24-h, daytime and night-time periods. The
      mean 24-h, daytime and night-time LF/HF ratios were statistically higher in
      patients with glaucoma as compared to control subjects ((3.2+/-1.5 vs 2.2+/-0.8,
      p=0.0009), (3.5+/-1.7 vs 2.7+/-1.0, p=0.0173) and (2.6+/-1.7 vs 1.4+/-0.6,
      p=0.0001), respectively). There were no statistical differences in the mean BP
      during the whole day, daytime and night-time, and in BPV (10.4+/-1.9 vs 10.5+/
      2.1, p=0.790) between study groups. No difference was also found in the
      percentage decrease in night-time mean BP (12.3% vs 13.6%, p=0.720). 'Dippers',
      'non-dippers' and 'overdippers' with NTG showed significantly higher LF/HF ratio
      as compared to the same subgroups of control subjects. CONCLUSIONS: The
      sympathovagal balance of autonomic nervous system in patients with NTG shifted
      towards sympathetic activity however with no change of 24-h pattern of BPV as
      compared to controls.

PMID- 22399690
TI  - Cost-effectiveness of ranibizumab in treatment of diabetic macular oedema (DME)
      causing visual impairment: evidence from the RESTORE trial.
AB  - BACKGROUND/AIMS: To evaluate the cost-effectiveness of ranibizumab as either
      monotherapy or combined with laser therapy, compared with laser monotherapy, in
      the treatment of diabetic macular oedema (DME) causing visual impairment from a
      UK healthcare payer perspective. METHODS: A Markov model simulated long-term
      outcomes and costs of treating DME in one eye (BCVA <=75 letters) based on data
      from the RESTORE Phase III trial. Outcomes measured in quality-adjusted life
      years (QALYs) were simulated for a 15-year time horizon based on 12-month follow
      up from RESTORE and published long-term data. Costs included treatment, disease
      monitoring, visual impairment and blindness (at 2010 price levels). RESULTS:
      Ranibizumab monotherapy resulted in a 0.17 QALY gain at an incremental cost of
      L4191 relative to laser monotherapy, yielding an incremental cost-effectiveness
      ratio (ICER) of L24 028. Probabilistic sensitivity analysis showed a 64%
      probability of being cost-effective at a threshold of L30 000 per QALY. Combined
      ranibizumab and laser therapy resulted in a 0.13 QALY gain at an incremental cost
      of L4695 relative to laser monotherapy (ICER L36 106; 42% probability of ICER
      <L30 000). CONCLUSIONS: Based on RESTORE 1-year follow-up data, ranibizumab
      monotherapy appears to be cost-effective relative to laser monotherapy, the
      current standard of care. Cost-effectiveness of combination therapy is less
      certain. Ongoing studies will further inform on disease progression and the need
      for additional ranibizumab treatment.

PMID- 22399691
TI  - Corneal biomechanical properties and intraocular pressure measurement in patients
      with nanophthalmos.
AB  - AIMS: To compare the biomechanical properties of the cornea and intraocular
      pressure (IOP) between patients with nanophthalmos and age-matched controls.
      METHODS: In this prospective, cross-sectional and comparative study, 27 eyes of
      27 healthy individuals (control group) and 27 eyes of 27 patients with
      nanophthalmos (study group) were enrolled. Corneal hysteresis (CH), corneal
      resistance factor (CRF), corneal compensated intraocular pressure (IOPcc) and
      Goldmann correlated intraocular pressure (IOPg) were recorded for the right eye
      of each participant using Reichert Ocular Response Analyser measurements. Also,
      all participants in this study underwent a standardised ocular examination
      including IOP measurement with Goldmann applanation tonometry (IOP(GAT)), central
      corneal thickness and axial length (AL) assessments. RESULTS: Mean CH in the
      nanophthalmic eyes and in the control eyes were 13.3 +/- 2.4 mm Hg and 11.6 +/-
      1.7 mm Hg, respectively (p=0.003); mean CRF values in the nanophthalmic and the
      control eyes were 13.2 +/- 1.8 mm Hg and 11.4 +/- 1.9 mm Hg, respectively
      (p=0.001). Mean IOP(GAT) was 15.2 +/- 3.3 mm Hg in the nanophthalmic eyes and
      13.4 +/- 2.7 mm Hg in the control group (p=0.031); mean IOPg values for the
      nanophthalmic and the control groups were 17.1 +/- 5.3 mm Hg and 14.7 +/- 3.5 mm
      Hg, respectively (p=0.042). Mean IOPcc values in the nanophthalmic and the
      control group were 13.6 +/- 6.1 mm Hg and 14.8 +/- 3.2 mm Hg, respectively
      (p=0.365). CONCLUSION: The CH, CRF, IOPg and IOP(GAT) were significantly higher
      in the nanophthalmic eyes, whereas no significant differences in IOPcc were
      observed. These findings may be taken into account when measuring IOP values in
      patients with nanophthalmos.

PMID- 22399692
TI  - The clinical course of juvenile idiopathic arthritis-associated uveitis in
      childhood and puberty.
AB  - AIM: The long-term course of juvenile idiopathic arthritis (JIA)-associated
      uveitis is not known yet. This study investigates the course and activity of JIA
      associated uveitis in childhood and puberty. DESIGN: Retrospective study of the
      clinical data of 62 JIA patients with uveitis. The main outcome measurements
      consisted of uveitis activity measured as mean cell grade in the anterior
      chamber, topical and systemic medication and ocular complications related to
      disease activity. All data were scored and evaluated per year of age. RESULTS:
      Uveitis activity took a biphasic course with a quiet phase around the age of 9
      years and showed increased activity during early teenage years. The biphasic
      course was significantly related to age (p=0.048) but not to uveitis duration.
      More patients were treated with systemic immunosuppressive medication in
      estimated puberty years (63% in boys, 53% in girls) compared with prepuberty
      years (46% and 28%, respectively), although the difference was only significant
      in girls (p<0.001). The presence of cystoid macular oedema and papillitis was not
      significantly related to estimated puberty, but the development of an hypotonous
      eye was more frequently observed in boys in estimated puberty years (p=0.026).
      CONCLUSIONS: JIA-associated uveitis appears to take a biphasic course with the
      second phase of activity during early teenage years and more treatment with
      systemic immunosuppressive medication occurred during estimated puberty compared
      with prepuberty years.

PMID- 22399693
TI  - Spanish multicenter tafluprost tolerability study.
AB  - AIM: To evaluate the ocular surface symptoms and signs associated with
      preservative-free 0.0015% tafluprost in patients with glaucoma or ocular
      hypertension (OHT). METHODS: Prospective non-interventional, multicentre,
      observational study on 134 patients, naive or on previous treatment with another
      prostaglandin analogue. In each visit (V1 baseline visit, V2 at 1 month and V3 at
      3 months), patients evaluated five ocular surface symptoms as: absent, mild,
      moderate and severe. Parallelly, the ophthalmologist assessed the tear break-up
      time, keratitis, conjunctival hyperaemia, blepharitis, Schirmer test and tear
      meniscus. RESULTS: Patients with OHT (n=71, 53%) experienced a statistically
      significant improvement of all symptoms: stinging/burning/irritation, itching,
      foreign body sensation, tearing and dryness sensation at V3, while glaucoma
      patients improved all symptoms at both V2 and V3. In patients with OHT, all signs
      except Schirmer test improved and the decrease in hyperaemia was statistically
      significant. Eyes with glaucoma ameliorated the keratitis, hyperaemia and tear
      meniscus at V2 and V3 and the break-up time and blepharitis at V3. In the subset
      of patients with previous treatment (n=79, 58.9%), patients with OHT presented
      significant improvement of hyperaemia, yet the rest of signs did not decrease
      significantly or remained unchanged, while in patients with glaucoma all signs
      improved significantly at both visits. The intraocular pressure (IOP) drop in
      naive eyes was 22.2% (24.7-19.7 mm Hg) in OHT and 29.5% (33.7-25.3 mm Hg) in
      glaucoma eyes. In previously treated eyes, no statistically significant change in
      IOP was found. CONCLUSION: Preservative-free tafluprost is a well tolerated
      hypotensive agent that can be used in eyes with surface problems and in naive
      eyes.

PMID- 22399694
TI  - Correlates of age onset of type 2 diabetes among relatively young black and white
      adults in a community: the Bogalusa Heart Study.
AB  - OBJECTIVE: The risk factors for middle-age onset of type 2 diabetes are well
      known. However, information is scant regarding the age onset of type 2 diabetes
      and its correlates in community-based black and white relatively young adults.
      RESEARCH DESIGN AND METHODS: This prospective cohort study consisted of
      normoglycemic (n = 2,459) and type 2 diabetic (n = 144) adults aged 18-50 years
      who were followed for an average of 16 years. RESULTS: The incidence rate of the
      onset of type 2 diabetes was 1.6, 4.3, 3.9, and 3.4 per 1,000 person-years for
      age-groups 18-29, 30-39, and 40-50 and total sample, respectively. Incidences of
      diabetes increased with age by race and sex groups (P for trend <= 0.01); higher
      in black females versus white females and blacks versus whites in total sample (P
      < 0.05). In a multivariable Cox model, baseline parental diabetes (hazard ratio
      [HR] 5.24) and plasma insulin were significantly associated with diabetes
      incidence at the youngest age (18-29 years); black race, BMI, and glucose at age
      30-39 years; female sex, parental diabetes (HR 2.44), BMI, ratio of triglycerides
      and HDL cholesterol (TG/HDL-C ratio), and glucose at age 40-50 years; and black
      race, parental diabetes (HR 2.44), BMI, TG/HDL-C ratio, and glucose in whole
      cohort. Further, patients with diabetes, regardless of age onset, displayed a
      significantly higher prevalence of maternal history of diabetes at baseline (P <
      0.01). CONCLUSIONS: In relatively young adults, predictability of baseline
      cardiometabolic risk factors along with race, sex, and parental history of
      diabetes for the onset of type 2 diabetes varied by age-group. These findings
      have implications for early prevention and intervention in relatively young
      adults.

PMID- 22399695
TI  - Impact of insulin resistance on HCV treatment response and impact of HCV
      treatment on insulin sensitivity using direct measurements of insulin action.
AB  - OBJECTIVE: Insulin resistance, as measured by surrogate markers, is associated
      with lower response to hepatitis C virus (HCV) therapy and may improve with HCV
      eradication. We prospectively evaluated the impact of directly measured insulin
      resistance and abnormal glucose metabolism on achieving sustained virologic
      response (SVR) with HCV therapy and assessed whether SVR results in improved
      insulin sensitivity and fasting glucose. RESEARCH DESIGN AND METHODS: A total of
      50 noncirrhotic, nondiabetic, HCV-infected patients (27 untreated, 23 treated
      with pegylated interferon/ribavirin, nonrandomized) underwent clinical and
      histologic evaluation and 75-g oral glucose tolerance test. Insulin sensitivity
      was assessed directly with insulin suppression test by measuring steady-state
      plasma glucose (SSPG) concentration during a 240-min infusion of octreotide,
      glucose, and insulin. Of the subjects, 43 had at least one follow-up evaluation.
      RESULTS: Patient characteristics were median age 48, 57% male, and 52% white. SVR
      was achieved in 61% (14 of 23) of treated subjects. SVR was independently
      associated with HCV genotypes 2 and 3 (odds ratio 8.8 [95% CI 1.2-61.7]) but was
      not strongly associated with insulin sensitivity. When controlling for elapsed
      time between measurements, being on interferon, and BMI, SSPG decreased by 36
      mg/dL (-88 to 16) in those with SVR and decreased by 28 mg/dL (-93 to 38) in
      those without SVR, compared with the untreated group. BMI (coefficient 9.1 per 5
      units; 95% CI 5.3-12.9) and interferon use (coefficient 56; 95% CI 6.8-105) were
      associated with SSPG. CONCLUSIONS: Insulin resistance does not appear to be
      strongly associated with SVR. HCV therapy may improve insulin resistance
      regardless of virologic response; however, BMI and interferon use were clearly
      associated with insulin resistance.

PMID- 22399696
TI  - Independent associations of glucose status and arterial stiffness with left
      ventricular diastolic dysfunction: an 8-year follow-up of the Hoorn Study.
AB  - OBJECTIVE: To investigate relative contributions of glucose status and arterial
      stiffness to markers of left ventricular (LV) systolic and diastolic dysfunction
      after 8 years of follow-up. RESEARCH DESIGN AND METHODS: In the population-based
      prospective Hoorn Study, 394 individuals with preserved LV systolic and diastolic
      function participated, of whom 87 had impaired glucose metabolism and 128 had
      type 2 diabetes. Measurements including arterial ultrasound and echocardiography
      were performed according to standardized protocols. RESULTS: The presence of type
      2 diabetes was associated with more severe LV systolic and diastolic dysfunction
      8 years later: LV ejection fraction was 2.98% (95% CI 0.46-5.51) lower, and left
      atrial (LA) volume index, LV mass index, and tissue Doppler-derived E/e' were
      3.71 mL/m(2) (1.20-6.22), 5.86 g/m(2.7) (2.94-8.78), and 1.64 units (0.95-2.33)
      higher, respectively. Furthermore, presence of impaired glucose metabolism or
      type 2 diabetes was associated with 8-year increases in LV mass index. More
      arterial stiffness (measured as a lower distensibility) was associated with LV
      diastolic dysfunction 8 years later: LA volume index, LV mass index, and E/e' at
      follow-up were higher. Subsequent adjustments for baseline mean arterial pressure
      and/or LV diastolic dysfunction did not eliminate these associations.
      Associations of type 2 diabetes and arterial stiffness with markers of LV
      diastolic dysfunction were largely independent of each other. CONCLUSIONS: Both
      glucose status and arterial distensibility are independently associated with more
      severe LV diastolic dysfunction 8 years later and with deterioration of LV
      diastolic dysfunction. Therefore, type 2 diabetes and arterial stiffness may
      relate to LV diastolic dysfunction through different pathways.

PMID- 22399697
TI  - Vitamin D levels predict all-cause and cardiovascular disease mortality in
      subjects with the metabolic syndrome: the Ludwigshafen Risk and Cardiovascular
      Health (LURIC) Study.
AB  - OBJECTIVE: Optimal vitamin D levels are associated with reduced cardiovascular
      and all-cause mortality. We investigated whether optimal 25-hydroxyvitamin D
      (25[OH]D) is protective in individuals with the metabolic syndrome. RESEARCH
      DESIGN AND METHODS: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study
      is a cohort study of subjects referred for coronary angiography between 1997 and
      2000, from which 1,801 with the metabolic syndrome were investigated. Mortality
      was tracked for a median of 7.7 years. Multivariable survival analysis was used
      to estimate the association between 25(OH)D levels and mortality. RESULTS: Most
      subjects (92%) had suboptimal levels of 25(OH)D (<75 nmol/L), with 22.2% being
      severely deficient (<25 nmol/L). During follow-up, 462 deaths were recorded, 267
      (57.8%) of which were cardiovascular in origin. After full adjustment, including
      the metabolic syndrome components, those with optimal 25(OH)D levels showed a
      substantial reduction in all-cause (hazard ratio [HR] 0.25 [95% CI 0.13-0.46])
      and cardiovascular disease mortality (0.33 [0.16-0.66]) compared with those with
      severe vitamin D deficiency. For specific cardiovascular disease mortality, there
      was a strong reduction for sudden death (0.15 [0.04-0.63]) and congestive heart
      failure (0.24 [0.06-1.04]), but not for myocardial infarction. The reduction in
      mortality was dose-dependent for each of these causes. CONCLUSIONS: Optimal
      25(OH)D levels substantially lowered all-cause and cardiovascular disease
      mortality in subjects with the metabolic syndrome. These observations call for
      interventional studies that test whether vitamin D supplementation provides a
      useful adjunct in reducing mortality in these subjects.

PMID- 22399698
TI  - Cardiometabolic risk profiles and carotid atherosclerosis in individuals with
      prediabetes identified by fasting glucose, postchallenge glucose, and hemoglobin
      A1c criteria.
AB  - OBJECTIVE: We evaluated whether cardiometabolic risk profiles differ for subjects
      identified as having prediabetes by A1C, fasting glucose (FPG), or 2-h
      postchallenge glucose (2-PG) criteria. RESEARCH DESIGN AND METHODS:
      Atherosclerosis risk factors, oral glucose tolerance test, and ultrasound
      measurement of carotid intima-media thickness (IMT) were analyzed in 780
      nondiabetic individuals. RESULTS: Poor agreement existed for A1C and FPG criteria
      for identification of subjects with prediabetes (kappa coefficient = 0.332). No
      differences in cardiometabolic risk profiles were observed among the three groups
      of individuals with prediabetes by A1C only, FPG only, and both A1C and FPG. Poor
      agreement also existed for A1C and 2-PG criteria for identification of
      individuals with prediabetes (kappa coefficient = 0.299). No significant
      differences in cardiometabolic risk factors were observed between IGT-only and
      individuals with prediabetes by A1C and 2-PG. Compared with subjects with
      prediabetes identified by A1C only, IGT-only individuals exhibited a worse
      cardiometabolic risk profile, with significantly higher systolic blood pressure,
      pulse pressure, 2-h postchallenge insulin, triglycerides, high-sensitivity C
      reactive protein, and carotid IMT, and lower HDL cholesterol levels and insulin
      sensitivity. CONCLUSIONS: These results suggest that considerable discordance
      between A1C, FPG, and 2-PG exists for the identification of individuals with
      prediabetes and that the cardiometabolic risk profile of these individuals varies
      by metabolic parameter, with 2-PG showing the stronger association with
      cardiometabolic risk factors and subclinical atherosclerosis than FPG or A1C.

PMID- 22399700
TI  - Exercise therapy in type 2 diabetes: is daily exercise required to optimize
      glycemic control?
AB  - OBJECTIVE: Given the transient nature of exercise-induced improvements in insulin
      sensitivity, it has been speculated that daily exercise is preferred to maximize
      the benefits of exercise for glycemic control. The current study investigates the
      impact of daily exercise versus exercise performed every other day on glycemic
      control in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Thirty type 2
      diabetic patients (age 60 +/- 1 years, BMI 30.4 +/- 0.7 kg/m(2), and HbA(1c) 7.2
      +/- 0.2%) participated in a randomized crossover experiment. Subjects were
      studied on three occasions for 3 days under strict dietary standardization but
      otherwise free-living conditions. Blood glucose homeostasis was assessed by
      continuous glucose monitoring over 48 h during which subjects performed no
      exercise (control) or 60 min of cycling exercise (50% maximal workload capacity)
      distributed either as a single session performed every other day or as 30 min of
      exercise performed daily. RESULTS: The prevalence of hyperglycemia (blood glucose
      >10 mmol/L) was reduced from 7:40 +/- 1:00 h:min per day (32 +/- 4% of the time)
      to 5:46 +/- 0:58 and 5:51 +/- 0:47 h:min per day, representing 24 +/- 4 and 24 +/
      3% of the time, when exercise was performed either daily or every other day,
      respectively (P < 0.001 for both treatments). No differences were observed
      between the impact of daily exercise and exercise performed every other day.
      CONCLUSIONS: A short 30-min session of moderate-intensity endurance-type exercise
      substantially reduces the prevalence of hyperglycemia throughout the subsequent
      day in type 2 diabetic patients. When total work is being matched, daily exercise
      does not further improve daily glycemia compared with exercise performed every
      other day.

PMID- 22399699
TI  - Changes in physical fitness predict improvements in modifiable cardiovascular
      risk factors independently of body weight loss in subjects with type 2 diabetes
      participating in the Italian Diabetes and Exercise Study (IDES).
AB  - OBJECTIVE: Physical fitness is inversely related to mortality in the general
      population and in subjects with type 2 diabetes. Here, we present data concerning
      the relationship between changes in physical fitness and modifiable
      cardiovascular risk factors in subjects with type 2 diabetes from the Italian
      Diabetes and Exercise Study. RESEARCH DESIGN AND METHODS: Sedentary patients with
      type 2 diabetes (n = 606) were enrolled in 22 outpatient diabetes clinics and
      randomized to twice-a-week supervised aerobic and resistance training plus
      exercise counseling versus counseling alone for 12 months. Baseline to end-of
      study changes in cardiorespiratory fitness, strength, and flexibility, as
      assessed by Vo(2max) estimation, a 5-8 maximal repetition test, and a hip/trunk
      flexibility test, respectively, were calculated in the whole cohort, and multiple
      regression analyses were applied to assess the relationship with cardiovascular
      risk factors. RESULTS: Changes in Vo(2max), upper and lower body strength, and
      flexibility were significantly associated with the variation in the volume of
      physical activity, HbA(1c), BMI, waist circumference, high-sensitivity C-reactive
      protein (hs-CRP), coronary heart disease (CHD) risk score, and inversely, HDL
      cholesterol. Changes in fitness predicted improvements in HbA(1c), waist
      circumference, HDL cholesterol, hs-CRP, and CHD risk score, independent of study
      arm, BMI, and in case of strength, also waist circumference. CONCLUSIONS:
      Physical activity/exercise-induced increases in fitness, particularly muscular,
      predict improvements in cardiovascular risk factors in subjects with type 2
      diabetes independently of weight loss, thus indicating the need for targeting
      fitness in these individuals, particularly in subjects who struggle to lose
      weight.

PMID- 22399702
TI  - Is there a role for acute hospitals in tackling public health?

PMID- 22399701
TI  - BMI-mortality paradox and fitness in African American and Caucasian men with type
      2 diabetes.
AB  - OBJECTIVE: To assess the association between BMI, fitness, and mortality in
      African American and Caucasian men with type 2 diabetes and to explore racial
      differences in this association. RESEARCH DESIGN AND METHODS: We used prospective
      observational data from Veterans Affairs Medical Centers in Washington, DC, and
      Palo Alto, California. Our cohort (N = 4,156; mean age 60 +/- 10.3 years)
      consisted of 2,013 African Americans (mean age, 59.5 +/- 9.9 years), 2,000
      Caucasians (mean age, 60.8 +/- 10.5 years), and 143 of unknown race/ethnicity.
      BMI, cardiac risk factors, medications, and peak exercise capacity in metabolic
      equivalents (METs) were assessed during 1986 and 2010. All-cause mortality was
      assessed across BMI and fitness categories. RESULTS: There were 1,074 deaths
      during a median follow-up period of 7.5 years. A paradoxic BMI-mortality
      association was observed, with significantly higher risk among those with a BMI
      between 18.5 and 24.9 kg/m(2) (hazard ratio [HR] 1.70 [95% CI 1.36-2.1]) compared
      with the obese category (BMI >= 35 kg/m(2)). This association was accentuated in
      African Americans (HR 1.95 [95% CI 1.44-2.63]) versus Caucasians (HR 1.53 [1.0
      2.1]). The fitness-mortality risk association for the entire cohort and within
      BMI categories was inverse, independent, and graded. Mortality risks were 12%
      lower for each 1-MET increase in exercise capacity, and ~35-55% lower for those
      with an exercise capacity >5 METs compared with the least fit (<= 5 METs).
      CONCLUSIONS A paradoxic BMI-mortality risk association was observed in African
      American and Caucasian patients with diabetes. The exercise capacity-mortality
      risk association was inverse, independent, and graded in all BMI categories but
      was more potent in those with a BMI >= 25 kg/m(2).

PMID- 22399703
TI  - How to judge the value of innovation.

PMID- 22399704
TI  - Incidence rates.

PMID- 22399705
TI  - Who's afraid of whom?

PMID- 22399707
TI  - The medium and the message.

PMID- 22399708
TI  - After the bill, what next?

PMID- 22399709
TI  - Medicine's Leveson.

PMID- 22399710
TI  - NHS staff gear up for climate week with energy efficient pledges.

PMID- 22399711
TI  - Syria: tales of life, death, and dignity.

PMID- 22399714
TI  - A man with bloody diarrhoea.

PMID- 22399715
TI  - Overexpression of heat shock protein 70 and its relationship to intestine under
      acute heat stress in broilers: 1. Intestinal structure and digestive function.
AB  - The objective of this study was to investigate the relationship between heat
      shock protein 70 (HSP70) overexpression and intestinal structure and digestive
      function in heat-stressed broilers. In total, 240 male broilers were injected
      intraperitoneally with l-(1)-glutamine (0.75 mg/kg of BW) or quercetin (5 mg/kg
      of BW). Twenty-four hours later, they were heat-stressed for 0, 2, 3, 5, and 10
      h, respectively, under 36 +/- 1 degrees C. The HSP70 protein and mRNA expression
      were obviously elevated at 3 h of heat stress, and glutamine induced the
      overexpression of HSP70 in the jejunal mucosa at different heat-stress times (P <
      0.01). No significant change of jejunal villus height, crypt, and villus
      height:crypt ratio were observed after heat stress, and there were no effects of
      HSP70 overexpression on intestinal morphology under heat stress. The
      overexpression of HSP70 significantly increased alkaline phosphatase activity at
      3 h of heat stress (P < 0.01). There was a strong correlation between HSP70
      expression and the digestive enzyme activity (P <= 0.001). The overexpression of
      HSP70 significantly increased the amylase, lipase, and trypsin activity under
      heat stress (P < 0.001). These results demonstrated that glutamine was a good
      HSP70 enhancer to establish an HSP70 overexpression model. Although the
      overexpression of HSP70 did not change intestinal morphology conditions, it
      significantly increased broiler digestive enzyme activity under heat stress.

PMID- 22399716
TI  - Overexpression of heat shock protein 70 and its relationship to intestine under
      acute heat stress in broilers: 2. Intestinal oxidative stress.
AB  - Oxidative stress injury is one important factor in intestinal mucosal barrier
      damage. Expression of heat shock protein (HSP)70 is an endogenous mechanism by
      which living cells adapt to stress. This study was undertaken to investigate the
      protective effects of HSP70 on intestinal oxidative stress. Two hundred and forty
      broilers were injected intraperitoneally with HSP70 inducer l-(1)-glutamine or
      with the inhibitor quercetin. Twenty-four hours later, they were heat stressed
      for 0, 2, 3, 5, and 10 h, respectively, at 36 +/- 1 degrees C. The l-(1)
      glutamine significantly increased HSP70 expression (P < 0.001). At 2 h or 3 h of
      heat stress, the HSP70 expression obviously elevated (P < 0.001). Levels of
      corticosterone and the heterophil:lymphocyte ratio significantly increased when
      HSP70 expression was inhibited (P < 0.0001). Serum corticosterone was negatively
      correlated with the HSP70 expression at 3 h of heat stress (P = 0.0015; R = 
      0.6537). Heat shock protein 70 significantly protected the integrity of the
      intestinal mucosa from heat stress, with significantly decreased lactic
      dehydrogenase when HSP70 expression was enhanced (P < 0.001). In addition, heat
      stress time significantly affected the lactic dehydrogenase release (P < 0.001).
      Furthermore, HSP70 significantly elevated antioxidant enzyme activities (such as
      superoxide dismutase, glutathione peroxidase, and total antioxidant capacity) and
      inhibited lipid peroxidation to relieve intestinal mucosal oxidative injury (P <
      0.001). These results suggest that HSP70 is capable of protecting the intestinal
      mucosa from heat-stress injury by improving antioxidant capacity of broilers and
      inhibiting the lipid peroxidation production.

PMID- 22399717
TI  - Ameliorative effect of a microbial feed additive on infectious bronchitis virus
      antibody titer and stress index in broiler chicks fed deoxynivalenol.
AB  - Although acute mycotoxicoses are rare in poultry production, chronic exposure to
      low levels of mycotoxins is responsible for reduced productivity and increased
      susceptibility to infectious diseases. Deoxynivalenol (DON) is known to modulate
      immune function, but only a few studies have investigated the effect of DON on
      the vaccinal immune response. In addition, the effects of Mycofix select (Biomin
      GmbH, Herzogenburg, Austria) supplementation to DON-contaminated broiler diets
      have not yet been demonstrated. Therefore, an experiment with 1-d-old male
      broilers (Ross 308) was carried out to examine the effects of feeding DON
      contaminated low-protein grower diets on performance, serum biochemical
      parameters, lymphoid organ weight, and antibody titers to infectious bronchitis
      vaccination in serum and to evaluate the effects of Mycofix select dietary
      supplementation in either the presence or absence of DON in broilers. In total,
      thirty-two 1-d-old broiler chicks were randomly assigned to 1 of the 4 dietary
      treatments for 5 wk. The dietary treatments were 1) control; 2) artificially
      contaminated diets with 10 mg of DON/kg of diet; 3) DON-contaminated diets
      supplemented with Mycofix select; and 4) control diet supplemented with Mycofix
      select. Feeding of contaminated diets decreased (P = 0.000) the feed intake, BW
      (P = 0.001), BW gain (P = 0.044), and feed efficiency during the grower phase.
      Deoxynivalenol affected the blood biochemistry, whereas plasma total protein and
      uric acid concentrations in birds fed contaminated grains were decreased compared
      with those of the controls. Moreover, in birds fed contaminated feeds, there was
      a tendency to reduce triglycerides in the plasma (P = 0.090), suggesting that DON
      in the diets affected protein and lipid metabolism in broiler chickens. The
      feeding of contaminated diets altered the immune response in broilers by reducing
      the total lymphocyte count. Similarly, the antibody response against infectious
      bronchitis vaccination antigens was decreased (P = 0.003) after feeding
      contaminated diets, compared with the controls. Moreover, contamination of the
      broiler diet with DON increased the heteropil:lymphocyte ratio (stress index),
      suggesting that DON elevated the physiological stress responses of broilers.
      However, feeding of DON-containing diets did not alter the other plasma
      constituents, including activities of enzymes. Mycofix select addition to the DON
      contaminated feed led to normal immunological and physiological functions in
      broilers that were comparable with those of the control group, indicating that
      the addition of the additive to the DON-contaminated feed of the broilers
      effectively alleviated the alterations caused by DON. It was concluded that
      broiler performance and some blood and immunological parameters were adversely
      affected by feeding diets contaminated with the Fusarium mycotoxin DON. However,
      the dietary Mycofix select supplementation as a detoxifying agent was successful
      in overcoming the mycotoxin-related effects.

PMID- 22399718
TI  - Cage hygiene, laying location, and egg quality: the effects of linings and litter
      provision in furnished cages for laying hens.
AB  - This study investigates the influence of litter provision and linings used for
      nests and pecking and scratching areas on cage hygiene, laying location, and egg
      quality. Research was carried out in furnished cages, each housing 60 beak
      trimmed ISA Brown hens. Four different treatments were compared in a factorial
      arrangement, including 2 different nest linings (artificial turf vs. plastic
      mesh), either used alone or combined with the use of litter (wheat bran) spread
      over the rubber mat in the pecking and scratching area (PSA). An additional
      treatment, using artificial turf mat in the PSA and nests (as commonly used in
      commercial flocks), was used to compare the effect of PSA lining in the other
      treatments. We observed laying location, the number of dirty and broken eggs, the
      microbiological contamination of eggshells according to laying location, and
      general cage hygiene. The use of nests for laying decreased when they were lined
      with plastic mesh. Eggs laid outside the nest were of lower quality than those
      laid inside it, and this was particularly true for eggs laid in the PSA. Although
      hygiene was low on artificial turf mats, eggs laid on PSA covered with a rubber
      mat were dirtier and had a higher count of mesophilic bacteria on the eggshell
      than those laid on PSA covered with an artificial turf mat. Rubber mats in PSA
      were rapidly destroyed and proved to be unsuitable. The provision of litter had
      no effect on cage hygiene but substantially increased wear on mats. This study
      shows nest lining and litter provision methods to be key factors that need to be
      taken into account to encourage the use of nest boxes for laying, and hence, to
      ensure good egg quality. Further research into new linings for PSA is needed for
      the future improvement of egg-laying conditions.

PMID- 22399719
TI  - Effects of selective serotonin antagonism on central neurotransmission.
AB  - Aggression and cannibalism in laying hens can differ in intensity and degree due
      to many factors, including genetics. Previous behavioral analysis of 2 strains of
      White Leghorns, DeKalb XL (DXL) and HGPS (a group-selected line for high group
      productivity and survivability), revealed high and low aggressive phenotypes,
      respectively. However, the exact genetic mechanisms mediating aggressiveness are
      currently unknown. Analysis of serotonin (5-HT) mediation of aggression in
      subordinate hens of these strains revealed increases in aggression in DXL hens
      following antagonism of the 5-HT1A receptor and in HGPS hens following antagonism
      of the 5-HT1B receptor. Here, we investigate the different neurotransmitter
      response in the hypothalamus and raphe nucleus mediating these aggressive
      responses to receptor antagonism. Elevated aggressive response to 5-HT1B
      antagonism by HGPS hens was also accompanied by a decrease in raphe nucleus
      dopamine (DA) and an increase in DA turnover. Increased aggressiveness in DXL
      hens did not coincide with a reduction in raphe nucleus 5-HT or turnover (as
      indicated by 5-hydroxyindoleacetic acid levels) following 5-HT1A antagonism. A
      reduction in 5-hydroxyindoleacetic acid (but not 5-HT) was seen in HGPS hens
      treated with 5-HT1A antagonist; however, these hens exhibited no change in
      aggressive behaviors. Our data show evidence of different heritable mechanisms of
      neurotransmitter regulation of aggressive response, specifically heritable
      differences in the interaction between 5-HT and catecholamines in regulating
      aggression.

PMID- 22399720
TI  - The effects of genotype on embryonic development in eggs from divergent turkey
      genotypes.
AB  - Unique turkey genotypes and reciprocal crosses of these lines were used to study
      the relationship between egg size, posthatch growth potential, and selected
      aspects of embryonic development. A line of turkeys selected for increased egg
      production (E), its randombred control line (RBC1), a line selected for increased
      16-wk BW (F line), and its randombred control line (RBC2) were the pure lines
      used in each of 2 experiments. In experiment 1, a sample of E-line hens were
      mated to either E line (E/E) or RBC1 toms (RBC1/E), and RBC1 hens were mated to
      RBC1 toms (RBC1/RBC1). Egg weight at set and at 25 d of incubation was
      significantly lower in the E/E and RBC1/E crosses compared with that of the
      RBC1/RBC1 eggs. On d 21 and 25 of incubation and at hatch, the yolk-free wet
      embryo weights of E/E and RBC1/E embryos were similar, and both weighed
      significantly less than the RBC1/RBC1 embryos (P <= 0.001). Similar observations
      were observed for the residual yolk sac weight at each of those developmental
      ages. In experiment 2, embryos from the F line, RBC2, RBC1, E, and 2 reciprocal
      crosses (RBC1/E, E/RBC1) were compared at various time points during the course
      of incubation. Egg weight was consistently highest in the F line and lowest in
      the E line and intermediate in the RBC1 and RBC2 lines. Egg weight followed the
      maternal genotype in the E/RBC1 and RBC1/E reciprocal crosses. On embryonic d 19,
      23, and 26, the order of yolk-free weight embryo weights followed closely the
      pattern observed for egg weight. In summary, egg weight and embryonic development
      is largely controlled by the maternal genotype. This should be considered when
      making inference to posthatch selection effects on embryonic development.

PMID- 22399721
TI  - Telomeric DNA quantity, DNA damage, and heat shock protein gene expression as
      physiological stress markers in chickens.
AB  - In this longitudinal study with Single Comb White Leghorn chickens, we
      investigated the effects of stress conditions in birds that were subjected to a
      high stocking density with feed restrictions on the quantity of telomeric DNA,
      the rate of DNA damage, and the expression levels of heat shock proteins (HSP)
      and hydroxyl-3-methyl-glutaryl coenzyme A reductase (HMGCR) genes. The telomere
      length and telomere-shortening rates were analyzed by quantitative fluorescence
      in situ hybridization on the nuclei of lymphocytes. The DNA damage rate of
      lymphocytes was quantified by the comet assay. The expression levels of HSP70,
      HSP90, and HMGCR genes were measured by quantitative real-time PCR in
      lymphocytes. The telomere-shortening rate of the lymphocytes was significantly
      higher in the stress group than in the control. The DNA damage also increased in
      birds raised under stress conditions, as compared with the control group. The
      stress conditions had a significant effect on the expressions of HMGCR and
      HSP90alpha in lymphocytes but had no significance on HSP70 and HSP90beta in
      blood. We conclude that the telomere length, especially the telomere-shortening
      rates, the quantification of total DNA damage, and the expression levels of the
      HMGCR and HSP90alpha genes can be used as sensitive physiological stress markers
      in chickens.

PMID- 22399722
TI  - Efficacy of protected sodium butyrate, a protected blend of essential oils, their
      combination, and Bacillus amyloliquefaciens spore suspension against artificially
      induced necrotic enteritis in broilers.
AB  - Necrotic enteritis caused by Clostridium perfringens leads to serious economical
      losses to the poultry industry. There is a growing need to find effective,
      nontoxic, antibiotic alternatives to prevent and cure the disease. In our study,
      the efficacy of protected sodium butyrate at 1.5 g/kg (BP70), a Bacillus
      amyloliquefaciens spore suspension with 10(9) cfu/g (BAL; Ecobiol), a protected
      blend of essential oils (1%) at 1.5 g/kg (EO), and a combination of sodium
      butyrate with essential oils (1%) protected with vegetable fat at 1.5 g/kg
      (BP70+EO; Natesse) was investigated in an artifical C. perfringens-infection
      model. Body weight gain, gross pathological and histopathological lesion scores,
      villus lengths, and villus length:crypt depth ratio was determined and compared
      with the control group. Broilers infected with C. perfringens and treated with
      essential oils or the combination of sodium butyrate and essential oils showed
      significantly better BW gain (P < 0.05), increased villus length and villus
      length:crypt depth ratio (P < 0.001), and decreased gross pathological and
      histopathological lesion scores (P < 0.05) compared with the control. Sodium
      butyrate alone and B. amyloliquefaciens spore suspension had no beneficial
      effects on the course of the disease in this study. According to our results, the
      protected combination of sodium butyrate and essential oils, as well as the
      protected essential oils, can be potential candidates for the prevention and
      treatment of necrotic enteritis in broiler chickens.

PMID- 22399723
TI  - Deoxynivalenol as a contaminant of broiler feed: effects on bird performance and
      response to common vaccines.
AB  - Recent data suggest that Fusarium trichothecenes may reduce broiler performance
      at levels previously thought not to affect this variable in chickens. In the
      present study, we investigated the effects of deoxynivalenol (DON), a type-B
      trichothecene, on broilers. Male broilers at 7 d of age were fed either a basal
      diet (0.265 +/- 0.048 mg of DON; 0.013 +/- 0.001 mg of zearalenone/kg), a low DON
      diet (1.68 mg of DON/kg; 0.145 +/- 0.007 mg of zearalenone/kg), or a high DON
      diet (12.209 +/- 1.149 mg of DON/kg; 1.094 +/- 0.244 mg of zearalenone/kg).
      Increasing levels of DON decreased the weekly weight gain linearly (P <= 0.041)
      during the first 3 wk of exposure; there were no significant differences in the
      weight gain of the birds after wk 3. With increasing levels of DON, the titers
      against Newcastle disease virus increased linearly during wk 2 (P = 0.022) and wk
      4 (P = 0.033) of exposure, whereas the titers against infectious bronchitis virus
      decreased linearly (P = 0.006) during wk 5 of exposure. The serum protein
      concentration increased linearly (P = 0.017) during wk 2 and quadratically (P =
      0.002) during wk 4 of exposure. Under these experimental conditions, the
      performance and vaccine response of the broilers were modulated to varying
      degrees at concentrations of DON that are currently permitted (up to 5 mg/kg of
      diet) in many countries. Further studies are therefore required to clarify the
      implications of these results on the welfare of chickens.

PMID- 22399724
TI  - Deoxynivalenol as a contaminant of broiler feed: intestinal development,
      absorptive functionality, and metabolism of the mycotoxin.
AB  - Deoxynivalenol (DON) has been recently documented to deteriorate intestinal
      morphology in chickens at dietary doses that are regarded as safe for this
      species. The present trial was conducted to explore the significance of these
      morphological changes in relation to intestinal absorptive functionality and DON
      metabolism. Ross broilers at 7 d of age were fed either a basal diet (0.265 +/-
      0.048 mg of DON/kg; 0.013 +/- 0.001 mg of zearalenone/kg), a low DON diet (1.68
      mg of DON/kg; 0.145 +/- 0.007 mg of zearalenone/kg), or a high DON diet (12.209
      +/- 1.149 mg of DON/kg; 1.094 +/- 0.244 mg of zearalenone/kg). The DON diets (to
      variable degrees) progressively decreased the relative density (weight:length) of
      the small intestine with increasing exposure length, which could be correlated
      with a decrease in villus height in the small intestine. Short circuit current of
      the jejunal epithelium, reflecting transport function of the epithelium per unit
      area, was reduced (P = 0.001) in the birds fed the high DON diet. The increasing
      dietary level of DON linearly (P = 0.035) increased the length of the jejunum in
      wk 4 of exposure, resulting in conservation of macronutrient retention. Upon
      challenging the birds with a fixed amount of DON after wk 5 of exposure, higher
      (P <= 0.033) amounts of DON and the detoxification metabolite (de-epoxy-DON) were
      found at 5 h postchallenge in the guts of birds raised on the DON diets. The
      increasing level of previous exposure to DON linearly (P = 0.040) decreased the
      plasma level of DON in the birds at 1 h postchallenge. The amounts of zearalenone
      and its analogs in the gut and plasma also followed a trend similar to that for
      DON. These data suggest that intestines in chickens may adapt to a chronic DON
      challenge by morphological and functional modifications. The birds having
      previous exposure to Fusarium mycotoxins showed moderate detoxification coupled
      with reduced transfer of the mycotoxins to systemic circulation. Some metabolites
      of zearalenone found in this study were previously unknown for chickens.

PMID- 22399725
TI  - Seroprevalence of Newcastle disease and other infectious diseases in backyard
      chickens at markets in Eastern Shewa zone, Ethiopia.
AB  - This study was conducted to estimate the seroprevalence of Newcastle disease
      (ND), Pasteurella multocida (PM) infection, Mycoplasma gallisepticum (MG)
      infection, and infectious bursal disease (IBD) and to assess the level of
      concurrent seropositivity during the dry and wet seasons of the year 2010. In
      total, 234 and 216 sera were collected during the dry and wet seasons,
      respectively, from unvaccinated backyard chickens at 4 live poultry markets in 2
      woredas (districts) of Eastern Shewa zone, Ethiopia, and were tested using
      commercial ELISA kits. The overall seroprevalence of ND, PM, MG, and IBD was 5.9,
      66.2, 57.7, and 91.9%, respectively, during the dry season, and 6.0, 63.4, 78.7,
      and 96.3%, respectively, during the wet season. The seroprevalence of MG was
      higher (P < 0.001) during the wet season than during the dry season and higher (P
      = 0.002) in Adami-Tulu-Jido-Kombolcha woreda (74%) than in Ada'a woreda (60%).
      Area and season had no significant effect on the seroprevalence of ND, IBD, and
      PM, indicating the widespread presence of those pathogens throughout the year in
      the study area. Of all the chickens tested, 85.6% had antibodies concurrently to
      more than one of the pathogens investigated. Birds were concurrently seropositive
      to more diseases during the wet season (median = 3) than during the dry season
      (median = 2; P = 0.002). As serology is not able to distinguish between strains,
      further studies are warranted to better understand the circulating strains, their
      interactions, and their economic effect on backyard poultry production in
      Ethiopia.

PMID- 22399726
TI  - A wire-flooring model for inducing lameness in broilers: evaluation of probiotics
      as a prophylactic treatment.
AB  - Bacterial chondronecrosis with osteomyelitis (BCO) is the most common cause of
      lameness in commercial broilers. Bacteria entering the blood via translocation
      from the respiratory system or gastrointestinal tract spread hematogenously to
      the proximal epiphyseal-physeal cartilage of rapidly growing femora and tibiae,
      causing BCO. We tested the hypothesis that rearing broilers on wire flooring
      should increase the incidence of BCO by persistently imposing additional torque
      and shear stress on susceptible leg joints. We also tested the hypothesis that
      probiotics might attenuate bacterial translocation and thereby reduce the
      incidence of BCO. In 5 independent experiments using 4 commercial lines, broilers
      grown on wire flooring developed lameness attributable predominately to BCO. The
      fastest-growing birds were not necessarily the most susceptible to lameness on
      wire flooring, nor did the genders differ in susceptibility in the 2 experiments
      that included both male and female broilers. The pathogenesis of BCO is not
      instantaneous, and accordingly, many broilers that did not exhibit lameness,
      nevertheless, did possess early pathognomonic lesions. These subclinical lesions
      were equally likely to develop in the right or left leg. The lesion status of the
      proximal femoral head did not determine the lesion status of the ipsilateral or
      contralateral proximal tibial head and vice versa. Broilers reared on wire
      flooring consistently had higher incidences of lameness than hatch-mates reared
      on wood-shavings litter. Adding probiotics to the diet beginning at 1 d of age
      consistently reduced the incidence of lameness for broilers reared on wire
      flooring. These experiments indicate that probiotics administered
      prophylactically may constitute an alternative to antibiotics for reducing
      lameness attributable to BCO. Rearing broilers on wire flooring provides an
      important new research model for investigating the etiology, pathogenesis, and
      treatment strategies for BCO.

PMID- 22399727
TI  - Survey on sulfonamide antibiotic-resistant genotype and phenotype of avian
      Escherichia coli in North China.
AB  - It is important for the prevention and treatment of colibacillosis to monitor
      drug resistance in Escherichia coli. To choose effective drugs to prevent and
      control avian colibacillosis in North China, we investigated the resistance of
      164 E. coli isolates (from Beijing, Tianjin, Inner Mongolia, Shanxi, and Hebei
      regions of China) to commonly used clinical sulfonamide antibiotics using a drug
      susceptibility test. The results show that the rates of resistance to
      sulfamonomethoxine and sulfamethoxazole-trimethoprim were 90.24% (148/164) and
      73.17% (120/164), respectively. To explore the reasons for wide drug resistance,
      sulfonamide resistance genes were detected by PCR. Of the isolates, 90.85%
      (149/164) carried sulfonamide resistance genes. Therefore, resistance of avian E.
      coli to sulfonamide antibiotics is very serious in North China, perhaps because
      of the existence of resistance genes, but other resistance mechanisms may also
      contribute to tolerogenesis.

PMID- 22399728
TI  - Effect of metabolic efficiency and intestinal morphology on variability in n-3
      polyunsaturated fatty acid enrichment of eggs.
AB  - The effect of metabolic efficiency and associated gut characteristics of laying
      hens on the variability of transfer of dietary n-3 polyunsaturated fatty acids
      (PUFA) to the egg was examined in laying hens at 56 wk of age. An empirical
      energetics model was used to categorize individual hens into energetically
      efficient or nonefficient treatments based on residual maintenance ME
      requirement. Birds were then provided a diet containing an extruded flax product
      as a source of n-3 PUFA for 14 d. Egg traits were determined and yolks collected
      at 0 d and 14 d for measurement of fatty acid composition and variation in fatty
      acid levels within hen efficiency class. Gut length and duodenal
      histomorphometric indices were assessed after the 14-d experimental period.
      Efficient hens had a 96.01% rate of lay compared with 88.63% in nonefficient
      hens. After 14 d of feeding, the concentration of n-3 PUFA increased (151.6 vs.
      315.8 mg/egg) in the egg yolk whereas n-6 PUFA, saturated fatty acids, and
      monounsaturated fatty acids were reduced (P < 0.001). Energetic efficiency had no
      additional effect on these measurements. However, egg yolks from efficient birds
      had less alpha-linolenic acid but more docosapentaenoic acid than nonefficient
      birds, suggesting a greater up-conversion of medium-chain (alpha-linolenic acid)
      to long-chain fatty acids (docosapentaenoic acid) in efficient birds. After 14 d,
      the CV for total n-3 PUFA in egg yolks from efficient hens was lower than that
      from nonefficient birds (11.1 vs. 21.4), indicating a more uniform level of
      enrichment. Furthermore, efficient hens had longer duodenal villi (P = 0.02),
      resulting in a greater absorptive villi surface area (0.13 mm(2)/villi) than in
      nonefficient birds (0.10 mm(2)/villi; P = 0.01). Increased uniformity of n-3 PUFA
      enrichment of table eggs could be possible through focus on metabolic efficiency
      and gut absorptive condition in laying hens.

PMID- 22399729
TI  - Ileal endogenous amino acid losses: response of broiler chickens to fiber and
      mild coccidial vaccine challenge.
AB  - The effects of mild coccidial vaccine (5* dose) challenge and fiber levels on
      ileal endogenous amino acid (EAA) losses was determined in 26-d-old broiler
      chickens using the regression method. Birds were fed semipurified diets
      containing 3 levels of casein (40, 80, or 120 g/kg of diet) as the only source of
      dietary protein at 2 levels of fiber (purified cellulose at 25 or 75 g/kg of
      diet). One half of the experimental birds were gavaged with coccidial vaccine on
      d 20. The 3 levels of casein were used to determine EAA losses for each replicate
      cage of birds. The design of the study was a randomized complete block employing
      a factorial arrangement of treatments with 2 levels of coccidial challenge
      (control or unchallenged, and challenged) and 2 levels of fiber, with 6 replicate
      cages per treatment and 8 birds per cage. Birds were killed on d 26 and contents
      from the entire ileum were flushed with distilled water and stored at -20 degrees
      C until processed. Ileal EAA losses were determined from the ordinate intercept,
      at zero amino acid (AA) intake, of the regression of ileal digesta AA
      concentration in milligrams per kilogram of DM intake against dietary AA intake
      in milligrams per kilogram of DM. The effect of fiber level on EAA losses,
      expressed in milligrams per kilogram of DM intake, were higher (P < 0.05) for
      most of the AA in birds fed 25 g of fiber/kg of diet. Coccidial vaccine challenge
      decreased (P < 0.05) EAA losses for 8 of the 18 AA. A significant interaction
      between fiber level and coccidial vaccine challenge was obtained for all AA
      except His and Lys. Coccidial vaccine challenge resulted in increased (P < 0.05)
      NaPi-IIb expression. The results suggest that ileal EAA loss is higher in
      challenged birds fed the diet containing 25 g of fiber/kg of diet. Changes in EAA
      losses as a result of dietary fiber level and coccidial infection are important
      in amino acid nutrition of the broiler chicken.

PMID- 22399730
TI  - Interactive effects of age, sex, and strain on apparent ileal amino acid
      digestibility of soybean meal and an animal by-product blend in broilers.
AB  - The objectives of this study were to determine if age, sex, and strain of
      broilers affect the apparent ileal amino acid digestibility (AID) of soybean meal
      and an animal by-product blend. Chicks from 2 broiler strains, 1 commercially
      available and the other in the test phase, were obtained from a common hatchery,
      feather-sexed, and placed into floor pens. The birds received common diets while
      on floor pens. Birds were transferred to metabolism crates for 2 ileal
      digestibility trials conducted at 3 and 6 wk of age. Two semipurified diets were
      formulated with each of the feed ingredients providing all of the amino acids
      (AA) in the diets. Diets were formulated to contain 20% CP, with chromic oxide
      added to the diet at 0.30% as the indigestible marker. The experimental diets
      were fed for a 72-h period after an overnight fast to 8 replicate cages of 5
      birds per cage. Upon completion of the experimental periods (i.e., d 22 and 43),
      birds were euthanized and ileal digesta samples were collected and pooled by pen,
      frozen, lyophilized, and analyzed for AA and chromium concentrations. For soybean
      meal, no main effects were observed for age, sex, or strain; however, significant
      (P <= 0.05) 3-way interactions were observed for several dispensable and
      indispensable AA. Statistical analyses of these interactions indicate the AID of
      soybean meal may be different for 42-d males of the test strain. For the animal
      by-product blend, only main effects were significant for each AA, with the
      exception of Ile and Tyr. Main effect of strain was observed for most of the AA,
      showing that the commercially available strain had higher AID than the test
      strain. Also, significant main effect of age indicated that the AID for animal by
      product blend was higher at 42 d than at 21 d. Evaluation of these 2 ingredients
      showed that age, sex, and strain may affect digestibility of feedstuffs and
      should be considered independently or interactively, for some cases, in future
      investigations as sources of variation in AA digestibility.

PMID- 22399731
TI  - Effects of flavomycin and probiotic supplementation to diets containing different
      sources of fat on growth performance, intestinal morphology, apparent
      metabolizable energy, and fat digestibility in broiler chickens.
AB  - This study was conducted with broilers to evaluate the effects of growth
      promoting antibiotic (flavomycin) and probiotic (7 bacterial species)
      supplementation in diets containing soybean oil or free fatty acids (FFA) on
      performance, morphological parameters of the small intestine, apparent
      digestibility of gross energy (GE) in the ileum, and apparent digestibility of
      fat in the ileum and total intestinal tract. Eight-hundred and sixty 4-d-old Ross
      308 broiler chicks were used in a 3 * 3 factorial arrangement of dietary
      treatments that comprised 3 additives (without additive, flavomycin, and
      probiotic) and 3 fat sources (without fat, 30 g/kg of FFA, and 30 g/kg of soybean
      oil) with 4 pen replicates per treatment. All diets contained chromic oxide (3
      g/kg) as an indigestible marker. Body weight and feed intake were recorded weekly
      over 40 d. Flavomycin interacted positively with soybean oil and FFA causing
      improvements (P < 0.05) in BW gain. Among the different fat sources, soybean oil
      significantly increased (P < 0.05) BW gain and jejunal villi height, whereas
      flavomycin improved (P < 0.05) BW gain and feed conversion when compared with the
      remaining dietary additives. However, the probiotic negatively affected (P <
      0.05) BW gain and feed conversion despite increased (P < 0.05) villi heights of
      the duodenum, jejunum, and ileum. At 21 and 38 d of age, fat and GE digestibility
      were higher (P < 0.05) in the ileum and total intestinal tract of birds fed diets
      containing soybean oil than those of birds fed FFA. Fat and GE digestibility were
      highest (P < 0.05) among birds fed flavomycin but lowest (P < 0.05) among
      probiotic-fed birds. Flavomycin addition to soybean oil or FFA diets
      significantly increased (P < 0.05) fat and GE digestibility when compared with
      the same diets containing the probiotic. Therefore, soybean oil is a better
      energy source than FFA, as indicated by increased growth, nutrient digestibility,
      and jejunal villi height. However, probiotic supplementation to fat-rich diets
      caused detrimental effects on nutrient digestibility and growth.

PMID- 22399732
TI  - Phytate and other nutrient components of feed ingredients for poultry.
AB  - Samples of feed ingredients were collected from poultry feed mills in the United
      States and Canada: corn (133), soybean meal (114), corn distillers dried grains
      with solubles (DDGS; 89), bakery by-product meal (95), wheat (22), wheat
      middlings (31), canola meal (21), and wheat shorts (15). The samples were assayed
      by standard wet chemical techniques for CP, fat, neutral detergent fiber (NDF),
      acid detergent fiber, calcium, phosphorus, phytate phosphorus, and ash. There was
      considerable variation found in most of the ingredient components. Forty-two of
      the 64 CV were above 10.0%. The calcium contents of the ingredients were the most
      variable, followed by the fat contents. The CP contents were the least variable.
      There were some fairly consistent relationships observed across samples; in
      general, acid detergent fiber and NDF were positively correlated, as were ash and
      mineral levels. Crude protein and fiber levels were positively related, except
      for wheat shorts, but the relationships were not strong. Phytate P was found to
      be positively related to ash and total P, as expected, except for corn DDGS. The
      fat content of corn was found to be negatively related to the NDF content.
      Significant (P < 0.004) linear regressions were found between phytate P and total
      P for corn, soybean meal, bakery by-product meal, wheat, wheat middlings, and
      wheat shorts. The average nonphytate P content of the ingredients was 49.8%,
      ranging from 38.8% for wheat middlings to 73.2% for DDGS. The phytate P content
      of wheat and wheat by-products could be predicted from their proximate
      compositions, with coefficients of determination in excess of 0.740. Predictions
      for the other ingredients were not as good.

PMID- 22399733
TI  - Effect of selenium sources on the expression of cellular glutathione peroxidase
      and cytoplasmic thioredoxin reductase in the liver and kidney of broiler breeders
      and their offspring.
AB  - In total, 180 Lingnan Yellow broiler breeders were used to investigate the effect
      of different sources of selenium (Se) on the expression of cellular glutathione
      peroxidase (GPx1) and cytoplasmic thioredoxin reductase (TrxR1) in the liver and
      kidney of broiler breeders and their offspring by quantitative real-time PCR.
      There were 6 replicates of 3 dietary treatments. Broiler breeders were fed corn
      soy-based diets supplemented with 0.15 mg/kg of Se from sodium selenite, Se
      enriched yeast (SY), or selenomethionine (SM). At the end of the feeding trial,
      liver and kidney mRNA levels of GPx1 and TrxR1 were determined by quantitative
      real-time PCR, as well as the activity of GPx1 and TrxR1 in liver and kidney of
      breeders and their offspring. The results showed that, compared with sodium
      selenite, SY or SM significantly increased (P < 0.05) the activity of TrxR1 in
      the liver and kidney of broiler breeders and their offspring but not the GPx1
      activity. The liver GPx1 and TrxR1 mRNA levels in SY or SM groups were higher (P
      < 0.05) than that in the sodium selenite group. And the kidney TrxR1 mRNA levels
      were also significantly increased (P < 0.05) by using SY or SM, whereas there was
      no significant difference in the kidney GPx1 mRNA levels between the organic or
      inorganic sources of Se used.

PMID- 22399734
TI  - Effect of xylanase and a blend of essential oils on performance and Salmonella
      colonization of broiler chickens challenged with Salmonella Heidelberg.
AB  - The present experiment examined the influence of xylanase supplementation and a
      blend of essential oils (EO; cinnamaldehyde and thymol) on performance and
      Salmonella horizontal transmission in broiler chickens challenged with
      Salmonella. Two thousand 1-d-old broiler chicks were randomly assigned to 5
      dietary treatments (8 pens/treatment of 50 male broilers each). Four dietary
      treatments were challenged with Salmonella: 1) control, 2) basal diets
      supplemented with EO, 3) basal diet supplemented with xylanase (2,000 U/kg of
      feed), and 4) basal diet supplemented with a combination of EO and xylanase
      (2,000 U/kg of feed). One treatment served as an unchallenged control and was not
      supplemented with either additive. Broiler starter and finisher diets, based on
      wheat and soybean meal, were formulated, pelleted, and fed ad libitum. At d 1,
      before placement, half of the birds from each pen were tagged and dosed with
      Salmonella enterica serovar Heidelberg (5 * 10(5) cfu/mL). On d 42, 5 random
      untagged birds from each pen were killed and their ceca removed and tested for
      Salmonella. Performance data were analyzed as a completely randomized design
      using GLM. The frequency of positive Salmonella in the untagged birds was
      compared between treatments by using a chi-squared test of homogeneity.
      Challenging the birds with Salmonella had no effect (P > 0.05) on any of the
      measured performance parameters. Xylanase and EO supplementation improved (P <
      0.05) the 42-d BW gain and feed efficiency, with no effect (P > 0.05) on feed
      intake, compared with that of the control treatment. Xylanase supplementation
      improved (P < 0.05) BW gain and feed efficiency compared with the results of EO
      supplementation. The combination treatment of xylanase and EO numerically
      improved BW gain and feed efficiency compared with the xylanase treatment.
      Xylanase and EO supplementation reduced (P < 0.05) the incidence of horizontal
      transmission of Salmonella infection between birds by 61 and 77%, respectively,
      compared with the control. The results of the current study suggested that
      dietary addition of EO and xylanase could improve broiler performance and
      contribute to food safety by lowering the incidence of horizontal transmission of
      Salmonella infection.

PMID- 22399735
TI  - The effects of pullet body weight, dietary nonpyhtate phosphorus intake, and
      breeder feeding regimen on production performance, chick quality, and bone
      remodeling in broiler breeders.
AB  - A 3 * 2 * 2 factorial experiment, consisting of 52 hens per treatment, was
      conducted to determine the effects of pullet BW, dietary nonphytate phosphorus
      (NPP), and feeding regimen on performance, progeny quality, and bone remodeling.
      Cobb 500 broiler breeder pullets were reared to 3 different growth curves: 20%
      under, Cobb standard, and 20% over. Body weights were recorded weekly and feed
      adjustments made accordingly. At 21 wk, 624 hens were fed one of 2 breeder diets
      differing only in the amount of dietary NPP: 0.15 or 0.40%. A normal feeding
      regimen was appropriate for the particular growth curve; an alternative regimen
      considered the 3 growth curves together as a flock. At 24, 26, and 29 wk, blood
      was collected from 5 hens per treatment every 4 h over a 24-h period. Plasma
      samples were analyzed for total alkaline phosphatase, tartrate-resistant acid
      phosphatase, parathyroid hormone-related peptide, Ca, and inorganic P. Eggs per
      hen housed were diminished in hens fed the low dietary NPP and by low pullet
      target weight. Hens fed low dietary NPP also had lower egg weights but better
      eggshell quality. Mortality was significantly higher in hens fed low dietary NPP.
      Breeder tibia relative strength and ash were also significantly lower in hens fed
      low dietary NPP, regardless of the quantitative amount. Progeny tibia ash was not
      affected by any treatment. Total alkaline phosphatase responded to pullet BW,
      however by wk 29, total alkaline phosphatase also became sensitive to dietary
      NPP. The NPP by pullet BW interaction for tartrate-resistant acid phosphatase
      levels became significant by 29 wk, and pullet BW was significant at wk 24. The
      NPP by pullet growth curve interaction was also critical for plasma inorganic P
      levels throughout the sampling period. In summary, both 0.15% dietary NPP and
      reared pullets 20% under standard BW negatively affect egg production but do not
      impair progeny productivity. Body composition appears to be a main contributor in
      bone remodeling mechanisms, especially during the transition into egg production.

PMID- 22399736
TI  - A note on sampling digesta from the ileum of broilers in phosphorus digestibility
      studies.
AB  - The responses of broilers to increments of dietary P concentration in P retention
      and P prececal digestibility were studied in 2 experiments using Ross 308
      broilers in their fourth week of age. The low-P basal diet was mainly based on
      corn, potato protein, and corn starch. Titanium dioxide was used as the
      indigestible marker. Monobasic calcium phosphate was added in 6 (experiment 1) or
      5 (experiment 2) graded levels up to a maximum of 8.1 g of P/kg of the diet. Five
      (experiment 1) and 6 (experiment 2) replicated pens of 10 birds were used.
      Excreta were collected from trays underneath the pens. Birds were asphyxiated by
      carbon dioxide exposure and the ileum (from Meckel's diverticulum to 2-cm
      anterior to the ileo-ceca-colonic junction) was dissected. Digesta was collected
      from the entire section (experiment 1) or from 3 subsections of equal lengths
      (experiment 2). Excretion of P increased linearly with increasing dietary P
      concentration up to a level of about 5.2 g of P/kg of the diet and increased
      nonlinearly with further increase in dietary P. In contrast, P flow in the ileum
      increased linearly over the entire range of P intake. Up to the level of 5.2 g of
      P/kg of the diet, P excretion was slightly lower than P flow in the ileum, but
      responses in P excretion and P flow in the ileum were similar, suggesting that P
      excretion with urine is very low and unaffected by P intake when the birds are
      supplied with P below their requirement. Between the 3 subsections of the ileum,
      calculated digestibility was significantly different for the basal diet and the
      diet with the 3 lowest levels of P supplementation. We concluded that the
      response in P prececal digestibility to increments in dietary P concentration is
      linear over a wider range of dietary P than the response in P retention. When
      digesta is collected from the ileum for determination of P prececal
      digestibility, the first third of the ileum should not be considered.

PMID- 22399737
TI  - Identification of differentially expressed genes induced by energy restriction
      using annealing control primer system from the liver and adipose tissues of
      broilers.
AB  - Female Arbor Acre broilers were divided into 2 groups at 18 d of age. One group
      of chickens had free access to feed (AL), and the other group of chickens had 30%
      energy restriction (ER). Adipose and hepatic RNA samples were collected at 48 d
      of age. We employed an accurate reverse-transcription (RT) PCR method that
      involves annealing control primers to identify the differentially expressed genes
      (DEG) between ER and AL groups. Using 20 annealing control primers, 43
      differentially expressed bands (40 downregulated and 3 upregulated in the ER
      group) were detected from the hepatic tissue, whereas no differentially expressed
      bands were detected from the adipose tissue. It seems that energy restriction
      could induce more DEG in hepatic tissue than that in adipose tissue and could
      result in more gene-expression downregulation in hepatic tissue. Eight DEG (6
      known and 2 unknown genes) were gained from hepatic tissue and confirmed by RT
      PCR, which were all supported by released expressed sequence tag sequences. Their
      expressions were all downregulated by energy restriction in hepatic tissues. Six
      known genes are RPL7, RPLP1, FBXL12, ND1, ANTXR2, and SLC22A18, respectively,
      which seem to play essential roles in the protein translation, energy metabolism,
      and tumor inhibition. The alterations of gene expression in 3 selected genes,
      including ND1 (P < 0.01), FBXL12 (P < 0.01), and RPLP1 (P < 0.05), were supported
      by real-time quantitative RT-PCR reaction. Our data provide new insights on the
      metabolic state of broilers changed by energy restriction.

PMID- 22399739
TI  - Reduced O2 concentration during CAM development--its effect on physiological
      parameters of broiler embryos.
AB  - Embryo development is a dynamic process, determined by both the genetic
      background of the organism and the environment in which it develops.
      Environmental alterations during an organism's embryogenesis may induce changes
      in the development of some physiological regulatory systems, thereby causing
      permanent phenotypic changes in the embryo. The present study aimed to assess the
      effect of 17% O(2) concentration during chorioallantoic membrane (CAM)
      development on a) CAM development, b) cardiovascular parameters, and c) embryo
      development postexposure and up to hatch. Two replicated trials, each with 840
      fertile Cobb eggs, were conducted. At embryonic d 5 (E5) eggs were divided into 2
      treatments: 1) control, and 2) 17% O(2) concentration for 12 h/d from E5 through
      E12 (12H). The 12H embryos exhibited a clear and significant increase in the
      vascular area of the CAM, which grew to 6.8% larger than that of the control.
      Hematocrit and hemoglobin levels, as measured on E13 and E14, increased in
      response to the hypoxic treatments, but these differences were not maintained
      subsequently. Heart rate and relative heart weight were not affected by hypoxic
      exposure, but eggshell temperature in the 12H treatment was higher than that of
      the control, indicating higher heat production, which is consistent with the
      elevated plasma concentrations of triiodothyronine and thyroxin and with the
      enhanced oxygen consumption and residual yolk intake rate that followed exposure
      to hypoxic conditions. These findings indicate that embryos adapted to hypoxic
      condition enhance angiogenesis processes, which subsequently increase their blood
      oxygen-carrying capacity, enabling the increase of oxygen consumption, which
      positively affects their growth development and maturation compared with the
      control embryos. Such alterations may affect posthatch performance and the
      ability of broilers cardiovascular system to meet elevated oxygen demand.

PMID- 22399738
TI  - Development and clinical verification of a loop-mediated isothermal amplification
      method for detection of Salmonella species in suspect infected ducks.
AB  - To detect Salmonella spp. in suspect infected ducks, a loop-mediated isothermal
      amplification (LAMP) assay was developed. With the help of this assay, we can
      detect Salmonella enterica serovar Enteriditis and Salmonella enterica serovar
      Anatis above 6.0 cfu/test and 4.8 cfu/test, respectively, in pure-culture
      conditions, even in the existence of 0.01 g of duck liver or spleen homogenates;
      the detection thresholds were still achieved at 6.0 cfu per test tube. Further
      experiments of the test strains indicated the high specificity of this LAMP
      assay. In the detection of clinical specimens, a total of 115 Salmonella suspect
      infected clinical samples was analyzed by traditional culture method, LAMP, and
      PCR. The results suggested that 11 samples were positive by LAMP and culture
      methods; however, only 8 specimens were positive by PCR. In consideration of the
      high sensitivity and fast scanning speed of our LAMP method in clinical
      specimens, it was more suitable for field application and epidemiological
      investigation.

PMID- 22399740
TI  - Electrical waterbath stunning: influence of different waveform and voltage
      settings on the induction of unconsciousness and death in male and female broiler
      chickens.
AB  - Stunning effectiveness of male and female broiler chickens was analyzed in
      response to different waveforms at 3 constant voltage levels. In total, 180 male
      and female broiler chickens were stunned using a sine wave alternating current
      (AC) of 50 Hz, rectangular AC of 70 Hz, and pulsed direct current (DC) of 70 Hz
      (duty-cycle 1:1) with a constant voltage of 60, 80, or 120 V, respectively. In
      each stunning group, 10 male and 10 female birds were stunned for 4 s. The
      current obtained by every bird was recorded. For stunning efficiency, the
      electroencephalogram (EEG) and physical reflexes were recorded and analyzed. The
      EEG was recorded for 120 s poststun. Simultaneously, the occurrence of
      spontaneous eye blinking, wing flapping, and breathing was assessed, and the
      corneal reflex was tested every 20 s poststun. The EEG was analyzed regarding the
      occurrence of a profound suppression to less than 10% of the prestun level in the
      2 to 30 Hz and 13 to 30 Hz bands. Female broilers obtained a significantly lower
      stunning current compared with that of the males. This resulted in a lower
      stunning efficiency for females, when the same constant voltage was applied to
      males and females. The waveforms required different amounts of currents to
      achieve a 90% stunning efficiency. A minimum necessary stunning current of 70,
      90, and 130 mA could be established for sine wave AC, rectangular AC, and pulsed
      DC, respectively. The low stunning efficiency of pulsed DC might be caused by the
      short stunning time of 4 s. This effect should be further investigated for DC
      stunning. Very few birds stunned with AC resumed breathing following stunning,
      indicating stun to kill. Pulsed DC stunning showed a lower effect on the
      induction of death. The level of wing flapping, indicating convulsions and
      possible meat quality defects, was higher for the AC treatments.

PMID- 22399741
TI  - Effects of dietary combination of n-3 and n-9 fatty acids on the deposition of
      linoleic and arachidonic acid in broiler chicken meats.
AB  - To minimize the amount of n-6 fatty acids in broiler chicken meat, 120 Cobb *
      Ross male broilers were divided into 6 different groups and fed a basal corn
      soybean meal diet containing 5% fat from 5 different lipid sources: 1) a
      commercial mix of animal and vegetable oil, 2) soybean oil and olive oil (2.5%
      each), 3) flaxseed oil and olive oil (2.5% each), 4) flaxseed oil,
      eicosapentaenoic acid (C20:5; EPA; n-3), and olive oil (2.45, 0.05, and 2.5%
      respectively; FEO), 5) flaxseed oil, docosahexaenoic acid (C22:6; DHA; n-3), and
      olive oil (2.45, 0.05, and 2.5% respectively; FDO), and 6) fish oil and olive oil
      (2.5% each; FHO). At 6 and 9 wk, one bird per pen (4 pens per treatment) was
      processed, and liver, breast, and thigh samples were collected and used for fatty
      acid profiles or Delta6- and Delta9-desaturase mRNA gene expression levels. The
      deposition of linoleic acid (C18:2; n-6) or arachidonic acid (C20:4; n-6) was
      decreased in breast and thigh muscles of chickens fed n-3 fatty acids for 9 wk
      compared with chickens fed animal and vegetable oil and soybean oil and olive oil
      diets (P < 0.05). The addition of EPA to the diet (FEO; P > 0.05) did not reduce
      the deposition of linoleic acid and arachidonic acid as much as DHA (FDO; P <
      0.05), and it suppressed the expression of Delta6- and Delta9-desaturase. When
      EPA and DHA were blended (FHO) and supplied to broiler chickens for 9 wk, EPA and
      DHA combination effects were observed on the deposition of LA and arachidonic
      acid in breast and thigh muscles. Thereby, the addition of a mixed EPA and DHA to
      a broiler chicken diet may be recommendable to reduce arachidonic acid
      accumulation in both broiler chicken breast and thigh meats, providing a
      functional broiler chicken meat to consumers.

PMID- 22399742
TI  - Effects of propolis on eggshell microbial activity, hatchability, and chick
      performance in Japanese quail (Coturnix coturnix japonica) eggs.
AB  - Propolis is a sticky resin produced by worker honeybees from substances collected
      from plants, and it has strong antibacterial and antifungal properties. The
      purpose of this study was to establish the effects of propolis on egg weight
      loss, hatchability, chick performance, and to control microbial activity
      naturally occurring on eggshells. A total of 750 fresh eggs was randomly divided
      into 5 groups. Eggs from the first group were sprayed with ethyl alcohol (70%,
      A), the second group was sprayed with benzalkonium chloride (B), and the third,
      fourth, and fifth groups were sprayed with propolis at 3 doses: 5, 10, and 15%.
      Eggs sprayed with propolis had lower egg weight loss than eggs from groups A and
      B (P < 0.001). Bacterial activity was reduced significantly in all propolis
      groups. There were no significant differences between treatments for
      hatchability, embryonic mortality, BW gain, and relative growth. Results of the
      present study indicated that propolis could be an alternative hatching egg
      disinfectant versus a chemical disinfectant, without adverse effects on
      hatchability and performance of quail chicks.

PMID- 22399743
TI  - Effect of monochromatic light stimuli during embryogenesis on muscular growth,
      chemical composition, and meat quality of breast muscle in male broilers.
AB  - This study was conducted to evaluate the effect of monochromatic light stimuli
      during embryogenesis on breast muscle growth, chemical composition, and meat
      quality of male broilers. Fertile broiler eggs (Arbor Acres; n = 1,320) were
      preweighed and randomly assigned to 1 of 3 treatment groups in 3 modified
      incubators: 1) control group (in dark condition), 2) monochromatic green light
      group (560 nm), and 3) monochromatic blue light group (480 nm). The monochromatic
      lighting systems sourced from light-emitting diode lamps and were equalized at
      the intensity of 15 lx at eggshell level. After hatch, 120 male chicks from each
      group were placed in 6 replicates with 20 birds each. All of the birds were
      housed under white light (30 lx at bird-head level) with a light schedule of
      23L:1D. At 21, 35, and 42 d of age, BW and breast muscle weight in the green
      light group were significantly increased compared with birds in the blue or dark
      groups (P < 0.05). The breast muscle weight and breast muscle percentages in
      birds incubated under green light were significantly elevated by 50.39 g (0.76%)
      and 54.07 g (1.20%) than those in the dark condition or blue group at 42 d of
      market age (P < 0.05), respectively. In the green light group, feed intake during
      0~42 d was higher than that in the other 2 treatment groups (P < 0.05); feed
      conversion ratio during 0~35 and 0~42 d were lower than that in the dark
      condition (P < 0.05). No significant differences in the contents of breast
      moisture, CP, crude fat, and crude ash among all groups were observed (P > 0.05).
      Green light stimuli tended to increase cooking loss (P = 0.08) and L* value of 24
      h meat color (P = 0.09). These results suggest that green light stimuli during
      embryogenesis enhanced the posthatch BW of male broilers, increased breast muscle
      growth, and improved the feed conversion ratio, but it did not cause any
      noticeable changes in breast chemical composition or overall meat quality
      characteristics.

PMID- 22399744
TI  - An evaluation of the effect of sodium bisulfate as a feed additive on Salmonella
      enterica serotype Enteritidis in experimentally infected broilers.
AB  - The colonization of broiler chickens with Salmonella can pose serious health and
      economic risks for both consumers and the poultry industry. Because colonization
      with Salmonella can lead to subsequent contamination of chicken carcasses during
      processing, preemptive control measures should include the reduction of this
      pathogen in chickens before slaughter. In this study, we evaluated the effect of
      sodium bisulfate, a potential antimicrobial feed additive, on Salmonella
      colonization of experimentally infected broiler chickens. Two hundred and forty 1
      d-old chickens were infected orally with Salmonella enterica serotype Enteritidis
      and divided into 4 groups (each comprised of 60 chickens). Three groups received
      different concentrations of sodium bisulfate integrated into their feed, while
      the feed of the fourth group (positive control) was not treated. At time points
      before the broilers' slaughter age, different organs/tissues (liver, spleen,
      cecum, and bone marrow) and feces were aseptically collected and tested for the
      occurrence and density of Salmonella Enteritidis. Our results show that at 3 d
      postinfection, high colonization with Salmonella Enteritidis was detected and
      affected all tested tissues and fecal samples. Although colonization decreased
      across time, Salmonella Enteritidis persisted in the cecum, feces, spleen, and
      bone marrow, but not in the liver, until slaughter age. Furthermore, the addition
      of sodium bisulfate to the feed did not significantly reduce Salmonella
      Enteritidis numbers in infected chickens or affect the shedding of the pathogen.

PMID- 22399745
TI  - Loxoribine pretreatment reduces Salmonella Enteritidis organ invasion in 1-day
      old chickens.
AB  - Young poultry exhibit a transient colonization by some food-borne pathogens,
      including Salmonella, during the first week of life that stems from immature
      innate and acquired defense mechanisms. Consequently, modulation of the hosts'
      natural immune response is emerging as an important area of interest for food
      animal producers, including the poultry industry. Toll-like receptor (TLR)
      agonists have been shown to boost the innate immune response in young chickens
      and increase their resistance to colonization by Salmonella enterica serovar
      Enteritidis. The objective of the present study was to determine if pretreatment
      with loxoribine, a TLR7 agonist and immune modulator, protects young chicks from
      Salmonella Enteritidis organ invasion. Loxoribine (0-100 MUg) was administered
      intra-abdominally to 1-d-old broiler chicks, and 4 h later, the birds were
      challenged orally with Salmonella Enteritidis. Twenty-four hours postchallenge,
      birds were euthanized and the liver and spleen aseptically removed and cultured
      for Salmonella Enteritidis. This was carried out on 3 separate occasions using 26
      to 50 chicks per dose per experiment. Pretreatment of chicks with loxoribine
      (6.25-25 MUg) significantly (P <= 0.05) reduced liver and spleen organ invasion
      by Salmonella Enteritidis. Higher doses (50-100 MUg) of loxoribine had no effect.
      The results obtained in this study indicate that there is a potential application
      for using loxoribine to increase protection of young chicks when they are most
      susceptible to infections with Salmonella.

PMID- 22399748
TI  - A model of hippocampal competition between new learning and memory updating.

PMID- 22399749
TI  - Imaging synaptic vesicles using VGLUT1-venus knock-in mice: insights into the
      dynamic nature of intersynaptic vesicle exchange.

PMID- 22399750
TI  - Supramodal parametric working memory processing in humans.
AB  - Previous studies of delayed-match-to-sample (DMTS) frequency discrimination in
      animals and humans have succeeded in delineating the neural signature of
      frequency processing in somatosensory working memory (WM). During retention of
      vibrotactile frequencies, stimulus-dependent single-cell and population activity
      in prefrontal cortex was found to reflect the task-relevant memory content,
      whereas increases in occipital alpha activity signaled the disengagement of areas
      not relevant for the tactile task. Here, we recorded EEG from human participants
      to determine the extent to which these mechanisms can be generalized to frequency
      retention in the visual and auditory domains. Subjects performed analogous
      variants of a DMTS frequency discrimination task, with the frequency information
      presented either visually, auditorily, or by vibrotactile stimulation. Examining
      oscillatory EEG activity during frequency retention, we found characteristic
      topographical distributions of alpha power over visual, auditory, and
      somatosensory cortices, indicating systematic patterns of inhibition and
      engagement of early sensory areas, depending on stimulus modality. The task
      relevant frequency information, in contrast, was found to be represented in right
      prefrontal cortex, independent of presentation mode. In each of the three
      modality conditions, parametric modulations of prefrontal upper beta activity (20
      30 Hz) emerged, in a very similar manner as recently found in vibrotactile tasks.
      Together, the findings corroborate a view of parametric WM as supramodal internal
      scaling of abstract quantity information and suggest strong relevance of previous
      evidence from vibrotactile work for a more general framework of quantity
      processing in human working memory.

PMID- 22399751
TI  - Rodents rely on Merkel cells for texture discrimination tasks.
AB  - The cutaneous somatosensory system contains multiple types of mechanoreceptors
      that detect different mechanical stimuli (Johnson, 2001). These stimuli, either
      alone or in combination, are ultimately interpreted by the brain as different
      aspects of the sense of touch. Psychophysical and electrophysiological
      experiments in humans and other mammals implicate one of these mechanoreceptors,
      the Merkel cell/neurite complex, in two-point discrimination and the detection of
      curvature, shape, and texture (Johnson and Lamb, 1981; Johnson et al., 2000;
      Johnson, 2001). However, whether Merkel cell/neurite complex function is required
      for the detection of these stimuli is unknown. We genetically engineered mice
      that lack Merkel cells (Maricich et al., 2009; Morrison et al., 2009) to directly
      test the hypothesis that Merkel cell/neurite complexes are necessary to perform
      these types of sensory discrimination tasks. We found that mice devoid of Merkel
      cells could not detect textured surfaces with their feet while other measures of
      motor and sensory function were unaffected. Interestingly, these mice retained
      the ability to discriminate both texture and shape using their whiskers,
      suggesting that other somatosensory afferents can functionally substitute for
      Merkel cell/neurite complexes in this sensory organ. These findings suggest that
      Merkel cell/neurite complexes are essential for texture discrimination tasks
      involving glabrous skin but not whiskers.

PMID- 22399752
TI  - Accumulation of toxic alpha-synuclein oligomer within endoplasmic reticulum
      occurs in alpha-synucleinopathy in vivo.
AB  - In Parkinson's disease (PD) and other alpha-synucleinopathies, prefibrillar alpha
      synuclein (alphaS) oligomer is implicated in the pathogenesis. However, toxic
      alphaS oligomers observed using in vitro systems are not generally seen to be
      associated with alpha-synucleinopathy in vivo. Thus, the pathologic significance
      of alphaS oligomers to alphaS neurotoxicity is unknown. Herein, we show that,
      alphaS that accumulate within endoplasmic reticulum (ER)/microsome forms toxic
      oligomers in mouse and human brain with the alpha-synucleinopathy. In the mouse
      model of alpha-synucleinopathy, alphaS oligomers initially form before the onset
      of disease and continue to accumulate with the disease progression.
      Significantly, treatment of alphaS transgenic mice with Salubrinal, an anti-ER
      stress compound that delays the onset of disease, reduces ER accumulation of
      alphaS oligomers. These results indicate that alphaS oligomers with toxic
      conformation accumulate in ER, and alphaS oligomer-dependent ER stress is
      pathologically relevant for PD.

PMID- 22399753
TI  - Endoplasmic reticulum stress is important for the manifestations of alpha
      synucleinopathy in vivo.
AB  - Accumulation of misfolded alpha-synuclein (alphaS) is mechanistically linked to
      neurodegeneration in Parkinson's disease (PD) and other alpha-synucleinopathies.
      However, how alphaS causes neurodegeneration is unresolved. Because cellular
      accumulation of misfolded proteins can lead to endoplasmic reticulum
      stress/unfolded protein response (ERS/UPR), chronic ERS could contribute to
      neurodegeneration in alpha-synucleinopathy. Using the A53T mutant human alphaS
      transgenic (A53TalphaS Tg) mouse model of alpha-synucleinopathy, we show that
      disease onset in the alphaS Tg model is coincident with induction of ER
      chaperones in neurons exhibiting alphaS pathology. However, the neuronal ER
      chaperone induction was not accompanied by the activation of phospho-eIF2alpha,
      indicating that alpha-synucleinopathy is associated with abnormal UPR that could
      promote cell death. Induction of ERS/UPR was associated with increased levels of
      ER/microsomal (ER/M) associated alphaS monomers and aggregates. Significantly,
      human PD cases also exhibit higher relative levels of ER/M alphaS than the
      control cases. Moreover, alphaS interacts with ER chaperones and overexpression
      of alphaS sensitizes neuronal cells to ERS-induced toxicity, suggesting that
      alphaS may have direct impact on ER function. This view is supported by the
      presence of ERS-activated caspase-12 and the accumulation of ER-associated
      polyubiquitin. More important, treatment with Salubrinal, an anti-ERS compound,
      significantly attenuates disease manifestations in both the A53TalphaS Tg mouse
      model and the adeno-associated virus-transduced rat model of A53TalphaS-dependent
      dopaminergic neurodegeneration. Our data indicate that the accumulation alphaS
      within ER leads to chronic ER stress conditions that contribute to
      neurodegeneration in alpha-synucleinopathies. Attenuating chronic ERS could be an
      effective therapy for PD and other alpha-synucleinopathies.

PMID- 22399754
TI  - Selective glycine receptor alpha2 subunit control of crossover inhibition between
      the on and off retinal pathways.
AB  - In the retina, the receptive fields (RFs) of almost all ganglion cells (GCs) are
      comprised of an excitatory center and a suppressive surround. The RF center
      arises from local excitatory bipolar cell (BC) inputs and the surround from
      lateral inhibitory inputs. Selective antagonists have been used to define the
      roles of GABA(A) and GABA(C) receptor-mediated input in RF organization. In
      contrast, the role of glycine receptor (GlyR) subunit-specific inhibition is less
      clear because the only antagonist, strychnine, blocks all GlyR subunit
      combinations. We used mice lacking the GlyRalpha2 (Glra2(-/-)) and GlyRalpha3
      (Glra3(-/-)) subunits, or both (Glra2/3(-/-)), to explore their roles in GC RF
      organization. By comparing spontaneous and visually evoked responses of WT with
      Glra2(-/-), Glra3(-/-) and Glra2/3(-/-) ON- and OFF-center GCs, we found that
      both GlyRalpha2 and GlyRalpha3 modulate local RF interactions. In the On pathway,
      both receptors enhance the excitatory center response; however, the underlying
      inhibitory mechanisms differ. GlyRalpha2 participates in crossover inhibition,
      whereas GlyRalpha3 mediates serial inhibition. In the Off pathway, GlyRalpha2
      plays a similar role, again using crossover inhibition and enhancing excitatory
      responses within the RF center. Comparisons of single and double KOs indicate
      that GlyRalpha2 and GlyRalpha3 inhibition are independent and additive,
      consistent with the finding that they use different inhibitory circuitry. These
      findings are the first to define GlyR subunit-specific control of visual function
      and GlyRalpha2 subunit-specific control of crossover inhibition in the retina.

PMID- 22399756
TI  - Coding of apparent motion in the thalamic nucleus of the rat vibrissal
      somatosensory system.
AB  - While exploring objects, rats make multiple contacts using their whiskers,
      thereby generating complex patterns of sensory information. The cerebral
      structures that process this information in the somatosensory system show
      discrete patterns of anatomically distinct units, each corresponding to one
      whisker. Moreover, the feedforward and feedback connections are remarkably
      topographic, with little cross-whisker divergence before reaching the cortical
      network. Despite this parallel design, information processing from several
      whiskers has been reported in subcortical nuclei. Here, we explored whether
      sensory neurons in the ventral posterior medial nucleus (VPM) of the thalamus
      encode emergent properties of complex multiwhisker stimulations. Using a 24
      whisker stimulator, we tested the responses of VPM neurons to sequences of caudal
      deflections that generated an apparent motion in eight different directions
      across the whiskerpad. Overall, 45% of neurons exhibited an evoked increase in
      firing rate significantly selective to the direction of apparent motion of the
      global stimulus. Periods of suppression of firing rate were often observed, but
      were generally not selective. Global motion selectivity of VPM neurons could
      occur regardless of the extent and spatial organization of their receptive
      fields, and of their selectivity for the direction of motion of their principal
      whisker. To investigate whether the global selectivity could be due to
      corticothalamic feedback connections, we inactivated the barrel cortex while
      repeating the stimulation protocol. For most VPM neurons, the direction
      selectivity decreased but was still present. These results suggest that nonlinear
      processing of stimuli from different whiskers emerges in subcortical nuclei and
      is amplified by the corticofugal feedback.

PMID- 22399755
TI  - Critical role of connexin 43 in secondary expansion of traumatic spinal cord
      injury.
AB  - Spinal cord injury (SCI) is often complicated by secondary injury as a result of
      the innate inflammatory response to tissue trauma and swelling. Previous studies
      have shown that excessive ATP release from peritraumatic regions contributes to
      the inflammatory response to SCI by activation of low-affinity P2X7 receptors.
      Because connexin hemichannels constitute an important route for astrocytic ATP
      release, we here evaluated the impact on post-traumatic ATP release of deletion
      of connexins (Cx30/Cx43) in astrocytes. In vivo bioluminescence imaging showed a
      significant reduction in ATP release after weight-drop injury in mice with
      deletion of Cx43 compared with Cx43-expressing littermates, both on a Cx30
      knockout background. Moreover, astrogliosis and microglia activation were reduced
      in peritraumatic areas of those mice lacking Cx43; motor recovery was also
      significantly improved, and the traumatic lesion was smaller. Combined, these
      observations are consistent with a contribution by astrocytic hemichannels to
      post-traumatic ATP release that aggravates secondary injury and restrains
      functional recovery after experimental spinal cord injury. Connexins may thereby
      constitute a new therapeutic target in spinal cord injury.

PMID- 22399757
TI  - FBL2 regulates amyloid precursor protein (APP) metabolism by promoting
      ubiquitination-dependent APP degradation and inhibition of APP endocytosis.
AB  - The ubiquitin-proteasome pathway is a major protein degradation pathway whose
      dysfunction is now widely accepted as a cause of neurodegenerative diseases,
      including Alzheimer's disease. Here we demonstrate that the F-box and leucine
      rich repeat protein2 (FBL2), a component of the E3 ubiquitin ligase complex,
      regulates amyloid precursor protein (APP) metabolism through APP ubiquitination.
      FBL2 overexpression decreased the amount of secreted amyloid beta (Abeta)
      peptides and sAPPbeta, whereas FBL2 mRNA knockdown by siRNA increased these
      levels. FBL2 overexpression also decreased the amount of intracellular Abeta in
      Neuro2a cells stably expressing APP with Swedish mutation. FBL2 bound with APP
      specifically at its C-terminal fragment (CTF), which promoted APP/CTF
      ubiquitination. FBL2 overexpression also accelerated APP proteasome-dependent
      degradation and decreased APP protein localization in lipid rafts by inhibiting
      endocytosis. These effects were not observed in an F-box-deleted FBL2 mutant that
      does not participate in the E3 ubiquitin ligase complex. Furthermore, a reduced
      insoluble Abeta and Abeta plaque burden was observed in the hippocampus of 7
      month-old FBL2 transgenic mice crossed with double-transgenic mice harboring
      APPswe and PS1(M146V) transgenes. These findings indicate that FBL2 is a novel
      and dual regulator of APP metabolism through FBL2-dependent ubiquitination of
      APP.

PMID- 22399758
TI  - Ongoing cortical activity at rest: criticality, multistability, and ghost
      attractors.
AB  - The ongoing activity of the brain at rest, i.e., under no stimulation and in
      absence of any task, is astonishingly highly structured into spatiotemporal
      patterns. These spatiotemporal patterns, called resting state networks, display
      low-frequency characteristics (<0.1 Hz) observed typically in the BOLD-fMRI
      signal of human subjects. We aim here to understand the origins of resting state
      activity through modeling via a global spiking attractor network of the brain.
      This approach offers a realistic mechanistic model at the level of each single
      brain area based on spiking neurons and realistic AMPA, NMDA, and GABA synapses.
      Integrating the biologically realistic diffusion tensor imaging/diffusion
      spectrum imaging-based neuroanatomical connectivity into the brain model, the
      resultant emerging resting state functional connectivity of the brain network
      fits quantitatively best the experimentally observed functional connectivity in
      humans when the brain network operates at the edge of instability. Under these
      conditions, the slow fluctuating (<0.1 Hz) resting state networks emerge as
      structured noise fluctuations around a stable low firing activity equilibrium
      state in the presence of latent "ghost" multistable attractors. The multistable
      attractor landscape defines a functionally meaningful dynamic repertoire of the
      brain network that is inherently present in the neuroanatomical connectivity.

PMID- 22399760
TI  - Magnetoencephalography in twins reveals a strong genetic determination of the
      peak frequency of visually induced gamma-band synchronization.
AB  - Many aspects of brain processing are intimately linked to brain rhythms.
      Essentially all classical brain rhythms, i.e., delta, theta, alpha, beta, and
      sleep waves, are highly heritable. This renders brain rhythms an interesting
      intermediate phenotype for cognitive and behavioral traits. One brain rhythm that
      has been particularly strongly linked to cognition is the gamma rhythm: it is
      involved in attention, short- and long-term memory, and conscious awareness. It
      has been described in sensory and motor cortices, association and control
      structures, and the hippocampus. In contrast to most other brain rhythms, the
      gamma frequency highly depends on stimulus and task conditions, suggesting a low
      heritability. However, the heritability of gamma has not been assessed. Here, we
      show that visually induced gamma-band synchronization in humans is strongly
      genetically determined. Eighty twin subjects (20 monozygotic and 20 dizygotic
      twin pairs) viewed a moving sinusoidal grating while their brain activity was
      recorded using magnetoencephalography. The stimulus induced spectrally confined
      gamma-band activity in sensors over visual cortex in all subjects, with
      individual peak frequencies ranging from 45 to 85 Hz. Gamma-band peak frequencies
      were highly correlated across monozygotic twins (r = 0.88), but not across
      dizygotic twins (r = 0.32) or unrelated subjects (r = 0.02). This implies a
      heritability of the gamma-band frequency of 91%. This strong genetic
      determination suggests that gamma-related cognitive functions are under close
      genetic control.

PMID- 22399759
TI  - Gene expression profiling of neural stem cells and their neuronal progeny reveals
      IGF2 as a regulator of adult hippocampal neurogenesis.
AB  - Neural stem cells (NSCs) generate neurons throughout life in the hippocampal
      dentate gyrus (DG). How gene expression signatures differ among NSCs and immature
      neurons remains largely unknown. We isolated NSCs and their progeny in the adult
      DG using transgenic mice expressing a GFP reporter under the control of the Sox2
      promoter (labeling NSCs) and transgenic mice expressing a DsRed reporter under
      the control of the doublecortin (DCX) promoter (labeling immature neurons).
      Transcriptome analyses revealed distinct gene expression profiles between NSCs
      and immature neurons. Among the genes that were expressed at significantly higher
      levels in DG NSCs than in immature neurons was the growth factor insulin-like
      growth factor 2 (IGF2). We show that IGF2 selectively controls proliferation of
      DG NSCs in vitro and in vivo through AKT-dependent signaling. Thus, by gene
      expression profiling of NSCs and their progeny, we have identified IGF2 as a
      novel regulator of adult neurogenesis.

PMID- 22399761
TI  - Contextual fear memories formed in the absence of the dorsal hippocampus decay
      across time.
AB  - Mammals suffering damage to the hippocampus display a dramatic loss of explicit,
      recently formed memories (retrograde amnesia). In contrast, deficits in the
      ability to form new memories following hippocampal damage (anterograde amnesia)
      can be overcome with sufficient training. By combining contextual fear
      conditioning with lesions of the dorsal hippocampus in rats, we discovered that
      while animals can form long-term contextual fear memories in the absence of the
      hippocampus, these memories decay with time, lacking the permanence that is a
      hallmark characteristic of normal fear memories. These findings indicate that
      while it is initially possible to acquire explicit memories when the hippocampus
      is compromised, these memories cannot transfer from a recent to remote state.
      This suggests that memories formed outside the hippocampus may nevertheless
      require the hippocampus to undergo systems consolidation, which has important
      clinical implications for the treatment of memory disorders.

PMID- 22399762
TI  - A membrane pool retrieved via endocytosis overshoot at nerve terminals: a study
      of its retrieval mechanism and role.
AB  - Endocytosis overshoot, which retrieves more membrane than vesicles just being
      exocytosed, occurs at nerve terminals and non-neuronal secretory cells. The
      mechanism that retrieves the overshoot membrane pool and the role of this pool
      remain largely unknown. We addressed this issue at the rat calyx of Held nerve
      terminal with capacitance measurements. We found that every calyx contained an
      overshoot pool ~1.8 times the readily releasable pool. Retrieval of this pool
      required large calcium influx, and was inhibited by blockers of
      calcium/calmodulin-activated calcineurin and dynamin, suggesting the involvement
      of calcineurin and dynamin in endocytosis overshoot. Depletion of the overshoot
      pool slowed down compensatory endocytosis, whereas recovery of the overshoot pool
      via exocytosis that deposited stranded vesicles to the plasma membrane led to
      recovery of compensatory endocytosis, suggesting that the overshoot pool enhances
      endocytosis efficiency. These results suggest that the overshoot pool exists at
      every nerve terminal, is of limited size arising from vesicles stranded at the
      plasma membrane, is retrieved via calcium/calmodulin/calcineurin and dynamin
      signaling pathway, and can enhance endocytosis efficiency. Potential mechanisms
      for how the endocytosis overshoot pool enhances endocytosis efficiency are
      discussed.

PMID- 22399764
TI  - Efficient "pop-out" visual search elicits sustained broadband gamma activity in
      the dorsal attention network.
AB  - An object that differs markedly from its surrounding-for example, a red cherry
      among green leaves-seems to pop out effortlessly in our visual experience. The
      rapid detection of salient targets, independently of the number of other items in
      the scene, is thought to be mediated by efficient search brain mechanisms. It is
      not clear, however, whether efficient search is actually an "effortless" bottom
      up process or whether it also involves regions of the prefrontal cortex generally
      associated with top-down sustained attention. We addressed this question with
      intracranial EEG (iEEG) recordings designed to identify brain regions underlying
      a classic visual search task and correlate neural activity with target detection
      latencies on a trial-by-trial basis with high temporal precision recordings of
      these regions in epileptic patients. The spatio-temporal dynamics of single-trial
      spectral analysis of iEEG recordings revealed sustained energy increases in a
      broad gamma band (50-150 Hz) throughout the duration of the search process in the
      entire dorsal attention network both in efficient and inefficient search
      conditions. By contrast to extensive theoretical and experimental indications
      that efficient search relies exclusively on transient bottom-up processes in
      visual areas, we found that efficient search is mediated by sustained gamma
      activity in the dorsal lateral prefrontal cortex and the anterior cingulate
      cortex, alongside the superior parietal cortex and the frontal eye field. Our
      findings support the hypothesis that active visual search systematically involves
      the frontal-parietal attention network and therefore, executive attention
      resources, regardless of target saliency.

PMID- 22399763
TI  - Corticotropin releasing factor signaling in the central amygdala is recruited
      during binge-like ethanol consumption in C57BL/6J mice.
AB  - A well established body of work indicates a crucial role for corticotropin
      releasing factor (CRF) in neurobiological responses associated with excessive
      dependence-like ethanol drinking in ethanol-vapor-exposed rodents. Recent
      evidence demonstrates a role for CRF in the modulation of binge-like ethanol
      consumption by nondependent mice, a behavior that can precede ethanol dependence.
      The CRF circuitry that is engaged by binge-like ethanol exposure, however, is
      unknown. Using converging approaches, we provide evidence that, similar to
      ethanol-vapor-induced increases in ethanol intake, CRF signaling in the central
      nucleus of the amygdala (CeA) is engaged during binge-like ethanol consumption by
      C57BL/6J mice. Specifically, we found that binge-like consumption of an ethanol
      solution (20% ethanol v/v) was attenuated by pretreatment with the CRF1R
      antagonists antalarmin, 4-ethyl-[2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)-7H
      pyrrolo[2,3-d]pyrimidin-4-yl]amino-1-butanol, and NBI-27914 at doses (30 mg/kg,
      i.p.) that did not alter nonbinge-like ethanol consumption. Binge-like ethanol
      consumption resulted in significant increases of CRF immunoreactivity in the CeA
      immediately following ethanol drinking and 18-24 h following ethanol removal and
      also blocked the ability of CRF to enhance GABAergic transmission in the CeA 18
      24 h following ethanol removal. Pretreatment with bilateral injections of
      antalarmin (1 MUg/0.5 MUl per side) into the CeA, but not the adjacent
      basolateral amygdala, significantly attenuated binge-like ethanol consumption.
      These findings suggest that CRF signaling in the CeA is recruited during
      excessive ethanol intake, before the development of dependence. We hypothesize
      that plastic changes in CRF signaling develop with repeated binge-like drinking
      episodes, contributing to the transition to dependence.

PMID- 22399765
TI  - Vocal exploration is locally regulated during song learning.
AB  - Exploratory variability is essential for sensorimotor learning, but it is not
      known how and at what timescales it is regulated. We manipulated song learning in
      zebra finches to experimentally control the requirements for vocal exploration in
      different parts of their song. We first trained birds to perform a one-syllable
      song, and once they mastered it, we added a new syllable to the song model.
      Remarkably, when practicing the modified song, birds rapidly alternated between
      high and low acoustic variability to confine vocal exploration to the newly added
      syllable. Furthermore, even within syllables, acoustic variability changed
      independently across song elements that were only milliseconds apart. Analysis of
      the entire vocal output during learning revealed that the variability of each
      song element decreased as it approached the target, correlating with momentary
      local distance from the target and less so with the overall distance within a
      syllable. We conclude that vocal error is computed locally in subsyllabic
      timescales and that song elements can be learned and crystallized independently.
      Songbirds have dedicated brain circuitry for vocal babbling in the anterior
      forebrain pathway (AFP), which generates exploratory song patterns that drive
      premotor neurons at the song nucleus RA. We hypothesize that either AFP adjusts
      the gain of vocal exploration in fine timescales or that the sensitivity of RA
      premotor neurons to AFP/HVC inputs varies across song elements.

PMID- 22399767
TI  - Distinct causal mechanisms of attentional guidance by working memory and
      repetition priming in early visual cortex.
AB  - Human attention may be guided by representations held in working memory (WM) and
      also by priming from implicit memory. Neurophysiological data suggest that WM and
      priming may be associated with distinct neural mechanisms, but this prior
      evidence is only correlative. Furthermore, the role of the visual cortex in
      attention biases from memory remains unclear, because most previous studies
      conflated memory and selection processes. Here, we manipulated memory and
      attention in an orthogonal fashion and used an interventional approach to
      demonstrate the functional significance of WM and priming states in visual cortex
      for attentional biasing. Observers searched for a Landolt target that was
      preceded by a nonpredictive color cue that either had to be held in WM for a
      later recognition test or merely attended (priming counterpart). The application
      of transcranial magnetic stimulation (TMS) over the occipital cortex modulated
      the impact of memory on search. Critically, the direction of this modulation
      depended on the memory state. In the WM condition, the application of TMS on
      validly cued trials (when the cue surrounded the sought target) enhanced search
      accuracy relative to the invalid trials (when the cue surrounded a distracter);
      the opposite pattern was observed in the priming condition. That the effects of
      occipital TMS on selection were contingent on memory context demonstrates that WM
      and priming represent distinct states in the early visual cortex that play a
      causal role in memory-based guidance of attention.

PMID- 22399766
TI  - From salience to saccades: multiple-alternative gated stochastic accumulator
      model of visual search.
AB  - We describe a stochastic accumulator model demonstrating that visual search
      performance can be understood as a gated feedforward cascade from a salience map
      to multiple competing accumulators. The model quantitatively accounts for
      behavior and predicts neural dynamics of macaque monkeys performing visual search
      for a target stimulus among different numbers of distractors. The salience
      accumulated in the model is equated with the spike trains recorded from visually
      responsive neurons in the frontal eye field. Accumulated variability in the
      firing rates of these neurons explains choice probabilities and the distributions
      of correct and error response times with search arrays of different set sizes if
      the accumulators are mutually inhibitory. The dynamics of the stochastic
      accumulators quantitatively predict the activity of presaccadic movement neurons
      that initiate eye movements if gating inhibition prevents accumulation before the
      representation of stimulus salience emerges. Adjustments in the level of gating
      inhibition can control trade-offs in speed and accuracy that optimize visual
      search performance.

PMID- 22399768
TI  - Neural reactivation reveals mechanisms for updating memory.
AB  - Our ability to remember new information is often compromised by competition from
      prior learning, leading to many instances of forgetting. One of the challenges in
      studying why these lapses occur and how they can be prevented is that it is
      methodologically difficult to "see" competition between memories as it occurs.
      Here, we used multi-voxel pattern analysis of human fMRI data to measure the
      neural reactivation of both older (competing) and newer (target) memories during
      individual attempts to retrieve newer memories. Of central interest was the
      following: (1) whether older memories were reactivated during retrieval of newer
      memories; (2) how reactivation of older memories related to retrieval
      performance; and (3) whether neural mechanisms engaged during the encoding of
      newer memories were predictive of neural competition experienced during
      retrieval. Our results indicate that older and newer visual memories were often
      simultaneously reactivated in ventral temporal cortex--even when target memories
      were successfully retrieved. Importantly, stronger reactivation of older memories
      was associated with less accurate retrieval of newer memories, slower mnemonic
      decisions, and increased activity in anterior cingulate cortex. Finally, greater
      activity in the inferior frontal gyrus during the encoding of newer memories
      (memory updating) predicted lower competition in ventral temporal cortex during
      subsequent retrieval. Together, these results provide novel insight into how
      older memories compete with newer memories and specify neural mechanisms that
      allow competition to be overcome and memories to be updated.

PMID- 22399769
TI  - Minocycline-preconditioned neural stem cells enhance neuroprotection after
      ischemic stroke in rats.
AB  - Transplantation of neural stem cells (NSCs) offers a novel therapeutic strategy
      for stroke; however, massive grafted cell death following transplantation,
      possibly due to a hostile host brain environment, lessens the effectiveness of
      this approach. Here, we have investigated whether reprogramming NSCs with
      minocycline, a broadly used antibiotic also known to possess cytoprotective
      properties, enhances survival of grafted cells and promotes neuroprotection in
      ischemic stroke. NSCs harvested from the subventricular zone of fetal rats were
      preconditioned with minocycline in vitro and transplanted into rat brains 6 h
      after transient middle cerebral artery occlusion. Histological and behavioral
      tests were examined from days 0-28 after stroke. For in vitro experiments, NSCs
      were subjected to oxygen-glucose deprivation and reoxygenation. Cell viability
      and antioxidant gene expression were analyzed. Minocycline preconditioning
      protected the grafted NSCs from ischemic reperfusion injury via upregulation of
      Nrf2 and Nrf2-regulated antioxidant genes. Additionally, preconditioning with
      minocycline induced the NSCs to release paracrine factors, including brain
      derived neurotrophic factor, nerve growth factor, glial cell-derived neurotrophic
      factor, and vascular endothelial growth factor. Moreover, transplantation of the
      minocycline-preconditioned NSCs significantly attenuated infarct size and
      improved neurological performance, compared with non-preconditioned NSCs.
      Minocycline-induced neuroprotection was abolished by transfecting the NSCs with
      Nrf2-small interfering RNA before transplantation. Thus, preconditioning with
      minocycline, which reprograms NSCs to tolerate oxidative stress after ischemic
      reperfusion injury and express higher levels of paracrine factors through Nrf2 up
      regulation, is a simple and safe approach to enhance the effectiveness of
      transplantation therapy in ischemic stroke.

PMID- 22399770
TI  - Mechanisms of taste bud cell loss after head and neck irradiation.
AB  - Taste loss in human patients following radiotherapy for head and neck cancer is a
      common and significant problem, but the cellular mechanisms underlying this loss
      are not understood. Taste stimuli are transduced by receptor cells within taste
      buds, and like epidermal cells, taste cells are regularly replaced throughout
      adult life. This renewal relies on progenitor cells adjacent to taste buds, which
      continually supply new cells to each bud. Here we treated adult mice with a
      single 8 Gy dose of x-ray irradiation to the head and neck, and analyzed taste
      epithelium at 1-21 d postirradiation (dpi). We found irradiation targets the
      taste progenitor cells, which undergo cell cycle arrest (1-3 dpi) and apoptosis
      (within 1 dpi). Taste progenitors resume proliferation at 5-7 dpi, with the
      proportion of cells in S and M phase exceeding control levels at 5-6 and 6 dpi,
      respectively, suggesting that proliferation is accelerated and/or synchronized
      following radiation damage. Using 5-bromo-2-deoxyuridine birthdating to identify
      newborn cells, we found that the decreased proliferation following irradiation
      reduces the influx of cells at 1-2 dpi, while the robust proliferation detected
      at 6 dpi accelerates entry of new cells into taste buds. In contrast, the number
      of differentiated taste cells was not significantly reduced until 7 dpi. These
      data suggest a model where continued natural taste cell death, paired with
      temporary interruption of cell replacement, underlies taste loss after
      irradiation.

PMID- 22399771
TI  - The Drosophila visual cycle and de novo chromophore synthesis depends on rdhB.
AB  - In mammalian rods and cones, light activation of the visual pigments leads to
      release of the chromophore, which is then recycled through a multistep enzymatic
      pathway, referred to as the visual or retinoid cycle. In invertebrates such as
      Drosophila, a visual cycle was thought not to exist since the rhodopsins are
      bistable photopigments, which consist of a chromophore that normally stays bound
      to the opsin following light activation. Nevertheless, we recently described a
      visual cycle in Drosophila that serves to recycle the free chromophore that is
      released following light-induced internalization of rhodopsin, and a retinol
      dehydrogenase (RDH) that catalyzes the first step of the pathway. Here, we
      describe the identification of a putative RDH, referred to as RDHB (retinol
      dehydrogenase B), which functions in the visual cycle and in de novo synthesis of
      the chromophore. RDHB was expressed in the retinal pigment cells (RPCs), where it
      promoted the final enzymatic reaction necessary for the production of the
      chromophore. Mutation of rdhB caused moderate light-dependent degeneration of the
      phototransducing compartment of the photoreceptor cells-the rhabdomeres,
      reminiscent of the effects of mutations in some human RDH genes. Since the first
      and last steps in the visual cycle take place in the RPCs, it appears that these
      cells are the sites of action for this entire enzymatic pathway in Drosophila.

PMID- 22399772
TI  - The secreted Wnt antagonist Dickkopf-1 is required for amyloid beta-mediated
      synaptic loss.
AB  - Extensive evidence supports a central role for amyloid-beta (Abeta) in the
      pathogenesis of Alzheimer's disease (AD). Synaptic loss mediated by Abeta in
      early stages of the disease might contribute to cognitive impairments. However,
      little is known about the mechanism by which Abeta induces the loss of synapses.
      The expression of the Wnt antagonist Dickkopf-1 (Dkk1) is increased in brains of
      AD patients and in AD transgenic mouse models, suggesting that dysfunction of Wnt
      signaling could contribute to AD pathology. Here we report that acute exposure to
      Abeta oligomers induces Dkk1 expression together with the loss of synaptic sites.
      Importantly, Dkk1-neutralizing antibodies suppress Abeta-induced synapse loss in
      mouse brain slices. In mature rat hippocampal neurons, Dkk1 decreases the number
      of synapses without affecting cell viability. Ultrastructural analyses revealed
      that Wnt blockade decreases the size of presynaptic and postsynaptic terminals.
      Time-lapse recordings of RFP-labeled stable synaptic sites demonstrate that Dkk1
      induces the dispersal of synaptic components. These findings identify Dkk1 as a
      potential therapeutic target for the treatment of AD.

PMID- 22399773
TI  - Executive control over cognition: stronger and earlier rule-based modulation of
      spatial category signals in prefrontal cortex relative to parietal cortex.
AB  - Human cognition is characterized by flexibility, the ability to select not only
      which action but which cognitive process to engage to best achieve the current
      behavioral objective. The ability to tailor information processing in the brain
      to rules, goals, or context is typically referred to as executive control, and
      although there is consensus that prefrontal cortex is importantly involved, at
      present we have an incomplete understanding of how computational flexibility is
      implemented at the level of prefrontal neurons and networks. To better understand
      the neural mechanisms of computational flexibility, we simultaneously recorded
      the electrical activity of groups of single neurons within prefrontal and
      posterior parietal cortex of monkeys performing a task that required executive
      control of spatial cognitive processing. In this task, monkeys applied different
      spatial categorization rules to reassign the same set of visual stimuli to
      alternative categories on a trial-by-trial basis. We found that single neurons
      were activated to represent spatially defined categories in a manner that was
      rule dependent, providing a physiological signature of a cognitive process that
      was implemented under executive control. We found also that neural signals coding
      rule-dependent categories were distributed between the parietal and prefrontal
      cortex--however, not equally. Rule-dependent category signals were stronger, more
      powerfully modulated by the rule, and earlier to emerge in prefrontal cortex
      relative to parietal cortex. This suggests that prefrontal cortex may initiate
      the switch in neural representation at a network level that is important for
      computational flexibility.

PMID- 22399775
TI  - Neurofibromin modulates adult hippocampal neurogenesis and behavioral effects of
      antidepressants.
AB  - Neurogenesis persists in the rodent dentate gyrus (DG) throughout adulthood but
      declines with age and stress. Neural progenitor cells (NPCs) residing in the
      subgranular zone of the DG are regulated by an array of growth factors and
      respond to the microenvironment, adjusting their proliferation level to determine
      the rate of neurogenesis. Here we report that genetic deletion of neurofibromin
      (Nf1), a tumor suppressor with RAS-GAP activity, in adult NPCs enhanced DG
      proliferation and increased generation of new neurons in mice. Nf1 loss
      associated neurogenesis had the functional effect of enhancing behavioral
      responses to subchronic antidepressants and, over time, led to spontaneous
      antidepressive-like behaviors. Thus, our findings establish an important role for
      the Nf1-Ras pathway in regulating adult hippocampal neurogenesis, and demonstrate
      that activation of adult NPCs is sufficient to modulate depression- and anxiety
      like behaviors.

PMID- 22399774
TI  - Identification of modulators of hair cell regeneration in the zebrafish lateral
      line.
AB  - The external location of the zebrafish lateral line makes it a powerful model for
      studying mechanosensory hair cell regeneration. We have developed a chemical
      screen to identify FDA-approved drugs and biologically active compounds that
      modulate hair cell regeneration in zebrafish. Of the 1680 compounds evaluated, we
      identified two enhancers and six inhibitors of regeneration. The two enhancers,
      dexamethasone and prednisolone, are synthetic glucocorticoids that potentiated
      hair cell numbers during regeneration and also induced hair cell addition in the
      absence of damage. BrdU analysis confirmed that the extra hair cells arose from
      mitotic activity. We found that dexamethasone and prednisolone, like other
      glucocorticoids, suppress zebrafish caudal fin regeneration, indicating that hair
      cell regeneration occurs by a distinctly different process. Further analyses of
      the regeneration inhibitors revealed that two of the six, flubendazole and
      topotecan, significantly suppress hair cell regeneration by preventing
      proliferation of hair cell precursors. Flubendazole halted support cell division
      in M-phase, possibly by interfering with normal microtubule activity. Topotecan,
      a topoisomerase inhibitor, killed both hair cells and proliferating hair cell
      precursors. A third inhibitor, fulvestrant, moderately delayed hair cell
      regeneration by reducing support cell proliferation. Our observation that hair
      cells do not regenerate when support cell proliferation is impeded confirms
      previous observations that cell division is the primary route for hair cell
      regeneration after neomycin treatment in zebrafish.

PMID- 22399776
TI  - Hippocampal dynamics predict interindividual cognitive differences in rats.
AB  - There are important and sustained interindividual differences in cognition during
      aging. Here, we investigated hippocampal spatial representations in a rat model
      of cognitive aging characterized by individual differences in a mnemonic task.
      Individual cognitive capabilities in old rats were assessed in a delayed non
      matching-to-position task. We recorded hippocampal CA1 place cells as the rats
      explored a familiar environment. Unlike the usual place cells commonly described
      in the literature, we found that a significant fraction of pyramidal neurons
      recorded in our study showed a substantial delayed onset of their place field
      activity. We established that this firing onset delay naturally occurs under
      basal conditions in old rats and is positively correlated with the remapping
      status of the animals. The lack of firing during the first few hundred seconds
      after the animals were introduced into a familiar environment was also associated
      with an increased locomotion in the remapping rats. This delayed activity is
      central to understanding the individual basis of age-related cognitive impairment
      and to resolving numerous discrepancies in the literature on the place cell
      contribution to the etiology of aged-related decline. Finally, we also found a
      positive correlation between the degree of firing variability of place cells
      ("overdispersion") and performance during the long delays in the delayed non
      matching-to-position task. Place cell overdispersion might provide the functional
      basis for interindividual differences in behavior and cognition.

PMID- 22399777
TI  - Gap-junctional coupling of mammalian rod photoreceptors and its effect on visual
      detection.
AB  - The presence of gap junctions between rods in mammalian retina suggests a role
      for rod-rod coupling in human vision. Rod coupling is known to reduce response
      variability, but because junctional conductances are not known, the downstream
      effects on visual performance are uncertain. Here we assessed rod coupling in
      guinea pig retina by measuring: (1) the variability in responses to dim flashes,
      (2) Neurobiotin tracer coupling, and (3) junctional conductances. Results were
      consolidated into an electrical network model and a model of human psychophysical
      detection. Guinea pig rods form tracer pools of 1 to ~20 rods, with junctional
      conductances averaging ~350 pS. We calculate that coupling will reduce human dark
      adapted sensitivity ~10% by impairing the noise filtering of the synapse between
      rods and rod bipolar cells. However, coupling also mitigates synaptic saturation
      and is thus calculated to improve sensitivity when stimuli are spatially
      restricted or are superimposed over background illumination.

PMID- 22399778
TI  - Heterogeneous nuclear ribonucleoprotein K, an RNA-binding protein, is required
      for optic axon regeneration in Xenopus laevis.
AB  - Axotomized optic axons of Xenopus laevis, in contrast to those of mammals, retain
      their ability to regenerate throughout life. To better understand the molecular
      basis for this successful regeneration, we focused on the role of an RNA-binding
      protein, heterogeneous nuclear ribonucleoprotein (hnRNP) K, because it is
      required for axonogenesis during development and because several of its RNA
      targets are under strong post-transcriptional control during regeneration. At 11
      d after optic nerve crush, hnRNP K underwent significant translocation into the
      nucleus of retinal ganglion cells (RGCs), indicating that the protein became
      activated during regeneration. To suppress its expression, we intravitreously
      injected an antisense Vivo-Morpholino oligonucleotide targeting hnRNP K. In
      uninjured eyes, it efficiently knocked down hnRNP K expression in only the RGCs,
      without inducing either an axotomy response or axon degeneration. After optic
      nerve crush, staining for multiple markers of regenerating axons showed no
      regrowth of axons beyond the lesion site with hnRNP K knockdown. RGCs nonetheless
      responded to the injury by increasing expression of multiple growth-associated
      RNAs and experienced no additional neurodegeneration above that normally seen
      with optic nerve injury. At the molecular level, hnRNP K knockdown during
      regeneration inhibited protein, but not mRNA, expression of several known hnRNP K
      RNA targets (NF-M, GAP-43) by compromising their efficient nuclear transport and
      disrupting their loading onto polysomes for translation. Our study therefore
      provides evidence of a novel post-transcriptional regulatory pathway orchestrated
      by hnRNP K that is essential for successful CNS axon regeneration.

PMID- 22399779
TI  - Dissociating modality-specific and supramodal neural systems for action
      understanding.
AB  - The neural basis of action understanding in humans remains disputed, with some
      research implicating the putative mirror neuron system (MNS) and some a
      mentalizing system (MZS) for inferring mental states. The basis for this dispute
      may be that action understanding is a heterogeneous construct: actions can be
      understood from sensory information about body movements or from language about
      action, and with the goal of understanding the implementation ("how") or motive
      ("why") of an action. Although extant research implicates the MNS in
      understanding implementation and the MZS in understanding motive, it remains
      unknown to what extent these systems subserve modality-specific or supramodal
      functions in action understanding. While undergoing fMRI, 21 volunteers
      considered the implementation ("How is she doing it?") and motive ("Why is she
      doing it?") for actions presented in video or text. Bilateral parietal and right
      frontal areas of the MNS showed a modality-specific association with perceiving
      actions in videos, while left-hemisphere MNS showed a supramodal association with
      understanding implementation. Largely left-hemisphere MZS showed a supramodal
      association with understanding motive; however, connectivity among the MZS and
      MNS during the inference of motive was modality specific, being significantly
      stronger when motive was understood from actions in videos compared to text.
      These results support a tripartite model of MNS and MZS contributions to action
      understanding, where distinct areas of the MNS contribute to action perception
      ("perceiving what") and the representation of action implementation ("knowing
      how"), while the MZS supports an abstract, modality-independent representation of
      the mental states that explain action performance ("knowing why").

PMID- 22399781
TI  - MPs insist that NHS whistleblowers are protected.

PMID- 22399782
TI  - Millennium development goal met early on access to safe water.

PMID- 22399780
TI  - Visual working memory capacity and the medial temporal lobe.
AB  - Patients with medial temporal lobe (MTL) damage are sometimes impaired at
      remembering visual information across delays as short as a few seconds. Such
      impairments could reflect either impaired visual working memory capacity or
      impaired long-term memory (because attention has been diverted or because working
      memory capacity has been exceeded). Using a standard change-detection task, we
      asked whether visual working memory capacity is intact or impaired after MTL
      damage. Five patients with hippocampal lesions and one patient with large MTL
      lesions saw an array of 1, 2, 3, 4, or 6 colored squares, followed after 3, 4, or
      8 s by a second array where one of the colored squares was cued. The task was to
      decide whether the cued square had the same color as the corresponding square in
      the first array or a different color. At the 1 s delay typically used to assess
      working memory capacity, patients performed as well as controls at all array
      sizes. At the longer delays, patients performed as well as controls at small
      array sizes, thought to be within the capacity limit, and worse than controls at
      large array sizes, thought to exceed the capacity limit. The findings suggest
      that visual working memory capacity in humans is intact after damage to the MTL
      structures and that damage to these structures impairs performance only when
      visual working memory is insufficient to support performance.

PMID- 22399783
TI  - Functional diversity of bitter taste receptor TAS2R16 in primates.
AB  - In mammals, bitter taste is mediated by TAS2R genes, which belong to the large
      family of seven transmembrane G protein-coupled receptors. Because TAS2Rs are
      directly involved in the interaction between mammals and their dietary sources,
      it is likely that these genes evolved to reflect species-specific diets during
      mammalian evolution. Here, we investigated the sensitivities of TAS2R16s of
      various primates by using a cultured cell expression system, and found that the
      sensitivity of each primate species varied according to the ligand. Especially,
      the sensitivity of TAS2R16 of Japanese macaques to salicin was much lower than
      that of human TAS2R16, which was supported by behavioural tests. These results
      suggest the possibility that bitter-taste sensitivities evolved independently by
      replacing specific amino acid residues of TAS2Rs in different primate species to
      adapt to food items they use.

PMID- 22399784
TI  - Speed, pacing strategy and aerodynamic drafting in Thoroughbred horse racing.
AB  - Choice of pacing strategy and the benefit of aerodynamic drafting are thought to
      be key determinants of racing performance. These effects have largely been
      analysed without reference to final outcome, in small datasets with low temporal
      resolution, and a focus on human swimming, cycling and running. Here, we
      determined the position and speed of 44,803 racehorses, once per second, in 3,357
      races ranging in length from 1006 to 4225 m (50.9-292.9 seconds duration) using a
      validated radio tracking system. We find that aerodynamic drafting has a marked
      effect on horse performance, and hence racing outcome. Furthermore, we
      demonstrate that race length-dependent pacing strategies are correlated with the
      fastest racing times, with some horses reaching a maximum speed in excess of 19 m
      s(-1). The higher speeds seen with certain pacing strategies may arise due to the
      nature of pack racing itself, or may be a reflection of individual capabilities,
      that is, corresponding to horses that perform well in roles suited to their
      'front-running' or 'chaser' personality traits.

PMID- 22399785
TI  - Rollers smell the fear of nestlings.
AB  - Many animals react to danger by producing chemical cues that can be smelled by
      others, which is called the smell of fear. Some bird species produce chemical
      compounds when threatened, such as nestlings of the Eurasian roller Coracias
      garrulus that vomit an odorous orange liquid when scared in their nests. Here, we
      experimentally explore the possibility that parents were informed about recent
      predation attempts at their nests through the olfaction of this vomit. Parents of
      nests treated with nestling vomit delayed their entrance to nests and decreased
      their provisioning rate in comparison with parents of nests treated with an
      odorous control. These results demonstrate that adult rollers are able to smell
      the fear of offspring and show for the first time in birds that a scent produced
      during an interspecific challenge has a role in an intraspecific communication
      scenario.

PMID- 22399786
TI  - RNAi of the circadian clock gene period disrupts the circadian rhythm but not the
      circatidal rhythm in the mangrove cricket.
AB  - The clock mechanism for circatidal rhythm has long been controversial, and its
      molecular basis is completely unknown. The mangrove cricket, Apteronemobius
      asahinai, shows two rhythms simultaneously in its locomotor activity: a
      circatidal rhythm producing active and inactive phases as well as a circadian
      rhythm modifying the activity intensity of circatidal active phases. The role of
      the clock gene period (per), one of the key components of the circadian clock in
      insects, was investigated in the circadian and circatidal rhythms of A. asahinai
      using RNAi. After injection of double-stranded RNA of per, most crickets did not
      show the circadian modulation of activity but the circatidal rhythm persisted
      without a significant difference in the period from controls. Thus, per is
      functionally involved in the circadian rhythm but plays no role, or a less
      important role, in the circatidal rhythm. We conclude that the circatidal rhythm
      in A. asahinai is controlled by a circatidal clock whose molecular mechanism is
      different from that of the circadian clock.

PMID- 22399787
TI  - Winter severity predicts the timing of host shifts in the mosquito Culex
      erraticus.
AB  - In temperate regions, seasonal epidemics of many mosquito-borne viruses are
      triggered when mosquito populations shift from feeding on avian to mammalian
      hosts. We investigated effects of temperature on the timing of bird-to-mammal
      shifts using an 8 year dataset of blood-meals from a mosquito (Culex erraticus)
      in Alabama, USA. As expected, Cx. erraticus shifted from avian to mammalian hosts
      each year. The timing of the shift, however, varied considerably among years.
      Harshness of the preceding winter (chill accumulation) explained 93 per cent of
      the variation in the timing of bird-to-mammal shifts, with shifts occurring later
      in years following harsher winters. We hypothesize that winter temperatures drive
      the timing of bird-to-mammal shifts through effects on host reproductive
      phenology. Because mosquitoes target birds during the nesting season, and bird
      nesting occurs later in years following colder winters, later nesting dates
      result in a concomitant delay in the timing of bird-to-mammal host shifts. Global
      increases in winter temperatures could cause significant changes in the timing of
      seasonal host shifts by mosquitoes, with prolonged periods of epidemic
      transmission of mosquito-borne diseases.

PMID- 22399788
TI  - Osteogenic differentiation and mineralization in fibre-reinforced tubular
      scaffolds: theoretical study and experimental evidences.
AB  - The development of composite scaffolds with well-organized architecture and multi
      scale properties (i.e. porosity, degradation) represents a valid approach for
      achieving a tissue-engineered construct capable of reproducing the medium- and
      long-term in vitro behaviour of hierarchically complex tissues such as spongy
      bone. To date, the implementation of scaffold design strategies able to summarize
      optimal scaffold architecture as well as intrinsic mechanical, chemical and fluid
      transport properties still remains a challenging issue. In this study, poly
      epsilon-caprolactone/polylactid acid (PCL/PLA) tubular devices (fibres of PLA in
      a PCL matrix) obtained by phase inversion/salt leaching and filament winding
      techniques were proposed as cell instructive scaffold for bone osteogenesis.
      Continuous fibres embedded in the polymeric matrix drastically improved the
      mechanical response as confirmed by compression elastic moduli, which vary from
      0.214 +/- 0.065 to 1.174 +/- 0.143 MPa depending on the relative fibre/matrix and
      polymer/solvent ratios. Moreover, computational fluid dynamic simulations
      demonstrated the ability of composite structure to transfer hydrodynamic forces
      during in vitro culture, thus indicating the optimal flow rate conditions that,
      case by case, enables specific cellular events-i.e. osteoblast differentiation
      from human mesenchymal stem cells (hMSCs), mineralization, etc. Hence, we
      demonstrate that the hMSC differentiation preferentially occurs in the case of
      higher perfusion rates-over 0.05 ml min(-1)-as confirmed by the expression of
      alkaline phosphate and osteocalcin markers. In particular, the highest
      osteopontin values and a massive mineral phase precipitation of bone-like phases
      detected in the case of intermediate flow rates (i.e. 0.05 ml min(-1)) allows us
      to identify the best condition to stimulate the bone extracellular matrix in
      growth, in agreement with the hydrodynamic model prediction. All these results
      concur to prove the succesful use of tubular composite as temporary device for
      long bone treatment.

PMID- 22399789
TI  - Virtual experiments, physical validation: dental morphology at the intersection
      of experiment and theory.
AB  - Computational models such as finite-element analysis offer biologists a means of
      exploring the structural mechanics of biological systems that cannot be directly
      observed. Validated against experimental data, a model can be manipulated to
      perform virtual experiments, testing variables that are hard to control in
      physical experiments. The relationship between tooth form and the ability to
      break down prey is key to understanding the evolution of dentition. Recent
      experimental work has quantified how tooth shape promotes fracture in biological
      materials. We present a validated finite-element model derived from physical
      compression experiments. The model shows close agreement with strain patterns
      observed in photoelastic test materials and reaction forces measured during these
      experiments. We use the model to measure strain energy within the test material
      when different tooth shapes are used. Results show that notched blades deform
      materials for less strain energy cost than straight blades, giving insights into
      the energetic relationship between tooth form and prey materials. We identify a
      hypothetical 'optimal' blade angle that minimizes strain energy costs and test
      alternative prey materials via virtual experiments. Using experimental data and
      computational models offers an integrative approach to understand the mechanics
      of tooth morphology.

PMID- 22399790
TI  - Microbial synthesis of core/shell gold/palladium nanoparticles for applications
      in green chemistry.
AB  - We report a novel biochemical method based on the sacrificial hydrogen strategy
      to synthesize bimetallic gold (Au)-palladium (Pd) nanoparticles (NPs) with a
      core/shell configuration. The ability of Escherichia coli cells supplied with
      H(2) as electron donor to rapidly precipitate Pd(II) ions from solution is used
      to promote the reduction of soluble Au(III). Pre-coating cells with Pd(0) (bioPd)
      dramatically accelerated Au(III) reduction, with the Au(III) reduction rate being
      dependent upon the initial Pd loading by mass on the cells. Following Au(III)
      addition, the bioPd-Au(III) mixture rapidly turned purple, indicating the
      formation of colloidal gold. Mapping of bio-NPs by energy dispersive X-ray
      microanalysis suggested Au-dense core regions and peripheral Pd but only Au was
      detected by X-ray diffraction (XRD) analysis. However, surface analysis of
      cleaned NPs by cyclic voltammetry revealed large Pd surface sites, suggesting,
      since XRD shows no crystalline Pd component, that layers of Pd atoms surround Au
      NPs. Characterization of the bimetallic particles using X-ray absorption
      spectroscopy confirmed the existence of Au-rich core and Pd-rich shell type
      bimetallic biogenic NPs. These showed comparable catalytic activity to chemical
      counterparts with respect to the oxidation of benzyl alcohol, in air, and at a
      low temperature (90 degrees C).

PMID- 22399791
TI  - Amyotrophic lateral sclerosis and frontotemporal dementia.

PMID- 22399792
TI  - Road to the chromosome 9p-linked ALS/FTD locus.

PMID- 22399794
TI  - Absence of consensus in diagnostic criteria for familial neurodegenerative
      diseases.
AB  - BACKGROUND: A small proportion of cases seen in neurodegenerative conditions such
      as amyotrophic lateral sclerosis (ALS), Parkinson's disease and Alzheimer disease
      are familial. These familial cases are usually clinically indistinguishable from
      sporadic cases. Identifying familial cases is important both in terms of clinical
      guidance for family members and for gene discovery. METHOD: Surveys assessing the
      definition of familial amyotrophic lateral sclerosis (FALS) were completed by
      clinicians with an interest in ALS. RESULTS: 95 surveys were completed by
      respondents from 15 countries. A third of total respondents stated that they
      thought that neurologists were using the same definition for FALS (33.3%, 30). No
      consensus was achieved among clinicians when provided with five different
      definitions for FALS. However, the preferred definition was 'a patient with ALS
      with either a first or second degree relative also with ALS' (37.8%, 31).
      CONCLUSION: There is no consensus on a standard definition for FALS among
      clinicians. It is likely that similar inconsistencies apply to other conditions,
      such as Parkinson's disease and Alzheimer disease, in which both familial and
      sporadic diseases occur. Inconsistent classification could hinder gene discovery.

PMID- 22399793
TI  - Atypical, slowly progressive behavioural variant frontotemporal dementia
      associated with C9ORF72 hexanucleotide expansion.
AB  - BACKGROUND: Some patients meeting behavioural variant frontotemporal dementia
      (bvFTD) diagnostic criteria progress slowly and plateau at mild symptom severity.
      Such patients have mild neuropsychological and functional impairments, lack
      characteristic bvFTD brain atrophy and have thus been referred to as bvFTD
      'phenocopies' or slowly progressive (bvFTD-SP). The few patients with bvFTD-SP
      that have been studied at autopsy have demonstrated no evidence of FTD pathology,
      suggesting that bvFTD-SP is neuropathologically distinct from other forms of FTD.
      Here, two patients with bvFTD-SP with chromosome 9 open reading frame 72
      (C9ORF72) hexanucleotide expansions are described. METHODS: 384 patients with an
      FTD clinical spectrum and Alzheimer's disease diagnoses were screened for C9ORF72
      expansion. Two bvFTD-SP mutation carriers were identified. Neuropsychological and
      functional data, as well as brain atrophy patterns, assessed using voxel based
      morphometry (VBM), were compared with 44 patients with sporadic bvFTD and 85
      healthy controls. RESULTS: Both patients were aged 48 years at baseline and met
      possible bvFTD criteria. In the first patient, VBM revealed thalamic and
      posterior insula atrophy. Over 7 years, his neuropsychological performance and
      brain atrophy remained stable. In the second patient, VBM revealed cortical
      atrophy with subtle frontal and insular volume loss. Over 2 years, her
      neuropsychological and functional scores as well as brain atrophy remained
      stable. CONCLUSIONS: C9ORF72 mutations can present with a bvFTD-SP phenotype.
      Some bvFTD-SP patients may have neurodegenerative pathology, and C9ORF72
      mutations should be considered in patients with bvFTD-SP and a family history of
      dementia or motor neuron disease.

PMID- 22399795
TI  - The changing landscape of non-invasive ventilation in amyotrophic lateral
      sclerosis.

PMID- 22399796
TI  - Nerve fibre degeneration in the brain in amyotrophic lateral sclerosis.

PMID- 22399797
TI  - Physical fitness and amyotrophic lateral sclerosis: dangerous liaisons or common
      genetic pathways?

PMID- 22399798
TI  - Plk2 regulates centriole duplication through phosphorylation-mediated degradation
      of Fbxw7 (human Cdc4).
AB  - Polo-like kinases (Plks) perform crucial functions during mitosis, cytokinesis
      and centriole duplication. Plk2 is activated in early G1 phase and is involved in
      the reproduction of centrosomes. However, the mechanisms underlying Plk2-induced
      centriole duplication are incompletely understood. Here, we show that Plk2
      directly targets the F-box protein F-box/WD repeat-containing protein 7 (Fbxw7),
      which is a regulator of the ubiquitin-mediated degradation of cyclin E. Plk2
      phosphorylates Fbxw7 on serine 176 and the two proteins form a complex in vitro
      and in vivo. Phosphorylation of Fbxw7 by Plk2 induces destabilization of the F
      box protein resulting in accumulation of cyclin E and increased potential for
      centriole reproduction. In addition, loss of Fbxw7 in human cells leads to
      uncontrolled centriole duplication, highlighting the importance of Fbxw7
      regulation by Plk2. These findings define a previously unknown Plk2-dependent
      pathway involved at the onset of S phase and in centrosome duplication.

PMID- 22399799
TI  - A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1
      CoREST complex through the dimethylation of its SNAG domain.
AB  - Gfi-1B is a transcriptional repressor essential for the regulation of
      erythropoiesis and megakaryopoiesis. Here we identify Gfi-1B p32, a Gfi-1B
      isoform, as essential for erythroid differentiation. Gfi-1B p32 is generated by
      alternative splicing and lacks the two first zinc finger domains of the protein.
      Selective knock down of Gfi-1B p32 compromises erythroid differentiation, whereas
      its ectopic expression induces erythropoiesis in the absence of erythropoietin.
      Gfi-1B p32 isoform binds to Gfi-1B target gene promoters and associates with the
      LSD1-CoREST repressor complex more efficiently than the major Gfi-1B p37 isoform.
      Furthermore, we show that Gfi-1B includes a KSKK motif in its SNAG domain, which
      recruits the repressor complex only when dimethylated on lysine 8. Mutation of
      lysine 8 prevents Gfi-1B p32-induced erythroid development. Our results thus
      highlight a key role for the alternatively spliced Gfi-1B p32 isoform in
      erythroid development.

PMID- 22399801
TI  - Wiring through tunneling nanotubes--from electrical signals to organelle
      transfer.
AB  - Tunneling nanotubes (TNTs) represent a subset of F-actin-based transient tubular
      connections that allow direct communication between distant cells. Recent studies
      have provided new insights into the existence of TNTs in vivo, and this novel
      mechanism of intercellular communication is implicated in various essential
      processes, such as development, immunity, tissue regeneration and transmission of
      electrical signals. TNTs are versatile structures known to facilitate the
      transfer of various cargos, such as organelles, plasma membrane components,
      pathogens and Ca(2+). Recently, a new function of TNTs in the long-range transfer
      of electrical signals that involves gap junctions has been suggested. This
      indicates that different types of TNTs might exist, and supports the notion that
      TNTs might not be just passive open conduits but rather are regulated by gating
      mechanisms. Furthermore, TNTs have been found in different cell lines and are
      characterized by their diversity in terms of morphology. Here we discuss these
      novel findings in the context of the two models that have been proposed for TNT
      formation, and focus on putative proteins that could represent TNT specific
      markers. We also shed some light on the molecular mechanisms used by TNTs to
      transfer cargos, as well as chemical and electrical signals.

PMID- 22399800
TI  - The endonuclease Ankle1 requires its LEM and GIY-YIG motifs for DNA cleavage in
      vivo.
AB  - The LEM domain (for lamina-associated polypeptide, emerin, MAN1 domain) defines a
      group of nuclear proteins that bind chromatin through interaction of the LEM
      motif with the conserved DNA crosslinking protein, barrier-to-autointegration
      factor (BAF). Here, we describe a LEM protein annotated in databases as 'Ankyrin
      repeat and LEM domain-containing protein 1' (Ankle1). We show that Ankle1 is
      conserved in metazoans and contains a unique C-terminal GIY-YIG motif that
      confers endonuclease activity in vitro and in vivo. In mammals, Ankle1 is
      predominantly expressed in hematopoietic tissues. Although most characterized LEM
      proteins are components of the inner nuclear membrane, ectopic Ankle1 shuttles
      between cytoplasm and nucleus. Ankle1 enriched in the nucleoplasm induces DNA
      cleavage and DNA damage response. This activity requires both the catalytic C
      terminal GIY-YIG domain and the LEM motif, which binds chromatin via BAF. Hence,
      Ankle1 is an unusual LEM protein with a GIY-YIG-type endonuclease activity in
      higher eukaryotes.

PMID- 22399802
TI  - In vivo fluorescence resonance energy transfer imaging reveals differential
      activation of Rho-family GTPases in glioblastoma cell invasion.
AB  - Two-photon excitation microscopy was used to visualized two different modes of
      invasion at perivascular and intraparenchymal regions of rat C6 glioblastoma
      cells that were orthotopically implanted into rat brains. Probes based on the
      principle of Forster resonance energy transfer (FRET) further revealed that
      glioblastoma cells penetrating the brain parenchyma showed higher Rac1 and Cdc42
      activities and lower RhoA activity than those advancing in the perivascular
      regions. This spatial regulation of Rho-family GTPase activities was
      recapitulated in three-dimensional spheroid invasion assays with rat and human
      glioblastoma cells, in which multipod glioblastoma cells that invaded the gels
      and led the other glioblastoma cells exhibited higher Rac1 and Cdc42 activities
      than the trailing glioblastoma cells. We also studied the Cdc42-specific guanine
      nucleotide exchange factor Zizimin1 (also known as DOCK9) as a possible
      contributor to this spatially controlled activation of Rho-family GTPases,
      because it is known to play an essential role in the extension of neurites. We
      found that shRNA-mediated knockdown of Zizimin1 inhibited formation of
      pseudopodia and concomitant invasion of glioblastoma cells both under a 3D
      culture condition and in vivo. Our results suggest that the difference in the
      activity balance of Rac1 and Cdc42 versus RhoA determines the mode of
      glioblastoma invasion and that Zizimin1 contributes to the invasiveness of
      glioblastoma cells with high Rac1 and Cdc42 activities.

PMID- 22399803
TI  - Kinetochores accelerate centrosome separation to ensure faithful chromosome
      segregation.
AB  - At the onset of mitosis, cells need to break down their nuclear envelope, form a
      bipolar spindle and attach the chromosomes to microtubules via kinetochores.
      Previous studies have shown that spindle bipolarization can occur either before
      or after nuclear envelope breakdown. In the latter case, early kinetochore
      microtubule attachments generate pushing forces that accelerate centrosome
      separation. However, until now, the physiological relevance of this prometaphase
      kinetochore pushing force was unknown. We investigated the depletion phenotype of
      the kinetochore protein CENP-L, which we find to be essential for the stability
      of kinetochore microtubules, for a homogenous poleward microtubule flux rate and
      for the kinetochore pushing force. Loss of this force in prometaphase not only
      delays centrosome separation by 5-6 minutes, it also causes massive chromosome
      alignment and segregation defects due to the formation of syntelic and merotelic
      kinetochore-microtubule attachments. By contrast, CENP-L depletion has no impact
      on mitotic progression in cells that have already separated their centrosomes at
      nuclear envelope breakdown. We propose that the kinetochore pushing force is an
      essential safety mechanism that favors amphitelic attachments by ensuring that
      spindle bipolarization occurs before the formation of the majority of kinetochore
      microtubule attachments.

PMID- 22399804
TI  - The microtubule poison vinorelbine kills cells independently of mitotic arrest
      and targets cells lacking the APC tumour suppressor more effectively.
AB  - Colorectal cancers commonly carry truncation mutations in the adenomatous
      polyposis coli (APC) gene. The APC protein contributes to the stabilization of
      microtubules. Consistently, microtubules in cells lacking APC depolymerize more
      readily in response to microtubule-destabilizing drugs. This raises the
      possibility that such agents are suitable for treatment of APC-deficient cancers.
      However, APC-deficient cells have a compromised spindle assembly checkpoint,
      which renders them less sensitive to killing by microtubule poisons whose
      toxicity relies on the induction of prolonged mitotic arrest. Here, we describe
      the novel discovery that the clinically used microtubule-depolymerizing drug
      vinorelbine (Navelbine) kills APC-deficient cells in culture and in intestinal
      tissue more effectively than it kills wild-type cells. This is due to the ability
      of vinorelbine to kill cells in interphase independently of mitotic arrest.
      Consistent with a role for p53 in cell death in interphase, depletion of p53
      renders cells less sensitive to vinorelbine, but only in the presence of wild
      type APC. The pro-apoptotic protein BIM (also known as BCL2L11) is recruited to
      mitochondria in response to vinorelbine, where it can inhibit the anti-apoptotic
      protein BCL2, suggesting that BIM mediates vinorelbine-induced cell death. This
      recruitment of BIM is enhanced in cells lacking APC. Consistently, BIM depletion
      dampens the selective effect of vinorelbine on these cells. Our findings reveal
      that vinorelbine is a potential therapeutic agent for colorectal cancer, but they
      also illustrate the importance of the APC tumour suppressor status when
      predicting therapeutic efficacy.

PMID- 22399805
TI  - Mitogen-activated protein kinase (MAPK/ERK) regulates adenomatous polyposis coli
      during growth-factor-induced cell extension.
AB  - Regulation of the microtubule- and actin-binding protein adenomatous polyposis
      coli (APC) is crucial for the formation of cell extensions in many cell types.
      This process requires inhibition of glycogen synthase kinase-3beta (GSK-3beta),
      which otherwise phosphorylates APC and decreases APC-mediated microtubule
      bundling. Although it is assumed, therefore, that APC phosphorylation is
      decreased during initiation of cell extensions, the phosphorylation state of APC
      has never been analyzed directly. We show here that NGF- and EGF-induced initial
      cell extensions result in APC phosphorylation by the MAPK/ERK pathway, which, in
      parallel with inhibition of GSK-3beta, promotes localization of APC to the tip of
      cell extensions. Whereas GSK-3beta inhibition promotes APC binding and
      stabilization of microtubules, we show that phosphorylation by ERK inhibits the
      interaction of APC with F-actin, and APC-mediated F-actin bundling, but not APC
      mediated microtubule bundling, in vitro. These results identify a previously
      unknown APC regulatory pathway during growth-factor-induced cell extension, and
      indicate that the GSK-3beta and ERK pathways act in parallel to regulate
      interactions between APC and the cytoskeleton during the formation of cell
      extensions.

PMID- 22399806
TI  - A motif of eleven amino acids is a structural adaptation that facilitates motor
      capability of eutherian prestin.
AB  - Cochlear outer hair cells (OHCs) alter their length in response to transmembrane
      voltage changes. This so-called electromotility is the result of conformational
      changes of membrane-bound prestin. Prestin-based OHC motility is thought to be
      responsible for cochlear amplification, which contributes to the exquisite
      frequency selectivity and sensitivity of mammalian hearing. Prestin belongs to an
      anion transporter family, the solute carrier protein 26A (SLC26A). Prestin is
      unique in this family in that it functions as a voltage-dependent motor protein
      manifested by two hallmarks, nonlinear capacitance and motility. Evidence
      suggests that prestin orthologs from zebrafish and chicken are anion exchangers
      or transporters with no motor function. We identified a segment of 11 amino acid
      residues in eutherian prestin that is extremely conserved among eutherian species
      but highly variable among non-mammalian orthologs and SLC26A paralogs. To
      determine whether this sequence represents a motif that facilitates motor
      function in eutherian prestin, we utilized a chimeric approach by swapping
      corresponding residues from the zebrafish and chicken with those of gerbil.
      Motility and nonlinear capacitance were measured from chimeric prestin
      transfected human embryonic kidney 293 cells using a voltage-clamp technique and
      photodiode-based displacement measurement system. We observed a gain of motor
      function with both of the hallmarks in the chimeric prestin without loss of
      transport function. Our results show, for the first time, that the substitution
      of a span of 11 amino acid residues confers the electrogenic anion transporters
      of zebrafish and chicken prestins with motor-like function. Thus, this motif
      represents the structural adaptation that assists gain of motor function in
      eutherian prestin.

PMID- 22399807
TI  - Syntenin, a syndecan adaptor and an Arf6 phosphatidylinositol 4,5-bisphosphate
      effector, is essential for epiboly and gastrulation cell movements in zebrafish.
AB  - Epiboly, the spreading and the thinning of the blastoderm to cover the yolk cell
      and close the blastopore in fish embryos, is central to the process of
      gastrulation. Despite its fundamental importance, little is known about the
      molecular mechanisms that control this coordinated cell movement. By a
      combination of knockdown studies and rescue experiments in zebrafish (Danio
      rerio), we show that epiboly relies on the molecular networking of syntenin with
      syndecan heparan sulphate proteoglycans, which act as co-receptors for adhesion
      molecules and growth factors. Furthermore, we show that the interaction of
      syntenin with phosphatidylinositol 4,5-bisphosphate (PIP2) and with the small
      GTPase ADP-ribosylation factor 6 (Arf6), which regulate the endocytic recycling
      of syndecan, is necessary for epiboly progression. Analysis of the earliest
      cellular defects suggests a role for syntenin in the autonomous vegetal expansion
      of the yolk syncytial layer and the rearrangement of the actin cytoskeleton in
      extra-embryonic tissues, but not in embryonic cell fate determination. This study
      identifies the importance of the syntenin-syndecan-PIP2-Arf6 complex for the
      progression of fish epiboly and establishes its key role in directional cell
      movements during early development.

PMID- 22399808
TI  - The HIF1 target gene NOX2 promotes angiogenesis through urotensin-II.
AB  - Urotensin-II (U-II) has been considered as one of the most potent vasoactive
      peptides, although its physiological and pathophysiological role is still not
      finally resolved. Recent evidence suggests that it promotes angiogenic responses
      in endothelial cells, although the underlying signalling mechanisms are unclear.
      Reactive oxygen species derived from NADPH oxidases are major signalling
      molecules in the vasculature. Because NOX2 is functional in endothelial cells, we
      investigated the role of the NOX2-containing NADPH oxidase in U-II-induced
      angiogenesis and elucidated a possible contribution of hypoxia-inducible factor-1
      (HIF-1), the master regulator of hypoxic angiogenesis, in the response to U-II.
      We found that U-II increases angiogenesis in vitro and in vivo, and these
      responses were prevented by antioxidants, NOX2 knockdown and in Nox2(-/-) mice.
      In addition, U-II-induced angiogenesis was dependent on HIF-1. Interestingly, U
      II increased NOX2 transcription involving HIF-1, and chromatin
      immunoprecipitation confirmed NOX2 as a target gene of HIF-1. In support, NOX2
      levels were greatly diminished in U-II-stimulated isolated vessels derived from
      mice deficient in endothelial HIF-1. Conversely, reactive oxygen species derived
      from NOX2 were required for U-II activation of HIF and upregulation of HIF-1. In
      line with this, U-II-induced upregulation of HIF-1 was absent in Nox2(-/-)
      vessels. Collectively, these findings identified HIF-1 and NOX2 as partners
      acting in concert to promote angiogenesis in response to U-II. Because U-II has
      been found to be elevated in cardiovascular disorders and in tumour tissues, this
      feed-forward mechanism could be an interesting anti-angiogenic therapeutic option
      in these disorders.

PMID- 22399809
TI  - Adenylyl cyclase AC8 directly controls its micro-environment by recruiting the
      actin cytoskeleton in a cholesterol-rich milieu.
AB  - The central and pervasive influence of cAMP on cellular functions underscores the
      value of stringent control of the organization of adenylyl cyclases (ACs) in the
      plasma membrane. Biochemical data suggest that ACs reside in membrane rafts and
      could compartmentalize intermediary scaffolding proteins and associated
      regulatory elements. However, little is known about the organization or
      regulation of the dynamic behaviour of ACs in a cellular context. The present
      study examines these issues, using confocal image analysis of various AC8
      constructs, combined with fluorescence recovery after photobleaching and
      fluorescence correlation spectroscopy. These studies reveal that AC8, through its
      N-terminus, enhances the cortical actin signal at the plasma membrane; an
      interaction that was confirmed by GST pull-down and immunoprecipitation
      experiments. AC8 also associates dynamically with lipid rafts; the direct
      association of AC8 with sterols was confirmed in Forster resonance energy
      transfer experiments. Disruption of the actin cytoskeleton and lipid rafts
      indicates that AC8 tracks along the cytoskeleton in a cholesterol-enriched
      domain, and the cAMP that it produces contributes to sculpting the actin
      cytoskeleton. Thus, an adenylyl cyclase is shown not just to act as a scaffold,
      but also to actively orchestrate its own micro-environment, by associating with
      the cytoskeleton and controlling the association by producing cAMP, to yield a
      highly organized signalling hub.

PMID- 22399810
TI  - Rad9B responds to nucleolar stress through ATR and JNK signalling, and delays the
      G1-S transition.
AB  - The complex formed by Rad9, Rad1 and Hus1 (9-1-1) protects against genomic
      instability by activating DNA damage checkpoint and DNA damage repair pathways,
      mainly in response to replication fork collapse and UV lesions. Here we compare
      the role of Rad9A (also known as Rad9) with the human paralogue Rad9B. Unlike
      Rad9A, overexpression of Rad9B delays cells in G1 phase. Moreover, Rad9B migrates
      to nucleoli after nucleolar stress in an ATR- and JNK-dependent manner, in a
      newly described nucleolar domain structure containing p21. Analysis of chimeras
      of Rad9A and Rad9B demonstrate that localisation to nucleoli and the block in G1
      phase upon overexpression crucially depend on the Rad9B C-terminal tail. Taken
      together, data presented here show a relationship between Rad9B and pathways for
      checkpoints, stress response and nucleolar function.

PMID- 22399811
TI  - Role of shear-stress-induced VEGF expression in endothelial cell survival.
AB  - Vascular endothelial growth factor (VEGF) plays a crucial role in developmental
      and pathological angiogenesis. Expression of VEGF in quiescent adult tissue
      suggests a potential role in the maintenance of mature blood vessels. We
      demonstrate, using a Vegf-lacZ reporter mouse model, that VEGF is expressed by
      arterial but not by venous or capillary endothelial cells (ECs) in vivo. Using an
      in vitro model, we show that arterial shear stress of human umbilical vein ECs
      (HUVECs) decreases apoptosis and increases VEGF expression, which is mediated by
      the induction of Kruppel-like factor 2 (KLF2). Additionally, shear stress
      stimulates the expression of VEGF receptor 2 (VEGFR2) and is associated with its
      activation. Knockdown of VEGF in shear stressed HUVECs blocks the protective
      effect of shear stress, resulting in EC apoptosis equivalent to that in control
      ECs cultured under static conditions. Similarly, treatment of ECs subjected to
      arterial shear stress with the VEGF receptor tyrosine kinase inhibitor SU1498, or
      VEGFR2 neutralizing antiserum, led to increased apoptosis, demonstrating that the
      mechanoprotection from increased shear is mediated by VEGFR2. Taken together,
      these studies suggest that arterial flow induces VEGF-VEGFR2 autocrine-juxtacrine
      signaling, which is a previously unidentified mechanism for vascular EC survival
      in adult arterial blood vessels.

PMID- 22399812
TI  - TGF-beta-induced activation of mTOR complex 2 drives epithelial-mesenchymal
      transition and cell invasion.
AB  - In cancer progression, carcinoma cells gain invasive behavior through a loss of
      epithelial characteristics and acquisition of mesenchymal properties, a process
      that can lead to epithelial-mesenchymal transition (EMT). TGF-beta is a potent
      inducer of EMT, and increased TGF-beta signaling in cancer cells is thought to
      drive cancer-associated EMT. Here, we examine the physiological requirement for
      mTOR complex 2 (mTORC2) in cells undergoing EMT. TGF-beta rapidly induces mTORC2
      kinase activity in cells undergoing EMT, and controls epithelial cell progression
      through EMT. By regulating EMT-associated cytoskeletal changes and gene
      expression, mTORC2 is required for cell migration and invasion. Furthermore,
      inactivation of mTORC2 prevents cancer cell dissemination in vivo. Our results
      suggest that the mTORC2 pathway is an essential downstream branch of TGF-beta
      signaling, and represents a responsive target to inhibit EMT and prevent cancer
      cell invasion and metastasis.

PMID- 22399813
TI  - Urinary vanin-1 as a novel biomarker for early detection of drug-induced acute
      kidney injury.
AB  - Drug-induced nephrotoxicity is a serious problem in patients with hospital
      acquired acute kidney injury (AKI). A new renal biomarker is needed because
      traditional markers are not sensitive for early detection of drug-induced AKI. In
      a recent study, we demonstrated that vanin-1 is a novel candidate biomarker of
      nephrotoxicant-induced kidney injury. The objective of the present study is to
      determine whether the increase in urinary vanin-1 is detected before the
      elevations of serum creatinine or urinary N-acetyl-beta-glucosaminidase (NAG),
      kidney injury molecule-1 (Kim-1), and neutrophil gelatinase-associated lipocalin
      (NGAL) in the two well established animal models of drug-induced AKI. After the
      administration of a higher dose of cisplatin (10 mg/kg, a single intraperitoneal
      dose) or gentamicin (120 mg/kg per day, once daily intraperitoneal dose for 9
      days), urinary vanin-1 was detected earlier than the other biomarkers. In rats
      treated with a lower dose of cisplatin (5 mg/kg, a single intraperitoneal dose)
      or gentamicin (40 mg/kg per day, once daily intraperitoneal dose for 9 days),
      serum creatinine and urinary NAG were not changed throughout the study period,
      whereas urinary vanin-1, Kim-1, and NGAL were significantly increased. The renal
      vanin-1 protein levels were significantly decreased in rats treated with the
      higher dose of cisplatin on day 5 and gentamicin on day 9, and the
      immunofluorescence analyses confirmed that vanin-1 immunoreactivity in tubular
      cells was reduced with the time after the dose of cisplatin, indicating that
      urinary vanin-1 was leaked from tubular cells. These results suggest that,
      compared with urinary Kim-1 and NGAL, urinary vanin-1 is an earlier and equally
      sensitive biomarker for drug-induced AKI.

PMID- 22399814
TI  - Compromising sigma-1 receptors at the endoplasmic reticulum render cytotoxicity
      to physiologically relevant concentrations of dopamine in a nuclear factor
      kappaB/Bcl-2-dependent mechanism: potential relevance to Parkinson's disease.
AB  - The endoplasmic reticulum (ER) chaperone sigma-1 receptor (Sig-1R) is
      cytoprotective against ER stress-induced apoptosis. The level of Sig-1Rs in the
      brain was reported to be lower in early parkinsonian patients. Because dopamine
      (DA) toxicity is well known to be involved in the etiology of Parkinson's
      disease, we tested in this study whether a relationship might exist between Sig
      1Rs and DA-induced cytotoxicity in a cellular model by using Chinese hamster
      ovary (CHO) cells. DA in physiological concentrations (e.g., lower than 10 MUM)
      does not cause apoptosis. However, the same concentrations of DA cause apoptosis
      in Sig-1R knockdown CHO cells. In search of a mechanistic explanation, we found
      that unfolded protein response is not involved. Rather, the level of protective
      protein Bcl-2 is critically involved in this DA/Sig-1R knockdown-induced
      apoptosis. Specifically, the DA/Sig-1R knockdown causes a synergistic proteasomal
      conversion of nuclear factor kappaB (NF-kappaB) p105 to the active form of p50,
      which is known to down-regulate the transcription of Bcl-2. It is noteworthy that
      the DA/Sig-1R knockdown-induced apoptosis is blocked by the overexpression of Bcl
      2. Our results therefore indicate that DA is involved in the activation of NF
      kappaB and suggest that endogenous Sig-1Rs are tonically inhibiting the
      proteasomal conversion/activation of NF-kappaB caused by physiologically relevant
      concentrations of DA that would otherwise cause apoptosis. Thus, Sig-1Rs and
      associated ligands may represent new therapeutic targets for the treatment of
      parkinsonism.

PMID- 22399815
TI  - When filling the glass only leaves it half empty! - insight into the
      cardiovascular physiology of haemorrhage under heat stress.

PMID- 22399816
TI  - Food for thought.

PMID- 22399817
TI  - Diet and gastric neurons.

PMID- 22399818
TI  - PTEN: a new player controlling structural and functional synaptic plasticity.

PMID- 22399819
TI  - The double hit of growth restriction: its origins and outcome on this generation
      and the next.

PMID- 22399820
TI  - Timing of inter-generational prevention of adiposity and type 2 diabetes.

PMID- 22399821
TI  - London 2012: the biomedical basis of elite performance.

PMID- 22399822
TI  - The analysis of human gastric pacemaker activity.

PMID- 22399824
TI  - N-Heterocyclic Carbene-Promoted Rauhut]Currier Reactions between Vinyl Sulfones
      and alpha,beta-Unsaturated Aldehydes.
AB  - N-heterocyclic carbenes (NHCs) promote the addition of 1,1
      bis(phenylsulfonyl)ethylene to the alpha-position of alpha,beta-unsaturated
      aldehydes. The proposed reaction pathway for this Rauhut-Currier-type reaction
      includes an unusual conjugate addition of an NHC to a bis-vinyl sulfone.

PMID- 22399825
TI  - Demographic Trends in the United States: A Review of Research in the 2000s.
AB  - Demographic trends in the 2000s showed the continuing separation of family and
      household due to factors such as childbearing among single parents, the
      dissolution of cohabiting unions, divorce, repartnering, and remarriage. The
      transnational families of many immigrants also displayed this separation, as
      families extended across borders. In addition, demographers demonstrated during
      the decade that trends such as marriage and divorce were diverging according to
      education. Moreover, demographic trends in the age structure of the population
      showed that a large increase in the elderly population will occur in the 2010s.
      Overall, demographic trends produced an increased complexity of family life and a
      more ambiguous and fluid set of categories than demographers are accustomed to
      measuring.

PMID- 22399826
TI  - The Use of Propensity Scores in Mediation Analysis.
AB  - Mediation analysis uses measures of hypothesized mediating variables to test
      theory for how a treatment achieves effects on outcomes and to improve subsequent
      treatments by identifying the most efficient treatment components. Most current
      mediation analysis methods rely on untested distributional and functional form
      assumptions for valid conclusions, especially regarding the relation between the
      mediator and outcome variables. Propensity score methods offer an alternative
      whereby the propensity score is used to compare individuals in the treatment and
      control groups who would have had the same value of the mediator had they been
      assigned to the same treatment condition. This article describes the use of
      propensity score weighting for mediation with a focus on explicating the
      underlying assumptions. Propensity scores have the potential to offer an
      alternative estimation procedure for mediation analysis with alternative
      assumptions from those of standard mediation analysis. The methods are
      illustrated investigating the mediational effects of an intervention to improve
      sense of mastery to reduce depression using data from the Job Search Intervention
      Study (JOBS II). We find significant treatment effects for those individuals who
      would have improved sense of mastery when in the treatment condition but no
      effects for those who would not have improved sense of mastery under treatment.

PMID- 22399831
TI  - The Relationship of Social Support to African American Caregivers' Help-Seeking
      for Emotional Problems.
AB  - This study analyzes whether social support serves as a link to or substitute for
      formal services among African American female caregivers seeking help with
      emotional problems. It also analyzes other determinants of help-seeking. It
      relies on data from the Black Rural and Urban Caregivers Mental Health and
      Functioning Study and is guided by a modified version of the behavioral model of
      health services use. Using hierarchical binary logistic regression, analyses
      reveal that only age, stress, and support from fellow church members are
      statistically significantly associated with the likelihood of help-seeking. These
      results support the linking hypothesis, suggesting that the social support
      received by African American women caregivers in the context of their religious
      organizations helps to link them to services.

PMID- 22399832
TI  - Measuring the lexical semantics of picture description in aphasia.
AB  - BACKGROUND: Individuals with non-fluent aphasia have difficulty producing
      syntactically laden words, such as function words, whereas individuals with
      fluent aphasia often have difficulty producing semantically specific words. It is
      hypothesised that such dissociations arise, at least in part, from a trade-off
      between syntactic and semantic sources of input to lexical retrieval.  AIMS: The
      aims of this study were (a) to identify quantitative measures of the semantic
      content of narrative for people with aphasia that are reliable indicators of
      semantic competence, independent of overall aphasia severity; (b) to determine
      whether these measures distinguish between fluent and non-fluent aphasia; and (c)
      to assess whether individuals with fluent and non-fluent aphasia show a trade-off
      between measures of syntactic and semantic production.  METHODS
      #ENTITYSTARTX00026; PROCEDURES: Connected speech samples were elicited from 16
      participants with aphasia, 8 fluent and 8 non-fluent. The semantic sufficiency of
      the samples was analysed by measuring the proportion of correct information units
      (CIUs), the type-token ratios (TTRs) of content words, and the proportion of
      semantically specific ("heavy") to semantically general ("light") verbs produced.
      These measures were then correlated with syntactic measures from the QPA (Berndt,
      Wayland, Rochon, Saffran, & Schwartz, 2000) across and within participant groups.
      OUTCOMES #ENTITYSTARTX00026; RESULTS: CIUs were found to reflect primarily
      aphasia severity, and not to differentiate between fluent and non-fluent groups.
      TTRs were also strongly influenced by severity among fluent, but not non-fluent,
      participants. The ratio of heavy to light verbs reliably distinguished the
      groups, and showed different patterns of correlation with the syntactic measures.
      CONCLUSIONS: Results show some evidence for a trade-off between syntactic and
      semantic inputs to word retrieval, at least among non-fluent participants. The
      heavy-light verb ratio provides information about semantic specificity, beyond
      what is provided by the CIU or TTR measures.

PMID- 22399833
TI  - Word learning: An ERP investigation of word experience effects on recognition and
      word processing.
AB  - Adults of varying reading comprehension skill learned a set of previously unknown
      rare English words (e.g., gloaming) in three different learning conditions in
      which the type of word knowledge was manipulated. The words were presented in one
      of three conditions: (1) orthography-to-meaning (no phonology); (2) orthography
      to-phonology (no meaning); and (3) phonology-to-meaning (no orthography).
      Following learning, participants made meaning judgments on the learned words,
      familiar known words, and unpresented (unlearned) rare words while their ERPs
      were recorded. The behavioral results showed no significant effects of
      comprehension skill on meaning judgment performance. Contrastingly, the ERP
      results indicated comprehension skill differences in P600 amplitude; high-skilled
      readers showed stronger familiarity effects for learned words, whereas less
      skilled readers did not distinguish between learned words, familiar words, and
      unlearned words. Evidence from the P600 and N400 illustrated superior learning of
      meaning when meaning information was coupled with orthography rather than
      phonology. These results suggest that the availability of word knowledge
      (orthography, phonology, and meaning) at learning affects subsequent word
      identification processes when the words are encountered in a new context.

PMID- 22399834
TI  - Near-infrared signals associated with electrical stimulation of peripheral
      nerves.
AB  - We report our studies on the optical signals measured non-invasively on
      electrically stimulated peripheral nerves. The stimulation consists of the
      delivery of 0.1 ms current pulses, below the threshold for triggering any visible
      motion, to a peripheral nerve in human subjects (we have studied the sural nerve
      and the median nerve). In response to electrical stimulation, we observe an
      optical signal that peaks at about 100 ms post-stimulus, on a much longer time
      scale than the few milliseconds duration of the electrical response, or sensory
      nerve action potential (SNAP). While the 100 ms optical signal we measured is not
      a direct optical signature of neural activation, it is nevertheless indicative of
      a mediated response to neural activation. We argue that this may provide
      information useful for understanding the origin of the fast optical signal (also
      on a 100 ms time scale) that has been measured non-invasively in the brain in
      response to cerebral activation. Furthermore, the optical response to peripheral
      nerve activation may be developed into a diagnostic tool for peripheral
      neuropathies, as suggested by the delayed optical signals (average peak time: 230
      ms) measured in patients with diabetic neuropathy with respect to normal subjects
      (average peak time: 160 ms).

PMID- 22399835
TI  - Imaging early demineralization with PS-OCT.
AB  - New methods are needed for the nondestructive measurement of tooth
      demineralization and remineralization to monitor the progression of incipient
      caries lesions (tooth decay) for effective nonsurgical intervention and to
      evaluate the performance of anti-caries treatments such as chemical treatments or
      laser irradiation. Studies have shown that optical coherence tomography (OCT) has
      great potential to fulfill this role since it can be used to measure the depth
      and severity of early lesions with an axial resolution exceeding 10-MUm, it is
      easy to apply in vivo and it can be used to image the convoluted topography of
      tooth occlusal surfaces. In this paper we attempt to determine the earliest stage
      at which we can detect significant differences in lesion severity. Automated
      methods of analysis were used to measure the depth and severity of demineralized
      bovine enamel produced using a simulated caries model that emulates
      demineralization in the mouth. Significant differences in the depth and
      integrated reflectivity from the lesions were detected after only a few hours of
      demineralization. These results demonstrate that cross polarization OCT is
      ideally suited for the nondestructive assessment of early demineralization.

PMID- 22399836
TI  - Near infrared imaging of teeth at wavelengths between 1200 and 1600 nm.
AB  - Near-IR (NIR) imaging is a new technology that is currently being investigated
      for the detection and assessment of dental caries without the use of ionizing
      radiation. Several papers have been published on the use of transillumination and
      reflectance NIR imaging to detect early caries in enamel. The purpose of this
      study was to investigate alternative near infrared wavelengths besides 1300-nm in
      the range from 1200-1600-nm to determine the wavelengths that yield the highest
      contrast in both transmission and reflectance imaging modes. Artificial lesions
      were created on thirty tooth sections of varying thickness for transillumination
      imaging. NIR images at wavelengths from the visible to 1600-nm were also acquired
      for fifty-four whole teeth with occlusal lesions using a tungsten halogen lamp
      with several spectral filters and a Ge-enhanced CMOS image sensor. Cavity
      preparations were also cut into whole teeth and Z250 composite was used as a
      restorative material to determine the contrast between composite and enamel at
      NIR wavelengths. Slightly longer NIR wavelengths are likely to have better
      performance for the transillumination of occlusal caries lesions while 1300-nm
      appears best for the transillumination of proximal surfaces. Significantly higher
      performance was attained at wavelengths that have higher water absorption, namely
      1460-nm and wavelengths greater than 1500-nm and these wavelength regions are
      likely to be more effective for reflectance imaging. Wavelengths with higher
      water absorption also provided higher contrast of composite restorations.

PMID- 22399837
TI  - Polarization Resolved Near-IR Imaging of Sound and Carious Dental Enamel.
AB  - A thorough understanding of how polarized near-IR light is reflected from and
      transmitted through sound and carious dental hard tissues is important for the
      development of optical imaging devices. New optical imaging tools employing non
      ionizing radiation are needed for the detection and assessment of dental caries.
      In this investigation, an automated system was developed to collect images for
      the full 16-element Mueller Matrix. The polarized light was controlled by linear
      polarizers and liquid crystal retarders and the 36 images were acquired as the
      polarized near-IR light is reflected from the occlusal surface or transmitted
      through thin sections of extracted human whole teeth. Previous near-IR imaging
      studies suggest that polarization imaging can be exploited to obtain higher
      contrast images of early dental caries due to the rapid depolarization of
      incident polarized light by the highly scattering areas of decay. In this study,
      the reflectance from tooth occlusal surfaces with demineralization and
      transmitted light through tooth thin sections with caries lesions were
      investigated. Major differences in the Mueller matrix elements were observed in
      both sound and demineralized enamel. This study suggests that polarization
      resolved optical imaging could be exploited to obtain higher contrast images of
      dental decay.

PMID- 22399838
TI  - Improve the Strength of PLA/HA Composite Through the Use of Surface Initiated
      Polymerization and Phosphonic Acid Coupling Agent.
AB  - Bioresorbable composite made from degradable polymers, e.g., polylactide (PLA),
      and bioactive calcium phosphates, e.g., hydroxyapatite (HA), are clinically
      desirable for bone fixation, repair and tissue engineering because they do not
      need to be removed by surgery after the bone heals. However, preparation of
      PLA/HA composite from non-modified HA usually results in mechanical strength
      reductions due to a weak interface between PLA and HA. In this study, a calcium
      phosphate/phosphonate hybrid shell was developed to introduce a greater amount of
      reactive hydroxyl groups onto the HA particles. Then, PLA was successfully
      grafted on HA by surface-initiated polymerization through the non-ionic surface
      hydroxyl groups. Thermogravimetric analysis indiated that the amount of grafted
      PLA on HA can be up to 7 %, which is about 50 % greater than that from the
      literature. PLA grafted HA shows significantly different pH dependent zeta
      potential and particle size profiles from those of uncoated HA. By combining the
      phosphonic acid coupling agent and surface initiated polymerization, PLA could
      directly link to HA through covalent bond so that the interfacial interaction in
      the PLA/HA composite can be significantly improved. The diametral tensile
      strength of PLA/HA composite prepared from PLA-grafted HA was found to be over
      twice that of the composite prepared from the non-modified HA. Moreover, the
      tensile strength of the improved composite was 23 % higher than that of PLA
      alone. By varying additional variables, this approach has the potential to
      produce bioresorbable composites with improved mechanical properties that are in
      the range of natural bones, and can have wide applications for bone fixation and
      repair in load-bearing areas.

PMID- 22399839
TI  - Local Sparse Bump Hunting.
AB  - The search for structures in real datasets e.g. in the form of bumps, components,
      classes or clusters is important as these often reveal underlying phenomena
      leading to scientific discoveries. One of these tasks, known as bump hunting, is
      to locate domains of a multidimensional input space where the target function
      assumes local maxima without pre-specifying their total number. A number of
      related methods already exist, yet are challenged in the context of high
      dimensional data. We introduce a novel supervised and multivariate bump hunting
      strategy for exploring modes or classes of a target function of many continuous
      variables. This addresses the issues of correlation, interpretability, and high
      dimensionality (p ? n case), while making minimal assumptions. The method is
      based upon a divide and conquer strategy, combining a tree-based method, a
      dimension reduction technique, and the Patient Rule Induction Method (PRIM).
      Important to this task, we show how to estimate the PRIM meta-parameters. Using
      accuracy evaluation procedures such as cross-validation and ROC analysis, we show
      empirically how the method outperforms a naive PRIM as well as competitive non
      parametric supervised and unsupervised methods in the problem of class discovery.
      The method has practical application especially in the case of noisy high
      throughput data. It is applied to a class discovery problem in a colon cancer
      micro-array dataset aimed at identifying tumor subtypes in the metastatic stage.
      Supplemental Materials are available online.

PMID- 22399840
TI  - Promoting Self-Care Management among Persons with Serious Mental Illness and HIV.
AB  - People with a serious mental illness (SMI) along with HIV have complex health
      conditions. This population also has high rates of poverty, difficulty in
      sustaining regular housing, and limited supportive networks. Typically, the
      combination of psychotropic and HIV medication regimens is complicated, changes
      frequently, and requires coordination among multiple providers. Furthermore,
      fragmented and divided primary health care and mental health care systems present
      substantial barriers for these individuals and for the public health nurses who
      care for them. In this paper, we present "real world" case studies of individuals
      with SMI and HIV and the self-care management strategies used by nurses to
      address medication and treatment management, build interpersonal skills, and
      develop sustainable health networks. The case studies can be used for quality
      improvement discussions among practicing public health nurses and for instructing
      nursing students in a self-care management approach.

PMID- 22399841
TI  - Inferring the phylogeny of bovidae using mitochondrial DNA sequences: resolving
      power of individual genes relative to complete genomes.
AB  - Molecular techniques that assess biodiversity through the analysis of a small
      segment of mitochondrial genome have been getting wide attention for inferring
      the mammalian diversity. Due to their highly conserved nature, specific
      mitochondrial genes offer a promising tool for phylogenetic analysis. However,
      there is no established criteria for selecting the typical mitochondrial DNA
      (mtDNA) segments to achieve a greater resolving power. We therefore chose the
      family Bovidae as a model and compared the tree-topologies resulting from the
      commonly used and phylogenetically-informative genes including 16S rRNA, 12S
      rRNA, COI, Cyt b and D-loop with respect to complete mitochondrial genome. The
      tree topologies from the whole mitochondrial genome of 12 species were not
      identical albeit similar with those resulting from the five individual genes
      mentioned above. High bootstrap values were observed for mtDNA compared with that
      of any single gene. The average pair-wise sequence divergence using different
      genetic modes was found to be: D-loop (0.229) > Cyt b (0.159) > COI or complete
      mtDNA (0.143) > 12S rRNA (0.094) > 16S rRNA (0.091). The tree resulting from
      complete mtDNA clearly separated the 12 taxa of Bovidae into 3 major clusters,
      one cluster each for subfamily Cervinae and Bovinae and the third cluster
      comprised the distinctive clades of Caprinae and Antilopinae. However, jumping
      clades of Antilopinae were observed while using the individual genes. This study
      showed that Bison bison and Bos Taurus have very close phylogenetic relationship
      compared to Bubalus bubalis (Bovinae), irrespective of the method used. Our
      findings suggest that complete mtDNA genome provides most reliable understanding
      of complex phylogenetic relationships while the reliability of individual gene
      trees should be verified with high bootstrap support.

PMID- 22399842
TI  - Evaluation of tensile strength of tissue adhesives and sutures for clear corneal
      incisions using porcine and bovine eyes, with a novel standardized testing
      platform.
AB  - BACKGROUND: Tissue adhesives for ophthalmologic applications were proposed almost
      50 years ago, yet to date no adequate tissue glues have been identified that
      combine strong sealing properties with adequate safety and absence of
      postsurgical side effects. In recent years, cataract surgeries and Descemet's
      stripping with endothelial keratoplasty procedures have significantly increased
      the number of clear corneal incisions performed. One of the obstacles to
      discovery and development of novel tissue adhesives has been the result of
      nonstandardized testing of potential tissue glues. METHODS: We developed an
      instrument capable of controlling intraocular pressure in explanted porcine and
      bovine eyes in order to evaluate sealants, adhesives, and surgical closure
      methods used in ophthalmic surgery in a controlled, repeatable, and validated
      fashion. We herein developed and validated our instrument by testing the adhesive
      properties of cyanoacrylate glue in both porcine and bovine explant eyes.
      RESULTS: The instrument applied and maintained intraocular pressure through a
      broad range of physiological intraocular pressures. Cyanoacrylate-based glues
      showed significantly enhanced sealing properties of clear corneal incisions
      compared with sutured wounds. CONCLUSION: This study shows the feasibility of our
      instrument for reliable and standardized testing of tissue adhesive for
      ophthalmological surgery.

PMID- 22399843
TI  - Inferior conjunctival autografting for pterygium surgery: an alternative way of
      preserving the glaucoma filtration site in far western Nepal.
AB  - BACKGROUND: The purpose of this study was to evaluate the outcome of pterygium
      excision with inferior conjunctival autografting for primary pterygium. METHODS:
      This was a prospective noncomparative interventional case series study enrolling
      50 eyes of 50 patients with primary pterygium between November 1, 2010 and
      October 30, 2011. All patients underwent the standard surgical technique for
      pterygium excision with inferior conjunctival autografting. The sampling method
      was purposive. The study variables were complications of surgery and recurrence
      rates during a follow-up period of 6 months. RESULTS: The mean age of the
      patients was 43 +/- 7.97 (range 26-64) years. Grade 1 pterygium comprised 64%
      while grade 2 pterygium comprised 36% of cases. The mean size of pterygium was
      3.2 +/- 0.60 mm. Minor complications did occur, but only 4% required resuturing.
      Recurrence occurred in two eyes (4%) which we detected 3 months after surgery in
      both cases. We observed conjunctival scarring at the donor site in four eyes
      (8%); however, there was no symblepharon formation or restriction of upgaze.
      CONCLUSION: Inferior conjunctival autografting is an effective technique with a
      low recurrence rate. This is a useful technique when it is not possible or
      desirable to use the superior conjunctiva as a donor source. It is an especially
      good option for preserving the glaucoma filtration site for the future.

PMID- 22399844
TI  - Use of DNA microarray analysis in diagnosis of bacterial and fungal
      endophthalmitis.
AB  - BACKGROUND: To examine the utility of DNA microarray analysis for identifying
      causative microorganisms in endophthalmitis. METHODS: Thirteen samples of
      vitreous fluid (VF) were obtained from 13 patients during vitrectomy. Vitreous
      fluids from three patients with suspected endophthalmitis and ten controls
      without infection were subjected to testing for the presence of bacteria and
      fungi in culture tests, polymerase chain reaction (PCR) analysis, and DNA
      microarray analysis. RESULTS: No control sample was positive for bacteria or
      fungi in the culture test, PCR, or microarray analysis. Specimens from two
      patients (Cases 1 and 2) with suspected endophthalmitis were positive for
      bacteria in PCR, and a specimen from one patient (Case 3) was positive for fungi
      in PCR. Klebsiella pneumonia (Case 1), Streptococcus agalactiae (Case 2), and
      Candida parapsilosis (Case 3) in the PCR-positive specimens were identified by
      DNA microarray analysis within 24 hours. Culture results were also positive for
      K. pneumonia in Case 1, S. agalactiae in Case 2, and C. parapsilosis in Case 3,
      but required 3 to 4 days to obtain. CONCLUSIONS: Microarray analysis is
      complementary to routine cultures for identifying causative microorganisms and is
      likely to be a useful tool in patients with suspected endophthalmitis who require
      rapid diagnosis and early antibiotic treatment.

PMID- 22399845
TI  - The association between primary open-angle glaucoma and fall: an observational
      study.
AB  - PURPOSE: Falls are among the most serious public health concerns for the elderly.
      Information conveyed via the visual sense is relevant to postural balance and
      movement, and proper visual function is essential to avoid falls. Here we
      investigated the prevalence of injurious falls among patients with primary open
      angle glaucoma (POAG) who were more than 45 years old, compared with comparably
      aged healthy subjects. METHODS: This is a cross-sectional study. Consecutive
      patients who visited the Tanabe Eye Clinic, Yamanashi, Japan between January 1
      and March 30, 2009 were screened for eligibility by ophthalmic examination. A
      total of 117 control subjects (77 men, 40 women; aged 60.2 +/- 7.5 years) who
      were free of ocular disease and 101 POAG patients (58 men, 43 women; aged 62.3 +/
      8.7 years) were consecutively enrolled. Participants answered a questionnaire on
      injurious fall experience during the previous 10 years. The prevalence of
      injurious fall in subjects with POAG versus healthy controls was examined with
      Fisher's exact test. Adjusted odds ratios and 95% confidence intervals were
      estimated with logistic regression models for the subjects with POAG (factors:
      age, gender, mean deviation in the better eye or worse eye). RESULTS: The self
      reported prevalence of injurious fall was 0.9% (1/117) in the control group and
      6.9% (7/101) in the POAG group. The association between injurious fall and POAG
      was statistically significant (P = 0.026, Fisher's exact test). Within the POAG
      patients, the group reporting falls was significantly older and had a lower BMI,
      worse BCVA, and worse mean deviation in both the better and worse eye than the
      group reporting no falls. Worse mean deviation in the eye with the better visual
      field (odds ratios 0.75; 95% confidence intervals: 0.57 to 0.99; P = 0.036) was a
      significant risk factor for injurious falls in subjects with POAG. CONCLUSIONS:
      POAG was significantly associated with injurious falls.

PMID- 22399846
TI  - Visual performance in cataract patients with low levels of postoperative
      astigmatism: full correction versus spherical equivalent correction.
AB  - PURPOSE: To evaluate whether visual performance could be improved in pseudophakic
      subjects by correcting low levels of postoperative astigmatism. METHODS: An
      exploratory, noninterventional study was conducted using subjects who had been
      implanted with an aspheric intraocular lens and had 0.5-0.75 diopter
      postoperative astigmatism. Monocular visual performance using full correction was
      compared with visual performance using spherical equivalent correction. Testing
      consisted of high- and low-contrast visual acuity, contrast sensitivity, and
      reading acuity and speed using the Radner Reading Charts. RESULTS: Thirty-eight
      of 40 subjects completed testing. Visual acuities at three contrast levels (100%,
      25%, and 9%) were significantly better using full correction than when using
      spherical equivalent correction (all P < 0.001). For contrast sensitivity testing
      under photopic, mesopic, and mesopic with glare conditions, only one out of
      twelve outcomes demonstrated a significant improvement with full correction
      compared with spherical equivalent correction (at six cycles per degree under
      mesopic without glare conditions, P = 0.046). Mean reading speed was numerically
      faster with full correction across all print sizes, reaching statistical
      significance at logarithm of the reading acuity determination (logRAD) 0.2, 0.7,
      and 1.1 (P < 0.05). Statistically significant differences also favored full
      correction in logRAD score (P = 0.0376), corrected maximum reading speed (P <
      0.001), and logarithm of the minimum angle of resolution/logRAD ratio (P <
      0.001). CONCLUSIONS: In this study of pseudophakic subjects with low levels of
      postoperative astigmatism, full correction yielded significantly better reading
      performance and high- and low-contrast visual acuity than spherical equivalent
      correction, suggesting that cataractous patients may benefit from surgical
      correction of low levels of preoperative corneal astigmatism.

PMID- 22399848
TI  - Spillover adherence effects of fixed-dose combination HIV therapy.
AB  - The impact of fixed-dose combination (FDC) products on adherence to other, non
      fixed regimen components has not been examined. We compared adherence to a third
      antiretroviral (ART) component among patients receiving a nucleoside reverse
      transcriptase inhibitor (NRTI) backbone consisting of the FDC Epzicom((r)),
      GlaxoSmithKline Inc, Research Triangle Park, NC (abacavir sulfate 600 mg +
      lamivudine 300 mg; FDC group) versus NRTI combinations taken as two separate
      pills (NRTI Combo group) using data from a national sample of 30 health plans
      covering approximately 38 million lives from 1997 to 2005. Adherence was measured
      as the medication possession ratio (MPR). Multivariate logistic regression
      compared treatment groups based on the likelihood of achieving >=95% adherence,
      with sensitivity analyses using alternative thresholds. MPR was assessed as a
      continuous variable using multivariate linear regression. Covariates included
      age, gender, insurance payer type, year of study drug initiation, presence of
      mental health and substance abuse disorders, and third agent class. The study
      sample consisted of 650 FDC and 1947 NRTI Combo patients. Unadjusted mean
      adherence to the third agent was higher in the FDC group than the NRTI Combo
      group (0.92 vs 0.85; P < 0.0001). In regression analyses, FDC patients were 48%
      and 39% more likely to achieve 95% and 90% third agent adherence, respectively (P
      <= 0.03). None of the other MPR specifications achieved comparable results. Among
      managed care patients, use of an FDC appears to substantially improve adherence
      to a third regimen component and thus the likelihood of achieving the accepted
      standard for adherence to HIV therapy of 95%.

PMID- 22399849
TI  - Structural and functional insights on the Myosin superfamily.
AB  - The myosin superfamily is a versatile group of molecular motors involved in the
      transport of specific biomolecules, vesicles and organelles in eukaryotic cells.
      The processivity of myosins along an actin filament and transport of
      intracellular 'cargo' are achieved by generating physical force from chemical
      energy of ATP followed by appropriate conformational changes. The typical myosin
      has a head domain, which harbors an ATP binding site, an actin binding site, and
      a light-chain bound 'lever arm', followed often by a coiled coil domain and a
      cargo binding domain. Evolution of myosins started at the point of evolution of
      eukaryotes, S. cerevisiae being the simplest one known to contain these molecular
      motors. The coiled coil domain of the myosin classes II, V and VI in whole
      genomes of several model organisms display differences in the length and the
      strength of interactions at the coiled coil interface. Myosin II sequences have
      long-length coiled coil regions that are predicted to have a highly stable
      dimeric interface. These are interrupted, however, by regions that are predicted
      to be unstable, indicating possibilities of alternate conformations, associations
      to make thick filaments, and interactions with other molecules. Myosin V
      sequences retain intermittent regions of strong and weak interactions, whereas
      myosin VI sequences are relatively devoid of strong coiled coil motifs.
      Structural deviations at coiled coil regions could be important for carrying out
      normal biological function of these proteins.

PMID- 22399850
TI  - Computational design of targeted inhibitors of polo-like kinase 1 (plk1).
AB  - Computational design of small molecule putative inhibitors of Polo-like kinase 1
      (Plk1) is presented. Plk1, which regulates the cell cycle, is often over
      expressed in cancers. Down regulation of Plk1 has been shown to inhibit tumor
      progression. Most kinase inhibitors interact with the ATP binding site on Plk1,
      which is highly conserved. This makes the development of Plk1-specific inhibitors
      challenging, since different kinases have similar ATP sites. However, Plk1 also
      contains a unique region called the polo-box domain (PBD), which is absent from
      other kinases. In this study, the PBD site was used as a target for designed Plk1
      putative inhibitors. Common structural features of several experimentally known
      Plk1 ligands were first identified. The findings were used to design small
      molecules that specifically bonded Plk1. Drug likeness and possible toxicities of
      the molecules were investigated. Molecules with no implied toxicities and optimal
      drug likeness values were used for docking studies. Several molecules were
      identified that made stable complexes only with Plk1 and LYN kinases, but not
      with other kinases. One molecule was found to bind exclusively the PBD site of
      Plk1. Possible utilization of the designed molecules in drugs against cancers
      with over expressed Plk1 is discussed.

PMID- 22399851
TI  - Total lung capacity by plethysmography and high-resolution computed tomography in
      COPD.
AB  - AIM: To characterize and compare total lung capacity (TLC) measured by
      plethysmography with high-resolution computed tomography (HRCT), and to identify
      variables that predict the difference between the two modalities. METHODS: Fifty
      nine consecutive patients referred for the evaluation of COPD were
      retrospectively reviewed. Patients underwent full pulmonary function testing and
      HRCT within 3 months. TLC was obtained by plethysmography as per American
      Thoracic Society/European Respiratory Society standards and by HRCT using custom
      software on 0.75 and 5 mm thick contiguous slices performed at full inspiration
      (TLC). RESULTS: TLC measured by plethysmography correlated with TLC measured by
      inspiratory HRCT (r = 0.92, P < 0.01). TLC measured by plethysmography was larger
      than that determined by inspiratory HRCT in most patients (mean of 6.46 +/- 1.28
      L and 5.34 +/- 1.20 L respectively, P < 0.05). TLC measured by both
      plethysmography and HRCT correlated significantly with indices of airflow
      obstruction (forced expiratory volume in 1 second/forced vital capacity [FVC] and
      FVC%), static lung volumes (residual volume, percent predicted [RV%], total lung
      capacity, percent predicted [TLC%], functional residual capacity, percent
      predicted [FRC%], and inspiratory capacity, percent predicted), and percent
      emphysema. TLC by plethysmography and HRCT both demonstrated significant inverse
      correlations with diffusion impairment. The absolute difference between TLC
      measured by plethysmography and HRCT increased as RV%, TLC%, and FRC% increased.
      Gas trapping (RV% and FRC%) independently predicted the difference in TLC between
      plethysmography and HRCT. CONCLUSION: In COPD, TLC by plethysmography can be up
      to 2 L greater than inspiratory HRCT. Gas trapping independently predicts
      patients for whom TLC by plethysmography differs significantly from HRCT.

PMID- 22399852
TI  - Utility of serum procalcitonin values in patients with acute exacerbations of
      chronic obstructive pulmonary disease: a cautionary note.
AB  - BACKGROUND: Serum procalcitonin levels have been used as a biomarker of invasive
      bacterial infection and recently have been advocated to guide antibiotic therapy
      in patients with chronic obstructive pulmonary disease (COPD). However, rigorous
      studies correlating procalcitonin levels with microbiologic data are lacking.
      Acute exacerbations of COPD (AECOPD) have been linked to viral and bacterial
      infection as well as noninfectious causes. Therefore, we evaluated procalcitonin
      as a predictor of viral versus bacterial infection in patients hospitalized with
      AECOPD with and without evidence of pneumonia. METHODS: Adults hospitalized
      during the winter with symptoms consistent with AECOPD underwent extensive
      testing for viral, bacterial, and atypical pathogens. Serum procalcitonin levels
      were measured on day 1 (admission), day 2, and at one month. Clinical and
      laboratory features of subjects with viral and bacterial diagnoses were compared.
      RESULTS: In total, 224 subjects with COPD were admitted for 240 respiratory
      illnesses. Of these, 56 had pneumonia and 184 had AECOPD alone. A microbiologic
      diagnosis was made in 76 (56%) of 134 illnesses with reliable bacteriology (26
      viral infection, 29 bacterial infection, and 21 mixed viral bacterial infection).
      Mean procalcitonin levels were significantly higher in patients with pneumonia
      compared with AECOPD. However, discrimination between viral and bacterial
      infection using a 0.25 ng/mL threshold for bacterial infection in patients with
      AECOPD was poor. CONCLUSION: Procalcitonin is useful in COPD patients for
      alerting clinicians to invasive bacterial infections such as pneumonia but it
      does not distinguish bacterial from viral and noninfectious causes of AECOPD.

PMID- 22399853
TI  - NIHSS and acute complications after anterior and posterior circulation strokes.
AB  - BACKGROUND: The purpose of this study was to determine whether the National
      Institutes of Health Stroke Scale (NIHSS) score was associated with inhospital
      neurological and medical complications (NMC) in patients with posterior
      circulation infarction. METHODS: This retrospective study included all patients
      admitted to our stroke unit during a one-year period (n = 289). NMC included
      neurological deterioration (ie, worsening by 4 points or more of the NIHSS score
      during the hospital stay) and all other medical complications based on what was
      recorded in the patients' charts. RESULTS: Seventy-nine patients (27%)
      experienced NMC. In posterior circulation infarction patients (n = 90), patients
      with NMC had a higher baseline NIHSS score (10.9 versus 2.2, P = 0.004) and a
      baseline NIHSS score >2 (78% versus 36%, P = 0.003). In stepwise logistic
      regression, an NIHSS score >2 (odds ratio: 8.2; 95% confidence interval: 1.64
      41.0; P = 0.01) was associated with NMC. Similar results were observed for
      anterior circulation infarction patients but with a higher cutoff value for NIHSS
      score. CONCLUSION: In ischemic stroke patients, an increased baseline NIHSS score
      was associated with an increased risk of NMC. This association applied to
      anterior-circulation as well as posterior circulation stroke, although zero on
      the NIHSS for posterior circulation stroke does not mean the absence of NMC
      during hospitalization. The clinical significance of these findings requires
      further evaluation in larger prospective studies.

PMID- 22399854
TI  - Ruxolitinib for the treatment of myelofibrosis: its clinical potential.
AB  - Ruxolitinib is an orally bioavailable, selective Janus kinase (JAK) 1 and 2
      inhibitor approved for the treatment of myelofibrosis (MF), a bone marrow disease
      in which the JAK pathway is dysregulated, leading to impaired hematopoiesis and
      immune function. By inhibiting JAK1 and JAK2, ruxolitinib modulates cytokine
      stimulated intracellular signaling. In a phase II clinical trial in patients with
      MF, ruxolitinib recipients exhibited durable reductions in spleen size,
      reductions in circulating pro-inflammatory cytokines, improvements in physical
      activity, weight gain, and alleviation of symptoms (including constitutional
      symptoms) in patients with and without JAK2 mutation. These findings were
      confirmed by two phase III clinical MF studies, in which a greater proportion of
      ruxolitinib recipients achieved a spleen volume reduction of >=35% from baseline
      at week 24, compared with placebo in one study (41.9% versus 0.7%; P < 0.0001)
      and with best available therapy in the other (31.9% versus 0%; P < 0.0001).
      Alleviation of MF symptoms and improvements in quality of life were also
      significantly greater in ruxolitinib recipients. Overall survival of patients
      treated with ruxolitinib was significantly longer than of those receiving the
      placebo. Owing to risks of potentially serious adverse effects, eg,
      myelosuppression, ruxolitinib should be used under close physician supervision.
      Longer follow-up of the phase III MF studies is needed to reach firm conclusions
      regarding ruxolitinib's capacity to modify the natural disease course.

PMID- 22399856
TI  - Outcome of the HORIZONS-AMI trial: bivalirudin enhances long-term survival in
      patients with ST-elevation myocardial infarction undergoing angioplasty.
AB  - Cardiovascular disease is the leading cause of death in the US. For patients with
      ST-elevation myocardial infarction (STEMI), urgent reperfusion of the culprit
      arterial occlusion, often achieved via primary percutaneous coronary intervention
      (PCI), reduces post-MI mortality and other major adverse cardiovascular events
      (MACE). Adjunctive antithrombotic and antiplatelet therapies are used during PCI
      to reduce MACE rates. Currently, a variety of antithrombotic options are
      available for peri-procedural use. The most commonly used agents include
      unfractionated heparin or low molecular weight heparin +/- glycoprotein IIb/IIIa
      inhibitors (GPI). These agents reduce the rates of peri-procedural ischemic and
      thrombotic events, though these benefits come at the cost of an increase in
      bleeding complications. Bivalirudin is a direct thrombin inhibitor with a short
      half-life and linear pharmacokinetics, which results in predictable serum
      concentrations and anticoagulant effect. Bivalirudin has emerged as an
      efficacious and safe alternative to heparin plus GP IIb/IIIa inhibitors in both
      stable coronary artery disease and acute coronary syndrome patients. In the
      HORIZONS-AMI trial, monotherapy with bivalirudin was compared with the
      combination of heparin and a GPI in a large population of patients with STEMI who
      underwent primary PCI. Bivalirudin treatment was associated with improved event
      free survival at 30 days and reduced rates of major bleeding. Based on the
      results of the trial, the American College of Cardiology/American Heart
      Association and European Society of Cardiology guidelines have incorporated
      recommendations for bivalirudin use in the setting of STEMI. Recently, 3-year
      follow-up data from the HORIZONS-AMI cohort were published, demonstrating
      sustained benefits in patients treated with bivalirudin, including reduced rates
      of mortality, cardiovascular mortality, reinfarction, and major bleeding events.
      These results further support the use of bivalirudin in the setting of primary
      PCI for STEMI given that its benefits are maintained through long-term follow-up.

PMID- 22399857
TI  - Absorbable stent: focus on clinical applications and benefits.
AB  - Coronary stents have improved very significantly the immediate and long-term
      results of percutaneous coronary interventions. However, once the vessel has
      healed, the scaffolding function of the stent is no longer needed, and the
      presence of a permanent metallic prosthesis poses important disadvantages. This
      has led to the idea of creating new devices that are able to provide mechanical
      support for a determined period and then disappear from the vessel, allowing its
      natural healing and avoiding the risks associated with having a permanent
      metallic cage, such as stent thrombosis. Absorbable stents currently appear as
      one of the most promising fields in interventional cardiology. The present
      article will review the available clinical evidence regarding these devices at
      present and their future perspectives.

PMID- 22399855
TI  - Challenges for heart disease stem cell therapy.
AB  - Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The use
      of stem cells to improve recovery of the injured heart after myocardial
      infarction (MI) is an important emerging therapeutic strategy. However, recent
      reviews of clinical trials of stem cell therapy for MI and ischemic heart disease
      recovery report that less than half of the trials found only small improvements
      in cardiac function. In clinical trials, bone marrow, peripheral blood, or
      umbilical cord blood cells were used as the source of stem cells delivered by
      intracoronary infusion. Some trials administered only a stem cell mobilizing
      agent that recruits endogenous sources of stem cells. Important challenges to
      improve the effectiveness of stem cell therapy for CVD include: (1) improved
      identification, recruitment, and expansion of autologous stem cells; (2)
      identification of mobilizing and homing agents that increase recruitment; and (3)
      development of strategies to improve stem cell survival and engraftment of both
      endogenous and exogenous sources of stem cells. This review is an overview of
      stem cell therapy for CVD and discusses the challenges these three areas present
      for maximum optimization of the efficacy of stem cell therapy for heart disease,
      and new strategies in progress.

PMID- 22399859
TI  - Bootcamp during neoadjuvant chemotherapy for breast cancer: a randomized pilot
      trial.
AB  - INTRODUCTION: Exercise may improve cancer outcomes. Neoadjuvant chemotherapy (NC)
      for breast cancer provides a unique setting to evaluate intervention effects.
      Treatments leading to decreased post-neoadjuvant Ki-67 levels, smaller tumor
      size, and higher pathologic response are associated with improved survival and
      lower recurrence. This randomized, prospective pilot trial evaluates the
      feasibility of supervised exercise during NC for breast cancer. METHODS: Stage II
      III, ER positive, cancer patients with BMI > 25 receiving NC were randomized to
      standard NC with supervised bootcamp (NC + BC) or NC alone. Ki-67, C-peptide,
      BMI, and tumor size were measured before chemotherapy and at time of surgery.
      RESULTS: There were no initial differences between groups in regards to tumor
      size, C-peptide, BMI, and Ki-67. The NC + BC (n = 5) group had a lower mean BMI
      at the conclusion of NC compared with those (n = 5) in the NC group (28.0 versus
      35.8, P = 0.03). Final tumor size was 2.59 cm in the NC + BC group versus 3.16 cm
      for NC (P = 0.76) Mean Ki-67 for NC + BC was 7% versus 29% with NC (P = 0.14). C
      peptide (ng/mL) was equivalent between the two groups (4.55 NC + BC versus 4.74
      NC, P = 0.85). CONCLUSIONS: Adding a supervised exercise program to NC is
      feasible, decreases BMI, and may lead to lower Ki-67 levels and improved
      survival.

PMID- 22399858
TI  - Differential pharmacology and benefit/risk of azilsartan compared to other
      sartans.
AB  - Azilsartan, an angiotensin II type 1 (AT(1)) receptor blocker (ARB), was recently
      approved by regulatory authorities for treatment of hypertension and is the 8th
      ARB to join the clinical market. This article discusses the medical reasons for
      introducing a new AT(1) receptor blocker and reviews the experimental and
      clinical studies that have compared the functional properties of azilsartan to
      those of other ARBs. The main question addressed is: Does azilsartan have
      distinguishing features that should motivate choosing it over any of the other
      sartans for use in clinical practice? Based on studies conducted to date in
      hypertensive patients without serious comorbidities, azilsartan appears to be
      characterized by a superior ability to control 24-hour systolic blood pressure
      (BP) relative to other widely used ARBs including valsartan, olmesartan, and
      candesartan, and presumably others as well (eg, losartan). Compared to these
      other ARBs, azilsartan may increase the BP target control and response rate by an
      absolute value of 8%-10%. Greater antihypertensive effects of azilsartan might be
      due in part to its unusually potent and persistent ability to inhibit binding of
      angiotensin II to AT(1) receptors. Preclinical studies have indicated that
      azilsartan may also have potentially beneficial effects on cellular mechanisms of
      cardiometabolic disease and insulin sensitizing activity that could involve more
      than just blockade of AT(1) receptors and/or reduction in BP. However, the
      clinical relevance of these additional actions is unknown. Given that the general
      ability of antihypertensive drugs to protect against target organ damage is
      largely mediated by their ability to decrease BP, the enhanced antihypertensive
      effects of azilsartan should serve to justify clinical interest in this ARB
      relative to other molecules in the class that have a lower capacity to reduce BP.

PMID- 22399860
TI  - Integrative Analysis of Response to Tamoxifen Treatment in ER-Positive Breast
      Cancer Using GWAS Information and Transcription Profiling.
AB  - Variable response and resistance to tamoxifen treatment in breast cancer patients
      remains a major clinical problem. To determine whether genes and biological
      pathways containing SNPs associated with risk for breast cancer are dysregulated
      in response to tamoxifen treatment, we performed analysis combining information
      from 43 genome-wide association studies with gene expression data from 298 ER(+)
      breast cancer patients treated with tamoxifen and 125 ER(+) controls. We
      identified 95 genes which distinguished tamoxifen treated patients from controls.
      Additionally, we identified 54 genes which stratified tamoxifen treated patients
      into two distinct groups. We identified biological pathways containing SNPs
      associated with risk for breast cancer, which were dysregulated in response to
      tamoxifen treatment. Key pathways identified included the apoptosis, P53, NFkB,
      DNA repair and cell cycle pathways. Combining GWAS with transcription profiling
      provides a unified approach for associating GWAS findings with response to drug
      treatment and identification of potential drug targets.

PMID- 22399861
TI  - Anti-inflammatory effects of a topical preparation containing nicotinamide,
      retinol, and 7-dehydrocholesterol in patients with acne: a gene expression study.
AB  - PURPOSE: Acne vulgaris is a skin disorder of the sebaceous follicles, involving
      hyperkeratinization and perifollicular inflammation. Aberrant extracellular
      matrix remodeling due to matrix metalloproteinases (MMPs) has been associated
      with the presence of acne conditions. Given the complex pathophysiology of acne,
      novel topical therapies should include combination products that target multiple
      pathogenetic mechanisms. In this pilot study we investigated the changes in gene
      expression of extracellular MMPs, the tissue inhibitors of metalloproteinases,
      and proinflammatory molecules after 45 days of topical application of a
      combination product containing nicotinamide, retinol, and 7-dehydrocholesterol in
      16 patients with inflammatory acne on their back. MATERIALS AND METHODS: Skin
      biopsies were obtained before and after treatment for gene expression studies.
      RESULTS: Quantitative real-time polymerase chain reaction revealed a significant
      downregulation of MMP-1, MMP-2, MMP-9, MMP-14, interleukin-6, monocyte
      chemoattractant protein-1, and macrophage migration inhibitory factor. In
      contrast, the tissue inhibitors of metalloproteinases and transforming growth
      factor-beta1 were significantly upregulated. The gene expression findings
      correlated well with the clinical treatment response. CONCLUSIONS: The
      combination of nicotinamide, retinol, and 7-dehydrocholesterol appears to be
      effective for acne treatment from both clinical and molecular standpoints.

PMID- 22399862
TI  - Lingual angioedema with macroglossia during the treatment of acute ischemic
      stroke with alteplase.
AB  - Alteplase (recombinant tissue plasminogen activator) has been used in the
      treatment of acute ischemic stroke for 10 years. The application of this drug is
      considered safe and effective. However, alteplase is also associated with side
      effects. The author is reporting on an unusual side effect of angioedema that is
      triggered by alteplase. Angioedema occurs through alteplase according to this
      study at a frequency of 5.88% (95% confidence interval: 0.98% to 28.76%). In this
      case immunoglobulin G was slightly increased. The relative risk to get an
      angioedema compared between the two genders is elevated in men 3.3 (95%
      confidence interval: 0.15% to 71.90%; P = 0.4423), who were 3.3 times more likely
      to suffer than women. The use of angiotensin-converting-enzyme (ACE) inhibitors
      is considered a possible risk factor for the occurrence of angioedema with
      concomitant administration of tissue plasminogen activator. The angioedema may
      occur with use of alteplase at any time, so treatment with this drug must always
      be carried out in intensive care and doctors must be ready for intubation if
      necessary.

PMID- 22399863
TI  - Energy drinks mixed with alcohol: misconceptions, myths, and facts.
AB  - BACKGROUND: Whilst energy drinks improve performance and feelings of alertness,
      recent articles suggest that energy drink consumption combined with alcohol may
      reduce perception of alcohol intoxication, or lead to increased alcohol or drug
      use. This review discusses the available scientific evidence on the effects of
      mixing energy drinks with alcohol. METHODS: A literature search was performed
      using the keywords "energy drink and Red Bull((r))" and consulting
      Medline/Pubmed, PsycINFO, and Embase. RESULTS: There is little evidence that
      energy drinks antagonize the behavioral effects of alcohol, and there is no
      consistent evidence that energy drinks alter the perceived level of intoxication
      of people who mix energy drinks with alcohol. No clinically relevant
      cardiovascular or other adverse effects have been reported for healthy subjects
      combining energy drinks with alcohol, although there are no long-term
      investigations currently available. Finally, whilst several surveys have shown
      associations, there is no direct evidence that coadministration of energy drinks
      increases alcohol consumption, or initiates drug and alcohol dependence or abuse.
      CONCLUSION: Although some reports suggest that energy drinks lead to reduced
      awareness of intoxication and increased alcohol consumption, a review of the
      available literature shows that these views are not supported by direct or
      reliable scientific evidence. A personality with higher levels of risk-taking
      behavior may be the primary reason for increased alcohol and drug abuse per se.
      The coconsumption of energy drinks being one of the many expressions of that type
      of lifestyle and personality.

PMID- 22399865
TI  - Predicting prediabetes in a rural community: a survey among the Karen ethnic
      community, Thasongyang, Thailand.
AB  - BACKGROUND: Diabetes is a growing epidemic in both urban and rural communities
      worldwide. AIM: We aimed to survey fasting plasma glucose (FPG) status and
      awareness of diabetes in the rural Karen ethnic community. We investigated the
      predictors of impaired fasting plasma glucose (IFG) status, which would be easily
      applicable for prevention of diabetes in a rural community. MATERIALS AND
      METHODS: This was a community-based cross-sectional study conducted at
      Thasongyang, the most north-western district in Thailand. A total of 299 Karen
      ethnic rural residents were included in the study. FPG, body mass index, and
      waist circumference were prospectively measured. We assessed the awareness of
      diabetes and lifestyle-related health behavior with closed questionnaires in a
      rural community setting. RESULTS: On screening for FPG, 16.72% of the Karen
      ethnic residents had hyperglycemia: 3.68% in the diabetic range and 13.04% in the
      prediabetic range respectively. After adjustment for age, sex, and BMI, waist
      circumference (adjusted odds ratio [aOR] 3.5, 95% confidence interval [CI] 1.29
      9.57), and having a diabetic blood relative (aOR 4.6, CI 1.81-11.71) are
      significant predictors of IFG status. CONCLUSION: It is necessary to promote
      awareness of diabetes among the Karen ethnic community. Application of simple
      evidence-based predictors of the prediabetic state may lead to timely and
      effective prevention of diabetes in rural settings.

PMID- 22399866
TI  - Analysis on descriptions of precautionary statements in package inserts of
      medicines.
AB  - BACKGROUND: To prevent medical accidents, users must be informed of the cautions
      written in medical package inserts. To realize countermeasures by utilizing
      information systems, we must also implement a drug information database. However,
      this is not easy to develop, since the descriptions in package inserts are too
      complex and their information poorly structured. It is necessary to analyze
      package insert information and propose a data structure. METHODS: We analyzed the
      descriptions of 'precautions for application' in package inserts via text mining
      methods. In order to summarize statements, we applied dependency analysis to
      statements and visualized their relations between predicate words and other
      words. Furthermore, we extracted words representing timing to execute the order.
      RESULTS: WE FOUND THAT THERE ARE FOUR TYPES OF STATEMENTS: direct orders such as
      " " (use), causative orders such as " " (make someone use), direct interdictions
      such as " " (do not use), and causative interdictions such as " " (do not make
      user use). As for words representing timing, we extracted six groups: "at the
      time of delivery," "at the time of preparation," "in use," "after use," and "at
      the time of storage." From these results, we obtained points of consideration
      concerning the subjects of orders in the statements and timing of their
      execution. CONCLUSION: From the obtained knowledge, we can define the information
      structure used to describe the precautionary statement. It should contain
      information such as the actions described in the statement, the flag to express
      an order or interdiction, the subject to be ordered, and the timing.

PMID- 22399864
TI  - Prevalence and risk factors associated with nutrition-related noncommunicable
      diseases in the Eastern Mediterranean region.
AB  - This paper reviews the current situation concerning nutrition-related
      noncommunicable diseases (N-NCDs) and the risk factors associated with these
      diseases in the Eastern Mediterranean region (EMR). A systematic literature
      review of studies and reports published between January 1, 1990 and September 15,
      2011 was conducted using the PubMed and Google Scholar databases. Cardiovascular
      disease, type 2 diabetes, metabolic syndrome, obesity, cancer, and osteoporosis
      have become the main causes of morbidity and mortality, especially with
      progressive aging of the population. The estimated mortality rate due to
      cardiovascular disease and diabetes ranged from 179.8 to 765.2 per 100,000
      population, with the highest rates in poor countries. The prevalence of metabolic
      syndrome was very high, ranging from 19% to 45%. The prevalence of overweight and
      obesity (body mass index >=25 kg/m(2)) has reached an alarming level in most
      countries of the region, ranging from 25% to 82%, with a higher prevalence among
      women. The estimated mortality rate for cancer ranged from 61.9 to 151 per
      100,000 population. Osteoporosis has become a critical problem, particularly
      among women. Several risk factors may be contributing to the high prevalence of N
      NCDs in EMR, including nutrition transition, low intake of fruit and vegetables,
      demographic transition, urbanization, physical inactivity, hypertension, tobacco
      smoking, stunting of growth of preschool children, and lack of nutrition and
      health awareness. Intervention programs to prevent and control N-NCDs are
      urgently needed, with special focus on promotion of healthy eating and physical
      activity.

PMID- 22399867
TI  - Conservative management of skin fistula occurring after internal cardioverter
      defibrillator replacement.
AB  - Skin fistula occurring after cardiac electronic device implantation is frequently
      related to pocket infection and this condition typically requires removal of
      device and lead(s). We report on a case of skin fistula occurring 3 weeks after
      internal cardioverter defibrillator replacement. Conservative management
      consisted of local care along with oral antibiotics without removal of device;
      this strategy resulted in complete healing and closure of the fistula.

PMID- 22399868
TI  - Adalimumab monotherapy in a patient with psoriatic arthritis associated with
      chronic renal failure on hemodialysis: a case report and literature review.
AB  - We report a patient with psoriatic arthritis (PsA) who was successfully treated
      with adalimumab even while under hemodialysis therapy for associated chronic
      renal failure. Flow cytometry of circulating lymphocytes revealed an obvious
      decrease in both Th1 and Th17 cells after starting adalimumab. The latter
      returned to the pretreatment level in the course of adalimumab therapy, while the
      former did not. Adalimumab is a potent therapeutic option for PsA patients with
      chronic renal failure on hemodialysis, and Th1 in peripheral blood may reflect
      the disease activity.

PMID- 22399869
TI  - 14,000 volt electrical injury to bilateral upper extremities: a case report.
AB  - Electrical burns are among the most devastating of burn injuries. High voltage
      electrical injuries result in extensive deep tissue damage and are associated
      with multiple complications, long term morbidity, and a high mortality rate. We
      describe the case of a 47 year-old electric company linesman who suffered a high
      voltage electrical injury (HVEI) of 14,000 volts to bilateral hands and wrists
      managed by the Division of Plastic and Reconstructive Surgery at the McGill
      University Health Center in Montreal, Quebec, Canada. His management included
      multiple operative procedures, including escharotomies, fasciotomies, serial
      debridements, and bilateral pedicle groin flaps, and amputation of his left hand.

PMID- 22399870
TI  - ICA Occlusion by an ACTH-secreting pituitary adenoma post-TSS and irradiation.
AB  - Occlusion of intracranial arteries by a pituitary adenoma with ensuing infarction
      is a rare occurrence. In this case study, we show the instance of a pituitary
      macroadenoma and apoplexy causing mechanical obstruction of the internal carotid
      artery with consequent infarction following transphenoidal surgery (TSS) and
      radiation therapy in a patient with Cushing's disease. We report a 44-year-old
      woman presented with amenorrhea and headaches. Necessary investigations,
      resection by TSS, and microscopic examination revealed an adenocorticotropin
      (ACTH)-secreting pituitary macroadenoma. The pituitary tumour recurred in
      subsequent years, resulting in the development of Cushing's disease and syndrome.
      Despite two more transphenoidal surgeries, radiotherapy, and medical suppressive
      therapy, the pituitary adenoma continued to enlarge, and the hypercortisolemia
      and Cushingoid symptoms persisted. A craniotomy was arranged as the next step in
      the treatment strategy. Only hours prior to the scheduled surgery, the patient
      developed left-sided hemiplegia, was diagnosed with acute occlusion of the right
      ICA and underwent an emergency bifrontal craniotomy with evacuation of the tumour
      and decompression. Pathological examination revealed evidence of apoplexy in the
      ACTH-secreting pituitary adenoma. This case demonstrates the vast scope of
      complications that can arise from pituitary adenomas despite combination therapy
      and forewarns clinicians to be prepared to manage these infrequent but
      conceivable occurrences.

PMID- 22399871
TI  - Maternal hemoglobin concentration and pregnancy outcome: a study of the effects
      of elevation in el alto, bolivia.
AB  - Iron-deficiency anemia is often under-diagnosed in developing countries,
      specifically in pregnant populations in regions of high altitude. Hemoglobin
      levels are not consistently adjusted for elevation, and therefore many anemic
      patients are left undiagnosed. The purpose of this study was to incorporate
      current parameters for diagnosing anemia in pregnancy at high altitudes, and to
      evaluate the effects of appropriately adjusted hemoglobin concentrations on
      pregnancy outcome. A few studies have examined the effect of elevation on
      hemoglobin status, and other studies have considered the effects of anemia of
      pregnancy; however, there is a lack of data demonstrating that altitude-adjusted
      hemoglobin levels accurately predict pregnancy outcome. Using the Student t-Test,
      multiple linear regression, and ANOVA statistical analyses, various factors of
      pregnancy outcome were compared between anemic and non-anemic groups, as defined
      by hemoglobin cut-off levels adjusted for trimester of pregnancy and altitude.
      When appropriate adjustments were used, maternal anemia was associated with lower
      infant Apgar scores at both one minute and five minutes after birth, as well as
      complication of labor, lower gestational age at birth, and higher parity. This
      study demonstrates the importance of altitude and trimester specific adjustments
      to maternal hemoglobin levels in order to accurately diagnose anemia in
      pregnancy. In addition, a clear correlation is seen between maternal hemoglobin
      level and pregnancy outcome.

PMID- 22399872
TI  - Male physicians treating Female patients: Issues, Controversies and Gynecology.

PMID- 22399873
TI  - Ultrasound: from Earth to space.
AB  - Ultrasonography is a versatile imaging modality that offers many advantages over
      radiography, computed tomography, and magnetic resonance imaging. On Earth, the
      use of ultrasound has become standard in many areas of medicine including
      diagnosis of medical and surgical diseases, management of obstetric and
      gynecologic conditions, assessment of critically ill patients, and procedural
      guidance. Advances in telecommunications have enabled remotely-guided
      ultrasonography for both geographically isolated populations and astronauts
      aboard the International Space Station. While ultrasound has traditionally been
      used in spaceflight to study anatomical and physiological adaptations to
      microgravity and evaluate countermeasures, recent years have seen a growth of
      applications adapted from terrestrial techniques. Terrestrial, remote, and space
      applications for ultrasound are reviewed in this paper.

PMID- 22399875
TI  - CMOS-integrated film bulk acoustic resonators for label-free biosensing.
AB  - The throughput is an important parameter for label-free biosensors. Acoustic
      resonators like the quartz crystal microbalance have a low throughput because the
      number of sensors which can be used at the same time is limited. Here we present
      an array of 64 CMOS-integrated film bulk acoustic resonators. We compare the
      performance with surface plasmon resonance and the quartz crystal microbalance
      and demonstrate the performance of the sensor for multiplexed detection of DNA.

PMID- 22399876
TI  - Reliable fiber sensor system with star-ring-bus architecture.
AB  - This work presents a novel star-ring-bus sensor system and demonstrates its
      effectiveness. The main trunk of the proposed sensor system is a star topology
      and the sensing branches comprise a series of bus subnets. Any weakness in the
      reliability of the sensor system is overcome by adding remote nodes and switches
      to the ring and bus subnets. To construct the proposed star-ring-bus sensor
      system, a fiber ring laser scheme is used to improve the signal-to-noise ratio of
      the sensor system. The proposed system increases the reliability and capacity of
      fiber sensor systems.

PMID- 22399877
TI  - Generating one biometric feature from another: faces from fingerprints.
AB  - This study presents a new approach based on artificial neural networks for
      generating one biometric feature (faces) from another (only fingerprints). An
      automatic and intelligent system was designed and developed to analyze the
      relationships among fingerprints and faces and also to model and to improve the
      existence of the relationships. The new proposed system is the first study that
      generates all parts of the face including eyebrows, eyes, nose, mouth, ears and
      face border from only fingerprints. It is also unique and different from similar
      studies recently presented in the literature with some superior features. The
      parameter settings of the system were achieved with the help of Taguchi
      experimental design technique. The performance and accuracy of the system have
      been evaluated with 10-fold cross validation technique using qualitative
      evaluation metrics in addition to the expanded quantitative evaluation metrics.
      Consequently, the results were presented on the basis of the combination of these
      objective and subjective metrics for illustrating the qualitative properties of
      the proposed methods as well as a quantitative evaluation of their performances.
      Experimental results have shown that one biometric feature can be determined from
      another. These results have once more indicated that there is a strong
      relationship between fingerprints and faces.

PMID- 22399878
TI  - Development of a three dimensional neural sensing device by a stacking method.
AB  - This study reports a new stacking method for assembling a 3-D microprobe array.
      To date, 3-D array structures have usually been assembled with vertical spacers,
      snap fasteners and a supporting platform. Such methods have achieved 3-D
      structures but suffer from complex assembly steps, vertical interconnection for 3
      D signal transmission, low structure strength and large implantable opening. By
      applying the proposed stacking method, the previous techniques could be replaced
      by 2-D wire bonding. In this way, supporting platforms with slots and vertical
      spacers were no longer needed. Furthermore, ASIC chips can be substituted for the
      spacers in the stacked arrays to achieve system integration, design flexibility
      and volume usage efficiency. To avoid overflow of the adhesive fluid during
      assembly, an anti-overflow design which made use of capillary action force was
      applied in the stacking method as well. Moreover, presented stacking procedure
      consumes only 35 minutes in average for a 4 * 4 3-D microprobe array without
      requiring other specially made assembly tools. To summarize, the advantages of
      the proposed stacking method for 3-D array assembly include simplified assembly
      process, high structure strength, smaller opening area and integration ability
      with active circuits. This stacking assembly technique allows an alternative
      method to create 3-D structures from planar components.

PMID- 22399879
TI  - Real-time time-frequency two-dimensional imaging of ultrafast transient signals
      in solid-state organic materials.
AB  - In this review, we demonstrate a real-time time-frequency two-dimensional (2D)
      pump-probe imaging spectroscopy implemented on a single shot basis applicable to
      excited-state dynamics in solid-state organic and biological materials. Using
      this technique, we could successfully map ultrafast time-frequency 2D transient
      absorption signals of beta-carotene in solid films with wide temporal and
      spectral ranges having very short accumulation time of 20 ms per unit frame. The
      results obtained indicate the high potential of this technique as a powerful and
      unique spectroscopic tool to observe ultrafast excited-state dynamics of organic
      and biological materials in solid-state, which undergo rapid photodegradation.

PMID- 22399880
TI  - Monitoring of water content in building materials using a wireless passive
      sensor.
AB  - This paper describes an innovative design of a wireless, passive LC sensor and
      its application for monitoring of water content in building materials. The sensor
      was embedded in test material samples so that the internal water content of the
      samples could be measured with an antenna by tracking the changes in the sensor's
      resonant frequency. Since the dielectric constant of water was much higher
      compared with that of the test samples, the presence of water in the samples
      increased the capacitance of the LC circuit, thus decreasing the sensor's
      resonant frequency. The sensor is made up of a printed circuit board in one metal
      layer and water content has been determined for clay brick and autoclaved aerated
      concrete block, both widely used construction materials. Measurements were
      conducted at room temperature using a HP-4194A Impedance/Gain-Phase Analyzer
      instrument.

PMID- 22399881
TI  - A Geographic Information System framework for the management of sensor
      deployments.
AB  - A prototype Geographic Information System (GIS) framework has been developed to
      map, manage, and monitor sensors with respect to other geographic features,
      including land base and in-plant features. The GIS framework supports geographic
      placement and subsequent discovery, query, and tasking of sensors in a network
      centric environment using Web services. The framework couples the GIS feature
      placement logic of sensors with an extensible ontology which captures the
      capabilities, properties, protocols, integrity constraints, and other parameters
      of interest for a large variety of sensor types. The approach is significant in
      that custom, GIS-based interfaces can be rapidly developed via the integration of
      sensors and sensor networks into applications without having detailed knowledge
      of the sensors' underlying device drivers by leveraging service-oriented
      computing infrastructure within the GIS framework.

PMID- 22399882
TI  - Generation and amplification of tunable multicolored femtosecond laser pulses by
      using cascaded four-wave mixing in transparent bulk media.
AB  - We have reviewed the generation and amplification of wavelength-tunable
      multicolored femtosecond laser pulses using cascaded four-wave mixing (CFWM) in
      transparent bulk media, mainly concentrating on our recent work. Theoretical
      analysis and calculations based on the phase-matching condition could explain
      well the process semi-quantitatively. The experimental studies showed: (1) as
      many as fifteen spectral up-shifted and two spectral down-shifted sidebands were
      obtained simultaneously with spectral bandwidth broader than 1.8 octaves from
      near ultraviolet (360 nm) to near infrared (1.2 MUm); (2) the obtained sidebands
      were spatially separated well and had extremely high beam quality with M(2)
      factor better than 1.1; (3) the wavelengths of the generated multicolor sidebands
      could be conveniently tuned by changing the crossing angle or simply replacing
      with different media; (4) as short as 15-fs negatively chirped or nearly
      transform limited 20-fs multicolored femtosecond pulses were obtained when one of
      the two input beams was negatively chirped and the other was positively chirped;
      (5) the pulse energy of the sideband can reach a MUJ level with power stability
      better than 1% RMS; (6) broadband two-dimensional (2-D) multicolored arrays with
      more than ten periodic columns and more than ten rows were generated in a
      sapphire plate; (7) the obtained sidebands could be simultaneously spectra
      broadened and power amplified in another bulk medium by using cross-phase
      modulation (XPM) in conjunction with four-wave optical parametric amplification
      (FOPA). The characterization showed that this is interesting and the CFWM
      sidebands generated by this novel method have good enough qualities in terms of
      power stability, beam quality, and temporal features suited to various
      experiments such as ultrafast multicolor time-resolved spectroscopy and
      multicolor-excitation nonlinear microscopy.

PMID- 22399883
TI  - Ultrafast laser-based spectroscopy and sensing: applications in LIBS, CARS, and
      THz spectroscopy.
AB  - Ultrafast pulsed lasers find application in a range of spectroscopy and sensing
      techniques including laser induced breakdown spectroscopy (LIBS), coherent Raman
      spectroscopy, and terahertz (THz) spectroscopy. Whether based on absorption or
      emission processes, the characteristics of these techniques are heavily
      influenced by the use of ultrafast pulses in the signal generation process.
      Depending on the energy of the pulses used, the essential laser interaction
      process can primarily involve lattice vibrations, molecular rotations, or a
      combination of excited states produced by laser heating. While some of these
      techniques are currently confined to sensing at close ranges, others can be
      implemented for remote spectroscopic sensing owing principally to the laser pulse
      duration. We present a review of ultrafast laser-based spectroscopy techniques
      and discuss the use of these techniques to current and potential chemical and
      environmental sensing applications.

PMID- 22399884
TI  - Polarization dependence suppression of optical fiber grating sensor in a pi
      shifted Sagnac loop interferometer.
AB  - In the sensing applications of optical fiber grating, it is necessary to reduce
      the transmission-type polarization dependence to isolate the sensing parameter.
      It is experimentally shown that the polarization-dependent spectrum of acousto
      optic long-period fiber grating sensors can be suppressed in the transmission
      port of a pi-shifted Sagnac loop interferometer. General expressions for the
      transmittance and reflectance are derived for transmission-type, reflection-type,
      and partially reflecting/transmitting-type polarization-dependent optical
      devices. The compensation of polarization dependence through the counter
      propagation in the Sagnac loop interferometer is quantitatively measured for a
      commercial in-line polarizer and an acousto-optic long-period fiber grating
      sensor.

PMID- 22399886
TI  - Untraceable mobile node authentication in WSN.
AB  - Mobility of sensor node in Wireless Sensor Networks (WSN) brings security issues
      such as re-authentication and tracing the node movement. However, current
      security researches on WSN are insufficient to support such environments since
      their designs only considered the static environments. In this paper, we propose
      the efficient node authentication and key exchange protocol that reduces the
      overhead in node re-authentication and also provides untraceability of mobile
      nodes. Compared with previous protocols, our protocol has only a third of
      communication and computational overhead. We expect our protocol to be the
      efficient solution that increases the lifetime of sensor network.

PMID- 22399885
TI  - Responsive hydrogels for label-free signal transduction within biosensors.
AB  - Hydrogels have found wide application in biosensors due to their versatile
      nature. This family of materials is applied in biosensing either to increase the
      loading capacity compared to two-dimensional surfaces, or to support biospecific
      hydrogel swelling occurring subsequent to specific recognition of an analyte.
      This review focuses on various principles underpinning the design of biospecific
      hydrogels acting through various molecular mechanisms in transducing the
      recognition event of label-free analytes. Towards this end, we describe several
      promising hydrogel systems that when combined with the appropriate readout
      platform and quantitative approach could lead to future real-life applications.

PMID- 22399887
TI  - Measurement uncertainty estimation in amperometric sensors: a tutorial review.
AB  - This tutorial focuses on measurement uncertainty estimation in amperometric
      sensors (both for liquid and gas-phase measurements). The main uncertainty
      sources are reviewed and their contributions are discussed with relation to the
      principles of operation of the sensors, measurement conditions and properties of
      the measured samples. The discussion is illustrated by case studies based on the
      two major approaches for uncertainty evaluation-the ISO GUM modeling approach and
      the Nordtest approach. This tutorial is expected to be of interest to workers in
      different fields of science who use measurements with amperometric sensors and
      need to evaluate the uncertainty of the obtained results but are new to the
      concept of measurement uncertainty. The tutorial is also expected to be educative
      in order to make measurement results more accurate.

PMID- 22399888
TI  - Common Criteria related security design patterns--validation on the intelligent
      sensor example designed for mine environment.
AB  - The paper discusses the security issues of intelligent sensors that are able to
      measure and process data and communicate with other information technology (IT)
      devices or systems. Such sensors are often used in high risk applications. To
      improve their robustness, the sensor systems should be developed in a restricted
      way to provide them with assurance. One of assurance creation methodologies is
      Common Criteria (ISO/IEC 15408), used for IT products and systems. The
      contribution of the paper is a Common Criteria compliant and pattern-based method
      for the intelligent sensors security development. The paper concisely presents
      this method and its evaluation for the sensor detecting methane in a mine,
      focusing on the security problem of the intelligent sensor definition and
      solution. The aim of the validation is to evaluate and improve the introduced
      method.

PMID- 22399889
TI  - Adaptive square-shaped trajectory-based service location protocol in wireless
      sensor networks.
AB  - In this paper we propose an adaptive square-shaped trajectory (ASST)-based
      service location method to ensure load scalability in wireless sensor networks.
      This first establishes a square-shaped trajectory over the nodes that surround a
      target point computed by the hash function and any user can access it, using the
      hash. Both the width and the size of the trajectory are dynamically adjustable,
      depending on the number of queries made to the service information on the
      trajectory. The number of sensor nodes on the trajectory varies in proportion to
      the changing trajectory shape, allowing high loads to be distributed around the
      hot spot area.

PMID- 22399890
TI  - A multipath routing protocol based on clustering and ant colony optimization for
      wireless sensor networks.
AB  - For monitoring burst events in a kind of reactive wireless sensor networks
      (WSNs), a multipath routing protocol (MRP) based on dynamic clustering and ant
      colony optimization (ACO) is proposed. Such an approach can maximize the network
      lifetime and reduce the energy consumption. An important attribute of WSNs is
      their limited power supply, and therefore some metrics (such as energy
      consumption of communication among nodes, residual energy, path length) were
      considered as very important criteria while designing routing in the MRP.
      Firstly, a cluster head (CH) is selected among nodes located in the event area
      according to some parameters, such as residual energy. Secondly, an improved ACO
      algorithm is applied in the search for multiple paths between the CH and sink
      node. Finally, the CH dynamically chooses a route to transmit data with a
      probability that depends on many path metrics, such as energy consumption. The
      simulation results show that MRP can prolong the network lifetime, as well as
      balance of energy consumption among nodes and reduce the average energy
      consumption effectively.

PMID- 22399891
TI  - Design strategies for aptamer-based biosensors.
AB  - Aptamers have been widely used as recognition elements for biosensor
      construction, especially in the detection of proteins or small molecule targets,
      and regarded as promising alternatives for antibodies in bioassay areas. In this
      review, we present an overview of reported design strategies for the fabrication
      of biosensors and classify them into four basic modes: target-induced structure
      switching mode, sandwich or sandwich-like mode, target-induced
      dissociation/displacement mode and competitive replacement mode. In view of the
      unprecedented advantages brought about by aptamers and smart design strategies,
      aptamer-based biosensors are expected to be one of the most promising devices in
      bioassay related applications.

PMID- 22399893
TI  - Privacy-preserving data aggregation protocols for wireless sensor networks: a
      survey.
AB  - Many wireless sensor network (WSN) applications require privacy-preserving
      aggregation of sensor data during transmission from the source nodes to the sink
      node. In this paper, we explore several existing privacy-preserving data
      aggregation (PPDA) protocols for WSNs in order to provide some insights on their
      current status. For this, we evaluate the PPDA protocols on the basis of such
      metrics as communication and computation costs in order to demonstrate their
      potential for supporting privacy-preserving data aggregation in WSNs. In
      addition, based on the existing research, we enumerate some important future
      research directions in the field of privacy-preserving data aggregation for WSNs.

PMID- 22399894
TI  - Intelligent gearbox diagnosis methods based on SVM, wavelet lifting and RBR.
AB  - Given the problems in intelligent gearbox diagnosis methods, it is difficult to
      obtain the desired information and a large enough sample size to study;
      therefore, we propose the application of various methods for gearbox fault
      diagnosis, including wavelet lifting, a support vector machine (SVM) and rule
      based reasoning (RBR). In a complex field environment, it is less likely for
      machines to have the same fault; moreover, the fault features can also vary.
      Therefore, a SVM could be used for the initial diagnosis. First, gearbox
      vibration signals were processed with wavelet packet decomposition, and the
      signal energy coefficients of each frequency band were extracted and used as
      input feature vectors in SVM for normal and faulty pattern recognition. Second,
      precision analysis using wavelet lifting could successfully filter out the noisy
      signals while maintaining the impulse characteristics of the fault; thus
      effectively extracting the fault frequency of the machine. Lastly, the knowledge
      base was built based on the field rules summarized by experts to identify the
      detailed fault type. Results have shown that SVM is a powerful tool to accomplish
      gearbox fault pattern recognition when the sample size is small, whereas the
      wavelet lifting scheme can effectively extract fault features, and rule-based
      reasoning can be used to identify the detailed fault type. Therefore, a method
      that combines SVM, wavelet lifting and rule-based reasoning ensures effective
      gearbox fault diagnosis.

PMID- 22399892
TI  - Glucose biosensors: an overview of use in clinical practice.
AB  - Blood glucose monitoring has been established as a valuable tool in the
      management of diabetes. Since maintaining normal blood glucose levels is
      recommended, a series of suitable glucose biosensors have been developed. During
      the last 50 years, glucose biosensor technology including point-of-care devices,
      continuous glucose monitoring systems and noninvasive glucose monitoring systems
      has been significantly improved. However, there continues to be several
      challenges related to the achievement of accurate and reliable glucose
      monitoring. Further technical improvements in glucose biosensors, standardization
      of the analytical goals for their performance, and continuously assessing and
      training lay users are required. This article reviews the brief history, basic
      principles, analytical performance, and the present status of glucose biosensors
      in the clinical practice.

PMID- 22399895
TI  - A novel radar sensor for the non-contact detection of speech signals.
AB  - Different speech detection sensors have been developed over the years but they
      are limited by the loss of high frequency speech energy, and have restricted non
      contact detection due to the lack of penetrability. This paper proposes a novel
      millimeter microwave radar sensor to detect speech signals. The utilization of a
      high operating frequency and a superheterodyne receiver contributes to the high
      sensitivity of the radar sensor for small sound vibrations. In addition, the
      penetrability of microwaves allows the novel sensor to detect speech signals
      through nonmetal barriers. Results show that the novel sensor can detect high
      frequency speech energies and that the speech quality is comparable to
      traditional microphone speech. Moreover, the novel sensor can detect speech
      signals through a nonmetal material of a certain thickness between the sensor and
      the subject. Thus, the novel speech sensor expands traditional speech detection
      techniques and provides an exciting alternative for broader application
      prospects.

PMID- 22399896
TI  - Time delay for aerial ammonia concentration measurements in livestock buildings.
AB  - Correct measurements of ammonia concentration in air still present considerable
      challenges. The high water solubility and polarity can cause it to adsorb on
      surfaces in the entire sampling system, including sampling lines, filters,
      valves, pumps and instruments, causing substantial measuring errors and time
      delays. To estimate time delay characteristics of a Photo Acoustic Multi Gas
      Monitor 1312 and a Multi Point Sampler continuous measurement of aerial ammonia
      concentrations at different levels was performed. In order to obtain reproducible
      data, a wind tunnel was used to generate selected concentrations inside and a
      background concentration representing the air inlet of the tunnel. Four different
      concentration levels (0.8 ppm, 6.2 ppm, 9.7 ppm and 13.7 ppm) were used in the
      experiments, with an additional outdoor concentration level as background. The
      results indicated a substantial time delay when switching between the measuring
      positions with high and low concentration and vice versa. These properties may
      course serious errors for estimation of e.g. gas emissions whenever more than one
      measuring channel is applied. To reduce the measurement errors, some suggestions
      regarding design of the measurement setup and measuring strategies were
      presented.

PMID- 22399897
TI  - A novel pH-dependent drift improvement method for zirconium dioxide gated pH-ion
      sensitive field effect transistors.
AB  - A novel compensation method for Zirconium dioxide gated Ion Sensitive Field
      Effect Transistors (ISFETs) to improve pH-dependent drift was demonstrated.
      Through the sequential measurements for both the n-channel and p-channel ISFETs,
      75-100% pH-dependent drift could be successfully suppressed for the first seven
      hours. As a result, a nearly constant drift rate versus pH value was obtained,
      which increases the accuracy of pH measurements. Meanwhile, the drawback of the
      hyperbolic-like change with time of the common drift behavior for ISFETs was
      improved. A state-of-the-art integrated scheme adopting this method was also
      illustrated.

PMID- 22399898
TI  - State-of-the-art sensor technology in Spain: invasive and non-invasive techniques
      for monitoring respiratory variables.
AB  - The interest in measuring physiological parameters (especially arterial blood
      gases) has grown progressively in parallel to the development of new
      technologies. Physiological parameters were first measured invasively and at
      discrete time points; however, it was clearly desirable to measure them
      continuously and non-invasively. The development of intensive care units promoted
      the use of ventilators via oral intubation ventilators via oral intubation and
      mechanical respiratory variables were progressively studied. Later, the knowledge
      gained in the hospital was applied to out-of-hospital management. In the present
      paper we review the invasive and non-invasive techniques for monitoring
      respiratory variables.

PMID- 22399899
TI  - Classification of agarwood oil using an electronic nose.
AB  - Presently, the quality assurance of agarwood oil is performed by sensory panels
      which has significant drawbacks in terms of objectivity and repeatability. In
      this paper, it is shown how an electronic nose (e-nose) may be successfully
      utilised for the classification of agarwood oil. Hierarchical Cluster Analysis
      (HCA) and Principal Component Analysis (PCA), were used to classify different
      types of oil. The HCA produced a dendrogram showing the separation of e-nose data
      into three different groups of oils. The PCA scatter plot revealed a distinct
      separation between the three groups. An Artificial Neural Network (ANN) was used
      for a better prediction of unknown samples.

PMID- 22399900
TI  - Diode laser detection of greenhouse gases in the near-infrared region by
      wavelength modulation spectroscopy: pressure dependence of the detection
      sensitivity.
AB  - We have investigated the pressure dependence of the detection sensitivity of
      CO(2), N(2)O and CH(4) using wavelength modulation spectroscopy (WMS) with
      distributed feed-back diode lasers in the near infrared region. The spectral line
      shapes and the background noise of the second harmonics (2f) detection of the WMS
      were analyzed theoretically. We determined the optimum pressure conditions in the
      detection of CO(2), N(2)O and CH(4), by taking into consideration the background
      noise in the WMS. At the optimum total pressure for the detection of CO(2), N(2)O
      and CH(4), the limits of detection in the present system were determined.

PMID- 22399901
TI  - An overview of recent application of medical infrared thermography in sports
      medicine in Austria.
AB  - Medical infrared thermography (MIT) is used for analyzing physiological functions
      related to skin temperature. Technological advances have made MIT a reliable
      medical measurement tool. This paper provides an overview of MIT's technical
      requirements and usefulness in sports medicine, with a special focus on overuse
      and traumatic knee injuries. Case studies are used to illustrate the clinical
      applicability and limitations of MIT. It is concluded that MIT is a non-invasive,
      non-radiating, low cost detection tool which should be applied for pre-scanning
      athletes in sports medicine.

PMID- 22399903
TI  - Signal existence verification (SEV) for GPS low received power signal detection
      using the time-frequency approach.
AB  - The detection of low received power of global positioning system (GPS) signals in
      the signal acquisition process is an important issue for GPS applications.
      Improving the miss-detection problem of low received power signal is crucial,
      especially for urban or indoor environments. This paper proposes a signal
      existence verification (SEV) process to detect and subsequently verify low
      received power GPS signals. The SEV process is based on the time-frequency
      representation of GPS signal, and it can capture the characteristic of GPS signal
      in the time-frequency plane to enhance the GPS signal acquisition performance.
      Several simulations and experiments are conducted to show the effectiveness of
      the proposed method for low received power signal detection. The contribution of
      this work is that the SEV process is an additional scheme to assist the GPS
      signal acquisition process in low received power signal detection, without
      changing the original signal acquisition or tracking algorithms.

PMID- 22399904
TI  - Biosensing for the environment and defence: aqueous uranyl detection using
      bacterial surface layer proteins.
AB  - The fabrication of novel uranyl (UO(2)(2+)) binding protein based sensors is
      reported. The new biosensor responds to picomolar levels of aqueous uranyl ions
      within minutes using Lysinibacillus sphaericus JG-A12 S-layer protein tethered to
      gold electrodes. In comparison to traditional self assembled monolayer based
      biosensors the porous bioconjugated layer gave greater stability, longer
      electrode life span and a denser protein layer. Biosensors responded specifically
      to UO(2)(2+) ions and showed minor interference from Ni(2+), Cs(+), Cd(2+) and
      Co(2+). Chemical modification of JG-A12 protein phosphate and carboxyl groups
      prevented UO(2)(2+) binding, showing that both moieties are involved in the
      recognition to UO(2)(2+).

PMID- 22399905
TI  - Introduction to the special issue on "State-of-the-art sensor technology in
      Japan".

PMID- 22399906
TI  - Fiber Bragg grating sensor to monitor stress kinetics in drying process of
      commercial latex paints.
AB  - In this paper, we report a study about the application of packaged fiber Bragg
      gratings used as strain sensors to monitor the stress kinetics during the drying
      process of commercial latex paints. Three stages of drying with distinct
      mechanical deformation and temporal behaviors were identified for the samples,
      with mechanical deformation from 15 MUm to 21 MUm in the longitudinal film
      dimension on time intervals from 370 to 600 minutes. Drying time tests based on
      human sense technique described by the Brazilian Technical Standards NBR 9558
      were also done. The results obtained shows that human sense technique has a
      limited perception of the drying process and that the optical measurement system
      proposed can be used to characterize correctly the dry-through stage of paint.
      The influence of solvent (water) addition in the drying process was also
      investigated. The paint was diluted with four parts paint and one part water (80%
      paint), and one part paint and one part water (50% paint). It was observed that
      the increase of the water ratio mixed into the paint decreases both the
      mechanical deformation magnitude and the paint dry-through time. Contraction of
      5.2 MUm and 10.4 MUm were measured for concentrations of 50% and 80% of paint in
      the mixture, respectively. For both diluted paints the dry-through time was
      approximately 170 minutes less than undiluted paint. The optical technique
      proposed in this work can contribute to the development of new standards to
      specify the drying time of paint coatings.

PMID- 22399908
TI  - A multi-D-shaped optical fiber for refractive index sensing.
AB  - A novel class of multi-D-shaped optical fiber suited for refractive index
      measurements is presented. The multi-D-shaped optical fiber was constructed by
      forming several D-sections in a multimode optical fiber at localized regions with
      femtosecond laser pulses. The total number of D-shaped zones fabricated could
      range from three to seven. Each D-shaped zone covered a sensor volume of 100 MUm
      depth, 250 MUm width, and 1 mm length. The mean roughness of the core surface
      obtained by the AFM images was 231.7 nm, which is relatively smooth. Results of
      the tensile test indicated that the fibers have sufficient mechanical strength to
      resist damage from further processing. The multi-D-shaped optical fiber as a high
      sensitive refractive-index sensor to detect changes in the surrounding refractive
      index was studied. The results for different concentrations of sucrose solution
      show that a resolution of 1.27 * 10(-3)-3.13 * 10(-4) RIU is achieved for
      refractive indices in the range of 1.333 to 1.403, suggesting that the multi-D
      shaped fibers are attractive for chemical, biological, and biochemical sensing
      with aqueous solutions.

PMID- 22399907
TI  - A power-efficient bio-potential acquisition device with DS-MDE sensors for long
      term healthcare monitoring applications.
AB  - This work describes a power-efficient bio-potential acquisition device for long
      term healthcare applications that is implemented using novel
      microelectromechanical dry electrodes (MDE) and a low power bio-potential
      processing chip. Using micromachining technology, an attempt is also made to
      enhance the sensing reliability and stability by fabricating a diamond-shaped MDE
      (DS-MDE) that has a satisfactory self-stability capability and superior electric
      conductivity when attached onto skin without any extra skin tissue injury
      technology. To acquire differential bio-potentials such as ECG signals, the
      proposed processing chip fabricated in a standard CMOS process has a high common
      mode rejection ratio (C.M.R.R.) differential amplifier and a 12-bit analog-to
      digital converter (ADC). Use of the proposed system and integrate simple
      peripheral commercial devices can obtain the ECG signal efficiently without
      additional skin tissue injury and ensure continuous monitoring more than 70 hours
      with a 400 mAh battery.

PMID- 22399909
TI  - Real time speed estimation of moving vehicles from side view images from an
      uncalibrated video camera.
AB  - In order to estimate the speed of a moving vehicle with side view camera images,
      velocity vectors of a sufficient number of reference points identified on the
      vehicle must be found using frame images. This procedure involves two main steps.
      In the first step, a sufficient number of points from the vehicle is selected,
      and these points must be accurately tracked on at least two successive video
      frames. In the second step, by using the displacement vectors of the tracked
      points and passed time, the velocity vectors of those points are computed.
      Computed velocity vectors are defined in the video image coordinate system and
      displacement vectors are measured by the means of pixel units. Then the
      magnitudes of the computed vectors in image space should be transformed to the
      object space to find the absolute values of these magnitudes. This transformation
      requires an image to object space information in a mathematical sense that is
      achieved by means of the calibration and orientation parameters of the video
      frame images. This paper presents proposed solutions for the problems of using
      side view camera images mentioned here.

PMID- 22399910
TI  - Novel feature modelling the prediction and detection of sEMG muscle fatigue
      towards an automated wearable system.
AB  - Surface Electromyography (sEMG) activity of the biceps muscle was recorded from
      ten subjects performing isometric contraction until fatigue. A novel feature (1D
      spectro_std) was used to extract the feature that modeled three classes of
      fatigue, which enabled the prediction and detection of fatigue. Initial results
      of class separation were encouraging, discriminating between the three classes of
      fatigue, a longitudinal classification on Non-Fatigue and Transition-to-Fatigue
      shows 81.58% correct classification with accuracy 0.74 of correct predictions
      while the longitudinal classification on Transition-to-Fatigue and Fatigue showed
      lower average correct classification of 66.51% with a positive classification
      accuracy 0.73 of correct prediction. Comparison of the 1D spectro_std with other
      sEMG fatigue features on the same dataset show a significant improvement in
      classification, where results show a significant 20.58% (p < 0.01) improvement
      when using the 1D spectro_std to classify Non-Fatigue and Transition-to-Fatigue.
      In classifying Transition-to-Fatigue and Fatigue results also show a significant
      improvement over the other features giving 8.14% (p < 0.05) on average of all
      compared features.

PMID- 22399912
TI  - Solvent vapour detection with cholesteric liquid crystals--optical and mass
      sensitive evaluation of the sensor mechanism.
AB  - Cholesteric liquid crystals (CLCs) are used as sensitive coatings for the
      detection of organic solvent vapours for both polar and non-polar substances. The
      incorporation of different analyte vapours in the CLC layers disturbs the pitch
      length which changes the optical properties, i.e., shifting the absorption band.
      The engulfing of CLCs around non-polar solvent vapours such as tetrahedrofuran
      (THF), chloroform and tetrachloroethylene is favoured in comparison to polar
      ones, i.e., methanol and ethanol. Increasing solvent vapour concentrations shift
      the absorbance maximum to smaller wavelengths, e.g., as observed for THF.
      Additionally, CLCs have been coated on acoustic devices such as the quartz
      crystal microbalance (QCM) to measure the frequency shift of analyte samples at
      similar concentration levels. The mass effect for tetrachloroethylene was about
      six times higher than chloroform. Thus, optical response can be correlated with
      intercalation in accordance to mass detection. The mechanical stability was
      gained by combining CLCs with imprinted polymers. Therefore, pre-concentration of
      solvent vapours was performed leading to an additional selectivity.

PMID- 22399913
TI  - High sensitivity carbon nanotubes flow-rate sensors and their performance
      improvement by coating.
AB  - A new type of hot-wire flow-rate sensor (HWFS) with a sensing element made of a
      macro-sized carbon nanotube (CNT) strand is presented in this study. An effective
      way to improve repeatability of the CNT flow-rate sensor by coating a layer of
      Al(2)O(3) on the CNT surface is proposed. Experimental results show that due to
      the large surface-to-volume ratio and thin coated Al(2)O(3) layer, the CNT flow
      rate sensor has higher sensitivity and faster response than a conventional
      platinum (Pt) HWFS. It is also demonstrated that the covered CNT flow-rate sensor
      has better repeatability than its bare counterpart due to insulation from the
      surrounding environment. The proposed CNT flow-rate sensor shows application
      potential for high-sensitivity measurement of flow rate.

PMID- 22399911
TI  - A comprehensive review of glucose biosensors based on nanostructured metal
      oxides.
AB  - Nanotechnology has opened new and exhilarating opportunities for exploring
      glucose biosensing applications of the newly prepared nanostructured materials.
      Nanostructured metal-oxides have been extensively explored to develop biosensors
      with high sensitivity, fast response times, and stability for the determination
      of glucose by electrochemical oxidation. This article concentrates mainly on the
      development of different nanostructured metal-oxide [such as ZnO, Cu(I)/(II)
      oxides, MnO(2), TiO(2), CeO(2), SiO(2), ZrO(2,) and other metal-oxides] based
      glucose biosensors. Additionally, we devote our attention to the operating
      principles (i.e., potentiometric, amperometric, impedimetric and conductometric)
      of these nanostructured metal-oxide based glucose sensors. Finally, this review
      concludes with a personal prospective and some challenges of these nanoscaled
      sensors.

PMID- 22399914
TI  - Effect of atmospheric conditions on LIBS spectra.
AB  - Laser-induced breakdown spectroscopy (LIBS) is typically performed at ambient
      Earth atmospheric conditions. However, interest in LIBS in other atmospheric
      conditions has increased in recent years, especially for use in space exploration
      (e.g., Mars and Lunar) or to improve resolution for isotopic signatures. This
      review focuses on what has been reported about the performance of LIBS in reduced
      pressure environments as well as in various gases other than air.

PMID- 22399915
TI  - Comparative laser spectroscopy diagnostics for ancient metallic artefacts exposed
      to environmental pollution.
AB  - Metal artworks are subjected to corrosion and oxidation processes due to reactive
      agents present in the air, water and in the ground that these objects have been
      in contact with for hundreds of years. This is the case for archaeological metals
      that are recovered from excavation sites, as well as artefacts exposed to
      polluted air. Stabilization of the conservation state of these objects needs
      precise diagnostics of the accrued surface layers and identification of original,
      historical materials before further protective treatments, including safe laser
      cleaning of unwanted layers. This paper presents analyses of the chemical
      composition and stratigraphy of corrosion products with the use of laser induced
      breakdown spectroscopy (LIBS) and Raman spectroscopy. The discussion of the
      results is supported by material studies (SEM-EDS, XRF, ion-analyses). The tests
      were performed on several samples taken from original objects, including copper
      roofing from Wilanow Palace in Warsaw and Karol Poznanski Palace in LodY, bronze
      decorative figures from the Wilanow Palace gardens, and four archaeological
      examples of old jewellery (different copper alloys). Work has been performed as a
      part of the MATLAS project in the frames of EEA and Norway Grants (www.matlas.eu)
      and the results enable the comparison of the methodology and to elaborate the
      joint diagnostic procedures of the three project partner independent
      laboratories.

PMID- 22399916
TI  - Level set approach to anisotropic wet etching of silicon.
AB  - In this paper a methodology for the three dimensional (3D) modeling and
      simulation of the profile evolution during anisotropic wet etching of silicon
      based on the level set method is presented. Etching rate anisotropy in silicon is
      modeled taking into account full silicon symmetry properties, by means of the
      interpolation technique using experimentally obtained values for the etching
      rates along thirteen principal and high index directions in KOH solutions. The
      resulting level set equations are solved using an open source implementation of
      the sparse field method (ITK library, developed in medical image processing
      community), extended for the case of non-convex Hamiltonians. Simulation results
      for some interesting initial 3D shapes, as well as some more practical examples
      illustrating anisotropic etching simulation in the presence of masks (simple
      square aperture mask, convex corner undercutting and convex corner compensation,
      formation of suspended structures) are shown also. The obtained results show that
      level set method can be used as an effective tool for wet etching process
      modeling, and that is a viable alternative to the Cellular Automata method which
      now prevails in the simulations of the wet etching process.

PMID- 22399917
TI  - Testing ZigBee motes for monitoring refrigerated vegetable transportation under
      real conditions.
AB  - Quality control and monitoring of perishable goods during transportation and
      delivery services is an increasing concern for producers, suppliers, transport
      decision makers and consumers. The major challenge is to ensure a continuous
      'cold chain' from producer to consumer in order to guaranty prime condition of
      goods. In this framework, the suitability of ZigBee protocol for monitoring
      refrigerated transportation has been proposed by several authors. However, up to
      date there was not any experimental work performed under real conditions. Thus,
      the main objective of our experiment was to test wireless sensor motes based in
      the ZigBee/IEEE 802.15.4 protocol during a real shipment. The experiment was
      conducted in a refrigerated truck traveling through two countries (Spain and
      France) which means a journey of 1,051 kilometers. The paper illustrates the
      great potential of this type of motes, providing information about several
      parameters such as temperature, relative humidity, door openings and truck stops.
      Psychrometric charts have also been developed for improving the knowledge about
      water loss and condensation on the product during shipments.

PMID- 22399918
TI  - Detecting nano-scale vibrations in rotating devices by using advanced
      computational methods.
AB  - This paper presents a computational method for detecting vibrations related to
      eccentricity in ultra precision rotation devices used for nano-scale
      manufacturing. The vibration is indirectly measured via a frequency domain
      analysis of the signal from a piezoelectric sensor attached to the stationary
      component of the rotating device. The algorithm searches for particular harmonic
      sequences associated with the eccentricity of the device rotation axis. The
      detected sequence is quantified and serves as input to a regression model that
      estimates the eccentricity. A case study presents the application of the
      computational algorithm during precision manufacturing processes.

PMID- 22399919
TI  - Diffused Matrix Format: a new storage and processing format for airborne
      hyperspectral sensor images.
AB  - At present, hyperspectral images are mainly obtained with airborne sensors that
      are subject to turbulences while the spectrometer is acquiring the data.
      Therefore, geometric corrections are required to produce spatially correct images
      for visual interpretation and change detection analysis. This paper analyzes the
      data acquisition process of airborne sensors. The main objective is to propose a
      new data format called Diffused Matrix Format (DMF) adapted to the sensor's
      characteristics including its spectral and spatial information. The second
      objective is to compare the accuracy of the quantitative maps derived by using
      the DMF data structure with those obtained from raster images based on
      traditional data structures. Results show that DMF processing is more accurate
      and straightforward than conventional image processing of remotely sensed data
      with the advantage that the DMF file structure requires less storage space than
      other data formats. In addition the data processing time does not increase when
      DMF is used.

PMID- 22399921
TI  - Sensors: new challenges in Spain.

PMID- 22399920
TI  - Low light CMOS contact imager with an integrated poly-acrylic emission filter for
      fluorescence detection.
AB  - This study presents the fabrication of a low cost poly-acrylic acid (PAA) based
      emission filter integrated with a low light CMOS contact imager for fluorescence
      detection. The process involves the use of PAA as an adhesive for the emission
      filter. The poly-acrylic solution was chosen due its optical transparent
      properties, adhesive properties, miscibility with polar protic solvents and most
      importantly its bio-compatibility with a biological environment. The emission
      filter, also known as an absorption filter, involves dissolving an absorbing
      specimen in a polar protic solvent and mixing it with the PAA to uniformly bond
      the absorbing specimen and harden the filter. The PAA is optically transparent in
      solid form and therefore does not contribute to the absorbance of light in the
      visible spectrum. Many combinations of absorbing specimen and polar protic
      solvents can be derived, yielding different filter characteristics in different
      parts of the spectrum. We report a specific combination as a first example of
      implementation of our technology. The filter reported has excitation in the green
      spectrum and emission in the red spectrum, utilizing the increased quantum
      efficiency of the photo sensitive sensor array. The thickness of the filter (20
      MUm) was chosen by calculating the desired SNR using Beer-Lambert's law for
      liquids, Quantum Yield of the fluorophore and the Quantum Efficiency of the
      sensor array. The filters promising characteristics make it suitable for low
      light fluorescence detection. The filter was integrated with a fully functional
      low noise, low light CMOS contact imager and experimental results using
      fluorescence polystyrene micro-spheres are presented.

PMID- 22399923
TI  - A flexible proximity sensor fully fabricated by inkjet printing.
AB  - A flexible proximity sensor fully fabricated by inkjet printing is proposed in
      this paper. The flexible proximity sensor is composed of a ZnO layer sandwiched
      in between a flexible aluminum sheet and a web-shaped top electrode layer. The
      flexible aluminum sheet serves as the bottom electrode. The material of the top
      electrode layer is nano silver. Both the ZnO and top electrode layers are
      deposited by inkjet printing. The fully inkjet printing process possesses the
      advantages of direct patterning and low-cost. It does not require
      photolithography and etching processes since the pattern is directly printed on
      the flexible aluminum sheet. The prototype demonstrates that the presented
      flexible sensor is sensitive to the human body. It may be applied to proximity
      sensing or thermal eradiation sensing.

PMID- 22399924
TI  - Novel microwave-assisted synthesis of poly(D,L-lactide): the influence of
      monomer/initiator molar ratio on the product properties.
AB  - Poly(D,L-lactide) synthesis using tin(II) 2-ethylhexanoate initiated ring-opening
      polymerization (ROP) takes over 30 hours in bulk at 120  degrees C. The use of
      microwave makes the same bulk polymerization process with the same initiator much
      faster and energy saving, with a reaction time of about 30 minutes at 100 
      degrees C. Here, the poly(lactide) synthesis was done in a microwave reactor,
      using frequency of 2.45 GHz and maximal power of 150 W. The reaction temperature
      was controlled via infra-red system for in-bulk-measuring, and was maintained at
      100  degrees C. Different molar ratios of monomer and initiator, [M]/[I], of
      1,000, 5,000 and 10,000 were used. The achieved average molar masses for the
      obtained polymers (determined by gel permeation chromatography) were in the
      interval from 26,700 to 112,500 g/mol. The polydispersion index was from 2.436 to
      3.425. For applicative purposes, the obtained material was purified during the
      procedure of microsphere preparation. Microspheres were obtained by spraying a
      fine fog of polymer (D,L-lactide) solution in tetrahydrofuran into the water
      solution of poly(vinyl alcohol) with intensive stirring.

PMID- 22399922
TI  - Transcriptional regulation of glucose sensors in pancreatic beta-cells and liver:
      an update.
AB  - Pancreatic beta-cells and the liver play a key role in glucose homeostasis. After
      a meal or in a state of hyperglycemia, glucose is transported into the beta-cells
      or hepatocytes where it is metabolized. In the beta-cells, glucose is metabolized
      to increase the ATP:ADP ratio, resulting in the secretion of insulin stored in
      the vesicle. In the hepatocytes, glucose is metabolized to CO(2), fatty acids or
      stored as glycogen. In these cells, solute carrier family 2 (SLC2A2) and
      glucokinase play a key role in sensing and uptaking glucose. Dysfunction of these
      proteins results in the hyperglycemia which is one of the characteristics of type
      2 diabetes mellitus (T2DM). Thus, studies on the molecular mechanisms of their
      transcriptional regulations are important in understanding pathogenesis and
      combating T2DM. In this paper, we will review a recent update on the progress of
      gene regulation of glucose sensors in the liver and beta-cells.

PMID- 22399925
TI  - Characterization of mixed xWO3(1-x)Y2O3 nanoparticle thick film for gas sensing
      application.
AB  - Microstructural, topology, inner morphology, and gas-sensitivity of mixed
      xWO(3)(1-x)Y(2)O(3) nanoparticles (x = 1, 0.95, 0.9, 0.85, 0.8) thick-film
      semiconductor gas sensors were studied. The surface topography and inner
      morphological properties of the mixed powder and sensing film were characterized
      with X-ray diffraction (XRD), atomic force microscopy (AFM), transmission
      electron microscopy (TEM), and scanning electron microscopy (SEM). Also, gas
      sensitivity properties of the printed films were evaluated in the presence of
      methane (CH(4)) and butane (C(4)H(10)) at up to 500  degrees C operating
      temperature of the sensor. The results show that the doping agent can modify some
      structural properties and gas sensitivity of the mixed powder.

PMID- 22399926
TI  - Sonochemically fabricated microelectrode arrays for use as sensing platforms.
AB  - The development, manufacture, modification and subsequent utilisation of
      sonochemically-formed microelectrode arrays is described for a range of
      applications. Initial fabrication of the sensing platform utilises ultrasonic
      ablation of electrochemically insulating polymers deposited upon conductive
      carbon substrates, forming an array of up to 70,000 microelectrode pores cm(-2).
      Electrochemical and optical analyses using these arrays, their enhanced signal
      response and stir-independence area are all discussed. The growth of conducting
      polymeric "mushroom" protrusion arrays with entrapped biological entities,
      thereby forming biosensors is detailed. The simplicity and inexpensiveness of
      this approach, lending itself ideally to mass fabrication coupled with unrivalled
      sensitivity and stir independence makes commercial viability of this process a
      reality. Application of microelectrode arrays as functional components within
      sensors include devices for detection of chlorine, glucose, ethanol and
      pesticides. Immunosensors based on microelectrode arrays are described within
      this monograph for antigens associated with prostate cancer and transient
      ischemic attacks (strokes).

PMID- 22399927
TI  - Carbon nanostructure-based field-effect transistors for label-free
      chemical/biological sensors.
AB  - Over the past decade, electrical detection of chemical and biological species
      using novel nanostructure-based devices has attracted significant attention for
      chemical, genomics, biomedical diagnostics, and drug discovery applications. The
      use of nanostructured devices in chemical/biological sensors in place of
      conventional sensing technologies has advantages of high sensitivity, low
      decreased energy consumption and potentially highly miniaturized integration.
      Owing to their particular structure, excellent electrical properties and high
      chemical stability, carbon nanotube and graphene based electrical devices have
      been widely developed for high performance label-free chemical/biological
      sensors. Here, we review the latest developments of carbon nanostructure-based
      transistor sensors in ultrasensitive detection of chemical/biological entities,
      such as poisonous gases, nucleic acids, proteins and cells.

PMID- 22399928
TI  - A highly sensitive enzyme-amplified immunosensor based on a nanoporous niobium
      oxide (Nb2O5) electrode.
AB  - We report on the development of an enzyme-amplified sandwich-type immunosensor
      based on a thin gold film sputtered on an anodic nanoporous niobium oxide
      (Au@Nb(2)O(5)) electrode. The electrocatalytic activity of enzymatically
      amplified electroactive species and a stable electrode consisting of Au@Nb(2)O(5)
      were used to obtain a powerful signal amplification of the electrochemical
      immunobiosensor. The method using this electrochemical biosensor based on an
      Au@Nb(2)O(5) electrode provides a much better performance than those based on
      conventional bulk gold or niobium oxide electrodes. Our novel approach does not
      require any time-consuming cleaning steps to yield reproducible electrochemical
      signals. In addition, the strong adhesion of gold films on the niobium oxide
      electrodes offers a very stable substrate during electrochemical biosensing.
      Cyclic voltammetry measurements indicate that non-specific binding of proteins to
      the modified Au@Nb(2)O(5) surface is sufficiently low to be ignored in the case
      of our novel system. Finally, we demonstrated the ability of the biosensor based
      on an Au@Nb(2)O(5) offering the enhanced performance with a high resolution and
      sensitivity. Therefore, it is expected that the biosensor based on an
      Au@Nb(2)O(5) has great potential for highly efficient biological devices.

PMID- 22399929
TI  - A reusable PZT transducer for monitoring initial hydration and structural health
      of concrete.
AB  - During the construction of a concrete structure, strength monitoring is important
      to ensure the safety of both personnel and the structure. Furthermore, to
      increase the efficiency of in situ casting or precast of concrete, determining
      the optimal time of demolding is important for concrete suppliers. Surface bonded
      lead zirconate titanate (PZT) transducers have been used for damage detection and
      parameter identification for various engineering structures over the last two
      decades. In this work, a reusable PZT transducer setup for monitoring initial
      hydration of concrete and structural health is developed, where a piece of PZT is
      bonded to an enclosure with two bolts tightened inside the holes drilled in the
      enclosure. An impedance analyzer is used to acquire the admittance signatures of
      the PZT. Root mean square deviation (RMSD) is employed to associate the change in
      concrete strength with changes in the PZT admittance signatures. The results show
      that the reusable setup is able to effectively monitor the initial hydration of
      concrete and the structural health. It can also be detached from the concrete for
      future re-use.

PMID- 22399930
TI  - Estimation of visual maps with a robot network equipped with vision sensors.
AB  - In this paper we present an approach to the Simultaneous Localization and Mapping
      (SLAM) problem using a team of autonomous vehicles equipped with vision sensors.
      The SLAM problem considers the case in which a mobile robot is equipped with a
      particular sensor, moves along the environment, obtains measurements with its
      sensors and uses them to construct a model of the space where it evolves. In this
      paper we focus on the case where several robots, each equipped with its own
      sensor, are distributed in a network and view the space from different vantage
      points. In particular, each robot is equipped with a stereo camera that allow the
      robots to extract visual landmarks and obtain relative measurements to them. We
      propose an algorithm that uses the measurements obtained by the robots to build a
      single accurate map of the environment. The map is represented by the three
      dimensional position of the visual landmarks. In addition, we consider that each
      landmark is accompanied by a visual descriptor that encodes its visual
      appearance. The solution is based on a Rao-Blackwellized particle filter that
      estimates the paths of the robots and the position of the visual landmarks. The
      validity of our proposal is demonstrated by means of experiments with a team of
      real robots in a office-like indoor environment.

PMID- 22399931
TI  - NEURON: enabling autonomicity in wireless sensor networks.
AB  - Future Wireless Sensor Networks (WSNs) will be ubiquitous, large-scale networks
      interconnected with the existing IP infrastructure. Autonomic functionalities
      have to be designed in order to reduce the complexity of their operation and
      management, and support the dissemination of knowledge within a WSN. In this
      paper a novel protocol for energy efficient deployment, clustering and routing in
      WSNs is proposed that focuses on the incorporation of autonomic functionalities
      in the existing approaches. The design of the protocol facilitates the design of
      innovative applications and services that are based on overlay topologies created
      through cooperation among the sensor nodes.

PMID- 22399932
TI  - Basic test framework for the evaluation of text line segmentation and text
      parameter extraction.
AB  - Text line segmentation is an essential stage in off-line optical character
      recognition (OCR) systems. It is a key because inaccurately segmented text lines
      will lead to OCR failure. Text line segmentation of handwritten documents is a
      complex and diverse problem, complicated by the nature of handwriting. Hence,
      text line segmentation is a leading challenge in handwritten document image
      processing. Due to inconsistencies in measurement and evaluation of text
      segmentation algorithm quality, some basic set of measurement methods is
      required. Currently, there is no commonly accepted one and all algorithm
      evaluation is custom oriented. In this paper, a basic test framework for the
      evaluation of text feature extraction algorithms is proposed. This test framework
      consists of a few experiments primarily linked to text line segmentation, skew
      rate and reference text line evaluation. Although they are mutually independent,
      the results obtained are strongly cross linked. In the end, its suitability for
      different types of letters and languages as well as its adaptability are its main
      advantages. Thus, the paper presents an efficient evaluation method for text
      analysis algorithms.

PMID- 22399933
TI  - A Bayesian framework for human body pose tracking from depth image sequences.
AB  - This paper addresses the problem of accurate and robust tracking of 3D human body
      pose from depth image sequences. Recovering the large number of degrees of
      freedom in human body movements from a depth image sequence is challenging due to
      the need to resolve the depth ambiguity caused by self-occlusions and the
      difficulty to recover from tracking failure. Human body poses could be estimated
      through model fitting using dense correspondences between depth data and an
      articulated human model (local optimization method). Although it usually achieves
      a high accuracy due to dense correspondences, it may fail to recover from
      tracking failure. Alternately, human pose may be reconstructed by detecting and
      tracking human body anatomical landmarks (key-points) based on low-level depth
      image analysis. While this method (key-point based method) is robust and recovers
      from tracking failure, its pose estimation accuracy depends solely on image-based
      localization accuracy of key-points. To address these limitations, we present a
      flexible Bayesian framework for integrating pose estimation results obtained by
      methods based on key-points and local optimization. Experimental results are
      shown and performance comparison is presented to demonstrate the effectiveness of
      the proposed approach.

PMID- 22399934
TI  - Energy efficient sensor scheduling with a mobile sink node for the target
      tracking application.
AB  - Measurement losses adversely affect the performance of target tracking. The
      sensor network's life span depends on how efficiently the sensor nodes consume
      energy. In this paper, we focus on minimizing the total energy consumed by the
      sensor nodes whilst avoiding measurement losses. Since transmitting data over a
      long distance consumes a significant amount of energy, a mobile sink node
      collects the measurements and transmits them to the base station. We assume that
      the default transmission range of the activated sensor node is limited and it can
      be increased to maximum range only if the mobile sink node is out-side the
      default transmission range. Moreover, the active sensor node can be changed after
      a certain time period. The problem is to select an optimal sensor sequence which
      minimizes the total energy consumed by the sensor nodes. In this paper, we
      consider two different problems depend on the mobile sink node's path. First, we
      assume that the mobile sink node's position is known for the entire time horizon
      and use the dynamic programming technique to solve the problem. Second, the
      position of the sink node is varied over time according to a known Markov chain,
      and the problem is solved by stochastic dynamic programming. We also present sub
      optimal methods to solve our problem. A numerical example is presented in order
      to discuss the proposed methods' performance.

PMID- 22399935
TI  - Capture of Escherichia coli O157:H7 Using Immunomagnetic Beads of Different Size
      and Antibody Conjugating Chemistry.
AB  - Immunomagnetic beads (IMB) were synthesized using anti-Escherichia coli O157
      antibodies and magnetic beads of two different sizes (1 MUm and 2.6 to 2.8 MUm)
      that contained a streptavidin coating, activated carboxyl groups or tosylated
      surfaces. The synthesized IMB, together with a commercially available IMB, were
      used to capture different strains of E. coli O157:H7 and E. coli O157:NM. The E.
      coli capture was measured by the time resolved fluorescence (TRF) intensity using
      a sandwich assay which we have previously demonstrated of having a sensitivity of
      1 CFU/g after 4.5 hour enrichment [1]. The analyses of measured TRF intensity and
      determined antibody surface concentration indicated that larger beads provided
      higher response signals than smaller beads and were more effective in capturing
      the target of interest in pure culture and ground beef. In addition, while each
      type of IMB showed different favorable capture of E. coli O157:H7, streptavidin
      coated IMB elicited the highest response, on average. Streptavidin-coated IMB
      also provided an economic benefit, costing less than $0.50 per assay. The results
      could be used to guide the proper choice of IMB for applications in developing
      detection processes for E. coli O157:H7.

PMID- 22399936
TI  - Bayesian algorithm implementation in a real time exposure assessment model on
      benzene with calculation of associated cancer risks.
AB  - The objective of the current study was the development of a reliable modeling
      platform to calculate in real time the personal exposure and the associated
      health risk for filling station employees evaluating current environmental
      parameters (traffic, meteorological and amount of fuel traded) determined by the
      appropriate sensor network. A set of Artificial Neural Networks (ANNs) was
      developed to predict benzene exposure pattern for the filling station employees.
      Furthermore, a Physiology Based Pharmaco-Kinetic (PBPK) risk assessment model was
      developed in order to calculate the lifetime probability distribution of leukemia
      to the employees, fed by data obtained by the ANN model. Bayesian algorithm was
      involved in crucial points of both model sub compartments. The application was
      evaluated in two filling stations (one urban and one rural). Among several
      algorithms available for the development of the ANN exposure model, Bayesian
      regularization provided the best results and seemed to be a promising technique
      for prediction of the exposure pattern of that occupational population group. On
      assessing the estimated leukemia risk under the scope of providing a distribution
      curve based on the exposure levels and the different susceptibility of the
      population, the Bayesian algorithm was a prerequisite of the Monte Carlo
      approach, which is integrated in the PBPK-based risk model. In conclusion, the
      modeling system described herein is capable of exploiting the information
      collected by the environmental sensors in order to estimate in real time the
      personal exposure and the resulting health risk for employees of gasoline filling
      stations.

PMID- 22399937
TI  - Membrane Based Measurement Technology for in situ Monitoring of Gases in Soil.
AB  - The representative measurement of gas concentration and fluxes in heterogeneous
      soils is one of the current challenges when analyzing the interactions of
      biogeochemical processes in soils and global change. Furthermore, recent research
      projects on CO(2)-sequestration have an urgent need of CO(2)-monitoring networks.
      Therefore, a measurement method based on selective permeation of gases through
      tubular membranes has been developed. Combining the specific permeation rates of
      gas components for a membrane and Dalton's principle, the gas concentration (or
      partial pressure) can be determined by the measurement of physical quantities
      (pressure or volume) only. Due to the comparatively small permeation constants of
      membranes, the influence of the sensor on its surrounding area can be neglected.
      The design of the sensor membranes can be adapted to the spatial scale from the
      bench scale to the field scale. The sensitive area for the measurement can be
      optimized to obtain representative results. Furthermore, a continuous time
      averaged measurement is possible where the time for averaging is simply
      controlled by the wall-thickness of the membrane used. The measuring method is
      demonstrated for continuous monitoring of O(2) and CO(2) inside of a sand filled
      Lysimeter. Using three sensor planes inside the sand pack, which were installed
      normal to the gas flow direction and a reference measurement system, we
      demonstrate the accuracy of the gas-detection for different flux-based boundary
      conditions.

PMID- 22399938
TI  - Comparison Between Fractional Vegetation Cover Retrievals from Vegetation Indices
      and Spectral Mixture Analysis: Case Study of PROBA/CHRIS Data Over an
      Agricultural Area.
AB  - In this paper we compare two different methodologies for Fractional Vegetation
      Cover (FVC) retrieval from Compact High Resolution Imaging Spectrometer (CHRIS)
      data onboard the European Space Agency (ESA) Project for On-Board Autonomy
      (PROBA) platform. The first methodology is based on empirical approaches using
      Vegetation Indices (VIs), in particular the Normalized Difference Vegetation
      Index (NDVI) and the Variable Atmospherically Resistant Index (VARI). The second
      methodology is based on the Spectral Mixture Analysis (SMA) technique, in which a
      Linear Spectral Unmixing model has been considered in order to retrieve the
      abundance of the different constituent materials within pixel elements, called
      Endmembers (EMs). These EMs were extracted from the image using three different
      methods: i) manual extraction using a land cover map, ii) Pixel Purity Index
      (PPI) and iii) Automated Morphological Endmember Extraction (AMEE). The different
      methodologies for FVC retrieval were applied to one PROBA/CHRIS image acquired
      over an agricultural area in Spain, and they were calibrated and tested against
      in situ measurements of FVC estimated with hemispherical photographs. The results
      obtained from VIs show that VARI correlates better with FVC than NDVI does, with
      standard errors of estimation of less than 8% in the case of VARI and less than
      13% in the case of NDVI when calibrated using the in situ measurements. The
      results obtained from the SMA-LSU technique show Root Mean Square Errors (RMSE)
      below 12% when EMs are extracted from the AMEE method and around 9% when
      extracted from the PPI method. A RMSE value below 9% was obtained for manual
      extraction of EMs using a land cover use map.

PMID- 22399939
TI  - Performance of three reflectance calibration methods for airborne hyperspectral
      spectrometer data.
AB  - In this study, the performances and accuracies of three methods for converting
      airborne hyperspectral spectrometer data to reflectance factors were
      characterized and compared. The "reflectance mode (RM)" method, which calibrates
      a spectrometer against a white reference panel prior to mounting on an aircraft,
      resulted in spectral reflectance retrievals that were biased and distorted. The
      magnitudes of these bias errors and distortions varied significantly, depending
      on time of day and length of the flight campaign. The "linear-interpolation (LI)"
      method, which converts airborne spectrometer data by taking a ratio of linearly
      interpolated reference values from the preflight and post-flight reference panel
      readings, resulted in precise, but inaccurate reflectance retrievals. These
      reflectance spectra were not distorted, but were subject to bias errors of
      varying magnitudes dependent on the flight duration length. The "continuous panel
      (CP)" method uses a multi-band radiometer to obtain continuous measurements over
      a reference panel throughout the flight campaign, in order to adjust the
      magnitudes of the linear-interpolated reference values from the preflight and
      post-flight reference panel readings. Airborne hyperspectral reflectance
      retrievals obtained using this method were found to be the most accurate and
      reliable reflectance calibration method. The performances of the CP method in
      retrieving accurate reflectance factors were consistent throughout time of day
      and for various flight durations. Based on the dataset analyzed in this study,
      the uncertainty of the CP method has been estimated to be 0.0025 +/- 0.0005
      reflectance units for the wavelength regions not affected by atmospheric
      absorptions. The RM method can produce reasonable results only for a very short
      term flight (e.g., < 15 minutes) conducted around a local solar noon. The flight
      duration should be kept shorter than 30 minutes for the LI method to produce
      results with reasonable accuracies. An important advantage of the CP method is
      that the method can be used for long-duration flight campaigns (e.g., 1-2 hours).
      Although this study focused on reflectance calibration of airborne spectrometer
      data, the methods evaluated in this study and the results obtained are directly
      applicable to ground spectrometer measurements.

PMID- 22399940
TI  - A fast level set method for synthetic aperture radar ocean image segmentation.
AB  - Segmentation of high noise imagery like Synthetic Aperture Radar (SAR) images is
      still one of the most challenging tasks in image processing. While level set, a
      novel approach based on the analysis of the motion of an interface, can be used
      to address this challenge, the cell-based iterations may make the process of
      image segmentation remarkably slow, especially for large-size images. For this
      reason fast level set algorithms such as narrow band and fast marching have been
      attempted. Built upon these, this paper presents an improved fast level set
      method for SAR ocean image segmentation. This competent method is dependent on
      both the intensity driven speed and curvature flow that result in a stable and
      smooth boundary. Notably, it is optimized to track moving interfaces for keeping
      up with the point-wise boundary propagation using a single list and a method of
      fast up-wind scheme iteration. The list facilitates efficient insertion and
      deletion of pixels on the propagation front. Meanwhile, the local up-wind scheme
      is used to update the motion of the curvature front instead of solving partial
      differential equations. Experiments have been carried out on extraction of
      surface slick features from ERS-2 SAR images to substantiate the efficacy of the
      proposed fast level set method.

PMID- 22399941
TI  - Detection of seagrass distribution changes from 1991 to 2006 in xincun bay,
      hainan, with satellite remote sensing.
AB  - Seagrass distribution is a very important index for costal management and
      protection. Seagrass distribution changes can be used as indexes to analyze the
      reasons for the changes. In this paper, in situ hyperspectral observation and
      satellite images of QuickBird, CBERS (China Brazil Earth Resources Satellite
      data) and Landsat data were used to retrieve bio-optical models and seagrass
      (Enhalus acoroides, Thalassia hemperichii) distribution in Xincun Bay, Hainan
      province, and seagrass distribution changes from 1991 to 2006 were analyzed.
      Hyperspectral results showed that the spectral bands at 555, 635, 650 and 675 nm
      are sensitive to leaf area index (LAI). Seagrass detection with QuickBird was
      more accurate than that with Landsat TM and CBERS; five classes could be
      classified clearly and used as correction for seagrass remote sensing data from
      Landsat TM and CBERS. In order to better describe seagrass distribution changes,
      the seagrass distribution area was divided as three regions: region A connected
      with region B in 1991, however it separated in 1999 and was wholly separated in
      2001; seagrass in region C shrank gradually and could not be detected in 2006.
      Analysis of the reasons for seagrass reduction indicated it was mainly affected
      by aquaculture and typhoons and in recent years, by land use changes.

PMID- 22399942
TI  - Enhanced TDMA Based Anti-Collision Algorithm with a Dynamic Frame Size Adjustment
      Strategy for Mobile RFID Readers.
AB  - In the fields of production, manufacturing and supply chain management, Radio
      Frequency Identification (RFID) is regarded as one of the most important
      technologies. Nowadays, Mobile RFID, which is often installed in carts or
      forklift trucks, is increasingly being applied to the search for and checkout of
      items in warehouses, supermarkets, libraries and other industrial fields. In
      using Mobile RFID, since the readers are continuously moving, they can interfere
      with each other when they attempt to read the tags. In this study, we suggest a
      Time Division Multiple Access (TDMA) based anti-collision algorithm for Mobile
      RFID readers. Our algorithm automatically adjusts the frame size of each reader
      without using manual parameters by adopting the dynamic frame size adjustment
      strategy when collisions occur at a reader. Through experiments on a simulated
      environment for Mobile RFID readers, we show that the proposed method improves
      the number of successful transmissions by about 228% on average, compared with
      Colorwave, a representative TDMA based anti-collision algorithm.

PMID- 22399943
TI  - Performance of a diaphragmed microlens for a packaged microspectrometer.
AB  - This paper describes the design, fabrication, packaging and testing of a
      microlens integrated in a multi-layered MEMS microspectrometer. The microlens was
      fabricated using modified PDMS molding to form a suspended lens diaphragm.
      Gaussian beam propagation model was used to measure the focal length and quantify
      M(2) value of the microlens. A tunable calibration source was set up to measure
      the response of the packaged device. Dual wavelength separation by the packaged
      device was demonstrated by CCD imaging and beam profiling of the spectroscopic
      output. We demonstrated specific techniques to measure critical parameters of
      microoptics systems for future optimization of spectroscopic devices.

PMID- 22399944
TI  - Manufacture of a Polyaniline Nanofiber Ammonia Sensor Integrated with a Readout
      Circuit Using the CMOS-MEMS Technique.
AB  - This study presents the fabrication of a polyaniline nanofiber ammonia sensor
      integrated with a readout circuit on a chip using the commercial 0.35 MUm
      complementary metal oxide semiconductor (CMOS) process and a post-process. The
      micro ammonia sensor consists of a sensing resistor and an ammonia sensing film.
      Polyaniline prepared by a chemical polymerization method was adopted as the
      ammonia sensing film. The fabrication of the ammonia sensor needs a post-process
      to etch the sacrificial layers and to expose the sensing resistor, and then the
      ammonia sensing film is coated on the sensing resistor. The ammonia sensor, which
      is of resistive type, changes its resistance when the sensing film adsorbs or
      desorbs ammonia gas. A readout circuit is employed to convert the resistance of
      the ammonia sensor into the voltage output. Experimental results show that the
      sensitivity of the ammonia sensor is about 0.88 mV/ppm at room temperature.

PMID- 22399945
TI  - Direct electrochemistry of horseradish peroxidase-gold nanoparticles conjugate.
AB  - We have studied the direct electrochemistry of horseradish peroxidase (HRP)
      coupled to gold nanoparticles (AuNP) using electrochemical techniques, which
      provide some insight in the application of biosensors as tools for diagnostics
      because HRP is widely used in clinical diagnostics kits. AuNP capped with (i)
      glutathione and (ii) lipoic acid was covalently linked to HRP. The immobilized
      HRP/AuNP conjugate showed characteristic redox peaks at a gold electrode. It
      displayed good electrocatalytic response to the reduction of H(2)O(2), with good
      sensitivity and without any electron mediator. The covalent linking of HRP and
      AuNP did not affect the activity of the enzyme significantly. The response of the
      electrode towards the different concentrations of H(2)O(2) showed the
      characteristics of Michaelis Menten enzyme kinetics with an optimum pH between
      7.0 to 8.0. The preparation of the sensor involves single layer of enzyme, which
      can be carried out efficiently and is also highly reproducible when compared to
      other systems involving the layer-by-layer assembly, adsorption or encapsulation
      of the enzyme. The immobilized AuNP-HRP can be used for immunosensor
      applications.

PMID- 22399946
TI  - A real-time de-noising algorithm for e-noses in a wireless sensor network.
AB  - A wireless e-nose network system is developed for the special purpose of
      monitoring odorant gases and accurately estimating odor strength in and around
      livestock farms. This system is to simultaneously acquire accurate odor strength
      values remotely at various locations, where each node is an e-nose that includes
      four metal-oxide semiconductor (MOS) gas sensors. A modified Kalman filtering
      technique is proposed for collecting raw data and de-noising based on the output
      noise characteristics of those gas sensors. The measurement noise variance is
      obtained in real time by data analysis using the proposed slip windows average
      method. The optimal system noise variance of the filter is obtained by using the
      experiments data. The Kalman filter theory on how to acquire MOS gas sensors data
      is discussed. Simulation results demonstrate that the proposed method can adjust
      the Kalman filter parameters and significantly reduce the noise from the gas
      sensors.

PMID- 22399947
TI  - Routing in Wireless Sensor Networks Using an Ant Colony Optimization (ACO) Router
      Chip.
AB  - Wireless Sensor Networks consisting of nodes with limited power are deployed to
      gather useful information from the field. In WSNs it is critical to collect the
      information in an energy efficient manner. Ant Colony Optimization, a swarm
      intelligence based optimization technique, is widely used in network routing. A
      novel routing approach using an Ant Colony Optimization algorithm is proposed for
      Wireless Sensor Networks consisting of stable nodes. Illustrative examples,
      detailed descriptions and comparative performance test results of the proposed
      approach are included. The approach is also implemented to a small sized hardware
      component as a router chip. Simulation results show that proposed algorithm
      provides promising solutions allowing node designers to efficiently operate
      routing tasks.

PMID- 22399948
TI  - Modeling gross primary production of agro-forestry ecosystems by assimilation of
      satellite-derived information in a process-based model.
AB  - In this paper we present results obtained in the framework of a regional-scale
      analysis of the carbon budget of poplar plantations in Northern Italy. We
      explored the ability of the process-based model BIOME-BGC to estimate the gross
      primary production (GPP) using an inverse modeling approach exploiting eddy
      covariance and satellite data. We firstly present a version of BIOME-BGC coupled
      with the radiative transfer models PROSPECT and SAILH (named PROSAILH-BGC) with
      the aims of i) improving the BIOME-BGC description of the radiative transfer
      regime within the canopy and ii) allowing the assimilation of remotely-sensed
      vegetation index time series, such as MODIS NDVI, into the model. Secondly, we
      present a two-step model inversion for optimization of model parameters. In the
      first step, some key ecophysiological parameters were optimized against data
      collected by an eddy covariance flux tower. In the second step, important
      information about phenological dates and about standing biomass were optimized
      against MODIS NDVI. Results obtained showed that the PROSAILH-BGC allowed
      simulation of MODIS NDVI with good accuracy and that we described better the
      canopy radiation regime. The inverse modeling approach was demonstrated to be
      useful for the optimization of ecophysiological model parameters, phenological
      dates and parameters related to the standing biomass, allowing good accuracy of
      daily and annual GPP predictions. In summary, this study showed that assimilation
      of eddy covariance and remote sensing data in a process model may provide
      important information for modeling gross primary production at regional scale.

PMID- 22399949
TI  - Passive and self-powered autonomous sensors for remote measurements.
AB  - Autonomous sensors play a very important role in the environmental, structural,
      and medical fields. The use of this kind of systems can be expanded for several
      applications, for example in implantable devices inside the human body where it
      is impossible to use wires. Furthermore, they enable measurements in harsh or
      hermetic environments, such as under extreme heat, cold, humidity or corrosive
      conditions. The use of batteries as a power supply for these devices represents
      one solution, but the size, and sometimes the cost and unwanted maintenance
      burdens of replacement are important drawbacks. In this paper passive and self
      powered autonomous sensors for harsh or hermetical environments without batteries
      are discussed. Their general architectures are presented. Sensing strategies,
      communication techniques and power management are analyzed. Then, general
      building blocks of an autonomous sensor are presented and the design guidelines
      that such a system must follow are given. Furthermore, this paper reports
      different proposed applications of autonomous sensors applied in harsh or
      hermetic environments: two examples of passive autonomous sensors that use
      telemetric communication are proposed, the first one for humidity measurements
      and the second for high temperatures. Other examples of self-powered autonomous
      sensors that use a power harvesting system from electromagnetic fields are
      proposed for temperature measurements and for airflow speeds.

PMID- 22399950
TI  - A Contextual Fire Detection Algorithm for Simulated HJ-1B Imagery.
AB  - The HJ-1B satellite, which was launched on September 6, 2008, is one of the small
      ones placed in the constellation for disaster prediction and monitoring. HJ-1B
      imagery was simulated in this paper, which contains fires of various sizes and
      temperatures in a wide range of terrestrial biomes and climates, including RED,
      NIR, MIR and TIR channels. Based on the MODIS version 4 contextual algorithm and
      the characteristics of HJ-1B sensor, a contextual fire detection algorithm was
      proposed and tested using simulated HJ-1B data. It was evaluated by the
      probability of fire detection and false alarm as functions of fire temperature
      and fire area. Results indicate that when the simulated fire area is larger than
      45 m(2) and the simulated fire temperature is larger than 800 K, the algorithm
      has a higher probability of detection. But if the simulated fire area is smaller
      than 10 m(2), only when the simulated fire temperature is larger than 900 K, may
      the fire be detected. For fire areas about 100 m(2), the proposed algorithm has a
      higher detection probability than that of the MODIS product. Finally, the
      omission and commission error were evaluated which are important factors to
      affect the performance of this algorithm. It has been demonstrated that HJ-1B
      satellite data are much sensitive to smaller and cooler fires than MODIS or AVHRR
      data and the improved capabilities of HJ-1B data will offer a fine opportunity
      for the fire detection.

PMID- 22399951
TI  - Surface Acoustic Wave Ammonia Sensors Based on ST-cut Quartz under Periodic Al
      Structure.
AB  - Surface acoustic wave (SAW) devices are key components for sensing applications.
      SAW propagation under a periodic grating was investigated in this work. The
      theoretical method used here is the space harmonic method. We also applied the
      results of SAW propagation studied in this work to design a two-port resonator
      with an Al grating on ST-cut quartz. The measured frequency responses of the
      resonator were similar to the simulation ones. Then, the chemical interface of
      polyaniline/WO(3) composites was coated on the SAW sensor for ammonia detection.
      The SAW sensor responded to ammonia gas and could be regenerated using dry
      nitrogen.

PMID- 22399952
TI  - Apparent thixotropic properties of saline/glycerol drops with biotinylated
      antibodies on streptavidin-coated glass slides: implications for bacterial
      capture on antibody microarrays.
AB  - The thixotropic-like properties of saline/glycerol drops, containing biotinylated
      capture antibodies, on streptavidin-coated glass slides have been investigated,
      along with their implications for bacterial detection in a fluorescent microarray
      immunoassay. The thixotropic-like nature of 60:40 saline-glycerol semisolid
      droplets (with differing amounts of antibodies) was observed when bacteria were
      captured, and their presence detected using a fluorescently-labeled antibody.
      Semisolid, gel-like drops of biotinylated capture antibody became liquefied and
      moved, and then returned to semisolid state, during the normal immunoassay
      procedures for bacterial capture and detection. Streaking patterns were observed
      that indicated thixotropic-like characteristics, and this appeared to have
      allowed excess biotinylated capture antibody to participate in bacterial capture
      and detection. When developing a microarray for bacterial detection, this must be
      considered for optimization. For example, with the appropriate concentration of
      antibody (in this study, 0.125 ng/nL), spots with increased diameter at the point
      of contact printing (and almost no streaking) were produced, resulting in a
      maximal signal. With capture antibody concentrations greater than 0.125 ng/nL,
      the excess biotinylated capture antibody (i.e., that which was residing in the
      three-dimensional, semisolid droplet space above the surface) was utilized to
      capture more bacteria. Similarly, when the immunoassay was performed within a
      hydrophobic barrier (i.e., without a coverslip), brighter spots with increased
      signal were observed. In addition, when higher concentrations of cells (~10(8)
      cells/mL) were available for capture, the importance of unbound capture antibody
      in the semisolid droplets became apparent because washing off the excess, unbound
      biotinylated capture antibody before the immunoassay was performed reduced the
      signal intensity by nearly 50%. This reduction in signal was not observed with
      lower concentrations of cells (~10(6) cells/mL). With increased volumes of
      capture antibody, abnormal spots were visualized, along with decreased signal
      intensity, after bacterial detection, indicating that the increased droplet
      volume detrimentally affected the immunoassay.

PMID- 22399953
TI  - Efficient Chemical Sensing by Coupled Slot SOI Waveguides.
AB  - A guided-wave chemical sensor for the detection of environmental pollutants or
      biochemical substances has been designed. The sensor is based on an asymmetric
      directional coupler employing slot optical waveguides. The use of a nanometer
      guiding structure where optical mode is confined in a low-index region permits a
      very compact sensor (device area about 1200 MUm(2)) to be realized, having the
      minimum detectable refractive index change as low as 10(-5). Silicon-on-Insulator
      technology has been assumed in sensor design and a very accurate modelling
      procedure based on Finite Element Method and Coupled Mode Theory has been pointed
      out. Sensor design and optimization have allowed a very good trade-off between
      device length and sensitivity. Expected device sensitivity to glucose
      concentration change in an aqueous solution is of the order of 0.1 g/L.

PMID- 22399955
TI  - Discrepancy Between ASTER- and MODIS- Derived Land Surface Temperatures: Terrain
      Effects.
AB  - The MODerate resolution Imaging Spectroradiometer (MODIS) and the Advanced
      Spaceborne Thermal Emission Reflection Radiometer (ASTER) are onboard the same
      satellite platform NASA TERRA. Both MODIS and ASTER offer routine retrieval of
      land surface temperatures (LSTs), and the ASTER- and MODIS-retrieved LST products
      have been used worldwide. Because a large fraction of the earth surface consists
      of mountainous areas, variations in elevation, terrain slope and aspect angles
      can cause biases in the retrieved LSTs. However, terrain-induced effects are
      generally neglected in most satellite retrievals, which may generate discrepancy
      between ASTER and MODIS LSTs. In this paper, we reported the terrain effects on
      the LST discrepancy with a case examination over a relief area at the Loess
      Plateau of China. Results showed that the terrain-induced effects were not major,
      but nevertheless important for the total LST discrepancy. A large local slope did
      not necessarily lead to a large LST discrepancy. The angle of emitted radiance
      was more important than the angle of local slope in generating the LST
      discrepancy. Specifically, the conventional terrain correction may be unsuitable
      for densely vegetated areas. The distribution of ASTER-to-MODIS emissivity
      suggested that the terrain correction was included in the generalized split
      window (GSW) based approach used to rectify MODIS LSTs. Further study should
      include the classification-induced uncertainty in emissivity for reliable use of
      satellite-retrieved LSTs over relief areas.

PMID- 22399954
TI  - Recent advances in nanotechnology applied to biosensors.
AB  - In recent years there has been great progress the application of nanomaterials in
      biosensors. The importance of these to the fundamental development of biosensors
      has been recognized. In particular, nanomaterials such as gold nanoparticles,
      carbon nanotubes, magnetic nanoparticles and quantum dots have been being
      actively investigated for their applications in biosensors, which have become a
      new interdisciplinary frontier between biological detection and material science.
      Here we review some of the main advances in this field over the past few years,
      explore the application prospects, and discuss the issues, approaches, and
      challenges, with the aim of stimulating a broader interest in developing
      nanomaterial-based biosensors and improving their applications in disease
      diagnosis and food safety examination.

PMID- 22399956
TI  - Error in Radar-Derived Soil Moisture due to Roughness Parameterization: An
      Analysis Based on Synthetical Surface Profiles.
AB  - In the past decades, many studies on soil moisture retrieval from SAR
      demonstrated a poor correlation between the top layer soil moisture content and
      observed backscatter coefficients, which mainly has been attributed to
      difficulties involved in the parameterization of surface roughness. The present
      paper describes a theoretical study, performed on synthetical surface profiles,
      which investigates how errors on roughness parameters are introduced by standard
      measurement techniques, and how they will propagate through the commonly used
      Integral Equation Model (IEM) into a corresponding soil moisture retrieval error
      for some of the currently most used SAR configurations. Key aspects influencing
      the error on the roughness parameterization and consequently on soil moisture
      retrieval are: the length of the surface profile, the number of profile
      measurements, the horizontal and vertical accuracy of profile measurements and
      the removal of trends along profiles. Moreover, it is found that soil moisture
      retrieval with C-band configuration generally is less sensitive to inaccuracies
      in roughness parameterization than retrieval with L-band configuration.

PMID- 22399957
TI  - Enhanced photoelectrochemical detection of bioaffinity reactions by vertically
      oriented au nanobranches complexed with a biotinylated polythiophene derivative.
AB  - Four nanostructured Au electrodes were prepared by a simple and templateless
      electrochemical deposition technique. After complexing with a biotinylated
      polythiophene derivative (PTBL), photocurrent generation and performance of
      PTBL/Au-nanostructured electrodes as photoelectrochemical biosensors were
      investigated. Among these four nanostructured Au electrodes, vertically oriented
      nanobranches on the electrode significantly improved the photoelectric
      conversion, because the vertically oriented nanostructures not only benefit light
      harvesting but also the transfer of the photogenerated charge carriers. Owing to
      this advantaged nanostructure, the PTBL/Au-nanobranch electrode showed higher
      sensitivity and faster response times in the photoelectrochemical detection of a
      streptavidin-biotin affinity reaction compared to a PTBL/Au-nanoparticle
      electrode.

PMID- 22399958
TI  - 3D Digital Surveying and Modelling of Cave Geometry: Application to Paleolithic
      Rock Art.
AB  - 3D digital surveying and modelling of cave geometry represents a relevant
      approach for research, management and preservation of our cultural and geological
      legacy. In this paper, a multi-sensor approach based on a terrestrial laser
      scanner, a high-resolution digital camera and a total station is presented. Two
      emblematic caves of Paleolithic human occupation and situated in northern Spain,
      "Las Caldas" and "Pena de Candamo", have been chosen to put in practise this
      approach. As a result, an integral and multi-scalable 3D model is generated which
      may allow other scientists, pre-historians, geologists..., to work on two
      different levels, integrating different Paleolithic Art datasets: (1) a basic
      level based on the accurate and metric support provided by the laser scanner; and
      (2) a advanced level using the range and image-based modelling.

PMID- 22399959
TI  - An Updating System for the Gridded Population Database of China Based on Remote
      Sensing, GIS and Spatial Database Technologies.
AB  - The spatial distribution of population is closely related to land use and land
      cover (LULC) patterns on both regional and global scales. Population can be
      redistributed onto geo-referenced square grids according to this relation. In the
      past decades, various approaches to monitoring LULC using remote sensing and
      Geographic Information Systems (GIS) have been developed, which makes it possible
      for efficient updating of geo-referenced population data. A Spatial Population
      Updating System (SPUS) is developed for updating the gridded population database
      of China based on remote sensing, GIS and spatial database technologies, with a
      spatial resolution of 1 km by 1 km. The SPUS can process standard Moderate
      Resolution Imaging Spectroradiometer (MODIS L1B) data integrated with a Pattern
      Decomposition Method (PDM) and an LULC-Conversion Model to obtain patterns of
      land use and land cover, and provide input parameters for a Population
      Spatialization Model (PSM). The PSM embedded in SPUS is used for generating 1 km
      by 1 km gridded population data in each population distribution region based on
      natural and socio-economic variables. Validation results from finer township
      level census data of Yishui County suggest that the gridded population database
      produced by the SPUS is reliable.

PMID- 22399960
TI  - Piezoresistive sensitivity, linearity and resistance time drift of polysilicon
      nanofilms with different deposition temperatures.
AB  - Our previous research work indicated that highly boron doped polysilicon
      nanofilms (<=100 nm in thickness) have higher gauge factor (the maximum is ~34
      for 80 nm-thick films) and better temperature stability than common polysilicon
      films (>= 200nm in thickness) at the same doping levels. Therefore, in order to
      further analyze the influence of deposition temperature on the film structure and
      piezoresistance performance, the piezoresistive sensitivity, piezoresistive
      linearity (PRL) and resistance time drift (RTD) of 80 nm-thick highly boron doped
      polysilicon nanofilms (PSNFs) with different deposition temperatures were studied
      here. The tunneling piezoresistive model was established to explain the
      relationship between the measured gauge factors (GFs) and deposition temperature.
      It was seen that the piezoresistance coefficient (PRC) of composite grain
      boundaries is higher than that of grains and the magnitude of GF is dependent on
      the resistivity of grain boundary (GB) barriers and the weight of the resistivity
      of composite GBs in the film resistivity. In the investigations on PRL and RTD,
      the interstitial-vacancy (IV) model was established to model GBs as the
      accumulation of IV pairs. And the recrystallization of metastable IV pairs caused
      by material deformation or current excitation is considered as the prime reason
      for piezoresistive nonlinearity (PRNL) and RTD. Finally, the optimal deposition
      temperature for the improvement of film performance and reliability is about 620 
      degrees C and the high temperature annealing is not very effective in improving
      the piezoresistive performance of PSNFs deposited at lower temperatures.

PMID- 22399961
TI  - Detection of neolithic settlements in thessaly (Greece) through multispectral and
      hyperspectral satellite imagery.
AB  - Thessaly is a low relief region in Greece where hundreds of Neolithic
      settlements/tells called magoules were established from the Early Neolithic
      period until the Bronze Age (6,000 - 3,000 BC). Multi-sensor remote sensing was
      applied to the study area in order to evaluate its potential to detect Neolithic
      settlements. Hundreds of sites were geo-referenced through systematic GPS
      surveying throughout the region. Data from four primary sensors were used, namely
      Landsat ETM, ASTER, EO1 - HYPERION and IKONOS. A range of image processing
      techniques were originally applied to the hyperspectral imagery in order to
      detect the settlements and validate the results of GPS surveying. Although
      specific difficulties were encountered in the automatic classification of
      archaeological features composed by a similar parent material with the
      surrounding landscape, the results of the research suggested a different response
      of each sensor to the detection of the Neolithic settlements, according to their
      spectral and spatial resolution.

PMID- 22399962
TI  - Flexible electronics sensors for tactile multi-touching.
AB  - Flexible electronics sensors for tactile applications in multi-touch sensing and
      large scale manufacturing were designed and fabricated. The sensors are based on
      polyimide substrates, with thixotropy materials used to print organic resistances
      and a bump on the top polyimide layer. The gap between the bottom electrode layer
      and the resistance layer provides a buffer distance to reduce erroneous contact
      during large bending. Experimental results show that the top membrane with a bump
      protrusion and a resistance layer had a large deflection and a quick sensitive
      response. The bump and resistance layer provided a concentrated von Mises stress
      force and inertial force on the top membrane center. When the top membrane had no
      bump, it had a transient response delay time and took longer to reach steady
      state. For printing thick structures of flexible electronics sensors, diffusion
      effects and dimensional shrinkages can be improved by using a paste material with
      a high viscosity. Linear algorithm matrixes with Gaussian elimination and control
      system scanning were used for multi-touch detection. Flexible electronics sensors
      were printed with a resistance thickness of about 32 MUm and a bump thickness of
      about 0.2 mm. Feasibility studies show that printing technology is appropriate
      for large scale manufacturing, producing sensors at a low cost.

PMID- 22399963
TI  - SITHON: An Airborne Fire Detection System Compliant with Operational Tactical
      Requirements.
AB  - In response to the urging need of fire managers for timely information on fire
      location and extent, the SITHON system was developed. SITHON is a fully digital
      thermal imaging system, integrating INS/GPS and a digital camera, designed to
      provide timely positioned and projected thermal images and video data streams
      rapidly integrated in the GIS operated by Crisis Control Centres. This article
      presents in detail the hardware and software components of SITHON, and
      demonstrates the first encouraging results of test flights over the Sithonia
      Peninsula in Northern Greece. It is envisaged that the SITHON system will be soon
      operated onboard various airborne platforms including fire brigade airplanes and
      helicopters as well as on UAV platforms owned and operated by the Greek Air
      Forces.

PMID- 22399964
TI  - Improving Ship Detection with Polarimetric SAR based on Convolution between Co
      polarization Channels.
AB  - The convolution between co-polarization amplitude only data is studied to improve
      ship detection performance. The different statistical behaviors of ships and
      surrounding ocean are characterized a by two-dimensional convolution function (2D
      CF) between different polarization channels. The convolution value of the ocean
      decreases relative to initial data, while that of ships increases. Therefore the
      contrast of ships to ocean is increased. The opposite variation trend of ocean
      and ships can distinguish the high intensity ocean clutter from ships'
      signatures. The new criterion can generally avoid mistaken detection by a
      constant false alarm rate detector. Our new ship detector is compared with other
      polarimetric approaches, and the results confirm the robustness of the proposed
      method.

PMID- 22399965
TI  - Combining multiple algorithms for road network tracking from multiple source
      remotely sensed imagery: a practical system and performance evaluation.
AB  - In light of the increasing availability of commercial high-resolution imaging
      sensors, automatic interpretation tools are needed to extract road features.
      Currently, many approaches for road extraction are available, but it is
      acknowledged that there is no single method that would be successful in
      extracting all types of roads from any remotely sensed imagery. In this paper, a
      novel classification of roads is proposed, based on both the roads' geometrical,
      radiometric properties and the characteristics of the sensors. Subsequently, a
      general road tracking framework is proposed, and one or more suitable road
      trackers are designed or combined for each type of roads. Extensive experiments
      are performed to extract roads from aerial/satellite imagery, and the results
      show that a combination strategy can automatically extract more than 60% of the
      total roads from very high resolution imagery such as QuickBird and DMC images,
      with a time-saving of approximately 20%, and acceptable spatial accuracy. It is
      proven that a combination of multiple algorithms is more reliable, more efficient
      and more robust for extracting road networks from multiple-source remotely sensed
      imagery than the individual algorithms.

PMID- 22399966
TI  - Improvement of the Accuracy of InSAR Image Co-Registration Based On Tie Points -
      A Review.
AB  - Interferometric Synthetic Aperture Radar (InSAR) is a new measurement technology,
      making use of the phase information contained in the Synthetic Aperture Radar
      (SAR) images. InSAR has been recognized as a potential tool for the generation of
      digital elevation models (DEMs) and the measurement of ground surface
      deformations. However, many critical factors affect the quality of InSAR data and
      limit its applications. One of the factors is InSAR data processing, which
      consists of image co-registration, interferogram generation, phase unwrapping and
      geocoding. The co-registration of InSAR images is the first step and dramatically
      influences the accuracy of InSAR products. In this paper, the principle and
      processing procedures of InSAR techniques are reviewed. One of important factors,
      tie points, to be considered in the improvement of the accuracy of InSAR image co
      registration are emphatically reviewed, such as interval of tie points,
      extraction of feature points, window size for tie point matching and the
      measurement for the quality of an interferogram.

PMID- 22399967
TI  - A new method for node fault detection in wireless sensor networks.
AB  - Wireless sensor networks (WSNs) are an important tool for monitoring distributed
      remote environments. As one of the key technologies involved in WSNs, node fault
      detection is indispensable in most WSN applications. It is well known that the
      distributed fault detection (DFD) scheme checks out the failed nodes by
      exchanging data and mutually testing among neighbor nodes in this network., but
      the fault detection accuracy of a DFD scheme would decrease rapidly when the
      number of neighbor nodes to be diagnosed is small and the node's failure ratio is
      high. In this paper, an improved DFD scheme is proposed by defining new detection
      criteria. Simulation results demonstrate that the improved DFD scheme performs
      well in the above situation and can increase the fault detection accuracy
      greatly.

PMID- 22399968
TI  - An Improved Approach for Terrain Correction: Application to Northeast Asia's
      Highest Peak (Mt. Jade, Taiwan).
AB  - Mt. Jade (or "Yushan" in Chinese) is the highest peak in northeast Asia. The
      topography is very rugged and complicated. Such terrain makes it difficult to
      obtain the correct results for terrain corrections (TCs). This paper developed an
      improved approach, named cone-section method, to compute the TCs of the Mt. Jade
      area using a high-resolution digital elevation model (DEM) on a 9" * 9" grid. The
      corrections were calculated to the distance of 100 km with an average rock
      density of 2.57 * 10(3) kg.m(-3). This investigation compared the results of TCs
      from the cone-section method with those from the cylinder prism and Gaussian
      quadrature methods using a 9" * 9" elevation grid for the inner zone and a 90" *
      90" elevation grid for the outer zone. The inner and outer radii were set to 20
      and 200 km, respectively. The comparisons showed that the cone-section algorithm
      is consistent with the Gaussian quadrature. Furthermore, the cone-section method
      is an appropriate approach for TCs in high elevation areas, yielding results that
      outperform the cylinder prism method.

PMID- 22399969
TI  - An Electrochemical Sensor Based on Nanostructured Hollandite-type Manganese Oxide
      for Detection of Potassium Ions.
AB  - The participation of cations in redox reactions of manganese oxides provides an
      opportunity for development of chemical sensors for non-electroactive ions. A
      sensor based on a nanostructured hollandite-type manganese oxide was investigated
      for voltammetric detection of potassium ions. The detection is based on the
      measurement of anodic current generated by oxidation of Mn(III) to Mn(IV) at the
      surface of the electrode and the subsequent extraction of the potassium ions into
      the hollandite structure. In this work, an amperometric procedure at an operating
      potential of 0.80 V (versus SCE) is exploited for amperometric monitoring. The
      current signals are linearly proportional to potassium ion concentration in the
      range 4.97 * 10(-5) to 9.05 * 10(-4) mol L(-1), with a correlation coefficient of
      0.9997.

PMID- 22399970
TI  - Energy balanced strategies for maximizing the lifetime of sparsely deployed
      underwater acoustic sensor networks.
AB  - Underwater acoustic sensor networks (UWA-SNs) are envisioned to perform
      monitoring tasks over the large portion of the world covered by oceans. Due to
      economics and the large area of the ocean, UWA-SNs are mainly sparsely deployed
      networks nowadays. The limited battery resources is a big challenge for the
      deployment of such long-term sensor networks. Unbalanced battery energy
      consumption will lead to early energy depletion of nodes, which partitions the
      whole networks and impairs the integrity of the monitoring datasets or even
      results in the collapse of the entire networks. On the contrary, balanced energy
      dissipation of nodes can prolong the lifetime of such networks. In this paper, we
      focus on the energy balance dissipation problem of two types of sparsely deployed
      UWA-SNs: underwater moored monitoring systems and sparsely deployed two
      dimensional UWA-SNs. We first analyze the reasons of unbalanced energy
      consumption in such networks, then we propose two energy balanced strategies to
      maximize the lifetime of networks both in shallow and deep water. Finally, we
      evaluate our methods by simulations and the results show that the two strategies
      can achieve balanced energy consumption per node while at the same time prolong
      the networks lifetime.

PMID- 22399971
TI  - Sensing Characteristics of Flame-Spray-Made Pt/ZnO Thick Films as H(2) Gas
      Sensor.
AB  - Hydrogen sensing of thick films of nanoparticles of pristine, 0.2, 1.0 and 2.0
      atomic percentage of Pt concentration doped ZnO were investigated. ZnO
      nanoparticles doped with 0.2-2.0 at.% Pt were successfully produced in a single
      step by flame spray pyrolysis (FSP) technique using zinc naphthenate and
      platinum(II) acetylacetonate as precursors dissolved in xylene. The particle
      properties were analyzed by XRD, BET, SEM and TEM. Under the 5/5
      (precursor/oxygen) flame condition, ZnO nanoparticles and nanorods were observed.
      The crystallite sizes of ZnO spheroidal and hexagonal particles were found to be
      ranging from 5 to 20 nm while ZnO nanorods were seen to be 5-20 nm wide and 20-40
      nm long. ZnO nanoparticles paste composed of ethyl cellulose and terpineol as
      binder and solvent respectively was coated on Al(2)O(3) substrate interdigitated
      with gold electrodes to form thin films by spin coating technique. The thin film
      morphology was analyzed by SEM technique. The gas sensing properties toward
      hydrogen (H(2)) was found that the 0.2 at.% Pt/ZnO sensing film showed an optimum
      H(2) sensitivity of ~164 at hydrogen concentration in air of 1 volume% at 300 
      degrees C and a low hydrogen detection limit of 50 ppm at 300  degrees C
      operating temperature.

PMID- 22399972
TI  - Detecting the land-cover changes induced by large-physical disturbances using
      landscape metrics, spatial sampling, simulation and spatial analysis.
AB  - The objectives of the study are to integrate the conditional Latin Hypercube
      Sampling (cLHS), sequential Gaussian simulation (SGS) and spatial analysis in
      remotely sensed images, to monitor the effects of large chronological
      disturbances on spatial characteristics of landscape changes including spatial
      heterogeneity and variability. The multiple NDVI images demonstrate that spatial
      patterns of disturbed landscapes were successfully delineated by spatial analysis
      such as variogram, Moran'I and landscape metrics in the study area. The hybrid
      method delineates the spatial patterns and spatial variability of landscapes
      caused by these large disturbances. The cLHS approach is applied to select
      samples from Normalized Difference Vegetation Index (NDVI) images from SPOT HRV
      images in the Chenyulan watershed of Taiwan, and then SGS with sufficient samples
      is used to generate maps of NDVI images. In final, the NDVI simulated maps are
      verified using indexes such as the correlation coefficient and mean absolute
      error (MAE). Therefore, the statistics and spatial structures of multiple NDVI
      images present a very robust behavior, which advocates the use of the index for
      the quantification of the landscape spatial patterns and land cover change. In
      addition, the results transferred by Open Geospatial techniques can be accessed
      from web-based and end-user applications of the watershed management.

PMID- 22399973
TI  - Fabrication of a Multi-Walled Nanotube (MWNT) Ionic Liquid Electrode and Its
      Application for Sensing Phenolics in Red Wines.
AB  - A multi-walled nanotube (MWNT) ionic liquid was prepared by the immobilization of
      1-butylimidazole bromide onto an epoxy group on a poly(glycidyl methacrylate)
      grafted MWNT, which was synthesized by radiation-induced graft polymerization of
      glycidyl methacrylate onto MWNT in an aqueous solution. Subsequently, a MWNT
      ionic liquid electrode was fabricated by hand-casting MWNT ionic liquid,
      tyrosinase, and chitosan solution as a binder on indium tin oxide (ITO) glass.
      The sensing ranges of the MWNT ionic liquid electrode with immobilized tyrosinase
      was in the range of 0.01-0.08 mM in a phosphate buffer solution. The optimal
      conditions such as pH, temperature, and effects of different phenolic compounds
      were determined. The total phenolic compounds of three commercial red wines were
      also determined on the tyrosinase-immobilized biosensor.

PMID- 22399975
TI  - On the application of different event-based sampling strategies to the control of
      a simple industrial process.
AB  - This paper is an experimental study of the utilization of different event-based
      strategies for the automatic control of a simple but very representative
      industrial process: the level control of a tank. In an event-based control
      approach it is the triggering of a specific event, and not the time, that
      instructs the sensor to send the current state of the process to the controller,
      and the controller to compute a new control action and send it to the actuator.
      In the document, five control strategies based on different event-based sampling
      techniques are described, compared, and contrasted with a classical time-based
      control approach and a hybrid one. The common denominator in the time, the
      hybrid, and the event-based control approaches is the controller: a proportional
      integral algorithm with adaptations depending on the selected control approach.
      To compare and contrast each one of the hybrid and the pure event-based control
      algorithms with the time-based counterpart, the two tasks that a control strategy
      must achieve (set-point following and disturbance rejection) are independently
      analyzed. The experimental study provides new proof concerning the ability of
      event-based control strategies to minimize the data exchange among the control
      agents (sensors, controllers, actuators) when an error-free control of the
      process is not a hard requirement.

PMID- 22399974
TI  - Dendritic cells as danger-recognizing biosensors.
AB  - Dendritic cells (DCs) are antigen presenting cells that are characterized by a
      potent capacity to initiate immune responses. DCs comprise several subsets with
      distinct phenotypes. After sensing any danger(s) to the host via their innate
      immune receptors such as Toll-like receptors, DCs become mature and subsequently
      present antigens to CD4(+) T cells. Since DCs possess the intrinsic capacity to
      polarize CD4(+) helper cells, it is critical to understand the immunological
      roles of DCs for clinical applications. Here, we review the different DC subsets,
      their danger-sensing receptors and immunological functions. Furthermore, the
      cytokine reporter mouse model for studying DC activation is introduced.

PMID- 22399976
TI  - Optical sensors based on whispering gallery modes in fluorescent microbeads: size
      dependence and influence of substrate.
AB  - Whispering gallery modes in surface-fixated fluorescent polystyrene microbeads
      are studied in view of their capability of sensing changes in the refractive
      index of the beads' environment by exposing them to water/glycerol mixtures of
      varying composition. The mode positions are analyzed by simultaneous fitting for
      mode number, bead radius, and environmental index. Down to a diameter of 8 MUm,
      the sensor response follows the index of the bulk solution very well. For smaller
      bead sizes, some deviations occur, in particular for fluid indices not too
      different from that of water, which might be attributed to the presence of the
      substrate.

PMID- 22399977
TI  - The effects of two thick film deposition methods on tin dioxide gas sensor
      performance.
AB  - This work demonstrates the variability in performance between SnO(2) thick film
      gas sensors prepared using two types of film deposition methods. SnO(2) powders
      were deposited on sensor platforms with and without the use of binders. Three
      commonly utilized binder recipes were investigated, and a new binder-less
      deposition procedure was developed and characterized. The binder recipes yielded
      sensors with poor film uniformity and poor structural integrity, compared to the
      binder-less deposition method. Sensor performance at a fixed operating
      temperature of 330  degrees C for the different film deposition methods was
      evaluated by exposure to 500 ppm of the target gas carbon monoxide. A consequence
      of the poor film structure, large variability and poor signal properties were
      observed with the sensors fabricated using binders. Specifically, the sensors
      created using the binder recipes yielded sensor responses that varied widely
      (e.g., S = 5 - 20), often with hysteresis in the sensor signal. Repeatable and
      high quality performance was observed for the sensors prepared using the binder
      less dispersion-drop method with good sensor response upon exposure to 500 ppm CO
      (S = 4.0) at an operating temperature of 330  degrees C, low standard deviation
      to the sensor response (+/-0.35) and no signal hysteresis.

PMID- 22399978
TI  - Detecting specific health-related events using an integrated sensor system for
      vital sign monitoring.
AB  - In this paper, a new method for the detection of apnea/hypopnea periods in
      physiological data is presented. The method is based on the intelligent
      combination of an integrated sensor system for long-time cardiorespiratory signal
      monitoring and dedicated signal-processing packages. Integrated sensors are a
      PVDF film and conductive fabric sheets. The signal processing package includes
      dedicated respiratory cycle (RC) and QRS complex detection algorithms and a new
      method using the respiratory cycle variability (RCV) for detecting apnea/hypopnea
      periods in physiological data. Results show that our method is suitable for
      online analysis of long time series data.

PMID- 22399979
TI  - Changes in physiological parameters induced by indoor simulated driving: effect
      of lower body exercise at mid-term break.
AB  - The study monitored physiological parameter changes after 120-min of simulated
      driving. Blood pressures, heart rate (HR), heart rate variability (HRV) and palm
      temperatures were measured using an ANSWatch((r)) monitor. Subjects were divided
      into two groups (A & B). Both groups performed 2-hour driving, but group B
      additionally took a 15-min exercise break. Heart rate, systolic pressure, LF/HF,
      and palm temperature decreased for group A after driving; for group B only HR and
      palm temperatures decreased. HRV and parasympathetic indices HF(AU) and HF(NU)
      increased for group A, while HRV and sympathetic index LF(AU) increased in group
      B. Group A had higher fatigue scores than group B. ANS activation may overcome
      some fatigue symptoms, but the recovery is nonetheless incomplete. Exercise break
      is proven to be an effective remedy, especially if accompanied by the ANS
      actions. The normalized parasympathetic index HF(NU), the normalized sympathetic
      index LF(NU), and the sympatho-vagal balance index LF/HF are three most promising
      parameters that could be further developed to monitor driver fatigue.

PMID- 22399980
TI  - Silver(I) ions ultrasensitive detection at carbon electrodes-analysis of waters,
      tobacco cells and fish tissues.
AB  - We used carbon paste electrodes and a standard potentiostat to detect silver
      ions. The detection limit (3 Signal/Noise ratio) was estimated as 0.5 MUM. A
      standard electrochemical instrument microanalysis of silver(I) ions was
      suggested. As a working electrode a carbon tip (1 mL) or carbon pencil was used.
      Limits of detection estimated by dilution of a standard were 1 (carbon tip) or 10
      nM (carbon pencil). Further we employed flow injection analysis coupled with
      carbon tip to detect silver(I) ions released in various beverages and mineral
      waters. During first, second and third week the amount of silver(I) ions
      releasing into water samples was under the detection limit of the technique used
      for their quantification. At the end of a thirteen weeks long experiment the
      content of silver(I) ions was several times higher compared to the beginning of
      release detected in the third week and was on the order of tens of nanomoles. In
      subsequent experiments the influence of silver(I) ions (0, 5 and 10 MUM) on a
      plant model system (tobacco BY-2 cells) during a four-day exposition was
      investigated. Silver(I) ions were highly toxic to the cells, which was revealed
      by a double staining viability assay. Moreover we investigated the effect of
      silver(I) ions (0, 0.3, 0.6, 1.2 and 2.5 MUM) on guppies (Poecilia reticulata).
      Content of Ag(I) increased with increasing time of the treatment and applied
      concentrations in fish tissues. It can be concluded that a carbon tip or carbon
      pencil coupled with a miniaturized potentiostat can be used for detection of
      silver(I) ions in environmental samples and thus represents a small, portable,
      low cost and easy-to-use instrument for such purposes.

PMID- 22399981
TI  - Design and Analyses of a MEMS Based Resonant Magnetometer.
AB  - A novel design of a MEMS torsional resonant magnetometer based on Lorentz force
      is presented and fabricated. The magnetometer consists of a silicon resonator,
      torsional beam, excitation coil, capacitance plates and glass substrate. Working
      in a resonant condition, the sensor's vibration amplitude is converted into the
      sensing capacitance change, which reflects the outside magnetic flux-density.
      Based on the simulation, the key structure parameters are optimized and the air
      damping effect is estimated. The test results of the prototype are in accordance
      with the simulation results of the designed model. The resolution of the
      magnetometer can reach 30 nT. The test results indicate its sensitivity of more
      than 400 mV/MUT when operating in a 10 Pa vacuum environment.

PMID- 22399983
TI  - Application of close range photogrammetry to deck measurement in recreational
      ships.
AB  - In this article, we present results that demonstrate the utility of close range
      photogrammetry in the measurement of decks in recreational craft as an alternate
      measurement system to the one based on direct acquisition of coordinates. The
      areas of deck covered with teakwood for aesthetic or security reasons were
      measured. Both methods were compared in terms of precision of measurements, time
      consumption, equipment cost, and ease of manipulation and equipment
      transportation. Based on the results, we conclude that photogrammetry has
      advantages in almost every aspect with respect to the direct method.
      Consequently, photogrammetry is suggested as a suitable method for coordinate
      measurement of decks in recreational ships. However, in some special
      circumstances, where ships have wide corridors with few obstacles the direct
      method can be more appropriate than the photogrammetric method.

PMID- 22399984
TI  - On-line metrology with conoscopic holography: beyond triangulation.
AB  - On-line non-contact surface inspection with high precision is still an open
      problem. Laser triangulation techniques are the most common solution for this
      kind of systems, but there exist fundamental limitations to their applicability
      when high precisions, long standoffs or large apertures are needed, and when
      there are difficult operating conditions. Other methods are, in general, not
      applicable in hostile environments or inadequate for on-line measurement. In this
      paper we review the latest research in Conoscopic Holography, an interferometric
      technique that has been applied successfully in this kind of applications,
      ranging from submicrometric roughness measurements, to long standoff sensors for
      surface defect detection in steel at high temperatures.

PMID- 22399982
TI  - Gram-negative bacterial sensors for eukaryotic signal molecules.
AB  - Ample evidence exists showing that eukaryotic signal molecules synthesized and
      released by the host can activate the virulence of opportunistic pathogens. The
      sensitivity of prokaryotes to host signal molecules requires the presence of
      bacterial sensors. These prokaryotic sensors, or receptors, have a double
      function: stereospecific recognition in a complex environment and transduction of
      the message in order to initiate bacterial physiological modifications. As
      messengers are generally unable to freely cross the bacterial membrane, they
      require either the presence of sensors anchored in the membrane or transporters
      allowing direct recognition inside the bacterial cytoplasm. Since the discovery
      of quorum sensing, it was established that the production of virulence factors by
      bacteria is tightly growth-phase regulated. It is now obvious that expression of
      bacterial virulence is also controlled by detection of the eukaryotic messengers
      released in the micro-environment as endocrine or neuro-endocrine modulators. In
      the presence of host physiological stress many eukaryotic factors are released
      and detected by Gram-negative bacteria which in return rapidly adapt their
      physiology. For instance, Pseudomonas aeruginosa can bind elements of the host
      immune system such as interferon-gamma and dynorphin and then through quorum
      sensing circuitry enhance its virulence. Escherichia coli sensitivity to the
      neurohormones of the catecholamines family appears relayed by a recently
      identified bacterial adrenergic receptor. In the present review, we will describe
      the mechanisms by which various eukaryotic signal molecules produced by host may
      activate Gram-negative bacteria virulence. Particular attention will be paid to
      Pseudomonas, a genus whose representative species, P. aeruginosa, is a common
      opportunistic pathogen. The discussion will be particularly focused on the
      pivotal role played by these new types of pathogen sensors from the sensing to
      the transduction mechanism involved in virulence factors regulation. Finally, we
      will discuss the consequence of the impact of host signal molecules on
      commensally or opportunistic pathogens associated with different human tissue.

PMID- 22399987
TI  - Using the optical mouse sensor as a two-euro counterfeit coin detector.
AB  - In this paper, the sensor of an optical mouse is presented as a counterfeit coin
      detector applied to the two-Euro case. The detection process is based on the
      short distance image acquisition capabilities of the optical mouse sensor where
      partial images of the coin under analysis are compared with some partial
      reference coin images for matching. Results show that, using only the vision
      sense, the counterfeit acceptance and rejection rates are very similar to those
      of a trained user and better than those of an untrained user.

PMID- 22399985
TI  - Escherichia coli, an Intestinal Microorganism, as a Biosensor for Quantification
      of Amino Acid Bioavailability.
AB  - In animal diets optimal amino acid quantities and balance among amino acids is of
      great nutritional importance. Essential amino acid deficiencies have negative
      impacts on animal physiology, most often expressed in sub-optimal body weight
      gains. Over supplementation of diets with amino acids is costly and can increase
      the nitrogen emissions from animals. Although in vivo animal assays for
      quantification of amino acid bioavailability are well established, Escherichia
      coli-based bioassays are viable potential alternatives in terms of accuracy,
      cost, and time input. E. coli inhabits the gastrointestinal tract and although
      more abundant in colon, a relatively high titer of E. coli can also be isolated
      from the small intestine, where primary absorption of amino acids and peptides
      occur. After feed proteins are digested, liberated amino acids and small peptides
      are assimilated by both the small intestine and E. coli. The similar pattern of
      uptake is a necessary prerequisite to establish E. coli cells as accurate amino
      acid biosensors. In fact, amino acid transporters in both intestinal and E. coli
      cells are stereospecific, delivering only the respective biological l-forms. The
      presence of free amino- and carboxyl groups is critical for amino acid and
      dipeptide transport in both biological subjects. Di-, tri- and tetrapeptides can
      enter enterocytes; likewise only di-, tri- and tetrapeptides support E. coli
      growth. These similarities in addition to the well known bacterial genetics make
      E. coli an optimal bioassay microorganism for the assessment of nutritionally
      available amino acids in feeds.

PMID- 22399986
TI  - Preparation of a nanosized as(2)o(3)/mn(0.5)zn(0.5)fe(2)o(4) complex and its anti
      tumor effect on hepatocellular carcinoma cells.
AB  - Manganese-zinc-ferrite nanoparticles (Mn(0.5)Zn(0.5)Fe(2)O(4), MZF-NPs) prepared
      by an improved co-precipitation method and were characterized by transmission
      electron microscopy (TEM), X-ray diffraction (XRD) and energy dispersive
      spectrometry (EDS). Then thermodynamic testing of various doses of MZF-NPs was
      performed in vitro. The cytotoxicity of the Mn(0.5)Zn(0.5)Fe(2)O(4) nanoparticles
      in vitro was tested by the MTT assay. A nanosized
      As(2)O(3)/Mn(0.5)Zn(0.5)Fe(2)O(4) complex was made by an impregnation process.
      The complex's shape, component, envelop rate and release rate of As(2)O(3) were
      measured by SEM, EDS and atom fluorescence spectrometry, respectively. The
      therapeutic effect of nanosized As(2)O(3)/Mn(0.5)Zn(0.5)Fe(2)O(4) complex
      combined with magnetic fluid hyperthermia (MFH) on human hepatocelluar cells were
      evaluated in vitro by an MTT assay and flow cytometry. The results indicated that
      Mn(0.5)Zn(0.5)Fe(2)O(4) and nanosized As(2)O(3)/Mn(0.5)Zn(0.5)Fe(2)O(4) complex
      were both prepared successfully. The Mn(0.5)Zn(0.5)Fe(2)O(4) nanoparticles had
      powerful absorption capabilities in a high-frequency alternating electromagnetic
      field, and had strong magnetic responsiveness. Moreover, Mn(0.5)Zn(0.5)Fe(2)O(4)
      didn't show cytotoxicity in vitro. The therapeutic result reveals that the
      nanosized As(2)O(3)/Mn(0.5)Zn(0.5)Fe(2)O(4) complex can significantly inhibit the
      growth of hepatoma carcinoma cells.

PMID- 22399988
TI  - Photocurable polymers for ion selective field effect transistors. 20 years of
      applications.
AB  - Application of photocurable polymers for encapsulation of ion selective field
      effect transistors (ISFET) and for membrane formation in chemical sensitive field
      effect transistors (ChemFET) during the last 20 years is discussed. From a
      technological point of view these materials are quite interesting because they
      allow the use of standard photo-lithographic processes, which reduces
      significantly the time required for sensor encapsulation and membrane deposition
      and the amount of manual work required for this, all items of importance for
      sensor mass production. Problems associated with the application of this kind of
      polymers in sensors are analysed and estimation of future trends in this field of
      research are presented.

PMID- 22399989
TI  - Image-Based Airborne Sensors: A Combined Approach for Spectral Signatures
      Classification through Deterministic Simulated Annealing.
AB  - The increasing technology of high-resolution image airborne sensors, including
      those on board Unmanned Aerial Vehicles, demands automatic solutions for
      processing, either on-line or off-line, the huge amountds of image data sensed
      during the flights. The classification of natural spectral signatures in images
      is one potential application. The actual tendency in classification is oriented
      towards the combination of simple classifiers. In this paper we propose a
      combined strategy based on the Deterministic Simulated Annealing (DSA) framework.
      The simple classifiers used are the well tested supervised parametric Bayesian
      estimator and the Fuzzy Clustering. The DSA is an optimization approach, which
      minimizes an energy function. The main contribution of DSA is its ability to
      avoid local minima during the optimization process thanks to the annealing
      scheme. It outperforms simple classifiers used for the combination and some
      combined strategies, including a scheme based on the fuzzy cognitive maps and an
      optimization approach based on the Hopfield neural network paradigm.

PMID- 22399990
TI  - A Non-Intrusive GMA Welding Process Quality Monitoring System Using Acoustic
      Sensing.
AB  - Most of the inspection methods used for detection and localization of welding
      disturbances are based on the evaluation of some direct measurements of welding
      parameters. This direct measurement requires an insertion of sensors during the
      welding process which could somehow alter the behavior of the metallic
      transference. An inspection method that evaluates the GMA welding process
      evolution using a non-intrusive process sensing would allow not only the
      identification of disturbances during welding runs and thus reduce inspection
      time, but would also reduce the interference on the process caused by the direct
      sensing. In this paper a nonintrusive method for weld disturbance detection and
      localization for weld quality evaluation is demonstrated. The system is based on
      the acoustic sensing of the welding electrical arc. During repetitive tests in
      welds without disturbances, the stability acoustic parameters were calculated and
      used as comparison references for the detection and location of disturbances
      during the weld runs.

PMID- 22399991
TI  - Prediction of force measurements of a microbend sensor based on an artificial
      neural network.
AB  - Artificial neural network (ANN) based prediction of the response of a microbend
      fiber optic sensor is presented. To the best of our knowledge no similar work has
      been previously reported in the literature. Parallel corrugated plates with three
      deformation cycles, 6 mm thickness of the spacer material and 16 mm mechanical
      periodicity between deformations were used in the microbend sensor. Multilayer
      Perceptron (MLP) with different training algorithms, Radial Basis Function (RBF)
      network and General Regression Neural Network (GRNN) are used as ANN models in
      this work. All of these models can predict the sensor responses with considerable
      errors. RBF has the best performance with the smallest mean square error (MSE)
      values of training and test results. Among the MLP algorithms and GRNN the
      Levenberg-Marquardt algorithm has good results. These models successfully predict
      the sensor responses, hence ANNs can be used as useful tool in the design of more
      robust fiber optic sensors.

PMID- 22399992
TI  - Game and balance multicast architecture algorithms for sensor grid.
AB  - We propose a scheme to attain shorter multicast delay and higher efficiency in
      the data transfer of sensor grid. Our scheme, in one cluster, seeks the central
      node, calculates the space and the data weight vectors. Then we try to find a new
      vector composed by linear combination of the two old ones. We use the equal
      correlation coefficient between the new and old vectors to find the point of game
      and balance of the space and data factorsbuild a binary simple equation, seek
      linear parameters, and generate a least weight path tree. We handled the issue
      from a quantitative way instead of a qualitative way. Based on this idea, we
      considered the scheme from both the space and data factor, then we built the
      mathematic model, set up game and balance relationship and finally resolved the
      linear indexes, according to which we improved the transmission efficiency of
      sensor grid. Extended simulation results indicate that our scheme attains less
      average multicast delay and number of links used compared with other well-known
      existing schemes.

PMID- 22399993
TI  - Thick-Film Carbon Dioxide Sensor via Anodic Adsorbate Stripping Technique and Its
      Structural Dependence.
AB  - A three-electrode based CO(2) sensor was fabricated using thick-film technology.
      The performance of this sensor was further enhanced by incorporating platinum
      nanoparticles onto the working electrode surface. An eight-fold increase in the
      signal output was obtained from the electrode with the platinum nanoparticles.
      The sensing output was linearly related to the CO(2) presented. Stability
      measurements demonstrated that the decline of the active surface area and the
      sensitivity of the sensor were 8% and 13%, respectively, over a two week period
      of time. The sensor response appeared to be a structural dependence of the
      crystallographic orientation of platinum electrode.

PMID- 22399994
TI  - Sensing landscape history with an interactive location based service.
AB  - This paper introduces the STEAD approach for interpreting data acquired by a
      "human sensor", who uses an informal interactive location-based service (iLBS) to
      sense cultural-historic facts and anecdotes of, and in the landscape. This user
      generated data is collected outdoors and in situ. The approach consists of four
      related facets (who, what, where, when). Three of the four facets are discussed
      and illustrated by user generated data collected during a Dutch survey in 2008.
      These data represent the personal cultural-historic knowledge and anecdotes of
      150 people using a customized iLBS for experiencing the cultural history of a
      landscape. The "who" facet shows three dominant mentality groups (cosmopolitans,
      modern materialists and post modern hedonists) that generated user content. The
      "what" facet focuses on three subject types of pictures and four picture framing
      classes. Pictures of the place type showed to be dominant and foreground framing
      class was slightly favourite. The "where" facet is explored via density,
      distribution, and distance of the pictures made. The illustrations of the facets
      indirectly show the role of the "human sensor" with respect to the domain of
      interest. The STEAD approach needs further development of the when-facet and of
      the relations between the four facets. Finally the results of the approach may
      support data archives of iLBS applications.

PMID- 22399995
TI  - Detection and classification of human body odor using an electronic nose.
AB  - An electronic nose (E-nose) has been designed and equipped with software that can
      detect and classify human armpit body odor. An array of metal oxide sensors was
      used for detecting volatile organic compounds. The measurement circuit employs a
      voltage divider resistor to measure the sensitivity of each sensor. This E-nose
      was controlled by in-house developed software through a portable USB data
      acquisition card with a principle component analysis (PCA) algorithm implemented
      for pattern recognition and classification. Because gas sensor sensitivity in the
      detection of armpit odor samples is affected by humidity, we propose a new method
      and algorithms combining hardware/software for the correction of the humidity
      noise. After the humidity correction, the E-nose showed the capability of
      detecting human body odor and distinguishing the body odors from two persons in a
      relative manner. The E-nose is still able to recognize people, even after
      application of deodorant. In conclusion, this is the first report of the
      application of an E-nose for armpit odor recognition.

PMID- 22399996
TI  - Bistatic radar configuration for soil moisture retrieval: analysis of the spatial
      coverage.
AB  - Some outcomes of a feasibility analysis of a spaceborne bistatic radar mission
      for soil moisture retrieval are presented in this paper. The study starts from
      the orbital design of the configuration suitable for soil moisture estimation
      identified in a previous study. This configuration is refined according to the
      results of an analysis of the spatial resolution. The paper focuses on the
      assessment of the spatial coverage i.e., on the verification that an adequate
      overlap between the footprints of the antennas is ensured and on the duty cycle,
      that is the fraction of orbital period during which the bistatic data are
      acquired. A non-cooperating system is considered, in which the transmitter is the
      C-band Advanced Synthetic Aperture Radar aboard Envisat. The best performances in
      terms of duty cycle are achieved if the transmitter operates in Wide Swath Mode.
      The higher resolution Image Swath Modes that comply with the selected
      configuration have a duty cycle that is never less than 12% and can exceed 21%.
      When Envisat operates in Wide Swath Mode, the bistatic system covers a wide
      latitude range across the equator, while in some of the Image Swath Modes, the
      bistatic measurements, collected from the same orbit, cover mid-latitude areas.
      In the latter case, it might be possible to achieve full coverage in an Envisat
      orbit repeat cycle, while, for a very large latitude range such as that covered
      in Wide Swath Mode, bistatic acquisitions could be obtained over about 65% of the
      area.

PMID- 22399997
TI  - Hazardous Odor Recognition by CMAC Based Neural Networks.
AB  - Electronic noses are being developed as systems for the automated detection and
      classification of odors, vapors, and gases. Artificial neural networks (ANNs)
      have been used to analyze complex data and to recognize patterns, and have shown
      promising results in recognition of volatile compounds and odors in electronic
      nose applications. When an ANN is combined with a sensor array, the number of
      detectable chemicals is generally greater than the number of unique sensor types.
      The odor sensing system should be extended to new areas since its standard style
      where the output pattern from multiple sensors with partially overlapped
      specificity is recognized by a neural network or multivariate analysis. This
      paper describes the design, implementation and performance evaluations of the
      application developed for hazardous odor recognition using Cerebellar Model
      Articulation Controller (CMAC) based neural networks.

PMID- 22399998
TI  - Power Conservation through Energy Efficient Routing in Wireless Sensor Networks.
AB  - The power awareness issue is the primary concern within the domain of Wireless
      Sensor Networks (WSNs). Most power dissipation ocurrs during communication, thus
      routing protocols in WSNs mainly aim at power conservation. Moreover, a routing
      protocol should be scalable, so that its effectiveness does not degrade as the
      network size increases. In response to these issues, this work describes the
      development of an efficient routing protocol, named SHPER (Scaling Hierarchical
      Power Efficient Routing).

PMID- 22400000
TI  - Estimation of parameters obtained by electrochemical impedance spectroscopy on
      systems containing high capacities.
AB  - Electrochemical systems with high capacities demand devices for electrochemical
      impedance spectroscopy (EIS) with ultra-low frequencies (in order of mHz), that
      are almost impossible to accomplish with analogue techniques, but this becomes
      possible by using a computer technique and accompanying digital equipment.
      Recently, an original software and hardware for electrochemical measurements,
      intended for electrochemical systems exhibiting high capacities, such as
      supercapacitors, has been developed. One of the included methods is EIS. In this
      paper, the method of calculation of circuit parameters from an EIS curve is
      described. The results of testing on a physical model of an electrochemical
      system, constructed of known elements (including a 1.6 F capacitor) in a defined
      arrangement, proved the validity of the system and the method.

PMID- 22399999
TI  - Nanomaterial-assisted signal enhancement of hybridization for DNA biosensors: a
      review.
AB  - Detection of DNA sequences has received broad attention due to its potential
      applications in a variety of fields. As sensitivity of DNA biosensors is
      determined by signal variation of hybridization events, the signal enhancement is
      of great significance for improving the sensitivity in DNA detection, which still
      remains a great challenge. Nanomaterials, which possess some unique chemical and
      physical properties caused by nanoscale effects, provide a new opportunity for
      developing novel nanomaterial-based signal-enhancers for DNA biosensors. In this
      review, recent progress concerning this field, including some newly-developed
      signal enhancement approaches using quantum-dots, carbon nanotubes and their
      composites reported by our group and other researchers are comprehensively
      summarized. Reports on signal enhancement of DNA biosensors by non-nanomaterials,
      such as enzymes and polymer reagents, are also reviewed for comparison.
      Furthermore, the prospects for developing DNA biosensors using nanomaterials as
      signal-enhancers in future are also indicated.

PMID- 22400001
TI  - Modelling and calibration technique of laser triangulation sensors for
      integration in robot arms and articulated arm coordinate measuring machines.
AB  - A technique for intrinsic and extrinsic calibration of a laser triangulation
      sensor (LTS) integrated in an articulated arm coordinate measuring machine
      (AACMM) is presented in this paper. After applying a novel approach to the AACMM
      kinematic parameter identification problem, by means of a single calibration
      gauge object, a one-step calibration method to obtain both intrinsic-laser plane,
      CCD sensor and camera geometry-and extrinsic parameters related to the AACMM main
      frame has been developed. This allows the integration of LTS and AACMM
      mathematical models without the need of additional optimization methods after the
      prior sensor calibration, usually done in a coordinate measuring machine (CMM)
      before the assembly of the sensor in the arm. The experimental tests results for
      accuracy and repeatability show the suitable performance of this technique,
      resulting in a reliable, quick and friendly calibration method for the AACMM
      final user. The presented method is also valid for sensor integration in robot
      arms and CMMs.

PMID- 22400002
TI  - A real-time smart sensor for high-resolution frequency estimation in power
      systems.
AB  - Power quality monitoring is a theme in vogue and accurate frequency measurement
      of the power line is a major issue. This problem is particularly relevant for
      power generating systems since the generated signal must comply with restrictive
      standards. The novelty of this work is the development of a smart sensor for real
      time high-resolution frequency measurement in accordance with international
      standards for power quality monitoring. The proposed smart sensor utilizes
      commercially available current clamp, hall-effect sensor or resistor as primary
      sensor. The signal processing is carried out through the chirp z-transform.
      Simulations and experimental results show the efficiency of the proposed smart
      sensor.

PMID- 22400003
TI  - A Capacitive Humidity Sensor Based on Multi-Wall Carbon Nanotubes (MWCNTs).
AB  - A new type of capacitive humidity sensor is introduced in this paper. The sensor
      consists of two plate electrodes coated with MWCNT films and four pieces of
      isolating medium at the four corners of the sensor. According to capillary
      condensation, the capacitance signal of the sensor is sensitive to relative
      humidity (RH), which could be transformed to voltage signal by a capacitance to
      voltage converter circuit. The sensor is tested using different saturated saline
      solutions at the ambient temperature of 25  degrees C, which yielded
      approximately 11% to 97% RH, respectively. The function of the MWCNT films, the
      effect of electrode distance, the temperature character and the repeatability of
      the sensor are discussed in this paper.

PMID- 22400004
TI  - Neuro-genetic optimization of the diffuser elements for applications in a
      valveless diaphragm micropumps system.
AB  - In this study, a hybridized neuro-genetic optimization methodology realized by
      embedding numerical simulations trained artificial neural networks (ANN) into a
      genetic algorithm (GA) is used to optimize the flow rectification efficiency of
      the diffuser element for a valveless diaphragm micropump application. A higher
      efficiency ratio of the diffuser element consequently yields a higher flow rate
      for the micropump. For that purpose, optimization of the diffuser element is
      essential to determine the maximum pumping rate that the micropump is able to
      generate. Numerical simulations are initially carried out using CoventorWare(r)
      to analyze the effects of varying parameters such as diffuser angle, Reynolds
      number and aspect ratio on the volumetric flow rate of the micropump. A limited
      range of simulation results will then be used to train the neural network via
      back-propagation algorithm and optimization process commence subsequently by
      embedding the trained ANN results as a fitness function into GA. The objective of
      the optimization is to maximize the efficiency ratio of the diffuser element for
      the range of parameters investigated. The optimized efficiency ratio obtained
      from the neuro-genetic optimization is 1.38, which is higher than any of the
      maximum efficiency ratio attained from the overall parametric studies,
      establishing the superiority of the optimization method.

PMID- 22400005
TI  - A Wavelet Neural Network for SAR Image Segmentation.
AB  - This paper proposes a wavelet neural network (WNN) for SAR image segmentation by
      combining the wavelet transform and an artificial neural network. The WNN
      combines the multiscale analysis ability of the wavelet transform and the
      classification capability of the artificial neural network by setting the wavelet
      function as the transfer function of the neural network. Several SAR images are
      segmented by the network whose transfer functions are the Morlet and Mexihat
      functions, respectively. The experimental results show the proposed method is
      very effective and accurate.

PMID- 22400006
TI  - Remote-sensing image classification based on an improved probabilistic neural
      network.
AB  - This paper proposes a hybrid classifier for polarimetric SAR images. The feature
      sets consist of span image, the H/A/alpha decomposition, and the GLCM-based
      texture features. Then, a probabilistic neural network (PNN) was adopted for
      classification, and a novel algorithm proposed to enhance its performance.
      Principle component analysis (PCA) was chosen to reduce feature dimensions,
      random division to reduce the number of neurons, and Brent's search (BS) to find
      the optimal bias values. The results on San Francisco and Flevoland sites are
      compared to that using a 3-layer BPNN to demonstrate the validity of our
      algorithm in terms of confusion matrix and overall accuracy. In addition, the
      importance of each improvement of the algorithm was proven.

PMID- 22400007
TI  - Precise 3D Lug Pose Detection Sensor for Automatic Robot Welding Using a
      Structured-Light Vision System.
AB  - In this study, we propose a precise 3D lug pose detection sensor for automatic
      robot welding of a lug to a huge steel plate used in shipbuilding, where the lug
      is a handle to carry the huge steel plate. The proposed sensor consists of a
      camera and four laser line diodes, and its design parameters are determined by
      analyzing its detectable range and resolution. For the lug pose acquisition, four
      laser lines are projected on both lug and plate, and the projected lines are
      detected by the camera. For robust detection of the projected lines against the
      illumination change, the vertical threshold, thinning, Hough transform and
      separated Hough transform algorithms are successively applied to the camera
      image. The lug pose acquisition is carried out by two stages: the top view
      alignment and the side view alignment. The top view alignment is to detect the
      coarse lug pose relatively far from the lug, and the side view alignment is to
      detect the fine lug pose close to the lug. After the top view alignment, the
      robot is controlled to move close to the side of the lug for the side view
      alignment. By this way, the precise 3D lug pose can be obtained. Finally,
      experiments with the sensor prototype are carried out to verify the feasibility
      and effectiveness of the proposed sensor.

PMID- 22400008
TI  - Multi-Unmanned Aerial Vehicle (UAV) Cooperative Fault Detection Employing
      Differential Global Positioning (DGPS), Inertial and Vision Sensors.
AB  - This paper presents a method to increase the reliability of Unmanned Aerial
      Vehicle (UAV) sensor Fault Detection and Identification (FDI) in a multi-UAV
      context. Differential Global Positioning System (DGPS) and inertial sensors are
      used for sensor FDI in each UAV. The method uses additional position estimations
      that augment individual UAV FDI system. These additional estimations are obtained
      using images from the same planar scene taken from two different UAVs. Since
      accuracy and noise level of the estimation depends on several factors, dynamic
      replanning of the multi-UAV team can be used to obtain a better estimation in
      case of faults caused by slow growing errors of absolute position estimation that
      cannot be detected by using local FDI in the UAVs. Experimental results with data
      from two real UAVs are also presented.

PMID- 22400009
TI  - High Levels of Sequence Diversity in the 5' UTRs of Human-Specific L1 Elements.
AB  - Approximately 80 long interspersed element (LINE-1 or L1) copies are able to
      retrotranspose actively in the human genome, and these are termed
      retrotransposition-competent L1s. The 5' untranslated region (UTR) of the human
      specific L1 contains an internal promoter and several transcription factor
      binding sites. To better understand the effect of the L1 5' UTR on the evolution
      of human-specific L1s, we examined this population of elements, focusing on the
      sequence diversity and accumulated substitutions within their 5' UTRs. Using
      network analysis, we estimated the age of each L1 component (the 5' UTR, ORF1,
      ORF2, and 3' UTR). Through the comparison of the L1 components based on their
      estimated ages, we found that the 5' UTR of human-specific L1s accumulates
      mutations at a faster rate than the other components. To further investigate the
      L1 5' UTR, we examined the substitution frequency per nucleotide position among
      them. The results showed that the L1 5' UTRs shared relatively conserved
      transcription factor binding sites, despite their high sequence diversity. Thus,
      we suggest that the high level of sequence diversity in the 5' UTRs could be one
      of the factors controlling the number of retrotransposition-competent L1s in the
      human genome during the evolutionary battle between L1s and their host genomes.

PMID- 22400010
TI  - Differential Expression ESTs Associated with Fluorosis in Rats Liver.
AB  - The fluoride has volcanic activity and abundantly exists in environment combining
      with other elements as fluoride compounds. Recent researches indicated that the
      molecular mechanisms of intracellular fluoride toxicity were very complex.
      However, the molecular mechanisms underlying the effects on gene expression of
      chronic fluoride-induced damage is unknown, especially the detailed regulatory
      process of mitochondria. In the present study, we screened the differential
      expression ESTs associated with fluorosis by DDRT-PCR in rat liver. We gained 8
      genes, 3 new ESTs, and 1 unknown function sequence and firstly demonstrated that
      microsomal glutathione S-transferase 1 (MGST1), ATP synthase H(+) transporting
      mitochondrial F(0) complex subunit C1, selenoprotein S, mitochondrial IF1
      protein, and mitochondrial succinyl-CoA synthetase alpha subunit were
      participated in mitochondria metabolism, functional and structural damage process
      caused by chronic fluorosis. This information will be very helpful for
      understanding the molecular mechanisms of fluorosis.

PMID- 22400011
TI  - mRNA 3' end processing factors: a phylogenetic comparison.
AB  - Almost all eukaryotic mRNAs possess 3' ends with a polyadenylate (poly(A)) tail.
      This poly(A) tail is not encoded in the genome but is added by the process of
      polyadenylation. Polyadenylation is a two-step process, and this process is
      accomplished by multisubunit protein factors. Here, we comprehensively compare
      the protein machinery responsible for polyadenylation of mRNAs across many
      evolutionary divergent species, and we have found these protein factors to be
      remarkably conserved in nature. These data suggest that polyadenylation of mRNAs
      is an ancient process.

PMID- 22400013
TI  - Electrospun nanostructured fibers of collagen-biomimetic apatite on titanium
      alloy.
AB  - Titanium and its alloys are currently the mainly used materials to manufacture
      orthopaedic implants due to their excellent mechanical properties and corrosion
      resistance. Although these materials are bioinert, the improvement of biological
      properties (e.g., bone implant contact) can be obtained by the application of a
      material that mimics the bone extracellular matrix. To this aim, this work
      describes a new method to produce nanostructured collagen-apatite composites on
      titanium alloy substrate, by combining electrospinning and biomimetic
      mineralization. The characterization results showed that the obtained mineralized
      scaffolds have morphological, structural, and chemical compositional features
      similar to natural bone extracellular matrix. Finally, the topographic
      distribution of the chemical composition in the mineralized matrix evaluated by
      Fourier Transform Infrared microspectroscopy demonstrated that the apatite
      nanocrystals cover the collagen fibers assembled by the electrospinning.

PMID- 22400014
TI  - Pharmacokinetic Study of Di-Phenyl-Di-(2,4-Difluobenzohydroxamato)Tin(IV): Novel
      Metal-Based Complex with Promising Antitumor Potential.
AB  - Di-phenyl-di-(2,4-difluobenzohydroxamato)tin(IV)(DPDFT), a new metal-based
      arylhydroxamate antitumor complex, showed high in vivo and in vitro antitumor
      activity with relative low toxicity, but no data was reported regarding its
      pharmacokinetics and dependent toxicity. In this paper, a rapid, sensitive, and
      reproducible HPLC method in vivo using Diamonsil ODS column with a mixture of
      methanol and phosphoric acid in water (30 : 70, V/V, pH 3.0) as mobile phase was
      developed and validated for the determination of DPDFT. The plasma was
      deproteinized with methanol that contained acetanilide as the internal standard
      (I.S.). The photodiode array detector was set at a wavelength of 228 nm at room
      temperature and a linear curve over the concentration range 0.1~25 MUg.mL(-1) (r
      = 0.9993) was obtained. The method was used to determine the concentration-time
      profiles for DPDFT in the plasma after single intravenous administration with
      doses of 5, 10, 15 mg.kg(-1) to rats. The pharmacokinetics parameter calculations
      and modeling were carried out using the 3p97 software. The results showed that
      the concentration-time curves of DPDFT in rat plasma could be fitted to two
      compartment model.

PMID- 22400015
TI  - Hydroxyapatite coating of titanium implants using hydroprocessing and evaluation
      of their osteoconductivity.
AB  - Many techniques for the surface modification of titanium and its alloys have been
      proposed from the viewpoint of improving bioactivity. This paper contains an
      overview of surface treatment methods, including coating with hydroxyapatite
      (HAp), an osteoconductive compound. There are two types of coating methods:
      pyroprocessing and hydroprocessing. In this paper, hydroprocessing for coating on
      the titanium substrate with HAp, carbonate apatite (CO(3)-Ap), a CO(3)-Ap/CaCO(3)
      composite, HAp/collagen, and a HAp/gelatin composite is outlined. Moreover,
      evaluation by implantation of surface-modified samples in rat tibiae is
      described.

PMID- 22400016
TI  - Antifungal and antioxidant activities of pyrrolidone thiosemicarbazone complexes.
AB  - Metal complexes of (Z)-2-(pyrrolidin-2-ylidene)hydrazinecarbothioamide (L) with
      Cu(II), Co(II), and Ni(II) chlorides were tested against selected types of fungi
      and were found to have significant antifungal activities. The free-radical
      scavenging ability of the metal complexes was determined by their interaction
      with the stable free radical 2,2''-diphenyl-1-picrylhydrazyl, and all the
      compounds showed encouraging antioxidant activities. DFT calculations of the Cu
      complex were performed using molecular structures with optimized geometries.
      Molecular orbital calculations provide a detailed description of the orbitals,
      including spatial characteristics, nodal patterns, and the contributions of
      individual atoms.

PMID- 22400018
TI  - The role of adjuvant hormonal treatment after surgery for localized high-risk
      prostate cancer: results of a matched multiinstitutional analysis.
AB  - Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT)
      in high-risk prostate cancer patients (PCa) after surgery. Materials and Methods.
      The analysis case matched 172 high-risk PCa patients with positive section
      margins or non-organ confined disease and negative lymph nodes to receive
      adjuvant ADT (group 1, n = 86) or no adjuvant ADT (group 2, n = 86). Results.
      Only 11.6% of the patients died, 2.3% PCa related. Estimated 5-10-year clinical
      progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for
      group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low
      risk and T3b margins positive disease at higher risk for progression. Conclusion.
      Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer
      related death and do not need adjuvant ADT. We identified men with T3b margin
      positive disease at highest risk for clinical progression. These patients benefit
      from immediate adjuvant ADT.

PMID- 22400017
TI  - Progress in personalizing chemotherapy for bladder cancer.
AB  - Platinum-based chemotherapy is commonly used for the treatment of locally
      advanced and metastatic bladder cancer. However, there are currently no methods
      to predict chemotherapy response in this disease setting. A better understanding
      of the biology of bladder cancer has led to developments of molecular biomarkers
      that may help guide clinical decision making. These biomarkers, while promising,
      have not yet been validated in prospective trials and are not ready for clinical
      applications. As alkylating agents, platinum drugs kill cancer cells mainly
      through induction of DNA damage. A microdosing approach is currently being tested
      to determine if chemoresistance can be identified by measuring platinum-induced
      DNA damage using highly sensitive accelerator mass spectrometry technology. The
      hope is that these emerging strategies will help pave the road towards
      personalized therapy in advanced bladder cancer.

PMID- 22400019
TI  - Radical prostatectomy and intraoperative radiation therapy in high-risk prostate
      cancer.
AB  - Intraoperative electron beam radiotherapy (IOERT) for prostate cancer (PC) is a
      radiotherapeutic technique, giving high doses of radiation during radical
      prostatectomy (RP). This paper presents the published treatment approaches for
      intraoperative radiotherapy analyzing functional outcome, morbidity, and
      oncological outcome in patients with clinical intermediate-high-risk prostate
      cancer. A systematic review of the literature was performed, searching PubMed and
      Web of Science. A "free text" protocol using the term intraoperative radiotherapy
      and prostate cancer was applied. Ten records were retrieved and analyzed
      including more than 150 prostate cancer patients treated with IOERT. IOERT
      represents a feasible technique with acceptable surgical time and minimal
      toxicity. A greater number of cases and longer follow-up time are needed in order
      to assess the long-term side effects and oncological outcome.

PMID- 22400021
TI  - Lung separation in the morbidly obese patient.
AB  - Lung separation techniques in the morbidly obese patient undergoing thoracic or
      esophageal surgery may be at risk of complications during airway management.
      Access to the airway in the obese patient can be a challenge because they have
      altered airway anatomy, including a short and redundant neck, limited neck
      extension and accumulation of fat deposition in the pharyngeal wall contributing
      to difficult laryngoscopy. Securing the airway is the first priority in these
      patients followed by appropriate techniques for lung separation with the use of a
      single-lumen endotracheal tube and a bronchial blocker or another alternative is
      with the use of a double-lumen endotracheal tube. This review is focused on the
      use of lung isolation devices in the obese patient. The recommendations are based
      upon scientific evidence, case reports or personal experience. Fiberoptic
      bronchoscopy must be used to place and confirm proper placement of a single-lumen
      endotracheal tube, bronchial blocker or double-lumen endotracheal tube.

PMID- 22400020
TI  - Neurogenic bladder.
AB  - Congenital anomalies such as meningomyelocele and diseases/damage of the central,
      peripheral, or autonomic nervous systems may produce neurogenic bladder
      dysfunction, which untreated can result in progressive renal damage, adverse
      physical effects including decubiti and urinary tract infections, and
      psychological and social sequelae related to urinary incontinence. A
      comprehensive bladder-retraining program that incorporates appropriate education,
      training, medication, and surgical interventions can mitigate the adverse
      consequences of neurogenic bladder dysfunction and improve both quantity and
      quality of life. The goals of bladder retraining for neurogenic bladder
      dysfunction are prevention of urinary incontinence, urinary tract infections,
      detrusor overdistension, and progressive upper urinary tract damage due to
      chronic, excessive detrusor pressures. Understanding the physiology and
      pathophysiology of micturition is essential to select appropriate pharmacologic
      and surgical interventions to achieve these goals. Future perspectives on
      potential pharmacological, surgical, and regenerative medicine options for
      treating neurogenic bladder dysfunction are also presented.

PMID- 22400022
TI  - Perioperative glucose control in neurosurgical patients.
AB  - Many neurosurgery patients may have unrecognized diabetes or may develop stress
      related hyperglycemia in the perioperative period. Diabetes patients have a
      higher perioperative risk of complications and have longer hospital stays than
      individuals without diabetes. Maintenance of euglycemia using intensive insulin
      therapy (IIT) continues to be investigated as a therapeutic tool to decrease
      morbidity and mortality associated with derangements in glucose metabolism due to
      surgery. Suboptimal perioperative glucose control may contribute to increased
      morbidity, mortality, and aggravate concomitant illnesses. The challenge is to
      minimize the effects of metabolic derangements on surgical outcomes, reduce blood
      glucose excursions, and prevent hypoglycemia. Differences in cerebral versus
      systemic glucose metabolism, time course of cerebral response to injury, and
      heterogeneity of pathophysiology in the neurosurgical patient populations are
      important to consider in evaluating the risks and benefits of IIT. While extremes
      of glucose levels are to be avoided, there are little data to support an optimal
      blood glucose level or recommend a specific use of IIT for euglycemia maintenance
      in the perioperative management of neurosurgical patients. Individualized
      treatment should be based on the local level of blood glucose control, outpatient
      treatment regimen, presence of complications, nature of the surgical procedure,
      and type of anesthesia administered.

PMID- 22400023
TI  - Airway tube exchanger techniques in morbidly obese patients.
AB  - Morbidly obese patients may present a challenge during airway management. When
      airway tube exchange is required, it can even be more challenging than the
      primary intubation. With the increasing prevalence of morbid obesity over the
      years, there will be increasing numbers of these patients presenting for surgical
      procedures, including ones that require endotracheal tube exchanges. It is
      therefore important for anesthesiologists to be familiar with options and
      limitations of the airway tube exchanger techniques.

PMID- 22400024
TI  - Pain Management in the Elderly: An FDA Safe Use Initiative Expert Panel's View on
      Preventable Harm Associated with NSAID Therapy.
AB  - Optimization of current pain management strategies is necessary in order to
      reduce medication risks. Promoting patient and healthcare provider education on
      pain and pain medications is an essential step in reducing inadequate prescribing
      behaviors and adverse events. In an effort to raise awareness on medication
      safety, the FDA has launched the Safe Use Initiative program. The program seeks
      to identify areas with the greatest amount of preventable harm and help promote
      new methods and practices to reduce medication risks. Since the establishment of
      the program, FDA's Safe Use initiative staff convened a panel of key opinion
      leaders throughout the medical community to address pain management in older
      adults (>=65 years of age). The aim of the expert panel was to focus on areas
      where significant risk occurs and where potential interventions will be feasible,
      implementable, and lead to substantial impact. The panel suggested one focus
      could be the use of NSAIDs for pain management in the elderly.

PMID- 22400025
TI  - Alzheimer's disease and vascular deficiency: lessons from imaging studies and
      down syndrome.
AB  - Down syndrome (DS) individuals are at high risk for developing Alzheimer's
      disease (AD) and consequently provide a unique opportunity to examine the factors
      leading to the onset of AD. This paper focuses on the neglected vascular
      parallels between AD and DS that can readily be examined in DS. Several recent AD
      studies provide evidence that internal jugular vein (IJV) reflux may result in
      white matter lesions and a 30% decrease in cerebrospinal fluid (CSF) clearance of
      amyloid-beta. At the same time, studies analyzing the synthesis of amyloid-beta
      in DS showed greater than expected amounts of Abeta than would be predicted by
      the increase in gene dosage, perhaps due to slower clearance. These studies are
      discussed along with the possibility that the venous and CSF dysfunction found in
      AD patients may be present early in life in persons with DS, leaving them
      particularly vulnerable to early onset AD. Studying IJV function in DS provides
      an opportunity to understand the role of vascular function in the initiation of
      AD.

PMID- 22400026
TI  - Training experimental biologists in bioinformatics.
AB  - Bioinformatics, for its very nature, is devoted to a set of targets that
      constantly evolve. Training is probably the best response to the constant need
      for the acquisition of bioinformatics skills. It is interesting to assess the
      effects of training in the different sets of researchers that make use of it.
      While training bench experimentalists in the life sciences, we have observed
      instances of changes in their attitudes in research that, if well exploited, can
      have beneficial impacts in the dialogue with professional bioinformaticians and
      influence the conduction of the research itself.

PMID- 22400027
TI  - Systemic delivery of oncolytic viruses: hopes and hurdles.
AB  - Despite recent advances in both surgery and chemoradiotherapy, mortality rates
      for advanced cancer remain high. There is a pressing need for novel therapeutic
      strategies; one option is systemic oncolytic viral therapy. Intravenous
      administration affords the opportunity to treat both the primary tumour and any
      metastatic deposits simultaneously. Data from clinical trials have shown that
      oncolytic viruses can be systemically delivered safely with limited toxicity but
      the results are equivocal in terms of efficacy, particularly when delivered with
      adjuvant chemotherapy. A key reason for this is the rapid clearance of the
      viruses from the circulation before they reach their targets. This phenomenon is
      mainly mediated through neutralising antibodies, complement activation, antiviral
      cytokines, and tissue-resident macrophages, as well as nonspecific uptake by
      other tissues such as the lung, liver and spleen, and suboptimal viral escape
      from the vascular compartment. A range of methods have been reported in the
      literature, which are designed to overcome these hurdles in preclinical models.
      In this paper, the potential advantages of, and obstacles to, successful systemic
      delivery of oncolytic viruses are discussed. The next stage of development will
      be the commencement of clinical trials combining these novel approaches for
      overcoming the barriers with systemically delivered oncolytic viruses.

PMID- 22400028
TI  - Microenvironment-centred dynamics in aggressive B-cell lymphomas.
AB  - Aggressive B-cell lymphomas share high proliferative and invasive attitudes and
      dismal prognosis despite heterogeneous biological features. In the interchained
      sequence of events leading to cancer progression, neoplastic clone-intrinsic
      molecular events play a major role. Nevertheless, microenvironment-related cues
      have progressively come into focus as true determinants for this process. The
      cancer-associated microenvironment is a complex network of nonneoplastic immune
      and stromal cells embedded in extracellular components, giving rise to a
      multifarious crosstalk with neoplastic cells towards the induction of a
      supportive milieu. The immunological and stromal microenvironments have been
      classically regarded as essential partners of indolent lymphomas, while
      considered mainly negligible in the setting of aggressive B-cell lymphomas that,
      by their nature, are less reliant on external stimuli. By this paper we try to
      delineate the cardinal microenvironment-centred dynamics exerting an influence
      over lymphoid clone progression in aggressive B-cell lymphomas.

PMID- 22400029
TI  - Marrow Stromal Cell Infusion Rescues Hematopoiesis in Lethally Irradiated Mice
      despite Rapid Clearance after Infusion.
AB  - Marrow stromal cells (MSCs, also termed mesenchymal stem cells) have been
      proposed as a promising cellular therapy for tissue injury including radiation
      induced marrow failure, but evidence for a direct effect is lacking. To assess
      the effects of MSCs on survival after lethal irradiation, we infused syngeneic
      MSCs (either as immortalized MSCs clones or primary MSCs) intravenously into wild
      type C57/Bl6 mice within 24 hours of lethal total body irradiation (TBI). Mice
      receiving either of the MSC preparations had significantly improved survival when
      compared to controls. In vivo imaging, immune histochemistry, and RT-PCR employed
      to detect MSCs indicated that the infused MSCs were predominantly localized to
      the lungs and rapidly cleared following infusion. Our results suggest that a
      single infusion of MSCs can improve survival after otherwise lethal TBI but the
      effect is not due to a direct interaction with, or contribution to, the damaged
      marrow by MSCs.

PMID- 22400030
TI  - AIDS-Related Non-Hodgkin's Lymphoma in the Era of Highly Active Antiretroviral
      Therapy.
AB  - In economically developed countries, AIDS-related lymphoma (ARL) accounts for a
      large proportion of malignances in HIV-infected individuals. Since the
      introduction of highly active anti-retroviral therapy (HAART) in 1996,
      epidemiology and prognosis of ARL have changed. While there is a slight increase
      in the incidence of Hodgkin's lymphoma in HIV-infected individuals, use of HAART
      has contributed to a decline in the incidence of non-Hodgkin's lymphoma (NHL) and
      also a decrease in the overall incidence of ARL. Strategies that employ HAART,
      improved supportive care, and the use of Rituximab with multi-agent chemotherapy
      have contributed to improved rates of complete remission and survival of patients
      with ARL that rival those seen in stage and histology matched HIV negative NHL
      patients. Most recent clinical trials demonstrate better outcomes with the use of
      rituximab in ARL. Tumor histogenesis (germinal center vs. non-germinal center
      origin) is associated with lymphoma-specific outcomes in the setting of AIDS
      related diffuse-large B cell lymphoma. High-dose chemotherapy (HDCT) and
      autologous stem cell rescue (ASCT) can be effective for a subset of patients with
      relapsed ARL. HIV sero-status alone should not preclude consideration of ASCT in
      the setting of ARL relapse. Clinical trials investigating the role of allogeneic
      hematopoietic stem cell transplant in ARL are currently underway.

PMID- 22400031
TI  - JAK2 Inhibition: Reviewing a New Therapeutical Option in Myeloproliferative
      Neoplasms.
AB  - JAK2 is a tyrosine kinase gene that plays an essential role in the development of
      normal haematopoiesis. Hyperactivation of JAK2 occurs in myeloproliferative
      neoplasms by different mechanisms. As a consequence, JAK2 inhibitors have been
      designed to suppress the cytokine signalling cascade caused by the constitutive
      activation of JAK2. In clinical trials, JAK2 inhibitors are efficient in
      decreasing spleen size, controlling clinical symptoms, and improving quality of
      life in patients with myeloproliferative neoplasms. However, JAK2 inhibitors are
      unable to target uncommitted hematopoietic progenitors responsible of the
      initiation of the myeloproliferative disease. It is expected that, in order to
      cure the myeloproliferative disease, JAK2 inhibitors should be combined with
      other drugs to target simultaneously different pathways and to target the
      initiator hematopoietic cell population in myeloproliferative disorders. Taking
      advantage of the inhibition of the cytokine cascade of JAK2 inhibitors, these
      compounds are going to be used not only to treat patients with hematological
      neoplasms but may also be beneficial to treat patients with rheumatoid arthritis
      or other inflammatory diseases.

PMID- 22400032
TI  - Murine models of B-cell lymphomas: promising tools for designing cancer
      therapies.
AB  - Human B-cell lymphomas, the fourth most common hematologic malignancy, are
      currently the subject of extensive research. The limited accessibility of
      biopsies, the heterogeneity among patients, and the subtypes of lymphomas have
      necessitated the development of animal models to decipher immune escape
      mechanisms and design new therapies. Here, we summarize the cell lines and murine
      models used to study lymphomagenesis, the lymphoma microenvironment, and the
      efficacy of new therapies. These data allow us to understand the role of the
      immune system in the fight against tumors. Exploring the advantages and
      limitations of immunocompetent versus immunodeficient models improves our
      understanding of the molecular and cellular mechanisms of tumor genesis and
      development as well as the fundamental processes governing the interaction of
      tumors and their host tissues. We posit that these basic preclinical
      investigations will open up new and promising approaches to designing better
      therapies.

PMID- 22400033
TI  - Phenotypical and functional analysis of intraepithelial lymphocytes from small
      intestine of mice in oral tolerance.
AB  - In this work, we evaluated the effects of administration of OVA on phenotype and
      function of intraepithelial lymphocytes (IELs) from small intestine of transgenic
      (TGN) DO11.10 and wild-type BALB/c mice. While the small intestines from BALB/c
      presented a well preserved structure, those from TGN showed an inflamed aspect.
      The ingestion of OVA induced a reduction in the number of IELs in small
      intestines of TGN, but it did not change the frequencies of CD8(+) and CD4(+) T
      cell subsets. Administration of OVA via oral + ip increased the frequency of
      CD103(+) cells in CD4(+) T-cell subset in IELs of both BALB/c and TGN mice and
      elevated its expression in CD8beta(+) T-cell subset in IELs of TGN. The frequency
      of Foxp3(+) cells increased in all subsets in IELs of BALB/c treated with OVA; in
      IELs of TGN, it increased only in CD25(+) subset. IELs from BALB/c tolerant mice
      had lower expression of all cytokines studied, whereas those from TGN showed high
      expression of inflammatory cytokines, especially of IFN-gamma, TGF-beta, and TNF
      alpha. Overall, our results suggest that the inability of TGN to become tolerant
      may be related to disorganization and altered proportions of
      inflammatory/regulatory T cells in its intestinal mucosa.

PMID- 22400034
TI  - Contribution of the infection-associated complement regulator-acquiring surface
      protein 4 (ErpC) to complement resistance of Borrelia burgdorferi.
AB  - Borrelia burgdorferi evades complement-mediated killing by interacting with
      complement regulators through distinct complement regulator-acquiring surface
      proteins (CRASPs). Here, we extend our analyses to the contribution of CRASP-4 in
      mediating complement resistance of B. burgdorferi and its interaction with human
      complement regulators. CRASP-4 (also known as ErpC) was immobilized onto magnetic
      beads and used to capture proteins from human serum. Following Western blotting,
      factor H (CFH), CFH-related protein 1 (CFHR1), CFHR2, and CFHR5 were identified
      as ligands of CRASP-4. To analyze the impact of native CRASP-4 on mediating
      survival of serum-sensitive cells in human serum, a B. garinii strain was
      generated that ectopically expresses CRASP-4. CRASP-4-producing bacteria bound
      CFHR1, CFHR2, and CFHR5 but not CFH. In addition, transformed spirochetes
      deposited significant amounts of lethal complement components on their surface
      and were susceptible to human serum, thus indicating that CRASP-4 plays a
      subordinate role in complement resistance of B. burgdorferi.

PMID- 22400036
TI  - Serum cytokine profile by ELISA in patients with echinococcal cysts of the liver:
      a stage-specific approach to assess their biological activity.
AB  - To investigate the usefulness of serum cytokine dosage in the clinical management
      of cystic echinococcosis (CE), we analyzed serum levels of Th1 and Th2 cytokines
      in patients with hepatic CE in different cyst stages, CE1-2 (active), CE3a-3b
      (transitional), and CE4-5 (inactive). Ex vivo assessment of Th1 (IFN-gamma) and
      Th2 (IL-4, IL-13, and IL-10) cytokines in sera was carried out using ELISA. IL-10
      was undetectable in all serum samples of patients and controls, while a few sera
      contained measurable amounts of IFN-gamma, IL-4, and IL-13. No statistically
      significant difference was found between the percentages of positive samples for
      each cytokine and the different groups analyzed (patients/controls, stage,
      number, location, and size of the cyst, serology, and sex of patients), with the
      exception of the association of IL-4 and IL-13 with the cyst stage. Overall, this
      investigation showed many limits of serum cytokine dosage as a marker of
      biological activity of echinococcal cysts. Because of low sensitivity and lack of
      specificity of this test, we believe that other ways to evaluate ex vivo
      biological activity of the cysts should be explored.

PMID- 22400037
TI  - New insights into the immunological changes in IL-10-deficient mice during the
      course of spontaneous inflammation in the gut mucosa.
AB  - IL-10 is a regulatory cytokine that plays a major role in the homeostasis of the
      gut and this is illustrated by the fact that IL-10(-/-) mice develop spontaneous
      colitis. In this study, IL-10(-/-) mice were analyzed for immunological changes
      during colitis development. We found a reduced frequency of regulatory T cells
      CD4(+)CD25(+)Foxp3(+) and higher frequency of activated T cells in the colon that
      precedes the macroscopic signs of the disease. Production of IL-17 and IFN-gamma
      was higher in the colon. Colitis progression culminates with the reduction of
      CD4(+)LAP(+) regulatory T cells in the intestine. Frequency of B1 cells and the
      secretory IgA production were both elevated. Despite these alterations, 16-week
      old IL-10(-/-) mice could be rendered tolerant by a continuous feeding protocol.
      Our study provides detailed analysis of changes that precede colitis and it also
      suggests that oral tolerance could be used to design novel alternative therapies
      for the disease.

PMID- 22400035
TI  - Toxin-based targeted therapy for malignant brain tumors.
AB  - Despite advances in conventional treatment modalities for malignant brain tumors
      surgery, radiotherapy, and chemotherapy-the prognosis for patients with high
      grade astrocytic tumor remains dismal. The highly heterogeneous and diffuse
      nature of astrocytic tumors calls for the development of novel therapies.
      Advances in genomic and proteomic research indicate that treatment of brain tumor
      patients can be increasingly personalized according to the characteristics of the
      targeted tumor and its environment. Consequently, during the last two decades, a
      novel class of investigative drug candidates for the treatment of central nervous
      system neoplasia has emerged: recombinant fusion protein conjugates armed with
      cytotoxic agents targeting tumor-specific antigens. The clinical applicability of
      the tumor-antigen-directed cytotoxic proteins as a safe and viable therapy for
      brain tumors is being investigated. Thus far, results from ongoing clinical
      trials are encouraging, as disease stabilization and patient survival
      prolongation have been observed in at least 109 cases. This paper summarizes the
      major findings pertaining to treatment with the different antiglioma cytotoxins
      at the preclinical and clinical stages.

PMID- 22400038
TI  - TCR gene transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 epitopes as melanoma
      specific immune targets.
AB  - Adoptive therapy with TCR gene-engineered T cells provides an attractive and
      feasible treatment option for cancer patients. Further development of TCR gene
      therapy requires the implementation of T-cell target epitopes that prevent "on
      target" reactivity towards healthy tissues and at the same time direct a
      clinically effective response towards tumor tissues. Candidate epitopes that meet
      these criteria are MAGE-C2(336-344)/HLA-A2 (MC2/A2) and MAGE-A3(243-258)/HLA-DP4
      (MA3/DP4). We molecularly characterized TCRalphabeta genes of an MC2/A2-specific
      CD8 and MA3/DP4-specific CD4 T-cell clone derived from melanoma patients who
      responded clinically to MAGE vaccination. We identified MC2/A2 and MA3/DP4
      specific TCR-Valpha3/Vbeta28 and TCR-Valpha38/Vbeta2 chains and validated these
      TCRs in vitro upon gene transfer into primary human T cells. The MC2 and MA3 TCR
      were surface-expressed and mediated CD8 T-cell functions towards melanoma cell
      lines and CD4 T-cell functions towards dendritic cells, respectively. We intend
      to start testing these MAGE-specific TCRs in phase I clinical trial.

PMID- 22400039
TI  - Antigen-specific T cells and cytokines detection as useful tool for understanding
      immunity against zoonotic infections.
AB  - Zoonoses include a broad range of diseases, that are becoming of great interest,
      due to the climate changing, that cause the adaptation of vectors to new niches
      and environments. Host immune responses play a crucial role in determining the
      outcome of infections, as documented by expansion of antigen-specific T cells
      during several zoonotic infections. Thus, understanding of the contribution of
      antigen-specific T-cell subsets in the host immune response is a powerful tool to
      evaluate the different immunological mechanisms involved in zoonotic infections
      and for the development of effective vaccines. In this paper we discuss the role
      of T cells in some eukaryotic and prokaryotic infectious models.

PMID- 22400041
TI  - Inhibition of arterial allograft intimal hyperplasia using recipient dendritic
      cells pretreated with B7 antisense peptide.
AB  - BACKGROUND: Low expression or absence of dendritic cell (DC) surface B7 molecules
      can induce immune tolerance or hyporesponse. Whether DCs could induce indirect
      allogeneic-specific cross-tolerance or hyporesponse to recipient T cells remains
      unclear. METHODS: Generated from C3H/He mice bone marrow cells pulsed with donor
      antigen from C57BL/6 mice, recipient DCs were incubated with B7 antisense peptide
      (B7AP). Immune regulatory activities were examined in vitro by a series of mixed
      lymphocyte reactions. Murine allogeneic carotid artery orthotopic transplantation
      was performed from C57BL/6 to C3H/He. Recipients were given B7AP-treated DCs 7
      days before transplantation. Allograft pathological analysis was done 2 months
      after transplantation. RESULTS: B7AP-pretreated DCs markedly inhibited T-cell
      proliferation compared with untreated group. Pretreated T cells exhibited
      markedly reduced response to alloantigen versus third-party antigen. Pathological
      analysis of arterial allografts demonstrated significant reduction of intimal
      hyperplasia in B7-AP pretreated group versus control. CONCLUSION: Blockade of B7
      molecules by B7AP could induce indirect allogeneic-specific hyporesponse and
      inhibit arterial allograft intimal hyperplasia, which may be involved in future
      strategies for human allograft chronic rejection.

PMID- 22400042
TI  - Role of in vitro stimulation with lipopolysaccharide on T-cell activation in HIV
      infected antiretroviral-treated patients.
AB  - We investigated the effect of LPS in vitro stimulation on T-cell activation in
      HIV-infected patients with different CD4+ recovery on HAART. PBMCs from 30 HIV
      positive, HAART-treated, aviremic individuals with different CD4+ reconstitution
      (Low Responders: CD4+ < 350/MUL; Intermediate Responders: CD4+ 350-599/MUL; High
      Responders: CD4+ >= 600/MUL) were cultured with LPS and the proportion of HLA
      DR/CD38- and Ki67-expressing CD4+/CD8+ T-cells was measured (flow cytometry).
      Upon LPS stimulation, significantly higher CD4+ and CD8+HLA-DR+ cells were shown
      in LR and IR versus HIV-negative controls. While no differences in the proportion
      of LPS-stimulated CD4+CD38+ cells were recorded amongst HIV-positive subgroups,
      CD8+CD38+ cells were more elevated in patients with lower CD4+ recovery on HAART
      (i.e., LR and IR). Upon in vitro LPS stimulation, HLA-DR and CD38 expression on T
      cells are differentially regulated. While HLA-DR induction reflects impaired CD4+
      reconstitution on HAART, cell-surface CD38 expression is increased only on CD8+ T
      cells, allowing to speculate that the sole induction of CD38 on CD4+ cells may
      not be sufficient to depict LPS-driven immune activation in HIV.

PMID- 22400040
TI  - Cytotoxic chemotherapy and CD4+ effector T cells: an emerging alliance for
      durable antitumor effects.
AB  - Standard cytotoxic chemotherapy can initially achieve high response rates, but
      relapses often occur in patients and represent a severe clinical problem. As
      increasing numbers of chemotherapeutic agents are found to have immunostimulatory
      effects, there is a growing interest to combine chemotherapy and immunotherapy
      for synergistic antitumor effects and improved clinical benefits. Findings from
      recent studies suggest that highly activated, polyfunctional CD4+ effector T
      cells have tremendous potential in strengthening and sustaining the overall host
      antitumor immunity in the postchemotherapy window. This review focuses on the
      latest progresses regarding the impact of chemotherapy on CD4+ T-cell phenotype
      and function and discusses the prospect of exploiting CD4+ T cells to control
      tumor progression and prevent relapse after chemotherapy.

PMID- 22400043
TI  - Perinatal programming of childhood asthma: early fetal size, growth trajectory
      during infancy, and childhood asthma outcomes.
AB  - The "fetal origins hypothesis" or concept of "developmental programming" suggests
      that faltering fetal growth and subsequent catch-up growth are implicated in the
      aetiology of cardiovascular disease. Associations between reduced birth weight,
      rapid postnatal weight gain, and asthma suggest that there are fetal origins to
      respiratory disease. The present paper first summarises the literature relating
      birth weight and post natal growth trajectories to asthma outcomes. Second,
      issues regarding the interpretation of antenatal fetal ultrasound measurements
      are discussed. Finally, recent reports linking antenatal measurement and growth
      trajectory to early childhood asthma outcomes are discussed. Understanding the
      nature and timing of factors which influence antenatal growth may give important
      insight into the antecedents of early-onset asthma with implications for
      interventions.

PMID- 22400045
TI  - A finite element study of micropipette aspiration of single cells: effect of
      compressibility.
AB  - Micropipette aspiration (MA) technique has been widely used to measure the
      viscoelastic properties of different cell types. Cells experience nonlinear large
      deformations during the aspiration procedure. Neo-Hookean viscohyperelastic
      (NHVH) incompressible and compressible models were used to simulate the creep
      behavior of cells in MA, particularly accounting for the effect of
      compressibility, bulk relaxation, and hardening phenomena under large strain. In
      order to find optimal material parameters, the models were fitted to the
      experimental data available for mesenchymal stem cells. Finally, through Neo
      Hookean porohyperelastic (NHPH) material model for the cell, the influence of
      fluid flow on the aspiration length of the cell was studied. Based on the
      results, we suggest that the compressibility and bulk relaxation/fluid flow play
      a significant role in the deformation behavior of single cells and should be
      taken into account in the analysis of the mechanics of cells.

PMID- 22400044
TI  - Advances in the discovery and development of heat-shock protein 90 inhibitors for
      cancer treatment.
AB  - INTRODUCTION: Over the last 15 - 20 years, targeted anticancer strategies have
      focused on therapies aimed at abrogating a single malignant protein. Agents that
      are directed towards the inhibition of a single oncoprotein have resulted in a
      number of useful drugs in the treatment of cancers (i.e., Gleevec, BCR-ABL;
      Tarceva and Iressa, EGFR). However, such a strategy relies on the notion that a
      cancer cell is dependent on a single signaling pathway for its survival. The
      possibility that a cancer cell may mutate or switch its dependence to another
      signaling pathway can result in the ineffectiveness of such agents. Recent
      advances in the biology of heat-shock protein 90 (Hsp90) have revealed intimate
      details into the complexity of the chaperoning process that Hsp90 is engaged in
      and, at the same time, have offered those involved in drug discovery several
      unique ways to interfere in this process.  AREAS COVERED: This review provides
      the current understanding of the chaperone cycle of Hsp90 and presents the
      multifaceted approaches used by researchers in the discovery of potential Hsp90
      drugs. It discusses the phenotypic outcomes in cancer cells on Hsp90 inhibition
      by these several approaches and also addresses several distinctions observed
      among direct Hsp90 ATP-pocket competitors providing commentary on the potential
      biological outcomes as well as the clinical relevance of such features.  EXPERT
      OPINION: The significantly different phenotypic outcomes observed from Hsp90
      inhibition by the many inhibitors developed suggest that the clinical development
      of Hsp90 inhibitors would be better served by careful consideration of the
      pharmacokinetic/pharmacodynamic properties of individual candidates rather than a
      generic approach directed towards the target.

PMID- 22400046
TI  - Higher-order spectrum in understanding nonlinearity in EEG rhythms.
AB  - The fundamental nature of the brain's electrical activities recorded as
      electroencephalogram (EEG) remains unknown. Linear stochastic models and spectral
      estimates are the most common methods for the analysis of EEG because of their
      robustness, simplicity of interpretation, and apparent association with rhythmic
      behavioral patterns in nature. In this paper, we extend the use of higher-order
      spectrum in order to indicate the hidden characteristics of EEG signals that
      simply do not arise from random processes. The higher-order spectrum is an
      extension Fourier spectrum that uses higher moments for spectral estimates. This
      essentially nullifies all Gaussian random effects, therefore, can reveal non
      Gaussian and nonlinear characteristics in the complex patterns of EEG time
      series. The paper demonstrates the distinguishing features of bispectral analysis
      for chaotic systems, filtered noises, and normal background EEG activity. The
      bispectrum analysis detects nonlinear interactions; however, it does not quantify
      the coupling strength. The squared bicoherence in the nonredundant region has
      been estimated to demonstrate nonlinear coupling. The bicoherence values are
      minimal for white Gaussian noises (WGNs) and filtered noises. Higher bicoherence
      values in chaotic time series and normal background EEG activities are indicative
      of nonlinear coupling in these systems. The paper shows utility of bispectral
      methods as an analytical tool in understanding neural process underlying human
      EEG patterns.

PMID- 22400047
TI  - Linear and nonlinear heart rate variability indexes in clinical practice.
AB  - Biological organisms have intrinsic control systems that act in response to
      internal and external stimuli maintaining homeostasis. Human heart rate is not
      regular and varies in time and such variability, also known as heart rate
      variability (HRV), is not random. HRV depends upon organism's physiologic and/or
      pathologic state. Physicians are always interested in predicting patient's risk
      of developing major and life-threatening complications. Understanding biological
      signals behavior helps to characterize patient's state and might represent a step
      toward a better care. The main advantage of signals such as HRV indexes is that
      it can be calculated in real time in noninvasive manner, while all current
      biomarkers used in clinical practice are discrete and imply blood sample
      analysis. In this paper HRV linear and nonlinear indexes are reviewed and data
      from real patients are provided to show how these indexes might be used in
      clinical practice.

PMID- 22400048
TI  - Characteristics of evoked potential multiple EEG recordings in patients with
      chronic pain by means of parallel factor analysis.
AB  - This paper presents an alternative method, called as parallel factor analysis
      (PARAFAC) with a continuous wavelet transform, to analyze of brain activity in
      patients with chronic pain in the time-frequency-channel domain and quantifies
      differences between chronic pain patients and controls in these domains. The
      event related multiple EEG recordings of the chronic pain patients and non-pain
      controls with somatosensory stimuli (pain, random pain, touch, random touch) are
      analyzed. Multiple linear regression (MLR) is applied to describe the effects of
      aging on the frequency response differences between patients and controls. The
      results show that the somatosensory cortical responses occurred around 250 ms in
      both groups. In the frequency domain, the neural response frequency in the pain
      group (around 4 Hz) was less than that in the control group (around 5.5 Hz) under
      the somatosensory stimuli. In the channel domain, cortical activation was
      predominant in the frontal region for the chronic pain group and in the central
      region for controls. The indices of active ratios were statistical significant
      between the two groups in the frontal and central regions. These findings
      demonstrate that the PARAFAC is an interesting method to understanding the
      pathophysiological characteristics of chronic pain.

PMID- 22400049
TI  - Modeling the spatial distribution of chronic tumor hypoxia: implications for
      experimental and clinical studies.
AB  - Tumor oxygenation status is considered one of the important prognostic markers in
      cancer since it strongly influences the response of cancer cells to various
      treatments; in particular, to radiation therapy. Thus, a proper and accurate
      assessment of tumor oxygen distribution before the treatment may highly affect
      the outcome of the treatment. The heterogeneous nature of tumor hypoxia, mainly
      influenced by the complex tumor microenvironment, often makes its quantification
      very difficult. The usual methods used to measure tumor hypoxia are biomarkers
      and the polarographic needle electrode. Although these techniques may provide an
      acceptable assessment of hypoxia, they are invasive and may not always give a
      spatial distribution of hypoxia, which is very useful for treatment planning. An
      alternative method to quantify the tumor hypoxia is to use theoretical
      simulations with the knowledge of tumor vasculature. The purpose of this paper is
      to model tumor hypoxia using a known spatial distribution of tumor vasculature
      obtained from image data, to analyze the accuracy of polarographic needle
      electrode measurements in quantifying hypoxia, to quantify the optimum number of
      measurements required to satisfactorily evaluate the tumor oxygenation status,
      and to study the effects of hypoxia on radiation response. Our results indicate
      that the model successfully generated an accurate oxygenation map for tumor cross
      sections with known vascular distribution. The method developed here provides a
      way to estimate tumor hypoxia and provides guidance in planning accurate and
      effective therapeutic strategies and invasive estimation techniques. Our results
      agree with the previous findings that the needle electrode technique gives a good
      estimate of tumor hypoxia if the sampling is done in a uniform way with 5-6
      tracks of 20-30 measurements each. Moreover, the analysis indicates that the
      accurate measurement of oxygen profile can be very useful in determining right
      radiation doses to the patients.

PMID- 22400050
TI  - A batch rival penalized expectation-maximization algorithm for Gaussian mixture
      clustering with automatic model selection.
AB  - Within the learning framework of maximum weighted likelihood (MWL) proposed by
      Cheung, 2004 and 2005, this paper will develop a batch Rival Penalized
      Expectation-Maximization (RPEM) algorithm for density mixture clustering provided
      that all observations are available before the learning process. Compared to the
      adaptive RPEM algorithm in Cheung, 2004 and 2005, this batch RPEM need not assign
      the learning rate analogous to the Expectation-Maximization (EM) algorithm
      (Dempster et al., 1977), but still preserves the capability of automatic model
      selection. Further, the convergence speed of this batch RPEM is faster than the
      EM and the adaptive RPEM in general. The experiments show the superior
      performance of the proposed algorithm on the synthetic data and color image
      segmentation.

PMID- 22400051
TI  - Computational fluid dynamics analysis of the effect of plaques in the left
      coronary artery.
AB  - This study was to investigate the hemodynamic effect of simulated plaques in left
      coronary artery models, which were generated from a sample patient's data.
      Plaques were simulated and placed at the left main stem and the left anterior
      descending (LAD) to produce at least 60% coronary stenosis. Computational fluid
      dynamics analysis was performed to simulate realistic physiological conditions
      that reflect the in vivo cardiac hemodynamics, and comparison of wall shear
      stress (WSS) between Newtonian and non-Newtonian fluid models was performed. The
      pressure gradient (PSG) and flow velocities in the left coronary artery were
      measured and compared in the left coronary models with and without presence of
      plaques during cardiac cycle. Our results showed that the highest PSG was
      observed in stenotic regions caused by the plaques. Low flow velocity areas were
      found at postplaque locations in the left circumflex, LAD, and bifurcation. WSS
      at the stenotic locations was similar between the non-Newtonian and Newtonian
      models although some more details were observed with non-Newtonian model. There
      is a direct correlation between coronary plaques and subsequent hemodynamic
      changes, based on the simulation of plaques in the realistic coronary models.

PMID- 22400052
TI  - Multiscale autoregressive identification of neuroelectrophysiological systems.
AB  - Electrical signals between connected neural nuclei are difficult to model because
      of the complexity and high number of paths within the brain. Simple parametric
      models are therefore often used. A multiscale version of the autoregressive with
      exogenous input (MS-ARX) model has recently been developed which allows selection
      of the optimal amount of filtering and decimation depending on the signal-to
      noise ratio and degree of predictability. In this paper, we apply the MS-ARX
      model to cortical electroencephalograms and subthalamic local field potentials
      simultaneously recorded from anesthetized rodent brains. We demonstrate that the
      MS-ARX model produces better predictions than traditional ARX modeling. We also
      adapt the MS-ARX results to show differences in internuclei predictability
      between normal rats and rats with 6OHDA-induced parkinsonism, indicating that
      this method may have broad applicability to other neuroelectrophysiological
      studies.

PMID- 22400053
TI  - Solid dynamic models for analysis of stress and strain in human hearts.
AB  - This paper proposes a solid model based on four-dimensional trivariate B-spline
      for strain and stress analysis of ventricular myocardium. With a series of
      processing steps in the four-dimensional medical images, the feature points of
      ventricular inner and outer wall are obtained. A B-spline surface is then used to
      build the dynamic deformation model of the myocardial walls. With such a surface
      model, a hexahedron control mesh can be constructed by sweeping the cloud data,
      and the ventricular solid model is built by fitting the trivariate B-spline
      parameters. Based on these models, a method of isogeometric analysis can be
      applied to calculate the stress and strain continuously distributed in the
      ventricle. The model is represented smoothly in the cylindrical coordinate system
      and is easy to measure myocardium dynamics for finding abnormal motion.
      Experiments are carried out for comparing the stress and strain distribution. It
      is found that the solid model can determine ventricular dynamics which can well
      reflect the deformation distribution in the heart and imply early clues of
      cardiac diseases.

PMID- 22400054
TI  - Principal component analysis of gait kinematics data in acute and chronic stroke
      patients.
AB  - We present the joint angles analysis by means of the principal component analysis
      (PCA). The data from twenty-seven acute and chronic hemiplegic patients were used
      and compared with data from five healthy subjects. The data were collected during
      walking along a 10-meter long path. The PCA was applied on a data set consisting
      of hip, knee, and ankle joint angles of the paretic and the nonparetic leg. The
      results point to significant differences in joint synergies between the acute and
      chronic hemiplegic patients that are not revealed when applying typical methods
      for gait assessment (clinical scores, gait speed, and gait symmetry). The results
      suggest that the PCA allows classification of the origin for the deficit in the
      gait when compared to healthy subjects; hence, the most appropriate treatment can
      be applied in the rehabilitation.

PMID- 22400055
TI  - Finite element modelling of pulsatile blood flow in idealized model of human
      aortic arch: study of hypotension and hypertension.
AB  - A three-dimensional computer model of human aortic arch with three branches is
      reproduced to study the pulsatile blood flow with Finite Element Method. In
      specific, the focus is on variation of wall shear stress, which plays an
      important role in the localization and development of atherosclerotic plaques.
      Pulsatile pressure pulse is used as boundary condition to avoid flow entry
      development, and the aorta walls are considered rigid. The aorta model along with
      boundary conditions is altered to study the effect of hypotension and
      hypertension. The results illustrated low and fluctuating shear stress at outer
      and inner wall of aortic arch, proximal wall of branches, and entry region.
      Despite the simplification of aorta model, rigid walls and other assumptions
      results displayed that hypertension causes lowered local wall shear stresses. It
      is the sign of an increased risk of atherosclerosis. The assessment of
      hemodynamics shows that under the flow regimes of hypotension and hypertension,
      the risk of atherosclerosis localization in human aorta may increase.

PMID- 22400056
TI  - Restrictive cardiomyopathy in inherited ATTR amyloidosis (TTR-Ser23Asn) in a
      patient of German-Italian extraction.
AB  - Amyloidosis occurs when certain soluble proteins are transformed into amyloid
      fibrils in the extracellular space. Most common are the light-chain amyloidoses;
      less common is the AA-amyloidosis, which follows chronic inflammatory diseases,
      and the amyloidoses of transthyretin (TTR) origin. We report on a women of
      Italian-German origin with the mutation TTR (Ser23Asn). Whole body scintigraphy
      using TC99m-DPD showed end stage hereditary amyloidosis caused by ATTR with
      predominant tracer retention in the myocardium. Myocardial biopsies revealed the
      presence of amyloid by Congo red staining. Further immunohistochemical analysis
      showed ATTR amyloidosis. DNA sequencing revealed a point mutation of the
      transthyretin gene leading to a single amino acid substitution. The only
      effective treatment in patients with manifest cardiac ATTR amyloidosis is
      combined heart and liver transplantation. Our patient was placed on a list for
      this procedure, but unfortunately she died during the standby procedure due to
      urosepsis.

PMID- 22400057
TI  - Dynamic renogram with 99mTc DTPA in patient with adult polycystic kidney disease.

PMID- 22400058
TI  - A rare case of adult primary jejunal volvulus.
AB  - Jejunal volvulus is a rare and life threatening presentation of intestinal
      ischaemia. Clinical features, laboratory investigations and plain abdominal films
      are non-specific and so computed tomography (CT) scanning is useful in reaching a
      timely diagnosis. Rapid recourse to surgical intervention is typical and life
      saving. We report a rare case of primary jejunal volvulus which, after diagnosis
      on emergency CT scanning, was successfully treated by laparotomy and resection of
      infarcted bowel.

PMID- 22400059
TI  - Can gout mimic a soft tissue tumour?
AB  - Gout is a disease where an abnormal collection of uric crystals (gouty tophi) can
      often be found in the foot and ankle. Occasionally such tophies are found at
      unusual sites and this can pose a challenge to the clinician where diagnosis and
      treatment is concerned. We describe a patient who presented to our oncology
      department with a swelling on his right thigh which was clinically diagnosed to
      be a soft tissue sarcoma, but after further investigations it turned out to be a
      gouty tophi. The purpose of this case report is to emphasise the variable
      presentation of gout and the challenges that can be faced by clinicians in
      diagnosing a soft tissue swelling.

PMID- 22400060
TI  - Multiple facets of PHACE(S).

PMID- 22400061
TI  - Protease activity: meeting its theranostic potential.
AB  - This themed issue provides up-to-date review and research articles covering the
      theranostic applications in the combined fields of protease research, diagnostics
      and drug development.

PMID- 22400062
TI  - Theranostic Imaging of the Kinases and Proteases that Modulate Cell Death and
      Survival.
AB  - Several signaling cascades are involved in cell death, with a significant amount
      of crosstalk between them. Despite the complexity of these cascades several key
      pro-survival and pro-death players have been identified. These include PI3
      kinase, AKT and caspase-3. Here we review the approaches used to date to perform
      molecular imaging of these important targets. We focus in particular on
      approaches that include the possibility of modulating the activity of these
      kinases and proteases in a theranostic approach.

PMID- 22400064
TI  - Optical Imaging with a Cathepsin B Activated Probe for the Enhanced Detection of
      Esophageal Adenocarcinoma by Dual Channel Fluorescent Upper GI Endoscopy.
AB  - Despite significant advances in diagnosis and treatment, the prognosis of
      esophageal adenocarcinoma remains poor highlighting the importance of early
      detection. Although white light (WL) upper endoscopy can be used for screening of
      the esophagus, it has limited sensitivity for early stage disease. Thus,
      development of new imaging technology to improve the diagnostic capabilities of
      upper GI endoscopy for early detection of esophageal adenocarcinoma is an
      important unmet need. The goal of this study was to develop a method for the
      detection of malignant lesions in the esophagus using WL upper endoscopy combined
      with near infrared (NIR) imaging with a protease activatable probe (Prosense750)
      selective for cathepsin B (CTSB). An orthotopic murine model for distal
      esophageal adenocarcinoma was generated through the implantation of OE-33 and OE
      19 human esophageal adenocarcinoma lines in immunocompromised mice. The mice were
      imaged simultaneously for WL and NIR signal using a custom-built dual channel
      upper GI endoscope. The presence of tumor was confirmed by histology and target
      to background ratios (TBR) were compared for both WL and NIR imaging. NIR imaging
      with ProSense750 significantly improved upon the TBRs of esophageal tumor foci,
      with a TBR of 3.64+/-0.14 and 4.50+/-0.11 for the OE-33 and OE-19 tumors
      respectively, compared to 0.88+/-0.04 and 0.81+/-0.02 TBR for WL imaging. The
      combination of protease probes with novel imaging devices has the potential to
      improve esophageal tumor detection by fluorescently highlighting neoplastic
      regions.

PMID- 22400065
TI  - The effects of sex and gender role on responses to pressure pain.
AB  - BACKGROUND: Several studies on experimental mechanical pain suggested a strong
      influence of sex demonstrating females to be more sensitive. We examined the
      hypothesis that not only sex but also gender role affects pain responsiveness and
      looked for mediators of this effect. METHOD: As indicators of pain the threshold
      the intensity and the unpleasantness of pressure stimuli were measured, as well
      as sensory and affective quality of pain. The gender role of 74 students was
      assessed by the Bem Sex Role Inventory (BSRI). Furthermore several psychological
      variables assumed to be potential mediators (catastrophising, fear of pain,
      depressive symptoms, pain coping) were obtained. RESULTS: ANOVA revealed
      significant main effects of sex in all pain variables except affective quality of
      pain. Contrary to our hypothesis gender role had no influence on pain responses,
      neither was there an interaction of sex and gender. Fear of pain just missed the
      significance level identifying it as mediator of the sex effect on affective
      pain. CONCLUSIONS: In summary, our study corroborated previous findings that
      women are more responsive to mechanical pain stimuli with effect sizes being
      medium to large, whereas gender role did not predict any of the assessed pain
      parameters. No convincing evidence was found that the influence of sex is
      predominantly mediated by psychological characteristics of the individual.

PMID- 22400066
TI  - Inhibition of carbonic anhydrase reduces brain injury after intracerebral
      hemorrhage.
AB  - Carbonic anhydrase-1 (CA-1) is a metalloenzyme present at high concentrations in
      erythrocytes. Our previous studies showed that erythrocyte lysis contributes to
      brain edema formation after intracerebral hemorrhage (ICH) and a recent study
      indicates that CA-1 can cause blood-brain barrier disruption. The present study
      investigated the role of CA-1 in ICH-induced brain injury.There were three groups
      in the study. In the first, adult male Sprague-Dawley rats received 100 MUl
      autologous blood injection into the right caudate. Sham rats had a needle
      insertion. Rat brains were used for brain CA-1 level determination. In the second
      group, rats received an intracaudate injection of either 50 MUl CA-1 (1 MUg/MUl)
      or saline. Brain water content, microglia activation and neuronal death (Fluoro
      Jade C staining) were examined 24 hours later. In the third group, acetazolamide
      (AZA, 5 MUl, 1 mM), an inhibitor of carbonic anhydrases, or vehicle was co
      injected with 100 MUl blood. Brain water content, neuronal death and behavioral
      deficits were measured. We found that CA-I levels were elevated in the
      ipsilateral basal ganglia at 24 hours after ICH. Intracaudate injection of CA-1
      induced brain edema (79.0 +/- 0.6 vs. 78.0+/-0.2% in saline group, p<0.01),
      microglia activation and neuronal death (p<0.01) at 24 hours. AZA, an inhibitor
      of CA, reduced ICH-induced brain water content (79.3 +/- 0.7 vs. 81.0 +/- 1.0% in
      the vehicle-treated group, p<0.05), neuronal death and improved functional
      outcome (p<0.05).These results suggest that CA-1 from erythrocyte lysis
      contributes to brain injury after ICH. 

PMID- 22400063
TI  - Protease-activated drug development.
AB  - In this extensive review, we elucidate the importance of proteases and their role
      in drug development in various diseases with an emphasis on cancer. First, key
      proteases are introduced along with their function in disease progression. Next,
      we link these proteases as targets for the development of prodrugs and provide
      clinical examples of protease-activatable prodrugs. Finally, we provide
      significant design considerations needed for the development of the next
      generation protease-targeted and protease-activatable prodrugs.

PMID- 22400070
TI  - Flow cytometric analysis of immunoglobulin heavy chain expression in B-cell
      lymphoma and reactive lymphoid hyperplasia.
AB  - The diagnosis of B-cell lymphoma (BCL) is often dependent on the detection of
      clonal immunoglobulin (Ig) light chain expression. In some BCLs, the
      determination of clonality based on Ig light chain restriction may be difficult.
      The aim of our study was to assess the utility of flow cytometric analysis of
      surface Ig heavy chain (HC) expression in lymphoid tissues in distinguishing
      lymphoid hyperplasias from BCLs, and also differentiating various BCL subtypes.
      HC expression on B-cells varied among different types of hyperplasias. In
      follicular hyperplasia, IgM and IgD expression was high in mantle cells while
      germinal center cells showed poor HC expression. In other hyperplasias, B cell
      compartments were blurred but generally showed high IgD and IgM expression.
      Compared to hyperplasias, BCLs varied in IgM expression. Small lymphocytic
      lymphomas had lower IgM expression than mantle cell lymphomas. Of importance, IgD
      expression was significantly lower in BCLs than in hyperplasias, a finding that
      can be useful in differentiating lymphoma from reactive processes.

PMID- 22400069
TI  - Reactive oxygen species suppress cardiac NaV1.5 expression through Foxo1.
AB  - Na(V)1.5 is a cardiac voltage-gated Na(+) channel alphasubunit and is encoded by
      the SCN5a gene. The activity of this channel determines cardiac depolarization
      and electrical conduction. Channel defects, including mutations and decrease of
      channel protein levels, have been linked to the development of cardiac
      arrhythmias. The molecular mechanisms underlying the regulation of Na(V)1.5
      expression are largely unknown. Forkhead box O (Foxo) proteins are
      transcriptional factors that bind the consensus DNA sequences in their target
      gene promoters and regulate the expression of these genes. Comparative analysis
      revealed conserved DNA sequences, 5'-CAAAACA-3' (insulin responsive element,
      IRE), in rat, mouse and human SCN5a promoters with the latter two containing two
      overlapping Foxo protein binding IREs, 5'-CAAAACAAAACA-3'. This finding led us to
      hypothesize that Foxo1 regulates Na(V)1.5 expression by directly binding the
      SCN5a promoter and affecting its transcriptional activity. In the present study,
      we determined whether Foxo1 regulates Na(V)1.5 expression at the transcriptional
      level and also defined the role of Foxo1 in hydrogen peroxide (H(2)O(2))-mediated
      Na(V)1.5 suppression in HL-1 cardiomyocytes using chromatin immunoprecipitation
      (ChIP), constitutively nuclear Foxo1 expression, and RNAi Foxo1 knockdown as well
      as whole cell voltage-clamp recordings. ChIP with anti-Foxo1 antibody and follow
      up semi-quantitative PCR with primers flanking Foxo1 binding sites in the
      proximal SCN5a promoter region clearly demonstrated enrichment of DNA, confirming
      Foxo1 recruitment to this consensus sequence. Foxo1 mutant (T24A/S319A-GFP, Foxo1
      AA-GFP) was retained in nuclei, leading to a decrease of Na(V)1.5 expression and
      Na(+) current, while silencing of Foxo1 expression by RNAi resulted in the
      augmentation of Na(V)1.5 expression. H(2)O(2) significantly reduced Na(V)1.5
      expression by promoting Foxo1 nuclear localization and this reduction was
      prevented by RNAi silencing Foxo1 expression. These studies indicate that Foxo1
      negatively regulates Na(V)1.5 expression in cardiomyocytes and reactive oxygen
      species suppress Na(V)1.5 expression through Foxo1.

PMID- 22400071
TI  - Non-small cell lung carcinoma therapy using mTOR-siRNA.
AB  - Molecular targeting agents play important roles in non-small-cell lung cancer
      (NSCLC) therapy. Published studies have investigated new drugs categorized as
      molecular targeting agents that inhibit the mammalian target of rapamycin (mTOR).
      We focused on a small interfering RNA (siRNA) that specifically inhibits mTOR and
      has fewer side effects. To evaluate the antitumor effects of the siRNA, cell
      proliferation, apoptosis, and migration were assessed. In the study group, the
      siRNA was transfected into NSCLC cells. The number of cells present after 6 days
      of culture was counted to determine changes in cell proliferation. The level of
      apoptosis was evaluated by the detection of DNA-histone complexes in the
      cytoplasmic fraction using an absorption spectrometer. Changes in migration were
      evaluated by calculating the number of cells that passed through a specific
      filter using a commercial chemotaxis assay kit. mTOR-siRNA transfection inhibited
      cell proliferation as indicated by 37.3% (p = 0.034) decrease in the number of
      cells compared with the control cells. Analysis of the level of apoptosis in
      NSCLC cells revealed 16.7% (p = 0.016) increase following mTOR-siRNA
      transfection, and mTOR-siRNA transfection significantly inhibited cell migration
      by 39.2% (p = 0.0001). We confirmed that mTOR-siRNA induces apoptosis and
      inhibits the proliferation and migration of NSCLC cells in vitro. Further studies
      using mTOR-siRNA may aid in the development of an alternative therapy that
      maximizes the antineoplastic effect of mTOR inhibition.

PMID- 22400073
TI  - Pitfalls in immunohistochemistry--a recent example.
AB  - Immunohistochemistry is an important and valuable technique in many fields of
      research, although several common pitfalls can lead to wrong or misinterpreted
      results. A recently published study [1] claims that the protein MIA (melanoma
      inhibitory activity) is expressed in Purkinje cells in the cerebellum. Careful re
      analysis resulted in negative results. Due to these results of our group we feel
      that this analysis could serve as example for the potential problems in
      immunohistochemistry caused by the combination of an unspecific antibody and the
      omission of evaluating control tissue samples.

PMID- 22400072
TI  - Tight junctions in lung cancer and lung metastasis: a review.
AB  - Tight junctions are structures located in the apicobasal region of the cell
      membranes. They regulate paracellular solute and electrical permeability of cell
      layers. Additionally, they influence cellular polarity, form a paracellular fence
      to molecules and pathogens and divide the cell membranes to apical and lateral
      compartments. Tight junctions adhere to the corresponding ones of neighbouring
      cells and by this way also mediate attachment of the cells to one other.
      Molecules forming the membranous part of tight junctions include occludin,
      claudins, tricellulin and junctional adhesion molecules. These molecules are
      attached to scaffolding proteins such as ZO-1, ZO-2 and ZO-3 through which
      signals are mediated to the cell interior. Expression of tight junction proteins,
      such as claudins, may be up- or downregulated in cancer and they are involved in
      EMT thus influencing tumor spread. Like in tumors of other sites, lung tumors
      show changes in the expression in tight junction proteins. In this review the
      significance of tight junctions and its proteins in lung cancer is discussed with
      a focus on the proteins forming the membranous part of these structures.

PMID- 22400074
TI  - No evidence of endometriosis within serous and mucinous tumors of the ovary.
AB  - Ovarian endometriosis can transform into malignant tumors. The author
      retrospectively examined HE slides of 112 serous tumors and 75 mucinous tumors
      for the existence of ovarian endometriosis. When endometriosis is present within
      the tumors, the term "endometriosis-derived tumor" was applied. When
      endometriosis is recognized adjacent to the tumor, the term "endometriosis
      associated tumor" was used. Of the 112 serous tumors (46 benign, 18 borderline,
      and 50 malignant), 4 (3.5%) (2 benign and 2 malignant) were endometriosis
      associated tumors. None was endometriosis-derived tumor. Of the 75 mucinous
      tumors (30 benign, 26 borderline, and 19 malignant), 4 (5%) (1 borderline and 3
      benign) were endometriosis-associated tumors. No tumors showed endometriosis
      derived tumors. The data suggest that endometriosis does not transform into
      serous and mucous tumors. The author felt the limitation of retrospective survey,
      because the limited numbers of slides (5 to 15) were obtained from each tumor.
      The author also felt that endometriosis can be difficult to discern because of
      degenerative changes and other similar lesions such as fallopian tube, fimbria,
      inclusion cysts, rete ovarii, paraovarian cyst, and Mullerian ducts remnants.
      Prospective study using whole ovarian examination is required.

PMID- 22400075
TI  - Follicular thyroid adenoma dominated by spindle cells: report of two unusual
      cases and literature review.
AB  - Primary spindle cell neoplasms of the thyroid gland are quite rare. They
      encompass a heterogeneous group of benign and malignant lesions of mesenchymal
      and epithelial origin. We herein describe two unusual follicular thyroid adenomas
      dominated by spindle cells with occasional areas of colloid-forming follicular
      differentiation. The tumors affected a 77-year woman and a 70-year old man; both
      had a long-history of monoclonal gammopathy of unknown significance (MGUS). One
      tumor presented as a large cold thyroid nodule and the other was an autopsy
      finding. The tumors were predominantly composed of fibroblast-like spindled
      cells. One case showed prominent meningioma-like concentric perivascular
      arrangement and contained cytoplasmic melanin-like pigment. Stromal hyalinization
      was a prominent feature of both. By immunohistochemistry, the spindled cells
      expressed vimentin, pankeratin (KL1), thyroglobulin and TTF1 consistent with a
      follicular differentiation. They did not stain with calcitonin, CEA and other
      lineage-specific mesenchymal, neuroendocrine and melanocytic markers. There was
      no evidence of metastasis at autopsy (case 2) or at last follow-up 2 years after
      surgery (case 1). These cases demonstrate the diversity of follicular thyroid
      neoplasms and the unusual occurrence of extensive spindle cell metaplasia. These
      uncommon lesions need to be distinguished from spindle cell medullary carcinoma,
      paucicellular spindle cell anaplastic carcinoma, spindle cell foci in papillary
      and follicular carcinoma, solitary fibrous tumor and other rare benign and
      malignant mesenchymal lesions.

PMID- 22400077
TI  - Pulmonary large cell neuroendocrine carcinoma diagnosed in a brain metastasis.
AB  - The author herein reports a large cell neuroendocrine carcinoma (LCNEC) of the
      lung diagnosed at a brain metastasis without clinical data. A 70-year-old man
      underwent esophagectomy for esophageal squamous cell carcinoma, and was treated
      with chemotherapy. At 72 years of age, he was found to have prostatic well
      differentiated adenocarcinoma, and treated by estrogen. At 78 years of age, he
      was pointed out to have gastric advanced tumor, and the biopsy showed moderately
      differentiated tubular adenocarcinoma. The gastric carcinoma was treated by
      chemotherapy. At 79 years of age, he was shown to have right lung shadow (2 cm in
      diameter) and brain shadow (cerebellar vermis) of 1 cm in diameter. Multiple
      biopsy and cytology of the lung failed to detect carcinoma cells. Biopsy of the
      brain was performed. The biopsy showed medullary undifferentiated carcinoma.
      Immunohistochemically, the tumor cells were positive for pancytokeratin AE1/3,
      synaptophysin, CD56 (NCAM), p53, Ki67 (labeling 40%), KIT and TTF-1, but were
      negative for vimentin, chromogranin, neuron-specific enolase and PDGFRA. A
      pathological diagnosis of metastatic LCNEC form the lung was made. A molecular
      genetic analysis for KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18)
      genes identified no mutations of the KIT and PDGFRA genes. The patients died of
      carcinomatosis one month after the diagnosis. In conclusion, careful histological
      and immunohistochemical examination can diagnose LCNEC of the lung at the
      metastatic site.

PMID- 22400076
TI  - Prognostic value of histological features in diffuse astrocytomas WHO grade II.
AB  - The histopathological diagnosis of diffuse astrocytoma is challenging. As the WHO
      classification system is based on subjective assessments, the prognosis for the
      individual patient is somewhat uncertain. The aim of this study was therefore to
      investigate the prognostic value of various histological features, Ki-67/MIB-1
      labeling index (LI), and clinical factors. The study was designed as a
      retrospective study of 109 patients consecutively operated for their primary
      diffuse astrocytoma WHO grade II. Clinical data was collected from patient files.
      All routine stained sections were revised, and 20 different histological features
      were recorded, including cell density, atypia, mitoses, apoptoses, secondary
      structures (of Scherer), microcysts, and lymphocytic infiltration. Ki-67/MIB-1 LI
      was determined by conventional immunohistochemistry. Using uni- and multivariate
      analyses, the prognostic value of these factors was assessed as well as clinical
      parameters. Median age at primary surgery was 40 years (range 18-75). The median
      overall survival was 70 months with a minimum follow-up of 3 months. Neither
      histopathological features nor Ki-67/ MIB-1 LI (median value of 4.5% (range 0.1
      16%) indicated unfavorable prognosis. However, age > 40 years, gender (male),
      poor preoperative performance score, and biopsy rather than resection were
      significant negative prognostic factors in both uni- and multivariate analyses.
      Among diffuse grade II astrocytomas neither any histopathological trait nor Ki
      67/MIB-1 LI achieved prognostic significance, whereas clinical parameters were
      shown to serve as the major prognostic factors for these patients.

PMID- 22400078
TI  - Acute onset pyothorax-associated lymphoma (PAL) with inflammatory features.
AB  - Pyothorax-associated lymphoma (PAL) is a B-cell non-Hodgkin's lymphoma, and
      develops after 20-40 years of pyothorax or pleuritis including tuberculosis. An
      88-year-old Japanese woman developed fever and right pleural effusion. No
      mycobacterium was recognized by Ziel-Neelsen stain, culture tests and PCR
      technique in the effusion. The patient was diagnosed as non-specific pleuritis.
      No tumor formations were seen in the right pleura by imaging modalities, and she
      was treated by antibiotics. Eight months later, she complained of severe back
      pain and fever. Imaging modalities revealed many tumors in the right pleura, and
      biopsy of the tumors was performed. The biopsy showed severe diffuse
      proliferation of lymphoid cells. The lymphoid cells consisted of atypical large
      lymphoid cells and small lymphoid cells. The large atypical cells were positive
      for CD45 and CD20 but negative for CD15 and CD30, thus confirming B cell
      neoplasm. Ki-67 labeling was 79%. The small cells were positive for CD45, CD20
      and CD3, reflecting a mixture of mature B and T-cells. The small cells appeared
      non-neoplastic inflammatory cells. CD68-positive macrophages were also scattered.
      In situ hybridization for EB virus DNA showed positive signals in the large
      atypical B-cells and, to a lesser degree, in the small lymphocytes. The author
      thinks that this tumor is PAL with inflammatory reaction. The present case shows
      that the duration between PAL and pleuritis can be very short, and PAL may be
      associated with inflammatory reaction at the early neoplastic stage.

PMID- 22400079
TI  - TDT (-), KIT (+), CD34 (+), CD99 (+) precursor T lymphoblastic leukemia/lymphoma.
AB  - Although the definition of precursor T lymphoblastic lymphoma (T-LBL) is based
      only on histopathology, most cases cannot be diagnosed only by HE sections. Since
      95% of T-LBL expresses TdT and TdT is expressed only in lymphoblasts,
      immunohistochemical demonstration of TdT is mandatory for the diagnosis of TLBL.
      However, little is known about the expression of other precursor cell molecules.
      A 58-year-old woman with myelodysplastic syndrome (RAEB) became overt acute
      myelogenous leukemia (AML). She was treated twice with allogeneic peripheral
      blood stem cell transplantation from her son. Nine months later, imaging
      modalities detected a soft tissue tumor around the left ileal bone. A biopsy was
      performed. Histologically, the tumor cells were malignant polymorphic lymphoid
      cells with hyperchromatic nuclei and inconspicuous nucleoli.
      Immunohistochemically, the tumor cells are positive for CD45, CD45RO, CD34, KIT
      (CD117), CD99 (MIC-2), p53, CD10, PDGFRA, and Ki67 (labeling=60%). They were
      negative for pancytokeratin AE1/3, pancytokeratin CAM5.2, TdT, CD3, CD20,
      CD79alpha, CD43, CD56, CD57, CD30, bcl-2, kappa-chain, lambda-chain, cytokeratin
      (CK) 7, CK20, synaptophysin, chromogranin, smooth muscle actin, p63, MPO, CD68,
      lysozyme, and ASD esterase. Although TdT was negative, other precursor cell
      markers (KIT, CD34, and CD99) were positive and the lymphoid cells showed T-cell
      lineage, the diagnosis was T-LBL. The patient died of lymphoma/ leukemia 11
      months after the diagnosis. The author stress that TdT, KIT, CD34 and CD99 should
      be included in panels of precursor T-cell neoplasms. In addition, the author
      think that KIT, CD34 and CD99 are helpful for the diagnosis of T-LBL in cases
      negative for TdT. Further, it is unique that this case was not myeloid sarcoma
      but precursor T-cell neoplasm, and that T-LBL develops during AML.

PMID- 22400080
TI  - Primary signet-ring cell carcinoma of the lung: a case report with an
      immunohistochemical study.
AB  - Primary signet-ring cell adenocarcinoma (SRCA) of the lung is very rare. A 78
      year-old man consulted to our hospital because of loss of appetite. Physical
      examination showed lymphadenopathy of the cervical lymph nodes. Chest X-ray
      showed a tumor of the right upper lobe. Blood laboratory test showed an increase
      of LDH and CRP. Tumor markers (CYFRA, SCC, CEA, ProGRP) were within normal range.
      Clinical diagnosis was suspected malignant lymphoma of the lung. Transbronchial
      lung biopsies showed SRCA (70%) mixed with poorly differentiated adenocarcinoma
      (30%). The SRCA cells were positive for mucins. Immunohistochemically, the SRCA
      cells were positive for cytokeratin (CK) AE1/3, CK CAM5.2, CK7, CK18, EMA, p53,
      Ki-67 (labeling=60%), CEA, CA19-9, TTF-1, and MUC1. They were negative for
      CK34BE12, CK5/6, CK8, CK14, CK19, CK20, vimentin, chromogranin, synaptophysin,
      CD45, CD20, CD3, surfactant Apoprotein-A, CDX-2, MUC2, MUC5AC and MUC6. A
      pathological diagnosis of SRCA of the lung was made. The patient showed downhill
      course, and died of carcinomatosis 3 months after the first manifestation. In
      conclusion, a vary rare case of primary pulmonary SRCA was reported with an
      immunohistochemical study.

PMID- 22400081
TI  - Cutaneous metastasis of renal cell carcinoma: a report of two cases.
AB  - Cutaneous metastasis of renal cell carcinoma (RCC) is very rare. The author
      herein report two cases of RCC with cutaneous metastasis. Case 1: is a 75-year
      old man with right lumbago. Imaging modalities including CT and MRI revealed a
      right renal tumor. Nephrectomy was performed. Pathological diagnosis of the renal
      tumor was RCC of clear cell type (Fuhrman's grade II). He denied follow-up. Nine
      years later, he (at the age of 84 years), a neck skin tumor emerged. Clinical
      diagnosis was hemangioma. Imaging modalities including CT and MRI showed several
      tumors in both lungs. The resection of the neck tumor was performed. The tumor
      was composed of clear cell type arranged in a trabecular pattern.
      Immunohistochemically, the tumor cells were positive for pancytokeratins,
      cytokeratin 18, CD10, Ki-67 (labeling=13%), but negative for CD34, factor-VIII
      related antigen, CEA, EMA, melanosome (HMB45), S100 protein, p53, and HepPar-1.
      Metastatic RCC was diagnosed. Despite interferon therapy, he died of 6 months
      after the second admission. Case 2 is a 66-year-old man with gross hematuria.
      Imaging modalities revealed left renal tumor. A nephrectomy was performed. The
      pathological diagnosis was RCC of clear cell type (grade II). The tumor was
      invasive into the renal pelvis. He was treated by chemoradiation, but metastases
      of lungs, skin (thigh), and lib emerged, and died of cachexia 9 months after the
      admission. Necropsy of the skin tumor was performed. The skin tumor was composed
      of clear cells arranged in a trabecular pattern. Immunohistochemically, the tumor
      cells were positive for pancytokeratins (AE1/3, CAM5.2), CD10, p53, and Ki-67
      (labeling=20%), but negative for CD34, factor-VIII-related antigen, CEA,
      melanosome (HMB45), S100 protein, and HepPar-1. A diagnosis of RCC (grade II) was
      diagnosed.

PMID- 22400082
TI  - Primary diffuse large B-cell lymphoma of the submandibular gland.

PMID- 22400084
TI  - Transjugular intrahepatic porto-systemic shunt in the elderly: Palliation for
      complications of portal hypertension.
AB  - AIM: To present a dedicated series of transjugular intrahepatic porto-systemic
      shunts (TIPS) in the elderly since data is sparse on this population group.
      METHODS: A retrospective review was performed of patients at least 65 years of
      age who underwent TIPS at our institutions between 1997 and 2010. Twenty-five
      patients were referred for TIPS. We deemed that 2 patients were not considered
      appropriate candidates due to their markedly advanced liver disease. Of the 23
      patients suitable for TIPS, the indications for TIPS placement was portal
      hypertension complicated by refractory ascites alone (n = 9), hepatic hydrothorax
      alone (n = 2), refractory ascites and hydrothorax (n = 1), gastrointestinal
      bleeding alone (n = 8), gastrointestinal bleeding and ascites (n = 3). RESULTS:
      Of these 23 attempted TIPS procedure patients, 21 patients had technically
      successful TIPS procedures. A total of 29 out of 32 TIPS procedures including
      revisions were successful in 21 patients with a mean age of 72.1 years (range 65
      82 years). Three of the procedures were unsuccessful attempts at TIPS and 8
      procedures were successful revisions of our existing TIPS. Sixteen of 21 patients
      who underwent successful TIPS (excluding 5 patients lost to follow-up) were
      followed for a mean of 14.7 mo. Ascites and/or hydrothorax was controlled
      following technically successful procedures in 12 of 13 patients. Bleeding was
      controlled following technically successful procedures in 10 out of 11 patients.
      CONCLUSION: We have demonstrated that TIPS is an effective procedure to control
      refractory complications of portal hypertension in elderly patients.

PMID- 22400085
TI  - Evaluation of adherence to oral antiviral hepatitis B treatment using structured
      questionnaires.
AB  - AIM: To assess adherence rates to nucleos(t)ide analogues (NUCs) therapy in
      patients with chronic hepatitis B virus infection and determine factors
      associated with adherence. METHODS: The questionnaire study was conducted in the
      liver clinics at Concord Repatriation General Hospital. All patients who were
      currently taking one or more NUCs were asked to complete a structured, self
      administered 32-item questionnaire. Adherence was measured using visual analogue
      scales. The patient's treating clinician was also asked to assess their patient's
      adherence via a structured questionnaire. RESULTS: A total of 80 patients
      completed the questionnaire. Sixty six percent of the patients (n = 49) reported
      optimal adherence whilst 25 (33.8%) graded their adherence to NUCs as suboptimal.
      Thirty four (43%) patients reported to have omitted taking their NUCs sometime in
      the past. Recent non-adherence was uncommon. Amongst the patients who reported
      skipping medications, the most common reason cited was "forgetfulness" (n = 27,
      56.25%). Other common reasons included: ran out of medications (n = 5, 10.42%),
      being too busy (n = 4, 8.33%) and due to a change in daily routine (n = 5,
      10.42%). Patients who reported low adherence to other prescription pills were
      also more likely to miss taking NUCs (P = 0.04). Patients who were under the care
      of a language-discordant clinician were also more likely to report suboptimal
      adherence to NUCs (P = 0.04). CONCLUSION: Adherence rates were much less than
      that expected by the physician and has potential adverse affect on long term
      outcome. Communication and education appear central and strategies need to be
      implemented to improve ongoing adherence.

PMID- 22400083
TI  - Concept of the pathogenesis and treatment of cholelithiasis.
AB  - Gallstone disease (GD) is a chronic recurrent hepatobiliary disease, the basis
      for which is the impaired metabolism of cholesterol, bilirubin and bile acids,
      which is characterized by the formation of gallstones in the hepatic bile duct,
      common bile duct, or gallbladder. GD is one of the most prevalent
      gastrointestinal diseases with a substantial burden to health care systems. GD
      can result in serious outcomes, such as acute gallstone pancreatitis and
      gallbladder cancer. The epidemiology, pathogenesis and treatment of GD are
      discussed in this review. The prevalence of GD varies widely by region. The
      prevalence of gallstone disease has increased in recent years. This is connected
      with a change in lifestyle: reduction of motor activity, reduction of the
      physical load and changes to diets. One of the important benefits of early
      screening for gallstone disease is that ultrasonography can detect asymptomatic
      cases, which results in early treatment and the prevention of serious outcomes.
      The pathogenesis of GD is suggested to be multifactorial and probably develops
      from complex interactions between many genetic and environmental factors. It
      suggests that corticosteroids and oral contraceptives, which contain hormones
      related to steroid hormones, may be regarded as a model system of cholelithiasis
      development in man. The achievement in the study of the physiology of bile
      formation and the pathogenesis of GD has allowed expanding indications for
      therapeutic treatment of GD.

PMID- 22400086
TI  - Managing change in healthcare.

PMID- 22400087
TI  - Childhood multiple sclerosis and related disorders.
AB  - Multiple sclerosis (MS) in children and adolescents is increasingly recognized
      worldwide. Demyelinating disorders of the central nervous system may overlap
      considerably in their clinical presentation and radiological appearance.
      Therefore an exact categorization might be challenging and might not be readily
      attainable. Rigorous radiological and laboratory investigations and longitudinal
      follow up of the patient are needed in order to establish the diagnosis of a
      chronic demyelinating disorder especially in children. However, in the past few
      years many advances have been achieved in the field of pediatric MS and other
      white matter disease such as establishing diagnostic criteria, consensus
      definitions proposed for pediatric multiple sclerosis and related disorders and
      advances in treating such disorders. A wealth of knowledge regarding childhood MS
      have been established with vast speed and greater familiarity with the diagnosis
      and treatment options should lead to better care of children with such disorders.
      This review will present the important advances in childhood multiple sclerosis
      and related disorders that were achieved in the last few years.

PMID- 22400088
TI  - Type 2 Diabetes and its Characteristics during Ramadan in Dhahira Region, Oman.
AB  - OBJECTIVE: The main objective of this study is to illustrate the various
      characteristics including care of patients and changes in lifestyle of type 2
      diabetics during Ramadan in Dhahira region, Oman. METHODS: This was a hospital
      based study conducted during the month of Ramadan in 2006. Of the 453 recruited,
      334 (73.7%) with complete data were analyzed. Student t test was used for
      comparison of means and Chi-square test for proportions. RESULTS: We analyzed 334
      patients with type 2 diabetes. The common complication associated with diabetes
      was coronary artery disease (19.5%) and nearly 60% of the study subjects had
      hypertension as co-morbidity. There was little or no change in the lifestyle
      activities and Insulin/Oral AntiDiabetic Drug (OAD) doses during Ramadan.
      Majority of diabetics had poorly controlled Fasting Blood Sugar (FBS) and Body
      Mass Index (BMI). The overall mean weight change was -0.49 +/- 1.54 SD. There was
      a significant weight loss during Ramadan (p<0.05). CONCLUSION: The large
      proportions of uncontrolled type 2 diabetes patients in our region represent a
      challenge to our physicians during Ramadan. There is a need to improve diabetic
      management and intensive education before fasting. Clear guidelines for diabetic
      management including uncontrolled diabetics during Ramadan are essential in Oman.

PMID- 22400089
TI  - A retrospective study of ureteroscopy performed at the sultan qaboos hospital,
      salalah from august 2001 -august 2006.
AB  - In the modern era of management of disorders of the upper urinary tract,
      ureteroscopy forms an important part in the armamentarium for the diagnosis and
      treatment of a variety of disorders that occur in the upper urinary tracts. The
      modern ureteroscopes have better vision and are less traumatic, making
      ureteroscopy a relatively safe procedure. Major complications are rare. An audit
      of a total of 128 ureteroscopies done in the Department of Urology over a six
      year period from August 2001 till August 2006 at the Sultan Qaboos Hospital,
      Salalah, was undertaken. The results are discussed in detail and compared with
      results from other centers. The management of a rare but dreaded major
      complication is discussed in detail.

PMID- 22400090
TI  - Continuing Medical Education Strategy for Primary Health Care Physicians in Oman:
      Lessons to be learnt.
AB  - INTRODUCTION: Continuing medical education (CME) is important for professional
      development, to improve doctors' clinical performance that ultimately influences
      the quality of the health outcomes. In the presence of an increasing number of
      family physicians serve in the primary health care system upon graduation in Oman
      make us to consider the meta-cognition of the leaner and engaged them in learning
      process. The purpose of this paper is to examine ways of improving the continuing
      education methods for the physicians. OBJECTIVE: To assess the preferred method
      of continuing education for primary health care physicians. METHODS: We conducted
      a program evaluation among a group of general physicians who were involved in
      some of the activities in continuing education at end of their program in the
      Muscat region health centres in Oman. The main outcome measure was to study the
      preferred method for CME. RESULTS: The majority of the participants believe that
      continuing medical education improves their practice. In addition, the finding
      suggests that small group learning and combination of methods are the preferred
      methods of continuing education for primary health care physicians. CONCLUSION:
      Interactive small group learning is shown to be more effective to achieve the
      learning objectives and ultimately improve practice. Practice-based small group
      learning is the method we recommended.

PMID- 22400091
TI  - Evaluation of diagnostic fasting in the investigation of hypoglycemia in children
      omani experienc.
AB  - OBJECTIVES: To assess the safety and importance of diagnostic fast in the
      evaluation of hypoglycemia in children in a non-specialist set up. METHOD: The
      medical records of 116 patients with hypoglycemia, admitted to Pediatric Unit,
      Royal Hospital, Muscat, Sultanate of Oman, over a 15 year period, were reviewed.
      Of these, 96 (82.8%) patients, 52 boys and 44 girls, aged 8 days to 10 years were
      subjected to diagnostic fast. RESULTS: Of these 96 patients fasted, 77 (80.2%)
      became hypoglycemic (HG group) and 19 (19.8 %) did not develop hypoglycemia on
      fast (NHG group). In the HG group, 69 (89.6%) patients developed symptomatic
      hypoglycemia of variable severity and none developed coma or convulsions during
      fasting. CONCLUSION: The study has proved that diagnostic fast is relatively a
      safe procedure with considerable amount of diagnostic yield.

PMID- 22400092
TI  - Tear film status in patients attending the eye clinic in South sharqiya region.
AB  - OBJECTIVE: To study the tear film profile of patients attending the eye clinic of
      Sur hospital of South Sharqiya region of Oman and to study the epidemiology of
      patients having abnormal tear film profile. METHOD: Patients attending the eye
      clinic of Sur hospital and B. Ali eye clinic were asked about the clinical
      symptoms relevant to dry eye and subjected to tear film tests namely TBUT (Tear
      Break up Time) and Schirmer's 1 to assess tear film profile. Patients with
      irregular corneas were excluded from the study. Overall 127 patients were
      included in the study. RESULTS: 42.5% (95% CI: 33.9% to 51.1%) of patients
      examined had abnormal tear film profile with patients >30 years 56.75% (95% CI:
      45.4% to 68%) showing abnormality more often and females 40.3% (95% CI: 29.3% to
      51.2%) outnumbered males. Burning was the main symptom in patients with abnormal
      tear film profile. CONCLUSION: We infer that a large number of patients had
      abnormal tear film profile most of them were asymptomatic and trachoma figured
      prominently amongst the diseases in cases with abnormal tear film profile.

PMID- 22400093
TI  - Scarf osteotomy - Is it the procedure of choice in hallux valgus surgery? A
      preliminary report.
AB  - Many procedures are described in the literature for the surgical management of
      hallux valgus. There are over 130 surgical procedures described but the surgeon
      usually limits these to a few which he is comfortable with and which gives the
      best aesthetic and functional result to the patient. There is ever rising
      enthusiasm among orthopaedic surgeons regarding diaphyseal osteotomy ever since
      Burutaran described the procedure in 1973. Weil in United States and Barouk in
      Europe popularized the technique. Scarf is a double chevron diaphyseal osteotomy
      which is inherently more stable than other osteotomies on the first metatarsal
      and allows early return to work. The author reports his early experience with
      SCARF osteotomy, which is a comparatively new technique for hallux valgus
      correction which was done in Ibri Regional Hospital in the Sultanate of Oman. All
      patients who presented with symptomatic hallux valgus were taken up and there
      were three patients who required surgical intervention for hallux valgus. The
      purpose of this study was to find its effectiveness in terms of stability of the
      osteotomy and early return to work. Proximal phalangeal osteotomy was not found
      necessary in none of the three cases operated by us. Scarf osteotomy is safe and
      found to give better aesthetic and functional result and early return to work.
      All our three patients had good functional recovery and early return to work.

PMID- 22400094
TI  - Primary Health Care Consumers' Acceptance, Trust and Gender Preferences towards
      Omani Doctors.
AB  - BACKGROUND: The percentage of Omani physicians from total number of physicians
      working in the Sultanate tripled from 9% in 1999 to 27% in 2006 and is expected
      to increase to 50% by 2010. The study aimed to asses community attitudes towards
      Omani doctors and to investigate the different socio-demographic variables
      related to these attitudes. METHOD: It was done in two selected Primary Health
      Care (PHC) facilities by simple random technique in Batinah region. Face-to-face
      interview was made on 305 randomly selected samples of PHC customers by trained
      researchers from Sultan Qaboos University (SQU). Omani Doctors Acceptance Scale
      (ODAS) was adapted and used to assess participants acceptance of the
      communication skills of the Omani doctor, care to the patient, absence of
      language barrier, competence level, preference to be seen by doctor from the same
      sex, embarrassment from seeing an Omani doctor, qualification, experience,
      knowledge and skills of the Omani experience of the Omani doctor, and trust on
      the Omani doctor. Chi squared tests of significance was used in analysis.
      RESULTS: Males reported more satisfaction about communication skills of the Omani
      doctors, whereas female respondents reported higher likelihood of being
      embarrassed from the latter. Elder age cohort, those reported ever treated by an
      Omani doctor, married respondents, and those of lower level of education were
      more likely to report higher level of acceptance than others. Those aged 26-40
      and those above 40 years of age were 2.41 and 3.41 times higher than the youngest
      age cohort respectively. Similarly, older age cohort reported having more trust
      than the middle age respondents relatively to the youngest age group. CONCLUSION:
      The current study showed an accepted level of acceptance to Omani doctors.
      Looking for crucial issues in patient-doctor relationships as acceptance,
      satisfaction, trust, gender preference especially for PHC doctors ensure the
      continuity of care.

PMID- 22400095
TI  - Acute lead poisoning in an infant.
AB  - A case of acute lead poisoning in an infant without overt clinical manifestations
      of encephalopathy is reported for the first time in Oman. The case was diagnosed
      at Rustaq Hospital on the basis of (i) history by the mother of giving the child
      a traditional remedy for treating constipation (ii) X-ray of abdomen showing
      radio-opaque speckles and (iii) detection of high blood lead levels (83.3 ug/dL)
      at the toxicology laboratory of the poison control centre. The source of lead was
      confirmed by high content of inorganic lead (20.2%) found in the sample of the
      traditional remedy (bint al dahab). The blood lead levels significantly
      decreased, after the intravenous calcium edetate (EDTA) therapy was given to the
      baby. The case highlights that early detection and treatment of acute lead
      poisoning in children can prevent morbidity and sequelae associated with
      encephalopathy. It also indicated the need for awareness and prevention programme
      for parents on this issue.

PMID- 22400096
TI  - Uncommon presentation of congenital lacrimal duct obstruction a case report of
      congenital amniontocele.
AB  - BACKGROUND: Congenital amniontocele also known as congenital dacryocystocele is
      an uncommon variant of a very common condition (Naso-Lacrimal Duct Obstruction,
      NLDO) that affects newborn babies. The congenital amniontocele causes obstruction
      of the lacrimal drainage system creating a cystic swelling of the lacrimal sac.
      It usually presents at birth or soon after birth, as a bluish swelling, below and
      nasal to the medial canthus. If the congenital amniontocele is associated with
      intranasal cystic swelling of the NLD and if it is large and bilateral it can
      cause severe respiratory distress particularly during milk feeding. METHOD: We
      report a case of 24 days old female newborn baby who were presented to us from
      pediatric clinic of Rustaq Hospital with bluish cystic swelling below the left
      medial canthus soon after the birth. CONCLUSION: Congenital amniontocele is
      relatively rare and the literature describes a variable natural course of these
      lesions with resultant controversy in their management. Usually congenital
      amniontocele resolves spontaneously with conservative management, and if not,
      dacryocystitis might develop. Treatment of congenital amniontocele comprises
      digital sac massaging and early probing the lacrimal system,(8) or some times,
      intranasal surgery in the form of marsupialization of the intranasal cyst, this
      is usually performed endoscopically.(7) We report successful conservative
      management in our case and recommend this with oral and topical antibiotics with
      lacrimal sac massage for 7 to 10 days and, if there is no response, to consider
      surgical intervention in the form of lacrimal probing.

PMID- 22400097
TI  - Coomb's Positive Hemolytic Anemia Due To Insect Bite.
AB  - Hemolytic anemia has occasionally been described in association with insect
      bites. The venom of certain spiders, bees and wasps, and some snakes can rarely
      cause intravascular hemolysis. We report here a case of Coombs positive hemolytic
      anemia due to an insect bite. These bites often pose diagnostic challenges and
      when associated with systemic manifestations necessitate early intervention. This
      communication reviews the clinico- hematologic spectrum in these cases and also
      emphasizes the need to capture the insect as identification would help in early
      diagnosis and management.

PMID- 22400098
TI  - Clinical profile of five patients with Rett syndrome and literature review.
AB  - Five girls aged 4 to 13 years presented with clinical features of classical Rett
      syndrome - loss of acquired developmental skills including speech and hand
      function, progressive microcephaly and characteristic stereotyped "hand washing"
      movements. Two patients had generalized tonic, clonic seizures and one had atonic
      seizures with electroencephalogram (EEG) evidence of Lannox Gastaut syndrome.
      Cranial CT was normal in all except two patients, which showed marked perisylvian
      atrophy, and metabolic screening revealed non specific mild hyperammoniaemia in
      three. The aim of the study is to illustrate the unique clinical features of Rett
      syndrome and reiterate the importance of the diagnosis of this rare condition,
      clinically.

PMID- 22400099
TI  - Snow storm pattern.

PMID- 22400100
TI  - Hemoglobin H disease in Muscat, Oman - A 5 year study.
AB  - OBJECTIVES: Published data indicate that Alpha thalassemia trait is prevalent in
      45% of population of Sultanate of Oman. Recent unpublished data suggest that this
      prevalence is higher than 45%. Yet clinical suspicion or investigations into
      alpha-thalassemias are lacking. Moreover, Hemoglobin H disease is considered rare
      in Oman. We decided, therefore to look for Hemoglobin H disease and characterize
      the clinico-hematopathological features of the disease. METHODS: Patient
      demographics, clinical details and detailed hematology parametry of Hemoglobin H
      disease cases, diagnosed by Department of Laboratory over a period of 5 years
      between February 2002 and January 2007 in patients presenting at Al-Nahdha
      Hospital and Genetic counseling unit in Muscat were compiled from hospital and
      laboratory records and analyzed. RESULTS: Twenty cases of Hemoglobin H disease in
      Omanis were diagnosed mainly during the second decade. 60% belonged to Al-Balushi
      tribe. 40% of cases presented with body pains. 35% presented with nonspecific
      symptoms. 50% of cases were erroneously labeled as Iron deficiency anemia.
      Microcytic erythrocytosis, high Red Cell Distribution Width, numerous misshapen
      Red Blood Cells, pseudothrombocytosis, low A2 and normal Ferritin were important
      diagnostic clues. Hemoglobin H inclusions in special reticulocyte smears and
      Hemoglobin H on HPLC or Electrophoresis were diagnostic. CONCLUSION: Hemoglobin H
      disease is common in Oman. The need to do HPLC, G6PD activity and Ferritin
      studies in all cases of anemia in Oman to avoid missing diagnosis of Hemoglobin H
      disease is stressed. This study is intended to create awareness about Hemoglobin
      H disease in order to diagnose early, treat rightly, counsel correctly and pave
      the path for prevention of alpha-thalassemia disease in Oman.

PMID- 22400101
TI  - Photo-induced proton gradients for the in vitro investigation of bacterial efflux
      pumps.
AB  - We describe an original activity assay for membrane transport that uses the
      proton motive force-dependent efflux pump MexAB from Pseudomonas aeruginosa. This
      pump is co-reconstituted into proteoliposomes together with bacteriorhodopsin
      (BR), a light-activated proton pump. In this system, upon illumination with
      visible light, the photo-induced proton gradient created by the BR is shown to be
      coupled to the active transport of substrates through the pump.

PMID- 22400102
TI  - Effect of Selenium on HLA-DR Expression of Thyrocytes.
AB  - Autoimmune thyroid diseases (ATDs) represent the most frequent forms of the organ
      specific autoimmune thyroid disorders that result from interaction between
      genetic and environmental factors. Selenium has been shown to exert a beneficial
      effect on the autoimmune thyroiditis. In spite of therapeutical effect of
      selenium on autoimmunity, the mechanism of its action has not been revealed.
      Objective. To determine whether selenium in vitro thyrocytes cultures are able to
      influence the HLA-DR molecule expression of human thyrocytes and production of
      free oxygen radicals. Method. Thyrocytes were prepared from human thyroid gland
      and cultured in vitro in the presence of interferon-gamma and sodium selenite.
      The expression of HLA-DR molecules induced by interferon-gamma in the presence of
      sodium selenite of various concentration was measured by fluorescence-activated
      cell sorter. Results. Selenium has a dose-dependent inhibitory effect on the
      expression of HLA-DR molecules of thyrocytes induced by interferon-gamma. This
      effect of selenium was in the inverse correlation with antioxidative capacity.
      Conclusion. Beneficial effect of selenium on autoimmune mechanism is a complex
      mechanism in which the inhibitory effect on HLA-DR molecule expression and
      antioxidative capacity are involved into therapy of autoimmune thyroiditis.

PMID- 22400103
TI  - Spondyloarthropathies in autoimmune diseases and vice versa.
AB  - Polyautoimmunity is one of the major clinical characteristics of autoimmune
      diseases (ADs). The aim of this study was to investigate the prevalence of ADs in
      spondyloarthropathies (SpAs) and vice versa. This was a two-phase cross-sectional
      study. First, we examined the presence of ADs in a cohort of patients with SpAs
      (N = 148). Second, we searched for the presence of SpAs in a well-defined group
      of patients with ADs (N = 1077) including rheumatoid arthritis (RA), systemic
      lupus erythematosus (SLE), and Sjogren's syndrome (SS). Among patients with SpAs,
      ankylosing spondylitis was observed in the majority of them (55.6%). There were
      two patients presenting with SS in the SpA group (1.4%) and 5 patients with
      autoimmune thyroiditis (3.5%). The global prevalence of ADs in SpAs was 4.86%. In
      the ADs group, there were 5 patients with SpAs (0.46%). Our results suggest a
      lack of association between SpAs and ADs. Accordingly, SpAs might correspond more
      to autoinflammatory diseases rather than to ADs.

PMID- 22400104
TI  - Successes and Challenges in an Integrated Tuberculosis/HIV Clinic in a Rural,
      Resource-Limited Setting: Experiences from Kericho, Kenya.
AB  - Objective. To describe TB/HIV clinic outcomes in a rural, Ministry of Health
      hospital. Design. Retrospective, secondary analyses. Descriptive statistics and
      logistic regression analyses evaluated baseline characteristics and outcomes.
      Results. Of 1,911 patients, 89.8% were adults aged 32.0 (+/-12.6) years with
      baseline CD4 = 243.3 (+/-271.0), 18.2% < 50 cells/mm(3). Pulmonary (84.8%, (32.2%
      smear positive)) exceeded extrapulmonary TB (15.2%). Over 5 years, treatment
      success rose from 40.0% to 74.6%, lost to follow-up dropped from 36.0% to 12.5%,
      and deaths fell from 20.0% to 5.4%. For patients starting ART after TB treatment,
      those with CD4 >= 50 cells/mm(3) were twice as likely to achieve treatment
      success (OR = 2.0, 95% CI = 1.3-3.1) compared to those with CD4 < 50 cells/mm(3).
      Patients initiating ART at/after 2 months were twice as likely to achieve
      treatment success (OR = 2.0, 95% CI = 1.3-3.3). Yearly, odds of treatment success
      improved by 20% (OR = 1.2, 95% CI = 1.0-1.5). Conclusions. An integrated TB/HIV
      clinic with acceptable outcomes is a feasible goal in resource-limited settings.

PMID- 22400105
TI  - Older Adults Accessing HIV Care and Treatment and Adherence in the IeDEA Central
      Africa Cohort.
AB  - Background. Very little is known about older adults accessing HIV care in sub
      Saharan Africa. Materials and Methods. Data were obtained from 18,839 HIV
      positive adults at 10 treatment programs in Burundi, Cameroon, and the Democratic
      Republic of Congo. We compared characteristics of those aged 50+ with those aged
      18-49 using chi-square tests. Logistic regression was used to determine if age
      was associated with medication adherence. Results. 15% of adults were 50+ years.
      Those aged 50+ were more evenly distributed between women and men (56% versus
      44%) as compared to those aged 18-49 (71% versus 29%) and were more likely to be
      hypertensive (8% versus 3%) (P < 0.05). Those aged 50+ were more likely to be
      adherent to their medications than those aged 18-49 (P < 0.001). Adults who were
      not heavy drinkers reported better adherence as compared to those who reported
      drinking three or more alcoholic beverages per day (P < 0.001). Conclusions.
      Older adults differed from their younger counterparts in terms of medication
      adherence, sociodemographic, behavioral, and clinical characteristics.

PMID- 22400107
TI  - A Comparison of Patient Satisfaction with Emergency Department Opt-In and Opt-Out
      Rapid HIV Screening.
AB  - Study objective. To compare patient satisfaction with emergency department (ED)
      opt-in and opt-out HIV screening. Methods. We conducted a survey in an urban ED
      that provided rapid HIV screening using opt-in (February 1, 2007-July 31, 2007)
      and opt-out (August 1, 2007-January 31, 2008) approaches. We surveyed a
      convenience sample of patients that completed screening in each phase. The
      primary outcome was patient satisfaction with HIV screening. Results. There were
      207 and 188 completed surveys during the opt-in and opt-out phases, respectively.
      The majority of patients were satisfied with both opt-in screening (95%, 95%
      confidence interval [CI] = 92-98) and opt-out screening (94%, 95% CI = 89-97).
      Satisfaction ratings were similar between opt-in and opt-out phases even after
      adjusting for age, gender, race/ethnicity, and test result (adjusted odds ratio
      1.3, 95% CI = 0.5-3.1). Conclusions. Emergency department patient satisfaction
      with opt-in and opt-out HIV screening is similarly high.

PMID- 22400106
TI  - Barriers to Initiation of Pediatric HIV Treatment in Uganda: A Mixed-Method
      Study.
AB  - Although the advantages of early infant HIV diagnosis and treatment initiation
      are well established, children often present late to HIV programs in resource
      limited settings. We aimed to assess factors related to the timing of treatment
      initiation among HIV-infected children attending three clinical sites in Uganda.
      Clinical and demographic determinants associated with early disease (WHO clinical
      stages 1-2) or late disease (stages 3-4) stage at presentation were assessed
      using multilevel logistic regression. Additionally, semistructured interviews
      with caregivers and health workers were conducted to qualitatively explore
      determinants of late disease stage at presentation. Of 306 children initiating
      first-line regimens, 72% presented late. Risk factors for late presentation were
      age below 2 years old (OR 2.83, P = 0.014), living without parents (OR 3.93, P =
      0.002), unemployment of the caregiver (OR 4.26, P = 0.001), lack of perinatal HIV
      prophylaxis (OR 5.66, P = 0.028), and high transportation costs to the clinic (OR
      2.51, P = 0.072). Forty-nine interviews were conducted, confirming the identified
      risk factors and additionally pointing to inconsistent referral from perinatal
      care, caregivers' unawareness of HIV symptoms, fear, and stigma as important
      barriers. The problem of late disease at presentation requires a multifactorial
      approach, addressing both health system and individual-level factors.

PMID- 22400108
TI  - Risk Factors for Anemia among Brazilian Infants from the 2006 National
      Demographic Health Survey.
AB  - Iron deficiency is an important public health problem. An understanding of anemia
      risk factors is essential to informed health policies. We performed a cross
      sectional study of 1,382 infants from the 2006 Brazilian National Survey on
      Demography and the Health of Women and Children. Mild and moderate anemia was
      characterised by hemoglobin levels below 11.0 and 9.5 g/dL, respectively. Rates
      for mild and moderate anemia were 25.9% and 9.9%, respectively. The logistic
      model included three risk factors for mild anemia-urban residence area (OR = 2.5;
      P = 0.004), fever in the past 2 weeks (OR = 2.4; P < 0.001), and age less than 12
      months (OR = 1.7; P = 0.024). Strategies to control infant anemia should include
      health promotion and nutritional education for families from all socioeconomic
      levels. Lifestyle quality improvement based on adequate food consumption must be
      achieved by communities in all macroregions, and especially in urban areas.

PMID- 22400109
TI  - Can transthoracic echocardiography be used to predict fluid responsiveness in the
      critically ill patient? A systematic review.
AB  - Introduction. We systematically evaluated the use of transthoracic
      echocardiography in the assessment of dynamic markers of preload to predict fluid
      responsiveness in the critically ill adult patient. Methods. Studies in the
      critically ill using transthoracic echocardiography (TTE) to predict a response
      in stroke volume or cardiac output to a fluid load were selected. Selection was
      limited to English language and adult patients. Studies on patients with an open
      thorax or abdomen were excluded. Results. The predictive power of diagnostic
      accuracy of inferior vena cava diameter and transaortic Doppler signal changes
      with the respiratory cycle or passive leg raising in mechanically ventilated
      patients was strong throughout the articles reviewed. Limitations of the
      technique relate to patient tolerance of the procedure, adequacy of acoustic
      windows, and operator skill. Conclusions. Transthoracic echocardiographic
      techniques accurately predict fluid responsiveness in critically ill patients.
      Discriminative power is not affected by the technique selected.

PMID- 22400110
TI  - Sepsis and AKI in ICU Patients: The Role of Plasma Biomarkers.
AB  - Given the higher mortality rate of ICU patients with sepsis and AKI, we decided
      to investigate the possible correlation between serum biomarkers of organ damage,
      and endotoxin activity in ICU septic patients. Ninety-eight consecutive adult
      patients were enrolled in this study. Patients were divided in two groups
      depending on the presence of sepsis. Fifty-six patients had sepsis, while forty
      two patients were nonseptic. Among septic patients, twenty-four subjects
      developed AKI, while thirty-two did not. AKI occurred in fourteen patients
      without sepsis as well. The levels of NGAL, BNP, and AOPP were significantly
      higher among septic patients compared with nonseptic subjects (P < 0.001). Among
      septic patients, subjects who developed AKI showed significant higher levels of
      NGAL and AOPP (P = 0.0425) and BNP (P = 0.0327). Among patients who developed
      AKI, a significant difference was found only in terms of AOPP levels between
      septic and nonseptic patients. The correlation between endotoxin activity and BNP
      in septic patients and the increase in the levels of NGAL, BNP, and AOPP in case
      of sepsis and AKI, in particular if they are associated, indicate a multiorgan
      involvement in these two conditions.

PMID- 22400111
TI  - beta-Catenin Signalling in Glioblastoma Multiforme and Glioma-Initiating Cells.
AB  - Glioblastoma multiforme (GBM) is a commonly occurring brain tumor with a poor
      prognosis. GBM can develop both "de novo" or evolve from a previous astrocytoma
      and is characterized by high proliferation and infiltration into the surrounding
      tissue. Following treatment (surgery, radiotherapy, and chemotherapy), tumors
      often reappear. Glioma-initiating cells (GICs) have been identified in GBM and
      are thought to be responsible for tumors initiation, their continued growth, and
      recurrence. beta-catenin, a component of the cell-cell adhesion complex and of
      the canonical Wnt pathway, regulates proliferation, adhesion, and migration in
      different cell types. beta-catenin and components of the Wnt canonical pathway
      are commonly overexpressed in GBM. Here, we review previous work on the role of
      Wnt/beta-catenin signalling in glioma initiation, proliferation, and invasion.
      Understanding the molecular mechanisms regulating GIC biology and glioma
      progression may help in identifying novel therapeutic targets for GBM treatment.

PMID- 22400112
TI  - Methodology for Anti-Gene Anti-IGF-I Therapy of Malignant Tumours.
AB  - The aim of this study was to establish the criteria for methodology of cellular
      "anti-IGF-I" therapy of malignant tumours and particularly for glioblastoma
      multiforme. The treatment of primary glioblastoma patients using surgery,
      radiotherapy, and chemotherapy was followed by subcutaneous injection of
      autologous cancer cells transfected by IGF-I antisense/triple helix expression
      vectors. The prepared cell "vaccines" should it be in the case of glioblastomas
      or other tumours, have shown a change of phenotype, the absence of IGF-I protein,
      and expression of MHC-I and B7. The peripheral blood lymphocytes, PBL cells,
      removed after each of two successive vaccinations, have demonstrated for all the
      types of tumour tested an increasing level of CD8(+) and CD8(+)28(+) molecules
      and a switch from CD8(+)11b(+) to CD8(+)11. All cancer patients were supervised
      for up to 19 months, the period corresponding to minimum survival of glioblastoma
      patients. The obtained results have permitted to specify the common criteria for
      "anti-IGF-I" strategy: characteristics sine qua non of injected "vaccines"
      (cloned cells IGF-I(-) and MHC-I(+)) and of PBL cells (CD8(+) increased level).

PMID- 22400113
TI  - Sphingolipid and ceramide homeostasis: potential therapeutic targets.
AB  - Sphingolipids are ubiquitous in eukaryotic cells where they have been attributed
      a plethora of functions from the formation of structural domains to polarized
      cellular trafficking and signal transduction. Recent research has identified and
      characterised many of the key enzymes involved in sphingolipid metabolism and
      this has led to a heightened interest in the possibility of targeting these
      processes for therapies against cancers, Alzheimer's disease, and numerous
      important human pathogens. In this paper we outline the major pathways in
      eukaryotic sphingolipid metabolism and discuss these in relation to disease and
      therapy for both chronic and infectious conditions.

PMID- 22400114
TI  - ER Stress and Lipid Metabolism in Adipocytes.
AB  - The role of endoplasmic reticulum (ER) stress is a rapidly emerging field of
      interest in the pathogenesis of metabolic diseases. Recent studies have shown
      that chronic activation of ER stress is closely linked to dysregulation of lipid
      metabolism in several metabolically important cells including hepatocytes,
      macrophages, beta-cells, and adipocytes. Adipocytes are one of the major cell
      types involved in the pathogenesis of the metabolic syndrome. Recent advances in
      dissecting the cellular and molecular mechanisms involved in the regulation of
      adipogenesis and lipid metabolism indicate that activation of ER stress plays a
      central role in regulating adipocyte function. In this paper, we discuss the
      current understanding of the potential role of ER stress in lipid metabolism in
      adipocytes. In addition, we touch upon the interaction of ER stress and autophagy
      as well as inflammation. Inhibition of ER stress has the potential of decreasing
      the pathology in adipose tissue that is seen with energy overbalance.

PMID- 22400115
TI  - Hyaluronan regulates cell behavior: a potential niche matrix for stem cells.
AB  - Hyaluronan is a linear glycosaminoglycan that has received special attention in
      the last few decades due to its extraordinary physiological functions. This
      highly viscous polysaccharide is not only a lubricator, but also a significant
      regulator of cellular behaviors during embryogenesis, morphogenesis, migration,
      proliferation, and drug resistance in many cell types, including stem cells. Most
      hyaluronan functions require binding to its cellular receptors CD44, LYVE-1,
      HARE, layilin, and RHAMM. After binding, proteins are recruited and messages are
      sent to alter cellular activities. When low concentrations of hyaluronan are
      applied to stem cells, the proliferative activity is enhanced. However, at high
      concentrations, stem cells acquire a dormant state and induce a multidrug
      resistance phenotype. Due to the influence of hyaluronan on cells and tissue
      morphogenesis, with regards to cardiogenesis, chondrogenesis, osteogenesis, and
      neurogenesis, it is now been utilized as a biomaterial for tissue regeneration.
      This paper summarizes the most important and recent findings regarding the
      regulation of hyaluronan in cells.

PMID- 22400116
TI  - Increased Urine IgM and IgG(2) Levels, Indicating Decreased Glomerular Size
      Selectivity, Are Not Affected by Dalteparin Therapy in Patients with Type 2
      Diabetes.
AB  - Fifty-four type 2 diabetic patients with neuroischemic foot ulcers were
      randomised to treatment with 5000 IU of dalteparin, (n = 28), or physiological
      saline, (n = 26), once daily until ulcer healing or for a maximum of 6 months.
      Thirty-three patients had normo-, 15 micro-, and 6 macroalbuminuria. The urinary
      levels of IgM and IgG(2) were elevated in 47 and 50 patients, respectively.
      Elevated urinary levels of IgM and IgG(2) indicate decreased glomerular size
      selectivity. Urine IgM levels were associated with IGF-1/IGFBP-1 and IGFBP-1
      levels. Dalteparin treatment increased urinary levels of glycosaminoglycans (P <
      0.001) and serum IGFBP-1 (P < 0.05) while no significant effects were seen in any
      of the other studied parameters. In conclusion, dalteparin therapy in patients
      with type 2 diabetes had no effects on urinary levels of albumin, IgM, or IgG(2)
      despite significantly increased glycosaminoglycans in urine. Elevated urinary
      levels of IgM and IgG(2) might be more sensitive markers of renal disease than
      albuminuria in patients with type 2 diabetes and antihypertensive therapy.

PMID- 22400117
TI  - The oxidative function of diferric transferrin.
AB  - There is evidence for an unexpected role of diferric transferrin as a terminal
      oxidase for the transplasma membrane oxidation of cytosolic NADH. In the original
      studies which showed the reduction of iron in transferrin by the plasma membranes
      NADH oxidase, the possible role of the reduction on iron uptake was emphasized.
      The rapid reoxidation of transferrin iron under aerobic conditions precludes a
      role for surface reduction at neutral pH for release of iron for uptake at the
      plasma membrane. The stimulation of cytosolic NADH oxidation by diferric
      transferrin indicates that the transferrin can act as a terminal oxidase for the
      transplasma membrane NADH oxidase or can bind to a site which activates the
      oxidase. Since plasma membrane NADH oxidases clearly play a role in cell
      signaling, the relation of ferric transferrin stimulation of NADH oxidase to cell
      control should be considered, especially in relation to the growth promotion by
      transferrin not related to iron uptake. The oxidase can also contribute to
      control of cytosolic NAD concentration, and thereby can activate sirtuins for
      control of ageing and growth.

PMID- 22400119
TI  - DNA Damage Protecting Activity and Free Radical Scavenging Activity of
      Anthocyanins from Red Sorghum (Sorghum bicolor) Bran.
AB  - There is increasing interest in natural food colorants like carotenoids and
      anthocyanins with functional properties. Red sorghum bran is known as a rich
      source for anthocyanins. The anthocyanin contents extracted from red sorghum bran
      were evaluated by biochemical analysis. Among the three solvent system used, the
      acidified methanol extract showed a highest anthocyanin content (4.7 mg/g of
      sorghum bran) followed by methanol (1.95 mg/g) and acetone (1 mg/g). Similarly,
      the highest total flavonoids (143 mg/g) and total phenolic contents (0.93 mg/g)
      were obtained in acidified methanol extracts than methanol and acetone extracts.
      To study the health benefits of anthocyanin from red sorghum bran, the total
      antioxidant activity was evaluated by biochemical and molecular methods. The
      highest antioxidant activity was observed in acidified methanol extracts of
      anthocyanin in dose-dependent manner. The antioxidant activity of the red sorghum
      bran was directly related to the total anthocyanin found in red sorghum bran.

PMID- 22400120
TI  - The biomechanics of cervical spondylosis.
AB  - Aging is the major risk factor that contributes to the onset of cervical
      spondylosis. Several acute and chronic symptoms can occur that start with neck
      pain and may progress into cervical radiculopathy. Eventually, the degenerative
      cascade causes desiccation of the intervertebral disc resulting in height loss
      along the ventral margin of the cervical spine. This causes ventral angulation
      and eventual loss of lordosis, with compression of the neural and vascular
      structures. The altered posture of the cervical spine will progress into kyphosis
      and continue if the load balance and lordosis is not restored. The content of
      this paper will address the physiological and biomechanical pathways leading to
      cervical spondylosis and the biomechanical principles related to the surgical
      correction and treatment of kyphotic progression.

PMID- 22400118
TI  - At the Start of the Sarcomere: A Previously Unrecognized Role for Myosin
      Chaperones and Associated Proteins during Early Myofibrillogenesis.
AB  - The development of striated muscle in vertebrates requires the assembly of
      contractile myofibrils, consisting of highly ordered bundles of protein
      filaments. Myofibril formation occurs by the stepwise addition of complex
      proteins, a process that is mediated by a variety of molecular chaperones and
      quality control factors. Most notably, myosin of the thick filament requires
      specialized chaperone activity during late myofibrillogenesis, including that of
      Hsp90 and its cofactor, Unc45b. Unc45b has been proposed to act exclusively as an
      adaptor molecule, stabilizing interactions between Hsp90 and myosin; however,
      recent discoveries in zebrafish and C. elegans suggest the possibility of an
      earlier role for Unc45b during myofibrillogenesis. This role may involve
      functional control of nonmuscle myosins during the earliest stages of myogenesis,
      when premyofibril scaffolds are first formed from dynamic cytoskeletal actin.
      This paper will outline several lines of evidence that converge to build a model
      for Unc45b activity during early myofibrillogenesis.

PMID- 22400121
TI  - Haemodynamic monitoring using echocardiography in the critically ill: a review.
AB  - Physicians caring for the critically ill are now expected to acquire competence
      in echocardiography. It has become an indispensable diagnostic and monitoring
      tool in acute care settings where it is generally accepted to have therapeutic
      impact. There are a number of indications for a critical care echocardiographic
      study, and the most important queries include those pertaining left and right
      ventricular function and filling status. Focused examinations are increasing in
      popularity and provide a means for systematic study, and can be easily learned
      and practiced by novices. This paper addresses the indications, therapeutic
      impact, and some of the most common questions that can be answered using
      echocardiography the in critically ill patient.

PMID- 22400122
TI  - Myocardial restoration: is it the cell or the architecture or both?
AB  - Myocardial infarction is the leading cause of death in developed countries.
      Cardiac cell therapy has been introduced to clinical trials for more than ten
      years but its results are still controversial. Tissue engineering has addressed
      some limitations of cell therapy and appears to be a promising solution for
      cardiac regeneration. In this review, we would like to summarize the current
      understanding about the therapeutic effect of cell therapy and tissue engineering
      under purview of functional and structural aspects, highlighting actual roles of
      each therapy towards clinical application.

PMID- 22400123
TI  - Clinical applications of remote ischemic preconditioning.
AB  - Ischemia-reperfusion injury is a composite of damage accumulated during reduced
      perfusion of an organ or tissue and the additional insult sustained during
      reperfusion. Such injury occurs in a wide variety of clinically important
      syndromes, such as ischemic heart disease and stroke, which are responsible for a
      high degree of morbidity and mortality worldwide. Basic research has identified a
      number of interventions that stimulate innate resistance of tissues to ischemia
      reperfusion injury. Here, we summarise the experimental and clinical trial data
      underpinning one of these "conditioning" strategies, the phenomenon of remote
      ischemic preconditioning.

PMID- 22400124
TI  - Genomic research to identify novel pathways in the development of abdominal
      aortic aneurysm.
AB  - Abdominal aortic aneurysm (AAA) is a common disease with a large heritable
      component. There is a need to improve our understanding of AAA pathogenesis in
      order to develop novel treatment paradigms. Genomewide association studies have
      revolutionized research into the genetic variants that underpin the development
      of many complex diseases including AAA. This article reviews the progress that
      has been made to date in this regard, including mechanisms by which loci
      identified by GWAS may contribute to the development of AAA. It also highlights
      potential post-GWAS analytical strategies to improve our understanding of the
      disease further.

PMID- 22400126
TI  - Wafer Scale Integration of CMOS Chips for Biomedical Applications via Self
      Aligned Masking.
AB  - This paper presents a novel technique for the integration of small CMOS chips
      into a large area substrate. A key component of the technique is the CMOS chip
      based self-aligned masking. This allows for the fabrication of sockets in wafers
      that are at most 5 um larger than the chip on each side. The chip and the large
      area substrate are bonded onto a carrier such that the top surfaces of the two
      components are flush. The unique features of this technique enable the
      integration of macroscale components, such as leads and microfluidics.
      Furthermore, the integration process allows for MEMS micromachining after CMOS
      die-wafer integration. To demonstrate the capabilities of the proposed
      technology, a low-power integrated potentiostat chip for biosensing implemented
      in the AMI 0.5 um CMOS technology is integrated in a silicon substrate. The
      horizontal gap and the vertical displacement between the chip and the large area
      substrate measured after the integration were 4 um and 0.5 um, respectively. A
      number of 104 interconnects are patterned with high-precision alignment.
      Electrical measurements have shown that the functionality of the chip is not
      affected by the integration process.

PMID- 22400127
TI  - Highly sensitive detection of protein and small molecules based on aptamer
      modified electrochemiluminescence nanoprobe.
AB  - Amplified optical detection of biomolecules using nanoparticle as the carrier has
      attracted considerable interest in the scientific community. In this study, a
      promising aptasensor was developed for highly sensitive detection of protein and
      small molecules based on the construction of aptamer-modified
      electrochemiluminescence (ECL) nanoprobe. Specifically, thrombin and ATP serve as
      the examples for detection. By taking advantage of sandwich binding of two
      affinity aptamers for high specificity, tris-(2,2'-bipyridyl)ruthenium (TBR)
      cysteamine loaded in gold nanoparticle (GNP) as barcodes for signal
      amplification, and micromagnetic particles (MMPs) based ECL technology for rapid
      detection, a novel assay for biomolecules quantification was developed. The
      sandwich complex containing targets could be selectively captured by MMPs and
      then quantified by ECL intensity. We have demonstrated that the detection limits
      of human thrombin and ATP are 1 pM and 10 pM, respectively, with high
      specificity. The proposed technology is expected to become a powerful tool for
      biomolecule analysis.

PMID- 22400128
TI  - Systems biology: design principles of whole biological systems. Preface.

PMID- 22400125
TI  - Vascular Dysfunction in Brain Hemorrhage: Translational Pathways to Developing
      New Treatments from Old Targets.
AB  - Hemorrhagic stroke which is a form of stroke that affects 20% of all stroke
      patients is a devastating condition for which new treatments must be developed.
      Current treatment methods are quite insufficient to reduce long term morbidity
      and high mortality rate, up to 50%, associated with bleeding into critical brain
      structures, into ventricular spaces and within the subarachnoid space. During the
      last 10-15 years, significant advances in the understanding of important
      mechanisms that contribute to cell death and clinical deficits have been made.
      The most important observations revolve around a key set of basic mechanisms that
      are altered in brain bleeding models, including activation of membrane
      metalloproteinases, oxidative stress and both inflammatory and coagulation
      pathways. Moreover, it is now becoming apparent that brain hemorrhage can
      activate the ischemic stroke cascade in neurons, glial cells and the vascular
      compartment. The activation of multiple pathways allows comes the opportunity to
      intervene pharmacologically using monotherapy or combination therapy. Ultimately,
      combination therapy or pleiotropic compounds with multi-target activities should
      prove to be more efficacious than any single therapy alone. This article provides
      a comprehensive look at possible targets for small molecule intervention as well
      as some new approaches that result in metabolic down-regulation or inhibition of
      multiple pathways simultaneously.

PMID- 22400129
TI  - When conflicted becomes corrupted II--the Molette doctrine. By Caveman.

PMID- 22400130
TI  - Advanced X-ray crystallography. Preface.

PMID- 22400131
TI  - Managing wastewater from fracking, with Robert B. Jackson by Ahearn Ashley.

PMID- 22400132
TI  - [The error as friend].

PMID- 22400140
TI  - Has anyone seen it? Health care in Croatian elections.
AB  - Over the past decade, public opinion surveys have shown that Croats are deeply
      dissatisfied with their health care system and asses it to be one of the most
      important issues. However, health care hardly makes it into any political
      discourse in Croatia. This study analyzes the results of a public opinion survey
      conducted before the 2007 parliamentary elections to find out what the public
      sentiment on health care performance in Croatia is and to analyze the reasons why
      health care is not addressed by political actors. Evidence suggests that while
      health care is the most salient issue today, the public often understands it
      poorly. Thus, in a political environment of competing issues, and given the
      complexity of tacking health care in the policy arena, politicians strategically
      avoid discussing the issue.

PMID- 22400141
TI  - Biology, ideology, and epistemology: how do we know political attitudes are
      inherited and why should we care?
AB  - Evidence that political attitudes and behavior are in part biologically and even
      genetically instantiated is much discussed in political science of late. Yet the
      classic twin design, a primary source of evidence on this matter, has been
      criticized for being biased toward finding genetic influence. In this article, we
      employ a new data source to test empirically the alternative, exclusively
      environmental, explanations for ideological similarities between twins. We find
      little support for these explanations and argue that even if we treat them as
      wholly correct, they provide reasons for political science to pay more rather
      than less attention to the biological basis of attitudes and behaviors. Our
      analysis suggests that the mainstream socialization paradigm for explaining
      attitudes and behaviors is not necessarily incorrect but is substantively
      incomplete.

PMID- 22400142
TI  - Correlation not causation: the relationship between personality traits and
      political ideologies.
AB  - The assumption in the personality and politics literature is that a person's
      personality motivates them to develop certain political attitudes later in life.
      This assumption is founded on the simple correlation between the two constructs
      and the observation that personality traits are genetically influenced and
      develop in infancy, whereas political preferences develop later in life. Work in
      psychology, behavioral genetics, and recently political science, however, has
      demonstrated that political preferences also develop in childhood and are equally
      influenced by genetic factors. These findings cast doubt on the assumed causal
      relationship between personality and politics. Here we test the causal
      relationship between personality traits and political attitudes using a direction
      of causation structural model on a genetically informative sample. The results
      suggest that personality traits do not cause people to develop political
      attitudes; rather, the correlation between the two is a function of an innate
      common underlying genetic factor.

PMID- 22400143
TI  - Polarizing cues.
AB  - People categorize themselves and others, creating ingroup and outgroup
      distinctions. In American politics, parties constitute the in- and outgroups, and
      party leaders hold sway in articulating party positions. A party leader's
      endorsement of a policy can be persuasive, inducing co-partisans to take the same
      position. In contrast, a party leader's endorsement may polarize opinion,
      inducing out-party identifiers to take a contrary position. Using survey
      experiments from the 2008 presidential election, I examine whether in- and out
      party candidate cues-John McCain and Barack Obama-affected partisan opinion. The
      results indicate that in-party leader cues do not persuade but that out-party
      leader cues polarize. This finding holds in an experiment featuring President
      Bush in which his endorsement did not persuade Republicans but it polarized
      Democrats. Lastly, I compare the effect of party leader cues to party label cues.
      The results suggest that politicians, not parties, function as polarizing cues.

PMID- 22400144
TI  - The complications of controlling agency time discretion: FDA review deadlines and
      postmarket drug safety.
AB  - Public agencies have discretion on the time domain, and politicians deploy
      numerous policy instruments to constrain it. Yet little is known about how
      administrative procedures that affect timing also affect the quality of agency
      decisions. We examine whether administrative deadlines shape decision timing and
      the observed quality of decisions. Using a unique and rich dataset of FDA drug
      approvals that allows us to examine decision timing and quality, we find that
      this administrative tool induces a piling of decisions before deadlines, and that
      these "just-before-deadline" approvals are linked with higher rates of postmarket
      safety problems (market withdrawals, severe safety warnings, safety alerts).
      Examination of data from FDA advisory committees suggests that the deadlines may
      impede quality by impairing late-stage deliberation and agency risk
      communication. Our results both support and challenge reigning theories about
      administrative procedures, suggesting they embody expected control-expertise
      trade-offs, but may also create unanticipated constituency losses.

PMID- 22400145
TI  - Welfare policymaking and intersections of race, ethnicity, and gender in U.S.
      state legislatures.
AB  - Welfare policy in the American states has been shaped profoundly by race,
      ethnicity, and representation. Does gender matter as well? Focusing on state
      welfare reform in the mid-1990s, we test hypotheses derived from two alternative
      approaches to incorporating gender into the study of representation and welfare
      policymaking. An additive approach, which assumes gender and race/ethnicity are
      distinct and independent, suggests that female state legislators-regardless of
      race/ethnicity-will mitigate the more restrictive and punitive aspects of welfare
      reform, much like their African American and Latino counterparts do. In contrast,
      an intersectional approach, which highlights the overlapping and interdependent
      nature of gender and race/ethnicity, suggests that legislative women of color
      will have the strongest countervailing effect on state welfare reform-stronger
      than that of other women or men of color. Our empirical analyses suggest an
      intersectional approach yields a more accurate understanding of gender,
      race/ethnicity, and welfare politics in the states.

PMID- 22400149
TI  - Creating an enabling environment for diasporas' participation in homeland
      development.
AB  - Diasporas contribute to their homeland's development through remittances,
      philanthropy, skills transfer, business investment, and advocacy. This paper
      focuses on actions that homeland governments can take to create an enabling
      environment for diasporas' contributions. Part I addresses the diaspora
      phenomenon and the homeland government-diaspora relationship. Part II develops a
      framework for characterizing government's role in an enabling environment
      specific to diasporas' development contributions. Part III considers how to put
      the framework into practice, identifying important caveats and discussing several
      implementation issues, including the potential role of donors. The framework is
      also a tool for diasporans to strategically advocate for improved enabling
      environments.

PMID- 22400153
TI  - From biodefence to biosecurity: the Obama administration's strategy for
      countering biological threats.
AB  - The Seventh Review Conference of the Biological Weapons Convention (BWC), the
      first international treaty to outlaw an entire class of weapons, was held in
      Geneva in December 2011. On 7 December, Secretary of State Hillary Clinton became
      the highest-ranking US government official to address a BWC meeting. Secretary
      Clinton told the assembled delegation that 'we view the risk of bioweapons attack
      as both a serious national security challenge and a foreign policy priority'. At
      the same time, she warned that a large-scale disease outbreak 'could cripple an
      already fragile global economy'. Secretary Clinton's speech reflected a new
      understanding that the range of biological threats to international security has
      expanded from state-sponsored biological warfare programmes to include biological
      terrorism, dual-use research and naturally occurring infectious diseases such as
      pandemics. Recognizing these changes, President Barack Obama released a new
      national strategy for countering biological threats in 2009. This strategy
      represents a shift in thinking away from the George W. Bush administration's
      focus on biodefence, which emphasized preparing for and responding to biological
      weapon attacks, to the concept of biosecurity, which includes measures to
      prevent, prepare for and respond to naturally occurring and man-made biological
      threats. The Obama administration's biosecurity strategy seeks to reduce the
      global risk of naturally occurring and deliberate disease outbreaks through
      prevention, international cooperation, and maximizing synergies between health
      and security. The biosecurity strategy is closely aligned with the Obama
      administration's broader approach to foreign policy, which emphasizes the
      pragmatic use of smart power, multilateralism and engagement to further the
      national interest. This article describes the Obama administration's biosecurity
      strategy; highlights elements of continuity and change from the policies of the
      Bush administration; discusses how it fits into Obama's broader foreign policy
      agenda; and analyses critical issues that will have to be addressed in order to
      implement the strategy successfully.

PMID- 22400154
TI  - Using GIS and perceived distance to understand the unequal geographies of
      healthcare in lower-income urban neighbourhoods.
AB  - Geographers play important roles in public health research, particularly in
      understanding healthcare accessibility, utilisation, and individual healthcare
      experiences. Most accessibility studies have benefited from the increased
      sophistication of geographic information systems (GIS). Some studies have been
      enhanced with semi-structured in-depth interviews to understand individual
      experiences of people as they access healthcare. However, few accessibility
      studies have explicitly utilised individual in-depth interview data in the
      construction of new GIS accessibility measures. Using mixed methods including GIS
      analysis and individual data from semi-structured in-depth interviews, we offer
      satisfaction-adjusted distance as a new way of conceptualising accessibility in
      GIS. Based on fieldwork in a predominantly lower-income community in Columbus,
      Ohio (USA), we find many residents felt neighbourhood healthcare facilities
      offered low-quality care, which suggested an added perceived distance as they
      attempt to access high-quality healthcare facilities. The satisfaction-adjusted
      distance measure accounts for the perceived distance some residents feel as they
      search for high-quality healthcare in lower-income urban neighbourhoods. In
      moving beyond conventional GIS and re-conceptualising accessibility in this way,
      we offer a more realistic portrayal of the issues lower-income urban residents
      face as they attempt to access high-quality healthcare facilities. The work has
      theoretical implications for conceptualising healthcare accessibility, advances
      the mixed-methodologies literature, and argues for a more equitable distribution
      of high-quality healthcare in urban neighbourhoods.

PMID- 22400155
TI  - Women and children first? The administration of Titanic relief in Southampton,
      1912-59.
AB  - One of the principal narratives woven around the 1912 sinking of the Titanic is
      that the tragedy united people around the world in a shared sense of horror and
      grief. This study examines the administration of the relief fund collected for
      victims and questions the established image of social unity and collective
      suffering. The records of the Southampton Titanic Relief Fund reveal welfare
      processes imbued with class and gender prejudices that consigned many of the
      relatives of victims to poverty-stricken lives, despite the massive fund
      collected in their names.

PMID- 22400156
TI  - Popular culture and sporting life in the rural margins of late eighteenth-century
      England: the world of Robert Anderson, "The Cumberland Bard".
AB  - This study sets out to extend and challenge existing historiography on late
      eighteenth century British popular culture, customary sports, class and cultural
      identity, focusing upon the rural geo-political borderland of England. It
      suggests that prevailing class-based and more London-biased studies need to be
      balanced with more regionalist-based work, and shows the importance of northern
      regional leisure variants. The textual and historical analysis draws largely on
      the published works of a neglected working-class dialect poet, Robert Anderson,
      living and working in Cumberland, arguing that he represented a strain of
      ''bardic regionalism,'' a variant of Katie Trumpener's ''bardic nationalism.''

PMID- 22400157
TI  - Unbending the mind: or, commercialized leisure and the rhetoric of eighteenth
      century diversion.
AB  - This essay opens by asking why the formative period in the "commercialization of
      leisure" in England (c. 1690-1760) happens also to be the period during which
      intrusion, obstruction, and interruption first began to thrive as conspicuous
      rhetorical techniques in commercial literature. The essay answers this question
      through a series of close readings that reveal the complex reciprocity between
      what I call "cultural diversion" and "discursive diversion," between those social
      amusements which provide relief from the serious concerns of daily life and those
      linguistic and textual devices which characteristically disrupt so much of the
      discourse of the late seventeenth and early eighteenth century-devices such as
      extravagant metaphors, rows of asterisked ellipses, and, most pervasively,
      digressions. Where modern discussion of such devices has tended to rely on the
      critical touch-stone of "self-consciousness," this essay restores disruptive
      rhetoric to what I see as its original cultural context by demonstrating how
      frequently self-conscious authors associate the form and function of devices like
      digression with London's "Reigning Diversions."

PMID- 22400158
TI  - Steve Jobs's cancer.  Pancreatic neuroendocrine tumors are becoming more common
      (the bad news) and also more treatable (the good news).

PMID- 22400159
TI  - What is it about coffee?  Research is showing benefits for everything from
      depression to liver disease.  Is it just the caffeine?

PMID- 22400160
TI  - Talking about migraine.

PMID- 22400161
TI  - Try yoga for back pain (but talk to your doctor first).

PMID- 22400162
TI  - Watch out for medical identity theft.

PMID- 22400163
TI  - Tea and coffee with your fish?

PMID- 22400164
TI  - Coldhearted is not healthy.

PMID- 22400165
TI  - Ask the doctor.  I take Avodart for my enlarged prostate.  But I heard that
      Avodart increases prostate cancer risk.  Is that true?  Should I quit taking
      Avodart?

PMID- 22400166
TI  - Quo vadis. 1961.

PMID- 22400167
TI  - Long-term care: funding of long-term care.

PMID- 22400168
TI  - Telemedicine: a technology in waiting.

PMID- 22400169
TI  - Food security bill and the failings of the debate around it.

PMID- 22400170
TI  - ACAPN Division News: changes and opportunities.

PMID- 22400171
TI  - [Post-traumatic stress].
AB  - As civilization advanced, the number of disasters, including their types and size
      of the threat to humanity. In addition to natural disasters and wars, there are
      currently a disaster communication, environmental and technological. Disasters
      "new generation" include increasingly frequent bombings and terrorist attacks.
      These events are an impediment to long-lasting and deep impact on the mental
      functioning of the victims of the event. This represents a potential risk of a
      variety of psychopathological symptoms, which go beyond the limits of human
      suffering. ICD-I0 classification includes individuals sickness arising as a
      consequence of pathological after surviving the disaster, which include: acute
      stress disorder (ASD), post-traumatic stress disorder (PTSD), post-traumatic
      stress disorder linked to depression, symptoms anxiety, addictions, dissociative
      disorders and personality changes and permanent after the disaster.

PMID- 22400172
TI  - [Change of quality of life and NYHA class in patients with advanced heart failure
      and permanent atrial fibrillation after 12-months period from upgrade of pacing
      system].
AB  - There is no research on the change of quality of life and NYHA classification
      after pacing system upgrade performed as a treatment of advanced heart failure
      during a long observation period in a particular population of patients with long
      term apical right ventricular pacing, permanent atrial fibrillation and complete
      atrio-ventricular block. The aim of the study was evaluation of changes in
      quality of life and NYHA class in group of patients in which upgrade from right
      ventricular apical pacing to biventricular or bifocal right ventricular pacing
      was done. MATERIAL AND METHODS: Evaluation of quality of life was performed in a
      chosen group of 27 patients (20 males, mean age 71.2) who completed the 12-month
      observation period. Quality of life was assessed by the Short Form-36 (SF-36)
      questionnaire. The first examination was carried out before the planned pacing
      system upgrade, that is, when advanced heart failure appeared in the course of
      permanent atrial fibrillation and right ventricular apical pacing present for a
      long time (on average 7.7 years). The change of quality of life after 12-month
      period of upgrade pacing system was analyzed. A comparison of patient's self
      assessment (as far as physical aspect of quality of life is concerned - Physical
      Component Summary - PCS) with doctor's interview concerning NYHA classification
      was performed. Additionally quality of life pointed out by a patient was analyzed
      in relation to the diseases most common in this population: hypertension,
      diabetes mellitus and renal failure. Because the questionnaires were completed by
      the patients personally without the third party, the assessment referred to
      mistakes in filling in the questionnaires (quantity of missed questions and
      incorrect marking the answers by adding individual comments) in relation to
      patients' age. RESULTS: In 12-month follow-up after pacing system upgrade,
      improvement of quality of life was found in 48.1% of patients. Assessment of
      physical aspect of quality of life was possible due to SF-36. Improvement
      occurred in 55.5% of patients, however in relation with NYHA classification
      improvement appeared in 51.8% of patients. Improvement in NYHA was in significant
      correlation with improvement in physical aspect of life (p = 0.025), especially
      in the subgroup treated by pacing system upgrade to bifocal right ventricular
      pacing (p = 0.0066). In the subgroup with improvement, hypertension and diabetes
      were less frequent, however frequency of renal failure was greater, than in the
      subgroup without quality of live improvement. Both before and after pacing system
      upgrade, there was no significant connection (only a trend) between the number of
      mistakes done during self-completion of the questionnaires and patients' age.
      CONCLUSIONS: In 12-month follow-up after pacing system upgrade, improvement of
      quality of life was found in 48.1% of patients. There exists a significant
      correlation between the improvement of physical efficiency in NYHA class and the
      improvement in physical aspect of quality of life in patients' self assessment (p
      = 0.025). In the subgroup treated by pacing system upgrade to bifocal right
      ventricular pacing this correlation is especially strong (p = 0.0066).

PMID- 22400173
TI  - [The interdependence of coronary pain control and level of anxiety in women with
      ischiaemic heart disease].
AB  - Interdependences between pain and anxiety in cardiac ischaemia are
      multidimensional and complex. Both of these phenomena share a lot of traits and
      they tend to reinforce each other at physiological level. Apart from arduousness
      of pain, cognitive understanding of its nature becomes an important mediating
      factor. One of important characteristics of the patient's attitude towards their
      illness is localization of pain control. The aim of the study was to analyze an
      interdependence between an anxiety as a state and as a trait and the localization
      of pain control in women with coronary heart decease. MATERIAL AND METHODS: The
      study included 52 female patients hospitalised at The Department of Cardiology of
      The Medical University of Lublin who underwent coronarography. The used methods
      included an interview, State - Trait Anxiety Inventory of Spielberger (STAI) and
      The Beliefs about Pain Control Questionnaire (BPCQ). RESULTS: The results did not
      confirm an often suggested opinion that internal localization of pain control
      reduces anxiety and activates the patient. The intensity of the internal
      localization of pain control correlates significantly with the intensity of the
      dependence of pain of activity of the doctors as well as on the anxiety as trait.
      It is higher in women with lower education. Perhaps better educated patients, not
      so ready to react with anxiety, can treat pain more realistically as a sign of a
      pathological process which can be understood and evaluated not so much as a
      catastrophe. They do not feel personally responsible for the pain, either, and
      are able to accept the limits of the doctor's assistance, having no unrealistic
      expectations with regard to the pain treatment. CONCLUSIONS: The results of the
      research indicate that in women with ischiaemic heart decease better adjustment
      to the illness and a lower level of anxiety as a trait are connected with the
      understanding and acceptance of their situation by the patient, rather than with
      too big extent of expectations towards the control of pain by the patients
      themselves or medical staff.

PMID- 22400174
TI  - [Exercise testing to estimate dysfunction of the autonomic nervous system in
      subjects with carbohydrate disorders].
AB  - Slow heart rate recovery (HRR) 2 minutes after exercise testing is a predictor of
      cardiovascular mortality and index of decreased parasympathetic activity. The aim
      of the study was to evaluate the heart rate recovery in subjects with
      carbohydrate disorders. MATERIAL AND METHODS: The study comprised 112 subjects
      with carbohydrate disorders (54 females and 58 males), aged 30-78 (57.4 +/- 9.6)
      years. Carbohydrate disorders were diagnosed according to the Polish Diabetes
      Association criteria from 2007 (group I). 56 subjects had impaired fasting
      glucose (IFG), 36 - impaired glucose tolerance (IGT) and 20 - type 2 diabetes.
      Comparative group comprised 30 subjects without cardiovascular diseases and
      carbohydrate disorders (15 females and 15 males), aged 29-64 (52.70 +/- 8.8)
      years (group II). The fasting serum glucose level was evaluated using an
      enzymatic method, Kone-Pro biochemical analyzer and bioMerieux Glucose RTU kit.
      In subjects with fasting glucose level > or = 100 mg/dl, an oral glucose
      tolerance test (OGTT) was performed. In all subjects submaximal exercise
      treadmill testing was performed. Heart rate recovery was defined as a difference
      between the peak heart rate and that after 2 minutes of recovery in sitting
      position. RESULTS: In subjects with carbohydrate disorders the mean value of HRR
      was 38.93 +/- 12.08/min and it was significantly lower (p < 0.05) than in
      comparative group (57.0 +/- 11.44/min). In subjects with carbohydrate disorders
      negative correlation between HRR and patients' age as well as between HRR and
      fasting glucose level in males. On the basis of ROC curve analysis and OR (odds
      ratio) it was shown that HRR < or = 43.5/min results in almost threefold
      increased risk of carbohydrate disorders. CONCLUSIONS: In subjects with
      carbohydrate disorders the value of HRR is lowered, what stands for decreased
      parasympathetic activity and increased cardiovascular risk. HRR < or = 43.5/min
      results in almost threefold increased risk of carbohydrate disorders.

PMID- 22400175
TI  - [The prognostic role of clinical factors, VEGF, IL-8 and sTNF-R1 in cutaneous
      melanomas at locoregional stage].
AB  - The treatment results of patients with locoregional melanoma are still not
      satisfactory - up to 50% of patients experience recurrence and (or) disease
      dissemination. The aim of the study was to assess the prognostic value of
      clinical factors and serum cytokines of patients with cutaneous melanoma in
      locoregional stage. MATERIAL AND METHODS: 149 patients at stage I-III according
      AJCC treated between 2007-2010 were included. Pre-surgery serum levels of VEGF IL
      8 and sTNF-R1 were analyzed by ELISA method in 74 melanoma patients and 50
      healthy controls. The median follow-up time was 16 months (range: 1-81 months).
      RESULTS: The most important factors influencing the disease-free survival (DFS)
      are: staging system according to AJCC) (p < 0.001), regional nodal stage (pN) (p
      < 0.001), primary tumor (Breslow) thickness (pT) (p = 0.013) and melanoma
      ulceration (p = 0.004). The serum levels of selected cytokines were significantly
      higher in melanoma patients than in healthy volunteers (VEGF, p < 0.001; sTNF-R1,
      p < 0.001; IL-8, p = 0.001). There were no significant relationships between
      level of cytokine, recurrence or clinical/pathological parameters. CONCLUSIONS:
      The AJCC staging system gives the most accurate insight into prognosis of
      melanoma patients at locoregional stage after primary therapy. Cytokine serum
      profile in melanoma patients at locoregional stage has limited value for
      predicting tumor burden and treatment outcomes.

PMID- 22400176
TI  - [A catamnestic study of psychiatric consultations of patients with somatic
      diseases].
AB  - The aim of the study was to analyse diagnoses made during psychiatric
      consultations in somatic wards of the multi-profile hospital, as well as the
      catamnestic analysis of their causes and determinants. The authors intended to
      estimate the needs for psychiatric consultations in a multi-profile hospital, to
      analyse a growth or decrease in demand for psychiatric consultations within two
      years, the analysis of psychiatric diagnoses made in the course of consultations
      qualifying a patient for transfer to the psychiatric clinic. MATERIAL AND
      METHODS: Personal experience from work as a consultant psychiatrist as well as
      data from the literature were used in the study. The collected research material
      in the form of psychiatric consultations concerned the case histories of the
      Archive of the 10 Military Clinical Hospital with Polyclinic in Bydgoszcz from
      2006-2007. A total of 735 consultations in 630 patients were carried out.
      RESULTS: The results of the study indicated that in a multi-profile hospital
      there is a great demand for psychiatric consultations. The most frequent cause of
      reporting the need for consultation by doctors in somatic wards were depressive
      disorders. The results obtained also showed that the fact of alcohol intoxication
      at admission is an important factor which can potentially have an effect on the
      need for a psychiatric consultation as well as a later decision to transfer the
      patient to other hospital departments. Additional psychological consultations
      commissioned in patients moved to psychiatric clinic were carried out in an
      amount higher than average, and the largest number of them were carried out among
      those refusing the transfer. CONCLUSIONS: The most often diagnoses made during
      consultations were: dysphoria and affective disorders secondary to organic
      changes, adaptive disorders and delirium.

PMID- 22400177
TI  - [Symbolizm of medical institutions].
AB  - Marketing in health service has become an indispensable tool for creating and
      maintaining a positive image of medical institutions which to a great extent
      determines their success on the market. This process entails not only providing
      professional, reliable and up-to-date patient care but also establishing good
      reputation among those who already use it and its potential customers. It should
      be recognizable also for deliverers, investors, competitors, media and
      particularly for society and local authorities. The key to success is
      professionalism of personnel and their identification with the mission of the
      institution and the direction of changes being implemented there. For a complete
      success and recognition is essential health care facilities, which affects
      virtually matched the name and symbol, and communication of people responsible
      for contact with the media.

PMID- 22400178
TI  - [The essence of doctor-patient relationship in creating image of a medical
      institution].
AB  - Irrespective of changing standards and continuous reforms in health service, the
      patient should always remain the principal focus. The patient is a person who
      should be treated not only as a customer or a recipient of medical services but
      also as a person being in a situation which is difficult and often unacceptable.
      Among the factors affecting patients' satisfaction and contentment in the course
      of the disease it is profoundly important that he cooperates with his doctor. For
      years it has been attempted to create an ideal model of doctor-patient
      relationship which would be mutually beneficial and not violating privacy or
      welfare of any of them. These attempts focused on various theoretical models,
      among others paternalistic, informative and interpretive. However, special
      attention should be paid to adherence to principles which is based on respect for
      patient autonomy, harmlessness, charity and fairness.

PMID- 22400179
TI  - [Research ethics committees: one size fits all?].
AB  - Till now Poland did not create an effective system which should protect rights of
      the research subjects. A research involving human subjects includes the
      observational and interventional studies. In Poland the interventional studies
      conducted by physicians or dentists must be submitted for an approval to
      bioethical committees only. There is no legal obligation to obtain an approval of
      the independent research ethics committee for all observational studies or the
      interventional studies conducted by investigators others than physicians.
      Moreover, the existing system does not demand a further monitoring of the ongoing
      studies with an exception of the clinical trials. The system of bioethics
      committees for the assessment of interventional studies conducted by physicians
      or dentists should be complemented by two types of research ethics committees:
      committees which would evaluate projects of medical studies conducted by the
      other medical specialists (for example: nurses) and committees which would
      evaluate projects of biomedical studies conducted by the non-medical specialists
      (psychologists, sociologists). The new regulations should not restrain a progress
      of the science. Thus legislators should take into the consideration that the
      projects may differ in the degree of the complexity of ethical issues and the
      scientific validity. The different methods of the assessment of the biomedical
      research projects should be available.

PMID- 22400180
TI  - [Marketing in health service--a necessity or a temporary whim?].
AB  - Permanent changes occurring in economy and politics, open borders, a greater
      number of people with higher education as well as growing social awareness
      concerning taking care of health are followed by changes in healthcare sector. In
      response to an increased social demand, new medical institutions are being
      founded. They offer their patients a vast array of services ranging from
      therapeutic to preventive and highly specialized procedures improving their
      standard of living. In order to attract regular patients, and therefore receive
      regular income, it is necessary to stabilize such institutions on services
      market. It can be achieved by numerous marketing tools which, when applied
      appropriately, enable to create a positive image of a medical institution.

PMID- 22400181
TI  - [Flavonoids in the prevention and treatment of cardiovascular diseases].
AB  - Flavonoids are plant components of the diet. Their daily intake is about 1 g. In
      Poland the main source of flavonoids is tea, apples and onions. These compounds
      are characterized by a variety of biological activities and pharmacological
      effects. Especially important for human health are their antioxidant properties.
      This paper presents the current state of knowledge on the role and importance of
      flavonoids in the prevention of the initiation and development of cardiovascular
      diseases. Epidemiological observations, clinical research, in vitro and in vivo
      experimental studies clearly show a protective effect of flavonoids on the
      cardiovascular system. Their beneficial effects on the cardiovascular system
      involve the inhibition of low density lipoprotein (LDL) oxidation, the reduction
      of blood vessels permeability, antiplatelet and anti-inflammatory activity, and
      hypotensive and direct vasodilator action. Biological potential of flavonoids
      (especially the antioxidant activity) indicates the possibility of their use in
      primary and secondary prevention of atherosclerosis and its clinical consequences
      (heart attack, stroke, and others) as a safe potential therapeutic agents.

PMID- 22400182
TI  - [Supplementation of n-3 polyunsaturated fatty acids in pulmonary disease].
AB  - N-3 polyunsaturated fatty acids, principally docosahexaenoic acid and
      eicosapentaenoic acid, present important group of fatty acids in correct diet of
      people. They have antiinflammatory, antithrombotic, antiarrythmic, hypolipidemic
      and vasodilatory properties. These beneficial effects have been shown in
      secondary prevention of coronary heart disease, hypertension, type 2 diabetes and
      in some autoimmune diseases. Carried research showed beneficial effects in
      prevention and treatment some chronic diseases of respiratory system. This paper
      sums up current reports about role of n-3 polyunsaturated fatty acids in
      prevention and treatment of some pulmonary diseases.

PMID- 22400183
TI  - [Hemophagocytic lymphohistiocytosis--a contemporary medical problem].
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of
      immnoregulation caused by various inherited and acquired factors. Uncontrolled
      activation of T lymphocytes and macrophages, together with an impaired cytotoxic
      function of NK cells, results in the massive cytokine release and
      hyperinflammatory phenotype. HLH is characterized by fever, splenomegaly and
      peripheral blood cytopenia. Cytohistological examination shows accumulation of
      lymphocytes and macrophages, sometimes with hemophagocytic activity, in different
      tissues (e.g., bone marrow). Laboratory findings include hyperferritinemia (often
      'sky-high' > 10.000 microg/l), hypertriglyceridemia, hypofibrinogenemia, and high
      levels of the alpha chain of the soluble interleukin-2 receptor (sIL-2R also
      called sCD25). In 2004 The Histiocyte Society updated current diagnostic
      guidelines for HLH. Therapy of HLH is based on suppression of the
      hyperinflammatory status by destruction of activated CD8+ T lymphocytes and
      macrophages, and treatment of any existing HLH triggers. However, treatment of
      HLH is associated with high morbidity and mortality. Therefore consideration
      should be given to referring HLH patients to centers with experience in the
      treatment and care of those with HLH. Due to aggressive course, awareness of HLH
      signs and symptoms is crucial among physicians for the early diagnosis and
      immediate introduction of adequate HLH treatment.

PMID- 22400184
TI  - [Irritable bowel syndrome--irritable bowel or irritable mind?].
AB  - Irritable bowel syndrome (IBS) is one of the most common disorders of
      gastrointestinal tract, affecting significant number of western population. The
      characteristic features are chronic and(or) recurrent abdominal pain and
      discomfort associated with changes in the bowel habit with or without bloating.
      According to Rome Criteria III there is an improved focus on the intestinal
      transit time which allows for better diagnosis and characterization of patients
      either with diarrhea, constipation predominant or mixed type IBS. Patients with
      IBS also frequently manifest various symptoms related to central nervous system
      (CNS) as depression or personality disorders. In this review we present current
      knowledge concerning etiopathogenesis of IBS with emphasis on the role of
      microbiota and describe promissing profilatic and treatment modalities with anti
      biotics and probiotics capable to modulate microbiota and gut-brain axis. Most
      recent studies concerning clinical efficacy of antibiotic rifaximin and probiotic
      strain Lactobacillus plantarum 299v in symptom prevention (reduction) of this
      common gastrointestinal disorder are briefly described.

PMID- 22400185
TI  - [Pathogenesis and clinical presentation of andropause].
AB  - In opposition to women, the age-related changes in reproductive hormones in men
      are subtle and occur gradually throughout many years of mature life. The decline
      in serum testosterone level may present as a constellation of signs and symptoms
      of hypogonadism known as "andropause". They include: loss of energy, depressed
      mood, decreased libido, erectile dysfunction, decreased muscle mass and strength,
      increased fat mass, frailty, osteopenia, and osteoporosis. Diagnosis of
      andropause is based on clinical symptoms and laboratory determinations of serum
      testosterone levels. This review summarises the present state of knowledge on the
      pathogenesis, clinical presentation as well as diagnosis of andropause.

PMID- 22400186
TI  - [Treatment of patients with andropause].
AB  - The decline in serum testosterone level occur gradually throughout men's mature
      life and it may present as a constellation of signs and symptoms of hypogonadism
      known as "andropause". When diagnosed, the treatment should be introduced. The
      benefits of testosterone supplementation in this age group have yet to be
      equivocally established. Although testosterone therapy can induce adverse
      effects, these can be largely minimised by proper monitoring. This review
      summarises the present state of knowledge on the treatment of andropause.

PMID- 22400187
TI  - [Psychological aspects of rehabilitation of the elderly people after femoral neck
      fracture].
AB  - Mobility impairments, joint deformations, osteoporosis, weakening of sensory
      functions and orientation in space, which are quite common in senility expose
      elderly individuals to various kinds of falls and accidents. Femoral neck
      fractures and pertrochanteric fractures are the most frequent traumatic injuries
      among the elderly patients. During the post-surgical period or rehabilitation
      process it is of vital importance that treatment activities should enable
      patients to function in social and family environment in the same way as before
      the accident. Furthermore, it is crucial that rehabilitation procedures be of
      multi-faceted character - owing to the psycho-physical unity of the human being,
      they should not focus merely on physical treatment of the patient, but also on
      their psychological condition which is particularly significant in the whole
      treatment process. Apart from that, it is essential to consider the level of
      anxiety and motivation of the patient and to offer them professional
      psychological support and assistance.

PMID- 22400188
TI  - [Erik Amdrup (1923-1998): The life and times of the Danish surgeon and author].
AB  - The Danish professor, surgeon, medical superintendent, researcher and writer of
      fictional literature Erik Amdrup is one of the inventors of the parietal cell
      vagotomy. He carried out many internationally acclaimed research projects about
      the surgical treatment of gastric and duodenal ulcer. At the same time he
      witnessed the changes in the conditions at the Danish hospitals. He used his
      professional experiences in his prose and his memoirs. They give an insight into
      the younger Danish history of medicine.

PMID- 22400189
TI  - [Designation of occupation and proper name--onomastical considerations on the
      early Christian inscription of Sarmanna medica from Gondorf on the River Mosel].
AB  - Some time ago, the author published some hypotheses regarding the etymological
      roots of the name Sarmanna which appears in an early Christian epitaph, which may
      be as old as the 5th century A.D. In this paper, some of these hypotheses will be
      elaborated upon, based on additional evidence in support of its eastern germanic
      origin which suggests close semantic links to medica, Sarmanna's profession. This
      kind of semantic connection seems to be unique among known ancient epitaphs. It
      thus offers important sociological and historical evidence for processes of
      acculturation and assimilation also in the medical realm at the transition from
      late Antiquity to the early Middle Ages.

PMID- 22400190
TI  - [The Bauhaus style in hospitals of Saxony].
AB  - In the first half of 20th century the architecture of hospitals in Germany
      changed considerable. Essential impulses for "The new construct" get out from the
      school of "Bauhaus" in Weimar, Dessau and Berlin. Clear lines and the principle
      of light, air and sun were characteristic of this style. Buildings of such
      hospitals and her creators in Chemnitz, Dresden, Freiberg and Zwenkau, all in
      Saxony, are described and illustrated exemplary.

PMID- 22400191
TI  - [Socialistic university policy between demand and reality--the example of Hans
      Heygster at the Rostock University Hospital of Psychiatry and Neurology].
AB  - The extent and boundaries of political influence are a central issue in the
      history of the German Democratic Republic (GDR). After 1945 socialist leaders
      attempted to exert political influence on education in the Soviet occupied zone
      and the later GDR. The Second University Reform in 1951/52 introduced a
      fundamental break with established university structures. One major aim was the
      establishment of a "new socialist intelligentsia" that was to spread the Marxist
      Leninist theories at universities. Due to a lack of qualified personnel in the
      medical faculties, this aim was far from being reached until the end of the
      1950s. The example of the university lecturer Hans Heygster (1905-1961), who
      worked at the East-German University Hospital of Psychiatry and Neurology in
      Rostock between 1946 and 1953, shows how the GDR rulers sought to influence
      university education. It illustrates the opportunities and restrictions that
      University lecturers in East Germany faced during this time. Heygster soon found
      himself in real conflict, namely between political aims and demands set and
      reality. Based on of archival sources the study elaborates the background, the
      course of events and the consequences of these conflicts.

PMID- 22400192
TI  - [Position hopeless lost--Heinrich Dreuw's lonely struggle against syphilis and
      Salvarsan].
AB  - The invention of Salvarsan (Triaminotrihydroxy-arsenobenzol) in 1910 meant a
      revolution in the medical treatment. Chemotherapy was born and its founder Paul
      Ehrlich is still famous for his experimental work. In medical history mostly
      successes, not widespread discussions about misuse or failing of the new drug
      were. The Berlin doctor Heinrich Dreuw was a key figure in these debates. He and
      his colleagues presented evidence that Salvarsan was not an effective drug and
      just an expensive placebo, which helped pharmaceutical trusts earning more money.
      Dreuw even attacked state medical branches for infringement against patients. At
      last doubts about Salvarsan never disappeared.

PMID- 22400193
TI  - [Was cannibalism practiced in ancient Gaul? Critognatus, the leader of the Celts,
      in the focus of Caesar's propaganda].
AB  - Critognatus, the leader of the Celts, is mentioned only once in the extant
      ancient literature, namely in Caesar's description of the siege of Alesia in BG
      VII 77.2-78.2. Here he is portrayed as a determined patriot who wants to
      encounter the Roman invader bravely and at the risk of all available means.
      Nevertheless, crafty Caesar succeeds in stamping him by propagandistic pinches to
      an evil monster and cannibal. On the one hand Caesar falls back on current Roman
      prejudices towards the Gauls. On the other hand, the endocannibalism practised
      among Celts to a certain extent as a cult action seems to have played a role.
      Caesar's propagandistic methods are transparent and at the same time so effective
      that the label of an ogre sticks to Critognatus until the present day. Caesar's
      portrayal aims above all at the justification of his Gallic War which he wages
      against uncivilized and inhuman opponents who are a menace to Rome and even to
      the culture itself.

PMID- 22400194
TI  - [The admirable effects of panaceas: ideas between antiquity and early modern
      times].
AB  - Panaceas, i. e. medicines that can cure many or almost all diseases, were used
      throughout the history from antiquity until modern times. The paper focuses on
      ideas developed to explain the admirable actions of these medicines. In antiquity
      such actions seem to be related to the large number of ingredients as well as to
      the presence of materials connected to potent poisons (e. g. viper flesh). Later,
      with the advent of alchemy, the alchemical preparation is regarded to produce
      medicines with such properties, the most pregnant example being lapis
      philosophorum. Such explanations are underpinned by the correspondences with
      higher astral influences as espoused by Paracelsus, as well as by van Helmont's
      idea that both disease and cure depend exclusively on the state of the 'spirit of
      life'. At the same time Galenic-like ideas survive, in the sense that panaceas
      are something like universal purifiers. Besides curing diseases panaceas were
      used to ensure long living, permanent health as well as for achieving
      rejuvenation. In this respect, they show an affinity to the so-called 'healing
      power of nature'.

PMID- 22400195
TI  - [Academic medicine in the Soviet Occupation Zone, German Democratic Republic and
      East Germany. Annotated bibliography for the publication period 2001-2010
      including an supplement for the publication period 1990-2000].
AB  - The bibliography lists separate publications of the period 2001-2010 concerning
      the history of academic medicine in the Soviet Occupation Zone and German
      Democratic Republic (GDR) and the transformation of the faculties of medicine
      after 1990. It also complements the previous bibliography (WmM 2001) for the
      publishing period 1990-2000. It registers a total of 153 separate publications
      (monographs, documentations, edited volumes, booklets, catalogues of exhibitions
      and special issues) and grey literature (not bookselling and internet
      publications, unpublished theses).

PMID- 22400196
TI  - [Periodical outbreaks of smallpox presented in two communities in the Westerwald
      in the 18th-century].
AB  - The paper traces 18th-century outbreaks of smallpox in two communities in the
      Westerwald. The distances between the outbreaks are analyzed and comparisons to
      other outbreaks of smallpox are drawn. Furthermore the use of variolation and
      vaccination against smallpox is described.

PMID- 22400197
TI  - [A town-physician in the 18th century: Johann Friedrich Glaser].
AB  - Johann Friedrich Glaser rose from an executioner's family to the position of a
      town physician in Suhl. The contribution concentrates on the importance of this
      position for Glaser. It first looks at the position of town physicians in Suhl.
      They possessed due to certain historical circumstances several duties and rights.
      They enjoyed a remarkably high standing in the town society which made the
      position especially attractive for Glaser as a road to social acceptance. His
      interaction with the medical administration in Dresden (Suhl belonged to the
      jurisdiction of Electoral Saxony) further enhanced his possibilities to interact
      with local and territorial spheres. Altogether, Glaser's official functions
      gained importance over his role as a (medical) scientist, because they offered
      him the best way to gain social and cultural prestige.

PMID- 22400198
TI  - ["Each medical practitioner and ordained physician commissioned by the city of
      Nuremberg shal vow ..." the structures of the public health system in Nuremberg
      at the beginning of the 18th century of Johann Christoph Gotz].
AB  - The medical institutions of Nuremberg were established quite early. The Collegium
      medicum were already founded in 1592. Though this board held responsibility for
      the supervision of pharmacies, the creation of Medizinalordnungen (medical
      legislations) and also had advisory functions, the physicians did not succeed in
      winning a prominent position. The spheres of competence between the different
      groups of medical practitioners were not yet clearly defined. Nevertheless the
      daily work of the practitioner Johann Christoph Gotz (1688-1733) was going
      smoothly due to his cooperation with other doctors, surgeons, midwives and
      pharmacists.

PMID- 22400199
TI  - [Experimental strategies and teleology of the living in diverging contexts-
      physiological research in Xavier Bichat (1771-1802) and Francois Magendie (1783
      1855)].
AB  - At the end of the 18th and the beginning of the 19th century in France, Marie
      Francois-Xavier Bichat and Francois Magendie took quite divergent views on the
      epistemological and methodological importance of physiological investigations in
      the experimental life sciences. For Bichat, morphological physiology represented
      only an auxiliary science for his anatomico-pathological approach to biomedical
      research. Magendie's experimental physiology diverged considerably from Bichat's
      foregoing conception: Although the physiological endeavour had to be seen as
      being essentially based on the localizational work that had afore been performed
      in the field of pathological anatomy, Magendie sensed that the experimental
      approach to physiology represented an important epistemic value in itself. This
      paper traces both the material basis of particular experimental series found in
      Bichat and Magendie as well as the individual laboratory practices which both
      experimental investigators used in their daily research. The focus on the
      epistemological and methodological differences shall be brought in line with that
      of the French experimentalists' divergent explanatory views on the teleological
      and functional phenomena in living organisms as well as the physiological pursuit
      of generating knowledge in the life sciences.

PMID- 22400200
TI  - [The influenza pandemic of 1782, with special reference to its occurrence in the
      Imperial City of Nuremberg].
AB  - In Germany, very little research has been done on the flu pandemic of 1782. The
      year before, in 1781, an epidemic of dysentery had ravaged Central Europe quite
      seriously. The flu pandemic began in Germany in spring 1782. It took its origin
      in the Far East, probably in Imperial China. From there it slowly traveled
      westward and finally hit Russia and Germany. In early 1782, it arrived in eastern
      Prussia. Mortality rose, in Konigsberg (Kaliningrad) mainly people over 30 died.
      From the German coast on the Baltic Sea the virus soon crossed over to England
      and Scotland. Within Germany it slowly moved southward, to places like Berlin,
      Weimar and further south. In Berlin very many people became sick. In spring 1782,
      in many parts of Germany, from east to west, people were bed-ridden. In
      Nuremberg, a young doctor described the symptoms of the disease and the therapy
      he gave to his patients in a pamphlet but apart from that there are few sources.
      Probably not many people consulted a doctor. Mortality in Nuremberg, it seems,
      did not rise very much. The city had been in decline since the 1750s, its
      population now shrunk even further. When this scourge hit Central Europe, the
      Holy Roman Empire was in decline, after an attack of famine and pestilence in the
      early 1770s and that epidemic of dysentery in 1781. It finally collapsed some 25
      years later, in 1806, and the Imperial City of Nuremberg was absorbed by the
      Kingdom of Bavaria.

PMID- 22400201
TI  - [Pharmacy intern of the hospitals of Paris in the 1950's].
AB  - For about two centuries, the hospitals of Paris have had an internship program.
      Every year, 20 to 50 interns were recruited following a difficult competitive
      examination. Their duties covered both the production and the distribution of
      medicines, and biological testing. During the 20th century, biological testing
      meet the exigencies of clinical medicine and it evolved interns participated,
      under the guidance of the hospital pharmacists.

PMID- 22400202
TI  - [Stays in Paris of professors and students from the Faculty of Pharmacy of
      Santiago de Compostela (Spain), 1900-1936].
AB  - In the early twentieth century, if there were an European Capital of biomedical
      research, it was definitely Paris. It was in this city where microbiology was
      born in the 19th century due to the crucial influence of Louis Pasteur. In 1888
      he founded the Pasteur Institute in Paris where the rabies vaccine, that Pasteur
      himself had discovered in 1885, was administrated. This institution was also a
      place to continue his research on infectious diseases and to disseminate its
      findings. It is a private non-profit state-approved foundation that has attracted
      along the years many scientists from France and abroad who have been
      traditionally called "pasteuriens". So it was a world reference centre which has
      produced important scientific discoveries at a rapid pace and where resources
      both material and human, were abundant. The Pasteur institute therefore became
      one of the favourite research facilities of teachers and students from Spanish
      universities during the first third of the twentieth century, thanks to new
      regulations that encouraged training abroad. Scholarship policy promoted by the
      Spanish Government by an organization called Junta para la Ampliacion de Estudios
      e Investigaciones Cientificas (Council for Higher Studies and Scientific Research
      from, 1907 to 1936) formed scientists abroad. The Faculty of Pharmacy of Santiago
      de Compostela sent some of its members to the French capital between 1905 and
      1933. We found that the vast majority chose the Pasteur Institute to conduct the
      studies of biological chemistry and drug synthesis, but always dependent of the
      Faculty of Pharmacy of Paris. Our study focuses on teachers and students who went
      to Paris, the dates, the course of their scientific stay and how these studies
      influenced their later work, once they returned to the Faculty of Pharmacy of
      Santiago de Compostela.

PMID- 22400203
TI  - [Laboratories "Produits Scientia" and mineral waters from Pougues and Carabana].
AB  - In the end of XIXth century, the french "Compagnie des eaux minerales de Pougues
      les-Eaux" begins to exploit the spanish natural purgativ water of Carabana. In
      the same way, Edouard Jeramec, director of the french compagny, decides to
      associate to his firm the best medicine to fight against rickets and
      tuberculosis. He joins the new medical theory wich recommends to give more
      calcium to tubercular patients, called "methode de recalcification du Dr
      Ferrier". Then, with the chemist Emile Perraudin, he creates the pharmaceutical
      laboratory named "Produits Scientia". One of their famous patents medicines will
      be the "Tricalcine".

PMID- 22400204
TI  - [Nicolas Lemery and their sons Louis and Jacques at the Academie royale des
      sciences (2e Part)].
AB  - The first part of our study of the activities of Nicolas Lemery and his sons
      Louis and Jacques at the Academie royale des sciences began with a description of
      the structure of the Academie as a result of its reformation in 1699. Then we
      explained how Nicolas Lemery performed his duties at the Academie beginning from
      1699 until his death in 1715. In this second part we are concentrating in a
      similar way on the activities of Nicolas's son Louis for the Academie, where he
      was a member from 1700 to 1743.

PMID- 22400205
TI  - Blood donation and institutional trust: risk, policy rhetoric, and the men who
      have sex with men lifetime deferral policy in Canada.
AB  - This article examines the process of rebuilding institutional trust in the
      Canadian blood system in the aftermath of the tainted blood scandal. Our focus is
      the policy of lifetime deferral from donating blood for men who have sex with
      men. Drawing on findings from interviews with representatives of Health Canada's
      Expert Advisory Committee on Blood Regulation, the National Liaison Committee,
      Canadian Blood Services, and blood consumer groups, we demonstrate how claims
      making about rights, discrimination, science, and risk contribute to policy
      continuity. We also examine the link between policy continuity and the management
      of reputational risk.

PMID- 22400206
TI  - The graying of "sexual health": a critical research agenda.
AB  - This paper critically interrogates the concept of sexual health as it has evolved
      in relation to older adults. I draw on social and cultural studies of aging,
      feminist studies, and science and technology studies to outline a research agenda
      which treats sexual health as a point of articulation for a range of technologies
      and processes which shape mid- and late-life sexualities. Such an agenda may be
      able to more fully interrogate the sites and processes by which sexualities are
      being shaped, the forms of sexual agency on offer to older people, and the
      contemporary reconstruction of sexual life courses.

PMID- 22400207
TI  - A review on melt-state viscoelastic properties of polymer nanocomposites.
AB  - The mixing of polymer matrices with nanoparticles to form composite materials has
      been an area of great research interest. The mechanical and rheological
      properties of such composite materials are directly related to the properties of
      the matrix polymer, the properties of the nano-filler, the strength and nature of
      the interfacial interactions between the polymer matrix and the filler, and
      finally, the surface area of the interfacial bonds. In the case of nano-filled
      composite materials, the area of interfacial bond is determined by the aspect
      ratio of the dispersed particles and the loading level. As the nanoparticles are
      more nicely dispersed in the polymer matrix, the thickness of the dispersed
      particles decreases, and as a result the aspect ratio and the affect of the
      filler on the matrix mechanical and other properties increases. One such
      nanoparticle is clay or layered silicate. Understanding the rheological
      properties of polymer layered silicate nanocomposites (PLSNs) under molten state
      is crucial to gain fundamental knowledge for the processability and the structure
      property relationship of these materials. In the case of PLSNs, the melt
      rheological behaviors are strongly influenced by their nanostructure. In this
      article, we aim to critically review, from the available literatures, the recent
      progress in the melt-state rheological properties of various types of PLSNs and
      the relationship with structure. Both the linear and non-linear rheological
      properties have been reviewed with a particular focus on the effect of applied
      shear, both steady and dynamic, on the orientation of silicate platelets inside
      the polymer melts. To begin this, a brief description of the structure and
      properties of layered silicates have been summarized.

PMID- 22400208
TI  - Atomic force spectroscopy evidence of non-specific adhesion of Aggregatibacter
      actinomycetemcomitans.
AB  - Aggregatibacter actinomycetemcomitans is a gram-negative periodontopathogen found
      within the subgingival plaque on the tooth surface. It is associated with
      localized aggressive periodontitis, a severe form of periodontitis in
      adolescents, and is the cause various extra-oral infections. The ability of this
      organism to tenaciously adhere to abiotic surfaces has been attributed to bundle
      forming type IVb-like fimbriae whose major component is the fimbrial lower
      molecular weight protein (Flp). In this study the adhesion of purified Flp
      fimbriae isolated from A. actinomycetemcomitans to materials with different
      surface chemistries was measured using atomic force microscopy (AFM). The
      adhesion of Flp fimbriae to uncoated and saliva-coated tooth, hydroxylapatite,
      and glass surfaces was compared. Force data were used to quantify the magnitude
      of adhesion of the fimbriae and force-distance profiles were used to predict the
      mechanisms of adhesion. The results of this study confirm that non-specific
      interactions likely dominate the adhesion of these fimbriae to the surfaces used
      in this study. However, force data indicate that non-specific electrostatic
      interactions may be more significant under the conditions used in this study.
      Salivary coatings did affect both the hydrophobicity and adhesion of these
      fimbriae to the surfaces used in this study. Additionally, these data demonstrate
      the affect of salivary proteins on bacterial adhesion in the oral cavity.

PMID- 22400209
TI  - Molecular dynamics simulations of end-tethered single-stranded DNA probes on a
      silica surface.
AB  - The structure of DNA molecules tethered to surfaces may significantly affect the
      efficiency of hybridization on the DNA microarray. Understanding the structure of
      single-stranded DNA (ssDNA) tethered to surfaces is critical for applying the
      molecular recognition function of DNA microarrays. Although a number of
      experimental methods have been applied to determine the structure of the DNA
      probe on surfaces, they can not provide enough information on the dynamical
      behavior of the ssDNAs on surfaces. Herein, we investigated the dynamics and
      interaction of seven DNA probes tethered on a silica surface by a molecular
      dynamics simulation. From the simulation results, we examined the structure and
      dynamics of the ssDNAs, by calculating the root-mean-square derivations, the tilt
      angles, the radius of gyration, and the distances of the neighboring ssDNAs. The
      data obtained from our simulation suggests the packing density has a significant
      effect on the overall structure and molecular orientation change of surface
      tethered ssDNAs, which is complementary to the recent experimental reports. Our
      simulation provided a structural insight, which is helpful to better understand
      the behavior of ssDNA on surfaces and optimize the design of DNA microarray.

PMID- 22400210
TI  - Synthesis of biomimetic poly[2-(methacryloyloxy)ethyl phosphorycholine]-coated
      magnetite nanoparticles via surface-initiated atom transfer radical
      polymerization.
AB  - Modification of magnetite nanoparticles with biomimetic poly[2
      (methacryloyloxy)ethyl phosphorycholine] (poly(MPC)) via surface-initiated atom
      transfer radical polymerization (ATRP) was carried out. Fourier transform
      infrared (FT-IR) spectroscopy, thermogravimetric analyses (TGA) and zeta
      potential studies indicated that well defined poly (MPC) was successfully grafted
      on the surface of magnetite nanoparticles. X-ray diffraction results showed the
      structure of magnetite nanoparticles after surface modification was not changed.
      The poly (MPC)-coated magnetite nanoparticles had a mean transmission electron
      microscopy (TEM) diameter of 11 +/- 1.5 nm. The resulting nanomaterials were
      superparamagnetic at room temperature, exhibited good colloidal stability in
      aqueous media and good responsibility to magnetic field. Such magnetite
      nanoparticles with biomimetic surface have potential application in prolonging
      circulation time in vivo.

PMID- 22400211
TI  - Preparation of photocrosslinkable polystyrene methylene cinnamate nanofibers via
      electrospinning.
AB  - Nanoscaled photocrosslinkable polystyrene methylene cinnamate (PSMC) nanofibers
      were fabricated by electrospinning. The PSMC was prepared by the modification of
      polystyrene as a starting material via a two-step reaction process,
      chloromethylation and esterification. The chemical structure of PSMC was
      confirmed by 1H NMR and Fourier transform infrared spectroscopy (FT-IR). The
      photosensitivity of the PSMC was investigated using ultraviolet (UV)
      spectroscopic methods. Electrospun PSMC nanofiber mat showed excellent solubility
      in many organic solvents. UV irradiation of the electrospun mats led to
      photodimerization to resist dissolving in organic solvents. The morphology of the
      nanofiber was observed by scanning electron microscopy (SEM) and the result
      indicated that the average diameter of nanofibers is 350 nm and the crosslinked
      nanofibers were not collapsed after dipping into organic solvent showing good
      solvent-stability. This photocrosslinked nanofibers has the potential application
      in filtration, catalyst carrier and protective coating.

PMID- 22400212
TI  - Hydrothermally stable periodic mesoporous ethane-silica and bimodal mesoporous
      nanostructures.
AB  - We report the hydrothermally stable organized periodic mesoporous organosilicas
      (PMOs) and bimodal mesoporous structures by using mixed templates of oligomeric
      alkyl-ethylene oxide and ionic surfactants under basic conditions. Oligomeric
      alkyl-ethylene oxide surfactant [(Polyoxyethylene (2) cetyl ether, structure is
      C16H33(OCH2CH2)nOH, n-2, hereafter known as B52) and ionic surfactant
      (cethyltrimethylammonium bromide (CTAB)) templating systems form mixed micelles
      that self-assemble into well-ordered hexagonal and bimodal mesostructures. The X
      ray diffraction (XRD), transmission electron microscopy (TEM), BET, NMR and
      hydrothermal study have been used to investigate the effects of B52 on the
      formation of various PMOs. It is found that surface structural properties of
      mesostructures largely depend on the concentration of the B52 in the surfactant
      solution. The addition of B52 in the surfactant solution is not only improves
      mesostructural ordering and also enables to produces mesostructures with tuned
      surface structural properties. The final PMO structure shows good hydrothermal
      stability and can withstand for 72 h in boiling water, due to the hydrophobic
      pore wall chemistry in ethane-bridged PMO framework (triple bond Si-CH2-CH2-Si
      triple bond) and relatively more condensed framework such T3 supported by NMR
      spectrum. So, the lacking affinity for water through the favorable hydrophobic
      framework chemistry enhances the hydrothermal stability.

PMID- 22400213
TI  - Microstructure of the native oxide layer on Ni and Cr-doped Ni nanoparticles.
AB  - Most metallic nanoparticles exposed to air at room temperature will be
      instantaneously oxidized and covered by an oxide layer. In most cases the true
      structural nature of the oxide layer formed at this stage is hard to determine.
      As shown previously for Fe and other nanoparticles, the nature of the oxides form
      on the particles can vary with particle size and nature of the oxidation process.
      In this paper, we report the morphology and structural features of the native
      oxide layer on pure Ni and Cr-doped Ni nanoparticles synthesized using a cluster
      deposition process. Structural characterization carried out at the atomic level
      using aberration corrected high resolution transmission electron microscopy
      (HRTEM) in combination with electron and X-ray diffractions reveals that both
      pure Ni and Cr-doped Ni particles exposed to air at room temperature similarly
      possesses a core-shell structure of metal core covered by an oxide layer of
      typically 1.6 nm in thickness. There exists a critical size of approximately 6
      nm, below which the particle is fully oxidized. The oxide particle corresponds to
      the rock-salt structured NiO and is faceted on the (001) planes. XPS of O-1s
      shows a strong peak that is attributed to (OH)-, which in combination with the
      atomic level HRTEM imaging indicates that the very top layer of the oxide is
      hydrolyzed.

PMID- 22400214
TI  - Growth kinetic and characterization of Mg(x)Zn1-xO nanoneedles synthesized by
      thermal oxidation.
AB  - Mg(x)Zn1-xO nanoneedles were synthesized on alumina substrate by using thermal
      oxidation technique under normal atmosphere. Zn powder and MgO powder were mixed
      and heated to form Mg(x)Zn1-xO with x content of 0-0.3 by mol at heating
      temperature and time of 400-1000 degrees C and 24 h. The morphology of Mg(x)Zn1
      xO nanoneedle was characterized by filed emission scanning electron microscope
      (FE-SEM). It was found that the needle-like nanostructures with the sharp ends
      were observed outward from microparticles at 400-800 degrees C. From EDS, XRD,
      and TEM analysis, it was suggested that Mg(x)Zn1-xO alloy was formed with no
      segregation of MgO in Mg(x)Zn1-xO alloy after thermal oxidation process. Also,
      from reflectance spectra, the Mg(x)Zn1-xO nanoneedle exhibited higher energy gap
      than that of ZnO films for entire Mg content indicating widening band gap energy
      due to alloying effect. Moreover, we have proposed the growth mechanism of
      Mg(x)Zn1-xO nanoneedles based on growth kinetic of nucleation formation. This
      growth model can be explored to explain nanostructure of other metal-oxide alloy
      prepared by thermal oxidation.

PMID- 22400215
TI  - One-step synthesis and flame retardancy of sheaf-like microcrystal antimony
      oxychloride.
AB  - A mild and facile solution route has been developed for large-scale synthesis of
      sheaf-like antimony oxychloride Sb8O11CI2 (H2O)6 microcrystal at room
      temperature. The morphologies and structures of the as-prepared products were
      characterized by X-ray powder diffraction (XRD), scanning electron microscopy
      (SEM), and transmission electron microscopy (TEM). A mechanism for the formation
      of the sheaf-like microstructure was tentatively proposed. The shape regulation
      was attributed to the capping mode of the PVP-directed antimony oxychloride
      crystal. The thermogravimetric and differential thermal analysis (TG/DTA) were
      employed to investigate thermal decomposition mechanism and temperature-dependent
      phase transition of antimony oxychloride Sb8O11CI2 (H2O)6 in the air. The
      flammable property determined by the cone calorimeter showed excellent flame
      retardancy when applied this antimony oxychloride in poly (vinyl chloride) (PVC)
      polymer.

PMID- 22400216
TI  - Vibration and orientation of diatomic molecules flowing through small carbon
      nanotubes.
AB  - With their unique long cylindrical shape, carbon nanotubes may one-day form
      nozzles for nano-scale printing or flow into a chamber. Since the scale of the
      flowing molecules is similar to the diameter of the nanotubes, molecular
      vibration, orientation and density become influenced by the confinement during
      flow. We have studied the flow of diatomic molecules through carbon nanotube
      nozzles using non-equilibrium molecular dynamics simulations, in an effort to
      gain a greater understanding about the fundamental properties of such molecules
      in such a setting. The frequency of vibration of the molecules is shown to be
      dependent on the density inside the nanotubes and follow the same relation as an
      experimental micro-scale density-frequency study suggests, although only for
      nanotubes above a certain diameter. Meanwhile no relation is found between the
      frequency of vibration and the flow rate. The effect of nanotube diameter on the
      orientation of the molecules is also examined in detail, showing the transition
      between axial and radial orientation, with "pull" and "push" effects determining
      the orientation.

PMID- 22400217
TI  - Hydrothermal synthesis of cdS nanoparticle-decorated TiO2 nanobelts for solar
      cell.
AB  - We fabricated a solar cell using a hybrid film consisting of CdS nanoparticle
      decorated TiO2 nanobelts, which were synthesized via a modified alkaline
      hydrothermal method. The hybrid film is flexible and contains homogeneous CdS
      nanoparticle light absorbers. Furthermore, the type II heterostructure of
      CdS/TiO2 facilitates charge separation in the CdS nanoparticle-decorated TiO2
      nanobelts. The solar cell demonstrated a light-electricity power conversion
      efficiency of 2.52%. Next, we deposited the CdS nanoparticle-decorated TiO2
      nanobelts onto a ZnO nanowire array forming an antireflective hybrid structure.
      The power conversion efficiency of the cell with the hybrid photoanode reached
      2.84%.

PMID- 22400218
TI  - Valley blockade quantum switching in Silicon nanostructures.
AB  - In analogy to the Coulomb and the Pauli spin blockade, based on the electrostatic
      repulsion and the Pauli exclusion principle respectively, the concept of valley
      blockade in Silicon nanostructures is explored. The valley parity operator is
      defined. Valley blockade is determined by the parity conservation of valley
      composition eigenvectors in quantum transport. A Silicon quantum changeover
      switch based on a triple of donor quantum dots capable to separate electrons
      having opposite valley parity by virtue of the valley parity conservation is
      proposed. The quantum changeover switch represents a novel kind of hybrid quantum
      based classical logic device.

PMID- 22400219
TI  - MgZnO nanowires based deep ultraviolet heterojunction light emitting diodes.
AB  - Vertically aligned Mg alloyed ZnO nanowires were successfully grown by Chemical
      Vapor deposition method in a tube furnace. Structural analysis found that the
      MgZnO nanowires are with single crystalline without phase separations. The atomic
      ratio of Mg/O in the nanowire was determined to be approximately 15%.
      Photoluminescence spectra show that the band gap of ZnO nanowire was tuned to
      approximately 3.6 eV due to Mg incorporation. N-type MgZnO nanowires/p-type GaN
      was used for heterojunctional light emitting diode fabrication.
      Electroluminescence measurement yielded ultraviolet emission peaks, which
      includes a deep ultraviolet at approximately 340 nm. The results suggest that
      successful Mg alloying in ZnO nanowires was achieved and is promising for deep
      ultraviolet devices.

PMID- 22400220
TI  - Evaluation of the sulfo-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1
      carboxylate coupling chemistry for attachment of oligonucleotides to magnetic
      nanobeads.
AB  - The sulfo-SMCC (Succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate)
      coupling chemistry was evaluated for immobilization of oligonucleotides onto 130
      nm sized magnetic nanobeads aimed for bio-detection in a magnetic readout assay.
      The chemistry was found to produce a high surface coverage of approximately 93 +/
      10 oligonucleotides per bead whereas stability tests showed that about 50% of
      the oligonucleotides detached from the bead surfaces after eight weeks of storage
      in a buffer solution. It was shown that bead aggregation prior to magnetic
      readout could be suppressed by incubating the samples at 70 degrees C for 30 min.
      The same temperature was also shown to be the most favorable for hybridization
      between the oligonucleotide functionalized beads and rolling circle amplified DNA
      molecules. This should simplify the heating procedure in a biosensor in which
      hybridization and magnetic readout is performed in the same compartment.

PMID- 22400221
TI  - Resistive switching in copper oxide nanorods: a bottom up approach applicable for
      enhanced scalability.
AB  - Reversible, stable and reproducible resistive switching in a parallel network of
      Cu2O nanorods, observed in the present study, highlights the advantages of using
      nanorods in comparison to normally used thin films. Unipolar and symmetric
      current-voltage characteristics of the metal/insulator/metal structure consisting
      of Hg top contact/Copper oxide (Cu2O) nanorods/Ag bottom contact in a sandwich
      configuration shows electroforming at about 11 V, reproducible reset and set
      points at 0.53 +/- 0.03 and 4.2 +/- 0.02 V and a high OFF/ON resistance ratio >
      10(3). Slope of current-voltage characteristics and current contrast in CAFM
      mapping indicate that filamentary conduction mechanism is responsible for
      resistive switching. This study sets the foundation for fabricating a nanorods
      based resistive random access memory device and thus a manifold increase in the
      device scalability.

PMID- 22400222
TI  - Water-soluble polythiophene-single walled carbon Nanotube bulk heterojunction.
AB  - Two symmetrical terminal electrodes made of indium tin oxide (ITO) were employed
      to study the current-voltage characteristics of a bulk-heterojunction consisting
      of water soluble polythiophene and single walled carbon nanotubes (SWCNT).
      However, the current-voltage curves were asymmetrical, attributed to the
      polarization induced by the initial bias voltage. The polymer-SWCNT
      heterojunction were superior to the pristine polymer in both dark conductivity
      and photoconductivity by two orders of magnitude. Additionally, the open-cell
      voltage of 0.075 V was observed from the heterojunction even though the
      electrodes were symmetrical. The high conductivity and photoresponse originated
      from the high conductivity, high interconnectivity and hole doping capability of
      CNT.

PMID- 22400224
TI  - Morphology modification of silver microstructures fabricated by multiphoton
      photoreduction.
AB  - We have investigated the morphology modification of silver microstructures
      fabricated by the multiphoton photoreduction process. The microstructures have
      been fabricated by a femtosecond laser under different irradiation time and
      repeated scanning numbers. Trans-4-[4-(dimethylamino)-N-methylstilbazolium] p
      tosylate (DAST) was used as photosensitizer and effectively reduced the laser
      power to 0.66 mW. The increase of the irradiation time and repeated scanning
      induced more reduction in the multiphoton photoreduction microfabrication
      process, resulting in the optimization of the linewidth. The fusion of silver
      nanoparticles was confirmed, which led to the morphology change of silver
      microstructures for achieving the compact metallic microstructures. The result
      would provide an important protocol to fabricate the metallic microstructures for
      the electronic and photonic applications.

PMID- 22400223
TI  - Preparation of a cationic nanoemulsome for intratumoral drug delivery and its
      enhancing effect on cellular uptake in vitro.
AB  - To develop an appropriate carrier for intratumoral drug delivery,
      cetyltrimethylammonium bromide (CTAB) modified nanoemulsome (CTAB-NES) was
      designed and prepared by solvent evaporation method. Coumarin-6 was chosen as the
      fluorescent probe and the conventional nanoemulsome (NES) without CTAB
      modification served as a control. The results demonstrated that CTAB-NES had a
      smaller particle size of 71.9 +/- 4.32 nm, considerate positive zeta potential of
      +48.7 +/- 0.2 mV, preferably entrapment efficiency of 97.483 +/- 0.693% and the
      release of coumarin-6 in 24 h was little. The in vitro cytotoxicity of CTAB-NES
      to the CHO cells and MCF-7 cells increased consistently with concentrations and
      was higher than that of NES, especially to the cancer cells. Both the
      fluorescence microscopy images and HPLC assay verified that the cellular uptake
      of CTAB-NES in MCF-7 cells was much higher than that of NES, and the uptake was
      time-, concentration- and temperature- dependent. The uptake mechanism results
      demonstrated that the internalization of CTAB-NES and NES involved clathrin- and
      caveolae-mediated endocytosis while macropinocytosis only influenced the uptake
      of CTAB-NES in MCF-7 cells for CTAB could mediate adsorptive pinocytosis. Thus,
      CTAB-NES with high positive charge and good intracellular uptake ability could be
      a promising drug carrier for intratumoral drug delivery.

PMID- 22400225
TI  - The Faraday rotation angle of Ni nanowire arrays: its dependence on photon energy
      and nanowire size.
AB  - The magneto-optical properties of Ni nanowire arrays embedded in anodic aluminum
      oxide templates are studied, for a selection of photon energies, as a function of
      their diameter and length for the first time. This was achieved by the
      determination of Stokes parameters of the transmitted light. The magneto-optical
      response is found to differ considerably from that of the bulk material. At all
      photon energies studied, a linear association of the Faraday rotation angle with
      nanowire length has been observed; moreover, a proportional relationship between
      rotation angle per unit length and nanowire diameter has also been also observed,
      consistent with our earlier work on Fe and Co nanowires. The relationship between
      the Faraday rotation angle per unit length with different nanowire diameters and
      photon energy has been found to exhibit clear spectroscopic structure.

PMID- 22400226
TI  - Dual gas-bubble-assisted solvothermal synthesis of magnetite with tunable size
      and structure.
AB  - We present a facile solvothermal approach by employing ammonium bicarbonate
      (NH4HCO3) and ammonium acetate (NH4Ac) as dual gas-bubble-generating structure
      directing agent to produce of magnetite (Fe3O4) particles with tunable size
      ranging from 90 nm to 400 nm and controllable structures including porous and
      hollow construction. The size, morphology and structure of the final products are
      achieved by simple adjustment of the molar ratio of NH4HCO3 and NH4Ac, ammonium
      ion concentration and the reaction time. The results reveal that the molar ratio
      of NH4HCO3 and NH4Ac strongly influenced the morphology and size of magnetite
      particles, even could decide the kind of architecture including solid, hollow and
      porous to form. Particularly, ammonium ion molar concentration plays a
      significant role in controlling size and magnetic property for magnetite
      particles. Simultaneously, prolonging the reaction time is beneficial to the
      magnetite particles growth and inner space escalation with altered reaction time
      at a certain concentration of ammonium and molar ratio of NH4HCO3 and NH4Ac. Such
      a design conception of dual gas-bubble-assistance used here is promisingly
      positive and significant for hollow magnetic particles fabrication and may be
      extended to other nano-scale hollow construction.

PMID- 22400227
TI  - Preparation of tetrapod-like nanostructure array and used as the surface-enhanced
      Raman scattering substrates.
AB  - Nanostructure surface composed of tetrapod-like structure with the period of
      about 2 microm has been made by simple nanoprinted method, the collodion was
      poured directly on the surface of the template and tore off after it became
      solidification, and then a layer of gold was sputtered on the collodion surface.
      The electric field distributions of the tetrapod-like structure with different
      size and period have been simulated using finite element method. Surface-enhanced
      Raman spectra mapping image gotten from the substrates illustrated the uniform
      enhancement property of it. The diluted aqueous solution of Rhodamine 6G (50 nM)
      was used to test the enhanced property of substrates for trace detection and good
      quality spectra has been gotten. The spectra of melamine with the concentration
      of 1 mg/L (7.9 microM) on the substrates were gotten to show the enhanced ability
      for molecule with small Raman scattering cross section.

PMID- 22400228
TI  - Pt, Rh and Pt-Rh nanoparticles on modified single-walled carbon nanotubes for
      hydrogenation of benzene at room temperature.
AB  - Nanometer-sized Pt, Rh, and bimetallic Pt-Rh particles can be deposited on
      surface of phenylacetic acid functionalized single-walled carbon nanotubes
      (SWCNTs) by a microemulsion method. The SWCNT-supported metallic nanoparticles
      show much greater catalytic activities compared with commercially available
      carbon-supported Pt and Rh catalysts for hydrogenation of neat benzene under mild
      experimental conditions. The bimetallic Pt-Rh nanoparticle catalyst synthesized
      by this method shows an enhanced activity relative to individual SWCNT-supported
      Pt and Rh nanoparticle catalysts. The SWCNT-supported metal nanoparticle
      catalysts can be recycled and reused at least five times without losing their
      activity. The hydrogenation reactions performed under our experimental conditions
      would not affect the pi-pi stacking holding phenylacetic acid on SWCNT surface.

PMID- 22400229
TI  - Simple facile route for the preparation of graphite oxide and graphene.
AB  - A simple method is reported for the preparation of graphite oxide (GO) and
      graphene using KCIO3/NaNO3/H2SO4 and Na2S as oxidizing agent as oxidizing and
      reducing agents respectively. The formation of GO and graphene have also been
      confirmed by X-ray diffraction studies, UV-visible, spectroscopy, FTIR and Raman
      spectroscopy. The morphology, surface charge characteristic and thermal stability
      behaviour have been studied by SEM/TEM, Zeta potential measurements,
      thermogravimetric analysis.

PMID- 22400230
TI  - One pot synthesis and characterization of ultra fine CeO2 and Cu/CeO2
      nanoparticles. Application for low temperature CO oxidation.
AB  - Ultra fine cerium oxide and copper doped cerium oxide nanoparticles are prepared
      in a one-step reaction by thermal decomposition of Ce acetate in commercial
      oleylamine. The products are highly crystalline and were characterized by XRD,
      Raman spectroscopy, XPS, TEM and BET. The TEM images show that the CeO2 particles
      prepared are uniformly nanosized. The size of the nanoparticles can be controlled
      in the sub-10 nm range by the presence of other capping agent in the reaction
      mixture such as tri-octylphosphine oxide and oleic acid. The copper doped cerium
      oxide nanoparticles show high specific surface area (up to 299 m2/gr) and high
      catalytic activity for the low temperature CO oxidation even at low copper
      loading such as 9 at.%.

PMID- 22400231
TI  - Formation of Janus TiO2 nanoparticles by a pickering emulsion approach applying
      phosphonate coupling agents.
AB  - Anisotropic surface modification of TiO2 nanoparticles was achieved applying a
      Pickering emulsion approach. TiO2 nanoparticles were prepared by sol-gel routes
      which allowed an excellent control over their size and morphology. The obtained
      colloids were further used as stabilizers in the formation of oil-in-water
      Pickering emulsion. For reasons of comparison, also commercially available
      titanium dioxide nanoparticles (Evonik AEROXIDE TiO2 P25) were used in the
      functionalization experiments. An organophosphorus coupling agent present in the
      oil phase coordinated to the surface of the anatase nanoparticles. In such a way
      an anisotropic surface modification of the particles was achieved which increased
      the stability of the Pickering emulsion. Spectroscopic studies revealed the
      presence of organophosphorus coupling agents which exhibited a covalent bonding
      to the surface of the particles. Thermogravimetric analyses confirmed a lower
      surface coverage of the particles modified in emulsion compared to those modified
      in suspension. Reactions of organophosphorus coupling agents containing an
      additional methacrylate group applying an organic monomer (methyl methacrylate)
      as the oil phase of the Pickering emulsion resulted in hybrid TiO2@polymer
      spheres. Spectroscopic characterization of the resulting particles revealed that
      the phosphonates were coordinated to the TiO2 surface and at the same time
      copolymerized with the MMA within the oil droplet. Morphological investigations
      of the isolated final product showed that the material was composed of polymer
      spheres with the stabilizing TiO2 nanoparticles on their surface.

PMID- 22400232
TI  - Effects of the host morphologies on luminescence properties of Nd(3+)-doped LaF3
      nanoparticles.
AB  - By using different surfactants, several host morphologies including rod-like, pot
      like and shuttle-like of LaF3:Nd3+(1% mol) nanoparticles were prepared by a
      simple microemulsion hydrothermal method, and their properties were characterised
      by XRD, TEM and photoluminescence spectroscopy. The experimental results
      indicated that the rod-like and pot-like nanocrystals possess well shaped hollow
      structures. The analysis of spectra proved that the local environment around the
      dopant ion changed with the different host morphology, which in turn influenced
      the luminescence properties. The luminescence lifetimes derived from
      biexponential fitting were 615 micros (nanopots), 419 micros (nanorods) and 194
      micros (nanoshuttles), respectively. This phenomenon is ascribed to the weakening
      effect of hollow or fenestral structures to the nonradiative ratio.

PMID- 22400233
TI  - Properties of polycarbonate (PC)/multi-wall carbon nanotube (MWCNT)
      nanocomposites prepared by melt blending.
AB  - This investigation deals with an easy method to develop electrical conductivity
      in polycarbonate (PC)/multi-wall carbon nanotube (MWCNT) nanocomposites with low
      loading of MWCNT. This was achieved by melt-blending of in-situ bulk polymerized
      low molecular weight poly(methyl methacrylate) (PMMA)/MWCNT nanocomposites and PC
      in various compositions at 280 degrees C in internal mixer. Differential scanning
      calorimetry (DSC) study showed single Tg in (85/15 w/w) PC/PMMA blend, indicating
      miscibility of PC and PMMA in the blend. Scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM) studies of the melt-blended PC/PMMA/MWCNT
      nanocomposites revealed homogeneous dispersion and distribution of MWCNTs in PC
      matrix. Finally, through optimizing the blending composition of PC and PMMA/MWCNT
      nanocomposites, electrical conductivity of 3.74 x 10(-7) S x cm(-1) was achieved
      in the (85/15 w/w) PC/PMMA/MWCNT nanocomposites with the MWCNTs loading as low as
      approximately 0.37 wt%. Storage modulus of PC was found to increase significantly
      in presence of small amount (0.37 wt%) of MWCNTs in the nanocomposites.

PMID- 22400234
TI  - Metformin hydrochloride-loaded poly(vinyl alcohol) composites as drug delivery
      systems.
AB  - A straightforward method is proposed for the preparation of drug-loaded
      biocompatible polymer composites based on the freeze drying technique. The
      solution of poly(vinyl alcohol) (PVA) and metformin hydrochloride (MH) is frozen
      using liquid nitrogen and the ice crystals are removed by sublimation through
      freeze drying, which results in the formation of MH-loaded PVA composite. By
      controlling the PVA concentration in the solution, both MH-loaded PVA fibers and
      porous products can be obtained. The synthesized MH-loaded PVA composites are
      characterized with scanning electron microscopy (SEM), powder X-ray diffraction
      (XRD), Fourier-transformed infrared spectroscopy (FTIR) and differential scanning
      calorimetry (DSC). The drug release behavior of the as-prepared products is
      studied to reveal their potential use in drug delivery system.

PMID- 22400235
TI  - Charge dependent catalytic activity of gasborne nanoparticles.
AB  - It is shown experimentally that the electric charge of unsupported catalyst
      particles has a major influence on the methanation of CO with nano-sized Ni
      particles as catalyst at temperatures between 680 K and 720 K. Neutral particles
      showed an apparent activation energy of 148 kJ/mol, significantly higher than the
      apparent activation energies of 43 kJ/mol and 60 kJ/mol for negatively and
      positively charged particles, respectively. The obtained activation energies are
      comparable to energies obtained for different sites on alumina supported nickel
      catalysts. The change in activation energy can be qualitatively explained by
      different electron interchange between the chemisorbed species and the catalyst.
      We suggest that the observed effect of electron enhancement or depletion on
      catalysis is also a governing effect in strong metal support interaction (SMSI),
      where the displacement of electrons is related to the contact potential between
      catalyst and substrate.

PMID- 22400236
TI  - Challenges and future expectations of reversed gene therapy.
AB  - Gene therapy is a genetic intervention used for the prevention or treatment of
      diseases by targeting selected genes with specific nucleotides. The most common
      form of gene therapy involves the establishment of a function by transfer of
      functional genes or correction of mutated genes. In other situations, suppression
      or abolishment of a function is required in order to balance a complicated
      regulatory system or to deplete cellular molecules crucial for pathogen
      infection. The latter in fact employs an opposite strategy compared to those used
      in classical gene therapy, and can be defined as reversed gene therapy. This
      paper takes CCR5-based stem cell gene therapy as an example to discuss the
      challenges and future expectations of reversed gene therapy.

PMID- 22400237
TI  - Influence of the physical, structural and chemical properties on the
      photoresponse property of magnetron sputtered TiO2 for the application of water
      splitting.
AB  - The production of hydrogen from water (called "water splitting"), utilises
      sunlight as an energy source (solar-hydrogen) in a photoelectrochemical (PEC)
      solar cell, is a promising source of green energy. In this work, a PEC was used,
      for evaluating the photoactivity of a thin film TiO2 based photoanode by
      measuring photocurrent (which is comparable to hydrogen production rate by water
      splitting process in PEC). The main focus of this work is to study the effect of
      the TiO2 nanosurface and bulk properties on the photoresponse properties of the
      photoanode. The TiO2 coatings (360-400 nm) were deposited using a closed field
      reactive magnetron sputtering system. The structure and morphology of the TiO2
      coatings were systematically altered by varying the deposition pressure between 5
      x 10(-4) to 1 x 10(-2) mbar. The properties of the deposited nano-coatings were
      determined using Ellipsometry, SEM, AFM, profilometry, XPS, Raman and X-ray
      diffraction (XRD). Coating properties were correlated with the light absorption
      and photocurrent performance which were evaluated using UV-Vis spectroscopy and
      tri-electrode potentiostat measurements respectively. It was concluded from this
      study that the coating deposition pressure has a pronounced effect on the TiO2
      photoanode properties leading to a significant enhancement in the photoactivity
      in PEC cell. Over a six fold increase in photocurrent at applied potential 0 V
      was observed for TiO2 photoanode prepared at 4 x 10(-3) mbar as compared to 5 x
      10(-4) mbar. A correlation has been established between the deposition pressure,
      nano surface morphology and bulk properties, UV-Vis light absorbance and bandgap
      value, and the consequently higher (i) photocurrent density, (ii) negative flat
      band, and (iii) open circuit potential measured in Photoelectrochemical (PEC)
      cell.

PMID- 22400238
TI  - Study on micro-structure and morphological evolution of Fe/Pt nano-magnetic film.
AB  - One of the vertical magnetic recordings medium materials of the hard disk drive
      (HDD) is a Fe/Pt thin film. The development of ultra-high density magnetic
      recording medium in next generation is expected the magnetic disks such as HDD
      with capacity enlargement of the data. In order to study effectiveness of the
      proposed sputtering method, we evaluated micro structure, magnetic and the
      mechanical properties of a Fe/Pt thin film by some sputtering process conditions.
      From research results, effect sputtering conditions on micro-structure and
      mechanical properties of Fe/Pt nano film are verified.

PMID- 22400239
TI  - Detection of change in fluorescence between reactive cyan and the yellow
      fluorophores using a-SiC:H multilayer transducers.
AB  - Optical colour sensors based on multilayered a-SiC:H heterostructures can act as
      voltage controlled optical filters in the visible range. In this article we
      investigate the application of these structures for Fluorescence Resonance Energy
      Transfer (FRET) detection, The characteristics of a-SiC:H multilayered structure
      are studied both theoretically and experimentally in several wavelengths
      corresponding to different fluorophores. The tunable optical p-i'(a-SiC:H)-n/p
      i(a-Si:H)-n heterostructures were produced by PECVD and tested for a proper fine
      tuning in the violet, cyan and yellow wavelengths. The devices were characterized
      through transmittance and spectral response measurements, under different
      electrical bias and frequencies. Violet, cyan and yellow signals were applied in
      simultaneous and results have shown that they can be recovered under suitable
      applied bias. A theoretical analysis supported by numerical simulation is
      presented.

PMID- 22400240
TI  - Ultraviolet curing for surface modification of textile fabrics.
AB  - In this study, cotton, polyester and polyamide fabrics were treated by radical or
      cationic ultraviolet curing of different commercial products conferring water and
      oil repellency. Moreover, radical ultraviolet curing of chitosan was applied to
      confer antimicrobial properties. The advantages of this technology are well known
      making it very interesting for industrial applications: energy savings, low
      environmental impact, simple, cheap and small equipment, high treatment speed.
      The polymerization was controlled through weight gain and gel content
      measurements, while the properties of hydro and oil repellency were determined in
      terms of contact angle, moisture adsorption and water vapor permeability. The
      polymer distribution on fabric surfaces was investigated by scanning electron
      microscopy and atomic force microscopy. However the fabrics treated with chitosan
      were subjected to the standard test for determining the antimicrobial activity.
      Finally the finished cotton samples were subjected to washing fastness tests.

PMID- 22400241
TI  - CaCu3Ti4O12 nanoparticles using polyvinyl pyrrolidone: synthesis and dielectric
      properties.
AB  - Nanocrystalline CaCu3Ti4O12 powders with particle sizes of 39.28 8.12 nm were
      synthesized by a simple modify sol-gel using PVP (Poly-vinyl-pyrrolidone). The
      synthesized precursor was characterized by TG-DTA to determine the thermal
      decomposition and crystallization temperature which was found to be at above 500
      degrees C. The precursor was calcined at 800 degrees C in air for 8 h to obtain
      nanocrystalline powders of CaCu3Ti4O12. The calcined CaCu3Ti4O12 powders were
      characterized by XRD, FTIR, SEM and TEM. Sintering of the powders was conducted
      in air at 1100 degrees C for 16 h. The XRD results indicated that all sintered
      samples have a typical perovskite CaCu3Ti4O12 structure and a small amount of
      CaTiO3. SEM micrographs showed the average grain sizes of 1.86 +/- 0.69 /m for
      the sintered CaCu3Ti4O12 ceramic prepared using the CaCu3Ti4O12 powders calcined
      at 800 degrees C. The sintered samples exhibit a giant dielectric constant,
      epsilon' of approximately 10(3)-10(4). The large low-frequency dielectric
      permittivity at low temperature is closely related to sub-grain boundary
      distribution, including conductivity effect. Furthermore, the ceramic shows three
      semicircles in the complex impedance plane. However, at low frequency,
      semicircles of sub-grain boundary and grain boundary are considered to represent
      collapse different electrical mechanisms. The another is ascribed to the
      contribution of grain. The dielectric behavior at several frequencies and
      temperatures of these samples can be attributed to electronic inhomogeneities
      present in material and can be explained based on a microstructural model.

PMID- 22400242
TI  - Polyisoprene-multi wall carbon nanotube composite structure for flexible pressure
      sensor application.
AB  - The major problem of conventional rigid sensor materials is difficulty to integer
      them into soft flexible structures. Piezoresistive polyisoprene/nanostructured
      carbon composite appears as promising materials for such application. Previous
      research approved high structure carbon black and carbon nanotube filled
      composites as finger pressure sensitive piezoresistive materials. Carbon
      nanotubes originate with variable length to width ratio and high electric
      conductivity in longitudinal direction of the tubes, which theoretically should
      make it possible to obtain electric percolation in polymercarbon nanotube
      composites at very low loads of filler. However recent experience with
      mechanically dispersed carbon nanotubes shows quite high values of percolation
      threshold and specific sensing properties. In this work we present an attempt to
      use ultrasound for improved dispersion of the filler in a piezoresistive
      polyisoprene-multi wall carbon nanotube composite as well polyisoprene-high
      structure carbon black composite. The noticeable shift of percolation threshold
      for both types of composites have been achieved. The piezoresistive behavior of
      sonicated composites have been determined and compared with mechanically mixed
      ones. The differences have been evaluated and explained.

PMID- 22400243
TI  - Mechanical properties of Pt-Ir and Ni-Ir binary alloys for glass-molding dies
      coating.
AB  - In this study, the different compositions of Pt-Ir and Ni-Ir alloys were
      deposited by utilizing ion source assisted magnetron sputtering system (ISAMSS).
      The surface roughness and crystallite size of the Pt-Ir and Ni-Ir coatings were
      analyzed by atomic force microscopy (AFM) and X-ray diffraction (XRD),
      respectively. In addition, coatings were soaked at 700 degrees and maintained 10
      min under N2 atmosphere using a glass-molding machine. The annealed coatings for
      oxidation test were examined by energy dispersive X-ray spectrometry (EDS) and
      for microhardness and reduced modulus test were evaluated by nanoindentation
      instrucment. The cross-sectional structures between the Pt-Ir and Ni-Ir coating
      layer and substrates were also examined by field emission scanning electron
      microscope (FESEM). The results show that surface roughness Ra from 1.25 nm to
      3.426 nm was observed with increasing the Ni elements. However, the Ra is less
      than 2 nm measured in Ir-based coatings doped with Pt concentrations under this
      study. With increasing Pt and Ni doping, the microhardness of both coatings
      decreased significantly and the values of reduced modulus of Pt-Ir alloys are
      larger than that of Ni-Ir alloys. After oxidation process, the oxygen
      concentration of Pt-Ir coatings is less than that of Ni-Ir coatings and the Pt-Ir
      coatings exhibit superior properties including oxidation resistance, low surface
      roughness and high reduced modulus over Ni-Ir coatings, especially for the high
      Pt concentration coatings such as Pt-Ir 2 (55.25 at.% Pt) and Pt-Ir 3 (79.42 at.%
      Pt) coatings. The surface roughnesses of all specimens annealed at 700 degrees C
      were slightly larger than as-deposited coatings. Moreover, due to the serious
      oxidation occurred in Ni-Ir 3 (73.45 at.% Ni) coatings, the value of reduced
      modulus of this specimen coating is the lowest and the corrsponding Ra value is
      the largest compared with the rest of Ir-based coatings in the oxidation testing.

PMID- 22400244
TI  - Organic-inorganic nanocomposites of methylcellulose as a precursor of
      nanocrystalline ZnO layers.
AB  - In this article, we present a sol-gel method to synthesize hybrid nanocomposite
      films of Zinc oxide (ZnO)/methylcellulose (MC) on microscope glass slides. The
      zinc/MC solutions were prepared, using different weight ratios of zinc acetate
      dihydrate to MC, in the presence of acetic acid. Fourier transform infrared
      spectroscopy (FTIR) investigation of the Zn sol/MC mixture showed coordinating
      interaction between zinc ions and MC. Thermal gravimetry analysis (TGA) results
      showed rapid decomposition of organic compounds in the composites at the
      temperature range of 200-450 degrees C. The UV-Vis spectroscopy was also utilized
      to identify ZnO nanoparticles in the MC matrix. The generation of ZnO
      nanoparticles in the MC matrix was then observed to proceed in situ through the
      annealing of the gel phase at 200 degrees C. Nanocrystalline films of ZnO/MC were
      subsequently obtained by the calcinations of ZnO/MC nanocomposites at 550 degrees
      C. The nanocomposite films were transparent in the visible light and showed a
      higher energy absorption edge compared with the bulk ZnO. Nanocrystallite sizes
      of ZnO particles were estimated from scanning electron microscopy (SEM) and the X
      ray diffraction (XRD) investigations.

PMID- 22400245
TI  - High performance of GaN-based flip-chip light-emitting diodes with hole-shape
      patterned ITO ohmic contact layer and AgIn reflector.
AB  - The enhancement of light extraction efficiency is observed when the hole-shape
      patterned ITO ohmic contact layer and AgIn reflector is adopted in GaN-based flip
      chip (FC) light emitting diodes (LEDs). ITO layer (140 nm) and AgIn (200 nm) was
      deposited on the top of p-GaN by in-line DC sputtering and electron beam
      evaporating system, respectively. The ITO ohmic contact layer showed a low
      specific contact resistance of 2.66 x 10(-5) Omega cm(-2) and high transmittance
      of >85% at visible spectral regions. The AgIn reflector exhibited a low specific
      contact resistance of 1.90 x 10(-5) Omega cm(-2) and high reflectance of
      approximately 84% at visible spectral regions. Comparing with unpatterned
      ITO/AgIn layer, the optical output power of GaN-based FC LEDs improves
      approximately 30% by the adoption of micro size hole-shape patterned ITO ohmic
      contact layer and AgIn reflector.

PMID- 22400246
TI  - Barium titanate thin films deposited by electrophoresis on p-Doped Si (001)
      substrates.
AB  - Barium titanate (BaTiO3) thin films have been prepared by electrophoretic
      deposition on p-doped and platinum covered silicon (Si) substrates. Their
      structure, nanostructure and dielectric properties were characterized. The as
      deposited films were polycrystalline and composed by barium titanate nanograins
      with an average grain size approximately 9 nm. Annealing at high temperatures
      promoted grain growth, so that the samples annealed at 600 degrees C presented
      average grain sizes approximately 24 nm. From Raman spectroscopy measurements it
      was found that the tetragonal (ferroelectric) BaTiO3 phase was stabilized on the
      films. Also, at higher annealing temperatures, cation disorder was reduced on the
      films. From measurements of the temperature dependence of the dielectric
      permittivity the corresponding paraelectric-ferroelectric phase transition was
      determined. The observed transition temperature (approximately 100 degrees C) was
      found to be below the BaTiO3 bulk or thick film values, due to the small
      nanosized grains composing the films.

PMID- 22400247
TI  - Nanostructured carbon beads--properties and biomedical applications.
AB  - In this study, amorphous carbonaceous nanoparticles were prepared by a simple
      hydrothermal process using glucose as precursor. The nearly perfect spherical
      particles (beads) with the dimensions in the range of 10-500 nm were obtained
      depending on the main process parameters (precursor concentration, temperature,
      and time). The particles size, surface morphology, structure, and composition
      have been examined by TEM, SEM, X-ray diffraction, XPS, FTIR and Raman
      spectroscopy. These amorphous carbonaceous nanobeads (a-CNBs) have been found
      nontoxic in vitro with a variety of cultured cell lines. The size-dependent
      effect of a-CNBs addition on cell function has been observed. For example, a-CNBs
      can, in some cases, substantially increase interleukin-12 (IL-12) production by
      bone marrow dendritic cells. It has been further demonstrated that a-CNBs can be
      modified with fluorescent dye molecules or loaded with anti-cancer drugs for
      bioimaging or therapeutic purposes, respectively. The results of these tests and
      the strategies for the particle preparation and functionalization for biomedical
      applications have been discussed.

PMID- 22400248
TI  - Dependence on temperature and energy of the heteroepitaxy of small metallic
      nanoclusters.
AB  - Deposition at different energies and temperatures of small metallic nanoclusters
      on metallic substrates is studied by molecular-dynamics simulations. Small-,
      Co/Cu(001), and large-misfit, Cu/Au(001) and Au/Cu(001), systems are considered.
      The rise in temperature improves the epitaxial order, although its effect is
      smaller in large-misfit systems. Thus, by increasing this parameter, non
      epitaxial clusters can turn their structure into epitaxial in the case of
      Co/Cu(001), into aligned in Cu/Au(001), and into layered in Au/Cu(001).
      Therefore, the characteristics of the alignment are determined by the properties
      of the material. In addition, the influence of the initial structure is more
      marked in Co and Cu clusters, since they can reproduce locally other phases.
      Epitaxy can also be improved if the deposition energy is increased, although the
      deposited cluster loses its original shape progressively. Its effect is different
      depending mainly on the degree of misfit. An increase in energy (of up to 0.75
      eV/atom) produces similar effects, but more noticeable, as a rise in temperature.

PMID- 22400249
TI  - Transient conductivity in nanostructured films.
AB  - The understanding of electron transfer across interfaces and nanostructures
      constitutes a major challenge in emerging nanodevices. Ultrafast injection of
      carriers through the interface at femtosecond scale has been reported in dye-TiO2
      systems and in piezotronics devices based on ZnO nanotubes, followed by anomalous
      transport of the charges through the nanoporous network. These features which
      could not be expected on the basis of bulk models, motivated real-time
      theoretical studies of the injection dynamics and transport at the nanoscale to
      improving the overall efficiency. In this paper correlation functions are
      evaluated by the Fourier transform of the frequency-dependent conductivity of the
      system. Drude-Lorentz and Schmith models, fitted to experimental data, have been
      analyzed. We present results for TiO2 and ZnO oxides nanostructured films. It is
      found that the diffusion coefficient of carriers is usually very small, but can
      reach values comparable to the single crystal at early times after carriers are
      released, even in the presence of structural disorder, under conditions
      concerning the size of the nanoparticles, the strength of the coupling of the
      charges with the nanoparticles and the relaxation time. Our result for the
      current-current correlation function as a function of time is in agreement with
      the obtained result by ultrafast time THz spectroscopy.

PMID- 22400250
TI  - Improving thermal barrier coatings by laser remelting.
AB  - Thermal barrier coatings are extensively used to protect metallic components in
      applications where the operating conditions include aggressive environment at
      high temperatures. These coatings are usually processed by thermal spraying
      techniques and the resulting microstructure includes thin and large splats,
      associated with the deposition of individual droplets, with porosity between
      splats. This porosity reduces the oxidation and corrosion resistance favouring
      the entrance of aggressive species during service. To overcome this limitation,
      the top coat could be modified by laser glazing reducing surface roughness and
      sealing open porosity. ZrO2(Y2O3) top coat and NiCrAlY bond coating were air
      plasma sprayed onto an Inconel 600 Ni base alloy. The top coat was laser remelted
      and a densified ceramic layer was induced in the top surface of the ceramic
      coating. This layer inhibited the ingress of aggressive species and delayed bond
      coat oxidation.

PMID- 22400251
TI  - Deposition of hybrid organic-inorganic composite coatings using an atmospheric
      plasma jet system.
AB  - The objective of this study is to investigate the influence of alcohol addition
      on the incorporation of metal oxide nanoparticles into nm thick siloxane
      coatings. Titanium oxide (TiO2) nanoparticles with diameters of 30-80 nm were
      incorporated into an atmospheric plasma deposited tetramethylorthosilicate (TMOS)
      siloxane coating. The TMOS/TiO2 coating was deposited using the atmospheric
      plasma jet system known as PlasmaStream. In this system the liquid
      precursor/nanoparticle mixture is nebulised into the plasma. It was observed that
      prior to being nebulised the TiO2 particles agglomerated and settled over time in
      the TMOS/TiO2 mixture. In order to obtain a more stable nanoparticle/TMOS
      suspension the addition of the alcohols methanol, octanol and pentanol to this
      mixture was investigated. The addition of each of these alcohols was found to
      stabilise the nanoparticle suspension. The effect of the alcohol was therefore
      assessed with respect to the properties of the deposited coatings. It was
      observed that coatings deposited from TMOS/TiO2, with and without the addition of
      methanol were broadly similar. In contrast the coatings deposited with octanol
      and pentanol addition to the TMOS/TiO2 mixture were significantly thicker, for a
      given set of deposition parameters and were also more homogeneous. This would
      indicate that the alcohol precursor was incorporated into the plasma polymerised
      siloxane. The incorporation of the organic functionality from the alcohols was
      confirmed from FTIR spectra of the coatings. The difference in behaviour with
      alcohol type is likely to be due to the lower boiling point of methanol (65
      degrees C), which is lower than the maximum plasma temperature measured at the
      jet orifice (77 degrees C). This temperature is significantly lower than the 196
      degrees C and 136 degrees C boiling points of octanol and pentanol respectively.
      The friction of the coatings was determined using the Pin-on-disc technique. The
      more organic coatings deposited with octanol and pentanol exhibited friction
      values of 0.2, compared with approx. 0.8 for the coatings deposited from
      TMOS/TiO2 mixture (with and without methanol). Wear performance comparison
      between the two types of coating again indicated a significant organic component
      in the coatings deposited from the higher boiling point alcohols.

PMID- 22400252
TI  - Drug delivery observation of hydrophobe ferrofluid and magnetite nanoparticals by
      SPring-8 synchrotron radiation.
AB  - In this study, the composite magnetic nanoparticles of coated SiO nano film with
      about 8 nm size and high saturation magnetization value, were synthesized by
      liquid phase precipitation method. The magnetic nanoparticles can be dispersed in
      various liquid media, widely known as magnetic fluids or ferrofluids with both
      magnetic and liquid properties. The materials been collected great interests and
      more and more attentions to focus into Drug Delivery System (DDS) as a new
      technology in this paper. We use the composite nanoparticles to disperse H2O and
      inject the solutions into rat's in-vivo organs. And, in the experiments by using
      a strong photon beam of SPring-8 Synchrotron Radiation facility, the distribution
      stat and the effects of magnetic field as well as drug delivery behaviour of
      nanoparticles in the rat' kidney are verified by the in-vivo observations.

PMID- 22400253
TI  - Gasochromic switching of Ta and Pd-doped nanocrystalline TiO2 thin films.
AB  - In this work TiO2:(Ta, Pd) thin films with gasochromic properties have been
      described. Thin films were prepared by reactive magnetron sputtering process
      using mosaic Ti-Ta-Pd target. The amounts of dopants were 2.54 at.% and 12.36
      at.% of Ta and Pd, respectively. The results of optical measurements performed at
      presence of ethanol and additional heating of the sample up to 350 degrees C have
      shown an abrupt change of transmission level from 80% down to 10% in VIS and in
      IR range. The gasochromic change was very fast. Moreover, rapid cooling (down to
      room temperature) in an air ambient results in stable thin film coloration. The
      reverse effect (bleaching) was obtained after annealing at 500 degrees C in an
      ambient air.

PMID- 22400254
TI  - Synthesis and characteristics of tb-doped Y2SiO5 nanophosphors and luminescent
      layer for enhanced photovoltaic cell performance.
AB  - Nanophosphors based on green emitting terbium doped yttrium silicates with the
      general formula Y2SiO5:Tb3+ with a size of 30-60 nm were synthesized by the
      hydrothermal method. The prepared nanophosphors were characterized by X-ray
      diffraction, field-emission scanning electron microscopy, transmission electron
      microscopy, UV-Vis diffuse reflectance spectroscopy and fluorescence
      spectroscopy. It was found that the nanophosphors crystallize in an X1-type
      monoclinic structure (P2(1)/c) and absorb UV light from 220 to 300 nm which they
      then down-convert into visible-light (strong green emission at around 545 nm (5D4
      ->7F(J. As TiO2-based dye-sensitized solar cells exhibit their maximum incident
      photon to current efficiency at around 500-600 nm, the wavelength-modulation
      characteristics of the nanophosphors can be efficient for dye-sensitized solar
      cell systems. Therefore, the Y2SiO5:Tb3+ nanophosphors were introduced into a
      TiO2-based dye-sensitized solar cell and their effects on the performance of the
      solar cell were investigated.

PMID- 22400255
TI  - Surface analysis and osteoblasts response of a titanium oxi-carbide film
      deposited on titanium by ion plating plasma assisted (IPPA).
AB  - Titanium is the most widely used material in orthopaedic and dental
      implantoprosthesis due to its superior physical properties and enhanced
      biocompatibility due to the spontaneous formation of a passivating layer of
      titanium oxides which, however, does not form good chemical bonds with bone and
      tends to brake exposing bulk titanium to harsh body fluids releasing titanium
      particles which may prime an inflammation response and a fibrotic tissue
      production. In order to avoid these possible problems and to enhance the
      biocompatibility of titanium implants, modifications of titanium surfaces by many
      different materials as hydroxyapatite, titanium nitride, titanium oxide and
      titanium carbide have been proposed. The latter is shown to be an efficient
      protection for the titanium implant in the harsh conditions of biological tissues
      and, compared to untreated titanium, acting like an osteoblast stimulation factor
      increasing in vitro production of proteins involved in osteogenesis. These
      results were confirmed by in vivo experiments in rabbits: implants covered by the
      titanium carbide (TiC) layer were faster and better osseointegrated than
      untreated titanium implants. The TiC layer was deposited by a Pulsed Laser
      Deposition (PLD) device which allowed only one deposition per cycle, shown to be
      unsuitable for industrial applications. Therefore the main objective of the
      present work was to replace PLD process with an Ion Plating Plasma Assisted
      (IPPA) deposition process, which is suitable for industrial upgrading. By this
      technique, nanostructured TiOx-TiCy-C has been deposited on titanium after
      sandblasting with 120 micron zirconia spheres. XPS analyses revealed the presence
      of about 33% carbon (50% of which is present as free carbon), 39% oxygen and 28%
      titanium (37% of which is bound to carbon to form TiC and 63% is bound to oxygen
      to form non stoichiometric oxides). Surface mechanical response of as-deposited
      coatings has been performed by nanoindentation techniques. Focused Ion Beam
      micrographs showed bigger differences on the obtained nanostructure compared to
      the PLD coating structure; in vitro tests confirm for IPPA produced coatings an
      improvement in stimulating osteoblasts to produce mRNA's of proteins involved in
      the ossification process, this latter case they resulted to be faster and more
      efficient. The proposed treatement is expected to improve the good results
      obtained by PLD, in vivo as well.

PMID- 22400256
TI  - Nanostructured Ag platforms as biosensors of nucleobase chains.
AB  - Nanostructured Ag platforms have been obtained by simple chemical procedure and
      characterized by AFM (atomic force microscopy) measurements, for use in
      biosensing by means of SERS (surface-enhanced Raman scattering) spectroscopy. The
      SERS efficiency of these substrates has been verified by microRaman measurements
      on small RNA chains with different nucleobase content, showing sensitivity near
      attomole level. It is our opinion that these metal substrates may be widely used
      as appropriate sensors for detecting biomolecules in many applications concerning
      medical diagnostics, pharmacological research and nanomaterials technology.

PMID- 22400257
TI  - Nafion electro-spun reinforced membranes for polymer electrolyte fuel cell.
AB  - The introduction of different reinforcement materials (yarns, fibrils, etc) into
      the membranes has been investigated with the aim of maintaining adequate membrane
      properties in terms of mechanical strength, good chemical stability, low swelling
      at critical temperatures and a stable electrochemical performance in PEFC. An
      innovative technique for the development of membranes is based on polymeric films
      containing polymeric nanofibres obtained through electrospinning. The
      electrospinning of Nafion blends with polyvinylpirrolidone (PVP) and polystyrene
      (PS) was investigated in this work. In particular, the morphology and diameter of
      electrospun fibres as a function of the electrospinning parameters and solution
      preparation have been studied and in both cases, a critical concentration of
      blend solution was found. Beaded fibres were obtained above such a concentration
      and, below it, only fibre mats were observed. Reinforced Nafion-based membranes
      were realised by using the obtained spun films. Preliminary proton conductivity
      and fuel cell results have shown the capability of operating in a fuel cell
      environment with a slightly higher performance than pure Nafion but having an
      improved stability at high temperatures.

PMID- 22400258
TI  - Nano structured physical vapor deposited coatings by means of picosecond laser
      radiation.
AB  - Molding of nano structures by injection molding leads to special requirements for
      the tools e.g., wear resistance and as low as possible release forces of the
      molded components. On the other hand it is not allowed to affect the replication
      precision. Physical vapor deposition is one of the promising technologies for
      applying coatings with adapted properties like high hardness, low roughness, low
      Young's modulus and less adhesion to the plastics melt. Although physical vapor
      deposition technology allows the deposition of films on micro structures without
      changing the structure significantly, film deposition on nano structures and
      small micro structures leads to a relevant change in surface topography. For this
      reason direct structuring of physical vapor deposition coatings might be
      beneficial. In this paper structuring was done using a picoseconds ultraviolet
      laser, Lumera Laser "Rapid," with a master oscillator power amplifier system at
      355 nm. Two different coatings were deposited by magnetron sputter ion plating
      physical vapor deposition technology for laser structuring tests ((Cr, Al)N, (Cr,
      Al,Si)N). After deposition, the coatings were analyzed by common techniques
      regarding hardness, Young's modulus and morphology. The structures were analyzed
      by scanning electron microscopy. The results show a high potential for laser
      structuring of coatings deposited via physical vapor deposition. Linear
      structures with sizes between 400 nm and 10microm were realized.

PMID- 22400259
TI  - Crystalline gamma-Al2O3 physical vapour deposition-coating for steel thixoforging
      tools.
AB  - The process of thixoforming, which has been part of many researches during the
      last decades, combines the advantages of forging and casting for the shaping of
      metallic components. But due to the high temperatures of semi-solid steel alloys
      high demands on the tools are requested. To resists the thermal and mechanical
      loads (wear, friction, thermal and thermomechanical fatigue) protecting thin
      films are necessary. In this regard crystalline gamma-Al2O3 deposited via
      Physical Vapour Deposition (PVD) is a promising candidate: It exhibits high
      thermal stability, high oxidation resistance and high hot hardness. In the
      present work the application of a (Ti, Al)N/gamma-Al2O3 coating deposited by
      means of Magnetron Sputter Ion Plating in an industrial coating unit is
      presented. The coating was analysed by means of Rockwell test, nanoindentation,
      and Scanning Electron Microscopy (SEM). The coated tool was tested in
      thixoforging experiments with steel grade X210CrW12 (AlSI D6). The surface of the
      coated dies was examined with Scanning Electron Microscope (SEM) after 22, 42, 90
      and 170 forging cycles.

PMID- 22400260
TI  - A self-defined hollow needle formation on silicon membranes with the aids of
      carbon nanotubes.
AB  - A self-defined method for the formation of hollow needles and micro-cylindrical
      structures on silicon substrates is reported which uses the combination of high
      aspect ratio vertical etching of silicon with a small angle vacuum deposition
      technique. These structures can be used as the media to transfer gas and liquid
      through their tiny holes. The fabrication is further continued with the growth of
      carbon nanotubes on the already created silicon-based features to form a cage
      like cylindrical structure. In addition, the growth of vertical carbon nanotubes
      just inside the cup-like structures has been demonstrated without a need for an
      extra lithography step.

PMID- 22400261
TI  - Influence of the N2 partial pressure on the characteristics of CrZrN coatings
      synthesized Using a segment CrZr target.
AB  - In this study, CrZrN films were synthesized by unbalanced magnetron sputtering
      (UBM) under various N2 partial pressures and their characteristics such as
      crystalline structure, surface morphology, microstructure and mechanical
      properties as a function of the N2 partial pressures were analyzed by X-ray
      diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy
      (AFM), nanoindentation, wear tests, and corrosion tests. Results revealed that,
      with increasing the N2 partial pressure from 0.05 to 0.21 Pa, the nitrogen
      content of the films increased from approximately 40.9 to 53.7 at%, the
      deposition rate decreased from approximately 100 to 59 nm/min and the surface
      roughness (Rms value) was increased from approximately 0.57 to 1.79 nm. The
      Cr37.3-Zr9.0-N53.7 film has the highest hardness, elastic modulus, and plastic
      deformation resistance of 36 GPa, 380 GPa, and 0.41, respectively. The Cr37.3
      Zr9.0-N53.7 film also has the lowest friction coefficient and wear rate of 0.19
      and 3.01 (10(-6)m3/Nm) at room temperature. In addition, the potentiodynamic test
      results showed the corrosion resistance of the CrZrN films became increased
      significantly and their corrosion current density (i(corr)), corrosion potentials
      (Ecorr) and corrosion rate decreased with increasing N2 partial pressure.

PMID- 22400262
TI  - Study of bi-enzyme immobilization onto layered double hydroxides nanomaterials
      for histamine biosensor application.
AB  - In this work, we present the development of a hybrid biomembrane based on the
      immobilization of diamine oxidase (DAO) into LDH thin films for histamine
      detection. The LDHs preselected as host matrixes are: hydrotalcites
      (Mg2Al(CO3)0.5(OH)6), lowaite (Mg4Fe(OH)10Cl) and hydrocalumite (Ca2Al(OH)6Cl).
      The immobilized probes were characterized by atomic force microscopy (AFM) and
      attenuated total reflection infrared spectroscopy (IR-ATR mode). The analysis of
      these results shows that the immobilization of DAO occurs with all type of
      selected LDH and is stable after a 7 day-immersion in phosphate buffer solution.
      The LDH incorporating magnesium or calcium divalent cations present high-quality
      surface topology for DAO immobilization and the ability to keep the enzyme in a
      well conformation for biogenic amines catabolism and histamine detection.

PMID- 22400263
TI  - Platinum-gold nanoclusters as catalyst for direct methanol fuel cells.
AB  - Nanosized platinum-gold alloys clusters have been deposited on gas diffusion
      electrode by sputter deposition. The deposits were characterized by FE-SEM, TEM
      and XPS in order to verify the formation of alloy nanoparticles and to study the
      influence of deposition technique on the nanomorphology. The deposition by
      sputtering process allowed a uniform distribution of metal particles on porous
      surface of carbon supports. Typical island growth mode was observed with the
      formation of a dispersed metal nanoclusters (mean size about 5 nm). Cyclic
      voltammetry was used to determine the electrochemical active surface and the
      electrocatalytic performance of the PtAu electrocatalysts for methanol oxidation
      reaction. The data were re-calculated in the form of mass specific activity
      (MSA). The sputter-catalyzed electrodes showed higher performance and stability
      compared to commercial catalysts.

PMID- 22400264
TI  - Electrocatalysts for methanol oxidation based on platinum/carbon nanofibers
      nanocomposite.
AB  - New carbon nanomaterials, i.e., carbon nanotubes and nanofibers, with special
      physico-chemical properties, are recently studied as support for methanol
      oxidation reaction electrocatalysts replacing the most widely used carbon black.
      Particularly, carbon fibrous structures with high surface area and available open
      edges are thought to be promising. Platelet type carbon nanofibers, which have
      the graphene layers oriented perpendicularly to the fiber axis, exhibit a high
      ratio of edge to basal atoms. Different types of carbon nanofibers (tubular and
      platelet) were grown by plasma enhanced chemical vapour deposition on carbon
      paper substrates. The process was controlled and optimised in term of growth
      pressure and temperature. Carbon nanofibers were characterised by high resolution
      scanning electron microscopy and X-ray photoelectron spectroscopy to assess the
      morphological properties. Then carbon nanofibers of both morphologies were used
      as substrates for Pt electrodeposition. High resolution scanning electron
      microscopy images showed that the Pt nanoparticles distribution was well
      controlled and the particles size went down to few nanometers. Pt/carbon
      nanofibers nanocomposites were tested as electrocatalysts for methanol oxidation
      reaction. Cyclic voltammetry in H2SO4 revealed a catalyst with a high surface
      area. Cyclic voltammetry in presence of methanol indicated a high electrochemical
      activity for methanol oxidation reaction and a good long time stability compared
      to a carbon black supported Pt catalyst.

PMID- 22400265
TI  - Atomic layer deposition of aluminum oxide films for carbon nanotube network
      transistor passivation.
AB  - Ultra-thin (2-5 nm thick) aluminum oxide layers were grown on non-functionalized
      individual single walled carbon nanotubes (SWCNT) and their bundles by atomic
      layer deposition (ALD) technique in order to investigate the mechanism of the
      coating process. Transmission electron microscopy (TEM) was used to examine the
      uniformity and conformality of the coatings grown at different temperatures (80
      degrees C or 220 degrees C) and with different precursors for oxidation (water
      and ozone). We found that bundles of SWCNTs were coated continuously, but at the
      same time, bare individual nanotubes remained uncoated. The successful coating of
      bundles was explained by the formation of interstitial pores between the
      individual SWCNTs constituting the bundle, where the precursor molecules can
      adhere, initiating the layer growth. Thicker alumina layers (20-35 nm thick) were
      used for the coating of bottom-gated SWCNT-network based field effect transistors
      (FETs). ALD layers, grown at different conditions, were found to influence the
      performance of the SWCNT-network FETs: low temperature ALD layers caused the
      ambipolarity of the channel and pronounced n-type conduction, whereas high
      temperature ALD processes resulted in hysteresis suppression in the transfer
      characteristics of the SWCNT transistors and preserved p-type conduction. Fixed
      charges in the ALD layer have been considered as the main factor influencing the
      conduction change of the SWCNT network based transistors.

PMID- 22400266
TI  - Synthesis and structure analysis of La0.5SR0.5TiO3 nanoparticles prepared by
      thermal decomposition method.
AB  - La0.5Sr0.5TiO3 (LSTO) nanoparticles were synthesized by thermal decomposition
      method using Cl3La, CI2Sr x 6H2O and C16H28O6Ti as starting materials. The
      obtained precursor in a powder form was calcined at 700, 900, 1100 and 1300
      degrees C for 3, 6 and 9 h in air. The structures of all samples were analyzed by
      XRD and some of them were taken for SEM, TEM and VSM measurements. The results
      from SEM showed the parallelpipe like shape of the particles with sizes
      distributed between 80 and 180 nm and the sizes of these particles were increased
      with the increasing of calcination temperature and time. The XRD's results showed
      the perovskite structure with the lattice type of orthorhombic at the calcination
      temperature of 900, 1100 and 1300 degrees C for 3, 6 and 9 h. The TiO and others
      unknown phase were found at low calcination temperature and they were disappeared
      as the calcination temperature and time were increased. The results of TEM
      support the orthorhombic structure of LSTO nanoparticles with crystallite size
      less than 200 nm as revealed by SEM and XRD. The magnetic property of all samples
      was measured by VSM and revealed that those prepared at 700, 900, and 1100
      degrees C exhibit diamagnetic behavior, whereas one at 1300 shows ferromagnetism
      at room temperature. In this work, it is found that the nano-LSTO of high
      crystalline phase and purity can be prepared by thermal decomposition method at
      calcination temperature of 900 to 1300 degrees C in air for 6-9 h.

PMID- 22400267
TI  - Synthesis and characterization of high purity hydroxyapatite nanorods by
      hydrothermal technique.
AB  - High purity hydroxyapatite (HAp) nanorods were synthesized by hydrothermal
      technique using Ca(NO3)2 x 4H2O and (NH4)2HPO4 as starting materials in a
      hydrothermal reactor at 150-200 degrees C for 12-24 h with pH6 and pH9.5,
      respectively. The prepared HAp nanorods were characterized by XRD, FTIR, and TEM
      techniques. The XRD results confirmed the formation of pure phase of HAp at
      pH9.5. With increasing temperature and time, the crystallinity of the HAp was
      increased, showing the hexagonal structure of HAp with the lattice parameter a in
      a range of 1.144-1.148 nm and c of 0.723-0.724 nm. The crystalline sizes of the
      powders were found to be 44-85 nm as evaluated by the XRD line broadening
      technique. The chemical compositions of the HAp nanorods were characterized by
      FTIR spectroscopies. The peaks of the phosphate carbonate and hydroxyl vibration
      modes were observed in the FTIR spectra for all the samples. The morphology of
      the HAp was nanorods of diameter less than 100 nm, as revealed by TEM. Increasing
      the temperature and time resulted in the transition from polycrystalline to
      single crystalline phase of the HAp, as clearly confirmed by the analysis of TEM
      diffraction patterns.

PMID- 22400268
TI  - Fantastic improvement in quality and quantity of carbon nanotubes synthesized on
      Al2O3-SiO2 supports by N2 pretreatment.
AB  - The raw materials, condition and the method of preparing the catalysts play an
      important role in the growth of high quality Carbon Nanotubes by Catalytic
      Chemical Vapor Deposition method. In this work, the efficiency of Carbon
      Nanotubes growth was increased by a simple controlled preheating of the catalyst
      in N2 atmosphere. Supports were prepared by mixing alumina powder with tetraethyl
      orthosilicate (TEOS) by a chemical method at low temperature. Afterwards, the
      supports were impregnated with iron. The dried and ground catalyst was heated in
      N2 atmosphere at 500 degrees C for 1 hour followed by cooling down to room
      temperature. Methane was passed over the prepared catalyst bed at 900 degrees C.
      Supports, supported catalysts and Carbon Nanotubes samples have been
      characterized by Transmission Electron Microscopy, Scanning Electron Microscopy,
      Gas Adsorption/Desorption Analysis, X-Ray Diffraction and Raman Spectroscopy.
      Scanning Electron Microscopy images of the nanotubes showed a drastic increase in
      the growth rate, length and straightness of the Nanotubes in comparison to the
      growth without preheating and even preheating in air atmosphere. Raman
      Spectroscopy of the samples and Transmission Electron Microscopy pictures showed
      bundles, mostly equi-diameter Single Wall Nanotubes. In fact, the growth rate,
      length, and purity of the Nanotubes, also the homogeneity of the tubes improved.
      The conclusion can be made with the help of proposed theory of nucleation and
      growth of Nanotubes based on comparative results of the characterizations with
      and without preheat-treatment. It seems that the preheat-treatment in N2 affected
      the catalyst structure and its interaction with support as well as distribution
      of the catalyst particles on the support. These changes in return affect the
      quality and quantity of final production.

PMID- 22400269
TI  - Membrane selectivity versus sensor response in hydrogenated amorphous silicon
      CHEMFETs using a semi-empirical model.
AB  - Toxic amides, such as acrylamide, are potentially harmful to Human health, so
      there is great interest in the fabrication of compact and economical devices to
      measure their concentration in food products and effluents. The CHEmically
      Modified Field Effect Transistor (CHEMFET) based on amorphous silicon technology
      is a candidate for this type of application due to its low fabrication cost. In
      this article we have used a semi-empirical model of the device to predict its
      performance in a solution of interfering ions. The actual semiconductor unit of
      the sensor was fabricated by the PECVD technique in the top gate configuration.
      The CHEMFET simulation was performed based on the experimental current-voltage
      curves of the semiconductor unit and on an empirical model of the polymeric
      membrane. Results presented here are useful for selection and design of CHEMFET
      membranes and provide an idea of the limitations of the amorphous CHEMFET device.
      In addition to the economical advantage, the small size of this prototype means
      it is appropriate for in situ operation and integration in a sensor array.

PMID- 22400270
TI  - Nanostructuring of ultra-thin HfO2 layers for high-k/III-V device application.
AB  - We report on the nanopatterning by electron beam lithography (EBL) and reactive
      ion etching (RIE) in a SF6/Ar+ plasma of ultra-thin HfO2 films deposited on GaAs
      (001) substrates for gate oxide application in next generation III-V metal-oxide
      semiconductor field effect transistors (MOSFETs). Characterization of the
      HfO2/GaAs nanostructured samples by atomic force microscopy (AFM), high
      resolution scanning electron microscopy (HRSEM), energy-dispersive X-ray
      spectroscopy microanalysis (EDX) and transmission electron microscopy (TEM) has
      shown the formation of well defined HfO2 patterns with nanometre-scale linewidth
      control and anisotropic profiles. In addition, atomically smooth, stoichiometric
      and residue-free bottom GaAs etched lines with a lateral dimension of
      approximately 50 nm have been demonstrated.

PMID- 22400271
TI  - Microstructure and thermal behaviour of plasma sprayed zirconia/alumina composite
      coating.
AB  - In thermal barrier coatings (TBC), failure occurs near or at the interface
      between the metallic bondcoat and topcoat. On high temperature conditions, an
      oxide scale which is named thermally grown oxide (TGO) occurs along the
      bond/topcoat interface. For diminishing the creation of TGO, a dense coating with
      low residual stress and thermal stress buffer layer was preferable. High hardness
      ceramic coatings could be obtained by gas tunnel type plasma spraying, and the
      deposited coating had superior property in comparison with those deposited by
      conventional type plasma spray method. In this study, the gas tunnel type plasma
      spraying system was utilized to produce a zirconia/alumina functionally graded
      thermal barrier coating and discussed its physical and mechanical properties,
      thermal behavior and high temperature oxidation resistance of the coating are
      discussed. Consequently, the proposed system exhibited superior mechanical
      properties and oxidation resistance at the expenses of a slightly lower thermal
      insulating effect. This interlayer is preferred in order to minimize the
      detrimental effect of the phase transformation of gamma-Al2O3 to alpha-Al2O3.

PMID- 22400272
TI  - Effects of thermal annealing in oxygen plasma for buffer layers on properties of
      ZnO thin films.
AB  - ZnO thin films with ZnO buffer layers were grown by plasma-assisted molecular
      beam epitaxy (PA-MBE) on p-type Si(100) substrates. Before the growth of the ZnO
      thin films, the ZnO buffer layers were deposited on the Si substrates for 20
      minutes and then annealed at the different substrate temperature ranging from 600
      to 800 degrees C in oxygen plasma. The structural and optical properties of the
      ZnO thin films have been investigated by X-ray diffraction (XRD), scanning
      electron microscopy (SEM), and room-temperature (RT) photoluminescence (PL). A
      narrower full width at half maximum (FWHM) of the XRD spectra for ZnO(002) and a
      larger grain are observed in the samples with the thermal annealed buffer layers
      in oxygen plasma, compared to those of the as-grown sample. The surface
      morphology of the samples is changed from rugged to flat surface. In the PL
      spectra, near-band edge emission (NBEE) at 3.2 eV (380 nm) and deep-level
      emission (DLE) around 1.77 to 2.75 eV (700 to 450 nm) are observed. By increasing
      the annealing temperatures up to 800 degrees C, the PL intensity of the NBEE peak
      is higher than that of the as-grown sample. These results imply that the
      structural and optical properties of ZnO thin films are improved by the annealing
      process.

PMID- 22400273
TI  - On the influence of residual stress on nano-mechanical characterization of thin
      coatings.
AB  - In the present paper, the effect of residual stress on the mechanical behavior of
      thin hard coatings has been investigated by a new methodology based on the
      combined use of focused ion beam (FIB) micro-machining techniques and
      nanoindentation testing. Surface elastic residual stress were determined by
      nanoindentation testing on Focused Ion Beam (FIB) milled micro-pillars. The
      average residual stress present in a 3.8 microm CAE-PVD TiN coating on WC-Co
      substrate was calculated by the comparison of two different sets of load-depth
      curves, the first one obtained at centre of stress relieved pillars, the second
      one on the undisturbed (residually stressed) surface. Results for stress
      measurement were in good agreement with the estimate obtained by XRD (sin2 psi
      method) analysis on the same sample, adopting the same elastic constants. In
      addition, nanoindentation on stress relieved pillars also allowed to perform a
      more accurate evaluation of elastic modulus and hardness of the coating. The
      effect of residual stress on crack propagation modes was quantitatively analyzed
      by high-load nanoindentation and application of energy methods for fracture
      toughness evaluation. It is found that compressive residual stress plays a
      relevant role in determining the fracture behavior and failure modes of the
      coating. Finally, Microstructural observations of the deformation mechanisms of
      the TiN coating were performed by TEM analysis on the cross section of the
      indentation, obtained by FIB lamella thinning. Results showed that plastic
      deformation at the nanoscale essentially occurs by formation of shear bands
      inside the columnar grains, independently of residual stress. A transition
      between intra-granular shear deformation and columnar grain sliding is also
      observed as a function of the applied load.

PMID- 22400274
TI  - Nanocomposites for advanced fuel cell technology.
AB  - NANOCOFC (Nanocomposites for advanced fuel cell technology) is a research
      platform/network established based on the FP6 EC-China project www.nanocofc.org.
      This paper reviews major achievements on two-phase nanocomposites for advanced
      low temperature (300-600 degrees C) solid oxide fuel cells (SOFCs), where the
      ceria-salt and ceria-oxide composites are common. A typical functional
      nanocomposite structure is a core-shell type, in which the ceria forms a core and
      the salt or another oxide form the shell layer. Both of them are in the nano
      scale and the functional components. The high resolution TEM analysis has proven
      a clear interface in the ceria-based two-phase nanocomposites. Such interface and
      interfacial function has resulted in superionic conductivity, above 0.1 S/cm at
      around 300 degrees C, being comparable to that of conventional SOFC YSZ at 1000
      degrees C. Against conventional material design from the structure the advanced
      nanocomposites are designed by non-structure factors, i.e., the interfaces, and
      by creating interfacial functionalities between the two constituent phases. These
      new functional materials show indeed a breakthrough in the SOFC materials with
      great potential.

PMID- 22400275
TI  - Fabrication of silica-based multilayer films with self-cleaning and
      antireflective properties.
AB  - The silica-based multilayer films exhibiting both self-cleaning property and
      antireflection in the visible and near infrared regions have been deposited onto
      glass substrate by layer-by-layer deposition of PAH/PAA polyelectrolyte bilayers,
      followed by sequential deposition of PAH/SiO2 nanocomposite layers to create the
      nanoporous structure in the film, and finally treating with fluorosilane. To
      obtain the appropriate porosity and surface roughness so as to satisfy both
      antireflection and self-cleaning properties, the deposition of PAH/SiO2
      nanocomposite layers was varied from 2 to 8 layers. Scanning electron microscopy
      and atomic force microscopy analysis revealed that a highly nanoporous structure
      was obtained from the more deposition of loosely agglomerated SiO2 nanoparticles
      which increased with the increased cycle of PAH/SiO2 deposition. The film
      consisting of 6 and 8 PAH/SiO2 layers exhibited a very low reflection of only 1
      2% in the visible region and approximately 2-4% in the near infrared region, a
      maximum transmittance of approximately 93% in the visible region and
      approximately 94% in the near infrared region, and a high advancing contact angle
      of approximaetly 150 degrees. It is anticipated that the film which exhibited
      both self-cleaning and antireflection properties enables the application of the
      antireflection coatings under humid environments.

PMID- 22400276
TI  - Nanostructure of vortex during explosion welding.
AB  - The microstructure of a bimetallic joint made by explosion welding of
      orthorhombic titanium aluminide (Ti-30Al-16Nb-1Zr-1Mo) with commercially pure
      titanium is studied. It is found that the welded joint has a multilayered
      structure including a severely deformed zone observed in both materials, a
      recrystallized zone of titanium, and a transition zone near the interface.
      Typical elements of the transition zone-a wavy interface, macrorotations of the
      lattice, vortices and tracks of fragments of the initial materials-are
      determined. It is shown that the observed vortices are formed most probably due
      to local melting of the material near the contact surface. Evidence for this
      assumption is deduced from the presence of dipoles, which consist of two vortices
      of different helicity and an ultrafine duplex structure of the vortex. Also, high
      mixing of the material near the vortex is only possible by the turbulent
      transport whose coefficient is several orders of magnitude larger than the
      coefficient of atomic diffusion in liquids. The role played by fragmentation in
      both the formation of lattice macrorotations and the passage of coarse particles
      of one material through the bulk of the other is determined.

PMID- 22400277
TI  - The effect of Si nano-columns in 2-D and 3-D on cellular behaviour:
      nanotopography-induced CaP deposition from differentiating mesenchymal stem
      cells.
AB  - Si nano-columns were deposited in 2-D and 3-D in the form of well-defined
      geometries by physical vapor deposition. The films were grown by e-beam
      evaporation with an angle between source and substrate. The Si nano-columns were
      deposited in the shape of spiral with two different incoming atomic flux angle so
      that the manipulation of nano-columns in 3-D (out-of-plane) was obtained. The Si
      nano-columns were also grown as vertical stick with square, triangle and linear
      cross sections in 2D (in-plane). Rat bone marrow mesenchymal stem cells (MSCs)
      were cultured on these different Si nanosurfaces. MTS assay was carried out to
      determine the cell proliferation and viability based on different
      nanotopographies. For the evaluation of cell distribution and morphology, a SEM
      (Scanning Electron Microscopy) analysis was performed. Any CaP deposition on Si
      nanosurfaces was observed using energy dispersive X-Ray spectroscopy in SEM (SEM
      EDX). After 4 days of culture, there was a higher value of cell proliferation on
      square columns and spiral Si nano-columns grown with 85 degrees of incoming
      atomic flux. The cell attachment and spreading was also affected by the geometry
      of Si nano-columns. While there were still cells showing round/spherical
      morphology with minimal spreading on conventional Si surfaces, most of the cells
      cultured on different Si nanotopographies attached on the surface and displayed
      flattened morphology, especially on the square columns surface. Moreover, CaP
      deposition was discovered on square columns and spiral films with 85 degrees
      substrate angle. So, it can be concluded that there is a clear correlation
      between cell responses and nano-sized geometry on Si surface and it is possible
      to induce cellular differentiation and CaP formation in certain geometrical
      constraints.

PMID- 22400278
TI  - Solubilization of multi walled carbon nanotubes under a facile and mild
      condition.
AB  - Multi-walled carbon nanotubes (MWCNTs) functionalized with amino groups was
      prepared via chemical modification of carboxyl groups introduced on the carbon
      nanotube surfaces. Oxidation of MWCNTs was performed with ozone in aqueous phase
      and amidation of generated carboxylic groups, was occurred with amines in the
      presence of HATU as a coupling agent. Obtained functionalized MWCNTs are soluble
      in many common organic solvents. The functionalized MWCNTs were characterized in
      detail using FTIR-ATR, Raman CHN and SEM methods.

PMID- 22400279
TI  - Structure and magnetic properties of nanostructured Pd-Fe thin films produced by
      pulse electrodeposition.
AB  - Nanostructured Pd-Fe thin films with varied Fe content were prepared by
      electrodeposition technique from organic electrolytes on Cu and brass substrates.
      The structure and the magnetic properties of the films were investigated prior to
      post-deposition annealing. The structure of the Pd1-xFe(x) thin film with x =
      0.14, 0.24, and 0.52 was determined by X-ray diffraction (XRD) and transmission
      electron microscopy (TEM) as a solid solution of iron in palladium face-centered
      cubic lattice with the (111) orientation of nanograins relatively to the
      substrate surface. The films with higher iron concentration, x = 0.74, 0.91, have
      structure of a solid solution based on the body-centered cubic lattice. The
      average grain size determined by the scanning electron microscopy (SEM) for the
      first two alloys is 7-10 nm, and for the latter ones it is about 120 nm. The
      saturation magnetization of the films has linear dependence on the iron content,
      but coercivity has non-monotonic dependence on x, i.e., the films with x = 0.68
      show highest coercivity. The magnetic anisotropy of the samples is studied by
      ferromagnetic resonance (FMR) spectroscopy.

PMID- 22400280
TI  - Nanocrystalline graphite films nucleation by the radio frequency bias
      pretreatment.
AB  - New method for nucleation of different nanocrystalline carbon films upon
      monocrystalline Si substrate was proposed. The process is based on a combination
      of microwave and radio frequency plasma assisted chemical vapor deposition
      methods. Potential of the method for nucleation was demonstrated by deposition of
      nanocrystalline diamond film in pure microwave plasma in one process, immediately
      after "seeding" procedure. The method was also used for growth of nanocrystalline
      graphite (NCG) films, which are currently under intensive investigation due to
      their exceptional electronic properties, particularly fine electron emission
      characteristics. Deposited NCG films have demonstrated remarkable electron field
      emission properties having current density of up to 10 A/cm2. The films have also
      possessed good adhesion to silicon substrate. Carbon films and nucleation layer
      were characterized by scanning electron microscopy, transmission electron
      microscopy and Raman spectroscopy.

PMID- 22400281
TI  - Microstructure and biocompatibility of titanium oxides produced on nitrided
      surface layer under glow discharge conditions.
AB  - The disadvantages of titanium implants are their low wear resistance and the
      release of titanium elements into surrounding tissue. These can be eliminated by
      modifying the surface by surface engineering methods, among them nitriding under
      glow discharge conditions which allow to produce diffusive surface layers. Their
      combining with an oxide layer might be valuable for biological events occurring
      at the bone implant interface. The aim of this study was to enhance the titanium
      biomaterial performance via combining nitriding and oxidizing treatments in one
      process under glow discharge conditions. The oxynitrided surface layers were
      produced at 680 degrees C. The obtained layer was TiO + TiN + Ti2N + alphaTi(N)
      type and about 4-microm thick and was of diffusive character. This layer
      significantly increased wear resistance and slightly corrosion resistance
      compared to that of the reference titanium alloy. The produced titanium oxide was
      about 400-nm thick and built from fine crystallites. This oxide exhibits
      bioactivity in SBF (simulated body fluid). Osteoblasts of Saos-2 line incubated
      on this surface exhibited good adhesion and proliferation and ALP release
      comparable with cells cultured on the reference titanium alloy and TiN + Ti2N +
      alphaTi(N) surface layers. A quantitative analysis of blood platelets adhering to
      this layer revealed their highest amount in comparison to that on both the
      nitrided surface layer and titanium alloy. The presented study provided a simple
      and reproducible method of combining oxidizing and nitriding under glow discharge
      in one process. Experimental data in vitro suggests that titanium alloy
      oxynitriding under low temperatures at glow discharge conditions improves
      titanium alloy properties and biocompatibility and tissue healing. Therefore, the
      layer of TiO + TiN +Ti2N + alphaTi(N) type could be valuable for long-term bone
      implants.

PMID- 22400282
TI  - Technological and material related challenges for large area, high aspect-ratio,
      near teradot/inch2 areal density and three-dimensional structuring of
      polyaniline.
AB  - In this manuscript we report on a newly developed technology for the nanoscale
      processing of the conducting polyaniline (PANI) with an unprecedented areal
      patterning order and density control exceeding 0.25 teradot/inch2. High
      resolution electron beam lithography was used to generate ordered 2D and 3D
      templates. A novel type of resist and dose-modulated 3D-electron beam lithography
      (RDM-3D-EBL), extensively exploiting the intrinsic properties of resist-electron
      beam interaction is detailed. Surface initiated and template confined aniline
      polymerization, through catalytic activity of metallic platinum, was then
      exploited to provide a genuine method for controlled nanoscale processing of
      polyaniline, a prototypical conjugated polymer that definitively settled the
      concept of synthetic metals. Using nanoscale polymerization reactors, ultimate
      resolution patterning and processing control of single polyaniline nanostructures
      was feasible. Aspects of the nanoscale polyaniline growth mechanism are discussed
      and the highly controllable, sub-picogram scale fabrication is emphasized. Near
      teradot/inch2 pattern transfer technology, complex 3D structuring and physico
      chemical functionalization of polyaniline can be subsequently harnessed to build
      a large variety of architectures with potential for emerging optoelectronic
      technologies. The method is scalable, can be applied on virtually any type of
      flexible or rigid substrates and provides a generic approach for nanopatterning
      surfaces with functional polymers. Technological and material related fabrication
      challenges are detailed and discussed.

PMID- 22400283
TI  - Simple mathematical models of high energy ion beam assisted deposition
      concentration profiles in binary thin films.
AB  - Mathematical models of composed high energy ion beam assisted deposition (IBAD)
      concentration profiles of implanted component in binary thin films are described.
      Yields of the backscattered ions and sputtering of the deposited component are
      considered. A Gaussian probability density is assumed to apply to the ion range
      distribution. The construction of concentration profiles of various shapes is
      considered. These profiles should of course be constructed based on continuous
      changes of the process parameters, but certain technical problems can arise with
      this continuous parameter changes. Therefore, it has been assumed that the
      changes to the process parameters are discrete and proceed in several steps. The
      resulting mathematical models are combinations of error functions. Mathematical
      models can be used as regression functions for the determination of some
      parameters, e.g., the sputtering yield. Based on the mathematical model the
      gradient concentration profile of nitrogen in the SiNx film was experimentally
      produced by the IBAD method, measured by Rutherford backscattering spectroscopy
      and compared with the mathematical model.

PMID- 22400284
TI  - Temperature dependence of the giant magnetoresistance in Fe/DNA/Fe structure.
AB  - A numerical study is presented to investigate the spin-dependent transport
      through poly(dG)-poly(dC) DNA molecule sandwiched between ferromagnetic contacts
      in the absence and in the presence of environmental effects. Making use of tight
      binding procedure and within the framework of a generalized Green's function
      technique, the room temperature current-voltage characteristics of DNA molecule
      and the giant magnetoresistance (GMR) of Electrode/DNA/Electrode structure, with
      iron (Fe) as the electrode are studied. It is found that the GMR to be lower than
      12% for small applied bias and about 35% for applied bias larger than 2.5 volts.
      Considering the environmental effects, the GMR would be increased up to 13% at a
      bias lower than 2 volts and decreases up to 23% for the bias about 2.5 volts. In
      addition, our calculations indicate that for applied biases around 2.5 volts, the
      GMR decreases when the temperature increased.

PMID- 22400285
TI  - Shear-enhanced solution precipitation: a simple process to produce short
      polymeric nanofibers.
AB  - The growing interest in polymeric nanofibers has been increasing the push for the
      development of simple and efficient nanofiber-preparation techniques. We herein
      describe how a conventional solution process is readapted to suit the needs for
      fast and efficient production of short polymeric nanofibers. Poly(ethylene-co
      acrylic acid) (PEAA), a semi-crystalline polymer, was used as model. When a PEAA
      solution was injected into an alcoholic non-solvent while simultaneously applying
      high shear to the non-solvent system, PEAA nanofibers were obtained with average
      diameter as thin as 113 nm and length as short as 4.5 microm. The fiber diameter
      and length were also adjustable by varying the operating parameters. This one
      step technique advances the currently available nanofabrication tools by
      adjusting a widely accepted concept to the nano-scale. It may constitute a viable
      method for large-scale production of short polymeric nanofibers. KEYWORDS:
      Polymer Nanofibers, Solution Dispersion, Shear-Enhanced Precipitation,
      Poly(ethylene-co-acrylic acid), Operating Parameters, Short Nanofibers.

PMID- 22400286
TI  - Self-rewetting fluids with suspended carbon nanostructures.
AB  - Thermal management is very important in modern electronic systems. Recent
      researches have been dedicated to the study of the heat transfer performances of
      binary or multi-component heat transfer fluids with peculiar surface tension
      properties and in particular to "self-rewetting fluids," i.e., liquids with a
      surface tension increasing with temperature and concentration. Thermophysical
      properties like surface tension, wettability and thermal conductivity, at
      different temperatures, have been measured not only for binary mixtures, but also
      for a number of ternary aqueous solutions with relatively low freezing point and
      for nanoparticles suspensions (so called nanofluids). Some of them interestingly
      exhibit the same anomalous positive surface tension gradient with temperature as
      binary self-rewetting solutions. Since in the course of liquid/vapour phase
      change, self-rewetting fluids behaviour induces a rather strong liquid inflow
      (caused by both temperature and concentration gradients) from the cold region
      (where liquid condensates) to the hot evaporator region, several interesting
      applications may be envisaged, e.g., the development of advanced wickless heat
      pipes for utilization in reduced gravity environments. The present work is
      dedicated to the study of the thermophysical properties of nanofluids based on
      water/alcohol solutions with suspended carbon nanostructures, in particular
      single-wall carbon nanohorns (SWNH), synthesised by an homemade apparatus with an
      AC arc discharge in open air. The potential interest of the proposed studies
      stems from the large number of possible industrial applications, including space
      technologies and terrestrial applications, such as cooling of electronic
      components.

PMID- 22400287
TI  - Oxidation behaviour of Ti2AIN films composed mainly of nanolaminated MAX phase.
AB  - In this paper, we reported the oxidation behaviour of Ti2AIN films on
      polycrystalline Al2O3 substrates. The Ti2AIN films composed mainly of
      nanolaminated MAX phase was obtained by first depositing Ti-Al-N films using
      reactive sputtering of two elemental Ti and Al targets in Ar/N2 atmosphere and
      subsequent vacuum annealing at 800 degrees C for 1 h. The Ti2AIN films exhibited
      excellent oxidation resistance and thermal stability at 600-900 degrees C in air.
      Very low mass gain was observed. At low temperature (600 degrees C), no oxide
      crystals were observed on film surface. Blade-like Theta-Al2O3 fine crystals
      formed on film surfaces at 700-800 degrees C. At high temperature (900 degrees
      C), firstly Theta-Al2O3 formed on film surface and then transformed into alpha
      Al2O3. At 700-900 degrees C, a continuous Al2O3 layer formed on Ti2AIN films
      surface, acting as diffusion barrier preventing further oxidation attack. The
      mechanism of the excellent oxidation resistance of Ti2AIN films was discussed
      based on the experimental results.

PMID- 22400288
TI  - An effect of silicon micro-nano-patterning arrays on superhydrophobic surface.
AB  - Superhydrophobic surface can be fabricated by creating a rough surface at very
      fine scale and modify it with low-surface energy material. To obtain the optimum
      superhydrophobicity, the surface roughness must be maximized. To avoid the
      limitation of scaling down the pattern size by using an expensive lithography
      tools, the surface roughness factor (r) was increased by means of changing an
      asperity shape so as to increase its overall surface area. In this paper, the
      patterns of the asperities under studied were wave stripes, line stripes,
      cylindrical pillars, square pillars, pentagonal pillars, hexagonal pillars, and
      octagonal pillars. All pillar shapes were arranged in square arrays, hexagonal
      arrays, and continuous stripes. The asperities sizes and the pitches were varied
      from 1 to 5 microm with 10 microm of asperity height. Then the patterned surfaces
      were coated with polydimethylsiloxane mixed with 10 wt% dicumylperoxide. It was
      found that the stripe asperities can generate only hydrophobic surface with water
      contact angle (WCA) of 135 degrees to 145 degrees. The pillars with square and
      hexagonal arrays had the WCA of 149 degrees to 158 degrees. The pentagonal
      pillars with square and hexagonal arrays achieved the highest WCA with an average
      WCA of 156 degrees. It was evident that the pillar shape had significant effect
      on the superhydrophobicity.

PMID- 22400289
TI  - Hydrothermal synthesis and electrochromic properties of potassium tungsten oxide
      nanorods.
AB  - Hexagonal K2W4O13 nanorods have been synthesized by hydrothermal treatment of the
      WO3 x H2O precipitate at 180 degrees C in the presence of K2SO4. The K2W4O13
      nanorod single crystals of approximately 12 nm in diameter and tens to few
      hundreds nm long with the principal axis along the (001) direction were obtained
      when hydrothermal treatment was conducted in the presence of sufficient amount of
      K2SO4 while shorter nanorods with the same preferred orientation were obtained
      when less amount of K2SO4 was employed. On the other hand, square platelets of
      approximately 100 nm wide were obtained when prepared in the absence of the
      K2SO4. The important role of K2SO4 on morphological control of the hydrothermal
      products was explained based on selective adsorption of the sulfate ions on the
      crystal planes parallel to the (001) direction retarding the growth of these
      faces. The nanorod film showed satisfactory electrochromic property and can be
      used as a promising material in electrochromic application.

PMID- 22400291
TI  - Nanocrystalline Pd alloy films coated by electroless deposition.
AB  - The structures of palladium and palladium alloys thin films deposited from
      organic electrolytes onto metallic substrates by electroless plating method have
      been investigated. The coatings are dense, pore-free 0.005-1 microm thick films
      with high adhesive strength to the substrate surface. EDX, XRD, SEM and TEM
      methods were used to determine the composition and structure of alloy coatings of
      the following binary systems: Pd-Au, Pd-Ag, Pd-Ni, Pd-Pb, and ternary system Pd
      Au-Ni. The coatings of Pd-Au, Pd-Ag and Pd-Ni have a solid solution structure,
      whereas Pd-Pb is intermetallic compound. It has been found that the deposited
      films consist of nanocrystalline grains with sizes in the range of 11-35 nm.
      Scanning and transmission electron microscopy investigations reveal the existence
      of clusters formed by nanocrystalline grains. The origin for the formation of
      nanocrystalline structures of coating films is discussed.

PMID- 22400290
TI  - Photocatalytic activity and UV-protection of TiO2 nanocoatings on poly(lactic
      acid) fibres deposited by pulsed magnetron sputtering.
AB  - The application of nanocoatings in the textile finishing is increasingly being
      explored because they open a whole new vista of value-addition possibilities in
      the textile sector. In the present work, low temperature pulsed DC magnetron
      sputtering method was used to create functional TiO2 nanocoatings on poly(lactic
      acid) textile fibres surfaces. In this study, the principal objectives in the
      application of TiO2 nanocoatings to textile materials are to impart UV protection
      functions and self-cleaning properties to the textile substrates. The TiO2 films
      were characterized by X-ray diffraction, scanning electron microscopy, atomic
      force microscopy, transmission electron microscopy, UV-visible spectroscopy and
      contact angle analysis. The Photocatalytic activity of the films was tested by
      measuring the photodegradation rates of rhodamine-B dye aqueous solution under UV
      light irradiation. The ultraviolet protection function was tested according to
      the Australian/New Zealand standards. It was observed that the TiO2 nanocoatings
      on poly(lactic acid) fibres showed an excellent ultraviolet protection (> 40)
      function and the photocatalytic efficiency was maintained even after a strong
      washing treatment.

PMID- 22400292
TI  - Tantalum-based thin film coatings for wear resistant arthroprostheses.
AB  - Cobalt-chromium-molybdenum alloys with high carbon content (HC-CoCrMo) are widely
      used as materials for arthroprosthesis, in particular in metal-on-metal (MoM) hip
      joints. In spite of their good wear and corrosion resistance, production of
      metallic wear particles and metal ion release will occur on a large time-scale.
      An enhancement of the metal ion level in the patient's blood and urine is often
      reported in clinical data. Hypersensitivity, inflammatory response and cell
      necrosis can occur as consequence. So implants on young patients and women on
      childbearing age are not so widespread. The aim of this research is the
      realization of a thin film coating in order to improve the biocompatibility of Co
      based alloys and to reduce debris production, ion release and citotoxicity. The
      innovative process consists of a thermal treatment in molten salts, in order to
      obtain a tantalum enriched thin film coating. Tantalum is chosen because it is
      considered a biocompatible metal with high corrosion resistance and low ion
      release. Three HC-CoCrMo alloys, produced by different manufacturing processes,
      are tested as substrates. The coating is a thin film of TaC or it can be composed
      by a multilayer of two tantalum carbides and metallic tantalum, depending on the
      temperature of the treatment and on the carbon content of the substrate. The thin
      films as well the substrates are characterized from the structural, chemical and
      morphological point of view. Moreover mechanical behaviour of treated and
      untreated materials is analyzed by means of nanohardness, scratch and ball-on
      disc wear tests. The coating increases the mechanical and tribological properties
      of HC-CoCrMo.

PMID- 22400293
TI  - Fine structure and related properties of the assembleable carbon nanotubes based
      electrode for new family of biosensors with chooseable selectivity.
AB  - Surfaces of constituent parts of biosensors based on single wall carbon nanotube
      layer were investigated and compare for properly functioning and faulty
      biosensors. Though the original technology is acceptable for changing of the
      selectivity, only glucose sensitive biosensors are investigated. Based on the
      results of the study, a correlation between the features of the nanoscale
      structures and parameters of amperiometric biosensors for assemblage of which an
      innovative approach is described. Original template of the electrodes has been
      prepared on a base of single wall carbon nanotube layer deposited on the
      supporting polycarbonate membrane. Original immobilisation of enzymes within
      special membrane allows functional modification of biosensors being accomplished
      by simple replacement of the enzymatic membrane. The original technology leads to
      a novel family of biosensors acceptable for detection of wide range of
      carbohydrates. The morphology and the local electric properties of the
      constituent parts of the biosensors are characterized by scanning probe
      microscopy. The sensitivity, selectivity and stability are described for typical
      types of the biosensors.

PMID- 22400294
TI  - Porous silicon-based direct hydrogen sulphide fuel cells.
AB  - In this paper, the use of Au/porous silicon/Silicon Schottky type structure, as a
      direct hydrogen sulphide fuel cell is demonstrated. The porous silicon filled
      with hydrochlorid acid was developed as a proton conduction membrane. The
      Au/Porous Silicon/Silicon cells were fabricated by first creating the porous
      silicon layer in single-crystalline Si using the anodic etching under
      illumination and then deposition Au catalyst layer onto the porous silicon. Using
      80 mM H2S solution as fuel the open circuit voltage of 0.4 V was obtained and
      maximum power density of 30 W/m2 at room temperature was achieved. These results
      demonstrate that the Au/Porous Silicon/Silicon direct hydrogen sulphide fuel cell
      which uses H2S:dH2O solution as fuel and operates at room temperature can be
      considered as the most promising type of low cost fuel cell for small power
      supply units.

PMID- 22400295
TI  - An electrochemical impedance spectroscopy study of polymer electrolyte membrane
      fuel cells electrocatalyst single wall carbon nanohorns-supported.
AB  - Electrochemical impedance spectroscopy (EIS) was used to study the polymer
      electrolyte membrane fuel cells (PEMFC) performance when using single wall carbon
      nanohorns (SWNH) to support Pt nanoparticles. Additionally, as-prepared and
      oxidized SWNH Pt-supports were compared with conventional carbon black. Two
      different oxidizing treatments were considered: oxygen flow at 500 degrees C and
      reflux in an acid solution at 85 degrees C. Both oxidizing treatments increased
      SWNH surface area; oxygen treatment increased surface area 4 times while acid
      treatment increased 2.6 times. The increase in surface area should be related to
      the opening access to the inner tube of SWNH. Acid treatment of SWNH increased
      chemical fragility and decreased electrocatalyst load in comparison with as
      prepared SWNH. On the other hand, the oxygen treated SWNH sample allowed to
      obtain the highest electrocatalyst load. The use of as-prepared and oxygen
      treated SWNH showed in both cases catalytic activities 60% higher than using
      conventional carbon black as electrocatalyst support in PEMFC. Moreover, EIS
      analysis indicated that the major improvement in performance is related to the
      cathode kinetics in the as-prepared SWNH sample, while concerning the oxidized
      SWNH sample, the improvements are related to the electrokinetics in both anode
      and cathode electrodes. These improvements should be related with differences in
      the hydrophobic character between SWNH and carbon black.

PMID- 22400296
TI  - Epoxy composite with milimetric carbon nanotubes.
AB  - Composite of multi-walled carbon nanotubes (MWCNT) and epoxy resin DGEBA were
      obtained with DDM hardener. The MWCNT were synthesized with length of millimeters
      by camphor/ferrocene pyrolysis. Different cure temperatures of DGEBA/DDM with
      addition of up to 1% MWCNT were studied to evaluate eventual changes in cure
      kinetics by differential scanning calorimetry (DSC). No change was detected in
      glass transition temperature with insertion of MWCNT although the cure enthalpy
      has been reduced.

PMID- 22400297
TI  - Computation of detour index of TUHC6[2p, q] nanotubes for any p and q.
AB  - The detour d(i, j) between vertices i and j of a graph is the number of edges of
      the longest path connecting these vertices. The matrix whose (i, j)-entry is the
      detour between vertices i and j is called the detour matrix. The half sum D of
      detours between all pairs of vertices (in a connected graph) is the detour index,
      i.e., D = (1/2) Sigma(j) Sigma(i) d(i, j). In this paper, we computed the detour
      index of TUHC6[2p, q] nanotubes for any p and q.

PMID- 22400298
TI  - Detailed characterization of hydrothermally synthesized SnO2 nanoparticles.
AB  - 3-4 nm of SnO2 nanoparticles having uniform spherical shape were successfully
      synthesized using a hydrothermal method. The hydrothermal method has many
      advantages over other methods of preparing nanoparticles (such as sol-gel, solid
      state, and chemical precipitation), because there is no need for calcination and
      milling steps. The particles were characterized by X-ray diffraction, pore size
      diamater analysis, transmission electron microscope, scanning electron microscope
      analysis, Raman spectroscopy, and thermogravimetric analysis/differential
      thermogravimetric analysis. The results confirm that SnO2 nano powders are
      homogeneous, nano scale, and of high crystalline quality.

PMID- 22400299
TI  - Reactive pulsed-DC sputtered Nb-doped VO2 coatings for smart thermochromic
      windows with active solar control.
AB  - Thermochromic VO2 thin films have successfully been grown on SiO2-coated float
      glass by reactive pulsed-DC magnetron sputtering. Different Nb doping amounts
      were introduced in the VO2 solid solution during the film growing which resulted
      in films with distinct semiconducting-metal phase transition temperatures. Pure
      VO2 showed improved thermochromic behavior as compared with VO2 films prepared by
      conventional DC sputtering. The transition temperatures were linearly decreased
      from 59 down to 34 degrees C with the increase in Nb content. However, the
      luminous transmittance and the infrared modulation efficiency were markedly
      affected. The surface morphology of the films was examined by scanning electron
      microscopy (SEM) and showed a tendency for grain sized reduction due to Nb
      addition. Moreover, the films were found to be very dense with no columnar
      microstructure. Structural analyses carried out by X-ray diffractometry (XRD)
      revealed that Nb introduces significant amount of defects in the crystal lattice
      which clearly degrade the optical properties.

PMID- 22400300
TI  - Application of alkali metal-doped carbons for hydrogen recovery and isotope
      separation.
AB  - Hydrogen-sorption isotherms of alkali metal-doped carbons at 77 K were determined
      for promoting application of these materials as hydrogen-recovery and isotope
      separation agent. The hydrogen-sorption behavior of rubidium-doped Grafoil, with
      composition of RbC24, showed high sorption ability against hydrogen at low
      pressure. Taking into account the fact that sorption-desorption was fast and
      reversible, and the equilibrium pressure at half coverage was very low, i.e., 40
      Pa, RbC24 prepared from Grafoil is promising as a recovery agent for hydrogen gas
      at low pressure. The hydrogen (H2)/deuterium(D2)-sorption isotherms of potassium
      doped carbons with composition of KC10, prepared from multi wall carbon nanotube
      (MWCNT) and carbons derived from petroleum cokes with heat-treatment temperatures
      of 1000 and 1500 degrees C, were also determined. Isotope separation coefficient
      was estimated from those isotherms. A very large isotope effect was found for
      KC10 prepared from MWCNT, comparable to those prepared from carbons with heat
      treatment temperatures of 1000 or 1500 degrees C. However, a severe problem was
      found for KC10 (MWCNT) that repetition of the sorption-desorption cycles resulted
      in the decrease of the sorbed amount of H2 and D2.

PMID- 22400301
TI  - Spectroscopic investigations on epoxy--multiwall carbon nanotubes composites.
AB  - Room temperature electron spin resonance spectra of epoxy resins loaded with
      various concentrations of multiwalled carbon nanotubes of various lengths are
      analyzed. The resonance spectrum near the free electron line position is
      dominated by a single almost symmetric line assigned to delocalized electrons
      residing on multiwalled carbon nanotubes. The experimental research shown that:
      (1) The dependence of the g-factor on nanotubes length is controlled by the
      distortions of multiwalled carbon nanotubes. (2) The dependence of the g-factor
      on the concentration of multi-walled nanotubes reflects the interactions between
      electrons localized on different nanotubes. In insulating composites, the
      resonance line width broadens as the length and the concentration of multiwalled
      carbon nanotubes is increased. (3) For conducting composites, the dependence of
      the electron spin resonance line width on the length and concentration of
      multiwalled carbon nanotubes is controlled by Elliott contribution and exchange
      interactions, respectively. (4) The concentration of conduction electrons
      increases as the length and the concentration of multiwalled carbon nanotubes are
      increased.

PMID- 22400302
TI  - Characterization of Si3N4/TiO2 nanocomposite coatings prepared via micro arc
      oxidation.
AB  - Nanocomposite Si3N4/TiO2 coatings were prepared by micro arc oxidation with Si3N4
      nanoparticles in solution and the effects of time and current density on the
      coatings formation and growth were studied. X-ray diffraction analysis was
      utilized to detect the nanocrystalline and amorphous characteristics of the
      composite coatings. Surface morphology and nanostructure of coatings were
      observed by scanning electron microscopy and atomic force microscopy. The results
      showed that current density had great effects on phase transformation of Si3N4
      nanoparticles in composite coatings. The moderate current density conduced to
      homogeneous distribution of silicon nitride nanoparticles in the coatings.
      Moreover, fine nanoparticles that entered and homogeneously distributed in the
      composite coating led to an increase in the barriers for nucleation of oxide
      based grains and inhibition of grain growth. Therefore, the introduction of
      nanoparticles resulted in the formation of smaller oxide-based grains.

PMID- 22400303
TI  - Ti-WC nanocrystalline coating formed by surface mechanical attrition treatment
      process on 316L stainless steel.
AB  - Nanocrystalline coatings were performed on the surface of 316L stainless steel
      plates mechanically with a mixture of Ti and WC powders under vacuum conditions.
      The targets were replaced in the end of the high energy milling rig, while Ti-WC
      mixture was milled as usual. It is shown that the coatings are nanocrystalline in
      nature with narrow distribution of average size of nanocrystallites. X-ray
      diffraction and scanning electron microscopy (with energy-dispersive
      spectrometer) revealed that the top layer of the coatings is uniform.
      Microhardness, roughness and primary corrosion tests (tafel tests) proved
      enhancement of coated samples with respect to raw materials. Transmission
      electron microscope image of deformed surface confirmed surrounding of
      nanoparticles by dislocation loops after plastic deformation.

PMID- 22400304
TI  - Preparation of silicon nanoparticular nanocomposite with thin interparticular tin
      matrix.
AB  - Technology of a composite material of silicon nano-particles (99.999 w% for
      semiconductors) arranged densely in a metal tin matrix (99.7 w%) is presented in
      the present paper. The main motivation for the technology development is an
      endeavor to prepare a nano-composite material in which semiconductor particles
      are crowded densely by applying high pressure in a metal matrix. In the above
      arrangement, a coexistence of very narrow mesh nanostructure of a tin matrix with
      dispersed nanoparicles of silicon is involved. With the high level of volume
      density of nanoparticles, the surface interface between metal and semiconductor
      attains an extraordinarily large size. Thanks to this fact, a significant
      enhancement of the volume rate of the transitional Shottky's zone between metal
      tin and semiconductive silicon has been reached. Based on preliminary
      measurements, the abovementioned structure is characterized by an active
      influence on material behavior in the area of temperature dependence of
      resistivity which cannot be explained by mere superposition of parallel currents
      in two independent components: silicon and tin.

PMID- 22400305
TI  - The effect of diamond nanoparticles on redox and immune parameters in rats.
AB  - The objective of the study was to evaluate the effect of nanodiamond (ND)
      particles manufactured by detonation method (size of grains 2-10 nm) on organism
      health status. Wistar rats were administrated with diamond nanoparticles colloid
      by intravenous and intraperitoneal injection. Both routes of administration
      increased superoxide dismutase (SOD) activity and at the same time decreased
      activity of glutathione reductase (GR) and glutathione peroxidase (GPx) within
      erythrocytes. ND did not significantly affect neither total antioxidative state
      (TAS) nor thiobarbituric acid reactive substances (TBARS) in examined animals
      blood plasma. This study was also designed to examine the effect of ND on the
      phagocytosis activity and oxidative burst of innate immune cells. Both
      intravenous and intraperitoneal administration of ND hydrocolloid decreased the
      number of the phagocytosing neutrophiles stimulated by E. coli. Independently of
      the injection method nanodiamond increased the number of cells with stimulated
      oxidative burst and it suppressed the mechanism of oxygen dependent bacteria
      elimination.

PMID- 22400306
TI  - Electronic structure and magnetic properties of a molecular octanuclear chromium
      based ring.
AB  - A comprehensive study of electronic and magnetic properties of Cr8F8Piv16 (HPiv =
      pivalic acid, trimethyl acetic acid) molecular ring is presented. The total,
      local and orbital projected density of states are calculated by the first
      principle density functional theory calculations using the package SIESTA. The
      original molecule has been approximated by replacing the pivallic groups by H
      atoms (hydrogen saturation). Electron density, deformation density, electrostatic
      potential and spin density maps are analyzed and compared with experiment for the
      first time. Magnetic properties are investigated in detail. Magnetic moments are
      calculated using two different approaches: the Mulliken one and integration of
      muffin-tin sphere with a given radius. Different magnetic configurations
      (ferromagnetic, antiferromagnetic and many more with randomly distributed spins
      up and down) are considered to extract exchange interaction parameter J and check
      the stability of its estimate.

PMID- 22400307
TI  - Nano-cones formation on a surface of Ge, Si crystals and Si1-xGe(x) solid
      solution by laser radiation.
AB  - The study of self-assembling nano-cones induced by irradiation of nanosecond
      Nd:YAG laser pulses on a surface of a Si1-xGe(x) solid solution is reported. It
      is shown that dynamics of nano-cones formation depends on concentration of Ge
      atoms (x) in Si lattice and on the intensity of laser radiation. Two different
      processes of nano-cones formation depending on x are observed. The first one-at
      higher concentration of Ge atoms x = 0.3-0.4 and the second one-at lower
      concentration of Ge atoms at x = 0.15 take place. At the first stage, similar
      processes of nano-cones formation occur. It means, at low intensity of laser
      radiation 1 < 2.0 MW/cm2 Ge atoms drift to the irradiated surface due to Thermo
      gradient effect and Ge-rich phase is formed for both concentration ranges. The
      second stage is different for low and high Ge content ranges. At the higher
      concentration of Ge atoms and intensity of laser radiation 1 > 2.0 MW/cm2 nano
      cones formation takes place by Stransky-Krastanov mode. On the same time, at
      lower concentration of Ge atoms cones look like "tree ring" growth due to melting
      of Ge separated islands on the irradiated surface at intensity of laser radiation
      1 = 20 MW/cm2.

PMID- 22400308
TI  - Photocatalytic degradation of methylorange Using TiO2, WO3 and mixed thin films
      under controlled pH and H2O2.
AB  - Wastewaters resulting from textile industry sector have a different chemistry
      compared with most of the other wastewaters. The different dyes in excess are
      usually very stable and even small quantities can have a major impact to the
      effluent. In order to treat these wastewaters, photodegradation is a largely
      investigated process that can be up-scaled. Photocatalysts based on wide band gap
      semiconductors can be used in heterogeneous photocatalysis and mostly reported
      are TiO2 and WO3. Under UV irradiation they form electron-hole pairs that produce
      active species that can oxidize the dye molecules. The electron-hole
      recombination represents the main cause for low efficiencies and is limited by
      the use of oxidant systems like H2O2. Doctor blade technique, a reproducible, up
      scalable and low cost technique was used to obtain thin films. The reference dye,
      used in this experiment is methylorange in solution of 0.0125 mM, corresponding
      to average polluted water. In order to reduce the recombination in the catalysts,
      H2O2 is used. Another important aspect of the dye photocatalysis process,
      investigated in the paper is the adsorption of the dye molecule on the
      photocatalyst surface, strongly depending on pH which affects the dye's structure
      and the surface charge. Experiments are conducted at fixed pH values: 3, and
      respectively 7 covering values below and over the ZPC of the photocatalysts. The
      results show that TiO2/WO3 films have higher efficiency then the TiO2 and WO3
      films, mainly due to the surface morphology of the films. By adding H2O2, higher
      efficiencies are obtained, confirming that the electron-hole pair recombination
      is reduced. From the point of view of pH, higher efficiencies are obtained in
      acidic solutions and the results are comparatively discussed considering the
      dye's ionic/neutral structure and the photocatalyst surface charge. The
      efficiency was calculated using UV-VIS spectrophotometer measurements of the
      solution and the thin films were characterized by AFM and XRD.

PMID- 22400309
TI  - Detection of human papilloma viruses using nanostructurated silicon support in
      microarray technology.
AB  - In a typical microarray experiment, DNA is arrayed on a solid substrate as spots,
      the array being probed with a sample or a capture molecule of interest and the
      interaction monitored through different detection methods. The present study
      evaluates the possibility to use micro-array technology to genotype samples with
      Human Papilloma Viruses (HPV). The performance of DNA microarrays strongly depend
      on their surface properties. The efficiency of DNA immobilization in terms of
      sensitivity and specificity is one of the most important step in obtaining a
      microarray chip for diagnosis of HPV family viruses. Here we report the
      preparation and evaluation of nano-porous silicon surfaces for HPV detection
      based on DNA micro-array technique. Two different surfaces based on similar
      porous structure chemically modified in order to efficiently immobilize ss-DNA
      specific for HPV viruses were investigate.

PMID- 22400310
TI  - The electrical properties of epoxy resin composites filled with Cnts and carbon
      black.
AB  - This work introduces an experimental activity related to the realization of an
      epossidic nanostructured material that develops the function of covering for
      electronic circuits in aeronautical field. This covering meets the demand of
      protection of these circuits from possible troubles of electromagnetic nature. In
      order to realize this covering we used an epoxy resin as matrix (Epon 828) loaded
      with conductive nanofillers or carbon nanotubes (Cnts). To check the efficiency
      of the coating we have considered the carbon black, filler widely used as a
      conductive covering for screenings. We have considered different percentages of
      the different fillers, precisely 0.1%, 0.25% and 0.5% wt (% valued in comparison
      to the weight of the resin). From every mixture 12 samples have been obtained
      (the size of every sample is 10 mm x 10 mm x 10 mm). Every sample has been
      subjected to electrical measurements, that have concerned the measurement of
      current intensity and resistance (so as to allow the evaluation of the
      enhancement of the conductivity), through the application of different values of
      voltage. The results have demonstrated that the epoxy matrix loaded with Cnts
      yields higher values of electrical conductivity than the same matrix loaded with
      carbon black.

PMID- 22400311
TI  - Ellipsometric and Rutherford Back scattering Spectrometry studies of SiO(X)N(Y)
      films elaborated by plasma-enhanced chemical vapour deposition technique.
AB  - Silicon oxynitride (SiO(X)N(Y)) thin films were deposited by plasma-enhanced
      chemical vapour deposition technique (PECVD) from silane (SiH4), nitrous oxide
      (N2O), ammonia (NH3) and nitrogen (N2) mixture. Spectroscopic ellipsometry (SE),
      in the range of wavelengths 450-900 nm, was used to define the film thickness and
      therefore the deposition rate, as well as the refractive index as a function of
      the N2O gaseous flow. While considering the (Si3N4, SiO2, H2 or void)
      heterogeneous mixture, Maxwell Garnett (MG) theory allows to fit the SE
      measurements and to define the volume fraction of the different phases. Finally,
      Rutherford Backscattering Spectrometry (RBS) results showed that x = O/Si ratio
      increases gradually with increasing the N2O flow, allowing the correlation of the
      SiO(X)N(Y) films main parameters.

PMID- 22400312
TI  - A combined In situ grazing incidence small angle X-ray scattering and grazing
      incidence X-ray diffraction study of the growth of Ge Islands on pit-patterned
      Si(001) substrates.
AB  - The growth of Ge islands on a pit-patterned Si(001) template is investigated in
      situ, combining grazing incidence diffraction, multiple wavelength anomalous
      diffraction, and small angle scattering. This allows monitoring in situ the
      detailed structural and morphological evolutions of the pits, of the wetting
      layer and of the nucleated islands on the pit-patterned Si(001) substrate. It is
      shown that after Si regrowth, the Si substrate displays {107} and {1 1 11}
      facets. During the very first stages of Ge growth, the preliminary facets of the
      Si substrate are energetically unfavourable, and the pit facets break up into a
      rather complex pattern of {10n} and {11m} facets with n > 7 and m > 11. At 5 and
      6 ML, intensity rods from {105} and {113}-type facets appear in the GISAXS images
      revealing the formation of pyramids and domes, respectively. The degree of
      ordering, the shape, strain and composition of the islands are characterized
      during the growth process to provide a detailed evolution of their structure and
      morphology.

PMID- 22400313
TI  - Monitoring photonic nanojets from microsphere arrays by femtosecond laser
      ablation of thin films.
AB  - By comparing finite-difference time-domain near field simulations and femtosecond
      laser ablation of thin films, we characterize in three dimensional-space photonic
      nanojets from microsphere arrays. We demonstrate periodic drilling of transparent
      films with thickness up to 100 nm (onto absorbing substrates) is feasible with 1
      microm diameter silica spheres. Working with larger polystyrene spheres, the
      apparent increase of the propagation length of the photonic nanojets makes
      possible to drill films as thick as 500 nm. Interestingly, the lateral width of
      the produced craters can be maintained below 400 nm evidencing the low divergence
      of the nanojets. For backside illumination of the arrays, the ablation features
      are located at the top of the microspheres. We reveal field enhancements in and
      out the spheres as well as laser energy confinement at the particle substrate
      interface. The wide variety of features observed in the experiments open routes
      to fabricating nanomaterials.

PMID- 22400314
TI  - Nanostructure and internal strain distribution in porous silicon.
AB  - Porous silicon (PS) layers with different degrees of porosity have been
      fabricated and their nanostructure has been investigated using complementary
      methods as FE-SEM (field emission scanning electron microscopy), SAXS (small
      angle X-ray scattering), and Raman spectroscopy. Correlation of these results
      with strain analyses is also required for envisaged applications in MEMS
      technology. Symmetrical and asymmetrical rocking curves obtained by high
      resolution X-ray diffraction completed with reciprocal space maps (RSMs) explain
      the features observed in Raman spectra: the PS film in-depth contains two layers
      bulk and highly strained superficial layer, between them being a graded strain
      layer.

PMID- 22400315
TI  - Role of many body shake-up in core-valence-valence electron emission from single
      wall carbon nanotubes.
AB  - Auger core-valence-valence transitions from single wall Carbon nanotubes are
      studied using a tight-binding calculational scheme with nearest neighbor overlap,
      hopping interactions, and a double-zeta basis set. The resulting Hamiltonian
      approximates the unperturbed pi and sigma bands of the nanomaterials coupled with
      the free electron states outside the solid and the core-hole. As a first step,
      the Fermi's golden rule is applied to determine the so called one-electron
      spectrum of emitted electrons from different tubes, in which either the
      neutralizing or the ejected electrons, in the initial state, lie within nearest
      neighboring atomic sites to the core-hole. Many-body corrections are effectively
      modeled using a broadening function, which accounts for dynamic screening effects
      involving the initial and final states. Particular attention is paid to the
      asymmetric component of the broadening function, responsible for the shake-up of
      pi electrons. Finally, the Cini-Sawatzky distortion function is used to describe
      the final state effect of the hole-hole interaction. A quantitative estimation of
      the interplay of shake-up processes is proposed by adjusting the asymmetric
      parameters of the broadening function to reproduce measurements of Auger
      electrons ejected from bundles of single wall Carbon nanotubes.

PMID- 22400317
TI  - Nanometer scale assessment of mechanical strain induced in silicon by a periodic
      line array.
AB  - Measuring stress and strain, induced by nanostructures, at the nanometer scale is
      still a challenge. In this work, we investigate the strain induced by sub
      micrometric periodic line arrays deposited on single crystal (001) Si substrate.
      We study the influence of the lines width and the spacing between the lines for
      two sets of samples: a silicon nitride lines array and a poly-silicon line array
      capped with a Si3N4 stressor layer. The periodic strain field in mono-crystalline
      silicon is investigated by High Resolution X-ray Diffraction which is very
      sensitive to local strain (< 10(-4)), has the required resolution, and is non
      destructive. X-ray reciprocal space maps (RSM) are measured on a 4 circles
      goniometer with a laboratory source. The line arrays induce a periodic strain
      field in silicon, which gives rise to distinct satellites in reciprocal space.
      The intensity envelope of these satellites is related to the strain field in one
      cell. In order to assess this strain field in silicon, mechanical modeling is
      necessary. Elastic calculations are performed with a Finite Element Modeling
      (FEM) code in order to extract the displacement field that is used for structure
      factor calculations within kinematical approximation. The calculated reciprocal
      space map is compared to the experimental results in order to validate the strain
      field. We show that for capped poly arrays, the diffracted intensity envelope is
      influenced by the spacing between the lines. This area is filled with silicon
      nitride which induces a noticeable change in displacement and strain field. While
      for bare stressor arrays the nitride line width is responsible of change in
      displacement field and thus on the RSM intensity envelope.

PMID- 22400316
TI  - InGaAs quantum dots grown by molecular beam epitaxy for light emission on Si
      substrates.
AB  - The aim of this study is to achieve homogeneous, high density and dislocation
      free InGaAs quantum dots grown by molecular beam epitaxy for light emission on
      silicon substrates. This work is part of a project which aims at overcoming the
      severe limitation suffered by silicon regarding its optoelectronic applications,
      especially efficient light emission device. For this study, one of the key points
      is to overcome the expected type II InGaAs/Si interface by inserting the InGaAs
      quantum dots inside a thin silicon quantum well in SiO2 fabricated on a SOI
      substrate. Confinement effects of the Si/SiO2 quantum well are expected to
      heighten the indirect silicon bandgap and then give rise to a type I interface
      with the InGaAs quantum dots. Band structure and optical properties are modeled
      within the tight binding approximation: direct energy bandgap is demonstrated in
      SiO2/Si/InAs/Si/SiO2 heterostructures for very thin Si layers and absorption
      coefficient is calculated. Thinned SOI substrates are successfully prepared using
      successive etching process resulting in a 2 nm-thick Si layer on top of silica.
      Another key point to get light emission from InGaAs quantum dots is to avoid any
      dislocations or defects in the quantum dots. We investigate the quantum dot size
      distribution, density and structural quality at different V/III beam equivalent
      pressure ratios, different growth temperatures and as a function of the amount of
      deposited material. This study was performed for InGaAs quantum dots grown on
      Si(001) substrates. The capping of InGaAs quantum dots by a silicon epilayer is
      performed in order to get efficient photoluminescence emission from quantum dots.
      Scanning transmission electronic microscopy images are used to study the
      structural quality of the quantum dots. Dislocation free In50Ga50As QDs are
      successfully obtained on a (001) silicon substrate. The analysis of QDs capped
      with silicon by Rutherford Backscattering Spectrometry in a channeling geometry
      is also presented.

PMID- 22400318
TI  - Defect mediated magnetic interaction and high Tc ferromagnetism in Co doped ZnO
      nanoparticles.
AB  - Structural, optical and magnetic studies have been carried out for the Co-doped
      ZnO nanoparticles (NPs). ZnO NPs are doped with 3% and 5% Co using ball milling
      and ferromagnetism (FM) is studied at room temperature and above. A high Curie
      temperature (Tc) has been observed from the Co doped ZnO NPs. X-ray diffraction
      and high resolution transmission electron microscopy analysis confirm the absence
      of metallic Co clusters or any other phase different from wurtzite-type ZnO. UV
      visible absorption and photoluminescence studies on the doped samples show change
      in band structure and oxygen vacancy defects, respectively. Micro-Raman studies
      of doped samples shows defect related additional strong bands at 547 and 574 cm(
      1) confirming the presence of oxygen vacancy defects in ZnO lattice. The field
      dependence of magnetization (M-H curve) measured at room temperature exhibits the
      clear M-H loop with saturation magnetization and coercive field of the order of 4
      6 emu/g and 260 G, respectively. Temperature dependence of magnetization
      measurement shows sharp ferromagnetic to paramagnetic transition with a high Tc =
      791 K for 3% Co doped ZnO NPs. Ferromagnetic ordering is interpreted in terms of
      overlapping of polarons mediated through oxygen vacancy defects based on the
      bound magnetic polaron (BMP) model. We show that the observed FM data fits well
      with the BMP model involving localised carriers and magnetic cations.

PMID- 22400319
TI  - Magnetic properties of the molecular nanomagnet Cr7Cd: single ion and exchange
      anisotropy effects.
AB  - In order to verify two microscopic models of the molecular nanomagnet Cr7Cd we
      analyze a number of thermodynamic quantities calculated for two sets of
      parameters. The first model, with only single ion anisotropy, was established on
      the basis of the thermodynamic properties (by fitting susceptibility and
      magnetization) whereas the second, with single ion and bond-dependent exchange
      anisotropies, was based on the inelastic neutron scattering and EPR spectra. The
      calculations are performed by means of non-perturbative, numerically exact
      quantum transfer matrix technique on large scale parallel computers. We
      demonstrate that the predictions of the models are consistent in the region of
      small magnetic fields which do not exceed 10 T and differ significantly in higher
      fields. Comparison with the experiment leads to a conclusion that better modeling
      of magnetic torque requires more complex microscopic model with single ion and
      bond-dependent exchange anisotropies.

PMID- 22400320
TI  - Thermal stability of metal-silicide nanocrystal nonvolatile memory with barrier
      engineered tunnel layers.
AB  - WSi2 nanocrystal nonvolatile memory devices were fabricated with a silicon oxide
      nitride-oxide (SiO2: 2 nm/Si3N4:2 nm/SiO2:3 nm) tunnel layer. WSi2 nanocrystals
      of 2.5 nm diameters and a density of 3.6 x 10(12) cm(-2) were formed using radio
      frequency magnetron sputtering and annealing processes. The WSi2 nanocrystal
      nonvolatile memory device exhibited strong thermal stability during
      writing/erasing operations at temperatures up to 125 degrees C. When the
      writing/erasing voltages were applied at +10 V/-10 V for 500 ms, the memory
      window of the initial approximately 2.6 V decreased by approximately 1.1 V at 25
      degrees C and 0.4 V at 125 degrees C after 10(4) sec, respectively. These results
      show that WSi2 nanocrystals with barrier-engineered tunnel layers are possible
      for application in nonvolatile memory devices.

PMID- 22400321
TI  - Ge growth on vicinal si(001) surfaces: island's shape and pair interaction versus
      miscut angle.
AB  - A complete description of Ge growth on vicinal Si(001) surfaces is provided. The
      distinctive mechanisms of the epitaxial growth process on vicinal surfaces are
      clarified from the very early stages of Ge deposition to the nucleation of 3D
      islands. By interpolating high-resolution scanning tunneling microscopy
      measurements with continuum elasticity modeling, we assess the dependence of
      island's shape and elastic interaction on the substrate misorientation. Our
      results confirm that vicinal surfaces offer an additional degree of control over
      the shape and symmetry of self-assembled nanostructures.

PMID- 22400322
TI  - Photoluminescence efficiency and size distribution of self assembled ge dots on
      porous TiO2.
AB  - For Ge nanodots approximately 20 nm in diameter grown by annealing a thin
      amorphous Ge layer deposited by molecular beam epitaxy on a mesoporous TiO2 layer
      on Si(001), photoluminescence (PL) was observed as a wide near-infrared band near
      800 meV. Using a tight binding theoretical model, the energy-dependent PL
      spectrum was transformed into a dependence on dot size. The average dot size
      determined the peak energy of the PL band and its shape depended on the size
      distribution, including bandgap enlargement due to quantum confinement. Combining
      the dot sample PL with an established dependence of emission efficiency on dot
      diameter, it was possible to derive a dot size distribution and compare it with
      results obtained independently from atomic force microscopy.

PMID- 22400323
TI  - Cathode-luminescence from extrinsic impurities in bundles of carbon nanotubes: a
      possible role.
AB  - Luminescence spectra obtained by electron bombardment of carbon nanotubes bundles
      show an UV signal centered at about 380 nm. We show that these transitions are
      extrinsic to nanotubes, in the sense that they are not linked to any carbon
      compound or structure, but are caused by the residual catalyst material used in
      the growth process. A possible role of such luminescence attributable to
      impurities is also discussed. In fact our luminescence measurements, in
      association with laser ablation inductively coupled plasma mass spectrometry (LA
      ICP-MS) and X-ray photoelectron spectroscopy (XPS), permit us to assign these
      spectral bands to Zn and Al oxides. Our conclusions, supported by data in
      literature, and the comparison with the quantitative results obtained by LA-ICP
      MS spectrometry (which detects ppm) allows us to define cathode-luminescence
      analysis as a good technique to control cleanness and purity of carbon nanotube
      samples.

PMID- 22400324
TI  - Photovoltaic response of carbon nanotube-silicon heterojunctions: effect of
      nanotube film thickness and number of walls.
AB  - We report on the multiwall carbon nanotube application as energy conversion
      material to fabricate thin film solar cells, with nanotubes acting as
      photogeneration sites as well as charge separators, collectors and carrier
      transporters. The device consists of a semitransparent thin film of nanotubes
      coating a n-type crystalline silicon substrate. Under illumination electron-hole
      (e-h) pairs, generated in the nanotubes and in the silicon substrate underneath,
      are split and charges are transported through the nanotubes (electrons) and the n
      Si (holes). We found that a suitable thickness of the nanotube thin film, high
      density of Schottky junctions between nanotubes and n-Si and lowest number of
      nanotube walls are all fundamental parameters to improve the device incident
      photon to electron conversion efficiency. Multiwall carbon nanotubes have been
      synthesized by chemical vapour deposition in an ultra high vacuum chamber by
      evaporating a given amount of iron at room temperature and then exposing the
      substrate kept at 800 degrees C at acetylene gas. The amount of deposited iron is
      found to directly affect the nanotube size distribution (inner and outer
      diameter) and therefore the number of walls of the nanotubes.

PMID- 22400325
TI  - On morphology and strain field of Ge/Si(001) Islands according to TEM phase
      imaging method.
AB  - The mechanism driving Germanium islands nucleation and self-assembly is an
      important effect for opto-electronic applications, still not fully understood. We
      demonstrate that the new transmission electron microscopy phase imaging method
      provides insights on the distribution of strain and composition fields in and
      around the islands on rather large areas. The method consists of retrieving the
      phase from a focus series of plane view images. The phase image is representative
      of morphology, composition and strain. The results show that whatever the islands
      size and shape is, a maximum compressive strain is obtained at the apex of the
      islands compensated by a maximum tensile strain in the substrate close to the
      islands perimeter. The maximum compressive strain is associated to a larger Ge
      concentration. The distribution of tensile strain varies with the shape of the
      islands: for square base pyramidal "hut" islands, a maximum tensile strain is
      obtained at the four corners of the pyramid base and for "dome" islands, the
      tensile strain is less pronounced and affects almost the whole island perimeter.
      These results are consistent with the higher strain relaxation level of "dome"
      islands in comparison to those of "hut" islands.

PMID- 22400326
TI  - Size dependent anisotropic strain and optical properties of strained Si
      nanocrystals.
AB  - We report on the growth of strained Si nanocrystals (NCs) of sizes in the range 5
      43 nm and analyze the detailed nature of strain and its influence on the optical
      properties of the NCs as a function of size. Freestanding Si NPs were prepared in
      a controlled way using a contamination free mechanical ball milling for duration
      2-40 hrs. Structural analysis based on X-ray diffraction (XRD) pattern and high
      resolution transmission electron microscopy (HRTEM) confirms the good crystalline
      nature of these Si NCs. A detailed analysis of XRD line profile reveals that
      nature of the strain is anisotropic and the screw type dislocations are the main
      contributors to the lattice strain. The dislocation density and corresponding
      strain changes non-monotonically, while the crystallite size changes
      monotonically with milling time. Direct evidence of dislocations is shown from
      HRTEM images. The UV-vis-NIR absorption spectra of the Si NCs show an enhanced
      absorption band in the visible region that shows a systematic blue shift with
      reduced NC sizes. Si NCs with size approximately 5-10 nm exhibits a distinct
      photoluminescence (PL) band in the visible region at 580-585 nm at room
      temperature, while higher size NCs does not exhibit any visible emission. PL
      excitation measurement shows a very small Stokes shift for the visible emission
      band indicating no involvement of defects/interface in the emission. We argue
      that the observed absorption and emission can be explained based on the enhanced
      confinement effect on the strained Si NCs due to the combined effect of strain
      and size quantization.

PMID- 22400327
TI  - Linearly polarized light emission from InGaN/GaN quantum well structure with high
      indium composition.
AB  - We fabricated yellow (575 nm) emitting a-plane InGaN/GaN light emitting diode
      (LED). Microstructure and stress relaxation of the InGaN well layer were observed
      from the images of dark field transmission electron microscopy. The LED chip was
      operated at 3.7 V, 20 mA, and the polarization-free characteristic in nonpolar
      InGaN layer was confirmed from a small blue-shift of approximaely 1.7 nm with
      increase of current density. The high photoluminescence (PL) efficiency of 30.4%
      showed that this non-polar InGaN layer has a potential of application to green
      red long wavelength light emitters. The PL polarization ratio at 290 K was 0.25
      and the energy difference between two subbands was estimated to be 40.2 meV. The
      low values of polarization and energy difference were due to the stress
      relaxation of InGaN well layer.

PMID- 22400328
TI  - Photocurrent generation in Ge nanocrystal/Si systems.
AB  - We report on the generation of photocurrent in the visible and ultraviolet range
      from planar devices built from the Ge nanocrystals grown on a heavy n-doped
      Si(001) substrate covered with 5 nm thick thermally grown SiO2. These Ge
      nanostructures/SiO2/n(+)-Si devices are shown to generate photocurrent with an
      Incident-Photon-to-electron Conversion Efficiency (IPCE) spectral range depending
      on the Ge nanocrystals size. The increase of the IPCE value of our devices in the
      350-600 nm range correlates well with the absorbance of Ge.

PMID- 22400330
TI  - New synthesis approach for hybrid Gd(III)-loaded Nanocrystalline TiO2 as
      potential magnetic resonance imaging contrast agents.
AB  - A new aqueous "in situ and one pot" method to elaborate surface-functionalized
      Gd(III)-doped anatase TiO2 nanoparticles, starting from
      heterometallic/heteroleptic Gd-Ti alkoxides, is reported. Full characterization
      and thermal behaviour of the nanomaterials demonstrate that this molecular
      approach offers the convenience of working under soft temperature and pH
      conditions in order to allow fine tuning of the organic surface functionalization
      and gadolinium doping. In vitro phantom images exhibit potential MRI T1-contrast
      agent properties.

PMID- 22400329
TI  - Synthesis of 3C-SiC nanocrystals at the SiO2/Si interface by CO2 thermal
      treatment.
AB  - We report 3C-SiC nano-crystals synthesis by thermal annealing of SiO2/Si wafers
      in CO2 gas. The nano-crystals have been characterized using scanning electron
      microscopy and atomic force microscopy. These results are correlated with
      selective area electron diffraction paterns, and transmission electron microscopy
      observations that evidence the formation of cubic SiC nano-crystals epitaxied on
      Si. In our experimental conditions, the crystals size is in the range 10-60 nm,
      increasing with the treatment time, as the crystals density. Using isotopic
      labelled SiO2 associated with Nuclear Reaction Analysis (NRA) and Nuclear Narrow
      Resonance Profiling (NRP), oxygen exchanges between CO2 and SiO2 could be
      evidenced.

PMID- 22400331
TI  - Role of roughness parameters on the tribology of randomly nano-textured silicon
      surface.
AB  - This experimental work is oriented to give a contribution to the knowledge of the
      relationship among surface roughness parameters and tribological properties of
      lubricated surfaces; it is well known that these surface properties are strictly
      related, but a complete comprehension of such correlations is still far to be
      reached. For this purpose, a mechanical polishing procedure was optimized in
      order to induce different, but well controlled, morphologies on Si(100) surfaces.
      The use of different abrasive papers and slurries enabled the formation of a wide
      spectrum of topographical irregularities (from the submicro- to the nano-scale)
      and a broad range of surface profiles. An AFM-based morphological and
      topographical campaign was carried out to characterize each silicon rough surface
      through a set of parameters. Samples were subsequently water lubricated and
      tribologically characterized through ball-on-disk tribometer measurements.
      Indeed, the wettability of each surface was investigated by measuring the water
      droplet contact angle, that revealed a hydrophilic character for all the
      surfaces, even if no clear correlation with roughness emerged. Nevertheless, this
      observation brings input to the purpose, as it allows to exclude that the
      differences in surface profile affect lubrication. So it is possible to link the
      dynamic friction coefficient of rough Si samples exclusively to the opportune set
      of surface roughness parameters that can exhaustively describe both height
      amplitude variations (Ra, Rdq) and profile periodicity (Rsk, Rku, Ic) that
      influence asperity-asperity interactions and hydrodynamic lift in different ways.
      For this main reason they cannot be treated separately, but with dependent
      approach through which it was possible to explain even counter intuitive results:
      the unexpected decreasing of friction coefficient with increasing Ra is
      justifiable by a more consistent increasing of kurtosis Rku.

PMID- 22400332
TI  - Temperature dependent photoluminescence properties of InAs/InP quantum dashes
      subjected to low energy phosphorous ion implantation and subsequent annealing.
AB  - We report on the impact of phosphorous ion-implantation-induced band gap tuning
      on the temperature dependent photoluminescence (PL) properties of InAs/InP
      quantum dashes (QDas). The high temperature range carriers' activation energy,
      extracted from Arrhenius plots, is found to decrease from 238 to 42 meV when the
      ion implantation dose increases from 10(11) cm(-2) to 5 x 10(14) cm(-2) which is
      consistent with the observed emission energy blueshift increase with increasing
      the ion implantation doses. This effect is attributed to the As/P exchange which
      reduces the carrier confining potential depth. For intermediate ion implantation
      doses the reduced carrier confining potential barrier combined with the non
      uniform intermixing process, that causes an increased QDas size dispersion,
      result in anomalous temperature-dependent PL properties. Indeed, the temperature
      induced PL emission energy redshift measured between 10 K and 300 K is found to
      be strongly affected by the carrier redistribution within the broadened localized
      QDas states.

PMID- 22400333
TI  - Secondary electron spectra of graphene on Ni(111) surface.
AB  - We report on kinetic energy distributions of electrons emitted during bombardment
      of graphene adsorbed on a Ni(111) surface by 0.5-0.9 keV electrons. The spectra
      reveal several peaks superimposed on the background of cascade electrons. The
      position of these peaks does not depend significantly on primary electron energy
      but show a remarkable angular dependence, indicating that they are directly
      related to the empty bands above the vacuum level of the sample.

PMID- 22400334
TI  - Ag surface diffusion and out-of-bulk segregation in CrN-Ag nano-composite
      coatings.
AB  - CrN-Ag nanocomposite coatings are deposited on Si(100) wafers and 20MnCr5 steel
      disks in a mixed Ar+N2 atmosphere by reactive magnetron sputtering. Structure,
      composition and morphology were investigated by Scanning Electron Microscopy
      (SEM), Auger Electron Spectroscopy (AES), X-ray Photoemission Spectroscopy (XPS),
      X-ray Diffraction (XRD) and Focused Ion Beam (FIB) cross sectional analysis. The
      as deposited film matrix is mainly composed by CrN phase (78%), but a relevant
      part (28%) is composed by Cr2N. Ag agglomerates in the CrN matrix forming
      elongated grains 200-400 nm wide and 50-100 nm high, which extends on the top of
      CrN columns. At the surface Ag aggregates into two different structures: large
      tetrahedral crystalline clusters, with typical dimension ranging from 200 to 500
      nm, and smaller Ag nanoparticles with diameter of 15-25 nm. The annealing in N2
      atmosphere up to 500 degrees C does not affect size and distribution of the Ag
      grains in the sub-surface region, while it induces a size increase of the bigger
      Ag clusters on the surface, mainly related to Ag surface diffusion and clusters
      coalescence. Annealing at higher temperature leads to an evident Ag out-of-bulk
      segregation, generating Ag depleted voids in the near-surface region, and further
      increasing of the Ag clusters size at the surface. Tribological tests on as
      deposited CrN-Ag film reveal a coefficient of friction against a steel ball
      reduced with respect to CrN film, probably related to the presence of Ag which
      acts as solid lubricant, but the coating is removed after a very short sliding
      distance. The poor mechanical properties of the realized Ag-based coatings are
      confirmed by lower hardness and Young modulus values with respect to pure CrN.

PMID- 22400335
TI  - Synthesis of cation-intercalated titanate nanobelts.
AB  - Monovalent, bivalent and trivalent cations of Li+, Sn2+, Al3+, Fe3+ with
      different values of electronegativity were designed as doped-ions to prepare
      cations-intercalated titanate nanobelts through ex-situ ion-exchange reaction.
      XRD results revealed that the d200 values of layered TNBs decreased as the
      following sequence: Li-intercalated TNBs > Al-intercalated TNBs > Fe-intercalated
      TNBs > Sn-intercalated TNBs. The electronegativity differences between respective
      doped-cations and oxygen can well explain the trend of the reduction of d200
      values for the synthesized layered nanobelts with different cations. The width
      change of nanobelts depending on intercalated cations showed similar tendency as
      that of d200 excluding Sn-intercalated case. That is mostly due to the
      crystallization of SnO2 nanoparticles on the nanobelts. Sn2+ is easily
      crystallized to form SnO2 nanoparticles on the surface of TNBs and being
      considered as unfavorable metal dopant for the present intercalation purpose. The
      reduction of d200 values of the doped TNBs from that of the undoped TNBs confirms
      the intercalation of the doped cations into layered structure. Such simple
      electronegativity-difference depending mechanism may be convenient for the
      designing of metal ion intercalation into octahedral TiO6 layered-oxide
      materials.

PMID- 22400336
TI  - Modeling of the laser polarization as control parameter in self-organized surface
      pattern.
AB  - To shed light on nanopattern formation upon femtosecond laser ablation, an
      adopted surface erosion model is developed, based on the description for ion beam
      sputtering. In particular, the dependence of generated patterns on the laser
      polarization is taken into account. We find that an asymmetry in deposition and
      dissipation of incident laser energy results in a respective dependence of
      coefficients in a nonlinear equation of the Kuramoto-Sivashinsky type. Surface
      morphologies obtained by this model for different polarization of the laser beam
      are presented and the time evolution of the nanopattern is discussed. A
      comparison of these numerical results with experimental data shows an excellent
      agreement. Dependence of femtosecond laser induced formation on the polarization
      of the incident beam within an adopted surface erosion model is considered. A
      continuum theory of erosion by polarized laser radiation is developed. We exploit
      the similarity to ion-beam sputtering and extend a corresponding model for laser
      ablation by including laser polarization. This yields a respective dependence of
      coefficients in a nonlinear equation of the Kuramoto-Sivashinsky type. We present
      the surface morphologies obtained by this model for different polarization of the
      laser beam and discuss a time evolution of the nanopattern. These numerical
      results are in a good agreement with numerous experimental data. We show that the
      correlation of ripples orientation with laser polarization can be described
      within a model where the polarization causes the breaking of symmetry at the
      surface. Our results support the non-linear self-organization mechanism of
      pattern formation on the surface of solids.

PMID- 22400337
TI  - Adjustable photoluminescence of peptide nanotubes coatings.
AB  - Peptide nanotubes (PNTs) have become a significant subject at the biological and
      bionanotechnology field. Here we describe the spectroscopic analysis of PNTs
      coatings, which were deposited by a physical vapor deposition technology. We show
      that we can adjust the electronic, and consequently the spectroscopic,
      photoluminescence (PL) properties of the PNT coatings, simply by changing the
      parameters of the PNT deposition. We show that by controlling the PNT deposition
      parameters we can observe different PL properties of the PNT coatings and
      significantly strengthen the PL in the visible blue region. We further explain
      that the strong blue emission is resulting from the conversion of the monomers to
      a different chemical structure. The strong blue emission, and our ability to
      adjust it, promotes the use of the PNTs as organic materials for light emitting
      devices.

PMID- 22400338
TI  - Anisotropy driven interrupted coarsening of the Asaro-Tiller-Grinfeld
      instability.
AB  - We investigate the effects of surface energy anisotropy on the coarsening
      dynamics of the Asaro-Tiller-Grinfeld instability at stake in thin semiconductor
      films. We consider a continuum model which accounts for wetting interactions
      between the film and its substrate, elasticity driven mass currents and surface
      energy anisotropy. We derive an explicit non-linear, non-local evolution equation
      for the film height that we solve numerically. Anisotropy, which dictates the
      island shapes, impacts the growth kinetics by weakening the possible elastic
      relaxation, which can lead during annealing to an interruption of Ostwald
      ripening. The resulting stationary state is characterized by square-based
      pyramids separated by a wetting layer. It is found that the instability onset is
      delayed when the film thickness decreases above the critical thickness for the
      instability to occur. We characterize the influence of the growing flux used for
      the film deposition on the stationary state reached during subsequent annealing,
      and find that the density of the resulting self-organized islands increases with
      the flux.

PMID- 22400339
TI  - Growth of germanium nanowires on silicon(111) substrates by molecular beam
      epitaxy.
AB  - Heteroepitaxial growth of Ge nanowires was carried out on Si(111) substrates by
      MBE. Au seeds were used as precursor for the VLS growth of the nanowires. Even if
      the Au droplets do not act as catalyst for the dissociation of gas, they are
      local preferential areas where the energetic barrier of Ge nucleation is lowered
      compare to the remaining non activated surface. Two sets of Au seeds were used as
      precursors for the VLS process. The first set have an average diameter of 125 nm
      and the second of 25 nm. In-situ RHEED monitoring showed a Au wetting layer
      between these seeds before the nanowires growth as well as at the end of the Ge
      nanowires growth. It means that the wetting layer acted as a surfactant from the
      Si(111) surface to the Ge grown layer between the nanowires. Analysis of SEM
      images brought the fact that the diffusion of gold from the droplets on the
      surface and the sidewalls of the nanowires via the Ostwald ripening is a key
      parameter of the growth of the nanowires.

PMID- 22400340
TI  - Local structure at Mn2+ ions in vacuum annealed small cubic ZnS nanocrystals self
      assembled into a mesoporous structure.
AB  - A mesoporous structure of self-assembled nanocrystals of cubic ZnS doped with
      Mn2+ ions with a homogeneous distribution of pores of similar size was
      synthesized at room temperature by a surfactant-assisted liquid-liquid reaction.
      The component nanocrystals exhibit a high crystallinity and a tight size
      distribution centered at 2 nm, as well as the narrowest Electron Paramagnetic
      Resonance (EPR) spectra linewidth and the best resolution reported so-far,
      effects attributed to self-assembling. The observed EPR spectra consist of lines
      from the substitutional Mn2+(I) and surface Mn2+(II) and Mn2+(III) centers. Here
      we show that, in contrast with previous reports, our EPR spectra are highly
      sensitive to structural changes during pulse annealing in vacuum up to 500
      degrees C. The changes are related to the transformation of the surface Mn2+
      centers in new Mn2+ centers, attributed to an oxidation process in which the
      thermal decomposition of the Tween 20 additive, also observed by EPR, seems to be
      involved. We have also been able to observe, for the first time by EPR
      spectroscopy, the formation of the ZnO phase and the nanocrystals size increase,
      which occur during annealing up to 500 degrees C, structural changes confirmed by
      XRD and TEM observations on the samples previously investigated by EPR.

PMID- 22400341
TI  - Preparation of core-shell ZnO-SiO2 nanowires-nanotubes for immobilization of the
      alkaline protease enzyme.
AB  - The main goal of enzyme immobilization is industrial re-use of enzymes for many
      reaction cycles. In this purpose, simplicity and improvement of the enzyme
      properties have to be strongly associated with the design of protocols of enzyme
      immobilization. In the last decade, nanosized materials have been widely used as
      a support for enzyme immobilization, for instance, silica nanotubes, phospholipid
      bilayers, self-assembled monolayers Langmuir_Blodgett films, polymer matrices,
      galleries of alpha-zirconium, phosphate, mesoporous silicates such as MCM-41,
      silica nanoparticles. In this work, we report synthesis of core shell ZnO/SiO2
      nanowires and used them as a support for immobilization of the alkaline protease.
      Characterization of this assembled systems was carried out by, Energy-dispersive
      X-ray spectroscopy (EDAX), Transmission electron microscopy (TEM) and Scanning
      electron microscopy (SEM). Biocatalytic activity of the alkaline protease in this
      bioconjugate system was examined and the results showed an increase of
      biocatalytic activity, in comparison with the free enzyme in solution.

PMID- 22400342
TI  - Functionalization of silicon dioxide surface with 3-aminopropyltrimethoxysilane
      for fullerene C60 immobilization.
AB  - Formation of self-assembled monolayers (SAM) of 3-aminopropyltrimethoxysilane
      (APTMS), chemically bonded to silicon dioxide surface, using a new solvent free
      process, has been studied by contact angle measurements, ellipsometry, ATR-FTIR
      spectroscopy and AFM imaging. The possibility of using as-obtained APTMS SAMs for
      anchoring functional molecular moieties is then studied with fullerene C60. In a
      first part we have analyzed the grafting kinetics of APTMS SAMs in order to
      control the formation of a single monolayer. Results show that about four hours
      are needed to obtain a complete APTMS single monolayer. In parallel, the ordering
      kinetics of the SAM has been monitored by ATR-FTIR spectroscopy, showing that the
      monolayer reaches its final order before grafting. We show that those APTMS SAMs
      can be used to graft C60 molecules deposited from a solution and forming about
      one monolayer anchored on amine terminal moieties. Such results could help paving
      the way to the preparation of hybrid C60-based molecular devices on silicon
      through a bottom-up approach.

PMID- 22400343
TI  - An explicit continuous analytical model for Gate All Around (GAA) MOSFETs
      including the hot-carrier degradation effects.
AB  - In this paper, an explicit and continuous analytical model including interfacial
      hot-carrier effects is developed for a deep submicron Gate All Around (GAA)
      MOSFETs. Explicit analytical expressions of the surface potential, drain current
      and transconductance are given for all operating modes. Exploiting this new
      device model, we have found that the incorporation of a high-k layer, Gate Stack
      (GS), between oxide region and gate metal leads to drain current enhancement,
      improved transconductance parameter and enhanced interfacial hot-carrier
      immunity. The developed approaches are verified and validated by the good
      agreement found with the 2D numerical simulations for wide range of device
      parameters and bias conditions. GS GAA MOSFET design can alleviate the critical
      problem and further improve the immunity of hot-carrier effects of GAA MOSFET
      based circuits in the deep submicron working domain.

PMID- 22400344
TI  - Tuning photoresponse through size control of Cu nanoparticles deposited on multi
      wall carbon nanotubes.
AB  - In this paper we illustrate a simple method for the production of multiwall
      carbon nanotubes thin films decorated with copper metal nanoparticles. The
      structural information obtained from the transmission electron microscopy study
      performed on samples differing in the quantity of deposited Copper was linked to
      the opto-electronic properties evaluated with photo-electrochemical measurements.
      The photo-response evaluated in terms of incident photon-to-charge carrier
      generation efficiency varied for different sized-Cu-multiwall carbon nanotubes
      samples across all the visible and near-ultraviolet photon energy range with
      respect to the response of bare carbon tubes. The photo-response from the sample
      covered with of 0.5 nm Cu nominal thickness, reached 10.2%, a value 2 times
      higher than that measured for bare carbon tubes of 5.9%. While this value
      decreased to 2.8% when the Cu nominal coverage thickened up to 3 nm. The increase
      in the photo-response found was interpreted as being the result of a remarkable
      charge transfer between the Cu metal nanoparticles and the carbon atoms in the
      tube due to the formation of a strong ionic bond at their interface. The results
      obtained prove that the metal nanoparticle-carbon nanotube composites have
      optical, electrical and structural properties that can be applied in a variety of
      nanoscale architectures for novel photo-electrochemical devices.

PMID- 22400345
TI  - Broadband near ultraviolet random lasing in ZnO 3-D nanowalls.
AB  - Broadband near ultraviolet (NUV) random laser was achieved by Au nanoparticle
      loaded ZnO 3-D nanowalls. Au nanoparticle was loaded on ZnO 3-D nanowalls by
      photo-chemical deposition method using ionic liquid. The optical confinement by
      the 3-D nanowalls and enhancement of incident light scattering by Au nanoparticle
      increase the number of resonant modes, and thus leading to a broadband multiple
      spectrum random lasing. The results demonstrate an important step towards to
      expand the application scope of NUV laser on medical imaging of cells, solid
      state lighting and optical sensor.

PMID- 22400346
TI  - Selective assembling of calixarenes and pseudorotaxanes on Si(100) and
      polycrystalline copper.
AB  - We report the first compared study of the anchoring mode of calix[6]arene
      derivatives and pseudorotaxanes on Si(100) and polycrystalline Cu. Calixarenes
      have been chosen for their flexibility as linkers, being, i.a., efficient
      building blocks for the constructing of molecular devices based on
      pseudorotaxanes and rotaxanes. A covalent functionalization on Si or Cu surfaces
      requires the molecules to be differently modified: thiol (-SH) or C double bond C
      terminations are respectively suitable for Cu or H-Si(100). Anchoring on Cu was
      reached by dipping a clean substrate in a calix[6]arene-SH solution, while a wet
      chemistry recipe was followed for Si(100), combined with an extra-mild
      photochemical activation via visible light. Molecular adhesion onto either
      surfaces has been demonstrated by the presence of XPS signals from specific
      elements in the molecules: calix[6]arene designed for H-Si were derivatized with
      NO2 groups on the upper rim of the calix, while the S atom was used as the
      molecular identifier on Cu. A further extension is represented by the anchoring
      reaction of rotaxanes on Si(100) and Cu surfaces. A pseudorotaxane species was
      first formed in solution by reacting a calix[6]arene "wheel," bearing three N
      phenylureido groups on the upper rim, with viologen (4,4'-bipyridinium)
      containing axle. The resulting species has then been anchored on either Cu and Si
      via its distinct termination of the axle. This two-step reaction has produced a
      threaded pseudorotaxane covalently bound to either surfaces, as shown by XPS
      results. These species are ready to respond to external stimuli. We also cross
      checked the two different anchoring groups for their reactivity on Cu and Si
      surfaces. No molecular uptake was observed when two solutions, containing
      calixarenes with the anchoring arms intended either for Si or Cu surfaces, were
      exchanged.

PMID- 22400347
TI  - [What's the physician role in Internal Medicine in hospital?].

PMID- 22400348
TI  - [Postoperative pulmonary complications: how to anticipate and prevent the risk?].
AB  - Although less studied than cardiac complications, postoperative pulmonary
      complications are frequent and serious after major surgery. A close team working
      between primary care physician, surgeon, anesthesiologist, lung and heart
      physicians is essential to prevent and reduce postoperative pulmonary
      complications. Preoperative evaluation focused on clinical data and choice of
      surgical and anaesthetic adapted techniques are the key elements for a better
      control of these risks. Postoperative lung expansion techniques can minimize rate
      and severity of respiratory complications.

PMID- 22400349
TI  - [Viral infection in acute exacerbation of COPD].
AB  - According to international recommendations, severe COPD exacerbations should be
      treated with antibiotics. However, these recommendations are based on limited
      evidence, including old studies with small group of patients. Systematic
      virological testing by RT-PCR suggests that viruses are responsible for more than
      half of these exacerbations, although the causal link is not yet clearly
      established. To date, neither clinical nor biological markers can help
      distinguish an exacerbation caused by a virus from those due to other causes.

PMID- 22400351
TI  - [COPD 2011: are there other risk factors than tobacco?].
AB  - Prevalence of COPD is under-estimated, and more so among non-smokers. Population
      studies relying on spirometry show a trend toward higher proportion of persons
      with COPD who never smoked. In Switzerland, a third of subjects with airflow
      obstruction have never smoked. Subjects with asthma, bronchial hyperreactivity
      are more at risk. Exposure to passive smoking, indoor air pollution or biological
      dusts may cause COPD. This review discusses COPD prevalence in never smokers and
      details associated risk factors.

PMID- 22400350
TI  - [Phosphate nephropathy: how to avoid it?].
AB  - Colonoscopy is a commonly used procedure for colon cancer screening. The ideal
      bowel preparation for a good visualization of the colonic mucosa would be
      effective and well tolerated. Sodium phosphate (NaP) and polyethylen glycol (PEG)
      are the two most frequently used solutions in this indication. However, although
      NaP has been described as more effective and better tolerated, it can cause
      severe acute electrolytes disturbances and, in rare cases, lead to irreversible
      renal failure, called phosphate nephropathy. NaP should therefore be prescribed
      with caution and be formally banned for patients with risk factors.

PMID- 22400352
TI  - [Intestinal microbiota, obesity and insulin resistance].
AB  - The increasing prevalence of obesity and diabetes represents one of the major
      public health problem in developed countries, leading to intensive research on
      the causes and intervention possibilities. Over the last years, intestinal flora
      became a first-line topic in this research: the development of techniques in
      molecular biology allowed a more specific approach and the elaboration of a
      genetic library of the intestinal microbiota. This article summarises acquired
      knowledge and hypothesis related to the potential role of intestinal microbiota
      in the development of obesity and insulin resistance.

PMID- 22400353
TI  - [Catheter-based treatment of drug-resistant hypertension].
AB  - The role of the sympathetic nervous system (SNS) in the control of blood pressure
      and the occurrence of hypertension has been established both in animal models and
      in clinical practice. Patients resistant to treatment are common in clinical
      practice and require a new approach to optimize blood pressure control. The
      development of a catheter-based technique to denervate the kidneys for the
      treatment of high blood pressure was introduced recently. The concept was based
      on old data of surgical renal denervation which was effective but associated with
      important morbidity. Recent data shows that catheter-based renal denervation is
      feasible and safe in humans and preliminary clinical studies are very promising.
      These data need confirmation in larger randomised controlled trials with longer
      term follow-up.

PMID- 22400354
TI  - [Trends in incidence of colorectal cancers and polyps in the Swiss canton of Vaud
      1983-2007].
AB  - Colorectal cancer is the second most frequent cancer at death and third most
      common neoplasm in Switzerland, with about 1600 deaths and 4000 new cases per
      year, respectively. This study describes the recent trends in colorectal polyps
      and cancers in the canton of Vaud where a rare population-based series on polyps
      has been available since 1983. The most salient results are the exponential
      increase in the detection rates of polyps since the late 1980s, associated with a
      doubling in the proportion of right-sided polyps, whereas colorectal cancer
      incidence remained constant over the last 25 years. The apparent paradox between
      the strong increase in detection and resection of polyps, largely due to
      screening activity, and the absence of reduction in colorectal cancer incidence
      in the Vaud population is discussed.

PMID- 22400355
TI  - [Integration of nutritional care into cancer treatment: need for improvement].
AB  - Progresses in cancer treatment transformed cancer into a chronic disease
      associated with growing nutritional problems. Poor nutritional status of cancer
      patients worsens morbidity, mortality, overall cost of care and decreases
      patients' quality of life, oncologic treatments tolerance and efficacy. These
      adverse effects lead to treatment modifications or interruptions, reducing the
      chances to control or cure cancer. Implementation of an interdisciplinary and
      longitudinal integration of nutritional care and nutritional information into
      cancer treatment (The OncoNut Program) could prevent or treat poor nutritional
      status and its adversely side effects.

PMID- 22400357
TI  - [What's your kind:" pro-innate" or "pro-acquired"?].

PMID- 22400356
TI  - [Hypochondriasis and the hypochondriacal patient].

PMID- 22400358
TI  - [Prospects for resurrection in time for Halloween].

PMID- 22400359
TI  - [Healthcare rationing? Don't even think about it].

PMID- 22400360
TI  - [Health planning recommendations in Pneumology].

PMID- 22400361
TI  - [Interstitial lung disease in rheumatoid arthritis].
AB  - Interstitial lung disease (ILD) is found in up to 30% of patients with rheumatoid
      arthritis (RA) and is clinically manifest in 5 to 10%, resulting in significant
      morbidity and mortality. The most frequent histopathological forms are usual
      interstitial pneumonia and nonspecific interstitial pneumonia. Another recently
      described presentation is combined pulmonary fibrosis and emphysema. Similarly to
      idiopathic pulmonary fibrosis, acute exacerbation of ILD may occur in RA and is
      associated with severe prognosis. Smoking is a known risk factor of RA and may
      also play a role in the pathogenesis of RA-associated ILD, in combination with
      genetic and immunologic mechanisms. Several treatments of RA may also lead to
      drug-induced ILD.

PMID- 22400362
TI  - [Late-onset asthma].
AB  - Late-onset asthma is a common disease, with characteristics that differentiate it
      from childhood asthma persisting in adults, including a heterogeneity of
      underlying mechanism, a correlation with occupational exposure and the tendency
      to chronicize. Inadequate perception of the disease importance and difficulties
      in diagnosis, due to the association to COPD, the broad differential diagnosis
      spectrum and an atypical clinical manifestation, make this disease entity
      underdiagnosed and under-treated, with consequences for morbidity and mortality.
      The treatment of adults with asthma follows the usual guidelines, but must take
      into account an occasional poor therapeutic response and the risk of side effects
      in polymorbid patients.

PMID- 22400363
TI  - [Inhaled therapies for cystic fibrosis].
AB  - Inhaled therapies play a significant role in the management of cystic fibrosis
      patients. Mucolytic and airway-rehydrating agents improve mucociliary clearance
      and respiratory functional status. Nebulized antibiotherapy achieve high local
      concentration, while reducing systemic toxicity. Tolerance to inhaled treatments
      is good excepting frequent bronchoconstriction which can usually be prevented by
      prior administration of beta2-mimetics. The majority of treatments are only
      available in liquid formulations. Thus, nebulization is the most frequently used
      inhalation mode. Vibrating-mesh nebulizers have significantly reduced inhalation
      time.

PMID- 22400364
TI  - [Latent M. tuberculosis infection, update 2011].
AB  - It is estimated that one third of the world population is latently infected by
      Mycobacterium tuberculosis and thus at risk of reactivation. Latent tuberculosis
      (TB) impact in Switzerland is often overlooked. Diagnosis and prophylaxis are
      insufficiently undertaken, especially for people at higher risk of reactivation
      due to immunosuppression. Interferon-gamma release assays replace tuberculosis
      skin tests for diagnosis of latent infection in adults. It is still recommended
      to treat prophylactically a case of latent TB infection with 9 months of
      isoniazid; however therapy with rifampicin for 4 months, currently an alternative
      option, is linked to improved adherence and favorable cost-benefit ratio.

PMID- 22400365
TI  - [Tuberculosis and HIV co-infection: a therapeutic challenge].
AB  - Tuberculosis (TB) is the most frequent opportunistic infection in patients
      infected by the Human immunodeficiency virus (HIV). The mortality related to this
      co-infection can be reduced by the early introduction of an antiretroviral
      treatment. However, when treating subjects with TB and HIV, interactions between
      antiretroviral and tuberculostatic treatments can be problematic; also, these
      patients may develop, under treatment, an immune reconstitution inflammatory
      syndrome (IRIS). This review aims to summarize the necessary therapeutic
      adjustments which should be performed when treating patients co-infected with TB
      and HIV, the most important interactions between HIV and TB treatments, and the
      medical management of the IRIS.

PMID- 22400366
TI  - [Early exercise training after exacerbation in patients with chronic respiratory
      failure].
AB  - Patients who suffered from an exacerbation of a chronic respiratory disorder are
      often very limited in terms of their exercise capacity because of severe dyspnea
      and amyotrophy of peripheral muscles. Early implementation of pulmonary
      rehabilitation may help these patients to avoid the complications of a prolonged
      bedridden period, and increase more rapidly their mobility. Early rehabilitation
      has become more frequent, but requires special skills from the care givers (chest
      therapists). Techniques which enhance muscular performance and motility of
      patients who are recovering from an exacerbation such as electromoystimulation or
      mobilisation under non-invasive ventilation, give encouraging results; their
      impact on length of hospital stay requires further studies.

PMID- 22400367
TI  - [Advance directives application in a chronic dialysis service unit:
      instructions].

PMID- 22400368
TI  - [Practical problem on ECG in elderly patient. Case #18].

PMID- 22400369
TI  - [Looks].

PMID- 22400370
TI  - [Coronary disease; French ambiguities].

PMID- 22400372
TI  - [Bioethics, miscellaneous].

PMID- 22400371
TI  - ["Nothing goes anymore" for Ginkgo biloba].

PMID- 22400373
TI  - [Government abandonment].

PMID- 22400374
TI  - [Suicidal behavior].

PMID- 22400375
TI  - [Assessment of suicidal ideation in adolescents: comparison of two instruments].
AB  - Standardized instruments are crucial for a valid assessment of suicidal behavior.
      In questionnaire assessments the wording of questions can influence the results.
      In this study we compared the congruence of the Self-Harm Behavior Questionnaire
      (SHBQ) and the Ottawa Self-Injury Inventory (OSI) as measures of prevalence of
      suicidal ideation in an adolescent sample (n = 665, mean age: 14.8, SD: 0.66). We
      found a life-time prevalence of 36.4 % in the SHBQ and a one-year-prevalence of
      27.8 % in the OSI. There was good agreement between the two instruments in terms
      of the prevalence of suicidal ideation and the association with suicide attempts.
      The observed rates are comparable with other studies in adolescents; differences
      arise with varying study designs.

PMID- 22400376
TI  - [Depression, deliberate self-harm and suicidal behaviour in adolescents engaging
      in risky and pathological internet use].
AB  - To investigate associations between risky and pathologic internet use with
      depression, deliberate self-harm and suicidal behaviour among a representative
      sample of German adolescents. A total of 1,435 students (48% boys, 52% girls)
      from the area of Heidelberg/Germany were recruited during the SEYLE study, a
      European school-based intervention study and completed an assessment of different
      questionnaires, including the Young Diagnostic Questionnaire for the assessment
      of risky and pathological internet use, the Beck Depression Inventory, the
      Deliberate Self Harm Inventory, and the Paykel Suicide Scale. 80.7% of the
      students reported regular, 14.5% risky, and 4.8% pathological internet use. The
      risky and the pathological internet users showed significant higher rates of
      depression, deliberate self-harm and suicidal behaviour compared to students with
      regular internet use. Remarkably, there were no significant differences of levels
      of depression and suicidal behaviour between risky and pathological users. These
      results suggest that not only pathologic internet use but also risky internet use
      is associated with symptoms of depression, self-harm and suicidal behaviour.
      Therefore, more attention should be paid to adolescents with risky internet use
      for the early recognition of depression, self-harm and suicidality in
      adolescence.

PMID- 22400377
TI  - [Suicidal behaviors among young adults: risk factors during development from
      early childhood to adolescence].
AB  - Suicidal behaviors are prevalent among young people. Numerous risk factors have
      been implicated in their development. In the framework of the longitudinal
      Mannheim Study of Children at Risk, 311 young adults (143 males, 168 females)
      aged 19-23 years were investigated in order 1) to determine the significance of
      different risk factors during development in predicting suicidal behaviors in
      young adulthood, 2) to identify potential risk factors discriminating between
      suicidal ideation and suicide attempts, and 3) to examine whether the effect of
      early risk factors was mediated by later occurring predictors. Young adults with
      suicidal behaviors displayed a number of abnormalities during development,
      including high load of early family adversity, suicidal ideation and psychiatric
      problems in childhood and adolescence, as well as low self esteem, poor school
      functioning, higher levels of novelty seeking, and enhanced affiliations with
      deviant peers in adolescence. Independent contributions to predicting suicidal
      behaviors in young adults were provided by early family adversity, suicidal
      ideation during childhood and adolescence, and low self esteem (with regard to
      suicidal ideation) and novelty seeking (with regard to suicide attempt),
      respectively. The impact of early adversity was mediated by child and adolescent
      externalizing disorders and low self esteem in adolescence. Possible implications
      of these findings for the prevention and treatment of suicidal behaviors are
      discussed.

PMID- 22400378
TI  - Innovation and emerging world. A journey to no-one-knows-where.

PMID- 22400379
TI  - Innovators in motion. Looking back on four years of recognizing innovative
      healthcare teams.

PMID- 22400380
TI  - Thinking big.

PMID- 22400381
TI  - Bridging the referral divide.

PMID- 22400382
TI  - Decision support.

PMID- 22400384
TI  - Innovator Awards 2012. The semi-finalist teams.

PMID- 22400383
TI  - Population health management in real time.

PMID- 22400385
TI  - The rise of the Senior nurse informaticist.
AB  - The senior clinical informatics role in patient care organizations for those with
      a nursing background--variously given the title "CNIO," "vice president of
      clinical informatics," and other labels--is increasingly becoming a nexus
      position in hospital-based organizations nationwide. Yet this position is only
      beginning to be standardized in terms of title, pay, responsibilities, and
      reporting relationships.

PMID- 22400386
TI  - Getting the message, securely.
AB  - Secure messaging is of critical interest to physicians in how they communicate
      with each other and with their patients. CIOs and other healthcare IT leaders
      speak about what they are hearing from their clinicians, and what they are doing
      to meet their requirements.

PMID- 22400387
TI  - Unsecured mobile devices: the weak link.

PMID- 22400388
TI  - Half-full or half-empty?

PMID- 22400389
TI  - [Agreements of cooperation answering a health need].

PMID- 22400390
TI  - [Implementing progressive continuing professional development].

PMID- 22400391
TI  - [Markers and references of psychological trauma].
AB  - Whether it is an isolated and violent occurrence or repetitive and invasive, the
      event at the source of a psychological trauma suddenly breaks into the
      psychological balance of a person or a group. It can take several different forms
      but always causes significant emotional shock. Untreated, it can hinder over the
      long term the development of the people concerned.

PMID- 22400392
TI  - [An emergency response to psychological suffering].
AB  - Created fifteen years ago, medical-psychological emergency units mobilise
      specialised health professionals to provide emergency care in the event of
      incidents with a significant psychological impact involving several people.
      Carried out individually or in groups, this treatment can be extended beyond the
      immediate intervention.

PMID- 22400393
TI  - [Forms of immediate medical-psychological interventions].
AB  - Immediate interventions with victims have increased over recent years. Such
      treatment requires specific clinical skills. The forms of intervention used with
      those affected (victims, witnesses, emergency response team) vary according to
      whether it involves individuals or a group of people.

PMID- 22400394
TI  - [Emergency care in transcultural situations].
AB  - In the interpersonal relationship which is present in any care relationship, the
      cultural distance between the patient and caregiver must be taken into account.
      The gestures of the patient are different, they do not really speak our language.
      This behaviour can interfere with the assessment, diagnosis or therapeutic
      alliance. Some approaches for dealing with emergency situations.

PMID- 22400395
TI  - [The specific needs of babies, children and adolescents in crises].
AB  - Medical-psychological emergency units are often called upon in situations of
      crises involving children or adolescents. Interventions are adapted to specific
      needs, taking place on a one-to-one and group basis. They are concerned with the
      child, his or her family circle and the environment in connection with the
      traumatic event.

PMID- 22400397
TI  - [Lionel Jaffres produces daily life in the theater].

PMID- 22400396
TI  - [Example of an emergency intervention].
AB  - A hospital healthcare manager, Guenaelle Jegu also works within the Val-de-Marne
      and Paris medical-psychological emergency units. Through her account, presented
      here, of the care provided to people repatriated from Haiti after the earthquake
      of January 2010, she describes the key stages of an intervention. The
      availability of caregivers and the close collaboration of the teams are necessary
      in order to provide high quality care to the victims.

PMID- 22400398
TI  - [The right to withdraw].
AB  - In the face of serious and imminent danger in a hospital, health professionals
      have the possibility of exerting their right to withdraw. The conditions for
      exercising this right are however rather restrictive and make its application
      difficult. Moreover, the withdrawal must not compromise the principle of the
      continuity of the public service. An overview of a little-known right.

PMID- 22400399
TI  - [Nurses and psychologists working in tandem in oncology].
AB  - A scheme with a nurse and psychologist working in tandem favours the development
      of interesting crossover collaboration in the care of patients suffering from
      cancer, at the end of life. The support available for patients and their family
      is thereby strengthened. By supporting each other, the caregivers are better
      equipped to deal with the emotional issues.

PMID- 22400400
TI  - [Identifying and preventing the risks of maltreatment at home].
AB  - Home nursing services have a role in supporting patients and their families or
      carers, notably with regard to the prevention of the risks of maltreatment. The
      French Red Cross in Haute-Vienne has developed, for its staff and for carers,
      theoretical and practical tools to promote proper treatment.

PMID- 22400401
TI  - [Post-emergency care in geriatrics and the promotion of short hospital stays].
AB  - With the aim of limiting hospitalisation and a possible loss of autonomy, the
      paramedical team of the post-emergency and geriatric orientation unit at Nancy
      general hospital endeavours to anticipate the life programme as soon as the
      elderly patient arrives. A daily review and close collaboration with the social
      worker are key elements in the care.

PMID- 22400402
TI  - [Supporting the patient in oncology thanks to nurse consultations].
AB  - In order to meet as best as possible the needs of patients undergoing
      chemotherapy treatment for lymphomas, a system comprising an information
      consultation and telephone follow-up was set up in the haematology department of
      Necker hospital in Paris. An original initiative involving team work which
      benefits patients and their families.

PMID- 22400403
TI  - [The role of the nurse in audiology departments].
AB  - Auditory pathologies affect the ENT sphere and require specific patient care. The
      nurse plays an essential role. At Pellegrin university hospital in Bordeaux, the
      nurses in the hearing function test centre, in addition to their nursing skills,
      have also developed expertise in audiology and are involved in training and
      research.

PMID- 22400404
TI  - First aid at a bus stop.

PMID- 22400405
TI  - [Nursing care of the patient in a toxic coma].

PMID- 22400406
TI  - [Stockholm syndrome].

PMID- 22400407
TI  - [The palliative approach].

PMID- 22400408
TI  - [Using an automated external defibrillator].

PMID- 22400409
TI  - Are pigs the right model for lipid resuscitation?

PMID- 22400410
TI  - Syringe size effect on delivered versus calculated dosages of propofol: a bench
      experiment using the Baxter InfusOR syringe pump.

PMID- 22400411
TI  - Ira P. Gunn: educator, advocate, legend.
AB  - This column examines the contributions of nurse anesthetist Ira P. Gunn, CRNA,
      MLN, FAAN (1927-2011), widely recognized as a visionary and tireless advocate for
      the profession of nurse anesthesia. Her contributions to nurse anesthesia
      practice, research, education, publication, consultation, credentialing, and
      government relations have significantly contributed to the preservation and
      advancement of nursing and nurse anesthesia.

PMID- 22400412
TI  - Management of a traumatic tracheal tear: a case report.
AB  - This case report describes a posterior tracheal tear in a healthy 8-year-old
      girl. The child sustained the injury while riding her scooter, when the
      handlebars of the scooter dislodged after running into the curb, causing the
      shaft to strike her in the manubrium of the sternum. The child presented with
      subcutaneous emphysema of the neck and the supraclavicular region bilaterally.
      Before the patient's arrival, the surgical and anesthesia team had extensive
      discussion regarding the child's perioperative management, which included the
      need to maintain spontaneous ventilation to avoid opening the tracheal tear and
      producing a further increase in the size of the pneumomediastinum. The anesthesia
      machine was prepared for a general anesthetic along with a wide array of
      appropriately sized endotracheal tubes. In addition to appropriately sized
      laryngoscope blades, a fiberoptic scope and video laryngoscope were immediately
      available. Spontaneous respirations were maintained throughout the procedure, and
      the case proceeded uneventfully. This case represents the need for proper
      preparation and communication between providers to manage all possible scenarios
      of a traumatic tracheal tear.

PMID- 22400413
TI  - Diabetic cardiac autonomic neuropathy and anesthetic management: review of the
      literature.
AB  - Cardiac autonomic neuropathy is a serious complication among diabetic patients.
      It occurs in both type 1 and type 2 diabetes, and its progression results in poor
      prognosis and increased mortality. During its course, parasympathetic and
      sympathetic nerve fibers of the cardiovascular system are damaged, resulting in
      potentially serious cardiac complications and even death. Poor glycemic control
      is believed to play a pivotal role in the pathogenesis of cardiac autonomic
      neuropathy. Its underlying etiology is not well understood; however, several
      potential pathologic mechanisms have been identified. Several clinical
      manifestations of cardiac autonomic neuropathy have been reported, including
      resting tachycardia, exercise intolerance, loss of heart rate variability,
      orthostatic hypotension, prolonged QT interval, silent ischemia, and sudden
      death. Diabetic patients exhibiting these signs and symptoms are at greater risk
      of anesthesia-related complications. A series of noninvasive autonomic tests were
      developed for the diagnosis of cardiac autonomic neuropathy, improving the
      management of diabetic patients requiring general anesthesia. These patients
      often experience cardiovascular events that may increase perioperative morbidity
      and mortality. The presence of cardiac autonomic neuropathy alters the
      hemodynamic response to induction and tracheal intubation during general
      anesthesia, resulting in intraoperative hypotension. A thorough preoperative
      assessment and vigilant monitoring perioperatively ensure successful anesthesia
      management.

PMID- 22400414
TI  - Bronchial thermoplasty: a novel treatment for severe asthma requiring monitored
      anesthesia care.
AB  - Dexmedetomidine used in monitored anesthesia care produces a safe and effective
      technique well documented in research. We report the successful use of
      dexmedetomidine for sedation during bronchial thermoplasty, a new treatment for
      patients with severe persistent asthma refractory to inhaled corticosteroids and
      long-term beta-2 agonists.

PMID- 22400415
TI  - Predictors of situation awareness in student registered nurse anesthetists.
AB  - Situation awareness (SA) is defined as one's perception of the elements of the
      environment, the comprehension of their meaning, and the projection of their
      status in the near future. The concept of SA is well known in the aviation
      industry, which is characterized by complexity and dynamism. The discipline of
      anesthesia shares these same environmental characteristics, yet the study of SA
      in this setting is in its infancy. Guided by Endsley's theory of SA, the purpose
      of this study was to provide educators with a best-evidence predictor model of SA
      in student registered nurse anesthetists (SRNAs). Seventy-one SRNAs were randomly
      selected from 3 US universities. A nonexperimental, correlational design and
      multiple regression analysis were used to measure the relationship between
      memory, cognition, and automaticity and SA. Findings from this study reveal
      cognition as the best predictor of SA in graduate SRNAs, with the addition of
      memory and automaticity contributing no additional predictive value to the model.
      The results of this study have the potential to make a positive impact on the
      admission, education, and training of SRNAs. This study contributes evidence for
      further research examining the use of high-fidelity simulation in promoting SA in
      SRNAs.

PMID- 22400416
TI  - Model for a reproducible curriculum infrastructure to provide international nurse
      anesthesia continuing education.
AB  - There are no set standards for nurse anesthesia education in developing
      countries, yet one of the keys to the standards in global professional practice
      is competency assurance for individuals. Nurse anesthetists in developing
      countries have difficulty obtaining educational materials. These difficulties
      include, but are not limited to, financial constraints, lack of anesthesia
      textbooks, and distance from educational sites. There is increasing evidence that
      the application of knowledge in developing countries is failing. One reason is
      that many anesthetists in developing countries are trained for considerably less
      than acceptable time periods and are often supervised by poorly trained
      practitioners, who then pass on less-than-desirable practice skills, thus
      exacerbating difficulties. Sustainability of development can come only through
      anesthetists who are both well trained and able to pass on their training to
      others. The international nurse anesthesia continuing education project was
      developed in response to the difficulty that nurse anesthetists in developing
      countries face in accessing continuing education. The purpose of this project was
      to develop a nonprofit, volunteer-based model for providing nurse anesthesia
      continuing education that can be reproduced and used in any developing country.

PMID- 22400417
TI  - Anesthetic management of a patient undergoing an ex utero intrapartum treatment
      (EXIT) procedure: a case report.
AB  - The ex utero intrapartum treatment (EXIT) procedure involves partial delivery of
      the fetus with the fetal-placental circulation maintained. This allows for
      management of the obstructed fetal airway via direct laryngoscopy, bronchoscopy,
      tracheostomy, or surgical intervention. These complex and often challenging
      procedures have been performed about 100 times in the United States to date.
      Recent advances in prenatal diagnosis of fetal congenital malformations, in
      particular, abnormalities involving the fetal airway, have allowed for the
      development of the EXIT strategy to convert potentially catastrophic situations
      during fetal delivery to a controlled environment. Indications for the EXIT
      procedure have expanded to a variety of congenital abnormalities, including fetal
      neck masses, lung or mediastinal tumors, congenital high airway obstruction
      syndrome, conjoined twin separation, and acute respiratory distress syndrome
      requiring transitioning from EXIT to extracorporeal membrane oxygen
      transitioning. Various considerations must be managed by the anesthesia provider
      during the EXIT procedure to ensure positive maternal and fetal outcomes. Careful
      attention to achieving adequate uterine relaxation, maintaining maternal blood
      pressure, avoiding placental abruption, prioritizing fetal airway establishment,
      and providing return of uterine tone when indicated are examples of these
      considerations. In this case report, a parturient presented for an EXIT procedure
      secondary to fetal cystic hygroma.

PMID- 22400418
TI  - Complex regional pain syndrome: a review of diagnostics, pathophysiologic
      mechanisms, and treatment implications for certified registered nurse
      anesthetists.
AB  - The pathophysiologic mechanisms for complex regional pain syndrome (CRPS) are
      complex and elusive. The proposed etiologic mechanisms for CRPS include
      inflammatory responses, peripheral or central sensitization, and sympathetic
      dysfunction. Anesthesia care of patients with CRPS is challenging. Treatments
      including physiotherapy, peripheral vasodilators, sympathetic blockade,
      analgesics, and other systemic medications can help optimize mobility, perfusion,
      and pain relief for affected patients.

PMID- 22400419
TI  - Jizz and the joy of pattern recognition: virtuosity discipline and the agency of
      insight in UK naturalists' arts of seeing.
AB  - Approaches to visual skilling from anthropology and STS have tended to highlight
      the forces of discipline and control in understanding how shared visual accounts
      of the world are created in the face of potential differences brought about by
      multi-sensorial perception. Drawing upon a range of observational and interview
      material from an immersion in naturalist training and biological recording
      activities between 2003 and 2009, I focus upon jizz, a distinct form of gestalt
      perception much coveted by naturalist communities in the UK. Jizz is described as
      a tacit and embodied way of seeing that instantaneously reveals the identity of a
      species, relying upon but simultaneously suspending the arduous and meticulous
      study of an organism's diagnostic characteristics. I explore the potential and
      limitations of jizz to allow for both visual precision and an enchanted and
      varied form of encounter with nature. In so doing, I explore how the specific
      characteristics of wild, intangible and irreverent virtuoso performance work
      closely together with disciplining taxonomic standards. As such, discipline and
      irreverence work together, are mutually enabling, and allow for an accommodation
      rather than a segregation of potential difference brought about by perceptual
      variety.

PMID- 22400420
TI  - Documenting the doable and doing the documented: bridging strategies at the UK
      Stem Cell Bank.
AB  - We explore the local negotiation of regulatory practice at the UK Stem Cell Bank,
      the first Bank of its type in the world. Basing our empirical work on a detailed
      analysis of one aspect of the Bank's regulatory commitment--the completion of the
      Cell Line Information form--we make visible the necessary judgements and labour
      involved in interpreting and operationalizing externally imposed regulation. The
      discussion opens by detailing the problems encountered when the Bank completes
      the form: reconciling a bureaucratic system of accountability with craft-like
      laboratory skills involving multiple kinds of tacit knowledge. We follow this by
      explicating the emergent 'bridging strategies' pursued by the Bank to address
      these issues, highlighting their reliance upon the formation of trust and social
      networks. The closing discussion emphasizes the contingent assembly of regulatory
      practices that emerge in the local setting.

PMID- 22400421
TI  - Artefacts of not-knowing: the medical record, the diagnosis and the production of
      uncertainty in Papua New Guinean biomedicine.
AB  - Anthropological and STS scholars of biomedical work have traditionally explored
      contexts where inconsistencies and lacunas in diagnostic knowledge-production are
      problematic for medical practitioners, and such scholars have consequently
      focused on the social and political processes by which such epistemic
      uncertainties are resolved. This article draws on ethnographic material from a
      Papua New Guinean hospital where diagnostic uncertainty is not rendered
      problematic and where the open-endedness of the diagnostic process gives rise to
      new forms of medical expertise and practice. The paper focuses on the medical
      record as an artefact of not-knowing that both documents and performs uncertainty
      as a valuable resource. It shows that medical records can operate as either
      technologies of 'opening' that multiply opportunities for pragmatic action within
      a hospital space or as technologies of 'closure' that move people and documents
      between spaces. Practices of not-knowing and knowing are therefore shown to be
      interdependent and interchangeable 'moments' of bureaucratic-biomedical work.

PMID- 22400422
TI  - Rediscovering radiology: new technologies and remedial action at the worksite.
AB  - This study contributes to social studies of imaging and visualization practices
      within scientific and medical settings. The focus is on practices in radiology,
      which are bound up with visual records known as radiographs. The study addresses
      work following the introduction of a new imaging technology, tomosynthesis. Since
      it was a novel technology, there was limited knowledge of how to correctly
      analyse tomosynthesis images. To address this problem, a collective review
      session was arranged. The purpose of the present study was to uncover the
      practical work that took place during that session and to show how, and on what
      basis, new methods, interpretations and understandings were being generated. The
      analysis displays how the diagnostic work on patients' bodies was grounded in two
      sets of technologically produced renderings. This shows how expertise is not
      simply a matter of providing correct explanations, but also involves discovery
      work in which visual renderings are made transparent. Furthermore, the results
      point to how the disciplinary knowledge is intertwined with timely actions, which
      in turn, partly rely on established practices of manipulating and comparing
      images. The embodied and situated reasoning that enabled radiologists to discern
      objects in the images thus display expertise as inherently practical and domain
      specific.

PMID- 22400423
TI  - When a robot is social: spatial arrangements and multimodal semiotic engagement
      in the practice of social robotics.
AB  - Social roboticists design their robots to function as social agents in
      interaction with humans and other robots. Although we do not deny that the
      robot's design features are crucial for attaining this aim, we point to the
      relevance of spatial organization and coordination between the robot and the
      humans who interact with it. We recover these interactions through an
      observational study of a social robotics laboratory and examine them by applying
      a multimodal interactional analysis to two moments of robotics practice. We
      describe the vital role of roboticists and of the group of preverbal infants, who
      are involved in a robot's design activity, and we argue that the robot's social
      character is intrinsically related to the subtleties of human interactional moves
      in laboratories of social robotics. This human involvement in the robot's social
      agency is not simply controlled by individual will. Instead, the human-machine
      couplings are demanded by the situational dynamics in which the robot is lodged.

PMID- 22400424
TI  - Greek alchemists at work: 'alchemical laboratory' in the Greco-Roman Egypt.
AB  - The paper focuses on the alchemical laboratory of ancient Greco-Egyptian
      alchemists, by taking into account especially the earliest alchemical texts (both
      in the Greek and in the Syriac tradition), ascribed to Pseudo-Democritus, Maria
      the Jewish and Zosimus. The first part analyzes the possible relationships
      between the workshops of Egyptian craftsmen (first of all, dyers, metals workers
      and glass workers) and the activity of the alchemists. The second part gives a
      general overview on the alchemical instruments described in the Corpus
      alchemicum.

PMID- 22400425
TI  - Multa curiosa: Vallisneri's early studies on earth sciences.
AB  - In 1687, after he graduated in Medicine, young Antonio Vallisneri (1661-1730)
      returned in the Duchy of Modena and Reggio. In those years he mainly served as
      general practitioner; nevertheless, he also devoted many studies to various
      aspects of the natural sciences. He performed many observations, accurately
      reporting them in seven Quaderni, which were compiled between 1694 and 1701.
      Though the Earth sciences occupy only a small part of these diaries, the accuracy
      of the notes makes them a precious token of the scientific praxis adopted by the
      author in this field of study. This paper deals with the analysis of these early
      geological reports, pointing out the main criteria of Vallisneri's experimental
      method and paying attention to the great significance which these documents had
      in the elaboration of some of his published works.

PMID- 22400426
TI  - Beyond the ration: sharing and scrounging on the western front.
AB  - The assumption to date has been that military provisioning was an unmitigated
      success for the British Army of the First World War; a judgement not reflected in
      the accounts of many of the rank and file soldiers on the Western Front. The men
      were often disappointed not merely by shortfalls, but also by rations that,
      though high in calories, failed to tempt the palate or reflect the civilian meals
      that had shaped their eating preferences. Whether driven by hunger or boredom,
      supplementing the official diet was a regular occupation for the men, through
      parcels from home, visits to the canteens or less legitimate means. Scrounging
      opportunities ranged from apples scrumped in a French orchard and an
      opportunistic raid on a chicken coop, to the pilfering of army stores. This
      article demonstrates the extent of the role played by this extra food in the
      men's diet and explores the significance of the way in which it was obtained and
      consumed. Whatever the source of the food, its even-handed division was a subject
      repeatedly referenced in the soldiers' diaries, letters, and memoirs. The sharing
      of food between pals in a just and proper fashion re-created, to some small
      degree, a microcosm of an ordered, civilized world in the ranks.

PMID- 22400427
TI  - The Buchanan Report, environment and the problem of traffic in 1960s Britain.
AB  - Traffic congestion in Britain's towns and cities grew with the exponential rise
      of car ownership in the 1950s and 1960s. The Buchanan Report, Traffic in Towns
      (1963), was a pioneering response to this problem, advancing a series of radical
      solutions for how cities could be adapted to mass car ownership. This article
      examines the contemporary debate about traffic among planners and politicians in
      the 1960s and considers both short-term responses to the Buchanan Report and its
      longer term effects in cities such as Leeds and Leicester. The legacy of Buchanan
      was ambivalent: while many of its prescriptions favoured a new, environmentally
      sensitive approach to the historic fabric and urban living, the report's
      arguments for radical reconstruction pointed to the building of urban motorways.
      Paradoxically, the growth of environmental awareness in 1960s Britain was linked
      to the endeavour to modernize the nation's towns and cities and to create the
      conditions for a car-owning society.

PMID- 22400428
TI  - [Cancer according to plan].

PMID- 22400429
TI  - [Treatment of endometriosis].
AB  - Endometriosis is one of the frequent gynecological diseases in premenopausal
      women. The clinical diagnostics is difficult because symptoms of endometriosis
      are variable. The surgical removal of endometriosis is the primary therapeutic
      aim. Medical treatment plays a very important role in the therapy of this chronic
      disease. A symptomatic therapy by analgetics should be combined with a hormonal
      treatment. The use of oral contraceptives in extended cycle or long-term use is
      effective against endometriosis associated pain. Progestogens, especially
      dienogest, which is licensed for endometriosis treatment and good investigated,
      are very effective and also available for long-term use. GnRH-analogues are
      effective for a short-term treatment (duration of 3 months). The long-term
      treatment with GnRH-analogues should only be used in selected cases and in
      combination with an add back therapy. Treatment of endometriosis should be
      planned individually for each patient, dependent on stage, localization and
      activity of endometriosis and further family planning. By the combination of
      hormonal and operative treatment possibilities a maximum period free of pain or
      recurrence of endometriosis can be reached.

PMID- 22400430
TI  - [Antiviral treatment of chronic hepatitis C].
AB  - The therapy of the chronically hepatitis C virus infection is still a major
      challenge for the attending physician. Standard therapy regimen implements the
      combination of pegylated interferon alpha and ribavirin. Duration of therapy is
      individualized according to the infecting HCV genotype and on the viral response.
      However, only in 50-80% (dependent on the HCV genotype) treatment will be
      successful. The development of so called "direct-acting antivirals"(DAA) will
      provide new options and this was achieved by the approval of two inhibitors of
      the HCV protease. Boceprevir and telaprevir give hope especially for patients
      infected with the worse to treat HCV genotype 1. In order to reduce the risk of
      antiviral resistance these drugs are given in combination with pegylated
      interferon and ribavirin only.

PMID- 22400431
TI  - [New guideline for the treatment of diabetes mellitus type 1].

PMID- 22400432
TI  - A tribute to Mike Vance the dean of human development.

PMID- 22400433
TI  - Getting the right people on the bus.

PMID- 22400434
TI  - Home care: changes and concerns.

PMID- 22400435
TI  - Employee engagement: the linchpin to a successful, high reliability home health
      agency.

PMID- 22400436
TI  - Survival of the fittest: proven strategies to recruit, train, and retain the best
      sales professionals.

PMID- 22400437
TI  - Respect and recognition: the keys to keeping boomers on the job.

PMID- 22400438
TI  - Social media in the workplace: no employer is immune.
AB  - The "traditional" notion of social media in the workplace as employees logging on
      to Facebook for personal use from their desks is long gone. Social media, in some
      form or another, is now present in virtually every workplace, regardless of where
      employees perform their work.

PMID- 22400439
TI  - Care coordination: Key to providing timely treatment, rehabilitation for elderly,
      at-risk patients.

PMID- 22400440
TI  - New year's resolutions: planning and reassessing services for the year ahead.

PMID- 22400442
TI  - What your staff needs to know about hospice discharges.

PMID- 22400443
TI  - Wandering: a common challenging behavior.

PMID- 22400444
TI  - Die with dignity.

PMID- 22400445
TI  - Caring: the key to employee retention.

PMID- 22400446
TI  - Mammalian CNS barosensitivity: studied by brain-stem auditory-evoked potential in
      mice.
AB  - High pressure nervous syndrome (HPNS) is an instinctive response of mammalian
      high-class nervous functions to increased hydrostatic pressure.
      Electrophysiological activity of mammalian central nervous system (CNS),
      including brainstem auditory-evoked potential (BAEP), has characteristic changes
      under pressure. Here we recorded BAEP of 63 mice exposed to 0-4.0 MPa. The
      results showed that interpeak latencies between wave I and wave IV (IPL1-4) and
      their changes under pressures (deltaIPL1-4) responded to increasing pressure in a
      biphase pattern, shortened under pressure from 0 to 0.7MPa, then prolonged later.
      There were significantly negative correlations between base IPL1-4s and deltaIPL1
      4s (p < 0.01). Individual IPL1-4s were supposed to respond to increasing pressure
      in a relative steady pattern in accordance with its base IPL1-4s. Those with
      shorter-base IPL1-4 presented direct increases in IPL1-4. However, those with
      longer-base IPL1-4 had a decreased IPL1-4 under small to moderate pressure then
      rebounded later. Our results suggested that mammalian CNS functions were
      susceptible to small to moderate pressure, as well as a higher pressure than
      1.0MPa. Mice, as a statistical mass, had an "optimum" pressure about 0.7MPa,
      rather than atmospheric pressure, referred as shortest IPL1-4s. An individual's
      response to high pressure might be relied on his base biological condition. Our
      results highlighted a new approach to investigate a practical strategy to medical
      selecting barotolerant candidates for deep divers. Diversity of individual
      susceptibility to hydrostatic pressure was under discussed. Underlying mechanisms
      of the "optimum" pressure for CNS function and its significance to
      neurophysiology remain open to further exploration.

PMID- 22400447
TI  - Does inert gas narcosis have an influence on perception of pain?
AB  - The effect of an increased nitrogen partial pressure under hyperbaric conditions
      is known as nitrogen narcosis (NN). At an ambient pressure of about 4 bar,
      reduced cognitive performance as well as euphoric effects are reported. We
      examined the effect of NN on pain perception. 22 subjects completed an
      experimental (50 meters = 6 bar) and a simulated control dive (0 m = 1 bar) in a
      hyperbaric chamber. Before and during each dive a standardized cold pressure test
      was performed. The intensity of pain perceived was assessed with the help of a
      visual analogue scale; additionally, subjects assessed the subjective effect of
      NN. The study showed that the perceived pain intensity is significantly reduced
      under nitrogen narcosis conditions (F1.21 = 5.167, p < 0.034) when compared to
      the perceived pain intensity under the control dive conditions (F1.21 = 0.836, p
      = 0.371). A connection between perceived pain intensity and subjects experience
      of the NN was not found under the experimental dive condition (r = 0.287, p =
      0.195). We could show that even relatively moderate hyperbaric conditions may
      have an influence on the perception of pain. The results are highly relevant
      since nitrogen narcosis occurs in divers as well as in medical personnel or
      construction workers, working under hyperbaric conditions.

PMID- 22400448
TI  - Venous gas embolism after an open-water air dive and identical repetitive dive.
AB  - Decompression tables indicate that a repetitive dive to the same depth as a first
      dive should be shortened to obtain the same probability of occurrence of
      decompression sickness (pDCS). Repetition protocols are based on small numbers, a
      reason for re-examination. Since venous gas embolism (VGE) and pDCS are related,
      one would expect a higher bubble grade (BG) of VGE after the repetitive dive
      without reducing bottom time. BGs were determined in 28 divers after a first and
      an identical repetitive air dive of 40 minutes to 20 meters of sea water. Doppler
      BG scores were transformed to log number of bubbles/cm2 (logB) to allow numerical
      analysis. With a previously published model (Model2), pDCS was calculated for the
      first dive and for both dives together. From pDCS, theoretical logBs were
      estimated with a pDCS-to-logB model constructed from literature data. However,
      pDCS the second dive was provided using conditional probability. This was
      achieved in Model2 and indirectly via tissue saturations. The combination of both
      models shows a significant increase of logB after the second dive, whereas the
      measurements showed an unexpected lower logB. These differences between
      measurements and model expectations are significant (p-values < 0.01). A reason
      for this discrepancy is uncertain. The most likely speculation would be that the
      divers, who were relatively old, did not perform physical activity for some days
      before the first dive. Our data suggest that, wisely, the first dive after a
      period of no exercise should be performed conservatively, particularly for older
      divers.

PMID- 22400449
TI  - Inner ear decompression sickness in compressed-air diving.
AB  - INTRODUCTION: Inner ear decompression sickness (IEDCS) has become more frequently
      reported in recreational diving. METHODS: We examined 34 divers after IEDCS and
      analyzed their dive profiles, pattern of symptoms, time of symptom onset and the
      association with a right-to left shunt (r/l shunt). RESULTS: Four divers used
      mixed gas and were excluded from the analysis. Of the remaining 30 divers, 25
      presented with isolated IEDCS alone, while five divers had additional skin and
      neurological symptoms. All divers presented with vertigo (100%), and 12 divers
      reported additional hearing loss (40%). All symptoms occurred within 120 minutes
      (median 30 minutes) of ascent. Twenty-two of 30 divers (73.3%) showed a r/l
      shunt. CONCLUSION: A possible explanation for the frequent association of a r/l
      shunt and the dominance of vestibular rather than cochlear symptoms could be
      attributed to the different blood supply of the inner ear structures and the
      different size of the labyrinthine compartments. The cochlea has a blood supply
      up to four times higher than the vestibular part of the inner ear, whereas the
      vestibular fluid space is 30% larger. The higher prevalence of symptoms
      referrable to the less well-perfused vestibular organ provides further evidence
      that persistent local inert gas supersaturation may cause growth of incoming
      arterial bubbles and may therefore be an important pathophysiological factor in
      IEDCS.

PMID- 22400450
TI  - Is the rate of whole-body nitrogen elimination influenced by exercise?
AB  - BACKGROUND: Because it has earlier been shown that exercise 24 or two hours pre
      dive may suppress the appearance of venous gas bubbles (VGB) in connection with
      the dive, we studied whether exercise before or during N2 elimination would
      influence the rate of the latter. Nitrogen elimination was recorded in eight
      volunteers breathing a normoxic O2+argon mixture for two hours. The N2 washout
      was preceded two (Condition A) or 24 hours (Condition B) earlier, by one hour of
      exercise at 85% VO2max (two hours of exercise interspersed with two hours of
      rest). In separate experiments, exercise at -40% of VO2max was performed
      throughout the two-hour washout (Condition C), and control experiments (Condition
      D) with denitrogenation without exercise were also performed. RESULTS: There were
      no significant differences among conditions for the total N2 eliminated (904 +/-
      196 mL). The half-times of N2 washout for A (35.2 +/- 10.8 minutes) and B (31.9
      +/- 8.6 minutes) did not differ from control washouts. The rate of washout in C
      increased 14% compared to D (half-time: 30.4 +/- 7.6 vs. 34.5 +/- 7.8 minutes, p
      = 0.002), and correlated with cardiac output. CONCLUSION: Exercise 24 or two
      hours pre-N2 washout did not affect it, suggesting that the decreased VGB scores
      noted by others in dives preceded by conditions similar to A and B are not due to
      changes in nitrogen exchange but rather to factors related to bubble formation
      and/or appearance. That N2 elimination is enhanced by concomitant exercise makes
      physiological sense but does not necessarily explain the observation by others of
      a reduced risk of decompression sickness with exercise before diving.

PMID- 22400451
TI  - Nitrox permits direct exit for attendants during extended hyperbaric oxygen
      treatment.
AB  - BACKGROUND: Intermittent breathing of oxygen-enriched air, nitrox (1:1
      air:oxygen, 60.5% O2), for attendants in multiplace hyperbaric chambers should
      enable treatment protocols (HOPAN - hyperbaric oxygen protocol attendants'
      nitrox) of up to 200 minutes at 2.8 atmospheres absolute (ATA), while retaining
      the option of a direct decompression and exit. METHODS: HOPAN with cycles of 15
      minutes of nitrox breathing followed by 10 minutes of chamber air for attendants
      were occasionally used from 2007-2009. HOPAN vs. LTP (local treatment protocols)
      were evaluated via an anonymous enquiry among attendants; patients' medical
      records were followed six months post-HBO2 treatment (HBO2T). RESULTS: 88 HOPANs,
      with 59 chamber attendants assisting 30 patients, were documented. HOPAN duration
      ranged from 55-167 minutes (median 140 minutes). 31/59 attendants answered the
      enquiry. Perceived comfort of each protocol (HOPAN vs. LTP) by attendants was
      reported as equal. Symptoms, both minor (parestesias) and severe (joint pain),
      were reported in connection with LTP, while only one occurrence (mild joint pain)
      was reported in connection with HOPAN. No complications were documented among the
      attendants or the patients. It is suggested that nitrox breathing for chamber
      attendants provide flexible HBO2T for patients at 2.8 ATA for up to 200 minutes
      within no-decompression limits, facilitating future studies of HBO2T dosage.

PMID- 22400452
TI  - Anaphylactic shock during hyperbaric oxygen therapy.
AB  - A case of a 38-year-old woman is reported who was treated with hyperbaric oxygen
      therapy to cure a dehiscent wound. She suffered from "oral-allergy syndrome"
      (OAS) while eating certain fruits, and from itching when wearing latex gloves to
      handle hair dyes. Fifteen minutes after the start of compression, malaise,
      anxiety, dyspnoea, tachycardia, cold sweating and laryngeal stridor occurred.
      Despite intensive care treatment, face angioedema persisted for several days. On
      the basis of history, radioallergosorbent test (RAST) and prick tests, latex was
      assumed to be responsible for the anaphylactic reaction. To our knowledge, this
      is the first extensive report of an anaphylactic reaction to latex in a
      hyperbaric chamber. The lesson drawn from this case record can be summarized as
      follows: 1) never fail to collect a thorough history; 2) set up a latex-safe
      hyperbaric chamber when needed; 3) have an emergency kit always near at hand.

PMID- 22400453
TI  - Claustrophobia during routine hyperbaric oxygen treatment.

PMID- 22400454
TI  - The action of nitrogen on glutamate concentration: adding to the discussion.

PMID- 22400455
TI  - Growing roots: Native American evidence-based practices. Introduction.

PMID- 22400456
TI  - Indigenous communities and evidence building.
AB  - Indigenous populations in the U.S. and Pacific Islands are underrepresented in
      mental health and substance abuse research, are underserved, and have limited
      access to mainstream providers. Often, they receive care that is low quality and
      culturally inappropriate, resulting in compromised service outcomes. The First
      Nations Behavioral Health Association (U.S.) and the Pacific Substance Abuse and
      Mental Health Collaborating Council (Pacific Jurisdictions), have developed a
      Compendium of Best Practices for American Indian/Alaska Native and Pacific Island
      Populations. The private and public sector's increasing reliance on evidence
      based practices (EBP) leaves many Indigenous communities at a disadvantage. For
      example, funding sources may require the use of EBP without awareness of its
      cultural usefulness to the local Indigenous population. Indigenous communities
      are then faced with having to select an EBP that is rooted in non-native social
      and cultural contexts with no known effectiveness in an Indigenous community. The
      field of cultural competence has tried to influence mainstream research, and the
      escalating requirement of EBP use. These efforts have given rise to the practice
      based evidence (PBE) and the community-defined evidence (CDE) fields. All of
      these efforts, ranging from evidence-based practice to community-defined
      evidence, have a shared goal: practice improvement.

PMID- 22400457
TI  - A constructive Indian country response to the evidence-based program mandate.
AB  - Over the last 20 years governmental mandates for preferentially funding evidence
      based "model" practices and programs has become doctrine in some legislative
      bodies, federal agencies, and state agencies. It was assumed that what works in
      small sample, controlled settings would work in all community settings,
      substantially improving safety, effectiveness, and value-for-money. The evidence
      based "model" programs mandate has imposed immutable "core components," fidelity
      testing, alien programming and program developers, loss of familiar programs, and
      resource capacity requirements upon tribes, while infringing upon their tribal
      sovereignty and consultation rights. Tribal response in one state (Oregon) went
      through three phases: shock and rejection; proposing an alternative approach
      using criteria of cultural appropriateness, aspiring to evaluability; and
      adopting logic modeling. The state heard and accepted the argument that the
      tribal way of knowing is different and valid. Currently, a state-authorized
      tribal logic model and a review panel process are used to approve tribal best
      practices for state funding. This constructive response to the evidence-based
      program mandate elevates tribal practices in the funding and regulatory world,
      facilitates continuing quality improvement and evaluation, while ensuring that
      practices and programs remain based on local community context and culture. This
      article provides details of a model that could well serve tribes facing evidence
      based model program mandates throughout the country.

PMID- 22400458
TI  - Historical trauma among Indigenous Peoples of the Americas: concepts, research,
      and clinical considerations.
AB  - Indigenous Peoples of the Americas have experienced devastating collective,
      intergenerational massive group trauma and compounding discrimination, racism,
      and oppression. There is increasing evidence of emotional responses to collective
      trauma and losses among Indigenous Peoples, which may help to inform ways of
      alleviating psychological suffering and unresolved grief. Tribal cultural and
      regional differences exist which may impact how the wounding across generations
      and within an individual's lifespan are experienced and addressed. This article
      will review the conceptual framework of historical trauma, current efforts to
      measure the impact of historical trauma upon emotional distress, and research as
      well as clinical innovations aimed at addressing historical trauma among American
      Indians/Alaska Natives and other Indigenous Peoples of the Americas. We will
      discuss assessment of historical trauma and implications for research and
      clinical as well as community interventions, and conclude with recommendations.

PMID- 22400459
TI  - American Indian culture as substance abuse treatment: pursuing evidence for a
      local intervention.
AB  - Contemporary tribal commitments to traditional cultural reclamation and
      revitalization find continued expression by recent generational cohorts of
      American Indians who, when it comes to matters of recovery, healing, and wellness
      in the context of substance abuse, routinely assert that "our culture is our
      treatment." And yet, empirical investigations of this culture-as-treatment
      hypothesis--namely, that a (post)colonial return to indigenous cultural
      orientations and practices is sufficient for effecting abstinence and recovery
      from substance use disorders for many American Indians--have yet to appear in the
      scientific literature. Preliminary activities of a research partnership dedicated
      to the empirical exploration of this hypothesis for reducing Native American
      substance use disorders are summarized. Specifically, collaboration between a
      university-based research psychologist and a reservation-based substance abuse
      treatment program staff has thus far resulted in a detailed blueprint for a
      radically alternative, culturally-grounded intervention developed for reservation
      residents. This proposed alternative intervention--a seasonal cultural immersion
      camp designed to approximate the day-to-day experiences of prereservation
      ancestors--was designed for eventual implementation and evaluation with adult
      clients referred for residential treatment on the Blackfeet Indian reservation.
      It is anticipated that the proposed intervention will eventually afford empirical
      evaluation of the culture-as-treatment hypothesis.

PMID- 22400460
TI  - Reclaiming our roots: accomplishments and challenges.
AB  - Best practices for Native Americans are rooted in culture. However, reclaiming
      best practices is a challenge given the genocidal policies that outlawed Native
      culture. Despite this challenge Native people have proven resilient in restoring
      culture. The Native American Health Center in Oakland, California, has made
      cultural interventions an option for an urban, intertribal and sometimes
      multiracial Native American population to create and maintain their health on a
      spiritual, emotional, mental and physical level. Nevertheless, sustaining these
      cultural options to maintain health continues to be a challenge. While the
      passage of the Mental Health Services Act (MHSA) in 2004 in California to
      transform treatment of mental and behavioral health "as we know it" would seem to
      create a gateway for cultural options, mainstream mental health has a hard time
      perceiving cultural interventions as a viable means to treat mental illness and
      maintain wellness. Frequently, the author has attended meetings of decisionmaking
      bodies that oversee how MHSA money is spent and someone will blurt out after
      someone has described an innovative cultural intervention "What does that have to
      do with mental illness?" The following article discusses how the clash of the two
      cultures, Native and mainstream, continues to be a challenge for sustained
      funding to implement culturally competent programs.

PMID- 22400461
TI  - Holistic System of Care: a ten-year perspective.
AB  - The Holistic System of Care for Native Americans in an Urban Environment is a
      community-focused intervention that provides behavioral health care, promotes
      health, and prevents disease. This approach is based on a community strategic
      planning process that honored Native American culture and relationships.
      Substance abuse, mental illness, homelessness, poverty, crime, physical illness,
      and violence are symptoms of historical trauma, family dysfunction, and spiritual
      imbalance. The holistic model links treatment, prevention, and recovery. The link
      between prevention and treatment is early intervention. Peer support is the link
      between treatment and recovery. Recovering individuals serve as role models
      linking recovery to prevention. Culture and spirituality build a strong and
      resilient foundation for recovery. This article documents the effectiveness of
      the holistic model over a ten-year period that it has been implemented at the
      Family & Child Guidance Clinic of the Native American Health Center in the San
      Francisco Bay Area. The holistic model has produced statistically significant
      reductions in substance abuse among adult Native American women, men, reentry,
      and homeless populations; reductions in substance abuse among Native American
      adolescents; reductions in HIV/AIDS high-risk behavior among Native American men,
      women, and adolescents; and decreases in acting out behavior among Native
      American severely emotionally disturbed children.

PMID- 22400462
TI  - Honoring children, making relatives: the cultural translation of parent-child
      interaction therapy for American Indian and Alaska Native families.
AB  - The Indian Country Child Trauma Center, as part of the National Child Traumatic
      Stress Network, designed a series of American Indian and Alaska Native
      transformations of evidence-based treatment models. Parent-Child Interaction
      Therapy (PCIT) was culturally adapted/translated to provide an effective
      treatment model for parents who have difficulty with appropriate parenting skills
      or for their children who have problematic behavior. The model, Honoring Children
      Making Relatives, embeds the basic tenets and procedures of PCIT in a framework
      that supports American Indian and Alaska Native traditional beliefs and parenting
      practices that regard children as being the center of the Circle. This article
      provides an overview of the Honoring Children-Making Relatives model, reviews
      cultural considerations incorporated into ICCTC's model transformation process,
      and discusses specific applications for Parent-Child Interaction Therapy within
      the model.

PMID- 22400463
TI  - From tradition to evidence: decolonization of the evidence-based practice system.
AB  - Culture counts in the prevention and treatment of behavioral ailments. The Native
      American Health Center (NAHC) has successfully developed a model that
      incorporates cultural adaptations into EBPs, yet also believes community-defined
      and practice-based evidence are relevant in the validation of traditional
      practices. American Indian/Alaska Native (AI/AN) traditional practices are more
      than complementary forms of healing. They are stand-alone methods, developed and
      used by tribal people long before the concept of EBPs existed. There is a need
      for funders to respect these practices as autonomous mental health strategies.
      The reasons for promoting change are explained through an understanding of key
      dimensions of AI/AN behavioral health issues. These key dimensions were
      identified in the 2001 Surgeon General's Report and an extensive literature
      review of Indigenous research methodologies. Recommendations are made based upon
      their ability to promote AI/AN empowerment, to support movement toward self
      determination using the Indigenous Research Agenda model. This model honors fluid
      movement of Indigenous people through states of survival, recovery, development
      and self-determination through four categories for action: decolonization,
      mobilization, transformation, and healing. The end results are options for
      holistic approaches to influence policy changes in the EBP system.

PMID- 22400464
TI  - Demonstrating the process of community innovation: the Indian Country
      Methamphetamine Initiative.
AB  - In 2007 the federal Department of Health and Human Services, Office for Minority
      Health, collaborating with other federal agencies, sponsored the Indian Country
      Methamphetamine Initiative (ICMI). ICMI was undertaken to create community
      driven, culture-based best practices in methamphetamine prevention and treatment
      which could then be disseminated throughout Indian Country. The ICMI ultimately
      involved ten tribes and five national organizations. Each tribe established a
      coalition of community government, nongovernment agencies, and elements of civic
      society to develop a comprehensive assessment, plan, and then to implement the
      plan. Each tribal coalition planned a complex array of activities including
      treatment programs, public education and mobilization, law enforcement
      strategies, and other intervention strategies, each intervention described within
      a logic model. These interventions focused on logic modeling; coalitions;
      capacity development and service system optimization; law enforcement and
      justice; individual and family treatment; public information, awareness, and
      education; community mobilization; and a very popular ICMI strategy, cultural
      renaissance. It was concluded that worthwhile activities were conducted under
      ICMI sponsorship, but that the specific aim of demonstrating community-driven,
      culture-based innovations in a manner suitable for dissemination was achieved
      only to a limited extent. Based on this outcome together with similar
      experiences, recommendations for future initiatives are suggested.

PMID- 22400465
TI  - Evolution of San Francisco Bay Area urban trails.
AB  - The Family and Child Guidance Clinic of the Native American Health Center (NAHC)
      has developed strong working relationships with San Francisco Bay Area system
      partners in order to serve the mental health needs of American Indian/Alaska
      Native children and families. NAHC worked relentlessly with stakeholders to pave
      the Urban Trails that urban Indigenous community members utilize to access
      culturally competent care. These Urban Trails have been grounded in a community
      based system of care model and cultural framework that links substance abuse and
      mental health through a holistic approach congruent with Indigenous values and
      traditions. This article describes how NAHC has partnered with community members
      and organizational stakeholders to develop and sustain an effective holistic
      system for serving urban Indigenous people.

PMID- 22400466
TI  - Design of a behavioral health program for urban American Indian/Alaska Native
      youths: a community informed approach.
AB  - American Indian/Alaska Native (AI/AN) urban youths experience significant mental
      health and substance use problems. However, culturally relevant treatment
      approaches that incorporate community perspectives within the urban setting are
      limited. This study analyzes community perspectives from AI/AN parents, AI/AN
      youths, and services providers within Los Angeles County. Information gathered
      was utilized to develop a needs assessment for AI/AN youths with mental health
      and substance use problems and to design a community-informed treatment approach.
      Nine focus groups and key informant interviews were conducted. The Los Angeles
      County community strongly expressed the need for providing urban AI/AN youths
      with traditional healing services and cultural activities within their treatment
      program. However, various barriers to accessing mental health and substance abuse
      treatment services were identified. An integrated treatment approach was
      subsequently designed as a result of input derived from community perspectives.
      The community believed that providing urban AI/AN youths with an integrated
      treatment approach has the potential to decrease the risk of mental health and
      substance abuse problems in addition to enhancing their cultural identity and
      self esteem.

PMID- 22400467
TI  - The relevance of cultural activities in ethnic identity among California Native
      American youth.
AB  - This study analyzed data from a large statewide sample of Native American
      adolescents throughout California to determine whether participation in cultural
      practices was associated with stronger ethnic identity. The Multigroup Ethnic
      Identity Measure (MEIM) scale was used to measure the ethnic identity of 945
      Native American adolescents (416 male, 529 female) aged 13 - 19 across
      California. Respondents who participated in cultural activities including pow
      wows, sweat lodge, drum group and roundhouse dance reported significantly higher
      Native American ethnic identity than their counterparts who did not take part in
      cultural activities. The association between cultural activities and ethnic
      identity was only significant among urban youth and not among reservation youth.
      Higher grades in school were associated with ethnic identity among females but
      not among males. Findings from this study show a strong association between
      cultural activities and traditional practices with tribal enculturation among
      Native American youth in California. Cultural-based practices to enhance Native
      identity could be useful to improve mental and behavioral health among Native
      American youth.

PMID- 22400468
TI  - Evaluation of a substance abuse, HIV and hepatitis prevention initiative for
      urban Native Americans: the Native Voices program.
AB  - Although many community-based prevention interventions are conducted in American
      Indian and Alaska Native (AI/AN) communities, few studies report the outcomes.
      This article is a mixed methods outcome evaluation of an HIV/AIDS, hepatitis, and
      substance abuse prevention intervention for an urban AI/AN community, Native
      Voices. The study group wascomposed of 100youth (ages 13 to 18) who lived in the
      San Francisco Bay Area. The outcome measures of interest were knowledge,
      perception of risk, sexual self-efficacy, ethnic identity, and sexual risk
      behavior. The findings indicate that knowledge, perception of risk, and sexual
      self-efficacy increased, while no change was shown in measures of ethnic identity
      and behavior. Findings extended prior research by evaluating the Gathering of
      Native Americans (GONA) curriculum, a promising intervention designed for AI/AN
      people.

PMID- 22400469
TI  - Evidence-based practices, attitudes, and beliefs in substance abuse treatment
      programs serving American Indians and Alaska Natives: a qualitative study.
AB  - Substance abuse disproportionately impacts American Indian/Alaska Native (AI/AN)
      communities in the United States. For the increasing numbers of AI/AN individuals
      who enter and receive treatment for their alcohol or other drug problem it is
      imperative that the service they receive be effective. This study used
      qualitative methodology to examine attitudes toward evidence-based practices,
      also known as evidence-based treatments (EBTs) in minority-serving substance
      abuse treatment programs in the San Francisco Bay area. Twenty-two interviews
      were conducted in the study, of which seven were with program directors and
      substance abuse counselors at two urban AI/AN focused sites. These clinics were
      more likely than other minority-focused programs to have experience with research
      and knowledge about adapting EBTs. Only in the AI/AN specific sites did an issue
      arise concerning visibility, that is, undercounting AI/AN people in national and
      state databases. Similar to other minority-focused programs, these clinics
      described mistrust, fear of exploitation from the research community, and
      negative attitudes towards EBTs. The underutilization of EBTs in substance abuse
      programs is prevalent and detrimental to the health of patients who would benefit
      from their use. Future research should explore how to use this research
      involvement and experience with adaptation to increase the adoption of EBTs in
      AI/AN serving clinics.

PMID- 22400470
TI  - [The Essenes and medicine].
AB  - The Essenes were a Jewish sect, which flourished around the first century. We
      have limited our study to hygienic and medical aspects, as documented in the
      works of Josephus Flavius, Philo of Alexandria, and Pliny the Elder; Josephus and
      Philo were personally in contact with these sectarian Jews. We have described the
      regimen of life of these communities, who lived in strictly organised fashion,
      their meals taken in common, their bathing in cold water, their clothing, the
      Sabbath rest, the lavatories, and more. Most Essenes remained single, they
      adopted however small children, and educated them in accordance to their
      principles. There was no private property, but old people and sick residents were
      taken care of by the community. The Essenes, as well as the Therapeuts described
      by Philo, were knowledgeable in medical lore, they treasured old books and
      studied the virtues of medicinal plants. There is no clear-cut consensus whether
      the Essenes, the Therapeuts, and the Qumran residents were one and the same sect,
      or whether they were similar sub-sects. The calm, strictly regulated and frugal
      way of life of the Essenes enabled them to attain old age, often beyond 100
      years.

PMID- 22400471
TI  - [The Anatomy Institutions of Jean Guinter d'Andernach (1487-1574), and Andre
      Vesale (1514-1564). ].
AB  - The text of the Anatomical Institutions of Johann Guinter von Andernach, in its
      original version, was published almost simultaneously in Paris and Basel in 1536.
      Guinter was then in his fiftieth year, and Andreas Vesalius who was his student
      in Paris between 1533 ans 1536, was only twenty-two years old. His studies being
      finished in Leuven and his thesis being published for the first edition in Leuven
      in February 1537, and for the second in Basel in March 1537, Vesalius went to
      Padua where he was named professor of anatomy and surgery. Vesalius, besides the
      reasons put forward in his dedicatory lettre to Johann Armenterianus, tried to
      have rapidly printed documents for his students. He published in this way in
      April 1538 the engraved version of the great plates which he had mostly drawn and
      used to support his demonstrations during sessions of dissection. For the
      accompanying text, he choosed the handbook of his Master Guinter von Andernach
      which he decided to edit incorporating modifications and which he published in
      Venice in 1538 by D. Bernardinus. The modifications made by Vesalius on the
      Guinter's text can be classified in several headings: minor adjustments,
      additions of anatomical comments, additions corroborating traditional physiology,
      and anecdotes peppering the text.

PMID- 22400472
TI  - [The influence of anatomical treaties on the works of Wendel Dietterlin and his
      successors in the second half of the 16th century].
AB  - In 1543 in Basel, Johannes Oporinus published one of the most famous treatises in
      the history of anatomy, De humani corporis fabrica by Andreas Vesalius. The book
      was an immediate success all over Europe, especially in the Upper Rhine region.
      In Strasbourg, Walter Ryff (Gualterius Rivius) was responsible for an early copy;
      others followed, as for example Felix Platter in Basel in 1581. One of the
      novelties of all these books consisted in the fact that for the first time the
      human body was dissected into its smallest units. Anatomical elements such as the
      opened thorax, the vertebral column, the kidney sectionned, or the laryngeal
      cartilages apparently stimulated an artist of the late 16th century in the same
      geographical region: Wendel Dietterlin (c.1550-1599) who principally worked in
      Strasbourg and introduced these elements into his treatise on architecture as
      architectural ornaments. This seems to be the first instance of a transfer of
      motifs from human anatomy to architecture. From this time on, the transfer
      reappeared in some works until William Hogarth's era in the 18th century.

PMID- 22400473
TI  - [Surgical instruments and the emblems of Alsatien craftsmen and the archives of
      Obernai (16th-17th centuries)].
AB  - This study presents some original data concerning the instruments used by
      Alsatian surgeons-barbers from the 16th to the 18th century. Emblems of
      professions frequently appear on private houses in Alsace, and 35 emblems of
      surgeons-barbers have been discovered; six, particularly chararacteristic, are
      analysed here (Soultz 1568, Marlenheim 1581, Sainte-Croix-en-Plaine 1587, Rosheim
      1681, Rosheim 1733, and Wasselonne 1738). The razor (Schermesser), the lancet
      (Lanzette), and the "flame" (Lasseisen, Fliete) are the most frequently
      represented instruments. Unpublished inventories after death also bring
      instructive data and in particular those of the barbers Hans Artz of Molsheim
      (1597) and Jacob Pflieger of Obernai (c. 1608-1609). At last, are evoked
      unpublished mentions concerning two barbers originating from Obernai who
      exercised in Eastern Europe (Sebald Korn around 1583, and Johannes Baur around
      1637).

PMID- 22400474
TI  - [The health of cardinal Gaston de Rohan. The sickness, the diplomat in the noble
      class of the 17th century?].
AB  - The few elements concerning health and medicine discovered during the exhaustive
      study of the numerous documents evoking the Rohan family are presented here. They
      concern essentially Gaston de Rohan (1674-1749). Born in Paris the 27th of June
      1674, son of Francois de Rohan, Prince of Soubise, lieutenant-general of the
      French royal army, and of Anne Julienne de Rohan-Chabot, Gaston de Rohan was
      elected canon of the great-chapter in Strasbourg in 1690, then coadjutor of the
      Prince-bishop of Strasbourg in 1701. He became Prince-bishop of Strasbourg in
      1704 and cardinal in 1712. He died in Paris the 19th of July 1749. The "gout" of
      the cardinal is omnipresent in the life of this man of the Church. Moreover, gout
      imposes upon the life of this statesman, preventing him from going to a given
      place which doesn't fill him with enthusiasm. His gout also allows to impose
      etiquette, since it obliges to go at the cardinal place, who receives. The
      illness becomes non diplomatic, but diplomacy.

PMID- 22400475
TI  - [French faculty of the imperial University of Vilnius in the beginning of the
      19th century].
AB  - Known under the name of Vilna at the beginning of the 19th century, Vilnius
      (today the capital of Lithuania) was then a fast-expanding city, at a crossroads
      of sciences and arts in Europe. The mainspring of this influence was indisputably
      its University, the first in Russia considering the number of students, above
      those of Dorpat (today Tartu) and Moscow. When the University was secularized in
      1773, among the new disciplines introduced, was natural history. It was thus
      decided to create a Collegium medicum. Bishop Massalski, as president of the
      Commission of National Education, put his personal physician, the French Nicolas
      Regnier (1723-1800), a native of Strasbourg, in charge of the creation of this
      school and nominated him in 1775 to the post of professor of anatomy and surgery.
      Nicolas Regnier was thus the first of the seven physicians originating from
      France who marked the expansion of the Faculty of Medicine in Vilnius with
      Jacques Briotet (1746-1819), Jean Emmanuel Gilibert (1741-1814), Auguste Becu
      (1771-1824), Jean Pierre Frank (1745-1821), Joseph Frank (1771-1841), and Louis
      Henri Bojanus (1776-1827).

PMID- 22400476
TI  - [From Paris to Strasbourgh: the development of orthopedic and gymnastic clinics
      (first half of the 19th century)].
AB  - In this contribution, we try to outline a history of the rise of orthopaedic and
      gymnastic clinics from 1820 to 1860 in France, and particularly in Paris. These
      clinics are located at the crossroads of several social processes of the 19th
      century: the structuring of a medical field (observed through specialization,
      professionalization, etc.), physical exercises legitimating process or the
      development of a medical interest for the female body. Several types of interests
      and issues--epistemological, educational, social, professional or symbolic--cross
      around those clinics and place them as major elements in the constitution of a
      history of medical engagement in the production of physical education during the
      nineteenth century. Divided in two parts, our presentation will try to highlight
      various elements of a history of those clinics' rise: their directors, a
      geography of the implantation in Paris and a description of their customers,
      looking at the various educational and rehabilitative methodologies implemented
      in the different clinics.

PMID- 22400477
TI  - [The Chair of the medical chemistry department at the Faculty of Medicine and the
      Chair of chemistry at the School of Pharmacy of Strasbourg (1794-1871)].
AB  - Strasbourg occupied during the 19th century a privileged place in chemistry, as
      well in education as in research, and that in particular in three institutions
      created after the dissolution of the old University during the French Revolution:
      the Faculty of Sciences, the School then Faculty of Medicine created in 1794, and
      the School of Pharmacy created in 1804. In 1871, Alsace was annexed by Germany.
      The chair of medical chemistry in the Faculty of Medicine was successively
      occupied by: Pierre Francois Nicolas (1743-1816) in 1794-1795, Frederic Louis
      Ehrmann (1741-1801) from 1796 to 1798, Gabriel Masuyer (1761-1849) from 1798 to
      1838, and Amedee Cailliot (1805-1884) from 1838 to 1871. The chair of chemistry
      in the School of Pharmacy was successively occupied by: Louis Hecht (1771
      1857)from 1804 to 1835, Jean Francois Persoz (1805-1868) from 1835 to 1852,
      Adrien Loir (1816-1899) from 1852 to 1855, Charles Frederic Gerhardt and Eugene
      Theodore Jacquemin (1828-1909) from 1856 to 1871.

PMID- 22400478
TI  - [Stories of the scientific travels between Strasbourg and Germany in the 19th
      century].
AB  - Appeared in the 19th century, the vogue of the scientific travellings and of the
      medical congresses led numerous physicians to discover the medical institutions
      of European countries. Many Alsatian physicians went to the discovery of the
      medicine and of the hospitals in Germany and central Europa, and then published
      their travel stories. The German physicians were numerous to go to Paris, and
      some of them went through Strasbourg to study the medical institutions. From
      various accounts, the view of physicians from Strasbourg of the Germanic medicine
      and the German view of the medicine in Strasbourg are presented: in both cases,
      these impressions illustrate the role of a bridge between France and Germany
      traditionally played by the Faculty of Medicine in Strasbourg.

PMID- 22400479
TI  - [Japanese students and assistants of the medical faculty of Strasbourg from 1872
      to 1918].
AB  - After the annexation of Alsace by Germany, ratified by the treatise of Versailles
      in January 1871, a new large-scale university was created in Strasbourg by the
      German authorities. It was inaugurated the 1st of May 1872, named Kaiser-Wilhelms
      Universitat from 1877, and existed until the return of Alsace to France in 1918.
      Due to its prestige, this university rapidly attracted foreign students (i.e. nor
      Alsation nor German, representing the majority). Among those, 48 Japanese
      students were registered at the Faculty of Medicine between 1872 and 1918, and
      moreover one assistant, and in particular (by chronological order of first
      registration): Kenji Osawa (1878-1882), Yoshikiyo Koganei (1882-1883), Tsukasa
      Hirota (1885-1888), Masunosuke Hirayama (1889-1890), Trasaburo Araki (1889-1893),
      Tatsukichi Irisawa (1890-1892), Katsutake Azuma (1898-1899), Akira Fujinami (1898
      1899), Toshijiro Chiba (1899-1900), Junichi Mochizuki (1899-1900), Buntaro Adachi
      (1899-1903), Haruo Hayashi (1903-1904), Ryokichi Inada (1904-1905), Takaoki
      Sasaki (1905-1906), Kaoru Aoki (1908-1913), and Jujiro Honda (1910-1911), who had
      then a prestigious universitary career in Japan. Among these 48 students, at
      least 7 realized their dissertation for the doctorate of medicine in Strasbourg
      (Osawa 1882, Maki 1884, Takahashi 1887, Mayeda 1890, Araki 1891, Matsuyama 1898,
      Ito 1899).

PMID- 22400480
TI  - [Strasbourg, capital of mycosis fungoides research from 1919 to 1964].
AB  - Both "Pautrier microabscesses" and "Woringer-Kolopp disease" terms make reference
      to two professors of dermatology of the Faculty of Medicine in Strasbourg. These
      eponyms, and especially that of Pautrier, are universally used by pathologists
      throughout the world. Their origin is amazing. Louis Marie Pautrier (1876-1958)
      is indeed not the father of the microabscesses which are designed by his name.
      This pathognomonic image of mycosisfungoides was in fact described by Jean Darier
      in 1889. It is probably due to the close bonds between Pautrier and his
      colleagues in New York if his name has been attached erroneously for two reasons
      to this histological sign, since abscesses contain by definition
      polymorphonuclear leucocytes and not lymphocytes. Pautrier was between 1919 and
      1958 one of the major French dermatologists having a passion for granulomatoses
      and mycosis fungoides. His student Frederic Woringer (1903-1964) published in
      1939 the clinical case of a mysterious affection, which he had interpreted as a
      case of Paget disease. It is only after his death that this characteristic entity
      has been called Woringer-Kolopp disease. Kolopp was a dermatologist with private
      practice in Metz and addressed the biopsy of the princeps case to Strasbourg.
      This rare affection is considered today as an entity within the spectrum of
      epidermotropic T lymphomas, among which mycosis fungoides is the major entity.

PMID- 22400481
TI  - [Bogdan Suchodolski--initiator and editor-in-chief of the publication History of
      Polish Science].
AB  - Among numerous and distinguished author's and editorial works of Bogdan
      Suchodolski a particular value presents a publication in eight volumes entitled
      'History of Polish Science' (including two biographical and bibliographic
      volumes), which was published in the years 1970-1992 on Professor's own
      initiative and edited by himself. This is the first synthesis of the history of
      science in Poland, from the beginning of the Middle Ages till the present time
      (to 1952). In the conception of the initiator and editor the work presents the
      development of scientific thought and achievements of the scholars in relation to
      national culture and in connexions with the trends in science in the world.
      'History of Polish Science' is the work written by several dozen authors,
      representing different domains of the knowledge. Scientific, organizational and
      editorial patronate was possible by dint of History of Science and Technology
      Establishment of Polish Academy of Sciences (presently the Institute for the
      History of Science of Polish Academy of Sciences), which was managed by Bogdan
      Suchodolski.

PMID- 22400482
TI  - [Outlooks of Bogdan Suchodolski on the issue of popularizing the history of
      science].
AB  - The author of the present article proves the veracity of the postulate, which was
      formulated by Bogdan Suchodolski and concerned the necessity of popularizing the
      history of science. The stipulation is still greatly important for many fields of
      human activity. Bogdan Suchodolski was not the first and the only thinker, who
      revealed the unquestionable significance of disseminating the history of science
      as scientific branch: For the first time the problem was noticed in 1900 during
      International Congress of Comparative History in Paris and in 1903 during
      International Congress of Historical Sciences in Rome, when the idea of
      universalizing the history of science was put forward, among others, by: Paul
      Tannery, Carre de Vaux, Gino Ioria and Karl Sudhoff. All the mentioned
      participants declared then the necessity of teaching the history of science both
      in the secondary schools and in the universities. In the article was also
      included a detailed description of conceptions formulated by Paul Tannery and
      Michel Lheritier in the inter-war period that concerned popularizing the history
      of science, and differed much from each other. Unlike Paul Tannery, Michel
      Lheritier advised against separating history of science from the whole of
      history. On the occasion of describing the inter-war period the author is paying
      a special attention to the role, which was played by International Conference of
      Teaching History in Hague in 1932. In that time a representative of International
      Committee on the History of Sciences and International Academy of the History of
      Sciences--Aldo Mieli--presented the idea of disseminating the history of science,
      which resulted in a resolution saying that the discussed branch should be taught
      in the primary and secondary schools, and in the universities as well. Further,
      the paper includes the description of the detailed conceptions that were put
      forward after World War II by the members of Committee on Teaching within
      International Academy of the History of Science and the participants of
      International Congress of the History of Science in 1965 and in 1968, and
      concerned the idea of introducing compulsory lectures on the history of science
      for prospective teachers and lecturers, and the ways of universalizing the
      discussed branch. The author is also presenting American conceptions of
      popularizing the history of science that were created by George Sarton, Derek J.
      de Solla Price and by Committee on University Education that was established in
      the 1970s. In the article one can find a specific reflection of Bogdan
      Suchodolski on popularizing the history of science through admitting its social
      role, making it the main element of educating 'the modern man' and teaching the
      branch in Poland. The author describes the above-mentioned stipulations in
      detail. At the same time, the last part of the paper reveals Polish thought in
      the field of disseminating the history of science in the inter-war period, so in
      times, when Bogdan Suchodolski was on the point of building his own idea. The
      author makes an attempt at showing to what extent Bogdan Suchodolski was inspired
      by one of the most famous Polish originators and precursors of a new branch
      'science of science'--Florian Znaniecki. On this occasion the author draws
      definite conclusions concerning similarities and differences between the
      conception created by Bogdan Suchodolski, and the ideas that were put forward by
      his predecessor.

PMID- 22400483
TI  - "Showplace of the Cherokee Nation": race and the making of a southern house
      museum.
AB  - This article traces the restoration history of the Chief Vann House State
      Historic Site, a former Cherokee plantation owned and operated by the state of
      Georgia. The article explores the make-up of the restoration community in the
      1950s and identifies aspects of convergence and divergence among this white,
      elite group in terms of both their visions for the site and their notions of how
      best to represent Indians. It argues that restorers used the restoration process
      as a route for personal and community identity enhancement, identifying with the
      storied Cherokee Indians and claiming "Indian" characteristics and the historical
      experience of Indian removal for themselves.

PMID- 22400484
TI  - Relies of reconciliation: the Confederate Museum and Civil War memory in the New
      South.
AB  - This article examines the Confederate Memorial Literary Society (CMLS), an
      organization of elite white women in Richmond, Virginia who founded the
      Confederate Museum in the 1890s. Faced with the plunder of Civil War relics and
      cultural homogenization on northern terms, the CMLS founded the Confederate
      Museum to document and defend the Confederate cause and to uphold the antebellum
      mores that the New South's business ethos threatened to erode. In the end,
      however, the museum's version of the Lost Cause served the New South. By focusing
      on military sacrifice, the Confederate Museum aided the process of sectional
      reconciliation. By depicting slavery as benevolent, the museum's exhibits
      reinforced the notion that Jim Crow was a just and effective means of managing
      postwar southern society. Lastly, by glorifying the common soldier and portraying
      the South as "solid," the museum promoted obedience to the mandates of industrial
      capitalism. Thus, the Confederate Museum both critiqued and eased the economic
      transformations of the New South.

PMID- 22400485
TI  - Petalonia binghamiae extract and its constituent fucoxanthin ameliorate high-fat
      diet-induced obesity by activating AMP-activated protein kinase.
AB  - In this study, we investigated the antiobesity properties of  Petalonia
      binghamiae  extract (PBE) in mice in which obesity was induced with a high-fat
      diet (HFD). PBE administration (150 mg/kg/day) for 70 days decreased body weight
      gain, adipose tissue weight, and the serum triglyceride level in mice fed a HFD.
      PBE reduced serum levels of glutamic pyruvic transaminase and glutamic
      oxaloacetic transaminase as well as the accumulation of lipid droplets in the
      liver. PBE restored the HFD-induced decrease in phosphorylation of AMP-activated
      protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in epididymal adipose
      tissue. PBE increased the phosphorylation of AMPK and ACC and decreased the
      expression of SREBP1c in mature 3T3-L1 adipocytes. In addition, we further
      explored the active compound responsible for AMPK activation by PBE in 3T3-L1
      adipocytes. Fucoxanthin isolated from PBE increased the phosphorylation of AMPK
      and ACC with increasing LKB1 phosphorylation in mature 3T3-L1 adipocytes. Taken
      together, these data suggest that PBE (or fucoxanthin) exert improving effects on
      HFD-induced obesity by promoting beta-oxidation and reducing lipogenesis.

PMID- 22400486
TI  - Switchable induced polarization in LaAlO3/SrTiO3 heterostructures.
AB  - Demonstration of a tunable conductivity of the LaAlO(3)/SrTiO(3) interfaces drew
      significant attention to the development of oxide electronic structures where
      electronic confinement can be reduced to the nanometer range. While the
      mechanisms for the conductivity modulation are quite different and include metal
      insulator phase transition and surface charge writing, generally it is implied
      that this effect is a result of electrical modification of the LaAlO(3) surface
      (either due to electrochemical dissociation of surface adsorbates or free charge
      deposition) leading to the change in the two-dimensional electron gas (2DEG)
      density at the LaAlO(3)/SrTiO(3) (LAO/STO) interface. In this paper, using
      piezoresponse force microscopy we demonstrate a switchable electromechanical
      response of the LAO overlayer, which we attribute to the motion of oxygen
      vacancies through the LAO layer thickness. These electrically induced reversible
      changes in bulk stoichiometry of the LAO layer are a signature of a possible
      additional mechanism for nanoscale oxide 2DEG control on LAO/STO interfaces.

PMID- 22400487
TI  - Luminescent iridium(III) complexes with N^C^N-coordinated terdentate ligands:
      dual tuning of the emission energy and application to organic light-emitting
      devices.
AB  - A family of complexes (1a-3a and 1b-3b) was prepared, having the structure
      Ir(N^C^N)(N^C)Cl. Here, N^C(?)N represents a terdentate, cyclometallating ligand
      derived from 1,3-di(2-pyridyl)benzene incorporating CH(3) (1a,b), F (2a,b), or
      CF(3) (3a,b) substituents at the 4 and 6 positions of the benzene ring, and N^C
      is 2-phenylpyridine (series a) or 2-(2,4-difluorophenyl)pyridine (series b). The
      complexes are formed using a stepwise procedure that relies on the initial
      introduction of the terdentate ligand to form a dichloro-bridged iridium dimer,
      followed by cleavage with the N^C ligand. (1)H NMR spectroscopy reveals that the
      isomer that is exclusively formed in each case is that in which the pyridyl ring
      of the N^C ligand is trans to the cyclometallating aryl ring of the N^C^N ligand.
      This conclusion is unequivocally confirmed by X-ray diffraction analysis for two
      of the complexes (1b and 3a). All of the complexes are highly luminescent in
      degassed solution at room temperature, emitting in the green (1a,b), blue-green
      (2a,b), and orange-red (3a,b) regions. The bidentate ligand offers independent
      fine-tuning of the emission energy: for each pair, the "b" complex is blue
      shifted relative to the analogous "a" complex. These trends in the excited-state
      energies are rationalized in terms of the relative magnitudes of the effects of
      the substituents on the highest occupied and lowest unoccupied orbitals,
      convincingly supported by time-dependent density functional theory (TD-DFT)
      calculations. Luminescence quantum yields are high, up to 0.7 in solution and
      close to unity in a PMMA matrix for the green-emitting complexes. Organic light
      emitting devices (OLEDs) employing this family of complexes as phosphorescent
      emitters have been prepared. They display high efficiencies, at least comparable,
      and in some cases superior, to similar devices using the well-known tris
      bidentate complexes such as fac-Ir(ppy)(3). The combination of terdentate and
      bidentate ligands is seen to offer a versatile approach to tuning of the
      photophysical properties of iridium-based emitters for such applications.

PMID- 22400488
TI  - Adrenomedullin expression in epithelial ovarian cancers and promotes HO8910 cell
      migration associated with upregulating integrin alpha5beta1 and phosphorylating
      FAK and paxillin.
AB  - BACKGROUND: Epithelial ovarian cancer (EOC) is one of the leading causes of
      cancer deaths in women worldwide. Adrenomedullin (AM) is a multifunctional
      peptide which presents in various kinds of tumors. METHODS: In this study, we
      characterized the expression and function of AM in epithelial ovarian cancer
      using immunohistochemistry staining. Exogenous AM and small interfering RNA
      (siRNA) specific for AM receptor CRLR were treated to EOC cell line HO8910. Wound
      healing assay and flow cytometry were used to measure the migration ability and
      expression of integrin alpha5 of HO8910 cells after above treatments. Western
      blot was used to examine the phosphorylation of FAK and paxillin. RESULTS: We
      found that patients with high AM expression showed a higher incidence of
      metastasis, larger residual size of tumors after cytoreduction and shorter
      disease-free and overall survival time. Exogenous AM induced ovarian cancer cell
      migration in time- and dose- dependent manners. AM upregulated the expression of
      integrin alpha5 and phosphorylation of FAK, paxillin as well. CONCLUSIONS: Our
      results suggested that AM contributed to the progression of EOC and had
      additional roles in EOC cell migration by activating the integrin alpha5beta1
      signaling pathway. Therefore, we presumed that AM could be a potential molecular
      therapeutic target for ovarian carcinoma.

PMID- 22400489
TI  - Symmetrical peripheral gangrene in four pediatric cardiac surgery patients
      receiving extracorporeal membrane oxygenation.
AB  - Symmetrical peripheral gangrene (multilimb ischemia without large artery
      occlusion) is a rare condition usually associated with disseminated intravascular
      coagulation, hemodynamic compromise, and/or sepsis. However, it has not been
      described in patients on extracorporal membrane oxygenation (ECMO). Over a 5 year
      period, four pediatric patients developed symmetrical peripheral gangrene on ECMO
      after cardiac surgery. They subsequently died and came to autopsy. History,
      physical examination, and laboratory studies were examined. Gross and microscopic
      autopsy material was reviewed. Patients were 11 days to 13 years old.
      Extracorporal membrane oxygenation duration was 11-22 days, and limb ischemia
      began 2-4 days before death. Three patients had rapid onset, with ischemia
      developing in <48 hours. In the fourth, ischemic changes began as focal lesions
      and gradually spread. Two patients were septic. Three had evidence of other end
      organ damage. Pressors were used in 3 patients before the limb ischemia.
      Autopsies disclosed ischemic changes involving all limbs, with confluent
      ecchymoses. In a detailed examination in 1 case, large arteries of the
      extremities were patent. Involved skin and soft tissue showed bland fibrin
      thrombi in the microcirculation, with tissue necrosis and hemorrhage. This report
      describes the first 4 cases of symmetrical peripheral gangrene complicating ECMO.
      The 4 pediatric patients all had recent surgery for congenital cardiac disease,
      and all had significant exposure to ECMO prior to developing limb ischemia.
      Symmetrical peripheral gangrene is an unusual complication of ECMO that may arise
      in the setting of disseminated intravascular coagulation, sepsis, or other
      hemostatic and/or hemodynamic imbalance.

PMID- 22400490
TI  - Competitive activity-based protein profiling identifies aza-beta-lactams as a
      versatile chemotype for serine hydrolase inhibition.
AB  - Serine hydrolases are one of the largest and most diverse enzyme classes in
      Nature. Most serine hydrolases lack selective inhibitors, which are valuable
      probes for assigning functions to these enzymes. We recently discovered a set of
      aza-beta-lactams (ABLs) that act as potent and selective inhibitors of the
      mammalian serine hydrolase protein-phosphatase methylesterase-1 (PME-1). The ABLs
      inactivate PME-1 by covalent acylation of the enzyme's serine nucleophile,
      suggesting that they could offer a general scaffold for serine hydrolase
      inhibitor discovery. Here, we have tested this hypothesis by screening ABLs more
      broadly against cell and tissue proteomes by competitive activity-based protein
      profiling (ABPP), leading to the discovery of lead inhibitors for several serine
      hydrolases, including the uncharacterized enzyme alpha,beta-hydrolase domain
      containing 10 (ABHD10). ABPP-guided medicinal chemistry yielded a compound ABL303
      that potently (IC(50) ~ 30 nM) and selectively inactivated ABHD10 in vitro and in
      living cells. A comparison of optimized inhibitors for PME-1 and ABHD10 indicates
      that modest structural changes that alter steric bulk can tailor the ABL to
      selectively react with distinct, distantly related serine hydrolases. Our
      findings, taken together, designate the ABL as a versatile reactive group for
      creating first-in-class serine hydrolase inhibitors.

PMID- 22400491
TI  - Fluoroquinolone resistance in uncomplicated acute pyelonephritis: epidemiology
      and clinical impact.
AB  - The objectives of this study were to investigate antibiotic resistance in urinary
      pathogens from Korean patients with uncomplicated acute pyelonephritis (UAPN),
      and to determine the effect of fluoroquinolone (FQ) resistance on clinical
      outcome in those patients with UAPN initially treated with FQ. Clinical and
      microbiologic data for all the APN patients attending 14 hospitals in South Korea
      in 2008 were collected retrospectively. Urinary pathogens were identified in 719
      cases, and Escherichia coli was the most common pathogen (661/719, 91.9%).
      Antibiotic susceptibilities to several E. coli antibiotics were as follows:
      ciprofloxacin, 84.1%; trimethoprim-sulfamethoxazola (TMP-SMX), 67.2%; and
      extended-spectrum beta-lactamase-negative, 92.4%. FQ was the most frequent
      antibiotic prescribed for UAPN (45.3% intravenously and 53.9% by mouth). We
      compared clinical outcomes and hospital days in patients with FQ-resistant (32)
      and FQ-sensitive E. coli (173) who received FQ as initial empirical therapy.
      Clinical cure was higher in the FQ-sensitive group (78% vs. 91%, p=0.027), and
      hospital days were longer in the FQ-resistant group (9.6+/-5.5 days vs. 7+/-3.5
      days, p=0.001). In conclusion, FQ-sensitivity of E. coli from UAPN was 84.1%. FQ
      treatment of UAPN caused by FQ-resistant E. coli has a lower cure rate and
      involves longer hospital stay than FQ treatment of cases caused by FQ-sensitive
      E. coli.

PMID- 22400492
TI  - Metabolic cytometry: capillary electrophoresis with two-color fluorescence
      detection for the simultaneous study of two glycosphingolipid metabolic pathways
      in single primary neurons.
AB  - Metabolic cytometry is a form of chemical cytometry wherein metabolic cascades
      are monitored in single cells. We report the first example of metabolic cytometry
      where two different metabolic pathways are simultaneously monitored. Glycolipid
      catabolism in primary rat cerebella neurons was probed by incubation with
      tetramethylrhodamine-labeled GM1 (GM1-TMR). Simultaneously, both catabolism and
      anabolism were probed by coincubation with BODIPY-FL labeled LacCer (LacCer
      BODIPY-FL). In a metabolic cytometry experiment, single cells were incubated with
      substrate, washed, aspirated into a capillary, and lysed. The components were
      separated by capillary electrophoresis equipped with a two-spectral channel laser
      induced fluorescence detector. One channel monitored fluorescence generated by
      the metabolic products produced from GM1-TMR and the other monitored the
      metabolic products produced from LacCer-BODIPY-FL. The metabolic products were
      identified by comparison with the mobility of a set of standards. The detection
      system produced at least 6 orders of magnitude dynamic range in each spectral
      channel with negligible spectral crosstalk. Detection limits were 1 zmol for
      BODIPY-FL and 500 ymol for tetramethylrhodamine standard solutions.

PMID- 22400493
TI  - A pathological fracture and a solitary mass in the right clavicle: an unusual
      first presentation of HCC and the role of immunohistochemistry.
AB  - Hepatocellular carcinoma (HCC) is an aggressive malignant tumor that occurs
      throughout the world. MUetastases from hepatocellular carcinoma (HCC) were
      generally considered to be rare in the past, because the carcinoma had an
      aggressive clinical course. In our era, has been reported that extra-hepatic
      metastases occur in 13.5%-41.7% of HCC patients and this is considered as
      terminal-stage cancer. The prognosis for patients at this stage continues to be
      poor due to limited effective treatment. The common sites of extrahepatic
      metastases in patients with HCC are the lungs, regional lymph nodes, kidney, bone
      marrow and adrenals. We present here an extremely infrequent case of a patient,
      without known liver disease, in which the presenting symptom was a pathological
      in retrospect-fracture of his right clavicle which wasn't properly evaluated,
      until he presented a bulky mass in the region 6 months later. For our patient,
      the added diagnostic difficulty alongside the unknown liver disease, has been
      that the clavicular metastases was the first presentation of any metastatic
      disease, rather than the more common sites of HCC spread to adjacent lung or
      lymph nodes.

PMID- 22400494
TI  - Potential association between frequent nonsynonymous variant of NPPA and
      cardioembolic stroke.
AB  - Atrial natriuretic peptide (ANP, also known as NPPA) and brain natriuretic
      peptide (BNP, also known as NPPB) have been determined as genetic factors for
      several diseases, including stroke and myocardial infarction, in human and rat
      models. To investigate the potential association between polymorphisms of the
      NPPA gene and stroke in a Korean population, nine single-nucleotide polymorphisms
      (SNPs) of NPPA and NPPB genes were genotyped in a total of 941 Korean subjects,
      including 674 stroke patients (109 hemorrhagic and 565 ischemic) and 267
      unaffected controls. Genotype comparisons of the targeted alleles revealed that
      there were no significant associations between stroke patients and control
      subjects, or among hemorrhagic, ischemic, and control groups. However, in
      logistic analysis for Trial of Org 10172 in Acute Stroke Treatment (TOAST)
      classification of ischemic stroke, nonsynonymous rs5065 (STOP152Arg) and rs5067
      in 3'UTR of NPPA, which were in complete linkage disequilibrium, showed
      significant associations with cardioembolic stroke. These two SNPs showed higher
      frequencies in cardioembolic stroke patients than those in controls and ischemic
      patients with small-vessel occlusion (p=0.002, adjusted p=0.02). It was also
      found that NPPA rs5065C allele in all of the Korean subjects existed as
      heterozygous compared with Caucasian and African populations. Although further
      replications in larger cardioembolic stroke subjects are required, our
      preliminary findings suggest that the nonsynonymous rs5065C of the NPPA gene,
      which could produce a new or dysfunctional transcript, is possibly associated
      with cardioembolism.

PMID- 22400496
TI  - Secondary metabolites from Marchantia paleacea calluses and their allelopathic
      effects on Arabidopsis seed growth.
AB  - Rapid-growth Marchantia paleacea calluses were induced on MSK2 medium through
      surface sterilisation of the capsula. Ten known compounds including two steroids
      (1-2), six bibenzyls (3, 5-9), a flavonoid (10), and a terpenoid (4) were
      isolated from these calluses. The allelopathic effect of the six bibenzyls was
      assessed in Arabidopsis thaliana. Results revealed that bibenzyls could inhibit
      seedling growth in a dose-dependent manner.

PMID- 22400495
TI  - The extracytoplasmic function sigma factor SigY is important for efficient
      maintenance of the Spbeta prophage that encodes sublancin in Bacillus subtilis.
AB  - Many strains of the soil bacterium Bacillus subtilis are capable of producing and
      being resistant to the antibiotic sublancin because they harbor the Spbeta
      prophage. This 135 kb viral genome is integrated into the circular DNA chromosome
      of B. subtilis, and contains genes for the production of and resistance to
      sublancin. We investigated the role of SigY in sublancin production and
      resistance, finding that it is important for efficient maintenance of the Spbeta
      prophage. We were unable to detect the prophage in mutants lacking SigY.
      Additionally, these mutants were no longer able to produce sublancin, were
      sensitive to killing by this factor, and displayed a delay in sporulation. Wild
      type cells with normal SigY activity were found to partially lose the Spbeta
      prophage during growth and early sporulation, suggesting a mechanism for the
      bistable outcome of sibling cells capable of killing and of being killed. The
      appropriate regulation of SigY appears to be essential for growth as evidenced by
      the inability to disrupt the gene for its putative antisigma. Our results confirm
      a role for SigY in antibiotic production and resistance, as has been found for
      other members of the extracytoplasmic function sigma factor family in B.
      subtilis, and shows that this role is achieved by affecting maintenance of the
      Spbeta prophage.

PMID- 22400497
TI  - Phase transitions in wave turbulence.
AB  - We consider turbulence within the Gross-Pitaevsky model and look into the
      creation of a coherent condensate via an inverse cascade originating at small
      scales. The growth of the condensate leads to a spontaneous breakdown of
      statistical symmetries of overcondensate fluctuations: First, isotropy is broken,
      then a series of phase transitions marks the changing symmetry from twofold to
      threefold to fourfold. We describe respective anisotropic flux flows in the k
      space. At the highest level reached, we observe a short-range positional and long
      range orientational order (as in a hexatic phase). In other words, the more one
      pumps the system, the more ordered the system becomes. The phase transitions
      happen when the system is pumped by an instability term and does not occur when
      pumped by a random force. We thus demonstrate nonuniversality of an inverse
      cascade turbulence with respect to the nature of small-scale forcing.

PMID- 22400498
TI  - Difference of energy density of states in the Wang-Landau algorithm.
AB  - Paying attention to the difference of density of states, Deltaln g(E)=ln
      g(E+DeltaE)-lng(E), we study the convergence of the Wang-Landau method. We show
      that this quantity is a good estimator to discuss the errors of convergence and
      refer to the 1/t algorithm. We also examine the behavior of the first-order
      transition with this difference of density of states in connection with Maxwell's
      equal area rule. A general procedure to judge the order of transition is given.

PMID- 22400499
TI  - Brownian needle in dire straits: stochastic motion of a rod in very confined
      narrow domains.
AB  - We study the mean turnaround time of a Brownian needle in a narrow planar strip.
      When the needle is only slightly shorter than the width of the strip, the
      computation becomes a nonstandard narrow escape problem. We develop a boundary
      layer method, based on a conformal mapping of cusplike narrow straits, to obtain
      an explicit asymptotic approximation to the mean turnaround time. Our result
      suggests that two-dimensional domains lying between parallel walls may play a
      significant role in DNA repair.

PMID- 22400500
TI  - Optimal low symmetric dissipation Carnot engines and refrigerators.
AB  - A unified optimization criterion for Carnot engines and refrigerators is
      proposed. It consists of maximizing the product of the heat absorbed by the
      working system times the efficiency per unit time of the device, either the
      engine or the refrigerator. This criterion can be applied to both low symmetric
      dissipation Carnot engines and refrigerators. For engines the criterion coincides
      with the maximum power criterion and then the Curzon-Ahlborn efficiency eta(CA)=1
      ?T(c)/T(h) is recovered, where T(h) and T(c) are the temperatures of the hot and
      cold reservoirs, respectively [Esposito, Kawai, Lindenberg, and Van den Broeck,
      Phys. Rev. Lett. 105, 150603 (2010)]. For refrigerators the criterion provides
      the counterpart of Curzon-Ahlborn efficiency for refrigerators epsilon(CA)=[1/(?1
      (T(c)/T(h))]-1, first derived by Yan and Chen for the particular case of an
      endoreversible Carnot-type refrigerator with linear (Newtonian) finite heat
      transfer laws [Yan and Chen, J. Phys. D: Appl. Phys. 23, 136 (1990)].

PMID- 22400501
TI  - Cooperative rectification in confined Brownian ratchets.
AB  - We analyze the rectified motion of a Brownian particle in a confined environment.
      We show the emergence of strong cooperativity between the inherent rectification
      of the ratchet mechanism and the entropic bias of the fluctuations caused by
      spatial confinement. Net particle transport may develop even in situations where
      separately the ratchet and the geometric restrictions do not give rise to
      particle motion. The combined rectification effects can lead to bidirectional
      transport depending on particle size, resulting in a different route for
      segregation. The reported mechanism can be used to control transport in
      mesostructures and nanodevices in which particles move in a reduced space.

PMID- 22400502
TI  - Relevance of numerical simulations to booming sand.
AB  - We have performed a simulation study of three-dimensional cohesionless granular
      flows down an inclined chute. We find that the oscillations observed in [L. E.
      Silbert, Phys. Rev. Lett. 94, 098002 (2005)] near the angle of repose are
      harmonic vibrations of the lowest normal mode. Their frequencies depend on the
      contact stiffness as well as on the depth of the flow. Could these oscillations
      account for the phenomena of "booming sand"? We estimate an effective contact
      stiffness from the Hertz law, but this leads to frequencies that are several
      times higher than observed. However, the Hertz law also predicts
      interpenetrations of a few nanometers, indicating that the oscillations
      frequencies are governed by the surface stiffness, which can be much lower than
      the bulk one. This is in agreement with previous studies ascribing the ability to
      sing to the presence of a soft coating on the grain surface.

PMID- 22400503
TI  - Universal fluctuations in Kardar-Parisi-Zhang growth on one-dimensional flat
      substrates.
AB  - We present a numerical study of the evolution of height distributions (HDs)
      obtained in interface growth models belonging to the Kardar-Parisi-Zhang (KPZ)
      universality class. The growth is done on an initially flat substrate. The HDs
      obtained for all investigated models are very well fitted by the theoretically
      predicted Gaussian orthogonal ensemble (GOE) distribution. The first cumulant has
      a shift that vanishes as t(-1/3), while the cumulants of order 2<=n<=4 converge
      to GOE as t(-2/3) or faster, behaviors previously observed in other KPZ systems.
      These results yield evidences for the universality of the GOE distribution in KPZ
      growth on flat substrates. Finally, we further show that the surfaces are
      described by the Airy(1) process.

PMID- 22400504
TI  - Relations between the diffusion anomaly and cooperative rearranging regions in a
      hydrophobically nanoconfined water monolayer.
AB  - We simulate liquid water between hydrophobic walls, separated by 0.5 nm, to study
      how the diffusion constant D(?) parallel to the walls depends on the microscopic
      structure of water. At low temperature T, water diffusion can be associated with
      the number of defects in the hydrogen bond network. However, the number of
      defects solely does not account for the peculiar diffusion of water, with maxima
      and minima along isotherms. Here, we calculate a relation that quantitatively
      reproduces the behavior of D(?), focusing on the high-T regime. We clarify how
      the interplay between breaking of hydrogen bonds and cooperative rearranging
      regions of 1-nm size gives rise to the diffusion extrema in nanoconfined water.

PMID- 22400505
TI  - Statistical mechanics model of angiogenic tumor growth.
AB  - We examine a lattice model of tumor growth where the survival of tumor cells
      depends on the supplied nutrients. When such a supply is random, the extinction
      of tumors belongs to the directed percolation universality class. However, when
      the supply is correlated with the distribution of tumor cells, which as we
      suggest might mimic the angiogenic growth, the extinction shows different
      critical behavior. Such a correlation affects also the morphology of the growing
      tumors and drastically raises tumor-survival probability.

PMID- 22400506
TI  - Driven Brownian transport through arrays of symmetric obstacles.
AB  - We numerically investigate the transport of a suspended overdamped Brownian
      particle which is driven through a two-dimensional rectangular array of circular
      obstacles with finite radius. Two limiting cases are considered in detail,
      namely, when the constant drive is parallel to the principal or the diagonal
      array axes. This corresponds to studying the Brownian transport in periodic
      channels with reflecting walls of different topologies. The mobility and
      diffusivity of the transported particles in such channels are determined as
      functions of the drive and the array geometric parameters. Prominent transport
      features, like negative differential mobilities, excess diffusion peaks, and
      unconventional asymptotic behaviors, are explained in terms of two distinct
      lengths, the size of single obstacles (trapping length), and the lattice constant
      of the array (local correlation length). Local correlation effects are further
      analyzed by continuously rotating the drive between the two limiting
      orientations.

PMID- 22400507
TI  - Static point-to-set correlations in glass-forming liquids.
AB  - We analyze static point-to-set correlations in glass-forming liquids. The generic
      idea is to freeze the position of a set of particles in an equilibrium
      configuration and to perform sampling in the presence of this additional
      constraint. Qualitatively different geometries for the confining set of particles
      are considered and a detailed comparison of resulting static and dynamic
      correlation functions is performed. Our results reveal the existence of static
      spatial correlations not detected by conventional two-body correlators, which
      appear to be decoupled from, and shorter-ranged than, dynamical length scales
      characterizing dynamic heterogeneity. We find that the dynamics slows down
      dramatically under confinement, which suggests new ways to investigate the glass
      transition. Our results indicate that the geometry in which particles are
      randomly pinned is the best candidate to study static correlations.

PMID- 22400508
TI  - Excluded-volume effects in the diffusion of hard spheres.
AB  - Excluded-volume effects can play an important role in determining transport
      properties in diffusion of particles. Here, the diffusion of finite-sized hard
      core interacting particles in two or three dimensions is considered
      systematically using the method of matched asymptotic expansions. The result is a
      nonlinear diffusion equation for the one-particle distribution function, with
      excluded-volume effects enhancing the overall collective diffusion rate. An
      expression for the effective (collective) diffusion coefficient is obtained.
      Stochastic simulations of the full particle system are shown to compare well with
      the solution of this equation for two examples.

PMID- 22400509
TI  - Role of the superposition principle for enhancing the efficiency of the quantum
      mechanical Carnot engine.
AB  - The role of the superposition principle is discussed for the quantum-mechanical
      Carnot engine introduced by Bender, Brody, and Meister [J. Phys. A 33, 4427
      (2000)]. It is shown that the efficiency of the engine can be enhanced by the
      superposition of quantum states. A finite-time process is also discussed and the
      condition of the maximum power output is presented. Interestingly, the efficiency
      at the maximum power is lower than that without superposition.

PMID- 22400510
TI  - Nonstationary heat conduction in one-dimensional models with substrate potential.
AB  - The paper investigates nonstationary heat conduction in one-dimensional models
      with substrate potential. To establish universal characteristic properties of the
      process, we explore three different models: Frenkel-Kontorova (FK), phi4+
      (phi(4)+), and phi4- (phi(4)-). Direct numeric simulations reveal in all these
      models a crossover from oscillatory decay of short-wave perturbations of the
      temperature field to smooth diffusive decay of the long-wave perturbations. Such
      behavior is inconsistent with the parabolic Fourier equation of heat conduction
      and clearly demonstrates the necessity for hyperbolic corrections in the
      phenomenological description of the heat conduction process. The crossover
      wavelength decreases with an increase in the average temperature. The decay
      patterns of the temperature field almost do not depend on the amplitude of the
      perturbations, so the use of linear evolution equations for the temperature field
      is justified. In all models investigated, the relaxation of thermal perturbations
      is exponential, contrary to a linear chain, where it follows a power law. The
      most popular lowest-order hyperbolic generalization of the Fourier law, known as
      the Cattaneo-Vernotte or telegraph equation, is also not valid for the
      description of the observed behavior of the models with the substrate potential,
      since the characteristic relaxation time in an oscillatory regime strongly
      depends on the excitation wavelength. For some of the models, this dependence
      seems to obey a simple scaling law.

PMID- 22400511
TI  - Random walks in modular scale-free networks with multiple traps.
AB  - Extensive empirical investigation has shown that a plethora of real networks
      synchronously exhibit scale-free and modular structure and it is thus of great
      importance to uncover the effects of these two striking properties on various
      dynamical processes occurring on such networks. In this paper, we examine two
      cases of random walks performed on a class of modular scale-free networks with
      multiple traps located at several given nodes. We first derive a formula of the
      mean first-passage time (MFPT) for a general network, which is the mean of the
      expected time to absorption originating from a specific node, averaged over all
      nontrap starting nodes. Although the computation is complex, the expression of
      the formula is exact; moreover, the computational approach and procedure are
      independent of the number and position of the traps. We then determine
      analytically the MFPT for the two random walks being considered. The obtained
      analytical results are in complete agreement with the numerical ones. Our results
      show that the number and location of traps play an important role in the behavior
      of the MFPT, since for both cases the MFPT grows as a power-law function of the
      number of nodes, but their exponents are quite different. We demonstrate that the
      root of the difference in the behavior of MFPT is attributed to the modular and
      scale-free topologies of the networks. This work can deepen the understanding of
      diffusion on networks with modular and scale-free architecture and motivate
      relevant studies for random walks running on complex random networks with
      multiple traps.

PMID- 22400512
TI  - Single-layer metal-on-metal islands driven by strong time-dependent forces.
AB  - Nonlinear transport properties of single-layer metal-on-metal islands driven with
      strong static and time-dependent forces are studied. We apply a semiempirical
      lattice model and use master-equation and kinetic Monte Carlo simulation methods
      to compute observables such as the velocity and the diffusion coefficient. Two
      types of time-dependent driving are considered: a pulsed rotated field and an
      alternating field with a zero net force (electrophoretic ratchet). Small islands
      up to 12 atoms were studied in detail with the master-equation method and larger
      ones with simulations. Results are presented mainly for a parametrization of Cu
      on Cu(001) surface, which has been the main system of interest in several
      previous studies. The main results are that the pulsed field can increase the
      current in both diagonal and axis direction when compared to static field, and
      there exists a current inversion in the electrophoretic ratchet. Both of these
      phenomena are a consequence of the coupling of the internal dynamics of the
      island with its transport. In addition to the previously discovered "magic
      size"effect for islands in equilibrium, a strong odd-even effect was found for
      islands driven far out of equilibrium. Master-equation computations revealed
      nonmonotonous behavior for the leading relaxation constant and effective
      Arrhenius parameters. Using cycle optimization methods, typical island transport
      mechanisms are identified for small islands.

PMID- 22400513
TI  - Percolation of aligned rigid rods on two-dimensional square lattices.
AB  - The percolation behavior of aligned rigid rods of length k (kmers) on two
      dimensional square lattices has been studied by numerical simulations and finite
      size scaling analysis. The kmers, containing k identical units (each one
      occupying a lattice site), were irreversibly deposited along one of the
      directions of the lattice. The process was monitored by following the probability
      R(L,k)(p) that a lattice composed of L*L sites percolates at a concentration p of
      sites occupied by particles of size k. The results, obtained for k ranging from 1
      to 14, show that (i) the percolation threshold exhibits a decreasing function
      when it is plotted as a function of the kmer size; (ii) for any value of k (k>1),
      the percolation threshold is higher for aligned rods than for rods isotropically
      deposited; (iii) the phase transition occurring in the system belongs to the
      standard random percolation universality class regardless of the value of k
      considered; and (iv) in the case of aligned kmers, the intersection points of the
      curves of R(L,k)(p) for different system sizes exhibit nonuniversal critical
      behavior, varying continuously with changes in the kmer size. This behavior is
      completely different to that observed for the isotropic case, where the crossing
      point of the curves of R(L,k)(p) do not modify their numerical value as k is
      increased.

PMID- 22400514
TI  - Directed random walks on hierarchical trees with continuous branching: a
      renormalization group approach.
AB  - We investigate the directed random walk on hierarchic trees. Two cases are
      investigated: random variables on deterministic trees with a continuous
      branching, and random variables on the trees constructed through the random
      branching process. We derive renormalization group (partial differential)
      equations for the branching models with binomial, Poisson, and compound Poisson
      distributions of random variables on the links of a tree. These renormalization
      group equations are a new class of reaction-diffusion equations in one dimension.

PMID- 22400515
TI  - Entropy production and equilibration in Yang-Mills quantum mechanics.
AB  - The Husimi distribution provides for a coarse-grained representation of the phase
      space distribution of a quantum system, which may be used to track the growth of
      entropy of the system. We present a general and systematic method of solving the
      Husimi equation of motion for an isolated quantum system, and we construct a
      coarse-grained Hamiltonian whose expectation value is exactly conserved. As an
      application, we numerically solve the Husimi equation of motion for two
      dimensional Yang-Mills quantum mechanics (the x-y model) and calculate the time
      evolution of the coarse-grained entropy of a highly excited state. We show that
      the coarse-grained entropy saturates to a value that coincides with the
      microcanonical entropy corresponding to the energy of the system.

PMID- 22400516
TI  - Critical short-time dynamics in a system with interacting static and diffusive
      populations.
AB  - We study the critical short-time dynamical behavior of a one-dimensional model
      where diffusive individuals can infect a static population upon contact. The
      model presents an absorbing phase transition from an active to an inactive state.
      Previous calculations of the critical exponents based on quasistationary
      quantities have indicated an unusual crossover from the directed percolation to
      the diffusive contact process universality classes. Here we show that the
      critical exponents governing the slow short-time dynamic evolution of several
      relevant quantities, including the order parameter, its relative fluctuations,
      and correlation function, reinforce the lack of universality in this model.
      Accurate estimates show that the critical exponents are distinct in the regimes
      of low and high recovery rates.

PMID- 22400517
TI  - Quantum and classical fluctuation theorems from a decoherent histories, open
      system analysis.
AB  - In this paper we present a first-principles analysis of the nonequilibrium work
      distribution and the free energy difference of a quantum system interacting with
      a general environment (with arbitrary spectral density and for all temperatures)
      based on a well-understood microphysics (quantum Brownian motion) model under the
      conditions stipulated by the Jarzynski equality [Jarzynski, Phys. Rev. Lett. 78,
      2690 (1997)] and Crooks' fluctuation theorem [Crooks, Phys. Rev. E 60, 2721
      (1999)] (in short, fluctuation theorems, FTs). We use the decoherent histories
      conceptual framework to explain how the notion of trajectories in a quantum
      system can be made viable and use the environment-induced decoherence scheme to
      assess the strength of noise that could provide sufficient decoherence to warrant
      the use of trajectories to define work in open quantum systems. From the
      solutions to the Langevin equation governing the stochastic dynamics of such
      systems we were able to produce formal expressions for these quantities entering
      in the FTs and from them prove explicitly the validity of the FTs at the high
      temperature limit. At low temperatures our general results would enable one to
      identify the range of parameters where FTs may not hold or need be expressed
      differently. We explain the relation between classical and quantum FTs and the
      advantage of this microphysics open-system approach over the phenomenological
      modeling and energy-level calculations for substitute closed quantum systems.

PMID- 22400518
TI  - Mean-field calculation of critical parameters and log-periodic characterization
      of an aperiodic-modulated model.
AB  - We employ a mean-field approximation to study the Ising model with aperiodic
      modulation of its interactions in one spatial direction. Two different values for
      the exchange constant, J(A) and J(B), are present, according to the Fibonacci
      sequence. We calculate the pseudocritical temperatures for finite systems and
      extrapolate them to the thermodynamic limit. We explicitly obtain the exponents
      beta, delta, and gamma and, from the usual scaling relations for anisotropic
      models at the upper critical dimension (assumed to be 4 for the model we treat),
      we calculate alpha, nu, nu(?), eta, and eta(?). Within the framework of a
      renormalization-group approach, the Fibonacci sequence is a marginal one and we
      obtain exponents that depend on the ratio r=J(B)/J(A), as expected; however, the
      scaling relation gamma=beta(delta-1) is obeyed for all values of r we studied. We
      characterize some thermodynamic functions as log-periodic functions of their
      arguments, as expected for aperiodic-modulated models, and obtain precise values
      for the exponents from this characterization.

PMID- 22400519
TI  - Classical orbital magnetic moment in a dissipative stochastic system.
AB  - We present an analytical treatment of the dissipative-stochastic dynamics of a
      charged classical particle confined biharmonically in a plane with a uniform
      static magnetic field directed perpendicular to the plane. The stochastic
      dynamics gives a steady state in the long-time limit. We have examined the
      orbital magnetic effect of introducing a parametrized deviation (eta-1) from the
      second fluctuation-dissipation relation that connects the driving noise and the
      frictional memory kernel in the standard Langevin dynamics. The main result
      obtained here is that the moving charged particle generates a finite orbital
      magnetic moment in the steady state, and that the moment shows a crossover from
      para- to diamagnetic sign as the parameter eta is varied. It is zero for eta=1
      that makes the steady state correspond to equilibrium, as it should. The
      magnitude of the orbital magnetic moment turns out to be a nonmonotonic function
      of the applied magnetic field, tending to zero in the limit of an infinitely
      large as well as an infinitesimally small magnetic field. These results are
      discussed in the context of the classic Bohr-van Leeuwen theorem on the absence
      of classical orbital diamagnetism. Possible realization is also briefly
      discussed.

PMID- 22400520
TI  - Diffusional screening in treelike spaces: an exactly solvable diffusion-reaction
      model.
AB  - A renormalization approach is used to derive an analytic formula for the total
      current crossing the reactive surface of a Cayley tree of cylindrical tubes under
      a Helmholtz-type approximation to the full diffusion-reaction problem. We provide
      analytic conditions for the emergence of a plateau in the current-a region of
      maximum insensitivity of the current to variations in either the reaction rate
      (membrane permeability) or the diffusivity. The occurrence of such a plateau is
      associated with a partial screening regime wherein most of the active surface is
      screened to incoming diffusing particles. Large trees trade efficiency for fault
      tolerance, a valuable feature which may provide robustness to mammalian
      respiratory systems and tolerance to catalytic poisoning in chemical reactors.

PMID- 22400521
TI  - Stochastic memory: memory enhancement due to noise.
AB  - There are certain classes of resistors, capacitors, and inductors that, when
      subject to a periodic input of appropriate frequency, develop hysteresis loops in
      their characteristic response. Here we show that the hysteresis of such memory
      elements can also be induced by white noise of appropriate intensity even at very
      low frequencies of the external driving field. We illustrate this phenomenon
      using a physical model of memory resistor realized by TiO(2) thin films
      sandwiched between metallic electrodes and discuss under which conditions this
      effect can be observed experimentally. We also discuss its implications on
      existing memory systems described in the literature and the role of colored
      noise.

PMID- 22400522
TI  - Scaling of Langevin and molecular dynamics persistence times of nonhomogeneous
      fluids.
AB  - The existing solution for the Langevin equation of an anisotropic fluid allowed
      the evaluation of the position-dependent perpendicular and parallel diffusion
      coefficients, using molecular dynamics data. However, the time scale of the
      Langevin dynamics and molecular dynamics are different and an ansatz for the
      persistence probability relaxation time was needed. Here we show how the solution
      for the average persistence probability obtained from the backward Smoluchowski
      Fokker-Planck equation (SE), associated to the Langevin dynamics, scales with the
      corresponding molecular dynamics quantity. Our SE perpendicular persistence time
      is evaluated in terms of simple integrals over the equilibrium local density.
      When properly scaled by the perpendicular diffusion coefficient, it gives a good
      match with that obtained from molecular dynamics.

PMID- 22400523
TI  - Competition between quenched disorder and long-range connections: a numerical
      study of diffusion.
AB  - The problem of random walk is considered in one dimension in the simultaneous
      presence of a quenched random force field and long-range connections, the
      probability of which decays with the distance algebraically as p(l)?betal(-s).
      The dynamics are studied mainly by a numerical strong disorder renormalization
      group method. According to the results, for s>2 the long-range connections are
      irrelevant, and the mean-square displacement increases as <x(2)(t)>~(lnt)(2/psi)
      with the barrier exponent psi=1/2, which is known in one-dimensional random
      environments. For s<2, instead, the quenched disorder is found to be irrelevant,
      and the dynamical exponent is z=1 like in a homogeneous environment. At the
      critical point, s=2, the interplay between quenched disorder and long-range
      connections results in activated scaling, however, with a nontrivial barrier
      exponent psi(beta), which decays continuously with beta but is independent of the
      form of the quenched disorder. Upper and lower bounds on psi(beta) are
      established, and numerical estimates are given for various values of beta.
      Besides random walks, accurate numerical estimates of the graph dimension and the
      resistance exponent are given for various values of beta at s=2.

PMID- 22400524
TI  - Ensemble equivalence for counterion condensation on a two-dimensional charged
      disk.
AB  - We study the counterion condensation on a two-dimensional charged disk in the
      limit of infinite dilution, and compare the energy-temperature relation obtained
      from the canonical free energy and microcanonical entropy. The microcanonical
      entropy is piecewise linear in energy, and is shown to be concave for all
      energies. As a result, even though the interactions are long-ranged, the energy
      temperature relation and hence the counterion condensation transition points are
      identical in both the ensembles.

PMID- 22400525
TI  - Mean-field density functional theory of a three-phase contact line.
AB  - A three-phase contact line in a three-phase fluid system is modeled by a mean
      field density functional theory. We use a variational approach to find the Euler
      Lagrange equations. Analytic solutions are obtained in the two-phase regions at
      large distances from the contact line. We employ a triangular grid and use a
      successive overrelaxation method to find numerical solutions in the entire domain
      for the special case of equal interfacial tensions for the two-phase interfaces.
      We use the Kerins-Boiteux formula to obtain a line tension associated with the
      contact line. This line tension turns out to be negative. We associate line
      adsorption with the change of line tension as the governing potentials change.

PMID- 22400526
TI  - Phase transitions in a three-dimensional kinetic spin-1/2 Ising model with random
      field: effective-field-theory study.
AB  - The dynamical phase transitions of the kinetic Ising model in the presence of a
      random magnetic field with a bimodal probability distribution is studied by using
      effective-field theory (EFT) with correlations. We have used a Glauber-type
      stochastic dynamic to describe the time evolution of the system, where the system
      strongly depends on the H=?<H(i)(2)>(c) root mean square deviation of the
      magnetic field. The EFT dynamic equation is given for the simple cubic lattice
      (z=6), and the dynamic order parameter is calculated. The system presents
      ferromagnetic and paramagnetic states for low and high temperatures,
      respectively. Our results predict first-order transitions at low temperatures and
      large disorder strengths, which corresponds to the existence of a nonequilibrium
      tricritical point (TCP) in a phase diagram in the T-H plane. We compare the
      results with the equilibrium phase diagram, where only the first-order line is
      different. Our qualitative results are compatible with recent Monte Carlo
      simulations.

PMID- 22400527
TI  - Deterministic Josephson vortex ratchet with a load.
AB  - We investigate experimentally a deterministic underdamped Josephson vortex
      ratchet-a fluxon particle moving along a Josephson junction in an asymmetric
      periodic potential. By applying a sinusoidal driving current, one can compel the
      vortex to move in a certain direction, producing an average dc voltage across the
      junction. Being in such a rectification regime, we also load the ratchet, i.e.,
      apply an additional dc bias current I(dc) (counterforce) which tilts the
      potential so that the fluxon climbs uphill due to the ratchet effect. The value
      of the bias current at which the fluxon stops climbing up defines the strength of
      the ratchet effect and is determined experimentally. This allows us to estimate
      the loading capability of the ratchet, the output power, and the efficiency. For
      the quasistatic regime we present a simple model which delivers straightforward
      analytic expressions for the above-mentioned figures of merit.

PMID- 22400528
TI  - Linear polymers in disordered media: the shortest, the longest, and the mean self
      avoiding walk on percolation clusters.
AB  - Long linear polymers in strongly disordered media are well described by self
      avoiding walks (SAWs) on percolation clusters and a lot can be learned about the
      statistics of these polymers by studying the length distribution of SAWs on
      percolation clusters. This distribution encompasses 2 distinct averages, viz.,
      the average over the conformations of the underlying cluster and the SAW
      conformations. For the latter average, there are two basic options, one being
      static and one being kinetic. It is well known for static averaging that if the
      disorder of the underlying medium is weak, this disorder is redundant in the
      sense the renormalization group; i.e., differences to the ordered case appear
      merely in nonuniversal quantities. Using dynamical field theory, we show that the
      same holds true for kinetic averaging. Our main focus, however, lies on strong
      disorder, i.e., the medium being close to the percolation point, where disorder
      is relevant. Employing a field theory for the nonlinear random resistor network
      in conjunction with a real-world interpretation of the corresponding Feynman
      diagrams, we calculate the scaling exponents for the shortest, the longest, and
      the mean or average SAW to 2-loop order. In addition, we calculate to 2-loop
      order the entire family of multifractal exponents that governs the moments of the
      the statistical weights of the elementary constituents (bonds or sites of the
      underlying fractal cluster) contributing to the SAWs. Our RG analysis reveals
      that kinetic averaging leads to renormalizability whereas static averaging does
      not, and hence, we argue that the latter does not lead to a well-defined scaling
      limit. We discuss the possible implications of this finding for experiments and
      numerical simulations which have produced widespread results for the exponent of
      the average SAW. To corroborate our results, we also study the well-known Meir
      Harris model for SAWs on percolation clusters. We demonstrate that the Meir
      Harris model leads back up to 2-loop order to the renormalizable real-world
      formulation with kinetic averaging if the replica limit is consistently performed
      at the first possible instant in the course of the calculation.

PMID- 22400529
TI  - Analysis of wasp-waisted hysteresis loops in magnetic rocks.
AB  - The random-field Ising model of hysteresis is generalized to dilute magnets and
      is solved on a Bethe lattice. Exact expressions for the major and minor
      hysteresis loops are obtained. In the strongly dilute limit the model provides a
      simple and useful understanding of the shapes of hysteresis loops in magnetic
      rock samples.

PMID- 22400530
TI  - Parity effect and phase transitions in quantum Szilard engines.
AB  - Quantum Szilard engines with an arbitrary number of identical particles are
      studied in this paper. Analytical expressions for the total work in the low- and
      high-temperature limits are obtained. The total work depends on both the particle
      statistics, the odd-even parity, and the temperature of the system. The parity
      effect is drastic in fermion systems. An odd number of fermions perform work as
      if they were a single fermion, and an even number of fermions do not perform any
      work at all. For bosons, there exists a phase transition at a critical
      temperature under which work done by the engine is always negative. It is found
      that only above a certain temperature, bosonic quantum Szilard engine does more
      work than fermionic one. The possible experimental verification of these effects
      is discussed.

PMID- 22400531
TI  - Nonequilibrium density-matrix description of steady-state quantum transport.
AB  - With this work we investigate the stationary nonequilibrium density matrix of
      current carrying nonequilibrium steady states of in-between quantum systems that
      are connected to reservoirs. We describe the analytical procedure to obtain the
      explicit result for the reduced density matrix of quantum transport when the
      system, the connecting reservoirs, and the system-reservoir interactions are
      described by quadratic Hamiltonians. Our procedure is detailed for both
      electronic transport described by the tight-binding Hamiltonian and for phonon
      transport described by harmonic Hamiltonians. For the special case of weak system
      reservoir couplings, a more detailed description of the steady-state density
      matrix is obtained. Several paradigm transport setups for interelectrode electron
      transport and low-dimensional phonon heat flux are elucidated.

PMID- 22400532
TI  - Efficiency at maximum power output of linear irreversible Carnot-like heat
      engines.
AB  - The efficiency at maximum power output of linear irreversible Carnot-like heat
      engines is investigated based on the assumption that the rate of irreversible
      entropy production of the working substance in each "isothermal" process is a
      quadratic form of the heat exchange rate between the working substance and the
      reservoir. It is found that the maximum power output corresponds to minimizing
      the irreversible entropy production in two isothermal processes of the Carnot
      like cycle, and that the efficiency at maximum power output has the form
      eta(mP)=eta(C)/(2-gammaeta(C)), where eta(C) is the Carnot efficiency, while
      gamma depends on the heat transfer coefficients between the working substance and
      two reservoirs. The value of eta(mP) is bounded between eta(-)=eta(C)/2 and
      eta(+)=eta(C)/(2-eta(C)). These results are consistent with those obtained by
      Chen and Yan [J. Chem. Phys. 90, 3740 (1989)] based on the endoreversible
      assumption, those obtained by Esposito et al. [Phys. Rev. Lett. 105, 150603
      (2010)] based on the low-dissipation assumption, and those obtained by Schmiedl
      and Seifert [Europhys. Lett. 81, 20003 (2008)] for stochastic heat engines which
      in fact also satisfy the low-dissipation assumption. Additionally, we find that
      the endoreversible assumption happens to hold for Carnot-like heat engines
      operating at the maximum power output based on our fundamental assumption, and
      that the Carnot-like heat engines that we focused on do not strictly satisfy the
      low-dissipation assumption, which implies that the low-dissipation assumption or
      our fundamental assumption is a sufficient but non-necessary condition for the
      validity of eta(mP)=eta(C)/(2-gammaeta(C)) as well as the existence of two
      bounds, eta(-)=eta(C)/2 and eta(+)=eta(C)/(2-eta(C)).

PMID- 22400533
TI  - Connecting the microdynamics to the emergent macrovariables: self-organized
      criticality and absorbing phase transitions in the Deterministic Lattice Gas.
AB  - We reinvestigate the Deterministic Lattice Gas introduced as a paradigmatic model
      of the 1/f spectra [Phys. Rev. Lett. 64, 3103 (1990)] arising according to the
      self-organized criticality scenario. We demonstrate that the density fluctuations
      exhibit an unexpected dependence on systems size and relate the finding to
      effective Langevin equations. The low-density behavior is controlled by the
      critical properties of the gas at the absorbing state phase transition. We also
      show that the deterministic lattice gas is in the Manna universality class of
      absorbing state phase transitions. This is in contrast to expectations in the
      literature that suggested that the entirely deterministic nature of the dynamics
      would put the model in a different universality class. To our knowledge this is
      the first fully deterministic member of the Manna universality class.

PMID- 22400534
TI  - Quantized breather excitations of Fermi-Pasta-Ulam lattices.
AB  - We have calculated the lowest energy quantized breather excitations of both the
      beta and the alpha Fermi-Pasta-Ulam monoatomic lattices and the diatomic beta
      lattice within the ladder approximation. While the classical breather excitations
      form continua, the quantized breather excitations form a discrete hierarchy
      labeled by a quantum number n. Although the number of phonons is not conserved,
      the breather excitations correspond to multiple bound states of phonons. The n=2
      breather spectra are composed of resonances in the two-phonon continuum and of
      discrete branches of infinitely long-lived excitations. The nonlinear attributes
      of these excitations become more pronounced at elevated temperatures. The
      calculated n=2 breather and the resonance of the monoatomic beta lattice
      hybridize and exchange identity at the zone boundary and are in reasonable
      agreement with the results of previous calculations using the number-conserving
      approximation. However, by contrast, the breather spectrum of the alpha
      monoatomic lattice couples resonantly with the single-phonon spectrum and cannot
      be calculated within a number-conserving approximation. Furthermore, we show that
      for sufficiently strong nonlinearity, the alpha lattice breathers can be observed
      directly through the single-phonon inelastic neutron-scattering spectrum. As the
      temperature is increased, the single-phonon dispersion relation for the alpha
      lattice becomes progressively softer as the lattice instability is approached.
      For the diatomic beta lattice, it is found that there are three distinct branches
      of n=2 breather dispersion relations, which are associated with three distinct
      two-phonon continua. The two-phonon excitations form three distinct continua: One
      continuum corresponds to the motion of two independent acoustic phonons, another
      to the motion of two independent optic phonons, and the last continuum is formed
      by propagation of two phonons that are one of each character. Each breather
      dispersion relation is split off the top from of its associated continuum and
      remains within the forbidden gaps between the continua. The energy splittings
      from the top of the continua rapidly increase, and the dispersions rapidly
      decrease with the decreasing energy widths of the associated continua. This
      finding is in agreement with recent observations of sharp branches of nonlinear
      vibrational modes in NaI through inelastic neutron-scattering measurements.
      Furthermore, since the band widths of the various continua successively narrow as
      the magnitude of their characteristic excitation energies increase, the finding
      is also in agreement the theoretical prediction that breather excitations in
      discrete lattices should be localized in the classical limit.

PMID- 22400535
TI  - Time needed to board an airplane: a power law and the structure behind it.
AB  - A simple model for the boarding of an airplane is studied. Passengers have
      reserved seats but enter the airplane in arbitrary order. Queues are formed along
      the aisle, as some passengers have to wait to reach the seats for which they have
      reservation. We label a passenger by the number of his or her reserved seat. In
      most cases the boarding process is much slower than for the optimal situation,
      where passenger and seat orders are identical. We study this dynamical system by
      calculating the average boarding time when all permutations of N passengers are
      given equal weight. To first order, the boarding time for a given permutation
      (ordering) of the passengers is given by the number s of sequences of
      monotonically increasing values in the permutation. We show that the distribution
      of s is symmetric on [1,N], which leads to an average boarding time (N+1)/2. We
      have found an exact expression for s and have shown that the full distribution of
      s approaches a normal distribution as N increases. However, there are significant
      corrections to the first-order results, due to certain correlations between
      passenger ordering and the substrate (seat ordering). This occurs for some cases
      in which the sequence of the seats is partially mirrored in the passenger
      ordering. These cases with correlations have a boarding time that is lower than
      predicted by the first-order results. The large number of cases with reduced
      boarding times have been classified. We also give some indicative results on the
      geometry of the correlations, with sorting into geometry groups. With increasing
      N, both the number of correlation types and the number of cases belonging to each
      type increase rapidly. Using enumeration we find that as a result of these
      correlations the average boarding time behaves like N(alpha), with alpha?0.69, as
      compared with alpha=1.0 for the first-order approximation.

PMID- 22400536
TI  - Diffusion-mediated geminate reactions under excluded volume interactions.
AB  - In this paper, influence of crowding by inert particles on the geminate reaction
      kinetics is theoretically investigated. Time evolution equations for the survival
      probability of a geminate pair are derived from the master equation taking into
      account the correlation among all diffusing particles, and the results are
      compared with those obtained by Monte Carlo simulations. In general, excluded
      volume interactions by the inert particles slow down the diffusive motion of
      reactants. However, when the initial concentration of the inert particles is
      uniform and high, we show that additional influence of interference between
      reaction and correlated diffusion accelerates the transient decay of the survival
      probability in the diffusion-controlled limit. We also study the escape
      probability for a nonuniform initial distribution of the inert particles by
      taking the continuous limit in space. We show that reaction yield is increased
      when the reaction proceeds in the presence of a positive density gradient of the
      inert particles which inhibits the escape of reactants. The effect can be
      interpreted as a cage effect.

PMID- 22400537
TI  - Counting statistics: a Feynman-Kac perspective.
AB  - By building upon a Feynman-Kac formalism, we assess the distribution of the
      number of collisions in a given region for a broad class of discrete-time random
      walks in absorbing and nonabsorbing media. We derive the evolution equation for
      the generating function of the number of collisions, and we complete our analysis
      by examining the moments of the distribution and their relation to the walker
      equilibrium density. Some significant applications are discussed in detail: in
      particular, we revisit the gambler's ruin problem and generalize to random walks
      with absorption the arcsine law for the number of collisions on the half-line.

PMID- 22400538
TI  - Thermalization and quantum correlations in exactly solvable models.
AB  - The generalized Gibbs ensemble introduced for describing few-body correlations in
      exactly solvable systems following a quantum quench is related to the nonergodic
      way in which operators sample, in the limit of infinite time after the quench,
      the quantum correlations present in the initial state. The nonergodicity of the
      correlations is thus shown analyticallyto imply the equivalence with the
      generalized Gibbs ensemble for quantum Ising and XX spin chains as well as for
      the Luttinger model the thermodynamic limit, and for a broad class of initial
      states and correlation functions of both local and nonlocal operators.

PMID- 22400539
TI  - Dynamics of competitive learning: the role of updates and memory.
AB  - We examine the effects of memory and different updating paradigms in a game
      theoretic model of competitive learning, where agents are influenced in their
      choice of strategy by both the choices made by, and the consequent success rates
      of, their immediate neighbors. We apply parallel and sequential updates in all
      possible combinations to the two competing rules and find, typically, that the
      phase diagram of the model consists of a disordered phase separating two ordered
      phases at coexistence. A major result is that the corresponding critical
      exponents belong to the generalized universality class of the voter model. When
      the two strategies are distinct but not too different, we find the expected
      linear-response behavior as a function of their difference. Finally, we look at
      the extreme situation when a superior strategy, accompanied by a short memory of
      earlier outcomes, is pitted against its inverse; interestingly, we find that a
      long memory of earlier outcomes can occasionally compensate for the choice of a
      globally inferior strategy.

PMID- 22400540
TI  - Conditions for the validity of the quantum Langevin equation.
AB  - From microscopic models, a Langevin equation can, in general, be derived only as
      an approximation. Two possible conditions to validate this approximation are
      studied. One is, for a linear Langevin equation, that the frequency of the
      Fourier transform should be close to the natural frequency of the system. The
      other is by the assumption of "slow" variables. We test this method by comparison
      with an exactly soluble model and point out its limitations. We base our
      discussion on two approaches. The first is a direct, elementary treatment of
      Senitzky. The second is via a generalized Langevin equation as an intermediate
      step.

PMID- 22400541
TI  - Isotropic-nematic phase diagram for interacting rigid rods on two-dimensional
      lattices.
AB  - The phase behavior of interacting rigid rods of length k (k-mers) on two
      dimensional square and triangular lattices has been studied by theoretical
      calculations in the framework of the lattice-gas model. The process was analyzed
      by comparing the dependence on coverage of the free energy per site of an
      isotropic submonolayer of interacting k-mers f(iso)(theta) with that
      corresponding to a fully aligned (nematic) system f(nem)(theta). The existence of
      an intersection point between the curves f(iso)(theta) and f(nem)(theta), which
      is indicative of the occurrence of an isotropic-nematic phase transition in the
      adlayer, allowed us to obtain the complete (temperature, coverage, k-mer size)
      phase diagram of the system.

PMID- 22400542
TI  - Tunneling and percolation transport regimes in segregated composites.
AB  - We consider the problem of electron transport in segregated conductor-insulator
      composites in which the conducting particles are connected to all others via
      tunneling conductances, thus forming a global tunneling-connected resistor
      network. Segregation is induced by the presence of large insulating particles,
      which forbid the much smaller conducting fillers from occupying uniformly the
      three-dimensional volume of the composite. By considering both colloidal-like and
      granular-like dispersions of the conducting phase, modeled respectively by
      dispersions in the continuum and in the lattice, we evaluate by Monte Carlo
      simulations the effect of segregation on the composite conductivity sigma, and
      show that an effective-medium theory applied to the tunneling network reproduces
      accurately the Monte Carlo results. The theory clarifies that the main effect of
      segregation in the continuum is that of reducing the mean interparticle
      distances, leading to a strong enhancement of the conductivity. In the lattice
      segregation case the conductivity enhancement is instead given by the lowering of
      the percolation thresholds for first and beyond-first nearest neighbors. Our
      results generalize to segregated composites the tunneling-based description of
      both the percolation and hopping regimes introduced previously for homogeneous
      disordered systems.

PMID- 22400543
TI  - Impact of boundaries on fully connected random geometric networks.
AB  - Many complex networks exhibit a percolation transition involving a macroscopic
      connected component, with universal features largely independent of the
      microscopic model and the macroscopic domain geometry. In contrast, we show that
      the transition to full connectivity is strongly influenced by details of the
      boundary, but observe an alternative form of universality. Our approach correctly
      distinguishes connectivity properties of networks in domains with equal bulk
      contributions. It also facilitates system design to promote or avoid full
      connectivity for diverse geometries in arbitrary dimension.

PMID- 22400544
TI  - Phase transitions in the first-passage time of scale-invariant correlated
      processes.
AB  - A key quantity describing the dynamics of complex systems is the first-passage
      time (FPT). The statistical properties of FPT depend on the specifics of the
      underlying system dynamics. We present a unified approach to account for the
      diversity of statistical behaviors of FPT observed in real-world systems. We find
      three distinct regimes, separated by two transition points, with fundamentally
      different behavior for FPT as a function of increasing strength of the
      correlations in the system dynamics: stretched exponential, power-law, and
      saturation regimes. In the saturation regime, the average length of FPT diverges
      proportionally to the system size, with important implications for understanding
      electronic delocalization in one-dimensional correlated-disordered systems.

PMID- 22400545
TI  - Effective field theory approach to fluctuation-induced forces between colloids at
      an interface.
AB  - We discuss an effective field theory (EFT) approach to the computation of
      fluctuation-induced interactions between particles bound to a thermally
      fluctuating fluid surface controlled by surface tension. By describing particles
      as points, EFT avoids computing functional integrals subject to difficult
      constraints. Still, all information pertaining to particle size and shape is
      systematically restored by amending the surface Hamiltonian with a derivative
      expansion. The free energy is obtained as a cumulant expansion, for which
      straightforward techniques exist. We derive a completedescription for rigid
      axisymmetric objects, which allows us to develop a full asymptotic expansion-in
      powers of the inverse distance-for the pair interaction. We also demonstrate by a
      few examples the efficiency with which multibody interactions can be computed.
      Moreover, although the main advantage of the EFT approach lies in explicit
      computation, we discuss how one can infer certain features of cases involving
      flexible or anisotropic objects. The EFT description also permits a systematic
      computation of ground-state surface-mediated interactions, which we illustrate
      with a few examples.

PMID- 22400546
TI  - Approach to typicality in many-body quantum systems.
AB  - The recent discovery that for large Hilbert spaces, almost all (that is, typical)
      Hamiltonians have eigenstates that place small subsystems in thermal equilibrium,
      has shed much light on the origins of irreversibility and thermalization. Here we
      give numerical evidence that many-body lattice systems generically approach
      typicality as the number of subsystems is increased, and thus provide further
      support for the eigenstate thermalization hypothesis. Our results indicate that
      the deviation of many-body systems from typicality decreases exponentially with
      the number of systems. Further, by averaging over a number of randomly selected
      nearest-neighbor interactions, we obtain a powerlaw for the atypicality as a
      function of the Hilbert space dimension, distinct from the power law possessed by
      random Hamiltonians.

PMID- 22400547
TI  - Mixed population of competing totally asymmetric simple exclusion processes with
      a shared reservoir of particles.
AB  - We introduce a mean-field theoretical framework to describe multiple totally
      asymmetric simple exclusion processes (TASEPs) with different lattice lengths and
      entry and exit rates, competing for a finite reservoir of particles. We present
      relations for the partitioning of particles between the reservoir and the
      lattices: These relations allow us to show that competition for particles can
      have nontrivial effects on the phase behavior of individual lattices. For a
      system with nonidentical lattices, we find that when a subset of lattices
      undergoes a phase transition from low to high density, the entire set of lattice
      currents becomes independent of total particle number. We generalize our approach
      to systems with a continuous distribution of lattice parameters, for which we
      demonstrate that measurements of the current carried by a single lattice type can
      be used to extract the entire distribution of lattice parameters. Our approach
      applies to populations of TASEPs with any distribution of lattice parameters and
      could easily be extended beyond the mean-field case.

PMID- 22400548
TI  - Electrical percolation networks of carbon nanotubes in a shear flow.
AB  - The effect of shear on the electrical percolation network of carbon nanotube
      (CNT)-polymer composites is investigated using computer simulations.
      Configurations of CNTs in a simple shear, obtained by using Monte Carlo
      simulations, are used to locate the electrical percolation network of CNTs and
      calculate the electric conductivity. When exposed to the shear, CNTs align
      parallel to the shear direction and the electrical percolation threshold CNT
      concentration decreases. Meanwhile, after a certain period of the shear
      imposition above a critical shear rate, CNTs begin to form an aggregate and the
      percolating network of CNTs is broken, thus decreasing the electric conductivity
      significantly. We also construct quasiphase diagrams for the aggregate formation
      and the electrical percolation network formation to investigate the effect of the
      shear rate and CNT concentration.

PMID- 22400549
TI  - Generalized Pauli principle for particles with distinguishable traits.
AB  - The s=3/2 Ising spin chain with uniform nearest-neighbor coupling, quadratic
      single-site potential, and magnetic field is shown to be equivalent to a system
      of 17 species of particles with internal structure. The same set of particles
      (with different energies) is shown to generate the spectrum of the s=1/2 Ising
      chain with dimerized nearest-neighbor coupling. The particles are free of
      interaction energies even at high densities. The mutual exclusion statistics of
      particles from all species is determined by their internal structure and encoded
      in a generalized Pauli principle. The exact statistical mechanical analysis can
      be performed for thermodynamically open or closed systems and with arbitrary
      energies assigned to all particle species. Special circumstances make it possible
      to merge two or more species into a single species. All traits that distinguish
      the original species become ignorable. The particles from the merged species are
      effectively indistinguishable and obey modified exclusion statistics. Different
      mergers may yield the same end product, implying that the inverse process
      (splitting any species into subspecies) is not unique. In a macroscopic system of
      two merged species at thermal equilibrium, the concentrations of the original
      species satisfy a functional relation governed by their mutual statistical
      interaction. That relation is derivable from an extremum principle. In the Ising
      context the system is open and the particle energies depend on the Hamiltonian
      parameters. Simple models of polymerization and solitonic paramagnetism each
      represent a closed system of two species that can transform into each other. Here
      they represent distinguishable traits with different energies of the same
      physical particle.

PMID- 22400550
TI  - Power-law behavior in a cascade process with stopping events: a solvable model.
AB  - The present paper proposes a stochastic model to be solved analytically, and a
      power-law-like distribution is derived. This model is formulated based on a
      cascade fracture with the additional effect that each fragment at each stage of a
      cascade ceases fracture with a certain probability. When the probability is
      constant, the exponent of the power-law cumulative distribution lies between -1
      and 0, depending not only on the probability but the distribution of fracture
      points. Whereas, when the probability depends on the size of a fragment, the
      exponent is less than -1, irrespective of the distribution of fracture points.
      The applicability of our model is also discussed.

PMID- 22400551
TI  - Efficiency and its bounds for thermal engines at maximum power using Newton's law
      of cooling.
AB  - We study a thermal engine model for which Newton's cooling law is obeyed during
      heat transfer processes. The thermal efficiency and its bounds at maximum output
      power are derived and discussed. This model, though quite simple, can be applied
      not only to Carnot engines but also to four other types of engines. For the long
      thermal contact time limit, new bounds, tighter than what were known before, are
      obtained. In this case, this model can simulate Otto, Joule-Brayton, Diesel, and
      Atkinson engines. While in the short contact time limit, which corresponds to the
      Carnot cycle, the same efficiency bounds as that from Esposito et al. [Phys. Rev.
      Lett. 105, 150603 (2010)] are derived. In both cases, the thermal efficiency
      decreases as the ratio between the heat capacities of the working medium during
      heating and cooling stages increases. This might provide instructions for
      designing real engines.

PMID- 22400552
TI  - Different diffusive regimes, generalized Langevin and diffusion equations.
AB  - We investigate a generalized Langevin equation (GLE) in the presence of an
      additive noise characterized by the mixture of the usual white noise and an
      arbitrary one. This scenario lead us to a wide class of diffusive processes, in
      particular the ones whose noise correlation functions are governed by power laws,
      exponentials, and Mittag-Leffler functions. The results show the presence of
      different diffusive regimes related to the spreading of the system. In addition,
      we obtain a fractional diffusionlike equation from the GLE, confirming the
      results for long time.

PMID- 22400553
TI  - Absolute negative mobility in a vibrational motor.
AB  - An anomalous transport phenomenon termed absolute negative mobility (ANM) was
      observed in a vibrational motor, where an additional time-periodic signal filled
      the role usually played by noise in a Brownian motor. Within a tailored parameter
      regime, the ANM behavior is maximized at two regimes upon variation of the bias.
      The observed ANM still survives at a wide range of the driving strength and
      angular frequency of the additional signal.

PMID- 22400554
TI  - Cooperation and age structure in spatial games.
AB  - We study the evolution of cooperation in evolutionary spatial games when the
      payoff correlates with the increasing age of players (the level of correlation is
      set through a single parameter, alpha). The demographic heterogeneous age
      distribution, directly affecting the outcome of the game, is thus shown to be
      responsible for enhancing the cooperative behavior in the population. In
      particular, moderate values of alpha allow cooperators not only to survive but to
      outcompete defectors, even when the temptation to defect is large and the
      ageless, standard alpha=0 model does not sustain cooperation. The interplay
      between age structure and noise is also considered, and we obtain the conditions
      for optimal levels of cooperation.

PMID- 22400555
TI  - Noise-induced volatility of collective dynamics.
AB  - Noise-induced volatility refers to a phenomenon of increased level of
      fluctuations in the collective dynamics of bistable units in the presence of a
      rapidly varying external signal, and intermediate noise levels. The archetypical
      signature of this phenomenon is that-beyond the increase in the level of
      fluctuations-the response of the system becomes uncorrelated with the external
      driving force, making it different from stochastic resonance. Numerical
      simulations and an analytical theory of a stochastic dynamical version of the
      Ising model on regular and random networks demonstrate the ubiquity and
      robustness of this phenomenon, which is argued to be a possible cause of excess
      volatility in financial markets, of enhanced effective temperatures in a variety
      of out-of-equilibrium systems, and of strong selective responses of immune
      systems of complex biological organisms. Extensive numerical simulations are
      compared with a mean-field theory for different network topologies.

PMID- 22400556
TI  - Mean-field approximation for spacing distribution functions in classical systems.
AB  - We propose a mean-field method to calculate approximately the spacing
      distribution functions p((n))(s) in one-dimensional classical many-particle
      systems. We compare our method with two other commonly used methods, the
      independent interval approximation and the extended Wigner surmise. In our mean
      field approach, p((n))(s) is calculated from a set of Langevin equations, which
      are decoupled by using a mean-field approximation. We find that in spite of its
      simplicity, the mean-field approximation provides good results in several
      systems. We offer many examples illustrating that the three previously mentioned
      methods give a reasonable description of the statistical behavior of the system.
      The physical interpretation of each method is also discussed.

PMID- 22400557
TI  - Limiting shapes of Ising droplets, Ising fingers, and Ising solitons.
AB  - We examine the evolution of an Ising ferromagnet endowed with zero-temperature
      single spin-flip dynamics. A large droplet of one phase in the sea of the
      opposite phase eventually disappears. An interesting behavior occurs in the
      intermediate regime when the droplet is still very large compared to the lattice
      spacing, but already very small compared to the initial size. In this regime the
      shape of the droplet is essentially deterministic (fluctuations are negligible in
      comparison with characteristic size). In two dimensions the shape is also
      universal, that is, independent of the initial shape. We analytically determine
      the limiting shape of the Ising droplet on the square lattice. When the initial
      state is a semi-infinite stripe of one phase in the sea of the opposite phase, it
      evolves into a finger which translates along its axis. We determine the limiting
      shape and the velocity of the Ising finger on the square lattice. An analog of
      the Ising finger on the cubic lattice is the translating Ising soliton. We show
      that far away from the tip, the cross-section of the Ising soliton coincides with
      the limiting shape of the two-dimensional Ising droplet and we determine a
      relation between the cross-section area, the distance from the tip, and the
      velocity of the soliton.

PMID- 22400558
TI  - Anisotropic velocity statistics of topological defects under shear flow.
AB  - We report numerical results on the velocity statistics of topological defects
      during the dynamics of phase ordering and nonrelaxational evolution assisted by
      an external shear flow. We propose a numerically efficient tracking method for
      finding the position and velocity of defects and apply it to vortices in a
      uniform field and dislocations in anisotropic stripe patterns. During
      relaxational dynamics, the distribution function of the velocity fluctuations is
      characterized by a dynamical scaling with a scaling function that has a robust
      algebraic tail with an inverse cube power law. This is characteristic of defects
      of codimension 2, e.g., point defects in two dimensions and filaments in three
      dimensions, regardless of whether the motion is isotropic (as for vortices) or
      highly anisotropic (as for dislocations). However, the anisotropic dislocation
      motion leads to anisotropic statistical properties when the interaction between
      defects and their motion is influenced by the presence of an external shear flow
      transverse to the stripe orientation.

PMID- 22400559
TI  - Influence of polydispersity on micromechanics of granular materials.
AB  - We study the effect of polydispersity on the macroscopic physical properties of
      granular packings in two and three dimensions. A mean-field approach is developed
      to approximate the macroscale quantities as functions of the microscopic ones. We
      show that the trace of the fabric and stress tensors are proportional to the mean
      packing properties (e.g., packing fraction, average coordination number, and
      average normal force) and dimensionless correction factors, which depend only on
      the moments of the particle-size distribution. Similar results are obtained for
      the elements of the stiffness tensor of isotropic packings in the linear affine
      response regime. Our theoretical predictions are in good agreement with the
      simulation results.

PMID- 22400560
TI  - Impurity in a sheared inelastic Maxwell gas.
AB  - The Boltzmann equation for inelastic Maxwell models is considered in order to
      investigate the dynamics of an impurity (or intruder) immersed in a granular gas
      driven by a uniform shear flow. The analysis is based on an exact solution of the
      Boltzmann equation for a granular binary mixture. It applies for conditions
      arbitrarily far from equilibrium (arbitrary values of the shear rate a) and for
      arbitrary values of the parameters of the mixture (particle masses m(i), mole
      fractions x(i), and coefficients of restitution alpha(ij)). In the tracer limit
      where the mole fraction of the intruder species vanishes, a nonequilibrium phase
      transition takes place. We thereby identify ordered phases where the intruder
      bears a finite contribution to the properties of the mixture, in a region of
      parameter space that is worked out in detail. These findings extend previous
      results obtained for ordinary Maxwell gases, and further show that dissipation
      leads to new ordered phases.

PMID- 22400561
TI  - Computational topology for configuration spaces of hard disks.
AB  - We explore the topology of configuration spaces of hard disks experimentally and
      show that several changes in the topology can already be observed with a small
      number of particles. The results illustrate a theorem of Baryshnikov, Bubenik,
      and Kahle  that critical points correspond to configurations of disks with
      balanced mechanical stresses and suggest conjectures about the asymptotic
      topology as the number of disks tends to infinity.

PMID- 22400562
TI  - Taxonomy of granular rheology from grain property networks.
AB  - We construct complex networks from symbolic time series of particle properties
      within a dense quasistatically deforming granular assembly subjected to biaxial
      compression. The structure of the resulting networks embodies the evolving
      structural rearrangements in the granular material, in both contact forces and
      contact topologies. These rearrangements are usefully summarized through standard
      network statistics as well as building block motifs and community structures.
      Dense granular media respond to applied compression and shear by a process of
      self-organization to form two cooperatively evolving structures comprising the
      major load-bearing columnlike force chains, and the lateral trusslike three-cycle
      triangle topologies. We construct networks summarizing their individual evolution
      based on relationships between symbolic time series indicating a particle's
      chronological force chain and three-cycle membership histories. We test which
      particle membership histories are similar with respect to each other through the
      information theory-based measure of Hamming distance. The complex networks
      summarize the essential structural rearrangements, while the community structures
      within the networks partition the material into distinct zones of deformation,
      including interlacing subregions of failure inside the shear band. The taxonomy
      of granular rheology at the mesoscopic scale distills the inelastic structural
      rearrangements throughout loading history down to its core elements, and should
      lay bare an objective and physics-based formalism for thermodynamic internal
      variables and associated evolution laws.

PMID- 22400563
TI  - Microstructure evolution during impact on granular matter.
AB  - We study the impact of an intruder on a dense granular material. The process of
      impact and interaction between the intruder and the granular particles is modeled
      using discrete element simulations in two spatial dimensions. In the first part
      of the paper we discuss how the intruder's dynamics depends on (1) the intruder's
      properties, including its size, shape and composition, (2) the properties of the
      grains, including friction, polydispersity, structural order, and elasticity, and
      (3) the properties of the system, including its size and gravitational field. It
      is found that polydispersity and related structural order, and frictional
      properties of the granular particles, play a crucial role in determining impact
      dynamics. In the second part of the paper we consider the response of the
      granular system itself. We discuss the force networks that develop, including
      their topological evolution. The influence of friction and structural order on
      force propagation, including the transition from hyperbolic-like to elastic-like
      behavior is discussed, as well as the affine and nonaffine components of the
      grain dynamics. Several broad observations include the following: tangential
      forces between granular particles are found to play a crucial role in determining
      impact dynamics; both force networks and particle dynamics are correlated with
      the dynamics of the intruder itself.

PMID- 22400564
TI  - Analytical model for tracer dispersion in porous media.
AB  - In this work, we present a novel analytical model for tracer dispersion in
      laminar flow through porous media. Based on a straightforward physical argument,
      it describes the generic behavior of dispersion over a wide range of Peclet
      numbers (exceeding eight orders of magnitude). In particular, the model
      accurately captures the intermediate scaling behavior of longitudinal dispersion,
      obviating the need to subdivide the dispersional behavior into a number of
      disjunct regimes or using empirical power-law expressions. The analysis also
      suggests the possible existence of a new material property, the critical Peclet
      number, reflecting the mesoscale geometric properties of the microscopic pore
      structure.

PMID- 22400565
TI  - Angular particle sliding down a transversally vibrated smooth plane.
AB  - We present a theoretical, numerical, and experimental study about the sliding
      motion of an angular particle down a vibrated smooth plane. The model is based on
      a Coulomb's friction law with a unique friction coefficient. The model is solved
      numerically and is tested with controlled experiments. Different motion regimes
      are identified and the particle behavior is governed by two dimensionless
      parameters. The comparison between experimental and numerical results gives an
      indirect access to the dynamic friction coefficient.

PMID- 22400566
TI  - Contact percolation transition in athermal particulate systems.
AB  - Typical quasistatic compression algorithms for generating jammed packings of
      purely repulsive, frictionless particles begin with dilute configurations and
      then apply successive compressions with the relaxation of the elastic energy
      allowed between each compression step. It is well known that during isotropic
      compression these systems undergo a first-order-like jamming transition at
      packing fraction phi(J) from an unjammed state with zero pressure and no force
      bearing contacts to a jammed, rigid state with nonzero pressure, a percolating
      network of force-bearing contacts, and contact number z=2d, where d is the
      spatial dimension. Using computer simulations of two-dimensional systems with
      monodisperse and bidisperse particle size distributions, we investigate the
      second-order-like contact percolation transition, which precedes the jamming
      transition with phi(P)<phi(J) and signals the formation of a system-spanning
      cluster of non-force-bearing contacts between particles. By measuring the number
      of nonfloppy modes of the dynamical matrix, the displacement field between
      successive compression steps, and the overlap between the adjacency matrix, which
      represents the network of contacting grains, at phi and phi(J), we find that the
      contact percolation transition also signals the onset of a nontrivial mechanical
      response to applied stress. Our results show that cooperative particle motion
      occurs in unjammed systems significantly below the jamming transition for
      phi(P)<phi<phi(J), not only for jammed systems with phi>phi(J).

PMID- 22400567
TI  - Fluid dynamics of dilatant fluids.
AB  - A dense mixture of granules and liquid often shows a severe shear thickening and
      is called a dilatant fluid. We construct a fluid dynamics model for the dilatant
      fluid by introducing a phenomenological state variable for a local state of
      dispersed particles. With simple assumptions for an equation of the state
      variable, we demonstrate that the model can describe basic features of the
      dilatant fluid such as the stress-shear rate curve that represents discontinuous
      severe shear thickening, hysteresis upon changing shear rate, and instantaneous
      hardening upon external impact. An analysis of the model reveals that the shear
      thickening fluid shows an instability in a shear flow for some regime and
      exhibits the shear thickening oscillation (i.e., the oscillatory shear flow
      alternating between the thickened and the relaxed states). The results of
      numerical simulations are presented for one- and two-dimensional systems.

PMID- 22400568
TI  - Dynamics in dense hard-sphere colloidal suspensions.
AB  - The dynamic behavior of a hard-sphere colloidal suspension was studied by x-ray
      photon correlation spectroscopy and small-angle x-ray scattering over a wide
      range of particle volume fractions. The short-time mobility of the particles was
      found to be smaller than that of free particles even at relatively low
      concentrations, showing the importance of indirect hydrodynamic interactions.
      Hydrodynamic functions were derived from the data, and for moderate particle
      volume fractions (Phi<= 0.40) there is good agreement with earlier many-body
      theory calculations by Beenakker and Mazur [Physica A 120, 349 (1984)]. Important
      discrepancies appear at higher concentrations, above Phi~ 0.40, where the
      hydrodynamic effects are overestimated by the Beenakker-Mazur theory, but
      predicted accurately by an accelerated Stokesian dynamics algorithm developed by
      Banchio and Brady [J. Chem. Phys. 118, 10323 (2003)]. For the relaxation rates,
      good agreement was also found between the experimental data and a scaling form
      predicted by the mode coupling theory. In the high concentration range, with the
      fluid suspensions approaching the glass transition, the long-time diffusion
      coefficient was compared with the short-time collective diffusion coefficient to
      verify a scaling relation previously proposed by Segre and Pusey [Phys. Rev.
      Lett. 77, 771 (1996)]. We discuss our results in view of previous experimental
      attempts to validate this scaling law [L. Lurio et al., Phys. Rev. Lett. 84, 785
      (2000)].

PMID- 22400569
TI  - Aspect-ratio-dependent phase transitions and concentration fluctuations in
      aqueous colloidal dispersions of charged platelike particles.
AB  - Phase transitions of aqueous colloidal dispersions of charged platelike particles
      of niobate nanosheets were investigated as a function of the aspect ratio
      (r(asp)) and particle volume concentration (phi(p)) by means of small-angle
      neutron scattering and small-angle x-ray scattering. The results elucidated the
      following three pieces of evidence: (1) the macroscopic phase separation of the
      dispersions into an isotropic phase and a liquid crystalline (LC) phase under the
      conditions of (a) varying r(asp) (1.3*10(-4) <= r(asp) <= 2.5*10(-3)) at a
      constant phi(p) = 0.01 and (b) varying phi(p) (0.01 <= phi(p) <= 0.025) at a
      constant r(asp) = 2.5*10(-3), a mechanism of which is proposed in the text, where
      r(asp) = d/ L, with d and L being thickness and the average lateral size of the
      plates, respectively; (2) the r(asp)-induced phase transition of the LC phase
      from a nematic phase to a highly periodic layered phase, the line shapes of the
      scattering peaks of which were examined by Caille's analysis, upon increasing
      r(asp) under the condition (a); (3) the LC phase having remarkable concentration
      fluctuations of the particles which are totally unexpected for the conventional
      lyotropic molecular LC but which are anticipated to be general for the platelike
      colloidal particles.

PMID- 22400570
TI  - Dynamics of localized particles from density functional theory.
AB  - A fundamental assumption of the dynamical density functional theory (DDFT) of
      colloidal systems is that a grand-canonical free-energy functional may be
      employed to generate the thermodynamic driving forces. Using one-dimensional hard
      rods as a model system, we analyze the validity of this key assumption and show
      that unphysical self-interactions of the tagged particle density fields, arising
      from coupling to a particle reservoir, are responsible for the excessively fast
      relaxation predicted by the theory. Moreover, our findings suggest that even
      employing a canonical functional would not lead to an improvement for many
      particle systems, if only the total density is considered. We present several
      possible schemes to suppress these effects by incorporating tagged densities.
      When applied to confined systems, we demonstrate, using a simple example, that
      DDFT necessarily leads to delocalized tagged particle density distributions,
      which do not respect the fundamental geometrical constraints apparent in Brownian
      dynamics simulation data. The implication of these results for possible
      applications of DDFT to treat the glass transition are discussed.

PMID- 22400571
TI  - Survey of morphologies formed in the wake of an enslaved phase-separation front
      in two dimensions.
AB  - A phase-separation front will leave in its wake a phase-separated morphology that
      differs markedly from homogeneous phase-separation morphologies. For a purely
      diffusive system such a front, moving with constant velocity, will generate very
      regular, nonequilibrium structures. We present here a numerical study of these
      fronts using a lattice Boltzmann method. In two dimensions these structures are
      regular stripes or droplet arrays. In general the kind and orientation of the
      selected morphology and the size of the domains depends on the speed of the front
      as well as the composition of the material overtaken by the phase-separation
      front. We present a survey of morphologies as a function of these two parameters.
      We show that the resulting morphologies are initial condition dependent. We then
      examine which of the potential morphologies is the most stable. An analytical
      analysis for symmetrical compositions predicts the transition point from
      orthogonal to parallel stripes.

PMID- 22400572
TI  - Jamming, relaxation, and crystallization of a supercooled fluid in a three
      dimensional lattice.
AB  - Off-equilibrium dynamics of a three-dimensional lattice model with nearest- and
      next-nearest-neighbors exclusions is studied. At equilibrium, the model undergoes
      a first-order fluid-solid transition. Nonequilibrium filling, through random
      sequential adsorption with diffusion, creates amorphous structures and terminates
      at a disordered state with random closest packing density that lies in the
      equilibrium solid regime. The approach toward random closest packing is
      characterized by two distinct power-law regimes, reflecting the formation of
      small densely packed grains in the long-time regime of the filling process. We
      then study the fixed-density relaxation of these amorphous structures toward the
      solid phase. The route to crystallization for the high-density, deeply
      supercooled regime is shown to deviate from the simple grain growth proposed by
      classical nucleation theory. Our measurements suggest that relaxation in this
      regime is driven mainly by coalescence of neighboring crystallized grains which
      exist in the initial amorphous state.

PMID- 22400573
TI  - Ratio of effective temperature to pressure controls the mobility of sheared hard
      spheres.
AB  - Using molecular dynamics simulations, we calculate fluctuations and responses for
      steadily sheared hard spheres over a wide range of packing fractions phi and
      shear strain rates gamma[over ], using two different methods to dissipate energy.
      To a good approximation, shear stress and density fluctuations are related to
      their associated response functions by a single effective temperature T(eff) that
      is equal to or larger than the kinetic temperature T(kin). We find a crossover in
      the relationship between the relaxation time tau and the the nondimensionalized
      effective temperature T(eff)/psigma(3), where p is the pressure and sigma is the
      sphere diameter. In the solid response regime, the behavior at a fixed packing
      fraction satisfies tau gamma?exp(-cpsigma(3)/T(eff)), where c depends weakly on
      phi, suggesting that the average local yield strain is controlled by the
      effective temperature in a way that is consistent with shear transformation zone
      theory. In the fluid response regime, the relaxation time depends on
      T(eff)/psigma(3) as it depends on T(kin)/psigma(3) in equilibrium. This regime
      includes both near-equilibrium conditions where T(eff)?T(kin) and far-from
      equilibrium conditions where T(eff)?T(kin). We discuss the implications of our
      results for systems with soft repulsive interactions.

PMID- 22400574
TI  - Solubility and transport of cationic and anionic patterned nanoparticles.
AB  - We analyze bulk diffusion and transport through hydrophobic nanochannels of
      nanoparticles (NPs) with different hydrophobic-hydrophilic patterns achieved by
      coating a fraction of the NP sites with positive or negative charges via explicit
      solvent molecular dynamics simulations. Ten different charge pattern types
      including Janus charged-hydrophobic NPs are studied. The cationic NPs are more
      affected by the patterns and have higher diffusion constants and fluxes than
      their anionic NPs counterparts. The NP-water interaction dependence on surface
      pattern and field strength explains these observations. The NP-water Coulomb
      interaction of anionic NPs in the bulk, which are much stronger than the
      hydrophobic NP-water interactions, are stronger for NPs with higher localized
      charge, and stronger than in the cationic NPs counterparts. The diffusion and
      transport of anionic NPs such as proteins and protein charge ladders with the
      same total charge but different surface charge patterns are slowest for the
      highest localized charge pattern, which also adsorb strongest onto surfaces. Our
      model demonstrates the separation (by reverse osmosis, capillary electrophoresis,
      or chromatography) of cationic NPs, including proteins with equal net charge but
      different surface charge distributions.

PMID- 22400575
TI  - Langevin equations for competitive growth models.
AB  - Langevin equations for several competitive growth models in one dimension are
      derived. For models with crossover from random deposition (RD) to some correlated
      deposition (CD) dynamics, with small probability p of CD, the surface tension nu
      and the nonlinear coefficient lambda of the associated equations have linear
      dependence on p due solely to this random choice. However, they also depend on
      the regularized step functions present in the analytical representations of the
      CD, whose expansion coefficients scale with p according to the divergence of
      local height differences when p->0. The superposition of those scaling factors
      gives nu~p(2) for random deposition with surface relaxation (RDSR) as the CD, and
      nu~p, lambda~p(3/2) for ballistic deposition (BD) as the CD, in agreement with
      simulation and other scaling approaches. For bidisperse ballistic deposition
      (BBD), the same scaling of RD-BD model is found. The Langevin equation for the
      model with competing RDSR and BD, with probability p for the latter, is also
      constructed. It shows linear p dependence of lambda, while the quadratic
      dependence observed in previous simulations is explained by an additional
      crossover before the asymptotic regime. The results highlight the relevance of
      scaling of the coefficients of step function expansions in systems with steep
      surfaces, which is responsible for noninteger exponents in some p-dependent
      stochastic equations, and the importance of the physical correspondence of
      aggregation rules and equation coefficients.

PMID- 22400576
TI  - Dewetting of solid films with substrate-mediated evaporation.
AB  - The dewetting dynamics of an ultrathin film is studied in the presence of
      evaporation-or reaction-of adatoms on the substrate. KMC simulations are in good
      agreement with an analytical model with diffusion, rim facetting, and substrate
      sublimation. As sublimation is increased, we find a transition from the usual
      dewetting regime where the front slows down with time, to a sublimation
      controlled regime where the front velocity is approximately constant. The rim
      width exhibits an unexpected nonmonotonous behavior, with a maximum in time.

PMID- 22400577
TI  - Formation and ordering of topological defect arrays produced by dilatational
      strain and shear flow in smectic-A liquid crystals.
AB  - A microscale shear cell is used to study the formation of parabolic focal conic
      defects in the thermotropic smectic-A liquid crystal 8CB (4-octyl-4'
      cyanobiphenyl). Defects are produced by four distinct methods: by the application
      of dilatational strain alone, by shear flow alone, by dilatational strain and
      subsequent shear flow, and by the simultaneous application of dilatational strain
      and shear flow. We confirm that defects originate within the bulk, consistent
      with the previously suggested undulation instability mechanism. In the presence
      of a shear flow, we observe that defect formation requires micrometer-level
      dilatations, whose magnitude depends on the sample thickness. The size and
      ordering of both disordered and ordered defect arrays is quantified using a pair
      distribution function. Deviations from the predictions of linear stability theory
      are observed that have not been reported previously. For example, defects form a
      square array with greater ordering in the principal flow direction. Ordering due
      to shear flow does not change the average defect size. It has been shown
      previously that the principal defect sizes of ordered defects scale differently
      with sample thickness than the wavelength of the small amplitude undulations. We
      find that disordered defects show a similar deviation from this predicted
      wavelength.

PMID- 22400578
TI  - Viscoelasticity of ambient-temperature nematic binary mixtures of bent-core and
      rodlike molecules.
AB  - We report measurements of the temperature variations of physical parameters in
      ambient-temperature nematic liquid crystal mixtures of bent-core (BC) and rodlike
      molecules (5CB): birefringence Deltan; static dielectric constants epsilon(||)
      and epsilon(?); splay K(11) and bend K(33) elastic constants; rotational
      viscosity gamma(1); and diffusion coefficients D(||) and D(?) of a microsphere.
      Both Deltan and epsilon(||) decreases rapidly with increasing BC concentration,
      whereas epsilon(?) remains almost constant. At a shifted temperature (e.g., T
      T(NI)=-10  degrees C), K(11) increases by ~50% and K(33) decreases by ~80%
      compared to pure 5CB when the BC concentration is increased to ~43 mol % in the
      mixture. Viscosities parallel and perpendicular to the director, eta(||), eta(?),
      which are nearly equal to the Miesowicz viscosities eta(2) and eta(3),
      respectively, were obtained by D(||) and D(?) using the Stokes-Einstein relation.
      Both the viscosities at room temperature increase by 60 and 50 times,
      respectively, whereas gamma(1) increases by 180 times (at ~43 mol %) compared to
      the corresponding values of pure 5CB. The stiffening of K(11) and exorbitantly
      large enhancement in all the viscosities at a higher mol % of BC indicate that
      the viscoelastic properties are highly impacted by the presence of smectic
      clusters of BC molecules that results from the restricted free rotation of the
      molecules along the bow axis in the nematic phase. A possible attachment model of
      smectic type clusters of BC molecules surrounding the microparticle is presented.

PMID- 22400579
TI  - Negative Poisson's ratio and semisoft elasticity of smectic-C liquid-crystal
      elastomers.
AB  - Models of smectic-C liquid-crystal elastomers predict that they can display soft
      elasticity, in which the shape of the elastomer changes at no energy cost. The
      amplitude of the soft mode and the accompanying shears are dependent on the
      orientation of the layer normal and the director with respect to the stretch
      axis. We demonstrate that in some geometries the director is forced to rotate
      perpendicular to the stretch axis, causing lateral expansion of the sample-a
      negative Poisson's ratio. Current models do not include the effect of
      imperfections that must be present in the physical sample. We investigate the
      effect of a simple model of these imperfections on the soft modes in monodomain
      smectic-C elastomers in a variety of geometries. When stretching parallel to the
      layer normal (with imposed strain) the elastomer has a negative stiffness once
      the director starts to rotate. We show that this is a result of the negative
      Poisson's ratio in this geometry through a simple scalar model.

PMID- 22400580
TI  - Laser-induced holographic light scattering in a liquid-crystalline azobenzene
      containing polymer.
AB  - The holographic scattering phenomenon was observed and studied in detail for
      azobenzene-containing polymer system. It was found that irradiation of 25-MUm
      thick samples of the polymer with a single linearly polarized laser beam results
      in the appearance of a band with the maximum in the vicinity of irradiating
      wavelength in polarized extinction spectra. The band is completely polarized
      along the polarization direction of irradiating light. The shape of the band is
      exceedingly sensitive to rotation of the sample with respect to the spectrometer
      probe beam. An analogous band appears upon the irradiation of the sample with
      circularly polarized light. The observed phenomenon is presumably similar to
      holographic scattering, reported previously in photorefractive crystals and some
      photopolymers. A detailed description of the observed spectral changes is
      presented. The sensitivity of the effect towards probe light polarization and
      direction, irradiating light wavelength, and temperature is discussed.

PMID- 22400581
TI  - Voltage-induced defect mode coupling in a one-dimensional photonic crystal with a
      twisted-nematic defect layer.
AB  - Defect modes are investigated in a band gap of an electrically tunable one
      dimensional photonic crystal infiltrated with a twisted-nematic liquid crystal.
      Their frequency shift and interference under applied voltage are studied both
      experimentally and theoretically. We deal with the case where the defect layer
      thickness is much larger than the wavelength (i.e., the Mauguin condition). It is
      shown theoretically that the defect modes could have a complex structure with
      elliptic polarization. Two series of polarized modes are coupled with each other
      and exhibit an avoided crossing phenomenon in the case of opposite parity.

PMID- 22400582
TI  - Theory of elastic interaction between colloidal particles in a nematic cell in
      the presence of an external electric or magnetic field.
AB  - The Green's function method developed previously [S. B. Chernyshuk and B. I. Lev,
      Phys. Rev. E 81, 041701 (2010)] is used to describe elastic interactions between
      axially symmetric colloidal particles in a nematic cell in the presence of an
      external electric or magnetic field. Formulas for dipole-dipole, dipole
      quadrupole, and quadrupole-quadrupole interactions in the homeotropic and planar
      nematic cells with parallel and perpendicular field orientations are obtained. A
      set of predictions has been made: (1) The deconfinement effect for dipole
      particles in the homeotropic nematic cell when an electric field is approaching
      its Freedericksz threshold value E=>E(t). This means cancellation of the
      confinement effect found in [M. Vilfan et al., Phys. Rev. Lett. 101, 237801
      (2008)] near the Freedericksz transition. In the planar nematic cell this
      deconfinement effect exists for both dipole and quadrupole particles and depends
      on the field orientation as well as on the sign of dielectric anisotropy
      Deltaepsilon. (2) The effect of tunable stabilization of the particles is
      predicted. The equilibrium distance between two particles, which are attracted
      along the electric field parallel to the planes of a homeotropic nematic cell
      with Deltaepsilon<0, depends on the strength of the field. (3) Attraction and
      repulsion zones for all elastic interactions are changed dramatically under the
      action of the external field.

PMID- 22400583
TI  - Volume phase transitions of biaxial nematic elastomers.
AB  - We present a mean-field theory to describe biaxial nematic phases of side-chain
      liquid crystalline elastomers. Novel biaxial nematic phases are theoretically
      predicted in a side-chain liquid crystalline polymer and gel, where side chains
      (mesogens) and rigid-backbone chains favor mutually perpendicular orientations.
      We calculate uniaxial and biaxial orientational order parameters and examine
      deformations of the gel and stable biaxial nematic phases of the liquid
      crystalline gel dissolved in isotropic solvents. We predict first-order uniaxial
      biaxial nematic phase transitions of the gel and the volume of the gel is
      discontinuously changed at the phase transition temperature.

PMID- 22400584
TI  - Comparison of the kinetic friction of planar neutral and polyelectrolyte polymer
      brushes using molecular dynamics simulations.
AB  - We have simulated the relative shear motion of both neutral and polyelectrolyte
      end-grafted polymer brushes using molecular dynamics. The flexible neutral
      polymer brush is treated as a bead-spring model, and the polyelectrolyte brush is
      treated the same way except that each bead is charged and there are counterions
      present to neutralize the charge. We investigated the friction coefficient,
      monomer density, and brush penetration for both polyelectrolyte and neutral
      brushes with both equal grafting density and equal normal force under good
      solvent conditions. We found that polyelectrolyte brushes had a smaller friction
      coefficient and monomer penetration than neutral polymer brushes with the
      identical grafting density and chain length, and the polyelectrolyte brushes
      supported a much higher normal load than the neutral brushes for the same degree
      of compression. Charged and neutral brushes with their grafting densities chosen
      so that they support the same load exhibited approximately the same degree of
      interpenetration, but the polyelectrolyte brush exhibited a significantly lower
      friction coefficient. We present evidence that the reason for this is that the
      extra normal force contribution provided by the counterion osmotic pressure that
      exists for polyelectrolyte brushes permits them to support the same load as an
      identical neutral polymer brush of higher grafting density. Because of the
      resulting lower monomer density for the charged brushes, fewer monomer collisions
      take place per unit time, resulting in a lower friction coefficient.

PMID- 22400585
TI  - Noise effects in nonlinear biochemical signaling.
AB  - It has been generally recognized that stochasticity can play an important role in
      the information processing accomplished by reaction networks in biological cells.
      Most treatments of that stochasticity employ Gaussian noise even though it is a
      priori obvious that this approximation can violate physical constraints, such as
      the positivity of chemical concentrations. Here, we show that even when such
      nonphysical fluctuations are rare, an exact solution of the Gaussian model shows
      that the model can yield unphysical results. This is done in the context of a
      simple incoherent-feedforward model which exhibits perfect adaptation in the
      deterministic limit. We show how one can use the natural separation of time
      scales in this model to yield an approximate model, that is analytically
      solvable, including its dynamical response to an environmental change.
      Alternatively, one can employ a cutoff procedure to regularize the Gaussian
      result.

PMID- 22400586
TI  - Estimating the bending modulus of a FtsZ bacterial-division protein filament.
AB  - FtsZ, a cytoskeletal protein homologous to tubulin, is the principle constituent
      of the division ring in bacterial cells. It is known to have force-generating
      capacity in vitro and has been conjectured to be the source of the constriction
      force in vivo. Several models have been proposed to explain the generation of
      force by the Z ring. Here we re-examine data from in vitro experiments in which Z
      rings formed and constricted inside tubular liposomes, and we carry out image
      analysis on previously published data with which to better estimate important
      model parameters that have proven difficult to measure by direct means. We
      introduce a membrane-energy-based model for the dynamics of multiple Z rings
      moving and colliding inside a tubular liposome and a fluid model for the drag of
      a Z ring as it moves through the tube. Using this model, we estimate an effective
      membrane bending modulus of 500-700 pN nm. If we assume that FtsZ force
      generation is driven by hydrolysis into a highly curved conformation, we estimate
      the FtsZ filament bending modulus to be 310-390 pN nm(2). If we assume instead
      that force is generated by the non-hydrolysis-dependent intermediate curvature
      conformation, we find that B(f)>1400 pN nm(2). The former value sits at the lower
      end of the range of previously estimated values and, if correct, may raise
      challenges for models that rely on filament bending to generate force.

PMID- 22400587
TI  - Hierarchical fiber bundle model to investigate the complex architectures of
      biological materials.
AB  - The mechanics of fiber bundles has been widely studied in the literature, and
      fiber bundle models in particular have provided a wealth of useful analytical and
      numerical results for modeling ordinary materials. These models, however, are
      inadequate to treat bioinspired nanostructured materials, where hierarchy,
      multiscale, and complex properties play a decisive role in determining the
      overall mechanical characteristics. Here, we develop an ad hoc hierarchical
      theory designed to tackle these complex architectures, thus allowing the
      determination of the strength of macroscopic hierarchical materials from the
      properties of their constituents at the nanoscale. The roles of finite size,
      twisting angle, and friction are also included. Size effects on the statistical
      distribution of fiber strengths naturally emerge without invoking best-fit or
      unknown parameters. A comparison between the developed theory and various
      experimental results on synthetic and natural materials yields considerable
      agreement.

PMID- 22400588
TI  - Cellular ability to sense spatial gradients in the presence of multiple
      competitive ligands.
AB  - Many eukaryotic and prokaryotic cells can exhibit remarkable sensing ability
      under small gradients of chemical compounds. In this study, we approach this
      phenomenon by considering the contribution of multiple ligands to the chemical
      kinetics within the Michaelis-Menten model. This work was inspired by the recent
      theoretical findings of Hu et al. [Phys. Rev. Lett. 105, 048104 (2010)]. Our
      treatment with practical binding energies and chemical potentials provides
      results that are consistent with experimental observations.

PMID- 22400589
TI  - Magnetic nanomanipulations inside living cells compared with passive tracking of
      nanoprobes to get consensus for intracellular mechanics.
AB  - During the last decade, the development of nanomaterials to penetrate inside
      living cells has been the focus of a large number of studies, with applications
      for the biomedical field. However, the further dynamics of these nanomaterials
      inside the cells is dictated by the intracellular environment and in particular
      its mechanical properties. The mechanical characteristics of the cell interior
      can be probed with either active or passive microrheological approaches. However,
      active intracellular microrheology is still in its infancy, owing to the
      difficulty of inserting probes that can be manipulated by external forces. Here
      we review recent active microrheology studies using magnetic nanoprobes inserted
      into endosomes or phagosomes as useful approaches for measuring frequency
      dependent viscoelasticity, for mapping the viscoelastic landscape, as well as for
      identifying the contribution of individual cytoskeleton components and the
      influence of cell motility. The results of such direct measurements challenge the
      validity of more typical passive approaches in which the spontaneous displacement
      of embedded nanoprobes is measured. Here we discuss that one must distinguish
      probes suitable for use in conditions of thermal equilibrium, whose movements
      reflect the mechanical environment from probes that interact actively with the
      cytoplasm and cytoskeleton, in a state of nonequilibrium for which fluctuation
      dissipation theorem no longer holds. However, when data on these probes'
      viscoelastic microenvironment is available, such passive probe movements can
      yield useful information on the forces responsible for intracellular activity.

PMID- 22400590
TI  - Dynamic structure factor of vibrating fractals: proteins as a case study.
AB  - We study the dynamic structure factor S(k,t) of proteins at large wave numbers k,
      kR(g)?1, where R(g) is the gyration radius. At this regime measurements are
      sensitive to internal dynamics, and we focus on vibrational dynamics of folded
      proteins. Exploiting the analogy between proteins and fractals, we perform a
      general analytic calculation of the displacement two-point correlation functions,
      <[u(->)(i)(t)-u(->)(j)(0)](2)>. We confront the derived expressions with
      numerical evaluations that are based on protein data bank (PDB) structures and
      the Gaussian network model (GNM) for a few proteins and for the Sierpinski gasket
      as a controlled check. We use these calculations to evaluate S(k,t) with arrested
      rotational and translational degrees of freedom, and show that the decay of
      S(k,t) is dominated by the spatially averaged mean-square displacement of an
      amino acid. The latter has been previously shown to evolve subdiffusively in
      time, <[u(->)(i)(t)-u(->)(i)(0)](2)> ~t(nu), where nu is the anomalous diffusion
      exponent that depends on the spectral dimension d(s) and fractal dimension d(f).
      As a result, for wave numbers obeying k(2)<u(->)(2)>?1, S(k,t) effectively decays
      as a stretched exponential S(k,t)?S(k)e(-(Gamma(k)t)(beta)) with beta?nu, where
      the relaxation rate is Gamma(k)~(k(B)T/momega(o)(2))(1/beta)k(2/beta), T is the
      temperature, and momega(o)(2) the GNM effective spring constant describing the
      interaction between neighboring amino acids. The static structure factor is
      dominated by the fractal character of the native fold, S(k)~k(-d(f)), with
      negligible to marginal influence of vibrations. The analytical expressions are
      first confronted with numerically based calculations on the Sierpinski gasket,
      and very good agreement is found between simulations and theory. We then perform
      PDB-GNM-based numerical calculations for a few proteins, and an effective
      stretched exponential decay of the dynamic structure factor is found, albeit
      their relatively small size. However, when rotational and translational diffusion
      are added, we find that their contribution is never negligible due to finite size
      effects. While we can still attribute an effective stretching exponent beta to
      the relaxation profile, this exponent is significantly larger than the anomalous
      diffusion exponent nu. We compare our theory with recent neutron spin-echo
      studies of myoglobin and hemoglobin and conclude that experiments in which the
      rotational and translational degrees of freedom are arrested, e.g., by anchoring
      the proteins to a surface, will improve the detection of internal vibrational
      dynamics.

PMID- 22400591
TI  - Photonic polycrystal in the greenish-white scales of the African longhorn beetle
      Prosopocera lactator (Cerambycidae).
AB  - Three-dimensional photonic-crystal grains were found in the scales of the
      longhorn beetle Prosopocera lactator (Cerambycidae). The local geometric
      structure can be described as a face-centered-cubic array of spheres, connected
      by short rods, reminiscent of the "ball-and-stick" models used by solid-state
      chemists to visualize atomic structures. Based on scanning electron microscopy, x
      ray nanotomography, optical measurements, photonic band-structure calculations,
      and computer simulations of the reflectance, the desaturated greenish coloration
      is shown to arise from the observed photonic polycrystalline structure. X-ray
      nanotomography is revealed as a very promising tool for photonic-crystal
      morphology studies.

PMID- 22400592
TI  - Competition between curls and plectonemes near the buckling transition of
      stretched supercoiled DNA.
AB  - Recent single-molecule experiments have observed that formation of a
      plectonemically supercoiled region in a stretched, twisted DNA proceeds via
      abrupt formation of a small plectonemic "bubble." A detailed mesoscopic model is
      presented for the formation of plectonemic domains, including their positional
      entropy, and the influence of small chiral loops or "curls" along the extended
      DNA. Curls begin to appear just before plectoneme formation, and are more
      numerous at low salt concentrations (<20 mM univalent ions) and at low forces
      (<0.5 pN). However, plectonemic domains quickly become far more stable slightly
      beyond the transition to supercoiling at moderate forces and physiological salt
      conditions. At the supercoiling transition, for shorter DNAs (2 kb) only one
      supercoiled domain appears, but for longer DNAs at lower forces (<0.5 pN)
      positional entropy favors formation of more than one plectonemic domain; a
      similar effect occurs for low salt. Although they are not the prevalent mode of
      supercoiling, curls are a natural transition state for binding of DNA-loop
      trapping enzymes; we show how addition of loop-trapping enzymes can modify the
      supercoiling transition. The behavior of DNA torque is also discussed, including
      the effect of the measurement apparatus torque stiffness, which can play a role
      in determining how large the torque "overshoot" is at the buckling transition.

PMID- 22400593
TI  - Propagating unstable wavelets in cardiac tissue.
AB  - Solitonlike propagating modes have been proposed for excitable tissue, but have
      never been measured in cardiac tissue. In this study, we simulate an experimental
      protocol to elicit these propagating unstable wavelets (PUWs) in a detailed three
      dimensional ventricular wedge preparation. PUWs appear as fixed-shape wavelets
      that propagate only in the direction of cardiac fibers, with conduction velocity
      approximately 40% slower than normal action potential excitation. We investigate
      their properties, demonstrating that PUWs are not true solitons. The range of
      stimuli for which PUWs were elicited was very narrow (several orders of magnitude
      lower than the stimulus strength itself), but increased with reduced sodium
      conductance and reduced coupling in nonlongitudinal directions. We show that the
      phenomenon does not depend on the particular membrane representation used or the
      shape of the stimulating electrode.

PMID- 22400594
TI  - Corticothalamic dynamics: structure of parameter space, spectra, instabilities,
      and reduced model.
AB  - Linear instabilities are analyzed in a physiologically based mean-field
      corticothalamic model and a reduced-parameter model derived from it. In both
      models, the stable zone corresponding to normal arousal states is bounded by a
      series of surfaces demarcating the onsets of instabilities. The stable zone is
      found to depend on delay and rate parameters, whose values have a simple
      relationship to the number of instabilities and dominant frequencies on the
      stable zone's boundary. The dominant frequencies of linear activity inside the
      stable zone are found to lie in clearly delineated regions, each corresponding to
      an instability surface on its boundary and having approximately the same dominant
      frequency. These regions are ordered in parameter space according to their
      dominant frequencies, and an instability associated with the intrathalamic loop
      is shown to have the highest frequency that can become unstable. This reveals an
      important role for the thalamus in controlling the stability and bandwidth of
      dynamics in the corticothalamic system as a whole. The reduced model is found to
      agree well with the full model in a wide region of parameter space and, thus, is
      a useful guide to the full model's dynamics.

PMID- 22400595
TI  - Statistical physics approach to dendritic computation: the excitable-wave mean
      field approximation.
AB  - We analytically study the input-output properties of a neuron whose active
      dendritic tree, modeled as a Cayley tree of excitable elements, is subjected to
      Poisson stimulus. Both single-site and two-site mean-field approximations
      incorrectly predict a nonequilibrium phase transition which is not allowed in the
      model. We propose an excitable-wave mean-field approximation which shows good
      agreement with previously published simulation results [Gollo et al., PLoS
      Comput. Biol. 5, e1000402 (2009)] and accounts for finite-size effects. We also
      discuss the relevance of our results to experiments in neuroscience, emphasizing
      the role of active dendrites in the enhancement of dynamic range and in gain
      control modulation.

PMID- 22400596
TI  - Interrelating anatomical, effective, and functional brain connectivity using
      propagators and neural field theory.
AB  - It is shown how to compute effective and functional connection matrices (eCMs and
      fCMs) from anatomical CMs (aCMs) and corresponding strength-of-connection
      matrices (sCMs) using propagator methods in which neural interactions play the
      role of scatterings. This analysis demonstrates how network effects dress the
      bare propagators (the sCMs) to yield effective propagators (the eCMs) that can be
      used to compute the covariances customarily used to define fCMs. The results
      incorporate excitatory and inhibitory connections, multiple structures and
      populations, asymmetries, time delays, and measurement effects. They can also be
      postprocessed in the same manner as experimental measurements for direct
      comparison with data and thereby give insights into the role of coarse-graining,
      thresholding, and other effects in determining the structure of CMs. The
      spatiotemporal results show how to generalize CMs to include time delays and how
      natural network modes give rise to long-range coherence at resonant frequencies.
      The results are demonstrated using tractable analytic cases via neural field
      theory of cortical and corticothalamic systems. These also demonstrate close
      connections between the structure of CMs and proximity to critical points of the
      system, highlight the importance of indirect links between brain regions and
      raise the possibility of imaging specific levels of indirect connectivity. Aside
      from the results presented explicitly here, the expression of the connections
      among aCMs, sCMs, eCMs, and fCMs in terms of propagators opens the way for
      propagator theory to be further applied to analysis of connectivity.

PMID- 22400598
TI  - Evolution and stability of altruist strategies in microbial games.
AB  - When microbes compete for limited resources, they often engage in chemical
      warfare using bacterial toxins. This competition can be understood in terms of
      evolutionary game theory (EGT). We study the predictions of EGT for the bacterial
      "suicide bomber" game in terms of the phase portraits of population dynamics, for
      parameter combinations that cover all interesting games for two-players, and
      seven of the 38 possible phase portraits of the three-player game. We compare
      these predictions to simulations of these competitions in finite well-mixed
      populations, but also allowing for probabilistic rather than pure strategies, as
      well as Darwinian adaptation over tens of thousands of generations. We find that
      Darwinian evolution of probabilistic strategies stabilizes games of the rock
      paper-scissors type that emerge for parameters describing realistic bacterial
      populations, and point to ways in which the population fixed point can be
      selected by changing those parameters.

PMID- 22400597
TI  - Contractile network models for adherent cells.
AB  - Cells sense the geometry and stiffness of their adhesive environment by active
      contractility. For strong adhesion to flat substrates, two-dimensional
      contractile network models can be used to understand how force is distributed
      throughout the cell. Here we compare the shape and force distribution for
      different variants of such network models. In contrast to Hookean networks, cable
      networks reflect the asymmetric response of biopolymers to tension versus
      compression. For passive networks, contractility is modeled by a reduced resting
      length of the mechanical links. In actively contracting networks, a constant
      force couple is introduced into each link in order to model contraction by
      molecular motors. If combined with fixed adhesion sites, all network models lead
      to invaginated cell shapes, but only actively contracting cable networks lead to
      the circular arc morphology typical for strongly adhering cells. In this case,
      shape and force distribution are determined by local rather than global
      determinants and thus are suited to endow the cell with a robust sense of its
      environment. We also discuss nonlinear and adaptive linker mechanics as well as
      the relation to tissue shape.

PMID- 22400599
TI  - Phase transitions in predator-prey systems.
AB  - The relationship between predator and prey plays an important role in ecosystem
      conservation. However, our understanding of the principles underlying the spatial
      distribution of predators and prey is still poor. Here we present a phase diagram
      of a predator-prey system and investigate the lattice formation in such a system.
      We show that the production of stable lattice structures depends on the limited
      diffusion or migration of prey as well as higher carrying capacity for the prey.
      In addition, when the prey's growth rate is lower than the birth rate of the
      predator, global prey lattice formation is initiated by microlattices at the
      center of prey spirals. The predator lattice is later formed in the predator
      spirals. But both lattice formations proceed together as the prey growth rate
      increases.

PMID- 22400600
TI  - Compact-envelope bright solitary wave in a DNA double strand.
AB  - We study the nonlinear dynamics of a homogeneous DNA chain that is based on site
      dependent finite stacking and pairing enthalpies. We introduce an extended
      nonlinear Schrodinger equation describing the dynamics of modulated wave in DNA
      model. We obtain envelope bright solitary waves with compact support as a
      solution. Analytical criteria of existence of this solution are derived. The
      stability of bright compactons is confirmed by numerical simulations of the exact
      equations of the lattice. The impact of the finite stacking energy is
      investigated, and we show that some of these compact bright solitary waves are
      robust, while others decompose very quickly depending on the finite stacking
      parameters.

PMID- 22400601
TI  - Signal transduction across cellular membranes can be mediated by coupling of the
      clustering of anchored proteins in both leaflets.
AB  - One key question in signal transduction is how the signal is relayed from the
      outer leaflet of a cellular membrane to the inner leaflet. Using a simulation
      model, a mechanism for the mediation of signal transduction is proposed here in
      which the coupling between membrane proteins in different leaflets can be
      achieved by the clustering of anchored proteins, without recruiting transmembrane
      proteins. Depending on the hydrophobic length of the anchored proteins, three
      coupling patterns, including face-to-face clustering, interdigitated clustering,
      and weak-coupled clustering, are observed in this work. This observation provides
      a possible explanation of how a particular downstream signaling pathway is
      selected.

PMID- 22400602
TI  - Growth dynamics of cancer cell colonies and their comparison with noncancerous
      cells.
AB  - The two-dimensional (2D) growth dynamics of HeLa (cervix cancer) cell colonies
      was studied following both their growth front and the pattern morphology
      evolutions utilizing large population colonies exhibiting linearly and radially
      spreading fronts. In both cases, the colony profile fractal dimension was
      d(f)=1.20+/-0.05 and the growth fronts displaced at the constant velocity 0.90+/
      0.05 MUm min(-1). Colonies showed changes in both cell morphology and average
      size. As time increased, the formation of large cells at the colony front was
      observed. Accordingly, the heterogeneity of the colony increased and local
      driving forces that set in began to influence the dynamics of the colony front.
      The dynamic scaling analysis of rough colony fronts resulted in a roughness
      exponent alpha = 0.50+/-0.05, a growth exponent beta = 0.32+/-0.04, and a dynamic
      exponent z=1.5+/-0.2. The validity of this set of scaling exponents extended from
      a lower cutoff l(c)~60 MUm upward, and the exponents agreed with those predicted
      by the standard Kardar-Parisi-Zhang continuous equation. HeLa data were compared
      with those previously reported for Vero cell colonies. The value of d(f) and the
      Kardar-Parisi-Zhang-type 2D front growth dynamics were similar for colonies of
      both cell lines. This indicates that the cell colony growth dynamics is
      independent of the genetic background and the tumorigenic nature of the cells.
      However, one can distinguish some differences between both cell lines during the
      growth of colonies that may result from specific cooperative effects and the
      nature of each biosystem.

PMID- 22400603
TI  - Flexural fracturing of a cohesive granular layer.
AB  - We report on the fracturing of cohesive granular materials subjected to a
      flexural deformation. A thin layer of glass beads or of flour is deposited on an
      unstretchable membrane to which flexion is imposed. We observe the formation of a
      periodic fracturing pattern whose characteristics are discussed in comparison
      with results previously obtained for an in-plane stretching [Alarcon, Ramos,
      Vanel, Vittoz, Melo, and Geminard, Phys. Rev. Lett. 105, 208001 (2010)]. In
      particular, at a given relative humidity, the wavelength is observed to depend
      linearly on the layer thickness but to be independent of the grain size, although
      the smallest grains are clearly more cohesive.

PMID- 22400604
TI  - Relaxation creep rupture of heterogeneous material under constant strain.
AB  - We focus on a system consisting of an elastic part and a damageable part in
      series, to study the relaxation creep rupture of a heterogeneous system subjected
      to a uniaxial constant strain applied instantaneously. The viscoelastic behavior
      of the damageable part is modeled by a fiber bundle model consisting of Kelvin
      Voigt elements and global load sharing is assumed for the redistribution of load
      following fiber breaking in the damageable part. Analytical and numerical
      calculations show that the global relaxation creep rupture appears if the elastic
      energy stored in the elastic part exceeded the fracture energy of the damageable
      part. The lifetime of the system strongly depends on the values of the applied
      external strain and the initial stiffness ratio k between the elastic part and
      the damageable part. We show that a higher stiffness ratio implies a more brittle
      system. Prior to complete failure, relaxation creep rupture exhibits a sequence
      of three stages, similar to creep rupture under constant stress, and the nominal
      force rate presents a power law singularity with a power index -1/2 near the
      global rupture time.

PMID- 22400605
TI  - Electric-double-layer potential distribution in multiple-layer immiscible
      electrolytes: effect of finite ion sizes.
AB  - In a recent study [S. Das and S. Hardt, Phys. Rev. E 84, 022502 (2011).], we
      provided analytical results for the electric-double-layer (EDL) electrostatic
      potential distribution in a system of immiscible electrolyte layers confined
      between plates with gap dimensions comparable to the EDL thickness. We
      demonstrated that the intrinsic jumps in the ion-solvent interactions across the
      interface of the immiscible electrolytes lead to nontrivial electrostatic
      potential distributions that may completely defy or substantially augment the
      effect of the boundary wall potential. In this Brief Report, I extend this
      calculation to obtain analytical and numerical results for the case with finite
      ion sizes (or a finite ionic steric effect). It is found that the finite steric
      effect substantially enhances the contributions of jump in the ion-solvent
      interactions in the overall electrostatic potential distribution. More
      importantly, I demonstrate that such jumps in the ion-solvent interactions, owing
      to the immiscibility of the electrolytes, ensure that even for very weak wall
      zeta potentials, the steric effect can significantly affect the electrostatic
      potential distribution.

PMID- 22400606
TI  - Flexoelectric and elastic coefficients of odd and even homologous bimesogens.
AB  - It is known that bimesogenic liquid crystals exhibit a marked "odd-even" effect
      in the flexoelastic ratio (the effective flexoelectric coefficient to the average
      elastic coefficient), with the ratio being higher for the "odd-spaced" bimesogens
      (those with an odd number of alkyl groups in the spacer chain) than their
      neighboring even-spaced counterparts. To determine the contribution of each
      property to the flexoelastic ratio, we present experimental results on the
      flexoelectric and elastic coefficients of two homologous nonsymmetric bimesogens
      which possess odd and even alkyl spacers. Our results show that, although there
      are differences in the flexoelectric coefficients, there are substantially larger
      differences in the effective elastic coefficient. Specifically, the odd bimesogen
      is found to have both a low splay elastic coefficient and a very low bend elastic
      coefficient which, when combined, results in a significantly lower effective
      elastic coefficient and consequently a higher flexoelastic ratio.

PMID- 22400607
TI  - Defect modeling in spreading nematic droplets.
AB  - Experiments by Poulard and Cazabat [Langmuir 21, 6270 (2005)] on spreading
      droplets of nematic liquid crystal (NLC) reveal a surprisingly rich variety of
      behavior, including at least two different emerging length scales resulting from
      a contact line instability. In earlier work [Cummings, Lin, and Kondic, Phys.
      Fluids 23, 043102 (2011)] we modified a lubrication model for NLCs due to Ben
      Amar and Cummings [Phys. Fluids 13, 1160 (2001)] and showed that, in a
      qualitative sense, it can account for two-dimensional (2D) versions of the
      observed behavior. In the present work we propose a different approach that
      allows us to explore the effect of anchoring variations on the substrate, again
      in a 2D geometry. This in turn gives a simple way to model the presence of
      defects, which are nearly always present in such flows. The present model leads
      to additional terms in the governing equation. We explore the influence of these
      additional terms for some simple flow scenarios to gain insight into their
      influence.

PMID- 22400608
TI  - Monte Carlo simulation-based approach to model the size distribution of
      metastatic tumors.
AB  - The size distribution of metastatic tumors and its time evolution are
      traditionally described by integrodifferential equations and stochastic models.
      Here we develop a simple Monte Carlo approach in which each event of metastasis
      is treated as a chance event through random-number generation. We demonstrate the
      accuracy of this approach on a specific growth and metastasis model by showing
      that it quantitatively reproduces the size distribution and the total number of
      tumors as a function of time. The approach also yields statistical distribution
      of patient-to-patient variations, and has the flexibility to incorporate many
      real-life complexities.

PMID- 22400609
TI  - Decelerated spreading in degree-correlated networks.
AB  - While degree correlations are known to play a crucial role for spreading
      phenomena in networks, their impact on the propagation speed has hardly been
      understood. Here we investigate a tunable spreading model on scale-free networks
      and show that the propagation becomes slow in positively (negatively) correlated
      networks if nodes with a high connectivity locally accelerate (decelerate) the
      propagation. Examining the efficient paths offers a coherent explanation for this
      result, while the k-core decomposition reveals the dependence of the nodal
      spreading efficiency on the correlation. Our findings should open new pathways to
      delicately control real-world spreading processes.

PMID- 22400610
TI  - Differences between emission patterns and internal modes of optical resonators.
AB  - The evanescent wave field outside an optical resonator is typically strongly
      directional when the shape deviates even very slightly from being perfectly
      circular or spherical. In this Rapid Communication we show that the tunneling
      mechanism underlying escape from such weakly deformed resonators can lead to
      emission patterns that look quite different to the corresponding internal mode. A
      direct short-wavelength analysis is not possible because the required complex ray
      data cannot be found due to the presence of natural boundaries. We show, however,
      that an approach based on perturbative approximation of the ray families
      successfully describes this phenomenon. In appropriate limits, the emission
      pattern allows one effectively to perform a direct observation of solutions of
      the one-dimensional Schrodinger equation in the complex plane.

PMID- 22400611
TI  - First-principles model of time-dependent variations in transmission through a
      fluctuating scattering environment.
AB  - Fading is the time-dependent variation in transmitted signal strength through a
      complex medium due to interference or temporally evolving multipath scattering.
      In this paper we use random matrix theory (RMT) to establish a first-principles
      model for fading, including both universal and nonuniversal effects. This model
      provides a more general understanding of the most common statistical models
      (Rayleigh fading and Rice fading) and provides a detailed physical basis for
      their parameters. We also report experimental tests on two ray-chaotic microwave
      cavities. The results show that our RMT model agrees with the Rayleigh and Rice
      models in the high-loss regime, but there are strong deviations in low-loss
      systems where the RMT approach describes the data well.

PMID- 22400612
TI  - Fast numerical test of hyperbolic chaos.
AB  - An effective numerical method for testing the hyperbolicity of chaotic dynamics
      is suggested. The method employs ideas of algorithms for covariant Lyapunov
      vectors but avoids their explicit computation. The outcome is a distribution of a
      characteristic value which is bounded within the unit interval and whose zero
      indicates a tangency between expanding and contracting subspaces. To perform the
      test one has to solve several copies of equations for infinitesimal perturbations
      whose number is equal to the sum of numbers of positive and zero Lyapunov
      exponents. Since this number is normally much less than the full phase space
      dimension, this method provides a fast and memory saving way for numerical
      hyperbolicity testing.

PMID- 22400613
TI  - Experiments on oscillator ensembles with global nonlinear coupling.
AB  - We experimentally analyze collective dynamics of a population of 20 electronic
      Wien-bridge limit-cycle oscillators with a nonlinear phase-shifting unit in the
      global feedback loop. With an increase in the coupling strength we first observe
      formation and then destruction of a synchronous cluster, so that the dependence
      of the order parameter on the coupling strength is not monotonic. After
      destruction of the cluster the ensemble remains nevertheless coherent, i.e., it
      exhibits an oscillatory collective mode (mean field). We show that the system is
      now in a self-organized quasiperiodic state, predicted in Rosenblum and Pikovsky
      [Phys. Rev. Lett. 98, 064101 (2007)]. In this state, frequencies of all
      oscillators are smaller than the frequency of the mean field, so that the
      oscillators are not locked to the mean field they create and their dynamics is
      quasiperiodic. Without a nonlinear phase-shifting unit, the system exhibits a
      standard Kuramoto-like transition to a fully synchronous state. We demonstrate a
      good correspondence between the experiment and previously developed theory. We
      also propose a simple measure which characterizes the macroscopic incoherence
      coherence transition in a finite-size ensemble.

PMID- 22400614
TI  - Noise can induce explosions for dissipative solitons.
AB  - We study the influence of noise on the spatially localized, temporally regular
      states (stationary, one frequency, two frequencies) in the regime of anomalous
      dispersion for the cubic-quintic complex Ginzburg-Landau equation as a function
      of the bifurcation parameter. We find that noise of a fairly small strength eta
      is sufficient to reach a chaotic state with exploding dissipative solitons. That
      means that noise can induce explosions over a fairly large range of values of the
      bifurcation parameter MU. Three different routes to chaos with exploding
      dissipative solitons are found as a function of MU. As diagnostic tools we use
      the separation to characterize chaotic behavior and the energy to detect
      spatially localized explosive behavior as a function of time.

PMID- 22400615
TI  - Nelkin scaling for the Burgers equation and the role of high-precision
      calculations.
AB  - Nelkin scaling, the scaling of moments of velocity gradients in terms of the
      Reynolds number, is an alternative way of obtaining inertial-range information.
      It is shown numerically and theoretically for the Burgers equation that this
      procedure works already for Reynolds numbers of the order of 100 (or even lower
      when combined with a suitable extended self-similarity technique). At moderate
      Reynolds numbers, for the accurate determination of scaling exponents, it is
      crucial to use higher than double precision. Similar issues are likely to arise
      for three-dimensional Navier-Stokes simulations.

PMID- 22400616
TI  - Inverse cascade of magnetic helicity in magnetohydrodynamic turbulence.
AB  - The nonlinear dynamics of magnetic helicity HM, which is responsible for large
      scale magnetic structure formation in electrically conducting turbulent media, is
      investigated in forced and decaying three-dimensional magnetohydrodynamic
      turbulence. This is done with the help of high-resolution direct numerical
      simulations and statistical closure theory. The numerically observed spectral
      scaling of HM is at variance with earlier work using a statistical closure model
      [Pouquet et al., J. Fluid Mech. 77, 321 (1976)]. By revisiting this theory, a
      universal dynamical balance relation is found that includes the effects of
      kinetic helicity as well as kinetic and magnetic energies on the inverse cascade
      of HM and explains the above-mentioned discrepancy. Consideration of the result
      in the context of mean-field dynamo theory suggests a nonlinear modification of
      the alpha-dynamo effect, which is important in the context of magnetic-field
      excitation in turbulent plasmas.

PMID- 22400617
TI  - High-speed jetting and spray formation from bubble collapse.
AB  - A method to create impacting jets at the micrometer length scale by means of a
      collapsing cavitation bubble is presented. A focused shock wave from a
      lithotripter leads to the nucleation of a cavitation bubble below a hole of 25
      MUm diameter etched in a silicon plate. The plate is placed at an air-water
      interface. The expansion and collapse of the bubble leads to two separate jets-
      an initial slow jet of velocity ~10 m/s and a later faster jet of velocity ~50
      m/s. The jets subsequently impact coaxially, resulting in a circular sheet of
      liquid in the plane perpendicular to their axis. The sheet is characterized by a
      ring of droplets at its rim and breaks up into a spray as the shock pressure is
      increased. The results demonstrate an approach to create a high-speed jet and
      fine spray on demand at the micrometer scale.

PMID- 22400618
TI  - Experimental evidence of reaction-driven miscible viscous fingering.
AB  - An experimental demonstration of reaction-driven viscous fingering developing
      when a more viscous solution of a reactant A displaces a less viscous miscible
      solution of another reactant B is presented. In the absence of reaction, such a
      displacement of one fluid by another less mobile one is classically stable.
      However, a simple A+B->C reaction can destabilize this interface if the product C
      is either more or less viscous than both reactant solutions. Using the pH
      dependence of the viscosity of some polymer solutions, we provide experimental
      evidence of both scenarios. We demonstrate quantitatively that reactive viscous
      fingering results from the buildup in time of nonmonotonic viscosity profiles
      with patterns behind or ahead of the reaction zone, depending on whether the
      product is more or less viscous than the reactants. The experimental findings are
      backed up by numerical simulations.

PMID- 22400619
TI  - Replica inference approach to unsupervised multiscale image segmentation.
AB  - We apply a replica-inference-based Potts model method to unsupervised image
      segmentation on multiple scales. This approach was inspired by the statistical
      mechanics problem of "community detection" and its phase diagram. Specifically,
      the problem is cast as identifying tightly bound clusters ("communities" or
      "solutes") against a background or "solvent." Within our multiresolution
      approach, we compute information-theory-based correlations among multiple
      solutions ("replicas") of the same graph over a range of resolutions. Significant
      multiresolution structures are identified by replica correlations manifest by
      information theory overlaps. We further employ such information theory measures
      (such as normalized mutual information and variation of information),
      thermodynamic quantities such as the system entropy and energy, and dynamic
      measures monitoring the convergence time to viable solutions as metrics for
      transitions between various solvable and unsolvable phases. Within the solvable
      phase, transitions between contending solutions (such as those corresponding to
      segmentations on different scales) may also appear. With the aid of these
      correlations as well as thermodynamic measures, the phase diagram of the
      corresponding Potts model is analyzed at both zero and finite temperatures.
      Optimal parameters corresponding to a sensible unsupervised segmentations appear
      within the "easy phase" of the Potts model. Our algorithm is fast and shown to be
      at least as accurate as the best algorithms to date and to be especially suited
      to the detection of camouflaged images.

PMID- 22400620
TI  - Optimized reduction of uncertainty in bursty human dynamics.
AB  - Human dynamics is known to be inhomogeneous and bursty but the detailed
      understanding of the role of human factors in bursty dynamics is still lacking.
      In order to investigate their role we devise an agent-based model, where an agent
      in an uncertain situation tries to reduce the uncertainty by communicating with
      information providers while having to wait time for responses. Here the waiting
      time can be considered as cost. We show that the optimal choice of the waiting
      time under uncertainty gives rise to the bursty dynamics, characterized by the
      heavy tailed distribution of optimal waiting time. We find that in all cases the
      efficiency for communication is relevant to the scaling behavior of the optimal
      waiting time distribution. On the other hand, the cost turns out in some cases to
      be irrelevant depending on the degree of uncertainty and efficiency.

PMID- 22400621
TI  - Epidemic threshold and control in a dynamic network.
AB  - In this paper we present a model describing susceptible-infected-susceptible-type
      epidemics spreading on a dynamic contact network with random link activation and
      deletion where link activation can be locally constrained. We use and adapt an
      improved effective degree compartmental modeling framework recently proposed by
      Lindquist et al. [J. Math Biol. 62, 143 (2010)] and Marceau et al. [Phys. Rev. E
      82, 036116 (2010)]. The resulting set of ordinary differential equations (ODEs)
      is solved numerically, and results are compared to those obtained using
      individual-based stochastic network simulation. We show that the ODEs display
      excellent agreement with simulation for the evolution of both the disease and the
      network and are able to accurately capture the epidemic threshold for a wide
      range of parameters. We also present an analytical R0 calculation for the dynamic
      network model and show that, depending on the relative time scales of the network
      evolution and disease transmission, two limiting cases are recovered: (i) the
      static network case when network evolution is slow and (ii) homogeneous random
      mixing when the network evolution is rapid. We also use our threshold calculation
      to highlight the dangers of relying on local stability analysis when predicting
      epidemic outbreaks on evolving networks.

PMID- 22400622
TI  - Rules and limitations of building delay-tolerant topologies for coupled systems.
AB  - This paper investigates the equilibrium behavior of broadly studied
      synchronization dynamics of coupled systems, among which shared information is
      delayed. The underlying relationship is established between graph structures and
      the largest amount of delay the dynamics can withstand without losing stability.
      In particular, based on Cartesian product of graphs, we present the rules and
      limitations for synthesizing the graphs of large-scale systems that can remain
      stable for as large delays as possible. Examples are provided to demonstrate the
      results.

PMID- 22400623
TI  - Time-delayed autosynchronous swarm control.
AB  - In this paper a general Morse potential model of self-propelling particles is
      considered in the presence of a time-delayed term and a spring potential. It is
      shown that the emergent swarm behavior is dependent on the delay term and weights
      of the time-delayed function, which can be set to induce a stationary swarm, a
      rotating swarm with uniform translation, and a rotating swarm with a stationary
      center of mass. An analysis of the mean field equations shows that without a
      spring potential the motion of the center of mass is determined explicitly by a
      multivalued function. For a nonzero spring potential the swarm converges to a
      vortex formation about a stationary center of mass, except at discrete
      bifurcation points where the center of mass will periodically trace an ellipse.
      The analytical results defining the behavior of the center of mass are shown to
      correspond with the numerical swarm simulations.

PMID- 22400624
TI  - Analytical and belief-propagation studies of random constraint satisfaction
      problems with growing domains.
AB  - We study solution-space structure and solution-finding algorithms of a
      representative hard random constraint satisfaction problem with growing domains
      known as Model RB. Using rigorous methods, we show that solutions are grouped
      into disconnected clusters before the theoretical satisfiability phase transition
      point. Using the cavity method, it is shown that the entropy density obtained by
      belief propagation (BP) on random Model RB instances, which corresponds well to
      the analytical results, vanishes as the control parameter (constraint tightness)
      approaches the satisfiability threshold. From an algorithmic point of view, we
      find that reinforced BP, which performs much better than all existing algorithms,
      allows us to find solutions efficiently for instances in the regime that is very
      close to the satisfiability transition. These results also can shed light on the
      effectiveness of BP reinforcement on problems with a large number of states.

PMID- 22400625
TI  - Supercooperation in evolutionary games on correlated weighted networks.
AB  - In this work we study the behavior of classical two-person, two-strategies
      evolutionary games on a class of weighted networks derived from Barabasi-Albert
      and random scale-free unweighted graphs. Using customary imitative dynamics, our
      numerical simulation results show that the presence of link weights that are
      correlated in a particular manner with the degree of the link end points leads to
      unprecedented levels of cooperation in the whole games' phase space, well above
      those found for the corresponding unweighted complex networks. We provide
      intuitive explanations for this favorable behavior by transforming the weighted
      networks into unweighted ones with particular topological properties. The
      resulting structures help us to understand why cooperation can thrive and also
      give ideas as to how such supercooperative networks might be built.

PMID- 22400626
TI  - Theory of correlation in a network with synaptic depression.
AB  - Synaptic depression affects not only the mean responses of neurons but also the
      correlation of response variability in neural populations. Although previous
      studies have constructed a theory of correlation in a spiking neuron model by
      using the mean-field theory framework, synaptic depression has not been taken
      into consideration. We expanded the previous theoretical framework in this study
      to spiking neuron models with short-term synaptic depression. On the basis of
      this theory we analytically calculated neural correlations in a ring attractor
      network with Mexican-hat-type connectivity, which was used as a model of the
      primary visual cortex. The results revealed that synaptic depression reduces
      neural correlation, which could be beneficial for sensory coding. Furthermore,
      our study opens the way for theoretical studies on the effect of interaction
      change on the linear response function in large stochastic networks.

PMID- 22400627
TI  - Modularity-based graph partitioning using conditional expected models.
AB  - Modularity-based partitioning methods divide networks into modules by comparing
      their structure against random networks conditioned to have the same number of
      nodes, edges, and degree distribution. We propose a novel way to measure
      modularity and divide graphs, based on conditional probabilities of the edge
      strength of random networks. We provide closed-form solutions for the expected
      strength of an edge when it is conditioned on the degrees of the two neighboring
      nodes, or alternatively on the degrees of all nodes comprising the network. We
      analytically compute the expected network under the assumptions of Gaussian and
      Bernoulli distributions. When the Gaussian distribution assumption is violated,
      we prove that our expression is the best linear unbiased estimator. Finally, we
      investigate the performance of our conditional expected model in partitioning
      simulated and real-world networks.

PMID- 22400628
TI  - Least-effort trajectories lead to emergent crowd behaviors.
AB  - Pedestrian crowds often have been modeled as many-particle systems, usually using
      computer models known as multiagent simulations. The key challenge in modeling
      crowds is to develop rules that guide how the particles or agents interact with
      each other in a way that faithfully reproduces paths and behaviors commonly seen
      in real human crowds. Here, we propose a simple and intuitive formulation of
      these rules based on biomechanical measurements and the principle of least
      effort. We present a constrained optimization method to compute collision-free
      paths of minimum caloric energy for each agent, from which collective crowd
      behaviors can be reproduced. We show that our method reproduces common crowd
      phenomena, such as arching and self-organization into lanes. We also validate the
      flow rates and paths produced by our method and compare them to those of real
      world crowd trajectories.

PMID- 22400629
TI  - Improvement of pedestrian flow by slow rhythm.
AB  - We have developed a simple model for pedestrians by dividing walking velocity
      into two parts, which are step size and pace of walking (number of steps per unit
      time). Theoretical analysis on pace indicates that rhythm that is slower than
      normal-walking pace in a low-density regime increases flow if the flow-density
      diagram is convex downward in a high-density regime. In order to verify this
      result, we have performed an experiment with real pedestrians and observed the
      improvement of flow in a congested situation using slow rhythm.

PMID- 22400630
TI  - Percolation of partially interdependent networks under targeted attack.
AB  - We study a system composed of two partially interdependent networks; when nodes
      in one network fail, they cause dependent nodes in the other network to also
      fail. In this paper, the percolation of partially interdependent networks under
      targeted attack is analyzed. We apply a general technique that maps a targeted
      attack problem in interdependent networks to a random-attack problem in a
      transformed pair of interdependent networks. We illustrate our analytical
      solutions for two examples: (i) the probability for each node to fail is
      proportional to its degree, and (ii) each node has the same probability to fail
      in the initial time. We find the following: (i) For any targeted-attack problem,
      for the case of weak coupling, the system shows a second order phase transition,
      and for the strong coupling, the system shows a first order phase transition.
      (ii) For any coupling strength, when the high degree nodes have higher
      probability to fail, the system becomes more vulnerable. (iii) There exists a
      critical coupling strength, and when the coupling strength is greater than the
      critical coupling strength, the system shows a first order transition; otherwise,
      the system shows a second order transition.

PMID- 22400631
TI  - Consensus in networks of mobile communicating agents.
AB  - Populations of mobile and communicating agents describe a vast array of
      technological and natural systems, ranging from sensor networks to animal groups.
      Here, we investigate how a group-level agreement may emerge in the continuously
      evolving network defined by the local interactions of the moving individuals. We
      adopt a general scheme of motion in two dimensions and we let the individuals
      interact through the minimal naming game, a prototypical scheme to investigate
      social consensus. We distinguish different regimes of convergence determined by
      the emission range of the agents and by their mobility, and we identify the
      corresponding scaling behaviors of the consensus time. In the same way, we
      rationalize also the behavior of the maximum memory used during the convergence
      process, which determines the minimum cognitive/storage capacity needed by the
      individuals. Overall, we believe that the simple and general model presented in
      this paper can represent a helpful reference for a better understanding of the
      behavior of populations of mobile agents.

PMID- 22400632
TI  - Influence of the network topology on epidemic spreading.
AB  - The influence of the network's structure on the dynamics of spreading processes
      has been extensively studied in the last decade. Important results that partially
      answer this question show a weak connection between the macroscopic behavior of
      these processes and specific structural properties in the network, such as the
      largest eigenvalue of a topology related matrix. However, little is known about
      the direct influence of the network topology on the microscopic level, such as
      the influence of the (neighboring) network on the probability of a particular
      node's infection. To answer this question, we derive both an upper and a lower
      bound for the probability that a particular node is infective in a susceptible
      infective-susceptible model for two cases of spreading processes: reactive and
      contact processes. The bounds are derived by considering the n-hop neighborhood
      of the node; the bounds are tighter as one uses a larger n-hop neighborhood to
      calculate them. Consequently, using local information for different neighborhood
      sizes, we assess the extent to which the topology influences the spreading
      process, thus providing also a strong macroscopic connection between the former
      and the latter. Our findings are complemented by numerical results for a real
      world email network. A very good estimate for the infection density rho is
      obtained using only two-hop neighborhoods, which account for 0.4% of the entire
      network topology on average.

PMID- 22400633
TI  - Overlapping community detection via network dynamics.
AB  - The modular structure of a network is closely related to the dynamics toward
      clustering. In this paper, a method for community detection is proposed via the
      clustering dynamics of a network. The initial phases of the nodes in the network
      are given randomly, and then they evolve according to a set of dedicatedly
      designed differential equations. The phases of the nodes are naturally separated
      into several clusters after a period of evolution, and each cluster corresponds
      to a community in the network. For the networks with overlapping communities, the
      phases of the overlapping nodes will evolve to the interspace of the two
      communities. The proposed method is illustrated with applications to both
      synthetically generated and real-world complex networks.

PMID- 22400634
TI  - Competition of strength and stress disorder in creep rupture.
AB  - Based on a fiber bundle model of subcritical fracture with localized load
      sharing, we show that the interplay of threshold disorder and the inhomogeneous
      stress field gives rise to a rich dynamics with intriguing aspects. In the model,
      fibers fail either due to immediate breaking or to a slow damage process. When
      the disorder is strong, a large amount of damage occurs, which is randomly
      diffused over the system; however, for weak disorder, a single growing crack is
      formed, which proceeds in a large number of localized bursts. The microstructure
      of cracks is characterized by a power-law size distribution, which is analogous
      to percolation in the regime of diffusive damage; however, it becomes
      significantly steeper when a single crack dominates. Simulations showed that the
      size distribution of breaking bursts and of the waiting times in between have a
      power-law functional form with a load-dependent cutoff. The burst size exponent
      proved to be independent of the damage process; however, it strongly depends on
      the external load with a minimum value of 1.75. The waiting time distribution is
      sensitive to the details of the damage process with an exponent decreasing from
      2.0 to 1.4 as bursts get more and more localized to an advancing crack front.

PMID- 22400635
TI  - Overview of metrics and their correlation patterns for multiple-metric topology
      analysis on heterogeneous graph ensembles.
AB  - This study is an overview of network topology metrics and a computational
      approach to analyzing graph topology via multiple-metric analysis on graph
      ensembles. The paper cautions against studying single metrics or combining
      disparate graph ensembles from different domains to extract global patterns. This
      is because there often exists considerable diversity among graphs that share any
      given topology metric, patterns vary depending on the underlying graph
      construction model, and many real data sets are not actual statistical ensembles.
      As real data examples, we present five airline ensembles, comprising temporal
      snapshots of networks of similar topology. Wikipedia language networks are shown
      as an example of a nontemporal ensemble. General patterns in metric correlations,
      as well as exceptions, are discussed by representing the data sets via
      hierarchically clustered correlation heat maps. Most topology metrics are not
      independent and their correlation patterns vary across ensembles. In general,
      density-related metrics and graph distance-based metrics cluster and the two
      groups are orthogonal to each other. Metrics based on degree-degree correlations
      have the highest variance across ensembles and cluster the different data sets on
      par with principal component analysis. Namely, the degree correlation, the s
      metric, their elasticities, and the rich club moments appear to be most useful in
      distinguishing topologies.

PMID- 22400636
TI  - Solving the accuracy-diversity dilemma via directed random walks.
AB  - Random walks have been successfully used to measure user or object similarities
      in collaborative filtering (CF) recommender systems, which is of high accuracy
      but low diversity. A key challenge of a CF system is that the reliably accurate
      results are obtained with the help of peers' recommendation, but the most useful
      individual recommendations are hard to be found among diverse niche objects. In
      this paper we investigate the direction effect of the random walk on user
      similarity measurements and find that the user similarity, calculated by directed
      random walks, is reverse to the initial node's degree. Since the ratio of small
      degree users to large-degree users is very large in real data sets, the large
      degree users' selections are recommended extensively by traditional CF
      algorithms. By tuning the user similarity direction from neighbors to the target
      user, we introduce a new algorithm specifically to address the challenge of
      diversity of CF and show how it can be used to solve the accuracy-diversity
      dilemma. Without relying on any context-specific information, we are able to
      obtain accurate and diverse recommendations, which outperforms the state-of-the
      art CF methods. This work suggests that the random-walk direction is an important
      factor to improve the personalized recommendation performance.

PMID- 22400637
TI  - Adaptive synchronization in delay-coupled networks of Stuart-Landau oscillators.
AB  - We consider networks of delay-coupled Stuart-Landau oscillators. In these
      systems, the coupling phase has been found to be a crucial control parameter. By
      proper choice of this parameter one can switch between different synchronous
      oscillatory states of the network. Applying the speed-gradient method, we derive
      an adaptive algorithm for an automatic adjustment of the coupling phase such that
      a desired state can be selected from an otherwise multistable regime. We propose
      goal functions based on both the difference of the oscillators and a generalized
      order parameter and demonstrate that the speed-gradient method allows one to find
      appropriate coupling phases with which different states of synchronization, e.g.,
      in-phase oscillation, splay, or various cluster states, can be selected.

PMID- 22400638
TI  - Classical analog of quasilinear Landau-Zener tunneling.
AB  - In this paper we develop an analytical framework to study the effect of
      nonlinearity on irreversible energy transfer in a system of two weakly coupled
      oscillators with time-dependent parameters, with special attention to an analogy
      between classical energy transfer and nonadiabatic quantum tunneling. For
      preciseness, we suppose that a linear oscillator with constant parameters is
      excited by an initial impulse but a coupled quasilinear oscillator with slowly
      varying parameters is initially at rest. It is shown that the equations of the
      slow passage through resonance in this system are identical to quasilinear
      equations of nonadiabatic Landau-Zener tunneling. Due to revealed equivalence, a
      recently found analogy between irreversible energy transfer in a classical linear
      system and conventional linear Landau-Zener tunneling can be extended to
      quasilinear systems. An explicit analytical solution of the quasilinear problem
      is found with the help of an iteration procedure, wherein the linear solution is
      chosen as an initial approximation. Correctness of the constructed approximations
      is confirmed by numerical simulations. The results presented in this paper, in
      addition to providing an analytical framework for understanding the transient
      dynamics of coupled oscillators, suggest an approximate procedure for solving the
      quasilinear Landau-Zener equations with arbitrary initial conditions over a
      finite time interval.

PMID- 22400639
TI  - Patterns of synchronization in the hydrodynamic coupling of active colloids.
AB  - A system of active colloidal particles driven by harmonic potentials to oscillate
      about the vertices of a regular polygon, with hydrodynamic coupling between all
      particles, is described by a piecewise linear model which exhibits various
      patterns of synchronization. Analytical solutions are obtained for this class of
      dynamical systems. Depending only on the number of particles, the synchronization
      occurs into states in which nearest neighbors oscillate in in-phase, antiphase,
      or phase-locked (time-shifted) trajectories.

PMID- 22400640
TI  - Annular billiard dynamics in a circularly polarized strong laser field.
AB  - We analyze the dynamics of a valence electron of the buckminsterfullerene
      molecule (C60) subjected to a circularly polarized laser field by modeling it
      with the motion of a classical particle in an annular billiard. We show that the
      phase space of the billiard model gives rise to three distinct trajectories:
      "whispering gallery orbits," which hit only the outer billiard wall; "daisy
      orbits," which hit both billiard walls (while rotating solely clockwise or
      counterclockwise for all time); and orbits that only visit the downfield part of
      the billiard, as measured relative to the laser term. These trajectories, in
      general, maintain their distinct features, even as the intensity is increased
      from 10(10) to 10(14) Wcm-2. We attribute this robust separation of phase space
      to the existence of twistless tori.

PMID- 22400641
TI  - Chaotic escape from an open vase-shaped cavity. I. Numerical and experimental
      results.
AB  - We present part I in a two-part study of an open chaotic cavity shaped as a vase.
      The vase possesses an unstable periodic orbit in its neck. Trajectories passing
      through this orbit escape without return. For our analysis, we consider a family
      of trajectories launched from a point on the vase boundary. We imagine a vertical
      array of detectors past the unstable periodic orbit and, for each escaping
      trajectory, record the propagation time and the vertical detector position. We
      find that the escape time exhibits a complicated recursive structure. This
      recursive structure is explored in part I of our study. We present an
      approximation to the Helmholtz equation for waves escaping the vase. By choosing
      a set of detector points, we interpolate trajectories connecting the source to
      the different detector points. We use these interpolated classical trajectories
      to construct the solution to the wave equation at a detector point. Finally, we
      construct a plot of the detector position versus the escape time and compare this
      graph to the results of an experiment using classical ultrasound waves. We find
      that generally the classical trajectories organize the escaping ultrasound waves.

PMID- 22400642
TI  - Chaotic escape from an open vase-shaped cavity. II. Topological theory.
AB  - We present part II of a study of chaotic escape from an open two-dimensional vase
      shaped cavity. A surface of section reveals that the chaotic dynamics is
      controlled by a homoclinic tangle, the union of stable and unstable manifolds
      attached to a hyperbolic fixed point. Furthermore, the surface of section
      rectifies escape-time graphs into sequences of escape segments; each sequence is
      called an epistrophe. Some of the escape segments (and therefore some of the
      epistrophes) are forced by the topology of the dynamics of the homoclinic tangle.
      These topologically forced structures can be predicted using the method called
      homotopic lobe dynamics (HLD). HLD takes a finite length of the unstable manifold
      and a judiciously altered topology and returns a set of symbolic dynamical
      equations that encode the folding and stretching of the unstable manifold. We
      present three applications of this method to three different lengths of the
      unstable manifold. Using each set of dynamical equations, we compute minimal sets
      of escape segments associated with the unstable manifold, and minimal sets
      associated with a burst of trajectories emanating from a point on the vase's
      boundary. The topological theory predicts most of the early escape segments that
      are found in numerical computations.

PMID- 22400643
TI  - Convection in stable and unstable fronts.
AB  - Density gradients across a reaction front can lead to convective fluid motion.
      Stable fronts require a heavier fluid on top of a lighter one to generate
      convective fluid motion. On the other hand, unstable fronts can be stabilized
      with an opposing density gradient, where the lighter fluid is on top. In this
      case, we can have a stable flat front without convection or a steady convective
      front of a given wavelength near the onset of convection. The fronts are
      described with the Kuramoto-Sivashinsky equation coupled to hydrodynamics
      governed by Darcy's law. We obtain a dispersion relation between growth rates and
      perturbation wave numbers in the presence of a density discontinuity accross the
      front. We also analyze the effects of this density change in the transition to
      chaos.

PMID- 22400644
TI  - Hierarchical synchrony of phase oscillators in modular networks.
AB  - We study synchronization of sinusoidally coupled phase oscillators on networks
      with modular structure and a large number of oscillators in each community. Of
      particular interest is the hierarchy of local and global synchrony, i.e.,
      synchrony within and between communities, respectively. Using the recent ansatz
      of Ott and Antonsen [Chaos 18, 037113 (2008)], we find that the degree of local
      synchrony can be determined from a set of coupled low-dimensional equations. If
      the number of communities in the network is large, a low-dimensional description
      of global synchrony can be also found. Using these results, we study bifurcations
      between different types of synchrony. We find that, depending on the relative
      strength of local and global coupling, the transition to synchrony in the network
      can be mediated by local or global effects.

PMID- 22400645
TI  - Diffusive transport of waves in a periodic waveguide.
AB  - We study the propagation of waves in quasi-one-dimensional finite periodic
      systems whose classical (ray) dynamics is diffusive. By considering a random
      matrix model for a chain of L identical chaotic cavities, we show that its
      average conductance as a function of L displays an ohmic behavior even though the
      system has no disorder. This behavior, with an average conductance decay N/L,
      where N is the number of propagating modes in the leads that connect the
      cavities, holds for 1?L??N. After this regime, the average conductance saturates
      at a value of O(?N) given by the average number of propagating Bloch modes <NB>
      of the infinite chain. We also study the weak localization correction and
      conductance distribution, and characterize its behavior as the system undergoes
      the transition from diffusive to Bloch ballistic. These predictions are tested in
      a periodic cosine waveguide.

PMID- 22400646
TI  - Coupling of bouncing-ball modes to the chaotic sea and their counting function.
AB  - We study the coupling of bouncing-ball modes to chaotic modes in two-dimensional
      billiards with two parallel boundary segments. Analytically, we predict the
      corresponding decay rates using the fictitious integrable system approach.
      Agreement with numerically determined rates is found for the stadium and the
      cosine billiard. We use this result to predict the asymptotic behavior of the
      counting function N_{bb}(E)~E^{delta}. For the stadium billiard we find agreement
      with the previous result delta=3/4. For the cosine billiard we derive delta=5/8,
      which is confirmed numerically and is well below the previously predicted upper
      bound delta=9/10.

PMID- 22400647
TI  - Estimation of entropy rate in a fast physical random-bit generator using a
      chaotic semiconductor laser with intrinsic noise.
AB  - We analyze the time for growth of bit entropy when generating nondeterministic
      bits using a chaotic semiconductor laser model. The mechanism for generating
      nondeterministic bits is modeled as a 1-bit sampling of the intensity of light
      output. Microscopic noise results in an ensemble of trajectories whose bit
      entropy increases with time. The time for the growth of bit entropy, called the
      memory time, depends on both noise strength and laser dynamics. It is shown that
      the average memory time decreases logarithmically with increase in noise
      strength. It is argued that the ratio of change in average memory time with
      change in logarithm of noise strength can be used to estimate the intrinsic
      dynamical entropy rate for this method of random bit generation. It is also shown
      that in this model the entropy rate corresponds to the maximum Lyapunov exponent.

PMID- 22400648
TI  - Deterministic Smoluchowski-Feynman ratchets driven by chaotic noise.
AB  - We have elucidated the effect of statistical asymmetry on the directed current in
      Smoluchowski-Feynman ratchets driven by chaotic noise. Based on the inhomogeneous
      Smoluchowski equation and its generalized version, we arrive at analytical
      expressions of the directed current that includes a source term. The source term
      indicates that statistical asymmetry can drive the system further away from
      thermodynamic equilibrium, as exemplified by the constant flashing, the state
      dependent, and the tilted deterministic Smoluchowski-Feynman ratchets, with the
      consequence of an enhancement in the directed current.

PMID- 22400649
TI  - Inwardly rotating spirals in nonuniform excitable media.
AB  - Inwardly rotating spirals (IRSs) have attracted great attention since their
      observation in an oscillatory reaction-diffusion system. However, IRSs have not
      yet been reported in planar excitable media. In the present work we investigate
      rotating waves in a nonuniform excitable medium, consisting of an inner disk part
      surrounded by an outer ring part with different excitabilities, by numerical
      simulations of a simple FitzHugh-Nagumo model. Depending on the excitability of
      the medium as well as the inhomogeneity, we find the occurrence of IRSs, of which
      the excitation propagates inwardly to the geometrical spiral tip.

PMID- 22400650
TI  - Poincare recurrences of DNA sequences.
AB  - We analyze the statistical properties of Poincare recurrences of Homo sapiens,
      mammalian, and other DNA sequences taken from the Ensembl Genome data base with
      up to 15 billion base pairs. We show that the probability of Poincare recurrences
      decays in an algebraic way with the Poincare exponent beta~4 even if the
      oscillatory dependence is well pronounced. The correlations between recurrences
      decay with an exponent nu~0.6 that leads to an anomalous superdiffusive walk.
      However, for Homo sapiens sequences, with the largest available statistics, the
      diffusion coefficient converges to a finite value on distances larger than one
      million base pairs. We argue that the approach based on Poncare recurrences
      determines new proximity features between different species and sheds a new light
      on their evolution history.

PMID- 22400651
TI  - Quasiperiodic, periodic, and slowing-down states of coupled heteroclinic cycles.
AB  - We investigate two coupled oscillators, each of which shows an attracting
      heteroclinic cycle in the absence of coupling. The two heteroclinic cycles are
      nonidentical. Weak coupling can lead to the elimination of the slowing-down state
      that asymptotically approaches the heteroclinic cycle for a single cycle, giving
      rise to either quasiperiodic motion with separate frequencies from the two cycles
      or periodic motion in which the two cycles are synchronized. The synchronization
      transition, which occurs via a Hopf bifurcation, is not induced by the
      commensurability of the two cycle frequencies but rather by the disappearance of
      the weaker frequency oscillation. For even larger coupling the motion changes via
      a resonant heteroclinic bifurcation to a slowing-down state corresponding to a
      single attracting heteroclinic orbit. Coexistence of multiple attractors can be
      found for some parameter regions. These results are of interest in ecological,
      sociological, neuronal, and other dynamical systems, which have the structure of
      coupled heteroclinic cycles.

PMID- 22400652
TI  - Effect of shock-generated turbulence on the Hugoniot jump conditions.
AB  - Interaction of a shock wave with preshock random density nonuniformities is known
      to generate turbulence in the postshock flow. The turbulent motion, in turn,
      modifies the shock jump conditions. As first detected in the simulations by Hazak
      et al. [Phys. Plasmas 5, 4357 (1998)], shock compression of a deuterium-filled
      foam is less than that predicted for a uniform medium of the same average
      density. Exact analytical small-amplitude theory of this shock undercompression
      effect is reported, and explicit formulas for the turbulent corrections to the
      strong-shock Hugoniot jump conditions are presented.

PMID- 22400653
TI  - Quasiadiabatic approach for laser-induced single-bubble sonoluminescence.
AB  - The luminescence parameters of laser-induced bubble in the presence of an
      acoustic field in water are studied. A comparison is made between parameters such
      as bubble radius, interior temperature, and pressure of the bubble induced by
      laser and an acoustic field influenced by different driving pressure amplitudes.
      It is found that the bubble volume induced by laser at the collapse instant is
      more than 10(6) times larger than the one induced by an acoustic field. It is
      also noticed, by increasing the driving pressure amplitude, the bubble radius
      decreases in both cases, however, the bubble interior pressure and temperature
      increase.

PMID- 22400654
TI  - Turbulent viscosity and turbulent magnetic diffusivity in a decaying spin-down
      flow of liquid sodium.
AB  - The free decay of a strong flow of liquid sodium (at Reynolds number defined via
      the maximal mean velocity and the radius of the channel cross section up to
      Re~3*10(60) and the corresponding magnetic Reynolds number up to Rm~30) generated
      by the sudden stop of a rapidly rotating toroidal channel is studied
      experimentally. The toroidal and poloidal components of velocity are measured
      using a potential probe. We describe the onset of motion, the evolution of
      strongly anisotropic fluctuations, and the homogenization and decay of turbulence
      in the final period. We analyze the statistical characteristics of velocity
      fields in relation to the behavior of effective magnetic diffusivity estimated
      from measurements of the phase shift between the induced and applied magnetic
      fields. For the late (self-similar) decay of turbulent flow, turbulent viscosity
      is shown to be dependent on the root-mean-square velocity pulsations and can be
      expressed as nut~nuRe1.3. The behavior of turbulent magnetic diffusivity depends
      on the magnetic Reynolds number defined in terms of the root-mean-square velocity
      pulsations. At low magnetic Reynolds numbers (Rmrms<1), turbulent magnetic
      diffusivity grows rapidly with increasing velocity pulsations (etat~etaRmrms2).
      If the magnetic Reynolds number exceeds unity, the behavior of turbulent magnetic
      diffusivity becomes similar to the behavior of turbulent viscosity. The highest
      values of turbulent magnetic diffusivity are achieved at the end of braking,
      which corresponds to the transient stage of a strongly anisotropic turbulent flow
      in which the poloidal velocity oscillations prevail.

PMID- 22400655
TI  - Generalized nonequilibrium capillary relations for two-phase flow through
      heterogeneous media.
AB  - For two-phase flow in porous media, the natural medium heterogeneity necessarily
      gives rise to capillary nonequilibrium effects. The relaxation to the equilibrium
      is a slow process which should be introduced in macroscopic flow models. Many
      nonequilibrium models are based on a phenomenological approach. At the same time
      there exists a rigorous mathematical way to develop the nonequilibrium equations.
      Its formalism, developed by Bourgeat and Panfilov [Computational Geosciences 2,
      191 (1998)], is based on the homogenization of the microscale flow equations over
      medium heterogeneities. In contrast with the mentioned paper, in which the case
      of a sufficiently fast relaxation was analyzed, we consider the case of long
      relaxation, which leads to the appearance of long-term memory on the macroscale.
      Due to coupling between the nonlinearity and nonlocality in time, the macroscopic
      model remains, however, incompletely homogenized, in the general case. At the
      same time, frequently only the relationship for the nonequilibrium capillary
      pressure is of interest for applications. In the present paper, we obtain such an
      exact relationship in two different independent forms for the case of long-term
      memory. This relationship is more general than that obtained by Bourgeat and
      Panfilov. In addition, we prove the comparison theorem which determines the upper
      and lower bounds for the macroscopic model. These bounds represent linear flow
      models, which are completely homogenized. The results obtained are illustrated by
      numerical simulations.

PMID- 22400656
TI  - Nonlinear bubble dynamics of cavitation.
AB  - For cavitation clouds generated in a standing sound wave driven by an ultrasonic
      horn, the nonlinear acoustic wave equation governing cavitation dynamics is
      numerically solved together with the bubble motion equation under an
      approximation. This conceptual calculation can qualitatively reproduce the
      observed characteristics of cavitation.

PMID- 22400657
TI  - Instability of a charged non-Newtonian liquid jet.
AB  - A three-dimensional instability analysis of an electrified non-Newtonian liquid
      jet is performed in this paper so as to understand the competition between
      viscoelastic stresses, electric force, and surface tension. The analysis employs
      the leaky-dielectric model to account for the charge transport process and the
      Oldroyd-B model to take the viscoelastic effect into account. Results show that
      the viscoelastic stresses play a stabilizing role while electrification
      destabilizes the disturbances with shorter wavelength and higher azimuthal wave
      numbers. However, the viscoelastic stabilizing effect is not so significant on
      the sinuous mode (with azimuthal wave number m = 1) compared with the other
      modes, which thus promotes sinuous disturbances. This result is consistent with
      the presence of bending motion in most experimental observations.

PMID- 22400658
TI  - Deformation of a single red blood cell in bounded Poiseuille flows.
AB  - Deformation of a red blood cell (RBC) in bounded two-dimensional Poiseuille flows
      is studied by using an immersed boundary method (IBM). An elastic spring model is
      applied to simulate the skeleton structure of a RBC membrane. As a benchmarking
      test, the dynamical behavior of a single RBC under a simple shear flow has been
      validated. Then we focus on investigating the motion and the deformation of a
      single RBC in Poiseuille flows by varying the swelling ratio (s*), the initial
      angle of the long axis of the cell at the centerline (phi), the maximum velocity
      at the centerline of fluid flow (umax), the membrane bending stiffness of a RBC
      (kb), and the height of the microchannel (H). Two motions of oscillation and
      vacillating breathing (swing) of a RBC are observed in both narrow and wide
      channels. The strength of the vacillating-breathing motion depends on the degree
      of confinement and the value of umax. A RBC exhibits a strong vacillating
      breathing motion as the degree of confinement is larger or the value of umax is
      higher. For the same degree of confinement, the vacillating-breathing motion
      appears to be relatively weaker but persists longer as the value of umax is
      lower. The continuation of shape change from the slippery to the parachute by
      varying the value of umax is obtained for the biconcave shape cell in a narrower
      channel. In particular, parachute shape and bulletlike shape, depending on the
      angle phi, coexist for the elliptic shape cell given initially with lower umax in
      a narrower channel.

PMID- 22400659
TI  - Two-fluid confined flow in a cylinder driven by a rotating end wall.
AB  - The flow of two immiscible fluids completely filling an enclosed cylinder and
      driven by the rotation of the bottom end wall is studied numerically. The
      simulations are in parameter regimes where there is significant advection of
      angular momentum, i.e., the disk rotation rate is fast compared to the viscous
      diffusion time. We consider two classes of scenarios. The first consists of cases
      that are straightforward to reproduce in physical experiments where only the
      rotation rate and the viscosity ratio of the fluids are varied. Then we isolate
      different forces acting on the system such as inertia, surface tension, and
      gravity by studying variations in individual governing parameters. The viscosity
      ratio determines how quickly the upper fluid equilibriates dynamically to the
      flow in the lower fluid and plays a major role in determining how vortex lines
      are bent in the neighborhood of the interface between the two fluids. This in
      turn determines the structure of the interfacial layer between the two swirling
      fluids, which is responsible for the flow in the upper fluid. The simulations
      show that even when there is significant interfacial deformation, both the
      dynamics and the equilibrium flow are dominated by vortex bending rather than
      vortex stretching. The simulations show that for the range of immiscible fluids
      considered, surface tension effects are significant. Increased surface tension
      reduces the degree to which the interface is deformed and the limit of zero
      surface tension is not an appropriate approximation.

PMID- 22400660
TI  - Segregation in water-based stable single-bubble sonoluminescence.
AB  - A long-standing issue in the field of long-time-stable, water-based, single
      bubble sonoluminescence has been the close similarity of the spectra to that of
      blackbody radiation, the question being whether the similarity is just a weird
      coincidence, with the bubbles being, on the whole, transparent to their own
      radiation. One mechanism that has been suggested is the generation of a shock or,
      at least, a compression wave in the gas of the bubble. A footprint of such a wave
      would be segregation of species. We have investigated spectra from bubbles seeded
      with various mixtures of helium or neon with xenon or argon using a
      transformation, specific to our experimental setup and spectrometer, that was
      shown to allow for a single-parameter characterization of the spectra in some
      simpler situations. The surprising result of this investigation is that although
      no trace of segregation is found, the radiation seems to be highly thermalized in
      all cases.

PMID- 22400661
TI  - Scalings of field correlations and heat transport in turbulent convection.
AB  - Using direct numerical simulations of Rayleigh-Benard convection under free-slip
      boundary condition, we show that the normalized correlation function between the
      vertical velocity field and the temperature field, as well as the normalized
      viscous dissipation rate, scales as Ra-0.22 for moderately large Rayleigh number
      Ra. This scaling accounts for the Nusselt number Nu exponent of approximately
      0.3, as observed in experiments. Numerical simulations also reveal that the
      aforementioned normalized correlation functions are constants for the convection
      simulation under periodic boundary conditions.

PMID- 22400662
TI  - Dynamics of inertial particles in a random flow with strong permanent shear.
AB  - We consider advection of small inertial particles by a random fluid flow with a
      strong steady shear component. It is known that inertial particles suspended in a
      random flow can exhibit clusterization even if the flow is incompressible. We
      study this phenomenon through statistical characteristics of a separation vector
      between two particles. As usual in a random flow, moments of distance between
      particles grow exponentially. We calculate the rates of this growth using saddle
      point approximation in path-integral formalism. We also calculate the correction
      to the Lyapunov exponent due to small inertia by perturbation theory expansion.

PMID- 22400663
TI  - Effect of fluid inertia on probe-tack adhesion.
AB  - One way of determining the adhesive strength of liquids is provided by a probe
      tack test, which involves measuring the force required to pull apart two parallel
      flat plates separated by a thin fluid film. The large majority of existing
      theoretical and experimental work on probe-tack adhesion use very viscous fluids
      and considers relatively low lifting plate velocities, so that effects due to
      fluid inertia can be neglected. However, the employment of low-viscosity fluids
      and the increase in operating speeds of modern lifting apparatus can modify this
      scenario. By dealing with a proper gap averaging of the Navier-Stokes equation,
      we obtain a modified Darcy-law-like description of the problem and derive an
      adhesion force which incorporates the effects of fluid inertia, fluid viscosity
      (for Newtonian and power law fluids), and the contribution of the compliance and
      inertia of the probe-tack apparatus. Our results indicate that fluid inertia may
      have a significant influence on the adhesion force profiles, inducing a
      considerable increase in the force peaks and producing oscillations in the force
      displacement curves as the plate-plate separation is increased. The combined role
      of inertial and non-Newtonian fluid behaviors on the adhesion force response is
      also investigated.

PMID- 22400664
TI  - Thermal evidence for Taylor columns in turbulent rotating Rayleigh-Benard
      convection.
AB  - We investigate flow structures in rotating Rayleigh-Benard convection experiments
      in water using thermal measurements. We focus on correlations between time series
      measurements of temperature in the top and bottom boundaries. Distinct
      anticorrelations are observed for rapidly rotating convection, which are argued
      to attest to heat transport by convective Taylor columns. In support of this
      argument, these quasigeostrophic flow structures are directly observed in flow
      visualizations, and their thermal signature is qualitatively reproduced by a
      simple model of heat transport by columnar flow. Weakly rotating and nonrotating
      convection produces positively correlated temperature changes across the layer,
      indicative of heat transport by large-scale circulation. We separate these
      regimes using a transition parameter that depends on the Rayleigh and Ekman
      numbers, RaE3/2.

PMID- 22400665
TI  - Spreading profile of evaporative liquid drops in thin porous layer.
AB  - Spreading of evaporative liquid drops in a thin porous layer has been studied.
      The entire spreading process can be divided into three distinct phases according
      to the change of the wetted porous region size. The first phase is characterized
      by the expansion of the wetted porous region and shrinking of the liquid drop.
      Contact line pinning is observed in the wetted porous region in the second phase
      even with the liquid drop totally absorbed into the porous layer. The third phase
      sees the shrinkage of the wetted porous region until it is not observable. Based
      on these observations, a model is devised to simulate the spreading of a liquid
      drop under the studied conditions. Partial differential equations are used to
      describe the relation between liquid drop volume and other important parameters
      of a fluid flow, including maximum wetted region diameter achieved, time taken to
      reach each spreading process phase, and evaporation rate. Calculated results are
      in good agreement with the experimental data.

PMID- 22400666
TI  - Surface-charge-induced alteration of nanovortex patterning in nanoscale
      confinements with patterned wettability gradients.
AB  - We characterize the generation of flow vortices in nanoscale confinements under
      the combined effects of patterned surface charge density and substrate
      wettability. Using molecular dynamics simulations, we elucidate the effects of
      ion solvation and steric interactions toward influencing the resultant transport
      characteristics, which are otherwise difficult to resolve using classical
      electrokinetic theory. We also evaluate the velocity slip (local and global) as
      well as vorticity parameters, in an effort to assess the implications of the
      generated flow structure from a pseudocontinuum viewpoint. Results from the
      present study are expected to provide valuable insights on augmentation of
      nanoscale mixing.

PMID- 22400667
TI  - Dispersion in porous media, continuous-time random walks, and percolation.
AB  - A promising approach to the modeling of anomalous (non-Gaussian) dispersion in
      flow through heterogeneous porous media is the continuous-time random walk (CTRW)
      method. In such a formula on the waiting time distribution psi(t) is usually
      assumed to be given by psi(t)~t-1-alpha, with alpha fitted to the experimental
      data. The exponent alpha is also related to the power-law growth of the mean
      square displacement of the solute with the time t <R2(t)> ~ tzeta. Invoking
      percolation and using a scaling analysis, we relate alpha to the geometrical
      exponents of percolation (nu, beta, and betaB) as well as the exponents MU and e
      that characterize the power-law behavior of the effective conductivity and
      permeability of porous media near the percolation threshold. We then explain the
      cause of the nonuniversality of alpha in terms of the nonuniversality of MU and e
      in continuum systems, and in percolation models with long-range correlations, and
      propose bounds for it. The results are consistent with the experimental data,
      both at the laboratory and field scales.

PMID- 22400668
TI  - Pore-scale evaporation-condensation dynamics resolved by synchrotron x-ray
      tomography.
AB  - Capillary processes greatly influence vapor mediated transport dynamics and
      associated changes in liquid phase content of porous media. Rapid x-ray
      synchrotron tomography measurements were used to resolve liquid-vapor interfacial
      dynamics during evaporation and condensation within submillimetric pores forming
      between sintered glass bead samples subjected to controlled ambient temperature
      and relative humidity. Evolution of gas-liquid interfacial shapes were in
      agreement with predictions based on our analytical model for interfacial dynamics
      in confined wedge-shaped pores. We also compared literature experimental data at
      the nanoscale to illustrate the capability of our model to describe early stages
      of condensation giving rise to the onset of capillary forces between rough
      surfaces. The study provides high resolution, synchrotron-based observations of
      capillary evaporation-condensation dynamics at the pore scale as the confirmation
      of the pore scale analytical model for capillary condensation in a pore and
      enables direct links with evolution of macroscopic vapor gradients within a
      sintered glass bead sample through their effect on configuration and evolution of
      the local interfaces. Rapid condensation processes play a critical role in the
      onset of capillary-induced friction affecting mechanical behavior of physical
      systems and industrial applications.

PMID- 22400669
TI  - Dynamics of primary and secondary microbubbles created by laser-induced breakdown
      of an optically trapped nanoparticle.
AB  - Laser-induced breakdown of an optically trapped nanoparticle is a unique system
      for studying cavitation dynamics. It offers additional degrees of freedom, namely
      the nanoparticle material, its size, and the relative position between the laser
      focus and the center of the optically trapped nanoparticle. We quantify the
      spatial and temporal dynamics of the cavitation and secondary bubbles created in
      this system and use hydrodynamic modeling to quantify the observed dynamic shear
      stress of the expanding bubble. In the final stage of bubble collapse, we
      visualize the formation of multiple submicrometer secondary bubbles around the
      toroidal bubble on the substrate. We show that the pattern of the secondary
      bubbles typically has its circular symmetry broken along an axis whose unique
      angle rotates over time. This is a result of vorticity along the jet towards the
      boundary upon bubble collapse near solid boundaries.

PMID- 22400670
TI  - Coupling electrokinetics and rheology: Electrophoresis in non-Newtonian fluids.
AB  - We present a theoretical scheme to calculate the electrophoretic motion of
      charged colloidal particles immersed in complex (non-Newtonian) fluids possessing
      shear-rate-dependent viscosities. We demonstrate that this non-Newtonian rheology
      leads to an explicit shape and size dependence of the electrophoretic velocity of
      a uniformly charged particle in the thin-Debye-layer regime, in contrast to
      electrophoresis in Newtonian fluids. This dependence is caused by non-Newtonian
      stresses in the bulk (electroneutral) fluid outside the Debye layer, whose
      magnitude is naturally characterized in an electrophoretic Deborah number.

PMID- 22400671
TI  - Electromagnetic propulsion and separation by chirality of nanoparticles in
      liquids.
AB  - We introduce a new mechanism for the propulsion and separation by chirality of
      small ferromagnetic particles suspended in a liquid. Under the action of a
      uniform dc magnetic field H and an ac electric field E isomers with opposite
      chirality move in opposite directions. Such a mechanism could have a significant
      impact on a wide range of emerging technologies. The component of the chiral
      velocity that is odd in H is found to be proportional to the intrinsic orbital
      and spin angular momentum of the magnetized electrons. This effect arises because
      a ferromagnetic particle responds to the applied torque as a small gyroscope.

PMID- 22400672
TI  - Droplet formation in microfluidic T-junction generators operating in the
      transitional regime. I. Experimental observations.
AB  - This is the first part of a two-part study on the generation of droplets at a
      microfluidic T-junction operating in the transition regime where confinement of
      the droplet creates a large squeezing pressure that influences droplet formation.
      In this regime, the operation of the T-junction depends on the geometry of the
      intersection (height-to-width ratio, inlet width ratio), capillary number, flow
      ratio, and viscosity ratio of the two phases. Here in paper I we presented our
      experimental observations through the analysis of high-speed videos of the
      droplet formation process. Various parameters are tracked during the formation
      cycle such as the shape of the droplet (penetration depth and neck), interdroplet
      spacing, production rate, and flow of both phases across several T-junction
      designs and flow conditions. Generally, the formation process is defined by a two
      stage model consisting of an initial filling stage followed by a necking stage.
      However, video evidence suggests the inclusion of a third stage, which we term
      the lag stage, at the beginning of the formation process that accounts for the
      retraction of the interface back into the injection channel after detachment.
      Based on the observations made in this paper, a model is developed to describe
      the formation process in paper II, which can be used to understand the design and
      operation of T-junction generators in the transition regime.

PMID- 22400673
TI  - Droplet formation in microfluidic T-junction generators operating in the
      transitional regime. II. Modeling.
AB  - This is the second part of a two-part study on the generation of droplets at a
      microfluidic T-junction operating in the transition regime. In the preceding
      paper [Phys. Rev. E 85, 016322 (2012)], we presented our experimental
      observations of droplet formation and decomposed the process into three
      sequential stages defined as the lag, filling, and necking stages. Here we
      develop a model that describes the performance of microfluidic T-junction
      generators working in the squeezing to transition regimes where confinement of
      the droplet dominates the formation process. The model incorporates a detailed
      geometric description of the drop shape during the formation process combined
      with a force balance and necking criteria to define the droplet size, production
      rate, and spacing. The model inherently captures the influence of the
      intersection geometry, including the channel width ratio and height-to-width
      ratio, capillary number, and flow ratio, on the performance of the generator. The
      model is validated by comparing it to speed videos of the formation process for
      several T-junction geometries across a range of capillary numbers and viscosity
      ratios.

PMID- 22400674
TI  - Tensorial slip of superhydrophobic channels.
AB  - We describe a generalization of the tensorial slip boundary condition, originally
      justified for a thick (compared to texture period) channel, to any channel
      thickness. The eigenvalues of the effective slip-length tensor, however, in
      general case become dependent on the gap and cannot be viewed as a local property
      of the surface, being a global characteristic of the channel. To illustrate the
      use of the tensor formalism we develop a semianalytical theory of an effective
      slip in a parallel-plate channel with one superhydrophobic striped and one
      hydrophilic surface. Our approach is valid for any local slip at the gas sectors
      and an arbitrary distance between the plates, ranging from a thick to a thin
      channel. We then present results of lattice Boltzmann simulations to validate the
      analysis. Our results may be useful for extracting effective slip tensors from
      global measurements, such as the permeability of a channel, in experiments or
      simulations.

PMID- 22400675
TI  - Scattering and nonlinear bound states of hydrodynamically coupled particles in a
      narrow channel.
AB  - We model a pair of hydrodynamically interacting particles confined in a channel
      with thin rectangular cross section. We find that the particles have a finite
      region of attraction, which arises from the screening of dipolar hydrodynamic
      interactions by the side walls. Outside this region, the two particles break
      apart and scatter; inside, they oscillate together as an effectively free
      quasiparticle. We demonstrate that modulation of channel geometry provides a
      means to irreversibly manipulate bound pairs.

PMID- 22400676
TI  - Mixing generated by Faraday instability between miscible liquids.
AB  - The mixing between two miscible liquids subject to vertical vibrations is studied
      by way of experiments and a two-dimensional numerical model. The experimental
      setup consisted of a rectangular cell in which the lighter fluid was placed above
      the denser one. The diffuse interface was then visualized by a high-speed camera.
      After an initial period of diffusion growth, the interface becomes unstable with
      a defined wavelength, which depends on the amplitude and frequency of the
      acceleration. The waviness of the interfacial region disappears once the mixing
      of the two fluids takes place. The mixing is characterized by a mixing layer
      thickness (MLT) which measures the thickness of the mixed region between the two
      pure fluid domains. We find that the MLT shows an exponential growth with time
      due to an initial fingering that appears at the interface and then a growth with
      a defined slope after the mixing takes place. The MLT also increases with
      amplitude of driving motion. Experimentally determined MLTs are always greater
      than those determined by computations since the latter assume a jump
      discontinuity between the fluids prior to shaking, whereas in an experiment an
      initial diffusive region establishes itself prior to shaking and this is
      destabilizing. In addition, it is found from computations that mixing is best for
      low gravity levels at earlier times and high gravity levels at longer times.
      Explanations are advanced for each of these observations.

PMID- 22400677
TI  - Forces acting on a small particle in an acoustical field in a viscous fluid.
AB  - We calculate the acoustic radiation force from an ultrasound wave on a
      compressible, spherical particle suspended in a viscous fluid. Using Prandtl
      Schlichting boundary-layer theory, we include the kinematic viscosity of the
      solvent and derive an analytical expression for the resulting radiation force,
      which is valid for any particle radius and boundary-layer thickness provided that
      both of these length scales are much smaller than the wavelength of the
      ultrasound wave (millimeters in water at megahertz frequencies). The
      acoustophoretic response of suspended microparticles is predicted and analyzed
      using parameter values typically employed in microchannel acoustophoresis.

PMID- 22400678
TI  - Long-wave Marangoni convection in a thin film heated from below.
AB  - We consider long-wave Marangoni convection in a liquid layer atop a substrate of
      low thermal conductivity, heated from below. We demonstrate that the critical
      perturbations are materialized at the wave number K ~ ?Bi, where Bi is the Biot
      number which characterizes the weak heat flux from the free surface. In addition
      to the conventional monotonic mode, a novel oscillatory mode is found. Applying
      the K ~ ?Bi scaling, we derive a new set of amplitude equations. Pattern
      selection on square and hexagonal lattices shows that supercritical branching is
      possible. A large variety of stable patterns is found for both modes of
      instability. Finite-amplitude one-dimensional solutions of the set, corresponding
      to either steady or traveling rolls, are studied numerically; a complicated
      sequence of bifurcations is found in the former case. The emergence of an
      oscillatory mode in the case of heating from below and stable patterns with
      finite-amplitude surface deformation are shown in this system for the first time.

PMID- 22400679
TI  - Ambient temperature effect on single-bubble sonoluminescence in different
      concentrations of sulfuric acid solutions.
AB  - The effect of ambient temperature on the parameters of the single-bubble
      sonoluminescence in sulfuric acid (SA) diluted in water is studied. Using a
      hydrochemical model, three dominant instabilities of shape, Bjerknes, and
      diffusion are considered. The phase diagrams of the bubble in the (R0 - Pa) space
      are presented, and the parametric dependence of the light intensity is discussed.
      In contrast to water, the calculated thermal-bremsstrahlung mechanism of light
      emission at the fixed degassing condition of high SA concentrations shows that,
      with increasing the temperature of aqueous SA solutions, the light intensity
      increases. However, at diluted SA solutions similar to water, the light intensity
      decreases with increasing the ambient temperature. For 50 wt % SA, it was
      observed that the emitted light was almost temperature independent. Furthermore,
      it is found that, at the fixed temperatures of 20  degrees C, 10  degrees C, and
      0  degrees C, the aqueous solutions of 65 wt %, 50 wt %, and 45 wt % SA,
      respectively, have the maximum light emission.

PMID- 22400680
TI  - Fluid flow beneath a semipermeable membrane during drying processes.
AB  - The dynamic interactions between a semipermeable membrane and a long, thin layer
      of liquid beneath it are investigated in the context of drying processes. The
      membrane separates two aqueous solutions of sugar, and the transport of water
      across the membrane is driven by concentration and pressure gradients across it.
      A model is formulated using a long-wave approximation that includes the effects
      of volume loss due to water transport across the membrane, the incompressibility
      and bending stiffness of the membrane, and the dynamical effects that arise owing
      to the viscous stresses generated by the fluid flow. This model is first applied
      to study the desiccation of a sessile vesicle that is clamped to a rigid
      substrate and then also to study the behavior of blisters on laminated
      substrates. For each problem, equilibrium membrane shapes are obtained and their
      bifurcation structures are described as the sugar concentration above the
      membrane is varied. It is demonstrated that a wrinkled membrane coarsens to
      lessen the frequency of wrinkles and that if the membrane is clamped
      symmetrically so that it meets the substrate at a nonzero angle, then the
      membrane favors an asymmetric shape as water is drawn out through it.

PMID- 22400681
TI  - Covariant Lyapunov analysis of chaotic Kolmogorov flows.
AB  - Hyperbolicity is an important concept in dynamical system theory; however, we
      know little about the hyperbolicity of concrete physical systems including fluid
      motions governed by the Navier-Stokes equations. Here, we study numerically the
      hyperbolicity of the Navier-Stokes equation on a two-dimensional torus
      (Kolmogorov flows) using the method of covariant Lyapunov vectors developed by
      Ginelli et al. [Phys. Rev. Lett. 99, 130601 (2007)]. We calculate the angle
      between the local stable and unstable manifolds along an orbit of chaotic
      solution to evaluate the hyperbolicity. We find that the attractor of chaotic
      Kolmogorov flows is hyperbolic at small Reynolds numbers, but that smaller angles
      between the local stable and unstable manifolds are observed at larger Reynolds
      numbers, and the attractor appears to be nonhyperbolic at a certain Reynolds
      numbers. Also, we observed some relations between these hyperbolic properties and
      physical properties such as time correlation of the vorticity and the energy
      dissipation rate.

PMID- 22400682
TI  - Terahertz radiation generation by beating of two spatial-Gaussian lasers in the
      presence of a static magnetic field.
AB  - Resonant excitation of terahertz (THz) radiation based on beating of two spatial
      Gaussian lasers having different frequencies and wave numbers but the same
      electric field amplitudes is proposed in a spatially periodic density plasma in
      the presence of a static magnetic field applied perpendicular to the direction of
      propagation of the lasers. In this process, the ponderomotive force is developed
      with its components parallel and perpendicular to the direction of propagation of
      the lasers. This leads to a nonlinear oscillatory current that resonantly excites
      the THz radiation with the frequency of the order of the upper hybrid frequency.
      The contribution of magnetic field, laser beamwidth, and amplitude and
      periodicity of the density ripples is discussed for the efficient THz radiation
      generation. With the optimization of these parameters, the efficiency on the
      order of 10(-3) or larger can be achieved in the present scheme.

PMID- 22400683
TI  - Time evolution and energy deposition for ion clusters injected into magnetized
      two-component plasmas.
AB  - A two-dimensional particle-in-cell simulation model is proposed to study the time
      evolution and energy deposition for ion clusters injected into magnetized two
      component plasmas. The injection of an isolated ion cluster is studied in the
      case of weak and strong magnetic fields. For strong magnetic fields, the ions
      tend to deposit their energy smoothly along the trajectory of the cluster, due to
      the confinement by the strong magnetic fields. However, in the case of weak
      magnetic fields, a large amount of energy is deposited by the ions near the
      initial cluster injection position, where the cluster density is expected to be
      largest. We attribute these to the influences of interference effects between the
      cluster ions, which have close relations to the distances between the ions.
      Furthermore, the influences of various magnetic fields, injection angles, and
      injection velocities on the time evolution and energy deposition of a beam pulse,
      which contains several similar ion clusters, are investigated in detail. The
      influences of different magnetic fields on the beam pulse show similar to that of
      a single ion cluster. For increasing injection angles, the beam velocity
      perpendicular to the magnetic field increases, leading to increasing oscillations
      in the beam trajectory and energy deposition profile. Besides, the amount of
      energy that transferred from the beam pulse to the plasma increases as the beam
      injection velocity approaches the electron thermal velocity.

PMID- 22400684
TI  - Fast saturation of the two-plasmon-decay instability for shock-ignition
      conditions.
AB  - Two-plasmon-decay (TPD) instability is investigated for conditions relevant for
      the shock-ignition (SI) scheme of inertial confinement fusion. Two-dimensional
      particle-in-cell simulations show that in a hot, large-scale plasma, TPD develops
      in concomitance with stimulated Raman scattering (SRS). It is active only during
      the first picosecond of interaction, and then it is rapidly saturated due to
      plasma cavitation. TPD-excited plasma waves extend to small wavelengths, above
      the standard Landau cutoff. The hot electron spectrum created by SRS and TPD is
      relatively soft, limited to energies below 100 keV, which should not be a danger
      for the fuel core preheat in the SI scenario.

PMID- 22400685
TI  - Interaction of charged particles with localized electrostatic waves in a
      magnetized plasma.
AB  - Charged particle interaction with localized wave packets in a magnetic field is
      formulated using the canonical perturbation theory and the Lie transform theory.
      An electrostatic wave packet characterized by a wide range of group and phase
      velocities as well as spatial extent along and across the magnetic field is
      considered. The averaged changes in the momentum along the magnetic field, the
      angular momentum, and the guiding center position for an ensemble of particles
      due to their interaction with the wave packet are determined analytically. Both
      resonant and ponderomotive effects are included. For the case of a Gaussian wave
      packet, closed-form expressions include the dependency of the ensemble averaged
      particle momenta and guiding center position variations on wave packet parameters
      and particle initial conditions. These expressions elucidate the physics of the
      interaction which is markedly different from the well known case of particle
      interaction with plane waves and are relevant to a variety of applications
      ranging from space and astrophysical plasmas to laboratory and fusion plasmas, as
      well as accelerators and microwave devices.

PMID- 22400686
TI  - Energy deposition of multi-MeV protons in compressed targets of fast-ignition
      inertial confinement fusion.
AB  - The energy loss and penetration of multi-megelectronvolt protons into a uniform
      deuterium-tritium (DT) plasma has been calculated. The effects of nuclear elastic
      scattering and Coulomb interactions are treated from a unified point of view. In
      general, multiple scattering enhances the proton linear-energy transfer along the
      initial proton direction, thus the energy deposition increases near the end of
      its range. The net effect of multiple scattering is to reduce the penetration
      from 1.20 to 1.02 g cm-2 for 12 MeV protons in a rho=500 g cm-3 plasma at T=5
      keV. These results should have relevance to proton fast ignition, specifically to
      energy deposition calculations that critically assess quantitative ignition
      requirements.

PMID- 22400687
TI  - Coulomb double helical structure.
AB  - Structures of Coulomb clusters formed by dust particles in a plasma are studied
      by numerical simulation. Our study reveals the presence of various types of self
      organized structures of a cluster confined in a prolate spheroidal electrostatic
      potential. The stable configurations depend on a prolateness parameter for the
      confining potential as well as on the number of dust particles in a cluster. One
      dimensional string, two-dimensional zigzag structure and three-dimensional double
      helical structure are found as a result of the transition controlled by the
      prolateness parameter. The formation of stable double helical structures resulted
      from the transition associated with the instability of angular perturbations on
      double strings. Analytical perturbation study supports the findings of numerical
      simulations.

PMID- 22400688
TI  - Radiation-pressure-dominant acceleration: Polarization and radiation reaction
      effects and energy increase in three-dimensional simulations.
AB  - Polarization and radiation reaction (RR) effects in the interaction of a
      superintense laser pulse (I>10(23) W cm-2) with a thin plasma foil are
      investigated with three dimensional particle-in-cell (PIC) simulations. For a
      linearly polarized laser pulse, strong anisotropies such as the formation of two
      high-energy clumps in the plane perpendicular to the propagation direction and
      significant radiation reactions effects are observed. On the contrary, neither
      anisotropies nor significant radiation reaction effects are observed using
      circularly polarized laser pulses, for which the maximum ion energy exceeds the
      value obtained in simulations of lower dimensionality. The dynamical bending of
      the initially flat plasma foil leads to the self-formation of a quasiparabolic
      shell that focuses the impinging laser pulse strongly increasing its energy and
      momentum densities.

PMID- 22400689
TI  - Two-dimensional superfluid flows in inhomogeneous Bose-Einstein condensates.
AB  - We report an algorithm of constructing linear and nonlinear potentials in the two
      dimensional Gross-Pitaevskii equation subject to given boundary conditions, which
      allow for exact analytic solutions. The obtained solutions represent superfluid
      flows in inhomogeneous Bose-Einstein condensates. The method is based on the
      combination of the similarity reduction of the two-dimensional Gross-Pitaevskii
      equation to the one-dimensional nonlinear Schrodinger equation, the latter
      allowing for exact solutions, with the conformal mapping of the given domain,
      where the flow is considered, to a half space. The stability of the obtained
      flows is addressed. A number of stable and physically relevant examples are
      described.

PMID- 22400690
TI  - Solutions of the cylindrical nonlinear Maxwell equations.
AB  - Cylindrical nonlinear optics is a burgeoning research area which describes
      cylindrical electromagnetic wave propagation in nonlinear media. Finding new
      exact solutions for different types of nonlinearity and inhomogeneity to describe
      cylindrical electromagnetic wave propagation is of great interest and meaningful
      for theory and application. This paper gives exact solutions for the cylindrical
      nonlinear Maxwell equations and presents an interesting connection between the
      exact solutions for different cylindrical nonlinear Maxwell equations. We also
      provide some examples and discussion to show the application of the results we
      obtained. Our results provide the basis for solving complex systems of
      nonlinearity and inhomogeneity with simple systems.

PMID- 22400691
TI  - Controllable optical rogue waves in the femtosecond regime.
AB  - We derive analytical rogue wave solutions of variable-coefficient higher-order
      nonlinear Schrodinger equations describing the femtosecond pulse propagation via
      a transformation connected with the constant-coefficient Hirota equation. Then we
      discuss the propagation behaviors of controllable rogue waves, including
      recurrence, annihilation, and sustainment in a periodic distributed fiber system
      and an exponential dispersion decreasing fiber. Finally, we investigate nonlinear
      tunneling effects for rogue waves.

PMID- 22400692
TI  - Mesoscopic approach to granular crystal dynamics.
AB  - We present a mesoscopic approach to granular crystal dynamics, which comprises a
      three-dimensional finite-element model and a one-dimensional regularized contact
      model. The approach investigates the role of vibrational-energy trapping effects
      in the dynamic behavior of one-dimensional chains of particles in contact (i.e.,
      granular crystals), under small to moderate impact velocities. The only inputs of
      the models are the geometry and the elastic material properties of the individual
      particles that form the system. We present detailed verification results and
      validate the model comparing its predictions with experimental data. This
      approach provides a physically sound, first-principles description of dissipative
      losses in granular systems.

PMID- 22400693
TI  - Optimal spatiotemporal focusing through complex scattering media.
AB  - We present an alternative approach for spatiotemporal focusing through complex
      scattering media by wave front shaping. Using a nonlinear feedback signal to
      shape the incident pulsed wave front, we show that the limit of a spatiotemporal
      matched filter can be achieved; i.e., the wave amplitude at the intended time and
      focus position is maximized for a given input energy. It is exactly what is also
      achieved with time reversal. Demonstrated with ultrasound experiments, our method
      is generally applicable to all types of waves.

PMID- 22400694
TI  - Second-harmonic generation of cylindrical electromagnetic waves propagating in an
      inhomogeneous and nonlinear medium.
AB  - A general description of cylindrical electromagnetic waves propagating in
      nonlinear and inhomogeneous media is given by deducing cylindrical coupled-wave
      equations. Based on the cylindrical coupled-wave equations, we analyze second
      harmonic generation (SHG) of some special cases of inhomogeneity, and find that
      the inhomogeneity of the first- and second-order polarization can influence the
      amplitude of the SHG. From a different point of view, exact solutions of
      cylindrical electromagnetic waves propagating in a nonlinear medium with a
      special case of inhomogeneity have been obtained previously. We show that
      cylindrical SHG in an inhomogeneous and nonlinear medium can also be deduced from
      exact solutions. As verification, we compare the results obtained from the two
      different methods and find that descriptions of SHG by the coupled-wave equations
      are in good agreement with the exact solutions.

PMID- 22400695
TI  - General bounce-back scheme for concentration boundary condition in the lattice
      Boltzmann method.
AB  - In this paper, a general bounce-back scheme is proposed to implement
      concentration or thermal boundary conditions of convection-diffusion equation
      with the lattice Boltzmann method (LBM). Using this scheme, the general
      concentration boundary conditions, i.e., b1(?Cw/?n) + b2Cw = b3, can be easily
      implemented at boundaries with complex geometry structure like that in porous
      media. The numerical results obtained using the present scheme are in excellent
      agreement with the analytical solutions of flows with both stationary and moving
      interfaces. Furthermore, to better understand the halfway bounce-back scheme, an
      analytical study of the concentration jump is presented. The studies of
      theoretical analysis and numerical experiments demonstrate that the proposed
      scheme has second-order accuracy.

PMID- 22400696
TI  - Effectiveness of the statistical potential in the description of fermions in a
      worm-algorithm path-integral Monte Carlo simulation of 3He atoms placed on a 4He
      layer adsorbed on graphite.
AB  - We demonstrate the effectiveness of a statistical potential (SP) in the
      description of fermions in a worm-algorithm path-integral Monte Carlo simulation
      of a few 3He atoms floating on a 4He layer adsorbed on graphite. The SP in this
      work yields successful results, as manifested by the clusterization of 3He, and
      by the observation that the 3He atoms float on the surface of 4He. We display the
      positions of the particles in 3D coordinate space, which reveal clusterization of
      the 3He component. The correlation functions are also presented, which give
      further evidence for the clusterization.

PMID- 22400697
TI  - Discrete-element model for the interaction between ocean waves and sea ice.
AB  - We present a discrete-element method (DEM) model to simulate the mechanical
      behavior of sea ice in response to ocean waves. The interaction of ocean waves
      and sea ice potentially can lead to the fracture and fragmentation of sea ice
      depending on the wave amplitude and period. The fracture behavior of sea ice
      explicitly is modeled by a DEM method where sea ice is modeled by densely packed
      spherical particles with finite sizes. These particles are bonded together at
      their contact points through mechanical bonds that can sustain both tensile and
      compressive forces and moments. Fracturing naturally can be represented by the
      sequential breaking of mechanical bonds. For a given amplitude and period of
      incident ocean waves, the model provides information for the spatial distribution
      and time evolution of stress and microfractures and the fragment size
      distribution. We demonstrate that the fraction of broken bonds alpha increases
      with increasing wave amplitude. In contrast, the ice fragment size l decreases
      with increasing amplitude. This information is important for the understanding of
      the breakup of individual ice floes and floe fragment size.

PMID- 22400698
TI  - Lattice-type-dependent momentum-exchange method for moving boundaries.
AB  - The conventional momentum-exchange method (CME) is verified to be accurate for
      the stationary boundary by Mei et al. [Phys. Rev. E 65, 041203 (2002)], but it
      might be inaccurate when the boundary is moving in the lattice Boltzmann
      simulations. A lattice-type-dependent momentum-exchange method (LME) is presented
      to evaluate the hydrodynamic force on moving boundaries, in which the additional
      momenta induced by the type-changing lattices are well considered. LME preserves
      the superior features of CME, such as reliability, simplicity, and parallelism.
      Without any interpolation and integration, the algorithm is independent of
      boundary geometries, and therefore, efficient in computation and easy to be
      implemented in both two and three dimensions. A series of cylinder sedimentations
      are simulated to illustrate the accuracy and robustness of LME, and the results
      are in excellent agreement with those by the arbitrary Lagrangian-Eulerian
      technique (ALE). The lateral migrations of a particle are also investigated in
      the simulations of a neutrally buoyant cylinder in a Poiseuille flow, and
      consistent with the Segre-Silberberg effect.

PMID- 22400699
TI  - Solution of the time-dependent Schrodinger equation using time-dependent basis
      functions.
AB  - The time-dependent Schrodinger equation is solved by using an explicitly time
      dependent basis. This approach allows efficient reflection-free time propagation
      of the wave function. The applicability of the method is illustrated by solving
      various time-dependent problems including the calculation of the above threshold
      ionization of a model atom and the optical absorption spectrum of a sodium dimer.

PMID- 22400700
TI  - Taming hypersingular integrals using dimensional continuation.
AB  - We use the method of dimensional continuation to isolate singularities in
      integrals containing products of Green's functions or their derivatives. Rules
      for the extraction of the finite part of so-called hypersingular integrals are
      developed, which should be useful in methods based on boundary integral
      techniques in science and engineering. In applications to potential theory,
      electromagnetic scattering, and crack dynamics in continuum mechanics, boundary
      integrals now can be readily evaluated using computational techniques without
      recourse to complex analysis or contour distortions since the hypersingularities
      occurring in intermediate steps of the computations can be isolated and ignored
      while taking the finite parts of the integrals into account in a consistent
      manner. We have also identified new forms of the Dirac delta function in D
      dimensions, which are useful and convenient in the calculations. A summary of the
      integrable singular integrals is given in tabular form. We extend the
      considerations to a wider class of Green's functions and present a theorem, with
      additional results arising from it, that shows that hypersingular integrals
      associated with three-dimensional potential problems can be reduced to one
      dimensional finite integrals rather than two-dimensional integrals, again leading
      to direct evaluations in such cases. These calculations are compared with
      existing results to show the efficacy of the approach.

PMID- 22400701
TI  - Effect of nonlinearity in hybrid kinetic Monte Carlo-continuum models.
AB  - Recently there has been interest in developing efficient ways to model
      heterogeneous surface reactions with hybrid computational models that couple a
      kinetic Monte Carlo (KMC) model for a surface to a finite-difference model for
      bulk diffusion in a continuous domain. We consider two representative problems
      that validate a hybrid method and show that this method captures the combined
      effects of nonlinearity and stochasticity. We first validate a simple deposition
      dissolution model with a linear rate showing that the KMC-continuum hybrid agrees
      with both a fully deterministic model and its analytical solution. We then study
      a deposition-dissolution model including competitive adsorption, which leads to a
      nonlinear rate, and show that in this case the KMC-continuum hybrid and fully
      deterministic simulations do not agree. However, we are able to identify the
      difference as a natural result of the stochasticity coming from the KMC surface
      process. Because KMC captures inherent fluctuations, we consider it to be more
      realistic than a purely deterministic model. Therefore, we consider the KMC
      continuum hybrid to be more representative of a real system.

PMID- 22400702
TI  - Characterization of escape times of Josephson junctions for signal detection.
AB  - The measurement of the escape time of a Josephson junction might be used to
      detect the presence of a sinusoidal signal embedded in noise when use of standard
      signal processing tools can be prohibitive due to the extreme weakness of the
      source or to the huge amount of data. In this paper we show that the
      prescriptions for the experimental setup and some physical behaviors depend on
      the detection strategy. More specifically, by exploitation of the sample mean of
      escape times to perform detection, two resonant regions are identified. At low
      frequencies there is a stochastic resonance or activation phenomenon, while near
      the plasma frequency a geometric resonance appears. Furthermore, detection
      performance in the geometric resonance region is maximized at the prescribed
      value of the bias current. The naive sample mean detector is outperformed, in
      terms of error probability, by the optimal likelihood ratio test. The latter
      exhibits only geometric resonance, showing monotonically increasing performance
      as the bias current approaches the junction critical current. In this regime the
      escape times are vanishingly small and therefore performance is essentially
      limited by measurement electronics. The behavior of the likelihood ratio and
      sample mean detector for different values of incoming signal to noise ratio is
      discussed, and a relationship with the error probability is found. Detectors
      based on the likelihood ratio test could be employed also to estimate unknown
      parameters in the applied input signal. As a prototypical example we study the
      phase estimation problem of a sinusoidal current, which is accomplished by using
      the filter bank approach. Finally we show that for a physically feasible detector
      the performances are found to be very close to the Cramer-Rao theoretical bound.
      Applications might be found, for example, in some astronomical detection problems
      (where the all-sky gravitational and/or radio wave search for pulsars requires
      the analysis of nearly sinusoidal long-lived waveforms at very low signal-to
      noise ratio) or to analyze weak signals in the subterahertz range (where the
      traditional electronics counterpart is difficult to implement).

PMID- 22400703
TI  - Optimizing the accuracy of lattice Monte Carlo algorithms for simulating
      diffusion.
AB  - The behavior of a lattice Monte Carlo (LMC) algorithm (if it is designed
      correctly) must approach that of the continuum system that it is designed to
      simulate as the time step and the mesh step tend to zero. However, we show for an
      algorithm for unbiased particle diffusion that if one of these two parameters
      remains fixed, the accuracy of the algorithm is optimal for a certain finite
      value of the other parameter. In one dimension, the optimal algorithm with moves
      to the two nearest neighbor sites reproduces the correct second and fourth
      moments (and minimizes the error for the higher moments at large times) of the
      particle distribution and preserves the first two moments of the first-passage
      time distributions. In two and three dimensions, the same level of accuracy
      requires simultaneous moves along two axes ("diagonal" moves). Such moves
      attempting to cross an impenetrable boundary should be projected along the
      boundary, rather than simply rejected. We also treat the case of absorbing
      boundaries. We discuss the relation between optimally accurate LMC algorithms and
      a particular case of lattice Boltzmann (LB) algorithms for simulating diffusion
      and compare the computational efficiency of optimal LMC and optimal LB
      algorithms.

PMID- 22400704
TI  - Coupling lattice Boltzmann model for simulation of thermal flows on standard
      lattices.
AB  - In this paper, a coupling lattice Boltzmann (LB) model for simulating thermal
      flows on the standard two-dimensional nine-velocity (D2Q9) lattice is developed
      in the framework of the double-distribution-function (DDF) approach in which the
      viscous heat dissipation and compression work are considered. In the model, a
      density distribution function is used to simulate the flow field, while a total
      energy distribution function is employed to simulate the temperature field. The
      discrete equilibrium density and total energy distribution functions are obtained
      from the Hermite expansions of the corresponding continuous equilibrium
      distribution functions. The pressure given by the equation of state of perfect
      gases is recovered in the macroscopic momentum and energy equations. The coupling
      between the momentum and energy transports makes the model applicable for general
      thermal flows such as non-Boussinesq flows, while the existing DDF LB models on
      standard lattices are usually limited to Boussinesq flows in which the
      temperature variation is small. Meanwhile, the simple structure and general
      features of the DDF LB approach are retained. The model is tested by numerical
      simulations of thermal Couette flow, attenuation-driven acoustic streaming, and
      natural convection in a square cavity with small and large temperature
      differences. The numerical results are found to be in good agreement with the
      analytical solutions and/or other numerical results reported in the literature.

PMID- 22400705
TI  - Immersed boundary lattice Boltzmann model based on multiple relaxation times.
AB  - As an alterative version of the lattice Boltzmann models, the multiple relaxation
      time (MRT) lattice Boltzmann model introduces much less numerical boundary slip
      than the single relaxation time (SRT) lattice Boltzmann model if some special
      relationship between the relaxation time parameters is chosen. On the other hand,
      most current versions of the immersed boundary lattice Boltzmann method, which
      was first introduced by Feng and improved by many other authors, suffer from
      numerical boundary slip as has been investigated by Le and Zhang. To reduce such
      a numerical boundary slip, an immerse boundary lattice Boltzmann model based on
      multiple relaxation times is proposed in this paper. A special formula is given
      between two relaxation time parameters in the model. A rigorous analysis and the
      numerical experiments carried out show that the numerical boundary slip reduces
      dramatically by using the present model compared to the single-relaxation-time
      based model.

PMID- 22400706
TI  - Phase transition without global ordering in a hierarchical scale-free network.
AB  - We study the site-bond percolation on a hierarchical scale-free network, namely,
      the decorated (2,2)-flower, by using the renormalization group technique. The
      phase diagram essentially depends on the fraction of occupied sites.
      Surprisingly, when each site is unoccupied even with a small probability, the
      system permits neither the percolating phase nor the nonpercolating phase, but
      rather only critical phases. Although the order parameter always remains zero, a
      transition still exists between the critical phases that is characterized by the
      value of the fractal exponent, which measures the degree of criticality; the
      system changes from one critical state to another with the jump of the fractal
      exponent at the transition point. The phase boundary depends on the fraction of
      occupied sites. When the fraction of unoccupied sites exceeds a certain value,
      the transition line between the critical phases disappears, and a unique critical
      phase remains.

PMID- 22400707
TI  - Asymptotic diffusion coefficients and anomalous diffusion in a meandering jet
      flow under environmental fluctuations.
AB  - The nontrivial dependence of the asymptotic diffusion on noise intensity has been
      studied for a Hamiltonian flow mimicking the Gulf Jet Stream. Three different
      diffusion regimes have been observed depending on the noise intensity. For
      intermediate noise the asymptotic diffusion decreases with noise intensity at a
      rate which is linearly dependent to the flow's meander amplitude. Increasing the
      noise the fluid transport passes through a superdiffusive regime and finally
      becomes diffusive again at large noise intensities. The presence of inner
      circulation regimes in the flow has been found to be determinant to explain the
      observed behavior.

PMID- 22400708
TI  - Addendum to "Vibrations of a diamagnetically levitated water droplet".
AB  - We derive an analytical expression for the frequency of the shape oscillations of
      a diamagnetically levitated water droplet, in which the equilibrium shape is not
      spherical. We give the eigenfrequencies of all modes to first order in the
      oscillation amplitude and potential energy of the magnetogravitational trap
      confining the droplet. We compare the result with experimental measurements of
      the eigenfrequencies.

PMID- 22400709
TI  - Optical surface modes in the presence of nonlinearity and disorder.
AB  - We investigate numerically the effect of the competition of disorder,
      nonlinearity, and boundaries on the Anderson localization of light waves in
      finite-size, one-dimensional waveguide arrays. Using the discrete Anderson
      nonlinear Schrodinger equation, the propagation of the mode amplitudes up to some
      finite distance is monitored. The analysis is based on the calculated
      localization length and the participation number, two standard measures for the
      statistical description of Anderson localization. For relatively weak disorder
      and nonlinearity, a higher disorder strength is required to achieve the same
      degree of localization at the edge than in the interior of the array, in
      agreement with recent experimental observations in the linear regime. However,
      for relatively strong disorder and/or nonlinearity, this behavior is reversed and
      it is now easier to localize an excitation at the edge than in the interior.

PMID- 22400710
TI  - Mouse-adapted scrapie strains 139A and ME7 overcome species barrier to induce
      experimental scrapie in hamsters and changed their pathogenic features.
AB  - BACKGROUND: Transmissible spongiform encephalopathy (TSE) diseases are known to
      be zoonotic diseases that can infect different kinds of animals. The
      transmissibility of TSE, like that of other infectious diseases, shows marked
      species barrier, either being unable to infect heterologous species or difficult
      to form transmission experimentally. The similarity of the amino acid sequences
      of PrP among species is believed to be one of the elements in controlling the
      transmission TSE interspecies. Other factors, such as prion strains and host's
      microenvironment, may also participate in the process. METHODS: Two mouse-adapted
      strains 139A and ME7 were cerebrally inoculated to Golden hamsters. Presences of
      scrapie associate fibril (SAF) and PrPSc in brains of the infected animals were
      tested by TEM assays and Western blots dynamically during the incubation periods.
      The pathogenic features of the novel prions in hamsters, including
      electrophoretic patterns, glycosylating profiles, immunoreactivities, proteinase
      K-resistances and conformational stabilities were comparatively evaluated. TSE
      related neuropathological changes were assayed by histological examinations.
      RESULTS: After long incubation times, mouse-adapted agents 139A and ME7 induced
      experimental scrapie in hamsters, respectively, showing obvious spongiform
      degeneration and PrPSc deposits in brains, especially in cortex regions. SAF and
      PrPSc in brains were observed much earlier than the onset of clinical symptoms.
      The molecular characteristics of the newly-formed PrPSc in hamsters, 139A-ha and
      ME7-ha, were obviously distinct from the original mouse agents, however, greatly
      similar as that of a hamster-adapted scrapie strain 263 K. Although the
      incubation times and main disease signs of the hamsters of 139A-ha and ME7-ha
      were different, the pathogenic characteristics and neuropathological changes were
      highly similar. CONCLUSIONS: This finding concludes that mouse-adapted agents
      139A and ME7 change their pathogenic characteristics during the transmission to
      hamsters. The novel prions in hamsters' brains obtain new molecular properties
      with hamster-specificity.

PMID- 22400711
TI  - RF positivity has substantial influence on the peripheral memory B-cell
      compartment and its modulation by TNF inhibition.
AB  - OBJECTIVES: The role of B cells in rheumatoid arthritis (RA) has been well
      established with the advent of B-cell targeted therapies. Alterations of
      peripheral B-cell subsets in RA and heterogeneous modulations of the B-cell
      compartment under tumour necrosis factor (TNF) inhibition have been described. In
      this study we examined the influence of rheumatoid factor (RF) positivity on the
      peripheral B-cell compartment and its modulation under TNF blockade. METHODS:
      Consecutive patients with RA and inadequate response to methotrexate (MTX) were
      stratified according to RF status and a subset of them was included in a
      prospective study of weekly etanercept treatment. RESULTS: At baseline, RF
      negative patients had a significant higher percentage of overall CD27+ B cells
      compared to healthy controls (HC) and RF-positive patients. In detail, RF
      negative patients had 46.6% (range 15.7-86.8%) CD27+ B cells compared to 31.3%
      (12.9-56.9%, p = 0.026) in HC and 29.8% (19-73.3%, p = 0.04) in RF-positive
      patients. Within the CD27+ compartment, CD27+/immunoglobulin (Ig)D+ memory B
      cells were significantly increased to 26.4% (range 5.9-54.7%) in RF-negative
      patients compared to 14.9% (4.1-27.3%, p = 0.006) in HC and 10.5% (3.4-41.1%, p =
      0.003) in RF-positive patients. During anti-TNF therapy, memory B cells increased
      significantly in relative and absolute numbers only in RF-negative patients.
      CONCLUSIONS: In RF-negative patients, we observed an enhanced frequency of
      peripheral memory B cells and an accumulation of pre-switch memory B cells.
      During anti-TNF therapy, memory B cells increased significantly only in RF
      negative patients, suggesting that the peripheral memory B-cell compartment is
      more amenable to TNF inhibition in these patients.

PMID- 22400712
TI  - Comparative effectiveness research on patients with acute ischemic stroke using
      Markov decision processes.
AB  - BACKGROUND: Several methodological issues with non-randomized comparative
      clinical studies have been raised, one of which is whether the methods used can
      adequately identify uncertainties that evolve dynamically with time in real-world
      systems. The objective of this study is to compare the effectiveness of different
      combinations of Traditional Chinese Medicine (TCM) treatments and combinations of
      TCM and Western medicine interventions in patients with acute ischemic stroke
      (AIS) by using Markov decision process (MDP) theory. MDP theory appears to be a
      promising new method for use in comparative effectiveness research. METHODS: The
      electronic health records (EHR) of patients with AIS hospitalized at the 2nd
      Affiliated Hospital of Guangzhou University of Chinese Medicine between May 2005
      and July 2008 were collected. Each record was portioned into two "state-action
      reward" stages divided by three time points: the first, third, and last day of
      hospital stay. We used the well-developed optimality technique in MDP theory with
      the finite horizon criterion to make the dynamic comparison of different
      treatment combinations. RESULTS: A total of 1504 records with a primary diagnosis
      of AIS were identified. Only states with more than 10 (including 10) patients'
      information were included, which gave 960 records to be enrolled in the MDP
      model. Optimal combinations were obtained for 30 types of patient condition.
      CONCLUSION: MDP theory makes it possible to dynamically compare the effectiveness
      of different combinations of treatments. However, the optimal interventions
      obtained by the MDP theory here require further validation in clinical practice.
      Further exploratory studies with MDP theory in other areas in which complex
      interventions are common would be worthwhile.

PMID- 22400713
TI  - Structure-activity relationships and optimization of 3,5-dichloropyridine
      derivatives as novel P2X(7) receptor antagonists.
AB  - Screening of a library of chemical compounds showed that the dichloropyridine
      based analogue 9 was a novel P2X(7) receptor antagonist. To optimize its
      activity, we assessed the structure-activity relationships (SAR) of 9, focusing
      on the hydrazide linker, the dichloropyridine skeleton, and the hydrophobic acyl
      (R(2)) group. We found that the hydrazide linker and the 3,5-disubstituted
      chlorides in the pyridine skeleton were critical for P2X(7) antagonistic activity
      and that the presence of hydrophobic polycycloalkyl groups at the R(2) position
      optimized antagonistic activity. In the EtBr uptake assay in hP2X(7)-expressing
      HEK293 cells, the optimized antagonists, 51 and 52, had IC(50) values of 4.9 and
      13 nM, respectively. The antagonistic effects of 51 and 52 were paralleled by
      their ability to inhibit the release of the pro-inflammatory cytokine, IL-1beta,
      by LPS/IFN-gamma/BzATP stimulation of THP-1 cells (IC(50) = 1.3 and 9.2 nM,
      respectively). In addition, 52 strongly inhibited iNOS/COX-2 expression and NO
      production in THP-1 cells, further indicating that this compound blocks
      inflammatory signaling and suggesting that the dichloropyridine analogues may be
      useful in developing P2X(7) receptor targeted anti-inflammatory agents.

PMID- 22400714
TI  - Childhood bullying and the association with psychosis in non-clinical and
      clinical samples: a review and meta-analysis.
AB  - BACKGROUND: Approximately 11% of schoolchildren are bullied on a regular basis.
      It has been argued that continuous exposure to stress is related to the
      development of psychotic symptoms. The current study sought to investigate
      whether being bullied in childhood is related to the development of psychotic
      symptoms. METHOD: A search of PubMed, PsycINFO and EMBASE was conducted. The
      reference lists of included papers were searched to identify other eligible
      papers. A meta-analysis was performed on a subgroup of studies. RESULTS: We found
      four clinical and 10 general population studies that met inclusion criteria. The
      results of the clinical studies were mixed. However, the results of the non
      clinical studies provided more consistent evidence that school bullying is
      related to the development of non-clinical psychotic symptoms. Stronger
      associations were found with increased frequency and severity and longer duration
      of being bullied. We performed a meta-analysis on seven population-based studies,
      yielding unadjusted and adjusted odds ratios (ORs) of 2.7 [95% confidence
      interval (CI) 2.1-3.6] and 2.3 (95% CI 1.5-3.4) respectively. CONCLUSIONS:
      Although there is some evidence of an association between bullying and psychosis
      in clinical samples, the research is too sparse to draw any firm conclusions.
      However, population-based non-clinical studies support the role of bullying in
      the development of psychotic symptoms later in life. These findings are
      consistent with findings of an increased risk of psychotic symptoms among those
      exposed to other types of abuse.

PMID- 22400715
TI  - Osseointegration and biocompatibility of different metal implants--a comparative
      experimental investigation in sheep.
AB  - BACKGROUND: In the present study, 4 different metallic implant materials, either
      partly coated or polished, were tested for their osseointegration and
      biocompatibility in a pelvic implantation model in sheep. METHODS: Materials to
      be evaluated were: Cobalt-Chrome (CC), Cobalt-Chrome/Titanium coating (CCTC),
      Cobalt-Chrome/Zirconium/Titanium coating (CCZTC), Pure Titanium Standard (PTST),
      Steel, TAN Standard (TANST) and TAN new finish (TANNEW). Surgery was performed on
      7 sheep, with 18 implants per sheep, for a total of 63 implants. After 8 weeks,
      the specimens were harvested and evaluated macroscopically, radiologically,
      biomechanically (removal torque), histomorphometrically and histologically.
      RESULTS: Cobalt-Chrome screws showed significantly (p = 0.031) lower removal
      torque values than pure titanium screws and also a tendency towards lower values
      compared to the other materials, except for steel. Steel screws showed no
      significant differences, in comparison to cobalt-chrome and TANST, however also a
      trend towards lower torque values than the remaining materials. The results of
      the fluorescence sections agreed with those of the biomechanical test.
      Histomorphometrically, there were no significant differences of bone area between
      the groups. The BIC (bone-to-implant-contact), used for the assessment of the
      osseointegration, was significantly lower for cobalt-chrome, compared to steel (p
      = 0.001). Steel again showed a lower ratio (p = 0.0001) compared to the other
      materials. CONCLUSION: This study demonstrated that cobalt-chrome and steel show
      less osseointegration than the other metals and metal-alloys. However,
      osseointegration of cobalt-chrome was improved by zirconium and/or titanium based
      coatings (CCTC, TANST, TAN, TANNEW) being similar as pure titanium in their
      osseointegrative behavior.

PMID- 22400716
TI  - Evaluating the length of stay and value of time in a pediatric emergency
      department with two models by comparing two different albuterol delivery systems.
AB  - OBJECTIVE: Asthma is one of the most common childhood illnesses and accounts for
      a substantial amount of pediatric emergency department visits. Historically,
      acute exacerbations are treated with a beta agonist via nebulizer therapy (NEB).
      However, with the advent of the spacer, the medication can be delivered via a
      metered dose inhaler (MDI+S) with the same efficacy for mild-to-moderate asthma
      exacerbations. To date, no study has been done to evaluate emergency department
      (ED) length of stay (LOS) and opportunity cost between nebulized vs MDI+S. The
      objective of this study was to compare ED LOS and associated opportunity cost
      among children who present with a mild asthma exacerbation according to the
      delivery mode of albuterol: MDI+S vs NEB. METHODS: A structured, retrospective
      cross-sectional study was conducted. Medical records were reviewed from children
      aged 1-18 years treated at an urban pediatric ED from July 2007 to June 2008 with
      a discharge diagnosis International Classification of Disease-9 of asthma. Length
      of stay was defined: time from initial triage until the time of the guardian
      signature on the discharge instructions. An operational definition was used to
      define a mild asthma exacerbation; those patients requiring only one standard
      weight based albuterol treatment. Emergency department throughput time points,
      demographic data, treatment course, and delivery method of albuterol were
      recorded. RESULTS: Three hundred and four patients were analyzed: 94 in the MDI+S
      group and 209 in the NEB group. Mean age in years for the MDI+S group was 9.57 vs
      5.07 for the NEB group (p<0.001). The percentage of patients that received oral
      corticosteroids was 39.4% in the MDI+S group vs 61.7% in the NEB group (p<0.001).
      There was no difference between groups in: race, insurance status, gender, or
      chest radiographs. The mean ED LOS for patients in the MDI+S group was 170
      minutes compared to 205 minutes in the NEB group. On average, there was a 25.1
      minute time savings per patient in ED treatment time (p<0.001; 95% CI=3.8-31.7).
      Significant predictors of outcome for treatment time were chest radiograph,
      steroids, and treatment mode. Opportunity cost analysis estimated a potential
      cost savings of $213,532 annually using MDI+S vs NEB. CONCLUSION: In mild asthma
      exacerbations, administering albuterol via MDI+S decreases ED treatment time when
      compared to administering nebulized albuterol. A metered dose inhaler with spacer
      utilization may enhance opportunity cost savings and decrease the left without
      being seen population with improved throughput. LIMITATIONS: The key limitations
      of this study include its retrospective design, the proxy non-standard definition
      of mild asthma exacerbation, and the opportunity cost calculation, which may over
      estimate the value of ED time saved based on ED volume.

PMID- 22400717
TI  - India's vanishing birds.

PMID- 22400718
TI  - Ramsey fringes and time-domain multiple-slit interference from vacuum.
AB  - Sequences of alternating-sign time-dependent electric field pulses lead to
      coherent interference effects in Schwinger vacuum pair production, producing a
      Ramsey interferometer, an all-optical time-domain realization of the multiple
      slit interference effect, directly from the quantum vacuum. The interference,
      obeying fermionic quantum statistics, is manifest in the momentum dependence of
      the number of produced electrons and positrons along the linearly polarized
      electric field. The central value grows like N(2) for N pulses [i.e., N "slits"],
      and the functional form is well described by a coherent multiple-slit expression.
      This behavior is generic for many driven quantum systems.

PMID- 22400719
TI  - State-independent proof of Kochen-Specker theorem with 13 rays.
AB  - Quantum contextuality, as proved by Kochen and Specker, and also by Bell, should
      manifest itself in any state in any system with more than two distinguishable
      states and recently has been experimentally verified. However, for the simplest
      system capable of exhibiting contextuality, a qutrit, the quantum contextuality
      is verified only state dependently in experiment because too many (at least 31)
      observables are involved in all the known state-independent tests. Here we report
      an experimentally testable inequality involving only 13 observables that is
      satisfied by all noncontextual realistic models while being violated by all
      qutrit states. Thus our inequality facilitates a state-independent test of the
      quantum contextuality for an indivisible quantum system. We also provide a record
      breaking state-independent proof of the Kochen-Specker theorem with 13 directions
      determined by 26 points on the surface of a magic cube.

PMID- 22400720
TI  - Quantum nonlocality does not imply entanglement distillability.
AB  - Entanglement and nonlocality are both fundamental aspects of quantum theory, and
      play a prominent role in quantum information science. The exact relation between
      entanglement and nonlocality is, however, still poorly understood. Here we make
      progress in this direction by showing that, contrary to what previous work
      suggested, quantum nonlocality does not imply entanglement distillability.
      Specifically, we present analytically a 3-qubit entangled state that is separable
      along any bipartition. This implies that no bipartite entanglement can be
      distilled from this state, which is thus fully bound entangled. Then we show that
      this state nevertheless violates a Bell inequality. Our result also disproves the
      multipartite version of a long-standing conjecture made by Peres.

PMID- 22400721
TI  - Dephasing of multiparticle Rydberg excitations for fast entanglement generation.
AB  - An approach to fast entanglement generation based on Rydberg dephasing of
      collective excitations (spin waves) in large, optically thick atomic ensembles is
      proposed. Long-range 1/r(3) atomic interactions are induced by microwave mixing
      of opposite-parity Rydberg states. The required long coherence times are achieved
      via four-photon excitation and readout of long wavelength spin waves. The
      dephasing mechanism is shown to have favorable, approximately exponential,
      scaling for entanglement generation.

PMID- 22400722
TI  - Antibunched emission of photon pairs via quantum Zeno blockade.
AB  - We propose a new methodology, namely, the "quantum Zeno blockade," for managing
      light scattering at a few-photon level in general nonlinear-optical media, such
      as crystals, fibers, silicon microrings, and atomic vapors. Using this tool,
      antibunched emission of photon pairs can be achieved, leading to potent quantum
      optics applications such as deterministic entanglement generation without the
      need for heralding. In a practical implementation using an on-chip toroidal
      microcavity immersed in rubidium vapor, we estimate that high-fidelity entangled
      photons can be produced on-demand at MHz rates or higher, corresponding to an
      improvement of ?10(7) times from the state-of-the-art.

PMID- 22400723
TI  - Efficient entanglement criteria beyond Gaussian limits using Gaussian
      measurements.
AB  - We present a formalism to derive entanglement criteria beyond the Gaussian regime
      that can be readily tested by only homodyne detection. The measured observable is
      the Einstein-Podolsky-Rosen (EPR) correlation. Its arbitrary functional form
      enables us to detect non-Gaussian entanglement even when an entanglement test
      based on second-order moments fails. We illustrate the power of our
      experimentally friendly criteria for a broad class of non-Gaussian states under
      realistic conditions. We also show rigorously that quantum teleportation for
      continuous variables employs a specific functional form of EPR correlation.

PMID- 22400724
TI  - Thermodynamics of genuine nonequilibrium states under feedback control.
AB  - For genuine nonequilibrium states that even at fixed external control parameter
      exhibit dissipation, we extend the Hatano-Sasa equality to processes with
      feedback control. The resulting bound on the maximal extractable work is
      substantially sharper than what would follow from applying the Sagawa-Ueda
      equality to transitions involving such states. For repeated measurements at short
      enough intervals, the power thus extracted can even exceed the average cost of
      driving as demonstrated explicitly with a simple, analytically solvable example.

PMID- 22400725
TI  - Towards singularity- and ghost-free theories of gravity.
AB  - We present the most general covariant ghost-free gravitational action in a
      Minkowski vacuum. Apart from the much studied f(R) models, this includes a large
      class of nonlocal actions with improved UV behavior, which nevertheless recover
      Einstein's general relativity in the IR.

PMID- 22400726
TI  - Self-consistent evolution of magnetic fields and chiral asymmetry in the early
      universe.
AB  - We show that the evolution of magnetic fields in a primordial plasma, filled with
      standard model particles at temperatures T?10 MeV, is strongly affected by the
      chiral anomaly-an effect previously neglected. Although reactions, equilibrating
      left and right electrons, are in thermal equilibrium for T?80 TeV, a left-right
      asymmetry develops in the presence of strong magnetic fields. This results in
      magnetic helicity transfer from shorter to longer scales and lepton asymmetry
      present in the plasma until T~10 MeV, which may strongly affect many processes in
      the early Universe.

PMID- 22400729
TI  - Linearly polarized gluons and the Higgs transverse momentum distribution.
AB  - We study how gluons carrying linear polarization inside an unpolarized hadron
      contribute to the transverse momentum distribution of Higgs bosons produced in
      hadronic collisions. They modify the distribution produced by unpolarized gluons
      in a characteristic way that could be used to determine whether the Higgs boson
      is a scalar or a pseudoscalar particle.

PMID- 22400727
TI  - Evidence for direct CP violation in B+/-->etah+/- and observation of B0->etaK0.
AB  - We report measurements of the branching fractions and CP asymmetries for B(+/-)
      >etah(+/-) (h=K or pi) and the observation of the decay B(0)->etaK(0) from the
      final data sample of 772*10(6) B B pairs collected with the Belle detector at the
      KEKB asymmetric-energy e(+)e(-) collider. The measured branching fractions are
      B(B(+/-)->etaK(+/-))=(2.12+/-0.23+/-0.11)*10(-6), B(B(+/-)->etapi(+/-))=(4.07+/
      0.26+/-0.21)*10(-6), and B(B(0)->etaK(0))=(1.27(-0.29)(+0.33)+/-0.08)*10(-6),
      where the last decay is observed for the first time with a significance of 5.4
      standard deviations (sigma). We also find evidence for CP violation in the
      charged B modes, A(CP)(B(+/-)->etaK(+/-))=-0.38+/-0.11+/-0.01 and A(CP)(B(+/-)
      >etapi(+/-))=-0.19+/-0.06+/-0.01 with significances of 3.8 sigma and 3.0 sigma,
      respectively. For all measurements, the first and second uncertainties are
      statistical and systematic, respectively.

PMID- 22400730
TI  - Understanding jet scaling and jet vetos in Higgs searches.
AB  - Jet counting and jet vetos are crucial analysis tools for many LHC searches. We
      can understand their properties from the distribution of the exclusive number of
      jets. LHC processes tend to show either a distinct staircase scaling or a Poisson
      scaling, depending on kinematic cuts. We illustrate our approach in a detailed
      study of jets in weak boson fusion Higgs production.

PMID- 22400728
TI  - First observation of the P-wave spin-singlet bottomonium states hb(1P) and
      hb(2P).
AB  - We report the first observations of the spin-singlet bottomonium states h(b)(1P)
      and h(b)(2P). The states are produced in the reaction e(+)e(-)->h(b)(nP)pi(+)pi(
      ) using a 121.4 fb(-1) data sample collected at energies near the Upsilon(5S)
      resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-)
      collider. We determine M[h(b)(1P)]=(9898.2(-1.0-1.1)(+1.1+1.0)) MeV/c(2) and
      M[h(b)(2P)]=(10,259.8+/-0.6(-1.0)(+1.4)) MeV/c(2), which correspond to P-wave
      hyperfine splittings DeltaM(HF)=(+1.7+/-1.5) and (+0.5(-1.2)(+1.6)) MeV/c(2),
      respectively. The significances of the h(b)(1P) and h(b)(2P) are 5.5sigma and
      11.2sigma, respectively. We find that the production of the h(b)(1P) and h(b)(2P)
      is not suppressed relative to the production of the Upsilon(1S), Upsilon(2S), and
      Upsilon(3S).

PMID- 22400732
TI  - Next-to-leading-order results for five, six, and seven jets in electron-positron
      annihilation.
AB  - We present next-to-leading order corrections in the leading color approximation
      for jet rates in electron-positron annihilation up to seven jets. The results for
      the two-, three-, and four-jet rates agree with known results. The NLO jet rates
      have been known previously only up to five jets. The results for the six- and
      seven-jet rate are new. The results are obtained by a new and efficient method
      based on subtraction and numerical integration.

PMID- 22400733
TI  - Exploring the low-Z shore of the island of inversion at n=19.
AB  - The technique of invariant mass spectroscopy has been used to measure, for the
      first time, the ground state energy of neutron-unbound (28)F, determined to be a
      resonance in the (27)F+n continuum at 220(50) keV. States in (28)F were populated
      by the reactions of a 62 MeV/u (29)Ne beam impinging on a 288 mg/cm(2) beryllium
      target. The measured (28)F ground state energy is in good agreement with
      USDA/USDB shell model predictions, indicating that pf shell intruder
      configurations play only a small role in the ground state structure of (28)F and
      establishing a low-Z boundary of the island of inversion for N=19 isotones.

PMID- 22400734
TI  - Photon bubbles in ultracold matter.
AB  - We show that static and oscillating photon bubbles can be excited by diffused
      light in the laser cooled matter confined in a magneto-optical trap. The bubble
      instability is due to the coupling between the radiation field and the mean field
      oscillations of the ultracold gas, and it can provide a source for low frequency
      turbulence. We consider a diffusion-dominated regime, which can be described by a
      radiation transport equation, coupled with the mean field equations for the cold
      atom gas. A perturbative analysis shows the occurrence of two different regimes
      with either oscillating or purely growing bubbles. This work could also be useful
      to understand similar processes in astrophysics.

PMID- 22400735
TI  - Inelastic scattering of broadband electron wave packets driven by an intense
      midinfrared laser field.
AB  - Intense, 100 fs laser pulses at 3.2 and 3.6 MUm are used to generate, by
      multiphoton ionization, broadband wave packets with up to 400 eV of kinetic
      energy and charge states up to Xe(+6). The multiple ionization pathways are well
      described by a white electron wave packet and field-free inelastic cross
      sections, averaged over the intensity-dependent energy distribution for (e, ne)
      electron impact ionization. The analysis also suggests a contribution from a 4d
      core excitation, or giant resonance, in xenon.

PMID- 22400736
TI  - Competition of resonant and nonresonant paths in resonance-enhanced two-photon
      single ionization of He by an ultrashort extreme-ultraviolet pulse.
AB  - We theoretically study the pulse-width dependence of the photoelectron angular
      distribution (PAD) from the resonance-enhanced two-photon single ionization of He
      by femtosecond (?20 fs) extreme-ultraviolet pulses, based on the time-dependent
      perturbation theory and simulations with the full time-dependent Schrodinger
      equation. In particular, we focus on the competition between resonant and
      nonresonant ionization paths, which leads to the relative phase delta between the
      S and D wave packets distinct from the corresponding scattering phase shift
      difference. When the spectrally broadened pulse is resonant with an excited
      level, the competition varies with pulse width, and, therefore, delta and the PAD
      also change with it. On the other hand, when the Rydberg manifold is excited,
      delta and the PAD do not much vary with the pulse width, except for the very
      short-pulse regime.

PMID- 22400737
TI  - Threshold photodetachment in a repulsive potential.
AB  - We report on the first experimental observation of a new threshold behavior
      observed in the 5(2)G partial channel in photodetachment of K(-). It arises from
      the repulsive polarization interaction between the detached electron and the
      residual K(5(2)G) atom, which has a large negative dipole polarizability. In
      order to account for the observation in the K(5(2)G) channel, we have developed a
      semiclassical model that predicts an exponential energy dependence for the cross
      section. The measurements were made with collinear laser-ion beams and a
      resonance ionization detection scheme.

PMID- 22400738
TI  - Electron-energy bunching in laser-driven soft recollisions.
AB  - We introduce soft recollisions in laser-matter interaction. They are
      characterized by the electron missing the ion upon recollision in contrast with
      the well-known head-on collisions responsible for high-harmonic generation or
      above-threshold ionization. We demonstrate analytically that soft recollisions
      can cause a bunching of photoelectron energies through which a series of low
      energy peaks emerges in the electron yield along the laser polarization axis.
      This peak sequence is universal, it does not depend on the binding potential, and
      is found below an excess energy of one tenth of the ponderomotive energy.

PMID- 22400739
TI  - Absence of vacuum induced Berry phases without the rotating wave approximation in
      cavity QED.
AB  - We revisit earlier studies on Berry phases suggested to appear in certain cavity
      QED settings. It has been especially argued that a nontrivial geometric phase is
      achievable even in the situation of no cavity photons. We, however, show that
      such results hinge on imposing the rotating wave approximation (RWA), while
      without the RWA no Berry phases occur in these schemes. A geometrical
      interpretation of our results is obtained by introducing semiclassical energy
      surfaces which in a simple way brings out the phase-space dynamics. With the RWA,
      a conical intersection between the surfaces emerges and encircling it gives rise
      to the Berry phase. Without the RWA, the conical intersection is absent and
      therefore the Berry phase vanishes. It is believed that this is a first example
      showing how the application of the RWA in the Jaynes-Cummings model may lead to
      false conclusions, regardless of the mutual strengths between the system
      parameters.

PMID- 22400740
TI  - Observation of quantum motion of a nanomechanical resonator.
AB  - In this Letter we use resolved sideband laser cooling to cool a mesoscopic
      mechanical resonator to near its quantum ground state (phonon occupancy 2.6+/
      0.2), and observe the motional sidebands generated on a second probe laser.
      Asymmetry in the sideband amplitudes provides a direct measure of the
      displacement noise power associated with quantum zero-point fluctuations of the
      nanomechanical resonator, and allows for an intrinsic calibration of the phonon
      occupation number.

PMID- 22400741
TI  - Beam instabilities in the scale-free regime.
AB  - The instabilities arising in a one-dimensional beam sustained by the diffusive
      photorefractive nonlinearity in out-of-equilibrium ferroelectrics are
      theoretically and numerically investigated. In the "scale-free model," in
      striking contrast with the well-known spatial modulational instability, two
      different beam instabilities dominate: a defocusing and a fragmenting process.
      Both are independent of the beam power and are not associated with any specific
      periodic pattern.

PMID- 22400742
TI  - Ultrafast tilting of the dispersion of a photonic crystal and adiabatic spectral
      compression of light pulses.
AB  - We demonstrate, by theory and experiment, the ultrafast tilting of the dispersion
      curve of a photonic-crystal waveguide following the absorption of a femtosecond
      pump pulse. By shaping the pump-beam cross section with a nanometric shadow mask,
      different waveguide eigenmodes acquire different spatial overlap with the
      perturbing pump, leading to a local flattening of the dispersion by up to 11%. We
      find that such partial mode perturbation can be used to adiabatically compress
      the spectrum of a light pulse traveling through the waveguide.

PMID- 22400731
TI  - Evidence for spin correlation in t t production.
AB  - We present a measurement of the ratio of events with correlated t and t t spins
      to the total number of t t events. This ratio f is evaluated using a matrix
      element-based approach in 729 t t candidate events with a single lepton l
      (electron or muon) and at least four jets. The analyzed p p collisions data
      correspond to an integrated luminosity of 5.3 fb(-1) and were collected with the
      D0 detector at the Fermilab Tevatron collider operating at a center-of-mass
      energy ?s=1.96 TeV. Combining this result with a recent measurement of f in
      dileptonic final states, we find f in agreement with the standard model. In
      addition, the combination provides evidence for the presence of spin correlation
      in t t events with a significance of more than 3 standard deviations.

PMID- 22400743
TI  - All-optical measurement of high-harmonic amplitudes and phases in aligned
      molecules.
AB  - We report a new all-optical approach to measuring the phase and amplitude of high
      harmonic emission from aligned molecules. We combine the transient grating
      technique with a continuous rotation of the molecular alignment axis and develop
      an analytical model that enables the simultaneous determination of phases and
      amplitudes. Measurements in N(2) molecules are shown to be in qualitative
      agreement with the results of ab initio quantum scattering calculations.

PMID- 22400744
TI  - Spatiotemporal dispersion and wave envelopes with relativistic and
      pseudorelativistic characteristics.
AB  - A generic nonparaxial model for pulse envelopes is presented. Classic Schrodinger
      type descriptions of wave propagation have their origins in slowly-varying
      envelopes combined with a Galilean boost to the local time frame. By abandoning
      these two simplifications, a picture of pulse evolution emerges in which frame-of
      reference considerations and space-time transformations take center stage. A wide
      range of effects, analogous to those in special relativity, then follows for both
      linear and nonlinear systems. Explicit demonstration is presented through exact
      bright and dark soliton pulse solutions.

PMID- 22400745
TI  - Hamiltonian traffic dynamics in microfluidic-loop networks.
AB  - Recent microfluidic experiments revealed that large particles advected in a
      fluidic loop display long-range hydrodynamic interactions. However, the
      consequences of such couplings on the traffic dynamics in more complex networks
      remain poorly understood. In this Letter, we focus on the transport of a finite
      number of particles in one-dimensional loop networks. By combining numerical,
      theoretical, and experimental efforts, we evidence that this collective process
      offers a unique example of Hamiltonian dynamics for hydrodynamically interacting
      particles. In addition, we show that the asymptotic trajectories are necessarily
      reciprocal despite the microscopic traffic rules explicitly break the time
      reversal symmetry. We exploit these two remarkable properties to account for the
      salient features of the effective three-particle interaction induced by the
      exploration of fluidic loops.

PMID- 22400746
TI  - Parametrically excited water surface ripples as ensembles of oscillons.
AB  - We show that ripples on the surface of deep water which are driven parametrically
      by monochromatic vertical vibration represent ensembles of oscillating solitons,
      or quasiparticles, rather than waves. The horizontal mobility of oscillons
      determines the broadening of spectral lines and transitions from chaos to regular
      patterns. It is found that microscopic additions of proteins to water
      dramatically affect the oscillon mobility and drive transitions from chaos to
      order. The shape of the oscillons in physical space determines the shape of the
      frequency spectra of the surface ripple.

PMID- 22400747
TI  - Generation and characterization of electron bunches with ramped current profiles
      in a dual-frequency superconducting linear accelerator.
AB  - We report on the successful experimental generation of electron bunches with
      ramped current profiles. The technique relies on impressing nonlinear
      correlations in the longitudinal phase space using a superconducing radio
      frequency linear accelerator operating at two frequencies and a current-enhancing
      dispersive section. The produced ~700-MeV bunches have peak currents of the order
      of a kilo-Ampere. Data taken for various accelerator settings demonstrate the
      versatility of the method and, in particular, its ability to produce current
      profiles that have a quasilinear dependency on the longitudinal (temporal)
      coordinate. The measured bunch parameters are shown, via numerical simulations,
      to produce gigavolt-per-meter peak accelerating electric fields with transformer
      ratios larger than 2 in dielectric-lined waveguides.

PMID- 22400748
TI  - Proposal for an x-ray free electron laser oscillator with intermediate energy
      electron beam.
AB  - Harmonic lasing of low-gain free electron laser oscillators has been
      experimentally demonstrated in the terahertz and infrared regions. Recently, the
      low-gain oscillator has been reconsidered as a promising candidate for hard x-ray
      free electron lasers, through the use of high reflectivity, high-resolution x-ray
      crystals. In this Letter, it is proposed to utilize a crystal-based cavity
      resonant at a higher harmonic of the undulator radiation, together with phase
      shifting, to enable harmonic lasing of the x-ray free electron laser oscillator,
      and hence allow the generation of hard x-ray radiation at a reduced electron beam
      energy. Results show that fully coherent free electron laser radiation with
      megawatt peak power, in the spectral region of 10-25 keV, can be generated with a
      3.5 GeV electron beam.

PMID- 22400749
TI  - Ultracold electron bunch generation via plasma photocathode emission and
      acceleration in a beam-driven plasma blowout.
AB  - Beam-driven plasma wakefield acceleration using low-ionization-threshold gas such
      as Li is combined with laser-controlled electron injection via ionization of high
      ionization-threshold gas such as He. The He electrons are released with low
      transverse momentum in the focus of the copropagating, nonrelativistic-intensity
      laser pulse directly inside the accelerating or focusing phase of the Li blowout.
      This concept paves the way for the generation of sub-MUm-size, ultralow
      emittance, highly tunable electron bunches, thus enabling a flexible new class of
      an advanced free electron laser capable high-field accelerator.

PMID- 22400750
TI  - Universal nonlinear small-scale dynamo.
AB  - We consider astrophysically relevant nonlinear MHD dynamo at large Reynolds
      numbers (Re). We argue that it is universal in a sense that magnetic energy grows
      at a rate which is a constant fraction C(E) of the total turbulent dissipation
      rate. On the basis of locality bounds we claim that this "efficiency of the small
      scale dynamo", C(E), is a true constant for large Re and is determined only by
      strongly nonlinear dynamics at the equipartition scale. We measured C(E) in
      numerical simulations and observed a value around 0.05 in the highest resolution
      simulations. We address the issue of C(E) being small, unlike the Kolmogorov
      constant which is of order unity.

PMID- 22400751
TI  - Ping-pong modes: a new form of multipactor.
AB  - The multipactor is a vacuum discharge based on a secondary electron emission. A
      novel resonant form is proposed that combines one- and two-surface impacts within
      a single period, provided the total transit time is an odd number of rf half
      periods and the product of secondary yields exceeds unity. For low fD products,
      the simplest such mode is shown to significantly increase the upper electric
      field boundary of the multipacting region and lead to overlap of higher-order
      bands. The results agree nicely with 3D particle-in-cell code simulations.
      Practical implications of the findings are discussed.

PMID- 22400752
TI  - Nonlinear dispersion relation of geodesic acoustic modes.
AB  - The energy input and frequency shift of geodesic acoustic modes (GAMs) due to
      turbulence in tokamak edge plasmas are investigated in numerical two-fluid
      turbulence studies. Surprisingly, the turbulent GAM dispersion relation is
      qualitatively equivalent to the linear GAM dispersion but can have drastically
      enhanced group velocities. In up-down asymmetric geometry the energy input due to
      turbulent transport may favor the excitation of GAMs with one particular sign of
      the radial phase velocity relative to the magnetic drifts and may lead to pulsed
      GAM activity.

PMID- 22400753
TI  - Dielectric-barrier discharges in two-dimensional lattice potentials.
AB  - We use a pin-grid electrode to introduce a corrugated electrical potential into a
      planar dielectric-barrier discharge (DBD) system, so that the amplitude of the
      applied electric field has the profile of a two-dimensional square lattice. The
      lattice potential provides a template for the spatial distribution of plasma
      filaments in the system and has pronounced effects on the patterns that can form.
      The positions at which filaments become localized within the lattice unit cell
      vary with the width of the discharge gap. The patterns that appear when filaments
      either overfill or underfill the lattice are reminiscent of those observed in
      other physical systems involving 2D lattices. We suggest that the connection
      between lattice-driven DBDs and other areas of physics may benefit from the
      further development of models that treat plasma filaments as interacting
      particles.

PMID- 22400754
TI  - Nondiffusive suprathermal ion transport in simple magnetized toroidal plasmas.
AB  - We investigate suprathermal ion dynamics in simple magnetized toroidal plasmas in
      the presence of electrostatic turbulence driven by the ideal interchange
      instability. Turbulent fields from fluid simulations are used in the
      nonrelativistic equation of ion motion to compute suprathermal tracer ion
      trajectories. Suprathermal ion dispersion starts with a brief ballistic phase,
      during which particles do not interact with the plasma, followed by a turbulence
      interaction phase. In this one simple system, we observe the entire spectrum of
      suprathermal ion dynamics, from subdiffusion to superdiffusion, depending on beam
      energy and turbulence amplitude. We estimate the duration of the ballistic phase
      and identify basic mechanisms during the interaction phase that determine the
      dependencies of the character of suprathermal ion dispersion upon the beam energy
      and turbulence fluctuation amplitude.

PMID- 22400755
TI  - Observation of topologically stable 2D Skyrmions in an antiferromagnetic spinor
      Bose-Einstein condensate.
AB  - We present the creation and time evolution of two-dimensional Skyrmion
      excitations in an antiferromagnetic spinor Bose-Einstein condensate. Using a spin
      rotation method, the Skyrmion spin textures were imprinted on a sodium condensate
      in a polar phase, where the two-dimensional Skyrmion is topologically protected.
      The Skyrmion was observed to be stable on a short time scale of a few tens of ms
      but to dynamically deform its shape and eventually decay to a uniform spin
      texture. The deformed spin textures reveal that the decay dynamics involves
      breaking the polar phase inside the condensate without having topological charge
      density flow through the boundary of the finite-sized sample. We discuss the
      possible formation of half-quantum vortices in the deformation process.

PMID- 22400756
TI  - Mean-field dynamics of spin-orbit coupled Bose-Einstein condensates.
AB  - Spin-orbit coupling (SOC), the interaction between the spin and momentum of a
      quantum particle, is crucial for many important condensed matter phenomena. The
      recent experimental realization of SOC in neutral bosonic cold atoms provides a
      new and ideal platform for investigating spin-orbit coupled quantum many-body
      physics. In this Letter, we derive a generic Gross-Pitaevskii equation as the
      starting point for the study of many-body dynamics in spin-orbit coupled Bose
      Einstein condensates. We show that different laser setups for realizing the same
      SOC may lead to different mean-field dynamics. Various ground state phases
      (stripe, phase separation, etc.) of the condensate are found in different
      parameter regions. A new oscillation period induced by the SOC, similar to the
      Zitterbewegung oscillation, is found in the center-of-mass motion of the
      condensate.

PMID- 22400757
TI  - Improbability of void growth in aluminum via dislocation nucleation under typical
      laboratory conditions.
AB  - The rate at which dislocations nucleate from spherical voids subjected to shear
      loading is predicted from atomistic simulation. By employing the latest version
      of the finite temperature string method, a variational transition state theory
      approach can be utilized, enabling atomistic predictions at ordinary laboratory
      time scales, loads, and temperatures. The simulation results, in conjunction with
      a continuum model, show that the deformation and growth of voids in Al are not
      likely to occur via dislocation nucleation under typical loadings regardless of
      void size.

PMID- 22400758
TI  - Intermolecular hybridization governs molecular electrical doping.
AB  - Current models for molecular electrical doping of organic semiconductors are
      found to be at odds with other well-established concepts in that field, like
      polaron formation. Addressing these inconsistencies for prototypical systems, we
      present experimental and theoretical evidence for intermolecular hybridization of
      organic semiconductor and dopant frontier molecular orbitals. Common doping
      related observations are attributed to this phenomenon, and controlling the
      degree of hybridization emerges as a strategy for overcoming the present
      limitations in the yield of doping-induced charge carriers.

PMID- 22400759
TI  - Geometrical frustration and static correlations in a simple glass former.
AB  - We study the geometrical frustration scenario of glass formation for simple hard
      sphere models. We find that the dual picture in terms of defects brings little
      insight and no theoretical simplification for the understanding of the slowing
      down of relaxation, because of the strong frustration characterizing these
      systems. The possibility of a growing static length is furthermore found to be
      physically irrelevant in the regime that is accessible to computer simulations.

PMID- 22400760
TI  - Random and ordered phases of off-lattice rhombus tiles.
AB  - We study the covering of the plane by nonoverlapping rhombus tiles, a problem
      well studied only in the limiting case of dimer coverings of regular lattices. We
      go beyond this limit by allowing tiles to take any position and orientation on
      the plane, to be of irregular shape, and to possess different types of attractive
      interactions. Using extensive numerical simulations, we show that at large tile
      densities there is a phase transition from a fluid of rhombus tiles to a solid
      packing with broken rotational symmetry. We observe self-assembly of broken
      symmetry phases, even at low densities, in the presence of attractive tile-tile
      interactions. Depending on the tile shape and interactions, the solid phase can
      be random, possessing critical orientational fluctuations, or crystalline. Our
      results suggest strategies for controlling tiling order in experiments involving
      "molecular rhombi."

PMID- 22400761
TI  - Drop impact on superheated surfaces.
AB  - At the impact of a liquid droplet on a smooth surface heated above the liquid's
      boiling point, the droplet either immediately boils when it contacts the surface
      ("contact boiling"), or without any surface contact forms a Leidenfrost vapor
      layer towards the hot surface and bounces back ("gentle film boiling"), or both
      forms the Leidenfrost layer and ejects tiny droplets upward ("spraying film
      boiling"). We experimentally determine conditions under which impact behaviors in
      each regime can be realized. We show that the dimensionless maximum spreading
      gamma of impacting droplets on the heated surfaces in both gentle and spraying
      film boiling regimes shows a universal scaling with the Weber number We
      (gamma~We(2/5)), which is much steeper than for the impact on nonheated
      (hydrophilic or hydrophobic) surfaces (gamma~We(1/4)). We also
      interferometrically measure the vapor thickness under the droplet.

PMID- 22400762
TI  - Effective viscosity of confined hydrocarbons.
AB  - We present molecular dynamics friction calculations for confined hydrocarbon
      films with molecular lengths from 20 to 1400 carbon atoms. We find that the
      logarithm of the effective viscosity eta(eff) for nanometer-thin films depends
      linearly on the logarithm of the shear rate: log eta(eff)=C-nlog gamma, where n
      varies from 1 (solidlike friction) at very low temperatures to 0 (Newtonian
      liquid) at very high temperatures, following an inverse sigmoidal curve. Only the
      shortest chain molecules melt, whereas the longer ones only show a softening in
      the studied temperature interval 0<T<900 K. The results are important for the
      frictional properties of very thin (nanometer) films and to estimate their
      thermal durability.

PMID- 22400763
TI  - Quantum-mechanical interatomic potentials with electron temperature for strong
      coupling transition metals.
AB  - In narrow d-band transition metals, electron temperature T(el) can impact the
      underlying electronic structure for temperatures near and above melt, strongly
      coupling the ion- and electron-thermal degrees of freedom and producing T(el)
      dependent interatomic forces. Starting from the Mermin formulation of density
      functional theory, we have extended first-principles generalized pseudopotential
      theory to finite electron temperature and then developed efficient T(el)
      dependent model generalized pseudopotential theory interatomic potentials for a
      Mo prototype. Unlike potentials based on the T(el)=0 electronic structure, the
      T(el)-dependent model generalized pseudopotential theory potentials yield a high
      pressure Mo melt curve consistent with density functional theory quantum
      simulations, as well as with dynamic experiments, and also support a rich
      polymorphism in the high-(T,P) phase diagram.

PMID- 22400764
TI  - Charge Kondo anomalies in PbTe doped with Tl impurities.
AB  - We investigate the properties of PbTe doped with a small concentration x of Tl
      impurities acting as acceptors and described by Anderson impurities with negative
      onsite correlation energy. We use the numerical renormalization group method to
      show that the resulting charge Kondo effect naturally accounts for the unusual
      low temperature and doping dependence of normal state properties, including the
      self-compensation effect in the carrier density and the nonmagnetic Kondo anomaly
      in the resistivity. These are found to be in good qualitative agreement with
      experiment. Our results for the Tl s-electron spectral function provide a new
      interpretation of point contact data.

PMID- 22400765
TI  - Single impurity Anderson model versus density functional theory for describing Ce
      L3 x-ray absorption spectra of CeFe2: resolution of a recent controversy.
AB  - We resolved a recent controversy on the structure of the Ce L(3) x-ray absorption
      spectra (XAS) of CeFe(2); i.e., which of the single impurity Anderson model
      (SIAM) and the first-principles band calculations based on the density-functional
      theory (DFT) describes more appropriately the Ce 4f states and their contribution
      to the Ce L(3) XAS? For this purpose, we examined the core-hole effect in Ce L(3)
      XAS as an application of our new method taking advantage of resonant x-ray
      emission spectroscopy. Our result clearly shows that the Ce L(3) XAS structure is
      caused by the mixed valence 4f character revealed by the core-hole potential
      effect as indicated by SIAM, but denies the possibility that the L(3) XAS
      structure is caused by the 5d band structure with a very small core-hole effect
      as predicted by band calculations based on DFT.

PMID- 22400766
TI  - Correlated quantum transport of density wave electrons.
AB  - Recently observed Aharonov-Bohm quantum interference of the period h/2e in charge
      density wave rings strongly suggests that correlated density wave electron
      transport is a cooperative quantum phenomenon. The picture discussed here posits
      that quantum solitons nucleate and transport current above a Coulomb blockade
      threshold field. We propose a field-dependent tunneling matrix element and use
      the Schrodinger equation, viewed as an emergent classical equation as in
      Feynman's treatment of Josephson tunneling, to compute the evolving macrostate
      amplitudes, finding excellent quantitative agreement with voltage oscillations
      and current-voltage characteristics in NbSe(3). A proposed phase diagram shows
      the conditions favoring soliton nucleation versus classical depinning.

PMID- 22400768
TI  - Gutzwiller theory of band magnetism in LaOFeAs.
AB  - We use the Gutzwiller variational theory to calculate the ground-state phase
      diagram and quasiparticle bands of LaOFeAs. The Fe3d-As4p Wannier-orbital basis
      obtained from density-functional theory defines the band part of our eight-band
      Hubbard model. The full atomic interaction between the electrons in the iron
      orbitals is parametrized by the Hubbard interaction U and an average Hund's-rule
      interaction J. We reproduce the experimentally observed small ordered magnetic
      moment over a large region of (U,J) parameter space. The magnetically ordered
      phase is a stripe spin-density wave of quasiparticles.

PMID- 22400767
TI  - Backscattering suppression in supersonic 1D polariton condensates.
AB  - We investigate the effect of disorder on the propagation of one-dimensional
      polariton condensates in semiconductor microcavities. We observe a strong
      suppression of the backscattering produced by the imperfections of the structure
      when increasing the condensate density. This suppression occurs in the supersonic
      regime and is simultaneous to the onset of parametric instabilities which enable
      the "hopping" of the condensate through the disorder. Our results evidence a new
      mechanism for the strong scattering reduction of polaritons at high speeds.

PMID- 22400769
TI  - Gating the charge state of single molecules by local electric fields.
AB  - The electron-acceptor molecule TCNQ is found in either of two distinct integer
      charge states when embedded into a monolayer of a charge transfer complex on a
      gold surface. Scanning tunneling spectroscopy measurements identify these states
      through the presence or absence of a zero-bias Kondo resonance. Increasing the
      (tip-induced) electric field allows us to reversibly induce the oxidation or
      reduction of TCNQ species from their anionic or neutral ground state,
      respectively. We show that the different ground states arise from slight
      variations in the underlying surface potential, pictured here as the gate of a
      three-terminal device.

PMID- 22400770
TI  - Measuring the complex admittance of a carbon nanotube double quantum dot.
AB  - We investigate radio-frequency (rf) reflectometry in a tunable carbon nanotube
      double quantum dot coupled to a resonant circuit. By measuring the in-phase and
      quadrature components of the reflected rf signal, we are able to determine the
      complex admittance of the double quantum dot as a function of the energies of the
      single-electron states. The measurements are found to be in good agreement with a
      theoretical model of the device in the incoherent limit. In addition to being of
      fundamental interest, our results present an important step forward towards
      noninvasive charge and spin state readout in carbon nanotube quantum dots.

PMID- 22400771
TI  - Majorana modes in time-reversal invariant s-wave topological superconductors.
AB  - We present a time-reversal invariant s-wave superconductor supporting Majorana
      edge modes. The multiband character of the model together with spin-orbit
      coupling are key to realizing such a topological superconductor. We characterize
      the topological phase diagram by using a partial Chern number sum, and show that
      the latter is physically related to the parity of the fermion number of the time
      reversal invariant modes. By taking the self-consistency constraint on the s-wave
      pairing gap into account, we also establish the possibility of a direct
      topological superconductor-to-topological insulator quantum phase transition.

PMID- 22400772
TI  - Size of the localized electron emission sites on a closed multiwalled carbon
      nanotube.
AB  - We have measured the size of the localized electron emission sites on multiwalled
      carbon nanotubes (MWNTs) with caps closed by a fullerenelike structure. MWNTs
      were individually mounted on tungsten support tips and imaged with a field
      emission microscope (FEM). The magnification of the FEM was calibrated using
      electron ray tracing and verified by comparing transmission electron microscope
      images. The FEM image was also tested for effects of the lateral energy spread.
      We found ring-shaped emission areas with three flattened sides, of a radius of
      1.7+/-0.3 nm, and separated by 5+/-1 nm.

PMID- 22400773
TI  - Crossover between weak antilocalization and weak localization in a magnetically
      doped topological insulator.
AB  - We report transport studies on magnetically doped Bi(2)Se(3) topological
      insulator ultrathin films grown by molecular beam epitaxy. The magnetotransport
      behavior exhibits a systematic crossover between weak antilocalization and weak
      localization with the change of magnetic impurity concentration, temperature, and
      magnetic field. We show that the localization property is closely related to the
      magnetization of the sample, and the complex crossover is due to the
      transformation of Bi(2)Se(3) from a topological insulator to a topologically
      trivial dilute magnetic semiconductor driven by magnetic impurities. This work
      demonstrates an effective way to manipulate the quantum transport properties of
      the topological insulators by breaking time-reversal symmetry.

PMID- 22400774
TI  - Competing topological orders in the nu=12/5 quantum Hall state.
AB  - We provide numerical evidence that a p(x)-ip(y) paired Bonderson-Slingerland (BS)
      non-Abelian hierarchy state is a strong candidate for the observed nu=12/5
      quantum Hall plateau. We confirm the existence of a gapped incompressible nu=12/5
      quantum Hall state with shift S=2 on the sphere, matching that of the BS state.
      The exact ground state of the Coulomb interaction at S=2 is shown to have a large
      overlap with the BS trial wave function. Larger overlaps are obtained with BS
      type wave functions that are hierarchical descendants of general p(x)-ip(y)
      weakly paired states at nu=5/2. We perform a finite-size scaling analysis of the
      ground-state energies for nu=12/5 states at shifts corresponding to the BS (S=2)
      and 3-clustered Read-Rezayi (S=-2) universality classes. This analysis reveals
      very tight competition between these two non-Abelian topological orders.

PMID- 22400775
TI  - Non-Fraunhofer interference pattern in inhomogeneous ferromagnetic Josephson
      junctions.
AB  - Generic conditions are established for producing a non-Fraunhofer response of the
      critical supercurrent subject to an external magnetic field in ferromagnetic
      Josephson junctions. Employing the quasiclassical Keldysh-Usadel method, we
      demonstrate theoretically that an inhomogeneity in the magnitude of the energy
      scales in the system, including Thouless energy, exchange field and temperature
      gradient normal to the transport direction, influences drastically the standard
      Fraunhofer pattern. The exotic non-Fraunhofer response, similar to that observed
      in recent experiments, is described in terms of an intricate interplay between
      multiple "0-pi" states and is related to the appearance of proximity vortices.

PMID- 22400776
TI  - Unconventional anisotropic s-wave superconducting gaps of the LiFeAs iron
      pnictide superconductor.
AB  - We have performed high-resolution angle-resolved photoemission spectroscopy on Fe
      based superconductor LiFeAs (T(c)=18 K). We reveal multiple nodeless
      superconducting (SC) gaps with 2Delta/k(B)T(c) ratios varying from 2.8 to 6.4,
      depending on the Fermi surface (FS). We also succeeded in directly observing a
      gap anisotropy along the FS with magnitude up to ~30%. The anisotropy is fourfold
      symmetric with an antiphase between the hole and electron FSs, suggesting complex
      anisotropic interactions for the SC pairing. The observed momentum dependence of
      the SC gap offers an excellent opportunity to investigate the underlying pairing
      mechanism.

PMID- 22400777
TI  - Trapping and injecting single domain walls in magnetic wire by local fields.
AB  - A single domain wall (DW) moves at linearly increasing velocity under an
      increasing homogeneous drive magnetic field. Present experiments show that the DW
      is braked and finally trapped at a given position when an additional antiparallel
      local magnetic field is applied. That position and its velocity are further
      controlled by suitable tuning of the local field. In turn, the parallel local
      field of small amplitude does not significantly affect the effective wall speed
      at long distance, although it generates tail-to-tail and head-to-head pairs of
      walls moving along opposite directions when that field is strong enough.

PMID- 22400778
TI  - Coulombic quantum liquids in spin-1/2 pyrochlores.
AB  - We develop a nonperturbative gauge mean field theory (gMFT) method to study a
      general effective spin-1/2 model for magnetism in rare earth pyrochlores. gMFT is
      based on a novel exact slave-particle formulation, and matches both the
      perturbative regime near the classical spin ice limit and the semiclassical
      approximation far from it. We show that the full phase diagram contains two
      exotic phases: a quantum spin liquid and a Coulombic ferromagnet, both of which
      support deconfined spinon excitations and emergent quantum electrodynamics.
      Phenomenological properties of these phases are discussed.

PMID- 22400779
TI  - Femtosecond dynamics of the collinear-to-spiral antiferromagnetic phase
      transition in CuO.
AB  - We report on the ultrafast dynamics of magnetic order in a single crystal of CuO
      at a temperature of 207 K in response to strong optical excitation using
      femtosecond resonant x-ray diffraction. In the experiment, a femtosecond laser
      pulse induces a sudden, nonequilibrium increase in magnetic disorder. After a
      short delay ranging from 400 fs to 2 ps, we observe changes in the relative
      intensity of the magnetic ordering diffraction peaks that indicate a shift from a
      collinear commensurate phase to a spiral incommensurate phase. These results
      indicate that the ultimate speed for this antiferromagnetic reorientation
      transition in CuO is limited by the long-wavelength magnetic excitation
      connecting the two phases.

PMID- 22400781
TI  - Tunable resistivity of individual magnetic domain walls.
AB  - Despite the relevance of current-induced magnetic domain wall (DW) motion for new
      spintronics applications, the exact details of the current-domain wall
      interaction are not yet understood. A property intimately related to this
      interaction is the intrinsic DW resistivity. Here, we investigate experimentally
      how the resistivity inside a DW depends on the wall width Delta, which is tuned
      using focused ion beam irradiation of Pt/Co/Pt strips. We observe the nucleation
      of individual DWs with Kerr microscopy, and measure resistance changes in real
      time. A 1/Delta(2) dependence of DW resistivity is found, compatible with Levy
      Zhang theory. Also quantitative agreement with theory is found by taking full
      account of the current flowing through each individual layer inside the
      multilayer stack.

PMID- 22400780
TI  - Electron spin resonance shift in spin ladder compounds.
AB  - We analyze the effects of different coupling anisotropies in a spin-1/2 ladder on
      the electron spin resonance (ESR) shift. Combining a perturbative expression in
      the anisotropies with density matrix renormalization group computation of the
      short range correlations at finite temperature, we provide the full temperature
      and magnetic field evolution of the ESR paramagnetic shift. We show that for well
      chosen parameters the ESR shift can be in principle used to extract
      quantitatively the anisotropies and, as an example, discuss the material BPCB.

PMID- 22400782
TI  - Competing ferri- and antiferromagnetic phases in geometrically frustrated
      LuFe2O4.
AB  - We present a detailed study of magnetism in LuFe(2)O(4), combining magnetization
      measurements with neutron and soft x-ray diffraction. The magnetic phase diagram
      in the vicinity of T(N) involves a metamagnetic transition separating an
      antiferro- and a ferrimagnetic phase. For both phases the spin structure is
      refined by neutron diffraction. Observed diffuse magnetic scattering far above
      T(N) is explained in terms of near degeneracy of the magnetic phases.

PMID- 22400783
TI  - Mesoscopic self-collimation and slow light in all-positive index layered photonic
      crystals.
AB  - We demonstrate a mesoscopic self-collimation effect in photonic crystal
      superlattices consisting of a periodic set of all-positive index 2D photonic
      crystal and homogeneous layers. We develop an electromagnetic theory showing that
      diffraction-free beams are observed when the curvature of the optical dispersion
      relation is properly compensated for. This approach allows us to combine slow
      light regime together with self-collimation in photonic crystal superlattices
      presenting an extremely low filling ratio in air.

PMID- 22400784
TI  - Quantum and classical chirps in an anharmonic oscillator.
AB  - We measure the state dynamics of a tunable anharmonic quantum system, the
      Josephson phase circuit, under the excitation of a frequency-chirped drive. At
      small anharmonicity, the state evolves like a wave packet-a characteristic
      response in classical oscillators; in this regime, we report exponentially
      enhanced lifetimes of highly excited states, held by the drive. At large
      anharmonicity, we observe sharp steps, corresponding to the excitation of
      discrete energy levels. The continuous transition between the two regimes is
      mapped by measuring the threshold of these two effects.

PMID- 22400785
TI  - Resonant x-ray diffraction study of an unusually large phase coexistence in
      smectic liquid-crystal films.
AB  - The recent discovery of the new smectic-C(d6)(*) (SmC(d6)(*)) phase [S. Wang et
      al., Phys. Rev. Lett. 104, 027801 (2010)] also revealed the existence of a noisy
      region in the temperature window between the SmC(d6)(*) phase and the smectic
      C(d4)(*) (SmC(d4)(*)) phase. Characterized by multiple resonant peaks spanning a
      wide region in Q(Z), the corresponding structure of this temperature window has
      been a mystery. In this Letter, through a careful resonant x-ray diffraction
      study and simulations of the diffraction spectra, we show that this region is in
      fact an unusually large coexistence region of the SmC(d6)(*) phase and the
      SmC(d4)(*) phase. The structure of the noisy region is found to be a
      heterogeneous mixture of local SmC(d6)(*) and SmC(d4)(*) orders on the sub-MUm
      scale.

PMID- 22400786
TI  - Anisotropic pair correlations and structure factors of confined hard-sphere
      fluids: an experimental and theoretical study.
AB  - We address the fundamental question: how are pair correlations and structure
      factors of hard-sphere fluids affected by confinement between hard planar walls
      at close distance? For this purpose, we combine x-ray scattering from colloid
      filled nanofluidic channel arrays and first-principles inhomogeneous liquid-state
      theory within the anisotropic Percus-Yevick approximation. The experimental and
      theoretical data are in remarkable agreement at the pair-correlation level,
      providing the first quantitative experimental verification of the theoretically
      predicted confinement-induced anisotropy of the pair-correlation functions for
      the fluid. The description of confined fluids at this level provides, in the
      general case, important insights into the mechanisms of particle-particle
      interactions in dense fluids under confinement.

PMID- 22400787
TI  - Chemotaxis driven instability of a confined bacterial suspension.
AB  - A suspension of bacteria in a thin channel or film subject to a gradient in the
      concentration of a chemoattractant, will develop, in the absence of an imposed
      fluid flow, a steady bacteria concentration field that depends exponentially on
      cross-stream position. Above a critical bacteria concentration, this quiescent
      base state is unstable to a steady convective motion driven by the active
      stresses induced by the bacteria's swimming. Unlike previously identified long
      wavelength instabilities of active fluids, this instability results from coupling
      of the bacteria concentration field with the disturbance flow.

PMID- 22400788
TI  - Chiral quasicrystalline order and dodecahedral geometry in exceptional families
      of viruses.
AB  - On the example of exceptional families of viruses we (i) show the existence of a
      completely new type of matter organization in nanoparticles, in which the regions
      with a chiral pentagonal quasicrystalline order of protein positions are arranged
      in a structure commensurate with the spherical topology and dodecahedral
      geometry, (ii) generalize the classical theory of quasicrystals (QCs) to explain
      this organization, and (iii) establish the relation between local chiral QC order
      and nonzero curvature of the dodecahedral capsid faces.

PMID- 22400789
TI  - Fluctuations, dynamics, and the stretch-coil transition of single actin filaments
      in extensional flows.
AB  - Semiflexible polymers subject to hydrodynamic forcing play an important role in
      cytoskeletal motions in the cell, particularly when filaments guide molecular
      motors whose motions create flows. Near hyperbolic stagnation points, filaments
      experience a competition between bending elasticity and tension and are predicted
      to display suppressed thermal fluctuations in the extensional regime and a
      buckling instability under compression. Using a microfluidic cross-flow geometry,
      we verify these predictions in detail, including a fluctuation-rounded stretch
      coil transition of actin filaments.

PMID- 22400790
TI  - Rheology of ring polymer melts: from linear contaminants to ring-linear blends.
AB  - Ring polymers remain a challenge to our understanding of polymer dynamics.
      Experiments are difficult to interpret because of the uncertainty in the purity
      and dispersity of the sample. Using both equilibrium and nonequilibrium molecular
      dynamics simulations we have investigated the structure, dynamics, and rheology
      of perfectly controlled ring-linear polymer blends of chains of up to about 14
      entanglements per chain, comparable to experimental systems. Linear contaminants
      increase the zero-shear viscosity of a ring polymer melt by about 10% around one
      fifth of their overlap concentration. For equal concentrations of linear and ring
      polymers, the blend viscosity is about twice that of the pure linear melt. The
      diffusion coefficient of the rings decreases dramatically, while the linear
      polymers are mostly unaffected. Our results are supported by a primitive path
      analysis.

PMID- 22400791
TI  - Theory of thermally activated ionization and dissociation of bound states.
AB  - Calculating the microscopic dissociation rate of a bound state, such as a
      classical diatomic molecule, has been difficult so far. The problem was that
      standard theories require an energy barrier over which the bound particle (or
      state) escapes into the preferred low-energy state. This is not the case when the
      long-range repulsion responsible for the barrier is either absent or screened (as
      in Cooper pairs, plasmas, or biomolecular complexes). We solve this classical
      problem by accounting for entropic driving forces at the microscopic level. The
      theory predicts dissociation rates for arbitrary potentials and is successfully
      tested on the example of plasma, where it yields an estimate of ionization in the
      core of the Sun in excellent agreement with experiments. In biology, the new
      theory accounts for crowding in receptor-ligand kinetics and protein aggregation.

PMID- 22400792
TI  - Collective behavior of thermally active colloids.
AB  - Colloids with patchy metal coating under laser irradiation could act as local
      heat sources and generate temperature gradients that could induce self-propulsion
      and interactions between them. The collective behavior of a dilute solution of
      such thermally active particles is studied using a stochastic formulation. It is
      found that when the Soret coefficient is positive, the system could be described
      in a stationary state by the nonlinear Poisson-Boltzmann equation and could adopt
      density profiles with significant depletion in the middle region when confined.
      For colloids with a negative Soret coefficient, the system can be described as a
      dissipative equivalent of a gravitational system. It is shown that in this case
      the thermally active colloidal solution could undergo an instability at a
      critical laser intensity, which has similarities to a supernova explosion.

PMID- 22400793
TI  - No evidence of magnitude clustering in an aftershock sequence of nano- and
      picoseismicity.
AB  - One of the hallmarks of our current understanding of seismicity as highlighted by
      the epidemic-type-aftershock sequence model is that the magnitudes of earthquakes
      are independent of one another and can be considered as randomly drawn from the
      Gutenberg-Richter distribution. This assumption forms the basis of many
      approaches for forecasting seismicity rates and hazard assessment. Recently, it
      has been suggested that the assumption of independent magnitudes is not valid. It
      was subsequently argued that this conclusion was not supported by the original
      earthquake data from California. One of the main challenges is the lack of
      completeness of earthquake catalogs. Here, we study an aftershock sequence of
      nano- and picoseismicity as observed at the Mponeng mine, for which the issue of
      incompleteness is much less pronounced. We show that this sequence does not
      exhibit any significant evidence of magnitude correlations.

PMID- 22400794
TI  - Coexistence of cooperators and defectors in well mixed populations mediated by
      limiting resources.
AB  - Traditionally, resource limitation in evolutionary game theory is assumed just to
      impose a constant population size. Here we show that resource limitations may
      generate dynamical payoffs able to alter an original prisoner's dilemma, and to
      allow for the stable coexistence between unconditional cooperators and defectors
      in well-mixed populations. This is a consequence of a self-organizing process
      that turns the interaction payoff matrix into evolutionary neutral, and
      represents a resource-based control mechanism preventing the spread of defectors.
      To our knowledge, this is the first example of coexistence in well-mixed
      populations with a game structure different from a snowdrift game.

PMID- 22400795
TI  - Epidemiological and molecular analysis of a waterborne outbreak of norovirus
      GII.4.
AB  - Contaminated water is one of the main sources of norovirus (NoV) gastroenteritis
      outbreaks globally. Waterborne NoV outbreaks are infrequently attributed to GII.4
      NoV. In September 2009, a NoV outbreak affected a small school in Guangdong
      Province, China. Epidemiological investigations indicated that household use
      water, supplied by a well, was the probable source (relative risk 1.9). NoV
      nucleic acid material in concentrated well-water samples was detected using real
      time RT-PCR. Nucleotide sequences of NoV extracted from diarrhoea and well-water
      specimens were identical and had the greatest sequence identity to corresponding
      sequences from the epidemic strain GII.4-2006b. Our report documents the first
      laboratory-confirmed waterborne outbreak caused by GII.4 NoV genotype in China.
      Our investigations indicate that well water, intended exclusively for household
      use but not for consumption, caused this outbreak. The results of this report
      serve as a reminder that private well water intended for household use should be
      tested for NoV.

PMID- 22400796
TI  - Placental histologic criteria for diagnosis of cord accident: sensitivity and
      specificity.
AB  - "Cord accident" (compromised umbilical blood flow) as a cause of stillbirth is
      underreported, mainly due to a lack of diagnostic criteria. Based on fetal
      vascular pathology in the placenta, we have previously established histologic
      criteria for the diagnosis of cord accident. In the current study, we set out to
      test the sensitivity and specificity of these criteria by reviewing an
      independent set of stillbirth cases. Placental slides from 26 cases (in which
      cord accident was deemed the cause of death) and 62 controls (in which the cause
      of death was anything other than cord accident) were reviewed. The following
      histologic changes were noted: (1) dilated fetal vessels, (2) thrombosis in fetal
      vessels, and (3) avascular or near-avascular chorionic villi. "Minimal" criteria
      were defined as the presence of dilated and thrombosed fetal vessels, while the
      additional presence of focal or regional avascular or near-avascular villi
      satisfied the complete criteria. Of the 62 stillbirth controls with cause of
      death other than cord accident, 13 (21%) met the minimal criteria (specificity
      79%) and only 4 (6%) met the complete criteria for cord accident (specificity
      94%). In contrast, of the 26 cases with a cause of death related to cord
      accident, 16 met the minimal criteria (sensitivity 62%) and 12 met the complete
      criteria (sensitivity 46%). These histologic criteria identify cases of cord
      accident as a cause of stillbirth with very high specificity. This study confirms
      the utility of these criteria for diagnosis of cord accident and further stresses
      placental examination in evaluation of stillbirths.

PMID- 22400797
TI  - Uranyl-peroxide nanocapsules: electronic structure and cation complexation in
      [(UO2)20(MU-O2)30]20-.
AB  - The pentagonal K(10)[(UO(2))(5)(MU-O(2))(5)(C(2)O(4))(5)] species have been
      identified as the building blocks of uranyl-peroxide nanocapsules. The computed
      complexation energies of different alkali cations (Li(+), Na(+), K(+), Rb(+), and
      Cs(+)) with [(UO(2))(5)(MU-O(2))(5)(O(2))(5)](10-) and [(UO(2))(20)(MU
      O(2))(30)](20-) species suggest a strong cation templating effect. In the studied
      species, the largest complexation energy occurs for the experimentally used
      alkali cations (Na(+) and K(+)).

PMID- 22400799
TI  - Label-free catalytic and molecular beacon containing an abasic site for sensitive
      fluorescent detection of small inorganic and organic molecules.
AB  - In this work, two methods with complementary features, catalytic and molecular
      beacon (CAMB) and label-free fluorescent sensors using an abasic site, have been
      combined into new label-free CAMB sensors that possess advantages of each method.
      The label-free method using a dSpacer-containing molecular beacon makes CAMB more
      cost-effective and less interfering with the catalytic activity, while CAMB
      allows the label-free method to use true catalytic turnovers for signal
      amplifications, resulting in a new label-free CAMB sensor for Pb(2+) ion, with a
      detection limit of 3.8 nM while maintaining the same selectivity. Furthermore, by
      using CAMB to overcome the label-free method's limitation of requiring excess
      enzyme strands, a new label-free CAMB sensor using aptazyme is also designed to
      detect adenosine down to 1.4 MUM, with excellent selectivity over other
      nucleosides.

PMID- 22400800
TI  - Induced surface enhancement in coral Pt island films attached to nanostructured
      Ag electrodes.
AB  - Coral Pt islands films are deposited via electrochemical reduction on silica
      coated nanostructured Ag electrodes. From these devices surface-enhanced
      (resonance) Raman [SE(R)R] signals of molecules exclusively attached to Pt are
      obtained with intensity up to 50% of the value determined for Ag. SE(R)R
      spectroscopic investigations are carried out with different probe molecules,
      silica-coating thicknesses, and excitation lines. Additionally, field enhancement
      calculations on Ag-SiO(2)-Pt support geometries are performed to elucidate the
      influence of the Pt island film nanostructure on the observed Raman intensities.
      It is concluded that the nonperfect coating of the Pt island film promotes the
      efficiency of the induced Pt SER activity. Comparison with similar measurements
      on Ag-SiO(2)-Au electrodes further suggests that the chemical nature of the
      deposited metal island film plays a minor role for the SE(R)R intensity.

PMID- 22400801
TI  - Micronucleus frequency in children exposed to biomass burning in the Brazilian
      Legal Amazon region: a control case study.
AB  - BACKGROUND: The Amazon represents an area of 61% of Brazilian territory and is
      undergoing major changes resulting from disorderly economic development,
      especially the advance of agribusiness. Composition of the atmosphere is
      controlled by several natural and anthropogenic processes, and emission from
      biomass burning is one with the major impact on human health. The aim of this
      study was to evaluate genotoxic potential of air pollutants generated by biomass
      burning through micronucleus assay in exfoliated buccal cells of schoolchildren
      in the Brazilian Amazon region. METHODS: The study was conducted during the dry
      seasons in two regions of the Brazilian Amazon. The assay was carried out on
      buccal epithelial cells of 574 schoolchildren between 6-16 years old. RESULTS:
      The results show a significant difference between micronucleus frequencies in
      children exposed to biomass burning compared to those in a control area.
      CONCLUSIONS: The present study demonstrated that in situ biomonitoring using a
      sensitive and low cost assay (buccal micronucleus assay) may be an important tool
      for monitoring air quality in remote regions. It is difficult to attribute the
      increase in micronuclei frequency observed in our study to any specific toxic
      element integrated in the particulate matters. However, the contribution of the
      present study lies in the evidence that increased exposure to fine particulate
      matter generates an increased micronuclei frequency in oral epithelial cells of
      schoolchildren.

PMID- 22400802
TI  - The foot-health of people with diabetes in a regional Australian population: a
      prospective clinical audit.
AB  - BACKGROUND: There is limited understanding of the foot-health of people with
      diabetes in Australian regional areas. The aim of this study was to document the
      foot-health of people with diabetes who attend publically funded podiatric
      services in a regional Australian population. METHODS: A three month prospective
      clinical audit was undertaken by the publically-funded podiatric services of a
      large regional area of Victoria, Australia. The primary variables of interest
      were the University of Texas (UT) diabetic foot risk classification of each
      patient and the incidence of new foot ulceration during the study period. Age,
      gender, diabetes type, duration of diabetes and the podiatric service the
      patients attended were the other variables of interest. RESULTS: Five hundred and
      seventy six patients were seen during the three month period. Over 49% had a UT
      risk classification at a level at least peripheral neuropathy or more serious
      diabetes-related foot morbidity. Higher risk at baseline was associated with
      longer duration of diabetes (F = 31.7, p < 0.001), male gender (chi2 = 40.3, p
      <0.001) and type 1 diabetes (chi2 = 37.3, p <0.001). A prior history of foot
      pathology was the overwhelming predictor for incident ulceration during the time
      period (OR 8.1 (95% CI 3.6 to 18.2), p < 0.001). CONCLUSIONS: The publically
      funded podiatric services of this large regional area of Australia deal with a
      disproportionally large number of people with diabetes at high risk of future
      diabetes-related foot complications. These findings may be useful in ensuring
      appropriate allocation of resources for future public health services involved in
      diabetic foot health service delivery in regional areas.

PMID- 22400803
TI  - Aryne insertion into I-I sigma-bonds.
AB  - A new protocol for the efficient synthesis of o-diiodoarenes has been developed.
      This method allows the synthesis of substituted and polycyclic o-diiodoarenes,
      which are difficult to obtain by classical methods. This diiodination process
      involves the formal insertion of arynes into the I-I sigma-bond.

PMID- 22400805
TI  - Serous cystadenocarcinoma of the pancreas: report of a case and management
      reflections.
AB  - BACKGROUND: Serous adenomas represent 1-2% of pancreatic neoplasms and typically
      are asymptomatic not requiring any treatment and simple observation is the option
      of choice. Although, they carry a realistic risk of malignancy despite the
      general view that they never become malignant. We report a case, which, according
      to our best knowledge is the 27th case reported in the literature. METHODS: We
      reviewed the literature by performing a search in Pub Med and Medline. RESULTS: A
      86-year old patient known to have a serous cystadenoma of the pancreas treated
      conservatively through a close clinical and radiological follow up which was
      unattended for 4 years ending up to our emergency department suffering an acute
      abdomen. Exploratory laparotomy revealed a perforated prepyloric ulcer which was
      treated accordingly. Patient died some weeks later due to severe medical co
      morbidities. CONCLUSION: Serous cystic neoplasms of the pancreas carry a
      realistic risk of malignancy despite the general view that they never become
      malignant. In our opinion the treatment strategy of serous cystic neoplasms of
      the pancreas should be aggressive even in cases of remote metastases since
      prognosis of the disease is satisfactory.

PMID- 22400804
TI  - Translational investigation and treatment of neuropathic pain.
AB  - Neuropathic pain develops from a lesion or disease affecting the somatosensory
      system. Translational investigations of neuropathic pain by using different
      animal models reveal that peripheral sensitization, spinal and cortical
      plasticity may play critical roles in neuropathic pain. Furthermore, descending
      facilitatory or excitatory modulation may also act to enhance chronic pain.
      Current clinical therapy for neuropathic pain includes the use of pharmacological
      and nonpharmacological (psychological, physical, and surgical treatment) methods.
      However, there is substantial need to better medicine for treating neuropathic
      pain. Future translational researchers and clinicians will greatly facilitate the
      development of novel drugs for treating chronic pain including neuropathic pain.

PMID- 22400806
TI  - Licochalcone a inhibits lipopolysaccharide-induced inflammatory response in vitro
      and in vivo.
AB  - Licochalcone A (Lico A), a flavonoid found in licorice root (Glycyrrhiza glabra),
      is known for its antimicrobial activity and its reported ability to inhibit
      cancer cell proliferation. In the present study, we found that Lico A exerted
      potent anti-inflammatory effects in in vitro and in vivo models induced by
      lipopolysaccharide (LPS). The concentrations of TNF-alpha, interleukin (IL)-6,
      and IL-1beta in the culture supernatants of RAW 264.7 cells were determined at
      different time points following LPS administration. LPS (0.5 mg/kg) was instilled
      intranasally (i.n.) in phosphate-buffered saline to induce acute lung injury, and
      24 h after LPS was given, bronchoalveolar lavage fluid was obtained to measure
      pro-inflammatory mediator and total cell counts. The phosphorylation of mitogen
      activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-kappaB) p65
      protein was analyzed by Western blotting. Our results showed that Lico A
      significantly reduced the amount of inflammatory cells, the lung wet-to-dry
      weight (W/D) ratio, protein leakage, and myeloperoxidase activity and enhances
      oxidase dimutase activity in mice with LPS-induced acute lung injury (ALI).
      Enzyme-linked immunosorbent assay results indicated that Lico A can significantly
      down-regulate TNF-alpha, IL-6, and IL-1beta levels in vitro and in vivo, and
      treatment with Lico A significantly attenuated alveolar wall thickening, alveolar
      hemorrhage, interstitial edema, and inflammatory cells infiltration in mice with
      ALI. In addition, we further demonstrated that Lico A exerts an anti-inflammation
      effect in an in vivo model of acute lung injury through suppression of NF-kappaB
      activation and p38/ERK MAPK signaling in a dose-dependent manner.

PMID- 22400808
TI  - Advancement in multifunctional nanoparticles for the effective treatment of
      cancer.
AB  - INTRODUCTION: Nanotechnology has gained wider importance for the treatment of
      various diseases, including cancer. Multifunctional or theranostic agents are
      emerging as promising therapeutic paradigms, which provide attractive vehicles
      for both image and therapeutic agents. Nanosystems are capable of diagnosis,
      specific targeted drug therapy and monitoring therapeutic response. Due to their
      well-developed surface nature, nanomolecules are easy to anchor with
      multifunctional groups. AREAS COVERED: The present review aims to give an
      extensive account on the progress of multifunctional nanoparticles throughout the
      blooming research with regards to their clinical application in cancer. This
      paper discusses graphene, a newly developed multifunctional vehicle in
      nanotechnology. Furthermore, it focuses on the development of tumor cells, the
      advantages of novel multifunctional nanoparticles over traditional methods and
      the use of nanoparticles in cancer therapy. In addition, patents issued by the US
      office are also included. EXPERT OPINION: Despite numerous advantages,
      multifunctional nanoparticles are still at an infancy stage. Many great
      achievements have been attained in this field to date, but many challenges still
      remain. A problem that limits the use of multifunctional nanoparticles is
      toxicity. If this toxicity can be overcome then the advancement in nanocomposite
      material science will be well on the way to a prospective treatment of cancer.

PMID- 22400807
TI  - Dome-type carcinoma of the colon; a rare variant of adenocarcinoma resembling a
      submucosal tumor: a case report.
AB  - BACKGROUND: Dome-type carcinoma (DC) is a distinct variant of colorectal
      adenocarcinoma and less than 10 cases have been described in the literature. Most
      of the previously reported cases were early lesions and no endoscopic
      observations have been described so far. We herein report a case of a DC invading
      the subserosal layer, including endoscopic findings. CASE PRESENTATION: A highly
      elevated lesion in the transverse colon was diagnosed by colonoscopy in a 77-year
      old man. The tumor appeared to be similar to a submucosal tumor (SMT), however, a
      demarcated area of reddish and irregular mucosa was observed at the top of the
      tumor. There were no erosions or ulcers. Laparoscopic-assisted right
      hemicolectomy was performed and pathological examination revealed a well
      circumscribed tumor invading the subserosal layer. The tumor was a well
      differentiated adenocarcinoma associated with a dense lymphocytic infiltration
      and showed expansive growth. The overlying mucosal layer showed high-grade
      dysplasia. CONCLUSION: The present lesion was diagnosed as a DC of the colon
      invading the subserosal layer. Because the association of mucosal dysplasia is
      common in DCs, the detection of dysplastic epithelium would be important to
      discriminate DCs from SMTs.

PMID- 22400809
TI  - Chemical constituents comparison between Rhizoma Smilacis Glabrae and Rhizoma
      Smilacis Chinae by HPLC-DAD-MS/MS.
AB  - Rhizoma Smilacis Glabrae (RSG) and Rhizoma Smilacis Chinae (RSC) are two herbal
      materials that belong to the same genera and are both listed in the Chinese
      Pharmacopoeia. Chemical constituents in the two species were compared by HPLC-DAD
      MS/MS. Many common constituents were found in both species, including shikimic
      acid, 5-O-caffeoylshikimic acid, trans-resveratrol, taxifolin, astilbin and its
      three stereoisomers, engeletin and isoengeletin. However, syringic acid was found
      only in RSG, while chlorogenic acid was found only in RSC.

PMID- 22400811
TI  - Synthesis and evaluation of (2-(4-methoxyphenyl)-4-quinolinyl)(2
      piperidinyl)methanol (NSC23925) isomers to reverse multidrug resistance in
      cancer.
AB  - Development of multidrug resistance (MDR) during chemotherapy is a fundamental
      obstacle associated with cancer care. Prior studies have identified (2-(4
      methoxyphenyl)-4-quinolinyl)(2-piperidinyl)methanol (5) (NSC23925) to be a small
      molecule agent that reverses MDR in cancer cells. We synthesized all four isomers
      of 5 and analyzed them by liquid chromatography-mass spectrometry (LCMS).
      Structure-activity relationships for reversing MDR were evaluated. Isomer 11
      demonstrated the most potent activity. 11 reversed MDR in several drug-resistant
      cell lines expressing Pgp, including ovarian, breast, colon, uterine, and sarcoma
      cancer. 11 resensitized these cell lines to paclitaxel, doxorubicin,
      mitoxantrone, vincristine, and trabectedin with no effect on cell sensitivity to
      cisplatin, topotecan, and methotrexate. 11 significantly enhanced in vivo
      antitumor activity of paclitaxel in MDR xenograft models, without increasing the
      level of paclitaxel toxicity. In conclusion, 11 and derivatives of this compound
      may hold therapeutic value in the treatment of MDR-dependent cancers.

PMID- 22400810
TI  - Extended-release niacin/laropiprant effects on lipoprotein subfractions in
      patients with type 2 diabetes mellitus.
AB  - BACKGROUND: A potentially atherogenic lipid profile often found in patients with
      type 2 diabetes mellitus (T2DM) includes increased concentrations of small, low
      density lipoprotein (LDL) and intermediate-density lipoprotein (IDL) and
      decreased concentration of medium/large high-density lipoprotein (HDL) particles.
      Extended-release niacin/laropiprant (ERN/LRPT) lowers LDL-cholesterol (LDL-C) and
      triglycerides (TG), and raises HDL cholesterol (HDL-C) levels with attenuation of
      niacin-induced flushing. METHODS: Plasma HDL, LDL, IDL, very-low-density
      lipoprotein (VLDL), and chylomicron particle concentration and size at were
      evaluated at baseline and week 12 using nuclear magnetic resonance (NMR). The
      data were acquired from a randomized, multicenter, double-blind, placebo
      controlled study including 796 patients with T2DM treated with either 1 tablet of
      ERN 1 gram/LRPT 20 mg or matching placebo daily, increased after 4 weeks to 2
      tablets daily. RESULTS: ERN/LRPT significantly (P<=0.001 for all) reduced LDL-C
      17.9% and TG 23.1%, and increased HDL-C levels 23.2%. Compared to placebo,
      ERN/LRPT decreased LDL, IDL, VLDL, and chylomicron particle concentrations
      [median concentration of smallest LDL particles decreased 16.6%, 95% confidence
      interval (CI) -22.3, -10.9, whereas the largest LDL particles decreased 11.0%,
      95% CI -18.7, -3.2, and total VLDL/chylomicron mean plasma particle concentration
      decreased 34.7%, 95% CI -41.3, -28.1]. Compared to placebo, ERN/LRPT shifted the
      distribution of HDL particle diameter from smaller to larger (median
      concentration of the largest HDL particles increased 32.7% (95% CI 25.30, 40.58),
      whereas concentration of the smallest HDL particles decreased 8.2% (95% CI 
      11.29, -5.06). CONCLUSIONS: Compared with placebo in patients with T2DM, ERN/LRPT
      shifted the lipoprotein profile toward a potentially less atherogenic pattern
      with reduced atherogenic LDL and IDL particle concentrations, and increased large
      HDL plasma particle concentrations. (ClinicalTrials.gov: NCT00485758).

PMID- 22400812
TI  - Sonographic and clinical pattern of extracranial and cranial giant cell
      arteritis.
AB  - OBJECTIVES: The aim of our study was to describe the sonographic pattern and
      clinical manifestations of extracranial (i.e. carotid and proximal arm arteries)
      and cranial arterial involvement in patients with giant cell arteritis (GCA).
      METHODS: One hundred and ten consecutive patients with an established diagnosis
      of GCA between January 2002 and June 2010 were identified retrospectively from a
      database. All patients underwent colour duplex sonography (CDS) of the
      superficial temporal, carotid, and proximal arm arteries at the time of
      diagnosis. Circumferential, homogeneous, hypoechogenic wall thickening was
      regarded as a typical sign for GCA. Sonographic and clinical characteristics of
      patients with and without extracranial vessel involvement were compared. RESULTS:
      Extracranial GCA was observed in 59 of 110 subjects (53.6%). The axillary artery
      (48.2%) was most frequently affected and bilateral vessel involvement was present
      in almost all patients (94.8%). Compared to patients with cranial GCA, patients
      with extracranial GCA were significantly younger, frequently did not meet the
      American College of Rheumatology (ACR) criteria for classification of cranial
      GCA, exhibited a lower rate of permanent visual impairment, and were diagnosed
      later after onset of clinical symptoms (all p < 0.01). With increasing age, a
      continuous shift from GCA with extracranial arterial involvement to cranial GCA
      was observed. CONCLUSION: Using CDS, extracranial GCA is a common finding, most
      frequently observed in the axillary arteries. The clinical pattern of GCA with
      extracranial arterial involvement differs from that of cranial GCA.

PMID- 22400813
TI  - Lung injury in preterm neonates: the role and therapeutic potential of stem
      cells.
AB  - Continuous improvements in perinatal care have allowed the survival of ever more
      premature infants, making the task of protecting the extremely immature lung from
      injury increasingly challenging. Premature infants at risk of developing chronic
      lung disease or bronchopulmonary dysplasia (BPD) are now born at the late
      canalicular stage of lung development, just when the airways become juxtaposed to
      the lung vasculature and when gas-exchange becomes possible. Readily available
      strategies, including improved antenatal management (education, regionalization,
      steroids, and antibiotics), together with exogenous surfactant and
      exclusive/early noninvasive ventilatory support, will likely decrease the
      incidence/severity of BPD over the next few years. Nonetheless, because of the
      extreme immaturity of the developing lung, the extent to which disruption of lung
      growth after prematurity and neonatal management lead to an earlier or more
      aggravated decline in respiratory function in later life is a matter of concern.
      Consequently, much more needs to be learned about the mechanisms of lung
      development, injury, and repair. Recent insight into stem cell biology has
      sparked interest for stem cells to repair damaged organs. This review summarizes
      the exciting potential of stem cell-based therapies for lung diseases in general
      and BPD in particular.

PMID- 22400814
TI  - Master equations for correlated quantum channels.
AB  - We derive the general form of a master equation describing the reduced time
      evolution of a sequence of subsystems "propagating" in an environment which can
      be described as a sequence of subenvironments. The interaction between subsystems
      and subenvironments is described in terms of a collision model, with the
      irreversible dynamics of the subenvironments between collisions explicitly taken
      into account. In the weak coupling regime, we show that the collisional model
      produces a correlated Markovian evolution for the joint density matrix of the
      multipartite system. The associated Lindblad superoperator contains pairwise
      terms describing cross correlation between the different subsystems. Such a model
      can describe a broad range of physical situations, ranging from quantum channels
      with memory to photon propagation in concatenated quantum optical systems.

PMID- 22400815
TI  - Nonlocality tests enhanced by a third observer.
AB  - We consider Bell tests involving bipartite states shared between three parties.
      We show that the simple inclusion of a third part may greatly simplify the
      measurement scenario (in terms of the number of measurement settings per part)
      and allows the identification of previously unknown nonlocal resources.

PMID- 22400816
TI  - When does noise increase the quantum capacity?
AB  - Superactivation is the property that two channels with zero quantum capacity can
      be used together to yield a positive capacity. Here we demonstrate that this
      effect exists for a wide class of inequivalent channels, none of which can
      simulate each other. We also consider the case where one of two zero-capacity
      channels is applied, but the sender is ignorant of which one is applied. We find
      examples where the greater the entropy of mixing of the channels, the greater the
      lower bound for the capacity. Finally, we show that the effect of superactivation
      is rather generic by providing an example of superactivation using the
      depolarizing channel.

PMID- 22400817
TI  - Benchmarking a quantum teleportation protocol in superconducting circuits using
      tomography and an entanglement witness.
AB  - Teleportation of a quantum state may be used for distributing entanglement
      between distant qubits in quantum communication and for quantum computation. Here
      we demonstrate the implementation of a teleportation protocol, up to the single
      shot measurement step, with superconducting qubits coupled to a microwave
      resonator. Using full quantum state tomography and evaluating an entanglement
      witness, we show that the protocol generates a genuine tripartite entangled state
      of all three qubits. Calculating the projection of the measured density matrix
      onto the basis states of two qubits allows us to reconstruct the teleported
      state. Repeating this procedure for a complete set of input states we find an
      average output state fidelity of 86%.

PMID- 22400818
TI  - Indistinguishable entangled photons generated by a light-emitting diode.
AB  - A linear optical quantum computer relies on interference between photonic qubits
      for logic, and entanglement for near-deterministic operation. Here we measure the
      interference and entanglement properties of photons emitted by a quantum dot
      embedded within a light-emitting diode. We show that pairs of simultaneously
      generated photons are entangled, and indistinguishable from subsequently
      generated photons. We measure entanglement fidelity of 0.87 and two-photon
      interference visibility of 0.60 +/- 0.05. The visibility, limited by detector
      jitter, could be improved by optical cavity designs.

PMID- 22400819
TI  - Quantum one-time pad in the presence of an eavesdropper.
AB  - A classical one-time pad allows two parties to send private messages over a
      public classical channel-an eavesdropper who intercepts the communication learns
      nothing about the message. A quantum one-time pad is a shared quantum state which
      allows two parties to send private messages or private quantum states over a
      public quantum channel. If the eavesdropper intercepts the quantum communication
      she learns nothing about the message. In the classical case, a one-time pad can
      be created using shared and partially private correlations. Here we consider the
      quantum case in the presence of an eavesdropper, and find the single-letter
      formula for the rate at which the two parties can send messages using a general
      quantum state as a quantum one-time pad. Surprisingly, the formula coincides with
      the distillable entanglement assisted by a symmetric channel, an important
      quantity in quantum information theory, but which lacked a clear operational
      meaning.

PMID- 22400820
TI  - Universal order statistics of random walks.
AB  - We study analytically the order statistics of a time series generated by the
      positions of a symmetric random walk of n steps with step lengths of finite
      variance sigma(2). We show that the statistics of the gap d(k,n) = M(k,n)
      M(k+1,n) between the kth and the (k+1)th maximum of the time series becomes
      stationary, i.e., independent of n as n -> infinity and exhibits a rich,
      universal behavior. The mean stationary gap exhibits a universal algebraic decay
      for large k, ~d(k,infinity)-/sigma 1/sqrt[2pik], independent of the details of
      the jump distribution. Moreover, the probability density (pdf) of the stationary
      gap exhibits scaling, Pr(d(k,infinity) = delta) ~/=
      (sqrt[k]/sigma)P(deltasqrt[k]/sigma), in the regime delta~ (d(k,infinity)). The
      scaling function P(x) is universal and has an unexpected power law tail, P(x) ~
      x(-4) for large x. For delta>> (d(k,infinity)) the scaling breaks down and the
      pdf gets cut off in a nonuniversal way. Consequently, the moments of the gap
      exhibit an unusual multiscaling behavior.

PMID- 22400821
TI  - Resolving the ghost problem in nonlinear massive gravity.
AB  - We analyze the ghost issue in the recently proposed models of nonlinear massive
      gravity in the Arnowitt-Deser-Misner formalism. We show that, in the entire two
      parameter family of actions, the Hamiltonian constraint is maintained at the
      complete nonlinear level and we argue for the existence of a nontrivial secondary
      constraint. This implies the absence of the pathological Boulware-Deser ghost to
      all orders. To our knowledge, this is the first demonstration of the existence of
      a consistent theory of massive gravity at the complete nonlinear level, in four
      dimensions.

PMID- 22400822
TI  - Temperature dependence of standard model CP violation.
AB  - We analyze the temperature dependence of CP violation effects in the standard
      model by determining the effective action of its bosonic fields, obtained after
      integrating out the fermions from the theory and performing a covariant gradient
      expansion. We find nonvanishing CP violating terms starting at the sixth order of
      the expansion, albeit only in the C-odd-P-even sector, with coefficients that
      depend on quark masses, Cabibbo-Kobayashi-Maskawa matrix elements, temperature
      and the magnitude of the Higgs field. The CP violating effects are observed to
      decrease rapidly with temperature, which has important implications for the
      generation of a matter-antimatter asymmetry in the early Universe. Our results
      suggest that the cold electroweak baryogenesis scenario may be viable within the
      standard model, provided the electroweak transition temperature is at most of
      order 1 GeV.

PMID- 22400823
TI  - Residual symmetries for neutrino mixing with a large theta13 and nearly maximal
      deltaD.
AB  - The residual Z(2)(s)(k) and Z(2)(s)(k) symmetries induce a direct and unique
      phenomenological relation with thetax (= theta13) expressed in terms of the other
      two mixing angles thetas(= theta12) and thetaa(= theta23) and the Dirac CP phase
      deltaD. Z(2)(s)(k) predicts a thetax probability distribution centered around 3
      degrees -6 degrees  with an uncertainty of 2 degrees -4 degrees , while those
      from Z(2)(s)(k) are approximately a factor of 2 larger. Either result fits the
      T2K, MINOS, and Double Chooz measurements. Alternately, a prediction for the
      Dirac CP phase deltaD results in a peak at +/- 74 degrees  (+/- 106 degrees ) for
      Z(2)(s)(k) or +/- 123 degrees  (+/- 57 degrees ) for Z(2)(s)(k) which is
      consistent with the latest global fit. We also give a distribution for the
      leptonic Jarlskog invariant Jnu which can provide further tests from measurements
      at T2K and NOnuA.

PMID- 22400824
TI  - Superconformal technicolor.
AB  - In supersymmetric theories with a strong conformal sector, soft supersymmetry
      breaking at the TeV scale naturally gives rise to confinement and chiral symmetry
      breaking at the same scale. We consider two such scenarios, one where the strong
      dynamics induces vacuum expectation values for elementary Higgs fields, and
      another where the strong dynamics is solely responsible for electroweak symmetry
      breaking. In both cases, the mass of the Higgs boson can exceed the LEP bound
      without tuning, solving the supersymmetry naturalness problem. A good precision
      electroweak fit can be obtained, and quark and lepton masses are generated
      without flavor-changing neutral currents. In addition to standard supersymmetry
      signals, these models predict production of multiple heavy standard model
      particles (t, W, Z, and b) from decays of resonances in the strong sector.

PMID- 22400825
TI  - Reweighing the evidence for a light Higgs boson in dileptonic W boson decays.
AB  - We reconsider observables for discovering and measuring the mass of a Higgs boson
      via its dileptonic decays h -> W W* -> lnulnu. We define an observable
      generalizing the transverse mass that takes into account the fact that one of the
      intermediate W bosons is likely to be on shell. We compare this new variable with
      existing ones and argue that it gives a significant improvement for discovery in
      the region mh < 2 mW.

PMID- 22400830
TI  - Ab initio many-body calculations of the (3)H(d,n)(4)He and (3)He(d,p)(4)He fusion
      reactions.
AB  - We apply the ab initio no-core shell model combined with the resonating-group
      method approach to calculate the cross sections of the (3)H(d,n)(4)He and
      (3)He(d,p)(4)He fusion reactions. These are important reactions for the big bang
      nucleosynthesis and the future of energy generation on Earth. Starting from a
      selected similarity-transformed chiral nucleon-nucleon interaction that
      accurately describes two-nucleon data, we performed many-body calculations that
      predict the S factor of both reactions. Virtual three-body breakup effects are
      obtained by including excited pseudostates of the deuteron in the calculation.
      Our results are in satisfactory agreement with experimental data and pave the way
      for microscopic investigations of polarization and electron-screening effects, of
      the (3)H(d,gamman)(4)He bremsstrahlung and other reactions relevant to fusion
      research.

PMID- 22400829
TI  - Photodisintegration cross section of the reaction (4)He(gamma,p)(3)H between 22
      and 30 MeV.
AB  - The two-body photodisintegration cross section of (4)He into a proton and triton
      was measured with monoenergetic photon beams in 0.5 MeV energy steps between 22
      and 30 MeV. High-pressure (4)He-Xe gas scintillators of various (4)He/Xe ratios
      served as targets and detectors. Pure Xe gas scintillators were used for
      background studies. A NaI detector together with a plastic scintillator paddle
      was employed for determining the incident photon flux. Our comprehensive data set
      follows the trend of the theoretical calculations of the Trento group very well,
      although our data are consistently lower in magnitude by about 5%. However, they
      differ significantly from the majority of the previous data, especially from the
      recent data of Shima et al. The latter data had put into question the validity of
      theoretical approaches used to calculate core-collapse supernova explosions and
      big-bang nucleosynthesis abundances of certain light nuclei.

PMID- 22400833
TI  - Creating and transporting Trojan wave packets.
AB  - Nondispersive localized Trojan wave packets with n(i) ~ 305 moving in near
      circular Bohr-like orbits are created and transported to localized near-circular
      Trojan states of higher n, n(f) ~ 600, by driving with a linearly polarized
      sinusoidal electric field whose period is slowly increased. The protocol is
      remarkably efficient with over 80% of the initial atoms being transferred to the
      higher n states, a result confirmed by classical trajectory Monte Carlo
      simulations.

PMID- 22400832
TI  - Symmetry restoration in Hartree-Fock-Bogoliubov based theories.
AB  - We present a Pfaffian formula for projection and symmetry restoration for wave
      functions of the general Bogoliubov form, including quasiparticle excited states
      and linear combinations of them. This solves a long-standing problem in
      calculating states of good symmetry, arising from the sign ambiguity of the
      commonly used determinant formula. A simple example is given of projecting a good
      particle number and angular momentum from a Bogoliubov wave function in the Fock
      space of a single j-shell.

PMID- 22400831
TI  - Nuclear charge radii of (21-32)Mg.
AB  - Charge radii of all magnesium isotopes in the sd shell have been measured,
      revealing evolution of the nuclear shape throughout two prominent regions of
      assumed deformation centered on (24)Mg and (32)Mg. A striking correspondence is
      found between the nuclear charge radius and the neutron shell structure. The
      importance of cluster configurations towards N=8 and collectivity near N=20 is
      discussed in the framework of the fermionic molecular dynamics model. These
      essential results have been made possible by the first application of laser
      induced nuclear orientation for isotope shift measurements.

PMID- 22400828
TI  - Evidence for heavy hyperhydrogen (Lambda)(6)h.
AB  - Evidence for the neutron-rich hypernucleus (Lambda)(6)H is presented from the
      FINUDA experiment at DAPhiNE, Frascati, studying (pi+,pi-) pairs in coincidence
      from the K(stop)(-) + (6)Li ->(Lambda)(6)H + pi+ production reaction followed by
      (Lambda)(6)H -> (6)He + pi- weak decay. The production rate of (Lambda)(6)
      undergoing this two-body pi- decay is determined to be (2.9 +/- 2.0) * 10(
      6)/K(stop)(-). Its binding energy, evaluated jointly from production and decay,
      is BLambda((Lambda)(6)H) = (4.0 +/- 1.1) MeV with respect to (5)H+Lambda. A
      systematic difference of (0.98 +/- 0.74) MeV between BLambda values derived
      separately from decay and from production is tentatively assigned to the
      (Lambda)(6)H 0(g.s.)(+) -> 1+ excitation.

PMID- 22400834
TI  - Coulomb asymmetry in strong field multielectron ionization of diatomic molecules.
AB  - We measure the angular distribution of an electron emitted by a strong
      elliptically polarized two-color laser field from exploding doubly charged
      molecular nitrogen. This angular distribution is vastly different for emission of
      the electron from the up-field core of the molecule as compared to that from the
      down-field core. The emission from the down-field core leads to a slight rotation
      with respect to the internuclear axis in the direction expected by the Coulomb
      effect of the remaining ion, while, for the emission from the up-field core, this
      direction is inversed. Our semiclassical simulations suggest that this unexpected
      angular distribution is caused by an initial longitudinal momentum of the
      electron freed by over-the-barrier ionization above the inner barrier in the
      molecule. The initial kinetic energy is in the range of the potential energy of
      the Stark-shifted orbital above the barrier.

PMID- 22400835
TI  - Nonequilibrium quantum phase transitions in the Dicke model.
AB  - We establish a set of nonequilibrium quantum phase transitions in the Dicke model
      by considering a monochromatic nonadiabatic modulation of the atom-field
      coupling. For weak driving the system exhibits a set of sidebands which allow the
      circumvention of the no-go theorem which otherwise forbids the occurrence of
      superradiant phase transitions. At strong driving we show that the system
      exhibits a rich multistable structure and exhibits both first- and second-order
      nonequilibrium quantum phase transitions.

PMID- 22400836
TI  - Molecular imaging using high-order harmonic generation and above-threshold
      ionization.
AB  - Accurate molecular imaging via high-order harmonic generation relies on comparing
      harmonic emission from a laser-irradiated molecule and an adequate reference
      system. However, an ideal reference atom with the same ionization properties as
      the molecule is not always available. We show that for suitably designed, very
      short laser pulses, a one-to-one mapping from high-order harmonic frequencies to
      electron momenta in above-threshold ionization exists. Comparing molecular and
      atomic momentum distributions then provides the electron recollision amplitude in
      the molecule for enhanced molecular imaging. The method retrieves the molecular
      recombination transition moments highly accurately, even with suboptimal
      reference atoms.

PMID- 22400837
TI  - Enhancement of blackbody friction due to the finite lifetime of atomic levels.
AB  - The thermal friction force acting on an atom moving relative to a thermal photon
      bath is known to be proportional to an integral over the imaginary part of the
      frequency-dependent atomic (dipole) polarizability. Using a numerical approach,
      we find that blackbody friction on atoms either in dilute environments or in hot
      ovens is larger than previously thought by orders of magnitude. This enhancement
      is due to far off-resonant driving of transitions by low-frequency thermal
      radiation. At typical temperatures, the blackbody radiation maximum lies far
      below the atomic transition wavelengths. Surprisingly, due to the finite lifetime
      of atomic levels, which gives rise to Lorentzian line profiles, far off-resonant
      excitation leads to the dominant contribution for blackbody friction.

PMID- 22400838
TI  - Magnetically tunable Feshbach resonances in ultracold Li-Yb mixtures.
AB  - We investigate the possibility of forming Li+Yb ultracold molecules by
      magnetoassociation in mixtures of ultracold atoms. We find that magnetically
      tunable Feshbach resonances exist, but are extremely narrow for even-mass
      ytterbium isotopes, which all have zero spin. For odd-mass Yb isotopes, however,
      there is a new mechanism due to hyperfine coupling between the electron spin and
      the Yb nuclear magnetic moment. This mechanism produces Feshbach resonances for
      fermionic Yb isotopes that can be more than 2 orders of magnitude larger than for
      the bosonic counterparts.

PMID- 22400839
TI  - Strongly enhanced backward emission of electrons in transfer and ionization.
AB  - We studied three-dimensional angular distributions and longitudinal momentum
      spectra of electrons ejected in transfer plus ionization (TI), i.e., the ejection
      of one and the capture of a second target electron, for ion-helium collisions. We
      observe a pronounced structure strongly focused opposite to the projectile beam
      direction, which we associate with a new correlated TI mechanism proposed
      recently. This process contributes significantly to the total cross sections over
      a broad range of perturbations eta, even at eta as large as 0.5, where
      uncorrelated TI mechanisms were thought to be dominant.

PMID- 22400840
TI  - Efficient production of Rydberg positronium.
AB  - We demonstrate experimentally the production of Rydberg positronium (Ps) atoms in
      a two-step process, comprising incoherent laser excitation, first to the 2(3)P
      state and then to states with principal quantum numbers ranging from 10 to 25. We
      find that excitation of 2(3)P atoms to Rydberg levels occurs very efficiently
      (~90%) and that the ~25% overall efficiency of the production of Rydberg atoms is
      determined almost entirely by the spectral overlap of the primary excitation
      laser and the Doppler broadened width of the 1 (3)S-2(3)P transition. The
      observed efficiency of Rydberg Ps production can be explained if stimulated
      emission back to the 2P states is suppressed, for example, by intermixing of the
      Rydberg state Stark sublevels. The efficient production of long-lived Rydberg Ps
      in a high magnetic field may make it possible to perform direct measurements of
      the gravitational free fall of Ps.

PMID- 22400841
TI  - Correlated photon emission from multiatom Rydberg dark States.
AB  - We consider three-level atoms driven by two resonant light fields in a ladder
      scheme where the upper level is a highly excited Rydberg state. We show that the
      dipole-dipole interactions between Rydberg excited atoms prevents the formation
      of single particle dark states and leads to strongly correlated photon pairs from
      atoms separated by distances large compared to the emission wavelength. For a
      pair of atoms, this enables realization of an efficient photon-pair source with
      on average one pair every 30 MUs.

PMID- 22400842
TI  - Shaping an itinerant quantum field into a multimode squeezed vacuum by
      dissipation.
AB  - We show that inducing sidebands in the emission of a single emitter into a one
      dimensional waveguide, together with a dissipative repumping process, a photon
      field is cooled down to a multimode squeezed vacuum. Our method does not require
      being in the strong coupling regime, works with a continuum of propagating field
      modes, and leads to sources of tunable multimode squeezed light in circuit-QED
      systems.

PMID- 22400843
TI  - Direct observation of non-Markovian radiation dynamics in 3D bulk photonic
      crystals.
AB  - Since the very first proposition of photonic crystals, their influence on the
      dynamics of spontaneous emission has been of great interest. The radiation
      dynamics is described by an integration kernel which--in a spectral
      representation--comprises two equally important contributions: the Lamb shift and
      the radiative contribution to the linewidth. The latter is connected to the
      density of states via Fermi's golden rule. To our knowledge, we present the first
      spatially resolved measurement of the complete radiation dynamics in a photonic
      crystal and of its local density of states over a wide spectral range. To this
      end we study a single magnetic dipole situated in a photonic crystal with a band
      gap at microwave frequencies and find non-Markovian behavior in excellent
      agreement with ab initio calculations.

PMID- 22400844
TI  - Two-photon quantum interference from separate nitrogen vacancy centers in
      diamond.
AB  - We report on the observation of quantum interference of the emission from two
      separate nitrogen vacancy (NV) centers in diamond. Taking advantage of optically
      induced spin polarization in combination with polarization filtering, we isolate
      a single transition within the zero-phonon line of the nonresonantly excited NV
      centers. The time-resolved two-photon interference contrast of this filtered
      emission reaches 66%. Furthermore, we observe quantum interference from
      dissimilar NV centers tuned into resonance through the dc Stark effect. These
      results pave the way towards measurement-based entanglement between remote NV
      centers and the realization of quantum networks with solid-state spins.

PMID- 22400845
TI  - Transmission eigenvalues and the bare conductance in the crossover to Anderson
      localization.
AB  - We measure the field transmission matrix t for microwave radiation propagating
      through random waveguides in the crossover to Anderson localization. From these
      measurements, we determine the dimensionless conductance g and the individual
      eigenvalues tau(n) of the transmission matrix tt(?) whose sum equals g. In
      diffusive samples, the highest eigenvalue, tau(1), is close to unity
      corresponding to a transmission of nearly 100%, while for localized waves, the
      average of tau(1), is nearly equal to g. We find that the spacing between average
      values of lntau(n) is constant and demonstrate that when surface interactions are
      taken into account it is equal to the inverse of the bare conductance.

PMID- 22400846
TI  - Loss of phase of collapsing beams.
AB  - We experimentally investigate the phase of an optical field after it has
      undergone wave collapse. We confirm the theoretical prediction that it acquires a
      large cumulative nonlinear phase shift that is highly sensitive to small
      fluctuations of the laser input power. This results in an effective postcollapse
      "loss of phase," whereby the phase of the transmitted beam shows a significant
      increase in sensitivity to the input fluctuations of the pulse energy. We also
      investigate interactions between two beams that each undergoes collapse and
      observe large fluctuations in the output mode profiles, which are due to the
      postcollapse loss of their relative phase difference. Such effects should occur
      in all systems that exhibit wave collapse.

PMID- 22400847
TI  - Self-sustained localized structures in a boundary-layer flow.
AB  - When a boundary layer starts to develop spatially over a flat plate, only
      disturbances of sufficiently large amplitude survive and trigger turbulence
      subcritically. Direct numerical simulation of the Blasius boundary-layer flow is
      carried out to track the dynamics in the region of phase space separating
      transitional from relaminarizing trajectories. In this intermediate regime, the
      corresponding disturbance is fully localized and spreads slowly in space. This
      structure is dominated by a robust pair of low-speed streaks, whose convective
      instabilities spawn hairpin vortices evolving downstream into transient
      disturbances. A quasicyclic mechanism for the generation of offspring is unfolded
      using dynamical rescaling with the local boundary-layer thickness.

PMID- 22400848
TI  - Shock modon: a new type of coherent structure in rotating shallow water.
AB  - We show that a new type of coherent structure, a shock modon, exists in a
      rotating shallow water model at large Rossby numbers. It is a combination of an
      asymmetric vortex dipole with a stationary hydraulic jump. The structure is long
      living, despite the energy dissipation by the hydraulic jump, and moving along a
      circular path. Collisions of shock modons can be elastic, or lead to formation of
      shock tripoles.

PMID- 22400849
TI  - Flame speed and self-similar propagation of expanding turbulent premixed flames.
AB  - In this Letter we present turbulent flame speeds and their scaling from
      experimental measurements on constant-pressure, unity Lewis number expanding
      turbulent flames, propagating in nearly homogeneous isotropic turbulence in a
      dual-chamber, fan-stirred vessel. It is found that the normalized turbulent flame
      speed as a function of the average radius scales as a turbulent Reynolds number
      to the one-half power, where the average radius is the length scale and the
      thermal diffusivity is the transport property, thus showing self-similar
      propagation. Utilizing this dependence it is found that the turbulent flame
      speeds from the present expanding flames and those from the Bunsen geometry in
      the literature can be unified by a turbulent Reynolds number based on flame
      length scales using recent theoretical results obtained by spectral closure of
      the transformed G equation.

PMID- 22400850
TI  - Spin-to-orbital angular momentum conversion and spin-polarization filtering in
      electron beams.
AB  - We propose the design of a space-variant Wien filter for electron beams that
      induces a spin half-turn and converts the corresponding spin angular momentum
      variation into orbital angular momentum of the beam itself by exploiting a
      geometrical phase arising in the spin manipulation. When applied to a spatially
      coherent input spin-polarized electron beam, such a device can generate an
      electron vortex beam, carrying orbital angular momentum. When applied to an
      unpolarized input beam, the proposed device, in combination with a suitable
      diffraction element, can act as a very effective spin-polarization filter. The
      same approach can also be applied to neutron or atom beams.

PMID- 22400851
TI  - Local kinetic effects in two-dimensional plasma turbulence.
AB  - Using direct numerical simulations of a hybrid Vlasov-Maxwell model, kinetic
      processes are investigated in a two-dimensional turbulent plasma. In the
      turbulent regime, kinetic effects manifest through a deformation of the ion
      distribution function. These patterns of non-Maxwellian features are concentrated
      in space nearby regions of strong magnetic activity: the distribution function is
      modulated by the magnetic topology, and can elongate along or across the local
      magnetic field. These results open a new path on the study of kinetic processes
      such as heating, particle acceleration, and temperature anisotropy, commonly
      observed in astrophysical and laboratory plasmas.

PMID- 22400852
TI  - Construction of analytical many-body wave functions for correlated bosons in a
      harmonic trap.
AB  - We develop an analytical many-body wave function to accurately describe the
      crossover of a one-dimensional bosonic system from weak to strong interactions in
      a harmonic trap. The explicit wave function, which is based on the exact two-body
      states, consists of symmetric multiple products of the corresponding parabolic
      cylinder functions and respects the analytically known limits of zero and
      infinite repulsion for arbitrary number of particles. For intermediate
      interaction strengths we demonstrate that the energies, as well as the reduced
      densities of first and second order, are in excellent agreement with large scale
      numerical calculations.

PMID- 22400853
TI  - Evolution of fermion pairing from three to two dimensions.
AB  - We follow the evolution of fermion pairing in the dimensional crossover from
      three-dimensional to two-dimensional as a strongly interacting Fermi gas of
      ^{6}Li atoms becomes confined to a stack of two-dimensional layers formed by a
      one-dimensional optical lattice. Decreasing the dimensionality leads to the
      opening of a gap in radio-frequency spectra, even on the Bardeen-Cooper
      Schrieffer side of a Feshbach resonance. The measured binding energy of fermion
      pairs closely follows the theoretical two-body binding energy and, in the two
      dimensional limit, the zero-temperature mean-field Bose-Einstein-condensation to
      Bardeen-Cooper-Schrieffer crossover theory.

PMID- 22400854
TI  - Universal mechanism of dissipation in Fermi superfluids at ultralow temperatures.
AB  - We show that the vortex dynamics in Fermi superfluids at ultralow temperatures is
      governed by the local heating of the vortex cores creating the heat flux carried
      by nonequilibrium quasiparticles emitted by moving vortices. This mechanism
      provides a universal zero temperature limit of dissipation in Fermi superfluids.
      For the typical experimental conditions realized by the turbulent motion of
      ^{3}He-B, the temperature of the vortex cores is estimated to be of the order 0.2
      T(c). The dispersion of Kelvin waves is derived, and the heat flow generated by
      Kelvin cascade is shown to have a value close to that experimentally observed.

PMID- 22400855
TI  - Realization of a resonant Fermi gas with a large effective range.
AB  - We have measured the interaction energy and three-body recombination rate for a
      two-component Fermi gas near a narrow Feshbach resonance and found both to be
      strongly energy dependent. Even for de Broglie wavelengths greatly exceeding the
      van der Waals length scale, the behavior of the interaction energy as a function
      of temperature cannot be described by atoms interacting via a contact potential.
      Rather, energy-dependent corrections beyond the scattering length approximation
      are required, indicating a resonance with an anomalously large effective range.
      For fields where the molecular state is above threshold, the rate of three-body
      recombination is enhanced by a sharp, two-body resonance arising from the closed
      channel molecular state which can be magnetically tuned through the continuum.
      This narrow resonance can be used to study strongly correlated Fermi gases that
      simultaneously have a sizable effective range and a large scattering length.

PMID- 22400856
TI  - Ultracold atoms in a tunable optical kagome lattice.
AB  - We realize a two-dimensional kagome lattice for ultracold atoms by overlaying two
      commensurate triangular optical lattices generated by light at the wavelengths of
      532 and 1064 nm. Stabilizing and tuning the relative position of the two
      lattices, we explore different lattice geometries including a kagome, a one
      dimensional stripe, and a decorated triangular lattice. We characterize these
      geometries using Kapitza-Dirac diffraction and by analyzing the Bloch-state
      composition of a superfluid released suddenly from the lattice. The Bloch-state
      analysis also allows us to determine the ground-state distribution within the
      superlattice unit cell. The lattices implemented in this work offer a near-ideal
      realization of a paradigmatic model of many-body quantum physics, which can serve
      as a platform for future studies of geometric frustration.

PMID- 22400857
TI  - Correlated phases of bosons in the flat lowest band of the dice lattice.
AB  - We study correlated phases occurring in the flat lowest band of the dice-lattice
      model at flux density one-half. We discuss how to realize this model, also
      referred to as the T(3) lattice, in cold atomic gases. We construct the
      projection of the model to the lowest dice band, which yields a Hubbard
      Hamiltonian with interaction-assisted hopping processes. We solve this model for
      bosons in two limits. In the limit of large density, we use Gross-Pitaevskii mean
      field theory to reveal time-reversal symmetry breaking vortex lattice phases. At
      low density, we use exact diagonalization to identify three stable phases at
      fractional filling factors nu of the lowest band, including a classical crystal
      at nu = 1/3, a supersolid state at nu = 1/2, and a Mott insulator at nu = 1.

PMID- 22400858
TI  - Thermodynamics of a Bose-Einstein condensate with free magnetization.
AB  - We study thermodynamic properties of a gas of spin 3(52)Cr atoms across Bose
      Einstein condensation. Magnetization is free, due to dipole-dipole interactions.
      We show that the critical temperature for condensation is lowered at extremely
      low magnetic fields, when the spin degree of freedom is thermally activated. The
      depolarized gas condenses in only one spin component, unless the magnetic field
      is set below a critical value, below which a nonferromagnetic phase is favored.
      Finally, we present a spin thermometry efficient even below the degeneracy
      temperature.

PMID- 22400859
TI  - Onset temperature of Bose-Einstein condensation in incommensurate solid (4)He.
AB  - The temperature dependence of the one-body density matrix in (4)He crystals
      presenting vacancies is computed with path integral Monte Carlo simulations. The
      main purpose of this study is to estimate the onset temperature T(0) of Bose
      Einstein condensation in these systems. We see that T(0) depends on the vacancy
      concentration X(v) of the simulated system, but not following the law T(0) ~
      X(v)(2/3) obtained assuming noninteracting vacancies. For the lowest X(v) we
      study, that is X(v)= 1/256, we get T(0) = 0.15 +/- 0.05 K, close to the
      temperatures at which a finite fraction of nonclassical rotational inertia is
      experimentally observed. Below T(0), vacancies do not act as classical point
      defects becoming completely delocalized entities.

PMID- 22400860
TI  - Nonadiabatic study of dynamic electronic effects during brittle fracture of
      silicon.
AB  - It has long been observed that brittle fracture of materials can lead to emission
      of high energy electrons and UV photons, but an atomistic description of the
      origin of such processes has lacked. We report here on simulations using a first
      principles-based electron force field methodology with effective core potentials
      to describe the nonadiabatic quantum dynamics during brittle fracture in silicon
      crystal. Our simulations replicate the correct response of the crack tip velocity
      to the threshold critical energy release rate, a feat that is inaccessible to
      quantum mechanics methods or conventional force-field-based molecular dynamics.
      We also describe the crack induced voltages, current bursts, and charge carrier
      production observed experimentally during fracture but not previously captured in
      simulations. We find that strain-induced surface rearrangements and local heating
      cause ionization of electrons at the fracture surfaces.

PMID- 22400861
TI  - Lattice dynamics and superconductivity in cerium at high pressure.
AB  - We have measured phonon dispersion relations of the high-pressure phase cerium
      oC4 (alpha' phase with the alpha-uranium crystal structure) at 6.5 GPa by using
      inelastic x-ray scattering. Pronounced phonon anomalies are observed, which are
      remarkably similar to those of alpha-U. First-principles electronic structure
      calculations reproduce the anomalies and allow us to identify strong electron
      phonon coupling as their origin. At the low-pressure end of its stability range,
      Ce-oC4 is on the verge of a lattice-dynamical instability and possibly a charge
      density wave. The superconducting transition temperatures of the fcc, oC4, and
      mC4 phases of Ce have been calculated, and the superconductivity observed
      experimentally by Wittig and Probst is attributed to the oC4 phase.

PMID- 22400862
TI  - Persistence and eventual demise of oxygen molecules at terapascal pressures.
AB  - Computational searches for structures of solid oxygen under high pressures in the
      multi-TPa range are carried out using density-functional-theory methods. We find
      that molecular oxygen persists to about 1.9 TPa at which it transforms into a
      semiconducting square-spiral-like polymeric structure (I4(1)/acd) with a band gap
      of ~3.0 eV. Solid oxygen forms a metallic zigzag chainlike structure (Cmcm) at
      about 3.0 TPa, but the chains in each layer gradually merge as the pressure is
      increased and a structure of Fmmm symmetry forms at about 9.3 TPa in which each
      atom has four nearest neighbors. The superconducting properties of molecular
      oxygen do not vary much with compression, although the structure becomes more
      symmetric. The electronic properties of oxygen have a complex evolution with
      pressure, swapping between insulating, semiconducting, and metallic.

PMID- 22400863
TI  - Hierarchical freezing in a lattice model.
AB  - A certain two-dimensional lattice model with nearest and next-nearest neighbor
      interactions is known to have a limit-periodic ground state. We show that during
      a slow quench from the high temperature, disordered phase, the ground state
      emerges through an infinite sequence of phase transitions. We define appropriate
      order parameters and show that the transitions are related by renormalizations of
      the temperature scale. As the temperature is decreased, sublattices with
      increasingly large lattice constants become ordered. A rapid quench results in a
      glasslike state due to kinetic barriers created by simultaneous freezing on
      sublattices with different lattice constants.

PMID- 22400864
TI  - Ashkin-teller criticality and pseudo-first-order behavior in a frustrated Ising
      model on the square lattice.
AB  - We study the challenging thermal phase transition to stripe order in the
      frustrated square-lattice Ising model with couplings J(1) < 0 (nearest-neighbor,
      ferromagnetic) and J(2) > 0 (second-neighbor, antiferromagnetic) for g =
      J(2)/|J(1| > 1/2. Using Monte Carlo simulations and known analytical results, we
      demonstrate Ashkin-Teller criticality for g >= g*; i.e., the critical exponents
      vary continuously between those of the 4-state Potts model at g = g* and the
      Ising model for g -> infinity. Thus, stripe transitions offer a route to
      realizing a related class of conformal field theories with conformal charge c = 1
      and varying exponents. The transition is first order for g < g* = 0.67 +/- 0.01,
      much lower than previously believed, and exhibits pseudo-first-order behavior for
      |g* <= g </~1.

PMID- 22400865
TI  - Retention capacity of random surfaces.
AB  - We introduce a "water retention" model for liquids captured on a random surface
      with open boundaries and investigate the model for both continuous and discrete
      surface heights 0,1,...,n-1 on a square lattice with a square boundary. The model
      is found to have several intriguing features, including a nonmonotonic dependence
      of the retention on the number of levels: for many n, the retention is
      counterintuitively greater than that of an (n+1)-level system. The behavior is
      explained using percolation theory, by mapping it to a 2-level system with
      variable probability. Results in one dimension are also found.

PMID- 22400866
TI  - Thermodynamically stable phases of carbon at multiterapascal pressures.
AB  - Phases of carbon are studied up to pressures of 1 petapascal (PPa) using first
      principles density-functional-theory methods and a structure searching algorithm.
      Our extensive search over the potential energy surface supports the sequence of
      transitions diamond -> BC8 -> simple cubic under increasing pressure found in
      previous theoretical studies. At higher pressures we predict a soft-phonon driven
      transition to a simple hexagonal structure at 6.4 terapascals (TPa), and further
      transitions to the face centered cubic electride structure at 21 TPa, a double
      hexagonal close packed structure at 270 TPa, and the body centered cubic
      structure at 650 TPa.

PMID- 22400867
TI  - Diffusion-induced oscillations of extended defects.
AB  - From a simple model for the driven motion of a planar interface under the
      influence of a diffusion field we derive a damped nonlinear oscillator equation
      for the interface position. Inside an unstable regime, where the damping term is
      negative, we find limit-cycle solutions, describing an oscillatory propagation of
      the interface. In the case of a growing solidification front this offers a
      transparent scenario for the formation of solute bands in binary alloys and,
      taking into account the Mullins-Sekerka instability, of banded structures.

PMID- 22400868
TI  - Topological order and semions in a strongly correlated quantum spin Hall
      insulator.
AB  - We provide a self-consistent mean-field framework to study the effect of strong
      interactions in a quantum spin Hall insulator on the honeycomb lattice. We
      identify an exotic phase for large spin-orbit coupling and intermediate Hubbard
      interaction. This phase is gapped and does not break any symmetry. Instead, we
      find a fourfold topological degeneracy of the ground state on the torus and
      fractionalized excitations with semionic mutual braiding statistics. Moreover, we
      argue that it has gapless edge modes protected by time-reversal symmetry but a
      trivial Z(2) topological invariant. Finally, we discuss the experimental
      signatures of this exotic phase. Our work highlights the important theme that
      interesting phases arise in the regime of strong spin-orbit coupling and
      interactions.

PMID- 22400869
TI  - Transverse conductivity in the sliding charge-density-wave state of NbSe3.
AB  - The dynamical properties of longitudinal and transverse conduction of NbSe3
      single crystals have been simultaneously studied when the current is applied
      along the b axis (chain direction). In the vicinity of the threshold electric
      field for charge-density-wave sliding, the transverse conduction sharply
      decreases. When a rf field is applied, voltage Shapiro steps for longitudinal
      transport are observed as usual but also current Shapiro steps in the transverse
      direction. The possible mechanisms of this effect are discussed.

PMID- 22400870
TI  - Enhancement of the Kondo effect through Rashba spin-orbit interactions.
AB  - We study a one-orbital Anderson impurity in a two-dimensional electron bath with
      Rashba spin-orbit interactions in the Kondo regime. The spin SU(2) symmetry
      breaking term couples the impurity to a two-band electron gas. A Schrieffer-Wolff
      transformation shows the existence of the Dzyaloshinsky-Moriya interaction away
      from the particle-hole symmetric impurity state. A renormalization group analysis
      reveals a two-channel Kondo model with ferro- and antiferromagnetic couplings.
      The parity-breaking Dzyaloshinsky-Moriya term renormalizes the antiferromagnetic
      Kondo coupling with an exponential enhancement of the Kondo temperature.

PMID- 22400871
TI  - Charge transport in Weyl semimetals.
AB  - We study transport in Weyl semimetals with N isotropic Weyl nodes in the presence
      of Coulomb interactions or disorder at temperature T. In the interacting clean
      limit, we determine the conductivity sigma(omega,T) by solving a quantum
      Boltzmann equation within a "leading log" approximation and find it to be
      proportional to T, up to logarithmic factors arising from the flow of couplings.
      In the noninteracting disordered case, we compute the Kubo conductivity and show
      that it behaves differently for omega << T and omega >> T: in the former regime
      we recover a previous result, of a finite dc conductivity and a Drude width
      vanishing as NT(2); in the latter, we find that sigma(omega,T) vanishes linearly
      with omega with a leading term as T -> 0 equal to the clean, free-fermion result:
      sigma(0)((N))(omega,T = 0) = Ne(2)/12h|omega|/v(F). We compare our results to
      transport data on Y(2)Ir(2)O(7) and comment on the possible relevance to recent
      experiments on Eu(2)Ir(2)O(7).

PMID- 22400872
TI  - Wave-function mapping of graphene quantum dots with soft confinement.
AB  - Using low-temperature scanning tunneling spectroscopy, we map the local density
      of states of graphene quantum dots supported on Ir(111). Because of a band gap in
      the projected Ir band structure around the graphene K point, the electronic
      properties of the QDs are dominantly graphenelike. Indeed, we compare the results
      favorably with tight binding calculations on the honeycomb lattice based on
      parameters derived from density functional theory. We find that the interaction
      with the substrate near the edge of the island gradually opens a gap in the Dirac
      cone, which implies soft-wall confinement. Interestingly, this confinement
      results in highly symmetric wave functions. Further influences of the substrate
      are given by the known moire potential and a 10% penetration of an Ir surface
      resonance into the graphene layer.

PMID- 22400873
TI  - Measurement of quantum noise in a carbon nanotube quantum dot in the Kondo
      regime.
AB  - The current emission noise of a carbon nanotube quantum dot in the Kondo regime
      is measured at frequencies nu of the order or higher than the frequency
      associated with the Kondo effect k(B)T (K)/h, with TK the Kondo temperature. The
      carbon nanotube is coupled via an on-chip resonant circuit to a quantum noise
      detector, a superconductor-insulator-superconductor junction. We find for hnu ~
      k(B)T(K) a Kondo effect related singularity at a voltage bias eV ~ hnu, and a
      strong reduction of this singularity for hnu ~ 3k(B)T(K), in good agreement with
      theory. Our experiment constitutes a new original tool for the investigation of
      the nonequilibrium dynamics of many-body phenomena in nanoscale devices.

PMID- 22400874
TI  - Magnetic-field probing of an SU(4) Kondo resonance in a single-atom transistor.
AB  - Semiconductor devices have been scaled to the point that transport can be
      dominated by only a single dopant atom. As a result, in a Si fin-type field
      effect transistor Kondo physics can govern transport when one electron is bound
      to the single dopant. Orbital (valley) degrees of freedom, apart from the
      standard spin, strongly modify the Kondo effect in such systems. Owing to the
      small size and the s-like orbital symmetry of the ground state of the dopant,
      these orbital degrees of freedom do not couple to external magnetic fields which
      allows us to tune the symmetry of the Kondo effect. Here we study this tunable
      Kondo effect and demonstrate experimentally a symmetry crossover from an SU(4)
      ground state to a pure orbital SU(2) ground state as a function of magnetic
      field. Our claim is supported by theoretical calculations that unambiguously show
      that the SU(2) symmetric case corresponds to a pure valley Kondo effect of fully
      polarized electrons.

PMID- 22400875
TI  - Quantized nu = 5/2 state in a two-subband quantum hall system.
AB  - The evolution of the fractional quantum Hall state at filling 5/2 is studied in
      density tunable two-dimensional electron systems formed in wide wells in which it
      is possible to induce a transition from single- to two-subband occupancy. In 80
      and 60 nm wells, the quantum Hall state at 5/2 filling of the lowest subband is
      observed even when the second subband is occupied. In a 50 nm well, the 5/2 state
      vanishes upon second subband population. We attribute this distinct behavior to
      the width dependence of the capacitive energy for intersubband charge transfer
      and of the overlap of the subband probability densities.

PMID- 22400876
TI  - Chiral orbital-angular momentum in the surface states of Bi2Se3.
AB  - We performed angle-resolved photoemission (ARPES) experiments with circularly
      polarized light and first-principles density functional calculation with spin
      orbit coupling to study surface states of a topological insulator Bi2Se3. We
      observed circular dichroism (CD) as large as 30% in the ARPES data with upper and
      lower Dirac cones showing opposite signs in CD. The observed CD is attributed to
      the existence of local orbital-angular momentum (OAM). First-principles
      calculation shows that OAM in the surface states is significant and is locked to
      the electron momentum in the opposite direction to the spin, forming chiral OAM
      states. Our finding opens a new possibility for strong light-induced spin
      polarized current in surface states. We also provide a proof for local OAM origin
      of the CD in ARPES.

PMID- 22400877
TI  - Topological Hubbard model and its high-temperature quantum Hall effect.
AB  - The quintessential two-dimensional lattice model that describes the competition
      between the kinetic energy of electrons and their short-range repulsive
      interactions is the repulsive Hubbard model. We study a time-reversal symmetric
      variant of the repulsive Hubbard model defined on a planar lattice: Whereas the
      interaction is unchanged, any fully occupied band supports a quantized spin Hall
      effect. We show that at 1/2 filling of this band, the ground state develops
      spontaneously and simultaneously Ising ferromagnetic long-range order and a
      quantized charge Hall effect when the interaction is sufficiently strong. We
      ponder on the possible practical applications, beyond metrology, that the
      quantized charge Hall effect might have if it could be realized at high
      temperatures and without external magnetic fields in strongly correlated
      materials.

PMID- 22400878
TI  - Dipole coupling of a double quantum dot to a microwave resonator.
AB  - We demonstrate the realization of a hybrid solid-state quantum device, in which a
      semiconductor double quantum dot is dipole coupled to the microwave field of a
      superconducting coplanar waveguide resonator. The double dot charge stability
      diagram extracted from measurements of the amplitude and phase of a microwave
      tone transmitted through the resonator is in good agreement with that obtained
      from transport measurements. Both the observed frequency shift and linewidth
      broadening of the resonator are explained considering the double dot as a charge
      qubit coupled with a strength of several tens of MHz to the resonator.

PMID- 22400879
TI  - Single-shot measurement of triplet-singlet relaxation in a Si/SiGe double quantum
      dot.
AB  - We investigate the lifetime of two-electron spin states in a few-electron Si/SiGe
      double dot. At the transition between the (1,1) and (0,2) charge occupations,
      Pauli spin blockade provides a readout mechanism for the spin state. We use the
      statistics of repeated single-shot measurements to extract the lifetimes of
      multiple states simultaneously. When the magnetic field is zero, we find that all
      three triplet states have equal lifetimes, as expected, and this time is ~10 ms.
      When the field is nonzero, the T(0) lifetime is unchanged, whereas the T-
      lifetime increases monotonically with the field, reaching 3 sec at 1 T.

PMID- 22400880
TI  - Antiferromagnetic spin fluctuations above the dome-shaped and full-gap
      superconducting states of LaFeAsO1-xFx revealed by (75)As-nuclear quadrupole
      resonance.
AB  - We report a systematic study by (75)As nuclear-quadrupole resonance in LaFeAsO(1
      x)F(x). The antiferromagnetic spin fluctuation found above the magnetic ordering
      temperature T(N) = 58 K for x = 0.03 persists in the regime 0.04 <= x <= 0.08,
      where superconductivity sets in. A dome-shaped x dependence of the
      superconducting transition temperature T(c) is found, with the highest T(c) = 27
      K at x = 0.06, which is realized under significant antiferromagnetic spin
      fluctuation. With increasing x further, the antiferromagnetic spin fluctuation
      decreases, and so does T(c). These features resemble closely the cuprates La(2
      x)Sr(x)CuO(4). In x = 0.06, the spin-lattice relaxation rate (1/T(1)) below T(c)
      decreases exponentially down to 0.13T(c), which unambiguously indicates that the
      energy gaps are fully opened. The temperature variation of 1/T(1) below T(c) is
      rendered nonexponential for other x by impurity scattering.

PMID- 22400881
TI  - de Haas-van Alphen study of the Fermi surfaces of superconducting LiFeP and
      LiFeAs.
AB  - We report a de Haas-van Alphen oscillation study of the 111 iron pnictide
      superconductors LiFeAs with T(c) ~ 18 K and LiFeP with T(c) ~ 5 K. We find that
      for both compounds the Fermi surface topology is in good agreement with density
      functional band-structure calculations and has almost nested electron and hole
      bands. The effective masses generally show significant enhancement, up to ~3 for
      LiFeP and ~5 for LiFeAs. However, one hole Fermi surface in LiFeP shows a very
      small enhancement, as compared with its other sheets. This difference probably
      results from k-dependent coupling to spin fluctuations and may be the origin of
      the different nodal and nodeless superconducting gap structures in LiFeP and
      LiFeAs, respectively.

PMID- 22400882
TI  - Nodal versus nodeless behaviors of the order parameters of LiFeP and LiFeAs
      superconductors from magnetic penetration-depth measurements.
AB  - High-precision measurements of magnetic penetration depth lambda in clean single
      crystals of LiFeAs and LiFeP superconductors reveal contrasting behaviors. In
      LiFeAs the low-temperature lambda(T) shows a flat dependence indicative of a
      fully gapped state, which is consistent with previous studies. In contrast, LiFeP
      exhibits a T-linear dependence of superfluid density infinity lambda(-2),
      indicating a nodal superconducting order parameter. A systematic comparison of
      quasiparticle excitations in the 1111, 122, and 111 families of iron-pnictide
      superconductors implies that the nodal state is induced when the pnictogen height
      from the iron plane decreases below a threshold value of ~1.33 A.

PMID- 22400883
TI  - Measurement of a pauli and orbital paramagnetic state in bulk gold using x-ray
      magnetic circular dichroism spectroscopy.
AB  - We show that bulk gold (Au) exhibits temperature-independent paramagnetism in an
      external magnetic field by x-ray magnetic circular dichroism spectroscopy at the
      Au L(2) and L(3) edges. Using the sum-rule analysis, we obtained a magnetic
      moment of 1.3 * 10(-4) MUB/atom in an external magnetic field of 10 T and a
      paramagnetic susceptibility of 8.9 * 10(-6) for the 5d orbit. The induced
      paramagnetism in bulk Au is characterized by a large (~ 30%) orbital
      contribution. This orbital component was retained even when Au atoms formed
      nanoparticles, playing an important role in stabilizing the spontaneous spin
      polarization in the Au nanoparticles.

PMID- 22400884
TI  - Topological quantum liquids with quaternion non-Abelian statistics.
AB  - Noncollinear magnetic order is typically characterized by a tetrad ground state
      manifold (GSM) of three perpendicular vectors or nematic directors. We study
      three types of tetrad orders in two spatial dimensions, whose GSMs are SO(3) =
      S(3)/Z(2), S(3)/Z(4), and S(3)/Q(8), respectively. Q(8) denotes the non-Abelian
      quaternion group with eight elements. We demonstrate that after quantum
      disordering these three types of tetrad orders, the systems enter fully gapped
      liquid phases described by Z(2), Z(4), and non-Abelian quaternion gauge field
      theories, respectively. The latter case realizes Kitaev's non-Abelian toric code
      in terms of a rather simple spin-1 SU(2) quantum magnet. This non-Abelian
      topological phase possesses a 22-fold ground state degeneracy on the torus
      arising from the 22 representations of the Drinfeld double of Q(8).

PMID- 22400885
TI  - Origin of the large polarization in multiferroic YMnO3 thin films revealed by
      soft- and hard-X-ray diffraction.
AB  - We investigated the magnetic structure of an orthorhombic YMnO(3) thin film by
      resonant soft x-ray and hard x-ray diffraction. We observed a temperature
      dependent incommensurate magnetic reflection below 45 K and a commensurate
      lattice-distortion reflection below 35 K. These results demonstrate that the
      ground state is composed of coexisting E-type and cycloidal states. Their
      different ordering temperatures clarify the origin of the large polarization to
      be caused by the E-type antiferromagnetic states in the orthorhombic YMnO(3) thin
      film.

PMID- 22400886
TI  - Spin wave diffraction and perfect imaging of a grating.
AB  - We study the diffraction of Damon-Eshbach-type spin waves incident on a one
      dimensional grating realized by microslits in a thin Permalloy film. By means of
      time-resolved scanning Kerr microscopy, we observe unique diffraction patterns
      behind the grating which exhibit replications of the spin wave field at the
      slits. We show that these spin wave images, with details finer than the
      wavelength of the incident Damon-Eshbach spin wavelength, arise from the strongly
      anisotropic spin wave dispersion.

PMID- 22400887
TI  - Complete optical absorption in periodically patterned graphene.
AB  - We demonstrate that 100% light absorption can take place in a single patterned
      sheet of doped graphene. General analysis shows that a planar array of small
      particles with losses exhibits full absorption under critical-coupling conditions
      provided the cross section of each individual particle is comparable to the area
      of the lattice unit cell. Specifically, arrays of doped graphene nanodisks
      display full absorption when supported on a substrate under total internal
      reflection and also when lying on a dielectric layer coating a metal. Our results
      are relevant for infrared light detectors and sources, which can be made tunable
      via electrostatic doping of graphene.

PMID- 22400888
TI  - Atomic structure of highly strained BiFeO3 thin films.
AB  - We determine the atomic structure of the pseudotetragonal T phase and the
      pseudorhombohedral R phase in highly strained multiferroic BiFeO(3) thin films by
      using a combination of atomic-resolution scanning transmission electron
      microscopy and electron energy-loss spectroscopy. The coordination of the Fe
      atoms and their displacement relative to the O and Bi positions are assessed by
      direct imaging. These observations allow us to interpret the electronic structure
      data derived from electron energy-loss spectroscopy and provide evidence for the
      giant spontaneous polarization in strained BiFeO(3) thin films.

PMID- 22400889
TI  - Density functional theory for Baxter's sticky hard spheres in confinement.
AB  - It has recently been shown that a free energy for Baxter's sticky hard-sphere
      fluid is uniquely defined within the framework of fundamental measure theory
      (FMT) for the inhomogeneous hard-sphere fluid, provided that it obeys scaled
      particle theory and the Percus-Yevick (PY) result for the direct correlation
      function [H. Hansen-Goos and J. S. Wettlaufer, J. Chem. Phys. 134, 014506
      (2011)]. Here, combining FMT weighted densities with a new vectorial weighted
      density, we regularize the divergences of the associated strongly confined limit.
      The free energy that emerges is exact in the zero-dimensional limit, leaves the
      underlying equation of state unaffected, and yields a direct correlation function
      distinct from that of PY. Comparison with simulation data for both the bulk pair
      correlation function and the density profiles in confinement shows that the new
      theory is significantly more accurate than the PY-based results.

PMID- 22400890
TI  - Developed smectics: when exact solutions agree.
AB  - In the limit where the bending modulus vanishes, we construct layer
      configurations with arbitrary dislocation textures by exploiting a connection
      between uniformly spaced layers in two dimensions and developable surfaces in
      three dimensions. We then show how these focal textures can be used to construct
      layer configurations with finite bending modulus.

PMID- 22400891
TI  - Imaging the ultrasmall-angle x-ray scattering distribution with grating
      interferometry.
AB  - X-ray imaging with grating interferometry has previously been regarded as a
      technique providing information only in direct space. It delivers absorption,
      phase, and dark-field contrast, which can be viewed as parameters of the
      underlying but unresolved scattering distribution. Here, we present a method that
      provides the ultrasmall-angle x-ray scattering distribution and, thus, allows
      simultaneous access to direct and reciprocal space information.

PMID- 22400892
TI  - DNA transport and delivery in thermal gradients near optofluidic resonators.
AB  - Heat generation and its impact on DNA transport in the vicinity of an optofluidic
      silicon photonic crystal resonator are studied theoretically and experimentally.
      The temperature rise is measured to be as high as 57 K for 10 mW of input power.
      The resulting optical trapping and biomolecular sensing properties of these
      devices are shown to be strongly affected by the combination of buoyancy driven
      flow and thermophoresis. Specifically, the region around the electromagnetic hot
      spot is depleted in biomolecules because of a high free energy barrier.

PMID- 22400893
TI  - Simple model for the deformation-induced relaxation of glassy polymers.
AB  - Glassy polymers show "strain hardening": at constant extensional load, their flow
      first accelerates, then arrests. Recent experiments have found this to be
      accompanied by a striking and unexplained dip in the segmental relaxation time.
      Here we explain such behavior by combining a minimal model of flow-induced
      liquefaction of a glass with a description of the stress carried by strained
      polymers, creating a nonfactorable interplay between aging and strain-induced
      rejuvenation. Under constant load, liquefaction of segmental motion permits
      strong flow that creates polymer-borne stress. This slows the deformation enough
      for the segmental modes to revitrify, causing strain hardening.

PMID- 22400894
TI  - Comment on "Hawking radiation, Unruh radiation, and the equivalence principle".

PMID- 22400896
TI  - Intracardiac masses in young Africans: case reports and a brief review of the
      literature.
AB  - Intracardiac masses in the young occur in some conditions that are prevalent in
      Africa. Although usually non-malignant, they may present with refractory heart
      failure and other complications that can be fatal. In the majority of cases, the
      aetiologic differentiation can be achieved by careful history, physical
      examination, basic laboratory tests, and transthoracic echocardiography. We
      report three cases in young Africans and discuss the aetiology, clinical
      presentation, diagnosis, management, and outcome of selected conditions in
      resource-limited settings.

PMID- 22400897
TI  - Interaction of nucleic acids with the glycocalyx.
AB  - Mammalian cells resist the uptake of nucleic acids. The lipid bilayer of the
      plasma membrane presents one barrier. Here, we report on a second physicochemical
      barrier for uptake. To create a sensitive probe for nucleic acid-cell
      interactions, we synthesized fluorescent conjugates in which lipids are linked to
      DNA oligonucleotides. We found that these conjugates incorporate readily into the
      plasma membrane but are not retained there. Expulsion of lipid-oligonucleotide
      conjugates from the plasma membrane increases with oligonucleotide length.
      Conversely, the incorporation of conjugates increases markedly in cells that lack
      the major anionic components of the glycocalyx, sialic acid and
      glycosaminoglycans, and in cells that had incorporated highly cationic lipids
      into their plasma membrane. We conclude that anionic oligosaccharides provide a
      formidable barrier to the uptake of nucleic acids by mammalian cells. This
      conclusion has implications for genomic stability, as well as the delivery of
      genes and siRNAs into mammalian cells.

PMID- 22400899
TI  - Laxative effects of partially defatted flaxseed meal on normal and experimental
      constipated mice.
AB  - BACKGROUND: Constipation is a very common health problem in the world. Intake of
      sufficient amount of dietary fibers is a cornerstone in the prevention and
      treatment of constipation. As a traditional medicine, flaxseed has been used to
      treat constipation for centuries, but the controlled trials are rare. The purpose
      of the present study was to assess that whether partially defatted flaxseed meal
      (PDFM) has the potential role to facilitate fecal output in normal and
      experimental constipated mice. METHODS: After supplemented with 2.5%, 5% and 10%
      (w/w) PDFM (L-, M- and H-PDFM) for 14 days, the constipation models of mice were
      induced by atropine-diphenoxylate. The small intestinal transit rates, start time
      of defecation, amount of defecation and wet weight of feces were researched in
      normal and constipation model mice. RESULTS: M- and H-PDFM significantly increase
      small intestinal transit rates in constipation model mice. All dose of PDFM
      markedly shortened the start time of defecation and M- and H-PDFM significantly
      increase stool frequency and weight in both normal and constipation model mice.
      CONCLUSIONS: PDFM may be a useful laxative to facilitate fecal output in normal
      and constipation conditions.

PMID- 22400900
TI  - Facile syntheses of 3-hydroxyflavones.
AB  - Modification of the present synthetic methods led to the syntheses of 3
      hydroxyflavones in a shorter reaction time, with simple purification and higher
      yields. Application of the method provided the syntheses of 3HFs having a
      hydroxyl group on the phenyl ring (ring B) in one step, which is an improvement
      compared to the four steps, long reaction time, and low yield using the current
      method available in the literature.

PMID- 22400901
TI  - Does intermittent pneumatic compression reduce the risk of post stroke deep vein
      thrombosis? The CLOTS 3 trial: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Approximately 80,000 patients each year are admitted to U.K.
      hospitals with an acute stroke and are immobile. At least 10% will develop a
      proximal deep vein thrombosis in the first month and 1.5% a pulmonary embolus.
      Although hydration, antiplatelet treatment and early mobilisation may reduce the
      risk of deep vein thrombosis, there are currently no preventive strategies which
      have been clearly shown to be both effective and safe. Anticoagulation increases
      the risks of bleeding and compression stockings are ineffective. Systematic
      reviews of small randomized trials of intermittent pneumatic compression have
      shown that this reduces the risk of deep vein thrombosis in patients undergoing
      surgery, but that there are few data concerning its use after stroke. The CLOTS
      trial 3 aims to determine whether, compared with best medical care, best medical
      care plus intermittent pneumatic compression in immobile stroke patients reduces
      the risk of proximal deep vein thrombosis. METHODS/DESIGN: CLOTS Trial 3 is a
      parallel group multicentre trial; with centralized randomisation (minimisation)
      to ensure allocation concealment. Over 80 centres in the U.K. will recruit 2800
      immobile stroke patients within the first 3 days of their hospital admission.
      Patients will be allocated to best medical care or best medical care plus
      intermittent pneumatic compression. Ultrasonographers will perform a Compression
      Duplex Ultrasound Scan to detect deep vein thrombosis in each treatment group at
      about 7-10 days and 25-30 days. The primary outcome cluster includes symptomatic
      or asymptomatic deep vein thrombosis in the popliteal or femoral veins detected
      on either scan. Patients are then followed up by postal or telephone
      questionnaire at 6 months from randomisation to detect later symptomatic deep
      vein thrombosis and pulmonary emboli and to establish their functional outcome
      (Oxford handicap scale) and quality of life (EQ5D-3 L). The ultrasonographers
      performing the scans are blinded to treatment allocation, whereas the patients
      and caregivers are not. The trial has 90% power to detect a 4% absolute
      difference in risk of the primary outcome and includes a health economic
      analysis. DISCUSSION: The trial started recruitment in Dec 2008 and will complete
      recruitment during 2012. It will report results in 2013. TRIAL REGISTRATION
      NUMBER: ISRCTN: ISRCTN93529999.

PMID- 22400902
TI  - De novo sequencing of circulating miRNAs identifies novel markers predicting
      clinical outcome of locally advanced breast cancer.
AB  - BACKGROUND: MicroRNAs (miRNAs) have been recently detected in the circulation of
      cancer patients, where they are associated with clinical parameters. Discovery
      profiling of circulating small RNAs has not been reported in breast cancer (BC),
      and was carried out in this study to identify blood-based small RNA markers of BC
      clinical outcome. METHODS: The pre-treatment sera of 42 stage II-III locally
      advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT)
      followed by surgical tumor resection were analyzed for marker identification by
      deep sequencing all circulating small RNAs. An independent validation cohort of
      26 stage II-III BC patients was used to assess the power of identified miRNA
      markers. RESULTS: More than 800 miRNA species were detected in the circulation,
      and observed patterns showed association with histopathological profiles of BC.
      Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and
      inflammatory BC were identified. The relative levels of selected miRNAs measured
      by PCR showed consistency with their abundance determined by deep sequencing. Two
      circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with
      clinical outcomes, including NCT response and relapse with metastatic disease. In
      the validation cohort, higher levels of circulating miR-122 specifically
      predicted metastatic recurrence in stage II-III BC patients. CONCLUSIONS: Our
      study indicates that certain miRNAs can serve as potential blood-based biomarkers
      for NCT response, and that miR-122 prevalence in the circulation predicts BC
      metastasis in early-stage patients. These results may allow optimized
      chemotherapy treatments and preventive anti-metastasis interventions in future
      clinical applications.

PMID- 22400903
TI  - Portable bedside ultrasound: the visual stethoscope of the 21st century.
AB  - Over the past decade technological advances in the realm of ultrasound have
      allowed what was once a cumbersome and large machine to become essentially hand
      held. This coupled with a greater understanding of lung sonography has
      revolutionized our bedside assessment of patients. Using ultrasound not as a
      diagnostic test, but instead as a component of the physical exam, may allow it to
      become the stethoscope of the 21st century.

PMID- 22400904
TI  - Extranodal rosai-dorfman disease presenting as a solitary mass with human
      herpesvirus 6 detection in a pediatric patient.
AB  - In Rosai-Dorfman disease (RDD), exclusive extranodal involvement with lesions
      limited to the kidneys is very uncommon and has been described only in adult
      patients. Occasionally, human herpesvirus 6 (HHV-6) has also been detected in RDD
      tissue samples. We present the case of a 7-year-old boy referred to our center
      presenting a single solid mass in the right kidney measuring 3.4 cm, detected
      both on contrast computed tomography and magnetic resonance imaging. Surgical
      excision was successfully completed, and the pathology report informed
      characteristic histopathology and immmunohistochemistry features of RDD. Human
      herpesvirus 6 was detected and amplified by polymerase chain reaction, as well as
      by immunohistochemistry. We discuss imaging and histology-based differential
      diagnoses in the pediatric age group. Although RDD is a rare histiocytic disorder
      of unknown etiology and pathogenesis, the presence of HHV-6 observed in this case
      supports the possibility of an abnormal immunologic response linked to viral
      presence.

PMID- 22400905
TI  - In-vitro and in-vivo binding activity of chicken egg yolk immunoglobulin Y (IgY)
      against gliadin in food matrix.
AB  - Chicken egg yolk immunoglobulin Y (IgY) is a promising alternative for the
      prevention of enteric gliadin absorption, the predisposing factor of celiac
      disease (CD). IgY antibody was produced from the egg yolk of Single Comb White
      Leghorn chickens during the immunization period for the development of an oral
      immunotherapeutic agent. Here, we report the potential use of spray dried IgY
      antibody formulation using sugar protectants (mannitol, sorbitol, or
      microcrystalline cellulose powder (MCCP)). The long-term stability of the spray
      dried egg yolk powder formulated with 37.5% mannitol (EYP-M) preserved IgY
      antibody activity at 99.9%, which was significantly higher than that with other
      protectants (p < 0.05). In a dissolution test, the EYP-M shows 82.4% IgY activity
      after 2 h in simulated gastric fluid (SGF). A competitive ELISA at 50% inhibition
      (IC(50)) shows that 1.6 mg/mL EYP-M bound to 7.6 mg/mL and 10.5 mg/mL gliadin in
      SGF without and with food matrix conditions, respectively, whereas in simulated
      intestinal fluid, the formulation bound to 10 mg/mL gliadin, regardless of a food
      matrix. In-vivo study: BALB/c mice fed with EYP-M and gliadin at a ratio of 1:5
      (w/w) demonstrated that gliadin absorption in the gastrointestinal tract was
      minimal at <1%. Thus, EYP-M containing IgY antibody may be used in CD patients to
      eliminate the effects of ingested toxic gliadin.

PMID- 22400908
TI  - Coordination of methyl coenzyme M and coenzyme M at divalent and trivalent nickel
      cyclams: model studies of methyl coenzyme M reductase active site.
AB  - Divalent and trivalent nickel complexes of 1,4,8,11-tetraazacyclotetradecane,
      denoted as cyclam hereafter, coordinated by methyl coenzyme M (MeSCoM(-)) and
      coenzyme M (HSCoM(-)) have been synthesized in the course our model studies of
      methyl coenzyme M reductase (MCR). The divalent nickel complexes
      Ni(cyclam)(RSCoM)(2) (R = Me, H) have two trans-disposed RSCoM(-) ligands at the
      nickel(II) center as sulfonates, and thus, the nickels have an octahedral
      coordination. The SCoM(2-) adduct Ni(cyclam)(SCoM) was also synthesized, in which
      the SCoM(2-) ligand chelates the nickel via the thiolate sulfur and a sulfonate
      oxygen. The trivalent MeSCoM adduct [Ni(cyclam)(MeSCoM)(2)](OTf) was synthesized
      by treatment of [Ni(cyclam)(NCCH(3))(2)](OTf)(3) with ((n)Bu(4)N)[MeSCoM]. A
      similar reaction with ((n)Bu(4)N)[HSCoM] did not afford the corresponding
      trivalent HSCoM(-) adduct, but rather the divalent nickel complex polymer [
      Ni(II)(cyclam)(CoMSSCoM)-](n) was obtained, in which the terminal thiol of HSCoM(
      ) was oxidized to the disulfide (CoMSSCoM)(2-) by the Ni(III) center.

PMID- 22400907
TI  - Lithium in pregnancy: the need to treat, the duty to ensure safety.
AB  - INTRODUCTION: Untreated bipolar disorder during pregnancy leads to detrimental
      repercussions on the mother-infant pair's health. Despite different drugs having
      been proposed as mood stabilizers, lithium remains the first-choice agent for
      preventing mood changes. AREAS COVERED: Analyzing up-to-date information on the
      reproductive safety of lithium and providing practice guidelines to optimize its
      use during pregnancy. EXPERT OPINION: Findings from prospective and case-control
      studies confirm an increased, specific risk of Ebstein's anomaly (4.45-7.6/1000
      live births), although lower than that previously reported. A potential increase
      in the risk of neural tube defects should also be taken into consideration.
      Moreover, several perinatal complications may occur, and even in the presence of
      relatively low infant serum levels, in the case of drug exposure during late
      pregnancy. Despite such concerns, lithium should still be considered the first
      choice agent for treating bipolar disorder in pregnancy. Indeed, the U.S. FDA
      recently issued a new warning regarding the reproductive safety of
      antipsychotics. Moreover, the risk of fetal valproate/carbamazepine syndrome (and
      the confirmed neurodevelopmental teratogenicity of valproate) contraindicates the
      use of both medications, whereas the use of lamotrigine is limited by efficacy
      concerns. However, women who need lithium treatment during pregnancy should be
      carefully monitored: a strict gynecologic and psychiatric surveillance and,
      probably, preconception folate supplementation is highly advisable. Moreover,
      delivery should be programmed in Neonatal Intensive Care Units to ensure optimal
      management of potential iatrogenic perinatal complications.

PMID- 22400906
TI  - Specificity of transcranial sonography in parkinson spectrum disorders in
      comparison to degenerative cognitive syndromes.
AB  - BACKGROUND: Hyperechogenicity of the substantia nigra (SN+), detected by
      transcranial sonography (TCS), was reported as a characteristic finding in
      Parkinson's disease (PD), with high diagnostic accuracy values, when compared
      mainly to healthy controls or essential tremor (ET) group. However, some data is
      accumulating that the SN + could be detected in other neurodegenerative and even
      in non-neurodegenerative disorders too. Our aim was to estimate the diagnostic
      accuracy of TCS, mainly focusing on the specificity point, when applied to a
      range of the parkinsonian disorders, and comparing to the degenerative cognitive
      syndromes. METHODS: A prospective study was carried out at the Hospital of
      Lithuanian University of Health Sciences from January until September 2011.
      Initially, a TCS and clinical examination were performed on 258 patients and 76
      controls. The General Electric Voluson 730 Expert ultrasound system was used.
      There were 12.8% of cases excluded with insufficient temporal bones, and 4.3%
      excluded with an unclear diagnosis. The studied sample consisted of the groups:
      PD (n = 71, 33.2%), ET (n = 58, 27.1%), PD and ET (n = 10, 4.7%), atypical
      parkinsonian syndromes (APS) (n = 3, 1.4%), hereditary neurodegenerative
      parkinsonism (HDP) (n = 3, 1.4%), secondary parkinsonism (SP) (n = 23, 10.8%),
      mild cognitive impairment (MCI) (n = 33, 15.4%), dementia (n = 13, 6.1%), and
      control (n = 71). RESULTS: There were 80.3% of PD patients at stages 1 & 2
      according to Hoehn and Yahr. At the cut-off value of 0.20 cm2 of the SN+, the
      sensitivity for PD was 94.3% and the specificity - 63.3% (ROC analysis, AUC
      0.891), in comparison to the rest of the cohort. At the cut-off value of 0.26
      cm2, the sensitivity was 90% and the specificity 82.4%.The estimations for the
      lowest specificity for PD, in comparison to the latter subgroups (at the cut-off
      values of 0.20 cm2 and 0.26 cm2, respectively) were: 0% and 33.3% to APS, 33.3%
      and 66.7% to HDP, 34.8% and 69.6% to SP, 55.2% and 82.8% to ET, 75% and 91.7% to
      dementia. CONCLUSIONS: The high sensitivity of the test could be employed as a
      valuable screening tool. But TCS is more useful as a supplementary diagnostic
      method, due to the specificity values not being comprehensive.

PMID- 22400909
TI  - Antioxidant and cytoprotective effects of oligomeric and polymeric procyanidin
      fractions from defatted grape seed in PC12 cells.
AB  - In this study, a crude polyphenol extract (CPE) from defatted grape seeds was
      evaluated for antioxidant and cytoprotective effects in PC12 cells. The CPE was
      then fractionated into a catechin and oligomeric procyanidin fraction
      (F(cat+olig)) and a polymeric procyanidin fraction (F(pol)), and the
      bioactivities of the fractions were evaluated individually. F(pol) was the
      richest in total polyphenol, total flavonoid, and polymeric procyanidin but
      contained less flavan-3-ol than F(cat+olig). Consistent with these results,
      F(pol) had the highest 2,2-diphenyl-beta-picrylhydrazyl radical scavenging
      activity and reducing power. Both F(cat+olig) and F(pol) had higher 2,2'-azino
      bis(3-ethylbenzthiazoline-6-sulfonic) acid radical scavenging activity than CPE.
      The resistance of PC12 cells against oxidative stress, after pretreatment with
      F(pol) (200 MUg/mL) for 9 h, was 100.7+/-2.9% of that in the control. Moreover,
      pretreating these cells with F(cat+olig) and F(pol) significantly decreased
      reactive oxygen species generation. These results provide information on a
      potential new source of antioxidants in the form of a functional food derived
      from an agricultural by-product.

PMID- 22400910
TI  - Inhibition of acetylcholinesterase activity and Fe2+-induced lipid peroxidation
      in rat brain in vitro by some citrus fruit juices.
AB  - This study sought to characterize the effects of some citrus fruit juices
      (shaddock [Citrus maxima], grapefruit [Citrus paradisii], lemon [Citrus limoni],
      orange [Citrus sinensis], and tangerine [Citrus reticulata]) on
      acetylcholinesterase activity in vitro. The total phenolic content, radical
      scavenging abilities, and inhibition of Fe(2+)-induced malondialdehyde (MDA)
      production in rats brain homogenate in vitro were also assessed. Orange had
      significantly (P<.05) higher phenolic content than the other juices. The juices
      scavenged 1,1-diphenyl-2-picrylhydrazyl and hydroxyl radicals in a dose-dependent
      manner with orange having the highest scavenging ability. Furthermore, the juices
      inhibited Fe(2+)-induced MDA production in rat brain homogenate in a dose
      dependent manner with shaddock having the highest inhibitory ability.
      Acetylcholinesterase activity was also inhibited in vitro by the juices in a dose
      dependent manner. The inhibition of acetylcholinesterase activity and antioxidant
      properties of the citrus juices could make them a good dietary means for the
      management of Alzheimer's disease.

PMID- 22400911
TI  - Effect of blueberry polyphenols on 3T3-F442A preadipocyte differentiation.
AB  - Today obesity is an epidemic, and its prevalence has increased significantly over
      the last few decades. To avoid excessive accumulation of fat, optimum energy
      intake along with regular exercise is mandatory. Polyphenols present in green
      tea, grape seeds, orange, and grapefruit combat adipogenesis at the molecular
      level and also induce lipolysis. However, very little is known regarding the role
      of blueberry polyphenols on adipocyte differentiation. Hence we tested the dose
      dependent effects of blueberry polyphenols on mouse 3T3-F442A preadipocyte
      differentiation and lipolysis. 3T3-F442A preadipocytes were incubated with three
      doses of blueberry polyphenols (150, 200, and 250 MUg/mL [BB-150, BB-200, and BB
      250, respectively]), and intracellular lipid content, cell proliferation, and
      lipolysis were assayed. Blueberry polyphenols suppressed adipocyte
      differentiation determined by Oil Red-O staining and AdipoRed assay.
      Intracellular lipid content in control (11,385.51+/-1,169.6 relative fluorescence
      units) was significantly higher (P<.05) than with the three doses of blueberry
      polyphenols (8336.86+/-503.57, 4235.67+/-323.17, and 3027.97+/-346.61,
      respectively). This corresponds to a reduction of 27%, 63%, and 74%,
      respectively. Cell proliferation was observed to be significantly higher in the
      control (0.744+/-0.035 optical density units) than with BB-150 (0.517+/-0.031),
      BB-200 (0.491+/-0.023), and BB-250 (0.455+/-0.012). However, when tested for
      lipolysis, there was no significant difference observed among the groups. We
      conclude that blueberry polyphenols may play an effective role in inhibiting
      adipogenesis and cell proliferation.

PMID- 22400912
TI  - Chemical guiding of magnetic nanoparticles in dispersed media containing poly
      (methylmethacrylate-co-vinylpyrrolidone).
AB  - The differential reactivity of methylmethacrylate (MMA) and vinylpyrrolidone (VP)
      in free radical copolymerization, with stirring in methanol, renders an
      emulsified two phase system. The dispersed and continuous liquid phases contain
      copolymers rich in MMA and VP, respectively. When Fe(3)O(4) magnetic
      nanoparticles (mNPs) stabilized with tetramethylammonium hydroxide are added to
      this emulsion, the mNPs are located in the continuous phase. Very small chemical
      changes in the methacrylic or vinylic chains are able to guide the mNP toward the
      interface or to the inside of the dispersed phase since quite a selective
      functionalization of each phase may be achieved separately. Thus, a small
      addition of methacrylic acid as comonomer (0.5% molar) guides all of the mNPs to
      the interface while a 0.5% molar of sulfopropyl methacrylate induces the
      migration of all mNPs to the dispersed phase. When 0.5% molar of a VP derivative
      bearing sulfonate functionality is added, the mNPs are found both in the
      interface and in the continuous phase. The addition of water allows solid MMA
      based microspheres to be obtained incorporating the mNPs selectively either at
      the surface or in the core.

PMID- 22400913
TI  - Short-term effect of leflunomide in patients with Takayasu arteritis: an
      observational study.
AB  - OBJECTIVES: To evaluate the efficacy of leflunomide in controlling disease
      activity in patients with Takayasu arteritis (TA) refractory or intolerant to
      conventional treatment. METHODS: We conducted a prospective open-label study of
      15 TA patients (mean age 36.2 years) with active disease based on clinical
      assessment, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and
      magnetic resonance angiography (MRA). Patients received leflunomide 20 mg/day for
      at least 6 months and were followed up for a mean of 9.1 months. Adverse events
      attributable to leflunomide were recorded. RESULTS: At baseline, 14 TA patients
      had active disease despite therapy with corticosteroids and immunosuppressive
      agents, while one patient had intolerance to current treatment. In the follow-up
      visit, we found a significant decrease in the frequency of patients with active
      TA (93% vs. 20%, p = 0.002), in the mean daily dose of prednisone (34.2 vs. 13.9
      mg, p < 0.001) and in the median values of ESR (29.0 vs. 27.0 mm/h, p = 0.012)
      and CRP (10.3 vs. 5.3 mg/L, p = 0.012). Two patients (13.3%) developed new
      angiographic lesions in the follow-up MRA. Three patients (20%) experienced mild
      adverse events during the study and none discontinued therapy. CONCLUSIONS: This
      is the first open-label study to demonstrate improvement in disease activity and
      acute phase reactants with 20 mg/day of leflunomide in TA patients who were
      refractory or intolerant to conventional therapy with corticosteroids and
      immunosuppressive agents. Leflunomide was safe and a steroid-sparing effect was
      observed. A double-blind controlled study is desirable to confirm this finding.

PMID- 22400914
TI  - Expression of genes of Trichoderma harzianum in response to the presence of
      cadmium in the substrate.
AB  - Trichoderma harzianum is a very important fungus for the reduction of the amount
      of heavy metals resulting from agricultural and industrial activities. This
      filamentous fungus has been shown to be tolerant towards several heavy metals
      (e.g. Cd, Pb, Zn, Ni and Mn), but the mechanism underlying this tolerance is not
      entirely understood. In this study, we confirmed the ability of T. harzianum to
      grow in the presence of cadmium and observed a significant stimulation of its
      growth in the presence of mercury. A molecular approach to investigate the
      cadmium tolerance mechanisms was carried out by the application of the
      suppression subtractive hybridisation (SSH) technique. To this end, we have used
      a particular strategy to discriminate cadmium-induced differentially expressed
      genes from those generally expressed upon heavy metal treatment. Several genes
      (109) were found to be overexpressed in the presence of cadmium, confirming the
      dramatic metabolic modification underlying the metal stress response of the
      fungus.

PMID- 22400915
TI  - Targeted deletion of nrf2 impairs lung development and oxidant injury in neonatal
      mice.
AB  - AIMS: Nrf2 is an essential transcription factor for protection against oxidant
      disorders. However, its role in organ development and neonatal disease has
      received little attention. Therapeutically administered oxygen has been
      considered to contribute to bronchopulmonary dysplasia (BPD) in prematurity. The
      current study was performed to determine Nrf2-mediated molecular events during
      saccular-to-alveolar lung maturation, and the role of Nrf2 in the pathogenesis of
      hyperoxic lung injury using newborn Nrf2-deficient (Nrf2(-/-)) and wild-type
      (Nrf2(+/+)) mice. RESULTS: Pulmonary basal expression of cell cycle, redox
      balance, and lipid/carbohydrate metabolism genes was lower while lymphocyte
      immunity genes were more highly expressed in Nrf2(-/-) neonates than in Nrf2(+/+)
      neonates. Hyperoxia-induced phenotypes, including mortality, arrest of saccular
      to-alveolar transition, and lung edema, and inflammation accompanying DNA damage
      and tissue oxidation were significantly more severe in Nrf2(-/-) neonates than in
      Nrf2(+/+) neonates. During lung injury pathogenesis, Nrf2 orchestrated expression
      of lung genes involved in organ injury and morphology, cellular
      growth/proliferation, vasculature development, immune response, and cell-cell
      interaction. Bioinformatic identification of Nrf2 binding motifs and augmented
      hyperoxia-induced inflammation in genetically deficient neonates supported Gpx2
      and Marco as Nrf2 effectors. INNOVATION: This investigation used lung
      transcriptomics and gene targeted mice to identify novel molecular events during
      saccular-to-alveolar stage transition and to elucidate Nrf2 downstream mechanisms
      in protection from hyperoxia-induced injury in neonate mouse lungs. CONCLUSION:
      Nrf2 deficiency augmented lung injury and arrest of alveolarization caused by
      hyperoxia during the newborn period. Results suggest a therapeutic potential of
      specific Nrf2 activators for oxidative stress-associated neonatal disorders
      including BPD.

PMID- 22400916
TI  - Waikialoid A suppresses hyphal morphogenesis and inhibits biofilm development in
      pathogenic Candida albicans.
AB  - A chemically prolific strain of Aspergillus was isolated from a soil sample
      collected near Waikiki Beach, Honolulu, Hawaii. The fungus produced several
      secondary metabolites, which were purified and placed in our natural products
      library and were later screened for substances capable of inhibiting biofilm
      formation by Candida albicans. It was determined that one of the secondary
      metabolites from the Hawaiian fungal isolate, a new complex prenylated indole
      alkaloid named waikialoid A (1), inhibited biofilm formation with an IC(50) value
      of 1.4 MUM. Another structurally unrelated, presumably polyketide metabolite,
      waikialide A (15), also inhibited C. albicans biofilm formation, but was much
      less potent (IC(50) value of 32.4 MUM). Microscopy studies revealed that compound
      1 also inhibited C. albicans hyphal morphogenesis. While metabolite 1 appears
      ineffective at disrupting preformed biofilms, the accumulated data indicate that
      the new compound may exert its activity against C. albicans during the early
      stages of surface colonization involving cell adherence, hyphal development,
      and/or biofilm assembly. Unlike some other stephacidin/notoamide compounds,
      metabolite 1 was not cytotoxic to fungi or human cells (up to 200 MUM), which
      makes this an intriguing model compound for studying the adjunctive use of
      biofilm inhibitors in combination with standard antifungal antibiotics.

PMID- 22400917
TI  - Fatness is not a factor of fitness: analysis of cardiorespiratory data from
      healthy children over an 8-year period.
AB  - PURPOSE: To evaluate exercise performance and body mass index in healthy children
      over an 8-year period in order to determine whether cardiorespiratory fitness has
      decreased relative to changes in body mass index in our patient population.
      METHOD: This study is a retrospective review of anthropometric and
      cardiorespiratory fitness data from our hospital's Exercise Physiology
      Laboratory's database on 1201 healthy children (6-18 years) with structurally
      normal hearts who performed one cycle ergometry test between 1999 and 2006.
      Subjects were stratified by gender and age. Body mass index was compared between
      1999-2002 (Early Group) and 2003-2006 (Late Group) and with national averages.
      Exercise outcome variables were maximal oxygen consumption, anaerobic threshold,
      physical working capacity indexed to body weight. Analysis of variance was used
      to detect differences between groups for each outcome variable. RESULTS: Body
      mass index was not significantly different from national data (p-value equals
      0.79) or between groups. A negative trend (p-value greater than 0.15 less than
      0.20) was observed among most indices of exercise performance between Early and
      Late Groups. Significantly lower anaerobic threshold was found among males
      between Early and Late Group (25.7 plus or minus 0.9 versus 23.4 plus or minus
      1.6 millilitres per kilogram per minute, p-value less than 0.01), and in physical
      working capacity among females between Early and Late Groups (2.9 plus or minus
      0.1 versus 2.7 plus or minus 0.1, p-value less than 0.05). CONCLUSIONS:
      Cardiorespiratory fitness in males and working capacity in females declined over
      time independent of body mass index. This suggests that other measures may need
      to be evaluated for promotion of overall cardiovascular health.

PMID- 22400918
TI  - Local unitary classification of arbitrary dimensional multipartite pure states.
AB  - We propose a practical entanglement classification scheme for general
      multipartite pure states in arbitrary dimensions under local unitary equivalence
      by exploiting the high order singular value decomposition technique and local
      symmetries of the states. By virtue of this scheme, the method of determining the
      local unitary equivalence of n-qubit states proposed by Kraus is extended to the
      case for arbitrary dimensional multipartite states.

PMID- 22400919
TI  - General second-order scalar-tensor theory and self-tuning.
AB  - Starting from the most general scalar-tensor theory with second-order field
      equations in four dimensions, we establish the unique action that will allow for
      the existence of a consistent self-tuning mechanism on Friedmann-Lemaitre
      Robertson-Walker backgrounds, and show how it can be understood as a combination
      of just four base Lagrangians with an intriguing geometric structure dependent on
      the Ricci scalar, the Einstein tensor, the double dual of the Riemann tensor, and
      the Gauss-Bonnet combination. Spacetime curvature can be screened from the net
      cosmological constant at any given moment because we allow the scalar field to
      break Poincare invariance on the self-tuning vacua, thereby evading the Weinberg
      no-go theorem. We show how the four arbitrary functions of the scalar field
      combine in an elegant way opening up the possibility of obtaining nontrivial
      cosmological solutions.

PMID- 22400920
TI  - Measurement of the cosmic-ray antiproton spectrum at solar minimum with a long
      duration balloon flight over antarctica.
AB  - The energy spectrum of cosmic-ray antiprotons (p's) from 0.17 to 3.5 GeV has been
      measured using 7886 p's detected by BESS-Polar II during a long-duration flight
      over Antarctica near solar minimum in December 2007 and January 2008. This shows
      good consistency with secondary p calculations. Cosmologically primary p's have
      been investigated by comparing measured and calculated p spectra. BESS-Polar II
      data show no evidence of primary p's from the evaporation of primordial black
      holes.

PMID- 22400921
TI  - Shallow water analogue of the standing accretion shock instability: experimental
      demonstration and a two-dimensional model.
AB  - Despite the sphericity of the collapsing stellar core, the birth conditions of
      neutron stars can be highly nonspherical due to a hydrodynamical instability of
      the shocked accretion flow. Here we report the first laboratory experiment of a
      shallow water analogue, based on the physics of hydraulic jumps. Both the
      experiment and its shallow water modeling demonstrate a robust linear instability
      and nonlinear properties of symmetry breaking, in a system which is one million
      times smaller and about one hundred times slower than its astrophysical analogue.

PMID- 22400922
TI  - Integrability of spinning particle motion in higher-dimensional rotating black
      hole spacetimes.
AB  - We study the motion of a classical spinning particle (with spin degrees of
      freedom described by a vector of Grassmann variables) in higher-dimensional
      general rotating black hole spacetimes with a cosmological constant. In all
      dimensions n we exhibit n bosonic functionally independent integrals of spinning
      particle motion, corresponding to explicit and hidden symmetries generated from
      the principal conformal Killing-Yano tensor. Moreover, we demonstrate that in 4-,
      5-, 6-, and 7-dimensional black hole spacetimes such integrals are in involution,
      proving the bosonic part of the motion integrable. We conjecture that the same
      conclusion remains valid in all higher dimensions. Our result generalizes the
      result of Page et al. [Phys. Rev. Lett. 98, 061102 (2007)] on complete
      integrability of geodesic motion in these spacetimes.

PMID- 22400923
TI  - Low-energy break in the spectrum of Galactic cosmic rays.
AB  - Measurements of the low-energy spectrum of Galactic cosmic rays (GCRs) by
      detectors on or near Earth are affected by solar modulation. To overcome this
      difficulty, we consider nearby molecular clouds as GCR detectors outside the
      Solar System. Using gamma-ray observations of the clouds by the Fermi telescope,
      we derive the spectrum of GCRs in the clouds from the observed gamma-ray emission
      spectrum. We find that the GCR spectrum has a low-energy break with the spectral
      slope hardening by DeltaGamma=1.1+/-0.3 at an energy of E=9+/-3  GeV. Detection
      of a low-energy break enables a measurement of GCR energy density in the
      interstellar space U=0.9+/-0.3  eV/cm{3}.

PMID- 22400924
TI  - Local Hamiltonian for spherically symmetric gravity coupled to a scalar field.
AB  - We present a gauge fixing of gravity coupled to a scalar field in spherical
      symmetry such that the Hamiltonian is an integral over space of a local density.
      Such a formulation had proved elusive over the years. As in any gauge fixing, it
      works for a restricted set of initial data. We argue that the set could be large
      enough to attempt a quantization the could include the important case of an
      evaporating black hole.

PMID- 22400925
TI  - First evidence of pep solar neutrinos by direct detection in Borexino.
AB  - We observed, for the first time, solar neutrinos in the 1.0-1.5 MeV energy range.
      We determined the rate of pep solar neutrino interactions in Borexino to be 3.1+/
      0.6{stat}+/-0.3{syst}  counts/(day.100  ton). Assuming the pep neutrino flux
      predicted by the standard solar model, we obtained a constraint on the CNO solar
      neutrino interaction rate of <7.9  counts/(day.100  ton) (95% C.L.). The absence
      of the solar neutrino signal is disfavored at 99.97% C.L., while the absence of
      the pep signal is disfavored at 98% C.L. The necessary sensitivity was achieved
      by adopting data analysis techniques for the rejection of cosmogenic {11}C, the
      dominant background in the 1-2 MeV region. Assuming the Mikheyev-Smirnov
      Wolfenstein large mixing angle solution to solar neutrino oscillations, these
      values correspond to solar neutrino fluxes of (1.6+/-0.3)*10{8}  cm{-2} s^{-1}
      and <7.7*10{8}  cm{-2} s{-1} (95% C.L.), respectively, in agreement with both the
      high and low metallicity standard solar models. These results represent the first
      direct evidence of the pep neutrino signal and the strongest constraint of the
      CNO solar neutrino flux to date.

PMID- 22400927
TI  - New finite-range droplet mass model and equation-of-state parameters.
AB  - The parameters in the macroscopic droplet part of the finite-range droplet model
      (FRDM) are related to the properties of the equation of state. In the FRDM (1992)
      version, the optimization of the model parameters was not sufficiently sensitive
      to variations of the compressibility constant K and the density-symmetry constant
      L to allow their determination. In the new, more accurate FRDM-2011a adjustment
      of the model constants to new and more accurate experimental masses allows the
      determination of L together with the symmetry-energy constant J. The optimization
      is still not sensitive to K which is therefore fixed at K=240  MeV. Our results
      are J=32.5+/-0.5  MeV and L=70+/-15  MeV and a considerably improved mass-model
      accuracy sigma=0.5700  MeV, with respect to the 2003 Atomic Mass Evaluation
      (AME2003) for FRDM-2011a, compared to sigma=0.669  MeV for FRDM (1992).

PMID- 22400926
TI  - Beam-target double-spin asymmetry A{LT} in charged pion production from deep
      inelastic scattering on a transversely polarized {3}He target at 1.4<Q{2}<2.7 
      GeV{2}.
AB  - We report the first measurement of the double-spin asymmetry A{LT} for charged
      pion electroproduction in semi-inclusive deep-inelastic electron scattering on a
      transversely polarized {3}He target. The kinematics focused on the valence quark
      region, 0.16<x<0.35 with 1.4<Q{2}<2.7  GeV{2}. The corresponding neutron A{LT}
      asymmetries were extracted from the measured {3}He asymmetries and proton over
      {3}He cross section ratios using the effective polarization approximation. These
      new data probe the transverse momentum dependent parton distribution function
      g{1T}{q} and therefore provide access to quark spin-orbit correlations. Our
      results indicate a positive azimuthal asymmetry for pi{-} production on {3}He and
      the neutron, while our pi{+} asymmetries are consistent with zero.

PMID- 22400928
TI  - Chiral effective field theory predictions for muon capture on deuteron and {3}He.
AB  - The muon-capture reactions {2}H(MU{-},nu{MU})nn and {3}He(MU{-},nu{MU}){3}H are
      studied with nuclear potentials and charge-changing weak currents, derived in
      chiral effective field theory. The low-energy constants (LECs) c{D} and c{E},
      present in the three-nucleon potential and (c{D}) axial-vector current, are
      constrained to reproduce the A=3 binding energies and the triton Gamow-Teller
      matrix element. The muon-capture rates on deuteron and {3}He are predicted to be
      399+/-3  sec{-1} and 1494+/-21  sec{-1}, respectively. The spread accounts for
      the cutoff sensitivity, as well as uncertainties in the LECs and electroweak
      radiative corrections. By comparing the calculated and precisely measured rates
      on {3}He, a value for the induced pseudoscalar form factor is obtained in good
      agreement with the chiral perturbation theory prediction.

PMID- 22400929
TI  - Determination of the structure of {31}ne by a fully microscopic framework.
AB  - We perform the first quantitative analysis of the reaction cross sections of {28
      32}Ne by {12}C at 240  MeV/nucleon, using the double-folding model with the
      Melbourne g matrix and the deformed projectile density calculated by
      antisymmetrized molecular dynamics. To describe the tail of the last neutron of
      {31}Ne, we adopt the resonating group method combined with antisymmetrized
      molecular dynamics. The theoretical prediction excellently reproduces the
      measured cross sections of {28-32}Ne with no adjustable parameters. The ground
      state properties of {31}Ne, i.e., strong deformation and a halo structure with
      spin parity 3/2{-}, are clarified.

PMID- 22400930
TI  - First direct mass measurement of the two-neutron halo nucleus 6He and improved
      mass for the four-neutron halo 8He.
AB  - The first direct mass measurement of {6}He has been performed with the TITAN
      Penning trap mass spectrometer at the ISAC facility. In addition, the mass of
      {8}He was determined with improved precision over our previous measurement. The
      obtained masses are m({6}He)=6.018 885 883(57)  u and m({8}He)=8.033 934 44(11) 
      u. The {6}He value shows a deviation from the literature of 4sigma. With these
      new mass values and the previously measured atomic isotope shifts we obtain
      charge radii of 2.060(8) and 1.959(16) fm for {6}He and {8}He, respectively. We
      present a detailed comparison to nuclear theory for {6}He, including new
      hyperspherical harmonics results. A correlation plot of the point-proton radius
      with the two-neutron separation energy demonstrates clearly the importance of
      three-nucleon forces.

PMID- 22400931
TI  - Analysis of gamma-ray production in neutral-current neutrino-oxygen interactions
      at energies above 200 MeV.
AB  - It has long been recognized that the observation of gamma rays originating from
      nuclear deexcitation can be exploited to identify neutral-current neutrino
      nucleus interactions in water-Cherenkov detectors. We report the results of a
      calculation of the neutrino- and antineutrino-induced gamma-ray production cross
      section for the oxygen target. Our analysis is focused on the kinematical region
      of neutrino energy larger than ~200  MeV, in which a single-nucleon knockout is
      known to be the dominant reaction mechanism. The numerical results have been
      obtained using for the first time a realistic model of the target spectral
      function, extensively tested against electron-nucleus scattering data. We find
      that at a neutrino energy of 600 MeV the fraction of neutral-current interactions
      leading to emission of gamma rays of energy larger than 6 MeV is ~41%, and that
      the contribution of the p_{3/2} state is overwhelming.

PMID- 22400932
TI  - Angular distributions for the complete photofragmentation of the Li atom.
AB  - We explore the complete breakup of the Li atom after absorption of a single
      photon, the purest example of the so-called four-body Coulomb problem. The
      resulting strongly correlated three-electron continuum is investigated by
      calculating the angular distributions of the ionized electrons using advanced
      close-coupling techniques. We find that the distributions are dominated by the
      Coulomb interactions between the electrons, that multiple break-up processes can
      be identified, and that the complex dynamics of the fragmentation process are
      evident for most scattering geometries.

PMID- 22400933
TI  - Fast path and polarization manipulation of telecom wavelength single photons in
      lithium niobate waveguide devices.
AB  - We demonstrate fast polarization and path control of photons at 1550 nm in
      lithium niobate waveguide devices using the electro-optic effect. We show
      heralded single photon state engineering, quantum interference, fast state
      preparation of two entangled photons, and feedback control of quantum
      interference. These results point the way to a single platform that will enable
      the integration of nonlinear single photon sources and fast reconfigurable
      circuits for future photonic quantum information science and technology.

PMID- 22400934
TI  - Plume fragmentation by bulk interactions in turbulent Rayleigh-Benard convection.
AB  - Using compressed gases with Prandtl numbers near 0.7, we obtained flow
      visualizations of turbulent Rayleigh-Benard convection in a cylindrical sample
      with an aspect ratio Gamma=D/L?10 (D is the diameter and L the height) by the
      shadowgraph method. Focusing on the plumes under the top plate, we found that
      their length had a log-normal distribution, suggesting a fragmentation process.
      Fragmentation events could be visually identified in the images and involved
      plume interactions with bulk fluctuations or upwelling domain walls. We found the
      mean spacing between plumes to vary with the Rayleigh number in proportion to the
      volume-averaged Kolmogorov length of the turbulent bulk fluctuations, providing
      further evidence for plume-bulk interactions.

PMID- 22400935
TI  - Discrete salt crystallization at the surface of a porous medium.
AB  - Efflorescence refers to crystallized salt structures that form at the surface of
      a porous medium. The challenge is to understand why these structures do not form
      everywhere at the surface of the porous medium but at some specific locations and
      why there exists an exclusion distance around an efflorescence where no new
      efflorescence forms. These are explained from a visualization experiment, pore
      network simulations and a simple efflorescence growth model.

PMID- 22400936
TI  - Focusing dynamics of high-energy density, laser-driven ion beams.
AB  - The dynamics of the focusing of laser-driven ion beams produced from concave
      solid targets was studied. Most of the ion beam energy is observed to converge at
      the center of the cylindrical targets with a spot diameter of 30  MUm, which can
      be very beneficial for applications requiring high beam energy densities. Also,
      unbalanced laser irradiation does not compromise the focusability of the beam.
      However, significant filamentation occurs during the focusing, potentially
      limiting the localization of the energy deposition region by these beams at
      focus. These effects could impact the applicability of such high-energy density
      beams for applications, e.g., in proton-driven fast ignition.

PMID- 22400938
TI  - Lattice dynamics of dense lithium.
AB  - We report low-frequency high-resolution Raman spectroscopy and ab-initio
      calculations on dense lithium from 40 to 200 GPa at low temperatures. Our
      experimental results reveal rich first-order Raman activity in the metallic and
      semiconducting phases of lithium. The computed Raman frequencies are in excellent
      agreement with the measurements. Free energy calculations provide a quantitative
      description and physical explanation of the experimental phase diagram only when
      vibrational effect are correctly treated. The study underlines the importance of
      zero-point energy in determining the phase stability of compressed lithium.

PMID- 22400937
TI  - X-ray diagnosis of the pressure induced Mott nonmetal-metal transition.
AB  - The evolution of the K-edge x-ray absorption near-edge spectroscopy (XANES)
      spectrum is investigated for an aluminum plasma expanding from the solid density
      down to 0.5  g/cm{3}, with temperatures lying from 5 down to 2 eV. The dense
      plasma is generated by nanosecond laser-induced shock compression. These
      conditions correspond to the density-temperature region where a metal-nonmetal
      transition occurs as the density decreases. This transition is directly observed
      in XANES spectra measurements through the progressive formation of a preedge
      structure for densities around 1.6  g/cm{3}. Ab initio calculations based on
      density functional theory and a jellium model have been efficiently tested
      through direct comparison with the experimental measurements and show that this
      preedge corresponds to the relocalization of the 3p atomic orbital as the system
      evolves from a dense plasma toward a partially ionized atomic fluid.

PMID- 22400939
TI  - Surface nanocrystallization of an ionic liquid.
AB  - Surface crystallization at the vapor-liquid interface of the ionic liquid (1
      butyl-3-methylimidazolium hexafluorophosphate) is observed in synchrotron x-ray
      diffraction studies. Sharp Bragg reflections emerge in grazing-angle x-ray
      diffraction patterns 37  degrees C above the bulk melting temperature, indicating
      the presence of a long-range ordered phase at the surface in coexistence with the
      bulk parent liquid. The unique structure of the vapor-liquid interface where
      butyl chains attached to the cations are expelled to the vapor side facilitates
      interionic electrostatic interactions that lead to the crystallization. Our
      results demonstrate the complexity of ionic-liquid structure with their tendency
      to spontaneously phase separate into nanodomains with finite correlation lengths
      in coexistence with the liquid phase. By virtue of interfacial boundary
      conditions, these nanodomains grow laterally to form quasi-two-dimensional
      crystals.

PMID- 22400940
TI  - Formation of Ge nanoripples on vicinal Si (1110): from Stranski-Krastanow seeds
      to a perfectly faceted wetting layer.
AB  - Ge growth on high-indexed Si (1110) is shown to result in the spontaneous
      formation of a perfectly {105} faceted one-dimensional nanoripple structure. This
      evolution differs from the usual Stranski-Krastanow growth mode because from
      initial ripple seeds a faceted Ge layer is formed that extends down to the
      heterointerface. Ab initio calculations reveal that ripple formation is mainly
      driven by lowering of surface energy rather than by elastic strain relief and the
      onset is governed by the edge energy of the ripple facets. Wavelike ripple
      replication is identified as an effective kinetic pathway for the transformation
      process.

PMID- 22400941
TI  - Direct experimental determination of grain boundary excess volume in metals.
AB  - The grain boundary excess volume, i.e., the grain boundary expansion, e{GB}, was
      experimentally determined for high-angle grain boundaries in nickel using the
      direct technique of high-precision difference dilatometry. Values of
      e{GB}=(0.35+/-0.04)*10{-10}  m and e{GB}=(0.32+/-0.04)*10{-10}  m were obtained
      by measuring the removal of grain boundary volume upon grain growth for two
      different types of ultrafine-grained samples. The results are discussed in
      comparison to values obtained so far from indirect techniques and from computer
      simulations. It demonstrates the strength of the presented novel, direct approach
      for grain boundary expansion measurements.

PMID- 22400942
TI  - Structure of iron to 1 Gbar and 40, 000 K.
AB  - First-principles calculations show that compression-induced electronic
      transitions produce a rich phase diagram featuring reentrant stability of the fcc
      phase with an extremum on the fcc to hcp boundary at 23 Mbar and 19 000 K,
      conditions similar to those expected at the center of super-Earth exoplanets.
      Transformations of hcp to fcc at 57 Mbar due to 4s to 3d electron transfer and
      from fcc to a body-centered structure at 320 Mbar due to hybridization of the 3d
      with the core 3p band are experimentally observable along a quasi-isentrope
      generated by laser-induced ramp compression.

PMID- 22400943
TI  - Quantum critical dynamics simulation of dirty boson systems.
AB  - Recently, the scaling result z=d for the dynamic critical exponent at the Bose
      glass to superfluid quantum phase transition has been questioned both on
      theoretical and numerical grounds. This motivates a careful evaluation of the
      critical exponents in order to determine the actual value of z. We study a model
      of quantum bosons at T=0 with disorder in 2D using highly effective worm Monte
      Carlo simulations. Our data analysis is based on a finite-size scaling approach
      to determine the scaling of the quantum correlation time from simulation data for
      boson world lines. The resulting critical exponents are z=1.8+/-0.05, nu=1.15+/
      0.03, and eta=-0.3+/-0.1, hence suggesting that z=2 is not satisfied.

PMID- 22400826
TI  - Measurement of the ZZ production cross section and limits on anomalous neutral
      triple gauge couplings in proton-proton collisions at sqrt[s] = 7 TeV with the
      ATLAS detector.
AB  - A measurement of the ZZ production cross section in proton-proton collisions at
      sqrt[s] = 7 TeV using data corresponding to an integrated luminosity of 1.02 fb(
      1) recorded by the ATLAS experiment at the LHC is presented. Twelve events
      containing two Z boson candidates decaying to electrons and/or muons are
      observed, with an expected background of 0.3 +/- 0.3(stat)(-0.3)(+0.4)(syst)
      events. The cross section measured in a phase-space region with good detector
      acceptance and for dilepton masses within the range 66 to 116 GeV is sigma(ZZ ->
      l+ l- l+ l-)(fid) = 19.4(-5.2)(+6.3)(stat)(-0.7)(+0.9)(syst) +/- 0.7(lumi) fb.
      The resulting total cross section for on-shell ZZ production, sigma(ZZ)(tot) =
      8.5(-2.3)(+2.7)(stat)(-0.3)(+0.4)(syst) +/- 0.3(lumi) pb, is consistent with the
      standard model expectation of 6.5(-0.2)(+0.3) pb calculated at the next-to
      leading order in QCD. Limits on anomalous neutral triple gauge boson couplings
      are derived.

PMID- 22400944
TI  - Strong magnetic fluctuations in a superconducting state of CeCoIn5.
AB  - We show results on the vortex core dissipation through current-voltage
      measurements under applied pressure and magnetic field in the superconducting
      phase of CeCoIn{5}. We find that as soon as the system becomes superconducting,
      the vortex core resistivity increases sharply as the temperature and magnetic
      field decrease. The sharp increase in flux-flow resistivity is due to
      quasiparticle scattering on critical antiferromagnetic fluctuations. The strength
      of magnetic fluctuations below the superconducting transition suggests that
      magnetism is complementary to superconductivity and therefore must be considered
      in order to fully account for the low-temperature properties of CeCoIn{5}.

PMID- 22400945
TI  - Convergence of energy scales on the approach to a local quantum critical point.
AB  - We find the emergence of strong correlations and universality on the approach to
      the quantum critical points of a two-impurity Anderson model. The two impurities
      are coupled by an interimpurity exchange interaction J and direct interaction
      U{12} and are hybridized with separate conduction channels. The low energy
      behavior is described in terms of renormalized parameters. We show that on the
      approach to the transitions to a local singlet and a local charged ordered state,
      the quasiparticle weight factor z->0, and the renormalized parameters can be
      expressed in terms of a single energy scale T{*}. The values of the renormalized
      interaction parameters in terms of T{*} can be predicted from the condition of
      continuity of the spin and charge susceptibilities, and correspond to strong
      correlation. These predictions are confirmed by the numerical renormalization
      group calculations, including the case when the on site interaction U=0.

PMID- 22400948
TI  - Direct observation of sub-100 fs mobile charge generation in a polymer-fullerene
      film.
AB  - The formation of mobile charges in a roll-to-roll processed poly-3-hexylthiophene
      fullerene bulk heterojunction film is observed directly by using transient
      terahertz spectroscopy with sub-100 fs temporal resolution. The transient
      terahertz ac conductivity reveals that 20% of the incident pump photons are
      converted into highly delocalized charges within the 40 fs, 3.1 eV pump pulse
      duration, which then rapidly becomes localized within 120 fs. Approximately 2/3
      of these carriers subsequently decay, possibly into an exciton, on a 1 ps time
      scale.

PMID- 22400950
TI  - Time-resolved two-photon photoemission of unoccupied electronic states of
      periodically rippled graphene on Ru(0001).
AB  - The unoccupied electronic states of epitaxially grown graphene on Ru(0001) have
      been explored by time- and angle-resolved two-photon photoemission. We identify a
      Ru derived resonance and a Ru/graphene interface state at 0.91 and 2.58 eV above
      the Fermi level, as well as three image-potential derived states close to the
      vacuum level. The most strongly bound, short-lived, and least dispersing image
      potential state is suggested to have some quantum-well character with a large
      amplitude below the graphene hills. The two other image-potential states are
      attributed to a series of slightly decoupled states. Their lifetimes and
      dispersions are indicative of electrons moving almost freely above the valley
      areas of the moire superstructure of graphene.

PMID- 22400946
TI  - Hall effect of spin-chirality origin in a triangular-lattice helimagnet
      Fe{1.3}Sb.
AB  - We report on a topological Hall effect possibly induced by scalar spin chirality
      in a quasi-two-dimensional helimagnet Fe{1+delta}Sb. In the low-temperature
      region where the spins on interstitial-Fe (concentration delta~0.3) intervening
      the 120 degrees  spin-ordered triangular planes tend to freeze, a nontrivial
      component of Hall resistivity with opposite sign of the conventional anomalous
      Hall term is observed under magnetic field applied perpendicular to the
      triangular-lattice plane. The observed unconventional Hall effect is ascribed to
      the scalar spin chirality arising from the heptamer spin clusters around the
      interstitial-Fe sites, which can be induced by the spin modulation by the
      Dzyaloshinsky-Moriya interaction.

PMID- 22400947
TI  - Optically engineering the topological properties of a spin Hall insulator.
AB  - Time-periodic perturbations can be used to engineer topological properties of
      matter by altering the Floquet band structure. This is demonstrated for the
      helical edge state of a spin Hall insulator in the presence of monochromatic
      circularly polarized light. The inherent spin structure of the edge state is
      influenced by the Zeeman coupling and not by the orbital effect. The photocurrent
      (and the magnetization along the edge) develops a finite, helicity-dependent
      expectation value and turns from dissipationless to dissipative with increasing
      radiation frequency, signalling a change in the topological properties. The
      connection with Thouless' charge pumping and nonequilibrium zitterbewegung is
      discussed, together with possible experiments.

PMID- 22400949
TI  - Giant Nernst effect and bipolarity in the quasi-one-dimensional metal
      Li0.9Mo6O17.
AB  - The Nernst coefficient for the quasi-one-dimensional metal, Li{0.9}Mo{6}O{17}, is
      found to be among the largest known for metals (nu?500  MUV/KT at T~20  K), and
      is enhanced in a broad range of temperature by orders of magnitude over the value
      expected from Boltzmann theory for carrier diffusion. A comparatively small
      Seebeck coefficient implies that Li{0.9}Mo{6}O{17} is bipolar with large, partial
      Seebeck coefficients of opposite sign. A very large thermomagnetic figure of
      merit, ZT~0.5, is found at high field in the range T~35-50  K.

PMID- 22400951
TI  - Electrically tunable quantum anomalous Hall effect in graphene decorated by 5d
      transition-metal adatoms.
AB  - Based on first-principles calculations, we predict that 5d transition metals on
      graphene present a unique class of hybrid systems exhibiting topological
      transport effects that can be manipulated effectively by external electric
      fields. The origin of this phenomenon lies in the exceptional magnetic properties
      and the large spin-orbit interaction of the 5d metals leading to significant
      magnetic moments accompanied with colossal magnetocrystalline anisotropy
      energies. A strong magnetoelectric response is predicted that offers the
      possibility to switch the spontaneous magnetization direction by moderate
      electric fields, enabling an electrically tunable quantum anomalous Hall effect.

PMID- 22400952
TI  - Superconductivity in the doped topological insulator Cu{x}Bi{2}Se{3} under high
      pressure.
AB  - We report a high-pressure single crystal study of the topological superconductor
      Cu{x}Bi{2}Se{3}. Resistivity measurements under pressure show superconductivity
      is depressed smoothly. At the same time the metallic behavior is gradually lost.
      The upper-critical field data B{c2}(T) under pressure collapse onto a universal
      curve. The absence of Pauli limiting and the comparison of B{c2}(T) to a polar
      state function point to spin-triplet superconductivity, but an anisotropic spin
      singlet state cannot be discarded completely.

PMID- 22400953
TI  - Characterization of a two-transmon processor with individual single-shot qubit
      readout.
AB  - We report the characterization of a two-qubit processor implemented with two
      capacitively coupled tunable superconducting qubits of the transmon type, each
      qubit having its own nondestructive single-shot readout. The fixed capacitive
      coupling yields the sqrt[iSWAP] two-qubit gate for a suitable interaction time.
      We reconstruct by state tomography the coherent dynamics of the two-bit register
      as a function of the interaction time, observe a violation of the Bell inequality
      by 22 standard deviations after correcting readout errors, and measure by quantum
      process tomography a gate fidelity of 90%.

PMID- 22400954
TI  - Spin coupling and orbital angular momentum quenching in free iron clusters.
AB  - Magnetic spin and orbital moments of size-selected free iron cluster ions
      Fe{n}{+} (n=3-20) have been determined via x-ray magnetic circular dichroism
      spectroscopy. Iron atoms within the clusters exhibit ferromagnetic coupling
      except for Fe{13}{+}, where the central atom is coupled antiferromagnetically to
      the atoms in the surrounding shell. Even in very small clusters, the orbital
      magnetic moment is strongly quenched and reduced to 5%-25% of its atomic value
      while the spin magnetic moment remains at 60%-90%. This demonstrates that the
      formation of bonds quenches orbital angular momenta in homonuclear iron clusters
      already for coordination numbers much smaller than those of the bulk.

PMID- 22400955
TI  - Ultrafast spin dynamics in multisublattice magnets.
AB  - We propose a general theoretical framework for ultrafast laser-induced spin
      dynamics in multisublattice magnets. We distinguish relaxation of relativistic
      and exchange origin and show that when the former dominates, nonequivalent
      sublattices have distinct dynamics despite their strong exchange coupling. Even
      more interesting, in the exchange dominated regime sublattices can show highly
      counterintuitive transitions between parallel and antiparallel alignment. This
      allows us to explain recent experiments with antiferromagnetically coupled
      sublattices, and predict that such transitions are possible with ferromagnetic
      coupling as well. In addition, we predict that exchange relaxation enhances the
      demagnetization speed of both sublattices only when they are
      antiferromagnetically coupled.

PMID- 22400956
TI  - Magnetoelectric effect in an XY-like spin glass system Ni{x}Mn{1-x}TiO{3}.
AB  - Magnetoelectric (ME) properties were investigated for an XY-like spin glass (SG)
      system, Ni{x}Mn{1-x}TiO{3} with an ilmenite structure. The ME effect is usually
      observed in systems with peculiar couplings between a crystal lattice and a
      magnetic order. Nonetheless, we found an antisymmetric ME effect with nonzero ME
      tensor elements below T{ME}=8-10  K in samples showing SG transitions. At T{ME},
      no specific heat anomaly was observed, suggesting the absence of long-range
      magnetic order. We discuss the origin of the ME effect in the XY-like SG system
      in terms of an alignment of toroidal moments.

PMID- 22400957
TI  - Atomistic spin dynamic method with both damping and moment of inertia effects
      included from first principles.
AB  - We consider spin dynamics for implementation in an atomistic framework and we
      address the feasibility of capturing processes in the femtosecond regime by
      inclusion of moment of inertia. In the spirit of an s-d-like interaction between
      the magnetization and electron spin, we derive a generalized equation of motion
      for the magnetization dynamics in the semiclassical limit, which is nonlocal in
      both space and time. Using this result we retain a generalized Landau-Lifshitz
      Gilbert equation, also including the moment of inertia, and demonstrate how the
      exchange interaction, damping, and moment of inertia, all can be calculated from
      first principles.

PMID- 22400958
TI  - Experimental realization of a spin-1/2 triangular-lattice Heisenberg
      antiferromagnet.
AB  - We report the results of magnetization and specific heat measurements on
      Ba{3}CoSb{2}O{9}, in which the magnetic Co{2+} ion has a fictitious spin 1/2, and
      provide evidence that a spin-1/2 Heisenberg antiferromagnet on a regular
      triangular lattice is actually realized in Ba{3}CoSb{2}O{9}. We found that the
      entire magnetization curve including the one-third quantum magnetization plateau
      is in excellent quantitative agreement with the results of theoretical
      calculations. We also found that Ba{3}CoSb{2}O{9} undergoes a three-step
      transition within a narrow temperature range.

PMID- 22400959
TI  - Spin nematic order in multiple-spin exchange models on the triangular lattice.
AB  - We figure out that the ground state of a multiple-spin exchange model applicable
      to thin films of solid {3}He possesses an octahedral spin nematic order. In the
      presence of a magnetic field, it is deformed into an antiferroquadrupolar order
      in the perpendicular spin plane, in which lattice Z{3} rotational symmetry is
      also broken. Furthermore, this system shows a narrow magnetization plateau at
      half, m/m{sat}=1/2, which resembles recent magnetization measurements [H. Nema et
      al., Phys. Rev. Lett. 102, 075301 (2009)].

PMID- 22400960
TI  - Optically gated resonant emission of single quantum dots.
AB  - We report on the resonant emission in coherently driven single semiconductor
      quantum dots. We demonstrate that an ultraweak nonresonant laser acts as an
      optical gate for the quantum dot resonant response. We show that the gate laser
      suppresses Coulomb blockade at the origin of a resonant emission quenching, and
      that the optically gated quantum dots systematically behave as ideal two-level
      systems in both regimes of coherent and incoherent resonant emission.

PMID- 22400961
TI  - Bloch-wave engineering of quantum dot micropillars for cavity quantum
      electrodynamics experiments.
AB  - We have employed Bloch-wave engineering to realize submicron diameter high
      quality factor GaAs/AlAs micropillars (MPs). The design features a tapered cavity
      in which the fundamental Bloch mode is subject to an adiabatic transition to
      match the Bragg mirror Bloch mode. The resulting reduced scattering loss leads to
      record-high vacuum Rabi splitting of the strong coupling in MPs with modest
      oscillator strength quantum dots. A quality factor of 13, 600 and a splitting of
      85  MUeV with an estimated visibility v of 0.41 are observed for a small mode
      volume MP with a diameter d{c} of 850 nm.

PMID- 22400827
TI  - Search for new phenomena in tt events with large missing transverse momentum in
      proton-proton collisions at sqrt[s] = 7 TeV with the ATLAS detector.
AB  - A search for new phenomena in tt events with large missing transverse momentum in
      proton-proton collisions at a center-of-mass energy of 7 TeV is presented. The
      measurement is based on 1.04 fb(-1) of data collected with the ATLAS detector at
      the LHC. Contributions to this final state may arise from a number of standard
      model extensions. The results are interpreted in terms of a model where new top
      quark partners are pair produced and each decay to an on-shell top (or antitop)
      quark and a long-lived undetected neutral particle. The data are found to be
      consistent with standard model expectations. A limit at 95% confidence level is
      set excluding a cross section times branching ratio of 1.1 pb for a top-partner
      mass of 420 GeV and a neutral particle mass less than 10 GeV. In a model of
      exotic fourth generation quarks, top-partner masses are excluded up to 420 GeV
      and neutral particle masses up to 140 GeV.

PMID- 22400962
TI  - Onsager model for the structure of rigid rods confined on a spherical surface.
AB  - Recent studies have suggested that a monolayer of self-avoiding hard rods
      confined on a spherical surface may display a distribution texture corresponding
      to splay, tennis-ball, rectangle, or cut-and-rotate splay symmetries. We
      investigate the system on the basis of a generalized Onsager model which includes
      both excluded-volume and entropic effects. The numerical solution indicates that
      the splay state, where on average rods line up in parallel to the longitudinal
      lines on the spherical surface, is the only stable state.

PMID- 22400963
TI  - Shocks near jamming.
AB  - Nonlinear sound is an extreme phenomenon typically observed in solids after
      violent explosions. But granular media are different. Right when they jam, these
      fragile and disordered solids exhibit a vanishing rigidity and sound speed, so
      that even tiny mechanical perturbations form supersonic shocks. Here, we perform
      simulations in which two-dimensional jammed granular packings are dynamically
      compressed and demonstrate that the elementary excitations are strongly nonlinear
      shocks, rather than ordinary phonons. We capture the full dependence of the shock
      speed on pressure and impact intensity by a surprisingly simple analytical model.

PMID- 22400966
TI  - Magnetic resonance imaging by synergistic diffusion-diffraction patterns.
AB  - Inferring on the geometry of an object from its frequency spectrum is highly
      appealing since the object could then be imaged noninvasively or from a distance
      (as famously put by Kac, "can one hear the shape of a drum?"). In nuclear
      magnetic resonance of porous systems, the shape of the drum is represented by the
      pore density function that bears all the information on the collective pore
      microstructure. So far, conventional magnetic resonance imaging (MRI) could only
      detect the pore autocorrelation function, which inherently obscures fine details
      on the pore structure. Here, for the first time, we report on a unique imaging
      mechanism arising from synergistic diffusion-diffractions that directly yields
      the pore density function. This mechanism offers substantially higher spatial
      resolution compared to conventional MRI while retaining all fine details on the
      collective pore morphology. Thus, using these unique synergistic diffusion
      diffractions, the "shape of the drum" can be inferred.

PMID- 22400965
TI  - Identifying dynamical bottlenecks of stochastic transitions in biochemical
      networks.
AB  - In biochemical networks, identifying key proteins and protein-protein reactions
      that regulate fluctuation-driven transitions leading to pathological cellular
      function is an important challenge. Using large deviation theory, we develop a
      semianalytical method to determine how changes in protein expression and rate
      parameters of protein-protein reactions influence the rate of such transitions.
      Our formulas agree well with computationally costly direct simulations and are
      consistent with experiments. Our approach reveals qualitative features of key
      reactions that regulate stochastic transitions.

PMID- 22400967
TI  - Fast and accurate modeling of molecular atomization energies with machine
      learning.
AB  - We introduce a machine learning model to predict atomization energies of a
      diverse set of organic molecules, based on nuclear charges and atomic positions
      only. The problem of solving the molecular Schrodinger equation is mapped onto a
      nonlinear statistical regression problem of reduced complexity. Regression models
      are trained on and compared to atomization energies computed with hybrid density
      functional theory. Cross validation over more than seven thousand organic
      molecules yields a mean absolute error of ~10  kcal/mol. Applicability is
      demonstrated for the prediction of molecular atomization potential energy curves.

PMID- 22400964
TI  - Optimal placement of origins for DNA replication.
AB  - DNA replication is an essential process in biology and its timing must be robust
      so that cells can divide properly. Random fluctuations in the formation of
      replication starting points, called origins, and the subsequent activation of
      proteins lead to variations in the replication time. We analyze these stochastic
      properties of DNA and derive the positions of origins corresponding to the
      minimum replication time. We show that under some conditions the minimization of
      replication time leads to the grouping of origins, and relate this to
      experimental data in a number of species showing origin grouping.

PMID- 22400968
TI  - Shape dynamics and rheology of soft elastic particles in a shear flow.
AB  - The shape dynamics of soft, elastic particles in an unbounded simple shear flow
      is investigated theoretically under Stokes flow conditions. Three types of motion
      steady-state, trembling, and tumbling-are predicted, depending on the shear rate,
      elastic shear modulus, and initial particle shape. The steady-state motion is
      found to be always stable. In addition, the existence of a trembling regime is
      documented for the first time in nonvesicle systems, and a complete phase diagram
      is developed. The rheological properties of dilute suspensions of such soft
      particles generally exhibit shear-thinning behavior and can even display negative
      intrinsic viscosity for sufficiently soft particles.

PMID- 22400969
TI  - Online remote monitoring of patients with differentiated thyroid carcinomas and
      neuroendocrine tumors treated with high doses of radionuclides.
AB  - BACKGROUND: Telemedicine could be very useful for patients in remote areas
      experiencing adverse drug reactions or being in need of sophisticated diagnostic
      or therapeutic procedures. The aim of this article is to show the experience of
      our Department of Nuclear Medicine (DNM) in telemonitoring patients with
      differentiated thyroid carcinomas and neuroendocrine tumors. SUBJECTS AND
      METHODS: The DNM at the Clinical Center Kragujevac, Serbia, uses continuous
      remote monitoring of patients' vital functions, including heart rate,
      electrocardiogram, respiration rate, blood pressure, and oxygen saturation, as
      well as video surveillance of the physical isolation area for patients with
      neuroendocrine tumors (NETs) and some patients with differentiated thyroid
      carcinomas (DTCs), during administration of radionuclide therapy and for the days
      following treatment. RESULTS: The DNM used a telemonitoring system for 156
      patients with either DTC or NET who received radionuclide therapy during the last
      3 years. There were 32 interventions on patients in the physical isolation area
      based on changes of the patients' vital functions detected by the telemonitoring
      system. Twenty-five patients (78%) experienced symptoms, whereas the other seven
      patients (22%) were symptomless. A responsible physician intervened with
      treatment of tachycardia (18 cases), hypertension (10 cases), hypotension (2
      cases), ventricular extrasystoles (1 case), and ST-segment depression (1 case).
      After administration of the treatment the health status of the patients was
      normalized. CONCLUSION: From our experience gained over the past 3 years, this
      model of organization and supervision with a telemonitoring system of patients
      receiving radionuclide therapy ensures a high level of safety for the patient,
      with significant reduction of staff costs.

PMID- 22400971
TI  - Soldiers' personal technologies on deployment and at home.
AB  - OBJECTIVE: Personal technologies such as smartphones, computers, and gaming
      devices, are ubiquitous in the civilian world. Consequently they represent ideal
      vehicles for disseminating psychological and other health resources and
      interventions. However, almost nothing is known about personal technology use in
      the U.S. military. We conducted the most comprehensive survey to date of the use,
      availability, and need for personal technologies by U.S. military service
      members. Our survey asked detailed questions about computers and the Internet,
      phones and smartphones, other mobile or portable technologies, gaming devices,
      and TV and video media used during deployment and at permanent duty station or
      home. MATERIALS AND METHODS: We collected data by paper-and-pencil survey in 2010
      and 2011 from 331 active Army service members at a processing and registration
      center in a large military installation in the western United States. Two cohorts
      were surveyed: Soldiers who had previously been deployed to a warzone and
      soldiers who had never been deployed. RESULTS AND CONCLUSION: We measured high
      rates of personal technology use by service members at home across all popular
      electronic media. Soldiers at home essentially resembled civilian consumers in
      their use of popular technologies. Some technologies, including the Internet,
      gaming, and TV, were widespread on deployment. Others, most notably cellphones,
      were more restricted by availability, connectivity, opportunity, and military
      regulation in the warzone. Results will enable researchers and technology
      developers target their efforts on the most promising and popular technologies
      for psychological health in the military.

PMID- 22400970
TI  - Efficacy of telemedicine for stroke: pooled analysis of the Stroke Team Remote
      Evaluation Using a Digital Observation Camera (STRokE DOC) and STRokE DOC Arizona
      telestroke trials.
AB  - BACKGROUND AND PURPOSE: Telemedicine can disseminate vascular neurology expertise
      and optimize recombinant tissue plasminogen activator (rt-PA) use for acute
      ischemic stroke in rural underserved communities. The purpose of this study was
      to prospectively assess whether telemedicine or telephone was superior for
      decision-making. METHODS: The study design is a pooled analysis of two
      identically designed randomized controlled trials conducted in a multistate hub
      and spoke telestroke network setting with acute stroke syndrome patients,
      comparing telemedicine versus telephone-only consultations. From each trial,
      common data elements were pooled to assess, principally, for correctness of
      thrombolysis decision-making. Secondary outcomes included rt-PA use rate, 90-day
      functional outcome, post-thrombolysis intracranial hemorrhage, and data
      completeness. RESULTS: Two hundred seventy-six pooled patients were evaluated.
      Correct thrombolysis eligibility decisions were made more often with telemedicine
      (96% telemedicine, 83% telephone; odds ratio [OR] 4.2; 95% confidence interval
      [CI] 1.69-10.46; p=0.002). Intravenous rt-PA usage was 26% (29% telemedicine, 24%
      telephone; OR 1.27; 95% CI 0.71-2.25; p=0.41). Ninety-day outcomes were not
      different for Barthel Index, modified Rankin Scale, or mortality. There was no
      difference in post-thrombolysis intracranial hemorrhage (8% telemedicine, 6%
      telephone; p>0.999). CONCLUSIONS: This pooled analysis supports the hypothesis
      that stroke telemedicine consultations, compared with telephone-only, result in
      more accurate decision-making. Together with high rt-PA utilization rate, low
      post-rt-PA intracranial hemorrhage rate, and acceptable patient outcome, the
      results confirm that telemedicine is a viable consultative tool for acute stroke.
      The replication of the hub and spoke network infrastructure supports the
      generalizability of telemedicine when used in broader settings.

PMID- 22400972
TI  - Reliability and validity of gait analysis by android-based smartphone.
AB  - Smartphones are very common devices in daily life that have a built-in tri-axial
      accelerometer. Similar to previously developed accelerometers, smartphones can be
      used to assess gait patterns. However, few gait analyses have been performed
      using smartphones, and their reliability and validity have not been evaluated
      yet. The purpose of this study was to evaluate the reliability and validity of a
      smartphone accelerometer. Thirty healthy young adults participated in this study.
      They walked 20 m at their preferred speeds, and their trunk accelerations were
      measured using a smartphone and a tri-axial accelerometer that was secured over
      the L3 spinous process. We developed a gait analysis application and installed it
      in the smartphone to measure the acceleration. After signal processing, we
      calculated the gait parameters of each measurement terminal: peak frequency (PF),
      root mean square (RMS), autocorrelation peak (AC), and coefficient of variance
      (CV) of the acceleration peak intervals. Remarkable consistency was observed in
      the test-retest reliability of all the gait parameter results obtained by the
      smartphone (p<0.001). All the gait parameter results obtained by the smartphone
      showed statistically significant and considerable correlations with the same
      parameter results obtained by the tri-axial accelerometer (PF r=0.99, RMS r=0.89,
      AC r=0.85, CV r=0.82; p<0.01). Our study indicates that the smartphone with gait
      analysis application used in this study has the capacity to quantify gait
      parameters with a degree of accuracy that is comparable to that of the tri-axial
      accelerometer.

PMID- 22400973
TI  - Detection of asymptomatic paroxysmal atrial fibrillation with the trans
      telephonic electrocardiograph system.
AB  - Paroxysmal atrial fibrillation (PAF) carries an equally high annual stroke rate
      as chronic atrial fibrillation (AF). Furthermore, the frequency and duration of
      PAF are thought to be associated with stroke risk. In this pilot study, a trans
      telephonic electrocardiograph (TTE) monitoring system was used to detect
      asymptomatic PAF and to study the relationship between ischemic stroke and the
      frequency of PAF. Between December 2004 and April 2006, 70 patients enrolled in
      the TTE monitoring program. Patients either transmitted electrocardiograms (ECGs)
      daily or upon experiencing cardiac symptoms. Of the 70 patients included, 25 were
      diagnosed with PAF. In total, 11% (855/7,768) of the recordings were diagnosed as
      PAF, yet less than 2% of total calls collected and less than 17% of all the calls
      with PAF were associated with obvious symptoms. Four patients developed five
      ischemic strokes resulting in a calculated annual stroke rate of 0.56%. Patients
      with stroke had more episodes of AF (56.5+/-106.3 versus 6.7+/-85.9, p=0.685) and
      symptomatic AF episodes (9.8+/-17.5 versus 4.9+/-8.1, p=0.381) than the patients
      who did not have a stroke, but the differences were not statistically significant
      because of the low numbers of patients and episodes. Most PAF episodes were
      asymptomatic, and the TTE system could easily detect these episodes. Furthermore,
      these four patients tended to have more episodes of PAF and more symptomatic
      attacks of PAF than patients who did not have a stroke.

PMID- 22400974
TI  - mHealth data security: the need for HIPAA-compliant standardization.
AB  - The rise in the use of mobile devices, such as smartphones, tablet personal
      computers, and wireless medical devices, as well as the wireless networks that
      enable their use, has raised new concerns for data security and integrity.
      Standardized Health Insurance Portability and Accountability Act of 1996 (HIPAA)
      compliant electronic data security that will allow ubiquitous use of mobile
      health technologies is needed. The lack of standardized data security to assure
      privacy, to allow interoperability, and to maximize the full capabilities of
      mobile devices presents a significant barrier to care. The purpose of this
      article is to provide an overview of the issue and to encourage discussion of
      this important topic. Current security needs, standards, limitations, and
      recommendations for how to address this barrier to care are discussed.

PMID- 22400975
TI  - Benign chondroid syringoma of the orbit: a rare cause of exophtalmos.
AB  - Chondroid syringoma (CS) of the orbit is an extremely rare benign neoplasm. To
      the best of our knowledege, this is the second case reported in the english
      literature.We report a case of a 41-year-old woman with orbital CS. This tumor
      developed slowly over 8 years causing indolor, no axil, exophtalmos of the left
      eye. Computed tomography demonstrated an isodense intraorbital tumor with
      homogeneous enhancement without bony erosion. On Magnetic resonance imaging the
      tumor was isointense on T1-weighted imaging, slightly hyper intense on T2
      weighted imaging, and enhanced after Gadolinium administration. The patient was
      operated via left lateral orbitotomy. At surgery the mass was well circumscribed,
      extraconal, very firm and did not invade or adhere to other structures. The tumor
      was removed in toto. The diagnosis was confirmed by histopathological
      examination, the lesion was nodular, and there was differentiation toward the
      adnexal ductal epithelium with chondromyxoid and adipocytic differentiation in
      the stroma. No recurrence was seen with one year follow-up.CS should be included
      in the differential diagnosis of intra-orbital tumors. Complete resection remains
      the best therapeutic option to prevent recurrence. Close followup is recommended
      because malignant transformation, although rare, is possible.

PMID- 22400976
TI  - Structural and energetic effects in the molecular recognition of amino acids by
      18-crown-6.
AB  - Absolute 18-crown-6 (18C6) affinities of five amino acids (AAs) are determined
      using guided ion beam tandem mass spectrometry techniques. The AAs examined in
      this work include glycine (Gly), alanine (Ala), lysine (Lys), histidine (His),
      and arginine (Arg). Theoretical electronic structure calculations are performed
      to determine stable geometries and energetics for neutral and protonated 18C6 and
      the AAs as well as the proton bound complexes comprised of these species,
      (AA)H(+)(18C6). The proton affinities (PAs) of Gly and Ala are lower than the PA
      of 18C6, whereas the PAs of Lys, His, and Arg exceed that of 18C6. Therefore, the
      collision-induced dissociation (CID) behavior of the (AA)H(+)(18C6) complexes
      differs markedly across these systems. CID of the complexes to Gly and Ala
      produces H(+)(18C6) as the dominant and lowest energy pathway. At elevated
      energies, H(+)(AA) was produced in competition with H(+)(18C6) as a result of the
      relatively favorable entropy change in the formation of H(+)(AA). In contrast,
      CID of the complexes to the protonated basic AAs results in the formation of
      H(+)(AA) as the only direct CID product. H(+)(18C6) was not observed, even at
      elevated energies, as a result of unfavorable enthalpy and entropy change
      associated with its formation. Excellent agreement between the measured and
      calculated (AA)H(+)-18C6 bond dissociation energies (BDEs) is found with M06
      theory for all complexes except (His)H(+)(18C6), where theory overestimates the
      strength of binding. In contrast, B3LYP theory significantly underestimates the
      (AA)H(+)-18C6 BDEs in all cases. Among the basic AAs, Lys exhibits the highest
      binding affinity for 18C6, suggesting that the side chains of Lys residues are
      the preferred binding site for 18C6 complexation in peptides and proteins. Gly
      and Ala exhibit greater 18C6 binding affinities than Lys, suggesting that the N
      terminal amino group provides another favorable binding site for 18C6. Trends in
      the 18C6 binding affinities among the five AAs examined here exhibit an inverse
      correlation with the polarizability and proton affinity of the AA. Therefore, the
      ability of the N-terminal amino group to compete for 18C6 complexation is best
      for Gly and should become increasing less favorable as the size of the side chain
      substituent increases.

PMID- 22400977
TI  - Gender-sensitive reporting in medical research.
AB  - Sex and gender differences influence the health and wellbeing of men and women.
      Although studies have drawn attention to observed differences between women and
      men across diseases, remarkably little research has been pursued to
      systematically investigate these underlying sex differences. Women continue to be
      underrepresented in clinical trials, and even in studies in which both men and
      women participate, systematic analysis of data to identify potential sex-based
      differences is lacking. Standards for reporting of clinical trials have been
      established to ensure provision of complete, transparent and critical
      information. An important step in addressing the gender imbalance would be
      inclusion of a gender perspective in the next Consolidated Standards of Reporting
      Trials (CONSORT) guideline revision. Uniform Requirements for Manuscripts
      Submitted to Biomedical Journals, as a set of well-recognized and widely used
      guidelines for authors and biomedical journals, should similarly emphasize the
      ethical obligation of authors to present data analyzed by gender as a matter of
      routine. Journal editors are also promoters of ethical research and adequate
      standards of reporting, and requirements for inclusion of gender analyses should
      be integrated into editorial policies as a matter of urgency.

PMID- 22400978
TI  - Integration of a nationally procured electronic health record system into user
      work practices.
AB  - BACKGROUND: Evidence suggests that many small- and medium-scale Electronic Health
      Record (EHR) implementations encounter problems, these often stemming from users'
      difficulties in accommodating the new technology into their work practices. There
      is the possibility that these challenges may be exacerbated in the context of the
      larger-scale, more standardised, implementation strategies now being pursued as
      part of major national modernisation initiatives. We sought to understand how
      England's centrally procured and delivered EHR software was integrated within the
      work practices of users in selected secondary and specialist care settings.
      METHODS: We conducted a qualitative longitudinal case study-based investigation
      drawing on sociotechnical theory in three purposefully selected sites
      implementing early functionality of a nationally procured EHR system. The
      complete dataset comprised semi-structured interview data from a total of 66
      different participants, 38.5 hours of non-participant observation of use of the
      software in context, accompanying researcher field notes, and hospital documents
      (including project initiation and lessons learnt reports). Transcribed data were
      analysed thematically using a combination of deductive and inductive approaches,
      and drawing on NVivo8 software to facilitate coding. RESULTS: The nationally led
      "top-down" implementation and the associated focus on interoperability limited
      the opportunity to customise software to local needs. Lack of system usability
      led users to employ a range of workarounds unanticipated by management to
      compensate for the perceived shortcomings of the system. These had a number of
      knock-on effects relating to the nature of collaborative work, patterns of
      communication, the timeliness and availability of records (including paper) and
      the ability for hospital management to monitor organisational performance.
      CONCLUSIONS: This work has highlighted the importance of addressing potentially
      adverse unintended consequences of workarounds associated with the introduction
      of EHRs. This can be achieved with customisation, which is inevitably somewhat
      restricted in the context of attempts to implement national solutions. The
      tensions and potential trade-offs between achieving large-scale interoperability
      and local requirements is likely to be the subject of continuous debate in
      England and beyond with no easy answers in sight.

PMID- 22400979
TI  - Current investigational drugs in psoriasis.
AB  - INTRODUCTION: The advent of biologic therapies has revolutionized the treatment
      of psoriasis. Increased understanding of immunogenetic pathways has allowed for
      the development of more selective targeted biologic therapies. Multiple new
      treatments are currently in development for the treatment of psoriasis.
      Preliminary data for many of these agents, particularly with regard to agents
      targeting the IL-23/Th17 pathway, are promising. Proven long-term safety,
      however, is an absolute necessity with newly developed drugs, and should,
      therefore, still be considered second-line agents to current established
      treatments with long-term safety data. AREAS COVERED: This review details the
      mechanisms of action of drugs currently in development or in clinical trials for
      the treatment of psoriasis, using clinical trial registries and associated
      publications. Readers will gain a comprehensive overview about the mechanism of
      action of emerging treatments targeting various immune pathways deeply involved
      in psoriasis. Pathogenesis, clinical efficacy and safety data for these
      treatments are discussed where available. EXPERT OPINION: Psoriasis remains a
      heavily undertreated systemic immune-mediated disease despite increased
      understanding of immunopathogenesis of the disease and advent of a multitude of
      novel therapeutic agents with potentially improved bioavailability and safety
      profiles. Limitations, however, remain in the realm of topical agents for
      treatment of mild to moderate psoriasis, which has seen little progress over the
      years. A concerted effort will need to be made among researchers, clinicians and
      patient advocacy groups to ensure new therapeutic agents are developed and gain
      proper exposure.

PMID- 22400980
TI  - Construction of polycyclic spiro-indolines via an intramolecular oxidative
      coupling/cyclization cascade reaction process.
AB  - An efficient protocol for assembling a polycyclic spiroindoline scaffold is
      developed, which involves an intramolecular oxidative coupling of dianions
      derived from indole-embodied beta-ketoamides using iodine as the oxidant, and
      subsequent attack of oxygen anion to the resultant imine moiety. A number of
      tetracyclic spiroindolines are prepared with moderate to good yields.

PMID- 22400981
TI  - Mitochondrial DNA mutation m.10680G > A is associated with Leber hereditary optic
      neuropathy in Chinese patients.
AB  - BACKGROUND: Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder
      with gender biased and incomplete penetrance. The majority of LHON patients are
      caused by one of the three primary mutations (m.3460G > A, m.11778G > A and
      m.14484T > C). Rare pathogenic mutations have been occasionally reported in LHON
      patients. METHODS: We screened mutation m.10680G > A in the MT-ND4L gene in 774
      Chinese patients with clinical features of LHON but lacked the three primary
      mutations by using allele specific PCR (AS-PCR). Patients with m.10680G > A were
      further determined entire mtDNA genome sequence. RESULTS: The optimal AS-PCR
      could detect as low as 10% heteroplasmy of mutation m.10680G > A. Two patients
      (Le1263 and Le1330) were identified to harbor m.10680G > A. Analysis of the
      complete mtDNA sequences of the probands suggested that they belonged to
      haplogroups B4a1 and D6a1. There was no other potentially pathogenic mutation,
      except for a few private yet reported variants in the MT-ND1 and MT-ND5 genes, in
      the two lineages. A search in reported mtDNA genome data set (n = 9277; excluding
      Chinese LHON patients) identified no individual with m.10680G > A. Frequency of
      m.10680G > A in Chinese LHON patients analyzed in this study and our previous
      studies (3/784) was significantly higher than that of the general populations
      (0/9277) (P = 0.0005). CONCLUSION: Taken together, we speculated that m.10680G >
      A may be a rare pathogenic mutation for LHON in Chinese. This mutation should be
      included in future clinical diagnosis.

PMID- 22400982
TI  - Deterioration of Parkinson's disease during hospitalization: survey of 684
      patients.
AB  - BACKGROUND: A substantial fraction of Parkinson's disease patients deteriorate
      during hospitalisation, but the precise proportion and the reasons why have not
      been studied systematically and the focus has been on surgical wards and on
      Accident & Emergency departments. We assessed the prevalence and risk factors of
      deterioration of Parkinson's disease symptoms during hospitalization, including
      all wards. METHODS: We invited Parkinson's disease patients from three neurology
      departments in The Netherlands to answer a standardised questionnaire on general,
      disease and hospital related issues. Patients who had been hospitalized in the
      previous year were included and analysed. Possible risk factors for Parkinson's
      disease deterioration were identified. Proportions were analysed using the Chi
      Square test and a logistic regression analysis was performed. RESULTS: Eighteen
      percent of 684 Parkinson's disease patients had been hospitalized at least once
      in the last year. Twenty-one percent experienced deterioration of motor symptoms,
      33% did have one or more complications and 26% had received incorrect anti
      Parkinson's medication. There were no statistically significant differences for
      these variables between admissions on neurologic or non-neurologic wards and
      between having surgery or not. Incorrect medication during hospitalization was
      significantly associated with higher risk (OR 5.8, CI 2.5-13.7) of deterioration,
      as were having infections (OR 6.7 CI 1.8-24.7). A higher levodopa equivalent dose
      per day was a significant risk factor for deterioration. When adjusting for
      different variables, wrong medication distribution was the most important risk
      factor for deterioration. CONCLUSIONS: Incorrect medication and infections are
      the important risk factors for deterioration of Parkinson's disease patients both
      for admissions with and without surgery and both for admissions on neurologic and
      non-neurologic wards. Measures should be taken to improve care and incorporated
      in guidelines.

PMID- 22400983
TI  - High prevalence of Pneumocystis jirovecii colonization among patients with
      autoimmune inflammatory diseases and corticosteroid therapy.
AB  - BACKGROUND: Patients with autoimmune inflammatory diseases (AID) account for 13
      36% of Pneumocystis pneumonia (PCP) cases in human immunodeficiency virus (HIV)
      negative patients. Up to 88% of PCP cases in HIV-negative patients are associated
      with prior steroid treatment. Pulmonary colonization with Pneumocystis in HIV
      negative patients is associated with corticosteroid therapy in up to 75% of
      cases. The aim of this study was to detect the prevalence and risk factors of
      pulmonary colonization with Pneumocystis jirovecii in patients with AID receiving
      corticosteroid therapy in comparison with healthy control persons. METHODS: We
      investigated induced sputa of 102 patients with AID on current corticosteroid
      treatment and of 117 healthy controls for the presence of P. jirovecii using
      polymerase chain reaction (PCR). RESULTS: Twenty-nine patients (28.5%) with AID
      were colonized with P. jirovecii compared to three healthy controls (2.6%) [p <
      0.001, odds ratio (OR) 15.10, 95% confidence interval (CI) 4.43-51.38]. In
      patients with AID, age over 60 years was significantly associated with
      colonization (p = 0.015, OR 3.19, 95% CI 1.27-7.94). Multivariate analysis showed
      age to be independently associated with the colonization of P. jirovecii (95% CI
      1.002-1.092). Neither duration nor dose of corticosteroid therapy nor
      immunosuppressive co-medication had a significant influence on P. jirovecii
      colonization. CONCLUSION: Patients with AID, especially those over 60 years of
      age, display a high prevalence of colonization with P. jirovecii. Clinicians
      should be aware of this and ensure that they consider the possibility of PCP when
      pulmonary symptoms arise in these patients.

PMID- 22400984
TI  - Unusual regression of severe recurrent lymphatic malformation of a face after
      contraception and pregnancy.
AB  - We report the case of a female who had suffered from progressive lymphatic
      malformation in the orbito-temporal region since childhood. Many surgical
      interventions were performed, including radical excision and shunt drainage.
      Despite aggressive surgical treatment, recurrence was observed after every
      intervention. Eventually, the condition regressed after the patient began taking
      a contraceptive. Moreover, it virtually disappeared after pregnancy.

PMID- 22400985
TI  - Transgenic milk containing recombinant human lactoferrin modulates the intestinal
      flora in piglets.
AB  - Lactoferrin (LF) is a beneficial multifunctional protein in milk. The objective
      of this study was to determine whether bovine transgenic milk containing
      recombinant human lactoferrin (rhLF) can modulate intestinal flora in the
      neonatal pig as an animal model for the human infant. We fed 7-day-old piglets
      (i) ordinary whole milk (OM), (ii) a 1:1 mixture of OM and rhLF milk (MM), or
      (iii) rhLF milk (LFM). LFM provided better average daily mass gain than OM (P =
      0.007). PCR-denaturing gradient gel electrophoresis and 16S rDNA sequencing
      analysis revealed that the LFM piglets exhibited more diversity of the intestinal
      flora than the OM group. Except for the colon in the LFM group, an increasing
      trend in microbial diversity occurred from the duodenum to the colon. Fecal flora
      was not different across different ages or different treatment groups, but a
      cluster analysis showed that the fecal flora of OM- and MM-fed piglets had a
      higher degree of similarity than that of LFM-fed piglets. Based on culture-based
      bacterial counts of intestinal content samples, concentrations of Salmonella spp.
      in the colon and of Escherichia coli throughout the intestine were reduced with
      LFM (P < 0.01). Concentrations of Bifidobacterium spp. in the ileum and of
      Lactobacillus spp. throughout the intestine were also increased with LFM (P <=
      0.01). We suggest that rhLF can modulate the intestinal flora in piglets.

PMID- 22400986
TI  - The in vitro toxicology of Swedish snus.
AB  - Three commercial brands of Swedish snus (SWS), an experimental SWS, and the 2S3
      reference moist snuff were each tested in four in vitro toxicology assays. These
      assays were: Salmonella reverse mutation, mouse lymphoma, in vitro micronucleus,
      and cytotoxicity. Water extractions of each of the 5 products were tested using
      several different concentrations; the experimental SWS was also extracted using
      dimethyl sulfoxide (DMSO). Extraction procedures were verified by nicotine
      determinations. Results for SWS in the mutagenicity assays were broadly negative:
      there were occasional positive responses, but these were effectively at the
      highest concentration only (concentrations well above those suggested by
      regulatory guidelines), and were often associated with cytotoxicity. The 2S3
      reference was unequivocally positive in one of the three conditions of the
      micronucleus assay (MNA), at the highest concentration only. Positive controls
      produced the expected responses in each assay. The SWS data are contrasted with
      data reported for combusted tobacco in the form of cigarettes, where strongly
      positive responses have been routinely reported for mutagenicity and
      cytotoxicity. These negative findings in a laboratory setting concur with the
      large amount of epidemiological data from Sweden, data showing that SWS are
      associated with considerably lower carcinogenic potential when compared with
      cigarettes.

PMID- 22400987
TI  - Effect of chitosan, O-carboxymethyl chitosan, and N-[(2-hydroxy-3-N,N
      dimethylhexadecyl ammonium)propyl] chitosan chloride on overweight and insulin
      resistance in a murine diet-induced obesity.
AB  - Two water-soluble chitosan derivatives, O-carboxymethyl chitosan (O-CM-chitosan)
      and N-[(2-hydroxy-3-N,N-dimethylhexadecyl ammonium)propyl] chitosan chloride (N
      CQ-chitosan), were prepared, and the therapeutic effects of chitosan, O-CM
      chitosan, and N-CQ-chitosan on insulin resistance were simultaneously evaluated
      by rats fed on a high-fat diet. The parameters of high-fat diet-induced rats
      indicated that chitosan and its two derivatives not only have low cytotoxicity
      but can control overnutrition by fat and achieve insulin resistance therapy.
      However, the results in experiment in vivo showed that the therapeutic degree
      varied by the molecular weight and surface charge of chitosan, O-CM-chitosan, and
      N-CQ-chitosan. N-CQ-chitosan with a MW of 5 * 10(4) decreased body weight, the
      ratio of fat to body weight, triglyceride, fasting plasma glucose, fasting plasma
      insulin, free fatty acid, and leptin by 11, 17, 44, 46, 44, 87, and 64% and
      increased fecal lipid by 95%, respectively.

PMID- 22400990
TI  - Adsorption of sulfur dioxide by CoFe2O4 spinel ferrite nanoparticles and
      corresponding changes in magnetism.
AB  - Adsorption of sulfur dioxide on 10 nm CoFe(2)O(4) spinel ferrite nanoparticles
      was examined. Adsorption loadings of sulfur dioxide at breakthrough conditions
      were determined to be approximately 0.62 mol/kg, which is significant given the
      150 m(2)/g surface area of the nanoparticles. Adsorption proceeds through a
      chemisorption mechanism with sulfur dioxide forming a sulfate upon adsorption on
      the particle surface, which leads to a 23% decrease in the remnant magnetization,
      a 20% decrease in the saturation magnetization, and a 9% decrease in the
      coercivity of the magnetic nanoparticles. Adsorbent materials that provide a
      magnetic signal when adsorption occurs could have broad implications on
      adsorption-based separations.

PMID- 22400988
TI  - Generation of phosphorescent triplet states via photoinduced electron transfer:
      energy and electron transfer dynamics in Pt porphyrin-Rhodamine B dyads.
AB  - Control over generation and dynamics of excited electronic states is fundamental
      to their utilization in all areas of technology. We present the first example of
      multichromophoric systems in which emissive triplet states are generated via a
      pathway involving photoinduced electron transfer (ET), as opposed to local
      intrachromophoric processes. In model dyads, PtP-Ph(n)-pRhB(+) (1-3, n = 1-3),
      comprising platinum(II) meso-tetraarylporphyrin (PtP) and Rhodamine B piperazine
      derivative (pRhB(+)), linked by oligo-p-phenylene bridges (Ph(n)), upon selective
      excitation of pRhB(+) at a frequency below that of the lowest allowed transition
      of PtP, room-temperature T(1)->S(0) phosphorescence of PtP was observed. The
      pathway leading to the emissive PtP triplet state includes excitation of pRhB(+),
      ET with formation of the singlet radical pair, intersystem crossing within that
      pair, and subsequent radical recombination. Because of the close proximity of the
      triplet energy levels of PtP and pRhB(+), reversible triplet-triplet (TT) energy
      transfer between these states was observed in dyads 1 and 2. As a result, the
      phosphorescence of PtP was extended in time by the long decay of the pRhB(+)
      triplet. Observation of ET and TT in the same series of molecules enabled direct
      comparison of the distance attenuation factors beta between these two closely
      related processes.

PMID- 22400989
TI  - ACTIVE cognitive training and rates of incident dementia.
AB  - Systematic cognitive training produces long-term improvement in cognitive
      function and less difficulty in performing activities of daily living. We
      examined whether cognitive training was associated with reduced rate of incident
      dementia. Participants were from the Advanced Cognitive Training for Independent
      and Vital Elderly (ACTIVE) study (n = 2,802). Incident dementia was defined using
      a combination of interview- and performance-based methods. Survival analysis was
      used to determine if ACTIVE treatment affected the rate of incident dementia
      during 5 years of follow-up. A total of 189 participants met criteria for
      incident dementia. Baseline factors predictive of incident dementia were older
      age, male gender, African American race, fewer years of education, relationship
      other than married, no alcohol use, worse MMSE, worse SF-36 physical functioning,
      higher depressive symptomatology, diabetes, and stroke (all p < .05). A
      multivariable model with significant predictors of incident dementia and training
      group revealed that cognitive training was not associated with a lower rate of
      incident dementia. Cognitive training did not affect rates of incident dementia
      after 5 years of follow-up. Longer follow-up or enhanced training may be needed
      to fully explore the preventive capacity of cognitive training in forestalling
      onset of dementia.

PMID- 22400991
TI  - In vivo activity and duration of short interfering RNAs containing a synthetic 5'
      phosphate.
AB  - Endogenous and exogenous short interfering RNAs (siRNAs) require a 5'-phosphate
      for loading into Ago2 and cleavage of the target mRNA. We applied a synthetic 5'
      phosphate to siRNA guide strands to evaluate if phosphorylation in vivo is rate
      limiting for maximal siRNA knockdown and duration. We report, for the first time,
      an in vivo evaluation of siRNAs with a synthetic 5'-phosphate compared to their
      unphosphorylated versions. siRNAs that contained a 5'-phosphate had the same
      activity in vivo compared with unphosphorylated siRNAs, indicating
      phosphorylation of an siRNA is not a rate limiting step in vivo.

PMID- 22400992
TI  - An investigative study into the influence of a commercially available
      carbohydrate-protein-electrolyte beverage on short term repeated exercise
      performance.
AB  - BACKGROUND: The purpose of this study was to undertake an independent
      investigation into the effects of ingesting a carbohydrate-protein-electrolyte
      (CPE) beverage on repeated submaximal and time-trial cycling performance.
      METHODS: Sixteen recreationally trained males (height: 1.76 +/- 0.07 m; weight:
      70.05 +/- 7.90 kg; VO2max: 49.69 +/- 4.19 ml.kg-1.min-1) performed two exercise
      trials separated by 7 days. Each trial comprised two bouts of 90 minutes exercise
      separated by a 2 hour recovery period. Each bout comprised 45 minutes exercise on
      a cycle-ergometer at 60%VO2max (ST), followed immediately by a 45 minute
      performance test (PT). Participants were randomly assigned an 8% CPE beverage or
      colour/taste matched placebo (PL) prior to each trial. Participants consumed 100
      ml of the assigned beverage every 10 minutes during each ST, and 500 ml at 0 and
      60 minutes into recovery (total caloric delivery per trial: 617.6 kcal for CPE
      and12.8 kcal for PL). Mean power output (W), speed (km.hr-1) and distance covered
      (km) were assessed throughout both trials. Expired air was sampled at 10 minute
      intervals throughout ST. Blood glucose and lactate were assessed during ST and
      recovery. RESULTS: Distance covered during ST was significantly reduced with PL
      by 9.12% (20.18 +/- 0.28 km in ST1 v 18.34 +/- 0.36 km in ST2; P = 0.0001). With
      CPE, distance covered, power output and average speed were maintained between ST1
      and ST2. Oxygen uptake was not significantly different between ST1 and ST2, or
      conditions. Respiratory exchange ratio (RER) values decreased from 0.98 +/- 0.02
      in ST1 to 0.91 +/- 0.02 in ST2 for PL (P = 0.003), supporting reduced total
      carbohydrate oxidation rates (P = 0.007). Mean blood glucose was maintained in
      CPE across ST trials, and was significantly greater than PL in ST2 (4.77 +/- 0.09
      mmol.L-1 for CPE compared with 4.18 +/- 0.06 mmol.L-1 for PL, P < 0.001). Mean
      distance during PT2 was 2.96 km (or 17.1%) further with CPE than PL (P = 0.003).
      Mean power significantly decreased across PT with PL (134.21 +/- 4.79 W and
      106.90 +/- 3.25 W, respectively; P < 0.04). CONCLUSIONS: The use of a CPE
      beverage improves short-term repeated exercise and subsequent performance
      compared to PL. Higher rates of carbohydrate oxidation, maintenance of plasma
      glucose, and decreased levels of fatigue may be beneficial for secondary bouts of
      performance and faster recovery turnover.

PMID- 22400993
TI  - Water splits epitaxial graphene and intercalates.
AB  - The adsorption and reactions of small molecules, such as water and oxygen, with
      graphene films is an area of active research, as graphene may hold the key to
      unique applications in electronics, batteries, and other technologies. Since the
      graphene films produced so far are typically polycrystalline, with point and line
      defects that can strongly affect gas adsorption, there is a need to understand
      their reactivity with environmentally abundant molecules that can adsorb and
      alter their properties. Here we report a study of the adsorption and reactions of
      water, oxygen, hydrogen, and ammonia on epitaxial graphene grown on Ru and Cu
      substrates using scanning tunneling microscopy (STM). We found that on Ru(0001)
      graphene line defects are extremely fragile toward chemical attack by water,
      which splits the graphene film into numerous fragments at temperatures as low as
      90 K, followed by water intercalation under the graphene. On Cu(111) water can
      also split graphene but far less effectively, indicating that the chemical nature
      of the substrate strongly affects the reactivity of the C-C bonds in epitaxial
      graphene. Interestingly, no such effects were observed with other molecules,
      including oxygen, hydrogen, and ammonia also studied here.

PMID- 22400994
TI  - A biochemical marker panel in MRI-proven hyperacute ischemic stroke-a prospective
      study.
AB  - BACKGROUND: Computer tomography (CT) is still the fastest and most robust
      technique to rule out ICH in acute stroke. However CT-sensitivity for detection
      of ischemic stroke in the hyperacute phase is still relatively low. Moreover the
      validity of pure clinical judgment is diminished by several stroke imitating
      diseases (mimics). The "Triage(r) Stroke Panel", a biochemical multimarker assay,
      detects Brain Natriuretic Peptide (BNP), D-Dimers (DD), Matrix-Metalloproteinase
      9 (MMP-9), and S100B protein and promptly generates a Multimarkerindex of these
      values (MMX). This index has been licensed for diagnostic purposes as it might
      increase the validity of the clinical diagnosis to differentiate between stroke
      imitating diseases and true ischemic strokes. Our aim was to prove whether the
      panel is a reliable indicating device for the diagnosis of ischemic stroke in a
      time window of 6 h to fasten the pre- and intrahospital pathway to fibrinolysis.
      METHODS: We investigated all consecutive patients admitted to our stroke unit
      during a time period of 5 months. Only patients with clinical investigation,
      blood sample collection and MRI within six hours from symptom onset were
      included. Values of biochemical markers were analyzed according to the results of
      diffusion weighted MR-imaging. In addition MMX-values in ischemic strokes were
      correlated with the TOAST-criteria. For statistical analysis the SAS Analyst
      software was used. Correlation coefficients were analyzed and comparison tests
      for two or more groups were performed. Statistical significance was assumed in
      case of p < 0.05. Finally a ROC-analysis was performed for the MMX-Index.
      RESULTS: In total 174 patients were included into this study (n = 100 strokes, n
      = 49 mimics, n = 25 transitoric ischemic attacks). In patients with ischemic
      strokes the mean NIHSS was 7.6 +/- 6.2, while the mean DWI-lesion volume was 20.6
      ml (range 186.9 to 4.2 ml). According to the MMX or the individual markers there
      was no statistically significant difference between the group of ischemic strokes
      and the group of mimics. Moreover the correlation of the index and the DWI-lesion
      volume was poor (p = 0.2). CONCLUSIONS: In our setting of acute MRI-proven
      ischemic stroke the used multimarker-assay (Triage(r) Stroke Panel) was not of
      diagnostic validity. We do not recommend to perform this assay as this might lead
      to a unjustified time delay.

PMID- 22400995
TI  - Isoobtusilactone A sensitizes human hepatoma Hep G2 cells to TRAIL-induced
      apoptosis via ROS and CHOP-mediated up-regulation of DR5.
AB  - Hepatoma cells are relatively resistant to TRAIL. We have previously shown that
      isoobtusilactone A (IOA), a potent anticancer agent isolated from Cinnamomum
      kotoense, induced mitochondria-mediated apoptosis in hepatoma cells. Here, we
      report that IOA could potentiate TRAIL-induced apoptosis in Hep G2 cells. The
      combined treatment with IOA and TRAIL significantly induced caspase-dependent
      apoptosis. This correlated with the up-regulation of C/EBP homologous protein
      (CHOP) and death receptor 5 (DR5) protein levels. Gene silencing of the DR5 by
      small interfering RNA abrogated the apoptosis induced by the combined regimen of
      IOA and TRAIL, suggesting that the sensitization to TRAIL was mediated through
      DR5. By analyzing the DR5 promoter, we found that IOA induced a CHOP-dependent
      DR5 transactivation. DR5 expression after IOA treatment was accompanied by
      provoking intracellular reactive oxygen species (ROS) generation. Pretreatment
      with N-acetyl-L-cysteine (NAC) attenuated IOA-induced CHOP and DR5 expression and
      inhibited TRAIL-induced apoptosis. Taken together, our data suggested that ROS
      dependent and CHOP-regulated DR5 expression played a pivotal role in the
      synergistic enhancement of TRAIL-induced apoptosis instigated by IOA in Hep G2
      cells.

PMID- 22400997
TI  - Syn-selective vinylogous Kobayashi aldol reaction.
AB  - The Kobayashi aldol reaction has become a prominent transformation in polyketide
      syntheses. This methodology takes advantage of the directing effects of the Evans
      auxiliary and allows the stereoselective incorporation of a four carbon segment
      with two additional methyl branches establishing an anti-relationship between the
      two newly formed chiral centers. So far this transformation was restricted to
      anti-aldol products. We present here a modified protocol that provides the
      corresponding aldol product with high syn-selectivity.

PMID- 22400998
TI  - Amperometric titrations.

PMID- 22401001
TI  - Electroanalysis and coulometric analysis.

PMID- 22400999
TI  - Chemical microscopy.

PMID- 22401000
TI  - Chromatography.

PMID- 22401003
TI  - Electron spectroscopy.  1.  Ultraviolet photoexcitation.

PMID- 22401002
TI  - Electron microscopy.

PMID- 22401004
TI  - Electron spectroscopy.  II.  X-ray photoexcitation.

PMID- 22401005
TI  - Electron spin resonance.

PMID- 22401006
TI  - Emission spectrometry.

PMID- 22401007
TI  - Flame spectrometry.

PMID- 22401008
TI  - Fluorometric analysis.

PMID- 22401009
TI  - Functional group analysis.

PMID- 22401010
TI  - Gas chromatography.

PMID- 22401011
TI  - Infrared spectrometry.

PMID- 22401013
TI  - Ion exchange.

PMID- 22401012
TI  - Inroganic analysis.

PMID- 22401014
TI  - Ion selective electrodes, potentiometry, and potentiometric titrations.

PMID- 22401015
TI  - Kinetic aspects of analytical chemistry.

PMID- 22401016
TI  - Light absorption spectrometry.

PMID- 22401017
TI  - Magnetic susceptibility. Instrumentation and applications including lunar
      biotype.

PMID- 22401018
TI  - Mass spectrometry.

PMID- 22401019
TI  - Microwave spectroscopy.

PMID- 22401020
TI  - Moessbauer spectrometry.

PMID- 22401021
TI  - Nuclear magnetic resonance spectrometry.

PMID- 22401022
TI  - Nucleonics.

PMID- 22401023
TI  - Organic elemental analysis.

PMID- 22401024
TI  - Organic polarography.

PMID- 22401025
TI  - Polarographic theory, instrumentation, and methodology.

PMID- 22401026
TI  - Raman spectrometry.

PMID- 22401027
TI  - Statistical and mathematical methods in analytical chemistry.

PMID- 22401028
TI  - Thermal analysis.

PMID- 22401030
TI  - Ultraviolet spectrometry.

PMID- 22401029
TI  - Titrations in nonaqueous solvents.

PMID- 22401031
TI  - Use of enzymes in analytical chemistry.

PMID- 22401032
TI  - X-ray absorption and emission.

PMID- 22401033
TI  - X-ray diffraction.

PMID- 22401035
TI  - Improving integrative searching of systems chemical biology data using semantic
      annotation.
AB  - BACKGROUND: Systems chemical biology and chemogenomics are considered critical,
      integrative disciplines in modern biomedical research, but require data mining of
      large, integrated, heterogeneous datasets from chemistry and biology. We
      previously developed an RDF-based resource called Chem2Bio2RDF that enabled
      querying of such data using the SPARQL query language. Whilst this work has
      proved useful in its own right as one of the first major resources in these
      disciplines, its utility could be greatly improved by the application of an
      ontology for annotation of the nodes and edges in the RDF graph, enabling a much
      richer range of semantic queries to be issued. RESULTS: We developed a
      generalized chemogenomics and systems chemical biology OWL ontology called
      Chem2Bio2OWL that describes the semantics of chemical compounds, drugs, protein
      targets, pathways, genes, diseases and side-effects, and the relationships
      between them. The ontology also includes data provenance. We used it to annotate
      our Chem2Bio2RDF dataset, making it a rich semantic resource. Through a series of
      scientific case studies we demonstrate how this (i) simplifies the process of
      building SPARQL queries, (ii) enables useful new kinds of queries on the data and
      (iii) makes possible intelligent reasoning and semantic graph mining in
      chemogenomics and systems chemical biology. AVAILABILITY: Chem2Bio2OWL is
      available at http://chem2bio2rdf.org/owl. The document is available at
      http://chem2bio2owl.wikispaces.com.

PMID- 22401036
TI  - Experimental H-type and L-type bovine spongiform encephalopathy in cattle:
      observation of two clinical syndromes and diagnostic challenges.
AB  - BACKGROUND: The majority of atypical bovine spongiform encephalopathy (BSE) cases
      so far identified worldwide have been detected by active surveillance.
      Consequently the volume and quality of material available for detailed
      characterisation is very limiting. Here we report on a small transmission study
      of both atypical forms, H- and L-type BSE, in cattle to provide tissue for test
      evaluation and research, and to generate clinical, molecular and pathological
      data in a standardised way to enable more robust comparison of the two variants
      with particular reference to those aspects most relevant to case ascertainment
      and confirmatory diagnosis within existing regulated surveillance programmes.
      RESULTS: Two groups of four cattle, intracerebrally inoculated with L-type or H
      type BSE, all presented with a nervous disease form with some similarities to
      classical BSE, which progressed to a more dull form in one animal from each
      group. Difficulty rising was a consistent feature of both disease forms and not
      seen in two BSE-free, non-inoculated cattle that served as controls. The
      pathology and molecular characteristics were distinct from classical BSE, and
      broadly consistent with published data, but with some variation in the
      pathological characteristics. Both atypical BSE types were readily detectable as
      BSE by current confirmatory methods using the medulla brain region at the obex,
      but making a clear diagnostic distinction between the forms was not consistently
      straightforward in this brain region. Cerebellum proved a more reliable sample
      for discrimination when using immunohistochemistry. CONCLUSIONS: The prominent
      feature of difficulty rising in atypical BSE cases may explain the detection of
      naturally occurring cases in emergency slaughter cattle and fallen stock. Current
      confirmatory diagnostic methods are effective for the detection of such atypical
      cases, but consistently and correctly identifying the variant forms may require
      modifications to the sampling regimes and methods that are currently in use.

PMID- 22401037
TI  - "Workhood"-a useful concept for the analysis of health workers' resources? An
      evaluation from Tanzania.
AB  - BACKGROUND: International debates on improving health system performance and
      quality of care are strongly coined by systems thinking. There is a surprising
      lack of attention to the human (worker) elements. Although the central role of
      health workers within the health system has increasingly been acknowledged, there
      are hardly studies that analyze performance and quality of care from an
      individual perspective. Drawing on livelihood studies in health and sociological
      theory of capitals, this study develops and evaluates the new concept of
      workhood. As an analytical device the concept aims at understanding health
      workers' capacities to access resources (human, financial, physical, social,
      cultural and symbolic capital) and transfer them to the community from an
      individual perspective. METHODS: Case studies were conducted in four Reproductive
      and-Child-Health (RCH) clinics in the Kilombero Valley, south-eastern Tanzania,
      using different qualitative methods such as participant observation, informal
      discussions and in-depth interviews to explore the relevance of the different
      types of workhood resources for effective health service delivery. Health
      workers' ability to access these resources were investigated and factors
      facilitating or constraining access identified. RESULTS: The study showed that
      lack of physical, human, cultural and financial capital constrained health
      workers' capacity to act. In particular, weak health infrastructure and health
      system failures led to the lack of sufficient drug and supply stocks and chronic
      staff shortages at the health facilities. However, health workers' capacity to
      mobilize social, cultural and symbolic capital played a significant role in their
      ability to overcome work related problems. Professional and non-professional
      social relationships were activated in order to access drug stocks and other
      supplies, transport and knowledge. CONCLUSIONS: By evaluating the workhood
      concept this study highlights the importance of understanding health worker
      performance by looking at their resources and capacities. Rather than blaming
      health workers for health system failures, applying a strength-based approach
      offers new insights into health workers' capacities and identifies entry points
      for target actions.

PMID- 22401039
TI  - Exciton supersolidity in hybrid Bose-Fermi systems.
AB  - We investigate the ground states of a Bose-Einstein condensate of indirect
      excitons coupled to an electron gas. We show that in a properly designed system
      the crossing of a roton minimum into the negative energy domain can result in the
      appearance of the supersolid phase, characterized by periodicity in both real and
      reciprocal space. Accounting for the spin-dependent exchange interaction of
      excitons we obtain ferromagnetic supersolid domains. The Fourier spectra of
      excitations of weakly perturbed supersolids show pronounced diffraction maxima
      which may be detected experimentally.

PMID- 22401038
TI  - Lipoprotein-associated phospholipase A2 (Lp-PLA2): a review of its role and
      significance as a cardiovascular biomarker.
AB  - OBJECTIVE: To conduct a comprehensive, systematic review of studies assessing the
      significance of lipoprotein-associated phospholipase A2 in cardiovascular
      diseases (CVDs). MATERIAL AND METHODS: A review of the literature was performed
      using the search term "Lipoprotein-associated phospholipase A2 (Lp-PLA2)" and
      each of the following terms: "cardiovascular risk," "cardiovascular death,"
      "atherosclerotic disease," "coronary events," "transient ischemic attack (TIA),"
      "stroke," and "heart failure." The searches were performed on Medline, Google
      Scholar and ClinicalTrials.gov. RESULTS: The majority of published studies showed
      a significant association between Lp-PLA2 levels and cardiovascular events after
      multivariate adjustment. The association was consistent across a wide variety of
      subjects of both sexes and different ethnic backgrounds. CONCLUSIONS: The role of
      Lp-PLA2 as a significant biomarker of vascular inflammation was confirmed, and Lp
      PLA2 seems to be closely correlated to cardiovascular events. It may be an
      important therapeutic target and may have an important role in prevention, risk
      stratification and personalised medicine.

PMID- 22401041
TI  - Complete set of operational measures for the characterization of three-qubit
      entanglement.
AB  - We characterize the entanglement contained in a pure three-qubit state via
      operational entanglement measures. To this end, we derive a new decomposition for
      arbitrary three-qubit states which is characterized by five parameters (up to
      local unitary operations). We show that these parameters are uniquely determined
      by bipartite entanglement measures. These quantities measure the entanglement
      required to generate the state following a particular preparation procedure and
      have a clear physical meaning. Moreover, we show that the classification of
      states obtained in this way is strongly related to the one obtained when
      considering general local operations and classical communication.

PMID- 22401040
TI  - Clock shift in a strongly interacting two-dimensional Fermi gas.
AB  - We derive universal relations for the rf spectroscopy of a two-dimensional Fermi
      gas consisting of two spin states interacting through an S-wave scattering
      length. The rf transition rate has a high-frequency tail that is proportional to
      the contact and displays logarithmic scaling violations, decreasing
      asymptotically like 1/(omega2ln2omega). Its coefficient is proportional to
      ln2'(a'(2D)/a(2D)), where a(2D) and a'(2D) are the two-dimensional scattering
      lengths associated with initial-state and final-state interactions. The clock
      shift is proportional to the contact and to ln(a'(2D)/a(2D)). If
      |ln(a'(2D)/a(2D))| >> 1, the clock shift arises as a cancellation between much
      larger contributions proportional to ln2(a'(2D)/a(2D)) from bound-bound and bound
      free rf transitions.

PMID- 22401042
TI  - Compact continuous-variable entanglement distillation.
AB  - We introduce a new scheme for continuous-variable entanglement distillation that
      requires only linear temporal and constant physical or spatial resources.
      Distillation is the process by which high-quality entanglement may be distributed
      between distant nodes of a network in the unavoidable presence of decoherence.
      The known versions of this protocol scale exponentially in space and doubly
      exponentially in time. Our optimal scheme therefore provides exponential
      improvements over existing protocols. It uses a fixed-resource module-an
      entanglement distillery-comprising only four quantum memories of at most 50%
      storage efficiency and allowing a feasible experimental implementation. Tangible
      quantum advantages are obtainable by using existing off-resonant Raman quantum
      memories outside their conventional role of storage.

PMID- 22401043
TI  - Generation of a decoherence-free entangled state using a radio-frequency dressed
      state.
AB  - We propose the generation of entangled states with trapped calcium ions using a
      combination of an rf dressed state and a spin-dependent force. By using this
      method, a decoherence-free entangled state of rf qubits can be directly
      generated, and ideally its fidelity is close to unity. We demonstrate an rf
      entangled state with a fidelity of 0.68+/-0.08, which has a coherence time of
      more than 200 ms by virtue of the fact that it is an eigenstate with energy gaps
      between adjacent levels. Using the same technique, we also produce a qutrit
      qutrit entangled state with a fidelity of 0.77+/-0.09, which exceeds the
      threshold value for separability of 2/3.

PMID- 22401044
TI  - Rectification of spatial disorder.
AB  - We demonstrate that a large ensemble of noiseless globally coupled-pinned
      oscillators is capable of rectifying spatial disorder with spontaneous current
      activated through a dynamical phase transition mechanism, either of first or
      second order, depending on the profile of the pinning potential. In the presence
      of an external weak drive, the same collective mechanism can result in an
      absolute negative mobility, which, though not immediately related to symmetry
      breaking, is most prominent at the phase transition. Our results apply to a tug
      of-war by competing molecular motors for bidirectional cargo transport.

PMID- 22401045
TI  - Phase diagram and density large deviations of a nonconserving ABC model.
AB  - The effect of particle-nonconserving processes on the steady state of driven
      diffusive systems is studied within the context of a generalized ABC model. It is
      shown that in the limit of slow nonconserving processes, the large deviation
      function of the overall particle density can be computed by making use of the
      steady-state density profile of the conserving model. In this limit one can
      define a chemical potential and identify first order transitions via Maxwell's
      construction, similarly to what is done in equilibrium systems. This method may
      be applied to other driven models subjected to slow nonconserving dynamics.

PMID- 22401046
TI  - Classical driven transport in open systems with particle interactions and general
      couplings to reservoirs.
AB  - We study nonequilibrium steady states of lattice gases with nearest-neighbor
      interactions that are driven between two reservoirs. Density profiles in these
      systems exhibit oscillations close to the reservoirs. We demonstrate that an
      approach based on time-dependent density functional theory copes with these
      oscillations and predicts phase diagrams of bulk densities to a good
      approximation under arbitrary boundary-reservoir couplings. The minimum or
      maximum current principles can be applied only for specific bulk-adapted
      couplings. We show that they generally fail to give the correct topology of phase
      diagrams but can still be useful for getting insight into the mutual arrangement
      of different phases.

PMID- 22401047
TI  - Infinite invariant density determines statistics of time averages for weak chaos.
AB  - Weakly chaotic nonlinear maps with marginal fixed points have an infinite
      invariant measure. Time averages of integrable and nonintegrable observables
      remain random even in the long time limit. Temporal averages of integrable
      observables are described by the Aaronson-Darling-Kac theorem. We find the
      distribution of time averages of nonintegrable observables, for example, the time
      average position of the particle, x[over -]. We show how this distribution is
      related to the infinite invariant density. We establish four identities between
      amplitude ratios controlling the statistics of the problem.

PMID- 22401048
TI  - Suppression of self-induced flavor conversion in the supernova accretion phase.
AB  - Self-induced flavor conversions of supernova (SN) neutrinos can strongly modify
      the flavor-dependent fluxes. We perform a linearized flavor stability analysis
      with accretion-phase matter profiles of a 15M[symbol: see text] spherically
      symmetric model and corresponding neutrino fluxes. We use realistic energy and
      angle distributions, the latter deviating strongly from quasi-isotropic emission,
      thus accounting for both multiangle and multienergy effects. For our matter and
      neutrino density profile we always find stable conditions: flavor conversions are
      limited to the usual Mikheyev-Smirnov-Wolfenstein effect. In this case one may
      distinguish the neutrino mass hierarchy in a SN neutrino signal if the mixing
      angle theta13 is as large as suggested by recent experiments.

PMID- 22401049
TI  - Entropy generation across Earth's collisionless bow shock.
AB  - Earth's bow shock is a collisionless shock wave but entropy has never been
      directly measured across it. The plasma experiments on Cluster and Double Star
      measure 3D plasma distributions upstream and downstream of the bow shock allowing
      calculation of Boltzmann's entropy function H and his famous H theorem, dH/dt<=0.
      The collisionless Boltzmann (Vlasov) equation predicts that the total entropy
      does not change if the distribution function across the shock becomes nonthermal,
      but it allows changes in the entropy density. Here, we present the first direct
      measurements of entropy density changes across Earth's bow shock and show that
      the results generally support the model of the Vlasov analysis. These
      observations are a starting point for a more sophisticated analysis that includes
      3D computer modeling of collisionless shocks with input from observed particles,
      waves, and turbulences.

PMID- 22401050
TI  - Protoneutron star cooling with convection: the effect of the symmetry energy.
AB  - We model neutrino emission from a newly born neutron star subsequent to a
      supernova explosion to study its sensitivity to the equation of state, neutrino
      opacities, and convective instabilities at high baryon density. We find the time
      period and spatial extent over which convection operates is sensitive to the
      behavior of the nuclear symmetry energy at and above nuclear density. When
      convection ends within the protoneutron star, there is a break in the predicted
      neutrino emission that may be clearly observable.

PMID- 22401051
TI  - Main sequence stars with asymmetric dark matter.
AB  - We study the effects of feebly or nonannihilating weakly interacting dark matter
      (DM) particles on stars that live in DM environments denser than that of our Sun.
      We find that the energy transport mechanism induced by DM particles can produce
      unusual conditions in the cores of main sequence stars, with effects which can
      potentially be used to probe DM properties. We find that solar mass stars placed
      in DM densities of rho(chi)>=10(2) GeV/cm(3) are sensitive to spin-dependent
      scattering cross section sigma(SD)>=10(-37) cm(2) and a DM particle mass as low
      as m(chi)=5 GeV, accessing a parameter range weakly constrained by current direct
      detection experiments.

PMID- 22401052
TI  - Observing Lense-Thirring precession in tidal disruption flares.
AB  - When a star is tidally disrupted by a supermassive black hole (SMBH), the streams
      of liberated gas form an accretion disk after their return to pericenter. We
      demonstrate that Lense-Thirring precession in the spacetime around a rotating
      SMBH can produce significant time evolution of the disk angular momentum vector,
      due to both the periodic precession of the disk and the nonperiodic, differential
      precession of the bound debris streams. Jet precession and periodic modulation of
      disk luminosity are possible consequences. The persistence of the jetted x-ray
      emission in the Swift J164449.3+573451 flare suggests that the jet axis was
      aligned with the spin axis of the SMBH during this event.

PMID- 22401053
TI  - Gravitational particle production in massive chaotic inflation and the moduli
      problem.
AB  - Particle production from vacuum fluctuations during inflation is briefly
      revisited. The moduli problem occurring with light particles produced at the end
      of inflation is addressed, namely, the fact that some results are in disagreement
      with nucleosynthesis constrains. A universal solution to this problem is found
      which leads to reasonable reheating temperatures in all cases. It invokes the
      assumption that, immediately after inflation, the moduli evolve like
      nonrelativistic matter. The assumption is justified in the context of massive
      chaotic inflation where, at the end of inflation, the Universe evolves as if it
      were matter dominated.

PMID- 22401054
TI  - Axion dark matter and cosmological parameters.
AB  - We observe that photon cooling after big bang nucleosynthesis but before
      recombination can remove the conflict between the observed and theoretically
      predicted value of the primordial abundance of ^{7}Li. Such cooling is ordinarily
      difficult to achieve. However, the recent realization that dark matter axions
      form a Bose-Einstein condensate provides a possible mechanism because the much
      colder axions may reach thermal contact with the photons. This proposal predicts
      a high effective number of neutrinos as measured by the cosmic microwave
      anisotropy spectrum.

PMID- 22401055
TI  - Infrared fixed point of the 12-fermion SU(3) gauge model based on 2-lattice Monte
      Carlo renomalization-group matching.
AB  - I investigate an SU(3) gauge model with 12 fundamental fermions. The physically
      interesting region of this strongly coupled system can be influenced by an
      ultraviolet fixed point due to lattice artifacts. I suggest to use a gauge action
      with an additional negative adjoint plaquette term that lessens this problem. I
      also introduce a new analysis method for the 2-lattice matching Monte Carlo
      renormalization group technique that significantly reduces finite volume effects.
      The combination of these two improvements allows me to measure the bare step
      scaling function in a region of the gauge coupling where it is clearly negative,
      indicating a positive renormalization group beta function and infrared
      conformality.

PMID- 22401056
TI  - Nonanalyticity in scale in the planar limit of QCD.
AB  - Using methods of numerical lattice gauge theory we show that, in the limit of a
      large number of colors, properly regularized Wilson loops have an eigenvalue
      distribution which changes nonanalytically as the overall size of the loop is
      increased. This establishes a large-N phase transition in continuum planar gauge
      theory, a fact whose precise implications remain to be worked out.

PMID- 22401057
TI  - Maximal-helicity-violating n-point one-loop amplitude in N=4 supergravity.
AB  - We propose an explicit formula for the n-point maximal-helicity-violating one
      loop amplitude in a N=4 supergravity theory. This formula is derived from the
      soft and collinear factorizations of the amplitude.

PMID- 22401058
TI  - First measurement of the partial widths of 209Bi decay to the ground and to the
      first excited states.
AB  - 209Bi alpha decay to the ground and to the first excited state have been recently
      observed for the first time with a large BGO scintillating bolometer. The half
      life of 209Bi is determined to be tau(1/2)=(2.01+/-0.08)*10(19) yr while the
      branching ratio for the ground-state to ground-state transition is (98.8+/-0.3)%.

PMID- 22401059
TI  - Q value and half-lives for the double-beta-decay nuclide 110Pd.
AB  - The 110Pd double-beta decay Q value was measured with the Penning-trap mass
      spectrometer ISOLTRAP to be Q=2017.85(64) keV. This value shifted by 14 keV
      compared with the literature value and is 17 times more precise, resulting in new
      phase-space factors for the two-neutrino and neutrinoless decay modes. In
      addition a new set of the relevant matrix elements has been calculated. The
      expected half-life of the two-neutrino mode was reevaluated as 1.5(6)*10(20) yr.
      With its high natural abundance, the new results reveal 110Pd to be an excellent
      candidate for double-beta decay studies.

PMID- 22401060
TI  - Evidence for a smooth onset of deformation in the neutron-rich Kr isotopes.
AB  - The neutron-rich nuclei 94,96Kr were studied via projectile Coulomb excitation at
      the REX-ISOLDE facility at CERN. Level energies of the first excited 2(+) states
      and their absolute E2 transition strengths to the ground state are determined and
      discussed in the context of the E(2(1)(+)) and B(E2;2(1)(+)->0(1)(+)) systematics
      of the krypton chain. Contrary to previously published results no sudden onset of
      deformation is observed. This experimental result is supported by a new proton
      neutron interacting boson model calculation based on the constrained Hartree-Fock
      Bogoliubov approach using the microscopic Gogny-D1M energy density functional.

PMID- 22401061
TI  - Experimental determination of in-medium cluster binding energies and Mott points
      in nuclear matter.
AB  - In-medium binding energies and Mott points for d, t, 3He and alpha clusters in
      low-density nuclear matter have been determined at specific combinations of
      temperature and density in low-density nuclear matter produced in collisions of
      47A MeV 40Ar and 64Zn projectiles with 112Sn and 124Sn target nuclei. The
      experimentally derived values of the in-medium modified binding energies are in
      good agreement with recent theoretical predictions based upon the implementation
      of Pauli blocking effects in a quantum statistical approach.

PMID- 22401063
TI  - Subcycle controlled charge-directed reactivity with few-cycle midinfrared pulses.
AB  - The steering of electron motion in molecules is accessible with waveform
      controlled few-cycle laser light and may control the outcome of light-induced
      chemical reactions. An optical cycle of light, however, is much shorter than the
      duration of the fastest dissociation reactions, severely limiting the degree of
      control that can be achieved. To overcome this limitation, we extended the
      control metrology to the midinfrared studying the prototypical dissociative
      ionization of D(2) at 2.1 MUm. Pronounced subcycle control of the directional
      D(+) ion emission from the fragmentation of D(2)(+) is observed, demonstrating
      unprecedented charge-directed reactivity. Two reaction pathways, showing
      directional ion emission, could be observed and controlled simultaneously for the
      first time. Quantum-dynamical calculations elucidate the dissociation channels,
      their observed phase relation, and the control mechanisms.

PMID- 22401062
TI  - Mechanism of delayed double ionization in a strong laser field.
AB  - When intense laser pulses release electrons nonsequentially, the time delay
      between the last recollision and the subsequent ionization may last longer than
      what is expected from a direct impact scenario [recollision excitation with
      subsequent ionization (RESI)]. We show that the resulting delayed ionization
      stems from the inner electron being promoted to a sticky region. We identify the
      mechanism that traps and releases the electron from this region. As a signature
      of this mechanism, we predict oscillations in the ratio of RESI to double
      ionization yields versus laser intensity.

PMID- 22401064
TI  - Effect of cusps in time-dependent quantum mechanics.
AB  - Within nonrelativistic quantum mechanics, spatial cusps in initial wave functions
      can lead to nonanalytic behavior in time. We suggest a method for calculating the
      short-time behavior in such situations. For these cases, the density does not
      match its Taylor expansion in time, but the Runge-Gross proof of time-dependent
      density functional theory still holds, as it requires only the potential to be
      time analytic.

PMID- 22401065
TI  - Driving Rydberg-Rydberg transitions from a coplanar microwave waveguide.
AB  - The coherent interaction between ensembles of helium Rydberg atoms and microwave
      fields in the vicinity of a solid-state coplanar waveguide is reported. Rydberg
      Rydberg transitions, at frequencies between 25 and 38 GHz, have been studied for
      states with principal quantum numbers in the range 30-35 by selective electric
      field ionization. An experimental apparatus cooled to 100 K was used to reduce
      effects of blackbody radiation. Inhomogeneous, stray electric fields emanating
      from the surface of the waveguide have been characterized in frequency- and time
      resolved measurements and coherence times of the Rydberg atoms on the order of
      250 ns have been determined. These results represent a key element in the
      development of an experimental architecture to interface Rydberg atoms with solid
      state devices.

PMID- 22401066
TI  - Nuclear shape effect on the g factor of hydrogenlike ions.
AB  - The nuclear shape correction to the g factor of a bound electron in the 1S state
      is calculated for a number of nuclei in the range of charge numbers from Z=6 up
      to Z=92. The leading relativistic deformation correction has been derived
      analytically, and also its influence on one-loop quantum electrodynamic terms has
      been evaluated. We show the leading corrections to become significant for mid-Z
      ions and for very heavy elements to even reach the 10(-6) level.

PMID- 22401067
TI  - Interference between competing pathways in atomic harmonic generation.
AB  - We investigate the influence of the autoionizing 3s3p(6)nl resonances on the
      fifth harmonic generated by 200-240 nm laser fields interacting with Ar. To
      determine the influence of a multielectron response we develop the capability
      within time-dependent R-matrix theory to determine the harmonic spectra
      generated. The fifth harmonic is affected by interference between the response of
      a 3s electron and the response of a 3p electron, as demonstrated by the
      asymmetric profiles in the harmonic yields as functions of wavelength.

PMID- 22401068
TI  - Angle-resolved electron spectroscopy of laser-assisted Auger decay induced by a
      few-femtosecond x-ray pulse.
AB  - Two-color (x-ray+infrared) electron spectroscopy is used for investigating laser
      assisted KLL Auger decay following 1s photoionization of atomic Ne with few
      femtosecond x-ray pulses from the Linac Coherent Light Source. In an angle
      resolved experiment, the overall width of the laser-modified Auger-electron
      spectrum and its structure change significantly as a function of the emission
      angle. The spectra are characterized by a strong intensity variation of the
      sidebands revealing a gross structure. This variation is caused, as predicted by
      theory, by the interference of electrons emitted at different times within the
      duration of one optical cycle of the infrared dressing laser, which almost
      coincides with the lifetime of the Ne 1s vacancy.

PMID- 22401069
TI  - Surface-electrode Rydberg-Stark decelerator.
AB  - Hydrogen atoms in Rydberg states with principal quantum numbers between 23 and 70
      have been accelerated, decelerated, and electrostatically trapped using a surface
      electrode Rydberg-Stark decelerator. By applying a set of oscillating electrical
      potentials to a two-dimensional array of electrodes on a printed circuit board
      (PCB), a continuously moving, three-dimensional electric trap with a predefined
      velocity and acceleration is generated. From an initial longitudinal velocity of
      760  m/s, final velocities of the Rydberg atoms ranging from 1200  m/s to zero
      velocity in the laboratory-fixed frame of reference were achieved. Accelerated or
      decelerated atoms were detected directly by pulsed electric-field ionization.
      Atoms trapped at zero mean velocity above the PCB were reaccelerated off the PCB
      before field ionization.

PMID- 22401070
TI  - Clocking ultrafast wave packet dynamics in molecules through UV-induced symmetry
      breaking.
AB  - We investigate the use of UV-pump-UV-probe schemes to trace the evolution of
      nuclear wave packets in excited molecular states by analyzing the asymmetry of
      the electron angular distributions resulting from dissociative ionization. The
      asymmetry results from the coherent superposition of gerade and ungerade states
      of the remaining molecular ion in the region where the nuclear wave packet
      launched by the pump pulse in the neutral molecule is located. Hence, the
      variation of this asymmetry with the time delay between the pump and the probe
      pulses parallels that of the moving wave packet and, consequently, can be used to
      clock its field-free evolution. The performance of this method is illustrated for
      the H(2) molecule.

PMID- 22401071
TI  - Experimental estimate of a classicality witness via a single measurement.
AB  - The perception that quantum correlations can still appear in separable states has
      opened exciting new possibilities regarding their use as a resource in quantum
      information science. Quantifying such quantum correlations involves the complete
      knowledge of the system's state and numerical optimization procedures. Thus, it
      is natural to seek methods involving fewer measurements that indicate the nature
      of the correlations in a system. Here we propose a classicality witness that can
      be accurately estimated via statistics from a single measurement and perform an
      experiment to explore the utility of this witness for quantum states with
      different types of correlations.

PMID- 22401072
TI  - Integrability and conservation laws for the nonlinear evolution equations of
      partially coherent waves in noninstantaneous Kerr media.
AB  - It is shown that the evolution equations describing partially coherent wave
      propagation in noninstantaneous Kerr media are integrable and have an infinite
      number of invariants. A recursion relation for generating these invariants is
      presented, and it is demonstrated how to express them in the coherent density,
      self-consistent multimode, mutual coherence, and Wigner formalisms.

PMID- 22401073
TI  - Nonlocal transformation optics.
AB  - We show that the powerful framework of transformation optics may be exploited for
      engineering the nonlocal response of artificial electromagnetic materials.
      Relying on the form-invariant properties of coordinate-transformed Maxwell's
      equations in the spectral domain, we derive the general constitutive "blueprints"
      of transformation media yielding prescribed nonlocal field-manipulation effects
      and provide a physically incisive and powerful geometrical interpretation in
      terms of deformation of the equifrequency contours. In order to illustrate the
      potentials of our approach, we present an example of application to a wave
      splitting refraction scenario, which may be implemented via a simple class of
      artificial materials. Our results provide a systematic and versatile framework
      which may open intriguing venues in dispersion engineering of artificial
      materials.

PMID- 22401074
TI  - Correlations of record events as a test for heavy-tailed distributions.
AB  - A record is an entry in a time series that is larger or smaller than all previous
      entries. If the time series consists of independent, identically distributed
      random variables with a superimposed linear trend, record events are positively
      (negatively) correlated when the tail of the distribution is heavier (lighter)
      than exponential. Here we use these correlations to detect heavy-tailed behavior
      in small sets of independent random variables. The method consists of converting
      random subsets of the data into time series with a tunable linear drift and
      computing the resulting record correlations.

PMID- 22401075
TI  - Destruction of adiabatic invariance for billiards in a strong nonuniform magnetic
      field.
AB  - We study a classical billiard of charged particles in a strong nonuniform
      magnetic field. We provide an adiabatic description for skipping motion along the
      boundary of the billiard. We show that a sequence of many changes of regimes of
      motion from skipping to motion without collisions with the boundary and back to
      skipping leads to destruction of the adiabatic invariance and chaotic dynamics in
      a large domain in the phase space. This is a new mechanism of the origin of
      chaotic dynamics for systems with impacts.

PMID- 22401076
TI  - Dynamical coupling between gradients and transport in fusion plasmas.
AB  - The dynamical coupling between density gradients and particle transport has been
      investigated using similar experimental tools in the plasma boundary of different
      tokamak (JET, ISTTOK) and stellarator (TJ-II) devices, showing that the size of
      turbulent events is minimum in the proximity of the most probable density
      gradient. Experimental results were found to be consistent with results from two
      very different models of plasma turbulence and transport. The present findings,
      common to several plasma devices, suggest the importance of self-regulation
      mechanisms between plasma transport and gradients in fusion devices.

PMID- 22401077
TI  - Transport-driven toroidal rotation in the tokamak edge.
AB  - The interaction of passing-ion drift orbits with spatially inhomogeneous but
      purely diffusive radial transport is demonstrated to cause spontaneous toroidal
      spin-up in a simple model of the tokamak edge. Physically, major-radial orbit
      shifts cause orbit-averaged diffusivities to depend on v(?), including its sign,
      leading to residual stress. The resulting pedestal-top intrinsic rotation scales
      with T(i)/B(theta), resembling typical experimental scalings. Additionally, an
      inboard (outboard) X point enhances co- (counter)current rotation.

PMID- 22401078
TI  - Electronic detection of collective modes of an ultracold plasma.
AB  - Using a new technique to directly detect current induced on a nearby electrode,
      we measure plasma oscillations in ultracold plasmas, which are influenced by the
      inhomogeneous and time-varying density and changing neutrality. Electronic
      detection avoids heating and evaporation dynamics associated with previous
      measurements and allows us to test the importance of the plasma neutrality. We
      apply dc and pulsed electric fields to control the electron loss rate and find
      that the charge imbalance of the plasma has a significant effect on the resonant
      frequency, in excellent agreement with recent predictions suggesting coupling to
      an edge mode.

PMID- 22401079
TI  - Bow shock formation in a complex plasma.
AB  - A bow shock is observed in a two-dimensional supersonic flow of charged
      microparticles in a complex plasma. A thin conducting needle is used to make a
      potential barrier as an obstacle for the particle flow in the complex plasma. The
      flow is generated and the flow velocity is controlled by changing a tilt angle of
      the device under the gravitational force. A void, microparticle-free region, is
      formed around the potential barrier surrounding the obstacle. The flow is bent
      around the leading edge of the void and forms an arcuate structure when the flow
      is supersonic. The structure is characterized by the bow shock as confirmed by a
      polytropic hydrodynamic theory as well as numerical simulation.

PMID- 22401080
TI  - Convective cells and blob control in a simple magnetized plasma.
AB  - Blob control by creating convective cells using biased electrodes is demonstrated
      in simple magnetized toroidal plasmas. A two-dimensional array of electrodes is
      installed on a metal limiter to obtain different biasing schemes. Detailed two
      dimensional measurements across the magnetic field reveal the formation of a
      convective cell, which shows a high degree of uniformity along the magnetic
      field. Depending on the biasing scheme, radial and vertical blob velocities can
      be varied significantly. A high level of cross-field currents limits the
      achievable potential variations to values well below the applied bias voltage.
      Furthermore, the strongest potential variations are not induced along the biased
      flux tube, but at a position shifted in the direction of plasma flows.

PMID- 22401081
TI  - Frictionless flow in a binary polariton superfluid.
AB  - We study the properties of a binary microcavity polariton superfluid coherently
      injected by two lasers at different momenta and energies. The crossover from the
      supersonic to the subsonic regime, where motion is frictionless, is described by
      evaluating the linear response of the system to a weak defect potential. We show
      that the coupling between the two components requires that either both components
      flow without friction or both scatter against the defect, though scattering can
      be small when the two fluids are weakly coupled. By analyzing the drag force
      exerted on a defect, we give a recipe to experimentally address the crossover
      from the supersonic to the subsonic regime.

PMID- 22401082
TI  - Quantum memory assisted probing of dynamical spin correlations.
AB  - We propose a method to probe time-dependent correlations of nontrivial
      observables in many-body ultracold lattice gases. The scheme uses a quantum
      nondemolition matter-light interface, first to map the observable of interest on
      the many-body system into the light and then to store coherently such information
      into an external system acting as a quantum memory. Correlations of the
      observable at two (or more) instances of time are retrieved with a single final
      measurement that includes the readout of the quantum memory. Such a method brings
      to reach the study of dynamics of many-body systems in and out of equilibrium by
      means of quantum memories in the field of quantum simulators.

PMID- 22401083
TI  - Crystal structure of cold compressed graphite.
AB  - Through a systematic structural search we found an allotrope of carbon with Cmmm
      symmetry which we predict to be more stable than graphite for pressures above 10
      GPa. This material, which we refer to as Z-carbon, is formed by pure sp(3) bonds
      and it provides an explanation to several features in experimental x-ray
      diffraction and Raman spectra of graphite under pressure. The transition from
      graphite to Z-carbon can occur through simple sliding and buckling of graphene
      sheets. Our calculations predict that Z-carbon is a transparent wide band-gap
      semiconductor with a hardness comparable to diamond.

PMID- 22401084
TI  - Morphology of lamellae-forming block copolymer films between two orthogonal
      chemically nanopatterned striped surfaces.
AB  - The structure of block copolymers results from the interplay between weak
      intermolecular forces, typically in the order of k(B)T per molecule. This is
      particularly true for block copolymer thin films in the presence of chemically
      patterned surfaces, where the different contributions to the total free energy,
      the interfacial and bulklike terms, have comparable magnitudes. Here, we report
      on the structures formed by block copolymers films equilibrated between two
      chemically patterned surfaces with orthogonal stripes. Our experiments and
      simulations reveal that the domains are continuous through the film and the
      interface between domains resembles the Scherk's first minimal surface. The
      impact of chemical patterns on block copolymer morphologies and the underlying
      physics gives insight into the nanofabrication of complex nanostructures with
      directed self-assembly using two engineered boundary conditions, as opposed to
      only one.

PMID- 22401085
TI  - Young-type interference for scattering of fast helium atoms from an oxygen
      covered Mo(112) surface.
AB  - In studies on two structures of oxygen adsorbates on Mo(112), we demonstrate the
      potential of fast atom diffraction to derive the surface unit cell size and its
      symmetry. Helium atoms with energies of 1-2 keV are scattered from an adsorbate
      covered Mo(112) surface along low indexed surface directions under grazing angles
      of incidence. From the observed diffraction patterns, the lateral periodicity of
      the surface structures is derived. In addition to the periodic lattice,
      information on the structure within the unit cell can be obtained from double
      slit type of interference.

PMID- 22401086
TI  - Fracture strength of disordered media: universality, interactions, and tail
      asymptotics.
AB  - We study the asymptotic properties of fracture strength distributions of
      disordered elastic media by a combination of renormalization group, extreme value
      theory, and numerical simulation. We investigate the validity of the "weakest
      link hypothesis" in the presence of realistic long-ranged interactions in the
      random fuse model. Numerical simulations indicate that the fracture strength is
      well-described by the Duxbury-Leath-Beale (DLB) distribution which is shown to
      flow asymptotically to the Gumbel distribution. We explore the relation between
      the extreme value distributions and the DLB-type asymptotic distributions and
      show that the universal extreme value forms may not be appropriate to describe
      the nonuniversal low-strength tail.

PMID- 22401087
TI  - Evidence for a phase transition in silicate melt at extreme pressure and
      temperature conditions.
AB  - Laser-driven shock compression experiments reveal the presence of a phase
      transition in MgSiO(3) over the pressure-temperature range 300-400 GPa and 10 000
      16 000 K, with a positive Clapeyron slope and a volume change of ~6.3 (+/-2.0)
      percent. The observations are most readily interpreted as an abrupt liquid-liquid
      transition in a silicate composition representative of terrestrial planetary
      mantles, implying potentially significant consequences for the thermal-chemical
      evolution of extrasolar planetary interiors. In addition, the present results
      extend the Hugoniot equation of state of MgSiO(3) single crystal and glass to 950
      GPa.

PMID- 22401088
TI  - Glass-transition temperature gradient in nanocomposites: evidence from nuclear
      magnetic resonance and differential scanning calorimetry.
AB  - The slowing-down of the dynamics of a polymer chain near a surface has been
      observed for many years now. Here we show that the behavior of model
      nanocomposites can be quantitatively described with a gradient of glass
      transition temperature. We describe with a single parameter-the range of this
      gradient-the temperature and solvent effect on the spin relaxation dynamics.
      Moreover, this parameter allows a quantitative description of the nanocomposite
      calorimetric response from the one of the bulk polymer.

PMID- 22401089
TI  - Isotope fractionation by thermal diffusion in silicate melts.
AB  - Isotopes fractionate in thermal gradients, but there is little quantitative
      understanding of this effect in complex fluids. Here we present results of
      experiments and molecular dynamics simulations on silicate melts. We show that
      isotope fractionation arises from classical mechanical effects, and that a
      scaling relation based on Chapman-Enskog theory predicts the behavior seen in
      complex fluids without arbitrary fitting parameters. The scaling analysis reveals
      that network forming elements (Si and O) fractionate significantly less than
      network modifiers (e.g., Mg, Ca, Fe, Sr, Hf, and U).

PMID- 22401090
TI  - Tuning the growth orientation of epitaxial films by interface chemistry.
AB  - The support of epitaxial films frequently determines their crystallographic
      orientation, which is of crucial importance for their properties. We report a
      novel way to alter the film orientation without changing the substrate. We show
      for the growth of CoO on the Ir(100) surface that, while the oxide grows in (111)
      orientation on the bare substrate, the orientation switches to (100) by
      introducing a single (or a few) monolayer(s) of Co between the oxide and
      substrate. This tunability of the orientation of epitaxial films by the
      appropriate choice of interface chemistry most likely is a general feature.

PMID- 22401091
TI  - Coherent emission from a disordered organic semiconductor induced by strong
      coupling with surface plasmons.
AB  - In this Letter, we show that the strong coupling between a disordered set of
      molecular emitters and surface plasmons leads to the formation of spatially
      coherent hybrid states extended on macroscopic distances. Young-type
      interferometric experiments performed on a system of J-aggregated dyes spread on
      a silver layer evidence the coherent emission from different molecular emitters
      separated by several microns. The coherence is absent in systems in the weak
      coupling regime demonstrating the key role of the hybridization of the molecules
      with the plasmon.

PMID- 22401092
TI  - Metal-to-insulator transition and electron-hole puddle formation in disordered
      graphene nanoribbons.
AB  - The experimentally observed metal-to-insulator transition in hydrogenated
      graphene is numerically confirmed for actual sized graphene samples and realistic
      impurity concentrations. The eigenstates of our tight-binding model with
      substitutional disorder corroborate the formation of electron-hole puddles with
      characteristic length scales comparable to the ones found in experiments. The
      puddles cause charge inhomogeneities and tend to suppress Anderson localization.
      Even though, monitoring the charge carrier quantum dynamics and performing a
      finite-size scaling of the local density of states distribution, we find strong
      evidence for the existence of localized states in graphene nanoribbons with short
      range but also correlated long-range disorder.

PMID- 22401093
TI  - Superconductivity induced by longitudinal ferromagnetic fluctuations in UCoGe.
AB  - From detailed angle-resolved NMR and Meissner measurements on a ferromagnetic
      (FM) superconductor UCoGe (T(Curie)~2.5  K and T(SC)~0.6  K), we show that
      superconductivity in UCoGe is tightly coupled with longitudinal FM spin
      fluctuations along the c axis. We found that magnetic fields along the c axis
      (H?c) strongly suppress the FM fluctuations and that the superconductivity is
      observed in the limited magnetic-field region where the longitudinal FM spin
      fluctuations are active. These results, combined with model calculations,
      strongly suggest that the longitudinal FM spin fluctuations tuned by H?c induce
      the unique spin-triplet superconductivity in UCoGe. This is the first clear
      example that FM fluctuations are intimately related with superconductivity.

PMID- 22401094
TI  - New perspective on formation energies and energy levels of point defects in
      nonmetals.
AB  - We propose a powerful scheme to accurately determine the formation energy and
      thermodynamic charge transition levels of point defects in nonmetals. Previously
      unknown correlations between defect properties and the valence-band width of the
      defect-free host material are identified allowing for a determination of the
      former via an accurate knowledge of the latter. These correlations are identified
      through a series of hybrid density-functional theory computations and an unbiased
      exploration of the parameter space that defines the Hyde-Scuseria-Ernzerhof
      family of hybrid functionals. The applicability of this paradigm is demonstrated
      for point defects in Si, Ge, ZnO, and ZrO2.

PMID- 22401095
TI  - Single-Ion Kondo scaling of the coherent Fermi liquid regime in Ce(1
      x)La(x)Ni2Ge2.
AB  - Thermodynamic and transport properties of the La-diluted Kondo lattice
      CeNi(2)Ge(2) were studied in a wide temperature range. The Ce-rich alloys Ce(1
      x)La(x)Ni(2)Ge(2) were found to exhibit distinct features of the coherent heavy
      Fermi liquid. At intermediate compositions (0.7<=x<=0.9), non-Fermi liquid
      properties have been observed, followed by the local Fermi liquid behavior in the
      dilute limit. The 4f-electron contribution to the specific heat was found to
      follow the predictions of the Kondo-impurity model in both the local as well as
      the coherent regimes, with the characteristic Kondo temperature decreasing
      rapidly from about 30 K for the parent compound CeNi(2)Ge(2) to about 1 K in the
      most dilute samples. The specific heat does not show any evidence for the
      emergence of a new characteristic energy scale related to the formation of the
      coherent Kondo lattice.

PMID- 22401096
TI  - Non-Kondo mechanism for resistivity minimum in spin ice conduction systems.
AB  - We present a mechanism of resistivity minimum in conduction electron systems
      coupled with localized moments, which is distinguished from the Kondo effect.
      Instead of the spin-flip process in the Kondo effect, electrons are elastically
      scattered by local spin correlations which evolve in a particular way under
      geometrical frustration as decreasing temperature. This is demonstrated by the
      cellular dynamical mean-field theory for a spin-ice-type Kondo lattice model on a
      pyrochlore lattice. Peculiar temperature dependences of the resistivity, specific
      heat, and magnetic susceptibility in the non-Kondo mechanism are compared with
      the experimental data in metallic Ir pyrochlore oxides.

PMID- 22401097
TI  - Superconducting pairs with extreme uniaxial anisotropy in URu2Si2.
AB  - We report magnetic field orientation-dependent measurements of the
      superconducting upper critical field in high quality single crystals of
      URu(2)Si(2) and find the effective g factor estimated from the Pauli limit to
      agree remarkably well with that found in quantum oscillation experiments, both
      quantitatively and in the extreme anisotropy (~10(3)) of the spin susceptibility.
      Rather than a strictly itinerant or purely local f-electron picture being
      applicable, the latter suggests the quasiparticles subject to pairing in
      URu(2)Si(2) to be "composite heavy fermions" formed from bound states between
      conduction electrons and local moments with a protected Ising behavior. Non
      Kramers doublet local magnetic degrees of freedom suggested by the extreme
      anisotropy favor a local pairing mechanism.

PMID- 22401098
TI  - Electric field confinement effect on charge transport in organic field-effect
      transistors.
AB  - While it is known that the charge-carrier mobility in organic semiconductors is
      only weakly dependent on the electric field at low fields, the experimental
      mobility in organic field-effect transistors using silylethynyl-substituted
      pentacene is found to be surprisingly field dependent at low source-drain fields.
      Corroborated by scanning Kelvin probe measurements, we explain this observation
      by the severe difference between local conductivities within grains and at grain
      boundaries. Redistribution of accumulated charges creates very strong local
      lateral fields in the latter regions. We further confirm this picture by
      verifying that the charge mobility in channels having no grain boundaries, made
      from the same organic semiconductor, is not significantly field dependent. We
      show that our model allows us to quantitatively model the source-drain field
      dependence of the mobility in polycrystalline organic transistors.

PMID- 22401099
TI  - Ground state of the parallel double quantum dot system.
AB  - We resolve the controversy regarding the ground state of the parallel double
      quantum dot system near half filling. The numerical renormalization group
      predicts an underscreened Kondo state with residual spin-1/2 magnetic moment, ln2
      residual impurity entropy, and unitary conductance, while the Bethe ansatz
      solution predicts a fully screened impurity, regular Fermi-liquid ground state,
      and zero conductance. We calculate the impurity entropy of the system as a
      function of the temperature using the hybridization-expansion continuous-time
      quantum Monte Carlo technique, which is a numerically exact stochastic method,
      and find excellent agreement with the numerical renormalization group results. We
      show that the origin of the unconventional behavior in this model is the odd
      symmetry "dark state" on the dots.

PMID- 22401100
TI  - Bethe ansatz approach to the Kondo effect within density-functional theory.
AB  - Transport through an Anderson junction (two macroscopic electrodes coupled to an
      Anderson impurity) is dominated by a Kondo peak in the spectral function at zero
      temperature. We show that the single-particle Kohn-Sham potential of density
      functional theory reproduces the linear transport, despite the lack of a Kondo
      peak in its spectral function. Using Bethe ansatz techniques, we calculate this
      potential for all coupling strengths, including the crossover from mean-field
      behavior to charge quantization caused by the derivative discontinuity. A simple
      and accurate interpolation formula is also given.

PMID- 22401101
TI  - Non-Abelian braiding of lattice bosons.
AB  - We report on a numerical experiment in which we use time-dependent potentials to
      braid non-Abelian quasiparticles. We consider lattice bosons in a uniform
      magnetic field within the fractional quantum Hall regime, where nu, the ratio of
      particles to flux quanta, is near 1/2, 1, or 3/2. We introduce time-dependent
      potentials which move quasiparticle excitations around one another, explicitly
      simulating a braiding operation which could implement part of a gate in a quantum
      computation. We find that different braids do not commute for nu near 1 and 3/2,
      with Berry matrices, respectively, consistent with Ising and Fibonacci anyons.
      Near nu=1/2, the braids commute.

PMID- 22401102
TI  - Realizing the multiparticle Hanbury Brown-Twiss interferometer using nitrogen
      vacancy centers in diamond crystals.
AB  - We demonstrate that the multiparticle Hanbury Brown-Twiss interferometer can be
      realized in a network of nitrogen-vacancy centers: for an N-particle system, the
      interference effect is manifested only in the Nth-order intensity correlation
      function. The interference effect can be enhanced through a postselection process
      in which the multipartite Greenberger-Horne-Zeilinger entanglement is generated
      and tested with Svetlichny inequality.

PMID- 22401103
TI  - Ir(111) surface state with giant Rashba splitting persists under graphene in air.
AB  - We reveal a giant Rashba effect (alpha(R)~1.3  eV A) on a surface state of
      Ir(111) by angle-resolved photoemission and by density functional theory. It is
      demonstrated that the existence of the surface state, its spin polarization, and
      the size of its Rashba-type spin-orbit splitting remain unaffected when Ir is
      covered with graphene. The graphene protection is, in turn, sufficient for the
      spin-split surface state to survive in ambient atmosphere. We discuss this result
      along with indications for a topological protection of the surface state.

PMID- 22401104
TI  - Hall viscosity and electromagnetic response.
AB  - We show that, for Galilean invariant quantum Hall states, the Hall viscosity
      appears in the electromagnetic response at finite wave numbers q. In particular,
      the leading q dependence of the Hall conductivity at small q receives a
      contribution from the Hall viscosity. The coefficient of the q(2) term in the
      Hall conductivity is universal in the limit of strong magnetic field.

PMID- 22401105
TI  - Hierarchical nature of the quantum Hall effects.
AB  - I demonstrate that the wave function for a nu=n+nu[over ~] quantum Hall state
      with Landau levels 0,1,...,n-1 filled and a filling fraction nu[over ~] quantum
      Hall state with 0<nu[over ~]<=1 in the nth Landau level can be obtained
      hierarchically from the nu=n state by introducing quasielectrons which are then
      projected into the (conjugate of the) nu[over ~] state. In particular, the
      nu[over ~]=1 case produces the filled Landau level wave functions hierarchically,
      thus establishing the hierarchical nature of the integer quantum Hall states. It
      follows that the composite fermion description of fractional quantum Hall states
      fits within the hierarchy theory of the fractional quantum Hall effect. I also
      demonstrate this directly by generating the composite fermion ground-state wave
      functions via application of the hierarchy construction to fractional quantum
      Hall states, starting from the nu=1/m Laughlin states.

PMID- 22401106
TI  - Large conductance modulation of gold thin films by huge charge injection via
      electrochemical gating.
AB  - By using an electrochemical gating technique with a new combination of polymer
      and electrolyte, we were able to inject surface charge densities n(2D) as high as
      3.5*10(15)  e/cm(2) in gold films and to observe large relative variations in the
      film resistance, DeltaR/R', up to 10% at low temperature. DeltaR/R' is a linear
      function of n(2D)-as expected within a free-electron model-if the film is thick
      enough (>=25  nm); otherwise, a tendency to saturation due to size effects is
      observed. The application of this technique to 2D materials might allow extending
      the field-effect experiments to a range of charge doping where large conductance
      modulations and, in some cases, even the occurrence of superconductivity are
      expected.

PMID- 22401107
TI  - Spin-polarized Dirac-cone-like surface state with d character at W(110).
AB  - The surface of W(110) exhibits a Dirac-cone-like state with d character within a
      spin-orbit-induced symmetry gap. As a function of the wave vector parallel to the
      surface, it shows a nearly massless energy dispersion and a pronounced spin
      polarization, which is antisymmetric with respect to the Brillouin zone center.
      In addition, the observed constant energy contours are strongly anisotropic for
      all energies. This discovery opens new pathways to the study of surface spin
      density waves arising from a strong Fermi surface nesting as well as d-electron
      based topological properties.

PMID- 22401108
TI  - Fermi-level tuning of epitaxial Sb2Te3 thin films on graphene by regulating
      intrinsic defects and substrate transfer doping.
AB  - High-quality Sb2Te3 films are obtained by molecular beam epitaxy on a graphene
      substrate and investigated by in situ scanning tunneling microscopy and
      spectroscopy. Intrinsic defects responsible for the natural p-type conductivity
      of Sb2Te3 are identified to be the Sb vacancies and Sb(Te) antisites in agreement
      with first-principles calculations. By minimizing defect densities, coupled with
      a transfer doping by the graphene substrate, the Fermi level of Sb2Te3 thin films
      can be tuned over the entire range of the bulk band gap. This establishes the
      necessary condition to explore topological insulator behaviors near the Dirac
      point.

PMID- 22401109
TI  - NMR probing of the spin polarization of the nu=5/2 quantum Hall state.
AB  - Resistively detected nuclear magnetic resonance is used to measure the Knight
      shift of the 75As nuclei and determine the electron spin polarization of the
      fractional quantum Hall states of the second Landau level. We show that the 5/2
      state is fully polarized within experimental error, thus confirming a fundamental
      assumption of the Moore-Read theory. We measure the electron heating under radio
      frequency excitation and show that we are able to detect NMR at electron
      temperatures down to 30 mK.

PMID- 22401110
TI  - Avoidance of Majorana resonances in periodic topological superconductor-nanowire
      structures.
AB  - Semiconducting nanowires in proximity to superconductors are promising
      experimental systems for Majorana fermions which may ultimately be used as
      building blocks for topological quantum computers. A serious challenge in the
      experimental realization of the Majorana fermion in these semiconductor
      superconductor-nanowire structures is tuning the semiconductor chemical potential
      in close proximity to the metallic superconductor. We show that presently
      realizable structures in experiments with tunable chemical potential lead to
      Majorana resonances, which are interesting in their own right, but do not
      manifest non-Abelian statistics. To resolve this crucial barrier to the solid
      state realization of Majorana fermions, we propose a new topological
      superconducting array structure where introducing the superconducting proximity
      effect from adjacent nanowires generates Majorana fermions with non-Abelian
      statistics.

PMID- 22401111
TI  - Manifestly non-Gaussian fluctuations in superconductor-normal metal tunnel
      nanostructures.
AB  - We propose a mesoscopic setup which exhibits strong and manifestly non-Gaussian
      fluctuations of energy and temperature when suitably driven out of equilibrium.
      The setup consists of a normal metal island (N) coupled by tunnel junctions (I)
      to two superconducting leads (S), forming a SINIS structure, and is biased near
      the threshold voltage for quasiparticle tunneling, eV~2Delta. The fluctuations
      can be measured by monitoring the time-dependent electric current through the
      system. This makes the setup suitable for the realization of feedback schemes
      which can be used to stabilize the temperature to the desired value.

PMID- 22401112
TI  - Quantum order-by-disorder near criticality and the secret of partial order in
      MnSi.
AB  - The vicinity of quantum phase transitions has proven fertile ground in the search
      for new quantum phases. We propose a physically motivated and unifying
      description of phase reconstruction near metallic quantum-critical points using
      the idea of quantum order by disorder. Certain deformations of the Fermi surface
      associated with the onset of competing order enhance the phase space available
      for low-energy, particle-hole fluctuations and self-consistently lower the free
      energy. Applying the notion of quantum order by disorder to the itinerant
      helimagnet MnSi, we show that, near the quantum critical point, fluctuations lead
      to an increase of the spiral ordering wave vector and a reorientation away from
      the lattice-favored directions. The magnetic ordering pattern in this fluctuation
      driven phase is found to be in excellent agreement with the neutron-scattering
      data in the partially ordered phase of MnSi.

PMID- 22401113
TI  - Indications of an electronic phase transition in two-dimensional superconducting
      YBa2Cu3O(7-x) thin films induced by electrostatic doping.
AB  - We successfully tuned an underdoped ultrathin YBa2Cu3O(7-x) film into the
      overdoped regime by means of electrostatic doping using an ionic liquid as a
      dielectric material. This process proved to be reversible. Transport measurements
      showed a series of anomalous features compared to chemically doped bulk samples
      and a different two-step doping mechanism for electrostatic doping was revealed.
      The normal resistance increased with carrier concentration on the overdoped side
      and the high temperature (180 K) Hall number peaked at a doping level of p~0.15.
      These anomalous behaviors suggest that there is an electronic phase transition in
      the Fermi surface around the optimal doping level.

PMID- 22401114
TI  - Giant improper ferroelectricity in the ferroaxial magnet CaMn7O12.
AB  - In rhombohedral CaMn7O12, an improper ferroelectric polarization of magnitude
      2870  MUC  m(-2) is induced by an incommensurate helical magnetic structure that
      evolves below T(N1)=90 K. The electric polarization was found to be constrained
      to the high symmetry threefold rotation axis of the crystal structure,
      perpendicular to the in-plane rotation of the magnetic moments. The
      multiferroicity is explained by the ferroaxial coupling mechanism, which in
      CaMn7O12 gives rise to the largest magnetically induced, electric polarization
      measured to date.

PMID- 22401115
TI  - Variational numerical renormalization group: bridging the gap between NRG and
      density matrix renormalization group.
AB  - The numerical renormalization group (NRG) is rephrased as a variational method
      with the cost function given by the sum of all the energies of the effective low
      energy Hamiltonian. This allows us to systematically improve the spectrum
      obtained by NRG through sweeping. The ensuing algorithm has a lot of similarities
      to the density matrix renormalization group (DMRG) when targeting many states,
      and this synergy of NRG and DMRG combines the best of both worlds and extends
      their applicability. We illustrate this approach with simulations of a quantum
      spin chain and a single impurity Anderson model where the accuracy of the
      effective eigenstates is greatly enhanced as compared to the NRG, especially in
      the transition to the continuum limit.

PMID- 22401116
TI  - Magnetotransport at domain walls in BiFeO3.
AB  - Domain walls in multiferroics can exhibit intriguing behaviors that are
      significantly different from the bulk of the material. We investigate strong
      magnetoresistance in domain walls of the model multiferroic BiFeO3 by probing
      ordered arrays of 109 degrees  domain walls with temperature- and magnetic-field
      dependent transport. We observe temperature-dependent variations in the transport
      mechanism and magnetoresistances as large as 60%. These results suggest that by
      locally breaking the symmetry of a material, such as at domain walls and
      structural interfaces, one can induce emergent behavior with properties that
      deviate significantly from the bulk.

PMID- 22401117
TI  - Quantum ice: a quantum Monte Carlo study.
AB  - Ice states, in which frustrated interactions lead to a macroscopic ground-state
      degeneracy, occur in water ice, in problems of frustrated charge order on the
      pyrochlore lattice, and in the family of rare-earth magnets collectively known as
      spin ice. Of particular interest at the moment are "quantum spin-ice" materials,
      where large quantum fluctuations may permit tunnelling between a macroscopic
      number of different classical ground states. Here we use zero-temperature quantum
      Monte Carlo simulations to show how such tunnelling can lift the degeneracy of a
      spin or charge ice, stabilizing a unique "quantum-ice" ground state-a quantum
      liquid with excitations described by the Maxwell action of (3+1)-dimensional
      quantum electrodynamics. We further identify a competing ordered squiggle state,
      and show how both squiggle and quantum-ice states might be distinguished in
      neutron scattering experiments on a spin-ice material.

PMID- 22401118
TI  - Direct observation of unconventional topological spin structure in coupled
      magnetic discs.
AB  - Confined magnetic thin films are known to exhibit a variety of fascinating
      topological spin states such as Skyrmions, vortices, and antivortices. Such
      topological excitations are fundamentally important to our understanding of
      quantum critical phenomenon and related phase transitions. Here we report on the
      direct observation of an unconventional topological spin state and its behavior
      in antiferromagnetically coupled NiFe discs at room temperature. The observed
      spin structure is similar to the theoretically predicted merons which have not
      yet been observed directly. We have used in situ Lorentz microscopy magnetizing
      experiments combined with micromagnetic simulations to follow the stability and
      the behavior of the meron state. The work presented in this paper will open new
      opportunities for direct experimental investigation of various topological states
      that can provide insights into the fundamental physics of their interactions.

PMID- 22401119
TI  - Coherent manipulation of electron spins in the {Cu3} spin triangle complex
      impregnated in nanoporous silicon.
AB  - We report on coherent manipulation of electron spins in an antiferromagnetically
      coupled spin triangle {Cu3-X} (X=As, Sb) impregnated in freestanding nanoporous
      silicon (NS) by using 240 GHz microwave pulses. Rabi oscillations are observed
      and the spin coherence time is found to be T(2)=1066 ns at 1.5 K. This
      demonstrates that the {Cu3-X}:NS hybrid material provides a promising scheme for
      implementing spin-based quantum gates. By measuring the spin relaxation times of
      samples with different symmetries and environments we give evidence that a spin
      chirality is the main decoherence source of spin triangle molecules.

PMID- 22401121
TI  - Persistence of covalent bonding in liquid silicon probed by inelastic x-ray
      scattering.
AB  - Metallic liquid silicon at 1787 K is investigated using x-ray Compton scattering.
      An excellent agreement is found between the measurements and the corresponding
      Car-Parrinello molecular dynamics simulations. Our results show persistence of
      covalent bonding in liquid silicon and provide support for the occurrence of
      theoretically predicted liquid-liquid phase transition in supercooled liquid
      states. The population of covalent bond pairs in liquid silicon is estimated to
      be 17% via a maximally localized Wannier function analysis. Compton scattering is
      shown to be a sensitive probe of bonding effects in the liquid state.

PMID- 22401120
TI  - Weak exciton scattering in molecular nanotubes revealed by double-quantum two
      dimensional electronic spectroscopy.
AB  - The two-exciton manifold of a double-wall cylindrical molecular aggregate is
      studied using a coherent third order optical technique. Experiments reveal the
      anharmonic character of the exciton bands. Atomistic simulations of the exciton
      exciton scattering show that the excitons can be treated as weakly coupled hard
      core bosons. The weak coupling stems from the extended exciton delocalization
      made possible by the nanotube geometry.

PMID- 22401122
TI  - Absence of ferroelectric critical size in ultrathin PbTiO3 nanotubes: a density
      functional theory study.
AB  - We simulate from first principles the energetic, structural, and electronic
      properties of ferroelectric (FE) ultrathin PbTiO3 nanotubes. The nanotube
      possesses spontaneous polarization despite their sidewalls being thinner than the
      critical thickness at which the thin films lose ferroelectricity; this indicates
      the absence of an intrinsic critical size for ferroelectricity. The ground state
      of the nanotube is not purely FE since it primarily involves antiferrodistortive
      (AFD) rotations of oxygen atoms due to compression in the inner tube wall. The
      emergence of the AFD displacement plays a central role in stabilizing both the
      nanotubular structure and FE distortions due to direct AFD-FE coupling. Moreover,
      we predict intriguing rich phase transitions due to axial strains including
      polarization vortices as an important class of nanoscale FE ordering.

PMID- 22401123
TI  - Dynamic structure factor of vibrating fractals.
AB  - Motivated by novel experimental work and the lack of an adequate theory, we study
      the dynamic structure factor S(k,t) of large vibrating fractal networks at large
      wave numbers k. We show that the decay of S(k,t) is dominated by the spatially
      averaged mean square displacement of a network node, which evolves subdiffusively
      in time, ((u[over ->](i)(t)-u[over ->](i)(0))(2))~t(nu), where nu depends on the
      spectral dimension d(s) and fractal dimension d(f). As a result, S(k,t) decays as
      a stretched exponential S(k,t)~S(k)e(-(Gamma(k)t)(nu)) with Gamma(k)~k(2/nu).
      Applications to a variety of fractal-like systems are elucidated.

PMID- 22401124
TI  - Self-organized transition to coherent activity in disordered media.
AB  - Synchronized oscillations are of critical functional importance in many
      biological systems. We show that such oscillations can arise without centralized
      coordination in a disordered system of electrically coupled excitable and passive
      cells. Increasing the coupling strength results in waves that lead to coherent
      periodic activity, exhibiting cluster, local and global synchronization under
      different conditions. Our results may explain the self-organized transition in a
      pregnant uterus from transient, localized activity initially to system-wide
      coherent excitations just before delivery.

PMID- 22401125
TI  - Intrinsic stability of a body hovering in an oscillating airflow.
AB  - We explore the stability of flapping flight in a model system that consists of a
      pyramid-shaped object hovering in a vertically oscillating airflow. Such a flyer
      not only generates sufficient aerodynamic force to keep aloft but also robustly
      maintains balance during free flight. Flow visualization reveals that both weight
      support and orientational stability result from the periodic shedding of
      vortices. We explain these findings with a model of the flight dynamics, predict
      increasing stability for higher center of mass, and verify this counterintuitive
      fact by comparing top- and bottom-heavy flyers.

PMID- 22401126
TI  - Layering instability in a confined suspension flow.
AB  - We show [J. Fluid Mech. 592, 447 (2007)] that swapping (reversing) trajectories
      in confined suspension flows prevent collisions between particles approaching
      each other in adjacent streamlines. Here we demonstrate that by inducing layering
      this hydrodynamic mechanism changes the microstructure of suspensions in a
      confined Couette flow. Layers occur either in the near-wall regions or span the
      whole channel width, depending on the strength of the swapping-trajectory effect.
      While our theory focuses on dilute suspensions, we postulate that this new
      hydrodynamic mechanism controls the formation of a layered microstructure in a
      wide range of densities.

PMID- 22401127
TI  - Identification of potential photovoltaic absorbers based on first-principles
      spectroscopic screening of materials.
AB  - There are numerous inorganic materials that may qualify as good photovoltaic (PV)
      absorbers, except that the currently available selection principle-focusing on
      materials with a direct band gap of ~1.3 eV (the Shockley-Queisser criteria)-does
      not provide compelling design principles even for the initial material screening.
      Here we offer a calculable selection metric of "spectroscopic limited maximum
      efficiency (SLME)" that can be used for initial screening based on intrinsic
      properties alone. It takes into account the band gap, the shape of absorption
      spectra, and the material-dependent nonradiative recombination losses. This is
      illustrated here via high-throughput first-principles quasiparticle calculations
      of SLME for ~260 generalized I(p)III(q)VI(r) chalcopyrite materials. It
      identifies over 20 high-SLME materials, including the best known as well as
      previously unrecognized PV absorbers.

PMID- 22401128
TI  - Comparative evaluation of the effects of different photoablative laser
      irradiation protocols on the gingiva of periodontopathic patients.
AB  - OBJECTIVE: We aimed at quantifying the presence of periodontopathogens in
      gingival biopsies from periodontitis patients treated with different
      photoablative lasers (diode GaAs, Er:YAG, Nd:YAG, and CO(2) lasers) and
      histologically analyzing their effects on the gingiva. BACKGROUND DATA:
      Substantial evidence indicates that intracellular location of periodontal
      bacteria in the gingival epithelium may contribute to chronic periodontitis.
      METHODS: Sixteen adult subjects with chronic periodontitis were subjected to
      conventional scaling/root planing and topical chlorhexidine, and immediately
      laser-irradiated on the inner and outer free gingiva. Small gingival biopsies
      were subjected to real-time polymerase chain reaction and cytofluorescence to
      identify periodontopathogens; tissue damage and endothelial ICAM-1 expression
      were assessed by histological and immunofluorescence analyses. RESULTS: High DNA
      levels of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans,
      Fusobacterium nucleatum, Treponema denticola, Prevotella intermedia, and Ekenella
      corrodens, were detected in all samples. Nd:YAG and diode lasers were capable of
      eradicating periodontopathogenic bacteria endowed within gingival epithelial
      cells outside periodontal pockets, without causing connective tissue damage and
      microvessel rupture. They also reduced ICAM-1 immunolabelling by the vascular
      endothelium. Conversely, Er:YAG lasers induced marked microvessel rupture and
      bleeding and failed to completely and selectively ablate the infected gingival
      epithelium, whereas CO(2) laser caused heat-induced coagulation of the lamina
      propria. CONCLUSIONS: This study indicates that periodontopathogens can persist
      within cells outside the pocket epithelium, despite conventional periodontal
      treatment. Nd:YAG and diode lasers are able to eradicate intra- and extracellular
      bacteria from these sites, suggesting that they can be considered suitable
      devices to improve the clinical outcome of periodontal disease.

PMID- 22401129
TI  - Minding the mind in photobiomodulation: it matters!

PMID- 22401130
TI  - The use and interpretation of serum retinol distributions in evaluating the
      public health impact of vitamin A programmes.
AB  - OBJECTIVE: Developing countries have adopted universal, high-potency vitamin A
      (VA) supplementation and food fortification as major strategies to control
      deficiency, prevent nutritional blindness and reduce child mortality. Yet
      questions persist regarding how best to measure impact and when to phase out
      supplementation. The present paper provides guidance on the use and
      interpretation of serum retinol (SROL) distributions as indicators of both
      programme impact and adequate VA intake in a population. DESIGN: We reviewed
      extant data on SROL's response to high-potency VA supplementation and VA
      fortified foods in children. RESULTS: Supplementation virtually eliminates
      xerophthalmia and reduces child mortality; however, it shifts the SROL
      distribution only transiently (<2 months). Regular consumption of VA-fortified
      foods prevents xerophthalmia, lowers mortality and sustainably improves SROL
      distributions, from which both compliance and public health impact can be
      inferred. CONCLUSIONS: Given SROL's limited responsiveness to high-potency VA
      supplementation, target population coverage remains the preferred performance
      indicator. However, periodic SROL surveys do reflect underlying dietary risk and
      can guide programming: low or marginal SROL distributions in areas with high
      supplementation coverage do not signify programme failure, but rather suggest the
      need to continue supplementation while working to effectively raise dietary VA
      intakes. We propose that a sustained rise in the SROL distribution, defined as
      <=5 % prevalence of SROL < 0.70 MUmol/l among vulnerable population groups in at
      least two consecutive surveys (>=1 year apart), be used as an indicator of stable
      and adequate dietary VA intake and status in a population, at which point
      programmes may re-evaluate the need for continued universal supplementation.

PMID- 22401131
TI  - Tracor, inc.

PMID- 22401132
TI  - Sequence, structure, and function of peptide self-assembled monolayers.
AB  - Cysteine is commonly used to attach peptides onto gold surfaces. Here we show
      that the inclusion of an additional linker with a length of four residues (
      PPPPC) and a rigid, hydrophobic nature is a better choice for forming peptide
      self-assembled monolayers (SAMs) with a well-ordered structure and high surface
      density. We compared the structure and function of the nonfouling peptide EKEKEKE
      PPPPC-Am with EKEKEKE-C-Am. Circular dichroism, attenuated total internal
      reflection Fourier transform IR spectroscopy, and molecular dynamics results
      showed that EKEKEKE-PPPPC-Am forms a secondary structure while EKEKEKE-C-Am has a
      random structure. Surface plasmon resonance sensor results showed that protein
      adsorption on EKEKEKE-PPPPC-Am/gold is very low with small variation while
      protein adsorption on EKEKEKE-C-Am/gold is high with large variation. X-ray
      photoelectron spectroscopy results showed that both peptides have strong gold
      thiol binding with the gold surface, indicating that their difference in protein
      adsorption is due to their assembled structures. Further experimental and
      simulation studies were performed to show that -PPPPC is a better linker than 
      PC, -PPC, and -PPPC. Finally, we extended EKEKEKE-PPPPC-Am with the cell-binding
      sequence RGD and demonstrated control over specific versus nonspecific cell
      adhesion without using poly(ethylene glycol). Adding a functional peptide to the
      nonfouling EK sequence avoids complex chemistries that are used for its
      connection to synthetic materials.

PMID- 22401133
TI  - Outcomes after anti-rheumatic drug use before and during pregnancy: a cohort
      study among 150,000 pregnant women and expectant fathers.
AB  - OBJECTIVES: To study (i) the drug utilization pattern of anti-rheumatic drugs in
      pregnant women and expectant fathers and (ii) the association between the use of
      anti-rheumatic drugs during pregnancy and the risk of congenital malformations.
      METHOD: Pregnancies registered in the Medical Birth Registry of Norway (MBRN)
      were linked to the Norwegian Prescription Database (NorPD) in the period 2004
      2007. Prescriptions for anti-rheumatic drugs issued to women 3 months prior to
      and during pregnancy and to men 3 months prior to conception were identified.
      Congenital malformations were recorded according to the European Surveillance of
      Congenital Anomalies (EUROCAT) guidelines. RESULTS: In 154,976 singleton
      pregnancies, 1461 of the women (0.9%) and 1198 (0.8%) of the known fathers
      (150,530) were dispensed anti-rheumatic drugs at least once during the study
      period: 723 had non-steroidal anti-inflammatory drugs (NSAIDs), 633 prednisolone
      (CS), 119 sulfasalazine (SASP), 101 azathioprine (AZA), 58 hydroxychloroquine
      (HQC), 37 etanercept (ETAN), eight methotrexate (MTX), two leflunomide (LEF), and
      three adalumimab (ADA). Odds ratios (ORs) for malformations in children born of
      women (w) or men (m) who had received the drugs were OR(w) = 1.06 [95% confidence
      interval (CI) 0.85-1.32] and OR(m) = 1.19 (95% CI 0.93-1.51), respectively, and
      for major malformation OR(w) = 1.05 (95% CI 0.79-1.40) and OR(m) = 1.26 (95% CI
      0.93-1.71), respectively. None of the children whose mother had received MTX,
      LEF, ETAN, or ADA were reported to be born with major malformations. CONCLUSIONS:
      This study revealed no major malformations of the alert drugs MTX, LEF, ETAN, or
      ADA. Although the numbers are limited, this provides important population-based
      information to both expectant parents and prescribers.

PMID- 22401134
TI  - Mechanism of binding of NO to soluble guanylyl cyclase: implication for the
      second NO binding to the heme proximal site.
AB  - Soluble guanylyl cyclase (sGC), the key enzyme for the formation of second
      messenger cyclic GMP, is an authentic sensor for nitric oxide (NO). Binding of NO
      to sGC leads to strong activation of the enzyme activity. Multiple molecules and
      steps of binding of NO to sGC have been implicated, but the target of the second
      NO and the detailed binding mechanism remain controversial. In this study, we
      used (15)NO and (14)NO and anaerobic sequential mixing-freeze-quench electron
      paramagnetic resonance to unambiguously confirm that the heme Fe is the target of
      the second NO. The linear dependence on NO concentration up to 600 s(-1) for the
      observed rate of the second step of NO binding not only indicates that the
      binding site of the second NO is different from that in the first step, i.e., the
      proximal site of the heme, but also supports a concerted mechanism in which the
      dissociation of the His105 proximal ligand occurs simultaneously with the binding
      of the second NO molecule. Computer modeling successfully predicts the kinetics
      of formation of a set of five-coordinate NO complexes with the ligand on either
      the distal or proximal site and supports the selective release of NO from the
      distal side of the transient bis-NO-sGC complex. Thus, as has been demonstrated
      with cytochrome c', a five-coordinate NO-sGC complex containing a proximal NO is
      formed after the binding of the second NO.

PMID- 22401135
TI  - Regression dilution bias: tools for correction methods and sample size
      calculation.
AB  - BACKGROUND: Random errors in measurement of a risk factor will introduce downward
      bias of an estimated association to a disease or a disease marker. This
      phenomenon is called regression dilution bias. A bias correction may be made with
      data from a validity study or a reliability study. AIMS AND METHODS: In this
      article we give a non-technical description of designs of reliability studies
      with emphasis on selection of individuals for a repeated measurement, assumptions
      of measurement error models, and correction methods for the slope in a simple
      linear regression model where the dependent variable is a continuous variable.
      Also, we describe situations where correction for regression dilution bias is not
      appropriate. RESULTS: The methods are illustrated with the association between
      insulin sensitivity measured with the euglycaemic insulin clamp technique and
      fasting insulin, where measurement of the latter variable carries noticeable
      random error. We provide software tools for estimation of a corrected slope in a
      simple linear regression model assuming data for a continuous dependent variable
      and a continuous risk factor from a main study and an additional measurement of
      the risk factor in a reliability study. Also, we supply programs for estimation
      of the number of individuals needed in the reliability study and for choice of
      its design. CONCLUSIONS: Our conclusion is that correction for regression
      dilution bias is seldom applied in epidemiological studies. This may cause
      important effects of risk factors with large measurement errors to be neglected.

PMID- 22401136
TI  - Regional variation in use of exogenous and endogenous glomerular filtration rate
      (GFR) markers in Sweden.
AB  - BACKGROUND: Markers of renal function (glomerular filtration rate (GFR)) are
      frequently used in the Swedish health care. GFR is usually estimated based on
      plasma creatinine concentration, but plasma cystatin C concentration, creatinine
      clearance, iohexol clearance, and (51)Cr-EDTA clearance are also used. These
      markers are all part of the daily patient care, but there is little specific
      information on the clinical use of these markers. The aim of this study was to
      compare the use of these various GFR markers in different parts of Sweden and
      potential changes over time. METHODS: Retrospective study using questionnaires to
      collect information for the years 2006-2009 divided per county on the specific
      use of GFR markers with type of test reports. RESULTS: Plasma/serum creatinine
      concentration (96%) is by far the dominating GFR marker in Sweden, while cystatin
      C concentration (3.5%), creatinine clearance (0.1%), iohexol clearance (0.1%),
      and 51Cr-EDTA clearance (0.1%) are less frequently used. The use of GFR markers,
      including creatinine, continues to increase on a national level with the
      exception of creatinine clearance and 51Cr-EDTA clearance. There were
      considerable variations between different counties in the use of GFR markers and
      the type of test reports that the laboratories provided. CONCLUSIONS: The inter
      county variations of GFR markers used in Sweden are large and indicate that
      savings associated with optimized test utilization in this regard could be
      substantial. Regional habits and traditions are likely to influence the
      variations in GFR marker use.

PMID- 22401137
TI  - Analysis of SLX4/FANCP in non-BRCA1/2-mutated breast cancer families.
AB  - BACKGROUND: Genes that, when mutated, cause Fanconi anemia or greatly increase
      breast cancer risk encode for proteins that converge on a homology-directed DNA
      damage repair process. Mutations in the SLX4 gene, which encodes for a scaffold
      protein involved in the repair of interstrand cross-links, have recently been
      identified in unclassified Fanconi anemia patients. A mutation analysis of SLX4
      in German or Byelorussian familial cases of breast cancer without detected
      mutations in BRCA1 or BRCA2 has been completed, with globally negative results.
      METHODS: The genomic region of SLX4, comprising all exons and exon-intron
      boundaries, was sequenced in 94 Spanish familial breast cancer cases that match a
      criterion indicating the potential presence of a highly-penetrant germline
      mutation, following exclusion of BRCA1 or BRCA2 mutations. RESULTS: This
      mutational analysis revealed extensive genetic variation of SLX4, with 21 novel
      single nucleotide variants; however, none could be linked to a clear alteration
      of the protein function. Nonetheless, genotyping 10 variants (nine novel, all
      missense amino acid changes) in a set of controls (138 women and 146 men) did not
      detect seven of them. CONCLUSIONS: Overall, while the results of this study do
      not identify clearly pathogenic mutations of SLX4 contributing to breast cancer
      risk, further genetic analysis, combined with functional assays of the identified
      rare variants, may be warranted to conclusively assess the potential link with
      the disease.

PMID- 22401138
TI  - Preparation and characterization of ZnO microcantilever for nanoactuation.
AB  - Zinc oxide [ZnO] thin films are deposited using a radiofrequency magnetron
      sputtering method under room temperature. Its crystalline quality, surface
      morphology, and composition purity are characterized by X-ray diffraction [XRD],
      atomic force microscopy [AFM], field-emission scanning electron microscopy [FE
      SEM], and energy-dispersive X-ray spectroscopy [EDS]. XRD pattern of the ZnO thin
      film shows that it has a high c-axis-preferring orientation, which is confirmed
      by a FE-SEM cross-sectional image of the film. The EDS analysis indicates that
      only Zn and O elements are contained in the ZnO film. The AFM image shows that
      the film's surface is very smooth and dense, and the surface roughness is 5.899
      nm. The microcantilever (Au/Ti/ZnO/Au/Ti/SiO2/Si) based on the ZnO thin film is
      fabricated by micromachining techniques. The dynamic characterizations of the
      cantilever using a laser Doppler vibrometer show that the amplitude of the
      cantilever tip is linear with the driving voltage, and the amplitude of this
      microcantilever's tip increased from 2.1 to 13.6 nm when the driving voltage
      increased from 0.05 to 0.3 Vrms. The calculated transverse piezoelectric constant
      d31 of the ZnO thin film is -3.27 pC/N. This d31 is high compared with other
      published results. This ZnO thin film will be used in smart slider in hard disk
      drives to do nanoactuation in the future.

PMID- 22401140
TI  - Synergistic effects in La/N codoped TiO2 anatase (101) surface correlated with
      enhanced visible-light photocatalytic activity.
AB  - The interaction between implanted La, substitutional N, and an oxygen vacancy at
      TiO(2) anatase (101) surface has been investigated by means of first-principles
      density function theory calculations to investigate the origin of enhanced
      visible-light photocatalytic activity of La/N-codoped anatase observed in
      experiments. Our calculations suggest that both the adsorptive and substitutional
      La-doped TiO(2) anatase (101) surfaces are probably defective configurations in
      experiments. The h-Cave-adsorbed La doping decreases the formation energy for the
      substitutional N implantation and vice versa, while the charge compensation
      effects do not take effect between the adsorptive La and substitutional N
      dopants, resulting in some partially occupied states in the band gap acting as
      traps of the photoexcited electrons. The Ti(5c)-substituted La doping decreases
      the energy required for the substitutional N implantation, and the substitutional
      La and N codoping promotes the formation of an oxygen vacancy, which migrates
      from the O(sb-3c) site at the inner layer toward the surface O(b) site. For the
      substitutional La/N-codoped (Ti(5c)_O(3c-down)) surface, the charge compensation
      between the substitutional La and substitutional N leads to the formation of two
      isolated occupied N(s)-O pi* impurity levels in the gap, while the excitation
      energy from the higher impurity level to the CBM decreases by about 0.89 eV.
      After further considering an oxygen vacancy on the Ti(5c)_O(3c-down) surface, the
      two electrons on the double donor levels (O(b) vacancy) passivate the same amount
      of holes on the acceptor levels (substitutional La and N), forming the acceptor
      donor-acceptor compensation pair, which provides a reasonable mechanism for the
      enhanced visible-light photocatalytic activity of La/N codoped TiO(2) anatase.
      This knowledge may aid the further design and construction of new effective
      visible-light photocatalysts.

PMID- 22401141
TI  - Open quantum system approach to the modeling of spin recombination reactions.
AB  - In theories of spin-dependent radical pair reactions, the time evolution of the
      radical pair, including the effect of the chemical kinetics, is described by a
      master equation in the Liouville formalism. For the description of the chemical
      kinetics, a number of possible reaction operators have been formulated in the
      literature. In this work, we present a framework that allows for a unified
      description of the various proposed mechanisms and the forms of reaction
      operators for the spin-selective recombination processes. On the basis of the
      concept that master equations can be derived from a microscopic description of
      the spin system interacting with external degrees of freedom, it is possible to
      gain insight into the underlying microscopic processes and  develop a systematic
      approach toward determining the specific form of the reaction operator in
      concrete scenarios.

PMID- 22401139
TI  - A systematic review of exercise training to promote locomotor recovery in animal
      models of spinal cord injury.
AB  - In the early 1980s experiments on spinalized cats showed that exercise training
      on the treadmill could enhance locomotor recovery after spinal cord injury (SCI).
      In this review, we summarize the evidence for the effectiveness of exercise
      training aimed at promoting locomotor recovery in animal models of SCI. We
      performed a systematic search of the literature using Medline, Web of Science,
      and Embase. Of the 362 studies screened, 41 were included. The adult female rat
      was the most widely used animal model. The majority of studies (73%) reported
      that exercise training had a positive effect on some aspect of locomotor
      recovery. Studies employing a complete SCI were less likely to have positive
      outcomes. For incomplete SCI models, contusion was the most frequently employed
      method of lesion induction, and the degree of recovery depended on injury
      severity. Positive outcomes were associated with training regimens that involved
      partial weight-bearing activity, commenced within a critical period of 1-2 weeks
      after SCI, and maintained training for at least 8 weeks. Considerable
      heterogeneity in training paradigms and methods used to assess or quantify
      recovery was observed. A 13-item checklist was developed and employed to assess
      the quality of reporting and study design; only 15% of the studies had high
      methodological quality. We recommend that future studies include control groups,
      randomize animals to groups, conduct blinded assessments, report the extent of
      the SCI lesion, and report sample size calculations. A small battery of objective
      assessment methods including assessment of over-ground stepping should also be
      developed and routinely employed. This would allow future meta-analyses of the
      effectiveness of exercise interventions on locomotor recovery.

PMID- 22401142
TI  - per-Hydroxylated pillar[6]arene: synthesis, X-ray crystal structure, and host
      guest complexation.
AB  - A per-hydroxylated pillar[6]arene was prepared. Single-crystal X-ray analysis
      demonstrated that its molecules are arranged in an up-to-down manner to form
      infinite channels in the solid state. Its host-guest complexation with a series
      of bispyridinium salts in solution was further investigated. It was found that
      the per-hydroxylated pillar[6]arene could form a 1:1 complex with paraquat in
      acetone with an association constant of 2.2 * 10(2) M(-1). This complex is a
      [2]pseudorotaxane as shown by its crystal structure, which is the first
      pillar[6]arene-based host-guest complex crystal structure.

PMID- 22401143
TI  - Enzymatic method for measuring starch gelatinization in dry products in situ.
AB  - An enzymatic method based on hydrolysis of starch by amyloglucosidase and
      measurement of d-glucose released by glucose oxidase-peroxidase was developed to
      measure both gelatinized starch and hydrolyzable starch in situ of dried starchy
      products. Efforts focused on the development of sample handling steps (particle
      size reduction of dry samples followed by a unique mechanical resolubilization
      step) prior to the enzymatic hydrolysis using native and fully gelatinized flours
      of corn and rice. The new steps, when optimized, were able to maximize
      resolubilization of gelatinized/retrograded starch while minimizing
      solubilization of native starch in dried samples, thus effectively addressing
      issues of insusceptibility of retrograded starch and susceptibility of native
      starch to enzymatic attacks and eliminating the need to isolate starch from dry
      samples before using an enzymatic method. Various factors affecting these and
      other steps were also investigated, with the objectives to simplify the
      procedures and reduce errors. Results are expressed as the percentage of the
      total starch content. The proposed method, verified by measuring mixed samples of
      native and fully gelatinized flours of five grain species (corn, rice, barley,
      oat, and wheat) at different ratios, is simple, accurate, and reliable, with a
      relative standard deviation of less than 5%.

PMID- 22401144
TI  - Biosimilar medicines in oncology: single-center experience with biosimilar G-CSF.
AB  - AIMS: A biosimilar medicine is one with proven similarity to a reference
      biological product for which the patent has expired and whose active ingredient
      is produced or derived from a living organism. Recombinant granulocyte colony
      stimulating growth factors (G-CSF) are used for the prophylaxis of febrile
      neutropenia. MATERIALS & METHODS: In this observational, single-center study, a
      total of 48 patients with solid tumors were treated with a new biosimilar G-CSF
      (Zarzio((r))) for 4-14 days from the day following the end of chemotherapy.
      RESULTS: Between October 2010 and July 2011, biosimilar G-CSF was administered as
      primary prophylaxis in 37 patients and as secondary prophylaxis in 11 patients in
      our clinic. The median length of G-CSF administration was 7 days (range: 1-12
      days). Three cases of febrile neutropenia were reported: two in patients with
      prostate adenocarcinoma and one in a patient with pulmonary squamous cell
      carcinoma and multiple secondary skeletal lesions. These patients were treated
      with antibiotics and improved within 24 h without the need for hospitalization.
      Nonfebrile grade 4 neutropenia was observed in a further six patients.
      CONCLUSION: Our experience indicates that the use of biosimilar G-CSF is safe and
      effective at reducing neutropenic complications in patients with solid tumors and
      may be associated with cost savings.

PMID- 22401145
TI  - Improved mass defect model for theoretical tryptic peptides.
AB  - Improvements in the mass accuracy and resolution of mass spectrometers have
      greatly aided mass spectrometry-based proteomics in profiling complex biological
      mixtures. With the use of innovative bioinformatics approaches, high mass
      accuracy and resolution information can be used for filtering chemical noise in
      mass spectral data. Using our recent algorithmic developments, we have generated
      the mass distributions of all theoretical tryptic peptides composed of 20 natural
      amino acids and with masses limited to 3.5 kDa. Peptide masses are distributed
      discretely, with well-defined peak clusters separated by empty or sparsely
      populated trough regions. Accurate models for peak centers and widths can be used
      to filter peptide signals from chemical noise. We modeled mass defects, the
      difference between monoisotopic and nominal masses, and peak centers and widths
      in the peptide mass distributions. We found that peak widths encompassing 95% of
      all peptide sequences are substantially smaller than previously thought. The
      result has implications for filtering out larger stretches of the mass axis. Mass
      defects of peptides exhibit an oscillatory behavior which is damped at high mass
      values. The periodicity of the oscillations is about 14 Da which is the most
      common difference between the masses of the 20 natural amino acids. To determine
      the effects of amino acid modifications on our findings, we examined the mass
      distributions of peptides composed of the 20 natural amino acids, oxidized Met,
      and phosphorylated Ser, Thr, and Tyr. We found that extension of the amino acid
      set by modifications increases the 95% peak width. Mass defects decrease,
      reflecting the fact that the average mass defect of natural amino acids is larger
      than that of oxidized Met. We propose that a new model for mass defects and peak
      widths of peptides may improve peptide identifications by filtering chemical
      noise in mass spectral data.

PMID- 22401146
TI  - Moving instead of asking? Performance-based tests and BASFI-questionnaire measure
      different aspects of physical function in ankylosing spondylitis.
AB  - INTRODUCTION: Ankylosing Spondylitis (AS) is characterised by limitations in
      physical function. The Bath Ankylosing Spondylitis Functional Index (BASFI) is
      considered to be the gold-standard to assess physical function in AS patients.
      However, the BASFI questionnaire is a self-reported outcome measure and
      susceptible to subjective interpretation (under- or over-estimation). More
      objective outcome measures, like performance-based tests, could provide an
      objective outcome measurement for the evaluation of limitations in physical
      function. Therefore, the primary aim of this study was to determine the
      association between performance-based measures and the BASFI questionnaire.
      METHODS: In this cross-sectional study 126 AS patients completed the BASFI
      questionnaire and eight performance-based tests based on BASFI-items. Each test
      received three scores: one for performance (time or points) and a score for
      exertion and pain experienced during performance (using modified Borg-scale and
      VAS 0-100 mm, respectively). Linear regression analyses were used to assess the
      associations between the BASFI questionnaire and performance-based tests.
      RESULTS: The univariable association between performance and BASFI-score was
      moderate with a R-square of 0.31 and Beta of 0.56 (p's < 0.05). In a
      multivariable analysis, the association between performance, exertion and pain on
      the one hand and BASFI-score on the other was assessed; R-square increased to
      0.54: the Beta's for exertion and pain during performance were 0.38 and 0.26,
      respectively; the Beta for performance decreased to 0.19 (p's < 0.05).
      CONCLUSIONS: This study demonstrates that alongside actual performance, patients
      seem to incorporate exertion and pain in their assessment of perceived physical
      function on the BASFI questionnaire. Performance-based tests could provide an
      objective outcome measurement for the evaluation of physical function and give
      relevant new information in addition to the BASFI questionnaire.

PMID- 22401147
TI  - Analysis of the current situation regarding the aging rural population in China
      and proposed countermeasures.
AB  - China has become a country with an aging population. Compared with the aged in
      urban areas, the aged in rural areas have low income and are subject to social
      security deficiencies; the oldest among them are the most vulnerable group. If an
      effective mechanism for handling health risk is not available, the poor health of
      the rural elderly will cause an increase in their poverty level, which in turn
      will cause their health to become worse. Therefore, it is essential to analyze
      the current situation regarding rural population aging in China and to develop
      countermeasures. Data from 4 national health services surveys were used to
      analyze the differences between urban and rural populations. The results of the
      analysis revealed that the aged population in rural areas has poor health;
      economic security for the aged population is insufficient; and resources for the
      aged are lacking in rural areas. The Chinese government should improve medicare
      for the aged in rural areas, and establish a medical treatment subsidy system and
      a medical support system for the aged in rural areas.

PMID- 22401148
TI  - The business case for a diabetes self-management intervention in a community
      general hospital.
AB  - There is a growing and increasingly compelling body of evidence that self
      management interventions for persons with type 2 diabetes can be both effective
      and cost-effective from a societal perspective. Yet, the evidence is elusive that
      these interventions can produce a positive business case for a sponsoring
      provider organization in the short term. The lack of a business case limits the
      enthusiasm for provider organizations to implement these proven quality-enhancing
      interventions more widely. This article provides a case example of a self
      management intervention in a community general hospital targeting an underserved
      population who have significant barriers to receiving regular health care. The 3
      component program sought to improve meaningful access to care, increase health
      literacy related to type 2 diabetes, and partner with the enrollees to make long
      term lifestyle changes. The intervention not only resulted in significant
      improvements in HbA1c levels (-0.77%) but saved the hospital an average of $551
      per active patient per year, primarily by reducing hospital visits. With only 255
      actively enrolled patients, the hospital can recover fully its total direct
      annual personnel and operating costs for the program. Because the program serves
      patients who would have been seen at other hospitals, it also enhanced care
      quality and reduced costs for the broader community in which the program is
      embedded.

PMID- 22401149
TI  - Patients with type 2 diabetes benefit from primary care-based disease management:
      a propensity score matched survival time analysis.
AB  - This study aimed to assess the impact of a nationwide German diabetes mellitus
      disease management program (DMP) on survival time and costs in comparison to
      routine care. The authors conducted a retrospective observational cohort study
      using routine administration data from Germany's largest sickness fund to
      identify insured suffering from diabetes in 2002. A total of 95,443 insured with
      type 2 diabetes mellitus who were born before January 1, 1962 met the defined
      inclusion criteria, resulting in 19,888 pairs of DMP participants and
      nonparticipants matched for socioeconomic and health status using propensity
      score matching methods. This is the first time propensity score matching has been
      used to evaluate a survival benefit of DMPs. In the time frame analyzed (3
      years), mean survival time for the DMP group was 1045 days vs. 985 days for the
      routine care group (P<0.001). Mean daily hospital and total costs (including DMP
      administration and medical costs) were lower for the DMP group in the case of
      deceased insureds (92? vs. 139? and 122? vs. 169?, respectively) as well as for
      censored observations (6? vs. 7? and 12.9? vs. 13.4?, respectively). Mean daily
      drug costs were slightly lower for deceased insured in the DMP group (difference
      0.6?), while no identifiable difference was found for censored observations. In
      this study, insured who were enrolled in a DMP for diabetes mellitus in the
      German Statutory Health Insurance showed a significant benefit in survival time.
      They also incurred lower costs compared to propensity score matched insured in
      routine care.

PMID- 22401150
TI  - Burden of illness for an employed population with chronic obstructive pulmonary
      disease.
AB  - Chronic obstructive pulmonary disease (COPD) affects approximately 7% of
      Americans. COPD impacts productivity and forces 1 in 5 employees ages 45-65 years
      old to retire prematurely. Our objective was to quantify the direct and indirect
      costs of COPD in an employed population in the United States. A retrospective
      analysis using Thomson Reuters MarketScan commercial claims and Health and
      Productivity (HPM) databases (2000-2007) identified employees (ages 18-65 years)
      with >= 1 COPD medical claim, >= 6 month insurance eligibility pre and >= 12
      months post diagnosis, and >= 12 months HPM data post diagnosis. COPD subjects
      were matched to non-COPD subjects using propensity scores to create a comparison
      group with similar characteristics. Differences in medical and pharmacy
      utilization and productivity (absence and short-term disability [STD] days) were
      examined using negative binomial regression, and cost differences using Heckman
      selection models. A total of 27,612 COPD patients were matched in a 1:1 ratio to
      825,884 non-COPD patients; 80% were ages 36-65 years, and 59% were male. COPD
      employees had about twice the rate of emergency department visits and
      hospitalizations compared to non-COPD employees (P<0.0001). The rate of absence
      and STD days was approximately 1.5 times higher (P<0.0001) compared to non-COPD
      employees. Yearly direct and indirect expenditures were higher ($3609 and $909,
      respectively; P<0.0001) for COPD versus non-COPD employees. Excess utilization
      and associated costs of COPD to employers was quantified. By understanding these
      costs, employers may evaluate disease management programs and treatment to
      improve outcomes for employees with COPD. Improved treatment options may reduce
      the direct and indirect costs of COPD.

PMID- 22401151
TI  - Disparity of risk-adjusted inpatient outcomes among African American and white
      patients hospitalized with community-acquired pneumonia.
AB  - The objectives of this study were to examine the associations between inpatient
      pneumonia outcomes, health care factors, and sociodemographics with an emphasis
      on race. African American and white patients from the 2008 National Hospital
      Discharge Survey who were admitted to nonprofit and for-profit hospitals with a
      principal diagnosis of pneumonia were sampled (n=1924). Three outcomes were
      measured: length of hospital stay, discharge to home, and deceased at discharge.
      Length of hospital stay was measured with negative binomial regression including
      incidence rate ratios (IRRs), while the remaining 2 outcomes were measured with
      logistic regression including odds ratios (ORs). Patients with longer hospital
      stays relative to peers were likely older (IRR=1.01, 95% confidence interval
      [CI]=1.01-1.01, P<0.001) and African American (IRR=1.19, 95% CI=1.10-1.30,
      P<0.001), but had fewer comorbidities (IRR=0.97, 95% CI=0.94-0.99, P=0.016).
      Patients were less likely to be discharged to home if they were older (OR=0.96,
      95% CI=0.95-0.96, P<0.001), African American (OR=0.68, 95% CI=0.52-0.90,
      P=0.006), and had government insurance (OR=0.59, 95% CI=0.44-0.79, P<0.001).
      Patients deceased at discharge were more likely to be older (OR=1.03, 95% CI=1.01
      1.05, P=0.001), African American (OR=1.97, 95% CI=1.10-3.53, P=0.023), and to
      have fewer comorbidities (OR=0.71, 95% CI=0.57-0.88, P=0.002). African Americans
      with pneumonia experience inequitable inpatient pneumonia-related outcomes
      relative to whites. Hospital interventions addressing equity are needed.

PMID- 22401152
TI  - Medication adherence among recipients with chronic diseases enrolled in a state
      Medicaid program.
AB  - Limited information is currently available about medication adherence for common
      chronic conditions among the Medicaid population. The primary objective of this
      study was to assess medication adherence among Medicaid recipients with
      depression, diabetes, epilepsy, hypercholesterolemia, and hypertension. Factors
      influencing adherence were determined. The authors also assessed whether
      adherence influences the utilization of acute care services. The target
      population included nonelderly adult recipients (ages 21-64 years) who were
      continuously enrolled in the Mississippi (MS) Medicaid fee-for-service program
      from January 1, 2006 to December 31, 2007. Recipients were identified who had a
      medical services claim with a diagnosis of depression, diabetes, epilepsy,
      hypercholesterolemia, or hypertension in calendar year 2006. Within each chronic
      disease sample, medication adherence was determined using calendar year 2007 data
      for recipients who met inclusion and exclusion criteria. Recipients with
      adherence >=80% were classified as adherent. Logistic regression analyses were
      used to determine the factors that predict medication adherence and the effect of
      adherence on concurrent all-cause acute care service (ie, hospitalization,
      emergency room visit) utilization. Approximately 24% of recipients with
      depression, 35.9% with diabetes, 53.6% with epilepsy, 32% with
      hypercholesterolemia, and 42.2% with hypertension were adherent. Within each
      chronic disease sample, males and whites had higher adherence than females and
      blacks. After controlling for demographic and disease-related covariates,
      recipients who were adherent had lower concurrent acute care service utilization
      than nonadherent recipients. Given the inverse relationship between adherence and
      acute care service utilization, policy makers should consider implementing
      educational interventions aimed at improving adherence in this underprivileged
      population.

PMID- 22401154
TI  - [Severe sepsis: to reconsider the pathogenesis and the therapies].

PMID- 22401153
TI  - Misperceptions of medicaid ineligibility persist among African American
      caregivers of Alzheimer's dementia care recipients.
AB  - African American caregivers of the elderly, including those who care for patients
      with Alzheimer's and other forms of dementia, remain underserved by Medicaid
      Assistance Programs. The purpose of this exploratory study was to ascertain to
      what degree participants in an Alzheimer's Association program that primarily
      targeted African Americans applied for and received Medicaid assistance, in
      particular for adult day care, in-home care, and respite care. Secondary data
      from the Delaware Regional Office of the Alzheimer's Association's 2006 Caregiver
      Survey of 38 caregivers were reviewed using descriptive, chi-square, and logistic
      regression analysis. Results indicate that 20 caregivers applied for Medicaid
      services, 12 of whom were approved. However, 18 caregivers did not apply for
      Medicaid mainly because they perceived that they would not qualify for benefits,
      without investigating their eligibility. Clearly more education is needed in
      African American communities about the eligibility requirements and benefits of
      Medicaid Assistance Programs because services such as adult day care, in-home
      care, and respite care have been shown to reduce some of the burden, stress, and
      strain associated with caring for elderly patients with Alzheimer's dementia.
      However, a multisystem approach should be used in the outreach and education
      processes. Finally, the Medicaid application process should be streamlined to
      make it less cumbersome. More financial and support services are needed by
      African American caregivers of Alzheimer's care recipients.

PMID- 22401155
TI  - [A new strategy of fighting against the bacterial infection disease].

PMID- 22401156
TI  - [Prognostic value of D-dimer in patients with sepsis in emergency department: a
      prospective study].
AB  - OBJECTIVE: To investigate the value of the concentration of D-dimer in predicting
      28-day mortality of sepsis patients in emergency department in order to determine
      its prognostic values. METHODS: A prospective study was conducted. A total of 766
      sepsis patients treated in the emergency department of Beijing Chaoyang Hospital
      of the Capital Medical University from October 2009 to July 2010 were enrolled,
      and admission blood samples were obtained for D-dimer measurement (solid phase
      immune chromatography). A variety of clinical and laboratory variables were
      recorded. With 28 days as end point, the D-dimer levels, acute physiology and
      chronic health evaluation II (APACHEII) score, and simplify acute physiology
      score II (SAPSII) were compared respectively between survivors and non-survivors.
      The status of each patient was ascertained, and the association between the
      concentration of D--dimer and 28-day mortality was assessed. RESULTS: Two hundred
      and thirty-three patients died during the 28--day observation period among 766
      patients. D--dimer concentration (MUg/L) among deceased were significantly higher
      than those of survivors [1220.0 (789.0, 1835.0) vs. 323.0 (158.0, 642.0), P <
      0.01]. The level of D-dimer showed positive correlation with APACHEII score and
      SAPSII [r1=0.643, r2=0.632, both P < 0.01]. D-dimer concentration had an area
      under the receiver operating characteristic (ROC) curve (AUC) of 0.880 for
      predicting 28-day mortality, with 95% confidence interval (95%CI) 0.855-0.904, P
      < 0.001; the optimal D-dimer cut point for predicting 28-day mortality was 663.5
      MUg/L. D--dimer concentration higher than 663.5 MUg/L, APACHEII score higher than
      19.5 and SAPSII higher than 39.5 were the independent predictors of 28-day
      mortality [odds ratio (OR): 17.5, 15.7, 19.6, all P < 0.001]. The 28-day
      mortality (1.4%, 12.3%, 64.2%), APACHEII score [11 (9, 13), 13 (11, 16), 19 (15,
      22)] and SAPSII [24 (18, 29), 31 (24, 36), 40 (33, 49)] showed statistically
      significant among D--dimer <250.0, 250.0--663.5, >663.5 MUg/L three groups (all P
      < 0.01). CONCLUSIONS: D-dimer concentration is an independent predictor of 28-
      day mortality in patients with sepsis. D--dimer level shows a high predictive
      value in patients with sepsis, similar to APACHE II score and SAPSII. It can be
      helpful in risk stratification in septic patients.

PMID- 22401157
TI  - [Effect of interleukin-10 level and human leukocyte antigen-DR expression as
      prognostic predictors in critically ill patients undergoing continuous renal
      replacement therapy].
AB  - OBJECTIVE: To inquire into interleukin-10 (IL--10) level and monocyte expression
      of human leukocyte antigen--DR (HLA--DR) are predictors of infection and
      prognosis in critically ill patients undergoing continuous renal replacement
      therapy (CRRT). METHODS: A total of 43 critically ill patients undergoing
      continuous veno-venous hemofiltration (CVVH) were recruited from the intensive
      care unit (ICU). Anti--coagulated blood was obtained at 1 day before and 4 days
      after undergoing CVVH, and plasma IL--10 level (enzyme linked immunosorbent
      assay) and HLA--DR expression (flow cytometry) were determined. Thirty healthy
      subjects were enrolled as controls. In addition, the correlation between IL--10
      and acute physiology and chronic health evaluation II (APACHEII) score was
      assessed. RESULTS: (1)Altogether, 7 patients died among a total of 43 critically
      ill patients, the mortality was 16.3%. Eighteen patients had negative cultures
      during the study (group I), and 19 patients had positive cultures (group II), and
      in 6 patients positive bacterial culture appeared 72 hours after the beginning of
      the treatment (group III). (2) The IL--10 level (ng/L) was higher in patients
      than in healthy subjects [23.46 (46.71) vs. 0.32 (0.45), P < 0.01]. Compared with
      group I, the levels of IL--10 in group II and III were higher significantly
      [40.20 (46.44), 41.78 (49.63) vs. 7.33 (21.05), both P < 0.05]. Continuous
      observation revealed that IL--10 rapidly lowered in group I after treatment [4.50
      (7.44) vs. 7.33 (21.05), P < 0.05], while there was no apparent change in
      patients of other two groups. It was found that IL--10 was significant positive
      correlation with the APACHEII score (r = 0.71, P < 0.01).(3) HLA--DR was lower in
      patients than in healthy individuals [21.65% (25.62%) vs. 90.39% (9.80%), P <
      0.01]. After CVVH, HLA--DR expression was obviously increased in group I [64.95%
      (35.03%) vs. 32.45% (45.03%), P < 0.01]. However, there were no significant
      changes in the other two groups. The patients who died had persistent and
      extremely low HLA--DR expression. CONCLUSIONS: (1)A significant discriminative
      power of IL--10 levels in predicting disease severity was found among the
      patients receiving CRRT, and persistently high IL--10 level predicts poor
      prognosis. (2) Persistently low monocyte HLA--DR expression may indicate
      concomitant or impending infection in patients receiving CRRT.

PMID- 22401158
TI  - [Pharmacokinetics of meropenem administered with prolonged infusion time in
      patients receiving continuous veno-venous hemofiltration].
AB  - OBJECTIVE: To demonstrate the pharmacokinetic profile of meropenem when
      administered by 3-hour infusion in patients undergoing continuous veno-venous
      hemofiltration (CVVH). METHODS: The study was conducted in 10 patients, who were
      treated with CVVH. Each subject received meropenem in 3-hour infusion of 500 mg
      every 6 hours. Blood samples were collected before infusion (0 hour) and 0.25,
      0.5, 1, 1.5, 2, 3, 4, 5, 6 hours (just before the infusion of the next dose)
      after the beginning of the fourth infusion. The concentrations of meropenem in
      plasma were measured by high-performance liquid chromatography method, and mean
      serum meropenem concentration-time curve was plotted. RESULTS: Peak plasma drug
      concentrations measured 3 hours post-infusion were (25.05 +/- 5.64) mg/L, and
      trough levels after 6 hours of infusion were (13.03 +/- 3.01) mg/L. The area
      under the plasma concentration-time curve (AUC) was (118.42 +/- 26.78) mg x h-1 x
      L-2. The elimination half-life (T1/2) was (3.74 +/- 0.55) hours. The mean
      residence time (MRT) was (4.99 +/- 0.84) hours. The volume of distribution (Vb)
      was (22.85 +/- 9.85) L and clearance of meropenem (CL) was (4.49 +/- 1.32) L/h.
      The percentage of time that the serum drug concentration was above the minimum
      inhibitory concentration (MIC) accounting for the interval time of infusion
      (%T>MIC) was 100% (MIC 8 mg/L) in all the 10 patients. CONCLUSION: Based on these
      data, we concluded that satisfactory pharmacodynamic parameters could be attained
      in CVVH patients treated with meropenem by a prolonged infusion time of 3 hours
      with a dosage of 500 mg for every 6 hours.

PMID- 22401159
TI  - [Expression of ubiquitin in the spleen and its influence on the dendritic cell
      immunomodulation function in multiple organ dysfunction syndrome in mice].
AB  - OBJECTIVE: To explore the expression change in ubiquitin (Ub) in the spleen and
      its significance in multiple organ dysfunction syndrome (MODS) in mice, and to
      study the effects of ubiquitination of major histocompatibility complex II
      (MHCII) on the activity and immunomodulation function of splenic dendritic cell
      (DC). METHODS: Two hundred and ten mice were divided into the normal control
      group (n = 30) and MODS group (n = 180) according to the method of random digital
      table, and MODS model was replicated by intraperitoneal injection of zymosan. The
      MODS group mice were further divided evenly into 6, 12, 24, 48-hour and 5-7-day
      and 10-12-day groups. Ub protein and expression of CD11c+DC and MHCII molecule I
      A(b) were examined using immunohistochemistry and immunofluorescence methods. Ub
      mRNA expression in the spleen was measured by real-time quantitative reverse
      transcription--polymerase chain reaction (RT-PCR). RESULTS:
      (1)Immunohistochemistry results showed: the number of Ub positive cells in the
      spleen increased significantly at 6 hours in MODS group compared with that of the
      normal control group, and it reached the peak at 24 hours [(16.83 +/- 0.38)% vs.
      (8.60 +/- 0.86)%, P < 0.05] and then decreased gradually. At 10-12 days, the
      number of Ub positive cells decreased significantly compared with that of the
      normal control group [(4.66 +/- 0.34)% vs. (8.60 +/- 0.86)%, P < 0.05]. (2)RT-PCR
      results displayed: compared with normal control group, Ub mRNA expression in
      spleen increased at 6 hours in MODS group, and it reached the peak at 24 hours
      (2.17 +/- 0.20 vs. 1.00 +/- 0.00, P < 0.01). Then, it decreased gradually. At 10
      12 days, Ub mRNA decreased significantly as compared with that of normal control
      group (0.72 +/- 0.08 vs. 1.00 +/- 0.00, P < 0.05). (3)Immunofluorescence results
      displayed: compared with normal control group, CD11c+DC increased significantly
      at 6 hours in MODS group and reached the peak at 24 hours [(7.55 +/- 0.04)% vs.
      (2.08 +/- 0.13)%, P < 0.05], and then it decreased gradually. At 10-12 days, it
      was close to that of the normal control group [(2.28 +/- 0.06)% vs. (2.08 +/-
      0.13)%, P>0.05]. Compared with the normal control group, I-A(b) positive cells in
      the spleen was significantly increased at 6 hours in MODS group [(10.90 +/-
      1.40)% vs. (5.78 +/- 0.47)%, P < 0.01], but it decreased at 24 hours [(3.32 +/-
      0.91)% vs. (5.78 +/- 0.47)%, P < 0.05]. I-A(b) positive cells were restored to
      the normal level at 48 hours and 5--7 days, and decreased significantly again at
      10-12 days [(2.20 +/- 0.97)% vs. (5.78 +/- 0.47)%, P < 0.05]. The number of Ub
      positive cells correlated positively to the expression of I-A(b) and the CD11c
      [r1 = 0.899, r2=0.987, both P < 0.05]. CONCLUSIONS: Ub might influence the
      maturation and activation of DC via ubiquitination of the MHCII molecule on DC,
      thereby influencing the immune response at different stages of MODS. The result
      might provide a new way to recognize immune response and also a new monitoring
      index for immune response regulation.

PMID- 22401160
TI  - [The clinical significance of determining the severity and prognosis by
      monitoring the changes in sublingual microcirculation in patients with severe
      sepsis].
AB  - OBJECTIVE: To investigate the clinical significance of dynamic monitoring of
      changes in the sublingual microcirculation in patients with severe sepsis to
      determine the degree of severity of the clinical condition and prognosis.
      METHODS: A prospective study was conducted. Sixty--five patients in the intensive
      care unit (ICU) in Beijing Friendship Hospital were enrolled from June 2010 to
      December 2010, among whom there were 30 cases of sepsis, 35 cases of severe
      sepsis. The severe sepsis patients received the early goal--directed
      resuscitation; and at 0 (before treatment), 6, 12, 24, 48, 72 hours after
      resuscitation, the technology of sidestream dark--field was used to measure the
      sublingual total vessel density (TVD), perfusing vessel density (PVD), proportion
      of perfused vessels (PPV), microvascular flow index (MFI) of sublingual
      microcirculation in patients and acute physiology and chronic health evaluation
      II (APACHEII) score, ICU days and 28--day mortality were recorded. Thirty healthy
      individuals were enrolled as the control group. RESULTS: The sublingual PPV and
      MFI were significantly lower in sepsis patients than those of the control group
      [PPV: (73.60 +/- 16.77)% vs. (85.17 +/- 7.60)%; MFI: 3.23 +/- 0.77 vs. 3.78 +/-
      0.35, both P < 0.05]; PVD, PPV, MFI in severe sepsis patients were not only
      significantly lower than those of the sepsis group {PVD[mm/mm2]: 7.53 +/- 4.38
      vs.12.15 +/- 2.88; PPV: (49.13 +/- 33.74)% vs. (73.60 +/- 16.77)%; MFI: 2.21 +/-
      1.41 vs. 3.23 +/- 0.77, all P < 0.05}. After the early goal--directed fluid
      resuscitation, the sublingual microcirculation was improved significantly
      compared with that before treatment (0 hour), and they were remarkably apparent
      at 12 hours {TVD[mm/mm2]: 5.76 +/- 2.25 vs. 6.72 +/- 4.37; PVD [mm/mm2]: 7.57 +/-
      1.77 vs. 5.48 +/- 4.39; PPV:(69.47 +/- 19.24)% vs. (34.55 +/- 30.82)%; MFI: 3.17
      +/- 0.49 vs. 1.55 +/- 1.14, all P < 0.05}. Compared with the sepsis group,
      APACHEII score of the severe sepsis group was elevated (24.77 +/- 7.45 vs. 19.30
      +/- 10.36, but P>0.05), the length of stay in ICU (days) was longer (20.60 +/-
      19.87 vs. 10.33 +/- 9.53, P < 0.05), and the 28--day mortality was higher (45.71%
      vs. 36.36%, but P>0.05). In the severe sepsis group, compared with the survival
      group (19 cases), the sublingual microcirculation in the non-survival group (16
      cases) PVD, PPV, MFI were significantly decreased{PVD[mm/mm2]:6.70 +/- 5.15 vs.
      8.53 +/- 3.13; PPV: (44.23 +/- 37.71)% vs. (54.96 +/- 28.41)%; MFI: 1.89 +/- 1.65
      vs. 2.58 +/- 0.98, P < 0.05 or P < 0.01}, but APACHEII score and length of stay
      in ICU (days) were not significantly different (23.19 +/- 6.46 vs. 20.31 +/-
      6.03; 16.13 +/- 10.90 vs. 19.19 +/- 9.90, both P > 0.05). Correlation analysis
      showed that: PPV showed a significant negative correlation with the prognosis of
      the patients (r = -0.374, P < 0.05). CONCLUSION: Sequential monitoring of the
      sublingual microcirculation in patients with severe sepsis can be used to
      determine the disease severity, and to forecast the outcome of the patient.

PMID- 22401161
TI  - [Analysis of the risk factors related to prognosis of severe intra-abdominal
      infection in surgical intensive care unit].
AB  - OBJECTIVE: To   investigate   the   risk   factors   related   to  prognosis   of
      patients   with   severe intra-abdominal infection (SIAI) in surgical intensive
      care unit (SICU). METHODS: Clinical data of 69 patients with SIAI, who were
      hospitalized during January 2008 and April 2011 in SICU, were analyzed
      retrospectively. According to the outcome at discharge from SICU, 69 patients
      were divided into two groups: the survivors 42 cases; the deceased 27 cases. The
      potential risk factors of SIAI patients in SICU were analyzed by univariate
      analysis and logistic regression analysis. RESULTS: Univariate analysis showed
      that average acute physiology and chronic health evaluation II (APACHEII) scores
      (the survival group: 11.76 +/-  3.48; the death group: 17.12 +/-  4.50),
      inadequate treatment of intra-abdominal infection (3 survivors, 21 deceased),
      inadequate initial antibiotic treatment (3 survivors, 15 deceased) and septic
      shock (24 survivors, 27 deceased) were risk factors for mortality (all P < 0.01).
      Logistic regression analysis showed that average APACHEII scores over 15
      [relative risk (RR): 6.846, P value: 0.044] and insufficient treatment of intra
      abdominal infection (RR: 21.319, P value: 0.018) were the independent risk
      factors in SIAI patients in SICU. CONCLUSION: To decrease the mortality of SIAI
      patients in SICU, more attention should be paid to monitor APACHEII scores and to
      handle intra-abdominal infection adequately.

PMID- 22401162
TI  - [Effects of Notch signaling pathway and vascular endothelial growth factor gene
      on the functions of endothelial cells derived from rat bone marrow mesenchymal
      stem cells].
AB  - OBJECTIVE: To explore the effects of Notch signaling pathway and the vascular
      endothelial growth factor [VEGF(165)] gene on the functions of endothelial cells
      derived from rat bone marrow mesenchymal stem cells (MSCs). METHODS: Isolated and
      cultivated rat bone marrow MSCs in vitro, then the cells were treated by VEGF165
      and basic fibroblast growth factor (bFGF) for 2 weeks to induce them to
      differentiate into endothelial cells. The gene of VEGF165 was transfected into
      differentiated endothelial cells to promote the functions of the cells. The
      receptor Notch1 and the ligand Jagged1 of the Notch signaling were detected by
      reverse transcription-polymerase chain reaction (RT-PCR) before and after the
      transfection. gamma-secretase inhibitor L-685458 was used to block Notch pathway.
      Migration ability of cells was detected by scarification test. Cells were
      inoculated on semisolid gel to study their ability of forming capillary-like
      structure. RESULTS: After transfection, VEGF165 mRNA could be detected on the
      differentiated endothelial cells. The expression of Jagged1 mRNA was up
      regulated(1.08 +/- 0.01 vs. 1.01 +/- 0.02,P < 0.01) and there was no change in
      Notch1 mRNA(0.60 +/- 0.02 vs. 0.59 +/- 0.01,P > 0.05). The ability of migration
      was enhanced (number of cells on the scratched area:46.45 +/- 4.46 vs. 41.61 +/-
      1.42,P < 0.05), and the ability of forming capillary-like structure on semisolid
      gel showed no change (cells classification: 3.00 +/- 0.89 vs. 2.00 +/- 0.89,P >
      0.05). After the transfection, using the gamma-secretase inhibitor L-685458 to
      block the Notch signaling transduction, the ability of migration of the
      differentiated endothelial cells (number of cells on the scratched area: 51.72 +/
      3.47 vs. 46.45 +/- 4.46,P < 0.05), and that of forming capillary--like structure
      (cells classification: 4.17 +/- 0.75 vs. 3.00 +/- 0.89, P < 0.05), was also
      further enhanced. CONCLUSION: Transfection of the gene of VEGF165 into the
      differentiated endothelial cells can reinforce the function of these cells, and
      when Notch signaling was blocked, this effect can be further amplified.

PMID- 22401163
TI  - [Clinical analysis of linezolid in treatment of infection with methicillin-
      resistant Staphylococcus in 14 neurosurgical patients].
AB  - OBJECTIVE: To evaluate the efficacy and safety of linezolid in the treatment of
      post-neurosurgical intracranial methicillin-resistant Staphylococcus (MRS)
      infection. METHODS: The data from 14 patients, admitted to neurological intensive
      care unit (ICU) of Medical College of Chinese People's Armed Police Forces
      between March 2009 and November 2011, were retrospectively analyzed. All these
      cases suffered from post-neurosurgical intracranial infection by MRS and received
      linezolid treatment. Blood and cerebrospinal fluid (CSF) were collected before
      and 7 days and 14 days after treatment for routine and bacteriological
      examinations to assess clinical efficacy and adverse reactions of linezolid.
      RESULTS: After 14-day treatment with linezolid, the clinical and laboratory
      parameters showed significant improvement: glucose (mmol/L) in CSF rose from 1.00
      (0.65) to 3.15 (1.60), protein (mg/L) in CSF dropped from 2238.50 (2072.50) to
      606.50 (217.30), white blood cell count [*106/L] in CSF fell from 920.00
      (1587.50) to 30.00 (40.00), and the number of patients with CSF neutrophil
      ratio>0.20 was reduced from 14 to 1 (all P < 0.01). In addition, serum
      procalcitonin level (MUg/L) was significantly reduced from 0.65 (1.16) to 0.08
      (0.09) after linezolid therapy (P < 0.01). Total effective rate was 85.7%
      (12/14), and CSF bacterial clearance rate reached 100%. No adverse events were
      found during the treatment. CONCLUSION: Linezolid could effectively control post-
      neurosurgical intracranial MRS infection and alleviate the inflammatory responses
      with safety.

PMID- 22401164
TI  - [Bundle therapy for septic shock in children].

PMID- 22401165
TI  - [Comparison of direct insertion and sheath-avulsion method in the placement of
      cuffed central venous catheter].

PMID- 22401166
TI  - [A new perspective of research into cholinergic anti-inflammatory pathway].

PMID- 22401167
TI  - Self-assembly and catalytic activity of metal nanoparticles immobilized in
      polymer membrane prepared via layer-by-layer approach.
AB  - Densely packed nanoparticles distributed in a stable and robust thin film is a
      highly preferred system for utilizing the various applications of nanoparticles.
      Here, we report covalent bond mediated layer-by-layer (LbL) self-assembled thin
      films of nanoparticles embedded in polymer membrane. Polymer with complementary
      functional group is utilized for fabrication of thin film via covalent bonding.
      UV-visible spectroscopy, atomic force microscopy (AFM) and scanning electron
      microscopy (SEM) were used to monitor the growth of LbL thin film. Subsequently,
      the composite thin film is used for catalysis of an organic electron transfer
      reaction of p-nitrophenol to p-aminophenol by sodium borohydride. The catalytic
      activity of these composite films is assayed multiple times, proving its
      applicability as a catalyst. The kinetic data obtained by monitoring reduction of
      p-nitrophenol suggest that the reaction rates are directly related to the sizes
      of the nanoparticle and porosity of the membrane.

PMID- 22401168
TI  - gamma-Secretase-dependent cleavage of E-cadherin by staurosporine in breast
      cancer cells.
AB  - E-cadherin is a transmembrane protein that serves as a cell adhesion molecule
      component of the adherens junction. We previously showed that cadmium induced
      gamma-secretase-dependent E-cadherin cleavage via oxidative stress. In this
      study, we report that staurosporine (STS)-induced apoptosis induces caspase-2
      and/or -8-dependent E-cadherin cleavage. STS increased gamma-secretase-dependent
      cleavage of E-cadherin in breast cancer cells through caspase activation. The
      ability of the gamma-secretase inhibitor DAPT and the caspase inhibitor zVAD-FMK
      to block E-cadherin cleavage provided support for these results. The cleavage of
      E-cadherin was blocked by caspase-2 and -8 inhibitors. Immunofluorescence
      analysis confirmed that, along with the disappearance of E-cadherin staining at
      the cell surface, the E-cadherin cytoplasmic domain accumulated in the cytosol.
      In the presence of an inhibitor of gamma-secretase or caspase, the cleavage of E
      cadherin was partially blocked. Our findings suggest that activation of caspase
      2/-8 stimulated the disruption of cadherin-mediated cell-cell contacts in
      apoptotic cells via gamma-secretase activation.

PMID- 22401169
TI  - Adoption of new drugs by physicians: a survival analysis.
AB  - BACKGROUND: New drugs often substitute others cheaper and with a risk-benefit
      balance better established. Our aim was to analyse the diffusion of new drugs
      during the first months of use, examining the differences between family
      physicians and specialists. METHODS: Prescription data were obtained of
      cefditoren, duloxetine, etoricoxib, ezetimibe, levocetirizine, olmesartan,
      pregabalin and tiotropium 36 months after their launching. We obtained the
      monthly number of prescriptions per doctor and the number prescribers of each
      drug by specialty. After discarding those with less than 10 prescriptions during
      this period, physicians were defined as adopters if the number of prescriptions
      was over the 25th percentile for each drug and level (primary or secondary care).
      The diffusion of each drug was studied by determining the number of adopter
      family physicians throughout the study period. Among the group of adopters, we
      compared the month of the first prescription by family physicians to that of
      other specialists using the Kaplan-Meier method. RESULTS: The adoption of the
      drugs in primary care follows an exponential diffusion curve that reaches a
      plateau at month 6 to 23. Tiotropium was the most rapidly and widely adopted
      drug. Cefditoren spread at a slower rate and was the least adopted. The diffusion
      of etoricoxib was initially slowed down due to administrative requirements for
      its prescription. The median time of adoption in the case of family physicians
      was 4-6 months. For each of the drugs, physicians of a specialty other than
      family physicians adopted it first. CONCLUSIONS: The number of adopters of a new
      drug increases quickly in the first months and reaches a plateau. The number of
      adopter family physicians varies considerably for different drugs. The adoption
      of new drugs is faster in specialists. The time of adoption should be considered
      to promote rational prescribing by providing timely information about new drugs
      and independent medical education.

PMID- 22401170
TI  - alpha-Thalassemia mutations in two provinces of Southern Iran: Fars & Kohkeloye
      and Bouyer Ahmad.
AB  - The major defect in alpha-thalassemia (alpha-thal) is a single or double gene
      deletion. The aim of this study was to evaluate the alpha-thal mutations in two
      provinces of Southern Iran, Fars & Kohkeloye and Bouyer Ahmad. A total of 2000
      subjects with microcytic hypochromic anemia was selected as a study group;
      finally, 1177 subjects were found to be alpha-thal mutation carriers by gap
      polymerase chain reaction (gap-PCR) protocols and were confirmed by multiplex PCR
      and reverse hybridization test strips. A total of 1195 mutated alpha-globin
      alleles was identified in these patients that includes at least 10 different gene
      mutations. The most common mutation found was -alpha(3.7) (rightward deletion)
      (71.7%) and alpha(-5 nt) (IVS-I, -TGAGG) and the polyadenylation signal site
      (poly A1; AATAAA>AATAAG) were the second and third most common mutations (7.0 and
      4.2%, respectively). In countries like Iran, with a high prevalence of
      thalassemia, identifying different mutations is helpful in carrier screening,
      genetic counseling and prenatal diagnosis of at-risk couples for the prevention
      of the birth of babies affected by severe thalassemic anomalies.

PMID- 22401172
TI  - Lattice mismatch induced nonlinear growth of graphene.
AB  - As a two-dimensional material, graphene can be obtained via epitaxial growth on a
      suitable substrate. Recently, an interesting nonlinear behavior of graphene
      growth has been observed on some metal surfaces, but the underlying mechanism is
      still elusive. Taking the Ir(111) surface as an example, we perform a mechanistic
      study on graphene growth using a combined approach of first-principles
      calculations and kinetic Monte Carlo (kMC) simulations. Small carbon clusters on
      the terrace or at step sites are studied first. Then, we investigate how these
      small carbon species are attached to graphene edges. Generally, attachment of
      carbon atoms is thermodynamically favorable. However, due to substrate effect,
      there are also some edge sites where graphene growth must proceed via cluster
      attachment. The overall growth rate is determined by these cluster attachment
      processes, which have a much lower chance of happening compared to the monomer
      attachment. On the basis of such an inhomogeneous growth picture, kMC simulations
      are performed by separating different time scales, and the experimentally found
      quintic-like behavior is well reproduced. Different nonlinear growth behaviors
      are predicted for different graphene orientations, which is consistent with
      previous experiments. Inhomogeneity induced by lattice mismatch revealed in this
      study is expected to be a universal phenomenon and will play an important role in
      the growth of many other heteroepitaxial systems.

PMID- 22401173
TI  - Structural platform for the autolytic activity of an intact NS2B-NS3 protease
      complex from dengue virus.
AB  - Dengue virus completes its protein synthesis inside human cells on the
      endoplasmic reticulum membrane by processing the single-chain polyprotein
      precursor into 10 functional proteins. This vital process relies on the two
      component virus-encoded protease complex; nonstructural protein 3 (NS3) possesses
      the proteolytic activity in its N-terminus, and NS2B acts as a fundamental
      activator and membrane-anchoring subunit. The membrane-associated NS2B-NS3
      complex has essentially not yet been isolated or studied. We describe here a
      useful protocol for the preparation of the full-length NS2B-NS3 complex from
      dengue serotype 2 virus by utilizing a Mistic-fusion expression cassette in
      Escherichia coli. The protease complex was successfully solubilized and
      stabilized from the bacterial membrane and purified with the use of fos-choline
      14 detergent. The detergent-solubilized protease complex retained autolytic
      activity and, intriguingly, exists as a robust trimer, implying a molecular
      assembly in the membrane. We further conducted a random mutagenesis study to
      efficiently scan for entire residues and motifs contributing to autocleavage and
      provide evidence of the importance of the two distal beta-hairpins in the
      activity of the viral protease. Our results provide the first comprehensive view
      of an active dengue protease in the membrane-bound form.

PMID- 22401171
TI  - NLRC5 knockdown in chicken macrophages alters response to LPS and poly (I:C)
      stimulation.
AB  - BACKGROUND: NLRC5 is a member of the CARD domain containing, nucleotide-binding
      oligomerization (NOD)-like receptor (NLR) family, which recognizes pathogen
      associated molecular patterns (PAMPs) and initiates an innate immune response
      leading to inflammation and/or cell death. However, the specific role of NLRC5 as
      a modulator of the inflammatory immune response remains controversial. It has
      been reported to be a mediator of type I IFNs, NF-kB, and MHC class I gene. But
      no study on NLRC5 function has been reported to date in chickens. In the current
      study, we investigated the role of NLRC5 in the regulation of IFNA, IFNB, IL-6,
      and MHC class I in the chicken HD11 macrophage cell line, by using RNAi
      technology. HD11 cells were transfected with one of five siRNAs (s1, s2, s3,
      negative-siRNA, or a mixture of s1, s2, s3-siRNAs). After 24 hours, cells were
      exposed to LPS or poly (I:C) or a vehicle control. Gene expression of NLRC5,
      IFNA, IFNB, IL-6, and MHC class I at 2, 4, 6, and 8 hours post stimulation (hps)
      was quantified by qPCR. RESULTS: The expression of NLRC5, IFNA, IFNB, and IL-6
      genes in negative irrelevant transfection controls was up-regulated at 2 hps
      after LPS treatment compared to the vehicle controls. S3-siRNA effectively
      knocked down NLRC5 expression at 4 hps, and the expression of IFNA and IFNB (but
      not IL-6 and MHC class I) was also down-regulated at 4 hps in s3-siRNA
      transfected cells, compared to negative irrelevant transfection controls.
      Stimulation by LPS appeared to relatively restore the decrease in NLRC5, IFNA,
      and IFNB expression, but the difference is not significant. CONCLUSIONS:
      Functional characterization of chicken NLRC5 in an in vitro system demonstrated
      its importance in regulating intracellular molecules involved in inflammatory
      response. The knockdown of NLRC5 expression negatively mediates gene expression
      of IFNA and IFNB in the chicken HD11 cell line; therefore, NLRC5 likely has a
      role in positive regulation of IFNA and IFNB expression. No direct relationship
      was found between NLRC5 knockdown and IL-6 and MHC class I expression. Future
      studies will further clarify the roles of NLRC5 and other NLRs in infectious
      diseases of chickens and may increase the efficacy of antiviral vaccine design.

PMID- 22401174
TI  - TRAIL receptor I (DR4) polymorphisms C626G and A683C are associated with an
      increased risk for hepatocellular carcinoma (HCC) in HCV-infected patients.
AB  - BACKGROUND: Tumour surveillance via induction of TRAIL-mediated apoptosis is a
      key mechanism, how the immune system prevents malignancy. To determine if gene
      variants in the TRAIL receptor I (DR4) gene affect the risk of hepatitis C virus
      (HCV)-induced liver cancer (HCC), we analysed DR4 mutations C626G (rs20575) and
      A683C (rs20576) in HCV-infected patients with and without HCC. METHODS:
      Frequencies of DR4 gene polymorphisms were determined by LightSNiP assays in 159
      and 234 HCV-infected patients with HCC and without HCC, respectively. 359 healthy
      controls served as reference population. RESULTS: Distribution of C626G and A683C
      genotypes were not significantly different between healthy controls and HCV
      positive patients without HCC. DR4 variants 626C and 683A occurred at increased
      frequencies in patients with HCC. The risk of HCC was linked to carriage of the
      626C allele and the homozygous 683AA genotype, and the simultaneous presence of
      the two risk variants was confirmed as independent HCC risk factor by Cox
      regression analysis (Odds ratio 1.975, 95% CI 1.205-3.236; p = 0.007).
      Furthermore HCV viral loads were significantly increased in patients who
      simultaneously carried both genetic risk factors (2.69 +/- 0.36 * 10(6) IU/ml vs.
      1.81 +/- 0.23 * 10(6) IU/ml, p = 0.049). CONCLUSIONS: The increased prevalence of
      patients with a 626C allele and the homozygous 683AA genotype in HCV-infected
      patients with HCC suggests that these genetic variants are a risk factor for HCC
      in chronic hepatitis C.

PMID- 22401176
TI  - Gadolinium oxide nanocrystal nonvolatile memory with HfO2/Al2O3 nanostructure
      tunneling layers.
AB  - In this study, Gd2O3 nanocrystal (Gd2O3-NC) memories with nanostructure
      tunneling layers are fabricated to examine their performance. A higher
      programming speed for Gd2O3-NC memories with nanostructure tunneling layers is
      obtained when compared with that of memories using a single tunneling layer. A
      longer data retention (< 15% charge loss after 104 s) is also observed. This is
      due to the increased physical thickness of the nanostructure tunneling layer. The
      activation energy of charge loss at different temperatures is estimated. The
      higher activation energy value (0.13 to 0.17 eV) observed at the initial charge
      loss stage is attributed to the thermionic emission mechanism, while the lower
      one (0.07 to 0.08 eV) observed at the later charge loss stage is attributed to
      the direct tunneling mechanism. Gd2O3-NC memories with nanostructure tunneling
      layers can be operated without degradation over several operation cycles. Such NC
      structures could potentially be used in future nonvolatile memory applications.

PMID- 22401175
TI  - Gene expression analysis of rheumatoid arthritis synovial lining regions by cDNA
      microarray combined with laser microdissection: up-regulation of inflammation
      associated STAT1, IRF1, CXCL9, CXCL10, and CCL5.
AB  - OBJECTIVES: The main histological change in rheumatoid arthritis (RA) is the
      villous proliferation of synovial lining cells, an important source of cytokines
      and chemokines, which are associated with inflammation. The aim of this study was
      to evaluate gene expression in the microdissected synovial lining cells of RA
      patients, using those of osteoarthritis (OA) patients as the control. METHODS:
      Samples were obtained during total joint replacement from 11 RA and five OA
      patients. Total RNA from the synovial lining cells was derived from selected
      specimens by laser microdissection (LMD) for subsequent cDNA microarray analysis.
      In addition, the expression of significant genes was confirmed
      immunohistochemically. RESULTS: The 14 519 genes detected by cDNA microarray were
      used to compare gene expression levels in synovial lining cells from RA with
      those from OA patients. Cluster analysis indicated that RA cells, including low-
      and high-expression subgroups, and OA cells were stored in two main clusters. The
      molecular activity of RA was statistically consistent with its clinical and
      histological activity. Expression levels of signal transducer and activator of
      transcription 1 (STAT1), interferon regulatory factor 1 (IRF1), and the
      chemokines CXCL9, CXCL10, and CCL5 were statistically significantly higher in the
      synovium of RA than in that of OA. Immunohistochemically, the lining synovium of
      RA, but not that of OA, clearly expressed STAT1, IRF1, and chemokines, as was
      seen in microarray analysis combined with LMD. CONCLUSIONS: Our findings indicate
      an important role for lining synovial cells in the inflammatory and proliferative
      processes of RA. Further understanding of the local signalling in structural
      components is important in rheumatology.

PMID- 22401177
TI  - Historical perspective and human consequences of Africanized bee stings in the
      Americas.
AB  - In 1956, Africanized bees began to spread in the American continent from southern
      Brazil, where original African bees mated with European bees. A few years later,
      in 1990, these Africanized bees reached the United States and were found in
      Texas. Currently, these hybrid bees are found in several North American states
      and will probably reach the Canadian border in the future. Although the presence
      of Africanized bees had produced positive effects on Brazilian economy, including
      improvement in crop pollination and in honey production, turning Brazil into a
      major exporter, the negative impacts-such as swarming, aggressive behavior, and
      the ability to mass attack-resulted in serious and fatal envenomation with humans
      and animals. Victims of bee attacks usually develop a severe envenomation
      syndrome characterized by the release of a large amount of cytokines
      [interleukins (IL) IL-1, IL-6, IL-8], and tumor necrosis factor (TNF).
      Subsequently, such cytokines produce an acute inflammatory response that triggers
      adverse effects on skeletal muscles; bone marrow; hepatic and renal functions;
      and cardiovascular, central nervous, and immune systems. Finally, the aim of the
      present review is to study historical characteristics and current status of
      Africanized bees' spread, the composition of their venom, the impact of the bees
      on the Brazilian economy and ecology, and clinical aspects of their stings
      including immune response, and to suggest a protocol for bee sting management
      since there is no safe and effective antivenom available.

PMID- 22401179
TI  - Surface bound states in the continuum.
AB  - We introduce a novel concept of surface bound states in the continuum, i.e.,
      surface modes embedded into the linear spectral band of a discrete lattice. We
      suggest an efficient method for creating such surface modes and the local bounded
      potential necessary to support the embedded modes. We demonstrate that the
      surface embedded modes are structurally stable, and the position of their
      eigenvalues inside the spectral band can be tuned continuously by adding weak
      nonlinearity.

PMID- 22401180
TI  - Procedure for direct measurement of general quantum states using weak
      measurement.
AB  - Recent work by Lundeen et al. [Nature (London) 474, 188 (2011)] directly measured
      the wave function by weakly measuring a variable followed by a normal (i.e.,
      "strong") measurement of the complementary variable. We generalize this method to
      mixed states by considering the weak measurement of various products of these
      observables, thereby providing the density matrix an operational definition in
      terms of a procedure for its direct measurement. The method only requires
      measurements in two bases and can be performed in situ, determining the quantum
      state without destroying it.

PMID- 22401178
TI  - Evaluation of epidemiology and animal data for risk assessment: chlorpyrifos
      developmental neurobehavioral outcomes.
AB  - Developmental neurobehavioral outcomes attributed to exposure to chlorpyrifos
      (CPF) obtained from epidemiologic and animal studies published before June 2010
      were reviewed for risk assessment purposes. For epidemiological studies, this
      review considered (1) overall strength of study design, (2) specificity of CPF
      exposure biomarkers, (3) potential for bias, and (4) Hill guidelines for causal
      inference. In the case of animal studies, this review focused on evaluating the
      consistency of outcomes for developmental neurobehavioral endpoints from in vivo
      mammalian studies that exposed dams and/or offspring to CPF prior to weaning.
      Developmental neuropharmacologic and neuropathologic outcomes were also
      evaluated. Experimental design and methods were examined as part of the weight of
      evidence. There was insufficient evidence that human developmental exposures to
      CPF produce adverse neurobehavioral effects in infants and children across
      different cohort studies that may be relevant to CPF exposure. In animals, few
      behavioral parameters were affected following gestational exposures to 1 mg/kg-d
      but were not consistently reported by different laboratories. For postnatal
      exposures, behavioral effects found in more than one study at 1 mg/kg-d were
      decreased errors on a radial arm maze in female rats and increased errors in
      males dosed subcutaneously from postnatal day (PND) 1 to 4. A similar finding was
      seen in rats exposed orally from PND 1 to 21 with incremental dose levels of 1,
      2, and 4 mg/kg-d, but not in rats dosed with constant dose level of 1 mg/kg-d.
      Neurodevelopmental behavioral, pharmacological, and morphologic effects occurred
      at doses that produced significant brain or red blood cell acetylcholinesterase
      inhibition in dams or offspring.

PMID- 22401181
TI  - Preferred states of decoherence under intermediate system-environment coupling.
AB  - The notion that decoherence rapidly reduces a superposition state to an
      incoherent mixture implicitly adopts a special representation, namely, the
      representation of preferred (pointer) states (PS). For weak or strong system
      envrionment interaction, the behavior of PS is well known. Via a simple dynamical
      model that simulates a two-level system interacting with few other degrees of
      freedom as its environment, it is shown that even for intermediate system
      environment coupling, approximate PS may still emerge from the coherent quantum
      dynamics of the whole system in the absence of any thermal averaging. The found
      PS can also continuously deform to expected limits for weak or strong system
      environment coupling. Computational results are also qualitatively explained. The
      findings should be useful towards further understanding of decoherence and
      quantum thermalization processes.

PMID- 22401182
TI  - Scale invariance and viscosity of a two-dimensional Fermi gas.
AB  - We investigate collective excitations of a harmonically trapped two-dimensional
      Fermi gas from the collisionless (zero sound) to the hydrodynamic (first sound)
      regime. The breathing mode, which is sensitive to the equation of state, is
      observed with an undamped amplitude at a frequency 2 times the dipole mode
      frequency for a large range of interaction strengths and different temperatures.
      This provides evidence for a dynamical SO(2,1) scaling symmetry of the two
      dimensional Fermi gas. Moreover, we investigate the quadrupole mode to measure
      the shear viscosity of the two-dimensional gas and study its temperature
      dependence.

PMID- 22401183
TI  - Aharonov-Casher and scalar Aharonov-Bohm topological effects.
AB  - We reexamine the topological and nonlocal natures of the Aharonov-Casher and
      scalar Aharonov-Bohm phase effects. The underlying U(1) gauge structure is
      exhibited explicitly. And the conditions for developing topological Aharonov
      Casher and scalar Aharonov-Bohm phases are clarified. We analyze the arguments of
      M. Peshkin and H. J. Lipkin [Phys. Rev. Lett. 74, 2847 (1995)] in detail and show
      that they are based on the wrong Hamiltonian which yields their conclusion
      incorrect.

PMID- 22401184
TI  - Almost all quantum states have low entropy rates for any coupling to the
      environment.
AB  - The joint state of a system that is in contact with an environment is called
      lazy, if the entropy rate of the system under any coupling to the environment is
      zero. Necessary and sufficient conditions have recently been established for a
      state to be lazy [Phys. Rev. Lett. 106, 050403 (2011)], and it was shown that
      almost all states of the system and the environment do not have this property
      [Phys. Rev. A 81, 052318 (2010)]. At first glance, this may lead us to believe
      that low entropy rates themselves form an exception, in the sense that most
      states are far from being lazy and have high entropy rates. Here, we show that in
      fact the opposite is true if the environment is sufficiently large. Almost all
      states of the system and the environment are pretty lazy-their entropy rates are
      low for any coupling to the environment.

PMID- 22401185
TI  - Efficient method for computing the maximum-likelihood quantum state from
      measurements with additive Gaussian noise.
AB  - We provide an efficient method for computing the maximum-likelihood mixed quantum
      state (with density matrix rho) given a set of measurement outcomes in a complete
      orthonormal operator basis subject to Gaussian noise. Our method works by first
      changing basis yielding a candidate density matrix MU which may have nonphysical
      (negative) eigenvalues, and then finding the nearest physical state under the 2
      norm. Our algorithm takes at worst O(d(4)) for the basis change plus O(d(3)) for
      finding rho where d is the dimension of the quantum state. In the special case
      where the measurement basis is strings of Pauli operators, the basis change takes
      only O(d(3)) as well. The workhorse of the algorithm is a new linear-time method
      for finding the closest probability distribution (in Euclidean distance) to a set
      of real numbers summing to one.

PMID- 22401186
TI  - Explosive condensation in a mass transport model.
AB  - We study a far-from-equilibrium system of interacting particles, hopping between
      sites of a 1D lattice with a rate which increases with the number of particles at
      interacting sites. We find that clusters of particles, which initially
      spontaneously form in the system, begin to move at increasing speed as they gain
      particles. Ultimately, they produce a moving condensate which comprises a finite
      fraction of the mass in the system. We show that, in contrast with previously
      studied models of condensation, the relaxation time to steady state decreases as
      an inverse power of lnL with system size L and that condensation is instantaneous
      for L->infinity.

PMID- 22401187
TI  - Secure key distribution using correlated randomness in lasers driven by common
      random light.
AB  - We propose a secure key distribution scheme based on correlated physical
      randomness in remote optical scramblers driven by common random light. The
      security of the scheme depends on the practical difficulty of completely
      observing random optical phenomena. We describe a particular realization using
      the synchronization of semiconductor lasers injected with common light of
      randomly varying phase. We experimentally demonstrate the feasibility of the
      scheme over a distance of 120 km.

PMID- 22401188
TI  - Quantum hyperdiffusion in one-dimensional tight-binding lattices.
AB  - Transient quantum hyperdiffusion, namely, faster-than-ballistic wave packet
      spreading for a certain time scale, is found to be a typical feature in tight
      binding lattices if a sublattice with on-site potential is embedded in a uniform
      lattice without on-site potential. The strength of the sublattice on-site
      potential, which can be periodic, disordered, or quasiperiodic, must be below
      certain threshold values for quantum hyperdiffusion to occur. This is explained
      by an energy band mismatch between the sublattice and the rest uniform lattice
      and by the structure of the underlying eigenstates. Cases with a quasiperiodic
      sublattice can yield remarkable hyperdiffusion exponents that are beyond three. A
      phenomenological explanation of hyperdiffusion exponents is also discussed.

PMID- 22401189
TI  - Quantum absorption refrigerator.
AB  - A quantum absorption refrigerator driven by noise is studied with the purpose of
      determining the limitations of cooling to absolute zero. The model consists of a
      working medium coupled simultaneously to hot, cold, and noise baths. Explicit
      expressions for the cooling power are obtained for Gaussian and Poisson white
      noise. The quantum model is consistent with the first and second laws of
      thermodynamics. The third law is quantified; the cooling power J(c) vanishes as
      J(c) ? T(c)(alpha), when T(c)->0, where alpha=d+1 for dissipation by emission and
      absorption of quanta described by a linear coupling to a thermal bosonic field,
      where d is the dimension of the bath.

PMID- 22401190
TI  - Cosmological constant: a lesson from Bose-Einstein condensates.
AB  - The cosmological constant is one of the most pressing problems in modern physics.
      We address this issue from an emergent gravity standpoint, by using an analogue
      gravity model. Indeed, the dynamics of the emergent metric in a Bose-Einstein
      condensate can be described by a Poisson-like equation with a vacuum source term
      reminiscent of a cosmological constant. The direct computation of this term shows
      that in emergent gravity scenarios this constant may be naturally much smaller
      than the naive ground-state energy of the emergent effective field theory. This
      suggests that a proper computation of the cosmological constant would require a
      detailed understanding about how Einstein equations emerge from the full
      microscopic quantum theory. In this light, the cosmological constant appears as a
      decisive test bench for any quantum or emergent gravity scenario.

PMID- 22401191
TI  - Information escaping the correlation hierarchy of the convergence field in the
      study of cosmological parameters.
AB  - Using fits to numerical simulations, we show that the entire hierarchy of moments
      quickly ceases to provide a complete description of the convergence one-point
      probability density function leaving the linear regime. This suggests that the
      full N-point correlation function hierarchy of the convergence field becomes
      quickly generically incomplete and a very poor cosmological probe on nonlinear
      scales. At the scale of unit variance, only 5% of the Fisher information content
      of the one-point probability density function is still contained in its hierarchy
      of moments, making clear that information escaping the hierarchy is a far
      stronger effect than information propagating to higher order moments. It follows
      that the constraints on cosmological parameters achievable through extraction of
      the entire hierarchy become suboptimal by large amounts. A simple logarithmic
      mapping makes the moment hierarchy well suited again for parameter extraction.

PMID- 22401193
TI  - Direct measurement of the formation length of photons.
AB  - We report the first observation of a shoulder in the radiation spectrum from GeV
      electrons in a structured target consisting of two thin and closely spaced foils.
      The position of the shoulder depends on the target spacing and is directly
      connected to the finite formation length of a low-energy photon emitted by an
      ultrarelativistic electron. With the present setup it is possible to control the
      separation of the foils on a MUm scale and hence measure interference effects
      caused by the macroscopic dimensions of the formation length. Several theoretical
      groups have predicted this effect using different methods. Our observations have
      a preference for the modified theory by Blankenbecler but disagree with the
      results of Baier and Katkov.

PMID- 22401194
TI  - Diphoton production at hadron colliders: a fully differential QCD calculation at
      next-to-next-to-leading order.
AB  - We consider direct diphoton production in hadron collisions, and we compute the
      next-to-next-to-leading order QCD radiative corrections at the fully differential
      level. Our calculation uses the q(T) subtraction formalism, and it is implemented
      in a parton-level Monte Carlo program. The program allows the user to apply
      arbitrary kinematical cuts on the final-state photons and the associated jet
      activity and to compute the corresponding distributions in the form of bin
      histograms. We present selected numerical results related to Higgs boson searches
      at the LHC and corresponding results at the Tevatron.

PMID- 22401195
TI  - Top quark production asymmetries A(FB)t and A(FB)l.
AB  - A large forward-backward asymmetry is seen in both the top quark rapidity
      distribution A(FB)(t) and in the rapidity distribution of charged leptons
      A(FB)(l) from top quarks produced at the Tevatron. We study the kinematic and
      dynamic aspects of the relationship of the two observables arising from the spin
      correlation between the charged lepton and the top quark with different
      polarization states. We emphasize the value of both measurements, and we conclude
      that a new physics model which produces more right-handed than left-handed top
      quarks is favored by the present data.

PMID- 22401192
TI  - Search for CP violation in D+/- meson decays to phipi+/-.
AB  - We search for CP violation in Cabibbo-suppressed charged D meson decays by
      measuring the difference between the CP-violating asymmetries for the Cabibbo
      suppressed decays D(+/-)->K(+)K(-)pi(+/-) and the Cabibbo-favored decays D(s)(+/
      )->K(+)K(-)pi(+/-) in the K(+)K(-) mass region of the phi resonance. Using 955 
      fb(-1) of data collected with the Belle detector, we obtain A(CP)(D+
      >phipi+)=(+0.51+/-0.28+/-0.05)%. The measurement improves the sensitivity of
      previous searches by more than a factor of 5. We find no evidence for direct CP
      violation.

PMID- 22401198
TI  - Test of many-electron QED effects in the hyperfine splitting of heavy high-Z
      ions.
AB  - A rigorous evaluation of the two-photon exchange corrections to the hyperfine
      structure in lithiumlike heavy ions is presented. As a result, the theoretical
      accuracy of the specific difference between the hyperfine splitting values of H-
      and Li-like Bi ions is significantly improved. This opens a possibility for the
      stringent test of the many-electron QED effects on a few percent level in the
      strongest electromagnetic field presently available in experiments.

PMID- 22401199
TI  - Experimental demonstration of the Breit interaction which dominates the angular
      distribution of x-ray emission in dielectronic recombination.
AB  - We report the experimentally determined angular distribution of the
      [1s2s(2)2p(1/2)](1)->[1s(2)2s(2)](0) transition in dielectronic recombination of
      Li-like Au. Recently, Fritzsche et al. [Phys. Rev. Lett. 103, 113001 (2009)]
      predicted that the Breit interaction plays a dominant role in the angular
      distribution of this transition. However, the predicted phenomenon has not yet
      been observed experimentally due to technical difficulties in conventional
      methods. To overcome the difficulties, we combine two different measurements with
      an electron beam ion trap (EBIT) to obtain the x-ray angular distribution. One is
      the x-ray measurement at 90 degrees  and another is the integral resonant
      strength measurement through the ion charge abundance in the EBIT. Our
      measurements agree well with the theoretical prediction and confirm the dominance
      of the Breit interaction.

PMID- 22401200
TI  - Attosecond correlated dynamics of two electrons passing through a transition
      state.
AB  - The strong-field induced decay of a doubly excited, transient Coulomb complex
      Ar**->Ar(2+)+2e(-) is explored by tracing correlated two-electron emission in
      nonsequential double ionization of Ar as a function of the carrier-envelope
      phase. Using <6 fs pulses, electron emission is essentially confined to one
      optical cycle. Classical model calculations support that the intermediate Coulomb
      complex has lost memory of its formation dynamics and allows for a consistent,
      though model-dependent definition of "emission time," empowering us to trace
      transition-state two-electron decay dynamics with sub-fs resolution. We find a
      most likely emission time difference of ~200+/-100 as.

PMID- 22401201
TI  - Efimov physics in heteronuclear four-body systems.
AB  - We study three- and four-body Efimov physics in a heteronuclear atomic system
      with three identical heavy bosonic atoms and one light atom. We show that
      exchange of the light atom between the heavy atoms leads to both three- and four
      body features in the low-energy inelastic rate constants that trace to the Efimov
      effect. Further, the effective interaction generated by this exchange can provide
      an additional mechanism for control in ultracold experiments. Finally, we find
      that there is no true four-body Efimov effect-that is, no infinite number of four
      body states in the absence of two- and three-body bound states-resolving a
      decades-long controversy.

PMID- 22401202
TI  - Spatial imaging of the H2(+) vibrational wave function at the quantum limit.
AB  - We experimentally obtained a direct image of the nuclear wave functions of
      H(2)(+) by dissociating the molecule via electron attachment and determining the
      vibrational state using the cold target recoil ion momentum spectroscopy
      technique. Our experiment visualizes the nodal structure of different vibrational
      states. We compare our results to the widely used reflection approximation and to
      quantum simulations and discuss the limits of position measurements in molecules
      imposed by the uncertainty principle.

PMID- 22401203
TI  - Quantum chaos and effective thermalization.
AB  - We demonstrate effective equilibration for unitary quantum dynamics under
      conditions of classical chaos. Focusing on the paradigmatic example of the Dicke
      model, we show how a constructive description of the thermalization process is
      facilitated by the Glauber Q or Husimi function, for which the evolution equation
      turns out to be of Fokker-Planck type. The equation describes a competition of
      classical drift and quantum diffusion in contractive and expansive directions. By
      this mechanism the system follows a "quantum smoothened" approach to equilibrium,
      which avoids the notorious singularities inherent to classical chaotic flows.

PMID- 22401204
TI  - Intense two-cycle laser pulses induce time-dependent bond hardening in a
      polyatomic molecule.
AB  - A time-dependent bond-hardening process is discovered in a polyatomic molecule
      (tetramethyl silane, TMS) using few-cycle pulses of intense 800 nm light. In
      conventional mass spectrometry, symmetrical molecules such as TMS do not exhibit
      a prominent molecular ion (TMS(+)) as unimolecular dissociation into
      [Si(CH(3))(3)](+) proceeds very fast. Under a strong field and few-cycle
      conditions, this dissociation channel is defeated by time-dependent bond
      hardening: a field-induced potential well is created in the TMS(+) potential
      energy curve that effectively traps a wave packet. The time dependence of this
      bond-hardening process is verified using longer-duration (>=100 fs) pulses; the
      relatively slower falloff of optical field in such pulses allows the initially
      trapped wave packet to leak out, thereby rendering TMS(+) unstable once again.

PMID- 22401205
TI  - Atom-scale ptychographic electron diffractive imaging of boron nitride cones.
AB  - Ptychographic coherent diffractive imaging (CDI) has been extensively applied
      using both x rays and electrons. The extension to atomic resolution has been
      elusive. This Letter demonstrates ptychographic electron diffractive imaging at
      atomic resolution, permitting identification of structure in a boron nitride
      helical cone at a resolution of order 1 A, beyond that of comparative Z-contrast
      images. A scanning transmission electron microscope is used to create a diverging
      illumination in a defocused Fresnel CDI geometry, providing a robust strategy
      leading to a unique solution.

PMID- 22401196
TI  - Strangeness enhancement in Cu-Cu and Au-Au collisions at ?S(NN)=200 GeV.
AB  - We report new STAR measurements of midrapidity yields for the Lambda, Lambda[over
      -], K(S)(0), Xi(-), Xi[over -](+), Omega(-), Omega[over -](+) particles in Cu+Cu
      collisions at ?S(NN)==200  GeV, and midrapidity yields for the Lambda,
      Lambda[over -], K(S)(0) particles in Au+Au at ?S(NN)==200  GeV. We show that, at
      a given number of participating nucleons, the production of strange hadrons is
      higher in Cu+Cu collisions than in Au+Au collisions at the same center-of-mass
      energy. We find that aspects of the enhancement factors for all particles can be
      described by a parametrization based on the fraction of participants that undergo
      multiple collisions.

PMID- 22401197
TI  - Identified hadron compositions in p+p and Au+Au collisions at high transverse
      momenta at ?S(NN)=200 GeV.
AB  - We report transverse momentum (p(T)<=15  GeV/c) spectra of pi(+/-), K(+/-), p,
      p[over -], K(S)(0), and rho(0) at midrapidity in p+p and Au+Au collisions at
      ?S(NN)=200  GeV. Perturbative QCD calculations are consistent with pi(+/-)
      spectra in p+p collisions but do not reproduce K and p(p[over -]) spectra. The
      observed decreasing antiparticle-to-particle ratios with increasing p(T) provide
      experimental evidence for varying quark and gluon jet contributions to high-p(T)
      hadron yields. The relative hadron abundances in Au+Au at p(T)?8  GeV/c are
      measured to be similar to the p+p results, despite the expected Casimir effect
      for parton energy loss.

PMID- 22401206
TI  - Stress defocusing in anisotropic compaction of thin sheets.
AB  - We address the crumpling of thin sheets in between large scale curved cylinders.
      In contrast with the usual crushing of a paper ball, one curvature of the sheet
      is fixed here by the cylinders radius, yielding an anisotropic compaction. As
      compaction proceeds, it is found that sheets first develop singular folds
      involving ridges or developable cones, but eventually turn to regular folds free
      of any geometrical singularities, without ever having entered the plastic regime.
      This surprising uncrumpling transition corresponds to a stress defocusing. It is
      understood from a balance between bending and stretching energies on regular
      states.

PMID- 22401207
TI  - Turbulence in noninteger dimensions by fractal Fourier decimation.
AB  - Fractal decimation reduces the effective dimensionality D of a flow by keeping
      only a (randomly chosen) set of Fourier modes whose number in a ball of radius k
      is proportional to k(D) for large k. At the critical dimension D(c)=4/3 there is
      an equilibrium Gibbs state with a k(-5/3) spectrum, as in V. L'vov et al., Phys.
      Rev. Lett. 89, 064501 (2002). Spectral simulations of fractally decimated two
      dimensional turbulence show that the inverse cascade persists below D=2 with a
      rapidly rising Kolmogorov constant, likely to diverge as (D-4/3)(-2/3).

PMID- 22401208
TI  - Suppression of complex fingerlike patterns at the interface between air and a
      viscous fluid by elastic membranes.
AB  - Growth of complex dendritic fingers at the interface of air and a viscous fluid
      in the narrow gap between two parallel plates is an archetypical problem of
      pattern formation. We find a surprisingly effective means of suppressing this
      instability by replacing one of the plates with an elastic membrane. The
      resulting fluid-structure interaction fundamentally alters the interfacial
      patterns that develop and considerably delays the onset of fingering. We analyze
      the dependence of the instability on the parameters of the system and present
      scaling arguments to explain the experimentally observed behavior.

PMID- 22401209
TI  - Skating on a film of air: drops impacting on a surface.
AB  - The commonly accepted description of drops impacting on a surface typically
      ignores the essential role of the air that is trapped between the impacting drop
      and the surface. Here we describe a new imaging modality that is sensitive to the
      behavior right at the surface. We show that a very thin film of air, only a few
      tens of nanometers thick, remains trapped between the falling drop and the
      surface as the drop spreads. The thin film of air serves to lubricate the drop
      enabling the fluid to skate on the air film laterally outward at surprisingly
      high velocities, consistent with theoretical predictions. Eventually this thin
      film of air breaks down as the fluid wets the surface via a spinodal-like
      mechanism. Our results show that the dynamics of impacting drops are much more
      complex than previously thought, with a rich array of unexpected phenomena that
      require rethinking classic paradigms.

PMID- 22401210
TI  - Three-wave interactions and spatiotemporal chaos.
AB  - Three-wave interactions form the basis of our understanding of many pattern
      forming systems because they encapsulate the most basic nonlinear interactions.
      In problems with two comparable length scales, it is possible for two waves of
      the shorter wavelength to interact with one wave of the longer, as well as for
      two waves of the longer wavelength to interact with one wave of the shorter.
      Consideration of both types of three-wave interactions can generically explain
      the presence of complex patterns and spatiotemporal chaos. Two length scales
      arise naturally in the Faraday wave experiment, and our results enable some
      previously unexplained experimental observations of spatiotemporal chaos to be
      interpreted in a new light. Our predictions are illustrated with numerical
      simulations of a model partial differential equation.

PMID- 22401211
TI  - Dynamics of collapse of air films in drop impact.
AB  - Liquid drops hitting solid surfaces deform substantially under the influence of
      the ambient air that needs to be squeezed out before the liquid actually touches
      the solid. Nanometer- and microsecond-resolved dual wavelength interferometry
      reveals a complex evolution of the interface between the drop and the gas layer
      underneath. For intermediate impact speeds (We~1...10) the layer thickness can
      develop one or two local minima-reproduced in numerical calculations-that
      eventually lead to the nucleation of solid-liquid contact at a We-dependent
      radial position, from a film thickness >200  nm. Solid-liquid contact spreads at
      a speed involving capillarity, liquid viscosity and inertia.

PMID- 22401212
TI  - Breakup of liquid filaments.
AB  - Whether a thin filament of liquid separates into two or more droplets or
      eventually condenses lengthwise to form a single larger drop depends on the
      liquid's density, viscosity, and surface tension and on the initial dimensions of
      the filament. Surface tension drives two competing processes, pinching-off and
      shortening, and the relative time scales of these, controlled by the balance
      between capillary and viscous forces, determine the final outcome. Here we
      provide experimental evidence for the conditions under which a liquid filament
      will break up into drops, in terms of a wide range of two dimensionless
      quantities: the aspect ratio of the filament and the Ohnesorge number. Filaments
      which do not break up into multiple droplets demand a high liquid viscosity or a
      small aspect ratio.

PMID- 22401213
TI  - Higher order spin resonances in a 2.1-GeV/c polarized proton beam.
AB  - Spin resonances can depolarize or spin flip a polarized beam. We studied 1st and
      higher order spin resonances with stored 2.1  GeV/c vertically polarized protons.
      The 1st order vertical (nu(y)) resonance caused almost full spin flip, while some
      higher order nu(y) resonances caused partial depolarization. The 1st order
      horizontal (nu(x)) resonance caused almost full depolarization, while some higher
      order nu(x) resonances again caused partial depolarization. Moreover, a 2nd order
      nu(x) resonance is about as strong as some 3rd order nu(x) resonances, while some
      3rd order nu(y) resonances are much stronger than a 2nd order nu(y) resonance.
      One thought that nu(y) spin resonances are far stronger than nu(x), and that
      lower order resonances are stronger than higher order; the data do not support
      this.

PMID- 22401214
TI  - Quantized orbital angular momentum transfer and magnetic dichroism in the
      interaction of electron vortices with matter.
AB  - Following the very recent experimental realization of electron vortices, we
      consider their interaction with matter, in particular, the transfer of orbital
      angular momentum in the context of electron energy-loss spectroscopy, and the
      recently observed dichroism in thin film magnetized iron samples. We show here
      that orbital angular momentum exchange does indeed occur between electron
      vortices and the internal electronic-type motion, as well as center-of-mass
      motion of atoms in the electric dipole approximation. This contrasts with the
      case of optical vortices where such transfer only occurs in transitions involving
      multipoles higher than the dipole. The physical basis of the observed dichroism
      is explained.

PMID- 22401216
TI  - Evidence for stratification of deuterium-tritium fuel in inertial confinement
      fusion implosions.
AB  - Measurements of the D(d,p)T (dd) and T(t,2n)(4)He (tt) reaction yields have been
      compared with those of the D(t,n)(4)He (dt) reaction yield, using deuterium
      tritium gas-filled inertial confinement fusion capsule implosions. In these
      experiments, carried out on the OMEGA laser, absolute spectral measurements of dd
      protons and tt neutrons were obtained. From these measurements, it was concluded
      that the dd yield is anomalously low and the tt yield is anomalously high
      relative to the dt yield, an observation that we conjecture to be caused by a
      stratification of the fuel in the implosion core. This effect may be present in
      ignition experiments planned on the National Ignition Facility.

PMID- 22401215
TI  - Deducing the electron-beam diameter in a laser-plasma accelerator using x-ray
      betatron radiation.
AB  - We investigate the properties of a laser-plasma electron accelerator as a bright
      source of keV x-ray radiation. During the interaction, the electrons undergo
      betatron oscillations and from the carefully measured x-ray spectrum the
      oscillation amplitude of the electrons can be deduced which decreases with
      increasing electron energies. From the oscillation amplitude and the
      independently measured x-ray source size of (1.8+/-0.3) MUm we are able to
      estimate the electron bunch diameter to be (1.6+/-0.3) MUm.

PMID- 22401217
TI  - Experimental identification of electromagnetically induced transparency in
      magnetized plasma.
AB  - We report the first experimental identification of the new wave branch at
      electron cyclotron frequency produced by the injection of a frequency-matched
      intense pump wave in magnetized plasma [A. G. Litvak and M. D. Tokman, Phys. Rev.
      Lett. 88, 095003 (2002); G. Shvets and J. S. Wurtele, Phys. Rev. Lett. 89, 115003
      (2002)], which is a classical phenomenon analogous to electromagnetically induced
      transparency (EIT) in quantum systems. By using a frequency-sweep interferometer,
      we directly detected the dispersion relation of the plasma EIT branch for
      propagation parallel to the background magnetic field. The bandwidth of the EIT
      window was correlated with the pump-wave electric field and was found to agree
      with the theoretical prediction.

PMID- 22401218
TI  - Brunel-dominated proton acceleration with a few-cycle laser pulse.
AB  - Experimental measurements of backward accelerated protons are presented. The beam
      is produced when an ultrashort (5 fs) laser pulse, delivered by a kHz laser
      system, with a high temporal contrast (10(8)), interacts with a thick solid
      target. Under these conditions, proton cutoff energy dependence with laser
      parameters, such as pulse energy, polarization (from p to s), and pulse duration
      (from 5 to 500 fs), is studied. Theoretical model and two-dimensional particle-in
      cell simulations, in good agreement with a large set of experimental results,
      indicate that proton acceleration is directly driven by Brunel electrons, in
      contrast to conventional target normal sheath acceleration that relies on
      electron thermal pressure.

PMID- 22401219
TI  - Spin caloritronics in noncondensed Bose gases.
AB  - We consider coupled spin and heat transport in a two-component atomic Bose gas in
      the noncondensed state. We find that the transport coefficients show a
      temperature dependence reflecting the bosonic enhancement of scattering and
      discuss experimental signatures of the spin-heat coupling in spin accumulation,
      spin separation, and total dissipation. Close to the critical temperature for
      Bose-Einstein condensation, we find that the spin-heat coupling is strongly
      reduced, which is also reflected in the spin caloritronics figure of merit that
      determines the thermodynamic efficiency of spin-heat conversion.

PMID- 22401220
TI  - Topologically induced avoided band crossing in an optical checkerboard lattice.
AB  - We report on the condensation of bosons in the 4th band of an optical
      checkerboard lattice providing a topologically induced avoided band crossing
      involving the 2nd, 3rd, and 4th Bloch bands. When the condensate is slowly tuned
      through the avoided crossing, accelerated band relaxation arises and the zero
      momentum approximately C4-invariant condensate wave function acquires finite
      momentum order and reduced C2 symmetry. For faster tuning Landau-Zener
      oscillations between different superfluid orders arise, which are used to
      characterize the avoided crossing.

PMID- 22401221
TI  - Fermionization of two distinguishable fermions.
AB  - We study a system of two distinguishable fermions in a 1D harmonic potential.
      This system has the exceptional property that there is an analytic solution for
      arbitrary values of the interparticle interaction. We tune the interaction
      strength and compare the measured properties of the system to the theoretical
      prediction. For diverging interaction strength, the energy and square modulus of
      the wave function for two distinguishable particles are the same as for a system
      of two noninteracting identical fermions. This is referred to as fermionization.
      We have observed this phenomenon by directly comparing two distinguishable
      fermions with diverging interaction strength with two identical fermions in the
      same potential. We observe good agreement between experiment and theory. By
      adding more particles our system can be used as a quantum simulator for more
      complex systems where no theoretical solution is available.

PMID- 22401222
TI  - Condensates of p-wave pairs are exact solutions for rotating two-component Bose
      gases.
AB  - We derive exact analytical results for the wave functions and energies of
      harmonically trapped two-component Bose-Einstein condensates with weakly
      repulsive interactions under rotation. The isospin symmetric wave functions are
      universal and do not depend on the matrix elements of the two-body interaction.
      The comparison with the results from numerical diagonalization shows that the
      ground state and low-lying excitations consist of condensates of p-wave pairs for
      repulsive contact interactions, Coulomb interactions, and the repulsive
      interactions between aligned dipoles.

PMID- 22401223
TI  - Core-level spectroscopy of point defects in single layer h-BN.
AB  - Electron energy-loss spectroscopy (EELS) is used to analyze single-layered
      hexagonal boron-nitride with or without point defects. EELS profiles using a 0.1
      nm probe clearly discriminate the chemical species of single atoms but show
      different delocalization of the boron and nitrogen K edges. A monovacancy at the
      boron site is unambiguously identified and the electronic state of its nearest
      neighboring nitrogen atoms is examined by energy-loss near edge fine structure
      analysis, which demonstrates a prominent defect state. Theoretical calculations
      suggest that the observed prepeak originates from the 1s to lowest unoccupied
      molecular orbital excitation of dangling nitrogen bonds, which is substantially
      lowered in energy with respect to the three coordinated nitrogen atoms.

PMID- 22401224
TI  - Direct insight into grain boundary reconstruction in polycrystalline Cu(In,Ga)SE2
      with atomic resolution.
AB  - This work presents results from high-resolution scanning transmission electron
      microscopy and electron energy-loss spectroscopy on twin boundaries (TBs) and
      nontwin grain boundaries (GBs) in Cu(In,Ga)Se(2) thin films. It is shown that the
      atomic reconstruction is different for different symmetries of the grain
      boundaries. We are able to confirm the model proposed by Persson and Zunger
      [Phys. Rev. Lett. 91, 266401 (2003)] for Se-Se-terminated Sigma3 {112} TBs,
      showing Cu depletion and In enrichment in the two atomic planes closest to the
      TB. On the contrary, Cu depletion without In enrichment is detected for a cation
      Se-terminated TB. At nontwin GBs, always a strong anticorrelation of Cu and In
      signals is detected suggesting that the formation of In(Cu) or Cu(In) antisites
      within a very confined region of smaller than 1 nm is an essential element in the
      reconstruction of these GBs.

PMID- 22401225
TI  - Nonequilibrium route to nanodiamond with astrophysical implications.
AB  - Nanometer-sized diamond grains are commonly found in primitive chondritic
      meteorites, but their origin is puzzling. Using evidence from atomistic
      simulation, we establish a mechanism by which nanodiamonds form abundantly in
      space in a two-stage process involving condensation of vapor to form carbon
      onions followed by transformation to nanodiamond in an energetic impact. This
      nonequilibrium process is consistent with common environments in space and
      invokes the fewest assumptions of any proposed model. Accordingly, our model can
      explain nanodiamond formation in both presolar and solar environments. The model
      provides an attractive framework for understanding noble gas incorporation and
      explains all key features of meteoritic nanodiamond, including size, shape, and
      polytype. By understanding the creation of nanodiamonds, new opportunities arise
      for their exploitation as a powerful astrophysical probe.

PMID- 22401226
TI  - Universality of the plastic instability in strained amorphous solids.
AB  - By comparing the response to external strains in metallic glasses and in Lennard
      Jones glasses we find a quantitative universality of the fundamental plastic
      instabilities in the athermal, quasistatic limit. Microscopically these two types
      of glasses are as different as one can imagine, the latter being determined by
      binary interactions, whereas the former is determined by multiple interactions
      due to the effect of the electron gas that cannot be disregarded. In spite of
      this enormous difference the plastic instability is the same saddle-node
      bifurcation. As a result, the statistics of stress and energy drops in the
      elastoplastic steady state are universal, sharing the same system-size exponents.

PMID- 22401227
TI  - Thermal conductance of ballistic point contacts.
AB  - We study the thermal conductance of ballistic point contacts. These contacts are
      realized as few nanometer long pillars in so-called air-gap heterostructures
      (AGHs). The pillar length is orders of magnitude smaller than the mean free path
      of the phonons up to room temperature. Because of the small dimension and the low
      density of the pillars, the thermal conductance of the AGHs is several orders of
      magnitude reduced in comparison to bulk structures. The measurement results are
      in quantitative agreement with a simple model that is based on the Boltzmann
      transport equation.

PMID- 22401228
TI  - Structures, energetics, and dynamics of helium adsorbed on isolated fullerene
      ions.
AB  - Helium adsorbed on C(60)(+) and C(70)(+) exhibits phenomena akin to helium on
      graphite. Mass spectra suggest that commensurate layers form when all carbon
      hexagons and pentagons are occupied by one He each, but that the solvation shell
      does not close until 60 He atoms are adsorbed on C(60)(+), or 62 on C(70)(+).
      Molecular dynamics simulations of C(60)He(n)(+) at 4 K show that the commensurate
      phase is solid. Helium added to C(60)He(32)(+) will displace some atoms from
      pentagonal sites, leading to coexistence of a registered layer of immobile atoms
      interlaced with a nonregistered layer of mobile atoms.

PMID- 22401229
TI  - Shape transitions in strained Cu islands on Ni(100): kinetics versus energetics.
AB  - We examine the ramified islands observed in submonolayer Cu/Ni(100) growth. Our
      results indicate that the strain-energy contribution to the dependence of island
      energy on shape is surprisingly weak. In contrast, our accelerated dynamics
      simulations indicate that unexpected concerted popout processes occurring at step
      edges may be responsible. Kinetic Monte Carlo (KMC) simulations which include
      these processes produce island shapes which are very similar to those observed in
      experiment. These results suggest that the shape transition is of kinetic origin
      but is strongly mediated by strain.

PMID- 22401230
TI  - Mott transition in the two-dimensional Hubbard model.
AB  - Spectral properties of the two-dimensional Hubbard model near the Mott transition
      are investigated by using cluster perturbation theory. The Mott transition is
      characterized by freezing of the charge degrees of freedom in a single-particle
      excitation that leads continuously to the magnetic excitation of the Mott
      insulator. Various anomalous spectral features observed in cuprate high
      temperature superconductors are explained in a unified manner as properties near
      the Mott transition.

PMID- 22401231
TI  - Quantum Hall effect, screening, and layer-polarized insulating states in twisted
      bilayer graphene.
AB  - We investigate electronic transport in dual-gated twisted-bilayer graphene.
      Despite the subnanometer proximity between the layers, we identify independent
      contributions to the magnetoresistance from the graphene Landau level spectrum of
      each layer. We demonstrate that the filling factor of each layer can be
      independently controlled via the dual gates, which we use to induce Landau level
      crossings between the layers. By analyzing the gate dependence of the Landau
      level crossings, we characterize the finite interlayer screening and extract the
      capacitance between the atomically spaced layers. At zero filling factor, we
      observe an insulating state at large displacement fields, which can be explained
      by the presence of counterpropagating edge states with interlayer coupling.

PMID- 22401232
TI  - Spontaneously gapped ground state in suspended bilayer graphene.
AB  - Bilayer graphene bears an eightfold degeneracy due to spin, valley, and layer
      symmetry, allowing for a wealth of broken symmetry states induced by magnetic or
      electric fields, by strain, or even spontaneously by interaction. We study the
      electrical transport in clean current annealed suspended bilayer graphene. We
      find two kinds of devices. In bilayers of type B1 the eightfold zero-energy
      Landau level is partially lifted above a threshold field revealing an insulating
      nu=0 quantum-Hall state at the charge neutrality point. In bilayers of type B2
      the Landau level lifting is full and a gap appears in the differential
      conductance even at zero magnetic field, suggesting an insulating spontaneously
      broken symmetry state. Unlike B1, the minimum conductance in B2 is not
      exponentially suppressed, but remains finite with a value G is < or approximately
      equall to e(2)/h even in a large magnetic field. We suggest that this phase of B2
      is insulating in the bulk and bound by compressible edge states.

PMID- 22401233
TI  - Microscopic evidence for the modification of the electronic structure at grain
      boundaries of Cu(In(1-x),Ga(x))Se2 films.
AB  - We investigated the electronic properties around grain boundaries of
      polycrystalline Cu(In(1-x),Ga(x)Se(2)) films as a function of Ga content, using
      scanning tunneling spectroscopy. Spectra acquired on samples with low Ga content
      (x=0 and 0.33) reveal downward band bending with respect to adjacent p-type
      grains, suggesting type inversion at the surface of grain boundaries. Such a
      behavior was not observed for samples with high Ga contents. These results are
      consistent with our atomic force microscopy data and may shed light on the origin
      of the x-dependent efficiency for polycrystalline Cu(In(1-x),Ga(x)Se(2))-based
      solar cells.

PMID- 22401234
TI  - Spin drift velocity, polarization, and current-driven domain-wall motion in
      (Ga,Mn)(As,P).
AB  - Current-driven domain-wall motion is studied in (Ga,Mn)(As,P) ferromagnetic
      semiconducting tracks with perpendicular anisotropy. A linear steady state flow
      regime is observed over a large temperature range of the ferromagnetic phase
      (0.1T(c)<T<T(c)). Close to 0 K, the domain-wall velocity is found to coincide
      with the spin drift velocity. This result is obtained below the intrinsic
      threshold for domain-wall motion which implies a nonadiabatic contribution to the
      spin transfer torque. The current spin polarization is deduced close to 0 K and
      to T(c). It suggests that the temperature dependence of the spin polarization can
      be inferred from the domain-wall dynamics.

PMID- 22401235
TI  - Spectroscopy of single donors at ZnO(0001) surfaces.
AB  - Donors near the polar (0001) surface of nominally undoped ZnO were investigated
      with scanning tunneling microscopy at 5 K. Spatially resolved spectroscopy
      reveals single and double charging. Equidistant peaks in spectra of ionized
      donors are attributed to polaron excitation. The data are consistent with doping
      due to Zn interstitials or complexes.

PMID- 22401236
TI  - Transport inefficiency in branched-out mesoscopic networks: an analog of the
      Braess paradox.
AB  - We present evidence for a counterintuitive behavior of semiconductor mesoscopic
      networks that is the analog of the Braess paradox encountered in classical
      networks. A numerical simulation of quantum transport in a two-branch mesoscopic
      network reveals that adding a third branch can paradoxically induce transport
      inefficiency that manifests itself in a sizable conductance drop of the network.
      A scanning-probe experiment using a biased tip to modulate the transmission of
      one branch in the network reveals the occurrence of this paradox by mapping the
      conductance variation as a function of the tip voltage and position.

PMID- 22401237
TI  - Scattering phase of quantum dots: emergence of universal behavior.
AB  - We investigate scattering through chaotic ballistic quantum dots in the Coulomb
      blockade regime. Focusing on the scattering phase, we show that large universal
      sequences emerge in the short wavelength limit, where phase lapses of pi
      systematically occur between two consecutive resonances. Our results are
      corroborated by numerics and are in qualitative agreement with existing
      experiments.

PMID- 22401238
TI  - Quantum transport and two-parameter scaling at the surface of a weak topological
      insulator.
AB  - Weak topological insulators have an even number of Dirac cones in their surface
      spectrum and are thought to be unstable to disorder, which leads to an insulating
      surface. Here we argue that the presence of disorder alone will not localize the
      surface states; rather, the presence of a time-reversal symmetric mass term is
      required for localization. Through numerical simulations, we show that in the
      absence of the mass term the surface always flow to a stable metallic phase and
      the conductivity obeys a one-parameter scaling relation, just as in the case of a
      strong topological insulator surface. With the inclusion of the mass, the
      transport properties of the surface of a weak topological insulator follow a two
      parameter scaling form.

PMID- 22401239
TI  - Polarons in suspended carbon nanotubes.
AB  - We prove theoretically the possibility of electric-field controlled polaron
      formation involving flexural (bending) modes in suspended carbon nanotubes. Upon
      increasing the field, the ground state of the system with a single extra electron
      undergoes a first-order phase transition between an extended state and a
      localized polaron state. For a common experimental setup, the threshold electric
      field is only of the order of approximately equal 5*10(-2) V/MUm.

PMID- 22401240
TI  - Lateral quantization of two-dimensional electron states by embedded Ag
      nanocrystals.
AB  - We show that quantization of image-potential state (IS) electrons above the
      surface of nanostructures can be experimentally achieved by Ag nanocrystals that
      appear as stacking-fault tetrahedrons (SFTs) at Ag(111) surfaces. By means of
      cryogenic scanning tunneling spectroscopy, the n=1 IS of the Ag(111) surface is
      revealed to split up in discrete energy levels, which is accompanied by the
      formation of pronounced standing wave patterns that directly reflect the
      eigenstates of the SFT surface. The IS confinement behavior is compared to that
      of the surface state electrons in the SFT surface and can be directly linked to
      the particle-in-a-box model. ISs provide a novel playground for investigating
      quantum size effects and defect-induced scattering above nanostructured surfaces.

PMID- 22401241
TI  - First-order reorientation transition of the flux-line lattice in CaAlSi.
AB  - The flux-line lattice in CaAlSi has been studied by small-angle neutron
      scattering. A well-defined hexagonal flux-line lattice is seen just above H(c1)
      in an applied field of only 54 Oe. A 30 degrees  reorientation of this vortex
      lattice has been observed in a very low field of 200 Oe. This reorientation
      transition appears to be first-order and could be explained by nonlocal effects.
      The magnetic field dependence of the form factor is well-described by a single
      penetration depth of lambda=1496(1) A and a single coherence length of xi=307(1)
      A at 2 K. At 1.5 K, the penetration depth anisotropy is gamma(lambda)=2.7(1),
      with the field applied perpendicular to the c axis, and agrees with the coherence
      length anisotropy determined from critical field measurements.

PMID- 22401242
TI  - Specular Andreev reflection in the interface of a two-dimensional semiconductor
      with Rashba spin-orbit coupling and a d-wave superconductor.
AB  - We reveal that the recently discovered specular Andreev reflection (SAR) [C. W.
      J. Beenakker, Phys. Rev. Lett. 97, 067007 (2006)] can occur in semiconductors
      where the spin-orbit coupling is finite. We demonstrate this finding in the
      hybrid of a two-dimensional electron gas with Rashba spin-orbit coupling and a
      superconductor. In the limit of low density or a strong spin-orbit coupling,
      specular Andreev reflection is finite. We also show that unit electron-hole
      conversion is possible in a specular Andreev reflection due to the different
      topological structures of the equal-energy surface between electrons and holes.
      The SAR in the semiconductor is determined by the relative orientation of wave
      vector to group velocity, which can be analyzed by ray equations.

PMID- 22401243
TI  - Textured superconducting phase in the heavy fermion CeRhIn5.
AB  - When antiferromagnetism and unconventional superconductivity coexist in CeRhIn(5)
      there is a significant temperature difference between resistively and
      thermodynamically determined transitions into the superconducting state. In this
      state, anisotropic transport near the superconducting transition reveals the
      emergence of textured superconducting planes that appear without a change in
      translational symmetry of the lattice. CeRhIn(5) is not unique in exhibiting
      these behaviors, indicating that textured superconductivity may be a general
      consequence of coexisting orders in correlated electron materials.

PMID- 22401244
TI  - Intrinsic optical dichroism in the chiral superconducting state of Sr2RuO4.
AB  - We present an analysis of the Hall conductivity sigma(xy)(omega,T) in time
      reversal symmetry breaking states of exotic superconductors. We find that the
      dichroic signal is nonzero in systems with interband order parameters. This new
      intrinsic mechanism may explain the Kerr effect observed in strontium ruthenate
      and possibly other superconductors. We predict coherence factor effects in the
      temperature dependence of the imaginary part of the ac Hall conductivity
      Imsigma(xy)(omega,T), which can be tested experimentally.

PMID- 22401245
TI  - Disentangling the physical contributions to the electrical resistance in magnetic
      domain walls: a multiscale study.
AB  - We analyze the origin of the electrical resistance arising in domain walls of
      perpendicularly magnetized materials by considering a superposition of
      anisotropic magnetoresistance and the resistance implied by the magnetization
      chirality. The domain wall profiles of L1(0)-FePd and L1(0)-FePt are determined
      by micromagnetic simulations based on which we perform first-principles
      calculations to quantify electron transport through the core and closure region
      of the walls. The wall resistance, being twice as high in L1(0)-FePd than in
      L1(0)-FePt, is found to be clearly dominated in both cases by a high gradient of
      magnetization rotation, which agrees well with experimental observations.

PMID- 22401246
TI  - Spin wave measurements over the full Brillouin zone of multiferroic BiFeO3.
AB  - Using the inelastic neutron scattering technique, we measured the spin wave
      dispersion over the entire Brillouin zone of room temperature multiferroic
      BiFeO(3) single crystals with magnetic excitations extending to as high as 72.5
      meV. The full spin waves can be explained by a simple Heisenberg Hamiltonian with
      a nearest-neighbor exchange interaction (J=4.38 meV), a next-nearest-neighbor
      exchange interaction (J'=0.15 meV), and a Dzyaloshinskii-Moriya-like term
      (D=0.107 meV). This simple Hamiltonian determined, for the first time, for
      BiFeO(3) provides a fundamental ingredient for understanding the novel magnetic
      properties of BiFeO(3).

PMID- 22401247
TI  - Conduction of topologically protected charged ferroelectric domain walls.
AB  - We report on the observation of nanoscale conduction at ferroelectric domain
      walls in hexagonal HoMnO(3) protected by the topology of multiferroic vortices
      using in situ conductive atomic force microscopy, piezoresponse force microscopy,
      and Kelvin-probe force microscopy at low temperatures. In addition to previously
      observed Schottky-like rectification at low bias [Phys. Rev. Lett. 104, 217601
      (2010)], conductance spectra reveal that negatively charged tail-to-tail walls
      exhibit enhanced conduction at high forward bias, while positively charged head
      to-head walls exhibit suppressed conduction at high reverse bias. Our results
      pave the way for understanding the semiconducting properties of the domains and
      domain walls in small-gap ferroelectrics.

PMID- 22401248
TI  - Coupling of magnetic and ferroelectric hysteresis by a multicomponent magnetic
      structure in Mn2GeO4.
AB  - The olivine compound Mn(2)GeO(4) is shown to feature both a ferroelectric
      polarization and a ferromagnetic magnetization that are directly coupled and
      point along the same direction. We show that a spin spiral generates
      ferroelectricity, and a canted commensurate order leads to weak ferromagnetism.
      Symmetry suggests that the direct coupling between the ferromagnetism and
      ferroelectricity is mediated by Dzyaloshinskii-Moriya interactions that exist
      only in the ferroelectric phase, controlling both the sense of the spiral
      rotation and the canting of the commensurate structure. Our study demonstrates
      how multicomponent magnetic structures found in magnetically frustrated materials
      like Mn(2)GeO(4) provide a new route towards functional materials that exhibit
      coupled ferromagnetism and ferroelectricity.

PMID- 22401249
TI  - Size dependence of exchange bias in Co/CoO nanostructures.
AB  - In Co/CoO nanostructures, of dimensions l*3l, at small Co thickness (~6,10 nm), a
      strong increase in the bias field and the associated coercive field are found as
      the nanostructure size is reduced from l=120 nm to l=30 nm. This property
      indicates that the characteristic length D(AF) within the antiferromagnet which
      governs exchange-bias effects is the nanostructure size. By contrast, at larger
      Co thickness (~23 nm), the exchange-bias field does not depend on the
      nanostructure size, implying that D(AF) is smaller than the nanostructure size.
      The results are discussed in the framework of the Malozemoff model, taking into
      account that the coupling between CoO grains is weak. Exchange bias is dominated
      either by coupling within the antiferromagnetic layer (6- and 10-nm-thick Co
      samples) or by ferromagnetic-antiferromagnetic interfacial coupling (23-nm-thick
      Co sample).

PMID- 22401250
TI  - Observation of complex bound states in the spin-1/2 Heisenberg XXZ chain using
      local quantum quenches.
AB  - We consider the nonequilibrium evolution in the spin-1/2 XXZ Heisenberg chain for
      fixed magnetization after a local quantum quench. This model is equivalent to
      interacting spinless fermions. Initially an infinite magnetic field is applied to
      n consecutive sites and the ground state is calculated. At time t=0 the field is
      switched off and the time evolution of observables such as the z component of
      spin is computed using the time evolving block decimation algorithm. We find that
      the observables exhibit strong signatures of linearly propagating spinon and
      bound state excitations. These persist even when integrability-breaking
      perturbations are included. Since bound states ("strings") are notoriously
      difficult to observe using conventional probes such as inelastic neutron
      scattering, we conclude that local quantum quenches are an ideal setting for
      studying their properties. We comment on implications of our results for cold
      atom experiments.

PMID- 22401251
TI  - Magnetic nonuniformity and thermal hysteresis of magnetism in a manganite thin
      film.
AB  - We measured the chemical and magnetic depth profiles of a single crystalline
      (La(1-x)Pr(x))(1-y)Ca(y)MnO(3-delta) (x=0.52+/-0.05, y=0.23+/-0.04, delta=0.14+/
      0.10) film grown on a NdGaO(3) substrate using x-ray reflectometry, electron
      microscopy, electron energy-loss spectroscopy, and polarized neutron
      reflectometry. Our data indicate that the film exhibits coexistence of different
      magnetic phases as a function of depth. The magnetic depth profile is correlated
      with a variation of chemical composition with depth. The thermal hysteresis of
      ferromagnetic order in the film suggests a first-order ferromagnetic transition
      at low temperatures.

PMID- 22401252
TI  - Dimensionality selection in a molecule-based magnet.
AB  - Gaining control of the building blocks of magnetic materials and thereby
      achieving particular characteristics will make possible the design and growth of
      bespoke magnetic devices. While progress in the synthesis of molecular materials,
      and especially coordination polymers, represents a significant step towards this
      goal, the ability to tune the magnetic interactions within a particular framework
      remains in its infancy. Here we demonstrate a chemical method which achieves
      dimensionality selection via preferential inhibition of the magnetic exchange in
      an S=1/2 antiferromagnet along one crystal direction, switching the system from
      being quasi-two- to quasi-one-dimensional while effectively maintaining the
      nearest-neighbor coupling strength.

PMID- 22401253
TI  - Spin-orbit sum rule for electric multipole transitions in nonresonant inelastic x
      ray scattering.
AB  - The sum rule for the branching ratio of dipole-excited core-valence transitions
      in isotropic x-ray absorption spectroscopy is extended to electric multipole
      transitions. The derived sum rule not only shows that the branching ratio is
      linearly related to the expectation value of the angular part of the spin-orbit
      operator in the valence states, but also shows a strong dependence on the rank of
      the multipole. The spin-orbit dependence vanishes in the weighted sum over the
      branching ratios. The effect can be an important diagnostic tool for high-energy
      spectroscopies.

PMID- 22401254
TI  - Photoexcitation dynamics in films of C60 and Zn phthalocyanine with a layered
      nanostructure.
AB  - We elucidate photoexcitation dynamics in C(60) and zinc phthalocyanine (ZnPc)
      from picoseconds to milliseconds by transient absorption and time-resolved
      terahertz spectroscopy. Autoionization of C(60) is a precursor to photocarrier
      generation. Decay of the terahertz signal is due to decreasing photocarrier
      mobility over the first 20 ps and thereafter reflects recombination dynamics.
      Singlet diffusion rates in C(60) are determined by modeling the rise of ground
      state bleaching of ZnPc absorption following C(60) excitation. Recombination
      dynamics transform from bimolecular to monomolecular as the layer thickness is
      reduced, revealing a metastable exciplex at the C(60)/ZnPc interface with a
      lifetime of 150 MUs.

PMID- 22401255
TI  - Second-harmonic generation induced by electric currents in GaAs.
AB  - We demonstrate a new, nonlinear optical effect of electric currents. First, a
      steady current is generated by applying a voltage on a doped GaAs crystal. We
      demonstrate that this current induces second-harmonic generation of a probe laser
      pulse. Second, we optically inject a transient current in an undoped GaAs crystal
      by using a pair of ultrafast laser pulses and demonstrate that it induces the
      same second-harmonic generation. In both cases, the induced second-order
      nonlinear susceptibility is proportional to the current density. This effect can
      be used for nondestructive, noninvasive, and ultrafast imaging of currents. These
      advantages are illustrated by the real-time observations of a coherent plasma
      oscillation and spatial resolution of current distribution in a device. This new
      effect also provides a mechanism for electrical control of the optical response
      of materials.

PMID- 22401256
TI  - Signature of a Fano resonance in a plasmonic metamolecule's local density of
      optical states.
AB  - We present measurements on plasmonic metamolecules under local excitation using
      cathodoluminescence which show a spatial redistribution of the local density of
      optical states at the same frequency where a sharp spectral Fano feature in
      extinction has been observed. Our analytical model shows that both near- and far
      field effects arise due to interference of the same two eigenmodes of the system.
      We present quantitative insights both in a bare state, and in a dressed state
      picture that describe Fano interference either as near-field amplitude transfer
      between coupled bare states, or as interference of uncoupled eigenmodes in the
      far field. We identify the same eigenmode causing a dip in extinction to strongly
      enhance the radiative local density of optical states, making it a promising
      candidate for spontaneous emission control.

PMID- 22401257
TI  - Linearly polarized, single-mode spontaneous emission in a photonic nanowire.
AB  - We introduce dielectric elliptical photonic nanowires to funnel efficiently the
      spontaneous emission of an embedded emitter into a single optical mode. Inside a
      wire with a moderate lateral aspect ratio, the electromagnetic environment is
      largely dominated by a single guided mode, with a linear polarization oriented
      along the ellipse major axis. The resulting monomode spontaneous emission is
      maintained over a broad wavelength range, a key asset of this 1D photonic
      structure. Our theoretical analysis is completed by an experimental study of GaAs
      elliptical photonic wires with embedded InAs quantum dots. In particular, the
      fraction of collected photons with the desired linear polarization can exceed
      95%.

PMID- 22401258
TI  - Shape of a ponytail and the statistical physics of hair fiber bundles.
AB  - A general continuum theory for the distribution of hairs in a bundle is
      developed, treating individual fibers as elastic filaments with random intrinsic
      curvatures. Applying this formalism to the iconic problem of the ponytail, the
      combined effects of bending elasticity, gravity, and orientational disorder are
      recast as a differential equation for the envelope of the bundle, in which the
      compressibility enters through an "equation of state." From this, we identify the
      balance of forces in various regions of the ponytail, extract a remarkably simple
      equation of state from laboratory measurements of human ponytails, and relate the
      pressure to the measured random curvatures of individual hairs.

PMID- 22401259
TI  - Filament-length-controlled elasticity in 3D fiber networks.
AB  - We present a model for disordered 3D fiber networks to study their linear and
      nonlinear elasticity. In contrast to previous 2D models, these 3D networks with
      binary crosslinks are underconstrained with respect to fiber stretching
      elasticity, suggesting that bending may dominate their response. We find that
      such networks exhibit a bending-dominated elastic regime controlled by fiber
      length, as well as a crossover to a stretch-dominated regime for long fibers.
      Finally, by extending the model to the nonlinear regime, we show that these
      networks become intrinsically nonlinear with a vanishing linear response regime
      in the limit of flexible or long filaments.

PMID- 22401261
TI  - Base pair openings and temperature dependence of DNA flexibility.
AB  - The relationship of base pair openings to DNA flexibility is examined. Published
      experimental data on the temperature dependence of the persistence length by two
      different groups are well described in terms of an inhomogeneous Kratky-Porot
      model with soft and hard joints, corresponding to open and closed base pairs, and
      sequence-dependent statistical information about the state of each pair provided
      by a Peyrard-Bishop-Dauxois (PBD) model calculation with no freely adjustable
      parameters.

PMID- 22401260
TI  - Biological ferroelectricity uncovered in aortic walls by piezoresponse force
      microscopy.
AB  - Many biological tissues are piezoelectric and pyroelectric with spontaneous
      polarization. Ferroelectricity, however, has not been reported in soft biological
      tissues yet. Using piezoresponse force microscopy, we discover that the porcine
      aortic walls are not only piezoelectric, but also ferroelectric, with the
      piezoelectric coefficient in the order of 1 pm/V and coercive voltage
      approximately 10 V. Through detailed switching spectroscopy mapping and
      relaxation studies, we also find that the polarization of the aortic walls is
      internally biased outward, and the inward polarization switched by a negative
      voltage is unstable, reversing spontaneously to the more stable outward
      orientation shortly after the switching voltage is removed. The discovery of
      ferroelectricity in soft biological tissues adds an important dimension to their
      biophysical properties, and could have physiological implications as well.

PMID- 22401262
TI  - Maxwell stress in fluid mixtures.
AB  - We examine the structure of Maxwell stress in binary fluid mixtures under an
      external electric field and discuss its consequence. In particular, we show that,
      in immiscible blends, it is intimately related to the statistics of domain
      structure. This leads to a compact formula, which may be useful in the
      investigation of electrorheological effects in such systems. The stress tensor
      calculated in a phase separated fluid under a steady electric field is in a good
      agreement with recent experiments.

PMID- 22401263
TI  - Comment on "Heavy cluster knockout reaction 16O(12C,2(12)C)4He and the nature of
      the 12C-12C interaction potential".

PMID- 22401264
TI  - Syntheses and tunable emission properties of 2-alkynyl azulenes.
AB  - Various substituted 2-azulenes have been synthesized via Sonogashira coupling.
      Doping with superacids allows tunable emission from 443 to 750 nm depending on
      the substitution. The proton doped compounds are the first azulene alkyne based
      systems that show emission originating only from the S(1) excited state.

PMID- 22401265
TI  - Electronic structure and optical properties of an alternated fluorene
      benzothiadiazole copolymer: interplay between experimental and theoretical data.
AB  - The donor-acceptor copolymer containing benzothiadiazole (electron acceptor),
      linked to functionalized fluorene (electron donor), [poly[9,9-bis(3'-(tert-butyl
      propanoate))fluorene-co-4,7-(2,1,3-benzothiadiazole)] (LaPPS40), was synthesized
      through the Suzuki route. The polymer was characterized by scanning electron
      microscopy, gel permeation chromatography, NMR, thermal analysis, cyclic
      voltammetry, X-ray photoelectron spectroscopy, UV-vis spectrometry, and
      photophysical measurements. Theoretical calculations (density functional theory
      and semiempirical methodologies) used to simulate the geometry of some oligomers
      and the dipole moments of molecular orbitals involved were in excellent agreement
      with experimental results. Using such data, the higher energy absorption band was
      attributed to the pi-pi* (S(0) -> S(4)) transition of the fluorene units and the
      lower lying band was attributed to the intramolecular (ICT) (S(0) -> S(1)) charge
      transfer between acceptor (benzothiadiazole) and donor groups (fluorene) (D-A
      structure). The ICT character of this band was confirmed by its solvatochromic
      properties using solvents with different dielectric properties, and this behavior
      could be well described by the Lippert-Mataga equation. To explain the
      solvatochromic behavior, both the magnitude and orientation of the dipole moments
      in the electronic ground state and in the excited state were analyzed using the
      theoretical data. According to these data, the change in magnitude of the dipole
      moments was very small for both transitions but the spatial orientation changed
      remarkably for the lower energy band ascribed to the ICT band.

PMID- 22401266
TI  - Gold nanoparticle sensors for detecting chronic kidney disease and disease
      progression.
AB  - AIM: To study the feasibility of a novel nanomedical method that utilizes breath
      testing for identifying chronic kidney disease (CKD) and disease progression.
      MATERIALS & METHODS: Exhaled breath samples were collected from 62 volunteers.
      The breath samples were analyzed using sensors based on organically
      functionalized gold nanoparticles, combined with support vector machine analysis.
      Sensitivity and specificity with reference to CKD patient classification
      according to estimated glomerular filtration rate were determined using cross
      validation. The chemical composition of the breath samples was studied using gas
      chromatography linked with mass spectrometry. RESULTS: A combination of two to
      three gold nanoparticles sensors provided good distinction between early-stage
      CKD and healthy states (accuracy of 79%) and between stage 4 and 5 CKD states
      (accuracy of 85%). A single sensor provided a distinction between early and
      advanced CKD (accuracy of 76%). Several substances in the breath were identified
      and could be associated with CKD-related biochemical processes or with the
      accumulation of toxins through kidney function loss. CONCLUSION: Breath testing
      using gold nanoparticle sensors holds future potential as a cost-effective, fast
      and reliable diagnostic test for early detection of CKD and monitoring of disease
      progression.

PMID- 22401267
TI  - Biocompatibility and bone tissue compatibility of alumina ceramics reinforced
      with carbon nanotubes.
AB  - AIMS: The addition of carbon nanotubes (CNTs) remarkably improves the mechanical
      characteristics of base materials. CNT/alumina ceramic composites are expected to
      be highly functional biomaterials useful in a variety of medical fields.
      Biocompatibility and bone tissue compatibility were studied for the application
      of CNT/alumina composites as biomaterials. METHODS & RESULTS: Inflammation
      reactions in response to the composite were as mild as those of alumina ceramic
      alone in a subcutaneous implantation study. In bone implantation testing, the
      composite showed good bone tissue compatibility and connected directly to new
      bone. An in vitro cell attachment test was performed for osteoblasts,
      chondrocytes, fibroblasts and smooth muscle cells, and CNT/alumina composite
      showed cell attachment similar to that of alumina ceramic. DISCUSSION &
      CONCLUSION: Owing to proven good biocompatibility and bone tissue compatibility,
      the application of CNT/alumina composites as biomaterials that contact bone, such
      as prostheses in arthroplasty and devices for bone repair, are expected.

PMID- 22401268
TI  - Activated carbon fibers with a high heteroatom content by chemical activation of
      PBO with phosphoric acid.
AB  - The preparation of activated carbon fibers (ACFs) by phosphoric acid activation
      of poly(p-phenylene benzobisoxazole) (PBO) fibers was studied, with particular
      attention to the effects of impregnation ratio and carbonization temperature on
      porous texture. Phosphoric acid has a strong effect on PBO degradation, lowering
      the temperature range at which the decomposition takes place and changing the
      number of mass loss steps. Chemical analysis results indicated that activation
      with phosphoric acid increases the concentration of oxygenated surface groups;
      the resulting materials also exhibiting high nitrogen content. ACFs are obtained
      with extremely high yields; they have well-developed porosity restricted to the
      micropore and narrow mesopore range and with a significant concentration of
      phosphorus incorporated homogeneously in the form of functional groups. An
      increase in the impregnation ratio leads to increases in both pore volume and
      pore size, maximum values of surface area (1250 m(2)/g) and total pore volume
      (0.67 cm(3)/g) being attained at the highest impregnation ratio (210 wt %
      H(3)PO(4)) and lowest activation temperature (650  degrees C) used; the
      corresponding yield was as large as 83 wt %. The obtained surface areas and pore
      volumes were higher than those achieved in previous works by physical activation
      with CO(2) of PBO chars.

PMID- 22401269
TI  - Sources and pathways of nutrients in the semi-arid region of Beijing-Tianjin,
      China.
AB  - Semiarid regions worldwide are particularly prone to eutrophication, which causes
      immense ecological and economic problems. One region that is in transition and
      requires systematic research for effective intervention is the dry landscape of
      Beijing-Tianjin (P. R. China). We investigated the sources and spatiotemporal
      loads of nitrogen and phosphorus species over a one-year period in the Haihe
      catchment that drains the megacity of Beijing. Although wastewater treatment was
      improved in recent years, the rivers were heavily contaminated by 0.3-5.3 mg P L(
      1) and 3.0-49 mg N L(-1), with toxic levels of nitrite (>=1 mg NO(2)-N L(-1)) and
      ammonia (>=0.6 mg NH(3)-N L(-1)). The average NH(4)(+) (16.9 mg N L(-1))
      increased by 160% compared to 1996-levels. Mass fluxes and delta(15)N-signatures
      revealed that nutrients originated almost exclusively from sewage. Furthermore,
      the water balance demonstrated that >90% of the polluted river water was diverted
      for irrigation, thereby threatening food safety and groundwater quality. Per
      capita loads of 1.42 kg N/yr and 115 g P/yr were comparable to the peak
      discharges typical of Europe and the United States in 1970-1990, but
      concentrations were 2-3 times higher in the Beijing-Tianjin region. Our research
      identified sewage as the predominant nutrient source in this semiarid region,
      which suggests that state-of-the-art wastewater treatment would drastically
      mitigate eutrophication and even more rapidly than was previously observed in
      Europe.

PMID- 22401270
TI  - Clonal dissemination of Salmonella enterica serovar Infantis in Germany.
AB  - Salmonella enterica serovar Infantis (Salmonella Infantis) is consistently
      isolated from broiler chickens, pigs, and humans worldwide. This study
      investigated 93 epidemiologically unrelated Salmonella Infantis strains isolated
      in Germany between 2005 and 2008 in respect to their transmission along the food
      chain. Various phenotypic and genotypic methods were applied, and the
      pathogenicity and resistance gene repertoire was determined. Phenotypically, 66%
      of the strains were susceptible to all 17 antimicrobials tested, while the others
      were almost all multidrug-resistant (two or more antimicrobial resistances), with
      different resistance profiles and preferentially isolated from broiler chickens.
      A number of phage types (PTs) were shared by strains from pigs, broiler chickens,
      and humans (predominated by PT 29). One, PT 1, was only detected in strains from
      pigs/pork and humans. Pulsed-field gel electrophoresis (PFGE) subdivided strains
      in seven different clusters, named A-G, consisting of 35 various XbaI profiles
      with coefficient of similarity values of 0.73-0.97. The majority of XbaI profiles
      were assigned to clusters A and C, and two predominant XbaI profiles were common
      in strains isolated from all sources investigated. Multi-locus sequence typing
      (MLST) analysis of selected strains representing the seven PFGE clusters revealed
      that they all belonged to ST32. The pathogenicity gene repertoire of 37
      representative Salmonella Infantis strains analyzed by microarray was also
      identical. The resistance gene repertoire correlated perfectly with the
      phenotypic antimicrobial resistance profiles, and multidrug-resistant strains
      were associated with class 1 integrons. Overall, this study showed that two major
      closely related genotypes of Salmonella Infantis can transmit in Germany to
      humans through contaminated broiler meat or pork, and consequently presents a
      hazard for human health.

PMID- 22401271
TI  - In vitro adherence patterns of Shigella serogroups to bovine recto-anal junction
      squamous epithelial (RSE) cells are similar to those of Escherichia coli O157.
AB  - The aims of this study were to determine whether Shigella species, which are
      human gastrointestinal pathogens, can adhere to cattle recto-anal junction
      squamous epithelial (RSE) cells using a recently standardized in vitro adherence
      assay, and to compare their adherence patterns with that of Escherichia coli
      O157. Shigella dysenteriae (serogroup A), S. flexneri (serogroup B), S. boydii
      (serogroup C), and S. sonnei (serogroup D) were tested in adherence assays using
      both RSE and HEp-2 cells, in the presence or absence of D+mannose. Escherichia
      coli O157, which adheres to RSE cells in a Type I fimbriae-independent manner,
      was used as a positive control. Shigella serogroups A, B, D, but not C adhered to
      RSE cells with distinct adherence patterns in the presence of D+mannose. No such
      distinction could be made between the four Shigella serogroups based on the HEp-2
      cell adherence patterns. Thus, this study provides evidence that certain Shigella
      serogroups adhere to RSE cells in a manner that is similar to the adherence
      pattern of E. coli O157. These unexpected observations of in vitro binding of
      these foodborne human pathogens to cells of the bovine gastrointestinal tract
      warrant evaluation of Shigella carriage by cattle using both experimental and
      observational studies, especially for serogroups B and D. Such studies are
      currently underway.

PMID- 22401272
TI  - Is there a difference in subjective experience of cognitive function in patients
      with unipolar disorder versus bipolar disorder?
AB  - BACKGROUND: Cognitive dysfunction in unipolar disorder (UD) and bipolar disorder
      (BD) may persist into remission and affect psychosocial function. Executive and
      memory deficits during remission may be more pronounced in BD than UD. However,
      patients' subjective experience of cognitive difficulties is poorly understood,
      and it is unclear whether BD and UD patients experience different cognitive
      difficulties. AIMS: To investigate whether there are differences in the quality
      and magnitude of subjective cognitive difficulties between UD and BD, and which
      factors influence the subjective cognitive difficulties in these patients.
      METHODS: Patients with BD (n = 54) or UD (n = 45) were referred to the outpatient
      mood disorder clinic at Department of Psychiatry, Copenhagen University Hospital,
      following hospital discharge. Affective symptoms and patients' experience of
      cognitive symptoms were assessed at their initial consultation at the clinic.
      RESULTS: Patients experienced mild to moderate cognitive impairment despite being
      in partial or full remission, but there were no differences in subjective
      difficulties between BD and UD. Subjective cognitive dysfunction was predicted by
      depression severity, anxiety and mania symptoms rather than by diagnosis, age,
      gender or alcohol misuse. CONCLUSION: The absence of difference in subjective
      cognitive difficulties between UD and BD contrasts with evidence of greater
      objective dysfunction in BD. This highlights a potential discord between
      subjective and objective measures of cognitive function. Subjective cognitive
      function was predicted by affective symptoms, perhaps suggesting that this
      reflects mood symptoms rather than objective deficits. This points to a clinical
      need for objective assessment of cognitive function in these patient groups.

PMID- 22401273
TI  - Relationship between the timing of prostaglandin-induced luteolysis and effects
      on the conceptus during early pregnancy in mares.
AB  - To advance the understanding of early pregnancy and pregnancy failure in horses,
      this study determined how luteolysis induced by cloprostenol (an analogue of
      prostaglandin F2alpha) affects conceptus development. Mares were injected on Days
      12, 14, 16 or 18 of pregnancy with either cloprostenol (treatment groups, total
      n=83 pregnancies) or saline (controls, n=81), and growth of the conceptuses was
      monitored and compared by daily ultrasonography until they were collected
      transcervically on Days 15-22, 1-4 days after the injections. The comparisons
      were extended in the recovered conceptuses by counting somites, measuring the
      volume and osmolality of yolk-sac fluid and its concentrations of proteins,
      estrone sulfate and progesterone, and by assessing the morphology of the capsule
      and vascular system. When luteolysis was initiated on or before Day 16, most
      pregnancies survived until the time of collection and the conceptuses in
      respective treated and control groups on Days 15-20 were very similar except for
      some effects of treatment on the capsule and vascular development. In contrast,
      after luteolysis was initiated on Day 18, abortion often ensued within 3 days and
      most conceptuses collected had degenerated, therein constituting a predictable
      system in which to study the pathogenesis of a particular cause of pregnancy
      failure.

PMID- 22401274
TI  - Ontogenesis of phase I hepatic drug metabolic enzymes in sheep.
AB  - Cytochrome P450 (CYP) enzymes are important for the metabolism of many drugs.
      While there is information on their identity and ontogeny in humans and rodents,
      similar data in sheep are lacking. In the present study, cDNA sequences of
      several CYP enzymes (CYP2A6, CYP2C19, CYP2D6) were cloned by rapid amplification
      of cDNA ends. In adult, newborn and fetal sheep the mRNA and protein levels of
      these CYPs and the regulatory factor, hepatic nuclear factor 4alpha (HNF4alpha)
      were determined in liver samples using real-time PCR and western blotting. The
      effect of antenatal glucocorticoid on these enzymes was also studied by i.v.
      infusion of cortisol (0.45 mgh(-1); 80 h) to another group of fetuses. The mRNA
      and protein levels of the CYPs and HNF4alpha were low or absent in the fetus,
      followed by increasing levels in the newborn and adult. Fetal cortisol
      administration significantly increased the mRNA and protein levels of CYP2D6.
      Moreover, the correlation observed between the CYP and HNF4alpha mRNA levels
      suggests a possible regulatory role for this transcription factor. The findings
      suggest that fetal and newborn lambs have a low ability to metabolise drugs that
      are substrates of these enzymes, and that this ability increases with advancing
      postnatal age, similar to the situation in humans.

PMID- 22401275
TI  - Evidence of the genetic trend for secondary sex ratio in Iranian Holsteins.
AB  - Calving records from the Animal Breeding Center of Iran collected from January
      2000 to December 2007 and comprising 520964 Holstein calving events from 2135
      herds were analysed using animal and sire models to estimate variance components,
      heritabilities and genetic trends for secondary sex ratio (SSR) in the first,
      second and third parities. Direct heritabilities for SSR ranged from 0.00004 to
      0.001 over the parities. The linear sire model estimate of heritabilities for SSR
      in the present study was from 0.0002 to 0.0008 over the parities. There were
      positive phenotypic and genetic trends for female rate in Iranian Holsteins over
      the years. Exploitable genetic variation in SSR can take advantage of sexual
      dimorphism for economically important traits, which may facilitate greater
      selection intensity and thus greater response to selection, as well as reducing
      the replacement costs. On the other hand, increasing genetic and phenotypic
      trends for female rate in the population under study could be partly assigned to
      increased use of new reproductive technologies in dairy herds; therefore, dairy
      farmers have the option to select from among their herd's potential dams and
      produce dairy replacement heifers from only the genetically superior animals,
      thus promoting enhanced rates of genetic gain.

PMID- 22401276
TI  - Glucose and glycine synergistically enhance the in vitro development of porcine
      blastocysts in a chemically defined medium.
AB  - In the present study, the effects of glucose and/or glycine on the in vitro
      development of Day 5 (Day 0=IVF) porcine blastocysts were determined. The
      addition of 2.5-10 mM glucose to the chemically defined culture medium porcine
      zygote medium (PZM)-5 significantly increased blastocyst survival rates compared
      with those of blastocysts cultured in the absence of glucose. The addition of 5
      and 10 mM glycine to PZM-5 containing 5 mM glucose significantly enhanced the
      development to hatching and the number of hatched blastocysts compared with no
      addition of glycine. However, the addition of glycine to PZM-5 with no glucose
      did not improve blastocyst development. The ATP content of Day 6 blastocysts
      cultured with glucose was significantly higher than that of blastocysts cultured
      in the absence of glucose, regardless of glycine supplementation. The diameter
      and total cell numbers were significantly greater, and the apoptotic index was
      significantly lower, in Day 6 blastocysts cultured with both glucose and glycine.
      These results indicate that glucose is an important energy source for the porcine
      blastocyst and that glucose and glycine act synergistically to enhance
      development to the hatching and hatched blastocyst stage in vitro.

PMID- 22401277
TI  - Reproductive performance and fertility in male and female adult mice chronically
      treated with hexarelin.
AB  - Hexarelin (HEXr), a synthetic ghrelin analogue, has been associated with
      modifications of reproductive physiology. In previous studies of adult mice, we
      detected that HEXr induced significantly reduced ovulation rate and significant
      correlation coefficients between sexual maturation and corporal weight in
      offspring. In this study, we investigated the effects of chronic HEXr
      administration on sperm concentration and functional activity, oestrous cyclicity
      and pregnancy index, in addition to the number of fetuses and its correlation
      with the number of corpora lutea. Adult Albino swiss mice were injected (sc)
      daily with HEXr: 100 MUgkg(-1) day(-1) (HEXr D1) or 200 MUgkg(-1) day(-1) (HEXr
      D2) for 53 days in males and 30 days in females. We detected a significantly
      decreased ratio in the number of fetuses per corpora lutea in females treated
      with HEXr D2 for 30 days before mating and during the first 6 days of pregnancy,
      in addition to a downward trend in the pregnancy index and percentage of females
      impregnated by each male treated with both doses of the analogue. Although we did
      not find any significant effect on additional parameters evaluated in both
      genders, we propose certain effects of HEXr on the implantation process and/or
      early development of embryos and over the in vivo reproductive capability of
      males.

PMID- 22401278
TI  - Follicle development in cryopreserved bitch ovarian tissue grafted to
      immunodeficient mouse.
AB  - The present study evaluated: (1) in vivo follicular development in canine ovarian
      tissue after slow freezing and xenotransplantation; and (2) the use of
      erythropoietin (EPO) as an angiogenic factor to optimise the transplantation
      procedure. Frozen-thawed ovarian tissue from five bitches was grafted into severe
      combined immunodeficient (SCID) mice (n=47) treated with or without EPO (500 IU
      kg(-1), once daily for 3 days) (Groups A and B, respectively) and analysed after
      0, 1, 8 or 16 weeks. Follicle grade, follicle density, follicle morphology and
      stromal cells density were assessed by histological analysis, whereas
      vascularisation of the graft was quantified by immunohistochemistry with anti
      alpha-smooth muscle actin antibody. Despite a massive loss of follicles after
      grafting, secondary follicle density was higher at 8 and 16 weeks than at 1 week
      regardless of EPO treatment. EPO significantly improved early follicle morphology
      and stromal cell density after 8 weeks and blood vessel density at 16 weeks after
      transplantation (P<0.05). Intact secondary follicles with more than three
      granulosa cells layers were observed 16 weeks after transplantation. The results
      suggest that canine ovarian tissue can be successfully preserved by our slow
      freezing protocol because the tissue showed follicular growth after
      xenotransplantation. EPO treatment did not lessen the massive loss of follicles
      after transplantation.

PMID- 22401279
TI  - Effects of human chorionic gonadotrophin administration on day 5 after oestrus on
      corpus luteum characteristics, circulating progesterone and conceptus elongation
      in cattle.
AB  - The aim of the present study was to test the hypothesis that elevated
      concentrations of progesterone (P4) resulting from the induction of an accessory
      corpus luteum (CL) by human chorionic gonadotrophin (hCG) administration on day 5
      after oestrus would lead to advanced conceptus elongation on day 14 following
      embryo transfer on day 7. The oestrous cycles of cross-bred beef heifers were
      synchronised and animals were randomly assigned to receive either of two
      treatments: (1) intramuscular injection of 3000 IU hCG on day 5 after oestrus
      (n=14); or (2) intramuscular injection of saline on day 5 after oestrus (n=13).
      Ovaries were scanned daily by transrectal ultrasonography to assess CL
      development. Serum concentrations of P4 were determined from daily blood samples
      collected from the jugular vein. In vitro-produced bovine blastocysts were
      transferred to synchronised recipients on day 7 after oestrus (n=15 blastocysts
      per recipient). Heifers were killed on day 14 after oestrus and the uterus was
      flushed to recover the embryos. Injection of hCG on day 5 induced ovulation of
      the dominant follicle in all treated heifers and increased the total area of
      luteal tissue on the ovary, which was associated with a significant increase
      (P<0.001) in serum concentrations of P4 from day 7 to day 14. Positive
      associations were detected between circulating P4 with CL area (within-day
      correlations ranging from r=0.45 to r=0.67) and total area of luteal tissue
      (within-day correlations ranging from r=0.65 to r=0.86) Administration of hCG did
      not affect the proportion of day 14 conceptuses recovered. However, compared with
      the control group, hCG-treated heifers had increased conceptus length (3.91+/
      1.23 vs. 5.57+/-1.02 mm, respectively; P=0.06), width (1.00+/-0.06 vs. 1.45+/
      0.05 mm, respectively; P=0.002) and area (5.71+/-0.97 vs. 8.31+/-0.83,
      respectively; P=0.02). Although numerically greater, mean interferon-tau (IFNT)
      production in vitro did not differ significantly (P=0.54) between embryos
      recovered from hCG-treated and control heifers. In contrast, there was a strong
      positive correlation between individual embryo length (r=0.76; P<0.001) and
      individual embryo area (r=0.72; P<0.001) and IFNT production. In conclusion,
      administration of hCG on day 5 after oestrus resulted in the formation of an
      accessory CL and hypertrophy of the original CL, the result of which was an
      increase in P4 concentrations from day 7 onwards. These elevated P4
      concentrations were associated with an increased conceptus area. Furthermore,
      conceptus size was highly correlated with IFNT secretion in vitro.

PMID- 22401280
TI  - Epidermal growth factor upregulates endometrial CYR61 expression via activation
      of the JAK2/STAT3 pathway.
AB  - Endometrial cysteine-rich protein 61 (CYR61, CCN1) is a growth factor-inducible
      gene whose expression is elevated during the proliferative phase of the menstrual
      cycle and which has been implicated in the pathogenesis of endometriosis. This
      study aimed to define the mediators of epidermal growth factor (EGF) signalling
      on CYR61 expression in spontaneously immortalised human endometrial epithelial
      cells (HES) as a model system. After 30 min of EGF treatment, the receptor was
      phosphorylated and internalised as well as mRNA CYR61 increased in HES cells.
      However, neither inhibition of C-terminal EGF receptor (EGFR)-phosphorylation nor
      blockage of the mitogen-activated proteinkinase/extracellular signal-regulated
      kinase (MAPK/ERK) pathway was able to reduce CYR61 levels. Surprisingly, the HES
      cells showed upregulation of CYR61 mRNA expression after inhibition of the
      MAPK/ERK pathway when treated with EGF. Specific inhibitor studies identified the
      contribution of Janus kinase 2 (JAK2) and the signal transducer and activator of
      transcription protein STAT3 to the regulation of CYR61 expression. The JAK2/STAT3
      interaction contributed to the basal expression of CYR61 and mediated EGF-driven
      regulation of CYR61 after 30 and 120 min of treatment. In summary, EGF-mediated
      CYR61 upregulation in HES cells involves STAT3 and is counter-regulated by the
      EGFR/MAPK/ERK pathway.

PMID- 22401281
TI  - Bovine dominant follicular fluid promotes the in vitro development of goat
      preantral follicles.
AB  - The aim of this study was to evaluate the effect of follicular fluid collected
      from bovine dominant follicles (bFF) on the in vitro development of goat
      preantral follicles and determine the best time to add this supplement to the
      culture medium. The preantral follicles were isolated and randomly distributed
      into four treatments in absence (control) or presence of 10% of bFF added on Days
      0 (FF0-18), 6 (FF6-18) or 12 (FF12-18) of culture onwards. After 18 days,
      follicular development was assessed based on follicular survival, antral cavity
      formation, increased follicular diameter as well as fully grown oocyte (>110 MUm)
      viability and meiosis resumption. The oocytes from the cultured follicles were in
      vitro-matured and processed for fluorescence or ultrastructural analysis. The
      results showed that on Day 18 the treatment FF0-18 had a significantly higher
      (P<0.05) survival than control and FF12-18, but not FF6-18. The addition of bFF
      at the beginning of culture (FF0-18 and FF6-18) promoted a high percentage of
      follicular growth, meiosis resumption and early antrum formation. Moreover, this
      study described for the first time the ultrastructural analysis of caprine
      oocytes grown in vitro. This evaluation revealed that in the presence of bFF on
      (FF0-18) the in vitro-grown oocytes presented normal organelle distribution and
      well-defined, intact plasma and nuclear membranes. In conclusion, bFF originating
      from dominant follicles maintain the survival and promote the in vitro growth of
      goat preantral follicles when added at the beginning of culture.

PMID- 22401282
TI  - High levels of mitochondrial heteroplasmy modify the development of ovine-bovine
      interspecies nuclear transferred embryos.
AB  - To investigate the effect of mitochondrial heteroplasmy on embryo development,
      cloned embryos produced using bovine oocytes as the recipient cytoplasm and ovine
      granulosa cells as the donor nuclei were complemented with 2pL mitochondrial
      suspension isolated from ovine (BOOMT embryos) or bovine (BOBMT embryos)
      granulosa cells; cloned embryos without mitochondrial injection served as the
      control group (BO embryos). Reverse transcription-quantitative polymerase chain
      reaction (RT-qPCR) and sodium bisulfite genomic sequencing were used to analyse
      mRNA and methylation levels of pluripotency genes (OCT4, SOX2) and mitochondrial
      genes (TFAM, POLRMT) in the early developmental stages of cloned embryos. The
      number of mitochondrial DNA copies in 2pL ovine-derived and bovine-derived
      mitochondrial suspensions was 960+/-110 and 1000+/-120, respectively. The
      blastocyst formation rates were similar in BOBMT and BO embryos (P>0.05), but
      significantly higher than in BOOMT embryos (P<0.01). Expression of OCT4 and SOX2,
      as detected by RT-qPCR, decreased significantly in BOOMT embryos (P<0.05),
      whereas the expression of TFAM and POLRMT increased significantly, compared with
      expression in BOOMT and BO embryos (P<0.05). In addition, methylation levels of
      OCT4 and SOX2 were significantly greater (P<0.05), whereas those of TFAM and
      POLRMT were significantly lower (P<0.01), in BOOMT embryos compared with BOBMT
      and BO embryos. Together, the results of the present study suggest that the
      degree of mitochondrial heteroplasmy may affect embryonic development.

PMID- 22401283
TI  - The cardiopulmonary haemodynamic transition at birth is not different between
      male and female preterm lambs.
AB  - Males born preterm are at greater risk of illness and death than females,
      principally due to respiratory disease. Much of the excess morbidity occurs
      within the first few hours of life. Therefore, the aim of the present study was
      to investigate whether or not differences in the cardiopulmonary transition soon
      after birth underlie the increased morbidity in males after preterm birth. Nine
      female and thirteen male lambs (128+/-2 days gestation) underwent surgery
      immediately before delivery for implantation of a pulmonary arterial flow-probe
      and catheters into the main pulmonary artery and a carotid artery. After birth
      lambs were ventilated for 30 min (tidal volume 7 mL kg(-1)) while anaesthetised.
      Arterial pressures and flows were recorded in real time and left-ventricular
      output measured using Doppler echocardiography. Before birth, fetal
      cardiopulmonary haemodynamics, arterial blood gases, pH, glucose and lactate did
      not differ between sexes. Similarly, in the neonatal period there were no
      significant differences in arterial blood gas status, ventilation parameters,
      respiratory indices or cardiopulmonary haemodynamics between the sexes. Our data
      show that the cardiopulmonary transition at birth in ventilated, anaesthetised
      preterm lambs is not influenced by sex. Thus, the neonatal 'male disadvantage' is
      not explained by an impaired cardiovascular transition at birth.

PMID- 22401284
TI  - Seminal plasma enhances and accelerates progesterone-induced decidualisation of
      human endometrial stromal cells.
AB  - In preparation for embryo implantation, endometrial stromal cells (ESC) undergo
      differentiation, termed decidualisation. Enhancing endometrial decidualisation
      may overcome reduced endometrial receptivity, a major limiting factor in natural
      and assisted reproduction. To determine whether seminal plasma (SP) influences
      decidualisation, primary human ESC were treated with progesterone (P4, 50 ng mL(
      1)) in the presence or absence of dialysed SP (0.5%) for 24 h or for up to 27
      days to investigate immediate early effects or the effects of prolonged exposure,
      respectively. Combined SP and P4 treatment induced ESC morphological
      differentiation. Relative to control, P4 alone, and SP alone combined treatment
      with SP and P4 for 27 days significantly upregulated mRNA levels of the decidua
      specific markers prolactin (PRL) and insulin-like growth factor binding protein 1
      (IGFBP1). Consistently, PRL protein secretion was significantly increased over
      the course of 27 days combined SP and P4 treatment relative to control, P4 alone
      and SP alone. Likewise, IGFBP1 secretion was significantly greater relative to
      control and P4 alone over the course of 27 days. Thus, SP enhances and
      accelerates P4-mediated decidualisation of human ESC and may enhance endometrial
      receptivity.

PMID- 22401285
TI  - Focal brain lesions to critical locations cause widespread disruption of the
      modular organization of the brain.
AB  - Although it is generally assumed that brain damage predominantly affects only the
      function of the damaged region, here we show that focal damage to critical
      locations causes disruption of network organization throughout the brain. Using
      resting state fMRI, we assessed whole-brain network structure in patients with
      focal brain lesions. Only damage to those brain regions important for
      communication between subnetworks (e.g., "connectors")--but not to those brain
      regions important for communication within sub-networks (e.g., "hubs")--led to
      decreases in modularity, a measure of the integrity of network organization.
      Critically, this network dysfunction extended into the structurally intact
      hemisphere. Thus, focal brain damage can have a widespread, nonlocal impact on
      brain network organization when there is damage to regions important for the
      communication between networks. These findings fundamentally revise our
      understanding of the remote effects of focal brain damage and may explain
      numerous puzzling cases of functional deficits that are observed following brain
      injury.

PMID- 22401286
TI  - Human brain activity predicts individual differences in prior knowledge use
      during decisions.
AB  - Studies by cognitive psychologists, psychophysicists, neuroscientists, and
      economists provide ample evidence that humans use prior knowledge to bias
      decisions adaptively. In this study, we sought to locate and investigate the
      brain areas mediating this behavior. Participants viewed ambiguous abstract
      shapes and decided whether a shape was of Category A (smoother) or B (bumpier).
      The decision was made in the context of one of two prior knowledge cues, 80/20
      and 50/50. The 80/20 cue indicated that upcoming shapes had an 80% probability of
      being of one category, for example, B, and a 20% probability of being of the
      other. The 50/50 cue indicated that upcoming shapes had an equal probability of
      being of either category. The shift in bias produced by the 80/20 cue relative to
      the 50/50 cue was of the predicted sign for every subject but varied in
      magnitude. We searched for brain regions in which activity changes correlated
      with the extent of the bias shift; these were dorsolateral pFC (middle frontal
      gyrus), inferior frontal junction, anterior insula, inferior parietal lobule,
      intraparietal sulcus, head of the caudate, posterior cingulate cortex, and
      fusiform gyrus. The findings indicate that an individual's brain activity in
      these regions reflects the extent to which that individual makes use of prior
      knowledge to bias decisions. We also created within-ROI tuning curves by binning
      the shape curvature levels and plotting brain activity levels at each of the nine
      bins. In the fronto-parietal and anterior insula ROIs, the tuning curves peaked
      at targets contraindicated by the prior knowledge cue (e.g., Category B targets
      if the 80/20 cue meant 20% probability B). The increased activity in these
      regions likely indicates a no-go response when sufficient perceptual evidence
      favored the alternative contraindicated by the 80/20 cue.

PMID- 22401287
TI  - TMS of the FEF interferes with spatial conflict.
AB  - In the Simon task, a conflict arises because irrelevant spatial information
      competes for response selection either facilitating or interfering with
      performance. Responses are faster when stimulus and response position correspond
      than when they do not. The FEFs, which have long been characterized for their
      role in oculomotor control, are also involved in the control of visuospatial
      attention when eye movements are not required. This study was aimed at
      investigating whether the FEFs contribute to spatial conflict. Double-pulse TMS
      was applied to the FEF of either left or right hemisphere during the execution of
      a Simon task at different time windows after the onset of the visual stimulus. A
      suppression of the Simon effect was observed after stimulation of the FEF for
      stimuli appearing in the contralateral hemifield when TMS was applied to the left
      hemisphere after stimulus onset (0-40 and 40-80 msec). A reduction of the
      correspondence effect was observed after right FEF TMS for stimuli presented in
      the left visual hemifield when stimulation was delivered in the 80-120 msec range
      after stimulus onset. These outcomes indicate that the FEF play a critical role
      in encoding spatial attribute of a stimulus for response priming, which is the
      prerequisite for response conflict in the Simon task. Moreover, our finding that
      the left FEF have a dominant role during spatial conflict extends the idea of the
      left-hemisphere lateralization of the motor network in action selection by
      suggesting that the FEF may constitute part of this network.

PMID- 22401288
TI  - Dissociative effects of methylphenidate in nonhuman primates: trade-offs between
      cognitive and behavioral performance.
AB  - Low doses of methylphenidate reduce hyperactivity and improve attention in
      individuals with attention deficit hyperactivity disorder (ADHD) as well as in
      healthy humans and animals. Despite its extensive use, relatively little is known
      about its mechanisms of action. This study investigated the effects of
      methylphenidate on working memory performance, impulsivity, response accuracy and
      precision, and the ability to stay on task in rhesus monkeys using an oculomotor
      delayed response task. Methylphenidate affected task performance in an inverted-U
      manner in all three subjects tested. The improvements resulted from a reduction
      in premature responses and, importantly, not from improvement in the memory of
      target location. The length of time subjects participated in each session was
      also affected dose dependently. However, the dose at which the length of
      participation was maximally increased significantly impaired performance on the
      working memory task. This dissociation of effects has implications for the
      treatment of ADHD, for the nonprescription use of methylphenidate for cognitive
      enhancement, and for furthering the basic understanding of the neural substrate
      underlying these processes.

PMID- 22401289
TI  - Typhoid intestinal perforations at a University teaching hospital in Northwestern
      Tanzania: A surgical experience of 104 cases in a resource-limited setting.
AB  - BACKGROUND: Typhoid intestinal perforation is still prevalent in many developing
      countries. Despite the advances in the management, the outcome in these patients
      in resource limited countries is still very poor. This study was to review our
      experiences on the surgical management of typhoid intestinal perforation and to
      determine the prognostic factors for mortality in our local setting. METHODS:
      This was a combined retrospective and prospective study of patients who were
      operated for typhoid intestinal perforation at Bugando Medical Centre between
      August 2006 and September 2011. Data collected were analyzed using SPSS computer
      software version 15. RESULTS: A total of 104 patients were studied representing
      8.7% of typhoid fever cases. Males were affected twice more than the females
      (2.6:1). Their ages ranged from 8 to 76 years with a median age of 18.5 years.
      The peak age incidence was in the 11-20 years age group. Fever and abdominal pain
      were the most common presenting symptoms and majority of the patients (80.8%)
      perforated between within 14 days of illness. Chest and abdominal radiographs
      revealed pneumoperitonium in 74.7% of cases. Ultrasound showed free peritoneal
      collection in 85.7% of cases. Nine (10.2%) patients were HIV positive with a
      median CD4+ count of 261 cells/MUl. The perforation-surgery interval was more
      than 72 hours in 90(86.5%) patients. The majority of patients (84.6%) had single
      perforations and ileum was the most common part of the bowel affected occurring
      in 86.2% of cases. Simple closure of the perforations was the most commonly
      performed procedure accounting for 78.8% of cases. Postoperative complication
      rate was 39.4% and surgical site infection was the most frequent complication in
      55.5% of cases. Mortality rate was 23.1% and it was statistically significantly
      associated with delayed presentation, inadequate antibiotic treatment prior to
      admission, shock on admission, HIV positivity, low CD4 count (< 200 cells/MUl),
      high ASA classes (III-V), delayed operation, multiple perforations, severe
      peritoneal contamination and presence of postoperative complications (P < 0.001).
      The median overall length of hospital stay was 28 days. CONCLUSION: Typhoid
      intestinal perforation is still endemic in our setting and carries high morbidity
      and mortality. This study has attempted to determine the factors that
      statistically influence mortality in typhoid perforation in our environment.
      Appropriate measures focusing at these factors are vital in order to deliver
      optimal care for these patients in this region.

PMID- 22401290
TI  - Does perceived burdensomeness erode meaning in life among older adults?
AB  - BACKGROUND: Identification of risk factors for the loss of meaning in life among
      older adults is needed. In this article, we test hypotheses derived from the
      Interpersonal Theory of Suicide concerning the role of perceptions that one is a
      burden on others as a risk factor for lower meaning in life. METHODS: A
      prospective design was used to examine the temporal associations between
      perceptions of burdensomeness on others and perceived meaning in life among older
      adults (n=65) seeking mental health treatment (primarily for depression and/or
      anxiety) at an outpatient geriatric mental health clinic. Participants completed
      self-report questionnaires within a month following intake. Follow-up
      questionnaires were completed over the phone two months later. RESULTS: Perceived
      burdensomeness predicted lack of meaning in life two months later, while
      accounting for depression severity. In contrast, baseline levels of meaning in
      life did not significantly predict the levels of burdensomeness at two months.
      CONCLUSION: The findings suggest that burdensomeness may contribute to suicide
      morbidity and mortality in late-life by eroding meaning in life. Empirically
      supported treatments for late-life depression could be adapted to focus on
      perceptions of burdensomeness and its connections with meaning in life.

PMID- 22401292
TI  - Photoswitchable azoheterocycles via coupling of lithiated imidazoles with
      benzenediazonium salts.
AB  - In contrast to azobenzenes, heterocyclic azo compounds are less well
      investigated. Phenylazoimidazoles would be versatile as photodissociable ligands
      (PDLs) because imidazole is an important donor in coordination chemistry. Here,
      we present the synthesis of 4- and 5-phenylazoimidazoles via a novel azo-coupling
      method. 1,2-Protected imidazole is lithiated in the 5-position and coupled with
      benzenediazonium tetrafluoroborate. Several new phenylazoimidazoles were
      prepared. They exhibit an excellent switching behavior. Upon irradiation of the
      trans isomers with UV light, >95% of the cis forms are obtained. Upon heating, a
      complete transformation back to the trans configuration was achieved. Back
      switching with visible light, however, is incomplete.

PMID- 22401291
TI  - Comparative genomics and transcriptional profiles of Saccharopolyspora erythraea
      NRRL 2338 and a classically improved erythromycin over-producing strain.
AB  - BACKGROUND: The molecular mechanisms altered by the traditional mutation and
      screening approach during the improvement of antibiotic-producing microorganisms
      are still poorly understood although this information is essential to design
      rational strategies for industrial strain improvement. In this study, we applied
      comparative genomics to identify all genetic changes occurring during the
      development of an erythromycin overproducer obtained using the traditional mutate
      and- screen method. RESULTS: Compared with the parental Saccharopolyspora
      erythraea NRRL 2338, the genome of the overproducing strain presents 117
      deletion, 78 insertion and 12 transposition sites, with 71 insertion/deletion
      sites mapping within coding sequences (CDSs) and generating frame-shift
      mutations. Single nucleotide variations are present in 144 CDSs. Overall, the
      genomic variations affect 227 proteins of the overproducing strain and a
      considerable number of mutations alter genes of key enzymes in the central carbon
      and nitrogen metabolism and in the biosynthesis of secondary metabolites,
      resulting in the redirection of common precursors toward erythromycin
      biosynthesis. Interestingly, several mutations inactivate genes coding for
      proteins that play fundamental roles in basic transcription and translation
      machineries including the transcription anti-termination factor NusB and the
      transcription elongation factor Efp. These mutations, along with those affecting
      genes coding for pleiotropic or pathway-specific regulators, affect global
      expression profile as demonstrated by a comparative analysis of the parental and
      overproducer expression profiles. Genomic data, finally, suggest that the mutate
      and-screen process might have been accelerated by mutations in DNA repair genes.
      CONCLUSIONS: This study helps to clarify the mechanisms underlying antibiotic
      overproduction providing valuable information about new possible molecular
      targets for rationale strain improvement.

PMID- 22401293
TI  - Linking energy production and protein synthesis in hydrogenotrophic methanogens.
AB  - Hydrogenotrophic methanogens possessing the hydrogen-dependent dehydrogenase Hmd
      also encode paralogs of this protein whose function is poorly understood. Here we
      present biochemical evidence that the two inactive Hmd paralogs of
      Methanocaldococcus jannaschii, HmdII and HmdIII, form binary and ternary
      complexes with several components of the protein translation apparatus. HmdII and
      HmdIII, but not the active dehydrogenase Hmd, bind with micromolar binding
      affinities to a number of tRNAs and form ternary complexes with tRNA(Pro) and
      prolyl-tRNA synthetase (ProRS). Fluorescence spectroscopy experiments also
      suggest that binding of HmdII and ProRS involves distinct binding determinants on
      the tRNA. These biochemical data suggest the possibility of a regulatory link
      between energy production and protein translation pathways that may allow a rapid
      cellular response to altered environmental conditions.

PMID- 22401294
TI  - Antitumor activities of ATP-competitive inhibitors of mTOR in colon cancer cells.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) is frequently activated in
      colon cancers due to mutations in the phosphatidylinositol 3-kinase (PI3K)
      pathway. Targeting mTOR with allosteric inhibitors of mTOR such as rapamycin
      reduces colon cancer progression in several experimental models. Recently, a new
      class of mTOR inhibitors that act as ATP-competitive inhibitors of mTOR, has been
      developed. The effectiveness of these drugs in colon cancer cells has however not
      been fully characterized. METHODS: LS174T, SW480 and DLD-1 colon cancer cell
      lines were treated with PP242 an ATP-competitive inhibitor of mTOR, NVP-BEZ235, a
      dual PI3K/mTOR inhibitor or rapamycin. Tumor cell growth, proliferation and
      survival were assessed by MTS assay, 5-bromo-2'-deoxyuridine (BrDU) incorporation
      or by quantification of DNA fragmentation respectively. In vivo, the anticancer
      activity of mTOR inhibitors was evaluated on nude mice bearing colon cancer
      xenografts. RESULTS: PP242 and NVP-BEZ235 reduced the growth, proliferation and
      survival of LS174T and DLD-1 colon cancer cells more efficiently than rapamycin.
      Similarly, PP242 and NVP-BEZ235 also decreased significantly the proliferation
      and survival of SW480 cells which were resistant to the effects of rapamycin. In
      vivo, PP242 and NVP-BEZ235 reduced the growth of xenografts generated from LS174T
      and SW480 cells. Finally, we also observed that the efficacy of ATP-competitive
      inhibitors of mTOR was enhanced by U0126, a MEK inhibitor. CONCLUSIONS: Taken
      together, these results show that ATP-competitive inhibitors of mTOR are
      effective in blocking colon cancer cell growth in vitro and in vivo and thus
      represent a therapeutic option in colon cancer either alone or in combination
      with MEK inhibitors.

PMID- 22401295
TI  - Age-related differences in daily physical activity divided by bout duration:
      preliminary findings in female convenience samples.
AB  - The purpose of the present investigation was to clarify the relationship between
      age and bout duration of physical activity (PA) under free-living conditions in
      female adults. Forty-three females wore an accelerometer (Lifecorder) for seven
      consecutive days in order to determine the time spent in PA at light intensity
      (LPA), at moderate intensity (MPA), and at vigorous intensity (VPA). The PA was
      divided according to the bout duration, such as PA lasting longer than 16 s, 32
      s, 60 s, 3 min, >5 min, and >10 min (PA16s, PA32s, PA1m, PA3m, PA5m, PA10m). The
      time for LPA32s, LPA1m, MPA16s, VPA16s, and the total time for MPA and VPA were
      significantly associated with age (P < 0.05). There were no significant
      associations between age and PA lasting >60 s, regardless of intensity category.
      The results of the present pilot study suggest that the age-associated
      differences in PA occur mainly in PA lasting 1 min or shorter duration.

PMID- 22401296
TI  - Measures of rowing performance.
AB  - Accurate measures of performance are important for assessing competitive athletes
      in practi~al and research settings. We present here a review of rowing
      performance measures, focusing on the errors in these measures and the
      implications for testing rowers. The yardstick for assessing error in a
      performance measure is the random variation (typical or standard error of
      measurement) in an elite athlete's competitive performance from race to race:
      ~1.0% for time in 2000 m rowing events. There has been little research interest
      in on-water time trials for assessing rowing performance, owing to logistic
      difficulties and environmental perturbations in performance time with such tests.
      Mobile ergometry via instrumented oars or rowlocks should reduce these problems,
      but the associated errors have not yet been reported. Measurement of boat speed
      to monitor on-water training performance is common; one device based on global
      positioning system (GPS) technology contributes negligible extra random error
      (0.2%) in speed measured over 2000 m, but extra error is substantial (1-10%) with
      other GPS devices or with an impeller, especially over shorter distances. The
      problems with on-water testing have led to widespread use of the Concept II
      rowing ergometer. The standard error of the estimate of on-water 2000 m time
      predicted by 2000 m ergometer performance was 2.6% and 7.2% in two studies,
      reflecting different effects of skill, body mass and environment in on-water
      versus ergometer performance. However, well trained rowers have a typical error
      in performance time of only ~0.5% between repeated 2000 m time trials on this
      ergometer, so such trials are suitable for tracking changes in physiological
      performance and factors affecting it. Many researchers have used the 2000 m
      ergometer performance time as a criterion to identify other predictors of rowing
      performance. Standard errors of the estimate vary widely between studies even for
      the same predictor, but the lowest errors (~1-2%) have been observed for peak
      power output in an incremental test, some measures of lactate threshold and
      measures of 30-second all-out power. Some of these measures also have typical
      error between repeated tests suitably low for tracking changes. Combining
      measures via multiple linear regression needs further investigation. In summary,
      measurement of boat speed, especially with a good GPS device, has adequate
      precision for monitoring training performance, but adjustment for environmental
      effects needs to be investigated. Time trials on the Concept II ergometer provide
      accurate estimates of a rower's physiological ability to output power, and some
      submaximal and brief maximal ergometer performance measures can be used
      frequently to monitor changes in this ability. On-water performance measured via
      instrumented skiffs that determine individual power output may eventually surpass
      measures derived from the Concept II.

PMID- 22401297
TI  - Reliability characteristics and conduction mechanisms in resistive switching
      memory devices using ZnO thin films.
AB  - In this work, bipolar resistive switching characteristics were demonstrated in
      the Pt/ZnO/Pt structure. Reliability tests show that ac cycling endurance level
      above 106 can be achieved. However, significant window closure takes place after
      about 102 dc cycles. Data retention characteristic exhibits no observed
      degradation after 168 h. Read durability shows stable resistance states after 106
      read times. The current transportation in ZnO films is dominated by the hopping
      conduction and the ohmic conduction in high-resistance and low-resistance states,
      respectively. Therefore, the electrical parameters of trap energy level, trap
      spacing, Fermi level, electron mobility, and effective density of states in
      conduction band in ZnO were identified.

PMID- 22401299
TI  - Bio serves nano: biological light-harvesting complex as energy donor for
      semiconductor quantum dots.
AB  - Light-harvesting complex (LHCII) of the photosynthetic apparatus in plants is
      attached to type-II core-shell CdTe/CdSe/ZnS nanocrystals (quantum dots, QD)
      exhibiting an absorption band at 710 nm and carrying a dihydrolipoic acid coating
      for water solubility. LHCII stays functional upon binding to the QD surface and
      enhances the light utilization of the QDs significantly, similar to its light
      harvesting function in photosynthesis. Electronic excitation energy transfer of
      about 50% efficiency is shown by donor (LHCII) fluorescence quenching as well as
      sensitized acceptor (QD) emission and corroborated by time-resolved fluorescence
      measurements. The energy transfer efficiency is commensurable with the expected
      efficiency calculated according to Forster theory on the basis of the estimated
      donor-acceptor separation. Light harvesting is particularly efficient in the red
      spectral domain where QD absorption is relatively low. Excitation over the entire
      visible spectrum is further improved by complementing the biological pigments in
      LHCII with a dye attached to the apoprotein; the dye has been chosen to absorb in
      the "green gap" of the LHCII absorption spectrum and transfers its excitation
      energy ultimately to QD. This is the first report of a biological light
      harvesting complex serving an inorganic semiconductor nanocrystal. Due to the
      charge separation between the core and the shell in type-II QDs the presented
      LHCII-QD hybrid complexes are potentially interesting for sensitized charge
      transfer and photovoltaic applications.

PMID- 22401300
TI  - Urut Melayu, the traditional Malay massage, as a complementary rehabilitative
      care in postpartum stroke.
AB  - BACKGROUND: The case of a 32-year-old Malay woman who developed postpartum stroke
      is reported. METHODS: The patient received a series of urut Melayu, the
      traditional Malay massage, sessions at one of the newly established integrated
      hospitals in the country. RESULTS: After 14 urut Melayu sessions, she improved
      tremendously in her speech and fine motor skills and regained her activities of
      daily living. CONCLUSIONS: This use of urut Melayu to complement rehabilitation
      care in patients poststroke is promising.

PMID- 22401298
TI  - Long-term neuropsychological, neuroanatomical, and life outcome in hippocampal
      amnesia.
AB  - Focal bilateral hippocampal damage typically causes severe and selective amnesia
      for new declarative information (facts and events), a cognitive deficit that
      greatly impacts the ability to live a normal, fully independent life. We describe
      the case of 1846, a 48-year-old woman with profound hippocampal amnesia following
      status epilepticus and an associated anoxic episode at age 30. Patient 1846 has
      undergone extensive neuropsychological testing on many occasions over the 18
      years since her injury, and we present data indicating that her memory impairment
      has remained severe and stable during that time. New, high-resolution, structural
      MRI studies of 1846's brain reveal substantial bilateral hippocampal atrophy
      resembling that of other well-known amnesic patients. In spite of severe amnesia
      1846 lives a full and mostly independent adult life, facilitated by an extensive
      social support network of family and friends. Her case provides an example of a
      rare and unlikely positive outcome in the face of severe memory problems.

PMID- 22401301
TI  - Basis set convergence of indirect spin-spin coupling constants in the Kohn-Sham
      limit for several small molecules.
AB  - The performance of more than 40 density functionals in predicting indirect spin
      spin coupling constants (SSCCs) in the Kohn-Sham basis set limit was tested. For
      comparison, similar calculations were performed using the RHF, SOPPA, SOPPA(CC2),
      and SOPPA(CCSD) methods, and the results were estimated toward the complete basis
      set (CBS) limit. The SSCCs of nine small molecules (N(2), CO, CO(2), NH(3),
      CH(4), C(2)H(2), C(2)H(4), C(2)H(6), and C(6)H(6)) were calculated using the
      dedicated Jensen pcJ-n polarization-consistent basis sets and used for the CBS
      limit estimations within the Kohn-Sham limit. These CBS results were compared
      with calculations using the aug-cc-pVTZ-J basis set. Among the 41 studied DFT
      methods, the tHCTHhyb, HSEh1PBE, HSE2PBE, wB97XD, wB97, and wB97X functionals
      reproduced accurately the experimental (1)J(XH) SSCCs and (3)J(HH60) and
      (2)J(HH(gem)) in ethane. Similarly, the functionals HSEh1PBE, HSE2PBE, wB97XD,
      wB97, and wB97X predicted accurately (1)J(CC), and B98, B97-1, B97-2, PBE1PBE,
      B1LYP, and O3LYP provided accurate (1)J(CO) results in the CO molecule. A very
      good performance for the calculation of the SSCCs based on the use of the
      relatively small basis set aug-cc-pVTZ-J was observed.

PMID- 22401302
TI  - Statistical analysis of survival data from radiation countermeasure experiments.
AB  - We present an introduction to, and examples of, Cox proportional hazards
      regression in the context of animal lethality studies of potential
      radioprotective agents. This established method is seldom used to analyze
      survival data collected in such studies, but is appropriate in many instances.
      Presenting a hypothetical radiation study that examines the efficacy of a
      potential radioprotectant both in the absence and presence of a potential
      modifier, we detail how to implement and interpret results from a Cox
      proportional hazards regression analysis used to analyze the survival data, and
      we provide relevant SAS(r) code. Cox proportional hazards regression analysis of
      survival data from lethal radiation experiments (1) considers the whole
      distribution of survival times rather than simply the commonly used proportions
      of animals that survived, (2) provides a unified analysis when multiple factors
      are present, and (3) can increase statistical power by combining information
      across different levels of a factor. Cox proportional hazards regression should
      be considered as a potential statistical method in the toolbox of radiation
      researchers.

PMID- 22401303
TI  - Magnetic resonance spectroscopy of cancer metabolism and response to therapy.
AB  - Magnetic resonance spectroscopy allows noninvasive in vivo measurements of
      biochemical information from living systems, ranging from cultured cells through
      experimental animals to humans. Studies of biopsies or extracts offer deeper
      insights by detecting more metabolites and resolving metabolites that cannot be
      distinguished in vivo. The pharmacokinetics of certain drugs, especially
      fluorinated drugs, can be directly measured in vivo. This review briefly
      describes these methods and their applications to cancer metabolism, including
      glycolysis, hypoxia, bioenergetics, tumor pH, and tumor responses to radiotherapy
      and chemotherapy.

PMID- 22401305
TI  - Selectivity, directionality, and promiscuity in peptide processing from a
      Bacillus sp. Al Hakam cyclodehydratase.
AB  - The thiazole/oxazole-modified microcins (TOMMs) represent a burgeoning class of
      ribosomal natural products decorated with thiazoles and (methyl)oxazoles
      originating from cysteines, serines, and threonines. The ribosomal nature of
      TOMMs allows for the generation of derivative products from mutations in the
      amino acid sequence of the precursor peptide, which ultimately manifest in
      differing structures and, sometimes, biological functions. Employing a TOMM
      system for the purpose of creating new structures and functions via combinatorial
      biosynthesis requires processing machinery that can tolerate highly variable
      substrates. In this study, TOMM enzymatic promiscuity was assessed using a
      currently uncharacterized cluster in Bacillus sp. Al Hakam. As determined by
      Fourier transform tandem mass spectrometry (FT-MS/MS), azole rings were formed in
      both a regio- and chemoselective fashion. Cognate and noncognate precursor
      peptides were modified in an overall C- to N-terminal directionality, which to
      date is unique among characterized ribosomal natural products. Studies focused on
      the inherent promiscuity of the biosynthetic machinery elucidated a modest bias
      for glycine at the preceding (-1) position and a remarkable flexibility in the
      following (+1) position, even allowing for the incorporation of charged amino
      acids and bisheterocyclization. Two unnatural substrates were utilized as the
      conclusive test of substrate flexibility, of which both were processed in a
      predictable fashion. A greater understanding of substrate processing and
      enzymatic tolerance toward unnatural substrates will prove beneficial when
      designing combinatorial libraries to screen for artificial TOMMs that exhibit
      desired activities.

PMID- 22401306
TI  - "Malignant" mitral stenosis.
AB  - Symptomatic mitral stenosis caused by a left atrial mass as the first sign of
      metastasis of a malignant tumor is extremely rare and frequently associated with
      poor prognosis. We report a case of a 59-year-old man with a history of grade 3
      malignant fibrous histiocytoma on his left tigh treated by limb-sparing surgery
      17 months earlier, who was admitted with 10-days of worsening dyspnea. Imaging
      revealed a left atrial mass protruding through the mitral valve that resulted in
      severe mitral stenosis. Biopsy confirmed metastasis of malignant fibrous
      histiocytoma.

PMID- 22401307
TI  - Subsecond absolute quantitation of amine metabolites using isobaric tags for
      discovery of pathway activation in mammalian cells.
AB  - The absolute quantitation of amine metabolites from mammalian cell samples was
      achieved by combining amine standards, isobaric tags, and capillary liquid
      chromatography (LC) tandem mass spectrometry (MS/MS). Our approach allowed 32
      specific amines to be analyzed within a single chromatographic run, with the
      generation of the calibration curve and absolute quantitation of each analyte
      taking less than 900 ms. Using this strategy, we determined the amine response of
      human aortic endothelial cells (HAECs) from a glucose challenge. The observed
      changes of the absolute concentration of these metabolites implied eight
      enzymatic reactions may change efficiency upon glucose treatment. Five of these
      reactions have been previously reported as being up-regulated in diabetic
      conditions. The remaining three reactions were analyzed by measuring the
      expression of these enzymes, with 66% showing increases. Our data indicate that
      rapid determination of absolute quantitation is useful in determining novel
      pathway activation. Furthermore, even though we determined the absolute quantity
      of 32 metabolites here, the number of analytes that can be measured by this
      method is limited mainly by commercial availability of amine standards.

PMID- 22401308
TI  - Intranasal vaccination with AAV5 and 9 vectors against human papillomavirus type
      16 in rhesus macaques.
AB  - Cervical cancer is the second most common cancer in women worldwide. Persistent
      high-risk human papillomavirus (HPV) infection has been identified as the
      causative event for the development of this type of cancer. Recombinant adeno
      associated viruses (rAAVs) are currently being developed and evaluated as vaccine
      vector. In previous work, we demonstrated that rAAVs administered intranasally in
      mice induced high titers and long-lasting neutralizing antibodies against HPV
      type 16 (HPV16). To extend this approach to a more human-related species, we
      immunized rhesus macaques (Macaca mulatta) with AAVs expressing an HPV16 L1
      protein using rAAV5 and 9 vectors in an intranasal prophylactic setting. An rAAV5
      L1 vector followed by a boost with rAAV9-L1 induced higher titers of L1-specific
      serum antibodies than a single rAAV5-L1 immunization. L1-specific antibodies
      elicited by AAV9 vector neutralized HPV16 pseudovirions and persisted for at
      least 7 months post immunization. Interestingly, nasal application of rAAV9 was
      immunogenic even in the presence of high AAV9 antibody titers, allowing
      reimmunization with the same serotype without prevention of the transgene
      expression. Two of six animals did not respond to AAV-mediated intranasal
      vaccination, although they were not tolerant, as both developed antibodies after
      intramuscular vaccination with HPV16 virus-like particles. These data clearly
      show the efficacy of an intranasal immunization using rAAV9-L1 vectors without
      the need of an adjuvant. We conclude from our results that rAAV9 vector is a
      promising candidate for a noninvasive nasal vaccination strategy.

PMID- 22401309
TI  - Declines in mental illness over the adult years: an enduring finding or
      methodological artifact?
AB  - OBJECTIVES: Epidemiological surveys have revealed dramatic declines in the
      prevalence of serious mental illness (SMI) as adults age. Analyses of these
      datasets have not determined whether this is attributable, on one hand, to
      declining incidence, shorter duration of condition, and lesser severity with age,
      or on the other hand, confounding variables and methodological biases. This
      study, thus, aims to test several such competing hypotheses. METHODS: This study
      employs a secondary analysis of data from the 2001/2002 US National Comorbidity
      Replication Survey of 9282 adults, 18 and older, living in the household
      population of the 48 contiguous states, as well as supplemental datasets from
      Israel, New Zealand, and other sources. RESULTS: One-year SMI prevalence rates in
      the US drop from 8.0% of adults 18-29 to 1.4% of the 65+, and to similar degrees
      in Israel and New Zealand. The drop in the US can be explained by the early onset
      of most mental illnesses, and declines in both incidence and duration of
      condition with age. Comorbidity also drops with age; however, the remaining
      diagnoses show a gradually increasing severity. Institutionalization explains a
      small portion of the declines, as does premature mortality of the seriously
      mentally ill that accounts for 16.3% of the decline. CONCLUSION: The results
      reveal that a substantial portion of the declines are explainable in terms of
      declining incidence and improving recovery rates, with some reduction also
      attributable to institutionalization and premature mortality which removes some
      older and more seriously disabled adults from the epidemiological survey
      populations.

PMID- 22401311
TI  - Relationships between deprivation and duration of children's emergency admissions
      for breathing difficulty, feverish illness and diarrhoea in North West England:
      an analysis of hospital episode statistics.
AB  - BACKGROUND: In the United Kingdom there has been a long term pattern of increases
      in children's emergency admissions and a substantial increase in short stay
      unplanned admissions. The emergency admission rate (EAR) per thousand population
      for breathing difficulty, feverish illness and diarrhoea varies substantially
      between children living in different Primary Care Trusts (PCTs). However, there
      has been no examination of whether disadvantage is associated with short stay
      unplanned admissions at PCT-level. The aim of this study was to determine whether
      differences between emergency hospital admission rates for breathing difficulty,
      feverish illness and diarrhoea are associated with population-level measures of
      multiple deprivation and child well-being, and whether there is variation by
      length of stay and age. METHODS: Analysis of hospital episode statistics and
      secondary analysis of Index of Multiple Deprivation (IMD) 2007 and Local Index of
      Child Well-being (CWI) 2009 in ten adjacent PCTs in North West England. The
      outcome measure for each PCT was the emergency admission rate to hospital for
      breathing difficulty, feverish illness and diarrhoea. RESULTS: 23,496 children
      aged 0-14 were discharged following emergency admission for breathing difficulty,
      feverish illness and/or diarrhoea during 2006/07. The emergency admission rate
      ranged from 27.9 to 62.7 per thousand. There were no statistically significant
      relationships between shorter (0 to 3 day) hospitalisations and the IMD or
      domains of the CWI. The rate for hospitalisations of 4 or more days was
      associated with the IMD (Kendall's tau(b) = 0.64) and domains of the CWI:
      Environment (tau(b) = 0.60); Crime (tau(b) = 0.56); Material (tau(b) = 0.51);
      Education (tau(b) = 0.51); and Children in Need (tau(b) = 0.51). This pattern was
      also evident in children aged under 1 year, who had the highest emergency
      admission rates. There were wide variations between the proportions of children
      discharged on the day of admission at different hospitals. CONCLUSIONS:
      Differences between rates of the more common shorter (0 to 3 day)
      hospitalisations were not explained by deprivation or well-being measured at PCT
      level. Indices of multiple deprivation and child well-being were only associated
      with rates of children's emergency admission for breathing difficulty, feverish
      illness and diarrhoea for hospitalisations of 4 or more days.

PMID- 22401310
TI  - Identification of an ubinuclein 1 region required for stability and function of
      the human HIRA/UBN1/CABIN1/ASF1a histone H3.3 chaperone complex.
AB  - The mammalian HIRA/UBN1/CABIN1/ASF1a (HUCA) histone chaperone complex deposits
      the histone H3 variant H3.3 into chromatin and is linked to gene activation,
      repression, and chromatin assembly in diverse cell contexts. We recently reported
      that a short N-terminal fragment of UBN1 containing amino acids 1-175 is
      necessary and sufficient for interaction with the WD repeats of HIRA and
      attributed this interaction to a region from residues 120-175 that is highly
      conserved with the yeast ortholog Hpc2 and so termed the HRD for Hpc2-related
      domain. In this report, through a more comprehensive and refined biochemical and
      mutational analysis, we identify a smaller and more moderately conserved region
      within residues 41-77 of UBN1, which we term the NHRD, that is essential for
      interaction with the HIRA WD repeats; we further demonstrate that the HRD is
      dispensable for this interaction. We employ analytical ultracentrifugation
      studies to demonstrate that the NHRD of UBN1 and the WD repeats of HIRA form a
      tight 1:1 complex with a dissociation constant in the nanomolar range.
      Mutagenesis experiments identify several key residues in the NHRD that are
      required for interaction with the HIRA WD repeat domain, stability of the HUCA
      complex in vitro and in vivo, and changes in chromatin organization in primary
      human cells. Together, these studies implicate the NHRD domain of UBN1 as being
      an essential region for HIRA interaction and chromatin organization by the HUCA
      complex.

PMID- 22401312
TI  - The effect of education in hospice and palliative care on emergency medicine
      residents' knowledge and referral patterns.
AB  - OBJECTIVES: To determine: (1) residents' knowledge base in key concepts in
      hospice and palliative care, (2) residents' comfort level in discussing end-of
      life (EOL) care and managing EOL symptoms, and (3) if a brief educational
      intervention improves residents' knowledge of and comfort in dealing with EOL
      issues both immediately following and six months after the intervention. METHODS:
      This prospective cohort study was performed at a level-1 community trauma center.
      A survey was developed regarding knowledge of palliative care and its emergency
      department (ED) utilization and administered to emergency medicine (EM)
      residents. Subsequently, residents underwent four hours of palliative care
      training. An identical post-education survey was administered immediately and
      then six months later. RESULTS: Education improved knowledge of hospice
      qualifying diagnoses which was maintained at six months. Improvement in
      residents' ability to convert between oral and intravenous formulations of
      opioids was not retained at six months. Education was not shown to improve EM
      residents' comfort in managing pain or dyspnea but it was shown to improve their
      comfort level in discussing EOL care with patients and families Inpatient hospice
      admissions from the ED increased 88% after the education. Identified barriers to
      providing palliative care in the ED decreased. CONCLUSIONS: There are gaps in EM
      residents' hospice and palliative care knowledge. Education is shown to improve
      and maintain knowledge of hospice qualifying diagnoses, comfort level in
      discussing EOL care with patients and families, and to increase inpatient hospice
      admissions from the ED.

PMID- 22401313
TI  - Continuous intravenous infusion of ketamine and lidocaine as adjuvant analgesics
      in a 5-year-old patient with neuropathic cancer pain.
AB  - For difficult to treat neuropathic pain from cancer, adjuvant analgesics are
      often used with opioids. We present the case of a 5-year-old girl who was
      diagnosed with meningitis caused by malignant T-cell lymphoma. She had severe
      neuropathic pain not relieved by increasing doses of a fentanyl infusion.
      Intravenous administration of ketamine and lidocaine in combination with fentanyl
      provided excellent analgesia without significant side effects. Ketamine and
      lidocaine can be safely infused together with concomitant opioids for the
      treatment of refractory neuropathic pain caused by cancer.

PMID- 22401314
TI  - Needs, experiences, and preferences of sexual minorities for end-of-life care and
      palliative care: a systematic review.
AB  - OBJECTIVES: To identify and appraise the existing evidence for the needs,
      experiences, and preferences for palliative and end-of-life (EOL) care in
      lesbian, gay, bisexual and transgender (LGBT) populations. METHOD: The databases
      searched were Medline (1950-present), PsycInfo (1806-2010), Cinahl (1982-2010),
      and ASSIA (1987-2010). RESULTS: Among 4483 articles, 133 papers were chosen for
      further exploration. Overall, 12 papers were retained in the study. The majority
      of papers focused on the cancer experience of gay men and lesbian women. Only a
      few papers had evidence for the bisexual population, while no studies related to
      transgender people. CONCLUSIONS: Existing evidence is explicit and indeed
      repetitive in highlighting the educational needs of health care professionals to
      explore sexual preferences, avoid heterosexist assumptions, and recognize the
      importance of partners in decision making. There is also a significant need to
      research LGBT experiences and refine services for patients and their caregivers.

PMID- 22401315
TI  - Carvedilol or propranolol in portal hypertension? A randomized comparison.
AB  - OBJECTIVES: Carvedilol is a non-selective beta-blocker with intrinsic anti
      alpha(1)-adrenergic activity, potentially more effective than propranolol in
      reducing hepatic venous pressure gradient (HVPG). We compared the long-term
      effect of carvedilol and propranolol on HVPG and assessed whether the acute
      response to oral propranolol predicted the long-term HVPG response on either
      drug. MATERIAL AND METHODS: HVPG was measured in 38 patients with cirrhosis and
      HVPG >= 12 mm Hg at baseline and then again 90 min after an oral dose of 80 mg
      propranolol. Patients were double-blinded randomized to either carvedilol (21
      patients) or propranolol (17 patients) and after 90 days of treatment HVPG
      measurements were repeated. RESULTS: HVPG decreased by 19.3 +/- 16.1% (p < 0.01)
      and by 12.5 +/- 16.7% (p < 0.01) in the carvedilol and propranolol groups,
      respectively, with no significant difference between treatment regimens (p =
      0.21). Although insignificant, an acute decrease in HVPG of >=12% was the best
      cut-off value to predict long-term HVPG response to propranolol when using ROC
      curve analysis. CONCLUSIONS: This randomized study showed that carvedilol is at
      least as effective as propranolol on HVPG after long-term administration.
      Furthermore, a predictive value of an acute propranolol test on HVPG could not be
      confirmed.

PMID- 22401316
TI  - The need for clinical accuracy guidelines for blood glucose monitors.

PMID- 22401317
TI  - Association of hyperglycemia, glucocorticoids, and insulin use with morbidity and
      mortality in the pediatric intensive care unit.
AB  - BACKGROUND: Studies of pediatric intensive care unit (PICU) patients have shown a
      significant association of morbidity and mortality with hyperglycemia. We
      retrospectively evaluated the degree of hyperglycemia as well as its correlation
      with glucocorticoid and insulin use and assessed its association with hospital
      length of stay (LOS) and mortality. This study preceded the initiation of a
      standard glycemic control protocol. METHODS: We examined medical records at
      Kosair Children's Hospital for all PICU admissions from 2008 of patients without
      diabetes mellitus. Critical illness hyperglycemia (CIH) was defined by having
      three or more peak glucose values greater than thresholds of 110, 140, 180, and
      200 mg/dl. These patients were evaluated for glucocorticoid, insulin use, and
      outcome measures. RESULTS: We evaluated the eligible 1173 admissions, where 10.5%
      of these patients reached the highest threshold (200 mg/dl) of CIH.
      Glucocorticoids were used in 43% of these patients, with dexamethasone being the
      most common (58%). There was a significant correlation between glucocorticoids
      and higher peak glucose values, where 81% of the patients who were above the 200
      mg/dl cutoff level were treated with glucocorticoids. Only 36.8% in that group
      were also treated with insulin. Patients at the 200 mg/dl cutoff had the highest
      median PICU and total hospital length of stays (4 and 10 days, respectfully).
      Mortality was associated with increasing glucose levels, reaching 18.7% among
      patients above the 200 mg/dl cutoff. CONCLUSION: Hyperglycemia was prevalent in
      the PICU and was associated with increased morbidity, as characterized by
      increased LOS and increased mortality. Glucocorticoid use was prevalent among
      patients exhibiting hyperglycemia. Insulin use was uncommon.

PMID- 22401318
TI  - Glycemic control in the pediatric intensive care unit of Leuven: two years of
      experience.
AB  - Stress hyperglycemia and hypoglycemia are associated with increased mortality and
      morbidity in critically ill patients. Three randomized controlled trials, in the
      surgical, medical, and pediatric intensive care unit (PICU) of the Leuven
      University in Belgium, demonstrated the beneficial response of tightly
      controlling blood glucose levels within age-adjusted narrow limits by applying
      intensive insulin therapy. Follow-up studies could not confirm the results
      obtained in the Leuven studies but revealed the complexity associated with tight
      glycemic control (TGC). This article gives an overview of the methodological
      aspects typical of the Leuven TGC concept, with the focus on the PICU.
      Differences between the adult and the PICU are described. This overview article
      might help other ICUs by addressing potential differences in clinical practice
      when implementing TGC.

PMID- 22401319
TI  - Blood glucose measurements in critically ill patients.
AB  - Studies on tight glycemic control by intensive insulin therapy abruptly changed
      the climate of limited interest in the problem of hyperglycemia in critically ill
      patients and reopened the discussion on accuracy and reliability of glucose
      sensor devices. This article describes important components of blood glucose
      measurements and their interferences with the focus on the intensive care unit
      setting. Typical methodologies, organized from analytical accuracy to clinical
      accuracy, to assess imprecision and bias of a glucose sensor are also discussed.
      Finally, a list of recommendations and requirements to be considered when
      evaluating (time-discrete) glucose sensor devices is given.

PMID- 22401320
TI  - Critical illness hyperglycemia in pediatric cardiac surgery.
AB  - Critical illness hyperglycemia (CIH) is common in pediatric and adult intensive
      care units (ICUs). Children undergoing surgical repair or palliation of
      congenital cardiac defects are particularly at risk for CIH and its occurrence
      has been associated with increased morbidity and mortality in this population.
      Strict glycemic control through the use of intensive insulin therapy (IIT) has
      been shown to improve outcomes in some adult and pediatric studies, yet these
      findings have sparked controversy. The practice of strict glycemic control has
      been slow in extending to pediatric ICUs because of the documented increase in
      the incidence of hypoglycemia in patients treated with IIT. Protocol driven
      approaches with more liberal glycemic targets have been successfully validated in
      general and cardiac critical care pediatric patients with low rates of
      hypoglycemia. It is unknown whether a therapeutic benefit is obtained by keeping
      patients in this more liberal glycemic control target. Definitive randomized
      controlled trials of IIT utilizing these targets in critically ill children are
      ongoing.

PMID- 22401321
TI  - Stress hyperglycemia in pediatric critical illness: the intensive care unit adds
      to the stress!
AB  - Stress hyperglycemia (SH) commonly occurs during critical illness in children.
      The historical view that SH is beneficial has been questioned in light of
      evidence that demonstrates the association of SH with worse outcomes. In addition
      to intrinsic changes in glucose metabolism and development of insulin resistance,
      specific intensive care unit (ICU) practices may influence the development of SH
      during critical illness. Mechanical ventilation, vasoactive infusions, renal
      replacement therapies, cardiopulmonary bypass and extracorporeal life support,
      therapeutic hypothermia, prolonged immobility, nutrition support practices, and
      the use of medications are all known to mediate development of SH in critical
      illness. Tight glucose control (TGC) to manage SH has emerged as a promising
      therapy to improve outcomes in critically ill adults, but results have been
      inconclusive. Large variations in ICU practices across studies likely resulted in
      inconsistent results. Future studies of TGC need to take into account the impact
      of commonly used ICU practices and, ideally, standardize protocols in an attempt
      to improve the accuracy of conclusions from such studies.

PMID- 22401322
TI  - Hypoglycemia in critically ill children.
AB  - BACKGROUND: The practice of glycemic control with intravenous insulin in
      critically ill patients has brought clinical focus on understanding the effects
      of hypoglycemia, especially in children. Very little is published on the impact
      of hypoglycemia in this population. We aimed to review the existing literature on
      hypoglycemia in critically ill neonates and children. METHODS: We performed a
      systematic review of the literature up to August 2011 using PubMed, Ovid MEDLINE
      and ISI Web of Science using the search terms "hypoglycemia or hypoglyc*" and
      "critical care or intensive care or critical illness". Articles were limited to
      "all child (0-18 years old)" and "English". RESULTS: A total of 513 articles were
      identified and 132 were included for review. Hypoglycemia is a significant
      concern among pediatric and neonatal intensivists. Its definition is complicated
      by the use of a biochemical measure (i.e., blood glucose) for a pathophysiologic
      problem (i.e., neuroglycopenia). Based on associated outcomes, we suggest
      defining hypoglycemia as <40-45 mg/dl in neonates and <60-65 mg/dl in children.
      Below the suggested threshold values, hypoglycemia is associated with worse
      neurological outcomes, increased intensive care unit stay, and increased
      mortality. Disruptions in carbohydrate metabolism increase the risk of
      hypoglycemia incritically ill children. Prevention of hypoglycemia, especially in
      the setting of intravenous insulin use, will be best accomplished by the
      combination of accurate measuring techniques, frequent or continuous glucose
      monitoring, and computerized insulin titration protocols. CONCLUSION: Studies on
      hypoglycemia in critically ill children have focused on spontaneous hypoglycemia.
      With the current practice of maintaining blood glucose within a narrow range with
      intravenous insulin, the risk factors and outcomes associated with insulin
      induced hypoglycemia should be rigorously studied to prevent hypoglycemia and
      potentially improve outcomes of critically ill children.

PMID- 22401323
TI  - "One more thing to think about..." Cognitive burden experienced by intensive care
      unit nurses when implementing a tight glucose control protocol.
AB  - Critically ill patients require intensive nursing care. Intensive care unit (ICU)
      nurses, who care for these physiologically unstable patients, are continuously
      occupied with the integration of assessments, monitoring, and interventions that
      are responsive to a patient's evolving state. Since 2005, numerous evidenced
      based clinical protocols have been implemented in the critical care unit.
      Individually, each may not appear to be burdensome but, collectively, these
      clinical protocols add to the cognitive work of ICU nurses. While nurses are
      central to the successful implementation of these protocols, little is written
      about the cognitive burden imposed on them by the addition of these clinical
      protocols. This article explores the impact of clinical protocols on the
      cognitive burden of ICU nurses, using a tight glucose control (TGC) protocol as
      an exemplar case. Research from management, ergonomics, systems engineering, and
      nursing is used to build the concept of cognitive burden. Future research can
      build upon this understanding to facilitate successful implementation of clinical
      protocols.

PMID- 22401324
TI  - Population-based study of severe hypoglycemia requiring emergency medical service
      assistance reveals unique findings.
AB  - OBJECTIVE: The objective is to report a contemporary population-based estimate of
      hypoglycemia requiring emergency medical services (EMS), its burden on medical
      resources, and its associated mortality in patients with or without diabetes
      mellitus (DM, non-DM), which will enable development of prospective strategies
      that will capture hypoglycemia promptly and provide an integrated approach for
      prevention of such episodes. METHODS: We retrieved all ambulance calls activated
      for hypoglycemia in Olmsted County, Minnesota, between January 1, 2003 and
      December 31, 2009. RESULTS: A total of 1473 calls were made by 914 people (DM 8%,
      non-DM 16%, unknown DM status 3%). Mean age was 60 +/- 16 years with 49% being
      female. A higher percentage of calls were made by DM patients (87%) with
      proportionally fewer calls coming from non-DM patients (11%) (chi-square test, p
      < .001), and the remaining 2% calls by people with unknown DM status. Emergency
      room transportation and hospitalization were significantly higher in non-DM
      patients compared to DM patients (p < .001) and type 2 diabetes mellitus compared
      to type 1 diabetes mellitus (p < .001). Sulphonylureas alone or in combination
      with insulin varied during the study period (p = .01). The change in incidence of
      EMS for hypoglycemia was tracked during this period. However, causality has not
      been established. Death occurred in 240 people, 1.2 (interquartile range 0.2-2.7)
      years after their first event. After adjusting for age, mortality was higher in
      non-DM patients compared with DM patients (p < .001) but was not different
      between the two types of DM. CONCLUSIONS: The population burden of EMS requiring
      hypoglycemia is high in both DM and non-DM patients, and imposes significant
      burden on medical resources. It is associated with long-term mortality.

PMID- 22401325
TI  - Paper electrocardiograph strips may contain overlooked clinical information in
      screen-detected type 2 diabetes patients.
AB  - BACKGROUND: A large number of nondigitized electrocardiograph (ECG) strips are
      routinely collected in larger cohort studies such as the ADDITION study (Anglo
      Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes
      in Primary Care). These ECG strips are routinely read manually but may contain
      overlooked information revealing cardiac autonomic dysfunction. The aim of this
      study was to investigate whether clinical information may be lost using manual R
      wave to R wave (RR) interval measurements in the calculation of heart rate
      variability (HRV) in patients with type 2 diabetes mellitus (T2DM). METHOD: From
      the Danish part of the ADDITION study, we randomly selected 120 T2DM patients at
      baseline of the ADDITION study. Analysis of the ECG strips was performed using
      two different methods: (1) by experienced technicians using rulers and (2) by
      experienced technicians using a high-resolution computer-assisted method.
      Calculation of heart rate and time domain HRV [standard deviation of normal-to
      normal RR intervals (SDNN) and root mean square of successive differences
      (RMSSD)] were performed with the same software. RESULTS: When comparing results
      from the two methods, the following values of Pearson's r are obtained: 0.98 for
      heart rate, 0.76 for SDNN, and 0.68 for RMSSD. These results indicate that heart
      rate and HRV measurements by the computer-assisted and manually based methods
      correlate. However, Bland-Altman plots and Pitman's test of difference in
      variance revealed poor agreements (p < .01) for both HRV measurements (SDNN and
      RMSSD); only heart rate showed substantiated agreement (p = .54) between the two
      methods. Low HRV was statistically significantly associated to high heart rate,
      systolic blood pressure, and diastolic blood pressure in these screen-detected
      T2DM patients. CONCLUSIONS: Paper ECG strips may contain overlooked clinical
      information on the status of autonomic function in patients with T2DM. In our
      study, manual measurements of RR intervals were inferior to the computer-assisted
      method. Based on this study, we recommend cautiousness in the clinical use and
      interpretation of HRV based on manual or low resolution measurements of RR
      intervals from ECG strips. High resolution measurements of RR intervals reveal
      significant associations between low HRV and high heart rate, systolic blood
      pressure, and diastolic blood pressure among patients with screen-detected T2DM.
      It is feasible to use a computer-assisted method to determine RR intervals in
      patients with T2DM.

PMID- 22401326
TI  - Effect of disinfectants on glucose monitors.
AB  - BACKGROUND: Monitoring blood glucose levels is an integral part of routine
      diabetes management. To minimize the risk of transmission of bloodborne pathogens
      during monitoring, the Centers for Disease Control and Prevention (CDC)
      recommends that glucose meters be disinfected after each use whenever they are
      used to test multiple patients. The objective of this study is to assess the
      compatibility of some common disinfectants with certain blood glucose meter
      systems. METHODS: We tested six disinfectants for adverse impact on meter
      performance or the exterior meter surfaces. The disinfectants tested were 0.525%
      sodium hypochlorite, 20% 2-propanol and 10% ethanol, 17.2% isopropanol, 55%
      isopropanol, 70% isopropanol, and hydrogen peroxide. To assess meter performance,
      we tested OneTouch(r) Ultra(r) blood glucose monitoring systems with control
      solution before and after application of either water or disinfectant. To assess
      the effect on exterior meter surfaces, we performed a soaking test to simulate
      long-term exposure to disinfectant. RESULTS: Paired t-test results showed that
      the control solution data associated with disinfectant and with water application
      were not significantly different for each meter type. However, most of the meter
      types were adversely affected by hydrogen peroxide and/or by the higher
      concentrations of alcohol-based disinfectants. CONCLUSIONS: Although none of the
      six disinfectants affected meter performance, hydrogen peroxide and isopropanol
      >20% adversely affected the exterior surfaces of the tested meters. When
      complying with CDC instructions for meter disinfection, users should use caution
      and choose disinfectants that have been validated by the meter manufacturer.

PMID- 22401327
TI  - Noninvasive measurement of plasma triglycerides and free fatty acids from exhaled
      breath.
AB  - BACKGROUND: Although altered metabolism has long been known to affect human
      breath, generating clinically usable metabolic tests from exhaled compounds has
      proven challenging. If developed, a breath-based lipid test would greatly
      simplify management of diabetes and serious pathological conditions (e.g.,
      obesity, familial hyperlipidemia, and coronary artery disease), in which systemic
      lipid levels are a critical risk factor for onset and development of future
      cardiovascular events. METHODS: We, therefore, induced controlled fluctuations of
      plasma lipids (insulin-induced lipid suppression or intravenous infusion of
      Intralipid) during 4-h in vivo experiments on 23 healthy volunteers (12 males/11
      females, 28.0 +/- 0.3 years) to find correlations between exhaled volatile
      organic compounds and plasma lipids. In each subject, plasma triglycerides (TG)
      and free fatty acids (FFA) concentrations were both directly measured and
      calculated via individualized prediction equations based on the multiple linear
      regression analysis of a cluster of 4 gases. In the lipid infusion protocol, we
      also generated common prediction equations using a maximum of 10 gases. RESULTS:
      This analysis yielded strong correlations between measured and predicted values
      during both lipid suppression (r = 0.97 for TG; r = 0.90 for FFA) and lipid
      infusion (r = 0.97 for TG; r = 0.94 for FFA) studies. In our most accurate common
      prediction model, measured and predicted TG and FFA values also displayed very
      strong statistical agreement (r = 0.86 and r = 0.81, respectively). CONCLUSIONS:
      Our results demonstrate the feasibility of measuring plasma lipids through breath
      analysis. Optimization of this technology may ultimately lead to the development
      of portable breath analyzers for plasma lipids, replacing blood-based bioassays.

PMID- 22401329
TI  - Primary care provider perceptions of the effectiveness of two self-management
      support programs for vulnerable patients with diabetes.
AB  - BACKGROUND: Primary care providers (PCPs) in safety net settings face barriers to
      optimizing care for patients with diabetes. We conducted this study to assess
      PCPs' perspectives on the effectiveness of two language-concordant diabetes self
      management support programs. METHODS: One year postintervention, we surveyed PCPs
      whose patients with diabetes participated in a three-arm multiclinic randomized
      controlled trial comparing usual care (UC), weekly automated telephone self
      management (ATSM) support with nurse care management, and monthly group medical
      visits (GMVs). We compared PCP perspectives on patient activation to create and
      achieve goals, quality of care, and barriers to care using regression models
      accounting for within-PCP clustering. RESULTS: Of 113 eligible PCPs caring for
      330 enrolled patients, 87 PCPs (77%) responded to surveys about 245 (74%)
      enrolled patients. Intervention patients were more likely to be perceived by PCPs
      as activated to create and achieve goals for chronic care when compared with UC
      patients (standardized effect size, ATSM vs UC, +0.41, p = 0.01; GMV vs UC,
      +0.31, p = 0.05). Primary care providers rated quality of care as higher for
      patients exposed to ATSM compared to UC (odds ratio 3.6, p < 0.01). Compared with
      GMV patients, ATSM patients were more likely to be perceived by PCPs as
      overcoming barriers related to limited English proficiency (82% ATSM vs 44% GMV,
      p = 0.01) and managing medications (80% ATSM vs 53% GMV, p = 0.01). CONCLUSIONS:
      Primary care providers perceived that patients receiving ATSM support had
      overcome barriers, participated more actively, and received higher quality
      diabetes care. These views of clinician stakeholders lend additional evidence for
      the potential to upscale ATSM more broadly to support PCPs in their care of
      diverse, multilinguistic populations.

PMID- 22401328
TI  - Stochastic targeted (STAR) glycemic control: design, safety, and performance.
AB  - INTRODUCTION: Tight glycemic control (TGC) has shown benefits but has been
      difficult to achieve consistently. STAR (Stochastic TARgeted) is a flexible,
      model-based TGC approach that directly accounts for intra- and interpatient
      variability with a stochastically derived maximum 5% risk of blood glucose (BG)
      below 72 mg/dl. This research assesses the safety, efficacy, and clinical burden
      of a STAR TGC controller modulating both insulin and nutrition inputs in virtual
      and clinical pilot trials. METHODS: Clinically validated virtual trials using
      data from 370 patients in the SPRINT (Specialized Relative Insulin and Nutrition
      Titration) study were used to design the STAR protocol and test its safety,
      performance, and required clinical effort prior to clinical pilot trials. Insulin
      and nutrition interventions were given every 1-3 h as chosen by the nurse to
      allow them to manage workload. Interventions were designed to maximize the
      overlap of the model-predicted (5-95(th) percentile) range of BG outcomes with
      the 72-117 mg/dl band and thus provide a maximum 5% risk of BG <72 mg/dl.
      Interventions were calculated using clinically validated computer models of human
      metabolism and its variability in critical illness. Carbohydrate intake (all
      sources) was selected to maximize intake up to 100% of the American College of
      Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) goal (25
      kg/kcal/h). Insulin doses were limited (8 U/h maximum), with limited increases
      based on current rate (0.5-2.0 U/h). Initial clinical pilot trials involved 3
      patients covering ~450 h. Approval was granted by the Upper South A Regional
      Ethics Committee. RESULTS: Virtual trials indicate that STAR provides similar
      glycemic control performance to SPRINT with 2-3 h (maximum) measurement
      intervals. Time in the 72-126 mg/dl and 72-145 mg/dl bands was equivalent for all
      controllers, indicating that glycemic outcome differences between protocols were
      only shifted in this range. Safety from hypoglycemia was improved. Importantly,
      STAR using 2-3 h (maximum) intervention intervals reduced clinical burden up to
      30%, which is clinically very significant. Initial clinical trials showed
      glycemic performance, safety, and management of inter- and intrapatient
      variability that matched or exceeded the virtual trial results. CONCLUSIONS: In
      virtual trials, STAR TGC provided tight control that maximized the likelihood of
      BG in a clinically specified glycemic band and reduced hypoglycemia with a
      maximum 5% (or lower) expected risk of light hypoglycemia (BG <72 mg/dl) via
      model-based management of intra- and interpatient variability. Clinical workload
      was self-managed and reduced up to 30% compared with SPRINT. Initial pilot
      clinical trials matched or exceeded these virtual results.

PMID- 22401330
TI  - Interface design and human factors considerations for model-based tight glycemic
      control in critical care.
AB  - INTRODUCTION: Tight glycemic control (TGC) has shown benefits but has been
      difficult to implement. Model-based methods and computerized protocols offer the
      opportunity to improve TGC quality and compliance. This research presents an
      interface design to maximize compliance, minimize real and perceived clinical
      effort, and minimize error based on simple human factors and end user input.
      METHOD: The graphical user interface (GUI) design is presented by construction
      based on a series of simple, short design criteria based on fundamental human
      factors engineering and includes the use of user feedback and focus groups
      comprising nursing staff at Christchurch Hospital. The overall design maximizes
      ease of use and minimizes (unnecessary) interaction and use. It is coupled to a
      protocol that allows nurse staff to select measurement intervals and thus self
      manage workload. RESULTS: The overall GUI design is presented and requires only
      one data entry point per intervention cycle. The design and main interface are
      heavily focused on the nurse end users who are the predominant users, while
      additional detailed and longitudinal data, which are of interest to doctors
      guiding overall patient care, are available via tabs. This dichotomy of needs and
      interests based on the end user's immediate focus and goals shows how interfaces
      must adapt to offer different information to multiple types of users.
      CONCLUSIONS: The interface is designed to minimize real and perceived clinical
      effort, and ongoing pilot trials have reported high levels of acceptance. The
      overall design principles, approach, and testing methods are based on fundamental
      human factors principles designed to reduce user effort and error and are readily
      generalizable.

PMID- 22401331
TI  - Data entry errors and design for model-based tight glycemic control in critical
      care.
AB  - INTRODUCTION: Tight glycemic control (TGC) has shown benefits but has been
      difficult to achieve consistently. Model-based methods and computerized protocols
      offer the opportunity to improve TGC quality but require human data entry,
      particularly of blood glucose (BG) values, which can be significantly prone to
      error. This study presents the design and optimization of data entry methods to
      minimize error for a computerized and model-based TGC method prior to pilot
      clinical trials. METHOD: To minimize data entry error, two tests were carried out
      to optimize a method with errors less than the 5%-plus reported in other studies.
      Four initial methods were tested on 40 subjects in random order, and the best two
      were tested more rigorously on 34 subjects. The tests measured entry speed and
      accuracy. Errors were reported as corrected and uncorrected errors, with the sum
      comprising a total error rate. The first set of tests used randomly selected
      values, while the second set used the same values for all subjects to allow
      comparisons across users and direct assessment of the magnitude of errors. These
      research tests were approved by the University of Canterbury Ethics Committee.
      RESULTS: The final data entry method tested reduced errors to less than 1-2%, a
      60-80% reduction from reported values. The magnitude of errors was clinically
      significant and was typically by 10.0 mmol/liter or an order of magnitude but
      only for extreme values of BG < 2.0 mmol/liter or BG > 15.0-20.0 mmol/liter, both
      of which could be easily corrected with automated checking of extreme values for
      safety. CONCLUSIONS: The data entry method selected significantly reduced data
      entry errors in the limited design tests presented, and is in use on a clinical
      pilot TGC study. The overall approach and testing methods are easily performed
      and generalizable to other applications and protocols.

PMID- 22401332
TI  - Use of an automated bolus calculator reduces fear of hypoglycemia and improves
      confidence in dosage accuracy in patients with type 1 diabetes mellitus treated
      with multiple daily insulin injections.
AB  - BACKGROUND: Many patients do not intensify their insulin regimens. It is believed
      that lack of adherence may be largely due to fear of hypoglycemia. We
      hypothesized that utilization of an automated bolus calculator (bolus advisor)
      might reduce fear of hypoglycemia and encourage patients to achieve improved
      glycemic control. METHOD: We surveyed 1,412 type 1 diabetes mellitus (T1DM)
      patients treated with multiple daily insulin injection therapy at 270 hospitals
      in the United Kingdom and Republic of Ireland to assess their attitudes and
      behaviors regarding insulin therapy after use of a bolus advisor (Accu-Chek(r)
      Aviva Expert blood glucose meter and bolus advisor system, Roche Diagnostics).
      The device automatically calculates bolus dosages based on current blood glucose
      values, anticipated meal intake, and other parameters. RESULTS: Five hundred
      eighty-eight T1DM patients responded to the survey. Respondents were
      predominantly female, age <1 to 70 years, with diabetes duration of <1 to >15
      years. Respondents had 4-12 weeks prior experience using the bolus advisor. 76.7%
      of respondents indicated current bolus advisor use to calculate insulin boluses
      for meals/snacks always or quite often. 52.0% of respondents indicated that fear
      of hypoglycemia was reduced (39.0%) or significantly reduced (13.0%). 78.8%
      indicated that confidence in the insulin dose calculation improved (50.8%) or
      significantly improved (28.0%). 89.3% indicated that the bolus advisor made bolus
      calculation easy or very easy compared with manual calculation. CONCLUSIONS: Most
      patients felt that using the bolus advisor was easier than manual bolus
      calculation, improved their confidence in the accuracy of their bolus dosage, and
      reduced their fear of hypoglycemia. Randomized trials are needed to confirm these
      perceptions and determine whether bolus advisor use improves clinical outcomes.

PMID- 22401333
TI  - Analysis of use of an automated bolus calculator reduces fear of hypoglycemia and
      improves confidence in dosage accuracy in type 1 diabetes mellitus patients
      treated with multiple daily insulin injections.
AB  - In this issue of Journal of Diabetes Science and Technology, Barnard and
      colleagues evaluate the use of the ACCU-CHEK(r) Aviva Expert blood glucose
      meter/bolus advisor system in patients with type 1 diabetes mellitus.
      Hypoglycemia is a major limiting factor to intensive glucose control, and fear of
      hypoglycemia, especially in those who have experienced severe reactions, is a
      major barrier. The bolus advisor improved overall glucose control and increased
      adherence by overcoming the patients' fear of hypoglycemia, giving them more
      confidence to give adequate doses of insulin to control hyperglycemia. In this
      review, we discuss other human factors that become barriers to intensive control,
      which can benefit from new technologies, including numeracy literacy, information
      overload, time required for diabetes self-care, and device incompatibility.

PMID- 22401334
TI  - A simple robust method for estimating the glucose rate of appearance from mixed
      meals.
AB  - BACKGROUND: Estimating the rate of glucose appearance (R(a)) after ingestion of a
      mixed meal may be highly valuable in diabetes management. The gold standard
      technique for estimating R(a) is the use of a multitracer oral glucose protocol.
      However, this technique is complex and is usually not convenient for large
      studies. Alternatively, a simpler approach based on the glucose-insulin minimal
      model is available. The main drawback of this last approach is that it also
      requires a gastrointestinal model, something that may lead to identifiability
      problems. METHODS: In this article, we present an alternative, easy-to-use method
      based on the glucose-insulin minimal model for estimation of R(a). This new
      technique avoids complex experimental protocols by only requiring data from a
      standard meal tolerance test. Unlike other model-based approaches, this new
      approach does not require a gastrointestinal model, which leads to a much simpler
      solution. Furthermore, this novel technique requires the identification of only
      one parameter of the minimal model because the rest of the model parameters are
      considered to have small variability. In order to account for such variability as
      well as to account for errors associated to measurements, interval analysis has
      been employed. RESULTS: The current technique has been validated using data from
      a United States Food and Drug Administration-accepted type 1 diabetes simulator
      [root mean square error (RMSE) = 0.77] and successfully tested with two clinical
      data sets from the literature (RMSE = 0.69). CONCLUSIONS: The presented technique
      for the estimation of R(a) showed excellent results when tested with simulated
      and actual clinical data. The simplicity of this new technique makes it suitable
      for large clinical research studies for the evaluation of the role of R(a) in
      patients with impairments in glucose metabolism. In addition, this technique is
      being used to build a model library of mixed meals that could be incorporated
      into diabetic subject simulators in order to account for more realistic and
      varied meals.

PMID- 22401335
TI  - Pilot study for the evaluation of morphological and functional changes in retinal
      blood flow in patients with insulin resistance and/or type 2 diabetes mellitus.
AB  - BACKGROUND: The aim of this study was to investigate early morphological and
      functional pathology in the retinal micro-circulation in patients with insulin
      resistance and/or type 2 diabetes mellitus (T2DM). METHODS: Fifty-four subjects,
      without features of retinopathy under ophthalmological investigation, were
      recruited for study participation and were classified into three study groups
      according to their metabolic staging: (1) Group C comprised nondiabetic, insulin
      sensitive subjects with a BMI <28 kg/m(2); (2) Group IR comprised nondiabetic,
      insulin-resistant, obese subjects with a BMI >=28 kg/m(2); and (3) Group DM
      comprised patients with manifested T2DM. Retinal microvascular blood flow was
      assessed using scanning laser doppler flowmetry (Heidelberg Retina Flowmeter)
      before and after flicker light stimulation (10 Hz; Photo Stimulater 750).
      RESULTS: No significant difference was observed in retinal blood flow (RBF) among
      the three groups, neither at baseline nor after stimulating the retina with
      flicker light. The arterial wall-to-lumen ratio (WLR) tended to be smaller in
      Group DM compared with Group C, and was significantly lower when comparing Group
      IR with Group C. When the subjects were grouped according to their insulin
      resistance, a steady decline in RBF and WLR could be observed with increasing
      insulin resistance. CONCLUSIONS: In conclusion, laser scanner flowmetry of the
      retina was found to detect very early changes in microvascular blood flow.
      Development of insulin resistance seems to be an important component in the
      deterioration of RBF.

PMID- 22401336
TI  - Closing the gap: eliminating health care disparities among Latinos with diabetes
      using health information technology tools and patient navigators.
AB  - Latinos have higher rates of diabetes and diabetes-related complications compared
      to non-Latinos. Clinical diabetes self-management tools that rely on innovative
      health information technology (HIT) may not be widely used by Latinos,
      particularly those that have low literacy or numeracy, low income, and/or limited
      English proficiency. Prior work has shown that tailored diabetes self-management
      educational interventions are feasible and effective in improving diabetes
      knowledge and physiological measures among Latinos, especially those
      interventions that utilize tailored coaching and navigator programs. In this
      article, we discuss the role of HIT for diabetes management in Latinos and
      describe a novel "eNavigator" role that we are developing to increase HIT
      adoption and thereby reduce health care disparities.

PMID- 22401337
TI  - Thermal threshold: research study on small fiber dysfunction in distal diabetic
      polyneuropathy.
AB  - OBJECTIVE: The most commonly used technique for diagnosis of diabetic neuropathy
      (DN) is nervous conduction (NC). Our hypothesis is that the use of the thermal
      threshold (TT) technique to evaluate small fiber damage, which precedes large
      fiber damage, could enable earlier diagnosis and diminish false negatives.
      RESEARCH DESIGN AND METHODS: The study involved 70 asymptomatic patients with
      type 2 diabetes mellitus (T2DM) all being treated with oral hypoglycemic
      medication, and having negative metabolic control levels with glycosylated
      hemoglobin A1c greater than 7% and less than 8%. Diabetic neuropathy was their
      only evident complication. All other complications or other causes of neuropathy
      were discarded. Their time of evolution was 1 to 48 months since date of
      diagnosis of diabetes. Both thermal threshold and sensory and motor nervous
      conduction were determined in upper and lower limbs. RESULTS: Nervous conduction
      was found normal in 81% and altered in 19% of patients (large fiber neuropathy).
      Thermal threshold was normal in 57% and altered in 43% of patients (small fiber
      neuropathy). In those with normal TTs, no case with an altered NC was found (p <
      0.001). Patients with altered TTs could have normal (57%) or altered NC (43%).
      Thus, NC showed a high frequency of false negatives for DN (57% of 30 cases). The
      frequency of small fiber neuropathy found with the TT test was higher than that
      of large fiber neuropathy found with the NC test (p < 0.001) and was found at an
      earlier age. CONCLUSIONS: The TT test demonstrated a higher frequency of
      neuropathy than the NC test in clinically asymptomatic T2DM patients. We suggest
      that small fiber should be studied before large fiber function to diagnosis
      distal and symmetrical DN.

PMID- 22401338
TI  - Guidelines for application of continuous subcutaneous insulin infusion (insulin
      pump) therapy in the perioperative period.
AB  - Case reports indicate that diabetes patients receiving outpatient insulin pump
      therapy have been allowed to continue treatment during surgical procedures.
      Although allowed during surgery, there is actually little information in the
      medical literature on how to manage patients receiving insulin pump therapy
      during a planned surgical procedure. A multidisciplinary work group reviewed
      current information regarding the use of insulin pumps in the perioperative
      period. Although the work group identified safety issues specific to surgical
      scenarios, it believed that with the use of standardized guidelines and a
      checklist, continuation of insulin pump therapy during the perioperative period
      is feasible. A sample set of protocols have been developed and are summarized. A
      policy outlining clear procedures should be established at the institutional
      level to guide physicians and other staff if the devices are to be employed
      during the perioperative period. Additional clinical experience with the
      technology in surgical scenarios is needed, and consensus should be developed for
      insulin pump use in the perioperative phases of care.

PMID- 22401339
TI  - Continuous glucose monitoring-guided insulin dosing in pump-treated patients with
      type 1 diabetes: a clinical guide.
AB  - This article describes our methods for structured continuous glucose monitoring
      (CGM)-guided insulin dosing in pump-treated type 1 diabetes. Some of the methods
      have been reported and some are based on clinical experience. It is expected that
      this guide will help those involved in the care of such patients and who have
      experience with CGM to achieve better glucose control in their patients. More
      research needs to be done on insulin dosing and we hope that this article will
      also encourage others to pursue this field. This is a guide and, as such, is not
      meant to replace clinical judgment. Also, these dosing approaches apply only to
      those patients on pump therapy. They do not necessarily carry over to those
      patients treated with basal analog insulin.

PMID- 22401340
TI  - Intraoperative fluorescence vascular angiography: during tibial bypass.
AB  - Preventing amputations in persons with lower extremity complications of diabetes
      is a complex endeavor, particularly in those with concomitant ischemia and tissue
      loss. Fluorescence angiography (Novadaq SPY system) may provide a tool for
      objective evaluations of tissue viability in the diabetic foot, which is an
      important indicator of the ability of the diabetic ulcer to heal adequately. The
      SPY system uses a low-power laser coupled with a charge-coupled device camera and
      indocyanine green (ICG) to sequence perfusion at the surface of the skin. We
      present an illustrated example of the potential utility of ICG fluorescence
      angiography (ICGFA) before and after vascular intervention in a high-risk limb.
      ICGFA appeared to reveal demarcation between viable and nonviable tissue and real
      time perfusion, specifically capillary fill. ICGFA clarified the extent of
      necessary debridement and provided an immediate indication of improvement in
      regional perfusion status following revascularization. Future studies involving
      ICGFA may include pre- and postdebridement and closure perfusion, comparison of
      tissue perfusion pre- and post-endovascular therapy, and lower extremity flap
      viability. Future works will also address the consistency of results with ICGFA
      by analyzing a larger cohort of patients being treated by our unit.

PMID- 22401341
TI  - Bioelectrical impedance assessment of wound healing.
AB  - Objective assessment of wound healing is fundamental to evaluate therapeutic and
      nutritional interventions and to identify complications. Despite availability of
      many techniques to monitor wounds, there is a need for a safe, practical,
      accurate, and effective method. A new method is localized bioelectrical impedance
      analysis (BIA) that noninvasively provides information describing cellular
      changes that occur during healing and signal complications to wound healing. This
      article describes the theory and application of localized BIA and provides
      examples of its use among patients with lower leg wounds. This promising method
      may afford clinicians a novel technique for routine monitoring of interventions
      and surveillance of wounds.

PMID- 22401342
TI  - The need for identifying standardized indices for measuring glucose variability.

PMID- 22401345
TI  - Small daily doses of insulin: wasting money?

PMID- 22401344
TI  - Methodology for use of a neuroprosthetic to reduce plantar pressure: applications
      in patients with diabetic foot disease.

PMID- 22401346
TI  - Differences in anti-malarial activity of 4-aminoalcohol quinoline enantiomers and
      investigation of the presumed underlying mechanism of action.
AB  - BACKGROUND: A better anti-malarial efficiency and lower neurotoxicity have been
      reported for mefloquine (MQ) (+)- enantiomer. However, the importance of
      stereoselectivity remains poorly understood as the anti-malarial activity of pure
      enantiomer MQ analogues has never been described. Building on these observations,
      a series of enantiopure 4-aminoalcohol quinoline derivatives has previously been
      synthesized to optimize the efficiency and reduce possible adverse effects. Their
      in vitro activity on Plasmodium falciparum W2 and 3D7 strains is reported here
      along with their inhibition of beta-haematin formation and peroxidative
      degradation of haemin, two possible mechanisms of action of anti-malarial drugs.
      RESULTS: The (S)-enantiomers of this series of 4-aminoalcohol quinoline
      derivatives were found to be at least as effective as both chloroquine (CQ) and
      MQ. The derivative with a 5-carbon side-chain length was the more efficient on
      both P. falciparum strains. (R )-enantiomers displayed an activity decreased by 2
      to 15-fold as compared to their (S) counterparts. The inhibition of beta-haematin
      formation was significantly stronger with all tested compounds than with MQ,
      irrespective of the stereochemistry. Similarly, the inhibition of haemin
      peroxidation was significantly higher for both (S) and (R)-enantiomers of
      derivatives with a side-chain length of five or six carbons than for MQ and CQ.
      CONCLUSIONS: The prominence of stereochemistry in the anti-malarial activity of 4
      aminoalcohol quinoline derivatives is confirmed. The inhibition of beta-haematin
      formation and haemin peroxidation can be put forward as presumed mechanisms of
      action but do not account for the stereoselectivity of action witnessed in vitro.

PMID- 22401347
TI  - Necrotizing fasciitis caused by Serratia marcescens: a fatal complication of
      nephrotic syndrome.
AB  - Necrotizing fasciitis is an uncommon complication of nephrotic syndrome. There
      have been only four cases of necrotizing fasciitis complicating nephrotic
      syndrome reported in the English literature. We report a 40-year-old woman with
      minimal-change nephrotic syndrome receiving cyclosporine therapy, who suffered
      from necrotizing fasciitis of her left leg. Cultures of blood and surgical
      specimens yielded Serratia marcescens. Despite aggressive treatment, the patient
      expired shortly after surgery. We review the literature and find eight cases of
      necrotizing fasciitis caused by S. marcescens. Most of these patients had an
      immunocompromised background, and the mortality rate was high.

PMID- 22401348
TI  - Breast cancer resistance protein (BCRP/ABCG2) localises to the nucleus in
      glioblastoma multiforme cells.
AB  - The breast cancer resistance protein (BCRP), an ATP binding cassette (ABC) efflux
      transporter, plays a role in multiple drug resistance (MDR). Previous studies of
      the subcellular location of the ABC transporter P-glycoprotein indicated that
      this protein is expressed in nuclear membranes. This study examines the nuclear
      distribution of BCRP in seven human-derived glioblastoma (GBM) and astrocytoma
      cell lines. BCRP expression was observed in the nuclear extracts of 6/7 cell
      lines. Using the GBM LN229 cell line as a model, nuclear BCRP protein was
      detected by immunoblotting and confocal laser microscopy. Importantly, nuclear
      BCRP staining was found in a subpopulation of tumour cells in a human brain GBM
      biopsy. Mitoxantrone cytotoxicity in the LN229 cell line was determined with and
      without the BCRP inhibitor fumitremorgin C (FTC) and after downregulation of BCRP
      with small interfering RNA (siRNA). FTC inhibition of BCRP increased mitoxantrone
      cytotoxicity with a ~7-fold reduction in the IC50 and this effect was further
      potentiated in the siRNA-treated cells. In conclusion, BCRP is expressed in the
      nuclear extracts of select GBM and astrocytoma cell lines and in a human GBM
      tumour biopsy. Its presence in the nucleus of cancer cells suggests new role for
      BCRP in MDR.

PMID- 22401350
TI  - Immobilization of enzyme and antibody on ALD-HfO2-EIS structure by NH3 plasma
      treatment.
AB  - Thin hafnium oxide layers deposited by an atomic layer deposition system were
      investigated as the sensing membrane of the electrolyte-insulator-semiconductor
      structure. Moreover, a post-remote NH3 plasma treatment was proposed to replace
      the complicated silanization procedure for enzyme immobilization. Compared to
      conventional methods using chemical procedures, remote NH3 plasma treatment
      reduces the processing steps and time. The results exhibited that urea and
      antigen can be successfully detected, which indicated that the immobilization
      process is correct.

PMID- 22401352
TI  - Parents of children with serious illness are more resilient than credited.

PMID- 22401349
TI  - Applications of imaging technology in radiation research.
AB  - Imaging research and advances in systems engineering have enabled the transition
      of medical imaging from a means for accomplishing traditional anatomic
      visualization (i.e., orthopedic planar film X ray) to a means for noninvasively
      assessing a variety of functional measures. Perfusion imaging is one of the major
      highlights in functional imaging. In this work, various methods for measuring
      perfusion using widely-available commercial imaging modalities and contrast
      agents, specifically X ray and MR (magnetic resonance), will be described. The
      first section reviews general methods used for perfusion imaging, and the second
      section provides modality-specific information, focusing on the contrast
      mechanisms used to calculate perfusion-related parameters. The goal of these
      descriptions is to illustrate how perfusion imaging can be applied to radiation
      biology research.

PMID- 22401353
TI  - Depression, palliative care, and hematologic malignancies: the paradox in low
      income countries.

PMID- 22401354
TI  - When death precedes birth: experience of a palliative care team on a labor and
      delivery unit.
AB  - BACKGROUND: With increasing recognition and availability of palliative care,
      interdisciplinary palliative care teams continue to discover novel opportunities
      to enhance patient-centered care and improve hospital staff satisfaction. As a
      new palliative care consultation service in a large urban academic tertiary care
      setting, we found unanticipated palliative care needs on the labor and delivery
      unit. Women experiencing sudden intrauterine death, and the health care providers
      who care for them, have unique palliative care needs. CONCLUSION: In some
      circumstances an interdisciplinary palliative care team, may help to address
      acute grief and provide ongoing staff support. Case examples of our palliative
      care team's experience are instructive.

PMID- 22401355
TI  - Prevalence of formal accusations of murder and euthanasia against physicians.
AB  - BACKGROUND: Little is known about how often physicians are formally accused of
      hastening patient deaths while practicing palliative care. METHODS: We conducted
      an Internet-based survey on a random 50% sample of physician-members of a
      national hospice and palliative medicine society. RESULTS: The final sample
      consisted of 663 physicians (response rate 53%). Over half of the respondents had
      had at least one experience in the last 5 years in which a patient's family,
      another physician, or another health care professional had characterized
      palliative treatments as being euthanasia, murder, or killing. One in four stated
      that at least one friend or family member, or a patient had similarly
      characterized their treatments. Respondents rated palliative sedation and
      stopping artificial hydration/nutrition as treatments most likely to be
      misconstrued as euthanasia. Overall, 25 physicians (4%) had been formally
      investigated for hastening a patient's death when that had not been their
      intention-13 while using opiates for symptom relief and six for using medications
      while discontinuing mechanical ventilation. In eight (32%) cases, another member
      of the health care team had initiated the charges. At the time of the survey,
      none had been found guilty, but they reported experiencing substantial anger and
      worry. CONCLUSIONS: Commonly used palliative care practices continue to be
      misconstrued as euthanasia or murder, despite this not being the intention of the
      treating physician. Further efforts are needed to explain to the health care
      community and the public that treatments often used to relieve patient suffering
      at the end of life are ethical and legal.

PMID- 22401356
TI  - Parents' thoughts and perceptions on hearing that their child has incurable
      cancer.
AB  - BACKGROUND: Parents of children with incurable cancer face difficulties in making
      end-of-life decisions, and thus far, little research has been conducted on the
      thoughts and perceptions of these parents. PURPOSE: The study aims to describe
      parental thoughts and perceptions when they hear that their child has incurable
      cancer. METHODS: Semi-structured, open-ended interviews were conducted with 23
      parents who had lost children to cancer. A constant comparative content analysis
      was also conducted. RESULTS: Regarding parental thoughts, five categories
      emerged: "not allowing my child to die," "being compelled to continue cancer
      directed/life-sustaining treatment," "wanting to put an end to my child's
      suffering and wanting him/her to be comfortable," "valuing my child's wish and
      dignity," and "wanting to be there for my child." However, some parents did not
      mention all five categories. Regarding parental perceptions of their children's
      condition, six categories emerged: "understanding change/deterioration of my
      child's condition," "recognition of my child's sufferings," "awareness of the
      possible death of my child," "no recognition of my child's impending death as
      reality," "avoiding facing my child's death," and "realizing the truth and coming
      to terms with the reality of death." CONCLUSION: When parents were told that
      their child had incurable cancer, their first thought was to protect their child.
      Because thoughts and perceptions in such a situation vary across parents, health
      care professionals should support parents in realizing their thoughts and
      perceptions and in making decision as parents.

PMID- 22401357
TI  - Palliative care research in Latin America and the Caribbean: from the beginning
      to the Declaration of Venice and beyond.
AB  - BACKGROUND: Research in palliative care has increased significantly in the last
      decade, while the vast majority of the global disease burden occurs in developing
      countries. AIMS: To explore the palliative care research activity in Latin
      America and the Caribbean (LAC) and its visibility in the international
      palliative care literature, with a special focus on research studies. METHODS: A
      bibliometric analysis was conducted in MEDLINE((r)), Embase((r)), PsycINFO((r)),
      and CINAHL((r)). Inclusion criteria were: (1) articles published in peer-reviewed
      scientific journals; (2) main subject was palliative care; (3) research study;
      (4) the first author or coauthors was based in LAC; and/or (5) the data collected
      derived from LAC. RESULTS: One hundred six articles from 10 countries were
      identified in the literature research. The first publication dates from 1989 and
      was a qualitative study in Brazil. This study shows a modest contribution of
      publications from LAC. However, the volume of publications within the region is
      distributed unequally, reflecting the heterogeneity of the region: Brazil
      published more than half of the articles, while 35 countries have no
      publications. Most of the studies were quantitative research, predominantly cross
      sectional studies. Qualitative studies often used interviews. Health care service
      was the most researched issue. Seventy percent of studies were carried out in
      institutions. CONCLUSIONS: Palliative care research should have a place in LAC.
      The development of a regional research agenda tailored to the needs and features
      of the region considering the health care structure and local resources available
      is indispensable.

PMID- 22401358
TI  - Tracheostomy care #250.

PMID- 22401359
TI  - Carotid blowout management #251.

PMID- 22401360
TI  - Hidden suffering.

PMID- 22401361
TI  - Learning to let patients die.

PMID- 22401363
TI  - Redefining success.

PMID- 22401367
TI  - Biomimetic total synthesis of cruentaren A via aromatization of diketodioxinones.
AB  - The total synthesis of cruentaren A, a biologically active resorcylate natural
      product, is reported. The aromatic unit was constructed via late-stage
      cyclization and aromatization from a diketodioxinone intermediate and
      macrocyclization using Furstner ring-closing alkyne metathesis.

PMID- 22401368
TI  - Effects of ovariectomy on rat mandibular cortical bone: a study using Raman
      spectroscopy and multivariate analysis.
AB  - To investigate the effects of ovariectomy (OVX) on rat mandibular bone, the
      physicochemical compositions of mandibular cortical bone of ovariectomy and sham
      operated rats 2, 4, and 8 months after surgery were compared using Raman
      spectroscopy. With principal component analysis and linear discriminant analysis
      based on the Raman spectra, the mandibular cortical bone of the OVX group was
      clearly distinguished from that of the sham-operated group 8 months after surgery
      with no overlap. Specifically, significant reductions in the mineral-to-matrix
      ratio and full width at half-maximum as well as a significant increase in the
      carbonate-to-phosphate ratio were observed in the mandibular cortical bone of the
      OVX group. Results support the hypothesis that Raman spectroscopy is sensitive
      enough to distinguish between OVX and sham-operated mandibles with multivariate
      analysis by detecting the chemical composition of the mandibular cortical bone.
      The parameters mineral-to-matrix ratio, carbonate-to-phosphate ratio, and full
      width at half-maximum can appropriately characterize changes in the chemical
      composition of the mandibular cortical bone after OVX.

PMID- 22401369
TI  - Kinetics and mechanisms for the adsorption, dissociation, and diffusion of
      hydrogen in Ni and Ni/YSZ slabs: a DFT study.
AB  - The adsorption, dissociation, and diffusion of hydrogen in Ni(100) and
      Ni(100)/YSZ(100) slabs with two different interfaces (Ni/cation and Ni/O
      interface) have been studied by the density functional theory (DFT) with the
      Perdew-Wang functional. The H(2) molecule is found to preferentially absorb on a
      Top (T) site with side-on configuration on the Ni(100) surface, while the H-atom
      is strongly bound at a fcc Hollow (H) site. The barrier for the H(2) dissociation
      on both surfaces is calculated to be only ~0.1 eV. The potential energy pathways
      of H diffusion on pure Ni and Ni/YSZ with the two different interfaces are
      studied. Our calculated results show that the H-atom diffusion occurs via surface
      path rather than the bulk path. For the bulk path in Ni/YSZ, H-atom migration can
      occur more readily at the Ni/cation interface compared to the Ni/O interface. The
      existence of vacancy in the interface region is found to improve the mobility of
      H-atoms at the interface of Ni/YSZ slab. The rate constants for hydrogen
      dissociation and diffusion in pure Ni and Ni/YSZ are predicted.

PMID- 22401421
TI  - Communication: epistructural thermodynamics of soluble proteins.
AB  - The epistructural tension of a soluble protein is defined as the reversible work
      per unit area required to span the interfacial solvent envelope of the protein
      structure. It includes an entropic penalty term to account for losses in hydrogen
      bonding coordination of interfacial water and is determined by a scalar field
      that indicates the expected coordination of a test water molecule at any given
      spatial location. An exhaustive analysis of structure-reported monomeric proteins
      reveals that disulfide bridges required to maintain structural integrity provide
      the thermodynamic counterbalance to the epistructural tension, yielding a tight
      linear correlation. Accordingly, deviations from the balance law correlate with
      the thermal denaturation free energies of proteins under reducing conditions. The
      picomolar-affinity toxin HsTX1 has the highest epistructural tension, while the
      metastable cellular form of the human prion protein PrP(C) represents the least
      tension-balanced protein.

PMID- 22401422
TI  - Communication: transition state theory for dissipative systems without a dividing
      surface.
AB  - Transition state theory is a central cornerstone in reaction dynamics. Its key
      step is the identification of a dividing surface that is crossed only once by all
      reactive trajectories. This assumption is often badly violated, especially when
      the reactive system is coupled to an environment. The calculations made in this
      way then overestimate the reaction rate and the results depend critically on the
      choice of the dividing surface. In this Communication, we study the phase space
      of a stochastically driven system close to an energetic barrier in order to
      identify the geometric structure unambiguously determining the reactive
      trajectories, which is then incorporated in a simple rate formula for reactions
      in condensed phase that is both independent of the dividing surface and exact.

PMID- 22401423
TI  - Continuum limit frozen Gaussian approximation for the reduced thermal density
      matrix of dissipative systems.
AB  - A continuum limit frozen Gaussian approximation is formulated for the reduced
      thermal density matrix for dissipative systems. The imaginary time dynamics is
      obtained from a novel generalized Langevin equation for the system coordinates.
      The method is applied to study the thermal density in a double well potential in
      the presence of Ohmic-like friction. We find that the approximation describes
      correctly the delocalization of the density due to quantization of the vibrations
      in the well. It also accounts for the friction induced reduction of the tunneling
      density in the barrier region.

PMID- 22401424
TI  - Coarse-grain model of the benzene ring with para-substituents in the molecule.
AB  - A new two-site coarse-grain model of the benzene ring with substituents in the
      para-position is proposed for use with multiscale simulations. The model uses a
      modified Lennard-Jones potential and introduces an additional shifting parameter
      to the description of the atom-atom interactions. Furthermore, the model
      separates sets of parameters of Van-der-Waals interactions into inter- and
      intramolecular. The shifting parameter is specified separately for each pair of
      atom types for both inter- and intramolecular interactions. The model itself
      consists of two superatoms. It allows for high speed calculations, "remembers"
      the benzene ring orientation in multiscale simulations, and can be used together
      with well-known sets of "united atoms" potentials. This model was tested on p
      xylene, 1-ethyl-4-methylbenzene, and 1-methyl-4-propylbenzene. Structural
      properties for all three substances in the full-atomic model, the "united atoms"
      model, and the suggested coarse-grained model are discussed. The results
      demonstrate that the local structure derived from the coarse-grained model is
      very similar to that derived from the "united atoms" model.

PMID- 22401425
TI  - A numerical solution of the linear Boltzmann equation using cubic B-splines.
AB  - A numerical method using cubic B-splines is presented for solving the linear
      Boltzmann equation. The collision kernel for the system is chosen as the Wigner
      Wilkins kernel. A total of three different representations for the distribution
      function are presented. Eigenvalues and eigenfunctions of the collision matrix
      are obtained for various mass ratios and compared with known values. Distribution
      functions, along with first and second moments, are evaluated for different mass
      and temperature ratios. Overall it is shown that the method is accurate and well
      behaved. In particular, moments can be predicted with very few points if the
      representation is chosen well. This method produces sparse matrices, can be
      easily generalized to higher dimensions, and can be cast into efficient parallel
      algorithms.

PMID- 22401426
TI  - Response calculations based on an independent particle system with the exact one
      particle density matrix: excitation energies.
AB  - Adiabatic response time-dependent density functional theory (TDDFT) suffers from
      the restriction to basically an occupied -> virtual single excitation
      formulation. Adiabatic time-dependent density matrix functional theory allows to
      break away from this restriction. Problematic excitations for TDDFT, viz. bonding
      antibonding, double, charge transfer, and higher excitations, are calculated
      along the bond-dissociation coordinate of the prototype molecules H(2) and HeH(+)
      using the recently developed adiabatic linear response phase-including (PI)
      natural orbital theory (PINO). The possibility to systematically increase the
      scope of the calculation from excitations out of (strongly) occupied into weakly
      occupied ("virtual") natural orbitals to larger ranges of excitations is
      explored. The quality of the PINO response calculations is already much improved
      over TDDFT even when the severest restriction is made, to virtually the size of
      the TDDFT diagonalization problem (only single excitation out of occupied
      orbitals plus all diagonal doubles). Further marked improvement is obtained with
      moderate extension to allow for excitation out of the lumo and lumo+1, which
      become fractionally occupied in particular at longer distances due to left-right
      correlation effects. In the second place the interpretation of density matrix
      response calculations is elucidated. The one-particle reduced density matrix
      response for an excitation is related to the transition density matrix to the
      corresponding excited state. The interpretation of the transition density matrix
      in terms of the familiar excitation character (single excitations, double
      excitations of various types, etc.) is detailed. The adiabatic PINO theory is
      shown to successfully resolve the problematic cases of adiabatic TDDFT when it
      uses a proper PI orbital functional such as the PILS functional.

PMID- 22401427
TI  - Open-system Kohn-Sham density functional theory.
AB  - A simple model for electron transport through molecules is provided by the source
      sink potential (SSP) method [F. Goyer, M. Ernzerhof, and M. Zhuang, J. Chem.
      Phys. 126, 144104 (2007)]. In SSP, the boundary conditions of having an incoming
      and outgoing electron current are enforced through complex potentials that are
      added to the Hamiltonian. Depending on the sign of the imaginary part of the
      potentials, current density is generated or absorbed. In this way, a finite
      system can be used to model infinite molecular electronic devices. The SSP has
      originally been developed for the Huckel method and subsequently it has been
      extended [F. Goyer and M. Ernzerhof, J. Chem. Phys. 134, 174101 (2011)] to the
      Hubbard model. Here we present a step towards its generalization for first
      principles electronic structure theory methods. In particular, drawing on our
      earlier work, we discuss a new generalized density functional theory for complex
      non-Hermitian Hamiltonians. This theory enables us to combine SSP and Kohn-Sham
      theory to obtain a method for the description of open systems that exchange
      current density with their environment. Similarly, the Hartree-Fock method is
      extended to the realm of non-Hermitian, SSP containing Hamiltonians. As a proof
      of principle, we present the first applications of complex-density functional
      theory (CODFT) as well as non-Hermitian Hartree-Fock theory to electron transport
      through molecules.

PMID- 22401428
TI  - Measuring nonadiabaticity of molecular quantum dynamics with quantum fidelity and
      with its efficient semiclassical approximation.
AB  - We propose to measure nonadiabaticity of molecular quantum dynamics rigorously
      with the quantum fidelity between the Born-Oppenheimer and fully nonadiabatic
      dynamics. It is shown that this measure of nonadiabaticity applies in situations
      where other criteria, such as the energy gap criterion or the extent of
      population transfer, fail. We further propose to estimate this quantum fidelity
      efficiently with a generalization of the dephasing representation to multiple
      surfaces. Two variants of the multiple-surface dephasing representation (MSDR)
      are introduced, in which the nuclei are propagated either with the fewest
      switches surface hopping or with the locally mean field dynamics (LMFD). The LMFD
      can be interpreted as the Ehrenfest dynamics of an ensemble of nuclear
      trajectories, and has been used previously in the nonadiabatic semiclassical
      initial value representation. In addition to propagating an ensemble of classical
      trajectories, the MSDR requires evaluating nonadiabatic couplings and solving the
      Schrodinger (or more generally, the quantum Liouville-von Neumann) equation for a
      single discrete degree of freedom. The MSDR can be also used in the diabatic
      basis to measure the importance of the diabatic couplings. The method is tested
      on three model problems introduced by Tully and on a two-surface model of
      dissociation of NaI.

PMID- 22401429
TI  - Rethinking the application of the first nucleation theorem to particle formation.
AB  - The critical cluster is the threshold size above which a cluster will be more
      likely to grow than to evaporate. In field and laboratory measurements of new
      particle formation, the number of molecules of a given species in the critical
      cluster is commonly taken to be the slope of the log-log plot of the formation
      rate versus the concentration of the species. This analysis is based on an
      approximate form of the first nucleation theorem, which is derived with the
      assumption that there are no minima in the free energy surface prior to the
      maximum at the critical size. However, many atmospherically relevant systems are
      likely to exhibit such minima, for example, ions surrounded by condensable vapour
      molecules or certain combinations of acids and bases. We have solved numerically
      the birth-death equations for both an electrically neutral one-component model
      system with a local minimum at pre-critical sizes and an ion-induced case. For
      the ion-induced case, it is verified that the log-log slope of the nucleation
      rate versus particle concentration plot gives accurately the difference between
      the cluster sizes at the free energy maximum and minimum, as is expected from the
      classical form of the ion-induced nucleation rate. However, the results show that
      applying the nucleation theorem to neutral systems with stable pre-nucleation
      clusters may lead to erroneous interpretations about the nature of the critical
      cluster.

PMID- 22401430
TI  - Efficient algorithm of the transcorrelated method for periodic systems.
AB  - The transcorrelated (TC) method is one of the promising wave-function-based
      approaches for the first-principles electronic structure calculations. In this
      method, the many-body wave function is approximated as the Jastrow-Slater type
      and one-electron orbitals in the Slater determinant are optimized with a one-body
      self-consistent-field equation such as that in the Hartree-Fock (HF) method.
      Although the TC method has yielded good results for both molecules and solids,
      its computational cost in solid-state calculations, being of order
      O(N(k)(3)N(b)(3)) with N(k) and N(b) the respective numbers of k-points and
      bands, has for some years hindered its wide application in condensed matter
      physics. Although an efficient algorithm was proposed for a Gaussian basis set,
      that algorithm is not applicable to a plane-wave basis that is suited to and
      widely used in solid-state calculations. In this paper, we present a new
      efficient algorithm of the TC method for the plane-wave basis or an arbitrary
      basis function set expanded in terms of plane waves, with which the computational
      cost of the TC method scales as O(N(k)(2)N(b) (2)). This is the same as that of
      the HF method. We applied the TC method with the new algorithm to obtain
      converged band structure and cell parameters of some semiconductors.

PMID- 22401431
TI  - Rotational excitation of H2O by para-H2 from an adiabatically reduced dimensional
      potential.
AB  - Cross sections and rate coefficients for low lying rotational transitions in
      H(2)O colliding with para-hydrogen pH(2) are computed using an adiabatic
      approximation which reduces the dimensional dynamics from a 5D to a 3D problem.
      Calculations have been performed at the close-coupling level using the recent
      potential of Valiron et al. [J. Chem. Phys. 129, 134306 (2008)]. A good agreement
      is found between the reduced adiabatic calculations and the 5D exact
      calculations, with an impressive time saving and memory gain. This adiabatic
      reduction of dimensionality seems very promising for scattering studies involving
      the excitation of a heavy target molecule by a light molecular projectile.

PMID- 22401432
TI  - Polarization consistent basis sets. VII. The elements K, Ca, Ga, Ge, As, Se, Br,
      and Kr.
AB  - Polarization consistent basis sets, optimized for density functional
      calculations, are proposed for the elements K, Ca, Ga, Ge, As, Se, Br, and Kr.
      The basis set composition in terms of number of primitive functions and the
      contraction is defined based on energetic analyses of atoms and molecules along
      the lines used in previous work and on the performance for molecular systems. The
      performance for atomization energies and dipole moments is compared to other
      widely used basis sets, and it is shown that the new basis sets allow a
      systematic reduction of basis set errors and in general perform better than
      existing ones.

PMID- 22401433
TI  - Conversion of parahydrogen induced longitudinal two-spin order to evenly
      distributed single spin polarisation by optimal control pulse sequences.
AB  - Strongly enhanced spin polarization in the form of longitudinal spin order can be
      generated on target molecules by using parahydrogen in a catalyzed hydrogenation
      reaction. An optimal control algorithm was used to generate radiofrequency pulse
      sequences which convert the arising longitudinal two-spin order into single-spin
      Zeeman order with high efficiency and distribute it evenly between three coupled
      spins within the same molecule. The pulses are designed to be very robust towards
      variations in the B(0) and B(1) fields. Furthermore, this strategy is applied to
      enhance the NMR signal in an ultrafast gradient assisted single excitation two
      dimensional spectroscopy experiment.

PMID- 22401434
TI  - On the triplet ground state of tetrahedral X4 clusters (X = Li, Na, K, Cu).
AB  - The lowest electronic state of distorted tetrahedral X(4) clusters (with X = Li,
      Na, K, Cu) is studied at coupled-cluster level using high-quality atomic basis
      sets. The ground state is found to have a triplet spin symmetry for this kind of
      geometry and for all the considered atomic species. The equilibrium geometries
      correspond to Jahn-Teller-distorted oblate tetrahedra having D(2d) symmetry, and
      tetrahedric structures are local minima on the potential-energy surfaces for the
      triplet states. Their energies lie between 0.2 eV (for the K(4) cluster) and 0.9
      eV (for Cu(4)) above the absolute minimum of the corresponding systems, which is
      a spin singlet having a rhombus geometry.

PMID- 22401435
TI  - Low energy (e,2e) measurements of CH4 and neon in the perpendicular plane.
AB  - Low energy experimental and theoretical triple differential cross sections for
      the highest occupied molecular orbital of methane (1t(2)) and for the 2p atomic
      orbital of neon are presented and compared. These targets are iso-electronic,
      each containing 10 electrons and the chosen orbital within each target has p
      electron character. Observation of the differences and similarities of the cross
      sections for these two species hence gives insight into the different scattering
      mechanisms occurring for atomic and molecular targets. The experiments used
      perpendicular, symmetric kinematics with outgoing electron energies between 1.5
      eV and 30 eV for CH(4) and 2.5 eV and 25 eV for neon. The experimental data from
      these targets are compared with theoretical predictions using a distorted-wave
      Born approximation. Reasonably good agreement is seen between the experiment and
      theory for neon while mixed results are observed for CH(4). This is most likely
      due to approximations of the target orientation made within the model.

PMID- 22401436
TI  - Valence and inner-valence shell dissociative photoionization of CO in the 26-33
      eV range. II. Molecular-frame and recoil-frame photoelectron angular
      distributions.
AB  - Experimental and theoretical results for molecular-frame photoemission are
      presented for inner-valence shell photoionization of the CO molecule induced by
      linearly and circularly polarized light. The experimental recoil frame
      photoelectron angular distributions (RFPADs) obtained from dissociative
      photoionization measurements where the velocities of the ionic fragment and
      photoelectron were detected in coincidence, are compared to RFPADs computed using
      the multichannel Schwinger configuration interaction method. The formalism for
      including a finite lifetime of the predissociative ion state is presented for the
      case of general elliptically polarized light, to obtain the RFPAD rather than the
      molecular frame photoelectron angular distribution (MFPAD), which would be
      obtained with the assumption of instantaneous dissociation. We have considered
      photoionization of CO for the photon energies of 26.0 eV, 29.5 eV, and 32.5 eV. A
      comparison of experimental and theoretical RFPADs allows us to identify the ionic
      states detected in the experimental studies. In addition to previously identified
      states, we found evidence for the 2 (2)Delta state with an ionization potential
      of 25.3 eV and (2)Sigma(+) states with ionization potentials near 32.5 eV. A
      comparison of the experimental and theoretical RFPADs permits us to estimate
      predissociative lifetimes of 0.25-1 ps for some of the ion states. Consideration
      of the MFPADs of a series of (2)Pi ion states indicates the importance of inter
      channel coupling at low photoelectron kinetic energy and the limitations of a
      single-channel analysis based on the corresponding Dyson orbitals.

PMID- 22401437
TI  - Thermal effects on energetics and dynamics in water cluster anions (H2O)n(-).
AB  - The electron binding energies and relaxation dynamics of water cluster anions
      (H(2)O)(n)(-) (11 <= n <= 80) formed in co-expansions with neon were investigated
      using one-photon and time-resolved photoelectron imaging. Unlike previous
      experiments with argon, water cluster anions exhibit only one isomer class, the
      tightly bound isomer I with approximately the same binding energy as clusters
      formed in argon. This result, along with a decrease in the internal conversion
      lifetime of excited (H(2)O)(n)(-) (25 <= n <= 40), indicates that clusters are
      vibrationally warmer when formed in neon. Over the ranges studied, the vertical
      detachment energies and lifetimes appear to converge to previously reported
      values.

PMID- 22401438
TI  - Infrared spectra of CO2-doped hydrogen clusters, (H2)N-CO2.
AB  - Clusters of para-H(2) and/or ortho-H(2) containing a single carbon dioxide
      molecule are studied by high resolution infrared spectroscopy in the 2300 cm(-1)
      region of the CO(2) nu(3) fundamental band. The (H(2))(N)-CO(2) clusters are
      formed in a pulsed supersonic jet expansion from a cooled nozzle and probed using
      a rapid scan tunable diode laser. Simple symmetric rotor type spectra are
      observed with little or no resolved K-structure, and prominent Q-branch features
      for ortho-H(2) but not para-H(2). Observed rotational constants and vibrational
      shifts are reported for ortho-H(2) up to N = 7 and para-H(2) up to N = 15, with
      the N > 7 assignments only made possible with the help of theoretical
      simulations. The para-H(2) cluster with N = 12 shows clear evidence for
      superfluid effects, in good agreement with theory. The presence of larger
      clusters with N > 15 is evident in the spectra, but specific assignments are not
      possible. Mixed para- + ortho-H(2) cluster transitions are well predicted by
      linear interpolation between corresponding pure cluster line positions.

PMID- 22401439
TI  - Outer- and inner-valence satellites of carbon dioxide: electron momentum
      spectroscopy compared with symmetry-adapted-cluster configuration interaction
      general-R calculations.
AB  - The extensive study of outer- and inner-valence satellites of carbon dioxide by
      electron momentum spectroscopy is reported. The experiments have been performed
      using a high-sensitivity electron momentum spectrometer employing non-coplanar
      symmetric geometry at impact energy of about 1200 eV. Binding energy spectrum up
      to 50 eV, above the first double ionization threshold (~37.3 eV), is presented.
      Four main peaks and twelve satellites have been identified including four
      embedded in the double ionization continuum, among which the two beyond 42 eV are
      observed for the first time. High accuracy symmetry-adapted-cluster configuration
      interaction general-R calculation with aug-cc-pVTZ basis sets has also been
      performed and the result is in line with the experimental ionization spectrum
      except the relative intensities for some of the satellites in inner-valence
      region. The experimental momentum profiles for both the main ionization
      transitions and satellites have been obtained and compared with theoretical
      calculations by HF and B3LYP methods with 6-311++G* and aug-cc-pVTZ basis sets.
      Through comparison, the detailed assignments of the satellite bands have been
      achieved and the pole strengths for the relevant shake-up transitions are
      determined experimentally for the first time.

PMID- 22401440
TI  - A new analytical potential energy surface for the singlet state of He2H+.
AB  - The analytic potential energy surface (APES) for the exchange reaction of HeH(+)
      (X(1)Sigma(+)) + He at the lowest singlet state 1(1)A(/) has been built. The APES
      is expressed as Aguado-Paniagua function based on the many-body expansion. Using
      the adaptive non-linear least-squares algorithm, the APES is fitted from 15 682
      ab initio energy points calculated with the multireference configuration
      interaction calculation with a large d-aug-cc-pV5Z basis set. To testify the new
      APES, we calculate the integral cross sections for He + H(+)He (v = 0, 1, 2, j =
      0) -> HeH(+) + He by means of quasi-classical trajectory and compare them with
      the previous result in literature.

PMID- 22401441
TI  - Exact quantum scattering study of the H + HS reaction on a new ab initio
      potential energy surface H2S (3A").
AB  - We present an exact quantum dynamical study and quasi-classical trajectory (QCT)
      calculations for the exchange and abstraction processes for the H + HS reaction.
      These calculations were based on a newly constructed high-quality potential
      energy surface for the lowest triplet state of H(2)S ((3)A"). The ab initio
      single-point energies were computed using complete active space self-consistent
      field and multi-reference configuration interaction method with a basis set of
      aug-cc-pV5Z. The time-dependent wave packet (TDWP) method was used to calculate
      the total reaction probabilities and integral cross sections over the collision
      energy (E(col)) range of 0.0-2.0 eV for the reactant HS initially at the ground
      state and the first vibrationally excited state. It was found that the initial
      vibrational excitation of HS enhances both abstraction and exchange processes. In
      addition, a good agreement is found between QCT and TDWP reaction probabilities
      at the total momentum J = 0 as a function of collision energy for the H + HS (v =
      0, j = 0) reaction.

PMID- 22401442
TI  - The fluoroformyloxyl radical geometry and ground-state rotational spectra of the
      free FC18O2. radical.
AB  - The rotational spectra of the isotopically substituted free fluoroformyloxyl
      radical FC(18)O(2.) were measured using the Prague millimeter-wave high
      resolution spectrometer. More than 110 rotational-fine-hyperfine transition lines
      were observed and assigned to appropriate quantum numbers in the frequency range
      of 235-270 GHz. The obtained transition frequencies were analyzed with standard
      effective Hamiltonians to acquire a set of precise rotational, centrifugal
      distortion, fine, and hyperfine structure molecular constants. Merging the new
      FC(18)O(2.) isotopologue molecular parameters with those previously obtained for
      the ordinary FC(16)O(2)[middle dot] radical, the substitution molecular geometry
      in the ground vibronic state was evaluated. The molecular parameters for both
      radical isotopologues were also calculated by several quantum chemistry methods
      and their calculated mutual ratios are in remarkable agreement with the
      experimental FC(16)O(2.)/FC(18)O(2.) parameter ratios. The measurements,
      assignments of the 18-oxygen isotopologue FC(18)O(2.) radical millimeter-wave
      transitions, as well as the derivation of the fluoroformyloxyl radical ground
      state geometry have been carried out for the first time.

PMID- 22401443
TI  - The electronic states of 1,2,4-triazoles: a study of 1H- and 1-methyl-1,2,4
      triazole by vacuum ultraviolet photoabsorption and ultraviolet photoelectron
      spectroscopy and a comparison with ab initio configuration interaction
      computations.
AB  - The first vacuum ultraviolet absorption spectrum of a 1,2,4-triazole has been
      obtained and analyzed in detail, with assistance from both an enhanced UV
      photoelectron spectroscopic study and ab initio multi-reference multi-root
      configuration interaction procedures. For both 1H- and 1-methyl-1,2,4-triazoles,
      the first ionization energy bands show complex vibrational structure on the low
      energy edges of otherwise unstructured bands. Detailed analysis of these bands
      confirms the presence of three ionized states. The 6-7 eV VUV spectral region
      shows an unusual absorption plateau, which is interpreted in terms of the near
      degeneracy of the first two ionization energies, leading to a pseudo Jahn-Teller
      effect. The "fingerprint" of the ionization spectrum yields band origins for
      several Rydberg states. The configuration interaction study shows that although
      the equilibrium structure for the first cation is effectively planar, the second
      cation shows significant twisting of the ring system. Some calculated singlet
      electronic states also show skeletal twisting in which the ring C-H is
      substantially out of plane.

PMID- 22401444
TI  - A theoretical study on Ta(n)+ cluster cations: structural assignments, stability,
      and electronic properties.
AB  - The low-lying structures of tantalum cluster cations up to n = 16 are
      investigated using hybrid HF/density functional theory (DFT) functionals (B3P86)
      in conjunction with relativistic effective core potential and corresponding basis
      set. The vibrational spectra of tantalum cluster cations are simulated with one
      empirical scaling factor of 0.943, and compared to the experimental ones [P.
      Gruene, A. Fielicke, G. Meijer, J. Chem. Phys. 127, 234307 (2007)]. By assigning
      the vibrational peaks of experimental spectra, the favored geometries actually
      existing in the molecular beam are obtained for several studied clusters. Based
      on the favored geometries, the relative stabilities, spin magnetic moments, and
      electronic dipole moments are determined. Furthermore, spin-related indices
      (omega(s) (+/-)) are computed and found to be good linear correlation with
      vertical lower-upper energy gap.

PMID- 22401445
TI  - Oxygen cluster anions revisited: solvent-mediated dissociation of the core O4(-)
      anion.
AB  - The electronic structure and photochemistry of the O(2n)(-)(H(2)O)(m), n = 1-6, m
      = 0-1 cluster anions is investigated at 532 nm using photoelectron imaging and
      photofragment mass-spectroscopy. The results indicate that both pure oxygen
      clusters and their hydrated counterparts with n >= 2 form an O(4)(-) core.
      Fragmentation of these clusters yields predominantly O(2)(-) and O(2)(-).H(2)O
      anionic products, with the addition of O(4)(-) fragments for larger parent
      clusters. The fragment autodetachment patterns observed for O(6)(-) and larger
      O(2n)(-) species, as well as some of their hydrated counterparts, indicate that
      the corresponding O(2)(-) fragments are formed in excited vibrational states (v
      >= 4). Yet, surprisingly, the unsolvated O(4)(-) anion itself does not show
      fragment autodetachment at 532 nm. It is hypothesized that the vibrationally
      excited O(2)(-) is formed in the intra-cluster photodissociation of the O(4)(-)
      core anion via a charge-hopping electronic relaxation mechanism mediated by
      asymmetric solvation of the nascent photofragments: O(4)(-) -> O(2)(-)(X(2)Pi(g))
      + O(2)(a(1)Delta(g)) -> O(2)(X(3)Sigma(g)(-)) + O(2)(-)(X(2)Pi(g)). This process
      depends on the presence of solvent molecules and leads to vibrationally excited
      O(2)(-)(X(2)Pi(g)) products.

PMID- 22401446
TI  - Diffusion and viscosity of liquid tin: Green-Kubo relationship-based calculations
      from molecular dynamics simulations.
AB  - Molecular dynamics (MD) simulations of liquid tin between its melting point and
      1600  degrees C have been performed in order to interpret and discuss the ionic
      structure. The interactions between ions are described by a new accurate pair
      potential built within the pseudopotential formalism and the linear response
      theory. The calculated structure factor that reflects the main information on the
      local atomic order in liquids is compared to diffraction measurements. Having
      some confidence in the ability of this pair potential to give a good
      representation of the atomic structure, we then focused our attention on the
      investigation of the atomic transport properties through the MD computations of
      the velocity autocorrelation function and stress autocorrelation function. Using
      the Green-Kubo formula (for the first time to our knowledge for liquid tin) we
      determine the macroscopic transport properties from the corresponding microscopic
      time autocorrelation functions. The selfdiffusion coefficient and the shear
      viscosity as functions of temperature are found to be in good agreement with the
      experimental data.

PMID- 22401447
TI  - Time versus temperature rescaling for coarse grain molecular dynamics
      simulations.
AB  - Coarse graining procedures are intended to well reproduce the structure of a
      material while increasing the simulations efficiency. However, the dynamics
      usually accelerates with coarse graining and a scaling procedure has to be used
      for dynamical data calculations. Most often a simple time-scaling coefficient is
      used for this purpose. However, for low temperature liquids this simple scaling
      procedure is questionable. Because supercooled liquids in their approach to the
      glass transition temperature do not follow a simple dynamics. In order to test if
      this scaling procedure is still pertinent at low temperature, we use molecular
      dynamics simulations of a coarse grain model of the methylmethacrylate molecule
      compared to simulations with the All atom model. We compare two different
      rescaling procedures, a time rescale and a temperature rescale procedure. Using
      these two procedures we compare the behaviors of the mean square displacements,
      the incoherent scattering functions, the self and distinct part of the Van Hove
      correlation functions and the non-Gaussian parameters. Results show that the
      temperature rescaling procedure reproduces well the All atom dynamical data at
      low temperatures, while the time rescaling procedure is correct only in the
      Brownian regime. We also find that the melting and the glass-transition
      temperatures are relatively well reproduced with the temperature rescaling
      procedure.

PMID- 22401448
TI  - Flat pancake distant dipolar fields for enhancement of intermolecular multiple
      quantum coherence signals.
AB  - Intermolecular multiple-quantum coherences (iMQCs) originated from distant
      dipolar field (DDF) possess some appealing unique properties for magnetic
      resonance imaging (MRI). DDF is usually induced with continuous wave (i.e., sine-
      or square-wave) magnetization modulation in the whole sample. In this article, a
      spatially localized and enhanced DDF was optimally tailored in a thin slice with
      an adiabatic inversion pulse. Evidence was provided to show that careful
      tailoring of the spatially localized DDF can generate highly efficient iMQC
      signals, with more than two-fold enhancement compared to the conventional sine
      wave magnetization modulation method, and 1.5 times of that with the square-wave
      modulation under the similar condition. Theoretical predictions, simulation
      results, and experimental verifications agree well with each other. Practical
      implementation of this approach for efficient iMQC MRI was explored.

PMID- 22401449
TI  - Thermodynamically consistent closure approximation for hard spheres systems.
AB  - We present a new closure relation that is an extension of the Percus-Yevick
      approximation. In the proposed closure, we introduce an additional term and a
      mixing coefficient that can be determined by imposing a condition of
      thermodynamic self-consistency. Moreover, the mixing coefficient is calculated
      analytically within a linear approximation. In the case of a monodisperse system
      of hard spheres, we compare the results of our model to well-established
      thermodynamic expressions and also to the structural properties of fairly known
      closure approximations. In the second case, and using an equivalent scheme, the
      new closure relation is extended to the depletion potential between two large
      hard spheres immersed in a liquid of small hard spheres. In both cases, the
      results of our model are in good agreement with numerical simulations performed
      at intermediate concentrations.

PMID- 22401450
TI  - Molecular packing in highly stable glasses of vapor-deposited tris
      naphthylbenzene isomers.
AB  - Physical vapor deposition of organic molecules can produce glasses with high
      kinetic stability and low enthalpy. Previous experiments utilizing wide-angle x
      ray scattering (WAXS) have shown that, relative to the ordinary glasses prepared
      by cooling the supercooled liquid, such glasses exhibit excess scattering
      characteristic of anisotropic packing. We have used vapor deposition to prepare
      glasses of four isomers of tris-naphthylbenzene (TNB), and measured both the WAXS
      patterns and the kinetic stability. While vapor-deposited glasses of all four TNB
      isomers exhibit high and nearly uniform kinetic stability, the level of excess
      scattering varies significantly. In addition, for alpha,alpha,beta-TNB, glasses
      of essentially identical kinetic stability can have excess scattering levels that
      vary by a factor of two. These results indicate that anisotropic packing is not
      the source of kinetic stability in vapor-deposited glasses but rather a secondary
      feature that depends upon the chemical structure of the glass-forming molecules.
      We also show that the time required for these stable vapor-deposited glasses to
      transform into the supercooled liquid greatly exceeds the structural relaxation
      time tau(alpha) of the liquid and scales approximately as tau(alpha) (0.6). The
      kinetic stability of the vapor-deposited TNB glasses matches that expected for
      ordinary glasses that have been aged for 10(2) to 10(7) years.

PMID- 22401451
TI  - Pressure-induced dehydration and the structure of ammonia hemihydrate-II.
AB  - The structure of the crystalline ammonia-bearing phase formed when ammonia
      monohydrate liquid is compressed to 3.5(1) GPa at ambient temperature has been
      solved from a combination of synchrotron x-ray single-crystal and neutron powder
      diffraction studies. The solution reveals that rather than having the ammonia
      monohydrate (AMH) composition as had been previously thought, the structure has
      an ammonia hemihydrate composition. The structure is monoclinic with spacegroup
      P2(1)/c and lattice parameters a = 3.3584(5) A, b = 9.215(1) A, c = 8.933(1) A
      and beta = 94.331(8) degrees  at 3.5(1) GPa. The atomic arrangement has a crowned
      hexagonal arrangement and is a layered structure with long N-D...N hydrogen bonds
      linking the layers. The existence of pressure-induced dehydration of AMH may have
      important consequences for the behaviour and differentiation of icy planets and
      satellites.

PMID- 22401452
TI  - Thermodynamics of supercooled water.
AB  - We review the available experimental information on the thermodynamic properties
      of supercooled water and demonstrate the possibility of modeling these
      thermodynamic properties on a theoretical basis. We show that by assuming the
      existence of a liquid-liquid critical point in supercooled water, the theory of
      critical phenomena can give an accurate account of the experimental thermodynamic
      property data up to a pressure of 150 MPa. In addition, we show that a
      phenomenological extension of the theoretical model can account for all currently
      available experimental data in the supercooled region, up to 400 MPa. The
      stability limit of the liquid state and possible coupling between crystallization
      and liquid-liquid separation are also discussed. It is concluded that critical
      point thermodynamics describes the available thermodynamic data for supercooled
      water within experimental accuracy, thus establishing a benchmark for further
      developments in this area.

PMID- 22401453
TI  - Coupling of translational and rotational motion in chiral liquids in
      electromagnetic and circularly polarised electric fields.
AB  - Non-equilibrium molecular dynamics simulations of R and S enantiomers of 1,1
      chlorofluoroethane, both for pure liquids and racemic mixtures, have been
      performed at 298 K in the absence and presence of both electromagnetic (e/m) and
      circularly polarised electric (CP) fields of varying frequency (100-2200 GHz) and
      intensity (0.025-0.2 V A(-1) (rms)). Significant non-thermal field effects were
      noted in the coupling of rotational and translational motion; for instance, in
      microwave and far-infrared (MW/IR) e/m fields, marked increases in rotational and
      translational diffusion vis-a-vis the zero-field case took place at 0.025-0.1 V
      A(-1) (rms), with a reduction in translational diffusion vis-a-vis the zero-field
      case above 0.1 V A(-1) (rms) above 100 GHz. This was due to enhanced direct
      coupling of rotational motion with the more intense e/m field at the ideal
      intrinsic rotational coupling frequency (approximately 700 GHz) leading to such
      rapidly oscillating rotational motion that extent of translational motion was
      effectively reduced. In the case of CP fields, rotational and translational
      diffusion was also enhanced for all intensities, particularly at approximately
      700 GHz. For both MW/IR and CP fields, non-linear field effects were evident
      above around 0.1 V A(-1) (rms) intensity, in terms of enhancements in
      translational and rotational motion. Simulation of 90-10 mol. % liquid mixtures
      of a Lennard-Jones solvent with R and S enantiomer-solutes in MW/IR and CP fields
      led to more limited promotion of rotational and translational diffusion, due
      primarily to increased frictional effects. For both e/m and CP fields,
      examination of the laboratory- and inertial-frame auto- and cross-correlation
      functions of velocity and angular velocity demonstrated the development of
      explicit coupling with the external fields at the applied frequencies, especially
      so in the more intense fields where nonlinear effects come into play. For racemic
      mixtures, elements of the laboratory- and inertial-frame velocity and angular
      velocity were found to couple with each other to a lesser extent.

PMID- 22401454
TI  - Infrared spectroscopy and modeling of co-crystalline CO2.C2H2 aerosol particles.
      I. The formation and decomposition of co-crystalline CO2.C2H2 aerosol particles.
AB  - Aerosol particles composed of co-crystalline CO(2).C(2)H(2) were generated in a
      bath gas cooling cell at cryogenic temperatures and investigated with infrared
      spectroscopy between 600 and 4000 cm(-1). Similar to results obtained for thin
      films of the co-crystal [T. E. Gough and T. E. Rowat, J. Chem. Phys. 109, 6809
      (1998)], this phase was found to be metastable and decomposed into pure CO(2) and
      pure C(2)H(2). These decomposed aerosols were characterized through (i) a
      comparison to experimentally prepared aerosols of mixed CO(2) and C(2)H(2) of
      known architectures and (ii) the modeling of infrared spectra. A likely
      architecture after decomposition are C(2)H(2)-CO(2) core-shell particles with a
      disk-like shape. The co-crystalline CO(2).C(2)H(2) aerosols prior to
      decomposition are modeled and analyzed in detail in the subsequent paper (Part
      II).

PMID- 22401455
TI  - Infrared spectroscopy and modeling of co-crystalline CO2.C2H2 aerosol particles.
      II. The structure and shape of co-crystalline CO2.C2H2 aerosol particles.
AB  - Infrared absorption spectra of co-crystalline CO(2).C(2)H(2) aerosol particles
      were modeled using a combination of two methods. Density functional theory was
      used to model several bulk CO(2).C(2)H(2) co-crystal structures and to calculate
      their lattice energies and frequency-dependent dielectric tensors. This was
      necessary as there currently exists no crystallographic or refractive index data
      on co-crystalline CO(2).C(2)H(2)due to its metastability. The discrete dipole
      approximation was then used to calculate infrared absorption spectra of different
      model particles using the dielectric tensors calculated using density functional
      theory. Results from these simulations were compared to the experimental spectrum
      of co-crystalline CO(2).C(2)H(2) aerosol particles. The aerosol particles after
      the decomposition of the co-crystalline phase were studied in Part I.

PMID- 22401456
TI  - The speed of sound and derived thermodynamic properties of pure water at
      temperatures between (253 and 473) K and at pressures up to 400 MPa.
AB  - The speed of sound in high-purity water has been measured in the temperature
      range (253 to 473) K at pressures up to 400 MPa. The experimental technique used
      was based on a double-path pulse-echo method with a single 5-MHz ultrasound
      transducer placed between two unequally spaced reflectors. The cell was
      calibrated in water at T = 298.15 K and p = 1 MPa against the speed of sound
      given by the 1995 equation-of-state formulation of the International Association
      for the Properties of Water and Steam (IAPWS-95) which, for that state point, has
      an uncertainty of 0.005%. Corrections for the effects of temperature and pressure
      on the path length difference are considered in detail. The estimated expanded
      relative uncertainty of the speed of sound determined in this work is shown to be
      between 0.03% and 0.04% at a confidence level of 95%. The density and isobaric
      specific heat capacity of water have been obtained in the temperature range
      (253.15 to 473.15) K at pressure up to 400 MPa by thermodynamic integration of
      the sound-speed data subject to initial values computed from IAPWS-95 on the
      isobar at p = 0.1 MPa. The speed of sound, density, and isobaric specific heat
      capacity were compared with IAPWS-95 with corresponding absolute relative
      deviations within 0.3%, 0.03%, and 1%, respectively at T >= 273.15 K and p <= 400
      MPa; larger deviations, especially for heat capacity, were found at lower
      temperatures. The results imply that the uncertainties of properties computed
      from IAPWS-95 may be significantly reduced over the major part of the region
      investigated in this work.

PMID- 22401457
TI  - Fluid-fluid and fluid-solid transitions in the Kern-Frenkel model from Barker
      Henderson thermodynamic perturbation theory.
AB  - We study the Kern-Frenkel model for patchy colloids using Barker-Henderson second
      order thermodynamic perturbation theory. The model describes a fluid where hard
      sphere particles are decorated with one patch, so that they interact via a square
      well potential if they are sufficiently close one another, and if patches on each
      particle are properly aligned. Both the gas-liquid and fluid-solid phase
      coexistences are computed and contrasted against corresponding Monte Carlo
      simulations results. We find that the perturbation theory describes rather
      accurately numerical simulations all the way from a fully covered square-well
      potential down to the Janus limit (half coverage). In the region where numerical
      data are not available (from Janus to hard-spheres), the method provides
      estimates of the location of the critical lines that could serve as a guideline
      for further efficient numerical work at these low coverages. A comparison with
      other techniques, such as integral equation theory, highlights the important
      aspect of this methodology in the present context.

PMID- 22401458
TI  - Biaxial order and a rotation of the minor director in the nematic phase of an
      organo-siloxane tetrapode by the electric field.
AB  - Biaxiality in the nematic phase for a liquid crystalline tetrapode made up of
      organo-siloxanes mesogens is investigated using polarized infrared spectroscopy.
      An ordering of the minor director for the homeotropically aligned sample is found
      to depend on the amplitude of the in-plane electric field. On increasing the in
      plane electric field, the minor director, lying initially along the rubbing
      direction, rotates to the direction of the applied field. The scalar order
      parameters of the second rank tensor are found to depend significantly on the
      strength of the electric field. A most significant increase is found in the
      nematic order parameter and in the parameter that characterizes the phase
      biaxiality.

PMID- 22401459
TI  - A statistical model of hydrogen bond networks in liquid alcohols.
AB  - We here present a statistical model of hydrogen bond induced network structures
      in liquid alcohols. The model generalises the Andersson-Schulz-Flory chain model
      to allow also for branched structures. Two bonding probabilities are assigned to
      each hydroxyl group oxygen, where the first is the probability of a lone pair
      accepting an H-bond and the second is the probability that given this bond also
      the second lone pair is bonded. The average hydroxyl group cluster size, cluster
      size distribution, and the number of branches and leaves in the tree-like network
      clusters are directly determined from these probabilities. The applicability of
      the model is tested by comparison to cluster size distributions and bonding
      probabilities obtained from Monte Carlo simulations of the monoalcohols methanol,
      propanol, butanol, and propylene glycol monomethyl ether, the di-alcohol
      propylene glycol, and the tri-alcohol glycerol. We find that the tree model can
      reproduce the cluster size distributions and the bonding probabilities for both
      mono- and poly-alcohols, showing the branched nature of the OH-clusters in these
      liquids. Thus, this statistical model is a useful tool to better understand the
      structure of network forming hydrogen bonded liquids. The model can be applied to
      experimental data, allowing the topology of the clusters to be determined from
      such studies.

PMID- 22401460
TI  - The plastic and liquid phases of CCl3Br studied by molecular dynamics
      simulations.
AB  - We present a molecular dynamics study of the liquid and plastic crystalline
      phases of CCl(3)Br. We investigated the short-range orientational order using a
      recently developed classification method and we found that both phases behave in
      a very similar way. The only differences occur at very short molecular
      separations, which are shown to be very rare. The rotational dynamics was
      explored using time correlation functions of the molecular bonds. We found that
      the relaxation dynamics corresponds to an isotropic diffusive mode for the liquid
      phase but departs from this behavior as the temperature is decreased and the
      system transitions into the plastic phase.

PMID- 22401461
TI  - Two-dimensional-Raman-terahertz spectroscopy of water: theory.
AB  - We discuss the hybrid 2D-Raman-THz spectroscopy of liquid water. This two
      dimensional spectroscopy is designed to directly work in the low-frequency range
      of the intermolecular degrees of freedom. The information content of 2D-Raman-THz
      spectroscopy is similar to 2D-Raman or 2D-THz spectroscopy, but its experimental
      implementation should be easier. That is, 2D-Raman-THz spectroscopy is a 3rd
      order nonlinear spectroscopy and as such completely avoids cascading of
      consecutive 3rd-order signals, which turned out to be a major difficulty in 5th
      order 2D-Raman spectroscopy. On the other hand, it does not require any intense
      THz pump-pulse, the lack of which limits 2D-THz spectroscopy to the study of
      semiconductor quantum wells as the currently available pulse energies are too low
      for molecular systems. In close analogy to 2D-Raman spectroscopy, the 2D-Raman
      THz response of liquid water is simulated from an all-atom molecular dynamics
      simulation, and the expected spectral features are discussed.

PMID- 22401462
TI  - Phase transition in porous electrodes. II. Effect of asymmetry in the ion size.
AB  - The electrochemical thermodynamics of electrolytes in porous electrodes is
      qualitatively different from that in the bulk with planar electrodes when the
      pore size is comparable to the size of the electrolyte ions. In this study, the
      effect of the ion size asymmetry on the thermodynamics in porous electrodes was
      studied by using Monte Carlo simulation. We used the electrolyte ions for which
      the size of the cations and that of anions is different. Due to the asymmetry in
      the ion size, the ionic structure and the way the surface charge is distributed
      on the electrode surfaces were found to be qualitatively different in the cathode
      and in the anode. In particular, for some ranges of applied voltage, the
      distribution of the surface charge induced on the electrode planes shows
      inhomogeneity, which is not intrinsic to the structure of the porous electrodes.
      The transition from the homogeneous to the inhomogeneous distribution of surface
      charge on changing the voltage is a second order phase transition.

PMID- 22401463
TI  - Kinetics of the sulfur oxidation on palladium: a combined in situ x-ray
      photoelectron spectroscopy and density-functional study.
AB  - We studied the reaction kinetics of sulfur oxidation on the Pd(100) surface by in
      situ high resolution x-ray photoelectron spectroscopy and ab initio density
      functional calculations. Isothermal oxidation experiments were performed between
      400 and 500 K for small amounts (~0.02 ML) of preadsorbed sulfur, with oxygen in
      large excess. The main stable reaction intermediate found on the surface is
      SO(4), with SO(2) and SO(3) being only present in minor amounts. Density
      functional calculations depict a reaction energy profile, which explains the
      sequential formation of SO(2), SO(3), and eventually SO(4), also highlighting
      that the in-plane formation of SO from S and O adatoms is the rate limiting step.
      From the experiments we determined the activation energy of the rate limiting
      step to be 85 +/- 6 kJ mol(-1) by Arrhenius analysis, matching the calculated
      endothermicity of the SO formation.

PMID- 22401464
TI  - Simulations of shearing of capillary bridges.
AB  - Capillary bridges are considered as the major source of interaction forces acting
      in wet particulate systems. We study the dynamic shear resistance by using a
      lattice Boltzmann numerical scheme for a binary fluid. The shear resistance force
      showed very little dependence on surface tension and contact angle. Instead, the
      shear resistance is a dynamic phenomenon and a major contributing factor is the
      distortion of the flow field caused by the presence of interfaces. This
      distortion of the flow field is geometry-dependent: in smaller diameter bridges
      the proportion of this distorted flow field becomes larger and it makes a major
      contribution to the shear resistance force. In other words multiple bridges have
      an enhancement effect on shear resistance.

PMID- 22401465
TI  - The effect of step geometry in copper oxidation by hyperthermal O2 molecular
      beam: Cu(511) vs Cu(410).
AB  - Steps are known to be often the active sites for the dissociation of O(2)
      molecules and the nucleation sites of oxide films since they provide paths for
      subsurface migration and oxygen incorporation. In order to unravel the effect of
      their morphology on the oxidation of Cu surfaces, we present here a detailed
      investigation of the O(2) interaction with Cu(511) and compare it with previous
      results for Cu(410), a surface exhibiting terraces of similar size and geometry
      but different step morphology. As for Cu(410) we find, by x-ray photoemission
      spectroscopy performed with synchrotron radiation, that Cu(2)O formation
      gradually starts above half a monolayer oxygen coverage and that the ignition of
      oxidation can be lowered to room temperature by dosing O(2) via a supersonic
      molecular beam at hyperthermal energy. The oxidation rate for Cu(511) comes out
      to be lower than for Cu(410) at normal incidence, about the same when the O(2)
      molecules impinge towards the ascending step rise, but higher when they hit the
      surface along trajectories even slightly inclined towards the descending step
      rise. These findings can be rationalized by a collision induced absorption
      mechanism.

PMID- 22401466
TI  - Current versus temperature-induced switching of a single molecule: open-system
      density matrix theory for 1,5-cyclooctadiene on Si(100).
AB  - The switching of single cyclooctadiene molecules chemisorbed on a Si(100) surface
      between two stable conformations, can be achieved with a scanning tunneling
      microscope [Nacci et al., Phys. Rev. B 77, 121405(R) (2008)]. Recently, it was
      shown by quantum chemical and quantum dynamical simulations that major
      experimental facts can be explained by a single-mode model with switching
      enforced by inelastic electron tunneling (IET) excitations and perturbed by
      vibrational relaxation [Nacci et al., Nano Lett. 9, 2997 (2009)]. In the present
      paper, we extend the previous theoretical work in several respects: (1) The model
      is generalized to a two-mode description in which two C(2)H(4) units of COD can
      move independently; (2) contributions of dipole and, in addition, (cation and
      anion) resonance-IET rates are considered; (3) the harmonic-linear vibrational
      relaxation model used previously is generalized to anharmonic vibrations. While
      the present models highlight generic aspects of IET-switching between two
      potential minima, they also rationalize specific experimental findings for
      COD/Si(100): (1) A single-electron excitation mechanism with a linear dependence
      of the switching rate on tunneling current I, (2) the capability to switch both
      at negative and positive sample biases, and (3) a crossover temperature around
      ~60 K from an IET-driven, T-independent atom tunneling regime, to classical over
      the-barrier isomerization with exponential T-dependence at higher temperatures
      for a bias voltage of +1.5 V and an average tunneling current of 0.73 nA.

PMID- 22401467
TI  - Detailed atomistic Monte Carlo simulations of a polymer melt on a solid surface
      and around a nanoparticle.
AB  - The molecular factors that govern interfacial interactions between a polymer melt
      and a solid surface remain largely unclear despite significant progress made in
      the last years. Simulations are increasingly employed to elucidate these
      features, however, equilibration and sampling with models of long macromolecules
      in such heterogeneous systems present significant challenges. In this study, we
      couple the application of preferential sampling techniques with connectivity
      altering Monte Carlo algorithms to explore the configurational characteristics of
      a polyethylene melt in proximity to a surface and a highly curved nanoparticle.
      Designed algorithms allow efficient sampling at all length scales of large
      systems required to avoid finite-size effects. Using detailed atomistic models
      for the polymer and realistic structures for a silica surface and a fullerene, we
      find that at the extreme limit where particles are comparable to the polymer Kuhn
      segment length, curvature penalizes the formation of long train segments. As a
      result, an increased number of shorter contacts belonging to different chains are
      made competing with the anticipated decrease of the bound layer thickness with
      particle size if polymer adsorbed per unit area remained constant. For very small
      nanoparticles, formation of new train segments cannot compete with the overall
      reduction of adsorbance which is present irrespective of the enthalpic
      interactions; a result that demonstrates the need for an accurate description of
      polymer rigidity at these length scales.

PMID- 22401468
TI  - A study for the static properties of symmetric linear multiblock copolymers under
      poor solvent conditions.
AB  - We use a standard bead-spring model and molecular dynamics simulations to study
      the static properties of symmetric linear multiblock copolymer chains and their
      blocks under poor solvent conditions in a dilute solution from the regime close
      to theta conditions, where the chains adopt a coil-like formation, to the poorer
      solvent regime where the chains collapse obtaining a globular formation and phase
      separation between the blocks occurs. We choose interaction parameters as is done
      for a standard model, i.e., the Lennard-Jones fluid and we consider symmetric
      chains, i.e., the multiblock copolymer consists of an even number n of
      alternating chemically different A and B blocks of the same length N(A) = N(B) =
      N. We show how usual static properties of the individual blocks and the whole
      multiblock chain can reflect the phase behavior of such macromolecules. Also, how
      parameters, such as the number of blocks n can affect properties of the
      individual blocks, when chains are in a poor solvent for a certain range of n. A
      detailed discussion of the static properties of these symmetric multiblock
      copolymers is also given. Our results in combination with recent simulation
      results on the behavior of multiblock copolymer chains provide a complete picture
      for the behavior of these macromolecules under poor solvent conditions, at least
      for this most symmetrical case. Due to the standard choice of our parameters, our
      system can be used as a benchmark for related models, which aim at capturing the
      basic aspects of the behavior of various biological systems.

PMID- 22401469
TI  - Diblock copolymer lamellae on sinusoidal and fractal surfaces.
AB  - A scaling analysis of equilibrium orientation of diblock copolymer molecules on
      fractal surfaces and a brief comparison with a particular experiment is presented
      in this paper. This work is motivated by a recent experimental finding that a
      diblock copolymer film of polystyrene-PMMA, when deposited on a rough substrate,
      can orient its lamellae from a parallel to a perpendicular configuration
      depending on the topographical characteristics of the substrate surface. It was
      found that the RMS height itself is not enough to effect the equilibrium
      configuration, but the fractal dimension of the surface is also important. In
      general, the orientation of lamellae is a function of the the power spectral
      density (PSD) curves of the underlying substrate surface. Assuming the diblock
      lamellae to behave like an Alexander-deGennes brush, we obtain the free energy
      expressions for this brush in both parallel and perpendicular orientations in
      various asymptotic regimes. Comparison of their free energy expressions predicts
      the equilibrium configuration. By examining the PSD curves and using our scaling
      results, we are able to qualitatively explain some aspects of the experimental
      observations regarding the equilibrium orientation of the diblock copolymer
      lamellae on rough surfaces.

PMID- 22401470
TI  - The role of relativity and dispersion controlled inter-chain interaction on the
      band gap of thiophene, selenophene, and tellurophene oligomers.
AB  - Ab initio relativistic density functional theoretical calculations have been
      carried out on pi-conjugated oligomers of increasing length with S, Se, and Te as
      heteroatoms. The band gap of the corresponding polymers has been obtained by
      plotting lowest unoccupied molecular orbital (LUMO)-highest occupied molecular
      orbital (HOMO)gap against the reciprocal of the number of monomer units (1/N) and
      extrapolating the curve to 1/N = 0. With B3LYP functional, we predict that role
      of relativistic correction terms is not very significant in the determination of
      final band gap of thiophene, selenophene, and tellurophene polymer. The origin of
      this observation is provided through the density of states (DOS) analysis which
      manifests that DOS contribution across the Fermi level of these polymers is
      mostly governed by C atoms and as a consequence relativistic correction terms due
      to heavy heteroatom remain insignificant to the band gap modification. We also
      inspected the role of inter-chain interaction in determining the net LUMO-HOMO
      gap of pi-stacked double chain oligomers of increasing length. We have found that
      due to the exciton splitting in the stacked configurations, the LUMO-HOMO gap
      decreases steadily. Furthermore, we have noticed that dispersion force has
      important role in the reduction of the LUMO-HOMO gap of the oligomers studied.

PMID- 22401471
TI  - The role of C-H and C-C stretching modes in the intrinsic non-radiative decay of
      triplet states in a Pt-containing conjugated phenylene ethynylene.
AB  - The intrinsic non-radiative decay (internal conversion) from the triplet excited
      state in phosphorescent dyes can be described by a multi-phonon emission process.
      Since non-radiative decay of triplet excitons can be a significant process in
      organic light-emitting diodes, a detailed understanding of this decay mechanism
      is important if the overall device efficiency is to be controlled. We compare a
      deuterated Pt(II)-containing phenylene ethynylene with its non-deuterated
      counterpart in order to investigate which phonon modes control to the non
      radiative decay path. We observe that deuteration does not decrease the non
      radiative decay rate. A Franck-Condon analysis of the phosphorescence spectra
      shows that the electronic excitation is coupled strongly to the breathing mode of
      the phenyl ring and the C=C carbon stretching modes, while high-energy C-H or C-D
      stretching modes play an insignificant role. We, therefore, associate the
      internal conversion process with the carbon-carbon stretching vibrations.

PMID- 22401472
TI  - DNA conformation in nanochannels: Monte Carlo simulation studies using a
      primitive DNA model.
AB  - We have performed canonical ensemble Monte Carlo simulations of a primitive DNA
      model to study the conformation of 2.56 ~ 21.8 MUm long DNA molecules confined in
      nanochannels at various ionic concentrations with the comparison of our previous
      experimental findings. In the model, the DNA molecule is represented as a chain
      of charged hard spheres connected by fixed bond length and the nanochannels as
      planar hard walls. System potentials consist of explicit electrostatic potential
      along with short-ranged hard-sphere and angle potentials. Our primitive model
      system provides valuable insight into the DNA conformation, which cannot be
      easily obtained from experiments or theories. First, the visualization and
      statistical analysis of DNA molecules in various channel dimensions and ionic
      strengths verified the formation of locally coiled structures such as backfolding
      or hairpin and their significance even in highly stretched states. Although the
      folding events mostly occur within the region of ~0.5 MUm from both chain ends,
      significant portion of the events still take place in the middle region. Second,
      our study also showed that two controlling factors such as channel dimension and
      ionic strength widely used in stretching DNA molecules have different influence
      on the local DNA structure. Ionic strength changes local correlation between
      neighboring monomers by controlling the strength of electrostatic interaction
      (and thus the persistence length of DNA), which leads to more coiled local
      conformation. On the other hand, channel dimension controls the overall stretch
      by applying the geometric constraint to the non-local DNA conformation instead of
      directly affecting local correlation. Third, the molecular weight dependence of
      DNA stretch was observed especially in low stretch regime, which is mainly due to
      the fact that low stretch modes observed in short DNA molecules are not readily
      accessible to much longer DNA molecules, resulting in the increase in the stretch
      of longer DNA molecules.

PMID- 22401474
TI  - Shear bond strength between resin and zirconia with two different silane blends.
AB  - OBJECTIVE: To study in vitro the effect of two cross-linking silanes, bis-1,2
      (triethoxysilyl)ethane and bis[3-(trimethoxysilyl)propyl]amine, blended with an
      organofunctional silane coupling agent, (3-acryloxypropyl)trimethoxysilane, on
      the shear bond strength between resin-composite cement and silicatized zirconia
      after dry storage and thermocycling. MATERIALS AND METHODS: Six tested groups of
      90 samples of yttria stabilized zirconia were used for sample preparation. The
      surfaces of the zirconia were silica-coated. 3M ESPE Sil silane was used as a
      control. Solutions of (3-acryloxypropyl)trimethoxysilane with cross-linking
      silanes bis-1,2-(triethoxysilyl)ethane and bis[3-(trimethoxysilyl)propyl]amine
      were applied onto the surface of silicatized zirconia. 3M ESPE RelyX resin
      composite cement was bonded onto the silicatized and silanized zirconia surface
      and light-cured. Three groups were tested under dry condition and the other three
      groups were tested for thermocycling. The shear bond strength was measured using
      a materials testing instrument. Group mean shear bond strengths were analysed by
      ANOVA at a significant level of p < 0.05. The zirconia surface composition was
      analysed by X-ray Photoelectron Spectroscopy. RESULTS: The highest shear bond
      strength was 11.8 +/- 3.5 MPa for (3-acryloxypropyl)trimethoxysilane blended with
      bis-1,2-(triethoxysilyl)ethane (dry storage). There was a significant difference
      between mean shear bond strength values for (3-acryloxypropyl)trimethoxysilane
      blended with two cross-linking silanes, bis-1,2-(triethoxysilyl)ethane and bis[3
      (trimethoxysilyl)propyl]amine, after thermocycling (p < 3.9 * 10(-8)). Various
      surface treatments of zirconia influenced the surface roughness (p < 4.6 * 10(
      6)). The chemical composition analysis showed there was an increase in silicon
      and oxygen content after sandblasting. CONCLUSIONS: The results suggest that the
      combination of functional (3-acryloxypropyl)trimethoxysilane with cross-linking
      bis[3-(trimethoxysilyl)propyl]amine showed superior hydrolytic stability than
      with bis-1,2-(triethoxysilyl)ethane.

PMID- 22401475
TI  - Epidemiology of fears and specific phobia in adolescence: results from the
      Mexican Adolescent Mental Health Survey.
AB  - BACKGROUND: Specific phobia is among the most common disorders in the general
      adolescent population, but also among the least studied. The objectives of this
      study were to estimate the prevalence of specific fears among adolescents, the
      proportion of those with fears who meet criteria for specific phobia, and the
      proportion who recognize their fears as excessive and to identify comorbidity
      with other disorders and factors associated with severity and treatment. METHOD:
      3,005 youth aged 12 to 17 years participated in the Mexican Adolescent Mental
      Health Survey, a stratified multistage probability sample representative of
      adolescents living in Mexico City in 2005. Fears, specific phobia, and 20 other
      DSM-IV psychiatric disorders were evaluated with the adolescent computerized
      version of the World Mental Health Composite International Diagnostic Interview,
      administered by trained lay interviewers in the participants' homes. Descriptive,
      logistic regression, and discrete-time survival analyses were employed. RESULTS:
      Most adolescents reported at least 1 fear (76.5%); 36.5% of those met lifetime
      criteria for specific phobia, and 27.3% met criteria in the prior 12 months.
      Blood-injection-injury and animal fears were the most common types. Females were
      more likely to report any fear, to have more fear types, and to meet diagnostic
      criteria. Increased numbers of fears were associated with increased odds of
      meeting specific phobia criteria and with increased impairment. Among teens with
      specific phobia, 71.3% recognized their fear as excessive, 9.7% to 12.3% reported
      severe impairment, and only 6.5% had received treatment. Severity of impairment
      and comorbid disorders were associated with treatment seeking. CONCLUSIONS: The
      large percentage of adolescents meeting diagnostic criteria coupled with the low
      proportion with serious impairment suggests that current diagnostic thresholds
      may be too low or not developmentally sensitive. Future research should address
      the nature of impairment for adolescents with specific phobia. Early detection
      and timely treatment are important given that specific phobia is persistent and
      highly comorbid and that few individuals seek treatment.

PMID- 22401476
TI  - Results of the search for personality disorder screening tools: clinical
      implications.
AB  - OBJECTIVE: To examine the characteristics, validity, posttest probabilities, and
      screening capabilities of 8 different instruments used to predict personality
      disorders. METHOD: Screening instruments were examined in 3 prospective,
      observational, test-development studies in 3 random samples of Dutch psychiatric
      outpatients, using the Structured Clinical Interview for DSM-IV Axis II Disorders
      (SCID-II) as the "gold standard." The studies were performed from March 2004 to
      March 2005 (study 1: N = 195, mean age = 32.7 years), October 2006 to January
      2007 (study 2: N = 79, mean age = 34.3 years), and January 2008 to October 2009
      (study 3: N = 102, mean age = 33.7 years). The following 8 assessment instruments
      were examined: 3 short questionnaires (a self-report form of the Standardized
      Assessment of Personality-Abbreviated Scale [SAPAS-SR], the self-report Iowa
      Personality Disorder Screen [IPDS], and a short self-report version of the SCID
      II [S-SCID-II]); 2 longer questionnaires (the self-report SCID-II Personality
      Questionnaire [SCID-II-PQ] and the NEO Five-Factor Inventory [NEO-FFI]); 1 short
      semistructured interview (the Quick Personality Assessment Schedule [PAS-Q]); and
      2 informant-based interviews (the Standardized Assessment of Personality [SAP]
      and the Standardized Assessment of Personality-Abbreviated Scale for Informants
      [SAPAS-INF]). RESULTS: The SCID-II rate of identification of personality
      disorders in the 3 studies was between 48.1% and 64.1%. The SAPAS-SR, the IPDS,
      and the PAS-Q had the best sensitivity (83%, 77%, and 80%, respectively) and
      specificity (80%, 85%, and 82%, respectively). Moreover, these 3 instruments
      correctly classified the largest number of patients. Using the SAPAS-SR, the
      IPDS, or the PAS-Q raises the odds from 50% to between 80% and 84% that a patient
      in a psychiatric outpatient population will receive a personality disorder
      diagnosis. CONCLUSIONS: The results provide evidence for the usefulness of the
      SAPAS-SR, IPDS, and PAS-Q instruments for personality disorder screening. Because
      the PAS-Q takes a longer time and requires qualified personnel to administer it,
      we recommend use of the SAPAS-SR or the self-report version of the IPDS.

PMID- 22401477
TI  - Risperidone-induced dislocation of the temporomandibular joint.

PMID- 22401478
TI  - The tenets of perinatal psychiatry.

PMID- 22401479
TI  - The effect of sertraline add-on to brief dynamic psychotherapy for the treatment
      of postpartum depression: a randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVE: The efficacy of antidepressants in the treatment of mild-to-moderate
      postpartum depression and the possible advantage of the combination of an
      antidepressant and psychotherapy have not been adequately studied. We
      hypothesized that psychotherapy and concurrent antidepressant treatment would be
      more effective than psychotherapy alone in the treatment of postpartum
      depression. METHOD: Women diagnosed with mild-to-moderate severity postpartum
      depression according to DSM-IV-TR criteria were enrolled in an 8-week,
      randomized, double-blind, placebo-controlled study. Participants received 12
      sessions of focused brief dynamic psychotherapy (BDP) concurrently with 8-week
      sertraline or placebo treatment, followed by a 4-week open phase. Primary
      outcomes were depression scores measured by the Montgomery-Asberg Depression
      Rating Scale (MADRS) and remission rates. The study was conducted in a referral
      center from May 2008 to September 2010. RESULTS: Forty of 42 women randomized
      into the study entered the intent-to-treat analysis. A significant time effect
      for the MADRS was observed (F4,35 = 21.3, P < .0001); however, no time-by-group
      effect was found for any outcome measure. Response rates were 70% and 55% for the
      drug and placebo groups, respectively, and remission rates were 65% and 50%,
      respectively, with no significant difference between groups. CONCLUSION: While
      both treatment groups improved significantly, the results of the present study
      did not demonstrate a significant benefit for sertraline over placebo as an add
      on treatment to focused BDP in mild-to-moderate postpartum depression. Because of
      the study's small sample, the results cannot be viewed as definitive, and a much
      larger study is needed to confirm these results. Furthermore, the promising
      potential of focused BDP as an intervention in this population should be studied
      under controlled conditions. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01028482.

PMID- 22401480
TI  - Comments on a consensus regarding diagnostic criteria for neuroleptic malignant
      syndrome.

PMID- 22401481
TI  - Observations from 8 cases of clozapine rechallenge after development of
      myocarditis.

PMID- 22401482
TI  - How the circadian rhythm affects sleep, wakefulness, and overall health:
      background for understanding shift work disorder.
AB  - It is estimated that 15 to 25% of the U.S. labor force works night, evening, or
      rotating shifts. These non-traditional schedules can affect the circadian rhythm,
      a self-sustained rhythm of biological processes that plays an important role in
      modulating sleep/wake function, resulting in circadian rhythm sleep disorder,
      shift work type, usually referred to as shift work disorder. The disorder
      consists of a constant or recurrent pattern of sleep interruption that results in
      insomnia when sleep is needed and excessive sleepiness during waking hours.
      Clinicians need more information about the role of the circadian rhythm in human
      functioning as well as the pathophysiology, prevalence, and consequences of shift
      work disorder, so that they can recognize and diagnose this problem in clinical
      practice.

PMID- 22401483
TI  - Diagnosing bipolar disorder: signs and symptoms.
AB  - Bipolar disorder occurs in up to 2% of the community, but the prevalence is much
      higher among first-degree relatives of individuals with bipolar disorder.
      Following Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,
      Text Revision (DSM-IV-TR) criteria assists clinicians in making an accurate
      diagnosis of bipolar I or bipolar II disorder and in distinguishing bipolar
      disorders from other illnesses such as major depressive disorder, medical
      conditions, and substance use. Additionally, always asking depressed patients
      about mania and using mnemonics to check for symptoms of mania and major
      depression can help physicians accurately diagnose and treat bipolar disorder.

PMID- 22401484
TI  - Addressing nonresponse in schizophrenia.
AB  - Atypical antipsychotics are recommended as first-line treatment for
      schizophrenia, but patients may have little or no response to an initial
      antipsychotic trial. Strategies for managing treatment nonresponse include
      increasing the dose, addressing nonadherence, augmenting the original medication,
      and switching the patient to another medication. Clozapine is recommended for
      patients with schizophrenia who have not responded to 2 other antipsychotic
      trials of adequate duration, but many physicians are hesitant to prescribe
      clozapine due to the complexity of the treatment regimen and the possibility of
      severe adverse effects. However, for patients with resistant schizophrenic
      symptoms, the benefits of clozapine may outweigh the risks. Data show that
      patients have more favorable opinions of clozapine treatment than many physicians
      expect. If clozapine treatment is initiated, physicians should mitigate risk by
      carefully monitoring and addressing side effects.

PMID- 22401485
TI  - Strategies for increasing treatment adherence in bipolar disorder.
AB  - Although bipolar disorder cannot be cured, effective medications are available
      that can shorten the duration of illness episodes and reduce the rates of
      relapse. Unfortunately, treatment nonadherence is common among patients with
      bipolar disorder. Factors contributing to nonadherence vary, and nonadherence can
      be deliberate or accidental. Strategies to improve medication adherence include
      forming a strong alliance with patients, educating patients and their caregivers
      about the disorder and the importance of adherence, simplifying medication
      regimens, monitoring tolerability and proactively addressing adverse effects, and
      treating comorbid illnesses.

PMID- 22401486
TI  - Independent data and safety monitoring in psychiatric intervention research.
AB  - A data and safety monitoring board (DSMB) is a multidisciplinary group of
      scientists that monitors a randomized clinical trial. Although DSMBs have been
      used for clinical trials in cardiology, oncology, and infectious disease for
      decades, it was not until the late 1990s that the National Institute of Mental
      Health (NIMH) initially required a DSMB for some of its larger trials. The NIMH
      mandate expanded during the succeeding decade to require DSMBs for many of the
      clinical trials in psychiatry. In turn, the need for board members has grown
      quickly. The objective of this commentary is to consider the purpose of a DSMB
      and to describe its roles, responsibilities, composition, and implementation. The
      rationale for a DSMB is to ensure the integrity and validity of the trial and,
      most importantly, to protect the safety of trial participants. A board conducts
      comprehensive reviews of accumulating unblinded data for safety and, in some
      trials, for efficacy. Reviewers examine adverse events and serious adverse events
      at regular intervals during the course of the trial. In addition, a DSMB monitors
      recruitment, randomization, retention, adherence, and follow-up in an effort to
      evaluate the validity of a trial. Because it is unethical to expose a participant
      to the risks of an experiment that will be unable to answer the scientific
      question that was postulated, a board should also evaluate the study protocol
      prior to trial commencement. Ultimately, a DSMB's responsibilities are broader
      than that of the trial being monitored. It will protect potential study
      participants and eventually could affect patients seeking clinical treatment for
      the disorder being studied.

PMID- 22401487
TI  - The stressor criterion for posttraumatic stress disorder: does it matter?
AB  - OBJECTIVE: The definition of the stressor criterion (DSM criterion A1) for
      posttraumatic stress disorder (PTSD) is hotly debated with major revisions being
      considered for DSM-5. We examine whether symptoms, course, and consequences of
      PTSD vary predictably with the type of stressful event that precipitates
      symptoms. METHOD: We used data from the 2009 PTSD diagnostic subsample (N =
      3,013) of women from the Nurses' Health Study II. We asked respondents about
      exposure to stressful events that qualified under DSM-III or DSM-IV or did not
      qualify under DSM criterion A1. Respondents selected the event they considered
      worst and reported subsequent PTSD symptoms. Among participants who met all other
      DSM-IV PTSD criteria, we compared distress, symptom severity, duration,
      impairment, receipt of professional help, and 9 physical, behavioral, and
      psychiatric sequelae (eg, physical functioning, unemployment, depression) by
      precipitating event group. Various assessment tools were used to determine
      fulfillment of PTSD criteria B through F and to assess these 14 outcomes.
      RESULTS: Participants with PTSD from DSM-III events reported, on average, 1 more
      symptom (DSM-III, mean = 11.8 symptoms; DSM-IV, mean = 10.7 [P < .001]; non-DSM,
      mean = 10.9 [P < .01]) and more often reported that symptoms lasted 1 year or
      longer compared to participants with PTSD from other groups (DSM-III vs DSM-IV, P
      < .01; DSM-III vs non-DSM, P < .001). However, sequelae of PTSD did not vary
      systematically with precipitating event type. CONCLUSIONS: Results indicate the
      stressor criterion as defined by the DSM may not be informative in characterizing
      PTSD symptoms and sequelae. In the context of ongoing DSM-5 revision, these
      results suggest that criterion A1 could be expanded in DSM-5 without much
      consequence for our understanding of PTSD phenomenology. Events not considered
      qualifying stressors under the DSM produced PTSD as consequential as PTSD
      following DSM-III events, suggesting PTSD may be an aberrantly severe but
      nonspecific stress response syndrome.

PMID- 22401488
TI  - Risk factors for antidepressant-related switch to mania.
AB  - OBJECTIVE: Treatment of bipolar depression with antidepressants is strongly
      debated on the basis of the methodologically poor and insufficient data
      supporting their use and the widely held belief that antidepressants can induce
      new episodes of abnormal mood elevation or accelerate the rate of cycling. The
      present study aimed at identifying clinical risk factors for switch into
      hypomania, mania, or mixed states, within 8 weeks after introduction of an
      antidepressant or after increasing its dosage, in a prospective, longitudinal
      design. METHOD: 221 consecutive DSM-IV-TR depressed bipolar I and II disorder
      patients were treated with antidepressants, which were added to previously
      prescribed mood stabilizers and/or atypical antipsychotics. No patient was on
      antidepressant monotherapy. The patients were enrolled from October 2005 through
      January 2010. The primary outcome was the assessment of switch to mania or
      hypomania within 8 weeks after the introduction or dose increase of an
      antidepressant. Both groups were compared with analysis of variance and chi2
      procedures. RESULTS: Treatment-emergent affective switch was detected in 54
      patients (24.4%) (switch group) while 167 patients (75.6%) (nonswitch group) did
      not experience a treatment-related switch. The main clinical differences
      significantly associated with the occurrence of an antidepressant-related switch,
      after performing logistic regression analysis, were higher rate of previous
      switches (P < .001) in the switch versus the nonswitch group, lower rate of
      responses to antidepressants (P < .001) in the switch versus the nonswitch group,
      and earlier age at onset (P = .026) in the switch versus the nonswitch group.
      DISCUSSION: Bipolar patients with an earlier age at onset and an illness course
      characterized by lower rate of response to antidepressants and higher rate of
      switches into mania or hypomania were found to be the ones with higher switch
      risk. Nevertheless, a greater number of previous antidepressant exposures was not
      associated with the occurrence of an antidepressant-associated switch. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT01503489.

PMID- 22401489
TI  - Sponsorship, antidepressant dose, and outcome in major depressive disorder: meta
      analysis of randomized controlled trials.
AB  - OBJECTIVE: Differences in dosing may influence results of pharmaceutical industry
      sponsored medication trials. This study aims to determine the relationship
      between sponsorship and antidepressant dosing and efficacy in randomized
      controlled trials for major depressive disorder. DATA SOURCES: Trials were
      identified through English-language searches of MEDLINE and PsycINFO (January
      1996-June 2010) using specific drug names and classes and depressive disorder or
      major depression and double blind or double-blind method. Other limitations
      included human subjects and treatment study designs using the clinical queries
      option. Other sources were also searched following a strict set of inclusion and
      exclusion criteria. STUDY SELECTION: Randomized controlled trials were included
      if they examined antidepressant treatment for major depressive disorder, reported
      mean final medication dosages, acknowledged an association with industry, and
      included study arms of medications produced by the associated manufacturer and a
      competitor ("sponsor" and "nonsponsor" arms) (58 trials involving 15,026 patients
      from 101 citations identified). DATA EXTRACTION: Data on dosing, efficacy,
      baseline severity, and adverse events were extracted by 2 of the authors.
      RESULTS: Meta-analyses were used to examine dosing and efficacy data. Using
      consensus guidelines for medication dosing, we determined that sponsor medication
      was dosed relatively higher than nonsponsor medication, in 37% (22/60) of
      comparisons as opposed to 5% (3/60) in which the nonsponsor medication was dosed
      higher (chi22 = 25.9, P < .001). Trials in which sponsor drugs were dosed higher
      than nonsponsor drugs demonstrated higher remission rates for the sponsor drug
      (OR = 1.28, 95% CI = 1.11-1.47, P < .001). These results were confirmed using
      regulatory dosing guidelines. There was no significant correlation between dosing
      or outcome with baseline severity or adverse events. CONCLUSIONS: Sponsor drugs
      are dosed higher than nonsponsor drugs in antidepressant randomized controlled
      trials, and higher dosing is associated with better sponsor drug outcomes in some
      cases.

PMID- 22401490
TI  - "Pump-probe" atom-centered density matrix propagation studies to gauge
      anharmonicity and energy repartitioning in atmospheric reactive adducts: case
      study of the OH + isoprene and OH + butadiene reaction intermediates.
AB  - Time-resolved "pump-probe" ab initio molecular dynamics studies are constructed
      to probe the stability of reaction intermediates, the mechanism of energy
      transfer, and energy repartitioning, for moieties involved during the interaction
      of volatile organic compunds with hydroxyl radical. These systems are of prime
      importance in the atmosphere. Specifically, the stability of reaction
      intermediates of hydroxyl radical adducts to isoprene and butadiene molecules is
      used as a case study to develop novel computational techniques involving "pump
      probe" ab initio molecular dynamics. Starting with the various possible hydroxyl
      radical adducts to isoprene and butadiene, select vibrational modes of each of
      the adducts are populated with excess energy to mimic the initial conditions of
      an experiment. The flow of energy into the remaining modes is then probed by
      subjecting the excited adducts to ab initio molecular dynamics simulations. It is
      found that the stability of the adducts arises directly due to the anhormonically
      driven coupling of the modes to facilitate repartitioning of the excess
      vibrational energy. This kind of vibrational repartitioning has a critical
      influence on the energy density.

PMID- 22401491
TI  - Improved execution efficiency of model-based roentgen stereophotogrammetric
      analysis: simplification and segmentation of model meshes.
AB  - Recently, the model-based roentgen stereophotogrammetric analysis (RSA) method
      has been developed as an in vivo tool to estimate static pose and dynamic motion
      of the instrumented prostheses. The two essential inputs for the RSA method are
      prosthetic models and roentgen images. During RSA calculation, the implants are
      often reversely scanned and input in the form of meshes to estimate the outline
      error between prosthetic projection and roentgen images. However, the execution
      efficiency of the RSA iterative calculation may limit its clinical
      practicability, and one reason for inefficiency may be very large number of
      meshes in the model. This study uses two methods of mesh manipulation to improve
      the execution efficiency of RSA calculation. The first is to simplify the model
      meshes and the other is to segment and delete the meshes of insignificant
      regions. An index (i.e. critical percentage) of an optimal element number is
      defined as the trade-off between execution efficiency and result accuracy. The
      predicted results are numerically validated by total knee prosthetic system. The
      outcome shows that the optimal strategy of the mesh manipulation is
      simplification and followed by segmentation. On average, the element number can
      even be reduced to 1% of the original models. After the mesh manipulation, the
      execution efficiency can be increased about 75% without compromising the accuracy
      of the predicted RSA results (the increment of rotation and translation error:
      0.06 degrees  and 0.02 mm). In conclusion, prosthetic models should be
      manipulated by simplification and segmentation methods prior to the RSA
      calculation to increase the execution efficiency and then to improve clinical
      applicability of the RSA method.

PMID- 22401492
TI  - Exploring bikeability in a metropolitan setting: stimulating and hindering
      factors in commuting route environments.
AB  - BACKGROUND: Route environments may influence people's active commuting positively
      and thereby contribute to public health. Assessments of route environments are,
      however, needed in order to better understand the possible relationship between
      active commuting and the route environment. The aim of this study was, therefore,
      to assess the potential associations between perceptions of whether the route
      environment on the whole hinders or stimulates bicycle commuting and perceptions
      of environmental factors. METHODS: The Active Commuting Route Environment Scale
      (ACRES) was used for the assessment of bicycle commuters' perceptions of their
      route environments in the inner urban parts of Greater Stockholm, Sweden. Bicycle
      commuters (n = 827) were recruited by advertisements in newspapers. Simultaneous
      multiple regression analyses were used to assess the relation between predictor
      variables (such as levels of exhaust fumes, noise, traffic speed, traffic
      congestion and greenery) and the outcome variable (hindering - stimulating route
      environments). Two models were run, (Model 1) without and (Model 2) with the item
      traffic: unsafe or safe included as a predictor. RESULTS: Overall, about 40% of
      the variance of hindering - stimulating route environments was explained by the
      environmental predictors in our models (Model 1, R2 = 0.415, and Model 2, R 2=
      0.435). The regression equation for Model 1 was: y = 8.53 + 0.33 ugly or
      beautiful + 0.14 greenery + (-0.14) course of the route + (-0.13) exhaust fumes +
      (-0.09) congestion: all types of vehicles (p <= 0.019). The regression equation
      for Model 2 was y = 6.55 + 0.31 ugly or beautiful + 0.16 traffic: unsafe or safe
      + (-0.13) exhaust fumes + 0.12 greenery + (-0.12) course of the route (p <=
      0.001). CONCLUSIONS: The main results indicate that beautiful, green and safe
      route environments seem to be, independently of each other, stimulating factors
      for bicycle commuting in inner urban areas. On the other hand, exhaust fumes,
      traffic congestion and low 'directness' of the route seem to be hindering
      factors. Furthermore, the overall results illustrate the complexity of a research
      area at the beginning of exploration.

PMID- 22401493
TI  - Infection prevention and control interventions in the first outbreak of
      methicillin-resistant Staphylococcus aureus infections in an equine hospital in
      Sweden.
AB  - BACKGROUND: The first outbreak of methicillin-resistant Staphylococcus aureus
      (MRSA) infection in horses in Sweden occurred in 2008 at the University Animal
      Hospital and highlighted the need for improved infection prevention and control.
      The present study describes interventions and infection prevention control in an
      equine hospital setting July 2008 - April 2010. METHOD: This descriptive study of
      interventions is based on examination of policy documents, medical records, notes
      from meetings and cost estimates. MRSA cases were identified through clinical
      sampling and telephone enquiries about horses post-surgery. Prospective sampling
      in the hospital environment with culture for MRSA and genotyping of isolates by
      spa-typing and pulsed-field gel electrophoresis (PFGE) were performed. RESULTS:
      Interventions focused on interruption of indirect contact spread of MRSA between
      horses via staff and equipment and included: Temporary suspension of elective
      surgery; and identification and isolation of MRSA-infected horses; collaboration
      was initiated between authorities in animal and human public health, human
      medicine infection control and the veterinary hospital; extensive cleaning and
      disinfection was performed; basic hygiene and cleaning policies, staff training,
      equipment modification and interior renovation were implemented over seven
      months.Ten (11%) of 92 surfaces sampled between July 2008 and April 2010 tested
      positive for MRSA spa-type 011, seven of which were from the first of nine
      sampling occasions. PFGE typing showed the isolates to be the outbreak strain (9
      of 10) or a closely related strain. Two new cases of MRSA infection occurred 14
      and 19 months later, but had no proven connections to the outbreak cases.
      CONCLUSIONS: Collaboration between relevant authorities and the veterinary
      hospital and formation of an infection control committee with an executive
      working group were required to move the intervention process forward. Support
      from hospital management and the dedication of staff were essential for the
      development and implementation of new, improved routines. Demonstration of the
      outbreak strain in the environment was useful for interventions such as
      improvement of cleaning routines and interior design, and increased compliance
      with basic hygienic precautions. The interventions led to a reduction in MRSA
      positive samples and the outbreak was considered curbed as no new cases occurred
      for over a year.

PMID- 22401494
TI  - Interaction of tau protein with model lipid membranes induces tau structural
      compaction and membrane disruption.
AB  - The misfolding and aggregation of the intrinsically disordered, microtubule
      associated tau protein into neurofibrillary tangles is implicated in the
      pathogenesis of Alzheimer's disease. However, the mechanisms of tau aggregation
      and toxicity remain unknown. Recent work has shown that anionic lipid membranes
      can induce tau aggregation and that membrane permeabilization may serve as a
      pathway by which protein aggregates exert toxicity, suggesting that the plasma
      membrane may play dual roles in tau pathology. This prompted our investigation to
      assess tau's propensity to interact with membranes and to elucidate the mutually
      disruptive structural perturbations the interactions induce in both tau and the
      membrane. We show that although highly charged and soluble, the full-length tau
      (hTau40) is also highly surface active, selectively inserts into anionic DMPG
      lipid monolayers and induces membrane morphological changes. To resolve molecular
      scale structural details of hTau40 associated with lipid membranes, X-ray and
      neutron scattering techniques are utilized. X-ray reflectivity indicates hTau40s
      presence underneath a DMPG monolayer and penetration into the lipid headgroups
      and tailgroups, whereas grazing incidence X-ray diffraction shows that hTau40
      insertion disrupts lipid packing. Moreover, both air/water and DMPG lipid
      membrane interfaces induce the disordered hTau40 to partially adopt a more
      compact conformation with density similar to that of a folded protein. Neutron
      reflectivity shows that tau completely disrupts supported DMPG bilayers while
      leaving the neutral DPPC bilayer intact. Our results show that hTau40s strong
      interaction with anionic lipids induces tau structural compaction and membrane
      disruption, suggesting possible membrane-based mechanisms of tau aggregation and
      toxicity in neurodegenerative diseases.

PMID- 22401495
TI  - Saharan dust and association between particulate matter and case-specific
      mortality: a case-crossover analysis in Madrid (Spain).
AB  - BACKGROUND: Saharan dust intrusions are a common phenomenon in the Madrid
      atmosphere, leading induce exceedances of the 50 MUg/m(3)--EU 24 h standard for
      PM10. METHODS: We investigated the effects of exposure to PM(10) between January
      2003 and December 2005 in Madrid (Spain) on daily case-specific mortality;
      changes of effects between Saharan and non-Saharan dust days were assessed using
      a time-stratified case-crossover design. RESULTS: Saharan dust affected 20% of
      days in the city of Madrid. Mean concentration of PM(10) was higher during dust
      days (47.7 MUg/m(3)) than non-dust days (31.4 MUg/m(3)). The rise of mortality
      per 10 MUg/m(3) PM(10) concentration were always largely for Saharan dust-days.
      When stratifying by season risks of PM(10), at lag 1, during Saharan dust days
      were stronger for respiratory causes during cold season (IR% = 3.34% (95% CI:
      0.36, 6.41) versus 2.87% (95% CI: 1.30, 4.47)) while for circulatory causes
      effects were stronger during warm season (IR% = 4.19% (95% CI: 1.34, 7.13) versus
      2.65% (95% CI: 0.12, 5.23)). No effects were found for cerebrovascular causes.
      CONCLUSIONS: We found evidence of strongest effects of particulate matter during
      Saharan dust days, providing a suggestion of effect modification, even though
      interaction terms were not statistically significant. Further investigation is
      needed to understand the mechanism by which Saharan dust increases mortality.

PMID- 22401496
TI  - Endothelial function improves within 6 weeks of treatment with methotrexate or
      methotrexate in combination with a TNF-alpha inhibitor in rheumatoid arthritis
      patients.

PMID- 22401497
TI  - A citywide smoking ban reduced maternal smoking and risk for preterm births: a
      Colorado natural experiment.
AB  - BACKGROUND: Few reports exist on the association of a public smoking ban with
      fetal outcomes and maternal smoking in the United States. We sought to evaluate
      the effect of a citywide smoking ban in comparison to a like municipality with no
      such ban in Colorado on maternal smoking and subsequent fetal birth outcomes.
      METHODS: A citywide smoking ban in Colorado provided a natural experiment. The
      experimental citywide smoking ban site was implemented in Pueblo, Colorado. A
      comparison community was chosen that had no smoking ban, El Paso County, with
      similar characteristics of population, size, and geography. The two sites served
      as their own controls, as each had a preban and postban retrospective observation
      period: preban was April 1, 2001, to July 1, 2003; postban was April 1, 2004, to
      July 1, 2006. Outcomes were maternal smoking (self-report), low birth weight
      (LBW) (defined as <2500 g or as <3000 g), and preterm births (<37 weeks
      gestation) in singleton births from mothers residing in these cities and reported
      to the State Department of Public Health. A difference-in-differences estimator
      was used to account for site and temporal trends in multivariate models. RESULTS:
      Compared to El Paso County preban, the odds of maternal smoking and preterm
      births were, respectively, 38% (p<0.05) and 23% (p<0.05) lower in Pueblo. The
      odds for LBW births decreased by 8% for <3000 g and increased by 8.4% for <2500
      g; however, neither was significant. CONCLUSIONS: This is the first evidence in
      the United States that population-level intervention using a smoking ban improved
      maternal and fetal outcomes, measured as maternal smoking and preterm births.

PMID- 22401498
TI  - Inflammation and cardiovascular risk in women with preterm labor.
AB  - BACKGROUND: Women with a history of preterm delivery have about twice the normal
      risk of cardiovascular disease (CVD). Mechanisms underlying this association are
      not well understood. The aim of the present study was to evaluate the
      relationships between selected metabolic CVD risk factors and markers of both
      systemic inflammation and endothelial dysfunction in women with spontaneous
      preterm labor (sPL). METHODS: This was a case-control study in a university
      tertiary referral center. Forty pregnant women with sPL were compared to 50
      controls during gestation. Maternal serum triglycerides, high-density lipoprotein
      cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total
      cholesterol, glycemia, insulinemia, homeostasis model assessment (HOMA), leptin,
      tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), soluble vascular
      cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM),
      selectin, and myeloperoxidase (MPO) were measured. RESULTS: Gestational age at
      study was similar in both groups (31.56+/-3.14 weeks of gestation vs. 31.27+/
      2.14 weeks of gestation, p=0.62, for the control and the sPL groups,
      respectively). Body mass index (BMI) (21.72+/-2.99 vs. 23.56+/-3.80, p=0.01), all
      cholesterol fractions (HDL-C 53.44+/-18.22 vs. 68.32+/-18.38, p=0.0003; LDL-C
      125.71+/-35.56 vs. 142.15+/-36.07, p=0.03, and total cholesterol 219.55+/-32.29
      vs. 240.38+/-40.01, p=0.009) and MPO (3.07+/-0.63 vs. 3.48+/-0.32, p=0.0009) were
      significantly lower in women with sPL. Serum levels of IL-6 (0.61+/-0.46 vs.
      0.33+/-0.46, p=0.007) and the ratio of total cholesterol/HDL-C (4.52+/-1.48 vs.
      3.77+/-1.37, p=0.01) were significantly increased and correlated each other
      (r=0.21, p=0.04). Logistic regression showed that the best predictive model for
      sPL (R(2)=0.36, p=0.001) included BMI and total cholesterol. CONCLUSIONS: A
      combination of low maternal BMI, low cholesterol levels, and high total
      cholesterol/HDL-C ratio is present in women with sPL and is related to
      inflammation.

PMID- 22401499
TI  - IgA variant of anti-glomerular basement membrane glomerulonephritis associated
      with pulmonary hemorrhage and microangiopathic hemolytic anemia.
AB  - A 70-year-old man with uremia was referred because of hemoptysis. A chest X-ray
      showed diffuse infiltration in the right lung field. Laboratory data were
      remarkable for renal failure, anemia, and thrombocytopenia. Furthermore,
      laboratory evidence of microangiopathic hemolytic anemia was present. A kidney
      biopsy revealed diffuse crescentic glomerulonephritis with linear staining of IgA
      along the glomerular basement membrane (GBM). No thrombotic microangiopathy was
      noted on renal biopsy. Circulating IgG anti-GBM antibody was not detected, and
      IgA anti-GBM antibody was not tested. The patient was treated with plasmapheresis
      and pulse steroid therapy, which resulted in an immediate improvement in the
      pulmonary hemorrhage and hematological abnormalities. However, the patient did
      not regain renal function and remained on hemodialysis.

PMID- 22401500
TI  - Rapid identification of Mycobacterium tuberculosis infection by a new array
      format-based surface plasmon resonance method.
AB  - Tubercle bacillus [TB] is one of the most important chronic infectious diseases
      that cause millions of deaths annually. While conventional smear microscopy and
      culture methods are widely used for diagnosis of TB, the former is insensitive,
      and the latter takes up to 6 to 8 weeks to provide a result, limiting the value
      of these methods in aiding diagnosis and intermediate decisions on treatment.
      Therefore, a rapid detection method is essential for the diagnosis, prognosis
      assessment, and recurrence monitoring. A new surface plasmon resonance [SPR]
      biosensor based on an array format, which allowed immobilizing nine TB antigens
      onto the sensor chip, was constructed. Simultaneous determination of multiple TB
      antibodies in serum had been accomplished with this array-based SPR system. The
      results were compared with enzyme-linked immunosorbent assay, a conventional
      immunological method. Array-based SPR showed more advantages in providing label
      free and real-time detection. Additionally, the high sensitivity and specificity
      for the detection of TB infection showed its potential for future development of
      biosensor arrays for TB diagnosis.

PMID- 22401501
TI  - Implanted biofuel cell operating in a living snail.
AB  - Implantable biofuel cells have been suggested as sustainable micropower sources
      operating in living organisms, but such bioelectronic systems are still exotic
      and very challenging to design. Very few examples of abiotic and enzyme-based
      biofuel cells operating in animals in vivo have been reported. Implantation of
      biocatalytic electrodes and extraction of electrical power from small living
      creatures is even more difficult and has not been achieved to date. Here we
      report on the first implanted biofuel cell continuously operating in a snail and
      producing electrical power over a long period of time using physiologically
      produced glucose as a fuel. The "electrified" snail, being a biotechnological
      living "device", was able to regenerate glucose consumed by biocatalytic
      electrodes, upon appropriate feeding and relaxing, and then produce a new
      "portion" of electrical energy. The snail with the implanted biofuel cell will be
      able to operate in a natural environment, producing sustainable electrical
      micropower for activating various bioelectronic devices.

PMID- 22401502
TI  - Dramatically enhanced oxygen uptake and ionization yield of positive secondary
      ions with C60+ sputtering.
AB  - To explore C(60)(+) sputtering beyond low-damage depth profiling of organic
      materials, X-ray photoelectron spectrometry (XPS) and secondary ion mass
      spectrometry (SIMS) were used to examine metallic surfaces during and after
      C(60)(+) sputtering. During C(60)(+) sputtering, XPS spectra indicated that the
      degrees of carbon deposition were different for different metallic surfaces.
      Moreover, for some metals (e.g., Al, W, Ta, Ti, and Mo), the intensity of the O
      1s photoelectron increased significantly during C(60)(+) sputtering, even though
      the instrument was under ultrahigh vacuum (<5 * 10(-7) Pa). This result indicated
      that the rate of oxygen uptake was greater than the rate of C(60)(+) sputtering.
      This behavior was not observed with the commonly used Ar(+) sputtering. To
      measure the oxygen uptake kinetics, pure oxygen was leaked into the chamber to
      maintain a 5 * 10(-6) Pa oxygen environment. The C(60)(+)-sputtered surface had a
      clearly increased rate of oxygen uptake than the Ar(+)-sputtered surface, even
      for moderately reactive metals such as Fe and Ni. For relatively nonreactive
      metals such as Cu and Au, a small amount of carbon was implanted and no oxygen
      uptake was observed. High-resolution XPS spectra revealed the formation of metal
      carbides on these reactive metals, and the carbon deposition and enhanced uptake
      of oxygen correlated to the carbide formation. Because oxygen enhances the
      secondary ion yield through surface passivation, the enhanced oxygen uptake due
      to C(60)(+) sputtering could be beneficial for SIMS analysis. To examine this
      hypothesis, C(60)(+) and Ar(+) were used as primary ions, and it was found that
      the intensity enhancement (because of the oxygen flooding at 5 * 10(-6) Pa) was
      much higher with C(60)(+) than with Ar(+). Therefore, oxygen flooding during
      C(60)(+) sputtering has a great potential for enhancing the detection limit due
      to the enhanced oxygen uptake.

PMID- 22401503
TI  - Increased detection of Mycoplasma pneumoniae infection in children, Lyon, France,
      2010 to 2011.
AB  - Recent reports from several northern European countries indicate an increase in
      detection of Mycoplasma pneumoniae infection in the past two years, notably in
      children aged 5-15 years. Analysis of our laboratory database showed a similar
      pattern, with a higher proportion of respiratory samples positive for M.
      pneumonia by real-time PCR in paediatric patients aged 5-15 years. Our data
      indicate that in 2010 and 2011, France experienced the first epidemic peak of M.
      pneumonia infection since 2005.

PMID- 22401504
TI  - Ongoing epidemic of Mycoplasma pneumoniae infection in Jerusalem, Israel, 2010 to
      2012.
AB  - A substantial epidemic of Mycoplasma pneumonia infection was reported in late
      2011 in some European countries. We report here an epidemic of M. pneumonia
      infection that began in Jerusalem during 2010 and is still ongoing. This report
      complements current information on what might be a worldwide epidemic of M.
      pneumoniae infection that might require substantial coordinated international
      public health intervention.

PMID- 22401505
TI  - First detection of tick-borne "Candidatus Neoehrlichia mikurensis" in Denmark
      2011.
AB  - This is the first reporting of the tick-borne zoonotic bacterium "Candidatus
      Neoehrlichia mikurensis" in Denmark. A total of 2,625 Ixodes ricinus ticks from
      58 locations in Denmark were collected and analysed for "Ca. Neoehrlichia
      mikurensis". A nested PCR revealed the presence of the bacterium at three
      geographically separate locations, which indicates that it is widely established
      in ticks.

PMID- 22401506
TI  - Preliminary report: outbreak of Legionnaires disease in a hotel in Calp, Spain,
      update on 22 February 2012.
AB  - Research is ongoing on eighteen cases of Legionellosis, including four deaths,
      identified among tourists and employees in a hotel in Calp, Spain. Cases occurred
      during a period of two months, indicating the possibility of a point-source
      transmission at the hotel. An environmental investigation identified several
      positive samples in the hotel, which as a precautionary measure, was closed until
      requested improvements were made. Surveillance measures currently remain active.

PMID- 22401507
TI  - Wellness centres: an important but overlooked source of Legionnaires  disease.
      Eight years of source investigation in the Netherlands, 1 August 2002 to 1 August
      2010.
AB  - Visiting wellness centres is considered safe and relaxing and might provide
      health benefits for visitors with certain cardiovascular, dermatological or
      respiratory diseases. On the other hand, wellness centres could pose health
      risks, especially with respect to Legionnaires' disease. We investigated the role
      of wellness centres in the occurrence of Legionnaires' disease by analysing the
      data of eight years (2002-2010) of source investigation in the Netherlands. There
      were 15 wellness centres identified as potential sources of infection for a total
      of 35 Legionnaires' disease patients. Twelve of these centres were positive for
      Legionella spp.: six for Legionella pneumophila, six for non-pneumophila
      Legionella spp.. Of the 65 positive environmental samples found during the
      wellness centre investigations, 41 were derived from shower heads. For two
      centres, the Legionella pneumophila strains in the collected samples had a
      genotype that was indistinguishable from the patient isolates. These results show
      that wellness centres are potential sources of Legionnaires' disease.

PMID- 22401508
TI  - Surveillance of acute infectious gastroenteritis (1992-2009) and food-borne
      disease outbreaks (1996-2009) in Italy, with a focus on the Piedmont and Lombardy
      regions.
AB  - We describe trends in the occurrence of acute infectious gastroenteritis (1992 to
      2009) and food-borne disease outbreaks (1996 to 2009) in Italy. In 2002, the
      Piedmont region implemented a surveillance system for early detection and control
      of food-borne disease outbreaks; in 2004, the Lombardy region implemented a
      system for surveillance of all notifiable human infectious diseases. Both systems
      are internet based. We compared the regional figures with the national mean using
      official notification data provided by the National Infectious Diseases
      Notification System (SIMI) and the National Institute of Statistics (ISTAT), in
      order to provide additional information about the epidemiology of these diseases
      in Italy. When compared with the national mean, data from the two regional
      systems showed a significant increase in notification rates of non-typhoid
      salmonellosis and infectious diarrhea other than non-typhoid salmonellosis, but
      for foodborne disease outbreaks, the increase was not statistically significant.
      Although the two regional systems have different objectives and structures, they
      showed improved sensitivity regarding notification of cases of acute infectious
      gastroenteritis and, to a lesser extent, food-borne disease outbreaks, and thus
      provide a more complete picture of the epidemiology of these diseases in Italy.

PMID- 22401510
TI  - Perceived discrimination and hypertension among African Americans in the Jackson
      Heart Study.
AB  - OBJECTIVES: Using Jackson Heart Study data, we examined whether perceived
      discrimination was associated with prevalent hypertension in African Americans.
      METHODS: Everyday discrimination, lifetime discrimination, burden of
      discrimination, and stress from discrimination were examined among 4939
      participants aged 35 to 84 years (women = 3123; men = 1816). We estimated
      prevalence ratios of hypertension by discrimination, and adjusted for age,
      gender, socioeconomic status, and risk factors. RESULTS: The prevalence of
      hypertension was 64.0% in women and 59.7% in men. After adjustment for age,
      gender, and socioeconomic status, lifetime discrimination and burden of
      discrimination were associated with greater hypertension prevalence (prevalence
      ratios for highest vs lowest quartile were 1.08 [95% confidence interval (CI) =
      1.02, 1.15] and 1.09 [95% CI = 1.02,1.16] for lifetime discrimination and burden
      of discrimination, respectively). Associations were slightly weakened after
      adjustment for body mass index and behavioral factors. No associations were
      observed for everyday discrimination. CONCLUSIONS: Further understanding the role
      of perceived discrimination in the etiology of hypertension may be beneficial in
      eliminating hypertension disparities.

PMID- 22401511
TI  - Social capital and smoking among Asian American men: an exploratory study.
AB  - OBJECTIVES: We examined how different dimensions of social capital (i.e., family
      and friend connections, neighborhood and family cohesion, family conflict) were
      associated with smoking behavior among a nationally representative sample of
      Asian American men and whether the associations varied by ethnic group. METHODS:
      The sample consisted of 998 adult Asian American men who participated in the
      National Latino and Asian American Survey from 2002 to 2003. We conducted
      weighted multivariate logistic regressions on data for the sample and for each of
      4 ethnic subgroups (Chinese, Vietnamese, Filipino, and Other). RESULTS:
      Vietnamese American men had the highest prevalence of current smoking; Chinese
      American men, the lowest. After controlling for sociodemographics, socioeconomic
      status, acculturation, and perceived discrimination, neighborhood cohesion was
      inversely associated with smoking among Asian American men, and family and friend
      connections and family cohesion were not. An exception was family cohesion, which
      was associated with increased odds of smoking among Filipino American men.
      CONCLUSIONS: The relationship between social capital and smoking among Asian
      American men varied according to specific dimensions of social capital and was
      ethnicity specific. These findings highlight the need for smoking prevention and
      cessation interventions to take into consideration the heterogeneity that exists
      among Asian Americans.

PMID- 22401512
TI  - Health in working-aged Americans: adults with high school equivalency diploma are
      similar to dropouts, not high school graduates.
AB  - OBJECTIVES: We compared health outcomes for adults with the General Equivalency
      Diploma (GED) and regular high school diploma to determine whether GED recipients
      are equivalent to regular graduates despite research that documents their
      disadvantages in other outcomes. METHODS: We used 1997 to 2009 National Health
      Interview Survey cross-sectional data on high school dropouts, graduates, and GED
      recipients aged 30 to 65 years (n = 76,705). Five general health indicators and
      20 health conditions were analyzed using logistic models. RESULTS: GED recipients
      had a significantly higher prevalence of every health outcome compared with high
      school graduates (odds ratios = 1.3-2.7). The GED-high school differences
      attenuated but remained evident after controlling for health insurance, economic
      status, and health behaviors. For most conditions, the 95% confidence interval
      for GED earners overlapped with that for high school dropouts. CONCLUSIONS: The
      high school equivalency diploma was associated with nonequivalent health: adults
      with a GED had health comparable to that of high school dropouts, not graduates.
      GED recipients were at increased risk for many health conditions, and their
      health should be viewed as distinct from regular graduates. The findings have
      implications for health and educational policies.

PMID- 22401513
TI  - Shared communities, structural contexts, and HIV risk: prioritizing the HIV risk
      and prevention needs of Black heterosexual men.
AB  - Black heterosexual men (BHM) are seldom mentioned in HIV prevention research,
      policy, and interventions, despite evidence that heterosexual contact is becoming
      the leading exposure category for BHM.  The disparate effect of HIV/AIDS on BHM;
      the debunked "down low" myth; the contexts of BHM's lives in terms of
      disproportionate poverty, unemployment, and incarceration; and a growing
      empirical base linking these factors to increased HIV risk, underscore the need
      to prioritize HIV risk and prevention initiatives for BHM.  We highlighted the
      structural contexts of HIV risk for BHM, and four community-based approaches to
      address HIV risk and prevention for BHM: (1) men's health programs; (2) workforce
      and postincarceration release programs; (3) linkages to women's prevention
      programs; and (4) faith-based initiatives.

PMID- 22401514
TI  - Improving firearm storage in Alaska native villages: a randomized trial of
      household gun cabinets.
AB  - OBJECTIVES: We determined if the installation of gun cabinets improved household
      firearm storage practices. METHODS: We used a wait list, randomized trial design
      with 2 groups. The "early" group received the intervention at baseline, and the
      "late" group received it at 12 months. Up to 2 gun cabinets were installed in
      each enrolled home, along with safety messages. In-person surveys were conducted
      at 12 and 18 months to determine the proportion of households reporting unlocked
      guns or ammunition. Direct observations of unlocked guns were also compared.
      RESULTS: At baseline, 93% of homes reported having at least 1 unlocked gun in the
      home, and 89% reported unlocked ammunition. At 12 months, 35% of homes in the
      early group reported unlocked guns compared with 89% in the late group (P <
      .001). Thirty-six percent of the early homes reported unlocked ammunition
      compared with 84% of late homes (P < .001). The prevalence of these storage
      practices was maintained at 18 months. Observations of unlocked guns decreased
      significantly (from 20% to 8%) between groups (P < .03). CONCLUSIONS: Gun cabinet
      installation in rural Alaskan households improved the storage of guns and
      ammunition. If these gains are sustained over time, it may lead to a reduction in
      gun-related injuries and deaths in this population.

PMID- 22401515
TI  - Taking it like a man: masculine role norms as moderators of the racial
      discrimination-depressive symptoms association among African American men.
AB  - OBJECTIVES: I examined the association between everyday racial discrimination and
      depressive symptoms and explored the moderating role of 2 dimensions of masculine
      role norms, restrictive emotionality and self-reliance. METHODS: Cross-sectional
      survey data from 674 African American men aged 18 years and older recruited
      primarily from barbershops in 4 US regions (2003-2010) were used. Direct and
      moderated associations were assessed with multivariate linear regression analyses
      for the overall sample and different age groups. Models were adjusted for
      recruitment site, sociodemographics, masculine role norms salience, and general
      social stress. RESULTS: Everyday racial discrimination was associated with more
      depressive symptoms across all age groups. Higher restrictive emotionality was
      associated with more depressive symptoms among men aged 18 to 29 and 30 to 39
      years. Self-reliance was associated with fewer depressive symptoms among men aged
      18 to 29 years and 40 years and older. The positive association between everyday
      racial discrimination and depressive symptoms was stronger among men with high
      restrictive emotionality, but this moderated effect was limited to men older than
      30 years. CONCLUSIONS: Interventions designed to reduce African American men's
      depression instigated by racism should be life-course specific and address
      masculine role norms that encourage emotion restriction.

PMID- 22401516
TI  - Modeling the impact of social discrimination and financial hardship on the sexual
      risk of HIV among Latino and Black men who have sex with men.
AB  - OBJECTIVES: We examined the impact of social discrimination and financial
      hardship on unprotected anal intercourse with a male sex partner of
      serodiscordant or unknown HIV status in the past 3 months among 1081 Latino and
      1154 Black men who have sex with men (MSM; n = 2235) residing in Los Angeles
      County, California; New York, New York; and Philadelphia, Pennsylvania. METHODS:
      We administered HIV testing and a questionnaire assessing 6 explanatory
      variables. We combined traditional mediation analysis with the results of a path
      analysis to simultaneously examine the direct, indirect, and total effects of
      these variables on the outcome variable. RESULTS: Bivariate analysis showed that
      homophobia, racism, financial hardship, and lack of social support were
      associated with unprotected anal intercourse with a serodiscordant or sero
      unknown partner. Path analysis determined that these relations were mediated by
      participation in risky sexual situations and lack of social support. However,
      paths between the explanatory variable and 2 mediating variables varied by
      participants' serostatus. CONCLUSIONS: Future prevention research and program
      designs should specifically address the differential impact of social
      discrimination and financial hardship on lack of social support and risky sexual
      situations among Latino and Black MSM.

PMID- 22401517
TI  - Health disparities in boys and men of color.

PMID- 22401518
TI  - Ethnic differences in mental illness and mental health service use among Black
      fathers.
AB  - OBJECTIVES: We have presented nationally representative data on the prevalence
      and correlates of mental illness and mental health service use among African
      American and Caribbean Black (US-born and foreign-born) fathers in the United
      States. METHODS: We have reported national estimates of lifetime and 12-month
      prevalence rates of mental illness, correlates, and service use among African
      American (n = 1254) and Caribbean Black (n = 633) fathers using data from the
      National Survey of American Life, a national household survey of Black Americans.
      We used bivariate cross-tabulations and Cox proportional hazards regression
      approaches and adjusted for the National Survey of American Life's complex sample
      design. RESULTS: The prevalence of mental illness, sociodemographic correlates,
      and service use among Black fathers varied by ethnicity and nativity. US-born
      Caribbean Black fathers had alarmingly high rates of most disorders, including
      depression, anxiety, and substance disorders. Mental health service use was
      particularly low for African American and foreign-born Caribbean Black fathers.
      CONCLUSIONS: These results demonstrate the need for more research on the causes
      and consequences of mental illness and the help-seeking behavior of ethnically
      diverse Black fathers.

PMID- 22401519
TI  - Measuring masculinity in research on men of color: findings and future
      directions.
AB  - The purpose of this study was to examine the association between masculinity and
      the health of US men of color aged 18 years and older. We identified 22
      population-based studies that included a measure of masculinity and a measure of
      health behavior, mental health, or physical health. The associations between
      masculinity and health were complex and varied by construct and health outcome,
      though they generally were significant in the hypothesized directions. Future
      research should explore the centrality of masculinity versus other identities and
      characteristics, how the relationship between masculinity and health varies by
      health outcome, and the identification of the conceptions and aspects of
      masculinity that are most relevant to and associated with specific health
      behaviors and health outcomes.

PMID- 22401522
TI  - Newly identified HIV infections in correctional facilities, United States, 2007.
AB  - We used Centers for Disease Control and Prevention HIV Counseling and Testing
      System data from 2007 to determine the percentage and characteristics of persons
      newly identified as HIV-positive in US correctional facilities. The newly
      identified HIV positivity was 0.7%, and 30% of detainees newly identified with
      HIV were categorized as having low-risk heterosexual contact or no acknowledged
      risk. Correctional facilities should provide detainees with routine opt-out HIV
      testing, unless the prevalence of previously undiagnosed HIV infection has been
      documented to be less than 0.1%.

PMID- 22401520
TI  - Work safety climate, musculoskeletal discomfort, working while injured, and
      depression among migrant farmworkers in North Carolina.
AB  - OBJECTIVES: This analysis described Latino migrant farmworkers' work safety
      climate and its association with musculoskeletal discomfort, working while
      injured or ill, and depressive symptoms. METHODS: Data were from a cross
      sectional survey of 300 farmworkers conducted in North Carolina in 2009.
      Generalized estimating equations models were used to investigate the association
      of work safety climate with health and safety outcomes. RESULTS: Farmworkers
      perceived their work safety climate to be poor. About 40% had elevated
      musculoskeletal discomfort, 5.0% had worked at least 1 day while injured or ill,
      and 27.9% had elevated depressive symptoms. The odds of elevated musculoskeletal
      discomfort were 12% lower and the odds of working while injured or ill were 15%
      lower with each 1-unit increase in the work safety climate. Work safety climate
      was not associated with depressive symptoms. CONCLUSIONS: Work safety climate was
      important for agricultural workers. Poor work safety climate was associated with
      health outcomes (musculoskeletal discomfort) and safety (working while injured or
      ill). Interventions to improve work safety climate in agriculture are needed,
      with these interventions being directed to employers and workers.

PMID- 22401523
TI  - Regarding the effect of physical activity on mortality.

PMID- 22401524
TI  - Rapid HIV testing in large urban jails.
AB  - HIV prevalence is higher in jails than in the community, yet many jails do not
      conduct HIV testing. Jails in Baltimore, Maryland; Philadelphia, Pennsylvania;
      and the District of Columbia have implemented innovative rapid HIV testing
      programs. We have summarized the results of these programs, including the numbers
      of persons tested, rapid and confirmatory HIV test results, and numbers of
      persons newly diagnosed with HIV. We have described facilitators and challenges
      of implementation. These programs confirmed that rapid HIV testing in jails was
      feasible and identified undiagnosed HIV infection. Challenges included limited
      space to provide confidential rapid HIV testing and rapid turnover of detainees.
      Implementation required collaboration between local governments, health agencies,
      and correctional institutions. These programs serve as models for expanding rapid
      HIV testing in jails.

PMID- 22401525
TI  - Social media and suicide: a public health perspective.
AB  - There is increasing evidence that the Internet and social media can influence
      suicide-related behavior. Important questions are whether this influence poses a
      significant risk to the public and how public health approaches might be used to
      address the issue. To address these questions, we provide an overview of ways
      that social media can influence suicidal behavior, both negatively and
      positively, and we evaluate the evidence of the risk. We also discuss the legal
      complexities of this important topic and propose future directions for research
      and prevention programs based on a public health perspective.

PMID- 22401526
TI  - Potential determinants of coal workers' pneumoconiosis, advanced pneumoconiosis,
      and progressive massive fibrosis among underground coal miners in the United
      States, 2005-2009.
AB  - OBJECTIVES: We better defined the distribution and determinants of coal workers'
      pneumoconiosis (CWP) among US underground coal miners. METHODS: We obtained chest
      radiographs from the mobile unit of an enhanced surveillance program begun in
      2005 by the National Institute for Occupational Safety and Health for underground
      coal miners. B Readers classified them for presence of pneumoconiosis. RESULTS:
      Miners from 15 states participated (n = 6658). The prevalence of CWP was higher
      in 3 states (Kentucky, 9.0%; Virginia, 8.0%; West Virginia, 4.8%) than in 12
      other states (age-adjusted risk ratio [RR] = 4.5; 95% confidence interval [CI] =
      3.3, 6.1). Miners in these 3 states were younger and had less mining tenure, but
      advanced CWP (category >= 2/1; RR = 8.1; 95% CI = 3.9, 16.9) and progressive
      massive fibrosis (RR = 10.5; 95% CI = 3.8, 29.1) was more prevalent among them.
      Advanced CWP and progressive massive fibrosis were more prevalent among workers
      at mines with fewer than 155 miners, irrespective of mining region, than among
      workers at larger mines. CONCLUSIONS: Enhanced surveillance results confirmed the
      persistence of severe CWP among US coal miners and documented the health
      consequences of inadequate dust control for miners in parts of Appalachia and at
      smaller mines.

PMID- 22401527
TI  - Health disparities in boys and men.

PMID- 22401528
TI  - End of the spectacular decrease in fall-related mortality rate: men are catching
      up.
AB  - OBJECTIVES: We determined time trends in numbers and rates of fall-related
      mortality in an aging population, for men and women. METHODS: We performed
      secular trend analysis of fall-related deaths in the older Dutch population
      (persons aged 65 years or older) from 1969 to 2008, using the national Official
      Cause-of-Death-Statistics. RESULTS: Between 1969 and 2008, the age-adjusted fall
      related mortality rate decreased from 202.1 to 66.7 per 100,000 older persons
      (decrease of 67%). However, the annual percentage change (change per year) in
      mortality rates was not constant, and could be divided into 3 phases: (1) a rapid
      decrease until the mid-1980s (men -4.1%; 95% confidence interval [CI] = -4.9, 
      3.2; women -6.5%; 95% CI, -7.1, -5.9), (2) flattening of the decrease until the
      mid-1990s (men -1.4%; 95% CI = -2.4, -0.4; women -2.0%; 95% CI = -3.4, -0.6), and
      (3) stable mortality rates for women (0.0%; 95% CI = -1.2, 1.3) and rising rates
      for men (1.9%; 95% CI = 0.6, 3.2) over the last decade. CONCLUSIONS: The
      spectacular decrease in fall-related mortality ended in the mid-1990s and is
      currently increasing in older men at similar rates to those seen in women.
      Because of the aging society, absolute numbers in fall-related deaths are
      increasing rapidly.

PMID- 22401529
TI  - Wicasa Was'aka: restoring the traditional strength of American Indian boys and
      men.
AB  - We examined health disparities among American Indian men and boys within the
      framework of historical trauma, which incorporates the historical context of
      collective massive group trauma across generations. We reviewed the impact of
      collective traumatic experiences among Lakota men, who have faced cross
      generational challenges to enacting traditional tribal roles.  We describe
      historical trauma-informed interventions used with two tribal groups: Lakota men
      and Southwestern American Indian boys. These two interventions represent novel
      approaches to addressing historical trauma and the health disparities that
      American Indians face.  We offer public health implications and recommendations
      for strategies to use in the planning and implementation of policy, research, and
      program development with American Indian boys and men.

PMID- 22401531
TI  - Oral health-related quality-of-life in patients to be treated with fixed or
      removable partial dental prostheses.
AB  - OBJECTIVES: The aims of this study were to measure and describe the Oral Health
      Related Quality-of-Life (OHRQoL) in a population about to receive removable
      dental prostheses (RDP) or fixed dental prostheses (FDP). MATERIALS AND METHODS:
      The Oral Health Impact Profile 49 (OHIP-49) was completed by 410 patients about
      to receive treatment with either RDP or FDP. Objective variables were: gender,
      age, number of teeth, type of replacement planned (FDP/RDP) and location (one jaw
      or both) and zone (aesthetic/masticatory/both) of missing teeth to be replaced.
      RESULTS: Women had a worse OHRQoL than men in the RDP group. Higher age was
      significantly correlated with a better OHRQoL independent of treatment modality.
      Participants about to receive FDP in one jaw in the masticatory zone only had a
      better OHRQoL than RDP participants in the same group. The most frequently
      reported problems in all groups concerned functional limitations, discomfort and
      physical disabilities. Little variance in reported items was seen between the sub
      groups and social handicap was not frequently reported. CONCLUSIONS: The
      difference in OHRQoL between participants about to receive RDP and FDP was
      limited. The most frequently reported problems concerned functional limitations,
      discomfort and physical disabilities. Social handicap was not frequently
      reported.

PMID- 22401530
TI  - Childhood maltreatment histories, alcohol and other drug use symptoms, and sexual
      risk behavior in a treatment sample of adolescents.
AB  - OBJECTIVES: We tested a structural model of relations among self-reported
      childhood maltreatment, alcohol and other drug abuse and dependence symptoms, and
      sexual risk behavior in a sample of adolescents receiving outpatient treatment of
      substance use problems. METHODS: Structured interviews were administered to an
      ethnically diverse sample of 394 adolescents (114 girls, 280 boys; mean = 16.30
      years; SD = 1.15 years; 44.9% Hispanic, 20.6% African American, 25.4% White non
      Hispanic, and 9.1% other) in 2 outpatient treatment settings. RESULTS: Path
      analyses yielded findings consistent with a mediation model. Alcohol abuse and
      dependence symptoms mediated (1) relations between emotional neglect scores and
      sex with co-occurring alcohol use and (2) relations between sexual abuse scores
      and sex with co-occurring alcohol use. Drug abuse and dependence symptoms
      mediated relations between (1) neglect scores and (2) sexual intercourse with co
      occurring alcohol or drug use, as well as unprotected sexual intercourse.
      CONCLUSIONS: Efforts to treat alcohol or drug use problems among adolescents or
      to prevent transmission of HIV or other sexually transmitted infections among
      youths with substance use problems may require tailoring treatment or prevention
      protocols to address client histories of maltreatment.

PMID- 22401532
TI  - Nonionic surfactant and interfacial structure impact crystallinity and stability
      of beta-carotene loaded lipid nanodispersions.
AB  - The stability, crystallization, and melting behavior of canola stearin (CaSt)
      solid lipid nanoparticle dispersions (SLN) and canola oil-in-water emulsions
      (COE) with 10 wt % Poloxamer 188 (P188) or Tween 20 (T20) with and without 0.1 wt
      % beta-carotene (BC) were investigated. Particles or droplets with diameters in
      the range of 115 nm were formed and stable for up to 90 days at 4 or 20  degrees
      C. Polymorphism was affected by surfactant type; that is, only beta versus both
      beta' and beta were observed for the P188 and T20 SLN, respectively. According to
      Cryo-TEM, the emulsions and SLN were spherical versus platelet-like structures,
      respectively, with differences observed between SLN with P188 or T20. More
      surfactant was interfacially adsorbed in the SLN versus COE. Incorporation of BC
      at 0.1 wt % had no impact on SLN or COE size, polymorphism, or melting behavior.
      Less BC degradation was observed for the SLN versus COE and during storage at 4
      versus 20  degrees C (p < 0.05).

PMID- 22401533
TI  - Aromatic pathways of porphins, chlorins, and bacteriochlorins.
AB  - Magnetically induced current densities have been calculated for free-base
      porphynoids using the gauge including magnetically induce current (GIMIC) method.
      Numerical integration of the current density passing selected chemical bonds
      yields current pathways and the degree of aromaticity according to the magnetic
      criterion. The ring-current strengths of the porphins, chlorins, and
      bacteriochlorins are 1.5-2.5 times stronger than for benzene. The calculations
      show that the 18pi [16]annulene inner cross is not the correct picture of the
      aromatic pathway for porphyrins. All conjugated chemical bonds participate in the
      current transport independently of the formal number of pi electrons. The ring
      current branches at the pyrrolic rings taking both the outer and the inner route.
      The NH unit of the pyrrolic rings has a larger resistance and a weaker current
      strength than the pyrroles without inner hydrogens. The traditional 18pi
      [18]annulene with inactive NH bridges is not how the ring-current flows around
      the macroring. The porphins have the strongest ring current of ca. 27 nA/T among
      the investigated porphynoids. The current strengths of the chlorins and
      bacteriochlorins are 19-24 nA/T depending on whether the ring current is forced
      to pass an NH unit or not. The current strengths of the 3-fold and 4-fold beta
      saturated porphynoids are 13-17 nA/T, showing that the inner-cross 18pi
      [16]annulene pathway is not a preferred current route.

PMID- 22401534
TI  - Increasing organ donation via anticipated regret (INORDAR): protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Throughout the world there is an insufficient supply of donor organs
      to meet the demand for organ transplantations. This paper presents a protocol for
      a randomised controlled trial, testing whether a simple, theory-based anticipated
      regret manipulation leads to a significant increase in posthumous organ donor
      registrations. METHODS: We will use a between-groups, prospective randomised
      controlled design. A random sample of 14,520 members of the adult Scottish
      general public will be contacted via post. These participants will be randomly
      allocated into 1 of the 4 conditions. The no questionnaire control (NQC) group
      will simply receive a letter and donor registration form. The questionnaire
      control (QC) arm will receive a questionnaire measuring their emotions and non
      cognitive affective attitudes towards organ donation. The theory of planned
      behavior (TPB) group will complete the emotions and affective attitudes
      questionnaire plus additional items assessing their cognitive attitudes towards
      organ donation, perceived control over registration and how they think
      significant others view this action. Finally, the anticipated regret (AR) group
      will complete the same indices as the TPB group, plus two additional anticipated
      regret items. These items will assess the extent to which the participant
      anticipates regret for not registering as an organ donor in the near future. The
      outcome variable will be NHS Blood and Transplant verified registrations as an
      organ donor within 6 months of receiving our postal intervention. DISCUSSION:
      This study will assess whether simply asking people to reflect on the extent to
      which they may anticipate regret for not registering as an organ donor increases
      organ donor registration 6 months later. If successful, this simple and easy to
      administer theory-based intervention has the potential to save lives and money
      for the NHS by reducing the number of people receiving treatments such as
      dialysis. This intervention may also be incorporated into future organ donor
      campaigns. TRIAL REGISTRATION NUMBER: ISRCTN: ISRCTN92204897.

PMID- 22401535
TI  - Temporal, seasonal and weather effects on cycle volume: an ecological study.
AB  - BACKGROUND: Cycling has the potential to provide health, environmental and
      economic benefits but the level of cycling is very low in New Zealand and many
      other countries. Adverse weather is often cited as a reason why people do not
      cycle. This study investigated temporal and seasonal variability in cycle volume
      and its association with weather in Auckland, New Zealand's largest city.
      METHODS: Two datasets were used: automated cycle count data collected on Tamaki
      Drive in Auckland by using ZELT Inductive Loop Eco-counters and weather data
      (gust speed, rain, temperature, sunshine duration) available online from the
      National Climate Database. Analyses were undertaken using data collected over one
      year (1 January to 31 December 2009). Normalised cycle volumes were used in
      correlation and regression analyses to accommodate differences by hour of the day
      and day of the week and holiday. RESULTS: In 2009, 220,043 bicycles were recorded
      at the site. There were significant differences in mean hourly cycle volumes by
      hour of the day, day type and month of the year (p < 0.0001). All weather
      variables significantly influenced hourly and daily cycle volumes (p < 0.0001).
      The cycle volume increased by 3.2% (hourly) and 2.6% (daily) for 1 degrees C
      increase in temperature but decreased by 10.6% (hourly) and 1.5% (daily) for 1 mm
      increase in rainfall and by 1.4% (hourly) and 0.9% (daily) for 1 km/h increase in
      gust speed. The volume was 26.2% higher in an hour with sunshine compared with no
      sunshine, and increased by 2.5% for one hour increase in sunshine each day.
      CONCLUSIONS: There are temporal and seasonal variations in cycle volume in
      Auckland and weather significantly influences hour-to-hour and day-to-day
      variations in cycle volume. Our findings will help inform future cycling
      promotion activities in Auckland.

PMID- 22401536
TI  - Starfruit-shaped gold nanorods and nanowires: synthesis and SERS
      characterization.
AB  - Recently, branched and star-shaped gold nanoparticles have received significant
      attention for their unique optical and electronic properties, but most examples
      of such nanoparticles have a zero-dimensional shape with varying numbers of
      branches coming from a quasi-spherical core. This report details the first
      examples of higher-order penta-branched gold particles including rod-, wire-, and
      platelike particles which contain a uniquely periodic starfruitlike morphology.
      These nanoparticles are synthesized in the presence of silver ions by a seed
      mediated approach based on utilizing highly purified pentahedrally twinned gold
      nanorods and nanowires as seed particles. The extent of the growth can be varied,
      leading to shifts in the plasmon resonances of the particles. In addition, the
      application of the starfruit rods for surface-enhanced Raman spectroscopy (SERS)
      is demonstrated.

PMID- 22401537
TI  - Rituximab effectively reduces macrophage migration inhibitory factor in patients
      with active rheumatoid arthritis.

PMID- 22401538
TI  - Patients with worsening chronic heart failure who present to a hospital emergency
      department require hospital care.
AB  - BACKGROUND: Chronic heart failure (CHF) is a major public health problem
      characterised by progressive deterioration with disabling symptoms and frequent
      hospital admissions. To influence hospitalisation rates it is crucial to identify
      precipitating factors.To characterise patients with CHF who seek an emergency
      department (ED) because of worsening symptoms and signs and to explore the
      reasons why they are admitted to hospital. METHOD: Patients (n = 2,648) seeking
      care for dyspnoea were identified at the ED, Sahlgrenska University
      Hospital/Ostra. Out of 2,648 patients, 1,127 had a previous diagnosis of CHF, and
      of these, 786 were included in the present study with at least one sign and one
      symptom of worsening CHF. RESULTS: Although several of the patients wanted to go
      home after acute treatment in the ED, only 2% could be sent home. These patients
      were enrolled in an interventional study, which evaluated the acute care at home
      compared to the conventional, in hospital care. The remaining patients were
      admitted to hospital because of serious condition, including
      pneumonia/respiratory disease, myocardial infarction, pulmonary oedema, anaemia,
      the need to monitor cardiac rhythm, pathological blood chemistry and difficulties
      to communicate. CONCLUSION: The vast majority of patients with worsening CHF
      seeking the ED required hospital care, predominantly because of co-morbidities.
      Patients with CHF with symptomatic deterioration may be admitted to hospital
      without additional emergency room investigations.

PMID- 22401539
TI  - Celebrating the modern lab.

PMID- 22401542
TI  - Definitive answers. Interview by Kristie Nybo.

PMID- 22401543
TI  - Microfluidics, macro-impacts.

PMID- 22401544
TI  - 5' RACE.

PMID- 22401545
TI  - Run your lab on dollars a day!

PMID- 22401546
TI  - Reflections on the modern lab.

PMID- 22401547
TI  - Construction of "small-intelligent" focused mutagenesis libraries using well
      designed combinatorial degenerate primers.
AB  - Site-saturation mutagenesis is a powerful tool for protein optimization due to
      its efficiency and simplicity. A degenerate codon NNN or NNS (K) is often used to
      encode the 20 standard amino acids, but this will produce redundant codons and
      cause uneven distribution of amino acids in the constructed library. Here we
      present a novel "small-intelligent" strategy to construct mutagenesis libraries
      that have a minimal gene library size without inherent amino acid biases, stop
      codons, or rare codons of Escherichia coli by coupling well-designed
      combinatorial degenerate primers with suitable PCR-based mutagenesis methods. The
      designed primer mixture contains exactly one codon per amino acid and thus allows
      the construction of small-intelligent mutagenesis libraries with one gene per
      protein. In addition, the software tool DC-Analyzer was developed to assist in
      primer design according to the user-defined randomization scheme for library
      construction. This small-intelligent strategy was successfully applied to the
      randomization of halohydrin dehalogenases with one or two randomized sites. With
      the help of DC-Analyzer, the strategy was proven to be as simple as NNS
      randomization and could serve as a general tool to efficiently randomize target
      genes at positions of interest.

PMID- 22401548
TI  - U-2012: An improved Lowry protein assay, insensitive to sample color, offering
      reagent stability and enhanced sensitivity.
AB  - Traditional colorimetric protein assays such as Biuret, Lowry, and modified Lowry
      (U-1988) are unsuitable for colored biological samples. Here we describe an
      improved Lowry protein assay (U-2012), which utilizes stable reagents and offers
      enhanced sensitivity over the U-1988 assay. U-2012 circumvents interference from
      colored pigments and other substances (for example sugars) bound to perchloric
      acid (PCA) precipitated proteins by hydrogen peroxide (H2O2) induced oxidation at
      50 degrees C. Unused hydrogen peroxide is neutralized with sodium pyruvate before
      protein estimation for a stable end color. The U-2012 assay is carried out on the
      PCA precipitated protein pellet after neutralization (with Na2CO3 plus NaOH),
      solubilization (in Triton-NaCl), decolorization (by H2O2) and pyruvate treatment.
      Protein contents in red wine and homogenates of beetroot and blueberry are
      calculated from standard curves established for various proteins and generated
      using a rectangular hyperbola with parameters estimated with Microsoft Excel's
      Solver add-in. The U-2012 protein assay represents an improvement over U-1988 and
      gives a more accurate estimation of protein content.

PMID- 22401549
TI  - Small RNA fragments in complex culture media cause alterations in protein
      profiles of three species of bacteria.
AB  - Efforts to delineate the basis for variations in protein profiles of different
      membrane fractions from various bacterial pathogens led to the finding that even
      the same medium [e.g., Luria Bertani (LB) broth] purchased from different
      commercial sources generates remarkably dissimilar protein profiles despite
      similar growth characteristics. Given the pervasive roles small RNAs play in
      regulating gene expression, we inquired if these source-specific differences due
      to media arise from disparities in the presence of small RNAs. Indeed, LB media
      components from two different commercial suppliers contained varying, yet
      significant, amounts of 10-80 bp small RNAs. Removal of small RNA from LB using
      RNaseA during media preparation resulted in significant changes in bacterial
      protein expression profiles. Our studies underscore the fact that seemingly
      identical growth media can lead to dramatic alterations in protein expression
      patterns, highlighting the importance of utilizing media free of small RNA during
      bacteriological studies. Finally, these results raise the intriguing possibility
      that similar pools of small RNAs in the environment can influence bacterial
      adaptation.

PMID- 22401550
TI  - Construction of a bicistronic vector for the co-expression of two genes in
      Caenorhabditis elegans using a newly identified IRES.
AB  - The nematode Caenorhabditis elegans is an important model animal for biological
      research. Currently, transgenic C. elegans strains are mainly generated by
      injecting DNA encoding a gene of interest, in combination with a reporter gene,
      into the gonad. With this approach, the interpretation of negative results, such
      as the failure to observe reporter expression, is frequently required. Single,
      selectable vectors are urgently required. Internal ribosome entry site (IRES)
      elements are known to bind the eukaryotic ribosomal translation initiation
      complex and independently promote translation initiation. Bioinformatic analysis
      predicted an IRES motif upstream of the start codon of the C. elegans Hsp-3 gene.
      While this sequence has a Y-shaped double-hairpin secondary structure
      characteristic of IRES elements, it was unclear if it could function as an IRES.
      In the present study, this predicted Hsp-3 IRES was incorporated into a
      bicistronic vector driven by the myo-3 promoter, which allowed co-expression of
      RFP and GFP genes in the muscle tissue of C. elegans and thereby demonstrated
      that this IRES element is functional. This vector provides a novel, powerful tool
      for C. elegans research.

PMID- 22401551
TI  - Stimulation with a low-amplitude, digitized synaptic signal to invoke robust
      activity within neuronal networks on multielectrode arrays.
AB  - Multielectrode arrays (MEAs) are used for analysis of neuronal activity. Here we
      report two variations on commonly accepted techniques that increase the precision
      of extracellular electrical stimulation: (i) the use of a low-amplitude recorded
      spontaneous synaptic signal as a stimulus waveform and (ii) the use of a specific
      electrode within the array adjacent to the stimulus electrode as a hard-grounded
      stimulus signal return path. Both modifications remained compatible with
      manipulation of neuronal networks. In addition, localized stimulation with the
      low-amplitude synaptic signal allowed selective stimulation or inhibition of
      otherwise spontaneous signals. These findings indicate that minimizing the area
      of the culture impacted by external stimulation allows modulation of signaling
      patterns within subpopulations of neurons in culture. The simple modifications
      described herein may be useful for precise monitoring and manipulation of
      neuronal networks.

PMID- 22401552
TI  - High-throughput genotyping of advanced congenic lines by high resolution melting
      analysis for identification of Bbaa2, a QTL controlling Lyme arthritis.
AB  - Congenic mapping is a powerful strategy to identify genomic loci regulating
      quantitative traits. Generating congenic lines is an iterative process of
      refinement that is both time and resource intensive. Here we report an
      alternative to traditional microsatellite marker analysis or costly high-density
      oligonucleotide single nucleotide polymorphism (SNP) arrays for congenic
      genotyping. The identification of inherited SNP variability in congenic lines
      using high resolution melting analysis (HRMA) represents a novel application of
      the method. The blocked probe HRMA approach offers a scalable, low cost, closed
      tube system that benefits from rapid turnaround times, and unequivocal
      interpretation. The markedly higher prevalence of SNPs relative to
      microsatellites in the genome allows much greater flexibility for the
      identification of new genotyping landmarks as congenic intervals are refined. We
      have adopted this approach in our development of B6.C3-Bbaa2 congenic lines for
      the identification of loci regulating murine Lyme arthritis severity. As a
      result, we have been able to fully genotype individuals prior to weaning age, and
      expand our number of breeding cages without increasing our colony budget. Thus
      far, 26 SNP markers have been successfully mapped to the Bbaa2 locus. This has
      facilitated the identification of 20 novel B6.C3-Bbaa2 congenic lines spanning
      the original interval.

PMID- 22401557
TI  - Core/shell nanofibers with embedded liposomes as a drug delivery system.
AB  - The broader application of liposomes in regenerative medicine is hampered by
      their short half-life and inefficient retention at the site of application. These
      disadvantages could be significantly reduced by their combination with
      nanofibers. We produced 2 different nanofiber-liposome systems in the present
      study, that is, liposomes blended within nanofibers and core/shell nanofibers
      with embedded liposomes. Herein, we demonstrate that blend electrospinning does
      not conserve intact liposomes. In contrast, coaxial electrospinning enables the
      incorporation of liposomes into nanofibers. We report polyvinyl alcohol-core/poly
      epsilon-caprolactone-shell nanofibers with embedded liposomes and show that they
      preserve the enzymatic activity of encapsulated horseradish peroxidase. The
      potential of this system was also demonstrated by the enhancement of mesenchymal
      stem cell proliferation. In conclusion, intact liposomes incorporated into
      nanofibers by coaxial electrospinning are very promising as a drug delivery
      system.

PMID- 22401558
TI  - Stem cells and regenerative medicine - future perspectives.
AB  - Stem cell research has expanded at an exponential rate, but its therapeutic
      applications have progressed much more slowly. Currently, the research focuses on
      understanding embryonic, adult, and inducible pluripotent stem cells. Translation
      of adult stem cell research has established a definitive benefit that is greater
      than that of the current standard of care in the field of cardiovascular
      medicine. The future of stem cell research and therapy will continue to provide
      novel avenues of diagnostics, therapeutics, and tissue regeneration. Here we
      discuss a brief history of stem cell research as it transitioned from the 20th to
      the 21st century. We address lessons learned in the first decade of the new
      millennium that could help guide others to translate research into therapy across
      disciplines. Finally, we highlight future goals and challenges that must be
      overcome and offer some perspective on the bright future of stem cell research
      and therapy.

PMID- 22401559
TI  - Liquid crystalline phases induced by the hydroxyl group stereochemistry of
      amphiphilic carbohydrate bicatenary derivatives.
AB  - Liquid crystals (LCs) may exist in different phases depending upon the
      orientational and positional orders of molecules in the material. Here, we
      demonstrate that the class of LC state induced by amphiphilic carbohydrate
      bicatenary derivatives is strictly hydroxyl group stereochemistry-dependent. This
      statement results from the experimental and theoretical investigations of surface
      film (2D) and bulk solid (3D) thermal behavior of synthetic stereoisomers n
      tetradecyl (alpha-D-n-tetradecyl) galacto- and gluco-pyranosiduronate, with an
      axial (GalA-C(14/14)) or equatorial (GlcA-C(14/14)) hydroxyl group at the fourth
      carbon, respectively. Surface pressure-area isotherms (283-310 K), differential
      scanning calorimetry thermograms (223-573 K), and polarized optical textures (298
      363 K) reveal that GlcA-C(14/14) organizes as a smectic LC-like phase (positional
      or lateral order), whereas the analogous stereoisomer GalA-C(14/14) behaves as a
      nematic LC-like phase (orientational order). Thermodynamic investigations and
      molecular dynamics models computed under similar temperature conditions provide
      consistent data with physical properties resulting from experimental approaches.

PMID- 22401560
TI  - Detection methodology based on target molecule-induced sequence-specific binding
      to a single-stranded oligonucleotide.
AB  - We have recently developed a mix-and-read format homogeneous antigen peptide
      based assay for detection of the antibodies (Tian, L.; Heyduk, T. Anal. Chem.
      2009, 81, 5218-5225) that employed for target detection a simple biophysical
      mechanism of target antibody induced annealing between two complementary
      oligonucleotides attached to the antigen peptide. In this work, we propose and
      experimentally validate an alternative variant of this assay format in which
      target antibody binding to antigen peptide-oligonucleotide conjugate produces a
      complex with high sequence-specific binding affinity to a single-stranded capture
      oligonucleotide. This new assay format can be used for preparing various solid
      surface based assays by immobilizing the capture oligonucleotide. This assay
      design is not limited to antibody detection. We demonstrate that it can also be
      employed for detecting proteins or pathogenic bacteria using oligonucleotide
      labeled antibodies as target recognition elements. Preparation of these solid
      surface based assays is simplified because all interactions with the solid
      surfaces are mediated by well-understood oligonucleotide-oligonucleotide
      interactions and because of the relative ease of immobilizing oligonucleotides on
      various solid surfaces. These unique aspects of the assay design also allow
      microarray-style multiplexing that could be most useful for multiplexed antibody
      profiling for diagnosis and analysis of cancer, autoimmune, and infectious
      diseases.

PMID- 22401561
TI  - In vitro dissolution and in vivo absorption of calcium [1-(14)c]butyrate in free
      or protected forms.
AB  - Butyrate is a byproduct of microbial carbohydrate fermentation that occurs
      primarily in the large intestine. When added to feed, butyrate quickly disappears
      in the upper digestive tract. Because butyrate is important for epithelial cell
      development, mucosal integrity, and animal growth, an encapsulation technique has
      been developed that allows for the slow release of butyrate into the small and
      large intestines. The purpose of this study was to describe the in vitro release
      of calcium [1-(14)C]butyrate, formulated into a slow-release (protected) bead,
      into water and simulated intestinal fluids and to compare the in vivo absorption
      and disposition of unprotected versus protected calcium [1-(14)C]butyrate in
      broiler chicks. Formulation of calcium [1-(14)C]butyrate into protected beads
      allowed release of 5.8 +/- 0.2 and 3.4 +/- 0.2% of the formulated radiocarbon
      into water and gastric fluid, respectively, after 2 h of incubation. Beads
      incubated in gastric fluid for 2 h and subsequently incubated in simulated
      intestinal fluid released a total of 17.4 +/- 0.8% of the formulated
      radioactivity. Release of respiratory [(14)C]CO(2) after oral dosing of aqueous
      calcium [1-(14)C]butyrate in broiler chicks peaked at 15.2 +/- 5.2% per hour 1.5
      h after dosing; in contrast, maximal rates of release in chicks dosed with
      protected calcium [1-(14)C]butyrate occurred 4 h after dosing at 9.0 +/- 3.1% per
      hour. The data suggested an improved efficacy of protected butyrate delivery to
      intestinal tissues over nonprotected butyrate. This study confirmed that
      encapsulation strategies designed to enhance delivery of ingredients to improve
      intestinal health are effective at prolonging intestinal exposure to butyrate.
      Encapsulation of such ingredients might benefit the food and feed industries.

PMID- 22401562
TI  - Identification of Neisseria gonorrhoeae isolates with a recombinant porA gene in
      Scotland, United Kingdom, 2010 to 2011.
AB  - Three isolates of Neisseria gonorrhoeae have been identified in Scotland in 2010
      and 2011, which lack sequences in the porA pseudogene commonly used as the target
      for confirmatory gonorrhoea polymerase chain reaction assays. Two isolates were
      clustered temporally and geographically and have the same sequence type and porA
      sequence. A similar strain was reported in Australia during early 2011. The other
      Scottish isolate was identified separately and is different in sequence type and
      porA sequence.

PMID- 22401563
TI  - Clinical Neisseria gonorrhoeae isolate with a N. meningitidis porA gene and no
      prolyliminopeptidase activity, Sweden, 2011: danger of false-negative genetic and
      culture diagnostic results.
AB  - We describe a Neisseria gonorrhoeae strain, found in Sweden in 2011, that
      harbours a N. meningitidis porA gene causing false-negative results in PCRs
      targeting the gonococcal porA pseudogene. Furthermore, the strain had no
      prolyliminopeptidase (PIP) activity that many commercial biochemical kits for
      species verification in culture rely on. Enhanced awareness of the spread of such
      strains and screening for them can be crucial.

PMID- 22401564
TI  - Overrepresentation of influenza A(H1N1)pdm09 virus among severe influenza cases
      in the 2011/12 season in four European countries.
AB  - In France, Ireland, Spain and the United Kingdom, the influenza season 2011/12
      started in the final weeks of 2011 and has been dominated by influenza A(H3)
      viruses with minimal circulation of influenza A(H1N1) pdm09 and B viruses. A
      relatively greater proportion, however, of influenza A(H1N1)pdm09 viruses were
      reported in hospitalised laboratory-confirmed influenza cases in four countries.
      Compared to the season 2010/11, the proportion of subtype A(H3) among
      hospitalised cases has increased, associated with a larger proportion of cases in
      the youngest and oldest age groups.

PMID- 22401565
TI  - Gastroenteritis outbreaks in elderly homes in the east of France during winter
      2009/10: aetiology research for a series of 37 outbreaks.
AB  - Although acute gastroenteritis is a common cause of morbi-mortality in care
      homes, there is no national surveillance system in France except for food-borne
      gastroenteritis. Since 2008, a specific surveillance system has been operating in
      nursing homes in Alsace, a region in eastern French. In the winter season 2009/10
      we had the opportunity to study 37 outbreaks, collecting data on attack rate,
      duration and aetiology as well as epidemic management in nursing homes. We
      noticed the responsiveness of the institutions, with a mean period of 1.6 days
      between the onset of first symptoms and the implementation of management measures
      (95% confidence interval (CI): 1.0-2.2). One or several stool samples were taken
      in 27 of the 37 described outbreaks. The only pathogen detected was norovirus,
      and the positive samples were from outbreaks with a very typical pattern:
      vomiting in 36 of the outbreaks, a high average attack rate of 36.8% (95% CI:
      31.5-42.2) and a short average duration of 8.9 days (95% CI: 5.8-7.0). No severe
      cases, hospitalisations or deaths were reported. The high frequency of norovirus
      isolation indicated that systematic bacteriological analysis in local
      laboratories is not cost-effective. Consequently, Cire Est recommends to test for
      bacteria and viruses only in cases presenting with fever or atypical symptoms.
      Nevertheless, Cire Est also recommends to continue sending stool samples to the
      French National Centre for enteric viruses, more for the benefit of the
      virological surveillance programme than for diagnostic purposes.

PMID- 22401566
TI  - A norovirus outbreak triggered by copper intoxication on a coach trip from the
      Netherlands to Germany, April 2010.
AB  - We report an unusual outbreak of norovirus infection on a coach trip. Overall, 30
      of 40 people (including drivers and crew) developed nausea, vomiting and/or
      diarrhoea, 11 of them on the first day of the trip. The incidence epidemic curve
      showed a first peak on Day 1 and a second on Day 4. Nine passengers were
      hospitalised with gastrointestinal symptoms. Norovirus was found in stool samples
      from two patients, but the infection could not explain the first peak in the
      epidemic curve only a few hours after departure. Interviews with the passengers
      and an inspection of the coach and its water supply implicated the water used for
      coffee and tea as the potential source. Microbiological investigations of the
      water were negative, but chemical analysis showed a toxic concentration of
      copper. Blood copper levels as well as renal and liver function were determined
      in 28 of the 32 passengers who had been exposed to the water. One passenger who
      did not have gastrointestinal symptoms had an elevated copper level of 25.9
      MUmol/L, without loss of liver or renal function. It is likely that the spread of
      norovirus was enhanced because of vomiting of one of the passengers due to copper
      intoxication.

PMID- 22401567
TI  - MutS homologue hMSH5: role in cisplatin-induced DNA damage response.
AB  - BACKGROUND: Cisplatin (cis-diamminedichloroplatinum (II), CDDP) and its analogues
      constitute an important class of anticancer drugs in the treatment of various
      malignancies; however, its effectiveness is frequently affected by mutations in
      genes involved in the repair and signaling of cisplatin-induced DNA damage. These
      observations necessitate a need for a better understanding of the molecular
      events governing cellular sensitivity to cisplatin. RESULTS: Here, we show that
      hMSH5 mediates sensitization to cisplatin-induced DNA damage in human cells. Our
      study indicates that hMSH5 undergoes cisplatin-elicited protein induction and
      tyrosine phosphorylation. Silencing of hMSH5 by RNAi or expression of hMSH5
      phosphorylation-resistant mutant hMSH5Y742F elevates cisplatin-induced G2 arrest
      and renders cells susceptible to cisplatin toxicity at clinically relevant doses.
      In addition, our data show that cisplatin promotes hMSH5 chromatin association
      and hMSH5 deficiency increases cisplatin-triggered gamma-H2AX foci. Consistent
      with a possible role for hMSH5 in recombinational repair of cisplatin-triggered
      double-strand breaks (DSBs), the formation of cisplatin-induced hMSH5 nuclear
      foci is hRad51-dependent. CONCLUSION: Collectively, our current study has
      suggested a role for hMSH5 in the processing of cisplatin-induced DSBs, and
      silencing of hMSH5 may provide a new means to improve the therapeutic efficacy of
      cisplatin.

PMID- 22401568
TI  - Application of the 2010 ACR/EULAR classification criteria for rheumatoid
      arthritis in Korean patients with undifferentiated arthritis.
AB  - OBJECTIVE: The aim of this study was to determine how many patients with
      undifferentiated arthritis (UA) are classified as patients with rheumatoid
      arthritis (RA) by the 2010 American College of Rheumatology/European League
      Against Rheumatism (ACR/EULAR) criteria for RA. METHODS: The 2010 ACR/EULAR
      criteria for RA were applied to 102 patients with UA. UA is defined as an
      inflammatory arthritis that does not meet any criteria for a definitive
      diagnosis. We analysed discrepancy in the classification between previous
      criteria and the 2010 criteria by identifying patients who were categorized as
      those with RA. RESULTS: The mean age of the patients was 46.8 +/- 14.3 years.
      Rheumatoid factor (RF) was positive in 36 patients (35.2%), and 30 patients
      (29.5%) were positive for anti-cyclic citrullinated peptide antibody (anti-CCP).
      The 2010 ACR/EULAR criteria classified 33 patients (32.4%) as having RA, and 31
      of them (93.9%) had the involvement of 1-3 small joints. All patients were
      seropositive, and 25 of them (75.8%) had high positive RF or anti-CCP.
      Seropositivity and small joint involvement was significantly different between
      patients who were classified with RA and those who were not (p < 0.001).
      CONCLUSION: Using the 2010 ACR/EULAR criteria, 32.4% of patients with UA were
      classified as having RA, and all were seropositive. Most of the UA patients with
      high positive RF or anti-CCP could be classified as having RA when we applied the
      2010 ACR/EULAR criteria.

PMID- 22401569
TI  - Structural and electrostatic asymmetry at the active site in typical and atypical
      peroxiredoxin dimers.
AB  - The peroxiredoxins (Prx) are ubiquitous peroxidases involved in important
      biological processes; however, details of their enzymatic mechanism remain
      elusive. To probe potential dynamics-function relationships, molecular dynamics
      simulations and electrostatic calculations were performed on the atypical 2
      cysteine thiol peroxidase (Tpx) from Streptococcus pneumoniae and results
      compared to a previous study of a typical 2-cysteine Prx from Trypanosoma cruzi.
      The analyses indicate a commonality between both typical and atypical Prx:
      dynamic asymmetry. Asymmetry is observed in structure, fluctuations, and active
      site electrostatics. Key residues, including Glu150 and Phe153, play roles in the
      developing asymmetry; furthermore, in the atypical 2-Cys Tpx, Glu150 exhibits
      conformation fluctuations suggesting involvement in a proton shuttle. The
      existence of a pathway of connected residues appears to propagate the asymmetry.
      The commonality of asymmetry and coupling pathways in both typical and atypical
      Prxs suggests a driving force toward dimer asymmetry as a common feature that
      plays a functional role in creating one active site with a lower cysteine pK(a).

PMID- 22401570
TI  - Rapid and highly sensitive method for influenza A (H1N1) virus detection.
AB  - In this study, we applied the developed paired surface plasma waves biosensor
      (PSPWB) in a dual-channel biosensor for rapid and sensitive detection of swine
      origin influenza A (H1N1) virus (S-OIV). In conjunction with the amplitude ratio
      of the signal and the reference channel, the stability of the PSPWB system is
      significantly improved experimentally. The theoretical limit of detection (LOD)
      of the dual-channel PSPWB for S-OIV is 30 PFU/mL (PFU, plaque-forming unit),
      which was calculated from the fitting curve of the surface plasmon resonance
      signal with a S-OIV clinical isolate concentration in phosphate-buffered saline
      (PBS) over a range of 18-1.8 * 10(6) PFU/mL. The LOD is 2 orders of magnitude
      more sensitive than the commercial rapid influenza diagnostic test at worst and
      an order of magnitude less sensitive than real-time quantitative polymerase chain
      reaction (PCR) whose LOD for S-OIV in PBS was determined to be 3.5 PFU/mL in this
      experiment. Furthermore, under in vivo conditions, this experiment demonstrates
      that the assay successfully measured S-OIV at a concentration of 1.8 * 10(2)
      PFU/mL in mimic solution, which contained PBS-diluted normal human nasal mucosa.
      Most importantly, the assay time took less than 20 min. From the results, the
      dual-channel PSPWB potentially offers great opportunity in developing an
      alternative PCR-free diagnostic method for rapid, sensitive, and accurate
      detection of viral pathogens with epidemiological relevance in clinical samples
      by using an appropriate pathogen-specific antibody.

PMID- 22401571
TI  - Seroprevalence of Toxoplasma gondii infection in dairy cattle in southern China.
AB  - BACKGROUND: As an obligate intracellular parasite, Toxoplasma gondii can infect
      humans and almost all warm-blooded animals. The consumption of raw or undercooked
      beef and milk is considered a risk for T. gondii infection in humans. However,
      little is known of T. gondii infection in dairy cattle in metropolitan Guangzhou,
      southern China. This study was performed to determine the seroprevalence of T.
      gondii in dairy cattle in Guangzhou, southern China. FINDINGS: Serum samples were
      collected from 350 dairy cattle on five farms in Guangzhou, China from 2009 to
      2010, and all of the 350 serum samples were examined for specific antibodies to
      T. gondii by indirect hemagglutination antibody test (IHA). The overall
      seroprevalence of T. gondii in dairy cattle was 5.7% (20/350). Among these
      examined dairy cattle, dairy cattle which were < 6 year old or >= 5 year old had
      the highest seroprevalence of 12.5% followed by those dairy cattle which were < 5
      year old or >= 4 year old (8%); dairy cattle with 3 pregnancies had the highest
      seroprevalence (11.5%), among the examined dairy cattle, although these
      differences were not statistically significant. CONCLUSIONS: The results of the
      present survey indicate that T. gondii infection is prevalent in dairy cattle of
      all age ranges in Guangzhou, southern China, which may be a risk factor for human
      infection with T. gondii in this region.Dong-Hui Zhou and Fu-Rong Zhao
      contributed equally.

PMID- 22401572
TI  - Microfluidic generation and selective degradation of biopolymer-based Janus
      microbeads.
AB  - We describe a microfluidic approach for generating Janus microbeads from
      biopolymer hydrogels. A flow-focusing device was used to emulsify the coflow of
      aqueous solutions of one or two different biopolymers in an organic phase to
      synthesize homo or hetero Janus microbeads. Biopolymer gelation was initiated, in
      the chip, by diffusion-controlled ionic cross-linking of the biopolymers. Pectin
      pectin (homo Janus) and, for the first time, pectin-alginate (hetero Janus)
      microbeads were produced. The efficiency of separation of the two hemispheres,
      which reflected mixing and convection phenomena, was investigated by confocal
      scanning laser microscopy (CSLM) of previously labeled biopolymers. The interface
      of the hetero Janus structure was clearly defined, whereas that of the homo Janus
      microbeads was poorly defined. The Janus structure was confirmed by subjecting
      each microbead hemisphere to specific enzymatic degradation. These new and
      original microbeads from renewable resources will open up opportunities for
      studying relationships between combined enzymatic hydrolysis and active compound
      release.

PMID- 22401573
TI  - Nonadaptive algorithms for threshold group testing with inhibitors and error
      tolerance.
AB  - A group test gives a positive (negative) outcome if it contains at least u (at
      most l) positive items, and an arbitrary outcome if the number of positive items
      is between thresholds l and u. This problem introduced by Damaschke is called
      threshold group testing. It is a generalization of classical group testing. Chen
      and Fu extended this problem to the error-tolerant version and first proposed
      efficient nonadaptive algorithms. In this article, we extend threshold group
      testing to the k-inhibitors model in which a test has a positive outcome if it
      contains at least u positives and at most k-1 inhibitors. By using (d + k - l, u;
      2e + 1]-disjunct matrix we provide nonadaptive algorithms for the threshold group
      testing model with k-inhibitors and at most e-erroneous outcomes. The decoding
      complexity is O(n(u+k) log n) for fixed parameters (d, u, l, k, e).

PMID- 22401574
TI  - Novel method for port implantation in lap-band surgery--transumbilical subfascial
      port implantation.
AB  - BACKGROUND: Some patients who have undergone a laparoscopic adjustable gastric
      band operation express dissatisfaction with visible scars or protrusion of the
      access port after sufficient weight loss. We hypothesized that subfascial port
      implantation could minimize those problems as well as port-related complications.
      SUBJECTS AND METHODS: We retrospectively reviewed the medical records of patients
      who underwent "transumbilical" subfascial port (SP) implantation between March
      2009 and July 2011. We compared these results with those of conventional
      placement of laparoscopic adjustable gastric band ports (CP) on the anterior
      rectus fascia by the four-point suture technique. The SP technique rendered the
      access port essentially nonpalpable, and therefore it could only be accessed
      under fluoroscopy. RESULTS: In total, 66 consecutive patients were enrolled into
      our study. Thirty-three patients underwent the SP procedure, and 33 patients
      underwent the CP procedure. Both groups were matched for age (31.4 +/- 6.5 years
      versus 34.0 +/- 8.7 years, P=.168), gender (female:male 30:3 versus 27:6,
      P=.282), and preoperative body mass index (36.6 +/- 5.4 kg/m(2) versus 36.9 +/-
      4.1 kg/m(2), P=.786). The mean follow-up period was 9.6 +/- 3.9 months for the SP
      group and 18.9 +/- 5.3 months for the CP group. During that period, the SP group
      tended to have a lower incidence of port infection (SP group, 0/33; CP group,
      3/33, P=.076), and no patients in the SP group complained of hypertrophic
      scarring at the port site (SP group, 0/33; CP group, 4/33; P=.04). Two patients
      in the CP group had port inversion/migration. Two patients in the CP group had
      port protrusion. Two patients in the CP group underwent port revision surgery
      (subfascial port) 6 months after port removal. One patient in the CP group
      underwent port exchange surgery under local anesthesia for port leakage. None of
      the patients in the SP group had any of the above port-related complications.
      CONCLUSIONS: Our preliminary results show that subfascial implantation of the
      laparoscopic adjustable gastric band port could minimize port-related
      complications during the weight loss phase.

PMID- 22401575
TI  - Strelitzia reginae leaf as a natural template for anisotropic wetting and
      superhydrophobicity.
AB  - Artificial surfaces that exhibit unidirectional water spreading and
      superhydrophobicity are obtained by  Strelitzia reginae  leaves. Both green and
      dried leaves are used, thus exploiting the plant senescence. We demonstrate that
      the natural drying process of the leaves strongly affects the surface morphology
      and wettability. Polymeric stamps from the green leaf show an arrangement of
      periodic microridges/microgrooves that favor anisotropic wetting, with a water
      contact angle (WCA) variation of about 21% along the two principal directions.
      Instead, the shrinkage of the leaf tissue, as a consequence of the natural
      dehydration process, induces an enhancement of the superficial corrugation. This
      results in the establishment of a superhydrophobic state, which shows a WCA of up
      to 160 degrees , and water rolling off.  S. reginae  leaves are therefore easily
      accessible stamps suitable for controlling wettability and realizing surfaces
      that exhibit various wetting behaviors.

PMID- 22401576
TI  - Tularaemia presenting as parapharyngeal abscess: case presentation.
AB  - OBJECTIVE: We report an extremely rare case of the oropharyngeal form of
      tularaemia, causing a parapharyngeal abscess. CASE REPORT: A 48-year-old woman
      presented with fever, sore throat, breathing difficulty and a right-sided neck
      swelling. This mass had previously been treated with penicillin without response,
      and had already been surgically drained once in another hospital. On physical
      examination, the tonsils were exudative and hypertrophic and the pharynx was
      hyperaemic. A fluctuant, 4 * 4 cm mass was seen on endoscopic examination,
      originating from the left parapharyngeal area and protruding towards the pyriform
      sinus, and partly obstructing the airway. Microagglutination test antibody titres
      for Francisella tularensis were positive (1/1280). The patient healed completely
      after definitive drainage of the abscess and antimicrobial therapy for 14 days
      (streptomycin, 2 * 1 g intramuscularly). CONCLUSION: Tularaemia should be
      considered in the differential diagnosis of patients presenting with
      tonsillopharyngitis, cervical lymphadenitis and parapharyngeal abscess who do not
      respond to treatment with penicillin, even if they do not live in an endemic
      region.

PMID- 22401577
TI  - Removing heavy metals in water: the interaction of cactus mucilage and arsenate
      (As (V)).
AB  - High concentrations of arsenic in groundwater continue to present health threats
      to millions of consumers worldwide. Particularly, affected communities in the
      developing world need accessible technologies for arsenic removal from drinking
      water. We explore the application of cactus mucilage, pectic polysaccharide
      extracts from Opuntia ficus-indica for arsenic removal. Synthetic arsenate (As
      (V)) solutions were treated with two extracts, a gelling extract (GE) and a
      nongelling extract (NE) in batch trials. The arsenic concentration at the air
      water interface was measured after equilibration. The GE and NE treated solutions
      showed on average 14% and 9% increases in arsenic concentration at the air-water
      interface respectively indicating that the mucilage bonded and transported the
      arsenic to the air-water interface. FTIR studies showed that the -CO groups
      (carboxyl and carbonyl groups) and -OH (hydroxyl) functional groups of the
      mucilage were involved in the interaction with the arsenate. Mucilage activity
      was greater in weakly basic (pH 9) and weakly acidic (pH 5.5) pH. This
      interaction can be optimized and harnessed for the removal of arsenic from
      drinking water. This work breaks the ground for the application of natural pectic
      materials to the removal of anionic metallic species from water.

PMID- 22401578
TI  - Core/shell NaGdF4:Nd(3+)/NaGdF4 nanocrystals with efficient near-infrared to near
      infrared downconversion photoluminescence for bioimaging applications.
AB  - We have synthesized core/shell NaGdF(4):Nd(3+)/NaGdF(4) nanocrystals with an
      average size of 15 nm and exceptionally high photoluminescence (PL) quantum
      yield. When excited at 740 nm, the nanocrystals manifest spectrally
      distinguished, near-infrared to near-infrared (NIR-to-NIR) downconversion PL
      peaked at ~900, ~1050, and ~1300 nm. The absolute quantum yield of NIR-to-NIR PL
      reached 40% for core-shell nanoparticles dispersed in hexane. Time-resolved PL
      measurements revealed that this high quantum yield was achieved through
      suppression of nonradiative recombination originating from surface states and
      cross relaxations between dopants. NaGdF(4):Nd(3+)/NaGdF(4) nanocrystals,
      synthesized in organic media, were further converted to be water-dispersible by
      eliminating the capping ligand of oleic acid. NIR-to-NIR PL bioimaging was
      demonstrated both in vitro and in vivo through visualization of the NIR-to-NIR PL
      at ~900 nm under incoherent lamp light excitation. The fact that both excitation
      and the PL of these nanocrystals are in the biological window of optical
      transparency, combined with their high quantum efficiency, spectral sharpness,
      and photostability, makes these nanocrystals extremely promising as optical
      biomaging probes.

PMID- 22401579
TI  - Non-negative matrix factorisation methods for the spectral decomposition of MRS
      data from human brain tumours.
AB  - BACKGROUND: In-vivo single voxel proton magnetic resonance spectroscopy (SV 1H
      MRS), coupled with supervised pattern recognition (PR) methods, has been widely
      used in clinical studies of discrimination of brain tumour types and follow-up of
      patients bearing abnormal brain masses. SV 1H-MRS provides useful biochemical
      information about the metabolic state of tumours and can be performed at short (<
      45 ms) or long (> 45 ms) echo time (TE), each with particular advantages. Short
      TE spectra are more adequate for detecting lipids, while the long-TE provides a
      much flatter signal baseline in between peaks but also negative signals for
      metabolites such as lactate. Both, lipids and lactate, are respectively
      indicative of specific metabolic processes taking place. Ideally, the information
      provided by both TE should be of use for clinical purposes. In this study, we
      characterise the performance of a range of Non-negative Matrix Factorisation
      (NMF) methods in two respects: first, to derive sources correlated with the mean
      spectra of known tissue types (tumours and normal tissue); second, taking the
      best performing NMF method for source separation, we compare its accuracy for
      class assignment when using the mixing matrix directly as a basis for
      classification, as against using the method for dimensionality reduction (DR).
      For this, we used SV 1H-MRS data with positive and negative peaks, from a widely
      tested SV 1H-MRS human brain tumour database. RESULTS: The results reported in
      this paper reveal the advantage of using a recently described variant of NMF,
      namely Convex-NMF, as an unsupervised method of source extraction from SV1H-MRS.
      Most of the sources extracted in our experiments closely correspond to the mean
      spectra of some of the analysed tumour types. This similarity allows accurate
      diagnostic predictions to be made both in fully unsupervised mode and using
      Convex-NMF as a DR step previous to standard supervised classification. The
      obtained results are comparable to, or more accurate than those obtained with
      supervised techniques. CONCLUSIONS: The unsupervised properties of Convex-NMF
      place this approach one step ahead of classical label-requiring supervised
      methods for the discrimination of brain tumour types, as it accounts for their
      increasingly recognised molecular subtype heterogeneity. The application of
      Convex-NMF in computer assisted decision support systems is expected to
      facilitate further improvements in the uptake of MRS-derived information by
      clinicians.

PMID- 22401580
TI  - gamma-Oryzanol reduces adhesion molecule expression in vascular endothelial cells
      via suppression of nuclear factor-kappaB activation.
AB  - gamma-Oryzanol (gamma-ORZ) is a mixture of phytosteryl ferulates purified from
      rice bran oil. In this study, we examined whether gamma-ORZ represents a
      suppressive effect on the lipopolysaccharide (LPS)-induced adhesion molecule
      expression on vascular endothelium. Treatment with LPS elevated the mRNA
      expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion
      molecule-1 (ICAM-1), and E-selectin in bovine aortic endothelial cells (BAECs).
      Pretreatment with gamma-ORZ dose-dependently decreased the LPS-mediated
      expression of these genes. Western blotting also revealed that pretreatment with
      gamma-ORZ dose-dependently inhibited LPS-induced VCAM-1 expression in human
      umbilical vein endothelial cells. Consistently, pretreatment with gamma-ORZ dose
      dependently reduced LPS-induced U937 monocyte adhesion to BAECs. In
      immunofluorescence, LPS caused nuclear factor-kappaB (NF-kappaB) nuclear
      translocation in 40% of BAECs, which indicates NF-kappaB activation. Pretreatment
      with gamma-ORZ, as well as its components (cycloartenyl ferulate, ferulic acid,
      or cycloartenol), dose-dependently inhibited LPS-mediated NF-kappaB activation.
      Collectively, our results suggested that gamma-ORZ reduced LPS-mediated adhesion
      molecule expression through NF-kappaB inhibition in vascular endothelium.

PMID- 22401581
TI  - IGFBP3 impedes aggressive growth of pediatric liver cancer and is epigenetically
      silenced in vascular invasive and metastatic tumors.
AB  - BACKGROUND: Hepatoblastoma (HB) is an embryonal liver neoplasm of early childhood
      with a poor prognosis for patients with distant metastases and vascular invasion.
      We and others have previously shown that the overexpression of insulin-like
      growth factor 2 (IGF2), loss of imprinting at the IGF2/H19 locus, and
      amplification of pleomorphic adenoma gene 1 (PLAG1) are common features in HB,
      suggesting a critical role of the IGF axis in hepatoblastomagenesis. In this
      study, we investigated the role of the insulin-like growth factor binding protein
      3 (IGFBP3), a known competitor of the IGF axis, in pediatric liver cancers.
      RESULTS: The IGFBP3 gene was highly expressed in normal pediatric livers but was
      heavily downregulated in four HB cell lines and the majority of HB primary tumors
      (26/36). Detailed methylation analysis of CpG sites in the IGFBP3 promoter region
      by bisulfite sequencing revealed a high degree of DNA methylation, which is
      causatively associated with the suppression of IGFBP3 in HB cell lines.
      Consequently, the treatment of HB cell lines with 5-aza-2'-deoxycytidine resulted
      in DNA demethylation and reactivation of the epigenetically silenced IGFBP3
      expression. Interestingly, IGFBP3 promoter methylation predominantly occurred in
      metastatic HB with vascular invasion. Restoring IGFBP3 expression in HB cells
      resulted in reduced colony formation, migration, and invasion. CONCLUSION: This
      study provides the first direct evidence that the reactivation of IGFBP3
      decreases aggressive properties of pediatric liver cancer cells and that IGFBP3
      promoter methylation might be used as an indicator for vessel-invasive tumor
      growth in HB patients.

PMID- 22401582
TI  - Reconstruction of protein side-chain conformational free energy surfaces from NMR
      derived methyl axis order parameters.
AB  - An analytical approach is developed for reconstructing site-specific methyl
      bearing protein side-chain conformational energy surfaces from NMR methyl axis
      order parameters (O(axis)(2)). Application of an enhanced sampling algorithm
      (adaptive biasing force) to molecular dynamics simulation of a protein, calcium
      bound calmodulin, reveals a nonlinear correlation between O(axis)(2) and the
      populations of rotamer states of protein side-chains, permitting the rotamer
      populations to be extracted directly from O(axis)(2). The analytical approach
      yields side-chain conformational distributions that are in excellent agreement
      with those obtained from the enhanced-sampling MD results.

PMID- 22401583
TI  - First case of Anaplasma platys infection in a dog from Croatia.
AB  - BACKGROUND: It is known that Anaplasma (A.) platys, the causative agent of
      infectious canine cyclic thrombocytopenia, is endemic in countries of the
      Mediterranean basin. However, few reports are available from the Balkans. This
      case report describes a dog, which was imported from Croatia to Germany in May
      2010. One month later the dog was presented to a local veterinarian in Germany
      due to intermittent/recurrent diarrhoea. Diagnostic tests were performed to
      identify infections caused by Anaplasma spp., Ehrlichia spp., Hepatozoon canis,
      Babesia spp., Leishmania spp., Borrelia burgdorferi and/or Dirofilaria immitis.
      FINDINGS: Haematological examination of a blood smear revealed basophilic
      inclusions in thrombocytes, which were confirmed as A. platys with a species
      specific real-time PCR. Additionally, an infection with Babesia (B.) vogeli was
      also detected (PCR and serology). No specific antibodies against Anaplasma
      antigen were detectable. Although the dog showed no specific clinical signs,
      thrombocytopenia, anaemia and elevated C-reactive protein (CRP) were observed.
      Sequencing of a 1,348-bp partial ribosomal RNA gene revealed highest homology to
      A. platys sequences from Thailand, Japan and France. CONCLUSIONS: A. platys was
      detected for first time in a dog imported from Croatia. As the dog was also co
      infected by B. vogeli, unique serological and haematological findings were
      recorded. Thrombocytopenia, anaemia and elevated values of C-reactive protein
      were the laboratory test abnormalities observed in this case. A. platys
      infections should be considered in dogs coming from Croatia and adjacent regions.

PMID- 22401584
TI  - Cyclohexyl analogues of ethylenediamine dipropanoic acid induce caspase
      independent mitochondrial apoptosis in human leukemic cells.
AB  - We investigated the cytotoxicity of recently synthesized (S,S)-ethylendiamine
      N,N'-di-2-(3-cyclohexyl)propanoic acid esters toward human leukemic cell lines
      and healthy blood mononuclear cells. Cell viability was assessed by acid
      phosphatase assay, apoptosis, and differentiation were analyzed by flow cytometry
      and electron microscopy, while intracellular localization of apoptosis-inducing
      factor (AIF) was determined by immunoblotting. It was demonstrated that methyl,
      ethyl, and n-propyl esters were toxic to HL-60, REH, MOLT-4, KG-1, JVM-2, and K
      562 leukemic cell lines, while the nonesterified parental compound and n-butyl
      ester were devoid of cytotoxic action. The ethyl ester exhibited the highest
      cytotoxic activity (IC50 10.7 MUM-45.4 MUM), which was comparable to that of the
      prototypical anticancer drug cisplatin. The observed cytotoxic effect in HL-60
      cells was associated with an increase in superoxide production and mitochondrial
      membrane depolarization, leading to apoptotic cell death characterized by
      phosphatidylserine externalization and DNA fragmentation in the absence of
      autophagic response. DNA fragmentation preceded caspase activation and followed
      AIF translocation from mitochondria to nucleus, which was indicative of caspase
      independent apoptotic cell death. HL-60 cells treated with subtoxic concentration
      of the compound displayed morphological signs of granulocytic differentiation
      (nuclear indentations and presence of cytoplasmic primary granules), as well as
      an increased expression of differentiation markers CD11b and CD15. The cyclohexyl
      analogues of ethylenediamine dipropanoic acid were also toxic to peripheral blood
      mononuclear cells of both healthy controls and leukemic patients, the latter
      being more sensitive. Our data demonstrate that the toxicity of the investigated
      cyclohexyl compounds against leukemic cell lines is mediated by caspase
      independent apoptosis associated with oxidative stress, mitochondrial
      dysfunction, and AIF translocation.

PMID- 22401585
TI  - Mechanism of RuO2 crystallization in borosilicate glass: an original in situ ESEM
      approach.
AB  - Ruthenium, a fission product arising from the reprocessing of spent uranium oxide
      (UOX) fuel, crystallizes in the form of acicular RuO(2) particles in high-level
      waste containment glass matrices. These particles are responsible for significant
      modifications in the physicochemical behavior of the glass in the liquid state,
      and their formation mechanisms are a subject of investigation. The chemical
      reactions responsible for the crystallization of RuO(2) particles with acicular
      or polyhedral shape in simplified radioactive waste containment glass are
      described. In situ high-temperature environmental scanning electron microscopy
      (ESEM) is used to follow changes in morphology and composition of the ruthenium
      compounds formed by reactions at high temperature between a simplified RuO(2)
      NaNO(3) precursor and a sodium borosilicate glass (SiO(2)-B(2)O(3)-Na(2)O). The
      key parameter in the formation of acicular or polyhedral RuO(2) crystals is the
      chemistry of the ruthenium compound under oxidized conditions (Ru(IV), Ru(V)).
      The precipitation of needle-shaped RuO(2) crystals in the melt might be
      associated with the formation of an intermediate Ru compound (Na(3)Ru(V)O(4))
      before dissolution in the melt, allowing Ru concentration gradients. The
      formation of polyhedral crystals is the result of the direct incorporation of
      RuO(2) crystals in the melt followed by an Ostwald ripening mechanism.

PMID- 22401586
TI  - Rab11-FIP3 is a cell cycle-regulated phosphoprotein.
AB  - BACKGROUND: Rab11 and its effector molecule, Rab11-FIP3 (FIP3), associate with
      recycling endosomes and traffic into the furrow and midbody of cells during
      cytokinesis. FIP3 also controls recycling endosome distribution during
      interphase. Here, we examine whether phosphorylation of FIP3 is involved in these
      activities. RESULTS: We identify four sites of phosphorylation of FIP3 in vivo, S
      102, S-280, S-347 and S-450 and identify S-102 as a target for Cdk1-cyclin B in
      vitro. Of these, we show that S-102 is phosphorylated in metaphase and is
      dephosphorylated as cells enter telophase. Over-expression of FIP3-S102D
      increased the frequency of binucleate cells consistent with a role for this
      phospho-acceptor site in cytokinesis. Mutation of S-280, S-347 or S-450 or other
      previously identified phospho-acceptor sites (S-488, S-538, S-647 and S-648) was
      without effect on binucleate cell formation and did not modulate the distribution
      of FIP3 during the cell cycle. In an attempt to identify a functional role for
      FIP3 phosphorylation, we report that the change in FIP3 distribution from
      cytosolic to membrane-associated observed during progression from anaphase to
      telophase is accompanied by a concomitant dephosphorylation of FIP3. However, the
      phospho-acceptor sites identified here did not control this change in
      distribution. CONCLUSIONS: Our data thus identify FIP3 as a cell cycle regulated
      phosphoprotein and suggest dephosphorylation of FIP3 accompanies its
      translocation from the cytosol to membranes during telophase. S102 is
      dephosphorylated during telophase; mutation of S102 exerts a modest effect on
      cytokinesis. Finally, we show that de/phosphorylation of the phospho-acceptor
      sites identified here (S-102, S-280, S-347 and S-450) is not required for the
      spatial control of recycling endosome distribution or function.

PMID- 22401587
TI  - Laparoscopic Nissen-Rossetti fundoplication for gastroesophageal reflux disease
      patients after 2-year follow-up.
AB  - INTRODUCTION: Gastroesphageal reflux disease (GERD) is a common condition in the
      general population, affecting patients' quality of life and predisposing to
      Barrett's esophagus and its most fearsome complication, esophageal
      adenocarcinoma. The aim of this study is to compare objective and subjective
      outcomes of laparoscopic Nissen-Rossetti fundoplication after 2 years of follow
      up. SUBJECTS AND METHODS: Seventy-six GERD patients underwent laparoscopic Nissen
      Rossetti fundoplication. Patients were subjected to close follow-up. RESULTS: The
      DeMeester and Johnson score average decreased from a mean preoperative value of
      35.48 (SD+/-40.24) to 9.83 (SD+/-6.40) at 6 months; at 12 months it was 11.44
      (SD+/-10.28), and at 24 months it was 10.25 (SD+/-5.61). GERD Health-Related
      Quality of Life decreased from a preoperative value of 23.04 (SD+/-11.59) to 9.84
      (SD+/-8.98) at 6 months, 8.34 (SD+/-8.98) at 12 months, and 6.8 (SD+/-6.46) at 24
      months. The Short Form-36 measurement showed significant improvement.
      CONCLUSIONS: GERD patients need adequate reflux control. Successful antireflux
      surgery is more effective than medical therapy in preventing both acid and bile
      reflux. Surgical therapy is effective in terms of reflux control and improvement
      in quality of life. Strict and rigorous follow-up with both subjective and
      objective tests is important in order to identify asymptomatic recurrence of
      reflux after surgery.

PMID- 22401588
TI  - A study on the learning curve of the robotic virtual reality simulator.
AB  - PURPOSE: A robotic virtual reality simulator (dV-TrainerTM, Mimic Technologies)
      has been accepted as an effective training tool for the da Vinci((r)) Surgical
      System (Intuitive Surgical, Inc.) in previous reports. However, there are no data
      available so far on how much time is required for an individual using the
      simulator to become proficient. We investigated how long and how many
      performances it takes to gain proficiency with the robotic virtual reality
      simulator through the learning curve. SUBJECTS AND METHODS: The novice group
      included 20 medical students who had no previous experience. The "Tube 2" task, a
      program released for the dV-Trainer that imitates a vesicourethral anastomosis,
      was repeated more than 80 times to obtain the plateau of the learning curve. The
      learning curve of "Tube 2" was obtained through the S-curve trend model and
      cumulative sum control chart graph. RESULTS: In the comparison of the initial and
      final sessions, every parameter such as mean time, collision, and critical errors
      was significantly improved. The repeat count for acquiring sufficient proficiency
      was 74 times, and the total amount of time invested for this was calculated as
      about 4 hours. The mean time at the plateau of the learning curve was 138
      seconds. CONCLUSIONS: Our study showed that the robotic virtual reality simulator
      (dV-Trainer) can yield sufficient improvement in technical performance in the
      "Tube 2" task within 4 hours. The simulator improves the technical surgical
      performance, but the development of more applications to reflect actual surgical
      situations is needed to improve and maximize the usefulness of the simulator.

PMID- 22401589
TI  - Classifier assessment and feature selection for recognizing short coding
      sequences of human genes.
AB  - With the ever-increasing pace of genome sequencing, there is a great need for
      fast and accurate computational tools to automatically identify genes in these
      genomes. Although great progress has been made in the development of gene-finding
      algorithms during the past decades, there is still room for further improvement.
      In particular, the issue of recognizing short exons in eukaryotes is still not
      solved satisfactorily. This article is devoted to assessing various linear and
      kernel-based classification algorithms and selecting the best combination of Z
      curve features for further improvement of the issue. Eight state-of-the-art
      linear and kernel-based supervised pattern recognition techniques were used to
      identify the short (21-192 bp) coding sequences of human genes. By measuring the
      prediction accuracy, the tradeoff between sensitivity and specificity and the
      time consumption, partial least squares (PLS) and kernel partial least squares
      (KPLS) algorithms were verified to be the most optimal linear and kernel-based
      classifiers, respectively. A surprising result was that, by making good use of
      the interpretability of the PLS and the Z-curve methods, 93 Z-curve features were
      proved to be the best selective combination. Using them, the average recognition
      accuracy was improved as high as 7.7% by means of KPLS when compared with what
      was obtained by the Fisher discriminant analysis using 189 Z-curve variables (Gao
      and Zhang, 2004 ). The used codes are freely available from the following
      approaches (implemented in MATLAB and supported on Linux and MS Windows): (1)
      SVM: http://www.support-vector-machines.org/SVM_soft.html. (2) GP:
      http://www.gaussianprocess.org. (3) KPLS and KFDA: Taylor, J.S., and Cristianini,
      N. 2004. Kernel Methods for Pattern Analysis. Cambridge University Press,
      Cambridge, UK. (4) PLS: Wise, B.M., and Gallagher, N.B. 2011. PLS-Toolbox for use
      with MATLAB: ver 1.5.2. Eigenvector Technologies, Manson, WA. Supplementary
      Material for this article is available at www.liebertonline.com/cmb.

PMID- 22401590
TI  - Algorithms for the design of maximum hydropathic complementarity molecules.
AB  - In this article, we address the problem of designing a string with optimal
      complementarity properties with respect to another given string according to a
      given criterion. The motivation comes from a drug design application, in which
      the complementarity between two sequences (proteins) is measured according to the
      values of the hydropathic coefficients associated with the sequence elements
      (amino acids). We present heuristic and exact optimization algorithms, and we
      report on some computational experiments on amino peptides taken from Semaphorin
      and human Interleukin-1beta, which have already been investigated in the
      literature using heuristic algorithms. With our techniques, we proved the
      optimality of a known solution for Semaphorin-3A, and we discovered several other
      optimal and near-optimal solutions in a short computing time; we also found in
      fractions of a second an optimal solution for human interleukin-1beta, whose
      complementary value is one order of magnitude better than previously known ones.
      The source code of a prototype C++ implementation of our algorithms is freely
      available for noncommercial use on the web. As a main result, we showed that in
      this context mathematical programming methods are more successful than
      heuristics, such as simulated annealing. Our algorithm unfolds its potential,
      especially when different measures could be used for scoring peptides, and is
      able to provide not only a single optimal solution, but a ranking of provable
      good ones; this ranking can then be used by biologists as a starting basis for
      further refinements, simulations, or in vitro experiments.

PMID- 22401591
TI  - Coalescent-based DNA barcoding: multilocus analysis and robustness.
AB  - DNA barcoding is the assignment of individuals to species using standardized
      mitochondrial sequences. Nuclear data are sometimes added to the mitochondrial
      data to increase power. A barcoding method for analysing mitochondrial and
      nuclear data is developed. It is a Bayesian method based on the coalescent model.
      Then this method is assessed using simulated and real data. It is found that
      adding nuclear data can reduce the number of ambiguous assignments. Finally, the
      robustness of coalescent-based barcoding to departures from model assumptions is
      studied using simulations. This method is found to be robust to past population
      size variations, to within-species population structures, and to designs that
      poorly sample populations within species. Supplementary Material is available
      online at www.liebertonline.com/cmb.

PMID- 22401592
TI  - Probabilistic logic methods and some applications to biology and medicine.
AB  - For the computational analysis of biological problems-analyzing data, inferring
      networks and complex models, and estimating model parameters-it is common to use
      a range of methods based on probabilistic logic constructions, sometimes
      collectively called machine learning methods. Probabilistic modeling methods such
      as Bayesian Networks (BN) fall into this class, as do Hierarchical Bayesian
      Networks (HBN), Probabilistic Boolean Networks (PBN), Hidden Markov Models (HMM),
      and Markov Logic Networks (MLN). In this review, we describe the most general of
      these (MLN), and show how the above-mentioned methods are related to MLN and one
      another by the imposition of constraints and restrictions. This approach allows
      us to illustrate a broad landscape of constructions and methods, and describe
      some of the attendant strengths, weaknesses, and constraints of many of these
      methods. We then provide some examples of their applications to problems in
      biology and medicine, with an emphasis on genetics. The key concepts needed to
      picture this landscape of methods are the ideas of probabilistic graphical
      models, the structures of the graphs, and the scope of the logical language
      repertoire used (from First-Order Logic [FOL] to Boolean logic.) These concepts
      are interlinked and together define the nature of each of the probabilistic logic
      methods. Finally, we discuss the initial applications of MLN to genetics, show
      the relationship to less general methods like BN, and then mention several
      examples where such methods could be effective in new applications to specific
      biological and medical problems.

PMID- 22401593
TI  - Apolipoprotein-defined lipoprotein abnormalities in rheumatoid arthritis patients
      and their potential impact on cardiovascular disease.
AB  - OBJECTIVES: The aim of this study was to explore apolipoprotein-defined
      lipoproteins for abnormalities when comparing non-rheumatological controls to
      rheumatoid arthritis (RA) patients. METHODS: Apolipoprotein and lipoprotein
      profiles were measured on 94 RA patients and 79 controls by immunoturbidimetric
      procedures, electroimmunoassays, and immunoprecipitation. Differences between
      means were tested with a two-sided Student t test with Satterthwaite adjustment.
      p-values were adjusted for multiple comparisons using the Bonferroni procedure.
      RESULTS: RA patients had significantly higher levels of total cholesterol (TC),
      triglycerides (TG), and very low density lipoprotein cholesterol (VLDL-C) than
      controls, but no significant differences in the levels of high density
      lipoprotein cholesterol (HDL-C) and LDL-C. RA patients had significantly lower
      levels of apolipoprotein (apo)A-I and lipoprotein (Lp)A-I:A-II, but no difference
      in levels of LpA-I than normal controls. There was a significant difference in
      the levels of LpB:C but not in LpB:C:E between RA patients and controls. The main
      abnormality among apoB lipoproteins was the significantly increased concentration
      of the LpA-II:B:C:D:E subclass in RA patients in comparison with controls. The
      high levels of LpA-II:B:C:D:E are also reflected in significantly increased
      levels of apoC-III, and apoC-III bound to apoB lipoproteins. CONCLUSION: The LpA
      II:B:C:D:E subclass has potential as a new marker for cardiovascular disease
      (CVD) in RA patients.

PMID- 22401594
TI  - Diagnostic difficulties of plunging ranula: case series.
AB  - OBJECTIVES: To evaluate common pitfalls in diagnosing complicated plunging
      ranula, either due to misidentification of plunging ranula or alternative
      pathology (i.e. false negatives or false positives, respectively). METHODS: A
      review of cases of plunging ranula seen in Middlemore Hospital, New Zealand, was
      performed. Diagnostically uncertain cases were identified and reviewed, taking
      particular note of clinical, radiological and surgical findings. RESULTS: From
      our database, 12 cases were found to have had a complicated diagnosis of plunging
      ranula. Ten cases were false negatives: four were treated as abscesses, four as
      simple cysts, one as a thyroglossal cyst and one as a cystic hygroma. Two cases
      were false positives: one was found to be a thyroglossal cyst and the other a
      lipoma. CONCLUSION: The diagnosis of plunging ranula is usually straightforward,
      with simple surgical management. Misdiagnosis can lead to recurrence of symptoms
      and inappropriate management, with the associated risks, complications and
      frustrations of surgery.

PMID- 22401595
TI  - Lab-on-fiber technology: toward multifunctional optical nanoprobes.
AB  - We propose a reliable fabrication process enabling the integration of dielectric
      and metallic nanostructures on the tip of optical fibers, thus representing a
      further step in the "lab-on-fiber" technology roadmap. The proposed fabrication
      procedure involves conventional deposition and nanopatterning techniques,
      typically used for planar devices, but here adapted to directly operate on
      optical fiber tip. Following this approach, we demonstrate a first technological
      platform based on the integration onto the optical fiber tip of two-dimensional
      hybrid metallo-dielectric nanostructures supporting localized surface plasmon
      resonances. By means of experimental measurements and full-wave numerical
      simulations, we characterize these resonant phenomena and investigate the
      underlying physics. We show that resonances can be easily tuned by acting on the
      physical and geometrical parameters of the structure. Moreover, with a view
      toward possible applications, we present some preliminary results demonstrating
      how the proposed device can work effectively as an optical probe for label-free
      chemical and biological sensing as well as a microphone for acoustic wave
      detection.

PMID- 22401597
TI  - 9,10-seco-9,19-cyclolanostane triterpene from Salix caprea L. (goat willow).
AB  - Chemical investigation of low polar solvent extract of Salix caprea through
      chromatographic techniques led to the isolation of new triterpene as
      1alpha,3beta,25-trihydroxy-9(11)-ene-16-one-9,10-seco-9,19-cyclolanostane (1)
      along with fatty alcohols. The structure of compound 1 was established by IR,
      HRESI/MS and NMR including 1D and 2D experiments. The compound 1 showed moderate
      in vitro antiplasmodial activity.

PMID- 22401596
TI  - STAT6 expression in T cells, alveolar macrophages and bronchial biopsies of
      normal and asthmatic subjects.
AB  - BACKGROUND: Asthma is characterised by increased numbers of Th2-like cells in the
      airways and IgE secretion. Generation of Th2 cells requires interleukin (IL)-4
      and IL-13 acting through their specific receptors and activating the
      transcription factor, signal transducer and activator of transcription 6 (STAT6).
      STAT6 knockout mice fail to produce IgE, airway hyperresponsiveness and
      bronchoalveolar lavage eosinophilia after allergen sensitisation, suggesting a
      critical role for STAT6 in allergic responses. METHODS: We have investigated the
      expression of STAT6 in peripheral blood T-lymphocytes, alveolar macrophages and
      bronchial biopsies from 17 normal subjects and 18 mild-moderate steroid-naive
      stable asthmatic patients. RESULTS: STAT6 expression was variable and was
      detected in T-lymphocytes, macrophages and bronchial epithelial cells from all
      subjects with no difference between normal and stable asthmatic subjects.
      CONCLUSIONS: STAT6 expression in different cells suggests that it may be
      important in regulating the expression of not only Th2-like cytokines in T cells
      of man, but may also regulate STAT-inducible genes in alveolar macrophages and
      airway epithelial cells.

PMID- 22401598
TI  - Altered expression of the TCR signaling related genes CD3 and FcepsilonRIgamma in
      patients with aplastic anemia.
AB  - BACKGROUND: Aplastic anemia (AA) is characterized by pancytopenia and bone marrow
      hypoplasia, which results from immune-mediated hematopoiesis suppression.
      Understanding the pathophysiology of the immune system, particularly T cells
      immunity, has led to improved AA treatment over the past decades. However,
      primary and secondary failure after immunosuppressive therapy is frequent. Thus,
      knowledge of the immune mechanisms leading to AA is crucial to fundamentally
      understand the disease. FINDINGS: To elucidate the T cell receptor (TCR) signal
      transduction features in AA, the expression levels of CD3gamma, delta, epsilon
      and zeta chain and FcepsilonRIgamma genes, which are involved in TCR signal
      transduction, and the negative correlation of the expression levels between the
      CD3zeta and FcepsilonRIgamma genes in T cells from peripheral blood mononuclear
      cells (PBMCs) were analyzed. Real-time RT-PCR using the SYBR Green method was
      used to detect the expression level of these genes in PBMCs from 18 patients with
      AA and 14 healthy individuals. The beta2microglobulin gene (beta2M) was used as
      an endogenous reference. The expression levels of the CD3gamma, CD3delta,
      CD3epsilon and CD3zeta genes in patients with AA were significantly increased
      compared to a healthy control group, whereas the FcepsilonRIgamma gene expression
      level was significantly decreased in patients with AA in comparison with the
      healthy control group. Moreover, the negative correlation of the expression
      levels between the CD3zeta and FcepsilonRIgamma genes was lost. CONCLUSIONS: To
      our knowledge, this is the first report of the CD3gamma, CD3delta, CD3epsilon,
      CD3zeta and FcepsilonRIgamma gene expression in patients with AA. The abnormally
      expressed TCR signaling related genes may relate to T cells dysfunction in AA.

PMID- 22401599
TI  - Two cases of atypical Whipple's disease associated with cytoplasmic ANCA of
      undefined specificity.

PMID- 22401600
TI  - Satiety-enhancing products for appetite control: science and regulation of
      functional foods for weight management.
AB  - The current review considers satiety-based approaches to weight management in the
      context of health claims. Health benefits, defined as beneficial physiological
      effects, are what the European Food Safety Authority bases their recommendations
      on for claim approval. The literature demonstrates that foods that target within
      meal satiation and post-meal satiety provide a plausible approach to weight
      management. However, few ingredient types tested produce the sustainable and
      enduring effects on appetite accompanied by the necessary reductions in energy
      intake required to claim satiety/reduction in hunger as a health benefit.
      Proteins, fibre types, novel oils and carbohydrates resistant to digestion all
      have the potential to produce beneficial short-term changes in appetite (proof-of
      concept). The challenge remains to demonstrate their enduring effects on appetite
      and energy intake, as well as the health and consumer benefits such effects
      provide in terms of optimising successful weight management. Currently, the
      benefits of satiety-enhancing ingredients to both consumers and their health are
      under researched. It is possible that such ingredients help consumers gain
      control over their eating behaviour and may also help reduce the negative
      psychological impact of dieting and the physiological consequences of energy
      restriction that ultimately undermine weight management. In conclusion, industry
      needs to demonstrate that a satiety-based approach to weight management, based on
      single-manipulated food items, is sufficient to help consumers resist the
      situational and personal factors that drive overconsumption. Nonetheless, we
      possess the methodological tools, which when employed in appropriate designs, are
      sufficient to support health claims.

PMID- 22401601
TI  - Therapeutic applications for subcutaneous triptans in the acute treatment of
      migraine.
AB  - BACKGROUND: The features of migraine attacks and the contexts in which migraine
      attacks occur vary from attack to attack and from patient to patient. Current
      treatment strategies, which are dominated by the use of oral forms of migraine
      medication, do not address this patient-to-patient and attack-to-attack
      heterogeneity. While current therapies, and, in particular, oral triptan tablets
      can be effective for many types of migraine attacks that a patient can
      experience, they may not be the optimum treatment for every migraine in every
      patient. SCOPE: This clinical review of subcutaneous sumatriptan discusses its
      characteristics, efficacy, and tolerability and considers its place in clinical
      practice. The review focuses particularly on several specific clinical settings
      in which subcutaneous sumatriptan might be a more appropriate therapeutic choice
      than the oral triptan tablet. FINDINGS: Of the triptan formulations, subcutaneous
      sumatriptan is the most rapidly absorbed and demonstrates a favorable
      pharmacokinetic profile. Data from randomized, double-blind, clinical trials and
      studies of patients' perceptions and preferences suggest that subcutaneous
      sumatriptan can be particularly useful to help restore normal work functioning,
      for migraine attacks that cannot be treated early in their course, for migraine
      attacks associated with gastrointestinal symptoms, such as nausea or vomiting,
      and for difficult-to-treat migraines, including early-morning migraine and
      menstrual migraine. The majority of patients (9 in 10) trying subcutaneous
      sumatriptan indicated that they will use it again. Patients not fully satisfied
      with previous triptan therapy reported enhanced satisfaction with, and confidence
      in, treatment after trying subcutaneous sumatriptan. CONCLUSIONS: By virtue of
      their availability as multiple compounds and in multiple formulations including
      oral, intranasal, and injectable forms, triptans can be used to customize
      migraine therapy to the individual patient and the individual migraine attack.
      Due to its route of delivery and favorable pharmacokinetic profile, subcutaneous
      triptans may represent an attractive alternative for specific clinical settings.
      Subcutaneous sumatriptan can play a key role in maximizing likelihood of pain
      free response and rapid return to normal daily activities and, as such, should be
      considered an important part of the treatment armamentarium for migraine.

PMID- 22401602
TI  - Challenges with current inhaled treatments for chronic Pseudomonas aeruginosa
      infection in patients with cystic fibrosis.
AB  - BACKGROUND: Pseudomonas aeruginosa (Pa) is the predominant pathogen infecting the
      airways of patients with cystic fibrosis (CF). Initial colonization is usually
      transient and associated with non-mucoid strains, which can be eradicated if
      identified early. This strategy can prevent, or at least delay, chronic Pa
      infection, which eventually develops in the majority of patients by their late
      teens or early adulthood. This article discusses the management and latest
      treatment developments of Pa lung infection in patients with CF, with a focus on
      nebulized antibiotic therapy. METHODS: PubMed was searched to identify English
      language articles published up until August 2011 using combinations of the
      following key words: 'antibiotics', 'chronic', 'cystic fibrosis', 'eradication',
      'exacerbations', 'guidelines', 'inhaled', 'intravenous', 'lung infection',
      'burden', 'adherence', 'patient segregation', 'pseudomonas aeruginosa' and
      'resistance'. FINDINGS: Antibiotics form a central part of the treatment regimens
      for chronic Pa lung infection. Current treatment guidelines recommend that
      patients with chronic pulmonary infection with Pa should receive long-term
      inhaled anti-pseudomonal therapy to preserve lung function, and to reduce the
      frequency of pulmonary exacerbations and hospital admissions. While antibiotic
      resistance seems to increase with frequent antibiotic use, this does not appear
      to impact on clinical outcome. Negative aspects of therapy include the time
      needed for drug administration and subsequent cleaning of the equipment. These
      factors cause a significant treatment burden and impact on adherence. The
      availability of more convenient formulations and delivery vehicles for anti
      pseudomonal antibiotics may help overcome some of these challenges. CONCLUSIONS:
      Current challenges in the management of CF patients with chronic Pa lung
      infection are numerous. The availability of novel anti-pseudomonal antibiotic
      formulations/devices is anticipated to improve treatment adherence in patients
      with CF, and could improve clinical outcomes. Thus, there is hope for improved
      survival in individuals with CF suffering from chronic pulmonary infection with
      Pa.

PMID- 22401603
TI  - Formation and plasmonic response of self-assembled layers of colloidal gold
      nanorods and branched gold nanoparticles.
AB  - The plasmonic properties of self-assembled layers of rod- and branched-shaped
      gold nanoparticles were investigated using optical techniques. Nanoparticles were
      synthesized by a surfactant-guided, seed-mediated growth method. The layers were
      obtained by gradual assembly of nanoparticles at the interface between a polar
      and a nonpolar solvent and were transferred to a glass slide. Polarization and
      angle-dependent extinction measurements showed that the layers made of gold
      nanorods were governed by an effective medium response. The response of the
      layers made by branched gold particles was characterized by random light
      scattering. Microscopic mapping of the spatial mode structure demonstrates a
      uniform optical response of the nanoparticle layers down to a submicrometer
      length scale.

PMID- 22401604
TI  - Symmetrical P4 cleavage at cobalt: characterization of intermediates on the way
      from P4 to coordinated P2 units.
AB  - Degradation of white phosphorus (P(4)) in the coordination sphere of transition
      metals is commonly divided into two major pathways depending on the P(x) ligands
      obtained. Consecutive metal-assisted P-P bond cleavage of four bonds of the P(4)
      tetrahedron leads to complexes featuring two P(2) ligands (symmetric cleavage) or
      one P(3) and one P(1) ligand (asymmetric cleavage). A systematic investigation of
      the degradation of white phosphorus P(4) to coordinated MU,eta(2:2)-bridging
      diphosphorus ligands in the coordination sphere of cobalt is presented herein as
      well as isolation of each of the decisive intermediates on the reaction pathway.
      The olefin complex [Cp*Co((i)Pr(2)Im)(eta(2)-C(2)H(4))], 1 (Cp* = eta(5)
      C(5)Me(5), (i)Pr(2)Im = 1,3-di-isopropylimidazolin-2-ylidene), reacts with P(4)
      to give [Cp*Co((i)Pr(2)Im)(eta(2)-P(4))], 2, the insertion product of
      [Cp*Co((i)Pr(2)Im)] into one of the P-P bonds. Addition of a further equivalent
      of the Co(I) complex [Cp*Co((i)Pr(2)Im)(eta(2)-C(2)H(4))], 1, induces cleavage of
      a second P-P bond to yield the dinuclear complex
      [{Cp*Co((i)Pr(2)Im)}(2)(MU,eta(2:2)-P(4))], 3, in which a kinked cyclo-P(4)(4-)
      ligand bridges two cobalt atoms. Consecutive dissociation of the N-heterocyclic
      carbene with concomitant rearrangement of the cyclo-P(4) ligand and P-P
      dissociation leads to complexes [Cp*Co(MU,eta(4:2)-P(4))Co((i)Pr(2)Im)Cp*], 4,
      featuring a P(4) chain, and [{Cp*Co(MU,eta(2:2)-P(2))}(2)], 5, in which two
      isolated P(2)(2-) ligands bridge two [Cp*Co] fragments. Each of these reactions
      is quantitative if performed on an NMR scale, and each compound can be isolated
      in high yields and large quantities.

PMID- 22401605
TI  - Preparation of accurate, low-concentration gas cylinder standards by cryogenic
      trapping of a permeation tube gas stream.
AB  - National and international measurements are underpinned by accurate, low
      concentration standards. These standards are typically produced gravimetrically,
      or volumetrically, by a series of dilutions of the pure material by the balance
      gas. This blend technique is time-consuming and may involve the handling of pure,
      hazardous material. These problems have been overcome by developing a novel blend
      technique whereby the process gas stream, from an appropriate permeation tube,
      was cryogenically trapped in an aluminum cylinder. The permeation rate of the
      component is monitored by real time mass determinations using a magnetic
      suspension balance system. With the combination of the real-time calculated
      permeation rate, plus the use of a dilution system, a one step production of a
      very low concentration of the minor component in nitrogen gas can be achieved.
      This method was used to prepare low MUmol/mol standards of propane, a known
      stable compound. Analysis of a conventional gravimetrically prepared 10 MUmol/mol
      propane standard and a cryogenically prepared standard via a permeation gas
      stream resulted in agreement between the two of <0.1% at 10 MUmol/mol, confirming
      the accuracy of the permeation method. After confirmation of the validity of the
      permeation/cryogenic trapping system, the propane permeation tube was replaced
      with a methyl mercaptan tube (a toxic, reactive compound) in balance nitrogen.
      After cryogenically trapping the methyl mercaptan output stream from the
      permeation system into a cylinder, the output stream and the cylinder gas mixture
      were analyzed. The results showed agreement of <0.6% for methyl mercaptan at 5,
      10, 15, and 20 MUmol/mol to the expected blend concentration, thereby
      demonstrating the validity of the method.

PMID- 22401606
TI  - Morphostasis in a novel eukaryote illuminates the evolutionary transition from
      phagotrophy to phototrophy: description of Rapaza viridis n. gen. et sp.
      (Euglenozoa, Euglenida).
AB  - BACKGROUND: Morphostasis of traits in different species is necessary for
      reconstructing the evolutionary history of complex characters. Studies that place
      these species into a molecular phylogenetic context test hypotheses about the
      transitional stages that link divergent character states. For instance, the
      transition from a phagotrophic mode of nutrition to a phototrophic lifestyle has
      occurred several times independently across the tree of eukaryotes; one of these
      events took place within the Euglenida, a large group of flagellates with diverse
      modes of nutrition. Phototrophic euglenids form a clade that is nested within
      lineages of phagotrophic euglenids and that originated through a secondary
      endosymbiosis with green algae. Although it is clear that phototrophic euglenids
      evolved from phagotrophic ancestors, the morphological disparity between species
      representing these different nutritional modes remains substantial. RESULTS: We
      cultivated a novel marine euglenid, Rapaza viridis n. gen. et sp. ("green
      grasper"), and a green alga, Tetraselmis sp., from the same environment. Cells of
      R. viridis were comprehensively characterized with light microscopy, SEM, TEM,
      and molecular phylogenetic analysis of small subunit rDNA sequences.
      Ultrastructural and behavioral observations demonstrated that this isolate
      habitually consumes a specific strain of Tetraselmis prey cells and possesses a
      functional chloroplast that is homologous with other phototrophic euglenids. A
      novel feeding apparatus consisting of a reduced rod of microtubules facilitated
      this first and only example of mixotrophy among euglenids. R. viridis also
      possessed a robust photoreception apparatus, two flagella of unequal length,
      euglenoid movement, and a pellicle consisting of 16 strips and one (square
      shaped) whorl of posterior strip reduction. The molecular phylogenetic data
      demonstrated that R. viridis branches as the nearest sister lineage to
      phototrophic euglenids. CONCLUSIONS: The unusual combination of features in R.
      viridis combined with its molecular phylogenetic position completely conforms to
      the expected transitional stage that occurred during the early evolution of
      phototrophic euglenids from phagotrophic ancestors. The marine mixotrophic mode
      of nutrition, the preference for green algal prey cells, the structure of the
      feeding apparatus, and the organization of the pellicle are outstanding examples
      of morphostasis that clarify pivotal stages in the evolutionary history of this
      diverse group of microbial eukaryotes.

PMID- 22401607
TI  - Experiences of patients with chronic gastrointestinal conditions: in their own
      words.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD)
      are chronic conditions affecting millions of individuals in the United States.
      The symptoms are well-documented and can be debilitating. How these chronic
      gastrointestinal (GI) conditions impact the daily lives of those afflicted is not
      well documented, especially from a patient's perspective. METHODS: Here we
      describe data from a series of 22 focus groups held at three different academic
      medical centers with individuals suffering from chronic GI conditions. All focus
      groups were audio recorded and transcribed. Two research team members
      independently analyzed transcripts from each focus group following an agreed upon
      coding scheme. RESULTS: One-hundred-thirty-six individuals participated in our
      study, all with a chronic GI related condition. They candidly discussed three
      broad themes that characterize their daily lives: identification of disease and
      personal identity, medications and therapeutics, and daily adaptations. These all
      tie to our participants trying to deal with symptoms on a daily basis. We find
      that a recurrent topic underlying these themes is the dichotomy of experiencing
      uncertainty and striving for control. CONCLUSIONS: Study participants' open
      dialogue and exchange of experiences living with a chronic GI condition provide
      insight into how these conditions shape day-to-day activities. Our findings
      provide fertile ground for discussions about how clinicians might best
      facilitate, acknowledge, and elicit patients' stories in routine care to better
      address their experience of illness.

PMID- 22401608
TI  - An NMR-based metabonomic investigation of the subacute effects of melamine in
      rats.
AB  - The subacute toxic effects of 28 days of exposure to three dosages (250, 500,
      1000 mg/kg/day) of melamine on Wistar rats were investigated using nuclear
      magnetic resonance spectra, histopathological examination, and biochemical
      analysis. Rats treated with melamine developed adverse health effects compared to
      the controls, including decrease in body weight and kidney damage. Blood
      biochemical analysis showed that the blood urea nitrogen and creatinine increased
      distinctly compared to the control group. Urinary metabonomic analysis indicated
      that melamine caused an increase in succinate and citrate. Serum metabonomic
      analysis showed that the lowest dose led to an increase in dimethylglycine, N
      acetylglycoprotein (NAC), accompanied by a decrease in taurine and glucose. Rats
      treated with the highest dose developed high levels of serum choline and 3
      hydroxybutyrate (3-HB) together with low lactate levels. Metabonomic analysis of
      liver tissue indicated that melamine caused an increase in NAC, choline, and
      creatine, accompanied by a decrease in lactate, trimethylamine-N-oxide,
      glutamate, and glucose. All three dosages resulted in an increase in glutamate,
      lactate, choline, glucose, and animo acids and a decrease in 3-HB and pyruvate in
      aqueous kidney extract. These results indicate that melamine not only caused
      renal disfunction but also disturbed the liver's glucose, protein, and nitrogen
      metabolism.

PMID- 22401609
TI  - Is your workplace a PPE?

PMID- 22401610
TI  - Images and emergency nursing.

PMID- 22401611
TI  - Solutions for ED overcrowding: increasing urgent care centers.

PMID- 22401612
TI  - ED crowding and throughput more than just an ED problem.

PMID- 22401613
TI  - Priority preparedness issues.

PMID- 22401614
TI  - International membership.

PMID- 22401615
TI  - Response to January JEN editor's message.

PMID- 22401616
TI  - The use of and satisfaction with the Emergency Severity Index.
AB  - INTRODUCTION: The Emergency Severity Index (ESI) is a 5-level emergency
      department triage algorithm designed to facilitate the sorting and streaming of
      patients. The purpose of this study was to assess the use of the ESI in emergency
      departments, including satisfaction with the ESI, usefulness of the ESI compared
      with other triage algorithms, and lessons learned from implementation. METHODS: A
      self-administered questionnaire was sent to 935 people who requested the ESI
      training materials from the Agency for Healthcare Research and Quality (AHRQ) at
      the U.S. Department of Health and Human Services and who volunteered to
      participate in a study about the ESI. The response rate for the survey was 42% (n
      = 392). Telephone interviews were conducted with an additional 19 ED
      professionals. Descriptive statistics and qualitative content analysis were used
      in the data analysis. RESULTS: Three hundred twenty-two survey respondents (82%)
      reported that they use the ESI in their emergency department. Satisfaction with
      the ESI triage algorithm is high. ESI users indicated that the ESI is more
      accurate than other triage algorithms and that its strengths are simplicity of
      use and the ability to reduce the subjectivity of triage. DISCUSSION: The
      majority of ED professionals who reported using the ESI were very satisfied with
      the tool. Users found that it was more accurate than other triage algorithms and
      reduced the subjectivity of the triage process. Both survey and interview
      findings indicated that few emergency departments have formally assessed the
      impact of the ESI on ED operations.

PMID- 22401617
TI  - Practical strategies for death notification in the emergency department.

PMID- 22401618
TI  - Superior vena cava syndrome.

PMID- 22401619
TI  - Early recognition of sepsis in the emergency department: an evidence-based
      project.

PMID- 22401620
TI  - Impacting care at the stretcher side: transforming the future.

PMID- 22401621
TI  - Experience talks.

PMID- 22401622
TI  - Evaluation of Greek high school teachers' knowledge in basic life support,
      automated external defibrillation, and foreign body airway obstruction:
      implications for nursing interventions.
AB  - INTRODUCTION: The aim of this study was to evaluate the theoretic knowledge of
      high school teachers regarding cardiopulmonary resuscitation, automated external
      defibrillation, and foreign body airway obstruction. METHODS: Three hundred ten
      respondents were tested prospectively by use of a scoring system. Data were
      obtained by use of a questionnaire that included 24 questions. Data were
      collected between April 9 and June 16, 2009. RESULTS: Only 21.03% of the teachers
      had ever participated in life support courses, and most of them did not possess
      adequate theoretic knowledge in the management of adult cardiac arrest or foreign
      body airway obstruction. As the age of the teachers increases, the ratio of
      correct answers decreases. Life support course attendance has a positive effect
      on their theoretic knowledge. The majority of the teachers would welcome an
      emergency nurse to educate them and their students on basic life support and
      foreign body airway obstruction. DISCUSSION: This study shows that most of the
      respondents had a mediocre level of knowledge in basic life support, automated
      external defibrillation, and foreign body airway obstruction. Given that
      emergency nurses regularly practice resuscitation in the emergency department in
      which they are working, they have the motivation to be kept updated with the
      current guidelines on resuscitation, because guidelines on resuscitation are
      revised every 5 years. Teachers, on the other hand, are less motivated to be kept
      updated; thus emergency nurses may be the key component in educating teachers and
      school students. Therefore we believe that emergency nurses should take on the
      responsibility and act as school educators regarding cardiopulmonary
      resuscitation.

PMID- 22401623
TI  - Engaging student nurses in mock codes.

PMID- 22401625
TI  - Comparative genomics reveals evidence of marine adaptation in Salinispora
      species.
AB  - BACKGROUND: Actinobacteria represent a consistent component of most marine
      bacterial communities yet little is known about the mechanisms by which these
      Gram-positive bacteria adapt to life in the marine environment. Here we employed
      a phylogenomic approach to identify marine adaptation genes in marine
      Actinobacteria. The focus was on the obligate marine actinomycete genus
      Salinispora and the identification of marine adaptation genes that have been
      acquired from other marine bacteria. RESULTS: Functional annotation, comparative
      genomics, and evidence of a shared evolutionary history with bacteria from
      hyperosmotic environments were used to identify a pool of more than 50 marine
      adaptation genes. An Actinobacterial species tree was used to infer the
      likelihood of gene gain or loss in accounting for the distribution of each gene.
      Acquired marine adaptation genes were associated with electron transport, sodium
      and ABC transporters, and channels and pores. In addition, the loss of a
      mechanosensitive channel gene appears to have played a major role in the
      inability of Salinispora strains to grow following transfer to low osmotic
      strength media. CONCLUSIONS: The marine Actinobacteria for which genome sequences
      are available are broadly distributed throughout the Actinobacterial phylogenetic
      tree and closely related to non-marine forms suggesting they have been
      independently introduced relatively recently into the marine environment. It
      appears that the acquisition of transporters in Salinispora spp. represents a
      major marine adaptation while gene loss is proposed to play a role in the
      inability of this genus to survive outside of the marine environment. This study
      reveals fundamental differences between marine adaptations in Gram-positive and
      Gram-negative bacteria and no common genetic basis for marine adaptation among
      the Actinobacteria analyzed.

PMID- 22401626
TI  - Gene-modified lymphocytes: from caution to promise for effective cancer
      immunotherapy.

PMID- 22401627
TI  - 'Functional cure' of HIV infection: the role of immunotherapy.

PMID- 22401628
TI  - Over the fence or through the gate: how viruses infect polarized cells.

PMID- 22401630
TI  - Conference scene: progress with promising human antibodies.
AB  - Antibodies and antibody-based therapeutics have become big business, with annual
      sales over US$50 billion, accounting for >6% of worldwide pharmaceutical
      revenues. Ten molecules have blockbuster status (>US$1 billion), with six
      generating more than US$6 billion in sales. In excess of 300 products based on
      this rapidly maturing technology are in clinical trials. The generation and
      manufacture of human antibodies is now routine, although the cost of goods
      remains an issue. Optimizing combinations of antibodies with other therapeutics
      (e.g., chemotherapy) is a major short-term goal, while target validation and
      product differentiation remain significant hurdles if growth is to continue. Some
      of the notable highlights of the recent 16th International Conference on Human
      Antibodies and Hybridomas meeting in Cannes, France are described below. The
      conference was sponsored by the international journal Human Antibodies, in
      association with the Integrative Medical Sciences Association (IMSA). The Program
      Chairman was Professor Mark Glassy, IMSA, San Diego, CA, USA.

PMID- 22401631
TI  - Conference scene: shining lights on the future of autoimmunity in Asia.
AB  - The Congress on Autoimmunity was held, as was the previous 4th Asian Congress on
      Autoimmunity meeting, in Suntec City, Singapore, on 17-19 November 2011. The
      congress saw the participation of prestigious experts within the fields of
      autoimmunity, immunology, rheumatology, cardiovascular diseases and diabetology,
      with the enlightening concepts discussed briefly summarized herein. The Honorary
      President of the congress, Yehuda Shoenfeld, together with the local and
      international organizing committees, successfully put together an attractive
      scientific program with topics including the most up-to-date achievements and
      discoveries in all aspects of autoimmunity. In the surrounding of a beautiful
      city, autoimmunity was untangled, and novel, brilliant ideas emerged that could
      help to solve this fascinating conundrum.

PMID- 22401632
TI  - The effect of routine rotavirus vaccination on healthcare utilization for
      diarrhea in US children.
AB  - Cortes et al. thoroughly analyzed the effect of the introduction of mass
      rotavirus vaccination on healthcare utilization in a population of approximately
      2 million US children under 5 years of age. According to the results of the
      study, hospitalization has been reduced from prevaccination periods by 89% for
      rotavirus diarrhea and by 44% for diarrheal disease. The estimated reduction of
      hospitalizations during the two (single-year) periods amounted to 64,855 and the
      respective savings in treatment costs were US$278 million. The significance of
      this paper is its approach to the estimation of vaccine efficacy by the
      assessment of vaccination coverage and hospitalization, as well as emergency
      department and outpatient visits in a large population of children without any
      'selection' (e.g., hospitalization) bias.

PMID- 22401633
TI  - Clinical validation of sublingual formulations of Immunoxel (Dzherelo) as an
      adjuvant immunotherapy in treatment of TB patients.
AB  - Immunoxel (Dzherelo) is a water-alcohol extract of medicinal plants used in
      Ukraine as an adjunct immunotherapy to TB and HIV therapy. Four types of solid
      sublingual formulations of Immunoxel were made: sugar dragees, sugar-coated
      pills, gelatin pastilles and dried-honey lozenges. They were administered once
      daily along with TB drugs. After 1 month, 84.1% of TB patients became sputum
      negative with rates in individual groups of 89.5, 70, 76.9 and 100%,
      respectively. The conversion rate was independent of bodyweight, age, gender,
      differences in chemotherapy regimens or whether subjects had newly diagnosed TB,
      re-treated TB, multidrug-resistant TB or TB with HIV coinfection. Patients
      experienced earlier clinical improvement, faster defervescence, weight gain, a
      higher hemoglobin content and reduced inflammation as evidenced by lower
      leukocyte counts and erythrocyte sedimentation rate. By contrast, in the placebo
      group, only 19% of patients had converted. These findings imply that mucosal
      delivery of solid Immunoxel is equivalent to the original liquid formula given
      per os twice-daily for 2-4 months.

PMID- 22401634
TI  - Cellular immunotherapy for soft tissue sarcomas.
AB  - Soft tissue sarcomas are rare neoplasms, with approximately 9000 new cases in the
      USA every year. Unfortunately, during the past two decades, there has been little
      progress in the treatment of metastatic soft tissue sarcomas beyond the standard
      approaches of surgery, chemotherapy and radiation. Immunotherapy is a modality
      complementary to conventional therapy. It is appealing because functional
      antitumor activity could affect both local-regional and systemic disease, and act
      over a prolonged period of time. In this report, we review immunotherapeutic
      investigative strategies that are being developed, including several tumor
      vaccine, antigen vaccine and dendritic cell vaccine strategies.

PMID- 22401636
TI  - Safety of allergen immunotherapy: a review of premedication and dose adjustment.
AB  - From the first allergen immunotherapy proposed in the early 1900s to the present
      day, numerous studies have proven the efficacy of allergen immunotherapy for the
      treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma and
      stinging insect hypersensitivity. The major risk, however small, with allergen
      immunotherapy is anaphylaxis. There has been considerable interest and debate
      regarding risk factors for immunotherapy reactions (local and systemic) and
      interventions to reduce the occurrence of these reactions. One of these
      interventions that is especially debated regards dose adjustment for various
      reasons, but in particular for local reactions. In this review, we discuss the
      safety of immunotherapy and provide a comprehensive review of the literature
      regarding immunotherapy schedules and doses.

PMID- 22401637
TI  - Immunotherapy for acute kidney injury.
AB  - Acute renal failure, now referred to as acute kidney injury, is a common and
      clinically important problem. Acute kidney injury frequently occurs as a result
      of acute tubular necrosis (ATN), which is often caused by a reduction in systemic
      blood pressure or renal blood flow (e.g., as observed in severe sepsis or during
      renal transplantation). The disease course in ATN is variable, including
      prolonged dialysis-dependence and chronic renal dysfunction, but there is
      currently no specific therapy for ATN. There is increasing evidence that the
      inflammatory response in ATN significantly contributes to disease severity and
      outcome. In this review, we summarize recent developments in the understanding of
      how the immune system responds to dying cells, and the relevance of these
      discoveries to ATN. In particular, NLRP3 inflammasome activation and IL-1beta
      mediated neutrophil recruitment are likely to play a key role and may provide
      novel therapeutic targets for immunotherapy in ATN.

PMID- 22401635
TI  - Myeloid suppressor cells and immune modulation in lung cancer.
AB  - Many tumors, including lung cancers, promote immune tolerance to escape host
      immune surveillance and facilitate tumor growth. Tumors utilize numerous pathways
      to inhibit immune responses, including the elaboration of immune-suppressive
      mediators such as PGE2, TGF-beta, IL-10, VEGF, GM-CSF, IL-6, S100A8/A9 and SCF,
      which recruit and/or activate myeloid-derived suppressor cells (MDSCs). MDSCs, a
      subset of heterogeneous bone marrow-derived hematopoietic cells, are found in the
      peripheral blood of cancer patients and positively correlate to malignancy. Solid
      tumors contain MDSCs that maintain an immune-suppressive network in the tumor
      microenvironment. This review will focus on the interaction of tumors with MDSCs
      that lead to dysregulation of antigen presentation and T-cell activities in
      murine tumor models. Specific genetic signatures in lung cancer modulate the
      activities of MDSCs and impact tumor progression. Targeting MDSCs may have a long
      term antitumor benefit and is at the forefront of anticancer therapeutic
      strategies.

PMID- 22401638
TI  - Predicting the clinical efficacy and potential adverse effects of a humanized
      anticocaine monoclonal antibody.
AB  - The effects of a humanized monoclonal antibody (mAb) having high affinity and
      specificity for cocaine in animal models are reviewed. The mAb reduced the
      concentration of cocaine in the brain of mice after intravenous injection of
      cocaine. In addition, the mAb increased the concentration of cocaine required to
      reinstate cocaine self-administration. These effects may predict clinical
      efficacy of a passive immunotherapy for reducing the probability of cocaine
      induced relapse. However, in the presence of the mAb, once cocaine self
      administration was reinstated, the consumption rate of cocaine was increased.
      This effect is hypothesized to result from a pharmacokinetic/pharmacodynamic
      interaction. A humanized mAb should minimize adverse events related to the
      immunogenicity of the mAb protein, and the specificity for cocaine should avoid
      adverse events related to interactions with physiologically relevant endogenous
      proteins.

PMID- 22401640
TI  - The critical role of imaging navigation and guidance in transcatheter aortic
      valve implantation.

PMID- 22401642
TI  - Steady-state plasma concentration profile of transdermal rotigotine: an
      integrated analysis of three, open-label, randomized, phase I multiple dose
      studies.
AB  - BACKGROUND: The dopamine agonist rotigotine is formulated in a transdermal
      delivery system (patch) for once-daily application. It has been reported as
      efficacious in the treatment of idiopathic Parkinson's disease (PD) and restless
      legs syndrome. OBJECTIVE: This article summarizes the results of 3 clinical
      studies conducted to characterize the 24-hour pharmacokinetic profile of
      rotigotine in steady state and the effect of different patch application sites on
      this profile. In addition, the relative bioavailability of a single, large patch
      versus 2 smaller patches was assessed. METHODS: One Phase I study (SP871)
      assessed the steady-state pharmacokinetic properties at different application
      sites at a rotigotine maintenance dose of 3 mg/24 hours in healthy participants.
      Due to tolerability issues, the steady-state pharmacokinetic properties of
      rotigotine at higher doses (8 mg/24 hours) was assessed in 2 Phase I studies
      (SP630, SP651) in early-stage PD patients. Relative rotigotine bioavailability
      from a 40 cm(2) patch versus 2 * 20 cm(2) patches (SP651) and from a 15 cm(2)
      patch versus 1 * 5 cm(2) + 1 * 10 cm(2) patches (SP871) was also evaluated.
      Rotigotine concentrations in plasma were analyzed using a validated LC-MS/MS
      method. The pharmacokinetic variables were calculated using standard
      noncompartmental analysis. RESULTS: Release of rotigotine to the skin was 31% to
      62% of total drug content in the patch. Variability of rotigotine exposure was
      low within participants (15%) compared with the variability observed between
      participants (54%). Rotigotine exposure increased proportionally in the
      therapeutic dose range of 2 mg/24 hours to 8 mg/24 hours. Plasma concentrations
      at steady state were stable over the 24-hour patch-on period. Delivery via a
      single, large patch compared with a combination of smaller patches did not appear
      to influence exposure to rotigotine. Bioavailability showed some variability
      depending on patch application site (hip, shoulder, abdomen, flank, thigh, upper
      arm); the respective mean ratios for AUC ranged between 0.87 (abdomen vs flank)
      and 1.46 (shoulder vs thigh). CONCLUSIONS: Continuous rotigotine delivery via a
      once-daily transdermal patch generated stable mean steady-state 24-hour plasma
      concentrations in healthy participants as well as patients with early-stage PD.
      Doses were achieved either by application of 1 large patch or a combination of
      smaller patches, resulting in the same total surface area.

PMID- 22401641
TI  - Catalytic peroxynitrite decomposition improves reperfusion injury after heart
      transplantation.
AB  - OBJECTIVE: Peroxynitrite, a reactive nitrogen species, has been implicated in the
      development of ischemia-reperfusion injury. The present study investigated the
      effects of the potent peroxynitrite decomposition catalyst FP15 on myocardial and
      endothelial function after hypothermic ischemia-reperfusion in a heterotopic rat
      heart transplantation model. METHODS: After a 1-hour ischemic preservation and
      implantation of donor hearts, reperfusion was started after application of
      vehicle (5% glucose solution) or FP15 (0.3 mg/kg). The assessment of left
      ventricular pressure-volume relations, total coronary blood flow, endothelial
      function, immunohistochemical markers of nitro-oxidative stress, and myocardial
      high-energy phosphates was performed at 1 and 24 hours of reperfusion. RESULTS:
      After 1 hour of reperfusion, myocardial contractility (maximal slope of systolic
      pressure increment at 140 MUL left ventricular volume: 5435 +/- 508 mm Hg/s vs
      2346 +/- 263 mm Hg/s), coronary blood flow (3.98 +/- 0.33 mL/min/g vs 2.74 +/-
      0.29 mL/min/g), and endothelial function were significantly improved, nitro
      oxidative stress was reduced, and myocardial high-energy phosphate content was
      preserved in the FP15-treated animals compared with controls. CONCLUSIONS:
      Pharmacologic peroxynitrite decomposition reduces reperfusion injury after heart
      transplantation as the result of reduction of nitro-oxidative stress and
      prevention of energy depletion and exerts a beneficial effect against reperfusion
      induced graft cardiac and coronary endothelial dysfunction.

PMID- 22401643
TI  - Immunomodulatory drugs in multiple myeloma: from molecular mechanisms of action
      to clinical practice.
AB  - Multiple myeloma (MM) is a clonal disorder of plasma cells that is considered
      incurable using the currently available treatments. Cytogenetic, molecular and
      proteonomic techniques have contributed toward a better understanding of the
      pathophysiology and prognostic factors of this heterogeneous malignancy, whose
      management has rapidly evolved over the years. The introduction of thalidomide,
      and the development of safer and more effective thalidomide analogues, represents
      the major therapeutic advances. Thalidomide, initially used in the treatment of
      MM because of its angiogenic properties, has considerable therapeutic activity
      (alone or in combination with other drugs) at all stages of the disease. However,
      a number of new analogues, such as lenalidomide and pomalidomide, have been
      developed and are known as "immunomodulatory drugs" (IMIDs). Although they are
      analogues of thalidomide, they have direct anti-tumor properties, a better
      tolerability profile and specific activity in both relapsing refractory MM and
      newly diagnosed disease. The mechanisms of action of IMIDs are still being
      investigated, but recent studies suggest that, in addition to their anti
      angiogenic activity, they have anti-inflammatory and immunomodulatory properties,
      and directly and indirectly target tumor activity by interfering with various
      components of the bone marrow (BM) micro-environment. In this paper, we review
      the pharmacology, mechanisms of action, pre-clinical and clinical efficacy, and
      the current status of IMIDs in the treatment of MM.

PMID- 22401644
TI  - Medical end-of-life decisions: does its use differ in vulnerable patient groups?
      A systematic review and meta-analysis.
AB  - Medical end-of-life decisions, defined as end-of-life practices with a potential
      or certain life-shortening effect, precede almost 50% of deaths in Western
      countries, and receive ample medical-ethical attention. This systematic review
      aims to detect whether there are differences in the prevalence of medical end-of
      life decisions in 'vulnerable' patient groups. In 2009, five major databases were
      scrutinized for publications containing original data on the prevalence of
      euthanasia/physician-assisted suicide, life-ending without explicit patient
      request, intensified symptom alleviation, non-treatment decisions and palliative
      sedation by social factors (eg age, gender and SES). Heterogeneous findings were
      pooled using a random effects model. We identified 6377 papers of which 51 papers
      were selected, involving over 1.09 million patients. Most publications reported
      the prevalence of non-treatment decisions. The most studied social factors were
      age and gender. Among patients older than eighty years, non-treatment decisions
      occurred more frequently compared with younger patients, while intensified
      symptom alleviation, palliative sedation, euthanasia/physician-assisted suicide
      and life-ending without explicit request were practiced less often. Similar
      patterns of association, although less strong, were found for female patients
      compared with males and those with lower levels of education versus more highly
      educated patients. We conclude that the administration of medication with a
      potential or certain life-shortening effect seemed generally to be practiced less
      often among the elderly, females and less well-educated patients compared with
      younger, male or more educated patients, while decisions that include the
      withdrawal or withholding of treatments seem to be more common in these groups.
      Further studies should focus on investigating whether these differences reflect
      less than optimal end-of-life care for specific patient groups.

PMID- 22401645
TI  - Vaginal practices as women's agency in sub-Saharan Africa: a synthesis of meaning
      and motivation through meta-ethnography.
AB  - This paper reports on a systematic review of qualitative research about vaginal
      practices in sub-Saharan Africa, which used meta-ethnographic methods to
      understand their origins, their meanings for the women who use them, and how they
      have evolved in time and place. We included published documents which were based
      on qualitative methods of data collection and analysis and contained information
      on vaginal practices. After screening, 16 texts were included which dated from
      1951 to 2008. We found that practices evolve and adapt to present circumstances
      and that they remain an important source of power for women to negotiate
      challenges that they face. Recent evidence suggests that some practices may
      increase a woman's susceptibility to HIV and other sexually transmitted
      infections. The success of new female-controlled prevention technologies, such as
      microbicides, might be determined by whether they can and will be used by women
      in the course of their daily life.

PMID- 22401646
TI  - Adapting the minority stress model: associations between gender non-conformity
      stigma, HIV-related stigma and depression among men who have sex with men in
      South India.
AB  - Marginalization and stigmatization heighten the vulnerability of sexual
      minorities to inequitable mental health outcomes. There is a dearth of
      information regarding stigma and mental health among men who have sex with men
      (MSM) in India. We adapted Meyer's minority stress model to explore associations
      between stigma and depression among MSM in South India. The study objective was
      to examine the influence of sexual stigma, gender non-conformity stigma (GNS) and
      HIV-related stigma (HIV-S) on depression among MSM in South India. A cross
      sectional survey was administered to MSM in urban (Chennai) (n=100) and semi
      urban (Kumbakonam) (n=100) locations in Tamil Nadu. The majority of participants
      reported moderate/severe depression scores. Participants in Chennai reported
      significantly higher levels of GNS, social support and resilient coping, and
      lower levels of HIV-S and depression, than participants in Kumbakonam.
      Hierarchical block regression analyses were conducted to measure associations
      between independent (GNS, HIV-S), moderator (social support, resilient coping)
      and dependent (depression) variables. Sexual stigma was not included in
      regression analyses due to multicollinearity with GNS. The first regression
      analyses assessed associations between depression and stigma subtypes. In
      Chennai, perceived GNS was associated with depression; in Kumbakonam
      enacted/perceived GNS and vicarious HIV-S were associated with depression. In the
      moderation analyses, overall GNS and HIV-S scores (subtypes combined) accounted
      for a significant amount of variability in depression in both locations, although
      HIV-S was only a significant predictor in Kumbakonam. Social support and
      resilient coping were associated with lower depression but did not moderate the
      influence of HIV-S or GNS on depression. Differences in stigma, coping, social
      support and depression between locations highlight the salience of considering
      geographical context in stigma analyses. Associations between HIV-S and
      depression among HIV-negative MSM emphasize the significance of symbolic stigma.
      Findings may inform multi-level stigma reduction and health promotion
      interventions with MSM in South India.

PMID- 22401647
TI  - 'On the street where you live': Neighbourhood deprivation and quality of life
      among community-dwelling older people in Edinburgh, Scotland.
AB  - It is well established that neighbourhood quality is related to various aspects
      of people's health and coping, especially in old age. There have also been a few
      reports on the links between self-reported neighbourhood quality and quality of
      life in older age. However, it is not clear which aspects of quality of life in
      particular are related to neighbourhood quality and whether these associations
      are independent of the roles of cognitive, socioeconomic or health status, or
      rating biases. Using a large sample of Scots from the Edinburgh area (N = 1091,
      of whom 548 were men) aged between 68 and 71 years, this study shows direct
      associations of objectively and comprehensively determined neighbourhood
      deprivation with self-perceived quality of life in physical and environmental
      domains, but not in psychological or social relationship domains. In a path
      model, these associations were independent of the roles of childhood cognitive
      ability and change in it to age 70, educational attainment, and occupational
      social class. The count of adverse health conditions (cardiovascular disease,
      stroke history, high blood pressure, diabetes, or arthritis) was associated with
      both quality of life and neighbourhood deprivation, and mediated the indirect
      links from neighbourhood deprivation to physical, psychological and environmental
      domains of quality of life. It is concluded that the neighbourhood in which older
      people live plays a role in one of the most important outcomes-how satisfied they
      are with various aspects of their life including physical functioning.

PMID- 22401648
TI  - Does the association between smoking and mortality differ by educational level?
AB  - Some researchers suggest that the effect of smoking on health depends on
      socioeconomic status; while others purport that the effect of smoking on health
      is similar across all social groups. This question of the interaction between
      smoking and socioeconomic status is important to an improved understanding of the
      role of smoking in the social gradient in mortality and morbidity. For this
      purpose, we examined whether educational level modifies the association between
      smoking and mortality. Information on smoking by age, gender and educational
      level was extracted from the Belgian Health Interview Surveys of 1997 and 2001.
      The mortality follow up of the survey respondents was reported until December
      2010. A Poisson regression was used to estimate the hazard ratio of mortality for
      heavy smokers, light smokers, and former smokers compared with never smokers by
      educational level controlling for age and other confounders. Among men, we found
      lower hazard ratios in the lowest educational category compared with the
      intermediate and high-educated categories. For instance, for heavy smokers, the
      hazard ratios were 2.59 (1.18-5.70) for those with low levels of education, 4.03
      (2.59-6.26) for those with intermediate levels of education and 3.78 (1.52-9.43)
      for the highly educated. However, the interaction between smoking and education
      was not statistically significant. For women, the hazard ratios were not
      significant for any educational category except for heavy smokers with
      intermediate levels of education. Also here the interaction was not statistically
      significant. Our results support the hypothesis that educational attainment does
      not substantially influence the association between smoking and mortality.

PMID- 22401649
TI  - Asthma control test (ACT): comparison with clinical, functional, and biological
      markers of asthma control.
AB  - BACKGROUND: Asthma Control Test (ACT) is a simple tool for assessing the level of
      asthma control in clinical practice, and it has been validated in comparison with
      a general clinical assessment of asthma control, including forced expiratory
      volume in the first second (FEV(1)). OBJECTIVE: To evaluate the relationship
      between ACT score and clinical and functional findings of asthma control and
      biomarkers of airway inflammation. METHODS: A total of 68 asthmatic patients
      observed in our asthma clinic (33 regularly treated with inhaled corticosteroids
      (ICS) and 35 ICS-naive) filled ACT questionnaire and underwent the following
      measurements: (a) FEV(1) before and after salbutamol; (b) exhaled nitric oxide;
      (c) bronchial hyperresponsiveness to methacholine; (d) sputum eosinophil count;
      and (e) daytime and nighttime symptoms, rescue salbutamol, and twice-daily peak
      expiratory flow (PEF) recording on a 4-week diary card. RESULTS: ACT score
      significantly correlated with symptom score, rescue medication use, and PEF
      variability, but not with FEV(1), FEV(1) reversibility, and markers of airway
      inflammation, which could not distinguish controlled from uncontrolled patients
      according to ACT, regardless of ICS treatment. CONCLUSION: ACT score is a valid
      tool to simply assess the current level of asthma control in terms of symptoms,
      rescue medication use, and PEF variability. Pulmonary function and biomarkers of
      airway inflammation are not related to the clinical asthma control as assessed by
      ACT and may represent additional measurements potentially useful in asthma
      management.

PMID- 22401650
TI  - Nanocomposites of ZnS and poly-(dimethyl)-block-(phenyl)siloxane as a new high
      refractive-index polymer media.
AB  - In the present paper, we describe a new and original method to obtain
      transparent, siloxane-based composites, with high refractive index (up to 1.68).
      The method is based on the decomposition of Zn-siloxane, mixed with a poly
      (dimethyl)-block-(phenyl)siloxane matrix in different ratios. It was found that
      after treatment of such mixed metal-containing polymer blend with H2S, the
      nanoparticles of ZnS are formed, with the size in a 1- to 5-nm range, which allow
      effective increase of the refractive index of the nanocomposite mixture with poly
      (dimethyl)-block-(phenyl)siloxane without loss of film transparency. We succeded
      to increase the refractive index from 1.54 (pure matrix) up to 1.68 (composite
      with a ZnS content of 4.6 vol.%). The siloxane-based compositions are optically
      transparent, which makes it possible to use them as light-emitting diodes or
      solar cell sealants or adhesives.

PMID- 22401651
TI  - Probing for a leaving group effect on the generation and reactivity of phenyl
      cations.
AB  - Phenyl cations are smoothly generated by the photoheterolytic cleavage of an Ar
      LG bond (LG = leaving group). With the aim of evaluating the scope of the method,
      a series of 4-methoxy-2-(trimethylsilyl)phenyl derivatives (sulfonic, LG =
      MeSO(3) and CF(3)SO(3), phosphate, LG = (EtO)(2)(O)PO esters and the
      corresponding chloride) have been compared as probes for evaluating the leaving
      group ability. The photocleavage was a general reaction, with the somewhat
      surprising order (EtO)(2)(O)PO ~ Cl > CF(3)SO(3) > MeSO(3) (Phi = 0.50 to 0.16 in
      CF(3)CH(2)OH and lower values in MeCN-H(2)O). The ensuing reactions did not
      depend on the LGs but only on the structure of the phenyl cation (the silyl group
      tuned the triplet to singlet intersystem crossing and the electrophilicity) and
      on the medium (formation of a complex with water slowed the electrophilic
      reactions).

PMID- 22401652
TI  - Open-label evaluation of the skin-brightening efficacy of a skin-brightening
      system using decapeptide-12.
AB  - This prospective study evaluated the safety and efficacy of decapeptide-12 in
      conjunction with an antioxidant cleanser, glycolic-acid containing facial
      moisturizer and broad-spectrum sunscreen in the treatment of facial
      hyperpigmentation associated with chronic photodamage. Fifteen female subjects
      with Fitzpatrick skin types I through IV and documented photodamage were entered
      into the study, of whom 13 completed the study. Results were obtained at weeks 4,
      8, 12, 18 and 24 and were assessed by both volunteers and investigators based on
      standardised digital photography using the Global Assessment of Photodamage
      Severity Scale. At the conclusion of the study at 24 weeks, 38.5% of the
      volunteers achieved complete clearance from a moderate (grade 3) degree of
      photodamage at baseline to completely cleared (grade 1). Another 30.7% improved
      from a moderate (grade 3) degree of photodamage at baseline to a mild (grade 2)
      degree of photodamage. An additional 15.4% improved from a severe (grade 4)
      degree of photodamage at baseline to a moderate (grade 3) degree of photodamage
      while an equal 15.4% improved from a severe (grade 4) degree of photodamage at
      baseline to a designation of mild (grade 2) at 24 weeks. All study-related
      treatments were well tolerated. The mechanism of action of decapeptide-12
      includes inhibition of melanin synthesis via inhibition of the tyrosinase enzyme.
      Advantages of decapeptide-12 over other skin-brightening agents include its low
      incidence of side effects, lack of cytotoxicity and safe use in ethnic skin as
      well as in patients who have failed other treatment regimens.

PMID- 22401654
TI  - Optimizing high-throughput metabolomic biomarker screening: a study of quenching
      solutions to freeze intracellular metabolism in CHO cells.
AB  - Metabolomics is a rapidly emerging tool for studying and optimizing both media
      and bioprocess development for culturing recombinant mammalian cells that are
      used in protein production processes. Quenching of the cells is crucial to fix
      their metabolic status at the time of sampling. Three precooled quenching
      solutions were tested for their ability to fix the metabolic activity of CHO
      cells: phosphate-buffered saline (PBS) (pH 7.4; 0.5 degrees C), 60% methanol with
      70 mM HEPES (pH 7.4; -20 degrees C), and 60% methanol with 0.85% (w/v) ammonium
      bicarbonate (AMBIC) (pH 7.4; -20 degrees C). The metabolic activity of the
      sampled CHO cells was assessed by determining the intracellular levels of ATP
      using a bioluminescence assay and selected metabolites with LC-MS/MS. We found
      the precooled PBS (pH 7.4; 0.5 degrees C) to be the optimal quenching reagent for
      fixing intracellular metabolism. Importantly, the structural integrity of the
      cell membrane was maintained and highest yields were obtained for intracellular
      levels of ATP as well as for 18 out of 28 intracellular metabolites. In contrast
      to the previously reported studies, buffered methanol quenching was not
      applicable for suspension cultured CHO cells as cellular membrane integrity was
      affected. We recommend that the cells are quenched and washed simultaneously to
      keep the sampling time to a minimum and to prevent any further metabolic activity
      in the cells. We observed that additional washing steps are not required. Our
      analyses suggest that methanol as quenching solution, even in combination with a
      buffer substance, appears not suitable for quenching sensitive mammalian cells.
      The protocol we report herein is a simple cell sampling method that enables high
      throughput metabolomic analyses and is suitable for a large number of samples.

PMID- 22401653
TI  - A structural analysis of glycosaminoglycans from lethal and nonlethal breast
      cancer tissues: toward a novel class of theragnostics for personalized medicine
      in oncology?
AB  - Cancer is one of the leading noncommunicable diseases that vastly impacts both
      developed and developing countries. Truly innovative diagnostics that inform
      disease susceptibility, prognosis, and/or response to treatment (theragnostics)
      are seriously needed for global public health and personalized medicine for
      patients with cancer. This study examined the structure and content of
      glycosaminoglycans (GAGs) in lethal and nonlethal breast cancer tissues from six
      patients. The glycosaminoglycan content isolated from tissue containing lethal
      cancer tumors was approximately twice that of other tissues. Molecular weight
      analysis showed that glycosaminoglycans from cancerous tissue had a longer weight
      average chain length by an average of five disaccharide units, an increase of
      approximately 15%. Dissacharide analysis found differences in sulfation patterns
      between cancerous and normal tissues, as well as sulfation differences in GAG
      chains isolated from patients with lethal and nonlethal cancer. Specifically,
      cancerous tissue showed an increase in sulfation at the "6S" position of CS
      chains and an increase in the levels of the HS disaccharide NSCS. Patients with
      lethal cancer showed a decrease in HS sulfation, with lower levels of "6S" and
      higher levels of the unsulfated "0S" disaccharide. Although these findings come
      from a limited sample size, they indicate that structural changes in GAGs exist
      between cancerous and noncancerous tissues and between tissues from patients with
      highly metastatic cancer and cancer that was successfully treated by
      chemotherapy. Based on these findings, we hypothesize that (1) there are putative
      changes in the body's construction of GAGs as tissue becomes cancerous; (2) there
      may be innate structural person-to-person variations in GAG composition that
      facilitate the metastasis of tumors in some patients when they develop cancer.

PMID- 22401655
TI  - Hypoxia affects mitochondrial protein expression in rat skeletal muscle.
AB  - Hypoxia affects mammalian mitochondrial function, as well as mitochondria-based
      energy metabolism. The detail mechanism has not been fully understood. In this
      study, we detected protein expression levels in mitochondrial fractions of Wistar
      rats exposed to hypobaric hypoxia by use of proteomic methods. Adult male Wistar
      rats were randomized into an hypoxic (4,500 m, 30 days) group and a normoxic
      control group (sea level). Gastrocnemius muscles mitochondria were extracted and
      purified. Mitochondrial oxygen consumption was measured with a Clark oxygen
      electrode; mitochondrial transmembrane potential was detected with Rhodamine 123
      as a fluoresce probe. Using 2-DE and MALDI-TOF MS analysis, we identified eight
      mitochondrial protein spots that were differentially expressed in the hypoxic
      group compared with the normoxic control. These proteins included Chain A of F1
      ATPase, voltage dependent anion channel 1 (VDAC), hydroxyacyl Coenzyme A
      dehydrogenase alpha-subunit, mitochondrial F1 complex gamma-subunit, androgen
      regulated protein and tripartite motif protein 50. Two of the spots, VDAC and ATP
      synthase alpha-subunit, were confirmed by Western blotting analysis. Oxygen
      consumption during State 3 respiration, as well as the respiratory control ratio
      (RCR) was significantly higher in the control than that in the hypoxic group;
      mitochondrial transmembrane potential was significantly higher in hypoxic group
      than that in the control. With successful use of multiple proteomic analysis
      techniques, we demonstrates that 30 days hypoxia exposure has effects on the
      expression of mitochondrial proteins involved in ATP production and lipid
      metabolism, decrease the stability of mitochondrial membrane, and affect the
      mitochondrial electron transport chain.

PMID- 22401656
TI  - Molecular pathways and crosstalk characterizing the cardiorenal syndrome.
AB  - The risk of developing cardiovascular diseases (CVD) is dramatically increased in
      patients with chronic kidney diseases (CKD). Mechanisms leading to this
      cardiorenal syndrome (CRS) are multifactorial, and combined analyses of both
      failing organs may provide routes toward developing strategies for early risk
      assessment, prognosis, and consequently effective therapy. In order to identify
      molecular mechanisms involved in the crosstalk between the diseased
      cardiovascular system and kidney, we analyzed tissue specific transcriptomics
      profiles on atherosclerosis and diabetic nephropathy together with gene sets
      associated with cardiovascular and chronic kidney diseases that derived from a
      literature mining approach. We focused on enriched molecular pathways and
      highlight molecular interactions found within as well as between affected
      pathways identified for the two organs. Analysis on the level of molecular
      pathways pointed out the role of PPAR signaling, coagulation, inflammation, and
      focal adhesion pathways in formation and progression of the CRS. The proteins
      apolipoprotein A1 (APOA1) and albumin (ALB) turned out to be of particular
      importance in the context of dyslipidemia, one of the major risk factors for the
      development of CVD. In summary, our analyses highlight mechanisms associated with
      dyslipidemia, hemodynamic regulation, and inflammation on the interface between
      the cardiovascular and the renal system.

PMID- 22401657
TI  - Enhancing diagnosis, prognosis, and therapeutic outcome prediction of gliomas
      using genomics.
AB  - Malignant gliomas are the most frequent type of primary brain tumors. Patients'
      outcome has not improved despite new therapeutics, thus underscoring the need for
      a better understanding of their genetics and a fresh approach to treatment. The
      lack of reproducibility in the classification of many gliomas presents an
      opportunity where genomics may be paramount for accurate diagnosis and therefore
      best for therapeutic decisions. The aim of this work is to identify large and
      focal copy number abnormalities (CNA) and loss of heterozygosity (LOH) events in
      a malignant glioma population. We hypothesized that these explorations will allow
      discovery of genetic markers that may improve diagnosis and predict outcome. DNA
      from glioma specimens were subjected to CNA and LOH analyses. Our studies
      revealed more than 4000 CNA and several LOH loci. Losses of chromosomes 1p and/or
      19q, 10, 13, 14, and 22 and gains of 7, 19, and 20 were found. Several of these
      alterations correlated significantly with histology and grade. Further, LOH was
      detected at numerous chromosomes. Interestingly, several of these loci harbor
      genes with potential or reported tumor suppressor properties. These novel genetic
      signatures may lead to critical insights into diagnosis, classification,
      prognosis, and design of individualized therapies.

PMID- 22401658
TI  - Global transcriptional profiling in porcine mammary glands from late pregnancy to
      peak lactation.
AB  - Sow milk yield and quality is crucial for the survival and growth of piglets. To
      understand the molecular mechanisms of lactogenesis and lactation, mammary tissue
      samples were taken from six sows at -17(+/-2), 1 and 17(+/-2) days relative to
      parturition. Mammary tissues from two sows in the same stage were used to extract
      RNA, which were subsequently pooled in equal amounts. Nine pooled samples were
      hybridized to porcine Affymetrix GeneChips. Totally 1,524 genes were detected as
      significantly differentially expressed over the time course tested (p<0.01,
      q<0.01, fold change>=2 or <=-2), including 709 upregulated and 575 downregulated
      genes identified at peak lactation compared to late pregnancy. Gene ontology
      analysis revealed that most of the upregulated genes were involved in transport,
      biosynthetic processes, and homeostasis, whereas most of the downregulated genes
      were involved in intracellular signaling cascades, cell cycle, and DNA
      replication. Furthermore, we identified 64 differentially expressed genes of the
      solute carrier families. Taken together, our microarray analysis provides
      insights into previously uncharacterized changes in transcriptome between late
      pregnancy and peak lactation in the porcine mammary gland. The solute carrier
      genes and other differentially expressed genes identified in this study will
      guide further characterization of their function to enhance milk yield and piglet
      growth.

PMID- 22401659
TI  - Opportunities and challenges for the life sciences community.
AB  - Twenty-first century life sciences have transformed into data-enabled (also
      called data-intensive, data-driven, or big data) sciences. They principally
      depend on data-, computation-, and instrumentation-intensive approaches to seek
      comprehensive understanding of complex biological processes and systems (e.g.,
      ecosystems, complex diseases, environmental, and health challenges). Federal
      agencies including the National Science Foundation (NSF) have played and continue
      to play an exceptional leadership role by innovatively addressing the challenges
      of data-enabled life sciences. Yet even more is required not only to keep up with
      the current developments, but also to pro-actively enable future research needs.
      Straightforward access to data, computing, and analysis resources will enable
      true democratization of research competitions; thus investigators will compete
      based on the merits and broader impact of their ideas and approaches rather than
      on the scale of their institutional resources. This is the Final Report for Data
      Intensive Science Workshops DISW1 and DISW2. The first NSF-funded Data Intensive
      Science Workshop (DISW1, Seattle, WA, September 19-20, 2010) overviewed the
      status of the data-enabled life sciences and identified their challenges and
      opportunities. This served as a baseline for the second NSF-funded DIS workshop
      (DISW2, Washington, DC, May 16-17, 2011). Based on the findings of DISW2 the
      following overarching recommendation to the NSF was proposed: establish a
      community alliance to be the voice and framework of the data-enabled life
      sciences. After this Final Report was finished, Data-Enabled Life Sciences
      Alliance (DELSA, www.delsall.org ) was formed to become a Digital Commons for the
      life sciences community.

PMID- 22401660
TI  - The effect of participatory community communication on HIV preventive behaviors
      among ethnic minority youth in central Vietnam.
AB  - BACKGROUND: In Vietnam, socially marginalized groups such as ethnic minorities in
      mountainous areas are often difficult to engage in HIV research and prevention
      programs. This intervention study aimed to estimate the effect of participatory
      community communication (PCC) on changing HIV preventive ideation and behavior
      among ethnic minority youth in a rural district from central Vietnam. METHODS: In
      a cross-sectional survey after the PCC intervention, using a structured
      questionnaire, 800 ethnic minority youth were approached for face-to-face
      interviews. Propensity score matching (PSM) technique was then utilized to match
      these participants into two groups-intervention and control-for estimating the
      effect of the PCC. RESULTS: HIV preventive knowledge and ideation tended to
      increase as the level of recall changed accordingly. The campaign had a
      significant indirect effect on condom use through its effect on ideation or
      perceptions. When intervention and control group statistically equivalently
      reached in terms of individual and social characteristics by PSM, proportions of
      displaying HIV preventive knowledge, ideation and condom use were significantly
      higher in intervention group than in matched control counterparts, accounting for
      net differences of 7.4%, 12.7% and 5%, respectively, and can be translated into
      the number of 210; 361 and 142 ethnic minority youth in the population.
      CONCLUSIONS: The study informs public health implications both theoretically and
      practically to guide effective HIV control programs for marginalized communities
      in resources-constrained settings like rural Vietnam and similar contexts of
      developing countries.

PMID- 22401661
TI  - Polyamide 66 microspheres metallised with in situ synthesised gold nanoparticles
      for a catalytic application.
AB  - A simple concept is proposed to metallise polyamide 66 (PA66) spherulite
      structures with in situ synthesised gold nanoparticles (Au NPs) using a wet
      chemical method. This cost-effective approach, applied to produce a PA66/Au NP
      hybrid material, offers the advantages of controlling the nanoparticle size, the
      size distribution and the organic-inorganic interactions. These are the key
      factors that have to be controlled to construct consistent Au nanostructures
      which are essential for producing the catalytic activities of interest. The
      hybrid materials obtained are characterised by means of scanning electron
      microscopy, transmission electron microscopy, attenuated total reflection-Fourier
      transform infrared spectrometry and X-ray diffraction spectrometry. The results
      show that PA66 microspheres obtained via the crystallisation process are coated
      with Au NPs of 13 nm in size. It was found that controlling the metal
      coordination is the key parameter to template the Au NPs on the spherulite
      surfaces. The preparation processes and the key factors leading to the formation
      of PA66 spherulites coated with Au NPs are discussed. Moreover, the efficiency of
      the coated spherulites as a potential catalyst is proved by demonstrating the
      reduction of methylene blue via UV-visible spectrometry.

PMID- 22401662
TI  - A piperidine chiron for the Veratrum alkaloids.
AB  - A Veratrum piperidine chiron was prepared over 11 steps (7.9% yield) from (-)
      citronellal. Three methods for the installation of the propargylic side chain
      onto a cyclic enamide are presented.

PMID- 22401663
TI  - Improvement of microstomia in scleroderma after intense pulsed light: A case
      series of four patients.
AB  - INTRODUCTION: Intense pulsed light (IPL) treatment is well known for, for
      example, photo rejuvenation, where higher cut-off filters are used. The longer
      wavelengths penetrate deeper in the dermis leading to damage of the collagen and
      stimulation of new collagen formation, which lead to more soft and elastic skin.
      Microstomia in systemic sclerosis is the end result of excessive collagen
      deposition, which makes the perioral skin firm and tight. The patients have
      difficulties performing oral self-care, and even professional dental care can be
      complicated. METHODS: Four patients with systemic sclerosis and microstomia were
      treated with IPL (Ellipse A/S Flex System, Denmark ) in the perioral region. The
      patients received 3-5 treatments with 4-week interval. Oral opening was measured
      before and after treatments. results: The oral opening increased approximately 1
      mm per treatment in three patients. One patient had temporomandibular joint
      symptoms of locking and did not have any increase in mouth opening. All four
      patients felt softening of the perioral skin, and all four patients described
      that articulation, eating and tooth brushing had become easier. CONCLUSION: IPL
      can be a new adjunctive alternative in the non-surgical treatment of microstomia
      in patients with systemic sclerosis.

PMID- 22401664
TI  - A fluent electronic support and clinical case letters: new formats and more
      interactivity between journal of oral implantology and its readers.

PMID- 22401665
TI  - Socioeconomic inequalities in health: individual or area level; does it matter?
AB  - In the last decades we have accumulated substantial knowledge about the risk
      factors that lead to cardiovascular disease. Despite this progress, in this issue
      of BMC Public Health we learn that little improvement has been made towards
      reducing inequalities in these risk factors in the UK. Characterizing changes
      over time can help understanding the mechanisms that underpin health
      inequalities. These pathways are complex and operate at different levels, from
      the individual to the context where someone lives. In this commentary I highlight
      some of the issues and uncertainties that may arise when individual and area
      level measures are used indistinctively.

PMID- 22401666
TI  - Development of the spinal cord and peripheral nervous system in platypus
      (Ornithorhynchus anatinus) and short-beaked echidna (Tachyglossus aculeatus).
AB  - The modern monotremes (platypus and echidnas) are characterized by development of
      their young in a leathery egg that is laid into a nest or abdominal pouch. At
      hatching, the young are externally immature, with forelimbs capable of
      digitopalmar prehension, but hindlimbs little advanced beyond limb buds. The
      embryological collections at the Museum fur Naturkunde in Berlin were used to
      examine the development of the spinal cord and early peripheral nervous system in
      developing monotremes and to correlate this with known behavioural development.
      Ventral root outgrowth to the bases of both the fore- and hindlimbs occurs at 6.0
      mm crown-rump length (CRL), but invasion of both limbs does not happen until
      about 8.0-8.5 mm CRL. Differentiation of the ventral horn precedes the dorsal
      horn during incubation and separate medial and lateral motor columns can be
      distinguished before hatching. Rexed's laminae begin to appear in the dorsal horn
      in the first week after hatching, and gracile and cuneate fasciculi emerge during
      the first two post-hatching months. Qualitative and quantitative comparisons of
      the structure of the cervicothoracic junction spinal cord in the two monotremes
      with that in a diprotodont marsupial (the brush-tailed possum, Trichosurus
      vulpecula) of similar size at birth, did not reveal any significant structural
      differences between the monotremes and the marsupial. The precocious development
      of motor systems in the monotreme spinal cord is consistent with the behavioural
      requirements of the peri-hatching period, that is, rupture of embryonic membranes
      and egg, and digitopalmar prehension to grasp maternal hair or nest material.

PMID- 22401667
TI  - Advances in using PARP inhibitors to treat cancer.
AB  - The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a critical role
      in the maintenance of DNA integrity as part of the base excision pathway of DNA
      repair. PARP1 is overexpressed in a variety of cancers, and its expression has
      been associated with overall prognosis in cancer, especially breast cancer. A
      series of new therapeutic agents that are potent inhibitors of the PARP1 and
      PARP2 isoforms have demonstrated important clinical activity in patients with
      breast or ovarian cancers that are caused by mutations in either the BRCA1 or 2
      genes. Results from such studies may define a new therapeutic paradigm, wherein
      simultaneous loss of the capacity to repair DNA damage may have antitumor
      activity in itself, as well as enhance the antineoplastic potential of cytotoxic
      chemotherapeutic agents.

PMID- 22401668
TI  - Panchromatic photon-harvesting by hole-conducting materials in inorganic-organic
      heterojunction sensitized-solar cell through the formation of nanostructured
      electron channels.
AB  - Additional photon-harvesting by hole transporting materials in Sb(2)S(3)
      sensitized solar cell is demonstrated through the formation of electron channels
      in the hole transporter such as P3HT (poly(3-hexylthiophene)) and
      PCPDTBT(poly(2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)
      alt-4,7(2,1,3-benzothiadiazole)) that can act as both a hole conductor and light
      absorber. As a result, the short-circuit current density is improved with an
      increment in overall efficiency. These findings provide new insights into use of
      light-absorbing conjugated polymers as a hole conductor in the inorganic-organic
      heterojunction sensitized solar cells.

PMID- 22401669
TI  - Clinical and genetic characterization of a 2-year-old boy with complete PLP1
      deletion.
AB  - We report herein a case of 2-year-old boy diagnosed with a mild form of Pelizaeus
      Merzbacher disease due to deletion of the entire proteolipid protein 1 (PLP1)
      gene. The patient demonstrated spastic quadriplegia, mental retardation, and
      microcephaly. He exhibited brainstem auditory evoked potentials with prolonged
      interpeak latencies and magnetic resonance imaging characteristics suggestive of
      hypomyelination in most areas of the brain with the exception of the brainstem,
      cerebellar peduncles, corpus callosum, and the posterior limbs of the internal
      capsules. Proton magnetic resonance spectroscopy revealed a mildly reduced ratio
      of N-acetyl aspartate to creatine levels in the white matter, suggesting axonal
      involvement. Additionally, nerve conduction velocity of the lower extremities was
      mildly decreased. Genetic analysis showed a deletion of PLP1 in this patient.
      Further genome mapping followed by sequence analysis of the deletion breakpoints
      revealed that a genomic region, about 73 kb in length, including the entire PLP1
      and RAB9B, was deleted. The size of the deletion was the smallest among those
      previously reported in this region. Except for the 1-base pair microhomology,
      there were no homologous sequences between the regions around the distal and
      proximal breakpoints, which suggests that the deletion occurred by nonhomologous
      end joining.

PMID- 22401670
TI  - Abnormalities of joint mobility and gait in children with autism spectrum
      disorders.
AB  - AIMS: Abnormalities of gross motor function in children with autism are well
      known to clinicians but have not received much empirical documentation and, with
      the exception of stereotypies, are not among its diagnostic criteria. We recorded
      the characteristics of gait and prevalence of toe walking, the range of passive
      joint mobility, and age at walking in children with DSM IV autism spectrum
      disorders (ASDs) and in age- and gender-matched typically developing peers (mean
      age 4years 6months, range 22months-10years 9months). METHODS: We evaluated
      maximum range of mobility at the elbow, wrist, metacarpo-phalangeal, and ankle
      joints and videoed children walking and running. Two neurologists blind to
      diagnosis independently scored features of gait clinically. RESULTS: Children
      with ASDs had significantly greater joint mobility (p<.002), more gait
      abnormalities (p<.0001), and on average walked 1.6months later than their non
      autistic peers. INTERPRETATION: This study indicates that attention should be
      directed to motor abnormalities as well as sociability, communication, and
      restricted and repetitive behaviors in individuals with ASDs. Motor deficits add
      to children's other handicaps. They indicate that ASDs affect a broader range of
      central nervous system circuitry than often appreciated.

PMID- 22401671
TI  - Indium(III) chloride catalyzed conjugate addition reaction of alkynylsilanes to
      acrylate esters.
AB  - A novel and efficient procedure for the synthesis of delta,gamma-alkynyl esters
      by the conjugate addition of alkynylsilanes to acrylate esters in the presence of
      a catalytic amount of indium(III) chloride has been developed. This method
      provides a rapid and efficient access to substituted delta,gamma-alkynyl esters.

PMID- 22401672
TI  - Potent antiviral HIV-1 protease inhibitor GRL-02031 adapts to the structures of
      drug resistant mutants with its P1'-pyrrolidinone ring.
AB  - GRL-02031 (1) is an HIV-1 protease (PR) inhibitor containing a novel P1' (R)
      aminomethyl-2-pyrrolidinone group. Crystal structures at resolutions of 1.25-1.55
      A were analyzed for complexes of 1 with the PR containing major drug resistant
      mutations, PR(I47V), PR(L76V), PR(V82A), and PR(N88D). Mutations of I47V and V82A
      alter residues in the inhibitor-binding site, while L76V and N88D are distal
      mutations having no direct contact with the inhibitor. Substitution of a smaller
      amino acid in PR(I47V) and PR(L76V) and the altered charge of PR(N88D) are
      associated with significant local structural changes compared to the wild-type
      PR(WT), while substitution of alanine in PR(V82A) increases the size of the S1'
      subsite. The P1' pyrrolidinone group of 1 accommodates to these local changes by
      assuming two different conformations. Overall, the conformation and interactions
      of 1 with PR mutants resemble those of PR(WT) with similar inhibition constants
      in good agreement with the antiviral potency on multidrug resistant HIV-1.

PMID- 22401673
TI  - [Scratched faces: treatment of dynamic facial wrinkles through the simultaneous
      combined use of botulinium toxin A and hyaluronic acid].
AB  - We use the term "scratched face" to define a face which has been streaked by deep
      wrinkles stretching from the orbital frame up to the temples and neck. Although
      the origin of these wrinkles seems to be the mime muscle effect; it may also be
      linked to the presence of Acetylcholine skin receptors in the superficial skin.
      This would certainly explain the reason for the presence of these wrinkles far
      from the muscle areas. We can therefore offer very superficial and targeted
      injections of diluted botulinium Toxin A. In the case of a strongly dehydrated
      skin, the toxin will be combined in the same syringe with a weak or not
      reticulated hyaluronic acid. We present a case study of 25 patients who have
      received this treatment, with a follow-up from 3 to 18 months. These patients had
      not received until now a satisfactory answer to the problem of their particularly
      striking facial distortions.

PMID- 22401674
TI  - Results of 3,668 primary total hip replacements.

PMID- 22401675
TI  - Epidemiology of adult ankle fractures in Sweden between 1987 and 2004: a
      population-based study of 91,410 Swedish inpatients.
AB  - BACKGROUND AND PURPOSE: Previous national epidemiological data on the
      characteristics and trends of patients with ankle fractures have been limited. We
      therefore analyzed data on Swedish inpatients with ankle fractures in this
      nationwide population study, based on data from 1987 through 2004. PATIENTS AND
      METHODS: Data on all inpatients aged 15 years and older with ankle fracture were
      extracted from the Swedish National Patient Register for the period 1987-2004.
      RESULTS: We identified 91,410 hospital admissions with ankle fracture,
      corresponding to an annual incidence rate of 71 per 10(5) person-years. During
      the study period, the number of hospital admissions increased by 0.2% annually,
      mainly from increase in fracture incidence in the elderly women. Mean age at
      admission was 45 (SD 19) years for men and 58 (18) for women. The major mechanism
      of injury was falling at the same level (64%). INTERPRETATION: This nationwide
      study of inpatients with ankle fractures showed an increase in fracture
      incidence, particularly in elderly women.

PMID- 22401676
TI  - The Exeter femoral stem continues to migrate during its first decade after
      implantation: 10-12 years of follow-up with radiostereometric analysis (RSA).
AB  - BACKGROUND: Due to its collarless, double-tapered polished design, the Exeter
      femoral stem is known to migrate distally in the first 5 years after
      implantation. However, its long-term migration pattern has not been investigated.
      PATIENTS AND METHODS: 39 consecutive patients (41 total hip arthroplasties)
      received a cemented Exeter stem and had prospective clinical and RSA follow-up.
      Patients were evaluated postoperatively at 6, 12, 26, and 52 weeks, and annually
      thereafter. Short-term results have been reported. In this study, the mean length
      of follow-up was 9.4 years (SD 3.2 years). No patients were lost to follow-up. 15
      patients died during follow-up. RESULTS: No stems were revised. In 4 stems,
      fractures of the cement mantle were noted within the first 3 postoperative years.
      In 3 stems, this resulted in a complete circumferential cement mantle
      discontinuity. For the 37 well-performing stems, continuous but small migration
      was measured between 2 and 12 years of follow-up. Continued subsidence of 0.08
      mm/year (95% CI: 0.05-0.12, p < 0.001) was seen in combination with continued
      rotation in retroversion of 0.07 degrees /year (95% CI: 0.02-0.12, p = 0.01). At
      10 years of follow-up, mean subsidence was 2.1 (SD 1.2) mm and mean retroversion
      was 1.8 degrees  (SD 2.0). Two-thirds of this occurred during the first 2
      postoperative years. In the 3 stems with a complete circumferential cement
      fracture, a sudden and disproportionately high increase in subsidence was
      measured in the time period of occurrence. INTERPRETATION: The Exeter femoral
      stem continues to migrate during the first decade after implantation. Absolute
      stability is not required for good long-term survival if this is compatible with
      the design of the implant.

PMID- 22401677
TI  - Should deep venous thrombosis prophylaxis be used in fast-track hip and knee
      replacement?

PMID- 22401678
TI  - Is MRA an unnecessary expense in the management of a clinically unstable
      shoulder? A comparison of MRA and arthroscopic findings in 90 patients.
AB  - BACKGROUND AND PURPOSE: In detection of glenoid labrum pathology, MR arthrography
      (MRA) has shown sensitivities of 88-100% and specificities of 89-93%. However,
      our practice suggested that there may be a higher frequency of falsely negative
      reports. We assessed the accuracy of this costly modality in practice. PATIENTS
      AND METHODS: We retrospectively reviewed MRA reports of 90 consecutive patients
      with clinical shoulder instability who had undergone shoulder arthroscopy. All
      had a history of traumatic anterior shoulder dislocation and had positive
      anterior apprehension tests. All underwent arthroscopy and stabilization during
      the same procedure. We compared the findings, using arthroscopic findings as the
      gold standard in the identification of glenoid labrum pathology. RESULTS: 83 of
      the 90 patients had glenoid labrum tears at arthroscopy. Only 54 were correctly
      identified at MRA. All normal glenoid labra were identified at MRA. This gave a
      sensitivity of 65% and a specificity of 100% in identification of all types of
      glenoid labrum tear. 74 patients had anterior glenoid labral tears that were
      detected at an even lower rate of sensitivity (58%). INTERPRETATION: The
      sensitivity of MRA in this series was substantially lower than previously
      published, suggesting that MRA may not be as reliable a diagnostic imaging
      modality in glenohumeral instability as previously thought. Our findings
      highlight the importance of an accurate history and clinical examination in the
      management of glenohumeral instability. The need for MRA may not be as high as is
      currently believed.

PMID- 22401679
TI  - Factors predisposing to claims and compensations for patient injuries following
      total hip and knee arthroplasty.
AB  - BACKGROUND AND PURPOSE: Factors associated with malpractice claims are poorly
      understood. Knowledge of these factors could help to improve patient safety. We
      investigated whether patient characteristics and hospital volume affect claims
      and compensations following total hip arthroplasty (THA) and knee arthroplasty
      (TKA) in a no-fault scheme. METHODS: A retrospective registry-based study was
      done on 16,646 THAs and 17,535 TKAs performed in Finland from 1998 through 2003.
      First, the association between patient characteristics-e.g., age, sex,
      comorbidity, prosthesis type-and annual hospital volume with filing of a claim
      was analyzed by logistic regression. Then, multinomial logistic regression was
      applied to analyze the association between these same factors and receipt of
      compensation. RESULTS: For THA and TKA, patients over 65 years of age were less
      likely to file a claim than patients under 65 (OR = 0.57, 95% CI: 0.46-0.72 and
      OR = 0.65, CI: 0.53-0.80, respectively), while patients with increased
      comorbidity were more likely to file a claim (OR = 1.17, CI: 1.04-1.31 and OR =
      1.14, CI: 1.03-1.26, respectively). Following THA, male sex and cemented
      prosthesis reduced the odds of a claim (OR = 0.74, CI: 0.60-0.91 and OR = 0.77,
      CI: 0.60-0.99, respectively) and volume of between 200 and 300 operations
      increased the odds of a claim (OR = 1.29, CI: 1.01-1.64). Following TKA, a volume
      of over 300 operations reduced the probability of compensation for certain injury
      types (RRR = 0.24, CI: 0.08-0.72). INTERPRETATION: Centralization of TKA to
      hospitals with higher volume may reduce the rate of compensable patient injuries.
      Furthermore, more attention should be paid to equal opportunities for patients to
      file a claim and obtain compensation.

PMID- 22401680
TI  - [A hypothesis on the pathogeny of rounded and linear epidermal nevi (nevoid
      acanthosis nigricans)].

PMID- 22401681
TI  - [Chronically neglected malignant skin tumours].

PMID- 22401682
TI  - [Nevoid acanthosis nigricans or RAVEN (rounded and velvety epidermal nevus):
      three cases].
AB  - BACKGROUND: We report three cases of a peculiar rash with mixed clinical features
      of both epidermal nevus and acanthosis nigricans. Their characteristics have been
      compared to those of very rare but similar cases found in the medical literature.
      PATIENTS AND METHODS: Two young adults (one male, one female) and a 7-year-old
      boy consulted for hyperchromic asymptomatic plaques located respectively on the
      right scapula, the left upper arm and the right frontotemporal area of the face.
      None had any noticeable familial medical history. None were overweight or had a
      personal history of diabetes or endocrine dysfunction. The plaques had appeared
      soon after puberty in the adults and at the age of 4 years in the child and they
      had remained stable for years. They were polycyclic in shape, sharply demarcated,
      and with a linear distribution. Their surface was slightly papular, with a
      velvety appearance and texture. No other skin or mucous membrane lesions were
      observed elsewhere. The physical examination was otherwise normal. Skin biopsy
      specimens showed mild acanthosis with papillomatosis, hyperorthokeratosis with
      elongated rete ridges and slight thinning of the roof of the dermal papilla.
      DISCUSSION: The striking clinical features of this rash rule out confusion with
      any other epidermal nevus (because of age of onset, shape and texture) or with
      acanthosis nigricans (because of its topography and the lack of associated
      neoplastic or endocrine disease). A dozen similar case reports can be found in
      the medical literature, mostly under the term "nevoid acanthosis nigricans". Such
      a rash may be linked to postzygotic mosaicism with the same mutations of the
      FGFR3 gene. However, since the physiopathology of this rash remains hypothetical,
      we propose to name it "RAVEN", for "rounded and velvety epidermal nevus", which
      is simply a descriptive acronym and nothing more.

PMID- 22401683
TI  - [Historic malignant tumour: 27 observations].
AB  - BACKGROUND: When used in the French medical literature to describe a pathological
      state, the word "historic" normally refers to tumours of startling appearance
      because of their size. It is difficult to understand how a patient can allow such
      tumours to continue to grow. We attempt to define this concept. PATIENTS AND
      METHODS: Two dermatologists carried out a retrospective, independent and
      comparative selection of photographs taken between 1978 and 2008 of malignant
      cutaneous tumours of unusual size given the histological diagnosis. Socio
      professional, demographic, clinical, histological psychological data, and details
      of treatment history and progress were collected. RESULTS: Twenty-seven patients
      (11 M, 16 F) of mean age 74 years (34-99 years) presented a "historic" tumour.
      Twelve patients lived in rural regions. Five patients were company executives.
      The average duration of development of the "historic" tumours was 4.5 years (6
      420 months). The tumours were classed histologically as epidermoid carcinomas
      (nine) and melanomas (seven). The mean size was 13 cm (6-30 cm). Psychiatric
      problems, membership of sects or dementia were noted for 13 patients. Treatment
      consisted of chemotherapy, radiotherapy or, less frequently, surgery. Eighteen
      patients died on average 13 months after diagnosis. DISCUSSION: "Historic"
      malignant tumour (also described in the literature as "giant" tumour) is a real
      life fact. No studies have been made of a series of such patients. Despite
      histological diagnosis, the size was associated with slow tumoral progress and/or
      late treatment, chiefly accounted for by psychiatric disorders. Socio
      professional data indicate that "historic" tumours are equally common in urban
      and rural areas.

PMID- 22401684
TI  - [Neglected skin tumors. Three cases].
AB  - BACKGROUND: Giant skin tumours are defined as greater than 10 cm in size and are
      frequently a consequence of neglect. We report three cases of giant skin tumours
      and discuss possible factors associated with delayed diagnosis and treatment.
      OBSERVATIONS: Two men and one woman, aged 52, 62 and 78 years, presented with
      giant skin tumours. One was mentally retarded, one had a borderline personality
      and another was presenting a major depressive disorder. Pain, smell, bleeding
      and/or loss of function forced the patients to seek medical care. Tumour sizes
      were 11 to 30 cm and were present for between six months and 20 years. All
      patients had hidden their lesion from their doctor and families. In one case, a
      sebaceous carcinoma of the right shoulder required amputation of the right upper
      limb. In a second, palliative surgery and medical care was given for a metastatic
      porocarcinoma. The last patient received neoadjuvant chemotherapy for an
      undifferentiated carcinoma. DISCUSSION: Neglected skin tumours continue to be
      encountered even in 2011. Consultation was delayed due to fear of the diagnosis
      and/or lack of corresponding physicians, resulting in worsening of the prognosis.
      A larger scale study could help us to identify the factors associated with
      neglected giant tumours and to improve their management.

PMID- 22401685
TI  - [Skin necrosis during long-term fluindione treatment revealing protein C
      deficiency].
AB  - BACKGROUND: Cutaneous necrosis is a rare complication of vitamin K antagonist
      therapy. It presents as cutaneous hemorrhagic necrosis and usually occurs at the
      start of treatment. We describe an atypical case of recurrent skin necrosis after
      two years of treatment with fluindione. CASE REPORT: A 70-year old woman with a
      history of venous thromboembolism and obesity presented with a large haemorrhagic
      necrosis of the abdominal wall. She had been treated with fluindione for two
      years. Genetic protein C deficiency was discovered. Resumption of vitamin K
      antagonist therapy was followed by recurrence of skin necrosis despite
      concomitant administration of heparin. Treatment with vitamin K antagonists could
      not be continued. DISCUSSION: This observation is unusual due to the late onset
      of skin necrosis. The condition usually begins shortly after initiation of
      vitamin K antagonist therapy, generally between the third and the sixth day of
      treatment. It is due to a transient hypercoagulable state in patients with
      protein C deficiency or, in rare cases, protein S deficiency. This late-onset
      skin necrosis, occurring many years after initiation of anticoagulant therapy,
      may be explained by a sudden worsening of pre-existing protein C deficiency due
      to infectious and iatrogenic factors.

PMID- 22401686
TI  - [Subcutaneous infection spread by Scytalidium (Neoscytalidium) dimidiatum].
AB  - INTRODUCTION: S. dimidiatum (recently reclassified as N. dimidiatum) is a fungus
      that causes nail and/or superficial skin infection. It may also cause
      subcutaneous and deep infection, chiefly in immunocompromised patients. CASE
      REPORT: An 87-year-old male treated with oral corticosteroids for sarcoidosis
      consulted for violaceous cutaneous nodules on the back of his hands.
      Histopathological examination revealed epithelioid cell granulomas with numerous
      mycelial filaments and multiple spores. Culture of a biopsy sample resulted in
      growth of numerous colonies of S. dimidiatum and the patient was treated with
      intravenous amphotericin B. DISCUSSION: This organism is transmitted by direct or
      indirect contact with contaminated soil or plants. It mainly causes superficial
      skin and nail infections, and may result in deeper infections on rare occasions.
      We report a case of subcutaneous infection with S. dimidiatum in an
      immunocompromised patient (due to general steroid therapy) that was successfully
      treated using amphotericin B.

PMID- 22401687
TI  - [Atypical eruptive collagenoma: two cases].
AB  - BACKGROUND: Eruptive collagenoma is a rare cutaneous lesion seen in young adults.
      It consists of asymptomatic, flesh-coloured papules that are usually localised on
      the trunk and the root of the upper limbs. Herein we report two cases on account
      of the atypical topography of the lesions and the advanced age of the patients.
      CASE REPORTS: Case n 1: a 69-year-old man consulted for firm, whitish papules on
      the wrists, elbows, popliteal fossae and groin without associated signs, and
      which first appeared several years earlier. The standard laboratory assessment
      and ocular fundus test were normal. Case no 2: a 69-year-old woman had very firm,
      flesh-coloured papules on the trunk and the root of the limbs, which appeared
      after the age of 40. The results of ocular fundus, cardiovascular investigation
      and laboratory examinations were normal. The histology of papules was similar in
      both cases and revealed a nodular zone in the reticular dermis, comprising
      disorganized collagen bundles and excessive quantities of elastic fibres, without
      elastorrhexis. This histology was consistent with collagenoma. DISCUSSION: We
      report two singular cases that were atypical in terms of patient age and
      localisation in the flexion folds. Histological analysis of a papule enables a
      diagnosis of collagenoma to be made. Such analysis usually reveals a hamartoma in
      which the amount of collagen is increased, with variable quantities of elastic
      tissue, though often decreased. The principal differential diagnoses are elastoma
      and pseudoxanthoma elasticum.

PMID- 22401688
TI  - [Morel-Lavallee syndrome of the lower leg].
AB  - BACKGROUND: Morel-Lavallee syndrome, which appears after tangential trauma of
      highly vascularised tissues, is characterized by closed internal degloving
      injuries resulting in subcutaneous fluid collection. It can cause many
      complications. A 42-year-old man presented with open wounds after a violent right
      lower extremity trauma; the wounds were sutured. One month after the trauma, the
      patient complained of painful edema of the lower limb and fluid discharge from
      the previously sutured wounds. Local examination showed fluctuating fluid
      collection. Serum inflammatory markers were within the normal range. Ultrasound
      investigation of the right lower limb confirmed an extended fluid collection from
      the lower third of the thigh to the upper third of the leg, and CT scan
      delineated a surrounding capsule. The clinical and radiological data supported a
      diagnosis of post-traumatic Morel-Lavallee syndrome. Local surgical debridement
      and drainage associated with systemic antibiotic therapy (the fluid was found to
      be infected with oxacillin-resistant Staphylococcus epidermidis) resulted in
      rapid improvement. DISCUSSION: Morel-Lavallee syndrome commonly appear after
      tangential trauma of highly vascularised tissues. The skin and the subcutaneous
      fat tissue are abruptly torn from the underlying muscle fascia, shearing the
      lymphatic vessels, rendering lymphostasis impossible. The local inflammatory
      reaction can cause the formation of a fibrous capsule resulting in a fluid
      collection. The clinical signs are not specific. When examining a soft-tissue
      collection or slow-healing wounds, the dermatologist should always rule out
      previous soft-tissue trauma; simple imaging studies will confirm the diagnosis if
      Morel-Lavallee injuries are suspected. CONCLUSION: All dermatologists consulted
      by young patients without vascular disease for an unusual swelling and/or for
      slow-healing wounds should be mindful of this syndrome.

PMID- 22401689
TI  - [Capecitabine-induced hyperpigmentation followed by hand-foot syndrome: a new
      case report].

PMID- 22401690
TI  - [The impact of rosacea on patients' daily life: a transverse observational study
      among private dermatologists].

PMID- 22401691
TI  - [Recurrence of pustular erosive dermatosis of the leg after a skin graft].

PMID- 22401692
TI  - [Erosive and budding molluscum contagiosum: total regression under antiretroviral
      therapy].

PMID- 22401693
TI  - [Do palmar and plantar lesions occur during chickenpox?].

PMID- 22401694
TI  - [Dermatoses associated with high technology (cell phones, computers and video
      games)].

PMID- 22401695
TI  - [Syphilitic balanitis of Follmann].

PMID- 22401696
TI  - [Melanocytic tumours and genetics: new findings].

PMID- 22401697
TI  - [Combined skin infection after CO2 laser treatment].

PMID- 22401698
TI  - [Spontaneous keloid on the breast].

PMID- 22401699
TI  - [Nicorandil and ulceration: a physiopathological hypothesis].

PMID- 22401700
TI  - Women, but not men, report increasingly more pain during repeated (un)predictable
      painful electrocutaneous stimulation: Evidence for mediation by fear of pain.
AB  - An abundance of animal research suggests that fear inhibits pain whereas anxiety
      increases it. Human studies on this topic are more scarce, and the existing
      evidence seems rather inconsistent. Therefore, we aimed to investigate the
      divergent effects of both negative emotional states-that is, pain-related fear
      and anxiety on pain sensitivity and unpleasantness. Possible sex-related
      differences were also under investigation, as well as the potential mediational
      role of fear of movement-related pain on the differences in pain intensity and
      unpleasantness between both sexes. We employed a voluntary joystick movement
      paradigm using movements as conditioned stimuli (CSs) and a painful
      electrocutaneous stimulus as the unconditioned stimulus. Healthy participants
      received predictable shocks in one condition and unpredictable shocks in another
      condition. The former procedure is known to induce fear of movement-related pain
      to the CS+ movement (movement consistently followed by pain), whereas the latter
      procedure induces (contextual) pain-related anxiety. Results showed that fear of
      movement-related pain indeed resulted in decreased pain intensity/unpleasantness
      ratings, while pain-related anxiety led to increased pain
      intensity/unpleasantness reports. Further, the anticipated sex difference was
      modulated by time. That is, women gradually reported more pain/unpleasantness,
      whereas men do not show such a sensitization effect. Moreover, this sex-specific
      sensitization is partially mediated by (conditioned) fear of movement-related
      pain. Women also report increasingly more fear of pain over conditioning blocks,
      while men do not. These results might be interesting in the light of the
      overrepresentation of women in a number of clinical pain conditions as well as
      anxiety disorders.

PMID- 22401701
TI  - Neuropsychology and complex regional pain syndrome.

PMID- 22401702
TI  - A low proportion of HBeAg among HBsAg-positive pregnant women with known HIV
      status could suggest low perinatal transmission of HBV in Cameroon.
AB  - BACKGROUND: Transmission of hepatitis B virus (HBV) from HBV-positive mothers to
      their infants is common and usually occurs when the mother is hepatitis B e
      antigen (HBeAg) positive and/or has a high HBV DNA load. In this study, we
      determined the prevalence of hepatitis B surface antigen (HBsAg) and HBeAg among
      pregnant women with known HIV status. FINDINGS: A total of 650 pregnant women
      with a mean age of 26.2 years including 301 HIV-positives and 349 HIV-negatives
      were screened for HBsAg (Monolisa AgHBs Plus Biorad, France). Among the HBsAg
      positives, HBeAg and anti-HBe were tested (Monolisa Ag HBe Plus Biorad, France).
      Overall, 51 (7.85%) were positive for HBsAg. The prevalence of HBsAg was not
      statistically different between HIV-positive and HIV-negative pregnant women
      [28/301 (9.3%) vs 23/349 (6.59%); p = 0.2]. None of the 45 HBsAg-positive samples
      was reactive for HBeAg. CONCLUSIONS: Our study indicates a high prevalence of
      HBsAg with very low proportion of HBeAg in Cameroonian pregnant women. Since
      perinatal transmission of HBV is mostly effective when the mother is also HBeAg
      positive, our data could suggest that perinatal transmissions play a minor role
      in HBV prevalence in Cameroon. In line with previous African studies, these
      findings further suggests that horizontal transmission could be the most common
      mechanism of HBV infections in Cameroon.

PMID- 22401703
TI  - Acute toxicity study of liposomal antioxidant formulations containing N
      acetylcysteine, alpha-tocopherol, and gamma-tocopherol in rats.
AB  - Liposomes have been used for the delivery of antioxidants to different tissues
      and organs for the treatment of oxidative stress-induced injuries. In this study,
      the acute toxicity of a single dose of intravenously (i.v.) administered
      liposomal antioxidant formulation, containing N-acetylcysteine (NAC) with or
      without alpha-tocopherol (alpha-T) or gamma-tocopherol (gamma-T), in rats was
      examined. Each group consisted of 5 male and 5 female Sprague-Dawley rats, with a
      control group receiving empty dipalmitoylphosphatidylcholine (DPPC) liposomes
      (660 mg/kg) and test groups receiving DPPC liposomes (660 mg/kg) entrapped with
      1) NAC (200 mg/kg), 2) NAC (200 mg/kg) and alpha-T (83.3 mg/kg), and 3) NAC (200
      mg/kg) and gamma-T (71.4 mg/kg). These dose levels were determined from the dose
      range-finding study and were considered to be the maximum feasible dose (MFD)
      levels, based on the volume of 10 mL/kg and physical properties and viscosity of
      the test articles that could be safely administered to rats by an i.v. injection.
      Two weeks after treatment (day 15), rats in the control group and three test
      groups exhibited no clinical signs of toxicity during the dosing period or during
      the 14-day post-treatment period. Weight gain and food consumption in all animals
      was appropriate for the age and sex of animals. Clinical pathology findings
      (e.g., hematology, coagulation, clinical chemistry, and urinalysis) were
      unremarkable in all rats and in all groups. In conclusion, the results of this
      study showed no treatment-related toxicity in rats at the MFD level by a single
      bolus i.v. administration.

PMID- 22401704
TI  - Are sleep and life quality of family caregivers affected as much as those of
      hemodialysis patients?
AB  - OBJECTIVE: The purpose of this study was to determine and compare the quality of
      sleep, quality of life, and anxiety and depression symptoms reported by
      hemodialysis (HD) patients and family caregivers of HD patients. METHODS: The
      study included 142 pairs of HD patients and their caregivers. To assess quality
      of sleep, quality of life, and anxiety and depressive symptoms, the 36-item Short
      Form, Pittsburgh Sleep Quality Index (PSQI), and Hospital Anxiety and Depression
      Scale, respectively, were used. RESULTS: For the patients, 73.9% were poor
      sleepers. Low Physical Component Summary (PCS) and Mental Component Summary (MCS)
      scores were found in 89.1% and 76.3% of HD patients, respectively. For the
      caregivers, 88% were poor sleepers. Low PCS and MCS scores were found in 62% and
      70.4% of the caregivers, respectively. Mean PSQI scores, subjective sleep quality
      scores, sleep latency, sleep efficiency, sleep disturbance, use of sleep
      medications, and daytime dysfunction scores of the caregivers were significantly
      higher than the scores of the HD patients (P<.001). CONCLUSIONS: Caregivers of
      dialysis patients experience adverse effects on their quality of sleep and
      quality of life. Educational, social, and psychological support interventions
      should be considered to improve their ability to cope.

PMID- 22401705
TI  - The relationship between depressive symptoms and medication nonadherence in type
      2 diabetes: the role of social support.
AB  - OBJECTIVE: Medication adherence promotion interventions are needed that target
      modifiable behavioral factors contributing to the link between depressive
      symptoms and poor adherence to diabetes self-care behaviors. In an effort to
      identify what factors contribute to this link, we examined the role of social
      support as a mediator of the relationship between depressive symptoms and
      medication nonadherence. METHOD: We recruited 139 subjects with type 2 diabetes.
      Using an indirect effect test with bias-corrected (BC) bootstrapping, we tested
      whether depressive symptoms had an indirect effect on medication nonadherence
      through a lack of social support. RESULTS: More depressive symptoms were
      associated with medication nonadherence (total effect=.06, P<.001), more
      depressive symptoms were associated with less social support (direct effect of
      the predictor on the mediator=-.96, P=.02), and less social support was
      associated with medication nonadherence (direct effect of the mediator on the
      outcome=-.01, P<.01). While the relationship between more depressive symptoms and
      medication nonadherence persisted with social support in the predicted pathway,
      the degree of this relationship was partially explained by a relationship between
      more depressive symptoms and less social support (indirect effect=.01, 95% BC
      bootstrapped confidence interval of .0005 to .0325). CONCLUSION: Providing social
      support to patients with diabetes who have symptoms of depression may ameliorate
      some of the deleterious effects of depressive symptoms on medication
      nonadherence, but social support alone is not enough.

PMID- 22401706
TI  - Circulating cytokine concentrations are not associated with major depressive
      disorder in a community-based cohort.
AB  - OBJECTIVE: The objective was to test the hypotheses that cytokine levels are
      elevated in community-residing persons at high risk for obstructive sleep apnea
      with major depressive disorder (MDD) compared to nondepressive persons and that
      cytokine levels show stronger correlations with somatic than psychological
      symptoms of depression. METHOD: A case-control study within the cross-sectional
      Akershus Sleep Apnea Project was performed. Two controls matched for age, gender,
      metabolic syndrome and obstructive sleep apnea were drawn for each case of MDD.
      RESULTS: Group comparisons revealed no significant difference in the levels of 17
      cytokines [interleukin-1beta, -2,-4, -5, -6, -7, -8, -10, -12(p70), -13 and -17;
      tumor necrosis factor-alpha; interferon-gamma; granulocyte colony-stimulating
      factor; granulocyte-monocyte colony-stimulating factor; macrophage
      chemoattractant protein-1 and monocyte inhibitory protein-1beta] between persons
      with (n=34) and without MDD (n=68). There was no association between cytokines
      levels and MDD in multivariate regression analyses. The concentration of
      interleukin-4 was significantly more positively correlated with psychological
      than somatic symptoms (r=0.046 vs. -0.143, respectively, P=0.024), while no
      different correlations were observed for other cytokines. CONCLUSION: The
      cytokine levels were not elevated in MDD, and cytokine levels were not more
      strongly associated with somatic than psychological symptoms of depression. The
      depression-specific effect on inflammation may be weak in community-based samples
      with prevalent somatic comorbidity.

PMID- 22401707
TI  - Depression and heart disease in US adults.
AB  - OBJECTIVE: Major depressive disorder (MDD) with atypical features is
      characterized by mood reactivity, increased appetite/weight gain and hypersomnia.
      Since these characteristics may be associated with obesity and diabetes, we
      examined whether individuals with MDD with atypical features (MDD-AD) are more
      likely to exhibit cardiovascular disease than those with MDD without atypical
      features (MDD-NAD). METHODS: Participants in the National Epidemiologic Survey on
      Alcohol and Related Conditions, a nationally representative sample of
      noninstitutionalized US adults, were categorized as having no lifetime depression
      diagnosis (n=34,979), MDD-NAD (n=4632) and MDD-AD (n=1063) and reported physician
      confirmed specific cardiovascular diagnoses in the previous year. RESULTS:
      Compared to individuals without depression, those with MDD had a 50% increased
      odds of any cardiovascular diagnosis (P<.0001) independent of sociodemographic
      factors. Adjusting for sociodemographic differences in MDD subgroups, MDD-AD
      (compared to MDD-NAD) was associated with 60% (P<.0001) and 43% (P<.005)
      increases in the odds of hypertension and any cardiovascular diagnosis,
      respectively. These latter associations were no longer significant after
      adjusting for body mass index and substance use. CONCLUSION: Individuals with
      major depression are at increased risk of heart disease. Whereas major depression
      with atypical features is associated with certain cardiovascular risk factors,
      there is no greater risk of cardiovascular diagnoses.

PMID- 22401709
TI  - Structures, binding energies, and spin-spin coupling constants of geometric
      isomers of pnicogen homodimers (PHFX)2, X = F, Cl, CN, CH3, NC.
AB  - Ab initio MP2/aug'-cc-pVTZ calculations have been carried out to determine the
      structures and binding energies of homodimers (PHFX)(2) for X = F, Cl, CN, CH(3),
      and NC. Geometric isomers of these complexes with C(i) symmetry exist, which are
      differentiated in terms of the nature of the atoms (F-P...P-F, H-P...P-H, or A
      P...P-A, with A being the atom of X directly bonded to P), which approach a
      nearly linear alignment. Of these, isomers having F-P...P-F linear are the most
      stable. Binding energies, intermolecular distances, and EOM-CCSD spin-spin
      coupling constants are sensitive to both the nature of X and the atoms that
      assume the linear alignment.

PMID- 22401710
TI  - Preparation and in vitro/in vivo evaluation of a ketoprofen orally
      disintegrating/sustained release tablet.
AB  - CONTEXT: Orally disintegrating tablets (ODTs) with sustained release profiles are
      a new generation of ODTs called orally disintegrating/sustained release tablets
      (ODSRTs), which are convenient in use and able to slowly release drugs to
      maintain effective blood concentrations over a prolonged period of time.
      Ketoprofen, one of non-steroidal anti-inflammatory drugs, is an ideal model drug
      for ODSRTs. METHODS: We designed a simple two-step process to develop novel
      ketoprofen orally disintegrating/sustained release tablets (KODSRTs). Firstly,
      sustained release ketoprofen fine granules were developed by spray drying the
      aqueous dispersions composed of Eudragit RS-30D, Starch 1500 and PEG 6000. The
      optimal parameters of spray drying were 100 degrees C for inlet air temperature
      and 1.5 mL/min for feed rate. Subsequently, the obtained granules were directly
      compressed into KODSRTs after mixing with lactose, mannitol and a
      superdisintegrant, crosslinked polyvinylpyrrolidone (PVPP). The characteristics
      of KODSRTs, especially their potential for extended drug release, were evaluated.
      RESULTS: Results of an in vitro release test demonstrated that KODSRTs could
      slowly release ketoprofen for 24 h after disintegrating within 30 s. Extended
      release properties of KODSRTs were decided by the ketoprofen sustained release
      fine granules in tablets. Besides, the disintegration time of KODSRTs depended on
      the percentage of PVPP in tablets. In vivo pharmacokinetic studies in beagles
      also showed that KODSRTs possessed a significantly extended release profile
      compared with ketoprofen normal capsules. CONCLUSION: KODSRTs were successfully
      prepared using a simple two-step process: spray drying and direct compression.

PMID- 22401711
TI  - Enhanced glucosamine production by Aspergillus sp. BCRC 31742 based on the time
      variant kinetics analysis of dissolved oxygen level.
AB  - This work aims to enhance the glucosamine production by Aspergillus sp. BCRC
      31742 via the optimization of dissolved oxygen (DO) control strategy. Influence
      of DO levels (20, 30, 40, 50 and 60%) on the glucosamine production was
      investigated, and it was found that the highest specific glucosamine production
      rate during 0-12h and 12-60 h was obtained at DO level of 30% and 50%,
      respectively. Accordingly, a two-stage DO control strategy was proposed, namely,
      DO was controlled at 30% during 0-12h and 50% during 12-60 h. With this DO
      shifting strategy, the highest glucosamine production reached 14.37 g/L, which
      was 1.30 times that without DO control. Here, the developed two-stage DO control
      strategy may be useful for the industrial production of glucosamine, and also may
      be meaningful for the production of other fine chemicals by the filamentous fungi
      fermentation.

PMID- 22401712
TI  - Biodiesel production from algae oil high in free fatty acids by two-step
      catalytic conversion.
AB  - The effect of storage temperature and time on lipid composition of Scenedesmus
      sp. was studied. When stored at 4 degrees C or higher, the free fatty acid
      content in the wet biomass increased from a trace to 62.0% by day 4. Using two
      step catalytic conversion, algae oil with a high free fatty acid content was
      converted to biodiesel by pre-esterification and transesterification. The
      conversion rate of triacylglycerols reached 100% under the methanol to oil molar
      ratio of 12:1 during catalysis with 2% potassium hydroxide at 65 degrees C for 30
      min. This process was scaled up to produce biodiesel from Scenedesmus sp. and
      Nannochloropsis sp. oil. The crude biodiesel was purified using bleaching earth.
      Except for moisture content, the biodiesel conformed to Chinese National
      Standards.

PMID- 22401713
TI  - Triflate-catalyzed (trans)esterification of lipids within carbonized algal
      biomass.
AB  - This study demonstrates the utility of rare-earth metal triflate catalysts (i.e.,
      Sc(OTf)(3) and In(OTf)(3)) in the (trans)esterification of oleic acid as well as
      the lipids contained within carbonized algal biomass using ethanol in the
      presence of water. Both catalysts are highly active between 200 and 235 degrees C
      with an ethanol:fatty acid (EtOH:FA) molar ratio of 10-20:1 and showed a high
      tolerance for moisture. Lipids within hydrochars produced by reacting Chlorella
      protothecoides paste (25% solids) in high temperature water (220-250 degrees C)
      were successfully converted into fatty acid ethyl esters (FAEE). The highest FAEE
      yields (85-98%) were obtained when hydrochars were reacted for 60 min at 215
      degrees C with about 11-13 mol% Sc(OTf)(3), a 17-19:1 EtOH:FA molar ratio, and
      without water. FAEE yields remained as high as 93% in the presence of 9 wt.%
      water. Our preliminary results warrant further work to optimize triflate
      catalyzed in situ (trans)esterification at low catalyst and ethanol loadings.

PMID- 22401714
TI  - Enhanced production of thrombinase by Streptomyces venezuelae: kinetic studies on
      growth and enzyme production of mutant strain.
AB  - This investigation provides the enhanced production of thrombinase, a
      fibrinolytic enzyme using mutant Streptomyces venezuelae. Initially the
      mutagenesis of the marine isolate was done by UV and Ethyl methane sulfonate
      (EMS) and their mutational efficiencies were compared. The mutants were selected
      based on their high thrombinase activity and used for further studies. The mutant
      was found to be more halo and thermo tolerant comparing to wild. The effect of
      Dissolved oxygen level was also determined and the mutant offered the maximum
      specific growth rate as 0.2404 (h(-1)). The mutant showed high resistance to
      higher initial lactose concentration and the inhibition concentration was found
      to be 155.1mg/mL. The effect of S(0)/X(0) ratio on specific substrate consumption
      and production rate were also investigated. Both mutant and wild showed increase
      in specific substrate consumption and production rate at higher S(0)/X(0) ratio
      but the mutant showed better values than the wild strain.

PMID- 22401715
TI  - Dynamic behavior and concentration distribution of granular sludge in a super
      high-rate spiral anaerobic bioreactor.
AB  - Dynamic behavior and concentration distribution of granular sludge is highly
      dependent on the ecological environment of microbial communities and substrate
      degradation efficiency along bed height. Both were modeled and verified through
      experiments in a super-high-rate spiral anaerobic bioreactor (SSAB). The sludge
      transport efficiency of upmoving biogas (k(t),(n)(-1)) displaying dynamic
      behavior of granular sludge in SSAB were predicted and found to be much lesser
      than of upflow anaerobic sludge blanket (UASB). The bed concentration
      distribution (C(m),(n)(-1)/C(m),(n)) which represented concentration distribution
      of granular sludge were also quantitatively predicted in two feeding strategies.
      Parametric sensitivity suggested that k(t),(n)(-1) was significantly influenced
      by spiral angle, outer radii of spiral rectangular channel, settling velocity of
      granular sludge and superficial liquid velocity (v(l)), while C(m),(n)(
      1)/C(m),(n) was affected by v(l) and superficial biogas velocity. In addition,
      some measures were also suggested to optimize designs and operations of such
      bioreactors.

PMID- 22401716
TI  - Hydroxide ion versus chloride and methoxide as an exogenous ligand reveals the
      influence of hydrogen bonding with second-sphere coordination water molecules in
      the electron transfer kinetics of Mn complexes.
AB  - We recently reported on the synthesis of a new pentadentate N(4)O ligand, tBuL(
      ), together with the X-ray diffraction structure of the corresponding mononuclear
      manganese(III)-hydroxo complex namely [(tBuL)Mn(III)OH](ClO(4)), (1 (ClO(4))).
      [El Ghachtouli et al. Energy Environ. Sci. 2011, 4, 2041.] In the present work,
      we evidence through electrochemical analysis that complex 1(+), in the presence
      of water, shows a peculiar behavior toward electron-transfer kinetics. The
      synthesis, single-crystal X-ray diffraction, and EPR spectroscopic
      characterization of two other mononuclear manganese(III)-chlorido and methoxo
      complexes-namely, [(tBuL)Mn(III)Cl](PF(6)), (2(PF(6))) and
      [(tBuL)Mn(III)OMe](ClO(4)), (3(ClO(4)))-are also reported. 2(PF(6)) and 3(ClO(4))
      compounds will serve as reference complexes for the electron-transfer kinetics
      investigation. The peculiar behavior of 1(ClO(4)) is attributed to the
      specificity of hydroxide anion as ligand presumably allowing intermolecular
      hydrogen-bonding interactions and thus affecting electron-transfer properties.

PMID- 22401717
TI  - Analysis of the association of an MMP1 promoter polymorphism and transcript
      levels with chronic periodontitis and end-stage renal disease in a Brazilian
      population.
AB  - Chronic periodontitis (CP) and end-stage renal disease (ESRD) are complex
      inflammatory conditions. Higher levels of MMP-1 were found in fluids and gingival
      tissues from CP patients and in the blood and tissues from ESRD patients. MMP1
      1607 (1G/2G) is a functional polymorphism, as it alters MMP-1 expression.
      OBJECTIVE: The aim of this study was to investigate the association of the MMP1
      1607 (1G/2G) polymorphism with CP and ESRD and evaluate differences in transcript
      levels between the groups. DESIGN: A total of 254 individuals were divided into
      four groups: Group 1, without CP and without chronic kidney disease (CKD) (n =
      67); Group 2, with CP and without CKD (n = 60); Group 3, without CP and with CKD
      stage 5 (ESRD) (n = 52), and Group 4, with CP and with ESRD (n = 75). The MMP1
      1607 polymorphism was analysed by PCR-RFLP. MMP1 gene transcripts from gingival
      tissues were analysed by real-time PCR. RESULTS: No association was found between
      the MMP1-1607 polymorphism and CP or ESRD. Increased levels of MMP1 transcripts
      were observed in CP patients with or without ESRD. No differences were observed
      in the transcript levels according to the genotypes. CONCLUSION: It was concluded
      that the MMP1-1607 polymorphism was not associated with either CP or ESRD.
      However, higher levels of MMP1 gene transcripts were found at gingival sites of
      CP in patients both with and without ESRD.

PMID- 22401718
TI  - [Inflammation, smoking and chronic obstructive pulmonary disease. Too many
      questions, few responses].

PMID- 22401719
TI  - [Economic evaluation of HemoCue(r) as a fast method to measure hemoglobin in
      outpatients].

PMID- 22401720
TI  - [Hepatitis B virus resistance to entecavir].

PMID- 22401721
TI  - [Changes in the European normative of clinical trials (i): a chance to improve
      the paperwork authorization].

PMID- 22401722
TI  - [Usefulness of Clinical Genetics in medical practice].

PMID- 22401723
TI  - [Cushing syndrome with clinical response to beta-blockers].

PMID- 22401724
TI  - [Diagnostic criteria for hypoalphalipoproteinemia and the threshold associated
      with cardiovascular protection in a Mexican Mestizo population].
AB  - BACKGROUND AND OBJECTIVES: In the Mexican Mestizo and Indian populations it is
      unknown the diagnostic criteria (DC) and associated risk of myocardial infarction
      (MI) for the HDL-cholesterol (HDL-c). We aimed to establish, in a Mexican adult
      population without cardiovascular risk factors, their HDL-c concentrations, the
      DC for hypoalphalipoproteinemia and prevalence base on the percentile-10 and the
      risk associated with MI, as well as the threshold (TH) associated with
      cardiovascular protection. SUBJECTS AND METHODS: In 826 adult Mestizos, 98
      Indians and 155 Mestizos with MI for the first time the average HDL-c serum
      concentrations were determined. Then the percentile and statistical analysis were
      carried out. RESULTS: The average HDL-c (mg/dl) concentrations for Mestizos and
      Indians were 43.2 and 37.2 and the ones inferior to the percentile-10 were <30
      and <26, respectively. In Mestizos, HDL-c concentrations of <= 35 mg/dl (odds
      ratio [OR] 1.91, 95% confidence interval [95%CI] 1.3-2.8, P=.001) were associated
      with MI and those >35 (OR 0.52, IC 95% 0.36-0.76, P=.001) were associated with a
      cardiovascular protection of 52%. The hypoalphalipoproteinemia prevalences in
      Mestizos and Indians were: for the percentile-10 DC 9 and 11% and for the TH
      associated with MI <= 35, 26 and 54%, respectively. CONCLUSIONS: The Indians
      average HDL-c concentration was significantly lower (P<.003) than for Mestizos.
      The established DC showed that the hypoalphalipoproteinemia prevalences in both
      populations were similar to those for other open populations. In Mestizos, HDL-c
      concentrations > 35 mg/dl are protective for MI, but it will be necessary to
      establish this TH for the Indian population. Each population should establish its
      own DC for hypoalphalipoproteinemia.

PMID- 22401726
TI  - [Preventing the risk of postpartum depression and premature childbirth by a
      psychosomatic approach: a randomized multicenter study].
AB  - BACKGROUND AND OBJECTIVE: Randomized studies to assess postnatal depression and
      preterm childbirth are rarely in conjunction; the 2 problems are treated
      separately regardless of their common risk factors. The main objective of this
      study was to evaluate the effects of a prenatal program based on a psychosomatic
      approach on the risk of postpartum depression (PPD) and preterm childbirth.
      SUBJECTS AND METHOD: Controlled clinical trial, randomized and multicenter study.
      A total of 184 pregnant women identified as vulnerable to PPD who had
      psychosocial risk factors associated with preterm childbirth were assigned to the
      experimental group (EG) (n=92) or control group (CG) (n=92), according to a
      computerized program. The EG participated in the program with a psychosomatic
      approach (10 sessions (one/week) for 2 h, 15 m) with a phone call between
      sessions; the objectives implicated the mother, father and baby contemplating
      pregnancy, childbirth and postpartum. Women in the EC made the usual program of
      the health center (8-10 weekly sessions of 2 hours), with no calls, with targets
      aimed at delivery. There were 2 evaluations: one in pregnancy and another in
      postpartum (T(1) and T(2)) including symptoms of depression (EPDS), social
      support (FSSQ), stress (scale events), the relationship (DAS) and the preterm
      childbirth. RESULTS: There was a difference of 11.2 in the percentage of cases at
      risk of PPD (EPDS>=12): 45.5% (27) in the CG and 34.3% (24) in the EG, without
      reaching statistical significance (P=.26). The preterm delivery showed
      significance differences (P=.003), with a decrease in preterm childbirth 4 times
      lower in the EG. CONCLUSIONS: Overall, the percentage of mothers at PPD risk was
      higher (P=.02) in women with preterm childbirth. It would be appropriate a global
      obstetrics and psychiatry approach.

PMID- 22401725
TI  - [Tumor necrosis factor as an early marker of inflammation in healthy smokers].
AB  - BACKGROUND AND OBJECTIVES: Smoking creates an inflammation that leads to lose of
      lung function. Tumor necrosis factor alpha (TNF-alpha) is a cytokine that plays
      an important role in the pathogenesis of chronic obstructive pulmonary disease.
      There is a need to develop methods for an early detection of an impaired lung
      function in smokers. We aimed to show that smokers have higher levels of TNF
      alpha in serum and exhaled breath condensate (EBC). We also analysed the
      influence of sex, age and weight on TNF-alpha, and determined the association
      between smoking, pulmonary function and TNF-alpha. PATIENTS AND METHODS:
      Prospective study of smokers and non-smokers without any known disease.
      Respiratory function tests, EBC and blood samples were performed before smoking
      cessation. STATISTICAL ANALYSIS: SPSS 11.0. RESULTS: Fifty-one patients (60.8%
      smokers), 56.9% females, mean age 39.88 years old. Smokers initiated at an age of
      15.77 years; the mean of cigarettes/day was 21.68. Significant differences in TNF
      alpha serum levels between smokers and non-smokers were observed (P<.043).
      Differences did not reach significance for EBC. For tobacco consumption data,
      only age at smoking initiation and serum TNF-alpha levels had a correlation. A
      significant relation between TNF-alpha serum levels and forced expiratory volume
      in one second and forced vital capacity was found. CONCLUSIONS: Smokers show
      higher TNF-alpha levels in serum. Number of years of smoking has an influence on
      TNF-alpha levels. There is a modest correlation between pulmonary function and
      plasma TNF-alpha levels, but not for EBC.

PMID- 22401727
TI  - [Optical neuritis in systemic lupus erythematosus].

PMID- 22401728
TI  - [The challenge of neuropathic pain].

PMID- 22401729
TI  - [Estimate of the 10-year risk of osteoporotic fractures in the Spanish
      population].
AB  - BACKGROUND AND OBJECTIVE: The QFRACTURE((r)) tool allows to estimate the risk of
      osteoporotic fractures in 10 years. We have estimated it, both for major and hip
      fracture, from the data obtained from the National Health Questionnaire. We thus
      estimated the risk of fragility fractures in the next 10 years in the Spanish
      population of both genders and calculated its burden. SUBJECTS AND METHODS: We
      have used the QFRACTURE((r)) tool which estimates the risk of any fracture and
      hip fracture in the next 10 years. RESULTS: A total of 552.879 women and 161.922
      men will suffer a fragility fracture in the next 10 years in Spain. Most of the
      fractures will happen in people aged 70 years old and more. In 10 years there
      will be 263.351 hip fractures in women and 84.213 in men. More than half of the
      hip fractures in women will happen to those aged more than 77 years old. The
      burden of osteoporotic fractures in Spain could arise to 4.778 millions of euros
      in the next 10 years with a cut-off of 3% for hip fracture accepting as reference
      the cost of generic alendronate. CONCLUSIONS: We have a first approach to the
      number of osteoporotic fractures in the next 10 years and its burden. The
      knowledge of this figures may be useful in order to program strategies to reduce
      the number of osteoporotic fractures in the future.

PMID- 22401730
TI  - [Diarrhea and abdominal enlargement in a young patient].

PMID- 22401731
TI  - [Multi-resistant tuberculosis].

PMID- 22401732
TI  - [Low HDL cholesterol or HDL hypofunction].

PMID- 22401733
TI  - [Proliferative mesangial lupus nephritis: description of a cohort of 27
      patients].
AB  - BACKGROUND AND OBJECTIVE: To describe our cohort of 27 biopsy-proven patients and
      their long-term follow-up, with special attention to prognostic factors. PATIENTS
      AND METHODS: Twenty seven patients were retrospectively collected. They were
      controlled in the Internal Medicine Department of the Bellvitge's Hospital
      (Spain) between 1974 and 2010. Evaluation was performed at one, 3 and 5 year
      follow-up. RESULTS: There were 22 women (81.5%). Mean age at onset of nephritis
      was 34.83 years (SD 13.45). Partial or complete remission was achieved by 21
      patients (80.77%) in the one-year follow-up, 22 patients (84.61%) in the third
      year follow-up and 21 patients (77.77%) in the fifth-year follow-up. A change in
      the histology class was diagnosed in 4 patients. Seven patients suffered flares
      of nephritis. Seven patients died in the long term follow-up, 3 out of this 7
      died because of systemic erythematosus lupus. CONCLUSION: Nephritis onset beyond
      45 years old is the factor mostly related with a poor prognosis. That is the
      reason why we recommend co-therapy with immunosuppressors from the beginning in
      such patients.

PMID- 22401734
TI  - [Responsibility for reporting adverse events: can notifying health professional
      be assured?].

PMID- 22401735
TI  - [Vaccinations in the Public Health Law: the 21 immunization schedules and so it
      goes].

PMID- 22401736
TI  - [Hyponatremia in elderly patients admitted in an acute geriatric care unit.
      prevalence and prognosis].
AB  - BACKGROUND AND OBJECTIVE: In order to analyze the prevalence of hyponatremia in
      in-hospital elderly patients and its prognosis factor value, we performed a
      transversal prospective study in an Acute Geriatric Unit (AGU). PATIENTS AND
      METHODS: Two hundred and sixty in-hospital patients were collected prospectively
      in an AGU. Sociodemographic and lab data were collected as well as the Barthel,
      Pfeiffer and Charlson tests. A questionnaire was performed in hospital.
      Hyponatremia was considered when the plasmatic sodium was <=134 mmol/l. RESULTS:
      The sample consisted of 137 women (52.7%) and 123 men (47.3%). Mean age was 83.6
      years (SD 7.9). Mean plasmatic sodium values were 137.3 mmol/l (range 112-168).
      Emergency lab tests showed 60 patients with hyponatremia (23.7%), 35 (13.6%) in
      the AGU. Cardiopulmonary were the most related diseases. Mean hospital length of
      stay was 12.8 days (SD 12.8). In-hospital mortality was 12.9%. We observed a
      statistic relationship between the presence of hyponatremia and a greater mean
      length of stay (15.53 vs 11.99 days, P=.003). No relationship was found between
      hyponatremia and mortality (15 vs 12.7%, P=.588). CONCLUSION: Hyponatremia in
      patients admitted in an AGU is a prevalent disorder related with a greater
      hospital length of stay, but not with mortality.

PMID- 22401737
TI  - [Changes in the European normative of clinical trials (ii): towards a
      proportional and risk-adapted regulation].

PMID- 22401738
TI  - [Preparing for retirement. An individual and medical college's responsibility].

PMID- 22401739
TI  - [Collaboration between primary healthcare and tertiary hospitals: a cost
      effective integral research model].

PMID- 22401740
TI  - [Analysis of TRPV1 gene polymorphisms in Spanish patients with neuropathic pain].
AB  - BACKGROUND AND OBJECTIVE: The vanilloid receptor TRPV1 is a molecular integrator
      of painful stimuli. Several recent studies suggest that TRPV1 may play a role in
      development and maintenance of chronic pain. In an attempt to determine if
      genotypic variations in TRPV1 gene could be involved in the susceptibility to
      suffer neuropathic pain we have studied genetic variants of human TRPV1 gene.
      PATIENTS AND METHODS: We have studied the distribution of Met315Ile and Ile585Val
      TRPV1 polymorphisms in a total of 440 Caucasian subjects: 232 patients with
      neuropathic pain and 208 healthy subjects matched by age and sex. The
      polymorphisms were analyzed with polymerase chain reaction (PCR) using TaqMan
      probes specific for each allele. RESULTS: Our results show that the distribution
      of Met315Ile and Ile585Val genotypes and alleles is similar in patients with
      neuropathic pain and in healthy subjects. However, the Met315Met genotype is more
      frequent in females diagnosed as suffering neuropathic pain. No differences were
      observed when we segregate the patients according to visual analogue scale
      values. CONCLUSIONS: The observation of differences in the distribution of
      Met315Ile TRPV1 genotypes only in females diagnosed of neuropathic pain suggests
      that this polymorphism, together with other physiological factors such as sex,
      may influence individual susceptibility to neuropathic pain.

PMID- 22401741
TI  - Latent tuberculosis in rheumatoid arthritis: evaluating cellular response and
      high-resolution computed tomography.
AB  - INTRODUCTION: The diagnosis of latent tuberculosis (LTB) in patients with
      rheumatoid arthritis (RA) has become important with the introduction of anti
      tumor necrosis factor (anti-TNF-alpha) agents and the appearance of active
      tuberculosis cases in these patients. The tuberculin skin test (TST) has limited
      value in patients with RA. Tests based on the release of interferon-gamma (IFN
      gamma) are being studied, but their role has not been well established for this
      group of patients. OBJECTIVES: To compare the diagnosis of LTB in patients with
      RA by using cellular immune response to the TST and T.SPOT-TB. Additionally,
      findings of tomography studies compatible with LTB were used. METHODS: Clinical
      evaluation, TST, T.SPOT-TB and high-resolution computed tomography (HRCT) in a
      group of patients with RA at the University Hospital of the Federal University of
      Goias. RESULTS: Response to the TST was lower in patients with RA (13.5%)
      compared to the predicted values of the general population. T.SPOT-TB identified
      a higher number of patients with LTB than the TST (36.8%). HRCT showed changes
      compatible with LTB in 52.9% of the patients, including 8 of the 11 patients with
      negative TST and T.SPOT-TB. CONCLUSIONS: The TST by itself is insufficient to
      diagnose LTB. A higher number of positive results were obtained with T.SPOT-TB
      when compared to the TST. Nevertheless, it was negative in a large percentage of
      patients with tomography findings consistent with LTB. HRCT is readily available
      in most large health-care centers and it could be incorporated into the
      diagnostic strategy for LTB in patients with RA.

PMID- 22401742
TI  - Pulmonary embolism due to metastatic papillary adenocarcinoma of the uterine
      cervix.

PMID- 22401743
TI  - Gonadal hormones and the control of reactive gliosis.
AB  - Astrocytes and microglia respond to central nervous system (CNS) injury with
      changes in morphology, proliferation, migration and expression of inflammatory
      regulators. This phenomenon is known as reactive gliosis. Activation of
      astrocytes and microglia after acute neural insults, such as stroke or traumatic
      CNS injury, is considered to be an adaptive response that contributes to minimize
      neuronal damage. However, reactive gliosis may amplify CNS damage under chronic
      neurodegenerative conditions. Progesterone, estradiol and testosterone have been
      shown to control reactive gliosis in different models of CNS injury, modifying
      the number of reactive astrocytes and reactive microglia and the expression of
      anti-inflammatory and proinflammatory mediators. The actions of gonadal hormones
      on reactive gliosis involve different mechanisms, including the modulation of the
      activity of steroid receptors, such as estrogen receptors alpha and beta, the
      regulation of nuclear factor-kappaB mediated transcription of inflammatory
      molecules and the recruitment of the transcriptional corepressor c-terminal
      binding protein to proinflammatory promoters. In addition, the Parkinson's
      disease related gene parkin and the endocannabinoid system also participate in
      the regulation of reactive gliosis by estradiol. The control exerted by gonadal
      hormones on reactive gliosis may affect the response of neural tissue to trauma
      and neurodegeneration and may contribute to sex differences in the manifestation
      of neurodegenerative diseases. However, the precise functional consequences of
      the regulation of reactive gliosis by gonadal hormones under acute and chronic
      neurodegenerative conditions are still not fully clarified.

PMID- 22401744
TI  - Partitioning of Cd and Pb in the blood of European blackbirds (Turdus merula)
      from a smelter contaminated site and use for biomonitoring.
AB  - Blood composition is commonly measured to assess exposure to and effects of
      metals on birds. In most of passerine species, only small volumes of blood may be
      sampled safely (<500 MUL), which limit the measure of several markers of health
      status and chemical residues. Here, we documented the partitioning of Cd and Pb
      in the blood of European Blackbirds Turdus merula in order to propose usable
      relationships between whole blood concentrations (for which toxicological
      benchmarks exist) and those measured in the erythrocytes. Sixty-two blackbirds
      were trapped along a pollution gradient (smelter of Metaleurop Nord, Northern
      France). Blood was sampled and Cd and Pb concentrations were measured both in
      whole blood and in the erythrocytes only. Birds coming from the most contaminated
      sites exhibited high residues for both Cd and Pb. We assessed that 73% and 99% of
      Cd and Pb, respectively, were associated to erythrocytes. Strong linear
      relationships, that were not influenced by neither the age nor the sex, were
      established between whole blood residues and those of erythrocytes for Cd and Pb
      (adj-R(2)=0.78 and 0.93, respectively). Present findings are promising to
      optimize the use of small blood samples in order to investigate several responses
      relative to wildlife health status.

PMID- 22401745
TI  - Comparison of organohalogen compounds in a white-tailed sea eagle egg laid in
      1941 with five eggs from 1996 to 2001.
AB  - Eggs laid by white-tailed sea eagles (Haliaeetus albicilla), one in 1941 and five
      eggs between 1996 and 2001, all from the same geographical region of the Baltic
      Sea, were screened for organohalogen substances. The 1941 egg contained
      hexachlorobenzene (HCB), but did not contain either of the pesticides
      hexachlorocyclohexane (HCH) or p,p'-DDT, nor any metabolites of the latter. In
      contrast, the more recent eggs (REs) contained all of these compounds. Of the
      seven polychlorinated biphenyls (PCBs) analyzed (CB28, -52, -101, -118, -138/
      163, -153 and 180), only the more highly chlorinated congeners were detected in
      the 1941 sample, with CB153 followed by CB180 showing the highest concentrations.
      All eggs demonstrated the same congener pattern with respect to the more highly
      chlorinated PCBs, but concentrations were approximately 70-230 times higher in
      the REs. All of the polychlorinated-p-dioxin and dibenzofuran (PCDD/Fs) congeners
      analyzed were detected in the eggs, with the dominant congener being 2,3,4,7,8
      PeCDF (1250pg/gl.w. in 1941 and 1540pg/gl.w. (GM) for the REs, respectively).
      None of the other congeners exceeded 400pg/gl.w., and the concentrations of
      2,3,7,8-TCDD, 2,3,7,8-TCDF and 1,2,3,7,8-PeCDF were all lower in the REs. None of
      five congeners of polybrominated diphenyl ethers (PBDEs) found in the REs was
      detected in the egg from 1941. The three methoxylated brominated diphenyl ethers
      (MeO-BDEs) analyzed were found at similar levels and with a similar congener
      pattern in REs as in the egg from 1941. In conclusion, this study has shown the
      absence of DDE and PBDE and the presence of HCB and PCBs in a white-tailed sea
      eagle egg laid in 1941, and a strong increase of PCBs, DDE and PBDE in white
      tailed sea eagle eggs from the same area in 1996-2001. The MeO-BDEs were found in
      similar concentrations in the analyzed eggs. The 1941 sample shows substantial
      concentrations of PCDD/Fs, noteworthy in the same magnitude as in the recent
      samples, illustrating the historical and recent exposure of these compounds.

PMID- 22401746
TI  - Enzymatic and microbial transformation assays for the evaluation of the
      environmental fate of diclofenac and its metabolites.
AB  - Diclofenac has been of environmental concern due to the potential harmful effects
      on non-target organisms at environmentally relevant concentrations. In this
      study, we evaluated the transformation kinetics of diclofenac and its two major
      metabolites in two laboratory-scale experiments: the transformation of diclofenac
      in the presence of rat liver S9 fraction with co-factors, and the transformation
      of diclofenac, 4'-hydroxy-diclofenac and diclofenac beta-O-acyl glucuronide in
      the inoculum used for the OECD 301C ready-biodegradability test. 4'-Hydroxy
      diclofenac was identified as the major phase I metabolite and diclofenac beta-O
      acyl glucuronide was identified as the major phase II metabolite in the S9 assay.
      Transformation of diclofenac in the microbial degradation test did not occur
      significantly for 28 d, whereas 4'-hydroxy-diclofenac degraded slowly, indicating
      that the biological removal of diclofenac is not likely to occur in conventional
      STPs unless sorptive removal is significant. However, diclofenac beta-O-acyl
      glucuronide deconjugated to form equimolar diclofenac within 7 d, in the
      microbial degradation test. The mixture of diclofenac and its two metabolites,
      formed after incubating diclofenac in S9 medium for 2 h, was spiked in the
      inoculum to link both assays. The concentrations of diclofenac and its
      metabolites, measured over time, agreed well with predicted values, using rate
      parameters obtained from independent experiments. The results show that phase II
      metabolites generated in mammals may deconjugate easily in conventional STPs to
      form a parent compound and that these processes should be considered during the
      environmental monitoring and risk assessment of diclofenac.

PMID- 22401747
TI  - PM(10)-bound polycyclic aromatic hydrocarbons: biological indicators, lung cancer
      risk of realistic receptors and 'source-exposure-effect relationship' under
      different source scenarios.
AB  - Cancer has become a critical health issue in the world heritage city Kandy, Sri
      Lanka. Polycyclic aromatic hydrocarbons (PAHs), one of persistent organic
      pollutants, in the atmosphere may be a major etiological factor in lung
      carcinogenicity. Over the very high concentrations of ambient air PAHs reported
      in Kandy, this paper is focused on setting priorities to control human exposure
      to PAHs in prevention of cancer. On re-appraisal of the classical indicator
      benzo(a)pyrene (B[a]P) for atmospheric PAHs-related carcinogenicity, B[a]P failed
      to reflect the toxicity completely and may not be the sole indicator for risk
      assessment studies in complex multi-sourced urban environments. The excess
      lifetime lung cancer risks of atmospheric PAHs with 'less than lifetime exposure'
      were assessed based on both 'B[a]P toxic equivalents' and 'B[a]P surrogate
      epidemiological' approach of risk quantification, over emissions characterized
      urban, suburban, and rural areas of Kandy. In urban heavy traffic areas, PAH
      related additional cancer burden has been 942 million(-1) over 30 y of exposure.
      Over the whole study area, ?p-PAHs show strong correlation (r=0.8) to the
      predicted risk levels. While the urban and suburban predicted cancer risk levels
      could not show significant correlation to their emission sources indicating the
      real complexity in mega urban environments, the rural lung cancer risk levels
      correlated perfectly with the source, firewood combustion. Policy decisions on
      environment and health could be based on established correlations among 'emission
      sources-exposures-health effects'. The priority for "analysis of options and
      policy formulation to reduce inhalation PAHs exposure of population in Kandy" was
      considered "moderate to high".

PMID- 22401748
TI  - Research performance of centers of expertise for rare diseases--the influence of
      network integration, internal resource access and operational experience.
AB  - OBJECTIVES: Centers of expertise (CoE) are vital to the care and treatment of
      patients with rare diseases and play a central role in generating medical and
      scientific knowledge. This study explores the relationship between a CoEs
      internal resource availability, operational experience and functional network
      integration and its research performance. METHOD: Hypotheses were tested based on
      a sample of 64 CoEs in Europe and North America that specialize in 6 rare
      diseases. We collected questionnaire data related to strategic and structural
      antecedents and subsequently examined bibliometric data in the ISI Web of Science
      database to determine (1) research output by publication counts and (2) research
      impact by the number of citations. RESULTS: A CoEs research performance is
      greatly determined by available experiences and internal resources as well as by
      the nature of networks. While research output increases with the number of
      treated patients, the amount of resources and access to R&D networks, the impact
      of the identified publications is not related to a CoEs availability of internal
      resources or to the size of its R&D network. Nevertheless, a CoEs focus on care
      oriented networks increases its research impact. CONCLUSION: Under the guidance
      of different national efforts, this study aims to support a nationwide
      establishment of specialized CoEs for rare diseases. It emphasizes the relevance
      of CoEs for the generation of medical knowledge for rare diseases as well as
      their need for essential support through internal and external resources. The
      findings further show the necessity for CoEs not only to concentrate on R&D
      collaborations to generate completely new knowledge and opportunities but also to
      establish networks with operational care partners such as general practitioners,
      local therapists, rehabilitation centers or other hospitals.

PMID- 22401749
TI  - Admission of drug-selling behaviors is structured by genetic and nonshared
      environmental factors: results from a longitudinal twin-based study.
AB  - Behavioral genetic research has consistently revealed that approximately one-half
      of the variance in antisocial behaviors is attributable to genetic factors. Even
      so, there is some reason to believe that different types of antisocial behaviors
      may have different developmental etiologies. The current study used this
      possibility as a springboard to examine the genetic and environmental influences
      on admission of drug-selling behaviors. Analysis of twin pairs drawn from the
      National Longitudinal Study of Adolescent Health revealed that 38% of the
      variance in a continuously coded drug-selling variable was accounted for by
      genetic factors and 69% of the variance in a dichotomously coded drug-selling
      variable was the result of genetic factors. The remaining variance for both
      measures was explained by nonshared environmental factors. The implications that
      these results have for drug research are discussed and avenues for future
      research are offered.

PMID- 22401750
TI  - Bloodstream infection with extended-spectrum beta-lactamase-producing
      Enterobacteriaceae at a tertiary care hospital in New Zealand: risk factors and
      outcomes.
AB  - OBJECTIVES: To define local risk factors and outcomes for bacteremia with
      extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) at a
      tertiary hospital in New Zealand. METHODS: Patients with ESBL-E bacteremia were
      compared to matched control patients with non-ESBL-producing Enterobacteriaceae
      bacteremia. Patients were matched by onset of bacteremia (community vs.
      hospital), site of blood culture collection (peripheral vs. via central line),
      and infecting organism species. RESULTS: Forty-four cases with matched controls
      were included. Eight- and 30-day mortality was higher in cases than controls (27%
      vs. 7%; p=0.011 and 34% vs. 11%, p=0.011). Twenty-one cases (48%) were community
      onset. Community-onset cases were associated with urinary tract infection,
      whereas hospital-onset cases were associated with central line infection,
      intensive care admission, and Enterobacter cloacae. Independent risk factors for
      ESBL-E bacteremia were fluoroquinolone exposure (odds ratio (OR) 6.56, 95%
      confidence interval (CI) 1.79-24), first-generation cephalosporin exposure (OR
      12.3, 95% CI 1.01-148), and previously-known colonization with ESBL-E (OR 46.2,
      95% CI 3.45-619). CONCLUSIONS: The association with fluoroquinolone exposure
      suggests that measures to reduce unnecessary use may be an effective preventative
      strategy. Known colonization with ESBL-E is a strong risk factor for ESBL-E
      bacteremia, and colonization status should be taken into consideration when
      choosing empirical therapy.

PMID- 22401751
TI  - Ultrasound-guided diffuse optical tomography (DOT) of invasive breast carcinoma:
      does tumour total haemoglobin concentration contribute to the prediction of
      axillary lymph node status?
AB  - OBJECTIVES: To prospectively study the ultrasound-guided near-infrared diffuse
      optical tomography (DOT) findings of the total haemoglobin concentration (THC)
      detected in invasive breast carcinomas and its contribution to the prediction of
      axillary lymph node (LN) status. METHODS: A total of 195 invasive breast
      carcinomas were prospectively studied with DOT before surgery. Lumpectomy or
      mastectomy with full axillary nodal dissection was performed. Tumour size and THC
      level were correlated with LN status by a logistic regression analysis. RESULTS:
      One hundred twenty-four patients (63.59%) was LN(-) and 71 (36.41%) was LN(+).
      The average THC was significantly higher in the LN(+) group than in the LN(-)
      group (252.94+/-69.19 MUmol/L versus 203.86+/-83.13 MUmol/L, P=0.01). A
      multivariate analysis showed an independent relationship between the probability
      of axillary metastasis, elevated THC level (P=0.01), and tumour size (P=0.001).
      The odds ratio with THC>=140 MUmol/L was 13.651 (1.781-104.560), whereas that of
      tumour size with a 1cm increment was only 1.777 (1.283-2.246). CONCLUSIONS: The
      THC level and the tumour size are independent and preoperative predictors of
      axillary nodal status; these variables may improve the diagnosis of patients with
      lymph node metastasis.

PMID- 22401753
TI  - Prevalence and predictors of benign lesions in renal masses smaller than 7 cm
      presumed to be renal cell carcinoma.
AB  - The present study was designed to determine the incidence and predictive factors
      of benign renal lesions in 450 patients who underwent surgical removal of
      solitary renal masses <7 cm in diameter. Of the 450 renal masses, 88 (19.9%) were
      benign lesions. Female sex, nephron-sparing surgery, surgery between 1990 and
      1996, cystic components on imaging, and small tumors (<4 cm) were independently
      associated with benign pathology. PURPOSE: To determine the association between
      preoperative parameters with final benign pathology in patients who underwent
      surgical removal of solitary renal masses <7 cm in diameter. MATERIALS AND
      METHODS: A database of 450 patients without metastatic disease who underwent
      radical nephrectomy or nephron-sparing surgery (NSS) for removal of renal masses
      <7 cm between January 1990 and December 2009 was reviewed. Age, sex, symptoms,
      year and type of surgery, solid or cystic appearance, and tumor size were
      analyzed as presumed predictors of benign pathology. Multivariate analysis was
      performed to identify parameters associated with benign pathology. RESULTS: In
      all, 88 (19.9%) of the tumors were benign, including 39 (8.7%) oncocytomas and 22
      (4.9%) angiomyolipomas. The benign lesion rate for tumors <=2, 2.1-4, and 4.1-7
      cm was 30.3%, 27.1%, and 12.5%, respectively (2P < .001). For the periods of 1990
      1996, 1997-2003, and 2004-2009, the frequency of benign tumors was 25%, 17.3%,
      and 18.4% (2P = .271), the incidental tumor rate was 48.1%, 60.4%, and 63.8% (2P
      = .027), mean tumor size was 5, 4.6, and 4.1 cm (2P < .001), and the NSS rate was
      28.8%, 43.2%, and 52.7% (2P < .001), respectively. Logistic regression analysis
      revealed that female sex, NSS, surgery between 1990 and 1996, cystic components
      on imaging, and small tumors (<4 cm) based on radiologic examination were
      independently associated with benign pathology (odds ratio [OR] = 3.26, 2.56,
      2.43, 2.41, and 1.96, respectively). CONCLUSIONS: The incidence of incidental and
      small tumors amenable to NSS increased over time. Female sex was the strongest
      predictor of benign pathology.

PMID- 22401754
TI  - Neuroendocrine differentiation in castration-resistant prostate cancer: a
      systematic diagnostic attempt.
AB  - BACKGROUND: Assessing the neuroendocrine (NE) pattern in castration-resistant
      prostate cancer (CRPC) may prove useful in selecting potential responders to
      target therapies such as somatostatin analogues. The aim of this study was to
      define a panel of markers or examinations appropriate to characterize NE
      differentiation (NED). METHODS: Forty-seven patients with CRPC underwent a
      systematic diagnostic attempt to characterize the NE phenotype using a plasma
      blood test for chromogranin A (CgA) and immunohistochemical staining of needle
      biopsy-obtained specimens (CgA, somatostatin receptor 2 [SSTR2], Ki-67, and
      androgen receptors). In a subgroup of 26 patients, somatostatin receptor
      scintigraphy using (111)In-DTPA-d-Phe octreotide (octreotide scintigraphy;
      Octreoscan, Covidien, Hazelwood, MO) was also performed. RESULTS: NED was found
      in 85.1% of patients (if serum CgA, tissular CgA, and tissular SSTR2 were
      considered separately: 54%, 67%, and 58%, respectively). Only 15% of the 26
      patient subgroup had an abnormal octreotide scintigraphy result. Although p-CgA
      and t-CgA were associated with more aggressive disease with a worse prognosis,
      patients with positive tissular SSTR2 staining had longer overall survival (OS).
      CONCLUSION: This systematic approach to explore the NED in a quite homogeneous
      group of patients with CRPC seems reproducible and appropriate. Further
      investigations are required to validate this panel and better characterize
      potential responders to targeted therapy.

PMID- 22401752
TI  - Role of bone architecture and anatomy in osteoarthritis.
AB  - When considering the pathogenesis of osteoarthritis (OA), it is important to
      review the contribution of bone in addition to the contribution of cartilage and
      synovium. Although bone clearly plays a role in determining the distribution of
      biomechanical forces across joints, which in turn plays a role in the initiation
      of OA, it has also more recently been appreciated that bone may contribute in a
      biological sense to the pathogenesis of OA. Far from being a static structure,
      bone is a dynamic tissue undergoing constant remodeling, and it is clear from a
      number of radiographic and biochemical studies that bone and cartilage
      degradation occurs hand in hand. Whether the initial instigating event in OA
      occurs in cartilage or bone is not known, but it is clear that bony changes occur
      very early in the pathogenesis of OA and often predate radiographic appearance of
      the disease. This review focuses on the structural variants of both hip and knee
      that have been associated with OA and the ultrastructural bone changes in these
      sites occurring in early OA pathogenesis. This article is part of a Special Issue
      entitled "Osteoarthritis".

PMID- 22401756
TI  - Infra-slow fluctuations in electrophysiological recordings, blood-oxygenation
      level-dependent signals, and psychophysical time series.
AB  - Converging electrophysiological and neuroimaging data show that mammalian brain
      dynamics are governed by spontaneous modulations of neuronal activity levels in
      cortical and subcortical structures. The time scales of these fluctuations form a
      continuum from seconds to tens and hundreds of seconds corresponding to slow (0.1
      1Hz), infra-slow (0.01-0.1Hz), and "ultradian" (<0.01Hz) frequency bands,
      respectively. We focus here on the spontaneous neuronal dynamics in the infra
      slow frequency band, infra-slow fluctuations (ISFs), and explore their
      electrophysiological substrates and behavioral correlates. Although
      electrophysiological ISFs and the associated infra-slow modulations of fast
      (here, >1Hz) neuronal activities have been recognized on numerous occasions since
      late 50's, a resurgence in interest towards this frequency band has been driven
      by a discovery that ISFs in blood-oxygenation-level dependent (BOLD) signals are
      correlated among specific constellations of brain regions, which constitute
      intrinsic connectivity networks and define the dynamic architecture of
      spontaneous brain activity at large. Importantly, electrophysiological and BOLD
      signal ISFs are directly correlated both with ISFs in amplitudes of fast neuronal
      activities and with ISFs in behavioral performance. Moreover, both
      electrophysiological and neuroimaging data suggest that the apparently scale-free
      ISFs may arise from more local quasi-periodic infra-slow oscillations with a
      contribution of time-scale-specific cellular-level mechanisms. We conclude that
      ISFs in electrophysiological recordings, BOLD signals, neuronal activity levels,
      and behavioral time series are likely to reflect the same underlying phenomenon;
      a superstructure of interacting and transiently oscillatory ISFs that regulate
      both the integration within and decoupling between concurrently active neuronal
      communities.

PMID- 22401755
TI  - Prediction of cognitive decline based on hemispheric cortical surface maps of
      FDDNP PET.
AB  - OBJECTIVES: A cross-sectional study to establish whether a subject's cognitive
      state can be predicted based on regional values obtained from brain cortical maps
      of FDDNP Distribution Volume Ratio (DVR), which shows the pattern of beta amyloid
      and neurofibrillary binding, along with those of early summed FDDNP PET images
      (reflecting the pattern of perfusion) was performed. METHODS: Dynamic FDDNP PET
      studies were performed in a group of 23 subjects (8 control (NL), 8 Mild
      Cognitive Impairment (MCI) and 7 Alzheimer's Disease (AD) subjects). FDDNP DVR
      images were mapped to the MR derived hemispheric cortical surface map warped into
      a common space. A set of Regions of Interest (ROI) values of FDDNP DVR and early
      summed FDDNP PET (0-6 min post tracer injection), were thus calculated for each
      subject which along with the MMSE score were used to construct a linear
      mathematical model relating ROI values to MMSE. After the MMSE prediction models
      were developed, the models' predictive ability was tested in a non-overlapping
      set of 8 additional individuals, whose cognitive status was unknown to the
      investigators who constructed the predictive models. RESULTS: Among all possible
      subsets of ROIs, we found that the standard deviation of the predicted MMSE was
      1.8 by using only DVR values from medial and lateral temporal and prefrontal
      regions plus the early summed FDDNP value in the posterior cingulate gyrus. The
      root mean square prediction error for the eight new subjects was 1.6. CONCLUSION:
      FDDNP scans reflect progressive neuropathology accumulation and can potentially
      be used to predict the cognitive state of an individual.

PMID- 22401757
TI  - Quantifying cerebellar atrophy in multiple system atrophy of the cerebellar type
      (MSA-C) using three-dimensional gyrification index analysis.
AB  - Multiple system atrophy of the cerebellar type (MSA-C) is a degenerative
      neurological disease of the central nervous system. This study employed a method
      named, "surface-based three-dimensional gyrification index" (3D-GI) to quantify
      morphological changes in normal cerebellum (including brainstem) and atrophied
      cerebellum, in patients with MSA-C. We assessed whether 3D-GI can exclude gender
      and age differences to quantify cerebellum and brainstem atrophy more accurately.
      Sixteen healthy subjects and 16 MSA-C patients participated in this study. We
      compared 3D-GI values and volumes in the cerebellum, based on T1-weighted MR
      images. We also compared the images of reconstructed 3D cerebellum gray matter
      (3D-CBGM) and cerebellum white matter (3D-CBWM) to detect the atrophied
      cerebellar region in MSA-C patients. The 3D-GI values were in a stable range with
      small variances, exhibiting no gender effect and no age-related shrinkage.
      Significantly lower 3D-GI values were exhibited in both CBGM and CBWM of the MSA
      C patients compared with healthy subjects, even in the early phases of the
      disease. Decreases in 3D-GI values indicated the degeneration of the cerebellar
      folding structure, exactly reflecting the morphological changes in cerebellum.
      The 3D-GI method based on CBGM resulted in superior discriminative accuracy
      compared with the CBGM volumetric method. Using the two-dimensional 3D-GI values,
      the K-means classifier can evidently discriminate the MSA-C patients from healthy
      subjects.

PMID- 22401758
TI  - Investigation of fMRI neurofeedback of differential primary motor cortex activity
      using kinesthetic motor imagery.
AB  - Functional MRI neurofeedback (fMRI NF) is an emerging technique that trains
      subjects to regulate their brain activity while they manipulate sensory stimulus
      representations of fMRI signals in "real-time". Here we report an fMRI NF study
      of brain activity associated with kinesthetic motor imagery (kMI), analyzed using
      partial least squares (PLS), a multivariate analysis technique. Thirteen healthy
      young adult subjects performed kMI involving each hand separately, with NF
      training targeting regions of interest (ROIs) in the left and right primary motor
      cortex (M1). Throughout, subjects attempted to maximize a laterality index (LI)
      of brain activity-the difference in activity between the contralateral ROI
      (relative to the hand involved in kMI) and the ipsilateral M1 ROI-while receiving
      real-time updates on a visual display. Six of 13 subjects were successful in
      increasing the LI value, whereas the other 7 were not successful and performed
      similarly to 5 control subjects who received sham NF training. Ability to
      suppress activity in the ipsilateral M1 ROI was the primary driver of successful
      NF performance. Multiple PLS analyses depicted activated networks of brain
      regions involved with imagery, self-awareness, and feedback processing, and
      additionally showed that activation of the task positive network was correlated
      with task performance. These results indicate that fMRI NF of kMI is capable of
      modulating brain activity in primary motor regions in a subset of the population.
      In the future, such methods may be useful in the development of NF training
      methods for enhancing motor rehabilitation following stroke.

PMID- 22401759
TI  - Contributions of dynamic venous blood volume versus oxygenation level changes to
      BOLD fMRI.
AB  - Blood-oxygenation-level-dependent (BOLD) fMRI has contributions from venous
      oxygenation and venous cerebral blood volume (CBV) changes. To examine the
      relative contribution of venous CBV change (DeltaCBV(v)) to BOLD fMRI, BOLD and
      arterial CBV changes (DeltaCBV(a)) to a 40-s forepaw stimulation in six alpha
      chloralose anesthetized rats were measured using a magnetization transfer-varied
      fMRI technique, while total CBV change (DeltaCBV(t)) was measured with injection
      of iron oxide nanoparticles. DeltaCBV(v) was obtained by subtracting DeltaCBV(a)
      from DeltaCBV(t). We observed a fast DeltaCBV(a) response with a time constant of
      2.9 +/- 2.3s and a slower DeltaCBV(v) response with a time constant of 13.5 +/-
      5.7s and an onset delay of 6.1 +/- 3.3s. These results are consistent with
      earlier studies under different anesthesia and stimulus, supporting that fast
      CBV(a) and slow CBV(v) responses are generalizable. Assuming the observed post
      stimulus BOLD undershoot is at least partly explained by the DeltaCBV(v)
      contribution, the relative contribution of the DeltaCBV(v)- and oxygenation
      change-related components to the BOLD response was estimated. The relative
      DeltaCBV(v) contribution increases with time during stimulation; whereby it is
      <0.14 during initial 10s and reaches a maximum possible value of ~0.45 relative
      to the oxygenation contribution during the 30-40s period after stimulus onset.
      Our data indicates that the contribution of venous oxygenation change to BOLD
      fMRI is dominant for short stimulations.

PMID- 22401760
TI  - Effects of image distortions originating from susceptibility variations and
      concomitant fields on diffusion MRI tractography results.
AB  - In this work we investigate the effects of echo planar imaging (EPI) distortions
      on diffusion tensor imaging (DTI) based fiber tractography results. We propose a
      simple experimental framework that would enable assessing the effects of EPI
      distortions on the accuracy and reproducibility of fiber tractography from a
      pilot study on a few subjects. We compare trajectories computed from two
      diffusion datasets collected on each subject that are identical except for the
      orientation of phase encode direction, either right-left (RL) or anterior
      posterior (AP). We define metrics to assess potential discrepancies between RL
      and AP trajectories in association, commissural, and projection pathways. Results
      from measurements on a 3 Tesla clinical scanner indicated that the effects of EPI
      distortions on computed fiber trajectories are statistically significant and
      large in magnitude, potentially leading to erroneous inferences about brain
      connectivity. The correction of EPI distortion using an image-based registration
      approach showed a significant improvement in tract consistency and accuracy.
      Although obtained in the context of a DTI experiment, our findings are generally
      applicable to all EPI-based diffusion MRI tractography investigations, including
      high angular resolution (HARDI) methods. On the basis of our findings, we
      recommend adding an EPI distortion correction step to the diffusion MRI
      processing pipeline if the output is to be used for fiber tractography.

PMID- 22401761
TI  - Suicidality and anxiety sensitivity in adults with HIV.
AB  - Suicide rates among HIV-positive individuals are more than three times higher
      than in the general population. Anxiety sensitivity (AS) may be clinically
      relevant to increasing our understanding of suicide among individuals with HIV.
      Specifically, relations between AS cognitive concerns and suicide related
      outcomes have been observed across a range of populations. The current
      investigation sought to examine the effect of AS and individual AS subfactors
      (i.e., cognitive, physical, and social concerns) in relation to suicidality in a
      sample of adults with HIV. Participants were 164 adults with HIV (17.1% women;
      mean age=48.40) recruited from AIDS service organizations in Vermont/New
      Hampshire and New York City. Findings from the current study indicate that AS
      cognitive concerns (beta=0.46, p=0.001), but not the global AS factor, are
      positively associated with elevated rates of suicidality among persons with HIV
      above and beyond demographics, HIV relevant factors, and negative affectivity.
      There was also a negative trend for AS physical concerns in terms of suicidality
      (beta=-0.25, p=0.07). Clinicians may benefit from implementing AS reduction
      strategies with HIV-positive persons who endorse elevated suicide risk as well as
      elevated AS cognitive concerns. The current study is limited by a cross-sectional
      design and lack of suicide attempt history. Future work would benefit from
      longitudinal examination of the observed relations, further inquiry regarding the
      relation between AS physical concerns and suicidality and a more comprehensive
      assessment of suicidality.

PMID- 22401762
TI  - Silent embolism after electrical cardioversion of atrial fibrillation: what does
      brain magnetic resonance imaging provide?

PMID- 22401763
TI  - Attenuation of airway hyperreactivity and T helper cell type 2 responses by
      coumarins from Peucedanum praeruptorum Dunn in a murine model of allergic airway
      inflammation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The root of Peucedanum praeruptorum Dunn (PPD) is
      a commonly used traditional Chinese medicine for the treatment of asthma. Its
      major constituents, coumarins, were presumed to be responsible for its efficacy.
      AIM OF THE STUDY: The potential of coumarins from PPD (CPPD) as anti-asthma agent
      was investigated. MATERIALS AND METHODS: Female BALB/c mice were sensitized and
      challenged with ovalbumin (OVA) to induce allergic airway inflammation. CPPD was
      administered intragastrically before every OVA challenge. Airway reactivity to
      the intravenous administration of acetylcholine chloride was measured 48h after
      final OVA inhalation. Airway inflammation was evaluated by leukocyte counts of
      bronchoalveolar lavage fluid (BALF) and histopathological analysis of lung
      lesions. Levels of interleukin (IL)-4, IL-5, IL-10, IL-13 and IFN-gamma in BALF
      and OVA-specific immunoglobulin (Ig) E in serum, and activity of eosinophil
      peroxidase (EPO) in lung was measured. The percentage of CD4(+)CD25(+)Foxp3(+)
      regulatory T cells among CD4(+) T cells in spleen was analyzed by flow cytometry.
      RESULTS: Compared with model group, CPPD significantly reduced airway
      hyperreactivity and airway eosinophilic inflammation, improved pathologic lesion
      of the lungs, reduced levels of IL-4, IL-5, IL-13 in BALF and OVA-specific IgE in
      serum, inhibited the activities of EPO in lung, and up-regulated levels of IL-10
      and IFN-gamma in BALF as well as the percentage of CD4(+)CD25(+)Foxp3(+)
      regulatory T cells in spleen. CONCLUSION: CPPD can significantly suppress OVA
      induced airway inflammation, airway hyperreactivity and Th2 predominant response
      in mice, showing great therapeutic potential for the treatment of allergic
      asthma.

PMID- 22401764
TI  - Puerarin exerts antipyretic effect on lipopolysaccharide-induced fever in rats
      involving inhibition of pyrogen production from macrophages.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Puerarin is the most abundant isoflavonoid in
      Radix Puerariae (Gegen), which has been prescribed as a medicinal herb for
      treating fever in China for a long history. AIM OF THE STUDY: The present study
      aimed at evaluating the antipyretic effect of puerarin and revealing the related
      mechanisms. MATERIALS AND METHODS: Lipopolysaccharide (LPS)-induced fever in rats
      was used to assess the antipyretic effect of puerarin. After an intraperitoneal
      injection of LPS (100MUg/kg), body temperature was tested every 30min up to 8h.
      Different doses of puerarin (25, 50, 100mg/kg) were intraperitoneally
      administered 30min before LPS injection. In vitro, LPS-stimulated RAW 264.7 cells
      were treated with various concentrations of puerarin (25-200MUM). The pyrogenic
      mediators, including interleukin-1beta (IL-1beta), tumor necrosis factor-alpha
      (TNF-alpha), interleukin-6 (IL-6), prostaglandin E(2) (PGE(2)) and nitric oxide
      (NO), were examined on both transcription and expression levels. Furthermore, the
      influences of the activation of nuclear factor-kappa B (NF-kappaB) and the
      phosphorylation of mitogen-activated protein kinases (MAPKs) by puerarin were
      assayed by western blot. RESULTS: The intraperitoneal administration of puerarin
      at test doses clearly demonstrated apparent antipyretic effect through the
      declines in body temperature elevated by LPS in rats. The in vitro data showed
      that puerarin inhibited the production of IL-1beta, TNF-alpha, IL-6, PGE(2) and
      NO; moreover, the RT-PCR analysis and the western blot analysis indicated that
      puerarin regulated the transcriptional level via suppression of NF-kappaB
      activation and blockade of MAPK signal pathway. CONCLUSIONS: In summary, the
      antipyretic property of puerarin might result, at least in part, from an
      inhibition of endogenous pyrogen production and expression. Taken in this sense,
      our findings provide an explanation for puerarin acting as an important
      constituent in Gegen, thus, provide scientific basis for the wide use of Radix
      Puerariae in China as a traditional antipyretic.

PMID- 22401765
TI  - Control of hypertension in rats using volatile components of leaves of Taxus
      chinensis var. mairei.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Taxus chinensis var. mairei
      (Taxaceae) is used traditionally to fill pillows in some rural areas of China.
      Its volatile substances have been speculated to be capable of improving sleep
      quality, making blood pressure stable, and having diuretic capacity as recorded
      in Ancient Chinese Materia Medica. Using animal models and new technologies, we
      confirmed the hypotensive potential of volatile components from leaves of Taxus
      chinensis var. mairei (VCLT). MATERIALS AND METHODS: VCLT was obtained by
      supercritical CO(2) extraction equipment from Taxus chinensis var. mairei fresh
      leaves. Hypertensive rats were pre-induced by intraperitoneal (i,p.) injection of
      Nomega-Nitro-l-Ariginine (l-NNA) for 15 days (15mg/kg, twice a day), then divided
      into 5 groups and subjected to the following treatments. l-NNA group (group 1)
      receiving l-NNA alone (15mg/kg, i.p., twice per day for 6 weeks); in addition to
      receiving l-NNA same as group 1, Hydrochlorothiazide (HDZ) group (group 2)
      receiving HDZ (orally administration, 5mg/kg, once per day for 6 weeks); VCLT
      groups (groups 3-5), including VCLT1, VCLT2, VCLT3. The VCLT rats were housed in
      an enclosed cage (2 rats/0.064m(3)). VCLT was mixed well and sprayed on fresh
      leaves surface of Taxus chinensis var. mairei (100ml/kg) with three dosages:
      167g/kg (VCLT1), 233g/kg (VCLT2) and 333g/kg (VCLT3), respectively. Systolic
      Blood Pressure (SBP), plasma nitric oxide (NO), plasma angiotensin II,
      postprandial blood glucose, fasting blood glucose and blood lipids were
      determined. RESULTS: VCLT prevented the increase of SBP and plasma angiotensin II
      in l-NNA treated rats. Although VCLT does not significantly reduce blood
      triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low density
      lipoprotein cholesterol (LDL-C), it decreases total cholesterol (TC) while
      increasing plasma NO levels in a dose-dependent manner. CONCLUSION: VCLT can be
      used as a natural and supplementary reagents for the treatment of hypertension.

PMID- 22401767
TI  - Novel protein of IBP from silkworm, Bombyx mori, involved in cytoplasmic
      polyhedrosis virus infection.
AB  - In the present study, the full-length cDNA of a novel insulin-related peptide
      binding protein (named BmIBP2) was identified from silkworm, Bombyx mori, using
      rapid amplification of cDNA ends. The full-length cDNA of BmIBP2 is 1293 bp,
      consisting of a 5'-terminal untranslated region (UTR) of 61 bp, and a 3'-UTR of
      335 bp with a poly-adenylation signal sequence AATAAA and a poly (A) tail. The
      BmIBP2 cDNA encodes a polypeptide of 298 amino acids, including an IG domain and
      an IGc2 domain, with a theoretical isoelectric point of 5.73 and a predicted
      molecular weight of 33.1 kDa. The BmIBP2 also has a signal peptide of 23 amino
      acids and a potential N-glycosylation site. The sequence similarity and
      phylogenic analysis indicated that BmIBP2 belongs to the group of invertebrates
      IBP and is closer to IGFBP7 than to the other IGFBPs in vertebrates. These
      findings suggest that BmIBP2 is a putative homolog of vertebrate endocrine factor
      IGFBP7 and has a functional similarity. By fluorescent quantitative real-time
      polymerase chain reaction, mRNA transcripts of BmIBP2 were mainly detected in the
      midgut but were hardly detectable in the hemocytes, vasa mucosa, fat body, silk
      gland, head, testicle, ovary, and spiracle. After the silkworm larvae were
      infected by B. mori cytoplasmic polyhedrosis virus (BmCPV), a significant up
      regulation in the relative expression level of BmIBP2 was found. All the results
      suggested that BmIBP2 is a novel protein that plays an important role in the
      insulin-signal pathway and in the immune response of silkworm to BmCPV infection.

PMID- 22401766
TI  - Inactivation of the budded virus of Autographa californica M nucleopolyhedrovirus
      by gloverin.
AB  - Antimicrobial peptides are generated in insects exposed to pathogens for
      combating infection. Gloverin is a small cationic antibacterial protein whose
      expression is induced in the hemocytes and fat body cells of Trichoplusia ni
      larvae exposed to bacteria. The purpose of this study was to determine the role
      of gloverin during baculovirus infection. We found that gloverin expression is
      induced in T. ni systemically infected with the baculovirus Autographa
      californica M nucleopolyhedrovirus (AcMNPV). Two gloverin genes were cloned using
      RNA isolated from the hemocytes of T. ni larvae that were systemically infected
      with AcMNPV budded virus (BV) and C-terminal 6x-His and V5 epitope tags were
      incorporated to facilitate gloverin isolation, detection and functional studies.
      The supernatants of Sf9 cells stably transfected with the two gloverin expression
      plasmids and affinity purified gloverin proteins reduced the quantity of
      infectious AcMNPV BV as measured in vitro by plaque assay with untransfected Sf9
      cells. Nanomolar concentrations of affinity column purified gloverin protein
      caused calcein to be rapidly released from unilamellar vesicles comprised of
      phosphatidylglycerol, but not from vesicles made up of phosphatidylcholine,
      suggesting that gloverin interaction with membranes is rapid and affected by
      membrane charge. Both the BV inactivation and calcein release activities of
      gloverin increased with higher concentrations of gloverin. These results
      demonstrate that gloverin is an antiviral protein that interacts with vesicle
      membranes to cause the contents to be released.

PMID- 22401768
TI  - Intimal thickening of meningeal arteries after serial corticectomies for
      Rasmussen encephalitis.
AB  - Rasmussen encephalitis is a rare cause of intractable epilepsy in children.
      Between 2008 and 2010, 4 patients had second cortical resections performed after
      a primary corticectomy for Rasmussen encephalitis. In each case, we observed some
      degree of vessel wall change in leptomeningeal arteries, consisting of moderate
      to moderately severe intimal hyperplasia. The intervals between original
      resection and second operation ranged from 8 months to 10 years. Ages of the
      patients ranged from 9 to 12 years at their first resection and from 10 to 19
      years at the time of revision. Four other Rasmussen encephalitis cases operated
      upon in the years 2006 to 2010 and 2 surgical revisions for severe cortical
      dysplasia, 1 for mild cortical dysplasia and 1 for recurrent dysembryoplastic
      neuroepithelial tumor, did not show significant vascular abnormalities (with
      surgical intervals of 10 months to 16 years). Leptomeningeal intimal hyperplasia
      appears to develop in the interval between repeated cortical resections for
      Rasmussen encephalitis, an inflammatory disorder. The pathogenesis of this
      vascular change may be related to meningeal inflammation in Rasmussen
      encephalitis. This finding in children undergoing surgical resection for
      Rasmussen encephalitis may itself lead to "secondary" ischemic change that
      contributes to worsening of epilepsy.

PMID- 22401769
TI  - Forkhead box P1 overexpression and its clinicopathologic significance in
      peripheral T-cell lymphoma, not otherwise specified.
AB  - Forkhead box P1 protein is a transcription factor involved in cell signaling and
      regulation of gene expression and is essential for B-cell development. Forkhead
      box P1 overexpression has been associated with a worsened prognosis in some B
      cell lymphomas. However, little is known about the clinicopathologic significance
      of forkhead box P1 in T-cell malignancies. In this study, immunohistochemistry
      for forkhead box P1 was performed in peripheral T-cell lymphoma, not otherwise
      specified, cases (n = 41), which were then divided into lower (n = 15) and higher
      (n = 26) forkhead box P1 expressers. Results of real-time quantitative reverse
      transcriptase polymerase chain reaction for forkhead box P1 messenger RNA
      supported the data on immunohistochemical forkhead box P1 expression. Forkhead
      box P1 overexpression in lymphoma cells was inversely associated with
      proliferation activity as evaluated by Ki-67 expression. Double immunostain for
      forkhead box P1 and a T-cell marker in normal lymph nodes showed forkhead box P1
      signals in many of nonneoplastic T cells. Prognostic analysis showed that
      forkhead box P1 overexpression was associated with an improved overall survival
      of the patients with peripheral T-cell lymphoma, not otherwise specified, and was
      independent of the International Prognostic Index in multivariate analysis.
      Forkhead box P1 overexpression may be associated with less activated phenotype of
      the tumors and with a better prognosis in patients with peripheral T-cell
      lymphoma, not otherwise specified. The clinicopathologic significance of forkhead
      box P1 overexpression in peripheral T-cell lymphoma, not otherwise specified, may
      be different from that in B-cell lymphomas.

PMID- 22401770
TI  - Sex-determining region Y-box 2 expression predicts poor prognosis in human
      ovarian carcinoma.
AB  - Sex-determining region Y-box 2 is proposed to be a key transcription factor in
      embryonic stem cells. The known roles of sex-determining region Y-box 2 in
      development and cell differentiation suggest that it is relevant to the aberrant
      growth of tumor cells. Thus, sex-determining region Y-box 2 may play an important
      role in tumor progression. However, its clinical significance in human ovarian
      carcinoma has been uncertain until recently. The aim of the present study was to
      clarify the clinical role of sex-determining region Y-box 2 expression in ovarian
      carcinoma. Immunohistochemical staining of 540 human ovarian carcinoma samples
      for sex-determining region Y-box 2 was performed using tissue microarray. The
      associations among sex-determining region Y-box 2 expression and clinical factors
      (diagnosis, tumor grade, International Federation of Gynecology and Obstetrics
      stage, and response to chemotherapy), overall survival, and disease-free survival
      were analyzed. We observed sex-determining region Y-box 2 expression in 15% of
      the ovarian carcinoma samples. Use of the Fisher exact test suggested that sex
      determining region Y-box 2 expression was associated with high-grade carcinoma (P
      = .009), especially high-grade serous carcinoma (P = .048); International
      Federation of Gynecology and Obstetrics stage (II-IV; P = .005); and malignant
      mixed mullerian tumors (P = .048). Sex-determining region Y-box 2 expression was
      also associated with decreased disease-free survival durations (P = .035; log
      rank test). Our results showed that sex-determining region Y-box 2 expression may
      be a potential marker related to tumor recurrence, as implicated by its role in
      cancer stem cells.

PMID- 22401772
TI  - Immunoglobulin G4-related coronary periarteritis in a patient presenting with
      myocardial ischemia.
AB  - Recent studies suggest that the cardiovascular system might be a possible target
      of immunoglobulin G4-related disease. Here we present a 66-year-old man who was
      admitted to our hospital because of chest symptoms suggestive of acute coronary
      syndrome. Besides luminal narrowing of the coronary arteries, marked periarterial
      thickening around the coronary artery was observed by computed tomography
      coronary angiography. Serum immunoglobulin G4 levels of this patient were
      elevated (564 mg/dL). The patient underwent coronary bypass surgery. After
      incision of the pericardium, a glittery white-yellowish, elastic-hard
      periarterial mass surrounding the left circumflex artery could be seen.
      Histologic analysis of the biopsy specimen showed the formation of lymphoid
      follicles and the presence of immunoglobulin G4-positive plasma cells; therefore,
      the diagnosis was immunoglobulin G4-related coronary periarteritis accompanied by
      physiologically significant myocardial ischemia.

PMID- 22401773
TI  - An interactive 3-D application for pain management: Results from a pilot study in
      spinal cord injury rehabilitation.
AB  - Research on pain following spinal cord injury (SCI) has revealed that patients
      not only experience several types of pain that could prove to be challenging to
      address, but also that each individual can interpret such pain in different
      subjective ways. In this paper we introduce a 3-D system for facilitating the
      efficient management of pain, and thus, supporting clinicians in overcoming the
      aforementioned challenges. This system was evaluated by a cohort of 15 SCI
      patients in a pilot study that took place between July and October 2010.
      Participants reported their experiences of using the 3-D system in an adapted
      version of the System Usability Scale (SUS) questionnaire. Statistically
      significant results were obtained with regards to the usability and efficiency of
      the 3-D system, with the majority of the patients finding it particularly useful
      to report their pain. Our findings suggest that the 3-D system can be an
      efficient tool in the efforts to better manage the pain experience of SCI
      patients.

PMID- 22401771
TI  - CD70 expression patterns in renal cell carcinoma.
AB  - CD70 is up-regulated in several malignancies, where it induces cytotoxic effects
      on B and T lymphocytes, leading to immune escape. Novel therapeutic agents
      targeting CD70 have entered clinical trials. We characterized expression of CD70
      protein in renal cell carcinoma specimens of various histologic subtypes and
      assessed their prognostic value and association with clinical/pathologic
      variables. We used tissue microarrays containing 330 cases using a novel
      fluorescent immunohistochemistry-based method of Automated Quantitative Analysis
      of in situ protein expression. The mean expression of CD70 was almost twice as
      high in tumors relative to normal tissue (P < .0001). When broken into subsets,
      CD70 was higher in sarcomatoid and clear cell tumors (P < .0001) and was variably
      elevated in oncocytomas and some papillary tumors. No association was found
      between CD70 expression and stage or grade. High CD70 expression was associated
      with decreased survival on univariate analysis in the clear cell subset of renal
      cell carcinoma; however, it did not retain significance on multivariate analysis.
      Given the elevated expression of CD70 in clear cell, sarcomatoid, and some
      papillary tumors, our findings suggest that CD70 might be a good drug target in
      renal cell carcinoma. Additional studies are warranted to assess the association
      between expression of CD70 and response to therapy with CD70-targeting drugs in
      renal cell carcinoma.

PMID- 22401774
TI  - "Stroke Nav": a wireless data collection and review system to support stroke care
      delivery.
AB  - "Stroke Nav" is a novel system to support the care of stroke patients. The system
      contains purpose-built web-based software to facilitate accurate near-real time
      data collection by clinicians throughout the complex care settings traversed by
      patients. Tools are included to facilitate pre-defined and bespoke data review
      with graphical dashboards showing performance metrics and other aggregate data.
      The software was designed collaboratively by health care professionals and
      engineers, and is accessible via the hospital intranet using desktop or laptop
      computers and wireless mobile devices. Stroke Nav is being routinely used in two
      hospitals, with over 1400 patients registered, and is now being introduced in
      other hospitals. The system is delivering benefits in relation to
      multidisciplinary communication, knowledge management, patient safety, clinical
      audit and service performance.

PMID- 22401775
TI  - [Chaos theory: a fascinating concept for oncologists].
AB  - The oncologist is confronted daily by questions related to the fact that any
      patient presents a specific evolution for his cancer: he is challenged by very
      different, unexpected and often unpredictable outcomes, in some of his patients.
      The mathematical approach used today to describe this evolution has recourse to
      statistics and probability laws: such an approach does not ultimately apply to
      one particular patient, but to a given more or less heterogeneous population.
      This approach therefore poorly characterizes the dynamics of this disease and
      does not allow to state whether a patient is cured, to predict if he will relapse
      and when this could occur, and in what form, nor to predict the response to
      treatment and, in particular, to radiation therapy. Chaos theory, not well known
      by oncologists, could allow a better understanding of these issues. Developed to
      investigate complex systems producing behaviours that cannot be predicted due to
      a great sensitivity to initial conditions, chaos theory is rich of suitable
      concepts for a new approach of cancer dynamics. This article is three-fold: to
      provide a brief introduction to chaos theory, to clarify the main connecting
      points between chaos and carcinogenesis and to point out few promising research
      perspectives, especially in radiotherapy.

PMID- 22401776
TI  - Inhibition of MMPs might increase anticancer properties of amniotic epithelial
      cells.

PMID- 22401777
TI  - An extension of hypotheses regarding rapid-acting, treatment-refractory, and
      conventional antidepressant activity of dextromethorphan and dextrorphan.
AB  - It was previously hypothesized that dextromethorphan (DM) and dextrorphan (DX)
      may possess antidepressant properties, including rapid and conventional onsets of
      action and utility in treatment-refractory depression, based on pharmacodynamic
      similarities to ketamine. These similarities included sigma-1 (sigma(1)) agonist
      and NMDA antagonist properties, calcium channel blockade, muscarinic binding,
      serotonin transporter (5HTT) inhibition, and MU receptor potentiation. Here, six
      specific hypotheses are developed in light of additional mechanisms and evidence.
      Comparable potencies to ketamine for DM and DX are detailed for sigma(1)
      (DX>DM>ketamine), NMDA PCP site (DX>ketamine>DM), and muscarinic
      (DX>ketamine>>>>DM) receptors, 5HTT (DM>DX?ketamine), and NMDA antagonist
      potentiation of MU receptor stimulation (DM>ketamine). Rapid acting
      antidepressant properties of DM include NMDA high-affinity site, NMDR-2A, and
      functional NMDR-2B receptor antagonism, sigma(1) stimulation, putative mTOR
      activation (by sigma(1) stimulation, MU potentiation, and 5HTT inhibition),
      putative AMPA receptor trafficking (by mTOR activation, PCP antagonism, sigma(1)
      stimulation, MU potentiation, and 5HTT inhibition), and dendritogenesis,
      spinogenesis, synaptogenesis, and neuronal survival by NMDA antagonism and
      sigma(1) and mTOR signaling. Those for dextrorphan include NMDA high-affinity
      site and NMDR-2A antagonism, sigma(1) stimulation, putative mTOR activation (by
      sigma(1) stimulation and beta adrenoreceptor stimulation), putative AMPA receptor
      trafficking (by mTOR activation, PCP antagonism, sigma(1) stimulation, beta
      stimulation, and MU antagonism), and dendritogenesis, spinogenesis,
      synaptogenesis, and neuronal survival by NMDA antagonism and sigma(1) and mTOR
      signaling. Conventional antidepressant properties for dextromethorphan and
      dextrorphan include 5HTT and norepinephrine transporter inhibition, sigma(1)
      stimulation, NMDA and PCP antagonism, and possible serotonin 5HT1b/d receptor
      stimulation. Additional properties for dextromethorphan include possible
      presynaptic alpha(2) adrenoreceptor antagonism or postsynaptic alpha(2)
      stimulation and, for dextrorphan, beta stimulation and possible muscarinic and MU
      antagonism. Treatment-refractory depression properties include increased
      serotonin and norepinephrine availability, PCP, NMDR-2B, presynaptic alpha-2
      antagonism, and the multiplicity of other antidepressant receptor mechanisms.
      Suggestions for clinical trials are provided for oral high-dose dextromethorphan
      and Nuedexta (dextromethorphan combined with quinidine to block metabolism to
      dextrorphan, thereby increasing dextromethorphan plasma concentrations).
      Suggestions include exclusionary criteria, oral dosing, observation periods, dose
      response approaches, and safety and tolerability are considered. Although oral
      dextromethorphan may be somewhat more likely to show efficacy through
      complementary antidepressant mechanisms of dextrorphan, a clinical trial will be
      more logistically complex than one of Nuedexta due to high doses and plasma level
      variability. Clinical trials may increase our therapeutic armamentarium and our
      pharmacological understanding of treatment-refractory depression and
      antidepressant onset of action.

PMID- 22401778
TI  - Novel therapies in benign and malignant bone diseases.
AB  - With an ageing population and improving cancer therapies, the two most common
      benign and malignant bone diseases, osteoporosis and bone metastases, will
      continue to affect an increasing number of patients. Our expanding knowledge of
      the molecular processes underlying these conditions has resulted in novel bone
      targets that are currently being explored in clinical trials. Clearly, the
      approval of denosumab, a monoclonal antibody directed against RANKL, has just
      marked the beginning of a new era for bone therapy with several additional new
      therapies lining up for clinical approval in the coming years. Potential agents
      targeting the osteoclast include cathepsin K, currently in phase 3 trials, and
      src inhibitors. Amongst anabolic agents, inhibitors of the Wnt-inhibitor
      sclerostin and dickkopf-1 are promising in clinical trials. Here, we will provide
      a comprehensive overview of the most promising agents currently explored for the
      treatment of bone diseases.

PMID- 22401779
TI  - Arcobacter bivalviorum sp. nov. and Arcobacter venerupis sp. nov., new species
      isolated from shellfish.
AB  - A group of ten Arcobacter isolates (Gram negative, slightly curved motile rods,
      oxidase positive) was recovered from mussels (nine) and from clams (one). These
      isolates could not be assigned to any known species using the molecular
      identification methods specific for this genus (16S rDNA-RFLP and m-PCR). The aim
      of this study is to establish the taxonomic position of these isolates. The 16S
      rRNA gene sequence similarity of mussel strain F4(T) to the type strains of all
      other Arcobacter species ranged from 91.1% to 94.8%. The species most similar to
      the clams' strain F67-11(T) were Arcobacter defluvii (CECT 7697(T), 97.1%) and
      Arcobacter ellisii (CECT 7837(T), 97.0%). On the basis of phylogenetic analyses
      with 16S rRNA, rpoB, gyrB and hsp60 genes, the mussel and clam strains formed two
      different, new lineages within the genus Arcobacter. These data, together with
      their different phenotypic characteristics and MALDI-TOF mass spectra, revealed
      that these strains represent two new species, for which the names Arcobacter
      bivalviorum (type strain F4(T)=CECT 7835(T)=LMG 26154(T)) and Arcobacter
      venerupis (type strain F67-11(T)=CECT 7836(T)=LMG 26156(T)) are proposed.

PMID- 22401780
TI  - Genetic polymorphisms of DNMT3L involved in hypermethylation of chromosomal ends
      are associated with greater risk of developing ovarian endometriosis.
AB  - Endometrioma is a common ovarian cyst associated with pain and infertility, but
      its pathogenesis remains enigmatic. Demonstration of the subtelomeric location of
      hypermethylation in endometrioma has been reported by genome-wide profiling of
      methylated promoters. Recently, rs113593938, a polymorphism in the DNA
      methyltransferase 3-like (DNMT3L) gene has been associated with subtelomeric
      hypomethylation. We investigated the association between endometrioma and
      rs113593938, rs8129776, rs7354779, and rs2276248, which were chosen for
      thoroughly covering the locus of interest. We enrolled 127 patients with
      histologically proved endometrioma and no associated deep endometriotic lesions
      and 317 healthy subjects for a case-control genetic association study. Genotyping
      was performed after PCR amplification of the region encompassing the
      polymorphisms, restriction enzyme digestion, and detection of fragments on an
      agarose gel. Differences in genotype and allele distributions between cases and
      controls were tested for each polymorphism separately using the chi(2) test. The
      rs8129776 was significantly associated with endometrioma (P = 0.003). Haplotype
      analysis showed a higher risk for the patients carrying the ACCC+T haplotypes for
      rs8129776, rs7354779, rs113593938, and rs2276248 (odds ratio, 7.15; 95% CI, 2.63
      to 19.44). We report, for the first time to our knowledge, the association of
      DNMT3L genetic variants and endometrioma; DNMT3L expression itself was not
      modified. Our study constitutes a first milestone toward a plausible role of
      DNMT3L in the establishment of specific DNA methylation patterns in endometrioma.

PMID- 22401781
TI  - The effect of time-under-tension and weight lifting cadence on aerobic,
      anaerobic, and recovery energy expenditures: 3 submaximal sets.
AB  - We examined the aerobic and anaerobic energy expenditures of weight lifting
      (bench press); submaximal work was kept constant among protocols. Ten male
      subjects (age, 23.2 +/- 3.1 years; height, 177.3 +/- 5.3 cm; weight, 82.1 +/-
      11.5 kg) were randomly assigned to 3 lifting sessions of 3 sets of 5 repetitions
      at 70% 1 repetition maximum (1RM) using 3 lifting cadences: 1.5 s down and 1.5 s
      up (15 s per set), 4 s down and 1 s up (25 s per set), and 1 s down and 4 s up
      (25 s per set). No differences were found among the aerobic exercise energy
      expenditures for each lifting cadence. However, anaerobic energy expenditure was
      significantly different among protocols: 1.5 down-1.5 up, 16.5 +/- 8.1 kJ; 4 down
      1 up, 21.6 +/- 8.1 kJ; and 1 down-4 up, 26.7 +/- 7.2 kJ (p = 0.001). Excess
      postexercise oxygen consumption (EPOC; after each set) was lower for 1.5 down-1.5
      up, 38.6 +/- 17.8 kJ; versus 4 down-1 up, 50.2 +/- 23.5 kJ; and 1 down-4 up, 50.0
      +/- 22.6 kJ (p = 0.002). Total energy expenditure also was significantly less for
      1.5 up-1.5 down, 60.2 +/- 23.8 kJ; versus 4 down-1 up, 80.0 +/- 27.7 kJ; and 1
      down-4 up, 84.2 +/- 28.3 kJ (p = 0.001). Differences in EPOC and total energy
      expenditure with submaximal lifting were based not on the amount of work
      performed or with a particular eccentric-concentric cadence, but on the time to
      completion of the weight lifting exercise - time-under-tension; longer submaximal
      lifting times had greater energy expenditure.

PMID- 22401782
TI  - Biological applications of synchrotron radiation infrared spectromicroscopy.
AB  - Extremely brilliant infrared (IR) beams provided by synchrotron radiation sources
      are now routinely used in many facilities with available commercial spectrometers
      coupled to IR microscopes. Using these intense non-thermal sources, a brilliance
      two or three order of magnitude higher than a conventional source is achievable
      through small pinholes (<10 MUm) with a high signal to-noise ratio. IR
      spectroscopy is a powerful technique to investigate biological systems and offers
      many new imaging opportunities. The field of infrared biological imaging covers a
      wide range of fundamental issues and applied researches such as cell imaging or
      tissue imaging. Molecular maps with a spatial resolution down to the diffraction
      limit may be now obtained with a synchrotron radiation IR source also on thick
      samples. Moreover, changes of the protein structure are detectable in an IR
      spectrum and cellular molecular markers can be identified and used to recognize a
      pathological status of a tissue. Molecular structure and functions are strongly
      correlated and this aspect is particularly relevant for imaging. We will show
      that the brilliance of synchrotron radiation IR sources may enhance the
      sensitivity of a molecular signal obtained from small biosamples, e.g., a single
      cell, containing extremely small amounts of organic matter. We will also show
      that SR IR sources allow to study chemical composition and to identify the
      distribution of organic molecules in cells at submicron resolution is possible
      with a high signal-to-noise ratio. Moreover, the recent availability of two
      dimensional IR detectors promises to push forward imaging capabilities in the
      time domain. Indeed, with a high current synchrotron radiation facility and a
      Focal Plane Array the chemical imaging of individual cells can be obtained in a
      few minutes. Within this framework important results are expected in the next
      years using synchrotron radiation and Free Electron Laser (FEL) sources for
      spectro-microscopy and spectral-imaging, alone or in combination with Scanning
      Near-field Optical Microscopy methods to study the molecular composition and
      dynamic changes in samples of biomedical interest at micrometric and
      submicrometric scales, respectively.

PMID- 22401783
TI  - Rituximab: an effective treatment for rheumatologic and digestive symptoms of
      celiac disease?

PMID- 22401784
TI  - Subclinical vascular disease in patients with systemic lupus erythematosus: the
      additive deleterious effect of the antiphospholipid syndrome.

PMID- 22401785
TI  - One case of Felty's syndrome efficiently treated with rituximab.
AB  - Felty's syndrome (FS) is a rare association of rheumatoid arthritis (RA),
      neutropenia and splenomegaly. Mechanisms of neutropenia in FS are unclear but
      involve both innate and humoral immunity, impaired granulopoiesis and decreased
      granulocyte half-life. Several treatments have been used without clear
      efficiency. We report a patient with FS efficiently treated with rituximab (RTX),
      the monoclonal anti-CD20 antibody. A literature review of FS treated with RTX was
      performed.

PMID- 22401786
TI  - Paracoccidioidomycosis: another cause of sternal osteomyelitis.

PMID- 22401787
TI  - Monitoring the performance of innovative and traditional biocides mixed with
      consolidants and water-repellents for the prevention of biological growth on
      stone.
AB  - In this study, some mixtures of consolidants or water-repellent products and
      biocides developed to prevent biological growth, were tested over time on three
      stone substrates with different bioreceptivity. The performance of both
      traditional (tetraethylorthosilicate, methylethoxy polysiloxane, Paraloid B72,
      tributyltin oxide, dibutyltin dilaurate) and innovative compounds (copper
      nanoparticles) was assessed using colour measurements, the water absorption by
      contact sponge method, and observation under stereo and optical microscopes. The
      application of the mixtures had also the purpose of controlling re-colonization
      on stone after a conservation treatment. The study site was the archaeological
      Area of Fiesole; the mixtures were applied in situ to sandstone, marble and
      plaster which had been cleaned beforehand. An innovative aspect of the study is
      that, by using non-invasive methods, it also permitted monitoring the mixtures'
      effectiveness in preventing biological growth. The monitoring results made it
      possible to assess the bioreceptivity of the treated stones (sandstone, marble,
      plaster) over a period of almost three years. The results showed that the
      mixtures of consolidants or water-repellent products with biocides were effective
      in preventing biological growth on both a substrate with low bioreceptivity like
      plaster and a substrate with high bioreceptivity such as marble. The innovative
      mixture of nano-Cu particles with a water-repellent yielded good results in terms
      of preventing biological colonization. Moreover, they apparently did not affect
      the substrates' colour. Mixtures of nano-Cu particles with a consolidant and a
      water-repellent hold great promise for preventing re-colonization of stone after
      conservation treatment.

PMID- 22401788
TI  - Effects of soil temperature and agitation on the removal of 1,2-dichloroethane
      from contaminated soil.
AB  - Mechanical soil aeration is an effective and low cost ex-situ remediation
      technique suitable for large sites contaminated by volatile organic compounds.
      However, this technique is still in the testing and development phase. To
      understand the effectiveness of this remediation technique and the main factors
      influencing its efficacy, an abandoned typical chlor-alkali chemical industry
      site was remediated using this technology on a pilot-scale. The results showed
      that this technology is effective for the remediation of volatile organic
      compounds, with a removal efficiency of greater than 99%. During the experiment,
      a better result was observed in the first 120 h than the last 120 h. Both
      temperature and agitation affected the remediation. Higher environmental or soil
      temperatures resulted in more rapid attenuation of 1,2-dichloroethane (1,2-DCA).
      Agitation had an obvious effect during the first 120 h. A preliminary dynamic
      characteristic study showed that the volatilization process can be described by a
      function similar to y=a+be((-kt)). Temperature (both environmental and soil
      temperature) had a greater effect on the reaction rate constant and the half-life
      of 1,2-DCA compared with agitation. This study aims to improve the remediation of
      contaminated sites, especially large areas contaminated by volatile organic
      contaminants.

PMID- 22401789
TI  - Sorption behavior of EE2 on soils subjected to different long-term organic
      amendments.
AB  - The transport and fate of hydrophobic organic contaminants in the environment
      involve complex phenomena that are influenced by many processes that include
      sorption by soil components. Sorption behavior of EE2 molecules onto different
      soil samples was studied and results correlated with the content and type of
      organic matter present. The highest K value, among all soils presented in this
      study, was obtained for soil fertilized with compost (1.22) which presented the
      highest organic carbon content. Also the sorption behavior depends greatly on the
      soil specific organic matter characteristics. A strong positive correlation was
      observed between aromatic and carboxylic units and K(OC) values. The results also
      suggested an association of the EE2 aromatic nuclei face to face with the surface
      and/or another EE2 molecule and also sorbent-sorbate interactions due to hydrogen
      or covalent bonding, likely to occur due to the presence of phenolic function at
      C-3 and hydroxyl function at C-17 of the EE2 molecules that can react with
      carboxylic functional groups of soil organic matter. The stronger EE2 sorbs to
      soil organic matter lower is the leaching into drinking water resources and
      runoff to rivers and surface water, minimizing its residual toxicity.

PMID- 22401790
TI  - Modelling in-stream temperature and dissolved oxygen at sub-daily time steps: an
      application to the River Kennet, UK.
AB  - The River Kennet in southern England shows a clear diurnal signal in both water
      temperature and dissolved oxygen concentrations through the summer months. The
      water quality model QUESTOR was applied in a stepwise manner (adding modelled
      processes or additional data) to simulate the flow, water temperature and
      dissolved oxygen concentrations along a 14 km reach. The aim of the stepwise
      model building was to find the simplest process-based model which simulated the
      observed behaviour accurately. The upstream boundary used was a diurnal signal of
      hourly measurements of water temperature and dissolved oxygen. In the initial
      simulations, the amplitude of the signal quickly reduced to zero as it was routed
      through the model; a behaviour not seen in the observed data. In order to keep
      the correct timing and amplitude of water temperature a heating term had to be
      introduced into the model. For dissolved oxygen, primary production from
      macrophytes was introduced to better simulate the oxygen pattern. Following the
      modifications an excellent simulation of both water temperature and dissolved
      oxygen was possible at an hourly resolution. It is interesting to note that it
      was not necessary to include nutrient limitation to the primary production model.
      The resulting model is not sufficiently proven to support river management but
      suggests that the approach has some validity and merits further development.

PMID- 22401792
TI  - Modeling an integrative oncology program within a community-centered oncology
      service in Israel.
AB  - OBJECTIVE: Describing the processes that preceded the opening of an integrative
      oncology program (IOP) within the oncology service (OS) of the largest health
      maintenance organization in northern Israel. METHODS: The groundwork towards
      initiation of the IOP was based on three key elements (1) Interviews with
      patients, practitioners and directors were performed in order to explore
      perspectives regarding complementary medicine integration (CM) within the OS; (2)
      review of research data on CM efficacy and safety in cancer care; (3) critical
      comparative analysis of seven models of IOPs in Israel, Europe, and the U.S.
      RESULTS: Ninety-three interviews included 24 patients, 34 conventional
      practitioners, 9 medical directors, and 26 CM-trained practitioners. The
      interviews revealed that there is a need for CM in the OS, aimed towards
      improving patients' well-being during chemotherapy and advanced disease. An
      integrative oncology score (IOS) was formulated based on 6 themes considered
      promoters of successful integration. CONCLUSIONS: Integration of CM within an
      oncology service should address patients' needs and research knowledge and be
      built upon mandatory practitioners' communication. PRACTICE IMPLICATIONS: IOP
      modeling necessitates in-depth study aimed at revealing the OS needs and
      expectations, adjusting research data to the OS clinical challenges, and
      tailoring an appropriate model of integrative care.

PMID- 22401791
TI  - A longitudinal study on engagement with dieting information as a predictor of
      dieting behavior among adults diagnosed with cancer.
AB  - OBJECTIVE: This study explores cancer survivors' engagement with information
      about dieting to control weight from doctors, interpersonal, and media sources
      and examines whether engagement from these sources impacts subsequent dieting
      behavior. METHODS: A total of 1128 respondents diagnosed with colorectal, breast,
      or prostate cancers were surveyed over three years following their cancer
      diagnoses. Using weighted logistic regression analyses, the authors predicted the
      odds of dieting based on earlier information engagement with sources, controlling
      for dieting in the previous year and confounders. RESULTS: Participants reported
      talking with doctors more frequently (37%) than seeking or scanning from
      interpersonal and media sources about dieting (15-22%). Seeking from
      interpersonal and media sources, and discussion with physicians, significantly
      predicted dieting behavior. In addition, discussions with physicians increased
      the odds of subsequent dieting behavior by 2.32 times (95% CI: 1.50-3.61;
      p=.002), over and above the effects of other information engagement. CONCLUSION:
      Cancer survivors reported engaging with a variety of information sources about
      dieting. Engagement with doctors and information-seeking from interpersonal or
      media sources predicted cancer survivors' dieting behavior a year later. PRACTICE
      IMPLICATIONS: The results may inform strategies to encourage and empower cancer
      survivors to engage with information about healthy lifestyle changes for
      promoting long-term health.

PMID- 22401793
TI  - Making data more meaningful: patients' views of the format and content of quality
      indicators comparing health care providers.
AB  - OBJECTIVE: Patient reported outcome measures (PROMs) are being used to inform
      national quality indicators for health care providers in England. Our objective
      was to explore patients' views of different formats and content of these data
      displays. METHODS: Six focus groups (N = 45) considered different formats
      (tables, bar charts, caterpillar and funnel plots) and content (uncertainty
      displays, volume of outcomes, color, icons, and ordering). A thematic analysis
      was carried out based on transcripts. RESULTS: Tables housing icons (star
      ratings) were the preferred display, having the most popular resonance and
      facilitating cognitive processing, appealing to most as the best format. Inferred
      meanings were overwhelmingly applied to unfamiliar formats (funnel plot) and
      content (uncertainty). Traffic light highlighting and using consistent and
      recognizable icons (five stars) helped understanding. Familiarity with the bar
      chart seemed to lend to false readings--error bars were not interpreted.
      CONCLUSION: Aspects of familiarity, meaningfulness (whether and how displays
      resonated with participants), and cognitive or choice processes informed views of
      displays. PRACTICE IMPLICATIONS: Tables with star ratings should be a primary
      display, ordered on statistical significance, including providers in the region
      plus England average. Caterpillar plots should be used to provide contextual
      information. More detailed numeric tables should also be accessible.

PMID- 22401794
TI  - Within-subject effect of coil-to-cortex distance on cortical electric field
      threshold and motor evoked potentials in transcranial magnetic stimulation.
AB  - Motor threshold (MT) is a global measure of corticospinal excitability in
      transcranial magnetic stimulation determined over the primary motor cortex. It is
      commonly quantified as stimulation intensity (SI(MT)) able to induce a muscle
      response over certain threshold amplitude after 5/10 consecutive stimuli. SI(MT)
      is known to be dependent on coil-to-cortex distance (CCD). Hypothetically, the
      effect of CCD on SI(MT) could be removed by using a computed estimate for the
      stimulus-induced maximum cortical electric field at MT level (EF(MT)). The CCDs
      of six volunteers were artificially increased by a maximum of 16.3+/-3.5mm in 5-7
      steps. At each CCD, the MT was estimated for the first dorsal interosseous muscle
      of the right hand as SI(MT) and EF(MT) as well as threshold curves. We found that
      SI(MT) correlated with CCD while EF(MT) did not. CCD had a significant effect on
      the within-subject variation in SI(MT) (F(6,28)=80.16, p<0.0001), but not in
      EF(MT) (F(6,28)=0.69, p=0.656) (analysis of variance). Furthermore, CCD had a
      minor, but significant within-subject effect on single-trial motor evoked
      potentials induced at different stimulation intensities, whereas the obvious
      major effect was caused by stimulation intensity. In conclusion, EF(MT) can be
      used as a measure of corticospinal excitability instead of SI(MT) to reduce the
      effect of within-subject variation in CCD.

PMID- 22401795
TI  - Intracranial hypertension prediction using extremely randomized decision trees.
AB  - Intracranial pressure (ICP) elevation (intracranial hypertension, IH) in
      neurocritical care is typically treated in a reactive fashion; it is only
      delivered after bedside clinicians notice prolonged ICP elevation. A proactive
      solution is desirable to improve the treatment of intracranial hypertension.
      Several studies have shown that the waveform morphology of the intracranial
      pressure pulse holds predictors about future intracranial hypertension and could
      therefore be used to alert the bedside clinician of a likely occurrence of the
      elevation in the immediate future. In this paper, a computational framework is
      proposed to predict prolonged intracranial hypertension based on morphological
      waveform features computed from the ICP. A key contribution of this work is to
      exploit an ensemble classifier method based on extremely randomized decision
      trees (Extra-Trees). Experiments on a representative set of 30 patients admitted
      for various intracranial pressure related conditions demonstrate the
      effectiveness of the predicting framework on ICP pulses acquired under clinical
      conditions and the superior results of the proposed approach in comparison to
      linear and AdaBoost classifiers.

PMID- 22401796
TI  - Identification of an ancient haemophilia A splice site mutation.
AB  - INTRODUCTION: To date, numerous mutations resulting in haemophilia A are known
      and recorded at HAMSTeRS. We identified a new splice site mutation in intron 6 of
      the F8 gene (T to G transition at position -14; c.788-14T>G) in seven not
      knowingly related patients, who all suffer from mild haemophilia A. RNA analysis
      of blood cells indicated that this mutation leads to the preferred generation of
      a transcript lacking the complete exon 7 (without frameshift). METHODS: To
      determine whether the mutation represented a founder mutation we analyzed
      intragenic (intronic) and extragenic short tandem repeat (STR) regions and
      constructed haplotypes in the 7 patients and 128 apparently healthy male control
      individuals. RESULTS: In the 128 healthy control individuals, 109 different
      haplotypes were found. Surprisingly, also the 7 patients carried 3 different
      haplotypes. However, by genealogy reconstruction using BATWING we could identify
      an ancestral haplotype on which the mutation apparently occurred. This haplotype 
      DXS9897:12-DXS1073:21-HA472:64-DXS1108:26 - was frequent and was found in three
      patients, but was also present in four control individuals who did not carry the
      splice site mutation. CONCLUSION: Our data indicate that the splice site mutation
      occurred in an individual carrying a relatively common haplotype. While the
      mutation was passed on through generations, the haplotypes identified in the
      seven patients derived from this founder haplotype but were changed by later
      mutations in the STR regions.

PMID- 22401797
TI  - Pennogenin tetraglycoside stimulates secretion-dependent activation of rat
      platelets: evidence for critical roles of adenosine diphosphate receptor signal
      pathways.
AB  - BACKGROUND: Total steroidal saponins extracted from the rhizome of Paris
      polyphylla Sm. var. yunnanensis (TSSPs) have been demonstrated to promote
      hemostasis in vivo and induce platelet aggregation in vitro. Pennogenin
      tetraglycoside (Tg) has been identified as one of the active ingredients in TSSPs
      and can induce rat platelet aggregation. OBJECTIVE: To investigate the functional
      role of Tg in platelets and the signaling pathway mechanisms which mediate Tg
      induced platelet aggregation. METHODS AND RESULTS: Using scanning electron
      microscopy, the turbidimetric method and flow cytometry, we demonstrated that Tg
      induces shape change and concentration-dependently induces aggregation, dense
      granule secretion and a-granule secretion in rat platelets. The activation
      characteristics were comprehensively confirmed using transmission electron
      microscopy. Apyrase and antagonists of the platelet adenosine diphosphate (ADP)
      receptors, P2Y1 and P2Y12, completely inhibited Tg-induced platelet aggregation,
      which was not sensitive to indomethacin or SQ29548 inhibition. Furthermore, ADP
      receptor antagonists inhibited Tg-induced a-granule secretion, and blockade of
      the P2Y1 receptor prevented Tg-induced platelet shape changes. Tg-induced dense
      granule secretion was not affected by ADP receptor antagonists or various various
      pharmacological inhibitors of the intracellular effectors involved in dense
      granule secretion signaling pathways. CONCLUSION: We identified that Tg directly
      induces platelet activation and demonstrated that Tg-induced platelet activation
      depends on dense granule secretion of ADP, which in turn activates the P2Y1 and
      P2Y12 receptor signaling pathways.

PMID- 22401798
TI  - Role of thiol pathways in TF procoagulant regulation.
AB  - The generation of procoagulant Tissue Factor (TF) is crucial for thrombosis. TF
      contains a surface exposed allosteric disulfide bond that stabilizes the carboxyl
      terminal domain involved in ligand interactions with coagulation factors VIIa and
      X. TF procoagulant activation typically occurs following cellular perturbations
      that also cause the appearance of procoagulant phosphatidylserine in the outer
      leaflet of cell membranes. However, thiol modifying agents, without suppressing
      phosphatidylserine exposure, can prevent TF activation, implicating thiol
      disulfide exchange reactions in the regulation of TF procoagulant activity of
      primary cells. Protein disulfide isomerase (PDI), a regulator of extracellular
      thiol exchange, is associated with cell surface TF and required for TF-dependent
      thrombosis in vivo. PDI regulates the thiol-dependent biogenesis of procoagulant
      microparticles that are released from myeloid cells and smooth muscle cells
      following activation of the purinergic P2X7 receptor. Genetic deletion of P2X7
      signaling attenuates FeCl(3)-induced carotid artery thrombosis in mice,
      indicating that TF prothrombotic activity is regulated by specific cell signaling
      pathways in vivo.

PMID- 22401799
TI  - Tissue factor controversies.
AB  - Tissue factor plays a primary role in both hemorrhage control and thrombosis
      depending upon whether its presentation is extravascular or intravascular. The
      molecular architecture and function of the tissue factor molecule and its role in
      the activations of factor IX and factor X have been elegantly elucidated but
      controversies prevail with respect to distinctions between tissue factor sources
      and tissue factor "activity." This presentation will review data on the
      architecture and functions of the tissue factor-factor VIIa complex and discuss
      the elements of the controversies associated with tissue factor presentation in
      both normal and pathologic milieu.

PMID- 22401800
TI  - Decryption of tissue factor.
AB  - Tissue factor (TF) is a transmembrane protein which, in complex with factor
      (F)VIIa, initiates blood coagulation. Numerous studies have determined TF
      epitopes and individual amino acids which play an important role in the TF/FVIIa
      complex formation and its activity towards natural substrates. However the
      subject of cell-surface TF activity remains controversial. It has been almost
      commonly accepted that TF on the cell surface has low (if any) activity, i.e. is
      encrypted and requires specific conditions/reagents to become active, i.e.
      decrypted. One of the leading theories suggests that cell membrane lipid
      composition plays a crucial role in TF decryption, whereas another assigns the
      key role to the formation of the Cys(186)-Cys(209) disulfide bond. Despite a
      number of studies published from several laboratories, the role of this bond in
      the activity of the TF/FVIIa complex remains elusive and controversial. One of
      the causes of this controversy could be related to the lack of specificity of the
      reagents used for the cell treatment leading to possible alterations in other
      cell surface proteins and cell membrane environment. In conclusion, the influence
      of the Cys(186)-Cys(209) this bond on cell surface TF function remains unclear.

PMID- 22401801
TI  - Dried blood spots versus plasma for the quantitation of HIV-1 RNA using a real
      Time PCR, m2000rt assay.
AB  - High costs and stringent requirements for storage and transport of plasma, often
      prohibit the availability of HIV viral load quantification in resource-limited
      settings. Dried blood spots (DBS) represent a better method of specimen
      collection that removes many of these logistical and technical limitations. The
      present study aimed to assess the performance of the Abbott m2000rt assay for
      quantitation of HIV-1 RNA in DBS specimens using plasma as a "gold standard" for
      comparison. One hundred paired DBS and plasma specimens were collected from
      patients infected with HIV, who were 18 years and older during routine visits to
      a private tertiary-care clinic in Chennai, India. HIV-1 RNA was extracted
      manually and then detected using the m2000rt assay. The mean plasma and DBS viral
      loads were 4.27 (95% CI: 2.65, 5.88) and 4.14 (95% CI: 1.96, 6.32) log copies/mL,
      respectively. The overall sensitivity of DBS reached 95%; with sensitivities of
      62%, 88% and 100% when stratified by viral load ranges of <=1000, 1000-3000 and
      >3000 copies/mL, respectively. An over quantitation of the viral load with DBS
      was observed in pairs with plasma viral load<3000 copies/mL [d=-0.3 log copies/mL
      (ranging from -0.1 to 0.6 log copies/mL)]. The study showed a strong concordance
      in RNA levels between plasma and DBS. The use of DBS specimens should be
      considered for HIV monitoring and for detection of virologic failure in resource
      limited settings.

PMID- 22401802
TI  - The enhancement of RNAi against HIV in vitro and in vivo using H-2K(k) protein as
      a sorting method.
AB  - Gene therapy offers a potentially an effective treatment for many human diseases,
      including HIV/AIDS. One of the most studied gene delivery systems is the use of
      lentivirus based vectors, which can deliver genes into both dividing and
      nondividing cells. However, low infection efficiency represents an obstacle for
      proper evaluation of their biological function. In this study, a recombinant
      lentiviral vector which expressed short hairpin RNAs (shRNAs) targeted against
      the HIV-1 vif/pol was transduced into various cells. An MHC class I molecule, H
      2K(k), was used as a marker to accumulate the virally transduced cells through
      immunomagnetic sorting. In vitro testing of transduced cells showed 85%
      suppression of HIV in post-sorted PBMCs compared to 30% in pre-sorted PBMCs. In
      additional, using a mouse xenotransplantation model with the same treatment
      protocol for cell enrichment, a >95% decrease in HIV activity in post-sorted
      cells was achieved, as compared to nearly none in the pre-sorted cells. These
      studies offer a practical method to accumulate virally transduced cells, which
      can be applied to evaluate the performance of various shRNAs constructs.

PMID- 22401804
TI  - Curcumin bioavailability from enriched bread: the effect of microencapsulated
      ingredients.
AB  - Human bioavailability of curcumin from breads enriched with 1 g/portion of free
      curcumin (FCB), encapsulated curcumin (ECB), or encapsulated curcumin plus other
      polyphenols (ECBB) was evaluated. Parental and metabolized curcuminoids and
      phenolic acids were quantified by HPLC/MS/MS in blood, urine, and feces collected
      over 24 h. The concentrations of serum curcuminoids were always below 4 nmol/L
      and those of glucuronides 10-fold less. Encapsulation delayed and increased
      curcuminoid absorption as compared to the free ingredient. Serum and urinary
      concentrations of ferulic and vanillic acid were between 2- and 1000-fold higher
      than those of curcuminoids, with ECBB eliciting the highest amounts. Fecal
      curcuminoids were 6-fold more abundant after ECB than FCB, while phenolic acids
      after ECBB quadruplicated those after ECB. Curcuminoid encapsulation increased
      their bioavailability from enriched bread, probably preventing their
      biotransformation, with combined compounds slightly reducing this effect.
      Phenolic acids are the major metabolites of curcuminoids and may contribute to
      their biological properties.

PMID- 22401803
TI  - Neighborhoods and systemic inflammation: high CRP among legal and unauthorized
      Brazilian migrants.
AB  - We estimate cross-sectional associations of neighborhood-level disorder,
      socioeconomic characteristics and social capital with individual-level systemic
      inflammation, measured as high C-reactive protein (CRP), using Boston
      Metropolitan Immigrant Health & Legal Status Survey (BM-IHLSS) data-a sample of
      relatively young, healthy foreign-born Brazilian adults. Logistic regression
      analyses suggest high CRP is positively associated with neighborhood disorder and
      negatively related to neighborhood social capital. Although we find no
      significant associations between other neighborhood socioeconomic variables and
      high CRP; males, those who were born in an urban area and those who had been
      graduated from high school were less likely to have had high CRP. Unauthorized
      Brazilian adults, those who smoked cigarettes daily and those who had a higher
      body mass index were more likely to have had high CRP. Our findings suggest that
      investigating sociogeographic stressors and social support may be important for
      understanding physiological dysregulation even among relatively healthy U.S. sub
      populations.

PMID- 22401805
TI  - Novel anti-HIV-1 activity produced by conjugating unsulfated dextran with polyL
      lysine.
AB  - A conjugate of polyL-lysine (PLL) with unsulfated dextran produced by reductive
      amination was found to have remarkable anti-HIV-1 activity against both the
      macrophage-tropic R5 virus Ba-L and T-cell line tropic X4 virus IIIB strains,
      although neither PLL nor dextran has such activity. The conjugate is a
      pseudoproteoglycan (pseudoPG) that simulates the structure of a proteoglycan.
      Conjugation with dextran was found to produce an antiviral effect in three kinds
      of assay systems including a human CD4(+) T-cell line, and the pseudoPG
      synthesized using 10 kDa PLL and 10 kDa dextran showed EC(50) 4-40 times lower
      than that of sulfated dextran or heparin against Ba-L and EC(50) equal to that
      against IIIB, indicating that PLL-dextran (PLL-Dex) was more effective against R5
      virus than sulfated polysaccharides. PLL-Dex significantly suppressed a
      clinically isolated R5 virus from primary peripheral blood mononuclear cells. PLL
      Dex interacted with the virus during adsorption to the cell and also decreased
      virus entry into the cell, suggesting PLL-Dex has multiple preventive mechanisms
      against HIV-1.

PMID- 22401806
TI  - Induction of type I interferon by high-molecular poly-gamma-glutamate protects
      B6.A2G-Mx1 mice against influenza A virus.
AB  - In addition to development of vaccines and synthetic antiviral drugs, recent
      studies have advocated the use of natural substances that inhibit or prevent
      viral infections. High-molecular-weight poly-gamma-glutamate (HM-gamma-PGA)
      produced by Bacillus subtilis chungkookjang was evaluated for anti-influenza
      virus activity. HM-gamma-PGA induced type I interferons (IFNs), which in turn
      stimulated expression of Myxovirus resistant 1 protein and IFN-related proteins
      in vitro. In the B6.A2G-Mx1 mouse model, which mimics the innate immune system of
      humans, treatment with HM-gamma-PGA enhanced the antiviral state of mice and
      protected them against highly pathogenic influenza A virus. Naturally synthesized
      HM-gamma-PGA has potent anti-influenza activity and may be a useful means for
      control of influenza virus.

PMID- 22401808
TI  - Fifteen years of Gamma Knife surgery for trigeminal neuralgia in the Journal of
      Neurosurgery: history of a revolution in functional neurosurgery.

PMID- 22401809
TI  - Localization of B4GALNT2 and its role in mouse embryo attachment.
AB  - OBJECTIVE: To investigate the location of beta-1,4-N
      acetylgalactosaminyltransferase II (B4GALNT2) and the involvement of this protein
      and Sd(a) antigen in embryonic implantation. DESIGN: Cell and animal study.
      SETTING: University. ANIMAL(S): Adult outbred Institute for Cancer Research mice.
      INTERVENTION(S): B4GALNT2 antibody injected into the uteri of mice in early
      pregnancy; E3.5 blastocysts and pregnant uterine tissues were collected. MAIN
      OUTCOME MEASURE(S): Protein expression was detected by immunofluorescence
      staining and Western blotting. Embryo attachment was assayed via in vitro and in
      vivo embryo implantation models. RESULT(S): The b4galnt2 gene expression in the
      293T cell line showed the protein localized in the plasma membrane. We confirmed
      that B4GALNT2 was localized on the surface of E3.5 blastocysts but was an
      intracellular component in uterine epithelia. Finally, anti-B4GALNT2 and lectins
      inhibition assays demonstrated the involvement of B4GALNT2 and Sd(a) antigen in
      embryonic attachment in vitro and in vivo via the mouse system and human
      endometrial cell line (Ishikawa). CONCLUSION(S): B4GALNT2 expressed in the
      blastocyst may interact with a ligand on the endometrial surface, perhaps via
      Sd(a) also, to permit embryo implantation. Our data suggest that B4GALNT2 and
      Sd(a) antigen are essential for embryo implantation.

PMID- 22401810
TI  - Assessment of FSHR variants and antimullerian hormone in infertility patients
      with a reduced ovarian response to gonadotropin stimulation.
AB  - OBJECTIVE: To study women with a poor response to ovarian hormone stimulation,
      known as low responders. Genetic defects in the FSH receptor gene (FSHR) were
      analyzed as well as antimullerian hormone (AMH) for ovarian reserve. DESIGN:
      Retrospective cohort study. SETTING: University hospital. PATIENT(S): Two hundred
      fifty-nine patients total: 74 low responders; 88 patients receiving assisted
      reproduction therapy (ART) with a normal ovarian response; and 97 women with a
      normal fertility status. INTERVENTION(S): DNA from patients was analyzed using
      real-time polymerase chain reaction. Serum concentrations of AMH were assessed
      using ELISA. MAIN OUTCOME MEASURE(S): The FSHR variants Asn680Ser (rs6166),
      Ala189Val (rs121909658), Ile160Thr (rs121909659), Thr449Ile (rs28928870) and the
      serum AMH concentrations were assessed. RESULT(S): With the exception of the
      frequent Asn680Ser polymorphism, no homozygotic SNPs of FSHR were found. In the
      group of ART patients, Thr160/Ile160 variants were more frequent in comparison
      with women with normal fertility. The Ser680/Ser680 was more frequent in ART
      patients than in women with normal reproductive function. The rate of live births
      was markedly reduced, particularly in the low responder group. No difference was
      noted in the distribution of the Ala189Val and Thr449Ile variant. Low serum AMH
      values were observed in 75% of the low responder group. CONCLUSION(S): FSHR gene
      variations such as Asn680Ser, Ala189Val, Thr449Ile, and Ile160Thr did not seem to
      be a decisive factor of poor response to fertility treatment, whereas the low
      ovarian reserve determined by AMH is considered more crucial.

PMID- 22401811
TI  - Efficiency of slush nitrogen vitrification of human oocytes vitrified with or
      without cumulus cells in relation to survival rate and meiotic spindle
      competence.
AB  - OBJECTIVE: To evaluate the efficiency of slush nitrogen vitrification of human
      oocytes with or without cumulus cells in terms of survival rate and maintenance
      of meiotic spindle. DESIGN: Randomized, comparative study. SETTING: Medical
      center. PATIENT(S): A total of 274 oocytes obtained from 46 couples undergoing
      infertility treatment. INTERVENTION(S): Metaphase II oocytes were divided into
      groups A and B, vitrified with and without cumulus cells, respectively. MAIN
      OUTCOMES MEASURE(S): Survival rates and maintenance of meiotic spindle observed
      immediately after warming and 3 hours after incubation. RESULT(S): No
      statistically significant difference was detected between the two groups in terms
      of survival rate, but a significantly higher percentage of detectable spindle was
      observed in group B (completely denuded oocytes), either immediately after
      warming or 3 hours after incubation. CONCLUSION(S): Complete denudation of
      oocytes before slush nitrogen vitrification does not influence survival rates but
      positively affects oocyte meiotic spindle competence. These data support the
      hypothesis that cumulus cells during vitrification represent an obstacle to
      cryoprotectant penetration more than having a protective role for the oocyte.

PMID- 22401813
TI  - Systemic elevation of PTEN induces a tumor-suppressive metabolic state.
AB  - Decremental loss of PTEN results in cancer susceptibility and tumor progression.
      PTEN elevation might therefore be an attractive option for cancer prevention and
      therapy. We have generated several transgenic mouse lines with PTEN expression
      elevated to varying levels by taking advantage of bacterial artificial chromosome
      (BAC)-mediated transgenesis. The "Super-PTEN" mutants are viable and show reduced
      body size due to decreased cell number, with no effect on cell size.
      Unexpectedly, PTEN elevation at the organism level results in healthy metabolism
      characterized by increased energy expenditure and reduced body fat accumulation.
      Cells derived from these mice show reduced glucose and glutamine uptake and
      increased mitochondrial oxidative phosphorylation and are resistant to oncogenic
      transformation. Mechanistically we find that PTEN elevation orchestrates this
      metabolic switch by regulating PI3K-dependent and -independent pathways and
      negatively impacting two of the most pronounced metabolic features of tumor
      cells: glutaminolysis and the Warburg effect.

PMID- 22401814
TI  - North Korean refugee health in South Korea (NORNS) study: study design and
      methods.
AB  - BACKGROUND: Understanding the health status of North Korean refugees (NKRs), and
      changes in health during the resettlement process, is important from both the
      humanitarian standpoint and the scientific perspective. The NOrth Korean Refugee
      health iN South Korea (NORNS) study aims to document the health status and health
      determinants of North Korean refugees, to observe various health outcomes as they
      occur while adapting to the westernized lifestyle of South Korea, and to explain
      the mechanisms of how health of migrants and refugees changes in the context of
      new environmental risks and opportunities. METHODS: The NORNS study was composed
      of an initial survey and a follow-up survey 3.5 years apart. Participants were
      recruited voluntarily among those aged 30 or more living in Seoul. The survey
      consists of a health questionnaire and medical examination. The health
      questionnaire comprises the following six domains: 1) demographic and migration
      information 2) disease history, 3) mental health, 4) health-related lifestyle, 5)
      female reproductive health, and 6) sociocultural adaptation. The medical
      examination comprises anthropometric measurements, blood pressure and
      atherosclerosis, and various biochemical measurements. Prevalence of several
      diseases able to be diagnosed from the medical examination, the changes between
      the two surveys, and the association between the outcome and other measurements,
      such as length of stay and extent of adaptation in South Korea will be
      investigated. Furthermore, the outcome will be compared to a South Korean
      counterpart cohort to evaluate the relative health status of NKRs. DISCUSSION:
      The NORNS study targeting adult NKRs in South Korea is a valuable study because
      various scales and medical measurements are employed for the first time. The
      results obtained from this study are expected to be utilized for developing a
      health policy for NKRs and North Korean people after unification. Additionally,
      since NKRs are an immigrant group who are the same race and have the same genetic
      characteristics as South Koreans, this study has the characteristics of a unique
      type of migrant health study.

PMID- 22401815
TI  - Anxiolytic-like actions of reboxetine, venlafaxine and endurance swimming in
      stressed male rats.
AB  - Despite being potent anxiolytic agents, benzodiazepines (BDZ) sometimes show
      reduced therapeutic efficacy in stressed rodents. However, the effectiveness of
      norepinephrine reuptake inhibitors (NRI) and serotonin-norepinephrine reuptake
      inhibitors (SNRI) or other anxiolytic interventions, e.g., exercise, remained
      elusive. Here, we demonstrated that male rats subjected to restraint stress for 4
      weeks showed decreases in percent open arm time and open arm entry, as determined
      by elevated plus-maze test (EPM). Increases in inhibitory avoidance trial 2 and
      outer zone time were also observed in elevated T-maze (ETM) and open field test
      (OFT), respectively. To evaluate the anxiolytic-like actions of exercise and
      anxiolytic drugs, stressed rats were subjected for 4 weeks to swimming or daily
      gavage with 2mg/kg diazepam (BDZ), or 10mg/kg fluoxetine (selective serotonin
      reuptake inhibitor), reboxetine (NRI), or venlafaxine (SNRI). In EPM, the open
      arm activity was higher in the swimming, reboxetine-treated and venlafaxine
      treated groups as compared to age-matched controls, while diazepam and fluoxetine
      were without effect. In ETM, a reduction in avoidance latency was observed only
      in swimming and venlafaxine-treated groups. However, the combined swimming and
      pharmacological treatment showed no additive anxiolytic-like effect. It could be
      concluded that restraint stress induced anxiety-like behaviors, which were not
      responsive to diazepam or fluoxetine, whereas reboxetine, venlafaxine and
      swimming showed anxiolytic-like actions in stressed rats.

PMID- 22401816
TI  - Asymmetrical effect of captopril on the angiotensinase activity in frontal cortex
      and plasma of the spontaneously hypertensive rats: expanding the model of
      neuroendocrine integration.
AB  - There is a reciprocal connection between the frontal cortex (FC) and
      cardiovascular function, and this connection is functionally lateralized. The
      possible pathophysiological impact of neuroendocrine asymmetries is largely
      underestimated. Our aim was to examine the activity of soluble (SOL) and membrane
      bound (MB) aminopeptidases (APs) involved in the renin-angiotensin system in the
      peripheral plasma and in the left and right FC, in both untreated (control) and
      captopril-treated spontaneously hypertensive rats (SHRs). Enzymatic activities
      were measured fluorometrically using arylamide derivatives as substrates.
      Captopril reduced systolic blood pressure, but no differences in plasma AP
      activity were observed between the control and treated SHRs. In contrast, whereas
      the bilateral pattern (left vs. right differences) of SOL activities did not
      substantially change in the FC after captopril treatment, the asymmetries
      observed for MB activities in the FC markedly increased compared with the control
      group. Moreover, correlations between the AP activities in the plasma and those
      in the left or right FC were observed. In the control rats, the plasma AP
      activities correlated significantly with those in the right FC, whereas they
      correlated with those in the left FC in the captopril-treated group. In both
      groups (control and captopril), these correlations were negative for the SOL
      activity but positive for the MB activity. The present results reveal a pattern
      of bilateral behavior between the nervous and cardiovascular systems. The
      inverted bilateral behavior after captopril treatment suggests a systematized,
      lateralized neuroendocrine response representing a regular bilateral behavior
      that has yet to be analyzed.

PMID- 22401817
TI  - Optimally porous and biomechanically compatible scaffolds for large-area bone
      regeneration.
AB  - Large-area or critical-sized bone defects pose a serious challenge in orthopedic
      surgery, as all current treatment options present with shortcomings. Bone tissue
      engineering offers a more promising alternative treatment strategy. However, this
      approach requires mechanically stable scaffolds that support homogenous bone
      formation throughout the scaffold thickness. Despite advances in scaffold
      fabrication, current scaffold-based techniques are unable to support uniform,
      three-dimensional bone regeneration, and are limited to only the scaffold surface
      in vitro and in vivo. This is mainly because of inadequate scaffold pore sizes
      (<200 MUm) and accessible pore volume, and the associated limited oxygen
      diffusion and vascular invasion. In this study, we have adopted a method
      combining microsphere-sintering and porogen-leaching techniques to fabricate
      scaffolds with an increased accessible pore volume. Of the scaffolds developed,
      moderately porous poly(85 lactide-co-15 glycolide) (PLGA) microsphere scaffolds
      were selected as most advantageous, since they retain mechanical strength in the
      range of human cancellous bone and display a significantly higher accessible pore
      volume, which is attributed to an increased percentage of larger pores (i.e.,
      size range 200-600 MUm). Unlike control scaffolds with a limited pore size and an
      accessible pore volume, moderately porous scaffolds displayed increased oxygen
      diffusion, pre-osteoblast cell infiltration, proliferation, and survival
      throughout the entire scaffold. Furthermore, moderately porous PLGA microsphere
      scaffolds displayed enhanced and homogenous mineralization in vitro. Since these
      newly designed moderately porous scaffolds are weight bearing, are fully
      osteoconductive, and have the ability to support vascularization, they may serve
      as effective scaffolds for large-area bone defect repair/regeneration. In
      addition, this study demonstrates the ability to modulate scaffold porosity and,
      in turn, to develop oxygen tension-controlled matrices that are effective for
      large-area bone regeneration.

PMID- 22401818
TI  - Deletion of the Scl +19 enhancer increases the blood stem cell compartment
      without affecting the formation of mature blood lineages.
AB  - The stem cell leukemia (Scl)/Tal1 gene is essential for normal blood and
      endothelial development, and is expressed in hematopoietic stem cells (HSCs),
      progenitors, erythroid, megakaryocytic, and mast cells. The Scl +19 enhancer is
      active in HSCs and progenitor cells, megakaryocytes, and mast cells, but not
      mature erythroid cells. Here we demonstrate that in vivo deletion of the Scl +19
      enhancer (Scl(Delta19/Delta19)) results in viable mice with normal Scl expression
      in mature hematopoietic lineages. By contrast, Scl expression is reduced in the
      stem/progenitor compartment and flow cytometry analysis revealed that the HSC and
      megakaryocyte-erythroid progenitor populations are enlarged in
      Scl(Delta19/Delta19) mice. The increase in HSC numbers contributed to enhanced
      expansion in bone marrow transplantation assays, but did not affect multilineage
      repopulation or stress responses. These results affirm that the Scl +19 enhancer
      plays a key role in the development of hematopoietic stem/progenitor cells, but
      is not necessary for mature hematopoietic lineages. Moreover, active histone
      marks across the Scl locus were significantly reduced in Scl(Delta19/Delta19)
      fetal liver cells without major changes in steady-state messenger RNA levels,
      suggesting post-transcriptional compensation for loss of a regulatory element, a
      result that might be widely relevant given the frequent observation of mild
      phenotypes after deletion of regulatory elements.

PMID- 22401819
TI  - Long-term outcomes associated with pancreatic extracorporeal shock wave
      lithotripsy for chronic calcific pancreatitis.
AB  - BACKGROUND: Most outcomes data on pancreatic extracorporeal shock wave
      lithotripsy (P-ESWL) for chronic calcific pancreatitis (CCP) are based on studies
      with <4 years' follow-up, and U.S. long-term studies are lacking. OBJECTIVE: To
      report long-term P-ESWL outcomes for CCP and to assess whether smoking or alcohol
      use influences P-ESWL outcomes. DESIGN: Cross-sectional study, retrospective
      chart review. SETTING: Virginia Mason Medical Center, Seattle, Washington.
      PATIENTS: This study involved 120 patients who underwent P-ESWL and ERCP for CCP
      and completed an outcomes questionnaire. INTERVENTION: P-ESWL and ERCP, outcomes
      survey. MAIN OUTCOME MEASUREMENTS: Pain, quality of life, narcotics use, diabetes
      status, pancreatic enzyme requirement, repeat P-ESWL, repeat ERCP, surgery.
      RESULTS: A total of 120 patients underwent P-ESWL followed by ERCP (mean +/-
      standard deviation [SD] follow-up 4.3 [+/- 3.7] years) and completed a survey.
      The mean (+/- SD) before-P-ESWL pain score was 7.9 (+/- 2.6) compared with 2.9
      (+/- 2.6) after P-ESWL (P < .001). Improved pain was reported by 102 patients
      (85%); 60 (50%) reported complete pain relief and no narcotic use. The mean (+/-
      SD) before-P-ESWL quality-of-life score was 3.7 (+/- 2.4) compared with 7.3 (+/-
      2.7) after P-ESWL (P < .001). In patients with >= 4 years' follow-up, repeat
      procedures included P-ESWL (29%), ERCP (84%), and surgery (16%). Smokers who quit
      smoking after P-ESWL had improved narcotic requirements compared with those who
      continued smoking (95% vs 67%; P = .014), and a trend suggested a decreased need
      for repeat ERCPs (68% vs 84%; P = .071). LIMITATIONS: Single center,
      retrospective, recall bias, nonvalidated pain and quality-of-life scales.
      CONCLUSION: P-ESWL as the initial therapy for CCP may lead to more lifetime
      procedures; however, partial pain relief in 85%, complete pain relief with no
      narcotic use in 50%, and avoidance of surgery in 84% of patients may be achieved.
      Quitting smoking after P-ESWL may improve outcomes.

PMID- 22401820
TI  - Placement of a covered stent for palliation of a cavitated colon cancer by using
      a novel over-the-scope technique (with video).

PMID- 22401821
TI  - Feasibility of placing a modified fully covered self-expandable metal stent above
      the papilla to minimize stent-induced bile duct injury in patients with
      refractory benign biliary strictures (with videos).
AB  - BACKGROUND: Endoscopic placement of fully covered self-expandable metal stents
      (FCSEMS) has been attempted to manage benign biliary strictures, but currently
      available FCSEMSs may be associated with unintended complications, including de
      novo strictures, in patients with normal life expectancy. OBJECTIVE: To evaluate
      the feasibility of an intraductally placed modified FCSEMS to minimize stent
      induced bile duct injury in patients with benign biliary strictures. DESIGN:
      Prospective observational clinical feasibility study. SETTING: Tertiary-care
      academic center. PATIENTS: This study involved 21 patients with symptomatic
      benign biliary strictures in whom conventional endoscopic management failed.
      INTERVENTION: Strictured segments were 15 mm above the ampulla of Vater. The
      modified FCSEMS has convex margins, a lasso, and an anti-migrating waist on the
      central portion. Stents were placed entirely above the papilla and removed after
      3 to 5 months. MAIN OUTCOME MEASUREMENTS: Success, complications, removability,
      midterm outcome. RESULTS: FCSEMSs were successfully placed inside the bile duct
      in all patients. No episodes of pancreatitis, cholangitis, or sepsis were noted
      during the stenting period. Stent migration occurred in 4 patients (19.0%), but 3
      were asymptomatic during follow-up. All stents were removed successfully with rat
      tooth forceps without complications. Post-stenting cholangiograms showed
      improvement of strictures in 20 of 21 patients, without de novo focal stricture.
      The clinical success rate was 95.2%, with one recurrent stricture. LIMITATIONS:
      The small number and lack of comparison with other types of FCSEMSs. CONCLUSION:
      Temporary intraductal placement of a newly modified FCSEMS effectively improved
      strictures and prevented potential stent-induced complications in patients with
      benign biliary strictures. Controlled large-scale trials are needed to confirm
      the long-term efficacy.

PMID- 22401822
TI  - Gold nanoparticles-decorated silicon nanowires as highly efficient near-infrared
      hyperthermia agents for cancer cells destruction.
AB  - Near-infrared (NIR) hyperthermia agents are of current interest because they hold
      great promise as highly efficacious tools for cancer photothermal therapy.
      Although various agents have been reported, a practical NIR hyperthermia agent is
      yet unavailable. Here, we present the first demonstration that silicon
      nanomaterials-based NIR hyperthermia agent, that is, gold nanoparticles-decorated
      silicon nanowires (AuNPs@SiNWs), is capable of high-efficiency destruction of
      cancer cells. AuNPs@SiNWs are found to possess strong optical absorbance in the
      NIR spectral window, producing sufficient heat under NIR irradiation. AuNPs@SiNWs
      are explored as novel NIR hyperthermia agents for photothermal ablation of tumor
      cells. In particular, three different cancer cells treated with AuNPs@SiNWs were
      completely destructed within 3 min of NIR irradiation, demonstrating the exciting
      potential of AuNPs@SiNWs for NIR hyperthermia agents.

PMID- 22401823
TI  - Endogenous adenosine induces NMDA receptor-independent persistent epileptiform
      discharges in dorsal and ventral hippocampus via activation of A2 receptors.
AB  - Although adenosine is widely assumed to be an endogenous anticonvulsant its role
      in epileptogenesis is still contradictory. Using slices from the dorsal (DH) and
      the vental (VH) rat hippocampus and extracellular recordings from the CA3 field
      we aimed to determine the effects of endogenous adenosine on the expression and
      long-term maintenance of epileptiform activity induced by blockade of adenosine
      receptors types A(1) (A(1)R) and A(2) (A(2)R) under conditions of low magnesium.
      We found that the A(1)Rs blockade induced persistent epileptiform discharges
      (PED) more frequently in VH (by 52%) than in DH (by 31%). The induction of PED
      upon an additional blockade of A(2)Rs increased in VH (by 48%) but decreased in
      DH (by 74%). Remarkably, the increment in VH was prevented by a blockade of
      NMDARs. A blockade of A(2)Rs increased the NMDAR-mediated component of evoked
      synaptic potential in both VH and DH (by ~100%) but suppressed the non-NMDAR
      mediated component in DH but not VH. A blockade of A(1)Rs induced PED equally in
      DH (76%) and VH (80%) via a NMDAR-independent mechanism. A blockade of A(2)Rs
      under blockade of A(1)Rs and NMDARs reduced the PED to 17% in DH and to 38% in
      VH. These findings show that A(2)Rs play a different role in the long-term
      maintenance of epileptiform activity between DH and VH and suggest that
      endogenous activation of A(2)Rs facilitates NMDAR-independent induction of PED in
      both hippocampal poles, but suppresses NMDAR-dependent induction of PED in VH.

PMID- 22401824
TI  - A new species of marine leech (Hirudinida: Piscicolidae) from giant kelpfish,
      Heterostichus rostratus Girard, in southern California.
AB  - Collections of giant kelpfish at inner Cabrillo Beach, San Pedro, California
      revealed the presence of an undescribed species of Heptacyclus, described here as
      Heptacyclus cabrilloi n. sp. The leech is small, only up to 14 mm total length
      including suckers; it has 2 pair of slightly crescentiform eyes on the oral
      sucker, 1 pair of punctiform ocelli on the second annulus of the trachelosome, 13
      pairs of punctiform ocelli dorsally and ventrally on the urosome, and 14 marginal
      punctiform ocelli on the caudal sucker. Pigmentation is yellowish-tan with an
      unpigmented mid-dorsal stripe on both trachelosome and urosome, and with
      unpigmented halos around eyespots and urosome ocelli. Male reproductive system
      with 5 pairs of large, spherical testisacs. Mycetomes present, accessory gland
      cells on atrial cornu absent. Prevalence was 24.1% in June, 2011 with a range of
      1-2 leeches per fish and 25.8% in October, 2011 with a range of 1-6 leeches per
      fish.

PMID- 22401825
TI  - Genome profiling (GP) as an effective tool for monitoring culture collections: a
      case study with Trichosporon.
AB  - Species identification and classification of a large number of microbes are
      essential and heavy workloads in culture collections and relevant laboratories.
      The identification of species usually requires different methods depending on
      species. Therefore, the development of a method which is simple and applicable to
      any organisms will lessen the burdens, increase the reliability of databases and
      thus enhance the science on microbes. The genome profiling (GP) method, developed
      previously, was found effective in monitoring authenticities of all
      strains/species tested in culture collections and expectedly various species,
      which was shown by applying the GP and the conventional sequencing methods to
      identifying and classifying species/strains belonging to the genus Trichosporon
      (38 strains; 16 species). Small differences between strains (11 strains of
      Trichosporon asahii and 4 strains of Trichosporon coremiiforme) can be reliably
      discriminated by GP, which was unsuccessful in the conventional sequencing
      approach. Importantly, seven possible false-assignments contained in the database
      were all pointed out by the GP method with near-perfect correctness, showing the
      power of the GP method.GP was shown to be a potent tool for rapidly and correctly
      monitoring species and strains of fungi in culture collections owing to its
      simple and informative natures.

PMID- 22401826
TI  - ERPs reveal sub-lexical processing in Chinese character recognition.
AB  - The present study used ERPs and a lexical decision task to explore the roles of
      position-general and position-specific radicals and their relative time courses
      in processing Chinese characters. Two types of radical frequency were
      manipulated: the number of characters containing a specific radical irrespective
      of position (i.e., radical frequency or RF) and the number of characters
      containing a specific radical at a particular position (i.e., position-specific
      radical frequency or PRF). The PRF effect was found to be associated with P150,
      P200, and N400, whereas the RF effect was associated with P200. These results
      suggest that both position-general and position-specific radicals could influence
      character processing, but the effect of position-specific radicals appeared
      earlier and lasted longer than that of position-general radicals. These findings
      are interpreted in terms of the specific orthographic properties of the sub
      lexical components of Chinese characters.

PMID- 22401827
TI  - Amygdala response and functional connectivity during emotion regulation: a study
      of 14 depressed adolescents.
AB  - BACKGROUND: Ineffective emotion regulation and abnormal amygdala activation have
      each been found in adolescent-onset major depressive disorder. However, amygdala
      activation during emotion regulation has not been studied in adolescent-onset
      major depressive disorder. METHOD: Fourteen unmedicated adolescents diagnosed
      with current depression without comorbid psychiatric disorders and fourteen well
      matched controls ages 13 to 17 years underwent an emotional regulation task
      during functional magnetic resonance imaging. During this task, participants
      viewed negatively-valence images and were asked to notice how they were feeling
      without trying to change it and maintain their emotional reaction ("Maintain") or
      to interpret the image in such a way as minimize their emotional response
      ("Reduce"). RESULTS: Imaging analyses demonstrated that adolescents with
      depression showed: (1) greater right amygdala activation during the maintain
      condition relative to controls, (2) less connectivity during the maintain
      condition between the amygdala and both the insula and medial prefrontal cortex
      than controls, and (3) a significant positive correlation between amygdala-seeded
      connectivities during maintenance of emotion and psychosocial functioning.
      LIMITATIONS: The current study is a cross-sectional comparison and longitudinal
      investigations with larger sample sizes are needed to examine the association
      between amygdala reactivity and emotion regulation over time in adolescent MDD.
      CONCLUSIONS: During the maintain condition, adolescents with depression showed a
      heightened amygdala response and less reciprocal activation in brain regions that
      may modulate the amygdala. A poorly modulated, overreactive amygdala may
      contribute to poor emotion regulation.

PMID- 22401828
TI  - Pregnancy rates, prenatal and postnatal survival of offspring, and litter sizes
      after reciprocal embryo transfer in DBA/2JHd, C3H/HeNCrl and NMRI mice.
AB  - Success of embryo transfer is often a limiting factor in transgenic procedures
      and rederivation efforts, and depends on the genetic background of the donor and
      recipient strains used. Here we show that embryo transfer to DBA/2J females is
      possible, and present data on pre- and postnatal success rates after reciprocal
      embryo transfer using the inbred DBA/2J and C3H/HeN, and outbred NMRI strains.
      The highest embryo yield was achieved in outbred NMRI females, but embryo yields
      were similar in DBA/2J and C3H/HeN mice following superovulation despite poor
      estrus cycle synchronization in DBA/2J females. In-strain transfer of DBA/2J
      blastocysts (transfer of embryos to recipients from the same strain) resulted in
      pregnancy rates (57.1%) similar to those obtained following in-strain transfer of
      C3H/HeN (60.0%) and NMRI mice (83.3%), although the prenatal survival rate of
      blastocysts was low. Moreover, from the pups born only half survived the
      postnatal period after transfer of DBA/2J and C3H/HeN blastocysts to DBA/2J
      recipients. These problems were not observed when transferring NMRI-blastocysts
      to C3H/HeN and DBA/2J mothers. The number of blastocysts transferred also had a
      positive effect on the success of embryo transfer. In conclusion, C3H/HeN and
      DBA/2J females can be used as recipients for embryo transfer procedures for
      certain donor strains like NMRI, as one major determinant seems to be the genetic
      background of the embryos transferred. We also recommend to increase the number
      of DBA/2J blastocysts transferred, and to foster the DBA/2J pups to other DBA/2J
      mothers postnatally for in-strain transfer of DBA/2J mice.

PMID- 22401829
TI  - Effect of daily semen centrifugation and resuspension on the longevity of equine
      sperm quality following cooled storage.
AB  - An experiment was conducted to determine whether cooled semen quality could be
      maintained for a longer interval by conducting daily centrifugation of extended
      semen, with resuspension of the sperm pellet in fresh extender. Semen treatments
      included SP10NC and SP50NC which contained 10 and 50% seminal plasma,
      respectively, were not centrifuged (NC), and were stored at 4 to 7  degrees C for
      96 h. Treatments SP10C and SP50C contained 10 and 50% seminal plasma,
      respectively, but were centrifuged (C) after 24, 48, and 72 h of cooled storage,
      with daily resuspension in fresh extender containing 10% seminal plasma. Percent
      total sperm motility (TMOT) and progressively motile (PMOT) was reduced (P <
      0.05) in the SP50NC treatment after 24, 48, 72, and 96 h of storage, and TMOT did
      not differ (P > 0.05) in the SP10C, SP50C, SP10NC groups after the same storage
      periods. The % COMP-(alphat) did not differ (P > 0.05) among treatments at any
      time period. Percent membrane intact sperm (SMI) was reduced in SP50NC, as
      compared to SP10C at 48, 72, and 96 h (P < 0.05). Daily centrifugation and
      resuspension of sperm exposed to 50% seminal plasma for the first 24 h (SP50C)
      yielded similar TMOT, PMOT, VCL, SMI, % COMP-(alphat) (P > 0.05) to Groups SP10NC
      and SP10C after 96 h of storage. Daily centrifugation and resuspension of cool
      stored equine semen in fresh extender may be a method to increase sperm
      longevity.

PMID- 22401830
TI  - Testicular ultrasonogram pixel intensity during sexual development and its
      relationship with semen quality, sperm production, and quantitative testicular
      histology in beef bulls.
AB  - This study was conducted to evaluate testicular ultrasonogram pixel intensity
      during sexual development in bulls and to determine its relationship with semen
      quality, sperm production, and quantitative testicular histology. Beef bulls (N =
      152) were examined from 14 - 26 to 70 - 74 wk of age in four different years.
      Testicular echogenicity increased during sexual development, but the pattern of
      change differed among years. Echogenicity increased between 26 and 42 to 46 wk of
      age in 2 yr, but increased considerably earlier in the other 2 yr, reaching
      maximum values at 34 wk of age. Because increased echogenicity was likely
      associated with testicular changes leading to initiation of spermatogenesis,
      these differences were difficult to explain considering that age at puberty did
      not differ significantly among years. When data were evaluated according to age
      normalized to puberty, echogenicity started to increase 16 to 12 wk before
      puberty and reached maximum values 4 wk before or at puberty. These results
      indicate that a certain developmental stage of the testicular parenchyma must be
      reached before puberty and that the composition of the parenchyma remained
      consistent after puberty. Testicular echogenicity was associated with sperm
      production, seminiferous tubule and epithelium area, and sperm morphology, but
      the associations were not consistent. Testicular echogenicity was a good
      indicator of pubertal and mature status, but was not superior to scrotal
      circumference. In conclusion, although testicular ultrasonogram pixel intensity
      analysis might be useful for research purposes, clinical application of this
      technology in the present form for bull breeding soundness evaluation is not
      justifiable.

PMID- 22401831
TI  - In vitro optimization of the Gallus domesticus oviduct epithelial cells culture.
AB  - The aim of this experiment was to establish an efficient method for isolation and
      further culture in vitro of the normal chicken oviduct epithelial cells (COEC)
      for cell-based research models. Different factors were tested to optimize COEC
      primary culture for repeatable results: the origin of isolated cells (oviduct
      Infundibulum or Magnum section); the oviduct tissue dissociation procedure
      (mechanical scrapping or mincing), tissue digestion times (15, 30 and 45 min),
      the culture plates coating (colagene I, polystyrene surface or 3T3 feeder layer),
      the growth media (classic DMEM/Ham's F12 and defined serum-free medium, Lonza
      Switzerland), incubation temperature (37  degrees C vs 41 degrees C) and
      different cell seeding numbers: 0.2M, 0.5M and 1.0M cells/well. The COEC isolated
      by mincing the Infundibular neck and digestion of tissue for 30 min formed cell
      aggregates of bright colour and gave proliferating colonies of epithelial-like
      character which was the best result obtained from all applied procedures in our
      studies. The fibroblast-like cells considered as contaminants occurred only
      sporadically up to day 7 of culture. Seeding about 1M cells in 1 mL of serum-free
      medium onto 12-well dishes gave the optimal growth of colonies resulting in 5 to
      7 confluent culture wells from a single oviduct sample. Feeder layer and collagen
      I did not improve adhesion of the COEC to the culture vessel. Adoption of 37 
      degrees C and 41  degrees C did not reveal apparent differences to the condition
      of cultured COEC. Cell differentiation and proliferation potential depends on
      number and replicative capacity of isolated progenitors. The progenitors are
      responsible for holoclones formation and good culture growth. The percentage of
      colonies developed from the cells isolated from Infundibulum was greater than
      that of other samples in our studies. We conclude that the model of COEC primary
      cultures from different segments of oviduct, in particular infundibulum, should
      be incorporated to the range of avian cells research as this work generates
      questions about undocumented sources of oviduct progenitor cells.

PMID- 22401832
TI  - The effect of equine chorionic gonadotropin (eCG) on pregnancy rates of white
      tailed deer following fixed-timed artificial insemination.
AB  - Control of the white-tailed doe's reproductive cycle is not well documented. The
      objective was to determine the effects of giving equine chorionic gonadotropin
      (eCG) at progesterone device removal on fixed time artificial insemination (FTAI)
      pregnancy rates in white-tailed does. All does (n = 74) were synchronized with a
      vaginal progesterone implant (CIDR; 0.3 g progesterone), inserted on Day 0
      (without regard to stage of estrous cycle), removed 14 days later, and subjected
      to FTAI, on average, 60 h post-CIDR removal. Of these, 34 were given 200 IU (im)
      of eCG at CIDR removal. Overall, FTAI pregnancy rate was 50% across 2 yrs (effect
      of year, P = 0.35). Administration of eCG at CIDR removal did not affect (P =
      0.16) pregnancy rate (eCG = 59%; no eCG = 43%). Pregnancy rates were not affected
      by vulva score or doe disposition. Does that were <= 4 yrs old were more likely
      (P = 0.01) to become pregnant than does > 4 yrs of age. Does inseminated >= 60.5
      h after CIDR removal were 22 times more likely (P = 0.002) to become pregnant to
      FTAI than does inseminated < 60.5 h. When frozen-thawed semen was deposited in
      the cervix or uterus, does were 17 times more likely (P = 0.005) to become
      pregnant compared with those receiving intravaginal insemination. Fecundity was
      not different (P = 0.73) across treatment groups (1.6 +/- 0.11; no eCG vs. 1.7 +/
      0.10; eCG). Furthermore, fecundity of does pregnant to FTAI was not different (P
      = 0.72) compared with does pregnant to clean-up bucks (1.7 +/- 0.08; AI does vs.
      1.7 +/- 0.09; clean-up bucks). In summary, white-tailed does were successfully
      inseminated using a 14 days FTAI protocol, eCG may not be essential for
      acceptable pregnancy rates, and increased pregnancy rates may result when FTAI is
      done >= 60.5 h after progesterone device removal.

PMID- 22401833
TI  - Ovarian estradiol modulates the stimulatory effect of ovulation-inducing factor
      (OIF) on pituitary LH secretion in llamas.
AB  - This study was designed to: 1) characterize the effect of ovulation-inducing
      factor (OIF) on pituitary LH secretion in ovariectomized (OVX) llamas; and 2)
      determine the effect of OIF on LH secretion in OVX llamas pretreated with
      estradiol-17beta (E-17beta) or estradiol benzoate (EB). In Experiment 1, intact
      and OVX llamas (n = 5 or 6 per group) were assigned to a two by two factorial
      design: 1) Intact llamas treated with 1 mL of phosphate buffered saline (PBS); 2)
      Intact llamas treated with 1 mg of purified OIF; 3) OVX llamas treated with 1 mL
      of PBS; or 4) OVX llamas treated with 1 mg of purified OIF. In Experiment 2,
      intact and OVX llamas (n = 5 or 6 per group) were randomly assigned to the
      following groups: 1) Intact llamas treated with 1 mg of purified OIF; 2) OVX
      llamas treated with 1.0 mL of PBS; 3) OVX llamas treated with 1.0 mg of purified
      OIF; 4) OVX llamas primed with E-17beta, followed by 1.0 mg of purified OIF.
      Experiment 3 was similar as described for Experiment 2, except that priming was
      done with EB. In Experiment 1, animal category by treatment and animal category
      by treatment by time interactions tended (P = 0.08) to affect LH concentration.
      The effect of OIF on LH released was partly restored (P < 0.05), to the values
      observed for the intact OIF-treated females, when OVX llamas were primed with E
      17beta or BE (Experiments 2 and 3). We concluded that peripheral estradiol
      concentrations in llamas partially modulates the effect of OIF on pituitary LH
      secretion; however, other ovarian factor(s) could also participate in this
      modulatory action.

PMID- 22401834
TI  - Superovulation of beef cattle with a split-single intramuscular administration of
      Folltropin-V in two concentrations of hyaluronan.
AB  - Three experiments were designed to evaluate the superovulatory response of beef
      cows following two intramuscular (IM) administrations 48 h apart of Folltropin-V
      diluted in reduced concentrations of hyaluronan (Split-single IM administrations;
      Experiment 1-300 mg Folltropin-V on the first day and 100 mg 48 h later;
      Experiment 2-200 mg Folltropin-V on the first day and 100 mg 48 h later). In
      Experiments 1 and 2, superovulatory response and ova embryo/embryo production did
      not differ between donors receiving twice daily IM of Folltropin-V over 4 days
      and those given a Split-single IM administration of Folltropin-V diluted in 10
      mg/mL hyaluronan solution. Experiment 3 compared Split-single IM administration
      of Folltropin-V diluted in two hyaluronan concentrations (5 or 10 mg/mL) with
      Folltropin-V diluted in saline and administered twice-daily over 4 days. Beef
      cows (17 Angus and 12 Simmental) were randomly assigned to one of three treatment
      groups to be superstimulated three times in a cross-over design, so that all cows
      received all treatments. A total dose of 300 mg Folltropin-V was divided into
      twice-daily IM over 4 days, or in two IM treatment 48 h apart (200 mg on first
      day and 100 mg 48 h later) in the hyaluronan groups. Mean (+/- SEM) numbers of
      transferable embryos did not differ among treatment groups (Control: 4.0 +/- 0.8;
      10 mg/mL hylauronan: 5.0 +/- 0.9; 5 mg/mL hyaluronan: 6.1 +/- 1.3). We concluded
      that the Split-single IM administration of Folltropin-V diluted in either
      concentration of hyaluronan resulted in a comparable superovulatory response to
      the traditional twice-daily protocol.

PMID- 22401835
TI  - Analysis of in vivo oocyte maturation, in vitro embryo development and gene
      expression in cumulus cells of dairy cows and heifers selected for one fertility
      quantitative trait loci (QTL) located on BTA3.
AB  - We have previously shown that Holstein cows selected for their homozygous
      favorable ("fertil+") or unfavorable ("fertil-") haplotype at one quantitative
      trait loci (QTL) of female fertility located on chromosome 3 (QTL-F-Fert-BTA3)
      had a different success rate 35 and 90 days after the first artificial
      insemination. To determine whether the lower fertility in "fertil-" animals could
      be related to oocyte quality, we analyzed the embryo development rate in vitro
      and the oocyte meiotic maturation in vivo in "fertil+" and "fertil-" heifers. In
      vitro maturation and fertilization of immature oocytes recovered by ovum pick-up
      from "fertil+" and "fertil-" heifers resulted in similar cleavage and blastocyst
      rates in the two haplotypes. However the percentage of expanded blastocysts and
      the number of cells per blastocyst were significantly higher in "fertil+".
      Oocytes from presumptive preovulatory follicles were analyzed after ovarian
      stimulation. A similar rate of immature (from prophase to metaphase-I) and mature
      oocytes (metaphase-II) was obtained in the two haplotypes, whereas a
      significantly higher percentage of oocytes from metaphase-I to metaphase-II was
      observed in "fertil+" compared to "fertil-" heifers. Since cumulus cells (CCs)
      could reflect the developmental competence of oocytes, we analyzed the expression
      of seven genes included in the QTL-F-Fert-BTA3 using real-time PCR in bovine CCs
      after in vivo or in vitro maturation, as a model of higher and lower competence,
      respectively. Transcript levels of TAGLN2, EEF1A1 and PIGM were higher in CCs
      after in vitro maturation (IVM) compared to in vivo maturation, whereas no
      difference was observed for IFI16, KIRREL, SPTA1 and PEX19 expression. The
      expression levels of all these genes in in preovulatory CCs were not
      significantly different between "fertil+" and "fertil-" heifers. In conclusion,
      the lower fertility of "fertil-" females could be partially due to a lowest
      quality of the oocytes and consequently of preimplantation embryo development.

PMID- 22401836
TI  - Apoptosis-mediated seasonal testicular regression in the Japanese Jungle Crow
      (Corvus macrorhynchos).
AB  - The present study investigated effects of apoptosis observed during seasonal
      testicular regression in Japanese Jungle Crows. The study was conducted during
      January to June 2008, 2009. Testes from adults captured during non-breeding
      (January), prebreeding (February to mid-March), main-breeding (late March to
      early May), transition (mid-May to late May), and post-breeding (June) seasons
      were analyzed. Apoptosis was assessed by in situ terminal deoxynucleotidyl
      transferase-mediated dUTP nick end-labeling (TUNEL) assay. Paired-testis volume
      increased 95-fold from the non-breeding to the main-breeding season (P < 0.05),
      and subsequently decreased 26-fold from the main breeding to the post-breeding
      season (P < 0.05). Testicular activity was evaluated from the total germ cell
      count and sperm index, which increased 42- and 5-fold, respectively, in the main
      breeding season, and subsequently decreased 33- and 5-fold in the post-breeding
      season. In testes, TUNEL-positive germ cells were at low levels in the non
      breeding season, absent in the prebreeding and the main-breeding seasons, and
      highest in mid-May (P < 0.05). In contrast, TUNEL-positive Sertoli cells occurred
      only in late-April. In addition, TUNEL-positive fibroblast-like cells were
      observed in the outer zone of the tunica albuginea in the post-breeding season.
      Collectively, these data suggested that the seasonal rise in the testicular
      competence occurred slowly in Japanese Jungle Crows; however, testis function was
      terminated rapidly after the breeding season. Furthermore, we concluded, similar
      to other avian species, Sertoli cell apoptosis followed by massive germ cell
      death was responsible for rapid testicular regression in Jungle Crows.

PMID- 22401837
TI  - Medical and developmental risk factors of catatonia in children and adolescents:
      a prospective case-control study.
AB  - CONTEXT: Rare diseases have been associated with more and more genetic and non
      genetic causes and risk factors. But this has not been systematically assessed in
      catatonia, one of the psychiatric syndromes, that is most frequently associated
      with medical condition. OBJECTIVE: We sought to assess the medical and
      developmental risk factors of catatonia in children and adolescents. METHODS:
      From 1993 to 2009, 58 youths aged 10 to 18 years were prospectively admitted for
      catatonia and were followed up after discharge. A multidisciplinary approach
      assessed patients' medical condition and developmental history. A causality
      assessment scored medical risk (maximum score=10; kappa=0.91). We compared the
      prevalence of catatonia in these patients to that of 80 inpatients with bipolar I
      disorder admitted from 1993 to 2003 who were also followed up. RESULTS: We found
      that 13 (22.4%) patients had medical conditions and 18 (31%) had a history of
      developmental disorder in the catatonia group, whereas 1 (1.3%) and 17 (22.6%)
      patients had the same conditions in the bipolar group (p<0.001; p=0.17,
      respectively). Medical conditions associated with catatonia included auto-immune
      encephalitis (systemic lupus erythematosus [N=3] and anti-NMDA-receptor
      encephalitis [N=1]), seizures (N=1), ciclosporin encephalitis (N=1), post
      hypoglycaemic coma encephalitis (N=1), and genetic or metabolic conditions
      (chorea [N=2], 5HT cerebrospinal fluid deficit [N=1], storage disease [N=1],
      fatal familial insomnia [FFI; N=1], and PRODH mutations [N=1]). Six patients
      responded to a specific treatment approach related to their medical condition
      (e.g., plasma exchange in the case of auto-immune encephalitis). CONCLUSION:
      Catatonia in children and adolescents is associated with a high prevalence of
      medical conditions. This needs to be acknowledged as it may greatly delay the
      treatment of catatonia and the diagnosis of medically related catatonia.
      Tragically, this may deny patients treatment opportunities.

PMID- 22401838
TI  - DNA-controlled excitonic switches.
AB  - Fluorescence resonance energy transfer (FRET) is a promising means of enabling
      information processing in nanoscale devices, but dynamic control over exciton
      pathways is required. Here, we demonstrate the operation of two complementary
      switches consisting of diffusive FRET transmission lines in which exciton flow is
      controlled by DNA. Repeatable switching is accomplished by the removal or
      addition of fluorophores through toehold-mediated strand invasion. In principle,
      these switches can be networked to implement any Boolean function.

PMID- 22401839
TI  - Characterization of ionic channels underlying the specific firing pattern of a
      novel neuronal subtype in the rat prepositus hypoglossi nucleus.
AB  - In our previous study on the prepositus hypoglossi nucleus (PHN), we found a
      neuronal subtype exhibiting a specific firing pattern in which the first
      interspike interval (ISI) was longer than that of the second, designated FIL
      (first interspike interval long) neurons. In the present study, we explored the
      ionic mechanisms underlying this firing pattern using whole-cell recordings of
      rat brainstem slice preparations. In addition to a longer first ISI, FIL neurons
      showed properties such as increased slow afterhyperpolarization (AHP) of the
      first spike relative to the second spike. The application of 4-aminopyridine (4
      AP) shortened the longer first ISI and reduced the larger AHP of the first spike,
      but alpha-dendrotoxin affected neither the ISI nor the AHP. A voltage clamp study
      revealed that FIL neurons express transient outward currents with slow decay
      kinetics. When T-type Ca(2+) currents alone or T-type Ca(2+) plus persistent
      Na(+) currents were blocked, the FIL firing pattern changed to one with transient
      hyperpolarization and delayed spike generation characteristic of late-spiking
      neurons. These findings indicate that A-type K(+) currents showing slow decay, T
      type Ca(2+) currents, and persistent Na(+) currents all contribute to the
      specific firing pattern of FIL neurons.

PMID- 22401840
TI  - Ca2+-dependent regulation of synaptic vesicle endocytosis.
AB  - Action potentials, when arriving at presynaptic terminals, elicit Ca(2+) influx
      through voltage-gated Ca(2+) channels. Intracellular [Ca(2+)] elevation around
      the channels subsequently triggers synaptic vesicle exocytosis and also induces
      various protein reactions that regulate vesicle endocytosis and recycling to
      provide for long-term sustainability of synaptic transmission. Recent studies
      using membrane capacitance measurements, as well as high-resolution optical
      imaging, have revealed that the dominant type of synaptic vesicle endocytosis at
      central nervous system synapses is mediated by clathrin and dynamin. Furthermore,
      Ca(2+)-dependent mechanisms regulating endocytosis may operate in different ways
      depending on the distance from Ca(2+) channels: (1) intracellular Ca(2+) in the
      immediate vicinity of a Ca(2+) channel plays an essential role in triggering
      endocytosis, and (2) intracellular Ca(2+) traveling far from the channels has a
      modulatory effect on endocytosis at the periactive zone. Here, I integrate the
      latest progress in this field to propose a compartmental model for regulation of
      vesicle endocytosis at synapses and discuss the possible roles of presynaptic
      Ca(2+)-binding proteins including calmodulin, calcineurin and synaptotagmin.

PMID- 22401841
TI  - Challenges in developing medicinal plant databases for sharing
      ethnopharmacological knowledge.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Major research contributions in ethnopharmacology
      have generated vast amount of data associated with medicinal plants. Computerized
      databases facilitate data management and analysis making coherent information
      available to researchers, planners and other users. Web-based databases also
      facilitate knowledge transmission and feed the circle of information exchange
      between the ethnopharmacological studies and public audience. However, despite
      the development of many medicinal plant databases, a lack of uniformity is still
      discernible. Therefore, it calls for defining a common standard to achieve the
      common objectives of ethnopharmacology. AIM OF THE STUDY: The aim of the study is
      to review the diversity of approaches in storing ethnopharmacological information
      in databases and to provide some minimal standards for these databases. MATERIALS
      AND METHODS: Survey for articles on medicinal plant databases was done on the
      Internet by using selective keywords. Grey literatures and printed materials were
      also searched for information. Listed resources were critically analyzed for
      their approaches in content type, focus area and software technology. RESULTS:
      Necessity for rapid incorporation of traditional knowledge by compiling primary
      data has been felt. While citation collection is common approach for information
      compilation, it could not fully assimilate local literatures which reflect
      traditional knowledge. Need for defining standards for systematic evaluation,
      checking quality and authenticity of the data is felt. Databases focussing on
      thematic areas, viz., traditional medicine system, regional aspect, disease and
      phytochemical information are analyzed. Issues pertaining to data standard, data
      linking and unique identification need to be addressed in addition to general
      issues like lack of update and sustainability. In the background of the present
      study, suggestions have been made on some minimum standards for development of
      medicinal plant database. CONCLUSION: In spite of variations in approaches,
      existence of many overlapping features indicates redundancy of resources and
      efforts. As the development of global data in a single database may not be
      possible in view of the culture-specific differences, efforts can be given to
      specific regional areas. Existing scenario calls for collaborative approach for
      defining a common standard in medicinal plant database for knowledge sharing and
      scientific advancement.

PMID- 22401843
TI  - Focus on methodology: salivary bioscience and research on adolescence: an
      integrated perspective.
AB  - The characterization of the salivary proteome and advances in biotechnology
      create an opportunity for developmental scientists to measure multi-level
      components of biological systems in oral fluids and identify relationships with
      developmental processes and behavioral and social forces. The implications for
      developmental science are profound because from a single oral fluid specimen,
      information can be obtained about a broad array of biological systems and the
      genetic polymorphisms related to their function. The purpose of this review is to
      provide a conceptual and tactical roadmap for investigators interested in
      integrating these measurement tools into research on adolescent health and
      development.

PMID- 22401842
TI  - Sexual minority status, peer harassment, and adolescent depression.
AB  - The well-documented higher rates of depression among sexual minority youth are
      increasingly viewed by developmentalists as a byproduct of the stigmatization of
      sexual minority status in American society and of the negative impact this stigma
      has on the processes associated with depression. This study attempted to spur
      future research by testing Hatzenbuehler's (2009) psychological mediation
      framework to investigate the ways in which peer harassment related to sexuality
      puts young people at risk by influencing the cognitive, social, and regulatory
      factors associated with depression. Analyses of 15 year olds in the NICHD Study
      of Early Child Care and Youth Development revealed that sexual minority status
      was largely associated with depressive outcomes via harassment, which was
      subsequently associated with depression via cognitive and social factors. Results
      point to various avenues for exploring the importance of the social world and
      self-concept for the outcomes of sexual minority adolescents in the future.

PMID- 22401844
TI  - Hormonal regulation of root growth: integrating local activities into global
      behaviour.
AB  - To date, plant researchers have probed the control of root growth by studying the
      roles of individual regulatory components or cellular processes. However, recent
      studies in the Arabidopsis (Arabidopsis thaliana) root have shown that different
      hormones control organ growth by regulating specific growth processes (cell
      proliferation, differentiation or expansion) in distinct tissues. We discuss key
      issues raised by these new insights and hypothesise that novel tissue-to-tissue
      signals exist to coordinate organ growth. We conclude by describing how
      multiscale models can help probe the interplay between the different scales at
      which hormones and their regulatory networks operate in different cells and
      tissues. Such approaches promise to generate new insights into the mechanisms
      that control root growth.

PMID- 22401845
TI  - Leaf size control: complex coordination of cell division and expansion.
AB  - Size control of multicellular organisms poses a longstanding biological question
      that has always fascinated scientists. Currently the question is far from being
      resolved because of the complexity of and interconnection between cell division
      and cell expansion, two different events necessary to form a mature organ.
      Because of the importance of plants for food and renewable energy sources,
      dissecting the genetic networks underlying plant growth and organ size is
      becoming a high priority in plant science worldwide. Here, we review the current
      understanding of the cellular and molecular mechanisms that govern leaf organ
      size and discuss future prospects on research aiming at understanding organ size
      regulation.

PMID- 22401846
TI  - Infection of capilloviruses requires subgenomic RNAs whose transcription is
      controlled by promoter-like sequences conserved among flexiviruses.
AB  - The first open-reading frame (ORF) of apple stem grooving virus (ASGV), of the
      genus Capillovirus, encodes an apparently chimeric polyprotein containing
      conserved regions for replicase (Rep) and coat protein (CP). However, our
      previous study revealed that ASGV mutants with distinct and discontinuous Rep-
      and CP-coding regions successfully infect plants, indicating that CP expressed
      via a subgenomic RNA (sgRNA) is sufficient for viability of the virus. Here we
      identified a transcription start site of the CP sgRNA and revealed that CP
      translated from the sgRNA is essential for ASGV infection. We mapped the
      transcription start sites of both the CP and the movement protein (MP) sgRNAs of
      ASGV and found a hexanucleotide motif, UUAGGU, conserved upstream from both sgRNA
      transcription start sites. Mutational analysis of the putative CP initiation
      codon and of the UUAGGU sequence upstream from the transcription start site of CP
      sgRNA demonstrated their importance for ASGV accumulation. Our results also
      demonstrated that potato virus T (PVT), an unassigned species closely related to
      ASGV, produces two sgRNAs putatively deployed for the CP and MP expression and
      that the same hexanucleotide motif as found in ASGV is located upstream from the
      transcription start sites of both sgRNAs. This motif, which constituted putative
      core elements of the sgRNA promoter, is broadly conserved among viruses in the
      families Alphaflexiviridae and Betaflexiviridae, suggesting that the gene
      expression strategy of the viruses in both families has been conserved throughout
      evolution.

PMID- 22401847
TI  - Complete genomic sequence and taxonomic position of eel virus European X (EVEX),
      a rhabdovirus of European eel.
AB  - Eel virus European X (EVEX) was first isolated from diseased European eel
      Anguilla anguilla in Japan at the end of seventies. The virus was tentatively
      classified into the Rhabdoviridae family on the basis of morphology and
      serological cross reactivity. This family of viruses is organized into six genera
      and currently comprises approximately 200 members, many of which are still
      unassigned because of the lack of molecular data. This work presents the
      morphological, biochemical and genetic characterizations of EVEX, and proposes a
      taxonomic classification for this virus. We provide its complete genome sequence,
      plus a comprehensive sequence comparison between isolates from different
      geographical origins. The genome encodes the five classical structural proteins
      plus an overlapping open reading frame in the phosphoprotein gene, coding for a
      putative C protein. Phylogenic relationship with other rhabdoviruses indicates
      that EVEX is most closely related to the Vesiculovirus genus and shares the
      highest identity with trout rhabdovirus 903/87.

PMID- 22401848
TI  - Patterns of variation of intertidal species of commercial interest in the Parque
      Litoral Norte (north Portugal) MPA: comparison with three reference shores.
AB  - Marine Protected Areas (MPAs) are world-wide established with the aim of
      conserving biodiversity and preventing overexploitation of marine organisms.
      Evaluating the effectiveness of MPAs is needed in order to support and implement
      their management, but it is complicated by the large natural variability in space
      and time of distribution and abundance of natural populations. Here, we tested
      the hypothesis that patterns of total abundance and size-frequency distribution
      of two intensively harvested intertidal species (the sea urchin Paracentrotus
      lividus and the mussel Mytilus galloprovincialis) differed between a protected
      and three reference shores along the rocky coast of north Portugal. Response
      variables were in terms of mean values and measures of variance at different
      spatial scales (from centimetres to metres) and over time (along a period of
      about 12 months). A further comparison involved the estimation of the
      reproductive potential of sea urchins, quantified as variations of Gonad Index
      (GI = gonad dry weight/body dry weight * 100) at the scale of shore. Results did
      not generally support a predictable direct effect of protection, as the total
      abundance and the abundance of larger individuals of both species and GI did not
      differ between the MPA and reference shores. However, a considerable temporal and
      spatial variability at smaller scales was detected for several response
      variables. Such findings have implications for management of MPAs, highlighting
      the need for sampling designs properly replicated in space and time, in order to
      examine their effectiveness, and for considering spatial and temporal
      heterogeneity of target populations and driving processes as a criterion for
      their implementation and design.

PMID- 22401849
TI  - Reproductive effects in F1 adult females exposed in utero to moderate to high
      doses of mono-2-ethylhexylphthalate (MEHP).
AB  - Phthalates are widely used as plasticizers in everyday products. Yet, studies on
      the effects of phthalates on female reproductive health are limited. In this
      study, pregnant C57/Bl6 mice were exposed via oral gavage to corn oil, 100, 500,
      or 1000mg/kg MEHP from gestational days 17-19. Reproductive lifespan was
      decreased by one month in the highest F1 exposure group (9.8+/-0.4 versus 11.1+/
      0.6 months in control F1 females). F1 females exhibited delayed estrous onset at
      the two higher exposures and prolonged estrus was observed in all MEHP-exposed
      females. Serum FSH and estradiol were significantly elevated at the highest
      exposure and altered mRNA expression was found for the steroidogenic genes LHCGR,
      aromatase, and StAR. At one year of age, mammary gland hyperplasia was observed
      in high dose MEHP-exposed females. In summary, late gestational exposure to MEHP
      leads to multiple latent reproductive effects throughout murine life resulting in
      premature ovarian senescence and mammary hyperplasia.

PMID- 22401850
TI  - Heterodichogamy in Kingdonia (Circaeasteraceae, Ranunculales).
AB  - BACKGROUND AND AIMS: Preliminary field observations in 2001 and 2002 suggested
      that Kingdonia uniflora (Circaeasteraceae, Ranunculales) exhibits
      heterodichogamy, an unusual kind of reproductive heteromorphy, hitherto
      unreported in Ranunculales and known from only one other genus in basal eudicots.
      METHODS: During several subsequent years flowers were observed in the field.
      Flowers were fixed in FAA and studied with microtome sections series and with the
      scanning electron microscope. KEY RESULTS: The flowers proved to be
      heterodichogamous, with protandrous and protogynous morphs, which have a 1 : 1
      ratio. Both morphs equally set fruit. Each year a single flower is formed at the
      tip of a rhizome or more rarely two flowers. The flowers are already open when
      they appear at the soil surface, before they are receptive and before pollen is
      dispersed. In both floral morphs the styles elongate early and the stigmas are
      positioned above the anthers before anthesis begins. In protogynous flowers the
      stigmas become receptive in this position; later the styles become reflexed and
      then the anthers dehisce. In contrast, in protandrous flowers the stamen
      filaments elongate during early anthesis such that the dehiscing anthers come to
      lie above the (still unreceptive) stigmas; after dehiscence of all anthers in a
      flower the styles begin to elongate and become receptive. CONCLUSIONS: This is
      the first record of heterodichogamy in a representative of Ranunculales, in an
      herbaceous eudicot, and in a plant with uniflorous ramets. The occurrence of
      heterodichogamy in Kingdonia in which clonal reproduction appears to be dominant
      might be an adaptation to avoid mating between the ramets from a common mother
      individual (genet).

PMID- 22401851
TI  - Ribosomal production and in vitro selection of natural product-like
      peptidomimetics: the FIT and RaPID systems.
AB  - Bioactive natural product peptides have diverse architectures such as non
      standard sidechains and a macrocyclic backbone bearing modifications. In vitro
      translation of peptides bearing these features would provide the research
      community with a diverse collection of natural product peptide-like molecules
      with a potential for drug development. The ordinary in vitro translation system,
      however, is not amenable to the incorporation of non-proteinogenic amino acids or
      genetic encoding of macrocyclic backbones. To circumvent this problem, flexible
      tRNA-acylation ribozymes (flexizymes) were combined with a custom-made
      reconstituted translation system to produce the flexible in vitro translation
      (FIT) system. The FIT system was integrated with mRNA display to devise an in
      vitro selection technique, referred to as the random non-standard peptide
      integrated discovery (RaPID) system. It has recently yielded an N-methylated
      macrocyclic peptide having high affinity (Kd=0.60 nM) for its target protein,
      E6AP.

PMID- 22401852
TI  - Molecular mechanism of force induced stabilization of collagen against enzymatic
      breakdown.
AB  - Collagen cleavage, facilitated by collagenases of the matrix metalloproteinase
      (MMP) family, is crucial for many physiological and pathological processes such
      as wound healing, tissue remodeling, cancer invasion and organ morphogenesis.
      Earlier work has shown that mechanical force alters the cleavage rate of
      collagen. However, experimental results yielded conflicting data on whether
      applying force accelerates or slows down the degradation rate. Here we explain
      these discrepancies and propose a molecular mechanism by which mechanical force
      might change the rate of collagen cleavage. We find that a type I collagen
      heterotrimer is unfolded in its equilibrium state and loses its triple helical
      structure at the cleavage site without applied force, possibly enhancing
      enzymatic breakdown as each chain is exposed and can directly undergo hydrolysis.
      Under application of force, the naturally unfolded region refolds into a triple
      helical structure, potentially protecting the molecule against enzymatic
      breakdown. In contrast, a type I collagen homotrimer retains a triple helical
      structure even without applied force, making it more resistant to enzyme
      cleavage. In the case of the homotrimer, the application of force may directly
      lead to molecular unwinding, resulting in a destabilization of the molecule under
      increased mechanical loading. Our study explains the molecular mechanism by which
      force may regulate the formation and breakdown of collagenous tissue.

PMID- 22401853
TI  - Protein disulfide isomerase in redox cell signaling and homeostasis.
AB  - Thiol proteins may potentially act as redox signaling adaptor proteins, adjusting
      reactive oxygen species intermediates to specific signals and redox signals to
      cell homeostasis. In this review, we discuss redox effects of protein disulfide
      isomerase (PDI), a thioredoxin superfamily oxidoreductase from the endoplasmic
      reticulum (ER). Abundantly expressed PDI displays ubiquity, interactions with
      redox and nonredox proteins, versatile effects, and several posttranslational
      modifications. The PDI family contains >20 members with at least some apparent
      complementary actions. PDI has oxidoreductase, isomerase, and chaperone effects,
      the last not directly dependent on its thiols. PDI is a converging hub for
      pathways of disulfide bond introduction into ER-processed proteins, via hydrogen
      peroxide-generating mechanisms involving the oxidase Ero1alpha, as well as
      hydrogen peroxide-consuming reactions involving peroxiredoxin IV and the novel
      peroxidases Gpx7/8. PDI is a candidate pathway for coupling ER stress to oxidant
      generation. Emerging information suggests a convergence between PDI and Nox
      family NADPH oxidases. PDI silencing prevents Nox responses to angiotensin II and
      inhibits Akt phosphorylation in vascular cells and parasite phagocytosis in
      macrophages. PDI overexpression spontaneously enhances Nox activation and
      expression. In neutrophils, PDI redox-dependently associates with p47phox and
      supports the respiratory burst. At the cell surface, PDI exerts transnitrosation,
      thiol reductase, and apparent isomerase activities toward targets including
      adhesion and matrix proteins and proteases. Such effects mediate redox-dependent
      adhesion, coagulation/thrombosis, immune functions, and virus internalization.
      The route of PDI externalization remains elusive. Such multiple redox effects of
      PDI may contribute to its conspicuous expression and functional role in disease,
      rendering PDI family members putative redox cell signaling adaptors.

PMID- 22401854
TI  - Mitochondrial superoxide production contributes to vancomycin-induced renal
      tubular cell apoptosis.
AB  - Vancomycin chloride (VCM), a glycopeptide antibiotic, is widely used for the
      therapy of infections caused by methicillin-resistant Staphylococcus aureus.
      However, nephrotoxicity is a major adverse effect in VCM therapy. In this study,
      we investigated the cellular mechanisms underlying VCM-induced renal tubular cell
      injury in cultured LLC-PK1 cells. VCM induced a concentration- and time-dependent
      cell injury in LLC-PK1 cells. VCM caused increases in the numbers of annexin V
      positive/PI-negative cells and TUNEL-positive cells, indicating the involvement
      of apoptotic cell death in VCM-induced renal cell injury. The VCM-induced
      apoptosis was accompanied by the activation of caspase-9 and caspase-3/7 and
      reversed by inhibitors of these caspases. Moreover, VCM caused an increase in
      intracellular reactive oxygen species production and mitochondrial membrane
      depolarization, which were reversed by vitamin E. In addition, mitochondrial
      complex I activity was inhibited by VCM as well as by the complex I inhibitor
      rotenone, and rotenone mimicked the VCM-induced LLC-PK1 cell injury. These
      findings suggest that VCM causes apoptotic cell death in LLC-PK1 cells by
      enhancing mitochondrial superoxide production leading to mitochondrial membrane
      depolarization followed by the caspase activities. Moreover, mitochondrial
      complex I may play an important role in superoxide production and renal tubular
      cell apoptosis induced by VCM.

PMID- 22401855
TI  - Microphthalmia-associated transcription factor modulates expression of NADPH
      oxidase type 4: a negative regulator of melanogenesis.
AB  - How signaling via reactive oxygen species (ROS) influences skin pigmentation is
      unclear. We have investigated how NADPH oxidase-derived ROS modulates the
      expression of the key pigment "melanin" synthesizing enzymes in B16 mouse
      melanoma cells. A melanin inducer alpha-melanocyte-stimulating hormone (alpha
      MSH) caused ROS generation that was inhibited by the NADPH oxidase inhibitor
      Diphenyleneiodonium (DPI) and was insensitive to antagonists of other ROS
      producing enzyme systems including mitochondrial enzymes, cycloxygenase, and
      xanthine oxidase. NADPH oxidase 4 (Nox4) was found to be the most abundant
      isoform expressed in B16 cells, and its gene levels, as well as ROS generation,
      were enhanced by alpha-MSH. Interestingly, silencing Nox4 gene expression with
      Nox4 siRNA augmented melanin formation under basal conditions and after alpha-MSH
      stimulation, demonstrating that constitutive or stimulated Nox4-dependent ROS
      inhibits melanin formation. This process may be mediated by targeting the
      promoter region of a melanin synthesizing enzyme tyrosinase, because Nox4 siRNA
      enhanced tyrosinase promoter activity. Moreover, inhibition of tyrosinase mRNA
      expression in Nox4 siRNA-treated cells by blocking de novo mRNA and protein
      synthesis with actinomycin D and cycloheximide respectively indicates that Nox4
      repression induces melanogenesis by increasing tyrosinase gene expression. We
      also found that alpha-MSH activated its downstream signal transducer
      microphthalmia-associated transcription factor (MITF) to stimulate Nox4 gene
      expression. We thus identified a novel mechanism by MITF signaling that in turn
      stimulates Nox4 to drive ROS generation, thereby repressing melanin synthesis.
      Such sequence of actions appears to act as an internal feedback mechanism to fine
      tune melanin synthesis in response to exogenous challenges such as UV radiation.

PMID- 22401857
TI  - Novel properties of melanins include promotion of DNA strand breaks, impairment
      of repair, and reduced ability to damage DNA after quenching of singlet oxygen.
AB  - Melanins have been associated with the development of melanoma and its resistance
      to photodynamic therapy (PDT). Singlet molecular oxygen ((1)O(2)), which is
      produced by ultraviolet A solar radiation and the PDT system, is also involved.
      Here, we investigated the effects that these factors have on DNA damage and
      repair. Our results show that both types of melanin (eumelanin and pheomelanin)
      lead to DNA breakage in the absence of light irradiation and that eumelanin is
      more harmful than pheomelanin. Interestingly, melanins were found to bind to the
      minor grooves of DNA, guaranteeing close proximity to DNA and potentially causing
      the observed high levels of strand breaks. We also show that the interaction of
      melanins with DNA can impair the access of repair enzymes to lesions,
      contributing to the perpetuation of DNA damage. Moreover, we found that after
      melanins interact with (1)O(2), they exhibit a lower ability to induce DNA
      breakage; we propose that these effects are due to modifications of their
      structure. Together, our data highlight the different modes of action of the two
      types of melanin. Our results may have profound implications for cellular redox
      homeostasis, under conditions of induced melanin synthesis and irradiation with
      solar light. These results may also be applied to the development of protocols to
      sensitize melanoma cells to PDT.

PMID- 22401856
TI  - Reactive oxygen and nitrogen species in pulmonary hypertension.
AB  - Pulmonary vascular disease can be defined as either a disease affecting the
      pulmonary capillaries and pulmonary arterioles, termed pulmonary arterial
      hypertension, or a disease affecting the left ventricle, called pulmonary venous
      hypertension. Pulmonary arterial hypertension (PAH) is a disorder of the
      pulmonary circulation characterized by endothelial dysfunction, as well as
      intimal and smooth muscle proliferation. Progressive increases in pulmonary
      vascular resistance and pressure impair the performance of the right ventricle,
      resulting in declining cardiac output, reduced exercise capacity, right-heart
      failure, and ultimately death. While the primary and heritable forms of the
      disease are thought to affect over 5000 patients in the United States, the
      disease can occur secondary to congenital heart disease, most advanced lung
      diseases, and many systemic diseases. Multiple studies implicate oxidative stress
      in the development of PAH. Further, this oxidative stress has been shown to be
      associated with alterations in reactive oxygen species (ROS), reactive nitrogen
      species (RNS), and nitric oxide (NO) signaling pathways, whereby bioavailable NO
      is decreased and ROS and RNS production are increased. Many canonical ROS and NO
      signaling pathways are simultaneously disrupted in PAH, with increased expression
      of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and xanthine
      oxidoreductase, uncoupling of endothelial NO synthase (eNOS), and reduction in
      mitochondrial number, as well as impaired mitochondrial function. Upstream
      dysregulation of ROS/NO redox homeostasis impairs vascular tone and contributes
      to the pathological activation of antiapoptotic and mitogenic pathways, leading
      to cell proliferation and obliteration of the vasculature. This paper will review
      the available data regarding the role of oxidative and nitrosative stress and
      endothelial dysfunction in the pathophysiology of pulmonary hypertension, and
      provide a description of targeted therapies for this disease.

PMID- 22401858
TI  - Gpx4 ablation in adult mice results in a lethal phenotype accompanied by neuronal
      loss in brain.
AB  - Glutathione peroxidase 4 (Gpx4) is an antioxidant defense enzyme important in
      reducing hydroperoxides in membrane lipids and lipoproteins. Gpx4 is essential
      for survival of embryos and neonatal mice; however, whether Gpx4 is required for
      adult animals remains unclear. In this study, we generated a floxed Gpx4 mouse
      (Gpx4(f/f)), in which exons 2-4 of Gpx4 gene are flanked by loxP sites. We then
      cross-bred the Gpx4(f/f) mice with a tamoxifen (tam)-inducible Cre transgenic
      mouse (R26CreER mice) to obtain mice in which the Gpx4 gene could be ablated by
      tam administration (Gpx4(f/f)/Cre mice). After treatment with tam, adult
      Gpx4(f/f)/Cre mice (6-9 months of age) showed a significant reduction of Gpx4
      levels (a 75-85% decrease) in tissues such as brain, liver, lung, and kidney. Tam
      treated Gpx4(f/f)/Cre mice lost body weight and died within 2 weeks, indicating
      that Gpx4 is essential for survival of adult animals. Tam-treated Gpx4(f/f)/Cre
      mice exhibited increased mitochondrial damage, as evidenced by the elevated 4
      hydroxylnonenal (4-HNE) level, decreased activities of electron transport chain
      complexes I and IV, and reduced ATP production in liver. Tam treatment also
      significantly elevated apoptosis in Gpx4(f/f)/Cre mice. Moreover, tam-treated
      Gpx4(f/f)/Cre mice showed neuronal loss in the hippocampus region and had
      increased astrogliosis. These data indicate that Gpx4 is essential for
      mitochondria integrity and survival of neurons in adult animals.

PMID- 22401859
TI  - Nrf2-regulated phase II enzymes are induced by chronic ambient nanoparticle
      exposure in young mice with age-related impairments.
AB  - Many xenobiotic detoxifying (phase II) enzymes are induced by sublethal doses of
      environmental toxicants. However, these adaptive mechanisms have not been studied
      in response to vehicular-derived airborne nano-sized particulate matter (nPM).
      Because aging is associated with increased susceptibility to environmental
      toxicants, we also examined the expression of Nrf2-regulated phase II genes in
      middle-aged mice and their inducibility by chronic nPM. The nPM from vehicular
      traffic was collected in urban Los Angeles and reaerosolized for exposure of
      C57BL/6J male mice (3 and 18 months old) for 150 h over 10 weeks. Brain
      (cerebellum), liver, and lung were assayed by RT-PCR and/or Western blots for the
      expression of phase II enzymes, glutamate cysteine ligase (catalytic GCLC, and
      modifier GCLM subunits), NAD(P)H:quinone oxidoreductase 1 (NQO1), heme oxygenase
      1 (HO-1), and relevant transcription factors, NF-E2-related factor 2 (Nrf2), c
      Myc, Bach1. Chronic nPM exposure induced GCLC, GCLM, HO-1, NQO1 mRNA, and protein
      similarly in cerebellum, liver, and lung of young mice. Middle-aged mice had
      elevated basal levels, but showed impaired further induction by nPM. Similarly,
      Nrf2 increased with age and was induced by nPM in young but not old. c-Myc showed
      the same age and induction profile while the age increase in Bach1 was further
      induced by nPM. Chronic exposure to nanoparticles induced Nrf2-regulated
      detoxifying enzymes in brain (cerebellum), liver, and lung of young adult mice,
      indicating a systemic impact of nPM. In contrast, middle-aged mice did not
      respond above their elevated basal levels except for Bach1. The lack of induction
      of phase II enzymes in aging mice may be a model for the vulnerability of elderly
      to air pollution.

PMID- 22401861
TI  - Respite care after acquired brain injury: the well-being of caregivers and
      patients.
AB  - OBJECTIVE: To investigate satisfaction with respite care, the well-being of
      informal caregivers and patients with acquired brain injury (ABI) who receive
      respite care by day-care activity centers, and factors related to caregiver well
      being. DESIGN: Cross-sectional cohort study. SETTING: Adult day-care activity
      centers. PARTICIPANTS: A sample of caregivers and patients (N=108) with ABI (mean
      of 8y since injury) enrolled in 1 of 7 day-care activity centers. The sample
      consisted predominantly (70%) of stroke patients. INTERVENTION: Respite care by
      adult day-care activity centers. MAIN OUTCOME MEASURES: Well-being was defined in
      terms of life satisfaction (Life Satisfaction Questionnaire [LiSat-9]), emotional
      functioning (Hospital Anxiety and Depression Scale [HADS]), and caregiver burden
      (Caregiver Strain Index [CSI]). Factors related to well-being were personal,
      injury related, and psychological. RESULTS: Satisfaction with day-care activity
      center care was high for caregivers (7.8) and patients (8.1). Caregiver
      satisfaction with care was unrelated to caregiver well-being. Most caregivers
      (61%) showed low life satisfaction and high subjective burden (69%), and 33% of
      caregivers and 42% of the patients reported depressive symptoms. Caregiver well
      being was positively correlated with a high sense of mastery of caregivers and
      patients and low passive coping of the patient (LiSat-9 R(2)=.32; HADS R(2)=.55;
      CSI R(2)=.35). CONCLUSIONS: This study emphasizes the need for care for both
      caregivers and patients in the chronic phase after ABI. Although respite care is
      highly appreciated, it is not sufficient for caregivers to attain a healthy level
      of well-being. Results indicate that caregiver well-being might improve by
      targeting passive coping and mastery skills of caregivers and patients.
      Continuous support for both caregivers and patients is needed.

PMID- 22401860
TI  - MicroRNAs in B cell development and malignancy.
AB  - MicroRNAs are small RNA molecules that regulate gene expression and play critical
      roles in B cell development and malignancy. miRNA expression is important
      globally, as B cell specific knockouts of Dicer show profound defects in B cell
      development; and is also critical at the level of specific miRNAs. In this
      review, we discuss miRNAs that are involved in normal B cell development in the
      bone marrow and during B cell activation and terminal differentiation in the
      periphery. Next, we turn to miRNAs that are dysregulated during diseases of B
      cells, including malignant diseases and autoimmunity. Further study of miRNAs and
      their targets will lead to a better understanding of B cell development, and
      should also lead to the development of novel therapeutic strategies against B
      cell diseases.

PMID- 22401863
TI  - Structure based design of an in vivo active hydroxamic acid inhibitor of P.
      aeruginosa LpxC.
AB  - Lipid A is an essential component of the Gram negative outer membrane, which
      protects the bacterium from attack of many antibiotics. The Lipid A biosynthesis
      pathway is essential for Gram negative bacterial growth and is unique to these
      bacteria. The first committed step in Lipid A biosynthesis is catalysis by LpxC,
      a zinc dependent deacetylase. We show the design of an LpxC inhibitor utilizing a
      robust model which directed efficient design of picomolar inhibitors. Analysis of
      physiochemical properties drove design to focus on an optimal lipophilicity
      profile. Further structure based design took advantage of a conserved water
      network over the active site, and with the optimal lipophilicity profile, led to
      an improved LpxC inhibitor with in vivo activity against wild type Pseudomonas
      aeruginosa.

PMID- 22401862
TI  - Synthesis, crystal structures, in vitro biological evaluation of zinc(II) and
      bismuth(III) complexes of 2-acetylpyrazine N(4)-phenylthiosemicarbazone.
AB  - Two metal complexes formulated as [Zn(L)(2)](2).H(2)O (1) and
      [Bi(L)(NO(3))(2)(CH(3)OH)] (2), where HL=2-acetylpyrazine N(4)
      phenylthiosemicarbazone, have been synthesized and characterized by elemental
      analysis, IR, MS, NMR and single-crystal X-ray diffraction studies. Biological
      studies, carried out in vitro against selected bacteria and the K562 leukemia
      cell lines, respectively, have shown that the free ligand and its two complexes
      may be endowed with important biological properties, especially HL with MIC=3.90
      MUg/mL against Pseudomonas aeruginosa, the zinc(II) complex 1 with IC(50)=1.0 MUM
      against K562 leukemia cell lines, respectively. The compounds HL and 1 may exert
      their cytotoxicity activity via induced loss of mitochondria membrane potential
      (MMP).

PMID- 22401864
TI  - Discovery of oxazole-based PDE4 inhibitors with picomolar potency.
AB  - Optimization of oxazole-based PDE4 inhibitors has led to the discovery of a
      series of quinolyl oxazoles, with 4-benzylcarboxamide and 5-alpha-aminoethyl
      groups which exhibit picomolar potency against PDE4. Selectivity profiles and in
      vivo biological activity are also reported.

PMID- 22401865
TI  - Synthesis, resolution and anticonvulsant activity of chiral N-1'-ethyl,N-3'-(1
      phenylethyl)-(R,S)-2'H,3H,5'H-spiro-(2-benzofuran-1,4'-imidazolidine)-2',3,5'
      trione diastereomers.
AB  - Four new N-1',N-3'-disubstituted-2'H,3H,5'H-spiro-(2-benzofuran-1,4'
      imidazolidine)-2',3,5'-triones bearing a chiral N-3' substituent were
      synthesized, resolved and their anticonvulsant activity was obtained and
      determined that the activity was not stereoselective.

PMID- 22401866
TI  - Scabronine M, a novel inhibitor of NGF-induced neurite outgrowth from PC12 cells
      from the fungus Sarcodon scabrosus.
AB  - A novel cyathane diterpenoid, designated scabronine M (1), was isolated from the
      fruiting bodies of the mushroom Sarcodon scabrosus together with 10 known
      compounds. The structure of the new compound was elucidated on the basis of
      extensive spectroscopic analysis including 2D-NMR. Among these compounds, only
      scabronine M (1) significantly inhibited dose-dependently NGF-induced neurite
      outgrowth in PC12 cells without cytotoxicity, possibly through suppressing the
      phosphorylation of the receptor Trk A and the extracellular signal regulated
      kinases (ERK). This is the first report of novel neurite outgrowth-inhibiting
      activity in PC12 cells of this group of diterpenoids.

PMID- 22401867
TI  - Sustained viral load reduction in treatment-naive HCV genotype 1 infected
      patients after therapeutic peptide vaccination.
AB  - BACKGROUND: Novel antivirals augment treatment efficacy in chronic HCV infection,
      to overcome limitations on safety profile alternative approaches are warranted.
      The effect of a therapeutic peptide vaccine on HCV viral load was investigated in
      treatment-naive genotype 1 HCV patients. METHODS: Fifty patients received 8
      intradermal IC41 vaccinations biweekly with topical application of the TLR7
      agonist imiquimod (Group A). In Group B, 21 patients received a condensed
      schedule of 16 subcutaneous vaccinations weekly without imiquimod. RESULTS: At
      Week 16 Group A (n=44) showed a statistically significant (p=0.0013) HCV viral
      load decline of 0.21 log. 24 weeks after the last vaccination the viral load
      decreased by 0.47 log (p<0.0001) in 34 subjects. This effect was more pronounced
      in 17 patients with high baseline HCV (>2*10(6)IU/ml) with a 0.61 log decline,
      which was statistically significant (p<0.02) starting two weeks after the third
      vaccination. No apparent effect on HCV viral load was observed in Group B (n=21).
      In Group A eight patients (24%) showed a viral load response defined as a decline
      of >0.8 log. Overall, about 30-55% of patients showed T cell responses during the
      vaccination series and up to six months in both groups. No significant
      correlations between the HCV viral load decrease and T cell immune response were
      detected. CONCLUSIONS: This is the first report on a significant antiviral effect
      of a peptide vaccine in HCV infected patients. Response kinetics with increased
      HCV RNA decline 24 weeks after the last IC41 vaccination is encouraging.

PMID- 22401868
TI  - Pediatric influenza immunization in an integrated safety net health care system.
AB  - OBJECTIVE: In 2008 the Advisory Committee on Immunization Practices (ACIP) of the
      Centers for Disease Control and Prevention (CDC) recommended that all children
      aged 6 months to 18 years receive annual influenza vaccine. Full pediatric
      influenza administration has proven difficult. We compared rates of full
      influenza immunization between a safety net health care system and CDC sentinel
      sites and evaluated sociodemographic factors associated with full influenza
      immunization. PATIENTS AND METHODS: We matched influenza immunization data for
      2008-2009 from a health care system immunization registry with patient
      demographic/billing data and compared rates to CDC sentinel sites using bivariate
      analysis. We evaluted immunization rates by patient characteristics using
      multivariate analysis. RESULTS: Full influenza immunization was achieved in 32%
      of Denver Health (DH) children compared to 12% at the CDC sites (p<0.001). The
      largest differences occurred in children aged 11-12 and 13-18 years, 47% DH vs
      12% CDC sites, and 33% DH vs 9% CDC sites respectively, (p<0.001 for both). In
      multivariate analysis, DH children were more likely to be immunized if they were
      Asian, Odds Ratio (OR) 1.59 95%CI (CI) 1.32-1.91, or Hispanic OR 1.18 CI 1.07
      1.30, compared to white, spoke Spanish OR 1.19 CI 1.13-1.26, or other non-English
      language OR 2.05 CI 1.80-2.34, and had a greater number of visits for well care
      OR 2.86 CI 2.74-2.98 and sick/follow-up care OR 1.59 CI 1.56-1.62, during the
      influenza season. They were less likely to be immunized if they had commercial
      insurance OR 0.68 CI 0.62-0.75 or were uninsured OR 0.77 CI 0.72-0.80, compared
      to Medicaid/SCHIP. CONCLUSIONS: Using immunization registry prompts, standing
      orders, multiple sites and visit types for immunization, an integrated safety net
      health care system had higher full influenza immunization rates than the CDC
      sentinel sites singularly or collectively. These procedures can be applied
      elsewhere to improve influenza immunization rates.

PMID- 22401869
TI  - Bisphosphonate-related osteonecrosis of the jaws: study of the staging system in
      a series of clinical cases.
AB  - OBJECTIVE: The aim of this study was to validate the classification of
      bisphosphonate-related osteonecrosis of the jaws (BRONJ) published in 2009(17) in
      a series of cases. MATERIAL AND METHODS: This retrospective clinical study
      included a series of 102 cases (81%) of intravenous BRONJ (iBRONJ, group 1) and
      24 cases (19%) of oral BRONJ (oBRONJ, group 2). We recorded all patients'
      symptoms and clinical findings and classified each patient into a BRONJ stage (0
      3; stage 0=non-exposed BRONJ). RESULTS: Most BRONJ cases (n=120, 95.2%) could be
      classified according to the proposed stages. Exposed necrotic areas of bone were
      more prevalent in group 1 than in group 2 (p<0.05). In contrast, we observed more
      BRONJ cases without areas of exposed bone in group 2 (n=12, 50%) than in group 1
      (n=14, 13.7%; p<0.05). We could not assign six cases to any of the proposed
      stages. These cases had no areas of exposed necrotic bone, but had mandibular
      fractures, extra-oral fistula or affected maxillary sinuses. CONCLUSIONS: In our
      series, iBRONJ cases showed more advanced stages of BRONJ than did oBRONJ cases.
      We found few cases that could not be classified into any proposed stage because
      they had findings associated with stages 0 and 3 but lacked exposed necrotic
      bone.

PMID- 22401870
TI  - Intensity-modulated radiotherapy improves outcomes in postoperative patients with
      squamous cell carcinoma of the oral cavity.
AB  - OBJECTIVES: We compared the outcomes and survival rates of patients with oral
      cavity squamous cell carcinoma receiving postoperative conventional radiotherapy
      (RT) or intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: From
      January 2005 to September 2008, medical records of 131 consecutive patients with
      oral cancer receiving postoperative radiotherapy in the Department of Radiation
      Oncology of National Cheng Kung University Hospital were reviewed. Patients were
      divided into two groups according to the administration of postoperative
      conventional RT or IMRT. The loco-regional control, survival, and other
      prognostic factors were compared. RESULTS: The 3-year Kaplan-Meier estimates of
      overall survival for patients receiving conventional RT and IMRT groups were
      51.2% vs. 69.4% (p=0.079), respectively. The 3-year local-regional control (53.5%
      vs. 76.3%; p=0.020) and disease-free survival rates (47.8% vs. 70.0%; p=0.027)
      were significantly increased in the IMRT group. This retrospective study also
      identified that extracapsular spreading, margin positive/close (<= 2mm), more
      advanced T stage (T3-4 vs. T1-2), and conventional RT method were associated with
      worse prognosis. CONCLUSIONS: The addition of chemotherapy to adjuvant
      radiotherapy is recommended in patients with above risk factors. Our result
      underscores that IMRT should be considered to apply to OSCC patients referred for
      postoperative treatment.

PMID- 22401871
TI  - Premetastatic vasculogenesis in oral squamous cell carcinoma xenograft-draining
      lymph nodes.
AB  - OBJECTIVE: To study vascular anatomy on oral cancer-draining lymph nodes before
      metastasis in mice. MATERIAL AND METHODS: Cell lines: highly lymph metastatic
      oral squamous cell carcinoma SASL1m and non-metastatic human adenoid cystic
      carcinoma ACC2. Bone marrow transplants and xenografts: Nude mice were lethally
      irradiated and transplanted with bone marrow cells from EGFP(+) mice. SASL1m or
      ACC2 cells were implanted in the tongue. Non-xenografted mice were used as
      controls. In addition, we injected conditioned medium from SASL1m or ACC2 in
      transplanted mice. Immunohistochemistry: Primary tumors and neck lymph nodes were
      resected and stained with anti-mouse Podoplanin and CD31. Images were visualized
      in a confocal microscope. Image analysis: Areas covered by EGFP, CD31 and
      Podoplanin were measured and compared statistically. Expression microarrays:
      Transcriptomic microarray analysis compared SASL1 to ACC2 cells. Interactomes
      were generated to reveal altered pathways. RESULTS: SASL1m cells induced the
      assemblage of blood vessels in cancer-free, tumor-draining lymph nodes. These
      blood vessels incorporated bone marrow-derived EGFP(+)CD31(+) cells. Notably,
      SASL1m-conditioned medium induced a similar reaction. Non-metastatic cells failed
      to produce any change. Microarray and pathway analyses revealed the upregulation
      of Transforming Growth Factor-beta, Lysyl Oxidase-like 2, Slit homolog 3 and
      Protease Serine 22. The upregulation of these genes was confirmed in xenografts.
      CONCLUSIONS: This study suggests that a blood supply for new tumors is
      established in lymph nodes before metastasis. It also suggests that premetastatic
      vasculogenesis and primary tumor angiogenesis may be mediated by different
      mechanisms.

PMID- 22401872
TI  - Weight loss is effective for symptomatic relief in obese subjects with knee
      osteoarthritis independently of joint damage severity assessed by high-field MRI
      and radiography.
AB  - OBJECTIVE: With an increasing prevalence of older and obese citizens, the
      problems of knee osteoarthritis (KOA) will escalate. Weight loss is recommended
      for obese KOA patients and in a majority of cases this leads to symptomatic
      relief. We hypothesized that pre-treatment structural status of the knee joint,
      assessed by radiographs, 1.5 T magnetic resonance imaging (MRI) and knee-joint
      alignment, may influence the symptomatic changes following a significant weight
      reduction. DESIGN: Patients were recruited from a Department of Rheumatology.
      Eligibility criteria were age above 50 years, body mass index >= 30 kg/m(2),
      primary KOA diagnosed according to the American College of Rheumatology (ACR)
      criteria and having verified structural damage. Patients underwent a 16 weeks
      dietary programme with formula products and counselling. MRI and radiographs of
      the most symptomatic knee were obtained at baseline and assessed for structural
      damage using the Boston-Leeds Osteoarthritis of the Knee Score, minimum joint
      space width and Kellgren-Lawrence score. Imaging variables, muscle strength and
      degree of alignment, were examined as predictors of changes in Knee
      Osteoarthritis Outcome Score (KOOS) and Outcome Measures in Rheumatoid Arthritis
      Clinical Trials (OMERACT) - Osteoarthritis Research Society International (OARSI)
      Responder Criterion. RESULTS: Structural damage at baseline assessed by imaging,
      muscle strength or knee-joint alignment showed no statistically significant
      association to changes in KOOS pain and function in daily living (r <= 0.13;
      P>0.05) or the OMERACT-OARSI Responder Criterion (OR 0.48-1.68; P-values >=
      0.13). CONCLUSIONS: Presence of joint damage did not preclude symptomatic relief
      following a clinically relevant weight loss in older obese patients with KOA.
      Neither muscle strength nor knee-joint alignment was associated with the degree
      of symptomatic relief.

PMID- 22401873
TI  - Coll2-1, Coll2-1NO2 and myeloperoxidase serum levels in erosive and non-erosive
      osteoarthritis of the hands.
AB  - OBJECTIVE: Erosive osteoarthritis of the hand (EHOA) is thought to be an
      aggressive variant of hand osteoarthritis (HOA) characterised by prominent local
      inflammation and radiographic aspects of bone erosions in interphalangeal (IP)
      joints. However, rare studies have until now investigated the value of biomarkers
      in these patients. Thus, we determined Coll2-1, a marker of type II collagen
      denaturation, its nitrated form (Coll2-1NO2) and myeloperoxidase (MPO) levels in
      serum of patients with EHOA vs non-EHOA and subsequently evaluated their
      relationships with disease indices of severity and activity. METHODS: Coll2-1,
      Coll2-1NO2 and MPO were measured using specific immunoassays in 82 patients, 57
      with EHOA, all females, median age 59 (41-74 yrs) and 20 with non-EHOA, all
      females, median age 55 (43-73 yrs), fulfilling the American College of
      Rheumatology (ACR) criteria for hand OA. EHOA was characterized by the presence
      of at least one central bone erosion on radiograph in the IP joints. Patients
      were also evaluated for disease duration, number of affected (swollen and painful
      or tender) joints, radiographic score (RS) by Kallman scale and high sensitivity
      C-reactive protein (hsCRP). RESULTS: Serum levels of MPO were higher in EHOA
      (230.0 +/- 152.1 ng/ml) than in non-EHOA (160.2 +/- 111.5 ng/ml, P=0.037). Coll2
      1NO2 levels trended towards an elevation in EHOA compared non-EHOA (0.40 +/- 0.86
      vs 0.22 +/- 0.14 nmol/l, P=0.06), while Coll2-1 levels were not different.
      Correlations were found for disease duration and both MPO (R(2)=0.48, P=0.001)
      and Coll2-1NO2 (R(2)=0.73, P=0.01) after the splitting of the population in
      subgroups according to a cut off value above the 50th percentile. A correlation
      was found between hsCRP and MPO (R(2)=0.57, P=0.01). CONCLUSIONS: This study
      clearly demonstrates an elevation of some serum biomarkers in EHOA, in comparison
      with non-EHOA. In particular, MPO, hsCRP and the ratio Coll2-1NO2/Coll2-1
      discriminated the two subsets of hand osteoarthritis (HOA), and a trend was also
      observed for Coll2-1NO2. These data suggest that these biomarkers could be
      helpful for the diagnosis of EHOA.

PMID- 22401874
TI  - Thermal analysis and calorimetry.

PMID- 22401876
TI  - A rare cause of hypoglycemia in a type 2 diabetic patient: insulinoma.
AB  - Recurrent episodes of hypoglycemia in patients with diabetes are often associated
      with the ongoing treatment regimen. However, despite changes in treatment
      modalities, assessment of the causes of hypoglycemia in nondiabetic patients in
      the presence of severe and recurrent hypoglycemia is very important. The
      treatment that had been provided for 6 years in a 67-year-old female patient with
      type 2 diabetes mellitus was discontinued due to hypoglycemic episodes that
      presented for the previous 2 years. The patient experienced persistent
      hypoglycemia after cessation of the treatment and was hospitalized for further
      examination. Spontaneous hypoglycemia with a final diagnosis of insulinoma was
      established following histopathologic evaluation and was relieved postoperation.
      Insulinoma is rarely encountered as a cause of hypoglycemia in patients with type
      2 diabetes. Insulin-secreting tumors should be considered where hypoglycemic
      episodes occur despite discontinuation of insulin and other antidiabetic
      treatment with endogenous hyperinsulinemia being noncompliant with the blood
      glycemic levels.

PMID- 22401877
TI  - Placental expression of anti-angiogenic proteins in mirror syndrome: a case
      report.
AB  - Mirror syndrome is a rare disorder in which fetal hydrops is associated with
      maternal oedema, proteinuria and hypertension. The aetiology of the maternal
      condition is unknown, but it is thought to be related to preeclampsia. Few
      descriptions exist of placental morphology in mirror syndrome, but placentomegaly
      is consistently observed. In this case placental morphology showed villous oedema
      and syncytial nuclear aggregates where villi were in direct contact.
      Immunoperoxidase staining for VEGFR1 and Endoglin was more intense in mirror
      syndrome compared to gestational-age matched controls,and at a similar level to a
      case of preeclampsia. Placentally-derived anti-angiogenic factors may be involved
      in the pathogenesis of mirror syndrome.

PMID- 22401875
TI  - Synthetic cell surface receptors for delivery of therapeutics and probes.
AB  - Receptor-mediated endocytosis is a highly efficient mechanism for cellular uptake
      of membrane-impermeant ligands. Cells use this process to acquire nutrients,
      initiate signal transduction, promote development, regulate neurotransmission,
      and maintain homeostasis. Natural receptors that participate in receptor-mediated
      endocytosis are structurally diverse, ranging from large transmembrane proteins
      to small glycolipids embedded in the outer leaflet of cellular plasma membranes.
      Despite their vast structural differences, these receptors share common features
      of binding to extracellular ligands, clustering in dynamic membrane regions that
      pinch off to yield intracellular vesicles, and accumulation of receptor-ligand
      complexes in membrane-sealed endosomes. Receptors typically dissociate from
      ligands in endosomes and cycle back to the cell surface, whereas internalized
      ligands are usually delivered into lysosomes, where they are degraded, but some
      can escape and penetrate into the cytosol. Here, we review efforts to develop
      synthetic cell surface receptors, defined as nonnatural compounds, exemplified by
      mimics of cholesterol, that insert into plasma membranes, bind extracellular
      ligands including therapeutics, probes, and endogenous proteins, and engage
      endocytic membrane trafficking pathways. By mimicking natural mechanisms of
      receptor-mediated endocytosis, synthetic cell surface receptors have the
      potential to function as prosthetic molecules capable of seamlessly augmenting
      the endocytic uptake machinery of living mammalian cells.

PMID- 22401878
TI  - Sex differences in the effect of high-fat diet feeding on rat white adipose
      tissue mitochondrial function and insulin sensitivity.
AB  - Obesity-induced mitochondrial dysfunction in white adipose tissue (WAT) leads to
      a dysregulation of adipokine secretion, which is involved in insulin resistance
      development. Taking into account the sex differences previously found both in
      mitochondrial function and for the insulin sensitivity profile in different
      tissues, the aim of this study was to investigate whether a sex-dependent effect
      of a long-term high-fat diet (HFD) feeding exists on WAT mitochondrial function.
      Indeed, HFD effects on the levels of the key components of the insulin and
      adiponectin signaling pathways, and the consequences of these effects on the
      systemic profile of insulin sensitivity were also studied. Wistar rats of both
      sexes were fed a standard diet or an HFD. Serum markers of insulin sensitivity,
      protein, and mRNA levels of the main elements of the insulin and adiponectin
      signaling pathways, and the markers of mitochondrial function and biogenesis,
      were measured. Our results indicate that different physiological strategies are
      adopted by male and female rats in response to HFD. In this regard, HFD induced
      mitochondrial proliferation in males and mitochondrial differentiation in
      females, as well as a greater retroperitoneal WAT expandability capacity, which
      allows them to preserve a better insulin sensitivity profile than male rats for
      both control and HFD groups. Moreover, female WAT showed a decrease in
      adiponectin and insulin signaling pathway element levels. This sexual dimorphism
      suggests that there are different strategies for retroperitoneal WAT to maintain
      the energetic and metabolic homeostasis in response to HFD feeding.

PMID- 22401880
TI  - Assessment of potential asbestos exposures from jet engine overhaul work.
AB  - Asbestos fibers have been used in a wide variety of products and numerous studies
      have shown that exposures from the use or manipulation of these products can vary
      widely. Jet engines contained various components (gaskets, clamps, o-rings and
      insulation) that contained asbestos that potentially could release airborne
      fibers during routine maintenance or during an engine overhaul. To evaluate the
      potential exposures to aircraft mechanics, a Pratt & Whitney JT3D jet engine was
      obtained and overhauled by experienced mechanics using tools and work practices
      similar to those used since the time this engine was manufactured. This study has
      demonstrated that the disturbance of asbestos-containing gaskets, o-rings, and
      other types of asbestos-containing components, while performing overhaul work to
      a jet engine produces very few airborne fibers, and that virtually none of these
      aerosolized fibers is asbestos. The overhaul work was observed to be dirty and
      oily. The exposures to the mechanics and bystanders were several orders of
      magnitude below OSHA exposure regulations, both current and historic. The data
      presented underscore the lack of risk to the health of persons conducting this
      work and to other persons in proximity to it from airborne asbestos.

PMID- 22401879
TI  - The health benefits of dietary fiber: beyond the usual suspects of type 2
      diabetes mellitus, cardiovascular disease and colon cancer.
AB  - Dietary fiber (DF) is deemed to be a key component in healthy eating. DF is not a
      static collection of undigestible plant materials that pass untouched or
      unencumbered through the gastrointestinal (GI) tract; instead, DFs are a vast
      array of complex saccharide-based molecules that can bind potential nutrients and
      nutrient precursors to prevent their absorption. Some DFs are fermentable, and
      the GI tract catabolism leads to the generation of various bioactive materials,
      such as short-chain fatty acids (SCFAs), that can markedly augment the GI tract
      biomass and change the composition of the GI tract flora. The health benefits of
      DFs include the prevention and mitigation of type 2 diabetes mellitus,
      cardiovascular disease and colon cancer. By modulating food ingestion, digestion,
      absorption and metabolism, DFs reduce the risk of hyperlipidemia,
      hypercholesterolemia and hyperglycemia. Emerging research has begun to
      investigate the role of DFs in immunomodulation. If substantiated, DFs could
      facilitate many biologic processes, including infection prevention and the
      improvement of mood and memory. This review describes the accepted physiologic
      functions of DFs and explores their new potential immune-based actions.

PMID- 22401881
TI  - High STOP-Bang score indicates a high probability of obstructive sleep apnoea.
AB  - BACKGROUND: The STOP-Bang questionnaire is used to screen patients for
      obstructive sleep apnoea (OSA). We evaluated the association between STOP-Bang
      scores and the probability of OSA. METHODS: After Institutional Review Board
      approval, patients who visited the preoperative clinics for a scheduled inpatient
      surgery were approached for informed consent. Patients answered STOP
      questionnaire and underwent either laboratory or portable polysomnography (PSG).
      PSG recordings were scored manually. The BMI, age, neck circumference, and gender
      (Bang) were documented. Over 4 yr, 6369 patients were approached and 1312 (20.6%)
      consented. Of them, 930 completed PSG, and 746 patients with complete data on PSG
      and STOP-Bang questionnaire were included for data analysis. RESULTS: The median
      age of 746 patients was 60 yr, 49% males, BMI 30 kg m(-2), and neck circumference
      39 cm. OSA was present in 68.4% with 29.9% mild, 20.5% moderate, and 18.0% severe
      OSA. For a STOP-Bang score of 5, the odds ratio (OR) for moderate/severe and
      severe OSA was 4.8 and 10.4, respectively. For STOP-Bang 6, the OR for
      moderate/severe and severe OSA was 6.3 and 11.6, respectively. For STOP-Bang 7
      and 8, the OR for moderate/severe and severe OSA was 6.9 and 14.9, respectively.
      The predicted probabilities for moderate/severe OSA increased from 0.36 to 0.60
      as the STOP-Bang score increased from 3 to 7 and 8. CONCLUSIONS: In the surgical
      population, a STOP-Bang score of 5-8 identified patients with high probability of
      moderate/severe OSA. The STOP-Bang score can help the healthcare team to stratify
      patients for unrecognized OSA, practice perioperative precautions, or triage
      patients for diagnosis and treatment.

PMID- 22401882
TI  - Mapping the genetic basis of ecologically and evolutionarily relevant traits in
      Arabidopsis thaliana.
AB  - There has been a long standing interest in the relationship between genetic and
      phenotypic variation in natural populations, in order to understand the genetic
      basis of adaptation and to discover natural alleles to improve crops. Here we
      review recent developments in mapping approaches that have significantly improved
      our ability to identify causal polymorphism explaining natural variation in
      ecological and evolutionarily relevant traits. However, challenges in
      interpreting these discoveries remain. In particular, we need more detailed
      transcriptomic, epigenomic, and gene network data to help understand the
      mechanisms behind identified associations. Also, more studies need to be
      performed under field conditions or using experimental evolution to determine
      whether polymorphisms identified in the lab are relevant for adaptation and
      improvement under natural conditions.

PMID- 22401883
TI  - Dufour's gland possible role in the evolution of sting morphology and function in
      hover wasps (Hymenoptera Stenogastrinae).
AB  - The sting is the most effective defense of social Hymenoptera against vertebrate
      predators but in the hover wasps (subfamily Stenogastrinae) it is scarcely used.
      In these wasps a quite enlarged Dufour's gland and the extensive use of its
      secretion in the peculiar rearing of the larvae and defense determined important
      morphological modifications of the sting structure. Connecting anatomical and
      morphological data with behavioral observations we determined that in these wasps
      the Dufour's gland secretion is attached to the egg during oviposition but can be
      also channeled to the outside via the sting when it is collected by adult females
      for larval rearing or construction of the nest ant guards. The anatomical
      modifications of the sting reduced the function of the sting as a defensive
      weapon in hover wasps.

PMID- 22401884
TI  - Neuropeptides in insect mushroom bodies.
AB  - Owing to their experimental amenability, insect nervous systems continue to be in
      the foreground of investigations into information processing in - ostensibly -
      simple neuronal networks. Among the cerebral neuropil regions that hold a
      particular fascination for neurobiologists are the paired mushroom bodies, which,
      despite their function in other behavioral contexts, are most renowned for their
      role in learning and memory. The quest to understand the processes that underlie
      these capacities has been furthered by research focusing on unraveling
      neuroanatomical connections of the mushroom bodies and identifying key players
      that characterize the molecular machinery of mushroom body neurons. However, on a
      cellular level, communication between intrinsic and extrinsic mushroom body
      neurons still remains elusive. The present account aims to provide an overview on
      the repertoire of neuropeptides expressed in and utilized by mushroom body
      neurons. Existing data for a number of insect representatives is compiled and
      some open gaps in the record are filled by presenting additional original data.

PMID- 22401886
TI  - Peripheral blood stem cell transplantation or bone marrow transplant in
      allogeneic settings: which should be chosen?

PMID- 22401887
TI  - Oxidative stress in patients with primary insomnia.
AB  - OBJECTIVE: Many physiological and pathological processes, such as infections,
      environmental toxins, and ionizing radiation increase bodily concentrations of
      oxidizing substances, known as free radicals, which lead to neurodegenerative
      disorders. Sleep is one of the most important factors contributing to health;
      however, insomnia is among the most prevalent health complaints. METHODS: In this
      study, for the first time in the literature, we investigated the effects of
      primary insomnia on certain oxidative stress biomarkers. For this purpose,
      glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and myeloperoxidase
      (MPO) activities and levels of reduced glutathione (GSH) and malondialdehyde
      (MDA) were measured in 30 patients with primary insomnia and 30 healthy
      volunteers RESULTS: Our results show that the patients with primary insomnia had
      significantly lower GSH-Px activity and higher MDA levels compared with the
      controls. CONCLUSION: These results may indicate the important role of sleep in
      attenuating oxidative stress.

PMID- 22401885
TI  - The ciliary transition zone: from morphology and molecules to medicine.
AB  - Researchers from various disciplines, including cell and developmental biology,
      genetics and molecular medicine, have revealed an exceptional diversity of
      cellular functions that are mediated by cilia-dependent mechanisms. Recent
      studies have directed our attention to proteins that localize to the ciliary
      transition zone (TZ), a small evolutionarily conserved subcompartment that is
      situated between the basal body (BB) and the more distal ciliary axoneme. These
      reports shed light on the roles of TZ proteins in ciliogenesis, ciliary protein
      homeostasis and specification of ciliary signaling, and pave the way for
      understanding their contribution to human ciliopathies. In this review, we
      describe the interplay of multimeric protein complexes at the TZ, integrating
      morphological, genetic and proteomic data towards an account of TZ function in
      ciliary physiology.

PMID- 22401888
TI  - Early phase drug development for treatment of chronic pain--options for clinical
      trial and program design.
AB  - Due to high prevalence and unmet medical need, chronic pain has become an
      important area for development of new medicines. Chronic pain disorders are
      heterogeneous with regard to pathophysiological mechanisms and clinical
      presentation. While a mechanism-based classification of pain is generally
      advocated, it is not yet applicable for diagnostic use. Many new analgesic drug
      candidates believed to act on scientifically relevant pain targets have failed to
      show efficacy in clinical trials. These might be true observations of inferior
      efficacy and/or safety. However, in part, these failures may be due to
      difficulties with selection of an appropriate study population and/or appropriate
      doses. For a new chemical entity (NCE) with a novel pharmacological mechanism,
      the only guidance for selection of study population and doses is often based on
      preclinical data. Thus, there may be considerable uncertainty in defining the
      population with a pain generating mechanism targeted by the NCE. Therefore,
      further exploration of the right population and dose may be needed in early
      clinical phase why alternatives to conventional trial designs may be considered.
      We have reviewed characteristics of three alternative design options from an
      early (Phase 2) drug development perspective; enriched enrolment, dose titration
      and adaptive dosing. The advantages and disadvantages of each type of study
      design were analyzed and discussed from a clinical development program
      perspective. It is concluded that these designs can be useful in addressing
      different types of issues in early development of novel analgesic drugs for
      chronic pain.

PMID- 22401889
TI  - The allure of the maverick.

PMID- 22401890
TI  - Anthocyanins.

PMID- 22401891
TI  - The function of the sawfish's saw.

PMID- 22401892
TI  - Escape behavior: linking neural computation to action.
AB  - A new study uses a combination of physiological and optogenetic techniques to
      identify visual neurons in fruit flies that detect approaching objects, and whose
      activation is integral in escaping an oncoming threat.

PMID- 22401893
TI  - Meiosis: mouse eggs do their anaphase topsy-turvy.
AB  - The meiotic separation of sister chromatids in mature metaphase II mouse eggs is
      observed to depend initially on spindle lengthening (Anaphase B), then on
      microtubule shortening (Anaphase A). Having Anaphase B precede Anaphase A may be
      the mechanism by which mammalian eggs can generate a haploid chromosome number
      but without the loss of too much cytoplasm.

PMID- 22401894
TI  - Motor memory: when plans speak louder than actions.
AB  - A new study demonstrates that separate motor memories can be learned and
      remembered for two physically identical movements, provided that those movements
      have different goals.

PMID- 22401895
TI  - Sliding clamps: an open and shut case?
AB  - Molecular events in the clamp-loading reaction pathway of DNA replication are
      revealed by new crystal structures of bacteriophage T4 clamp loader-clamp-DNA
      complexes that capture two distinct conformations with the clamp open and closed.

PMID- 22401896
TI  - Speech development: toddlers don't mind getting it wrong.
AB  - A recent study has found that toddlers do not compensate for an artificial
      alteration in a vowel they hear themselves producing. This raises questions about
      how young children learn speech sounds.

PMID- 22401897
TI  - C(4) photosynthesis: need a gene? Borrow one!
AB  - Horizontal gene transfer has been increasingly documented between eukaryotes, but
      a new study suggests a much larger role for horizontal gene transfer in
      physiological adaption through the transfer of photosynthetic pathway genes.

PMID- 22401898
TI  - Visual perception: understanding visual cues to depth.
AB  - A new study shows that, in vision, object blur can be a more accurate depth cue
      than stereo disparity.

PMID- 22401899
TI  - Evolution: return of the ant supersoldiers.
AB  - An ancient developmental potential to form 'supersoldiers' facilitates the
      recurrent evolution of this subcaste in various species of Pheidole ants.

PMID- 22401900
TI  - Organization and reorganization of sensory-deprived cortex.

PMID- 22401901
TI  - Primary solid papillary tumor of the liver.
AB  - Solid papillary tumor (SPT) is an uncommon lesion of the pancreas whose origin
      and behavior are poorly understood. Very rare cases of primary extra-pancreatic
      SPTs have been described, and their clinical, histological, immunophenotypic and
      ultrastructural features seem to be similar to those arising in the pancreas.
      Here we report a case of primitive SPT of the liver, the second case described in
      the literature so far.

PMID- 22401902
TI  - The coherence problem with the Unified Neutral Theory of Biodiversity.
AB  - The Unified Neutral Theory of Biodiversity (UNTB), proposed as an alternative to
      niche theory, has been viewed as a theory that species coexist without niche
      differences, without fitness differences, or with equal probability of success.
      Support is claimed when models lacking species differences predict highly
      aggregated metrics, such as species abundance distributions (SADs) or species
      area distributions (SARs). Here, I summarize why UNTB generates confusion, and is
      not actually relevant to niche theory (i.e. an explanation for why and how many
      species coexist). Equal probability is not a theory, but lack of one; it does not
      include or exclude any process relevant to coexistence of competitors. Models
      lacking explicit species can make useful predictions, but this does not support
      neutral theory. I provide s suggestions that could help reduce confusion
      generated by the debate.

PMID- 22401903
TI  - Modestly increased use of colonoscopy when copayments are waived.
AB  - BACKGROUND & AIMS: Colorectal cancer (CRC) screening with colonoscopy often
      requires expensive copayments from patients. The 2010 Patient Protection and
      Affordable Care Act mandated elimination of copayments for CRC screening,
      including colonoscopy, but little is known about the effects of copayment
      elimination on use. The University of Texas employee, retiree, and dependent
      health plan instituted and promoted a waiver of copayments for screening
      colonoscopies in fiscal year (FY) 2009; we examined the effects of removing cost
      sharing on colonoscopy use. METHODS: We conducted a retrospective cohort study of
      59,855 beneficiaries of the University of Texas employee, retiree, and dependent
      health plan, associated with 16 University of Texas health and nonhealth
      campuses, ages 50-64 years at any point in FYs 2002-2009 (267,191 person-years of
      follow-up evaluation). The primary outcome was colonoscopy incidence among
      individuals with no prior colonoscopy. We compared the age- and sex-standardized
      incidence ratios for colonoscopy in FY 2009 (after the copayment waiver) with the
      expected incidence for FY 2009, based on secular trends from years before the
      waiver. RESULTS: The annual incidence of colonoscopy increased to 9.5% after the
      copayment was waived, compared with an expected incidence of 8.0% (standardized
      incidence ratio, 1.18; 95% confidence interval, 1.14-1.23; P < .001). After
      adjusting for age, sex, and beneficiary status, the copayment waiver remained
      significantly associated with greater use of colonoscopy, with an adjusted hazard
      ratio of 1.19 (95% confidence interval, 1.12-1.26). CONCLUSIONS: Waiving
      copayments for colonoscopy screening results in a statistically significant, but
      modest (1.5%), increase in use. Additional strategies beyond removing financial
      disincentives are needed to increase use of CRC screening.

PMID- 22401904
TI  - Systematic review: patterns of reflux-induced symptoms and esophageal endoscopic
      findings in large-scale surveys.
AB  - BACKGROUND & AIMS: This systematic review assesses findings of endoscopic surveys
      in the general population with regard to gastroesophageal reflux disease (GERD).
      METHODS: Systematic searches were conducted in PubMed and EMBASE. Authors were
      contacted for additional, unpublished data. RESULTS: Data on 61,281 individuals
      were included from 3 general population studies (Kalixanda study [Sweden], Loiano
      Monghidoro study [Italy], SILC study [China]) and 8 health-check studies (Japan,
      n = 1; China, n = 1; Taiwan, n = 4; Korea, n = 2). The prevalence of reflux
      esophagitis was 15.5% (Kalixanda), 11.8% (Loiano-Monghidoro), and 6.4% (SILC); it
      ranged from 3.4% to 8.5% in health-check studies in Japan, China, and Korea (n =
      4), but was higher (mean, 15.6%; range, 9.0%-24.6%; n = 4) in Taiwan. Hiatus
      hernia prevalence was 23.9% (Kalixanda), 43.0% (Loiano-Monghidoro), and 0.7%
      (SILC), and 0.8%-19.5% in health-check studies (n = 7). For endoscopically
      suspected esophageal metaplasia (ESEM), the prevalence was 10.3% (Kalixanda),
      3.6% (Loiano-Monghidoro), and 1.8% (SILC), and 0.0%-3.4% in health-check studies
      (n = 4). The prevalence of reflux esophagitis among individuals without symptom
      defined GERD was 12.1% (Kalixanda), 8.6% (Loiano-Monghidoro), 6.1% (SILC), and
      1.6%-22.8% (health-check studies; n = 6). For individuals without symptom-defined
      GERD, the prevalence of ESEM was 9.4% (Kalixanda), 2.8% (Loiano-Monghidoro), and
      1.8% (SILC). CONCLUSIONS: The prevalence of reflux esophagitis is higher in
      Sweden and Italy than in China, Korea, and Japan, but is within the range
      reported in Taiwan. Hiatus hernia and ESEM are generally more prevalent in Europe
      than in Asia. A considerable proportion of individuals without symptom-defined
      GERD has reflux esophagitis or ESEM.

PMID- 22401905
TI  - Intraneuronal Abeta accumulation and neurodegeneration: lessons from transgenic
      models.
AB  - AIMS: In the present review we summarize current knowledge on the concept of
      intraneuronal Abeta as a determinant for neuron loss and other pathological
      alterations in transgenic models for Alzheimer disease. MAIN METHODS: We discuss
      the use of transgenic mouse and non-vertebrate transgenic models accumulating
      intracellular Abeta peptides and their impact on the ongoing discussion. KEY
      FINDINGS: Intraneuronal Abeta accumulation in transgenic models is intimately
      linked to pathological alterations including neuron loss. One of the technical
      caveats for visualizing intraneuronal Abeta is the antibody used to unequivocally
      demonstrate its presence. Very often antibodies were used that recognize both
      Abeta and APP, leading to false positive results due to misinterpretation.
      SIGNIFICANCE: Whereas a clear relationship between intraneuronal Abeta
      accumulation and neuron loss is evident in transgenic mouse models it remains an
      unresolved issue whether the concept of intraneuronal Abeta can be integrated
      into the human pathology as well.

PMID- 22401906
TI  - Rapid determination of endogenous cytokinins in plant samples by combination of
      magnetic solid phase extraction with hydrophilic interaction chromatography
      tandem mass spectrometry.
AB  - A 2-acrylamido-2-methyl-1-propanesulfonic acid-co-ethylene glycol dimethacrylate
      (Fe3O4/SiO2/P(AMPS-co-EGDMA)) copolymer was prepared and used as a magnetic solid
      phase extraction (MSPE) medium for recovery of endogenous cytokinins (CKs) from
      plant extracts. This magnetic porous polymer was characterized by electron
      microscopy, nitrogen sorption experiments, elemental analysis and Fourier
      transformed infrared spectroscopy. It was demonstrated to have high extraction
      capacity toward CKs in plants due to its specificity, surface area and porous
      structure. Coupled with hydrophilic interaction chromatography-tandem mass
      spectrometry (HILIC-MS/MS), a rapid, simple, and effective MSPE-HILIC-MS/MS
      analytical method for the quantitative analysis of endogenous CKs in Oryza sativa
      (O. sativa) roots was successfully established. Good linearities were obtained
      for all CKs investigated with correlation coefficients (R2>0.9975. The results
      showed that LODs (S/N=3) were ranged from 0.18 to 3.65 pg mL-1. Reproducibility
      of the method was obtained with intra-day and inter-day relative standard
      deviations (RSDs) less than 16.1% and the recoveries in plant samples ranged from
      72.8% to 115.5%. Finally, the MSPE-HILIC-MS/MS method was applied to several
      plant samples, and the amounts of endogenous CKs in O. sativa roots, leaves and
      Arabidopsis thaliana (A. thaliana) were successfully determined.

PMID- 22401907
TI  - Glucagon-like peptide-1 of brainstem origin activates dorsomedial hypothalamic
      neurons in satiated rats.
AB  - A high number of neurons express c-fos in response to unlimited food intake in
      fasted rats in the ventral subdivision of the hypothalamic dorsomedial nucleus
      (DMHv). We report here, that in same conditions, limited food consumption failed
      to induce Fos expression in DMHv neurons suggesting that satiation should be one
      of the important signals that activate these neurons. The possible origin of
      fibers conducting satiation signals to the DMHv could be in the lower brainstem,
      especially glucagon-like peptide-1 (GLP-1)-containing neurons in the nucleus of
      the solitary tract (NTS). We demonstrate that GLP-1-immunoreactive fibers and
      fiber terminals topographically overlap with activated Fos-positive neurons in
      the DMHv in refed rats. Using immunocytochemistry and in situ hybridization
      histochemistry, we demonstrated GLP-1 receptors in Fos-expressing neurons of the
      DMH. Unilateral transections of ascending GLP-1-containing fibers from the NTS
      inside the pons in refed rats (unlimited food consumption) resulted in a dramatic
      decrease in the density of GLP-1 fibers and in the number of Fos-immunoreactive
      neurons in the DMHv, but only on the side of the transection. Contralateral to
      the transection, neither the GLP-1 fiber density nor the number of Fos-positive
      cells changed significantly. Meanwhile, the density of GLP-1 immunoreactivity was
      markedly accumulated in transected nerve fibers caudal to the cuts, as a
      consequence of the interruption of the ascending GLP-1 transport route. These
      findings suggest that the solitary-hypothalamic projections may represent the
      neuronal route through GLP-1 neurons of the NTS activate DMHv neurons via GLP-1
      receptors by conveying information on satiety.

PMID- 22401908
TI  - Larazotide acetate regulates epithelial tight junctions in vitro and in vivo.
AB  - Tight junctions (TJs) control paracellular permeability and apical-basolateral
      polarity of epithelial cells, and can be regulated by exogenous and endogenous
      stimuli. Dysregulated permeability is associated with pathological conditions,
      such as celiac disease and inflammatory bowel disease. Herein we studied the
      mechanism by which larazotide acetate, an 8-mer peptide and TJ regulator,
      inhibits the cellular changes elicited by gliadin fragments, AT-1002, and
      cytokines. Previously, we demonstrated that AT-1002, a 6-mer peptide derived from
      the Vibrio cholerae zonula occludens toxin ZOT, caused several biochemical
      changes in IEC6 and Caco-2 cells resulting in decreased transepithelial
      electrical resistance (TEER) and increased TJ permeability. In this study,
      larazotide acetate inhibited the redistribution and rearrangement of zonula
      occludens-1 (ZO-1) and actin caused by AT-1002 and gliadin fragments in Caco-2
      and IEC6 cells. Functionally, larazotide acetate inhibited the AT-1002-induced
      TEER reduction and TJ opening in Caco-2 cells. Additionally, larazotide acetate
      inhibited the translocation of a gliadin 13-mer peptide, which has been
      implicated in celiac disease, across Caco-2 cell monolayers. Further, apically
      applied larazotide acetate inhibited the increase in TJ permeability elicited by
      basolaterally applied cytokines. Finally, when tested in vivo in gliadin
      sensitized HLA-HCD4/DQ8 double transgenic mice, larazotide acetate inhibited
      gliadin-induced macrophage accumulation in the intestine and preserved normal TJ
      structure. Taken together, our data suggest that larazotide acetate inhibits
      changes elicited by AT-1002, gliadin, and cytokines in epithelial cells and
      preserves TJ structure and function in vitro and in vivo.

PMID- 22401909
TI  - LC-MS/MS with 2D mass mapping of skin secretions' peptides as a reliable tool for
      interspecies identification inside Rana esculenta complex.
AB  - Identification of species constituting Rana esculenta complex represents a
      certain problem as two parental species Rana ridibunda and Rana lessonae form
      their hybrid R. esculenta, while external signs and sizes of the members of this
      complex are intersected. However the composition of skin secretion consisting
      mainly of peptides is different for the species of the complex. LC-MS/MS is an
      ideal analytical tool for the quantitative and qualitative analysis of these
      peptides. The results covering elemental composition of these peptides, their
      levels in the secretion, as well as their belonging to a certain family of
      peptides may be visualized by means of 2D mass maps. The proposed approach proved
      itself to be a perspective tool for the reliable identification of all 3 species
      constituting R. esculenta complex. Easy distinguishing between the species may be
      achieved using 2D maps as fingerprints. Besides this approach may be used to
      study hybridogenesis and mechanisms of hemiclonal transfer of genetic
      information, when rapid and reliable identification of species involved in the
      process is required.

PMID- 22401910
TI  - Larazotide acetate promotes tight junction assembly in epithelial cells.
AB  - Tight junctions (TJ) control paracellular permeability and apical-basolateral
      polarity of epithelial cells. Dysregulated permeability is associated with
      pathological conditions, such as celiac disease and inflammatory bowel disease.
      TJ formation is dependent on E-cadherin-mediated cell-cell adhesion and actin
      rearrangement, and is regulated by the Rho family GTPase and aPKC signaling
      pathways. Larazotide acetate, an 8-mer peptide and TJ modulator, inhibits TJ
      disassembly and dysfunction caused by endogenous and exogenous stimuli in
      intestinal epithelial cells. Here, we examined the effect of larazotide acetate
      on de novo TJ assembly using 2 different model systems. In MDCK cells, larazotide
      acetate promoted TJ assembly in a calcium switch assay. Larazotide acetate also
      promoted actin rearrangement, and junctional distribution of zonula occludens-1
      (ZO-1), occludin, claudins, and E-cadherin. Larazotide acetate promoted TJ
      maturation and decreased paracellular permeability in "leaky" Caco-2 cells. Taken
      together, our data indicate that larazotide acetate enhances TJ assembly and
      barrier function by promoting actin rearrangement and redistribution of TJ and AJ
      proteins.

PMID- 22401911
TI  - Mucosal and parenteral vaccination against pneumonic pasteurellosis in cattle
      with a modified-live in-frame lktA deletion mutant of Mannheimia haemolytica.
AB  - A new temperature-conditional shuttle vector, pBB80C, was constructed and
      utilized to generate an in-frame deletion in the leukotoxin structural gene of
      Mannheimia haemolytica serotype 1. Culture supernatants from the mutant contained
      no detectable cytotoxicity to BL-3 lymphocyte targets, and contained a new
      protein with an approximate molecular weight of 66 kDa which was reactive to anti
      leukotoxin monoclonal antibody. No protein reactive to anti-LktA monoclonal
      antibody was detected at the molecular weight 100-105 kDa of native LktA. Calves
      vaccinated mucosally by top-dressing the live mutant onto feed, or parenterally
      by subcutaneous injection, were resistant to virulent challenge with the parent
      strain. Serologic antibody response, reduction in lung lesion, and reduction in
      pulmonary infectious load were greater among calves mucosally vaccinated than
      those which were vaccinated by injection.

PMID- 22401912
TI  - Oestrogen and breast cancer: results from the WHI trial.

PMID- 22401914
TI  - Semisynthesis and antimicrobial activity of novel guttiferone-A derivatives.
AB  - Six derivatives of guttiferone-A (LFQM-79, 80, 81, 82, 113 and 114) were
      synthesized and evaluated for their antimicrobial activity against the
      opportunistic or pathogenic fungi Candida albicans (ATCC 09548), Candida glabrata
      (ATCC 90030), Candida krusei (ATCC 6258), Candida parapsilosis (ATCC 69548),
      Candida tropicalis (ATCC 750), Cryptococcus neoformans (ATCC 90012), Trichophyton
      tonsurans, Microsporum gypseum and also against the opportunistic and pathogenic
      Gram-positive bacteria Staphylococcus aureus (ATCC 6538), Staphylococcus
      epidermidis (ATCC 12228), Bacillus cereus (ATCC 11778) and Gram-negative
      Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 9027), Salmonella
      typhimurium (ATCC 14028), Proteus mirabilis (ATCC 25933). The antimicrobial
      activities of derivatives were compared with guttiferone-A and they presented to
      be more potent than the original molecule and sometimes greater than standard
      drugs established in therapeutics. The current study showed that derivatives of
      guttiferone-A possess potent antimicrobial activity and are relatively non
      cytotoxic, which reveal these new molecules as promising new drug prototype
      candidates, with innovative structural pattern.

PMID- 22401913
TI  - Conjugated equine oestrogen and breast cancer incidence and mortality in
      postmenopausal women with hysterectomy: extended follow-up of the Women's Health
      Initiative randomised placebo-controlled trial.
AB  - BACKGROUND: By contrast with many observational studies, women in the Women's
      Health Initiative (WHI) trial who were randomly allocated to receive oestrogen
      alone had a lower incidence of invasive breast cancer than did those who received
      placebo. We aimed to assess the influence of oestrogen use on longer term breast
      cancer incidence and mortality in extended follow-up of this cohort. METHODS:
      Between 1993 and 1998, the WHI enrolled 10,739 postmenopausal women from 40 US
      clinical centres into a randomised, double-masked, placebo-controlled trial.
      Women aged 50-79 years who had undergone hysterectomy and had expected 3-year
      survival and mammography clearance were randomly allocated by a computerised,
      permuted block algorithm, stratified by age group and centre, to receive oral
      conjugated equine oestrogen (0.625 mg per day; n=5310) or matched placebo
      (n=5429). The trial intervention was terminated early on Feb 29, 2004, because of
      an adverse effect on stroke. Follow-up continued until planned termination (March
      31, 2005). Consent was sought for extended surveillance from the 9786 living
      participants in active follow-up, of whom 7645 agreed. Using data from this
      extended follow-up (to Aug 14, 2009), we assessed long-term effects of oestrogen
      use on invasive breast cancer incidence, tumour characteristics, and mortality.
      We used Cox regression models to estimate hazard ratios (HRs) in the intention-to
      treat population. This study is registered with ClinicalTrials.gov, number
      NCT00000611. FINDINGS: After a median follow-up of 11.8 years (IQR 9.1-12.9), the
      use of oestrogen for a median of 5.9 years (2.5-7.3) was associated with lower
      incidence of invasive breast cancer (151 cases, 0.27% per year) compared with
      placebo (199 cases, 0.35% per year; HR 0.77, 95% CI 0.62-0.95; p=0.02) with no
      difference (p=0.76) between intervention phase (0.79, 0.61-1.02) and post
      intervention phase effects (0.75, 0.51-1.09). In subgroup analyses, we noted
      breast cancer risk reduction with oestrogen use was concentrated in women without
      benign breast disease (p=0.01) or a family history of breast cancer (p=0.02). In
      the oestrogen group, fewer women died from breast cancer (six deaths, 0.009% per
      year) compared with controls (16 deaths, 0.024% per year; HR 0.37, 95% CI 0.13
      0.91; p=0.03). Fewer women in the oestrogen group died from any cause after a
      breast cancer diagnosis (30 deaths, 0.046% per year) than did controls (50
      deaths, 0.076%; HR 0.62, 95% CI 0.39-0.97; p=0.04). INTERPRETATION: Our findings
      provide reassurance for women with hysterectomy seeking relief of climacteric
      symptoms in terms of the effects of oestrogen use for about 5 years on breast
      cancer incidence and mortality. However, our data do not support use of oestrogen
      for breast cancer risk reduction because any noted benefit probably does not
      apply to populations at increased risk of such cancer. FUNDING: US National
      Heart, Lung, and Blood Institute; Wyeth.

PMID- 22401915
TI  - Bacterial quorum sensing molecule induces chemotaxis of human neutrophils via
      induction of p38 and leukocyte specific protein 1 (LSP1).
AB  - When bacteria colonize surfaces, they socialize and form biofilms. This process
      is well regulated and relies on the communication among the bacteria via so
      called "quorum sensing molecules". Among those, N-(3-oxododecanoyl)-L-homoserine
      lactone (AHL-12), generated by Pseudomonas aeruginosa and other Gram-negative
      bacteria, activates not only bacteria but also interacts with mammalian cells.
      Among others, it activates phagocytic cells and - as we had shown previously - it
      is chemotactic for human polymorphonuclear neutrophils (PMN) in vitro. In the
      present study, we analyzed the signalling pathway of AHL-12 in PMN. We focused on
      the mitogen activated protein (MAP) kinase p38, because SB203580, an inhibitor of
      p38, prevented the AHL-12 induced chemotaxis. We found that in response to AHL
      12, p38 was phosphorylated within minutes, as was its downstream target, the
      MAPKAP-Kinase-2 (MK2). In PMN, the major substrate of MK2 is the leukocyte
      specific protein 1 (LSP1), which binds to F-actin and participates directly in
      actin polymerization and cell migration. In response to AHL-12, LSP1 was
      phosphorylated and co-localized with F-actin in polarized PMN, suggesting that
      AHL-12-induced migration depended on p38 and LSP1 activation.

PMID- 22401917
TI  - Australasian Gastrointestinal Trials Group (AGITG) contouring atlas and planning
      guidelines for intensity-modulated radiotherapy in anal cancer.
AB  - PURPOSE: To develop a high-resolution target volume atlas with intensity
      modulated radiotherapy (IMRT) planning guidelines for the conformal treatment of
      anal cancer. METHODS AND MATERIALS: A draft contouring atlas and planning
      guidelines for anal cancer IMRT were prepared at the Australasian
      Gastrointestinal Trials Group (AGITG) annual meeting in September 2010. An expert
      panel of radiation oncologists contoured an anal cancer case to generate
      discussion on recommendations regarding target definition for gross disease,
      elective nodal volumes, and organs at risk (OARs). Clinical target volume (CTV)
      and planning target volume (PTV) margins, dose fractionation, and other IMRT
      specific issues were also addressed. A steering committee produced the final
      consensus guidelines. RESULTS: Detailed contouring and planning guidelines and a
      high-resolution atlas are provided. Gross tumor and elective target volumes are
      described and pictorially depicted. All elective regions should be routinely
      contoured for all disease stages, with the possible exception of the inguinal and
      high pelvic nodes for select, early-stage T1N0. A 20-mm CTV margin for the
      primary, 10- to 20-mm CTV margin for involved nodes and a 7-mm CTV margin for the
      elective pelvic nodal groups are recommended, while respecting anatomical
      boundaries. A 5- to 10-mm PTV margin is suggested. When using a simultaneous
      integrated boost technique, a dose of 54 Gy in 30 fractions to gross disease and
      45 Gy to elective nodes with chemotherapy is appropriate. Guidelines are provided
      for OAR delineation. CONCLUSION: These consensus planning guidelines and high
      resolution atlas complement the existing Radiation Therapy Oncology Group (RTOG)
      elective nodal ano-rectal atlas and provide additional anatomic, clinical, and
      technical instructions to guide radiation oncologists in the planning and
      delivery of IMRT for anal cancer.

PMID- 22401918
TI  - Outcome of patients with pilocytic astrocytoma and leptomeningeal dissemination.
AB  - PURPOSE: To determine the patient, tumor, and treatment characteristics of
      patients with pilocytic astrocytoma (PA) and leptomeningeal dissemination (LMD).
      METHODS AND MATERIALS: A PubMed search of English-language studies pertaining to
      PA with LMD was performed using a combination of keywords that included juvenile
      pilocytic astrocytoma, low-grade astrocytoma, low-grade glioma, leptomeningeal
      dissemination, neuraxis spread, and radiotherapy. We found 26 studies with 58
      patients between 1976 and 2005 that met these criteria. RESULTS: The median
      survival for PA patients with LMD was 65 months. The 1-, 2-, and 5-year overall
      survival (OS) rate after the diagnosis of LMD was 81.1%, 75.7%, and 55.5%. The 1
      , 2-, and 5-year progression-free survival (PFS) rate after the diagnosis of LMD
      was 69.3%, 66.5%, and 34.6%, respectively. Age, gender, primary site location,
      timing of LMD presentation (synchronous vs. metachronous), and LMD location did
      not significantly influence OS or PFS. No statistically significant difference
      was found in OS or PFS between the chemotherapy and radiotherapy groups.
      Likewise, no difference was found in OS or PFS according to the use of
      craniospinal irradiation vs. less extensive RT fields. CONCLUSIONS: Approximately
      one-half of PA patients were alive 5 years after the diagnosis of LMD. Both
      chemotherapy and radiotherapy have efficacy against LMD. Although the use of
      craniospinal irradiation did not have an effect on PFS, the patient numbers were
      small and a larger number treated with craniospinal irradiation is needed to
      determine its efficacy.

PMID- 22401916
TI  - Bladder preservation for localized muscle-invasive bladder cancer: the survival
      impact of local utilization rates of definitive radiotherapy.
AB  - PURPOSE: This study examines the management and outcomes of muscle-invasive
      bladder cancer in the United States. METHODS AND MATERIALS: Patients with muscle
      invasive bladder cancer diagnosed between 1988 and 2006 were identified in the
      Surveillance, Epidemiology, and End Results (SEER) database. Patients were
      classified according to three mutually exclusive treatment categories based on
      the primary initial treatment: no local management, radiotherapy, or surgery.
      Overall survival was assessed with Kaplan-Meier analysis and Cox models based on
      multiple factors including treatment utilization patterns. RESULTS: The study
      population consisted of 26,851 patients. Age, sex, race, tumor grade, histology,
      and geographic location were associated with differences in treatment (all p <
      0.01). Patients receiving definitive radiotherapy tended to be older and have
      less differentiated tumors than patients undergoing surgery (RT, median age 78
      years old and 90.6% grade 3/4 tumors; surgery, median age 71 years old and 77.1%
      grade 3/4 tumors). No large shifts in treatment were seen over time, with most
      patients managed with surgical resection (86.3% for overall study population).
      Significant survival differences were observed according to initial treatment:
      median survival, 14 months with no definitive local treatment; 17 months with
      radiotherapy; and 43 months for surgery. On multivariate analysis, differences in
      local utilization rates of definitive radiotherapy did not demonstrate a
      significant effect on overall survival (hazard ratio, 1.002; 95% confidence
      interval, 0.999-1.005). CONCLUSIONS: Multiple factors influence the initial
      treatment strategy for muscle-invasive bladder cancer, but definitive
      radiotherapy continues to be used infrequently. Although patients who undergo
      surgery fare better, a multivariable model that accounted for patient and tumor
      characteristics found no survival detriment to the utilization of definitive
      radiotherapy. These results support continued research into bladder preservation
      strategies and suggest that definitive radiotherapy represents a viable initial
      treatment strategy for those who wish to attempt to preserve their native
      bladder.

PMID- 22401919
TI  - Contouring variability of the penile bulb on CT images: quantitative assessment
      using a generalized concordance index.
AB  - PURPOSE: Within a multicenter study (DUE-01) focused on the search of predictors
      of erectile dysfunction and urinary toxicity after radiotherapy for prostate
      cancer, a dummy run exercise on penile bulb (PB) contouring on computed
      tomography (CT) images was carried out. The aim of this study was to
      quantitatively assess interobserver contouring variability by the application of
      the generalized DICE index. METHODS AND MATERIALS: Fifteen physicians from
      different Institutes drew the PB on CT images of 10 patients. The spread of DICE
      values was used to objectively select those observers who significantly disagreed
      with the others. The analyses were performed with a dedicated module in the VODCA
      software package. RESULTS: DICE values were found to significantly change among
      observers and patients. The mean DICE value was 0.67, ranging between 0.43 and
      0.80. The statistics of DICE coefficients identified 4 of 15 observers who
      systematically showed a value below the average (p value range, 0.013 - 0.059):
      Mean DICE values were 0.62 for the 4 "bad" observers compared to 0.69 of the 11
      "good" observers. For all bad observers, the main cause of the disagreement was
      identified. Average DICE values were significantly worse from the average in 2 of
      10 patients (0.60 vs. 0.70, p < 0.05) because of the limited visibility of the
      PB. Excluding the bad observers and the "bad" patients," the mean DICE value
      increased from 0.67 to 0.70; interobserver variability, expressed in terms of
      standard deviation of DICE spread, was also reduced. CONCLUSIONS: The obtained
      values of DICE around 0.7 shows an acceptable agreement, considered the small
      dimension of the PB. Additional strategies to improve this agreement are under
      consideration and include an additional tutorial of the so-called bad observers
      with a recontouring procedure, or the recontouring by a single observer of the PB
      for all patients included in the DUE-01 study.

PMID- 22401920
TI  - Impact of immobilization on intrafraction motion for spine stereotactic body
      radiotherapy using cone beam computed tomography.
AB  - PURPOSE: Spine stereotactic body radiotherapy (SBRT) involves tight planning
      margins and steep dose gradients to the surrounding organs at risk (OAR). This
      study aimed to assess intrafraction motion using cone beam computed tomography
      (CBCT) for spine SBRT patients treated using three immobilization devices.
      METHODS AND MATERIALS: Setup accuracy using CBCT was retrospectively analyzed for
      102 treated spinal metastases in 84 patients. Thoracic and lumbar spine patients
      were immobilized with either an evacuated cushion (EC, n = 24) or a semirigid
      vacuum body fixation (BF, n = 60). For cases treated at cervical/upper thoracic
      (thoracic [T]1-T3) vertebrae, a thermoplastic S-frame (SF) mask (n = 18) was
      used. Patient setup was corrected by using bony anatomy image registration and
      couch translations only (no rotation corrections) with shifts confirmed on
      verification CBCTs. Repeat imaging was performed mid- and post-treatment. Patient
      translational and rotational positioning data were recorded to calculate means,
      standard deviations (SD), and corresponding margins +/- 2 SD for residual setup
      errors and intrafraction motion. RESULTS: A total of 355 localizations, 333
      verifications, and 248 mid- and 280 post-treatment CBCTs were analyzed. Residual
      translations and rotations after couch corrections (verification scans) were
      similar for all immobilization systems, with SDs of 0.6 to 0.9 mm in any
      direction and 0.9 degrees  to 1.6 degrees , respectively. Margins to encompass
      residual setup errors after couch corrections were within 2 mm. Including
      intrafraction motion, as measured on post-treatment CBCTs, SDs for total setup
      error in the left-right, cranial-caudal, and anterior-posterior directions were
      1.3, 1.2, and 1.0 mm for EC; 0.9, 0.7, and 0.9 mm for BF; and 1.3, 0.9, and 1.1
      mm for SF, respectively. The calculated margins required to encompass total setup
      error increased to 3 mm for EC and SF and remained within 2 mm for BF.
      CONCLUSION: Following image guidance, residual setup errors for spine SBRT were
      similar across three immobilization systems. The BF device resulted in the least
      amount of intrafraction motion, and based on this device, we justify a 2-mm
      margin for the planning OAR and target volume.

PMID- 22401921
TI  - Apolipoprotein e genotype-dependent paradoxical short-term effects of (56)fe
      irradiation on the brain.
AB  - PURPOSE: In humans, apolipoprotein E (apoE) is encoded by three major alleles
      (epsilon2, epsilon3, and epsilon4) and, compared to apoE3, apoE4 increases the
      risk of developing Alzheimer disease and cognitive impairments following various
      environmental challenges. Exposure to irradiation, including that of (56)Fe,
      during space missions poses a significant risk to the central nervous system, and
      apoE isoform might modulate this risk. METHODS AND MATERIALS: We investigated
      whether apoE isoform modulates hippocampus-dependent cognitive performance
      starting 2 weeks after (56)Fe irradiation. Changes in reactive oxygen species
      (ROS) can affect cognition and are induced by irradiation. Therefore, after
      cognitive testing, we assessed hippocampal ROS levels in ex vivo brain slices,
      using the ROS-sensitive fluorescent probe, dihydroethidium (DHE). Brain levels of
      3-nitrotyrosine (3-NT), CuZn superoxide dismutase (CuZnSOD), extracellular SOD,
      and apoE were assessed using Western blotting analysis. RESULTS: In the water
      maze, spatial memory retention was impaired by irradiation in apoE2 and apoE4
      mice but enhanced by irradiation in apoE3 mice. Irradiation reduced DHE-oxidation
      levels in the enclosed blade of the dentate gyrus and levels of 3-NT and CuZnSOD
      in apoE2 but not apoE3 or apoE4 mice. Finally, irradiation increased apoE levels
      in apoE3 but not apoE2 or apoE4 mice. CONCLUSIONS: The short-term effects of
      (56)Fe irradiation on hippocampal ROS levels and hippocampus-dependent spatial
      memory retention are apoE isoform-dependent.

PMID- 22401922
TI  - Upfront androgen deprivation therapy with salvage radiation may improve
      biochemical outcomes in prostate cancer patients with post-prostatectomy rising
      PSA.
AB  - PURPOSE: The addition of androgen deprivation therapy (ADT) to definitive
      external beam radiation therapy (RT) improves outcomes in higher-risk prostate
      cancer patients. However, the benefit of ADT with salvage RT in post
      prostatectomy patients is not clearly established. Our study compares biochemical
      outcomes in post-prostatectomy patients who received salvage RT with or without
      concurrent ADT. METHODS AND MATERIALS: Of nearly 2,000 post-prostatectomy
      patients, we reviewed the medical records of 191 patients who received salvage RT
      at the University of Pennsylvania between 1987 and 2007. Follow-up data were
      obtained by chart review and electronic polling of the institutional laboratory
      database and Social Security Death Index. Biochemical failure after salvage RT
      was defined as a prostate-specific antigen of 2.0 ng/mL above the post-RT nadir
      or the initiation of ADT after completion of salvage RT. RESULTS: One hundred
      twenty-nine patients received salvage RT alone, and 62 patients received combined
      ADT and salvage RT. Median follow-up was 5.4 years. Patients who received
      combined ADT and salvage RT were younger, had higher pathologic Gleason scores,
      and higher rates of seminal vesicle invasion, lymph node involvement, and pelvic
      nodal irradiation compared with patients who received salvage RT alone. Patients
      who received combined therapy had improved biochemical progression-free survival
      (bPFS) compared with patients who received RT alone (p = 0.048). For patients
      with pathologic Gleason scores <=7, combined RT and ADT resulted in significantly
      improved bPFS compared to RT alone (p = 0.013). CONCLUSIONS: These results
      suggest that initiating ADT during salvage RT in the post-prostatectomy setting
      may improve bPFS compared with salvage RT alone. However, prospective randomized
      data are necessary to definitively determine whether hormonal manipulation should
      be used with salvage RT. Furthermore, the optimal nature and duration of ADT and
      the patient subgroups in which ADT could provide the most benefit remain open
      questions.

PMID- 22401923
TI  - An innovative tool for intraoperative electron beam radiotherapy simulation and
      planning: description and initial evaluation by radiation oncologists.
AB  - PURPOSE: Intraoperative electron beam radiation therapy (IOERT) involves a
      modified strategy of conventional radiation therapy and surgery. The lack of
      specific planning tools limits the spread of this technique. The purpose of the
      present study is to describe a new simulation and planning tool and its initial
      evaluation by clinical users. METHODS AND MATERIALS: The tool works on a
      preoperative computed tomography scan. A physician contours regions to be treated
      and protected and simulates applicator positioning, calculating isodoses and the
      corresponding dose--volume histograms depending on the selected electron energy.
      Three radiation oncologists evaluated data from 15 IOERT patients, including
      different tumor locations. Segmentation masks, applicator positions, and
      treatment parameters were compared. RESULTS: High parameter agreement was found
      in the following cases: three breast and three rectal cancer, retroperitoneal
      sarcoma, and rectal and ovary monotopic recurrences. All radiation oncologists
      performed similar segmentations of tumors and high-risk areas. The average
      applicator position difference was 1.2 +/- 0.95 cm. The remaining cancer sites
      showed higher deviations because of differences in the criteria for segmenting
      high-risk areas (one rectal, one pancreas) and different surgical access
      simulated (two rectal, one Ewing sarcoma). CONCLUSIONS: The results show that
      this new tool can be used to simulate IOERT cases involving different anatomic
      locations, and that preplanning has to be carried out with specialized surgical
      input.

PMID- 22401924
TI  - Image-based dynamic multileaf collimator tracking of moving targets during
      intensity-modulated arc therapy.
AB  - PURPOSE: Intensity-modulated arc therapy (IMAT) enables efficient and highly
      conformal dose delivery. However, intrafraction motion may compromise the
      delivered target dose distribution. Dynamic multileaf collimator (DMLC) tracking
      can potentially mitigate the impact of target motion on the dose. The purpose of
      this study was to use a single kV imager for DMLC tracking during IMAT and to
      investigate the ability of this tracking to maintain the dose distribution.
      METHODS: A motion phantom carrying a two-dimensional (2D) ion chamber array and
      buildup material with an embedded gold marker reproduced eight representative
      tumor trajectories (four lung tumors, four prostate). For each trajectory, a low
      and high IMAT plan were delivered with and without DMLC tracking. The three
      dimensional (3D) real-time target position signal for tracking was provided by
      fluoroscopic kV images acquired immediately before and during treatment. For each
      image, the 3D position of the embedded marker was estimated from the imaged 2D
      position by a probability-based method. The MLC leaves were continuously refitted
      to the estimated 3D position. For lung, prediction was used to compensate for the
      tracking latency. The delivered 2D dose distributions were measured with the ion
      chamber array and compared with a reference dose distribution delivered without
      target motion using a 3%/3 mm gamma-test. RESULTS: For lung tumor motion,
      tracking reduced the mean gamma-failure rate from 38% to 0.7% for low-modulation
      IMAT plans and from 44% to 2.8% for high-modulation plans. For prostate, the
      gamma-failure rate reduction was from 19% to 0% (low modulation) and from 20% to
      2.7% (high modulation). The dominant contributor to the residual gamma-failures
      during tracking was target localization errors for most lung cases and leaf
      fitting errors for most prostate cases. CONCLUSION: Image-based tracking for IMAT
      was demonstrated for the first time. The tracking greatly improved the dose
      distributions to moving targets.

PMID- 22401925
TI  - Localization of a portion of an endorectal balloon for prostate image-guided
      radiation therapy using cone-beam tomosynthesis: a feasibility study.
AB  - PURPOSE: To assess the feasibility of using cone-beam tomosynthesis (CBTS) to
      localize the air-tissue interface for the application of prostate image-guided
      radiation therapy using an endorectal balloon for immobilization and
      localization. METHODS AND MATERIALS: A Feldkamp-David-Kress-based CBTS
      reconstruction was applied to selected sets of cone-beam computed tomography
      (CBCT) projection data to simulate volumetric imaging achievable from
      tomosynthesis for a limited range of scan angles. Projection data were calculated
      from planning CT images of 10 prostate cancer patients treated with an endorectal
      balloon, as were experimental CBCT projections for a pelvic phantom in two
      patients. More than 50 points at the air-tissue interface were objectively
      identified by an intensity-based interface-finding algorithm. Using three
      dimensional point sets extracted from CBTS images compared with points extracted
      from corresponding CBCT images, the relative shift resulting from a reduced scan
      angle was determined. Because the CBCT and CBTS images were generated from the
      same projection data set, shift identified was presumed to be due to distortions
      introduced by the tomosynthesis technique. RESULTS: Scans of >=60 degrees  were
      shown to be able to localize an air-tissue interface near the isocenter with
      accuracy on the order of a millimeter. The accuracy was quantified in terms of
      the mean discrepancy as a function of reconstruction angle. CONCLUSION: This work
      provides an understanding of the effect of scan angle used in localization of a
      portion of an endorectal balloon by means of CBTS. CBTS with relatively small
      scan angles is capable of accurately localizing an extended interface near the
      isocenter and may provide clinically relevant measurements to guide IGRT
      treatments while reducing imaging radiation to the patient.

PMID- 22401926
TI  - The chemistry/biology interface.

PMID- 22401927
TI  - Can plasma DNA monitoring be employed in personalized chemotherapy for patients
      with advanced lung cancer?
AB  - Personalized chemotherapy is the ideal treatment usually chosen to help improve
      the survival chances of patients with advanced lung cancer. However, there is no
      short-term evaluation protocol for predicting the efficacy of the therapy. The
      aim of this study was to determine the value of using plasma DNA to monitor
      chemotherapeutic efficacy and to select most appropriate chemotherapeutic regimen
      for patients with advanced lung cancer. Eighty-eight lung cancer patients and 200
      healthy controls were included in this study. Plasma DNA was extracted from
      plasma samples with internal controls by using the BILATEST DNA Kit. The quantity
      of plasma DNA was determined by using duplex real-time quantitative PCR. After
      first-line chemotherapy, plasma DNA levels of partial response patients were
      significantly different from those of stable disease patients or progressive
      disease patients, but with no statistical difference from healthy controls
      (P=0.014, P<0.001 and P=0.418, respectively). Survival analysis showed a
      statistically better survival time in patients who had lower levels of plasma DNA
      after the third cycle chemotherapy (P=0.031). In this study, the correlation of
      the kinetics of DNA concentrations with chemotherapeutic efficacy during the
      whole therapy was also observed. The quantification of plasma DNA is a sensitive
      indicator of chemotherapeutic efficacy in advanced lung cancer patients, and it
      can be useful in predicting response to therapy and guiding medication.

PMID- 22401928
TI  - Prognostic factors for therapy-related acute myeloid leukaemia (t-AML)--a single
      centre experience.
AB  - Prognostic parameters for treatment outcome in 42 consecutive patients with t-AML
      diagnosed and treated in a single centre between 2000-2010 (mean age: 56.07
      years, range: 23-84; 30 females) were evaluated retrospectively/prospectively.
      Antecedent malignancy occurred in 37 patients (88.15%): 28 solid cancers (breast,
      n=14), nine haematological. History of previous chemotherapy (CT), radiotherapy
      (RT) alone and combined CT/RT was present in 42.9%, 6.19% and 30.1% patients,
      respectively. Primary disease was active in 11 patients (six relapsed or
      metastatic cancers; five autoimmune diseases). Myelodysplastic syndrome preceded
      t-AML in 29% of patients. Median latency period from prior CT/RT was 54.62 months
      (range: 6-243). Median WBC count was 27.23 * 109/L, platelet count 62.29 * 109/L,
      haemoglobin level 87.83 g/L, peripheral blood and bone marrow blast percentage
      30.7% and 66.7% respectively, serum LDH 1216 U/L. Aberrant expression of B or T
      lymphoid markers was registered in seven out of 39 and six out of 39 patients,
      respectively. Aberrant karyotype was detected in 24 out of 33 (72.7%) of eligible
      patients: favourable: 15.2%, intermediate: 42.4% and unfavourable: 42.4%. Eastern
      Cooperative Oncology Group (ECOG) performance status greater or equal to 2 and
      Haematopoietic Cell Transplantation Specific Comorbidity Index (HCT-CI) greater
      or equal to 3 exhibited 83.3% and 76.2% patients, respectively. Intensive
      induction CT for t-AML was administered in 24 patients. The median follow-up and
      the median overall survival (OS) for the whole cohort were 2 months and 5.94
      months (range: 0.5-34), respectively. In 10 patients (23.8%) achieving complete
      remission (CR), median disease free survival (DFS) was 11.8 months (range: 4-32).
      Only CD19 expression, pretreatment karyotype, ECOG PS, HCT-CI and activity of
      primary disease had impact on OS (P<0.05).

PMID- 22401929
TI  - The prognostic significance of chemokine receptor CXCR3 expression in colorectal
      carcinoma.
AB  - The expression of chemokine receptor CXCR3 has been associated with tumor
      dissemination and poor prognosis in breast cancer patients. However, it is still
      unclear whether CXCR3 can be used as an independent molecular marker for
      predicting the prognosis of colonrectal carcinoma (CRC) patients. In this study,
      we found that the relative level of CXCR3 mRNA expression in primary colorectal
      cancer tissues was significantly higher than that in corresponding non-tumor
      colon tissues. CXCR3 protein expression was also detected in 98 of 112 primary
      CRC patients. Thus, CXCR3 might play a vital role in the progression of
      colorectal cancer. By analyzing the correlation between clinicopathological
      factors of patients and expression of CXCR3 protein, we showed that high level of
      CXCR3 protein expression was significantly associated with tumor differentiation,
      tumor size, lymph node metastasis, distant metastasis, and Dukes' classification,
      but not with other factors of CRC patients including gender, age, tumor location
      and tumor invasion. Furthermore, patients with high CXCR3 expression showed
      poorer overall survival than those with low CXCR3 expression. Univariate and
      multivariate analysis indicated that the status of CXCR3 protein expression might
      be an independent prognostic marker for CRC patients. Therefore, CXCR3 is an
      indicator of a poor prognosis and a promising target for cancer therapy in
      colorectal cancer.

PMID- 22401930
TI  - B-type natriuretic peptide in rheumatic diseases: a cardiac biomarker or a
      sophisticated acute phase reactant?
AB  - Natriuretic peptides (NP) are secreted by cardiomyocytes and are reliable markers
      of cardiac dysfunction and cardiovascular risk by reflecting myocardial stress
      due to various etiologies. Clinical and occult heart involvement is frequently
      observed in patients with rheumatic diseases and is associated with increased
      morbidity and mortality. Cardiac disease in autoimmune disorders encompasses
      different pathophysiological mechanisms including inflammation and involving
      either the myocardium or the coronary/pulmonary vessels. Although the major
      trigger for the synthesis and release of NP is myocardial strain, there is also
      some support for the concept that inflammation stimulates the neurohormonal
      system of the heart leading to increased production of NP. Recent studies have
      focused on the association of NP and inflammation in the context of rheumatic
      diseases, suggesting that up-regulation of neurohormonal axis in these conditions
      is linked with inflammation. Additionally the NP have a well-documented role in
      the diagnostic work-up of patients with connective tissue disease who are at
      increased risk of developing pulmonary hypertension, as the right ventricular
      overload results in increased NP synthesis and release. However the precise role
      of NP in the assessment and the management of cardiovascular risk in patients
      with rheumatic diseases is yet to be established. In the current article we
      discuss the pathophysiologic mechanisms involved in enhanced NP expression in
      patients with rheumatic disorders and their potential clinical implication in
      daily practice.

PMID- 22401931
TI  - Ras family of small GTPases in immunity and inflammation.
AB  - The Ras superfamily of small GTPases is a group of more than 150 small G
      proteins, all of which share some degree of homology to the founding member Ras.
      These small GTPases function as molecular switches within cells, impacting nearly
      all cellular processes. The Ras superfamily can be further divided into several
      smaller subfamilies, with those proteins that most closely resemble Ras belonging
      to the Ras subfamily. While heavily studied within the field of cancer biology,
      the Ras family of proteins also plays cardinal roles in immunity and
      inflammation. Here we review the roles of these molecular switches in regulating
      immune cell homeostasis and functions.

PMID- 22401932
TI  - SIRT1 signaling as potential modulator of skeletal muscle diseases.
AB  - Skeletal muscle diseases heavily impair the strength and the movement of
      patients. Muscles loose their adaptive capacity, undergoing atrophy or wasting,
      due to a number of pathological insults. Metabolic changes, such as those
      occurring during aging, contribute to the progressive reduction of myofiber size
      and decline of skeletal muscle performance that is typically observed in the
      elderly. The nicotinamide adenine dinucleotide (NAD)-dependent deacetylase SIRT1
      has been involved in the protection against metabolic disorders, against cancers
      and in the enhancement of life span. Here we discuss the current evidence placing
      SIRT1 at the crossroad between energy homeostasis, fiber strength, and
      regeneration from damage in the skeletal muscle. Furthermore, we underline how
      cell type specific targeting of SIRT1 could be beneficial in the treatment of
      skeletal muscle diseases.

PMID- 22401933
TI  - Vestibular evoked myogenic potentials in multiple sclerosis.

PMID- 22401934
TI  - Externally cued inphase bimanual training enhances preparatory premotor activity.
AB  - OBJECTIVE: Previous studies have demonstrated that cortical potentials
      representing motor preparation for visually-cued movements are enhanced following
      a single session of visually-cued bimanual movement training (BMT). The
      neuroanatomical sources that contribute to these rapid training-induced
      adaptations were unclear. To address this, we compared cortical potentials
      associated with motor preparation for visually-cued (movement-related potential,
      MRP) and self-paced (Bereitschaftspotential, BP) movements and investigated
      adaptations of these following BMT. METHODS: EEG recorded the cued MRP and self
      paced BP during two experiments. In experiment one, pre and post self-paced
      unimanual trials were interspersed with cued inphase BMT. In experiment two, self
      paced and visually-cued movement trials were performed to assess the differences
      between and the contributing neural sources to the cued MRP and self-paced BP.
      RESULTS: Inphase BMT does not affect the early BP. Source localization analysis
      revealed that the preparatory portion of the cued MRP and self-paced BP are
      generated by the lateral premotor cortex and the supplementary motor area,
      respectively. CONCLUSIONS: The early cued MRP and self-paced BP have unique
      cortical generators and are independently modulated by specific training types.
      SIGNIFICANCE: These novel findings have implications for interpreting rapid,
      single-session, training adaptations previously observed. These cortical
      potentials may also be useful measurement tools to gauge within-session cortical
      modulations in response to specific modes of rehabilitative training in the
      stroke population.

PMID- 22401935
TI  - [Recurrent ingestion of magnets in children: importance of early identification].

PMID- 22401936
TI  - Is medroxyprogesterone safe in women with long QT syndrome?

PMID- 22401937
TI  - Inhibition of inflammations and macrophage activation by ginsenoside-Re isolated
      from Korean ginseng (Panax ginseng C.A. Meyer).
AB  - This study was undertaken to evaluate the effect of ginsenoside-Re (Gin-Re)
      isolated from roots of Panax ginseng on carrageenan-induced paw and TPA-induced
      skin inflammations in experimental mice. Moreover, to confirm further the anti
      inflammatory activities of Gin-Re, LPS-induced macrophage activation model was
      also used. Exposure of TPA on the ear of BALB/c mice caused a marked increase in
      both ear thickness and skin water content. Gin-Re caused significant decrease in
      ear thickness and subsequently reduced the water content compared to only TPA
      treated group (p<0.05). Furthermore, histological analysis clearly confirmed that
      Gin-Re inhibited the inflammatory responses of skin inflammation in animal model.
      Gin-Re was responded well in inhibiting paw thickness, MDA level and also NO
      level in carrageenan induced paw edema model compared to only carrageenan treated
      group. Treatment with Gin-Re inhibited secretion levels of inflammatory mediators
      such as tumor necrosis factor alpha (TNF alpha), and interleukin-1beta (IL-1beta)
      in LPS-stimulated murine macrophage Raw 264.7 cells. Despite the fact that Gin-Re
      has weaker anti-inflammatory potential than the positive controls, indomethacin
      and hydrocortisone, in the entire group tested, quite effective anti-inflammatory
      activity was shown by Gin-Re, which could be helpful to develop medicinal
      preparations for various inflammatory diseases.

PMID- 22401938
TI  - Radioactivity measurements of 177Lu, 111In and 123I by different absolute
      methods.
AB  - The activities of (177)Lu, (111)In and (123)I solutions have been absolutely
      determined using three different measurement methods. (177)Lu solution was
      standardized using the 4pibeta(PC)-gamma(NaI) coincidence and 4pibeta(LS)
      gamma(NaI) live-timed anticoincidence methods. For the (111)In and (123)I
      solutions, besides these two mentioned methods, the coincidence sum-peak method
      was also applied. The measured activities results using these different methods
      are consistent within the evaluated experimental uncertainties demonstrating the
      equivalence of these methods. As an additional contribution to nuclear data, the
      half-lives have been determined using a well type IG12 ionization chamber.

PMID- 22401939
TI  - Gamma-ray emission probabilities in the decay of (177m)Lu.
AB  - gamma-Ray emission probabilities from the decay of the long-lived
      (T(1/2)=160.44d) isomeric state in (177m)Lu were measured with planar (LEPS) and
      coaxial Ge detectors. The isomer gamma-ray and beta(-)-decay branching
      intensities were also determined. Measurements were carried out at low absolute
      efficiencies in order to minimize coincidence summing losses. The results are
      compared with the previous measurements.

PMID- 22401940
TI  - Applicability of natural colourless topaz as a high-energy beam dosimeter.
AB  - Thermoluminescence characteristics of colourless topaz collected from Pakistan
      were studied. The objective of this study was to design and develop a TL
      dosimeter for high-energy beams. Samples were irradiated with (60)Co, (137)Cs and
      linear accelerator (6 MV, 15 MV). Glow curves of the chips revealed four trapping
      levels at temperature ranges 71-82  degrees C (Peak 1), 173-185  degrees C (Peak
      2), 197-210  degrees C (Peak 3) and 225-260  degrees C (Peak 4). Peak 4 is stable
      and rose linearly with increase of exposure levels. The TL response vs. exposure
      showed linear behaviour between 1 and 10(2) Gy. Initial fading is rapid in first
      24 h and becomes 8% in next 19 days. The variation in response of the last 20th
      cycle with respect to the 1st cycle was found to be 4% with a maximum variation
      of 15% within all data points. The thermoluminescence response was observed to be
      higher at low energy. The chips remained mechanically intact during handling in
      all experiments. Topaz chips can effectively and efficiently be used as a TLD for
      high-energy beams.

PMID- 22401941
TI  - Improvement of software coincidence counting system for standardisation of EC
      beta(+) radionuclides.
AB  - Since 2000 the software coincidence counting (SCC) system has been used for
      activity standardisation of about 15 radionuclides. Their activities were
      determined by the efficiency extrapolation method applied to 4pi (PC)-gamma
      coincidence. Some standardisations, mainly standardisations of EC-beta(+)
      radionuclides, required optimal setting of coincidence parameters, for which new
      procedures based on "the coincidence to total PC count ratios", "a multiple gamma
      window combined from subwindows fractions" and "a source test for PC detection
      efficiency " were introduced. The paper summarises the development of SCC system
      related to findings from detailed analyses of recorded data. These findings are
      not practically achievable by a conventional approach.

PMID- 22401942
TI  - A novel method to determine Poisson's ratio by beta-ray absorption experiment.
AB  - In this paper a new experimental method is applied to determine Poisson's ratio
      of an industrial rubber tape based on the attenuation of beta particles. A simple
      theoretical model is presented and the experimental results are compared with the
      model's prediction. Poisson's ratio of the rubber is obtained by applying a
      steady state strain force. The relatively good agreement between the model's
      prediction and the experimental results could be a verification test for the
      presented method.

PMID- 22401943
TI  - Upregulation of the heteromeric y+LAT2 transporter contributes to ammonia-induced
      increase of arginine uptake in rat cerebral cortical astrocytes.
AB  - Increased l-Arg (Arg) uptake to astrocytes and neurons is thought to contribute
      to enhanced nitric oxide (NO) synthesis and oxidative/nitrosative stress
      associated with hyperammonemia (HA). Recently we had shown that HA increases the
      expression in the brain of y(+)LAT2, an isoform of the y(+)L heteromeric
      transporter which promotes [(3)H]Arg efflux form brain cells in the presence of l
      glutamine (Gln) (Zielinska et al., 2011). In this study, we demonstrate that a
      significant proportion of [(3)H]Arg uptake to cultured cortical astrocytes is
      likewise mediated by system y(+)L, in addition to the uptake showing
      characteristics of systems y(+), B(0+) and b(0+). However, stimulation of
      [(3)H]Arg uptake by treatment with 5mM ammonium chloride ("ammonia") for 48 h
      could be solely ascribed to the y(+)L-mediated component of the uptake. Ammonia
      treatment increased the expression of the brain specific y(+)L isoform, y(+)LAT2,
      both at the mRNA and protein level, and silencing of the Slc7a6 gene coding for
      y(+)LAT2 protein specifically reduced the ammonia-induced [(3)H]Arg uptake. This
      study suggests an important role of y(+)LAT2 in the modulation of NO synthesis in
      the ammonia-exposed astrocytes.

PMID- 22401944
TI  - Putting signalling into context.

PMID- 22401945
TI  - Factors affecting the development of renal failure after abdominal vascular
      surgery.

PMID- 22401946
TI  - [Standardized terminology for disc disease].
AB  - This article reviews the terminology used to describe morphological alterations
      in the intervertebral discs. Radiologists must be able to communicate information
      about the type, location, and severity of these alterations to medical and
      surgical clinicians. It is crucial to use simple, standard, and unified
      terminology to ensure comprehension not only among radiologists but also with
      professionals from the different specialties for whom the radiology reports are
      written (fundamentally traumatologists and neurosurgeons). This terminology will
      help ensure a more accurate diagnosis and better patient management.

PMID- 22401948
TI  - Exocytosis of MTT formazan could exacerbate cell injury.
AB  - MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] method is one
      of the most widely used methods to analyze cell proliferation and viability. It
      is taken up through endocytosis and is reduced by mitochondrial enzymes as well
      as endosomal/lysosomal compartments, then is transported to cell surfaces to form
      needle-like MTT formazans; however the effect of MTT itself still remains
      elusive. Our objective was to investigate the direct effects of MTT on in vitro
      SH-SY5Y cells. Results showed that the endocytosis of MTT did not cause obvious
      lesion and induce cell death, but the metabolism and exocytosis of MTT could
      dramatically damage cells. Our results also indicated that MTT could activate
      apoptosis related factors such as caspase-8, caspase-3 or accelerate the leakage
      of cell contents after the appearance of MTT formazan crystals. The present data
      suggest MTT method should be carefully chosen; otherwise the cell viability would
      be underestimated and incomparable.

PMID- 22401947
TI  - Variants of glutathione s-transferase pi 1 exhibit differential enzymatic
      activity and inhibition by heavy metals.
AB  - Nonsynonymous single nucleotide polymorphisms in glutathione s-transferase pi 1
      (GSTP1; Ile/Val 105, Ala/Val 114) have been associated with altered toxicant
      metabolism in epidemiological cohorts. We explored the impact of GSTP1 genotype
      on enzyme kinetics and heavy metal inhibition in vitro. Four GSTP1 allozymes
      (105/114: Ile/Ala, Val/Ala, Ile/Val, Val/Val) were expressed in and purified from
      Escherichia coli. Enzyme activity assays quantifying the rate of glutathione
      conjugation with 1-chloro-2,4-dinitrobenzene (CDNB) revealed significant
      differences in kinetic parameters depending on genotype (p<0.01). Allozymes with
      Ile105 had better catalytic efficiency and greater affinity for CDNB (mean +/-
      SEM: Ile105 Ala114 K(m)=0.33 +/- 0.07 mM vs. Val105 Ala114 K(m)=1.15 +/- 0.07
      mM). Inhibition of GSTP1 activity by heavy metals was assessed following
      treatment with mercury (inorganic-HgCl(2), methylmercury-MeHg), selenium,
      cadmium, lead, arsenic, and manganese. All allozymes were inhibited by HgCl(2)
      (IC(50) range: 24.1-172 MUM), MeHg (93.9-480 MUM), and selenium (43.7-62.8 MUM).
      Genotype significantly influenced the potency of mercury with GSTP1 Ile105 Val114
      the least sensitive and Val105 Ala114 the most sensitive to inhibition by HgCl(2)
      and MeHg. Overall, genotype of two nonsynonymous polymorphisms in GSTP1
      influenced enzyme kinetics pertaining to an electrophilic substrate and
      inhibition by two mercury species.

PMID- 22401949
TI  - How accurate are clinical decision rules for pediatric minor head injury?

PMID- 22401951
TI  - At risk of undertriage? Testing the performance and accuracy of the emergency
      severity index in older emergency department patients.
AB  - STUDY OBJECTIVE: We test predictive validity, interrater reliability, and
      diagnostic accuracy of the Emergency Severity Index in older emergency department
      (ED) patients and identify reasons for inadequate triage. METHODS: We analyzed
      data of patients aged 65 years or older who were included in a prospective,
      single-center cohort study. Predictive validity was assessed by investigating
      associations of resources, disposition, length of stay, and mortality with
      Emergency Severity Index levels. Diagnostic accuracy was tested by calculating
      sensitivity and specificity of Emergency Severity Index level 1 for the
      prediction of a lifesaving intervention. For the assessment of interrater
      reliability, 2 experts independently reviewed the triage nurses' notes. Agreement
      was estimated as raw agreement and as Cohen's weighted kappa. RESULTS: In total,
      519 older patients were included. Emergency Severity Index level was associated
      with resource consumption (Spearman's rho=-0.449; 95% confidence interval [CI] 
      0.519 to -0.379), disposition (Kendall's tau=-0.452; 95% CI -0.516 to -0.387), ED
      length of stay (Kruskal-Wallis chi(2)=92.5; df=4; P<.001), and mortality (log
      rank chi(2)=37.04; df=3; P<.001). The sensitivity of the Emergency Severity Index
      to predict lifesaving interventions was 0.462 (95% CI 0.232 to 0.709), and the
      specificity was 0.998 (95% CI 0.989 to 1.000). Interrater reliability between
      experts was high (raw agreement 0.917, 95% CI 0.894 to 0.944; Cohen's weighted
      kappa(w)=0.934, 95% CI 0.913 to 0.954). Undertriage occurred in 117 cases. Main
      reasons were neglect of high-risk situations and failure to appropriately
      interpret vital signs. CONCLUSION: In our study, older patients were at risk for
      undertriage. However, our results suggest that the Emergency Severity Index is
      reliable and valid for triage of older patients.

PMID- 22401950
TI  - Observational studies of patients in the emergency department: a comparison of 4
      sampling methods.
AB  - STUDY OBJECTIVE: We evaluate the ability of 4 sampling methods to generate
      representative samples of the emergency department (ED) population. METHODS: We
      analyzed the electronic records of 21,662 consecutive patient visits at an urban,
      academic ED. From this population, we simulated different models of study
      recruitment in the ED by using 2 sample sizes (n=200 and n=400) and 4 sampling
      methods: true random, random 4-hour time blocks by exact sample size, random 4
      hour time blocks by a predetermined number of blocks, and convenience or
      "business hours." For each method and sample size, we obtained 1,000 samples from
      the population. Using chi(2) tests, we measured the number of statistically
      significant differences between the sample and the population for 8 variables
      (age, sex, race/ethnicity, language, triage acuity, arrival mode, disposition,
      and payer source). Then, for each variable, method, and sample size, we compared
      the proportion of the 1,000 samples that differed from the overall ED population
      to the expected proportion (5%). RESULTS: Only the true random samples
      represented the population with respect to sex, race/ethnicity, triage acuity,
      mode of arrival, language, and payer source in at least 95% of the samples.
      Patient samples obtained using random 4-hour time blocks and business hours
      sampling systematically differed from the overall ED patient population for
      several important demographic and clinical variables. However, the magnitude of
      these differences was not large. CONCLUSION: Common sampling strategies selected
      for ED-based studies may affect parameter estimates for several representative
      population variables. However, the potential for bias for these variables appears
      small.

PMID- 22401952
TI  - Ketamine-propofol combination (ketofol) versus propofol alone for emergency
      department procedural sedation and analgesia: a randomized double-blind trial.
AB  - STUDY OBJECTIVE: We determine whether a 1:1 mixture of ketamine and propofol
      (ketofol) for emergency department (ED) procedural sedation results in a 13% or
      more absolute reduction in adverse respiratory events compared with propofol
      alone. METHODS: Participants were randomized to receive either ketofol or
      propofol in a double-blind fashion. Inclusion criteria were aged 14 years or
      older and American Society of Anesthesiology class 1 to 3 status. The primary
      outcome was the number and proportion of patients experiencing an adverse
      respiratory event as defined by the Quebec Criteria. Secondary outcomes were
      sedation consistency, efficacy, and time; induction time; and adverse events.
      RESULTS: A total of 284 patients were enrolled, 142 per group. Forty-three (30%)
      patients experienced an adverse respiratory event in the ketofol group compared
      with 46 (32%) in the propofol group (difference 2%; 95% confidence interval -9%
      to 13%; P=.80). Three ketofol patients and 1 propofol patient received bag-valve
      mask ventilation. Sixty-five (46%) patients receiving ketofol and 93 (65%)
      patients receiving propofol required repeated medication dosing or progressed to
      a Ramsay Sedation Score of 4 or less during their procedure (difference 19%; 95%
      confidence interval 8% to 31%; P=.001). Six patients receiving ketofol were
      treated for recovery agitation. Other secondary outcomes were similar between the
      groups. Patients and staff were highly satisfied with both agents. CONCLUSION:
      Ketofol for ED procedural sedation does not result in a reduced incidence of
      adverse respiratory events compared with propofol alone. Induction time,
      efficacy, and sedation time were similar; however, sedation depth appeared to be
      more consistent with ketofol.

PMID- 22401953
TI  - The growth, photosynthesis and antioxidant defense responses of five vegetable
      crops to phenanthrene stress.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are global environmental problem. To
      better understand the growth and physiological responses to atmospheric PAHs, we
      investigated biomass, photosynthetic machinery and antioxidant system in pakchoi,
      cucumber, flowering chinese cabbage, tomato and lettuce under various levels of
      phenanthrene (PHE) stress. Foliar exposure to PHE for 14d resulted in a dose
      dependent decrease in growth, photosynthesis and chlorophyll contents. With few
      exceptions, antioxidant enzymes (superoxide dismutase, guaicol peroxidase,
      catalase, ascorbate peroxidase and glutathione reductase) were upregulated
      following exposure to PHE. Dose dependent increase in malondialdehyde contents
      together with H(2)O(2) accumulation suggested an occurrence of oxidative stress
      following PHE exposure. However, to some extent, growth and antioxidant defense
      responses differ from species to species. Difference in defense capacity might
      result in different tolerance and phytotoxicity among the studied vegetables.
      Taken together, phytotoxicity of PHE to five vegetables could be sequenced in the
      following order: pakchoi>cucumber>lettuce>tomato>flowering chinese cabbage.

PMID- 22401954
TI  - Toxic effects of PCDD/Fs mixtures on Eisenia andrei earthworms.
AB  - The earthworms Eisenia andrei were used to study the toxicity of PCDD/Fs mixtures
      to earthworms during 28 day of exposure. The experiments were performed on
      artificial soils contaminated with dioxins at levels of C1 (0.1 ng 2, 3, 7, 8
      TCDD/g soil), C2 (1 ng 2, 3, 7, 8-TCDD/g soil) and C3 (1.5 ng 2, 3, 7, 8-TCDD/g
      soil). Effects of PCDD/Fs on survival, growth rate and immune responses;
      phagocytosis and NK-like cell activity, were determined. No mortality was
      observed at the lowest concentration (C1), while mortalities of 10 and 100% were
      noted at the highest concentrations tested C2 and C3, respectively. A significant
      reduction in growth rate was obtained at C2 and no effects at C1. Additionally,
      an inhibition of phagocytic activity and efficiency was observed at higher
      concentrations. In contrast, an enhancement of NK-like cell activity was shown at
      lower concentrations. Based on our results, we hypothesize that the PCDD/Fs
      mixtures tested at levels equal or higher to C2 (1 ng 2378-TCDD/g soil), lead to
      adverse effects on biotic potential and immune functions in E. andrei earthworms.

PMID- 22401955
TI  - Glycan variability on a recombinant IgG antibody transiently produced in HEK-293E
      cells.
AB  - In this study, a recombinant monoclonal IgG antibody was produced by transient
      gene expression (TGE) in suspension-adapted HEK-293E cells. The objective of the
      study was to determine the variation in recombinant IgG yield and glycosylation
      in ten independent transfections. In a ten-day batch process, the variation in
      transient IgG yield in the ten batches was less than 30% with the specific
      productivity averaging 20.2 +/- 2.6 pg/cell/day. We characterized the N
      glycosylation profile of each batch of affinity-purified IgG by intact protein
      and bottom-up mass spectrometry. Four major glycans were identified at Asn(297)
      in the ten batches with the maximum relative deviation for a single glycoform
      being 2.5%. In addition, within any single transfection there was little
      variation in glycoforms over the ten-day culture. Our experimental data indicate
      that with TGE, the production of recombinant IgG with little batch-to-batch
      variation in volumetric yield and protein glycosylation is feasible, even in a
      non-instrumented cultivation system as described here.

PMID- 22401956
TI  - Feeding and reward: ontogenetic changes in an animal model of obesity.
AB  - Given that food is a natural reinforcement, deficits in the reward system can
      lead to disordered eating behavior, inducing or worsening an already existing pre
      obese phenotype. In order to evaluate developmental, food-reward-related measures
      we used the OLETF rat, an animal model of early-onset overeating-induced obesity,
      and a natural CCK-1 receptor knockout. Dopamine-like-receptor type 1 (D1R) and
      D2R levels were examined in a reward-related brain area (Nac shell) and sucrose
      preference was assessed at selected time points from weaning to adulthood
      (postnatal day [PND]90). In addition, a group of OLETF was pair fed (PF) to the
      amount of food consumed by same-age LETO controls (from weaning to PND 90) to
      examine the contribution of overweight to the alteration in DR expression. In
      addition, we examined food "craving"-like behavior by analyzing microstructural
      patterns of licking a palatable liquid diet. OLETF rats expressed significantly
      lower D2R levels than LETO controls only on PND 90. In PF OLETF, weight and D2R
      levels were normalized. In addition, OLETF presented exaggerated preference for
      the high sucrose concentration. After 30-day abstinence, OLETF rats presented
      significant increased initial rate of licking, suggesting food "craving". Thus,
      adult OLETF rats demonstrated altered D2R signaling similar to drug-induced
      sensitization, suggesting a link with their avidity for sucrose and their
      abnormal craving response. However, the current findings of a late deficit
      appearance and the novel PF results suggest that deficits in the
      motivation/regulatory systems of the OLETF rat are a developing process (at least
      from weaning and on) depending on the overeating and obese phenotype of the rats
      and not only on the CCK mutation.

PMID- 22401957
TI  - Regulation of central noradrenergic activity by 5-HT(3) receptors located in the
      locus coeruleus of the rat.
AB  - A functional interaction between serotonergic and noradrenergic systems has been
      shown in the locus coeruleus (LC). Noradrenaline (NA) levels in the prefrontal
      cortex (PFC) are dependent on the firing rate of LC neurons, which is controlled
      by alpha(2) adrenoceptors (alpha2ADR). The aim of the present study was to
      investigate the role of 5-HT(3) receptors (5HT3R) in the modulation of central
      noradrenergic activity. We measured extracellular NA concentrations in the LC and
      PFC by dual-probe microdialysis in awake rats and the firing rate of LC neurons
      by electrophysiological techniques in vitro. Administration of the 5HT3R agonists
      SR57227 (1-100 MUM) and m-chlorophenylbiguanide (mCPBG, 1-100 MUM) into the LC
      increased NA in this nucleus (E(max) = 675 +/- 121% and E(max) = 5575 +/- 1371%,
      respectively) and decreased NA in the PFC (E(max) = -49 +/- 6% and E(max) = -25
      +/- 11%, respectively). Administration of the 5HT3R antagonist Y25130 (50 MUM)
      into LC attenuated SR57227 effect in the LC (E(max) = 323 +/- 28%) and PFC
      (E(max) = -37 +/- 7%). The alpha2ADR antagonist RS79948 (1 MUM) blocked the
      SR57227 effect in the PFC but it did not change the effect in the LC (E(max) =
      677 +/- 202%). In electrophysiological assays, both mCPBG (1-10 MUM) and SR57227
      (1-10 MUM) reduced the firing rate of about 50% of tested LC neurons (maximal
      effect = -37 +/- 2% and -31 +/- 4%, respectively); this effect was partially
      blocked by Y25130 (50 MUM). Administration of RS79948 (1 MUM) reversed the
      inhibition induced by mCPBG. Competition radioligand assays against [(3)H]UK14304
      and [(3)H]RX821002 (alpha2ADR selective drugs) in the rat brain cortex showed a
      very weak affinity of SR57227 for alpha2ADR, whereas the affinity of mCPBG for
      alpha2ADR was 17-fold higher than that of SR57227 for alpha2ADR. The present
      results suggest that 5HT3R stimulate NA release in the LC, which promotes
      simultaneously a decrease in the firing rate of LC neurons through alpha2ADR and
      then a decrease of NA release in terminal areas such as the PFC.

PMID- 22401958
TI  - Differences in amino acid residues in the binding pockets dictate substrate
      specificities of mouse senescence marker protein-30, human paraoxonase1, and
      squid diisopropylfluorophosphatase.
AB  - Senescence marker protein-30 (SMP-30) is a candidate enzyme that can function as
      a catalytic bioscavenger of organophosphorus (OP) nerve agents. We purified SMP
      30 from mouse (Mo) liver and compared its hydrolytic activity towards various
      esters, lactones, and G-type nerve agents with that of human paraoxonase1 (Hu
      PON1) and squid diisopropylfluorophosphatase (DFPase). All three enzymes contain
      one or two metal ions in their active sites and fold into six-bladed beta
      propeller structures. While Hu PON1 hydrolyzed a variety of lactones, the only
      lactone that was a substrate for Mo SMP-30 was d-(+)-gluconic acid delta-lactone.
      Squid DFPase was much more efficient at hydrolyzing DFP and G-type nerve agents
      as compared to Mo SMP-30 or Hu PON1. The K(m) values for DFP were in the
      following order: Mo SMP-30>Hu PON1>squid DFPase, suggesting that the efficiency
      of DFP hydrolysis may be related to its binding in the active sites of these
      enzymes. Thus, homology modeling and docking were used to simulate the binding of
      DFP and selected delta-lactones in the active sites of Hu SMP-30, Hu PON1, and
      squid DFPase. Results from molecular modeling studies suggest that differences in
      metal-ligand coordinations, the hydrophobicity of the binding pockets, and
      limited space in the binding pocket due to the presence of a loop, are
      responsible for substrate specificities of these enzymes.

PMID- 22401959
TI  - Alcohol consumption and premotor corpus callosum in older adults.
AB  - Heavy alcohol consumption is toxic to the brain, especially to the frontal white
      matter (WM), but whether lesser amounts of alcohol negatively impact the brain WM
      is unclear. In this study, we examined the relationship between self-reported
      alcohol consumption and regional WM and grey matter (GM) volume in fifty-six men
      and thirty-seven women (70+- 7years) cognitively intact participants of the
      Baltimore Longitudinal Study of Aging (BLSA) with no history of alcohol abuse. We
      used regional analysis of volumes examined in normalized space (RAVENS) maps
      methodology for WM and GM segmentation and normalization followed by voxel based
      morphometry (VBM) implemented in SPM8 to examine the cross-sectional association
      between alcohol consumption and regional WM (and, separately, GM) volume
      controlling for age, sex, smoking, blood pressure and dietary thiamine intake. WM
      VBM revealed that in men, but not in women, higher alcohol consumption was
      associated with lower volume in premotor frontal corpus callosum. This finding
      suggests that even moderate amounts of alcohol may be detrimental to corpus
      callosum and white matter integrity.

PMID- 22401960
TI  - Quantitative proteomics of transporter expression in brain capillary endothelial
      cells isolated from P-glycoprotein (P-gp), breast cancer resistance protein
      (Bcrp), and P-gp/Bcrp knockout mice.
AB  - The objective of this study was to quantitatively examine the protein expression
      of relevant transporters and other proteins in the brain capillary endothelial
      cells isolated from wild-type mice and P-glycoprotein (P-gp), breast cancer
      resistance protein (Bcrp), and P-gp/Bcrp knockout mice. After the isolation of
      brain capillary endothelial cells, a highly sensitive liquid chromatography
      tandem mass spectrometry method with multiple reaction monitoring was used to
      determine the quantitative expression of membrane transporters at the blood-brain
      barrier (BBB) of the various mouse genotypes. Quantitative expression of 29
      protein molecules, including 12 ATP-binding cassette transporters, 10 solute
      carrier transporters, five receptors, and two housekeeping proteins, was examined
      by quantitative proteomics in the four mouse genotypes. There was no significant
      difference in the expression of P-gp between the wild-type and Bcrp1(-/-) mice.
      Likewise, Bcrp expression was not significantly different between the wild-type
      and Mdr1a/b(-/-) mice. There was no significant difference in the expression of
      any of the measured proteins in the brain capillary endothelial cells across the
      genotypes, except for the lack of expression of the corresponding protein in the
      mice that had a genetic deletion of P-gp or Bcrp. In conclusion, using a
      quantitative proteomic approach, we have shown that there are no changes in the
      expression of several relevant transporters in brain capillary endothelial cells
      isolated from single and combination knockout mice. These data suggest that the
      mechanism behind the functional compensation between P-gp and Bcrp at the BBB is
      not related to compensatory changes in transporter expression.

PMID- 22401961
TI  - Helminths of Cnemidophorus ruthveni (Squamata: Teiidae) from Bonaire, Netherlands
      Antilles, with description of a new species of Alaeuris (Nematoda:
      Pharyngodonidae).
AB  - Alaeuris rinconensis n. sp. (Oxyuroidea, Pharyngodonidae) from the large
      intestine of the Bonaire whiptail lizard, Cnemidophorus ruthveni, is described
      and illustrated. Alaeuris rinconensis n. sp. represents the 13th Neotropical
      species assigned to the genus. It is most similar to Alaeuris iguanae in that
      only these 2 Neotropical species have postbulbar excretory pores; in A. iguanae,
      a tail filament is absent; in A. rinconensis, a tail filament is present. Two
      additional helminth species were found, i.e., the cestode Oochoristica iguanae
      and a nematode, Ozolaimus megatyphlon. Cnemidoporus ruthveni represents a new
      host record for the latter 2 species.

PMID- 22401962
TI  - Identifying multidrug resistant tuberculosis transmission hotspots using
      routinely collected data.
AB  - In most countries with large drug resistant tuberculosis epidemics, only those
      cases that are at highest risk of having MDRTB receive a drug sensitivity test
      (DST) at the time of diagnosis. Because of this prioritized testing,
      identification of MDRTB transmission hotspots in communities where TB cases do
      not receive DST is challenging, as any observed aggregation of MDRTB may reflect
      systematic differences in how testing is distributed in communities. We introduce
      a new disease mapping method, which estimates this missing information through
      probability-weighted locations, to identify geographic areas of increased risk of
      MDRTB transmission. We apply this method to routinely collected data from two
      districts in Lima, Peru over three consecutive years. This method identifies an
      area in the eastern part of Lima where previously untreated cases have increased
      risk of MDRTB. This may indicate an area of increased transmission of drug
      resistant disease, a finding that may otherwise have been missed by routine
      analysis of programmatic data. The risk of MDR among retreatment cases is also
      highest in these probable transmission hotspots, though a high level of MDR among
      retreatment cases is present throughout the study area. Identifying potential
      multidrug resistant tuberculosis (MDRTB) transmission hotspots may allow for
      targeted investigation and deployment of resources.

PMID- 22401963
TI  - [Out-of-hospital cardiac arrest: what differences between France and US?].

PMID- 22401964
TI  - [Acute and post-acute hospitalizations for stroke in France: recent improvements
      (2007-2009)].
AB  - OBJECTIVES: The objectives of this study were to assess the main characteristics
      of acute and post-acute care for transient ischemic attack (TIA) and stroke,
      based on the French national hospitalization databases and their evolutions from
      2007 through 2009. METHODS: Hospitalizations with a main diagnosis of stroke were
      first selected in the 2007, 2008 and 2009 French hospital discharge databases
      (PMSI-MCO). They were then linked in the corresponding national databases of post
      acute hospitalization records (PA), through the common anonymous patient number
      used in every hospitalization database. RESULTS: In France, 138,601 acute
      hospitalizations were registered in 2009, 31,674 TIA and 106,927 strokes, of
      which 91% were in public hospitals. The mean length of stay was 6.4 days for TIA
      and 12.7 days for stroke. Stroke hospitalization in stroke unit increased from
      9.7% in 2007 to 25.9% in 2009 and acute care in hospital having a stroke unit,
      from 22.9% to 47.4%. A third of stroke patients hospitalized in acute care in
      2009 (and not deceased), were linked in the post-acute-care database: 10.4% were
      in rehabilitations facilities (RF) and 23.4%, in post-acute nursing facilities
      (PAN), versus respectively 7.5% and 24% in 2007. DISCUSSION: French national
      hospitalization databases are exhaustive (acute care) or quasi-exhaustive (post
      acute care) and can be linked with a good reliability. However, their validity
      depends on coding accuracy. In this respect, stroke unit hospitalization might be
      underreported. CONCLUSION: The French national hospital databases showed
      consistent improvements in stroke care in recent years. At the acute phase, there
      was an increase in stroke care in both stroke unit and hospital with stroke unit,
      due to the development of stroke care in France. Furthermore, the proportion of
      stroke patient discharged in rehabilitation facilities increased from 7.5% to
      10.4%.

PMID- 22401965
TI  - Activation of the BRCA1/Chk1/p53/p21(Cip1/Waf1) pathway by nitric oxide and cell
      cycle arrest in human neuroblastoma NB69 cells.
AB  - Nitric oxide (NO) works as a bi-modal effector of cell proliferation, inducing
      either the increase or decrease of cell growth when cells are exposed,
      respectively, to low or high NO concentrations. To get further insight into the
      action of NO, we tested the effect of short- and long-lived NO donors on the
      control of the cell cycle in human neuroblastoma NB69 cells. We demonstrated that
      long-time exposure of cells to NO not only decreased the expression and/or the
      phosphorylation of elements involved in the control of the G(1)/S transition,
      such as the transcriptional repressor pRb and cyclin D1, but also down-regulated
      systems controlling the S and G(2)/M phases, such as the phosphorylation of
      Cdk1(cdc2) and the expression of cyclins A and B1. Increasing concentrations of
      NO also induced a biphasic effect on the expression of cyclins D1, A and B1,
      while this effect was less pronounced for cyclin E expression, but the levels of
      mRNAs of those cyclins changed in a distinct and complex manner. NO also changed
      the phosphorylation pattern of cyclin E and decreased the levels of phospho
      cyclins D1 and B1. Moreover, NO decreased the expression of the Cdk inhibitors
      p16(Ink4a) and p19(Ink4d), without affecting p27(Kip1). In contrast, NO induced a
      biphasic effect on p21(Cip1/Waf1) expression. The BRCA1/Chk1/p53 pathway mediated
      the upregulation of p21(Cip1/Waf1). We also demonstrated that the NO-mediated up
      regulation of p21(Cip1/Waf1) was inversely correlated with the activation status
      of the p38MAPK pathway.

PMID- 22401966
TI  - No association between catechol-O-methyltransferase polymorphisms and neurotic
      disorders among mainland Chinese university students.
AB  - This study investigates the genetic association between catechol-O
      methyltransferase (COMT) gene polymorphisms and neurotic disorders. Data were
      derived from a case-control association study of 255 undergraduates affected by
      neurotic disorders and 269 matched healthy undergraduate controls. The
      polymorphisms of eight tag single nucleotide polymorphisms (SNPs) on the COMT
      gene were tested using polymerase chain reaction (PCR)-based Ligase Detection
      Reaction (PCR-LDR). The eight tag SNPs on the COMT gene assessed were not
      associated with neurotic disorders. Our finding suggests that the COMT gene may
      not be a susceptibility gene for neurotic disorders.

PMID- 22401967
TI  - Hypersensitivity to hypercapnia: definition/(s).
AB  - Empirical evidence indicates that panic disorder (PD) patients experience
      hypersensitivity to hypercapnia, a condition in which the blood level of carbon
      dioxide exceeds the normal value. The importance of this research line is
      substantial and indeed, hypercapnic hypersensitivity has been advanced as a
      possible endophenotype of panic. Definitions of "hypersensitivity," however, have
      varied. The purpose of this brief review is to delineate and critique different
      definitions of hypercapnic hypersensitivity. Several definitions - panic attack
      rate, panic symptoms including dyspnea, subjective anxiety, and respiratory
      disturbance - are explored. The review concludes that although no ideal
      definition has emerged, marked anxiety post-hypercapnia has substantial support
      as a putative trait marker of PD. The term "subjective hypersensitivity" (Coryell
      et al., 2001) is re-introduced to denote pronounced anxiety post-hypercapnia and
      recommended for use along with its previous definition: increased self-reported
      anxiety measured on a continuous visual analog scale, already widely in use. Due
      to the well-established link between panic and respiration, definitional
      candidates focusing on aberrant respiratory response - less investigated as trait
      markers of PD in high risk studies - warrant scrutiny as well. Several reasons
      why definitional clarity might be beneficial are presented, along with ideas for
      future research.

PMID- 22401968
TI  - Refining clinical phenotypes by contrasting ethnically different populations with
      schizophrenia from Australia, India and Sarawak.
AB  - We contrasted demographic and clinical characteristics in transethnic
      schizophrenia populations from Australia (n=821), India (n=520) and Sarawak,
      Malaysia (n=298) and proposed cultural explanations for identified site
      differences. From these we aimed to identify candidate variables free from
      significant cultural confounding that are hence suitable for inclusion in genetic
      analyses. We observed five phenomena: (1) more individuals were living alone in
      Australia than India or Sarawak; (2) drug use was lower in India than Australia
      or Sarawak; (3) duration of untreated psychosis (DUP) was longer in India than
      Australia or Sarawak; (4) the rate of schizoaffective disorder was lower in India
      than Australia or Sarawak; and (5) age at psychosis onset (AAO) was older in
      Sarawak than Australia or India. We suggest that site differences for living
      arrangements, drug use and DUP are culturally confounded. The schizoaffective
      site difference likely results from measurement bias. The AAO site difference,
      however, has no obvious cultural or measurement bias explanation. Therefore, this
      may be an ideal candidate for use in genetic studies, given that genetic variants
      affecting AAO have already been proposed.

PMID- 22401969
TI  - Emotion regulation deficits in eating disorders: a marker of eating pathology or
      general psychopathology?
AB  - Preliminary evidence indicates that individuals with eating disorders (ED) show
      emotion regulation (ER) difficulties. However, it is yet unclear whether
      different types of ED differ in their ER profile and whether certain ER
      difficulties are specific for ED or rather a transdiagnostic factor. Twenty women
      with anorexia nervosa (AN), 18 with bulimia nervosa (BN), 25 with binge eating
      disorder (BED), 15 with borderline personality disorder (BPD), 16 with major
      depressive disorder (MDD) and 42 female healthy controls (HC) were administered
      the Emotion Regulation Questionnaire, the Inventory of Cognitive Affect
      Regulation Strategies, the Difficulties in Emotion Regulation Scale and the
      Affect Intensity Measure. The ED groups reported significantly higher levels of
      emotion intensity, lower acceptance of emotions, less emotional awareness and
      clarity, more self-reported ER problems as well as decreased use of functional
      and increased use of dysfunctional emotion regulation strategies when compared to
      HC. No significant differences between the ED groups emerged for most ER
      variables. However, there were indications that the BED group may show a slightly
      more adaptive pattern of ER than the two other ED groups. As a whole, all
      clinical groups performed very similar on most ER variables and reported more
      difficulties regulating their emotions than HC. The findings suggest that ER
      difficulties are not linked to a particular diagnostic category. Instead, ER
      difficulties appear to be a transdiagnostic risk and/or maintenance factor rather
      than being disorder-specific.

PMID- 22401970
TI  - Alexithymia in Chinese chronic obstructive pulmonary disease (COPD) patients: the
      prevalence and related factors of alexithymia.
AB  - In this study, 53 Chinese COPD moderate outpatients and 50 health controls,
      matched for age, family income and education level, were recruited to assess the
      prevalence of Alexithymia and its relationship to socio-demographic factors and
      pulmonary function. Alexithymia was measured with 20-item Toronto Alexithymia
      Scale (TAS-20). The patients' socio-demographic variables and the forced
      expiratory volume in one second percentage of predicted (FEV(1)% predicted) were
      recorded. The results indicated that alexithymia was significantly more common in
      the Chinese COPD patients than in controls. Male patients presented higher TAS-20
      total scores and externally oriented thinking (EOT) scores than the females.
      Elder age and higher family income were connected with the patients' lower TAS-20
      indexes (except for difficulty identify feeling [DIF]). All the TAS-20 indexes
      were negatively associated with FEV(1)% predicted. These findings suggested that,
      in the management of COPD, alexithymia feature should not be ignored and the
      appropriate psychotherapeutic treatment for Alexithymia should be applied.

PMID- 22401971
TI  - Beliefs about causes, behavioural manifestations and treatment of borderline
      personality disorder in a community sample.
AB  - This study was part of a programmatic series into mental health literacy,
      specifically lay people's knowledge of causes, manifestations and cures of
      borderline personality disorder (BPD). The aim was to determine to what extent
      non-experts understood BDP and to what extent they held erroneous beliefs about
      specific aspects of the causes and cures for the disorder. A convenience sample
      of 102 participants completed a vignette-identification task that required them
      to answer open-ended questions about hypothetical people with four psychological
      problems, one of which was BPD and a 50-item questionnaire divided into three
      sections about BDP. Analysis of the vignette-identification task revealed very
      low rates of recognition for BPD, with participants significantly more likely to
      identify depression, schizophrenia or psychopathy. Participants generally
      favoured psychological and sociological treatments, as well as rating early
      trauma and stress as possible causes of the symptoms of the person described in
      the BDP vignette. There were logical relationships between perceptions of cause
      and cure. The results suggest that participants hold certain coherent beliefs
      (psychological, sociological, biological or theological) regarding aetiology and
      treatments of BPD. Further, the findings suggest the need for greater awareness
      and educational programmes to inform the general public accurately regarding BPD
      and to improve mental health literacy.

PMID- 22401972
TI  - Stigma as a predictor of insight in schizophrenia.
AB  - Insight in schizophrenia can be seen as a multifactorial phenomenon. Although
      multifactorial pathways have also been suggested for insight formation,
      motivational explanations have rarely been tested. The present study explores
      stigma as one possible determinant of a motivated lack of insight in integrated
      models of insight formation. It examines the contribution of socio-demographic
      and clinical variables, neurocognitive functions, symptoms, and stigma to the
      prediction of insight into illness. Patients diagnosed with schizophrenia
      spectrum disorders (N=111) participated in a comprehensive battery of instruments
      to measure insight dimensions, stigma, neurocognitive functions, symptoms, socio
      demographic and clinical variables. Blockwise multiple regression analysis
      indicates significant association of variability in insight dimensions with
      gender (7%) and stigma (i. e., stereotype agreement: 5%). Our findings
      demonstrate an incremental validity of stigma, which indicates a motivational
      pathway of insight formation. This study enables better understanding of the
      multifactorial nature of insight, which should be considered in therapeutic
      interventions to improve insight. The roles of gender and neurocognitive
      functions in insight formation are also discussed.

PMID- 22401973
TI  - Recreational gamblers with and without parental addiction.
AB  - Research has found that children who have parents with an addiction may be more
      vulnerable to developing psychopathology compared to children without parental
      addiction. We compared young adult, recreational gamblers with and without
      parental addiction on measures of gambling behavior and impulsivity. A total of
      286 recreational gamblers (defined as having gambled at least five times in the
      past 12 months) between the ages of 18 and 29 participated in an initial intake
      of a longitudinal study assessing susceptibility to pathological gambling.
      Trained staff members interviewed subjects, and subjects completed cognitive
      testing and self-report measures. Fifty-three subjects (18.53%) reported at least
      one parent with an addiction (including alcohol and substance dependence and
      pathological gambling). Subjects with at least one addicted parent were
      significantly more likely to report problems resulting from gambling, have
      significantly greater rates of psychiatric comorbidity, and report significantly
      more current marijuana and tobacco use. Subjects with an addicted parent were not
      significantly different on measures of impulsivity. These findings suggest that
      even at a stage of low-risk gambling, before what has been considered a
      psychopathology arises, those with a possible environmental and/or genetic risk
      of addiction exhibit a range of problematic behaviors.

PMID- 22401974
TI  - Test-retest reliability of the proposed DSM-5 eating disorder diagnostic
      criteria.
AB  - The proposed DSM-5 classification scheme for eating disorders includes both major
      and minor changes to the existing DSM-IV diagnostic criteria. It is not known
      what effect these modifications will have on the ability to make reliable
      diagnoses. Two studies were conducted to evaluate the short-term test-retest
      reliability of the proposed DSM-5 eating disorder diagnoses: anorexia nervosa,
      bulimia nervosa, binge eating disorder, and feeding and eating conditions not
      elsewhere classified. Participants completed two independent telephone interviews
      with research assessors (n=70 Study 1; n=55 Study 2). Fair to substantial
      agreements (kappa=0.80 and 0.54) were observed across eating disorder diagnoses
      in Study 1 and Study 2, respectively. Acceptable rates of agreement were
      identified for the individual eating disorder diagnoses, including DSM-5 anorexia
      nervosa (kappa's of 0.81 to 0.97), bulimia nervosa (kappa=0.84), binge eating
      disorder (kappa's of 0.75 and 0.61), and feeding and eating disorders not
      elsewhere classified (kappa's of 0.70 and 0.46). Further, improved short-term
      test-retest reliability was noted when using the DSM-5, in comparison to DSM-IV,
      criteria for binge eating disorder. Thus, these studies found that trained
      interviewers can reliably diagnose eating disorders using the proposed DSM-5
      criteria; however, additional data from general practice settings and community
      samples are needed.

PMID- 22401975
TI  - Is non-suicidal self-injury an "addiction"? A comparison of craving in substance
      use and non-suicidal self-injury.
AB  - There is debate among researchers regarding the most appropriate conceptual model
      of non-suicidal self-injury (NSSI). Some argue that NSSI is best viewed within an
      addictions framework. Because craving of substances is a key concept in the
      addictions literature, we sought to compare the nature of craving in NSSI and
      substance use. Measures of NSSI, substance use, and craving were administered to
      a sample of adolescents (n=58) receiving psychiatric treatment. It was found that
      total craving scores were significantly lower for NSSI than for substances. Item
      level analyses suggested that substances are craved in a variety of contexts,
      whereas NSSI is typically craved in the context of negative emotions. The pattern
      of results remained the same when analyses were limited to patients who engaged
      in both NSSI and substance use. Thus, findings appear to be due to differences in
      the nature of the behaviors themselves rather than to individual differences
      between those who engage in NSSI or use substances. We conclude that, while both
      behaviors have powerful reinforcement contingencies, NSSI appears to be almost
      exclusively maintained by negative reinforcement (e.g., the reduction of aversive
      emotions). Findings are more consistent with emotion regulation than addiction
      models of NSSI.

PMID- 22401976
TI  - Interpersonal and intrapersonal links to body appreciation in college women: an
      exploratory model.
AB  - Based on theory and findings from qualitative and quantitative research, we
      developed and investigated a model of positive body image. This model placed body
      appreciation in a mediating role, linking interpersonal (caregiver eating
      messages, adult attachment) and intrapersonal (perfectionism) variables to
      intuitive eating and depressive symptoms. Path analysis supported our model for
      249 college women. Restrictive/critical caregiver eating messages, attachment
      anxiety, and discrepancy (maladaptive) perfectionism inversely predicted body
      appreciation, while order (adaptive) perfectionism positively predicted body
      appreciation. In turn, body appreciation positively predicted intuitive eating
      but not depressive symptoms. Body appreciation was upheld as a mediator:
      discrepancy perfectionism, attachment anxiety, and restrictive/critical caregiver
      eating messages inversely predicted intuitive eating largely through their
      negative connection with body appreciation. These findings underscore the
      importance of women's internalized messages about eating, weight, and
      relationships to their capacity to appreciate their body and respect it by eating
      according to its internal hunger/satiety cues.

PMID- 22401977
TI  - Influence of bitches sex pheromones on the heart rate and other chosen parameters
      of blood flow in stud dogs (Canis familiaris).
AB  - The aim of this study was to verify the usefulness of the measurement of chosen
      cardiovascular activity parameters for examination of sex pheromones effects in
      male dogs. We evaluated the influence of the bitches' sexual pheromones (BSP) on
      heart rate (HR) with the use of a Holter monitor, and chosen parameters of blood
      flow in vessels of penis, testes and kidney, with color-coded and pulsed Doppler
      ultrasonography. We found that the BSP increased HR in all examined males even
      without showing any other signs of arousal. There were no changes in the RI
      (resistant index) and PI (pulsative index) in any trials during the pheromone
      presentation. The increase in blood flow intensity was noted in penile vessels
      but not in the testes and kidney. We concluded that measurement of flow intensity
      in the penis as well as the changes in heart rate as the male's reaction to the
      BSP can be useful in research concerning sex pheromones in dogs.

PMID- 22401978
TI  - Molecular and pathological investigations of EHV-1 and EHV-4 infections in horses
      in Turkey.
AB  - The aim of the present study was to investigate abortion storms that occurred in
      the Marmara region of Turkey in 2008-2009 using a real-time PCR. Two aborted
      foetuses were necropsied and histo-pathological findings reported herein. Ten
      lungs, 3 brains and one nasal swab from 10 aborted foetuses, 6 nasal swabs and 3
      vaginal swabs from aborting mares were included in this study. EHV-1 was isolated
      from the lung, liver and brain of 1 aborted foetus. EHV-1 DNA was detected in the
      lungs, livers and spleens of 2 necropsied foetuses and in 3 lungs from 10
      foetuses submitted for diagnosis. A brain from one of the aborted foetuses was
      also positive for EHV-1 DNA. EHV-4 DNA was detected only in a nasal swab of one
      of the tested foetuses. Neither EHV-1 nor EHV-4 DNA was detected in the swabs of
      aborting mares. Sequence analysis of the glycoprotein B of the strains was
      performed and a phylogenetic tree was generated. The results indicated that 4 of
      the 5 Turkish EHV-1 strains (TR02, TR03, TR04 and TR05) clustered together; the
      fifth strain (TR01) was slightly removed from the group and clustered with other
      EHV-1 from various origins. Single nucleotide polyporphism (SNP in ORF30)
      associated with neuropathogenesis was not detected in any of the strains. At
      necropsy, sub-milier focal necrosis in the liver and spleen was observed.
      Microscopically, focal coagulation necrosis and marked eosinophilic intranuclear
      and intracytoplasmic inclusion bodies in the hepatocytes localised around the
      necrotic areas in the liver. Severe coagulation necrosis in white pulp of the
      spleen was also observed.

PMID- 22401979
TI  - Allelic transcripts dosage effect in morphologically normal ovarian cells from
      heterozygous carriers of a BRCA1/2 French Canadian founder mutation.
AB  - We hypothesized that the transcriptome of primary cultures of morphologically
      normal ovarian surface epithelial cells could be altered by the presence of a
      heterozygous BRCA1 or BRCA2 mutation. We aimed to discover early events
      associated with ovarian carcinogenesis, which could represent putative targets
      for preventive strategies of this silent killer tumor. We identified the first
      molecular signature associated with French Canadian BRCA1 or BRCA2 founder
      mutations in morphologically normal ovarian epithelial cells. We discovered that
      wild-type and mutated BRCA2 allelic transcripts were expressed not only in
      morphologically normal but also in tumor cells from BRCA2-8765delAG carriers.
      Further analysis of morphologically normal ovarian and tumor cells from BRCA1
      4446C>T carriers lead to the same observation. Our data support the idea that one
      single hit in BRCA1 or BRCA2 is sufficient to alter the transcriptome of
      phenotypically normal ovarian epithelial cells. The highest level of BRCA2
      mutated allele transcript expression was measured in cells originating from the
      most aggressive ovarian tumor. The penetrance of the mutation and the
      aggressiveness of the related tumor could depend on a dosage effect of the
      mutated allele transcript.

PMID- 22401980
TI  - Aerosolized 3-bromopyruvate inhibits lung tumorigenesis without causing liver
      toxicity.
AB  - 3-Bromopyruvate, an alkylating agent and a well-known inhibitor of energy
      metabolism, has been proposed as a specific anticancer agent. However, the
      chemopreventive effect of 3-bromopyruvate in lung tumorigenesis has not been
      tested. In this study, we investigated the chemopreventive activity of 3
      bromopyruvate in a mouse lung tumor model. Benzo(a)pyrene was used to induce lung
      tumors, and 3-bromopyruvate was administered by oral gavage to female A/J mice.
      We found that 3-bromopyruvate significantly decreased tumor multiplicity and
      tumor load by 58% and 83%, respectively, at a dose of 20 mg/kg body weight by
      gavage. Due to the known liver toxicity of 3-bromopyruvate in animal models given
      large doses of 3-bromopyruvate, confirmed in this study, we decided to test the
      chemopreventive activity of aerosolized 3-bromopyruvate in the same lung tumor
      model. As expected, aerosolized 3-bromopyruvate similarly significantly decreased
      tumor multiplicity and tumor load by 49% and 80%, respectively, at a dose of 10
      mg/mL by inhalation. Interestingly, the efficacy of aerosolized 3-bromopyruvate
      did not accompany any liver toxicity indicating that it is a safer route of
      administering this compound. Treatment with 3-bromopyruvate increased
      immunohistochemical staining for cleaved caspase-3, suggesting that the lung
      tumor inhibitory effects of 3-bromopyruvate were through induction of apoptosis.
      3-Bromopyruvate also dissociated hexokinase II from mitochondria, reduced
      hexokinase activity, and blocked energy metabolism in cancer cells, finally
      triggered cancer cell death and induced apoptosis through caspase-3, and PARP in
      human lung cancer cell line. The ability of 3-bromopyruvate to inhibit mouse lung
      tumorigenesis, in part through induction of apoptosis, merits further
      investigation of this compound as a chemopreventive agent for human lung cancer.

PMID- 22401981
TI  - Clinical profiles predict early nonadherence to adjuvant endocrine treatment in a
      prospective breast cancer cohort.
AB  - Nonadherence to adjuvant endocrine breast cancer treatment adversely affects
      disease-free and overall survival. Clinical predictors of nonadherence may allow
      for specific interventions to reduce nonadherence and improve survival. The aim
      was to investigate whether clinical characteristics predict nonadherence.
      Clinical characteristics and information on adherence were obtained from 417
      patients with breast cancer in a population-based prospective cohort from
      southern Sweden using patient charts, pathology reports, and questionnaires
      filled out at the 1- and 2-year follow-up visits. At the 1- and 2-year follow-up
      visits, 36 (8.6%) and 33 (9.7%) patients were nonadherent, respectively. Thirteen
      of the nonadherent patients declined treatment and were never prescribed
      endocrine treatment. A body mass index (BMI) < 25 kg/m(2), preoperative current
      smoking, and drinking alcohol less often than twice a month predicted
      nonadherence at the 1-year [relative risk (RR), 5.24; 95% confidence interval
      (CI), 2.75-9.97] and the 2-year visits (RR, 4.07; 95% CI, 2.11-7.84) in patients
      with at least two of these clinical characteristics. When low histologic grade
      (I) was added to the model, having at least two of these four clinical
      characteristics predicted nonadherence at the 1-year (RR, 4.94; 95% CI, 2.46
      10.00) and the 2-year visits (RR, 4.74; 95% CI, 2.28-9.87), the two profiles had
      a sensitivity ranging from 60.6% to 72.7%, whereas the specificity ranged from
      68.0% to 78.4%. Nonadherence at the 1-year visit was associated with an increased
      risk for early breast cancer events (HR, 2.97; 95% CI, 1.08-8.15), adjusted for
      age and tumor characteristics. In conclusion, two clinical profiles predicted
      early nonadherence and may allow for targeted interventions to increase adherence
      if validated in an independent cohort.

PMID- 22401982
TI  - The synthetic triterpenoid CDDO-methyl ester delays estrogen receptor-negative
      mammary carcinogenesis in polyoma middle T mice.
AB  - Novel drugs are needed for the prevention and treatment of breast cancer.
      Synthetic triterpenoids are a promising new class of compounds with activity in a
      variety of preclinical cancer models. We tested activity of the methyl ester
      derivative of the synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien
      28-oic acid (CDDO-Me), in a relevant model of estrogen receptor-negative breast
      cancer, the polyoma-middle T (PyMT), in which the oncoprotein drives
      carcinogenesis. The developing tumors recapitulate key features of the human
      disease. Mice were fed CDDO-Me (50 mg/kg diet), starting at 4 weeks of age. CDDO
      Me significantly increased the age of mice at onset of first tumor (P < 0.001) by
      an average of 4.3 weeks and overall survival (P < 0.001) by 5.2 weeks. The drug
      also inhibited the infiltration of tumor-associated macrophages into mammary
      glands of PyMT mice at 12 weeks of age and reduced levels of the chemokines
      CXCL12 and CCL2 in primary PyMT mammary tumor cells. Treatment with this
      multifunctional drug also inhibited secretion of matrix metalloproteinase-9 in
      primary tumor cells from PyMT mice and decreased proliferation of these cells by
      inhibiting cyclin D1 and decreasing phosphorylation of epidermal growth factor
      receptor and STAT3.

PMID- 22401983
TI  - The occupational impact of sleep quality and insomnia symptoms.
AB  - While the importance of assessing the occupational consequences of insomnia is
      emphasized in clinical nosologies and research guidelines, there is little
      consensus on which aspects of occupational performance should be assessed, the
      most methodologically justifiable measures of insomnia and work performance, and
      how outcomes should be reported. The present review was designed to summarize and
      methodologically critique the assessment of those aspects of occupational
      performance most impacted by (or most frequently associated with) insomnia
      symptoms. The 30 studies which met the review inclusion criteria broadly
      addressed six domains of occupational functioning: absenteeism; workplace
      accidents; productivity; punctuality; job satisfaction and career progression.
      Collectively, study outcomes support the conclusions that insomnia symptoms: are
      consistently associated with excess absenteeism; elevate accident risk in the
      workplace; reduce subjectively experienced workplace productivity (at least in
      the shorter term); inhibit career progression; and can degrade job satisfaction.
      Study outcomes do not support the conclusion that people with insomnia are
      significantly less punctual than other workers. The overall value of the
      occupational sleep-health literature, however, is limited by a lack of
      comparability among studies. In particular, there is a clear need to standardize
      definitions of sleep and occupational outcomes, and to recognize the confounding
      influence of health variables on occupational performance and sleep.

PMID- 22401984
TI  - Impact of soft and hard insole density on postural stability in older adults.
AB  - A significant predictor of falls in the elderly population is attributed to
      postural instability. Thus, it is important to identify and implement practical
      clinical interventions to enhance postural stability in older adults. Shoe
      insoles have been identified as a mechanism to enhance postural control, and our
      study aimed to evaluate the impact of 2 shoe insoles on static standing balance
      in healthy, older adults compared with standing posture while barefoot. We
      hypothesized that both hard and soft shoe insoles would decrease postural sway
      compared with the barefoot condition. Indeed, excursion distances and sway areas
      were reduced, and sway velocity was decreased when wearing insoles. The hard
      insole was also effective when visual feedback was removed, suggesting that the
      more rigid an insole, the greater potential reduction in fall risk. Thus, shoe
      insoles may be a cost-effective, clinical intervention that is easy to implement
      to reduce the risk of falling in the elderly population.

PMID- 22401985
TI  - Functional decline in hospitalized older adults: can nursing make a difference?
AB  - Function-focused care (FFC) is an approach to care in which nurses help patients
      engage in activities of daily living (ADL) and physical activity, with the goal
      of preventing avoidable functional decline. This prospective, observational
      study, conducted with hospitalized older adults (N = 93) examined: 1) the
      demographic and clinical characteristics of patients who were provided FFC
      activity, and 2) the relationship between change in physical activity and FFC
      activities. Patients who received FFC were more likely: to be younger (P = .028);
      had one or more falls during the hospitalization (P = .048); had demonstrated
      better functional performance at admission (P = .004) and better physical
      capability, measured by the Tinetti gait and balance scale (P = .004). FFC was
      associated with less decrement in ADL function, admission to discharge, while
      considering patient characteristics (t = 7.6; P < .008). Results suggest that
      hospitalized older persons can benefit from FFC.

PMID- 22401987
TI  - Distinct patterns of brain function in children with isolated spelling
      impairment: new insights.
AB  - Studies investigating reading and spelling difficulties heavily focused on the
      neural correlates of reading impairments, whereas spelling impairments have been
      largely neglected so far. Hence, the aim of the present study was to investigate
      brain structure and function of children with isolated spelling difficulties.
      Therefore, 31 children, aged ten to 15 years, were investigated by means of
      functional MRI and DTI. This study revealed that children with isolated spelling
      impairment exhibit a stronger right hemispheric activation compared to children
      with reading and spelling difficulties and controls, when engaged in an
      orthographic decision task, presumably reflecting a highly efficient serial
      grapheme-phoneme decoding compensation strategy. In addition, children with
      spelling impairment activated bilateral inferior and middle frontal gyri during
      processing correctly spelled words and misspelled words, whereas the other two
      groups showed bilateral activation only in the misspelled condition, suggesting
      that additional right frontal engagement could be related to generally higher
      task demand and effort. DTI analyses revealed stronger frontal white matter
      integrity (fractional anisotropy) in controls (compared to spelling and reading
      impaired children), whereas no structural differences between controls and
      spelling impaired children were observed.

PMID- 22401988
TI  - Preserved visual language identification despite severe alexia.
AB  - Patients with letter-by-letter alexia may have residual access to lexical or
      semantic representations of words despite severely impaired overt word
      recognition (reading). Here, we report a multilingual patient with severe letter
      by-letter alexia who rapidly identified the language of written words and
      sentences in French and English while he had great difficulty in reading them,
      judging their lexical status or extracting semantic information. Lexical decision
      was strongly influenced by the orthographic structure of stimuli: whereas he
      easily determined the lexical status of illegal nonwords (e.g., 'rsdo'), he had
      random performance with legal pseudowords (e.g., 'binus'). When asked to
      determine the language of meaningless letter trigrams with high frequency in the
      English or French orthography (e.g., 'oth' or 'iqu') his performance was
      significantly above chance. In contrast, similarly to healthy participants his
      language decision was at chance with low-frequency trigrams. These findings
      suggest that written language identification relies on sublexical processing of
      orthographic rules specific to each language.

PMID- 22401986
TI  - Differences in resting-state functional magnetic resonance imaging functional
      network connectivity between schizophrenia and psychotic bipolar probands and
      their unaffected first-degree relatives.
AB  - BACKGROUND: Schizophrenia and bipolar disorder share overlapping symptoms and
      genetic etiology. Functional brain dysconnectivity is seen in both disorders.
      METHODS: We compared 70 schizophrenia and 64 psychotic bipolar probands, their
      respective unaffected first-degree relatives (n = 70, and n = 52), and 118
      healthy subjects, all group age-, gender-, and ethnicity-matched. We used
      functional network connectivity analysis to measure differential connectivity
      among 16 functional magnetic resonance imaging resting state networks. First, we
      examined connectivity differences between probands and control subjects. Next, we
      probed these dysfunctional connections in relatives for potential endophenotypes.
      Network connectivity was then correlated with Positive and Negative Syndrome
      Scale (PANSS) scores to reveal clinical relationships. RESULTS: Three different
      network pairs were differentially connected in probands (false-discovery rate
      corrected q < .05) involving five individual resting-state networks: (A)
      fronto/occipital, (B) anterior default mode/prefrontal, (C) meso/paralimbic, (D)
      fronto-temporal/paralimbic, and (E) sensory-motor. One abnormal pair was unique
      to schizophrenia, (C-E), one unique to bipolar, (C-D), and one (A-B) was shared.
      Two of these three combinations (A-B, C-E) were also abnormal in bipolar
      relatives but none was normal in schizophrenia relatives (nonsignificant trend
      for C-E). The paralimbic circuit (C-D), which uniquely distinguished bipolar
      probands, contained multiple mood-relevant regions. Network relationship C-D
      correlated significantly with PANSS negative scores in bipolar probands, and A-B
      with PANSS positive and general scores in schizophrenia. CONCLUSIONS:
      Schizophrenia and psychotic bipolar probands share several abnormal resting state
      network connections, but there are also unique neural network underpinnings
      between disorders. We identified specific connections that might also be
      candidate psychosis endophenotypes.

PMID- 22401989
TI  - Structural correlates for lexical efficiency and number of languages in non
      native speakers of English.
AB  - We used structural magnetic resonance imaging (MRI) and voxel based morphometry
      (VBM) to investigate whether the efficiency of word processing in the non-native
      language (lexical efficiency) and the number of non-native languages spoken (2+
      versus 1) were related to local differences in the brain structure of bilingual
      and multilingual speakers. We dissociate two different correlates for non-native
      language processing. Firstly, multilinguals who spoke 2 or more non-native
      languages had higher grey matter density in the right posterior supramarginal
      gyrus compared to bilinguals who only spoke one non-native language. This is
      interpreted in relation to previous studies that have shown that grey matter
      density in this region is related to the number of words learnt in bilinguals
      relative to monolinguals and in monolingual adolescents with high versus low
      vocabulary. Our second result was that, in bilinguals, grey matter density in the
      left pars opercularis was positively related to lexical efficiency in second
      language use, as measured by the speed and accuracy of lexical decisions and the
      number of words produced in a timed verbal fluency task. Grey matter in the same
      region was also negatively related to the age at which the second language was
      acquired. This is interpreted in terms of previous findings that associated the
      left pars opercularis with phonetic expertise in the native language.

PMID- 22401990
TI  - Electrophysiological evidence for phonological priming in Spanish Sign Language
      lexical access.
AB  - Interactive activation models of lexical access assume that the presentation of a
      given word activates not only its lexical representation but also those
      corresponding to words similar in form. Current theories are based on data from
      oral and written languages, and therefore signed languages represent a special
      challenge for existing theories of word recognition and lexical access since they
      allow us to question what the genuine fundamentals of human language are and what
      might be modality-specific adaptation. The aim of the present study is to
      determine the electrophysiological correlates and time course of phonological
      processing of Spanish Sign Language (LSE). Ten deaf native LSE signers and ten
      deaf non-native but highly proficient LSE signers participated in the experiment.
      We used the ERP methodology and form-based priming in the context of a delayed
      lexical decision task, manipulating phonological overlap (i.e. related prime
      target pairs shared either handshape or location parameters). Results showed that
      both parameters under study modulated brain responses to the stimuli in different
      time windows. Phonological priming of location resulted in a higher amplitude of
      the N400 component (300-500 ms window) for signs but not for non-signs. This
      effect may be explained in terms of initial competition among candidates.
      Moreover, the fact that a higher amplitude N400 for related pairs was found for
      signs but not for non-signs points to an effect at the lexical level. Handshape
      overlap produced a later effect (600-800 ms window). In this window, a more
      negative-going wave for the related condition than for the unrelated condition
      was found for non-signs in the native signers group. The findings are discussed
      in relation to current models of lexical access and word recognition. Finally,
      differences between native and non-native signers point to a less efficient use
      of phonological information among the non-native signers.

PMID- 22401991
TI  - Comparative analysis of multiparametric magnetic resonance and PET-CT in the
      management of local recurrence after radical prostatectomy for prostate cancer.
AB  - PURPOSE: Our aim was to assess whether multiparametric magnetic resonance and PET
      CT can have a role in detecting local recurrence in patients with biochemical
      recurrence after radical prostatectomy. METHODS: We reviewed the recent
      international literature by carrying out a PUBMED search. RESULTS: We critically
      reviewed 11 recent original studies about the use of PET-CT and 5 recent studies
      about the use of multiparametric magnetic resonance. PET-CT has not shown
      significant results in terms of detection rate for local recurrence in patients
      with low level of PSA. Multiparametric magnetic resonance showed encouraging
      results to detect local recurrence in patients with low PSA and with small
      diameter lesions. CONCLUSIONS: Currently, most important urological societies do
      not consider multiparametric magnetic resonance and PET-CT in the follow-up of
      patients with suspected local recurrence after radical prostatectomy. We can
      assert that multiparametric magnetic resonance seems to have excellent results in
      detecting local recurrence in patients submitted to radical prostatectomy and
      PSA<1.5 ng/ml.

PMID- 22401992
TI  - MyD88 deficiency results in both cognitive and motor impairments in mice.
AB  - The myeloid differentiation primary response gene 88 (MyD88) product is the most
      common adaptor protein implicated in Toll-like and interleukin receptor (TIR)
      domain signaling and thus plays an important role in the innate immune system.
      Despite the fact that the MyD88-dependent pathway has emerged as an important
      player in cell death processes described in several animal models of
      neurodegenerative disorders, the contribution of this pathway to specific
      behavioral phenotypes has been largely ignored. To understand the full
      implication of this pathway, we tested MyD88(-/-) mice for both motor and
      cognitive functions in normal conditions. MyD88(-/-) mice displayed impaired
      spatial and working memory as detected by the Barnes maze, the water T-maze and
      the passive avoidance tests. Furthermore, MyD88(-/-) mice demonstrated
      hypolocomotion in the open-field and wheel activity systems, as well as
      impairments in motor coordination and balance using the pole test and the
      rotarod. Our findings shed light on behavioral alterations that are associated
      with the deletion of the MyD88 protein in physiological conditions. These
      behavioral effects should be taken into consideration when assessing the role of
      the MyD88-dependent pathway in various infectious and non-infectious conditions.

PMID- 22401993
TI  - Increased corticosteroid sensitivity by a long acting beta2 agonist formoterol
      via beta2 adrenoceptor independent protein phosphatase 2A activation.
AB  - Long-acting beta2-adrenoceptor agonists (LABAs) are reported to enhance anti
      inflammatory effects of corticosteroids in vitro and in vivo, although the
      molecular mechanisms have not yet been elucidated. We investigated the role of
      serine/threonine protein phosphatase 2A (PP2A) on regulation of corticosteroid
      sensitivity via inhibition of glucocorticoid receptor (GR) phosphorylation as the
      target of formoterol, an LABA. Corticosteroid sensitivity was determined as IC50
      to dexamethasone (Dex) on TNFalpha-induced IL-8 release in a U937 monocytic cell
      line (Dex-IC50). Phosphorylation levels of GR-Ser226 and c-Jun N-terminal kinase
      (JNK) were determined by western-blotting. Phosphatase activity of immunopurified
      PP2A was measured by fluorescence-based assay. Exposure to IL-2/IL-4 for 48 h
      decreased Dex sensitivity with a concomitant increase of GR phosphorylation at
      Ser226 with JNK1 activation. Formoterol restored Dex sensitivity by inhibiting
      phosphorylation of GR-Ser226 and JNK1. PP2A inhibition by okadaic acid, a
      phosphatase inhibitor, abrogated formoterol-mediated effects. In addition,
      formoterol enhanced PP2A activity in intact or IL-2/IL-4 treated U937 cells and
      human peripheral blood mononuclear cells. In addition, PP2A activation by
      formoterol was not antagonized by ICI-118551, and formoterol could activate PP2A
      directly in cell free system. Taken together, formoterol increases corticosteroid
      sensitivity via activation of PP2A in receptor independent manner, explaining its
      benefits as add-on therapy for the treatment of corticosteroid-insensitive
      diseases, such as severe asthma.

PMID- 22401994
TI  - Introduction to the special section: the role of supervision in ensuring the
      development of psychotherapy competencies across diverse theoretical
      perspectives.
AB  - A general overview of the Special Section is presented, beginning with a
      description of its purpose and focus. Next, the articles comprising the Special
      Section are introduced, highlighting the range of theoretical perspectives
      represented and outlining the content areas discussed. The introduction concludes
      with a brief account of the commentary article and its focus.

PMID- 22401995
TI  - Competency in integrative psychotherapy: perspectives on training and
      supervision.
AB  - Increasingly, many psychotherapists identify with an integrative approach to
      psychotherapy. In recent years, more attention has been directed toward the
      operationalization and evaluation of competence in professional psychology and
      health care service delivery. Aspects of integrative psychotherapy competency may
      differ from competency in other psychotherapy orientations, although convergence
      is more often the case. Despite the potential differences, there exist very few
      formal training programs or guidelines to systematically guide clinicians in
      developing a competent integrative practice. This paper attempts to distill the
      essential elements of competent integrative psychotherapy practice and focuses on
      how these might be developed in training and supervision. We address most of
      these complex issues from a specific integrative perspective: principle-based
      assimilative integration.

PMID- 22401996
TI  - Competency in conducting cognitive-behavioral therapy: foundational, functional,
      and supervisory aspects.
AB  - The delivery of cognitive-behavioral therapy (CBT) is described in terms of
      foundational and functional competencies, with additional attention paid to how
      these skills are applied in clinical supervision. Foundational competencies
      include such qualities as ethical behavior, good interpersonal relational skills,
      a healthy capacity for self-awareness and self-correction, cross-cultural
      sensitivity, and an appreciation for the empirical basis of clinical procedures.
      Functional competencies include the ability to think like an empiricist and to
      teach clients to do the same, to conceptualize cases in terms of maladaptive
      beliefs and behavioral patterns, to structure sessions in an organized and time
      effective manner, and to assign and review homework assignments. CBT supervisors
      have the multiple responsibilities of serving as professional role models for
      their supervisees, nurturing the latter's professional development (although also
      being ready to identify and remediate problems in the supervisee's performance),
      and engaging in ongoing self-improvement and education to function most
      effectively as clinical mentors. A brief, descriptive supervisory vignette is
      presented.

PMID- 22401997
TI  - Key competencies of the psychodynamic psychotherapist and how to teach them in
      supervision.
AB  - Four of Rodolfa et al.'s (2005) competencies in professional psychology
      relationship, self-reflection, assessment-case conceptualization, and
      intervention-are key for the psychodynamic psychotherapist. Relationship lies at
      the heart of what is understood to be curative about psychodynamic psychotherapy.
      Self-reflection implies a complex and highly developed process that includes but
      goes beyond Rodolfa et al.'s and Kaslow, Dunn, and Smith's (2008) definitions.
      Competent assessment, diagnosis, and case conceptualization entails making
      inferences about unconscious processes by observing the client and also one's own
      experience, and integrating these inferences with theory. Effective psychodynamic
      intervention is derived from what the psychotherapist has experienced, processed,
      and conceptualized about the relationship with the client and about the client's
      internal object world. An extended vignette shows these competencies emerging in
      a psychotherapist-in-training, facilitated by an intense interaction with a
      supervisor. Although the supervisory and clinical tasks are different, the
      supervisor provides a relationship experience that models these same competencies
      for the supervisee and catalyzes their development in the supervisee.

PMID- 22401998
TI  - Humanistic-existential psychotherapy competencies and the supervisory process.
AB  - There has been an increasing focus in recent years on articulating foundational
      and functional competencies for practice in professional psychology and how a
      competency-based approach might inform psychology training. With the aim of
      contributing to the dialogue in this area, the discussion herein explores
      psychotherapy competencies through the lens of a humanistic-existential
      perspective and describes implications for psychotherapy training and
      supervision. Specifically, competencies pertaining to facilitating the client's
      experiential awareness and use of the psychotherapy relationship to engender
      client change are described. Next, the foundational and functional competencies
      within professional psychology that are particularly salient to a humanistic
      existential psychotherapy framework are discussed. Finally, the ways in which a
      humanistic-existential supervision framework contributes to the development of
      psychotherapy competencies in trainees is considered. A brief vignette is
      presented to illustrate the supervision process.

PMID- 22401999
TI  - A competency-based approach to couple and family therapy supervision.
AB  - The competency-based movement continues to guide professional psychology. This
      has been highlighted through the establishment of essential foundational and
      functional competencies. The current paper focuses on the intervention competency
      domain and delineates its relevance within the field of couple and family therapy
      (CFT). We begin by providing an overview of 8 essential components of CFT:
      developing a systemic formulation, forging a systemic therapeutic alliance,
      understanding family-of-origin issues, reframing, managing negative interactions,
      building cohesion/intimacy/communication, restructuring/parenting, and
      understanding and applying evidence-based CFT models. We then provide a brief
      illustration of foundational and functional competencies essential to CFT. We
      conclude by addressing the CFT competency within an integrative approach to
      supervision and provide a case illustration that depicts this process. The
      relevance of establishing unique, evidence-based, theory-specific competency
      components is highlighted.

PMID- 22402000
TI  - Psychotherapy-based supervision models in an emerging competency-based era: a
      commentary.
AB  - As psychology engages in a cultural shift to competency-based education and
      training supervision practice is being transformed to the use of competency
      frames and the application of benchmark competencies. In this issue,
      psychotherapy-based models of supervision are conceptualized in a competency
      framework. This paper reflects on the translation of key components of each
      psychotherapy-based supervision approach in terms of foundational and functional
      competencies articulated in the Competencies Benchmarks (Fouad et al., 2009). The
      commentary concludes with a discussion of implications for supervision practice
      and identifies directions for future articulation and development, including
      evidence-based psychotherapy supervision.

PMID- 22402001
TI  - Enhancing supervisee reflectivity in clinical supervision: a case study
      illustration.
AB  - Reflectivity has been described as the cyclical process whereby individuals
      engage in a critical evaluation of their affective, cognitive, and behavioral
      experiences to produce insight and fundamental shifts in their original beliefs.
      Developing reflectivity in supervisees is one of the most challenging, yet
      important, responsibilities of clinical supervisors, given its link to such
      skills as critical thinking, ethical decision making, and problem solving. This
      paper advances the literature by presenting a case example that demonstrates how
      reflectivity can be emphasized in clinical supervision, highlighting the barriers
      to reflectivity, and providing strategies that supervisors can utilize to
      encourage reflectivity within clinical supervision. The strategies and
      information discussed may be flexibly applied to supervisees of all developmental
      levels within the context of individual supervision.

PMID- 22402002
TI  - The agonistic metaphor in psychotherapy: should clients battle their blues?
AB  - A tradition stretching back to early Greek philosophy has described the mind as a
      field of struggle or even battle. This comparison has been termed the agonistic
      metaphor, based on the Hellenistic notion of athletic contests. Today, it is not
      uncommon for psychotherapists and the general public to seek solutions to mental
      health problems agonistically. Examples of this are cited from major
      psychodynamic, cognitive, behavioral, family, and humanistic theorists, and
      advantages and disadvantages of the metaphor are explored. Although agonistic
      thinking can energize clients and ennoble the therapeutic journey, it runs the
      risk of ignoring educative aspects of problematic situations and ironically
      perpetuating the resistance it predicts.

PMID- 22402003
TI  - Psychotherapist mindfulness and the psychotherapy process.
AB  - [Correction Notice: An erratum for this article was reported in Vol 47(2) of
      Psychotherapy: Theory, Research & Practice (see record 2010-13424-005). the order
      of authorship and the affiliations of the authors was incorrectly printed. The
      correct order and affiliations are as follows: Noah Bruce, Shauna L. Shapiro,
      Michael J. Constantino, and Rachel Manber; Kaiser Permanente, Santa Clara
      University, University of Massachusetts, Stanford University] A psychotherapist's
      ability to relate to his or her patients is essential for decreasing patient
      suffering and promoting patient growth. However, the psychotherapy field has
      identified few effective means for training psychotherapists in this ability. In
      this conceptual article, we propose that mindfulness practice may be a means for
      training psychotherapists to better relate to their patients. We posit that
      mindfulness is a means of self-attunement that increases one's ability to attune
      to others (in this case, patients) and that this interpersonal attunement
      ultimately helps patients achieve greater self-attunement that, in turn, fosters
      decreased symptom severity, greater well-being, and better interpersonal
      relationships.

PMID- 22402004
TI  - Avoiding the road to ethical disaster: overcoming vulnerabilities and developing
      resilience.
AB  - Psychotherapists may, despite their best intentions, find themselves engaging in
      ethically problematic behaviors that could have been prevented. Drawing on recent
      research in moral psychology and longstanding community mental health approaches
      to prevention, we suggest that psychotherapists can reduce the likelihood of
      committing ethical infractions (and move in the direction of ethical excellence)
      by attending carefully to 4 general dimensions: the desire to facilitate positive
      (good) outcomes, the powerful opportunities given to professionals to effect
      change, personal values, and education. Each dimension can foster enhanced
      ethical behavior and personal resilience, but each can also contribute to ethical
      vulnerability. By recognizing and effectively addressing these dimensions,
      psychotherapists can reduce their vulnerabilities, enhance their resilience,
      reduce the risk of ethical infractions, and improve the quality of their work.

PMID- 22402005
TI  - Application of adult attachment theory to group member transference and the group
      therapy process.
AB  - Although clinical researchers have applied attachment theory to client
      conceptualization and treatment in individual therapy, few researchers have
      applied this theory to group therapy. The purpose of this article is to begin to
      apply theory and research on adult dyadic and group attachment styles to our
      understanding of group dynamics and processes in adult therapy groups. In
      particular, we set forth theoretical propositions on how group members'
      attachment styles affect relationships within the group. Specifically, this
      article offers some predictions on how identifying group member dyadic and group
      attachment styles could help leaders predict member transference within the
      therapy group. Implications of group member attachment for the selection and
      composition of a group and the different group stages are discussed.
      Recommendations for group clinicians and researchers are offered.

PMID- 22402006
TI  - Comparing cognitive behavioral therapy and integrated cognitive behavioral
      therapy/psychodynamic therapy in group treatment for partner violent men.
AB  - This was a pilot study comparing the effectiveness of cognitive-behavioral
      therapy (CBT; n = 18) with integrated CBT and psychodynamic therapy (CBT/PT; n =
      27) in reducing partner violence. The study examined differences between the two
      treatment groups at posttreatment with regard to attachment dimensions,
      interpersonal problems, psychological/behavioral functioning, and general symptom
      and relationship distress. Results indicated that the CBT/PT groups showed
      significantly more improvement than the CBT groups on measures of partner
      violence, attachment, and interpersonal problems at posttreatment. Conversely,
      the CBT groups showed significantly more improvement than the CBT/PT groups on
      measures of psychological/behavioral functioning and general symptom and
      relationship distress. Finally, there was a significant difference between the
      treatment groups on recidivism rate, with the CBT/PT groups having the lowest
      rate.

PMID- 22402007
TI  - Changes in defensive functioning in a case of avoidant personality disorder.
AB  - This case study is based upon data from a male patient with Avoidant Personality
      Disorder who was in psychoanalytic treatment for 5 years. Defense mechanism use
      was assessed by 3 coders using the Defense Mechanisms Rating Scales. Session
      transcripts from intake, each year of therapy, and 1-year follow-up were used for
      the ratings. Over the course of psychoanalysis and follow-up, the patient's
      Overall Defensive Functioning and High-Adaptive defense level use increased and
      his use of the Disavowal defense level and Fantasy decreased. The pattern of
      change throughout treatment was also assessed. The patient's Overall Defensive
      Functioning decreased initially, followed by an increase through year 4. Overall
      Defensive Functioning decreased again prior to termination before increasing to
      its highest level at follow-up. The results demonstrated changes consistent with
      hypotheses and theory, including overall improvement in defensive functioning, an
      initial regression of defensive functioning, decline in functioning immediately
      prior to termination, and continued improvement posttermination. This pattern of
      defense change highlights the importance of assessing defenses in treatment
      research.

PMID- 22402009
TI  - Operational research and MDG tuberculosis control targets.

PMID- 22402010
TI  - As India grows, tuberculosis control must not be left behind.

PMID- 22402011
TI  - Primary bone lymphoma.
AB  - Primary bone lymphoma is a distinct clinical entity that accounts for 5% of extra
      nodal lymphoma. Most patients have diffuse large B-cell lymphoma and present with
      bone pain, a mass or both. The involvement could be in a single focus or
      disseminated. There are no prospective clinical studies in this disease. Patients
      have been treated with radiotherapy, chemotherapy or a combination. There is a
      trend towards improved outcome with combined modality treatment and further
      improvement with the addition of rituximab. Assessment of response may be
      difficult with current imaging techniques. The prognosis of primary bone lymphoma
      is generally good. Here, the current evidence for the optimal treatment of
      primary bone lymphoma is reviewed and questions for future investigation are
      addressed.

PMID- 22402012
TI  - Adaptation of aminoacylation identity rules to mammalian mitochondria.
AB  - Many mammalian mitochondrial aminoacyl-tRNA synthetases are of bacterial-type and
      share structural domains with homologous bacterial enzymes of the same
      specificity. Despite this high similarity, synthetases from bacteria are known
      for their inability to aminoacylate mitochondrial tRNAs, while mitochondrial
      enzymes do aminoacylate bacterial tRNAs. Here, the reasons for non-aminoacylation
      by a bacterial enzyme of a mitochondrial tRNA have been explored. A mutagenic
      analysis performed on in vitro transcribed human mitochondrial tRNA(Asp) variants
      tested for their ability to become aspartylated by Escherichia coli aspartyl-tRNA
      synthetase, reveals that full conversion cannot be achieved on the basis of the
      currently established tRNA/synthetase recognition rules. Integration of the full
      set of aspartylation identity elements and stabilization of the structural tRNA
      scaffold by restoration of D- and T-loop interactions, enable only a partial gain
      in aspartylation efficiency. The sequence context and high structural instability
      of the mitochondrial tRNA are additional features hindering optimal adaptation of
      the tRNA to the bacterial enzyme. Our data support the hypothesis that non
      aminoacylation of mitochondrial tRNAs by bacterial synthetases is linked to the
      large sequence and structural relaxation of the organelle encoded tRNAs, itself a
      consequence of the high rate of mitochondrial genome divergence.

PMID- 22402014
TI  - Assessing toddlers' speech-sound discrimination.
AB  - OBJECTIVE: Valid and reliable methods for assessing speech perception in toddlers
      are lacking in the field, leading to conspicuous gaps in understanding how speech
      perception develops and limited clinical tools for assessing sensory aid benefit
      in toddlers. The objective of this investigation was to evaluate speech-sound
      discrimination in toddlers using modifications to the Change/No-Change procedure
      [1]. METHODS: Normal-hearing 2- and 3-year-olds' discrimination of acoustically
      dissimilar ("easy") and similar ("hard") speech-sound contrasts were evaluated in
      a combined repeated measures and factorial design. Performance was measured in
      d'. Effects of contrast difficulty and age were examined, as was test-retest
      reliability, using repeated measures ANOVAs, planned post hoc tests, and
      correlation analyses. RESULTS: The easy contrast (M=2.53) was discriminated
      better than the hard contrast (M=1.72) across all ages (p<.0001). The oldest
      group of children (M=3.13) discriminated the contrasts better than youngest
      (M=1.04; p<.0001) and the mid-age children (M=2.20; p=.037), who in turn
      discriminated the contrasts better than the youngest children (p=.010). Test
      retest reliability was excellent (r=.886, p<.0001). Almost 90% of the children
      met the teaching criterion. The vast majority demonstrated the ability to be
      tested with the modified procedure and discriminated the contrasts. The few who
      did not were 2.5 years of age and younger. CONCLUSIONS: The modifications
      implemented resulted, at least preliminarily, in a procedure that is reliable and
      sensitive to contrast difficulty and age in this young group of children,
      suggesting that these modifications are appropriate for this age group. With
      further development, the procedure holds promise for use in clinical populations
      who are believed to have core deficits in rapid phonological encoding, such as
      children with hearing loss or specific language impairment, children who are
      struggling to read, and second-language learners.

PMID- 22402015
TI  - Development of an adaptive low-pass filtered speech test for the identification
      of auditory processing disorders.
AB  - OBJECTIVE: One type of test commonly used to examine auditory processing
      disorders (APD) is the low-pass filtered speech test (LPFST), of which there are
      various versions. In LPFSTs, a monaural, low-redundancy speech sample is
      distorted by using filtering to modify its frequency content. Due to the richness
      of the neural pathways in the auditory system and the redundancy of acoustic
      information in spoken language, a normal listener is able to recognize speech
      even when parts of the signal are missing, whereas this ability is often impaired
      in listeners with APD. One limitation of the various versions of the LPFST is
      that they are carried out using a constant level of low-pass filtering (e.g. a
      fixed 1kHz corner frequency) which makes them prone to ceiling and floor effects.
      The purpose of this study was to counter these effects by modifying the LPFST
      using a computer-based adaptive procedure, and to evaluate the performance of
      normal-hearing participants of varying ages on the test. METHODS: In this
      preliminary study, 33 adults and 30 children (aged 8-11 years) with no known
      history of listening difficulties were tested. The University of Canterbury
      Adaptive Speech Test (UCAST) platform was used to administer a four-alternative
      forced-choice adaptive test that altered a low-pass filter (LPF) to track the
      corner frequency at which participants correctly identified a certain percentage
      of the word stimuli. RESULTS: Findings on the University of Canterbury Adaptive
      Speech Test-Filtered Words (UCAST-FW) indicated a significant maturational
      effect. Adult participants performed significantly better on the UCAST-FW in
      comparison to the child participants. The UCAST-FW test was reliable over
      repeated administrations. CONCLUSIONS: An adaptive low-pass filtered speech test
      such as the UCAST-FW is sensitive to maturational changes in auditory processing
      ability.

PMID- 22402016
TI  - Fostering design for avoiding small parts in commonly used objects.
AB  - RATIONALE AND AIM: Injuries due to the accidental ingestion or aspiration of
      small parts have became a matter of interest in the last 30 years, focusing on
      the relationship between a proper prevention and the diminished frequency of
      occurrences. Small parts in commonly used objects represent a large sector of
      potential danger, taking explicit mouthing behavior of children in the first four
      years of life. In this paper the intent is to show the current situation of
      design projects and legislation around the world, meant to avoid the casual
      accidents due to manufacturing reasons. Proposed process and quality control
      standards seek to eliminate production errors and control materials to avoid
      deviation from the design. METHODS: The present study draws its data from the
      Susy Safe registry, a European Commission co-funded project started in February
      2005, whose aim is to establish an international registry of cases of Foreign
      Bodies (FB) injuries in children aged 0-14 years. Information collected from the
      data base concern age and gender of the child, location, shape, volume,
      consistency and elipticity of the foreign body, any complication occurred,
      hospitalization, and behavioral aspects linked to the injury, like the
      supervision of the parents or the activity concomitant to the injury. Cases are
      prospectively collected using the Susy Safe system from 06/2005; moreover, also
      information regarding past consecutive cases available in each center adhering to
      the project have been entered in the Susy Safe Registry. RESULTS: Data evidenced
      that the majority of small parts related injuries are related to stationery. The
      majority of objects (56.7%), were located in the nose, followed by the ears
      (31.5%). The distribution on incidence of FB injuries by age class shows that the
      majority of injuries due to small parts in common objects occurred in children
      older than >3 years. Male and female were affected with the same frequency when
      concerning the nose, while all other locations showed a higher frequency in
      males. Data suggested that hospitalization occurred in 32% of those who compiled
      the form, resulting in complication just in 16% of injured. Although the most
      frequent location needing hospitalization was the tracheobronchial tree, the most
      frequent location showing complication was the nose, 80.3% of the complications,
      having an infection as most frequent outcome. In children younger than 1 year
      median volume reached 333.62 mm(3), in children between 1 and 2 years, median
      volume was 81.12 mm(3), in older children (>3 years) it showed 37.68 mm(3). The
      same considerations can be seen for the ellipticity, where the median ellipticity
      was 2.79 in children <1 year, while it was 1.94 in children between 1 and 2
      years, and 1.17 in the older ones. Consistency is similar for all age classes,
      stressing that rigid small parts were those more involved in injuries with
      foreign bodies. Behavioral aspects pointed out that the 80% of children were
      playing before the accident, and 65.3% were under adults' supervision. Adult
      presence resulted associated to the absence of complication, with a p-value of
      0.04. CONCLUSIONS: The study stresses the importance of primary prevention, seen
      as the active care of adults toward children manipulating foreign bodies
      potentially dangerous. This presence may not avoid the event, but in case of FBs
      aspiration, ingestion, insertion or inhalation, it could be the main factor
      leading to fewer complications.

PMID- 22402017
TI  - Novel deletion mutations of OPTN in amyotrophic lateral sclerosis in Japanese.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by selective motor neuron death in the brain and spinal cord. Many
      disease genes for ALS have been identified; however, each disease gene is
      responsible for very small fractions of ALS. Recently, mutations of the gene
      encoding optineurin (OPTN) are reported in familial and sporadic ALS. OPTN is
      also responsible for a small number of ALS, 3.8% of familial and 0.29% of
      sporadic ALS in Japanese. The low prevalence may be an underestimation due to
      incomplete screening of the mutation. To examine OPTN mutations more extensively,
      we screened the OPTN deletions using a quantitative PCR system. We examined 710
      Japanese ALS subjects who had previously been found to have no OPTN mutations by
      a screening using a PCR-direct sequence strategy. We identified 3 kinds of
      deletions in 5 patients; one was homozygous, and the remaining were heterozygous.
      All deletions occurred due to the Alu-mediated recombination and are expected to
      result in null alleles. Our results suggest that the OPTN deletion mutation in
      ALS is not infrequent and the prevalence of the OPTN mutation in Japanese
      sporadic ALS is considerably high.

PMID- 22402018
TI  - Implication of common and disease specific variants in CLU, CR1, and PICALM.
AB  - Two recent genome-wide association studies (GWAS) for late onset Alzheimer's
      disease (LOAD) revealed 3 new genes: clusterin (CLU), phosphatidylinositol
      binding clathrin assembly protein (PICALM), and complement receptor 1 (CR1). In
      order to evaluate association with these genome-wide association study-identified
      genes and to isolate the variants contributing to the pathogenesis of LOAD, we
      genotyped the top single nucleotide polymorphisms (SNPs), rs11136000 (CLU),
      rs3818361 (CR1), and rs3851179 (PICALM), and sequenced the entire coding regions
      of these genes in our cohort of 342 LOAD patients and 277 control subjects. We
      confirmed the association of rs3851179 (PICALM) (p = 7.4 * 10(-3)) with the
      disease status. Through sequencing we identified 18 variants in CLU, 3 of which
      were found exclusively in patients; 8 variants (out of 65) in CR1 gene were only
      found in patients and the 16 variants identified in PICALM gene were present in
      both patients and controls. In silico analysis of the variants in PICALM did not
      predict any damaging effect on the protein. The haplotype analysis of the
      variants in each gene predicted a common haplotype when the 3 single nucleotide
      polymorphisms rs11136000 (CLU), rs3818361 (CR1), and rs3851179 (PICALM),
      respectively, were included. For each gene the haplotype structure and size
      differed between patients and controls. In conclusion, we confirmed association
      of CLU, CR1, and PICALM genes with the disease status in our cohort through
      identification of a number of disease-specific variants among patients through
      the sequencing of the coding region of these genes.

PMID- 22402019
TI  - Imaging-based assessment of the mineral composition of urinary stones: an in
      vitro study of the combination of hounsfield unit measurement in noncontrast
      helical computerized tomography and the twinkling artifact in color Doppler
      ultrasound.
AB  - We evaluated the value of combining noncontrast helical computerized tomography
      (NCHCT) and color Doppler ultrasound in the assessment of the composition of
      urinary stones. In vitro, we studied 120 stones of known composition, that
      separate into the five main types: 18 calcium oxalate monohydrate (COM) stones,
      41 calcium oxalate dihydrate (COD) stones, 24 uric acid stones, 25 calcium
      phosphate stones and 12 cystine calculi. Stones were characterized in terms of
      their Hounsfield density (HU) in NCHCT and the presence of a twinkling artifact
      (TA) in color Doppler ultrasound. There were statistically significant HU
      differences between calcium and non-calcium stones (p < 0.001), calcium oxalate
      stones and calcium phosphate stones (p < 0.001) and uric acid stones and cystine
      calculi (p < 0.001) but not between COM and COD stones (p = 0.786). Hence, the HU
      was a predictive factor of the composition of all types of stones, other than for
      COM and COD stones within the calcium oxalate class (p > 0.05). We found that the
      TA does not enable differentiation between calcium and non-calcium stones (p >
      0.999), calcium oxalate stones and calcium phosphate stones (p = 0.15), or uric
      acid stones and cystine calculi (p = 0.079). However, it did reveal a significant
      difference between COM and COD stones (p = 0.002). The absence of a TA is a
      predictive factor for the presence of COM stones (p = 0.008). Hence, the
      association of NCHCT and Doppler enables the accurate classification of the five
      types of stones in vitro.

PMID- 22402020
TI  - Evaluation of methods for sizing and counting of ultrasound contrast agents.
AB  - A precise, accurate and well documented method for the sizing and counting of
      microbubbles is essential for all aspects of quantitative microbubble-enhanced
      ultrasound imaging. The efficacy of (a) electro-impedance volumetric zone sensing
      (ES) also called a Coulter counter/multisizer; (b) optical microscopy (OM); and
      (c) laser diffraction (LD), for the sizing and counting of microbubbles was
      assessed. Microspheres with certified mean diameter and number concentration were
      used to assess sizing and counting reproducibility (precision) and reliability
      (accuracy) of ES, OM and LD. SonoVueTM was repeatedly (n = 3) sized and counted
      to validate ES, OM and LD sizing and counting efficacy. Statistical analyses of
      intra-method variability for the SonoVueTM mean diameter showed that the best
      microbubble sizing reproducibility was obtained using OM with a mean diameter
      sizing variability of 1.1%, compared with a variability of 4.3% for ES and 7.1%
      for LD. The best microbubble counting reproducibility was obtained using ES with
      a number concentration variability of 8.3%, compared with a variability of 22.4%
      for OM and 32% for LD. This study showed that no method is fully suited to both
      sizing and counting of microbubbles.

PMID- 22402021
TI  - Muscle crush injury of extremity: quantitative elastography with supersonic shear
      imaging.
AB  - The aim of this study was to determine the characteristic of muscle crush injury
      at quantitative ultrasonographic elastography using supersonic shear imaging
      (SSI). Twenty-three New Zealand rabbits underwent crush injury to left hind leg
      caused by a special balloon cuff device. Conventional ultrasonography and SSI
      quantitative elastography were performed at both crushed and uncrushed regions of
      the left hind legs. Quantitative lesion elasticity was measured using the Young's
      modulus (in kilopascals) at 0.5 h, 2 h, 6 h, 24 h and 72 h after the release of
      the crushing pressure. Compared with those from the uncrushed regions, both the
      maximum and mean elasticity values at these time points from the crushed regions
      were significantly higher (p < 0.001). A receiver operating characteristic (ROC)
      analysis was employed to assess diagnostic performance. ROC curves showed that
      extremity crush injury was diagnosed using elasticity value and the greater the
      elasticity value, the greater the diagnostic value. SSI provides quantitative
      elasticity measurements, thus, adding complementary information that potentially
      could help in crush injury characterization with conventional ultrasonography.

PMID- 22402022
TI  - Sizing gaseous emboli using Doppler embolic signal intensity.
AB  - Extension of transcranial Doppler embolus detection to estimation of bubble size
      has historically been hindered by difficulties in applying scattering theory to
      the interpretation of clinical data. This article presents a simplified approach
      to the sizing of air emboli based on analysis of Doppler embolic signal
      intensity, by using an approximation to the full scattering theory that can be
      solved to estimate embolus size. Tests using simulated emboli show that our
      algorithm is theoretically capable of sizing 90% of "emboli" to within 10% of
      their true radius. In vitro tests show that 69% of emboli can be sized to within
      20% of their true value under ideal conditions, which reduces to 30% of emboli if
      the beam and vessel are severely misaligned. Our results demonstrate that
      estimation of bubble size during clinical monitoring could be used to distinguish
      benign microbubbles from potentially harmful macrobubbles during intraoperative
      clinical monitoring.

PMID- 22402023
TI  - Simulation model for assessing quality of ultrasound strain estimation in
      abdominal aortic aneurysm.
AB  - The purpose of this study was to develop a simulation model for evaluating
      methods for ultrasound strain estimation in abdominal aortic aneurysms. Wall
      geometry was obtained from a real ultrasound image and wall motion was simulated
      applying realistic blood pressures to a nonlinear viscoelastic wall model. The
      ultrasound simulation included speckle, absorption and angle dependent
      reflection. Gaussian white noise was added to simulate various noise levels.
      Despite not fully replicating real ultrasound images, the model simulated
      realistic circumferential variations in intensity and realistic speckle patterns
      and has potential for initial evaluation of strain estimation methods.

PMID- 22402024
TI  - Investigating the subharmonic response of individual phospholipid encapsulated
      microbubbles at high frequencies: a comparative study of five agents.
AB  - There are a range of contrast ultrasound applications above 10 MHz, a frequency
      regime in which nonlinear microbubble behavior is poorly understood. Lipid
      encapsulated microbubbles have considerable potential for use at higher
      frequencies because they have been shown to exhibit pronounced nonlinear activity
      at frequencies up to 40 MHz. The objective of this work was to investigate the
      influence of agent formulation on the subharmonic response of lipid-encapsulated
      microbubbles at high frequencies with a view to providing information relevant to
      improving contrast agent design and imaging performance. An optical-acoustical
      setup was used to measure the subharmonic emissions from small (d < 3 MUm)
      individual lipid-encapsulated microbubbles as a function of transmit pressure,
      size and composition. In this study, five agent formulations (DefinityTM,
      MicroMarkerTM and three in-house agents manipulated to exhibit different levels
      of shell microstructure heterogeneity) were insonified at 25 MHz over a peak
      negative pressure (P(n)) range of 0.02-1.2 MPa. All agents exhibited distinctly
      different subharmonic behavior, both in terms of amplitude and active sizes.
      MicroMarkerTM exhibited the strongest, broadest and most consistent subharmonic
      response, 22% greater in power than that of DefinityTM and as much as 50% greater
      than the in-house formulations. No clear relation between in-house agents' shell
      microstructure and nonlinear response was found, other than the variability in
      the nonlinear response itself. An analysis of the response of MicroMarkerTM
      bubbles suggests that these bubbles exhibit "expansion-dominated" oscillations,
      in contrast to "compression-only" oscillations observed for similar bubbles at
      lower frequencies (f < 11 MHz).

PMID- 22402025
TI  - An efficient treatment strategy for histotripsy by removing cavitation memory.
AB  - Cavitation memory effects occur when remnants of cavitation bubbles (nuclei)
      persist in the host medium and act as seeds for subsequent events. In pulsed
      cavitational ultrasound therapy, or histotripsy, this effect may cause cavitation
      to repeatedly occur at these seeded locations within a target volume, producing
      inhomogeneous tissue fractionation or requiring an excess number of pulses to
      completely homogenize the target volume. We hypothesized that by removing the
      cavitation memory, i.e., the persistent nuclei, the cavitation bubbles could be
      induced at random locations in response to each pulse; therefore, complete
      disruption of a tissue volume may be achieved with fewer pulses. To test the
      hypothesis, the cavitation memory was passively removed by increasing the
      intervals between successive pulses, ?t, from 2, 10, 20, 50 and 100, to 200 ms.
      Histotripsy treatments were performed in red blood cell tissue phantoms and ex
      vivo livers using 1-MHz ultrasound pulses of 10 cycles at P-/P+ pressure of 21/59
      MPa. The phantom study allowed for direct visualization of the cavitation
      patterns and the lesion development process in real time using high-speed
      photography; the ex vivo tissue study provided validation of the memory effect in
      real tissues. Results of the phantom study showed an exponential decrease in the
      correlation coefficient between cavitation patterns in successive pulses from 0.5
      +/- 0.1 to 0.1 +/- 0.1 as ?t increased from 2-200 ms; correspondingly, the lesion
      was completely fractionated with significantly fewer pulses for longer ?ts. In
      the tissue study, given the same number of therapy pulses, complete and
      homogeneous tissue fractionation with well-defined lesion boundaries was achieved
      only for ?t >= 100 ms. These results indicated that the removal of the cavitation
      memory resulted in more efficient treatments and homogeneous lesions.

PMID- 22402026
TI  - Nanoparticle delivery for metastatic breast cancer.
AB  - Breast cancer represents a major ongoing public health problem as the most common
      non-cutaneous malignancy among U.S. women. While significant progress has been
      made in improving loco-regional treatments for breast cancer, relatively little
      progress has been made in diagnosing and treating patients with metastatic breast
      cancer. At present there are limited curative options for patients with breast
      cancer metastatic beyond regional nodes. Emerging nanotechnologies promise new
      approaches to early detection and treatment of metastatic breast cancer.
      Fulfilling the promise of nanotechnologies for patients with metastatic breast
      cancer will require delivery of nanomaterials to sites of metastatic disease.
      Future translational approaches will rely on an ever increasing understanding of
      the biology of breast cancer subtypes and their metastases. These important
      concepts will be highlighted and elucidated in this manuscript.

PMID- 22402027
TI  - Magnetic nanovectors for drug delivery.
AB  - Nanotechnology holds the promise of novel and more effective treatments for
      vexing human health issues. Among these are the use of nanoparticle platforms for
      site-specific delivery of therapeutics to tumors, both by passive and active
      mechanisms; the latter includes magnetic vectoring of magnetically responsive
      nanoparticles (MNP) that are functionalized to carry a drug payload that is
      released at the tumor. The conceptual basis, which actually dates back a number
      of decades, resides in physical (magnetic) enhancement, with magnetic field
      gradients aligned non-parallel to the direction of flow in the tumor vasculature,
      of existing passive mechanisms for extravasation and accumulation of MNP in the
      tumor interstitial fluid, followed by MNP internalization. In this review, we
      will assess the most recent developments and current status of this approach,
      considering MNP that are composed of one or more of the three elements that are
      ferromagnetic at physiological temperature: nickel, cobalt and iron. The effects
      on cellular functions in vitro, the ability to successfully vector the platform
      in vivo, the anti-tumor effects of such localized nano-vectors, and any
      associated toxicities for these MNP will be presented. The merits and
      shortcomings of nanomaterials made of each of the three elements will be
      highlighted, and a roadmap for moving this long-established approach forward to
      clinical evaluation will be put forth.

PMID- 22402028
TI  - Factors associated with lack of awareness and uncontrolled high blood pressure
      among Canadian adults with hypertension.
AB  - BACKGROUND: Approximately 17% of Canadians with high blood pressure were unaware
      of their condition, and of Canadians aware of having the condition, approximately
      1 in 5 have uncontrolled high blood pressure despite high rates of
      pharmacotherapy. The objectives of the current study are to estimate the
      prevalence of resistant hypertension and examine factors associated with (1) lack
      of awareness and (2) uncontrolled hypertension despite pharmacotherapy. METHODS:
      Using the 2007-2009 Canadian Health Measures Survey (N = 3473, aged 20-79 years)
      and logistic regression, we quantified relationships between characteristics and
      (1) presence of hypertension, (2) lack of awareness (among those with
      hypertension), and (3) uncontrolled high blood pressure (among those treated for
      hypertension). RESULTS: Older age, lowest income, and less than high school
      education were associated with presence of hypertension. Men (odds ratio [OR],
      1.6; 95% confidence interval [CI], 1.1-2.2) and adults < 60 years (OR, 1.7; 95%
      CI, 1.1-2.6) were more likely than others to be unaware. Among those aged 60+
      years, women were more likely than men to have uncontrolled high blood pressure
      (OR, 2.4; 95% CI, 1.1-5.2) despite treatment. Elevated systolic blood pressure
      was the issue in over 90% of women and 80% of men with uncontrolled hypertension.
      Depending on the definition employed, 4.4% (95% CI, 2.4-6.4) to 7.8% (95% CI, 6.0
      9.6) of the population with hypertension had resistant hypertension. CONCLUSIONS:
      Messaging or interventions encouraging screening may be helpful for all younger
      Canadian adults and men; programs encouraging blood pressure control may help
      older women.

PMID- 22402029
TI  - A comparison of low- and high-impact forced exercise: effects of training
      paradigm on learning and memory.
AB  - In this study we compared two types of forced exercise-a low impact paradigm to
      minimize stress, which included speeds up to 10 m/min and a stressful high impact
      paradigm, with speeds up to 21 m/min. 150 male C57BL/6J mice were randomly
      assigned to the low impact, high impact, or sedentary control conditions and were
      tested on the rotorod and Morris water maze (MWM) as indices of motor learning
      and spatial memory. We found that 5 weeks of stressful high speed forced exercise
      led to significant improvement in rotorod performance, as high impact runners
      outperformed both low impact runners and controls at 15 and 25 rpm speeds. These
      differences were the result of improved physical fitness due to exercise and
      likely do not reflect enhanced learning in these mice. In the MWM, 5 weeks of
      stressful high impact exercise led to significant impairment in spatial memory
      acquisition compared to low impact runners and controls. Low impact exercise for
      10 weeks significantly improved retention of spatial memory compared to high
      impact exercise. Results suggested that these two paradigms produced different
      effects of forced exercise on learning and memory. The low impact paradigm led to
      some improvements, whereas the stressful high impact program caused significant
      impairment. Comparison of these two paradigms begins to address the window
      between the beneficial and detrimental effects of forced exercise, and have
      suggested a boundary of exercise intensity that leads to impairment in learning.

PMID- 22402030
TI  - Noise exposure enhances auditory cortex responses related to hyperacusis
      behavior.
AB  - Hyperacusis, a marked intolerance to normal environmental sound, is a common
      symptom in patients with tinnitus, Williams syndrome, autism, and other
      neurologic diseases. It has been suggested that an imbalance of excitation and
      inhibition in the central auditory system (CAS) may play an important role in
      hyperacusis. Recent studies found that noise exposure, one of the most common
      causes of hearing loss and tinnitus, can increase the auditory cortex (AC)
      response, presumably by increasing the gain of the AC. However, it is not clear
      whether the increased cortical response will affect sound sensitivity and induce
      hyperacusis. In this experiment, we studied the effects of noise exposure (narrow
      band noise, 12 kHz, 120 dB SPL, 1 hour) on the physiological response of the
      inferior colliculus (IC) and the AC, and the behavioral sound reaction in
      conscious Sprague Dawley rats. Noise exposure induced a decrease of sound evoked
      potential in the IC. However, significant increases of AC response including
      sound evoked potentials and the spike firing rates of AC neurons were recorded
      right after the noise exposure. These results suggest that noise exposure induces
      hyperexcitability of AC presumably by increasing the post-synaptic response of AC
      neurons. The behavioral consequence of the noise exposure on sound perception was
      measured by the amplitude of the acoustic startle response before and after noise
      exposure in a separate group of rats. Although noise exposure caused a moderate
      hearing loss, the acoustic startle amplitude at the super-threshold level was
      significantly increased. These results suggest that noise exposure can cause
      exaggerated the sound reaction which may be related with the enhanced
      responsiveness of the AC neurons. This phenomenon may be related with noise
      induced hyperacusis.This article is part of a Special Issue entitled: Tinnitus
      Neuroscience.

PMID- 22402032
TI  - Effect of cytoskeletal elastic properties on the mechanoelectrical transduction
      in excitable cells.
AB  - This paper addresses the possible mechanism of stretch on cell electrochemical
      potential change, based on the physicochemical properties of cytoskeletal
      network. Synthetic polyelectrolyte gel was used as an experimental model of the
      cytoskeleton. Gel samples with different density of network cross linking were
      studied. Triangular axial deformations of samples were applied. Simultaneously,
      the electrochemical (Donnan) potential of the gel was measured between a
      micropipette electrode pinned into the swollen gel, and a reference electrode in
      the outer solution. We found that axial deformation shifts the gel potential
      toward depolarization. The extent of gel depolarization showed a close negative
      correlation with the Young modulus of the gel. We suggest that the underlying
      mechanism is likely to be a universal process of counterion adsorption on charged
      polymer filaments due to the decrease of distance between polymer filaments owing
      to gel elongation.

PMID- 22402031
TI  - BK polyomavirus: emerging pathogen.
AB  - BK polyomavirus (BKPyV) is a small double-stranded DNA virus that is an emerging
      pathogen in immunocompromised individuals. BKPyV is widespread in the general
      population, but primarily causes disease when immune suppression leads to
      reactivation of latent virus. Polyomavirus-associated nephropathy and hemorrhagic
      cystitis in renal and bone marrow transplant patients, respectively, are the most
      common diseases associated with BKPyV reactivation and lytic infection. In this
      review, we discuss the clinical relevance, effects on the host, virus life cycle,
      and current treatment protocols.

PMID- 22402033
TI  - Long-term dynamic profiling of inflammatory mediators in double-hit burn and
      sepsis animal models.
AB  - Burn injuries together with its subsequent complications, mainly bacterial
      infections originating from gastrointestinal tract, activate the host immune
      system through stimulation of a series of local and systemic responses, including
      the release of inflammatory mediators. To gain a more comprehensive understanding
      of these complex physiological changes and to propose therapeutic approaches to
      combat the deleterious consequences of burn and septic shocks, it is essential to
      analyze animal models of burn and sepsis. In this study, we analyzed the long
      term profiles of cytokines and chemokines in rat models which received burn
      injury followed 2 days later by cecal ligation and puncture (CLP) to induce
      sepsis and were sacrificed at different time points within 10 days (0, 1, 2, 3,
      4, 7 and 10 days). It was observed that MCP-1 concentrations were elevated in all
      animal models following the burn injury or CLP treatment. IP-10 concentration was
      persistently decreased after CLP or sham-CLP treatments. GRO/KC concentration was
      also increased following the burn injury and CLP. It was elucidated that, in more
      severe injury model which received both burn and CLP treatments, GMCSF and MIP
      1alpha (chemokines), IL-1alpha (a pro-inflammatory cytokine) and IL-6 (exhibiting
      both pro- and anti-inflammatory behaviors) were upregulated on the 7th and 10th
      days, which might be to protect the host system from the subsequent complications
      caused by burn and sepsis. In order to elucidate critical regulatory
      interactions, putative transcription factors of the inflammatory mediators which
      have been significantly changed following the injuries were further identified by
      analyzing the conserved regions of the promoters of cytokines and chemokines. In
      conclusion, the long term profiles of the inflammatory mediators were profoundly
      characterized in this study to gain a comprehensive understanding of inflammatory
      mediators' behaviors in various injury models.

PMID- 22402034
TI  - Role of the OPG/RANK/RANKL triad in calcifications of the atheromatous plaques:
      comparison between carotid and femoral beds.
AB  - Recent works demonstrated the difference of calcification genesis between carotid
      and femoral plaques, femoral plaques being more calcified. It has been clearly
      demonstrated that the molecular triad osteoprotegerin (OPG)/Receptor Activator of
      NFkB (RANK)/RANK Ligand (RANKL) exerts its activities in the osteoimmunology and
      vascular system. The aim of this study was to determine their expression and
      their potential role in calcifications of the atheromatous plaques located in two
      different peripheral arterial beds, carotid and femoral. The expression of OPG,
      RANK and RANKL was analyzed by immunochemistry in 40 carotid and femoral samples.
      Blood OPG and RANKL were quantified using specific ELISA assays. OPG staining was
      more frequently observed in carotid than in femoral plaques, especially in lipid
      core. Its expression correlated with macrophage infiltration more abundantly
      observed in carotid specimens. Surprisingly, serum OPG concentration was
      significantly lower in carotid population compared to femoral population while
      RANK and RANKL were equally expressed in both arterial beds. Carotid plaques that
      are less rich in calcium than femoral specimens, express more frequently OPG,
      this expression being correlated with the abundance of macrophages in the
      lesions. These data strengthen the key role played by OPG in the differential
      calcification in carotid and femoral plaques.

PMID- 22402036
TI  - SigH, antioxidants, and the pathogenesis of pulmonary tuberculosis.

PMID- 22402035
TI  - The Mycobacterium tuberculosis stress response factor SigH is required for
      bacterial burden as well as immunopathology in primate lungs.
AB  - BACKGROUND: Sigma H (sigH) is a major Mycobacterium tuberculosis (Mtb) stress
      response factor. It is induced in response to heat, oxidative stress, cell wall
      damage, and hypoxia. Infection of macrophages with the Delta-sigH mutant
      generates more potent innate immune response than does infection with Mtb. The
      mutant is attenuated for pathology in mice. METHODS: We used a nonhuman primate
      (NHP) model of acute tuberculosis, to better understand the phenotype of the
      Delta-sigH mutant in vivo. NHPs were infected with high doses of Mtb or the
      mutant, and the progression of tuberculosis was analyzed in both groups using
      clinical, pathological, microbiological, and immunological parameters. RESULTS:
      Animals exposed to Mtb rapidly progressed to acute pulmonary tuberculosis as
      indicated by worsening clinical correlates, high lung bacterial burden, and
      granulomatous immunopathology. All the animals rapidly succumbed to tuberculosis.
      On the other hand, the NHPs exposed to the Mtb:Delta-sigH mutant did not exhibit
      acute tuberculosis, instead showing significantly blunted disease. These NHPs
      survived the entire duration of the study. CONCLUSIONS: The Mtb:Delta-sigH mutant
      is completely attenuated for bacterial burden as well as immunopathology in NHPs.
      SigH and its regulon are required for complete virulence in primates. Further
      studies are needed to identify the molecular mechanism of this attenuation.

PMID- 22402039
TI  - The diversity status of the psychotherapist: editorial introduction.
AB  - During the past decade or so, the multicultural or diversity movement in the
      United States has begun to deeply affect psychotherapy. Too often, authors
      admonished readers to pay more attention to, for example, racial and ethnic
      factors when working with racial/ethnic minority patients without sharing what
      actually happened in the treatment with actual cases. We also seem to equate
      multicultural psychotherapy with the patient's minority or diversity status,
      seeming to forget that the therapist's diversity status is also a key element of
      the treatment process. The psychotherapist/scholars that make up the authors in
      this special section address four topics. They were asked to provide (1) a
      description of their diversity status, (2) key clinical issues raised for them as
      psychotherapists, given their diversity status, (3) key clinical issues raised
      for their patients given their diversity status, and (4) effective treatment
      strategies for addressing their diversity status and its impact on the treatment.
      (PsycINFO Database Record (c) 2010 APA, all rights reserved).

PMID- 22402037
TI  - Clinical evaluation of safety and immunogenicity of PADRE-cytomegalovirus (CMV)
      and tetanus-CMV fusion peptide vaccines with or without PF03512676 adjuvant.
AB  - BACKGROUND: It has been reported that cytomegalovirus (CMV) pp65-specific T cells
      can protect hematopoietic cell transplant (HCT) recipients from CMV
      complications. Two candidate CMV peptide vaccines composed of the HLA A*0201
      pp65(495-503) cytotoxic CD8(+) T-cell epitope fused to 2 different universal T
      helper epitopes (either the synthetic Pan DR epitope [PADRE] or a natural Tetanus
      sequence) were clinically evaluated for safety and ability to elicit pp65 T cells
      in HLA A*0201 healthy volunteers. METHODS: Escalating doses (0.5, 2.5, 10 mg) of
      PADRE or Tetanus pp65(495-503) vaccines with (30 adults) or without (28 adults)
      PF03512676 adjuvant were administered by subcutaneous injection every 3 weeks for
      a total of 4 injections. RESULTS: No serious adverse events were reported,
      although vaccines used in combination with PF03512676 had enhanced
      reactogenicity. Ex vivo responses were detected by flow cytometry exclusively in
      volunteers who received the vaccine coadministered with PF03512676. In addition,
      using a sensitive in vitro stimulation system, vaccine-elicited pp65(495-503) T
      cells were expanded in 30% of volunteers injected solely with the CMV peptides
      and in all tested subjects receiving the vaccines coinjected with PF03512676.
      CONCLUSIONS: Acceptable safety profiles and vaccine-driven expansion of pp65(495
      503) T cells in healthy adults support further evaluation of CMV peptide vaccines
      combined with PF03512676 in the HCT setting. CLINICAL TRIALS REGISTRATION:
      NCT00722839.

PMID- 22402038
TI  - Perspectives on introduction and implementation of new point-of-care diagnostic
      tests.
AB  - In recent years, there has been significant investment from both the private and
      public sectors in the development of diagnostic technologies to meet the need for
      human immunodeficiency virus (HIV) and tuberculosis testing in low-resource
      settings. Future investments should ensure that the most appropriate technologies
      are adopted in settings where they will have a sustainable impact. Achieving
      these aims requires the involvement of many stakeholders, as their needs,
      operational constraints, and priorities are often distinct. Here, we discuss
      these considerations from different perspectives representing those of various
      stakeholders involved in the development, introduction, and implementation of
      diagnostic tests. We also discuss some opportunities to address these
      considerations.

PMID- 22402040
TI  - When hearing clients work with a deaf therapist.
AB  - Not being able to hear can present significant challenges for the therapist and
      for the deaf therapist/hearing client dyad. It can also create opportunities.
      Although the literature indicates that most culturally Deaf therapists work with
      Deaf clients due to their mutual use of American Sign Language, I describe (a)
      the background of an audiologically deaf therapist who relies on speech reading
      rather than sign language, and (b) this therapist's clinical work with hearing
      clients. Some of the relational dynamics of these treatments are identified, and
      I conclude by noting how attention to communication can benefit the work of all
      psychotherapists.

PMID- 22402041
TI  - Perspectives of an Iranian psychologist practicing in America.
AB  - My experience as a male psychologist who was born and raised in Iran has had a
      tremendous impact on my professional practice in the United States. After
      providing a brief history of Iran to put this article in context, I explore 5
      elements of that impact: Description of my diversity status, key practice issues
      raised for me as an Iranian therapist, my background and its impact on case
      formulation, key clinical issues raised for my clients given my diversity status,
      and effective strategies for addressing my diversity status and its impact on the
      treatment.

PMID- 22402042
TI  - On being a Latina healer: voice, consciousness, and identity.
AB  - A Latina psychotherapist relates her journey of becoming a healer. I discuss how
      my diversity status impacts on my life and on my approach to psychotherapy. My
      story offers clinical suggestions for therapists working with multicultural
      clients.

PMID- 22402044
TI  - Cultural influences on the process of conducting psychotherapy: personal
      reflections of an ethnic minority psychologist.
AB  - I was asked to reflect how being a member of an ethnically diverse minority
      group, that is, Japanese American, may have influenced my clinical practice as a
      psychologist and psychotherapist. I first define the various facets of my
      "diversity status," followed by an offering of reflections on how being a member
      of this group impacted both myself as a therapist and my clients. I conclude with
      several general recommendations geared to enhance a positive therapeutic alliance
      and client outcome.

PMID- 22402045
TI  - Reflections of a gay male psychotherapist.
AB  - Issues of diversity and multiculturalism are typically framed and conceptualized
      in terms of client characteristics. This is reflected in the literature on
      competent and ethical treatment of lesbian, gay, bisexual, and transgender (LGBT)
      individuals. However, when it comes to personal characteristics of the therapists
      involved, little has been written, save the obvious proscriptions against
      personal bias and misinformation in conducting psychotherapy. This article
      represents the personal reflections and feelings of a European American gay male
      psychologist with 30 years' experience working with the LGBT community.
      Intersections of sexual orientation and gender identity with race/ethnicity, age,
      health factors, and socioeconomic status are explored as the effects of therapist
      characteristics on the therapeutic process are considered. Observations about
      client differences, as well as therapist differences, are made in such a way that
      the reader might extrapolate to his or her own practice.

PMID- 22402046
TI  - Diversity within African American, female therapists: variability in clients'
      expectations and assumptions about the therapist.
AB  - Despite the presence of some literature that has addressed the characteristics of
      the African American female therapist, most psychotherapy training proceeds with
      the assumption that therapists are members of dominant groups, and most of the
      psychological and psychotherapy literature has been written by therapists and
      psychologists who come from dominant cultural perspectives. Not as much has been
      written about psychological paradigms or the process of psychotherapy from the
      perspective of the therapist who is not a dominant group member. This article
      explores both the common and divergent experiences that we, the authors, share as
      African American female therapists and the different reactions we frequently
      elicit in clients. We also explore how individual differences in our physical
      appearances, personal backgrounds, and different characteristics of our
      respective practices elicit distinct responses from clients that we believe are
      based on differences between us, despite the fact that we are both African
      American women. We believe that many of the stereotypes that affect perceptions
      of African American female clients also exist for African American female
      therapists. We will address how the intersection of gender, race, and sexual
      orientation of the client highlights the complexity of culturally competent
      practice.

PMID- 22402047
TI  - Changes in trainees' intention use and volunteer clients' evaluations of sessions
      during early skills training.
AB  - Volunteer clients (N = 96) evaluated sessions conducted by prepracticum trainees
      prior to and after the trainees received instruction in interpersonal
      psychodynamic therapy. The relationship between changes in therapeutic style,
      measured by intension use, and changes in volunteer clients' session evaluations
      were examined with growth curve analyses. After training, trainees increased
      their focus on client emotions and on the therapeutic relationship and decreased
      their verbal activity. Increased session smoothness was related to decreases in
      trainee verbal activity and to increases in trainee flexibility. Increases in
      volunteer clients' perceptions of trainee expertness, attractiveness, and
      trustworthiness were related to trainees' increased focus on client emotions and
      increased focus on the therapeutic relationship and to decreases in
      confrontation.

PMID- 22402048
TI  - Representations of the supervisory dialogue and the development of
      psychotherapists.
AB  - The primary aim of this study was to investigate the ways in which therapists-in
      training construct and use mental representations of their relationships with
      their supervisors in the service of their own professional development. A total
      of 115 trainees (75% of whom were psychodynamically oriented) completed The
      Supervisory Representation Inventory, a network of measures designed to assess
      the forms, functions, and phenomenological properties of internalized
      representations of that relationship. Results indicate that supervisees tend to
      evoke representations of their supervisors' spoken words, vocal qualities, and
      the settings in which they have met; that they evoke these representations to
      better formulate clinical interventions, especially those perceived as painful or
      difficult for patients to hear; and that these representations are especially
      likely to occur when patients behave in ways consistent with a supervisor's view
      or, when the supervisee is alone and thinking about a patient that has been
      discussed in supervision. Findings support the hypothesis that representations of
      the verbal and nonverbal aspects of the supervisory dialogue play an integral
      role in the acquisition of the skills and professional identity of a
      psychotherapist.

PMID- 22402049
TI  - Therapists' attributions for client premature termination: are they self-serving?
AB  - We conducted two studies of therapist responses to client premature termination
      from psychotherapy. In Study 1, we surveyed therapists' attributions for client
      premature termination from therapy using an open response format. Results
      suggested that therapists showed a self-serving pattern in their attributions
      (i.e., attributed causality to the client or environment) when considering their
      own clients compared to when they considered the premature terminations of
      clients in general. Study 2 was a vignette study in which therapists responded to
      one of two client presentations that varied relationship to client (your client
      vs. other's client). Using the attributional categories derived from Study 1,
      therapists rated the likelihood that each attribution caused the client's
      premature termination. Again, patterns across groups indicated that therapists
      are self-serving in their attributions for client premature termination. In
      addition, differences were found across gender and theoretical orientation;
      larger effects were found for men compared to women, and psychoanalytic
      therapists compared to cognitive-behavioral.

PMID- 22402050
TI  - Applications of the psychotherapy phase model to clinically significant
      deterioration.
AB  - While previous research on deterioration has focused on identifying individuals
      at risk for negative outcomes, little is known about the nature or pattern by
      which deterioration occurs. The problem of deterioration is especially salient in
      training clinics; a setting in which higher deterioration rates have been
      reported. Two studies were designed to test the applicability of the phase model
      to deterioration in a training clinic and to replicate the model with a training
      clinic referral-base sample. In Study 1, the course of therapy was monitored for
      135 clients. For the 38 clients who deteriorated during therapy, a model where
      increased symptoms (demediation) reliably preceded both decreased functioning
      (dehabilitation) and decreased well-being (demoralization) was found. In Study 2,
      the same three phases were prospectively monitored for 914 undergraduate students
      on a weekly basis throughout a single semester. For the 158 individuals who
      deteriorated during this time, a model where demediation reliably preceded
      dehabilitation, which preceded demoralization was found. These results have
      clinical implications for the use of tailored intervention strategies focusing on
      the deterioration phases.

PMID- 22402051
TI  - Shared traumatic reality in communal disasters: toward a conceptualization.
AB  - The phenomenon variously termed "shared reality," "shared trauma," or "shared
      traumatic reality" refers to situations in which helper and helpee,
      psychotherapist and client, are exposed to the same communal disaster. This
      article has two aims. One, pursued in the first part of the article, is to trace
      the development of the concept; analyze the conditions under which it was
      acknowledged, articulated, and labeled; and review the changes in the term over
      time. The other, pursued in the second part, is to offer a conceptualization of
      the phenomenon based on analysis of the literature. Here, the article shows that
      the phenomenon is characterized by two distinct dynamics, one pertaining to
      professionals providing help in the emergency phase, the other to professionals
      conducting ongoing psychotherapy; to offer a preliminary definition of the
      phenomenon which covers the shared features of the two dynamics; and to present
      the distinct features of each.

PMID- 22402052
TI  - What do psychotherapists really do in practice? An Internet study of over 2,000
      practitioners.
AB  - Over 2,200 North American psychotherapists completed a Web-based survey
      concerning their clinical work, including theoretical orientation, client
      characteristics, and use of specific psychotherapy techniques. Psychotherapeutic
      integration was common, with the majority of respondents identifying with more
      than one theoretical orientation or as having an eclectic orientation. The modal
      patient was a White female adult suffering from a mood or anxiety disorder and
      interpersonal problems. Individual psychotherapy was the preferred treatment
      modality. The most frequently endorsed techniques were relationship-oriented such
      as conveying warmth, acceptance, understanding, and empathy. The least frequently
      endorsed techniques were biofeedback, neurofeedback, body and energy therapies,
      and hypnotherapy. Efforts to disseminate empirically based therapies require
      understanding and accommodating clinicians' tendencies to integrate techniques.

PMID- 22402055
TI  - Rivaroxaban and recurrent stroke prevention in AF.

PMID- 22402057
TI  - Proteomics and gene expression analyses of mitochondria from squalene-treated
      apoE-deficient mice identify short-chain specific acyl-CoA dehydrogenase changes
      associated with fatty liver amelioration.
AB  - Squalene, a hydrocarbon involved in cholesterol biosynthesis, is an abundant
      component in virgin olive oil. Previous studies showed that its administration
      decreased atherosclerosis and steatosis in male apoE knock-out mice. To study the
      effect of squalene on mitochondrial proteins in fatty liver, 1 g/kg/day of this
      isoprenoid was administered to those mice. After 10 weeks, hepatic fat was
      assessed and protein extracts from mitochondria enriched fractions from control
      and squalene-treated animals were analyzed by 2D-DIGE. Spots exhibiting
      significant differences were identified by MS analysis. Squalene administration
      modified the expression of eighteen proteins involved in different metabolic
      processes, 12 associated with hepatic fat content. Methionine adenosyltransferase
      I alpha (Mat1a) and short-chain specific acyl-CoA dehydrogenase (Acads) showed
      significant increased and decreased transcripts, respectively, consistent with
      their protein changes. These mRNAs were also studied in wild-type mice receiving
      squalene, where Mat1a was found increased and Acads decreased. However, this mRNA
      was significantly increased in the absence of apolipoprotein E. These results
      suggest that squalene action may be executed through a complex regulation of
      mitochondrial protein expression, including changes in Mat1a and Acads levels.
      Indeed, Mat1a is a target of squalene administration while Acads reflects the
      anti-steatotic properties of squalene.

PMID- 22402058
TI  - New insights into the brain protein metabolism of Gastrodia elata-treated rats by
      quantitative proteomics.
AB  - Gastrodia elata (tianma) is a traditional Chinese herbal medicine (TCM) often
      used for the treatment of cerebrovascular diseases. In this study, we
      investigated the effects of tianma on the brain protein metabolism by
      quantitative proteomics to gain evidence for a direct relationship between tianma
      treatment and brain functions. One-year-old rats were treated with tianma (~2.5
      g/kg/day) for 3months and the brain tissue proteome was analyzed by using the
      iTRAQ (isobaric tag for relative and absolute quantification) technology.
      According to our results, the long-term treatment with tianma could modulate the
      brain protein metabolism at the proteome level by down-regulating the expressions
      of various proteins, such as Gnao1 and Dctn2, which are related to neuronal
      growth cone control and synaptic activities. In addition, tianma treatment also
      induced the up-regulation of molecular chaperons and proteins related to the
      misfolded protein response, like Anxa5, and also other proteins involved in
      Huntington's disease (HD) (e.g. Pacsin1 and Arf3). Concluding, tianma could
      eventually contribute to activities related to synaptic plasticity and neuro
      restorative processes and thus might be a novel candidate agent for the treatment
      of neurodegenerative diseases by regulating the brain proteome.

PMID- 22402059
TI  - The effect of lipoic acid and vitamin E therapies in individuals with the
      metabolic syndrome.
AB  - The metabolic syndrome is associated with abnormal glucose and lipid metabolism,
      insulin resistance, increased oxidative stress and pro-inflammatory activity that
      increase the risk of type 2 diabetes and cardiovascular disease. The aim of this
      study was to investigate the effect of treatment with the antioxidant alpha
      lipoic acid (ALA) with or without vitamin E supplementation, on markers of
      insulin resistance and systemic inflammation and plasma nonesterified fatty acid
      (NEFA) concentrations in individuals with the metabolic syndrome. In a
      randomized, double-blind, placebo-controlled trial, subjects with the metabolic
      syndrome received ALA (600 mg/day, n = 34), vitamin E (100 IU/day, n = 36), both
      ALA and vitamin E (n = 41), or matching placebo (n = 40) for 1 year. Fasting
      circulating concentrations of glucose and insulin were measure every 3 months and
      NEFA, markers of inflammation, adiponectin and vitamin E were measured at 6
      monthly intervals. Plasma NEFA concentrations decreased [-10 (-18, 0)%] at a
      marginal level of significance (p = 0.05) in those who received ALA alone
      compared with placebo and decreased [-8 (-14, -1)% (95% CI)] significantly (P =
      0.02) in participants who were randomised to ALA with and without vitamin E
      compared with those who did not receive ALA. Fasting glucose, insulin,
      homeostatic model assessment of insulin resistance, adiponectin, and markers of
      inflammation did not change significantly during the study. These data suggest
      that prolonged treatment with ALA may modestly reduce plasma NEFA concentrations
      but does not alter insulin or glucose levels in individuals with the metabolic
      syndrome.

PMID- 22402060
TI  - Functional analysis of TCF7L2 genetic variants associated with type 2 diabetes.
AB  - BACKGROUND AND AIMS: Common non-coding variations within the TCF7L2 locus have a
      strong influence on type 2 diabetes (T2D) susceptibility through uncharacterised
      mechanisms. An islet-specific functional polymorphism has been identified,
      although this does not explain the association between genotype and gene
      expression in other cell types. This study sought to identify these other
      functional TCF7L2 variants. METHODS AND RESULTS: Alternative splicing and gene
      expression from TCF7L2 was examined from peripheral blood mononuclear cells from
      100 healthy Caucasians using two T2D-associated SNPs, rs7903146 and rs12255372.
      Electrophoretic mobility shift assays and luciferase reporter assays were
      performed with these SNPs and those in strong LD to determine potential SNP
      functionality. Individuals homozygous for rs7903146 and rs12255372 T2D risk
      alleles (TT/TT) expressed 2.6-fold greater levels of TCF7L2 mRNA compared to
      individuals homozygous for the non-risk alleles (CC/GG, p = 0.006), although
      differentially spliced TCF7L2 transcripts did not differ by T2D risk-associated
      genotype. From SNPs identified to be in strong LD with the T2D-associated SNPs,
      rs7903146 and rs12255372, five (rs4132670, rs4506565, rs7903146, rs7901695,
      rs17747324) demonstrated allele-specific binding in electrophoretic mobility
      shift assays (EMSA). In luciferase reporter assays, rs4132670 exhibited 1.3-fold
      higher levels of enhancer activity in the Huh7 cell line (p = 3.8 * 10(-5)) and 2
      fold higher levels in a WiDr colon carcinoma cell line (p = 0.008). CONCLUSIONS:
      These results suggest that rs4132670, located in a region of chromatin
      accessibility, is a non-tissue-specific candidate functional SNP that has the
      potential to play a role in TCF7L2 gene expression and T2D risk.

PMID- 22402062
TI  - Similar prediction of total mortality, diabetes incidence and cardiovascular
      events using relative- and absolute-component Mediterranean diet score: the SUN
      cohort.
AB  - BACKGROUND AND AIM: Accumulated evidence supports the effectiveness of
      Mediterranean-type diets (MeDiet) in reducing mortality and preventing several
      chronic diseases. Widely used scores to assess adherence to MeDiet are based on
      specific sample characteristics; alternatively, they might be built according to
      absolute/normative cut-off points for the consumption of specific food groups
      (pre-defined servings/day or/week). The aim of this study was to compare sample
      specific MeDiet adherence scores (MDS) versus absolute-normative scores
      (Mediterranean Diet Adherence Screener - MEDAS) on their association with
      macronutrient intake, total mortality and incidence of chronic diseases. DESIGN:
      SUN (Seguimiento Universidad de Navarra) dynamic prospective cohort study (60.5%
      women; mean age 38.4 years). METHODS AND RESULTS: In cross-sectional analyses
      (n=20,155) we evaluated macronutrient distribution according to MDS (based on 136
      item FFQ), MEDAS (based on 13 questions), and variants of both. In prospective
      analyses (n=9109; mean follow-up: 6.2 years), we evaluated disease incidence or
      mortality. Adherence to MeDiet increased with age and, as expected, was
      associated with higher fiber intake, lower total fat intake but higher
      monounsaturated/saturated fat ratio, using all scores. Among subjects initially
      free of cancer, diabetes, and cardiovascular disease (CVD), adherence to MeDiet
      appraised with an absolute-normative score (MEDAS) similarly predicted
      macronutrient distribution and disease incidence or mortality (diabetes
      incidence, CVD or all-cause mortality), when compared to a sample-specific score
      based on 136-item FFQ (MDS). CONCLUSIONS: Adherence to MeDiet was associated with
      a decreased incidence of a composite outcome including diabetes incidence,
      cardiovascular events incidence or all-cause mortality.

PMID- 22402061
TI  - Effects of exercise training on cardiac apoptosis in obese rats.
AB  - BACKGROUND AND AIM: The purpose of this study was to evaluate the effects of
      exercise training on cardiac apoptotic pathways in obesity. METHODS AND RESULTS:
      Sixteen lean Zucker rats (LZR) and sixteen obese Zucker rats (OZR) of 5-6 months
      of age as well as the other sixteen obese rats were subjected to treadmill
      running exercise for 1 h everyday for 3 months (OZR-EX). After exercise training
      or sedentary status of the rats, the excised hearts from the three groups were
      measured by heart weight index, H&E staining, TUNEL assays and Western blotting.
      Cardiac TUNEL-positive apoptotic cells, the protein levels of TNF alpha, Fas
      ligand, Fas receptors, Fas-associated death domain (FADD), Bad, Bax, activated
      caspase 8, activated caspase 9, and activated caspase 3 were higher in OZR than
      those in LZR. The protein levels of TNF alpha, Fas ligand, Fas receptors, FADD,
      activated caspase 8, and activated caspase 3 (Fas pathway) and the protein levels
      of Bad, Bax, Bax-to-Bcl2 ratio, activated caspase 9, and activated caspase 3
      (mitochondria pathway) were lower in OZR-EX than those in OZR. CONCLUSION:
      Cardiac Fas-dependent and mitochondria-dependent apoptotic pathways become more
      activated in obesity. Exercise training can prevent obesity-activated cardiac Fas
      dependent and mitochondria-dependent apoptotic pathways. Our findings demonstrate
      a new therapeutic effect of exercise training to prevent delirious cardiac Fas
      mediated and mitochondria-mediated apoptosis in obesity.

PMID- 22402063
TI  - Renin as a biomarker of cardiovascular disease in clinical practice.
AB  - The search for novel circulating blood biomarkers as predictors of cardiovascular
      (CV) risk and prognosis is a continuing field of interest in clinical medicine.
      Biomarkers from several pathophysiological pathways, including markers of organ
      damage, of inflammation, of the atherosclerotic process and of the coagulation
      pathway, have been investigated in the last decades. A particular interest has
      been raised for neurohormonal factors. The role of the activation of the
      sympathetic system and the renin-angiotensin-aldosterone system (RAAS) in the
      development of CV diseases has been extensively explored. Renin is the first
      limiting step of the RAAS and its role as a biomarker to improve CV risk
      stratification still remains a topic of debate. Several studies have shown that
      elevated plasma renin activity is associated with increased morbidity and
      mortality in patients with CV disease. The aim of this paper is to critically
      evaluate the evidence on the role of renin as a biomarker of CV risk and
      prognosis. With the new advances of pharmacological treatment acting on the RAAS,
      the effect of elevated levels of renin on the prognosis of these patients becomes
      even more intriguing.

PMID- 22402064
TI  - The ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) K121Q polymorphism
      modulates the beneficial effect of weight loss on fasting glucose in non-diabetic
      individuals.
AB  - BACKGROUND AND AIMS: Several studies have reported that the ectonucleotide
      pyrophosphatase phosphodiesterase 1 (ENPP1) K121Q polymorphism (rs1044498)
      interacts with increased adiposity in affecting glucose homeostasis and insulin
      sensitivity. Conversely, one would expect that the amelioration of glucose
      homeostasis observed after weight loss is modulated by the ENPP1 K121Q
      polymorphism. The aim of our study was to test such hypothesis, in non-diabetic
      overweight-obese individuals. METHODS AND RESULTS: Two hundred eleven non
      diabetic overweight-obese individuals were studied. Body mass index (BMI),
      fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR
      index) and lipid levels were obtained before and after 6-week lifestyle
      intervention (LI; diet and exercise) and their changes calculated as baseline
      minus 6-week values. LI decreased BMI, glucose, HOMA-IR and triglyceride levels
      (p < 0.001 for all). No difference across genotype groups (160 KK and 51 KQ or QQ
      - named as XQ - individuals) was observed in these changes. In a multivariate
      model, BMI changes predicted fasting glucose changes (beta = 0.139 mmol/L (2.50
      mg/dl) for 1 unit BMI change, p = 0.005). This correlation was not significant
      among KK individuals (beta = 0.082; p = 0.15), while much steeper and highly
      significant among XQ individuals (beta = 0.336; p = 0.00008) (p-value for Q121-by
      weight loss interaction = 0.047). CONCLUSION: Individuals carrying the ENPP1 Q121
      variant are highly responsive to the effect of weight loss on fasting glucose.
      This reinforces the previously suggested hypothesis that the Q121 variant
      interacts with adiposity in modulating glucose homeostasis.

PMID- 22402066
TI  - Spatio-temporal mapping of motor preparation for self-paced saccades.
AB  - We investigated the movement related cortical potentials (MRCPs) associated with
      self-paced horizontal voluntary saccades and evaluated their cortical sources by
      applying dipole model. A fixation point and two targets (6 degrees  of
      eccentricity in the left and right fields) were continuously displayed on a
      screen. A first group (15 subjects) performed a saccade toward one of the lateral
      targets immediately followed by a re-centering saccade. A second group (15
      subjects) performed a saccade followed by a long fixation (few seconds) before a
      re-centering. Results showed a sequence of activities in contralateral Intra
      Parietal Sulcus (IPS), Supplementary Eye Fields and Frontal Eye Fields. In the
      case of long-fixation-saccades, an additional source in ipsilateral IPS was
      detected in the planning phase. The amplitude and timing of the planning phase,
      associated with BP components, were influenced by task demands. Similarity and
      difference between MRCPs for eyes and limbs movements are also presented.

PMID- 22402065
TI  - Does moderate drinking harm the fetal brain? Insights from animal models.
AB  - Although public health campaigns advise pregnant women to abstain from ethanol,
      drinking during pregnancy is pervasive. Here, we highlight recent studies that
      have clearly demonstrated long-lasting neurobehavioral deficits in the offspring
      of laboratory animals exposed to moderate levels of ethanol during development.
      Alterations in learning, memory, motor coordination, social behavior, and stress
      responses were identified in these animals. Increased vulnerability to substance
      abuse was also demonstrated. These behavioral alterations have been associated
      with impairments in neurotransmitter systems, neuromodulators, and/or synaptic
      plasticity in several brain regions. With this review we hope to contribute to a
      better appreciation of the potential effects of developmental exposure to
      moderate ethanol levels, leading to better interventions aimed at relieving fetal
      alcohol spectrum disorders.

PMID- 22402067
TI  - An update on cardioprotection: a review of the latest adjunctive therapies to
      limit myocardial infarction size in clinical trials.
AB  - Acute myocardial infarction (AMI) with subsequent left ventricular dysfunction
      and heart failure continues to be a major cause of morbidity and mortality in the
      Western world. Rapid advances in the treatment of AMI, mainly through timely
      reperfusion, have substantially improved outcomes in patients presenting with
      acute coronary syndrome and particularly ST-segment elevation myocardial
      infarction. A vast amount of research, both translational and clinical, has been
      published on various pharmacological and interventional techniques to prevent
      myocardial cell death during the time of ischemia and subsequent reperfusion.
      Several methods of cardioprotection have shown the ability to limit myocardial
      infarction size in clinical trials. Examples of interventional techniques that
      have proven beneficial are ischemic post-conditioning and remote ischemic per
      conditioning, both of which can reduce infarction size. Lowering core body
      temperature with cold saline infusion and cooling catheters have also been shown
      to be effective in certain circumstances. The most promising pharmaceutical
      cardioprotective agents at this time appear to be adenosine, atrial natriuretic
      peptide, and cyclosporine, with other potentially effective medications in the
      pipeline. Additional pre-clinical and clinical research is needed to further
      investigate newer cardioprotective strategies to continue the current trend of
      improving outcomes following AMI.

PMID- 22402068
TI  - Dietary intervention prevents dyslipidemia associated with highly active
      antiretroviral therapy in human immunodeficiency virus type 1-infected
      individuals: a randomized trial.
AB  - OBJECTIVES: The purpose of this study was to evaluate the efficacy of dietary
      intervention on blood lipids of human immunodeficiency virus (HIV)-1-infected
      patients who are started on highly active antiretroviral therapy (HAART).
      BACKGROUND: Current guidelines recommend diet as first-step intervention for HIV
      1-infected individuals with HAART-related dyslipidemia, but there is no evidence
      from randomized trials to support this recommendation. METHODS: Eighty-three HIV
      1-infected patients, naive from HAART, were randomly assigned to HAART with
      dietary intervention (diet group, n = 43) or HAART without dietary intervention
      (control group, n = 40) for 12 months. Diet, according to the National
      Cholesterol Education Program, was given every 3 months. Before and after
      intervention, 24-h food records and lipid profile were obtained. Data were
      analyzed by intention to treat, using mixed-effects models. RESULTS: Diet
      resulted in reduction of percentage of fat intake (from 31 +/- 7% to 21 +/- 3% of
      calories), while controls presented no change in percentage of fat intake. Plasma
      cholesterol (from 151 +/- 29 mg/dl to 190 +/- 33 mg/dl) and low-density
      lipoprotein cholesterol (from 85 +/- 24 mg/dl to 106 +/- 31 mg/dl) increased in
      the control group and were unchanged in the diet group. Plasma triglycerides were
      reduced by diet (from 135 +/- 67 mg/dl to 101 +/- 42 mg/dl) and increased in the
      control group (from 134 +/- 70 mg/dl to 160 +/- 76 mg/dl). After 1-year follow
      up, 21% of patients who received diet had lipid profile compatible with
      dyslipidemia compared with 68% (p < 0.001) of controls. CONCLUSIONS: Among HIV-1
      positive individuals naive of previous treatment, diet prevents dyslipidemia
      associated with HAART. (Effect of Nutritional Intervention on the Lipid Profile
      of HIV-Positive Patients Who Start HAART: a Randomized Trial; NCT00429845).

PMID- 22402069
TI  - Nutritional therapy to prevent dyslipidemia in patients starting antiretroviral
      therapy for human immunodeficiency virus.

PMID- 22402070
TI  - Current perspectives on coronary chronic total occlusions: the Canadian
      Multicenter Chronic Total Occlusions Registry.
AB  - OBJECTIVES: The purpose of this study was to determine the prevalence, clinical
      characteristics, and management of coronary chronic total occlusions (CTOs) in
      current practice. BACKGROUND: There is little evidence in contemporary literature
      concerning the prevalence, clinical characteristics, and treatment decisions
      regarding patients who have coronary CTOs identified during coronary angiography.
      METHODS: Consecutive patients undergoing nonurgent coronary angiography with CTO
      were prospectively identified at 3 Canadian sites from April 2008 to July 2009.
      Patients with previous coronary artery bypass graft surgery or presenting with
      acute ST-segment elevation myocardial infarction were excluded. Detailed baseline
      clinical, angiographic, electrocardiographic, and revascularization data were
      collected. RESULTS: Chronic total occlusions were identified in 1,697 (18.4%)
      patients with significant coronary artery disease (>50% stenosis in >=1 coronary
      artery) who were undergoing nonemergent angiography. Previous history of
      myocardial infarction was documented in 40% of study patients, with
      electrocardiographic evidence of Q waves corresponding to the CTO artery
      territory in only 26% of cases. Left ventricular function was normal in >50% of
      patients with CTO. Half the CTOs were located in the right coronary artery.
      Almost half the patients with CTO were treated medically, and 25% underwent
      coronary artery bypass graft surgery (CTO bypassed in 88%). Percutaneous coronary
      intervention was done in 30% of patients, although CTO lesions were attempted in
      only 10% (with 70% success rate). CONCLUSIONS: Chronic total occlusions are
      common in contemporary catheterization laboratory practice. Prospective studies
      are needed to ascertain the benefits of treatment strategies of these complex
      patients.

PMID- 22402071
TI  - Impact of noncardiac comorbidities on morbidity and mortality in a predominantly
      male population with heart failure and preserved versus reduced ejection
      fraction.
AB  - OBJECTIVES: The aim of this study was to evaluate the prevalence and prognostic
      impacts of noncardiac comorbidities in patients with heart failure (HF) with
      preserved ejection fraction (HFpEF) compared with those with HF with reduced
      ejection fraction (HFrEF). BACKGROUND: There is a paucity of information on the
      comparative prognostic significance of comorbidities between patients with HFpEF
      and those with HFrEF. METHODS: In a national ambulatory cohort of veterans with
      HF, the comorbidity burden of 15 noncardiac comorbidities and the impacts of
      these comorbidities on hospitalization and mortality were compared between
      patients with HFpEF and those with HFrEF. RESULTS: The cohort consisted of 2,843
      patients with HFpEF and 6,599 with HFrEF with 2-year follow-up. Compared with
      patients with HFrEF, those with HFpEF were older and had higher prevalence of
      chronic obstructive pulmonary disease, diabetes, hypertension, psychiatric
      disorders, anemia, obesity, peptic ulcer disease, and cancer but a lower
      prevalence of chronic kidney disease. Patients with HFpEF had lower HF
      hospitalization, higher non-HF hospitalization, and similar overall
      hospitalization compared with those with HFrEF (p < 0.001, p < 0.001, and p =
      0.19, respectively). An Increasing number of noncardiac comorbidities was
      associated with a higher risk for all-cause admissions (p < 0.001). Comorbidities
      had similar impacts on mortality in patients with HFpEF compared with those with
      HFrEF, except for chronic obstructive pulmonary disease, which was associated
      with a higher hazard (1.62 [95% confidence interval: 1.36 to 1.92] vs. 1.23 [95%
      confidence interval: 1.11 to 1.37], respectively, p = 0.01 for interaction) in
      patients with HFpEF. CONCLUSIONS: There is a higher noncardiac comorbidity burden
      associated with higher non-HF hospitalizations in patients with HFpEF compared
      with those with HFrEF. However, individually, most comorbidities have similar
      impacts on mortality in both groups. Aggressive management of comorbidities may
      have an overall greater prognostic impact in HFpEF compared to HFrEF.

PMID- 22402072
TI  - Outcomes in patients with heart failure with preserved ejection fraction: it is
      more than the heart.

PMID- 22402073
TI  - Cardiac fibrosis in human transplanted hearts is mainly driven by cells of
      intracardiac origin.
AB  - OBJECTIVES: The aim of our study was to determine the origin of collagen in the
      progression of myocardial fibrosis in human adult transplanted hearts.
      BACKGROUND: Changes in the cardiac interstitial collagen network are thought to
      contribute to abnormal stiffness and function of the myocardium. The origin of
      fibrosis-mediating fibroblasts remains incompletely understood, and conflicting
      data from animal models suggest that they are either derived intracardially or
      immigrate from extracardiac sources. METHODS: We studied endomyocardial biopsy
      specimens from 7 sex-mismatched (female donor heart to a male recipient) heart
      transplant recipients by a combination of chromogen in situ hybridization using
      probes specific for Y chromosomes with immunohistochemistry. On the basis of
      differences in genetic polymorphisms in the type III collagen gene between donor
      and recipient tissue, we quantitatively determined origin-specific type III
      collagen gene expression in fibrotic areas containing fibroblasts of putative
      extracardiac origin. RESULTS: In areas of increased cardiac fibrosis years after
      heart transplantation, a substantial number of Y chromosome-positive spindle
      shaped cells with a fibroblast-like appearance were detected. Many of these cells
      were identified as macrophages, and measurement of origin-specific type III
      collagen synthesis identified cells of intracardiac origin as the main source for
      collagen turnover in human cardiac fibrosis. CONCLUSIONS: Our data suggest that,
      in human myocardium, cardiac fibrosis due to chronic allograft rejection up to 15
      years after transplantation or scar formation provoked by mechanical trauma is
      mainly driven by fibroblasts of intracardiac origin. Antifibrotic treatment
      strategies, therefore, should target molecular mechanisms that induce
      fibrillogenesis of cells with intracardiac origin.

PMID- 22402075
TI  - Repolarization recipes for atrial fibrillation: beyond single channel variants.

PMID- 22402074
TI  - Epistatic effects of potassium channel variation on cardiac repolarization and
      atrial fibrillation risk.
AB  - OBJECTIVES: The aim of this study was to evaluate the role of cardiac K(+)
      channel gene variants in families with atrial fibrillation (AF). BACKGROUND: The
      K(+) channels play a major role in atrial repolarization but single mutations in
      cardiac K(+) channel genes are infrequently present in AF families. The
      collective effect of background K(+) channel variants of varying prevalence and
      effect size on the atrial substrate for AF is largely unexplored. METHODS: Genes
      encoding the major cardiac K(+) channels were resequenced in 80 AF probands.
      Nonsynonymous coding sequence variants identified in AF probands were evaluated
      in 240 control subjects. Novel variants were characterized using patch-clamp
      techniques and in silico modeling was performed using the Courtemanche atrial
      cell model. RESULTS: Nineteen nonsynonymous variants in 9 genes were found,
      including 11 rare variants. Rare variants were more frequent in AF probands
      (18.8% vs. 4.2%, p < 0.001), and the mean number of variants was greater (0.21
      vs. 0.04, p < 0.001). The majority of K(+) channel variants individually had
      modest functional effects. Modeling simulations to evaluate combinations of K(+)
      channel variants of varying population frequency indicated that simultaneous
      small perturbations of multiple current densities had nonlinear interactions and
      could result in substantial (>30 ms) shortening or lengthening of action
      potential duration as well as increased dispersion of repolarization.
      CONCLUSIONS: Families with AF show an excess of rare functional K(+) channel gene
      variants of varying phenotypic effect size that may contribute to an atrial
      arrhythmogenic substrate. Atrial cell modeling is a useful tool to assess
      epistatic interactions between multiple variants.

PMID- 22402076
TI  - The athlete's heart in adolescent Africans: an electrocardiographic and
      echocardiographic study.
AB  - OBJECTIVES: The goal of this study was to define electrocardiographic (ECG) and
      echocardiographic characteristics of adolescent African athletes. BACKGROUND:
      Recent observations in African athletes reported large prevalence of left
      ventricular (LV) hypertrophy and ECG abnormalities. No data, so far, exist for
      adolescent Africans, which comprise a growing proportion of
      competitive/professional athletes. METHODS: The study included 154 soccer players
      participating at the 8th African Under-17 Championship of 2009, representing
      Algeria, Burkina Faso, Cameroon, Gambia, Guinea, Malawi, Nigeria, and Zimbabwe.
      For comparison, 62 Italian players with similar ages, sport achievements, and
      training schedules were included. RESULTS: African athletes showed higher R5/S1
      wave voltages than Caucasian athletes (48.6 +/- 12.1 mm vs. 34.1 +/- 8.9 mm; p <
      0.01), larger prevalence of ECG LV hypertrophy (89% vs. 42%; p < 0.001), ST
      segment elevation (91% vs. 56%; p < 0.001), and deeply inverted, or diffusely
      flat/biphasic, T waves (14% vs. 3% [p < 0.05] and 25% vs. 8% [p < 0.008],
      respectively). LV wall thicknesses were increased in Africans by 5% compared with
      Caucasians, and exceeded normal limits (>=13 mm) in 4 Africans but in no
      Caucasians. No athlete showed evidence of cardiomyopathies (i.e., hypertrophic
      cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy). On individual
      analysis, Algerians showed lower R/S-wave voltages compared with other African
      athletes. Increased wall thickness (>=13 mm) was observed only in sub-Saharian
      athletes (from Burkina Faso, Cameroon, and Niger). CONCLUSIONS: African athletes
      displayed large proportion of ECG abnormalities, including a striking increase in
      R/S-wave voltage, ST-segment elevation, and deeply inverted or diffusely flat T
      waves by adolescence. LV remodeling in African athletes was characterized by a
      disproportionate wall thickening than in Caucasians but similar cavity size.
      Finally, distinctive peculiarities existed in African athletes according to the
      country (and ethnic) origin.

PMID- 22402077
TI  - Hemopericardium, shock, and a linear density in the ascending aorta: is it a
      dissection?

PMID- 22402078
TI  - "Framing" the vessel: the critical importance of volumetric analysis during
      serial intravascular imaging studies.

PMID- 22402080
TI  - Antiarrhythmic drug therapy in 2012: time to finally open our eyes!

PMID- 22402082
TI  - Subacute tuberculous constrictive pericarditis.

PMID- 22402083
TI  - Prospective study of gefitinib readministration after chemotherapy in patients
      with advanced non-small-cell lung cancer who previously responded to gefitinib.
AB  - INTRODUCTION: Salvage treatment for acquired resistance to epidermal growth
      factor receptor tyrosine kinase inhibitor in patients with non-small-cell lung
      cancer is a matter of clinical concern. Several retrospective reports have
      indicated the usefulness of epidermal growth factor receptor tyrosine kinase
      inhibitor readministration; however, there have been few prospective studies.
      MATERIALS AND METHODS: This study was designed to prospectively evaluate the
      clinical efficacy of gefitinib readministration in patients with advanced or
      metastatic non-small-cell lung cancer who responded well to initial gefitinib
      treatment. The subjects received at least 1 regimen of cytotoxic chemotherapy
      after progressive disease with the initial gefitinib therapy. Gefitinib
      administration (250 mg/d, orally) was started after progressive disease with the
      previous chemotherapeutic regimen. The primary endpoint in the present study was
      the response rate. RESULTS: Twenty patients were enrolled between April 2007 and
      May 2011. Three patients achieved partial response, and 6 showed stable disease.
      Thus, the overall response rate and disease control rate of gefitinib
      readministration were 15% (95% CI, 3.21-37.9) and 45% (95% CI, 23.1-68.5),
      respectively. Median progression-free survival and overall survival from the
      start of gefitinib readministration were 2.0 months (95% CI, 0.9-3.1 months) and
      12.0 months (95% CI, 8.0-16.0 months), respectively. CONCLUSION: These results
      suggest that gefitinib readministration may be an option, albeit with a low
      response rate and short progression-free survival, for patients who responded
      well to initial gefitinib followed by systemic chemotherapy. These findings
      provide valuable information for the management of previous gefitinib responders.

PMID- 22402084
TI  - Moving toward mainstream: perspectives on enhancing therapy with men.
AB  - Psychotherapists began sharing their clinical experiences with men's gender
      related psychological issues and the challenges of addressing them in therapy
      during the late 1970s and early 1980s (e.g., O'Neil, 1981; Scher, 1979; Skovholt,
      1978). However, it has taken several decades for these messages and the
      accompanying research to yield advances that are being adopted into more
      mainstream psychotherapeutic practices. Over the recent three decades, the
      theory, research, and clinical wisdom about psychotherapy with men can be viewed
      as falling into several main clusters. Specifically, there is literature and
      research providing: - General information on masculine socialization and the
      psychology of men. - Information about specific issues that men and male clients
      bring to therapy. - Information about the expectations and experiences of
      specific groups of men (e.g., men of differing racial/ethnic backgrounds,
      geographical regions, age cohorts, spiritual/religious beliefs, differing
      physical ability statuses). - Suggestions for addressing men's reluctance to seek
      psychotherapy and the challenges associated with forming therapeutic working
      alliances with men when they do come to therapy. - Suggestions regarding
      adjustments to psychotherapeutic processes for conducting effective psychotherapy
      with men. - Development and assessment of instruments to assess endorsement of
      various male norms and of aspects of men's gender role conflict and stress.
      Reviewing the earliest writings, some of these pioneering therapists' initial
      clinical observations remain highly relevant today.

PMID- 22402085
TI  - Identifying, affirming, and building upon male strengths: the positive
      psychology/positive masculinity model of psychotherapy with boys and men.
AB  - The bulk of the extant literature on the psychology of boys, men and masculinity
      has been focused on the important challenges of: a) creating an awareness about
      the detrimental effects of constricted forms of masculinity on boys and men and
      their relationships with others; and b) developing remedial approaches to
      psychotherapy that are designed to help boys and men recover from dysfunctional
      masculinity. The purpose of this article is to expand this literature by
      introducing the positive psychology/positive masculinity (PPPM) framework, which
      emphasizes male strengths as the starting point for psychotherapy with boys and
      men. The central principles of the PPPM framework are described, and the
      application of the PPPM model with an adult man in psychotherapy is presented.
      The implications of the PPPM model for future practice and research pertaining to
      boys, men, and masculinity are discussed.

PMID- 22402086
TI  - Helping men with the trauma of miscarriage.
AB  - Although much has been written about women and miscarriage, little has been
      researched or written about the partners of these women and their reactions to
      the pregnancy loss. The purpose of this paper is to review what is known about
      the subject and to suggest an approach to psychotherapy that is sensitive to the
      needs of these men and helps them make sense of their loss.

PMID- 22402056
TI  - Rivaroxaban compared with warfarin in patients with atrial fibrillation and
      previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF.
AB  - BACKGROUND: In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin
      in preventing stroke or systemic embolism among patients with atrial fibrillation
      (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban
      compared with warfarin is consistent among the subgroups of patients with and
      without previous stroke or transient ischaemic attack (TIA). METHODS: In ROCKET
      AF, patients with AF who were at increased risk of stroke were randomly assigned
      (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose
      warfarin (international normalised ratio 2.0-3.0). Patients and investigators
      were masked to treatment allocation. Between Dec 18, 2006, and June 17, 2009, 14
      264 patients from 1178 centres in 45 countries were randomly assigned. The
      primary endpoint was the composite of stroke or non-CNS systemic embolism. In
      this substudy we assessed the interaction of the treatment effects of rivaroxaban
      and warfarin among patients with and without previous stroke or TIA. Efficacy
      analyses were by intention to treat and safety analyses were done in the on
      treatment population. ROCKET AF is registered with ClinicalTrials.gov, number
      NCT00403767. FINDINGS: 7468 (52%) patients had a previous stroke (n=4907) or TIA
      (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per
      100 person-years for the primary endpoint in patients treated with rivaroxaban
      compared with warfarin was consistent among patients with previous stroke or TIA
      (2.79% rivaroxaban vs 2.96% warfarin; hazard ratio [HR] 0.94, 95% CI 0.77-1.16)
      and those without (1.44%vs 1.88%; 0.77, 0.58-1.01; interaction p=0.23). The
      number of major and non-major clinically relevant bleeding events per 100 person
      years in patients treated with rivaroxaban compared with warfarin was consistent
      among patients with previous stroke or TIA (13.31% rivaroxaban vs 13.87%
      warfarin; HR 0.96, 95% CI 0.87-1.07) and those without (16.69%vs 15.19%; 1.10,
      0.99-1.21; interaction p=0.08). INTERPRETATION: There was no evidence that the
      relative efficacy and safety of rivaroxaban compared with warfarin was different
      between patients who had a previous stroke or TIA and those who had no previous
      stroke or TIA. These results support the use of rivaroxaban as an alternative to
      warfarin for prevention of recurrent as well as initial stroke in patients with
      AF. FUNDING: Johnson and Johnson Pharmaceutical Research and Development and
      Bayer HealthCare.

PMID- 22402087
TI  - Not supposed to feel this: traditional masculinity in psychotherapy with male
      veterans returning from Afghanistan and Iraq.
AB  - Traditional masculine socialization presents challenges in psychotherapy, for
      example, by decreasing the likelihood of help-seeking and by making emotion-laden
      content more difficult to address. While this has been established in civilian
      populations, more intense forms of masculine socialization found in military
      settings may amplify such issues in male veteran populations. Male veterans
      returning from and Afghanistan (OEF) and Iraq (OIF) exhibit strong traditional
      masculine socialization and generally present in a unique manner. It is posited
      that OEF/OIF male veterans' unique presentation is in large part because of an
      interaction between high degrees of endorsement of traditional masculine gender
      role norms, relative youth, recency of distressing events, and recent experience
      in the social context of the military where traditional masculinity is
      reinforced. The impact of these variables on the psychotherapeutic process for
      male OEF/OIF veterans is significant and likely adds to ambivalence about change
      and increases dropout from psychotherapy. Modifications of traditional
      psychotherapeutic approaches designed to address traditional masculine gender
      role norms and their many interactions with other variables are discussed.

PMID- 22402088
TI  - To accept a pilot? Addressing men's ambivalence and altering their expectancies
      about therapy.
AB  - When considering the challenges therapists encounter with their male clients,
      perhaps the most daunting tasks occur at the very beginning. Getting boys and men
      to avail themselves of psychological services is the first challenge. But when
      men do present, the second challenge is to get them to trust therapists
      sufficiently enough to share their issues and to form an effective working
      alliance. This article describes these gender-related challenges from male
      clients' point of view, and then elaborates upon effective techniques to help
      them engage in and benefit from psychotherapy. We suggest that good therapists
      for men, like good ship pilots, are informed and prepared. They learn the major
      cognitive and emotional issues they are likely to encounter with their male
      clients, and develop a variety of ways to help their male clients navigate the
      tricky psychological issues of their lives.

PMID- 22402089
TI  - "Gender aware therapy" for professional men in a day treatment center.
AB  - High accountability men in the medical, legal, corporate, and mental health
      professions sometimes engage in behavior that violates their fiduciary
      responsibilities. These highly skilled men may engage in disruptive or explosive
      behavior, cross sexual boundaries with clients or patients, abuse substances, or
      have other psychiatric problems that compromise their workplace performance. When
      this occurs, licensing boards, professional societies, or supervising executives
      often require the dysregulated man to seek assistance. This article reports on
      ways the Professional Renewal Center incorporates recommendations from "Gender
      Aware Therapy" in developing a male-friendly approach to conducting comprehensive
      multidisciplinary psychological assessments, and to providing intensive,
      multimodal, weeks-long treatment services.

PMID- 22402090
TI  - Helpful and hindering events in psychotherapy: a practice research network study.
AB  - This paper presents the findings of a psychotherapy process study conducted
      within the Pennsylvania Psychological Association Practice Research Network (PPA
      PRN). The investigation was the product of a long-term collaborative effort, both
      in terms of the study design and implementation, between experienced clinicians
      of various theoretical orientations and full-time psychotherapy researchers.
      Based on a relatively large sample of clients seen in independent practice
      settings, close to 1,500 therapeutic events (described by clients and therapists
      as being particularly helpful or hindering) were collected. These events were
      coded by three independent observers using a therapy content analysis system.
      Among the findings, both clients and therapists perceived the fostering of self
      awareness as being particularly helpful. The results also point to the importance
      of paying careful attention to the therapeutic alliance and other significant
      interpersonal relationships. The merits and difficulties of conducting
      scientifically rigorous and clinically relevant studies in naturalistic contexts
      are also discussed.

PMID- 22402091
TI  - Psychotherapists, researchers, or both? A qualitative analysis of
      psychotherapists' experiences in a practice research network.
AB  - This paper describes the experiences of psychotherapists who, as part of a
      practice research network (PRN), collaborated with researchers in designing and
      conducting a psychotherapy study within their own clinical practices. A
      qualitative analysis of interviews conducted with these psychotherapists led to
      the delineation of several benefits (e.g., learning information that improved
      their work with clients and feeling that they were contributing to research that
      would be useful for psychotherapists) and difficulties for them and their clients
      (e.g., time and effort required to integrate research protocol into routine
      clinical practice) that psychotherapists associated with their participation in
      the PRN. Also identified were a number of strategies used by psychotherapists to
      address obstacles that they encountered, as well as general recommendations for
      future PRN studies. As a whole, the experiences of these psychotherapists are
      likely to provide valuable lessons for the survival and growth of what is viewed
      by many as a promising pathway for building a stronger bridge between practice
      and research.

PMID- 22402092
TI  - Session and intersession experience related to treatment outcome in bulimia
      nervosa.
AB  - Treatment in bulimia nervosa is challenging, with rates of successful treatments
      for only about 50% of all patients. This study aimed to identify predictors of
      outcome through secondary analysis of data from a randomized clinical trial that
      compared inpatient and day hospital treatment for bulimia. Process measures
      included assessments of patients' in-session experiences, therapeutic alliance,
      and therapy-related intersession experiences (ISE). ISE measures were better
      predictors of outcome than pretreatment variables (e.g., social adjustment) or
      global therapeutic alliance. Outcome at 3 month follow-up was strongly related to
      the ISE dimension Recreating Therapeutic Dialogue with Negative Emotions,
      indicating a heightened risk of failure. Prediction of outcome by these variables
      showed a sensitivity of 0.86 and a specificity of 0.78, and 83% of patients could
      be correctly classified. These results show that certain aspects of ISE may serve
      as early and reliable indicators of long term treatment failure, prompting
      alternate treatment approaches and opening new directions of research.

PMID- 22402093
TI  - Intersecting losses: working with the inevitable vicissitudes in therapist and
      client lives.
AB  - Therapists working with clients with severe trauma histories over long periods of
      time may find themselves managing traumatic events in their own lives-illness,
      divorce, death-at the same time as they are assisting their clients to live
      productively with their painful pasts. While a few accounts exist describing how
      therapists deal with single overwhelming events, very little has been written
      about how therapists manage ongoing or prolonged episodes of severe stressors
      with a busy clinical practice of clients with severe trauma histories. Yet, we
      know that support for therapists is crucial to longevity in the field and we also
      know that learning from the experience of others is a highly recommended form of
      support. This paper is an account by a senior clinician of how she has maintained
      a productive clinical practice despite personal losses. Therapists who struggle
      with personal losses probably deal with choices related to self-disclosure more
      than therapists who do not have such experiences; they have repeated
      opportunities to establish appropriate and effective levels of self-disclosure
      for them and the people with whom they work. The paper presents a template for
      thinking about the risks and benefits of self-disclosure while at the same time
      modeling a level of self-disclosure that may be beneficial to therapists looking
      for examples.

PMID- 22402094
TI  - Rapid treatment of PTSD: why psychological exposure with acupoint tapping may be
      effective.
AB  - Combining brief psychological exposure with the manual stimulation of acupuncture
      points (acupoints) in the treatment of posttraumatic stress disorder (PTSD) and
      other emotional conditions is an intervention strategy that integrates
      established clinical principles with methods derived from healing traditions of
      Eastern cultures. Two randomized controlled trials and six outcome studies using
      standardized pre- and posttreatment measures with military veterans, disaster
      survivors, and other traumatized individuals corroborate anecdotal reports and
      systematic clinical observation in suggesting that (a) tapping on selected
      acupoints, (b) during imaginal exposure, (c) quickly and permanently reduces
      maladaptive fear responses to traumatic memories and related cues. The approach
      has been controversial. This is in part because the mechanisms by which
      stimulating acupoints can contribute to the treatment of serious or longstanding
      psychological disorders have not been established. Speculating on such
      mechanisms, the current paper suggests that adding acupoint stimulation to brief
      psychological exposure is unusually effective in its speed and power because
      deactivating signals are sent directly to the amygdala, resulting in the rapid
      attenuation of threat responses to innocuous stimuli. This formulation and the
      preliminary evidence supporting it could, if confirmed, lead to more powerful
      exposure protocols for treating PTSD.

PMID- 22402095
TI  - Psychological and psychosocial aspects of the solid organ transplant experience-
      a practice review.
AB  - There is an increasing need for empirically based psychotherapy interventions for
      individuals and their caregiving systems undergoing the solid organ transplant
      process. Research suggests that the organ transplant recipient experiences an
      improvement in physical and social functioning and return to daily activities,
      but not consistently positive change in psychological health. The transplantation
      process leaves the recipient with a mixture of distressing and challenging
      experiences. Three temporal stages have been identified in the process: the
      pretransplant stage, preoperative/candidacy waiting period, and the
      posttransplant stage, each holding psychological and social issues. The construct
      of quality-of-life, identified by critical factors and benchmarks in the
      therapeutic process for transplant recipients, is defined differently in the
      medical and psychological literature. Differences are discussed in terms of
      therapeutic interventions. Caregivers are found to experience their own
      challenges when an intimate has a solid organ transplant. Therapeutic
      interventions for the caregiving system include stress management,
      psychoeducation, and repair of relational ruptures.

PMID- 22402096
TI  - Psychotherapy appointment no-shows: rates and reasons.
AB  - Patients who frequently miss or do not show for their scheduled psychotherapy
      appointments create administrative and clinical difficulties, and may not be
      receiving effective treatment. Prior research has predominately focused on either
      identifying demographic and administrative factors related to patient no-show
      rates or evaluating the effectiveness of administrative procedures for reducing
      no-shows. This paper attempts to identify rates of missed appointments in
      clinical practice and explore more specific clinical process factors related to
      patient no-shows. Psychotherapists (N = 24) and their patients (N = 542) in the
      outpatient department of a public safety-net hospital were surveyed to examine
      how frequently patients missed scheduled psychotherapy appointments and for what
      reasons. Findings indicate that the majority of missed appointments were
      accounted for by patients with occasional absences (approx. 1 per month), while
      only a small percentage of patients missed appointments with high frequency.
      Patients missed their psychotherapy appointments for a number of reasons,
      including clinical symptoms, practical matters, motivational concerns, and
      negative treatment reactions.

PMID- 22402097
TI  - Patient interpersonal impacts and the early therapeutic alliance in interpersonal
      therapy for depression.
AB  - The therapeutic alliance consistently predicts positive psychotherapy outcomes.
      Thus, it is important to uncover factors that relate to alliance development. The
      goal of this study was to examine the association between patient interpersonal
      characteristics and alliance quality in interpersonal therapy for depression.
      Data derive from a subsample (n = 74) of a larger naturalistic database of
      outpatients treated at a mood disorders clinic of a university-affiliated
      psychiatric hospital. Following Session 3 of treatment, therapists completed the
      Impact Message Inventory (Kiesler & Schmidt, 1993) to assess patients'
      interpersonal impacts on them. Also following Session 3, patients completed the
      Working Alliance Inventory (Horvath & Greenberg, 1989) to assess alliance
      quality. As predicted, patients' affiliative interpersonal impacts, as perceived
      by their therapists, were positively associated with alliance quality,
      controlling for baseline depression severity. Although unrelated to the initial
      hypotheses, patients concurrently taking psychotropic medications reported better
      alliances than patients receiving psychotherapy only.

PMID- 22402100
TI  - New sucrose esters from the fruits of Physalis solanaceus.
AB  - Three new sucrose esters (1-3) along with several known compounds were isolated
      from the fruits of Physalis solanaceus. The structural elucidation of the
      isolates was based on their spectroscopic characteristics mainly those of MS and
      NMR.

PMID- 22402099
TI  - Comparative study on antioxidative and macrophage-stimulating activities of
      polyguluronic acid (PG) and polymannuronic acid (PM) prepared from alginate.
AB  - The antioxidant and macrophage-stimulating activities of polyguluronic acid (PG)
      and polymannuronic acid (PM) prepared from alginate were examined. A
      chemiluminescence (CL) method using a luminol analog, L-012, showed that both PM
      and PG scavenge superoxide produced by hypoxanthine-xanthine oxidase system in a
      concentration-dependent manner. At 100 MUg/ml, PG showed slightly stronger
      superoxide scavenging activity than PM. In an electron spin resonance (ESR)-spin
      trapping method in which the Fenton reaction was used as hydroxyl radical
      generation system, we found that both PM and PG showed potent hydroxyl radical
      scavenging activity to a similar extent. Because PM and PG showed no chelating
      activity on Fe(2+), it was confirmed that PM and PG can directly scavenge
      hydroxyl radical. No significant scavenging activity of PM and PG toward hydrogen
      peroxide was observed. Interestingly, the macrophage-stimulation activity of PG
      as measured by nitric oxide (NO)-production from mouse macrophage cell line
      RAW264.7 cells was evidently stronger than that of PM. Our results suggest that
      RAW264.7 cells might be able to distinguish the conformational differences
      between PM and PG, and respond differently to them, whereas the effects of such
      structural differences between PM and PG on the radical scavenging activities may
      not be so significant.

PMID- 22402101
TI  - Synthesis of N-homobicyclic dideoxynucleoside analogues.
AB  - Syntheses of six N-homobicyclic dideoxynucleoside analogues are described. The
      reaction of mannose diacetonide with trimethylsulfoxonium iodide gave a mixture
      of diastereomeric hydroxymethyl mannose diacetonides in a ratio of 2:5, which was
      separated by fractional crystallization. The two stereoisomers were converted to
      bicyclic furanolactols each of which was coupled with three nucleoside bases.
      Further debenzylations gave the six target N-homobicyclic dideoxynucleosides.

PMID- 22402102
TI  - Koenigs-Knorr reaction of fusel alcohols with methyl (1-bromo-2,3,4-tri-O-acetyl
      alpha-D-glucopyranosid)uronate leading to the protected alkyl glucuronides
      crystal structures and high resolution 1H and 13C NMR data.
AB  - Crystal structures and high resolution (1)H and (13)C NMR spectral data for
      methyl (alkyl 2,3,4-tri-O-acetyl-beta-D-glucopyranosid)uronates (alkyl=methyl,
      ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, i-butyl, n-pentyl, 2-methyl-1
      butyl and 3-methyl-1-butyl) are presented.

PMID- 22402103
TI  - [Paediatric ventricular assist: a healthcare reality with an encouraging future].

PMID- 22402104
TI  - Protein analysis through Western blot of cells excised individually from human
      brain and muscle tissue.
AB  - Comparing protein levels from single cells in tissue has not been achieved
      through Western blot. Laser capture microdissection allows for the ability to
      excise single cells from sectioned tissue and compile an aggregate of cells in
      lysis buffer. In this study we analyzed proteins from cells excised individually
      from brain and muscle tissue through Western blot. After we excised individual
      neurons from the substantia nigra of the brain, the accumulated surface area of
      the individual cells was 120,000, 24,000, 360,000, 480,000, 600,000 MUm2. We used
      an optimized Western blot protocol to probe for tyrosine hydroxylase in this cell
      pool. We also took 360,000 MUm2 of astrocytes (1700 cells) and analyzed the
      specificity of the method. In muscle we were able to analyze the proteins of the
      five complexes of the electron transport chain through Western blot from 200
      human cells. With this method, we demonstrate the ability to compare cell
      specific protein levels in the brain and muscle and describe for the first time
      how to visualize proteins through Western blot from cells captured individually.

PMID- 22402105
TI  - Phylogenetic study of Baylisascaris schroederi isolated from Qinling subspecies
      of giant panda in China based on combined nuclear 5.8S and the second internal
      transcribed spacer (ITS-2) ribosomal DNA sequences.
AB  - The nuclear ribosomal DNA (rDNA) region spanning 5.8S rDNA and the second
      internal transcribed spacer (ITS-2) of Baylisascaris schroederi isolated from the
      Qinling subspecies of giant panda in Shaanxi Province, China were amplified and
      sequenced. Sequence variations in the two rDNA regions within B. schroederi and
      among species in the family Ascarididae were examined. The lengths of B.
      schroederi 5.8S and ITS-2 rDNA sequences were 156 bp and 327 bp, respectively,
      and no nucleotide variation was found in these two rDNA regions among the 20 B.
      schroederi samples examined, and these ITS-2 sequences were identical to that of
      B. schroederi isolated from giant panda in Sichuan province, China. The inter
      species differences in 5.8S and ITS-2 rDNA sequences among members of the family
      Ascarididae were 0-1.3% and 0-17.7%, respectively. Phylogenetic relationships
      among species in the Ascarididae were re-constructed by Bayesian inference
      (Bayes), maximum parsimony (MP), and maximum likelihood (ML) analyses, based on
      combined sequences of 5.8S and ITS-2 rDNA. All B. schroederi samples clustered
      together and sistered to B. transfuga with high posterior probabilities/bootstrap
      values, which further confirmed that nematodes isolated from the Qinling
      subspecies of giant panda in Shaanxi Province, China represent B. schroederi.
      Because of the large number of ambiguously aligned sequence positions (difficulty
      of inferring homology by positions), ITS-2 sequence alone is likely unsuitable
      for phylogenetic analyses at the family level, but the combined 5.8S and ITS-2
      rDNA sequences provide alternative genetic markers for the identification of B.
      schroederi and for phylogenetic analysis of parasites in the family Ascarididae.

PMID- 22402106
TI  - Characterization of two cysteine proteases secreted by Blastocystis ST7, a human
      intestinal parasite.
AB  - Blastocystis spp. are unicellular anaerobic intestinal parasites of both humans
      and animals and the most prevalent ones found in human stool samples. Their
      association with various gastrointestinal disorders raises the questions of its
      pathogenicity and of the molecular mechanisms involved. Since secreted proteases
      are well-known to be implicated in intestinal parasite virulence, we intended to
      determine whether Blastocystis spp. possess such pathogenic factors. In silico
      analysis of the Blastocystis subtype 7 (ST7) genome sequence highlighted 22 genes
      coding proteases which were predicted to be secreted. We characterized the
      proteolytic activities in the secretory products of Blastocystis ST7 using
      specific protease inhibitors. Two cysteine proteases, a cathepsin B and a
      legumain, were identified in the parasite culture supernatant by gelatin
      zymographic SDS-PAGE gel and MS/MS analysis. These proteases might act on
      intestinal cells and disturb gut function. This work provides serious molecular
      candidates to link Blastocystis spp. and intestinal disorders.

PMID- 22402107
TI  - Abdominal extraosseous lesions of multiple myeloma: imaging findings.

PMID- 22402108
TI  - A review of pneumatosis intestinalis in the setting of systemic cancer
      treatments, including tyrosine kinase inhibitors.
AB  - PURPOSE: Pneumatosis intestinalis is a radiologic diagnosis that manifests in a
      variety of clinical settings. We report 4 cases of pneumatosis intestinalis in
      patients undergoing cancer treatments that included cytotoxic agents and/or
      tyrosine kinase inhibitors. These reports aim to provide insight into the
      clinical interpretation and pathogenesis of pneumatosis intestinalis in the
      setting of cancer treatments and demonstrate a potential association with
      tyrosine kinase inhibitors. METHODS: Radiologists responsible for the
      interpretation of adult imaging at our tertiary care centre were surveyed to
      identify cases of pneumatosis intestinalis arising in the midst of cancer
      treatment. The case histories were reviewed by physicians with expertise in
      cancer treatment. RESULTS: Four cases of chemotherapy-related pneumatosis
      intestinalis were identified. The diagnosis was made in 1 patient during
      investigations undertaken for non-life-threatening abdominal symptoms and
      incidentally in 2 patients by abdominal imaging used to measure chemotherapy
      response. A fourth patient presented in a life-threatening manner, and abdominal
      imaging was symptom guided. Interestingly, 3 of the 4 patients were receiving
      treatments that included a tyrosine kinase inhibitor, and this agent was the only
      identifiable potential etiology in 1 patient. CONCLUSIONS: The significance of
      pneumatosis intestinalis arising during cancer treatments is difficult to
      interpret because of the complex nature of the diseases and the treatments that
      often include combinations of cytotoxic agents and/or novel therapies. These
      reports demonstrate the importance of classifying this radiologic finding
      according clinical severity rather than etiology and underscore the need for
      continued observation for unexplained adverse effects when using novel therapies.

PMID- 22402109
TI  - Multifocal carcinoma in situ of the upper tract is associated with high risk of
      bladder cancer recurrence.

PMID- 22402111
TI  - Objective evaluation of bone metastases in prostate cancer: to what end?

PMID- 22402112
TI  - Is radiofrequency ablation for small kidney tumors ready for prime time?

PMID- 22402113
TI  - Estrogen-independent effects of ER-alpha36 in ER-negative breast cancer.
AB  - Estrogen receptor-alpha 36 (ER-alpha36) is a variant of ER-alpha that has been
      found to be expressed in conventional ER (ER-alpha66)-negative breast cancer cell
      lines and human breast cancer samples. In this study, we found that, using
      immunohistochemical study, ER-alpha36 expression was significantly higher in ER
      negative tumors than in ER-positive tumors although the expression was not
      associated with other clinicopathological characteristics. We then constructed an
      ER-alpha36-specific microRNA hairpin vector and established stable ER-alpha36
      knockdown cells, and found that the knockdown cells were more sensitive to
      paclitaxel; the c-Jun N-terminal kinase pathway appeared to be involved in the
      mechanism. Downregulation of ER-alpha36 also resulted in decreased migration and
      invasion. These changes were estrogen independent. Our findings indicated that
      target ER-alpha36 may be a strategy for treating ER-negative breast cancers.

PMID- 22402114
TI  - Retroperitoneal white adipose tissue mitochondrial function and adiponectin
      expression in response to ovariectomy and 17beta-estradiol replacement.
AB  - Sexual dimorphism has been previously found both in mitochondrial biogenesis and
      function and in adiponectin expression of retroperitoneal WAT. However, little is
      known about the E2 effects on WAT mitochondrial function. Accordingly, the aim of
      this study was to examine in greater depth the role of estrogens in sexual
      dimorphism. This was accomplished by studying the effects of ovariectomy and E2
      replacement on retroperitoneal WAT mitochondrial function. Fourteen-week-old
      female and ovariectomized (OVX) female Wistar rats were used in this study. The
      ovariectomy was performed at 5 weeks of age and at 10 weeks of age OVX rats were
      divided into two experimental groups: OVX, and OVX treated with 17beta-estradiol
      (E2) (OVX+E2). Subcutaneous injections of E2 (10 MUg/kg/48 h) were administered
      to the OVX+E2 rats for 4 weeks previous to the sacrifice whereas OVX rats were
      treated only with the vehicle. Levels of the main markers for mitochondrial
      biogenesis and function and those representatives of the antioxidant defense
      system and insulin sensitivity were determined. Additionally, the mRNA levels of
      the alpha and beta estrogen receptors and of some adipocyte differentiation
      markers were studied. Our results indicate that retroperitoneal WAT was able to
      adapt itself to ovariectomy without any changes in mitochondrial function markers
      or for the adiponectin levels. However, E2 supplementation led to an unexpected
      decrease in: TFAM protein levels, in LPL, PPARgamma and adiponectin gene
      expression and in the systemic HMW adiponectin levels. This decrease is probably
      due to the down-regulation of the ERalpha mRNA expression to avoid an over
      stimulation by E2.

PMID- 22402115
TI  - In vivo precision of dual-energy X-ray absorptiometry-derived hip structural
      analysis in adults.
AB  - Precision is integral to the monitoring of bone mineral density (BMD) change
      using dual-energy X-ray absorptiometry (DXA). Hip structural analysis (HSA) is a
      relatively recent method of assessing cross-sectional geometrical strength from
      the 2-dimensional images produced by DXA scans. By performing serial scans, we
      evaluated the in vivo precision of DXA-derived HSA in adults using a GE Lunar
      iDXA absorptiometer (GE Medical Systems, Madison, WI) in males and females
      (n=42), mean age of 34.5 (standard deviation [SD]: 8.5; range: 19.3-52.6)yr with
      a heterogeneous sample. Two consecutive intelligent DXA (iDXA) scans with
      repositioning of both femurs were conducted for each participant. The coefficient
      of variation, root-mean-square (RMS) averages of SD, and hence the least
      significant change (95%) were calculated. We found a high level of precision for
      BMD measurements of both the total hip and femoral neck, with RMS-SD=0.006 and
      0.010 g/cm(2) and percent coefficient of variation (%CV)=0.52% and 0.94%,
      respectively. We also found good precision for HSA-derived geometrical
      properties, including sectional modulus, cross-sectional moment of inertia, and
      cross-sectional area, with %CV (average of the left and right sides) at 4.48%,
      3.78%, and 3.13%, respectively. Precision was poorer for buckling ratio and
      femoral strength index with %CV 28.5% and 9.25%, respectively. The iDXA provides
      high precision for BMD measurements and with varying levels of precision for HSA
      geometrical properties.

PMID- 22402116
TI  - Increase in android fat mass with age in healthy women with normal body mass
      index.
AB  - Body fat distribution is gender specific: men tend to accumulate adipose tissue
      in the android region, whereas women tend to do so in the gynoid region. The aim
      of the study was to assess total fat mass (TFM), android fat (AF), and gynoid fat
      (GF) mass in a selected group of healthy adult women with normal body mass index
      (BMI) to evaluate variations in fat distribution. Seventy-seven women (20--69yr
      of age) with BMI values between >=18.5 and <=24.9kg/m(2) were included. TMF, AF,
      GF, and the AF to GF ratio (A:G) were assessed using dual-energy X-ray
      absorptiometry. Results showed an increase in AF after the fifth decade of life
      (D), which reached statistical significance in the sixth and seventh decades
      (p<0.05--0.008), a 33% increase in kg of AF between the fourth and seventh and a
      20% increase in A:G between the third and the seventh, with no significant
      changes in TFM and GF. In normal BMI women, age appears to be associated with
      changes in fat mass distribution with an increase in AF, which might have
      potential deleterious health consequences, after the fifth D.

PMID- 22402117
TI  - DXA femoral neck strength analysis in Chinese overweight and normal weight
      adolescents.
AB  - The aim of this study was to compare femoral neck (FN) strength in Chinese
      overweight adolescents with gender-matched normal weight controls and investigate
      the relationship of total body soft tissue composition (lean and fat masses) to
      indices of FN strength. Dual-energy X-ray absorptiometry (DXA) measurements of
      the proximal femur and total body were made in 65 Chinese overweight adolescents
      and 89 gender-matched normal weight controls using Lunar Prodigy DXA bone
      densitometer (GE Healthcare, Madison, WI). FN bone mineral density (BMD), total
      body lean mass, fat mass, and bone mineral content (BMC) were measured. Using FN
      BMD values derived from DXA measurements, hip structural analysis (HSA) was
      performed using Lunar enCORE (GE Healthcare), version 10.5 software. Structural
      parameters derived by HSA were bone cross-sectional area (CSA), cross-sectional
      moment of inertia (CSMI), and the section modulus (Z). Data were analyzed by
      Student's t-test, Pearson correlation coefficients (r), and one-way analysis of
      covariance (ANCOVA). Overweight boys and girls had higher body weight, lean mass,
      fat mass, and body mass index (p<0.001) than normal controls. CSA, CSMI, and Z
      were higher in overweight groups compared with controls (p<0.05). Lean mass
      correlated well with all HSA parameters (range of r: 0.501--0.714) for both
      genders. ANCOVA test showed no significant differences between overweight and
      normal weight groups regarding HSA variables in both genders after adjustment for
      lean mass. However, the differences remain significant after adjustment for fat
      mass in boys but not in girls. This study supports the conclusion that overweight
      individuals have greater hip neck strength in comparison with normal weight
      controls in Chinese adolescents. Lean mass is a major determinant for FN
      strength.

PMID- 22402118
TI  - Bone quality and nutritional status in children with congenital heart defects.
AB  - The aim of this study was to evaluate bone quality and nutritional status in
      children with congenital heart defects (CHDs) using quantitative ultrasound. A
      cross-sectional study was designed. A population-based sample of 75 children with
      CHD (age: 0--6yr) from the Department of Pediatric Cardiology at the National
      Cardiology Institute "Ignacio Chavez" was compared with 106 healthy children
      during 2009. Weight and height were determined in both groups; bone status was
      measured at the radius and tibia as speed of sound (SOS). Nutritional status was
      defined according to the Waterloo and Gomez index. Chi-square test, Student's t
      test, and analysis of variance were used to determine the statistical
      differences. A linear regression analysis adjusted by age, weight, height, type
      of CHD, and birth weight was made. Both groups were similar in sex distribution,
      prematurity, and birth weight. Acyanotic cardiopathy with increased pulmonary
      flow was the most frequent (61.3%). Prevalence of malnutrition was higher in CHD
      group compared with healthy children (p<0.001), and radius SOS was lower in
      children with CHD compared with healthy children (3484+/-180 vs 3575+/-159m/s,
      respectively; 95% confidence interval: 39.8--143; p=0.001). A positive
      correlation was found between CHD and reduced SOS in the adjusted linear
      regression model, r2=0.455 (p<0.001). Children with CHD have lower SOS radius
      values compared with healthy children, suggesting reduced bone quality regardless
      of the nutritional status.

PMID- 22402119
TI  - Peak bone mineral density and its determinants in an Asian Indian population.
AB  - Data on peak bone mineral density (BMD) and its determinants in Asian Indians are
      limited. We studied the peak BMD and its determinants in Asian Indians. A total
      of 1137 young (age: 25--35yr) healthy volunteers of either sex (558 men and 579
      women) were recruited for dietary evaluation, analyses of serum calcium,
      inorganic phosphorus, alkaline phosphatase, 25-hydroxyvitamin D [25(OH)D], and
      intact parathyroid hormone (iPTH) levels, and measurement of BMD with dual-energy
      X-ray absorptiometry. In men and women, peak bone mass (PBM) at the femoral neck,
      femoral trochanter, total femur, and lumbar spine was achieved between 25 and
      30yr of age, whereas PBM at the femoral intertrochanter occurred between 30 and
      35yr of age. Peak BMD was lower than that of Caucasians by 15.2--21.1% in men and
      14.4--20.6% in women. On stepwise multiple regression, height and weight were the
      most consistent predictors of BMD at all sites in both groups. In men, 25(OH)D
      positively predicted BMD at the hip, whereas in women, serum iPTH negatively
      predicted BMD at the femoral trochanter and total femur. The study concluded that
      Asian Indians have significantly lower peak BMD than Caucasians and that weight
      and height are the most consistent predictors of BMD at all sites in both men and
      women.

PMID- 22402120
TI  - Obesity increases precision errors in dual-energy X-ray absorptiometry
      measurements.
AB  - The precision errors of dual-energy X-ray absorptiometry (DXA) measurements are
      important for monitoring osteoporosis. This study investigated the effect of body
      mass index (BMI) on precision errors for lumbar spine (LS), femoral neck (NOF),
      total hip (TH), and total body (TB) bone mineral density using the GE Lunar
      Prodigy. One hundred two women with BMIs ranging from 18.5 to 45.9 kg/m(2) were
      recruited. Participants had duplicate DXA scans of the LS, left hip, and TB with
      repositioning between scans. Participants were divided into 3 groups based on
      their BMI and the percentage coefficient of variation (%CV) calculated for each
      group. The %CVs for the normal (<25 kg/m(2)) (n=48), overweight (25-30 kg/m(2))
      (n=26), and obese (>30 kg/m(2)) (n=28) BMI groups, respectively, were LS BMD:
      0.99%, 1.30%, and 1.68%; NOF BMD: 1.32%, 1.37%, and 2.00%; TH BMD: 0.85%, 0.88%,
      and 1.06%; TB BMD: 0.66%, 0.73%, and 0.91%. Statistically significant differences
      in precision error between the normal and obese groups were found for LS
      (p=0.0006), NOF (p=0.005), and TB BMD (p=0.025). These results suggest that
      serial measurements in obese subjects should be treated with caution because the
      least significant change may be larger than anticipated.

PMID- 22402121
TI  - Fracture of vertebral spine because of an unusual cause of osteoporosis in a
      young male patient.

PMID- 22402122
TI  - Characterization of human serum butyrylcholinesterase in rhesus monkeys:
      behavioral and physiological effects.
AB  - The effects of a large dose of human serum butyrylcholinesterase (HuBChE) were
      evaluated in rhesus monkeys using a serial-probe recognition (SPR) task designed
      to assess attention and short-term memory. Each monkey received an intravenous
      injection of 150 mg (105,000 U or 30 mg/kg) of HuBChE 60 min prior to testing on
      the SPR task. Concurrent with the cognitive-behavioral assessment, blood was
      collected at various time points throughout the study and was analyzed for
      acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities, anti
      BChE antibody production and gross clinical pathology (i.e., complete blood count
      and clinical chemistry panel). HuBChE revealed a peak blood activity of 227 U/ml
      at 5 min after intravenous injection and a mean residence time of approximately
      72 h. No cognitive-behavioral decrements of any kind in SPR performance and no
      toxic signs in clinical pathology were detected in any of the blood assays during
      the 5 weeks of observation. Anti-HuBChE antibodies peaked at about 14 days after
      injection, with no concomitant behavioral changes. These results demonstrate the
      behavioral and physiological safety of HuBChE in rhesus monkeys and support its
      development as a bioscavenger for the prophylaxis of chemical warfare agent
      toxicity in humans.

PMID- 22402123
TI  - ERK inhibition overcomes acquired resistance to MEK inhibitors.
AB  - The RAS/RAF/MEK pathway is activated in more than 30% of human cancers, most
      commonly via mutation in the K-ras oncogene and also via mutations in BRAF.
      Several allosteric mitogen-activated protein/extracellular signal-regulated
      kinase (MEK) inhibitors, aimed at treating tumors with RAS/RAF pathway
      alterations, are in clinical development. However, acquired resistance to these
      inhibitors has been documented both in preclinical and clinical samples. To
      identify strategies to overcome this resistance, we have derived three
      independent MEK inhibitor-resistant cell lines. Resistance to allosteric MEK
      inhibitors in these cell lines was consistently linked to acquired mutations in
      the allosteric binding pocket of MEK. In one cell line, concurrent amplification
      of mutant K-ras was observed in conjunction with MEK allosteric pocket mutations.
      Clonal analysis showed that both resistance mechanisms occur in the same cell and
      contribute to enhanced resistance. Importantly, in all cases the MEK-resistant
      cell lines retained their addiction to the mitogen-activated protein kinase
      (MAPK) pathway, as evidenced by their sensitivity to a selective inhibitor of the
      ERK1/2 kinases. These data suggest that tumors with acquired MEK inhibitor
      resistance remain dependent on the MAPK pathway and are therefore sensitive to
      inhibitors that act downstream of the mutated MEK target. Importantly, we show
      that dual inhibition of MEK and ERK by small molecule inhibitors was synergistic
      and acted to both inhibit the emergence of resistance, as well as to overcome
      acquired resistance to MEK inhibitors. Therefore, our data provide a rationale
      for cotargeting multiple nodes within the MAPK signaling cascade in K-ras mutant
      tumors to maximize therapeutic benefit for patients.

PMID- 22402124
TI  - JAK-STAT and JAK-PI3K-mTORC1 pathways regulate telomerase transcriptionally and
      posttranslationally in ATL cells.
AB  - Adult T-cell leukemia (ATL) is a heterogeneous tumor that is resistant to
      chemotherapy. Telomerase activity plays a critical role in tumorigenesis and is
      associated with the prognosis of ATL patients. Interleukin (IL)-2 commonly
      promotes tumor growth in chronic ATL cells. The signaling pathways involved in IL
      2-regulated telomerase activation were studied in ATL cells derived from chronic
      ATL patients. IL-2 challenge enhanced tyrosine phosphorylation of Janus-activated
      kinase (JAK)1-3 and STAT5, and induced JAK1 and JAK2 to associate with STAT5 in
      IL-2-dependent ATL cells. Chromatin immunoprecipitation assays revealed that
      STAT5 directly bound to the human telomerase reverse transcriptase (hTERT)
      promoter. STAT5 short interfering RNA inhibited hTERT transcription in IL-2
      stimulated ATL cells. Inhibitors of PI3K, HSP90, and mTOR reduced IL-2-induced
      hTERT mRNA, protein expression, and telomerase activity. AKT, HSP90, mTOR, S6
      kinase, and hTERT immunoprecipitate from IL-2-stimulated cells contained
      telomerase activity, suggesting that hTERT directly interacts with, and is
      regulated by, these proteins. Binding of the p85 regulatory subunit of PI3K to
      JAK2 was enhanced in an IL-2-dependent manner, indicating that JAK2 propagates
      activation signals from the IL-2 receptor and links hTERT activation to both the
      STAT5 and PI3K pathways. Finally, IL-2-induced activation of telomerase and STAT5
      was observed in primary leukemic cells. These results indicate that IL-2
      stimulation induces hTERT activation through the JAK/STAT pathway and the
      JAK/PI3K/AKT/HSP90/mTORC1 pathway in IL-2-responsive ATL cells. These signaling
      proteins represent novel and promising molecular therapeutic targets for IL-2
      dependent ATL.

PMID- 22402125
TI  - miRNA-29b suppresses prostate cancer metastasis by regulating epithelial
      mesenchymal transition signaling.
AB  - Prostate cancer remains the second leading cause of cancer deaths among American
      men. Early diagnosis increases survival rate in patients; however, treatments for
      advanced disease are limited to hormone ablation techniques and palliative care.
      Thus, new methods of treatment are necessary for inhibiting prostate cancer
      disease progression. Here, we have shown that miRNA-29b (miR-29b) expression was
      lower in prostate cancer cells (PC3 and LNCaP) as compared with immortalized
      prostate epithelial cells. Between these two prostate cancer cell lines,
      metastatic prostate cancer PC3 cells displayed lower expression of miR-29b. We
      also observed a significant downregulation of miR-29b expression in human
      prostate cancer tissues as compared with patient-matched nontumor tissues. PC3
      cells ectopically expressing miR-29b inhibited wound healing, invasiveness, and
      failed to colonize in the lungs and liver of severe combined immunodeficient mice
      after intravenous injection, while PC3 cells expressing a control miRNA displayed
      metastasis. Epithelial cell marker E-cadherin expression was enhanced miR-29b
      transfected in prostate cancer cells as compared with cells expressing control
      miRNA. On the other hand, N-cadherin, Twist, and Snail expression was
      downregulated in PC3 cells expressing miR-29b. Together these results suggested
      that miR-29b acts as an antimetastatic miRNA for prostate cancer cells at
      multiple steps in a metastatic cascade. Therefore, miR-29b could be a potentially
      new attractive target for therapeutic intervention in prostate cancer.

PMID- 22402126
TI  - Hyperactivation of 4E-binding protein 1 as a mediator of biguanide-induced
      cytotoxicity during glucose deprivation.
AB  - Biguanides, including metformin, buformin, and phenformin, are potential
      antitumorigenic agents and induce cell death during glucose deprivation, a cell
      condition that occurs in the tumor microenvironment. Here, we show that this
      selective killing of glucose-deprived cells is coupled with hyperactivation of
      eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), a negative regulator
      of translation initiation. We found, in fact, that the 4E-BP1 hyperactivation led
      to failure of the unfolded protein response (UPR), an endoplasmic reticulum
      originated stress signaling pathway for cell survival. We also found that the 4E
      BP1-mediated UPR inhibition occurred through a strong inhibition of the mTOR
      signaling pathway, a proven antitumor target. Importantly, the 4E-BP1
      hyperactivation can be also seen in xenografted cancer cells through an in vivo
      biguanide treatment. Our findings indicate that antitumor action of biguanides
      can be mediated by 4E-BP1 hyperactivation, which results in UPR inhibition and
      selective cell killing when glucose is withdrawn.

PMID- 22402127
TI  - Atmospheric pressure gas chromatography coupled to quadrupole-time of flight mass
      spectrometry as a powerful tool for identification of non intentionally added
      substances in acrylic adhesives used in food packaging materials.
AB  - Acrylic adhesives are used to manufacture multilayer laminates that are used in
      food packaging to form the geometric shape of the package as well as to stick
      labels on the packages. Once applied on the packaging adhesives can supply
      potential migrants that could endanger the packaged food. Adhesives are complex
      matrices where intentionally and non intentionally added substances are present,
      but the identification of the migrants is required by law. In this study
      atmospheric pressure gas chromatography coupled to a quadrupole hyphenated to a
      time of flight mass spectrometer (APGC-MS/Q-TOF) has been explored for
      identification of unknowns coming from three different acrylic adhesives. The
      results are compared to those obtained by conventional GC-MS-Q (quadrupole).
      Sixteen compounds were identified by GC-MS/Q and five of them were confirmed by
      APGC-MS/Q-TOF as their molecular ions were found. Moreover, additional three new
      compounds were identified and their structure was elucidated working with the
      spectra obtained by APGC-MS/Q-TOF. This finding was very relevant as these
      compounds were biocides suspected to be allergenic and cytotoxic in humans.
      Migration studies were carried out using Tenax as solid food simulant and the
      results showed that the three acrylic adhesives tested in this work were safe for
      being used in food packaging materials since the migration of compounds
      previously identified was below the limit established in the current legislation.

PMID- 22402128
TI  - Determination of triazine herbicides in cereals using dynamic microwave-assisted
      extraction with solidification of floating organic drop followed by high
      performance liquid chromatography.
AB  - A simple and cost-effective method of dynamic microwave-assisted extraction
      (DMAE) combined with solidification of floating organic drop (SFO) was developed
      for determining the five triazine herbicides in cereals. The approach combines
      the advantages of DMAE and SFO technique, and up to 15 samples can be treated
      simultaneously in 16 min. Firstly, triazine herbicides were extracted with 1 mL
      of methanol containing 90 MUL of 1-dodecanol and following with 10 mL of water
      under the action of microwave energy. After that, 1.5 g sodium chloride was added
      into the obtained extract, and the mixture was centrifuged and cooled. The 1
      dodecanol drop which contained the target analytes was solidified and transferred
      for analysis by HPLC-UV. Limits of detection of the five triazines obtained were
      in the range of 1.1-1.5 ng g(-1). Relative standard deviations of intra- and
      inter-day tests ranging from 5% to 7% were obtained. The method was successfully
      applied to the analysis of ten cereals and the recoveries of the triazines for
      the spiked samples were in the range of 80-102%. The proposed method is an
      alternative approach to the analysis of triazine herbicides in complex solid
      samples, being more rapid and simpler compared with the traditional extraction
      method.

PMID- 22402129
TI  - Derivatization and liquid chromatography-UV-tandem mass spectrometric analysis of
      perfluorinated carboxylic acids.
AB  - The presence of perfluorocarboxylates (PFCAs) in the environment is of increasing
      concern due to their possible toxicity to humans and bioaccumulation in
      organisms. PFCAs are frequently found in river water, sediment and organisms and
      sometimes even in groundwater. In order to quantitatively determine these PFCAs,
      a fast derivatization coupled with a liquid chromatography-ultraviolet detector
      electrospray ionization-tandem mass spectrometry (LC-UV-ESI-MS/MS) method was
      developed. The PFCAs were quantitatively converted to their corresponding
      phenacyl esters using p-bromophenacyl bromide as the derivatization reagent.
      Under optimized reaction conditions, the conversion yield of the PFCAs ranged
      from 86 to 92% with low %RSD. The typical derivatization product (p-bromophenacyl
      bromide perfluorooctanoate) was characterized by (1)H NMR, (13)C NMR, FT-IR and
      mass spectrometry. UPLC with a BEH C18 column and CAN/H(2)O (8/2, v/v) as a
      mobile phase were used to separate the derivatives. The analytes were completely
      eluted within 6 min and multidimensional detection using UV at 260 nm and ESI-MRM
      in the negative ion mode were carried out. Bromide isotopic characteristic
      fragment ions appeared in the first Q1 scans, and four daughter ions of the MRMs
      at m/z [M-H-222](-), [M-H-250](-), [M-H-278](-) and [M-H-316](-) were used for
      quantification and confirmation. The mass spectral information ensured accurate
      identification of the analytes even when the sample matrices were complex. The
      method successfully eliminated the PFCAs background problems originating from
      polymeric parts in liquid chromatographic systems. The LODs of the method were
      lower than 5 ng mL(-1), and the relative standard deviation (RSD%) values ranged
      from 5.2 to 9.8%. The method was successfully applied for the quantification of
      PFCAs in river water contaminated by industrial wastewater, and this indicated
      that the method was useful in the determination of PFCAs in environmental
      samples.

PMID- 22402130
TI  - Evaluation of sulfonated graphene sheets as sorbent for micro-solid-phase
      extraction combined with gas chromatography-mass spectrometry.
AB  - This report describes the use of sulfonated graphene sheets as sorbent in micro
      solid-phase extraction (MU-SPE), together with gas chromatography-mass
      spectrometry, for the determination of polycyclic aromatic hydrocarbons (PAHs) in
      water. In this study, for the first time, graphene sheets were used as a sorbent
      material for this mode of microextraction. The modified graphene sheets were
      characterized by transmission electron microscopy, Fourier transform infrared
      spectroscopy, and elemental analysis. MU-SPE parameters such as extraction time,
      desorption time and desorption solvent were optimized. The method showed good
      precision, reproducibility and linear response for PAH analysis over a
      concentration range of 0.05-100 MUg/L for naphthalene and 0.01-100 MUg/L for the
      remaining PAHs (acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene
      and pyrene) with coefficient of determination (r(2)) of higher than 0.992. Limits
      of detection of from 0.8 to 3.9 ng/L for 7 PAHs were achieved. The developed
      method was successfully applied to determine PAHs in river water samples.

PMID- 22402131
TI  - A small molecule focal adhesion kinase (FAK) inhibitor, targeting Y397 site: 1-(2
      hydroxyethyl)-3, 5, 7-triaza-1-azoniatricyclo [3.3.1.1(3,7)]decane; bromide
      effectively inhibits FAK autophosphorylation activity and decreases cancer cell
      viability, clonogenicity and tumor growth in vivo.
AB  - Focal adhesion kinase (FAK) is a protein tyrosine kinase that is overexpressed in
      most solid types of tumors and plays an important role in the survival signaling.
      Recently, we have developed a novel computer modeling combined with a functional
      assay approach to target the main autophosphorylation site of FAK (Y397). Using
      these approaches, we identified 1-(2-hydroxyethyl)-3, 5, 7-triaza-1
      azoniatricyclo [3.3.1.1(3,7)]decane; bromide, called Y11, a small molecule
      inhibitor targeting Y397 site of FAK. Y11 significantly and specifically
      decreased FAK autophosphorylation, directly bound to the N-terminal domain of
      FAK. In addition, Y11 decreased Y397-FAK autophosphorylation, inhibited viability
      and clonogenicity of colon SW620 and breast BT474 cancer cells and increased
      detachment and apoptosis in vitro. Moreover, Y11 significantly decreased tumor
      growth in the colon cancer cell mouse xenograft model. Finally, tumors from the
      Y11-treated mice demonstrated decreased Y397-FAK autophosphorylation and
      activation of poly (ADP ribose) polymerase and caspase-3. Thus, targeting the
      major autophosphorylation site of FAK with Y11 inhibitor is critical for
      development of cancer therapeutics and carcinogenesis field.

PMID- 22402132
TI  - Genetic variation in MUC1, MUC2 and MUC6 genes and evolution of gastric cancer
      precursor lesions in a long-term follow-up in a high-risk area in Spain.
AB  - In order to assess whether inherited genetic variability in the mucin genes
      associates with the evolution of gastric cancer precursor lesions (GCPLs), we
      genotyped 22 tagSNPs in MUC1, MUC6 and MUC2 genes of 387 patients with GCPLs that
      had been followed up for 12.8 years. According to the diagnosis at recruitment
      and at the end of follow-up, the lesions did not change in 43.1% of the patients,
      regressed in 28.7% and progressed in 28.2%. Three SNPs in the 3'-moiety of MUC2
      were significantly associated with a decreased risk of progression of the
      lesions, whereas another four SNPs, located at the 5'-moiety, were found to be
      significantly associated either with increased [one single-nucleotide
      polymorphism (SNP)] or decreased (three SNPs) probability of regression.
      Stratified analysis indicated that significance was maintained only in those
      subjects positive for Helicobacter pylori infection and in those not consuming
      non-steroidal anti-inflammatory drugs, which were found protective against lesion
      progression. Haplotype analyses indicated the presence of two haplotypes, one in
      each moiety of the gene, that were significantly associated with decreased risk
      of progression of the lesions [odds ratio (OR) = 0.49 and 0.46; 95% confidence
      interval (CI) = 0.28-0.85 and 0.25-0.86, respectively]. The 5'-end haplotype was
      also associated with increased probability of regression (OR = 1.67; 95% CI =
      1.02-2.73), altogether suggesting a protective role against progression of the
      precancerous lesions. No significant association was found with variants in MUC1
      and MUC6 genes. These results indicate, for the first time, that genetic
      variability in MUC2 is associated with evolution of GCPLs, especially in H.pylori
      infected patients, suggesting a role of this secreted mucin in gastric
      carcinogenesis.

PMID- 22402133
TI  - Naturally occurring variant of mouse apolipoprotein A-I alters the lipid and HDL
      association properties of the protein.
AB  - Plasma HDL levels are inversely associated with atherosclerosis. Inbred mouse
      strains differ in plasma HDL levels and susceptibility to atherosclerosis.
      Atherosclerosis-susceptible C57BL/6J mice possess plasma HDL levels 2-fold lower
      than atherosclerosis-resistant FVB/NJ mice. Polymorphisms have been previously
      identified between the two mouse strains in the major HDL apolipoproteins, ApoA-I
      and ApoA-II, which may affect their function on HDL. To begin to understand the
      HDL differences, we here report on a detailed comparison of the lipid-associated
      functions of the two mouse ApoA-I proteins. We demonstrate that these
      polymorphisms significantly alter the protein self-association properties, the
      ability of the proteins to clear lipid micelles from solution, and their binding
      affinity for mature mouse HDL. The changes in lipid binding do not appear to
      alter the ability of the protein to promote cholesterol efflux from cells or the
      formation of nascent HDL from primary hepatocytes. These apolipoprotein
      polymorphisms do not change the rate at which HDL protein or cholesterol are
      catabolized in vivo. Although the presence of the polymorphisms in ApoA-I alters
      important factors in HDL formation, the basis for the differences in the HDL
      plasma levels observed in the various mouse strains is more complex and requires
      additional investigation.

PMID- 22402134
TI  - A meta-analysis of receptor for advanced glycation end products gene: four well
      evaluated polymorphisms with diabetes mellitus.
AB  - Genetic association studies on the gene encoding receptor for advanced glycation
      end products (RAGE) and diabetes mellitus have reported conflicting results. To
      evaluate the association of RAGE gene four widely-evaluated polymorphisms (T
      429C, T-374A, Gly82Ser and G1704T) and diabetes mellitus, a meta-analysis was
      conducted. A random-effects model was applied irrespective of between-study
      heterogeneity. There were a total of 5808/3742 (n=14) case-patients/controls
      (studies) for T-429C, 8259/6935 (n=19) for T-374A, 7029/5266 (n=19) for Gly82Ser,
      and 2843/3302 (n=13) for G1704T. Overall results detected no significant
      association of polymorphisms T-429C, T-374A and Gly82Ser with diabetes risk.
      There was a trend toward an increased risk for alleles 1704T relative to 1704G
      (odds ratio [OR]=1.09; 95% confidence interval [CI]: 0.98-1.22; I(2)=0). Subgroup
      analysis by ethnicity indicated that allele 1704T conferred a significantly
      increased risk in East Asians (OR=1.21; 95% CI: 1.04-1.4; I(2)=0) but not in
      Caucasians (OR=0.8; 95% CI: 0.6-1.07; I(2)=0), and that by type of diabetes
      mellitus indicated that association was potentiated exclusively for G1704T with
      diabetic retinopathy (OR=1.24; 95% CI: 1.01-1.51; I(2)=0). No publication bias
      was observed. Our results provide convincing evidence regarding the association
      of RAGE gene 1704T allele with an increased risk of diabetes mellitus, especially
      diabetic retinopathy. Notably, this effect was more pronounced in East Asians.

PMID- 22402135
TI  - [Human and professional aspects of Mr. Pedro Cifuentes Diaz (1881-1960)].
AB  - OBJECTIVES: Reveal some outstanding aspects from the life of Pedro Cifuentes
      Diaz, remarkable personality of Spanish Urology, who served the "Asociacion
      Espanola de Urologia" for 31 years. His personal documental iconographic legacy
      allow us to better recompose his life and human size. MATERIAL AND METHODS:
      Written material and a collection of 64 personal documents that belonged to Pedro
      Cifuentes Diaz obtained from bibliophiles, 5 of which were not accepted as his
      property due to the absence of a compatible context, are analyzed. The content of
      the main publications of the author is contrasted with his cultural environment,
      and the graphic documents are related with the historical happenings. RESULTS:
      Son of a forensic doctor, good student and opponent. Pedro Cifuentes spent his
      entire urologic career heading the service of Urology of the Hospital de la
      Princesa in Madrid from 1910 to 1950. He acquired a solid formation in France and
      developed a long professional life with important charges and distinctions.
      Besides, he underwent great clinic and scientific activity as publicist,
      academic, docent and manager. He was essential in Asociacion Espanola de Urologia
      since its foundation, and conducted its reorganization after Spanish Civil War.
      He built one of the main urologic schools of Spain, where his son Luis Cifuentes
      Delatte highlighted. CONCLUSIONS: Pedro Cifuentes Diaz was a Castilian man,
      inexhaustible worker, liberal academic, communicator and teacher outside the
      university environment. With excellent formation he acquired important
      international projection and professional acceptance; held many and important
      administrative charges, and received multiple awards. He was one of the most
      remarkable figures of Urology in Madrid and Spain during the first half of the
      20(th) Century.

PMID- 22402136
TI  - Combined copeptin and troponin to rule out myocardial infarction in patients with
      chest pain and a history of coronary artery disease.
AB  - PURPOSE: The main objective of this multicentric study was to evaluate the
      additional value of copeptin to conventional cardiac troponin (cTn) for a rapid
      ruling out of acute myocardial infarction (AMI) in patients with acute chest pain
      and a previous history of coronary artery disease (CAD). PATIENTS AND METHOD:
      Patients with a previous history of CAD presenting in the emergency department
      with acute chest pain lasting for 6 hours or less suggestive of non-ST-segment
      elevation AMI and negative cTn were selected. Levels of copeptin were blindly
      measured at presentation. The diagnosis was adjudicated by 2 independent experts
      using all available data including cTn. RESULTS: A total of 451 patients were
      included (mean age, 67+/-14; 330 [73%] men). The adjudicated final diagnosis was
      AMI in 36 (8%) patients, unstable angina in 131 (29%), and other diagnosis in 284
      (63%). A negative cTn combined with a copeptin value lower than 10.7 pmol/L at
      presentation was able to rule out AMI, with a negative predictive value of 98%
      (95% confidence interval, 95%-99%). CONCLUSION: In triage patients with acute
      chest pain lasting for less than 6 hours and a previous history of CAD, the
      combination of copeptin and cTn allows for the ruling out AMI, with a negative
      predictive value greater than 95%.

PMID- 22402137
TI  - Light-emitting diode illuminant and a plastic single-use blade for intubation
      during cardiopulmonary resuscitation: an infant manikin study.

PMID- 22402138
TI  - Toll-like receptor 2 and Toll-like receptor 4 polymorphisms and susceptibility to
      asthma and allergic rhinitis: a case-control analysis.
AB  - The aim of the study was to investigate whether polymorphisms in genes encoding
      Toll-like receptors (TLR2 and TLR4) may modify relative risk for development of
      asthma or allergic rhinitis. The results showed that the genotype and allele
      frequencies of the TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms were not
      significantly different between asthmatic children or allergic rhinitis when
      compared to controls (p>0.05 for each) or even when compared further with IgE
      level. However, it was shown that the mutant allele of TLR2 or TLR4 polymorphisms
      were significantly associated with the moderate-severe group compared to the mild
      group in both atopic asthmatics and allergic rhinitis group (p>0.001 for each).
      In conclusion, our study demonstrates a lack of association of TLR2 and TLR4
      polymorphisms with asthma and allergic rhinitis but suggests significant
      association between these genetic variants and the disease severity.

PMID- 22402139
TI  - Inhibition of hedgehog signalling prevents experimental fibrosis and induces
      regression of established fibrosis.
AB  - OBJECTIVES: Tissue fibrosis is a leading cause of death in patients with systemic
      sclerosis (SSc). Effective antifibrotic treatments are not available. Here, the
      authors investigated inhibition of hedgehog signalling by targeting Smoothened
      (Smo) as a novel antifibrotic approach. METHODS: The activation status of the
      hedgehog pathway was assessed by immunohistochemistry for Gli transcription
      factors and by quantification of hedgehog target genes. Hedgehog signalling was
      inhibited by the selective inhibitor LDE223 and by small interfering RNA against
      Smo in the models of bleomycin-induced dermal fibrosis and in tight-skin-1 mice.
      RESULTS: Hedgehog signalling is activated in SSc and in murine models of SSc.
      Inhibition of Smo either by LDE223 or by small interfering RNA prevented dermal
      thickening, myofibroblast differentiation and accumulation of collagen upon
      challenge with bleomycin. Targeting Smo also exerted potent antifibrotic effects
      in tight-skin-1 mice and did prevent progression of fibrosis and induced
      regression of pre-established fibrosis. CONCLUSIONS: Inhibition of hedgehog
      signalling exerted potent antifibrotic effects in preclinical models of SSc in
      both preventive and therapeutic settings. These findings might have direct
      translational implications because inhibitors of Smo are already available and
      yielded promising results in initial clinical trials.

PMID- 22402140
TI  - A vascular endothelial growth factor deficiency characterises scleroderma lung
      disease.
AB  - OBJECTIVES: Vascular endothelial growth factor (VEGF) is thought to play an
      important role in systemic sclerosis (SSc) pathogenesis. It was found to be
      upregulated in the serum and in the affected skin of scleroderma patients.
      However, its involvement in scleroderma lung disease is not clear. This study
      aimed to evaluate VEGF concentration in the bronchoalveolar lavage fluid (BALF)
      of scleroderma patients with interstitial lung disease, to correlate the cytokine
      levels in plasma and in the lung with pulmonary functional, radiological and
      cellular parameters, and with the progression of lung disease. METHODS: BALF and
      plasma VEGF concentrations were analysed by ELISA in 55 SSc patients with lung
      disease and 17 controls. Cytokine real-time PCR messenger RNA expression in
      alveolar macrophages was assessed. Lung involvement progression was evaluated
      after a 1-year follow-up. RESULTS: VEGF was found to be significantly lower in
      the BALF of scleroderma patients compared with controls. The lowest
      concentrations were observed in SSc patients with alveolitis. A decreased VEGF
      expression in alveolar macrophages was found in SSc patients with alveolitis.
      VEGF concentration in BALF correlated inversely with the ground glass score on
      high-resolution CT and with BALF neutrophil cell count. Moreover, SSc patients
      with a lower VEGF concentration showed a worsening in the interstitial score at
      follow-up. CONCLUSIONS: Scleroderma interstitial lung disease is characterised by
      a VEGF deficiency. Lower concentrations were found in patients with progression
      of lung disease.

PMID- 22402141
TI  - Positive association between STAT4 polymorphisms and polymyositis/dermatomyositis
      in a Japanese population.
AB  - OBJECTIVES: To investigate associations between signal transducer and activator
      of transcription 4 (STAT4), one of the most commonly acknowledged genes for the
      risk of multiple autoimmune diseases, with susceptibility to adult-onset
      polymyositis/dermatomyositis among Japanese individuals. METHODS: A single
      nucleotide polymorphism of STAT4, rs7574865, was genotyped using TaqMan assay in
      1143 Japanese individuals. The first set comprised 138
      polymyositis/dermatomyositis patients and 289 controls and the second set
      comprised 322 patients and 394 controls. 460 patients (273 polymyositis and 187
      dermatomyositis patients) and 683 controls were genotyped. RESULTS: rs7574865T
      conferred a risk of polymyositis/dermatomyositis with an OR of 1.37 (95% CI 1.16
      to 1.64; p=4x10(-4); p(corr)=0.0012). Both polymyositis and dermatomyositis
      exhibited high associations with the rs7574865T allele (polymyositis: OR=1.36,
      95% CI 1.11 to 1.67; p=0.0039; p(corr)=0.012; dermatomyositis: OR=1.40, 95% CI
      1.10 to 1.78; p=0.0054; p(corr)=0.016). The association between this STAT4
      polymorphism and interstitial lung disease (ILD) was also investigated in the
      first set of polymyositis/dermatomyositis patients (n=138); those with ILD (n=79)
      bore rs7574865T more frequently compared with controls (OR 1.59, 95% CI 1.10 to
      2.28; p=0.013; p(corr)=0.039). CONCLUSION: This is the first study to show a
      positive association between a STAT4 polymorphism and
      polymyositis/dermatomyositis, suggesting that polymyositis/dermatomyositis shares
      a gene commonly associated with the risk of other autoimmune diseases.

PMID- 22402142
TI  - Combination etanercept and methotrexate provides better disease control in very
      early (<=4 months) versus early rheumatoid arthritis (>4 months and <2 years):
      post hoc analyses from the COMET study.
AB  - OBJECTIVE: The objective of this post hoc analysis was to test the benefits of
      treating very early rheumatoid arthritis (VERA; <=4 months) using COMET trial
      data. Treatment response in VERA and early rheumatoid arthritis (ERA; >4 months
      to 2 years) with combination etanercept+methotrexate (ETN+MTX) or MTX monotherapy
      was compared. METHODS: Data assessed at week 52 for baseline disease duration
      effect included remission (disease activity score (DAS)28 <2.6, SDAI <=3.3,
      Boolean), low disease activity (LDA; DAS28 <3.2), Boolean components of remission
      and radiographic non-progression. Subjects who discontinued because of lack of
      efficacy were included as non-responders. RESULTS: Higher proportions of VERA
      subjects achieved LDA (79%) and DAS28 remission (70%) than ERA (62%, 48%,
      respectively, p<0.05) with ETN+MTX. Such high responses with MTX monotherapy were
      not observed (VERA, LDA=47%, DAS28 remission=35%; ERA, 47% and 32% respectively,
      p>0.70 for each). Regardless of disease duration, no radiographic progression was
      seen in 80% of subjects with ETN+MTX. In contrast, a higher proportion of VERA
      subjects showed no radiographic progression compared with ERA subjects treated
      with MTX (73.9% vs 50%, p=0.01). CONCLUSIONS: Treatment of VERA with ETN+MTX
      provides qualitatively improved clinical outcomes not seen with MTX monotherapy,
      supporting the pivotal role of TNF inhibition in early disease.

PMID- 22402143
TI  - Treatment with etanercept of autoimmune hepatitis associated with rheumatoid
      arthritis: an open label proof of concept study.

PMID- 22402144
TI  - Initiation and adherence to secondary prevention pharmacotherapy after myocardial
      infarction in patients with rheumatoid arthritis: a nationwide cohort study.
AB  - OBJECTIVES: To examine whether rheumatoid arthritis (RA) is associated with less
      optimal secondary prevention pharmacotherapy after first-time myocardial
      infarction (MI). METHODS: The authors identified all patients with first-time MI
      in the Danish National Patient Register from 2002 to 2009 and gathered individual
      level information including pharmacy records from nationwide registers.
      Initiation of standard care post-MI secondary prevention drugs, that is, aspirin,
      beta-blockers, clopidogrel, renin angiotensin system (RAS) blockers and statins,
      was determined after discharge. In addition, adherence to each drug was evaluated
      as the proportion of patients on treatment during follow-up and time to first
      treatment gap. RESULTS: A total of 66 107 MI patients (37% women) were discharged
      alive; 877 were identified as RA patients (59% women). Thirty days after
      discharge, RA was associated with significantly lower initiation of aspirin (OR
      0.80 (0.67-0.96)), beta-blockers (0.77 (0.65-0.92)) and statins (0.69 (0.58
      0.82)), while initiation of RAS blockers (0.80 (0.57-1.11)) and clopidogrel (0.88
      (0.75-1.02)) was non-significantly reduced. These estimates were virtually
      unchanged at day 180 and the results were corroborated by Cox regression
      analyses. Adherence to statins was lower in RA patients relative to non-RA
      patients (HR for treatment gap of 90 days: 1.26 (1.07-1.48)), while no
      significant differences were found in adherence to the other drugs. CONCLUSIONS:
      In this nationwide study of unselected patients with first-time MI, a reduced
      initiation of secondary prevention pharmacotherapy was observed in RA patients.
      This undertreatment may contribute to the increased cardiovascular disease burden
      in RA and the underlying mechanisms warrant further study.

PMID- 22402145
TI  - Remission induction therapy with methotrexate and prednisone in patients with
      early rheumatoid and undifferentiated arthritis (the IMPROVED study).
AB  - AIM: Classifying more patients as rheumatoid arthritis (RA) (2010 American
      College of Rheumatology/European League Against Rheumatism criteria for RA) may
      improve treatment outcomes but may cause overtreatment in daily practice. The
      authors determined the efficacy of initial methotrexate (MTX) plus prednisone
      treatment in patients with 1987 or 2010 classified RA and undifferentiated
      arthritis (UA). METHOD: 610 recent onset RA or UA patients started with MTX 25
      mg/week and prednisone 60 mg/day tapered to 7.5 mg/day in 7 weeks. Percentage
      remissions after 4 months were compared between RA (1987 or 2010 criteria) and
      UA. Predictors for remission were identified. RESULTS: With the 2010 criteria,
      19% more patients were classified as RA than with the 1987 criteria, but similar
      remission rates were achieved: 291/479 (61%) 2010 classified RA and 211/264 (58%)
      1987 classified RA patients (p=0.52), and 79/122 (65%) UA patients (p=0.46).
      Anticitrullinated protein antibodies (ACPA) positive RA patients achieved more
      remission (66%) than ACPA negative RA patients (51%, p=0.001), but also had a
      lower mean baseline Disease Activity Score (DAS) (3.2 vs 3.6, p<0.001).
      Independent predictors for remission were male sex, low joint counts, DAS and
      Health Assessment Questionnaire, low body mass index and ACPA positivity.
      CONCLUSION: Initial treatment with MTX and a tapered high dose of prednisone
      results in similarly high remission percentages after 4 months (about 60%) in RA
      patients, regardless of fulfilling the 1987 or 2010 criteria, and in UA patients.
      Independent predictors indicate that initiating treatment while disease activity
      is relatively low results in more remission.

PMID- 22402146
TI  - Do worsening scleroderma capillaroscopic patterns predict future severe organ
      involvement? a pilot study.
AB  - OBJECTIVE: Assessment of associations of nailfold videocapillaroscopy (NVC)
      scleroderma patterns ('early', 'active' and 'late') with future severe clinical
      involvement in a systemic sclerosis (SSc) population. METHODS: Sixty-six
      consecutive patients with SSc according to the LeRoy and Medsger criteria
      underwent NVC assessment at baseline. Videocapillaroscopic images were classified
      into 'normal', 'early', 'active' or 'late' NVC pattern. Clinical evaluation was
      performed for nine organ systems (general, peripheral vascular, skin, joint,
      muscle, gastrointestinal tract, lung, heart and kidney) according to the disease
      severity scale of Medsger (DSS) at 18-24 months of follow-up. Severe clinical
      involvement was defined as category 2-4 per organ of the DSS. RESULTS: NVC
      patterns were significantly associated with future severe, peripheral
      vascular/lung involvement at 18-24 months. The OR rose steadily throughout the
      patterns. The OR for future severe peripheral disease based on simple/multiple
      (correcting for disease duration, subset and medication) logistic regression was
      2.49/2.52 (95% CI 1.33 to 5.43, p=0.003/1.11 to 7.07, p=0.026) for early,
      6.18/6.37 for active and 15.35/16.07 for late NVC scleroderma patterns versus the
      normal NVC pattern. The OR for future severe lung involvement based on
      simple/multiple regression was 2.54/2.33 (95% CI 1.40 to 5.22, p=0.001/1.13 to
      5.52, p=0.021) for early, 6.43/5.44 for active and 16.30/12.68 for late NVC
      patterns. CONCLUSIONS: This pilot study is the first demonstrating an association
      between baseline NVC patterns and future severe, peripheral vascular and lung
      involvement with stronger odds according to worsening scleroderma patterns. This
      may indicate a putative role of capillaroscopy as a biomarker.

PMID- 22402147
TI  - Evidence for caveolin-1 as a new susceptibility gene regulating tissue fibrosis
      in systemic sclerosis.
AB  - OBJECTIVE: Caveolin-1 (CAV1) is an inhibitor of tissue fibrosis and has been
      implicated in the pathogenesis of systemic sclerosis (SSc). The aim of the study
      was to analyse the possible association of CAV1 gene single nucleotide
      polymorphisms (SNP) with SSc. METHODS: A total population of 3974 individuals
      (1355 SSc patients, 2619 controls) was studied. Genotype data for 23 SNP spanning
      the CAV1-CAV2 gene locus were obtained from a genome-wide scan conducted in a
      French population (564 SSc patients, 1776 controls). Three CAV1 SNP (rs926198,
      rs959173, rs9920) displaying the most significant associations with SSc and/or
      clinical phenotypes were then genotyped in an Italian population (791 SSc
      patients, 843 controls). CAV1 protein expression in skin biopsies was
      investigated by immunohistochemistry and western blotting. RESULTS: In the French
      population, the CAV1 rs959173 C minor allele showed a significant protective
      association with susceptibility to SSc (OR 0.71, 95% CI 0.59 to 0.86,
      p(adjusted)=0.009), and with the subset of patients with limited cutaneous SSc
      (OR 0.71, 95% CI 0.56 to 0.89, p(adjusted)=0.018). The association was replicated
      in the Italian population and strengthened in the combined populations through
      Cochran-Mantel-Haenszel meta-analysis (SSc: pooled OR 0.81, 95% CI 0.71 to 0.92,
      p=0.0018; limited cutaneous SSc: pooled OR 0.80, 95% CI 0.69 to 0.93, p=0.0053).
      Genotype/protein expression correlations revealed that the rs959173 C protective
      allele was associated with increased CAV1 protein expression. CONCLUSIONS: These
      results add CAV1 to the list of SSc susceptibility genes and provide further
      evidence for the contribution of this pathway in the fibrotic process that
      characterises SSc pathogenesis.

PMID- 22402149
TI  - The microstructure and properties of cyclic extrusion compression treated Mg-Zn-Y
      Nd alloy for vascular stent application.
AB  - Magnesium alloys are promising candidate materials for cardiovascular stents due
      to their good biocompatibility and degradation properties in the human body.
      However, in vivo tests also show that improvement in their mechanical properties
      and corrosion resistance is necessary before wide application. In this study,
      cyclic extrusion compression (CEC) was used to enhance the mechanical properties
      and corrosion resistance of Mg-Zn-Y-Nd alloy. The results show that the grain
      size was greatly refined to 1 MUm after CEC treatment. The second phase
      distributed along the grain boundaries with grid shape and nano-sized particles
      uniformly distributed in grains. The elongation (delta), ultimate tensile
      strength (UTS) and yield strength (YS) of the CEC treatment samples were 30.2%,
      303 MPa and 185 MPa respectively. The CEC treated samples showed homogeneous
      corrosion because of the grain refinement and the homogeneous distribution of
      nano-sized second phase. The corrosion current density of the alloy decreased
      from 2.8*10(-4) A/cm(2) to 6.6*10(-5) A/cm(2) after CEC treatment. Therefore,
      improved mechanical properties, uniform corrosion and reduced corrosion rate
      could be achieved by CEC.

PMID- 22402150
TI  - Experimental study on dieless drawing of Nickel-Titanium alloy.
AB  - The effect of a dieless drawing process on commercial grade Nickel-Titanium rods,
      of 5 mm diameter, was investigated by varying the established critical process
      parameters of temperature, cooling rate, drawing velocity, and heating/cooling
      velocity. The rods were successfully dieless drawn with a maximum steady state
      reduction in cross-sectional area of 54%. The thermal and mechanical loading
      profiles of the rod during processing, and the resulting changes in
      microstructure and hardness, have been investigated. Uniform levels of stress and
      strain resulted in uniform reduction of the rod cross-sectional area. The grain
      structure was highly deformed in the drawing direction and increased porosity was
      observed as a result of the process. The longitudinal section hardness of the rod
      was significantly reduced as a result of the dieless drawing process. Any
      failures that arose were due to discontinuities within the material
      microstructure caused by a high necking rate, shorter exposure time to the
      process temperature and low heating and cooling rates. A uniform oxidation layer
      was observed on the surface of the processed rods as a result of processing in
      atmospheric conditions. This oxidation layer has the potential to aid in the
      lubrication of subsequent cold working operations of the dieless drawn rods.
      Coupling the thermomechanical effects of the dieless drawing process with a cold
      drawing processing step has the potential to produce a NiTi wire in fewer passes,
      and therefore at a reduced cost.

PMID- 22402151
TI  - Part I: porosity dependence of the Weibull modulus for hydroxyapatite and other
      brittle materials.
AB  - Porous brittle materials are used as filters, catalyst supports, solid oxide fuel
      cells and biomedical materials. However the literature on the Weibull modulus, m,
      versus volume fraction porosity, P, is extremely limited despite the importance
      of m as a gauge of mechanical reliability. In Part I of this study, m is
      determined for 441 sintered hydroxyapatite (HA) specimens fractured in biaxial
      flexure for 0.08 <= P <= 0.62. In this study, we analyze a combined data set
      collected from the literature that represents work from a total of 17 different
      research groups (including the present authors), eight different materials and
      more than 1560 oxide and non-oxide specimens, the m versus P plot is "U-shaped"
      with a wide band of m values for P<0.1 (Region I) and P>0.55 (Region III), and a
      narrower band of m values in the intermediate porosity region of 0.1<P<0.55
      (Region II). The limited range of m (~4<m<11) in Region II has important
      implications since Region II includes the P range for the majority of the
      applications of porous brittle materials. Part II of this study focuses on the P
      dependence of the mean fracture strength,<sigma(f)>, and the Young's modulus E
      for the HA specimens tested in Part I along with literature data for other
      brittle materials. Both <sigma(f)> and E are power law functions of the degree of
      densification, phi, where phi=1-P/P(G) and P(G) is the green (unfired) porosity.

PMID- 22402152
TI  - Role of tooth elongation in promoting fracture resistance.
AB  - A study is made of the role of tooth height on the resistance to side-wall
      longitudinal fracture under axial occlusal loading, building on earlier analyses
      for molar teeth with low dome-like ('bunodont') crown structures characteristic
      of primates and several other omnivorous mammals. The present study extends the
      analysis by considering molar teeth with an elongate columnar structure below the
      crown, more characteristic of grazing mammals. Extended finite element modeling
      is used to determine the evolution of longitudinal cracking, from initial growth
      to final failure. Experimental tests on sheep teeth confirm the predicted
      behavior of the longitudinal fracture mode, at least in its early stages. It is
      demonstrated that elongate tooth structures have a substantially increased
      resistance to longitudinal fracture, by restricting crack growth along the
      extended side walls. Biological implications concerning the adaptation of tooth
      structure to meet changes in the dietary habits of herbivores, and of some
      carnivores, are considered.

PMID- 22402153
TI  - Ceramic-like wear behaviour of human dental enamel.
AB  - This paper reports a transmission electron microscopy (TEM) analysis of
      subsurfaces of enamel specimens following in vitro reciprocating wear tests with
      an enamel cusp sliding on a flat enamel specimen under hydrated conditions. The
      obtained results show that crack formation occurred in the wear scar subsurface.
      The path followed by these cracks seems to be dictated either by the histological
      structure of enamel or by the contact stress field. Moreover, the analysis of a
      set of enamel wear results obtained from the literature and application of
      fracture-based models, originally developed for ceramics, correlate well,
      confirming the similar wear processes taking place in these materials. This
      analysis also reveals a marked influence of coefficient of friction on the enamel
      wear rate: for a higher coefficient of friction value, enamel wear can be severe
      even under forces generated during normal operation of teeth.

PMID- 22402154
TI  - Mechanical characterization of a customized decellularized scaffold for vascular
      tissue engineering.
AB  - Several challenges persist when attempting to utilize decellularized tissue as a
      scaffold for vascular tissue engineering. Namely: poor cell
      infiltration/migration, excessive culture times associated with repopulating the
      scaffolds, and the achievement of a quiescent medial layer. In an attempt to
      create an optimum vascular scaffold, we customized the properties of
      decellularized porcine carotid arteries by: (i) creating cavities within the
      medial layer to allow direct injection of cells, and (ii) controlling the amount
      of collagen digestion to increase the porosity. Histological examination of our
      customized scaffold revealed a highly porous tissue structure containing
      consistent medial cavities running longitudinally through the porous scaffold
      wall. Mechanical testing of the customized scaffold showed that our minimal
      localized disruption to the ECM does not have a detrimental effect on the bulk
      mechanical response of the tissue. The results demonstrate that an increased
      stiffness and reduced distensibility occurs after decellularization when compared
      to the native tissue, however post scaffold customization we can revert the
      scaffold tensile properties back to that of the native tissue. This most
      noteworthy result occurs in the elastin dominant phase of the tensile response of
      the scaffold, indicating that no disruption has occurred to the elastin network
      by our decellularization and customization techniques. Additionally, the bulk
      seeding potential of the customized scaffold was demonstrated by direct injection
      of human smooth muscle cells through the medial cavities. The optimum cell
      dispersion was observed in the highest porosity scaffold, with large cell numbers
      retained within the medial layer after 24 h static culture. In summary, this
      study presents a novel customized decellularized vascular scaffold that has the
      capability of bulk seeding the media, and in tandem to this method, the porosity
      of the scaffold has been increased without compromising the mechanical integrity.

PMID- 22402155
TI  - What is the role of lipopolysaccharide on the tribocorrosive behavior of
      titanium?
AB  - In an oral environment, titanium dental implants are exposed to a complex
      degradation process which is predominantly influenced by the intermittent
      mechanical events (mastication), continuous exposure to varying chemical
      solutions (saliva and food) and formation of microbiological (biofilm). Several
      studies have investigated the chemical corrosion and mechanical resistance of
      titanium; however, very few attempted to report on the effects of combined
      chemical, mechanical and microbiological interactions, which simulates the oral
      environment. A new multi-disciplinary research area, "tribocorrosion" (a combined
      study of wear and corrosion), was used to address such issues. The tribocorrosive
      nature of titanium in artificial saliva (pH 6.5) with lipopolysaccharide (LPS)
      was investigated. Twenty-four titanium discs (12 mm diameter, 7 mm thickness),
      were divided into 8 groups (n=3) as a function of material (commercially pure
      titanium (cpTi) and titanium-aluminum-vanadium (TiAlV) alloy) and LPS
      concentrations (0, 0.15, 15 and 150 MUg/ml). Sliding duration (2000 cycles),
      frequency (1.2 Hz) and load (20 N) parameters mimicked the daily mastication
      process. Electrochemical impedance spectroscopy was conducted before and after
      tribocorrosion to comprehend the changes in corrosion kinetics. Worn surfaces
      were examined using white-light-interferometry and scanning electron microscopy.
      Total weight loss and roughness values were calculated. LPS affected the
      tribocorrosive behavior of both titanium types. LPS statistically accelerated the
      ion exchange between titanium and saliva, and reduced the resistance of the
      titanium surface against corrosion (p<.05). Sliding events decreased the
      protectiveness of the titanium surface. In general, TiAlV exhibited better
      corrosion behavior, but both titanium types showed similar in total weight loss
      (p>.05). LPS significantly increased the cpTi weight loss (p=.041), and the
      roughness of the surface (p<.001). In summary, LPS negatively affected the
      corrosion/wear behavior of titanium, which may contribute to the failure of
      dental implants.

PMID- 22402156
TI  - Porous alumina-hydroxyapatite composites through protein foaming-consolidation
      method.
AB  - This report presents physical characterization and cell culture test of porous
      alumina-hydroxyapatite (HA) composites fabricated through protein foaming
      consolidation technique. Alumina and HA powders were mixed with yolk and starch
      at an adjusted ratio to make slurry. The resulting slip was poured into
      cylindrical shaped molds and followed by foaming and consolidation via 180 
      degrees C drying for 1 h. The obtained green bodies were burned at 600  degrees C
      for 1 h, followed by sintering at temperatures of 1200-1550  degrees C for 2 h.
      Porous alumina-HA bodies with 26-77 vol.% shrinkage, 46%-52% porosity and 0.1-6.4
      MPa compressive strength were obtained. The compressive strength of bodies
      increased with the increasing sintering temperatures. The addition of commercial
      HA in the body was found to increase the compressive strength, whereas the case
      is reverse for sol-gel derived HA. Biocompatibility study of porous alumina-HA
      was performed in a stirred tank bioreactor using culture of Vero cells. A good
      compatibility of the cells to the porous microcarriers was observed as the cells
      attached and grew at the surface of microcarriers at 8-120 cultured hours. The
      cell growth on porous alumina microcarrier was 0.015 h(-1) and increased to 0.019
      h(-1) for 0.3 w/w HA-to-alumina mass ratio and decreased again to 0.017 h(-1) for
      1.0 w/w ratio.

PMID- 22402157
TI  - Part II: fracture strength and elastic modulus as a function of porosity for
      hydroxyapatite and other brittle materials.
AB  - Part I of this paper discussed the Weibull modulus m, versus porosity P behavior
      of brittle materials, including HA. While the Weibull modulus m deals with the
      scatter in fracture strength data, this paper (Part II) focuses on two additional
      key mechanical properties of porous materials, namely the average fracture
      strength <sigma(f)>, and Young's modulus E, for P in the interval from P~ zero to
      P~P(G) (the porosity of the unfired compacts). The <sigma(f)> versus P data for
      HA from this study and the literature data for alumina, yttria stabilized
      zirconia (YSZ) and silicon nitride are described well by functions of phi, where
      phi=1-P/P(G)= the degree of densification. A similar function of phi applies to
      the <E> versus P behavior of HA from this study and data from the literature for
      alumina, titanium and YSZ. All of the data analyzed in this study (Part II) are
      based on partially and fully sintered powder compacts (excluding green powder
      compacts), thus the <sigma(f)>/sigma(0) versus phi and <E>/E(0) versus phi
      relationships may apply only to such specimens.

PMID- 22402158
TI  - Mechanical characterization and constitutive modelling of the damage process in
      rectus sheath.
AB  - The aim of this study is to characterize and model the damage process in the
      anterior rectus abdominal aponeurosis (anterior rectus sheath) undergoing finite
      deformations. The resistance of the anterolateral abdominal aponeuroses is
      important when planning the surgical repair of incisional hernias, among other
      medical procedures. Previous experiments in prolapsed vaginal tissue revealed
      that a softening process occurs before tissue rupture. This nonlinear damage
      behaviour requires a continuum damage theory commonly used to describe the
      softening behaviour of soft tissues under large deformations. The structural
      model presented here was built within the framework of non-linear continuum
      mechanics. Tissue damage was simulated considering different damage behaviours
      for the matrix and the collagen fibres. The model parameters were fit to the
      experimental data obtained from anterior rectus sheath samples undergoing finite
      deformations in uniaxial tension tests. The tests were carried out with samples
      cut along the direction of the collagen fibres, and transversal to the fibres.
      Longitudinal and transverse mechanical properties of human anterior rectus sheath
      are significantly different. The damage model was able to predict the stress
      strain behaviour and the damage process accurately. The error estimations pointed
      to an excellent agreement between experimental results and model fittings. For
      all the fitted data, the normalized RMS error epsilon presented very low values
      and the coefficient of determination R(2) was close to 1. The present work
      constitutes the first attempt (as far as the authors know) to present a damage
      model for the human rectus sheath.

PMID- 22402159
TI  - Acoustic emission and fatigue damage induced in plasma-sprayed hydroxyapatite
      coating layers.
AB  - In order to improve the adhesive strength of hydroxyapatite (HAp) coatings, grit
      blasting with Al(2)O(3) powder and then wet blasting with HAp/Ti mixed powders
      was carried out on a commercially pure Ti (cp-Ti) substrate. Subsequently, an
      HAp/Ti bond coat layer and HAp top coat layer were deposited by plasma spraying.
      Fatigue tests of the HAp-coated specimens were carried out under four-point
      bending. Acoustic emission (AE) signals during the entire fatigue test were
      monitored to investigate the fatigue cracking behavior of the HAp-coated
      specimens. The HAp-coated specimens could survive up to 10(7) cycles without
      spallation of the HAp coating layers at the stress amplitude of 120 MPa. The HAp
      coated specimens without HAp/Ti bond coat layer showed shorter fatigue life and
      easy crack nucleation compared to the HAp-coated specimens with HAp/Ti bond coat
      layer. The delamination and spallation of the HAp top coat with HAp/Ti bond coat
      on cp-Ti was not observed until the crack propagated into the cp-Ti during the
      final fracture stage of the fatigue cycle. Therefore, the HAp/Ti bond coat layer
      was found to greatly improve the fatigue damage resistance of the HAp coating
      layer. Three stages of the fatigue failure behavior of the HAp top coat with
      HAp/Ti bond coat on a cp-Ti substrate can be clearly estimated by the AE
      monitoring technique. These stages are cracks nucleating and propagating in the
      coating layer, cracks propagating in the substrate, and cracks propagating
      unstably to final fracture.

PMID- 22402160
TI  - Reliable measurement of elastic modulus of cells by nanoindentation in an atomic
      force microscope.
AB  - The elastic modulus of an oral cancer cell line UM1 is investigated by
      nanoindentation in an atomic force microscope with a flat-ended tip. The commonly
      used Hertzian method gives apparent elastic modulus which increases with the
      loading rate, indicating strong effects of viscoelasticity. On the contrary, a
      rate-jump method developed for viscoelastic materials gives elastic modulus
      values which are independent of the rate-jump magnitude. The results show that
      the rate-jump method can be used as a standard protocol for measuring elastic
      stiffness of living cells, since the measured values are intrinsic properties of
      the cells.

PMID- 22402161
TI  - Hyperelastic mechanical behavior of chitosan hydrogels for nucleus pulposus
      replacement-experimental testing and constitutive modeling.
AB  - Chitosan hydrogels (CHs) have been considered as a potential implant material for
      replacement and repair of the Nucleus Pulposus (NP) within the intervertebral
      disk. The nonlinear mechanical behavior of a CH material is investigated
      experimentally and computationally in this study. A series of confined and
      unconfined compression tests are designed and conducted for this hydrogel.
      Hyperelastic strain energy density functions (SEDFs) are calibrated using the
      experimental data. A hyperelastic constitutive model is selected to best fit the
      multi-axial behavior of the hydrogel. Its general prediction ability is verified
      using finite element (FE) simulations of hydrogel indentation experiments
      conducted using a spherical tip indentor. In addition, digital image correlation
      (DIC) technique is also used in the indentation test in order to process the full
      field surface strains where the indentor contacts the hydrogel. The DIC test
      results in the form of top-surface strains compared well with those predicted by
      the FE model. Results show repeatability for the examined specimens under the
      applied tests. Confined and unconfined test results are found to be sufficient to
      calibrate the SEDFs. The Ogden model was selected to represent the nonlinear
      behavior of the CH material which can be used in future biomechanical simulations
      of the spine.

PMID- 22402162
TI  - Phase stability, mechanical property, and electronic structure of an Mg-Ca
      system.
AB  - First principle calculations reveal that Mg-Ca phases are energetically favorable
      with negative heats of formation within the entire composition range, and that a
      strong chemical bonding is formed between Mg and Ca atoms. Calculations also show
      that the composition has an important effect on mechanical properties of Mg-Ca,
      and that the Mg-Ca phases with an Mg composition of less than 50 at.% would be
      good candidates as degradable bone materials in terms of Young's modulus and
      ductility. In addition, it is found out that Mg(3)Ca, MgCa and MgCa(3) have phase
      sequences of BCC->HCP, BCC->HCP and FCC->HCP under high pressure, respectively,
      and that Ca plays a dominant role in determining the electronic structures and
      stable crystal structures of various Mg-Ca phases.

PMID- 22402163
TI  - Kinematics of cardiac growth: in vivo characterization of growth tensors and
      strains.
AB  - Progressive growth and remodeling of the left ventricle are part of the natural
      history of chronic heart failure and strong clinical indicators for survival.
      Accompanied by changes in cardiac form and function, they manifest themselves in
      alterations of cardiac strains, fiber stretches, and muscle volume. Recent
      attempts to shed light on the mechanistic origin of heart failure utilize
      continuum theories of growth to predict the maladaptation of the heart in
      response to pressure or volume overload. However, despite a general consensus on
      the representation of growth through a second order tensor, the precise format of
      this growth tensor remains unknown. Here we show that infarct-induced cardiac
      dilation is associated with a chronic longitudinal growth, accompanied by a
      chronic thinning of the ventricular wall. In controlled in vivo experiments
      throughout a period of seven weeks, we found that the lateral left ventricular
      wall adjacent to the infarct grows longitudinally by more than 10%, thins by more
      than 25%, lengthens in fiber direction by more than 5%, and decreases its volume
      by more than 15%. Our results illustrate how a local loss of blood supply induces
      chronic alterations in structure and function in adjacent regions of the
      ventricular wall. We anticipate our findings to be the starting point for a
      series of in vivo studies to calibrate and validate constitutive models for
      cardiac growth. Ultimately, these models could be useful to guide the design of
      novel therapies, which allow us to control the progression of heart failure.

PMID- 22402164
TI  - Microstructure and antibacterial property of in situ TiO(2) nanotube
      layers/titanium biocomposites.
AB  - The TiO(2) nanotube layer was in situ synthesized on the surface of pure titanium
      by the electrochemical anodic oxidation. The diameter of nano- TiO(2) nanotubes
      was about 70~100 nm. The surface morphology and phase compositions of TiO(2)
      nanotube layers were observed and analyzed using the scanning electron microscope
      (SEM). The important processing parameters, including anodizing voltage, reaction
      time, concentration of electrolyte, were optimized in more detail. The
      photocatalytic activity of the nano- TiO(2) nanotube layers prepared with optimal
      conditions was evaluated via the photodegradation of methylthionine in aqueous
      solution. The antibacterial property of TiO(2) nanotube layers prepared with
      optimal conditions was evaluated by inoculating Streptococcus mutans on the
      TiO(2) nanotube layers in vitro. The results showed that TiO(2) nanotube
      layers/Ti biocomposites had very good antibacterial activity to resist
      Streptococcus mutans. As a dental implant biomaterial, in situ TiO(2) nanotube
      layer/Ti biocomposite has better and wider application prospects.

PMID- 22402165
TI  - Deformable image registration and 3D strain mapping for the quantitative
      assessment of cortical bone microdamage.
AB  - The resistance to forming microcracks is a key factor for bone to withstand
      critical loads without fracturing. In this study, we investigated the initiation
      and propagation of microcracks in murine cortical bone by combining three
      dimensional images from synchrotron radiation-based computed tomography and time
      lapsed biomechanical testing to observe microdamage accumulation over time.
      Furthermore, a novel deformable image registration procedure utilizing digital
      volume correlation and demons image registration was introduced to compute 3D
      strain maps allowing characterization of the mechanical environment of the
      microcracks. The displacement and strain maps were validated in a priori tests.
      At an image resolution of 740 nm the spatial resolution of the strain maps was 10
      MUm (MTF), while the errors of the displacements and strains were 130 nm and
      0.013, respectively. The strain maps revealed a complex interaction of the
      propagating microcracks with the bone microstructure. In particular, we could
      show that osteocyte lacunae play a dual role as stress concentrating features
      reducing bone strength, while at the same time contributing to the bone toughness
      by blunting the crack tip. We conclude that time-lapsed biomechanical imaging in
      combination with three-dimensional strain mapping is suitable for the
      investigation of crack initiation and propagation in many porous materials under
      various loading scenarios.

PMID- 22402166
TI  - Mode III cleavage of a coin-shaped titanium implant in bone: effect of friction
      and crack propagation.
AB  - Endosseous cementless implants are widely used in orthopaedic, maxillofacial and
      oral surgery. However, failures are still observed and remain difficult to
      anticipate as remodelling phenomena at the bone-implant interface are poorly
      understood. The assessment of the biomechanical strength of the bone-implant
      interface may improve the understanding of the osseointegration process. An
      experimental approach based on a mode III cleavage mechanical device aims at
      understanding the behaviour of a planar bone-implant interface submitted to
      torsional loading. To do so, coin-shaped titanium implants were inserted on the
      tibiae of a New Zealand white rabbit for seven weeks. After the sacrifice, mode
      III cleavage experiments were performed on bone samples. An analytical model was
      developed to understand the debonding process of the bone-implant interface. The
      model allowed to assess the values of different parameters related to bone tissue
      at the vicinity of the implant with the additional assumption that bone adhesion
      occurs over around 70% of the implant surface, which is confirmed by microscopy
      images. The approach allows to estimate different quantities related to the bone
      implant interface such as: torsional stiffness (around 20.5 N m rad(-1)), shear
      modulus (around 240 MPa), maximal torsional loading (around 0.056 N.m), mode III
      fracture energy (around 77.5 N m(-1)) and stress intensity factor (0.27 MPa
      m(1/2)). This study paves the way for the use of mode III cleavage testing for
      the investigation of torsional loading strength of the bone-implant interface,
      which might help for the development and optimization of implant biomaterial,
      surface treatment and medical treatment investigations.

PMID- 22402167
TI  - Fabrication and characterization of poly(L-lactide-co-glycolide) knitted mesh
      reinforced collagen-chitosan hybrid scaffolds for dermal tissue engineering.
AB  - Mechanical properties are essential considerations for the design of porous
      scaffolds in the field of tissue engineering. To develop a well-supported hybrid
      dermal substitute, poly(L-lactide-co-glycolide) (PLGA) yarns were knitted into a
      mesh with relative fixed loops, followed by incorporation into collagen-chitosan
      scaffolds (CCS) to obtain PLGA knitted mesh-reinforced CCS (PLGAm/CCS). The
      morphology and tensile strength in both the dry and wet state of PLGAm/CCS were
      investigated in vitro. To characterize the tissue response, specifically
      angiogenesis and tissue regeneration, PLGAm/CCS was embedded subcutaneously in
      Sprague-Dawley rats and compared with two control implants, i.e., PLGA mesh
      (PLGAm) and CCS. At weeks 1, 2, and 4 post surgery, tissue specimens were
      harvested for histology, immunohistochemistry, real-time quantitative PCR and
      Western blot analysis. These results demonstrated that the incorporation of PLGA
      knitted mesh into CCS can improve the mechanical strength with little influence
      on its mean pore size and porosity. After implantation, PLGAm/CCS can resist
      contraction and promote cell infiltration, neotissue formation, and blood vessel
      ingrowth, effectively. In conclusion, the mechanical strength of scaffolds can
      play a synergetic role in tissue regeneration and vascularization by maintaining
      its 3D microstructure. The ability of PLGAm/CCS to promote angiogenesis and
      induce in situ tissue formation demonstrates its strong potential in the field of
      skin tissue engineering.

PMID- 22402168
TI  - Effects of temperature and photoperiod on termination of pseudopupal diapause in
      the bean blister beetle, Epicauta gorhami.
AB  - Larvae of the bean blister beetle, Epicauta gorhami (Coleoptera: Meloidae), feed
      on grasshopper eggs in soil and undergo hypermetamorphosis. This beetle undergoes
      larval diapause in the fifth instar as a pseudopupa, a form characteristic of
      hypermetamorphosis in meloid beetles. This pseudopupal diapause is maintained for
      a long period if the larvae are kept under continuous diapause-inducing short-day
      conditions. In the present study, the effects of temperature and photoperiod on
      termination of pseudopupal diapause in E. gorhami were examined using pseudopupae
      obtained under 12L-12D at 25 degrees C. Diapause was terminated by exposure to
      low or high temperature, but not by transfer to long-day conditions. The
      pseudopupal stage comprises diapause and post-diapause phases despite its
      unchanging appearance. The optimum low temperature for diapause termination was
      10-15 degrees C, and a higher or lower temperature was less effective. There was
      an individual variation in the low temperature requirement for diapause
      termination and post-diapause development may not occur until this requirement is
      satisfied. Although under natural conditions pseudopupae may encounter low
      temperatures that are effective for diapause termination at different ages, our
      results show that pseudopupae at various ages respond similarly to low
      temperature exposure. This response may ensure that resumption of development
      synchronizes in a population.

PMID- 22402169
TI  - Identification of nuclear receptors involved in regulation of male reproduction
      in the red flour beetle, Tribolium castaneum.
AB  - Nineteen canonical and two Knirps-like family nuclear receptors (NRs) were
      identified in the genome of Tribolium castaneum. The current study was conducted
      to identify NRs involved in regulation of male reproduction. RNA interference
      (RNAi)-aided knockdown in the expression of genes coding for all 21 NRs showed
      that reduction in the levels of 11 NRs (E75, E78, FTZ-F1, HR38, HR4, Knirps-like,
      HNF4, Tailless, HR51, Dsf and HR39) in the male beetles caused more than 50%
      reduction in the eggs laid by the female beetles mated with RNAi male beetles.
      Among these 11 NRs that are required for male reproduction, knockdown in the
      expression of genes coding for E78 and HR39 in the male beetles resulted in a
      reduction in the number of sperm produced and transferred to the female when
      compared to the sperms produced and transferred by the control male beetles
      injected with bacterial malE dsRNA. In contrast, knockdown in the expression of
      genes coding for E75 and HR38 caused a reduction in the size of male accessory
      glands (MAG), the amount of protein produced by the MAG and the expression of
      genes coding for accessory gland proteins. These data suggest that NRs such as
      E78 and HR39 regulate sperm production and their transfer to the females and the
      other NRs such as E75 and HR38 regulate the development of MAG and the production
      of accessory gland proteins.

PMID- 22402170
TI  - A new rapid method for Clostridium difficile DNA extraction and detection in
      stool: toward point-of-care diagnostic testing.
AB  - We describe a new method for the rapid diagnosis of Clostridium difficile
      infection, with stool sample preparation and DNA extraction by heat and physical
      disruption in a single-use lysis microreactor (LMR), followed by a rapid PCR
      amplification step. All steps can be accomplished in <20 minutes overall. Gel
      electrophoresis is currently used to detect the amplification product, pending
      real-time availability with an ultra-rapid thermocycler. Compared with the dual
      enzyme immunoassay (EIA) screening test (C. diff Quik Chek Complete; Techlab,
      Blacksburg, VA), the novel LMR/PCR assay showed complete concordance with all
      glutamate dehydrogenase (GDH) results (GDH(+)/toxin(+), n = 48; GDH(-)/toxin(-),
      n = 81). All 69 stool samples with discordant EIA results (GDH(+)/toxin(-)) were
      tested by both the LMR/PCR assay and the loop-mediated isothermal amplification
      test (LAMP) (Illumigene C. difficile; Meridian Bioscience, Cincinnati, OH). In
      64/69 EIA-discordant samples, LAMP and LMR/PCR results matched (both positive in
      29 sample and both negative in 35 samples); in the remaining 5 samples, results
      were discrepant between the LAMP assay (all five negative) and the LMR/PCR assay
      (all 5 positive). Overall, LMR/PCR testing matched the current algorithm of EIA
      and/or LAMP reflex testing in 193/198 (97.5%) samples. The present proof-of
      concept study suggests that the novel LMR/PCR technique described here may be
      developed as an inexpensive, rapid, and reliable point-of-care diagnostic test
      for C. difficile infection and other infectious diseases.

PMID- 22402171
TI  - Nursing homes appeals of deficiencies: the informal dispute resolution process.
AB  - OBJECTIVE: Nursing homes that are not meeting quality standards are cited for
      deficiencies. Before 1995, the only recourse for a nursing home was a formal
      appeal process, which is lengthy and costly. In 1995, the Centers for Medicare &
      Medicaid Services instituted the Informal Dispute Resolution (IDR) process. This
      study presents for the first time national statistics about the IDR process and
      an analysis of the factors that influence nursing homes' decisions to request an
      IDR. DESIGN: Retrospective study including descriptive statistics and
      multivariate logistic hierarchical models. SETTING: US nursing homes from 2005 to
      2008. PARTICIPANTS: Participants were 15,916 Medicaid- and Medicare-certified
      nursing homes nationally, with 94,188 surveys and 9388 IDRs. MEASURES: The unit
      of observation was an annual survey or a complaint survey that generated at least
      one deficiency. The dependent variable was dichotomous and indicated whether the
      annual or a complaint survey triggered an IDR request. Independent variables
      included characteristics of the nursing home, the deficiency, the market, and the
      state regulatory environment. RESULTS: Ten percent of all annual surveys and
      complaint surveys resulted in IDRs. There was substantial variation across
      states, which persisted over time. Multivariate results suggest that nursing
      homes' decisions to request an IDR depend on their assessment of the probability
      of success and assessment of the benefits of the submission. CONCLUSIONS: Nursing
      homes avail themselves of the IDR process. Their propensity to do so depends on a
      number of factors, including the state regulatory system and the market
      environment in which they operate.

PMID- 22402172
TI  - Hematological and morphological investigation of thrombogenic mechanisms in the
      lungs of phenylhydrazine-treated rats.
AB  - Abnormality in hematological condition including hemolytic disorders has been
      suggested one of the risk factor of pulmonary thrombosis. We previously reported
      that phenylhydrazine (PHZ) could induce acute thrombosis in the rat lung. In this
      study, time-related hematological and histopathological changes were evaluated in
      PHZ-treated rats to reveal the pathogenesis of pulmonary thrombosis in hemolytic
      condition. Male Sprague-Dawley rats were administered PHZ at 40 mg/kg/day daily
      for up to 4 days (n=6). At 24 h after the last administration (i.e. on days 1, 2,
      3, or 4), animals were euthanized and samples were subjected to hematology, light
      microscopy, and electron microscopy. PHZ-treated rats developed severe anemia on
      day 1 or later. On day 2 and after, congestion in the alveolar septa
      corresponding to accumulation of deformed/ghost erythrocytes in the alveolar
      capillaries was observed, which was the earliest change that preceded thrombus
      formation. Focal fibrin deposition in the alveolar septa was noted on day 3 and
      it expanded widely by day 4, while endothelial injury were minimally noted just
      on day 4. These congestive/thrombotic changes were predominant in the pulmonary
      capillaries. Changes in hemostatic parameters were noted only on day 4; which
      were prolonged prothrombin time and activated partial thromboplastin time,
      greatly increased plasma thrombin-antithrombin complex levels with statistical
      significance, and slightly decreased fibrinogen levels. In conclusion, the
      trigger of acute pulmonary thrombosis in PHZ-treated rats was considered to be
      regional stasis resulting from blockage caused by the deformed erythrocytes, and
      subsequent systemic hemostatic disruption.

PMID- 22402173
TI  - Bone marrow and adipose stem cells can be tracked with PKH26 until post staining
      passage 6 in in vitro and in vivo.
AB  - Tracking of transplanted cells has become an important procedure in cell therapy.
      We studied the in vitro dye retention, survival and in vivo tracking of stem
      cells with PKH26 dye. Sheep BMSCs and ADSCs were labeled with 2, 4 and 8 MUmol of
      PKH26 and monitored for six passages. Labeled BMSCs and ADSCs acquired mean
      cumulative population doubling of 12.7+/-0.4 and 14.6+/-0.5; unlabeled samples
      had 13.8+/-0.5 and 15.4+/-0.6 respectively. Upon staining with 2, 4 and 8 MUmol
      PKH26, BMSCs had retentions of 40.0+/-5.8, 60.0+/-2.9 and 95.0+/-2.9%, while
      ADSCs had 92.0+/-1.2, 95.0+/-1.2 and 98.0+/-1.2%. ADSCs retentions were
      significantly higher at 2 and 4 MUmol. On dye retention comparison at 8 MUmol and
      4 MUmol for BMSCs and ADSCs; ADSCs were significantly higher at passages 2 and 3.
      The viability of BMSCs reduced from 94.0+/-1.2% to 90.0+/-0.6% and ADSCs from
      94.0+/-1.2% to 52.0+/-1.2% (p<0.05) after 24h. BMSCs had significant up
      regulation of the cartilage genes for both the labeled and the unlabeled samples
      compared to ADSCs (p<0.05). PKH26 fluorescence was detected on the resected
      portions of the regenerated neo-cartilage. The recommended concentration of PKH26
      for ADSCs is 2 MUmol and BMSCs is 8 MUmol, and they can be tracked up to 49 days.

PMID- 22402174
TI  - Amifostine, a radioprotectant agent, protects rat brain tissue lipids against
      ionizing radiation induced damage: an FTIR microspectroscopic imaging study.
AB  - Amifostine is the only approved radioprotective agent by FDA for reducing the
      damaging effects of radiation on healthy tissues. In this study, the protective
      effect of amifostine against the damaging effects of ionizing radiation on the
      white matter (WM) and grey matter (GM) regions of the rat brain were investigated
      at molecular level. Sprague-Dawley rats, which were administered amifostine or
      not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24
      h and the brain tissues of these rats were analyzed using Fourier transform
      infrared microspectroscopy (FTIRM). The results revealed that the total lipid
      content and CH(2) groups of lipids decreased significantly and the carbonyl
      esters, olefinic=CH and CH(3) groups of lipids increased significantly in the WM
      and GM after exposure to ionizing radiation, which could be interpreted as a
      result of lipid peroxidation. These changes were more prominent in the WM of the
      brain. The administration of amifostine before ionizing radiation inhibited the
      radiation-induced lipid peroxidation in the brain. In addition, this study
      indicated that FTIRM provides a novel approach for monitoring ionizing radiation
      induced-lipid peroxidation and obtaining different molecular ratio images can be
      used as biomarkers to detect lipid peroxidation in biological systems.

PMID- 22402175
TI  - Re: 'Myth: Group B streptococcal infection in pregnancy: comprehended and
      conquered' published in volume 16 (2011) pp 254-258.

PMID- 22402176
TI  - Modulation of macrophage activity by aflatoxins B1 and B2 and their metabolites
      aflatoxins M1 and M2.
AB  - Aflatoxins are natural contaminants frequently found both in food and feed. Many
      of them exert immunomodulatory properties in mammals; therefore, the aim of the
      current study was to investigate immune-effects of AFB1, AFB2, AFM1 and AFM2,
      alone and differently combined, in J774A.1 murine macrophages. MTT assay showed
      that AFB1, alone and combined with AFB2, possess antiproliferative activity only
      at the highest concentration; such effect was not shown by their hydroxylated
      metabolites, AFM1 and AFM2, respectively. However, the immunotoxic effects of the
      aflatoxins evaluated in the current study may be due to the inhibition of
      production of active oxygen metabolites such as NO. Cytofluorimetric assay in
      macrophages exposed to aflatoxins (10-100 MUM) revealed that their cytoxicity is
      not related to apoptotic pathways. Nevertheless, a significant increase of the S
      phase cell population accompanied by a decrease in G0/G1 phase cell population
      was observed after AFB1 treatment. In conclusion, the results of the current
      study suggest that aflatoxins could compromise the macrophages functions; in
      particular, co-exposure to AFB1, AFB2, AFM1 and AFM2 may exert interactions which
      can significantly affect immunoreactivity.

PMID- 22402177
TI  - Isolation of a Nav channel blocking polypeptide from Cyanea capillata medusae - a
      neurotoxin contained in fishing tentacle isorhizas.
AB  - Jellyfish are efficient predators which prey on crabs, fish larvae, and small
      fish. Their venoms consist of various toxins including neurotoxins that paralyse
      prey organisms immediately. One possible mode of action of neurotoxins is the
      blockage of voltage-gated sodium (Na(v)) channels. A novel polypeptide with Na(v)
      channel blocking activity was isolated from the northern Scyphozoa Cyanea
      capillata (L., 1758). For that purpose, a bioactivity-guided multidimensional
      liquid chromatographic purification method has been developed. A neurotoxic
      activity of resulting chromatographic fractions was demonstrated by a bioassay,
      which based on the mouse neuroblastoma cell line Neuro2A. The purification
      process yielded one fraction containing a single polypeptide with proven
      activity. The molecular weight of 8.22 kDa was determined by matrix-assisted
      laser desorption time-of-flight mass spectrometry (MALDI-ToF MS). Utilising Laser
      Microdissection and Pressure Catapulting (LMPC) for the separation of different
      nematocyst types in combination with direct MALDI-ToF MS analysis of the intact
      capsules, the neurotoxin was found to be present in all types of fishing tentacle
      isorhizas (A-isorhizas, a-isorhizas, O-isorhizas) of C. capillata medusae.

PMID- 22402178
TI  - Pulmonary function tests in obese people candidate to bariatric surgery.
AB  - Obesity is considered one of the most serious public health problems of the
      modern world. Because it alters the relationship between the lungs, chest wall
      and diaphragm, it is to be expected that it impacts on the respiratory function.
      In Portugal, there is not much data about the relationship between obesity and
      pulmonary function. The aim of this study was to characterize respiratory
      function in morbidly obese patients and to evaluate whether weight loss in
      patients submitted to bariatric surgery affects pulmonary function tests (PFT).
      We conducted a retrospective study with 36 morbidly obese patients submitted to
      bariatric surgery, with a mean age of 40.6 years, 64% female and with a mean body
      mass index (BMI) of 49.7 kg/m2. All patients were clinical and functionally
      evaluated before surgery and after their weight had stabilized following surgery.
      They underwent a complete pulmonary function testing with spirometry, lung
      volumes, carbon monoxide diffusing capacity (DLCO), maximum respiratory pressures
      and arterial blood gases analysis. Prior to surgery almost all the patients had
      functional respiratory changes, 34 had a decrease in functional residual capacity
      (FRC) 6 of whom a restrictive syndrome. Only 2 patients did not show any
      functional or arterial blood gas change. After bariatric surgery, BMI decreased
      to 34 kg/m2 and there was a significant improvement in almost all functional
      parameters with resolution of restrictive disorders. Nevertheless, in 13 patients
      the FRC remained decreased. After weight loss, the only correlation found was
      between reduction of BMI and increased FRC (r = -0.371; p = 0.028). This study
      suggests a relationship between obesity and pulmonary restriction and a positive
      impact of bariatric surgery in PFT.

PMID- 22402179
TI  - Pneumothorax, pneumomediastinum and pneumopericardium complications arising from
      a case of wisdom tooth extraction.
AB  - A 25-year-old woman underwent surgical tooth extraction. Several hours after the
      procedure, the woman complained of severe retrosternal pain and mild dyspnea.
      Subsequent imaging revealed subcutaneous emphysema from the mandibular region
      extending to the mediastinum and left side pneumothorax, as well as
      pneumopericardium. After treatment with antibiotics and analgesics, the patient
      recovered without any complications.

PMID- 22402180
TI  - An economic model to evaluate the mitigation programme for bovine viral diarrhoea
      in Switzerland.
AB  - Economic analyses are indispensable as sources of information to help policy
      makers make decisions about mitigation resource use. The aim of this study was to
      conduct an economic evaluation of the Swiss national mitigation programme for
      bovine viral diarrhoea virus (BVDV), which was implemented in 2008 and concludes
      in 2017. The eradication phase of the mitigation programme comprised testing and
      slaughtering of all persistently infected (PI) animals found. First, the whole
      population was antigen tested and all PI cattle removed. Since October 2008, all
      newborn calves have been subject to antigen testing to identify and slaughter PI
      calves. All mothers of PI calves were retested and slaughtered if the test was
      positive. Antigen testing in calves and elimination of virus-carriers was
      envisaged to be conducted until the end of 2011. Subsequently, a surveillance
      programme will document disease freedom or detect disease if it recurs. Four
      alternative surveillance strategies based on antibody testing in blood from
      newborn calves and/or milk from primiparous cows were proposed by Federal
      Veterinary Office servants in charge of the BVDV mitigation programme. A simple
      economic spreadsheet model was developed to estimate and compare the costs and
      benefits of the BVDV mitigation programme. In an independent project, the impact
      of the mitigation programme on the disease dynamics in the population was
      simulated using a stochastic compartment model. Mitigation costs accrued from
      materials, labour, and processes such as handling and testing samples, and
      recording results. Benefits were disease costs avoided by having the mitigation
      programme in place compared to a baseline of endemic disease equilibrium.
      Cumulative eradication costs and benefits were estimated to determine the break
      even point for the eradication component of the programme. The margin over
      eradication cost therefore equalled the maximum expenditure potentially available
      for surveillance without the net benefit from the mitigation programme overall
      becoming zero. Costs of the four surveillance strategies and the net benefit of
      the mitigation programme were estimated. Simulations were run for the years 2008
      2017 with 20,000 iterations in @Risk for Excel. The mean baseline disease costs
      were estimated to be 16.04 m CHF (1 Swiss Franc, CHF=0.73 ? at the time of
      analysis) (90% central range, CR: 14.71-17.39 m CHF) in 2008 and 14.89 m CHF (90%
      CR: 13.72-16.08 m CHF) in 2009. The break-even point was estimated to be reached
      in 2012 and the margin over eradication cost 63.15m CHF (90% CR: 53.72-72.82 m
      CHF). The discounted cost for each surveillance strategy was found to be smaller
      than the margin, so the mitigation programme overall is expected to have a
      positive net economic benefit irrespective of the strategy adopted. For economic
      efficiency, the least cost surveillance alternative must be selected.

PMID- 22402181
TI  - Aggregates and hydrogels prepared by self-assembly of amphiphilic copolymers with
      surfactants.
AB  - A series of water-insoluble polylactide/poly(ethylene glycol) (PLA/PEG) block
      copolymers were synthesized by ring-opening polymerization of lactide in the
      presence of mono- or dihydroxyl PEG, using nontoxic zinc lactate as catalyst.
      Interactions between the resulting copolymers and sodium dodecyl sulfate (SDS) in
      water were studied by varying SDS fraction and copolymer concentration, using
      ultraviolet-visible spectrometer. Light transmission results show that all the
      insoluble copolymers strongly interact with SDS, and the solubility of the
      copolymers is improved with increasing SDS fraction. Copolymers with triblock
      structures or higher molar masses present larger variation of solubility as
      compared to those with diblock structures or lower molar masses. Transmission
      electron microscopy and dynamic light scattering were then employed to examine
      the microstructure of aggregates in the mixture solutions. Various aggregates
      such as vesicles, branch-like micelles, spherical micelles, or nanogels were
      observed, depending on the SDS fraction and copolymer concentration. It is
      assumed that at low SDS fractions, surfactant molecules attach to PLA segments
      and make the copolymers more soluble to form various aggregates. At high SDS
      fractions, junctions composed of SDS aggregates with PLA segments involved inside
      are formed in the case of triblock copolymers and diblock ones with high molar
      masses. These junctions lead to cross-linking of copolymer chains to yield a
      nanogel. Hydrogels can be obtained at high concentrations as confirmed by
      rheological measurements.

PMID- 22402182
TI  - Aqueous mixtures of di-n-decyldimethylammonium chloride/polyoxyethylene alkyl
      ether: dramatic influence of tail/tail and head/head interactions on co
      micellization and biocidal activity.
AB  - Mixed aggregate formation and synergistic interactions of binary surfactant
      mixtures of di-n-decyldimethylammonium chloride, [DiC(10)][Cl], with
      polyoxyethylene alkyl ethers, C(i)E(j) (i=10, 12, j=4, 6, 8), have been
      investigated for various [DiC(10)][Cl]/C(i)E(j) ratios. The critical aggregation
      concentration of the binary mixtures has been determined by tensiometry, and the
      aggregate characteristics (i.e., size and composition, free ammonium
      concentration) have been estimated using the pulsed field gradient NMR
      spectroscopy and a [DiC(10)]-selective electrode. Diffusion coefficient
      measurements of micelles confirmed the synergistic interaction between the
      surfactants. It is thus shown that the formation of surface monolayers and mixed
      aggregates from [DiC(10)][Cl]/C(10)E(j) mixtures is driven by both tail/tail and
      head/head interactions, whereas [DiC(10)][Cl]/C(12)E(j) co-aggregation is mainly
      driven by tail/tail interactions. As a consequence, the co-aggregation phenomenon
      notably influences the biocidal activity of [DiC(10)][Cl] on the Candida albicans
      fungi. In the presence of C(12)E(j), the biocidal activity of the ammonium salt
      is inhibited due to the trapping of the cationic surfactants in the mixed
      aggregates, whereas in the presence of C(10)E(j), the biocidal activity of the
      surfactant mixture is maintained. The mode of action is also confirmed by a
      faster increase in the zeta potential of a C. albicans suspension in the presence
      of [DiC(10)][Cl]/C(10)E(8) than in the presence of [DiC(10)][Cl]/C(12)E(8).
      Therefore, a judicious adjustment of the alkyl (i) and polyoxyethylene (j) chain
      lengths of C(i)E(j) avoids its antagonistic effect on the biocidal activity of
      [DiC(10)][Cl].

PMID- 22402183
TI  - Catalysts for heterogeneous oxidation reaction based on metalloporphyrins
      immobilized on kaolinite modified with triethanolamine.
AB  - Raw kaolinite was modified with triethanolamine (TEA), in an attempt to create a
      new support for the immobilization of metalloporphyrins. Anionic
      metalloporphyrins containing Fe(3+) or Mn(3+) as metallic centers were
      immobilized on the prepared support, and the obtained solids were characterized
      by Fourier-transform infrared (FTIR) spectroscopy, X-ray powder diffraction
      (XRPD), thermal analysis (thermogravimetric and differential thermal analyses-
      TGA/DTA), and scanning electron microscopy (SEM). The solids were used in
      heterogeneous oxidation catalysis of cyclooctene and cyclohexane. The yields from
      the oxidation of cyclooctene depended on the amount of TEA and/or water present
      in the solids. Good reaction yields were obtained for the oxidation of
      cyclohexane, with selectivity for the alcohol. In one specific case, a possible
      co-catalytic activity was verified for TEA during the oxidation of cyclohexane.

PMID- 22402185
TI  - Investigation of porcine circovirus contamination in human vaccines.
AB  - DNA from porcine circovirus type 1 (PCV1) and 2 (PCV2) has recently been detected
      in two vaccines against rotaviral gastroenteritis from manufacturers A and B. We
      investigated if PCV1 sequences are present in other viral vaccines. We screened
      seeds, bulks and final vaccine preparations from ten manufacturers using qRT-PCR.
      We detected 3.8 * 103 to 1.9 * 107 PCV1 DNA copies/milliliter in live poliovirus
      seeds for inactivated polio vaccine (IPV) from manufacturer A, however, following
      inactivation and purification, the finished IPV was PCV1-negative. PCV1 DNA was
      not detectable in live polio preparations from other vaccine producers. There was
      no detectable PCV1 DNA in the measles, mumps, rubella and influenza vaccines
      analysed including material supplied by manufacturer A. We confirmed that the
      PCV1 genome in the rotavirus vaccine from manufacturer A is near full-length. It
      contains two mutations in the PCV cap gene, which may result from viral
      adaptation to Vero cells. Bulks of this vaccine contained 9.8 * 1010 to 1.8 *
      1011 PCV1 DNA copies/millilitre and between 4.1 * 107 and 5.5 * 108 DNA copies
      were in the final doses. We found traces of PCV1 and PCV2 DNA in the rotavirus
      vaccine from manufacturer B. This highlights the issue of vaccine contamination
      and may impact on vaccine quality control.

PMID- 22402184
TI  - Not all analogies are created equal: Associative and categorical analogy
      processing following brain damage.
AB  - Current research on analogy processing assumes that different conceptual
      relations are treated similarly. However, just as words and concepts are related
      in distinct ways, different kinds of analogies may employ distinct types of
      relationships. An important distinction in how words are related is the
      difference between associative (dog-bone) and categorical (dog-cat) relations. To
      test the hypothesis that analogical mapping of different types of relations would
      have different neural instantiations, we tested patients with left and right
      hemisphere lesions on their ability to understand two types of analogies, ones
      expressing an associative relationship and others expressing a categorical
      relationship. Voxel-based lesion-symptom mapping (VLSM) and behavioral analyses
      revealed that associative analogies relied on a large left-lateralized language
      network while categorical analogies relied on both left and right hemispheres.
      The verbal nature of the task could account for the left hemisphere findings. We
      argue that categorical relations additionally rely on the right hemisphere
      because they are more difficult, abstract, and fragile, and contain more distant
      relationships.

PMID- 22402186
TI  - Effect of betulinic acid on neutrophil recruitment and inflammatory mediator
      expression in lipopolysaccharide-induced lung inflammation in rats.
AB  - This study aimed to evaluate the effect of betulinic acid (BA) on acute lung
      damage induced by bacterial endotoxin (lipopolysaccharide, LPS) in male Sprague
      Dawley rats and explore its possible mechanisms. Oral administration of 25
      (mg/kg) BA started 7 days before LPS or saline nasal installation. Twenty-four
      hours after LPS or saline installation, samples of lung tissues were collected
      for determination of level of lipid peroxidation (MDA), reduced glutathione
      (GSH), superoxide dismutase (SOD), and expression of tumor necrosis-alpha (TNF
      alpha), transforming growth factor-beta1 (TGF-beta1) and inducible nitric oxide
      synthase (iNOS). Histopathology was done to examine pathological changes in
      lungs. Wet/dry (W/D) ratio and capillary protein leakage were also determined.
      Bronchoalveolar lavage (BAL) fluid was carried out for quantification of airway
      cellular inflammation and nitrate/nitrite (NOx) level. In comparison to BAL fluid
      samples from control animals, LPS-stimulated animals exhibited a higher count of
      the inflammatory cells and increased NOx levels. Lungs from LPS-treated animals
      showed increased lipid peroxidation, altered activities of antioxidant enzymes
      (GSH and SOD) and increased expression of TNF-alpha, TGF-beta1 and iNOS in
      comparison to lungs from control animals. LPS installation-induced pulmonary
      edema, manifested by significant increase in lung W/D ratio and Evans blue
      extravasation in lung tissue. This was supported by the histopathological
      examination which revealed markedly inflamed lung in LPS-treated animals.
      Treatment with BA was found to significantly attenuate all these alterations. The
      present results suggest that BA is endowed with antiinflammatory and antioxidant
      properties that protect the lung against the deleterious actions of LPS.

PMID- 22402187
TI  - The effects of kinesthetic illusory sensation induced by a visual stimulus on the
      corticomotor excitability of the leg muscles.
AB  - A novel method of visual stimulus, reported by Kaneko et al. [14], induced a
      vivid kinesthetic illusion and increased the corticomotor excitability of the
      finger muscles without any overt movement. To explore the effect of this method
      on the lower limbs, motor evoked potentials (MEP) were recorded from the left
      tibialis anterior (TA) and soleus muscles using transcranial magnetic stimulation
      (TMS). A computer screen that showed the moving image of an ankle movement was
      placed over the subject's leg, and its position was modulated to induce an
      illusory sensation that the subject's own ankle was moving (illusion condition).
      TMS was delivered at rest and at two different times during the illusion
      condition (ankle dorsiflexion phase: illusion-DF; ankle plantarflexion phase:
      illusion-PF). The MEP amplitude of the TA, which is the agonist muscle for ankle
      dorsiflexion, was significantly increased during the illusion-DF condition. This
      indicated that the visual stimulus showing the moving image of an ankle movement
      could induce a kinesthetic illusion and selectively increase the corticomotor
      excitability in an agonist muscle for an illusion, as was previously reported for
      an upper limb. The MEP amplitude of the soleus, which is the agonist muscle for
      ankle plantarflexion, increased during the illusion-PF condition, but not
      significantly. Because of the vividness of the illusory sensation was
      significantly greater during the illusion-DF condition than the illusion-PF
      condition, we concluded that the vividness of the illusory sensation had a
      crucial role in increasing corticomotor excitability.

PMID- 22402188
TI  - A meta-analysis of pro-inflammatory cytokines in the plasma of epileptic patients
      with recent seizure.
AB  - This review was to assess the concentration changing trends of various cytokines
      in plasma of epilepsy patients after recent seizure, as well as to assess the
      differences between temporal lobe epilepsy (TLE) and extra-TLE (XLE) patients. We
      performed a meta-analysis of studies measuring cytokine concentration in plasma
      of patients suffering from epilepsy after recent seizure, by searches of the
      English literature in Pubmed and Embase databases (to July 1st 2010) and a manual
      search of references. A random-effects model was used to do accumulative analysis
      for the included studies by RevMan 5.0 software. Eight studies were included and
      analyzed. We found the plasma concentrations of interleukin-6 (IL-6) within 72h
      after seizure were significantly increased in epileptic patients compared with
      control subjects (211 epilepsy patients vs. 564 controls, overall weighted mean
      difference 1.27pg/ml, 95% confidence interval 0.72-1.82, P<0.0001). There were no
      significant differences for IL-1 beta and, IL-1 receptor antagonist (IL-1RA)
      between the two groups. The concentration changes of IL-6 and IL-1RA were not
      significantly different between TLE patients and XLE patients. The result of this
      meta-analysis revealed significantly higher concentrations of the pro
      inflammatory cytokines IL-6 in epileptic seizure patients compared with control
      subjects. Further rigorous studies are needed to clarify the precise role of
      cytokines in epilepsy.

PMID- 22402189
TI  - Cilnidipine, an L/N-type calcium channel blocker prevents acquisition and
      expression of ethanol-induced locomotor sensitization in mice.
AB  - Several evidences indicated the involvement of L- and N-type calcium channels in
      behavioral effects of drugs of abuse, including ethanol. Calcium channels are
      implicated in ethanol-induced behaviors and neurochemical responses. Calcium
      channel antagonists block the psychostimulants induced behavioral sensitization.
      Recently, it is demonstrated that L-, N- and T-type calcium channel blockers
      attenuate the acute locomotor stimulant effects of ethanol. However, no evidence
      indicated the role of calcium channels in ethanol-induced psychomotor
      sensitization. Therefore, present study evaluated the influence of cilnidipine,
      an L/N-type calcium channel blocker on acquisition and expression of ethanol
      induced locomotor sensitization. The results revealed that cilnidipine (0.1 and
      1.0MUg/mouse, i.c.v.) attenuates the expression of sensitization to locomotor
      stimulant effect of ethanol (2.0g/kg, i.p.), whereas pre- treatment of
      cilnidipine (0.1 and 1.0MUg/mouse, i.c.v.) during development of sensitization
      blocks acquisition and attenuates expression of sensitization to locomotor
      stimulant effect of ethanol. Cilnidipine per se did not influence locomotor
      activity in tested doses. Further, cilnidipine had no influence on effect of
      ethanol on rotarod performance. These results support the hypothesis that
      neuroadaptive changes in calcium channels participate in the acquisition and the
      expression of ethanol-induced locomotor sensitization.

PMID- 22402190
TI  - Influence of somatosensory input on corticospinal excitability during motor
      imagery.
AB  - Our previous studies showed that corticospinal excitability during imagery of
      squeezing a foam ball was enhanced by somatosensory input generated by passively
      holding the ball. In the present study, using the same experimental model, we
      investigated whether corticospinal excitability was influenced by holding the
      object with the hand opposite to the imagined hand. Corticospinal excitability
      was assessed by monitoring motor evoked potentials (MEPs) in the first dorsal
      interosseous muscle following transcranial magnetic stimulation over the motor
      cortex during motor imagery. Subjects were asked to imagine squeezing a foam ball
      with the right hand (experiment 1) or the left hand (experiment 2), while either
      holding nothing (Null condition), a ball in the right hand (Right condition) or a
      ball in the left hand (Left condition). The MEPs amplitude during motor imagery
      was increased, only when the holding hand and the imagined hand were on the same
      side. These results suggest that performance improvement and rehabilitation
      exercises will be more effective when somatosensory stimulation and motor imagery
      are done on the same side.

PMID- 22402191
TI  - Functional response of hippocampal CA1 pyramidal cells to neonatal hypoxic
      ischemic brain damage.
AB  - Perinatal hypoxic-ischemic (H-I) is a major cause of brain injury in the newborn.
      The hippocampus is more sensitive to H-I injury than the other brain regions. It
      is believed that H-I brain damage causes a loss of neurons in the central nervous
      system. The patterns of neuronal death include apoptosis and necrosis. With
      regard to the responses of neurons, the neural functional changes should be
      earlier than the morphologic changes. The aim of the present study is to evaluate
      the electrophysiological characteristics and the synaptic transmission functions.
      Seven-day-old Sprague-Dawley rat pups were randomly divided into sham operation
      and H-I groups. The patch clamp, immunohistochemistry and Western blotting
      techniques were used to achieve this objective. The results of the study showed a
      decrease in neuronal excitability and a significant increase in the frequency of
      spontaneous excitatory postsynaptic currents and the duration of EPSCs in the CA1
      pyramidal cells of H-I brain damage rats. The glutamate transporter subtype 1
      (GLT-1) expression level of the hippocampal CA1 area in the H-I group was
      decreased compared with the control. There was no difference in the amplitude of
      excitatory postsynaptic currents and should be no difference in the expression of
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR), N
      methyl-D-aspartate receptor (NMDAR) and synaptophysin between the control and H-I
      brain injury group. These results revealed that changes of electrophysiological
      characteristics and synaptic functions occur instantly after H-I brain damage in
      the hippocampal pyramidal cells of neonatal rats. The failure to eliminate
      glutamate should be one of the important factors of excitotoxicity injury on
      hippocampal CA1 pyramidal cells, while neuronal excitation was not increased in
      the H-I brain injury model.

PMID- 22402192
TI  - [Usefulness and need for standardized criteria in diagnosing acute renal
      dysfunction in critical patients].

PMID- 22402193
TI  - [Coronary revascularization during cardiopulmonary resuscitation. The bridge
      code].
AB  - Cardiac arrest is one of the major current challenges, due to both its high
      incidence and mortality and the fact that it leads to severe brain dysfunction in
      over half of the survivors. The so-called coronary origin Bridge Code is
      presented, based on the international resuscitation recommendations (2005, 2010).
      In accordance with a series of strict predictive criteria, this code makes it
      possible to: (1) select refractory CPR patients with a high or very high
      presumption of underlying coronary cause; (2) evacuate the patient using
      mechanical chest compressors [LucasTM, Autopulse(r)], maintaining coronary and
      brain perfusion pressures; (3) allow coronary revascularization access during
      resuscitation maneuvering (PTCA during ongoing CPR); (4) induce early
      hypothermia; and (5) facilitate post-cardiac arrest intensive care. In the case
      of treatment failure, the quality of hemodynamic support makes it possible to
      establish a second bridge to non-heart beating organ donation.

PMID- 22402195
TI  - Characterization of a modified amplification approach for improved STR recovery
      from severely degraded skeletal elements.
AB  - Degraded skeletal remains generally contain limited quantities of genetic
      material and thus DNA-based identification efforts often target the mitochondrial
      DNA (mtDNA) control region due to the relative abundance of intact mtDNA as
      compared to nuclear DNA. In many missing person cases, however, the
      discriminatory power of mtDNA is inadequate to permit identification when
      associated anthropological, odontological, or contextual evidence is also
      limited, and/or the event involves a large number of individuals. In situations
      such as these, more aggressive amplification protocols which can permit recovery
      of STR data are badly needed as they may represent the last hope for conclusive
      identification. We have previously demonstrated the potential of a modified
      Promega PowerPlex 16 amplification strategy for the recovery of autosomal STR
      data from severely degraded skeletal elements. Here, we further characterize the
      results obtained under these modified parameters on a variety of sample types
      including pristine control DNA and representative case work specimens. Not only
      is the amplification approach evaluated here sensitive to extremely low authentic
      DNA input quantities (6 pg), but when the method was applied to thirty-one
      challenging casework specimens, nine or more alleles were reproducibly recovered
      from 69% of the samples tested. Moreover, when we independently considered bone
      samples extracted with a protocol that includes complete demineralization of the
      bone matrix, the percentage of samples yielding nine or more reproducible alleles
      increased to 95% with the modified amplification parameters. Overall, direct
      comparisons between the modified amplification protocol and the standard
      amplification protocol demonstrated that allele recovery was significantly
      greater using the aggressive parameters, with only a minimal associated increase
      in artifactual data.

PMID- 22402196
TI  - Segmentation of interest region in medical volume images using geometric
      deformable model.
AB  - In this paper, we present a new segmentation method using the level set framework
      for medical volume images. The method was implemented using the surface evolution
      principle based on the geometric deformable model and the level set theory. And,
      the speed function in the level set approach consists of a hybrid combination of
      three integral measures derived from the calculus of variation principle. The
      terms are defined as robust alignment, active region, and smoothing. These terms
      can help to obtain the precise surface of the target object and prevent the
      boundary leakage problem. The proposed method has been tested on synthetic and
      various medical volume images with normal tissue and tumor regions in order to
      evaluate its performance on visual and quantitative data. The quantitative
      validation of the proposed segmentation is shown with higher Jaccard's measure
      score (72.52%-94.17%) and lower Hausdorff distance (1.2654 mm-3.1527 mm) than the
      other methods such as mean speed (67.67%-93.36% and 1.3361mm-3.4463 mm), mean
      variance speed (63.44%-94.72% and 1.3361 mm-3.4616 mm), and edge-based speed
      (0.76%-42.44% and 3.8010 mm-6.5389 mm). The experimental results confirm that the
      effectiveness and performance of our method is excellent compared with
      traditional approaches.

PMID- 22402197
TI  - Active learning strategies for the deduplication of electronic patient data using
      classification trees.
AB  - INTRODUCTION: Supervised record linkage methods often require a clerical review
      to gain informative training data. Active learning means to actively prompt the
      user to label data with special characteristics in order to minimise the review
      costs. We conducted an empirical evaluation to investigate whether a simple
      active learning strategy using binary comparison patterns is sufficient or if
      string metrics together with a more sophisticated algorithm are necessary to
      achieve high accuracies with a small training set. MATERIAL AND METHODS: Based on
      medical registry data with different numbers of attributes, we used active
      learning to acquire training sets for classification trees, which were then used
      to classify the remaining data. Active learning for binary patterns means that
      every distinct comparison pattern represents a stratum from which one item is
      sampled. Active learning for patterns consisting of the Levenshtein string metric
      values uses an iterative process where the most informative and representative
      examples are added to the training set. In this context, we extended the active
      learning strategy by Sarawagi and Bhamidipaty (2002). RESULTS: On the original
      data set, active learning based on binary comparison patterns leads to the best
      results. When dropping four or six attributes, using string metrics leads to
      better results. In both cases, not more than 200 manually reviewed training
      examples are necessary. CONCLUSIONS: In record linkage applications where only
      forename, name and birthday are available as attributes, we suggest the
      sophisticated active learning strategy based on string metrics in order to
      achieve highly accurate results. We recommend the simple strategy if more
      attributes are available, as in our study. In both cases, active learning
      significantly reduces the amount of manual involvement in training data selection
      compared to usual record linkage settings.

PMID- 22402198
TI  - Cauda equina syndrome: an analysis of incidence rates and risk factors among a
      closed North American military population.
AB  - OBJECTIVE: This investigation attempted to determine the incidence of cauda
      equine syndrome (CES) within a closed North American population from 2001 to
      2010. This study also aimed to define risk factors influential in its
      development. METHODS: A search was performed using the Defense Medical
      Epidemiology Database and the ICD-9 code for CES (344.6). Demographic information
      including sex, race, military rank, branch of service, and age was obtained for
      the entire military population, as well as those diagnosed with CES. Incidence
      rates were calculated for the population as a whole, as well as for risk factors
      of interest. Multivariate Poisson regression analysis was utilized to identify
      significant risks while controlling for other factors in the model. RESULTS:
      Between 2001 and 2010, the incidence of CES in the military was 7 per 100,000
      person-years. Female sex was found to have the highest incidence rate at 0.15 per
      1000 person-years. Female sex, whites, individuals classified as other race,
      senior military rank, and age 30 and older were found to be significant risks for
      the development of CES. CONCLUSIONS: The results are in keeping with the findings
      of previous works, however, our cohort represents the largest number of patients
      with CES to be presented in the literature.

PMID- 22402199
TI  - Modified acrylic cranioplasty for large cranial defects.
AB  - OBJECTIVE: To describe a novel technique for constructing polymethylmethacrylate
      (acrylic) cranioplasty to repair large cranial defects. METHODS: A rim of bone is
      cut from the edge of the skull defect using a craniotome. This bony rim provides
      a scaffold to fashion the acrylic cement away from the patient thus avoiding
      thermal injury to the brain. The inner edge of the bony rim is drilled
      circumferencially to form a groove. Acrylic is then used to fill the defect in
      the bony rim with continuous manipulation of the paste from both sides to form a
      dome in the shape of the skull. The groove allows the edge of the acrylic dome to
      fit snugly with the bony rim thus avoiding sinking. The final cranioplasty,
      comprised of the hardened acrylic dome with the surrounding bone rim, is firmly
      attached to the skull with bioplates. RESULTS: We used the modified acrylic
      cranioplasty technique in three patients. Modified acrylic cranioplasty is
      cheaper and immediately available, compared with ten cases of titanium
      cranioplasty, with similar cosmetic outcome, intraoperative blood loss and
      operating theatre time. CONCLUSION: Our technique is quick and easy to perform,
      avoids thermal injury to the brain and produces a strong implant with excellent
      cosmesis even with large bony defects.

PMID- 22402200
TI  - Leptomeningeal carcinomatosis in aggressive germ non-seminoma testicular tumor: a
      case report and review of literature.

PMID- 22402194
TI  - New roles of carboxypeptidase E in endocrine and neural function and cancer.
AB  - Carboxypeptidase E (CPE) or carboxypeptidase H was first discovered in 1982 as an
      enkephalin-convertase that cleaved a C-terminal basic residue from enkephalin
      precursors to generate enkephalin. Since then, CPE has been shown to be a
      multifunctional protein that subserves many essential nonenzymatic roles in the
      endocrine and nervous systems. Here, we review the phylogeny, structure, and
      function of CPE in hormone and neuropeptide sorting and vesicle transport for
      secretion, alternative splicing of the CPE transcript, and single nucleotide
      polymorphisms in humans. With this and the analysis of mutant and knockout mice,
      the data collectively support important roles for CPE in the modulation of
      metabolic and glucose homeostasis, bone remodeling, obesity, fertility,
      neuroprotection, stress, sexual behavior, mood and emotional responses, learning,
      and memory. Recently, a splice variant form of CPE has been found to be an
      inducer of tumor growth and metastasis and a prognostic biomarker for metastasis
      in endocrine and nonendocrine tumors.

PMID- 22402201
TI  - Diagnosis and minimally invasive surgery for the pituitary abscess: a review of
      twenty nine cases.
AB  - OBJECTIVE: This study aimed to better determine the salient signs and symptoms
      for diagnosis of a pituitary abscess as well as the determination of the most
      appropriate treatment. METHODS: A retrospective analysis was performed using
      clinical presentations, imaging features, diagnosis and treatment of 29 patients
      with pituitary abscess in our hospital. RESULTS: We made the correct diagnosis of
      pituitary abscess before surgery only in 2 cases (13.3%) out of 15 patients
      between January 2004 and January 2008. While 12 cases (85.7%) out of 14 patients
      were correctly diagnosed before surgery between January 2008 and June 2010. All
      of the patients underwent transnasal-transsphenoidal surgery assisted by the
      microscope or endoscope. The antibiotic therapy and hormonal replacement were
      routinely administrated. The postoperative courses were uneventful and all
      symptoms of the patients were gradually improved one week to six months after
      surgery. None of the 29 cases were recurrent during the follow-up. CONCLUSION:
      With the increased clinical experience, the correct diagnosis rate of pituitary
      abscess before surgery has been greatly improved in recent three years. The
      microsurgical drainage, proper antibiotics and hormonal replacement are the keys
      to the treatment of pituitary abscess.

PMID- 22402202
TI  - Risk factor impact on blood flow velocities and clinical outcomes of stented
      cervical and intracranial stenoses: preliminary observations.
AB  - OBJECTIVES: The role of angioplasty/stenting procedures, neurointerventionist
      experience, vascular risk factors, medical treatment and blood flow velocities
      were analysed to identify possible causes of intra-stent restenosis (ISR)
      following stenting of cervical and/or intracranial arteries, assuming progressive
      atherosclerosis to be the shared mechanism in both territories. Patients. 26
      cerebrovascular patients subjected to stenting of severe (>=85%) symptomatic or
      asymptomatic carotid stenoses or moderate-to-severe (>=50%) intracranial or
      vertebral stenoses were included. METHODS: Clinical, radiological and
      ultrasonographic follow-up data were analysed retrospectively. RESULTS: Overall,
      stenting of the internal carotid artery (ICA) induced significant reductions in
      peak systolic velocities at 2 years (96+/-31 cm/s vs. 358.2+/-24.9 cm/s at
      baseline). The procedure-related ischemic complications rate was 7.4% (one
      hemispheric stroke and one TIA). The rate of ISR<=50% was 8% in the ICA at 2
      years; was 50% in the common carotid artery (CCA) at 1 year, with concomitant
      distal ICA stenosis in 75% of CCA stenting, but all ISR were asymptomatic.
      Patients with ISR of the ICA were significantly younger (56.8+/-4.5 vs. 71.3+/
      3.6 years, P=0.042) and had significantly more risk factors (5.5+/-0.9 vs. 3+/
      0.3, P=0.012). No ISR>=70% was detected. CONCLUSIONS: ISR is relatively
      infrequent and, when present, it is mild and asymptomatic. Restenosis is more
      frequent in younger patients and those with several risk factors, and it may also
      be related to stenting of previous carotid endarterectomy.

PMID- 22402203
TI  - Mollaret cells detected in a patient with varicella-zoster virus meningitis.

PMID- 22402204
TI  - Interferon, azathioprine and corticosteroids in multiple sclerosis: 6-year follow
      up of the ASA cohort.
AB  - OBJECTIVE: To evaluate long-term effects of 2-year treatment with interferon beta
      combined with low-dose azathioprine and prednisone in multiple sclerosis.
      METHODS: In the original 2-year ASA study, 181 patients with early relapsing
      remitting multiple sclerosis were randomised into 3 treatment arms: those treated
      with interferon beta (n=60), with interferon beta and low-dose azathioprine
      (n=58), and interferon beta, azathioprine and low-dose prednisone (n=63). Of
      these, 172 were included in this 4-year non-study extension. Three monthly
      clinical controls and annual MRI scans were carried out. The primary endpoint was
      annual relapse activity. The secondary endpoints were disability and quantitative
      MRI parameters. RESULTS: Nine patients were lost to follow-up and 172 were
      included in the analyses. None of relapse activity, disability accumulation or
      MRI parameters differed significantly between the groups over 6 years. Only 5.5%
      and 0.6% of patients were free from disease activity at year 2 and year 6 of the
      treatment initiation. CONCLUSION: The tested combined therapeutic regimen does
      not improve long-term outcomes in patients with multiple sclerosis. Furthermore,
      interferon is not able to completely abolish disease activity.

PMID- 22402205
TI  - Involvement of the prostate and testis expression (PATE)-like proteins in sperm
      oocyte interaction.
AB  - BACKGROUND: The prostate and testis expression (PATE)-like family of proteins are
      expressed mainly in the male genital tract. They are localized in the sperm head
      and are homologous to SP-10, the acrosomal vesicle protein also named ACRV1. Our
      aim was to characterize the expression and functional role of three PATE-like
      proteins in the testis and ejaculated sperm. METHODS: The expression and
      localization of PATE-like proteins in human testis biopsies (n= 95) and sperm
      cells were assessed by RT-PCR, immunohistochemistry and immunofluorescence
      staining (at least 600 sperm cells per specimen). The function of the PATE
      protein was tested by the hemizona assay and hamster egg penetration test (HEPT).
      RESULTS: PATE and PATE-M genes and proteins were present almost exclusively in
      germ cells in the testis: immunoflourescence showed that the percentage of germ
      cells positive for PATE, PATE-M and PATE-B was 85, 50 and 2%, respectively. PATE
      and PATE-M proteins were localized in the equatorial segment of the sperm head,
      while PATE-B protein was localized in the post-acrosomal region. A polyclonal
      antibody (Ab, at 1:50 and 1:200 dilutions) against the PATE protein did not
      inhibit sperm-zona binding in the hemizona assay (hemizona index of 89.6 +/- 10
      and 87 +/- 36%, respectively). However, there was inhibition of sperm-oolemma
      fusion and penetration in the HEPT (penetration index: without Ab 7 +/- 3.9; Ab
      dilution of 1:100, 4 +/- 3.5; Ab dilution of 1:20, 0.6 +/- 1.2, P < 0.001).
      CONCLUSIONS: Our data suggest that PATE protein is involved in sperm-oolemma
      fusion and penetration but not sperm-zona binding.

PMID- 22402206
TI  - Laeverin/aminopeptidase Q induces trophoblast invasion during human early
      placentation.
AB  - BACKGROUND: In primate placenta, extravillous trophoblast (EVT) invades maternal
      tissue in temporally- and spatially-regulated fashions. We previously identified
      a novel placenta-specific cell-surface aminopeptidase, laeverin/aminopeptidase Q,
      which is expressed on EVT-lineage cells in the fetal membrane. Laeverin possesses
      a peptide-binding site that is evolutionally unique to primates, suggesting
      possible involvement of laeverin in a primate-specific phenomenon during
      placentation. Thus, this study was designed to elucidate the molecular
      characteristics and physiological roles of laeverin in human EVT. METHODS:
      Placental tissues of various developmental stages were subjected to
      immunostaining and western blotting. Effects of siRNA and a soluble form of
      recombinant laeverin on EVT cells isolated from primary villous explant cultures
      were examined using Matrigel invasion assays and cell proliferation assays.
      RESULTS: Laeverin was specifically immunolocalized to HLA-G-positive EVT in
      placentas from early and term pregnancy. In primary villous explant cultures,
      laeverin expression was induced on the cell surface of the outgrowing EVT. In
      western blotting, laeverin protein was detected as two distinct bands at 130 and
      160 kDa along with a broad band ranging from 200 to 270 kDa. De-glycosylation
      treatment showed that these native laeverin isotypes are N-linked glycoproteins
      sharing a common 115-kDa core protein. In invasion assays, the reduction of
      laeverin expression by siRNA suppressed migration of the isolated EVT, while the
      soluble form of recombinant laeverin enhanced its migration. CONCLUSIONS:
      Laeverin is a specific cell-surface marker for human EVT and plays a regulatory
      role in EVT migration.

PMID- 22402207
TI  - Identification of specific vascular endothelial growth factor susceptible and
      protective haplotypes associated with recurrent spontaneous miscarriages.
AB  - BACKGROUND: We investigated the association of vascular endothelial growth factor
      (VEGF) gene polymorphism with recurrent spontaneous miscarriage (RSM). METHODS:
      VEGF -2578C/A, -1154G/A, -634G/C, +936C/T single nucleotide polymorphisms (SNPs)
      were assessed in 304 RSM patients, and 371 age-and body mass index-matched
      control subjects using real-time PCR. RESULTS: Higher minor allele frequency of 
      1154G/A (P < 0.001) and +936C/T (P < 0.001), but not -2578C/A (P = 0.55) or 
      634G/C (P = 0.87) SNPs, were seen in patients. Significant differences in the
      distribution of -1154G/A (P = 0.006) and +936C/T (P = 0.015), but not -2578C/A (P
      = 0.473) or -634G/C (P = 1.000) genotypes, were seen in cases compared with
      control women. Of the possible 16 VEGF haplotypes, 9 were found to be common, and
      were included. A significantly lower frequency of C G C C (P = 0.008), and A G G
      C (P < 0.001) haplotypes, and a higher frequency C G C T (P = 0.020), and C G T
      (P = 0.004) haplotypes were seen in patients. CONCLUSIONS: These results strongly
      support that VEGF polymorphisms, in particular-1154G/A and +936C/T, are
      significantly associated with RSM. Our results confirm, in the largest sample to
      date, previous works in other populations on VEGF polymorphism in RSM.

PMID- 22402208
TI  - Ethics of intergenerational (father-to-son) sperm donation.
AB  - In the ever changing field of reproductive medicine, clinics are regularly
      confronted with requests for novel variants of medically assisted reproduction.
      Particularly third-party (assisted) reproduction, which requires the involvement
      of an oocyte or sperm donor, is ethically and psychologically complex due to the
      parties involved, but nevertheless widely accepted. A particular type of third
      party reproduction concerns intrafamilial medically assisted reproduction (IMAR),
      where the donor is a family member of the recipients. In IMAR, some of the
      ethical and psychological issues associated with third party reproduction are
      intensified. The precise impact and consequences, however, remain speculative due
      to the lack of information regarding IMAR. Both the ESHRE Task Force on Ethics
      and Law and the Human Fertilization and Embryology Authority have recently
      highlighted the lack of information and the need for debate. In order to
      contribute to the discussion and knowledge on IMAR, we present a couple that
      recently visited our academic clinic with a request for a very particular variant
      of IMAR: first degree, intergenerational father-to-son sperm donation. As our
      academic hospital did not have experience with this variant of IMAR, our
      interdisciplinary Ethics Committee for Reproductive Medicine extensively
      discussed the request, resulting in an advisory report on the ethics of IMAR in
      general and father-to-son sperm donation in particular. Here, we will first
      present the andrological and social background of the couple and subsequently
      discuss the ethical considerations that led to the approval of their request. We
      will conclude the paper with recommendations for a morally sound practice of
      IMAR.

PMID- 22402209
TI  - Comparison of the phenotype of Chinese versus Dutch Caucasian women presenting
      with polycystic ovary syndrome and oligo/amenorrhoea.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex disorder with variable
      prevalence and clinical presentation in different populations, which may be
      mediated by geographical and ethnic background. METHODS: We performed a
      comparison of phenotypic characteristics between 547 Chinese and 427 Dutch women
      with PCOS and oligo/amenorrhoea attending University Reproductive Centers in
      China and the Netherlands. RESULTS: Chinese women presenting with a clinical
      diagnosis of PCOS were observed to have a higher incidence of hyperandrogenism
      (HA) (P < 0.001) and amenorrhoea (P < 0.001) compared with Dutch women, but no
      difference was observed in the incidence of polycystic ovaries (PCOs). Using
      population-specific cut-off values, Chinese women with PCOS demonstrated a higher
      incidence of increased BMI (P < 0.001), waist circumference (WC) (P < 0.001) and
      waist-hip ratio (P < 0.001) than Dutch women. In both groups, HA was associated
      with increased age, fasting insulin, homeostasis model assessment of insulin
      resistance (HOMA-IR) and serum LH while PCOs correlated with BMI, WC, HOMA-IR,
      fasting insulin and elevated total testosterone. Associations specific for ethnic
      background were found between LH and HA, and between both BMI and HOMA-IR, and
      PCOs. CONCLUSIONS: Reproductive and metabolic characteristics differed between
      the two ethnic groups. Chinese women were found to present more frequently with a
      phenotype associated with increased risk of metabolic complications later in
      life, compared with Dutch Caucasian women. Ethnicity seems to determine part of
      the specific phenotypical presentation of PCOS.

PMID- 22402210
TI  - Gene variations in sex hormone pathways and the risk of testicular germ cell
      tumour: a case-parent triad study in a Norwegian-Swedish population.
AB  - BACKGROUND: Testicular germ cell tumour (TGCT) is the most common cancer in young
      men, and an imbalance between the estrogen and androgen levels in utero is
      hypothesized to influence TGCT risk. Thus, polymorphisms in genes involved in the
      action of sex hormones may contribute to variability in an individual's
      susceptibility to TGCT. METHODS: We conducted a Norwegian-Swedish case-parent
      study. A total of 105 single-nucleotide polymorphisms (SNPs) in 20 sex hormone
      pathway genes were genotyped using Sequenom MassArray iPLEX Gold, in 831 complete
      triads and 474 dyads. To increase the statistical power, the analysis was
      expanded to include 712 case singletons and 3922 Swedish controls, thus including
      triads, dyads and the case-control samples in a single test for association.
      Analysis for allelic associations was performed with the UNPHASED program, using
      a likelihood-based association test for nuclear families with missing data, and
      odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. False
      discovery rate (FDR) was used to adjust for multiple testing. RESULTS: Five
      genetic variants across the ESR2 gene [encoding estrogen receptor beta (ERbeta)]
      were statistically significantly associated with the risk of TGCT. In the case
      parent analysis, the markers rs12434245 and rs10137185 were associated with a
      reduced risk of TGCT (OR = 0.66 and 0.72, respectively; both FDRs <5%), whereas
      rs2978381 and rs12435857 were associated with an increased risk of TGCT (OR =
      1.21 and 1.19, respectively; both FDRs <5%). In the combined case-parent/case
      control analysis, rs12435857 and rs10146204 were associated with an increased
      risk of TGCT (OR = 1.15 and 1.13, respectively; both FDRs <5%), whereas
      rs10137185 was associated with a reduced risk of TGCT (OR = 0.79, FDR <5%). In
      addition, we found that three genetic variants in CYP19A1 (encoding aromatase)
      were statistically significantly associated with the risk of TGCT in the case
      parent analysis. The T alleles of the rs2414099, rs8025374 and rs3751592 SNPs
      were associated with an increased risk of TGCT (OR = 1.30, 1.30 and 1.21,
      respectively; all FDRs <5%). We found no statistically significant differences in
      allelic effect estimates between parental inherited genetic variation in the sex
      hormone pathways and TGCT risk in the offspring, and no evidence of heterogeneity
      between seminomas and non-seminomas, or between the Norwegian and the Swedish
      population, in any of the SNPs examined. CONCLUSIONS: Our findings provide
      support for ERbeta and aromatase being implicated in the aetiology of TGCT.
      Exploring the functional role of the TGCT risk-associated SNPs will further
      elucidate the biological mechanisms involved.

PMID- 22402211
TI  - Therapeutic potential of andrographolide for treating endometriosis.
AB  - BACKGROUND: Mounting evidence shows that nuclear factor-kappaB (NF-kappaB) plays
      an important role in endometriosis. We therefore evaluated the therapeutic
      potential of andrographolide, an NF-kappaB inhibitor. METHODS: Primary cell
      cultures were performed using ectopic endometrial tissue specimens and their
      homologous eutopic endometrial specimens from 16 women with endometriosis, as
      well as control samples from 4 women without endometriosis. Andrographolide was
      evaluated for an effect on cell proliferation and cell cycle, DNA-binding
      activity of NF-kappaB and expression of cyclooxygenase-2 (COX-2) and tissue
      factor (TF). In a rat model of endometriosis, andrographolide treatment was
      evaluated for an effect on lesion size, hotplate response latency and expression
      of phosphorylated p50 and p65, COX-2 and nerve growth factor (NGF) in ectopic
      endometrium. RESULTS: Andrographolide dose dependently suppressed proliferation
      and cell cycle progression, attenuated DNA-binding activity of NF-kappaB in
      endometriotic stromal cells and inhibited COX-2 and TF expression. In the rat
      experiment, induced endometriosis resulted in reduced response latency.
      Andrographolide treatment significantly reduced lesion size in a dose-dependent
      manner and significantly increased response latency. Andrographolide treatment
      also significantly reduced immunoreactivity of COX-2, phosphorylated p50 and p65,
      and NGF in ectopic endometrium. CONCLUSIONS: Treatment with andrographolide
      significantly suppresses the growth of ectopic endometrium in vitro and in vivo,
      and results in a significant improvement in generalized hyperalgesia in rats with
      induced endometriosis. Therefore, andrographolide may be cytoreductive and may
      relieve pain symptoms in women with endometriosis. With excellent safety and cost
      profiles, andrographolide could be a promising therapeutic agent for
      endometriosis.

PMID- 22402212
TI  - Human testis steroidogenesis is inhibited by phthalates.
AB  - BACKGROUND: Phthalic acid esters are widely used in the manufacture of plastics.
      Numerous studies have shown that these phthalates impair testicular testosterone
      production in the rat. However, the scarce and contradictory data concerning
      humans have cast doubt over whether these compounds are also anti-androgenic in
      man. We therefore investigated the direct effects of di-(2-ethylhexyl) phthalate
      (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) on organo-cultured adult human
      testis and a human cell line. METHODS: Adult human testis explants or NCI-H295R
      adrenocortical human cells were cultured with DEHP or MEHP. The effects of
      ketoconazole, used as a reference molecule, were also assessed. RESULTS: In both
      models, DEHP and MEHP significantly inhibited testosterone production. The
      effects of both phthalates appeared to be specific for steroidogenesis, as INSL3
      production by Leydig cells was not altered. Furthermore, the phthalates of
      interest had no effect on inhibin B production by Sertoli cells or on germ cell
      apoptosis. As only a small fraction of the phthalates added was found in the
      testis explants, and as these compounds were found to be metabolized, we estimate
      that the anti-androgenic effects observed occurred at concentrations of
      phthalates that are of the same order of magnitude as exposures reported in the
      literature for men. CONCLUSIONS: We provide the first evidence that DEHP and MEHP
      can inhibit testosterone production in the adult human testis. This is consistent
      with recent epidemiological findings of an inverse correlation between exposure
      to MEHP and testosterone concentrations.

PMID- 22402213
TI  - Suggestions regarding a 'positive' vocabulary for embryo donation.

PMID- 22402215
TI  - Effects of extensive practice on bradykinesia in Parkinson's disease:
      improvement, retention and transfer.
AB  - We investigated the effects of extensive practice of rapid aiming on bradykinesia
      and, more specifically, generation of peak velocity, in discrete rapid aiming and
      in transfer to reach-to-grasp. Twenty-one participants (seven young adults, seven
      older adults, and seven adults with mild to moderate Parkinson's disease (PD)
      while on medication) engaged in eight practice periods per week for three weeks
      (> 700 trials), with changes in performance measured weekly. Retention was
      measured weekly for three weeks postpractice. Movement time decreased with one
      week of practice, primarily due to a decrease in time-to-peak velocity. With
      practice and after retention, the PD group generated peak velocity as
      consistently as both neurologically healthy groups, but remained more variable in
      time-to-peak velocity. Transfer was observed in the neurologically healthy
      groups, but not in the PD group. We concluded that short-term practice (one week
      in our paradigm) is sufficient for decreasing movement time, but more extensive
      practice is needed to improve consistency of rapid aiming performance for people
      with mild to moderate PD.

PMID- 22402214
TI  - Poly(Lactide-co-glycolide) ultrasonographic microbubbles carrying Sudan black for
      preoperative and intraoperative localization of lymph nodes.
AB  - Lymph node (LN) examination plays a critical role in the staging and treatment of
      several kinds of cancer such as lesions of the breast. However current strategies
      have limitations. This study aimed to develop a novel imaging agent, a polymeric
      ultrasonographic contrast agent carrying Sudan black (SB), for ultrasonographic
      imaging of the regional LNs before surgery and to directly localize the LNs
      during surgery. The poly(lactide-co-glycolide) (PLGA) ultrasonographic
      microbubbles carrying Sudan black B (SB) (SB-PLGA microbubbles) were prepared by
      the double emulsion method. The SB-PLGA microbubbles had a diameter of 1.5 +/-
      0.5 MUm and the SB encapsulation efficiency was (86.2 +/- 1.56%). Results from
      MTT assays suggested that these bubbles have little cytotoxicity to mouse
      macrophages after incubation. Confocal laser scanning microscopy showed that the
      PLGA microbubbles carrying the fluorescent dye rhodamine 6G were taken up by
      macrophages after 2-hour incubation. In addition, these SB-PLGA microbubbles were
      able to enhance ultrasonographic contrast of 12 popliteal LNs of 6 rabbits.
      Furthermore, the LNs were easily identifiable by the naked eye during surgery
      because of the blue color of the SB-PLGA microbubbles inside the LNs. By
      cryosectioning and hematoxylin and eosin (H&E) staining of LN tissue, our results
      showed that these SB-PLGA microbubbles were internalized inside the macrophages
      of the LNs. To conclude, the SB-PLGA microbubbles could be a suitable imaging
      agent for preoperative and intraoperative localization of LNs as well as for a
      preoperative ultrasonographically guided core needle biopsy of suspicious
      sentinel lymph nodes (SLNs) in cancer patients, hence enhancing treatment
      outcome.

PMID- 22402216
TI  - Amount of kinematic feedback affects learning of speech motor skills.
AB  - Knowledge of Performance (KP) feedback, such as biofeedback or kinematic
      feedback, is used to provide information on the nature and quality of movement
      responses for the purpose of guiding active learning or rehabilitation of motor
      skills. It has been proposed that KP feedback may interfere with long-term
      learning when provided throughout training. Here, twelve healthy English-speaking
      adults were trained to produce a trilled Russian [r] in words with KP kinematic
      feedback using electropalatography (EPG) and without KP (noKP). Five one-hour
      training sessions were provided over one week with testing pretraining and one
      day and one week posttraining. No group differences were found at pretraining or
      one day post training for production accuracy. A group by time interaction
      supported the hypothesis that providing kinematic feedback continually during
      skill acquisition interferes with retention.

PMID- 22402217
TI  - Exploring the thresholds of vision for perception and action.
AB  - Based upon evidence that vision for action has quicker access to visual
      information than vision for perception, we hypothesized that the two systems may
      have differentiated visual thresholds. There is also evidence that, unlike vision
      for perception, vision for action is insensitive to cognitive dual-task
      interference. Using visual masking, we determined the visual thresholds of 15
      participants in a perception task, an action task and an action plus concurrent
      cognitive secondary task. There was no difference in threshold between the
      perception task and the action task, but the action plus concurrent secondary
      task was accompanied by a greater visual threshold than both the perception task
      and the action task alone, indicating dual-task interference. The action task was
      thus most likely informed by vision for perception. The implications of these
      results are reviewed in the context of recent discussions of the two visual
      systems model.

PMID- 22402218
TI  - Examining impulse-variability in overarm throwing.
AB  - The purpose of this study was to examine variability in overarm throwing velocity
      and spatial output error at various percentages of maximum to test the prediction
      of an inverted-U function as predicted by impulse-variability theory and a speed
      accuracy trade-off as predicted by Fitts' Law Thirty subjects (16 skilled, 14
      unskilled) were instructed to throw a tennis ball at seven percentages of their
      maximum velocity (40-100%) in random order (9 trials per condition) at a target
      30 feet away. Throwing velocity was measured with a radar gun and interpreted as
      an index of overall systemic power output. Within-subject throwing velocity
      variability was examined using within-subjects repeated-measures ANOVAs (7
      repeated conditions) with built-in polynomial contrasts. Spatial error was
      analyzed using mixed model regression. Results indicated a quadratic fit with
      variability in throwing velocity increasing from 40% up to 60%, where it peaked,
      and then decreasing at each subsequent interval to maximum (p < .001, eta2 =
      .555). There was no linear relationship between speed and accuracy. Overall,
      these data support the notion of an inverted-U function in overarm throwing
      velocity variability as both skilled and unskilled subjects approach maximum
      effort. However, these data do not support the notion of a speed-accuracy trade
      off. The consistent demonstration of an inverted-U function associated with
      systemic power output variability indicates an enhanced capability to regulate
      aspects of force production and relative timing between segments as individuals
      approach maximum effort, even in a complex ballistic skill.

PMID- 22402219
TI  - From tremor to movement: differences in variability and coupling during bilateral
      finger actions.
AB  - This study examined changes in movement variability, coupling, and muscle
      activity across three different bilateral finger movements (e.g., postural,
      isometric, and isotonic). It was predicted that movements characterized by
      increased interlimb coupling would be associated with increased levels of muscle
      activity and reduced movement variability. The results demonstrated task-specific
      differences in interlimb relations with coupling being lowest during postural
      tasks and highest under isotonic conditions. However, a similar pattern was not
      observed for muscle activity and movement variability. Of the three tasks,
      postural tremor movements were more variable and had lower levels of muscle
      activity. Alternatively, increased muscle activity and more regular movement
      dynamics were seen under isometric conditions. Overall, it would appear that
      differences in bilateral coupling across tasks are not reflective of a single
      driving mechanism but rather reflect differential contribution from intrinsic
      neuromuscular and mechanical sources.

PMID- 22402220
TI  - Supervised resistance training results in changes in postural control in patients
      with multiple sclerosis.
AB  - Postural disturbances are one of the first reported symptoms in patients with
      Multiple Sclerosis (MS). The purpose of this study was to investigate the effect
      of supervised resistance training on postural control in MS patients. Postural
      control was assessed using amount of sway variability [Root Mean Square (RMS)]
      and temporal structure of sway variability [Lyapunov Exponent (LyE)] from 15 MS
      patients. Posture was evaluated before and after completion of three months of
      resistance training. There were significant differences between MS patients
      pretraining and healthy controls for both LyE (p = .000) and RMS (p = .002), but
      no differences between groups after training. There was a significant decrease in
      RMS (p = .025) and a significant increase in LyE (p = .049) for MS patients pre-
      to posttraining. The findings suggested that postural control of MS patients
      could be affected by a supervised resistance training intervention.

PMID- 22402222
TI  - Effect of head orientation on postural control during upright stance and forward
      lean.
AB  - Sensory feedback from the vestibular system and neck muscle stretch receptors is
      critical for the regulation of postural control. The postural relationship of the
      head to the trunk is a major factor determining the integration of sensory
      feedback and can be interfered with by varying head orientation. This study
      assessed how 60-s of standing with the head neutral, flexed, or extended impacted
      postural stability during upright stance and during forward lean in 13 healthy
      participants (26 +/-5 years old). During both quiet upright stance and maximal
      forward lean, head extension increased postural center of pressure (COP) velocity
      and decreased the COP time-to-contact the anterior stability boundary compared
      with the head neutral condition. Head flexion did not differ from head neutral
      for either of the stance conditions. This study demonstrates that interfering
      with the head-trunk relationship by adopting extended, but not flexed, head
      orientations interferes with postural control that may impact postural stability
      during both quiet upright stance and maximal forward lean conditions.

PMID- 22402221
TI  - The relationship between attention and gait in aging: facts and fallacies.
AB  - The current study critically assessed the relationship between cognitive
      functions and gait in nondemented older adults. Quantitative measures of gait
      (velocity, cadence, and a coefficient of variance in stride length) were assessed
      in single and dual-task conditions. Three cognitive factors captured the domains
      of Executive Attention, Verbal IQ, and Memory. Linear regressions showed that
      Executive Attention was related to velocity in both walking conditions. However,
      Memory and Verbal IQ were also related to velocity. Memory was related to Cadence
      in both walking conditions. Executive Attention was related to the coefficient of
      variance in stride length in both walking conditions. Linear mixed effects models
      showed that dual-task costs were largest in velocity followed by cadence and the
      coefficient of variance in stride length. The relationship between cognitive
      functions and gait depends, in part, on the analytic approach used, gait
      parameters assessed, and walking condition.

PMID- 22402223
TI  - Biomechanical analysis of postural strategies over the first two months following
      anterior cruciate ligament reconstruction.
AB  - To assess the postural strategies developed over the first 2 months following
      surgery by ACL patients during rehabilitation and highlight the sensory-motor
      impairment recovery, 21 patients were measured at three timeframes. Three two
      legged standing conditions were assessed: with the eyes open, with the eyes
      closed either wearing or not wearing a knee orthosis. The results indicate that
      the weight-bearing asymmetry, initially observed (i.e., 56-44% of body-weight),
      disappeared progressively during rehabilitation (51-49%). The comparison of the
      plantar center-of-pressure displacements under both sound and operated legs
      demonstrated noticeable differences that also tended to decrease but without
      reaching a matched behavior during the last measures. These effects were seen in
      both eyes open and eyes closed conditions with the greatest effects in the latter
      condition. Wearing a knee orthosis inferred no particular changes in the postural
      control behaviors. These data could be used as benchmarks for highlighting the
      effects on undisturbed postural control of various surgery techniques and/or
      rehabilitation protocols.

PMID- 22402224
TI  - The uptake of Cs and Sr from soil to radish (Raphanus sativus L.)- potential for
      phytoextraction and remediation of contaminated soils.
AB  - The (133)Cs and (88)Sr uptake by plant Raphanus sativus L. was studied during
      cultivation in outdoor potted-soil. The distribution, accumulation of (133)Cs,
      (88)Sr and the antioxidant responses in plants were measured after 30 and 60 days
      of cultivation. The results showed that the uptake capacity of radish for (88)Sr
      was far higher than that for (133)Cs when the concentration of (88)Sr was as the
      same as that of (133)Cs in the soil (The concentration of (88)Sr or (133)Cs in
      the soil was from 2.5 mg kg(-1) to 40 mg kg(-1)). The highest (88)Sr accumulation
      was 239.18 MUg g(-1) dw, otherwise, the highest (133)Cs accumulation was 151.74
      MUg g(-1) dw (The concentration of (88)Sr in the soil was 40 mg kg(-1)), and the
      lowest (88)Sr accumulation was 131.03 MUg g(-1) dw, otherwise, the lowest (133)Cs
      accumulation was 12.85 MUg g(-1) dw (The concentration of (88)Sr in the soil is 5
      mg kg(-1)). The (88)Sr and (133)Cs TF values were 1.16-1.72 and 0.24-0.60,
      respectively. There was little influence of high concentration of (88)Sr on the
      total biomass of plants, so the radish is one of the ideal phytoremediation plant
      for Sr polluted soils. The important physiological reasons that radish had good
      tolerance to (88)Sr stress were that the MDA content was higher under the (88)Sr
      stress than that under the (133)Cs stress, and the activities of POD and CAT were
      lower under the (88)Sr stress than that under (133)Cs stress.

PMID- 22402225
TI  - Electrochemical and infrared spectroscopic analysis of the interaction of the
      Cu(A) domain and cytochrome c(552) from Thermus thermophilus.
AB  - The hydrophobically guided complex formation between the Cu(A) fragment from
      Thermus thermophilus ba(3) terminal oxidase and its electron transfer substrate,
      cytochrome c(552), was investigated electrochemically. In the presence of the
      purified Cu(A) fragment, a clear downshift of the c(552) redox potential from 171
      to 111mV+/-10mV vs SHE' was found. Interestingly, this potential change fully
      matches complex formation with this electron acceptor site in other oxidases
      guided by electrostatic or covalent interactions. Redox induced FTIR difference
      spectra revealed conformational changes associated with complex formation and
      indicated the involvement of heme propionates. This article is part of a Special
      Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).

PMID- 22402226
TI  - Induction of the permeability transition pore in cells depleted of mitochondrial
      DNA.
AB  - Respiratory complexes are believed to play a role in the function of the
      mitochondrial permeability transition pore (PTP), whose dysregulation affects the
      process of cell death and is involved in a variety of diseases, including cancer
      and degenerative disorders. We investigated here the PTP in cells devoid of
      mitochondrial DNA (rho(0) cells), which lack respiration and constitute a model
      for the analysis of mitochondrial involvement in several pathological conditions.
      We observed that mitochondria of rho(0) cells maintain a membrane potential and
      that this is readily dissipated after displacement of hexokinase (HK) II from the
      mitochondrial surface by treatment with either the drug clotrimazole or with a
      cell-permeant HK II peptide, or by placing rho(0) cells in a medium without serum
      and glucose. The PTP inhibitor cyclosporin A (CsA) could decrease the
      mitochondrial depolarization induced by either HK II displacement or by nutrient
      depletion. We also found that a fraction of the kinases ERK1/2 and GSK3alpha/beta
      is located in the mitochondrial matrix of rho(0) cells, and that glucose and
      serum deprivation caused concomitant ERK1/2 inhibition and GSK3alpha/beta
      activation with the ensuing phosphorylation of cyclophilin D, the mitochondrial
      target of CsA. GSK3alpha/beta inhibition with indirubin-3'-oxime decreased PTP
      induced cell death in rho(0) cells following nutrient ablation. These findings
      indicate that rho(0) cells are equipped with a functioning PTP, whose regulatory
      mechanisms are similar to those observed in cancer cells, and suggest that escape
      from PTP opening is a survival factor in this model of mitochondrial diseases.
      This article is part of a Special Issue entitled: 17th European Bioenergetics
      Conference (EBEC 2012).

PMID- 22402227
TI  - Artificially produced [7-formyl]-chlorophyll d functions as an antenna pigment in
      the photosystem II isolated from the chlorophyllide a oxygenase-expressing
      Acaryochloris marina.
AB  - Acaryochloris marina, a chlorophyll (Chl) d-dominated cyanobacterium, is a model
      organism for studying photosynthesis driven by far-red light using Chl d.
      Furthermore, studies on A. marina may provide insights into understanding how the
      oxygenic photosynthetic organisms adapt after the acquisition of new Chl. To
      solve the reaction mechanism of its unique photosynthesis, photosystem (PS) II
      complexes were isolated from A. marina and analyzed. However, the lack of a
      molecular genetic method for A. marina prevented us from conducting further
      studies. We recently developed a transformation system for A. marina and we
      introduced a chlorophyllide a oxygenase gene into A. marina. The resultant
      transformant accumulated [7-formyl]-Chl d, which has never been found in nature.
      In the current study, we isolated PS II complexes that contained [7-formyl]-Chl
      d. The pigment composition of the [7-formyl]-Chl d-containing PS II complexes was
      1.96+/-0.04 Chl a, 53.21+/-1.00 Chl d, and 5.48+/-0.33 [7-formyl]-Chl d per two
      pheophytin a molecules. In contrast, the composition of the control PS II
      complexes was 2.01+/-0.06 Chl a and 62.96+/-2.49 Chl d. The steady-state
      fluorescence and excitation spectra of the PS II complexes revealed that energy
      transfer occurred from [7-formyl]-Chl d to the major Chl d species; however, the
      electron transfer was not affected by the presence of [7-formyl]-Chl d. These
      findings demonstrate that artificially produced [7-formyl]-Chl d molecules that
      are incorporated into PS II replace part of the Chl d molecules and function as
      the antenna. This article is part of a Special Issue entitled: Photosynthesis
      Research for Sustainability: from Natural to Artificial.

PMID- 22402228
TI  - The slow S to M fluorescence rise in cyanobacteria is due to a state 2 to state 1
      transition.
AB  - In dark-adapted plants and algae, chlorophyll a fluorescence induction peaks
      within 1s after irradiation due to well documented photochemical and non
      photochemical processes. Here we show that the much slower fluorescence rise in
      cyanobacteria (the so-called "S to M rise" in tens of seconds) is due to state 2
      to state 1 transition. This has been demonstrated in particular for Synechocystis
      PCC6803, using its RpaC(-) mutant (locked in state 1) and its wild-type cells
      kept in hyperosmotic suspension (locked in state 2). In both cases, the
      inhibition of state changes correlates with the disappearance of the S to M
      fluorescence rise, confirming its assignment to the state 2 to state 1
      transition. The general physiological relevance of the SM rise is supported by
      its occurrence in several cyanobacterial strains: Synechococcus (PCC 7942, WH
      5701) and diazotrophic single cell cyanobacterium (Cyanothece sp. ATCC 51142). We
      also show here that the SM fluorescence rise, and also the state transition
      changes are less prominent in filamentous diazotrophic cyanobacterium Nostoc sp.
      (PCC 7120) and absent in phycobilisome-less cyanobacterium Prochlorococcus
      marinus PCC 9511. Surprisingly, it is also absent in the phycobiliprotein rod
      containing Acaryochloris marina (MBIC 11017). All these results show that the S
      to M fluorescence rise reflects state 2 to state 1 transition in cyanobacteria
      with phycobilisomes formed by rods and core parts. We show that the pronounced SM
      fluorescence rise may reflect a protective mechanism for excess energy
      dissipation in those cyanobacteria (e.g. in Synechococcus PCC 7942) that are less
      efficient in other protective mechanisms, such as blue light induced non
      photochemical quenching. This article is part of a Special Issue entitled:
      Photosynthesis Research for Sustainability: from Natural to Artificial.

PMID- 22402229
TI  - The preoperative prediction of success following irrigation and debridement with
      polyethylene exchange for hip and knee prosthetic joint infections.
AB  - Although the criterion standard for the treatment of prosthetic joint infections
      (PJIs) is 2-stage revision with interim placement of an antibiotic-loaded spacer,
      irrigation and debridement with polyethylene exchange offer advantages such as
      fewer surgeries, reduced potential for intraoperative complications, and lower
      direct costs. The purpose of this study was to develop a tool to preoperatively
      predict the probability of successful infection eradication following irrigation
      and debridement with polyethylene exchange for hip or knee PJIs. A total of
      10,411 surgical cases were retrospectively reviewed, and data were collected from
      309 charts. Overall, 149 (48.2%) cases failed to eradicate the infection
      following irrigation and debridement with polyethylene exchange. Univariate
      analysis identified multiple variables independently associated with reinfection
      including duration of symptoms, preoperative inflammatory markers, and infecting
      organism. Logistic regression was used to generate a model (bootstrap-corrected
      concordance index of 0.645) to predict successful eradication of the infection,
      which was the basis for a nomogram. Using commonly obtained preoperative
      variables, the nomogram can be used to predict the probability of infection-free
      survival at 1, 2, 3, 4, and 5 years. Preoperative knowledge of the probability
      that a treatment strategy will eradicate a patient's PJI may improve risk
      assessment.

PMID- 22402230
TI  - Effect of preoperative rescue concomitant FUN/XUN-based chemo-radiotherapy for
      neoadjuvant chemotherapy-refractory breast cancer.
AB  - Even though tumor progression under neoadjuvant chemotherapy is uncommon, its
      locoregional management remains absolutely unclear. What is the best time for
      radical surgery or radiotherapy? "Rescue" chemo-radiotherapy could be a suitable
      radiosensitizing strategy to further reduce tumor progression and allow curative
      surgery while maintaining systemic therapy.

PMID- 22402231
TI  - Characteristics of the filled-in surface at the blind spot.
AB  - Our visual system can restore information missing within the portion of the
      retinal image corresponding to the blind spot where the optic nerve exits the
      eye. Previous studies of the properties of filled-in surfaces at the blind spot
      have found similarities and dissimilarities between filled-in and real surfaces
      and have therefore not provided a consistent view of the characteristics of the
      filled-in surface. First, we investigated whether filling-in utilizes a contour
      integration mechanism. Gratings with collinear lines filled in the blind spot
      more effectively than those both with orthogonal lines and without any line,
      suggesting that collinear facilitation underlies the filling-in of the blind
      spot. Second, the dynamics of binocular rivalry was examined by comparing the
      dominance duration distributions of filled-in and real surfaces. The results
      indicated that the strength of the filled-in surface was attenuated compared to
      that of the real surface during rivalry. Lastly, we tested whether travelling
      waves of dominance in rivalry could occur at the blind spot. The travelling waves
      could propagate through a hole only at the blind spot, suggesting that the filled
      in surface helps perceptual waves to travel across the blind spot. These results
      suggest that the filled-in surface shares a common mechanism via a horizontal
      connection but that it has weak strength to suppress the opposite eye during
      binocular viewing. 

PMID- 22402232
TI  - Voxel-based analysis of regional gray and white matter concentration in high
      myopia.
AB  - Structural changes of the brain have been detected in many early-onset eye
      diseases, whereas little is known about whether changes could occur if the onset
      age is after the sensitive development period. High Myopia is a prime example of
      neural plasticity after development, whose case history is usually long. To
      investigate potential morphological changes in the brain of high myopic patients,
      we compared a group of 30 adults with high myopia and 30 control subjects using
      high-resolution anatomic MRI in combination with vision tests. No difference in
      gray matter (GM) concentration was detected. However, increased concentration of
      white matter (WM) was observed in patients with high myopia, primarily in the
      calcarine area. Another three comparatively smaller regions were in the
      prefrontal and parietal lobe. It can be inferred that cortices developed normally
      and refractive error in high myopic patients may be compensated by strengthening
      the correlation between visual cortex and visual related areas. Our study
      suggests that besides early-onset diseases, the late-onset eye diseases can also
      affect the structure of brain. 

PMID- 22402233
TI  - The effect of mean luminance change and grating pedestals on contrast perception:
      model simulations suggest a common, retinal, origin.
AB  - The percept of a contrast target is substantially affected by co-occurring
      changes in mean luminance or underlying ("pedestal") contrast elements. These two
      types of modulatory effects have traditionally been studied as separate
      phenomena. However, regardless of different higher-level mechanisms, both classes
      of phenomena will necessarily also depend on shared mechanisms in the first
      stages of vision, starting with the primary responses of photoreceptors. Here we
      present model simulations showing that important aspects of both classes may be
      explained by the temporal dynamics of photoreceptor responses read by integrate
      and-fire operators. The model is physiologically justified and all its parameters
      are constrained by experimental evidence. Although there remains plenty of room
      for additional mechanisms to shape the exact quantitative realization of the
      perceptual functions in different situations, we suggest that signature features
      may be inherited from primary retinal signaling. 

PMID- 22402234
TI  - [Budgetary blues: more is not always better].

PMID- 22402235
TI  - [The mistake of austerity policies, including cuts, in the national health
      system].

PMID- 22402236
TI  - [Sociodemographic characteristics of induced abortions in Andalusia (Spain):
      differences between native and foreign populations].
AB  - OBJECTIVES: To describe the variables associated with induced abortions in
      Andalusia (Spain) and the differences between native and foreign populations.
      MATERIAL AND METHODS: A cross-sectional population-based study was carried out.
      The files on deliveries and induced abortions were combined to create a single
      file for the period 2007-2010. A binary logistic regression model was employed.
      The dependent variable was whether the pregnancy ended in delivery or induced
      abortion. The independent variables were the year, province of residence, number
      of previous children, schooling, cohabitation and nationality. The raw and
      adjusted odds ratios and the 95% confidence intervals were calculated for native
      and foreign women. RESULTS: Of 460,716 pregnancies, 17% ended in an induced
      abortion and 83% in delivery. The variables most closely associated with the risk
      of an induced abortion among native and foreign women in Andalusia were having
      three or more previous children (OR=23.06), being under 25 years old (OR=19.53),
      living alone (OR=10.04) and being an immigrant (OR=3.95), especially in African
      women. The rates of abortions, fecundity and fertility were higher in foreigners
      than in native women, with an increase in abortions and a decrease in fertility
      and fecundity. CONCLUSIONS: The women at greatest risk of having an abortion in
      Andalusia are young foreign women, especially those from Africa, who live alone,
      have previous children and secondary education and reside in the province of
      Huelva.

PMID- 22402237
TI  - [Colorectal cancer screening: actions have been taken and the cart has been put
      behind the horse].

PMID- 22402238
TI  - [Comment: regional inequality in healthcare for transsexual persons in Spain].

PMID- 22402239
TI  - Registered prevalence of borderline personality disorder in primary care
      databases.
AB  - OBJECTIVE: Borderline personality disorder (BPD) is a common personality
      disorder, with a population prevalence of 1.4-5.9%, although the epidemiology of
      this disorder in primary care is insufficiently known. Our objective was to
      determine the registered prevalence of BPD in primary care databases and to study
      the demographic and clinical characteristics of these patients. METHODS: We
      performed a cross-sectional study of the computerized databases of primary care
      clinical records. The target population consisted of all adults (>= 16 years old)
      registered in the Catalan Health Institute (n = 4,764,729). RESULTS: The
      prevalence of recorded BPD was 0.017%, and was higher in patients with other
      mental disorders, particularly substance-abuse disorders (0.161%). These patients
      had twice as many appointments with the general practitioner as the general
      population (8.1 vs. 4.4). CONCLUSION: The number of diagnoses of BPD recorded in
      primary care is extremely low, which contrasts with the available population
      based data.

PMID- 22402240
TI  - [The health status of older people with insomnia].
AB  - OBJECTIVES: To evaluate the perceived health status of elderly patients with
      insomnia, whether primary, secondary to a medical illness, or associated with
      another mental disorder. METHODS: We conducted a cross-sectional study in a
      representative sample of 926 persons aged over 65 years. A psychiatric interview
      was used to verify the presence of insomnia (DSM-IV-TR, Diagnostic and
      Statistical Manual of Mental Disorders, fourth ed., revised text). Interviews
      were conducted by health professionals to assess perceived health status (EuroQol
      5D), health problems, and socio-demographic characteristics. RESULTS: The
      prevalence of primary insomnia was 8.9% (95% CI: 7.1-11.0), that of insomnia
      associated with another mental disorder was 9.3% (95% CI: 7.5-11.4) and that of
      insomnia secondary to medical illness was 7.0% (95% CI: 5.4-8.9). Patients with
      insomnia who used hypnotics/sedatives scored lower in self-reported health (57.6;
      95% CI: 53.7-61.4), significantly lower (p<0.05) than participants with insomnia
      not taking these drugs (65.1; 95% CI: 53.7-61.4). The mean health status score in
      individuals without insomnia was 0.87 and was significantly lower (p<0.05) in
      persons with any type of insomnia: 0.80 in primary insomnia, 0.73 in insomnia
      secondary to a mental disorder and 0.76 in insomnia associated with medical
      illness. CONCLUSIONS: Health status was worse in older people with insomnia,
      whether primary, secondary to other mental illnesses or organic, and when the
      elderly patients consumed hypnotics/sedatives. Limitations were less severe in
      primary insomnia.

PMID- 22402241
TI  - [Organization of healthcare for transsexual persons in the Spanish national
      health system].
AB  - OBJECTIVE: Recognition of transexuality as a clinical entity for which medical
      attention should be available is currently a well-established reality, but
      institutional care has not been uniformly instituted throughout Spain. The aim of
      the present study was to determine the current situation of healthcare for
      transexualism in the publicly-funded health service in Spain. MATERIALS AND
      METHODS: A descriptive study based on data provided by the Spanish Society of
      Endocrinology Group on Identity and Sexual Differentiation was performed. The
      resources in the regions that have created specific gender units for these
      disorders are described. RESULTS: Nine autonomous regions (55%) have started to
      provide various procedures, although only four provide genitoplastic procedures.
      The first region to include all sex reassignment surgeries was Andalusia (year
      1999). At the same time, Madrid and Catalonia also began to provide specialized
      mental health care and endocrinology but did not include surgical procedures
      until 2007 and institutional recognition until 2008. Since 2007 other regions
      have incorporated healthcare for transsexual patients. Overall, 3,303 patients (a
      male-to female/female-to-male transsexual ratio of 1.9/1) and 864 surgical
      procedures have been registered in this study. The composition and proportion of
      working hours of specialists, as well as the kinds of treatments provided, differ
      widely in each region. CONCLUSIONS: The geographical distribution of healthcare
      to transsexual persons and the services provided vary. Few regions offer
      genitoplastic procedures. The number of applicants exceeds the number estimated
      by the national health system.

PMID- 22402242
TI  - Antiepileptic drugs and suicidality.
AB  - The current study is a systematic review of the literature concerning the
      possible relationship of antiepileptics and suicide-related clinical features and
      behaviours. A MEDLINE search returned 863 papers but only five were chosen as
      relevant. A critical analysis of the Food and Drug Administration report is also
      included. Overall, the current review suggests there are no convincing data
      concerning a 'class effect' of antiepileptics in inducing any type of suicide
      related behaviours. Further research is needed concerning topiramate, lamotrigine
      and maybe leviracetam. Clinicians are expected to inform patients and their
      families on the possible increased risk but it is important not to overemphasise
      the issue, since stopping or refusing to start antiepileptics may result in
      serious harm, including death of the patient. Future randomised controlled trials
      should specifically focus on issues concerning depression and suicidal thoughts
      in patients with epilepsy.

PMID- 22402243
TI  - Pomolic acid, triterpenoid isolated from Licania pittieri, as competitive
      antagonist of ADP-induced aggregation of human platelets.
AB  - Pomolic acid (PA), triterpenoid isolated from Licania pittieri, has previously
      shown a potent ability to inhibit adenosine diphosphate (ADP)- and epinephrine
      induced human platelet aggregation. To investigate whether PA could be an
      antagonist of ADP-activated receptors of human platelets (P2Y(1) and P2Y(12)),
      pharmacological studies were conducted to examining its ability to modulate the
      platelet shape change induced by a selective P2Y(1) receptor agonist MRS2365 and
      also the nature of its possible interaction with ADP receptors by analyzing the
      characteristics of log concentration-response curves of ADP constructed in the
      absence and in the presence of fixed concentrations of PA, using in vitro
      platelet aggregation assays. PA did not interfere with the activation of P2Y(1)
      receptor by MRS2365 to induce platelet shape change and displayed a competitive
      antagonism of ADP-induced platelet aggregation, which most probably involves
      competition for a single binding site in platelets. The estimated equilibrium
      dissociate constant (K(b)) of PA as ADP receptor antagonist was 15.4+/-0.06nM.
      Together, these findings give indirect evidence for the idea that PA could be a
      potent competitive antagonist of P2Y(12) receptor, and open the possibility to
      consider it as new member of the non-nucleotide generation of antiplatelet drugs.

PMID- 22402244
TI  - Protective effect of extract of Acanthopanax senticosus Harms on dopaminergic
      neurons in Parkinson's disease mice.
AB  - To study the neuroprotective effect of extract of Acanthopanax senticosus Harms
      against MPTP-induced mice model of Parkinson's disease and its mechanism. The
      Parkinson's disease mice model was induced by 1-Methyl-4-phenyl-1,2,3,6
      tetrahydropyridine Hydrochloride (MPTP-HCl, 30mg/kg daily for 5 days). High dose
      group and low dose group were medicated with extract of Acanthopanax senticosus
      Harms for 20 days, dose amounted to 182mg/kg and 45.5mg/kg daily respectively.
      The behavioral testing of mice was assessed using pole-climbing test. The levels
      of Dopamine (DA) and Homovanillic acid (HVA) in striatum were determined by Ultra
      performance liquid chromatography combined with time-of-flight mass spectrometry
      (UPLC-ToF-MS). The levels of dopamine receptor 1 and 2 in striatum were assayed
      simultaneously with the help of immunohistochemical method. The level of Caspase
      3 protein in substantia nigra was analyzed by Western Blot. From Day 5 during the
      administration of extract of Acanthopanax senticosus Harms, pole-climbing time in
      low and high dose group were significantly less than model group (p<0.05).
      Compared with model group, the DA level of striatum in low dose group was
      significantly higher (p<0.01), the number of dopamine receptor 1 and dopamine
      receptor 2-positive cells in low and high dose group were significantly less
      (p<0.05), the Caspase-3 protein level of substantia nigra in low and high dose
      group were significantly less (p<0.05). The neuroprotective effect of extract of
      Acanthopanax senticosus Harms may be able to protect C57BL/6 mice against MPTP
      induced dopaminergic neuronal damage.

PMID- 22402245
TI  - Effects of lavender oil inhalation on improving scopolamine-induced spatial
      memory impairment in laboratory rats.
AB  - Lavender is reported to be an effective medical plant in treating inflammation,
      depression, stress and mild anxiety in Europe and the USA. The present study
      investigated the effects of two different lavender essential oils from Lavandula
      angustifolia ssp. angustifolia Mill. (Lamiaceae) and Lavandula hybrida Rev.
      (Lamiaceae) on neurological capacity of male Wistar rats subjected to scopolamine
      (0.7mg/kg)-induced dementia rat model. Chronic exposures to lavender essential
      oils (daily, for 7 continuous days) significantly reduced anxiety-like behavior
      and inhibited depression in elevated plus-maze and forced swimming tests,
      suggesting anxiolytic and antidepressant activity. Also, spatial memory
      performance in Y-maze and radial arm-maze tasks was improved, suggesting positive
      effects on memory formation. Taken together, multiple exposures to lavender
      essential oils could effectively reverse spatial memory deficits induced by
      dysfunction of the cholinergic system in the rat brain and might provide an
      opportunity for management neurological abnormalities in dementia conditions.

PMID- 22402246
TI  - Evodiamine, a dual catalytic inhibitor of type I and II topoisomerases, exhibits
      enhanced inhibition against camptothecin resistant cells.
AB  - DNA topoisomerases are nuclear enzymes that are the targets for several
      anticancer drugs. In this study we investigated the antiproliferative activity
      against human leukaemia cell lines and the effects on topoisomerase I and II of
      evodiamine, which is a quinazolinocarboline alkaloid isolated from the fruit of a
      traditional Chinese medicinal plant, Evodia rutaecarpa. We report here the anti
      proliferative activity against human leukaemia cells K562, THP-1, CCRF-CEM and
      CCRF-CEM/C1 and the inhibitory mechanism on human topoisomerases I and II,
      important anti-cancer drugs targets, of evodiamine. Evodiamine failed to trap
      [Topo-DNA] complexes and induce any detectable DNA damage in cells, was unable to
      bind or intercalate DNA, and arrested cells in the G(2)/M phase. The results
      suggest evodiamine is a dual catalytic inhibitor of topoisomerases I and II, with
      IC(50) of 60.74 and 78.81 MUM, respectively. The improved toxicity towards
      camptothecin resistant cells further supports its inhibitory mechanism which is
      different from camptothecin, and its therapeutic potential.

PMID- 22402247
TI  - Synthesis, characterization and functional properties of low substituted
      acetylated corn starch.
AB  - Acetylated corn starch (ACS) was synthesized by the reaction of native corn
      starch (NCS) with acetic anhydride (AA) in an aqueous medium in the presence of
      sodium hydroxide as a catalyst. The factors that could affect the degree of
      substitution (DS) and reaction efficiency (RE) of corn starch were investigated
      which included the reaction temperature and time, the mass ratio of AA to starch,
      the ratio of the water volume to starch mass and pH. The optimal DS of 0.071 and
      RE of 67.05% was obtained. FTIR spectrometry showed new bands at 1733, 1375 and
      1252 cm(-1). The SEM of the ACS indicated some cavities on the granules which
      fused together, compared with NCS. Wide angle X-ray diffraction revealed that ACS
      had a similar profile as NCS (A type). However, the intensity of peaks were
      diminished. DSC thermograms exhibited that ACS had some lower gelatinization
      temperatures and enthalpies than NCS. The functional properties of ACS such as
      the swelling power, solubility, water absorption, clarity, freeze-thaw stability,
      retrogradation and viscosity were also studied. The results suggest that the ACS
      has much better functional properties than the NCS, and could be expected to have
      wide applications especially in food industry.

PMID- 22402248
TI  - Functional and immunochemical cross-reactivity of V2-specific monoclonal
      antibodies from HIV-1-infected individuals.
AB  - The recent analysis of the first successful RV144 vaccine trial revealed that a
      high titer of plasma anti-V2 antibodies (Abs) correlated with a decreased risk of
      HIV-1 infection in vaccine recipients. To understand the mechanism of immune
      correlates, we studied seven anti-V2 monoclonal Abs (mAbs) developed from HIV-1
      infected individuals. The V2 mAbs target conserved epitopes, including the
      binding site for alpha4beta7 integrin, and are broadly cross-reactive with
      various gp120 proteins. Preferential usage of the VH1-69 gene by V2 mAbs may
      depend on selection by the same antigenic structure. Six of seven V2 mAbs weakly
      neutralized four to eight of the 41 pseudoviruses tested and resistance to
      neutralization was correlated with longer V2 domains. The data suggest the
      presence of shared, conserved structural elements in the V2 loop, and these can
      be used in the design of vaccine immunogens inducing broadly reactive Abs with
      anti-viral activities.

PMID- 22402250
TI  - Recognition and repair of communicative failures: the interaction between Theory
      of Mind and cognitive complexity in schizophrenic patients.
AB  - The aim of the present research is to perform a detailed and empirical
      investigation of schizophrenia patients' deficits in recognizing and recovering a
      communicative failure. In particular, this paper investigates the role of Theory
      of Mind (ToM) and of the complexity of the mental representations involved in
      explaining patients' deficits in recognizing and recovering different kinds of
      communicative failures, i.e. failure of the expressive act, failure of
      communicative meaning and failure of the communicative effect. Twenty-two
      patients with schizophrenia and an equal number of healthy controls took part in
      the experiment. The experimental protocol consisted of videotaped stories in
      which two agents interact, showing a communicative failure; the participants were
      asked to recognize and repair the observed failure. Some classical ToM tests
      (Sally and Ann, Modified Smarties and a selection of six Strange Stories) were
      also administered. Our results revealed a deficit in patients, when compared with
      healthy controls, in recognizing and recovering communicative failures.
      Furthermore, focusing on schizophrenia patients' performance per se, we observed
      a trend with regard to the increasing difficulty of understanding and recognizing
      different kinds of communicative failures, i.e. failure of expression act,
      failure of communicative meaning, and failure of the communicative effect.
      LEARNING OUTCOMES: The reader becomes aware that schizophrenic patients perform
      less well than healthy controls in recognizing and recovering different kinds of
      communicative failures, and of the role played by Theory of Mind, and
      representational complexity involved in such different kinds of failures, in
      explaining patients' performance.

PMID- 22402249
TI  - Franceschetti hereditary recurrent corneal erosion.
AB  - PURPOSE: To describe new affected individuals of Franceschetti's original
      pedigree of hereditary recurrent erosion and to classify a unique entity called
      Franceschetti corneal dystrophy. DESIGN: Observational case series. METHODS: Slit
      lamp examination of 10 affected individuals was conducted. Biomicroscopic
      examinations were supplemented by peripheral corneal biopsy in 1 affected patient
      with corneal haze. Tissue was processed for light and electron microscopy and
      immunohistochemistry was performed. DNA analysis was carried out in 12 affected
      and 3 nonaffected family members. RESULTS: All affected individuals suffered from
      severe ocular pain in the first decade of life, attributable to recurrent corneal
      erosions. Six adult patients developed bilateral diffuse subepithelial
      opacifications in the central and paracentral cornea. The remaining 4 affected
      individuals had clear corneas in the pain-free stage of the disorder. Histologic
      and immunohistochemical examination of the peripheral cornea in a single patient
      showed a subepithelial, avascular pannus. There was negative staining with Congo
      red. DNA analysis excluded mutations in the transforming growth factor beta
      induced (TGFBI) gene and in the tumor-associated calcium signal transducer 2
      (TACSTD2) gene. CONCLUSION: We have extended the pedigree of Franceschetti
      corneal dystrophy and elaborated its natural history on the basis of clinical
      examinations. A distinctive feature is the appearance of subepithelial opacities
      in adult life, accompanied by a decreased frequency of recurrent erosion attacks.
      Its clinical features appear to distinguish it from most other forms of
      dominantly inherited recurrent corneal erosion reported in the literature.

PMID- 22402251
TI  - Measuring calcium signals and exocytosis in tissues.
AB  - BACKGROUND: Since the 1960s it has been clear that calcium is a key regulator of
      exocytosis. Early experiments directly showed that the secretory output was
      calcium dependent. But it has taken improvements in technology and clever
      experimentation to determine the relationships between the calcium signal and
      exocytosis. Today controversies still remain because of limitations in our
      ability to record both the calcium responses within the local domains that
      control secretion and in the methods used to record exocytosis. SCOPE OF REVIEW:
      Here the techniques used to measure calcium and exocytosis are reviewed with a
      distinction being drawn between measurements in excitable cells versus
      measurements in non-excitable cells. The review has a focus on techniques that
      are relevant to in vitro studies of native tissues and recent in vivo recordings.
      MAJOR CONCLUSIONS: There are a range of methods used to study the stimulus
      secretion pathway. Each presents their own advantages and drawbacks. These are
      discussed with reference to the latest work determining the factors controlling
      exocytosis in tissues. GENERAL SIGNIFICANCE: Stimulus-secretion coupling is the
      fundamental step in the control of neurotransmitter release, hormone secretion
      and protein secretion. Understanding secretory control is therefore important in
      understanding the physiological regulation of processes ranging from learning and
      memory to pancreatic secretion. Recent technological advances are now enabling us
      to study stimulus-secretion coupling within native tissues. This is helping us to
      understand the physiological complexities of secretory control. This article is
      part of a Special Issue entitled Biochemical, biophysical and genetic approaches
      to intracellular calcium signalling.

PMID- 22402253
TI  - Optical calcium imaging in the nervous system of Drosophila melanogaster.
AB  - BACKGROUND: Drosophila melanogaster is one of the best-studied model organisms in
      biology, mainly because of the versatility of methods by which heredity and
      specific expression of genes can be traced and manipulated. Sophisticated genetic
      tools have been developed to express transgenes in selected cell types, and these
      techniques can be utilized to target DNA-encoded fluorescence probes to
      genetically defined subsets of neurons. Neuroscientists make use of this approach
      to monitor the activity of restricted types or subsets of neurons in the brain
      and the peripheral nervous system. Since membrane depolarization is typically
      accompanied by an increase in intracellular calcium ions, calcium-sensitive
      fluorescence proteins provide favorable tools to monitor the spatio-temporal
      activity across groups of neurons. SCOPE OF REVIEW: Here we describe approaches
      to perform optical calcium imaging in Drosophila in consideration of various
      calcium sensors and expression systems. In addition, we outline by way of
      examples for which particular neuronal systems in Drosophila optical calcium
      imaging have been used. Finally, we exemplify briefly how optical calcium imaging
      in the brain of Drosophila can be carried out in practice. MAJOR CONCLUSIONS AND
      GENERAL SIGNIFICANCE: Drosophila provides an excellent model organism to combine
      genetic expression systems with optical calcium imaging in order to investigate
      principles of sensory coding, neuronal plasticity, and processing of neuronal
      information underlying behavior. This article is part of a Special Issue entitled
      Biochemical, Biophysical and Genetic Approaches to Intracellular Calcium
      Signaling.

PMID- 22402252
TI  - High glucose-induced Ca2+ overload and oxidative stress contribute to apoptosis
      of cardiac cells through mitochondrial dependent and independent pathways.
AB  - BACKGROUND: Cardiac cell apoptosis is the initiating factor of cardiac
      complications especially diabetic cardiomyopathy. Mitochondria are susceptible to
      the damaging effects of elevated glucose condition. Calcium overload and
      oxidative insult are the two mutually non-exclusive phenomena suggested to cause
      cardiac dysfunction. Here, we examined the effect of high-glucose induced calcium
      overload in calpain-1 mediated cardiac apoptosis in an in vitro setting. METHODS:
      H9c2, rat ventricular myoblast cell line was treated with elevated glucose
      condition and the cellular consequences were studied. Intracellular calcium
      trafficking, ROS generation, calpain-1 activation and caspase-12 and caspase-9
      pathway were studied using flow cytometry, confocal microscopy and Western blot
      analysis. RESULTS: High-glucose treatment resulted in increased intracellular
      calcium ([Ca2+]i) which was mobilized to the mitochondria. Concomitant intra
      mitochondrial calcium ([Ca2+]m) increase resulted in enhanced reactive oxygen and
      nitrogen species generation. These events led to mitochondrial dysfunction and
      apoptosis. Cardiomyocyte death exhibited several classical markers of apoptosis,
      including activation of caspases, appearance of annexin V on the outer plasma
      membrane, increased population of cells with sub-G0/G1 DNA content and nuclear
      condensation. Key findings include elucidation of cell signaling mechanism of
      high-glucose induced calcium-dependent cysteine protease calpain-1 activation,
      which triggers non-conventional caspases as alternate mode of cell death.
      CONCLUSION: This information increases the understanding of cardiac cell death
      under hyperglycemic condition and can possibly be extended for designing new
      therapeutic strategies for diabetic cardiomyopathy. GENERAL SIGNIFICANCE: The
      novel findings of the study reveal that high glucose induces apoptosis by both
      mitochondria-dependent and independent pathways via concomitant rise in
      intracellular calcium.

PMID- 22402254
TI  - The Mediator complex in thyroid hormone receptor action.
AB  - BACKGROUND: Mediator is an evolutionarily conserved multisubunit complex that
      plays an essential regulatory role in eukaryotic transcription of protein
      encoding genes. The human complex was first isolated as a transcriptional
      coactivator bound to the thyroid hormone receptor (TR) and has since been shown
      to play a key coregulatory role for a broad range of nuclear hormone receptors
      (NRs) as well as other signal-activated transcription factors. SCOPE OF REVIEW:
      We provide a general overview of Mediator structure and function, summarize the
      mechanisms by which Mediator is targeted to NRs, and outline recent evidence
      revealing Mediator as a regulatory axis for other distinct coregulatory factors,
      chromatin modifying enzymes and cellular signal transduction pathways. MAJOR
      CONCLUSIONS: Besides serving as a functional interface with the RNA polymerase II
      basal transcription machinery, Mediator plays a more versatile role in regulating
      transcription including the ability to: a) facilitate gene-specific chromatin
      looping events; b) coordinate chromatin modification events with preinitiation
      complex assembly; and c) regulate critical steps that occur during
      transcriptional elongation. The variably associated MED1 subunit continues to
      emerge as a pivotal player in Mediator function, not only as the primary
      interaction site for NRs, but also as a crucial interaction hub for other
      coregulatory factors, and as an important regulatory target for signal-activated
      kinases. GENERAL SIGNIFICANCE: Mediator plays an integral coregulatory role at NR
      target genes by functionally interacting with the basal transcription apparatus
      and by coordinating the action of chromatin modifying enzymes and transcription
      elongation factors. This article is part of a Special Issue entitled Thyroid
      hormone signalling.

PMID- 22402255
TI  - Spot diagnosis: eruptive melanocytic naevi during azathioprine therapy in Crohn's
      disease.

PMID- 22402256
TI  - Quantitative levonorgestrel plasma level measurements in patients with regular
      and prolonged use of the levonorgestrel-releasing intrauterine system.
AB  - BACKGROUND: The levonorgestrel-releasing intrauterine system (LNG-IUS) is well
      accepted as an easy-to-use contraceptive with an excellent side-effect profile.
      It contains a reservoir of 52 mg of levonorgestrel (LNG) with continuous release
      of the steroid. Its contraceptive use is approved for 5 years. The aim of this
      study was to determine the plasma concentration of LNG and its variation with
      time in patients with in-dwelling LNG-IUS Mirena(r). STUDY DESIGN: In this study,
      we determined LNG plasma concentrations in 110 women with LNG-IUS at different
      time points of use. Time from insertion of the system in the study population
      ranged from 20 days to 11.1 years. Quantitative LNG levels were determined using
      a validated liquid chromatography-tandem mass spectrometry assay. RESULTS: The
      mean+/-SD LNG plasma level in all women was 147+/-59 pg/mL. A highly significant
      negative correlation between LNG plasma level and LNG-IUS time of use could be
      demonstrated. In the first year of use, LNG plasma level was as high as 191+/-71
      pg/mL, decreasing to 157+/-68 pg/mL in the second year and 134+/-41 pg/mL in the
      third year. Even after exceeding the recommended period of LNG-IUS use, systemic
      LNG concentrations were detectable: 133+/-38 pg/mL in the sixth year, 133+/-48
      pg/mL in the seventh year and 117+/-45 pg/mL in the eighth year. Furthermore, a
      significant negative correlation between LNG plasma level and body mass index
      could be shown. CONCLUSION: Systemic LNG concentrations can be found in all
      patients with LNG-IUS IUS. However, concentrations are much lower than in other
      forms of LNG application. Moreover, this study demonstrates that a systemic
      effect of LNG-IUS can also be found after the recommended contraceptive lifespan
      of 5 years.

PMID- 22402257
TI  - Suppression of ovarian activity with a low-dose 21/7-day regimen oral
      contraceptive containing ethinylestradiol 20 mcg/drospirenone 3 mg in Japanese
      and Caucasian women.
AB  - BACKGROUND: Two studies assessed the effect of a low-estrogen-dose 21/7-day oral
      contraceptive containing ethinylestradiol and drospirenone (EE 20 mcg/drsp 3 mg)
      on ovarian activity in Japanese and Caucasian women. STUDY DESIGN: Study 1 was
      conducted in Japanese women (20-35 years), and Study 2 was conducted in Caucasian
      women (18-35 years). All women received EE 20 mcg/drsp 3 mg in a 21-day active
      pill regimen. The primary endpoint was the proportion of women with ovulation
      inhibition (Hoogland score <6; as assessed by transvaginal ultrasonography)
      during treatment cycle 2. RESULTS: Japanese (n=23) and Caucasian (n=30) women
      received two cycles of study treatment. During treatment cycle 2, ovulation was
      inhibited in 100% and 92.9% of Japanese and Caucasian women, respectively.
      CONCLUSIONS: EE 20 mcg/drsp 3 mg in a 21/7-day regimen provides comparable
      ovarian suppression in Japanese and Caucasian women, with normal ovarian function
      resuming shortly after treatment end in both populations.

PMID- 22402258
TI  - Randomized controlled trial of a computer-based module to improve contraceptive
      method choice.
AB  - BACKGROUND: Unintended pregnancy is common in the United States, and
      interventions are needed to improve contraceptive use among women at higher risk
      of unintended pregnancy, including Latinas and women with low educational
      attainment. STUDY DESIGN: A three-arm randomized controlled trial was conducted
      at two family planning sites serving low-income, predominantly Latina
      populations. The trial tested the efficacy of a computer-based contraceptive
      assessment module in increasing the proportion of patients choosing an effective
      method of contraception (<10 pregnancies/100 women per year, typical use).
      Participants were randomized to complete the module and receive tailored health
      materials, to complete the module and receive generic health materials, or to a
      control condition. RESULTS: In intent-to-treat analyses adjusted for recruitment
      site (n=2231), family planning patients who used the module were significantly
      more likely to choose an effective contraceptive method: 75% among those who
      received tailored materials [odds ratio (OR)=1.56; 95% confidence interval (CI):
      1.23-1.98] and 78% among those who received generic materials (OR=1.74; 95% CI:
      1.35-2.25), compared to 65% among control arm participants. CONCLUSIONS: The
      findings support prior research suggesting that patient-centered interventions
      can positively influence contraceptive method choice.

PMID- 22402259
TI  - Crosstalk between macrophages and smooth muscle cells in atherosclerotic vascular
      diseases.
AB  - Macrophages and smooth muscle cells (SMCs) represent major players in the
      pathogenesis of atherosclerotic vascular diseases. SMCs often reside in close
      proximity to macrophage clusters. Activated macrophages may promote pro
      atherogenic functions of SMCs. Addressing macrophage-dependent mechanisms of SMC
      activation may provide new insight into atherogenesis and new therapies for
      various vascular diseases. Direct evidence for such interplay between
      atherosclerosis-associated cell types, however, remains scant. While SMC-derived
      macrophage foam cells have long been reported, recent evidence has also
      identified SMC-like cells of monocyte origin, suggesting dynamic
      interchangeability of these cell types. Future efforts may help to understand the
      interplay between key cell types and offer new paradigms in vascular medicine and
      pharmacology.

PMID- 22402260
TI  - Microtubules are essential for guard-cell function in Vicia and Arabidopsis.
AB  - Radially arranged cortical microtubules are a prominent feature of guard cells.
      Guard cells expressing GFP-tubulin showed consistent changes in the appearance of
      microtubules when stomata opened or closed. Guard cells showed fewer microtubule
      structures as stomata closed, whether induced by transfer to darkness, ABA,
      hydrogen peroxide, or sodium hydrogen carbonate. Guard cells kept in the dark
      (closed stomata) showed increases in microtubule structures and stomatal aperture
      on light treatment. GFP-EB1, marking microtubule growing plus ends, showed no
      change in number of plus ends or velocity of assembly on stomatal closure. Since
      the number of growing plus ends and the rate of plus-end growth did not change
      when microtubule structure numbers declined, microtubule instability and/or
      rearrangement must be responsible for the apparent loss of microtubules. Guard
      cells with closed stomata showed more cytosolic GFP-fluorescence than those with
      open stomata as cortical microtubules became disassembled, although with a large
      net loss in total fluorescence. Microtubule-targeted drugs blocked guard-cell
      function in Vicia and Arabidopsis. Oryzalin disrupted guard-cell microtubules and
      prevented stomatal opening and taxol stabilized guard-cell microtubules and
      delayed stomatal closure. Gas exchange measurements indicated that the transgenes
      for fluorescent-labeled proteins did not disrupt normal stomatal function. These
      dynamic changes in guard-cell microtubules combined with our inhibitor studies
      provide evidence for an active role of microtubules in guard-cell function.

PMID- 22402261
TI  - Carbonylation and loss-of-function analyses of SBPase reveal its metabolic
      interface role in oxidative stress, carbon assimilation, and multiple aspects of
      growth and development in Arabidopsis.
AB  - Sedoheptulose-1,7-bisphosphatase (SBPase) is a Calvin cycle enzyme and functions
      in photosynthetic carbon fixation. We found that SBPase was rapidly carbonylated
      in response to methyl viologen (MV) treatments in detached leaves of Arabidopsis
      plants. In vitro activity analysis of the purified recombinant SBPase showed that
      SBPase was carbonylated by hydroxyl radicals, which led to enzyme inactivation in
      an H(2)O(2) dose-dependent manner. To determine the conformity with carbonylation
      caused loss in enzymatic activity in response to stresses, we isolated a loss-of
      function mutant sbp, which is deficient in SBPase-dependent carbon assimilation
      and starch biosynthesis. sbp mutant exhibited a severe growth retardation
      phenotype, especially for the developmental defects in leaves and flowers where
      SBPASE is highly expressed. The mutation of SBPASE caused growth retardation
      mainly through inhibition of cell division and expansion, which can be partially
      rescued by exogenous application of sucrose. Our findings demonstrate that ROS
      induced oxidative damage to SBPase affects growth, development, and chloroplast
      biogenesis in Arabidopsis through inhibiting carbon assimilation efficiency. The
      data presented here provide a case study that such inactivation of SBPase caused
      by carbonyl modification may be a kind of adaptation for plants to restrict the
      operation of the reductive pentose phosphate pathway under stress conditions.

PMID- 22402262
TI  - LOV domain-containing F-box proteins: light-dependent protein degradation modules
      in Arabidopsis.
AB  - Plants constantly survey the surrounding environment using several sets of
      photoreceptors. They can sense changes in the quantity (=intensity) and quality
      (=wavelength) of light and use this information to adjust their physiological
      responses, growth, and developmental patterns. In addition to the classical
      photoreceptors, such as phytochromes, cryptochromes, and phototropins, ZEITLUPE
      (ZTL), FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (FKF1), and LOV KELCH PROTEIN 2
      (LKP2) proteins have been recently identified as blue-light photoreceptors that
      are important for regulation of the circadian clock and photoperiodic flowering.
      The ZTL/FKF1/LKP2 protein family possesses a unique combination of domains: a
      blue-light-absorbing LOV (Light, Oxygen, or Voltage) domain along with domains
      involved in protein degradation. Here, we summarize recent advances in our
      understanding of the function of the Arabidopsis ZTL/FKF1/LKP2 proteins. We
      summarize the distinct photochemical properties of their LOV domains and discuss
      the molecular mechanisms by which the ZTL/FKF1/LKP2 proteins regulate the
      circadian clock and photoperiodic flowering by controlling blue-light-dependent
      protein degradation.

PMID- 22402263
TI  - Processes for the elimination of estrogenic steroid hormones from water: a
      review.
AB  - Natural estrogens such as estrone (E1), 17beta-estradiol (E2), estriol (E3), and
      the synthetic one, 17alpha-ethinylestradiol (EE2), are excreted by humans and
      animals and enter into environment through discharge of domestic sewage effluents
      and disposal of animal waste. The occurrence of these substances in aquatic
      ecosystems may affect the endocrine system of humans and wildlife so it has
      emerged as a major concern for water quality. Extensive research has being
      carried out during the last decades on the efficiency of the degradation and/or
      removal of these hormones in sewage treatment plants (STPs). Conventional and
      advanced treatments have been investigated by different authors for the
      elimination of estrogens from water. This paper aims to review the different
      processes and treatments that have been applied for the elimination of E1, E2, E3
      and EE2 from water. With this purpose, physical, biological and advanced
      oxidation processes (AOP) have been addressed.

PMID- 22402264
TI  - Biomechanical characterization of cervical spinal manipulation in living subjects
      and cadavers.
AB  - BACKGROUND: Cervical spinal manipulative therapy (cSMT) is a common therapeutic
      modality used in the treatment of neck pain and headaches. Cadaveric necks have
      been used as a model for assessing the effects of cSMT on vertebral artery
      mechanics. However, there have been no previous studies comparing the
      biomechanical indices of cSMT performed in living subjects versus cadavers.
      METHODS: The preload force, peak force and duration of cSMT performed by two
      chiropractors were recorded in 28 subjects with and without neck pain, and in
      five cadavers. RESULTS: There were no statistical differences in terms of the
      preload, peak force and duration of cSMT in living subjects with versus without
      neck pain. However, all three parameters differed statistically in living
      subjects versus cadavers; and both preload and peak forces were significantly
      higher for cadaveric cSMT; the average peak force was 190.3+/-85.5N (mean+/-SD)
      in living subjects, versus 283.9+/-53.6N in cadavers. Furthermore, the duration
      was significantly faster for cadaveric cSMT (175+/-100ms in living subjects
      versus 120+/-30ms in cadavers. These observations were consistent for both
      chiropractors. CONCLUSIONS: When performed in cadavers, cSMT tends to be more
      "aggressive" in terms of all biomechanical indices used to describe cSMT.

PMID- 22402265
TI  - Acute care surgery: the impact of an acute care surgery service on assessment,
      flow, and disposition in the emergency department.
AB  - BACKGROUND: Acute care surgery (ACS) services are becoming increasingly popular.
      METHODS: Assessment, flow, and disposition of adult ACS patients (acute,
      nontrauma surgical conditions) through the emergency department (ED) in a large
      health care system (Calgary) were prospectively analyzed. RESULTS: Among 447 ACS
      ED consultations over 3 centers (70% admitted to ACS), the median wait time from
      the consultation request to ACS arrival was 36 minutes, and from ACS arrival to
      the admission request it was 91 minutes. The total ACS-dependent time was 127
      minutes compared with 261 minutes for initial ED activities and 104 minutes for
      transfer to a hospital ward (P < .05). Forty percent of patients underwent
      computed tomography (CT) imaging (76% before consultation). The time to ACS
      consultation was 305 minutes when a CT scan was performed first. CONCLUSIONS: An
      ACS service results in rapid ED assessment of surgical emergencies. Patient
      waiting is dominated by the time before requesting ACS consultation and/or
      waiting for transfer to the ward.

PMID- 22402266
TI  - Beta-catenin expression is prognostic of improved non-small cell lung cancer
      survival.
AB  - INTRODUCTION: The objectives of this study were to determine the frequency and
      prognostic significance of beta-catenin expression in a cohort of non-small cell
      lung cancer (NSCLC) patients. METHODS: Tissue microarrays were constructed using
      clinically annotated formalin-fixed paraffin-embedded tumor samples from
      individuals diagnosed with NSCLC who underwent surgical resection with curative
      intent and had beta-catenin expression status determined by immunohistochemistry.
      RESULTS: Negative beta-catenin expression was seen in 28% (103/370) of NSCLC
      cases and was prognostic of a reduced overall patient survival (P = .008) and
      also was significantly correlated with the presence of lymphatic invasion (P =
      .015). In multivariate analysis, the loss of beta-catenin expression retained
      independent prognostic significance and showed an adjusted hazard ratio of 3.18
      (confidence interval, 1.46-6.91, P = .004) for reduced patient survival when
      adjusting for the presence of lymphatic invasion, tumor grade, nodal status, and
      tumor stage. CONCLUSIONS: Beta-catenin represents an important prognostic marker
      in individuals diagnosed with surgically resectable NSCLC.

PMID- 22402267
TI  - Membrane interactions of two arginine-rich peptides with different cell
      internalization capacities.
AB  - Cell penetrating peptides (CPPs) can cross cell membranes in a receptor
      independent manner and transport cargo molecules inside cells. These peptides can
      internalize through two independent routes: energy dependent endocytosis and
      energy independent translocation across the membrane, but the exact mechanisms
      are still unknown. The interaction of the CPP with different membrane components
      is certainly a preliminary key point that triggers internalization, such as the
      interaction with lipids to lead to the translocation process. In this study, we
      used two arginine-rich peptides, RW9 (RRWWRRWRR-NH2), which is a potent CPP, and
      RL9 (RRLLRRLRR-NH2) that, although binding tightly and accumulating on membranes,
      does not enter into cells. Using a set of experimental and theoretical
      techniques, we studied the binding, insertion and orientation of the peptides
      into different model membranes as well as the subsequent membrane reorganization.
      Herein we show that although the two peptides had rather similar behavior
      regarding lipid membrane interaction, subtle differences were found concerning
      the depth of peptide insertion, effect on the lipid chain ordering and kinetics
      of peptide insertion in the membrane, which altogether might explain their
      different cell internalization capacities. Molecular dynamics simulation studies
      show that some peptide molecules flipped their orientation over the course of the
      simulation such that the hydrophobic residues penetrated deeper in the lipid core
      region while Arg-residues maintained H-bonds with the lipid headgroups, serving
      as a molecular hinge in a conformation that appeared to correspond to the
      equilibrium one.

PMID- 22402268
TI  - Role of a conserved glycine triplet in the NSS amino acid transporter KAAT1.
AB  - K+-coupled amino acid transporter 1 (KAAT1) belongs to the NSS family of solute
      transporters and it is expressed in the midgut and in salivary glands of Manduca
      sexta larvae. As more than 80% of family members, KAATI shows a stretch of three
      glycines (G85-G87) that according to the structure of the prototype transporter
      LeuT, is located close to the access of the permeation pathway. In this work the
      role of the triplet has been investigated by alanine and cysteine scanning
      methods in protein heterologously expressed in Xenopus laevis oocytes. All the
      mutants were functional but the surface expression level was reduced for G85A and
      G87A mutants and unaffected for G86A mutant. All presented altered amino acid
      uptake and transport associated currents in the presence of each of the cations
      (Na+, K+, Li+) that can be exploited by the wt. G87A mutant induced increased
      uncoupled fluxes in the presence of all the cations. Cross-linking studies,
      performed by the treatment of cysteine mutants with the oxidative complex
      Cu(Il)(l,10-phenanthroline)3, showed that limiting the flexibility of the region
      by covalent blockage of position 87, causes a significant reduction of amino acid
      uptake. Na+ protected G87C mutant from oxidation, both directly and indirectly.
      The conserved glycine triplet in KAAT1 plays therefore a complex role that allows
      initial steps of cation interaction with the transporter.

PMID- 22402269
TI  - Comparison of the removal of hydrophobic trace organic contaminants by forward
      osmosis and reverse osmosis.
AB  - We compared the rejection behaviours of three hydrophobic trace organic
      contaminants, bisphenol A, triclosan and diclofenac, in forward osmosis (FO) and
      reverse osmosis (RO). Using erythritol, xylose and glucose as inert reference
      organic solutes and the membrane pore transport model, the mean effective pore
      size of a commercial cellulose-based FO membrane was estimated to be 0.74 nm.
      When NaCl was used as the draw solute, at the same water permeate flux of 5.4
      L/m(2) h (or 1.5 MUm/s), the adsorption of all three compounds to the membrane in
      the FO mode was consistently lower than that in the RO mode. Rejection of
      bisphenol A and diclofenac were higher in the FO mode compared to that in the RO
      mode. Because the molecular width of triclosan was larger than the estimated mean
      effective membrane pore size, triclosan was completely rejected by the membrane
      and negligent difference between the FO and RO modes could be observed. The
      difference in the separation behaviour of these hydrophobic trace organics in the
      FO (using NaCl the draw solute) and RO modes could be explained by the phenomenon
      of retarded forward diffusion of solutes. The reverse salt flux of NaCl hinders
      the pore diffusion and subsequent adsorption of the trace organic compounds
      within the membrane. The retarded forward diffusion effect was not observed when
      MgSO(4) and glucose were used as the draw solutes. The reverse flux of both
      MgSO(4) and glucose was negligible and thus both adsorption and rejection of BPA
      in the FO mode were identical to those in the RO mode.

PMID- 22402270
TI  - Comparison of different uncertainty techniques in urban stormwater quantity and
      quality modelling.
AB  - Urban drainage models are important tools used by both practitioners and
      scientists in the field of stormwater management. These models are often
      conceptual and usually require calibration using local datasets. The
      quantification of the uncertainty associated with the models is a must, although
      it is rarely practiced. The International Working Group on Data and Models, which
      works under the IWA/IAHR Joint Committee on Urban Drainage, has been working on
      the development of a framework for defining and assessing uncertainties in the
      field of urban drainage modelling. A part of that work is the assessment and
      comparison of different techniques generally used in the uncertainty assessment
      of the parameters of water models. This paper compares a number of these
      techniques: the Generalized Likelihood Uncertainty Estimation (GLUE), the
      Shuffled Complex Evolution Metropolis algorithm (SCEM-UA), an approach based on a
      multi-objective auto-calibration (a multialgorithm, genetically adaptive multi
      objective method, AMALGAM) and a Bayesian approach based on a simplified Markov
      Chain Monte Carlo method (implemented in the software MICA). To allow a
      meaningful comparison among the different uncertainty techniques, common criteria
      have been set for the likelihood formulation, defining the number of simulations,
      and the measure of uncertainty bounds. Moreover, all the uncertainty techniques
      were implemented for the same case study, in which the same stormwater quantity
      and quality model was used alongside the same dataset. The comparison results for
      a well-posed rainfall/runoff model showed that the four methods provide similar
      probability distributions of model parameters, and model prediction intervals.
      For ill-posed water quality model the differences between the results were much
      wider; and the paper provides the specific advantages and disadvantages of each
      method. In relation to computational efficiency (i.e. number of iterations
      required to generate the probability distribution of parameters), it was found
      that SCEM-UA and AMALGAM produce results quicker than GLUE in terms of required
      number of simulations. However, GLUE requires the lowest modelling skills and is
      easy to implement. All non-Bayesian methods have problems with the way they
      accept behavioural parameter sets, e.g. GLUE, SCEM-UA and AMALGAM have subjective
      acceptance thresholds, while MICA has usually problem with its hypothesis on
      normality of residuals. It is concluded that modellers should select the method
      which is most suitable for the system they are modelling (e.g. complexity of the
      model's structure including the number of parameters), their skill/knowledge
      level, the available information, and the purpose of their study.

PMID- 22402271
TI  - Innovative self-powered submersible microbial electrolysis cell (SMEC) for
      biohydrogen production from anaerobic reactors.
AB  - A self-powered submersible microbial electrolysis cell (SMEC), in which a
      specially designed anode chamber and external electricity supply were not needed,
      was developed for in situ biohydrogen production from anaerobic reactors. In
      batch experiments, the hydrogen production rate reached 17.8 mL/L/d at the
      initial acetate concentration of 410 mg/L (5 mM), while the cathodic hydrogen
      recovery ( [Formula: see text] ) and overall systemic coulombic efficiency
      (CE(os)) were 93% and 28%, respectively, and the systemic hydrogen yield (
      [Formula: see text] ) peaked at 1.27 mol-H(2)/mol-acetate. The hydrogen
      production increased along with acetate and buffer concentration. The highest
      hydrogen production rate of 32.2 mL/L/d and [Formula: see text] of 1.43 mol
      H(2)/mol-acetate were achieved at 1640 mg/L (20 mM) acetate and 100 mM phosphate
      buffer. Further evaluation of the reactor under single electricity-generating or
      hydrogen-producing mode indicated that further improvement of voltage output and
      reduction of electron losses were essential for efficient hydrogen generation. In
      addition, alternate exchanging the electricity-assisting and hydrogen-producing
      function between the two cell units of the SMEC was found to be an effective
      approach to inhibit methanogens. Furthermore, 16S rRNA genes analysis showed that
      this special operation strategy resulted same microbial community structures in
      the anodic biofilms of the two cell units. The simple, compact and in situ
      applicable SMEC offers new opportunities for reactor design for a microbial
      electricity-assisted biohydrogen production system.

PMID- 22402272
TI  - Characterisation of adsorbents prepared by pyrolysis of sludge and
      sludge/disposal filter cake mix.
AB  - Copper and zinc removal from water (pH = 5.0) using adsorbents produced from slow
      and fast pyrolysis of industrial sludge and industrial sludge mixed with a
      disposal filter cake (FC), post treated with HCl, is investigated in comparison
      with a commercial adsorbent F400. The results show that a pseudo-second order
      kinetics model is followed. The Langmuir-Freundlich isotherm model is found to
      fit the data best. The capacity for heavy metal removal of studied adsorbents is
      generally better than that of commercial F400. The dominant heavy metal removal
      mechanism is cation exchange. Higher heavy metal removal capacity is associated
      with fast pyrolysis adsorbents and sludge/FC derived adsorbents, due to enhanced
      cation exchange. Improvement of Zn(2+) removal via 1 N HCl post-treatment is only
      effective when exchangeable cations of the adsorbent are substituted with H(+)
      ions, which boost the cation exchange capacity. Increase of temperature also
      enhances metal removal capacity. Fast pyrolysis sludge-based adsorbents can be
      reused after several adsorption-desorption cycles.

PMID- 22402273
TI  - Degradation pathways of 4-methylmethcathinone in alkaline solution and stability
      of methcathinone analogs in various pH solutions.
AB  - Analogs of methcathinone (MC), a psychoactive stimulant, are in circulation all
      over the world. These analogs have been assumed to be unstable in alkaline
      solutions, as is MC itself. The aims of this study were: (i) to identify the
      degradation products of 4-methylmethcathinone (4-MMC), a typical MC analog, in
      solution at pH 12 and to determine the degradation pathway, (ii) to investigate
      the effects of antioxidants such as l-ascorbic acid and sodium sulfite on the
      degradation of 4-MMC, and (iii) to investigate the stability of seven MC analogs
      (4-MMC, 4-, 3-, or 2-fluoromethcathinone, 4-methoxymethcathinone, N
      ethylcathinone, and N,N-dimethylcathinone) in solutions at different pHs.1-(4
      Methylphenyl)-1,2-propanedione (MPPD), 4-methylbenzoic acid (MBA), N,4
      dimethylbenzamide (DMBA), and N-acetyl-4-MMC (N-Ac-4-MMC) were identified as the
      degradation products of 4-MMC in pH 12 solution by gas chromatography-mass
      spectrometry. There are two degradation pathways for 4-MMC as follows: (a) 4-MMC
      >MPPD->MBA->DMBA and (b) 4-MMC->N-Ac-4-MMC. Oxidants such as dissolved oxygen
      were presumed to be involved in this degradation based on the suppressive effects
      generated by the addition of antioxidants. All of the seven MC analogs tested
      were stable in acidic (pH 4) solution but degraded in neutral-to-basic solutions.
      Their degradation rates increased with increasing pH, and varied with their
      chemical structures. These findings will be very useful for not only forensic
      analysis but also future pharmacokinetic analysis.

PMID- 22402274
TI  - Viral nervous necrosis virus persistently replicates in the central nervous
      system of asymptomatic gilthead seabream and promotes a transient inflammatory
      response followed by the infiltration of IgM+ B lymphocytes.
AB  - The viral nervous necrosis virus (VNNV) is the causal agent of viral
      encephalopathy and retinopathy (VER), a worldwide fish disease that is
      responsible for high mortality in both marine and freshwater species. Infected
      fish suffer from encephalitis, which leads to abnormal swimming behavior and
      extensive cellular vacuolation and neuronal degeneration in the central nervous
      system (CNS) and retina. The marine fish gilthead seabream (Sparus aurata) does
      not develop VER but it is an asymptomatic carrier of VNNV. In this study, we
      report that VNNV was able to replicate and persist for up to 3 months in the CNS
      of the gilthead seabream without causing any neural damage. In addition, we found
      an early inflammatory response in the CNS that was characterized by the induction
      of genes encoding pro-inflammatory cytokines, a delayed but persistent induction
      of anti-inflammatory cytokines, and the infiltration of IgM(+) B lymphocytes,
      suggesting that local adaptive immunity played a major role in the control of
      VNNV in the CNS of this species.

PMID- 22402275
TI  - Ontogeny of anti-viral hemorrhagic septicemia virus (VHSV) immunity in developing
      Japanese flounder.
AB  - We examined the ability of developing Japanese flounder (Paralichthys olivaceus)
      to acquire protective immunity after exposure to viral hemorrhagic septicemia
      virus (VHSV). Juveniles measuring 9.8 cm average body length were not susceptible
      to infection with VHSV at 20  degrees C, while the smaller fish were susceptible.
      Mortality was not observed after secondary infection at 15  degrees C in the 9.8
      cm cohort that had previously been exposed to the virus at 20  degrees C, while
      the smaller fish were susceptible to secondary infection. The expression of
      interferon (IFN)-related genes was shown to be better developed in larger fish
      upon virus infection and basal expression levels of the virus recognition
      proteins were higher in larger fish. Virus-specific antibody was detected in the
      larger fish, but not in smaller fish. These data indicate that the largest
      juvenile (9.8 cm) acquired immunity against VHSV infection at the first virus
      challenge, but smaller fish did not. The anti-viral immune system in the Japanese
      flounder matures when juveniles reach approximately 10 cm.

PMID- 22402276
TI  - Characterisation and expression analysis of the rainbow trout (Oncorhynchus
      mykiss) homologue of the human dendritic cell marker CD208/lysosomal associated
      membrane protein 3.
AB  - LAMP3/CD208 is a member of the lysosomal-associated membrane protein family and
      is used as a putative marker for mature dendritic cells (DCs) in humans since it
      is upregulated upon DC activation and maturation. This paper reports the cloning
      and sequencing of LAMP3 in rainbow trout. The predicted trout LAMP3 shares the
      characteristic features of LAMP family members such as a C-terminal lysosomal
      sorting motif (G-Y-D-R-I) in the short C-terminal cytoplasmic tail, typical for
      lysosomal targeting, four potential N-linked glycosylation sites (NXS/T), four
      conserved cysteines in the membrane-proximal domain and the luminal domain
      divided by a serine/proline-rich region. Expression studies revealed that trout
      LAMP3, like chicken LAMP3, was constitutively expressed in a wide range of
      lymphoid tissues, at highest levels in the head kidney, liver and spleen,
      respectively. LAMP3 was also constitutively expressed in trout head kidney
      macrophages and RTS11 cells and the expression was shown to be induced in vivo
      after infection with viral and bacterial pathogens and in cultured macrophages
      after modulation with microbial mimics (LPS and PolyIC). Thus, it is clear that
      if LAMP3 is expressed by trout DCs it is not exclusively expressed by them.
      However, the marker is valuable to further study antigen presentation in fish and
      to complement already known DC markers.

PMID- 22402277
TI  - Movement pattern recognition in basketball free-throw shooting.
AB  - The purpose of the present study was to analyze the movement patterns of free
      throw shooters in basketball at different skill levels. There were two points of
      interest. First, to explore what information can be drawn from the movement
      pattern and second, to examine the methodological possibilities of pattern
      analysis. To this end, several qualitative and quantitative methods were
      employed. The resulting data were converged in a triangulation. Using a special
      kind of ANN named Dynamically Controlled Networks (DyCoN), a 'complex feature'
      consisting of several isolated features (angle displacements and velocities of
      the articulations of the kinematic chain) was calculated. This 'complex feature'
      was displayed by a trajectory combining several neurons of the network,
      reflecting the devolution of the twelve angle measures over the time course of
      each shooting action. In further network analyses individual characteristics were
      detected, as well as movement phases. Throwing patterns were successfully
      classified and the stability and variability of the realized pattern were
      established. The movement patterns found were clearly individually shaped as well
      as formed by the skill level. The triangulation confirmed the individual movement
      organizations. Finally, a high stability of the network methods was documented.

PMID- 22402278
TI  - Bio-effects and safety of low-intensity, low-frequency ultrasonic exposure.
AB  - Low-frequency (LF) ultrasound (20-100 kHz) has a diverse set of industrial and
      medical applications. In fact, high power industrial applications of ultrasound
      mainly occupy this frequency range. This range is also used for various
      therapeutic medical applications including sonophoresis (ultrasonic transdermal
      drug delivery), dentistry, eye surgery, body contouring, the breaking of kidney
      stones and eliminating blood clots. While emerging LF applications such as
      ultrasonic drug delivery continue to be developed and undergo translation for
      human use, significant gaps exist in the coverage of safety standards for this
      frequency range. Accordingly, the need to understand the biological effects of LF
      ultrasound is becoming more important. This paper presents a broad overview of
      bio-effects and safety of LF ultrasound as an aid to minimize and control the
      risk of these effects. Its particular focus is at low intensities where bio
      effects are initially observed. To generate a clear perspective of hazards in LF
      exposure, the mechanisms of bio-effects and the main differences in action at low
      and high frequencies are investigated and a survey of harmful effects of LF
      ultrasound at low intensities is presented. Mechanical and thermal indices are
      widely used in high frequency diagnostic applications as a means of indicating
      safety of ultrasonic exposure. The direct application of these indices at low
      frequencies needs careful investigation. In this work, using numerical
      simulations based on the mathematical and physical rationale behind the indices
      at high frequencies, it is observed that while thermal index (TI) can be used
      directly in the LF range, mechanical index (MI) seems to become less reliable at
      lower frequencies. Accordingly, an improved formulation for the MI is proposed
      for frequencies below 500 kHz.

PMID- 22402279
TI  - On the need to compare anomalous experiences carefully: commentary on Milan et
      al.'s Auras in mysticism and synaesthesia: a comparison.

PMID- 22402280
TI  - A new mechanism by which an acute type B aortic dissection is primarily
      complicated, becomes complicated, or remains uncomplicated.
AB  - BACKGROUND: This study is to evaluate if different locations of the primary entry
      tear result in primary complicated, secondary complicated, or uncomplicated acute
      type B aortic dissection. METHODS: Sixty-five patients were analyzed. Patients
      were stratified according to the location of the primary entry tear. Primary
      entry tears in axial computed tomographic scans at the upper circumference (180
      degrees ) of the distal aortic arch were defined as convex (group A) and the
      remaining as concave (group B). Detailed morphometry was done and the clinical
      outcome, including need for thoracic endovascular aortic repair, was evaluated.
      RESULTS: Forty-two patients (group A) had the primary entry tear at the convexity
      and 23 patients (group B) had the primary entry tear at the concavity of the
      distal aortic arch. There was a significant difference with regard to the
      incidence of primary complicated type B aortic dissection (group A 21% vs group B
      61%, p = 0.003) and with regard to the development of complications in group A (9
      days; 9 to 37) versus group B (0 days; 0 to 13, p = 0.03). Cox regression
      analysis revealed a primary entry tear at the concavity to be the only
      independent predictor of primary or secondary development of a complicated acute
      type B aortic dissection (hazard ratio, 1.8; 95% confidence interval, 1.0 to
      3.2). CONCLUSIONS: A primary entry tear at the concavity of the distal aortic
      arch is associated with a significant increase of the occurrence of complicated
      acute type B aortic dissection. Due to low procedural risk and high success
      rates, closure of the primary entry tear with thoracic endovascular aortic repair
      is strongly recommended in this newly defined high-risk subgroup of patients.

PMID- 22402281
TI  - Structural insights into the dual-targeting mechanism of Nutlin-3.
AB  - Multi-targeting therapy is an emerging strategy of drug discovery to improve
      therapeutic efficacy, safety and resistance profiles. In this study, we monitored
      the binding of a potent MDM2 inhibitor Nutlin-3 with anti-apoptotic Bcl-2 family
      proteins using NMR spectroscopy. Our results showed the universal binding of
      Nutlin-3 with diverse anti-apoptotic Bcl-2 family proteins. Taken together with
      the binding data for Nutlin-3 analogs, the structural model of the Bcl
      X(L)/Nutlin-3 complex showed that the binding mode of Nutlin-3 resembles that of
      the Bcl-X(L)/Bcl-2 inhibitors, suggesting the molecular mechanism of
      transcription-independent mitochondrial apoptosis by Nutlin-3. Finally, our
      structural comparison provides structural insights into the dual-targeting
      mechanism of how Nutlin-3 can bind to two different target proteins, MDM2 and
      anti-apoptotic Bcl-2 family proteins in a similar manner.

PMID- 22402282
TI  - Histone demethylase JMJD5 is essential for embryonic development.
AB  - Histone lysine methylation is pivotal in regulating chromatin structure and thus
      profoundly affects the transcriptome. JMJD5 (jumonji C domain-containing 5) is a
      histone demethylase that specifically removes methyl moieties from dimethylated
      lysine 36 on histone H3 and exerts a pro-proliferative effect on breast cancer
      cells. Here, we generated JMJD5 knockout mice in order to study the physiological
      significance of this enzyme. Whereas heterozygous knockout mice displayed no
      overt phenotype, homozygous JMJD5 knockouts died around day 10 of embryonal
      development. JMJD5(-/-) embryos showed delayed development already at E8.5 and
      were actively resorbed at E10.5. While strong JMJD5 expression was observed only
      in the yolk sac at E8.5, JMJD5 was robustly expressed in E10.5 embryos at several
      sites, including the heart and eye. Lack of JMJD5 resulted in transcriptional
      upregulation of the tumor suppressor p53. Concurrently, the cell cycle inhibitor
      p21 and the pro-apoptotic molecule Noxa, both of which are prominent p53 target
      genes, became strongly upregulated in JMJD5(-/-) embryos. Collectively, our data
      indicate that JMJD5 is essential during embryonal development and a repressor of
      p53 expression. The latter suggests that JMJD5 has oncogenic activity and
      accordingly JMJD5 is upregulated in leukemias and breast cancer.

PMID- 22402283
TI  - Endothelial RIG-I activation impairs endothelial function.
AB  - BACKGROUND: Endothelial dysfunction is a crucial part of the chronic inflammatory
      atherosclerotic process and is mediated by innate and acquired immune mechanisms.
      Recent studies suggest that pattern recognition receptors (PRR) specialized in
      immunorecognition of nucleic acids may play an important role in endothelial
      biology in a proatherogenic manner. Here, we analyzed the impact of endothelial
      retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial
      biology. METHODS AND RESULTS: Wild type mice were injected intravenously with
      32.5 MUg of the RIG-ligand 3pRNA (RNA with triphosphate at the 5'end) or polyA
      control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended
      vasodilation was significantly impaired, vascular oxidative stress significantly
      increased and circulating endothelial microparticle (EMP) numbers significantly
      elevated compared to controls. To gain further insight in RIG-I dependent
      endothelial biology, cultured human coronary endothelial cells (HCAEC) and
      endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both
      cells types express RIG-I and react with receptor upregulation upon stimulation.
      Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas
      apoptosis and proliferation is not significantly affected in HCAEC. Importantly,
      HCAEC release significant amounts of proinflammatory cytokines in response to RIG
      I stimulation. CONCLUSION: This study shows that activation of the cytoplasmatic
      nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced
      endothelial damage could therefore be an important pathway in atherogenesis.

PMID- 22402284
TI  - Interleukin-17 deficiency reduced vascular inflammation and development of
      atherosclerosis in Western diet-induced apoE-deficient mice.
AB  - OBJECTIVE: Several reports describe the role of interleukin (IL)-17 in the
      development of atherosclerosis; however, its precise role remains controversial.
      We generated double-deficient mice for apolipoprotein E (apoE) and IL-17 (apoE(-/
      )IL-17(-/-) mice) and investigated the effect of IL-17 deficiency on vascular
      inflammation and atherosclerosis. METHODS AND RESULTS: Atherosclerotic plaque
      areas in apoE(-/-)IL-17(-/-) mice fed a Western diet (WD) were significantly
      reduced compared with those in apoE(-/-) mice. No significant differences in
      plasma lipid profiles were observed between apoE(-/-) and apoE(-/-)IL-17(-/-)
      mice. The number of infiltrated macrophages in the plaques was significantly
      decreased in WD-fed apoE(-/-)IL-17(-/-) mice compared with WD-fed apoE(-/-) mice,
      whereas vascular smooth muscle cell content was not altered by IL-17 deficiency.
      Expression of inflammatory cytokines (MCP-1, IL-1beta, IL-6, IFN-gamma, and IL-12
      p40) and scavenger receptors (Msr-1, Scarb1, and Olr1) in the plaques was
      inhibited in WD-fed apoE(-/-)IL-17(-/-) mice. Furthermore, expression of
      inducible nitric oxide (M1 marker) and arginase-1 (M2 marker) was inhibited in WD
      fed apoE(-/-)IL-17(-/-) mice. CONCLUSION: Our results indicate that IL-17
      deficiency reduces vascular inflammation and atherosclerosis and that modulation
      of IL-17 could be a potential target for prevention and treatment of
      atherosclerosis.

PMID- 22402286
TI  - Molecular dynamics analysis of conformational change of paramyxovirus F protein
      during the initial steps of membrane fusion.
AB  - The fusion of paramyxovirus to the cell membrane is mediated by fusion protein (F
      protein) present in the virus envelope, which undergoes a dramatic conformational
      change during the process. Unlike hemagglutinin in orthomyxovirus, this change is
      not mediated by an alteration of environmental pH, and its cause remains unknown.
      Steered molecular dynamics analysis leads us to suggest that the conformational
      modification is mediated only by stretching mechanical forces once the
      transmembrane fusion peptide of the protein is anchored to the cell membrane.
      Such elongating forces will generate major secondary structure rearrangement in
      the heptad repeat A region of the F protein; from beta-sheet conformation to an
      elongated coil and then spontaneously to an alpha-helix. In addition, it is
      proposed that the heptad repeat A region adopts a final three-helix coiled coil
      and that this structure appears after the formation of individual helices in each
      monomer.

PMID- 22402285
TI  - Protein tyrosine nitration of mitochondrial carbamoyl phosphate synthetase 1 and
      its functional consequences.
AB  - Mitochondria are the primary locus for the generation of reactive nitrogen
      species including peroxynitrite and subsequent protein tyrosine nitration.
      Protein tyrosine nitration may have important functional and biological
      consequences such as alteration of enzyme catalytic activity. In the present
      study, mouse liver mitochondria were incubated with peroxynitrite, and the
      mitochondrial proteins were separated by 1D and 2D gel electrophoresis.
      Nitrotyrosinylated proteins were detected with an anti-nitrotyrosine antibody.
      One of the major proteins nitrated by peroxynitrite was carbamoyl phosphate
      synthetase 1 (CPS1) as identified by LC-MS protein analysis and Western blotting.
      The band intensity of nitration normalized to CPS1 was increased in a
      peroxynitrite concentration-dependent manner. In addition, CPS1 activity was
      decreased by treatment with peroxynitrite in a peroxynitrite concentration- and
      time-dependent manner. The decreased CPS1 activity was not recovered by treatment
      with reduced glutathione, suggesting that the decrease of the CPS1 activity is
      due to tyrosine nitration rather than cysteine oxidation. LC-MS analysis of in
      gel digested samples, and a Popitam-based modification search located 5 out of 36
      tyrosine residues in CPS1 that were nitrated. Taken together with previous
      findings regarding CPS1 structure and function, homology modeling of mouse CPS1
      suggested that nitration at Y1450 in an alpha-helix of allosteric domain prevents
      activation of CPS1 by its activator, N-acetyl-l-glutamate. In conclusion, this
      study demonstrated the tyrosine nitration of CPS1 by peroxynitrite and its
      functional consequence. Since CPS1 is responsible for ammonia removal in the urea
      cycle, nitration of CPS1 with attenuated function might be involved in some
      diseases and drug-induced toxicities associated with mitochondrial dysfunction.

PMID- 22402288
TI  - Central adiposity and Prostate Cancer in a Black Population.
AB  - BACKGROUND: The relationship between central adiposity and prostate cancer
      remains unclear. METHODS: This report includes 963 newly diagnosed cases of
      histologically confirmed prostate cancer and 941 randomly selected age-matched
      controls ascertained from the population-based Prostate Cancer in a Black
      Population study conducted between July 2002 and January 2011 in Barbados, West
      Indies. Trained nurse interviewers obtained data on height, weight, waist and hip
      circumferences, family and medical history, and lifestyle factors. ORs and 95%
      confidence intervals (CI) were used to assess associations between anthropometric
      measures and prostate cancer. RESULTS: A two-fold increased risk of prostate
      cancer was found among men in the highest quartile of waist-hip ratio compared
      with those in the lowest quartile (OR = 2.11, 95% CI, 1.54-2.88). Similarly, men
      with the largest waist circumferences had an OR of 1.84 (95% CI, 1.19-2.85)
      compared with those with the smallest waist sizes. CONCLUSIONS: These results
      suggest that measures of central rather than global adiposity may be more
      predictive of prostate cancer, especially in westernized African populations,
      where patterns of visceral fat distribution are different than other groups.
      IMPACT: The findings highlight the need to further elucidate the mechanisms
      underlying the relationship between central adiposity and prostate cancer in
      populations of predominantly African descent.

PMID- 22402289
TI  - Mammography screening and breast cancer mortality--letter.

PMID- 22402291
TI  - Examination, diagnosis and classification for Japanese allergic rhinitis:
      Japanese guideline.
AB  - Many countries throughout the world have experienced an increase in the
      prevalence of allergic rhinitis (AR), which has come to be a major cause of
      morbidity in developed countries. The pathology underlying AR is regarded as IgE
      mediated type I allergy characterized by mucosal inflammation that occurs in
      response to allergen exposure. In Japan, AR caused by Japanese cedar pollen, the
      most common allergic disease, has become a salient public health challenge.
      Almost all primary care physicians and otorhinolaryngologists have been consulted
      by AR patients between February and April. Although most such patients have
      received treatment, numerous patients with AR have not received proper
      examinations for AR. Clinical guidelines are systematically developed statements
      that are designed to help practitioners make decisions about appropriate and
      effective health care. Guidelines in many countries including Japan have been
      published for AR. Unfortunately, those guidelines have remained untested.
      Moreover, they might be difficult for non-specialists to use. In this review, we
      specifically examine the present standard examination for diagnosis of AR and
      optimal classification for AR in Japan. We hope that this review would be used
      not only for the support of daily practice but also for selection of AR patients
      for clinical trials.

PMID- 22402292
TI  - TACE with or without systemic therapy?

PMID- 22402290
TI  - Patient, hospital, and neighborhood factors associated with treatment of early
      stage breast cancer among Asian American women in California.
AB  - BACKGROUND: Clinical guidelines recommend breast-conserving surgery (BCS) with
      radiation as a viable alternative to mastectomy for treatment of early-stage
      breast cancer. Yet, Asian Americans are more likely than other groups to have
      mastectomy or omit radiation after BCS. METHODS: We applied polytomous logistic
      regression and recursive partitioning to analyze factors associated with
      mastectomy, or BCS without radiation, among 20,987 California Asian Americans
      diagnosed with stage 0 to II breast cancer from 1990 to 2007. RESULTS: The
      percentage receiving mastectomy ranged from 40% among U.S.-born Chinese to 58%
      among foreign-born Vietnamese. Factors associated with mastectomy included tumor
      characteristics such as larger tumor size, patient characteristics such as older
      age and foreign birthplace among some Asian Americans ethnicities, and additional
      factors including hospital [smaller hospital size, not National Cancer Institute
      cancer center, low socioeconomic status (SES) patient composition, and high
      hospital Asian Americans patient composition] and neighborhood characteristics
      (ethnic enclaves of low SES). These hospital and neighborhood characteristics
      were also associated with BCS without radiation. Through recursive partitioning,
      the highest mastectomy subgroups were defined by tumor characteristics such as
      size and anatomic location, in combination with diagnosis year and nativity.
      CONCLUSIONS: Tumor characteristics and, secondarily, patient, hospital, and
      neighborhood factors are predictors of mastectomy and omission of radiation
      following BCS among Asian Americans. IMPACT: By focusing on interactions among
      patient, hospital, and neighborhood factors in the differential receipt of breast
      cancer treatment, our study identifies subgroups of interest for further study
      and translation into public health and patient-focused initiatives to ensure that
      all women are fully informed about treatment options.

PMID- 22402293
TI  - Control of iron metabolism--lessons from neonatal hemochromatosis.

PMID- 22402294
TI  - Harvest of cortico-cancellous intramedullary femoral bone graft using the Reamer
      Irrigator-Aspirator (RIA).
AB  - The "Reamer-Irrigator-Aspirator" (RIA) is a device that provides continuous
      irrigation and aspiration during intramedullary reaming of long bones. The RIA
      system is first used to collect the reaming material from medullary cavities, a
      thick paste of finely morselized osseous particles containing significantly
      elevated levels of stem cells and growth factors as reported by quantitative
      analyses. The volume of bone graft material available from an adult femur
      corresponds to the amount of cancellous bone graft obtained from both the
      anterior and posterior iliac crests. The assembly and technicalities of the RIA
      system require a training period to prevent any femoral fracture, which appears
      to be the major RIA-related complication. The elective indications for RIA bone
      grafting are filling of bone defects in the epiphyseal and metaphyseal regions.
      Diaphyseal defects may also be managed using the RIA system provided the graft is
      placed in a constrained system (induced membrane) to prevent dispersion of the
      graft into the surrounding soft tissues and is aerated with a porous material to
      promote its revascularization. Other RIA indications include debriding
      intramedullary infections and reaming for intramedullary nailing of long bone
      fractures to reduce the risk of fat embolization.

PMID- 22402295
TI  - Comparison of the dental and skeletal effects of two different rapid palatal
      expansion appliances for the correction of the maxillary asymmetric transverse
      discrepancies.
AB  - AIM: The aim was to compare the skeletal and dental effects of a new type of a
      modified Hyrax rapid palatal expander with vestibular arm with the Hyrax expander
      in patients with maxillary asymmetric deficiencies. METHODS: This study includes
      50 growing patients in early mixed dentition, suffering from a maxillary
      narrowness combined with the exfoliation of one or more deciduous teeth, a
      monolateral or bilateral crossbite and a deviation of the upper midline. Twenty
      five patients were treated with a modified Hyrax expander and 25 patients with a
      Hyrax expander (RME). Dental casts and posteroanterior radiographs were obtained
      before treatment [T0] and six months after maxillary expansion [T1]. Measurements
      of intermolar width, intercanine width, arch length, arch perimeter, space
      between lateral incisor and I deciduous molar, and midline discrepancy were made
      with a digital calliper on photocopies taken from the dental casts. Cephalometric
      tracing on frontal teleradiographies were evaluated. RESULTS: Results showed no
      statistically significant differences between T0 and T1 in the modified RME
      appliance and the RME except lateral drift of incisor and space between lateral
      incisor and first deciduous molar. The modified RME permitted to obtain the
      restoration of the coincidence of the midlines of almost 5/6 mm and to create 7
      to 9 mm of space in the canine area. CONCLUSION: both the appliances are
      effective in correcting maxillary narrowness but the modified hyrax expander
      represents the best choice for the correction of upper midline deviations, and to
      restore the correct symmetry of dental midlines.

PMID- 22402296
TI  - Influence of cutting instruments and adhesive systems on hybrid layer formation.
AB  - Influence of cutting instruments and The aim of this study was to analyze the
      hybrid layer in noncarious dentin prepared by different cutting instruments and
      restored with composite resin. The cavities were randomly prepared in 40
      specimens using a high-speed diamond bur (KG Sorensen 1013) and an ultrasonic tip
      (CVDentus C22). The cavities were restored with composite resin by varying the
      adhesive system between the AdperTM Single Bond (2 x 1 system, primer+adhesive)
      and the Prompt L-PopTM (3 x 1 system, self-etching). The restorations were
      hemisected longitudinally and analyzed in the SEM (Scanning electron microscopy)
      in order to evaluate the hybrid layer and resinous tags characteristics, using
      scores ranging from 1 to 6. The Pearson test revealed a high correlation
      coefficient and good significance levels for both intra- and inter-raters values
      (r=0.90). The data were statistically analyzed using the Mann-Whitney test
      (P<=0.05). A larger proportion of regular hybrid layers with numerous tags were
      observed in the dentin prepared using the high-speed diamond burs and restored
      with a 2 * 1 adhesive system. Alternatively, the 3 * 1 adhesive system promoted
      the generation of a thin hybrid layer with few tags. After preparation using an
      ultrasonic tip revealed few or no tags after the preparation and 2 * 1 or 3 * 1
      adhesive system application. The high-speed diamond burs produced a dentin
      surface that was more favorable to restorative material adhesion than the
      ultrasonic tips, regardless of the adhesive system used.

PMID- 22402297
TI  - Polymerization degree and cementation methods of two different self-adhesive
      luting cements used for glass fiber postcementation.
AB  - AIM: Aim of this study was to evaluate two different luting cements and how their
      clinical procedures influence the postcementation quality. METHODS: Thirty-six
      freshly extracted mono-radicular teeth (N.=18) were treated endodontically and
      randomly divided into two groups. Posts were cemented respectively with two
      different self adhesive luting cements: Group A - RelyX Unicem (3M Espe) and
      Group B - Multilink Sprint (Ivoclar-Vivadent) following the manufacturers'
      instructions. Teeth were then thermocycled according to protocol ISO/TR 11405 and
      were immersed 24 hours in 2% methylene-blue solution. Each tooth was sectioned by
      a diamond-coated saw (Isomet-Buhler) from CEJ to apex. Each slice was examined
      for the presence or absence of gutta-percha remnants, voids, bubbles, dye
      infiltration degree and polymerization grade of the luting agent. Findings were
      evidenced by stereoscopic microscopy (30x) and Micro-Raman spectroscopy. Mann
      Whitney and ANOVA statistical analyses were performed for all results. RESULTS:
      No statistical significances were evidenced for gutta-percha presence, dye
      infiltration and polymerization degree. Voids were present mostly in Group B and
      bubbles in Group A. Both differences were statistically significant. CONCLUSION:
      Materials and protocols for glass fiber posts cementation are fundamental for the
      clinical success. Self adhesive luting cements, if used correctly, could be an
      acceptable and quick luting agent for postcementation.

PMID- 22402298
TI  - Efficacy of ultrasonic vibration in warm gutta-percha vertical compaction.
AB  - AIM: Vertical compaction of warm gutta-percha is a methodology to seal root
      canals and it might be associated with ultrasonic vibration. The aim of this
      paper was to determine whether vertical compaction of warm gutta-percha used with
      ultrasonic vibrations performs better compared to the traditional one. METHODS:
      Twenty-four single-rooted teeth were endodontically treated and randomly divided
      into two groups: in the first group (G1), teeth were filled using vertical
      compaction, while in the other (G2), vertical compaction was used with ultrasonic
      vibration. A microleakage test was performed after 24 h and 30 days from root
      canal sealing. RESULTS: After 24 hours, microleakage was similar in both groups
      (0.013 uL/min; SD 0.008); after 30 days, it was 0.006 uL/min (SD 0.004) in G1 and
      0.004 uL/min (SD 0.003) in G2 (P>0.05). CONCLUSION: Under these experimental
      conditions, ultrasonic vibration used with vertical compaction produced a similar
      level of sealing as the traditional method.

PMID- 22402299
TI  - Prevalence of dental anxiety and fear among five to ten year old children: a
      behaviour based cross sectional study.
AB  - AIM: Dental anxiety and fear pose a considerable challenge for the practice of
      clinical dentistry as these are problematic entities in the management of child
      patients and present a potential barrier to the utilization of oral health care
      services. The aim of this study was to estimate the prevalence of dental anxiety
      and fear among the 5-10 years aged Indian child population. METHODS: A total of
      523 children aged 5-10 years and their parents, visiting Krishna Dental College,
      Ghaziabad, India were finally recruited in this study. Dental Fear/anxiety
      distribution in the children was studied using the Indian parent's version of the
      Dental Subscale of the Children's Fear Survey Schedule (CFSS-DS). Total fear
      scores were calculated separately for boys and girls and at different age levels.
      The collected data was statistically analyzed using a SPSS statistical program.
      RESULTS: The estimated prevalence of dental anxiety among 5 to 10 year old
      children in the study population was 6.3%. The overall median CFSS-DS score was
      23 and the overall mean value of CFSS-DS score was 24. The prevalence of dental
      anxiety in children aged 5 years was 7.9%, 7.1% for 6 years old, 6.6% in 7 years
      old, 6.5% in 8 years old, 6.3% for 9 year old children and 5.8% in children aged
      10 years. No statistically significant gender differences were found in the
      dental anxiety scores. The most fear provoking situations were the sight of
      injections, the drilling procedures by the dentist, touch of a stranger and noise
      of drilling by the dentist. CONCLUSION: The results of this study indicate the
      need for preventive health education and intervention programmes in India to
      prevent and reduce dental anxiety/fear and to promote children's oral health.

PMID- 22402300
TI  - Oral mucoceles - review of the literature.
AB  - Oral mucoceles are mucin filled cavities and lined by ductal epithelium or
      covered by granulation tissue in retention or extravasation type respectively.
      The extra-vasation type is very common in the minor salivary glands (particularly
      in the labial glands), but very infrequent in the major salivary glands, whilst
      most of the retention cyst affect the major salivary glands. Partial obstruction
      of duct and spillage of mucin following trauma are the chief etiological factors.
      Though the two lesions are clinically indistinguishable, the patients are
      typically older than in the case of extra-vasation type. The case history along
      with heedful clinical examination of the lesion is crucial for diagnosing
      mucoceles correctly, but to avoid recurrences histopathological examination is
      mandatory. The surgical approach to mucoceles is the most common mode of
      treatment amongst various other techniques including cryosurgery, laser and so
      on.

PMID- 22402301
TI  - Complex roles of members of the ADP-ribosyl transferase super family in immune
      defences: looking beyond PARP1.
AB  - ADP ribosylation has been recently recognised as an important posttranslational
      modification regulating numerous cellular processes. This enzymatic activity is
      shared by two major families of enzymes, the extracellular ADP-ribosyl
      transferases, or ecto-ARTS and the poly-ADP-ribosyltranferases, whose
      denomination derives from the capacity of its founding member, PARP1, to
      synthesise large linear or branched polymers of ADP-ribose on target proteins.
      This latter post-translational modification has recently attracted much interest
      based on its role in the cellular response to genotoxic and oxidative stress.
      Accordingly, a series of PARP-specific pharmacological inhibitors have
      demonstrated cell survival and anti-inflammatory properties in vivo, promoting a
      renewed interest in the potential immunoregulatory role of this gene family. More
      recently, the role of ADP-ribosylation in regulating several aspects of
      intracellular signalling and gene transcription has been uncovered, in particular
      within cells of the immune system, revealing the potential immunomodulatory role
      of several members of this family in addition to PARP1. We review herein the
      experimental evidence illustrating the complex role played by this gene family in
      regulating multiple aspects of the immune response, including cell survival,
      cytokine gene transcription and antiviral innate defences. In particular, the
      unexpected potential anti-inflammatory role of members of this family (including
      in particular PARP5a, 5b and PARP14) will be briefly discussed, raising some
      concern on the use of pan-specific PARP inhibitors to treat chronic inflammatory
      diseases.

PMID- 22402303
TI  - Obesity trends and determinants in Indonesia.
AB  - Obesity is becoming a serious issue in many developing countries, with negative
      implications for economic growth and human wellbeing. While previous micro level
      studies on obesity have mostly used cross-section data, we analyze trends and
      determinants with panel data from Indonesia. Over the past 20 years, obesity has
      increased remarkably in Indonesia across all population groups, including rural
      and low income strata. The problem is particularly severe among women. Panel
      regressions confirm that changing food consumption patterns, coupled with
      decreasing physical activity, directly contribute to this trend. From a policy
      perspective, nutrition awareness and education campaigns, combined with programs
      to support leisure time exercise especially for women, seem to be most promising
      to contain the obesity pandemic.

PMID- 22402302
TI  - Novel fluorescent antagonist as a molecular probe in A(3) adenosine receptor
      binding assays using flow cytometry.
AB  - The physiological role of the A(3) adenosine receptor (AR) was explored in
      cardiac ischaemia, inflammatory diseases and cancer. We report a new fluorophore
      conjugated human (h) A(3)AR antagonist for application to cell-based assays in
      ligand discovery and for receptor imaging. Fluorescent pyrazolo[4,3
      e][1,2,4]triazolo[1,5-c]pyrimidin-5-ylamine (pyrazolo-triazolo-pyrimidine, PTP)
      and triazolo[1,5-c]quinazolin-5-yl)amine (triazolo-quinazoline, TQ) AR
      antagonists were compared. A chain-extended and click-conjugated Alexa Fluor-488
      TQ derivative (MRS5449) displayed a radioligand binding K(i) value of 6.4+/-2.5nM
      in hA(3)AR-expressing CHO cell membranes. MRS5449 antagonized hA(3)AR agonist
      induced inhibition of cyclic AMP accumulation in a concentration-dependent manner
      (K(B)=4.8nM). Using flow cytometry (FCM), MRS5449 saturated hA(3)ARs with very
      high specific-to-nonspecific binding ratio with an equilibrium binding constant
      5.15nM, comparable to the K(d) value of 6.65nM calculated from kinetic
      experiments. K(i) values of known AR antagonists in inhibition of MRS5449 binding
      in whole cell FCM were consistent with radioligand binding in membranes, but
      agonist binding was 5-20 fold weaker than obtained with agonist radioligand
      [(125)I]I-AB-MECA. Further binding analysis of MRS5549 suggested multiple agonist
      binding states of the A(3)AR. Molecular docking predicted binding modes of these
      fluorescent antagonists. Thus, MRS5449 is a useful tool for hA(3)AR
      characterization.

PMID- 22402304
TI  - Effects of chewing gum on the stress and work of university students.
AB  - Recent research has indicated that chewing gum can relieve perceptions of stress
      in an occupational sample (Smith, 2009). In the present study, 72 students
      completed 2 weeks of either chewing gum or refraining from chewing gum. They
      completed scales measuring perceived stress, anxiety, depression, and single item
      measures of work levels and tiredness. These were completed both pre- and post
      treatment. Perceived stress decreased as a function of the amount of gum chewed.
      The chewing gum condition was also associated with a decrease in not getting
      enough academic work done. There were no significant effects of chewing gum on
      mental health outcomes. These results confirm some of findings from previous
      studies of chewing gum and stress in other samples.

PMID- 22402305
TI  - Microdialysis--a versatile technology to perform metabolic monitoring in diabetes
      and critically ill patients.
AB  - Continuous subcutaneous glucose monitoring has been tested in type 1 diabetes
      (T1D). Since in critically ill patients vascular access is granted vascular
      microdialysis may be preferential. To test this hypothesis comparative accuracy
      data for microdialysis applied for peripheral venous and subcutaneous glucose
      monitoring was obtained in experiments in T1D patients. Twelve T1D patients were
      investigated for up to 30 h. Extracorporeal vascular (MDv) and subcutaneous
      microdialysis (MDs) was performed. Microdialysis samples were collected in 15-60
      min intervals, analyzed for glucose and calibrated to reference. MDv and MDs
      glucose levels were compared against reference. Median absolute relative
      difference was 14.0 (5.0; 28.0)% (MDv) and 9.2 (4.4; 18.4)% (MDs). Clarke Error
      Grid analysis showed that 100% (MDv) and 98.8% (MDv) were within zones A and B.
      Extracorporeal vascular and standard subcutaneous microdialysis indicated similar
      performance in T1D. We suggest microdialysis as a versatile technology for
      metabolite monitoring in subcutaneous tissue and whole blood.

PMID- 22402306
TI  - Tubular markers are associated with decline in kidney function in proteinuric
      type 2 diabetic patients.
AB  - Our aim was to investigate u-NGAL, u-KIM1 and p-FGF23 and prediction of decline
      in kidney function in type 2 diabetic patients with proteinuria. METHODS: We
      performed a follow-up study, follow-up median (range) 3.5 (1-5) years. At
      baseline u-NGAL, u-KIM1 and p-FGF23 (ELISA) was measured and patients were
      followed yearly with estimated(e)-GFR (MDRD) and u-albumin. RESULTS: We included
      177 patients (44 women), mean age (SD) 59 (9) years. eGFR 90 (24) ml/min/1.73
      m(2) at baseline, u-albumin: median (interquartile range) 104 (39-238) mg/24 h.
      Patients with levels of u-KIM1 in the highest quartile had a greater decline in
      eGFR than patients with the lowest quartile 6.0 (5.4) versus 3.2 (5.5)
      ml/min/1.73 m(2) per year (p=0.02). u-NGAL in the highest versus lowest quartile
      eGFR decline: 5.1 (4.7) and 2.8 (7.1)ml/min/1.73 m(2) per year (p=0.07). Higher
      values of u-NGAL and u-KIM1 were associated with enhanced decline in eGFR (R=0.16
      and R=0.19, p<0.05), however not after adjustment for progression promoters. p
      FGF23 was not predictive of decline in eGFR. CONCLUSION: Higher levels of markers
      of tubular damage are associated with a faster decline in eGFR. However, since
      this is not independent of known progression promoters, measurement of tubular
      markers does not give additional prognostic information.

PMID- 22402307
TI  - BRCA1 promoter methylation in peripheral blood DNA was identified in sporadic
      breast cancer and controls.
AB  - OBJECTIVE: Epigenetics, particularly DNA methylation, has recently been shown to
      be important in breast cancer initiation. We investigated the clinical and
      prognostic importance of whole blood breast cancer early onset gene 1 (BRCA1) DNA
      methylation in sporadic breast cancer. METHODS: Genomic DNA was extracted from
      the peripheral blood cells (PBCs) of 902 breast cancer patients at diagnosis,
      with no BRCA1 mutation, and 990 control women. DNA methylation was measured by
      quantitative analysis of methylated alleles (QAMA) to estimate the extent of
      methylation of 2 CpG sites in the promoter region of BRCA1 oncosuppressor.
      RESULTS: BRCA1 promoter methylation rate in PBCs was 47.1% with a 95% confidence
      interval [46.1; 48.1] in breast cancer patients, and 45.9% with a 95% confidence
      interval [45.0; 46.8] in controls. We found a trend toward BRCA1 promoter
      hypermethylation in PBCs of sporadic breast cancer patients compared with
      controls. Association between methylation and clinicopathological features was
      evaluated using statistical tests. BRCA1 promoter methylation in PBCs increased
      significantly in breast cancer patients compared with controls, for age over 70
      years (p=0.022), in post-menopausal status (p=0.013), for a body mass index (BMI)
      <20 (p=0.0095) or a waist-to-hip ratio (WHR) <=76.8 (p=0.0027). We also found an
      association of increased BRCA1 promoter methylation in PBCs with ACA/ACA genotype
      for the SNP Thr594Thr in ESR (estrogen receptor gene), known to be associated
      with breast cancer risk (p=0.092), reflecting the reduced presence of this
      genotype in this breast cancer case-control study. CONCLUSION: Analysis of site
      specific DNA methylation in PBCs by QAMA provides quantitative DNA methylation
      values that may serve as important prognostic indicators.

PMID- 22402308
TI  - The association between UGT1A7 polymorphism and cancer risk: a meta-analysis.
AB  - BACKGROUND: studies investigating the associations between UDP
      glucuronosyltransferase 1A7 (UGT1A7) gene polymorphisms and various carcinomas
      risk reported conflicting results. To derive a more precise estimation of the
      association, we have conducted a meta-analysis. METHODS: data were collected from
      the following electronic databases: PubMed, Medline and Chinese Biomedical
      Literature Database, with the last report up to September 2011. Case-control
      studies containing available genotype frequencies of UGT1A7 were chose. The odds
      ratio (OR) and its 95% confidence interval (95%CI) were used to assess the
      strength of association. RESULTS: a total of 22 separate case-control studies
      including 3852 cases and 5604 controls based on the search criteria were involved
      in this meta-analysis. The combined results based on all studies showed that
      there was a statistically significant link between UGT1A7*3 allele and cancer
      risk (OR = 1.31, 95%CI = 1.14-1.50, P = 0.0001). In the stratified analysis by
      racial descent, significant increased risk was found in Asian population for
      UGT1A7*3 allele (OR = 1.41, 95%CI = 1.22-1.63, P < 0.00001). No significant
      associations were found between the UGT1A7 polymorphism and cancer susceptibility
      among Caucasians and African-Americans. In the subgroup analysis by cancer types,
      significant associations were found in UGT1A7*2 allele (OR = 1.23, 95%CI = 1.06
      1.43, P = 0.006) and *3 allele (OR = 1.51, 95%CI = 1.11-2.06, P = 0.009) for
      hepatocellular carcinoma, *3 allele for lung cancer (OR = 1.36, 95%CI = 1.11
      1.68, P = 0.004) and for bladder cancer (OR = 1.50, 95%CI = 1.09-2.07, P = 0.01).
      CONCLUSIONS: This meta-analysis suggests that the UGT1A7*3 allele is a risk
      factor for cancer among Asians, especially for hepatocellular carcinoma.

PMID- 22402309
TI  - Fragrance material review on 3-phenyl-3-buten-1-yl acetate.
AB  - A toxicologic and dermatologic review of 3-phenyl-3-buten-1-yl acetate when used
      as a fragrance ingredient is presented. 3-Phenyl-3-buten-1-yl acetate is a member
      of the fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE).
      The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol
      with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate,
      acetate, propionate, butyrate, isobutyrate and carbonate esters. This review
      contains a detailed summary of all available toxicology and dermatology papers
      that are related to this individual fragrance ingredient and is not intended as a
      stand-alone document. Available data for 3-phenyl-3-buten-1-yl acetate were
      evaluated, then summarized, and includes: physical properties, acute toxicity,
      skin irritation, mucous membrane (eye) irritation, and skin sensitization data. A
      safety assessment of the entire AAASAE will be published simultaneously with this
      document. Please refer to Belsito et al. (2012) for an overall assessment of the
      safe use of this material and all AAASAE in fragrances.

PMID- 22402310
TI  - Fragrance material review on 2-methyl-4-phenyl-2-butyl acetate.
AB  - A toxicologic and dermatologic review of 2-methyl-4-phenyl-2-butyl acetate when
      used as a fragrance ingredient is presented. 2-Methyl-4-phenyl-2-butyl acetate is
      a member of the fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters
      (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl
      alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate
      formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This
      review contains a detailed summary of all available toxicology and dermatology
      papers that are related to this individual fragrance ingredient and is not
      intended as a stand-alone document. Available data for 2-methyl-4-phenyl-2-butyl
      acetate were evaluated then summarized and includes physical properties, acute
      toxicity, skin irritation, skin sensitization, and elicitation data. A safety
      assessment of the entire AAASAE will be published simultaneously with this
      document. Please refer to Belsito et al. (2012) for an overall assessment of the
      safe use of this material and all AAASAE in fragrances.

PMID- 22402311
TI  - Characterization of melamine-associated urinary stones in children with
      consumption of melamine-contaminated infant formula.
AB  - BACKGROUND: Crystalline morphology and compositions of melamine-associated
      urinary stones caused by consumption of melamine-contaminated infant formula are
      reported. METHODS: Twelve melamine-associated urinary stone samples were obtained
      from 12 children aged from 3 to 36 months who were treated in Lanzhou University
      Second Hospital. The crystalline morphology and compositions of these stone
      samples were analyzed using a combination of infrared spectrum, SEM and XRD. The
      presence of melamine in 12 stones was determined by HPLC. RESULTS: Diversity of
      crystalline morphology in 10 stone samples was revealed by SEM observation.
      Infrared spectral data revealed that 8 of the 10 stone samples predominantly
      consisted of the crystal forms of urate: 1 of sodium urate monohydrate, 2 of
      uricite and 5 of uric acid dihydrate and ammonium urate. However, ammonium
      magnesium phosphate hexahydrate, ammonium urate and carbonate apatite were also
      identified in 1 stone sample. The content of melamine in all of the 12 stone
      samples was determined by HPLC and found to range from 200 to 339,000 MUg/g. XRD
      analysis in 6 stone samples showed that amorphous mineral phase was involved in
      the calculogenesis. CONCLUSIONS: Melamine and uric acid are the main possible
      etiologic factors closely related to melamine-associated urinary stone formation
      in humans.

PMID- 22402312
TI  - Simultaneous determination of tyrosine, tryptophan and 5-hydroxytryptamine in
      serum of MDD patients by high performance liquid chromatography with fluorescence
      detection.
AB  - BACKGROUND: Tyrosine (Tyr), Tryptophan (Trp) and 5-hydroxytryptamine (5-HT) are
      important amino acids in vivo and have been hypothesized to be involved in many
      mental disorders. We developed a rapid and sensitive HPLC method for simultaneous
      measurement of serum Tyr, Trp and 5-HT and explored the clinical significances of
      Tyr, Trp and 5-HT and the 5-HT/Trp ratio for patients with major depressive
      disorder (MDD) disease. METHODS: Serum samples were deproteinized by 5%
      perchloric acid and separated on an Atlantis C18 column (4.6 * 150 mm, 5 MUm)
      with the mobile phase consisting of 0.1 mol/l KH(2)PO(4) and methanol (85:15,
      V/V).The eluates were monitored by the fluorescence detection with programmed
      wavelength. RESULTS: Analysis was achieved in <12.0 min. The limits of
      quantification were 0.014, 0.005, and 0.024 MUmol/l for Tyr, Trp and 5-HT,
      respectively. Reproducibility and recovery were satisfactory. Tyr, Trp and 5-HT
      and the 5-HT/Trp ratio were significantly decreased in patients with MDD.
      CONCLUSIONS: In diseases, like MDD, Tyr, Trp and 5-HT play an important role.
      This method can potentially be applied as prognostic or diagnostic tool or even
      to follow the evolution of the illness or of the treatment.

PMID- 22402313
TI  - Which is access suitable for a solitary upper pole renal stone? A possible novel
      criterion.
AB  - AIM: The aim of the present study was to discover a new criterion for choosing
      subcostal or supracostal upper pole renal access before performing PCNL in upper
      pole renal stone cases. METHODS: Between April 2006 and July 2009 we performed 35
      subcostal upper poles PCNL in solitary upper pole stone cases. The inclusion
      criteria were stone size >1.5 cm or stone size <1.5 cm and resistant to
      extracorporeal shockwave lithotripsy. The exclusion criteria were renal
      anomalies, uretero-pelvic junction obstruction, multiple stone (associated pelvic
      or a lower pole stone) and any contraindication for surgery. We determined access
      length as the new criterion (the distance between the point of needle entrance
      and lower border of stone on the skin) and access success, in all patients. Then
      we analyzed the relationship between these two main variables and used roc curve
      to find a reliable cut point of access length. RESULTS: The mean of access length
      was 9.72 cm (range: 6-14) and access was successful in 29 (82.8%) patients.
      Between measured variables, access length was the only variable that related to
      access success (P=0.04); furthermore, two reliable cut points (8 cm and 12 cm)
      for predicting access success. If access length was <8 cm or 8-12 cm or >12 cm,
      the access success was 100%, 83% and 50%, respectively. CONCLUSION: Access length
      can be used as a criterion for choosing subcostal upper pole renal PCNL and
      predicting its success, in the case of solitary upper pole renal stones 12 cm can
      serve as a critical valve for a decision.

PMID- 22402314
TI  - Molecular signaling and the role of targeted therapies in bladder cancer.
AB  - Through our growing understanding of the molecular mechanisms that drive
      urothelial transformation and the growth, invasion and metastasis of bladder
      cancer, we are able to identify an increasingly broad spectrum of molecules and
      pathways that are suitable for novel targeted therapies. At the same time we are
      armed with an increasing number of agents designed to disrupt these signaling
      pathways, and, as these enter the clinical arena in other cancers, the barriers
      to use in bladder cancer patients decline. Targeted therapy for bladder cancer,
      however, remains in its infancy, and no major breakthroughs have been achieved.
      Here we review some of the molecular targets that have been best characterized in
      bladder cancer, as well as some of the newer targets that appear most promising.
      We will review the experience up to this point in testing targeted agents against
      these pathways, and describe some novel agents that have yet to be tested in
      clinical trials but have shown significant potential in pre-clinical models.

PMID- 22402316
TI  - Androgen action in the prostate gland.
AB  - The embryonic development, growth and maturation of the prostate relies on
      androgens, the male sex steroids, acting through their cognate receptor, the
      androgen receptor (AR). This dependence on androgens continues in adult life,
      where AR signaling remains necessary for the maintenance of the structural and
      functional integrity of the prostate gland. Moreover, AR action contributes to
      the development and progression of prostate cancer (PCa), which is the most
      common malignancy in Western men. Androgen deprivation therapies (ADTs) that
      interfere with ligand activation of AR to prevent expression of AR target genes
      and androgen action on target cells have been the standard therapy for locally
      advanced or recurrent PCa for 7 decades. While they initially induce remission,
      ADTs are not curative and eventually PCa recurs as castration-recurrent (CR)
      disease, which is invariably lethal. Despite low levels of circulating androgens,
      CR PCa cell proliferation still relies on a functional AR. Recently, new insights
      into the cellular processes and determinants that regulate AR action, including
      intraprostatic androgen metabolism, AR structure and function, a novel role for
      well-known tumor suppressors and oncogenes in the control of AR transcriptional
      output, unexpected non-transcriptional roles for AR, and the identification of
      distinct modes of androgen-dependent gene expression, have enhanced markedly our
      understanding of the AR-dependent events that contribute to progression to the
      lethal stage of PCa. Here, we provide a general overview of androgen action in
      prostate (cancer), summarize these novel concepts in AR action and discuss their
      implications for the optimization of therapeutic intervention in PCa.

PMID- 22402317
TI  - Drugs and AKI.
AB  - Acute kidney injury is a common complication in hospitalized patients and is
      associated with substantially increased morbidity and mortality. Frequently, it
      is caused by impaired renal perfusion, ischemia and reperfusion injury, sepsis or
      urinary tract obstruction, but often its etiology is multifactorial. In this
      context, the contribution of nephrotoxic medications to the development of AKI
      plays an important role. This review begins with an attempt to evaluate the
      importance of drug-related acute kidney injury in general. Then, a selected list
      of 7 classes of drugs or compounds, namely aminoglycosides, aristolochic acid,
      cytostatic drugs, nonsteroidal anti-inflammatory drugs, osmotic agents,
      radiocontrast, and phosphate salts are discussed in depth, including their
      epidemiology, pathophysiology, clinical features and treatment. While not
      attempting to be exhaustive, this review attempts to provide an overview with
      additional in-depth information on certain classes of drugs that are either of
      general importance or have recently emerged in the literature.

PMID- 22402315
TI  - Prostate cancer stem cell biology.
AB  - The cancer stem cell (CSC) model provides insights into pathophysiology of
      cancers and their therapeutic response. The CSC model has been both
      controversial, yet provides a foundation to explore cancer biology. In this
      review, we provide an overview of CSC concepts, biology and potential therapeutic
      avenues. We then focus on prostate CSC including 1) their purported origin as
      either basal-derived or luminal-derived cells; 2) markers used for prostate CSC
      identification; 3) alterations of signaling pathways in prostate CSCs; 4)
      involvement of prostate CSCs in metastasis of PCa; and 5) microRNA-mediated
      regulation of prostate CSCs. Although definitive evidence for the identification
      and characterization of prostate CSCs still remains unclear, future directions
      pursuing therapeutic targets of CSCs may provide novel insights for the treatment
      of PCa.

PMID- 22402318
TI  - Pathogenesis and management of renovascular hypertension and ischemic
      nephropathy.
AB  - Renovascular disease is an important cause of secondary hypertension and renal
      impairment. Atherosclerotic renal artery stenosis (ARAS) is the most important
      cause of renal artery stenosis (RAS), and has been linked to increased
      cardiovascular risk. The pathogenesis of renovascular hypertension is complex,
      but is mainly due to the over-activation of Renin-Angiotensin-Aldosterone system.
      A major consequence of untreated RAS is ischemic nephropathy, which is due to the
      sustained reduction in renal perfusion leading to derangement of microvascular
      function, and eventual development of interstitial fibrosis. Diagnosis of these
      conditions can be complex, sometimes needing invasive testing. Aggressive medical
      management is key to preventing progression of disease, as the role of
      revascularization in the management of ARAS is still not well defined.

PMID- 22402319
TI  - Effect of herpes simplex virus vector-mediated interleukin-4 gene therapy on
      bladder overactivity and nociception.
AB  - We investigated the effects of replication-defective herpes simplex virus (HSV)
      vector expression of interleukin-4 (IL-4) on bladder overactivity and
      nociception. HSV vector expressing murine interleukin-4 (S4IL4) or the control
      vector expressing beta-galactosidase (SHZ) were injected to the rat bladder wall.
      At 1 week after viral injection, in cystometry performed under urethane
      anesthesia, the S4IL4-treated group did not show the intercontraction intervals
      reduction during intravesical administration of 10 nM resiniferatoxin (RTx). At 2
      weeks after viral injection, behavioral studies were performed on vector-injected
      animals in an awakened state. Freezing behavior induced by 3 MUM RTx,
      administered for 1 min into the bladder, was significantly suppressed in the
      S4IL4 group compared with the SHZ group. Murine IL-4 levels examined by ELISA
      were significantly increased in bladder and bladder afferent dorsal root ganglia
      at 2 weeks after viral injection. The expression of IL-1beta and IL-2 and bladder
      inflammatory responses were significantly suppressed in the RTx-irritated bladder
      of S4IL4-injected rats. These results indicate that HSV vector-mediated
      interleukin-4 expression in the bladder and bladder afferent pathways reduces the
      inflammatory response, bladder overactivity and nociceptive behavior induced by
      bladder irritation in the rat model. Therefore, IL-4 gene therapy could be a new
      strategy for treating urinary frequency and/or bladder pain.

PMID- 22402321
TI  - A reporter system for replication-competent gammaretroviruses: the inGluc-MLV
      DERSE assay.
AB  - Although novel retroviral vectors for use in gene-therapy products are reducing
      the potential for formation of replication-competent retrovirus (RCR), it remains
      crucial to screen products for RCR for both research and clinical purposes. For
      clinical-grade gammaretrovirus-based vectors, RCR screening is achieved by an
      extended S(+)L(-) or marker-rescue assay, whereas standard methods for
      replication-competent lentivirus detection are still in development. In this
      report, we describe a rapid and sensitive method for replication-competent
      gammaretrovirus detection. We used this assay to detect three members of the
      gammaretrovirus family and compared the sensitivity of our assay with well
      established methods for retrovirus detection, including the extended S(+)L(-)
      assay. Results presented here demonstrate that this assay should be useful for
      gene-therapy product testing.

PMID- 22402320
TI  - Three-dimensional multipotent progenitor cell aggregates for expansion,
      osteogenic differentiation and 'in vivo' tracing with AAV vector serotype 6.
AB  - Multipotent adult progenitor cells (MAPCs) are bone marrow-derived stem cells
      with a high growth rate suitable for therapeutical applications as three
      dimensional (3D) aggregates. Combined applications of osteogenically
      differentiated MAPC (OD-MAPC) aggregates and adeno-associated viral vectors (AAV)
      in bone bioengineering are still deferred until information with regard to
      expansion technologies, osteogenic potential, and AAV cytotoxicity and
      transduction efficiency is better understood. In this study, we tested whether
      self-complementary AAV (scAAV) can potentially be used as a gene delivery system
      in an OD-MAPC-based 'in vivo' bone formation model in the craniofacial region.
      Both expansion of rat MAPC (rMAPC) and osteogenic differentiation with
      dexamethasone were also tested in 3D aggregate culture systems 'in vitro' and
      'vivo'. rMAPCs grew as undifferentiated aggregates for 4 days, with a population
      doubling time of 37 h. After expansion, constant levels of Oct4 transcripts, and
      Oct4 and CD31 surface markers were observed, which constitute a hallmark of
      undifferentiated stage of rMAPCs. Dexamethasone effectively mediated rMAPC
      osteogenic differentiation by inducing the formation of a mineralized collagen
      type I network, and facilitated the activation of the wnt/beta-catenin, a crucial
      pathway in skeletal development. To investigate the genetic modification of
      rMAPCs grown as 3D aggregates before implantation, scAAV serotypes 2, 3 and 6
      were evaluated. scAAV6 packaged with the enhanced green fluorescent protein
      expression cassette efficiently mediated long-term transduction (10 days) 'in
      vitro' and 'vivo'. The reporter transduction event allowed the tracing of OD
      rMAPC (induced by dexamethasone) aggregates following OD-rMAPC transfer into a
      macro-porous hydroxyapatite scaffold implanted in a rat calvaria model.
      Furthermore, the scAAV6-transduced OD-rMAPCs generated a bone-like matrix with a
      collagenous matrix rich in bone-specific proteins (osteocalcin and osteopontin)
      in the scaffold macro-pores 10 days post-implantation. Newly formed bone was also
      observed in the interface between native bone and scaffold. The collective work
      supports future bone tissue engineering applications of 3D MAPC cultures for
      expansion, bone formation and the ability to alter genetically these cells using
      scAAV vectors.

PMID- 22402323
TI  - Directed evolution of novel adeno-associated viruses for therapeutic gene
      delivery.
AB  - Gene therapy vectors based on adeno-associated virus (AAV) are currently in
      clinical trials for numerous disease targets, such as muscular dystrophy,
      hemophilia, Parkinson's disease, Leber's congenital amaurosis and macular
      degeneration. Despite its considerable promise and emerging clinical success,
      several challenges impede the broader implementation of AAV gene therapy,
      including the prevalence of neutralizing antibodies in the human population, low
      transduction of a number of therapeutically relevant cell and tissue types, an
      inability to overcome physical and cellular barriers in vivo and a relatively
      limited carrying capacity. These challenges arise as the demands we place on AAV
      vectors are often different from or even at odds with the properties nature
      bestowed on their parent viruses. Viral-directed evolution-the iterative
      generation of large, diverse libraries of viral mutants and selection for
      variants with specific properties of interest-offers an approach to address these
      problems. Here we outline progress in creating novel classes of AAV variant
      libraries and highlight the successful isolation of variants with novel and
      advantageous in vitro and in vivo gene delivery properties.

PMID- 22402322
TI  - Neural stem cell-mediated CE/CPT-11 enzyme/prodrug therapy in transgenic mouse
      model of intracerebellar medulloblastoma.
AB  - Medulloblastoma is a heterogeneous diffuse neoplasm that can be highly
      disseminated, and is the most common malignant childhood brain tumor. Although
      multimodal treatments have improved survival rates for patients with
      medulloblastoma, these tumors are associated with high morbidity and mortality.
      New treatment strategies are urgently needed to improve cure rates and,
      importantly, to spare normal brain tissue from neurotoxicity and patients from
      life-long cognitive and functional deficits associated with current therapies. In
      numerous preclinical brain tumor models, neural stem cells (NSCs) have shown
      great promise as delivery vehicles for therapeutic genes. Here, we have used an
      established, genetically modified human NSC line (HB1.F3.CD) to deliver
      carboxylesterase (CE) to cerebellar tumor foci and locally activate the prodrug
      camptothecin-11 (CPT-11) (Irinotecan) to the potent topoisomerase I inhibitor SN
      38. HB1.F3.CD NSC tumor tropism, intratumoral distribution and therapeutic
      efficacy were investigated in clinically relevant experimental models. Magnetic
      resonance imaging was used for in vivo tracking of iron nanoparticle-labeled
      NSCs, and to assess the therapeutic efficacy of CE-expressing HB1.F3.CD cells. As
      compared with controls, a significant decrease in tumor growth rate was seen in
      mice that received both NSCs and CPT-11 as their treatment regimen. Thus, this
      study provides proof-of-concept for NSC-mediated CE/CPT-11 treatment of
      medulloblastoma, and serves as a foundation for further studies toward potential
      clinical application.

PMID- 22402324
TI  - Butyrylcholinesterase genotype and gender influence Alzheimer's disease
      phenotype.
AB  - Retrospective data are presented to support a spectrum of early Alzheimer's
      disease (AD) along a continuum defined by gender and genotype. The putative
      neurodegenerative mechanisms driving distinct phenotypes at each end of the
      spectrum are glial hypoactivity associated with early failure of synaptic
      cholinergic neurotransmission and glial overactivation associated with loss of
      neural network connectivity due to accelerated age-related breakdown of myelin.
      In early AD, male butyrylcholinesterase K-variant carriers with one or two
      apolipoprotein E4 alleles have prominent medial temporal atrophy, synaptic
      failure, cognitive decline, and accumulation of aggregated beta-amyloid peptide.
      Increasing synaptic acetylcholine in damaged but still functional cholinergic
      synapses improves cognitive symptoms, whereas increasing the ability of glia to
      support synapses and to clear beta-amyloid peptide might be disease-modifying.
      Conversely, chronic glial overactivation can also drive degenerative processes
      and in butyrylcholinesterase K-variant negative females generalized glial
      overactivation may be the main driver from mild cognitive impairment to AD.
      Females are more likely than males to have accelerated age-related myelin
      breakdown, more widespread white matter loss, loss of neural network
      connectivity, whole brain atrophy, and functional decline. Increasing
      extracellular acetylcholine levels blocks glial activation, reduces myelin loss
      and damage to neural network connectivity, and is disease-modifying. Between
      extremes characterized by gender, genotype, and age, pathophysiology may be mixed
      and this spectrum may explain much of the heterogeneity of amnestic mild
      cognitive impairment. Preservation of the functional integrity of the neural
      network may be an important component of strengthening cognitive reserve and
      significantly delaying the onset and progression of dementia, particularly in
      females. Prospective confirmation of these hypotheses is required. Implications
      for future research and therapeutic opportunities are discussed.

PMID- 22402325
TI  - Application of growing hierarchical SOM for visualisation of network forensics
      traffic data.
AB  - Digital investigation methods are becoming more and more important due to the
      proliferation of digital crimes and crimes involving digital evidence. Network
      forensics is a research area that gathers evidence by collecting and analysing
      network traffic data logs. This analysis can be a difficult process, especially
      because of the high variability of these attacks and large amount of data.
      Therefore, software tools that can help with these digital investigations are in
      great demand. In this paper, a novel approach to analysing and visualising
      network traffic data based on growing hierarchical self-organising maps (GHSOM)
      is presented. The self-organising map (SOM) has been shown to be successful for
      the analysis of highly-dimensional input data in data mining applications as well
      as for data visualisation in a more intuitive and understandable manner. However,
      the SOM has some problems related to its static topology and its inability to
      represent hierarchical relationships in the input data. The GHSOM tries to
      overcome these limitations by generating a hierarchical architecture that is
      automatically determined according to the input data and reflects the inherent
      hierarchical relationships among them. Moreover, the proposed GHSOM has been
      modified to correctly treat the qualitative features that are present in the
      traffic data in addition to the quantitative features. Experimental results show
      that this approach can be very useful for a better understanding of network
      traffic data, making it easier to search for evidence of attacks or anomalous
      behaviour in a network environment.

PMID- 22402326
TI  - Simulating the effects of dopamine imbalance on cognition: from positive affect
      to Parkinson's disease.
AB  - Cools (2006) suggested that prefrontal dopamine levels are related to cognitive
      stability whereas striatal dopamine levels are related to cognitive plasticity.
      With such a wide ranging role, almost all cognitive activities should be affected
      by dopamine levels in the brain. Not surprisingly, factors influencing brain
      dopamine levels have been shown to improve/worsen performance in many behavioral
      experiments. On the one hand, Nadler, Rabi, and Minda (2010) showed that positive
      affect (which is thought to increase cortical dopamine levels) improves a type of
      categorization that depends on explicit reasoning (rule-based) but not another
      type that depends on procedural learning (information-integration). On the other
      hand, Parkinson's disease (which is known to decrease dopamine levels in both the
      striatum and cortex) produces proactive interference in the odd-man-out task
      (Flowers & Robertson, 1985) and renders subjects insensitive to negative feedback
      during reversal learning (Cools, Altamirano, & D'Esposito, 2006). This article
      uses the COVIS model of categorization to simulate the effects of different
      dopamine levels in categorization, reversal learning, and the odd-man-out task.
      The results show a good match between the simulated and human data, which
      suggests that the role of dopamine in COVIS can account for several cognitive
      enhancements and deficits related to dopamine levels in healthy and patient
      populations.

PMID- 22402327
TI  - Specific antibody titer alters the effectiveness of intrathecal enzyme
      replacement therapy in canine mucopolysaccharidosis I.
AB  - Intrathecal enzyme replacement therapy is an experimental option to treat central
      nervous system disease due to lysosomal storage. Previous work shows that MPS I
      dogs receiving enzyme replacement with recombinant human alpha-l-iduronidase into
      the cisterna magna showed normal brain glycosaminoglycan (GAG) storage after
      three or four doses. We analyzed MPS I dogs that received intrathecal enzyme in a
      previous study using an assay that detects only pathologic GAG (pGAG). To
      quantify pGAG in MPS I, the assay measures only those GAG which display terminal
      iduronic acid residues on their non-reducing ends. Mean cortical brain pGAG in
      six untreated MPS I dogs was 60.9+/-5.93 pmol/mg wet weight, and was 3.83+/-2.64
      in eight normal or unaffected carrier animals (p<0.001). Intrathecal enzyme
      replacement significantly reduced pGAG storage in all treated animals. Dogs with
      low anti-iduronidase antibody titers showed normalization or near-normalization
      of pGAG in the brain (mean 8.17+/-6.17, n=7), while in dogs with higher titers,
      pGAG was reduced but not normal (mean 21.9+/-6.02, n=4). Intrathecal enzyme
      therapy also led to a mean 69% reduction in cerebrospinal fluid pGAG (from 83.8+/
      26.3 to 27.2+/-12.3 pmol/ml CSF). The effect was measurable one month after each
      dose and did not differ with antibody titer. Prevention of the immune response to
      enzyme may improve the efficacy of intrathecal enzyme replacement therapy for
      brain disease due to MPS I.

PMID- 22402328
TI  - Lysinuric protein intolerance (LPI): a multi organ disease by far more complex
      than a classic urea cycle disorder.
AB  - Lysinuric protein intolerance (LPI) is an inherited defect of cationic amino acid
      (lysine, arginine and ornithine) transport at the basolateral membrane of
      intestinal and renal tubular cells caused by mutations in SLC7A7 encoding the
      y(+)LAT1 protein. LPI has long been considered a relatively benign urea cycle
      disease, when appropriately treated with low-protein diet and l-citrulline
      supplementation. However, the severe clinical course of this disorder suggests
      that LPI should be regarded as a severe multisystem disease with uncertain
      outcome. Specifically, immune dysfunction potentially attributable to nitric
      oxide (NO) overproduction secondary to arginine intracellular trapping (due to
      defective efflux from the cell) might be a crucial pathophysiological route
      explaining many of LPI complications. The latter comprise severe lung disease
      with pulmonary alveolar proteinosis, renal disease, hemophagocytic
      lymphohistiocytosis with subsequent activation of macrophages, various auto
      immune disorders and an incompletely characterized immune deficiency. These
      results have several therapeutic implications, among which lowering the l
      citrulline dosage may be crucial, as excessive citrulline may worsen
      intracellular arginine accumulation.

PMID- 22402329
TI  - Changes in serum cortisol levels during community-acquired pneumonia: the
      influence of dexamethasone.
AB  - In community-acquired pneumonia (CAP), the cortisol level on admission can be a
      useful biomarker for prognosis. Serial cortisol measurements during the clinical
      course of disease and their association with disease outcome have never been
      reported. Furthermore, the time to recovery of the hypothalamic-pituitary-adrenal
      axis after a short course of dexamethasone during infection is unclear. We
      analyzed data from 270 hospitalized patients with CAP. Total serum cortisol was
      measured on presentation, day 1, 2, 4, and on control visit (day 30). Intensive
      care unit (ICU) admission and mortality were assessed. Additionally, to study the
      influence of dexamethasone on the kinetics of the cortisol response, we analyzed
      serial cortisol values of 43 patients treated with a four-day regimen of
      dexamethasone 5 mg. During hospital stay, 26/270 patients (9.6%) were admitted to
      the ICU and 15/270 patients (5.6%) died. Compared to patients with an uneventful
      recovery, cortisol on presentation was significantly higher in patients with an
      adverse outcome (360 MUg/L, IQR 209-597 vs. 238 MUg/L, IQR 151-374) (p:0.01), and
      also remained significantly higher throughout the course of disease.
      Dexamethasone treatment resulted in nearly complete suppression of the endogenous
      cortisol production after the first dose, but cortisol production was fully
      recovered on control visit. In conclusion, we showed that an adverse outcome of
      CAP was associated with persisting higher total serum cortisol throughout the
      course of disease. Delta-cortisol could be another meaningful biomarker in CAP.
      Next, our data indicate that a four-day dexamethasone regimen during CAP does not
      lead to prolonged secondary adrenal insufficiency.

PMID- 22402330
TI  - Effect of gender, cadence, and water immersion on ground reaction forces during
      stationary running.
AB  - STUDY DESIGN: Controlled laboratory study. OBJECTIVES: To analyze the vertical
      and anteroposterior components of the ground reaction force during stationary
      running performed in water and on dry land, focusing on the effect of gender,
      level of immersion, and cadence. BACKGROUND: Stationary running, as a fundamental
      component of aquatic rehabilitation and training protocols, is little explored in
      the literature with regard to biomechanical variables, which makes it difficult
      to determine and control the mechanical load acting on the individuals. METHODS:
      Twenty-two subjects performed 1 minute of stationary running on land, immersed to
      the hip, and immersed to the chest at 3 different cadences: 90 steps per minute,
      110 steps per minute, and 130 steps per minute. Force data were acquired with a
      force plate, and the variables were vertical peak (Fy), loading rate (LR),
      anterior peak (Fx anterior), and posterior peak (Fx posterior). Data were
      normalized to subjects' body weight (BW) and analyzed using repeated-measures
      analysis of variance. RESULTS: Fy ranged from 0.98 to 2.11 BW, LR ranged from
      5.38 to 11.52 BW/s, Fx anterior ranged from 0.07 to 0.14 BW, and Fx posterior
      ranged from 0.06 to 0.09 BW. The gender factor had no effect on the variables
      analyzed. A significant interaction between level of immersion and cadence was
      observed for Fy, Fx anterior, and Fx posterior. On dry land, Fy increased with
      increasing cadence, whereas in water this effect was seen only between 90 steps
      per minute and the 2 higher cadences. The higher the level of immersion, the
      lower the magnitude of Fy. LR was reduced under both water conditions and
      increased with increasing cadence, regardless of the level of immersion.
      CONCLUSION: Ground reaction forces during stationary running are similar between
      genders. Fy and LR are lower in water, though the values are increased at higher
      cadences.

PMID- 22402331
TI  - Disrupted GABAAR trafficking and synaptic inhibition in a mouse model of
      Huntington's disease.
AB  - Growing evidence suggests that Huntington's disease (HD), a neurodegenerative
      movement disorder caused by the mutant huntingtin (htt) with an expanded
      polyglutamine (polyQ) repeat, is associated with the altered intracellular
      trafficking and synaptic function. GABA(A) receptors, the key determinant of the
      strength of synaptic inhibition, have been found to bind to the huntingtin
      associated protein 1 (HAP1). HAP1 serves as an adaptor linking GABA(A) receptors
      to the kinesin family motor protein 5 (KIF5), controlling the transport of
      GABA(A) receptors along microtubules in dendrites. In this study, we found that
      GABA(A)R-mediated synaptic transmission is significantly impaired in a transgenic
      mouse model of HD expressing polyQ-htt, which is accompanied by the diminished
      surface expression of GABA(A) receptors. Moreover, the GABA(A)R/HAP1/KIF5 complex
      is disrupted and dissociated from microtubules in the HD mouse model. These
      results suggest that GABA(A)R trafficking and function is impaired in HD,
      presumably due to the interference of KIF5-mediated microtubule-based transport
      of GABA(A) receptors. The diminished inhibitory synaptic efficacy could
      contribute to the loss of the excitatory/inhibitory balance, leading to increased
      neuronal excitotoxicity in HD.

PMID- 22402332
TI  - c-Jun-dependent sulfiredoxin induction mediates BDNF protection against
      mitochondrial inhibition in rat cortical neurons.
AB  - In current study, we tested the hypothesis that c-Jun-dependent sulfiredoxin
      expression mediates protective effects of brain-derived neurotrophic factor
      (BDNF) against neurotoxicity induced by 3-nitropropionic acid (3-NP), a
      mitochondrial complex II inhibitor, in primary rat cortical cultures. We found
      that BDNF-dependent c-Jun expression and nuclear translocation required prior
      phosphorylation of extracellular signal-regulated kinase (ERK)1/2, but not Akt.
      BDNF also transiently activated the expression of sulfiredoxin, an ATP-dependent
      antioxidant enzyme, at both mRNA and protein levels. Furthermore, both c-Jun
      siRNA and ERK1/2 inhibitor PD98059 suppressed BDNF-induced sulfiredoxin
      expression. Finally, PD98059, c-Jun siRNA, and sulfiredoxin siRNA all abrogated
      BDNF-mediated 3-NP resistance. Together, these results established a signaling
      cascade of "BDNF -> ERK1/2-Pi -> c-Jun -> sulfiredoxin -> 3-NP resistance". We
      therefore conclude that c-Jun-induced sulfiredoxin mediates the BDNF-dependent
      neuroprotective effects against 3-NP toxicity in primary rat cortical neurons, at
      least in part.

PMID- 22402333
TI  - Age-related functional and structural retinal modifications in the Igf1-/- null
      mouse.
AB  - BACKGROUND: Mutations in the gene encoding human insulin-like growth factor-I
      (IGF-I) cause syndromic neurosensorial deafness. To understand the precise role
      of IGF-I in retinal physiology, we have studied the morphology and
      electrophysiology of the retina of the Igf1(-/-) mice in comparison with that of
      the Igf1(+/-) and Igf1(+/+) animals during aging. METHODS: Serological
      concentrations of IGF-I, glycemia and body weight were determined in Igf1(+/+),
      Igf1(+/-) and Igf1(-/-) mice at different times up to 360days of age. We have
      analyzed hearing by recording the auditory brainstem responses (ABR), the retinal
      function by electroretinographic (ERG) responses and the retinal morphology by
      immunohistochemical labeling on retinal preparations at different ages. RESULTS:
      IGF-I levels are gradually reduced with aging in the mouse. Deaf Igf1(-/-) mice
      had an almost flat scotopic ERG response and a photopic ERG response of very
      small amplitude at postnatal age 360days (P360). At the same age, Igf1(+/-) mice
      still showed both scotopic and photopic ERG responses, but a significant decrease
      in the ERG wave amplitudes was observed when compared with those of Igf1(+/+)
      mice. Immunohistochemical analysis showed that P360 Igf1(-/-) mice suffered
      important structural modifications in the first synapse of the retinal pathway,
      that affected mainly the postsynaptic processes from horizontal and bipolar
      cells. A decrease in bassoon and synaptophysin staining in both rod and cone
      synaptic terminals suggested a reduced photoreceptor output to the inner retina.
      Retinal morphology of the P360 Igf1(+/-) mice showed only small alterations in
      the horizontal and bipolar cell processes, when compared with Igf1(+/+) mice of
      matched age. CONCLUSIONS: In the mouse, IGF-I deficit causes an age-related
      visual loss, besides a congenital deafness. The present results support the use
      of the Igf1(-/-) mouse as a new model for the study of human syndromic deaf
      blindness.

PMID- 22402334
TI  - Sodium-channel blockers might contribute to the prevention of ventricular
      tachycardia in patients with long QT syndrome type 2: a description of 4 cases.
AB  - Four patients with long QT type 2, aged 11 to 18 years from unrelated families,
      with recurrent syncope and polymorhic ventricular tachycardia were studied. Long
      QT syndrome was diagnosed in these children at ages 4 to 7 years. Syncope, QT
      prolongation on electrocardiogram (corrected QT interval >= 490 milliseconds),
      notched T-wave morphology, bradycardia, and polymorphic ventricular arrhythmia
      were found in all of the patients. The KCNH2-L586M; KCNH2-G604S, KCNH2-L1045F;
      and a combined mutation KCNH2 T613M + SCN5A R190G were genotyped. Syncope,
      implantable cardioverter-defibrillator shocks, and tachycardia persisted in these
      patients, although they were receiving a full dose of beta-blocker therapy.
      Adding a sodium-channel blocker (IC class) led to a reduction in the polymorphic
      ventricular arrhythmia. No syncope episodes were registered during the patients'
      8 to 60 months of follow-up on the combined antiarrhythmic therapy. Further
      studies are needed to better define the possible role of sodium-channel blockers
      in patients with long QT type 2.

PMID- 22402335
TI  - Individualized model of torso surface for the inverse problem of
      electrocardiology.
AB  - PURPOSE: We studied the implementation of a patient-specific torso model created
      without the use of magnetic resonance imaging in the inverse problem of
      electrocardiology. METHOD: Three types of inhomogeneous numerical torso models
      were created, with different degrees of adjustment of the outer surface to
      patients, whereas the heart and lung models remained unchanged. The torso models
      were used in the inverse localization of small areas with repolarization changes
      from simulated difference integral QRST maps. The localization error (LE) was
      evaluated as the distance between the centers of the modeled and the inversely
      found area with repolarization changes. RESULTS: The mean LE was 1.88 cm with the
      standard torso model. After adapting the torso shape, the mean LE was 1.83 cm,
      whereas after adapting both, the shape and electrode positions, the mean LE was
      1.02 cm. CONCLUSION: If torso imaging is not available, a torso model with
      adapted shape and electrode positions gives only slightly less accurate results.

PMID- 22402336
TI  - Metal-ceramic bond strength of Co-Cr alloy fabricated by selective laser melting.
AB  - OBJECTIVES: This study was to evaluated the metal-ceramic bond strength of a Co
      Cr dental alloy prepared using a selective laser melting (SLM) technique.
      METHODS: Two groups comprised of twenty Co-Cr metal bars each were prepared using
      either a SLM or traditional lost-wax casting method. Ten bars from each group
      were moulded into standard ISO 9693:1999 dimensions of 25 mm * 3 mm * 0.5 mm with
      1.1 mm of porcelain fused onto an 8 mm * 3 mm rectangular area in the centre of
      each bar. Metal-ceramic bonding was assessed using a three-point bending test.
      Fracture mode analysis and area fraction of adherence porcelain (AFAP) were
      determined by measuring Si content of specimens by SEM/EDS. RESULTS: Student's t
      test within the groups demonstrated no significant difference for the mean bond
      strength between the SLM and traditional cast sample groups. While SEM/EDS
      analysis indicated a mixed fracture mode on the debonding interface of both the
      SLM and the cast groups, the SLM group showed significantly more porcelain
      adherence than the control group (p<0.05). CONCLUSIONS: The SLM metal-ceramic
      system exhibited a bonding strength that exceeds the requirement of ISO
      9691:1999(E) and it even showed a better behaviour in porcelain adherence test
      comparable to traditional cast methods.

PMID- 22402337
TI  - Glossiness perception can be mediated independently of cortical processing of
      colour or texture.

PMID- 22402338
TI  - Disrupted white matter connectivity is associated with reduced cortical thickness
      in the cingulate cortex in schizophrenia.
AB  - INTRODUCTION: Both impaired white matter connectivity and alterations in gray
      matter morphometry have repeatedly been reported in schizophrenia.
      Neurodevelopmental models propose a close linkage between gray matter alterations
      and white matter deficits. However, there are no studies investigating
      alterations in cortical thickness in relation to white matter connectivity
      changes. METHODS: This combined diffusion tensor imaging (DTI) - surface based
      morphometry study examined a potential linkage between disruption in white matter
      connectivity and alterations in cortical thickness. Cortical thickness was
      analyzed using the FreeSurfer software package (version 4.0.5,
      http://surfer.nmr.harvard.edu) in a sample of 19 patients with schizophrenia and
      20 healthy controls. RESULTS: Whole brain node-by-node correlational analysis
      revealed a highly significant association ( r= -.8, p < .0001) between disturbed
      white matter connectivity in the superior temporal cortex and diminished cortical
      thickness in the posterior part of the cingulate cortex (Brodmann area 23/31).
      CONCLUSIONS: This result indicates a significant linkage between disturbed white
      matter connectivity and reduced cortical thickness in a relevant node of the
      default mode network that is held to be of high pathophysiological relevance in
      schizophrenia. The result moreover provides support for the assumption of a
      neurodevelopmental pathogenesis of the disorder.

PMID- 22402339
TI  - Neonatal autoimmune diseases: a critical review.
AB  - Neonatal autoimmune diseases are distinctly rare. Most neonatal autoimmune
      diseases result from the transplacental transfer of maternal antibodies directed
      against fetal or neonatal antigens in various tissues. In neonatal lupus, the
      heart seems to be particularly susceptible. Primary autoimmunity in newborns,
      with the exception of familial autoinflammatory diseases, is virtually non
      existent. The pathophysiologic basis for the development of neonatal autoimmunity
      is not entirely clear, but differences in the neonatal immune system compared
      with the adult immune system, as well as unique characteristics of target
      antigens in the newborn period may be important factors. Neonatal lupus is the
      most common presentation of autoimmunity in the newborn. But the characteristics
      defining neonatal lupus are not well defined and the presentation of neonatal
      lupus differs from that of classical lupus. Other neonatal autoimmune diseases
      involving the interaction between maternal antibodies and fetal/neonatal antigens
      include neonatal anti-phospholipid syndrome, Behcet's disease, neonatal
      autoimmune thyroid disease, neonatal polymyositis and dermatomyositis, neonatal
      scleroderma and neonatal type I diabetes mellitus. While autoantibodies have been
      detected in patients with neonatal autoimmune disease, the pathogenic role of
      autoantibodies has not been well defined. Other mechanisms may play a role in the
      development of neonatal autoimmunity, including fetal/maternal microchimerism and
      aberrant apoptosis of fetal cells. The autoinflammatory syndromes are a
      completely different category, but are also included in discussion of neonatal
      autoimmune diseases. The autoinflammatory syndromes include the cryopyrin
      associated periodic syndromes (CAPS) - familial cold autoinflammatory syndrome
      (FCAS), neonatal onset multisystem inflammatory disease (NOMID) and Muckle-Wells
      syndrome, which all share a common pathophysiologic mechanism.

PMID- 22402340
TI  - The immunobiology of Ro52 (TRIM21) in autoimmunity: a critical review.
AB  - Ro52 is a common target of circulating autoantibodies in autoimmune disease. Data
      indicate that anti-Ro52 antibodies are associated with distinct clinical
      manifestations. It is therefore of major interest to understand how it becomes an
      antigenic target and what cells express this protein under what conditions and
      what cellular function it has. Ro52 contains a RING and a B-box motif, followed
      by a coiled-coil domain and a B30.2 (or PRYSPRY) region in the C-terminal end.
      This molecular structure places Ro52 within the family of tripartite motif
      proteins (TRIM), and it is also denoted TRIM21. Like several other TRIM proteins,
      Ro52 has E3 ligase activity and functions in the process of ubiquitination. Ro52
      is expressed in the immune system as a predominantly cytoplasmic protein that can
      be upregulated and translocate to the nucleus in a proinflammatory environment.
      Reported substrates for Ro52-mediated ubiquitination include IRF3, IRF5, IRF7 and
      IRF8, and via these transcription factors Ro52 regulates type 1 interferon and
      cytokine production. Ro52 is upregulated at the site of autoimmune inflammation,
      such as cutaneous lupus lesions. This implies that Ro52 may have an important
      role in the pathogenesis of autoimmunity, and this paper will review the
      available data on the role of Ro52 in immune responses and autoimmune
      pathogenesis.

PMID- 22402341
TI  - Enhanced biodegradation of hydrocarbon-contaminated sediments using microbial
      fuel cells.
AB  - A sediment microbial fuel cell (MFC) was tested to determine if electron transfer
      from the anaerobic zone of contaminated sediments to the overlying aerobic water
      could facilitate an enhanced and aerobic equivalent degradation of total
      petroleum hydrocarbons (TPH). Results indicate that voltages as high as 190 mV
      (2162 mW/m(3)) were achieved in a sediment MFC with an anode buried in sediments
      containing TPH concentrations at approximately 16,000 mg kg(-1). Additionally,
      after approximately 66 days, the TPH degradation rates were 2% and 24% in the
      open-circuit control sediment MFC and active sediment MFC, respectively.
      Therefore, it appears that applying MFC technology to contaminated sediments
      enhances natural biodegradation by nearly 12 fold. Additionally, a novel sediment
      MFC was designed to provide a cost-effective method of passive oxidation or
      indirect aerobic degradation of contaminants in an otherwise anaerobic
      environment. In addition, the use of a wicking air cathode in this study
      maintained dissolved oxygen concentrations 1-2 mg l(-1) higher than submerged
      cathodes, demonstrating that this technology can be applied to environments with
      either aerobic or anaerobic overlying water and an anaerobic matrix, such as
      shallow lagoon, ponds, and marshes, and groundwater.

PMID- 22402342
TI  - A study of the capacitive deionisation performance under various operational
      conditions.
AB  - Capacitive deionisation (CDI) has many advantages over other desalination
      technologies due to its low energy consumption, less environmental pollution and
      low fouling potential. The objectives of this study are to investigate the effect
      of operational conditions on the CDI electrosorption efficiency and energy
      consumption, to identify ion selectivity in multi-ionic solutions and to probe
      the effect of dissolved reactive silica on the treatment efficiency. A series of
      laboratory scale experiments were conducted using a CDI unit with activated
      carbon electrodes. The electrosorption removal efficiency was inversely related
      to solution temperature, initial total dissolved salts (TDS) concentration and
      the applied flow rate. CDI energy consumption (kWh/m(3)) is directly related to
      the TDS concentration and inversely related to the flow rate. The kinetics
      analysis indicated that the electrosorption followed pseudo-first-order kinetics
      model. Ion selectivity on activated carbon electrodes followed the order of
      Fe(3+)>Ca(2+)>Mg(2+)>Na(+) for cations and SO(4)(2-)>Br(-)>Cl(-)>F(-)>NO(3)(-)
      for anions. It was found that the dissolved silica was not removed by CDI; no
      silica fouling was found. The deterioration of activated carbon electrodes was
      not observed at any time during experiment.

PMID- 22402343
TI  - The effect of hardness on the stability of citrate-stabilized gold nanoparticles
      and their uptake by Daphnia magna.
AB  - The stability and uptake by Daphnia magna of citrate-stabilized gold
      nanoparticles (AuNPs) in three different hardness-adjusted synthetic waters were
      investigated. Negatively charged AuNPs were found to aggregate and settle in
      synthetic waters within 24 h. Sedimentation rates depended on initial particle
      concentrations of 0.02, 0.04, and 0.08 nM AuNPs. Hardness of the synthetic waters
      affected the aggregation of AuNPs and is explained by the compression of diffuse
      double layer of AuNPs due to the increasing ionic strength. The fractal dimension
      of AuNPs in the reaction-limited regime of synthetic waters averaged 2.228+/
      0.126 implying the rigid structures of aggregates driven by the collision of
      small particles with the growing aggregates. Four-day old D. magna accumulated
      more than 90% of AuNPs in 0.04 nM AuNP suspensions without any observed
      mortality. Exposure to pre-aggregated AuNP for 48 h in hard water did not show
      any significant difference in uptake, suggesting D. magna can also ingest settled
      AuNP aggregates. D. magna exposed to AuNPs shed their exoskeleton whereas the
      control did not generate any molts over 48 h. This implies that D. magna removed
      AuNPs on their exoskeleton by producing molts to decrease any adverse effects of
      adhered AuNPs.

PMID- 22402344
TI  - Wild type TDP-43 induces neuro-inflammation and alters APP metabolism in
      lentiviral gene transfer models.
AB  - The transactivation DNA-binding protein (TDP-43) pathology is associated with
      fronto-temporal lobar dementia (FTLD) with ubiquitinated inclusions and some
      cases of Alzheimer's disease (AD). Proteolytic fragments of beta-amyloid
      precursor protein (betaAPP) are detected in AD as well as the cerebrospinal fluid
      (CSF) from FTLD and Amyotrophic Lateral Sclerosis (ALS) patients, suggesting
      alteration in APP processing. Because of the overlap in TDP-43 pathology between
      FTLD and AD, we sought to determine whether there is a relationship between TDP
      43 and APP metabolism. We generated gene transfer models using lentiviral
      delivery of human TDP-43 and Abeta(1-42) into the rat primary motor cortex and
      examined their role 2 weeks post-injection. Expression of TDP-43 and/or Abeta(1
      42) increase pro-inflammatory markers, including Interleukin (IL)-6, tumor
      necrosis factor (TNF-alpha), glial neurofibrillary proteins (GFAP) and ionized
      calcium binding adaptor molecule 1 (IBA-1). Lentiviral Abeta(1-42) up-regulates
      endogenous TDP-43 and promotes its phosphorylation, aggregation and cleavage into
      35 kDa fragments. Inversely, lentiviral TDP-43 expression increases the levels
      and activity of beta-secretase (BACE), accelerating production of APP C-terminal
      fragments (C99) and Abeta(1-40). Here we show that TDP-43 up-regulates APP
      metabolism and suggest a mechanistic link between TDP-43 and BACE.

PMID- 22402345
TI  - Effects of stromal cell-derived factor 1alpha delivered at different phases of
      transient focal ischemia in rats.
AB  - Endogenous stromal cell-derived factor 1alpha (SDF1alpha) has been implicated in
      postischemic tissue repair, suggesting SDF1alpha as a potential therapeutic
      molecule to treat stroke patients. In spite of its potential, no data are
      available regarding the short- and long-term effects of SDF1alpha when it is
      delivered at different phases of stroke. In our study, adenovirus expressing
      SDF1alpha gene (AV-SDF1alpha) was introduced into the boundary of the infarcted
      area either 3 days before or 1 week after ischemia, and behavioral performance
      was measured over 5 weeks. Immediate behavioral and structural amelioration was
      evident when AV-SDF1alpha was injected 3 days before ischemia, which might be the
      result of SDF1alpha-mediated neuroprotection as supported by the TUNEL staining
      and Western blot analysis of active caspase-3. In addition, increase in
      neurogenesis, neuroblast migration, and neural differentiation was also apparent
      in the AV-SDF1alpha-injected brain, which contributed to further amelioration at
      later time points ("delayed response"). On the contrary, when AV-SDF1alpha was
      introduced 1 week post-ischemia (in the subacute phase), significant behavioral
      recovery became apparent beginning 5 weeks after viral delivery. Taken together,
      the therapeutic efficacy of SDF1alpha varied considerably depending on when
      SDF1alpha overexpression was initiated; initiating SDF1alpha overexpression
      before ischemia exerted both immediate and delayed beneficial effects, whereas
      initiating overexpression in the subacute phase exerted only a delayed response.

PMID- 22402346
TI  - The protective effect of sonic hedgehog is mediated by the phosphoinositide
      [corrected] 3-kinase/AKT/Bcl-2 pathway in cultured rat astrocytes under oxidative
      stress.
AB  - In our previous study, we found that the sonic hedgehog (Shh) signaling pathway
      is activated in neurons under oxidative stress and plays a neuro-protective role
      [Dai RL, et al. (2011) Neurochem Res 36:67-75]; we are led to postulate that the
      Shh might be released by astrocytes, thereby protecting neurons against oxidant
      injury. In primary cultured astrocytes of rats, we found that treatment with 100
      MUM H2O2 for 24 h induced a significant increase in the mRNA and protein levels
      of Shh, Patched1, and Gli-1, and the increase was substantially greater in
      astrocytes than in neurons. In the coculture systems of astrocytes and neurons
      under the H2O2 treatment, blocking the Shh signaling pathway with 5E1 (an
      antibody against the N-terminal domain of Shh) could block the neuroprotective
      activity of astrocytes on cocultured neurons. In this study, we found that
      treatment with H2O2 (100-800 MUM) for 24 h caused cell death of astrocytes in a
      concentration-dependent manner. MTT reduction and Trypan Blue exclusion assay
      showed that exogenous Shh increased survival rate of the H2O2-treated astrocytes,
      whereas pretreatment with cyclopamine (a specific inhibitor of the Shh signaling
      pathway) or 5E1 decreased the survival rate of the H2O2-treated astrocytes. Shh
      also inhibited H2O2-induced apoptosis of astrocytes, and this effect could be
      partially reversed by cyclopamine. We also found that Shh promoted the
      phosphorylation of AKT, but had no significant effect on p38 or extracellular
      signal regulated kinases 1 and 2 (ERK 1/2) in H2O2-treated astrocytes. Blocking
      Shh or phosphoinositide 3-kinases (PI3-K)/AKT signaling pathway with cyclopamine
      or LY294002 decreased the survival rate of astrocytes, induced cell apoptosis,
      upregulated the expression of Bax, and downregulated the expression of Bcl-2. We
      are led to conclude that the oxidative stress induces astrocytes to secrete
      endogenous Shh and exogenous administration of Shh might protect the astrocytes
      from oxidative stress by activating PI3-K/AKT/Bcl-2 pathway.

PMID- 22402347
TI  - Kainate induces mobilization of synaptic vesicles at the growth cone through the
      activation of protein kinase A.
AB  - Activation of protein kinase A (PKA) pathway at presynaptic terminals plays a
      crucial role in the supply of synaptic vesicles (SVs) from the reserve pool,
      affecting the steady-state level of activity and the reconstitution of the
      readily releasable pool after intense stimulation. However, the identity of the
      stimuli activating this pathway is undefined. Using fluorescence resonance energy
      transfer and molecular genetic, we show that kainate, through the activation of
      presynaptic kainate receptors, induces PKA activation and enhances synapsin I
      phosphorylation at PKA-specific residues. This leads to a dispersion of synapsin
      I immunoreactivity, which is accompanied by a PKA-dependent increase in the rate
      of SV recycling at the growth cone and by an enhanced miniature excitatory
      postsynaptic currents frequency in mature networks. Selective activation of this
      pathway is induced by the native neurotransmitter glutamate, when applied in the
      high nanomolar range. These data identify glutamate, specifically acting on KARs,
      as one of the stimuli able to induce phosphorylation of synapsin at PKA sites,
      both at the axonal growth cone and at the mature synapse, thus increasing SV
      availability and contributing to plasticity phenomena.

PMID- 22402348
TI  - Early development of spatial patterns of power-law frequency scaling in FMRI
      resting-state and EEG data in the newborn brain.
AB  - Recent studies have revealed spatial and functional relations in the temporal
      dynamics of resting-state functional magnetic resonance imaging (rs-fMRI) or
      electroencephalography (EEG) signals recorded in the adult brain. By modeling the
      frequency power spectrum of resting-state brain signals with a power-law function
      0(f)alpha1/falpha, the power-law exponent alpha has been shown to relate to the
      connectivity patterns of spontaneous brain activity that forms so-called rs-fMRI
      networks in the human adult brain. Here, we present an analysis of the dynamic
      properties of rs-fMRI and EEG signals acquired both in the newborn and adult
      brain, and we demonstrate frequency scaling of a power-law kind for orders of
      magnitude in the hemodynamic (0.01-0.15 Hz) and the electrical (0.2-30 Hz)
      domain. We show that the spatial segregation of resting-state dynamics of
      intrinsic fMRI signals in terms of the power-law exponent alpha is closely
      related to previously delineated resting-state neuronal architecture that
      encompasses primary sensory cortices and associate cortex in newborns. Moreover,
      the spatial profiles of differences in temporal dynamics for rs-fMRI signals
      could also be observed in EEG measurements in the newborn brain, albeit at a
      coarser spatial scale, with larger power-law exponents in occipital and parietal
      cortices compared with signals from the frontal brain.

PMID- 22402349
TI  - Letter from the editor.

PMID- 22402350
TI  - Chemotherapy and immunotherapy combination in advanced prostate cancer.
AB  - In prostate cancer, there is considerable evidence that tumors promote immune
      tolerance starting early in the disease. By suppressing tumors and activating
      immune system homeostatic mechanisms, chemotherapy may help overcome this tumor
      induced immune tolerance. As such, chemotherapy may therefore support improved
      results from novel immune-modulating therapies. Prostate cancer is particularly
      suited for active immunotherapy because prostate tumor cells express a number of
      distinctive surface antigens. Sipuleucel-T, which has recently been approved in
      the United States, is an active immunotherapy that triggers T-cell responses
      against prostate cancer. An exploratory analysis of phase III trial participants
      found a substantial survival benefit to receiving docetaxel some months after
      sipuleucel-T. However, VITAL-2, a phase III trial investigating a prostate cancer
      therapeutic vaccine plus concurrent docetaxel versus standard docetaxel therapy
      in advanced prostate cancer, observed lower overall survival with the vaccine
      regimen. This trial highlights major unresolved questions concerning the optimum
      choice, dosing, and timing of chemotherapy relative to active immunotherapy.
      Patient characteristics, prostate cancer disease stage, and treatment history
      also may influence the response to combined therapy. Advances in biomarker
      validation and trial design are needed to efficiently investigate these issues.

PMID- 22402351
TI  - Differences in the reporting rates of serious allergic adverse events from
      intravenous iron by country and population.
AB  - BACKGROUND: Previous studies have compared rates of adverse events between
      intravenous (IV) iron preparations; however, there has been no comparison of
      adverse event rates by country and population. OBJECTIVES: To compare rates of
      adverse events to IV iron products by country and population. METHODS: All
      adverse events reported from 18 countries from January 1, 2003 to June 30, 2009
      were obtained for iron dextran (ID), iron sucrose (IS), IS similars (ISS), and
      sodium ferric gluconate (FG). Rates of all adverse events and serious adverse
      events (anaphylaxis plus other serious allergic reactions) were calculated as
      number of events per gram of iron sold (gFe) per million inhabitants (mil) * 10
      3. Odds ratios (ORs) were calculated for the risks of adverse events between
      products. RESULTS: Iron use ranged from 1 gFe/mil (Poland) to 48,674 gFe/mil
      (Italy). Rates of all adverse events (reports/gFe/mil * 10-3) varied: for IS, it
      ranged from 0 (Poland, Austria, Czech Republic) to 1,222 (Ireland); for FG, from
      3.3 (Czech Republic) to 183.6 (United States); for ID, from 0.9 (Turkey) to
      46,875 (Switzerland). There were no reports of adverse events in ISS. In a subset
      of countries that used 2 or more iron products and had more than 1 serious
      adverse event, rates (reports/gFe/mil * 10-3) of all adverse events and serious
      adverse events were lowest for IS (39.8 and 1.7), intermediate for FG (54.8 and
      4.5), and greatest for ID (337.7 and 20.5). IS had lower risks for all adverse
      events (OR, 0.63; P<.0001) and serious adverse events (OR, 0.31; P=.001) versus
      FG, and for all adverse events (OR, 0.13; P<.0001) and serious adverse events
      (OR, 0.07; P<.0001) versus ID. FG had lower risks for all adverse events (OR,
      0.20; P<.0001) and serious adverse events (OR, 0.24; P<.0001) versus ID.
      CONCLUSIONS: Considerable international variation existed in the extent and
      choice of iron product and adverse event reporting, suggesting under-reporting in
      some instances. Clinicians should appreciate the differential risks between
      available products, and should critically review local reporting practices.

PMID- 22402352
TI  - Ruxolitinib: the first agent approved for myelofibrosis.

PMID- 22402354
TI  - The generic drug shortage.

PMID- 22402355
TI  - The reemergence of aspirin for the prevention of venous thromboembolism.

PMID- 22402356
TI  - The need for postoperative radiation therapy.

PMID- 22402357
TI  - Metastatic renal cell cancer presenting as a breast mass.

PMID- 22402358
TI  - Late recurrences of renal cell carcinoma at unusual sites: implications for
      patient management.

PMID- 22402359
TI  - Long-term remission of paroxysmal nocturnal hemoglobinuria following
      chemoimmunotherapy for non-Hodgkin lymphoma.

PMID- 22402360
TI  - Chemoimmunotherapy's potential to impact paroxysmal nocturnal hemoglobinuria.

PMID- 22402361
TI  - [Population pharmacokinetics applied to optimising cisplatin doses in cancer
      patients].
AB  - OBJECTIVE: To develop and internally validate a population pharmacokinetics model
      for cisplatin and assess its prediction capacity for personalising doses in
      cancer patients. METHOD: Cisplatin plasma concentrations in forty-six cancer
      patients were used to determine the pharmacokinetic parameters of a two
      compartment pharmacokinetic model implemented in NONMEN VI software.
      Pharmacokinetic parameter identification capacity was assessed using the
      parametric bootstrap method and the model was validated using the nonparametric
      bootstrap method and standardised visual and numerical predictive checks. The
      final model's prediction capacity was evaluated in terms of accuracy and
      precision during the first (a priori) and second (a posteriori) chemotherapy
      cycles. RESULTS: Mean population cisplatin clearance is 1.03 L/h with an
      interpatient variability of 78.0%. Estimated distribution volume at steady state
      was 48.3 L, with inter- and intrapatient variabilities of 31,3% and 11,7%,
      respectively. Internal validation confirmed that the population pharmacokinetics
      model is appropriate to describe changes over time in cisplatin plasma
      concentrations, as well as its variability in the study population. The accuracy
      and precision of a posteriori prediction of cisplatin concentrations improved by
      21% and 54% compared to a priori prediction. CONCLUSION: The population
      pharmacokinetic model developed adequately described the changes in cisplatin
      plasma concentrations in cancer patients and can be used to optimise cisplatin
      dosing regimes accurately and precisely.

PMID- 22402362
TI  - The mechanisms of cerebral vascular dysfunction and neuroinflammation by MMP
      mediated degradation of VEGFR-2 in alcohol ingestion.
AB  - OBJECTIVE: Blood-brain barrier (BBB) dysfunction caused by activation of matrix
      metalloproteinases (MMPs) is a pathological feature in vascular/neurological
      disease. We describe the mechanisms of BBB dysfunction and neuroinflammation as a
      result of MMP-3/9 activation and disruption of vascular endothelial growth factor
      (VEGF)-A/VEGFR-2 interaction, impairing effective angiogenesis. METHODS AND
      RESULTS: We investigate the hypothesis in human brain endothelial cells and
      animal model of chronic alcohol ingestion. Proteome array analysis, zymography,
      immunofluorescence, and Western blotting techniques detected the activation,
      expression, and levels of MMP-3 and MMP-9. We found that degradation of VEGFR-2
      and BBB proteins, for example, occludin, claudin-5, and ZO-1 by MMP-3/9, causes
      rupture of capillary endothelium and BBB leakiness. Impairment of BBB integrity
      was demonstrated by increased permeability of dye tracers and Fluo-3/calcein-AM
      labeled monocyte adhesion or infiltration and decrease in transendothelial
      electric resistance. Alcohol-induced degradation of endothelial VEGFR-2 by MMP
      3/9 led to a subsequent elevation of cellular/serum VEGF-A level. The decrease in
      VEGFR-2 with subsequent increase in VEGF-A level led to apoptosis and
      neuroinflammation via the activation of caspase-1 and IL-1beta release. The use
      of MMPs, VEGFR-2, and caspase-1 inhibitors helped to dissect the underlying
      mechanisms. CONCLUSIONS: Alcohol-induced MMPs activation is a key mechanism for
      dysfunction of BBB via degradation of VEGFR-2 protein and activation of caspase-1
      or IL-1beta release. Targeting VEGF-induced MMP-3/9 activation can be a novel
      preventive approach to vascular inflammatory disease in alcohol abuse.

PMID- 22402363
TI  - Metalloproteinase processing of HBEGF is a proximal event in the response of
      human aortic endothelial cells to oxidized phospholipids.
AB  - OBJECTIVE: Atherosclerosis is a chronic inflammatory disease initiated by
      monocyte recruitment and retention in the vessel wall. An important mediator of
      monocyte endothelial interaction is the chemokine interleukin (IL)-8. The
      oxidation products of phospholipids, including oxidized 1-palmitoyl-2-arachidonyl
      sn-glycerol-3-phosphocholine (Ox-PAPC), accumulate in atherosclerotic lesions and
      strongly induce IL-8 in human aortic endothelial cells (HAECs). The goal of this
      study was to identify the proximal events leading to induction of IL-8 by Ox-PAPC
      in vascular endothelial cells. METHODS AND RESULTS: In a systems genetics
      analysis of HAECs isolated from 96 different human donors, we showed that heparin
      binding EGF-like growth factor (HBEGF) transcript levels are strongly correlated
      to IL-8 induction by Ox-PAPC. The silencing and overexpression of HBEGF in HAECs
      confirmed the role of HBEGF in regulating IL-8 expression. HBEGF has been shown
      to be stored in an inactive form and activation is dependent on processing by a
      dysintegrin and metalloproteinases (ADAM) to a form that can activate the
      epidermal growth factor (EGF) receptor. Ox-PAPC was shown to rapidly induce HBEGF
      processing and EGF receptor activation in HAECs. Using siRNA we identified 3
      ADAMs that regulate IL-8 induction and directly demonstrated that Ox-PAPC
      increases ADAM activity in the cells using a substrate cleavage assay. We provide
      evidence for one mechanism of Ox-PAPC activation of ADAM involving covalent
      binding of Ox-PAPC to cysteine on ADAM. Free thiol cysteine analogs showed
      inhibition of IL-8 induction by Ox-PAPC, and both a cysteine analog and a cell
      surface thiol blocker strongly inhibited ADAM activity induction by Ox-PAPC.
      Using microarray analyses, we determined that this ADAM pathway may regulate at
      least 30% of genes induced by Ox-PAPC in HAECs. CONCLUSIONS: This study is the
      first report demonstrating a role for the ADAM-HBEGF-EGF receptor axis in Ox-PAPC
      induction of IL-8 in HAECs. These studies highlight a role for specific ADAMs as
      initiators of Ox-PAPC action and provide evidence for a role of covalent
      interaction of Ox-PAPC in activation of ADAMs.

PMID- 22402364
TI  - c-Myc is required for proper coronary vascular formation via cell- and gene
      specific signaling.
AB  - OBJECTIVE: Although significant research has detailed angiogenesis during
      development and cancer, little is known about cardiac angiogenesis, yet it is
      critical for survival following pathological insult. The transcription factor c
      Myc is a target of anticancer therapies because of its mitogenic and
      proangiogenic induction. In the current study, we investigate its role in cardiac
      angiogenesis in a cell-dependent and gene-specific context. METHODS AND RESULTS:
      Angiogenesis assays using c-Myc-deficient cardiac endothelial cells and
      fibroblasts demonstrate that c-Myc is essential to vessel formation, and
      fibroblast-mediated vessel formation is dependent on c-Myc expression in
      fibroblasts. Gene analyses revealed that c-Myc-mediated gene expression is unique
      in cardiac angiogenesis and varies in a cell-dependent manner. In vitro 3
      dimensional cultures demonstrated c-Myc's role in the expression of secreted
      angiogenic factors, while also providing evidence for c-Myc-mediated cell-cell
      interactions. Additional in vivo vascular analyses support c-Myc's critical role
      in capillary formation and vessel patterning during development and also in
      response to a pathological stimulus where its expression in myocytes is required
      for angiogenic remodeling. CONCLUSIONS: These data demonstrate that proper c-Myc
      expression in cardiac fibroblasts and myocytes is essential to cardiac
      angiogenesis. These results have the potential for novel therapeutic applications
      involving the angiogenic response during cardiac remodeling.

PMID- 22402365
TI  - MicroRNAs in the growth plate are responsive to nutritional cues: association
      between miR-140 and SIRT1.
AB  - MicroRNAs (miRNAs) have been reported to be involved in a variety of functions,
      including skeletal development and longitudinal growth. The aim of this study was
      to investigate the role of miRNAs in food-restriction-induced growth attenuation
      and nutrition-induced catch-up growth in the epiphyseal growth plate (EGP).
      Prepubertal rats were fed ad libitum or were subjected to 40% food restriction
      for 10 days followed by a renewal of the regular food supply. At sacrifice,
      tibial EGPs were excised, and the total RNA was extracted and loaded on miRNA
      microarrays. The miRNA microarray yielded more than 400 miRNAs that are expressed
      in the EGP of mature animals. Results were confirmed by quantitative polymerase
      chain reaction. Chondrocyte-specific miR-140-3p showed the highest expression in
      the mature EGP, and it was one of the few miRNAs that were significantly reduced
      following nutrition restriction. Changes in predicted miRNA targets were then
      followed with Western immunoblotting. Direct binding was demonstrated using
      exogenous miRNA, the 3'UTR of the target mRNA and a luciferase reporter assay.
      Nutrition restriction induced an increase in the level of the miR-140-3p target,
      NAD+-dependent SIRT1. This study is the first to show that SIRT1 and miRNAs
      expressed in the mature EGP are responsive to nutritional cues. Nutrition-induced
      epigenetic regulation of growth activates two parts of the epigenetic world -
      miRNAs and histone deacetylases - that are interconnected. Deciphering the role
      of epigenetic regulation in growth may open a new era of research and pave the
      way for the development of new treatments for children with growth disorders.

PMID- 22402366
TI  - Investigation of the molecular response to folate metabolism inhibition.
AB  - We investigated the molecular response to folate metabolism inhibition by
      exposing human lymphoblast cell lines to the methionine adenosyltransferase
      inhibitor cycloleucine. We carried out microarray analysis on replicate control
      and exposed cells by examining 47,000 transcripts on the Affymetrix HG U133 plus
      2.0 arrays. We identified 13 genes that we considered reliable responders to
      cycloleucine treatment: chemokine receptor 3 (CXCR3), prostaglandin-endoperoxide
      synthase 2, growth arrest-specific 7, reduced folate carrier, klotho beta, early
      growth response 1, diaphanous homolog 3, prostaglandin D2 synthase (PGDS),
      butyrophilin-like 9, low-density lipoprotein receptor-related protein 11,
      chromosome 21 orf15, G-protein-coupled receptor 98 (GPR98) and cystathionine-beta
      synthase (CBS). We further demonstrated that four of these genes, CXCR3, PGDS,
      GPR98 and CBS, consistently responded to cycloleucine treatment in additional
      experiments over a range of concentrations. We carried out gene-specific DNA
      methylation analysis on five genes, including CBS, and found no evidence that DNA
      methylation changes were mediating the gene expression changes observed. Pathway
      analysis of the microarray data identified four pathways of relevance for
      response to cycloleucine; the immune response NF-AT signaling pathway was the
      most statistically significant. Comparison with other gene expression studies
      focusing on folate deficiency revealed that gene products related to immune cells
      or the immune response is a common theme. This indicates that apart from their
      role in the immune response, it is likely that these gene products may also have
      a role to play in the cellular response to folate status.

PMID- 22402367
TI  - Curcumin reduces the cardiac ischemia-reperfusion injury: involvement of the toll
      like receptor 2 in cardiomyocytes.
AB  - Curcumin, a polyphenolic compound derived from turmeric, has protective effects
      on myocardial injury through attenuation of oxidative stress and inflammation.
      Toll-like receptor 2 (TLR2), a key mediator of the innate immune system, is
      involved in myocardial infarction and examined if controlled by curcumin. Rat
      cardiomyocytes (CMs) were stimulated with tumor necrosis factor (TNF)-alpha,
      peptidoglycan (PGN) or hypoxia/reoxygenation (H/R) with or without curcumin
      pretreatment. Sprague-Dawley rats were fed curcumin (300 mg/kg/day) 1 week before
      cardiac ischemia/reperfusion (I/R) injury. The expression level of TLR2 and
      cardiac function were assessed. Both mRNA and protein of TLR2 were up-regulated
      in infarcted myocardium, while TLR4 remained unchanged. In CMs, TLR2 and monocyte
      chemoattractant protein (MCP)-1 mRNAs were increased by TNF-alpha, PGN or H/R,
      whereas they were blunted by curcumin. Immunofluorescence staining of CMs also
      showed that TLR2 and MCP-1 were increased after H/R, whereas curcumin-pretreated
      CMs were not. In animal study, 2 weeks after I/R, TLR2 was increased in the
      infarct zone, whereas it stayed unchanged in the Cur+I/R group. Macrophage
      infiltration (CD68), high-mobility group box 1 and fibrosis were increased in the
      I/R group, whereas they were decreased in the Cur+I/R group. Connexin 43 was
      reduced in the I/R group, while it recovered significantly in the Cur+I/R group.
      Cardiac contractility in the Cur+I/R group was also improved compared with that
      in the I/R group (max dp/dt in Cur+I/R group: 9660+/-612 vs. I/R group: 8119+/
      366, P<.05). These results suggest that selective inhibition of TLR2 by curcumin
      could be preventive and therapeutic for myocardial infarction.

PMID- 22402368
TI  - Differential regulation of CD4(+) T helper cell responses by curcumin in
      experimental autoimmune encephalomyelitis.
AB  - Nutraceuticals and phytochemicals are important regulators of human health and
      diseases. Curcumin is a polyphenolic phytochemical isolated from the rhizome of
      the plant Curcuma longa (turmeric) that has been traditionally used for the
      treatment of inflammation and wound healing for centuries. Systematic analyses
      have shown that curcumin exerts its beneficial effects through antioxidant,
      antiproliferative and anti-inflammatory properties. We and others have shown
      earlier that curcumin ameliorates experimental autoimmune encephalomyelitis (EAE)
      model for multiple sclerosis. In this study, we show that C57BL/6 mice induced to
      develop EAE express elevated levels of interferon (IFN) gamma and interleukin
      (IL)-17 in the central nervous system (CNS) and lymphoid organs that decreased
      significantly following in vivo treatment with curcumin. The EAE mice also showed
      elevated expression of IL-12 and IL-23 that decreased after treatment with
      curcumin. Ex vivo and in vitro treatment with curcumin resulted in a dose
      dependent decrease in the secretion of IFNgamma, IL-17, IL-12 and IL-23 in
      culture. The inhibition of EAE by curcumin was also associated with an up
      regulation of IL-10, peroxisome proliferator activated receptor gamma and
      CD4(+)CD25(+-)Foxp3(+) Treg cells in the CNS and lymphoid organs. These findings
      highlight that curcumin differentially regulates CD4(+) T helper cell responses
      in EAE.

PMID- 22402369
TI  - Disturbed zinc homeostasis in diabetic patients by in vitro and in vivo analysis
      of insulinomimetic activity of zinc.
AB  - Disturbances of zinc homeostasis have been observed in several diseases,
      including diabetes mellitus. To further characterize the association between zinc
      and diabetes, we recruited 75 patients with type 1 or type 2 diabetes and 75
      nondiabetic sex-/age-matched control subjects in order to analyze differences
      concerning human zinc transporter 8 (hZnT-8) expression, single nucleotide
      polymorphisms (SNPs) in the genes of hZnT-8 as well as metallothionein 1A and
      serum/intracellular zinc. Furthermore, we investigated the relation between
      insulin and zinc homeostasis in type 2 diabetic subjects and consolidated our
      results by in vitro analysis of the effect of insulin on cellular zinc status and
      by analysis of the modulation of insulin signal transduction by intracellular
      zinc homeostasis. Concerning the expression of hZnT-8 and the SNPs analyzed, we
      did not observe any differences between diabetic and control subjects. Serum zinc
      was significantly lower in diabetic patients compared to controls, and
      intracellular zinc showed the same tendency. Interestingly, type 2 diabetes
      patients treated with insulin displayed lower serum zinc compared to those not
      injecting insulin. In vitro analyses showed that insulin leads to an increase in
      intracellular zinc and that insulin signaling was enhanced by elevated
      intracellular zinc concentrations. In conclusion, we show that type 1 and type 2
      diabetic patients suffer from zinc deficiency, and our results indicate that zinc
      supplementation may qualify as a potential treatment adjunct in type 2 diabetes
      by promoting insulin signaling, especially in zinc-deficient subjects.

PMID- 22402370
TI  - Infant formula supplemented with polyamines alters the intestinal microbiota in
      neonatal BALB/cOlaHsd mice.
AB  - Polyamines play a critical role in the development of intestinal and immune
      systems during the infant breastfeeding period, but the effect of polyamines on
      the microbiota has not been reported. The aim of our study was to characterize
      the impact on the colonization pattern in neonatal BALB/cOlaHsd mice after
      supplementing an infant formula (IF) with a mixture of putrescine (PUT),
      spermidine (SPD) and spermine (SPM). A total of 48 pups (14 days old) were
      randomly assigned to 4-day intervention groups as follows: breast-fed (unweaned)
      pups (n=12); weaned pups (n=12) fed an infant formula (IF); weaned pups (n=12)
      fed an IF enriched with a low concentration of PUT, SPD and SPM (2.10, 22.05 and
      38.00 MUg/day, respectively); and weaned pups (n=12) fed with IF enriched with a
      high concentration of PUT, SPD and SPM (8.40, 88.20 and 152.00 MUg/day,
      respectively) of polyamines in accordance with normal proportions found in human
      milk. Microbiota composition was analyzed by fluorescent in situ hybridization
      (FISH) with flow cytometry detection. Microbiota changes in formula-fed mice were
      significantly greater following supplementation with polyamines (P<.01).
      Bifidobacterium group bacteria, Akkermansia-like bacteria and Lactobacillus
      Enterococcus group levels were higher in the groups fed infant formula
      supplemented with polyamines, resulting in even higher numbers of bacteria than
      in the breastfed pups. Our findings indicate that infant formulas enriched with
      polyamines may interact with gut microbiota, suggesting that further studies in
      human infants are required to assess the impact of polyamines on both growth and
      microbiota levels.

PMID- 22402371
TI  - Cross-cultural adaptation and measurement properties of an Italian version of the
      Western Ontario Shoulder Instability Index (WOSI).
AB  - STUDY DESIGN: Clinical measurement study. OBJECTIVES: To translate and cross
      culturally adapt the Western Ontario Shoulder Instability Index (WOSI) into
      Italian, and to evaluate its measurement properties in patients with shoulder
      instability secondary to a first-time traumatic anterior dislocation. BACKGROUND:
      The WOSI was developed for English-speaking patients. To date, no Italian version
      of the WOSI exists. METHODS: The WOSI was cross-culturally adapted to Italian
      according to established guidelines. Sixty-four (16 women, 48 men) patients with
      unilateral shoulder anterior instability were prospectively recruited for the
      purposes of this study. Internal consistency, test-retest reliability, construct
      validity, and responsiveness of the WOSI were evaluated. RESULTS: The Italian
      version of the WOSI showed a high degree of internal consistency, with a Cronbach
      alpha of .93 (95% confidence interval [CI]: 0.91, 0.96). The test-retest
      reliability was high for both short-term (3 days, 64 patients) and medium-term
      (14 weeks, 20 patients) test-retest, with intraclass correlation coefficients of
      0.95 (95% CI: 0.90, 0.97) and 0.92 (95% CI: 0.89, 0.95), respectively. The WOSI
      was more closely correlated to the Disabilities of the Arm, Shoulder and Hand
      questionnaire than to the Medical Outcomes Study 36-Item Short-Form Health Survey
      (r = 0.794 and 0.113, respectively). The receiver-operating-characteristic curve
      analysis revealed that the WOSI was more responsive than the Disabilities of the
      Arm, Shoulder and Hand questionnaire (P = .03), with an area under the curve of
      0.90 (95% CI: 0.78, 0.97) for the WOSI and 0.76 (95% CI: 0.61, 0.88) for the
      Disabilities of the Arm, Shoulder and Hand questionnaire. CONCLUSION: The Italian
      version of the WOSI is a valid, reliable, and responsive tool that can be used to
      measure function in Italian-speaking patients with shoulder instability due to a
      first-time traumatic anterior dislocation.

PMID- 22402372
TI  - Fever in a kidney transplant recipient: no facts and many interactions.

PMID- 22402373
TI  - [Ventricular arrhythmias in continuous bigeminism: an atypical form of idiopathic
      arrhythmias].

PMID- 22402374
TI  - [Acremonium spp. pneumonia in a patient with acute myelogenous leukemia].

PMID- 22402375
TI  - [Thromboembolic disease: the challenge is in the prophylaxis].

PMID- 22402376
TI  - Sensitivity analysis of an asymmetric Monte Carlo beam model of a Siemens Primus
      accelerator.
AB  - The assumption of cylindrical symmetry in radiotherapy accelerator models can
      pose a challenge for precise Monte Carlo modeling. This assumption makes it
      difficult to account for measured asymmetries in clinical dose distributions. We
      have performed a sensitivity study examining the effect of varying symmetric and
      asymmetric beam and geometric parameters of a Monte Carlo model for a Siemens
      PRIMUS accelerator. The accelerator and dose output were simulated using modified
      versions of BEAMnrc and DOSXYZnrc that allow lateral offsets of accelerator
      components and lateral and angular offsets for the incident electron beam. Dose
      distributions were studied for 40 * 40 cm2 fields. The resulting dose
      distributions were analyzed for changes in flatness, symmetry, and off-axis ratio
      (OAR). The electron beam parameters having the greatest effect on the resulting
      dose distributions were found to be electron energy and angle of incidence, as
      high as 5% for a 0.25 degrees  deflection. Electron spot size and lateral offset
      of the electron beam were found to have a smaller impact. Variations in photon
      target thickness were found to have a small effect. Small lateral offsets of the
      flattening filter caused significant variation to the OAR. In general, the
      greatest sensitivity to accelerator parameters could be observed for higher
      energies and off-axis ratios closer to the central axis. Lateral and angular
      offsets of beam and accelerator components have strong effects on dose
      distributions, and should be included in any high-accuracy beam model.

PMID- 22402377
TI  - Low-energy broad-beam photon shielding data for constituents of concrete.
AB  - The ability of concrete to attenuate ionizing radiation intensity is assessed
      using its linear or mass attenuation coefficient. In this work, the broad-beam
      linear and mass attenuation coefficients of different types of soils and cements
      used for making concrete were measured at different photon energies (60-1333
      keV), nearly spanning the diagnostic photon energy range, using a NaI detector.
      The mass attenuation coefficients of cement decreased from 0.133 +/- 0.002 at 60
      keV to 0.047 +/- 0.003 at 1332.5 keV. For soils, the mass attenuation coefficient
      of those collected from the beach was the highest, decreasing from 0.176 +/-
      0.003 cm2/g at 60 keV to 0.054 +/- 0.001 cm2/g at 1332.5 keV. Land soils had the
      least value, decreasing from 0.124 +/- 0.002 cm2/g at 60 keV to 0.044 +/- 0.003
      cm2/g at 1332.5 keV. Limestone had smaller mass attenuation coefficients than the
      cement produced using it. The implication of the above is that for making
      concrete, beach sand should be preferred as the sand component of the concrete.
      Models of the form MU(L) = A(E) exp[B(E)rho] and MU(m) = alphaln(E)+beta are
      proposed for fitting the linear attenuation coefficient and mass attenuation
      coefficient data, respectively.

PMID- 22402378
TI  - Feasibility of a remote, automated daily delivery verification of volumetric
      modulated arc therapy treatments using a commercial record and verify system.
AB  - Volumetric-modulated arc therapy (VMAT) is an effective but complex technique for
      delivering radiation therapy. VMAT relies on precise combinations of dose rate,
      gantry speed, and multileaf collimator (MLC) shapes to deliver intensity
      modulated patterns. Such complexity warrants the development of correspondingly
      robust performance verification systems. In this work, we report on a remote,
      automated software system for daily delivery verification of VMAT treatments. The
      performance verification software system consists of three main components: (1) a
      query module for retrieving daily MLC, gantry, and jaw positions reported by the
      linear accelerator control system to the record and verify system; (2) an
      analysis module which reads the daily delivery report generated from the database
      query module, compares the reported treatment positions against the planned
      positions, and compiles delivery position error reports; and (3) a graphical
      reporting module which displays reports initiated by a user anywhere within the
      institutional network or which can be configured to alert authorized users when
      predefined tolerance values are exceeded. The utility of the system was
      investigated through analysis of patient data collected at our clinic. Nearly
      2500 VMAT fractions have been analyzed with the delivery verification system at
      our institution. The average percentage of reported MLC leaf positions within 3
      mm, gantry positions within 2 degrees , and jaw positions within 3 mm of their
      planned positions was 92.9% +/- 5.5%, 95.9%+/- 2.9%, and 99.7% +/- 0.6%,
      respectively. The level of agreement between planned and reported MLC positions
      decreased for treatment plans requiring larger MLC leaf movements between control
      points. Differences in the reported MLC position error between the delivery
      verification system and data extracted manually from the control system were
      noted; however, the differences are likely systematic and, therefore, may be
      characterized if appropriately accounted for. Further investigation is needed to
      confirm the utility and accuracy of the system.

PMID- 22402379
TI  - Modified dose difference method for comparing dose distributions.
AB  - The quantitative comparison of two-dimensional dose distributions (e.g.,
      calculated versus measured) has become a key issue in intensity-modulated
      radiotherapy (IMRT) QA. We proposed a new evaluation method referred to as
      modified dose difference (MDdiff) evaluation. Hereinafter, features and
      effectiveness of the MDdiff evaluation method will be described. In this work,
      the formalism of MDdiff was defined by introducing a dimensionless parameter
      beta(r)(DG)(r(-->)(r)). A new formalism is compared to a gamma method, and the
      MDdiff and the gamma method are respectively applied to patient-specific IMRT QA.
      The calculation of the evaluation of dose distributions was performed using a C++
      program. Evaluations were performed by counting the number of data points
      satisfying MDdiff >= (1/2)deltaD0, gamma >= 1. The evaluation result of dose
      distributions using the MDdiff method had the same tendency as the evaluation
      result using the gamma evaluation method. The modified dose difference tool also
      provides a quantitative method for comparing two dose distributions like the
      gamma evaluation. Furthermore, many problems of gamma evaluation are resolved.

PMID- 22402380
TI  - A line-profile based double partial fusion method for acquiring planning CT of
      oversized patients in radiation treatment.
AB  - True 3D CT dataset for treatment planning of an oversized patient is difficult to
      acquire due to the bore size and field of view (FOV) reconstruction. This project
      aims to provide a simple approach to reconstruct true CT data for oversize
      patients using CT scanner with limited FOV by acquiring double partial CT (left
      and right side) images. An efficient line profile-based method has been developed
      to minimize the difference of the CT numbers in the overlapping region between
      the right and left images and to generate a complete true 3D CT dataset in the
      natural state. New image processing modules have been developed and integrated to
      the Insight Segmentation & Registration Toolkit (ITK 3.6) package. For example,
      different modules for image cropping, line profile generation, line profile
      matching, and optimized partial image fusion have been developed. The algorithm
      has been implemented for images containing the bony structure of the spine and
      tested on 3D CT planning datasets from both phantom and real patients with
      satisfactory results in both cases. The proposed optimized line profile-based
      partial registration method provides a simple and accurate method for acquiring a
      complete true 3D CT dataset for an oversized patient using CT scanning with small
      bore size, that can be used for accurate treatment planning.

PMID- 22402381
TI  - A semi-empirical model for the therapeutic range shift estimation caused by
      inhomogeneities in proton beam therapy.
AB  - The purpose of this study was to devise a simple semi-empirical model to estimate
      the range shift in clinical practices with high-Z inhomogeneity in proton beam. A
      semi-empirical model utilizing the logarithmic dependence on Z in stopping power
      from Bohr's classical approach has been developed to calculate the range shift
      due to the presence of inhomogeneity. Range shift from metallic plates of atomic
      number Z of various thicknesses were measured in water using a parallel plate
      ionization chamber and calculated with the FLUKA Monte Carlo code. The proton
      range shifts for bone and polymethyl methacrylate (PMMA) were estimated using the
      semi-empirical model and compared with Monte Carlo calculation. The semi
      empirical equation to determine range shift and water equivalent thickness is
      presented. The model predicts a shift of the therapeutic range to within 2.5%
      accuracy for initial proton energies of 50 to 250 MeV and atomic numbers from 3.3
      (effective Z for water) to 82. This equation is independent of beam energy, and
      thus provides range shift from high-Z materials without the knowledge of proton
      energy. The proposed method of calculating the therapeutic range shift accurately
      requires only knowledge of the effective or actual atomic number of the
      inhomogeneity and the thickness of the inhomogeneity along the beam direction.
      The model generalizes the range shift calculation for any material based on its
      effective atomic number, and permits reliable prediction of the range shift for
      material combinations where no data is currently available. The proposed model
      can be readily implemented in routine clinical practice for proton range shift
      estimation and quality assurance on the treatment planning.

PMID- 22402383
TI  - Impact of the Tiloop Bra(r) mesh in CT images and dose delivery in breast
      radiotherapy.
AB  - A new titanized breast mesh, TiLOOP Bra, is currently available for implantation
      in patients who require radiotherapy. The purpose of this work is to study the
      dosimetric effect of the presence of a TiLOOP Bra mesh on breast radiation
      treatment and radiographic imaging. The dosimetric effects have been measured for
      three X-ray energies: 1.25 MeV, 6 MV and 18 MV, using radiochromic films placed
      at three different depths. These depths are representative of mesh location in
      breast during the radiotherapy treatment and hence, are of interest in this
      study. In order to assess the disturbance in a radiographic image, different
      computed tomographic (CT) studies of the mesh have been performed. The absorbed
      dose differences with and without the mesh are less than 1%. No metallic
      artifacts have been observed in radiographic images associated with the mesh, nor
      significant disturbances in Hounsfield Units. The TiLOOP Bra mesh does not
      disturb the dosimetry of a typical radiotherapy treatment and its influence in
      the quality of the CT scan required for planning is negligible.

PMID- 22402382
TI  - The extent and serial pattern of interfractional variation in patients with whole
      pelvic irradiation: a study using a kilovoltage orthogonal on-board imager.
AB  - The purpose of this study is to assess the extent and serial pattern of setup
      error of conventional fractionated whole pelvic irradiation using a kilovoltage
      on-board imager. The daily on-board images of 69 patients were matched with the
      digitally reconstructed radiographs of simulation on the basis of pelvic bony
      structure. The shifts along x- (lateral), y- (longitudinal), and z- (vertical)
      axes, and the 3D vector, were measured. The shift between an origin of the first
      fraction and each fraction (Deltashift(1st)) and the shift between an isocenter
      of simulation and each fraction (Deltashift(Sim)) were calculated. To evaluate
      serial changes, the shifts of each fraction were classified into four consecutive
      sessions, and an ANOVA and chi-square test were used. The systematic error of the
      Deltashift(Sim) and Deltashift(1st) were 2.72 and 1.43 mm along the x-axis, 2.98
      and 1.28 mm along the y-axis, and 4.26 and 2.39 mm along the z-axis,
      respectively. The Deltashift(Sim) and Deltashift(1st) >= 5 mm of the 3D vector
      occurred in 54.3% and 23.1%, respectively. The recommended margins to cover setup
      error in case of using Deltashift(1st) were 3.81, 3.54, and 6.01 mm along x-, y-,
      and z-axes, whereas those using Deltashift(Sim) were 6.39, 6.95, and 9.95 mm,
      respectively. With the passage of time, the Deltashift(1st) >= 5 mm of 3D vector
      and along any axis in supine setup increased from 14.1% for first session to
      22.5% for fourth session (p=0.027) and from 10.8% to 18.5% (p = 0.034),
      respectively. In prone setup, first session was better than others in the
      Deltashift(1st) >= 5 mm of 3D vector and along any axis. It is expected that the
      correction using the on-board images on the first fraction improves geometrical
      uncertainties and reduces the margin for target coverage. Daily continuous OBI
      follow-up during conventional fractionated pelvic irradiation can increase the
      reproducibility and be more effective in the late period.

PMID- 22402384
TI  - Independent evaluation of an in-house brachytherapy treatment planning system
      using simulation, measurement and calculation methods.
AB  - Accuracy of treatment planning systems may significantly influence the efficacy
      of brachytherapy. The purpose of this work is a detailed, varied and independent
      evaluation of an in-house brachytherapy treatment planning software called STPS.
      Operational accuracy of STPS was investigated. Geometric tests were performed to
      validate entry and reconstruction of positional information from scanned
      orthogonal films. MCNP4C Monte Carlo code and TLDs were used for simulation and
      experimental measurement, respectively. STPS data were also compared with those
      from a commercial planning system (Nucletron PLATO). Discrepancy values between
      MCNP and STPS data and also those of PLATO and STPS at Manchester system dose
      prescription points (AL and AR) of tandem and ovoid configurations were 2.5% +/-
      0.5% and 5.4% +/- 0.4%, respectively. Similar results were achieved for other
      investigated configurations. Observed discrepancies between MCNP and STPS at the
      dose prescription point and at 1 cm from the tip of the vaginal applicator were
      4.5% and 25.6% respectively, while the discrepancy between the STPS and PLATO
      data at those points was 2.3%. The software showed submillimeter accuracy in its
      geometrical reconstructions. In terms of calculation accuracy, similar to PLATO,
      as attenuation of the sources and applicator body is not considered, dose was
      overestimated at the tip of the applicator, but based on the available criteria,
      dose accuracy at most points were acceptable. Our results confirm STPS's
      geometrical and operational reliability, and show that its dose computation
      accuracy is comparable to an established commercial TPS using the same algorithm.

PMID- 22402385
TI  - In vivo proton dosimetry using a MOSFET detector in an anthropomorphic phantom
      with tissue inhomogeneity.
AB  - When in vivo proton dosimetry is performed with a metal-oxide semiconductor field
      effect transistor (MOSFET) detector, the response of the detector depends
      strongly on the linear energy transfer. The present study reports a practical
      method to correct the MOSFET response for linear energy transfer dependence by
      using a simplified Monte Carlo dose calculation method (SMC). A depth-output
      curve for a mono-energetic proton beam in polyethylene was measured with the
      MOSFET detector. This curve was used to calculate MOSFET output distributions
      with the SMC (SMC(MOSFET)). The SMC(MOSFET) output value at an arbitrary point
      was compared with the value obtained by the conventional SMC(PPIC), which
      calculates proton dose distributions by using the depth-dose curve determined by
      a parallel-plate ionization chamber (PPIC). The ratio of the two values was used
      to calculate the correction factor of the MOSFET response at an arbitrary point.
      The dose obtained by the MOSFET detector was determined from the product of the
      correction factor and the MOSFET raw dose. When in vivo proton dosimetry was
      performed with the MOSFET detector in an anthropomorphic phantom, the corrected
      MOSFET doses agreed with the SMC(PPIC) results within the measurement error. To
      our knowledge, this is the first report of successful in vivo proton dosimetry
      with a MOSFET detector.

PMID- 22402386
TI  - Dosimetric effects of jaw tracking in step-and-shoot intensity-modulated
      radiation therapy.
AB  - The purpose of this work was to determine the dosimetric benefit to normal
      tissues by tracking the multi-leaf collimator (MLC) apertures with the photon
      jaws in step-and-shoot intensity-modulated radiation therapy (IMRT) on the Varian
      2100 platform. Radiation treatment plans for ten thoracic, three pediatric, and
      three head and neck cancer patients were converted to plans with the jaws
      tracking each segment's MLC apertures, and compared to the original plans in a
      commercial radiation treatment planning system (TPS). The change in normal tissue
      dose was evaluated in the new plan by using the parameters V5, V10, and V20
      (volumes receiving 5, 10 and 20 Gy, respectively) in the cumulative dose-volume
      histogram for the following structures: total lung minus gross target volume,
      heart, esophagus, spinal cord, liver, parotids, and brainstem. To validate the
      accuracy of our beam model, MLC transmission was measured and compared to that
      predicted by the TPS. The greatest changes between the original and new plans
      occurred at lower dose levels. In all patients, the reduction in V20 was never
      more than 6.3% and was typically less than 1%; the maximum reduction in V5 was
      16.7% and was typically less than 3%. The variation in normal tissue dose
      reduction was not predictable, and we found no clear parameters that indicated
      which patients would benefit most from jaw tracking. Our TPS model of MLC
      transmission agreed with measurements with absolute transmission differences of
      less than 0.1% and, thus, uncertainties in the model did not contribute
      significantly to the uncertainty in the dose determination. We conclude that the
      amount of dose reduction achieved by collimating the jaws around each MLC
      aperture in step-and-shoot IMRT is probably not clinically significant.

PMID- 22402388
TI  - Analysis of the optimum internal margin for respiratory-gated radiotherapy using
      end-expiratory phase assessments using a motion phantom.
AB  - We aimed to optimize internal margin (IM) determination for respiratory-gated
      radiotherapy using end-expiratory phase assessments using a motion phantom. Four
      dimensional computed tomography (4D CT) data were acquired using a GE LightSpeed
      RT CT scanner, a respiratory-gating system, and a motion phantom designed to move
      sinusoidally. To analyze the accuracy of 4D CT temporal resolution, a 25.4 mm
      diameter sphere was inserted into the motion phantom, and we measured the
      differences in sphere diameters between static and end-exhalation phase images.
      In addition, the IM obtained from the maximum intensity projection within the
      gating window (MIP(GW)) image was compared to theoretical value. Cranial-caudal
      motion displacement ranged from 5.0 to 30.0 mm, and the respiratory period ranged
      from 2.0 to 6.0 sec. Differences in sphere diameters between static and end
      exhalation phase images ranged from 0.37 to 4.6 mm, with 5.0-mm and 30 mm target
      displacements, respectively. Differences between the IM obtained from the MIP(GW)
      and the theoretical values ranged from 1.12 to 6.23 mm with 5.0mm and 30 mm
      target displacements, respectively. These differences increased in proportion to
      the target velocity due to a motion artifact generated during tube rotation. In
      this study, the IMs obtained using the MIPGW image were overestimated in all
      cases. We therefore propose that the internal target volume (ITV) for respiratory
      gated radiotherapy should be determined by adding the calculated value to the end
      exhalation phase image. We also demonstrate a methodology for subtracting motion
      artifacts from the ITV using a motion phantom.

PMID- 22402387
TI  - Target repositional accuracy and PTV margin verification using three-dimensional
      cone-beam computed tomography (CBCT) in stereotactic body radiotherapy (SBRT) of
      lung cancers.
AB  - The purpose of this study was to assess target repositional accuracy with respect
      to the bony structures using daily CBCT, and to validate the planning target
      volume (PTV) margin used in the lung SBRT. All patients underwent 4D CT scanning
      in preparation for lung SBRT. The internal target volume (ITV) was outlined from
      the reconstructed 4D data using the maximum-intensity projection (MIP) algorithm.
      A 6 mm margin was added to the ITV to create the PTV. Conformal treatment
      planning was performed on the helical images, to which the MIP images were fused.
      Prior to each treatment, CBCT was taken after a patient was set up in the
      treatment position. The CBCT images were fused with the simulation CT based on
      the bony anatomy, in order to derive setup errors and separate them from the
      tumor repositional errors. The treating physician then checked and modified the
      alignment based on target relocalization within the PTV. The shifts determined in
      such a method were recorded and the subtractions of these shifts with respect to
      the corresponding setup errors were defined as the target relocalization
      accuracy. Our study of 36 consecutive patients, treating 38 targets for a total
      of 153 fractions shows that, after setup error correction, the target
      repositional accuracy followed a normal distribution with the mean values close
      to 0 in all directions, and standard deviations of 0.25 cm in A-P, 0.24 cm in
      Lat, and 0.28 cm in S-I directions, respectively. The probability of having the
      shifts ? 0.6 cm is less than 0.8% in A-P, 0.6% in Lat, and 1.7 % in S-I
      directions. For the patient population studied, the target centroid position
      relative to the bony structures changed minimally from day to day. This
      demonstrated that the PTV margin that is designed on the MIP image-based ITV was
      adequate for lung SBRT.

PMID- 22402389
TI  - VMAT testing for an Elekta accelerator.
AB  - Volumetric-modulated arc therapy (VMAT) has been shown to be able to deliver
      plans equivalent to intensity-modulated radiation therapy (IMRT) in a fraction of
      the treatment time. This improvement is important for patient
      immobilization/localization compliance due to comfort and treatment duration, as
      well as patient throughput. Previous authors have suggested commissioning methods
      for this modality. Here, we extend the methods reported for the Varian RapidArc
      system (which tested individual system components) to the Elekta linear
      accelerator, using custom files built using the Elekta iComCAT software. We also
      extend the method reported for VMAT commissioning of the Elekta accelerator by
      verifying maximum values of parameters (gantry speed, multileaf collimator (MLC)
      speed, and backup jaw speed), investigating: 1) beam profiles as a function of
      dose rate during an arc, 2) over/under dosing due to MLC reversals, and 3)
      over/under dosing at changing dose rate junctions. Equations for construction of
      the iComCAT files are given. Results indicate that the beam profile for lower
      dose rates varies less than 3% from that of the maximum dose rate, with no
      difference during an arc. The gantry, MLC, and backup jaw maximum speed are
      internally consistent. The monitor unit chamber is stable over the MUs and gantry
      movement conditions expected. MLC movement and position during VMAT delivery are
      within IMRT tolerances. Dose rate, gantry speed, and MLC speed are accurately
      controlled. Over/under dosing at junctions of MLC reversals or dose rate changes
      are within clinical acceptability.

PMID- 22402390
TI  - Assessment of an organ-based tube current modulation in thoracic computed
      tomography.
AB  - Recently, specific computed tomography (CT) scanners have been equipped with
      organ-based tube current modulation (TCM) technology. It is possible that organ
      based TCM will replace the conventional dose-reduction technique of reducing the
      effective milliampere-second. The aim of this study was to determine if organ
      based TCM could reduce radiation exposure to the breasts without compromising the
      image uniformity and beam hardening effect in thoracic CT examinations. Breast
      and skin radiation doses and the absorbed radiation dose distribution within a
      single section were measured with an anthropomorphic phantom and
      radiophotoluminescent glass dosimeters using four approaches to thoracic CT
      (reference, organ-based TCM, copper shielding, and the combination of the above
      two techniques, hereafter referred to as the combination technique). The CT value
      and noise level were measured using the same calibration phantom. Organ-based TCM
      and copper shielding reduced radiation doses to the breast by 23.7% and 21.8%,
      respectively. However, the CT value increased, especially in the anterior region,
      using copper shielding. In contrast, the CT value and noise level barely
      increased using organ-based TCM. The combination technique reduced the radiation
      dose to the breast by 38.2%, but greatly increased the absorbed radiation dose
      from the central to the posterior regions. Moreover, the CT value increased in
      the anterior region and the noise level increased by more than 10% in the entire
      region. Therefore, organ-based TCM can reduce radiation doses to breasts with
      only small increases in noise levels, making it preferable for specific groups of
      patients, such as children and young women.

PMID- 22402391
TI  - Safety limitations of MR-HIFU treatment near interfaces: a phantom validation.
AB  - Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a
      noninvasive image-guided technique used to thermally ablate solid tumors. During
      treatment, ultrasound reflections from distal media interfaces can shift
      prescribed treatment locations. The purpose of this study was to investigate the
      effect of normal incidence reflections from air, acrylic (modeling bone), and
      rubber on treatment location, temperature elevation, and heating patterns by
      performing ultrasound exposures in a tissue-mimicking phantom and in ex vivo
      porcine tissue using a clinical MR-HIFU platform. The results demonstrated a
      shift in treatment location toward the distal interface when targeted closer than
      2 cm from the interface, especially for acrylic. Our study demonstrated that the
      ultrasound wave reflections from a distal air interface had less effect than the
      acrylic interface (modeling bone) on the heating pattern and focal location. This
      study provides useful information to better understand the limitations and safety
      concerns of performing MR-HIFU treatments with commercial clinical equipment.

PMID- 22402392
TI  - A comparison of three commercial IMRT treatment planning systems for selected
      paediatric cases.
AB  - This work aimed at evaluating the performance of three different intensity
      modulated radiotherapy (IMRT) treatment planning systems (TPSs)--KonRad, XiO and
      Prowess--for selected pediatric cases. For this study, 11 pediatric patients with
      different types of brain, orbit, head and neck cancer were selected. Clinical
      step-and-shoot IMRT treatment plans were designed for delivery on a Siemens ONCOR
      accelerator with 82-leaf multileaf collimators (MLCs). Plans were optimized to
      achieve the same clinical objectives by applying the same beam energy and the
      same number and direction of beams. The analysis of performance was based on
      isodose distributions, dose-volume histograms (DVHs) for planning target volume
      (PTV), the relevant organs at risk (OARs), as well as mean dose (Dmean), maximum
      dose (Dmax), 95% dose (D95), volume of patient receiving 2 and 5 Gy, total number
      of segments, monitor units per segment (MU/Segment), and the number of MU/cGy.
      Treatment delivery time and conformation number were two other evaluation
      parameters that were considered in this study. Collectively, the Prowess and
      KonRad plans showed a significant reduction in the number of MUs that varied
      between 1.8% and 61.5% (p-value = 0.001) for the different cases, compared to
      XiO. This was reflected in shorter treatment delivery times. The percentage
      volumes of each patient receiving 2 Gy and 5 Gy were compared for the three TPSs.
      The general trend was that KonRad had the highest percentage volume, Prowess
      showed the lowest (p-value = 0.0001). The KonRad achieved better conformality
      than both of XiO and Prowess. Based on the present results, the three treatment
      planning systems were efficient in IMRT, yet XiO showed the lowest performance.
      The three TPSs achieved the treatment goals according to the internationally
      approved standards.

PMID- 22402395
TI  - Effect of quercetin on inflammatory gene expression in mice liver in vivo - role
      of redox factor 1, miRNA-122 and miRNA-125b.
AB  - The anti-inflammatory properties of the flavonol quercetin have been intensively
      investigated using in vitro cell systems and are to a great extent reflected by
      changes in the expression of inflammatory markers. However, information relating
      to the degree at which quercetin affects inflammatory gene expression in vivo is
      limited. Recently, micro RNAs (miRNAs) have been identified as powerful post
      transcriptional gene regulators. The effect of quercetin on miRNA regulation in
      vivo is largely unknown. Laboratory mice were fed for six weeks with control or
      quercetin enriched high fat diets and biomarkers of inflammation as well as
      hepatic levels of miRNAs previously involved in inflammation (miR-125b) and lipid
      metabolism (miR-122) were determined. We found lower mRNA steady state levels of
      the inflammatory genes interleukin 6, C-reactive protein, monocyte
      chemoattractant protein 1, and acyloxyacyl hydrolase in quercetin fed mice. In
      addition we found evidence for an involvement of redox factor 1, a modulator of
      nuclear factor kappaB signalling, on the attenuation of inflammatory gene
      expression mediated by dietary quercetin. Furthermore, the results demonstrate
      that hepatic miR-122 and miR-125b concentrations were increased by dietary
      quercetin supplementation and may therefore contribute to the gene-regulatory
      activity of quercetin in vivo.

PMID- 22402397
TI  - Evidence for the direct oxidation of organic nitrogen to N2 gas in the Arabian
      Sea.
AB  - We performed a suite of (15)N incubations ((15)NO(2)(-), (15)NO(3)(-) and
      (15)NH(4)(+)) with and without the organic-nitrogen (N) compound allylthiourea
      (ATU), in the suboxic waters of the Arabian Sea. Production of (29)N(2) in
      control (-ATU) incubations with either (15)NH(4)(+)+(14)NO(2)(-), or their
      analogues, (15)NO(2)(-)+(14)NH(4)(+), though small, confirmed the presence of
      anammox. In contrast, when we added ATU, along with (15)NO(2)(-) and
      (14)NH(4)(+), there was a much greater production of (29)N(2), with 92% of the
      (15)N-label being recovered as (29)N(2) on average. Such stimulated production of
      (29)N(2) could not be due to anammox, as the addition of ATU, along with
      (15)NH(4)(+)+(14)NO(2)(-), only produced (29)N(2) equivalent to that in the
      controls. The ratios of (29)N(2) to (30)N(2) produced also precluded stimulation
      of denitrification. We present this as evidence for a hitherto uncharacterised
      metabolism potentially capable of oxidising organic-N (e.g. NH(2) groups)
      directly to N(2) gas at the expense of NO(2)(-).

PMID- 22402396
TI  - Effect of oxygen minimum zone formation on communities of marine protists.
AB  - Changes in ocean temperature and circulation patterns compounded by human
      activities are leading to oxygen minimum zone (OMZ) expansion with concomitant
      alteration in nutrient and climate active trace gas cycling. Here, we report the
      response of microbial eukaryote populations to seasonal changes in water column
      oxygen-deficiency using Saanich Inlet, a seasonally anoxic fjord on the coast of
      Vancouver Island British Columbia, as a model ecosystem. We combine small subunit
      ribosomal RNA gene sequencing approaches with multivariate statistical methods to
      reveal shifts in operational taxonomic units during successive stages of seasonal
      stratification and renewal. A meta-analysis is used to identify common and unique
      patterns of community composition between Saanich Inlet and the anoxic/sulfidic
      Cariaco Basin (Venezuela) and Framvaren Fjord (Norway) to show shared and unique
      responses of microbial eukaryotes to oxygen and sulfide in these three
      environments. Our analyses also reveal temporal fluctuations in rare populations
      of microbial eukaryotes, particularly anaerobic ciliates, that may be of
      significant importance to the biogeochemical cycling of methane in OMZs.
      Eukaryotic 18S rRNA gene sequences recovered from the Saanich Inlet water column
      on were deposited in Genbank under accession numbers HQ864863-HQ871151.

PMID- 22402398
TI  - Archaea in metazoan diets: implications for food webs and biogeochemical cycling.
AB  - Although the importance of trophic linkages, including 'top-down forcing', on
      energy flow and ecosystem productivity is recognized, the influence of metazoan
      grazing on Archaea and the biogeochemical processes that they mediate is unknown.
      Here, we test if: (1) Archaea provide a food source sufficient to allow metazoan
      fauna to complete their life cycle; (2) neutral lipid biomarkers (including
      crocetane) can be used to identify Archaea consumers; and (3) archaeal aggregates
      are a dietary source for methane seep metazoans. In the laboratory, we
      demonstrated that a dorvilleid polychaete, Ophryotrocha labronica, can complete
      its life cycle on two strains of Euryarchaeota with the same growth rate as when
      fed bacterial and eukaryotic food. Archaea were therefore confirmed as a
      digestible and nutritious food source sufficient to sustain metazoan populations.
      Both strains of Euryarchaeota used as food sources had unique lipids that were
      not incorporated into O. labronica tissues. At methane seeps, sulfate-reducing
      bacteria that form aggregations and live syntrophically with anaerobic-methane
      oxidizing Archaea contain isotopically and structurally unique fatty acids (FAs).
      These biomarkers were incorporated into tissues of an endolithofaunal dorvilleid
      polychaete species from Costa Rica (mean bulk delta(13)C=-92+/-40/00; polar
      lipids -1160/00) documenting consumption of archaeal-bacterial aggregates. FA
      composition of additional soft-sediment methane seep species from Oregon and
      California provided evidence that consumption of archaeal-bacterial aggregates is
      widespread at methane seeps. This work is the first to show that Archaea are
      consumed by heterotrophic metazoans, a trophic process we coin as 'archivory'.

PMID- 22402399
TI  - Molecular evidence of iron limitation and availability in the global diazotroph
      Trichodesmium.
AB  - The activity of the N(2)-fixing cyanobacterial genus Trichodesmium is critical to
      the global nitrogen (N) and carbon (C) cycles. Although iron (Fe) has been shown
      to be an important element limiting the growth and N(2) fixation of
      Trichodesmium, there have been no specific data demonstrating the in situ affect
      of Fe on Trichodesmium. We surveyed Trichodesmium populations from the Atlantic
      and Pacific Oceans for Fe limitation using a novel quantitative reverse
      transcriptase-PCR (qRT-PCR) method monitoring the expression of an Fe limitation
      induced gene, isiB. Here we report the first molecular evidence of in situ Fe
      limitation of Trichodesmium N(2) fixation, which was evident in samples from the
      Pacific Ocean, whereas limitation appeared minimal to nonexistent in Atlantic
      Ocean samples. As our method is Trichodesmium clade specific, we were also able
      to determine that representatives from the Trichodesmium tenue clade were the
      most biologically active group of Trichodesmium in the majority of our samples,
      which speaks to their dominance in open ocean regimes. Furthermore, comparisons
      of our field expression and chemical data with laboratory studies suggest that
      the majority of dissolved Fe in the open ocean is available to Trichodesmium
      colonies regardless of Fe complexation.

PMID- 22402400
TI  - Who is who in litter decomposition? Metaproteomics reveals major microbial
      players and their biogeochemical functions.
AB  - Leaf-litter decomposition is a central process in carbon cycling; however, our
      knowledge about the microbial regulation of this process is still scarce.
      Metaproteomics allows us to link the abundance and activity of enzymes during
      nutrient cycling to their phylogenetic origin based on proteins, the 'active
      building blocks' in the system. Moreover, we employed metaproteomics to
      investigate the influence of environmental factors and nutrients on the
      decomposer structure and function during beech litter decomposition. Litter was
      collected at forest sites in Austria with different litter nutrient content.
      Proteins were analyzed by 1-D-SDS-PAGE followed by liquid-chromatography and
      tandem mass-spectrometry. Mass spectra were assigned to phylogenetic and
      functional groups by a newly developed bioinformatics workflow, assignments being
      validated by complementary approaches. We provide evidence that the litter
      nutrient content and the stoichiometry of C:N:P affect the decomposer community
      structure and activity. Fungi were found to be the main producers of
      extracellular hydrolytic enzymes, with no bacterial hydrolases being detected by
      our metaproteomics approach. Detailed investigation of microbial succession
      suggests that it is influenced by litter nutrient content. Microbial activity was
      stimulated at higher litter nutrient contents via a higher abundance and activity
      of extracellular enzymes.

PMID- 22402401
TI  - Ultra-high-throughput microbial community analysis on the Illumina HiSeq and
      MiSeq platforms.
AB  - DNA sequencing continues to decrease in cost with the Illumina HiSeq2000
      generating up to 600 Gb of paired-end 100 base reads in a ten-day run. Here we
      present a protocol for community amplicon sequencing on the HiSeq2000 and MiSeq
      Illumina platforms, and apply that protocol to sequence 24 microbial communities
      from host-associated and free-living environments. A critical question as more
      sequencing platforms become available is whether biological conclusions derived
      on one platform are consistent with what would be derived on a different
      platform. We show that the protocol developed for these instruments successfully
      recaptures known biological results, and additionally that biological conclusions
      are consistent across sequencing platforms (the HiSeq2000 versus the MiSeq) and
      across the sequenced regions of amplicons.

PMID- 22402402
TI  - Ecological niche models reveal the importance of climate variability for the
      biogeography of protosteloid amoebae.
AB  - Habitat availability and environmental preferences of species are among the most
      important factors in determining the success of dispersal processes and therefore
      in shaping the distribution of protists. We explored the differences in
      fundamental niches and potential distributions of an ecological guild of slime
      moulds-protosteloid amoebae-in the Iberian Peninsula. A large set of samples
      collected in a north-east to south-west transect of approximately 1000 km along
      the peninsula was used to test the hypothesis that, together with the existence
      of suitable microhabitats, climate conditions may determine the probability of
      survival of species. Although protosteloid amoebae share similar morphologies and
      life history strategies, canonical correspondence analyses showed that they have
      varied ecological optima, and that climate conditions have an important effect in
      niche differentiation. Maxent environmental niche models provided consistent
      predictions of the probability of presence of the species based on climate data,
      and they were used to generate maps of potential distribution in an 'everything
      is everywhere' scenario. The most important climatic factors were, in both
      analyses, variables that measure changes in conditions throughout the year,
      confirming that the alternation of fruiting bodies, cysts and amoeboid stages in
      the life cycles of protosteloid amoebae constitutes an advantage for surviving in
      a changing environment. Microhabitat affinity seems to be influenced by climatic
      conditions, which suggests that the micro-environment may vary at a local scale
      and change together with the external climate at a larger scale.

PMID- 22402403
TI  - Plant litter and soil type drive abundance, activity and community structure of
      alkB harbouring microbes in different soil compartments.
AB  - Alkanes are major constituents of plant-derived waxy materials. In this study, we
      investigated the abundance, community structure and activity of bacteria
      harbouring the alkane monooxygenase gene alkB, which catalyses a major step in
      the pathway of aerobic alkane degradation in the litter layer, the litter-soil
      interface and in bulk soil at three time points during the degradation of maize
      and pea plant litter (2, 8 and 30 weeks) to improve our understanding about
      drivers for microbial performance in different soil compartments. Soil cores of
      different soil textures (sandy and silty) were taken from an agricultural field
      and incubated at constant laboratory conditions. The abundance of alkB genes and
      transcripts (by qPCR) as well as the community structure (by terminal restriction
      fragment polymorphism fingerprinting) were measured in combination with the
      concentrations and composition of alkanes. The results obtained indicate a clear
      response pattern of all investigated biotic and abiotic parameters depending on
      the applied litter material, the type of soil used, the time point of sampling
      and the soil compartment studied. As expected the distribution of alkanes of
      different chain length formed a steep gradient from the litter layer to the bulk
      soil. Mainly in the two upper soil compartments community structure and abundance
      patterns of alkB were driven by the applied litter type and its degradation.
      Surprisingly, the differences between the compartments in one soil were more
      pronounced than the differences between similar compartments in the two soils
      studied. This indicates the necessity for analysing processes in different soil
      compartments to improve our mechanistic understanding of the dynamics of distinct
      functional groups of microbes.

PMID- 22402404
TI  - Redox and photoisomerization switching of the second-order optical nonlinearity
      of a tetrathiafulvalene derivative of spiropyran across five states: a DFT study.
AB  - Second-order nonlinear optical properties of a tetrathiafulvalene (TTF)
      derivative of spiropyran have been studied based on density functional theory
      (DFT) combined with the finite field (FF) calculations. Our DFT-FF calculations
      confirm a switching behavior of the static first hyperpolarizability caused by
      the redox and photochromic reaction. The photochromic reaction generates
      spiropyran-merocyanine conversion by reversible cleavage of the C-O bond, which
      is relative to the close- and open-ring forms 1-c and 1-o. The open-ring form 1-o
      displays the large static first hyperpolarizability relative to its close-ring
      form 1-c according to our DFT-FF calculations with three functionals. The
      electronic structure analysis and spin unrestricted calculations show that the
      redox processes significantly affect the geometrical structure of the TTF unit,
      and thus enhance the static first hyperpolarizabilities. The one-electron
      oxidized species having good planar structure of the TTF unit are ~30 and ~200
      times as large as that of the neutral compounds 1-c and 1-o, respectively. But
      the difference in the static first hyperpolarizability between one- and two
      electron-oxidized states of spiropyran species is not substantial according to
      our DFT-FF calculations, and the spiropyran-merocyanine conversion of two
      electron-oxidized species does not largely affect their static first
      hyperpolarizability. On the basis of the large change in the static first
      hyperpolarizability, our DFT-FF calculations support a five-state switching of
      the static first hyperpolarizability based on the redox and photoisomerization.

PMID- 22402405
TI  - Type and prevalence of adverse events during the parenteral nutrition cycling
      process in patients being prepared for discharge.
AB  - BACKGROUND: The mechanism for cycling parenteral nutrition (PN) varies from
      institution to institution. However, the types and frequency of adverse events
      (AEs) involved with this process are not well understood. PURPOSE: To determine
      the type and prevalence of AE in patients during PN cycling and identify factors
      associated with the occurrence of AEs. METHODS: Patients without severe organ
      dysfunction or uncontrolled diabetes mellitus scheduled to be discharged on
      cyclic PN with a goal of 12 hours were eligible. Patients were cycled from 24 to
      12 hours over 2 or 3 days based on previously established criteria. Demographic,
      nutrition, and monitoring data were collected. AEs were documented and graded as
      mild or serious. RESULTS: Mild AEs occurred in 35 of 38 patients (92.1%)
      consisting primarily of mild hyperglycemia (86.8%) and tachycardia (29.0%).
      Serious AEs occurred in 8 of 38 patients (21.1%), including 7 patients (18.4%)
      with capillary blood glucoses between 255 and 324 mg/dL and 1 (2.6%) with
      tachypnea/tachycardia requiring immediate medical attention. No significant
      associations were made between demographic, medical, nutrition, or laboratory
      factors and serious AEs. No significant differences in demographic information,
      nutrition information, comorbidities, diet, medications, or composition of PN
      were found except for lower body weight in unsuccessful cyclers compared with
      successful cyclers (P = .042). CONCLUSIONS: Most patients incur AEs during PN
      cycling, primarily mild hyperglycemia and tachycardia. These findings suggest
      patients need to be monitored closely and treated aggressively for complications
      during PN cycling.

PMID- 22402406
TI  - Targeting the intestinal microbiota in the pediatric population: a clinical
      perspective.
AB  - The intestinal microbiota is a functional organ with a variety of important
      metabolic, trophic, immunologic, and digestive activities. Current data suggest
      that alterations in the intestinal microbiota may be related to disease
      conditions. Manipulation of the intestinal microbiota such as with probiotics,
      prebiotics, and synbiotics may be beneficial in preventing and treating certain
      disease conditions. This article provides an overview of the evidence gathered
      through randomized clinical trials, reviews, and meta-analyses on probiotics and
      prebiotics in commonly studied conditions in the pediatric population. It
      concludes with current recommendations for their use, noting safety and gaps in
      clinical evidence.

PMID- 22402407
TI  - Beneficial effects of long-term consumption of a probiotic combination of
      Lactobacillus casei Shirota and Bifidobacterium breve Yakult may persist after
      suspension of therapy in lactose-intolerant patients.
AB  - BACKGROUND: The efficacy of some probiotic strains for the management of lactose
      intolerance remains to be established. AIM: To evaluate the effects of a 4-week
      consumption of a probiotic product containing Lactobacillus casei Shirota and
      Bifidobacterium breve Yakult (10(7)-10(9) CFU of each strain) on symptoms and
      breath hydrogen exhalation after a lactose load in lactose-intolerant patients
      and whether the beneficial results persisted after probiotic discontinuation.
      METHODS: Twenty-seven patients with lactose maldigestion and intolerance
      participated in this study, which comprised 4 hydrogen breath tests: baseline
      condition (20 g lactose), after lactase ingestion (9000 FCC units), at the end of
      4-week probiotic supplementation, and a follow-up test performed 3 months after
      probiotic discontinuation. For each test, the area under the breath hydrogen
      concentration vs time curve (AUC(180 min)) was calculated, and symptom scores
      were recorded. RESULTS: The probiotic combination significantly reduced symptom
      scores (P < .01) and breath hydrogen AUC (P = .04) compared with the baseline
      condition. The comparison with the lactase test showed that symptom scores were
      similar (P > .05), despite the significantly higher (P = .01) AUC values after
      probiotic use. In the follow-up test, symptom scores and breath hydrogen AUC
      values remained similar to those found at the end of probiotic intervention.
      CONCLUSION: Four-week consumption of a probiotic combination of L casei Shirota
      and B breve Yakult seems to improve symptoms and decrease hydrogen production
      intake in lactose-intolerant patients. These effects may persist for at least 3
      months after suspension of probiotic consumption.

PMID- 22402408
TI  - A retrospective correlation of percutaneous feeding tube stoma length in sitting
      and supine positions compared with body mass index.
AB  - BACKGROUND: Accurate knowledge of stoma tract length is important to prevent
      gastric ulcer formation, buried bumper syndrome, and peristomal
      leakage/infection. Current guidelines suggest 0.5-1.0 cm of play between the skin
      and external bolster. The aim of this study was to determine if stoma tract
      length changes from supine and sitting position and if this change is related to
      BMI. METHODS: Patients undergoing percutaneous feeding tube change from November
      2006 to September 2009 were enrolled. Correlations were made between BMI and
      stoma tract length in both sitting and supine positions. RESULTS: Twenty-eight
      patients (24 percutaneous endoscopic gastrostomy [PEG], 4 direct percutaneous
      jejunal feeding tube) were included; 19 (68%) were female. The mean +/- SD stoma
      length was 3.6 +/- 0.9 cm in the supine position and 4.9 +/- 1.4 cm in the
      sitting position. The mean +/- SD stoma length change from supine to sitting
      position was 1.53 +/- 0.9 cm. Mean +/- SD BMI was 21.2 +/- 4.5 (range, 14.9
      33.8). Stoma length in the supine position (r = 0.65, P = .0002) and sitting
      position (r = 0.6, P = .0009) was strongly correlated with BMI. Change in stoma
      tract length was correlated with BMI (r = 0.43, P = .02). CONCLUSION: Stoma tract
      length is strongly correlated with BMI in both the sitting and supine positions.
      PEG stoma tract length changes significantly from the supine and sitting
      position. To prevent complications, most patients should have a longer distance
      set between internal and external bolsters than is recommended.

PMID- 22402409
TI  - Synthesis, characterization, and antimicrobial activity of silver carbene
      complexes derived from 4,5,6,7-tetrachlorobenzimidazole against antibiotic
      resistant bacteria.
AB  - Silver N-heterocyclic carbene complexes have been shown to have great potential
      as antimicrobial agents, affecting a wide spectrum of both Gram-positive and Gram
      negative bacteria. A new series of three silver carbene complexes (SCCs) based on
      4,5,6,7-tetrachlorobenzimidazole has been synthesized, characterized, and tested
      against a panel of clinical strains of bacteria. The imidazolium salts and their
      precursors were characterized by elemental analysis, mass spectrometry, (1)H and
      (13)C NMR spectroscopy, and single crystal X-ray diffraction. The silver carbene
      complexes, SCC32, SCC33, and SCC34 were characterized by elemental analysis, (1)H
      and (13)C NMR spectroscopy, and single crystal X-ray diffraction. These complexes
      proved highly efficacious with minimum inhibitory concentrations (MICs) ranging
      from 0.25 to 6 MUg mL(-1). Overall, the complexes were effective against highly
      resistant bacteria strains, such as methicillin-resistant Staphylococcus aureus
      (MRSA), weaponizable bacteria, such as Yersinia pestis, and pathogens found
      within the lungs of cystic fibrosis patients, such as Pseudomonas aeruginosa,
      Alcaligenes xylosoxidans, and Burkholderia gladioli. SCC33 and SCC34 also showed
      clinically relevant activity against a silver-resistant strain of Escherichia
      coli based on MIC testing.

PMID- 22402410
TI  - Capturing significant events with neural networks.
AB  - Smartphone video capture and transmission to the Web contributes to data
      pollution. In contrast, mammalian eyes sense all, capture only significant
      events, allowing us vividly recall the causalities. Likewise in our videos, we
      wish to skip redundancies and keep only significantly differences, as determined
      by real-time local medium filters. We construct a Picture Index (PI) of one's
      (center of gravity changes) among zeros (no changes) as Motion Organized
      Sparseness (MOS). Only non-overlapping time-ordered PI pair is admitted in the
      outer-product Associative Memory (AM). Another outer product between PI and its
      image builds Hetero-AM (HAM) for fault tolerant retrievals.

PMID- 22402411
TI  - The kinetics and regulation of phosphofructokinase from Teladorsagia
      circumcincta.
AB  - Phosphofructokinase (PFK-1) activity was examined in L(3) and adult Teladorsagia
      circumcincta, both of which exhibit oxygen consumption. Although activities were
      higher in the adult stage, the kinetic properties of the enzyme were similar in
      both life cycle stages. T. circumcincta PFK-1 was subject to allosteric
      inhibition by high ATP concentration, which increased both the Hill coefficient
      (from 1.4+/-0.2 to 1.7+/-0.2 in L(3)s and 2.0+/-0.3 to 2.4+/-0.4 in adults) and
      the K(1/2) for fructose 6 phosphate (from 0.35+/-0.02 to 0.75+/-0.05mM in L(3)s
      and 0.40+/-0.03 to 0.65+/-0.05mM in adults). The inhibitory effects of high ATP
      concentration could be reversed by fructose 2,6 bisphosphate and AMP, but glucose
      1,6 bisphosphate had no effect on activity. Similarly, phosphoenolpyruvate had no
      effect on activity, while citrate, isocitrate and malate exerted mild inhibitory
      effects, but only at concentrations exceeding 2mM. The observed kinetic
      properties for T. circumcincta PFK-1 were very similar to those reported for
      purified Ascaris suum PFK-1, though slight differences in sensitivity to ATP
      concentration suggests there may be subtle variations at the active site. These
      results are consistent with the conservation of properties of PFK-1 amongst
      nematode species, despite between species variation in the ability to utilise
      oxygen.

PMID- 22402412
TI  - Belief inhibition in children's reasoning: memory-based evidence.
AB  - Adult reasoning has been shown as mediated by the inhibition of intuitive beliefs
      that are in conflict with logic. The current study introduces a classic procedure
      from the memory field to investigate belief inhibition in 12- to 17-year-old
      reasoners. A lexical decision task was used to probe the memory accessibility of
      beliefs that were cued during thinking on syllogistic reasoning problems. Results
      indicated an impaired memory access for words associated with misleading beliefs
      that were cued during reasoning if syllogisms had been solved correctly. This
      finding supports the claim that even for younger reasoners, correct reasoning is
      mediated by inhibitory processing as soon as intuitive beliefs conflict with
      logical considerations.

PMID- 22402413
TI  - Identification of cis-regulatory elements specific for different types of
      reactive oxygen species in Arabidopsis thaliana.
AB  - The type of reactive oxygen species (ROS) is a major factor that determines the
      specificity of biological responses. These responses may be elicited by
      activation of transcription factors that recognize ROS-specific cis-regulatory
      elements in target genes. In search for Arabidopsis promoter motifs specific for
      particular types of ROS, genome-wide microarray expression profiles for 283
      abiotic stress-related conditions were subjected to cluster analysis to identify
      gene groups induced by singlet oxygen, superoxide radicals, and H(2)O(2).
      Promoters of these gene groups were analyzed to identify cis-regulatory elements
      that are associated with specific types of ROS. Eleven ROS-specific de novo
      identified elements, seven known promoter motifs and several sequences enriched
      in ROS-responsive clusters but lacking in specificity are reported. The
      conservation of the identified motifs was determined in orthologous genes in C.
      papaya, V. vinifera and P. trichocarpa. Finally, biological functions were
      attributed to the motifs by calculation of GO-term enrichment for genes with
      conserved ROS-responsive elements.

PMID- 22402414
TI  - [Usefulness of multilevel analysis of satisfaction questionnaires on clinical
      units and medical specialties].
AB  - OBJECTIVES: Evaluate the usefulness of multilevel analysis applied to
      satisfaction surveys to assess the ambulatory care offered by the Clinical Units
      and Medical Specialties. METHODS: Telephone surveys were conducted on 6,922
      patients seen in outpatient visits in the Navarra Health System in order to
      assess 94 Clinical Units and 37 Medical Specialties. A hierarchical analysis was
      then performed at 3 levels (patients, Clinical Units and Medical Specialties).
      RESULTS: The patient explained between 91.7% and 99.3% of the variability in the
      satisfaction survey scores. The patient perception of service quality also
      depends of the clinical unit, in 18 out of 20 items analysed, the variance
      related to the Clinical Unit was statistically significant, and ranged from 0.9%
      and 8.3%. The Medical Specialty explained 4.2% of the variability in only one
      item. Patients aged under 65 years, patients seen in first visit, and those who
      were seen at tertiary hospitals gave the lowest scores. CONCLUSIONS: Multilevel
      analysis is a useful tool to analyse and compare satisfaction survey results, as
      it can correctly distinguish the different Clinical Units of a health service,
      and this is a key element in the management of these Units. Moreover, it gives
      the percentage of variability due to each level and which variables predict the
      quality of service obtained.

PMID- 22402415
TI  - [Development and validation of a patient satisfaction questionnaire on
      pharmaceutical care in community pharmacies].
AB  - OBJECTIVE: To develop and validate a rapid administration questionnaire to assess
      patient satisfaction with the pharmaceutical care (PhC) service in Spanish
      community pharmacies. METHODS: A semi-structured and self-administered
      questionnaire was designed focused on the cumulative experience of patients with
      the PhC service. This was reviewed by a panel of 8 experts in 2 rounds. The
      validation was carried out in community pharmacies that performed the PhC service
      and agreed to participate. All patients or their caregivers who attended a
      pharmacy during the study period, and who could read and write, were included. An
      exploratory factor analysis was performed to assess the validity as evidence of
      internal structure and reliability was estimated using Cronbach's alpha
      coefficient. RESULTS: A total of 8 community pharmacies belonging to 7 provinces
      of Spain took part and 103 questionnaires were obtained. Factor analysis revealed
      a single component explaining 33.6% of the total variance. We obtained a
      Cronbach's alpha coefficient of 0.75. Patients additional comments expressed in
      9.7% of the questionnaires were related to emphasising, and thanking for, the
      care provided by the PhC service. CONCLUSIONS: The questionnaire developed has
      provided evidence of content validity, internal structure validity, and
      reliability to assess the patient satisfaction with the PhC service in Spanish
      community pharmacies.

PMID- 22402416
TI  - A case of a sural neuroma as a cause of lateral ankle pain.
AB  - This article reviews the diagnosis, pathology, and treatment of a lateral ankle
      (sural) neuroma. Though there have been vague references to neuroma of the sural
      nerve, no specific case report has been presented. It is felt that mechanical and
      biomechanical factors may contribute to the formation of this type of painful
      mass which warrants further discussion as an additional etiology of lateral ankle
      pain. In this article, we describe a case of neuroma of the sural nerve which was
      unresponsive to conservative treatments.

PMID- 22402417
TI  - Comparison of two-dimensional and real-time three-dimensional transesophageal
      echocardiography in the assessment of aortic valve area.
AB  - BACKGROUND: The accuracy of two-dimensional transesophageal echocardiography (2D
      TEE) for the measurement of aortic valve area (AVA) in patients with aortic
      stenosis (AS) depends upon the cross-section selected for imaging. Real-time
      three-dimensional transesophageal echocardiography (3D-TEE) may overcome this
      limitation of 2D-TEE. The goal of this study was to compare 3D-TEE with 2D-TEE
      for the measurement of AVA. METHODS AND RESULTS: Twenty-five patients with AS
      underwent TEE. In 2D-TEE, the aortic valve image was obtained at the orifice
      level in the short-axis view, and AVA was measured by planimetry of the acquired
      images (2D-AVA). In 3D-TEE, 3D data containing the entire aortic valve were
      obtained. Then, a short-axis cross-section containing the smallest orifice in mid
      systole was cut from the 3D data during image postprocessing, and the AVA was
      measured by planimetry (3D-AVA). The 3D-AVA was significantly smaller than the 2D
      AVA (0.79+/-0.35cm(2) vs. 0.93+/-0.40cm(2), p<0.0001), but there was a strong
      correlation between 3D-AVA and 2D-AVA (R=0.94). Although the frame rate was lower
      in 3D-TEE than in 2D-TEE (17+/-6Hz vs. 58+/-16Hz), the 3D-AVA determined at each
      frame during systole showed that the difference between 3D-AVA and 2D-AVA was not
      explained by the lower frame rate. The time required for image acquisition of the
      aortic valve was shorter with 3D-TEE than with 2D-TEE (p=0.0005). CONCLUSIONS:
      The geometric AVA is smaller with 3D-TEE than with 2D-TEE, and the difference is
      not due to the lower frame rate of 3D-TEE. The improved accuracy of 3D-TEE along
      with reduced image acquisition time indicates that 3D-TEE is superior to 2D-TEE
      for the assessment of AVA.

PMID- 22402418
TI  - Immediate administration of atorvastatin decreased the serum MMP-2 level and
      improved the prognosis for acute heart failure.
AB  - BACKGROUND AND PURPOSE: We have reported that matrix metalloproteinase-2 (MMP-2)
      increased in acute heart failure (AHF) and better prognosis was found in patients
      with greater reduction in MMP-2. We assessed whether a statin decreased MMP-2 in
      AHF. METHODS AND RESULTS: The serum MMP-2 levels were measured on admission (Day
      1), Day 3, Day 7, and Day 14 in 50 AHF patients. The patients were randomized to
      either atorvastatin (n=25) or control group (n=25). Atorvastatin (10-20mg/day)
      was started within 12h after their admission and then was continued for two
      weeks. There were no differences in the serum levels of MMP-2 on Day 1 between
      atorvastatin group (1400.4+/-318.6ng/ml) and control group (1292.7+/-384.7ng/ml).
      MMP-2 significantly decreased in both groups on Day 3, 7, and 14. However, the
      MMP-2 value on Day 3 compared to Day 1 was observed to have decreased
      significantly in atorvastatin group (561.8+/-235.1ng/ml) compared to control
      group (272.6+/-270.6ng/ml; p=0.001). HF events which were defined as death from
      HF, readmission to hospital for HF, or prolonged hospital stay because of
      uncontrollable HF, occurred more in control group than in atorvastatin group.
      Kaplan-Meier curves showed that the prognosis of HF was significantly better in
      atorvastatin group as compared with control group (log-rank test, p=0.037).
      CONCLUSION: In addition to conventional HF therapy, an early start of
      atorvastatin caused a great decrease in MMP-2 and also improved HF events in AHF.

PMID- 22402419
TI  - Arrhythmia and sleep-disordered breathing in patients undergoing cardiac surgery.
AB  - BACKGROUND: Recently, the role of sleep-disordered breathing (SDB) in
      cardiovascular disease has attracted attention. In this study, we investigated
      the influence of SDB on postoperative arrhythmias after cardiac surgery. METHODS
      AND RESULTS: In 89 patients undergoing cardiac surgery, postoperative portable
      monitoring for SDB and Holter electrocardiography were performed. The primary end
      points were the apnea-hypopnea index (AHI) and occurrence of arrhythmia. The
      secondary end-points were: (1) patient background factors; (2) average heart
      rate; (3) maximum heart rate (total, daytime, and nighttime); (4) minimum heart
      rate (total, daytime, and nighttime); (5) minimum SaO(2) during sleep; and (6) an
      independent predictor for arrhythmia. Twenty-six patients (29.2%) had an AHI>=15
      and they were classified into the SDB group, while patients with an AHI<15 formed
      the non-SDB group (70.8%). Although there was no significant difference in atrial
      fibrillation, frequent nocturnal premature ventricular contractions were
      significantly more common in the SDB group (19.2%) than the non-SDB group (3.2%)
      (p=0.01). Maximum daytime and nighttime heart rates were also significantly
      higher in the SDB group. AHI was a significant predictor for frequent nocturnal
      premature ventricular contractions. CONCLUSIONS: This study showed that SDB is
      common among patients undergoing cardiac surgery, and that SDB might be closely
      associated with arrhythmia in these patients.

PMID- 22402420
TI  - Low cardiometabolic risk in Parkinson's disease is independent of nutritional
      status, body composition and fat distribution.
AB  - BACKGROUND & AIMS: To investigate if the reduced cardiometabolic risk in
      Parkinson's disease (PD) is independent of nutritional status, body composition
      and fat distribution. METHODS: We designed a case-control study comparing 80 non
      underweight PD patients with 80 controls matched for sex, age and body mass index
      (BMI). Nutritional assessment included: anthropometry (BMI and waist
      circumference [WC]), body composition estimated by impedance and biochemistry
      (fasting glucose, serum lipids and transaminases). The presence of arterial
      hypertension, diabetes mellitus and metabolic syndrome (MetS) were noted.
      RESULTS: Compared to controls and independently of gender, PD patients showed
      lower percentage of body fat (P < 0.001) and biochemical parameters (glucose, P <
      0.001; total cholesterol, P < 0.001; LDL, P < 0.001; triglycerides, P = 0.002;
      alanine aminotransferase, P < 0.001 and aspartate aminotransferase, P = 0.015)
      but similar WC (P = 0.324). The prevalence of hypertension and MetS was similar
      in the two groups, as well as the frequency and the number of MetS criteria. The
      relationship between PD and low cardiometabolic profile was independent of age,
      gender, current smoking and BMI. After adjusting for WC and body fat, most of the
      associations remained significant. CONCLUSIONS: PD patients seem to have a more
      favorable cardiometabolic risk profile, independently of nutritional status, body
      composition and fat distribution.

PMID- 22402421
TI  - Central venous catheter related sepsis in children on parenteral nutrition: a 21
      year single-center experience.
AB  - BACKGROUND & AIMS: The aim was to assess the rate of central venous catheter
      (CVC) related sepsis in patients on parenteral nutrition (PN) at our hospital
      center during a period of 21 years. METHODS: Data on all children hospitalized at
      our tertiary hospital center during the 1989-2010 period, who received PN for
      more than 4 weeks (n = 62) were retrospectively analyzed. RESULTS: The mean age
      at the time of introducing PN was 2.9 years (range 6 days-17.4 years),
      male/female ratio 26/36. Out of these 62 patients, nine (14.5%) patients
      continued home PN (HPN) after discharge from the hospital. Altogether 86 CVCs
      were used (mean 1.39 per patient) and total CVC time was 21,459 days, which makes
      243.9 days per CVC. During the study period, there were 36 CVC related sepsis
      episodes (1.7/1000 days of PN). Total number of septic episodes was significantly
      lower in HPN compared to hospital PN (0.94/1000 vs. 2.75/1000 days of PN; P <
      0.001). Septic episodes led to removal of 11 (12.8%) catheters. Two patients died
      due to CVC related septic shock (0.93 deaths/10,000 days of PN), one in HPN
      patient (0.79 per 10,000 days of HPN). CONCLUSION: The rate of CVC related sepsis
      in our PN cohort was exceptionally low in both hospital and home setting.

PMID- 22402422
TI  - Letter from the editor.

PMID- 22402423
TI  - Radon and lung cancer.
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide. Radon
      exposure is the second leading cause of lung cancer, following tobacco smoke.
      Radon is not only an independent risk factor; it also increases the risk of lung
      cancer in smokers. Numerous cohort, case-control, and experimental studies have
      established the carcinogenic potential of radon. The possibility of radon having
      a causative effect on other cancers has been explored but not yet proven. One of
      the postulated mechanisms of carcinogenesis is DNA damage by alpha particles
      mediated by the production of reactive oxygen species. The latter are also
      thought to constitute one of the common mechanisms underlying the synergistic
      effect of radon and tobacco smoke. With an estimated 21,000 lung cancer deaths
      attributable to radon in the United States annually, the need for radon
      mitigation is well acknowledged. The Environmental Protection Agency (EPA) has
      established an indoor limit of 4 picocuries (pCi)/L, and various methods are
      available for indoor radon reduction when testing shows higher levels. Radon
      mitigation should accompany smoking cessation measures in lung cancer prevention
      efforts.

PMID- 22402424
TI  - Advances in the systemic treatment of leptomeningeal cancer.
AB  - Leptomeningeal cancer (LMC), which refers to involvement of the cerebrospinal
      fluid by cancer cells, is a poor prognostic sign that complicates various solid
      malignancies. Treatment of LMC evolved around brain radiation, intrathecal
      therapy, and systemic chemotherapy, but response rates are unsatisfactory, and
      patients usually die from cancer progression. In this article, we review the
      history of the major therapeutic approaches used to treat LMC, and we expand on
      the promising new venues for applying biologic targeted agents to the treatment
      options utilized in LMC.

PMID- 22402425
TI  - Risk of early death in multiple myeloma.

PMID- 22402426
TI  - Abiraterone: current and future use in prostate cancer.

PMID- 22402427
TI  - A preventive approach to the management of severe hemophilia A.

PMID- 22402428
TI  - Emerging nontaxane therapies for metastatic breast cancer.

PMID- 22402429
TI  - Rosai-Dorfman disease with central nervous system involvement.

PMID- 22402430
TI  - Rosai-Dorfman disease: management of CNS and systemic involvement.

PMID- 22402431
TI  - Complete remission in 4 patients with human herpesvirus 8-associated multicentric
      Castleman disease using rituximab and liposomal doxorubicin, a novel chemotherapy
      combination.

PMID- 22402432
TI  - What Is the best treatment for HIV-associated multicentric Castleman disease?

PMID- 22402433
TI  - Structures, energetics and vibrational spectra of CO2 clusters through molecular
      tailoring and cluster building algorithm.
AB  - Clusters of CO(2) are a subject of detailed experimental as well as theoretical
      investigations due to their interesting applications. In the present article,
      CO(2) clusters (n = 6 to 13) are studied at the MP2 level of theory. The clusters
      are grown using a cluster building algorithm developed by our group and the
      larger ones are optimized at the MP2/aug-cc-pVDZ level by employing a Molecular
      Tailoring Approach (MTA). Vibrational spectra of these clusters are also
      calculated at this level of theory within MTA. The computed vibrational
      frequencies for an asymmetric C-O stretch generally exhibit a blue shift with
      increasing cluster size. This observation is in agreement with the experimental
      results. MTA-single point energies for each cluster size at the MP2/aug-cc-pVTZ
      level are also calculated for estimating the interaction energies at the complete
      basis set limit.

PMID- 22402435
TI  - Estrogen activates matrix metalloproteinases-2 and -9 to increase beta amyloid
      degradation.
AB  - Estrogen is known to affect different aspects of beta-amyloid (Abeta) synthesis
      and degradation. The present work was undertaken to evaluate specifically whether
      matrix metalloproteinases (MMP) -2 and -9 are involved in Abeta degradation
      induced by estrogen and whether this is relevant to estrogen-induced
      neuroprotection. In SH-SY5Y human neuroblastoma cells, 10 nM 17beta-estradiol
      (17beta-E2) increases mRNA and intracellular protein expression of MMP-2 and -9,
      as well as the levels of the active forms of both enzymes released in the medium.
      Specificity of the effect is proved by prevention with the estrogen receptor (ER)
      antagonist ICI 182,780 (1 MUM) and involvement of the ERalpha subtype is
      confirmed by the use of selective ERalpha or ERbeta agonists (PPT, DPN) and
      antagonists (MPP, PHTPP). 17beta-E2 significantly increases the degradation of
      Abeta, either transferred with the conditioned medium of H4-APPSw human
      neuroglioma cells, engineered to overproduce Abeta(1-40) and Abeta(1-42), or
      exogenously added as 2 MUM Abeta(1-42). Both these effects are completely
      prevented by preexposure to the broad spectrum MMP inhibitor GM6001 (5 MUM).
      Importantly, the 17beta-E2-induced rescue of neuroblastoma cells challenged with
      2 MUM Abeta(1-42), an effect prevented by ICI 182,780 (1 MUM), is mediated by
      MMPs, as it appears significantly reduced by GM6001 (5 MUM) as well as by both
      MMP-2 (200 nM) and MMP-9 (200nM) selective inhibitors. In conclusion, the present
      study shows for the first time that MMP-2 and -9 give a main contribution to
      estrogen's neuroprotective effect.

PMID- 22402434
TI  - Current concepts for anterior cruciate ligament reconstruction: a criterion-based
      rehabilitation progression.
AB  - The management of patients after anterior cruciate ligament reconstruction should
      be evidence based. Since our original published guidelines in 1996, successful
      outcomes have been consistently achieved with the rehabilitation principles of
      early weight bearing, using a combination of weight-bearing and non-weight
      bearing exercise focused on quadriceps and lower extremity strength, and meeting
      specific objective requirements for return to activity. As rehabilitative
      evidence and surgical technology and procedures have progressed, the original
      guidelines should be revisited to ensure that the most up-to-date evidence is
      guiding rehabilitative care. Emerging evidence on rehabilitative interventions
      and advancements in concomitant surgeries, including those addressing chondral
      and meniscal injuries, continues to grow and greatly affect the rehabilitative
      care of patients with anterior cruciate ligament reconstruction. The aim of this
      article is to update previously published rehabilitation guidelines, using the
      most recent research to reflect the most current evidence for management of
      patients after anterior cruciate ligament reconstruction. The focus will be on
      current concepts in rehabilitation interventions and modifications needed for
      concomitant surgery and pathology. LEVEL OF EVIDENCE: Therapy, level 5.

PMID- 22402436
TI  - Foxp3+ cells control Th2 responses in a murine model of atopic dermatitis.
AB  - The role of Foxp3+ regulatory T (Treg) cells in atopic dermatitis (AD) is still
      unclear. In a murine AD model, the number of Foxp3+ cells increased in the
      allergen-exposed skin area and in the secondary lymphoid organs. Both Foxp3+ and
      Foxp3- IL-10+ T cells accumulated at the site of allergen exposure, and CD103+
      effector/memory Foxp3+ Treg cells expanded gradually in the lymph nodes
      throughout the sensitization protocol. The depletion of Foxp3+ Treg cells led to
      significantly exacerbated skin inflammation, including increased recruitment of
      inflammatory cells and expression of T helper type 2 cytokines, as well as
      elevated serum IgE levels. The effect of depleting Treg cells during epicutaneous
      sensitization was mirrored off by a stronger inflammatory response also in the
      lungs following airway challenge. Thus, Treg cells have an important role in
      controlling AD-like inflammation and the transfer of allergic skin inflammation
      to the lungs.

PMID- 22402437
TI  - Thymic peptides differentially modulate human hair follicle growth.

PMID- 22402439
TI  - Next-generation DNA re-sequencing identifies common variants of TYR and HLA-A
      that modulate the risk of generalized vitiligo via antigen presentation.

PMID- 22402438
TI  - AIM1 and LINE-1 epigenetic aberrations in tumor and serum relate to melanoma
      progression and disease outcome.
AB  - Aberrations in the methylation status of noncoding genomic repeat DNA sequences
      and specific gene promoter region are important epigenetic events in melanoma
      progression. Promoter methylation status in long interspersed nucleotide element
      1 (LINE-1) and absent in melanoma-1 (AIM1; 6q21) associated with melanoma
      progression and disease outcome was assessed. LINE-1 and AIM1 methylation status
      was assessed in paraffin-embedded archival tissue (PEAT; n = 133) and in melanoma
      patients' serum (n = 56). LINE-1 U-Index (hypomethylation) and AIM1 were analyzed
      in microdissected melanoma PEAT sections. The LINE-1 U-Index of melanoma (n =
      100) was significantly higher than that of normal skin (n = 14) and nevi (n = 12;
      P = 0.0004). LINE-1 U-Index level was elevated with increasing American Joint
      Committee on Cancer (AJCC) stage (P<0.0001). AIM1 promoter hypermethylation was
      found in higher frequency (P = 0.005) in metastatic melanoma (65%) than in
      primary melanomas (38%). When analyzed, high LINE-1 U-Index and/or AIM1
      methylation in melanomas were associated with disease-free survival (DFS) and
      overall survival (OS) in stage I/II patients (P = 0.017 and 0.027, respectively).
      In multivariate analysis, melanoma AIM1 methylation status was a significant
      prognostic factor of OS (P = 0.032). Furthermore, serum unmethylated LINE-1 was
      at higher levels in both stage III (n = 20) and stage IV (n = 36) patients
      compared with healthy donors (n = 14; P = 0.022). Circulating methylated AIM1 was
      detected in patients' serum and was predictive of OS in stage IV patients (P =
      0.009). LINE-1 hypomethylation and AIM1 hypermethylation have prognostic utility
      in both melanoma patients' tumors and serum.

PMID- 22402441
TI  - Vitamin D analog calcipotriol suppresses the Th17 cytokine-induced
      proinflammatory S100 "alarmins" psoriasin (S100A7) and koebnerisin (S100A15) in
      psoriasis.
AB  - The antimicrobial peptides (AMP) psoriasin (S100A7) and koebnerisin (S100A15) are
      differently induced in psoriatic skin. They act synergistically as
      chemoattractants and "alarmins" to amplify inflammation in psoriasis. Th17
      cytokines are key players in psoriasis pathogenesis and vitamin D analogs feature
      anti-psoriatic effects; both of these activities could be mediated through
      epidermal AMP regulation. We show that supernatants of cultured psoriatic T cells
      induce and release psoriasin and koebnerisin from keratinocytes and the Th17
      cytokines IL-17A, tumor necrosis factor-alpha, and IL-22 differently regulate
      psoriasin and koebnerisin reflecting their distinct expression pattern in normal
      and psoriatic skin. IL-17A is the principal inducer of both S100 and their
      expression is further amplified by cooperating Th17 cytokines in the micromilieu
      of psoriatic skin. Increased extracellular psoriasin and koebnerisin also
      synergize as "alarmins" to prime epidermal keratinocytes for production of
      immunotropic cytokines that further amplify the inflammatory response. Treatment
      of psoriatic plaques with the vitamin D analog calcipotriol interferes with the
      S100-mediated positive feedback loop by suppressing the increased production of
      psoriasin and koebnerisin in psoriatic skin and their Th17-mediated regulation in
      epidermal keratinocytes. Thus, targeting the S100-amplification loop could be a
      beneficial anti-inflammatory approach in psoriasis and other inflammatory skin
      diseases.

PMID- 22402440
TI  - Osteopontin in systemic sclerosis and its role in dermal fibrosis.
AB  - Osteopontin (OPN) is a matricellular protein with proinflammatory and profibrotic
      properties. Previous reports demonstrate a role for OPN in wound healing and
      pulmonary fibrosis. Here, we determined whether OPN levels are increased in a
      large cohort of patients with systemic sclerosis (SSc) and whether OPN
      contributes to the development of dermal fibrosis. The plasma OPN levels were
      increased in SSc patients, including patients with limited and diffuse disease,
      compared with healthy controls. Immunohistology demonstrated OPN on fibroblast
      like and inflammatory cells in SSc skin and lesional skin from mice in the
      bleomycin (bleo)-induced dermal fibrosis model. OPN-deficient (OPN(-/-)) mice
      developed less dermal fibrosis compared with wild-type (WT) mice in the bleo
      induced dermal fibrosis model. Additional in vivo studies have demonstrated that
      lesional skin from OPN(-/-)mice had fewer Mac-3-positive cells, fewer
      myofibroblasts, decreased transforming growth factor (TGF)-beta and genes in the
      TGF-beta pathway, and decreased numbers of cells expressing phosphorylated SMAD2
      (pSMAD) and extracellular signal-regulated kinase. In vitro, OPN(-/-) dermal
      fibroblasts had decreased migratory capacity but similar phosphorylation of SMAD2
      by TGF-beta. Finally, TGF-beta production by OPN-deficient macrophages was
      reduced compared with WT. These data demonstrate an important role for OPN in the
      development of dermal fibrosis and suggest that it may be a new therapeutic
      target in SSc.

PMID- 22402442
TI  - A UVR-induced G2-phase checkpoint response to ssDNA gaps produced by replication
      fork bypass of unrepaired lesions is defective in melanoma.
AB  - UVR is a major environmental risk factor for the development of melanoma. Here we
      describe a coupled DNA-damage tolerance (DDT) mechanism and G2-phase cell cycle
      checkpoint induced in response to suberythemal doses of UVR that is commonly
      defective in melanomas. This coupled response is triggered by a small number of
      UVR-induced DNA lesions incurred during G1 phase that are not repaired by
      nucleotide excision repair (NER). These lesions are detected during S phase, but
      rather than stalling replication, they trigger the DDT-dependent formation of
      single-stranded DNA (ssDNA) gaps. The ssDNA attracts replication protein A (RPA),
      which initiates ATR-Chk1 (ataxia telangiectasia and Rad3-related/checkpoint
      kinase 1) G2-phase checkpoint signaling, and colocalizes with components of the
      RAD18 and RAD51 postreplication repair pathways. We demonstrate that depletion of
      RAD18 delays both the resolution of RPA foci and exit from the G2-phase arrest,
      indicating the involvement of RAD18-dependent postreplication repair in ssDNA gap
      repair during G2 phase. Moreover, the presence of RAD51 and BRCA1 suggests that
      an error-free mechanism may also contribute to repair. Loss of the UVR-induced G2
      phase checkpoint results in increased UVR signature mutations after exposure to
      suberythemal UVR. We propose that defects in the UVR-induced G2-phase checkpoint
      and repair mechanism are likely to contribute to melanoma development.

PMID- 22402443
TI  - Combined use of laser capture microdissection and cDNA microarray analysis
      identifies locally expressed disease-related genes in focal regions of psoriasis
      vulgaris skin lesions.
AB  - Psoriasis vulgaris is a complex disease characterized by alterations in growth
      and differentiation of epidermal keratinocytes, as well as a marked increase in
      leukocyte populations. Lesions are known to contain alterations in messenger RNAs
      encoding more than 1,000 products, but only a very small number of these
      transcripts has been localized to specific cell types or skin regions. In this
      study, we used laser capture microdissection (LCM) and gene array analysis to
      study the gene expression of cells in lesional epidermis (EPI) and dermis,
      compared with the corresponding non-lesional regions. Using this approach, we
      detected >1,800 differentially expressed gene products in the EPI or dermis of
      psoriasis lesions. These results established sets of genes that are
      differentially expressed between epidermal and dermal compartments, as well as
      between non-lesional and lesional psoriasis skin. One of our findings involved
      the local production of CCL19, a lymphoid-organizing chemokine, and its receptor
      CCR7 in psoriatic dermal aggregates, along with the presence of gene products
      LAMP3/DC-LAMP and CD83, which typify mature dendritic cells (DCs). Gene
      expression patterns obtained with LCM and microarray analysis along with T-cell
      and DC detection by immune staining suggest a possible mechanism for lymphoid
      organization via CCL19/CCR7 in diseased skin.

PMID- 22402444
TI  - Langerhans cells from human cutaneous squamous cell carcinoma induce strong type
      1 immunity.
AB  - Langerhans cells (LCs) are dendritic cells (DCs) localized to the epidermis. They
      should be the first antigen-presenting cells to encounter squamous cell carcinoma
      (SCC). The aim of this study was to investigate the ability of LCs isolated from
      human SCC to induce T-cell proliferation and polarization. We investigated the
      ability of LCs from SCC and peritumoral skin to induce T-cell proliferation and
      polarization. We also studied the effect of SCC supernatant on the ability of LCs
      from normal skin, in vitro-generated LCs, and DCs to activate and polarize T
      cells. LCs from SCC were stronger inducers of allogeneic CD4(+) and CD8(+) T-cell
      proliferation and IFN-gamma production than LCs from peritumoral skin. We found
      that tumor supernatants (TSNs) were rich in immunosuppressive cytokines; despite
      this, allogeneic CD4(+) and CD8(+) T-cell proliferation and IFN-gamma induction
      by LCs were augmented by TSN. Moreover, TSN facilitated IFN-gamma induction by in
      vitro-generated LCs, but suppressed the ability of in vitro-generated DCs to
      expand allogeneic CD4(+) and CD8(+) T cells. We have demonstrated that LCs from
      SCC can induce type 1 immunity. TSN induces IFN-gamma induction by in vitro
      generated LCs. This contrasts greatly with prior studies showing that DCs from
      SCC cannot stimulate T cells. These data indicate that LCs may be superior to DCs
      for SCC immunotherapy and may provide a new rationale for harnessing LCs for the
      treatment of cancer patients.

PMID- 22402445
TI  - Generic and personalized RNAi-based therapeutics for a dominant-negative
      epidermal fragility disorder.
AB  - Epidermolytic palmoplantar keratoderma (EPPK) is one of >30 autosomal-dominant
      human keratinizing disorders that could benefit from RNA interference (RNAi)
      based therapy. EPPK is caused by mutations in the keratin 9 (KRT9) gene, which is
      exclusively expressed in thick palm and sole skin where there is considerable
      keratin redundancy. This, along with the fact that EPPK is predominantly caused
      by a few hotspot mutations, makes it an ideal proof-of-principle model skin
      disease to develop gene-specific, as well as mutation-specific, short interfering
      RNA (siRNA) therapies. We have developed a broad preclinical RNAi-based
      therapeutic package for EPPK containing generic KRT9 siRNAs and allele-specific
      siRNAs for four prevalent mutations. Inhibitors were systematically identified in
      vitro using a luciferase reporter gene assay and validated using an innovative
      dual-Flag/Strep-TagII quantitative immunoblot assay. siKRT9-1 and siKRT9-3 were
      the most potent generic K9 inhibitors, eliciting >85% simultaneous knockdown of
      wild-type and mutant K9 protein synthesis at picomolar concentrations. The allele
      specific inhibitors displayed similar potencies and, importantly, exhibited
      strong specificities for their target dominant-negative alleles with little or no
      effect on wild-type K9. The most promising allele-specific siRNA, siR163Q-13, was
      tested in a mouse model and was confirmed to preferentially inhibit mutant allele
      expression in vivo.

PMID- 22402446
TI  - Beyond cancer genomics: after the end of the beginning.

PMID- 22402447
TI  - Cancer epigenomics: beyond genomics.
AB  - For many years cancer research has focused on genetic defects, but during the
      last decade epigenetic deregulation has been increasingly recognized as a
      hallmark of cancer. The advent of genome-scale analysis techniques, including the
      recently developed next-generation sequencing, has enabled an invaluable advance
      in the molecular mechanisms underlying tumor initiation, progression, and
      expansion. In this review we describe recent advances in the field of cancer
      epigenomics concerning DNA methylation, histone modifications, and miRNAs. In the
      near future, this information will be used to generate novel biomarkers of
      relevance to diagnosis, prognosis, and chemotherapeutic response.

PMID- 22402449
TI  - Determination of seven nitrobenzene compounds in mainstream cigarette smoke with
      heart-cutting two-dimensional gas chromatography.
AB  - A heart-cutting two-dimensional gas chromatography (GC) method was developed for
      the determination of nitrobenzene compounds (NBCs) in mainstream cigarette smoke.
      For the method, the particulate matter of cigarette smoke was extracted with
      cyclohexane, purified with a silica solid-phase extraction (SPE) cartridge and
      analyzed by heart-cutting two-dimensional GC equipped with two electron capture
      detectors. The heart-cutting two-dimensional GC was achieved by a single-column
      GC oven equipped with a microfluidic pressure balanced device (Deans switch). Two
      dimensional GC was compared to single-dimensional GC and found to be clearly
      better for the separation of seven NBCs from a complex smoke matrix. The limits
      of detection ranged from 1.28 to 9.83 ng/mL, spiked recoveries were between 88.3
      and 106.8% and relative standard deviation ranged from 2.79 to 12.78%. The NBCs
      yields of six kinds of Chinese and international cigarettes brands, which were
      all smoked according to two smoking protocols (International Organization for
      Standardization and Health Canada Intense smoking regimens), were determined and
      compared.

PMID- 22402448
TI  - Chromosomal translocations and palindromic AT-rich repeats.
AB  - Repetitive DNA sequences constitute 30% of the human genome, and are often sites
      of genomic rearrangement. Recently, it has been found that several constitutional
      translocations, especially those that involve chromosome 22, take place utilizing
      palindromic sequences on 22q11 and on the partner chromosome. Analysis of
      translocation junction fragments shows that the breakpoints of such palindrome
      mediated translocations are localized at the center of palindromic AT-rich
      repeats (PATRRs). The presence of PATRRs at the breakpoints indicates a
      palindrome-mediated mechanism involved in the generation of these constitutional
      translocations. Identification of these PATRR-mediated translocations suggests a
      universal pathway for gross chromosomal rearrangement in the human genome. De
      novo occurrences of PATRR-mediated translocations can be detected by PCR in
      normal sperm samples but not somatic cells. Polymorphisms of various PATRRs
      influence their propensity for adopting a secondary structure, which in turn
      affects de novo translocation frequency. We propose that the PATRRs form an
      unstable secondary structure, which leads to double-strand breaks at the center
      of the PATRR. The double-strand breaks appear to be followed by a non-homologous
      end-joining repair pathway, ultimately leading to the translocations. This review
      considers recent findings concerning the mechanism of meiosis-specific, PATRR
      mediated translocations.

PMID- 22402450
TI  - Aortic annulus sizing: echocardiographic versus computed tomography derived
      measurements in comparison with direct surgical sizing.
AB  - OBJECTIVES: The precise sizing of the aortic annulus is crucial in order to
      select the most appropriate valve size for transcatheter aortic valve
      implantation (TAVI). Owing to the closed heart situation in TAVI, sizing has to
      be performed based on preoperative imaging when compared with direct sizing
      during conventional procedures. The aim of the study was to evaluate valve sizing
      performed either by CT-scan or by echocardiography by comparing these imaging
      based measurements with direct intraoperative sizing. METHODS: Prior to the
      standard conventional aortic valve replacement, 26 patients underwent cardiac CT
      scan and echocardiographic examination. Maximal annular diameter was measured by
      echocardiography at end-diastole and end-systole, including the leaflet
      calcifications. The CT-scan maximal, minimal and mean diameters were measured as
      well as the 'effective' diameter (CT(eff)). CT(eff) represents the diameter of a
      circle with the exact same area as the measured area of the annular circumference
      reconstructed from the CT-data set. Direct intraoperative diameters were measured
      after decalcification using metric sizers. RESULTS: CT(eff) and end-systolic
      echocardiographic diameters showed best agreement with intraoperative direct
      sizing (intraop) in the Bland-Altman analysis [mean difference for
      transoesophageal echocardiography (TEE) vs intraop 0.5 mm (limits of agreement 
      2.5-3.5); mean difference for transthoracic echocardiography (TTE) vs intraop
      0.38 mm (limits of agreement -3.28-4.03) and CT(eff) vs intraop -0.56 (limits of
      agreement -3.16-2.05)]. In patients with an oval-shaped annulus, CT(eff)
      demonstrated the best agreement with intraop [mean difference -0.32 (limits of
      agreement -2.29 to 1.66)]. CONCLUSIONS: Both the 'effective' CT diameter and end
      systolic TEE values are the most reliable approaches for preoperative aortic
      annulus sizing. In patients with a pronounced oval-shaped annulus, the
      'effective' CT diameter seems to be the method of choice. Therefore, aortic
      annulus measurement using 'effective' CT diameters should be included into
      current recommendations for TAVI sizing.

PMID- 22402451
TI  - National trends in lung cancer surgery.
AB  - OBJECTIVES: Trends in lung cancer surgery may reveal potential for improvement
      and are important for planning by care providers. METHODS: Using data from the
      Cancer Registry of Norway, we analysed the outcomes of lung cancer surgery during
      the periods of 1994-95, 2000-01 and 2006-07. The Cox regression model was carried
      out to identify the period effect on survival. RESULTS: A total of 2201 patients
      were operated on. Surgery was centralized from 24 hospitals in the first two
      periods to 13 hospitals in the last. The resection rates varied from 6 to 31%
      across the counties. From the first to the last period, the national resection
      rate increased from 16 to 19% (P(trend) = 0.001), and the 1-year survival rate
      increased from 73 to 82%. The proportion of resected patients in pathological
      stage I-II decreased from 87 to 83% (P(trend) = 0.048), the proportion of
      pneumonectomies from 27 to 15% (P(trend)<0.001), and the rate of mortality within
      30 days of the surgery from 4.8 to 3.0% (P(trend) = 0.072). In the first two
      periods, 31% of these early deaths were caused by complications directly related
      to the surgical technique, whereas, in the latter period, no deaths were directly
      related. The only unfavourable trend was the waiting time between the final
      diagnostic procedure and surgery, which increased from 29 to 40 days throughout
      the three periods (P < 0.001). Survival (excluding those who died within 30 days)
      was significantly improved in the last period (risk ratio (RR): 0.72 (P <
      0.001)). CONCLUSIONS: Despite an increased surgical waiting time, important
      aspects of lung cancer surgery, including resection rates, have improved in
      recent years.

PMID- 22402452
TI  - Pulmonary artery hypertension in heart transplant recipients: how much is too
      much?
AB  - OBJECTIVES: Unresponsive pulmonary hypertension (PH) may contraindicate heart
      transplant since it implies poor early outcomes. The present study reports the
      effectiveness of oral perioperative sildenafil in allowing heart transplant
      candidacy and surgery in a selected group of patients initially deemed ineligible
      because of PH. METHODS: Between May 2005 and December 2009, 31 consecutive
      patients (5 females, 9 with a history of idiopatic cardiomyopathy and 16 with a
      history of coronary artery disease, 10 with previous sternotomies, 71.42 +/-
      27.69 ml/min/m(2) mean preoperative epidermal growth factor receptor) were
      qualified for oral sildenafil because of unresponsive PH at baseline right heart
      catheterization (RHC). After a 12-week trial, RHC disclosed PH reversibility
      (mean pulmonary vascular resistance index: 9.57 +/- 4.07 WU, mean transpulmonary
      gradient 14.47 +/- 5.66 mmHg and mean systolic pulmonary artery pressure: 68.96
      +/- 15.15 mmHg), allowing listing despite a higher risk for early post-transplant
      RV failure. Transplant protocol included donor/recipient size matching >= 0.8 and
      inhaled nitric oxide in the early postoperative period followed by reinstitution
      of oral sildenafil. RESULTS: All patients underwent heart transplantation. Mean
      overall graft ischaemic time was 179 +/- 47 min; mean donor recipient weight
      ratio was 1.04 +/- 0.17. Right ventricular failure developed in three patients
      (9.6%) and hospital mortality was 3.2%. Protocol RHC disclosed pulmonary
      haemodynamic profile normalization within the third postoperative month allowing
      weaning from sildenafil in the 30 hospital survivors. One-year RHC confirmed PH
      reversal (n = 29 patients, all who survived up to 1 year). CONCLUSIONS: This
      pilot prospective uncontrolled trial suggests that oral sildenafil is effective
      in allowing candidacy, safe transplantation and postoperative pulmonary profile
      normalization in potential recipients initially disqualified because of PH.

PMID- 22402453
TI  - Surgical outcomes for patients with pulmonary atresia/major aortopulmonary
      collaterals and Alagille syndrome.
AB  - OBJECTIVES: Pulmonary atresia with major aortopulmonary collateral arteries
      (PA/MAPCAs) is a complex congenital heart defect that has undergone significant
      advances in treatment over the past 15 years. A small subset of patients with
      PA/MAPCAs have associated Alagille syndrome, which can have an adverse impact on
      many other organ systems. The purpose of this study was to review our
      institutional outcomes for the surgical patients with PA/MAPCAs and Alagille
      syndrome. METHODS: This was a retrospective review of patients with PA/MAPCA's
      and Alagille who underwent surgical reconstruction from November 2001 to August
      2011. Fifteen patients were identified in our data base. Thirteen had pulmonary
      atresia with ventricular septal defect (PA/VSD) and two had pulmonary atresia
      with intact ventricular septum (PA-IVS). RESULTS: There has been no early or late
      mortality in this cohort of 15 patients with PA/MAPCA' and Alagille syndrome. The
      patients have undergone a total of 38 cardiac surgical procedures. Ten of the 13
      patients with PA/VSD have achieved complete repair, including unifocalization, a
      right ventricle to pulmonary artery conduit and closure of all intra-cardiac
      shunts. The three unrepaired patients with PA/VSD remain potential candidates for
      eventual complete repair, while the two patients with PA-IVS remain viable
      candidates for a single ventricle pathway. The patients in this series have also
      undergone 12 major non-cardiac procedures. CONCLUSIONS: The data demonstrate that
      surgical reconstruction of PA/MAPCAs can be successfully achieved in patients
      with Alagille syndrome. The longer-term prognosis remains guarded on the basis of
      the multi-organ system involvement of Alagille syndrome.

PMID- 22402454
TI  - Mid-term results of bidirectional cavopulmonary anastomosis and hemi-Mustard
      procedure in anatomical correction of congenitally corrected transposition of the
      great arteries.
AB  - OBJECTIVES: The Senning or Mustard procedure combined with the arterial switch
      operation (ASO) (+/- VSD and no left ventricular (LV) outflow tract obstruction)
      or the Rastelli operation (VSD and LV outflow tract obstruction) has become the
      preferred strategy over conventional repair as it is thought to prevent long-term
      dysfunction of the right ventricle (RV). More recently, hemi-Mustard rerouting of
      blood from the inferior vena cava to the RV in combination with bidirectional
      cavopulmonary anastomosis (BCPA) has been adopted by some centres for potential
      benefits over the classic atrial switch procedure. The aim of this study was to
      analyse our experience with hemi-Mustard and BCPA as part of an anatomical repair
      of congenitally corrected transposition of the great arteries (CCTGA) in selected
      patients. METHODS: Between 2004 and 2011, eight patients underwent hemi
      Mustard/BCPA with the Rastelli operation (n = 6) or ASO (n = 2). The median age
      was 2.9 (range: 1.2-9.1) years. Positional anomalies were present in 75% of the
      patients. Both patients with ASO had dysplastic and insufficient tricuspid
      valves. In the Rastelli group, four patients had previously received shunts
      followed by BCPA in one patient. In the ASO group, both patients underwent
      pulmonary artery banding initially. RESULTS: There was one in-hospital death and
      no late mortality. Two patients received a pacemaker. One patient from the
      Rastelli group required conduit change 6 years later. At the mean follow-up of
      4.5 years, six and one patients are in NYHA classes I and II, respectively; six
      patients showed good biventricular function, while one had LV dysfunction.
      Systemic venous obstruction and sinus node dysfunction were not observed, and
      BCPA was functioning well in all patients. CONCLUSIONS: Hemi-Mustard/BCPA is
      useful in anatomical repair of CCTGA in selected patients. When compared with the
      classic atrial switch operation, it is technically easier which makes it
      especially helpful in atrio-apical discordance; it unloads an RV with limited
      size or function, and avoids complications related to the upper limb of the
      classic atrial switch procedure. Mid-term results of this approach are
      favourable. Further follow-up is needed to prove long-term benefits.

PMID- 22402455
TI  - Diaphragm pacing after bilateral implantation of intradiaphragmatic phrenic
      stimulation electrodes through a transmediastinal endoscopic minimally invasive
      approach: pilot animal data.
AB  - OBJECTIVES: Phrenic nerve stimulation for diaphragm pacing allows patients with
      central respiratory paralysis to be weaned from mechanical ventilation. Two
      procedures are available, either intrathoracic (bilateral thoracotomy) or
      intradiaphragmatic (four ports laparoscopy). The present experimental work
      assesses the feasibility, safety and efficacy of a trans-mediastinal implantation
      of intradiaphragmatic phenic nerve stimulation electrodes using a flexible
      gastroscope through a cervical incision. METHODS: We operated on nine ewes. After
      selective bronchial intubation, we dissected the latero-tracheal space and opened
      both mediastinal pleura. We then introduced a flexible gastroscope into the
      pleural cavities, in a sequential manner. The phrenic nerves were located and
      followed up to the diaphragm dome. Electrodes loaded within a long, pliable
      needle were introduced through the adjacent intercostal space and implanted in
      each hemidiaphragm, at a 'tendinous' location (as close as possible to the entry
      of the nerve in the central tendon), and at a more lateral 'muscular' location.
      Postoperatively, the animals were ventilated using bilateral phrenic nerve
      stimulation. After euthanasia, abdominal verification of the electrodes position
      was performed through a laparotomy. RESULTS: The mediastinal and pleural parts of
      the procedure were uneventful. The insertion of electrodes was associated with
      transdiaphragmatic puncture and small abdominal haematomas in the first two
      animals studied. After a slight modification of the insertion technique, this was
      not observed anymore. Phrenic nerve stimulation produced efficient ventilation,
      with tidal volumes significantly higher when delivered at the tendinous site than
      at the muscular site. CONCLUSIONS: The trans-mediastinal implantation of
      intradiaphragmatic phrenic nerve stimulation electrodes is feasible, appears
      reasonably safe, and allows efficient ventilation.

PMID- 22402456
TI  - Alternative to pulmonary allograft for reconstruction of right ventricular
      outflow tract in small patients undergoing the Ross procedure.
AB  - OBJECTIVES: Small pulmonary allografts are difficult to obtain, thus we now use a
      tailor-made right ventricle to pulmonary artery (RV-PA) conduit for the Ross
      procedure, consisting of a fresh non-treated autologous pericardial (AP) patch
      for the posterior wall and expanded polytetrafluoroethylene (ePTFE) monocusp
      patch for the anterior wall. Long-term durability and RV function were assessed.
      METHODS: Between 1997 and 2011, tailor-made conduits were used for right
      ventricular outflow tract (RVOT) reconstruction in 38 consecutive Ross
      procedures. Patients were divided into two groups by type of material used for
      reconstruction of the RVOT anterior wall: Group A (n = 11), pedicled AP patch
      with ePTFE monocusp valve; Group B (n = 27), ePTFE patch with the ePTFE monocusp
      valve. The posterior wall was reconstructed with an AP patch in both. We examined
      survival and freedom from re-intervention, haemodynamic indices by cardiac
      catheterization, efficacy of the RVOT by ultrasound cardiography (UCG) and
      exercise capacity at 3 years after the operation. The mean follow-up period was
      6.0 +/- 0.5 years. RESULTS: No patients required re-intervention for neo-aortic
      valve. Overall survival and freedom from re-intervention for RVOT reconstruction
      at 10 years were 100 and 100%, respectively, in Group A, and 92.6 and 89.4%,
      respectively, in Group B. No patients showed an RVOT pressure gradient greater
      than 25 mmHg by cardiac catheterization at 1 year after the operation. All showed
      less than 2.5 m/s of RVOT flow estimated by Doppler UCG at 6 years. RV function
      in both groups was preserved at normal in spite of a higher incidence of free
      RVOT insufficiency in Group A (P = 0.018). Exercise capacity was also preserved
      at normal in both groups. CONCLUSIONS: In paediatric patients undergoing the Ross
      procedure, a tailor-made conduit might be helpful to avoid growth-related RVOT
      obstruction. The incidence of free RVOT insufficiency was lower than with an
      anterior ePTFE patch, thus our method may be a better option to preserve RV
      function for a longer period.

PMID- 22402457
TI  - Reaction of a heterotopic P,SAs ligand with group 10 metal(II) complexes: As-S
      bond cleavage and the formation of two unusual trinuclear structural isomers for
      Pd and Pt.
AB  - The synthesis of the heterotopic P,SAs ligand, 1-Ph(2)AsSC(6)H(4)-2-PPh(2) (1)
      and its reaction with [PdCl(2)(cod)], [PtI(2)(cod)] (cod = 1,5-cyclooctadiene)
      and NiCl(2).6H(2)O is reported. Cleavage of the As-S bond of 1 and coordination
      of the resulting phosphanylthiolato ligand (SC(6)H(4)-2-PPh(2))(-) (SC(6)H(4)-2
      PPh(2) = P,S) was observed with formation of [M(P,S)(2)] (M = Ni, Pd, Pt). In the
      case of Pd and Pt, not only the mononuclear complexes [M(P,S)(2)] formed, but
      also the trimers of [MX(P,S)] ([MX{(MU-S-SC(6)H(4)-2-PPh(2))-kappa(2)S,P}](3) [M
      = Pd, X = Cl (2) and M = Pt, X = I (4)]). Formation of 2 and 4 was preceded by
      the trinuclear isomeric intermediates [(cis-M{(MU-S-SC(6)H(4)-2-PPh(2))
      kappa(2)S,P}(2))-MX(2)-MX{(MU-S-SC(6)H(4)-2-PPh(2))-kappa(2)S,P}] [M = Pd, X = Cl
      (3) and M = Pt, X = I (5)]. The crystal structures of 1-5 and a possible reaction
      mechanism that leads to 2 and 4 are presented.

PMID- 22402458
TI  - Legacy and current-use flame retardants in house dust from Vancouver, Canada.
AB  - Fifteen polybrominated diphenyl ethers (PBDEs) and eighteen non-PBDEs were
      measured in 116 dust samples collected from homes in Vancouver, Canada during
      2007-2008 as part of the Chemicals Health and Pregnancy (CHirP) study. The
      highest concentrations of PBDEs in house dust were observed for BDE 209, with a
      median concentration of 1350 ng/g. This is about two times greater than the
      median concentration of the PentaBDE (represented by the most abundant compounds
      in this formulation, SigmaBDE 47, 99 and 100). In the case of non-PBDE FRs, a
      detection frequency between 81% and 100% was observed for nine analytes
      including: HBCD, BTBPE, BEHTBP, EHTBB, HBB, PBTO, PBBe, ATE and DP. The high
      detection of new FRs in indoor environments reflects their ubiquitous presence in
      indoor environment due to regulation of the PBDEs. Exposure to FRs are estimated
      based on these data for adults and toddlers.

PMID- 22402459
TI  - Letter from the editor.

PMID- 22402460
TI  - Update on thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy, which
      is classically associated with signs and symptoms of fever, thrombocytopenia,
      neurologic deficits, hemolytic anemia, and renal failure. It is caused by a
      deficiency of A Disintegrin-like And Metalloprotease with a ThromboSpondin type1
      motif 13 (ADAMTS13), which may be an inherited disorder, but more commonly is an
      acquired disease due to autoantibodies directed against ADAMTS13. Low ADAMTS13
      levels result in increased ultra-large von Willebrand factor multimers, which
      induce platelet adhesion and thrombosis. Plasma exchange therapy is the standard
      of care, and has greatly reduced morbidity and mortality. A recent TTP case is
      reviewed, and treatments for recurrent or refractory TTP are summarized. A
      scoring system using clinical and laboratory parameters to evaluate which
      suspected TTP patients will benefit from plasma exchange therapy is also
      discussed.

PMID- 22402461
TI  - Nilotinib risk evaluation and mitigation strategy.

PMID- 22402462
TI  - Tumor self-seeding in breast cancer.

PMID- 22402463
TI  - Mixed-phenotype acute leukemia: disease features and outcome.

PMID- 22402464
TI  - Sickle cell disease in children.

PMID- 22402466
TI  - Paraneoplastic myopathy.

PMID- 22402465
TI  - Paraneoplastic necrotizing myopathy presenting as severe muscle weakness in a
      patient with small-cell lung cancer: successful response to chemoradiation
      therapy.

PMID- 22402467
TI  - A 21-year-old woman with blastic NK cell leukemia/lymphoma who achieved durable
      remission with HyperCVAD and unrelated umbilical cord blood transplant.

PMID- 22402468
TI  - Treatment of blastic plasmacytoid dendritic cell neoplasms with cord blood
      transplants.

PMID- 22402469
TI  - Real time culture and analysis of embryo metabolism using a microfluidic device
      with deformation based actuation.
AB  - We report a computerized microfluidic real time embryo culture and assay device
      that can perform automated periodic analyses of embryo metabolism. This automated
      program uses a modified "gated injection" scheme (sample injection, reagent
      mixing, enzyme reaction of 15 min incubation, and sample detection) to
      sequentially measure fluorescence from sample, reference, and background (without
      any analyte) every hour. Measurements assessed with reference solutions
      demonstrated the stability of these microfluidic measurements over a 24 h period.
      Furthermore, this system was able to measure time dependent nutrient consumption
      by single or multiple (10) live mouse blastocyst-stage embryos with pmol h(-1)
      sensitivity. Mechanical deformation-based microfluidic actuation created by
      computerized movement of Braille pins enables automated fluid pumping and valving
      sequences without unwanted gravity-driven backflow or exposure to electrical
      fields as would be required in electrokinetic schemes. The convenient, non
      invasive, and automated nature of these assays open the way for the development
      of integrated microfluidic platforms for practical single embryo culture and real
      time biochemical analysis to assess embryo viability and select embryos with the
      greatest implantation potential, thus improving success in clinical assisted
      reproductive technology laboratories.

PMID- 22402470
TI  - Cloning and constitutive expression of His-tagged xylanase GH 11 from Penicillium
      occitanis Pol6 in Pichia pastoris X33: purification and characterization.
AB  - High-level constitutive expression of xylanase GH11 from Penicillium occitanis
      Pol6 termed PoXyn2 was achieved using the methylotrophic yeast Pichia pastoris.
      The PoXyn2 cDNA encoding for a mature xylanase of 320 amino acids was subcloned
      into the pGAPZalphaA vector, to construct recombinant xylanse with six histidine
      residues at the N-terminal and further integrated into the genome of P. pastoris
      X-33 under the control of the glyceraldehyde 3-phosphate dehydrogenase (GAP)
      constitutive promoter. Activity assay and SDS-PAGE demonstrate that the His
      tagged xylanase was extracellularly expressed in P. pastoris and purified to
      homogeneity by a simple, one-step purification protocol using immobilized metal
      affinity chromatography (Ni-NTA resin). The purified PoXyn2 showed a single band
      on SDS-PAGE with an apparent molecular weight of 30 kDa. The xylanase activity
      was optimal at pH 3.0 and 50 degrees C. The specific activity measured for Oat
      Spelt Xylan was 8549.85 U mg(-1). The apparent The K(M) and V(max) values were
      8.33+/-0.7 mg ml(-1)and 58.82+/-0.9 MUmol min(-1) ml(-1), respectively, as
      measured on Oat Spelt Xylan. This is the first report demonstrating the
      possibility of mass production of P. occitanis xylanase using P. pastoris.

PMID- 22402471
TI  - Flutamide increases aldosterone levels in gonadectomized male but not female
      Wistar rats.
AB  - BACKGROUND: Sex-specific differences in blood pressure (BP) suggest an important
      modulating role of testosterone in the kidney. However, little is known about the
      interaction between androgens and the mineralocorticoid aldosterone. Our
      objective was to determine the effects of testosterone in gonadectomized male and
      female rats on a low-salt diet, and to determine the effect of androgen receptor
      (AR) blockade by flutamide on BP and on aldosterone levels. METHODS: Normotensive
      male and female Wistar rats were gonadectomized and put on a low-salt diet. They
      were treated for 16 days with testosterone or placebo. In addition, the animals
      received the AR antagonist flutamide or placebo, respectively. BP was measured by
      tail-cuff method, 24-h urine samples were collected in metabolic cages and blood
      was collected for hormonal measurements. RESULTS: Testosterone increased BP in
      males and females, and this effect could be blocked by flutamide. Flutamide
      treatment itself significantly increased aldosterone levels in male but not in
      female rats. These elevated aldosterone levels could be lowered by testosterone
      treatment during AR blockade. Accordingly to aldosterone levels, flutamide
      increased in males the serum sodium/potassium to urinary sodium/potassium ratio,
      an in vivo indicator of renal aldosterone action. CONCLUSIONS: Testosterone
      regulates BP in male and female gonadectomized rats via the AR. Flutamide by
      itself exerts influence over aldosterone in the absence of gonadal steroid
      replacement suggesting AR involvement in renal sodium handling. These flutamide
      effects were sex-specific and not seen in female rats.

PMID- 22402472
TI  - Watermelon extract supplementation reduces ankle blood pressure and carotid
      augmentation index in obese adults with prehypertension or hypertension.
AB  - BACKGROUND: Ankle-brachial index (ABI) and ankle blood pressure (BP) are
      associated with increased carotid wave reflection (augmentation index, AIx). Oral
      L-citrulline and L-arginine from synthetic or watermelon sources have reduced
      brachial BP, aortic BP, and aortic AIx. A directly measured carotid AIx (cAIx)
      rather than aortic AIx has been proposed as a better measurement of central AIx.
      We evaluated the effects of watermelon extract on ankle BP and cAIx in
      individuals with normal ABI and prehypertension or stage 1 hypertension. METHODS:
      Ankle and brachial systolic BP (SBP), diastolic BP (DBP), mean arterial pressure
      (MAP), cAIx, ABI, and heart rate (HR) were evaluated in the supine position in 14
      adults (11 women/3 men, age 58 +/- 1 years) with prehypertension or stage 1
      hypertension (153 +/- 4 mm Hg). Subjects were randomly assigned to 6 weeks of
      watermelon extract supplementation (L-citrulline/L-arginine, 6 g daily) or
      placebo followed by a 2-week washout period and then crossover. RESULTS: Ankle
      and brachial SBP (-11.5 +/- 3.8 and -15.1 +/- 2.8 mm Hg), DBP (-7.8 +/- 2.3 and 
      7.6 +/- 1.8 mm Hg), and MAP (-9.8 +/- 2.6 and -7.3 +/- 1.8 mm Hg), and cAIx (-8.8
      +/- 2.6 %) decreased significantly (P < 0.05) after watermelon supplementation
      compared to placebo. Watermelon supplementation had no significant effect (P >
      0.05) on ABI and HR. CONCLUSIONS: This study shows that watermelon extract
      supplementation reduces ankle BP, brachial BP, and carotid wave reflection in
      obese middle-aged adults with prehypertension or stage 1 hypertension and normal
      ABI, which may reflect improved arterial function.

PMID- 22402473
TI  - Novel PLA modification of organic microcontainers based on ring opening
      polymerization: synthesis, characterization, biocompatibility and drug
      loading/release properties.
AB  - In the current study, poly lactic acid (PLA) modified hollow crosslinked
      poly(hydroxyethyl methacrylate) (PHEMA) microspheres have been prepared, in order
      to obtain a stimulus-responsive, biocompatible carrier with sustained drug
      release properties. The synthetical process consisted of the preparation of
      poly(methacrylic acid)@poly(hydroxyethyl methacrylate-co-N,N'-methylene
      bis(acrylamide)) microspheres by a two stage distillation-precipitation
      polymerization technique using 2,2'-azobisisobutyronitrile as initiator.
      Following core removal, a PLA coating of the microspheres was formed, after ring
      opening polymerization of DL-lactide, attributing the initiator's role to the
      active hydroxyl groups of PHEMA. The anticancer drug daunorubicin (DNR) was
      selected for the study of loading and release behavior of the coated
      microspheres. The loading capacity of the PLA modified microspheres was found to
      be four times higher than that of the parent ones (16% compared to 4%). This
      coated microspherical carrier exhibited a moderate pH responsive drug release
      behavior due to the pH dependent water uptake of PHEMA, and PLA hydrolysis. The
      in vitro cytotoxicity of both the parent and the DNR-loaded or empty modified
      hollow microspheres has been also examined on MCF-7 breast cancer cells. The
      results showed that although the empty microspheres were moderately cytotoxic,
      the DNR-loaded microspheres had more potent anti-tumor effect than the free drug.
      Therefore, the prepared coated microspheres are interesting drug delivery
      systems.

PMID- 22402474
TI  - Optimization of matrix tablets controlled drug release using Elman dynamic neural
      networks and decision trees.
AB  - The main objective of the study was to develop artificial intelligence methods
      for optimization of drug release from matrix tablets regardless of the matrix
      type. Static and dynamic artificial neural networks of the same topology were
      developed to model dissolution profiles of different matrix tablets types
      (hydrophilic/lipid) using formulation composition, compression force used for
      tableting and tablets porosity and tensile strength as input data. Potential
      application of decision trees in discovering knowledge from experimental data was
      also investigated. Polyethylene oxide polymer and glyceryl palmitostearate were
      used as matrix forming materials for hydrophilic and lipid matrix tablets,
      respectively whereas selected model drugs were diclofenac sodium and caffeine.
      Matrix tablets were prepared by direct compression method and tested for in vitro
      dissolution profiles. Optimization of static and dynamic neural networks used for
      modeling of drug release was performed using Monte Carlo simulations or genetic
      algorithms optimizer. Decision trees were constructed following discretization of
      data. Calculated difference (f(1)) and similarity (f(2)) factors for predicted
      and experimentally obtained dissolution profiles of test matrix tablets
      formulations indicate that Elman dynamic neural networks as well as decision
      trees are capable of accurate predictions of both hydrophilic and lipid matrix
      tablets dissolution profiles. Elman neural networks were compared to most
      frequently used static network, Multi-layered perceptron, and superiority of
      Elman networks have been demonstrated. Developed methods allow simple, yet very
      precise way of drug release predictions for both hydrophilic and lipid matrix
      tablets having controlled drug release.

PMID- 22402475
TI  - A comparative study of roll compaction of free-flowing and cohesive
      pharmaceutical powders.
AB  - Roll compaction is widely adopted as a dry granulation method in the
      pharmaceutical industry. The roll compaction behaviour of feed powders is
      primarily governed by two parameters: the maximum pressure and the nip angle.
      Although the maximum pressure can be measured directly using pressure sensors
      fitted in the rolls, it is not a trivial task to determine the nip angle, which
      is a measure of the size of the compaction zone and hence the degree of
      compression. Thus a robust approach based upon the calculation of the pressure
      gradient, which can be obtained directly from experiments using an instrumented
      roll compactor, was developed. It has been shown that the resulting nip angles
      are comparable to those obtained using the methods reported in literature.
      Nevertheless, the proposed approach has distinctive advantages including (1) it
      is based on the intrinsic features of slip and no-slip interactions between the
      powder and roll surface and (2) it is not necessary to carry out wall friction
      measurements that involve plates that may not be representative of the roll
      compactor in terms of the surface topography and surface energy. The method was
      evaluated by investigating the effect of roll speed for two pharmaceutical
      excipients with distinctive material properties: microcrystalline cellulose (MCC)
      and di-calcium phosphate dihydrate (DCPD). It was found that the maximum pressure
      and nip angle for DCPD, which is a cohesive powder, decrease sharply with
      increasing roll speed whereas they are essentially independent of roll speed for
      MCC, which is an easy flowing powder. The roll compaction behaviour of MCC-DCPD
      mixtures with various compositions was also investigated in order to evaluate the
      effect of flowability. It was found that the nip angle and maximum pressure
      generally increased with improved flowability of the feed powders.

PMID- 22402476
TI  - Carboxymethyl starch: Chitosan monolithic matrices containing diamine oxidase and
      catalase for intestinal delivery.
AB  - The capacity of carboxymethyl starch (CMS):Chitosan monolithic tablets to protect
      diamine oxidase and/or catalase therapeutic enzymes against simulated gastric
      fluid (SGF) and to control their delivery in simulated intestinal fluid (SIF) was
      investigated. Enzyme formulations loaded with grass pea seedlings diamine oxidase
      (PSDAO) vegetal extract, catalase, or PSDAO associated to catalase, were obtained
      by direct compression. The CMS:Chitosan (1:1) matrix afforded a good gastric
      protection to PSDAO and to catalase, when each enzyme was formulated separately.
      Variable amounts of DAO were delivered in the SIF containing pancreatin, with
      maximal release reached at about 8h, a time convenient for tablets to attain the
      colon. Up to 50% of the initial enzymatic activity of catalase formulated with
      CMS:Chitosan was found after 8 h in SIF. For the CMS:Chitosan tablets of bi
      enzymatic formulations containing PSDAO:Catalase, the releases of DAO and of
      catalase were synchronized. The hydrogen peroxide (product of DAO activity) was
      decomposed by the catalase liberated in the same SIF environment. The proposed
      formulations could allow novel therapeutic approaches for the treatment of
      inflammatory bowel diseases, intestinal cancers or pseudo-allergic reactions.

PMID- 22402477
TI  - Assembly of one novel polyoxometalate-based inorganic-organic compound from
      copper-Schiff base building block: synthesis, crystal structure and spectral
      properties.
AB  - A novel copper(II) inorganic-organic hybrid compound
      [CuL(DMF)(CH(3)OH)](2)(PMo(V)Mo(VI)(11)O(40)).2DMF (L=phenyl 2-pyridyl ketone
      azine) 1 has been synthesized and characterized by IR, UV, elemental analysis and
      X-ray crystallography. Cu(II) atom has a distorted square pyramidal environment
      interconnecting with N(3)O(2) donor set. In solid-state there are three types of
      C-H...pi interactions between adjacent [CuL(DMF)(CH(3)OH)](2+), which generate a
      two-dimensional (2D) layer. Adjacent 2D layers form porous channels in which
      polyoxoanions as templates are filled. Simultaneously, the oxygen atoms of
      polyoxoanion as electron acceptors feather multiple intermolecular hydrogen
      bonds, through which giving rise to a 3D supramolecular network. The luminescent
      properties of the compound 1 were investigated in the solid state and in aqueous
      solution at room temperature, respectively.

PMID- 22402478
TI  - Effect of amino acid additives on the growth and physical properties of potassium
      acid phthalate (KAP) crystals.
AB  - Single crystals of potassium acid phthalate (KAP) have been grown from aqueous
      solution by slow evaporation technique by adding l-alanine (LA), glycine (Gly)
      and l-tyrosine (LT) as additives. Powder X-ray diffraction studies confirmed the
      phase formation and amino acids doping into KAP crystals. The optical absorption
      studies reveal that the LA doped crystals possess less absorption of visible ray
      than the pristine, Gly and LT doped KAP crystals. Optical transmission is found
      to be low in LT doped KAP than in all the other crystals. TG-DTA studies show the
      decomposition temperatures to be 255  degrees C, 232  degrees C, 258  degrees C
      and 264  degrees C for pure, LA, Gly and LT doped KAP crystals respectively. SHG
      efficiency of LA doped KAP crystal was found to be 1.1 times (31 mV for KDP and
      34 mV for LA doped KAP) that of potassium dihydrogen phosphate (KDP) crystal.
      This is much higher when compared to that of undoped KAP crystal (12mV). The
      grown crystals were also subjected to FTIR, microhardness and dielectric studies.

PMID- 22402479
TI  - In situ opening/closing of OmpG from E. coli and the splitting of beta-sheet
      signals in ATR-FTIR spectroscopy.
AB  - The pH dependent opening and closure of Escherichia coli OmpG is driven by the
      formation and breaking of hydrogen bridges in beta-strands S11-S13. We have
      investigated the in situ secondary structural changes of OmpG with ATR-FTIR
      difference spectroscopy in order to detect the signals associated with the newly
      established interactions. Curve-fitting of OmpG in two pH conditions revealed the
      splitting and shifting of beta-sheet signals upon opening of the channel. Besides
      secondary structure changes, there are also amino acid side chain signals that
      play active role in opening/closing of the channel. An interaction among
      positively charged arginines and negatively charged aspartic and glutamic acid
      residues is suggested upon closure of the channel while this interaction is
      abolished when the channel opens at higher pH.

PMID- 22402480
TI  - Quantum chemical studies on structure of 2-amino-5-nitropyrimidine.
AB  - FTIR and FT Raman spectra of 2-amino-5-nitropyrimidine (2A5NP) are recorded in
      the region 4000-400 cm(-1) and 3500-0 cm(-1), respectively. Molecular structure
      and vibrational frequencies of 2A5NP have been investigated by density functional
      theory (DFT) calculations using Becke's three parameter exchange functional
      combined with Lee-Yang-Parr correlation (B3LYP) and Hartree fock (HF) method
      employing 6-311++G(d,p) basis set. Calculations have been performed giving
      energies, optimized structure, harmonic vibrational frequencies, IR intensities
      and Raman activities. Raman and IR spectra of 2A5NP were recorded and complete
      assignment of the observed vibrational bands of 2A5NP have been proposed. The
      predicted first hyperpolarizability suggests that the title compound is an
      attractive object for future studies of non-linear optical properties. The
      calculated HOMO-LUMO energies shows that charge transfer occur within the
      molecule and their related molecular properties were also discussed. The
      theoretical FT-IR and FT-Raman spectra for the title compound have also been
      constructed.

PMID- 22402481
TI  - Vibrational study, first hyperpolarizability and HOMO-LUMO analyses on the
      structure of 2-hydroxy-6-nitro toluene.
AB  - Vibrational spectral measurements, namely, FT-infrared (4000-400 cm(-1)) and FT
      Raman (3500-50 cm(-1)) spectra have been made for 2-hydroxy-6-nitrotoluene (HNT)
      and assigned to different normal modes of the molecule. Quantum chemical
      calculations of energies, geometrical structure, harmonic vibrational frequencies
      intensities and vibrational wavenumbers of HNT were carried out by ab initio HF
      and density functional theory (DFT/B3LYP) method with 6-311++G(d,p) basis set.
      The differences between the observed and scaled wave number values of most of the
      fundamentals are very small. The values of the total dipole moment (MU) and first
      hyperpolarizability (beta) of the investigated molecule were computed by using ab
      initio HF and density functional theory (DFT/B3LYP) methods with 6-311++G(d,p)
      basis set quantum mechanical calculations. The calculated results also show that
      the HNT molecule might have microscopic nonlinear optical (NLO) behavior with non
      zero values. A detailed interpretation of the infrared and Raman spectra of HNT
      is also reported based on total energy distribution (TED). The calculated HOMO
      and LUMO energies show that charge transfer occurs within the molecule. The
      results of the calculations were applied to simulated infrared and Raman spectra
      of the title compound which showed excellent agreement with the observed spectra.

PMID- 22402482
TI  - The use of an early ACTH test to identify hypoadrenalism-related hypotension in
      low birth weight infants.
AB  - OBJECTIVE: To investigate if in preterm newborns, an early adrenocorticotropin
      hormone (ACTH) test can identify possible transient adrenal insufficiency (TAI),
      using significant hypotension as a clinical marker. STUDY DESIGN: We studied 40
      premature newborns born 24 to 29 weeks gestational age (GA) before 8 h of life.
      Serum cortisol levels were obtained before and 40 min after administration of 1.0
      mcg kg(-1) cosyntropin. Inotropes were used to treat hypotension based on
      clinical assessment following no response to fluid boluses. Functional
      echocardiogram was used to support the clinical diagnosis of hypotension. The
      accuracy of the ACTH test was evaluated using receiver operating characteristic
      (ROC) curve. RESULT: Study patients had mean GA of 26.6 weeks and birth weight of
      876 g. In all, 30% required inotropes. The area under the ROC curve for the ACTH
      test was 87%. Using a cutoff of an increase in cortisol below 12% from baseline
      had 75% sensitivity and 93% specificity for detecting hypotension. This cutoff
      was associated with bronchopulmonary dysplasia (8/12 vs 7/28, 95% CI: 0.1 to
      0.72), but not with other morbidities or death. CONCLUSION: An early ACTH test
      using the above cutoff has high specificity for detecting hypotension, and thus,
      can serve as a marker for potential TAI in preterm newborns. Future studies
      should focus on identifying those newborns for which steroid supplementation
      would be most beneficial.

PMID- 22402483
TI  - Racial disparity in maternal and fetal-cord bisphenol A concentrations.
AB  - OBJECTIVE: To determine if racial disparities exist in maternal and fetal cord
      serum concentrations of bisphenol A (BPA). STUDY DESIGN: A nested cross-sectional
      study was performed from a cohort of 600 term nulliparas. In 27 patients (8
      Caucasian, 8 African-American and 11 Hispanic), term pre-labor maternal serum and
      corresponding fetal-cord serum were analyzed for BPA. result: African-Americans
      had the highest maternal serum concentrations, 10-fold higher than Caucasians
      (30.13 vs 3.14 ng ml(-1); P=0.038). Hispanics had intermediate concentrations
      with a trend towards higher concentrations compared with Caucasians (24.46 vs
      3.14 ng ml(-1); P=0.051). Overall concentrations were 10-fold higher in maternal
      samples than fetal samples (14.1 vs 1.3 ng ml(-1); P=0.001). Hispanics had higher
      fetal concentrations than non-Hispanics (2.05 vs 0.35 ng ml(-1); P=0.025).
      CONCLUSION: We found significant racial/ethnic differences in maternal/fetal BPA
      concentrations. Further study is needed to determine if these differences reflect
      disparities in exposure, metabolism or placental transfer.

PMID- 22402484
TI  - Utilization of available prenatal screening and diagnosis: effects of the
      California screen program.
AB  - OBJECTIVE: In 2009, the California Genetic Disease Branch introduced an
      aneuploidy screening program allowing Medi-Cal (state insured) patients access to
      state-sponsored first-trimester screening. The objective of this study was to
      assess the effect of greater access to prenatal screening on available resources
      at a single center. STUDY DESIGN: Data of prenatal screening and diagnostic
      procedures performed 4 months before the introduction of the program were
      compared with those of 12 months following the introduction. RESULT: Between
      December 2008 and March 2010, 7689 women underwent first trimester screening,
      1286 underwent amniocentesis and 398 underwent chorionic villus sampling. When a
      comparison was made between the 4 months before and the 12 months after the
      program's introduction, a greater number of nuchal translucency (NT) examinations
      was seen to have been performed (384 per month vs 513 per month, P=0.001).
      Prenatal diagnostic procedures did not increase, but a greater proportion was
      performed for positive screen results. CONCLUSION: Introduction of the California
      screening program was associated with increased NT procedures and fewer invasive
      procedures for advanced maternal age.

PMID- 22402485
TI  - Genetic polymorphisms influence recovery from traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a major public health concern in both civilian
      and military populations. Recently, genetics studies have begun to identify
      individual differences in polymorphisms that could affect recovery and outcome of
      cognitive and social processes following TBI. This review considers the potential
      for polymorphisms to influence six specific cognitive and social functions, which
      represent the most prominent domains of impairment following TBI: working memory,
      executive function, decision making, inhibition and impulsivity, aggression, and
      social and emotional function. Examining the influence of polymorphisms on TBI
      outcome has the potential to contribute to an understanding of variations in TBI
      outcome, aid in the triaging and treatment of TBI patients, and ultimately lead
      to targeted interventions based on genetic profiles.

PMID- 22402486
TI  - Referral source and outcomes of physical therapy care in patients with low back
      pain.
AB  - STUDY DESIGN: Retrospective longitudinal cohort. OBJECTIVES: To describe the
      clinical characteristics of patients with low back pain according to physician
      referral source, and to identify associations between referral source and
      discharge functional status, as well as number of physical therapy visits.
      BACKGROUND: Little is known about associations between physician referral source
      and outcomes of physical therapy care for patients with low back pain. Exploring
      these associations can contribute to better understanding of physician-physical
      therapist relationships and may lead to improved referral patterns. METHODS: Data
      from a proprietary clinical database were examined retrospectively. Physician
      referral source was classified as primary care, specialist, or occupational
      medicine. Outcomes were overall health status at discharge and number of physical
      therapy visits. Descriptive statistics and bivariate associations between
      referral source and each outcome were assessed by calculating differences and 95%
      confidence intervals (CIs) in means and proportions. To account for potential
      confounding, multilevel linear regression was used to adjust for baseline
      clinical covariates, effects related to clustering of patients treated by
      individual clinicians, and clinicians working within individual clinics. RESULTS:
      Bivariate and multilevel analyses revealed significant associations between
      referral source and discharge overall health status, as well as number of visits.
      After multilevel adjustment for covariate and clustering effects, primary care
      and occupational medicine referrals were associated, on average, with point
      increases of 1.6 (95% CI: 0.7, 2.6) and 4.8 (95% CI: 2.7, 6.9) in discharge
      overall health status scores, respectively, compared to specialist referral.
      Similarly, primary care and occupational medicine referrals were associated, on
      average, with 0.44 (95% CI: 0.27, 0.61) and 0.83 (95% CI: 0.44, 1.22) fewer
      visits, respectively, compared to specialist referral. CONCLUSION: After
      accounting for clinical covariates and clustering, patients with low back pain
      who were referred by occupational medicine and primary care physicians tended to
      have better functional outcomes and required fewer physical therapy visits per
      episode of care. LEVEL OF EVIDENCE: Prognosis, level 2c.

PMID- 22402487
TI  - Proteins and DNA elements essential for the CRISPR adaptation process in
      Escherichia coli.
AB  - The clustered regularly interspaced short palindromic repeats and their
      associated proteins (CRISPR/Cas) constitute a recently identified prokaryotic
      defense mechanism against invading nucleic acids. Activity of the CRISPR/Cas
      system comprises of three steps: (i) insertion of alien DNA sequences into the
      CRISPR array to prevent future attacks, in a process called 'adaptation', (ii)
      expression of the relevant proteins, as well as expression and processing of the
      array, followed by (iii) RNA-mediated interference with the alien nucleic acid.
      Here we describe a robust assay in Escherichia coli to explore the hitherto least
      studied process, adaptation. We identify essential genes and DNA elements in the
      leader sequence and in the array which are essential for the adaptation step. We
      also provide mechanistic insights on the insertion of the repeat-spacer unit by
      showing that the first repeat serves as the template for the newly inserted
      repeat. Taken together, our results elucidate fundamental steps in the adaptation
      process of the CRISPR/Cas system.

PMID- 22402488
TI  - HnRNP L and L-like cooperate in multiple-exon regulation of CD45 alternative
      splicing.
AB  - CD45 encodes a trans-membrane protein-tyrosine phosphatase expressed in diverse
      cells of the immune system. By combinatorial use of three variable exons 4-6,
      isoforms are generated that differ in their extracellular domain, thereby
      modulating phosphatase activity and immune response. Alternative splicing of
      these CD45 exons involves two heterogeneous ribonucleoproteins, hnRNP L and its
      cell-type specific paralog hnRNP L-like (LL). To address the complex
      combinatorial splicing of exons 4-6, we investigated hnRNP L/LL protein
      expression in human B-cells in relation to CD45 splicing patterns, applying RNA
      Seq. In addition, mutational and RNA-binding analyses were carried out in HeLa
      cells. We conclude that hnRNP LL functions as the major CD45 splicing repressor,
      with two CA elements in exon 6 as its primary target. In exon 4, one element is
      targeted by both hnRNP L and LL. In contrast, exon 5 was never repressed on its
      own and only co-regulated with exons 4 and 6. Stable L/LL interaction requires
      CD45 RNA, specifically exons 4 and 6. We propose a novel model of combinatorial
      alternative splicing: HnRNP L and LL cooperate on the CD45 pre-mRNA, bridging
      exons 4 and 6 and looping out exon 5, thereby achieving full repression of the
      three variable exons.

PMID- 22402489
TI  - The sub-cellular localization of Sulfolobus DNA replication.
AB  - Analyses of the DNA replication-associated proteins of hyperthermophilic archaea
      have yielded considerable insight into the structure and biochemical function of
      these evolutionarily conserved factors. However, little is known about the
      regulation and progression of DNA replication in the context of archaeal cells.
      In the current work, we describe the generation of strains of Sulfolobus
      solfataricus and Sulfolobus acidocaldarius that allow the incorporation of
      nucleoside analogues during DNA replication. We employ this technology, in
      conjunction with immunolocalization analyses of replisomes, to investigate the
      sub-cellular localization of nascent DNA and replisomes. Our data reveal a
      peripheral localization of replisomes in the cell. Furthermore, while the two
      replication forks emerging from any one of the three replication origins in the
      Sulfolobus chromosome remain in close proximity, the three origin loci are
      separated.

PMID- 22402490
TI  - Air2p is critical for the assembly and RNA-binding of the TRAMP complex and the
      KOW domain of Mtr4p is crucial for exosome activation.
AB  - Trf4/5p-Air1/2p-Mtr4p polyadenylation complex (TRAMP) is an essential component
      of nuclear RNA surveillance in yeast. It recognizes a variety of nuclear
      transcripts produced by all three RNA polymerases, adds short poly(A) tails to
      aberrant or unstable RNAs and activates the exosome for their degradation.
      Despite the advances in understanding the structural features of the isolated
      complex subunits or their fragments, the details of complex assembly, RNA
      recognition and exosome activation remain poorly understood. Here we provide the
      first understanding of the RNA binding mode of the complex. We show that Air2p is
      an RNA-binding subunit of TRAMP. We identify the zinc knuckles (ZnK) 2, 3 and 4
      as the RNA-binding domains, and reveal the essentiality of ZnK4 for TRAMP4
      polyadenylation activity. Furthermore, we identify Air2p as the key component of
      TRAMP4 assembly providing bridging between Mtr4p and Trf4p. The former is bound
      via the N-terminus of Air2p, while the latter is bound via ZnK5, the linker
      between ZnK4 and 5 and the C-terminus of the protein. Finally, we uncover the RNA
      binding part of the Mtr4p arch, the KOW domain, as the essential component for
      TRAMP-mediated exosome activation.

PMID- 22402491
TI  - Combination of Sleeping Beauty transposition and chemically induced dimerization
      selection for robust production of engineered cells.
AB  - The main methods for producing genetically engineered cells use viral vectors for
      which safety issues and manufacturing costs remain a concern. In addition,
      selection of desired cells typically relies on the use of cytotoxic drugs with
      long culture times. Here, we introduce an efficient non-viral approach combining
      the Sleeping Beauty (SB) Transposon System with selective proliferation of
      engineered cells by chemically induced dimerization (CID) of growth factor
      receptors. Minicircles carrying a SB transposon cassette containing a reporter
      transgene and a gene for the F36VFGFR1 fusion protein were delivered to the
      hematopoietic cell line Ba/F3. Stably-transduced Ba/F3 cell populations with >98%
      purity were obtained within 1 week using this positive selection strategy. Copy
      number analysis by quantitative PCR (qPCR) revealed that CID-selected cells
      contain on average higher copy numbers of transgenes than flow cytometry-selected
      cells, demonstrating selective advantage for cells with multiple transposon
      insertions. A diverse population of cells is present both before and after
      culture in CID media, although site-specific qPCR of transposon junctions show
      that population diversity is significantly reduced after selection due to
      preferential expansion of clones with multiple integration events. This non
      viral, positive selection approach is an attractive alternative for producing
      engineered cells.

PMID- 22402492
TI  - CBX4-mediated SUMO modification regulates BMI1 recruitment at sites of DNA
      damage.
AB  - Polycomb group (PcG) proteins are involved in epigenetic silencing where they
      function as major determinants of cell identity, stem cell pluripotency and the
      epigenetic gene silencing involved in cancer development. Recently numerous PcG
      proteins, including CBX4, have been shown to accumulate at sites of DNA damage.
      However, it remains unclear whether or not CBX4 or its E3 sumo ligase activity is
      directly involved in the DNA damage response (DDR). Here we define a novel role
      for CBX4 as an early DDR protein that mediates SUMO conjugation at sites of DNA
      lesions. DNA damage stimulates sumoylation of BMI1 by CBX4 at lysine 88, which is
      required for the accumulation of BMI1 at DNA damage sites. Moreover, we establish
      that CBX4 recruitment to the sites of laser micro-irradiation-induced DNA damage
      requires PARP activity but does not require H2AX, RNF8, BMI1 nor PI-3-related
      kinases. The importance of CBX4 in the DDR was confirmed by the depletion of
      CBX4, which resulted in decreased cellular resistance to ionizing radiation. Our
      results reveal a direct role for CBX4 in the DDR pathway.

PMID- 22402493
TI  - Label-free, atomic force microscopy-based mapping of DNA intrinsic curvature for
      the nanoscale comparative analysis of bent duplexes.
AB  - We propose a method for the characterization of the local intrinsic curvature of
      adsorbed DNA molecules. It relies on a novel statistical chain descriptor, namely
      the ensemble averaged product of curvatures for two nanosized segments,
      symmetrically placed on the contour of atomic force microscopy imaged chains. We
      demonstrate by theoretical arguments and experimental investigation of
      representative samples that the fine mapping of the average product along the
      molecular backbone generates a characteristic pattern of variation that
      effectively highlights all pairs of DNA tracts with large intrinsic curvature.
      The centrosymmetric character of the chain descriptor enables targetting strands
      with unknown orientation. This overcomes a remarkable limitation of the current
      experimental strategies that estimate curvature maps solely from the trajectories
      of end-labeled molecules or palindromes. As a consequence our approach paves the
      way for a reliable, unbiased, label-free comparative analysis of bent duplexes,
      aimed to detect local conformational changes of physical or biological relevance
      in large sample numbers. Notably, such an assay is virtually inaccessible to the
      automated intrinsic curvature computation algorithms proposed so far. We foresee
      several challenging applications, including the validation of DNA adsorption and
      bending models by experiments and the discrimination of specimens for genetic
      screening purposes.

PMID- 22402494
TI  - HIF2alpha-Sp1 interaction mediates a deacetylation-dependent FVII-gene activation
      under hypoxic conditions in ovarian cancer cells.
AB  - Hypoxia-inducible factors (HIF)-1alpha and HIF2alpha are major transcription
      factors required for adaptive responses to hypoxia. HIFs form a complex with aryl
      hydrocarbon receptor nuclear translocator (ARNT) to bind to the regulatory
      regions of target genes. The acetylation of histones by histone
      acetyltransferases (HATs) is one of the epigenetic marks associated with active
      chromatin. Indeed, HIFs recruit p300 HAT to hypoxia response elements (HREs)
      within gene regulatory regions. Here, we report an unusual HIF-mediated
      transcriptional activation in ovarian clear cell carcinoma (CCC). While
      characterizing coagulation factor VII (FVII) gene induction during hypoxic
      conditions, we observed that the interaction of HIF2alpha with Sp1, but not with
      ARNT, could induce transcription of FVII in a HRE-independent manner.
      Unexpectedly, this gene activation is associated with histone deacetylation. We
      found that a class II HDAC, HDAC4, is recruited with HIF2alpha to the FVII
      promoter as a co-activator, while p300 HAT negatively regulated this process.
      Furthermore, this mechanism can be synergistically enhanced via a deacetylation
      dependent pathway when cells are simultaneously exposed to hypoxic and serum-free
      conditions. These results suggest the presence of a stress-responsive
      transcription mediated by the HIF2alpha/Sp1/HDAC4 network and explain how CCC
      shed their procoagulant activity under hypoxia.

PMID- 22402496
TI  - Pilus biogenesis at the outer membrane of Gram-negative bacterial pathogens.
AB  - Pili belong to a broad class of bacterial surface structures that play a key role
      in infection and pathogenicity. The largest and best characterised pilus
      biogenesis system--the chaperone-usher pathway--is particularly remarkable in its
      ability to synthesise and display highly organised structures at the outer
      membrane without any input from endogenous energy sources. The past few years
      have heralded exciting new developments in our understanding of the structural
      biology and mechanism of pilus assembly, which are discussed in this review. Such
      knowledge will be particularly important in the future, as we approach an era of
      widespread resistance to common antibiotics and require new targets.

PMID- 22402495
TI  - The Caenorhabditis elegans GW182 protein AIN-1 interacts with PAB-1 and subunits
      of the PAN2-PAN3 and CCR4-NOT deadenylase complexes.
AB  - GW182 family proteins are essential for miRNA-mediated gene silencing in animal
      cells. They are recruited to miRNA targets via interactions with Argonaute
      proteins and then promote translational repression and degradation of the miRNA
      targets. The human and Drosophila melanogaster GW182 proteins share a similar
      domain organization and interact with PABPC1 as well as with subunits of the PAN2
      PAN3 and CCR4-NOT deadenylase complexes. The homologous proteins in
      Caenorhabditis elegans, AIN-1 and AIN-2, lack most of the domains present in the
      vertebrate and insect proteins, raising the question as to how AIN-1 and AIN-2
      contribute to silencing. Here, we show that both AIN-1 and AIN-2 interact with
      Argonaute proteins through GW repeats in the middle region of the AIN proteins.
      However, only AIN-1 interacts with C. elegans and D. melanogaster PABPC1, PAN3,
      NOT1 and NOT2, suggesting that AIN-1 and AIN-2 are functionally distinct. Our
      findings reveal a surprising evolutionary plasticity of the GW182 protein
      interaction network and demonstrate that binding to PABPC1 and deadenylase
      complexes has been maintained throughout evolution, highlighting the significance
      of these interactions for silencing.

PMID- 22402497
TI  - Computer simulation studies of self-assembling macromolecules.
AB  - Coarse-grained (CG) molecular models are now widely used to understand the
      structure and functionality of macromolecular self-assembling systems. In the
      last few years, significant efforts have been devoted to construct quantitative
      CG models based on data from molecular dynamics (MD) simulations with more
      detailed all-atom (AA) intermolecular force fields as well as experimental
      thermodynamic data. We review some of the recent progress pertaining to the MD
      simulation of self-assembling macromolecular systems, using as illustrations the
      application of CG models to probe surfactant and lipid self-assembly including
      liposome and dendrimersome formation as well as the interaction of biomembranes
      with nanoparticles.

PMID- 22402498
TI  - Impact of a thoracic nurse-led chest drain clinic on patient satisfaction.
AB  - Nurse-led clinics are an increasingly used resource in managing postoperative
      patients and meeting their clinical needs. Since 2007, St James' University
      Hospital has run a ward-based nurse-led clinic; providing follow-up and
      management of patients after thoracic surgery. We aimed to assess patient
      satisfaction with the clinic's ability to manage their postoperative needs. Data
      were collected prospectively from patients attending the clinic between July and
      August 2010 using structured patient questionnaires. We evaluated 83 patient
      feedback questionnaires. The reasons for clinic attendance were predominantly
      wound assessment and chest drain review. Fifty-four (65%) patients were managed
      without seeing a doctor, of whom only four (7%) believed seeing a doctor would
      have been beneficial. Seventy-three (88%) patients stated their needs were met in
      the clinic and 82 (99%) patients described the overall care they received as
      good, very good or excellent. This survey highlights that patients are satisfied
      with a nurse-led service and will hopefully help encourage the development of
      such services within thoracic surgery.

PMID- 22402499
TI  - Pyopericardium followed by constrictive pericarditis due to Corynebacterium
      diphtheriae.
AB  - Pyopericardium is a rare entity associated with a high mortality. We report a
      case of a 44-year old man presenting with simultaneous constrictive pericarditis
      and pyopericardium due to Corynebacterium diphtheriae. Pericardiectomy and
      epicardiectomy were performed without cardiopulmonary bypass, with an excellent
      result.

PMID- 22402500
TI  - Does Warden's procedure reduce sinus node dysfunction after surgery for partial
      anomalous pulmonary venous connection?
AB  - A best evidence topic in cardiothoracic surgery was written according to a
      structured protocol. The question addressed was 'Does Warden's procedure reduce
      sinus node dysfunction (SND) after surgery for partial anomalous pulmonary venous
      connection?' Altogether 101 papers were found using the reported search; of which
      10 papers provided the best evidence to answer the question. The authors,
      journal, date and country of publication, patient group studied, study type,
      relevant outcomes, length of follow-up and results of these studies were
      tabulated. There was a particular reference to Warden's procedure, avoidance of
      incision across the cavoatrial junction and the postoperative sinus node status.
      There was a direct reference to the adoption of Warden's procedure in nine
      studies while one study emphasized the careful use of incision across the
      cavoatrial junction as a way of averting postoperative SND. The evidence supports
      the notion that preservation of the sinus node and its blood supply through the
      adoption of Warden's technique results in near-absent SND during long-term follow
      up. The incidence of SND ranged from 0 to 6.5% when Warden's procedure was used,
      increasing to 18.1% when the atrial incision was extended across the cavoatrial
      junction into the superior vena cava and reaching as high as 55% in double-patch
      repair. The study limitations include the lack of randomized controlled trial,
      absence of 24 h Holter monitoring in most of the patients and shorter periods of
      follow-up.

PMID- 22402501
TI  - Is cold or warm blood cardioplegia superior for myocardial protection?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether the use of warm or cold blood
      cardioplegia has superior myocardial protection. More than 192 papers were found
      using the reported search, of which 20 represented the best evidence to answer
      the clinical question. The authors, journal, date, country of publication,
      patient group studied, study type, relevant outcomes and results of these papers
      are tabulated. A good breadth of high-level evidence addressing this clinical
      dilemma is available, including a recent meta-analysis and multiple large
      randomized clinical trials. Yet despite this level of evidence, no clear
      significant clinical benefit has been demonstrated by warm or cold blood
      cardioplegia. This suggests that neither method is significantly superior and
      that both provide similar efficacy of myocardial protection. The meta-analysis,
      including 41 randomized control trials (5879 patients in total), concluded that
      although a lower cardiac enzyme release and improved postoperative cardiac index
      was demonstrated in the warm cardioplegia group, this benefit was not reflected
      in clinical outcomes, which were similar in both groups. This theme of benefit in
      biochemical markers, physiological metrics and non-fatal postoperative events in
      the warm cardioplegia group ran throughout the literature, in particular the
      'Warm Heart investigators' who conducted a randomized trial of 1732 patients,
      demonstrated a reduction in postoperative low output syndrome (6.1 versus 9.3%, P
      = 0.01) in the warm cardioplegia group, but no significant drop in 30-day all
      cause mortality (1.4 versus 2.5%, P = 0.12). However, their later follow-up
      indicates non-fatal postoperative events predict reduced late survival,
      independent of cardioplegia. A minority of studies suggested a benefit of cold
      cardioplegia over warm in particular patient subgroups: One group conducted a
      retrospective study of 520 patients who required prolonged aortic cross-clamp
      times, results demonstrated less myocardial damage and reduced postoperative
      cardiac mortality and morbidity in the cold group. The clinical bottom line is
      that warm and cold cardioplegia result in similar short-term mortality. However,
      large studies have shown that warm cardioplegia reduces adverse post-operative
      events; the significance of which is unclear.

PMID- 22402502
TI  - Transmanubrial approach with video-assisted thoracoscopic surgery for left
      superior sulcus tumour with dense adhesion after replacement of descending
      thoracic aorta.
AB  - There are various surgical approaches to superior sulcus tumours according to the
      location of the tumour. The chief difficulties in the operation are broadening of
      the operative field and adhesiolysis. This study presents the case of surgical
      treatment of superior sulcus tumour following chemoradiation therapy with dense
      pleural adhesion due to a history of graft replacement of the descending thoracic
      aorta. The patient underwent left upper lobectomy via a transmanubrial
      osteomuscular-sparing approach combined with video-assisted thoracoscopic surgery
      (VATS). Transmanubrial approach combined with VATS offered a good overview during
      local tumour dissection.

PMID- 22402503
TI  - Unidirectional valved patch closure of ventricular septal defects with severe
      pulmonary arterial hypertension.
AB  - Delayed presentation of ventricular septal defect (VSD) is common in developing
      countries. Such patients often have severe pulmonary arterial hypertension (PAH),
      which increases post-operative morbidity and mortality. To address these
      problems, we used our technique of unidirectional valved patch (UVP) for closure
      of VSD. Between January 2006 and December 2010, 17 patients (age 2-23 years,
      median 9 years) with a large VSD and severe PAH underwent VSD closure with UVP.
      Pre-operative mean indexed pulmonary vascular resistance (PVRI) was 10.9 +/- 2.2
      Wood units and mean pre-operative systemic saturation was 93.4 +/- 2.6%. Shunt
      was bidirectional in 15 patients and predominantly right to left in two. After
      VSD closure, intra-operative transoesophageal echocardiography revealed a right
      to left shunt across the patch in three patients 2, 7 and 9 years of age who had
      pre-operative PVRI of 9.5, 9.8 and 11.1 Wood units, respectively. There were no
      in-hospital deaths and all patients had uneventful recovery. Mean follow-up was
      30 +/- 14.7 months and all patients are well without cyanosis. Echocardiography
      showed no shunt across the patch and all have systemic saturation >95%. We
      conclude that UVP is a promising technique in patients with large VSD and severe
      PAH.

PMID- 22402504
TI  - Borondipyrromethene-derived Cu2+ sensing chemodosimeter for fast and selective
      detection.
AB  - Here, we report a new Cu(2+)-selective fluorescent turn-on probe BODIPY-EP, in
      which the 2-pyridinecarboxylic acid is connected to a 6-hydroxyindole-based
      BODIPY platform through an ester linkage. The ester bond of BODIPY-EP is
      selectively hydrolyzed by the reaction with Cu(2+) under mild and neutral
      conditions to generate BODIPY-OH, showing strong characteristic fluorescence of
      BODIPY-OH. The favorable features of BODIPY-EP towards Cu(2+) include fast
      response, large fluorescence enhancement and high selectivity. We further
      demonstrated that the membrane-permeable probe reacts with intracellular Cu(2+)
      and exhibits bright fluorescence in living cells.

PMID- 22402505
TI  - Cis-regulation and conserved non-coding elements in amphioxus.
AB  - The origin of the vertebrates was a major event in the evolution of morphological
      diversity and the genetic mechanisms responsible for this diversity, once purely
      theoretical, can now be approached experimentally in the genome era. With a
      prototypical chordate genome, vertebrate-like development and simple morphology,
      amphioxus provides the appropriate model for investigating the origin of the
      vertebrates. Comparative genomics is revealing that both conservation and
      divergence of genes and cis-regulatory elements involved in developmental
      regulatory networks are required to shape different animal body plans. This
      article reviews the cis-regulatory studies performed in amphioxus, the discovery
      of conserved non-coding elements (CNEs) across the metazoans and the examination
      of amphioxus CNEs. Emerging ideas on the evolution of CNEs after large-scale
      genome duplication events and the state of cephalochordate genomics are also
      discussed.

PMID- 22402507
TI  - Regulation and function of mammalian DNA methylation patterns: a genomic
      perspective.
AB  - Mammalian DNA methyltransferases (DNMTs) establish and maintain genomic DNA
      methylation patterns that are required for proper epigenetic regulation of gene
      expression and maintenance of genome stability during normal development.
      Aberrant DNA methylation patterns are implicated in a variety of pathological
      conditions including cancer and neurological disorders. Rapid advances in genomic
      technologies have allowed the generation of high resolution whole-genome views of
      DNA methylation and DNA methyltransferase occupancy in pluripotent stem cells and
      differentiated somatic cells. Furthermore, recent identification of oxidation
      derivatives of cytosine methylation in mammalian DNA raises the possibility that
      DNA methylation patterns are more dynamic than previously anticipated. Here, we
      review the recent progress in our understanding of the genomic function and
      regulatory mechanisms of mammalian DNA methylation.

PMID- 22402509
TI  - Carcinoma of the anal canal: small steps in treatment advances.
AB  - For locally advanced squamous cell carcinoma of the anal canal, efforts to
      discover effective treatments that would protect sphincter preservation led to
      the development of combined chemoradiotherapy, which, when administered
      appropriately, is curative. While the standard of combined modality
      chemoradiotherapy has minimally changed over the past 30 years, various
      chemotherapeutic and biologic agents, as well as novel methods for delivering
      radiation, have enhanced the treatment of anal carcinoma and are continuously
      being explored. This review examines the risk factors associated with anal
      carcinoma, and subsequently discusses the current standard of care from diagnosis
      through surveillance, paying attention to the pivotal trials that have shaped
      modern treatment paradigms.

PMID- 22402506
TI  - The amphioxus genome provides unique insight into the evolution of immunity.
AB  - Immune systems evolve as essential strategies to maintain homeostasis with the
      environment, prevent microbial assault and recycle damaged host tissues. The
      immune system is composed of two components, innate and adaptive immunity. The
      former is common to all animals while the latter consists of a vertebrate
      specific system that relies on somatically derived lymphocytes and is associated
      with near limitless genetic diversity as well as long-term memory. Deuterostome
      invertebrates provide a view of immune repertoires in phyla that immediately
      predate the origins of vertebrates. Genomic studies in amphioxus, a
      cephalochordate, have revealed homologs of genes encoding most innate immune
      receptors found in vertebrates; however, many of the gene families have undergone
      dramatic expansions, greatly increasing the innate immune repertoire. In
      addition, domain-swapping accounts for the innovation of new predicted pathways
      of receptor function. In both amphioxus and Ciona, a urochordate, the VCBPs
      (variable region containing chitin-binding proteins), which consist of
      immunoglobulin V (variable) and chitin binding domains, mediate recognition
      through the V domains. The V domains of VCBPs in amphioxus exhibit high levels of
      allelic complexity that presumably relate to functional specificity. Various
      features of the amphioxus immune repertoire reflect novel selective pressures,
      which likely have resulted in innovative strategies. Functional genomic studies
      underscore the value of amphioxus as a model for studying innate immunity and may
      help reveal how unique relationships between innate immune receptors and both
      pathogens and symbionts factored in the evolution of adaptive immune systems.

PMID- 22402511
TI  - Weibel-Palade bodies.

PMID- 22402512
TI  - Novel targets for triple-negative breast cancer.

PMID- 22402513
TI  - Optimal timing for transplant in multiple myeloma.

PMID- 22402514
TI  - Advances in biomarkers for targeted agents.

PMID- 22402515
TI  - A patient with necrobiotic xanthogranuloma presenting with an anterior
      mediastinal mass, plasma cell dyscrasia, and a lymphoproliferative disorder.

PMID- 22402516
TI  - Necrobiotic xanthogranuloma.

PMID- 22402517
TI  - Relapsed diffuse large B-cell lymphoma--10 years later.

PMID- 22402518
TI  - Late relapses in diffuse large B-cell lymphoma.

PMID- 22402519
TI  - The Health and Social Care Bill: why all English people should be worried.

PMID- 22402520
TI  - The wrong direction?

PMID- 22402521
TI  - Open letter. RE: NHS Health Reform Bill.

PMID- 22402522
TI  - A contrary view.

PMID- 22402523
TI  - Organic toothpaste.

PMID- 22402534
TI  - The entrepreneurial role in primary care dentistry.
AB  - This paper explores the entrepreneurial role of dentists in primary care
      dentistry. It reviews the changing context of dentistry, not least the reforms
      being introduced by the health and social care bill. It suggests that this new
      context will reinforce the need to consider the business side of dental practice,
      in particular, the importance of quality, creativity and innovation, alongside
      the importance of meeting the needs of patients. An entrepreneurial approach will
      be required in order to sustain dental practice in an increasingly competitive
      environment.

PMID- 22402535
TI  - Evidence-based dentistry: analysis of dental anxiety scales for children.
AB  - OBJECTIVES: To review paediatric dental anxiety measures (DAMs) and assess the
      statistical methods used for validation and their clinical implications. METHOD:
      A search of four computerised databases between 1960 and January 2011 associated
      with DAMs, using pre-specified search terms, to assess the method of validation
      including the reliability as intra-observer agreement 'repeatability or
      stability' and inter-observer agreement 'reproducibility' and all types of
      validity. RESULTS: Fourteen paediatric DAMs were predominantly validated in
      schools and not in the clinical setting while five of the DAMs were not validated
      at all. The DAMs that were validated were done so against other paediatric DAMs
      which may not have been validated previously. Reliability was not assessed in
      four of the DAMs. However, all of the validated studies assessed reliability
      which was usually 'good' or 'acceptable'. None of the current DAMs used a formal
      sample size technique. Diversity was seen between the studies ranging from a few
      simple pictograms to lists of questions reported by either the individual or an
      observer. CONCLUSION: To date there is no scale that can be considered as a gold
      standard, and there is a need to further develop an anxiety scale with a
      cognitive component for children and adolescents.

PMID- 22402540
TI  - Summary of: Estimating the need for dental sedation. 4. Using IOSN as a referral
      tool.

PMID- 22402541
TI  - Summary of: Access to primary dental care for cleft lip and palate patients in
      South Wales.

PMID- 22402542
TI  - Evaluation of Tier 5 Medical Training Initiative opportunities in dentistry.
AB  - This paper reviews the first two years of overseas postgraduate dental placements
      in the UK under the Medical Training Initiative (MTI), which is part of Tier 5
      government authorised exchange. Details of the objectives of the programme, the
      trainees appointed, specialty areas studied and length of training are described.
      The methods used for assessing the training are reported. It is concluded that
      the objectives of the MTI have been met in dentistry and that Tier 5 provides a
      valuable opportunity for establishing international links in postgraduate
      clinical dentistry.

PMID- 22402543
TI  - Intravenous lipid emulsion - rescued at LAST.
AB  - The accidental overdose of local anaesthetics may prove fatal. The commonly used
      amide local anaesthetics have varying adverse effects on the myocardium and
      beyond a certain dose all are capable of causing death. Local anaesthetics are
      the most frequently used drugs in dentistry and although uncommon, local
      anaesthetic systemic toxicity (LAST) accounts for a high proportion of
      mortalities in the dental office, with local anaesthetic-induced cardiac arrest
      particularly resistant to standard resuscitation methods. Over the last decade
      there has been convincing evidence of using intravenous lipid emulsions as a
      rescue in local anaesthetic - cardiotoxicity and anaesthetic organisations over
      the globe have developed guidelines on the use of this drug. Despite this,
      however, awareness among practitioners appears to be lacking. All who use local
      anaesthetics in their practice should have an appreciation of patients at high
      risk of toxicity, early symptoms and signs of toxicity, preventative measures
      when using these drugs and the initial management of systemic toxicity with
      intravenous lipid emulsion. In this review we intend to discuss the pharmacology
      and pathophysiology of local anaesthetic toxicity, and the rationale for
      intravenous lipid emulsion therapy.

PMID- 22402544
TI  - Europe's oldest jaw: evidence of oral pathology.
AB  - Atapuerca, in the north of Spain, is the archaeological site where the oldest
      hominid remains within Europe have been found. In 2008 a jaw fragment,
      corresponding to the symphyseal area, was discovered in the area called the
      'Elephant's pit'. Its age has been estimated at 1.2 million years and it is
      considered to be the oldest human fossil found in Europe and is from the lower
      Pleistocene. This work analyses the dental and skeletal damage to the specimen,
      detected in a macroscopic study of possible horizontal and vertical bone loss at
      the level of support of the remaining teeth. The limited presence of dental
      scale, the pattern of destruction and the decreased bone density due to increased
      marrow spaces suggest the presence of possible periodontal disease.

PMID- 22402563
TI  - Access to primary dental care for cleft lip and palate patients in South Wales.
AB  - AIM: To determine the provision of NHS primary dental care for children with
      cleft lip and/or palate in South Wales and the ease of accessing this dental
      care. METHOD: A postal questionnaire was sent to all cleft lip and/or palate
      patients under the age of 18 (n = 750) in South Wales. The questionnaire
      identified patients' medical history, episodes of dental emergency, distance from
      home to dental surgery and ease of accessing primary dental care. To increase the
      response rate a second questionnaire was posted to non-responders. RESULTS: The
      response rate was 49% (368/750). The majority of patients (92%, n = 340) attended
      a dentist. Over 17% (n = 61) had suffered an episode of dental emergency. About
      63% (n = 240) lived within 5 miles of their primary dental care provider, and 13%
      (n = 66) lived more than 10 miles away. Other medical problems were found in over
      30% (n = 111) of the sample. Parents of 39% (n = 107) found it difficult or
      impossible to access a local NHS dentist. CONCLUSION: Many children with cleft
      lip and/or palate find it difficult or impossible to access NHS primary dental
      care. Shortcomings in the services provided to this high risk group have been
      highlighted. Further research is needed at national levels to evaluate the extent
      of the shortcomings and propose methods to overcome them.

PMID- 22402564
TI  - Estimating the need for dental sedation. 4. Using IOSN as a referral tool.
AB  - OBJECTIVE: In this article we report on the use of the IOSN as a referral tool in
      primary care and the need for sedation in the referred patient population (as
      determined by the IOSN score). SETTING: Four centres in the North West of England
      (primary care) accepting referrals for treatment with the aid of sedation
      participated in this study. DESIGN: A service evaluation. SUBJECTS (MATERIALS)
      AND METHODS: The four were provided with IOSN referral forms, operator and
      patient questionnaires. The centres distributed IOSN forms to referrers as a
      means of recommending patients for sedation. All patients receiving treatment
      under sedation (having been referred for treatment through the IOSN form) were
      asked to complete the patient questionnaire. The individual operator who
      undertook the treatment under sedation was asked to complete the operator
      questionnaire. Data were entered into SPSS and the IOSN score noted. Statistical
      analyses of the data utilised descriptives and comparisons between groups using
      the Chi Squared test. RESULTS: Seventy-eight percent of the patients (n = 140) in
      this study were receiving treatment with sedation appropriately according to the
      principals of the IOSN. Patients deemed by the IOSN tool to have a low need for
      sedation were less likely to cancel their appointment if sedation had not been
      given. The majority of patients were female (70%) and the majority of operators
      and patients reported the IOSN forms acceptable for use. CONCLUSIONS: This study
      provides support for using the IOSN as a tool for organising sedation referral.
      The majority of operators and patients reported the IOSN forms acceptable for
      use.

PMID- 22402565
TI  - A patient with tyrosine kinase 2 deficiency without hyper-IgE syndrome.
AB  - We describe a Turkish patient with tyrosine kinase 2 deficiency who suffered from
      disseminated Bacille Calmette-Guerin infection, neurobrucellosis, and cutaneous
      herpes zoster infection. Tyrosine kinase 2 deficiency should be considered in
      patients susceptible to herpes viruses and intramacrophage pathogens even in the
      absence of atopy, high serum IgE, and staphylococcal disease.

PMID- 22402566
TI  - Systematic review of the influence of energy and protein intake on protein
      balance in critically ill children.
AB  - OBJECTIVE: To examine the influence of protein and energy intakes on protein
      balance in children receiving mechanical ventilation in the pediatric intensive
      care unit. STUDY DESIGN: We hypothesized that higher energy and protein intakes
      are correlated with positive protein balance. We performed a systematic
      literature search to identify studies reporting protein balance in children
      requiring mechanical ventilation. Factors contributing to protein balance,
      including protein and energy intake, age, illness severity, study design, and
      feeding routes, were analyzed using a qualitative approach. RESULTS: Nine studies
      met the entry criteria and were included in the final analysis. Positive nitrogen
      balance was reported in 6 of the studies, with a wide range of associated energy
      and protein intakes. Measures of central tendency for daily energy and protein
      intakes were significantly correlated with positive protein balance. A minimum
      intake of 57 kcal/kg/day and 1.5 g protein/kg/day were required to achieve
      positive protein balance. CONCLUSION: We found a correlation between higher
      energy and protein intakes and achievement of positive protein balance in
      children receiving mechanical ventilation in the pediatric intensive care unit.
      However, there is a paucity of interventional studies, and a variety of protocols
      have been used to determine nitrogen balance. Larger clinical trials with uniform
      methodology are needed to further examine the effect of energy and protein intake
      on protein balance, lean body mass, and clinical outcomes in children on
      mechanical ventilation.

PMID- 22402567
TI  - Preventive nephrology: a role for the pediatrician.

PMID- 22402568
TI  - Randomized trial of early bubble continuous positive airway pressure for very low
      birth weight infants.
AB  - OBJECTIVE: To determine whether very low birth weight infants (VLBWIs), initially
      supported with continuous positive airway pressure (CPAP) and then selectively
      treated with the INSURE (intubation, surfactant, and extubation to CPAP;
      CPAP/INSURE) protocol, need less mechanical ventilation than those supported with
      supplemental oxygen, surfactant, and mechanical ventilation if required
      (Oxygen/mechanical ventilation [MV]). STUDY DESIGN: In a multicenter randomized
      controlled trial, spontaneously breathing VLBWIs weighing 800-1500 g were
      allocated to receive either therapy. In the CPAP/INSURE group, if respiratory
      distress syndrome (RDS) did not occur, CPAP was discontinued after 3-6 hours. If
      RDS developed and the fraction of inspired oxygen (FiO(2)) was >0.35, the INSURE
      protocol was indicated. Failure criteria included FiO(2) >0.60, severe apnea or
      respiratory acidosis, and receipt of more than 2 doses of surfactant. In the
      Oxygen/MV group, in the presence of RDS, supplemental oxygen without CPAP was
      given, and if FiO(2) was >0.35, surfactant and mechanical ventilation were
      provided. RESULTS: A total of 256 patients were randomized to either the
      CPAP/INSURE group (n = 131) or the Oxygen/MV group (n = 125). The need for
      mechanical ventilation was lower in the CPAP/INSURE group (29.8% vs 50.4%; P =
      .001), as was the use of surfactant (27.5% vs 46.4%; P = .002). There were no
      differences in death, pneumothorax, bronchopulmonary dysplasia, and other
      complications of prematurity between the 2 groups. CONCLUSION: CPAP and early
      selective INSURE reduced the need for mechanical ventilation and surfactant in
      VLBWIs without increasing morbidity and death. These results may be particularly
      relevant for resource-limited regions.

PMID- 22402569
TI  - Genomic organization, promoter characterization and expression analysis of the
      leukocyte cell-derived chemotaxin-2 gene in Epinephelus akaraa.
AB  - Leucocyte cell-derived chemotaxin 2 (LECT2) was first identified as a chemotactic
      factor and has been subsequently proven to be a multifunctional protein that
      mediates the regulation of liver regeneration, carcinogenesis and Natural killer
      T (NKT) cell homeostasis in mammals. In fish, it has been recently found to be
      critical for the inflammatory response to stimuli. However, the in vivo function
      of LECT2 in fish remains obscure. Base on the full-length cDNA of the Epinephelus
      akaraa LECT2 (EaLECT2) gene we previously isolated, we sought to analyze its
      genomic structure and context. The genomic DNA of the EaLECT2 gene spans 2866bp
      from the transcription start site to the termination codon. As in most LECT2
      genes in other vertebrates, the EaLECT2 genomic DNA contains four exons and three
      introns. An analysis of the promoter region revealed the presence of a TATA box
      and several putative transcription factor-binding sites. And transcriptional
      activity analysis suggested that most basal DNA regulatory elements required for
      EaLECT2 transcriptional activity might be contained within the 581bp region
      upstream of the transcription start codon. A real-time PCR analysis showed that
      the EaLECT2 expression levels were slightly increased in the head kidney, liver,
      gill and brain by bacterial challenge with Vibrio harveyi. Furthermore, the
      transcriptional level of the EaLECT2 gene in the liver was significantly up
      regulated within 1h and reached its peak level at 12h post-stimulation. Higher
      levels of LECT2 expression were also observed in head kidney in challenged
      individuals.The expression pattern demonstrates the role of EaLECT2 in the immune
      response and its functions under other conditions. Additionally, we found that
      the recombinant EaLECT2 could be expressed as a soluble protein using a
      prokaryotic expression system with the expression vector pET32a(+) and the
      soluble protein was further proved to be the recombinant EaLECT2 with the rat
      antiserum against EaLECT2 we obtained. This work provides a unique basis for
      substantial work in future projects.

PMID- 22402570
TI  - Tunnelling control of chemical reactions--the organic chemist's perspective.
AB  - Even though quantum mechanical tunnelling has been appearing recurrently mostly
      in theoretical studies that emphasize its decisive role for many chemical
      reactions, it still appears suspicious to most organic chemists. Recent
      experiments in combination with powerful computational approaches, however, have
      demonstrated that tunnelling must be included to fully understand chemical
      reactivity. Here we provide an overview of the importance of tunnelling in
      organic chemical reactions.

PMID- 22402571
TI  - Roles of pharmacists in expanding access to safe and effective medical abortion
      in developing countries: a review of the literature.
AB  - Unsafe abortion continues to be a major contributor to maternal mortality and
      morbidity around the world. This article examines the role of pharmacists in
      expanding women's access to safe medical abortion in Latin America, Africa, and
      Asia. Available research shows that although pharmacists and pharmacy workers
      often sell abortion medications to women, accurate information about how to use
      the medications safely and effectively is rarely offered. No publication covered
      effective interventions by pharmacists to expand access to medical abortion, but
      lessons can be learned from successful interventions with other reproductive
      health services. To better serve women, increasing awareness and improving
      training for pharmacists and pharmacy workers about unsafe abortion - and
      medications that can safely induce abortion - are needed.

PMID- 22402572
TI  - Traveling interface modulations in the NH3 + O2 reaction on a Rh(110) surface.
AB  - A new type of traveling interface modulation has been observed in the NH(3) +
      O(2) reaction on a Rh(110) surface. A model is set up which reproduces the
      effect, which is attributed to diffusional mixing of two spatially separated
      adsorbates causing an excitability which is strictly localized to the vicinity of
      the interface of the adsorbate domains.

PMID- 22402573
TI  - A comparative study on vibrational, conformational and electronic structure of
      alpha,alpha'-diol-o-xylene, alpha,alpha'-diol-m-xylene and alpha,alpha'-diol-p
      xylene.
AB  - The Fourier transform infrared (FTIR) and FT-Raman spectra of alpha,alpha'-diol-o
      xylene (DOLOX), alpha,alpha'-diol-m-xylene (DOLMX) and alpha,alpha'-diol-p-xylene
      (DOLPX) of the configuration HOCH(2)-C(6)H(4)-CH(2)OH have been recorded in the
      range 4000-400 and 4000-100 cm(-1), respectively. The most stable geometry of the
      compounds was determined by conformational analysis. The complete vibrational
      assignment and analysis of the fundamental modes of the most stable conformer of
      the compounds were carried out using the experimental FTIR and FT-Raman data and
      quantum chemical studies. The observed vibrational frequencies were compared with
      the wavenumbers derived theoretically for the optimised geometry of the compounds
      from the DFT-B3LYP gradient calculations employing the standard 6-31G** and high
      level and 6-311++G** basis sets. The structural parameters and vibrational
      wavenumbers obtained from the DFT method are in good agreement with the
      experimental data. The potential energy distributions of the fundamental modes
      were also calculated by Wilson's FG matrix method. The effect of -CH(2)OH groups
      on the skeletal vibrations have been discussed. The intra molecular n->sigma* and
      pi->pi* interactions were discussed with NBO analysis.

PMID- 22402574
TI  - Adsorption of caffeic acid on titanium dioxide: a spectroscopic study.
AB  - Caffeic acid is an ortho-phenol found in vegetable tissues presenting important
      properties such as carcinogenesis inhibitor, anti-oxidant, anti-viral, anti
      inflammatory and anti-rheumatic actions. It was observed that caffeic acid was
      not degraded in daylight during the adsorption on TiO(2) at pH 4.8. The
      adsorption fit very well to a Brunauer-Emmett-Teller isotherm equation with a
      monolayer coverage of 68.15 mg(CA)g(-1)(TiO2 and saturation coverage of 195.4
      mg(CA)g(-1)(TiO2). A strong adsorption of caffeic acid was verified on TiO(2) for
      the dry solid obtained from the mixture. The Raman and IR spectroscopies revealed
      that the adsorption should occur through the interaction of the diphenol oxygens
      with contribution of CC double bond of the acrylic group, however, the carboxylic
      acid group did not have participation in the adsorption.

PMID- 22402575
TI  - Raman spectroscopy analysis of pigments on 16-17th c. Persian manuscripts.
AB  - The palette of four Persian manuscripts of the 16th and 17th centuries were
      established by Raman microscopy to include lazurite, red lead, vermilion,
      orpiment, a carbon-based black, lead white, malachite, haematite, indigo, carmine
      and pararealgar. The first five pigments were identified on all four manuscripts,
      as previously found for other Islamic manuscripts of this period. The findings
      were compared with information available in treatises on Persian painting
      techniques. Red lead, although identified on all of the manuscripts analysed in
      this study as the main red pigment, is seldom mentioned in the literature. Two
      unusual pigments were also identified: the intermediate phase between realgar and
      pararealgar in the manuscript Timur namah, and carmine in the manuscript Shah
      namah. Although the established palette comprises few pigments, it was found that
      the illuminations were enhanced by the use of pigment mixtures, the components of
      which could be identified by Raman microscopy.

PMID- 22402576
TI  - Ionic comonomer effect of poly(N-isopropylacrylamide) copolymer containing D-pi-A
      type pyran-based fluorescent dye.
AB  - Temperature and pH responsive poly(N-isopropylacrylamide) (poly(NIPAM)) copolymer
      containing D-pi-A type pyran-based fluorescent dye (fluorophore) and basic
      comonomer, N-[3-(dimethylamino)propyl]-methacrylamide (DMAPAM) was prepared by
      free radical polymerization. With increase of pH values, aqueous poly(NIPAM-co
      DMAPAM-co-fluorophore) solution showed decrease of a lower critical solution
      temperature (LCST) and increase of fluorescence intensity, due to a change in the
      ionization state. And also hydrodynamic radius of poly(NIPAM-co-DMAPAM-co
      fluorophore) changed correspondingly to changes of temperature and pH values.

PMID- 22402577
TI  - Spectral characterization of the binding and conformational changes of serum
      albumins upon interaction with an anticancer drug, anastrozole.
AB  - The present study employed different optical spectroscopic techniques viz.,
      fluorescence, FTIR, circular dichroism (CD) and UV-vis absorption spectroscopy to
      investigate the mechanism of interaction of an anticancer drug, anastrozole (AZ)
      with transport proteins viz., bovine serum albumin (BSA) and human serum albumin
      (HSA). The drug, AZ quenched the intrinsic fluorescence of protein and the
      analysis of results revealed the presence of dynamic quenching mechanism. The
      binding characteristics of drug-protein were computed. The thermodynamic
      parameters, enthalpy change (DeltaH degrees ) and entropy change (DeltaS degrees
      ) were calculated to be +92.99 kJ/mol and +159.18 J/mol/K for AZ-BSA and, +99.43
      kJ/mol and +159.19 J/mol/K for AZ-HSA, respectively. These results indicated that
      the hydrophobic forces stabilized the interaction between the drug and protein.
      CD, FTIR, absorption, synchronous and 3D fluorescence results indicated that the
      binding of AZ to protein induced structural perturbation in both serum albumins.
      The distance, r between the drug and protein was calculated based on the theory
      of Forster's resonance energy transfer and found to be 5.9 and 6.24 nm,
      respectively for AZ-BSA and AZ-HSA.

PMID- 22402578
TI  - Spectroscopic investigation on the mechanism of formation of molecular complexes
      of albendazole and trimethoprim with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.
AB  - UV-vis, (1)H NMR, FT-IR, mass and fluorescence spectral techniques were employed
      to investigate the mechanism of interaction of albendazole and trimethoprim with
      2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and to characterize the reaction
      products. The interaction of DDQ with trimethoprim (TMP) and albenadazole (ALB)
      were found to proceed through the formation of donor-acceptor complex, containing
      DDQ radical anion and its conversion to the product. Fluorescence quenching
      studies indicated that the interaction between the donors and the acceptor are
      spontaneous and the interaction of TMP-DDQ (binding constant=2.9*10(5)) is found
      to be stronger than that the ALB-DDQ (binding constant=3*10(3)) system. Also, the
      binding constant increased with an increase in polarity of the medium indicating
      the involvement of radical anion as intermediate.

PMID- 22402579
TI  - Experimental and theoretical study of the inclusion complexes of 3
      carboxycoumarin acid with beta- and 2-hydroxypropyl-beta-cyclodextrins.
AB  - The association process of a host-guest system, cyclodextrins (CyD) - 3
      carboxycoumarin acid (3CCA) was followed by means of UV-vis, circular dichroism
      and steady-state fluorescence spectroscopies in buffer solution at pH=1. The
      experimental data were analyzed in order to get information on the stoichiometry,
      the equilibrium constants and the geometry of the inclusion complexes. In the
      circular dichroism spectra, a positive induced signal was obtained reflecting
      that the guest penetrates the cavity in such a way that the transition moment of
      the electronic band is quasi parallel to the host main axis. The experimental
      data are supported by the DFT and TDDFT (B3LYP/6-31G) calculations performed on
      the isolated ligand and by TDDFT (ZINDO) calculations carried out on the
      supramolecular ligand-cyclodextrin system.

PMID- 22402580
TI  - Synthesis and characterization of some bi, tri and tetravalent transition metal
      complexes of N'-(furan-2-yl-methylene)-2-(p-tolylamino)acetohydrazide HL1 and N'
      (thiophen-2-yl-methylene)-2-(p-tolylamino)acetohydrazide HL2.
AB  - The tetradentate Schiff bases hydrazone ligands HL(1), HL(2) and their metal
      complexes have been prepared and characterized by analytical, spectral (IR, UV
      vis, (1)H NMR and ESR), molar conductivity, magnetic and TGA measurements. The
      results show that all the metal complexes are non-electrolytes, except (2, 10 and
      20) which have ionic nature. The ligands coordinate in keto-neutral form and act
      as bidentate or tridentate for all metal complexes, except complexes (4 and 12).
      The ligands react as monobasic tetradentate and tridentate for complexes (4 and
      12), respectively. Octahedral/tetrahedral Co(II) and Ni(II), octahedral/square
      planar Cu(II), and octahedral Mn(II), Fe(III), Cr(III), Ru(III), Hf(IV) and
      Zr(IV)O geometries were proposed. The ESR spectra of copper complexes (12 and 14)
      indicate d(x2-y2) ground state with covalent bond character. The thermal
      decomposition and the types of crystallized water for some metal complexes were
      studied. The studied metal complexes are very weakly active against the tested
      microorganisms.

PMID- 22402581
TI  - Integration of field effect transistor-based biosensors with a digital
      microfluidic device for a lab-on-a-chip application.
AB  - A new platform for lab-on-a-chip system is suggested that utilizes a biosensor
      array embedded in a digital microfluidic device. With field effect transistor
      (FET)-based biosensors embedded in the middle of droplet-driving electrodes, the
      proposed digital microfluidic device can electrically detect avian influenza
      antibody (anti-AI) in real time by tracing the drain current of the FET-based
      biosensor without a labeling process. Digitized transport of a target droplet
      enclosing anti-AI from an inlet to the embedded sensor is enabled by the
      actuation of electrowetting-on-dielectrics (EWOD). A reduction of the drain
      current is observed when the target droplet is merged with a pre-existing droplet
      on the embedded sensor. This reduction of the drain current is attributed to the
      specific binding of the antigen and the antibody of the AI. The proposed hybrid
      device consisting of the FET-based sensor and an EWOD device, built on a coplanar
      substrate by monolithic integration, is fully compatible with current fabrication
      technology for control and read-out circuitry. Such a completely electrical
      manner of inducing the transport of bio-molecules, the detection of bio
      molecules, the recording of signals, signal processing, and the data transmission
      process does not require a pump, a fluidic channel, or a bulky transducer. Thus,
      the proposed platform can contribute to the construction of an all-in-one chip.

PMID- 22402582
TI  - Endocrine archeology: do insects retain ancestrally inherited counterparts of the
      vertebrate releasing hormones GnRH, GHRH, TRH, and CRF?
AB  - Vertebrate releasing hormones include gonadotropin releasing hormone (GnRH),
      growth hormone releasing hormone (GHRH), corticotropin releasing hormone (CRF),
      and thyrotropin-releasing hormone (TRH). They are synthesized in the hypothalamus
      and stimulate the release of pituitary hormones. Here we review the knowledge on
      hormone releasing systems in the protostomian lineage. We address the question:
      do insects have peptides that may be phylogenetically related to an ancestral
      GnRH, GHRH, TRH, and CRF? Such endocrine archeology has become possible thanks to
      the growing list of fully sequenced genomes as well as to the continuously
      improving bioinformatic tool set. It has recently been shown that the ecdysozoan
      (nematodes and arthropods) adipokinetic hormones (AKHs), the lophotrochozoan
      (annelids and mollusks) GnRHs as well as the protochordate GnRHs are structurally
      related. The adipokinetic hormone precursor-related peptides (APRPs), in locusts
      encoded by the same gene that contains the AKH-coding region, have been forwarded
      as the structural counterpart of GHRH of vertebrates. CRF is relatively well
      conserved in insects, in which it functions as a diuretic hormone. Members of TRH
      receptor family seem to have been conserved in some arthropods, but other
      elements of the thyroid hormone signaling system are not. A challenging idea is
      that in insects the functions of the thyroid hormones were taken over by juvenile
      hormone (JH). Our reconstruction suggests that, perhaps, the ancestral releasing
      hormone precursors played a role in controlling energy metabolism and water
      balance, and that releasing hormone functions as present in extant vertebrates
      were probably secondarily acquired.

PMID- 22402583
TI  - Effects of unloading on knee articular cartilage T1rho and T2 magnetic resonance
      imaging relaxation times: a case series.
AB  - STUDY DESIGN: Case series. BACKGROUND: It has been shown in rodent and canine
      models that cartilage composition is significantly altered in response to long
      term unloading. To date, however, no in vivo human studies have investigated this
      topic. The objective of this case series was to determine the influence of
      unloading and reloading on T1rho and T2 relaxation times of articular cartilage
      in healthy young joints. CASE DESCRIPTION: Ten patients who required 6 to 8 weeks
      of non-weight bearing (NWB) for injuries affecting the distal lower extremity
      participated in the study. Quantitative T1rho and T2 imaging of the ipsilateral
      knee joint was performed at 3 time points: (1) prior to surgery (baseline), (2)
      immediately after a period of NWB (post-NWB), and (3) after 4 weeks of full
      weight bearing (post-FWB). Cartilage regions of interest were segmented and
      overlaid on T1rho and T2 relaxation time maps for quantification. Descriptive
      statistics are provided for all changes. OUTCOMES: Increases of 5% to 10% in
      T1rho times of all femoral and tibial compartments were noted post-NWB. All
      values returned to near-baseline levels post-FWB. Increases in medial tibia T2
      times were noted post-NWB and remained elevated post-FWB. The load-bearing
      regions showed the most significant changes in response to unloading, with
      increases of up to 12%. DISCUSSION: The observation of a transient shift in
      relaxation times confirms that cartilage composition is subject to alterations
      based on loading conditions. These changes appear to be mostly related to
      proteoglycan content and more localized to the load-bearing regions. However,
      following 4 weeks of full weight bearing, relaxation times of nearly all regions
      had returned to baseline levels, demonstrating reversibility in compositional
      fluctuations. LEVEL OF EVIDENCE: Therapy, level 4.

PMID- 22402584
TI  - Reduction of activated macrophages after ischaemia-reperfusion injury diminishes
      oxidative stress and ameliorates renal damage.
AB  - BACKGROUND: Macrophages are major effectors of the local inflammatory response
      syndrome (LIRS) and influence the extent of ischaemia/reperfusion injury, thereby
      impacting organ function. Several subgroups of macrophages exist, representing
      distinct modes of action. The specific role of the subset expressing Fc gamma
      receptor (FcgammaR) 1 in the activated state of macrophages is poorly defined.
      METHODS: We induced a LIRS via 30 min of ischaemia in uninephrectomized rats,
      transgenic for the human FcgammaR1. Six hours after reperfusion, the treatment
      group was injected with a recombinant immunotoxin (IT) H22(scFv)-ETA' targeted
      against human FcgammaR1, which induced apoptosis of target cells. The placebo
      group received normal saline (NS). Contralateral kidneys served as healthy
      controls (Ctr). After 24 h of reperfusion, the animals were analysed. RESULTS:
      Targeted treatment with IT resulted in preserved renal function [NS versus IT
      treatment and baseline (creatinine: 69.2 +/- 2.6, 54.7 +/- 3.4 and 27.3 +/- 1.0
      MUmol/L; P < 0.001)]. The number of all infiltrating monocytes were significantly
      reduced (CD68-positive cells per view field: NS 3.8 +/- 0.4, IT 2.5 +/- 0.2 and
      Ctr 1.2 +/- 0.4; P < 0.05), renal histology improved and there was a reduced
      expression of renal fibronectin (NS 4.0 +/- 0.4, IT 2.3 +/- 0.2 and Ctr 1.1 +/-
      0.1; P < 0.001). Following IT administration, we also observed less expression of
      renal monocyte chemoattractant protein-1-positive cells per view field (NS 19.0
      +/- 1, IT 10.1 +/- 0.8 and Ctr 2.0 +/- 0.3; P < 0.001) as well as reduced
      systemic and local oxidative stress [serum malondialdehyde (MDA): NS 340 +/- 30,
      IT 224 +/- 36 versus baseline 140 +/- 5 nmol/mL; P < 0.01]; renal MDA arbitrary
      units of fluorescence intensity: NS 3.7 +/- 0.2, IT 1.8 +/- 0.3 and Ctr 0.4 +/-
      0.2; P < 0.001. CONCLUSIONS: Reduction of FcgammaR1-up-regulated monocytic cells
      leads to preserved renal function and morphology in a rat model of ischaemia
      triggered LIRS. Our results show that targeting activated macrophages is a
      valuable approach for ameliorating ischaemia-induced tissue injury.

PMID- 22402585
TI  - Comparison of high-resolution computed tomography with conventional injection
      fitting method for fabricating hearing aid shells.

PMID- 22402586
TI  - Effect of Asian sand dust on mucin production in NCI-H292 cells and allergic
      murine model.
AB  - OBJECTIVE: To investigate the effect of Asian sand dust (ASD) on mucin production
      in human respiratory epithelial cells in vitro and in allergic murine nasal
      epithelial cells. STUDY DESIGN: Controlled, in vitro. SETTING: Academic research
      laboratory. MATERIALS AND METHODS: Human NCI-H292 cells were treated with ASD and
      analyzed by immunostaining, reverse transcriptase-polymerase chain reaction for
      MUC5AC mRNA expression, and Periodic Acid Schiff (PAS) staining. Forty female
      BALB/c mice were classified into 4 groups. Two groups were sensitized with
      ovalbumin (OVA), and 1 of these was treated with ASD (ASD+OVA). The 2
      nonsensitized groups were treated with ASD or saline. Then the murine nasal
      mucosal tissues were evaluated by hematoxylin and eosin (H&E) staining, PAS
      staining, and immunostaining for MUC5AC and transforming growth factor (TGF)
      alpha proteins. RESULTS: The numbers of MUC5AC-immunopositive NCI-H292 cells and
      PAS-positive NCI-H292 cells were significantly higher in the ASD-treated cells
      than in the control cells (P = .039 and P = .029, respectively). MUC5AC mRNA
      expression in the cells increased with increasing concentrations of ASD. In the
      murine nasal epithelial tissues, the numbers of eosinophils and PAS-positive
      cells were significantly higher in the ASD+OVA group than in the OVA group (H&E
      staining, P = .037; PAS staining, P = .019). At 2 weeks, the numbers of MUC5AC-
      and TGF-alpha-positive cells in the nasal epithelial tissue were significantly
      higher in the ASD+OVA group than in the OVA group (P = .031 and P = .033,
      respectively). CONCLUSION: ASD can induce mucin production in respiratory
      epithelial cells.

PMID- 22402587
TI  - Antagonic activities of Trypanosoma cruzi metacaspases affect the balance between
      cell proliferation, death and differentiation.
AB  - Metacaspases are distant relatives of animal caspases present in plants, fungi
      and protozoa. At variance with caspases, metacaspases exhibit stringent
      specificity for basic amino-acid residues and are absolutely dependent on
      millimolar concentrations of calcium. In the protozoan parasite Trypanosoma
      cruzi, metacaspases have been suggested to be involved in an apoptosis-like
      phenomenon upon exposure of the parasite to fresh human serum (FHS). Nuclear
      relocalization of metacaspases was observed after FHS treatment and
      overexpression of metacaspase-5 led to enhanced sensitivity to this stimulus.
      Here we report some biochemical properties of T. cruzi metacaspases. Performing
      fluorescent-activated cell sorting (FACS) analysis of epimastigotes inducibly
      overexpressing metacaspase-3, we demonstrate a role for this metacaspase in cell
      cycle progression, protection of epimastigotes from naturally occurring cell
      death and differentiation to infective metacyclic trypomastigotes. We also show
      that regulation of metacaspase-3 activity is important for cell cycle completion
      inside the mammalian host. On the other hand, inducible overexpression of
      metacaspase-5 lacking its C-terminal domain caused an apoptotic-like response.
      These results suggest that the two T. cruzi metacaspases could play an important
      role in the life cycle and bring to light the close relationship between cell
      division, death and differentiation in this ancient unicellular eukaryote.

PMID- 22402588
TI  - STAT3 can serve as a hit in the process of malignant transformation of primary
      cells.
AB  - The transcription factor signal transducer and activator of transcription 3
      (STAT3) acts downstream of many pro-oncogenic signals, including cytokines,
      growth factors and oncogenes, and is accordingly constitutively active in a wide
      variety of tumors that often become addicted to it. Moreover, STAT3 is a key
      player in mediating inflammation-driven tumorigenesis, where its aberrant
      continuous activation is typically triggered by local or systemic production of
      the pro-inflammatory cytokine IL-6. We recently showed that mouse embryonic
      fibroblasts (MEFs) derived from STAT3C k/in mice, which express physiological
      levels of the constitutively active mutant STAT3C, display features of
      transformed cells such as increased proliferation, resistance to apoptosis and
      senescence, and aerobic glycolysis. Here, we show that pre-existing
      constitutively active STAT3 is sufficient to prime primary MEFs for malignant
      transformation upon spontaneous immortalization. Transformation is strictly STAT3
      dependent and correlates with high resistance to apoptosis and enhanced
      expression of anti-apoptotic/pro-survival genes. Additionally, hypoxia inducible
      factor (HIF)-1alpha level is elevated by twofold and contributes to STAT3
      oncogenic activity by supporting high rates of aerobic glycolysis. Thus,
      constitutively active STAT3, an accepted essential factor for tumor
      growth/progression, can also act as a first hit in multistep carcinogenesis; this
      ability to predispose cells to malignant transformation may be particularly
      relevant in the pro-oncogenic niche represented by chronically inflamed tissues.

PMID- 22402590
TI  - Gold-catalyzed efficient synthesis of 2,4-disubstituted furans from aryloxy
      enynes.
AB  - A series of (E)-1-aryloxy-1-en-3-ynes has been prepared by Sonogashira coupling
      of 2-bromo-3-aryloxypropenoates with terminal alkynes using Pd(PPh(3))(4) and CuI
      as the catalysts in Et(3)N. The resulting enynyl-aryl ethers are found to be
      highly applicable to the synthesis of 2,4-disubstituted furans with an ester
      group at C-4 position through an Au/Ag-catalyzed annulation reaction under
      extremely mild reaction conditions.

PMID- 22402589
TI  - Mental and physical health in Rwanda 14 years after the genocide.
AB  - PURPOSE: To examine the socio-demographic determinants of post-traumatic stress
      disorder (PTSD) and its association with major depressive episode and self
      perceived physical and mental health in a large random sample of the Rwandan
      population 14 years after the 1994 genocide. METHODS: Using the Mini
      International Neuropsychiatric Interview and Medical Outcomes Study 36-Item Short
      Form (SF-36) translated in Kinyarwanda, we interviewed 1,000 adult residents from
      the five provinces of Rwanda. Socio-demographic data and specific somatic
      symptoms were also recorded. Data analysis included 962 questionnaires. RESULTS:
      Participants were predominantly female (58.9%), aged between 16 and 34 years
      (53.2%), with a low level of education (79.7% below secondary school). Prevalence
      of PTSD was estimated to be 26.1%. In multivariable analysis, factors associated
      with PTSD were being aged between 25 and 34 years, living in extreme poverty,
      having endured the murder of a close relative in 1994, being widowed or
      remarried, having lost both parents and living in the South Province.
      Participants who fulfilled diagnostic criteria for PTSD were significantly more
      often affected with major depression (68.4 vs. 6.6%, P < 0.001) and substance
      dependence (7.6 vs. 3.5%, P = 0.013) than respondents without PTSD. They scored
      significantly lower on all SF-36 subscales. Somatic symptoms such as hiccups,
      fainting and loss of speech or hearing delineated a specific pattern of post
      traumatic stress syndrome. CONCLUSIONS: PTSD remains a significant public health
      problem in Rwanda 14 years after the genocide. Facilitating access to appropriate
      care for all those who need it should be a national priority.

PMID- 22402591
TI  - The Visible Human Projects in Korea and China with improved images and diverse
      applications.
AB  - PURPOSE: The Visible Human Projects, which were launched in the United States,
      have also been developed in Korea and China during the past decade. This article
      includes the new trials to promote a variety of their applications. METHODS: In a
      Korean laboratory, whole bodies of two cadavers were serially sectioned (Visible
      Korean), while two Chinese institutes have sectioned nine cadavers (Chinese
      Visible Human and Virtual Chinese Human). For acquiring sectioned images and
      stereoscopic models of better quality, appropriate cadavers were chosen;
      equipments and techniques for embedding, sectioning, photography, and computer
      processing were continuously improved in the two countries. To facilitate the
      research, Korean and Chinese scientists have visited each other. RESULTS: The
      sectioned images with thinner intervals (0.2 mm or less) and higher resolution
      were obtained. From the advanced data, the segmented images of comprehensive
      structures were prepared to construct three-dimensional models. Then, cross
      sectional images and models were offered for medical education and clinical
      practice such as electronic anatomy atlas and virtual lumbar puncture.
      CONCLUSION: Every project has its strengths and weaknesses with regard to the
      image data; users in the world can choose the project that best suits their
      needs.

PMID- 22402592
TI  - Evaluation of photodynamic treatment using aluminum phthalocyanine tetrasulfonate
      chloride as a photosensitizer: new approach.
AB  - Photodynamic therapy (PDT) has been the subject of several clinical studies.
      Evidence to date suggests that direct cell death may involve apoptosis. T(24)
      cells (bladder cancer cells, ATCC-Nr. HTB-4) were subjected to PDT with aluminum
      phthalocyanine tetrasulfonate chloride (AlS(4)Pc-Cl) and red laser light at 670
      nm. Morphological changes after PDT were visualized under confocal microscopy.
      Raman microspectroscopy is considered as one of the newly established methods
      used for the detection of cytochrome c as an apoptotic marker. Results showed
      that PDT treated T(24) cells seem to undergo apoptosis after irradiation with 3 J
      cm(-2). Cytochrome c could not be detected from cells incubated with AlS(4)Pc-Cl
      using Raman spectroscopy whereas AlS(4)Pc-Cl seems to interfere with the Raman
      spectrum of cytochrome c.

PMID- 22402593
TI  - A facile in situ microfluidic method for creating multivalent surfaces: toward
      functional glycomics.
AB  - An in situ method of modifying the chemistry and topology of microfluidic
      surfaces in order to mimic the cellular environment is described. The binding of
      functionalised microbeads to microfluidic channels allows the surface-to-volume
      ratio of the system, and thus the number of biomolecules available for reaction,
      to be vastly increased, thereby enhancing the sensitivity of biochemical
      analyses. The sensitivity and specificity of the technique were first
      investigated via the study of carbohydrate-protein interactions. Beads featuring
      hydrazide moieties were adhered to the channel surface, after which carbohydrates
      (galactose and mannose) were bound to the beads in situ and reacted with
      fluorescently labelled proteins. Results showed a six-fold increase in
      fluorescent signal compared to the same process performed on a glass surface
      without the presence of beads, thereby demonstrating the increase in valence
      afforded by the method. In a subsequent study, beads, modified with galactose
      moieties via the in situ functionalisation technique, were used to perform
      studies of colon tumour cells from a cell sample. Here, the carcinoma cells
      exhibited superior adhesion than the normal cells due to an increased expression
      of active galactose receptors, thereby demonstrating the success of the
      biofunctionalisation method for investigating cellular mechanisms.

PMID- 22402594
TI  - Expression, purification and antimicrobial activity of puroindoline A protein and
      its mutants.
AB  - Wheat puroindoline proteins, PINA and PINB, play key roles in determining wheat
      grain hardness as well as in defending the plant against pathogens. PINA has much
      greater membrane-binding property and antimicrobial activity because it contains
      more tryptophan residues in the unique tryptophan-rich domain (TRD). In order to
      obtain proteins with higher antimicrobial activity, mutants of PINA containing
      two or three copies of TRD, designated ABBC and ABBBC, respectively, were
      constructed and expressed in E. coli Rosetta-gami (DE3). Metal affinity
      chromatography was used to purify the soluble affinity-tagged recombinant
      proteins. The secondary structures of the recombinant proteins were predicted by
      the online program Protein Homology/analog Y Recognition Engine v2.0 and
      experimentally assessed using circular dichroism. Minimum inhibition
      concentration tests and fluorescence microscope analyses were employed to
      evaluate the antimicrobial activities of the mutants. The results showed that the
      purified recombinant ABBC was correctly folded and presented significantly higher
      antimicrobial activities against E. coli and S. aureus than wild-type PINA,
      suggesting its potential use as an antimicrobial agent. The results also
      confirmed that TRD is a determinant of the antimicrobial activity of PINA and
      demonstrated that it is feasible to enhance the antimicrobial activity of PINA by
      adding one copy of TRD.

PMID- 22402595
TI  - Strain-independent global effect of hippocampal proteins in mice trained in the
      Morris water maze.
AB  - A series of individual proteins have been linked to performance in the Morris
      water maze (MWM) but no global effects have been reported. It was therefore the
      aim of the study to show which proteins were strain-independent, global factors
      for training in the MWM. Strains C57BL/6J, apodemus sylvaticus and PWD/PhJ were
      used. MWM and gels from trained animals were from a previous own study and
      corresponding yoked groups were generated. Hippocampal proteins were extracted
      and run on two-dimensional gel electrophoresis. Spots with different expressional
      levels between trained and yoked groups were punched and identified by mass
      spectrometry (nano-LC-ESI-MS/MS, ion trap). Two-way ANOVA with two factors
      (strain and training) was carried out and a Bonferroni test was used to compare
      groups. 12 proteins from several pathways and cascades showed different levels in
      trained mice versus corresponding yoked animals in all strains tested. Four out
      of these proteins were verified by immunoblotting: beta-synuclein, profilin 2,
      nucleoside diphosphate kinase A (NME1) and isocitrate dehydrogenase 3. Four
      proteins verified by immunoblotting could be shown to be involved in training in
      the MWM as a global effect, independent of the strain tested.

PMID- 22402596
TI  - Rabbit-antithymocyte globulin combined with cyclosporin A as a first-line
      therapy: improved, effective, and safe for children with acquired severe aplastic
      anemia.
AB  - PURPOSE: Acquired aplastic anemia is an organ-specific auto-immune disease
      characterized by pancytopenia and hypoplastic bone marrow. Immunosuppression with
      anti-thymocyte globulin (ATG) and cyclosporine A (CsA) is an effective and safe
      therapy for patients without undergoing hematopoietic stem cell transplantation.
      The aim of the current study was to investigate the effect of rabbit-ATG (r-ATG)
      combined with CsA as an intensive immunosuppressive therapy (IST) for acquired
      severe aplastic anemia (SAA) in children. METHODS: From January 2003 to November
      2008, 46 children (30 boys and 16 girls), with a median age of 7 years (between 2
      and 15 years) were diagnosed with acquired SAA. They received an IST of r-ATG
      combined with CsA. The average time was 3.4 months (ranging from 1 to 13 months).
      The effective rates 3, 6, 9, and 12 months after treatment were 30.4, 65.2, 78.8,
      and 84.8%, respectively. After 2 years of follow-up, the response rate was 84.8%
      (39/46). No response was found in five cases and relapse was found in two.
      RESULTS: Among the five cases without response, two received unrelated
      hematopoietic stem cell transplantation and are already disease-free and two died
      from infection caused by long-term dependence on infusion. No myelodysplastic
      syndrome or acute myeloid leukemia was found among the patients. CONCLUSIONS: We
      propose that r-ATG combined with CsA as an intensive IST is effective and safe in
      treating acquired SAA in children.

PMID- 22402597
TI  - Fludarabine combined with radiotherapy in patients with locally advanced NSCLC
      lung carcinoma: a phase I study.
AB  - BACKGROUND AND PURPOSE: Fludarabine is an adenine nucleoside analogue that has
      significant activity in hematological malignancies and has shown promising
      activity in combination with radiation in preclinical solid tumor models. We
      designed a phase I trial exploring concurrent fludarabine and radiotherapy in
      patients with advanced non-small cell lung cancer (NSCLC) to determine the
      maximum tolerated dose (MTD) of fludarabine given with concurrent irradiation.
      MATERIALS AND METHODS: Thirteen patients with stage IIIB NSCLC received thoracic
      irradiation of 60 Gy. Fludarabine was administered during the 5th and 6th week of
      radiotherapy. Doses started at 10 mg/m(2) per day and increased by steps of 3
      mg/m(2) per day. RESULTS: At a daily dose of 16 mg/m(2), one out of six patients
      developed a grade 4 leukopenia, and one a grad 3 pneumonitis. Further grade III
      toxicity was not observed. The dose of 13 mg/m(2) was identified as the MTD. All
      patients developed a fludarabine dose-dependent lymphocytopenia. CONCLUSION:
      Fludarabine can be safely administered concurrently with radiation at a daily
      dose of 13 mg/m(2) during the final 2 weeks of radiotherapy. Further prospective
      clinical studies are required to establish the potential role of concurrent
      fludarabine and radiotherapy in the treatment of locally advanced inoperable
      NSCLC.

PMID- 22402598
TI  - Surgical resection for advanced hepatocellular carcinoma according to Barcelona
      Clinic Liver Cancer (BCLC) staging.
AB  - PURPOSE: The BCLC staging classification has been widely endorsed to predict the
      prognosis of patients with HCC. However, its validity as a means of therapeutic
      instructions needs to be challenged. This study aimed to evaluate perioperative
      and long-term outcomes of surgical resection in patients with advanced
      hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer
      (BCLC) staging. METHODS: This study used a prospectively maintained database
      consisting of a consecutive series of 511 Chinese patients with advanced HCC who
      underwent surgical resection in a hepatobiliary surgical center from 2001 to
      2007. Mortality, morbidity, long-term overall survival (OS) and disease-free
      survival (DFS) were evaluated. RESULTS: Hospital mortality was 2.3%, and overall
      morbidity was 31.3%. After a median follow-up period of 27.8 months (range, 0-112
      months), the 1-, 3- and 5-year OS rate was 69.9, 41.2 and 30.5%, and the 1-, 3-
      and 5-year DFS rate was 48.2, 30.3 and 24.0%, respectively. The 1-, 3- and 5-year
      OS and DFS rates were significantly poorer in patients with vascular invasion
      and/or extrahepatic spread than those in patients without (both P < 0.001), and
      also poorer in patients with biliary invasion than those in patients without
      (both P < 0.05). CONCLUSIONS: Surgical resection could be considered in part of
      patients with advanced HCC (BCLC stage C), with low mortality, acceptable
      morbidity and favorable survival benefits. These results imply that BCLC
      recommendations for treatment schedules of advanced HCC need to be re-evaluated.

PMID- 22402599
TI  - Effects of recombinant human endostatin and its synergy with cisplatin on
      circulating endothelial cells and tumor vascular normalization in A549 xenograft
      murine model.
AB  - PURPOSE: Endostatin can normalize the tumor vasculature to some extent. However,
      exact length of its time window and corresponding markers for tumor vascular
      normalization are needed to be explored. METHODS: The A549 lung adenocarcinoma
      xenograft murine model was treated with recombinant human endostatin (rh
      endostatin) for 14 days. Cisplatin was combined in different schedules. The
      effects of rh-endostatin on circulating endothelial cells (CECs) by flow
      cytometry, tumor vasculature and angiogenesis-related factors by confocal
      microscope and immunohistochemistry, and anti-tumor efficacy of cytotoxic drugs
      were observed. RESULTS: The activated CECs (aCECs) were increased on day 7 and
      decreased on day 10, and apoptotic CECs were increased on day 10. Tumor
      vasculature was transiently normalized with increased collagen coverage,
      decreased vessel permeability, intratumoral hypoxia, and microvascular density
      from day 7 to 10 after rh-endostatin administration. Extracellular matrix
      metalloproteinase inducer, vascular endothelial growth factor, matrix
      metalloproteinase (MMP)-2, and MMP-9 were transiently decreased by rh-endostatin
      from day 4 to 10, whereas the opposite effects were observed with tissue
      inhibitors of matrix metalloproteinase (TIMP)-1 and TIMP-2. The maximal anti
      tumor effects of cisplatin were observed on administration from day 5 to 9 after
      rh-endostatin initial administration. CONCLUSIONS: Rh-endostatin could
      transiently normalize tumor vasculature, probably via regulation of both pro- and
      anti-angiogenesis factors. The synergistic efficacy of anti-angiogenesis and
      chemotherapy was found during "the normalization window". CEC could be a feasible
      blood biomarker for defining "vascular normalization window" and providing the
      evidence to make an optimizing combination therapeutic schedule in human tumor.

PMID- 22402601
TI  - Caspase cleavage of viral proteins, another way for viruses to make the best of
      apoptosis.
AB  - Viral infection constitutes an unwanted intrusion that needs to be eradicated by
      host cells. On one hand, one of the first protective barriers set up to prevent
      viral replication, spread or persistence involves the induction of apoptotic cell
      death that aims to limit the availability of the cellular components for viral
      amplification. On the other hand, while they completely depend on the host
      molecular machinery, viruses also need to evade the cellular responses that are
      meant to destroy them. The existence of numerous antiapoptotic products within
      the viral kingdom proves that apoptosis constitutes a major threat that should
      better be bypassed. Among the different strategies developed to deal with
      apoptosis, one is based on what viruses do best: backfiring the cell on itself.
      Several unrelated viruses have been described to take advantage of apoptosis
      induction by expressing proteins targeted by caspases, the key effectors of
      apoptotic cell death. Caspase cleavage of these proteins results in various
      consequences, from logical apoptosis inhibition to more surprising enhancement or
      attenuation of viral replication. The present review aims at discussing the
      characterization and relevance of this post-translational modification that adds
      a new complexity in the already intricate host-apoptosis-virus triangle.

PMID- 22402602
TI  - Synchronized ATP oscillations have a critical role in prechondrogenic
      condensation during chondrogenesis.
AB  - The skeletal elements of embryonic limb are prefigured by prechondrogenic
      condensation in which secreted molecules such as adhesion molecules and
      extracellular matrix have crucial roles. However, how the secreted molecules are
      controlled to organize the condensation remains unclear. In this study, we
      examined metabolic regulation of secretion in prechondrogenic condensation, using
      bioluminescent monitoring systems. We here report on ATP oscillations in the
      early step of chondrogenesis. The ATP oscillations depended on both glycolysis
      and mitochondrial respiration, and their synchronization among cells were
      achieved via gap junctions. In addition, the ATP oscillations were driven by
      Ca(2+) oscillations and led to oscillatory secretion in chondrogenesis. Blockade
      of the ATP oscillations prevented cellular condensation. Furthermore, the degree
      of cellular condensation increased with the frequency of ATP oscillations. We
      conclude that ATP oscillations have a critical role in prechondrogenic
      condensation by inducing oscillatory secretion.

PMID- 22402604
TI  - Trunk, pelvis, hip, and knee kinematics, hip strength, and gluteal muscle
      activation during a single-leg squat in males and females with and without
      patellofemoral pain syndrome.
AB  - STUDY DESIGN: Controlled laboratory study using a cross-sectional design.
      OBJECTIVES: To determine whether there are any differences between the sexes in
      trunk, pelvis, hip, and knee kinematics, hip strength, and gluteal muscle
      activation during the performance of a single-leg squat in individuals with
      patellofemoral pain syndrome (PFPS) and control participants. BACKGROUND: Though
      there is a greater incidence of PFPS in females, PFPS is also quite common in
      males. Trunk kinematics may affect hip and knee function; however, there is a
      lack of studies of the influence of the trunk in individuals with PFPS. METHODS:
      Eighty subjects were distributed into 4 groups: females with PFPS, female
      controls, males with PFPS, and male controls. Trunk, pelvis, hip, and knee
      kinematics and gluteal muscle activation were evaluated during a single-leg
      squat. Hip abduction and external rotation eccentric strength was measured on an
      isokinetic dynamometer. Group differences were assessed using a 2-way
      multivariate analysis of variance (sex by PFPS status). RESULTS: Compared to
      controls, subjects with PFPS had greater ipsilateral trunk lean (mean +/- SD, 9.3
      degrees  +/- 5.3 degrees  versus 6.7 degrees  +/- 3.0 degrees ; P = .012),
      contralateral pelvic drop (10.3 degrees  +/- 4.7 degrees  versus 7.4 degrees  +/-
      3.8 degrees ; P = .003), hip adduction (14.8 degrees  +/- 7.8 degrees  versus
      10.8 degrees  +/- 5.6 degrees ; P<.0001), and knee abduction (9.2 degrees  +/-
      5.0 degrees  versus 5.8 degrees  +/- 3.4 degrees ; P<.0001) when performing a
      single-leg squat. Subjects with PFPS also had 18% less hip abduction and 17% less
      hip external rotation strength. Compared to female controls, females with PFPS
      had more hip internal rotation (P<.05) and less muscle activation of the gluteus
      medius (P = .017) during the single-leg squat. CONCLUSION: Despite many
      similarities in findings for males and females with PFPS, there may be specific
      sex differences that warrant consideration in future studies and when clinically
      evaluating and treating females with PFPS.

PMID- 22402603
TI  - IGL-1 solution reduces endoplasmic reticulum stress and apoptosis in rat liver
      transplantation.
AB  - Injury due to cold ischemia reperfusion (I/R) is a major cause of primary graft
      non-function following liver transplantation. We postulated that I/R-induced
      cellular damage during liver transplantation might affect the secretory pathway,
      particularly at the endoplasmic reticulum (ER). We examined the involvement of ER
      stress in organ preservation, and compared cold storage in University of
      Wisconsin (UW) solution and in Institute Georges Lopez-1 (IGL-1) solution. In one
      group of rats, livers were preserved in UW solution for 8 h at 4  degrees C, and
      then orthotopic liver transplantation was performed according to Kamada's cuff
      technique. In another group, livers were preserved in IGL-1 solution. The effect
      of each preservation solution on the induction of ER stress, hepatic injury,
      mitochondrial damage and cell death was evaluated. As expected, we found
      increased ER stress after liver transplantation. IGL-1 solution significantly
      attenuated ER damage by reducing the activation of three pathways of unfolded
      protein response and their effector molecules caspase-12, C/EBP homologous
      protein-10, X-box-binding protein 1, tumor necrosis factor-associated factor 2
      and eukaryotic translation initiation factor 2. This attenuation of ER stress was
      associated with a reduction in hepatic injury and cell death. Our results show
      that IGL-1 solution may be a useful means to circumvent excessive ER stress
      reactions associated with liver transplantation, and may optimize graft quality.

PMID- 22402605
TI  - Fermi energy level tuning for high performance dye sensitized solar cells using
      sp2 selective nitrogen-doped carbon nanotube channels.
AB  - Here, we find that doping sp(2) selective nitrogen, N sp(2), into carbon nanotube
      (CNT) channels induces a positive shift in the Fermi level of TiO(2)
      photoelectrodes. It is found that this results in the large diffusion coefficient
      of solar driven electrons for increasing the photocurrent as well as in the low
      recombination rate for improving open circuit voltage with 0.74 V, which could
      not be overcome by using pristine CNT channels with 0.66 V.

PMID- 22402606
TI  - An emerging cell-based strategy in orthopaedics: endothelial progenitor cells.
AB  - PURPOSE: The purpose of this article was to analyze the results of studies in the
      literature, which evaluated the use of endothelial progenitor cells (EPCs) as a
      cell-based tissue engineering strategy. METHODS: EPCs have been successfully used
      in regenerative medicine to augment neovascularization in patients after
      myocardial infarction and limb ischemia. EPCs' important role as vasculogenic
      progenitors presents them as a potential source for cell-based therapies to
      promote bone healing. RESULTS: EPCs have been shown to have prominent effects in
      promoting bone regeneration in several animal models. Evidence indicates that
      EPCs promote bone regeneration by stimulating both angiogenesis and osteogenesis
      through a differentiation process toward endothelial cell lineage and formation
      of osteoblasts. Moreover, EPCs increase vascularization and osteogenesis by
      increased secretion of growth factors and cytokines through paracrine mechanisms.
      CONCLUSION: EPCs offer the potential to emerge as a new strategy among other cell
      based therapies to promote bone regeneration. Further investigations and human
      trials are required to address current questions with regard to biology and
      mechanisms of action of EPCs in bone tissue engineering.

PMID- 22402607
TI  - SKLB1028, a novel oral multikinase inhibitor of EGFR, FLT3 and Abl, displays
      exceptional activity in models of FLT3-driven AML and considerable potency in
      models of CML harboring Abl mutants.

PMID- 22402608
TI  - Acoustofluidics 9: Modelling and applications of planar resonant devices for
      acoustic particle manipulation.
AB  - This article introduces the design, construction and applications of planar
      resonant devices for particle and cell manipulation. These systems rely on the
      pistonic action of a piezoelectric layer to generate a one dimensional axial
      variation in acoustic pressure through a system of acoustically tuned layers. The
      resulting acoustic standing wave is dominated by planar variations in pressure
      causing particles to migrate to planar pressure nodes (or antinodes depending on
      particle and fluid properties). The consequences of lateral variations in the
      fields are discussed, and rules for designing resonators with high energy density
      within the appropriate layer for a given drive voltage presented.

PMID- 22402609
TI  - Saliva and sera IgA and IgG in Egyptian Giardia-infected children.
AB  - Giardiasis is a gastrointestinal infection of wide distribution that is more
      prevalent in childhood. Easy and rapid diagnosis of giardiasis is essential for
      reduction of this infection. This cross-sectional study included 62 children in
      which collection of saliva, stool and serum samples was performed. An enzyme
      linked immunosorbent assay (ELISA) technique was evaluated to detect IgA and IgG
      responses in both saliva and serum samples. Twenty-two children were positive for
      Giardia duodenalis infection by direct examination of faecal specimens, 20 non
      infected and 20 infected with other parasites. Salivary and serum IgA and IgG
      responses against G. duodenalis infection were significantly higher in Giardia
      parasitized than non-Giardia parasitized children (p < 0.001). This concludes
      that specific salivary IgA may serve as a diagnostic tool and specific salivary
      IgG as a screening tool in monitoring the exposure of various populations to
      Giardia duodenalis. The advantage of salivary assays over serum immunoglobulin
      assay is being easy and non-invasive in sampling technique which is important
      especially for young children.

PMID- 22402610
TI  - Cloning and characterization of high mobility group box protein 1 (HMGB1) of
      Wuchereria bancrofti and Brugia malayi.
AB  - A human homologue of high mobility group box 1 (HMGB1) protein was cloned and
      characterized from the human filarial parasites Wuchereria bancrofti and Brugia
      malayi. Sequence analysis showed that W. bancrofti HMGB1 (WbHMGB1) and B. malayi
      HMGB1 (BmHMGB1) proteins share 99 % sequence identity. Filarial HMGB1 showed
      typical architectural sequence characteristics of HMGB family of proteins and
      consisted of only a single HMG box domain that had significant sequence
      similarity to the pro-inflammatory B box domain of human HMGB1. When incubated
      with mouse peritoneal macrophages and human promyelocytic leukemia cells,
      rBmHMGB1 induced secretion of significant levels of pro-inflammatory cytokines
      such as TNF-alpha, GM-CSF, and IL-6. Functional analysis also showed that the
      filarial HMGB1 proteins can bind to supercoiled DNA similar to other HMG family
      of proteins. BmHMGB1 protein is expressed in the adult and microfilarial stages
      of the parasite and is found in the excretory secretions of the live parasites.
      These findings suggest that filarial HMGB1 may have a significant role in
      lymphatic pathology associated with lymphatic filariasis.

PMID- 22402611
TI  - Acute promyelocytic leukemia with trisomy 8 showing normal PML-RARA FISH signal
      patterns: diagnostic application of long-distance polymerase chain reaction in
      molecularly discrepant leukemia cases.

PMID- 22402612
TI  - rehh: an R package to detect footprints of selection in genome-wide SNP data from
      haplotype structure.
AB  - With the development of next-generation sequencing and genotyping approaches,
      large single nucleotide polymorphism haplotype datasets are becoming available in
      a growing number of both model and non-model species. Identifying genomic regions
      with unexpectedly high local haplotype homozygosity relatively to neutral
      expectation represents a powerful strategy to ascertain candidate genes
      responding to natural or artificial selection. To facilitate genome-wide scans of
      selection based on the analysis of long-range haplotypes, we developed the R
      package rehh. It provides a versatile tool to detect the footprints of recent or
      ongoing selection with several graphical functions that help visual
      interpretation of the results. AVAILABILITY AND IMPLEMENTATION: Stable version is
      available from CRAN: http://cran.r-project.org/. Development version is available
      from the R-forge repository: http://r-forge.r-project.org/projects/rehh. Both
      versions can be installed directly from R. Function documentation and example
      data files are provided within the package and a tutorial is available as
      Supplementary Material. rehh is distributed under the GNU General Public Licence
      (GPL >= 2).

PMID- 22402613
TI  - A strategy for building neuroanatomy ontologies.
AB  - MOTIVATION: Advancing our understanding of how nervous systems work will require
      the ability to store and annotate 3D anatomical datasets, recording morphology,
      partonomy and connectivity at multiple levels of granularity from subcellular to
      gross anatomy. It will also require the ability to integrate this data with other
      data-types including functional, genetic and electrophysiological data. The web
      ontology language OWL2 provides the means to solve many of these problems. Using
      it, one can rigorously define and relate classes of anatomical structure using
      multiple criteria. The resulting classes can be used to annotate datasets
      recording, for example, gene expression or electrophysiology. Reasoning software
      can be used to automate classification and error checking and to construct and
      answer sophisticated combinatorial queries. But for such queries to give
      consistent and biologically meaningful results, it is important that both classes
      and the terms (relations) used to relate them are carefully defined. RESULTS: We
      formally define a set of relations for recording the spatial and connectivity
      relationships of neuron classes and brain regions in a broad range of species,
      from vertebrates to arthropods. We illustrate the utility of our approach via its
      application in the ontology that drives the Virtual Fly Brain web resource.
      AVAILABILITY AND IMPLEMENTATION: The relations we define are available from
      http://purl.obolibrary.org/obo/ro.owl. They are used in the Drosophila anatomy
      ontology (http://purl.obolibrary.org/obo/fbbt/2011-09-06/), which drives the web
      resource http://www.virtualflybrain.org

PMID- 22402614
TI  - YOABS: yet other aligner of biological sequences--an efficient linearly scaling
      nucleotide aligner.
AB  - MOTIVATION: Explosive growth of short-read sequencing technologies in the recent
      years resulted in rapid development of many new alignment algorithms and
      programs. But most of them are not efficient or not applicable for reads > or
      approximately equal to 200 bp because these algorithms specifically designed to
      process short queries with relatively low sequencing error rates. However, the
      current trend to increase reliability of detection of structural variations in
      assembled genomes as well as to facilitate de novo sequencing demand
      complimenting high-throughput short-read platforms with long-read mapping. Thus,
      algorithms and programs for efficient mapping of longer reads are becoming
      crucial. However, the choice of long-read aligners effective in terms of both
      performance and memory are limited and includes only handful of hash table (BLAT,
      SSAHA2) or trie (Burrows-Wheeler Transform - Smith-Waterman (BWT-SW), Burrows
      Wheeler Alignerr - Smith-Waterman (BWA-SW)) based algorithms. RESULTS: New O(n)
      algorithm that combines the advantages of both hash and trie-based methods has
      been designed to effectively align long biological sequences (> or approximately
      equal to 200 bp) against a large sequence database with small memory footprint
      (e.g. ~2 GB for the human genome). The algorithm is accurate and significantly
      more fast than BLAT or BWT-SW, but similar to BWT-SW it can find all local
      alignments. It is as accurate as SSAHA2 or BWA-SW, but uses 3+ times less memory
      and 10+ times faster than SSAHA2, several times faster than BWA-SW with low error
      rates and almost two times less memory. AVAILABILITY AND IMPLEMENTATION: The
      prototype implementation of the algorithm will be available upon request for non
      commercial use in academia (local hit table binary and indices are at
      ftp://styx.ucsd.edu).

PMID- 22402615
TI  - The importance of p-n junction interfaces for efficient small molecule-based
      organic solar cells.
AB  - The efficiency of small-molecule solar cells critically depends on the match of
      the junction of the donor and acceptor semiconductors used in these devices to
      create charged carriers and on the mobility of individual components to transport
      holes and electrons. In the present study, a 2% efficient bilayer organic solar
      cell consisting of a p-type semiconductor, pentacene, and an n-type
      semiconductor, N,N'-diheptyl-3,4,9,10-perylenetetracarboxylic diimide (PTCDI
      C(7)), is fabricated. The morphology of PTCDI-C(7) interestingly follows
      pentacene due to the matched surface energy of these two active layers and the
      easily deposited PTCDI-C(7) monomers on an inclined plane of the pentacene
      grains. This condition results in the low trap states in the PTCDI-C(7) film and
      at the pentacene/PTCDI-C(7) interface for the enhancement of exciton dissociation
      and carrier transport compared with the photoactive layer comprised of pentacene
      and N,N-ditridecyl-3,4,9,10-perylenetetracarboxylic diimide (PTCDI-C(13)). The
      detailed exciton and carrier transport mechanisms are investigated using time
      resolved photoluminescence and X-ray diffraction spectroscopy.

PMID- 22402616
TI  - Organocatalytic enantioselective Michael addition of a kojic acid derivative to
      nitro olefins.
AB  - By employing a chiral bifunctional thiourea-tertiary amine as catalyst,
      enantioselective Michael addition of a kojic acid derivative to nitro olefins was
      realised. The reactions afforded the products with good yields (up to 99%) in
      good enantioselectivities (up to 97% ee). In addition, the absolute configuration
      of one product was determined.

PMID- 22402618
TI  - Periodontal findings and platelet parameters.

PMID- 22402617
TI  - Clinical and microbiological evaluation of high intensity diode laser adjutant to
      non-surgical periodontal treatment: a 6-month clinical trial.
AB  - OBJECTIVES: This randomized split-mouth clinical trial was designed to evaluate
      the efficacy of scaling and root planing associated to the high-intensity diode
      laser on periodontal therapy by means of clinical parameters and microbial
      reduction. MATERIALS AND METHODS: A total of 36 chronic periodontitis subjects,
      of both genders, were selected. One pair of contralateral single-rooted teeth
      with pocket depth >5 mm was chosen from each subject. All patients received non
      surgical periodontal treatment, after which the experimental teeth were
      designated to either test or control groups. Both teeth received scaling, root
      planing and coronal polishing (SRP) and teeth assigned to the test group (SRP +
      DL) were irradiated with the 808 +/- 5 nm diode laser, for 20 s, in two isolated
      appointments, 1 week apart. The laser was used in the continuous mode, with 1.5 W
      and power density of 1,193.7 W/cm(2). Clinical and microbiological data were
      collected at baseline, 6 weeks and 6 months after therapy. RESULTS: There was a
      significant improvement of all the clinical parameters-clinical attachment level
      (CAL), probing depth (PD), plaque index (PI) and Bleeding on Probing (BOP)-for
      both groups (P < 0.001), with no statistical difference between them at the 6
      weeks and the 6 months examinations. As for microbiological analysis, a
      significant reduction after 6 weeks (P > 0.05) was observed as far as colony
      forming units (CFU) is concerned, for both groups. As for black-pigmented
      bacteria, a significant reduction was observed in both groups after 6 months.
      However, the difference between test and control groups was not significant.
      There was no association between group and presence of Porphyromonas gingivalis,
      Prevotella intermedia and Aggregatibacter actinomycetemcomitans at any time of
      the study. CONCLUSIONS: After 6 months of evaluation, the high-intensity diode
      laser has not shown any additional benefits to the conventional periodontal
      treatment. CLINICAL RELEVANCE: The high intensity diode laser did not provide
      additional benefits to non-surgical periodontal treatment. More studies are
      necessary to prove the actual need of this type of laser in the periodontal
      clinical practice.

PMID- 22402620
TI  - Energy transfer from a rhodamine antenna to a ruthenium-bipyridine center.
AB  - The coordination of a modified rhodamine B (Rhod) to a bis-bipyridine ruthenium
      (ii) (Ru-bpy) phototrigger complex enables a photodissociation reaction at longer
      wavelengths through enhanced absorption of green light (532 nm). The very high
      molar absorptivity of rhodamine (~10(5) M(-1) cm(-1)) and the high quantum
      efficiency of Forster resonance energy transfer (FRET) from rhodamine to the Ru
      bpy center (0.84) result in an unusually high photosensitivity and uncaging cross
      section of the Ru-bpy-rhodamine complex at longer wavelengths. 

PMID- 22402621
TI  - Evolutionary indirect effects of biological invasions.
AB  - Just as ecological indirect effects can have a wide range of consequences for
      community structure and ecosystem function, theory suggests that evolutionary
      indirect effects can also influence community dynamics and the outcome of species
      interactions. There is little empirical evidence documenting such effects,
      however. Here, I use a multi-generation selection experiment in the field to
      investigate: (1) how the exotic plant Medicago polymorpha and the exotic insect
      herbivore Hypera brunneipennis affect the evolution of anti-herbivore resistance
      traits in the native plant Lotus wrangelianus and (2) how observed Lotus
      evolutionary responses to Hypera alter interactions between Lotus and other
      members of the herbivore community. In one of two study populations, I document
      rapid evolutionary changes in Lotus resistance to Hypera in response to
      insecticide treatments that experimentally reduced Hypera abundance, and in
      response to Medicago-removal treatments that also reduced Hypera abundance. These
      evolutionary changes in response to Hypera result in reduced attack by aphids.
      Thus, an evolutionary change caused by one herbivore species alters interactions
      with other herbivore taxa, an example of an eco-evolutionary feedback. Given that
      many traits mediate interactions with multiple species, the effects of
      evolutionary changes in response to one key biotic selective agent may often
      cascade through interaction webs to influence additional community members.

PMID- 22402622
TI  - Are host-parasite interactions influenced by adaptation to predators? A test with
      guppies and Gyrodactylus in experimental stream channels.
AB  - Natural populations often face multiple mortality sources. Adaptive responses to
      one mortality source might also be beneficial with respect to other sources of
      mortality, resulting in "reinforcing adaptations"; or they might be detrimental
      with respect to other sources of mortality, resulting in "conflicting
      adaptations". We explored these possibilities by testing experimentally if the
      responses of guppies (Poecilia reticulata) to the monogenean ectoparasitic worm
      Gyrodactylus differed between populations adapted to different predation regimes.
      In experimental stream channels designed to replicate the natural environment, we
      exposed eight guppy populations (high-predation and low-predation populations
      from each of four separate rivers) either to their local Gyrodactylus parasites
      (infection treatment) or to the absence of those parasites (control). We found
      that infection dynamics varied dramatically among populations in a repeatable
      fashion, but that this variation was not related to the predation regime of
      origin. Consistent with previous work, high-predation guppy females gained more
      mass, had lower reproductive investment, and had more but smaller embryos than
      did low-predation females. Relative to control (no parasite) channels, guppies
      from treatment (infected) channels gained less mass but produced similar numbers
      and sizes of embryos-and thus had a higher reproductive effort. However, no
      interaction was evident between infection treatment and predation regime. We
      conclude that parasitism by Gyrodactylus and predation are both likely selective
      forces for guppies, but that adaptation to predation does not have an obvious
      deterministic effect on host-parasite dynamics or on life-history traits of
      female guppies.

PMID- 22402623
TI  - An artificially constructed radiation-responsive promoter is activated by
      doxorubicin.
AB  - We previously developed an artificially constructed promoter that was activated
      in response to X-ray irradiation in LNCap, a prostate cancer cell line.
      Anticancer drugs were examined to see whether some of them could stimulate the
      activity of the promoter. It was found that doxorubicin (Dox) treatment to LNCap
      transfected with a gene cassette of the luciferase gene under control of the
      promoter-enhanced luciferase activity in a dose-dependent manner, indicating that
      the promoter could be controlled by Dox. When the luciferase gene was replaced
      with the fcy::fur gene whose product facilitates conversion of 5-fluorocytosine
      into 5-fluorouracil that is highly toxic, Dox stimulated the expression of the
      gene product, resulting in facilitation of cell killing effect in the presence of
      5-fluorocytosine. These results suggest that therapeutic gene expression
      controlled with an anticancer drug may lead to a more effective cancer therapy
      with less hazardous side effects.

PMID- 22402624
TI  - Intratumoral delivery of CD154 homolog (Ad-ISF35) induces tumor regression:
      analysis of vector biodistribution, persistence and gene expression.
AB  - Ad-ISF35 is an adenovirus (Ad) vector that encodes a mouse-human chimeric CD154.
      Ad-ISF35 induces activation of chronic lymphocytic leukemia (CLL) cells
      converting them into CLL cells capable of promoting immune recognition and anti
      leukemia T-cell activation. Clinical trials in humans treated with Ad-ISF35
      transduced leukemia cells or intranodal injection of Ad-ISF35 have shown
      objective clinical responses. To better understand the biology of Ad-ISF35 and to
      contribute to its clinical development, we preformed studies to evaluate
      biodistribution, persistence and toxicity of repeat dose intratumoral
      administration of Ad-ISF35 in a mouse model. Ad-ISF35 intratumoral administration
      induced tumor regression in more than 80% of mice bearing A20 tumors. There were
      no abnormalities in the serum chemistry. Mice receiving Ad-ISF35 presented severe
      extramedullary hematopoiesis and follicular hyperplasia in the spleen and
      extramedullary hematopoiesis with lymphoid hyperplasia in lymph nodes. After Ad
      ISF35 injection, the vector was found primarily in the injected tumors with a
      biodistribution pattern that showed a rapid clearance with no evidence of Ad
      ISF35 accumulation or persistence in the injected tumor or peripheral organs.
      Furthermore, pre-existing antibodies against Ad-5 did not abrogate Ad-ISF35 anti
      tumor activity. In conclusion, intratumoral administration of Ad-ISF35 induced
      tumor regression in A20 tumor bearing mice without toxicities and with no
      evidence of vector accumulation or persistence.

PMID- 22402625
TI  - Membrane-bound form of monocyte chemoattractant protein-1 enhances antitumor
      effects of suicide gene therapy in a model of hepatocellular carcinoma.
AB  - Suicide gene therapy using the herpes simplex virus thymidine kinase/ganciclovir
      (HSV-tk/GCV) system combined with monocyte chemoattractant protein-1 (MCP-1)
      provides significant antitumor efficacy. The current study was designed to
      evaluate the antitumor immunity of a newly developed membrane-bound form of MCP-1
      (mMCP-1) in an immunocompetent mouse model of hepatocellular carcinoma (HCC). A
      recombinant adenovirus vector (rAd) harboring the human MCP-1 gene and the
      membrane-spanning domain of the CX3CL1 gene was used. Large amounts of MCP-1
      protein were expressed and accumulated on the tumor cell surface. The growth of
      subcutaneous tumors was markedly suppressed when tumors were treated with mMCP-1,
      as compared with soluble MCP-1, in combination with the HSV-tk/GCV system
      (P<0.01). The numbers of Mac-1-, CD4- and CD8a-positive cells were significantly
      higher in tumor tissues (P<0.05), and tumor necrosis factor (TNF) mRNA expression
      levels with mMCP-1 were almost five-fold higher than those with soluble MCP-1.
      These results indicate that the delivery of the mMCP-1 gene greatly enhanced
      antitumor effects following the apoptotic stimuli by promoting the recruitment
      and activation of macrophages and T lymphocytes, suggesting a novel strategy of
      immune-based gene therapy in the treatment of patients with HCC.

PMID- 22402626
TI  - Induced transgene expression for the treatment of solid tumors by hematopoietic
      stem cell-based gene therapy.
AB  - Tumor microenvironment is composed of different cell types including immune
      cells. Far from acting to eradicate cancer cells, these bone marrow-derived
      components could be involved in carcinogenesis and/or tumor invasion and
      metastasis. Here, we describe an alternative approach to treat solid tumors based
      on the genetic modification of hematopoietic stem and progenitor cells with
      lentiviral vectors. To achieve transgene expression in derivative tumor
      infiltrating leukocytes and to try to decrease systemic toxicity, we used the
      stress inducible human HSP70B promoter. Functionality of the promoter was
      characterized in vitro using hyperthermia. Antitumor efficacy was assessed by ex
      vivo genetic modification of lineage-negative cells with lentiviral vectors
      encoding the dominant-negative mutant of the human transforming growth factor
      beta receptor II (TbetaRIIDN) driven by the HSP70B promoter, and reinfusion of
      cells into recipient mice. Subsequently, syngeneic GL261 glioma cells were
      subcutaneously injected into bone marrow-transplanted mice. As a result, a
      massive antitumor response was observed in mice harboring TbetaRIIDN under the
      HSP70B promoter, without the need of any external source of stress. In summary,
      this study shows that stem cell-based gene therapy in combination with spatial
      and temporal control of transgene expression in derivative tumor-infiltrating
      cells represents an alternative strategy for the development of novel antitumor
      therapies.

PMID- 22402627
TI  - Potential use of folate-polyethylene glycol (PEG)-appended dendrimer (G3)
      conjugate with alpha-cyclodextrin as DNA carriers to tumor cells.
AB  - We previously reported that polyamidoamine STARBURST dendrimer (generation 3, G3)
      (dendrimer) conjugate with alpha-cyclodextrin (alpha-CyD) having an average
      degree of substitution of 2.4 of alpha-CyD (alpha-CDE) provided remarkable
      aspects as novel carriers for DNA and small-interfering RNA. To develop novel
      alpha-CDE derivatives with tumor cell specificity, we prepared folate-appended
      alpha-CDEs (Fol-alpha-CDEs) and folate-polyethylene glycol (PEG)-appended alpha
      CDEs (Fol-PalphaCs) with the various degrees of substitution of folate (DSF), and
      evaluated in vitro and in vivo gene transfer activity, cytotoxicity, cellular
      association and physicochemical properties. In vitro gene transfer activity of
      Fol-alpha-CDEs (G3, DSF 2, 5 or 7) was lower than that of alpha-CDE (G3) in KB
      cells, folate receptor (FR)-overexpressing cancer cells. Of the three Fol
      PalphaCs (G3, DSF 2, 5 or 7), Fol-PalphaC (G3, DSF 5) had the highest gene
      transfer activity in KB cells. The activity of Fol-PalphaC (G3, DSF 5) was
      significantly higher than that of alpha-CDE (G3) in KB cells, but not in A549
      cells, FR-negative cells. Negligible cytotoxicity of the plasmid DNA (pDNA)
      complex with Fol-PalphaC (G3, DSF 5) was observed in KB cells or A549 cells up to
      a charge ratio of 100/1 (carrier/pDNA). The cellular association of the pDNA
      complex with Fol-PalphaC (G3, DSF 5) could be mediated by FR on KB cells,
      resulting in its efficient cellular uptake. Fol-PalphaC (G3, DSF 5) had a higher
      binding affinity with folate-binding protein than alpha-CDE (G3), although the
      physicochemical properties of pDNA complex with Fol-PalphaC (G3, DSF 5) were
      almost comparable to that with alpha-CDE (G3), although the onset charge ratio
      and the compaction ability of Fol-PalphaC (G3, DSF 5) were slightly different.
      Fol-PalphaC (G3, DSF 5) tended to show a higher gene transfer activity than alpha
      CDE (G3) 12 h after intratumoral administration in mice. These results suggest
      that Fol-PalphaC (G3, DSF 5), not Fol-alpha-CDEs, could be potentially used as a
      FR-overexpressing cancer cell-selective DNA carrier.

PMID- 22402628
TI  - Experimental validation of plugging during drop formation in a T-junction.
AB  - At low capillary number, drop formation in a T-junction is dominated by
      interfacial effects: as the dispersed fluid flows into the drop maker nozzle, it
      blocks the path of the continuous fluid; this leads to a pressure rise in the
      continuous fluid that, in turn, squeezes on the dispersed fluid, inducing pinch
      off of a drop. While the resulting drop volume predicted by this "squeezing"
      mechanism has been validated for a range of systems, as of yet, the pressure rise
      responsible for the actual pinch-off has not been observed experimentally. This
      is due to the challenge of measuring the pressures in a T-junction with the
      requisite speed, accuracy, and localization. Here, we present an empirical study
      of the pressures in a T-junction during drop formation. Using Laplace sensors,
      pressure probes we have developed, we confirm the central ideas of the squeezing
      mechanism; however, we also uncover other findings, including that the pressure
      of the dispersed fluid is not constant but rather oscillates in anti-phase with
      that of the continuous fluid. In addition, even at the highest capillary number
      for which monodisperse drops can be formed, pressure oscillations persist,
      indicating that drop formation in confined geometries does not transition to an
      entirely shear-driven mechanism, but to a mechanism combining squeezing and
      shearing.

PMID- 22402629
TI  - New insights into the interface between a single-crystalline metal electrode and
      an extremely pure ionic liquid: slow interfacial processes and the influence of
      temperature on interfacial dynamics.
AB  - Ionic liquids are of high interest for the development of safe electrolytes in
      modern electrochemical cells, such as batteries, supercapacitors and dye
      sensitised solar cells. However, electrochemical applications of ionic liquids
      are still hindered by the limited understanding of the interface between
      electrode materials and ionic liquids. In this article, we first review the state
      of the art in both experiment and theory. Then we illustrate some general trends
      by taking the interface between the extremely pure ionic liquid 1-butyl-1
      methylpyrrolidinium tris(pentafluoroethyl)trifluorophosphate and an Au(111)
      electrode as an example. For the study of this interface, electrochemical
      impedance spectroscopy was combined with in situ STM and in situ AFM techniques.
      In addition, we present new results for the temperature dependence of the
      interfacial capacitance and dynamics. Since the interfacial dynamics are
      characterised by different processes taking place on different time scales, the
      temperature dependence of the dynamics can only be reliably studied by recording
      and carefully analysing broadband capacitance spectra. Single-frequency
      experiments may lead to artefacts in the temperature dependence of the
      interfacial capacitance. We demonstrate that the fast capacitive process exhibits
      a Vogel-Fulcher-Tamman temperature dependence, since its time scale is governed
      by the ionic conductivity of the ionic liquid. In contrast, the slower capacitive
      process appears to be Arrhenius activated. This suggests that the time scale of
      this process is determined by a temperature-independent barrier, which may be
      related to structural reorganisations of the Au surface and/or to charge
      redistributions in the strongly bound innermost ion layer.

PMID- 22402630
TI  - (S)-Proline-catalyzed nitro-Michael reactions: towards a better understanding of
      the catalytic mechanism and enantioselectivity.
AB  - (S)-Proline-catalyzed nitro-Michael additions of aldehydes and ketones to beta
      nitrostyrene were investigated computationally (MP2/6-311+G**//M06-2X/6-31G**).
      Contrary to what is usually assumed in organocatalysis, the lowest-energy
      transition states of proline-catalyzed nitro-Michael reactions do not necessarily
      involve the carboxylic acid group of the proline moiety directing the incoming
      nitroalkene to the same face through hydrogen bonding. For the aldehyde
      substrates examined, the TS leading to the major (R,S) product was found to
      involve the anti-enamine and nitroalkene approaching from the opposite face of
      the carboxyl group. In the case of ketone substrates, the lowest-energy TSs
      leading to both enantiomeric products are characterized by the absence of
      hydrogen bonds and s-cis conformation of the carboxyl group, which functions as
      an electron donor to stablize the developing iminium. When both hydrogen bonded
      and non-hydrogen bonded types of TSs are considered, the calculated
      enantioselectivities for Michael additions of aldehyde and ketone substrates are
      in good agreement with experimental findings.

PMID- 22402631
TI  - Hydrostatic and boundary lubrication of joints--nature of boundary lubricant.
AB  - A very low coefficient of friction in joints makes it difficult to define clearly
      the mechanism of cartilage lubrication. The present paper describes the two
      currently predominant and mutually complementary views aiming to elucidate this
      mechanism. The first mechanism, referred to as hydrostatic lubrication, involves
      interstitial fluid pressurization from the cartilage and its importance for the
      formation of a layer separating the weight-bearing surfaces. The second
      mechanism, called boundary lubrication, assumes the existence of a substance that
      binds to the cartilage surface, permanently separating the friction elements. It
      has not been clearly determined which substances occurring in the synovial fluid
      function as boundary lubricants. The authors briefly describe the physicochemical
      properties of lubricin, surface-active phospholipids and hyaluronic acid,
      including their role in boundary lubrication.

PMID- 22402632
TI  - Methylome analysis using MeDIP-seq with low DNA concentrations.
AB  - DNA methylation is an epigenetic mark that has a crucial role in many biological
      processes. To understand the functional consequences of DNA methylation on
      phenotypic plasticity, a genome-wide analysis should be embraced. This in turn
      requires a technique that balances accuracy, genome coverage, resolution and
      cost, yet is low in DNA input in order to minimize the drain on precious samples.
      Methylated DNA immunoprecipitation-sequencing (MeDIP-seq) fulfils these criteria,
      combining MeDIP with massively parallel DNA sequencing. Here we report an
      improved protocol using 100-fold less genomic DNA than that commonly used. We
      show comparable results for specificity (>97%) and enrichment (>100-fold) over a
      wide range of DNA concentrations (5,000-50 ng) and demonstrate the utility of the
      protocol for the generation of methylomes from rare bone marrow cells using 160
      300 ng of starting DNA. The protocol described here, i.e., DNA extraction to
      generation of MeDIP-seq library, can be completed within 3-5 d.

PMID- 22402633
TI  - Mouse model of oropharyngeal candidiasis.
AB  - Oropharyngeal candidiasis is a frequent cause of morbidity in patients with
      defects in cell-mediated immunity or saliva production. Animal models of this
      infection are important for studying disease pathogenesis and evaluating vaccines
      and antifungal therapies. Here we describe a simple mouse model of oropharyngeal
      candidiasis. Mice are rendered susceptible to oral infection by injection with
      cortisone acetate and then inoculated by placing a swab saturated with Candida
      albicans sublingually. This process results in a reproducible level of infection,
      the histopathology of which mimics that of pseudomembranous oropharyngeal
      candidiasis in humans. By using this model, data are obtained after 5-9 d of
      work.

PMID- 22402634
TI  - Nicking enzyme-based internal labeling of DNA at multiple loci.
AB  - The labeling of biomolecules has become standard practice in molecular
      biosciences. Modifications are used for detection, sorting and isolation of small
      molecules, complexes and entire cells. We have recently reported a method for
      introducing internal chemical and structural modifications into kbp-sized DNA
      target substrates that are frequently used in single-molecule experiments. It
      makes use of nicking enzymes that create single-stranded DNA gaps, which can be
      subsequently filled with labeled oligonucleotides. Here we provide a detailed
      protocol and further expand this method. We show that modifications can be
      introduced at distant loci within one molecule in a simple one-pot reaction. In
      addition, we achieve labeling on both strands at a specific locus, as
      demonstrated by Forster resonance energy transfer (FRET) experiments. The
      protocol requires an initial cloning of the target substrate (3-5 d), whereas the
      labeling itself takes 4-6 h. More elaborate purification and verification of
      label incorporation requires 2 h for each method.

PMID- 22402636
TI  - 4D solid-state NMR for protein structure determination.
AB  - Solid-state NMR offers the chance to extend structural studies to proteins that
      are otherwise difficult to study at atomic resolution, such as protein fibrils,
      membrane proteins or poorly diffracting crystals. As two-dimensional spatial
      correlation NMR spectra of proteins suffer from severe resonance overlap, we
      analyze in this perspective article the potential of higher-dimensional (3D and
      4D) proton-detected experiments, which have an increased number of identifiable
      and assignable distance restraints for solid-state structural studies. We discuss
      practical considerations for the NMR measurements and the preparation of suitable
      protein samples and show results of structure calculations from 4D solid-state
      NMR spectra.

PMID- 22402635
TI  - Second harmonic generation microscopy for quantitative analysis of collagen
      fibrillar structure.
AB  - Second-harmonic generation (SHG) microscopy has emerged as a powerful modality
      for imaging fibrillar collagen in a diverse range of tissues. Because of its
      underlying physical origin, it is highly sensitive to the collagen fibril/fiber
      structure, and, importantly, to changes that occur in diseases such as cancer,
      fibrosis and connective tissue disorders. We discuss how SHG can be used to
      obtain more structural information on the assembly of collagen in tissues than is
      possible by other microscopy techniques. We first provide an overview of the
      state of the art and the physical background of SHG microscopy, and then describe
      the optical modifications that need to be made to a laser-scanning microscope to
      enable the measurements. Crucial aspects for biomedical applications are the
      capabilities and limitations of the different experimental configurations. We
      estimate that the setup and calibration of the SHG instrument from its component
      parts will require 2-4 weeks, depending on the level of the user's experience.

PMID- 22402637
TI  - 9-Amino acridine pharmacokinetics, brain distribution, and in vitro/in vivo
      efficacy against malignant glioma.
AB  - PURPOSE: The delivery of drugs to the brain is a major obstacle in the design and
      development of useful treatments for malignant glioma. Previous studies by our
      laboratory have identified a series of 9-amino acridine compounds that block the
      catalytic cycle of topoisomerase II resulting in apoptosis and cell death in a
      variety of cancer cell lines. METHODS: This study reports the in vitro and in
      vivo activity of two promising lead compounds, [{9-[2-(1H-Indol-3-yl)-ethylamino]
      acridin-4-yl}-(4-methyl-piperazin-1-yl)-methanone (1) and [9-(1-Benzyl-piperidin
      4-ylamino)-acridin-3-yl]-(4-methyl-piperazin-1-yl)-methanone] (2), using an
      orthotopic glioblastoma mouse model. In addition, the absorption, distribution,
      and metabolism properties are characterized by determining metabolic stability,
      MDCK accumulation, Pgp efflux transport, plasma protein binding, and brain
      distribution in mouse pharmacokinetic studies. RESULTS: The efficacy results
      indicate low micromolar ED(50) values against glioma cells and a significant
      increase in the survival of glioma-bearing mice dosed with (2) (p < 0.05).
      Pharmacokinetic data collected at time intervals following a 60 mg/kg oral dose
      of acridine 1 and 2 showed both compounds penetrate the blood-brain barrier
      yielding peak concentrations of 0.25 MUM and 0.6 MUM, respectively. Peak plasma
      concentrations were determined to be 2.25 MUM (1) and 20.38 MUM (2). The results
      were further compared with data collected using a 15 mg/kg intravenous dose of 2
      which yielded a peak concentration in the brain of 1.7 MUM at 2.0 h relative to a
      2.04 MUM peak plasma concentration. The bioavailability was calculated to be
      83.8%. CONCLUSION: Taken overall, the results suggest compounds in this series
      may offer new strategies for the design of chemotherapeutics for treating brain
      cancers with high oral bioavailability and improved efficacy.

PMID- 22402638
TI  - The validity of upper-limb neurodynamic tests for detecting peripheral
      neuropathic pain.
AB  - SYNOPSIS: The validity of upper-limb neurodynamic tests (ULNTs) for detecting
      peripheral neuropathic pain (PNP) was assessed by reviewing the evidence on
      plausibility, the definition of a positive test, reliability, and concurrent
      validity. Evidence was identified by a structured search for peer-reviewed
      articles published in English before May 2011. The quality of concurrent validity
      studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies
      tool, where appropriate. Biomechanical and experimental pain data support the
      plausibility of ULNTs. Evidence suggests that a positive ULNT should at least
      partially reproduce the patient's symptoms and that structural differentiation
      should change these symptoms. Data indicate that this definition of a positive
      ULNT is reliable when used clinically. Limited evidence suggests that the median
      nerve test, but not the radial nerve test, helps determine whether a patient has
      cervical radiculopathy. The median nerve test does not help diagnose carpal
      tunnel syndrome. These findings should be interpreted cautiously, because
      diagnostic accuracy might have been distorted by the investigators' definitions
      of a positive ULNT. Furthermore, patients with PNP who presented with increased
      nerve mechanosensitivity rather than conduction loss might have been incorrectly
      classified by electrophysiological reference standards as not having PNP. The
      only evidence for concurrent validity of the ulnar nerve test was a case study on
      cubital tunnel syndrome. We recommend that researchers develop more comprehensive
      reference standards for PNP to accurately assess the concurrent validity of ULNTs
      and continue investigating the predictive validity of ULNTs for prognosis or
      treatment response.

PMID- 22402639
TI  - Do urodynamic parameters predict persistent postoperative stress incontinence
      after midurethral sling? A systematic review.
AB  - INTRODUCTION AND HYPOTHESIS: It is unclear whether preoperative urodynamic study
      (UDS) values are predictive of outcomes after midurethral sling. MATERIALS AND
      METHODS: We systematically reviewed multiple databases from January 1989 to
      October 2011 for English-language studies correlating UDS data with postoperative
      outcomes after midurethral slings. We performed random effects model meta
      analyses, as indicated. Relative risk (RR) ratios for the outcome of stress
      urinary incontinence (SUI) cure were calculated using high maximum urethral
      closure pressure (MUCP) and Valsalva leak point pressure (VLPP) values as the
      reference group. RESULTS: High preoperative MUCP was associated with cure after
      retropubic [RR 0.67; 95% confidence interval (CI) 0.47-0.97)] and transobturator
      slings (RR 0.65; 95% CI 0.49-0.90). High preoperative VLPP was also associated
      with cure after retropubic sling (RR 0.89; 95% CI 0.82-0.96), but this
      relationship did not achieve statistical significance for cure after
      transobturator sling (RR 0.86; 95% CI 0.74-1.00). CONCLUSIONS: Preoperative MUCP
      and VLPP values may add insight into postoperative outcomes after surgical
      treatment for SUI.

PMID- 22402640
TI  - High uterosacral ligament vaginal vault suspension: comparison of absorbable vs.
      permanent suture for apical fixation.
AB  - INTRODUCTION AND HYPOTHESIS: The primary objective of this study was to compare
      outcomes of absorbable and permanent suture for apical support with high
      uterosacral ligament vaginal vault suspension (HUSLS). The secondary objective
      was to investigate the rate of suture erosion. METHODS: This was a retrospective
      study of patients who underwent HUSLS with delayed absorbable and primarily
      permanent suture. Apical support was calculated as a new variable: Percent of
      Perfect Ratio (POP-R). This variable measures apical support as the position of
      the apex in relation to vaginal length. RESULTS: At 1-year follow-up, there was
      no significant difference in apical support between the two groups. The number of
      patients who suffered from suture erosion in the cohort that received permanent
      suture was 11 (22%). CONCLUSIONS: Permanent suture, in comparison with delayed
      absorbable suture, for HUSLS does not offer significantly better apical support
      at short-term follow-up. It is also associated with a high rate of suture
      erosion.

PMID- 22402641
TI  - Anterior and posterior compartment 3D endovaginal ultrasound anatomy based on
      direct histologic comparison.
AB  - INTRODUCTION AND HYPOTHESIS: We used direct histologic comparison to validate the
      use of 3D endovaginal ultrasound (EVUS) as a novel and emerging technology for
      evaluating the structures found in the anterior and posterior pelvic floor
      compartments. METHODS: A young nulliparous female pelvis specimen was dissected
      and histologic slides were prepared by making 8-Micron-thick sagittal cuts. The
      slides were stained with Mallory trichrome and arranged to form large sections
      encompassing each anterior and posterior sagittal plane. Healthy nulliparous
      women underwent 3D EVUS to obtain 3D cubes of the anterior and posterior
      compartments. Two investigators independently evaluated the anterior and
      posterior midsagittal structures. The investigators mutually viewed the images
      and calculated urethral and anal sphincter measurements. RESULTS: Thirty-one
      nulliparous women underwent 3D EVUS; 77% of the participants were Caucasian, with
      mean age 31.8 [standard deviation (SD) 5.8] and mean body mass index (BMI) of
      28.5 (SD 7.9). The following mean (SD) measurements were obtained: urethral
      length 36 mm (+/- 5); striated urogenital sphincter area 0.6 cm(2) (+/- 0.16);
      longitudinal and circular smooth muscle area 1.1 cm(2) (+/- 0.4); urethral
      complex width 14 mm (+/- 2); urethral complex area 1.3 cm(2) (+/- 0.4); internal
      anal sphincter length 26 mm (+/- 4); internal anal sphincter thickness 3.2 mm (+/
      0.8); and rectovaginal septum length 31 mm (+/- 5). The agreement for
      visualization of structures was as follows: vesical trigone 96% (kappa = 0.65),
      trigonal ring 94% (kappa = 0.8), trigonal plate 84% (kappa = 0.6); longitudinal
      and circular smooth muscle 100%; compressor urethra 97% (kappa = 0.85); striated
      urogenital sphincter 97% (kappa = 0.85); rectovaginal septum 100%; internal anal
      sphincter 100%; external anal sphincter subdivisions 100%. CONCLUSIONS: Three
      dimensional EVUS can be used to visualize structures of the anterior and
      posterior compartments in nullipara.

PMID- 22402642
TI  - Foreign body in the bladder 11 years after intravaginal pessary.
AB  - Vaginal pessaries used for symptomatic pelvic organ prolapse (POP) rarely develop
      complications when regularly monitored. However, many reports of complications of
      neglected pessaries have been described. Patients presenting with pessary
      complications report a variety of symptoms ranging from malodorous discharge or
      recurrent infections to more severe symptoms such as vaginal bleeding, complete
      urinary incontinence, or defecatory obstruction. Complete pessary encapsulation
      within the bladder is rare. We present the case of a 79-year-old postmenopausal
      woman referred to a tertiary care center for treatment of a large intravesical
      foreign body 11 years after pessary placement. The patient successfully underwent
      minimally invasive surgery to remove the foreign body and repair the bladder
      defect. Physicians should have a low threshold for diagnostic imaging in patients
      presenting with unclear history. Large intravesical foreign bodies can be removed
      by a vaginal approach with good outcomes.

PMID- 22402643
TI  - Colon and intestinal adaptation in children with short bowel syndrome.

PMID- 22402644
TI  - Adult nutrition assessment tutorial.
AB  - This tutorial presents a systematic approach to nutrition assessment based on a
      modern appreciation for the contributions of inflammation that serve as the
      foundation for newly proposed consensus definitions for malnutrition syndromes.
      Practical indicators of malnutrition and inflammation have been selected to guide
      diagnosis that include medical/surgical history and clinical diagnosis, clinical
      signs and physical examination, anthropometric data, laboratories, dietary
      assessment, and functional outcomes. Knowledge of systematic nutrition assessment
      and appropriate diagnosis of malnutrition will help to guide proper interventions
      and expected outcomes.

PMID- 22402645
TI  - Mycobacterium lepromatosis: emerging strain or species?

PMID- 22402647
TI  - Early risk factors for neonatal mortality in CAKUT: analysis of 524 affected
      newborns.
AB  - BACKGROUND: Congenital abnormalities of the kidney and urinary tract (CAKUT) are
      significant causes of morbidity. The aim of the study was to determine predictive
      factors of mortality in newborns with CAKUT. METHODS: All 29,653 consecutive
      newborns hospitalized in a tertiary neonatal unit between 1996 and 2006 were
      evaluated. The main outcome was neonatal mortality. The variables analyzed as
      risk factors were maternal age, first pregnancy, low birth weight (LBW),
      prematurity, oligohydramnios, and CAKUT associated with other malformations
      (Associated CAKUT). RESULTS: CAKUT was detected in 524 newborns, with an overall
      prevalence of 17.7 per 1,000 live births. A total of 325 (62%) cases were
      classified as urinary tract dilatation, 79 (15.1%) as renal cystic disease, and
      120 (22.9%) as other subgroups. In the urinary tract dilatation subgroup,
      independent risk factors for early mortality were Associated CAKUT [odds ratio
      (OR) 20.7], prematurity (OR 4.5) LBW (OR 3.8), oligohydramnios (OR 3.0), and
      renal involvement (OR 3.0). In the renal cystic disease subgroup, two variables
      remained associated with neonatal mortality: LBW (OR 12.3) and Associated CAKUT
      (OR 21.4). CONCLUSION: The presence of extrarenal anomalies was a strong
      predictor of poor outcome in a larger series of infants with CAKUT.

PMID- 22402648
TI  - Interactions between network synchrony and the dynamics of neuronal threshold.
AB  - Synchronous activity impacts on a range of functional brain capacities in health
      and disease. To address the interrelations between cellular level activity and
      network-wide synchronous events, we implemented in vitro a recently introduced
      technique, the response clamp, which enables online monitoring of single neuron
      threshold dynamics while ongoing network synchronous activity continues
      uninterrupted. We show that the occurrence of a synchronous network event causes
      a significant biphasic change in the single neuron threshold. These threshold
      dynamics are correlated across the neurons constituting the network and are
      entailed by the input to the neurons rather than by their own spiking (i.e.,
      output) activity. The magnitude of network activity during a synchronous event is
      correlated with the threshold state of individual neurons at the event's onset.
      Recovery from the impact of a given synchronous event on the neuronal threshold
      lasts several seconds and seems to be a key determinant of the time to the next
      spontaneously occurring synchronous event. Moreover, the neuronal threshold is
      shown to be correlated with the excitability dynamics of the entire network. We
      conclude that the relations between the two levels (network activity and the
      single neuron threshold) should be thought of in terms that emphasize their
      interactive nature.

PMID- 22402650
TI  - Microcircuits of excitatory and inhibitory neurons in layer 2/3 of mouse barrel
      cortex.
AB  - Synaptic interactions between nearby excitatory and inhibitory neurons in the
      neocortex are thought to play fundamental roles in sensory processing. Here, we
      have combined optogenetic stimulation, whole cell recordings, and computational
      modeling to define key functional microcircuits within layer 2/3 of mouse primary
      somatosensory barrel cortex. In vitro optogenetic stimulation of excitatory layer
      2/3 neurons expressing channelrhodopsin-2 evoked a rapid sequence of excitation
      followed by inhibition. Fast-spiking (FS) GABAergic neurons received large
      amplitude, fast-rising depolarizing postsynaptic potentials, often driving action
      potentials. In contrast, the same optogenetic stimulus evoked small-amplitude,
      subthreshold postsynaptic potentials in excitatory and non-fast-spiking (NFS)
      GABAergic neurons. To understand the synaptic mechanisms underlying this network
      activity, we investigated unitary synaptic connectivity through multiple
      simultaneous whole cell recordings. FS GABAergic neurons received unitary
      excitatory postsynaptic potentials with higher probability, larger amplitudes,
      and faster kinetics compared with NFS GABAergic neurons and other excitatory
      neurons. Both FS and NFS GABAergic neurons evoked robust inhibition on
      postsynaptic layer 2/3 neurons. A simple computational model based on the
      experimentally determined electrophysiological properties of the different
      classes of layer 2/3 neurons and their unitary synaptic connectivity accounted
      for key aspects of the network activity evoked by optogenetic stimulation,
      including the strong recruitment of FS GABAergic neurons acting to suppress
      firing of excitatory neurons. We conclude that FS GABAergic neurons play an
      important role in neocortical microcircuit function through their strong local
      synaptic connectivity, which might contribute to driving sparse coding in
      excitatory layer 2/3 neurons of mouse barrel cortex in vivo.

PMID- 22402649
TI  - Interaction between telencephalic signals and respiratory dynamics in songbirds.
AB  - The mechanisms by which telencephalic areas affect motor activities are largely
      unknown. They could either take over motor control from downstream motor circuits
      or interact with the intrinsic dynamics of these circuits. Both models have been
      proposed for telencephalic control of respiration during learned vocal behavior
      in birds. The interactive model postulates that simple signals from the
      telencephalic song control areas are sufficient to drive the nonlinear
      respiratory network into producing complex temporal sequences. We tested this
      basic assumption by electrically stimulating telencephalic song control areas and
      analyzing the resulting respiratory patterns in zebra finches and in canaries. We
      found strong evidence for interaction between the rhythm of stimulation and the
      intrinsic respiratory rhythm, including naturally emerging subharmonic behavior
      and integration of lateralized telencephalic input. The evidence for clear
      interaction in our experimental paradigm suggests that telencephalic vocal
      control also uses a similar mechanism. Furthermore, species differences in the
      response of the respiratory system to stimulation show parallels to differences
      in the respiratory patterns of song, suggesting that the interactive production
      of respiratory rhythms is manifested in species-specific specialization of the
      involved circuitry.

PMID- 22402652
TI  - A neuromechanical model explaining forward and backward stepping in the stick
      insect.
AB  - The mechanism underlying the generation of stepping has been the object of
      intensive studies. Stepping involves the coordinated movement of different leg
      joints and is, in the case of insects, produced by antagonistic muscle pairs. In
      the stick insect, the coordinated actions of three such antagonistic muscle pairs
      produce leg movements and determine the stepping pattern of the limb. The
      activity of the muscles is controlled by the nervous system as a whole and more
      specifically by local neuronal networks for each muscle pair. While many basic
      properties of these control mechanisms have been uncovered, some important
      details of their interactions in various physiological conditions have so far
      remained unknown. In this study, we present a neuromechanical model of the
      coupled protractor-retractor and levator-depressor neuromuscular systems and use
      it to elucidate details of their coordinated actions during forward and backward
      walking. The switch from protraction to retraction is evoked at a critical angle
      of the femur during downward movement. This angle represents a sensory input that
      integrates load, motion, and ground contact. Using the model, we can make
      detailed suggestions as to how rhythmic stepping might be generated by the
      central pattern generators of the local neuronal networks, how this activity
      might be transmitted to the corresponding motoneurons, and how the latter might
      control the activity of the related muscles. The entirety of these processes
      yields the coordinated interaction between neuronal and mechanical parts of the
      system. Moreover, we put forward a mechanism by which motoneuron activity could
      be modified by a premotor network and suggest that this mechanism might serve as
      a basis for fast adaptive behavior, like switches between forward and backward
      stepping, which occur, for example, during curve walking, and especially sharp
      turning, of insects.

PMID- 22402651
TI  - Fabrication of an inexpensive, implantable cooling device for reversible brain
      deactivation in animals ranging from rodents to primates.
AB  - We have developed a compact and lightweight microfluidic cooling device to
      reversibly deactivate one or more areas of the neocortex to examine its
      functional macrocircuitry as well as behavioral and cortical plasticity. The
      device, which we term the "cooling chip," consists of thin silicone tubing
      (through which chilled ethanol is circulated) embedded in mechanically compliant
      polydimethylsiloxane (PDMS). PDMS is tailored to compact device dimensions (as
      small as 21 mm(3)) that precisely accommodate the geometry of the targeted
      cortical area. The biocompatible design makes it suitable for both acute
      preparations and chronic implantation for long-term behavioral studies. The
      cooling chip accommodates an in-cortex microthermocouple measuring local cortical
      temperature. A microelectrode may be used to record simultaneous neural responses
      at the same location. Cortex temperature is controlled by computer regulation of
      the coolant flow, which can achieve a localized cortical temperature drop from 37
      to 20 degrees C in less than 3 min and maintain target temperature to within +/
      0.3 degrees C indefinitely. Here we describe cooling chip fabrication and
      performance in mediating cessation of neural signaling in acute preparations of
      rodents, ferrets, and primates.

PMID- 22402653
TI  - Encoding of reward expectation by monkey anterior insular neurons.
AB  - The insula, a cortical brain region that is known to encode information about
      autonomic, visceral, and olfactory functions, has recently been shown to encode
      information during reward-seeking tasks in both single neuronal recording and
      functional magnetic resonance imaging studies. To examine the reward-related
      activation, we recorded from 170 single neurons in anterior insula of 2 monkeys
      during a multitrial reward schedule task, where the monkeys had to complete a
      schedule of 1, 2, 3, or 4 trials to earn a reward. In one block of trials a
      visual cue indicated whether a reward would or would not be delivered in the
      current trial after the monkey successfully detected that a red spot turned
      green, and in other blocks the visual cue was random with respect to reward
      delivery. Over one-quarter of 131 responsive neurons were activated when the
      current trial would (certain or uncertain) be rewarded if performed correctly.
      These same neurons failed to respond in trials that were certain, as indicated by
      the cue, to be unrewarded. Another group of neurons responded when the reward was
      delivered, similar to results reported previously. The dynamics of population
      activity in anterior insula also showed strong signals related to knowing when a
      reward is coming. The most parsimonious explanation is that this activity codes
      for a type of expected outcome, where the expectation encompasses both certain
      and uncertain rewards.

PMID- 22402654
TI  - Tuning of gravity-dependent and gravity-independent vertical angular VOR gain
      changes by frequency of adaptation.
AB  - The gain of the vertical angular vestibulo-ocular reflex (aVOR) was adaptively
      increased and decreased in a side-down head orientation for 4 h in two cynomolgus
      monkeys. Adaptation was performed at 0.25, 1, 2, or 4 Hz. The gravity-dependent
      and -independent gain changes were determined over a range of head orientations
      from left-side-down to right-side-down at frequencies from 0.25 to 10 Hz, before
      and after adaptation. Gain changes vs. frequency data were fit with a Gaussian to
      determine the frequency at which the peak gain change occurred, as well as the
      tuning width. The frequency at which the peak gravity-dependent gain change
      occurred was approximately equal to the frequency of adaptation, and the width
      increased monotonically with increases in the frequency of adaptation. The
      gravity-independent component was tuned to the adaptive frequency of 0.25 Hz but
      was uniformly distributed over all frequencies when the adaptation frequency was
      1-4 Hz. The amplitude of the gravity-independent gain changes was larger after
      the aVOR gain decrease than after the gain increase across all tested
      frequencies. For the aVOR gain decrease, the phase lagged about 4 degrees  for
      frequencies below the adaptation frequency and led for frequencies above the
      adaptation frequency. For gain increases, the phase relationship as a function of
      frequency was inverted. This study demonstrates that the previously described
      dependence of aVOR gain adaptation on frequency is a property of the gravity
      dependent component of the aVOR only. The gravity-independent component of the
      aVOR had a substantial tuning curve only at an adaptation frequency of 0.25 Hz.

PMID- 22402655
TI  - Developmental constraints of quadrupedal coordination across crawling styles in
      human infants.
AB  - Human infants can crawl using several very different styles; this diversity
      appears at first glance to contradict our previous findings from hands-and-knees
      crawling, which suggested that there were strict limitations on coordination,
      imposed either mechanically or by the developing nervous system. To determine
      whether coordination was similarly restricted across crawling styles, we studied
      free crawling overground in 22 infants who used a number of different locomotor
      strategies. Despite the wide variety in the use of individual limbs and even the
      number of limbs used, the duration of the stance phase increased with duration of
      cycle, whereas the duration of the swing phase remained more constant.
      Additionally, all infants showed organized, rhythmic interlimb coordination.
      Alternating patterns (e.g., trotlike) predominated (86% of infants).
      Alternatively, yet much less frequently, all limbs used could work in synchrony
      (14% of infants). Pacelike patterns were never observed, even in infants that
      crawled with the belly remaining in contact with the ground so that stability was
      not a factor. To explore the robustness of the interlimb coordination, a
      perturbation that prolonged swing of the leg was imposed on 14 additional infants
      crawling on hands and knees overground or on the treadmill. The perturbation led
      to a resetting of the crawling pattern, but never to a change in the coordination
      of the limbs. The findings concur with those regarding other infant animals,
      together suggesting that the nervous system itself limits the coordination
      patterns available at a young age.

PMID- 22402656
TI  - Intramuscular ketorolac inhibits activation of rat peripheral NMDA receptors.
AB  - The nonsteroidal anti-inflammatory drug (NSAID) diclofenac has local anesthetic
      like and peripheral N-methyl-d-aspartate (NMDA) receptor antagonist
      characteristics when administered at higher concentrations to masticatory muscle.
      It is not known if the ability to inhibit NMDA receptors is unique to diclofenac
      or shared by other NSAIDs. This study was undertaken to determine whether
      intramuscular injection of ketorolac or naproxen at concentrations that do not
      induce local anesthetic-like effects could attenuate jaw-closer muscle nociceptor
      discharge in anesthetized Sprague-Dawley rats. It was found that ketorolac (5 mM)
      inhibited hypertonic saline-evoked nociceptor discharge, which suggests that at
      this concentration, ketorolac has local anesthetic-like properties. A lower
      concentration of ketorolac (0.5 mM), which did not affect hypertonic saline
      evoked discharge, did inhibit nociceptor discharge evoked by NMDA. In contrast,
      naproxen (5 mM) did not alter hypertonic saline- or NMDA-evoked nociceptor
      discharge. Subsequent experiments revealed that ketorolac (0.5 mM) had no effect
      on nociceptor discharge evoked by alphabeta-methylene ATP, 5-hydroxytryptamine,
      or AMPA. The inhibitory effect of ketorolac did not appear to be related to
      cyclooxygenase inhibition, because the concentration of prostaglandin E(2) in the
      masticatory muscles 10 min after injection of either NSAID was not significantly
      decreased. The present study indicates that in vivo, ketorolac, but not naproxen,
      can antagonize NMDA-evoked nociceptor discharge similarly to diclofenac. We
      speculate that structural similarities between ketorolac and diclofenac could
      account for the ability of these NSAIDs to inhibit NMDA-evoked nociceptor
      discharge. These properties may partly explain the analgesic effect of
      intramuscularly injected ketorolac in the clinic.

PMID- 22402657
TI  - Recruitment of motor units in two fascicles of the semispinalis cervicis muscle.
AB  - This study investigated the behavior of motor units in the semispinalis cervicis
      muscle. Intramuscular EMG recordings were obtained unilaterally at levels C2 and
      C5 in 15 healthy volunteers (8 men, 7 women) who performed isometric neck
      extensions at 5%, 10%, and 20% of the maximal force [maximum voluntary
      contraction (MVC)] for 2 min each and linearly increasing force contractions from
      0 to 30% MVC over 3 s. Individual motor unit action potentials were identified.
      The discharge rate and interspike interval variability of the motor units in the
      two locations did not differ. However, the recruitment threshold of motor units
      detected at C2 (n = 16, mean +/- SD: 10.3 +/- 6.0% MVC) was greater than that of
      motor units detected at C5 (n = 92, 6.9 +/- 4.3% MVC) (P < 0.01). A significant
      level of short-term synchronization was identified in 246 of 307 motor unit pairs
      when computed within one spinal level but only in 28 of 110 pairs of motor units
      between the two levels. The common input strength, which quantifies motor unit
      synchronization, was greater for pairs within one level (0.47 +/- 0.32) compared
      with pairs between levels (0.09 +/- 0.07) (P < 0.05). In a second experiment on
      eight healthy subjects, interference EMG was recorded from the same locations
      during a linearly increasing force contraction from 0 to 40% MVC and showed
      significantly greater EMG amplitude at C5 than at C2. In conclusion, synaptic
      input is distributed partly independently and nonuniformly to different fascicles
      of the semispinalis cervicis muscle.

PMID- 22402658
TI  - Reach endpoint errors do not vary with movement path of the proprioceptive
      target.
AB  - Previous research has shown that reach endpoints vary with the starting position
      of the reaching hand and the location of the reach target in space. We examined
      the effect of movement direction of a proprioceptive target-hand, immediately
      preceding a reach, on reach endpoints to that target. Participants reached to
      visual, proprioceptive (left target-hand), or visual-proprioceptive targets (left
      target-hand illuminated for 1 s prior to reach onset) with their right hand. Six
      sites served as starting and final target locations (35 target movement
      directions in total). Reach endpoints do not vary with the movement direction of
      the proprioceptive target, but instead appear to be anchored to some other
      reference (e.g., body). We also compared reach endpoints across the single and
      dual modality conditions. Overall, the pattern of reaches for visual
      proprioceptive targets resembled those for proprioceptive targets, while reach
      precision resembled those for the visual targets. We did not, however, find
      evidence for integration of vision and proprioception based on a maximum
      likelihood estimator in these tasks.

PMID- 22402659
TI  - Repetitive spinal electromagnetic stimulation opens a window of synaptic
      plasticity in damaged spinal cord: role of NMDA receptors.
AB  - As we reported previously, propagation of action potentials through surviving
      axons is impaired dramatically, resulting in reduced transmission to lumbar
      motoneurons after midthoracic lateral hemisection (HX) in rats. The aim of the
      present study was to evoke action potentials through the spared fibers using
      noninvasive electromagnetic stimulation (EMS) over intact T2 vertebrae in an
      attempt to activate synaptic inputs to lumbar motoneurons and thus to enhance
      plasticity of spinal neural circuits after HX. We found that EMS was able to
      activate synaptic inputs to lumbar motoneurons and motor-evoked potentials (MEP)
      in hindlimb muscles in adult anesthetized rats. Amplitude of MEP was attenuated
      in parallel with the decline of responses recorded from the motoneuron pool after
      HX. Repetitive EMS (50 min, 0.2 Hz) facilitated the amplitudes of responses
      elicited by electric stimulation of lateral white matter or dorsal corticospinal
      tracts in HX rats. Facilitation sustained for at least 1.5 h after termination of
      EMS. The N-methyl-d-aspartate (NMDA) receptor blocker MK-801, injected
      intraspinally close to the recording electrode prior to EMS, did not alter these
      responses but blocked the EMS-induced facilitation, suggesting that activation of
      NMDA receptors is required to initiate an EMS-evoked increase. When MK-801 was
      administered after EMS-induced facilitation was established, it induced
      depression of these elevated responses. Results suggest that repetitive EMS over
      intact vertebrae could be used as a therapeutic approach to open a window of
      synaptic plasticity after incomplete midthoracic injuries, i.e., to activate NMDA
      receptors in the lumbar motoneuron pool at synaptic inputs and to strengthen
      transmission in damaged spinal cord.

PMID- 22402660
TI  - Use of galvanic vestibular feedback to control postural orientation in
      decerebrate rabbits.
AB  - In quadrupeds, the dorsal-side-up body orientation during standing is maintained
      due to a postural system that is driven by feedback signals coming mainly from
      limb mechanoreceptors. In caudally decerebrated (postmammillary) rabbits, the
      efficacy of this system is considerably reduced. In this paper, we report that
      the efficacy of postural control in these animals can be restored with galvanic
      vestibular stimulation (GVS) applied transcutaneously to the labyrinths. In
      standing intact rabbits, GVS causes a lateral body sway towards the positive
      electrode. We used this GVS-caused sway to counteract the lateral body sway
      resulting from a mechanical perturbation of posture. Experiments were performed
      on postmammillary rabbits that stood on the tilting platform with their
      hindlimbs. To make the GVS value dependent on the postural perturbation (i.e., on
      the lateral body sway caused by tilt of the platform), an artificial feedback
      loop was formed in the following ways: 1) Information about the body sway was
      provided by a mechanical sensor; 2) The GVS current was applied when the sway
      exceeded a threshold value; the polarity of the current was determined by the
      sway direction. This simple algorithm allowed the "hybrid" postural system to
      maintain the dorsal-side-up orientation of the hindquarters when the platform was
      tilted by +/- 20 degrees . Thus, an important postural function, i.e., securing
      lateral stability during standing, can be restored in decerebrate rabbits with
      the GVS-based artificial feedback. We suggest that such a control system can
      compensate for the loss of lateral stability of various etiologies, and can be
      used for restoration of balance control in patients with impaired postural
      functions.

PMID- 22402662
TI  - Dynamics of spatial frequency tuning in mouse visual cortex.
AB  - Neuronal spatial frequency tuning in primary visual cortex (V1) substantially
      changes over time. In both primates and cats, a shift of the neuron's preferred
      spatial frequency has been observed from low frequencies early in the response to
      higher frequencies later in the response. In most cases, this shift is
      accompanied by a decreased tuning bandwidth. Recently, the mouse has gained
      attention as a suitable animal model to study the basic mechanisms of visual
      information processing, demonstrating similarities in basic neuronal response
      properties between rodents and highly visual mammals. Here we report the results
      of extracellular single-unit recordings in the anesthetized mouse where we
      analyzed the dynamics of spatial frequency tuning in V1 and the lateromedial area
      LM within the lateral extrastriate area V2L. We used a reverse-correlation
      technique to demonstrate that, as in monkeys and cats, the preferred spatial
      frequency of mouse V1 neurons shifted from low to higher frequencies later in the
      response. However, this was not correlated with a clear selectivity increase or
      enhanced suppression of responses to low spatial frequencies. These results
      suggest that the neuronal connections responsible for the temporal shift in
      spatial frequency tuning may considerably differ between mice and monkeys.

PMID- 22402661
TI  - Synapse maturation is enhanced in the binocular region of the retinocollicular
      map prior to eye opening.
AB  - In the developing visual system of mammals, retinal axons from the two eyes
      compete for postsynaptic partners. After eye opening, this process is regulated
      in part by homeostatically constrained competition for synaptic connectivity with
      target neurons. However, prior to eye opening, the functional and synaptic basis
      of binocular map development is unclear. To examine the role of binocular
      interactions during early stages of visual map development, we performed in vitro
      patch-clamp recordings from the superior colliculus (SC) of neonatal mice. Using
      newly designed slice preparations, we compared retinocollicular synapse
      development in the medial SC, which receives binocular input, and the lateral SC,
      which is predominantly monocular. Surprisingly, we found that at P6-7, when eye
      specific segregation has just emerged, retinocollicular synapses were stronger
      and more mature and dendritic arbors were more elaborate in the medial than the
      lateral SC. Furthermore, monocular enucleation of the ipsilateral eye at P0
      selectively reduced synaptic strength and dendritic branching in the medial SC
      and abolished the differences normally observed between the two slices at P6-7.
      This specifically implicates binocular interactions in the development of
      retinocollicular connectivity prior to eye opening. Our findings contrast with
      the predictions of a constrained-connectivity model of binocular map development
      and suggest instead that binocular competition prior to eye opening enhances
      retinocollicular synaptic strength and the morphological development of retino
      recipient neurons.

PMID- 22402663
TI  - Lysine methylation of FOXO3 regulates oxidative stress-induced neuronal cell
      death.
AB  - FOXO transcription factors have a critical role in oxidative stress-induced
      neuronal cell death. A variety of post-translational modifications of FOXO family
      proteins have been reported, including phosphorylation, acetylation,
      ubiqutination and recently arginine methylation. Here, we demonstrate that the
      methyltransferase Set9 methylates FOXO3 at lysine 270. Methylation of FOXO3 leads
      to the inhibition of its DNA-binding activity and transactivation. Accordingly,
      lysine methylation reduces oxidative stress-induced and FOXO3-mediated Bim
      expression and neuronal apoptosis in neurons. Collectively, these findings define
      a novel modification of FOXO3 and show that lysine methylation negatively
      regulates FOXO3-mediated transcription and neuronal apoptosis.

PMID- 22402664
TI  - Eomesodermin induces Mesp1 expression and cardiac differentiation from embryonic
      stem cells in the absence of Activin.
AB  - The transcription factor Eomesodermin (Eomes) is involved in early embryonic
      patterning, but the range of cell fates that it controls as well as its
      mechanisms of action remain unclear. Here we show that transient expression of
      Eomes promotes cardiovascular fate during embryonic stem cell differentiation.
      Eomes also rapidly induces the expression of Mesp1, a key regulator of
      cardiovascular differentiation, and directly binds to regulatory sequences of
      Mesp1. Eomes effects are strikingly modulated by Activin signalling: high levels
      of Activin inhibit the promotion of cardiac mesoderm by Eomes, while they enhance
      Eomes-dependent endodermal specification. These results place Eomes upstream of
      the Mesp1-dependent programme of cardiogenesis, and at the intersection of
      mesodermal and endodermal specification, depending on the levels of Activin/Nodal
      signalling.

PMID- 22402665
TI  - Science in Suzhou: establishment and function of neural circuits.
AB  - The Cold Spring Harbour Asia conference on 'Assembly, Plasticity, Dysfunction and
      Repair of Neural Circuits' took place in Suzhou, China, in October 2011.
      Developmental, cell, molecular and systems neuroscientists convened to discuss
      the establishment, function and plasticity of neural circuits in diverse
      organisms.

PMID- 22402667
TI  - Predicting drug targets based on protein domains.
AB  - The identification of interactions between drugs and proteins plays key roles in
      understanding mechanisms underlying drug actions and can lead to new drug design
      strategies. Here, we present a novel statistical approach, namely PDTD
      (Predicting Drug Targets with Domains), to predict potential target proteins of
      new drugs based on derived interactions between drugs and protein domains. The
      known target proteins of those drugs that have similar therapeutic effects allow
      us to infer interactions between drugs and protein domains which in turn leads to
      identification of potential drug-protein interactions. Benchmarking with known
      drug-protein interactions shows that our proposed methodology outperforms
      previous methods that exploit either protein sequences or compound structures to
      predict drug targets, which demonstrates the predictive power of our proposed
      PDTD method.

PMID- 22402668
TI  - Tracking energy transfer from excited to accepting modes: application to water
      bend vibrational relaxation.
AB  - We extend, via a reformulation in terms of Poisson brackets, the method developed
      previously (Rey et al., J. Phys. Chem. A, 2009, 113, 8949) allowing analysis of
      the pathways of an excited molecule's ultrafast vibrational relaxation in terms
      of intramolecular and intermolecular contributions. In particular we show how to
      ascertain, through the computation of power and work, which portion of an initial
      excess molecular energy (e.g. vibrational) is transferred to various degrees of
      freedom (e.g. rotational, translational) of the excited molecule itself and its
      neighbors. The particular case of bend excess energy relaxation in pure water is
      treated in detail, completing the picture reported in the work cited above. It is
      shown explicitly, within a classical description, that almost all of the initial
      water bend excitation energy is transferred-either indirectly, via Fermi
      resonance centrifugal coupling to the bend-excited water's rotation, or directly
      via intermolecular coupling- to local water librations, only involving molecules
      in the first two hydration shells of the vibrationally excited water molecule.
      Finally, it is pointed out that the Poisson bracket formulation can also be
      applied to elucidate the microscopic character of solvation and rotational
      dynamics, and should prove useful in developing a quantum treatment for energy
      flow in condensed phases.

PMID- 22402666
TI  - Non-apoptotic functions of apoptosis-regulatory proteins.
AB  - During the past two decades, apoptotic cell death has been the subject of an
      intense wave of investigation, leading to the discovery of multiple gene products
      that govern both its induction and execution. In parallel, it has progressively
      become evident that most, if not all, proteins that had initially been discovered
      for their essential role in apoptosis also mediate a wide range of non-apoptotic
      functions. On the one hand, apoptotic regulators and executioners are involved in
      non-lethal physiological processes as diverse as cell cycle progression,
      differentiation, metabolism, autophagy and inflammation. On the other hand, pro
      apoptotic proteins can control other modalities of programmed cell death, in
      particular regulated necrosis. In this review, we summarize the unconventional
      roles of the apoptotic core machinery from a functional perspective and discuss
      their pathophysiological implications.

PMID- 22402669
TI  - Innate immunity: Linking mitochondria and microbes to inflammasomes.

PMID- 22402671
TI  - Gene regulation: Clocking on for TLR9.

PMID- 22402672
TI  - T cell development: Tonsils turn out T cells too.

PMID- 22402670
TI  - Regulating the adaptive immune response to respiratory virus infection.
AB  - Recent years have seen several advances in our understanding of immunity to virus
      infection of the lower respiratory tract, including to influenza virus infection.
      Here, we review the cellular targets of viruses and the features of the host
      immune response that are unique to the lungs. We describe the interplay between
      innate and adaptive immune cells in the induction, expression and control of
      antiviral immunity, and discuss the impact of the infected lung milieu on
      moulding the response of antiviral effector T cells. Recent findings on the
      mechanisms that underlie the increased frequency of severe pulmonary bacterial
      infections following respiratory virus infection are also discussed.

PMID- 22402673
TI  - Effect of oral monthly ibandronate on bone microarchitecture in women with
      osteopenia-a randomized placebo-controlled trial.
AB  - We have examined the effect of oral monthly ibandronate on distal radius and
      tibia microarchitecture with high-resolution peripheral quantitative tomography
      compared with placebo, in women with osteopenia, and found that ibandronate did
      not significantly affect trabecular bone but improved cortical density and
      thickness at the tibia. METHODS: We have examined the effect of ibandronate on
      bone microarchitecture with peripheral high-resolution quantitative computed
      tomography (HR-pQCT) in a randomized placebo-controlled trial among 148 women
      with osteopenia. Patients received either oral 150 mg monthly ibandronate or
      placebo over 24 months. Bone microarchitecture was assessed at baseline, 6, 12,
      and 24 months, using HR-pQCT at the distal radius and tibia; areal bone mineral
      density (aBMD) was measured with DXA at the spine, hip, and radius. RESULTS: At
      12 months, there was no significant difference in trabecular bone volume at the
      radius (the primary end point) between women on ibandronate (10.8 +/- 2.5%) and
      placebo (10.5 +/- 2.9%), p = 0.25. There was no significant difference in other
      radius trabecular and cortical microarchitecture parameters at 12 and 24 months.
      In contrast, at the tibia, cortical vBMD in the ibandronate group was
      significantly greater than in the placebo group at 6, 12, and 24 months, with
      better cortical thickness at 6, 12, and 24 months. With ibandronate, aBMD was
      significantly increased at the hip and spine at 12 and 24 months but at the
      radius was significantly superior to placebo only at 24 months. Most of the
      adverse events related to ibandronate were expected with bisphosphonate use, and
      none of them were serious. CONCLUSION: We conclude that 12 months of treatment
      with ibandronate in women with osteopenia did not affect trabecular bone
      microarchitecture, but improved cortical vBMD at the tibia at 12 and 24 months,
      and preserved cortical thickness at the tibia.

PMID- 22402674
TI  - Expression of endothelial nitric oxide synthase protein is not necessary for
      mechanical strain-induced nitric oxide production by cultured osteoblasts.
AB  - Regulation of nitric oxide (NO) production is considered essential in mechanical
      load-related osteogenesis. We examined whether osteoblast endothelial NO synthase
      (eNOS)-derived NO production was regulated by HSP90. We found that HSP90 is
      essential for strain-related NO release but appears to be independent of eNOS in
      cultured osteoblasts. INTRODUCTION: NO is a key regulator of bone mass, and its
      production by bone cells is regarded as essential in mechanical strain-related
      osteogenesis. We sought to identify whether bone cell NO production relied upon
      eNOS, considered to be the predominant NOS isoform in bone, and whether this was
      regulated by an HSP90-dependent mechanism. METHODS: Using primary rat long bone
      derived osteoblasts, the ROS 17/2.8 cell line and primary mouse osteoblasts,
      derived from wild-type and eNOS-deficient (eNOS(-/-)) mice, we examined by
      immunoblotting the expression of eNOS using a range of well-characterised
      antibodies and extraction methods, measured NOS activity by monitoring the
      conversion of radiolabelled L-arginine to citrulline and examined the production
      of NO by bone cells subjected to mechanical strain application under various
      conditions. RESULTS: Our studies have revealed that eNOS protein and activity
      were both undetectable in osteoblast-like cells, that mechanical strain-induced
      NO production was retained in bone cells from eNOS-deficient mice, but that this
      strain-related induction of NO production was, however, dependent upon HSP90.
      CONCLUSIONS: Together, our studies indicate that HSP90 activity is essential for
      strain-related NO release by cultured osteoblasts and that this is highly likely
      to be achieved by an eNOS-independent mechanism.

PMID- 22402675
TI  - Uranyl adsorption on solvated edge surfaces of pyrophyllite: a DFT model study.
AB  - In a computational study we addressed the adsorption of uranyl UO(2)(2+) on
      solvated (110) and (010) edge surfaces of pyrophyllite, applying a density
      functional approach to periodic slab models. We explored bidentate adsorption
      complexes on various partially deprotonated adsorption sites: octahedral
      Al(O,OH), tetrahedral Si(O,OH), and mixed AlO-SiO. Aluminol sites were determined
      to be most favorable on the (110) surface of pyrophyllite, while on the (010)
      surface mixed AlO-SiO sites are preferred. The structural parameters of all low
      energy complexes on both surfaces agree rather well with EXAFS results for the
      structurally similar mineral montmorillonite. We calculate the average U-O
      distance to surface and aqua ligand oxygen atoms to increase with the increasing
      coordination number of uranyl whereas EXAFS results indicate the opposite trend.
      According to our results, several adsorption species, with different coordination
      numbers on different edge faces, may coexist on clay minerals. This computational
      finding rationalizes why earlier spectroscopic studies indicated the existence of
      more than one adsorption species, whereas a single type of adsorption complex was
      suggested from most EXAFS results.

PMID- 22402677
TI  - Comparison of reliability and responsiveness of patient-reported clinical outcome
      measures in knee osteoarthritis rehabilitation.
AB  - STUDY DESIGN: Secondary analysis, pretreatment-posttreatment observational study.
      OBJECTIVE: To compare the reliability and responsiveness of the Western Ontario
      and McMaster Universities Osteoarthritis Index (WOMAC), the Knee Outcome Survey
      activities of daily living subscale (KOS-ADL), and the Lower Extremity Functional
      Scale (LEFS) in individuals with knee osteoarthritis (OA). BACKGROUND: The WOMAC
      is the current standard in patient-reported measures of function in patients with
      knee OA. The KOS-ADL and LEFS were designed for potential use in patients with
      knee OA. If the KOS-ADL and LEFS are to be considered viable alternatives to the
      WOMAC for measuring patient-reported function in individuals with knee OA, they
      should have measurement properties comparable to the WOMAC. It would also be
      important to determine whether either of these instruments may be superior to the
      WOMAC in terms of reliability or responsiveness in this population. METHODS: Data
      from 168 subjects with knee OA, who participated in a rehabilitation program,
      were used in the analyses. Reliability and responsiveness of each outcome measure
      were estimated at follow-ups of 2, 6, and 12 months. Reliability was estimated by
      calculating the intraclass correlation coefficient (ICC2,1) for subjects who were
      unchanged in status from baseline at each follow-up time, based on a global
      rating of change score. To examine responsiveness, the standard error of the
      measurement, minimal detectable change, minimal clinically important difference,
      and the Guyatt responsiveness index were calculated for each outcome measure at
      each follow-up time. RESULTS: All 3 outcome measures demonstrated reasonable
      reliability and responsiveness to change. Reliability and responsiveness tended
      to decrease somewhat with increasing follow-up time. There were no substantial
      differences between outcome measures for reliability or any of the 3 measures of
      responsiveness at any follow-up time. CONCLUSION: The results do not indicate
      that one outcome measure is more reliable or responsive than another when applied
      to subjects with knee OA. We believe that all 3 instruments are appropriate
      outcome measures to examine change in functional status of patients with knee OA.

PMID- 22402679
TI  - On delay adjustment for dynamic load balancing in distributed virtual
      environments.
AB  - Distributed virtual environments (DVEs) are becoming very popular in recent
      years, due to the rapid growing of applications, such as massive multiplayer
      online games (MMOGs). As the number of concurrent users increases, scalability
      becomes one of the major challenges in designing an interactive DVE system. One
      solution to address this scalability problem is to adopt a multi-server
      architecture. While some methods focus on the quality of partitioning the load
      among the servers, others focus on the efficiency of the partitioning process
      itself. However, all these methods neglect the effect of network delay among the
      servers on the accuracy of the load balancing solutions. As we show in this
      paper, the change in the load of the servers due to network delay would affect
      the performance of the load balancing algorithm. In this work, we conduct a
      formal analysis of this problem and discuss two efficient delay adjustment
      schemes to address the problem. Our experimental results show that our proposed
      schemes can significantly improve the performance of the load balancing algorithm
      with neglectable computation overhead.

PMID- 22402678
TI  - Effects of the N-terminal and C-terminal domains of Meiothermus ruber CBS-01
      trehalose synthase on thermostability and activity.
AB  - Numerous trehalose synthases (TreS) from thermophilic microorganisms have extra C
      terminal domains. To determine the function of the N- and C-terminal domains of
      TreS from the thermophilic bacterium Meiothermus ruber CBS-01, the two domains
      were expressed. From the findings, the N-terminal domain from M. ruber was not
      active when compared with that from Thermus thermophilus, which had been studied
      previously. The circular dichroism spectrum showed that the secondary structure
      of N-terminal domain from M. ruber underwent a greater change than that of C
      terminus. In addition, the N-terminal domain from T. thermophilus and C terminus
      from M. ruber were fused. The fusion protein TSTtMr was more efficient and
      thermostable than the TreS from M. ruber. The N-terminal domain from M. ruber and
      C terminus from T. thermophilus were fused. The optimum temperature and
      thermostability of fusion protein TSMrTt were similar to the TreS from M. ruber.
      It was presumed that aside from the C-terminal domain, the N-terminal domain of
      TreS from thermophilic bacteria could influence thermostability. For the TreS
      from M. ruber, the mutant protein R392F led to a complete loss in activity, and
      R392A showed a sharp decrease in activity.

PMID- 22402680
TI  - Redirecting walking and driving for natural navigation in immersive virtual
      environments.
AB  - Walking is the most natural form of locomotion for humans, and real walking
      interfaces have demonstrated their benefits for several navigation tasks. With
      recently proposed redirection techniques it becomes possible to overcome space
      limitations as imposed by tracking sensors or laboratory setups, and,
      theoretically, it is now possible to walk through arbitrarily large virtual
      environments. However, walking as sole locomotion technique has drawbacks, in
      particular, for long distances, such that even in the real world we tend to
      support walking with passive or active transportation for longer-distance travel.
      In this article we show that concepts from the field of redirected walking can be
      applied to movements with transportation devices. We conducted psychophysical
      experiments to determine perceptual detection thresholds for redirected driving,
      and set these in relation to results from redirected walking. We show that
      redirected walking-and-driving approaches can easily be realized in immersive
      virtual reality laboratories, e. g., with electric wheelchairs, and show that
      such systems can combine advantages of real walking in confined spaces with
      benefits of using vehicle-based self-motion for longer-distance travel.

PMID- 22402681
TI  - Walking in a cube: novel metaphors for safely navigating large virtual
      environments in restricted real workspaces.
AB  - Immersive spaces such as 4-sided displays with stereo viewing and high-quality
      tracking provide a very engaging and realistic virtual experience. However,
      walking is inherently limited by the restricted physical space, both due to the
      screens (limited translation) and the missing back screen (limited rotation). In
      this paper, we propose three novel locomotion techniques that have three
      concurrent goals: keep the user safe from reaching the translational and
      rotational boundaries; increase the amount of real walking and finally, provide a
      more enjoyable and ecological interaction paradigm compared to traditional
      controller-based approaches. We notably introduce the "Virtual Companion", which
      uses a small bird to guide the user through VEs larger than the physical space.
      We evaluate the three new techniques through a user study with travel-to-target
      and path following tasks. The study provides insight into the relative strengths
      of each new technique for the three aforementioned goals. Specifically, if speed
      and accuracy are paramount, traditional controller interfaces augmented with our
      novel warning techniques may be more appropriate; if physical walking is more
      important, two of our paradigms (extended Magic Barrier Tape and Constrained
      Wand) should be preferred; last, fun and ecological criteria would favor the
      Virtual Companion.

PMID- 22402682
TI  - Impossible spaces: maximizing natural walking in virtual environments with self
      overlapping architecture.
AB  - Walking is only possible within immersive virtual environments that fit inside
      the boundaries of the user's physical workspace. To reduce the severity of the
      restrictions imposed by limited physical area, we introduce "impossible spaces,"
      a new design mechanic for virtual environments that wish to maximize the size of
      the virtual environment that can be explored with natural locomotion. Such
      environments make use of self-overlapping architectural layouts, effectively
      compressing comparatively large interior environments into smaller physical
      areas. We conducted two formal user studies to explore the perception and
      experience of impossible spaces. In the first experiment, we showed that
      reasonably small virtual rooms may overlap by as much as 56% before users begin
      to detect that they are in an impossible space, and that the larger virtual rooms
      that expanded to maximally fill our available 9.14 m x 9.14 m workspace may
      overlap by up to 31%. Our results also demonstrate that users perceive distances
      to objects in adjacent overlapping rooms as if the overall space was
      uncompressed, even at overlap levels that were overtly noticeable. In our second
      experiment, we combined several well-known redirection techniques to string
      together a chain of impossible spaces in an expansive outdoor scene. We then
      conducted an exploratory analysis of users' verbal feedback during exploration,
      which indicated that impossible spaces provide an even more powerful illusion
      when users are naive to the manipulation.

PMID- 22402683
TI  - Extended overview techniques for outdoor augmented reality.
AB  - In this paper, we explore techniques that aim to improve site understanding for
      outdoor Augmented Reality (AR) applications. While the first person perspective
      in AR is a direct way of filtering and zooming on a portion of the data set, it
      severely narrows overview of the situation, particularly over large areas. We
      present two interactive techniques to overcome this problem: multi-view AR and
      variable perspective view. We describe in details the conceptual, visualization
      and interaction aspects of these techniques and their evaluation through a
      comparative user study. The results we have obtained strengthen the validity of
      our approach and the applicability of our methods to a large range of application
      domains.

PMID- 22402684
TI  - Online tracking of outdoor lighting variations for augmented reality with moving
      cameras.
AB  - In augmented reality, one of key tasks to achieve a convincing visual appearance
      consistency between virtual objects and video scenes is to have a coherent
      illumination along the whole sequence. As outdoor illumination is largely
      dependent on the weather, the lighting condition may change from frame to frame.
      In this paper, we propose a full image-based approach for online tracking of
      outdoor illumination variations from videos captured with moving cameras. Our key
      idea is to estimate the relative intensities of sunlight and skylight via a
      sparse set of planar feature-points extracted from each frame. To address the
      inevitable feature misalignments, a set of constraints are introduced to select
      the most reliable ones. Exploiting the spatial and temporal coherence of
      illumination, the relative intensities of sunlight and skylight are finally
      estimated by using an optimization process. We validate our technique on a set of
      real-life videos and show that the results with our estimations are visually
      coherent along the video sequences.

PMID- 22402685
TI  - The right view from the wrong location: depth perception in stereoscopic multi
      user virtual environments.
AB  - Stereoscopic depth cues improve depth perception and increase immersion within
      virtual environments (VEs). However, improper display of these cues can distort
      perceived distances and directions. Consider a multi-user VE, where all users
      view identical stereoscopic images regardless of physical location. In this
      scenario, cues are typically customized for one "leader" equipped with a head
      tracking device. This user stands at the center of projection (CoP) and all other
      users ("followers") view the scene from other locations and receive improper
      depth cues. This paper examines perceived depth distortion when viewing
      stereoscopic VEs from follower perspectives and the impact of these distortions
      on collaborative spatial judgments. Pairs of participants made collaborative
      depth judgments of virtual shapes viewed from the CoP or after displacement
      forward or backward. Forward and backward displacement caused perceived depth
      compression and expansion, respectively, with greater compression than expansion.
      Furthermore, distortion was less than predicted by a ray-intersection model of
      stereo geometry. Collaboration times were significantly longer when participants
      stood at different locations compared to the same location, and increased with
      greater perceived depth discrepancy between the two viewing locations. These
      findings advance our understanding of spatial distortions in multi-user VEs, and
      suggest a strategy for reducing distortion.

PMID- 22402686
TI  - Geometric calibration of head-mounted displays and its effects on distance
      estimation.
AB  - Head-mounted displays (HMDs) allow users to observe virtual environments (VEs)
      from an egocentric perspective. However, several experiments have provided
      evidence that egocentric distances are perceived as compressed in VEs relative to
      the real world. Recent experiments suggest that the virtual view frustum set for
      rendering the VE has an essential impact on the user's estimation of distances.
      In this article we analyze if distance estimation can be improved by calibrating
      the view frustum for a given HMD and user. Unfortunately, in an immersive virtual
      reality (VR) environment, a full per user calibration is not trivial and manual
      per user adjustment often leads to mini- or magnification of the scene.
      Therefore, we propose a novel per user calibration approach with optical see
      through displays commonly used in augmented reality (AR). This calibration takes
      advantage of a geometric scheme based on 2D point - 3D line correspondences,
      which can be used intuitively by inexperienced users and requires less than a
      minute to complete. The required user interaction is based on taking aim at a
      distant target marker with a close marker, which ensures non-planar measurements
      covering a large area of the interaction space while also reducing the number of
      required measurements to five. We found the tendency that a calibrated view
      frustum reduced the average distance underestimation of users in an immersive VR
      environment, but even the correctly calibrated view frustum could not entirely
      compensate for the distance underestimation effects.

PMID- 22402687
TI  - Effects of immersion on visual analysis of volume data.
AB  - Volume visualization has been widely used for decades for analyzing datasets
      ranging from 3D medical images to seismic data to paleontological data. Many have
      proposed using immersive virtual reality (VR) systems to view volume
      visualizations, and there is anecdotal evidence of the benefits of VR for this
      purpose. However, there has been very little empirical research exploring the
      effects of higher levels of immersion for volume visualization, and it is not
      known how various components of immersion influence the effectiveness of
      visualization in VR. We conducted a controlled experiment in which we studied the
      independent and combined effects of three components of immersion (head tracking,
      field of regard, and stereoscopic rendering) on the effectiveness of
      visualization tasks with two x-ray microscopic computed tomography datasets. We
      report significant benefits of analyzing volume data in an environment involving
      those components of immersion. We find that the benefits do not necessarily
      require all three components simultaneously, and that the components have
      variable influence on different task categories. The results of our study improve
      our understanding of the effects of immersion on perceived and actual task
      performance, and provide guidance on the choice of display systems to designers
      seeking to maximize the effectiveness of volume visualization applications.

PMID- 22402688
TI  - Effective replays and summarization of virtual experiences.
AB  - Direct replay of the experience of a user in a virtual environment is difficult
      for others to watch due to unnatural camera motions. We present methods for
      replaying and summarizing these egocentric experiences that effectively
      communicate the user's observations while reducing unwanted camera movements. Our
      approach summarizes the viewpoint path as a concise sequence of viewpoints that
      cover the same parts of the scene. The core of our approach is a novel content
      dependent metric that can be used to identify similarities between viewpoints.
      This enables viewpoints to be grouped by similar contextual view information and
      provides a means to generate novel viewpoints that can encapsulate a series of
      views. These resulting encapsulated viewpoints are used to synthesize new camera
      paths that convey the content of the original viewer's experience. Projecting the
      initial movement of the user back on the scene can be used to convey the details
      of their observations, and the extracted viewpoints can serve as bookmarks for
      control or analysis. Finally we present performance analysis along with two forms
      of validation to test whether the extracted viewpoints are representative of the
      viewer's original observations and to test for the overall effectiveness of the
      presented replay methods.

PMID- 22402689
TI  - Haptic palpation for medical simulation in virtual environments.
AB  - Palpation is a physical examination technique where objects, e.g., organs or body
      parts, are touched with fingers to determine their size, shape, consistency and
      location. Many medical procedures utilize palpation as a supplementary
      interaction technique and it can be therefore considered as an essential basic
      method. However, palpation is mostly neglected in medical training simulators,
      with the exception of very specialized simulators that solely focus on palpation,
      e.g., for manual cancer detection. In this article we propose a novel approach to
      enable haptic palpation interaction for virtual reality-based medical simulators.
      The main contribution is an extensive user study conducted with a large group of
      medical experts. To provide a plausible simulation framework for this user study,
      we contribute a novel and detailed interaction algorithm for palpation with
      tissue dragging, which utilizes a multi-object force algorithm to support
      multiple layers of anatomy and a pulse force algorithm for simulation of an
      arterial pulse. Furthermore, we propose a modification for an off-the-shelf
      haptic device by adding a lightweight palpation pad to support a more realistic
      finger grip configuration for palpation tasks. The user study itself has been
      conducted on a medical training simulator prototype with a specific procedure
      from regional anesthesia, which strongly depends on palpation. The prototype
      utilizes a co-rotational finite-element approach for soft tissue simulation and
      provides bimanual interaction by combining the aforementioned techniques with
      needle insertion for the other hand. The results of the user study suggest
      reasonable face validity of the simulator prototype and in particular validate
      medical plausibility of the proposed palpation interaction algorithm.

PMID- 22402690
TI  - Evaluating display fidelity and interaction fidelity in a virtual reality game.
AB  - In recent years, consumers have witnessed a technological revolution that has
      delivered more-realistic experiences in their own homes through high-definition,
      stereoscopic televisions and natural, gesture-based video game consoles. Although
      these experiences are more realistic, offering higher levels of fidelity, it is
      not clear how the increased display and interaction aspects of fidelity impact
      the user experience. Since immersive virtual reality (VR) allows us to achieve
      very high levels of fidelity, we designed and conducted a study that used a six
      sided CAVE to evaluate display fidelity and interaction fidelity independently,
      at extremely high and low levels, for a VR first-person shooter (FPS) game. Our
      goal was to gain a better understanding of the effects of fidelity on the user in
      a complex, performance-intensive context. The results of our study indicate that
      both display and interaction fidelity significantly affect strategy and
      performance, as well as subjective judgments of presence, engagement, and
      usability. In particular, performance results were strongly in favor of two
      conditions: low-display, low-interaction fidelity (representative of traditional
      FPS games) and high-display, high-interaction fidelity (similar to the real
      world).

PMID- 22402691
TI  - Dense and dynamic 3D selection for game-based virtual environments.
AB  - 3D object selection is more demanding when, 1) objects densly surround the target
      object, 2) the target object is significantly occluded, and 3) when the target
      object is dynamically changing location. Most 3D selection techniques and
      guidelines were developed and tested on static or mostly sparse environments. In
      contrast, games tend to incorporate densly packed and dynamic objects as part of
      their typical interaction. With the increasing popularity of 3D selection in
      games using hand gestures or motion controllers, our current understanding of 3D
      selection needs revision. We present a study that compared four different
      selection techniques under five different scenarios based on varying object
      density and motion dynamics. We utilized two existing techniques, Raycasting and
      SQUAD, and developed two variations of them, Zoom and Expand, using iterative
      design. Our results indicate that while Raycasting and SQUAD both have weaknesses
      in terms of speed and accuracy in dense and dynamic environments, by making small
      modifications to them (i.e., flavoring), we can achieve significant performance
      increases.

PMID- 22402692
TI  - Scanning 3D full human bodies using Kinects.
AB  - Depth camera such as Microsoft Kinect, is much cheaper than conventional 3D
      scanning devices, and thus it can be acquired for everyday users easily. However,
      the depth data captured by Kinect over a certain distance is of extreme low
      quality. In this paper, we present a novel scanning system for capturing 3D full
      human body models by using multiple Kinects. To avoid the interference phenomena,
      we use two Kinects to capture the upper part and lower part of a human body
      respectively without overlapping region. A third Kinect is used to capture the
      middle part of the human body from the opposite direction. We propose a practical
      approach for registering the various body parts of different views under non
      rigid deformation. First, a rough mesh template is constructed and used to deform
      successive frames pairwisely. Second, global alignment is performed to distribute
      errors in the deformation space, which can solve the loop closure problem
      efficiently. Misalignment caused by complex occlusion can also be handled
      reasonably by our global alignment algorithm. The experimental results have shown
      the efficiency and applicability of our system. Our system obtains impressive
      results in a few minutes with low price devices, thus is practically useful for
      generating personalized avatars for everyday users. Our system has been used for
      3D human animation and virtual try on, and can further facilitate a range of
      home&#8211;oriented virtual reality (VR) applications.

PMID- 22402693
TI  - Interactive 3D model acquisition and tracking of building block structures.
AB  - We present a prototype system for interactive construction and modification of 3D
      physical models using building blocks. Our system uses a depth sensing camera and
      a novel algorithm for acquiring and tracking the physical models. The algorithm,
      Lattice-First, is based on the fact that building block structures can be
      arranged in a 3D point lattice where the smallest block unit is a basis in which
      to derive all the pieces of the model. The algorithm also makes it possible for
      users to interact naturally with the physical model as it is acquired, using
      their bare hands to add and remove pieces. We present the details of our
      algorithm, along with examples of the models we can acquire using the interactive
      system. We also show the results of an experiment where participants modify a
      block structure in the absence of visual feedback. Finally, we discuss two proof
      of-concept applications: a collaborative guided assembly system where one user is
      interactively guided to build a structure based on another user's design, and a
      game where the player must build a structure that matches an on-screen
      silhouette.

PMID- 22402694
TI  - Future of immunotherapy drug combinations and biomarkers.

PMID- 22402695
TI  - A simple indicator to rapidly assess the short-term impact of heat waves on
      mortality within the French heat warning system.
AB  - We propose a simple method to provide a rapid and robust estimate of the short
      term impacts of heat waves on mortality, to be used for communication within a
      heat warning system. The excess mortality during a heat wave is defined as the
      difference between the observed mortality over the period and the observed
      mortality over the same period during the N preceding years. This method was
      tested on 19 French cities between 1973 and 2007. In six cities, we compared the
      excess mortality to that obtained using a modelling of the temperature-mortality
      relationship. There was a good agreement between the excess mortalities estimated
      by the simple indicator and by the models. Major differences were observed during
      the most extreme heat waves, in 1983 and 2003, and after the implementation of
      the heat prevention plan in 2006. Excluding these events, the mean difference
      between the estimates obtained by the two methods was of 13 deaths [1:45]. A
      comparison of mortality with the previous years provides a simple estimate of the
      mortality impact of heat waves. It can be used to provide early and reliable
      information to stakeholders of the heat prevention plan, and to select heat waves
      that should be further investigated.

PMID- 22402696
TI  - Efficient [5 + 1]-strategy for the assembly of 1,8-naphthyridin-4(1H)-ones by
      domino amination/conjugate addition reactions of 1-(2-chloropyridin-3-yl)prop-2
      yn-1-ones with amines.
AB  - A facile synthetic approach for the synthesis of 1,8-naphthyridine-4(1H)-one
      derivatives via a catalyst free and Pd-supported tandem amination sequence is
      developed and described. In a case of aliphatic amines reaction proceeds in a
      catalyst free mode, however anilines demand Pd-supported reaction conditions.

PMID- 22402697
TI  - The lateral tarsal strip in ectropion surgery: is it effective when performed in
      isolation?
AB  - PURPOSE: The lateral tarsal strip (LTS) for involutional ectropion is often
      performed with a medial spindle (tarsoconjunctival diamond excision). We aimed to
      evaluate how well the LTS alone can achieve symptomatic relief. METHODS: A
      retrospective, comparative case series was performed on consecutive patients
      undergoing LTS alone or with medial spindle for involutional ectropion. Outcomes
      for LTS alone were clinically derived functional success (improvement in symptoms
      and aesthetic appearance) and anatomical success (judged by punctal position in
      the tear lake, punctal movement during blinking and absence of ectropion). We
      verified if these outcomes compared favourably with those of the patients who had
      undergone an LTS with medial spindle. Procedure selection was based on pre
      operative clinical examination, especially the lateral pinch and twist test (this
      is described). Complications were also recorded. RESULTS: Of 67 eyes, 23 had LTS
      alone and 44 had LTS with a medial spindle. Of those having LTS alone the
      functional success rate was 87% (95% CI (66.4, 97.2%)). This did not differ
      significantly from a success rate of 89% (75.4, 96.2%) in LTS with a medial
      spindle (P=0.99). A total of 78% (56.9, 92.5%) of patients undergoing LTS had a
      good anatomical result compared with 82% (67.3, 91.8%) of those who had an
      additional medial spindle (P=0.75). Complication rates were similar between the
      groups. CONCLUSION: Where the lateral pinch and twist test returns the eyelid to
      a good position, the LTS alone can suffice for the management of involutional
      ectropion.

PMID- 22402699
TI  - Histological findings of birdshot chorioretinopathy in an eye with ciliochoroidal
      melanoma.
AB  - PURPOSE: To describe the histological findings of birdshot chorioretinopathy.
      DESIGN/PARTICIPANT: This is a case study of a single patient who has both
      birdshot chorioretinopathy and ciliochoroidal melanoma. METHODS: A 55-year-old
      woman who was HLA-A29 positive and had birdshot chorioretinopathy had a large
      ciliochoroidal melanoma (T4b N0 M0) and underwent enucleation. OUTCOME MEASURES:
      Using histopathology, we hope to further define the pathological findings in an
      eye with both birdshot chorioretinopathy and coexistant ciliochoroidal melanomas.
      RESULTS: The eye showed a ciliochoroidal melanoma. In addition, elsewhere, there
      were multiple choroidal nodules of lymphocytes that showed the presence of CD3
      positive cells, which also stained for CD4 or CD8. There were only a few CD20
      positive B cells and rare CD68-positive histiocytes. No granulomas were present.
      DISCUSSION: To our knowledge, there are only two previous reports describing the
      histological findings in birdshot chorioretinopathy: one that was HLA-A29
      negative showing choroidal granulomas and another that was HLA-A29 positive
      exhibiting histological findings similar to our case. Incidentally, the latter
      case had a history of cutaneous melanoma. CONCLUSION: Birdshot chorioretinopathy
      is a nongranulomatous nodular infiltration of the choroid.

PMID- 22402700
TI  - 'Poppers maculopathy'--an emerging ophthalmic reaction to recreational substance
      abuse.

PMID- 22402702
TI  - Current concepts and future directions in the pathogenesis and management of non
      infectious uveitis.

PMID- 22402703
TI  - The clinical value of in vivo confocal microscopy for diagnosis of ocular surface
      squamous neoplasia.
AB  - PURPOSE: To determine the reliability and efficiency of in vivo confocal
      microscopy for the diagnosis of ocular surface squamous neoplasia (OSSN).
      METHODS: A case series with five consecutive cases of OSSN were investigated
      retrospectively, of which the characteristics and subspecial types had been
      estimated by in vivo confocal microscopy before surgery. The structure and
      cellular features of OSSN were analyzed with other examinations, such as anterior
      segment optical coherence tomography (AS-OCT), and confirmed by histopathological
      biopsy. RESULTS: The tumors revealed red gelatinous surfaces with vascular
      dilatation on the ocular surface of the conjunctival and corneal epithelium in
      anterior segment photography. Involvement of only corneal epithelium was observed
      by AS-OCT in three cases, whereas the Bowman's layer and anterior stroma were
      also invaded in the other two cases. In vivo confocal microscopy showed cellular
      anisocytosis and enlarged nuclei with high nuclear to cytoplasmic ratio in three
      cases diagnosed as conjunctival intraepithelial neoplasia; moreover, nests were
      partially formed by isolated keratinized, binucleated, and actively mitotic
      dysmorphic epithelial cells in the other two cases diagnosed as carcinoma in situ
      and ocular surface squamous carcinoma (OSSC). The characteristics assessed from
      histopathological biopsy were similar to that revealed by in vivo confocal
      microscopy in all five cases. CONCLUSION: In vivo confocal microscopy analysis of
      cytological characteristics of OSSN is a safe, relatively noninvasive, and
      effective diagnostic tool in detecting characteristics of OSSN before surgical
      resection. Although in vivo confocal microscopy cannot replace excisional biopsy
      for definitive diagnosis, it can be valuable for initial diagnosis and management
      of patients with OSSN.

PMID- 22402704
TI  - Re: Predictive factors and outcomes for posterior segment intraocular foreign
      bodies.

PMID- 22402705
TI  - PLMLA: prediction of lysine methylation and lysine acetylation by combining
      multiple features.
AB  - Post-translational lysine methylation and acetylation are two major modifications
      of lysine residues. They play critical roles in various biological processes,
      especially in gene regulation. Identification of protein methylation and
      acetylation sites would be a foundation for understanding their modification
      dynamics and molecular mechanism. This work presents a method called PLMLA that
      incorporates protein sequence information, secondary structure and amino acid
      properties to predict methylation and acetylation of lysine residues in whole
      protein sequences. We apply an encoding scheme based on grouped weight and
      position weight amino acid composition to extract sequence information and
      physicochemical properties around lysine sites. The prediction accuracy for
      methyllysine and acetyllysine are 83.02% and 83.08%, respectively. Feature
      analysis reveals that methyllysine is likely to occur at the coil region and
      acetyllysine prefers to occur at the helix region of protein. The upstream
      residues away from the central site may be close to methylated lysine in three
      dimensional structure and have a significant influence on methyllysine, while the
      positively charged residues may have a significant influence on acetyllysine. The
      online service is available at http://bioinfo.ncu.edu.cn/inquiries_PLMLA.aspx.

PMID- 22402707
TI  - Synthesis, crystal structure, spectroscopic and electrochemical properties, and
      H2-evolving activity of a new [PtCl(terpyridine)]+ derivative with viologen-like
      redox properties.
AB  - A new Pt(II)-based metalloviologen analog, [PtCl(Mepytpy)](2+) (abbreviated as
      PV(2+); Mepytpy(+) = 4'-(4-methyl-pyridinio)-2,2':6',2''-terpyridine), was
      synthesized and its spectroscopic and electrochemical properties were
      investigated. The structures of Mepytpy(+) and PV(2+) were solved by single
      crystal X-ray diffraction analysis. Electrochemical studies in DMF (N,N
      dimethylformamide) revealed that both the first and second reduction potentials
      of PV(2+) (E = -0.87 V vs. Fc/Fc(+) for PV(2+)/PV(+); E = -1.31 V vs. Fc/Fc(+)
      for PV(+)/PV(0)) are nearly consistent with those of methylviologen (N,N'-dimetyl
      4,4'-bipyridinium, MV(2+)) (E = -0.90 V vs. Fc/Fc(+) for MV(2+)/MV(+); E = -1.28
      V vs. Fc/Fc(+) for MV(+)/MV(0)), where the first reduction of PV(2+) is assigned
      as the reduction at the Mepytpy(+) ligand bound to the Pt(ii) ion. Upon the
      addition of a reducing agent Na(2)S(2)O(4) into an aqueous acetate buffer
      solution (pH = 5.0) of PV(2+), the generation of one-electron-reduced radical
      species (PV(+)) was spectrophotometrically observed and was assigned based on the
      time-dependent density functional theory (TD-DFT) calculations. The H(2)-evolving
      activity of PV(2+) was evaluated in the presence of a sacrificial electron donor
      (EDTA) in an aqueous acetate buffer solution (pH = 5.0). It was found that the
      stability of the metalloviologen PV(2+) during the photolysis is much higher than
      that of the parent compound [PtCl(tpy)](+).

PMID- 22402706
TI  - Delayed preattentional functioning in early psychosis patients with cannabis use.
AB  - RATIONALE: Cannabis use is prevalent among the early psychosis (EP) population.
      The event-related potentials, mismatch negativity (MMN) and P3a are reduced in
      EP. Cannabinoids have been shown to modulate N-methyl-D-aspartate receptors which
      are involved in MMN generation. OBJECTIVES: This study is the first to
      investigate the effects of cannabis use on MMN/P3a in EP. METHODS: EP was defined
      as a history of psychosis or psychotic symptoms with no progression to date to
      chronic schizophrenia. Twenty-two EP patients with cannabis use (EP + CANN), 22
      non-cannabis-using EP patients (EP-CANN) and 21 healthy controls participated in
      this study. MMN/P3a was elicited using a two-tone, auditory paradigm with 8%
      duration deviants. RESULTS: As expected, EP-CANN showed marked reductions in
      MMN/P3a amplitudes compared to controls. However, EP + CANN showed evidence of a
      different pattern of neurophysiological expression of MMN/P3a compared to non
      using patients, most notably in terms of delayed frontal MMN/P3a latencies.
      CONCLUSIONS: This study provides further evidence that MMN/P3a deficits are
      present during early psychosis and suggests that this biomarker may have utility
      in differentiating substance- from non-substance-related psychoses.

PMID- 22402709
TI  - Enhanced visual feedback for slip prevention with a prosthetic hand.
AB  - BACKGROUND: Upper limb amputees have no direct sense of the grip force applied by
      a prosthetic hand; thus, precise control of the applied grip force is difficult
      for amputees. Since there is little object deformation when rigid objects are
      grasped, it is difficult for amputees to visually gauge the applied grip force in
      this situation. OBJECTIVES: To determine if the applied grip force from a
      prosthetic hand can be visually displayed and used to more efficaciously grasp
      objects. STUDY DESIGN: Experimental controlled trial. METHODS: Force feedback is
      used in the control algorithm for the prosthetic hand and supplied visually to
      the user through a bicolor LED experimentally mounted to the thumb. Several
      experiments are performed by able-bodied test subjects to rate the usefulness of
      the additional visual feedback when manipulating a clearly visible, brittle
      object that can break if grasped too firmly. A hybrid force-velocity sliding mode
      controller is used with and without additional visual force feedback supplied to
      the operators. RESULTS: Subjective evaluations and success rates from the test
      subjects indicate a statistically significant reduction in breaking the grasped
      object when using the prosthesis with the extra visual feedback. CONCLUSIONS: The
      additional visual force feedback can effectively facilitate the manipulation of
      brittle objects. Clinical relevance The novel approach of this research is the
      implementation of a noninvasive, effective and economic technique to visually
      indicate the grip force applied by a prosthetic hand to upper limb amputees. This
      technique provides a statistically significant improvement when handling brittle
      objects.

PMID- 22402710
TI  - Selection of an above or below-ankle orthosis for individuals with neuropathic
      partial foot amputation: a pilot study.
AB  - BACKGROUND: Little evidence exists for the orthotic management for individuals
      diagnosed with diabetic neuropathy and partial foot amputation. OBJECTIVE: This
      pilot study examined differences in balance and pressure distribution while
      individuals wore foot orthoses inside shoes (BA) and this same orthosis combined
      with an above-ankle (AABA) orthosis. STUDY DESIGN: Within-group repeated measures
      crossover design. METHODS: Participants with transmetatarsal amputation were
      assessed during randomized visits with the two interventions. Using a motion
      analysis system and force plates, we computed the instantaneous inclination angle
      between the center of mass and center of pressure to quantify balance. The F-Scan
      in-shoe sensor system was used to measure plantar pressures. RESULTS: Improvement
      in balance was measured with the use of the AABA orthosis for the participant who
      had the greatest time from the timed up and go test (TUG). Plantar pressure
      during terminal stance did not change between the two conditions. And, lack of
      ankle mobility appears to lead to less compliance. CONCLUSION: Only individuals
      with reduced mobility may have improved balance with an orthosis that extends
      above the ankle. The TUG score may be an effective clinical exam to differentiate
      those individuals who may benefit from an AABA design as compared to a BA design.
      CLINICAL RELEVANCE: Orthotic interventions aim to improve balance and distribute
      plantar pressures. This study suggests that the different effects on balance
      while walking with the BA and AABA devices are individually specific and the TUG
      outcome measure may provide a useful means to determine the appropriate
      intervention.

PMID- 22402711
TI  - Toxicity assessment of sediments associated with the wreck of s/s Stuttgart in
      the Gulf of Gdansk (Poland).
AB  - The paper presents the results of toxicity determinations carried out on sediment
      samples collected in the vicinity of the wreck of the German s/s Stuttgart (the
      southern part of the Gulf of Gdansk, off the Polish coast) in relation to the
      determination of polycyclic aromatic hydrocarbons (PAHs). The toxicity of surface
      and core sediment samples was assessed using two biotest organisms-the
      bioluminescent bacteria Vibrio fischeri and the ostracod Heterocypris
      incongruens. PAH levels in these samples were determined by GC-MS. The surface
      sediments collected at W2 (ca. 34 m north of the shipwreck) and W4 (ca. 415 m
      north-east of the wreck) as well as the core sediments collected at WR3 (ca. 400
      m north-east of the wreck) were the most heavily polluted with substances toxic
      to the biotest organisms. The chronic and acute toxicities in the case of most of
      the surface sediment samples studied are correlated. This may suggest that not
      only hydrophobic chemicals (like PAHs from fuel residues) but also more polar
      chemicals (resulting from the conversion of aromatic hydrocarbons) are
      responsible for the toxicity levels found. There is a clear dependence between
      the levels of chronic toxicity and PAH concentrations in the core sediment
      samples. In addition, a simultaneous decrease in the PAH content and chronic
      toxicity was noted in all the core sediment samples at depths below 80 cm.

PMID- 22402712
TI  - Ferretting out the facts behind the H5N1 controversy.
AB  - Recent recommendations by the National Science Advisory Board for Biosecurity
      (NSABB) to redact key methodological details of two studies involving mammal-to
      mammal transmission of the H5N1 (H5) subtype influenza viruses, has led to a
      temporary moratorium on all research involving live H5N1 or H5 HA reassortant
      viruses shown to be transmissible in ferrets. Herein, I review the events which
      led to this impasse and comment on their impact.

PMID- 22402714
TI  - [Perspectives of therapy development from academia].

PMID- 22402713
TI  - AV interval optimization using pressure volume loops in dual chamber pacemaker
      patients with maintained systolic left ventricular function.
AB  - BACKGROUND: Atrioventricular (AV) interval optimization is often deemed too time
      consuming in dual-chamber pacemaker patients with maintained LV function. Thus
      the majority of patients are left at their default AV interval. OBJECTIVE: To
      quantify the magnitude of hemodynamic improvement following AV interval
      optimization in chronically paced dual chamber pacemaker patients. PATIENTS AND
      METHODS: A pressure volume catheter was placed in the left ventricle of 19
      patients with chronic dual chamber pacing and an ejection fraction >45 %
      undergoing elective coronary angiography. AV interval was varied in 10 ms steps
      from 80 to 300 ms, and pressure volume loops were recorded during breath hold.
      RESULTS: The average optimal AV interval was 152 +/- 39 ms compared to 155 +/- 8
      ms for the average default AV interval (range 100-240 ms). The average
      improvement in stroke work following AV interval optimization was 935 +/- 760
      mmHg/ml (range 0-2,908; p < 0.001), which translates into an average improvement
      of 14 +/- 9 % (range 0-28). A 10 ms variation of the AV interval changes the
      average stroke work by 207 +/- 162 mmHg/ml. AV interval optimization also leads
      to improved systolic dyssynchrony indices (17.7 +/- 7.0 vs. 19.4 +/- 7.1 %; p =
      0.01). CONCLUSION: The overall hemodynamic effect of AV interval optimization in
      patients with maintained LV function is in the same range as for patients
      undergoing cardiac resynchronization therapy for several parameters. The positive
      effect of AV interval optimization also applies to patients who have been
      chronically paced for years.

PMID- 22402715
TI  - [Nurturing clinician investigators is the best way to promote innovative drug
      development from academia].
AB  - Clinical research in Japan is still lacking in quality and quantity, and that
      situation is worsening. One important cause of those problems is the dearth of
      clinician-investigators. A recent change in the system for post-graduate clinical
      training affected the career paths of medical residents and reduced the number of
      young doctors who enter graduate school. Even those who are interested in
      clinical research now have incentives to avoid graduate school. In Japan, 19th
      century biological absolutism is still the dominant paradigm in the medical
      research community. Science for public health in the 21st century will benefit
      from a probabilistic paradigm, which can help to restore an appropriate balance
      between basic sciences and clinical research. Research done by clinician
      investigators should be based on clinical questions that arise in medical
      practice. That research includes investigation of disease and practice,
      exploration of associations between causes and outcomes, evaluation of diagnostic
      tests, and studies of the efficacy of treatments and prevention strategies. We
      emphasize the importance of nurturing clinician-investigators for the development
      of clinical research in Japan. This may not be the fastest way to promote
      innovative drug development from academia, but it is certainly the best.

PMID- 22402716
TI  - [Insights into neurological drug development in Japan].
AB  - Neurological disorders have varying prevalence rates and cause short- and long
      term impairments and disabilities. These disorders involve high costs and impose
      burdens on patients, caregivers, and society. Therefore, continued research and
      new therapeutic development in these areas have been expected worldwide.
      Recently, much attention has been paid to neurological drug development, and
      pharmaceutical companies are conducting many clinical trials in neurological
      fields. Industry-sponsored clinical trials have been performed not only in North
      America and western Europe but also in the so-called emerging regions such as the
      eastern European, Latin American, and Asian countries in recent years. In Japan,
      although the number of global clinical trials has increased in recent years,
      there is still a large gap between Japan and the US or European countries with
      regard to access to neurological drugs. In this article, we have summarized the
      status of new drug development for neurological disorders and the delays in
      neurological drug development in Japan. We have also discussed future tasks,
      including those for academia, related to promoting clinical trials in
      neurological fields in Japan.

PMID- 22402717
TI  - [Disease-modifying therapy for spinal and bulbar muscular atrophy (SBMA)].
AB  - Neurodegenerative diseases have long been construed as incurable disorders.
      However, therapeutic developments for these diseases are now facing a turning
      point, that is, analyses of cellular and animal models have provided insights
      into the pathogenesis of neurodegenerative diseases and have indicated rational
      therapeutic approaches. Spinal and bulbar muscular atrophy (SBMA) is an adult
      onset motor neuron disease characterized by slowly progressive muscle weakness
      and atrophy. This disease is caused by the expansion of a trinucleotide CAG
      repeat within the androgen receptor (AR) gene. The results of animal studies
      suggest that testosterone-dependent nuclear accumulation of the pathogenic AR
      protein is a fundamental step in the neurodegenerative process. Androgen
      deprivation with a luteinizing hormone-releasing hormone (LHRH) analogue
      suppresses the toxicity of the mutant AR in animal models of SBMA. In a phase 3
      trial, 48 weeks of treatment with leuprorelin acetate, an LHRH analogue, tended
      to improve swallowing function in a subgroup of SBMA patients with disease
      duration less than 10 years but did not significantly affect the total
      population. Disease duration might influence the efficacy of leuprorelin acetate,
      and therefore, a further clinical trial that involves sensitive outcome measures
      is in progress. Advances in basic and clinical research on SBMA are now paving
      the way for the clinical application of pathogenesis-targeting therapies. To
      optimize translational research related to the process of testing candidate
      therapies in humans, it is important to identify biomarkers that can be used as
      surrogate endpoints in clinical trials for neurodegenerative diseases.

PMID- 22402718
TI  - [Hepatocyte growth factor therapy for amyotrophic lateral sclerosis].
AB  - Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder
      characterized by the death of upper and lower motor neurons. Approximately 20% of
      familial ALS cases are caused by mutations in the superoxide dismutase 1 (SOD1)
      gene. We generated rats that express a human SOD1 transgene with two different
      ALS-associated mutations and found that these rats develop remarkable motor
      neuron degeneration and paralysis. This rat model, because of the larger size of
      the animals as compared to ALS-affected mice, will facilitate studies involving
      manipulation of the cerebrospinal fluid (CSF) (e.g., implantation of intrathecal
      catheters for chronic therapeutic studies; CSF sampling) or spinal cord (e.g.,
      direct administration of viral- and cell-mediated therapies). The hepatocyte
      growth factor (HGF) is one of the most potent survival-promoting factors for
      motor neurons. To examine its protective effect on motor neurons and its
      therapeutic potential, we administered human recombinant HGF (hrHGF) to the
      transgenic rats, by continuous intrathecal delivery, for 4 weeks from the onset
      of paralysis. Intrathecal administration of hrHGF attenuated motor neuron
      degeneration and prolonged the duration of the disease 62.7% compared with the
      contrast group. Our results indicated the therapeutic efficacy of continuous
      intrathecal administration of hrHGF in ALS rats. To explore the potential use of
      this treatment strategy in humans, we induced a contusive cervical spinal cord
      injury in the common marmoset, a primate, and then administered hrHGF
      intrathecally. The intrathecal administration of hrHGF promoted functional
      recovery. These projects have been supported by the "Super Special Consortium for
      Supporting the Development of Cutting-edge Medical Care" (tokku), a special
      program organized by the Cabinet Office of the Japanese government (research
      representative: Hideyuki Okano, M.D., Ph.D., Professor at Keio University).

PMID- 22402719
TI  - [Sialic Acid supplementation therapy for distal myopathy with rimmed vacuoles].
AB  - Distal myopathy with rimmed vacuoles (DMRV), also called hereditary inclusion
      body myopathy, is an autosomal recessive disease that typically affects tibialis
      anterior and hamstring muscles in young adults although other muscles are also
      involved in later stages. The disease is caused mostly by missense mutations in
      the GNE gene that encodes a protein with two enzymatic activities in sialic acid
      biosynthetic pathway: UDP-GlcNAc 2-epimerase and ManNAc kinase, respectively
      catalyzing the rate-limiting step and the subsequent reaction. Accordingly,
      sialic acid production is reduced in patients' cells and cells are
      hyposialylated. We have previously shown that this hyposialylation status can be
      recovered by simply giving sialic acid, suggesting that hyposilylation status in
      the muscle should be the cause of myopathy. In support of this notion, myopathic
      manifestations were virtually completely suppressed by oral administration of
      sialic acid in our DMRV model mice. Similar efficacy was seen also by ManNAc,
      precursor of sialic acid, or sialyllactose, a conjugate form of sialic acid.
      Based upon these in vitro and in vivo results, phase I clinical trial for sialic
      acid supplementation therapy for human patients was conducted in Japan in 2011.
      Another phase I trial, using slow release tablets of sialic acid, is currently in
      progress in the US. Hopefully, phase II trial to see the efficacy of the therapy
      will be initiated soon.

PMID- 22402720
TI  - [Neural mechanisms for navigation].
AB  - To examine the neural basis of navigation we recorded the activity of neurons in
      the monkey medial parietal region (MPR) while monkeys actively navigated through
      a virtual environment. We found navigation neurons whose responses to the same
      movement at the same location were modulated depending on the route that the
      monkey was currently taking, that is, in a route-selective manner. The reversible
      inactivation of MPR neurons by muscimol resulted in a monkey becoming lost during
      the navigation task trial. These results suggest that MPR plays a critical role
      in navigation by integrating location information and self-movement information.

PMID- 22402721
TI  - [Inflammatory mechanisms in amyotrophic lateral sclerosis].
AB  - Neuroinflammation is a pathological hallmark in human amyotrophic lateral
      sclerosis (ALS) patients and in the transgenic models of the disease. The
      importance of glial cell activation and pro-inflammatory cytokines in ALS has
      been confirmed by numerous studies. For instance, tumor necrosis factor-alpha
      (TNF-alpha), a major pro-inflammatory cytokine, activates microglia and cause
      neurotoxicity in motor neurons. More recently, the relationship of nuclear factor
      kappaB (NF-kappaB) and motor neuron degeneration has garnered attention since
      optineurin (OPTN) mutations were reported in familial ALS. OPTN negatively
      regulates TNF-alpha-induced NF-kappaB activation, but OPTN mutations can lead to
      dysinhibition of NF-kappaB-induced neurotoxicity. Notably, OPTN-positive
      inclusions are observed not only in familial ALS with OPTN mutation but also in
      sporadic ALS and in familial ALS with SOD1 and fused in sarcoma mutations,
      suggesting that OPTN- and NF-kappaB-related pathways are relevant to the general
      pathomechanisms of ALS. In this review, we discuss inflammatory aspects of ALS
      comprising the roles of cytokines, glial cells, and T cells.

PMID- 22402722
TI  - [Role of mitophagy in hereditary Parkinson's disease].
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease. The
      majority of PD cases are sporadic; however, the discovery of genes linked to rare
      familial forms of the disease has provided crucial insight into the molecular
      mechanisms of disease pathogenesis. PINK1 and PARKIN are causal genes for
      hereditary (i. e., autosomal recessive) early-onset PD. In 2010, intense efforts
      by our laboratory and several other groups have revealed the mechanism by which
      PINK1 and Parkin maintain mitochondrial integrity. The essence of the model is
      that PINK1 is rapidly and constitutively degraded under steady-state conditions
      in a mitochondrial membrane potential (DeltaPsim)-dependent manner and that a
      loss in DeltaPsim stabilizes PINK1 on damaged mitochondria, and then recruits
      Parkin from the cytosol to the mitochondria for proteasomal and autophagic
      degradation. Recently, a pharmacological approach using various chemical reagents
      such as valinomycin, nigericin, 2-deoxy-D-glucose, and oligomycin demonstrated
      that Parkin recruitment is voltage-dependent and independent of changes in ATP or
      pH. Moreover, F1-ATPase inhibitor azide recruited Parkin to the mitochondria only
      in rho<sup>0</sup> cells, which lack mtDNA and a functional electron transport
      chain. These results confirm that DeltaPsim is the most important factor for the
      discrimination of damaged mitochondria from their healthy counterparts. Here we
      provide an overview of how PINK1 and Parkin identify, label and clear
      damaged/depolarized mitochondria, focusing on the role of mitochondrial autophagy
      (mitophagy).

PMID- 22402723
TI  - [The present status and trend of brain tumors based on the data of the Brain
      Tumor Registry of Japan].
AB  - The Brain Tumor Registry of Japan (BTRJ) was founded in 1974 to investigate the
      statistical data of brain tumors in Japan. The 12th edition of the report was
      published as a supplement of the official journal of the Japan Neurosurgical
      Society, Neurologia medico-chirurgica, in October 2009. It contains the
      statistical data of 82,844 patients with primary or metastatic brain tumors
      registered between 1984 and 2000. The data represent the statistics of brain
      tumors such as the frequency and the anatomical distribution, patient age and
      sex, and survival rate in the magnetic resonance imaging (MRI) era. Among the
      registered cases, 65,677 were primary brain tumors. Meningioma was the most
      frequent, and it accounted for 27.1%, followed by glioma (26.6%), pituitary
      adenoma (18.2%), and schwannoma (10.5%). Among the patients who were under the
      age of 15 years the most frequent tumor was glioma (57.2%), while meningioma
      accounted for 46.3% among those over the age of 70 years. Compared with the data
      of the Central Brain Tumor Registry of the United States, glioma and meningioma
      were less frequent and pituitary adenoma and germ cell tumors were much more
      frequent in Japan. Both statistical registries showed that the frequency of
      benign brain tumors tends to increase and that of malignant tumors has decreased.
      In 2009, the BTRJ started the on-line registration, and most cases of brain
      tumors can be registered with the cooperation of all neurosurgeons in Japan.

PMID- 22402724
TI  - [Slowly progressive expanding hematoma in the Basal Ganglia: a report of 3 cases
      and a literature review].
AB  - We demonstrate and discuss slowly progressive expanding hematoma (SPEH) in the
      basal ganglia, which expands over 2 weeks. To our knowledge, there have been only
      5 cases of sudden-onset SPEH of the basal ganglia. To this, we add 3 cases
      admitted our hospitals because of putaminal hemorrhage within 1.5 hours of onset.
      All hematomas exhibited "2 components of hematoma sign" on initial CT scans,
      which we termed the "TCH sign" characterized as an anterolateral fluid portion
      and a posteromedial solid portion. Follow-up CT scans revealed gradual expansion
      of the fluid component of the hematoma without rebleeding for the subacute phase.
      Two cases were treated surgically. The first case, a 47-year-old man, underwent
      ultrasonically guided hematoma aspiration on day 17 and the second case, a 37
      year-old man, underwent hematoma removal by craniotomy on day 23 after onset.
      Their postoperative courses were uneventful. The third case, a 57-year-old man,
      improved without surgical treatment and the hematoma dissolved completely within
      2 months. To an extent, the TCH sign on a CT scan can be related to SPEH. We
      reviewed previous reports, including those an chronic expanding intracerebral
      hematomas and chronic encapsulated intracerebral hematomas, and concluded that it
      requires approximately 1 month for encapsulation of the hematoma to emerge. We
      suggest a possible progressive mechanism of SPEH. At first, the hematoma is
      divided into a fluid and a solid portion. Local generation of osmotically active
      molecules by clot degradation may allow intravascular fluid to escape into the
      fluid portion of the hematoma. Edema fluid with leakage via the disrupted blood
      brain barrier may also aggravate the fluid portion of the hematoma. The
      continuing inflammatory response leads to the emergence of a hematoma capsule
      similar to the membrane observed in cases of chronic subdural hematoma, followed
      by the secondary causes of hematoma expansion. We discuss feasible timing and
      surgical treatment methods.

PMID- 22402725
TI  - [Effect of levetiracetam on intractable secondarily generalized seizure and
      depression].
AB  - Levetiracetam (brand name: E Keppra(r)) is a new antiepileptic drug marketed in
      Japan since 2010 1, 2). Clinical reports of its use in Japan are few. Our
      experience with levetiracetam in a patient with secondarily generalized seizures
      yielded interesting findings. The patient was a 62-year-old man receiving 4
      antiepileptic drugs and 9 psychotropic drugs for treatment of secondarily
      generalized seizures (due to a cerebral contusion that occurred 20 years ago) and
      associated depressive symptoms, mainly anxiety and insomnia. He begun to wobble
      and, his increasing gait disturbance led to frequent falls. He recently underwent
      emergency surgery for acute extradural hematoma due to head contusion.
      Concomitant administration of levetiracetam, initiated after surgery, resulted in
      control of the epilepsy, resolution of the depressive symptoms, and reduction of
      multiple drugs doses. The patient was able to return to normal activity. Control
      of his epilepsy was probably attributable to the following: (1) the antiepileptic
      effect of levetiracetam and (2) improvement of the seizure threshold by
      streamlining multiple concomitant drugs. Although the effect of levetiracetam on
      depression is unclear, it is worth noting that control of the patient's epilepsy
      produced an improvement in the symptoms of depression.

PMID- 22402726
TI  - Pathogenomics of Pasteurella multocida.
AB  - The first complete genome sequence of the P. multocida avian isolate Pm70 was
      reported in 2001. Analysis of the genome identified many predicted virulence
      genes, including two encoding homologues of the Bordetella pertussis filamentous
      haemagluttinins, and genes involved in iron transport and metabolism.
      Availability of the genome sequence allowed for a range of whole-genome
      transcriptomic and proteomic analyses and these have helped us understand how P.
      multocida responds to growth in the presence of antibiotics, under low iron
      conditions and in the host. Unfortunately, no new P. multocida genome sequences
      were determined during the rest of the decade, limiting any possible comparative
      genomic analyses until recently, when several new genome sequences have become
      available. Here we use the available data to identify a number of important
      similarities and differences between the strains and determine their phylogenetic
      relationships. Interestingly, based on the current data there is no clear
      correlation between phylogenetic relatedness and host predilection or disease.

PMID- 22402727
TI  - Anti-spastic effects of the direct application of vibratory stimuli to the
      spastic muscles of hemiplegic limbs in post-stroke patients: a proof-of-principle
      study.
AB  - OBJECTIVE: To investigate whether the direct application of vibratory stimuli
      inhibits spasticity in the hemiplegic upper limbs of post-stroke patients.
      DESIGN: A randomized controlled study. SUBJECTS: Thirty-six post-stroke patients.
      METHODS: Patients were randomly allocated to the "Rest group", "Stretch group",
      or "Direct application of vibratory stimuli group". After relaxing in a supine
      posture for 30 min, subjects received the interventions for 5 min. The Modified
      Ashworth Scale scores and F-wave parameters were recorded before, immediately
      after and 30 min after each intervention. RESULTS: The Rest group showed no
      significant changes in F-wave parameters and Modified Ashworth Scale scores. The
      Stretch group showed a tendency to decrease in F-wave amplitude and F/M ratio
      immediately after the intervention, but not 30 min later. The Direct application
      of vibratory stimuli group showed significant improvements in F-wave parameters
      and Modified Ashworth Scale scores immediately after the intervention, which
      remained 30 minutes later. The changes in F-wave parameters and Modified Ashworth
      Scale scores observed in the Direct application of vibratory stimuli group
      significantly differed from those in the Rest group and the Stretch group.
      CONCLUSION: The direct application of vibratory stimuli has anti-spastic effects
      in the hemiplegic upper limbs of post-stroke patients.

PMID- 22402728
TI  - Fabrication of "strong" columnar Cu2-xSe superstructures assisted by inorganic
      ligands.
AB  - In this report, Cu(2-x)Se nanoplates with columnar superstructures have been
      synthesized via a facile, "green", phosphine-free, low-cost colloidal method. An
      inorganic tin(iv) selenium complex (Sn(2)Se(6))(4-) was attached on the surfaces
      of Cu(2-x)Se nanoplates directly during the synthesis of Cu(2-x)Se nanoplates.
      With the assistance of (Sn(2)Se(6))(4-) complexes, Cu(2-x)Se nanoplates showed
      "strong" self-assembly behavior and the stability of Cu(2-x)Se nanoplate
      superstructures was increased. Such columnar superstructures were still kept even
      if most of the coordinating organic ligands were removed by washing. The
      mechanism of the formation of "strong" columnar Cu(2-x)Se superstructures had
      been studied. We found the "strong" self-assemblies of Cu(2-x)Se nanoplates were
      formed only with the coexistence of oleylamine (OAM) and Sn-X in the synthesis
      process. The inorganic ligand not only played a key role in the construction of
      the "strong" columnar Cu(2-x)Se superstructure but also greatly improved their
      superior electrical property.

PMID- 22402729
TI  - Fused ring aziridines as a facile entry into triazole fused tricyclic and
      bicyclic heterocycles.
AB  - The intramolecular dipolar cycloaddition of an azide with an alkyne has provided
      a useful entry into triazole fused tricyclic heterocycles containing both the
      triazole ring and the oxazolidin-2-one ring system. The requisite azido-alkynes
      have been prepared via a two-step sequence from fused ring aziridines. A series
      of 6-12 membered rings containing both the oxazolidinone and triazole rings have
      been prepared. These ring systems have been designed as conformationally
      restrained analogs of RNA-binding oxazolidinones.

PMID- 22402731
TI  - Profiling changes triggered during maturation of dendritic cells: a lipidomic
      approach.
AB  - Lipids are important in several biological processes because they act as
      signalling and regulating molecules, or, locally, as membrane components that
      modulate protein function. This paper reports the pattern of lipid composition of
      dendritic cells (DCs), a cell type of critical importance in inflammatory and
      immune responses. After activation by antigens, DCs undergo drastic phenotypical
      and functional transformations, in a process known as maturation. To better
      characterize this process, changes of lipid profile were evaluated by use of a
      lipidomic approach. As an experimental model of DCs, we used a foetal skin
      derived dendritic cell line (FSDC) induced to mature by treatment with
      lipopolysaccharide (LPS). The results showed that LPS treatment increased
      ceramide (Cer) and phosphatidylcholine (PC) levels and reduced sphingomyelin (SM)
      and phosphatidylinositol (PI) content. Mass spectrometric analysis of a total
      lipid extract and of each class of lipids revealed that maturation promoted clear
      changes in ceramide profile. Quantitative analysis enabled identification of an
      increase in the total ceramide content and enhanced Cer at m/z 646.6, identified
      as Cer(d18:1/24:1), and at m/z 648.6, identified as Cer(d18:1/24:0). The pattern
      of change of these lipids give an extremely rich source of data for evaluating
      modulation of specific lipid species triggered during DC maturation.

PMID- 22402732
TI  - HF-LPME as a green alternative for the preconcentration of nickel in natural
      waters.
AB  - In the last years, some analytical methodologies have been identified as a source
      of pollution, receiving increasing attention to decrease their impact on the
      environment. In this sense, the so-called solvent-less methodologies appear as a
      green alternative to reduce the volume of solvents used in many sample treatment
      procedures and, consequently, the volume of toxic wastes produced. Among these
      techniques, analytical methodologies based on liquid-phase microextraction are
      being continuously developed, although most applications are focused on organic
      compounds. In this work, a three-phase hollow-fibre liquid-phase microextraction
      (HF-LPME) system has been developed for the preconcentration of nickel in natural
      waters, prior to the analysis by atomic absorption spectrometry. Under optimum
      conditions, the new system allowed an enrichment factor of 29.80 to be obtained
      after 60 min of experiment, and it was successfully applied to the determination
      of nickel in both saline and non-saline water samples, at ppb and ppt levels. The
      results were compared with those obtained using a well-established methodology
      based on liquid solvent extraction showing no significant differences (alpha =
      0.05) between both values. In addition, the new HF-LPME presents the advantages
      of a green analytical technique, as its greenness profile shows, with the
      additional reduction of sample manipulation and time cost.

PMID- 22402734
TI  - Serial childhood BMI and associations with adult hypertension and obesity: the
      Fels Longitudinal Study.
AB  - Previous studies estimated critical periods of childhood BMI growth and linked
      these events to adult adiposity and cardiovascular health. We expand upon both
      results to link childhood BMI growth patterns with adult blood pressure (BP).
      Data from male and female participants in the Fels Longitudinal Study (FLS) were
      used to estimate childhood BMI growth curves, from which we isolate ages of
      childhood BMI divergence based upon adult BMI and BP measurements. Repeated
      measure analysis of variances models were used to estimate BMI growth curves from
      age 2 to age 17.5 based on both adult BMI (< 25 kg/m(2) or >= 25 kg/m(2)) and
      adult BP (< 120 mm Hg or >= 120 mm Hg for systolic BP (SBP); < 80 mm Hg or >= 80
      mm Hg for diastolic BP (DBP)). Participants with lower body weight throughout
      childhood had lower SBP and DBP in early adulthood. Any relationships between
      childhood adiposity and adult body weight and BP disappeared by age 60. These
      results were independent of adult BMI and were observed in both men and women.
      Increased adult BP has its genesis in part from increased childhood BMI.

PMID- 22402733
TI  - Effect of an environmental school-based obesity prevention program on changes in
      body fat and body weight: a randomized trial.
AB  - This study tested the efficacy of two school-based programs for prevention of
      body weight/fat gain in comparison to a control group, in all participants and in
      overweight children. The Louisiana (LA) Health study utilized a longitudinal,
      cluster randomized three-arm controlled design, with 28 months of follow-up.
      Children (N = 2,060; mean age = 10.5 years, SD = 1.2) from rural communities in
      grades 4-6 participated in the study. Seventeen school clusters (mean = 123
      children/cluster) were randomly assigned to one of three prevention arms: (i)
      primary prevention (PP), an environmental modification (EM) program, (ii) primary
      + secondary prevention (PP+SP), the environmental program with an added classroom
      and internet education component, or (iii) control (C). Primary outcomes were
      changes in percent body fat and BMI z scores. Secondary outcomes were changes in
      behaviors related to energy balance. Comparisons of PP, PP+SP, and C on changes
      in body fat and BMI z scores found no differences. PP and PP+SP study arms were
      combined to create an EM arm. Relative to C, EM decreased body fat for boys (-1.7
      +/- 0.38% vs. -0.14 +/- 0.69%) and attenuated fat gain for girls (2.9 +/- 0.22%
      vs. 3.93 +/- 0.37%), but standardized effect sizes were relatively small (<0.30).
      In conclusion, this school-based EM programs had modest beneficial effects on
      changes in percent body fat. Addition of a classroom/internet program to the
      environmental program did not enhance weight/fat gain prevention, but did impact
      physical activity and social support in overweight children.

PMID- 22402735
TI  - Weight loss induced by chronic dapagliflozin treatment is attenuated by
      compensatory hyperphagia in diet-induced obese (DIO) rats.
AB  - Dapagliflozin is a potent and selective sodium glucose cotransporter-2 (SGLT2)
      inhibitor which promotes urinary glucose excretion and induces weight loss. Since
      metabolic compensation can offset a negative energy balance, we explored the
      potential for a compensatory physiological response to the weight loss induced by
      dapagliflozin. Dapagliflozin was administered (0.5-5 mpk; p.o.) to diet-induced
      obese (DIO) rats with or without ad libitum access to food for 38 days. Along
      with inducing urinary glucose excretion, chronic administration of dapagliflozin
      dose-dependently increased food and water intake relative to vehicle-treated
      controls. Despite this, it reduced body weight by 4% (relative to controls) at
      the highest dose. The degree of weight loss was increased by an additional 9% if
      hyperphagia was prevented by restricting food intake to that of vehicle controls.
      Neither oxygen consumption (vO2) or the respiratory exchange ratio (RER) were
      altered by dapagliflozin treatment alone. Animals treated with dapagliflozin and
      pair-fed to vehicle controls (5 mpk PF-V) showed a reduction in RER and an
      elevation in nonfasting beta-hydroxybutyrate (BHBA) relative to ad libitum-fed 5
      mpk counterparts. Fasting BHBA was elevated in the 1 mpk, 5 mpk, and 5 mpk PF-V
      groups. Serum glucose was reduced in the fasted, but not the unfasted state.
      Insulin was reduced in the non-fasted state. These data suggest that in rodents,
      the persistent urinary glucose excretion induced by dapagliflozin was accompanied
      by compensatory hyperphagia, which attenuated the weight loss induced by SGLT2
      inhibition. Therefore, it is possible that dapagliflozin-induced weight loss
      could be enhanced with dietary intervention.

PMID- 22402736
TI  - Diet-induced weight loss in overweight or obese women and changes in high-density
      lipoprotein levels and function.
AB  - Diet-induced weight loss in women may be associated with decreases not only in
      plasma levels of low-density lipoprotein cholesterol (LDL-C), but also in high
      density lipoprotein cholesterol (HDL-C). Whether a decrease in HDL-C is
      associated with altered HDL function is unknown. One hundred overweight or obese
      women (age 46 +/- 11 years, 60 black; 12 diabetic) were enrolled in the 6-month
      program of reduced fat and total energy diet and low-intensity exercise. Serum
      cholesterol efflux capacity was measured in (3)H-cholesterol-labeled BHK cells
      expressing ABCA1, ABCG1, or SR-B1 transporters and incubated with 1%
      apolipoprotein B (apoB)-depleted serum. Antioxidant properties of HDL were
      estimated by paraoxonase-1 (PON1) activity and oxygen radical absorbance capacity
      (ORAC). Endothelial nitric oxide synthase (eNOS) activation was measured by
      conversion of L-arginine to L-citrulline in endothelial cells incubated with HDL
      from 49 subjects. Participants achieved an average weight loss of 2.2 +/- 3.9 kg
      (P < 0.001), associated with reductions in both LDL-C (-6 +/- 21 mg/dl, P =
      0.004) and HDL-C (-3 +/- 9 mg/dl, P = 0.016). Cholesterol efflux capacity by the
      ABCA1 transporter decreased by 10% (P = 0.006); efflux capacities by the ABCG1
      and SR-B1 transporters were not significantly altered. ORAC decreased by 15% (P =
      0.018); neither PON1 activity nor eNOS activation was significantly altered by
      reduction in HDL-C. Findings were similar for diabetic and nondiabetic subjects.
      Diet-induced weight loss in overweight or obese women is associated with a
      decrease in HDL-C levels, but overall HDL function is relatively spared,
      suggesting that decrease in HDL-C in this setting is not deleterious to
      cardiovascular risk.

PMID- 22402737
TI  - Weight loss is associated with increased serum 25-hydroxyvitamin D in overweight
      or obese women.
AB  - Low circulating concentrations of vitamin D metabolites have been associated with
      increased risk for several diseases and clinical conditions. Large observational
      studies and surveys have shown that obesity is independently associated with
      lower serum 25-hydroxyvitamin D (25(OH)D) concentration. Few studies have
      examined the effect of weight loss on serum 25(OH)D concentration. The purpose of
      this study was to prospectively examine the effect of weight loss on serum
      25(OH)D concentration. Data were collected from 383 overweight or obese women who
      participated in a 2-year clinical trial of a weight-loss program, in which 51% (N
      = 195) lost at least 5% of baseline weight by 24 months, 18% (N = 67) lost 5-10%,
      and 33% (N = 128) lost >10%. Women who did not lose weight at 24 months had an
      increase in serum 25(OH)D of 1.9 (9.7) ng/ml (mean (SD)); 25(OH)D increased by
      2.7 (9.1) ng/ml for those who lost 5-10% of baseline weight; and 25(OH)D
      increased by 5.0 (9.2) ng/ml for those who lost >10% of baseline weight (P =
      0.014). At baseline, 51% (N = 197) of participants met or exceeded the
      recommended serum concentration of 20 ng/ml. By study end, 64% (N = 230) of
      overweight or obese women met this goal, as well as 83% (N = 20) of those whose
      weight loss achieved a normal BMI. These findings suggest that weight loss,
      presumably associated with a reduction in body fat, is associated with increased
      serum 25(OH)D concentration in overweight or obese women.

PMID- 22402738
TI  - Relationship between sleep quality and quantity and weight loss in women
      participating in a weight-loss intervention trial.
AB  - Evidence suggests that individuals who report fewer total hours of sleep are more
      likely to be overweight or obese. Few studies have prospectively evaluated weight
      loss success in relation to reported sleep quality and quantity. This analysis
      sought to determine the association between sleep characteristics and weight loss
      in overweight or obese women enrolled in a randomized clinical trial of a weight
      loss program. We hypothesized that in overweight/obese women, significant weight
      loss would be demonstrated more frequently in women who report a better
      Pittsburgh Sleep Quality Index (PSQI) Global Score or sleep >7 h/night as
      compared to women who report a worse PSQI score or sleep <=7 h/night. Women of
      ages 45.5 +/- 10.4 (mean +/- SD) years and BMI of 33.9 +/- 3.3 (n = 245) were
      randomized and completed PSQI at baseline and 6 months; 198 had weight change
      assessed through 24 months. At baseline, 52.7% reported PSQI scores above the
      clinical cutoff of 5. Better subjective sleep quality increased the likelihood of
      weight-loss success by 33% (relative risk (RR), 0.67; 95% confidence interval
      (CI), 0.52-0.86), as did sleeping >7 h/night. A worse Global Score at 6 months
      was associated with a 28% lower likelihood of continued successful weight loss at
      18 months, but unassociated by 24 months. These results suggest that sleep
      quality and quantity may contribute to weight loss in intervention-based studies
      designed to promote weight control in overweight/obese adult women.

PMID- 22402739
TI  - Physical activity, sedentary time, and pericardial fat in healthy older adults.
AB  - Pericardial fat is emerging as a unique risk factor for coronary disease. We
      examined the relationship between objectively measured physical activity during
      free-living and pericardial fat. Participants were 446 healthy men and women
      (mean age = 66 +/- 6 years), without history or objective signs of cardiovascular
      disease (CVD), drawn from the Whitehall II epidemiological cohort. Physical
      activity was objectively measured using accelerometers (Actigraph GT3X) worn
      around the hip during waking hours for 7 consecutive days (average daily wear
      time = 889 +/- 68 min/day), and was classified as sedentary (<200 counts/min
      (cpm)), light (200-1,998 cpm), or moderate-vigorous physical activity (MVPA;
      >=1,999 cpm). Pericardial fat volume was measured in each participant using
      electron beam computed tomography. Average daily cpm in men was 338.0 +/- 145.0
      and in women 303.8 +/- 130.2. There was an inverse association between average
      cpm and pericardial fat (B = -0.070, 95% confidence interval (CI), -0.101, 
      0.040, P < 0.001), and this remained significant after adjusting for age, sex,
      registered wear time, BMI, lipids, glycemic control, blood pressure, smoking,
      statins, and social status. Both sedentary time (B = 0.081, 95% CI, 0.022, 0.14)
      and MVPA (B = -0.362, 95% CI, -0.527, -0.197) were also associated with
      pericardial fat, although associations for sedentary time did not remain
      significant after adjustment for MVPA. The inverse association between physical
      activity and pericardial fat was stronger among overweight and obese adults than
      in normal weight. Objectively assessed daily activity levels are related to
      pericardial fat in healthy participants, independently of BMI. This might be an
      important mechanism in explaining the association between physical activity and
      CVD prevention.

PMID- 22402740
TI  - Occurrence, distribution and bioaccumulation of antibiotics in the Haihe River in
      China.
AB  - The occurrence, distribution and bioaccumulation of 22 antibiotics, including
      eight fluoroquinolones (FQs), nine sulfonamides (SAs) and five macrolides (MLs),
      in the Haihe River were investigated. Surface water, sediment and fish samples
      were analyzed by HPLC-MS/MS. Ofloxacin, sulfamethoxazole, sulfadiazine,
      erythromycin and roxithromycin were found in all surface water samples. SAs were
      the predominant antibiotics in surface water samples in the mainstream of Haihe
      River, with the maximum concentration of 201 ng L(-1) for sulfamethoxazole.
      Compared with Haihe River, higher concentrations of antibiotics were found in the
      surface water samples in the Dagu and Chentaizi Drainage Rivers. The antibiotics
      pollution in the mainstream of Haihe River may derive from its tributaries,
      whereas the wastewater from fish ponds was not the main source of FQs, SAs and
      MLs in the river water. In sediment samples, FQs were the most frequently
      detected antibiotics and their concentrations were much higher than SAs and MLs.
      The high concentrations and detection frequencies of FQs in sediments indicate
      that sediments are an important reservoir for FQs as they are strongly adsorbed
      onto sediments. Ciprofloxacin and erythromycin exhibited potential
      bioaccumulation in crucian carp, with mean bioaccumulation factors of 3262 L kg(
      1) and 4492 L kg(-1), respectively.

PMID- 22402742
TI  - Construction of the real patient simulator system.
AB  - Simulation for perfusion education has been used for at least the past 25 years.
      The earlier models were either electronic (computer games) or fluid dynamic
      models and provided invaluable adjuncts to perfusion training and education. In
      2009, the *North Shore-LIJ Health System at Great Neck, New York, opened an
      innovative "Bioskill Center" dedicated to simulated virtual reality advanced
      hands-on surgical training as well as perfusion simulation. Professional cardiac
      surgical organizations now show great interest in using simulation for training
      and recertification. Simulation will continue to be the direction for future
      perfusion training and education. This manuscript introduces a cost-effective
      system developed from discarded perfusion products and it is not intended to
      detail the actual lengthy process of its construction.

PMID- 22402741
TI  - Disease-promoting and -protective genomic loci on mouse chromosomes 3 and 19
      control the incidence and severity of autoimmune arthritis.
AB  - Proteoglycan (PG)-induced arthritis (PGIA) is a murine model of rheumatoid
      arthritis. Arthritis-prone BALB/c mice are 100% susceptible, whereas the major
      histocompatibility complex-matched DBA/2 strain is completely resistant to PGIA.
      To reduce the size of the disease-suppressive loci for sequencing and to find
      causative genes of arthritis, we created a set of BALB/c.DBA/2
      congenic/subcongenic strains carrying DBA/2 genomic intervals overlapping the
      entire Pgia26 locus on chromosome 3 (chr3) and Pgia23/Pgia12 loci on chr19 in the
      arthritis-susceptible BALB/c background. Upon immunization of these subcongenic
      strains and their wild-type (BALB/c) littermates, we identified a major Pgia26a
      sublocus on chr3 that suppressed disease onset, incidence and severity via
      controlling the complex trait of T-cell responses. The region was reduced to 3
      Mbp (11.8 Mbp with flanking regions) in size and contained gene(s) influencing
      the production of a number of proinflammatory cytokines. Additionally, two
      independent loci (Pgia26b and Pgia26c) suppressed the clinical scores of
      arthritis. The Pgia23 locus (~3 Mbp in size) on chr19 reduced arthritis
      susceptibility and onset, and the Pgia12 locus (6 Mbp) associated with low
      arthritis severity. Thus, we have reached the critical sizes of arthritis
      associated genomic loci on mouse chr3 and chr19, which are ready for high
      throughput sequencing of genomic DNA.

PMID- 22402745
TI  - Surface characterization of imidazolium-based ionic liquids with cyano
      functionalized anions at the gas-liquid interface using sum frequency generation
      spectroscopy.
AB  - Advancement in the field of ionic liquid technology requires a comprehensive
      understanding of their surface properties, as a wide range of chemical reactions
      occur mainly at interfaces. As essential media currently used in several
      technological applications, their accurate molecular level description at the gas
      liquid interface is of utmost importance. Due to the high degree of chemical
      information provided in the vibrational spectrum, vibrational spectroscopy gives
      the most detailed model for molecular structure. The inherently surface-sensitive
      technique, sum frequency generation (SFG) spectroscopy, in combination with bulk
      sensitive vibrational spectroscopic techniques such as FTIR and Raman, has been
      used in this report to characterize the surface of cyano-containing ionic
      liquids, such as [BMIM][SCN], [BMIM][DCA], [BMIM][TCM] and [EMIM][TCB] at the gas
      liquid interface. By structural variation of the anion while keeping the cation
      constant, emphasis on the molecular arrangement of the anion at the gas-liquid
      interface is reported, and its subsequent role (if any) in determining the
      surface molecular orientation of the cation. Vibrational modes seen in the C-H
      stretching region revealed the presence of the cation at the gas-liquid
      interface. The cation orientation is independent of the type of cyano-containing
      anion, however, a similar arrangement at the surface as reported in previous
      studies was found, with the imidazolium ring lying flat at the surface, and the
      alkyl chains pointing towards the gas phase. SFG results show that all three
      anions of varying symmetry, namely, [DCA](-) (C(2v)), [TCM](-)(D(3h)) and [TCB](
      ) (T(d)) in ionic liquids [BMIM]DCA], [BMIM][TCM] and [EMIM][TCB] are
      significantly tilted from the surface plane, while the linear [SCN](-) in
      [BMIM][SCN] exhibited poor ordering, as seen in the absence of its C-N stretching
      mode in the SFG vibrational spectra.

PMID- 22402744
TI  - Pleiotropic effects of miR-183~96~182 converge to regulate cell survival,
      proliferation and migration in medulloblastoma.
AB  - Medulloblastomas are the most common malignant brain tumors in children. Several
      large-scale genomic studies have detailed their heterogeneity, defining multiple
      subtypes with unique molecular profiles and clinical behavior. Increased
      expression of the miR-183~96~182 cluster of microRNAs has been noted in several
      subgroups, including the most clinically aggressive subgroup associated with
      genetic amplification of MYC. To understand the contribution of miR-183~96~182 to
      the pathogenesis of this aggressive subtype of medulloblastoma, we analyzed
      global gene expression and proteomic changes that occur upon modulation of miRNAs
      in this cluster individually and as a group in MYC-amplified medulloblastoma
      cells. Knockdown of the full miR-183~96~182 cluster results in enrichment of
      genes associated with apoptosis and dysregulation of the PI3K/AKT/mTOR signaling
      axis. Conversely, there is a relative enrichment of pathways associated with
      migration, metastasis and epithelial to mesenchymal transition, as well as
      pathways associated with dysfunction of DNA repair in cells with preserved miR
      183 cluster expression. Immunocytochemistry and FACS analysis confirm induction
      of apoptosis upon knockdown of the miR-183 cluster. Importantly, cell-based
      migration and invasion assays verify the positive regulation of cell
      motility/migration by the miR-183 cluster, which is largely mediated by miR-182.
      We show that the effects on cell migration induced by the miR-183 cluster are
      coupled to the PI3K/AKT/mTOR pathway through differential regulation of AKT1 and
      AKT2 isoforms. Furthermore, we show that rapamycin inhibits cell
      motility/migration in medulloblastoma cells and phenocopies miR-183 cluster
      knockdown. Thus, the miR-183 cluster regulates multiple biological programs that
      converge to support the maintenance and metastatic potential of medulloblastoma.

PMID- 22402746
TI  - Palladium-catalyzed S-benzylation of unprotected mercaptobenzoic acid with benzyl
      alcohols in water.
AB  - Palladium-catalyzed S-benzylation of unprotected mercaptobenzoic acids with
      benzyl alcohols gave only S-benzylated mercaptobenzoic acids in good yields.
      Water may play an important role for the smooth generation of the (eta(3)
      benzyl)palladium species by activation of the hydroxyl group of the benzyl
      alcohol.

PMID- 22402747
TI  - Microstructure evolution and advanced performance of Mn3O4 nanomorphologies.
AB  - Mn(3)O(4) morphologies with tetragonal single-crystal nanostructures including
      nanoparticles, nanorods and nanofractals were successfully prepared by a widely
      applicable chemical reaction route. The morphologies were synthesized using the
      reactants MnCl(2).4H(2)O, H(2)O(2), and NaOH in a suitable surfactant and
      alkaline solution. The dripping speed of the NaOH solution plays an important
      role in the microstructure evolution of Mn(3)O(4) morphologies. The difference in
      the dripping speed of NaOH solutions leads to different Mn(3)O(4)
      nanomorphologies, which are called nanoparticles, nanorods and nanofractals. The
      average grain size of the Mn(3)O(4) nanoparticles ranged from a few to several
      tens of nanometers. The Mn(3)O(4) nanorods were smooth, straight, and the
      geometrical shape was structurally perfect. Their lengths ranged from several
      hundred nanometers to a few micrometers, and their diameters ranged from 10 nm to
      30 nm. The fractal branches of the Mn(3)O(4) nanofractals were a few micrometers
      in length and several hundred nanometers in width. The catalytic properties of
      these Mn(3)O(4) nanomorphologies for the degradation of phenol were evaluated in
      detail. The results indicated that the Mn(3)O(4) nanofractals possess remarkable
      catalytic activity for the degradation of phenol in water treatment.

PMID- 22402748
TI  - The role of trait emotional intelligence in the diagnostic cancer pathway.
AB  - PURPOSE: Trait emotional intelligence (trait EI) has been linked with
      psychological outcomes in a variety of settings; however, it has received little
      attention in the healthcare field. We investigated the relationship between trait
      EI and worry at different stages of the diagnostic cancer pathway. METHODS: We
      recruited 64 individuals attending an outpatient urology cancer investigation.
      Patients completed the Hospital Anxiety and Depression Scale, Trait Emotional
      Intelligence Questionnaire--Short Form and a single-item measure of
      arousal/pleasantness. Worry was assessed retrospectively for each stage of the
      pathway and concurrently for the stage of 'awaiting the specialist'. RESULTS:
      Trait EI was negatively associated with worry in the early stages of the
      diagnostic pathway ('deciding to see' and 'awaiting the general practitioner
      (GP)'; ps < 0.05) and was negatively linked to patients' worry while 'seeing the
      GP' (p = 0.051) after controlling for anxiety, depression, arousal and
      pleasantness. CONCLUSION: Low trait EI is predictive of increased worry levels in
      the early stages of the diagnostic cancer pathway. Individual differences in
      trait EI should be considered when communicating medical results to patients and
      in the development of interventions designed to reduce worry levels in patients
      entering the diagnostic cancer pathway.

PMID- 22402750
TI  - A qualitative exploration of the role of primary care in supporting colorectal
      cancer patients.
AB  - PURPOSE: To explore experiences and support needs of people with colorectal
      cancer, with a focus on identifying opportunities for primary care interventions.
      METHODS: We conducted a new qualitative analysis of an existing dataset,
      comprising semi-structured interview transcripts from 39 people with colorectal
      cancer from across the UK, interviewed in 2001-2002 for www.healthtalkonline.org
      . Then, we conducted semi-structured interviews with 30 people with colorectal
      cancer from North East Scotland and Glasgow in 2009 and analysed these new data
      to explore themes and challenge hypotheses that emerged from the Healthtalkonline
      data. RESULTS: Formal sources of support, including that from primary care, were
      valued by those who received them, but provision was described as sporadic both
      in 2002 and in 2009. However, more of the 2009 participants gave descriptions of
      specialist nurse and community nurse involvement, and telephone contact from
      general practitioners, which were welcomed. Improvements in meeting information
      needs, particularly on the issues of diet and sex, were identified by 2009. A
      recurring issue reported by patients was the distress experienced by their own
      friends and family; some patients found themselves having to provide, rather than
      receive, emotional support at this difficult time. CONCLUSIONS: There have been
      improvements in support for people with colorectal cancer since 2002, with more
      specialist and community nurse involvement, and telephone contact from general
      practitioners, but provision remains piecemeal. Patients would benefit if their
      families received support, and primary care may be in a good position to provide
      this. A proactive approach from general practitioners in the post-discharge
      period is valued.

PMID- 22402749
TI  - Outpatient and oral antibiotic management of low-risk febrile neutropenia are
      effective in children--a systematic review of prospective trials.
AB  - BACKGROUND: There is no consensus on whether therapeutic intensity can be reduced
      safely in children with low-risk febrile neutropenia (FN). Our primary objective
      was to determine whether there is a difference in efficacy between outpatient and
      inpatient management of children with low-risk FN. Our secondary objective was to
      compare oral and parenteral antibiotic therapy in this population. METHODS: We
      performed electronic searches of Ovid Medline, EMBASE, and the Cochrane Central
      Register of Controlled Trials, and limited studies to prospective pediatric
      trials in low-risk FN. Percentages were used as the effect measure. RESULTS: From
      7,281 reviewed articles, 16 were included in the meta-analysis. Treatment
      failure, including antibiotic modification, was less likely to occur in the
      outpatient setting compared with the inpatient setting (15 % versus 28 %, P =
      0.04) but was not significantly different between oral and parenteral antibiotic
      regimens (20 % versus 22 %, P = 0.68). Of the 953 episodes treated in the
      outpatient setting and 676 episodes treated with oral antibiotics, none were
      associated with infection-related mortality. CONCLUSION: Based on the combination
      of results from all prospective studies to date, outpatient and oral antibiotic
      management of low-risk FN are effective in children and should be incorporated
      into clinical care where feasible.

PMID- 22402752
TI  - Is access to the body structural description sensitive to a body part's
      significance for action and cognition? A study of the sidedness effect using
      feet.
AB  - There is evidence suggesting that viewing hands triggers automatic access to the
      Body Structural Description, a visual-spatial representation of human body parts
      configuration. Hands, however, have a special representational status within the
      brain because of their significance for action and cognition. We tested whether
      feet, less important in gestural and object-directed action, would similarly show
      automatic access to the Body Structural Description. Positive evidence of that
      would be finding a Sidedness effect (Ottoboni et al. J Exp Psychol Hum Percept
      Perform 31:778-789, 2005), a Simon-like paradigm previously used to study
      automatic hand recognition. This effect demonstrates that processing hands
      generates spatial codes corresponding to the side of the body on which the hand
      would be located within the Body Structural Description map. Feet were shown with
      toes pointing upwards (Experiment 1), without any connection to the ankle and the
      leg (Experiment 2) and with toes pointing downwards (Experiment 3). Results
      revealed a Sidedness effect in both Experiments 1 and 3: spatial compatibility
      occurred according to the side of the body that each foot would assume within the
      Body Structural Description. In Experiment 2, as already found in stimuli
      similarly featured, no effect emerged, due to the lack of the necessary
      anatomical links connecting the foot to a body. Results suggest that body parts
      with variable degrees of significance for action and cognition can access
      automatically the Body Structural Description hence reinforcing the hypothesis of
      its pure visuo-spatial nature.

PMID- 22402753
TI  - The degradation mechanism of phenol induced by ozone in wastes system.
AB  - A distinct understanding for the degradation mechanism of phenol induced by ozone
      is very essential because the ozonation process, one of the advanced oxidation
      processes (AOPs), is attractive and popular in wastewater treatment. In the
      present work, the detailed reactions of ozone and phenol are investigated
      employing the density functional theory B3LYP method with the 6-311++G (d, p)
      basis set. The profiles of the potential energy surface are constructed and the
      possible reaction pathways are indicated. These detailed calculation results
      suggest two degradation reaction mechanisms. One is phenolic H atom abstraction
      mechanism, and the other is cyclo-addition and ring-opening mechanism.
      Considering the effect of solvent water, the calculated energy barriers and
      reaction enthalpies for the reaction of O3 and phenol in water phase are both
      lower than those in gas phase, though the degradation mechanisms are not changed.
      This reveals that these degradation reactions are more favorable in the water
      solvent. The main reaction products are C(6)H(5)OO. radical, a crucial precursor
      for forming PCDD/Fs and one ring-opening product, which are in good agreement
      with the experimental observations.

PMID- 22402754
TI  - In silico investigation of interactions between human cannabinoid receptor-1 and
      its antagonists.
AB  - Cannabinoid receptor-1 (CB(1)) is widely expressed in the central nervous system
      and plays a vital role in regulating food intake and energy expenditure. CB(1)
      antagonists such as Rimonabant have been used in clinic to inhibit food intake,
      and therefore reduce body weight in obese animals and humans. To investigate the
      binding modes of CB(1) antagonists to the receptor, both receptor- and ligand
      based methods were implemented in this study. At first, a pharmacophore model was
      generated based on 31 diverse CB(1) antagonists collected from literature. A test
      set validation and a simulated virtual screening evaluation were then performed
      to verify the reliability and discriminating ability of the pharmacophore.
      Meanwhile, the homology model of CB(1) receptor was constructed based on the
      crystal structure of human beta (2) adrenergic receptor (beta (2)-AR). Several
      classical antagonists were then docked into the optimized homology model with
      induced fit docking method. A hydrogen bond between the antagonists and Lys192 on
      the third transmembrane helix of the receptor was formed in the docking study,
      which has proven to be critical for receptor-ligand interaction by biological
      experiments. The structure obtained from induced fit docking was then confirmed
      to be a reliable model for molecular docking from the result of the simulated
      virtual screening. The consistency between the pharmacophore and the homology
      structure further proved the previous observation. The built receptor structure
      and antagonists' pharmacophore should be useful for the understanding of
      inhibitory mechanism and development of novel CB(1) antagonists.

PMID- 22402755
TI  - Public preferences regarding the return of individual genetic research results:
      findings from a qualitative focus group study.
AB  - PURPOSE: People are interested in receiving their individual research results in
      exchange for participating in genetic research. However, it is unclear whether
      the public understands the nature and limitations of these results and whether
      they would want information with unknown clinical utility. METHODS: We conducted
      10 focus groups in three US cities to examine the types of results people would
      want and the perceived value of different types of individual research results.
      RESULTS: Nearly all focus group participants said they would want at least some
      individual research results returned. Priority was placed on results that are
      well understood. Less important to participants were the magnitude of the risk
      conferred and actionability of the result. In addition to helping treat or
      prevent disease, participants identified several other potential health-related
      and personal reasons for wanting individual research results. Many believed that
      researchers have an obligation to return individual research results. Although
      most people would prefer to receive as much information as possible, many would
      accept the return of a limited set of results. CONCLUSION: Participants
      understood the nuances and limitations of individual research results.
      Researchers deciding the value of returning a given result should consider using
      a broader definition of clinical utility as well as the possible personal utility
      of the information.

PMID- 22402756
TI  - Performance of PREMM(1,2,6), MMRpredict, and MMRpro in detecting Lynch syndrome
      among endometrial cancer cases.
AB  - PURPOSE: Lynch syndrome accounts for 2-5% of endometrial cancer cases. Lynch
      syndrome prediction models have not been evaluated among endometrial cancer
      cases. METHODS: Area under the receiver operating curve (AUC), sensitivity and
      specificity of PREMM(1,2,6), MMRpredict, and MMRpro scores were assessed among
      563 population-based and 129 clinic-based endometrial cancer cases. RESULTS: A
      total of 14 (3%) population-based and 80 (62%) clinic-based subjects had
      pathogenic mutations. PREMM(1,2,6), MMRpredict, and MMRpro were able to
      distinguish mutation carriers from noncarriers (AUC of 0.77, 0.76, and 0.77,
      respectively), among population-based cases. All three models had lower
      discrimination for the clinic-based cohort, with AUCs of 0.67, 0.64, and 0.54,
      respectively. Using a 5% cutoff, sensitivity and specificity were as follows:
      PREMM(1,2,6), 93% and 5% among population-based cases and 99% and 2% among clinic
      based cases; MMRpredict, 71% and 64% for the population-based cohort and 91% and
      0% for the clinic-based cohort; and MMRpro, 57% and 85% among population-based
      cases and 95% and 10% among clinic-based cases. CONCLUSION: Currently available
      prediction models have limited clinical utility in determining which patients
      with endometrial cancer should undergo genetic testing for Lynch syndrome.
      Immunohistochemical analysis and microsatellite instability testing may be the
      best currently available tools to screen for Lynch syndrome in endometrial cancer
      patients.

PMID- 22402757
TI  - An integrated approach for classifying mitochondrial DNA variants: one clinical
      diagnostic laboratory's experience.
AB  - PURPOSE: The mitochondrial genome is highly polymorphic. A unique feature of
      deleterious mitochondrial DNA (mtDNA) mutations is heteroplasmy. Genetic
      background and variable penetrance also play roles in the pathogenicity for a
      mtDNA variant. Clinicians are increasingly interested in requesting mtDNA
      testing. However, interpretation of uncharacterized mtDNA variants is a great
      challenge. We suggest a stepwise interpretation procedure for clinical service.
      METHODS: We describe the algorithms used to interpret novel and rare mtDNA
      variants. mtDNA databases and in silico predictive algorithms are used to
      evaluate the pathogenic potential of novel and/or rare mtDNA variants. RESULTS:
      mtDNA variants can be classified into three categories: benign variants,
      unclassified variants, and deleterious mutations based on database search and in
      silico prediction. Targeted DNA sequence analysis of matrilineal relatives,
      heteroplasmy quantification, and functional studies are useful to classify mtDNA
      variants. CONCLUSION: Clinical significance of a novel or rare variant is
      critical in the diagnosis of the disease and counseling of the family. Based on
      the results from clinical, biochemical, and molecular genetic studies of multiple
      family members, proper interpretation of mtDNA variants is important for clinical
      laboratories and for patient care.

PMID- 22402758
TI  - Taking aims seriously: repository research and limits on the duty to return
      individual research findings.
AB  - Most discussions of researchers' duties to return incidental findings or research
      results to research participants or repository contributors fail to provide an
      adequate theoretical grounding for such duties. Returning findings is a positive
      duty, a duty to help somebody. Typically, such duties are specified narrowly such
      that helping is only a duty when it poses little or no risk or burden to the
      helper and does not interfere with her legitimate aims. Under current budgetary
      and personnel constraints, and with currently available information technology,
      routine return of individual findings from research using repository materials
      would constitute a substantial burden on the scientific enterprise and would
      seriously frustrate the aims of both scientists and specimen/data contributors.
      In most cases, researchers' limited duties to help repository contributors
      probably can be fulfilled by some action less demanding than returning individual
      findings. Furthermore, the duty-to-return issue should be analyzed as a conflict
      between (possibly) helping some contributors now and (possibly) helping a greater
      number of people who would benefit in the future from the knowledge produced by
      research.

PMID- 22402759
TI  - PET bottle use patterns and antimony migration into bottled water and soft
      drinks: the case of British and Nigerian bottles.
AB  - While antimony has been reported to migrate from PET bottles into contents,
      reports on bottled water and soft drinks usage and PET bottle reuse patterns are
      currently unavailable in the literature. Bottle use conditions and patterns are
      important determinants of antimony migration. In this work a survey assessing the
      pattern of bottle use and reuse in Britain and Nigeria was undertaken. The survey
      findings influenced the design of laboratory experiments that assessed the
      migration of antimony from PET bottles into water and soft drinks. Typical
      storage durations for bottled contents between purchase and opening for use were
      7 days or less. However storage of up to one year was reported. Bottle reuse was
      high and similar for the two countries with reuse durations being higher in
      Nigeria. The antimony concentration in 32 PET bottle materials from Britain and
      Nigeria were similar and ranged between 177 and 310 mg kg(-1). For 47 freshly
      purchased British bottled contents antimony concentration ranged between 0.03 and
      6.61 MUg L(-1) with only one sample exceeding the EU acceptable limit.
      Concentrations of Cd, Ge, Zn, Al, Be, Ti, Co and Pb were also measured. At
      realistic temperatures of 40 and 60  degrees C antimony concentration in
      deionised water in bottles remained below the EU acceptable limit even after 48 h
      exposure. The limit was exceeded for most exposures at 80  degrees C.
      Concentration of antimony in some bottled contents exceeded the EU limit after 11
      months of storage at room temperature. Bottle aging and increase in bottle volume
      were associated with decreased migration of antimony from bottles.

PMID- 22402760
TI  - Musculoskeletal ultrasonography in physical and rehabilitation medicine.
AB  - Musculoskeletal ultrasound has gained a significant place in the diagnosis and
      management of various musculoskeletal disorders due to its several advantages
      (being convenient, inexpensive, non-invasive, repeatable, providing dynamic
      imaging and not requiring any exposure to radiation). It has also become a
      valuable tool in the daily clinical practice of physical and rehabilitation
      medicine physicians; the musculoskeletal ultrasound probe having become
      synonymous with the physician's stethoscope. In this paper, aside from drawing
      attention to this growing issue in the agenda of PRM physicians, we will touch
      upon its basic technical features and certain aspects as regards muscle, tendon,
      ligament, nerve, joint lesions and ultrasound guided interventions.

PMID- 22402762
TI  - Resistance to mericitabine, a nucleoside analogue inhibitor of HCV RNA-dependent
      RNA polymerase.
AB  - Mericitabine (RG7128), an orally administered prodrug of PSI-6130, is the most
      clinically advanced nucleoside analogue inhibitor of the RNA-dependent RNA
      polymerase (RdRp) of HCV. This review describes what has been learnt so far about
      the resistance profile of mericitabine. A serine to threonine substitution at
      position 282 (S282T) of the RdRp that reduces its replication capacity to
      approximately 15% of wild-type is the only variant that has been consistently
      generated in serial in vitro passage experiments. To date, no evidence of
      genotypic resistance to mericitabine has been detected by population or clonal
      sequence analysis in any baseline or on-treatment samples collected from >600
      patients enrolled in Phase I/II trials of mericitabine administered as
      monotherapy, in combination with pegylated interferon/ribavirin, or in
      combination with the protease inhibitor, danoprevir, for 14 days in the proof-of
      concept study of interferon-free therapy.

PMID- 22402763
TI  - Update of spectroscopic data for 4-hydroxydictyolactone and dictyol E isolated
      from a Halimeda stuposa - Dictyota sp. assemblage.
AB  - The methanol extract of an assemblage of Halimeda stuposa and a Dictyota sp.,
      yielded three natural products characteristic of Dictyota sp., and one of
      Halimeda sp. These included the xenicane diterpene 4-hydroxydictyolactone (1),
      and the diterpenes dictyol E (2), 8a,11-dihydroxypachydictyol A (3) and indole-3
      carboxaldehyde (4). A minor revision of 1 and new spectroscopic data for 1 and 2
      are provided, along with associated anti-cancer activities of compounds.

PMID- 22402764
TI  - alpha-Mangostin enhances betulinic acid cytotoxicity and inhibits cisplatin
      cytotoxicity on HCT 116 colorectal carcinoma cells.
AB  - Despite the progress in colon cancer treatment, relapse is still a major
      obstacle. Hence, new drugs or drug combinations are required in the battle
      against colon cancer. alpha-Mangostin and betulinic acid (BA) are cytotoxic
      compounds that work by inducing the mitochondrial apoptosis pathway, and
      cisplatin is one of the most potent broad spectrum anti-tumor agents. This study
      aims to investigate the enhancement of BA cytotoxicity by alpha-mangostin, and
      the cytoprotection effect of alpha-mangostin and BA on cisplatin-induced
      cytotoxicity on HCT 116 human colorectal carcinoma cells. Cytotoxicity was
      investigated by the XTT cell proliferation test, and the apoptotic effects were
      investigated on early and late markers including caspases-3/7, mitochondrial
      membrane potential, cytoplasmic shrinkage, and chromatin condensation. The effect
      of alpha-mangostin on four signalling pathways was also investigated by the
      luciferase assay. alpha-Mangostin and BA were more cytotoxic to the colon cancer
      cells than to the normal colonic cells, and both compounds showed a
      cytoprotective effect against cisplatin-induced cytotoxicity. On the other hand,
      alpha-mangostin enhanced the cytotoxic and apoptotic effects of BA. Combination
      therapy hits multiple targets, which may improve the overall response to the
      treatment, and may reduce the likelihood of developing drug resistance by the
      tumor cells. Therefore, alpha-mangostin and BA may provide a novel combination
      for the treatment of colorectal carcinoma. The cytoprotective effect of the
      compounds against cisplatin-induced cytotoxicity may find applications as
      chemopreventive agents against carcinogens, irradiation and oxidative stress, or
      to neutralize cisplatin side effects.

PMID- 22402765
TI  - Solvothermal synthesis of Pt-Pd alloys with selective shapes and their enhanced
      electrocatalytic activities.
AB  - Pt-Pd bimetallic alloy nanostructures with highly selective morphologies such as
      cube, bar, flower, concave cube, and dendrite have been achieved through a facile
      one-pot solvothermal synthesis. The effects of shape-controllers (sodium dodecyl
      sulfate (SDS), ethylenediamine-tetraacetic acid disodium salt (EDTA-2Na), NaI)
      and solvents (water/DMF) on the morphologies were systematically investigated.
      The electrocatalytic activities of these Pt-Pd alloy nanostructures toward formic
      acid oxidation were tested. The results indicated that these alloy nanocrystals
      exhibited enhanced and shape-dependent electrocatalytic activity toward formic
      acid oxidation compared to commercial Pt black and Pt/C catalysts.

PMID- 22402768
TI  - Proprioception 3 years after shoulder arthroplasty in 3D motion analysis: a
      prospective study.
AB  - BACKGROUND: This prospective study evaluated the development of proprioception
      over the course of 3 years after shoulder arthroplasty. METHODS: Twenty-one
      patients were enrolled who underwent total shoulder arthroplasty (n = 10) or
      hemiarthroplasty (HEMI) (n = 11) for shoulder osteoarthritis. All patients were
      examined 1 day before the operation, 6 months and 3 years after surgery in a
      motion analysis study with an active angle-reproduction (AAR) test. RESULTS:
      Overall proprioception measured by the AAR deteriorated significantly 3 years
      after surgery [from 6.6 degrees  (SD 3.1) to 10.3 degrees  (SD 5.7); p = 0.017]
      and was significantly worse than in the control group [10.3 degrees  (SD 5.7) vs.
      7.8 degrees  (SD 2.3); p = 0.030). In the HEMI subgroup, 3 years after shoulder
      replacement, there is a significant deterioration of proprioception at 30 degrees
      of external rotation [from 3.1 degrees  (SD 3.5) to 12.8 degrees  (SD 10.7); p =
      0.031]. On average, in the TSA subgroup proprioception deteriorated from 7.1
      degrees  (SD 3.1) to 8.6 degrees  (SD 1.4) and in the HEMI subgroup from 6.1
      degrees  (SD 2.1) to 12.4 degrees  (SD 8.3). The comparison of postoperative
      impairment of proprioception between the TSA and HEMI subgroup showed
      significantly worse proprioception for the HEMI subgroup at 30 degrees  of
      external rotation [9.8 degrees  (SD 10.1) vs. 1.6 degrees  (SD 6.3) in the TSA
      group; p = 0.046]. CONCLUSION: In conclusion, proprioception that was measured by
      an AAR test remained unchanged or deteriorated 3 years after shoulder
      arthroplasty. The postoperative deterioration of proprioception was more
      distinctive in HEMI than in TSA group.

PMID- 22402769
TI  - Functional and clinical outcome of total shoulder arthroplasty with oversized
      glenoid.
AB  - BACKGROUND: The Epoca-Reconstruction-(Reco)(r)-Glenoid has been developed to
      treat patients with cuff-tear-arthropathy. The glenoid component of this system
      has a hemispheric shape that canopies the humeral head. This design is believed
      to provide a stable fulcrum and restore normal deltoid function. The purpose of
      this study was to analyse strengths and disadvantages of the Epoca-Reco(r)
      Glenoid in cuff-tear-arthropathy patients. Changes in functional outcome using
      Constant-Murley-Scoring(CMS), CMS sub-scoring parameters and radiological outcome
      were analysed. For this purpose, a classification for radiologic lucency was
      proposed. Diverging results, influencing factors and alternative treatment
      options have been discussed to analyse weaknesses and enhance future development
      of this arthroplastic model. MATERIALS AND METHODS: 23 patients aged 68 +/- 8.4
      years with irreparable cuff-tear-arthropathy refractory to physiotherapeutic
      treatment were treated with Reco-Glenoid Total-Shoulder-Arthroplasty (TSA). Pre
      operative standardized evaluations included history, physical examination,
      radiographs, computer tomography and clinical scorings. The post-operative
      controls included physical examination with CMS, video documentation and
      radiological evaluation. RESULTS: After a median follow-up time of 38 +/- 18
      months, the CMS had been significantly improved (p < 0.001) from (17.4 +/- 5.8)
      to (43.2 +/- 19.2) points. Significant improvement in pain, activities of daily
      life, range of motion (p < 0.001) and power (p = 0.006) was achieved.
      Significantly, inferior results in functional outcome and higher lucency rates
      were observed in female patients and in patients treated with small glenoid
      components. The follow-up rate was 100 %. CONCLUSION: The semi-constraint
      reconstruction glenoid prosthesis model in cuff-tear-arthropathy patients
      significantly improves shoulder function, however, it yields controversial
      results, with satisfactory results in male and poor results in female patients.
      Revision rate of the female cohort and loosening of the glenoid component in this
      short-term follow-up is of concern. Further investigations taking BMD, osteopenic
      conditions and influence of surface area in smaller individuals into
      consideration are recommended, to determine whether this is the underlying cause
      of the inferior results in females.

PMID- 22402770
TI  - Double stranded polymeric ladderphanes with 16-pi-electron antiaromatic
      metallocycle linkers.
AB  - Three double stranded polymeric ladderphanes with 16-pi-electron antiaromatic
      metallocycle linkers are synthesised by ring opening metathesis polymerisation of
      the corresponding bisnorbornene monomers. Scanning tunnelling microscopic (STM)
      images indicate that these polymers can assemble nicely on a graphite surface to
      form a highly ordered pattern which has been observed in other ladderphanes with
      different kinds of aromatic linkers. Little change in (1)H NMR, absorption
      spectra and electrochemical oxidation potential between these polymers and the
      corresponding monomers suggest that there would be no interactions between
      adjacent antiaromatic linkers in these polymeric ladderphanes. Presumably, the
      distance between two antiaromatic rings in these ladderphanes (5-6 A) is far too
      long in comparison with that between two rings in methylene-bridged antiaromatic
      superphanes (2.5 A<), where stabilisation is predicted by theoretical
      calculations.

PMID- 22402771
TI  - Evidence for scent marking in vervet monkeys?
AB  - We used data from two troops of free-ranging vervet monkeys (Chlorocebus
      aethiops) to assess the proposition that the conspicuous chest rubbing observed
      in this species constitutes scent-marking behavior. Our data indicate that chest
      rubbing behavior is associated with higher-ranking males who are more likely to
      do so during the breeding season in areas where territorial encounters occur. We
      found no indication that chest rubbing was triggered directly by encounters
      between troops. We conclude that these data, in conjunction with reports of chest
      rubbing from other Old World monkeys, are sufficiently suggestive of scent
      marking to warrant further, directed research and support the suspicion that
      olfactory cues remain important to catarrhines in a number of domains.

PMID- 22402772
TI  - Algorithm to determine the outcome of patients with acute liver failure: a data
      mining analysis using decision trees.
AB  - BACKGROUND: We established algorithms to predict the prognosis of acute liver
      failure (ALF) patients through a data-mining analysis, in order to improve the
      indication criteria for liver transplantation. METHODS: The subjects were 1,022
      ALF patients seen between 1998 and 2007 and enrolled in a nationwide survey.
      Patients older than 65 years, and those who had undergone liver transplantation
      and received blood products before the onset of hepatic encephalopathy were
      excluded. Two data sets were used: patients seen between 1998 and 2003 (n=698),
      whose data were used for the formation of the algorithm, and those seen between
      2004 and 2007 (n=324), whose data were used for the validation of the algorithm.
      Data on a total of 73 items, at the onset of encephalopathy and 5 days later,
      were collected from 371 of the 698 patients seen between 1998 and 2003, and their
      outcome was analyzed to establish decision trees. The obtained algorithm was
      validated using the data of 160 of the 324 patients seen between 2004 and 2007.
      RESULTS: The outcome of the patients at the onset of encephalopathy was predicted
      through 5 items, and the patients were classified into 6 categories with
      mortality rates between 23% and89%. When the prognosis of the patients in the
      categories with mortality rates greater than 50% was predicted as "death", the
      accuracy, sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) of the algorithm were 79, 78, 81, 83, and 75%,
      respectively. Similar high values were obtained when the algorithm was employed
      in the patients for validation. The outcome of the patients 5 days after the
      onset of encephalopathy was predicted through 7 items, and a similar high
      accuracy was found for both sets of patients. CONCLUSIONS: Novel algorithms for
      predicting the outcome of ALF patients may be useful to determine the indication
      for liver transplantation.

PMID- 22402773
TI  - Portal hemodynamic effects of sorafenib in patients with advanced hepatocellular
      carcinoma: a prospective cohort study.
AB  - BACKGROUND AND AIMS: Sorafenib is currently in clinical use as an oral
      multikinase inhibitor that blocks tumor growth and cell proliferation in advanced
      hepatocellular carcinoma (HCC). It has been demonstrated in a translating study
      that sorafenib had a beneficial effect on portocollateral circulation in
      cirrhotic animals with portal hypertension. This study was prospectively
      performed to evaluate the portal hemodynamic effect of sorafenib in patients with
      advanced HCC using duplex Doppler ultrasonography (DDU). METHODS: Twenty-five
      Child-Pugh class-A patients with advanced HCC had received sorafenib at a dose of
      400 mg twice daily. Primary outcomes were changes in portal venous area (PVA;
      cm(2)) as seen by using DDU before and after a 2-week administration of
      sorafenib. Secondary outcomes included the changes of laboratory data and other
      flow data revealed on DDU. RESULTS: PVA was significantly decreased after a 2
      week administration (0.78 +/- 0.23 vs. 0.64 +/- 0.25, P = 0.023), while the
      portal venous flow velocity (PVV; cm/s) was not significantly changed (0.22 +/-
      0.06 vs. 0.24 +/- 0.07, P = 0.17). Therefore, the congestion index (PVA/PVV),
      which reflects the pathophysiological hemodynamics of portal venous system, was
      significantly decreased (3.9 +/- 1.7 vs. 3.0 +/- 1.4, P = 0.042). CONCLUSIONS: We
      demonstrated the portal hemodynamic effect of sorafenib in patients with advanced
      HCC. Considering that this was a short-term study, because sorafenib could be a
      potential beneficial therapeutic agent for portal hypertension, it will be
      necessary to verify its clinical benefits for portal hypertension in future
      studies.

PMID- 22402774
TI  - Attenuation of indomethacin-induced gastric mucosal injury by prophylactic
      administration of sake yeast-derived thioredoxin.
AB  - BACKGROUND: Indomethacin is one of the group of nonsteroidal anti-inflammatory
      drugs, which often cause gastric mucosal injury as a side effect. Infiltration
      and activation of inflammatory cells, production of proinflammatory cytokines and
      chemokines, generation of reactive oxygen species, and activation of apoptotic
      signaling are involved in the pathogenesis of indomethacin-induced gastric
      injury. We examined whether sake yeast-derived thioredoxin (a small redox-active
      protein with anti-oxidative activity and various redox-regulating functions)
      reduced indomethacin-induced gastric injury. METHODS: Gastric injury was produced
      by the intraperitoneal administration of indomethacin (40 mg/kg body weight) to
      C57BL/6 mice. Prior to the administration of indomethacin, the mice were offered
      food pellets containing non-genetically modified sake yeast-derived thioredoxin
      (thioredoxin 200 MUg/g) for 3 days. Histological examinations, assessment of
      myeloperoxidase activity, and analysis of the gene expressions of proinflammatory
      cytokines and a chemokine (interleukin [IL]-1beta, IL-6, and CXCL1) were
      statistically evaluated. Indomethacin cytotoxicity was determined by lactate
      dehydrogenase release from murine gastric epithelial GSM06 cells induced by 24-h
      treatment with 200 and 400 MUM indomethacin after 1-h preincubation with 100
      MUg/ml sake yeast-derived thioredoxin. RESULTS: Macroscopic (edema, hemorrhage,
      and ulcers) and histological (necrosis, submucosal edema, neutrophil
      infiltration) findings induced by indomethacin were significantly reduced by
      pretreatment with food pellets containing thioredoxin. Gastric myeloperoxidase
      activity and the gene expressions of proinflammatory cytokines (IL-1beta and IL
      6) were also significantly reduced by this pretreatment compared with findings in
      the mice not pretreated with thioredoxin-containing food pellets. The
      administration of sake yeast-derived thioredoxin significantly reduced
      indomethacin-induced cytotoxicity in GSM06 cells. CONCLUSIONS: We conclude that
      oral administration of sake yeast-derived thioredoxin reduces indomethacin
      induced gastric injury. Sake yeast-derived thioredoxin may have therapeutic
      potential against indomethacin-induced gastric injury.

PMID- 22402776
TI  - Further evidence for addition and numerical competence by a Grey parrot
      (Psittacus erithacus).
AB  - A Grey parrot (Psittacus erithacus), able to quantify sets of eight or fewer
      items (including heterogeneous subsets), to sum two sequentially presented sets
      of 0-6 items (up to 6), and to identify and serially order Arabic numerals (1-8),
      all by using English labels (Pepperberg in J Comp Psychol 108:36-44, 1994; J
      CompPsychol 120:1-11, 2006a; J Comp Psychol 120:205-216,2006b; Pepperberg and
      Carey submitted), was tested on addition of two Arabic numerals or three
      sequentially presented collections (e.g., of variously sized jelly beans or
      nuts). He was, without explicit training and in the absence of the previously
      viewed addends, asked, "How many total?" and required to answer with a vocal
      English number label. In a few trials on the Arabic numeral addition, he was also
      shown variously colored Arabic numerals while the addends were hidden and asked
      "What color number (is the) total?" Although his death precluded testing on all
      possible arrays, his accuracy was statistically significant and suggested
      addition abilities comparable with those of nonhuman primates.

PMID- 22402775
TI  - Clinical aspect and molecular mechanism of DNA aneuploidy in gastric cancers.
AB  - The biological characteristics of cancers depend mostly on genetic alterations in
      the cancer cells of individuals. Gastric cancers show a high frequency of DNA
      aneuploidy, a phenotype of chromosomal instability. Compared to diploid tumors,
      gastric carcinomas with aneuploidy have been shown to have high proliferative
      activity and high metastatic or invasive potential; these characteristics lead to
      a poor prognosis. It has been suggested that an abnormal spindle assembly
      checkpoint is involved in DNA aneuploidy, but the underlying mechanism is still
      unclear. This review, in order to determine whether gastric carcinomas that
      display aneuploidy are associated with a poorer prognosis than diploid tumors,
      and to discuss the biological mechanisms that induce aneuploidy, summarizes the
      results of studies on DNA ploidy in gastric cancer published in the English
      literature. Analysis of DNA ploidy in gastric cancer may provide clinically
      useful information from diagnostic, therapeutic, and prognostic standpoints.
      Further investigations may be needed to clarify the relationship between
      chromosome instability and DNA ploidy.

PMID- 22402777
TI  - The confusing world of dietary sugars: definitions, intakes, food sources and
      international dietary recommendations.
AB  - Government and health organizations worldwide have issued dietary guidelines for
      sugars. These guidelines vary considerably in the recommended or suggested
      intakes and the types of sugars specified. Despite access to the same published
      literature, recommendations vary greatly and create confusion for nutrition
      practitioners who offer dietary guidance. Some of the confusion in this field is
      linked to differences in definitions for sugar and methods to measure total
      sugars. Additionally, although dietary guidance typically recommends foods high
      in sugar, fruits and dairy products, other advice suggests strict limits on
      intake of "added sugar". Added sugar cannot be analytically determined and must
      be calculated so nutrient databases generally contain values for total sugar and
      do not differentiate between sugars naturally occurring in foods and those added
      in processing. This review defines sugars, provides the sugar content of major
      food sources, summarizes health concerns about dietary sugars, and compiles
      dietary guidelines for sugars issued by various organizations. Dietary
      recommendations from various health organizations are based on different means of
      assessment, and thus vary considerably. In general, the use of added sugars is
      cautioned, especially when it contributes to calories in excess of needs for an
      individual.

PMID- 22402778
TI  - Laboratory toxicity and benthic invertebrate field colonization of Upper Columbia
      River sediments: finding adverse effects using multiple lines of evidence.
AB  - From 1930 to 1995, the Upper Columbia River (UCR) of northeast Washington State
      received approximately 12 million metric tons of smelter slag and associated
      effluents from a large smelter facility located in Trail, British Columbia,
      approximately 10 km north of the United States-Canadian border. Studies conducted
      during the past two decades have demonstrated the presence of toxic
      concentrations of heavy metals in slag-based sandy sediments, including cadmium,
      copper, zinc, and lead in the UCR area as well as the downstream reservoir
      portion of Lake Roosevelt. We conducted standardized whole-sediment toxicity
      tests with the amphipod Hyalella azteca (28-day) and the midge Chironomus dilutus
      (10-day) on 11 samples, including both UCR and study-specific reference
      sediments. Metal concentrations in sediments were modeled for potential toxicity
      using three approaches: (1) probable effects quotients (PEQs) based on total
      recoverable metals (TRMs) and simultaneously extracted metals (SEMs); (2) SEMs
      corrected for acid-volatile sulfides (AVS; i.e., ?SEM - AVS); and (3) ?SEM - AVS
      normalized to the fractional organic carbon (f(oc)) (i.e., ?SEM - AVS/f(oc)). The
      most highly metal-contaminated sample (?PEQ(TRM) = 132; ?PEQ(SEM) = 54; ?SEM -
      AVS = 323; and ?SEM - AVS/(foc) = 64,600 umol/g) from the UCR was dominated by
      weathered slag sediment particles and resulted in 80% mortality and 94% decrease
      in biomass of amphipods; in addition, this sample significantly decreased growth
      of midge by 10%. The traditional ?AVS - SEM, uncorrected for organic carbon, was
      the most accurate approach for estimating the effects of metals in the UCR.
      Treatment of the toxic slag sediment with 20% Resinex SIR-300 metal-chelating
      resin significantly decreased the toxicity of the sample. Samples ?SEM - AVS >
      244 was not toxic to amphipods or midge in laboratory testing, indicating that
      this value may be an approximate threshold for effects in the UCR. In situ
      benthic invertebrate colonization studies in an experimental pond (8-week
      duration) indicated that two of the most metal-contaminated UCR sediments
      (dominated by high levels of sand-sized slag particles) exhibited decreased
      invertebrate colonization compared with sand-based reference sediments. Field
      exposed SIR-300 resin samples also exhibited decreased invertebrate colonization
      numbers compared with reference materials, which may indicate behavioral
      avoidance of this material under field conditions. Multiple lines of evidence
      (analytical chemistry, laboratory toxicity, and field colonization results),
      along with findings from previous studies, indicate that high metal
      concentrations associated with slag-enriched sediments in the UCR are likely to
      adversely impact the growth and survival of native benthic invertebrate
      communities. Additional laboratory toxicity testing, refinement of the
      applications of sediment benchmarks for metal toxicity, and in situ benthic
      invertebrate studies will assist in better defining the spatial extent, temporal
      variations, and ecological impacts of metal-contaminated sediments in the UCR
      system.

PMID- 22402779
TI  - Polybrominated diphenyl ether contamination in soil, vegetation, and cow milk
      from a high-mountain pasture in the Italian Alps.
AB  - This study investigates contamination by 13 polybrominated diphenyl ether (PBDE)
      congeners in a high-mountain pasture located in the Italian Alps. The trend of
      PBDE contamination in three soil layers was investigated by a spring-summer
      sampling period to understand the importance of different environmental
      variables, such as seasonality, topographical aspect, and soil features. We also
      evaluated PBDE accumulation in grasses covering the plateau, and because the
      study area has been used for a pasture for a long time, we measured PBDE levels
      in milk from grazing cows. Overall, we found moderate PBDE contamination in
      Andossi soils, with differences depending on the layer, mountain side, and
      organic matter content. The vegetation of the plateau had greater PBDE
      concentrations than the soils and showed a grass/soil accumulation ratio between
      2 and 12, indicating that deposition from the atmosphere is actually the dominant
      process in this area. Last, PBDE concentrations in milk followed similar seasonal
      trends as the vegetation but showed variations in congener abundance in agreement
      with the biotransformation susceptibility, absorption efficiency, and residence
      time of different BDEs in dairy cattle.

PMID- 22402780
TI  - National screening study on 10 perfluorinated compounds in raw and treated tap
      water in France.
AB  - The occurrence of seven perfluoroalkyl carboxylates (PFCAs) and three
      perfluoroalkyl sulfonates (PFASs) was studied in raw- and treated-water samples
      from public water systems. Two sampling campaigns were performed during the
      summer of 2009 and in June 2010. Sampling was equally distributed across the 100
      French departments. In total, 331 raw-water samples and 110 treated-water samples
      were analyzed during this study, representing approximately 20% of the national
      water supply flow. Concentrations of perfluorinated compounds (PFCs) were
      determined using automated solid-phase extraction and liquid chromatography
      tandem mass spectrometry. In raw-water samples, the highest individual PFC
      concentration was 139 ng/L for perfluorohexanoic acid (PFHxA). The sum of all of
      the determined components was >100 ng/L at three sampling points (199, 117, and
      115 ng/L). Of the investigated PFCs, perfluorooctane sulfonate (PFOS),
      perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), and PFHxA
      predominated (detected in 27%, 13%, 11%, and 7% of samples, respectively).
      Geographical variability was observed, with departments crossed by major rivers
      or with high population densities being more affected by PFC contamination.
      Compared with raw water, short-chain PFCAs, but not PFASs, were found in higher
      abundance in treated water. This difference suggests a relative effectiveness of
      certain water treatments for the elimination of PFASs but also a possible
      degradation of PFCA precursors by water-treatment processes. Our investigations
      did not show any heavily contaminated sites. In treated-water samples, the
      highest individual PFC concentration was 125 ng/L for PFHxA. The sum of all of
      the determined components was >100 ng/L at one sampling point (156 ng/L). The
      values observed for PFOS and PFOA in drinking water were not greater than the
      health-based drinking-water concentration protectives for lifetime exposure that
      have been defined for other countries.

PMID- 22402781
TI  - Metal accumulation from dietary exposure in the sea urchin, Strongylocentrotus
      droebachiensis.
AB  - Metal contamination is a common problem in aquatic environments and may result in
      metal bioaccumulation and toxicity in aquatic biota. Recent studies have reported
      the significance of dietary metal accumulation in aquatic food chains,
      particularly in species of lower trophic levels. This research investigated the
      accumulation and effects of dietary metals in a macroinvertebrate. The seaweed
      species Ulva lactuca and Enteromorpha prolifera were concurrently exposed to five
      metals (copper, nickel, lead, cadmium, and zinc) and then individually fed to the
      green sea urchin Strongylocentrotus droebachiensis for a period of 2 weeks. Body
      mass, test length, total length, and coelomic fluid ion concentration and
      osmolality were measured. The sea urchins were also dissected and their organs
      (esophagus, stomach, intestine, gonads, and rectum) digested and analyzed for
      metals. The results demonstrated that metal accumulation and distribution varied
      between seaweed species and among metals. In general, there were greater
      concentrations of metals within the sea urchins fed E. prolifera compared with
      those fed U. lactuca. All of the metals accumulated within at least one organ of
      S. droebachiensis, with Cu being most significant. These results indicate that E.
      prolifera may accumulate metals in a more bioavailable form than within U.
      lactuca, which could impact the grazer. In this study, no significant differences
      in body length, growth, or coelomic fluid ion concentration and osmolality were
      detected between the control and metal-exposed sea urchins after the 2-week
      testing period. This research presents new data concerning metal accumulation in
      a marine herbivore after dietary metal exposure.

PMID- 22402784
TI  - Probing the structural and electronic properties of small vanadium monoxide
      clusters.
AB  - The structural evolution and bonding of a series of early transition-metal oxide
      clusters, V(n)O(q) (n = 3-9, q = 0,-1), have been investigated with the aid of
      previous photoelectron spectroscopy (PES) and theoretical calculations. For each
      vanadium monoxide cluster, many low-lying isomers are generated using the
      Saunders "Kick" global minimum stochastic search method. Theoretical electron
      detachment energies (both vertical and adiabatic) were compared with the
      experimental measurements to verify the ground states of the vanadium monoxide
      clusters obtained from the DFT calculations. The results demonstrate that the
      combination of photoelectron spectroscopy experiments and DFT calculation is not
      only powerful for obtaining the electronic and atomic structures of size-selected
      clusters, but also valuable in resolving structurally and energetically close
      isomers. The second difference energies and adsorption energies as a function of
      the cluster size exhibit a pronounced even-odd alternation phenomenon. The
      adsorption energies of one O atom on the anionic (6.64 -> 8.16 eV) and neutral
      (6.41 -> 8.13 eV) host vanadium clusters are shown to be surprisingly high,
      suggesting strong capabilities to activate O by structural defects in vanadium
      oxides.

PMID- 22402783
TI  - AnatoMUS-I: ultrasonographic imaging of the peripheral nerves of the upper limb.

PMID- 22402785
TI  - Statin treatment for all individuals with cholesterol concentrations above
      "target"?: "Primum non nocere"--Hippocratic oath.

PMID- 22402786
TI  - High-pressure spin-crossover in a dinuclear Fe(II) complex.
AB  - The effect of pressure on the dinuclear spin crossover material
      [{Fe(bpp)(NCS)(2)}(2)(4,4'-bipy)].2MeOH (where bpp = 2,6-bis(pyrazol-3
      yl)pyridine and 4,4'-bipy = 4,4'-bipyridine, 1) has been investigated with single
      crystal X-ray diffraction and Raman spectroscopy using diamond anvil cell
      techniques. The very gradual pressure-induced spin crossover occurs between 7 and
      25 kbar, and shows no evidence of crystallographic phase transitions. The
      pressure-induced spin transition leads to a complete LS state which is not
      thermally accessible. This structural evolution under pressure is in stark
      contrast to the previously reported thermal spin crossover behaviour, in which a
      symmetry-breaking, purely structural phase transition results in only partial
      conversion to the low spin state. This observation is attributed to the symmetry
      breaking phase transition becoming unfavourable under pressure.

PMID- 22402787
TI  - Identifying core features of adaptive metabolic mechanisms for chronic heat
      stress attenuation contributing to systems robustness.
AB  - The contribution of metabolism to heat stress may play a significant role in
      defining robustness and recovery of systems; either by providing the energy and
      metabolites required for cellular homeostasis, or through the generation of
      protective osmolytes. However, the mechanisms by which heat stress attenuation
      could be adapted through metabolic processes as a stabilizing strategy against
      thermal stress are still largely unclear. We address this issue through
      metabolomic and transcriptomic profiles for populations along a thermal cline
      where two seagrass species, Zostera marina and Zostera noltii, were found in
      close proximity. Significant changes captured by these profile comparisons could
      be detected, with a larger response magnitude observed in northern populations to
      heat stress. Sucrose, fructose, and myo-inositol were identified to be the most
      responsive of the 29 analyzed organic metabolites. Many key enzymes in the Calvin
      cycle, glycolysis and pentose phosphate pathways also showed significant
      differential expression. The reported comparison suggests that adaptive
      mechanisms are involved through metabolic pathways to dampen the impacts of heat
      stress, and interactions between the metabolome and proteome should be further
      investigated in systems biology to understand robust design features against
      abiotic stress.

PMID- 22402788
TI  - Reproducibility and variability of global and regional dyssynchrony parameters
      derived from phase analysis of gated myocardial perfusion SPECT.
AB  - AIM: The aim of the study was to assess the reproducibility (R) and variability
      of quantitative parameters derived from Cedars-Sinai QGS software for phase
      analysis of G-SPECT in 39 coronary artery disease (CAD) patients with or without
      severe heart-failure (HF). METHODS: Phase standard deviation (s) and entropy (e)
      are global parameters that quantify dyssynchrony. Regional measures of
      dyssynchrony were also computed including differences between the lateral wall
      versus the septal wall (DmW) and differences between the averages of
      midventricular lateral versus midventricular septal segments (DmS). RESULTS:
      Global parameters e and s and regional parameters DmW and DmS exhibit excellent
      values of R=0.92, 0.99, 0.99 and 0.96, respectively. In regional parameters DmW
      and DmS there is a significant variability in individual scoring assessed by a
      standard error of measurement of =9.17 and 21.7, respectively. The box plots of e
      in patients with or without HF do not show any significant superimposition, while
      the box plots of s and DmW show a partial overlap mainly due to the significant
      variability of s and DmW within patients with HF. Conversely the box plots of DmS
      in patients with or without HF show a significant overlap due to the great
      variability of DmS within patients with HF. CONCLUSION: Regional parameters
      derived from phase analysis of G-SPECT studies are not useful in the individual
      assessment of dyssynchrony in CAD patients either due to large variability in
      individual scoring and to a large heterogeneity in HF patients. Global parameters
      (e and s) exhibit both an excellent reproducibility. Nonetheless, e seems to
      perform better than s in individual assessment of dyssynchrony due to a better
      separation between HF and non HF patients. Using the QGS software approach no
      manual intervention is necessary to ensure a good reproducibility of global
      parameters.

PMID- 22402790
TI  - Cranial hypertrophic pachymeningitis secondary to neurocysticercosis.
AB  - We report a case of a 46-year-old Brazilian woman, a farmer, who presented with
      recently uncontrolled epilepsy, daily headaches and ataxia. Cranial CT revealed
      hydrocephalus which was treated with ventricular drainage. Brain MRI revealed
      multiple parenchymal cysts of varying stages of neurocysticercosis. In addition,
      the patient presented with diffuse dural enhancement consisted with
      pachymeningitis, which is quite an unusual manifestation of neurocysticercosis.

PMID- 22402791
TI  - Chorea, convulsive seizures and cognitive impairment in a patient with autoimmune
      thyroid disease.

PMID- 22402792
TI  - Serum profile of pro- and anti-inflammatory cytokines in rats following
      implantation of low-temperature plasma-modified titanium plates.
AB  - Surface modification of Titanium (Ti) by low-temperature plasma influences cell
      material interactions. Therefore, this study aimed at examining serum cytokine
      levels and associations after intramuscular implantation (n = 8 rats/group) of Ti
      plates with Plasma Polymerized Allyl Amine (Ti-PPAAm), Plasma Polymerized Acrylic
      Acid (Ti-PPAAc), and without such layers (Ti-Controls). Pro-inflammatory (IL-2,
      IFNgamma, IL-6) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines were
      measured weekly for 56 days. Ti-PPAAm caused increased IL-2 (d7-14, d35),
      increased IFNgamma (d35) and decreased IL-10 (d35, d49-56). Ti-PPAAc induced
      divergent anti-inflammatory cytokine changes with increased IL-4 (d28-56) and
      decreased IL-10 (d42-56). Ti-Controls elicited increased IL-2 (d42) and IFNgamma
      (d35-42, d56). IL-6 was not detected and IL-13 only in three samples, thus they
      do not influence the response against these Ti implants. Correlation analysis
      revealed surface-dependent associations between cytokines indicating the
      involvement of different inflammatory cell populations. Concluding, different
      plasma modifications induce specific serum cytokine profiles and associations
      indicating distinct inflammatory responses.

PMID- 22402793
TI  - Availability of a 5% lidocaine patch used prophylactically for venipuncture- or
      injection-related pain in children.
AB  - PURPOSE: Venipuncture- or injection-related pain is still major problem during
      anesthetic induction in children. This study was designed to determine the
      availability of a 5% lidocaine patch used prophylactically for venipuncture- or
      injection-related pain during the induction of anesthesia. METHODS: In a
      randomized, double-blind study, 72 pediatric patients were allocated to one of
      two groups: pretreatment with a 5% lidocaine patch (Lidoderm((r)), Endo
      Pharmaceuticals, Chadds Ford, PA, USA) (group A) or pretreatment with a placebo
      patch (group B). Pain severity was evaluated on the Faces, Legs, Activity, Cry,
      and Consolability Scale (FLACC) during venipuncture, and a 4-point scale during
      the injection of rocuronium. RESULTS: The FLACC score during venipuncture was
      significantly lower for group A than group B (p < 0.001). There was no
      significant difference in the grades of the 4-point scale observed during the
      injection of rocuronium between groups A and B. No significant adverse effect was
      noted for the groups. CONCLUSION: Although pretreatment with a 5% lidocaine patch
      was found to be a safe, effective, and simple method of preventing venipuncture
      pain in children, this method did not reduce drug injection pain during the
      induction of anesthesia.

PMID- 22402794
TI  - Convergent diastereoselective preparation of adjacent quaternary stereocenters in
      an acyclic system.
AB  - The combined carbometalation-zinc homologation-allylation reaction of the
      resulting stereodefined 3,3-disubstituted allylmetal species with ketones allow
      the preparation of allylic vicinal diol derivatives in good yields with excellent
      diastereomeric ratios from commercially available alkynes. Two adjacent
      quaternary centers are formed with the concomitant formation of three new carbon
      carbon bonds in a single-pot operation in an acyclic system. The bulky
      substituent of the ketone occupies a pseudo-axial position in the Zimmerman
      Traxler transition state.

PMID- 22402795
TI  - Cell proliferation and oxidative stress pathways are modified in fibroblasts from
      Sturge-Weber syndrome patients.
AB  - Sturge-Weber syndrome (SWS) is defined by vascular malformations of the face, eye
      and brain and an underlying somatic mutation has been hypothesized. We employed
      isobaric tags for relative and absolute quantification (iTRAQ-8plex)-based liquid
      chromatography interfaced with tandem mass spectrometry (LC-MS/MS) approach to
      identify differentially expressed proteins between port-wine-derived and normal
      skin-derived fibroblasts of four individuals with SWS. Proteins were identified
      that were significantly up- or down-regulated (i.e., ratios >1.2 or <0.8) in two
      or three pairs of samples (n = 31/972 quantified proteins) and their associated p
      values reported. Ingenuity pathway analysis (IPA) tool showed that the up
      regulated proteins were associated with pathways that enhance cell proliferation;
      down-regulated proteins were associated with suppression of cell proliferation.
      The significant toxicologic list pathway in all four observations was oxidative
      stress mediated by Nrf2. This proteomics study highlights oxidative stress also
      consistent with a possible mutation in the RASA1 gene or pathway in SWS.

PMID- 22402796
TI  - Factors associated with severity of bovine tuberculosis in Ethiopian cattle.
AB  - Bovine TB is a disease of high economic and public health importance particularly
      in resource poor countries. Many aspects of pathogenesis of bovine TB in cattle
      have not been well understood. We carried out an investigation on 337 Ethiopian
      cattle with characteristic TB-like lesions to describe severity of pathology and
      factors associated with it. Severity of pathology was determined based upon gross
      lesion characteristics, distribution and presence/absence of viable mycobacteria.
      Molecular speciation of mycobacteria was performed using Gene-Probe's Accu-Probe
      method. Mycobacterium bovis was identified by genomic deletion analysis and
      spoligotyping. Data were analysed using descriptive statistics and regression
      model. The results showed that TB-like lesions and M. bovis were more frequently
      observed in lungs and respiratory lymph nodes. Mammary lesions yielded
      significant proportion of M. bovis upon culturing. Intestinal lesions were the
      second most frequently encountered pathology; upon culturing, however, the tissue
      specimens yielded the lowest proportion of M. bovis isolates. Sex, breed and
      management system were found to significantly affect TB manifestation. Female
      (beta +/- SE = 4.1 +/- 1.0; P = 0.00) and exotic breed (beta +/- SE = 1.7 +/-
      0.9; P = 0.045) were at a relatively higher risk of developing severe
      tuberculosis. TB pathology was more severe in cattle raised under large-scale
      farming (beta +/- SE = 2.3 +/- 0.5; P = 0.00). The fact that severe tuberculosis
      is linked to high degree of disease transmission potential warrants
      implementation of proper disease surveillance programs in large-scale farms.
      Isolation of M. bovis from mammary and muscle tissues implies a potential threat
      of zoonotic transmission, where raw milk and raw beef constitute a customary
      dietary regimen in Ethiopia.

PMID- 22402797
TI  - Susceptibility assay of Haemonchus contortus to commonly used anthelmintics in
      Jimma, southwest Ethiopia.
AB  - An experimental study to investigate the susceptibility pattern of Haemonchus
      contortus to commonly used anthelmintics (albendazole, tetramisole, ivermectin,
      and triclobendazole) was conducted between June and September 2009. Adult H.
      contortus parasites were collected from a total of 30 sheep slaughtered at Jimma
      municipal abattoir. The anthelmintics were assessed for egg hatch inhibition
      ability against H. contortus eggs. The eggs (500 eggs/ml) were incubated with
      different concentrations (0.25, 0.125, 0.0625, 0.03125, and 0.015625 MUg/ml) at
      26 degrees C for 48 h. Egg hatching inhibition of different anthelmintics at
      different concentrations was recorded. The overall mean percent inhibition showed
      that there was a significant difference (p < 0.05) among the different
      concentrations. Mean egg hatch inhibition of ivermectin showed the highest result
      (84.90 %) at 0.25 MUg/ml, followed by albendazole (78.77 %), triclobendazole
      (76.66 %), and tetramisole (78.98 %), respectively. The overall mean percent
      inhibition showed a significant difference (p < 0.05) among the different
      anthelmintics. Further evaluation of these anthelmintics was recommended.

PMID- 22402798
TI  - The gleam of the double-edged sword: the benefits of subgroups for organizational
      ethics.

PMID- 22402799
TI  - More than skin deep: visceral states are not projected onto dissimilar others.
AB  - What people feel shapes their perceptions of others. In the studies reported
      here, we examined the assimilative influence of visceral states on social
      judgment. Replicating prior research, we found that participants who were outside
      during winter overestimated the extent to which other people were bothered by
      cold (Study 1), and participants who ate salty snacks without water thought other
      people were overly bothered by thirst (Study 2). However, in both studies, this
      effect evaporated when participants believed that the other people under
      consideration held political views opposing their own. Participants who judged
      these dissimilar others were unaffected by their own strong visceral-drive
      states, a finding that highlights the power of dissimilarity in social judgment.
      Dissimilarity may thus represent a boundary condition for embodied cognition and
      inhibit an empathic understanding of shared out-group pain. Our findings reveal
      the need for a better understanding of how people's internal experiences
      influence their perceptions of the feelings and experiences of those who may hold
      values different from their own.

PMID- 22402800
TI  - Associations between TNFAIP3 gene polymorphisms and rheumatoid arthritis: a meta
      analysis.
AB  - OBJECTIVE: The aim of this study was to determine whether tumor necrosis factor
      alpha inducible protein 3 (TNFAIP3) polymorphisms confer susceptibility to
      rheumatoid arthritis (RA) in ethnically different populations. METHODS: The
      authors conducted meta-analyses on associations between the TNFAIP3 polymorphisms
      and RA susceptibility. RESULT: A total of ten comparative studies were included
      in this meta-analysis, which showed an association between the two allele of
      rs6920220 and RA in all study subjects [odds ratio (OR) 1.216, 95% confidence
      interval (CI) 1.166-1.269, p < 1.0 * 10(-9)]. The two allele of rs6920220 was
      also significantly associated with RA in Europeans only (OR 1.227, 95% CI 1.175
      1.282, p < 1.0 * 10(-9)). Meta-analysis revealed no association between the two
      allele of the rs10499194 polymorphism and RA in Europeans, but a significant
      association was found in Asians (OR 1.254, 95% CI 1.101-1.429, p=6.7 * 10(-4)).
      Furthermore, an association was found between the two allele of rs2230926 and RA
      in all study subjects (OR 1.390, 95% CI 1.214-2.331, p=1.9 * 10(-6)).
      CONCLUSIONS: This meta-analysis confirms that the TNFAIP3 polymorphisms are
      associated with RA susceptibility in different ethnic groups, namely, in
      Europeans for rs6920220 and in Asians for rs10499194.

PMID- 22402801
TI  - Improvement in kidney function: a real occurrence.

PMID- 22402802
TI  - Sources of drug coverage among Medicare beneficiaries with ESRD.
AB  - Despite extensive use of prescription medications in ESRD, relatively little is
      known about the participation of Medicare ESRD beneficiaries in the Part D
      program. Here, we quantitated the sources of drug coverage among ESRD
      beneficiaries and explored the Part D plan preferences of ESRD beneficiaries with
      regard to deductibles, coverage gaps, and monthly premiums. We obtained data on
      beneficiary sources of creditable coverage, characteristics of Part D plans,
      demographics, and residence from the Centers for Medicare and Medicaid Chronic
      Condition Data Warehouse and identified beneficiaries with ESRD from the US Renal
      Data System. We found that a substantial proportion (17.0%) of ESRD beneficiaries
      lacked a known source of creditable drug coverage in 2007 and 64.3% were enrolled
      in Part D. Of those enrolled, 72% received the Medicare Part D low-income
      subsidy. ESRD beneficiaries who enrolled in standalone Part D plans without the
      assistance of the low-income subsidy tended to prefer more comprehensive coverage
      options. In conclusion, more outreach is needed to ensure that beneficiaries who
      lack coverage obtain the coverage they need and that ESRD beneficiaries join the
      best plans for managing their disease and accompanying comorbid conditions.

PMID- 22402803
TI  - Kidney function can improve in patients with hypertensive CKD.
AB  - The typical assumption is that patients with CKD will have progressive
      nephropathy. Methodological issues, such as measurement error and regression to
      the mean, have made it difficult to document whether kidney function might
      improve in some patients. Here, we used data from 12 years of follow-up in the
      African American Study of Kidney Disease and Hypertension to determine whether
      some patients with CKD can experience a sustained improvement in GFR. We
      calculated estimated GFR (eGFR) based on serum creatinine measurements during
      both the trial and cohort phases. We defined clearly improved patients as those
      with positive eGFR slopes that we could not explain by random measurement
      variation under Bayesian mixed-effects models. Of 949 patients with at least
      three follow-up eGFR measurements, 31 (3.3%) demonstrated clearly positive eGFR
      slopes. The mean slope among these patients was +1.06 (0.12) ml/min per 1.73 m(2)
      per yr, compared with -2.45 (0.07) ml/min per 1.73 m(2) per yr among the
      remaining patients. During the trial phase, 24 (77%) of these 31 patients also
      had clearly positive slopes of (125)I-iothalamate-measured GFR during the trial
      phase. Low levels of proteinuria at baseline and randomization to the lower BP
      goal (mean arterial pressure <=92 mmHg) associated with improved eGFR. In
      conclusion, the extended follow-up from this study provides strong evidence that
      kidney function can improve in some patients with hypertensive CKD.

PMID- 22402804
TI  - Initial experience with tadalafil in pediatric pulmonary arterial hypertension.
AB  - This study aimed to investigate the safety, tolerability, and effects of
      tadalafil on children with pulmonary arterial hypertension (PAH) after transition
      from sildenafil or after tadalafil received as initial therapy. A total of 33
      pediatric patients with PAH were retrospectively evaluated. Of the 33 patients,
      29 were switched from sildenafil to tadalafil. The main reason for the change
      from sildenafil was once-daily dosing. The average dose of sildenafil was 3.4 +/-
      1.1 mg/kg/day, and that of tadalafil was 1.0 +/- 0.4 mg/kg/day. For 14 of the 29
      patients undergoing repeat catheterization, statistically significant
      improvements were observed after transition from sildenafil to tadalafil in terms
      of mean pulmonary arterial pressure (53.2 +/- 18.3 vs. 47.4 +/- 13.7 mmHg; p <
      0.05) and pulmonary vascular resistance index (12.2 +/- 7.0 vs 10.6 +/- 7.2
      Units/m(2); p < 0.05). Clinical improvement was noted for four patients treated
      with tadalafil as initial therapy. The side effect profiles were similar for the
      patients who had transitioned from sildenafil to tadalafil including headache,
      nausea, myalgia, nasal congestion, flushing, and allergic reaction. Two patients
      discontinued tadalafil due to migraine or allergic reaction. One patient
      receiving sildenafil had no breakthrough syncope after transition to tadalafil.
      Tadalafil can be safely used for pediatric patients with PAH and may prevent
      disease progression.

PMID- 22402805
TI  - Catheter interventional closure of a large right pulmonary artery-to-left atrial
      communication in a neonate.
AB  - Right pulmonary artery-to-left atrial communication is a rare congenital vascular
      malformation that results in a right-to-left shunting. This report describes the
      case history of a neonate with a large right pulmonary artery-to-left atrial
      connection resulting in cyanosis and severe heart failure who underwent
      successful early catheter interventional therapy. In the neonate, this lesion can
      be diagnosed accurately using transthoracic echocardiography. Closure of the
      communication can be achieved even in infants via percutaneous interventional
      catheterization with a low procedure-related risk and a good midterm follow-up
      result.

PMID- 22402806
TI  - Photoswitchable mixed valence.
AB  - For a molecular electronics technology to be fully serviceable, switching
      functions will be indispensable. Specifically, it will be desirable to control
      the conductivity of a given molecule using an external stimulus. This tutorial
      review discusses photoswitchable mixed valence systems that are comprised of a
      reversibly photoisomerizable bridging unit connecting two redox-active moieties,
      and as such represent some of the most simple chemical systems in which switching
      of charge delocalization can be explored. As photoisomerizable units,
      dithienylethenes have received much attention in the context of photoswitchable
      mixed valence, but there are also more exotic examples such as norbornadiene- and
      dimethyldihydropyrene-based switchable systems. As redox-active units responsible
      for the mixed valence phenomenon, both metal-containing as well as purely organic
      moieties have been employed. Typical investigations in this area involve the
      comparison of cyclic voltammograms and (near-infrared) optical absorption spectra
      of the two isomeric forms of a given system. The magnitude of the
      comproportionation constant and evaluation of intervalence absorption bands using
      appropriate theoretical models yield information regarding the extent of charge
      delocalization in the two isomeric forms. In several of the compounds
      investigated so far, the light stimulus induces a substantial increase of charge
      delocalization, or in the terminology commonly used in mixed valence chemistry, a
      changeover from class I to class II or even class III behavior.

PMID- 22402807
TI  - Bioactive component, cantharidin from Mylabris cichorii and its antitumor
      activity against Ehrlich ascites carcinoma.
AB  - The anticancer activity of the extract of blister beetle, Mylabris cichorii has
      been documented earlier by us. In the present study, the active principle of M.
      cichorii was isolated and its anticancer efficacy was evaluated against murine
      Ehrlich ascites carcinoma (EAC). The isolated bioactive compound was
      characterized to be cantharidin which showed potent antitumor activity and
      inhibited the proliferation of Ehrlich ascites carcinoma, both in vivo and in
      vitro. Cantharidin-treated EAC-bearing mice showed about 82% increase in lifespan
      at the dose of 0.5 mg/kg/day. In vitro cytotoxicity assay with the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test revealed about 50%
      cell death at the concentration of 25.8 MUg/ml. The fluorescence and transmission
      electron microscopy revealed that EAC cells treated with cantharidin depicted
      typical apoptotic morphology with chromatin condensation, nuclear fragmentation
      into discrete masses, and plasma membrane blebbing which deduce towards the death
      of these cells. Histological examination of the kidney of cantharidin-treated
      mice showed glomerular and tubular congestion with abnormal Bowman's capsule,
      thus, indicating a renal toxicity in the host. Cantharidin-induced renal damage
      in the host was also manifested by the decreased lactate dehydrogenase isozymes
      and its possible release from the cells.

PMID- 22402808
TI  - High 10-year survival rate with an anatomic cementless stem (SPS).
AB  - BACKGROUND: Proximal cementless fixation using anatomic stems reportedly
      increases femoral fit and avoids stress-shielding. However, thigh pain was
      reported with the early stem designs. Therefore, a new anatomic cementless stem
      design was based on an average three-dimensional metaphyseal femoral shape.
      However, it is unclear whether this stem reduces the incidence of thigh pain.
      QUESTIONS/PURPOSES: We asked whether this stem design was associated with a low
      incidence of thigh pain and provided durable fixation and high function. METHODS:
      One hundred seventy-one patients (176 THAs) who had the anatomic proximal
      hydroxyapatite-coated stem implanted were reviewed. Eleven (6%) patients were
      lost to followup and 34 (20%) died without revision surgery. We used the Harris
      hip score (HHS) to assess pain and function. We evaluated femoral stem fixation
      and stability with the score of Engh et al. and also calculated a 10-year
      survival analysis. We assessed 126 patients (131 hips) at a mean followup of 10
      years (range, 8-11 years) RESULTS: At last followup, two patients described
      slight thigh pain that did not limit their physical activities. All stems
      appeared radiographically stable and one stem was graded nonintegrated but
      stable. Five patients had revision surgery: one on the femoral side (for
      posttraumatic fracture) and four on the acetabular side. Considering stem
      revision for aseptic loosening as the end point, survivorship was 100% (range,
      95.4%-99.9%) at 10 years. CONCLUSION: This anatomic cementless design using only
      metaphyseal fixation with a wide mediolateral flare, a sagittal curvature, and
      torsion, allowed durable proximal stem stability and fixation.

PMID- 22402809
TI  - The classic: Hospital for the cure of deformities: course of lectures on the
      deformities of the human frame. 1843.
AB  - This Classic Article is a reprint of the original work by W.J. Little, Hospital
      for the Cure of Deformities: Course of Lectures on the Deformities of the Human
      Frame. An accompanying biographical sketch of W.J. Little is available at DOI
      10.1007/s11999-012-2301-z . The Classic Article is (c)1843 and is reprinted
      courtesy of Elsevier from Little WJ. Hospital for the Cure of Deformities: course
      of lectures on the deformities of the human frame. Lancet. 1843;41:350-354.

PMID- 22402810
TI  - Perioperative clopidogrel and postoperative events after hip and knee
      arthroplasties.
AB  - BACKGROUND: Hip and knee arthroplasties are widely performed and vascular disease
      among patients having these procedures is common. Clopidogrel is a platelet
      inhibitor that decreases the likelihood of thrombosis. It may cause
      intraoperative and postoperative bleeding, but its discontinuation increases the
      risk of vascular events. There is currently no consensus regarding the best
      perioperative clopidogrel regimen that balances these concerns.
      QUESTIONS/PURPOSES: We determined (1) the relationship between time of
      perioperative clopidogrel administration and postoperative bleeding-related
      events after hip and knee arthroplasties and (2) patient characteristics or
      surgical factors that may predict these events. METHODS: We retrospectively
      queried our inpatient pharmacy database for patients who received clopidogrel
      from 2007 to 2009 and identified 116 patients who underwent hip or knee
      arthroplasty. We recorded the time of perioperative clopidogrel administration,
      bleeding-related postoperative events, patient characteristics, and surgical
      factors. RESULTS: Patients who withheld clopidogrel 5 or more days before hip or
      knee arthroplasty had lower rates of reoperation for infection and antibiotics
      prescribed for the surgical wound. Postoperative events did not vary with timing
      of clopidogrel resumption after surgery. Advanced age, an American Society of
      Anesthesiologists (ASA) score of 4, and revision surgery predicted increased
      readmission, reoperation for hematoma or infection, antibiotic use, and death.
      CONCLUSIONS: Holding clopidogrel for at least 5 days before hip or knee
      arthroplasty may lower the rate of bleeding-related events. We found no increase
      in events when patients resumed clopidogrel immediately after surgery. Advanced
      age, ASA score of 4, and revision surgery may be risk factors for bleeding
      related events. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 22402811
TI  - Liver injury due to chemotherapy-induced sinusoidal obstruction syndrome is
      associated with sinusoidal capillarization.
AB  - BACKGROUND: Indocyanine green (ICG) retention is a validated test of hepatic
      function in patients with chronic liver disease. The underlying mechanism for the
      impairment of ICG retention in patients undergoing chemotherapy for colorectal
      liver metastases (CLM) remains unclear. We sought to elucidate the mechanism for
      impairment of ICG retention in patients with CLM. METHODS: Clinicopathologic data
      of 98 patients with CLM undergoing hepatectomy were analyzed. The archived
      nontumoral liver parenchyma bearing no CLM were immunostained with CD34 antibody
      to determine the sinusoidal capillarization. RESULTS: Of 98 patients, 80 received
      preoperative chemotherapy. Sinusoidal obstruction syndrome (SOS) occurred in 39
      patients (39.8%). The development of SOS in patients receiving oxaliplatin-based
      chemotherapy was significantly higher compared to those receiving non-oxaliplatin
      based chemotherapy (P=0.003). SOS was independently associated with abnormal ICG
      retention rate at 15 minutes (ICG-R15) (odds ratio 3.45, 95% confidence interval
      1.31-9.04, P=0.012) and CD 34 overexpression (odds ratio 18.76, 95% confidence
      interval 4.58-76.81, P<0.001). ICG-R15 correlated with CD34 expression within the
      nontumoral liver parenchyma (r=0.707, P<0.001) and severity of SOS (r=0.423,
      P<0.001). CD34 positive areas were likely situated at the peripheral area of SOS,
      and both SOS score and number of cycles of oxaliplatin-based chemotherapy
      significantly correlated with CD34 expression (r=0.629, P<0.001 and r=0.522,
      P<0.001, respectively). CONCLUSIONS: These results suggest that the deterioration
      of hepatic functional reserve due to SOS is associated with sinusoidal
      capillarization, indicated by CD34 overexpression within nontumoral liver
      parenchyma adjacent to SOS.

PMID- 22402812
TI  - Risk factors of peritoneal recurrence and outcome of resected peritoneal
      recurrence after liver resection in hepatocellular carcinoma: review of 1222
      cases of hepatectomy in a tertiary institution.
AB  - BACKGROUND: Reports on the risk factors of peritoneal recurrence (PR) after liver
      resection for hepatocellular carcinoma are lacking. We examined the risk factors
      of PR after hepatectomy and the outcome of resected PR at our institution.
      METHODS: We retrospectively reviewed the data from 1,222 patients who underwent
      hepatectomies for hepatocellular carcinoma in Samsung Medical Center from January
      2006 to August 2010. We identified patients with PR and studied the risk factors
      and outcomes of resected PR. RESULTS: The rate of PR was 3.0% (n=36). The mean+/
      SD age of patients was 54.0+/-10.2 years. Among those with PR, 23 patients
      (63.9%) had unresectable disease and 13 patients (36.1%) had resectable disease.
      Multivariate analysis found that tumor size>50 mm, presence of microvascular
      invasion, bile duct invasion, and positive margins were significant risk factors
      of PR after liver resection. The median overall survival (OS) for resectable PR
      was 33.0 (28.0-61.6) months compared to 14.0 (6.8-21.2) months for unresectable
      PR (P=0.009). Cox regression analysis demonstrated that resected PR [hazard ratio
      (HR) 0.042, P = 0.001] and interval between hepatectomy and PR (>6 months) (HR
      0.195, P=0.016) were positive prognostic factors for OS, while alfa
      fetoprotein>200 ng/dl at detection of PR (HR 11.321, P=0.015) and serosal
      involvement of primary hepatocellular carcinoma (HR 25.616, P=0.007) were
      negative prognostic factors for OS. CONCLUSIONS: We found that tumor size>50 mm,
      presence of microvascular invasion, bile duct invasion, and positive resection
      margins were significant risk factors of PR after liver resection. Selected
      patients with resected PR had significantly better OS.

PMID- 22402813
TI  - Management of the neck in the setting of definitive chemoradiation: is there a
      consensus? A GETTEC study.
AB  - BACKGROUND: The management of the neck remains controversial in the definitive
      chemoradiation setting of advanced N2-3 head and neck squamous cell carcinoma.
      Most published data favor omission of neck dissection (ND) after complete
      response for N2-3 or selective ND for residual disease METHODS: We studied the
      patterns of care in the French-Belgian Groupe d'Etude des Tumeurs de la Tete Et
      du Cou (GETTEC) through a questionnaire-based survey. RESULTS: Eighteen percent
      of institutions never performed up-front ND, 20% rarely, 40% sometimes, 14%
      often, and 8% systematically. Induction chemotherapy was indicated in 30% of the
      cases, and most ND were performed either between induction and radiation or after
      chemoradiation for residual disease. Response to chemoradiation was assessed by
      computed tomographic scan and positron emission tomography in 72% of cases.
      Selective ND was more common than radical ND. CONCLUSIONS: Omission of ND based
      on computed tomographic scan and positron emission tomography-based complete
      response to chemoradiation is the most common strategy for advanced nodal disease
      among centers. However, neck management strategies vary among institutions, and
      some institutions continue advocating systematic ND before irradiation. The new
      treatment options and the changing epidemiology, namely docetaxel-based induction
      chemotherapy and human papilloma virus-related head and neck squamous cell
      carcinoma having better response profiles and prognosis, are adding to the
      nonconsensual approach. The best therapeutic index in terms of neck management
      remains to be defined in this evolving context.

PMID- 22402814
TI  - Outcomes after tumescence technique versus electrocautery mastectomy.
AB  - BACKGROUND: Tumescence is the injection of local anesthetic and crystalloid into
      the subcutaneous tissue to establish a bloodless plane for surgical dissection.
      The aim of our study was to evaluate outcomes after mastectomy with tumescent
      technique compared to electrocautery dissection. METHODS: We conducted a single
      institution retrospective evaluation of patients who underwent mastectomy between
      2007 and 2011. The tumescent technique was performed by injecting 1% lidocaine
      with epinephrine mixed in a 10% ratio with lactated Ringer solution into the
      mastectomy flaps followed by sharp dissection. Significance testing was done to
      evaluate for outcome differences between the two surgical groups. RESULTS: Among
      the 134 patients, 64 underwent electrocautery and 70 underwent tumescent-assisted
      dissection. The overall complication rate was 21.6% (tumescent, 20.0%;
      electrocautery, 23.4%, P = 0.63). Flap necrosis requiring operative debridement
      was the most common complication in the tumescent group (n = 6). On multivariate
      analysis, tumescent technique was not associated with an increased complication
      rate. Immediate reconstruction was the only factor that increased the risk of
      complication (odds ratio 12.95, P < 0.001). CONCLUSIONS: The tumescence surgery
      technique should be utilized with caution in patients undergoing immediate
      reconstruction, as a trend for higher complication rates was observed in these
      cases, and flap viability is particularly important in this setting. Future
      prospective studies are needed to further evaluate blood loss, operative time,
      postoperative pain, and duration of drainage catheters after tumescent mastectomy
      technique.

PMID- 22402815
TI  - Viral and bacterial aetiologies of epithelial ovarian cancer.
AB  - We sought to analyse the presence of human papillomavirus (HPV), Chlamydia
      trachomatis and cytomegalovirus (CMV) infection in women with epithelial ovarian
      carcinomas. Polymerase chain reaction (PCR)-based detection of microbial
      infections was carried out. A total of 39 tissue samples were analysed with
      consensus and type-specific primers for HPV, primers specific for the cryptic
      plasmid of Chlamydia and primers for glycoprotein B of CMV. The samples analysed
      showed 40%, 80% and 50% positivity for HPV, Chlamydia and CMV infection,
      respectively, in cancerous ovarian tissues. The HPV type detected was HPV 6, with
      its genome integrated to the host genome in case of both invasive and borderline
      tumours and existed episomally in healthy controls. The patients with Chlamydia
      (odds ratio [OR] 32; 95% confidence interval [CI] 3.33, 307.65) and CMV infection
      (OR 8; 95% CI 0.888, 72.10) are at significantly higher risk of development of
      ovarian tumours. The present study validates the theory of chronic infections and
      inflammation in the pathogenesis of epithelial ovarian cancer. Further
      seroepidemiological studies and large fresh tissue sampling may represent the
      real prevalence of infections among ovarian carcinoma patients. This study is the
      first of its kind in detecting the bacterial and viral aetiologies in the
      development of ovarian carcinoma among Indian women.

PMID- 22402816
TI  - A Pneumocystis jirovecii pneumonia outbreak in a single kidney-transplant center:
      role of cytomegalovirus co-infection.
AB  - Pneumocystis jirovecii pneumonia (PCP) and cytomegalovirus (CMV) infection
      represent possible complications of medical immunosuppression. Between 2005 and
      2010, non-human immunodeficiency virus (HIV) PCP patients admitted to a
      nephrology unit were analyzed for outcome, CMV comorbidity, and patient-to
      patient contacts prior to PCP. In contrast to 2002-2004 (no cases) and 2008-2010
      (10 cases), a PCP outbreak of 29 kidney-transplant recipients and one patient
      with anti-glomerular basement membrane disease occurred between 2005 and 2007.
      None of the patients were on PCP chemoprophylaxis. In four PCP patients, the
      genotyping data of bronchoalveolar lavage specimen showed an identical
      Pneumocystis strain. PCP cases had a higher incidence of CMV infection (12 of 30
      PCP patients) and CMV disease (four patients) when compared to matched PCP-free
      controls (p < 0.05). Cotrimoxazole and, if applicable, ganciclovir were started
      2.0 +/- 4.0 days following admission, and immunosuppressive medication was
      reduced. In-hospital mortality was 10% and the three-year mortality was 20%. CMV
      co-infection did not affect mortality. CMV co-infection more frequently occurred
      during a cluster outbreak of non-HIV PCP in comparison to PCP-free controls.
      Here, CMV awareness and specific therapy of both CMV infection and PCP led to a
      comparatively favorable patient outcome. The role of patient isolation should be
      further investigated in incident non-HIV PCP.

PMID- 22402817
TI  - Microscopic and UPLC-UV-MS analyses of authentic and commercial yohimbe
      (Pausinystalia johimbe) bark samples.
AB  - Yohimbine is the major alkaloid found in the stem bark of yohimbe, Pausinystalia
      johimbe (Rubiaceae), an evergreen tree native to Africa. The objectives of the
      current study were to provide a detailed anatomy of yohimbe bark, as well as to
      determine the quantity of yohimbine in the raw yohimbe products sold online.
      Twelve commercial raw materials of yohimbe were analyzed by microscopic and ultra
      performance liquid chromatography-UV-MS methods. The study revealed that three
      samples were probably adulterated and four other samples contained various levels
      of impurities. Yohimbine was not detected in one sample, whereas its presence in
      other samples was found to be in the range 0.1-0.91%. The present work also
      provides a detailed anatomy of the stem bark of yohimbe, with light and scanning
      electron microscopy images, for proper identification and authentication.

PMID- 22402818
TI  - Morphological and molecular identification of the ectomycorrhizal association of
      Lactarius fumosibrunneus and Fagus grandifolia var. mexicana trees in eastern
      Mexico.
AB  - A population of Fagus grandifolia var. mexicana (covering ca. 4.7 ha) is
      established in a montane cloud forest refuge at Acatlan Volcano in eastern Mexico
      (Veracruz State), and it represents one of only ten populations of this species
      known to occur in the country (each stand covers ca. 2-35 ha in extension) and
      one of the southernmost in the continent. Sporocarps of several ectomycorrhizal
      macrofungi have been observed in the area, and among them, individuals of the
      genus Lactarius are common in the forest. However, the morphological and
      molecular characterization of ectomycorrhizae is still in development. Currently,
      two species of Lactarius have been previously documented in the area. Through the
      phylogenetic analysis of the internal transcribed spacer (ITS) region from
      basidiomes and ectomycorrhizae, we identified the Lactarius fumosibrunneus
      ectomycorrhiza. The host, F. grandifolia var. mexicana, was determined comparing
      the amplified ITS sequence from ectomycorrhizal root tips in the GenBank database
      with Basic Local Alignment Search Tool. The mycorrhizal system of L.
      fumosibrunneus is monopodial-pyramidal, characterized by its shiny, white to
      silver and pruinose surface, secreting a white latex when damaged, composed of
      three plectenchymatous mantle layers, with diverticulated terminal elements at
      the outer mantle. It lacks emanating hyphae, rhizomorphs, and sclerotia. A
      detailed morphological and anatomical description, illustrations, and photographs
      of the ectomycorrhiza are presented. The comparison of L. fumosibrunneus and
      other Lactarius belonging to subgenus Plinthogalus is presented.

PMID- 22402820
TI  - New developments of dopaminergic imaging in Parkinson's disease.
AB  - The development of radioligands for the dopaminergic system has provided suitable
      imaging biomarkers for clinical research in Parkinson's disease (PD) and related
      movement disorders. Single photon emission tomography (SPECT) has played an
      important role as main molecular imaging modality because of the availability of
      imaging tools such as dopamine transporter (DAT) radioligands for wide clinical
      use. At present, SPECT imaging of the DAT is the main diagnostic imaging
      procedure for the assessment of patients with parkinsonism. However, in the
      recent years positron emission tomography (PET) has become an important clinical
      diagnostic modality, mainly in oncology, due to the wide availability of PET/CT
      systems with improved imaging performance and to the use of 2-deoxy-2-[18F]fluoro
      D-glucose ([18F]FDG) as main diagnostic agent. In this context, further
      development of 18F-radioligands is of high interest for their potential utility
      in the clinical setting. This review will give a general overview on the
      development of SPECT and PET radioligands for the dopaminergic system and
      describe the potential advantages of developing 18F-labelled radioligands for
      imaging of the dopaminergic system in PD and related movement disorders.

PMID- 22402819
TI  - Controlled generation of submicron emulsion droplets via highly stable tip
      streaming mode in microfluidic devices.
AB  - Submicron emulsions could be produced via the tip-streaming process in a flow
      focusing microfluidic device. In this article, the stability of the liquid cone
      and thread for tip-streaming mode could be significantly improved by employing a
      three-dimensional flow-focusing device, in which the hydraulic resistance was
      adjusted by modulating the channel heights in the flow focusing area, orifice,
      downstream and dispersed phase inlet channel. The pressure range for tip
      streaming mode was enlarged significantly compared with two-dimensional flow
      focusing devices. Therefore, monodisperse emulsions were produced under this tip
      streaming mode for as long as 48 hours. Furthermore, we could control the size of
      emulsion drops by changing the pressure ratio in three-dimensional flow-focusing
      devices while the liquid cone was easily retracted during the adjustment of
      pressure ratio in two-dimensional flow-focusing devices. Furthermore, using the
      uniform submicron emulsion droplets as confining templates, polyethylene glycol
      (PEG) particles were produced with a narrow size distribution at the sub
      micrometre scale. In addition, magnetic nanoparticles were added to the emulsion
      for magnetic PEG particles, which can respond to magnetic field and would be
      biocompatible.

PMID- 22402821
TI  - [11C]choline PET for the intraprostatic tumor characterization and localization
      in recurrent prostate cancer after EBRT.
AB  - AIM: This study focuses on the potential role of [11C]choline positron emission
      tomography (PET) for the intraprostatic tumor characterization and localization
      in recurrent prostate cancer after EBRT. METHODS: This retrospective study was
      conducted in patients who were being followed up after EBRT for histological
      proven prostate cancer. We selected the patients with a local recurrence by
      [11C]choline PET/CT fusion. The results of PET were compared with the results of
      histology and with clinical follow-up. RESULTS: Forty-two patients with a local
      recurrence suggested by PET were included in this study. According to PET
      results: of the 42 patients, 15 (36%) had a focal recurrence, 27 (64%) showed a
      diffuse recurrence. The overall concordance of PET with histology concerning
      detection of recurrence was 76% (32 patients had positive PET results and
      positive biopsies). We confirmed the local recurrence as visualized by PET in
      37/42 (88%) patients using a composite reference with histology and clinical
      follow up after local salvage treatment. The concordance of the intraprostatic
      distribution of the tumor with PET with histology from transrectal prostate
      biopsies (median biopsies 7, range 4-12) was 47% (7/15) in unilateral cases and
      41% (11/27) in bilateral cases. No significant differences were seen between the
      2 groups in serum PSA at time of PET (P=0.509) and SUV (P=0.739) using Student's
      t-test. CONCLUSION: Intraprostatic characterization of recurrent prostate cancer
      after EBRT with 11C-choline PET is feasible at present but shows a moderate
      concordance with routine transrectal prostate biopsies. The accuracy is too low
      for the routine use of this modality in the present scenario.

PMID- 22402822
TI  - The impact of PET and PET/CT on treatment planning and prognosis of patients with
      NSCLC treated with radiation therapy.
AB  - AIM: 18F fluoro-deoxy-glucose (FDG) positron emission tomography (PET)-imaging
      improves the diagnostic accuracy in staging non small cell lung cancer (NSCLC)
      with possible impact on survival. This prospective study aimed to investigate the
      impact of PET and PET/CT on treatment planning and prognosis in patients with
      NSCLC treated with radiation therapy. METHODS: From October 2003 to January 2008,
      91 consecutive patients with proven NSCLC stage T1-4N0-3M0 (clinical stages: I
      IIIb) underwent accelerated, twice daily radiation therapy in target splitting
      technique. 70 patients received chemotherapy before radiation therapy (76%). All
      patients underwent PET or PET/CT-imaging and were followed up for a median time
      of 30 months. Imaging findings were interpreted visually and a SUV cut-off of 2.5
      was applied for delineation of tumor borders. Changes in staging and planning
      treatment volumes (PTV) due to PET or PET/CT-imaging and survival were defined as
      primary study endpoints. The impact of tumor-type, stage, age, gender, weight
      loss and FDG-uptake in PET imaging as measured by the standardized uptake value
      (SUV) on survival were analysed as secondary endpoints. RESULTS: PET imaging
      provided additional diagnostic information over CT alone in 20% (N.=18) of our
      study population, leading to upstaging in 17% of them, respectively. In 5
      patients (5.5% of 91) atelectasis could be separated from tumor tissue, PTV was
      altered in 9% (N.=8). 39 patients (43%) died during the observation period, mean
      overall survival was 32.3 months (95% Confidence intervalI 27.6-37.1) and tumor
      specific survival was 36.9 months (95 % CI 32.0-42.0), respectively. One- and two
      year survival rates reached 90.1% and 67.7%, respectively. Multivariate analysis
      did not reveal any significant prognostic impact of tumor-type, stage, age,
      gender or FDG-uptake as given by SUVmax (mean 13.6+/-6.8) or SUVmean (mean 5.5+/
      1.6). CONCLUSION: The use of FDG-PET- and PET/CT-imaging provided incremental
      information relevant for treatment-planning in about 10 % of patients with NSCLC
      undergoing accelerated radiation therapy with curative intent. This prospective
      trial did not provide evidence for the assumption that the SUV might be an
      independent predictor of outcome.

PMID- 22402824
TI  - Cascade synthesis of bis-N-sulfonylcyclobutenes via Cu(I)/Lewis acid-catalyzed (3
      + 2)/(2 + 2) cycloadditions: observation of aggregation-induced emission
      enhancement from restricted C=N photoisomerization.
AB  - A remarkable role of Lewis acid additives in syntheses of bis-N
      sulfonylcyclobutenes via copper(I) catalyzed (3 + 2)/(2 + 2) cycloaddition
      cascade of sulfonyl azides and terminal alkynes is described. In addition, these
      cyclobutenes display a unique aggregation-induced emission enhancement (AIEE),
      reported for the first time, arising predominantly from restricted rotation in
      C=N photoisomerization in the solid state.

PMID- 22402823
TI  - Randomized controlled trial on the long-term efficacy of a multifaceted,
      interdisciplinary lifestyle intervention in reducing cardiovascular risk and
      improving lifestyle in patients at risk of cardiovascular disease.
AB  - The objective of the study was to evaluate the efficacy of an interdisciplinary
      intervention known as Educoeur in reducing cardiovascular risk and improving
      health behaviors in people without evidence of cardiovascular disease and to
      compare the Educoeur program to interventions in a specialized clinic and in
      usual care family practice. In a parallel, randomized, controlled trial of 185
      adults with at least two modifiable cardiovascular risk factors, patients were
      randomly assigned to either Educoeur, specialized clinic or usual care.
      Cardiovascular risk, biological and lifestyle measures were assessed at baseline
      and at 2 years. In Educoeur, measurements were also taken before and after the
      lifestyle group treatment program. In 12 weeks, patients in Educoeur
      significantly lowered their cardiovascular risk, weight, body mass index, waist
      circumference, systolic blood pressure, kilocalories intake and improved their
      VO2 Max and mental health. Changes remained significant at 2 years. Between group
      comparisons at 2 years demonstrated that Educoeur was significantly better in
      reducing cardiovascular risk than interventions in usual care. Together, these
      results highlight the importance of providing interdisciplinary programs that
      optimize cardiovascular risk reduction and promote active lifestyles in patients
      at risk of cardiovascular disease.

PMID- 22402829
TI  - Claudin-17 forms tight junction channels with distinct anion selectivity.
AB  - Barrier properties of tight junctions are determined by the claudin protein
      family. Many claudins seal this barrier, but others form paracellular channels.
      Among these, no claudins with general and clear-cut anion selectivity have yet
      been described, while for claudin-10a and claudin-4, only circumstantial or small
      anion selectivities have been shown. A claudin with unknown function and tissue
      distribution is claudin-17. We characterized claudin-17 by overexpression and
      knock-down in two renal cell lines. Overexpression in MDCK C7 cell layers caused
      a threefold increase in paracellular anion permeability and switched these cells
      from cation- to anion-selective. Knockdown in LLC-PK(1) cells indorsed the
      finding of claudin-17-based anion channels. Mutagenesis revealed that claudin-17
      anion selectivity critically depends on a positive charge at position 65. Claudin
      17 expression was found in two organs: marginal in brain but abundant in kidney,
      where expression was intense in proximal tubules and gradually decreased towards
      distal segments. As claudin-17 is predominantly expressed in proximal nephrons,
      which exhibit substantial, though molecularly not defined, paracellular chloride
      reabsorption, we suggest that claudin-17 has a unique physiological function in
      this process. In conclusion, claudin-17 forms channels within tight junctions
      with distinct anion preference.

PMID- 22402831
TI  - Developmental venous anomaly of the internal auditory canal in a child with
      unilateral sensorineural hearing loss--a rare association.
AB  - Developmental venous anomalies (DVAs) are extremely unusual in the
      cerebellopontine angle region and internal auditory canal, and constitute a rare
      etiology of unilateral sensorineural hearing loss (SNHL) in children. We report,
      to the best of our knowledge, one of the first documented cases of DVA as a
      probable cause of unilateral SNHL in a child. Our emphasis is on the radiological
      features.

PMID- 22402830
TI  - US in the diagnosis of gastroesophageal reflux in children.
AB  - Several techniques have been used to diagnose gastroesophageal reflux (GER) in
      children, but no single test is sufficiently accurate to completely investigate
      the problem. Gastroesophageal US has been described as a widely available,
      noninvasive and sensitive method. It provides morphological and functional
      information, but its role in the diagnosis of GER in children is still debated.
      In this paper we review diagnostic approaches to GER in children. We focus on
      current use of US in the management of children with suspected GER. Reports
      suggest that US allows exclusion of several non-GER causes of symptoms and that
      it provides morphological and functional data with high sensitivity and positive
      predictive value for the diagnosis of GER. Sonographic assessment of findings
      such as abdominal esophageal length, esophageal diameter, esophageal wall
      thickness and gastroesophageal angle provide important diagnostic indicators of
      reflux and related to the degree of GER. There is a need for standardization of
      the procedure and for defining diagnostic criteria.

PMID- 22402832
TI  - Multidetector CT-guided endovascular treatment of a splenic artery aneurysm in a
      child with split-liver transplant and surgically ligated splenic artery origin.
AB  - We report the case of a child who underwent left lateral split-liver
      transplantation for biliary atresia and surgical ligation of the origin of the
      splenic artery at the time of the transplantation. Post-transplant portal vein
      thrombosis was initially treated with a meso-rex shunt. This shunt subsequently
      thrombosed and was replaced by a splenorenal shunt. Three months after
      splenorenal shunt placement, US showed a 3.7-cm pseudoaneurysm at the hilum of
      the spleen. Multidetector CT with 3-D reconstruction allowed precise
      identification of the pseudoaneurysm feeding artery and therefore helped in
      planning the interventional radiology procedure, avoiding explorative selective
      catheterisation. The pseudoaneurysm was successfully treated with endovascular
      coil embolisation.

PMID- 22402833
TI  - A critical evaluation of US for the diagnosis of pediatric acute appendicitis in
      a real-life setting: how can we improve the diagnostic value of sonography?
AB  - BACKGROUND: We have observed that day-to-day use of US for acute appendicitis
      does not perform as well as described in the literature. OBJECTIVE: Review the
      diagnostic performance of US in acute appendicitis with attention to factors that
      influence performance. MATERIALS AND METHODS: Retrospective review of all
      sonograms for acute appendicitis in children from May 2005 to May 2010 with
      attention to the rate of identification of the appendix, training of personnel
      involved and diagnostic accuracy. RESULTS: The appendix was identified in
      246/1,009 cases (24.4%), with identification increasing over time. The accuracy
      of US was 85-91% with 35 false-positives and 54 false-negatives. Pediatric
      sonographers were significantly better at identifying the appendix than non
      pediatric sonographers (P < 0.0001). Increased weight was the only patient factor
      that influenced identification of the appendix (P = 0.006). CT use was stable
      over the 5 years but declined in cases where the appendix was identified by US.
      CONCLUSION: In day-to-day use, US does not perform as purported in the
      literature. We do not visualize the appendix as often as we should and false
      negative and false-positive exams are too common. To improve the diagnostic
      performance of this modality, involvement by experienced personnel and/or
      additional training is needed.

PMID- 22402834
TI  - Stress stimulates production of catecholamines in rat adipocytes.
AB  - The sympathoadrenal system is the main source of catecholamines (CAs) in adipose
      tissues and therefore plays the key role in the regulation of adipose tissue
      metabolism. We recently reported existence of an alternative CA-producing system
      directly in adipose tissue cells, and here we investigated effect of various
      stressors-physical (cold) and emotional stress (immobilization) on dynamics of
      this system. Acute or chronic cold exposure increased intracellular
      norepinephrine (NE) and epinephrine (EPI) concentration in isolated rat
      mesenteric adipocytes. Gene expression of CA biosynthetic enzymes did not change
      in adipocytes but was increased in stromal vascular fraction (SVF) after 28 day
      cold. Exposure of rats to a single IMO stress caused increases in NE and EPI
      levels, and also gene expression of CA biosynthetic enzymes in adipocytes. In SVF
      changes were similar but more pronounced. Animals adapted to a long-term cold
      exposure (28 days, 4 degrees C) did not show those responses found after a single
      IMO stress either in adipocytes or SVF. Our data indicate that gene machinery
      accommodated in adipocytes, which is able to synthesize NE and EPI de novo, is
      significantly activated by stress. Cold-adapted animals keep their adaptation
      even after an exposure to a novel stressor. These findings suggest the
      functionality of CAs produced endogenously in adipocytes. Taken together, the
      newly discovered CA synthesizing system in adipocytes is activated in stress
      situations and might significantly contribute to regulation of lipolysis and
      other metabolic or thermogenetic processes.

PMID- 22402835
TI  - Dual effect of methylglyoxal on the intracellular Ca2+ signaling and neurite
      outgrowth in mouse sensory neurons.
AB  - The formation of advanced glycation end products is one of the major factors
      involved in diabetic neuropathy, aging, and neurodegenerative diseases. Reactive
      carbonyl compounds, such as methylglyoxal (MG), play a key role in cross-linking
      to various proteins in the extracellular matrix, especially in neurons, which
      have a high rate of oxidative metabolism. The MG effect was tested on dorsal root
      ganglia primary neurons in cultures from adult male Balb/c mice. Lower MG doses
      contribute to an increased adherence of neurons on their support and an increased
      glia proliferation, as proved by MTS assay and bright-field microscopy. Time
      lapse fluorescence microscopy by Fura-2 was performed for monitoring the relative
      fluorescence ratio changes (DeltaR/R(0)) upon depolarization and
      immunofluorescence staining for quantifying the degree of neurites extension. The
      relative change in fluorescence ratio modifies the amplitude and dispersion
      depending on the subtype of sensory neurons, the medium-sized neurons are more
      sensitive to MG treatment when compared to small ones. Low MG concentrations (0
      150 MUM) increase neuronal viability, excitability, and the capacity of neurite
      extension, while higher concentrations (250-750 MUM) are cytotoxic in a dose
      dependent manner. In our opinion, MG could be metabolized by the glyoxalase
      system inside sensory neurons up to a threshold concentration, afterwards
      disturbing the cell equilibrium. Our study points out that MG has a dual effect
      concentration dependent on the neuronal viability, excitability, and neurite
      outgrowth, but only the excitability changes are soma-sized dependent. In
      conclusion, our data may partially explain the distinct neuronal modifications in
      various neurodegenerative pathologies.

PMID- 22402836
TI  - Antioxidant activities of polyphenols extracted from olive (Olea europaea) of
      chamlal variety.
AB  - The antioxidant properties of phenolic compounds from olive pulp (PCO) of chamlal
      variety and those of individual phenolic compounds were evaluated and compared
      with that of vitamin C (Vit C). The antioxidant activity was measured by the
      tests of iron reduction and scavenging hydrogen peroxide (H(2)O(2)). Results
      showed that all the substances tested exhibit a reducing power. The PCO present
      activities of iron reduction and H(2)O(2) scavenging higher than those of Vit C.
      The protective effect of PCO against oxidation of lipids and proteins from
      erythrocyte membranes was studied. The measurement of malondialdehyde generated
      under oxidative stress conditions induced by hydroxyl radicals generating system
      revealed that PCO have the most significant protective activity against lipid
      peroxidation (IC(50) = 49.27 +/- 1.91 MUg mL(-1)). Paradoxically, Vit C revealed
      a pro-oxidant effect. Proteins oxidation was evaluated using the H(2)O(2)/FeSO(4)
      system and electrophoresis. In the presence of PCO at 1 mg mL(-1), proteins of
      erythrocyte membranes were protected contrary to those treated with Vit C at the
      same concentration.

PMID- 22402837
TI  - Fluorimetric detection of Mg2+ and DNA with 9-(alkoxyphenyl)benzo[b]quinolizinium
      derivatives.
AB  - A benzo[b]quinolizinium-benzo-15-crown-5 ether conjugate 2a is presented that
      enables the fluorimetric detection of Mg(2+) and DNA by a significant light-up
      effect, along with a change of the emission wavelength with different analytes
      (Mg(2+): 495 nm; DNA: 550 nm). The mechanism of the excited-state deactivation of
      2a was investigated by steady-state fluorescence spectroscopy in media of varied
      viscosity and compared with the photophysical properties of methoxyphenyl
      substituted benzo[b]quinolizinium 2b (m,p-diOMe), 2c (m-OMe), and 2d (p-OMe) as
      reference compounds. Compounds 2a-c, which share the m-alkoxyphenyl substituent
      as the common feature, have low emission quantum yields (Phi(F) < 10(-2) in
      water) but exhibit a significant increase of their fluorescence intensity in
      viscous glycerol solutions. In contrast, the viscosity of the medium does not
      influence the emission properties of the parent phenyl-substituted
      benzo[b]quinolizinium 2e and of the p-methoxyphenyl-substituted derivative 2d.
      Based on these observations it is concluded that the excited-state deactivation
      in 2a-c is mainly due to the rotation of the m-alkoxy group about the C(ar)-O
      bond. The interaction of 2a-c with DNA or Mg(2+) ions was studied by
      spectrophotometric titrations and CD spectroscopy. Notably, the association of 2a
      or 2b with DNA or 2a with Mg(2+) ions induces a strong fluorescence enhancement
      (15- and 40-fold for DNA, 450-fold for Mg(2+)), which is rationalized by the
      suppression of the torsional-relaxation of the alkoxy-substituent in the excited
      state. Additionally, the cation-induced light-up effect of 2a is selective
      towards Mg(2+) ions as compared with other cations such as NH(4)(+), Li(+),
      Na(+), K(+) and Ba(2+).

PMID- 22402839
TI  - Comparison of aprotinin and tranexamic acid in adult scoliosis correction
      surgery.
AB  - PURPOSE: A retrospective review of consecutive adult patients undergoing
      scoliosis correction surgery was performed to compare the effects of aprotinin
      and tranexamic acid in blood conservation and to define a comprehensive blood
      conservation strategy for such surgery. METHODS: Medical records of all patients
      who underwent scoliosis correction surgery in this unit between January 2003 and
      December 2008 were reviewed. The patients were divided into three cohorts: group
      1 receiving no antifibrinolytics, group 2 aprotinin and group 3 tranexamic acid.
      Information was collected regarding number of vertebral levels fused, pre- and
      post-operative haemoglobin, intra-operative blood loss and peri-operative
      autologous and allogenic blood transfusion performed. RESULTS: Aprotinin was used
      in 28 patients (38%), tranexamic acid in 26 (36%), while 19 (26%) received no
      antifibrinolytics. 21 patients had anterior surgery, 34 patients had posterior
      surgery and 18 had combined anterior and posterior procedures. Mean blood loss in
      the patients who received aprotinin and tranexamic acid was 710 and 738 ml,
      respectively. This was significantly less than the patients receiving no
      antifibrinolytics (972 ml, p = 0.037). Blood transfusion was required in only two
      patients undergoing anterior correction surgery. CONCLUSION: Aprotinin and
      tranexamic acid reduce blood loss in adult spinal deformity correction surgery.
      With aprotinin being unavailable for clinical use, we recommend the use of
      tranexamic acid along with other blood conservation measures for adult spinal
      deformity correction surgery.

PMID- 22402840
TI  - Direct lateral access lumbar and thoracolumbar fusion: preliminary results.
AB  - PURPOSE: To describe the clinical outcomes and complications in a consecutive
      series of extreme lateral interbody fusion cases. METHODS: Retrospective cohort
      review of 97 consecutive patients from three centers with minimum 6-month follow
      up (mean 12 months). Functional status was evaluated by preoperative and last
      follow-up Oswestry Disability Index score. Leg and back pain were evaluated by
      visual analog scales. Complications were recorded and permanent complications and
      neurological impairment was actively investigated at last follow-up. RESULTS: No
      permanent neurological impairment, vascular or visceral injuries were observed.
      Transient neurological symptoms presented in 7% of cases, all resolved within 1
      month from surgery. Transient thigh discomfort was observed in 9%. Clinical
      success was recorded in 92% of cases. CONCLUSIONS: Extreme lateral interbody
      fusion is a safe and effective technique for anterior interbody fusion.

PMID- 22402841
TI  - Posterior lumbar fusion by peek rods in degenerative spine: preliminary report on
      30 cases.
AB  - PURPOSE: Pre-curved peek rods to support posterior lumbar fusion have been
      available in the market since 4 years. Potential advantages using this new
      technology are increased load sharing on the anterior column promoting interbody
      fusion, reduced stress on bone-screw interface decreasing the rate of screw
      mobilization and, in the long term, reduced incidence of adjacent level disc
      degeneration. METHODS: The authors retrospectively reviewed 30 cases in which
      posterior fusion was supported by peek rods, analyzing early complications, rate
      of fusion and clinical outcome. RESULTS: At an average follow-up of 18 months,
      both clinical and radiographic results were satisfactory with only one case
      requiring surgical revision for a mechanical complication. CONCLUSIONS: The semi
      rigid systems can now be considered a viable option in the lumbar degenerative
      disease, although clinical evaluations are necessary in the longer term.

PMID- 22402842
TI  - Treatment of kyphotic deformities in adults: our experience.
AB  - PURPOSE: Many degenerative phenomena frequently result into kyphotic lumbar and
      thoracic deformities or cause their progression combined with deformities on the
      frontal plane of the spine. In these patients, the progression of the sagittal
      imbalance may lead to a series of disabling functional and painful consequences.
      The analysis of the spinopelvic parameters biases the choice of the correction
      surgical strategy aimed at restoring a good tri-dimensional and sagittal balance
      of the spine. MATERIALS AND METHODS: Sample included 62 patients treated in our
      Operation Unit that were enrolled for evaluation; they were affected with
      prevailing sagittal deformities. RESULTS: Clinical results were evaluated through
      the administration of SF-36, Oswestry Disability Index (ODI), Roland Morris (RM),
      and visual analogical scale (VAS). CONCLUSIONS: In our experience, patients with
      sagittal imbalance and short fusion areas show a higher risk of correction loss;
      the arthrodesis area must include the thoracolumbar junction, and it is often
      necessary to include the whole thoracic spine in the arthrodesis area. This is to
      avoid any loss of correction, implants mobilization, and proximal hyperkyphosis.

PMID- 22402843
TI  - Transdiscal L5-S1 screws for the treatment of adult spondylolisthesis.
AB  - PURPOSE: The aim of the study was to evaluate clinical and radiographic outcome
      of patients treated with a modified Grob technique analysing the advantages
      related to increased mechanical stability. METHODS: 30 patients that underwent
      "in situ" fusion for L5-S1 spondylolisthesis were evaluated. All patients
      presented a low-dysplastic developmental L5-S1 spondylolisthesis. Patients were
      divided into two groups: A, in which L5-S1 pedicle instrumentation associated
      with transsacral screw fixation was performed, and B, in which L5-S1 pedicle
      instrumentation associated with a posterolateral interbody fusion (PLIF) was
      performed. RESULTS: Patients treated with transdiscal L5-S1 fixation observed a
      faster resolution of the symptoms and a more rapid return to daily activities,
      especially at 3-6 months' follow-up. The technique is reliable in giving an
      optimal mechanical stability to obtain a solid fusion. CONCLUSIONS: The
      advantages of this technique are lower incidence of neurologic complications,
      speed of execution and faster return to normal life.

PMID- 22402844
TI  - The metabolic basis of adolescent idiopathic scoliosis: 2011 report of the
      "metabolic" workgroup of the Fondation Yves Cotrel.
AB  - OBJECTIVE: The purpose of this review is to elucidate the metabolic processes
      involved in the pathogenesis of adolescent idiopathic scoliosis (AIS) in light of
      research by the present authors as well as current literature. METHODS:
      Pathogenetic mechanisms involved in AIS were modeled as (a) a form of
      neuromuscular scoliosis (in conjunction with an adverse mechanical environment
      such as bipedality), in which hormonal and other chemical factors act as
      regulators of skeletal muscle tone and function; (b) as a consequence of an
      abnormality in growth of the spinal column (in conjunction with an adverse
      mechanical environment such as bipedality), in which hormones and other chemical
      factors act as regulators of growth; and (c) as a mechanical failure of one side
      of the vertebral column due to a defect in trabecular formation or mineralization
      (in conjunction with an adverse mechanical environment such as bipedality); in
      which hormonal and other chemical factors act as regulators of bone formation,
      mineralization and/or resorption. RESULTS AND CONCLUSION: Current evidence
      supporting these models individually or in combination is discussed.

PMID- 22402845
TI  - [Process optimization in pediatric anesthesia-- fast-track: what is possible:
      what makes sense?].
AB  - Process optimization offers the opportunity to improve the quality and efficiency
      of medical care. Various approaches are possible in a pre-, peri- and
      postoperative care setting: It is almost always possible to prepare the children
      for surgery on an outpatient basis. This allows for hospital admission the same
      day or the evening before the procedure. But a schedule needs to be established
      that includes a certain leeway for admission and preoperative fasting in order to
      cater for a flexible response to delays or cancelations on the surgical list. An
      efficient use of theatre time can only be assured if several anesthetists can
      work in parallel. This applies in particular to complex anesthetic inductions.
      Sufficient staff and facilities are a prerequisite for this. The use of
      ultrasound for vascular access and regional anesthesia raises the success rate
      and saves time. In the postoperative period good analgesia with a fixed
      therapeutic regime, immediate postoperative feeding and mobilization improve the
      care.

PMID- 22402846
TI  - [Cardiac arrest and hypothermia caused by suicidal intoxication with butane: a
      case report].
AB  - In the emergency medicine field cases of intoxication by sniffing agents do not
      occur very often. Nevertheless, considering the easy availability of butane the
      option of abuse especially by adolescent persons cannot be ignored. Although many
      cases of accidental death caused by malignant arrhythmia are described ("Sudden
      sniffing death syndrome"), suicide attempts using butane are a rarity. In this
      case the emergency treatment has to allow for special pathophysiological changes
      explained by physicochemical characteristics of butane. The following case report
      describes the symptomatology and pre-hospital treatment of an intoxication by
      butane with a suicidal intention.

PMID- 22402847
TI  - [Hemodynamic monitoring - benefit or risk to the patient?].

PMID- 22402848
TI  - [Effects of advanced haemodynamic monitoring on perioperative outcome in high
      risk patients].
AB  - Advanced haemodynamic monitoring provides information on blood flow, volume
      status, and oxygen supply to demand ratio. Together with related therapeutic
      algorithms these variables can be used to optimize cardiac preload and oxygen
      delivery in the perioperative period. There is increasing evidence that a goal
      directed therapy can improve perioperative outcome. In this review we will
      briefly describe different target variables and their relevance for the
      haemodynamic optimization of high-risk surgical patients.

PMID- 22402849
TI  - [New aspects of minimally invasive cardiac output monitoring].
AB  - The variety of minimally invasive cardiac output (CO) monitoring devices is
      growing rendering it difficult to keep track of new developments. In this article
      technical principles, limitations and validation procedures considering new
      aspects are reviewed. An integrated approach for their use is proposed since no
      single device can comply with all clinical needs. CO should be interpreted in
      combination with clinical information and other hemodynamic parameters. It's
      evident that not the monitor per se, but only the protocol / therapy based on the
      hemodynamic data can improve patients outcome.

PMID- 22402850
TI  - [Is there any indication for perioperative use of the pulmonary artery
      catheter?].
AB  - The benefit of the pulmonary-artery catheter (PAC) is a matter of discussion
      since years. The development of alternative monitoring techniques especially for
      measurement of volume parameters has decreased routine use of the PAC. Several
      investigations verified advantages of therapy attempting to optimize circulation
      parameters regardless of the used technique. Nonetheless, patients with a higher
      peri-operative risk, especially in cardiovascular surgery, may benefit from PAC
      monitoring intra- or postoperatively.The concerns about the available monitoring
      techniques bear mainly on the fear being too invasive. Up to now, there is no
      technique complying with all requirements of an ideal monitoring system.

PMID- 22402851
TI  - A spectroscopic approach to monitor the cut processing in pulsed laser osteotomy.
AB  - During laser osteotomy surgery, plasma arises at the place of ablation. It was
      the aim of this study to explore whether a spectroscopic analysis of this plasma
      would allow identification of the type of tissue that was affected by the laser.
      In an experimental setup (Rofin SCx10, CO(2) Slab Laser, wavelength 10.6 MUm,
      pulse duration 80 MUs, pulse repetition rate 200 Hz, max. output in cw-mode 100
      W), the plasma spectra evoked by a pulsed laser, cutting 1-day postmortem pig and
      cow bones, were recorded. Spectra were compared to the reference spectrum of bone
      via correlation analysis. Our measurements show a clear differentiation between
      the plasma spectra when cutting either a bone or a soft tissue. The spectral
      changes could be detected from one to the next spectrum within 200 ms. Continuous
      surveillance of plasma spectra allows us to differentiate whether bone or soft
      tissue is hit by the last laser pulse. With this information, it may be possible
      to stop the laser when cutting undesired soft tissue and to design an automatic
      control of the ablation process.

PMID- 22402852
TI  - Roles of Ca2+ ions in the control of ChREBP nuclear translocation.
AB  - Carbohydrate-responsive element binding protein (ChREBP (MLXIPL)) is emerging as
      an important mediator of glucotoxity both in the liver and in the pancreatic beta
      cells. Although the regulation of its nuclear translocation and transcriptional
      activation by glucose has been the subject of intensive research, it is still not
      fully understood. We have recently uncovered a novel mechanism in the excitable
      pancreatic beta-cell where ChREBP interacts with sorcin, a penta-EF-hand Ca(2)(+)
      binding protein, and is sequestered in the cytosol at low glucose concentrations.
      Upon stimulation with glucose and activation of Ca(2)(+) influx, or application
      of ATP as an intracellular Ca(2)(+)-mobilising agent, ChREBP rapidly translocates
      to the nucleus. In sorcin-silenced cells, ChREBP is constitutively present in the
      nucleus, and both glucose and Ca(2)(+) are ineffective in stimulating further
      ChREBP nuclear shuttling. Whether an active Ca(2)(+)-sorcin element of ChREBP
      activation also exists in non-excitable cells is discussed.

PMID- 22402853
TI  - Intravenous thrombolysis in young stroke patients: results from the SITS-ISTR.
AB  - OBJECTIVE: To assess safety and efficacy of thrombolysis in 18- to 50-year-old
      patients compared to those aged 51 to 80 years recorded in the Safe
      Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis
      Register (SITS-ISTR). METHODS: A total of 27,671 patients aged 18-80 years
      treated with IV alteplase within 4.5 hours of symptom onset were enrolled in SITS
      ISTR between 2002 and 2010. Main outcome measures were symptomatic intracerebral
      hemorrhage (SICH; deterioration of >=4 points on the NIH Stroke Scale [NIHSS]
      within 24 hours and type 2 parenchymal hematoma), mortality, and functional
      independence (modified Rankin Scale [mRS] 0-2) at 3 months. RESULTS: In the 3,246
      (11.7%) patients aged 18-50, SICH occurred in 0.6% vs 1.9% in those aged 51-80
      (adjusted odds ratio [aOR] 0.53; 95% confidence interval [CI] 0.31-0.90, p =
      0.02). Three-month mortality was 4.9% and 14.4%, respectively (aOR 0.49; 95% CI
      0.40-0.60, p < 0.001) and functional independence was 72.1% vs 54.5%,
      respectively (aOR 1.61; 95% CI 1.43-1.80, p < 0.0001). In multivariable analysis
      in young patients, baseline systolic blood pressure (SBP) was the only
      independent factor associated with SICH (p = 0.04). Baseline NIHSS, baseline
      glucose, and signs of infarction in baseline imaging scan were associated with
      higher mortality and poorer functional outcome. Male gender, mRS before stroke,
      and atrial fibrillation (AF) were associated with higher mortality, and age, SBP,
      and previous stroke were associated with mRS. CONCLUSIONS: Treatment with IV
      alteplase is safe in young ischemic stroke patients and they benefit more
      compared to older patients. We found several factors associated with SICH,
      mortality, and functional outcome. These can be used to help in the selection of
      young ischemic stroke patients for thrombolysis. CLASSIFICATION OF EVIDENCE: This
      study provides Class III evidence that younger patients (18-50 years) with
      ischemic stroke symptoms treated with IV alteplase have lower morbidity and
      mortality compared to older patients (51-80 years).

PMID- 22402854
TI  - MS and heat: the smoke and the fire.

PMID- 22402855
TI  - Neuromyelitis optica and pregnancy.
AB  - OBJECTIVE: The purpose of our study was to assess the influence of pregnancy on
      the course of neuromyelitis optica (NMO) and the impact of epidural analgesia and
      breastfeeding on its activity in the postpartum period. METHODS: We performed a
      retrospective study of patients with NMO diagnosed according to Wingerchuk
      criteria. We noted the number of relapses during the year before pregnancy (BP),
      during pregnancy (first trimester, second trimester, third trimester), and the
      year after (Y + 1: first trimester, second trimester [PP2], and third and fourth
      trimesters postpartum). Epidural analgesia and breastfeeding were recorded.
      Disability was evaluated with the Kurtzke Expanded Disability Status Scale
      (EDSS). The annualized relapse rate (ARR) was calculated. RESULTS: We identified
      124 patients (85 female) in the French NOMADMUS cohort on November 1, 2010. A
      total of 20 women (including 25 pregnancies) were informative with complete
      files. Comparisons between the ARR of each period and BP (1.0 +/- 0.09) only
      showed an increased tendency for PP2 (0.8 +/- 0.06, p = 0.07). Epidural analgesia
      and breastfeeding had no influence on the course of NMO. The EDSS score increased
      from 1.5 +/- 1.7 BP to 2.6 +/- 1.9 Y + 1 (p = 0.027). CONCLUSION: This study
      shows that pregnancy influences the activity of NMO, a finding that justifies
      close medical monitoring. We found no evidence to suggest that either epidural
      analgesia or breastfeeding has an aggravating effect on NMO.

PMID- 22402856
TI  - Severe multiple sclerosis relapse under fingolimod therapy: incident or
      coincidence?

PMID- 22402857
TI  - Offspring number, pregnancy, and risk of a first clinical demyelinating event:
      the AusImmune Study.
AB  - OBJECTIVE: To examine the association between past pregnancy, offspring number,
      and first clinical demyelination risk. METHODS: Cases (n = 282) were aged 18-59
      years with a first clinical diagnosis of CNS demyelination (first clinical
      demyelinating event [FCD]) and resident within 1 of 4 Australian centers (from
      latitudes 27 degrees  south to 43 degrees  south) from 2003 to 2006. Controls (n
      = 542) were matched to cases on age, sex, and study region, without first
      clinical diagnosis of CNS demyelination. RESULTS: Higher offspring number was
      associated with FCD risk among women (p < 0.001) but not men (p = 0.71);
      difference in effect; p = 0.001. Among women, higher parity was associated with
      reduced risk of FCD (adjusted odds ratio 0.51 [95% confidence interval 0.36,
      0.72] per birth) with a similar magnitude of effect observed among classic first
      demyelinating events (adjusted odds ratio 0.47 [95% confidence interval 0.29,
      0.74]). The apparent beneficial effect of higher parity was also evident among
      parous women only (p < 0.001). Among cases, a clear female excess was evident for
      those with low but not high (4 or more) offspring number. Factors such as human
      leukocyte antigen DR15 genotype did not appear to modify the association between
      higher parity and a reduced FCD risk among women. CONCLUSIONS: These findings are
      consistent with a cumulative beneficial effect of pregnancy. Temporal changes
      toward an older maternal age of parturition and reduced offspring number may
      partly underlie the increasing female excess among MS cases over time.

PMID- 22402858
TI  - Treating PD axial signs with DBS: is two better than one?

PMID- 22402859
TI  - Combined pedunculopontine-subthalamic stimulation in Parkinson disease.
AB  - OBJECTIVE: To assess the effect of deep brain stimulation (DBS) in the
      pedunculopontine nucleus (PPN) and caudal zona incerta (cZi)-both separately and
      in combination-on motor symptoms and regional cerebral blood flow (rCBF) in
      patients with Parkinson disease (PD). METHODS: Four patients with bilateral cZi
      and PPN DBS electrodes were rated with the Unified Parkinson's Disease Rating
      Scale motor subscale (UPDRS-III) when taking and withdrawn from medication. A
      block of 16 [(15)O]-H(2)O PET resting measurements of rCBF were performed in 4
      different states with patients withdrawn from medication: 1) no stimulation, 2)
      cZi stimulation alone, 3) PPN stimulation alone, 4) combined PPN/cZi stimulation.
      RESULTS: When patients were medicated, combined PPN/cZi stimulation produced a
      statistically significant improvement in UPDRS-III score compared to cZi
      stimulation alone. In the "off" medication state, the clinical effect of combined
      stimulation was not significantly different from that induced by cZi stimulation
      alone. Concomitant PPN/cZi stimulation had a cumulative effect on levels of rCBF,
      effectively combining subcortical and cortical changes induced by stimulation of
      either target in isolation. CONCLUSIONS: These findings suggest that concomitant
      low frequency stimulation of PPN and cZi regions induces additive brain
      activation changes and provides improved control of PD symptoms when medicated.
      CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that
      concomitant low frequency stimulation of PPN and cZI improves motor symptoms in
      patients with PD on dopamine replacement. It provides Class III evidence that
      concomitant low frequency stimulation of PPN and cZi induces additive rCBF
      changes in motor areas of brain.

PMID- 22402860
TI  - Branch occlusive disease: clinical and magnetic resonance angiography findings.
AB  - BACKGROUND: We evaluated the clinicoradiologic characteristics of patients with
      branch occlusive disease (BOD)-type intracranial atherosclerotic stroke (ICAS)
      compared with those of patients with non-BOD-type ICAS or with small artery
      disease (SAD). METHODS: We analyzed 201 consecutive patients with acute infarcts
      within the middle cerebral artery (MCA) distribution but no demonstrable carotid
      or cardiac embolism sources. According to the diffusion-weighted imaging (DWI)
      distribution and the presence of ipsilateral MCA stenosis, of any degree, on
      magnetic resonance angiography (3-T MRI), we divided patients into 3 groups: 1)
      BOD: subcortical infarcts with MCA stenosis (n = 46); 2) non-BOD: infarcts beyond
      the subcortical area with MCA stenosis (n = 52); and 3) SAD (n = 103). We
      compared risk factors, degree of stenoses and distribution, and radiologic
      features of microangiopathy (leukoaraiosis and cerebral microbleeds) among the
      groups. RESULTS: Risk factor profiles were similar among the groups, except that
      hypertension and current smoking were more prevalent in the non-BOD than in the
      BOD group (p = 0.032 and 0.045). The relevant MCA had more severe and focal
      stenosis in the non-BOD than in the BOD group (stenosis of >=70%; 76.9% vs 28.3%;
      p < 0.001), but the degree of nonrelevant stenosis was similar across the groups.
      Although clinical features, DWI lesion patterns, and microangiopathy findings
      were similar between the BOD and SAD groups, nonrelevant stenosis was more
      prevalent in the BOD than in the SAD group (p < 0.01). CONCLUSIONS: BOD is
      prevalent (47% of ICAS) and shares common characteristics with non-BOD-type ICAS,
      although its clinicoradiologic features may resemble those of SAD. The
      morphologic characteristics of stenosis and risk factors may associate with a
      stroke phenotype in patients with ICAS.

PMID- 22402861
TI  - Warmer outdoor temperature is associated with worse cognitive status in multiple
      sclerosis.
AB  - OBJECTIVE: Patients with multiple sclerosis (MS) have more clinical exacerbations
      and T2 lesion activity during warmer weather. The current study is the first to
      investigate whether outdoor temperature is related to cognitive status across
      patients with MS (cross-sectional analysis), and whether cognitive status
      fluctuates with changes in outdoor temperature within patients with MS
      (longitudinal analysis). METHODS: For the cross-sectional analysis, 40 patients
      with MS and 40 healthy control (HC) subjects were recruited throughout the
      calendar year. Cognitive status (processing speed, memory) and outdoor
      temperature were recorded for the day of testing. We calculated partial
      correlations between cognitive status and temperature for patients with MS and
      HCs, controlling for demographic and disease variables. For the longitudinal
      analysis, cognitive status and outdoor temperature were recorded at baseline and
      6-month follow-up in a separate sample of 45 patients with MS. We calculated the
      partial correlation between temperature and cognitive status at follow-up,
      controlling for baseline temperature and cognitive status (i.e., whether
      temperature changes are related to cognitive changes within patients with MS).
      RESULTS: Cross-sectionally, warmer temperature was related to worse cognitive
      status in patients with MS (r(p) = -0.45, p = 0.006), not in HCs (r(p) = 0.00, p
      = 0.984). Longitudinally, increased outdoor temperature from baseline to follow
      up was related to a decline in cognitive status within patients with MS (r(p) = 
      0.39, p = 0.010). CONCLUSIONS: Cognitive status in patients with MS is worse on
      warmer days, consistent with a previously established link between heat and
      lesion activity. Our findings have implications for clinical trial planning,
      treatment, and lifestyle decisions. We discuss cognitive status as a potential
      marker of quiescent exacerbations.

PMID- 22402862
TI  - Eight new mutations and the expanding phenotype variability in muscular dystrophy
      caused by ANO5.
AB  - OBJECTIVE: Description of 8 new ANO5 mutations and significant expansion of the
      clinical phenotype spectrum associated with previously known and unknown
      mutations to improve diagnostic accuracy. METHODS: DNA samples of 101 patients in
      95 kindreds at our quaternary referral center in Finland, who had undetermined
      limb-girdle muscular dystrophy (LGMD), calf distal myopathy, or creatine kinase
      (CK) elevations of more than 2,000 IU/L, were selected for ANO5 genetic
      evaluation, and the clinical findings of patients with mutations were
      retrospectively analyzed. RESULTS: A total of 25 patients with muscular dystrophy
      caused by 11 different recessive mutations in the ANO5 gene were identified. The
      vast majority of mutations, 8 of 11, proved to be previously unknown new
      mutations. The most frequent mutation, c.2272C>T (p.R758C), was present in 20
      patients. The phenotypes associated with this and the common European mutation,
      c.191dupA, varied from nearly asymptomatic high hyperCKemia to severe LGMD with
      consistently milder phenotypes in female patients. CONCLUSIONS: Mutations in ANO5
      are a frequent cause of undetermined muscular dystrophy, with both distal and
      proximal presentation. Other types include high hyperCKemia, myalgia, or calf
      hypertrophy over decades without significant weakness, especially in female
      patients. Mutations are distributed all over the gene, indicating that muscular
      dystrophy caused by ANO5 can be expected to occur in all populations.

PMID- 22402863
TI  - Spectrum of cognitive impairment in neurocysticercosis: differences according to
      disease phase.
AB  - OBJECTIVES: Cognitive decline related to neurocysticercosis (NC) remains poorly
      characterized and underdiagnosed. In a cross-sectional study with a prospective
      phase, we evaluated cognitive decline in patients with strictly calcified form (C
      NC), the epidemiologically largest subgroup of NC, and investigated whether there
      is a spectrum of cognitive abnormalities in the disease. METHODS: Forty treatment
      naive patients with C-NC aged 37.6 +/- 11.3 years and fulfilling criteria for
      definitive C-NC were submitted to a comprehensive cognitive and functional
      evaluation and were compared with 40 patients with active NC (A-NC) and 40
      healthy controls (HC) matched for age and education. Patients with dementia were
      reassessed after 24 months. RESULTS: Patients with C-NC presented 9.4 +/- 3.1
      altered test scores out of the 30 from the cognitive battery when compared to HC.
      No patient with C-NC had dementia and 10 patients (25%) presented cognitive
      impairment-no dementia (CIND). The A-NC group had 5 patients (12.5%) with
      dementia and 11 patients (27.5%) with CIND. On follow-up, 3 out of 5 patients
      with A-NC with dementia previously still presented cystic lesions with scolex on
      MRI and still had dementia. One patient died and the remaining patient no longer
      fulfilled criteria for either dementia or CIND, presenting exclusively calcified
      lesions on neuroimaging. CONCLUSIONS: Independently of its phase, NC leads to a
      spectrum of cognitive abnormalities, ranging from impairment in a single domain,
      to CIND and, occasionally, to dementia. These findings are more conspicuous
      during active vesicular phase and less prominent in calcified stages.

PMID- 22402865
TI  - Pregnancy: a "modifiable" risk factor in MS?

PMID- 22402864
TI  - Pentoxifylline as a rescue treatment for DMD: a randomized double-blind clinical
      trial.
AB  - OBJECTIVE: To determine whether pentoxifylline (PTX) slows the decline of muscle
      strength and function in ambulatory boys with Duchenne muscular dystrophy (DMD).
      METHODS: This was a multicenter, randomized, double-blinded, controlled trial
      comparing 12 months of daily treatment with PTX or placebo in corticosteroid
      treated boys with DMD using a slow-release PTX formulation (~20 mg/kg/day). The
      primary outcome was the change in mean total quantitative muscle testing (QMT)
      score. Secondary outcomes included changes in QMT subscales, manual muscle
      strength, pulmonary function, and timed function tests. Outcomes were compared
      using Student t tests and a linear mixed-effects model. Adverse events (AEs) were
      compared using the Fisher exact test. RESULTS: A total of 64 boys with DMD with a
      mean age of 9.9 +/- 2.9 years were randomly assigned to PTX or placebo in 11
      participating Cooperative International Neuromuscular Research Group centers.
      There was no significant difference between PTX and the placebo group in total
      QMT scores (p = 0.14) or in most of the secondary outcomes after a 12-month
      treatment. The use of PTX was associated with mild to moderate gastrointestinal
      or hematologic AEs. CONCLUSION: The addition of PTX to corticosteroid-treated
      boys with DMD at a moderate to late ambulatory stage of disease did not improve
      or halt the deterioration of muscle strength and function over a 12-month study
      period. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that
      treatment with PTX does not prevent deterioration in muscle function or strength
      in corticosteroid-treated boys with DMD.

PMID- 22402866
TI  - Autoantibodies and high-risk HLA susceptibility markers in first-degree relatives
      of Brazilian patients with type 1 diabetes mellitus: a progression to disease
      based study.
AB  - PURPOSE: The objective of this study was to determine the frequencies of
      autoantibodies to heterogeneous islet-cell cytoplasmic antigens (ICA), glutamic
      acid decarboxylase(65) (GAD(65)A), insulinoma-associated antigen-2 (IA-2A) and
      insulin (IAA)-and human leukocyte antigen (HLA) class II markers (HLA-DR and -DQ)
      in first degree relatives of heterogeneous Brazilian patients with type I
      diabetes (T1DM). A major focus of this study was to determine the influence of
      age, gender, proband characteristics and ancestry on the prevalence of
      autoantibodies and HLA-DR and -DQ alleles on disease progression and genetic
      predisposition to T1DM among the first-degree relatives. METHODS: IAA, ICA,
      GAD(65)A, IA-2A and HLA- class II alleles were determined in 546 first-degree
      relatives, 244 siblings, 55 offspring and 233 parents of 178 Brazilian patients
      with T1DM. RESULTS: Overall, 8.9% of the relatives were positive for one or more
      autoantibodies. IAA was the only antibody detected in parents. GAD(65) was the
      most prevalent antibody in offspring and siblings as compared to parents and it
      was the sole antibody detected in offspring. Five siblings were positive for the
      IA-2 antibody. A significant number (62.1%) of siblings had 1 or 2 high risk HLA
      haplotypes. During a 4-year follow-up study, 5 siblings (expressing HLA-DR3 or 
      DR4 alleles) and 1 offspring positive for GAD(65)A progressed to diabetes.
      CONCLUSIONS: The data indicated that the GAD(65) and IA-2 antibodies were the
      strongest predictors of T1DM in our study population. The high risk HLA
      haplotypes alone were not predictive of progression to overt diabetes.

PMID- 22402867
TI  - A new cascade reaction: concurrent construction of six and five membered rings
      leading to novel fused quinazolinones.
AB  - A one-pot cascade reaction has been developed leading to the concurrent
      construction of six and five membered fused N-heterocyclic rings of indazolo[3,2
      b]quinazolinones. The methodology involved the reaction of isatoic anhydride, a
      hydrazine and o-iodo benzaldehyde in the presence of Pd(PPh(3))(4) and BINAP in
      MeCN. The mechanism of this cascade reaction is discussed. A variety of
      indazolo[3,2-b]quinazolinone derivatives were prepared by using this methodology
      in good yields, some of which were tested for their PDE4 inhibitory properties in
      vitro. The dose response and docking study performed using a representative
      compound is presented.

PMID- 22402868
TI  - Simultaneous neoadjuvant radiochemotherapy with capecitabine and oxaliplatin for
      locally advanced rectal cancer. Treatment outcome outside clinical trials.
AB  - BACKGROUND: Phase II trials of neoadjuvant treatment in UICC-TNM stage II and III
      rectal cancer with capecitabine and oxaliplatin demonstrated favourable rates on
      tumour regression with acceptable toxicity. PATIENTS AND METHODS: Retrospective
      evaluation of 34 patients treated from 2005-2008 outside clinical trials (CTR)
      with neoadjuvant irradiation (45-50.4 Gy) and simultaneous capecitabine 825
      mg/m(2) b.i.d. on days 1-14 and 22-35 and oxaliplatin 50 mg/m(2) on days 1, 8, 22
      and 29 (CAPOX). Twenty-six (77%) patients received one or two courses of
      capecitabine 1,000 mg/m(2) b.i.d. on days 1-14 and oxaliplatin 130 mg/m(2) on day
      1 (XELOX) prior to simultaneous chemoradiotherapy. RESULTS: UICC-TNM stage
      regression was observed in 60% (n = 20). Dworak's regression grades 3 and 4 were
      achieved in 18.2% (n = 6) and 15.1% (n = 5) of the patients. Sphincter-preserving
      surgery was performed in 53% (n = 8) of patients with a tumour of the lower
      rectum. Within the mean observation of 24 months, none of the patients relapsed
      locally, 1 patient had progressive disease and 5 patients (15%) relapsed
      distantly. Toxicity of grade 3 and 4 was mainly diarrhoea 18% (n = 6) and
      perianal pain 9% (n = 3). Nevertheless, severe cardiac events (n = 2), severe
      electrolyte disturbances (n = 2), and syncopes (n = 2) were observed as well.
      CONCLUSION: Treatment efficacy and common toxicity are similar to the reports of
      phase I/II trials. However, several severe adverse events were observed in our
      cohort study. The predisposing factors for these events have yet to be studied
      and may have implications for the selection of patients outside CTR.

PMID- 22402869
TI  - Postoperative chemoradiotherapy for gallbladder cancer.
AB  - PURPOSE: The goal of this work was to analyze the outcome of adjuvant
      chemoradiotherapy for patients with gallbladder cancer who underwent surgical
      resection and to identify the prognostic factors for these patients. PATIENTS AND
      METHODS: Between August 1989 and November 2006, 47 patients with gallbladder
      cancer underwent surgical resection followed by adjuvant radiotherapy. There were
      21 males and 26 females, and median age was 60 years (range 44-75 years).
      Postoperative radiotherapy was delivered to the tumor bed and regional lymph
      nodes up to 40-50 Gy at 2 Gy/fraction; 41 patients also received intravenous 5
      fluorouracil as a radiosensitizer. Median follow-up duration was 48 months for
      survivors. RESULTS: There were 2 isolated locoregional recurrences, 14 isolated
      distant metastases, and 7 combined locoregional and distant relapses. The 5-year
      overall survival rate was 43.7%. According to the extent of resection, the 5-year
      overall survival rates were 52.8%, 20.0%, and 0% in R0-, R1-, and R2-resected
      patients, respectively (p = 0.0038). On multivariate analysis incorporating
      extent of resection, T stage, N stage, performance of lymph node dissection, and
      histologic differentiation, extent of resection was the only prognostic factor
      associated with overall survival (p = 0.0075). Among the 37 patients with R0
      resection, there was no difference of 5-year overall survival rates in patients
      with N0, N1, and Nx diseases (46.2%, 60.0%, and 44.4%, respectively, p = 0.6246).
      As for significant treatment-related morbidity, there was only 1 patient with
      grade 4 gastric ulcer. CONCLUSION: Adjuvant chemoradiotherapy after R0 resection
      can achieve a good long-term survival rate in gallbladder cancer patients, even
      in those with lymph node metastases, and may play a role for patients who
      underwent R0 resection of primary tumor without lymph node dissection.

PMID- 22402870
TI  - Chest wall radiotherapy with volumetric modulated arcs and the potential role of
      flattening filter free photon beams.
AB  - PURPOSE: The goal of the work was to assess the role of RapidArc treatments in
      chest wall irradiation after mastectomy and determine the potential benefit of
      flattening filter free beams. METHODS AND MATERIAL: Planning CT scans of 10 women
      requiring post-mastectomy chest wall radiotherapy were included in the study. A
      dose of 50 Gy in 2 Gy fractions was prescribed. Organs at risk (OARs) delineated
      were heart, lungs, contralateral breast, and spinal cord. Dose-volume metrics
      were defined to quantify the quality of concurrent treatment plans assessing
      target coverage and sparing of OARs. Plans were designed for conformal 3D therapy
      (3DCRT) or for RapidArc with double partial arcs (RA). RapidArc plans were
      optimized for both conventional beams as well as for unflattened beams (RAF). The
      goal for this planning effort was to cover 100% of the planning target volume
      (PTV) with >= 90% of the prescribed dose and to minimize the volume inside the
      PTV receiving > 105% of the dose. The mean ipsilateral lung dose was required to
      be lower than 15 Gy and V(20 Gy) < 22%. Contralateral organ irradiation was
      required to be kept as low as possible. RESULTS: All techniques met planning
      objectives for PTV and for lung (3DCRT marginally failed for V(20 Gy)). RA plans
      showed superiority compared to 3DCRT in the medium to high dose region for the
      ipsilateral lung. Heart irradiation was minimized by RAF plans with ~4.5 Gy and
      ~15 Gy reduction in maximum dose compared to RA and 3DCRT, respectively. RAF
      resulted in superior plans compared to RA with respect to contralateral breast
      and lung with a reduction of ~1.7 Gy and 1.0 Gy in the respective mean doses.
      CONCLUSION: RapidArc treatment resulted in acceptable plan quality with superior
      ipsilateral tissue sparing compared to traditional techniques. Flattening filter
      free beams, recently made available for clinical use, might provide further
      healthy tissue sparing, particularly in contralateral organs, suggesting their
      applicability for large and complex targets.

PMID- 22402871
TI  - Increased expression of FAT10 is correlated with progression and prognosis of
      human glioma.
AB  - FAT10, as a small ubiquitin-like modifier, plays an important role in various
      cellular processes, including mitosis, immune response, and apoptosis, the dys
      regulation of which may arise tumorigenesis. Therefore, the aim of this study was
      to examine the expression of FAT10 at gene and protein levels in glioma samples
      with different WHO grades and its association with survival. One hundred and
      twenty-eight glioma specimens and 10 non-neoplastic brain tissues were collected.
      Immunohistochemistry assay, quantitative real-time PCR and Western blot analysis
      were carried out to investigate the expression of FAT10. Kaplan-Meier method and
      Cox's proportional hazards model were used in survival analysis.
      Immunohistochemistry showed that FAT10 protein was over-expressed in glioma
      tissues. FAT10 mRNA and protein levels were both higher in glioma compared to
      control on real-time PCR and Western blot analysis (both P < 0.001).
      Additionally, its expression levels increase from grade I to grade IV glioma
      according to the results of real-time PCR, immunohistochemistry analysis and
      Western blot. Moreover, the survival rate of FAT10-positive patients was
      significantly lower than that of FAT10-negative patients (P < 0.001). We further
      confirmed that the increased expression of FAT10 was a significant and
      independent prognostic indicator in glioma by multivariate analysis (P < 0.001).
      Our data provides convincing evidence for the first time that the increased
      expression of FAT10 at gene and protein levels is correlated with poor outcome in
      patients with glioma. FAT10 may promote the aggressiveness of glioma and may be a
      potential prognosis predictor of glioma.

PMID- 22402872
TI  - Development and validation of a postmortem radiological alteration index: the RA
      Index.
AB  - This study aimed to derive an index quantifying the state of alteration of
      cadavers by quantifying the presence of gas in the body using postmortem
      multidetector computed tomography (MDCT) imaging, and to validate the index by
      defining its sensitivity and specificity. The RA (radiological alteration)-index
      was derived from postmortem MDCT data from 118 nontraumatically deceased people.
      To validate the index, 100 additional scanned bodies (50 % traumatically
      deceased) were retrospectively examined by two independent observers. Presence of
      gas at 82 sites was assessed by a radiologist, whereas a forensic pathologist
      only investigated the seven sites used for the RA-index. The RA-index was highly
      correlated to the overall presence of gas in all 82 sites (R(2) = 0.98 in the
      derivation set and 0.85 in the validation set). Semiquantitative evaluation of
      gas presence in each site showed moderate reliability (Cohen's kappa range, 0.41
      0.78); nevertheless, the overall RA-index was very reliable (ICC(2,1) = 0.95; 95
      % CI 0.92-0.96). Examiner using the RA-index detected heart cavities full of gas
      with a sensitivity of 100 % (95 % CI 51.7-100) and a specificity of 98.8 % (92.6
      99.9). We conclude that determining the presence of gas at seven sites is a valid
      means to measure the distribution of gas due to cadaveric alteration in the
      entire body. The RA-index is rapid, easy-to-use, and reliable for nonexperienced
      users, and it is a valid method to suspect the normal presence of gas from
      cadaveric alteration. MDCT can be used to screen for gas embolism and to give
      indications for gas composition analysis (gas chromatography).

PMID- 22402873
TI  - Chimerism in DNA of buccal swabs from recipients after allogeneic hematopoietic
      stem cell transplantations: implications for forensic DNA testing.
AB  - We attempted to quantitatively determine the chimeric state in a total of 162
      buccal swabs from 77 adult recipients aged 19-74 (median 50 years) after
      allogeneic hematopoietic cell transplantation by estimating the chimeric
      recipient/donor DNA ratios through analysis of 15 autosomal short tandem repeat
      markers. From each individual between one and nine, buccal swabs were taken at
      known time intervals after transplantation, ranging from 17 to 3,361 days (median
      394 days). In buccal cells, the determined recipient/donor DNA ratios turned out
      to be highly variable between individuals and also within an individual. Relative
      donor chimerism levels (%Ch) between 0 and 100 % were detected with maximal
      frequencies between 10 and 30 %. Blood was always found to show the donor's
      genotype while hair samples in all cases gave the recipient's genotype. We
      examine chimerism levels with respect to age, gender, and posttransplantation
      period and discuss the results in the context of forensic identity testing.

PMID- 22402874
TI  - Detection of genetic variation in KCNQ1 gene by high-resolution melting analysis
      in a prospective-based series of postmortem negative sudden death: comparison of
      results obtained in fresh frozen and formalin-fixed paraffin-embedded tissues.
AB  - High-resolution melting (HRM) analysis is a recently developed molecular
      technique proved to be applicable for detection of genetic variation, notably in
      sudden cardiac death. In certain circumstances, especially in postmortem genetic
      investigations, the formalin-fixed and paraffin-embedded (FFPE) tissues are the
      only DNA source available. The present study aimed to develop HRM assays,
      optimized for the analysis of FFPE tissues, to detect sequence variations in
      KCNQ1 exons in a prospective population-based series of postmortem negative
      sudden death and to compare the results between the paired freshly frozen and
      FFPE tissue samples simultaneously obtained from the same case. The analyses were
      conducted in each case of sudden death involving cases younger than 35 years with
      no significant morphological anomalies particularly with no cardiac structural
      disease and with negatives toxicological investigations. HRM analysis was
      successfully optimized for 13 of the 16 exons of the KCNQ1 gene. All mutated
      samples were correctly identified by HRM whatever the type of tissue tested.
      However, for FFPE samples, HRM indicated more positive samples than classical
      sequencing, used in parallel, due to the degradation of DNA by formalin fixation.
      This is the first postmortem study of KCNQ1 mutation detection with HRM on DNA
      extracted from FFPE samples with adapted protocol. Despite the false-positive
      detection, we concluded that the use of HRM as a screening method with FFPE
      samples to analyze KCNQ1 mutations can reduce the number of sequencing reactions
      and, thus, results in substantial time and cost savings.

PMID- 22402875
TI  - Treatment of intra-cranial aneurysms with the SILK flow diverter: 2 years'
      experience with 28 patients at a single center.
AB  - BACKGROUND: Flow diverters are recently developed stent-like endovascular devices
      developed to treat complex and non-coilable aneurysms. SILK is a type of flow
      diverter that has been used for nearly 3 years. Only sparse data about it are
      available. We would like to share our experience with this device. METHODS:
      Twenty-eight patients were treated with SILK from October 2008 to October 2010.
      Thirty-one treatment sessions were performed for 32 aneurysms using 31 SILKs.
      Twenty have been treated with SILK only and eight with SILK and adjuvant stents.
      Twenty-six (86%) patients performed cross-sectional imaging (MRA/CTA) for follow
      up. Eighteen (64%) patients had follow-up brain angiography. RESULTS: In all
      patients the SILK could be deployed. No case of early or late aneurysmal rupture
      was noted. Five patients (17.8%) developed immediate clinical complications,
      which were permanent in three (10.7%). All the complications occurred in patients
      harboring aneurysms larger than 15 mm. In two other patients, occlusion of the
      SILK was noted with no clinical deficit. A complete or near-complete aneurysmal
      occlusion was found in brain angiography or cross-sectional imaging follow-up in
      83.3% of the patients. CONCLUSIONS: SILK is a relatively simple device to use,
      with a low rate of technical and clinical complications and a high short-term
      aneurysmal occlusion rate. In aneurysms smaller than 15 mm, the results are
      excellent. Results are also encouraging in the larger aneurysms, taking into
      consideration their complexity. The device characteristics and mainly its
      drawbacks must be well known by the users.

PMID- 22402876
TI  - Surgical results of an endoscopic endonasal approach for clival chordomas.
AB  - BACKGROUND: The surgical approaches for clival chordomas remain controversial,
      although the extent of resection is one of the most important factors for long
      survival rates. Recently an endoscopic endonasal approach in good collaboration
      with otolaryngologists has attracted major attention as a surgical approach for
      clival chordomas. We describe our experience with the endoscopic endonasal
      approach and provide a review of the literature. METHODS: Between 2008 and 2011,
      six operations were performed via the endoscopic endonasal approach for clivus
      chordomas. The mean tumor size was 35 mm in diameter. The tumor location was
      mainly from the upper to middle clivus. The tumor extended into the cavernous
      sinus in five cases and intradurally in three cases. A binostril approach was
      performed in four cases, while a one nostril approach was performed in two cases.
      RESULTS: Gross total removal was achieved in three cases. The analysis of cases
      with incomplete resection suggested that residual tumors were observed epidurally
      and subdurally. The residual on the epidura was observed from the posterior
      clinoid to the posterior compartment of the cavernous sinus. On the other hand,
      the residual on the subdural was observed behind the upper part of the pituitary
      gland. There was no postoperative cerebrospinal fluid (CSF) leakage using
      vascularized nasoseptal flaps in any of the cases. CONCLUSIONS: The endoscopic
      endonasal transclival approach allows an appropriate extent of resection with
      acceptable complication rates in comparison with other approaches. In our series,
      the accomplishment of gross total removal was associated with the relationship
      between the tumors and surrounding structures, such as the pituitary gland and
      the cavernous portion of the intracranial carotid artery (ICA).

PMID- 22402877
TI  - Decompressive craniectomies, facts and fiction: a retrospective analysis of 526
      cases.
AB  - BACKGROUND: The aim of this article was to review the clinical practice of "bone
      flap decompression" in Regional Neurosurgical Units with no particular protocol
      in use. METHODS: From January 2005 to December 2008, a retrospective and
      multicentre study was conducted on patients who were treated with decompressive
      craniectomy (DC) in seven departments of neurosurgery in Italy. This study
      included patients with traumatic brain injury, stroke, aneurysmal subarachnoid
      haemorrhage and cerebral arteriovenous malformations. Data were retrieved from
      individual medical records. RESULTS: We identified 526 patients with DC. Age was
      the most significant predictor factor of survival, together with pupil
      reactivity, time of decompression and size of the bone flap. The effect of age in
      predicting survival was so important that in patients over 65 years old we did
      not find any other significant factor related to survival. In younger patients,
      the survival rate was much better with a large bone flap (p = 0.01).
      Unfortunately, 57% of patients were decompressed with a bone flap of less than 12
      cm in diameter. This was probably due to the association in 80% of cases between
      haematoma evacuation and decompression. CONCLUSIONS: The current practice in many
      centres is different from published papers. Decompression is common over the age
      of 65 years, is associated with haematoma evacuation and often the bone flaps are
      inadequate in terms of size.

PMID- 22402878
TI  - A case of late-onset multiple sclerosis mimicking glioblastoma and displaying
      intraoperative 5-aminolevulinic acid fluorescence.

PMID- 22402879
TI  - MUTYH associated polyposis coli: one common and one rare mutation.

PMID- 22402880
TI  - Induction of human humoral immune responses in a novel HLA-DR-expressing
      transgenic NOD/Shi-scid/gammacnull mouse.
AB  - Mounting evidence has demonstrated that NOD-Shi/scid/gammac(null) (NOG) mice are
      one of the most suitable mouse strains for humanized mouse technologies, in which
      various human cells or tissues can be engrafted without rejection and
      autonomously maintained. We have characterized and analyzed various features of
      the human immune system reconstituted in NOG mice by transplanting human
      hematopoietic stem cells (hu-HSC). One of the problems of the quasi-immune system
      in these hu-HSC NOG mice is that the quality of immune responses is not always
      sufficient, as demonstrated by the lack of IgG production in response to antigen
      challenge. In this study, we established a novel transgenic NOG sub-strain of
      mice bearing the HLA-DRA and HLA-DRB1:0405 genes, which specifically expresses
      HLA-DR4 molecules in MHC II-positive cells. This mouse strain enabled us to match
      the haplotype of HLA-DR between the recipient mice and human donor HSC. We
      demonstrated that T-cell homeostasis was differentially regulated in HLA-matched
      hu-HSC NOG mice compared with HLA-mismatched control mice, and antibody class
      switching was induced after immunization with exogenous antigens in HLA-matched
      mice. This novel mouse strain improves the reconstituted human immune systems
      that develop in humanized mice and will contribute to future studies of human
      humoral immune responses.

PMID- 22402881
TI  - Glutathione-mediated alleviation of chromium toxicity in rice plants.
AB  - A hydroponic experiment was conducted to determine the possible effect of
      exogenous glutathione (GSH) in alleviating chromium (Cr) stress through examining
      plant growth, chlorophyll contents, antioxidant enzyme activity, and lipid
      peroxidation in rice seedlings exposed to Cr toxicity. The results showed that
      plant growth and chlorophyll content were dramatically reduced when rice plants
      were exposed to 100 MUM Cr. Addition of GSH in the culture solution obviously
      alleviated the reduction of plant growth and chlorophyll content. The activities
      of some antioxidant enzymes, including superoxide dismutase, catalase (CAT) and
      glutathione reductase in leaves, and CAT and glutathione peroxidase in roots
      showed obvious increase under Cr stress. Addition of GSH reduced malondialdehyde
      accumulation and increased the activities of these antioxidant enzymes in both
      leaves and roots, suggesting that GSH may enhance antioxidant capacity in Cr
      stressed plants. Furthermore, exogenous GSH caused significant decrease of Cr
      uptake and root-to-shoot transport in the Cr-stressed rice plants. It can be
      assumed that GSH is involved in Cr compartmentalization in root cells.

PMID- 22402882
TI  - Particle-induced X-ray emission analysis of elements in plasma from wild and
      captive sea turtles (Eretmochelys imbricata, Chelonia mydas, and Caretta caretta)
      in Okinawa, Japan.
AB  - The aim of this study was to evaluate the reliability of direct determination of
      trace and major element concentrations in plasma samples from wild (six
      hawksbill, nine green, and nine loggerhead) and captive sea turtles (25
      howksbill, five green, and three loggerhead) in Okinawa, Japan. The particle
      induced X-ray emission method allowed detection of 23 trace and major elements
      (Al, As, Br, Ca, Cl, Cr, Cu, Fe, Hg, K, Mg, Mn, Mo, Ni, P, Pb, S, Se, Si, Sr, Ti,
      Y, and Zn). The wild sea turtles were found to have high concentrations of As and
      Pb in plasma compared with captive, but there were no significant changes in the
      Al and Hg concentrations. Loggerhead sea turtles were found to have significantly
      higher accumulation of As and Pb in plasma in comparison to other species. These
      findings may be useful when adjusting environmental and species-related factors
      in severely polluted marine ecosystems. Our results indicate that measuring the
      plasma As and Pb concentrations in wild sea turtles might be of help to assess
      the level of pollution in marine ecosystems, keeping in mind that loggerhead sea
      turtles had been shown to have higher levels of As and Pb in plasma.

PMID- 22402883
TI  - Effects of dietary manganese on Cu, Fe, Zn, Ca, Se, IL-1beta, and IL-2 changes of
      immune organs in cocks.
AB  - Manganese (Mn) is an essential trace element required for normal development and
      bodily function. However, little is known about the effect of excessive amounts
      of Mn in immune organs of poultry. The aim of this study was to investigate the
      effect of dietary Mn on the content of trace elements, such as copper (Cu), iron
      (Fe), zinc (Zn), calcium (Ca), and selenium (Se), and the mRNA level of IL-1beta
      and IL-2 in immune organs (spleen, thymus, and bursa of Fabricius) and the
      content of IL-1beta and IL-2 in serum of poultry. Fifty-day-old male Hyline cocks
      were fed either a commercial diet or a Mn-supplemented diet containing 600, 900,
      and 1,800 mg/kg. The immune organs were collected at 30, 60, and 90 days,
      respectively, and the content of trace elements and the mRNA level of IL-1beta
      and IL-2 were examined; the serum were collected and the IL-1beta and IL-2
      contents detected. The results showed that Mn content in immune organs increased
      and Fe, Zn, and Ca contents decreased; however, Cu and Se contents showed no
      difference. IL-1beta and IL-2 mRNA levels and IL-1beta and IL-2 contents
      decreased. The present study demonstrates that excess exposure to Mn results in
      metal accumulations in immune organs. Manganism can disturb the balance of trace
      elements in immune organs and induce immune suppression in the molecular level;
      therefore, the immune function of cocks are also suppressed after manganism.

PMID- 22402885
TI  - VEGF, PF4 and PDGF are elevated in platelets of colorectal cancer patients.
AB  - Platelets sequester angiogenesis regulatory proteins which suggests an avenue for
      developing biomarkers to monitor disease. We describe a comparison of
      angiogenesis regulatory proteins found in platelets of colorectal cancer patients
      and normal controls. Platelet and plasma content of vascular endothelial growth
      factor (VEGF), basic fibroblast growth factor (bFGF), platelet derived growth
      factor (PDGF), platelet factor 4 (PF4), thrombospondin-1 (TSP-1) and endostatin
      in 35 patients with colon cancer were compared with 84 age-matched healthy
      controls using ELISAs. We standardized the platelet preparation procedure,
      introduced process controls and normalized the respective protein levels to
      platelet numbers using an actin ELISA. Statistically significant differences were
      found in the median levels of VEGF, PF4 and PDGF in platelets of patients with
      cancer compared to healthy individuals. Platelet concentrations in cancer
      patients versus controls were: VEGF 1.3 versus 0.6 pg/10(6), PF4 18.5 versus 9.4
      ng/10(6), and PDGF 34.1 versus 21.0 pg/10(6). Multivariable logistic regression
      analysis indicated that PDGF, PF4 and VEGF were independent predictors of
      colorectal carcinoma and as a set provided statistically significant
      discrimination (area under the curve = 0.893, P < .0001). No significant
      differences were detected for bFGF, endostatin, or TSP-1. Reference Change Value
      analysis determined that the differences seen were not clinically significant.
      Plasma levels yielded no correlations.

PMID- 22402886
TI  - Early evaluation of neoadjuvant chemotherapy response using FDG-PET/CT predicts
      survival prognosis in patients with head and neck squamous cell carcinoma.
AB  - BACKGROUND: The purpose of this study was to investigate the possibility of early
      survival prediction after completion of one cycle of neoadjuvant chemotherapy
      (NAC) by positron emission tomography (PET)/computed tomography (CT) with (18)F
      fluorodeoxyglucose (FDG). METHODS: Fifty-seven patients with advanced head and
      neck squamous cell carcinoma (HNSCC) underwent FDG-PET/CT scans twice, before and
      after one cycle of NAC. We calculated the maximal standardized uptake value
      (SUV(max)) for a primary tumor and/or metastatic lymph nodes and defined
      %decrease as the %difference in SUV(max) between the two scans divided by that of
      the initial scan. Patients were classified as responders by PET (%decrease
      >=55.5% or post-NAC SUV(max) <=3.5) and by RECIST (>=30% decrease in size). The
      local control (LC) rate and the disease-specific survival (DSS) rate were
      assessed between the responders and non-responders. Multivariate analysis was
      also performed using the Cox proportional hazards model. RESULTS: In univariate
      analysis, the PET finding of a primary site was a significant risk factor for LC
      and DSS rates at 2 years after completion of NAC (P = 0.03 and 0.02,
      respectively), but there was no difference between responders and non-responders
      by the RECIST criteria. In a multivariate regression analysis, the PET finding in
      the primary site and the definitive therapy choice were independent prognostic
      factors in LC, while the PET finding in the primary site was the only independent
      prognostic factor in DSS. CONCLUSION: Our preliminary data indicate that the PET
      finding in the primary lesion after one cycle of NAC was an independent
      prognostic factor in LC and DSS in patients with HNSCC.

PMID- 22402887
TI  - Sentinel lymph node biopsy for cutaneous melanoma: results of 10 years'
      experience in two regional training hospitals in the Netherlands.
AB  - BACKGROUND AND OBJECTIVE: The Multicenter Selective Lymphadenectomy Trial (MSLT
      I) demonstrated that the sentinel node (SN) status in cutaneous melanoma affects
      prognosis and that completion lymphadenectomy in SN-positive patients may improve
      survival. Our objective was to evaluate sentinel lymph node biopsy (SLNB) in two
      regional hospitals in the Netherlands. METHODS: Patients with localized melanoma
      were planned for wide excision and SLNB. Completion lymphadenectomy was
      recommended for positive SN status. Data were compared with the MSLT-I. RESULTS:
      A median of 2 (1-7) SNs were identified in 305 patients and complications
      occurred in 11%. Fifty-four patients (18%) demonstrated SN metastases and 45
      underwent completion lymphadenectomy (20% additional metastases). Six patients
      with initially negative SN developed lymph node metastases (sensitivity 90%).
      Overall disease-free survival was 83% (SN-negative 91% vs. SN-positive 41%; p <
      0.001) and melanoma-specific survival was 93% (SN-negative 97% vs. SN-positive
      62%; p < 0.001). Multivariate regression analysis revealed the SN status to be
      the most significant predictor for recurrence and melanoma-related death.
      CONCLUSION: Our results of SLNB are comparable to data from high-volume centers
      participating in MSLT-I. From a patient perspective, the false-negative SN rate
      of 10% and complication rate of 11% should be weighed against being informed
      about prognosis and having a possible therapeutic benefit from completion
      lymphadenectomy.

PMID- 22402888
TI  - Spatial complexity and spectral distribution variability of atrial activity in
      surface ECG recordings of atrial fibrillation.
AB  - Considerable research effort has been devoted to the estimation of the degree of
      organisation of atrial fibrillation (AF), to potentially support clinical
      decision making. The aims of this study were to: (1) analyse the temporal
      variability of spatial organisation (complexity) and spectral distribution of AF
      in body surface potential maps (BSPM), proposing an automated implementation of
      the analysis and (2) assess the applicability to reduced lead-sets. Twenty-one
      persistent AF recordings of 3 min each (64 BSPM: 32 anterior, 32 posterior) were
      analysed. The relationship between spatial organisation (C) and its variability
      (CV) was quantified on automatically delineated TQ segments. The relationship
      between spectral concentration (SC) and spectral variability (SV) was quantified
      on the atrial activity (AA) extracted using principal component analysis. Three
      different lead-sets: 64, 32 anterior and 10 anterior channels were considered.
      Significant (p < 0.001) correlation (rho) was found: rho(CV, C) >= 0.80, rho(SC,
      SV) <=-0.83 for all lead-sets. The results suggest that a higher degree of
      spatial organisation is associated with reduced variability of spatial
      organisation over time, and lower spectral variability associated with more
      prominent spectral peak in the AF frequency band (4-10 Hz).

PMID- 22402889
TI  - Automated segmentation of comet assay images using Gaussian filtering and fuzzy
      clustering.
AB  - Comet assay is one of the most popular tests for the detection of DNA damage at
      single cell level. In this study, an algorithm for comet assay analysis has been
      proposed, aiming to minimize user interaction and providing reproducible
      measurements. The algorithm comprises two-steps: (a) comet identification via
      Gaussian pre-filtering and morphological operators; (b) comet segmentation via
      fuzzy clustering. The algorithm has been evaluated using comet images from human
      leukocytes treated with a commonly used DNA damaging agent. A comparison of the
      proposed approach with a commercial system has been performed. Results show that
      fuzzy segmentation can increase overall sensitivity, giving benefits in bio
      monitoring studies where weak genotoxic effects are expected.

PMID- 22402890
TI  - The effects of femoral neck cut, cable tension, and muscles forces on the greater
      trochanter fixation.
AB  - Greater trochanter (GT) stabilization techniques following a fracture or an
      osteotomy are still showing high levels of postoperative complications.
      Understanding the effect of femoral neck cut placement, cable tension and muscles
      forces on GT fragment displacements could help surgeons optimize their
      techniques. A 3D finite element model has been developed to evaluate, through a
      statistical experimental design, the impact of the above variables on the GT
      fragment gap and sliding displacements. Muscles forces were simulating typical
      daily activities. Stresses were also investigated. The femoral neck cut placement
      had the most significant effect on the fragment displacement. Lowering it by 5 mm
      increased the gap and sliding fragment displacements by 288 and 128 %,
      respectively. Excessive cable tightening provided no significant reduction in
      fragment displacement. Muscle activities increased the gap and the sliding
      displacements for all muscle configurations. The maximum total displacement of
      0.41 mm was present with a 10 mm femoral neck cut, a cable tension of 178 N, and
      stair climbing. Caution must be used not to over tighten the cables as the
      potential damage caused by the increased stress is more significant than any
      reduction in fragment displacement. Furthermore, preservation of the contact area
      is important for GT stabilization.

PMID- 22402892
TI  - Cerebrospinal fluid levels of Abeta42 relationship with cholinergic cortical
      activity in Alzheimer's disease patients.
AB  - The dysfunction of cholinergic neurons is a typical hallmark in Alzheimer's
      disease (AD). In animal models of AD, fragments of amyloid beta protein (Abeta)
      and Tau protein are thought to interfere with central cholinergic transmission,
      specifically with synthesis and release of acetylcholine. Thus, we aimed to
      investigate whether the cerebrospinal fluid (CSF) levels of Abeta42 and Tau
      proteins in AD patients could influence physiological central cholinergic
      activity. In AD patients (n = 19), central cholinergic function was evaluated in
      vivo by using short afferent latency inhibition (SLAI), and compared to age
      matched healthy controls. In the same AD patients, CSF samples were collected
      through lumbar puncture to obtain individual levels of Abeta42, total Tau (t-Tau)
      and phosphorylated Tau (p-Tau) (Thr181). SLAI was decreased in AD patients in
      comparison to age-matched healthy controls. We found that in patients there was a
      negative correlation between the individual amount of cholinergic activity
      assessed by SLAI and the CSF levels of Abeta42. On the other hand, there was a
      positive correlation between the levels of SLAI and CSF p-Tau. No correlation was
      found when SLAI was analysed together with t-Tau. These results demonstrate that
      mechanisms of cortical cholinergic activity are altered in patients bearing a
      pathological CSF hallmark of AD, suggesting that these peptides may have some
      influence on the cholinergic dysfunction in AD. We suggest that coupling of CSF
      biomarkers with neurophysiological parameters of central cholinergic function
      could be important to better detect ongoing mechanisms of neural degeneration in
      vivo.

PMID- 22402893
TI  - Knockdown of microplitis mediator odorant receptor involved in the sensitive
      detection of two chemicals.
AB  - Odorant receptors are thought to play critical roles in the perception of
      chemosensory stimuli by insects. The primary method to address the functions of
      odorant receptors in insects is to use in vitro binding assays between the
      receptors and potential chemical stimuli. We injected MmedOrco dsRNA into the
      abdominal cavity of a braconid wasp, Microplitis mediator, and assayed for
      expression of this gene 72 h after treatment (RNAi). Quantitative real-time PCR
      demonstrated that the level of mRNA expression in MmedOrco dsRNA-treated M.
      mediator was significantly reduced (>90%) when compared with water-treated
      controls. Furthermore, electroantennogram (EAG) responses of M. mediator to two
      chemical attractants, nonanal and farnesene, were also reduced significantly
      (~70%) in RNAi-treated M. mediator when compared to controls. RNAi-treated M.
      mediator also responded by walking/flying at a lower rate to both chemicals when
      compared with controls in a Y-tube olfactometer bioassay, which provides direct
      evidence that MmedOrco plays an important role in perception of nonanal and
      farnesene in M. mediator.

PMID- 22402895
TI  - Military hierarchy, job stress and mental health in peacetime.
AB  - BACKGROUND: Most studies of mental health in the armed forces focus primarily on
      post-traumatic stress disorders among military personnel in combat situations.
      AIMS: To evaluate the prevalence of common mental disorders (CMD) and job stress,
      and the association between the two, among military personnel in peacetime.
      Additionally, it sought to identify occupational subgroups with higher
      prevalences of CMD. METHODS: The study participants were 506 military personnel
      from a Brazilian army directorate in Rio de Janeiro City. CMD were evaluated
      using the 12-item version General Health Questionnaire. Job characteristics were
      measured using the effort-reward imbalance (ERI) model and by categories of
      military rank. Prevalence ratios (PRs) were estimated by Poisson regression to
      obtain robust (95%) confidence intervals (CIs). RESULTS: The prevalence of CMD
      was 33% (95% CI 29-37). After adjusting for age, education, income, lifestyle and
      other occupational characteristics, ERI was associated with CMD (PR = 2.03; 95%
      CI 1.3-3.1). Overcommitment proved to be an important component of job stress.
      Independently of socio-economic, demographic, lifestyle and job stress variables,
      the rank of lieutenant associated strongly with CMD (PR = 2.02; 95% CI 1.2-4
      0.1). CONCLUSIONS: This study found that job stress among armed forces personnel
      is associated with CMD. In addition, the specific occupational characteristics of
      the military environment can lead to a higher prevalence of CMD among those
      holding the rank of lieutenant.

PMID- 22402896
TI  - Vision, retinal thickness, and foveal avascular zone size after intravitreal
      bevacizumab for diabetic macular edema.
AB  - INTRODUCTION: To investigate three monthly intravitreal bevacizumab (IVB)
      injections effects in chronic diabetic macular edema (DME). METHODS: A
      prospective, noncomparative study in which inclusion criteria were; DME with
      central macular thickness (CMT) of at least 250 MUm, and no treatment for
      diabetic retinopathy (DR) within 4 months before the first injection. All eyes
      received three monthly 1.25 mg IVB injections. CMT by optical coherence
      tomography, visual acuity (VA), foveal avascular zone (FAZ) greatest linear
      dimension (GLD), and area of FAZ by fundus fluorescein angiography were
      documented initially and 1 month after last injection. Outcomes (P<0.05 were
      significant) and correlations (r values) were analyzed. RESULTS: A total of 29
      eyes of 29 patients (group 1, 19 female, 10 male), aged 60.7+/-6.6 years were
      analyzed. The patients were split into two groups; group 2 included 15 mild-to
      moderate nonproliferative DR, and group 3 included 14 more-severe DR. VA gain was
      significant in all groups (P<0.05). Mean CMT decrease was approximately 46, 36,
      and 55 MUm in groups 1, 2, and 3, respectively (P<0.05 only in group 1). A 0.045
      mm2 increase in FAZ area was obtained in group 1 (P<0.05). In group 2, an
      increase in GLD and area of FAZ was 0.048 mm and 0.058 mm2, respectively
      (P<0.05), whereas in group 3, FAZ enlargement was nonsignificant. VA and CMT were
      significantly correlated (r values=0.5-0.6), except for the final VA-final CMT in
      group 2. FAZ dimensions and other parameters (VA and CMT) were noncorrelated.
      CONCLUSION: According to the authors' short-term results, three monthly IVB
      injections can be used for chronic DME regardless of VA, CMT, or FAZ dimensions,
      despite the FAZ enlargement encountered, especially in cases with milder DR.

PMID- 22402897
TI  - [A survey of reflux-associated illnesses in the head and neck area].

PMID- 22402898
TI  - [The possibilities of reflux disease diagnosis by the ear, nose and throat
      specialist].
AB  - Reflux disease has gained in importance over the last decade since we know that
      many of the symptoms and diseases of the upper aerodigestive tract might be
      associated with reflux. However, a distinction needs to be made between
      extraesophageal reflux (EER) and gastroesophageal reflux disease (GERD). There
      are several techniques available for the diagnosis of EER. Furthermore, there are
      various pH monitoring devices to determine acid contamination of the larynx and
      the pharynx. In addition, flexible transnasal esophagoscopy is a practicable
      technique for the rapid examination of reflux, its cause as well as the diagnosis
      of reflux-induced mucosal changes in the esophagus. The present article describes
      the instruments used for the diagnosis of reflux against the background of our
      own experience and the international literature.

PMID- 22402899
TI  - [Diagnosis and therapy of atypical reflux symptoms when PPI therapy fails].
AB  - Gastroesophageal reflux disease (GERD) is a frequent chronic disorder occurring
      in two forms: on the one hand, typical symptoms such as heartburn and acid
      regurgitation are seen, while on the other hand atypical (extraesophageal)
      symptoms such as chronic cough, hoarseness, recurrent sinusitis, globus
      sensations in the throat, a burning feeling on the tongue, dental erosions and
      the constant need to clear the throat can be associated with gastroesophageal
      reflux. The standard therapeutic medical procedure comprises the administration
      of acid-suppressive agents, proton pump inhibitors (PPI). However, this therapy
      has proved to be ineffective in a number of patients, especially in atypical
      GERD. Only after reliable identification of the GERD patient by using valid
      diagnostic tools medical or interventional therapeutic options can be applied
      individually. In the absence of atypical GERD symptoms, the diagnosis of GERD
      becomes very unlikely and other causes of the symptoms need to be taken into
      consideration.

PMID- 22402900
TI  - [Laryngopharyngeal reflux and larynx-related symptoms].
AB  - BACKGROUND: Chronic hoarseness, globus sensation or mucous obstruction are among
      a wide range of symptoms possibly related to laryngopharyngeal reflux (LPR).
      METHOD AND RESULTS: A selective literature research was carried out using PubMed,
      in which original articles and reviews in German and English were included.
      Altogether, 2541 articles were found. Despite the large number of publications,
      there are still open questions regarding aspects of LPR. DISCUSSION: It can be
      assumed that refluxate reaching the larynx can damage it. Due to the fact that
      the symptoms possibly related to LPR can, however, be linked to other causes, a
      careful consideration of the patient's medical history is of the utmost
      importance, followed by mandatory laryngoscopy. Diagnostic procedures, such as
      the trial administration of proton pump inhibitors (PPI) or long-term pH
      measurement should be used selectively. Depending on the individual symptoms,
      breathing or voice therapy and/or PPI therapy might be useful. Lifestyle changes
      including dietary measures should also be contemplated.

PMID- 22402901
TI  - [Gastroesophageal reflux diseases in childhood. Diagnosis and therapy].
AB  - Gastroesophageal reflux diseases represent a diagnostic challenge, not least
      since no single diagnostic procedure has been able to establish a causal link
      between pathological reflux and chronic upper and lower airway diseases. By
      combining a variety of procedures which point to a link (multi-channel pH
      measurement, impedance measurement of the esophagus, video panendoscopy,
      bronchoalveolar lavage, and quantification of lipid-laden alveolar macrophages)
      and careful differential and exclusion diagnoses, reflux-related diseases can be
      diagnosed with sufficient precision. In addition to initially successful PPI
      therapy, surgical intervention (hemifundoplication) is the method of choice in
      children.

PMID- 22402902
TI  - [Pediatric OSAS and otitis media with effusion].
AB  - BACKGROUND: Adenotonsillar hyperplasia is considered as a possible cause for two
      frequent ENT disorders in children: pediatric obstructive sleep apnea syndrome
      (OSAS) and otitis media with effusion (OME). The present study analyzes whether a
      link between pediatric OSAS and OME can also be presumed. METHODS:
      Polysomnographic data of 186 children with suspected OSAS were correlated to
      middle ear ventilation assessed by tympanometry. Tympanograms were classified
      according to Jerger. RESULTS: In a Kruskal Wallis test, children with an apnea
      hypopnea index  < 1 (exclusion of OSA by tight criteria), 1-5 or  > 5
      (definitively pathological value) did not statistically significantly differ in
      the prevalence of normally ventilated ears and OME. Accordingly, the Mann-Whitney
      U test showed that children with normally ventilated ears did not have a
      statistically different apnea-hypopnea, apnea, hypopnea or snoring index or
      varying minimal oxygen saturation to children suffering from OME. CONCLUSIONS: In
      the present study, no link was detected between pediatric OSAS and OME.

PMID- 22402903
TI  - [Identifying language and communication disorders as part of the medical
      curriculum].
AB  - BACKGROUND: Like hearing loss, language and speech disorders can also lead to
      impaired communication. Speech and language disorders can occur at any age, for
      example as a specific language impairment, stuttering, dysarthria, and aphasia.
      Hence, irrespective of their speciality, there is a high probability that
      physicians will at some point encounter communication-impaired patients, be
      required to classify their disorder and refer them for appropriate therapy.
      METHODS: A new module entitled 'communication disorders' consisting of two
      teaching units was integrated in the practical course 'ENT--phoniatrics-
      pedaudiology' for undergraduate clinical students in 2008. The learning objective
      of the first unit was to identify and classify communication disorders, presented
      using sound and video data, by means of simple criteria. The module was evaluated
      on the basis of questionnaires completed by 164 students. RESULTS: On a scale of
      1-7, the evaluation showed overall positive results with 6.54 (highest score) for
      professional competence and 5.32 (lowest score) for discussion. The overall score
      was 12.28 out of a possible maximum of 15 points. CONCLUSION: The ability to
      identify communication impairments is an important medical skill. Since
      communication disorders are common diseases we suggest that this skill be
      incorporated in the medical curriculum. Thus we have introduced a module for
      communication disorders; its evaluation by students shows a high level of
      satisfaction in each category. After developing specific diagnostic indicators
      students were able to independently describe and identify communication
      disorders.

PMID- 22402905
TI  - [Receptor function of the semicircular canals. Part 2: pathophysiology, diseases,
      clinical findings and treatment aspects].
AB  - Perturbation of semicircular canal function may result in a pathological angular
      vestibulo-ocular reflex (aVOR). The resulting impairment in gaze stabilization is
      perceived as "vertigo" or "dizziness" and may occur following receptor function
      impairment of all three semicircular canals. The head impulse test reveals hidden
      (covert-catchup) or visible (overt-catchup) saccades in disturbances of
      semicircular function. Most peripheral vestibular disorders can be treated
      conservatively. There are surgical treatment options for some diseases, such as
      intractable benign paroxysmal positional vertigo and superior semicircular canal
      dehiscence. Vestibular training promotes central reorganization of the VOR.
      Impaired semicircular receptor function, in particular bilateral vestibulopathy,
      may affect spatial orientation and cognitive processes. Balance prostheses could
      serve as a replacement for receptors in the future.

PMID- 22402906
TI  - [Phonological loop and low level phonological processing in preschool children].
AB  - BACKGROUND: Phoneme discrimination tests based on presenting minimal pairs (MP)
      are frequently used to assess auditory processing. However, test results may be
      influenced by other factors beside correct acoustic representation. Here we
      studied if working memory capacity (WMC) correlates with reproducing sets of
      minimal pairs. METHODS: Participants were 161 preschool children whereby WMC was
      evaluated by memory span for digits and MPs were either real words or non-words
      (logatoms). Both real word MPs and logatom MPs were presented in doublets or
      triplets. Children were asked to repeat what they had heard. Correlation analysis
      was performed using Spearman rank correlation. RESULTS: All four test item blocks
      showed a significant positive correlation to WMC (group values). Data from
      individuals indicated that some children with poor WMC performed sufficiently on
      MP discrimination and vice versa. DISCUSSION: Besides confirming the phonological
      similarity effect our data indicate a significant interdependence between
      different processes and phonological representations (according to the Logogen
      model). This must be taken into account when using MP tests for evaluating
      "auditory processing" in the clinical routine. However, poor WMC is neither
      necessary nor obligatory for poor phoneme discrimination.

PMID- 22402907
TI  - Intact interferon signaling in peripheral blood leukocytes of high-grade
      osteosarcoma patients.
AB  - High-grade osteosarcoma has a poor prognosis with an overall survival rate of
      about 60 percent. The recently closed European and American Osteosarcoma Study
      Group (EURAMOS)-1 trial investigates the efficacy of adjuvant chemotherapy with
      or without interferon-alpha. It is however unknown whether the interferon
      signaling pathways in immune cells of osteosarcoma patients are functional. We
      studied the molecular and functional effects of interferon treatment on
      peripheral blood lymphocytes and monocytes of osteosarcoma patients, both in vivo
      and ex vivo. In contrast to other tumor types, in osteosarcoma, interferon
      signaling as determined by the phosphorylation of signal transducer and activator
      of transcription (STAT)1 at residue 701 was intact in immune cell subsets of 33
      osteosarcoma patients as compared to 19 healthy controls. Also, cytolytic
      activity of interferon-alpha stimulated natural killer cells against allogeneic
      (n = 7 patients) and autologous target cells (n = 3 patients) was not impaired.
      Longitudinal monitoring of three osteosarcoma patients on interferon-alpha
      monotherapy revealed a relative increase in the CD16-positive subpopulation of
      monocytes during treatment. Since interferon signaling is intact in immune cells
      of osteosarcoma patients, there is a potential for indirect immunological effects
      of interferon-alpha treatment in osteosarcoma.

PMID- 22402909
TI  - Comparison of overlapping (OP) and adjacent thumb positions (AP) for cardiac
      compressions using the encircling method in infants.
AB  - OBJECTIVES: The aim of this manikin study was to compare the efficiency between
      overlapping (OP) and adjacent thumb positions (AP) for cardiac compressions using
      the encircling method in infants. METHODS: The study conducted from December 2010
      to August 2011 involved 48 volunteers who were students in the emergency medical
      technician course. The authors let volunteers practice OP and AP as a crossover
      design. The authors monitored the simulated mean arterial pressure (MAP)
      generated during a 5-min chest compression. The fatigue level of the volunteers
      after the chest compression was evaluated with the Likert scale. RESULTS: There
      were no significant differences in MAP between the dominant hand and the non
      dominant hand as the lower thumb of OP. Significant differences were observed in
      simulated systolic blood pressure, MAP and simulated pulse pressure between OP
      and AP at 1, 2, 3, 4 and 5 min. There were no significant differences among the
      changes in heart rate, respiratory rate and end-tidal CO(2) during a 5-min chest
      compression by OP and AP. The Likert scale scores (1 no fatigue to 5 = extreme
      fatigue) during the 5-min chest compressions were higher in AP than in OP at 2, 3
      and 5 min. CONCLUSION: Higher intrathoracic pressures were achieved by OP in this
      study. However, further studies are needed to validate these effects of
      overlapping thumbs technique in infant cardiopulmonary resuscitation, not
      manikin.

PMID- 22402910
TI  - Vitreoretinal surgery in the management of war-related open-globe injuries.
AB  - BACKGROUND: Ranking among the most severe combat damages, war-related open-globe
      injuries (WROGIs) are not uniform, so the treatment approaches are sometimes
      unclear. The essential issue is to define exact indications for time- and
      resource-intensive vitreoretinal surgery (VRS), known to be an effective
      procedure for severe posterior segment injuries. We studied WROGI structure, and
      summarized the experience of specialized ophthalmologic care (SOC) management
      during local armed conflicts (LACs). METHODS: This was a retrospective
      multicenter study that included case series of 203 wounded subjects (314 eyes)
      with WROGIs sustained during LACs treated in the hospitals of first, second and
      third echelons of SOC. Ocular trauma was classified according to the
      International Society of Ocular Trauma (ISOT) classification, and only open-globe
      injuries (OGI) made up two groups of study: injured eyes that underwent VRS, n =
      135, and those eyes on which VRS was not performed, n = 119. Two subgroups
      according to stages of VRS were also included. We reviewed the demographic
      characteristics, the time between injury and surgery, the number of stages in
      which surgery was performed, and initial visual acuity (IVA) at arrival and final
      visual acuity (FVA), 12 months after surgery. RESULTS: WROGI constituted 65.1 %
      of all eyes injured. The visual outcomes after VRS were favorable in ruptures of
      the eye, penetrating WROGIs, intraocular foreign body (IOFB) WROGIs, perforating
      WROGIs (types A, B, C, D) of grades 1-4. Those WROGIs of grade 5 had poor visual
      outcomes irrespective of the surgeries. In 19.1% of all cases wherein either the
      eye wall or eye content were extensively damaged (included types A, C, D, E of
      grade 5), all attempts to save the eye through reconstructive surgery were
      unsuccessful and led to enucleation (evisceration). CONCLUSIONS: Medical service
      management in LACs demands to define groups of priority for VRS between the
      wounded with WROGI during triage at the first echelon of SOC. Multistage VRS
      determines unfavorable outcomes of the WROGI. Treatment should be determined by
      diagnosis, and there is a need to introduce a new category into the OGI
      classification--eye destruction, because only this damage determines the choice
      of enucleation/evisceration of the eye.

PMID- 22402911
TI  - Studies on HOXB4 expression during differentiation of human cytomegalovirus
      infected hematopoietic stem cells into lymphocyte and erythrocyte progenitor
      cells.
AB  - We investigated the role of homeobox B4 (HOXB4) mRNA/protein expression induced
      by human cytomegalovirus (HCMV) and/or all-trans retinoic acid (ATRA) in
      proliferation and committed differentiation of human cord blood hematopoietic
      stem cells (HSCs) into colony-forming-units of T-lymphocyte (CFU-TL) and
      erythroid (CFU-E) progenitors in vitro. Twelve cord blood samples were collected
      from the fetal placenta umbilical vein and cultured in vitro. The proliferation
      and differentiation of cord blood HSCs into CFU-TL and CFU-E were continuously
      disrupted with HCMV-AD169 and/or 6 * 10(-8) mol/l of ATRA. HOXB4 mRNA/protein
      expression in CFU-TL and CFU-E was detected in control, ATRA, HCMV and ATRA +
      HCMV groups on days 3, 7, and 12 of culture by fluorescent qRT-PCR/western blot.
      We found that HOXB4 mRNA/protein expression was detectable on day 3, increased on
      day 7 and was highest on day 12. HOXB4 mRNA/protein expression in HCMV group was
      downregulated compared with control group (P < 0.05). However, the levels were
      significantly upregulated in HCMV + ATRA group compared with HCMV group (P <
      0.05). We concluded that the abnormal HOXB4 mRNA/protein expression induced by
      HCMV could play a role in hematopoietic damage. ATRA, at the concentration used,
      significantly up-regulated HOXB4 mRNA/protein expression in normal lymphocyte and
      erythrocyte progenitor cells as well as in HCMV-infected cells.

PMID- 22402912
TI  - Improvement of central visual function following steroid pulse therapy in acute
      zonal occult outer retinopathy.
AB  - The purpose of this study was to report a patient with acute zonal occult outer
      retinopathy (AZOOR) unilaterally, who received steroid pulse therapy. A 42-year
      old woman presented with photopsias and severe vision loss in her left eye.
      Visual acuity was 0.04, and Humphrey visual field testing showed overall
      depression with a mean deviation (MD) value of -25.78 dB in the left eye. Fundus
      and angiographic examinations found no specific abnormal findings, leading to a
      diagnosis of AZOOR. Optical coherence tomography showed attenuation of the
      photoreceptor inner segment/outer segment junction (IS/OS) line. Focal macular
      electroretinography (fmERG) demonstrated that there were non-detectable responses
      at 5 degrees , 10 degrees  and 15 degrees  (in diameter). Following steroid pulse
      therapy, her visual acuity was 1.0, her MD value improved to -16.08 dB, and there
      were both partial recovery of the IS/OS line and apparent improvements of fmERG
      responses (at 10 degrees  and 15 degrees ). The present findings suggest that
      steroid pulse therapy might potentially be an effective treatment in some AZOOR
      patients.

PMID- 22402913
TI  - The effect of heart rate variability biofeedback on performance psychology of
      basketball players.
AB  - Coping with pressure and anxiety is an ineluctable demand of sports performance.
      Heart rate variability (HRV) Biofeedback (BFB) shall be used as a tool for self
      regulating physiological responses resulting in improved psycho physiological
      interactions. For further analysis, the present study has been designed to
      examine the relationship between anxiety and performance and also effectiveness
      of biofeedback protocol to create stress-eliciting situation in basketball
      players. Thirty basketball players of university level and above (both male and
      female) aged 18-28 years, who scored a minimum of 20 in state trait anxiety
      inventory, were randomly divided into three equal groups- Experimental
      (Biofeedback) group, Placebo group and Control (No Treatment) group. The BFB
      group received HRV BFB training for 10 consecutive days for 20 min that included
      breathing at individual's resonant frequency through a pacing stimulus; Placebo
      group was shown motivational video clips for 10 consecutive days for 10 min,
      whereas No Treatment Control group was not given any intervention. Two way
      repeated measure ANOVA was applied to analyze the differences within and between
      the groups. Anxiety, coping self-efficacy, heart rate variability, respiration
      rate, and performance (dribbling, passing and shooting) at session 1, 10 and 1
      month follow up were statistically significant in each group along with
      interaction of group and time (p < 0.001). Also, all the measures showed
      statistically significant inter group difference (p < 0.05). The findings are
      harmonious with existing data on HRV BFB as a strategy for dealing with anxiety.
      The Placebo group showed improvement in self efficacy and performance post
      training. The Control group showed no change in any variable except performance.
      The results of the study support the idea that HRV BFB lowers the anxiety and
      thus there seems to be a potential association between HRV BFB and performance
      optimization.

PMID- 22402914
TI  - Prevalence and genetic characterization of respiratory syncytial virus (RSV) in
      hospitalized children in Korea.
AB  - Human respiratory syncytial virus (HRSV) is the most common respiratory pathogen
      among infants and young children. To investigate the prevalence and genetic
      characteristics of HRSVs circulating in South Korea, we analyzed medical records
      of patients and performed molecular analysis of the G-protein gene of viruses
      detected from nasopharyngeal aspirates (NPA) of admitted patients at the
      Pediatrics Department of Chungbuk National University Hospital from April 2008 to
      April 2010. Epidemiological data revealed that the prevalence of HRSV infection
      was high during both winter seasons (October 2008 to February 2009 and November
      2009 to February 2010). Of the 297 positive NPA specimens from infants or
      children tested, 67% were identified as HRSV-A while 33% were HRSV-B. The HRSV
      subgroup B was the most dominant in December 2008, but its dominance was
      dramatically replaced by HRSV subgroup A strains by February 2009. Phylogenetic
      analysis of the G protein sequences of HRSVs revealed novel genotypes within the
      HRSV-A (genotype CB-A) and B (genotypes BA11 and CB-B) subgroups in South Korea
      in addition to other strains identified in other countries. Molecular analysis
      also revealed genetic variability at the C-terminal end of the G proteins of the
      two HRSV subgroups, suggesting selection pressure in this region, which may
      potentially impact immune recognition. This is the first report of these HRSV
      variants in South Korea, indicating active genetic evolution of HRSV strains.
      Therefore, this study provides information on the molecular epidemiology of
      current HRSVs in the country and presents data for comparative analysis with
      other HRSV strains circulating worldwide.

PMID- 22402915
TI  - The usefulness of combined measurements of squamous cell carcinoma antigens 1 and
      2 in diagnosing atopic dermatitis.
AB  - BACKGROUND: The squamous cell carcinoma antigen (SCCA) is widely used as a
      serological biomarker for various cancers. There are two known SCCA molecules,
      SCCA1 and SCCA2. We previously found that interleukin-4 or interleukin-13, two
      related Th2-type cytokines that play an important role in allergic diseases,
      induce expression of SCCA1 and SCCA2. In this study, we examined whether combined
      measurements of SCCA1 and SCCA2 are useful for diagnosing atopic dermatitis (AD).
      METHODS: We established new enzyme-linked immunosorbent assays (ELISAs) to
      specifically detect SCCA1 or SCCA2. We applied serum samples from AD patients
      with food allergies and from cervical cancer patients to these ELISAs. We
      performed receiver operating characteristic analyses to diagnose AD and to
      distinguish AD from cervical cancer. RESULTS: Serum concentrations of both SCCA1
      and SCCA2 were elevated in AD patients. The serum concentrations of SCCA1 and
      SCCA2 positively correlated with the clinical severity of AD, showing high
      specificity (0.86-0.88) and sensitivity (0.86) against control donors. The serum
      concentrations of SCCA1 and SCCA2 were elevated in cervical cancer patients;
      however, the SCCA2/SCCA1 ratios clearly distinguished AD patients from cervical
      cancer patients with high specificity (0.87) and sensitivity (0.87). Expression
      of SCCA2 was predominant in AD patients, whereas cervical cancer patients showed
      a predominance of SCCA1. CONCLUSIONS: Combined measurements of SCCA1 and SCCA2
      are very useful in estimating the severity of allergic diseases, making it
      possible to distinguish allergic diseases from cancers.

PMID- 22402917
TI  - Amyloidosis.
AB  - The term amyloid describes the deposition in the extracellular space of certain
      proteins in a highly characteristic, insoluble fibrillar form. Amyloidosis
      describes the various clinical syndromes that occur as a result of damage by
      amyloid deposits in tissues and organs throughout the body. The clinical
      significance of amyloid varies enormously, ranging from incidental asymptomatic
      deposits to localized disease through to rapidly fatal systemic forms that can
      affect multiple vital organs. Currently available therapy is focused on reducing
      the supply of the respective amyloid fibril precursor protein and supportive
      medical care, which together have greatly improved survival. Chemotherapy and
      anti-inflammatory treatment for the disorders that underlie AL and AA amyloidosis
      are guided by serial measurements of the respective circulating amyloid precursor
      proteins, i.e. serial serum free light chains in AL and serum amyloid A protein
      in AA type. Quality of life and prognosis of some forms of hereditary systemic
      amyloidosis can be improved by liver and other organ transplants. Various new
      therapies, ranging from silencing RNA, protein stabilizers to monoclonal
      antibodies, aimed at inhibiting fibril precursor supply, fibril formation or the
      persistence of amyloid deposits, are in development; some are already in clinical
      phase.

PMID- 22402916
TI  - Recommendations for standardized reporting of protein electrophoresis in
      Australia and New Zealand.
AB  - BACKGROUND: Although protein electrophoresis of serum (SPEP) and urine (UPEP)
      specimens is a well-established laboratory technique, the reporting of results
      using this important method varies considerably between laboratories. The
      Australasian Association of Clinical Biochemists recognized a need to adopt a
      standardized approach to reporting SPEP and UPEP by clinical laboratories.
      METHODS: A Working Party considered available data including published literature
      and clinical studies, together with expert opinion in order to establish optimal
      reporting practices. A position paper was produced, which was subsequently
      revised through a consensus process involving scientists and pathologists with
      expertise in the field throughout Australia and New Zealand. RESULTS:
      Recommendations for standardized reporting of protein electrophoresis have been
      produced. These cover analytical requirements: detection systems; serum protein
      and albumin quantification; fractionation into alpha-1, alpha-2, beta and gamma
      fractions; paraprotein quantification; urine Bence Jones protein quantification;
      paraprotein characterization; and laboratory performance, expertise and staffing.
      The recommendations also include general interpretive commenting and commenting
      for specimens with paraproteins and small bands together with illustrative
      examples of reports. CONCLUSIONS: Recommendations are provided for standardized
      reporting of protein electrophoresis in Australia and New Zealand. It is expected
      that such standardized reporting formats will reduce both variation between
      laboratories and the risk of misinterpretation of results.

PMID- 22402918
TI  - Community SES, perceived environment, and physical activity during home-based
      cardiac rehabilitation: is there a need to consider the urban vs. rural
      distinction?
AB  - Physical activity (MVPA) levels during home-based cardiac rehabilitation (CR)
      remain problematic. Consequently, the present study examined the association
      between MVPA and urban vs. rural residential status and the perceived environment
      in patients attending home-based CR. A total of 280 patients completed a
      questionnaire assessing demographic, clinical, MVPA, and perceived environmental
      variables measured at baseline and 3 months later. Patient addresses were
      geocoded and linked to the 2006 Canadian census to establish the urban/rural
      distinction. Results showed that urban and rural patients had similar baseline
      MVPA and improvements in MVPA by 3 months. Several perceived environmental
      variables were significantly related to MVPA throughout home-based CR that were
      common and urban/rural-specific. Therefore, although there does not appear to be
      an urban vs. rural advantage in MVPA levels during home-based CR, there does
      appear to be environmental/MVPA-specific relationships specific to urban and
      rural patients that may warrant attention.

PMID- 22402919
TI  - Partial stapled hemorrhoidopexy versus circular stapled hemorrhoidopexy for grade
      III-IV prolapsing hemorrhoids: a two-year prospective controlled study.
AB  - BACKGROUND: Circular stapled hemorrhoidopexy (CSH) is an effective technique for
      treating prolapsing hemorrhoids; but urgency and anal stenosis are common
      postoperative complications. The aim of this study was to assess the efficacy and
      postoperative outcomes of partial stapled hemorrhoidopexy (PSH), compared with
      CSH. METHODS: Seventy-two consecutive patients with grade III and IV hemorrhoids
      who met the inclusion/exclusion criteria were divided in a non-randomized manner
      to undergo either PSH (n = 34) or CSH (n = 38). Intraoperative and postoperative
      parameters in both groups were collected and compared. RESULTS: The postoperative
      visual analog score for pain at first defecation was significantly lower in the
      PSH group than that in the CSH group (P = 0.001). Fewer patients in the PSH group
      experienced postoperative urgency, compared with those in the CSH group at 12 h,
      1 day, and 7 days after surgery (P = 0.025, P = 0.019, and P = 0.043,
      respectively). Gas incontinence occurred in 3 patients (7.9%) in the CSH group,
      but in none of patients in the PSH group (P = 0.242). Postoperative anal stenosis
      developed in one patient (2.6%) in the CSH group, but in none of the patients in
      the PSH group (P = 1.0). The 2-year recurrence rate was 2.9 and 5.3%,
      respectively, in the PSH and CSH groups (P = 1.0). CONCLUSIONS: The 2-year
      recurrence rate is similar in patients with grade III-IV hemorrhoids treated with
      PSH or CSH. However, PSH is associated with less postoperative pain, fewer
      episodes of urgency, and no anal incontinence or anal stenosis.

PMID- 22402920
TI  - Insulin-like growth factor I and anthropometric parameters in a Danish
      population.
AB  - During the last decade several studies indicated that low insulin-like growth
      factor (IGF) I levels are related to higher risk of cardiovascular disease and
      mortality. Obesity represents one further main cardiovascular risk factor which
      might also be related to IGF-I. The objective of the present study was to analyse
      the associations between anthropometric measures and IGF-I levels in a population
      based sample. From the Danish cross-sectional Health2006 study 3,328 subjects
      (1,835 women; 1,493 men) aged 19-72 years were included in the analyses. Serum
      IGF-I levels were determined by an immunoassay. Body height, weight as well as
      waist and hip circumferences were measured. Body-mass-index, waist-to-hip ratio
      and waist-to-height ratio were calculated. Circulating IGF-I levels were
      inversely associated with all anthropometric markers as evaluated by linear
      regression adjusting for age, alcohol consumption, smoking and physical activity.
      Our large cross-sectional study suggests that IGF-I may serve as the link between
      obesity and mortality although any causal relation cannot be inferred and
      longitudinal analyses are needed to clarify the causal relation.

PMID- 22402921
TI  - Apocarotenoids in the sexual interaction of Phycomyces blakesleeanus.
AB  - A simple genetic test allowed us to carry out the first systematic study of the
      apocarotenoids in the Mucorales. We have identified 13 apocarotenoids in the
      culture media of the fungus Phycomyces blakesleeanus (Mucoromycota, Mucorales).
      Three of these compounds were novel apocarotenoids: (2S,8R,E)-8,14
      epoxycyclofarnesa-4,6,9-triene-2,11-diol (6), (2S,6E,8E)-cyclofarnesa-4,6,8
      triene-2,10,11-triol (7), and its 6Z isomer (8). Four of the remaining compounds
      have been reported previously from this fungus and six from other Mucorales. All
      of them belong to three families, the 18-carbon trisporoids, the 15-carbon
      cyclofarnesoids, and the 7-carbon methylhexanoids, derived from the three
      fragments that result when beta-carotene is cleaved at its 11',12' and 12,13
      double bonds. The apocarotenoids were more varied and more abundant in mated
      cultures of strains of opposite sex than in single cultures. The presence of
      acetate in the medium blocked the production of many apocarotenoids while having
      little effect on the concentrations of the remaining ones.

PMID- 22402923
TI  - Feasibility of TWA testing - reply.

PMID- 22402924
TI  - The road to cardioversion paved by allied professionals.

PMID- 22402925
TI  - Perception of pregnancy related health issues among Arab women living in the
      United States.
AB  - Ethnic minorities living in the US have lower utilization and access to prenatal
      care, resulting in an increased risk of adverse pregnancy outcomes. The present
      study examines utilization of prenatal care, perceived pregnancy related health,
      and perceived risk of adverse pregnancy outcomes among Arab women living in the
      USA cross-sectional study was conducted, consisting of a convenience sample of
      170 Arab women. A structured questionnaire was administered by a face-to-face or
      telephone interview. Multivariable logistic regression was used to calculate
      adjusted Odds Ratios and 95% Confidence Intervals, controlling for potential
      confounders. All study participants had received prenatal care during their most
      recent pregnancy, and 90% had their first prenatal care visit before the 12th
      gestational week. The Arab women who were older (P = 0.02), those with 12 years
      of education or less (P = 0.002), and those who had lived in the US more than
      five years (P = 0.0002) were more likely to report four or more pregnancies. In
      addition, more than one-third of the women reported having experienced a
      miscarriage (35.4%), which was significantly associated with gravida status (P <
      0.001). An association between perceived susceptibility for spontaneous abortion
      and stillbirth was also demonstrated (P < 0.0001). Although Arab women reported
      good coverage of prenatal care, they perceived themselves as susceptible for
      several pregnancy complications and adverse pregnancy outcomes. Clinical
      guidelines for prenatal care to Arab women should therefore focus on their high
      parity and likelihood of miscarriages, in an attempt to reduce their risk of
      adverse pregnancy outcomes.

PMID- 22402926
TI  - Effect of tribal language use on colorectal cancer screening among American
      Indians.
AB  - American Indians have one of the lowest colorectal cancer (CRC) screening rates
      for any racial/ethnic group in the U.S., yet reasons for their low screening
      participation are poorly understood. We examine whether tribal language use is
      associated with knowledge and use of CRC screening in a community-based sample of
      American Indians. Using logistic regression to estimate the association between
      tribal language use and CRC test knowledge and receipt we found participants
      speaking primarily English were no more aware of CRC screening tests than those
      speaking primarily a tribal language (OR = 1.16 [0.29, 4.63]). Participants who
      spoke only a tribal language at home (OR = 1.09 [0.30, 4.00]) and those who spoke
      both a tribal language and English (OR = 1.74 [0.62, 4.88]) also showed
      comparable odds of receipt of CRC screening. Study findings failed to support the
      concept that use of a tribal language is a barrier to CRC screening among
      American Indians.

PMID- 22402927
TI  - On the significance of adult play: what does social play tell us about adult
      horse welfare?
AB  - Play remains a mystery and adult play even more so. More typical of young stages
      in healthy individuals, it occurs rarely at adult stages but then more often in
      captive/domestic animals, which can imply spatial, social and/or feeding
      deprivations or restrictions that are challenging to welfare, than in animals
      living in natural conditions. Here, we tested the hypothesis that adult play may
      reflect altered welfare states and chronic stress in horses, in which, as in
      several species, play rarely occurs at adult stages in natural conditions. We
      observed the behaviour (in particular, social play) of riding school horses
      during occasional outings in a paddock and measured several stress indicators
      when these horses were in their individual home boxes. Our results revealed that
      (1) the number of horses and rates of adult play appeared very high compared to
      field report data and (2) most stress indicators measured differed between
      'players' and 'non-players', revealing that most 'playful' animals were suffering
      from more chronic stress than 'non-playful' horses. Frequency of play behaviour
      correlated with a score of chronic stress. This first discovery of a relationship
      between adult play and altered welfare opens new lines of research that certainly
      deserves comparative studies in a variety of species.

PMID- 22402928
TI  - Computational method for quantifying growth patterns at the adaxial leaf surface
      in three dimensions.
AB  - Growth patterns vary in space and time as an organ develops, leading to shape and
      size changes. Quantifying spatiotemporal variations in organ growth throughout
      development is therefore crucial to understand how organ shape is controlled. We
      present a novel method and computational tools to quantify spatial patterns of
      growth from three-dimensional data at the adaxial surface of leaves. Growth
      patterns are first calculated by semiautomatically tracking microscopic
      fluorescent particles applied to the leaf surface. Results from multiple leaf
      samples are then combined to generate mean maps of various growth descriptors,
      including relative growth, directionality, and anisotropy. The method was applied
      to the first rosette leaf of Arabidopsis (Arabidopsis thaliana) and revealed
      clear spatiotemporal patterns, which can be interpreted in terms of gradients in
      concentrations of growth-regulating substances. As surface growth is tracked in
      three dimensions, the method is applicable to young leaves as they first emerge
      and to nonflat leaves. The semiautomated software tools developed allow for a
      high throughput of data, and the algorithms for generating mean maps of growth
      open the way for standardized comparative analyses of growth patterns.

PMID- 22402929
TI  - Effects of corticotropin-releasing factor 1 receptor antagonism on the
      hypothalamic-pituitary-adrenal axis of rodents.
AB  - Corticotropin-releasing factor (CRF) is the major hypothalamic neuropeptide
      responsible for stimulation of the hypothalamic-pituitary-adrenal axis (HPAA),
      resulting in the synthesis and release of glucocorticoids from the adrenal
      cortex. In a recent study, we reported the discovery of the CRF1 receptor
      antagonist, 3-(4-chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6
      dimethyl-imidazo[1,2-b]pyridazine (MTIP), which has efficacy in preclinical
      models of stress-induced alcohol consumption. Because CRF1 is important in HPAA
      activation, we evaluated the effects of MTIP administration on rodent HPAA
      function. Initial studies established the MTIP doses required for brain and
      pituitary CRF1 occupancy and those associated with the inhibition of
      intracerebroventricular CRF on the HPAA in mice. Then, rat basal plasma
      corticosterone (CORT) concentrations were measured hourly by radioimmunoassay for
      24 h after three daily doses of MTIP or vehicle. In these studies, the early
      phase of the nocturnal CORT surge was reduced; however, the area under the CORT
      curve was identical for the 24-h period. In subsequent studies, increases in
      plasma CORT due to direct pharmacological manipulation of the HPAA axis or by
      stressors were evaluated after MTIP treatment in mice. MTIP attenuated CORT
      responses generated by immediate bolus administration of insulin or ethanol;
      however, MTIP did not affect activation of the HPAA by other stressors and
      pharmacological agents. Therefore, MTIP can modulate basal HPAA activity during
      the CORT surge and reduced activation after a select number of stressors but does
      not produce a lasting suppression of basal CORT. The ability of MTIP to modulate
      plasma CORT after hyperinsulinemia may provide a surrogate strategy for a target
      occupancy biomarker.

PMID- 22402930
TI  - The impact of different grazing periods in dry grasslands on the expansive grass
      Arrhenatherum elatius L. and on woody species.
AB  - Dry grasslands are one of the most species rich and endangered types of
      vegetation in Europe. In the Czech Republic, dry grasslands are mainly of
      anthropogenic origin and were formed as a result of grazing after the clear
      cutting of thermophilous oak woods. Gradual changes in the farming landscape
      throughout the 20th century, particularly in the 1960s, resulted in the
      abandonment of the relatively infertile habitats of dry grasslands. After
      abandonment, dry grasslands decline and degrade due to the gradual overgrowth of
      woody species and expansion of perennial tall grasses. In the year 2000, a
      grazing management program was introduced in the protected areas within the
      territory of Prague City to maintain the species diversity of dry grasslands. The
      responses of the expansive grass species, Arrhenatherum elatius L. and multiple
      woody species (especially, Prunus spinosa L.) to differences in grazing periods
      were monitored for over a decade. Grazing in spring through the end of June had
      the greatest impact on the reduction of A. elatius and woody species. Grazing in
      the height of summer through autumn did not reduce the cover of these plants, and
      may support the prosperity of both A. elatius and the woody species due to higher
      levels of nutrients.

PMID- 22402931
TI  - A participatory assessment of ecosystem services and human wellbeing in rural
      Costa Rica using photo-voice.
AB  - Human well-being is intricately connected to ecosystem services. A keystone
      contribution to the ecosystem service literature has been the Millennium
      Ecosystem Assessment, MA, (Ecosystems and human well-being: a framework for
      assessment, Island Press, Washington, DC; 2003, 2005). Much of the work on
      ecosystem services to date has focused on the assessment and classification of
      environmental functions. The need for inclusion of community perspectives in
      ecosystem assessments has been widely recognized in order to better understand
      the distribution of impacts and benefits resulting from natural resource use.
      Communities can offer a direct route to understanding the complex relationships
      between ecosystems and human well-being and how environmental management affects
      their livelihoods. Photovoice has been made popular as a tool for participatory
      needs assessment but it has had limited use in ecosystem assessments to date. The
      purpose of this paper is twofold: (1) to present the results of a community-level
      assessment of environmental services in a watershed dominated by pineapple
      monoculture in Costa Rica; and (2) to evaluate the strengths and the limitations
      of photovoice as a tool for mapping the relationship between ecosystems and
      people. I argue that photovoice is an underutilized methodology that has the
      potential to complement biophysical ecosystem service assessments in the context
      of impoverished and resource-dependent communities, particularly, since assessing
      ecosystem services and acting upon that information requires integrating the
      knowledges of diverse stakeholders, recognizing power imbalances, and grappling
      with the complexity of social-ecological systems. Processes such as photovoice
      have the potential to catalyze community self-organization, which is a critical
      component for empowerment.

PMID- 22402933
TI  - Reproducibility of different methods to measure the endothelial function.
AB  - This study compares the reliability and reproducibility of flow-mediated
      dilatation (FMD) and peripheral arterial tonometry (PAT) to assess endothelial
      function. Eighteen volunteers with coronary heart disease underwent simultaneous
      testing of FMD by means of brachial artery ultrasound scanning and PAT with the
      EndoPAT 2000. The subjects underwent both tests twice with an interval of 30
      minutes and the same protocol was repeated 2 days later. The within-day
      variability was lower for the FMD measurements than for the PAT measurements (10%
      versus 18%; p < 0.05). The between-day variability was similar (11%). A
      significant correlation was found between PAT and FMD (r = 0.57, p < 0.001). The
      typical errors of measurements for FMD were lower than those for PAT. In
      conclusion, in this study, FMD demonstrated the best reliability for the within-
      and between-day and separate day measurements when compared to PAT.

PMID- 22402934
TI  - Alteration in angiogenic and anti-angiogenic forms of vascular endothelial growth
      factor-A in skeletal muscle of patients with intermittent claudication following
      exercise training.
AB  - The aims of this study were twofold: (1) to identify whether peripheral artery
      disease (PAD) patients had increased muscle concentration of angiogenic VEGF-A,
      anti-angiogenic VEGF165b or VEGF receptor 1 (VEGF-R1) when compared with control
      subjects, and (2) to evaluate whether exercise training in PAD patients was
      associated with changes in muscle concentration of VEGF-A, VEGF165b or VEGF-R1.
      At baseline, 22 PAD and 30 control subjects underwent gastrocnemius muscle
      biopsy. Twelve PAD patients were treated with supervised exercise training (SET)
      and underwent muscle biopsy after 3 weeks and 12 weeks of training and had
      sufficient tissue to measure VEGF-A, VEGF165b and VEGF-R1 concentrations in
      skeletal muscle lysates by ELISA. Muscle concentrations of VEGF-A and VEGF165b
      were similar in PAD patients versus controls at baseline. At both time points
      after the start of SET, VEGF-A levels decreased and there was a trend towards
      increased VEGF165b concentrations. At baseline, VEGF-R1 concentrations were lower
      in PAD patients when compared with controls but did not change after SET.
      Skeletal muscle concentrations of VEGF-A are not different in PAD patients when
      compared with controls at baseline. SET is associated with a significant
      reduction in VEGF-A levels and a trend towards increased VEGF165b levels. These
      somewhat unexpected findings suggest that further investigation into the
      mechanism of vascular responses to exercise training in PAD patients is
      warranted.

PMID- 22402935
TI  - Aneurysm sac shrinkage after endovascular treatment of the aorta: beyond sac
      pressure and endoleaks.
AB  - The isolation of the aneurysm sac from systemic pressure and its consequent
      shrinkage are considered criteria of success after endovascular repair (EVAR).
      However, the process of shrinkage does not solely depend on the intrasac
      pressure, the predictive role of which remains ambiguous. This brief review
      summarizes the additional pathophysiological mechanisms that regulate the
      biomechanical properties of the aneurysm wall and may interfere with the process
      of aneurysm sac shrinkage.

PMID- 22402936
TI  - Imbalanced matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1
      activities in patients with thromboangiitis obliterans.
AB  - The pathogenic mechanisms of thromboangiitis obliterans (TAO) are not entirely
      known and the imbalance of matrix metalloproteinases (MMPs) plays a role in
      vascular diseases. We evaluated the MMP-2 and MMP-9 circulating levels and their
      endogenous tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in TAO
      patients with clinical manifestations. The study included 20 TAO patients (n = 10
      female, n = 10 male) aged 38-59 years under clinical follow-up. The patients were
      classified into two groups: (1) TAO former smokers (n = 11) and (2) TAO active
      smokers (n = 9); the control group included normal volunteer non-smokers (n = 10)
      and active smokers without peripheral artery disease (n = 10). Patient plasma
      samples were used to analyze MMP-2 and MMP-9 levels using zymography, and TIMP-1
      and TIMP-2 concentrations were determined by enzyme-linked immunosorbent assays.
      The analysis of MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios (which were used as indices
      of net MMP-2 and MMP-9 activity, respectively) showed significantly higher MMP
      9/TIMP-1 ratios in TAO patients (p < 0.05). We found no significant differences
      in MMP-2/TIMP-2 ratios (p > 0.05). We found higher MMP-9 levels and decreased
      levels of TIMP-1 in the TAO groups (active smokers and former smokers),
      especially in active smokers compared with the other groups (all p < 0.05). MMP-2
      and TIMP-2 were not significantly different in patients with TAO as compared to
      the control group (p > 0.05). In conclusion, our results showed increased MMP-9
      and reduced TIMP-1 activity in TAO patients, especially in active smokers
      compared with non-TAO patients. These data suggest that smoke compounds could
      activate MMP-9 production or inhibit TIMP-1 activity.

PMID- 22402932
TI  - Hypothalamic control of sleep in aging.
AB  - The timing of sleep and its duration are affected by circadian and homeostatic
      factors. Physiological and behavioral attributes such as the duration of previous
      wake period, food availability, temperature, and stress all affect sleep and its
      quality. As many of these physiological inputs are integrated in the
      hypothalamus, it is not surprising that this brain structure plays a crucial role
      in the regulation of sleep. I will discuss this role also in the context of
      aging, which is associated with changes in both hypothalamic function and the
      composition of sleep.

PMID- 22402937
TI  - Insulin resistance and incident peripheral artery disease in the Cardiovascular
      Health Study.
AB  - Type 2 diabetes is a risk factor for peripheral artery disease (PAD), and insulin
      resistance is a key feature of diabetes and pre-diabetes. No longitudinal
      epidemiological study has examined the relation between insulin resistance and
      PAD. Our study analyzed the association of quartiles of the homeostatic model of
      insulin resistance (HOMA-IR) and the development of PAD defined by two methods.
      PAD was first defined as the development of an abnormal ankle-brachial index
      (ABI) (dichotomous outcome) after 6 years of follow-up. PAD was alternatively
      defined as the development of clinical PAD (time-to-event analysis). The study
      samples included adults over the age of 65 years who were enrolled in the
      Cardiovascular Health Study, had fasting measurements of insulin and glucose, had
      ABI measurements, and were not receiving treatment for diabetes. Multivariable
      models were adjusted for potential confounders, including age, sex, field center
      and cohort, body mass index (BMI), smoking status, alcohol use, and exercise
      intensity. Additional models adjusted for potential mediators, including blood
      pressure, lipids, kidney function, and prevalent vascular disease. In the ABI
      analysis (n = 2108), multivariable adjusted models demonstrated a positive
      relation between HOMA-IR and incident PAD (odds ratio = 1.80 comparing the 4th
      versus 1st quartile of HOMA-IR, 95% confidence interval [CI] 1.20-2.71). In the
      clinical PAD analysis (n = 4208), we found a similar relation (hazard ratio =
      2.30 comparing the 4th versus 1st quartile of HOMA-IR, 95% CI 1.15-4.58). As
      expected, further adjustment for potential mediators led to some attenuation of
      effect estimates. In conclusion, insulin resistance is associated with a higher
      risk of PAD in older adults.

PMID- 22402939
TI  - Mammary gland development & breast cancer; connecting the dots by non-coding
      RNAs.

PMID- 22402938
TI  - Noncoding RNAs involved in mammary gland development and tumorigenesis: there's a
      long way to go.
AB  - The mammalian genome encodes thousands of noncoding RNAs. These noncoding
      transcripts are broadly categorized into short noncoding RNAs, such as microRNAs
      (miRNAs), and long noncoding RNAs (lncRNAs) of greater than 200 nt. While the
      role of miRNAs in development and cancer biology has been extensively studied,
      much less is known about the vast majority of noncoding transcripts represented
      by lncRNAs. LncRNAs are emerging as key regulators of developmental processes and
      as such, their frequent misregulation in tumorigenesis and disease in not
      unexpected. The role of lncRNAs in mammary gland development and breast cancer is
      just beginning to be elucidated. This review will discuss the role of lncRNAs in
      mammalian and mammary gland development. In addition, we will review the
      contributions of lncRNAs to the stepwise progression of tumorigenesis,
      highlighting the role of lncRNAs in breast cancer.

PMID- 22402940
TI  - Etiological [corrected] agents of rickettsiosis and anaplasmosis in ticks
      collected in Emilia-Romagna region (Italy) during 2008 and 2009.
AB  - Ticks are the main vectors of rickettsiae of the spotted fever group, as well as
      of a variety of other Rickettsiales, including bacteria of the genus Anaplasma,
      that might cause diseases in humans and animals. Here we present the result of a
      survey for ticks and for tick-associated Rickettsiales in the Emilia Romagna
      region (Northern Italy). The study was focused on ticks collected from wild
      hunted animals. Out of 392 ticks collected from these animals, 282 (72%) were
      identified as Ixodes ricinus, 110 (28%) as Dermacentor marginatus. The former was
      found on four vertebrate species, whereas the latter appeared more specific for
      wild boar. The presence of rickettsiae was demonstrated in 22.5% of I. ricinus
      (57/253) and in 29% of D. marginatus (32/110). Five ticks of the species I.
      ricinus were also positive for Anaplasma phagocytophilum (2%). In addition, we
      collected ticks by dragging in a natural park of the same region. All of the
      ticks captured by dragging were identified as I. ricinus. Thirty-six out of 200
      analyzed ticks proved positive for Rickettsia monacensis and R. helvetica (16.5
      and 1.5%, respectively). Our results highlight that that ticks present in wild
      areas, widely exploited for recreation and hunting in Emilia-Romagna, represent a
      risk for the transmission of spotted fevers and anaplasmosis to humans.

PMID- 22402941
TI  - Spatial distributions of the red palm mite, Raoiella indica (Acari:
      Tenuipalpidae) on coconut and their implications for development of efficient
      sampling plans.
AB  - The red palm mite (Raoiella indica), an invasive pest of coconut, entered the
      Western hemisphere in 2004, then rapidly spread through the Caribbean and into
      Florida, USA. Developing effective sampling methods may aid in the timely
      detection of the pest in a new area. Studies were conducted to provide and
      compare intra tree spatial distribution of red palm mite populations on coconut
      in two different geographical areas, Trinidad and Puerto Rico, recently invaded
      by the mite. The middle stratum of a palm hosted significantly more mites than
      fronds from the upper or lower canopy and fronds from the lower stratum, on
      average, had significantly fewer mites than the two other strata. The mite
      populations did not vary within a frond. Mite densities on the top section of the
      pinna had significantly lower mite densities than the two other sections, which
      were not significantly different from each other. In order to improve future
      sampling plans for the red palm mite, the data was used to estimate the variance
      components associated with the various levels of the hierarchical sampling
      design. Additionally, presence-absence data were used to investigate the
      probability of no mites being present in a pinna section randomly chosen from a
      frond inhabited by mites at a certain density. Our results show that the most
      precise density estimate at the plantation level is to sample one pinna section
      per tree from as many trees as possible.

PMID- 22402943
TI  - Drosophila: a model for understanding obesity and diabetic complications.
AB  - The molecular mechanisms underlying development of obesity and diabetic
      complications are not well understood. Drosophila has become a popular model
      organism for studying a variety of human diseases. We discuss here emerging
      Drosophila models of obesity and diabetic complications.

PMID- 22402942
TI  - Phase II study of bevacizumab and erlotinib in the treatment of advanced
      hepatocellular carcinoma patients with sorafenib-refractory disease.
AB  - BACKGROUND: The combination of bevacizumab (B) and erlotinib (E) has shown
      promising clinical outcomes as the first-line treatment of advanced HCC patients.
      We aimed to evaluate the efficacy and safety of using combination of B + E in
      treating advanced HCC patients who had failed prior sorafenib treatment. METHODS:
      Eligible advanced HCC patients with documented radiological evidence of disease
      progression with sorafenib treatment were recruited. All patients received
      bevacizumab(B) at 10 mg/kg every 2 weeks with erlotinib(E) at 150 mg daily for a
      maximum of 6 cycles. Response assessments using both RECIST and modified RECIST
      criteria were performed after every 6 weeks. The primary endpoint was clinical
      benefit (CB) rate and a Simon two-stage design was employed. RESULTS: The trial
      was halted in the first stage according to the pre-set statistical criteria with
      10 patients recruited. The median age was 47 years (range, 28-61) and all
      patients were in ECOG performance status 1. Eighty percent of patients were
      chronic hepatitis B carriers and all patients had Child A cirrhosis. Among these
      10 patients, none of the enrolled patients achieved response or stable disease.
      The median time-to-progression was 1.81 months (95 % confidence interval [C.I.],
      1.08-1.74 months) and overall survival was 4.37 months (95 % C.I., 1.08-11.66
      months). Rash (70 %), diarrhea (50 %) and malaise (40 %) were the most commonly
      encountered toxicities. CONCLUSION: The combination of B + E was well tolerated
      but had no activity in an unselected sorafenib-refractory advanced HCC
      population. Condensed abstract The combination of bevacizumab and erlotinib had
      no clinical activity in sorafenib-refractory HCC population.

PMID- 22402944
TI  - Macrovascular disease in diabetes: is the mouse a suitable model?
AB  - To elucidate the pathogenesis of macrovascular disease in diabetes, animal models
      are widely used. Diabetic mice are of particular interest because they can be
      crossed to knockout mice lacking specific genes that are under consideration to
      contribute to diabetic vascular complications. However, the mouse is relative
      resistant to develop atherosclerosis. Therefore, we review some commonly used
      mouse models and discuss their advantages and disadvantages.

PMID- 22402945
TI  - Murine models of diabetic nephropathy.
AB  - Diabetic nephropathy is the leading cause of end stage renal diseases worldwide.
      Even though several diabetic animal models exist, not a single one develops renal
      changes sufficiently reflecting those seen in humans. This review provides an
      overview on mouse models presenting with various features of diabetic
      nephropathy. The critical analysis and comparison of existing mouse models
      substantially enhances our understanding of the disease process and should
      provide a guide for choosing the most suitable mouse model for the investigation
      of diabetic nephropathy.

PMID- 22402946
TI  - Critical evaluation of mouse models used to study pain and loss of pain
      perception in diabetic neuropathy.
AB  - A number of studies have addressed diabetic neuropathy (DN) in transgenic and
      knock out mouse models to unravel the molecular mechanisms underlying metabolic
      pain and loss of pain perception. However, it is difficult to compare these
      studies with each other or even with human DN due to experimental differences
      including the type of diabetes, the background strain of the respective mouse
      model, the methods of diabetes induction and the duration of diabetes, animal age
      and gender. To receive useful information for DN from genetically modified mice,
      it is therefore mandatory to first define the appropriate model and - if
      necessary - to backcross transgenic strains into the respective background to
      allow a reliable (and at least in part translatable to human DN) interpretation
      of the results.

PMID- 22402947
TI  - Glucose effects on the peritoneum: what can we learn from rodent models?
AB  - During long-term peritoneal dialysis (PD) the peritoneal membrane underlies
      processes of structural and functional reorganization mediated by high glucose
      and reactive glucose metabolites that are contained in PD solutions; this process
      is accompanied by increasing fibrosis. Mechanistically, the peritoneal damage is
      triggered by the interaction of advanced glycation end-products with their
      receptor; this is true for rodents as well as for humans. With this knowledge
      interventional strategies can be tested in rodent models, among them are the
      lipid soluble vitamin B1 analogue benfotiamine (BF) or detoxifying enzymes such
      as glyoxalase. Of additional interest is the finding that PD fluids do not only
      cause local but also systemic damage, in particular renal and cardiovascular. In
      the case of kidney damage, the intervention with BF was also successful. Taken
      together, PD can be regarded as a local model for long-term diabetes together
      with systemic aspects of damage.

PMID- 22402948
TI  - Yeast as a model to understand mechanisms and consequences of protein
      modifications by metabolism derived toxic products.
AB  - An inevitable consequence of metabolism in cells across all kingdoms of life is
      the non-enzymatic formation of toxic metabolites such as reactive oxygen species
      (ROS) and reducing sugars, whose reaction products are associated with several
      diseases such as clinical complications of diabetes, cataracts, cancer and age
      related late-onset diseases like Parkinson's Disease and Alzheimer's Disease,
      amongst others. Yeast has been used successfully to study the reaction of these
      toxic metabolites with proteins in vivo, which I will summarize with exemplified
      studies on 2 crucial reactions, protein carbonylation and protein glycation.

PMID- 22402949
TI  - Liver: a target of late diabetic complications.
AB  - Whereas many studies have implicated metabolic liver dysfunction as a causative
      factor for obesity-related type 2 diabetes and the Metabolic Syndrome, its role
      as a long-term complication of diabetic metabolism is still mostly unexplored.In
      contrast to the well-described late diabetic micro- and macro-vascular
      complications in response to hyperglycemic conditions such as nephro- and
      retinopathy as well as atherosclerosis, only recent studies have highlighted
      disturbances of liver function as a novel aspect of diabetic late complications
      that may substantially impact the overall disease outcome and determine mortality
      rates in diabetic subjects. Here we will discuss recent developments in this
      area, particularly focusing on transcriptional regulators of hepatic dysfunction
      as a long-term consequence of established diabetes.

PMID- 22402950
TI  - Crosstalk in the retinal neurovascular unit - lessons for the diabetic retina.
AB  - Diabetic retinopathy shares important features with neurodegenerative retinal
      diseases, including loss of ganglion cells and retinal thinning. The impact on
      vasoregression and subsequent ischemia-driven changes such as macular edema and
      proliferative retinopathy are not established. Studies using adult
      neurodegenerative animal models such as the transgenic TGR(CMV-PKD2(1/703)HA) rat
      imply early activation of the innate immunity system and the complement system as
      well as microglia playing a role in the damage of the retinal neurovascular unit.

PMID- 22402951
TI  - Understanding diabetic polyneuropathy and longevity: what can we learn from the
      nematode Caenorhabditis elegans?
AB  - Pathogenesis of late diabetic complications is influenced by a complex interplay
      of multiple exogenous and intrinsic factors. The well characterised nematode
      Caenorhabditis elegans is an ideal model to study causes of diabetic
      polyneuropathy because of its easily accessible nervous system. A repertoire of
      methods allows the assessment of both morphological and functional glucotoxic
      damages as well as reduction of lifespan, thereby helping to examine the
      influence of different pathways and mechanisms on neurodegeneration. Its insulin
      signalling system allows to directly visualize effects of insulin on high glucose
      induced neuronal damage, leading to a better understanding of diabetic
      polyneuropathy.

PMID- 22402952
TI  - Zebrafish: a model for understanding diabetic complications.
AB  - Diabetes mellitus causes several vascular complications in patients, such as
      macrovascular problems including myocardial infarction, peripheral artery
      diseases and stroke and microvascular problems including nephropathy and
      retinopathy. Likewise, diabetes mellitus is associated with other complications
      such as neuropathy and delayed wound healing. The zebrafish has been used for
      decades as a model organism for studies in developmental biology. In fact several
      common and important developmental mechanisms have been identified in zebrafish
      which are similar in mammals. The zebrafish has short generation intervals and
      zebrafish embryos are transparent and therefore provide unique imaging
      opportunities. In combination with genetic manipulations, including gene
      silencing protocols by using morpholinos, mutant or transgenic fish lines, the
      zebrafish has become one of the most important models in developmental biology.
      Over and above, zebrafish is also an established model organism for several
      pathophysiological conditions which are related to human diseases. For instance,
      zebrafish is used as an inflammation and regeneration model because of its
      ability to partially compensate for organ loss (e. g., heart and fins). It is
      also used for drug screening, in tumor biology, for systems biology, congenital
      and hereditary disease, and in infection [1].

PMID- 22402954
TI  - Effect of vitamin C on morphine use after laparoscopic cholecystectomy: a
      randomized controlled trial.
AB  - PURPOSE: We designed a randomized double-blind placebo-controlled trial to assess
      the role of a single prophylactic dose of vitamin C (2 g) po in reducing the
      consumption of opioids postoperatively in patients undergoing laparoscopic
      cholecystectomy. METHODS: Eighty adult patients were allocated to receive 2 g
      vitamin C po or placebo approximately one hour prior to induction of anesthesia.
      Following laparoscopic cholecystectomy, patients received morphine patient
      controlled analgesia for 24 hr. The following data were assessed postoperatively
      in the postanesthesia care unit at two, four, six, 12, and 24 hr: morphine
      consumption, verbal numerical rating scale scores for incisional pain and
      nausea/vomiting, and pruritus and sedation scores. The primary outcome measure
      was 24-hr morphine consumption. Patient satisfaction was assessed before hospital
      discharge. RESULTS: Morphine consumption was significantly lower in the vitamin C
      group vs the placebo group [16.2 (10.7) and 22.8 (13.8) mg, respectively;
      difference = 6.6 mg; 95% confidence interval, 1.1 to 12.1 mg; P = 0.02]. There
      was no difference in pain scores or side effects between the two groups.
      Satisfaction scores were similar in both groups. CONCLUSION: Our study showed
      that supplementation with vitamin C (2 g) po decreased morphine consumption in
      the postoperative period in patients undergoing laparoscopic cholecystectomy.

PMID- 22402955
TI  - Effect of Roux-en-Y gastric bypass vs sleeve gastrectomy on glucose and gut
      hormones: a prospective randomised trial.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the most common
      bariatric technique. Laparoscopic sleeve gastrectomy (LSG) is a restrictive
      procedure; the metabolic and endocrine effects of which remain unknown. We
      compared the effects of both procedures on glucose metabolism and fasting and
      meal-stimulated gut hormone levels. METHODS: Seven patients were randomised to
      LRYGB and eight to LSG. All patients were evaluated before and at 3 and 12 months
      postoperatively. Plasma levels of glucose, insulin, ghrelin, leptin, peptide YY
      (PYY), GLP-1 and pancreatic polypeptide were measured before and after 10 and 60
      min of a standard test meal ingestion. RESULTS: Age, body mass index and
      preoperative hormone levels were similar in both groups. A significant reduction
      of plasma glucose and insulin levels was observed after surgery. Moreover, a
      normalisation of homeostatic model assessment for insulin resistance value was
      also seen after both procedures. The fasting and postprandial leptin levels were
      significantly lower in the LRYGB group. LSG was followed by a significant
      reduction in fasting ghrelin levels. In the LRYGB group, GLP-1 levels increased
      significantly after the test meal. CONCLUSIONS: LRYGB and LSG markedly improved
      glucose homeostasis. Only LSG decreased fasting and postprandial ghrelin levels,
      whereas GLP-1 and PYY levels increased similarly after both procedures.

PMID- 22402956
TI  - Acute appendicitis and adverse pregnancy outcomes: a nationwide population-based
      study.
AB  - BACKGROUND/OBJECTIVE: Acute appendicitis is the most common non-obstetric
      surgical procedure in pregnant women. Using two large-scale nationwide population
      based datasets, this study aimed to assess the risk of adverse pregnancy outcomes
      between mothers with and without appendicitis in Taiwan. METHODS: This study used
      two nationwide population-based datasets: the Taiwan National Health Insurance
      Research Dataset and the Taiwan national birth certificate registry. This study
      included 908 women who had live singleton births and who had been hospitalized
      with a diagnosis of acute appendicitis, and another randomly selected 4,540 women
      as a comparison group. Conditional logistic regression analyses were performed to
      calculate the risk of adverse pregnancy outcomes including low birth weight
      (LBW), preterm birth, small for gestational age (SGA), cesarean section (CS),
      congenital anomalies, Apgar scores at 5 min (<7), and pre-eclampsia/eclampsia.
      RESULTS: The adjusted odds ratios for LBW, preterm birth, SGA, CS, and congenital
      anomalies in women with acute appendicitis were 1.82 (95 % CI = 1.43-2.30), 1.59
      (95 % CI = 1.25-2.02), 1.33 (95 % CI = 1.12-1.60), 1.24 (95 % CI = 1.07-1.44),
      and 2.07 (95 % CI = 1.07-4.03), respectively, compared with women without acute
      appendicitis after adjusting for highest maternal educational level, marital
      status, geographic region, gestational diabetes, gestational hypertension,
      coronary heart disease, anemia, hyperlipidemia, obesity, and alcohol
      abuse/alcohol dependence syndrome, infant sex and parity, and paternal age.
      CONCLUSIONS: There were increased risks for having LBW, preterm infants, SGA,
      congenital anomalies, and for experiencing CS among women with acute appendicitis
      than comparison women.

PMID- 22402957
TI  - Effect of surgical approach on 30-day mortality and morbidity after elective
      colectomy: a NSQIP study.
AB  - PURPOSE: The aim of this study was to evaluate the laparoscopic approach and pre-
      and postoperative conditions as predictors of 30-day mortality and morbidity in
      elective colectomy. METHODS: Elective colectomies were identified in the 2005
      2008 American College of Surgeons National Surgical Quality Improvement Program
      database. Multivariate logistic regression was used to model 30-day mortality and
      morbidity following elective colectomy. Propensity scores were calculated to
      decrease selection bias. RESULTS: During the period studied, 14,321 patients
      underwent open colectomy and 10,409 underwent laparoscopic colectomy. Factors
      that significantly influenced mortality included male gender [odds ratio (OR)
      1.4, confidence interval (CI) 1.07-1.9]; age (OR 1.07, CI 1.05-1.08);
      comorbidities including dyspnea, ascites, congestive heart failure, dialysis, or
      disseminated cancer; and postoperative conditions including reintubation (OR 2.6,
      CI 1.6-4.0), renal failure (OR 3.8, CI 2.1-6.9), stroke (OR 6.44, CI 2.4-17.6),
      and septic shock (OR 13.1, CI 8.76-19.4). While laparoscopy was not independently
      associated with mortality, it was associated with decreased postoperative
      morbidity including reintubation (OR 0.74, CI 0.59-0.91), renal failure (OR 0.60,
      CI 0.4-0.91), septic shock (OR 0.74, CI 0.59-0.92), wound infection (OR 0.58,
      CI0.44-0.77), and pneumonia (OR 0.71, CI 0.59-0.86). CONCLUSIONS: Based on this
      analysis, laparoscopy was associated with a decrease in 30-day postoperative
      morbidity for colectomy. However, after adjusting for preoperative comorbidities
      and postoperative morbidities, laparoscopy did not independently influence
      mortality after colectomy.

PMID- 22402959
TI  - Psychometric properties of the Farsi version of effort-reward imbalance
      questionnaire: a longitudinal study in employees of a synthetic fibre factory in
      Iran.
AB  - PURPOSE: To assess the reliability and validity of the Farsi version of the
      effort-reward imbalance questionnaire (F-ERIQ) and to examine the responsiveness
      of the tool to changes over time. METHODS: A longitudinal study was carried out
      among 227 male employees of Iran Polyacryl Corporation. The F-ERIQ was developed
      through a forward-backward translation process that includes three scales of
      effort, reward and over-commitment (OC). Reliability and internal consistency of
      the F-ERIQ were assessed by split-half and Cronbach's alpha coefficients.
      Confirmatory factor analysis, convergent and discriminant validity were conducted
      to evaluate construct validity. Depressive mood was used as an indicator for
      exploring criterion validity. The variations in mean scores over time for scales
      were regarded as measures of the responsiveness to changes. RESULTS: Baseline
      split-half correlations for effort, reward and OC were 0.53, 0.85 and 0.65,
      respectively; Cronbach's alpha coefficients improved from 0.61 to 0.70 for
      effort, 0.85 to 0.88 for reward and 0.67 to 0.72 for OC. All of item-total
      correlations were higher than 0.23 and item-scales correlations were higher than
      0.4. Although Values of Goodness of Fit Index and Adjusted GFI were higher than
      0.9 and Root Mean Square Error of Approximation, Root Mean Square Residual and
      Standardized RMR were lower than 0.05, confirmatory factor analysis only
      confirmed the construct of the effort and OC. People with higher job stress were
      at higher risk of depressive mood (at least 3 times more). Overall, the mean
      score of effort, OC and ERI increase, and the figures decrease for reward among
      people who experience changes. CONCLUSIONS: These findings provide evidence that
      the F-ERIQ is a reliable and valid instrument for assessing psychosocial stress
      at work among Farsi-speaking male employees. We propose that F-ERIQ be further
      evaluated across a variety of jobs and industries.

PMID- 22402961
TI  - Characterization of cumulus expansion-inhibiting factor (CEIF) in goat follicles.
AB  - Studies suggest that oocyte cumulus expansion is regulated by both cumulus
      expansion-enabling factor (CEEF) and cumulus expansion-inhibiting factors (CEIF).
      Many reports on CEEF have appeared, but CEIF has rarely been studied. By cumulus
      expansion assays using mouse cumulus-oocyte complexes (COCs) and oocytectomized
      complexes, the present study demonstrated that whereas follicular fluid (FF) from
      medium (diameter, 2-4 mm) goat follicles contained both CEEF and CEIF activities,
      FF from large (diameter, 5-6 mm) abattoir or large (diameter, 5-7 mm) follicle
      stimulating hormone (FSH)-stimulated follicles contained neither. FF from
      (diameter, 5-7 mm) human chorionic gonadotropin-stimulated follicles showed CEEF
      but not CEIF activity. Whereas medium conditioned with cumulus or mural granulosa
      cells from medium goat follicles contained only CEEF activity, theca cell
      conditioned medium (CM) showed both CEEF and CEIF activities. Whereas 0.01 mg/ml
      of heparin efficiently inhibited cumulus expansion of mouse COCs in vitro, FF
      from large follicles that showed no CEIF activity contained much higher
      concentrations (0.23-0.25 mg/ml) of heparin. None of the glycosaminoglycans
      (GAGs) tested inhibited cumulus expansion of goat COCs. Among the follicles
      observed, only FF from medium goat follicles contained a linoleic acid (LA) level
      sufficient to inhibit cumulus expansion of both mouse and goat COCs in vitro. CM
      contained some amount of GAGs but no LA. Taken together, the results suggest that
      1) the FSH and luteinizing hormone (LH) surges before ovulation promote cumulus
      expansion by down-regulating CEIF and up-regulating CEEF activity, respectively;
      2) GAGs are not the CEIF in goat follicles; and 3) LA has CEIF activity but
      additional factors must be involved, because CM that showed high CEIF activity
      contained no LA.

PMID- 22402962
TI  - Of mice and (wo)men: purified oogonial stem cells from mouse and human ovaries.

PMID- 22402960
TI  - Exposure to bleomycin, etoposide, and cis-platinum alters rat sperm chromatin
      integrity and sperm head protein profile.
AB  - Testicular cancer, currently the most common cancer affecting men of reproductive
      age, is one of the most curable malignancies due to the progress made in the
      early diagnosis and effective treatment of this disease. The coadministration of
      bleomycin, etoposide, and cis-platinum (BEP) has brought the 5-yr survival rate
      of testis cancer patients to over 90%. However, this treatment results in
      reproductive chemotoxic effects. We assessed the effect of BEP treatment on sperm
      chromatin integrity and sperm head protein profiles of adult male Brown Norway
      rats following 9 wk of treatment with BEP and in animals treated for 9 wk and
      then subjected to a 9-wk recovery period. Both the susceptibility of DNA to
      denaturation and the number of strand breaks were significantly increased in
      mature sperm following 9 wk of treatment with BEP; proteomic analysis revealed
      that the expression of several proteins, including HSP90AA1 and HSP90B1, was
      markedly affected. Following a 9-wk recovery period, mature sperm did not show
      significant DNA damage, indicating that repair had potentially occurred.
      Interestingly, the protamination level of the sperm of these animals was
      significantly decreased, while histones HIST1H1D (H1.2), HIST1H4B (H4),
      HIST2H2AA3 (H2A1), and HIST1H2BA (H2B1A) were concomitantly up-regulated; this
      was not observed in the sperm immediately following 9 wk of treatment. Thus,
      there are persistent effects on proteins in sperm heads from the cauda
      epididymidis 9 wk posttreatment, in the absence of DNA strand breaks. We suggest
      that these effects on the sperm head proteome may contribute to long-lasting
      adverse effects in the progeny of BEP-exposed males.

PMID- 22402958
TI  - Gender and survival in patients with heart failure: interactions with diabetes
      and aetiology. Results from the MAGGIC individual patient meta-analysis.
AB  - AIM: The aim of this study was to investigate the relationship between gender and
      survival of patients with heart failure, using data from both randomized trials
      and observational studies, and the relative contribution of age, left ventricular
      systolic function, aetiology, and diabetes to differences in prognosis between
      men and women. METHODS AND RESULTS: Data from 31 studies (41 949 patients; 28 052
      men, 13 897 women) from the Meta-Analysis Global Group In Chronic Heart Failure
      (MAGGIC) individual patient meta-analysis were used. We performed survival
      analysis to assess the association of gender with mortality, adjusting for
      predictors of mortality, including age, reduced or preserved ejection fraction
      (EF), and ischaemic or non-ischaemic aetiology. Women were older [70.5 ( standard
      deviation 12.1) vs. 65.6 (standard deviation 11.6) years], more likely to have a
      history of hypertension (49.9% vs. 40.0%), and less likely to have a history of
      ischaemic heart disease (46.3% vs. 58.7%) and reduced EF (62.6% vs. 81.6%)
      compared with men. During 3 years follow-up, 3521 (25%) women and 7232 (26%) men
      died. After adjustment, male gender was an independent predictor of mortality,
      and the better prognosis associated with female gender was more marked in
      patients with heart failure of non-ischaemic, compared with ischaemic, aetiology
      (P-value for interaction = 0.03) and in patients without, compared with those
      with, diabetes (P-value for interaction <0.0001). CONCLUSION: This large,
      individual patient data meta-analysis has demonstrated that survival is better
      for women with heart failure compared with men, irrespective of EF. This survival
      benefit is slightly more marked in non-ischaemic heart failure but is attenuated
      by concomitant diabetes.

PMID- 22402964
TI  - Epithelial-to-mesenchymal transition in granulosa cells: a key to activation of
      follicle growth?

PMID- 22402963
TI  - Overactivation of hedgehog signaling alters development of the ovarian
      vasculature in mice.
AB  - The hedgehog (HH) signaling pathway is critical for ovarian function in
      Drosophila, but its role in the mammalian ovary has not been defined. Previously,
      expression of a dominant active allele of the HH signal transducer protein
      smoothened (SMO) in Amhr2(cre/+)SmoM2 mice caused anovulation in association with
      a lack of smooth muscle in the theca of developing follicles. The current study
      examined events during the first 2 wk of life in Amhr2(cre/+)SmoM2 mice to gain
      insight into the cause of anovulation. Expression of transcriptional targets of
      HH signaling, Gli1, Ptch1, and Hhip, which are used as measures of pathway
      activity, were elevated during the first several days of life in
      Amhr2(cre/+)SmoM2 mice compared to controls but were similar to controls in older
      mice. Microarray analysis showed that genes with increased expression in 2-day
      old mutants compared to controls were enriched for the processes of vascular and
      tube development and steroidogenesis. The density of platelet endothelial cell
      adhesion molecule (PECAM)-labeled endothelial tubes was increased in the cortex
      of newborn ovaries of mutant mice. Costaining of preovulatory follicles for PECAM
      and smooth muscle actin showed that muscle-type vascular support cells are
      deficient in theca of mutant mice. Expression of genes for steroidogenic enzymes
      that are normally expressed in the fetal adrenal gland were elevated in newborn
      ovaries of mutant mice. In summary, overactivation of HH signaling during early
      life alters gene expression and vascular development and this is associated with
      the lifelong development of anovulatory follicles in which the thecal vasculature
      fails to mature appropriately.

PMID- 22402965
TI  - Immunolocalization of adipocytes and prostaglandin E2 and its four receptor
      proteins EP1, EP2, EP3, and EP4 in the caprine cervix during spontaneous term
      labor.
AB  - The mechanisms of cervical ripening and dilation in mammals remain obscure.
      Information is lacking about the localization of prostaglandin E(2) (PGE(2))
      producing cells and PGE(2) receptors (EP) in intrapartum cervix and whether
      cervical dilation at parturition is an active process. To reveal these
      mechanisms, immunolocalization of EP1-EP4 (official gene symbols PTGER1-PTGER4)
      and PGE(2)-producing cells in caprine cervix during nonpregnancy, pregnancy, and
      parturition was assayed by immunohistochemistry (IHC); the mRNA expression levels
      of PTGS2, PTGER2 (EP2), and PTGER4 (EP4) were determined using quantitative PCR;
      and the existence of adipocytes in the cervix at various stages was demonstrated
      with Oil Red O staining and IHC of perilipin A. The results suggested that in
      intrapartum caprine cervix staining of the PGE(2) was observed in the overall
      tissues, for example, blood vessels, canal or glandular epithelia, serosa,
      circular and longitudinal muscles, and stroma in addition to adipocytes; EP2 was
      detectable in all the tissues other than glandular epithelia; EP4 was strongly
      expressed in all the tissues other than serosa; EP1 was detected mainly in
      arterioles and canal or glandular epithelia; and EP3 was poorly expressed only in
      stroma, canal epithelia, and circular muscles. Little or no expression of EP2,
      EP3, and EP4 as well as PGE(2) in all cervical tissues was observed during
      nonpregnancy and pregnancy except for the strong expression of EP1 in canal or
      glandular epithelia during pregnancy. The mRNA expression levels of PTGS2,
      PTGER2, and PTGER4 were significantly higher in intrapartum than nonpregnant and
      midpregnant cervices (P < 0.01). Adipocytes appear only in the intrapartum
      cervix. These results support the concept that PGE(2) modulates specific
      functions in various anatomical structures of the caprine cervix at labor and the
      appearance of adipocytes at labor is likely related to caprine cervical dilation.

PMID- 22402966
TI  - Growing fast or slow: what makes the best embryo?

PMID- 22402967
TI  - Identification of label-retaining perivascular cells in a mouse model of
      endometrial decidualization, breakdown, and repair.
AB  - The human endometrium is incredibly dynamic, undergoing monthly cycles of growth
      and regression during a woman's reproductive life. Endometrial repair at the
      cessation of menstruation is critical for reestablishment of a functional
      endometrium receptive for embryo implantation; however, little is understood
      about the mechanisms behind this rapid and highly efficient process. This study
      utilized a functional mouse model of endometrial breakdown and repair to assess
      changes in endometrial vasculature that accompany these dynamic processes. Given
      that adult endometrial stem/progenitor cells identified in human and mouse
      endometrium are likely contributors to the remarkable regenerative capacity of
      endometrium, we also assessed label-retaining cells (LRC) as candidate stromal
      stem/progenitor cells and examined their relationship with endometrial
      vasculature. Newborn mouse pups were pulse-labeled with bromodeoxyuridine (BrdU)
      and chased for 5 wk before decidualization, endometrial breakdown, and repair
      were induced by hormonal manipulation. Mean vessel density did not change
      significantly throughout breakdown and repair; however, significantly elevated
      endothelial cell proliferation was observed in decidual tissue. Stromal LRC were
      identified throughout breakdown and repair, with significantly fewer observed
      during endometrial repair than before decidualization. A significantly higher
      percentage of LRC were associated with vasculature during repair than before
      decidualization, and a proportion were undergoing proliferation, indicative of
      their functional capacity. This study is the first to examine the endometrial
      vasculature and candidate stromal stem/progenitor cells in a functional mouse
      model of endometrial breakdown and repair and provides functional evidence
      suggesting that perivascular LRC may contribute to endometrial stromal expansion
      during the extensive remodeling associated with this process.

PMID- 22402968
TI  - Challenges of surgery in developing countries: a survey of surgical and
      anesthesia capacity in Uganda's public hospitals.
AB  - BACKGROUND: There are large disparities in access to surgical services due to a
      multitude of factors, including insufficient health human resources,
      infrastructure, medicines, equipment, financing, logistics, and information
      reporting. This study aimed to assess these important factors in Uganda's
      government hospitals as part of a larger study examining surgical and anesthesia
      capacity in low-income countries in Africa. METHODS: A standardized survey tool
      was administered via interviews with Ministry of Health officials and key health
      practitioners at 14 public government hospitals throughout the country.
      Descriptive statistics were used to analyze the data. RESULTS: There were a total
      of 107 general surgeons, 97 specialty surgeons, 124 obstetricians/gynecologists
      (OB/GYNs), and 17 anesthesiologists in Uganda, for a rate of one surgeon per
      100,000 people. There was 0.2 major operating theater per 100,000 people.
      Altogether, 53% of all operations were general surgery cases, and 44% were OB/GYN
      cases. In all, 73% of all operations were performed on an emergency basis. All
      hospitals reported unreliable supplies of water and electricity. Essential
      equipment was missing across all hospitals, with no pulse oximeters found at any
      facilities. A uniform reporting mechanism for outcomes did not exist.
      CONCLUSIONS: There is a lack of vital human resources and infrastructure to
      provide adequate, safe surgery at many of the government hospitals in Uganda. A
      large number of surgical procedures are undertaken despite these austere
      conditions. Many areas that need policy development and international
      collaboration are evident. Surgical services need to become a greater priority in
      health care provision in Uganda as they could promise a significant reduction in
      morbidity and mortality.

PMID- 22402969
TI  - Utility of the Surgical Apgar Score in a district general hospital.
AB  - BACKGROUND: The Surgical Apgar Score (SAS) is a simple tool for intraoperative
      risk stratification. The aim of this prospective observational study was to
      assess its performance in predicting outcome after general/vascular and
      orthopedic surgery and its utility in a U.K. district general hospital. METHOD: A
      prospective cohort of 223 consecutive general, vascular, and orthopedic surgical
      cases was studied. The SAS was calculated for all patients, and its relationship
      to 30 day mortality and major complication assessed with reference to the mode of
      surgery (elective or emergent). Statistical analysis of categorical data was
      performed with Fisher's exact test and the AUC (area under the curve) on receiver
      operating characteristic (ROC) analysis. Selected cases were reviewed to assess
      the potential of the SAS to modify postoperative management. RESULTS: The
      proportion of patients who died or experienced major complications increased
      monotonically with Surgical Apgar Score category in general and vascular but not
      orthopedic cases. The relative risks of mortality or major complication between
      SAS categories were less marked than in previous publications. The SAS performed
      variably on ROC curve analysis, with an AUC of 0.62-0.73. Discrimination achieved
      significance in general and vascular cases (p = 0.0002) but not in orthopedic
      cases (p = 0.15). Subgroup analysis of high (SAS < 7) and low risk (SAS >= 7)
      groups demonstrated utility of the score in general surgery and vascular cases
      overall (p < 0.0001), and in the emergency (p = 0.004) but not elective (p =
      0.12) subgroups. Case note review of those patients who died indicated that
      despite their identification by the SAS, there would have been limited scope to
      modify outcome. CONCLUSION: This study provides further evidence that the SAS is
      a simple and effective predictive tool in the emergency general and vascular
      surgical setting. It appears to have a limited role in the management of
      individual patients after orthopedic surgery and elective general/vascular
      surgery. The SAS has been proven to reliably stratify risk in larger populations
      and might be applied most usefully as a marker of quality. Further studies are
      required to determine whether its application can influence outcome.

PMID- 22402970
TI  - Resection and primary anastomosis without diverting ileostomy for left colon
      emergencies: is it a safe procedure?
AB  - INTRODUCTION: Large-bowel obstruction and perforation are still frequently
      occurring entities for the acute care surgeon. In these cases, Hartmann's
      procedure is the most commonly used surgical technique. However, recent papers
      demonstrate that colon resection and primary anastomosis (RPA) in the emergency
      setting is a safe and feasible procedure. We present our series of left colon
      resection and primary anastomosis procedures from Torrevieja Hospital (Alicante,
      Spain), performed without bowel irrigation or a diverting ileostomy. MATERIALS
      AND METHODS: Thirty-two RPA procedures were performed in emergency settings for
      perforation or obstruction, or both, during an 18-month period. The following
      data were prospectively collected: age, gender, nationality, diagnoses, ASA
      score, body mass index (BMI), POSSUM score (Physiological and Operative Severity
      Score for the enumeration of Mortality and morbidity), and the score according to
      the Hinchey classification. Furthermore, duration of the operation, length of
      postoperative hospital stay, and mortality and morbidity data were recorded.
      RESULTS: Sixteen of these patients were diagnosed with acute diverticulitis, 14
      patients with neoplasm (of which 9 cases had obstruction, 2 cases had
      perforation, and 3 cases had both), and foreign body perforation in the remaining
      2 cases. The mean hospital stay was 7.8 (range, 4-10) days. The physiological
      POSSUM score was 24.4 (range, 15-39), and the surgical POSSUM score was 19.8
      (range, 16-24). None of the patients died (0% mortality). Seven patients
      developed some kind of complication (21.9%), all of which were managed
      conservatively. CONCLUSIONS: The results of this study suggest that RPA for left
      colon obstruction and perforation in emergency settings can be safely performed
      in certain surgical conditions.

PMID- 22402971
TI  - Restricted intravenous fluid regimen reduces the rate of postoperative
      complications and alters immunological activity of elderly patients operated for
      abdominal cancer: a randomized prospective clinical trail.
AB  - BACKGROUND: Perioperative fluid restriction can lead to better clinical outcomes
      and reduced complications. However, whether perioperative fluid restriction can
      alter the patient's postoperative cellular immunity is unknown. Therefore, a
      randomized, prospective clinical study was designed to determine whether fluid
      restriction improves immunological outcome in elderly patients who undergo
      gastrointestinal surgery for cancer removal. METHODS: A total of 179 patients
      aged 65 years or older were recruited for the study and were randomly assigned to
      receive the restricted fluid regimen (R group) or the standard fluid regimen (S
      group). Postoperative T-lymphocyte subpopulations (CD3(+), CD4(+), and CD8(+))
      frequencies and monocyte HLA-DR expression was investigated. Perioperative
      complications and cellular immunity changes were analyzed comparatively between
      the two groups. RESULTS: The restricted intravenous fluid regimen was associated
      with significantly less postoperative complications (1.5 complications/patient
      vs. S group: 2.2 complications/patient), especially for infection complications
      (15% vs. S group: 27%, p = 0.04). Circulating CD3(+) T-cells were suppressed
      after surgery in both treatment groups, but the cell frequency (cell/MUL) was
      higher in the R group (746 vs. S group: 480 at postoperative day (POD) 2, p =
      0.022; 878 vs. 502 at POD 3, p = 0.005; 892 vs. 674 at POD 5, p = 0.042).
      Similarly, the HLA-DR expression (% of all T cells) in monocytes were decreased
      in both groups, but the expression remained higher in the R group (66.20 vs. S
      group: 51.97 at POD 1, p = 0.029; 68.19 vs. 51.26 at POD 2, p = 0.039; 72.19 vs.
      57.45 at POD 3, p = 0.014; 73.92 vs. 60.46 at POD 5, p = 0.036). Multivariate
      analysis suggested that perioperative CD3(+) T cell changes were associated with
      the development of postoperative complications [odds ratio (OR) = 1.963; 95%
      confidence interval (CI) 1.019-3.782; p = 0.044] and postoperative infections (OR
      = 3.106; 95% CI 1.302-7.406; p = 0.011). CONCLUSIONS: In elderly gastrointestinal
      cancer patients, cellular immunity is better preserved by the perioperative fluid
      restriction regimen. The better preserved cellular immunological function is
      correlated with a reduced perioperative complications rate.

PMID- 22402972
TI  - A novel definition of extrathyroidal invasion for patients with papillary thyroid
      carcinoma for predicting prognosis.
AB  - OBJECTIVES: Extrathyroidal invasion is one of the most significant risk factors
      for patients with papillary thyroid carcinoma (PTC). The purpose of this study
      was to evaluate a novel definition of extrathyroidal invasion for patients with
      PTC as a method for predicting a patient's prognosis. METHODS: The prospective
      study was conducted for consecutive 930 patients with primary PTC who received
      surgery during 1993-2009. We defined only patients who had preoperative recurrent
      laryngeal nerve palsy or patients in whom the tumor had invaded to the mucosa of
      the trachea and/or esophagus as Ex3. Patients with minimal invasion were
      classified as Ex1, and patients with massive invasion, when we could shave off
      the tumors, were classified as Ex2. Patients without extrathyroidal invasion were
      classified as Ex0. RESULTS: Patients classified Ex3 showed significantly shorter
      disease-free survival (p = 0.03) and disease-specific survival (p = 0.007) than
      patients classified Ex2. The time to recurrence at resection sites was shorter in
      patients classified Ex3 than in patients classified Ex2 (p = 0.02). The time to
      death due to distant metastasis of patients classified Ex3 was significantly
      shorter than that of patients classified Ex2 (p = 0.02). Within the patients
      classified Ex3, disease-specific survival of patients with invasion to other
      nearby structures was shorter than that of patients with invasion to only
      recurrent laryngeal nerve (p = 0.008). CONCLUSIONS: The degree and site of
      invasion is an important prognostic factor for PTC. Our novel classification of
      extrathyroidal invasion is valuable in predicting the prognosis of PTC.

PMID- 22402973
TI  - Two-stage hepatectomy: tape it and hang it, while you can.
AB  - BACKGROUND: Two stage hepatectomy is currently a method of choice for the
      treatment of multifocal bilobar hepatic lesions, especially in the setting of
      hepatic metastases of colorectal malignancies. We describe a technique that
      facilitates second-stage hepatectomy by taping the major vascular structures of
      the right liver and performing a hanging maneuver during the first stage.
      TECHNIQUE: At the first-stage hepatectomy, the right hepatic artery and the right
      portal branch are dissected free and taped with color-coded silicone tapes. A
      classic hanging maneuver is performed using a silicone loop. These three loops
      are left in situ until the second-stage hepatectomy. RESULTS: During the second
      stage hepatectomy, the presence of the vascular tapes appears a major aid in the
      subsequent dissection and control of the major vascular structures, and the
      hanging loop helps parenchymal section and surgeon orientation, without liver
      mobilization. Six patients underwent this procedure. In one patient a biliary
      leak developed after the first-stage procedure, and this required reoperation for
      drainage. Although there is a risk of thrombosis in this setting, there were no
      vascular complications related to the tape positioning, nor was there any
      incidence of infection related to the use of the silicone tape. CONCLUSIONS: The
      technique described here has been in regular use in our department since 2009,
      and in our experience, it may facilitate second-stage hepatectomy.

PMID- 22402974
TI  - Intraperitoneal mesh implantation for fascial dehiscence and open abdomen.
AB  - BACKGROUND: Postoperative fascial dehiscence and open abdomen are severe
      postoperative complications and are associated with surgical site infections,
      fistula, and hernia formation at long-term follow-up. This study was designed to
      investigate whether intraperitoneal implantation of a composite prosthetic mesh
      is feasible and safe. METHODS: A total of 114 patients with postoperative fascial
      dehiscence and open abdomen who had undergone surgery between 2001 and 2009 were
      analyzed retrospectively. Contaminated (wound class 3) or dirty wounds (wound
      class 4) were present in all patients. A polypropylene-based composite mesh was
      implanted intraperitoneally in 51 patients, and in 63 patients the abdominal wall
      was closed without mesh implantation. The primary endpoint was incidence of
      incisional hernia, and the incidence of enterocutaneous fistula was a secondary
      endpoint. RESULTS: The incidence of enterocutaneous fistulas after wound closure
      post-fascial dehiscence (13% vs. 6% without and with mesh, respectively) or post
      open abdomen (22% vs. 28% without and with mesh, respectively) was not
      significantly different. The incidence of incisional hernia was significantly
      lower with mesh implantation compared with no-mesh implantation in both
      contaminated (4% vs. 28%; p = 0.025) and dirty abdominal cavities (5% vs. 34%; p
      = 0.01). CONCLUSIONS: Intra-abdominal contamination is not a contraindication for
      intra-abdominal mesh implantation. The incidence of enterocutaneous fistula is
      not elevated despite the presence of contamination. The rate of incisional
      hernias is significantly reduced after intraperitoneal mesh implantation for
      postoperative fascial dehiscence or open abdomen.

PMID- 22402975
TI  - Randomized controlled trial of visualization versus neuromonitoring of the
      external branch of the superior laryngeal nerve during thyroidectomy.
AB  - BACKGROUND: Injury to the external branch of the superior laryngeal nerve (EBSLN)
      during thyroidectomy results in a lowered fundamental frequency of the voice and
      deteriorated voice performance in producing high-frequency sounds. It remains
      unclear if the use of intraoperative nerve monitoring (IONM) can improve the
      clinical outcome of thyroidectomy in terms of preserved individual voice
      performance. This study was designed to test that hypothesis. METHODS: A total of
      210 consenting female patients planned for total thyroidectomy were randomly
      assigned to two groups equal in size (n = 105): visual inspection of the EBSLN
      and RLN vs. this plus additional EBSLN and RLN monitoring. The primary outcome
      was the identification rate of the EBSLN. The secondary outcomes included:
      anatomical variability of the EBSLN according to the Cernea classification and
      changes in postoperative voice performance. Voice assessment included pre- and
      postoperative videostrobolaryngoscopy and an analysis of maximum phonation time
      (MPT), voice level (VL), fundamental frequency (Fo), and voice quality rating on
      the GRBAS scale. RESULTS: The following differences were found for operations
      without vs. with IONM: identification rate of the EBSLN was 34.3 % vs. 83.8 % (p
      < 0.001), whereas a 10 % or higher decrease in phonation parameters was found in
      10 % vs. 2 % patients for MPT (p = 0.018), 13 % vs. 2 % for VL (p = 0.003), and 9
      % vs. 1 % for Fo (p = 0.03), a change in the GRBAS scale > 4 points in 7 % vs. 1
      % (p = 0.03), and temporary RLN injury was found in 2 % vs. 1 % (p = 0.56),
      respectively. CONCLUSIONS: The use of IONM significantly improved the
      identification rate of the EBSLN during thyroidectomy, as well as reduced the
      risk of early phonation changes after thyroidectomy.

PMID- 22402976
TI  - The distribution of survival times after injury.
AB  - INTRODUCTION: The distribution of survival times after injury has been described
      as "trimodal," but several studies have not confirmed this. The purpose of this
      study was to clarify the distribution of survival times after injury. METHODS: We
      defined survival time (t(s)) as the interval between injury time and declared
      death time. We constructed histograms for t(s) <= 150 min from the 2004-2007
      Fatality Analysis Reporting System (FARS, for traffic crashes) and National
      Violent Death Reporting System (NVDRS, for homicides). We estimated statistical
      models in which death times known only within intervals were treated as interval
      censored. For confirmation, we also obtained EMS response times (t(r)),
      prehospital times (t(p)), and hospital times (t(h)) for decedents in the 2008
      National Trauma Data Bank (NTDB) with t(s) = t(p) + t(h) <= 150. We approximated
      times until circulatory arrest (t(x)) as t(r) for patients pulseless at the
      injury scene, t(p) for other patients pulseless at hospital admission, and t(s)
      for the rest; for any declared t(s), we calculated mean t(x)/t(s). We used this
      ratio to estimate t(x) for hospital deaths in FARS or NVDRS and provide
      independent support for using interval-censored methods. RESULTS: FARS and NVDRS
      deaths were most frequent in the first few minutes. Both showed a second peak at
      35-40 min after injury, corresponding to peaks in hospital deaths. Third peaks
      were not present. Estimated t(x) in FARS and NVDRS did not show second peaks and
      were similar to estimates treating some death times as interval-censored.
      CONCLUSIONS: Increases in frequency of survival times at 35-40 min are primarily
      artifacts created because declaration of death in hospitals is delayed until
      completing resuscitative attempts. By avoiding these artifacts, interval
      censoring methods are useful for analysis of injury survival times.

PMID- 22402979
TI  - Immunology in Serbia: from past to present.

PMID- 22402977
TI  - [Metabolic long-term complications after urinary diversion].
AB  - Metabolic long-term complications and consequences after urinary diversion are
      somewhat neglected. Subclinical metabolic disturbances are quite common; however,
      complications are rare. The absorptive surface of the bowel segment is lost for
      the physiological function of the gastrointestinal tract. Some studies
      demonstrated that at least some of the absorbent and secreting properties of the
      bowel are preserved if exposed to urine. For each bowel segment typical
      complications are reported. Using ileal and/or colon segments, hyperchloremic
      metabolic acidosis may occur. Studies demonstrated that metabolic effects are not
      as severe as suspected and could be prevented if a prophylactic treatment is
      started early.The resection of ileal segments is responsible for malabsorption of
      vitamin B(12) and bile acid; when using colonic segments, electrolyte
      disturbances are more common. Careful patient selection, meticulous follow-up and
      prophylactic treatment are crucial to prevent metabolic complications.

PMID- 22402980
TI  - Family physicians' perceptions and use of electronic clinical decision support
      during the first year of implementation.
AB  - An electronic decision support system (the EBMeDS system) was integrated in one
      of the Electronic Medical Records (EMR) of Belgian family physicians (Feb 2010).
      User acceptance of the system is considered as a necessary condition for the
      effective implementation of any IT project. Facilitators, barriers and issues of
      non-acceptance need to be understood in view of a successful implementation and
      to minimize unexpected adoption behavior. Objectives of the study were the
      assessment of users' perceptions towards the recently implemented EBMeDS system,
      the investigation of user-interactions with the system and possible relationships
      between perceptions and use. A mixed evaluation approach was performed consisting
      of a qualitative and a quantitative analysis. The technology acceptance model of
      UTAUT was used as a structural model for the development of our questionnaire to
      identify factors that may account for acceptance and use of the EBMeDS system
      (seven-point Likert scales). A quantitative analysis of computer-recorded user
      interactions with the system was performed for an evaluation period of 3 months
      to assess the actual use of the system. Qualitative and quantitative analysis
      were linked to each other. Thirty-nine family physicians (12 %) completed the
      survey. The majority of respondents (66 %) had a positive attitude towards the
      system in general. Mean intention to keep using the system was high (5,91 +/-
      1,33). Their perception of the ease of use of the system (mean 5,04 +/- 1,41),
      usefulness (mean 4,69 +/- 1,35) and facilitating conditions (4,43 +/- 1,13) was
      in general positive. Only 0,35 % of reminders were requested on demand, the other
      99,62 % of reminders displayed automatically. Detailed guidelines (long) were
      requested for 0,47 % of reminders automatically shown versus 16,17 % of reminders
      on request. The script behind the reminders was requested for 8,4 % of reminders
      automatically shown versus 13,6 % of reminders on request. The majority of
      respondents demonstrated a relatively high degree of acceptance towards the
      EBMeDS system. Although the majority of respondents was in general positive
      towards the ease of use of the system, usefulness and facilitating conditions,
      part of the statements gave rather mixed results and could be identified as
      important points of interest for future implementation initiatives and system
      improvements. It has to be stressed that our population consisted of a
      convenience sample of early adopters, willing to answer a questionnaire. The
      willingness to adopt the system depends on the willingness to use ICPC coding. As
      such, the quality of reminding partly depends on the quality of coding. There is
      a need to reach a larger population of physicians (including physicians who never
      used the system or stopped using the system) to validate the results of this
      survey.

PMID- 22402981
TI  - Integrin/Fak/Src-mediated regulation of cell survival and anoikis in human
      intestinal epithelial crypt cells: selective engagement and roles of PI3-K
      isoform complexes.
AB  - In human intestinal epithelial crypt (HIEC) cells, the PI3-K/Akt-1 pathway is
      crucial for the promotion of cell survival and suppression of anoikis. Class I
      PI3-K consists of a complex formed by a catalytic (C) and regulatory (R) subunit.
      Three R (p85alpha, beta, and p55gamma) and four C (p110alpha, beta, gamma and
      delta) isoforms are known. Herein, we analyzed the expression of PI3-K isoforms
      in HIEC cells and determined their roles in cell survival, as well as in the
      beta1 integrin/Fak/Src-mediated suppression of anoikis. We report that: (1) the
      predominant PI3-K complexes expressed by HIEC cells are p110alpha/p85beta and
      p110alpha/p55gamma; (2) the inhibition and/or siRNA-mediated expression silencing
      of p110alpha, but not that of p110beta, gamma or delta, results in Akt-1 down
      activation and consequent apoptosis; (3) the expression silencing of p85beta or
      p55gamma, but not that of p85alpha, likewise induces Akt-1 down-activation and
      apoptosis; however, the impact of a loss of p55gamma on both Akt-1 activation and
      cell survival is significantly greater than that from the loss of p85beta; and
      (4) both the p110alpha/p85beta and p110alpha/p55gamma complexes are engaged by
      beta1 integrin/Fak/Src signaling; however, the engagement of p110alpha/p85beta is
      primarily Src-dependent, whereas that of p110alpha/p55gamma is primarily Fak
      dependent (but Src-independent). Hence, HIEC cells selectively express PI3-K
      isoform complexes, translating into distinct roles in Akt-1 activation and cell
      survival, as well as in a selective engagement by Fak and/or Src within the
      context of beta1 integrin/Fak/Src-mediated suppression of anoikis.

PMID- 22402982
TI  - Electronic tools to assist with identification and counseling for overweight
      patients: a randomized controlled trial.
AB  - BACKGROUND: Physicians often do not recognize when their patients are overweight
      and infrequently counsel them about weight loss. OBJECTIVE: To evaluate a set of
      electronic health record (EHR)-embedded tools to assist with identification and
      counseling of overweight patients. DESIGN: Randomized controlled trial.
      PARTICIPANTS: Physicians at an academic general internal medicine clinic were
      randomized to activation of the EHR tools (n = 15) or to usual care (n = 15).
      Patients of these physicians were included in analyses if they had a body mass
      index (BMI) between 27 and 29.9 kg/m(2). INTERVENTION: The EHR tool set included:
      a physician point-of-care alert for overweight (BMI 27-29. 9 kg/m(2)); a
      counseling template to help physicians counsel patients on action plans; and an
      order set to facilitate entry of overweight as a diagnosis and to order relevant
      patient handouts. MAIN MEASURES: Physician documentation of overweight as a
      problem; documentation of weight-specific counseling; physician perceptions of
      the EHR tools; patient self-reported progress toward their goals and perspectives
      about counseling received. KEY RESULTS: Patients of physicians receiving the
      intervention were more likely than those of usual care physicians to receive a
      diagnosis of overweight (22% vs. 7%; p = 0.02) and weight-specific counseling
      (27% vs. 15%; p = 0.02). Most patients receiving counseling in the intervention
      group reported increased motivation to lose weight (90%) and taking steps toward
      their goal (93%). Most intervention physicians agreed that the tool alerted them
      to patients they did not realize were overweight (91%) and improved the
      effectiveness of their counseling (82%); more than half (55%) reported counseling
      overweight patients more frequently (55%). However, most physicians used the tool
      infrequently because of time barriers. CONCLUSIONS: EHR-based alerts and
      management tools increased documentation of overweight and counseling frequency;
      the majority of patients for whom the tools were used reported short-term
      behavior change.

PMID- 22402983
TI  - Clinical outcomes of endoscopic submucosal dissection for early gastric cancer in
      remnant stomach or gastric tube.
AB  - BACKGROUND AND STUDY AIMS: Little information exists regarding the optimal
      treatment of early gastric cancer (EGC) in a remnant stomach or gastric tube. The
      aim of this study was to assess the feasibility and clinical outcomes of
      endoscopic submucosal dissection (ESD) for EGC in a remnant stomach and gastric
      tube. PATIENTS AND METHODS: Between September 2002 and December 2009, ESD was
      performed in 62 lesions in 59 patients with EGC in a remnant stomach (48 lesions)
      or gastric tube (14 lesions). Clinicopathological data were retrieved
      retrospectively to assess the en bloc resection rate, complications, and
      outcomes. Treatment results were assessed according to the indications for
      endoscopic resection, and were compared with those of ESD performed in a whole
      stomach during the same study period. RESULTS: The en bloc resection rates for
      lesions within the standard and expanded indication were 100 % and 93 %,
      respectively. Postoperative bleeding occurred in five patients (8 %). The
      perforation rate was significantly higher (18 %, 11 /62) than that of ESD in a
      whole stomach (5 %, 69 /1479). Among the perforation cases, eight lesions
      involved the anastomotic site or stump line, and ulcerative changes were observed
      in five lesions. The 3-year overall survival rate was 85 %, with eight deaths due
      to other causes and no deaths from gastric cancer. CONCLUSION: A high en bloc
      resection rate was achieved by ESD for EGC in a remnant stomach or gastric tube;
      however, this procedure is still technically demanding due to the high
      complication rate of perforation.

PMID- 22402984
TI  - Standard diagnostic laparoscopy is superior to NOTES approaches: results of a
      blinded, randomized controlled porcine study.
AB  - BACKGROUND AND STUDY AIM: The use of transluminal endoscopic access via the
      stomach or colon for flexible diagnostic peritoneoscopy has been proposed,
      although the diagnostic value of the technique has not yet been fully clarified.
      In this animal trial, the two main natural orifice transluminal endoscopic
      surgery (NOTES) approaches - transgastric (TG) and transcolonic (TC) - were
      compared with standard transabdominal access using both rigid (TAR) and flexible
      instruments (TAF) for diagnostic laparoscopy. METHODS: A total of 48
      peritoneoscopies were performed using two randomly assigned approaches in 24
      anesthetized pigs. The ability of the examinations to detect 576 electrocautery
      markings simulating intraperitoneal metastases, to achieve complete organ
      visualization, and to simulate organ biopsies was analyzed. RESULTS:
      Sensitivities for the detection of lesions were 78.5 %, 59.7 %, 48.6 %, and 38.9
      % for TAR, TAF, TC, and TG, respectively; standard laparoscopy was superior to
      all other approaches (P < 0.01). Among the NOTES approaches, TC was superior for
      examining the upper abdomen (P = 0.03). Complete organ visualization was better
      with the transabdominal approach (visual analogue scale TAR 7.15, TAF 6.71) than
      with the NOTES access routes (TC 5.07, TG 4.35); standard rigid laparoscopy was
      superior to both NOTES approaches (P < 0.01). Organ biopsy simulation was
      possible in 87 %, 85 %, 72 %, and 65 % of cases with TAR, TAF, TC, and TG,
      respectively. Standard rigid laparoscopy was again superior to both NOTES
      approaches (TAR vs. TC, P = 0.03; TAR vs. TG, P < 0.01). CONCLUSIONS: In this
      experimental trial, rigid standard laparoscopy provided better organ
      visualization, better lesion detection, and better biopsy capability than the
      transgastric and transcolonic NOTES approaches. In its current form, NOTES
      appears to be unsuitable for diagnostic laparoscopy.

PMID- 22402986
TI  - Editorial: genetics and democracy.

PMID- 22402985
TI  - Orai1 calcium channels in the vasculature.
AB  - Orai1 was discovered in T cells as a calcium-selective channel that is activated
      by store depletion. Recent studies suggest that it is expressed and functionally
      important also in blood vessels, not only because haematopoietic cells can
      incorporate in the vascular wall but also because Orai1 is expressed and
      functional in vascular smooth muscle cells and endothelial cells. This article
      summarises the arising observations in this new area of vascular research and
      debates underlying issues and challenges for future investigations. The primary
      focus is on vascular smooth muscle cells and endothelial cells. Specific topics
      include Orai1 expression; Orai1 roles in store-operated calcium entry and ionic
      currents of store-depleted cells; blockade of Orai1-related signals by Synta 66
      and other pharmacology; activation or regulation of Orai1-related signals by
      physiological substances and compartments; stromal interaction molecules and the
      relationship of Orai1 to other ion channels, transporters and pumps; transient
      receptor potential canonical channels and their contribution to store-operated
      calcium entry; roles of Orai1 in vascular tone, remodelling, thrombus formation
      and inflammation; and Orai2 and Orai3. Overall, the observations suggest the
      existence of an additional, previously unrecognised, calcium channel of the
      vascular wall that is functionally important particularly in remodelling but
      probably also in certain vasoconstrictor contexts.

PMID- 22402987
TI  - Directional asymmetries and age effects in human self-motion perception.
AB  - Directional asymmetries in vestibular reflexes have aided the diagnosis of
      vestibular lesions; however, potential asymmetries in vestibular perception have
      not been well defined. This investigation sought to measure potential asymmetries
      in human vestibular perception. Vestibular perception thresholds were measured in
      24 healthy human subjects between the ages of 21 and 68 years. Stimuli consisted
      of a single cycle of sinusoidal acceleration in a single direction lasting 1 or 2
      s (1 or 0.5 Hz), delivered in sway (left-right), surge (forward-backward), heave
      (up-down), or yaw rotation. Subject identified self-motion directions were
      analyzed using a forced choice technique, which permitted thresholds to be
      independently determined for each direction. Non-motion stimuli were presented to
      measure possible response bias. A significant directional asymmetry in the
      dynamic response occurred in 27% of conditions tested within subjects, and in at
      least one type of motion in 92% of subjects. Directional asymmetries were usually
      consistent when retested in the same subject but did not occur consistently in
      one direction across the population with the exception of heave at 0.5 Hz.
      Responses during null stimuli presentation suggested that asymmetries were not
      due to biased guessing. Multiple models were applied and compared to determine if
      sensitivities were direction specific. Using Akaike information criterion, it was
      found that the model with direction specific sensitivities better described the
      data in 86% of runs when compared with a model that used the same sensitivity for
      both directions. Mean thresholds for yaw were 1.3+/-0.9 degrees /s at 0.5 Hz and
      0.9+/-0.7 degrees /s at 1 Hz and were independent of age. Thresholds for surge
      and sway were 1.7+/-0.8 cm/s at 0.5 Hz and 0.7+/-0.3 cm/s at 1.0 Hz for subjects
      <50 and were significantly higher in subjects >50 years old. Heave thresholds
      were higher and were independent of age.

PMID- 22402989
TI  - Descriptive epidemiology of type 1 diabetes--is it still in?
AB  - This edition of 'Then and now' discusses the valuable contribution made by Onkamo
      and colleagues to the field of type 1 diabetes epidemiology in their widely cited
      paper 'Worldwide increase in incidence of type I diabetes-the analysis of the
      data on published incidence trends', which was published 13 years ago
      (Diabetologia 1999;42:1395-1403). At the time, this represented the most
      extensive analysis of global trends in the epidemiology of type 1 diabetes, and
      covered/included a considerably larger geographical area than previous studies.
      The data confirmed that there was a worldwide increase in the incidence of
      childhood diabetes during the second half of the 20th century. Predictions made
      by the group for the incidence rates in 2010 pointed to large increases, but in
      retrospect these turned out to be too conservative, particularly among younger
      children. Whether the increase in incidence among children aged <15 years has
      started to level off is unknown. Looking to the future, more data on the
      epidemiology of type 1 diabetes over the whole lifespan are definitely needed. In
      addition, descriptive epidemiology needs to be complemented with 'aetiological'
      epidemiology generating information on the causes of the incidence and prevalence
      trends.

PMID- 22402988
TI  - Adipose tissue and fetal programming.
AB  - Adipose tissue function changes with development. In the newborn, brown adipose
      tissue (BAT) is essential for ensuring effective adaptation to the extrauterine
      environment, and its growth during gestation is largely dependent on glucose
      supply from the mother to the fetus. The amount, location and type of adipose
      tissue deposited can also determine fetal glucose homeostasis. Adipose tissue
      first appears at around mid-gestation. Total adipose mass then increases through
      late gestation, when it comprises a mixture of white and brown adipocytes. BAT
      possesses a unique uncoupling protein, UCP1, which is responsible for the rapid
      generation of large amounts of heat at birth. Then, during postnatal life some,
      but not all, depots are replaced by white fat. This process can be utilised to
      investigate the physiological conversion of brown to white fat, and how it is re
      programmed by nutritional changes in pre- and postnatal environments. A reduction
      in early BAT deposition may perpetuate through the life cycle, thereby
      suppressing energy expenditure and ultimately promoting obesity. Normal fat
      development profiles in the offspring are modified by changes in maternal diet at
      defined stages of pregnancy, ultimately leading to adverse long-term outcomes.
      For example, excess macrophage accumulation and the onset of insulin resistance
      occur in an adipose tissue depot-specific manner in offspring born to mothers fed
      a suboptimal diet from early to mid-gestation. In conclusion, the growth of the
      different fetal adipose tissue depots varies according to maternal diet and, if
      challenged in later life, this can contribute to insulin resistance and impaired
      glucose homeostasis.

PMID- 22402990
TI  - Assessing genetic structure, diversity of bacterial aerosol from aeration system
      in an oxidation ditch wastewater treatment plant by culture methods and bio
      molecular tools.
AB  - Airborne bacteria emissions from oxidation ditch with rotating aeration brushes
      were investigated in a municipal wastewater treatment plant in Beijing, China.
      Microbial samples were collected at different distances from the rotating
      brushes, different heights above the water surface, and different operation state
      over a 3-month period (April, May, and June) in order to estimate the seasonal
      variation and site-related distribution characteristics of the microorganisms
      present. The concentration of bacterial aerosol was analyzed by culture methods,
      while their dominant species, genetic structure and diversity were assayed using
      bio-molecular tools. Results showed that total microbial concentrations were
      highest in June and lowest in April. The mechanical rotation caused remarkable
      variation in concentration and diversity of culturable airborne bacteria before
      and after the rotating brushes. The highest concentration was observed near the
      rotating brushes (931 +/- 129-3,952 +/- 730 CFU/m(3)), with concentration
      decreasing as distance and height increased. Bacterial community polymerase chain
      reaction and denaturing gradient gel electrophoresis indicated that diversity
      decreased gradually with increasing height above the water surface but remained
      relatively constant at the same height. All dominant bacteria identified by DNA
      sequence analysis belonged to Firmicutes. Pathogenic species such as Moraxella
      nonliquefaciens and Flavobacterium odoratum were isolated from the bioaerosols.
      Due to the serious health risks involved, exposure of sewage workers to airborne
      microorganisms caused by brush aerators should be monitored and controlled.

PMID- 22402991
TI  - Distribution of trace metals in marine sediments of the Bay of Palma de Mallorca
      (Mallorca Island, Spain).
AB  - Metals were determined in surface bottom marine sediments of the Bay of Palma de
      Mallorca (Spain) by microwave-assisted acid-oxidant digestion and inductively
      coupled plasma-optical emission spectrometry in order to assess the level and
      distribution of potentially metallic pollutants. Average concentrations found
      were 1.2 +/- 0.3 Al and 1.9 +/- 0.9 Fe (in milligrams per gram), and 8 +/- 2 Cr,
      2 +/- 1 Cu, 60 +/- 10 Mn, 4 +/- 1 Ni, 6 +/- 4 Pb, 50 +/- 7 Sn and 10 +/- 3 Zn (in
      micrograms per gram). Enrichment factors using normalized values to Al were also
      calculated which indicated that sediments were Sn and Pb enriched. Sediments were
      fractionated by grain size: <63, 63-250, 250-500 and >500 (in micrometres), and
      the metals' affinity towards the different fractions was studied. The metals'
      affinity to the finer fraction was evidenced, excluding Sn and Mn that showed
      practically no affinity for fine grains. Latent variables were extracted from the
      data using principal components analysis. It allowed samples to be grouped in two
      clusters, and most of the metals (Al, Cr, Cu, Fe, Ni, Pb and Zn) showed a similar
      distribution pattern. Sn and Mn showed a distinct pattern.

PMID- 22402992
TI  - Determining the most suitable areas for artificial groundwater recharge via an
      integrated PROMETHEE II-AHP method in GIS environment (case study: Garabaygan
      Basin, Iran).
AB  - Flood spreading is a suitable strategy for controlling and benefiting from
      floods. Selecting suitable areas for flood spreading and directing the floodwater
      into permeable formations are amongst the most effective strategies in flood
      spreading projects. Having combined geographic information systems (GIS) and
      multi-criteria decision analysis approaches, the present study sought to locate
      the most suitable areas for flood spreading operation in the Garabaygan Basin of
      Iran. To this end, the data layers relating to the eight effective factors were
      prepared in GIS environment. This stage was followed by elimination of the
      exclusionary areas for flood spreading while determining the potentially suitable
      ones. Having closely examined the potentially suitable areas using the Preference
      Ranking Organization Method for Enrichment Evaluations (PROMETHEE) II and
      analytic hierarchy process (AHP) methods, the land suitability map for flood
      spreading was produced. The PROMETHEE II and AHP were used for ranking all the
      alternatives and weighting the criteria involved, respectively. The results of
      the study showed that most suitable areas for the artificial groundwater recharge
      are located in Quaternary Q(g) and Q(gsc) geologic units and in geomorphological
      units of pediment and Alluvial fans with slopes not exceeding 3%. Furthermore,
      significant correspondence between the produced map and the control areas, where
      the flood spreading projects were successfully performed, provided further
      evidence for the acceptable efficiency of the integrated PROMETHEE II-AHP method
      in locating suitable flood spreading areas.

PMID- 22402993
TI  - In vivo microRNA detection and quantitation in cerebrospinal fluid.
AB  - Alterations in microRNA (miRNA) expression in postmortem brain tissue or
      peripheral blood have been linked to schizophrenia. Cerebrospinal fluid might
      provide an in vivo biomarker more directly reflecting functional changes in the
      brain. The goals of this study were to determine the feasibility of detecting
      miRNAs in cerebrospinal fluid and to compare miRNA levels in cerebrospinal fluid
      versus blood. Four healthy volunteers and four patients with psychotic disorders
      underwent a lumbar puncture and a blood draw. Expression of 378 validated miRNAs
      was assessed from each biofluid type for each subject using microarray
      technology. Five miRNAs were chosen for validation with quantitative polymerase
      chain reaction. A substantial number of miRNAs (n = 95) were exclusively or
      predominately detected in cerebrospinal fluid (CSF). Levels of 35 miRNAs detected
      in both CSF and blood samples in all subjects were poorly correlated. The
      investigation of miRNAs in CSF can help advance the understanding of psychiatric
      diseases and particularly schizophrenia.

PMID- 22402995
TI  - Gender and visibility of sexual cues influence eye movements while viewing faces
      and bodies.
AB  - Faces and bodies convey important information for the identification of potential
      sexual partners, yet clothing typically covers many of the bodily cues relevant
      for mating and reproduction. In this eye tracking study, we assessed how men and
      women viewed nude and clothed, same and opposite gender human figures. We found
      that participants inspected the nude bodies more thoroughly. First fixations
      landed almost always on the face, but were subsequently followed by viewing of
      the chest and pelvic regions. When viewing nude images, fixations were biased
      away from the face towards the chest and pelvic regions. Fixating these regions
      was also associated with elevated physiological arousal. Overall, men spent more
      time looking at female than male stimuli, whereas women looked equally long at
      male and female stimuli. In comparison to women, men spent relatively more time
      looking at the chests of nude female stimuli whereas women spent more time
      looking at the pelvic/genital region of male stimuli. We propose that the
      augmented and gender-contingent visual scanning of nude bodies reflects selective
      engagement of the visual attention circuits upon perception of signals relevant
      to choosing a sexual partner, which supports mating and reproduction.

PMID- 22402994
TI  - Obstructive sleep apnea severity correlates with cellular and plasma oxidative
      stress parameters and affective symptoms.
AB  - Obstructive sleep apnea syndrome (OSAS) is considered a sleep-related respiratory
      disorder, characterized by repetitive episodes of complete (apnea) or partial
      (hypopnea) obstruction of airflow in the upper airway (UA) during sleep. The
      pathophysiology of upper airway obstruction in OSAS is multifactorial, leading to
      a chronic recurrent state of intermittent hypoxemia and reoxygenation during
      sleep, maintaining a state of oxidative stress, which seems to be the key to the
      pathophysiological manifestations of OSAS, and is associated with the development
      of a number of high morbidity-mortality systematic complications, such as
      obesity, type 2 diabetes, metabolic syndrome, and cardiovascular and
      neuropsychological diseases. This study is an open, cross-sectional, and
      comparative clinical trial, whose general objective was to assess the correlation
      between OSAS severity, oxidative stress markers, and the presence of affective
      symptoms (depressive and anxious) in OSAS patients. We studied 38 adult males,
      who had been diagnosed with OSAS by overnight polysomnography, between 18 and 60
      years of age, divided into three groups: group 1-10 individuals with mild OSAS
      (AHI between 5 and 14.9/h), group 2-13 individuals with moderate OSAS (AHI
      between 15 and 30/h), and group 3-15 individuals with severe OSAS (AHI >30/h).
      All individuals were evaluated for level of subjective sleepiness using the
      Epworth Sleepiness Scale, for depressive and anxiety symptoms by the Hamilton
      Depression (HAM-D) and Anxiety (HAM-A) Scales, and for parameters of the
      oxidative stress state, measuring superoxide radical and serum nitrates and
      nitrites levels. There was a progressive and significant increase in the state of
      oxidative stress (p < 0.05), in the total score of depressive symptoms (p =
      0.001) and in the overall score of anxiety symptoms (p = 0.004) directly
      proportional to the severity of apnea when comparing the mild group to the severe
      group. Positive correlations were identified between superoxide production and
      the apnea-hypopnea index (AHI) (r = 0.48), Epworth sleepiness score (r = 0.36),
      and Hamilton depression score (HAM-D) (r = 0.40); between serum nitrates and
      nitrites levels and SO(2) min (r = 0.44); and between the AHI and the HAM-D (r =
      0.51) score and HAM-A (r = 0.40) score. Negative correlations were observed
      between the AHI and serum nitrates and nitrites levels (r = -0.42), between
      superoxide production and SO(2) min (r = -0.31), between serum nitrates and
      nitrites levels and HAM-D (r = -0.50) and HAM-A (-0.42) scores, and between SO(2)
      min and HAM-D (r = -0.48) and HAM-A (r = -0.40) scores. According to the results
      of this study, we can conclude that (1) individuals with OSAS show an increase in
      the production of superoxide radical and a decrease in serum nitrates and
      nitrites levels, which are objective signs of a state of oxidative stress. (2)
      The more severe the OSAS, the more fragmented the sleep and the greater the
      nocturnal hypoxemia, the more severe is the oxidative stress state and the
      greater is the incidence of daytime symptoms, especially sleepiness and
      depressive and anxiety symptoms. Future studies might explore the investigation
      of oxidative stress parameters as an alternative approach to anticipate symptoms,
      measure prognosis, and monitor OSAS progression or treatment response.

PMID- 22402996
TI  - Who, what, where, when (and maybe even why)? How the experience of sexual reward
      connects sexual desire, preference, and performance.
AB  - Although sexual behavior is controlled by hormonal and neurochemical actions in
      the brain, sexual experience induces a degree of plasticity that allows animals
      to form instrumental and Pavlovian associations that predict sexual outcomes,
      thereby directing the strength of sexual responding. This review describes how
      experience with sexual reward strengthens the development of sexual behavior and
      induces sexually-conditioned place and partner preferences in rats. In both male
      and female rats, early sexual experience with partners scented with a neutral or
      even noxious odor induces a preference for scented partners in subsequent choice
      tests. Those preferences can also be induced by injections of morphine or
      oxytocin paired with a male rat's first exposure to scented females, indicating
      that pharmacological activation of opioid or oxytocin receptors can "stand in"
      for the sexual reward-related neurochemical processes normally activated by
      sexual stimulation. Conversely, conditioned place or partner preferences can be
      blocked by the opioid receptor antagonist naloxone. A somatosensory cue (a rodent
      jacket) paired with sexual reward comes to elicit sexual arousal in male rats,
      such that paired rats with the jacket off show dramatic copulatory deficits. We
      propose that endogenous opioid activation forms the basis of sexual reward, which
      also sensitizes hypothalamic and mesolimbic dopamine systems in the presence of
      cues that predict sexual reward. Those systems act to focus attention on, and
      activate goal-directed behavior toward, reward-related stimuli. Thus, a critical
      period exists during an individual's early sexual experience that creates a "love
      map" or Gestalt of features, movements, feelings, and interpersonal interactions
      associated with sexual reward.

PMID- 22402997
TI  - Characterizing the self-system over time in adolescence: internal structure and
      associations with internalizing symptoms.
AB  - The longitudinal effects among self and identity processes, and between these
      processes and internalizing symptoms, are not well understood. As a result, the
      present study was designed to ascertain the over-time effects among identity
      commitment, reconsideration of commitments, and self-concept clarity, as well as
      to map the interplay of these self and identity processes with anxiety and
      depressive symptoms in early adolescence. A sample of 923 Dutch adolescents (mean
      age 12.4 years at Time 1; 49.3% female) participated at each of five annual
      assessments. Multivariate growth curve and cross-lagged panel models indicated
      that the association between self-concept clarity and commitment was
      bidirectional, that reconsideration occurs based on problems or dissatisfaction
      with self-concept clarity and with identity commitments, and that self-concept
      clarity (but not commitment or reconsideration) temporally precedes depressive
      and anxiety symptoms. Results are discussed in terms of the structure of the self
      system and its associations with internalizing symptoms.

PMID- 22402998
TI  - [Subjective and objective hearing test results for children with orofacial
      clefts].
AB  - OBJECTIVE: The hearing status of children with orofacial clefts was analysed
      using objective hearing tests over an average of 38.7 months following soft
      palate closure. We investigated the influence of: timing of closure, type of
      cleft, importance of grommets insertion and concomitant craniofacial syndromes
      such as Pierre Robin (PRS). MATERIAL AND METHODS: 70 children were selected for
      prospective audiometric testing twice yearly. RESULTS: The average age at
      surgical closure was 8.3 months. More than half had PRS, but their hearing levels
      were not significantly different from those who did not. Neither did cleft type
      or timing of closure seem to have any influence. The portion of children with a
      hearing level better than 30 dB increased after repair from 38.6% to 81.4%-
      significant at 0.001 and remained stable more than 24 months later. In the group
      of children with concomitant grommets insertion, it was also found that also more
      than 80% achieved longstanding normal hearing. CONCLUSIONS: There is no long
      lasting hearing loss which has any relevance to speech. The only intervention of
      any consequence is insertion of pressure equalising/tympanostomy tubes (grommets)
      in cases of primary palatal clefts when hearing is substantially impaired at the
      time of soft palate closure.

PMID- 22402999
TI  - [Endoscopic frontal sinus revision following transcutaneous endoscopic puncture
      and diaphanoscopy].
AB  - BACKGROUND: Endoscopic revision sinus surgery in case of frontal sinus pyocele
      may poses a great surgical challenge for various reasons. Due to the often
      troublesome anatomical changes caused by prior resection and findings of scaring
      with new bone formation, the identification of the frontal sinus in revision
      surgery is frequently a challenge for the surgeon. An easy endoscopic technique
      for a safe endonasal identification of the frontal sinus in revision surgery is
      therefore of major importance. MATERIAL AND METHODS: 4 patients (3 men, 1 female)
      were enrolled with an acute frontal pyocele following prior open frontal sinus
      surgery over an external access. All patients were subjected to standard
      endonasal endoscopic frontal sinus surgery. The frontal sinus was endonasally
      approached after endoscopic transcutaneous frontal sinus puncture through the pre
      existing bone defect achieving a diaphanoscopy with endonasal identification of
      the frontal sinus floor. RESULTS: The external endoscopic puncture and
      illumination of the frontal sinus was performed in all 4 patients with a modular
      endoscopic system (Sinus View). A visual exploration of the frontal sinus was
      easily carried out after irrigation. A clear endonasal identification of the
      frontal sinus floor by diaphanoscopy was achieved in all patients and guided a
      direct opening of the frontal sinus. A stable frontal sinus drainage type IIb
      according to Draf was reached in all cases. CONCLUSION: Transcutaneous frontal
      sinus puncture with an modular endoscope allows not only to verify frontal sinus
      pyocele diagnosis, but also provides the option to open the frontal sinus
      directly guided by the diaphanoscopy at the frontal sinus floor even in
      situations of complex anatomy.

PMID- 22403000
TI  - Pre- and postoperative nutritional deficiencies in obese patients undergoing
      laparoscopic sleeve gastrectomy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has been identified as an
      innovative surgical approach for the treatment of obesity and is increasingly
      applied worldwide. However, data on outcome of LSG regarding nutrient
      deficiencies, protein status, and body composition are scarce. METHODS: Obese
      subjects (54; f:m = 4:1) scheduled for LSG were included in this study.
      Micronutrient analysis, protein status assessment, and bioimpedance measures were
      performed before and 1, 3, 6, and 12 months after LSG. RESULTS: In 51% of the
      subjects, at least one micronutrient deficiency was found prior to surgery.
      Baseline concentrations were below normal for 25-OH vitamin D (27%), iron (29%),
      vitamin B6 (11%), vitamin B12 (9%), folate (6%), and potassium (7%). Frequencies
      of deficiencies for vitamin B12, folate, iron, and vitamin B6 tended to increase
      following LSG within the first year after intervention. Also, parameters of
      protein status (albumin, transferrin, cholinesterase, and total protein)
      decreased. After surgery, bioimpedance measures indicated a reduction of total
      body fat, but also of body cell mass. CONCLUSIONS: Preoperative micronutrient
      deficiencies were common in morbid obese individuals scheduled for LSG. LSG had a
      modest effect on micronutrient status by further reducing iron, vitamin B12,
      vitamin B6, and folate within the first year after intervention. Our data suggest
      that especially obese patients with preoperative deficits require control and
      supplementation of micronutrients and protein in the postoperative period.

PMID- 22403001
TI  - Personalized medicine: challenge and promise.
AB  - The new health care buzz words include "personalized or individualized medicine."
      Populations such as American Indians and Alaska Natives potentially have much to
      gain from this new science to overcome the known health disparities in these
      populations. This will require participation and acceptance of diverse
      populations. This article reviews the promise and challenges of individualizing
      cancer care using principles of community-based participatory research.

PMID- 22403002
TI  - PDGFRbeta expression in tumor stroma of pancreatic adenocarcinoma as a reliable
      prognostic marker.
AB  - Pancreatic adenocarcinoma is a lethal disease that often develops a desmoplastic
      reaction in tumor stroma. In general, desmoplasia is thought to promote tumor
      growth. However, its molecular pathology and prognostic potential have not been
      fully investigated. Here, we investigate 26 cases of pancreatic ductal
      adenocarcinoma and examine the clinicopathological association between survival
      and expression levels of several molecular markers for stromal cells. These
      include alpha-smooth muscle actin (SMA) and platelet-derived growth factor (PDGF)
      receptor beta (PDGFRbeta). Both are markers of activated fibroblasts or
      pancreatic stellate cells (PSCs) that play an important role in desmoplasia. The
      staining patterns of both molecular markers were not uniform, so we categorized
      them into 3 grades (high, middle, and low) according to intensity. Interestingly,
      Kaplan-Meier analysis revealed that higher expression of PDGFRbeta matched
      shorter prognosis (p=0.0287, log-rank test) as well as lymphatic invasion and
      lymph node metastasis, whereas SMA did not (p=0.6122). Our results suggest the
      prognostic potential of cancer stroma via PDGF-B signaling. Regulation of PDGF-B
      associated signaling crosstalk between cancer cells and stroma cells, therefore,
      may indicate a possible therapeutic target for desmoplastic malignant tumors such
      as pancreatic adenocarcinoma.

PMID- 22403003
TI  - Serum concentrations and clinical significance of soluble CD40 ligand in patients
      with multiple myeloma.
AB  - Multiple myeloma (MM) is a disease of plasma cells that express the CD40
      receptor. Binding of the CD40 by its natural ligand, CD40 ligand (CD40L),
      produces growth arrest and/or apoptosis in MM. To evaluate serum levels of
      soluble CD40L (sCD40L) in MM patients and to correlate them with markers of
      disease activity and angiogenesis, such as vascular endothelial growth factor
      (VEGF), hepatocyte growth factor (HGF), interleukin-6 (IL-6), proliferation
      marker Ki-67 proliferation index (Ki-67 PI) and bone marrow plasma cell
      infiltration, fifty-eight MM patients were studied in diagnosis and 43 of them
      after completion of treatment. Serum levels of sCD40L, VEGF, HGF and IL-6 were
      measured by ELISA, whereas Ki-67 PI and bone marrow plasma cell infiltration were
      measured by immunohistochemistry. Pre-treatment levels of sCD40L in MM patients
      were higher compared to controls and to their levels after effective treatment.
      Treatment regimen did not affect the degree of reduction of sCD40L levels,
      whereas patient in partial remission had increased levels compared to those with
      better response. Significant differences were found among disease stages. There
      were also positive correlations between CD40L with HGF, VEGF, IL-6 and Ki-67 PI.
      Elevated serum sCD40L is found in patients with advanced MM stage and can be
      reduced after effective treatment. Increased levels of this mediator are
      correlated with angiogenic cytokines, providing evidences that CD40L/CD40
      interactions play a significant role in the mechanisms of angiogenesis in MM
      patients.

PMID- 22403004
TI  - Improved RAPD-PCR for discriminating breeds of water buffalo.

PMID- 22403005
TI  - Crystal structures of putative phosphoglycerate kinases from B. anthracis and C.
      jejuni.
AB  - Phosphoglycerate kinase (PGK) is indispensable during glycolysis for anaerobic
      glucose degradation and energy generation. Here we present comprehensive
      structure analysis of two putative PGKs from Bacillus anthracis str. Sterne and
      Campylobacter jejuni in the context of their structural homologs. They are the
      first PGKs from pathogenic bacteria reported in the Protein Data Bank. The
      crystal structure of PGK from Bacillus anthracis str. Sterne (BaPGK) has been
      determined at 1.68 A while the structure of PGK from Campylobacter jejuni (CjPGK)
      has been determined at 2.14 A resolution. The proteins' monomers are composed of
      two domains, each containing a Rossmann fold, hinged together by a helix which
      can be used to adjust the relative position between two domains. It is also shown
      that apo-forms of both BaPGK and CjPGK adopt open conformations as compared to
      the substrate and ATP bound forms of PGK from other species.

PMID- 22403006
TI  - Generalization of a model based on biophysical concepts of muscle activation,
      fatigue and recovery that explains exercise performance.
AB  - To address the limitations of regression-based performance models, the literature
      describes a fatigue model that reduces the complexities of motor unit activation
      into a set of first-order differential equations requiring only a few parameters
      to capture the global effects of activation physiology (M0: maximal force
      generating capacity, F: fatigue rate, R: recovery rate). However, there are no
      solutions to the general form of the equations, which limits its applicability.
      We formulate an algorithm that allows the equations to be solved if an arbitrary
      force profile is specified. Furthermore, we support the validity of the model,
      applying it to exercises found in the literature including quadriceps
      contractions (M0=954+/-326 N, F=2.5+/-0.4%.s(-1), R=0.3+/-0.3%.s(-1)), cycling
      (M0=1095+/-486 W, F=3.5+/-0.3%.s(-1), R=1.1+/-0.3%.s(-1)) and running (M0=9.2+/
      1.2 m.s(-1), F=0.9+/-0.4%.s(-1), R=1.0+/-0.3%.s(-1)), where effective muscle
      forces are converted to cycling power and running speed. The model predicts
      muscle output for 10 maximum efforts and 32 endurance tests, where the
      coefficient of determination (R2) ranged from 0.81 to 1.00. These results support
      the hypothesis found in the literature that motor unit activation and fatigue
      mechanisms lead to a cumulative muscle fatigue effect that can be observed in
      exercise performance.

PMID- 22403007
TI  - Myostatin is associated with age-related human muscle stem cell dysfunction.
AB  - Human aging is accompanied by a progressive loss of muscle mass (sarcopenia). We
      tested the hypothesis that older males (OMs, 70+/-4 yr, n=9) would have a blunted
      myogenic response to a physiological stimulus compared to younger controls (21+/
      3 yr, n=9). Subjects completed an acute bout of intense unilateral muscle
      loading. Young healthy males matched for body mass and activity level served as
      the control group. Muscle biopsies and blood were obtained before and at 3, 24,
      and 48 h after muscle loading. The muscle stem cell response was analyzed using
      flow cytometry, immunofluorescent microscopy, and standard protein and mRNA
      analysis. OMs had 35% fewer basal stem cells and a type II fiber-specific
      impairment in stem cell content and proliferation. Myogenic determination factor
      staining and cell cycle analysis illustrated a severely blunted progression
      through the myogenic program. Myostatin protein and mRNA were 2-fold higher in
      OMs. Stem cell-specific myostatin levels were not different at baseline; however,
      there were 67% more myostatin-positive type II-associated stem cells in OMs at 24
      h. These data illustrate an age-related impairment of stem cell function in a
      fiber type-specific manner. The greater colocalization of myostatin with stem
      cells provides a mechanism for the impaired myogenic capacity of aged muscle.

PMID- 22403008
TI  - The E2F6 repressor activates gene expression in myocardium resulting in dilated
      cardiomyopathy.
AB  - The E2F/Rb pathway regulates cardiac growth and development and holds great
      potential as a therapeutic target. The E2F6 repressor is a unique E2F member that
      acts independently of pocket proteins. Forced expression of E2F6 in mouse
      myocardium induced heart failure and mortality, with severity of symptoms
      correlating to E2F6 levels. Echocardiography demonstrated a 37% increase (P<0.05)
      in left ventricular end-diastolic diameter and reduced ejection fraction (<40%,
      P<0.05) in young transgenic (Tg) mice. Microarray and qPCR analysis revealed a
      paradoxical increase in E2F-responsive genes, which regulate the cell cycle,
      without changes in cardiomyocyte cell number or size in Tg mice. Young adult Tg
      mice displayed a 75% (P<0.01) decrease in gap junction protein connexin-43,
      resulting in abnormal electrocardiogram including a 24% (P<0.05) increase in PR
      interval. Further, mir-206, which targets connexin-43, was up-regulated 10-fold
      (P<0.05) in Tg myocardium. The mitogen-activated protein kinase pathway, which
      regulates the levels of miR-206 and connexin-43, was activated in Tg hearts.
      Thus, deregulated E2F6 levels evoked abnormal gene expression at transcriptional
      and post-transcriptional levels, leading to cardiac remodeling and dilated
      cardiomyopathy. The data highlight an unprecedented role for the strict
      regulation of the E2F pathway in normal postnatal cardiac function.

PMID- 22403009
TI  - Genetic variation and association mapping of silica concentration in rice hulls
      using a germplasm collection.
AB  - An association analysis on the genetic variability for silica concentration in
      rice hulls was performed using a "Mini-Core" set of 174 accessions representative
      of the germplasm diversity found in the USDA world collection of rice. Hull
      silica concentration was determined in replicated trials conducted in two
      southern states in the USA and was analyzed for its association with 164 genome
      wide DNA markers. Among the accessions, the average silica concentration ranged
      from 120 to 251 mg g(-1). Ample variation was seen within each of the five sub
      populations of rice, as well as the 14 geographic regions that the accessions
      originated from. There was also an effect due to location and accession *
      location (G * E) interaction demonstrating the importance of assessing silica
      concentration across multiple environments. Twelve markers on ten chromosomes
      were significantly associated with hull silica concentration. Six markers
      (RM5644, RM5371, RM1335, RM283, RM263, and RM178) corroborated quantitative trait
      locus for silica concentration identified in other mapping studies. Our results
      provide germplasm and genetic markers that will assist breeding efforts to
      develop cultivars that have either high or low hull silica concentration. High
      silica hulls are good raw material for silica based industrial compounds, while
      low silica hulls are more biodegradable.

PMID- 22403010
TI  - A predictable worm: application of Caenorhabditis elegans for mechanistic
      investigation of movement disorders.
AB  - Ongoing investigations into causes and cures for human movement disorders are
      important toward the elucidation of diseases such as Parkinson's disease (PD) and
      dystonia. The use of animal model systems can provide links to susceptibility
      factors, as well as therapeutic interventions. In this regard, the nematode
      roundworm, Caenorhabditis elegans, is ideal for examining age-dependent
      neurodegenerative disease studies. It is genetically tractable, has a short
      lifespan, and a well-defined nervous system. Green fluorescent protein is readily
      visualized in C. elegans because it is a transparent organism, thus the nervous
      system and factors that alter the viability of neurons can be directly examined
      in vivo. Through expression of the human PD-associated protein (alpha-synuclein
      in the worm dopamine neurons), neurodegeneration is observed in an age-dependent
      manner. Furthermore, expression of the early-onset dystonia-related protein
      torsinA increases vulnerability to endoplasmic reticulum (ER) stress in C.
      elegans, because torsinA is located in the ER. Here we provide an overview of
      collaborative studies we have conducted that collectively demonstrate the
      usefulness of the nematode model to discern functional effectors of dopaminergic
      neurodegeneration and ER stress that translate to mammalian data in the fields of
      PD and dystonia. Taken together, the application of C. elegans toward the
      evaluation of genetic modifiers for movement disorders research has predictive
      value and serves to accelerate the path forward for therapeutic interventions.

PMID- 22403011
TI  - Delineation of the molecular mechanism for disulfide stress-induced aluminium
      toxicity.
AB  - Following our previous finding that the sulfhydryl-oxidising chemical diamide
      induced a marked elevation of cellular Al(3+) (Wu et al., Int J Mol Sci, 12:8119
      8132, 2011), a further investigation into the underlying molecular mechanism was
      carried out, using the eukaryotic model organism Saccharomyces cerevisiae. The
      effects of non-toxic dose of diamide (0.8 mM) and a mild dose of aluminium
      sulphate (Al(3+)) (0.4 mM) were determined prior to the screening of gene
      deletion mutants. A total of 81 deletion mutants were selected for this study
      according to the available screening data against Al(3+) only (Kakimoto et al.,
      BioMetals, 18: 467-474, 2005) and diamide only (Thorpe et al., Proc Natl Acad Sci
      USA, 101: 6564-6569, 2004). On the basis of our screening data and the cluster
      analysis, a cluster containing the gene deletions (rpe1?, sec72?, pdr5? and
      ric1?) was found to be specifically sensitive to the mixture of diamide and
      Al(3+). However gnp1?, mch5? and ccc1? mutants were resistant. Dithiothreitol
      (DTT) and ascorbate markedly reversed the diamide-induced Al(3+) toxicity.
      Inductively-coupled plasma optical emission spectrometry demonstrated that DTT
      reduced the intracellular Al(3+) content in diamide/Al(3+)-treated yeast cells
      six-fold compared to the non-DTT controls. These data together revealed that the
      pleiotropic drug resistance transporter (Pdr5p) and vacuolar/vesicular transport
      related proteins (Ric1p and Sec72p) are the targets of diamide. A dysfunctional
      membrane-bound Pdr5p terminates the detoxification pathway for Al(3+) at the
      final step, leading to intracellular Al(3+) accumulation and hence toxicity. As
      Al(3+) toxicity has been a problem in agriculture and human health, this study
      has provided a significant step forward in understanding Al(3+) toxicity.

PMID- 22403012
TI  - Comparing DNA extraction methods for analysis of botanical materials found in
      anti-diabetic supplements.
AB  - A comparative performance evaluation of DNA extraction methods from anti-diabetic
      botanical supplements using various commercial kits was conducted, to determine
      which produces the best quality DNA suitable for PCR amplification, sequencing
      and species identification. All plant materials involved were of suboptimal
      quality showing various levels of degradation and therefore representing real
      conditions for testing herbal supplements. Eight different DNA extraction methods
      were used to isolate genomic DNA from 13 medicinal plant products. Two methods
      for evaluation, DNA concentration measurements that included absorbance ratios as
      well as PCR amplifiability, were used to determine quantity and quality of
      extracted DNA. We found that neither DNA concentrations nor commonly used UV
      absorbance ratio measurements at A(260)/A(280) between 1.7 and 1.9 are suitable
      for globally predicting PCR success in these plant samples, and that PCR
      amplifiablity itself was the best indicator of extracted product quality.
      However, our results suggest that A(260)/A(280) ratios below about 1.3 and above
      2.3 indicated a DNA quality too poor to amplify. Therefore, A(260)/A(280)
      measurements are not useful to identify samples that likely will amplify but can
      be used to exclude samples that likely will not amplify reducing the cost for
      unnecessarily subjecting samples to PCR. The two Nucleospin((r)) plant II kit
      extraction methods produced the most pure and amplifiable genomic DNA extracts.
      Our results suggest that there are clear, discernable differences between
      extraction methods for low quality plant samples in terms of producing
      contamination-free, high-quality genomic DNA to be used for further analysis.

PMID- 22403013
TI  - Morphology and mechanics of chondroid cells from human adipose-derived Stem cells
      detected by atomic force microscopy.
AB  - Chondroid cell from human adipose-derived stem cells (ADSCs) has emerged as an
      alternative treatment option for articular cartilage defects. Herein, we
      successfully compared ADSCs, normal chondrocytes, and chondroid cells. The
      comparative study of ADSCs and chondroid cells revealed type II collagen (COL II)
      and glycosaminoglycans expression of chondroid cells were similar to those in
      normal chondrocytes, and much higher than ADSCs. Using atomic force microscope
      (AFM) and laser confocal scanning microscopy (LCSM), we compared the differences
      in morphology, mechanical properties, and F-actin distribution between chondroid
      cells and normal chondrocytes. Our results showed no differences observed between
      these two types of cells regarding morphology, stiffness, and F-actin
      distribution. However, found that the adhesion force in chondroid cells was lower
      than that in normal chondrocytes. Taken together, our AFM and LCSM analyses
      suggest that the lower adhesion force in chondroid cells may contribute to the
      dedifferentiation of ADSC-derived chondroid cells. Future examination of surface
      adhesion force-related protein expression will likely provide new insight into
      the molecular mechanisms underlying the dedifferentiation of ADSC-derived
      chondroid cells.

PMID- 22403014
TI  - [Medical care unit -- a suitable instrument for ambulatory patient-adequate care
      and performance-related remuneration].
AB  - BACKGROUND: The question of whether a medical care unit is an appropriate tool
      for outpatient care has been discussed for a long time. Our aim is to investigate
      whether the MCU is an effective instrument for outpatient care and adequate
      performance-related remuneration. MATERIAL AND METHODS: This retro- and
      prospective overview of the work included statements on legal foundations for
      medical care units, for reimbursement of services in medical care units, the
      development of medical care centres in Germany and a listing of the specific
      advantages and disadvantages of an MCU. This article focuses on the generally
      applicable facts and complements them with examples from general, visceral and
      vascular surgery. The main quantitative data on medical centre statistics come
      from different publications of the National Association of Statutory Health
      Insurance for Physicians. RESULTS: From a legal point of view the instrument MCU
      allows the participating of ambulatory and stationary care in the framework of
      medical care contracts. This has been especially extended for stationary
      applications, including the spectrum of possibilities that can contribute under
      certain circumstances for the provision of medical care in underdeveloped
      regions. Freelancers can benefit primarily from financial risk and minimising
      bureaucratic routine. The remuneration for services performed in the MCU is
      analogous to that of other ambulatory care providers. Basically, there are no
      disadvantages, but a greater design freedom and opportunities for the generation
      of aggregates are visible. The number of MCU in Germany has quadrupled in the
      last five years, indicating an establishment of an outpatient care landscape. MCU
      offers from the patient's perspective, providers and policy specific advantages
      and disadvantages. Indeed the benefits outweigh the disadvantages, but this is
      not yet verified by qualitative studies. CONCLUSION: The question of the
      appropriateness of medical care units as outpatient care instrumentation must be
      considered differentially. Under current conditions it appears suitable for
      ensuring the MCU and the supplement of care supply. Whether a value can be
      generated in the quality of care of patients, however, has to be examined
      separately, as there are no valid data so far. The same applies to economic
      assessments of costs and benefits from an economic perspective.

PMID- 22403015
TI  - The clinical implementation of whole genome sequencing: a conversation with seven
      scientific experts.
AB  - This commentary is based on the key note address given by Jordan Lerner-Ellis at
      the annual symposium of the Society for the Study of Inborn Errors of Metabolism,
      held in Geneva, Switzerland in August 2011. The content of the address was
      developed from a series of discussions with seven clinicians and medical
      geneticists, all having a long-time interest in genetic testing and genomic
      medicine (the interviews were not intended to be a forum for the introduction of
      new data). All participants were asked to offer their views on five questions:
      the benefits of using whole genome sequencing (WGS) in the clinic; the
      corresponding risks; the limitations on its wider use; the interviewees'
      particular interests in using WGS in their practice; and projected timelines for
      successful adoption in clinical medicine.

PMID- 22403016
TI  - Clinical features and heteroplasmy in blood, urine and saliva in 34 Dutch
      families carrying the m.3243A > G mutation.
AB  - The m.3243A>G mutation has become known as the MELAS mutation. However, many
      other clinical phenotypes associated with this mutation have been described,most
      frequently being Maternally Inherited Diabetes and Deafness (MIDD). The m.3243A>G
      mutation, can be detected in virtually all tissues, however heteroplasmy differs
      between samples. Recent reports indicate, a preference to perform mutation
      analysis in Urinary Epithelial Cells(UEC). To test this, and to study a
      correlation between the mutational load in different tissues with two
      mitochondrial scoring systems (NMDAS and NPMDS) we investigated 34 families
      carrying the m.3243A>G mutation. Heteroplasmy was determined in three non
      invasively collected samples,namely leucocytes, UEC and buccal mucosa. We
      included 127 patients, of which 82 carried the m.3243A>G mutation.None of the
      children (n011) had specific complaints. In adults(n071), a median NMDAS score of
      15 (IQR 10-24) was found. The most prevalent symptoms were hearing loss(68 %),
      gastro-intestinal problems (59 %), exercise intolerance(54 %) and glucose
      intolerance (52 %). Ten patients had neurologic involvement. Buccal mucosa had
      the best correlation with the NMDAS in all adults (r00.437, p<0.001),whereas UEC
      had the strongest correlation with the NMDAS in severely affected patients
      (r00.593, p00.002). Heteroplasmy declined significantly with increasing age in
      all three samples (leucocytes r0-0.705 (p<0.001), UEC r0-0.374 (p00.001), buccal
      mucosa r0-0.460 (p<0.001). In our cohort of 82 patients, the m.3243A>Gmutation
      causes a wide variety of signs and symptoms, MIDD being far more prevalent than
      MELAS. Looking at the characteristics of the three noninvasively available
      tissues for testing heteroplasmy we confirm that UEC are the preferred sample to
      test [corrected].

PMID- 22403017
TI  - Urinary AASA excretion is elevated in patients with molybdenum cofactor
      deficiency and isolated sulphite oxidase deficiency.
AB  - Analysis of alpha-aminoadipic semialdehyde is an important tool in the diagnosis
      of antiquitin deficiency (pyridoxine-dependent epilepsy). However continuing use
      of this test has revealed that elevated urinary excretion of alpha-aminoadipic
      semialdehyde is not only found in patients with pyridoxine-dependent epilepsy but
      is also seen in patients with molybdenum cofactor deficiency and isolated
      sulphite oxidase deficiency. This should be taken into account when interpreting
      the laboratory data. Sulphite was shown to inhibit alpha-aminoadipic semialdehyde
      dehydrogenase in vitro.

PMID- 22403018
TI  - Gene therapy for metabolic disorders: an overview with a focus on urea cycle
      disorders.
AB  - Many metabolic diseases are compelling candidates for gene therapy, and are the
      subject of vigorous pre-clinical research. Successful phenotype correction in
      mouse models is now commonplace and research effort is increasingly being
      directed towards addressing the translational challenges inherent in human
      clinical trials. This paper places current efforts to develop gene therapy
      approaches to metabolic disease in historical context and describes contemporary
      research in the authors' laboratory on urea cycle defects, particularly ornithine
      transcarbamylase deficiency, in a manner that is illustrative of the general
      state of the field.

PMID- 22403019
TI  - Lysine triggers apoptosis through a NADPH oxidase-dependent mechanism in human
      renal tubular cells.
AB  - Progressive chronic kidney disease (CKD) is common in lysinuric protein
      intolerance (LPI), a primary inherited aminoaciduria characterized by massive
      Lysine excretion in urine. However, by which mechanisms Lysine may cause kidney
      damage to tubule cells is still not understood. This study determined whether
      Lysine overloading of human proximal tubular cells (HK-2) in culture enhances
      apoptotic cell loss and its associated mechanisms. Overloading HK-2 with Lysine
      levels reproducing those observed in urine of patients affected by LPI (10 mM)
      increased apoptosis (+30%; p < 0.01 vs.C), as well as Bax and Apaf-1 expressions
      (+30-50% p < 0.05), while downregulated Bcl-2 (-40% p < 0.05). Apoptosis induced
      by high Lysine was no longer observed after addition of caspase-9 and caspase-3
      inhibitors while caspase-8 inhibitor had no protective effect. High Lysine
      induced elevations in ROS generation and NADPH oxidase subunits mRNAs (p22 (phox)
      +106 +/- 23%, p67 (phox) +108 +/- 22% and gp91 (phox) +75 +/- 4% p < 0.05-0.01).
      In addition, the NADPH oxidase inhibitor DPI prevented both ROS production and
      apoptosis. Treating HK-2 with antioxidants, such as Cysteine and its analog, N
      acetyl-L-cysteine (NAC), rescued the HK-2 from apoptosis induced by Lysine. In
      summary, our data show that high Lysine in vitro increases the permissiveness of
      proximal tubule kidney cells to apoptosis by triggering a pathway involving NADPH
      oxidase signaling. This event may represent a key cellular effect in the
      increasing the susceptibility of human tubular cells to apoptosis when the
      tubules cope with a high Lysine load. This effect is instrumental to renal damage
      and disease progression in patients with LPI.

PMID- 22403021
TI  - Cultural directions and origins of everyday decisions.
AB  - Decisions are made by individuals in all societies. Reasons for decisions are
      difficult to locate, yet configure cultural thinking. While taking decisions
      people can be culture objective and culture subjective at the same time. Methods
      in research focus on the universal features or etic, and culture specific
      features or emic, of the construct of decision making. In the methods used to
      research decision making lie several answers to the question of how people make
      decisions. Isolating features of the emic of decision making can be useful in
      tracing pathways to its etic. The unity of cultural individualism and
      collectivism steer thinking processes of individuals. As a cognitive undertaking
      decision making experiences the effects of the larger culture, but the domains of
      decision making determine in what manner and to what extent these effects will be
      manifest. Decision making is at once subjective and unconscious, culturally
      guided and idiosyncratically steered, self-oriented and other-related,
      situationally derived and universally operationalized.

PMID- 22403020
TI  - Adenosine, dopamine and serotonin receptors imbalance in lymphocytes of Lesch
      Nyhan patients.
AB  - Lesch-Nyhan disease (LND) is caused by complete deficiency of the hypoxanthine
      guanine phosphoribosyltransferase enzyme. It is characterized by overproduction
      of uric acid, jointly with severe motor disability and self-injurious behaviour
      which physiopathology is unknown. These neurological manifestations suggest a
      dysfunction in the basal ganglia, and three neurotransmitters have been
      implicated in the pathogenesis of the disease: dopamine, adenosine and serotonin.
      All of them are implicated in motor function and behaviour, and act by binding to
      specific G-protein coupled receptors in the synaptic membrane where they seem to
      be integrated through receptor-receptor interactions. In this work we have
      confirmed at protein level the previously reported increased expression of DRD5
      and the variably aberrant expression of ADORA2A, in LND PBL respect to control
      PBL. We have also described, for the first time, a decreased expression and
      protein level of 5-HTR1A in LND PBL respect to control PBL. If these results were
      confirmed in the Lesch-Nyhan patients basal ganglia cells, this would support the
      hypothesis that pathogenesis of neurological manifestations of Lesch-Nyhan
      patients may be related to an imbalance of neurotransmitters, rather than to the
      isolated disturbance of one of the neurotransmitters, and this fact should be
      taken into account in the design of pharmacologic treatment for their motor and
      behavioural disturbances.

PMID- 22403022
TI  - The hydrogen-deuterium exchange at alpha-carbon atom in N,N,N-trialkylglycine
      residue: ESI-MS studies.
AB  - Derivatization of peptides as quaternary ammonium salts (QAS) is a known method
      for sensitive detection by electrospray ionization tandem mass spectrometry.
      Hydrogens at alpha-carbon atom in N,N,N-trialkylglycine residue can be easily
      exchanged by deuterons. The exchange reaction is base-catalyzed and is
      dramatically slow at lower pH. Introduced deuterons are stable in acidic aqueous
      solution and are not back-exchanged during LC-MS analysis. Increased ionization
      efficiency, provided by the fixed positive charge on QAS group, as well as the
      deuterium labeling, enables the analysis of trace amounts of peptides.

PMID- 22403023
TI  - Locust primary neuronal culture for the study of synaptic transmission.
AB  - We have designed a cell culture system for thoracic neurons of adult Locusta
      migratoria that enables the establishment of functional synapses in vitro. Patch
      clamp recordings revealed three different neuron classes. About half of the
      neurons (47%) had unexcitable somata with outward and no inward conductance. The
      other half generated either single (37%) or multiple action potentials (18%) and
      differed mainly in lower outward conductance. Selectively stained motor neurons
      were analyzed to demonstrate varied physiological properties due to culture
      conditions. Using paired patch clamp recordings we demonstrate directly synaptic
      transmission in morphologically connected neurons in vitro. Presynaptic
      stimulation resulted in postsynaptic potentials in 42 pairs of neurons tested,
      independent of the type of neuron. According to pharmacological experiments most
      of these synapses were either glutamatergic or GABAergic. In addition to these
      chemical synapses, electrical synapses were found. With the demonstration of
      synapse formation in cell culture of adult locust neurons, this study provides
      the basis for the future analysis of more defined insect neuronal circuits in
      culture.

PMID- 22403024
TI  - Protein encapsulation in unilamellar liposomes: high encapsulation efficiency and
      a novel technique to assess lipid-protein interaction.
AB  - PURPOSE: To encapsulate a large amount of protein (superoxide dismutase, SOD)
      into unilamellar liposomes using a simple process and to investigate the lipid
      protein interaction. METHOD: To achieve protein encapsulation, preformed
      unilamellar empty liposomes were mixed with SOD and subjected to freeze-thaw
      cycling. To investigate the lipid-protein interaction, a novel light scattering
      technique was used. RESULTS: Up to 50% protein encapsulation was achieved at ~150
      nm. There was no significant change in particle size following the freeze-thaw
      cycling. SOD had a strong interaction with DPPC liposomes containing high
      concentration of cholesterol. Light scattering data revealed that in some cases
      the SOD molecules were present inside the lipid bilayer. CONCLUSIONS: The method
      reported here allows great flexibility in the manufacturing process as the
      liposome preparation and protein-loading operations can be separated.
      Accordingly, empty liposomes can be prepared without concern about protein
      stability, making the manufacturing process more flexible and easy to control and
      ultimately leading to improved product quality. To explain the SOD-lipid
      interaction, a "pocket-embedding" theory was proposed. The encapsulation method
      reported here can be applied to hydrophilic small molecules as well as most
      hydrophilic proteins to achieve high encapsulation efficiency.

PMID- 22403025
TI  - Neuropathology of wild-type and nef-attenuated T cell tropic simian
      immunodeficiency virus (SIVmac32H) and macrophage tropic neurovirulent SIVmac17E
      Fr in cynomolgus macaques.
AB  - The neuropathology of simian immunodeficiency (SIV) infection in cynomolgus
      macaques (Macaca fascicularis) was investigated following infection with either T
      cell tropic SIVmacJ5, SIVmacC8 or macrophage tropic SIVmac17E-Fr. Formalin fixed,
      paraffin embedded brain tissue sections were analysed using a combination of in
      situ techniques. Macaques infected with either wild-type SIVmacJ5 or
      neurovirulent SIVmac17E-Fr showed evidence of neuronal dephosphorylation, loss of
      oligodendrocyte and CCR5 staining, lack of microglial MHC II expression,
      infiltration by CD4+ and CD8+ T cells and mild astrocytosis. SIVmacJ5-infected
      animals exhibited activation of microglia whilst those infected with SIVmac17E-Fr
      demonstrated a loss of microglia staining. These results are suggestive of
      impaired central nervous system (CNS) physiology. Furthermore, infiltration by T
      cells into the brain parenchyma indicated disruption of the blood brain barrier
      (BBB). Animals infected with the Deltanef-attenuated SIVmacC8 showed microglial
      activation and astrogliosis indicative of an inflammatory response, lack of MHC
      II and CCR5 staining and infiltration by CD8+ T cells. These results demonstrate
      that the SIV infection of cynomolgus macaque can be used as a model to replicate
      the range of CNS pathologies observed following HIV infection of humans and to
      investigate the pathogenesis of HIV associated neuropathology.

PMID- 22403026
TI  - Plasma gelsolin accumulates in macrophage nodules in brains of simian
      immunodeficiency virus infected rhesus macaques.
AB  - Plasma gelsolin (pGSN), an isoform 1, is secreted by various types of cells in
      the central nervous system (CNS) and periphery, but not by the liver. pGSN
      circulates in blood and cerebrospinal fluid (CSF); however, its concentration in
      CSF is approximately twenty times lower than in plasma. It has been shown that
      several types of cells such as oligodendrocytes, neurons, and/or astrocytes
      contribute to the overall pool of pGSN in the CNS. Further, it has been
      postulated that pGSN plays multiple roles during microbial infection and
      modulates inflammatory responses; however, the exact mechanism of regulation is
      not known. We previously showed that levels of pGSN in CSF of individuals with
      advanced neurocognitive impairment due to HIV infection of the brain are
      decreased. Here, we show that macrophages express significant amounts of pGSN in
      response to HIV infection in vitro. Using immunohistochemistry of simian
      immunodeficiency virus infected rhesus monkey brains, we show that increased
      levels of pGSN are present in macrophage nodules creating locally a high level of
      this protein within the brain. This may not be reflected by the overall decreased
      level in the distinct CSF compartment.

PMID- 22403027
TI  - Immunization with structural and non-structural proteins of Theiler's murine
      encephalomyelitis virus alters demyelinating disease.
AB  - Theiler's murine encephalomyelitis virus (TMEV) causes a demyelinating disease
      similar to multiple sclerosis in the central nervous system (CNS) of susceptible
      SJL/J mice. Immune responses to TMEV contribute to viral clearance as well as to
      demyelination. We constructed recombinant vaccinia viruses (VV) that encode each
      or all of the capsid proteins (VV(VP1), VV(VP2), VV(VP3), VV(VP4), and VV(all))
      or non-structural proteins (VV(P2), VV(P2P3), and VV(3'P3)) of the Daniels strain
      of TMEV. To determine the role of each of the coding regions of TMEV in vivo, we
      immunized SJL/J mice with each recombinant VV, with or without subsequent TMEV
      infection. The groups of mice were compared clinically, immunologically, and
      histologically. No mice immunized with any recombinant VV without subsequent TMEV
      infection developed demyelination. However, antibody responses to TMEV were
      detected in mice immunized with VV(all). In addition, in some mice, VV(P2)
      immunization induced mild meningitis. VV(VP3) or VV(VP4) immunization of mice
      prior to TMEV infection ameliorated TMEV-induced pathology or clinical signs of
      disease. The beneficial effect of VP4 immunization was also seen through DNA
      immunization with a plasmid encoding VP4 and leader prior to TMEV infection.
      Therefore, vaccination against not only surface capsid proteins (VV(VP3) and
      VV(all)) but also non-surface capsid protein (VV(VP4)), and non-structural
      proteins (VV(P2)) can elicit immune responses to virus or modulate subsequent
      viral-induced CNS disease.

PMID- 22403028
TI  - Propionibacterium acnes brain abscess in a patient with HIV-1 infection.

PMID- 22403029
TI  - Acute exercise improves physical sexual arousal in women taking antidepressants.
AB  - BACKGROUND: Antidepressants can impair sexual arousal. Exercise increases genital
      arousal in healthy women, likely due to increasing sympathetic nervous system
      (SNS) activity. PURPOSE: Test if exercise increases genital arousal in women
      taking antidepressants, including selective serotonin reuptake inhibitors
      (SSRIs), which suppress SNS activity, and selective serotonin and norepinephrine
      reuptake inhibitors (SNRIs), which suppress the SNS less. METHOD: Women reporting
      antidepressant-related sexual arousal problems (N = 47) participated in three
      counterbalanced sessions where they watched an erotic film while we recorded
      genital and SNS arousal. In two sessions, women exercised for 20 min, either 5 or
      15 min prior to the films. RESULTS: During the no-exercise condition, women
      taking SSRIs showed significantly less genital response than women taking SNRIs.
      Exercise prior to sexual stimuli increased genital arousal in both groups. Women
      reporting greater sexual dysfunction had larger increases in genital arousal post
      exercise. For women taking SSRIs, genital arousal was linked to SNS activity.
      CONCLUSIONS: Exercise may improve antidepressant-related genital arousal
      problems.

PMID- 22403030
TI  - MicroRNA profiles and their control of male gametophyte development in rice.
AB  - Plant microRNAs (miRNAs) act as negative regulators of gene expression by slicing
      target transcripts or inhibiting translation. A number of miRNAs play important
      roles in development. In order to investigate the potential function of miRNAs
      during male gametogenesis in rice, we obtained both gene and small RNA expression
      profiles by combining microarray and high-throughput sequencing technologies.
      From the microarray datasets, 2,925 male gametophyte-specific genes were
      identified, including 107 transcription factors and three significant Argonaute
      genes (AGO12, AGO13, and AGO17). From the sRNA-Seq datasets, 104 unique miRNAs
      (miRus) were identified, including 47 known miRus and 57 novel miRus;
      interestingly, most of the new miRus are pollen-specific and not conserved among
      species. Furthermore, an interactive network of miRNA-target was constructed
      based on the two datasets. By employing enrichment analysis, the miRNA-regulated
      targets were found to be involved in both the up and down pathways, but
      predominantly in the down pathways, including 37 GO biological processes and 32
      KEGG pathways. These findings indicate that miRNAs play a broad regulatory role
      during male gametophyte development in rice.

PMID- 22403032
TI  - The complete chloroplast genome of Ginkgo biloba reveals the mechanism of
      inverted repeat contraction.
AB  - We determined the complete chloroplast genome (cpDNA) of Ginkgo biloba (common
      name: ginkgo), the only relict of ginkgophytes from the Triassic Period. The
      cpDNA molecule of ginkgo is quadripartite and circular, with a length of 156,945
      bp, which is 6,458 bp shorter than that of Cycas taitungensis. In ginkgo cpDNA,
      rpl23 becomes pseudo, only one copy of ycf2 is retained, and there are at least
      five editing sites. We propose that the retained ycf2 is a duplicate of the
      ancestral ycf2, and the ancestral one has been lost from the inverted repeat A
      (IR(A)). This loss event should have occurred and led to the contraction of IRs
      after ginkgos diverged from other gymnosperms. A novel cluster of three transfer
      RNA (tRNA) genes, trnY-AUA, trnC-ACA, and trnSeC-UCA, was predicted to be located
      between trnC-GCA and rpoB of the large single-copy region. Our phylogenetic
      analysis strongly suggests that the three predicted tRNA genes are duplicates of
      trnC-GCA. Interestingly, in ginkgo cpDNA, the loss of one ycf2 copy does not
      significantly elevate the synonymous rate (Ks) of the retained copy, which
      disagrees with the view of Perry and Wolfe (2002) that one of the two-copy genes
      is subjected to elevated Ks when its counterpart has been lost. We hypothesize
      that the loss of one ycf2 is likely recent, and therefore, the acquired Ks of the
      retained copy is low. Our data reveal that ginkgo possesses several unique
      features that contribute to our understanding of the cpDNA evolution in seed
      plants.

PMID- 22403033
TI  - Identification and properties of 1,119 candidate lincRNA loci in the Drosophila
      melanogaster genome.
AB  - The functional repertoire of long intergenic noncoding RNA (lincRNA) molecules
      has begun to be elucidated in mammals. Determining the biological relevance and
      potential gene regulatory mechanisms of these enigmatic molecules would be
      expedited in a more tractable model organism, such as Drosophila melanogaster. To
      this end, we defined a set of 1,119 putative lincRNA genes in D. melanogaster
      using modENCODE whole transcriptome (RNA-seq) data. A large majority (1.1 of 1.3
      Mb; 85%) of these bases were not previously reported by modENCODE as being
      transcribed. Significant selective constraint on the sequences of these loci
      predicts that virtually all have sustained functionality across the Drosophila
      clade. We observe biases in lincRNA genomic locations and expression profiles
      that are consistent with some of these lincRNAs being involved in the regulation
      of neighboring protein-coding genes with developmental functions. We identify
      lincRNAs that may be important in the developing nervous system and in male
      specific organs, such as the testes. LincRNA loci were also identified whose
      positions, relative to nearby protein-coding loci, are equivalent between D.
      melanogaster and mouse. This study predicts that the genomes of not only
      vertebrates, such as mammals, but also an invertebrate (fruit fly) harbor large
      numbers of lincRNA loci. Our findings now permit exploitation of Drosophila
      genetics for the investigation of lincRNA mechanisms, including lincRNAs with
      potential functional analogues in mammals.

PMID- 22403034
TI  - Targeting, universalism, and single-mother poverty: a multilevel analysis across
      18 affluent democracies.
AB  - We examine the influence of individual characteristics and targeted and universal
      social policy on single-mother poverty with a multilevel analysis across 18
      affluent Western democracies. Although single mothers are disproportionately poor
      in all countries, there is even more cross-national variation in single-mother
      poverty than in poverty among the overall population. By far, the United States
      has the highest rate of poverty among single mothers among affluent democracies.
      The analyses show that single-mother poverty is a function of the household's
      employment, education, and age composition, and the presence of other adults in
      the household. Beyond individual characteristics, social policy exerts
      substantial influence on single-mother poverty. We find that two measures of
      universal social policy significantly reduce single-mother poverty. However, one
      measure of targeted social policy does not have significant effects, and another
      measure is significantly negative only when controlling for universal social
      policy. Moreover, the effects of universal social policy are larger. Additional
      analyses show that universal social policy does not have counterproductive
      consequences in terms of family structure or employment, while the results are
      less clear for targeted social policy. Although debates often focus on altering
      the behavior or characteristics of single mothers, welfare universalism could be
      an even more effective anti-poverty strategy.

PMID- 22403035
TI  - International fertility change: new data and insights from the developmental
      idealism framework.
AB  - Many scholars have offered structural and ideational explanations for the
      fertility changes occurring around the world. This paper focuses on the influence
      of developmental idealism-a schema or set of beliefs endorsing development,
      fertility change, and causal connections between development and fertility.
      Developmental idealism is argued to be an important force affecting both
      population policy and the fertility behavior of ordinary people. We present new
      survey data from ordinary people in six countries-Argentina, China, Egypt, Iran,
      Nepal, and the United States-about the extent to which developmental idealism is
      known and believed. We ask individuals if they believe that fertility and
      development are correlated, that development is a causal force in changing
      fertility levels, and that fertility declines enhance the standard of living and
      intergenerational relations. We also ask people about their expectations
      concerning future trends in fertility in their countries and whether they approve
      or disapprove of the trends they expect. The data show widespread linkage in the
      minds of ordinary people between fertility and development. Large fractions of
      people in these six settings believe that fertility and development are
      correlated, that development reduces fertility, and that declines in fertility
      foster development. Many also expect and endorse future declines in fertility.

PMID- 22403036
TI  - Optimization of variable fluorescence measurements of phytoplankton communities
      with cyanobacteria.
AB  - Excitation-emission fluorescence matrices of phytoplankton communities were
      simulated from laboratory-grown algae and cyanobacteria cultures, to define the
      optical configurations of theoretical fluorometers that either minimize or
      maximize the representation of these phytoplankton groups in community variable
      fluorescence measurements. Excitation sources that match the photosystem II
      (PSII) action spectrum of cyanobacteria do not necessarily lead to equal
      representation of cyanobacteria in community fluorescence. In communities with an
      equal share of algae and cyanobacteria, inducible PSII fluorescence in algae can
      be retrieved from community fluorescence under blue excitation (450-470 nm) with
      high accuracy (R (2) = 1.00). The highest correlation between community and
      cyanobacterial variable fluorescence is obtained under orange-red excitation in
      the 590-650 nm range (R (2) = 0.54). Gaussian band decomposition reveals that in
      the presence of cyanobacteria, the emission detection slit must be narrow (up to
      10 nm) and centred on PSII chlorophyll-a emission (~683 nm) to avoid severe
      dampening of the signal by weakly variable phycobilisomal fluorescence and non
      variable photosystem I fluorescence. When these optimizations of the optical
      configuration of the fluorometer are followed, both cyanobacterial and algal
      cultures in nutrient replete exponential growth exhibit values of the maximum
      quantum yield of charge separation in PSII in the range of 0.65-0.7.

PMID- 22403037
TI  - Sensory experience modifies spontaneous state dynamics in a large-scale barrel
      cortical model.
AB  - Experimental evidence suggests that spontaneous neuronal activity may shape and
      be shaped by sensory experience. However, we lack information on how sensory
      experience modulates the underlying synaptic dynamics and how such modulation
      influences the response of the network to future events. Here we study whether
      spike-timing-dependent plasticity (STDP) can mediate sensory-induced
      modifications in the spontaneous dynamics of a new large-scale model of layers
      II, III and IV of the rodent barrel cortex. Our model incorporates significant
      physiological detail, including the types of neurons present, the probabilities
      and delays of connections, and the STDP profiles at each excitatory synapse. We
      stimulated the neuronal network with a protocol of repeated sensory inputs
      resembling those generated by the protraction-retraction motion of whiskers when
      rodents explore their environment, and studied the changes in network dynamics.
      By applying dimensionality reduction techniques to the synaptic weight space, we
      show that the initial spontaneous state is modified by each repetition of the
      stimulus and that this reverberation of the sensory experience induces long-term,
      structured modifications in the synaptic weight space. The post-stimulus
      spontaneous state encodes a memory of the stimulus presented, since a different
      dynamical response is observed when the network is presented with shuffled
      stimuli. These results suggest that repeated exposure to the same sensory
      experience could induce long-term circuitry modifications via 'Hebbian' STDP
      plasticity.

PMID- 22403038
TI  - Update on anterior ankle impingement.
AB  - Anterior ankle impingement results from an impingement of the ankle joint by a
      soft tissue or osteophyte formation at the anterior aspect of the distal tibia
      and talar neck. It often occurs secondary to direct trauma (impaction force) or
      repetitive ankle dorsiflexion (repetitive impaction and traction force). Chronic
      ankle pain, swelling, and limitation of ankle dorsiflexion are common complaints.
      Imaging is valuable for diagnosis of the bony impingement but not for the soft
      tissue impingement, which is based on clinical findings. MR imaging and MR
      arthrography are helpful in doubtful diagnoses and the identification of
      associated injuries. Recommended methods for initial management include rest,
      physical therapy, and shoe modification. If nonoperative treatment fails,
      arthroscopic bony or soft tissue debridement both offer significant symptomatic
      relief with long-term positive outcomes in cases that have no significant
      arthritic change, associated ligament laxity, and chondral lesion.

PMID- 22403039
TI  - Advances in psychotherapy for generalized anxiety disorder.
AB  - Since the introduction of generalized anxiety disorder into the diagnostic system
      for psychiatric conditions, scientists have worked to develop effective
      treatments for the amelioration of chronic, excessive worry. In addition to
      traditional cognitive-behavioral therapy, more recent advances have focused on
      treatments targeting intolerance of uncertainty, meta-cognitions, emotion
      dysregulation, lack of acceptance of internal experiences, and emotional
      contrasts. This article reviews these therapeutic approaches and summarizes
      recent publications relevant to the psychological treatment of worry and
      generalized anxiety disorder.

PMID- 22403040
TI  - The Fatigue Associated with Depression Questionnaire (FAsD): responsiveness and
      responder definition.
AB  - PURPOSE: The Fatigue Associated with Depression Questionnaire (FAsD) was
      developed to assess fatigue and its impact among patients with depression. The
      purpose of this study was to examine the questionnaire's responsiveness to change
      and identify a responder definition for interpretation of treatment-related
      changes. METHODS: Data were collected at baseline and at 6 weeks from patients
      with depression starting treatment with a new antidepressant. RESULTS: Of the 96
      participants, 55.2% were women, with a mean age of 43.4 years. The total score
      and both subscales demonstrated statistically significant change with moderate to
      large effect sizes (absolute values >= 0.76). FAsD change scores were
      significantly correlated with change on the Brief Fatigue Inventory (r >= 0.73; p
      < 0.001). FAsD mean change scores discriminated among patient subgroups differing
      by degree of improvement in patient- and clinician-reported fatigue and
      depression. Responder definition for the two subscales and total score (0.67,
      0.57, 0.62) was estimated primarily based on mean change among patients who
      reported a small but important improvement in fatigue. DISCUSSION: The FAsD was
      responsive to change, and the responder definition may be used when interpreting
      treatment-related change. Results add to previous findings suggesting the FAsD is
      a useful measure of fatigue among patients with depression.

PMID- 22403041
TI  - Physical activity, self-efficacy, and health-related quality of life in persons
      with multiple sclerosis: analysis of associations between individual-level
      changes over one year.
AB  - BACKGROUND: Physical activity and self-efficacy represent behavioral and
      psychological factors, respectively, that are compromised in persons with
      multiple sclerosis (MS), but might be modifiable through intervention and result
      in better health-related quality of life (HRQOL). PURPOSE: The present study
      adopted a panel research design and examined the associations between individual
      level changes in physical activity, self-efficacy, and HRQOL over a one-year
      period in persons with MS. METHOD: The sample consisted of 269 persons with
      relapsing-remitting MS who completed the Godin Leisure-Time Questionnaire
      (GLTEQ), Multiple Sclerosis Self-Efficacy (MSSE) Scale, and Multiple Sclerosis
      Quality of Life-29 (MSIS-29) Scale on two occasions that were separated by 1
      year. The data were analyzed using panel analysis in Mplus 3.0. RESULTS: The
      initial panel analysis indicated that individual-level change in physical
      activity was associated with individual-level change in both physical and
      psychological HRQOL. The subsequent panel analysis indicated that (a) individual
      level change in self-efficacy for functioning with MS was associated with
      individual-level change in physical HRQOL, whereas individual-level change in
      self-efficacy for control was associated with individual-level change in
      psychological HRQOL; (b) individual-level change in self-efficacy for functioning
      with MS, but not self-efficacy for control, mediated the association between
      individual-level change in physical activity and physical HRQOL; and (c)
      individual-level change in self-efficacy for controlling MS was the strongest
      predictor of individual-level change in HRQOL. CONCLUSION: Physical activity and
      self-efficacy both might be important targets of subsequent behavioral and self
      management interventions for improving the HRQOL of persons with MS, although
      self-efficacy is seemingly more important than physical activity.

PMID- 22403042
TI  - Treatment of atrioventricular nodal re-entrant tachycardia by cryoablation with
      an 8-mm-tip catheter versus radiofrequency ablation.
AB  - PURPOSE: Catheter cryoablation (CRYO) may eliminate inadvertent atrioventricular
      block (AVB) in the treatment of atrioventricular nodal reentrant tachycardia
      (AVNRT). However, higher recurrence was observed with CRYO delivered by 4 mm or 6
      mm-tip catheter. This study was performed to investigate whether a comparably low
      treatment failure and recurrence rate as in radiofrequency (RF) ablation is
      achievable by CRYO with an 8-mm-tip catheter. METHODS: This is a retrospective
      case-control study including 40 patients with AVNRT treated with CRYO (n = 20)
      using an 8 mm-tip catheter or RF ablation (n = 20) from March 2009 to March 2011.
      Treatment failure was defined as the composite of acute procedural failure
      including inadvertent permanent AVB and documented recurrence. RESULTS: Acute
      procedural success of 90% (18/20) and 95% (19/20) were achieved in CRYO and RF
      ablation group, respectively (p = 0.998), with no permanent AVB in either group.
      With Kaplan-Meier analysis, there was no significant difference between the
      treatment groups in terms of recurrence rate (5.6% [1/18] vs. 0%; log-rank test p
      = 0.304) and treatment failure (15% [3/20] vs. 5% [1/20]; log-rank test p =
      0.301). Shorter fluoroscopy time (15 +/- 8.6 vs. 25.2 +/- 12.1 min; p = 0.005)
      and more energy applications (median 4 [2-15] vs. 2 [1-8]; p = 0.005) were
      observed in the CRYO group compared with RF ablation group. CONCLUSIONS: Compared
      to RF ablation, CRYO with an 8-mm-tip catheter for treating AVNRT achieves a
      comparable acute procedural success, comparably low recurrence rate and composite
      endpoint of treatment failure. Shorter fluoroscopy time and more energy
      applications were observed in the CRYO group.

PMID- 22403043
TI  - Ablation for atrial fibrillation: what are acceptable levels of experience,
      efficacy, and complications?

PMID- 22403045
TI  - Rare human skin infection with Corynebacterium ulcerans: transmission by a
      domestic cat.
AB  - Corynebacterium ulcerans is mainly known for its ability to cause animal
      infections. Some strains of C. ulcerans produce diphtheria toxin, which can cause
      life-threatening cardiopathies and neuropathies in humans. Human cutaneous C.
      ulcerans infection is a very rare disease that mimics classical cutaneous
      diphtheria. We present a very rare case of a C. ulcerans skin infection caused by
      a non-diphtheria toxin-producing strain of C. ulcerans that resolved after 3
      weeks of therapy with amoxicillin-clavulanate. A pet cat was the probable source
      of infection. The presence of C. ulcerans in the mouth of the cat was confirmed
      by 16S rRNA gene analysis and the API Coryne system. In cases of human infection
      with potentially toxigenic corynebacteria, it is important to determine the
      species and examine the isolate for diphtheria toxin production. If toxigenicity
      is present, diphtheria antitoxin should be administered immediately. Carriers and
      potential infectious sources of C. ulcerans include not only domestic livestock
      but also pet animals. For the primary prevention of disease caused by diphtheria
      toxin-producing corynebacteria, vaccination with diphtheria toxoid is
      recommended.

PMID- 22403046
TI  - Initial lesion volume is an independent predictor of clinical stroke outcome at
      day 90: an analysis of the Virtual International Stroke Trials Archive (VISTA)
      database.
AB  - BACKGROUND AND PURPOSE: Age and National Institutes of Health Stroke Scale early
      after stroke onset have been identified as important determinants of final stroke
      outcome. We analyzed the Virtual International Stroke Trials Archive (VISTA)
      database to define the influence of infarct or hemorrhagic volume on clinical
      outcome after stroke. METHODS: All patients were extracted from VISTA where
      infarct or hemorrhage volume information was available (n=2538; most images
      obtained by CT within 72 hours after stroke onset with a subset of MRI data
      included, volumes calculated by the ABC/2 approximation method). We used
      multivariate regression models to study the influence of age, National Institutes
      of Health Stroke Scale at baseline, and initial infarct/hemorrhage volume on
      clinical outcome (modified Rankin Scale, National Institutes of Health Stroke
      Scale, mortality) at day 90. RESULTS: We find that in a large cohort of >1800
      patients with ischemic stroke, initial lesion size is a strong and independent
      predictor of stroke outcome in a statistical regression model that also accounts
      for age and National Institutes of Health Stroke Scale at baseline (P<0.0001).
      The use of infarct/hemorrhage volume as an additional predictive factor further
      reduces the fraction of unexplained variance in outcome by approximately 15%
      (R(2) of 0.41 versus 0.26 in a model without lesion volume). The predictive
      strength of initial lesion size is only marginally influenced by image modality
      or time point of image acquisition within the first 72 hours. The model was
      equally valid for both ischemic and hemorrhagic strokes. CONCLUSIONS:
      Infarct/hemorrhage volume at baseline together with age and National Institutes
      of Health Stroke Scale at baseline should be used in the effect analysis of
      future therapeutic stroke trials to improve power.

PMID- 22403047
TI  - Randomized trial of clazosentan in patients with aneurysmal subarachnoid
      hemorrhage undergoing endovascular coiling.
AB  - BACKGROUND AND PURPOSE: Clazosentan, an endothelin receptor antagonist, has been
      shown to reduce vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).
      CONSCIOUS-3 assessed whether clazosentan reduced vasospasm-related morbidity and
      all-cause mortality postaSAH secured by endovascular coiling. METHODS: This
      double-blind, placebo-controlled, phase III trial randomized patients with aSAH
      secured by endovascular coiling to <= 14 days intravenous clazosentan (5 or 15
      mg/h) or placebo. The primary composite end point (all-cause mortality; vasospasm
      related new cerebral infarcts or delayed ischemic neurological deficits; rescue
      therapy for vasospasm) was evaluated 6 weeks postaSAH. The main secondary end
      point was dichotomized extended Glasgow Outcome Scale (week 12). RESULTS:
      CONSCIOUS-3 was halted prematurely following completion of CONSCIOUS-2; 577/1500
      of planned patients (38%) were enrolled and 571 were treated (placebo, n=189;
      clazosentan 5 mg/h, n=194; clazosentan 15 mg/h, n=188). The primary end point
      occurred in 50/189 of placebo-treated patients (27%), compared with 47/194
      patients (24%) treated with clazosentan 5 mg/h (odds ratio [OR], 0.786; 95% CI,
      0.479-1.289; P=0.340), and 28/188 patients (15%) treated with clazosentan 15 mg/h
      (OR, 0.474; 95% CI, 0.275-0.818; P=0.007). Poor outcome (extended Glasgow Outcome
      Scale score <= 4) occurred in 24% of patients with placebo, 25% of patients with
      clazosentan 5 mg/h (OR, 0.918; 95% CI, 0.546-1.544; P=0.748), and 28% of patients
      with clazosentan 15 mg/h (OR, 1.337; 95% CI, 0.802-2.227; P=0.266). Pulmonary
      complications, anemia, and hypotension were more common in patients who received
      clazosentan than in those who received placebo. At week 12, mortality was 6%, 4%,
      and 6% with placebo, clazosentan 5 mg/h, and clazosentan 15 mg/h, respectively.
      CONCLUSIONS: Clazosentan 15 mg/h significantly reduced postaSAH vasospasm-related
      morbidity/all-cause mortality; however, neither dose improved outcome (extended
      Glasgow Outcome Scale).

PMID- 22403048
TI  - Alcohol consumption and risk of stroke in women.
AB  - BACKGROUND AND PURPOSE: Light-to-moderate alcohol consumption has been
      consistently associated with lower risk of heart disease, but data for stroke are
      less certain. A lower risk of stroke with light-to-moderate alcohol intake has
      been suggested, but the dose response among women remains uncertain and the data
      in this subgroup have been sparse. METHODS: A total of 83 578 female participants
      of the Nurses' Health Study who were free of diagnosed cardiovascular disease and
      cancer at baseline were followed-up from 1980 to 2006. Data on self-reported
      alcohol consumption were assessed at baseline and updated approximately every 4
      years, whereas stroke and potential confounder data were updated at baseline and
      biennially. Strokes were classified according to the National Survey of Stroke
      criteria. RESULTS: We observed 2171 incident strokes over 1 695 324 person-years.
      In multivariable adjusted analyses, compared to abstainers, the relative risks of
      stroke were 0.83 (95% CI, 0.75-0.92) for <5 g/d, 0.79 (95% CI, 0.70-0.90) for 5
      to 14.9 g/d, 0.87 (0.72-1.05) for 15 to 29.9 g/d, and 1.06 (95% CI, 0.86-1.30)
      for 30 to 45 g/d. Results were similar for ischemic and hemorrhagic stroke.
      CONCLUSIONS: Light-to-moderate alcohol consumption was associated with a lower
      risk of total stroke. In this population of women with modest alcohol
      consumption, an elevated risk of total stroke related to alcohol was not
      observed.

PMID- 22403049
TI  - Accuracy of a novel risk index combining degree of stenosis of the carotid artery
      and plaque surface echogenicity.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine the accuracy
      of a risk index in symptomatic or asymptomatic carotid stenoses. METHODS:
      Consecutive patients presenting 50% to 99% carotid stenoses were included. A
      semiautomated gray scale-based color mapping (red, yellow, and green) of the
      whole plaque and of its surface was achieved. Surface was defined as the region
      located between the lumen (Level 0) and, respectively, 0.5, 1, 1.5, and 2 mm.
      Risk index was based on a combination of degree of stenosis and the proportion of
      the red color (reflecting low echogenicity) on the surface or on the whole
      plaque. RESULTS: There were 67 (36%) symptomatic and 117 (64%) asymptomatic
      carotid stenoses. Risk index values were higher among symptomatic stenoses (0.46
      mean versus 0.29; P<0.0001); on receiver operating characteristic curves, risk
      index presented a stronger predictive power compared with degree of stenosis or
      surface echogenicity alone. Also, in a regression model including age, gender,
      degree of stenosis, surface echogenicity, gray median scale of the whole plaque,
      and risk index, risk index measured within the surface region located at 0.5 mm
      from the lumen was the only parameter significantly associated with the presence
      of symptoms (OR, 4.89; 95% CI, 2.7-8.7; P=0.0000002). The best criterion to
      differentiate between symptomatic and asymptomatic stenoses was a risk index
      value >0.36 (sensitivity and specificity of 78% and 65%, respectively).
      CONCLUSIONS: Risk index was significantly higher in the presence of symptoms and
      could therefore be a valuable tool to assess the clinical risk of a carotid
      plaque.

PMID- 22403051
TI  - Noncompliance with certain quality indicators is associated with risk-adjusted
      mortality after stroke.
AB  - BACKGROUND AND PURPOSE: To investigate the 30-day and 12-month mortality risks
      among hospitalized stroke patients according to compliance with guideline-based
      process indicators. METHODS: We used data from the Second Stroke Audit and the
      Mortality Register of Catalonia (Spain). The audit retrospectively explored
      quality of stroke care based on compliance with indicators among patients
      discharged from all public hospitals in Catalonia in 2007; they were identified
      and selected through a pre-established sampling method. The magnitude of the
      independent association of each indicator with 30-day and 12-month mortality was
      assessed using logistic regression with generalized estimating equations to
      account for clustering of patients within hospitals. Generalized estimating
      equations modeling was initially restricted to patients alive >72 hours
      poststroke to control for confounding by severity. Analyses were also run in 3
      other samples (all patients, patients alive >7 days, and patients alive >14
      days). RESULTS: Of 1767 stroke admissions in the Second Stroke Audit, 1697
      patients survived >72 hours poststroke. Within this sample, the adjusted 30-day
      mortality risk was negatively associated with nonadherence to different
      indicators, of which only antithrombotics at discharge (OR, 4.3; 95% CI, 1.72
      10.78) remained significant in all data sets. At 12 months, the adjusted
      mortality risk was negatively associated with management of hypertension (OR,
      1.87; 95% CI, 1.22-2.86) and antithrombotics at discharge (OR, 2.79; 95% CI, 1.41
      5.54). Both remained unchanged across different samples. CONCLUSIONS: Assessing
      the impact of quality of stroke care on mortality is complex and is hampered by
      residual confounding, particularly in the short-term. Nevertheless, this study
      suggests that at least a few indicators should be used to monitor quality of
      stroke services.

PMID- 22403050
TI  - Toll-like receptor 7 preconditioning induces robust neuroprotection against
      stroke by a novel type I interferon-mediated mechanism.
AB  - BACKGROUND AND PURPOSE: Systemic administration of Toll-like receptor (TLR) 4 and
      TLR9 agonists before cerebral ischemia have been shown to reduce ischemic injury
      by reprogramming the response of the brain to stroke. Our goal was to explore the
      mechanism of TLR-induced neuroprotection by determining whether a TLR7 agonist
      also protects against stroke injury. METHODS: C57Bl/6, TNF(-/-), interferon (IFN)
      regulatory factor 7(-/-), or type I IFN receptor (IFNAR)(-/-) mice were
      subcutaneously administered the TLR7 agonist Gardiquimod (GDQ) 72 hours before
      middle cerebral artery occlusion. Infarct volume and functional outcome were
      determined after reperfusion. Plasma cytokine responses and induction of mRNA for
      IFN-related genes in the brain were measured. IFNAR(-/-) mice also were treated
      with the TLR4 agonist (lipopolysaccharide) or the TLR9 agonist before middle
      cerebral artery occlusion and infarct volumes measured. RESULTS: The results show
      that GDQ reduces infarct volume as well as functional deficits in mice. GDQ
      pretreatment provided robust neuroprotection in TNF(-/-) mice, indicating that
      TNF was not essential. GDQ induced a significant increase in plasma IFNalpha
      levels and both IRF7(-/-) and IFNAR(-/-) mice failed to be protected, implicating
      a role for IFN signaling in TLR7-mediated protection. CONCLUSIONS: Our studies
      provide the first evidence that TLR7 preconditioning can mediate neuroprotection
      against ischemic injury. Moreover, we show that the mechanism of protection is
      unique from other TLR preconditioning ligands in that it is independent of TNF
      and dependent on IFNAR.

PMID- 22403052
TI  - Impact of thrombolysis on stroke outcome at 12 months in a population: the Bern
      stroke project.
AB  - BACKGROUND AND PURPOSE: Thrombolysis improves outcome of patients with acute
      ischemic stroke, but it is unknown whether thrombolysis has a measurable effect
      on long-term outcome in a defined population. METHODS: We prospectively assessed
      demographic data, management, and outcome of acute ischemic stroke patients
      admitted within 48 hours to 18 primary care hospitals of the canton of Bern (969
      299 inhabitants) during 12 months. Blinded follow-up was obtained at 3 and 12
      months. Predictors of mortality and favorable outcome (modified Rankin Scale
      score <=2) at 3 and 12 months using logistic regression were analyzed. RESULTS:
      From December 2007 to December 2008, 807 patients (mean age, 72 years) were
      included. Median National Institutes of Health Stroke Scale score on admission
      was 5; 107 patients (13%) received intravenous, intra-arterial, or mechanical
      thrombolysis. Estimated cumulative mortality at 3 months was 20.6% and at 12
      months 27.4%. Age 75 years or older, higher National Institutes of Health Stroke
      Scale scores, and higher Charlson comorbidity index were independent predictors
      of mortality at 3 and 12 months. Estimated favorable outcome at 3 months was
      48.2% and at 12 months was 44.6%. Thrombolysis was the only modifiable
      independent predictor of favorable outcome at 3 (relative risk, 1.49; 95% CI,
      1.18-1.89) and 12 months (relative risk, 1.59; 95% CI, 1.24-2.04), whereas age
      younger than 75 years, male gender, National Institutes of Health Stroke Scale
      score <4, and lower Charlson comorbidity index were nonmodifiable predictors.
      CONCLUSIONS: Thirteen percent of acute ischemic stroke patients admitted within
      48 hours to Bernese hospitals underwent thrombolysis, which exerted a measurable
      effect on 3-month outcome in this population. This effect was sustained at 12
      months. Age, stroke severity, Charlson comorbidity index, and male gender were
      independent nonmodifiable predictors of outcome.

PMID- 22403053
TI  - Mechanism of ischemic infarct in spontaneous cervical artery dissection.
AB  - BACKGROUND AND PURPOSE: It is unclear whether strokes in patients with
      spontaneous cervical artery dissection (CAD) are due to secondary thromboembolism
      or to a reduction in cerebral blood flow from the primary cervical lesion. The
      aim of this study was to identify the most likely mechanism of stroke using
      cervical and cerebral imaging parameters in patients with CAD. METHODS: The study
      was approved by the local Ethics Committee. Informed consent was waived. We
      retrospectively evaluated the cerebrovascular ultrasound, cervical MR
      angiography, and stroke brain MRI in consecutive patients with CAD. An embolic
      mechanism was considered in the case of direct visualization of an intracranial
      embolism as a susceptibility vessel sign on T2* or in the case of pial artery
      territory infarction on diffusion-weighted imaging. A hemodynamic mechanism was
      considered in the case of watershed infarction and in the case of an association
      of watershed infarction and pial artery territory infarction when >= 2 of the
      following were present: severe stenotic or occlusive CAD, reduced intracranial
      velocity on cerebrovascular ultrasound or signal on MR angiography, or
      hyperintense vessel sign on fluid-attenuated inversion recovery. The remaining
      patients were considered to have a mixed mechanism. RESULTS: Of 172 consecutive
      patients with CAD, 100 (58%) had acute stroke on diffusion-weighted imaging.
      Stroke was attributed to a thromboembolic mechanism in 85 of 100 patients, a
      hemodynamic mechanism in 12 of 100 patients, and a mixed mechanism in 3 of 100
      patients. CONCLUSIONS: Stroke in patients with CAD is most frequently associated
      with both direct and indirect signs of artery-to-artery embolization on imaging,
      a finding that should help design future therapeutic trials.

PMID- 22403054
TI  - Aging does not reduce heat shock protein 70 in the absence of chronic insulin
      resistance.
AB  - Heat shock protein (HSP)70 decreases with age. Often aging is associated with
      coincident insulin resistance and higher blood glucose levels, which also
      associate with lower HSP70. We aimed to understand how these factors interrelate
      through a series of experiments using vervet monkeys (Chlorocebus aethiops
      sabaeous). Monkeys (n = 284, 4-25 years) fed low-fat diets showed no association
      of muscle HSP70 with age (r = .04, p = .53), but levels were highly heritable.
      Insulin resistance was induced in vervet monkeys with high-fat diets, and muscle
      biopsies were taken after 0.3 or 6 years. HSP70 levels were significantly greater
      after 0.3 years (+72%, p < .05) but were significantly lower following 6 years of
      high-fat diet (-77%, p < .05). Associations with glucose also switched from being
      positive (r = .44, p = .03) to strikingly negative (r = -.84, p < .001) with
      increasing insulin resistance. In conclusion, a low-fat diet may preserve tissue
      HSP70 and health with aging, whereas high-fat diets, insulin resistance, and
      genetic factors may be more important than age for determining HSP70 levels.

PMID- 22403055
TI  - Brain white matter hyperintensities, executive dysfunction, instability, and
      falls in older people: a prospective cohort study.
AB  - BACKGROUND: White matter hyperintensities (WMHs) are associated with fall risk
      factors in older people including reduced cognitive functioning and impaired
      balance and gait. This prospective study investigated relationships between WMHs,
      sensorimotor performance, executive functioning, and falls in a large sample of
      community-living older people. METHODS: Two hundred and eighty-seven community
      dwelling people aged 70-90 years, underwent structural magnetic resonance imaging
      and assessments of executive function (Trail-Making Tests), sensorimotor
      performance (Physiological Profile Assessment), and prospective monitoring of
      falls. Total WMH volume was quantified using an automated method. Fallers were
      defined as people who had at least one injurious or two noninjurious falls during
      the 12-month follow-up period. RESULTS: Participants with severe WMH burden (WMH
      volumes as a percentage of intracranial volume in the fourth quartile) performed
      poorly in the Trail-Making Test and Physiological Profile Assessment (p < .05)
      and had an increased risk of falls during the 12-month follow-up (relative risk =
      1.63, 95% confidence interval 1.11-2.40). The association between WMHs and falls
      was little changed after adjusting for Trail-Making Test and Physiological
      Profile Assessment scores, age, sex, education, and a range of cardiovascular
      risk factors (relative risk = 1.55, 95% confidence interval 1.06-2.26).
      CONCLUSIONS: Greater WMH burden predicts falls over 12 months, and the
      association between greater burden of WMHs and falls appears to be independent of
      reduced executive function and sensorimotor performance. Strategies to reduce the
      development and progression of WMHs may contribute to future falls prevention in
      older people.

PMID- 22403056
TI  - Elucidating disparities across racial and ethnic groups in multiple myeloma
      patients.

PMID- 22403057
TI  - Botryoid nuclei of neutrophils and monocytes in autoimmune limbic encephalitis.

PMID- 22403058
TI  - Childhood acute myeloid leukemia with bone marrow eosinophilia caused by
      t(16;21)(q24;q22).
AB  - Acute myeloid leukemia with abnormal bone marrow eosinophilia (AML-M4Eo) is often
      reported in core binding factor (CBF) leukemia, with translocations such as
      inv(16)(p13q22), t(16;16)(p13;q22) or t(8;21)(q22;q22); however, it is rarely
      reported with t(16;21)(q24;q22), which produces the RUNX1-CBFA2T3 (AML1-MTG16)
      chimera. The similarity between this chimera and RUNX1-RUNXT1 (AML1-MTG8) by
      t(8;21)(q22;q22) remains controversial. Adult leukemia with t(16;21)(q24;q22) was
      primarily therapy related, and shows poor prognosis; however, pediatric AML with
      this translocation was quite rare and tended to be de novo AML. We present here a
      4-year-old boy with de novo AML-M4Eo and t(16;21)(q24;q22). He received
      chemotherapy and survived for more than 70 months without transplantation. We
      speculated that pediatric AML with t(16;21)(q24;q22) showed favorable prognosis,
      as with t(8;21)(q22;q22).

PMID- 22403059
TI  - Bilateral subdural hemorrhage as a serious adverse event of dasatinib in a
      patient with Philadelphia chromosome-positive acute lymphoblastic leukemia.

PMID- 22403060
TI  - James R. Arnold: from the Manhattan Project to the moon and beyond.

PMID- 22403061
TI  - Endothelial expression of hypoxia-inducible factor 1 protects the murine heart
      and aorta from pressure overload by suppression of TGF-beta signaling.
AB  - Chronic systemic hypertension causes cardiac pressure overload leading to
      increased myocardial O(2) consumption. Hypoxia-inducible factor 1 (HIF-1) is a
      master regulator of O(2) homeostasis. Mouse embryos lacking expression of the
      O(2)-regulated HIF-1alpha subunit die at midgestation with severe cardiac
      malformations and vascular regression. Here we report that Hif1a(f/f);Tie2-Cre
      conditional knockout mice, which lack HIF-1alpha expression only in Tie2(+)
      lineage cells, develop normally, but when subjected to pressure overload induced
      by transaortic constriction (TAC), they manifest rapid cardiac decompensation,
      which is accompanied by excess cardiac fibrosis and myocardial hypertrophy,
      decreased myocardial capillary density, increased myocardial hypoxia and
      apoptosis, and increased TGF-beta signaling through both canonical and
      noncanonical pathways that activate SMAD2/3 and ERK1/2, respectively, within
      endothelial cells of cardiac blood vessels. TAC also induces dilatation of the
      proximal aorta through enhanced TGF-beta signaling in Hif1a(f/f);Tie2-Cre mice.
      Inhibition of TGF-beta signaling by treatment with neutralizing antibody or
      pharmacologic inhibition of MEK-ERK signaling prevented TAC-induced contractile
      dysfunction and pathological remodeling. Thus, HIF-1 plays a critical protective
      role in the adaptation of the heart and aorta to pressure overload by negatively
      regulating TGF-beta signaling in endothelial cells. Treatment of wild-type mice
      with digoxin, which inhibits HIF-1alpha synthesis, resulted in rapid cardiac
      failure after TAC. Although digoxin has been used for decades as an inotropic
      agent to treat heart failure, it does not improve survival, suggesting that the
      countertherapeutic effects of digoxin observed in the TAC mouse model may have
      clinical relevance.

PMID- 22403062
TI  - Antiparallel beta-sheet architecture in Iowa-mutant beta-amyloid fibrils.
AB  - Wild-type, full-length (40- and 42-residue) amyloid beta-peptide (Abeta) fibrils
      have been shown by a variety of magnetic resonance techniques to contain cross
      beta structures in which the beta-sheets have an in-register parallel
      supramolecular organization. In contrast, recent studies of fibrils formed in
      vitro by the Asp23-to-Asn mutant of 40-residue Abeta (D23N-Abeta(1-40)), which is
      associated with early onset neurodegeneration, indicate that D23N-Abeta(1-40)
      fibrils can contain either parallel or antiparallel beta-sheets. We report a
      protocol for producing structurally pure antiparallel D23N-Abeta(1-40) fibril
      samples and a series of solid state nuclear magnetic resonance and electron
      microscopy measurements that lead to a specific model for the antiparallel D23N
      Abeta(1-40) fibril structure. This model reveals how both parallel and
      antiparallel cross-beta structures can be constructed from similar peptide
      monomer conformations and stabilized by similar sets of interactions, primarily
      hydrophobic in nature. We find that antiparallel D23N-Abeta(1-40) fibrils are
      thermodynamically metastable with respect to conversion to parallel structures,
      propagate less efficiently than parallel fibrils in seeded fibril growth, and
      therefore must nucleate more efficiently than parallel fibrils in order to be
      observable. Experiments in neuronal cell cultures indicate that both antiparallel
      and parallel D23N-Abeta(1-40) fibrils are cytotoxic. Thus, our antiparallel D23N
      Abeta(1-40) fibril model represents a specific "toxic intermediate" in the
      aggregation process of a disease-associated Abeta mutant.

PMID- 22403063
TI  - Structure-based model of allostery predicts coupling between distant sites.
AB  - Allostery is a phenomenon that couples effector ligand binding at an allosteric
      site to a structural and/or dynamic change at a distant regulated site. To study
      an allosteric transition, we vary the size of the allosteric site and its
      interactions to construct a series of energy landscapes with pronounced minima
      corresponding to both the effector bound and unbound crystal structures. We use
      molecular dynamics to sample these landscapes. The degree of perturbation by the
      effector, modeled by the size of the allosteric site, provides an order parameter
      for allostery that allows us to determine how microscopic motions give rise to
      commonly discussed macroscopic mechanisms: (i) induced fit, (ii) population
      shift, and (iii) entropy driven. These mechanisms involve decreasing structural
      differences between the effector bound and unbound populations. A metric (ligand
      induced cooperativity) can measure how cooperatively a given regulated site
      responds to effector binding and therefore what kind of allosteric mechanism is
      involved. We apply the model to three proteins with experimentally characterized
      transitions: (i) calmodulin-GFP Ca(2+) sensor protein, (ii) maltose binding
      protein, and (iii) CSL transcription factor. Remarkably, the model is able to
      reproduce allosteric motion and predict coupling in a manner consistent with
      experiment.

PMID- 22403064
TI  - Control of protein signaling using a computationally designed GTPase/GEF
      orthogonal pair.
AB  - Signaling pathways depend on regulatory protein-protein interactions; controlling
      these interactions in cells has important applications for reengineering
      biological functions. As many regulatory proteins are modular, considerable
      progress in engineering signaling circuits has been made by recombining commonly
      occurring domains. Our ability to predictably engineer cellular functions,
      however, is constrained by complex crosstalk observed in naturally occurring
      domains. Here we demonstrate a strategy for improving and simplifying protein
      network engineering: using computational design to create orthogonal (non
      crossreacting) protein-protein interfaces. We validated the design of the
      interface between a key signaling protein, the GTPase Cdc42, and its activator,
      Intersectin, biochemically and by solving the crystal structure of the engineered
      complex. The designed GTPase (orthoCdc42) is activated exclusively by its
      engineered cognate partner (orthoIntersectin), but maintains the ability to
      interface with other GTPase signaling circuit components in vitro. In mammalian
      cells, orthoCdc42 activity can be regulated by orthoIntersectin, but not wild
      type Intersectin, showing that the designed interaction can trigger complex
      processes. Computational design of protein interfaces thus promises to provide
      specific components that facilitate the predictable engineering of cellular
      functions.

PMID- 22403065
TI  - Identification of immunogenic microbial patterns takes the fast lane.

PMID- 22403066
TI  - Intestinal CX3C chemokine receptor 1(high) (CX3CR1(high)) myeloid cells prevent T
      cell-dependent colitis.
AB  - Adequate activation of CD4(+) T lymphocytes is essential for host defense against
      invading pathogens; however, exaggerated activity of effector CD4(+) T cells
      induces tissue damage, leading to inflammatory disorders such as inflammatory
      bowel diseases. Several unique subsets of intestinal innate immune cells have
      been identified. However, the direct involvement of innate immune cell subsets in
      the suppression of T-cell-dependent intestinal inflammation is poorly understood.
      Here, we report that intestinal CX(3)C chemokine receptor 1(high)
      (CX(3)CR1(high)) CD11b(+) CD11c(+) cells are responsible for prevention of
      intestinal inflammation through inhibition of T-cell responses. These cells
      inhibit CD4(+) T-cell proliferation in a cell contact-dependent manner and
      prevent T-cell-dependent colitis. The suppressive activity is abrogated in the
      absence of the IL-10/Stat3 pathway. These cells inhibit T-cell proliferation by
      two steps. Initially, CX(3)CR1(high) CD11b(+) CD11c(+) cells preferentially
      interact with T cells through highly expressed intercellular adhesion molecule
      1/vascular cell adhesion molecule-1; then, they fail to activate T cells because
      of defective expression of CD80/CD86. The IL-10/Stat3 pathway mediates the
      reduction of CD80/CD86 expression. Transfer of wild-type CX(3)CR1(high) CD11b(+)
      CD11c(+) cells prevents development of colitis in myeloid-specific Stat3
      deficient mice. Thus, these cells are regulatory myeloid cells that are
      responsible for maintaining intestinal homeostasis.

PMID- 22403067
TI  - Complex sperm evolution.

PMID- 22403068
TI  - Promiscuous binding of extracellular peptides to cell surface class I MHC
      protein.
AB  - Algorithms derived from measurements of short-peptide (8-10 mers) binding to
      class I MHC proteins suggest that the binding groove of a class I MHC protein,
      such as K(b), can bind well over 1 million different peptides with significant
      affinity (<500 nM), a level of ligand-binding promiscuity approaching the level
      of heat shock protein binding of unfolded proteins. MHC proteins can,
      nevertheless, discriminate between similar peptides and bind many of them with
      high (nanomolar) affinity. Some insights into this high-promiscuity/high-affinity
      behavior and its impact on immunodominant peptides in T-cell responses to some
      infections and vaccination are suggested by results obtained here from testing a
      model developed to predict the number of cell surface peptide-MHC complexes that
      form on cells exposed to extracellular (exogenous) peptides.

PMID- 22403069
TI  - Evaluation of competing J domain:Hsp70 complex models in light of existing
      mutational and NMR data.

PMID- 22403070
TI  - Factors contributing to the high prevalence of multidrug-resistant tuberculosis:
      a study from China.
AB  - BACKGROUND: The rapid spread of multidrug-resistant tuberculosis (MDR-TB) has
      attracted global concerns. This study aimed to identify factors contributing to
      the high prevalence of MDR-TB in China's Heilongjiang province. METHODS: A cross
      sectional survey following the WHO/International Union Against Tuberculosis and
      Lung Disease guidelines was conducted with consecutive recruitment of patients
      with TB in 30 counties selected at random in Heilongjiang in 2004. A total of
      1995 patients were tested for MDR-TB. Factors associated with MDR-TB were
      identified through multilevel models and traditional logistic regression
      analysis, along with in-depth interviews with nine patients, five healthcare
      managers and four doctors. RESULTS: 241 patients (12%) were identified with MDR
      TB. The retreatment patients were 5.48 times (95% CI 4.04 to 7.44) more likely to
      have MDR-TB than newly diagnosed patients. The patients who were treated with
      isoniazid and rifampin for >180 days were 4.82 times (95% CI 2.97 to 7.81) more
      likely to develop MDR-TB than those treated <180 days. Age and delay in
      initiating TB treatment were associated with MDR-TB. Financial burden, poor
      knowledge and side effects of TB treatment were perceived by the interviewees as
      influencing factors. Lack of coordination of services, unsatisfactory supervision
      of treatment and infection control jeopardised the control of MDR-TB.
      CONCLUSIONS: Inappropriate treatment is the most important influencing factor of
      MDR-TB. Increasing people's awareness of TB, early detection and appropriate
      treatment of patients with TB should become a priority, which requires strong
      commitment and collaboration among health organisations and greater compliance
      with TB treatment guidelines by service providers and patients.

PMID- 22403072
TI  - The phosphatidylinositol 4-kinases: don't call it a comeback.
AB  - Phosphatidylinositol 4-phosphate (PtdIns4P) is a quantitatively minor membrane
      phospholipid which is the precursor of PtdIns(4,5)P (2) in the classical agonist
      regulated phospholipase C signalling pathway. However, PtdIns4P also governs the
      recruitment and function of numerous trafficking molecules, principally in the
      Golgi complex. The majority of phosphoinositides (PIs) phosphorylated at the D4
      position of the inositol headgroup are derived from PtdIns4P and play roles in a
      diverse array of fundamental cellular processes including secretion, cell
      migration, apoptosis and mitogenesis; therefore, PtdIns4P biosynthesis can be
      regarded as key point of regulation in many PI-dependent processes.Two
      structurally distinct sequence families, the type II and type III PtdIns 4
      kinases, are responsible for PtdIns4P synthesis in eukaryotic organisms. These
      important proteins are differentially expressed, localised and regulated by
      distinct mechanisms, indicating that the enzymes perform non-redundant roles in
      trafficking and signalling. In recent years, major advances have been made in our
      understanding of PtdIns4K biology and here we summarise current knowledge of
      PtdIns4K structure, function and regulation.

PMID- 22403073
TI  - PIP kinases from the cell membrane to the nucleus.
AB  - Phosphatidylinositol 4,5-bisphosphate (PIP(2)) is a membrane bound lipid molecule
      with capabilities to affect a wide array of signaling pathways to regulate very
      different cellular processes. PIP(2) is used as a precursor to generate the
      second messengers PIP(3), DAG and IP(3), indispensable molecules for signaling
      events generated by membrane receptors. However, PIP(2) can also directly
      regulate a vast array of proteins and is emerging as a crucial messenger with the
      potential to distinctly modulate biological processes critical for both normal
      and pathogenic cell physiology. PIP(2) directly associates with effector proteins
      via unique phosphoinositide binding domains, altering their localization and/or
      enzymatic activity. The spatial and temporal generation of PIP(2) synthesized by
      the phosphatidylinositol phosphate kinases (PIPKs) tightly regulates the
      activation of receptor signaling pathways, endocytosis and vesicle trafficking,
      cell polarity, focal adhesion dynamics, actin assembly and 3' mRNA processing.
      Here we discuss our current understanding of PIPKs in the regulation of cellular
      processes from the plasma membrane to the nucleus.

PMID- 22403075
TI  - Phosphoinositide 3-kinases-a historical perspective.
AB  - The phosphoinositide 3-kinase (PI 3-K) signal relay pathway represents arguably
      one of the most intensely studied mechanisms by which extracellular signals
      elicit cellular responses through the generation of second messengers that are
      associated with cell growth and transformation. This chapter reviews the many
      landmark discoveries in the PI 3-K signaling pathway in biology and disease, from
      the identification of a novel phosphoinositide kinase activity associated with
      transforming oncogenes in the 1980s, to the identification of oncogenic mutations
      in the catalytic subunit of PI 3-K in the mid 2000s. Two and a half decades of
      intense research have provided clear evidence that the PI 3-K pathway controls
      virtually all aspects of normal cellular physiology, and that deregulation of one
      or more proteins that regulate or transduce the PI 3-K signal ultimately leads to
      human pathology. The most recent efforts have focused on the development of
      specific PI 3-K inhibitors that are currently being evaluated in clinical trials
      for a range of disease states.This chapter is devoted to a historical review of
      the landmark findings in the PI 3-K from its relatively humble beginnings in the
      early to mid 1980s up until the present day. When considering the key findings in
      the history of PI 3-K, it is essential to recognize the landmark studies by
      Lowell and Mabel Hokin in the 1950s who were the first to describe that
      extracellular agonists such as acetylcholine could stimulate the incorporation of
      radiolabeled phosphate into phospholipids (Hokin and Hokin 1953). Their work
      initiated an entirely new field of lipid signaling, and subsequent studies in the
      1970s by Michell and Lapetina who linked phosphoinositide turnover to membrane
      associated receptors that initiate intracellular calcium mobilization (Lapetina
      and Michell 1973). Later studies revealed that the phospholipase-mediated
      breakdown of the same minor membrane phospholipids such as PtdIns-4,5-P(2)
      (phosphatidylinositol-4,5-bisphosphate) is responsible for the release of two
      additional key second messengers, diacylglycerol (DG) and IP(3) (inositol-1,4,5
      trisphosphate) (Kirk et al. 1981; Berridge 1983; Berridge et al. 1983). Berridge,
      Irvine and Schulz then revealed that one of the byproducts of this lipid signal
      relay pathway is the release of calcium from intracellular stores such as the
      endoplasmic reticulum (Streb et al. 1983). Finally, pioneering studies by
      Nishizuka in the late 1970s identified PKC (protein kinase C) as a phospholipid
      and diacylglycerol-activated serine/threonine protein kinase (Inoue et al. 1977;
      Takai et al. 1977). At this point, it probably seemed to most at the time that
      the story was complete, such that hydrolysis of phosphoinositides such as PtdIns
      4,5-P(2) and PtdIns-4-P would account for the major mechanisms of agonist
      stimulated lipid signaling leading to physiological responses. On the contrary,
      the story was far from complete and was about to become a lot more complex.

PMID- 22403076
TI  - PI3Ks-drug targets in inflammation and cancer.
AB  - Phosphoinositide 3-kinases (PI3Ks) control cell growth, proliferation, cell
      survival, metabolic activity, vesicular trafficking, degranulation, and
      migration. Through these processes, PI3Ks modulate vital physiology. When over
      activated in disease, PI3K promotes tumor growth, angiogenesis, metastasis or
      excessive immune cell activation in inflammation, allergy and autoimmunity. This
      chapter will introduce molecular activation and signaling of PI3Ks, and
      connections to target of rapamycin (TOR) and PI3K-related protein kinases
      (PIKKs). The focus will be on class I PI3Ks, and extend into current developments
      to exploit mechanistic knowledge for therapy.

PMID- 22403074
TI  - The phospholipase C isozymes and their regulation.
AB  - The physiological effects of many extracellular neurotransmitters, hormones,
      growth factors, and other stimuli are mediated by receptor-promoted activation of
      phospholipase C (PLC) and consequential activation of inositol lipid signaling
      pathways. These signaling responses include the classically described conversion
      of phosphatidylinositol(4,5)P(2) to the Ca(2+)-mobilizing second messenger
      inositol(1,4,5)P(3) and the protein kinase C-activating second messenger
      diacylglycerol as well as alterations in membrane association or activity of many
      proteins that harbor phosphoinositide binding domains. The 13 mammalian PLCs
      elaborate a minimal catalytic core typified by PLC-d to confer multiple modes of
      regulation of lipase activity. PLC-b isozymes are activated by Gaq- and Gbg
      subunits of heterotrimeric G proteins, and activation of PLC-g isozymes occurs
      through phosphorylation promoted by receptor and non-receptor tyrosine kinases.
      PLC-e and certain members of the PLC-b and PLC-g subclasses of isozymes are
      activated by direct binding of small G proteins of the Ras, Rho, and Rac
      subfamilies of GTPases. Recent high resolution three dimensional structures
      together with biochemical studies have illustrated that the X/Y linker region of
      the catalytic core mediates autoinhibition of most if not all PLC isozymes.
      Activation occurs as a consequence of removal of this autoinhibition.

PMID- 22403077
TI  - Phosphoinositide 3-kinases in health and disease.
AB  - In the last decade, the availability of genetically modified animals has revealed
      interesting roles for phosphoinositide 3-kinases (PI3Ks) as signaling platforms
      orchestrating multiple cellular responses, both in health and pathology. By
      acting downstream distinct receptor types, PI3Ks nucleate complex signaling
      assemblies controlling several biological process, ranging from cell
      proliferation and survival to immunity, cancer, metabolism and cardiovascular
      control. While the involvement of these kinases in modulating immune reactions
      and neoplastic transformation has long been accepted, recent progress from our
      group and others has highlighted new and unforeseen roles of PI3Ks in controlling
      cardiovascular function. Hence, the view is emerging that pharmacological
      targeting of distinct PI3K isoforms could be successful in treating disorders
      such as myocardial infarction and heart failure, besides inflammatory diseases
      and cancer. Currently, PI3Ks represent attractive drug targets for companies
      interested in the development of novel and safe treatments for such diseases.
      Numerous hit and lead compounds are now becoming available and, for some of them,
      clinical trials can be envisaged in the near future. In the following sections,
      we will outline the impact of specific PI3K isoforms in regulating different
      cellular contexts, including immunity, metabolism, cancer and cardiovascular
      system, both in physiological and disease conditions.

PMID- 22403078
TI  - Phosphoinositide phosphatases: just as important as the kinases.
AB  - Phosphoinositide phosphatases comprise several large enzyme families with over 35
      mammalian enzymes identified to date that degrade many phosphoinositide signals.
      Growth factor or insulin stimulation activates the phosphoinositide 3-kinase that
      phosphorylates phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P(2)] to form
      phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P(3)], which is rapidly
      dephosphorylated either by PTEN (phosphatase and tensin homologue deleted on
      chromosome 10) to PtdIns(4,5)P(2), or by the 5-phosphatases (inositol
      polyphosphate 5-phosphatases), generating PtdIns(3,4)P(2). 5-phosphatases also
      hydrolyze PtdIns(4,5)P(2) forming PtdIns(4)P. Ten mammalian 5-phosphatases have
      been identified, which regulate hematopoietic cell proliferation, synaptic
      vesicle recycling, insulin signaling, and embryonic development. Two 5
      phosphatase genes, OCRL and INPP5E are mutated in Lowe and Joubert syndrome
      respectively. SHIP [SH2 (Src homology 2)-domain inositol phosphatase] 2, and SKIP
      (skeletal muscle- and kidney-enriched inositol phosphatase) negatively regulate
      insulin signaling and glucose homeostasis. SHIP2 polymorphisms are associated
      with a predisposition to insulin resistance. SHIP1 controls hematopoietic cell
      proliferation and is mutated in some leukemias. The inositol polyphosphate 4
      phosphatases, INPP4A and INPP4B degrade PtdIns(3,4)P(2) to PtdIns(3)P and
      regulate neuroexcitatory cell death, or act as a tumor suppressor in breast
      cancer respectively. The Sac phosphatases degrade multiple phosphoinositides,
      such as PtdIns(3)P, PtdIns(4)P, PtdIns(5)P and PtdIns(3,5)P(2) to form PtdIns.
      Mutation in the Sac phosphatase gene, FIG4, leads to a degenerative neuropathy.
      Therefore the phosphatases, like the lipid kinases, play major roles in
      regulating cellular functions and their mutation or altered expression leads to
      many human diseases.

PMID- 22403079
TI  - The PTEN and Myotubularin phosphoinositide 3-phosphatases: linking lipid
      signalling to human disease.
AB  - Two classes of lipid phosphatases selectively dephosphorylate the 3 position of
      the inositol ring of phosphoinositide signaling molecules: the PTEN and the
      Myotubularin families. PTEN dephosphorylates PtdIns(3,4,5)P(3), acting in direct
      opposition to the Class I PI3K enzymes in the regulation of cell growth,
      proliferation and polarity and is an important tumor suppressor. Although there
      are several PTEN-related proteins encoded by the human genome, none of these
      appear to fulfill the same functions. In contrast, the Myotubularins
      dephosphorylate both PtdIns(3)P and PtdIns(3,5)P(2), making them antagonists of
      the Class II and Class III PI 3-kinases and regulators of membrane traffic. Both
      phosphatase groups were originally identified through their causal mutation in
      human disease. Mutations in specific myotubularins result in myotubular myopathy
      and Charcot-Marie-Tooth peripheral neuropathy; and loss of PTEN function through
      mutation and other mechanisms is evident in as many as a third of all human
      tumors. This chapter will discuss these two classes of phosphatases, covering
      what is known about their biochemistry, their functions at the cellular and whole
      body level and their influence on human health.

PMID- 22403080
TI  - Computer-aided detection system performance on current and previous digital
      mammograms in patients with contralateral metachronous breast cancer.
AB  - BACKGROUND: The computer-aided detection (CAD) system is widely used for
      screening mammography. The performance of the CAD system for contralateral breast
      cancer has not been reported for women with a history of breast cancer. PURPOSE:
      To retrospectively evaluate the performance of a CAD system on current and
      previous mammograms in patients with contralateral metachronous breast cancer.
      MATERIAL AND METHODS: During a 3-year period, 4945 postoperative patients had
      follow-up examinations, from whom we selected 55 women with contralateral breast
      cancers. Among them, 38 had visible malignant signs on the current mammograms. We
      analyzed the sensitivity and false-positive marks of the system on the current
      and previous mammograms according to lesion type and breast density. RESULTS: The
      total visible lesion components on the current mammograms included 27 masses and
      14 calcifications in 38 patients. The case-based sensitivity for all lesion types
      was 63.2% (24/38) with false-positive marks of 0.71 per patient. The lesion-based
      sensitivity for masses and calcifications was 59.3% (16/27) and 71.4% (10/14),
      respectively. The lesion-based sensitivity for masses in fatty and dense breasts
      was 68.8% (11/16) and 45.5% (5/11), respectively. The lesion-based sensitivity
      for calcifications in fatty and dense breasts was 100.0% (3/3) and 63.6% (7/11),
      respectively. The total visible lesion components on the previous mammograms
      included 13 masses and three calcifications in 16 patients, and the sensitivity
      for all lesion types was 31.3% (5/16) with false-positive marks of 0.81 per
      patient. On these mammograms, the sensitivity for masses and calcifications was
      30.8% (4/13) and 33.3% (1/3), respectively. The sensitivity in fatty and dense
      breasts was 28.6% (2/7) and 33.3% (3/9), respectively. CONCLUSION: In the women
      with a history of breast cancer, the sensitivity of the CAD system in visible
      contralateral breast cancer was lower than in most previous reports using the
      same CAD system probably due to the relatively small size, subtlety of the lesion
      findings, and dense parenchymal pattern.

PMID- 22403081
TI  - Clinical outcomes after percutaneous biliary interventions in patients with
      malignant biliary obstruction caused by metastatic gastric cancer.
AB  - BACKGROUND: No report has appeared on the histologic characteristics as
      influencing factors associated with clinical outcomes and survival of patients
      who underwent percutaneous biliary interventions to treat malignant biliary
      obstruction caused by metastatic gastric cancer. PURPOSE: To investigate the
      clinical outcomes after percutaneous biliary interventions in patients with
      malignant biliary obstruction caused by metastatic gastric cancer and to identify
      prognostic factors associated with clinical outcomes. MATERIAL AND METHODS: We
      retrospectively assessed 117 patients who underwent percutaneous transhepatic
      biliary drainage (PTBD) between January 2005 and December 2009, for treatment of
      malignant biliary obstructions caused by metastatic gastric cancer. Of these 117
      patients, 54 subsequently underwent metallic stent placement. RESULTS: The
      technical success rates of PTBD and metallic stent placement were 100% and 100%,
      respectively. Self-limiting hemobilia after PTBD occurred in eight (7%) patients,
      and self-limiting hemobilia (n = 4) and acute pancreatitis (n = 3) after stent
      placement occurred in seven (13%) patients. Successful drainage was achieved in
      105 (90%) of the 117 patients who underwent PTBD and in 49 (91%) of 54 patients
      who underwent metallic stent placement. Multiple Cox's regression analysis showed
      that the histology of primary gastric cancer (P = 0.011), serum bilirubin after
      PTBD (P = 0.002) and stenting (P = 0.017), and chemotherapy after PTBD (P <
      0.001) and stenting (P = 0.033) were independent predictors of survival.
      CONCLUSION: PTBD and subsequent metallic stent placement were safe and effective
      methods for palliative treatment in patients with malignant biliary obstruction
      caused by metastatic gastric cancer. Patients with a differentiated histology of
      primary gastric cancer and serum bilirubin level <=2 mg/dl after PTBD are
      probably the best candidates for treatment with a combination of metallic stent
      placement and chemotherapy.

PMID- 22403082
TI  - Transcatheter renal artery embolization with N-butyl cyanoacrylate.
AB  - BACKGROUND: Despite its long history, the application of N-butyl cyanoacrylate
      (NBCA) has been limited compared to other materials such as particulate agents
      and coils. This possibly owes to a widespread misconception that NBCA is
      difficult to handle and carries a high risk of complications due to its liquid
      nature and rapid polymerization time. However, recent reports have shown that,
      with knowledge and experience, NBCA is safe and effective to use in visceral
      arteries. PURPOSE: To review the outcome of transcatheter embolization of the
      renal artery using NBCA for varied etiologies in the kidney. MATERIAL AND
      METHODS: Fourteen patients with varied etiologies in the kidney underwent renal
      artery embolization using NBCA as the sole embolic agent (64%) or in combination
      with an additional embolic material (36%). A review of medical charts and images
      were performed to gather information regarding underlying etiologies, clinical
      presentation, and outcome of embolization. RESULTS: Technical success was
      achieved in all patients (100%) while clinical success was achieved in 12
      (85.7%). One failed case was managed by repeat embolization using microcoils,
      while the other underwent partial nephrectomy after failed reattempt at
      embolization. Three patients with recurrent bleeding after previously having
      undergone embolization using microcoils or gelatin sponge particles were
      successfully managed the second time using NBCA. NBCA embolization was also
      effective in three patients with hemostatic abnormality. Complications
      attributable to NBCA embolization were renal atrophy in one patient and
      microcatheter tip fracture in another. CONCLUSION: The application of NBCA for
      transcatheter embolization of varied etiologies involving the renal artery is
      feasible and safe in the hands of an experienced interventional radiologist. It
      offers immediate and effective occlusion of the pathologic vessel and, while it
      can be used exclusively on its own, it can also be used to complement other
      embolic materials.

PMID- 22403083
TI  - Informed consent for record linkage: a systematic review.
AB  - BACKGROUND: Record linkage is a useful tool for health research. Potential
      benefits aside, its use raises discussions on privacy issues, such as whether a
      written informed consent for access to health records and linkage should be
      obtained. The authors aim to systematically review studies that assess consent
      proportions to record linkage. METHODS: 8 databases were searched up to June 2011
      to find articles which presented consent proportions to record linkage. The
      screening, eligibility and inclusion of articles were conducted by two
      independent reviewers. The authors carried out meta-regression, subgroup and
      sensitivity analyses to assess heterogeneity. RESULTS: Of the 141 studies
      identified, only 11 presented empirical consent proportions and were included in
      the systematic review. The consent proportion varied widely from 39% to 97%.
      Seven studies presented consent proportions of 88% or higher, one of 72%, and
      only three presented consented proportion equal to or lower than 53%. None of the
      studies' characteristics evaluated explained heterogeneity. CONCLUSION: The
      results of this review show that, in general, individuals tend to consent to the
      use of their data for record linkage, with exceptions in specific populations or
      minorities. The authors believe that this, as well as the cited literature, lends
      support to policies that, while keeping relevant ethical controls in place, do
      not require individual informed consent for each and every study that relies on
      secondary data.

PMID- 22403084
TI  - Predictive genetic testing in minors for late-onset conditions: a chronological
      and analytical review of the ethical arguments.
AB  - Predictive genetic testing is now routinely offered to asymptomatic adults at
      risk for genetic disease. However, testing of minors at risk for adult-onset
      conditions, where no treatment or preventive intervention exists, has evoked
      greater controversy and inspired a debate spanning two decades. This review aims
      to provide a detailed longitudinal analysis and concludes by examining the
      debate's current status and prospects for the future. Fifty-three relevant
      theoretical papers published between 1990 and December 2010 were identified, and
      interpretative content analysis was employed to catalogue discrete arguments
      within these papers. Novel conclusions were drawn from this review. While the
      debate's first voices were raised in opposition of testing and their arguments
      have retained currency over many years, arguments in favour of testing, which
      appeared sporadically at first, have gained momentum more recently. Most
      arguments on both sides are testable empirical claims, so far untested, rather
      than abstract ethical or philosophical positions. The dispute, therein, lies not
      so much in whether minors should be permitted to access predictive genetic
      testing but whether these empirical claims on the relative benefits or harms of
      testing should be assessed.

PMID- 22403086
TI  - Myocardial infarction and generalised anxiety disorder: 10-year follow-up.
AB  - BACKGROUND: Few studies have addressed the relationship between generalised
      anxiety disorder and cardiovascular prognosis using a diagnostic interview. AIMS:
      To assess the association between generalised anxiety disorder and adverse
      outcomes in patients with myocardial infarction. METHOD: Patients with acute
      myocardial infarction (n = 438) were recruited between 1997 and 2000 and were
      followed up until 2007. Current generalised anxiety disorder and post-myocardial
      infarction depression were assessed with the Composite International Diagnostic
      Interview. The end-point consisted of all-cause mortality and cardiovascular
      related readmissions. RESULTS: During the follow-up period, 198 patients had an
      adverse event. Generalised anxiety disorder was associated with an increased rate
      of adverse events after adjustment for age and gender (hazard ratio: 1.94; 95%
      confidence interval: 1.14-3.30; P = 0.01). Additional adjustment for measures of
      cardiac disease severity and depression did not change the results. CONCLUSIONS:
      Generalised anxiety disorder was associated with an almost twofold increased risk
      of adverse outcomes independent demographic and clinical variables and
      depression.

PMID- 22403085
TI  - Parent psychopathology and offspring mental disorders: results from the WHO World
      Mental Health Surveys.
AB  - BACKGROUND: Associations between specific parent and offspring mental disorders
      are likely to have been overestimated in studies that have failed to control for
      parent comorbidity. AIMS: To examine the associations of parent with respondent
      disorders. METHOD: Data come from the World Health Organization (WHO) World
      Mental Health Surveys (n = 51 507). Respondent disorders were assessed with the
      Composite International Diagnostic Interview and parent disorders with informant
      based Family History Research Diagnostic Criteria interviews. RESULTS: Although
      virtually all parent disorders examined (major depressive, generalised anxiety,
      panic, substance and antisocial behaviour disorders and suicidality) were
      significantly associated with offspring disorders in multivariate analyses,
      little specificity was found. Comorbid parent disorders had significant sub
      additive associations with offspring disorders. Population-attributable risk
      proportions for parent disorders were 12.4% across all offspring disorders,
      generally higher in high- and upper-middle- than low-/lower-middle-income
      countries, and consistently higher for behaviour (11.0-19.9%) than other (7.1
      14.0%) disorders. CONCLUSIONS: Parent psychopathology is a robust non-specific
      predictor associated with a substantial proportion of offspring disorders.

PMID- 22403087
TI  - Use of second-person pronouns and schizophrenia.
AB  - A masked analysis of videotaped assessments of people at high genetic risk of
      schizophrenia revealed that those who subsequently went on to develop
      schizophrenia used significantly more second-person pronouns. This was evident
      before diagnosis, at two separate assessments approximately 18 months apart. This
      supports the view that people who go on to develop schizophrenia may have an
      abnormality in the deictic frame of interpersonal communication - that is, the
      distinction between concepts being self-generated or from elsewhere may be
      blurred prior to the onset of a diagnosis of schizophrenia.

PMID- 22403088
TI  - Suicide and non-suicide mortality after self-harm in Taipei City, Taiwan.
AB  - BACKGROUND: Most previous studies of long-term mortality risk following self-harm
      have been conducted in Western countries with few studies from Asia. AIMS: To
      investigate suicide and non-suicide mortality after non-fatal self-harm in Taipei
      City, Taiwan. METHOD: Prospective cohort study (median follow-up 3.3 years) of
      7601 individuals presenting to hospital with self-harm (January 2004 to December
      2006). Standardised mortality ratios (SMRs) for suicide and non-suicide mortality
      were calculated. RESULTS: Suicide risk in the year following self-harm was over
      100 times higher than in the general population (SMR = 119.6, 95% CI 99.6-142.5).
      Males and middle-aged and older adults had the highest subsequent risk of
      suicide. Compared with people who took an overdose, individuals who used hanging
      or charcoal burning in their index episode had the highest risk of suicide. For
      non-suicide mortality the SMRs were 6.7 (95% CI 5.7-7.8) in the first year and
      4.4 (95% CI 3.9-4.9) during the whole follow-up period. CONCLUSIONS: Patterns of
      increased all-cause and suicide mortality following an episode of self-harm are
      similar in Taipei City to those seen in Western countries. Designing better
      aftercare following non-fatal self-harm, particularly for those with underlying
      physical disorders or who have used lethal self-harm methods, should be a
      priority for suicide prevention programmes in Asia.

PMID- 22403089
TI  - Distinguishing adolescents who think about self-harm from those who engage in
      self-harm.
AB  - BACKGROUND: Adolescent self-harm is a major public health concern, yet little is
      known about the factors that distinguish adolescents who think about self-harm
      but do not act on these thoughts from those who act on such thoughts. AIMS:
      Within a new theoretical model, the integrated motivational-volitional model, we
      investigated factors associated with adolescents having thoughts of self-harm
      (ideators) v. those associated with self-harm enaction (enactors). METHOD:
      Observational study of school pupils employing an anonymous self-report survey to
      compare three groups of adolescents: self-harm enactors (n = 628) v. self-harm
      ideators (n = 675) v. those without any self-harm history (n = 4219). RESULTS:
      Enactors differed from ideators on all of the volitional factors. Relative to
      ideators, enactors were more likely to have a family member/close friend who had
      self-harmed, more likely to think that their peers engaged in self-harm and they
      were more impulsive than the ideators. Enactors also reported more life stress
      than ideators. Conversely, the two self-harm groups did not differ on any of the
      variables associated with the development of self-harm thoughts. CONCLUSIONS: As
      more adolescents think about self-harm than engage in it, a better understanding
      of the factors that govern behavioural enaction is crucial in the effective
      assessment of the risk of self-harm.

PMID- 22403090
TI  - Using sympathetic skin responses in individuals with spinal cord injury as a
      quantitative evaluation of motor imagery abilities.
AB  - BACKGROUND: Motor imagery (MI) ability should be evaluated in selected
      individuals with spinal cord injury (SCI) who can benefit from MI training in
      their rehabilitation program. Electrodermal activity seems to be a reliable
      indicator for assessing MI ability. However, individuals with SCI have a variety
      of autonomic dysfunctions. OBJECTIVE: This study aimed to investigate
      electrodermal responses (EDRs) elicited by MI. DESIGN: A cost-utility analysis of
      EDR above and below the lesion level in individuals with complete or incomplete
      SCI (n = 30) versus a control group of individuals who were healthy (n = 10) was
      used. METHOD: The EDR was recorded above and below the lesion level during MI of
      a drinking action. Duration, latency, and amplitude of EDR were the outcome
      measures. RESULTS: Hand and foot EDR in the control group occurred with the same
      pattern and similar latencies, suggesting a common efferent sympathetic pathway
      to sweat glands of the hand and foot mediating a sympathetic skin response.
      Individuals with SCI elicited responses above the lesion level. The EDR amplitude
      was correlated to the lesion level and autonomic dysreflexia history. No foot
      response was recorded in individuals with complete cervical and thoracic motor
      lesions. Foot response with a lower amplitude and higher latency occurred in
      participants with incomplete motor lesion, suggesting a link between the
      descending motor pathway and sympathetic function. LIMITATIONS: The small sample
      of individuals with incomplete SCI limits the generalization of the results
      obtained at the foot site. CONCLUSIONS: Electrodermal response above the lesion
      level may be a reliable index for assessing MI ability in individuals with SCI.
      It is a noninvasive, user-friendly method for clinicians to consider before
      enrolling individuals in MI training.

PMID- 22403091
TI  - Quantitative paraspinal muscle measurements: inter-software reliability and
      agreement using OsiriX and ImageJ.
AB  - BACKGROUND: Variations in paraspinal muscle cross-sectional area (CSA) and
      composition, particularly of the multifidus muscle, have been of interest with
      respect to risk of, and recovery from, low back pain problems. Several
      investigators have reported on the reliability of such muscle measurements using
      various protocols and image analysis programs. However, there is no standard
      protocol for tissue segmentation, nor has there been an investigation of
      reliability or agreement of measurements using different software. OBJECTIVE: The
      purpose of this study was to provide a detailed muscle measurement protocol and
      determine the reliability and agreement of associated paraspinal muscle
      composition measurements obtained with 2 commonly used image analysis programs:
      OsiriX and ImageJ. DESIGN: This was a measurement reliability study. METHODS:
      Lumbar magnetic resonance images of 30 individuals were randomly selected from a
      cohort of patients with various low back conditions. Muscle CSA and composition
      measurements were acquired from axial T2-weighted magnetic resonance images of
      the multifidus muscle, the erector spinae muscle, and the 2 muscles combined at
      L4-L5 and S1 for each participant. All measurements were repeated twice using
      each software program, at least 5 days apart. The assessor was blinded to all
      earlier measurements. RESULTS: The intrarater reliability and standard error of
      measurement (SEM) were comparable for most measurements obtained using OsiriX or
      ImageJ, with reliability coefficients (intraclass correlation coefficients
      [ICCs]) varying between .77 and .99 for OsiriX and .78 and .99 for ImageJ. There
      was similarly excellent agreement between muscle composition measurements using
      the 2 software applications (inter-software ICCs = .81-.99). LIMITATIONS: The
      high degree of inter-software measurement reliability may not generalize to
      protocols using other commercial or custom-made software. CONCLUSION: The
      proposed method to investigate paraspinal muscle CSA, composition, and side-to
      side asymmetry was highly reliable, with excellent agreement between the 2
      software programs.

PMID- 22403092
TI  - Validation of the comprehensive ICF core set for multiple sclerosis from the
      perspective of physical therapists.
AB  - BACKGROUND: The Comprehensive ICF Core Set for Multiple Sclerosis (MS) is an
      application of the International Classification of Functioning, Disability and
      Health (ICF) and represents the typical spectrum of problems in the functioning
      of people with MS. OBJECTIVES: The objective of this study was to validate the
      Comprehensive ICF Core Set for MS from the perspective of physical therapists.
      DESIGN: A 3-round survey based on the Delphi technique was used. METHODS:
      Physical therapists experienced in the management of MS were asked about problems
      and resources of people with MS as well as environmental aspects treated by
      physical therapists (eg, use of assistive devices, support). Statements were
      linked to the ICF and compared with the Comprehensive ICF Core Set for MS.
      RESULTS: Eighty physical therapists from 23 countries mentioned 2,133 issues that
      covered all of the ICF components. Two hundred thirty-eight ICF categories were
      linked to the statements. Forty-six categories in the Comprehensive ICF Core Set
      for MS were confirmed by physical therapists at the same level or a more specific
      level of classification. Nineteen additional ICF categories were reported by at
      least 75% of the participants. CONCLUSIONS: The results of this study support the
      content and face validity of the Comprehensive ICF Core Set for MS. Areas of
      functioning and health that physical therapists believe should be assessed were
      identified. The findings of this study as well as the results of completed and
      ongoing validation studies will further elucidate the validity of the
      Comprehensive ICF Core Set for MS from different perspectives.

PMID- 22403093
TI  - Nil per os except medications order in the dysphagic patient.
AB  - OBJECTIVES: To demonstrate why the 'nil per os except medications' order is
      contraindicated prior to dysphagia testing and to recommend ways to prevent
      aspiration of medications in the dysphagic population. METHODS: A 71-year-old
      male deemed at-risk for aspiration due to coughing when drinking thin liquids was
      made nil per os except medications and referred for dysphagia testing. Swallowing
      was analyzed objectively with trans-nasal fiberoptic endoscopic evaluation of
      swallowing. RESULTS: Aspiration on the initial 5 cc puree bolus swallow trial
      elicited a cough reflex. A 325 mg, 1 cm diameter, enteric coated aspirin pill
      emerged from the trachea, progressed through the glottis and remained transiently
      in the laryngeal vestibule before lodging, along with pudding residue, in a
      mucosal fold of the left vallecula. Neither volitional coughing nor single 5 cc
      water bolus swallows dislodged the pill. Otolaryngology was called and removed
      the pill trans-orally under direct visualization with a Kelly clamp. The pill
      maintained both its enteric coating and integrity for a total of 7.5 h after
      being aspirated. CONCLUSION: The nil per os except medications order is
      contraindicated in the dysphagic population. When aspiration is suspected, nil
      per os including medications is recommended until dysphagia testing determines
      what form of medication can be swallowed safely.

PMID- 22403094
TI  - Photo quiz. A 32-year-old man with ulcerative mucositis, skin lesions, and nail
      dystrophy. Chronic mucocutaneous candidiasis by multidrug-resistant Candida
      albicans.

PMID- 22403105
TI  - Crossing borders: one world, global health: CDC updates recommendations for
      typhoid vaccination.

PMID- 22403106
TI  - [Epidemiology and burden of osteoporosis in Switzerland].
AB  - With increasing life expectancy and a growing proportion of elderly in the Swiss
      population, the burden of osteoporosis increases continuously. Every other woman
      and every fifth man aged 50 years or older will suffer an osteoportic fracture
      during her or his remaining lifetime. While the absolute number of
      hospitalizations for hip fractures has stabilized between year 2000 and 2007, the
      total number of hospitalizations for osteoporotic fractures has increased to
      16'200 (+ 16 %) and 5'600 (+ 20 %) in women and men, respectively. Thus,
      osteoporosis continues belonging to those chronic diseases imposing the highest
      economic burden to the Swiss healthcare system, trend increasing. In addition,
      the risk of subsequent fractures as well as the adjusted mortality risk increases
      significantly after a first osteoporotic fracture. Should appropriate measures
      not be implemented in the near future, so will osteoporosis become one of the key
      challenges for the Swiss healthcare system within the coming years.

PMID- 22403107
TI  - [Osteoporosis: evaluation, diagnosis and monitoring].
AB  - A paradigm change is taking place in the diagnosis of osteoporosis - away from
      the overemphasis on bone mineral density (BMD) as the sole gauge of need for
      diagnosis and treatment towards a comprehensive risk assessment of all the
      components of increased bone fragility. The main risk factors, and thereby
      reasons for further diagnostics, are previous non-traumatic vertebral and non
      vertebral fractures, long-term glucocorticoid therapy, low body weight, increased
      risk of fall, and disorders associated with an increased fracture risk. The
      indication for osteoporosis therapy is based on the individual fracture risk and
      should not be based purely on a single BMD value. Monitoring the effectiveness of
      osteoporosis treatment presents a challenge in everyday clinical practice. As an
      alternative to fracture incidence, surrogate markers (BMD, biochemical markers of
      bone turnover) can be used to assess effectiveness of treatment in the individual
      patient. Correct employment and interpretation of surrogate markers in
      osteoporosis therapy requires knowledge of pre-analytical and analytical factors
      which co-determine the measurement methods. The purpose of this overview is to
      examine the possibilities of clinical investigation, BMD measurement and
      determination of bone turnover markers for the evaluation of therapeutic
      response.

PMID- 22403108
TI  - [Calcium and Vitamin D in the treatment and prevention of osteoporosis: the
      actual dilemma].
AB  - Calcium lowers the fracture risk when given together with vitamin D. In many
      patients the Calcium intake is lower than the recommended amount, because the
      mean value reported in several studies corresponds just to the recommended
      intake, which means that half of the population is below. The American Institute
      of Medicine (IOM) recommends 1200 mg per day. But 1000 mg should be enough in the
      presence of vitamin D sufficieny, particularly because 800 mg are the lowest
      limit for avoiding bone loss. In general, higher doses are harmless. When the
      Calcium intake ca not be increased by nutrition, supplements are indicated. It is
      not proven that they increase the cardiovascular risk, which anyway was not
      reported in the combination with vitamin D, neither with nutritional Calcium.
      Therefore, Calcium hast to be prescribed in the treatment of osteoporosis, after
      meal. Vitamin D too is deficient in most of the patients with osteoporosis,
      especially in advanced age, and should be prescribed together with Calcium,
      because it hardly can be delivered by food. Although there is no toxicity up to
      10'000 IU par day, the IOM proposes only 600 IU per day, and by that neglects the
      fact that this dose hardly leads to a blood level of 25-OH vitamin D which goes
      along with lower fracture risk, and wich leaves a large part of the patients
      vitamin D deficient, unfit for optimal reaction to treatment. Swiss, German and
      American specialists too recommend 800 - 2000 IU per day.

PMID- 22403109
TI  - [Selective Estrogen Receptor Modulators (SERMs) for prevention and treatment of
      postmenopausal osteoporosis].
AB  - The three modern Selective Estrogen Receptor Modulators (SERMs) Raloxifene,
      Lasoxifene and Bazedoxifene registered in Europe reduce in postmenopausal women
      with a high risk for osteoporosis the incidence of vertebral fractures by 30 - 50
      %, depending on the subgroup they belong to. Solid prospective fracture data for
      risk reduction in non-vertebral fractures, including the hip, are missing for
      Raloxifene and Bazedoxifene. However, a post hoc analysis suggests that the risk
      for non-vertebral fractures is significantly reduced by Raloxfene in women with
      severe osteoporosis. The simultaneous decrease of the incidence of ER-positive
      invasive breast cancer in Raloxifene users is highly relevant for clinicians.
      Unfortunately, Raloxifene and Bazedoxifene are, in the EU and in Switzerland,
      only labelled for the use in the prevention and treatment of postmenopausal
      osteoporosis. SERMs may induce or augment vasomotor symptoms. Therefore, SERMs
      are not a first line therapy in early postmenopause. Looking at other hormonal
      options, Hormone Replacement Therapy (HRT) remains the first line therapy for
      fracture reduction in the peri- and early postmenopause. SERMs are an appropriate
      choice for the continuation of fracture prevention after an initial HRT,
      particularly for the prevention of vertebral fractures. SERMs are safe if (as in
      oral HRT) the slightly increased risk for venous thrombo-embolism is respected.
      In conclusion, SERMs have today their well established place in the prevention
      and treatment of postmenopausal osteoporosis, particularly in women with a
      simultaneously increased breast cancer risk.

PMID- 22403110
TI  - [Bisphosphonates treatment in patients with osteoporosis].
AB  - The primary goal of treatment for postmenopausal osteoporosis is the reduction in
      fracture risk. Bisphosphonates have long been established as first-line therapy
      for osteoporosis and several of these drugs significantly reduce osteoporotic
      fracture risk. Alendronate, risedronate, ibandronate and zoledronic acid all
      provide fracture protection for patients with postmenopausal osteoporosis. All
      four agents have demonstrated efficacy in preventing vertebral fractures, but
      only zoledronic acid and risedronate significantly reduce non-vertebral fracture
      risk in pivotal trials. Moreover, reduction in hip fracture risk has been
      established for alendronate, risedronate and zoledronic acid. Ibandronate and
      zoledronic acid have the most persistent antifracture effect. Bisphosphonates
      have been associated with a number of side effects, with a well-documented
      association between gastrointestinal adverse events and oral administration, and
      between acute phase reactions and intravenous administration.

PMID- 22403111
TI  - [Treatment of osteoporosis with Denosumab].
AB  - Denosumab is the first human monoclonal antibody for the treatment of
      osteoporosis. By inhibiting RANK Ligand, Denosumab prevents the development,
      activation and survival of osteoclasts. The FREEDOM study reported a 68 %
      reduction of vertebral fractures, 20 % of non-vertebral fractures and 40 % of hip
      fractures after 3 years in post-menopausal women with osteoporosis receiving
      denosumab 60 mg sc every six months vs. placebo. Five years extension of the
      denosumab group showed a further decrease in the rate of both vertebral and non
      vertebral fractures, whereas BMD at spine and hip increased continuously. There
      was no increase in the rate of adverse events year after year, including of
      infections, cancer, atypical fractures, delayed fracture healing or ONJ. Clinical
      hypocalcemia was rare in the context of calcium and vitamin D supplementation.
      Pre-planned and post-hoc subgroup analyses have further shown the anti-fracture
      efficacy of denosumab in high-risk subgroups, such as older women and those with
      low T-scores and/or prevalent vertebral fractures. Denosumab withdrawal is
      accompanied by a transient rebound of bone turnover markers and a proportional
      BMD loss. Smaller randomized controlled studies have shown that denosumab further
      improves BMD after one year compared to alendronate.

PMID- 22403112
TI  - [Bone anabolic treatment with Teriparatide].
AB  - The recombinant amino-terminal fragment of human parathyroid hormone
      (Teriparatide) is a bone anabolic agent which reduces fracture risk by increasing
      bone mass and improving bone microarchitecture. Teriparatide reduces vertebral
      fracture risk by 65 % and non-vertebral by 50 %. Its efficacy is higher as
      bisphosphonates to prevent corcicosteroid-induced osteoporosis. Teriparatide may
      also have a direct effect on bone pain. Teriparatide may be initiating
      immediately after an anticatabolic agent. However, it is not recommended to
      associate both treatments. At the end of teripatide treatment, an anticatabolic
      agent may be given. According to cost-effectiveness studies, Teriparatide should
      be considered as first line treatment for postmenopausal women and for men with
      severe osteoporosis.

PMID- 22403113
TI  - [Epidemiology and treatment of osteoporosis in men].
AB  - Osteoporosis is a disease characterized by an increased fragility of bone due to
      micro and macro structural changes of bone tissue and as a consequence a higher
      risk of fractures. Both women and men can be concerned by the problem, but in men
      a secondary origin is generally found with less fractures than in women, but with
      more morbidity. Both the diagnosis and the therapy are relatively similar in men
      as compared to women with postmenopausal osteoporosis. This paper is aimed at
      critically discussing the various differences in osteoporosis between men and
      women starting with some epidemiological considerations and ending with the
      therapeutical aspects.

PMID- 22403114
TI  - [Strategies of early rehabilitation in acute care of patients with vertebral
      fractures].
AB  - Due to the aging population the number of vertebral fractures will increase in
      the next years. In the acute care setting the pain treatment of patients with
      acute vertebral fractures is highly important. Part of the acute pain treatment
      is the early rehabilitative intervention of the treating team consisting of
      physicians, nurses and physiotherapists. In the acute care setting mostly
      rheumatologists, orthopaedic surgeons and physical therapy physicians are the
      treating physicians. Individual physiotherapy and patient communication and
      instruction are most important in this acute care setting. Special techniques of
      mobilisation and positioning are instructed. The guidelines of pain therapy in
      elderly geriatric patients have to be observed. In the last decade opioid therapy
      is one of the cornerstones of pharmacotherapy. For posture training and
      stabilization individual corselets have to be adapted. The aim is to stabilize
      the vertebral column and to avoid further anterior or posterior compression of
      the vertebral body. In the secondary prevention novel therapy programs are
      discussed.

PMID- 22403115
TI  - [Osteoporosis - whom to treat? The importance of FRAX(r) in Switzerland].
AB  - The WHO fracture risk assessment tool FRAX(r) is a computer based algorithm that
      provides models for the assessment of fracture probability in men and women. The
      approach uses easily obtained clinical risk factors (CRFs) to estimate 10-year
      probability of a major osteoporotic fracture (hip, clinical spine, humerus or
      wrist fracture) and the 10-year probability of a hip fracture. The estimate can
      be used alone or with femoral neck bone mineral density (BMD) to enhance fracture
      risk prediction. FRAX(r) is the only risk engine which takes into account the
      hazard of death as well as that of fracture. Probability of fracture is
      calculated in men and women from age, body mass index, and dichotomized variables
      that comprise a prior fragility fracture, parental history of hip fracture,
      current tobacco smoking, ever long-term use of oral glucocorticoids, rheumatoid
      arthritis, other causes of secondary osteoporosis, daily alcohol consumption of 3
      or more units daily. The relationship between risk factors and fracture
      probability was constructed using information of nine population-based cohorts
      from around the world. CRFs for fracture had been identified that provided
      independent information on fracture risk based on a series of meta-analyses. The
      FRAX(r) algorithm was validated in 11 independent cohorts with in excess of 1
      million patient-years, including the Swiss SEMOF cohort. Since fracture risk
      varies markedly in different regions of the world, FRAX(r) models need to be
      calibrated to those countries where the epidemiology of fracture and death is
      known. Models are currently available for 31 countries across the world. The
      Swiss-specific FRAX(r) model was developed very soon after the first release of
      FRAX(r) in 2008 and was published in 2009, using Swiss epidemiological data,
      integrating fracture risk and death hazard of our country. Two FRAX(r)-based
      approaches may be used to explore intervention thresholds. They have recently
      been investigated in the Swiss setting. In the first approach the guideline that
      individuals with a fracture probability equal to or exceeding that of women with
      a prior fragility fracture should be considered for treatment is translated into
      thresholds using 10-year fracture probabilities. In that case the threshold is
      age-dependent and increases from 16 % at the age of 60 ys to 40 % at the age of
      80 ys. The second approach is a cost-effectiveness approach. Using a FRAX(r)
      based intervention threshold of 15 % for both, women and men 50 years and older,
      should permit cost-effective access to therapy to patients at high fracture
      probability in our country and thereby contribute to further reduce the growing
      burden of osteoporotic fractures.

PMID- 22403116
TI  - Informatics in radiology: use of CouchDB for document-based storage of DICOM
      objects.
AB  - Picture archiving and communication systems traditionally have depended on schema
      based Structured Query Language (SQL) databases for imaging data management. To
      optimize database size and performance, many such systems store a reduced set of
      Digital Imaging and Communications in Medicine (DICOM) metadata, discarding
      informational content that might be needed in the future. As an alternative to
      traditional database systems, document-based key-value stores recently have
      gained popularity. These systems store documents containing key-value pairs that
      facilitate data searches without predefined schemas. Document-based key-value
      stores are especially suited to archive DICOM objects because DICOM metadata are
      highly heterogeneous collections of tag-value pairs conveying specific
      information about imaging modalities, acquisition protocols, and vendor-supported
      postprocessing options. The authors used an open-source document-based database
      management system (Apache CouchDB) to create and test two such databases; CouchDB
      was selected for its overall ease of use, capability for managing attachments,
      and reliance on HTTP and Representational State Transfer standards for accessing
      and retrieving data. A large database was created first in which the DICOM
      metadata from 5880 anonymized magnetic resonance imaging studies (1,949,753
      images) were loaded by using a Ruby script. To provide the usual DICOM query
      functionality, several predefined "views" (standard queries) were created by
      using JavaScript. For performance comparison, the same queries were executed in
      both the CouchDB database and a SQL-based DICOM archive. The capabilities of
      CouchDB for attachment management and database replication were separately
      assessed in tests of a similar, smaller database. Results showed that CouchDB
      allowed efficient storage and interrogation of all DICOM objects; with the use of
      information retrieval algorithms such as map-reduce, all the DICOM metadata
      stored in the large database were searchable with only a minimal increase in
      retrieval time over that with the traditional database management system. Results
      also indicated possible uses for document-based databases in data mining
      applications such as dose monitoring, quality assurance, and protocol
      optimization.

PMID- 22403117
TI  - Quality initiatives: guidelines for use of medical imaging during pregnancy and
      lactation.
AB  - The use of computed tomography (CT) and magnetic resonance (MR) imaging has
      increased tremendously in the past 2 decades. Hence, pregnant and breast-feeding
      women, although generally healthier than the population at large, are also more
      likely to require contrast material-enhanced imaging. When a contrast-enhanced CT
      or MR imaging study is being considered for a pregnant or lactating patient, the
      potential risks to the fetus related to exposure to radiation, high magnetic
      fields, or contrast agents must be considered and weighed carefully against the
      risks of potential misdiagnosis due to withholding contrast agents and imaging
      studies. Fetal radiation doses up to 1 mGy are considered acceptable; with larger
      doses, the risk of carcinogenesis approximately doubles, although it remains low
      in absolute terms. No damage to a developing human fetus caused by MR imaging
      exposure has been documented. However, caution is advised, and risks and benefits
      must always be considered before evaluating a pregnant patient with MR imaging.
      The use of iodinated contrast agents is generally safe during pregnancy;
      nevertheless, these agents should be used with caution due to the risk of fetal
      hypothyroidism and should be administered only when the clinical situation
      clearly requires doing so. The use of gadolinium-based contrast agents during
      pregnancy remains controversial due to lack of human clinical data and potential
      toxicity. Use of all contrast agents is considered safe during lactation. It is
      hoped that this knowledge will help radiologists develop a consensus with their
      clinical colleagues regarding case management of pregnant and lactating patients.

PMID- 22403118
TI  - The rise of dodgy insurance claims and the huge price of negligent medical
      treatment to the National Health Service.

PMID- 22403119
TI  - The long-term outcome for emotional and behavioural problems.
AB  - Long-term outcome of psychological problems in childhood is important in a
      variety of ways including understanding disease entities, managing treatment and
      implementing research. It is of particular importance to courts in cases
      involving children. Judges have the unenviable task of determining best action
      for the future of children. Research is now available showing linkages between
      childhood and adult disorder but also revealing increasing complexity of factors
      determining outcome. A model of child to adult continuity can be constructed
      showing linkages between genetic influence, intrauterine environment, perinatal
      risks, early upbringing and lifetime risk and resilience influences. Known
      continuities of behaviours are traced from child to adult life. The presentation
      is intended to give a glimpse of some of the data available to assist in decision
      making. Childhood determination of disorders such as schizophrenia may enable
      treatment to prevent further damage. Exciting developments particularly in
      genetics and functional imaging, will radically improve data over the next few
      years, possibly challenging currently held beliefs. At present expert witness
      contribution is under challenge but knowledge of the continuities can save court
      time, help prevent future heartache for vulnerable children, and later cost to
      the taxpayer.

PMID- 22403120
TI  - Spurious claims for health-care products: an experimental approach to evaluating
      current UK legislation and its implementation.
AB  - The lay media, and especially the Internet, contain many misleading claims for
      health products which have previously been inadequately regulated by consumer
      law. This was an experimental interventional survey within a consumer health-care
      setting. Three health products were chosen on the basis of being widely available
      on the UK market and having no available evidence of effectiveness. Twelve
      volunteers submitted 39 complaints to Consumer Direct (UK portal for the
      regulator Trading Standards) regarding false health claims, and 36 complaints
      were followed up for a maximum of 4.8 months. The mean time from submission of
      complaints to Consumer Direct to acknowledgement by the relevant Trading
      Standards office was 13 days. There were no responses from Trading Standards for
      22% of complaints. At the end of the study one supplier had amended their website
      following Trading Standards advice, but did not stop all health claims. Another
      stopped advertising their product on the Internet and the third continued the
      health claims unchanged. EU directive 2005/29/EC is largely ineffective in
      preventing misleading health claims for consumer products in the UK.

PMID- 22403121
TI  - Withdrawing life support.

PMID- 22403122
TI  - Enforcement costs: some humanitarian alternatives to stronger patent rights.
AB  - Diseases that cause comparatively few problems in developed countries kill
      millions of people in the Third World each year. In many cases, people die
      because they cannot afford the medication needed to save their lives. In others,
      there are simply no drugs available because there are no wealthy western patients
      to justify pharmaceutical companies investing in a cure. This reveals a deep
      seated problem within the patent system and the pharmaceutical industry that
      emphasises markets and profits at the expense of health and global welfare.
      Global efforts have seen substantial improvements in access to medicines in
      isolated areas, but with international agreements driving towards stronger patent
      protection and the expiry date for the TRIPS grace period fast approaching, it is
      time to consider alternatives which will allow the patent system to work for the
      humanitarian cause rather than against it. This paper considers two such problems
      in the patent system and pharmaceutical industry - prohibitive pricing and
      misdirected incentives - to offer a mode of regulation and enforcement that will
      support both a viable pharmaceutical industry and the human right to health and
      medication.

PMID- 22403123
TI  - Legal terrorism in domestic violence -- an Indian outlook.
AB  - Marriage in India is a voluntary union for life of one man and one woman to the
      exclusion of all others. It is a social association where the husband has the
      responsibility to take care of and maintain his wife and not to neglect his
      duties. But in relation to this great institution, the problem of the "dowry"
      still persists. Women are ill-treated, harassed, killed or divorced for the
      simple reason that they do not get a dowry or do not get a sufficiently large
      one. To safeguard the interest of women against the cruelty they face within the
      four walls of their matrimonial home, the Indian Penal Code 1860 was amended in
      1983 and section 498A was added. This deals with "Matrimonial Cruelty" to a
      woman. Matrimonial Cruelty in India is a cognizable, non-bailable and non
      compoundable offence. Notwithstanding that the practice of demanding dowries was
      made illegal in India over 50 years ago, the (London) Times on 18 January 2012
      reported that a study in 2007 concluded that "there is a dowry-related death in
      India every four hours". Official statistics in India show there were 8,391 dowry
      related deaths in 2010, and there may well have been more. Why has leglislation
      that criminalises these appalling practices failed to stop them?

PMID- 22403124
TI  - Dissonant legal and biological versions of the maternal-fetal relationship.

PMID- 22403125
TI  - Health related quality of life in patients with critical limb ischemia.
AB  - Critical limb ischemia (CLI) is the terminal stage of peripheral artery disease.
      Research in recent years has been largely focussed on treatment options such as
      bypass surgery / endovascular treatment, surgery / primary amputation and
      additional benefits of supportive pharmacotherapy. Despite this plethora of
      treatment options, however, patients continue to have a reduced health related
      quality of life (HRQoL). Aim of the present work was to review the available
      evidence of improvement of HRQoL with regard to different treatment options. We
      found that a number of clinical studies have been conducted using HRQoL measures
      mostly as secondary outcomes in patients with CLI and other less severe forms of
      peripheral arterial disease. The studies demonstrate a consistent improvement of
      HRQoL over baseline within the first few months after the intervention.
      Prostaglandins, but no other pharmacotherapies, appear to be effective in
      patients without an option for revascularization. Due to a largely differing
      patient population under investigation and the different degrees of disease
      progression it appears difficult however to compare different treatment options
      with respect to their impact on HRQoL. HRQoL improvement as a predefined endpoint
      of novel therapeutic approach studies should be considered more consequently.

PMID- 22403126
TI  - Drug-eluting stents for treatment of focal infrapopliteal lesions.
AB  - We have investigated the role of drug-eluting stents on patency rates after
      treatment of focal infrapopliteal lesions in patients with intermittent
      claudication and critical limb ischemia. Reports indicate that drug-eluting
      stents reduce the risk of restenosis after percutaneous infrapopliteal artery
      revascularization. A Pub Med, EMBASE, Cochrane database review search of non
      randomized studies investigating patency rates, target lesion revascularisation
      rates, limb salvage rates and mortality rates in an up to 3-year follow-up period
      after drug-eluting stent placement was conducted. In addition, preliminary
      results of randomized studies comparing drug-eluting stents with bare-metal
      stents and plain balloon angioplasty in treatment of focal infrapopliteal lesions
      were included in this review. A total of 1039 patients from 10 non-randomized and
      randomized studies were included. Most commonly used drug-eluting stents were
      sirolimus-eluting. The mean follow-up period was 12.6 (range 8 - 24). The mean 1
      year primary patency rate was 86 +/- 5 %. The mean target lesion
      revascularization rate and limb salvage rate was 9.9 +/- 5 % and 96.6 %+/-4 %,
      respectively. Results from non-randomized and preliminary results from
      prospective, randomized trials show a significant advantage for drug-eluting
      stents in comparison to plain balloon angioplasty and bare-metal stents
      concerning target lesion patency and in parts target lesion revascularisation. No
      trial reveals an advantage for drug-eluting stents with regard to limb salvage
      and mortality.

PMID- 22403127
TI  - Arterial stiffness, inflammatory and pro-atherogenic markers in gestational
      diabetes mellitus.
AB  - BACKGROUND: This study aims to determine whether gestational diabetes mellitus
      (GDM) is associated with increased arterial stiffness, inflammatory and pro
      atherogenic markers compared to age matched controls. PATIENTS AND METHODS: This
      is a cross-sectional study involving 53 pregnant women in the early third
      trimester of pregnancy consisting of 31 women with normal pregnancy and 22 women
      with GDM. Subjects were grouped into GDM and control groups based on modified
      oral glucose tolerance test results; they were considered GDM if fasting blood
      glucose (FBG) was >= 6.1 mmol/L and/or the two hours post-glucose intake was >=
      7.8 mmol/L. Arterial stiffness was assessed non-invasively using the parameters
      augmentation index (AIx) obtained via pulse wave analysis and carotid femoral
      pulse wave velocity (PWV). Tumor necrosis factor alpha (TNF-alpha), high
      sensitivity C- reactive protein (hsCRP) and plasminogen activator inhibitor-1
      (PAI-1) were measured using enzyme linked immunoassay technique (ELISA). Aortic
      and brachial blood pressure (BP) indices were also recorded. RESULTS: Mean ages
      and gestational ages (GA) for the control and GDM groups showed no significant
      differences (31.1 +/- 5.68 vs. 32.9 +/- 8.46 years; 29.0 +/- 2.43 vs. 29.6 +/-
      1.54 weeks respectively). FBG and 2 hour post-glucose levels were significantly
      higher in GDM; (5.27 +/- 1.19 vs. 3.94 +/- 0.44 mmol/L, p < 0.001; 9.66 +/- 1.76
      vs. 5.68 +/- 1.10 mmol/L, p < 0.001). TNF-alpha, PAI-1 and hsCRP levels were
      significantly higher in GDM compared to controls (0.81 +/- 0.15 vs. 0.72 +/- 0.13
      pg/ml, 54.48 +/- 13.07 vs. 36.16 +/- 15.58 cm/ml, 7.91 +/- 1.16 vs. 6.70 +/- 1.45
      mg/l respectively). PWV (8.28 +/- 1.48 vs. 7.97 +/- 1.12) and AIx (16.73 +/-
      10.98 vs. 16.13 +/- 9.64 %) were not significantly different between the two
      groups. No significant differences were seen for aortic and brachial BP, mean
      arterial pressure and body mass index. CONCLUSIONS: The inflammatory markers TNF
      alpha and hsCRP, and the pro-atherogenic marker PAI-1 were elevated in GDM
      compared to age matched controls. No significant difference was seen between the
      two groups in their arterial stiffness.

PMID- 22403128
TI  - Claudication, in contrast to angina pectoris, independently predicts mortality
      risk in the general population.
AB  - BACKGROUND: The aim of our analyses was to investigate whether claudication and
      angina pectoris, each defined and based on the answer to a single question, are
      predictive of future mortality. PROBANDS AND METHODS: The study population
      consisted of 3995 subjects selected from the population-based Study of Health In
      Pomerania (SHIP). Kaplan-Meier analysis and multivariable Cox proportional
      hazards regression analysis were used to analyze the association of angina
      pectoris and claudication with all-cause and cardiovascular mortality adjusted
      for major cardiovascular risk factors. RESULTS: At baseline, 417 individuals had
      symptoms of angina pectoris, and 323 had symptoms of claudication. During a
      median follow-up of 8.5 years, 277 individuals died. Individuals with
      claudication had a higher fully-adjusted all-cause mortality rate (Hazard Ratio
      (HR) 1.79; 95 % CI 1.34, 2.39, p < 0.001) and a higher sex- and age-adjusted
      cardiovascular mortality rate (HR 1.76; 95 % CI 1.03, 2.99, p = 0.038) compared
      to subjects without claudication. In contrast, subjects with angina pectoris had
      neither an elevated fully-adjusted all-cause mortality rate (HR 1.15; 95 % CI
      0.82, 1.61, p = 0.413) nor sex- and age-adjusted cardiovascular mortality rate
      (HR 0.71; 95 % CI 0.34, 1.48, p = 0.363) compared to those without this symptom.
      CONCLUSIONS: Claudication, in contrast to angina pectoris, is a strong,
      independent predictor of all-cause mortality.

PMID- 22403129
TI  - Doppler-ultrasound measurements in renal allografts depend on the patient's body
      position.
AB  - BACKGROUND: Due to anatomical reasons a position-dependent renal allograft artery
      stenosis is being discussed (e.g. only in patient's upright position). The
      tortuous course of the allograft artery complicates the direct, angle-dependent
      measurement of maximum systolic flow velocities (vmax). So indirect signs such as
      intraparenchymal vmax and resistance index might be helpful, but it is unknown
      how these values change physiologically when patient's body position changes.
      PATIENTS AND METHODS: We examined renal allografts of 60 patients (38 male, 22
      female) with stable graft function using B-Mode-, colour-coded duplex-sonography
      and pulsed-wave-Doppler. We measured vmax and RI-values of three interlobar
      arteries in the cortex and allograft artery in the hilus in patients standing
      upright and in horizontal position. Corresponding values were analyzed for
      significant differences. RESULTS: Intraparenchymal RI-values and vmax were
      significantly reduced in patients upright compared to the horizontal position (16
      %, MW=0.59 vs. MW=0.70, p < 0.001 resp. 6 %, MW=30.18 cm/s vs. MW=32.17 cm/s, p =
      0.045). Similar results could be detected in the renal hilus. CONCLUSIONS:
      Patients with stable graft-function show significant, position-dependent
      differences of the intraparenchymal and hilar RI-values and maximal systolic flow
      velocities. These changes of Doppler parameters has to be kept in mind for the
      correct diagnosis of a position dependent allograft artery stenosis.

PMID- 22403130
TI  - Catheter-directed foam sclerotherapy treatment of saphenous vein incompetence.
AB  - BACKGROUND: The aim of this study is to report the short-term results of catheter
      directed foam sclerotherapy (CDFS) in the treatment of axial saphenous vein
      incompetence. PATIENTS AND METHODS: Data of all patients undergoing CDFS for
      symptomatic primary incompetence of the great or small saphenous vein were
      prospectively collected. Treatment results in terms of occlusion rate and
      patients' grade of satisfaction were analysed. All successfully treated patients
      underwent clinical and duplex follow-up examinations one year postoperatively.
      RESULTS: Between September 2006 and September 2010, 357 limbs (337 patients) were
      treated with CDFS at our institution. Based on the CEAP classification, 64 were
      allocated to clinical class C3 , 128 to class C4, 102 to class C5 and 63 to class
      C6. Of the 188 patients who completed the one year follow up examination, 67 %
      had a complete and 14 % a near complete obliteration of the treated vessel. An
      ulcer-healing rate of 54 % was detected. 92 % of the patients were satisfied with
      the results of treatment. We registered six cases of thrombophlebitis and two
      cases of venous thromboembolism, all requiring treatment. CONCLUSIONS: The short
      term results of CDFS in patients with axial vein incompetence are acceptable in
      terms of occlusion and complications rates.

PMID- 22403131
TI  - Compression therapy in elderly and overweight patients.
AB  - BACKGROUND: According to the current demography of the western population, age
      and weight will have increasing impact on medical therapies. The aim of the
      analysis was to examine if there are differences in the use of compression
      therapy depending on age and BMI. PATIENTS AND METHODS: Questioning of 200
      consecutive phlebological patients (C2-C6) with a compression therapy time of > 2
      weeks. Analysis of 110 returned questionnaires. Sub-analysis according to age (>=
      60 years vs. < 60 years) and BMI (<25 kg/m2 vs. >=25 kg/m2) were made. RESULTS:
      Patients >= 60 years have a leg ulcer significantly more often than patients
      under 60 (20 % vs. 5.9 %, p = 0.03) and frequently need more help with the
      compression therapy (70.9 % vs. 47.1 %, p = 0.05). 14.6 % of those > 60 years
      even need the help of another person to apply compression. Patients >= 25 kg/m2
      have an ulcer stocking significantly more often (15 % vs. 4.3 %, p = 0.05) and
      need the help of family members to put on the compression therapy (11.7 % vs. 2.1
      %, p = 0.04). There is a tendency of patients >= 25 kg/m2 to complain more often
      about a constriction of compression therapy (35 % vs. 19.2 %, p = 0.06).
      CONCLUSIONS: There are special aspects that have to be regarded for compression
      therapy in elderly and overweight patients. Data should encourage prescribers,
      sellers and manufacturers of compression therapy to use compression in a very
      differentiated way for these patients and to consider: Is the recommended
      compression therapy right for this patient (pressure, material, type)? What
      advice and adjuvants do the patients need to get along more easily with the
      compression therapy? Are there any new materials or adjuvants that allow those
      increasing groups of people to get along with compression therapy alone?

PMID- 22403132
TI  - Mid-aortic syndrome: computed tomography angiography depicting extensive
      collateral circulation in an 11-year-old patient with thoracoabdominal aortic
      coarctation.
AB  - The mid-aortic syndrome is an uncommon clinical condition characterized by severe
      narrowing of the descending aorta, usually with involvement of its renal and
      visceral branches, presenting with uncontrollably elevated blood pressures of the
      upper body, renal and cardiac failure, intestinal ischemia, encephalopathy
      symptoms and claudication of the lower limbs, although clinical presentation is
      variable. In this article we report the case of an eleven-year-old patient with
      the initial diagnosis of a mid-aortic syndrome and present the computed
      tomography angiography pictures and reconstructions before and after surgical
      therapy.

PMID- 22403133
TI  - Late peripheral stent thrombosis due to stent fracture, vigorous exercise and
      hyporesponsiveness to clopidogrel.
AB  - Late peripheral arterial stent thrombosis usually occurs due to haemodynamically
      relevant in-stent restenosis. However, late stent thrombosis may be multicausal.
      We report here the well-documented case of a 69-year-old man with acute
      thrombosis of the stented superficial femoral artery after a long-distance
      bicycle tour. Catheter-directed thrombolysis revealed a residual stenosis located
      at a stent fracture site. In addition, platelet function tests revealed an
      inadequate platelet response to clopidogrel. In conclusion, stent fracture,
      strenuous exercise and hyporesponsiveness to clopidogrel may have contributed to
      the development of late peripheral stent thrombosis.

PMID- 22403134
TI  - Castleman's disease and arterial thrombosis: result of excessively elevated
      interleukin-6 plasma level?
AB  - Morbus Castleman is a benign non-clonal lymphoproliverative disorder.
      Immunomodulatory and antiproliferative drugs are used to treat this plasma cell
      disorder. We report the case of a 46-year old female patient with multicentric
      Castleman's disease and limb ischemia. Thrombotic occlusions of the popliteal and
      tibioperoneal arteries were treated by percutaneous thrombus aspiration. We
      discuss the role of increased interleukin-6 plasma levels during therapy with
      Tocilizumab, an antibody to interleukin-6 receptor, as a potential cause for
      arterial thrombosis.

PMID- 22403135
TI  - Sclerotherapy of lymphatic cysts of the leg with OK-432.
AB  - Lymphatic cysts can either represent lymphatic malformations (LMs) or may occur
      after trauma or operation. Independent of their etiology lymphatic cysts can
      cause functional impairment and recurrent skin infections. We report the
      successful use of OK-432 injected transcutanously to treat lymphatic macrocysts.
      Treatment of LMs with OK-432 has been reported to be a safe and minimally
      invasive procedure. The underlying mechanism is still unclear but injection leads
      to an inflammation of the wall resulting in occlusion or shrinkage of the cyst.

PMID- 22403137
TI  - Shiga toxin-producing Escherichia coli O157 : H7 shows an increased pathogenicity
      in mice after the passage through the gastrointestinal tract of the same host.
AB  - Haemolytic uraemic syndrome (HUS) is a rare but life-threatening complication of
      Shiga toxin (Stx)-producing Escherichia coli (STEC) infections, characterized by
      acute renal failure, thrombocytopenia and haemolytic anaemia. Although the main
      infection route is the consumption of contaminated food or water, person-to
      person transmission has been suggested in several situations. Moreover,
      epidemiological data indicate that the horizontal transmission of several
      pathogens, including STEC, among individuals of the same species requires
      significantly lower doses than those used in animal models infected with
      laboratory-cultured bacteria. Thus, the aim of this study was to evaluate whether
      the passage of a clinically isolated STEC strain through the gastrointestinal
      tract of mice affects its pathogenicity in mice. To test this, weaned mice were
      orally inoculated by gavage with either an E. coli O157:H7 isolate from an HUS
      patient, or the same strain recovered from stools after one or two successive
      passages through the gastrointestinal tract of the mice. We show that stool
      recovered strains are able to induce a more generalized and persistent
      colonization than the parent strain. Furthermore, a 10(4)-fold-reduced inoculum
      of the stool-recovered strains still causes gut colonization and mouse mortality,
      which are not observed with the parent strain. These results indicate an
      increased pathogenicity in stool-recovered strains that may be associated with an
      increased ability to colonize the mouse intestine.

PMID- 22403138
TI  - A comparison of molecular methods for hepatitis B virus (HBV) DNA detection from
      oral fluid samples.
AB  - The objective of the present study was to evaluate four commercial DNA extraction
      methods and three PCR protocols for hepatitis B virus (HBV) detection in
      artificially contaminated oral fluid samples. The extraction protocols were
      selected based on ease of use and cost, and were also compared with respect to
      sensitivity and cost. Prior PCR optimization was conducted, in which the sample
      volume for DNA extraction and the concentrations of DNA and Taq DNA polymerase in
      the PCR were adjusted. One-round PCR, used to amplify the core region of the HBV
      genome, achieved high levels of sensitivity in comparison with nested and semi
      nested PCR experiments that were designed for the amplification of HBV surface
      protein genes. Of the four extraction protocols evaluated, the RTP DNA/RNA Virus
      Mini kit and the QIAamp DNA Mini kit gave the highest recovery rates, presenting
      20 copies of HBV DNA ml(-1) as the limit of detection. These results suggest that
      HBV DNA can be detected from oral fluid samples but that the optimization of the
      PCR assays and the choice of extraction methods must be determined by
      laboratories before the implementation of this method in routine diagnostics.

PMID- 22403139
TI  - Colicin insensitivity correlates with a higher prevalence of extraintestinal
      virulence factors among Escherichia coli isolates from skin and soft-tissue
      infections.
AB  - Colicins are toxic proteins with a narrow killing spectrum that are produced by
      colicinogenic Escherichia coli strains. The aim of this study was to analyse
      systematically whether extra-intestinal virulence potential is linked to colicin
      (in)sensitivity. In total, 102 well-characterized E. coli isolates from skin and
      soft-tissue infections (SSTIs) were exposed to 17 single-colicin-producing
      strains, and the correlation between insensitivity to colicin and phylogenetic
      group as well as the extra-intestinal virulence potential of the SSTI strains was
      examined. The results showed that SSTI strains belonging to the B2 phylogenetic
      group were statistically significantly associated with insensitivity to at least
      ten colicins, and several colicin insensitivities were correlated with virulence
      factors. As far as is known, this is the first study to report such correlations.

PMID- 22403140
TI  - Wild birds as biological indicators of environmental pollution: antimicrobial
      resistance patterns of Escherichia coli and enterococci isolated from common
      buzzards (Buteo buteo).
AB  - A total of 36 Escherichia coli and 31 enterococci isolates were recovered from 42
      common buzzard faecal samples. The E. coli isolates showed high levels of
      resistance to streptomycin and tetracycline. The following resistance genes were
      detected: bla(TEM) (20 of 22 ampicillin-resistant isolates), tet(A) and/or tet(B)
      (16 of 27 tetracycline-resistant isolates), aadA1 (eight of 27 streptomycin
      resistant isolates), cmlA (three of 15 chloramphenicol-resistant isolates),
      aac(3)-II with/without aac(3)-IV (all seven gentamicin-resistant isolates) and
      sul1 and/or sul2 and/or sul3 [all eight sulfamethoxazole/trimethoprim-resistant
      (SXT) isolates]. intI1 and intI2 genes were detected in four SXT-resistant
      isolates. The virulence-associated genes fimA (type 1 fimbriae), papC (P
      fimbriae) and aer (aerobactin) were detected in 61.1, 13.8 and 11.1% of the
      isolates, respectively. The isolates belonged to phylogroups A (47.2%), B1
      (8.3%), B2 (13.9%) and D (30.5%). For the enterococci isolates, Enterococcus
      faecium was the most prevalent species (48.4%). High levels of tetracycline and
      erythromycin resistance were found among our isolates (87 and 81%, respectively).
      Most of the tetracycline-resistant strains carried the tet(M) and/or tet(L)
      genes. The erm(B) gene was detected in 80% of erythromycin-resistant isolates.
      The vat(D) and/or vat(E) genes were found in nine of the 17 quinupristin
      dalfopristin-resistant isolates. The enterococcal isolates showing high-level
      resistance for kanamycin, gentamicin and streptomycin contained the aph(3')-IIIa,
      aac(6')-aph(2") and ant(6)-Ia genes, respectively. This report reveals that
      common buzzards seem to represent an important reservoir, or at least a source,
      of multi-resistant E. coli and enterococci isolates, and consequently may
      represent a considerable hazard to human and animal health by transmission of
      these isolates to waterways and other environmental sources via their faecal
      deposits.

PMID- 22403141
TI  - Diagnosis of infective endocarditis: comparison of the LightCycler SeptiFast real
      time PCR with blood culture.

PMID- 22403142
TI  - Prosthetic valve endocarditis caused by Bordetella holmesii, an Acinetobacter
      lookalike.
AB  - We report a case of fulminant endocarditis on a prosthetic homograft aortic valve
      caused by Bordetella holmesii, which was successfully managed by surgical valve
      replacement and antibiotic treatment. B. holmesii, a strictly aerobic, small,
      Gram-negative coccobacillus, has been implicated as an infrequent cause of a
      pertussis-like syndrome and other respiratory illnesses. However, B. holmesii is
      also a rare cause of septicaemia and infective endocarditis, mostly in
      immunocompromised patients. To our knowledge, this is the first report of B.
      holmesii endocarditis on a prosthetic aortic valve. Routine laboratory testing
      initially misidentified the strain as Acinetobacter sp. Correct identification
      was achieved by 16S rRNA gene and outer-membrane protein A (ompA) gene
      sequencing. Interestingly, matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry also produced an accurate species-level identification.
      Subsequent susceptibility testing and review of the literature revealed
      ceftazidime, cefepime, carbapenems, aminoglycosides, fluoroquinolones,
      piperacillin/tazobactam, tigecycline and colistin as possible candidates to treat
      infections caused by B. holmesii.

PMID- 22403143
TI  - Increasing the sensitivity of the BinaxNOW Legionella urinary antigen
      immunochromatographic test by additional readings at later time points.

PMID- 22403144
TI  - [Natural course of septo-optic dysplasia: retrospective analysis of 20 cases].
AB  - INTRODUCTION: Septo-optic dysplasia (SOD) is the variable combination of signs of
      dysgenesis of the midline of the brain, hypoplasia of the optic nerves and
      hypothalamus-pituitary dysfunction, which is sometimes associated with a varied
      spectrum of malformations of the cerebral cortex. AIMS: To describe the natural
      history and neuroimaging findings in a series of 20 diagnosed patients. PATIENTS
      AND METHODS: We review the epidemiological, clinical and neuroimaging
      characteristics of 20 consecutive patients diagnosed with SOD between January
      1985 and January 2010. Data obtained from computerised tomography, magnetic
      resonance imaging of the head, electroencephalogram, visual evoked potentials,
      ophthalmological evaluation, karyotyping and endocrinological studies were
      analysed. In seven patients, a study of the gene Homeobox HESX1 was conducted.
      RESULTS: Pathological antecedents in the first three months of gestation were
      presented by 60% of the cases, with normal results in the foetal ultrasound
      scans. Clinically, the most striking features were visual manifestations (85%),
      endocrine disorders (50%), mental retardation (60%) and epileptic seizures (55%).
      Fifty-five per cent were associated to abnormal neuronal migration. In 45%, SOD
      was the only finding in the neuroimaging scans. Karyotyping was performed in all
      cases, the results being normal. Gene HESX1 was positive in two of the seven
      cases studied (both with isolated SOD). None of those with mutation in gene HESX1
      presented familial consanguinity. No gene study was conducted with the parents.
      CONCLUSIONS: SOD must be classified as a heterogeneous malformation syndrome,
      which is associated to multiple brain, ocular, endocrine and systemic anomalies.
      The most severe forms are associated with abnormal neuronal migration and
      cortical organisation.

PMID- 22403145
TI  - [Description of a series of cases of hypnic headache. Differentiation between
      sexes].
AB  - INTRODUCTION: Hypnic headache is an infrequent type of primary headache
      characterised by appearing almost exclusively during sleep and by waking the
      patient up. The pain is dull (generally bilateral), is not associated to
      autonomic signs and usually appears from the age of 50 onwards. PATIENTS AND
      METHODS: A 10-year prospective study was conducted which describes the patients
      with hypnic headache who were attended in a specialised headache clinic. Data
      collected include demographic variables, the characteristics of the pain and
      response to treatment. Data from males and from females were compared. RESULTS:
      Twenty-four patients were diagnosed with hypnic headache: 15 females and 9 males.
      There were no differences between sexes as regards the age at onset of the pain,
      the time elapsed until diagnosis, the number of episodes per month or the amount
      of time the pain lasted. The males reported a more intense pain (measured by
      means of the analogical visual scale) than the females. Neither were there any
      differences in terms of the presence of arterial hypertension or obstructive
      sleep apnoea syndrome. Response to different symptomatic and preventive
      treatments was scarce and with no differences between sexes. CONCLUSIONS: The
      pain in hypnic headaches is more intense in males, although this needs to be
      corroborated in longer series. Further advances need to be made in the
      pathophysiology of this kind of headache so as to be able to find more efficient
      preventive pharmacological agents.

PMID- 22403146
TI  - [REHACOP: a cognitive rehabilitation programme in psychosis].
AB  - INTRODUCTION: In this work we present REHACOP, a programme of cognitive
      rehabilitation in psychosis. MATERIALS AND METHODS: The foundation of the REHACOP
      programme (its structure, materials, aims, work methodology and means of
      implementation) are described in detail. RESULTS AND CONCLUSIONS: This new
      therapeutic tool is presented with the aim of being of use to guide professionals
      who seek to design an intervention of this kind in samples of patients with
      schizophrenia or other pathologies.

PMID- 22403147
TI  - [Multiple abnormal innervation of the hand in one patient. Electrophysiological
      diagnosis].
AB  - INTRODUCTION: Nerve anastomoses in the hand are deviations from the anatomical
      norm. They do not lead to illness, but still they are events related with
      electrodiagnostic difficulties and, due to their unexpected presentation, also
      with iatrogenesis in regional surgical interventions. CASE REPORT: We report the
      neurophysiological study conducted on a 45-year-old female who was found to have
      Riche-Cannieu-type motor anastomosis between the median and ulnar branches in the
      palm of the hand, complete innervation of the 4th finger by the ulnar nerve and
      complete innervation by the superficial radial of the back of the hand.
      CONCLUSIONS: Anatomical descriptions of abnormal innervations in the hand are
      frequent, especially of the sensory kind. They do not usually give rise to any
      problems, even when the communicating branch is injured, probably owing to the
      scant participation of axons that usually occurs in anastomosis. They are not
      difficult to recognise by means of electroneurography if we are aware of their
      different types and we have a good knowledge of the anatomical routes. This will
      enable us to develop accurate diagnostic protocols. Knowledge of these variants
      will prevent electrodiagnostic errors and surgical iatrogenic effects from
      occurring.

PMID- 22403148
TI  - [Resveratrol: a neuroprotective polyphenol in the Mediterranean diet].
AB  - INTRODUCTION: Resveratrol is a polyphenol present in grapes, some nuts and dried
      fruits, and red wine. A number of beneficial properties have been attributed to
      this compound. Its potential neuroprotective effects are the subject of much
      research today. AIM: To review the effects of resveratrol, and more particularly
      those related to its capacity to offer protection against the neurodegeneration
      associated with several pathologies and traumatic injuries in the central nervous
      system. DEVELOPMENT: It has been suggested that the daily consumption of red
      wine, and therefore of resveratrol, could account for the so-called 'French
      paradox', according to which the population in the south of France, despite
      eating a diet that is relatively high in saturated fats, presents a low risk of
      heart disease. From this first evidence of the cardioprotective properties of
      resveratrol, its study has been extended and equally attractive
      biopharmacological effects have now been found in many different fields. Thus,
      neuroprotective effects have been found in models of neurodegeneration
      (Alzheimer's, Parkinson's or Huntington's disease, or diverse neuropathies), of
      ischaemia and of brain and spinal cord injury, but further clinical data are
      still needed in this regard. CONCLUSIONS: Although few studies have been
      conducted in humans, recent findings in experimental models of neurological
      pathology are encouraging and open up the doors to future clinical studies that
      will allow the therapeutic value of resveratrol to be determined.

PMID- 22403149
TI  - [Acquired brain injury: a proposal for its definition, diagnostic criteria and
      classification].
AB  - Acquired brain injury is a heterogeneous clinical concept that goes beyond the
      limits of the classical medical view, which tends to define processes and
      diseases on the grounds of a single causation. Although in the medical literature
      it appears fundamentally associated to traumatic brain injury, there are many
      other causes and management is similar in all of them, during the post-acute and
      chronic phases, as regards the measures to be taken concerning rehabilitation and
      attention to dependence. Yet, despite being an important health issue, today we
      do not have a set of diagnostic criteria or a classification for this condition.
      This is a serious handicap when it comes to carrying out epidemiological studies,
      designing specific care programmes and comparing results among different
      programmes and centres. Accordingly, the Extremadura Acquired Brain Injury Health
      Care Plan working group has drawn up these proposed diagnostic criteria,
      definition and classification. The proposal is intended to be essentially
      practical, its main purpose being to allow correct identification of the cases
      that must be attended to and to optimise the use of neurorehabilitation and
      attention to dependence resources, thereby ensuring attention is provided on a
      fair basis.

PMID- 22403150
TI  - [Diagnostic validity of attention deficit/hyperactivity disorder: from
      phenomenology to neurobiology (II)].
AB  - The diagnostic criteria for the attention deficit/hyperactivity disorder (ADHD)
      were defined by the American Psychiatric Association in the Diagnostic and
      Statistical Manual of Mental Disorders, fourth version. ADHD is a neuro
      psychiatric disorder associated with impairments in everyday life and behavioral
      dysregulation (i.e. inattention, hyper-activity and impulsivity), and it has
      showed empirical evidence from clinical, pharmacological, and psychometric
      studies. Nevertheless, the role of neurobiological impairments in the
      presentation of the symptoms remains unclear. For this paper, the authors
      reviewed Spanish and English literature that support the neurobiological validity
      of the disorder, aimed to present evidence associated with its cognitive and
      behavioral phenotype (e.g. in: neuropsychology, electrophysiology, structural and
      functional magnetic resonance imaging, neurochemistry and genetics).
      Additionally, an integrative theoretical clinical and scientific proposal is
      presented. Finally, the introduction of neurobiological marker as part of the
      definitive diagnosis is suggested, as a started point for the identification of
      therapeutic targets.

PMID- 22403151
TI  - [Post-traumatic resolution of an intracranial arachnoid cyst].

PMID- 22403153
TI  - [Descriptive analysis of hospital admissions due to functional causes].

PMID- 22403152
TI  - [Spontaneous epidural haematoma, an infrequent cause of cervicodorsal pain].

PMID- 22403154
TI  - Neuroimaging self-esteem: a fMRI study of individual differences in women.
AB  - Although neuroimaging studies strongly implicate the medial prefrontal cortex
      (ventral and dorsal), cingulate gyrus (anterior and posterior), precuneus and
      temporoparietal cortex in mediating self-referential processing (SRP), little is
      known about the neural bases mediating individual differences in valenced SRP,
      that is, processes intrinsic to self-esteem. This study investigated the neural
      correlates of experimentally engendered valenced SRP via the Visual-Verbal Self
      Other Referential Processing Task in 20 women with fMRI. Participants viewed
      pictures of themselves or unknown other women during separate trials while
      covertly rehearsing 'I am' or 'She is', followed by reading valenced trait
      adjectives, thus variably associating the self/other with positivity/negativity.
      Response within dorsal and ventral medial prefrontal cortex, cingulate cortex and
      left temporoparietal cortex varied with individual differences in both pre-task
      rated self-descriptiveness of the words, as well as task-induced affective
      responses. Results are discussed as they relate to a social cognitive and
      affective neuroscience view of self-esteem.

PMID- 22403155
TI  - Counterfactual thinking: an fMRI study on changing the past for a better future.
AB  - Recent studies suggest that a brain network mainly associated with episodic
      memory has a more general function in imagining oneself in another time, place or
      perspective (e.g. episodic future thought, theory of mind, default mode). If this
      is true, counterfactual thinking (e.g. 'If I had left the office earlier, I
      wouldn't have missed my train.') should also activate this network. Present
      functional magnetic resonance imaging (fMRI) study explores the common and
      distinct neural activity of counterfactual and episodic thinking by directly
      comparing the imagining of upward counterfactuals (creating better outcomes for
      negative past events) with the re-experiencing of negative past events and the
      imagining of positive future events. Results confirm that episodic and
      counterfactual thinking share a common brain network, involving a core memory
      network (hippocampal area, temporal lobes, midline, and lateral parietal lobes)
      and prefrontal areas that might be related to mentalizing (medial prefrontal
      cortex) and performance monitoring (right prefrontal cortex). In contrast to
      episodic past and future thinking, counterfactual thinking recruits some of these
      areas more strongly and extensively, and additionally activates the bilateral
      inferior parietal lobe and posterior medial frontal cortex. We discuss these
      findings in view of recent fMRI evidence on the working of episodic memory and
      theory of mind.

PMID- 22403156
TI  - Sensitivity to dioxin decreases as zebrafish mature.
AB  - The embryos of teleost fish are exquisitely sensitive to the toxic effects of
      exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, several lines of
      evidence suggest that adults are less sensitive to TCDD. To better understand and
      characterize this difference between early life stage and adults, we exposed
      zebrafish (Danio rerio) to graded TCDD concentrations at different ages. The
      LD(50) for embryos exposed at 1 day post-fertilization (dpf) was more than an
      order of magnitude lower than it was for juveniles exposed at 30 dpf. The latency
      between exposure and response also increased with age. Embryo toxicity was
      characterized by marked cardiovascular collapse and heart malformation, whereas
      juveniles exposed at 30 dpf had no detectable cardiovascular toxicity. In
      juveniles, the effects of TCDD exposure included stunted growth, altered
      pigmentation, and skeletal malformations. Furthermore, the transcriptional
      profile produced in hearts exposed to TCDD as embryos had very little overlap
      with the transcriptional changes induced by TCDD at 30 dpf. The early cardiotoxic
      response was associated with fish exposed prior to metamorphosis from the larval
      to the adult body plan at approximately 14 dpf. Our results show conclusively
      that the developmental stage at the time of exposure controls the toxic response
      to TCDD.

PMID- 22403158
TI  - Ochratoxin a and mitotic disruption: mode of action analysis of renal tumor
      formation by ochratoxin A.
AB  - The mycotoxin and food contaminant ochratoxin A (OTA) is a potent renal
      carcinogen in rodents, but its mode of action (MoA) is still poorly defined. In
      2006, the European Food Safety Authority concluded that there is a "lack of
      evidence for the existence of OTA-DNA adducts" and thus insufficient evidence to
      establish DNA reactivity as a MoA for tumor formation by OTA. In reviewing the
      available database on OTA toxicity, a MoA for renal carcinogenicity of OTA is
      developed that involves a combination of genetic instability and increased
      proliferative drive as consequences of OTA-mediated disruption of mitosis,
      whereby the organ- and site-specificity of tumor formation by OTA is determined
      by selective renal uptake of OTA into the proximal tubule epithelium. The
      proposed MoA is critically assessed with respect to concordance of dose-response
      of the suggested key events and tumor formation, their temporal association,
      consistency, and biological plausibility. Uncertainties, data gaps and needs for
      further research are highlighted.

PMID- 22403157
TI  - Irritancy and allergic responses induced by exposure to the indoor air chemical 4
      oxopentanal.
AB  - Over the last two decades, there has been an increasing awareness regarding the
      potential impact of indoor air pollution on human health. People working in an
      indoor environment often experience symptoms such as eye, nose, and throat
      irritation. Investigations into these complaints have ascribed the effects, in
      part, to compounds emitted from building materials, cleaning/consumer products,
      and indoor chemistry. One suspect indoor air contaminant that has been identified
      is the dicarbonyl 4-oxopentanal (4-OPA). 4-OPA is generated through the
      ozonolysis of squalene and several high-volume production compounds that are
      commonly found indoors. Following preliminary workplace sampling that identified
      the presence of 4-OPA, these studies examined the inflammatory and allergic
      responses to 4-OPA following both dermal and pulmonary exposure using a murine
      model. 4-OPA was tested in a combined local lymph node assay and identified to be
      an irritant and sensitizer. A Th1-mediated hypersensitivity response was
      supported by a positive response in the mouse ear swelling test. Pulmonary
      exposure to 4-OPA caused a significant elevation in nonspecific airway
      hyperreactivity, increased numbers of lung-associated lymphocytes and
      neutrophils, and increased interferon-gamma production by lung-associated lymph
      nodes. These results suggest that both dermal and pulmonary exposure to 4-OPA may
      elicit irritant and allergic responses and may help to explain some of the
      adverse health effects associated with poor indoor air quality.

PMID- 22403159
TI  - Formation, persistence, and identification of DNA adducts formed by the
      carcinogenic environmental pollutant o-anisidine in rats.
AB  - 2-Methoxyaniline (o-anisidine) is an industrial and environmental pollutant
      causing tumors of urinary bladder in rodents. Here, we investigated the formation
      and persistence of DNA adducts in the Wistar rat. Using the (32)P-postlabeling
      method, three o-anisidine-derived DNA adducts were found in several organs of
      rats treated with a total dose of 0.53 mg o-anisidine/kg body wt (0.15, 0.18, and
      0.2 mg/kg body wt ip in the first, second, and third day, respectively), of which
      the urinary bladder had the highest levels. At four posttreatment times (1 day,
      13 days, 10 weeks, and 36 weeks), DNA adducts in bladder, liver, kidney, and
      spleen of rats were analyzed to study their persistence. In all time points, the
      highest total adduct levels were found in urinary bladder (39 adducts per 10(7)
      nucleotides after 1 day and 15 adducts per 10(7) nucleotides after 36 weeks)
      where 39% adducts remained. In contrast to the urinary bladder, no persistence
      was detected in other organs. All three DNA adducts were identified as
      deoxyguanosine adducts. When deoxyguanosine was reacted with the oxidative
      metabolite of o-anisidine, N-(2-methoxyphenyl)hydroxylamine, three adducts could
      be separated by high-performance liquid chromatography (HPLC) and were identified
      by mass spectroscopy and/or nuclear magnetic resonance spectrometry. All adducts
      are products of the nitrenium/carbenium ions, the reactive species generated from
      N-(2-methoxyphenyl)hydroxylamine. The major adduct was identified to be N
      (deoxyguanosin-8-yl)-2-methoxyaniline. Using cochromatography on HPLC, this
      adduct was found to be identical to the major adduct generated by activation of o
      anisidine in vitro and in vivo.

PMID- 22403161
TI  - How are the costs of care for medical falls distributed? The costs of medical
      falls by component of cost, timing, and injury severity.
AB  - PURPOSE OF THE STUDY: To examine the components of cost that drive increased
      total costs after a medical fall over time, stratified by injury severity. DESIGN
      AND METHODS: We used 2004-2007 cost and utilization data for persons enrolled in
      an integrated care delivery system. We used a longitudinal cohort study design,
      where each individual provides 2-3 years of administrative data grouped into 3
      month intervals relative to an index date. We identified 8,969 medical fallers
      through International Classification of Diseases, 9th Revision, codes and E-Codes
      and used 8,956 nonfaller controls, identified through age and gender frequency
      matching. Total costs were partitioned into 7 components: inpatient, outpatient,
      emergency, radiology, pharmacy, postacute care, and "other." RESULTS: The large
      increase in costs after a hospitalized fall is mainly associated with inpatient
      and postacute care components. The spike in costs after a nonhospitalized fall is
      attributable to outpatient and "other" (e.g., ambulatory surgery or community
      health services) components. Hospitalized fallers' inpatient, emergency,
      postacute care, outpatient, and radiology costs are not always greater than those
      for nonhospitalized fallers. IMPLICATIONS: Components associated with increased
      costs after a medical fall vary over time and by injury severity. Future studies
      should compare if delivering certain acute and postacute health services improve
      health and reduce cost trajectories after a medical fall more than others.
      Additionally, since the older adult population and the problem of falls are
      growing, health care delivery systems should develop standardized methodology to
      monitor medical fall rates.

PMID- 22403162
TI  - Turning the lens inward: cultural competence and providers' values in health care
      decision making.
AB  - The population of older adults in the United States is growing in size and
      diversity, presenting challenges to health care providers and patients in the
      context of health care decision making (DM), including obtaining informed consent
      for treatment, advance care planning, and deliberations about end-of-life care
      options. Although existing literature addresses providers' need to attend to
      patients' cultural values and beliefs on these issues, less attention has been
      paid to how the corresponding values and beliefs of providers color the care they
      deliver and their assessments of older adults' DM capacity. The provider's
      challenge is to understand her own unacknowledged anxieties, prejudices, and
      fears around such charged issues as truth telling, individual agency, capacity,
      death and dying, and the value of life itself and address their impact on the
      delivery of care. A social constructivist perspective and the clinical concept of
      cultural countertransference are proposed as aides in achieving this awareness
      and improving care.

PMID- 22403163
TI  - The complex association between religious activities and functional limitations
      in older adults.
AB  - PURPOSE OF THE STUDY: To examine the longitudinal associations between 3
      dimensions of religious involvement-religious attendance, use of religious media,
      and private religious activities-and 3 domains of functional status-limitations
      in basic activities of daily living (ADL), instrumental activities of daily
      living (IADL), and mobility in older adults. DESIGN AND METHODS: Using the data
      from a survey of 2,924 adults aged 65+, with self-reported religious involvement
      and functional status collected at baseline, 3, 6, and 10 years postbaseline, we
      used repeated measures mixed models to predict functional change by religious
      status at the prior interview. RESULTS: Increased religious attendance was
      associated with fewer ADL, IADL, and mobility limitations 3-4 years later,
      controlling for demographic, health, and social variables as well as prior
      functional status. Neither use of religious media nor private religious
      activities was associated with functional change in controlled analyses. Use of
      religious media, however, was associated with developing more IADL and mobility
      limitations in uncontrolled analysis, suggesting a potential indirect
      association. IMPLICATIONS: Religious attendance may protect against decline in
      functional limitations in older adults. Clinicians may wish to consider the
      importance of attendance at services in preventing disability for those patients
      for whom religious involvement is important. Gerontologists may wish to include
      religious participation in their conceptual framework outlining risk factors for
      functional decline.

PMID- 22403164
TI  - OASIS connections: results from an evaluation study.
AB  - PURPOSE OF THE STUDY: The objectives of this study were to evaluate a community
      based basic computer and Internet training program designed for older adults,
      provide recommendations for program refinement, and gather preliminary
      information on program sustainability. DESIGN AND METHODS: The program was
      developed by the OASIS Institute, a nonprofit agency serving older adults and
      implemented in 4 cities by community trainers across the United States. One
      hundred and ninety-six adults aged 40-90 years were assigned to the training or a
      wait-list control group. Knowledge of computers and the Internet, attitudes
      toward computers, and computer/Internet use were assessed at baseline,
      posttraining, and 3 months posttraining. RESULTS: The program was successful in
      increasing the computer/Internet skills of the trainees. The data indicated a
      significant increase in computer and Internet knowledge and comfort with
      computers among those who received the training. Further, those who completed the
      course reported an increase in both computer and Internet use 3 months
      posttraining. IMPLICATIONS: The findings indicate that a community-based computer
      and Internet training program delivered by community instructors can be effective
      in terms of increasing computer and Internet skills and comfort with computer
      technology among older adults.

PMID- 22403165
TI  - Multiple trajectories of successful aging of older and younger cohorts.
AB  - PURPOSE: The purpose of this study was to apply group-based trajectory analysis
      to identify multiple successful aging trajectories by multiple indicators and to
      examine the factors related to successful aging among the elderly population in
      Taiwan. DESIGN AND METHODS: Nation-representative longitudinal data collected
      from 1993 to 2007 and consisting of 2 cohorts were used, and the trajectories of
      the following 6 successful aging indicators were analyzed: chronic diseases,
      physical function difficulties, depressive symptoms, social support, social
      participation, and economic satisfaction. RESULTS: Members of the cohorts fell
      into 4 groups: successful aging, usual aging (the older cohort)/insecure aging
      (the younger cohort), health declining, and care demanding. Successful aging
      trajectories reflected differences in self-rated health and life satisfaction.
      IMPLICATIONS: This study provides empirical findings of the heterogeneity of
      successful aging trajectories in multidimensional indicators.

PMID- 22403166
TI  - Neurodevelopmental outcomes in preterm infants: comparison of infants with and
      without diffuse excessive high signal intensity on MR images at near-term
      equivalent age.
AB  - PURPOSE: To compare the neurodevelopmental outcomes between preterm infants with
      diffuse excessive high signal intensity (DEHSI) and those without DEHSI on
      magnetic resonance (MR) images, in association with other white matter lesions.
      MATERIALS AND METHODS: This retrospective study was approved by the institutional
      review board, and requirement to obtain informed consent was waived. High-risk
      preterm infants (n = 126) who underwent screening brain MR imaging at near-term
      equivalent age were classified into two groups according to the presence of
      DEHSI. Bayley Scales of Infant Development-II, presence of cerebral palsy, and
      neurosensory impairment between 18 and 24 months of age were compared between the
      two groups. The associations of MR findings of other white matter lesions (cystic
      encephalomalacia, punctate lesions, loss of volume, ventricular dilatation, and
      delayed myelination) and subsequent outcomes were also analyzed. Outcome data
      were evaluated by using exact logistic regression analyses and Fisher exact test.
      RESULTS: DEHSI was present in 75% (95 of 126) of infants. Subsequent
      neurodevelopmental outcomes did not differ significantly between the two groups.
      Severe motor delay and cerebral palsy were more common in infants with both DEHSI
      and other white matter lesions as compared with infants with normal white matter
      (P = .001 and P < .001, respectively). Among other white matter lesions, cystic
      encephalomalacia (odds ratio, 19.6; 95% confidence interval: 1.3, 333.3) and
      punctate lesions (odds ratio, 90.9; 95% confidence interval: 6.4, 1000) were
      significant predictors of cerebral palsy. CONCLUSION: Although the incidence of
      DEHSI was high (75%) in preterm infants at near-term-equivalent age MR imaging,
      DEHSI was not predictive of following adverse outcomes. Cystic encephalomalacia
      and punctate lesions were more significant predictors of cerebral palsy.

PMID- 22403167
TI  - Femoral antetorsion: comparing asymptomatic volunteers and patients with
      femoroacetabular impingement.
AB  - PURPOSE: To assess the range of femoral antetorsion with magnetic resonance (MR)
      imaging in asymptomatic volunteers and patients with different subtypes of
      femoroacetabular impingement (FAI) because abnormal femoral antetorsion might be
      a contributing factor in the development of FAI. MATERIALS AND METHODS: This
      study was institutional review board approved; all individuals provided signed
      informed consent. Sixty-three asymptomatic volunteers and 63 patients with
      symptomatic FAI between age 20 and 50 years were matched for age and sex. They
      underwent standard MR imaging with two additional rapid transverse sequences over
      the proximal and distal femur for antetorsion measurement. Twenty volunteers
      underwent a second MR imaging examination in the same leg. Two readers
      independently measured femoral antetorsion. The time for the additional sequences
      was tabulated. Interobserver agreement was calculated; differences in antetorsion
      were assessed by using analysis of variance and the unpaired t test. RESULTS:
      Femoral antetorsion can be assessed with MR imaging in about 80 seconds, with
      high interobserver agreement (intraclass correlation coefficient [ICC] = 0.967)
      and high agreement between different MR examinations (ICC = 0.966). Women had a
      significantly larger antetorsion than men (P < .001 for both readers), and
      antetorsion of the left femur was significantly larger than that of the right
      femur (P = .01 for reader 1, P = .02 for reader 2). Overall, antetorsion was
      similar in volunteers and in patients for reader 1 (12.7 degrees  +/- 10.0
      [standard deviation] vs 12.6 degrees  +/- 9.8, respectively; P = .9) and reader 2
      (12.8 degrees  +/- 10.1 vs 13.5 degrees  +/- 9.8, respectively; P = .7). Femoral
      antetorsion was significantly higher in patients with pincer-type FAI than in
      those with cam-type FAI for reader 1 (18.3 degrees  +/- 9.8 vs 10.0 degrees  +/-
      9.1, P = .02) and reader 2 (18.7 degrees  +/- 10.5 vs 11.6 degrees  +/- 8.8, P =
      .04). CONCLUSION: Femoral antetorsion can be measured rapidly and with good
      reproducibility with MR imaging. Patients with pincer-type FAI had a
      significantly larger femoral antetorsion than patients with cam-type FAI.

PMID- 22403168
TI  - Gliomas: diffusion kurtosis MR imaging in grading.
AB  - PURPOSE: To assess the diagnostic accuracy of diffusion kurtosis magnetic
      resonance imaging parameters in grading gliomas. MATERIALS AND METHODS: The
      institutional review board approved this prospective study, and informed consent
      was obtained from all patients. Diffusion parameters-mean diffusivity (MD),
      fractional anisotropy (FA), mean kurtosis, and radial and axial kurtosis-were
      compared in the solid parts of 17 high-grade gliomas and 11 low-grade gliomas
      (P<.05 significance level, Mann-Whitney-Wilcoxon test, Bonferroni correction).
      MD, FA, mean kurtosis, radial kurtosis, and axial kurtosis in solid tumors were
      also normalized to the corresponding values in contralateral normal-appearing
      white matter (NAWM) and the contralateral posterior limb of the internal capsule
      (PLIC) after age correction and were compared among tumor grades. RESULTS: Mean,
      radial, and axial kurtosis were significantly higher in high-grade gliomas than
      in low-grade gliomas (P = .02, P = .015, and P = .01, respectively). FA and MD
      did not significantly differ between glioma grades. All values, except for axial
      kurtosis, that were normalized to the values in the contralateral NAWM were
      significantly different between high-grade and low-grade gliomas (mean kurtosis,
      P = .02; radial kurtosis, P = .03; FA, P = .025; and MD, P = .03). When values
      were normalized to those in the contralateral PLIC, none of the considered
      parameters showed significant differences between high-grade and low-grade
      gliomas. The highest sensitivity and specificity for discriminating between high
      grade and low-grade gliomas were found for mean kurtosis (71% and 82%,
      respectively) and mean kurtosis normalized to the value in the contralateral NAWM
      (100% and 73%, respectively). Optimal thresholds for mean kurtosis and mean
      kurtosis normalized to the value in the contralateral NAWM for differentiating
      high-grade from low-grade gliomas were 0.52 and 0.51, respectively. CONCLUSION:
      There were significant differences in kurtosis parameters between high-grade and
      low-grade gliomas; hence, better separation was achieved with these parameters
      than with conventional diffusion imaging parameters.

PMID- 22403169
TI  - Nasopharyngeal mucosa and adenoids: appearance at MR imaging.
AB  - PURPOSE: To document the magnetic resonance (MR) imaging appearances of benign
      nasopharyngeal mucosa and adenoids and to correlate quantitative thickness
      measurements with histologic findings from nasopharyngeal biopsy specimens.
      MATERIALS AND METHODS: MR imaging studies and nasopharyngeal biopsy specimens
      were analyzed retrospectively in 100 adults (51 men, 49 women) with benign
      histologic findings; local institutional review board approval and informed
      consent had been obtained as part of a previous imaging study. At T1-weighted
      gadolinium-enhanced MR imaging, the nasopharyngeal roof and adenoid was
      classified as follows: 1, pencil thin, less than 3 mm; 2, smooth thickening, 3 mm
      or larger; 3, small tags or stripes; or 4, focal adenoid mass with a vertical
      striped appearance. The posterior and lateral walls were classified as follows:
      pattern 1, pencil thin, less than 3 mm; pattern 2, mild thickening, 3 mm or
      larger with moderate enhancement; or pattern 3, thickening with hypoenhancement
      along the posterior wall. The frequency of these patterns, as well as cysts,
      symmetry, and pharyngeal recess patency, were documented. Wall thickness was
      measured and correlated with age, sex, and histologic findings from biopsy
      specimens by using Spearman rank correlation and Mann-Whitney U tests. RESULTS:
      In 100 patients, roof patterns 1-4 were identified in 16 (16%), seven (7%), 33
      (33%), and 44 (44%); posterior and lateral wall patterns 1-3 were identified in
      20 (20%), 55 (55%), and 25 (25%) patients. Symmetry was identified in 95 (95%)
      patients, cysts in 41 (41%) patients, and pharyngeal recess patency was
      identified in 24 (12%) of 200 sides. Roof including adenoid thickness was higher
      in men (P = .05) and correlated inversely with age (P <.01). In 62 (62%) of 100
      patients, biopsy specimens contained lymphoid follicles. Roof including adenoid
      (P = .01) and posterior wall (P = .03) thickness at MR imaging was higher if
      follicles were identified in biopsy specimens. CONCLUSION: Nasopharyngeal
      hyperplasia has typical MR imaging appearances, including stripes in adenoid
      bulges and symmetry, which may be useful to differentiate this condition from
      nasopharyngeal malignancy.

PMID- 22403170
TI  - Volumetric MR-guided high-intensity focused ultrasound ablation with a one-layer
      strategy to treat large uterine fibroids: initial clinical outcomes.
AB  - PURPOSE: To evaluate initial clinical outcomes of volumetric magnetic resonance
      (MR)-guided high-intensity focused ultrasound (HIFU) ablation by using a one
      layer strategy to treat large (>10 cm in diameter) uterine fibroids, with
      investigation of the correlation between effectiveness of the one-layer strategy
      and dynamic contrast material-enhanced (DCE) MR parameters. MATERIALS AND
      METHODS: Institutional review board approval and informed consent were obtained.
      Twenty-seven women (mean age, 44.5 years) with 27 large uterine fibroids (mean
      diameter, 11.3 cm +/- 1.4 [standard deviation] [range, 10.1-16.0 cm]; fibroid
      volume, 502.5 mL +/- 214.3 [range, 253.8-1184.0 mL]) underwent volumetric MR
      guided HIFU ablation with a one-layer strategy. (All treatment cells were placed
      in one coronal plane at a depth of half to anterior two-thirds of the
      anteroposterior dimension of fibroids.) Treatment time, immediate nonperfused
      volume (NPV), and effectiveness of a one-layer strategy (ratio of immediate NPV
      to total volume of treatment cells planned) correlating with baseline DCE MR
      parameters (volume transfer constant [K(trans)], fractional extravascular
      extracellular space, and fractional blood plasma volume [Pearson correlation
      test]), complications, 3-month follow-up volumes, and symptom severity score
      (SSS) changes (paired t test) were assessed retrospectively. RESULTS: All
      treatments showed technical success in one session (mean treatment time, 166.2
      minutes +/- 38.9). NPV was 301.3 mL +/- 119.1, which was 64.2% +/- 19.9 (<50%, n
      = 4; >= 50%, n = 23) of fibroid volume. Ratio of immediate NPV to total volume of
      treatment cells (1.79 +/- 0.61) negatively correlated with DCE MR imaging
      K(trans) values (r = -0.426, P = .017). Minor complications occurred in five
      patients (18.5% [thermal injury of abdominal wall, n = 3; 30-day leg numbness, n
      = 1; cystitis, n = 1]). At 3-month follow-up (n = 18), mean SSS had decreased
      from 37.4 at baseline to 24.0 (P < .001), and volume reduction ratio was 0.64 +/-
      0.15 (P < .001). CONCLUSION: Volumetric MR-guided HIFU ablation with a one-layer
      strategy is safe and effective for treatment of large uterine fibroids.
      Effectiveness of this strategy showed a significant negative correlation with
      K(trans) values at baseline DCE MR imaging.

PMID- 22403171
TI  - Placement of marker coils at biopsy: usefulness in the localization of poorly
      visualized renal neoplasms for subsequent CT-guided radiofrequency ablation.
AB  - PURPOSE: To determine whether placement of marking coils at biopsy of small renal
      neoplasms to facilitate localization at subsequent radiofrequency (RF) ablation
      is safe and can reduce fluoroscopy time during the ablative procedure. MATERIALS
      AND METHODS: This retrospective study was approved by the hospital institutional
      review board and was compliant with HIPAA. The requirement to obtain informed
      consent was waived. A search of the renal RF ablation database (235 patients)
      identified 23 consecutive patients who had a marking coil placed at biopsy of a
      renal neoplasm (coil group) and 23 patients who did not have a marking coil
      placed at biopsy (control group). The patients were matched for tumor
      characteristics, including size, parenchymal position, location in the kidney,
      and laterality. All patients underwent subsequent RF ablation. The authors
      compared computed tomographic (CT) fluoroscopy times and technical success rates
      between the two groups. Statistical analyses were performed by using a single
      tailed paired t test for comparison of CT fluoroscopy times, a two-tailed paired
      t test for comparison of age and tumor size, and a single-tailed McNemar test for
      comparison of the technical success rate of ablation. RESULTS: The mean CT
      fluoroscopy time for the RF ablation procedure was 28 seconds +/- 11.7 (standard
      deviation) for the coil group and 66 seconds +/- 85.8 for the control group (P =
      .025). There was no significant difference in the technical success rates of
      renal RF ablation. CONCLUSION: For small renal neoplasms that are poorly
      visualized at unenhanced CT, placement of a metallic marking coil at biopsy
      facilitates tumor localization, thus reducing CT fluoroscopy time and radiation
      dose for subsequent RF ablation procedures.

PMID- 22403172
TI  - Pax6 is crucial for beta-cell function, insulin biosynthesis, and glucose-induced
      insulin secretion.
AB  - The Pax6 transcription factor is crucial for endocrine cell differentiation and
      function. Indeed, mutations of Pax6 are associated with a diabetic phenotype and
      a drastic decrease of insulin-positive cell number. Our aim was to better define
      the beta-cell Pax6 transcriptional network and thus provide further information
      concerning the role of Pax6 in beta-cell function. We developed a Pax6-deficient
      model in rat primary beta-cells with specific small interfering RNA leading to a
      75% knockdown of Pax6 expression. Through candidate gene approach, we confirmed
      that Pax6 controls the mRNA levels of the insulin 1 and 2, Pdx1, MafA, GLUT2, and
      PC1/3 genes in beta-cells. Importantly, we identified new Pax6 target genes
      coding for GK, Nkx6.1, cMaf, PC2, GLP-1R and GIPR which are all involved in beta
      cell function. Furthermore, we demonstrated that Pax6 directly binds and
      activates specific elements on the promoter region of these genes. We also
      demonstrated that Pax6 knockdown led to decreases in insulin cell content, in
      insulin processing, and a specific defect of glucose-induced insulin secretion as
      well as a significant reduction of GLP-1 action in primary beta-cells. Our
      results strongly suggest that Pax6 is crucial for beta-cells through
      transcriptional control of key genes coding for proteins that are involved in
      insulin biosynthesis and secretion as well as glucose and incretin actions on
      beta-cells. We provide further evidence that Pax6 represents a key element of
      mature beta-cell function.

PMID- 22403173
TI  - Absence of myocardial thyroid hormone inactivating deiodinase results in
      restrictive cardiomyopathy in mice.
AB  - Cardiac injury induces myocardial expression of the thyroid hormone inactivating
      type 3 deiodinase (D3), which in turn dampens local thyroid hormone signaling.
      Here, we show that the D3 gene (Dio3) is a tissue-specific imprinted gene in the
      heart, and thus, heterozygous D3 knockout (HtzD3KO) mice constitute a model of
      cardiac D3 inactivation in an otherwise systemically euthyroid animal. HtzD3KO
      newborns have normal hearts but later develop restrictive cardiomyopathy due to
      cardiac-specific increase in thyroid hormone signaling, including myocardial
      fibrosis, impaired myocardial contractility, and diastolic dysfunction. In wild
      type littermates, treatment with isoproterenol-induced myocardial D3 activity and
      an increase in the left ventricular volumes, typical of cardiac remodeling and
      dilatation. Remarkably, isoproterenol-treated HtzD3KO mice experienced a further
      decrease in left ventricular volumes with worsening of the diastolic dysfunction
      and the restrictive cardiomyopathy, resulting in congestive heart failure and
      increased mortality. These findings reveal crucial roles for Dio3 in heart
      function and remodeling, which may have pathophysiologic implications for human
      restrictive cardiomyopathy.

PMID- 22403174
TI  - Revisiting and questioning functional rescue between dimerized LH receptor
      mutants.
AB  - The glycoprotein hormone receptors are G protein-coupled receptors containing a
      large extracellular domain fused to a prototypical serpentine domain. cis
      activation occurs when binding of hormone to the extracellular domain stabilizes
      the serpentine domain in an active conformation. Studies by others suggested that
      these receptors can also signal by trans-activation, where hormone binding to one
      receptor protomer activates the serpentine domain of an associated protomer, as
      documented by the partial rescue of hormone-dependent signaling when a binding
      defective mutant is coexpressed with a signaling defective mutant. However, our
      characterizations of several LH receptor (LHR) mutants used in previous studies
      differ markedly from those originally reported. Also, when examining a pair of
      LHR mutants previously shown to functionally rescue in vitro as well as in vivo,
      in addition to finding that the properties of the individual mutants differ
      significantly from those originally described, we determined that when this pair
      of mutants was coexpressed in vitro, quantitative analyses did not indicate
      functional rescue. Additional data are presented that provide a plausible
      alternate explanation for the apparent in vivo trans-activation that was
      reported. Finally, using LHR mutants that we have documented to be expressed at
      the cell surface but to lack human chorionic gonadotropin binding activity or to
      be severely impaired in their ability to activate Gs, we did not observe
      functional rescue of human chorionic gonadotropin-stimulated cAMP when the
      mutants were coexpressed, even though bioluminescence resonance energy transfer
      analyses confirmed that the coexpressed mutants formed dimers. Taken altogether,
      our data substantively question the concept of functional rescue between LHR
      mutants.

PMID- 22403175
TI  - Central role for PELP1 in nonandrogenic activation of the androgen receptor in
      prostate cancer.
AB  - The ability of 17beta-estradiol (E2) to regulate the proliferation of prostate
      cancer (PCa) cells in the absence of androgen is poorly understood. Here, we show
      the predominant estrogen receptor (ER) isoform expressed in PCa specimens and
      cell lines is ERbeta. Our data indicate that E2 induces the formation of a
      complex between androgen receptor (AR), ERbeta, and a proline-, glutamic acid-,
      and leucine-rich cofactor protein 1 (PELP1) in PCa cells. This protein complex is
      formed on AR's cognate DNA-responsive elements on the promoter in response to E2.
      Formation of this complex enables the transcription of AR-responsive genes in
      response to E2. Knockdown of PELP1, AR, or ERbeta blocks the assembly of this
      complex, blocks E2-induced genomic activation of AR-regulated genes, and blocks
      E2-stimulated proliferation of PCa cells. Overall, this study shows that PELP1
      may enable E2-induced AR signaling by forming a protein complex between AR,
      ERbeta, and PELP1 on the DNA, leading to the proliferation of PCa cells in the
      absence of androgen. PELP1 may bridge the signal between E2 bound to ERbeta and
      AR and thus allow for cross talk between these steroid receptors. These data
      suggest a novel mechanism of AR activation in the absence of androgens in PCa
      cells. Our data indicate that disruption of the complex between AR and PELP1 may
      be a viable therapeutic strategy in advanced PCa.

PMID- 22403176
TI  - Rare cause of upper gastrointestinal bleeding in a 27-year-old male patient.

PMID- 22403177
TI  - A segmentation clock with two-segment periodicity in insects.
AB  - Vertebrate segmentation relies on a mechanism characterized by oscillating gene
      expression. Whether this mechanism is used by other segmented animals has been
      controversial. Rigorous proof of cyclic expression during arthropod segmentation
      has been lacking. We find that the segmentation gene odd-skipped (Tc-odd)
      oscillates with a two-segment periodicity in the beetle Tribolium castaneum. By
      bisecting embryos and culturing the two halves over different time intervals, we
      demonstrate that Tc-odd cycles with a period of about 95 minutes at 30 degrees C.
      Using live imaging and cell tracking in green fluorescent protein-expressing
      embryos, we can exclude that cell movements explain this dynamic expression. Our
      results show that molecular oscillators represent a common feature of
      segmentation in divergent animals and help reconcile the contrasting paradigms of
      insect and vertebrate segmentation.

PMID- 22403179
TI  - A 2D quantum walk simulation of two-particle dynamics.
AB  - Multidimensional quantum walks can exhibit highly nontrivial topological
      structure, providing a powerful tool for simulating quantum information and
      transport systems. We present a flexible implementation of a two-dimensional (2D)
      optical quantum walk on a lattice, demonstrating a scalable quantum walk on a
      nontrivial graph structure. We realized a coherent quantum walk over 12 steps and
      169 positions by using an optical fiber network. With our broad spectrum of
      quantum coins, we were able to simulate the creation of entanglement in bipartite
      systems with conditioned interactions. Introducing dynamic control allowed for
      the investigation of effects such as strong nonlinearities or two-particle
      scattering. Our results illustrate the potential of quantum walks as a route for
      simulating and understanding complex quantum systems.

PMID- 22403178
TI  - Mapping the core of the Arabidopsis circadian clock defines the network structure
      of the oscillator.
AB  - In many organisms, the circadian clock is composed of functionally coupled
      morning and evening oscillators. In Arabidopsis, oscillator coupling relies on a
      core loop in which the evening oscillator component TIMING OF CAB EXPRESSION 1
      (TOC1) was proposed to activate a subset of morning-expressed oscillator genes.
      Here, we show that TOC1 does not function as an activator but rather as a general
      repressor of oscillator gene expression. Repression occurs through TOC1 rhythmic
      association to the promoters of the oscillator genes. Hormone-dependent induction
      of TOC1 and analysis of RNA interference plants show that TOC1 prevents the
      activation of morning-expressed genes at night. Our study overturns the
      prevailing model of the Arabidopsis circadian clock, showing that the morning and
      evening oscillator loops are connected through the repressing activity of TOC1.

PMID- 22403180
TI  - Gap junctions compensate for sublinear dendritic integration in an inhibitory
      network.
AB  - Electrically coupled inhibitory interneurons dynamically control network
      excitability, yet little is known about how chemical and electrical synapses
      regulate their activity. Using two-photon glutamate uncaging and dendritic patch
      clamp recordings, we found that the dendrites of cerebellar Golgi interneurons
      acted as passive cables. They conferred distance-dependent sublinear synaptic
      integration and weakened distal excitatory inputs. Gap junctions were present at
      a higher density on distal dendrites and contributed substantially to membrane
      conductance. Depolarization of one Golgi cell increased firing in its neighbors,
      and inclusion of dendritic gap junctions in interneuron network models enabled
      distal excitatory synapses to drive network activity more effectively. Our
      results suggest that dendritic gap junctions counteract sublinear dendritic
      integration by enabling excitatory synaptic charge to spread into the dendrites
      of neighboring inhibitory interneurons.

PMID- 22403181
TI  - Extrachromosomal microDNAs and chromosomal microdeletions in normal tissues.
AB  - We have identified tens of thousands of short extrachromosomal circular DNAs
      (microDNA) in mouse tissues as well as mouse and human cell lines. These
      microDNAs are 200 to 400 base pairs long, are derived from unique nonrepetitive
      sequence, and are enriched in the 5'-untranslated regions of genes, exons, and
      CpG islands. Chromosomal loci that are enriched sources of microDNA in the adult
      brain are somatically mosaic for microdeletions that appear to arise from the
      excision of microDNAs. Germline microdeletions identified by the "Thousand
      Genomes" project may also arise from the excision of microDNAs in the germline
      lineage. We have thus identified a previously unknown DNA entity in mammalian
      cells and provide evidence that their generation leaves behind deletions in
      different genomic loci.

PMID- 22403182
TI  - Canakinumab induces remission in a patient with resistant familial Mediterranean
      fever.

PMID- 22403183
TI  - Microparticles as mediators and biomarkers of rheumatic disease.
AB  - Microparticles (MPs) are small membrane-bound vesicles that arise from activated
      and dying cells and enter the blood to display pro-inflammatory and pro
      thrombotic activities. MPs are 0.1-1.0 MUm in size and incorporate nuclear,
      cytoplasmic and membrane molecules as they detach from cells. This process can
      occur with cell activation as well as cell death, with particles likely
      corresponding to blebs that form on the cell surface during apoptosis. To measure
      particle expression, flow cytometry allows determination of particle numbers
      based on size as well as surface markers that denote the cell of origin; platelet
      MPs are usually the most abundant type in blood. As shown in in vitro and in vivo
      systems, MPs can promote inflammation and thrombosis resulting from their content
      of cytokines like IL-1 and pro-coagulant molecules like tissue factor. Certain
      particle types can be anti-inflammatory, however, suggesting a range of
      immunomodulatory activities depending on the cell of origin. Studies on patients
      with a wide range of rheumatic disease show increased MP numbers in blood, with
      platelet and endothelial particles associated with vascular manifestations;
      increased numbers of particles also occur in the joint fluid where they may drive
      cytokine production and activate synoviocytes. In autoimmune diseases such as SLE
      and RA, MPs may also contribute to disease pathogenesis by the formation of
      immune complexes. MPs thus represent novel subcellular structures that can impact
      on the pathogenesis of rheumatic disease and serve as biomarkers of underlying
      cellular disturbances.

PMID- 22403184
TI  - Statistical colocalization of monocyte gene expression and genetic risk variants
      for type 1 diabetes.
AB  - One mechanism by which disease-associated DNA variation can alter disease risk is
      altering gene expression. However, linkage disequilibrium (LD) between variants,
      mostly single-nucleotide polymorphisms (SNPs), means it is not sufficient to show
      that a particular variant associates with both disease and expression, as there
      could be two distinct causal variants in LD. Here, we describe a formal
      statistical test of colocalization and apply it to type 1 diabetes (T1D)
      associated regions identified mostly through genome-wide association studies and
      expression quantitative trait loci (eQTLs) discovered in a recently determined
      large monocyte expression data set from the Gutenberg Health Study (1370
      individuals), with confirmation sought in an additional data set from the
      Cardiogenics Transcriptome Study (558 individuals). We excluded 39 out of 60
      overlapping eQTLs in 49 T1D regions from possible colocalization and identified
      21 coincident eQTLs, representing 21 genes in 14 distinct T1D regions. Our
      results reflect the importance of monocyte (and their derivatives, macrophage and
      dendritic cell) gene expression in human T1D and support the candidacy of several
      genes as causal factors in autoimmune pancreatic beta-cell destruction, including
      AFF3, CD226, CLECL1, DEXI, FKRP, PRKD2, RNLS, SMARCE1 and SUOX, in addition to
      the recently described GPR183 (EBI2) gene.

PMID- 22403186
TI  - Genome mining reveals the presence of a conserved gene cluster for the
      biosynthesis of ergot alkaloid precursors in the fungal family Arthrodermataceae.
AB  - Genome sequence analysis of different fungi of the family Arthrodermataceae
      revealed the presence of a gene cluster consisting of five genes with high
      sequence similarity to those involved in the early common steps of ergot alkaloid
      biosynthesis in Aspergillus fumigatus and Claviceps purpurea. To provide evidence
      that this cluster is involved in ergot alkaloid biosynthesis, the gene ARB_04646
      of the fungus Arthroderma benhamiae was cloned into pQE60 and expressed in
      Escherichia coli. Enzyme assays with the soluble tetrameric His(6)-tagged protein
      proved unequivocally that the deduced gene product, here termed ChaDH, catalysed
      the oxidation of chanoclavine-I in the presence of NAD(+), resulting in the
      formation of chanoclavine-I aldehyde. The enzyme product was unequivocally proven
      by NMR and MS analyses. Therefore, ChaDH functions as a chanoclavine-I
      dehydrogenase. K(m) values for chanoclavine-I and NAD(+) were 0.09 and 0.36 mM,
      respectively. Turnover number was 0.76 s(-1).

PMID- 22403185
TI  - Impaired neurotransmission in ether lipid-deficient nerve terminals.
AB  - Isolated defects of ether lipid (EL) biosynthesis in humans cause rhizomelic
      chondrodysplasia punctata type 2 and type 3, serious peroxisomal disorders. Using
      a previously described mouse model [Rodemer, C., Thai, T.P., Brugger, B.,
      Kaercher, T., Werner, H., Nave, K.A., Wieland, F., Gorgas, K., and Just, W.W.
      (2003) Inactivation of ether lipid biosynthesis causes male infertility, defects
      in eye development and optic nerve hypoplasia in mice. Hum. Mol. Genet., 12, 1881
      1895], we investigated the effect of EL deficiency in isolated murine nerve
      terminals (synaptosomes) on the pre-synaptic release of the neurotransmitters
      (NTs) glutamate and acetylcholine. Both Ca(2+)-dependent exocytosis and Ca(2+)
      independent efflux of the transmitters were affected. EL-deficient synaptosomes
      respire at a reduced rate and exhibit a lowered adenosin-5'
      triphosphate/adenosine diphosphate (ATP/ADP) ratio. Consequently, ATP-driven
      processes, such as synaptic vesicle cycling and maintenance of Na(+), K(+) and
      Ca(2+) homeostasis, might be disturbed. Analyzing reactive oxygen species in EL
      deficient neural and non-neural tissues revealed that plasmalogens (PLs), the
      most abundant EL species in mammalian central nervous system, considerably
      contribute to the generation of the lipid peroxidation product malondialdehyde.
      Although EL-deficient tissue contains less lipid peroxidation products,
      fibroblasts lacking ELs are more susceptible to induced oxidative stress. In
      summary, these results suggest that due to the reduced energy state of EL
      deficient tissue, the Ca(2+)-independent efflux of NTs increases while the Ca(2+)
      dependent release declines. Furthermore, lack of PLs is mainly compensated for by
      an increase in the concentration of phosphatidylethanolamine and results in a
      significantly lowered level of lipid peroxidation products in the brain cortex
      and cerebellum.

PMID- 22403187
TI  - A Toll/interleukin (IL)-1 receptor domain protein from Yersinia pestis interacts
      with mammalian IL-1/Toll-like receptor pathways but does not play a central role
      in the virulence of Y. pestis in a mouse model of bubonic plague.
AB  - The Toll/interleukin (IL)-1 receptor (TIR) domain is an essential component of
      eukaryotic innate immune signalling pathways. Interaction between TIR domains
      present in Toll-like receptors and associated adaptors initiates and propagates
      an immune signalling cascade. Proteins containing TIR domains have also been
      discovered in bacteria. Studies have subsequently shown that these proteins are
      able to modulate mammalian immune signalling pathways dependent on TIR
      interactions and that this may represent an evasion strategy for bacterial
      pathogens. Here, we investigate a TIR domain protein from the highly virulent
      bacterium Yersinia pestis, the causative agent of plague. When overexpressed in
      vitro this protein is able to downregulate IL-1beta- and LPS-dependent signalling
      to NFkappaB and to interact with the TIR adaptor protein MyD88. This interaction
      is dependent on a single proline residue. However, a Y. pestis knockout mutant
      lacking the TIR domain protein was not attenuated in virulence in a mouse model
      of bubonic plague. Minor alterations in the host cytokine response to the mutant
      were indicated, suggesting a potential subtle role in pathogenesis. The Y. pestis
      mutant also showed increased auto-aggregation and reduced survival in high
      salinity conditions, phenotypes which may contribute to pathogenesis or survival.

PMID- 22403188
TI  - Hydrogenase activity in the foodborne pathogen Campylobacter jejuni depends upon
      a novel ABC-type nickel transporter (NikZYXWV) and is SlyD-independent.
AB  - Campylobacter jejuni is a human pathogen of worldwide significance. It is
      commensal in the gut of many birds and mammals, where hydrogen is a readily
      available electron donor. The bacterium possesses a single membrane-bound,
      periplasmic-facing NiFe uptake hydrogenase that depends on the acquisition of
      environmental nickel for activity. The periplasmic binding protein Cj1584 (NikZ)
      of the ATP binding cassette (ABC) transporter encoded by the cj1584c-cj1580c
      (nikZYXWV) operon in C. jejuni strain NCTC 11168 was found to be nickel-repressed
      and to bind free nickel ions with a submicromolar K(d) value, as measured by
      fluorescence spectroscopy. Unlike the Escherichia coli NikA protein, NikZ did not
      bind EDTA-chelated nickel and lacks key conserved residues implicated in
      metallophore interaction. A C. jejuni cj1584c null mutant strain showed an
      approximately 22-fold decrease in intracellular nickel content compared with the
      wild-type strain and a decreased rate of uptake of (63)NiCl(2). The inhibition of
      residual nickel uptake at higher nickel concentrations in this mutant by hexa
      ammine cobalt (III) chloride or magnesium ions suggests that low-affinity uptake
      occurs partly through the CorA magnesium transporter. Hydrogenase activity was
      completely abolished in the cj1584c mutant after growth in unsupplemented media,
      but was fully restored after growth with 0.5 mM nickel chloride. Mutation of the
      putative metallochaperone gene slyD (cj0115) had no effect on either
      intracellular nickel accumulation or hydrogenase activity. Our data reveal a
      strict dependence of hydrogenase activity in C. jejuni on high-affinity nickel
      uptake through an ABC transporter that has distinct properties compared with the
      E. coli Nik system.

PMID- 22403190
TI  - A domino-like chlamydial attachment process: concurrent Parachlamydia
      acanthamoebae attachment to amoebae is required for several amoebal released
      molecules and serine protease activity.
AB  - Parachlamydia acanthamoebae is an obligate intracellular bacterium that infects
      free-living amoebae (Acanthamoeba), and is a potential human pathogen associated
      with hospital-acquired pneumonia. The attachment mechanism of this bacteria to
      host cells is crucial in bacterial pathogenesis, yet remains undetermined. Hence,
      we obtained monoclonal antibodies (mAbs) specific to either P. acanthamoebae or
      amoebae in an attempt to elucidate the attachment mechanism involved. Hybridomas
      of 954 clones were assessed, and we found that four mAbs (mAb38, mAb300, mAb311,
      mAb562) that were reactive to the amoebae significantly inhibited bacterial
      attachment. All mAbs recognized amoebal released molecules, and mAb311 also
      recognized the amoebal surface. mAbs reacted with the bacteria not only within
      amoebae, but also when they were released from amoebae (except mAb311).
      Furthermore, a serine protease inhibitor had an inhibitory effect on the
      bacterial attachment to amoebae, although none of the mAbs had any synergistic
      effect on the inhibition of attachment by the protease inhibitor. Taken together,
      we conclude that concurrent P. acanthoamebae attachment to amoebae is required
      for several amoebal released molecules and serine protease activity, implying the
      existence of a complicated host-parasite relationship.

PMID- 22403189
TI  - Variation at the capsule locus, cps, of mistyped and non-typable Streptococcus
      pneumoniae isolates.
AB  - The capsule polysaccharide locus (cps) is the site of the capsule biosynthesis
      gene cluster in encapsulated Streptococcus pneumoniae. A set of pneumococcal
      samples and non-pneumococcal streptococci from Denmark, the Gambia, the
      Netherlands, Thailand, the UK and the USA were sequenced at the cps locus to
      elucidate serologically mistyped or non-typable isolates. We identified a novel
      serotype 33B/33C mosaic capsule cluster and previously unseen serotype 22F
      capsule genes, disrupted and deleted cps clusters, the presence of aliB and nspA
      genes that are unrelated to capsule production, and similar genes in the non
      pneumococcal samples. These data provide greater understanding of diversity at a
      locus which is crucial to the antigenic diversity of the pathogen and current
      vaccine strategies.

PMID- 22403191
TI  - Declining numbers of family physicians are caring for children.
AB  - Despite continued growth of the primary care workforce, profound maldistribution
      persists among providers available for the care of children. Family physicians
      (FPs) spend, on average, approximately 10% of their total practice time caring
      for children; however, given that, among physician specialties, FPs are
      geographically distributed most evenly across the US population, the self
      reported decline in the share of FPs caring for children should be disturbing to
      policymakers, especially with the looming insurance expansion in 2014.

PMID- 22403192
TI  - Family physicians closing their doors to children: considering the implications.

PMID- 22403193
TI  - Share the CareTM: building teams in primary care practices.

PMID- 22403194
TI  - Essentials for great teams: trust, diversity, communication ... and joy.

PMID- 22403195
TI  - More black box to explore: how quality improvement collaboratives shape practice
      change.
AB  - BACKGROUND: Quality improvement collaboratives (QICs) are used extensively to
      promote quality improvement in health care. Evidence of their effectiveness is
      limited, prompting calls to "open up the black box" to better understand how and
      why such collaboratives work. METHODS: We selected a cohort of 5 primary care
      practices that participated in a 6-month intervention study aimed at improving
      colorectal cancer screening rates. Using an immersion/crystallization technique,
      we analyzed qualitative data that included audio recordings and field notes of
      QICs and practice-based team meetings. RESULTS: Three themes emerged from our
      analysis: (1) practice staff became empowered through and drew on the QICs to
      advance change efforts in the face of leader/physician resistance; (2) a mix of
      content and media in the QIC program was important for reaching all participants;
      (3) resources offered at the QIC did little to spur practice change efforts.
      CONCLUSION: QICs offer a potentially powerful way of disseminating health care
      innovations through enhanced strategies for learning and change. Creating
      collaborative environments in which diverse participants learn, listen, reflect,
      and share together can enable them to take back to their own organizations key
      messages and change strategies that benefit them the most.

PMID- 22403196
TI  - Impact of a Wellness Portal on the delivery of patient-centered preventive care.
AB  - BACKGROUND: The objective of this study was to determine the impact of the
      Wellness Portal--a novel, web-based patient portal that focuses on wellness,
      prevention, and longitudinal health--on the delivery of patient-centered
      preventive care by examining the behavior and experiences of both patients and
      primary care clinicians and the degree to which recommended services were
      individualized and provided. METHODS: We conducted a 3-year, systematic portal
      development and testing study, which included a 6-month feasibility and
      acceptability pilot in 2 primary care practices followed by a 12-month cluster
      randomized controlled trial in 8 clinician practices (4 in each study group).
      Descriptive and bivariate analyses were conducted to compare service delivery
      between intervention and control arms. RESULTS: Ninety percent of patients in the
      pilot study found the portal easy to use, 83% found it to be a valuable resource,
      and 80% said that it facilitated their participation in their own care. The
      cluster randomized controlled trial included 422 adults 40 to 75 years of age and
      the parents of 116 children 2 to 5 years of age. Seventy three percent of
      patients used the portal during the study. Both patient activation (measured via
      the 13-item Patient Activation Measure) and participants' perception of patient
      centeredness of care (measured via the Consumer Assessment of Healthcare
      Providers and Systems instrument) increased significantly in the portal group
      compared with control (P = .0014 and P = .037, respectively). A greater
      proportion of portal users received all recommended preventive services (84.4%
      intervention vs 67.6% control; P < .0001); took low-dose aspirin, if indicated
      (78.6% intervention vs 52.3% control; P < .0001); and received Pneumovax because
      of chronic health conditions (82.5% vs 53.9%; P < .0001) and age (86.3% vs 44.6%;
      P < .0001), despite having fewer visits over the study period compared with those
      in the control group (average of 2.9 vs 4.3 visits; P < .0001). Children in the
      intervention group received 95.5% of all recommended immunizations compared with
      87.2% in the control group (P = .044). CONCLUSIONS: A comprehensive patient
      portal integrated into the regular process of primary care can increase the
      patient-centeredness of care, improve patient activation, enhance the delivery of
      both age- and risk factor-appropriate preventive services, and promote the
      utilization of web-based personal health records.

PMID- 22403197
TI  - Difficulties encountered in collaborative care: logistics trumps desire.
AB  - INTRODUCTION: This study examines the development of collaborative relationships
      between family physicians (FPs) and Anticipatory And Preventative Team Care
      (APTCare) team members providing care to medically complex patients who have been
      identified as at-risk for negative health outcomes. METHODS: We undertook a
      qualitative study of a primary health care intervention in a family practice.
      Interviews were held with FPs and ATPCare intervention nurse practitioners (NPs)
      and pharmacists. Focus groups were conducted and a survey was administered to
      participating FPs, NPs, and pharmacists. NPs and pharmacists maintained a log
      recording their tasks and moments of collaboration. RESULTS: Scheduling demands
      rendered face-to-face collaboration difficult, leaving the team to rely on
      technological tools to keep in touch. Limited space meant the APTCare team had to
      work out of a downstairs office, limiting informal interactions with the
      practitioners on the main level. CONCLUSIONS: We demonstrate that the
      difficulties inherent in collaborative care are independent of the patient
      population being cared for. Regardless of the patient population and sector of
      health care, developing collaborative relationships and learning to work
      collaboratively is difficult and takes time. What many of these teams need is
      ongoing support and education about how to make these collaborative care
      practices work.

PMID- 22403198
TI  - Emotional impact of patient safety incidents on family physicians and their
      office staff.
AB  - OBJECTIVE: The objective of this study was to investigate the emotional responses
      and coping strategies that family physicians and their office staff reported in
      response to a patient safety incident. METHOD: Two questions contained in a
      patient safety incident report developed for a study of patient safety in family
      practice were analyzed. The questions asked reporters to indicate their emotional
      response to a patient safety incident and how they coped with it. A total of 264
      confidential patient safety incident reports collected from September 2007 to
      August 2010 were analyzed. RESULTS: An emotional response was reported on 82.4%
      of reports. Of those reports on which an emotional response was reported, a
      coping strategy was reported on 62.8%. The top 4 reported emotional responses
      were frustration (48.3%), embarrassment (31.5%), anger (12.6%), and guilt
      (10.1%). Physicians reported an emotional response more often than clinic staff.
      An emotional response was reported more often when there was a possibility of
      harm. Coping strategies were reported as follows: 52% talked to someone about the
      incident, 37.2% did nothing in response to the incident, 17.9% told the patient
      about the incident, and 3.6% did something else. Female physicians reported using
      coping strategies less often than male physicians. A coping strategy was reported
      more often when there was a possibility of harm. CONCLUSIONS: All members of the
      health care team report experiencing emotions related to patient safety incidents
      in their practice. Incidents with minor or no harm still invoked emotional
      responses from the providers. It is important to understand the impact that
      patient safety incidents have on the medical clinic as a whole.

PMID- 22403199
TI  - Reducing utilization by uninsured frequent users of the emergency department:
      combining case management and drop-in group medical appointments.
AB  - BACKGROUND: Patients with complex behavioral health and medical problems can have
      a disproportionate impact on emergency departments. METHODS: We identified a
      cohort of 255 low-income, uninsured patients who had used inpatient or emergency
      department services more than 6 times in the previous 12 months. Between July
      2010 and June 2011 we enrolled 36 of these high-risk patients to participate in a
      twice-weekly drop-in group medical appointment staffed by an interdisciplinary
      team of a family physician, behavioral health professional, and nurse case
      manager. The team provided 705 patient visits in a group setting (a total of 108
      group sessions) and 652 case manager phone calls. The average number of clients
      per drop-in group medical appointment was 6.5. RESULTS: Emergency department use
      dropped from a rate of 0.58 per patient per month to 0.23 (P < .001), and
      hospital charges dropped from $1167 per patient per month to $230 (P < .001).
      Employment status increased from 4 to 14 among the 36 patients enrolled. Total
      annualized cost of the program was $66,000. CONCLUSIONS: Team-based drop-in group
      medical appointments coupled with case management seem to be a cost-effective
      model to reduce emergency department visits by some patients with complex
      behavioral health and medical needs.

PMID- 22403200
TI  - Building a patient-centered medical home: obtaining the patient's voice.
AB  - PURPOSE: Many primary care practices are currently attempting to transform into
      patient-centered medical homes (PCMHs), but little is known about how patients
      view aspects of the PCMH or how they define patient-centeredness. METHODS: We
      conducted 3 focus groups with patients from urban academic internal medicine
      practices. We asked questions about patients' perceptions of what patient
      centered care should be; care quality, teams and access; diabetes self
      management; and community connections and services. We used a grounded theory
      approach to the analysis. RESULTS: The global themes that arose in our focus
      groups included the desire for timely, clear, and courteous communication; a
      practice that is structured to facilitate an ongoing relationship with a provider
      who knows the patient; and a relationship that allows the patient both to trust
      the provider's guidance and to engage more fully in his or her own care.
      CONCLUSIONS: Our patients want a provider to know them personally and to take
      time to listen to their issues. They feel that they cannot access their providers
      in a timely fashion, find our automated phone systems frustrating, and want more
      time with their provider. Although the technological and structural
      implementation of the PCMH requires considerable effort and resources, we cannot
      neglect the relationships we have with our patients. Patients should be involved
      in this process of change to ensure we address their concerns and preserve the
      primary care relationships they value.

PMID- 22403201
TI  - Cushing syndrome: maybe not so uncommon of an endocrine disease.
AB  - BACKGROUND: Cushing syndrome (CS) is the result of extended exposure to excessive
      glucocorticoids from endogenous or exogenous sources. Traditionally, the most
      common cause of endogenous CS is a pituitary adenoma (Cushing disease). Less
      common causes are adrenocortical tumors and extrapituitary adrenocorticotropin
      producing neoplasias. OBJECTIVES: This review provides updated information
      regarding the potential for increased prevalence of CS in specific patient
      populations. Here the authors provide to family physicians clinical guidance for
      recognition of CS by presenting a case, discussing the advantages/disadvantages
      of the diagnostic tests, and discussing information about the treatment options.
      RESULTS: CS is expected to have an incidence of 10 to 15 people per million;
      however, studies of patients with diabetes, obesity, hypertension, and
      osteoporosis found a high prevalence of CS among these populations. The clinical
      manifestations of CS range from the distinctive clinical features (purple striae,
      facial plethora, proximal myopathy) to common conditions such as hypertension,
      obesity, and diabetes. Clinical practice guidelines recommend biochemical tests
      to screen patients for CS; however, the sensitivity and specificity of these
      tests vary, so a careful analysis must be performed to avoid misdiagnosis.
      CONCLUSION: CS is challenging to diagnose. Nevertheless, with a systematic
      approach to testing patients and an increased awareness of the high-risk patient
      populations, the disease can be identified in a timely manner.

PMID- 22403202
TI  - Delegating responsibility from clinicians to nonprofessional personnel: the
      example of hypertension control.
AB  - BACKGROUND: Involving nonclinician personnel in the treatment of hypertension may
      provide a solution to improve blood pressure control; however, this team-based
      approach cannot be implemented without first determining clinicians' willingness
      to delegate patient care to nonclinician team members. This study explores
      clinicians' perspectives on working with nonclinicians trained as "health
      coaches" to address medication adherence and lack of medication intensification
      among low-income patients with uncontrolled hypertension. METHODS: We used a
      qualitative research approach to determine clinicians' opinions on the Treat-to
      Target study, an intervention to improve blood pressure control. We conducted
      focus groups with clinicians who practice family medicine in a safety net clinic.
      Transcripts were analyzed using thematic content analysis. RESULTS: Seven
      overarching themes emerged: (1) Clinicians support the delegation of functions to
      health coaches; (2) clinicians like the high frequency of coach-patient
      interactions; (3) clinicians feel that health coaching assists medication
      adherence; (4) clinicians have varying views on home titration; (5) coach
      clinician communication is necessary for successful delegation; (6) coaching
      helps clinicians understand their patients' barriers to hypertension control; and
      (7) clinicians would like health coaching to continue on a permanent basis.
      CONCLUSION: Clinicians appreciate the presence of nonclinicians on the primary
      care team. In the coming era of primary care clinician shortage, clinicians can
      be supportive of nonprofessional team members assisting with the care of patients
      with hypertension.

PMID- 22403203
TI  - Correlation of the Care by Design primary care practice redesign model and the
      principles of the patient-centered medical home.
AB  - BACKGROUND: Health care reform requires major changes in the organization and
      delivery of primary care. In 2003, the University of Utah Community Clinics began
      developing Care by Design (CBD), a primary care model emphasizing access, care
      teams, and planned care. In 2007, leading primary care organizations published
      joint principles of the patient-centered medical home (PCMH), the basis for
      recognition of practices as PCMHs by the National Committee for Quality Assurance
      (NCQA). The objective of this study was to compare CBD and PCMH metrics
      conceptually and statistically. METHODS: This was an observational study in 10
      urban and rural primary care clinics including 56 providers. A self-evaluation
      included the CBD Extent of Use survey and self-estimated PCMH values. The main
      and secondary outcome measures were CBD scores and PCMH values, respectively.
      RESULTS: CBD and PCMH principles share common themes such as appropriate access,
      team-based care, the use of an augmented electronic medical record, planned care,
      and self-management support. CBD focuses more on the process of practice
      transformation. The NCQA PCMH standards focus more on structure, including
      policy, capacity, and populated electronic medical record fields. The Community
      Clinics' clinic-level PCMH/CBD correlations were low (P > .05.) CONCLUSIONS:
      Practice redesign requires an ability to assess uptake of the redesign as a
      transformation progresses. The correlation of CBD and PCMH is substantial
      conceptually but low statistically. PCMH and CBD focus on complementary aspects
      of redesign: PCMH on structure and CBD on process. Both domains should be
      addressed in practice reform. Both metrics are works in progress.

PMID- 22403204
TI  - Implementing teams in a patient-centered medical home residency practice: lessons
      learned.
AB  - INTRODUCTION: The "new model of care" calls for a new approach for primary care
      delivery that focuses on patient centeredness, quality, safety, effective and
      efficient care, and interdisciplinary teamwork. Medical education needs to
      parallel this health care reorganization. Implementing a team approach in a
      residency practice, especially in ambulatory settings, poses unique challenges.
      METHODS: We introduced interdisciplinary teams in a family medicine residency
      site, integrating clinical and educational objectives. RESULTS: We report our
      challenges and successes in the transformational journey to a patient-centered
      medical home, for which a team approach is critical to achieving high quality
      care. CONCLUSION: Establishing high-functioning interdisciplinary teams takes
      leadership commitment; the engagement of everyone in the practice; investment in
      staff, resident, and faculty development; and clear communication of vision and
      goals. Integration of clinical and educational objectives can be powerfully
      synergistic. Clinical, organizational, and educational outcomes are needed to
      evaluate impact.

PMID- 22403205
TI  - Navigating change: how outreach facilitators can help clinicians improve patient
      outcomes.
AB  - OBJECTIVE: The objective of this study was to describe outreach facilitation as
      an effective method of assisting and supporting primary care practices to improve
      processes and delivery of care. METHODS: We spent 4 years working with 83
      practices in Eastern Ontario, Canada, on the Improved Delivery of Cardiovascular
      Care through the Outreach Facilitation program. RESULTS: Primary care practices,
      even if highly motivated, face multiple challenges when providing quality patient
      care. Outreach facilitation can be an effective method of assisting and
      supporting practices to make the changes necessary to improve processes and
      delivery of care. Multiple jurisdictions use outreach facilitation for system
      redesign, improved efficiencies, and advanced access. CONCLUSIONS: The
      development and implementation of quality improvement programs using practice
      facilitation can be challenging. Our research team has learned valuable lessons
      in developing tools, finding resources, and assisting practices to reach their
      quality improvement goals. These lessons can lead to improved experiences for the
      practices and overall improved outcomes for the patients they serve.

PMID- 22403206
TI  - Managing patient populations in primary care: points of leverage.
AB  - Common "quality" metrics may represent the quality of care for large populations;
      however, they do not adequately represent quality in individual primary care
      settings, especially as stand-alone indices. Using discreet threshold values to
      measure quality in primary care may result in physicians focusing on managing
      patients by the numbers at the expense of making individualized and nuanced
      clinical decisions. Current performance measures may be misapplied as proxies for
      both cost savings and quality. We posit that developing and focusing measurement
      on high-leverage activities will yield better clinical outcomes and potentially
      lower cost. As a starting point for further work in this area, we suggest the
      development of metrics that track identification and management of depression;
      management of transitions of care; care coordination; team-based care;
      identification and support of socially frail/isolated individuals; pharmacologic
      management, including optimizing medication and dealing with adherence issues;
      and establishment of a therapeutic environment. These processes, or others like
      them, will require infrastructure that may be costly and time-consuming, and
      measuring these processes will require thought and effort. Nevertheless, we
      believe developing metrics based on high-leverage activities will yield greater
      clinical and economic returns than relying on the metrics currently in place.

PMID- 22403207
TI  - Multidisciplinary team approach to improved chronic care management for diabetic
      patients in an urban safety net ambulatory care clinic.
AB  - Since the care of patients with multiple chronic diseases such as diabetes and
      depression accounts for the majority of health care costs, effective team
      approaches to managing such complex care in primary care are needed, particularly
      since psychosocial and physical disorders coexist. Uncontrolled diabetes is a
      leading health risk for morbidity, disability and premature mortality with
      between 18-31% of patients also having undiagnosed or undertreated depression.
      Here we describe a team driven approach that initially focused on patients with
      poorly controlled diabetes (A1c > 9) that took place at a family medicare office.
      The team included: resident and faculty physicians, a pharmacist, social worker,
      nurses, behavioral medicine interns, office scheduler, and an information
      technologist. The team developed immediate integrative care for diabetic patients
      during routine office visits.

PMID- 22403208
TI  - A team-based approach to providing asthma action plans.
AB  - BACKGROUND: National guidelines for treatment of asthma include recommendations
      for providing written asthma action plans (AAPs) to improve outcomes through
      patient self-management. However, AAP completion rates remain limited in
      practice. METHODS: We developed a team-based approach for the delivery of care to
      asthma patients in a primary care setting that involved integration of an
      electronic clinical quality management system and provision of written AAPs by
      registered nurses. RESULTS: The percentage of patients with AAPs increased after
      implementation of clinical reminders and nurse-led provision of written AAPs.
      CONCLUSION: Proper training, use of an electronic clinical reminder system, and
      enhanced engagement of registered nurses can improve AAP completion rates in a
      team-based primary care setting.

PMID- 22403209
TI  - The cost of integrating a physical activity counselor in the primary health care
      team.
AB  - OBJECTIVE: This article assesses direct costs of integrating a physical activity
      counselor (PAC) into primary health care teams to improve physical activity
      levels of inactive patients. METHODS: A monthly cost analysis was conducted using
      data from 120 inactive patients, aged 18 to 69 years, who were recruited from a
      community-based family medicine practice. Relevant cost items for the intensive
      counseling group included (1) office expenses; (2) equipment purchases; (3)
      operating costs; (4) costs of training the PAC; and (5) labor costs. Physical and
      human capital were amortized over a 5-year horizon at a discount rate of 5%.
      RESULTS: Integrating a PAC into the primary health care team incurred an
      estimated one-time cost of CA$91.43 per participant per month. Results were very
      sensitive to the number of patients counseled. CONCLUSIONS: The costs associated
      with the intervention are lower than many other intervention studies attempting
      to improve population physical activity levels. Demonstrating this competitive
      cost base should encourage additional research to assess the effectiveness of
      integrating a PAC into primary health care teams to promote active living among
      patients who do not meet recommended physical activity levels.

PMID- 22403210
TI  - Shared care model in a federally qualified health care center for the homeless.
AB  - Shared Care Model at The Daily Planet, is a nonprofit, 501(c)3 charitable
      organization that was started in 1969 as a case management organization and
      evolved into a comprehensive health services center for those at risk of or
      experiencing homelessness.

PMID- 22403211
TI  - Mental health care treatment initiation when mental health services are
      incorporated into primary care practice.
AB  - PURPOSE: Most primary care patients with mental health issues are identified or
      treated in primary care rather than the specialty mental health system. Primary
      care physicians report that their patients do not have access to needed mental
      health care. When referrals are made to the specialty behavioral or mental health
      care system, rates of patients who initiate treatment are low. Collaborative care
      models, with mental health clinicians as part of the primary care medical staff,
      have been suggested as an alternative. The aim of this study is to examine rates
      of treatment startup in 2 collaborative care settings: a rural family medicine
      office and a suburban internal medicine office. In both practices referrals for
      mental health services are made within the practice. METHODS: Referral data were
      drawn from 2 convenience samples of patients referred by primary care physicians
      for collaborative mental health treatment at Fletcher Allen Health Care in
      Vermont. The first sample consisted of 93 consecutively scheduled referrals in a
      family medicine office (sample A) between January 2006 and December 2007. The
      second sample consisted of 215 consecutive scheduled referrals at an internal
      medicine office (sample B) between January 2009 and December 2009. Referral data
      identified age, sex, and presenting mental health/medical problem. RESULTS: In
      sample A, 95.5% of those patients scheduling appointments began behavioral health
      treatment; in sample B this percentage was 82%. In sample B, 69% of all patients
      initially referred for mental health care both scheduled and initiated treatment.
      CONCLUSIONS: When referred to a mental health clinician who provides on-site
      access as part of a primary care mental health collaborative care model, a high
      percentage of patients referred scheduled care. Furthermore, of those who
      scheduled care, a high percentage of patients attend the scheduled appointment.
      Findings persist despite differences in practice type, populations, locations,
      and time frames of data collection. That the findings persist across the
      different offices suggests that this model of care may contain elements that
      improve the longstanding problem of poor treatment initiation rates when primary
      care physicians refer patients for outpatient behavioral health services.

PMID- 22403212
TI  - Cardiovascular string theory.

PMID- 22403213
TI  - Killing 2 proteinases with 1 (dual-acting) stone.

PMID- 22403214
TI  - Related or unrelated donor.

PMID- 22403215
TI  - c-Myc, Captain Spaulding, and the boat to Heaven.

PMID- 22403223
TI  - A literature review and survey of childhood pneumonia etiology studies: 2000
      2010.
AB  - The Pneumonia Etiology Research for Child Health (PERCH) project is the largest
      multicountry etiology study of childhood pneumonia since the Board on Science and
      Technology in International Development studies of the 1980s. However, it is not
      the only recent or ongoing pneumonia etiology study, and even with seven sites,
      it cannot capture all epidemiologic settings in the developing world. Funding
      providers, researchers and policymakers rely on the best available evidence to
      strategically plan programs, new research directions and interventions. We aimed
      to describe the current landscape of recent pneumonia etiology studies in
      children under 5 years of age in the developed and developing world, as
      ascertained by a literature review of relevant studies with data since the year
      2000 and a survey of researchers in the field of childhood pneumonia. We
      collected information on the study population, study design, case definitions,
      laboratory samples and methods and identified pathogens. A literature review
      identified 88 studies with child pneumonia etiology results. As of June 2010, our
      survey of researchers identified an additional 65 ongoing and recently completed
      child pneumonia etiology studies. This demonstrates the broad existing context
      into which the PERCH study must be placed. However, the landscape analysis also
      reveals a multiplicity of case definitions, levels of clinician involvement,
      facility types, specimen collection, and laboratory techniques. It reinforces the
      need for the standardization of methods and analyses for present and future
      pneumonia etiology studies in order to optimize their cumulative potential to
      accurately describe the microbial causes of childhood pneumonia.

PMID- 22403224
TI  - The definition of pneumonia, the assessment of severity, and clinical
      standardization in the Pneumonia Etiology Research for Child Health study.
AB  - To develop a case definition for the Pneumonia Etiology Research for Child Health
      (PERCH) project, we sought a widely acceptable classification that was linked to
      existing pneumonia research and focused on very severe cases. We began with the
      World Health Organization's classification of severe/very severe pneumonia and
      refined it through literature reviews and a 2-stage process of expert
      consultation. PERCH will study hospitalized children, aged 1-59 months, with
      pneumonia who present with cough or difficulty breathing and have either severe
      pneumonia (lower chest wall indrawing) or very severe pneumonia (central
      cyanosis, difficulty breastfeeding/drinking, vomiting everything, convulsions,
      lethargy, unconsciousness, or head nodding). It will exclude patients with recent
      hospitalization and children with wheeze whose indrawing resolves after
      bronchodilator therapy. The PERCH investigators agreed upon standard
      interpretations of the symptoms and signs. These will be maintained by a clinical
      standardization monitor who conducts repeated instruction at each site and by
      recurrent local training and testing.

PMID- 22403225
TI  - Identification and selection of cases and controls in the Pneumonia Etiology
      Research for Child Health project.
AB  - Methods for the identification and selection of patients (cases) with severe or
      very severe pneumonia and controls for the Pneumonia Etiology Research for Child
      Health (PERCH) project were needed. Issues considered include eligibility
      criteria and sampling strategies, whether to enroll hospital or community
      controls, whether to exclude controls with upper respiratory tract infection
      (URTI) or nonsevere pneumonia, and matching criteria, among others. PERCH
      ultimately decided to enroll community controls and an additional human
      immunodeficiency virus (HIV)-infected control group at high HIV-prevalence sites
      matched on age and enrollment date of cases; controls with symptoms of URTI or
      nonsevere pneumonia will not be excluded. Systematic sampling of cases (when
      necessary) and random sampling of controls will be implemented. For each issue,
      we present the options that were considered, the advantages and disadvantages of
      each, the rationale for the methods selected for PERCH, and remaining
      implications and limitations.

PMID- 22403226
TI  - Evaluation of risk factors for severe pneumonia in children: the Pneumonia
      Etiology Research for Child Health study.
AB  - As a case-control study of etiology, the Pneumonia Etiology Research for Child
      Health (PERCH) project also provides an opportunity to assess the risk factors
      for severe pneumonia in hospitalized children at 7 sites. We identified relevant
      risk factors by literature review and iterative expert consultation. Decisions
      for inclusion in PERCH were based on comparability to published data, analytic
      plans, data collection costs and logistic feasibility, including interviewer time
      and subject fatigue. We aimed to standardize questions at all sites, but
      significant variation in the economic, cultural, and geographic characteristics
      of sites made it difficult to obtain this objective. Despite these challenges,
      the depth of the evaluation of multiple risk factors across the breadth of the
      PERCH sites should furnish new and valuable information about the major risk
      factors for childhood severe and very severe pneumonia, including risk factors
      for pneumonia caused by specific etiologies, in developing countries.

PMID- 22403227
TI  - Specimen collection for the diagnosis of pediatric pneumonia.
AB  - Diagnosing the etiologic agent of pneumonia has an essential role in ensuring the
      most appropriate and effective therapy for individual patients and is critical to
      guiding the development of treatment and prevention strategies. However,
      establishing the etiology of pneumonia remains challenging because of the
      relative inaccessibility of the infected tissue and the difficulty in obtaining
      samples without contamination by upper respiratory tract secretions. Here, we
      review the published and unpublished literature on various specimens available
      for the diagnosis of pediatric pneumonia. We discuss the advantages and
      limitations of each specimen, and discuss the rationale for the specimens to be
      collected for the Pneumonia Etiology Research for Child Health study.

PMID- 22403228
TI  - Procedures for collection of induced sputum specimens from children.
AB  - In most settings, sputum is not routinely collected for microbiological diagnosis
      from children with lower respiratory disease. To evaluate whether it is feasible
      and diagnostically useful to collect sputum in the Pneumonia Etiology Research
      for Child Health (PERCH) study, we reviewed the literature on induced sputum
      procedures. Protocols for induced sputum in children were collated from published
      reports and experts on respiratory disease and reviewed by an external advisory
      group for recommendation in the PERCH study. The advisory group compared 6
      protocols: 4 followed a nebulization technique using hypertonic saline, and 2
      followed a chest or abdomen massage technique. Grading systems for specimen
      quality were evaluated. Collecting sputum from children with lower respiratory
      tract illness is feasible and is performed around the world. An external advisory
      group recommended that sputum be collected from children hospitalized with severe
      and very severe pneumonia who participate in the PERCH study provided no
      contraindications exist. PERCH selected the nebulization technique using
      hypertonic saline.

PMID- 22403229
TI  - Laboratory methods for determining pneumonia etiology in children.
AB  - Laboratory diagnostics are a core component of any pneumonia etiology study.
      Recent advances in diagnostic technology have introduced newer methods that have
      greatly improved the ability to identify respiratory pathogens. However,
      determining the microbial etiology of pneumonia remains a challenge, especially
      in children. This is largely because of the inconsistent use of assays between
      studies, difficulties in specimen collection, and problems in interpreting the
      presence of pathogens as being causally related to the pneumonia event. The
      laboratory testing strategy for the Pneumonia Etiology Research for Child Health
      (PERCH) study aims to incorporate a broad range of diagnostic testing that will
      be standardized across the 7 participating sites. We describe the current status
      of laboratory diagnostics for pneumonia and the PERCH approach for specimen
      testing. Pneumonia diagnostics are evolving, and it is also a priority of PERCH
      to collect and archive specimens for future testing by promising diagnostic
      methods that are currently under development.

PMID- 22403231
TI  - Disk diffusion bioassays for the detection of antibiotic activity in body fluids:
      applications for the Pneumonia Etiology Research for Child Health project.
AB  - To draw inferences about the putative etiologic agents of severe pneumonia, the
      Pneumonia Etiology Research for Child Health (PERCH) project must be able to
      objectively assess antibiotic pretreatment in enrolled participants. This review
      is focused on the disk diffusion bioassay, a simple laboratory method to assess
      recent antibiotic treatment. In this method, a sensitive indicator organism is
      used to detect antimicrobial activity in body fluid specimens that have been
      inoculated on a filter paper disk and placed on agar growth medium. We reviewed
      and present several variations on the disk diffusion method as applied to serum
      or urine, including specimen handling, choice of indicator organism and medium,
      and incubation steps. Although there are limitations to the disk diffusion
      method, its low cost, ease of use, and ability to broadly detect antibiotic
      pretreatment make it an appealing method for epidemiologic studies such as PERCH.

PMID- 22403230
TI  - Use and evaluation of molecular diagnostics for pneumonia etiology studies.
AB  - Comprehensive microbiological testing will be a core function of the Pneumonia
      Etiology Research for Child Health (PERCH) project. The development stage of
      PERCH provided the time and resources necessary for us to conduct a comprehensive
      review of the current state of respiratory diagnostics. These efforts allowed us
      to articulate the unique requirements of PERCH, establish that molecular methods
      would be central to our testing strategy, and focus on a short list of candidate
      platforms. This process also highlighted critical challenges in the general
      design and interpretation of diagnostic evaluation studies, particularly in the
      field of respiratory infections. Although our final molecular diagnostic platform
      was ultimately selected on the basis of operational and strategic considerations
      determined by the specific context of PERCH, our review highlighted several
      conceptual and practical challenges in respiratory diagnostics that have broader
      relevance for the performance and interpretation of pneumonia research studies.

PMID- 22403232
TI  - The role of postmortem studies in pneumonia etiology research.
AB  - The diagnosis of etiology in severe pneumonia remains a challenging area.
      Postmortem lung tissue potentially increases the sensitivity of investigations
      for identification of causative pathogens in fatal cases of pneumonia and can
      confirm antemortem microbiological diagnoses. Tissue sampling allows assessment
      of histological patterns of disease and ancillary immunohistochemical or
      molecular diagnostic techniques. It may also enhance the recognition of
      noninfectious conditions that clinically simulate acute pneumonia. Biobanking of
      lung tissue or postmortem culture isolates offers opportunities for new pathogen
      discovery and research into host-pathogen interactions. The Pneumonia Etiology
      Research for Child Health study proposes a percutaneous needle biopsy approach to
      obtain postmortem samples, rather than a full open autopsy. This has the
      advantage of greater acceptability to relatives, but risks greater sampling
      error. Both approaches may be susceptible to microbiological contamination or
      pathogen degradation. However, previous autopsy studies have confirmed the value
      of histological examination in revealing unsuspected pathogens and influencing
      clinical guidelines for the diagnosis and treatment of future pneumonia cases.

PMID- 22403233
TI  - Bioethical considerations in developing a biorepository for the Pneumonia
      Etiology Research for Child Health project.
AB  - The Pneumonia Etiology Research for Child Health (PERCH) project has the
      potential to provide a highly valuable resource of biospecimens that may be used
      to inform future studies on the causes of pneumonia. Designing a biorepository
      for this complex project was done in collaboration with a wide range of experts
      including bioethicists. In this paper, we describe the most significant ethical
      issues encountered related to the biorepository, focusing on its structure and
      informed consent. We also outline the proposed approach to the PERCH
      biorepository, which was designed to be sensitive to the ethical, practical, and
      cultural challenges inherent to the study. Through this process, we concluded
      that biorepository governance plans and strategies for managing informed consent
      should be implemented in a way to allow for careful study in order to better
      understand the attitudes of and impact on the stakeholders involved in the study.

PMID- 22403234
TI  - Lower respiratory infections among hospitalized children in New Caledonia: a
      pilot study for the Pneumonia Etiology Research for Child Health project.
AB  - We conducted a prospective pilot study over a 1-year period in New Caledonia in
      preparation for the Pneumonia Research for Child Health (PERCH) project. The
      pathogens associated with hospitalized lower respiratory infections in children
      were identified through the use of culture of induced sputum and blood, urinary
      antigen detection, polymerase chain reaction (PCR) on respiratory specimens, and
      serology on paired sera. Respiratory viruses were detected on respiratory
      specimens by immunofluorescence and PCR, and by serology on paired sera.
      Pathogens were detected in 87.9% of the 108 hospitalized cases. Viruses
      represented 81.6% of the 152 pathogens detected. Respiratory syncytial virus and
      rhinovirus were the most frequent, accounting for 32.2% and 24.3% of the
      pathogens identified, respectively. Only 26.3% of 99 induced sputum specimens
      collected were determined to be of good quality, which may be a consequence of
      the collection method used.

PMID- 22403236
TI  - Pneumonia etiology research for child health. Introduction.

PMID- 22403235
TI  - A preliminary study of pneumonia etiology among hospitalized children in Kenya.
AB  - BACKGROUND: Pneumonia is the leading cause of childhood death in the developing
      world. Higher-quality etiological data are required to reduce this mortality
      burden. METHODS: We conducted a case-control study of pneumonia etiology among
      children aged 1-59 months in rural Kenya. Case patients were hospitalized with
      World Health Organization-defined severe pneumonia (SP) or very severe pneumonia
      (VSP); controls were outpatient children without pneumonia. We collected blood
      for culture, induced sputum for culture and multiplex polymerase chain reaction
      (PCR), and obtained oropharyngeal swab specimens for multiplex PCR from case
      patients, and serum for serology and nasopharyngeal swab specimens for multiplex
      PCR from case patients and controls. RESULTS: Of 984 eligible case patients, 810
      (84%) were enrolled in the study; 232 (29%) had VSP. Blood cultures were positive
      in 52 of 749 case patients (7%). A predominant potential pathogen was identified
      in sputum culture in 70 of 417 case patients (17%). A respiratory virus was
      detected by PCR from nasopharyngeal swab specimens in 486 of 805 case patients
      (60%) and 172 of 369 controls (47%). Only respiratory syncytial virus (RSV)
      showed a statistically significant association between virus detection in the
      nasopharynx and pneumonia hospitalization (odds ratio, 12.5; 95% confidence
      interval, 3.1-51.5). Among 257 case patients in whom all specimens (excluding
      serum specimens) were collected, bacteria were identified in 24 (9%), viruses in
      137 (53%), mixed viral and bacterial infection in 39 (15%), and no pathogen in 57
      (22%); bacterial causes outnumbered viral causes when the results of the case
      control analysis were considered. CONCLUSIONS: A potential etiology was detected
      in >75% of children admitted with SP or VSP. Except for RSV, the case-control
      analysis did not detect an association between viral detection in the nasopharynx
      and hospitalization for pneumonia.

PMID- 22403237
TI  - Childhood pneumonia as a global health priority and the strategic interest of the
      Bill & Melinda Gates Foundation.
AB  - Pneumonia kills more children than any other disease--more than HIV/AIDS,
      malaria, and measles combined. Introduction of vaccines against pneumococcus and
      Haemophilus influenzae type b (the most important causes of severe pneumonia in
      young children), increasing resistance to antibiotics, and changes in HIV
      prevalence will likely change patterns of pneumonia etiology in developing
      countries. Studies such as Pneumonia Etiology Research for Child Health (PERCH)
      that take advantage of new diagnostic technologies are needed to provide an
      updated and more precise description of the microbial causes of pneumonia and to
      inform decisions around treatment algorithms and vaccine development and
      introduction. In recognition of its importance for global health and especially
      its significance as an ongoing cause of gross inequity in risks, The Bill &
      Melinda Gates Foundation has made pneumonia an important part of its global
      health strategy and PERCH a centerpiece of its Pneumonia Program.

PMID- 22403238
TI  - The Pneumonia Etiology Research for Child Health Project: a 21st century
      childhood pneumonia etiology study.
AB  - The Pneumonia Etiology Research for Child Health (PERCH) project is a 7-country,
      standardized, comprehensive evaluation of the etiologic agents causing severe
      pneumonia in children from developing countries. During previous etiology
      studies, between one-quarter and one-third of patients failed to yield an obvious
      etiology; PERCH will employ and evaluate previously unavailable innovative, more
      sensitive diagnostic techniques. Innovative and rigorous epidemiologic and
      analytic methods will be used to establish the causal association between
      presence of potential pathogens and pneumonia. By strategic selection of study
      sites that are broadly representative of regions with the greatest burden of
      childhood pneumonia, PERCH aims to provide data that reflect the epidemiologic
      situation in developing countries in 2015, using pneumococcal and Haemophilus
      influenzae type b vaccines. PERCH will also address differences in host,
      environmental, and/or geographic factors that might determine pneumonia etiology
      and, by preserving specimens, will generate a resource for future research and
      pathogen discovery.

PMID- 22403239
TI  - Improving the accuracy of demographic and molecular clock model comparison while
      accommodating phylogenetic uncertainty.
AB  - Recent developments in marginal likelihood estimation for model selection in the
      field of Bayesian phylogenetics and molecular evolution have emphasized the poor
      performance of the harmonic mean estimator (HME). Although these studies have
      shown the merits of new approaches applied to standard normally distributed
      examples and small real-world data sets, not much is currently known concerning
      the performance and computational issues of these methods when fitting complex
      evolutionary and population genetic models to empirical real-world data sets.
      Further, these approaches have not yet seen widespread application in the field
      due to the lack of implementations of these computationally demanding techniques
      in commonly used phylogenetic packages. We here investigate the performance of
      some of these new marginal likelihood estimators, specifically, path sampling
      (PS) and stepping-stone (SS) sampling for comparing models of demographic change
      and relaxed molecular clocks, using synthetic data and real-world examples for
      which unexpected inferences were made using the HME. Given the drastically
      increased computational demands of PS and SS sampling, we also investigate a
      posterior simulation-based analogue of Akaike's information criterion (AIC)
      through Markov chain Monte Carlo (MCMC), a model comparison approach that shares
      with the HME the appealing feature of having a low computational overhead over
      the original MCMC analysis. We confirm that the HME systematically overestimates
      the marginal likelihood and fails to yield reliable model classification and show
      that the AICM performs better and may be a useful initial evaluation of model
      choice but that it is also, to a lesser degree, unreliable. We show that PS and
      SS sampling substantially outperform these estimators and adjust the conclusions
      made concerning previous analyses for the three real-world data sets that we
      reanalyzed. The methods used in this article are now available in BEAST, a
      powerful user-friendly software package to perform Bayesian evolutionary
      analyses.

PMID- 22403240
TI  - Associations between incident ischemic stroke events and stroke and
      cardiovascular disease-related genome-wide association studies single nucleotide
      polymorphisms in the Population Architecture Using Genomics and Epidemiology
      study.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified loci
      associated with ischemic stroke (IS) and cardiovascular disease (CVD) in European
      descent individuals, but their replication in different populations has been
      largely unexplored. METHODS AND RESULTS: Nine single nucleotide polymorphisms
      (SNPs) selected from GWAS and meta-analyses of stroke, and 86 SNPs previously
      associated with myocardial infarction and CVD risk factors, including blood
      lipids (high density lipoprotein [HDL], low density lipoprotein [LDL], and
      triglycerides), type 2 diabetes, and body mass index (BMI), were investigated for
      associations with incident IS in European Americans (EA) N=26 276, African
      Americans (AA) N=8970, and American Indians (AI) N=3570 from the Population
      Architecture using Genomics and Epidemiology Study. Ancestry-specific fixed
      effects meta-analysis with inverse variance weighting was used to combine study
      specific log hazard ratios from Cox proportional hazards models. Two of 9 stroke
      SNPs (rs783396 and rs1804689) were significantly associated with [corrected] IS
      hazard in AA; none were significant in this large EA cohort. Of 73 CVD risk
      factor SNPs tested in EA, 2 (HDL and triglycerides SNPs) were associated with IS.
      In AA, SNPs associated with LDL, HDL, and BMI were significantly associated with
      IS (3 of 86 SNPs tested). Out of 58 SNPs tested in AI, 1 LDL SNP was
      significantly associated with IS. CONCLUSIONS: Our analyses showing lack of
      replication in spite of reasonable power for many stroke SNPs and differing
      results by ancestry highlight the need to follow up on GWAS findings and conduct
      genetic association studies in diverse populations. We found modest IS
      associations with BMI and lipids SNPs, though these findings require
      confirmation.

PMID- 22403242
TI  - Distinguishing hyperglycemic changes by Set7 in vascular endothelial cells.
AB  - RATIONALE: Epigenetic changes are implicated in the persisting vascular effects
      of hyperglycemia. The precise mechanism whereby chromatin structure and
      subsequent gene expression are regulated by glucose in vascular endothelial cells
      remain to be fully defined. OBJECTIVE: We have studied the molecular and
      functional mechanism whereby the Set7 methyltransferase associates with chromatin
      formation and histone methylation in vascular cells in response to current and
      previous exposure to glucose. METHODS AND RESULTS: To characterize the molecular
      and functional identity of the Set7 protein, we used vascular cells
      overexpressing or lacking Set7. Chromatin fractionation for mono-methylation of
      lysine 4 on histone H3 identified methyltransferase activity. Immunofluorescence
      experiments strongly suggest that Set7 protein accumulates in the nucleus in
      response to hyperglycemia. Moreover, activation of proinflammatory genes by high
      glucose is dependent on Set7 but distinguished by H3K4m1 gene patterns. We show
      that transient hyperglycemia regulates the expression of proinflammatory genes in
      vascular endothelial cells in vitro and the persistent increase in glucose
      induced gene expression in the aorta of nondiabetic mice. CONCLUSIONS: This study
      uncovers that the response to hyperglycemia in vascular endothelial cells
      involves the H3K4 methyltransferase, Set7. This enzyme appears to regulate
      glucose-induced chromatin changes and gene expression not only by H3K4m1
      dependent but also H3K4m1-independent pathways. Furthermore, Set7 appears to be
      responsible for sustained vascular gene expression in response to prior
      hyperglycemia and is a potential molecular mechanism for the phenomenon of
      hyperglycemic memory.

PMID- 22403241
TI  - Interaction between NFkappaB and NFAT coordinates cardiac hypertrophy and
      pathological remodeling.
AB  - RATIONALE: Both nuclear factors of activated T cells (NFAT) and nuclear factor
      kappaB (NFkappaB) are Rel homology domain (RHD)-containing transcription factors
      whose independent activities are critically involved in regulating cardiac
      hypertrophy and failure. OBJECTIVE: To determine the potential functional
      interaction between NFAT and NFkappaB signaling pathways in cardiomyocytes and
      its role in cardiac hypertrophy and remodeling. METHODS AND RESULTS: We
      identified a novel transcriptional regulatory mechanism whereby NFkappaB and NFAT
      directly interact and synergistically promote transcriptional activation in
      cardiomyocytes. We show that the p65 subunit of NFkappaB coimmunoprecipitates
      with NFAT in cardiomyocytes, and this interaction maps to the RHD within p65.
      Overexpression of the p65-RHD disrupts the association between endogenous p65 and
      NFATc1, leading to reduced transcriptional activity. Overexpression of IkappaB
      kinase beta (IKKbeta) or p65-RHD causes nuclear translocation of NFATc1, and
      expression of a constitutively nuclear NFATc1-SA mutant similarly facilitated p65
      nuclear translocation. Combined overexpression of p65 and NFATc1 promotes
      synergistic activation of NFAT transcriptional activity in cardiomyocytes,
      whereas inhibition of NFkappaB with IkappaBalphaM or dominant negative IKKbeta
      reduces NFAT activity. Importantly, agonist-induced NFAT activation is reduced in
      p65 null mouse embryonic fibroblasts (MEFs) compared with wild-type MEFs. In
      vivo, cardiac-specific deletion of p65 using a Cre-loxP system causes a ~50%
      reduction in NFAT activity in luciferase reporter mice. Moreover, ablation of p65
      in the mouse heart decreases the hypertrophic response after pressure overload
      stimulation, reduces the degree of pathological remodeling, and preserves
      contractile function. CONCLUSIONS: Our results suggest a direct interaction
      between NFAT and NFkappaB that effectively integrates 2 disparate signaling
      pathways in promoting cardiac hypertrophy and ventricular remodeling.

PMID- 22403243
TI  - Regulation of cardiac microRNAs by bone marrow mononuclear cell therapy in
      myocardial infarction.
AB  - BACKGROUND: Cell therapy with bone marrow-derived mononuclear cells (BMCs) can
      improve recovery of cardiac function after ischemia; however, the molecular
      mechanisms are not yet fully understood. MicroRNAs (miRNAs) are key regulators of
      gene expression and modulate the pathophysiology of cardiovascular diseases.
      METHODS AND RESULTS: We demonstrated that intramyocardial delivery of BMCs in
      infarcted mice regulates the expression of cardiac miRNAs and significantly
      downregulates the proapoptotic miR-34a. In vitro studies confirmed that the
      supernatant of BMC inhibited the expression of H(2)O(2)-induced miR-34a and
      cardiomyocytes apoptosis. These effects were blocked by neutralizing antibodies
      directed against insulin-like growth factor-1 (IGF-1). Indeed, IGF-1
      significantly inhibited H(2)O(2)-induced miR-34a expression, and miR-34a
      overexpression abolished the antiapoptotic effect of IGF-1. Likewise, inhibition
      of IGF-1 signaling in vivo abolished the BMC-mediated inhibition of miR-34
      expression and the protective effect on cardiac function and increased apoptosis
      and cardiac fibrosis. IGF-1 specifically blocked the expression of the precursor
      and the mature miR-34a, but did not interfere with the transcription of the
      primary miR-34a demonstrating that IGF-1 blocks the processing of miR-34a.
      CONCLUSIONS: Together, our data demonstrate that the paracrine regulation of
      cardiac miRNAs by transplanted BMCs contributes to the protective effects of cell
      therapy. BMCs release IGF-1, which inhibits the processing of miR-34a, thereby
      blocking cardiomyocyte apoptosis.

PMID- 22403244
TI  - Introduction from the Agency for Healthcare Research and Quality.

PMID- 22403245
TI  - Health care in the Netherlands.
AB  - This article analyzes Dutch experiences of health care reform--in particular in
      primary care--with emphasis on lessons for current United States health care
      reforms. Recent major innovations were the introduction of private insurance
      based on the principles of primary care-led health care and including all
      citizens irrespective of their financial, employment, or health status;
      introduction of primary care collaboratives for out-of-hour services and chronic
      disease management; and primary care team building, including practice nurses.
      These innovations were introduced on top of a strong primary care tradition of
      family practices with defined populations based on patient panels, practice-based
      research, evidence-based medicine, large-scale computerization, and strong
      primary care health informatics. Dutch health reform redirected payment to
      support introduction of innovative health plans and strengthening of primary care
      to respond to public health objectives. Five recommendations for US primary care
      follow from this Dutch experience: (1) a private insurance model is compatible
      with thriving primary care, but it must include all people, especially the most
      vulnerable in society, and espouse a primary care-led health care system; (2)
      patient panels or practice lists strengthen continuity of care and community
      orientation to focus on and respond to local needs; (3) reward collaboration
      within primary care and between primary care, hospital care, and public health;
      (4) stimulate primary care professionals to exert their passion and expertise
      through participation in primary care research and development; and (5) health
      informatics should be primary care based, preferably adopting the International
      Classification of Primary Care. With these recommendations, it will be possible
      for the United States to obtain better population health for its population.

PMID- 22403246
TI  - The Australian experiment: how primary health care organizations supported the
      evolution of a primary health care system.
AB  - Primary health care in Australia has undergone 2 decades of change. Starting with
      a vision for a national health strategy with general practice at its core,
      Australia established local meso-level primary health care organizations-
      Divisions of General Practice--moving from focus on individual practitioners to a
      professional collective local voice. The article identifies how these meso-level
      organizations have helped the Australian primary health care system evolve by
      supporting the roll-out of initiatives including national practice accreditation,
      a focus on quality improvement, expansion of multidisciplinary teams into general
      practice, regional integration, information technology adoption, and improved
      access to care. Nevertheless, there are still challenges to ensuring equitable
      access and the supply and distribution of a primary care workforce, addressing
      the increasing rates of chronic disease and obesity, and overcoming the
      fragmentation of funding and accountability in the Australian system.

PMID- 22403247
TI  - International learning on increasing the value and effectiveness of primary care
      (I LIVE PC).

PMID- 22403248
TI  - Innovative and diverse strategies toward primary health care reform: lessons
      learned from the Canadian experience.
AB  - INTRODUCTION: In the last decade, Canadian provincial and territorial health
      systems have taken diverse approaches to strengthening primary care delivery.
      Although the Canadian and US systems differ in significant ways, important
      commonalities include the organization of care delivery, core principles guiding
      primary care reform, and some degree of provincial/state autonomy. This suggests
      that Canadian experiences, which employed a variety of tools, strategies, and
      policies, may be informative for US efforts to improve primary care. INNOVATIONS:
      The range of primary care reform initiatives implemented across Canada target
      organizational infrastructure, provider payment, health care workforce, and
      quality and safety. Primary care teams and networks in which multiple physicians
      work in concert with other providers have become widespread in some provinces;
      they vary on a number of dimensions, including physician payment, incorporation
      of other providers, and formal enrolment of patients. Family medicine is
      attracting more recent medical school graduates, a trend likely affected by new
      physician payment models, increases in the number of primary care providers, and
      efforts to better integrate nonphysician providers into clinical practice.
      Efforts to integrate electronic medical records into practice and pursue quality
      improvement strategies are gaining ground in some provinces. CONCLUSIONS:
      Canadian primary care reform initiatives rely on voluntary participation,
      incremental change, and diverse models, encouraging engagement and collaboration
      from a range of stakeholders including patients, providers, and policymakers.
      Cross-country collaboration in evaluating and translating Canada's primary care
      reform efforts are likely to yield important lessons for the US experience.

PMID- 22403249
TI  - General practice and primary health care in Denmark.
AB  - General practice is the corner stone of Danish primary health care. General
      practitioners (GPs) are similar to family physicians in the United States. On
      average, all Danes have 6.9 contacts per year with their GP (in-person,
      telephone, or E-mail consultation). General practice is characterized by 5 key
      components: (1) a list system, with an average of close to 1600 persons on the
      list of a typical GP; (2) the GP as gatekeeper and first-line provider in the
      sense that a referral from a GP is required for most office-based specialists and
      always for in- and outpatient hospital treatment; (3) an after-hours system
      staffed by GPs on a rota basis; (4) a mixed capitation and fee-for-service
      system; and (5) GPs are self-employed, working on contract for the public funder
      based on a national agreement that details not only services and reimbursement
      but also opening hours and required postgraduate education. The contract is
      (re)negotiated every 2 years. General practice is embedded in a universal tax
      funded health care system in which GP and hospital services are free at the point
      of use. The current system has evolved over the past century and has shown an
      ability to adapt flexibly to new challenges. Practice units are fairly small:
      close to 2 GPs per unit plus nurses and secretaries. The units are fully
      computerized, that is, with computer-based patient records and submission of
      prescriptions digitally to pharmacies etc. Over the past few years a decrease in
      solo practices has been seen and is expected to accelerate, in part because of
      the GP age structure, with many GPs retiring and new GPs not wanting to practice
      alone. This latter workforce trend is pointing toward a new model with employed
      GPs, particularly in rural areas.

PMID- 22403250
TI  - International learning on increasing the value and effectiveness of primary care
      (I LIVE PC) New Zealand.
AB  - New Zealand (NZ) has a central government-driven, tax-funded health system with
      the state as dominant payer. The NZ experience precedes and endorses the US
      concept of patient-centered medical homes providing population-based, nonepisodic
      care supported by network organizations. These networks provide administration,
      budget holding, incentivized programs, data feedback, peer review, education,
      human relations, and health information technology support and resources. Key
      elements include enrolled populations; an interdisciplinary team approach; health
      information technology interoperability and access between all providers as well
      as patients; devolution of hospital-based services into the community;
      intersectorial integration; blended payments (a combination of universal
      capitated funding, patient copayments, and targeted fee-for-service for specific
      items); and a balance of clinical, corporate, and community governance. In this
      article, we discuss reforms to NZ's primary care arrangements over the past 2
      decades and reflect on the lessons learned, their relevance to the United States,
      and issues that remain to be resolved.

PMID- 22403251
TI  - Primary medical care in the United kingdom.
AB  - Since 1948 health care in the United Kingdom (UK) has been centrally funded
      through the National Health Service (NHS). The NHS provides both primary and
      specialist health care which is largely free at the point of delivery. Family
      practitioners are responsible for registered populations of patients and
      typically work in groups of 4-6 self-employed physicians. They hire nurses and a
      range of other ancillary staff, and act as gatekeepers to specialist care. Recent
      reforms include a wide range of national quality improvement initiatives and a
      pay for performance scheme that accounts for around 25% of family practitioners'
      income. These reforms have been associated with some major improvements in
      quality, including improved chronic disease management and reduced waiting times
      for specialist care. The four countries of the UK differ in some important
      aspects of health care organization: proposed reforms in England would move
      towards a more market-driven system, with family practitioners acting as payers
      for specialist care and controlling 70% of the NHS budget. The other countries
      (Scotland, Wales and Northern Ireland) focus more on trying to create area-based
      integrated systems of care.

PMID- 22403252
TI  - Digestive vacuole of Plasmodium falciparum released during erythrocyte rupture
      dually activates complement and coagulation.
AB  - Severe Plasmodium falciparum malaria evolves through the interplay among
      capillary sequestration of parasitized erythrocytes, deregulated inflammatory
      responses, and hemostasis dysfunction. After rupture, each parasitized
      erythrocyte releases not only infective merozoites, but also the digestive
      vacuole (DV), a membrane-bounded organelle containing the malaria pigment
      hemozoin. In the present study, we report that the intact organelle, but not
      isolated hemozoin, dually activates the alternative complement and the intrinsic
      clotting pathway. Procoagulant activity is destroyed by phospholipase C
      treatment, indicating a critical role of phospholipid head groups exposed at the
      DV surface. Intravenous injection of DVs caused alternative pathway complement
      consumption and provoked apathy and reduced nociceptive responses in rats.
      Ultrasonication destroyed complement-activating and procoagulant properties in
      vitro and rendered the DVs biologically inactive in vivo. Low-molecular-weight
      dextran sulfate blocked activation of both complement and coagulation and
      protected animals from the harmful effects of DV infusion. We surmise that in
      chronic malaria, complement activation by and opsonization of the DV may serve a
      useful function in directing hemozoin to phagocytic cells for safe disposal.
      However, when the waste disposal system of the host is overburdened, DVs may
      transform into a trigger of pathology and therefore represent a potential
      therapeutic target in severe malaria.

PMID- 22403253
TI  - Engagement of NKp30 on Vdelta1 T cells induces the production of CCL3, CCL4, and
      CCL5 and suppresses HIV-1 replication.
AB  - Natural cytotoxicity receptors (NCRs) were originally identified as specific
      natural killer cell activating receptors that, on binding to their endogenous
      ligands, trigger the killing of tumor cell targets. We recently described the
      differentiation of a novel subset of NCR(+) Vdelta1 T cells characterized by a
      remarkably high cytolytic potential against cancer cells. Here we demonstrate
      that the engagement of NKp30, one of the NCRs expressed de novo on Vdelta1 T
      cells after stimulation, triggers the production of high levels of CCL3/MIP
      1alpha, CCL4/ MIP-1beta, and CCL5/RANTES but not of CXCL12/SDF-1. In turn, this
      NKp30-induced secretion of cc-chemokines is able to significantly suppress the
      replication of a CCR5 tropic strain of HIV-1 in CD4(+)/CCR5(+) infected PM1 cell
      lines. This experimental evidence disclosing an unanticipated antiviral function
      of NCR(+) Vdelta1 T cells opens new avenues for understanding the pathogenic role
      and for manipulating the function of gammadelta T cells in HIV-1 infection.

PMID- 22403254
TI  - Anti-CD20 (rituximab) therapy for anti-IFN-gamma autoantibody-associated
      nontuberculous mycobacterial infection.
AB  - Patients with anti-IFN-gamma autoantibodies have impaired IFN-gamma signaling,
      leading to severe disseminated infections with intracellular pathogens,
      especially nontuberculous mycobacteria. Disease may be severe and progressive,
      despite aggressive treatment. To address the underlying pathogenic IFN-gamma
      autoantibodies we used the therapeutic monoclonal rituximab (anti-CD20) to target
      patient B cells. All subjects received between 8 and 12 doses of rituximab within
      the first year to maintain disease remission. Subsequent doses were given for
      relapsed infection. We report 4 patients with refractory disease treated with
      rituximab who had clinical and laboratory evidence of therapeutic response as
      determined by clearance of infection, resolution of inflammation, reduction of
      anti-IFN-gamma autoantibody levels, and improved IFN-gamma signaling.

PMID- 22403256
TI  - Neonatal lymph node stromal cells drive myelodendritic lineage cells into a
      distinct population of CX3CR1+CD11b+F4/80+ regulatory macrophages in mice.
AB  - Beyond providing a scaffold for immune cells, recent studies indicate that lymph
      node stromal cells provide potent regulatory capacities that affect the quality
      of adaptive immune responses. In this study, we provide evidence that neonatal
      lymph node stromal cells (nnLNSCs) consistently promote the differentiation of
      macrophage dendritic cell progenitors as well as mature and immature dendritic
      cells into a distinct population of CX3CR1(+) CD11b(+)F4/80(+) regulatory
      macrophages (regMPhi). These cells possess remarkably low levels of T cell
      costimulatory molecules as well as MHC class II molecules. regMPhi do not
      interfere with early T-cell activation but, via nitric oxide secretion,
      efficiently suppress T-cell proliferation. Furthermore, CD4(+) T cells
      proliferating in the presence of regMPhi gain immunosuppressive capacity and MPhi
      isolated from day 3 nnLNs are T-cell immunosuppressive. Adoptive transfer of
      antigen-loaded regMPhi induce a profound antigen-specific immune suppression in
      vivo. Together our data show that nnLNSCs skew the differentiation of dendritic
      cells and their progenitors toward regMPhi, thus revealing a novel mechanism for
      local immune regulation.

PMID- 22403257
TI  - Helicobacter pylori eradication therapy is effective in the treatment of early
      stage H pylori-positive gastric diffuse large B-cell lymphomas.
AB  - An explorative study evaluates the efficacy of Helicobacter pylori (HP)
      eradication (HPE) therapy on early-stage gastric diffuse large B-cell lymphomas
      (DLBCLs) without features of mucosa-associated lymphoid tissue (MALT), the pure
      (de novo) DLBCLs, in comparison with its efficacy on high-grade transformed
      gastric MALT lymphomas, the DLBCL(MALT). In total, 50 patients of stage IE/IIE1
      HP-positive gastric DLBCLs with frontline HPE treatment were included. HP
      infection was successfully eradicated in 100% (16/16) of the pure (de novo) DLBCL
      patients and 94.1% (32/34) of the DLBCL(MALT) patients. In total, 68.8% (11/16)
      of pure (de novo) DLBCL patients and 56.3% (18/32) of DLBCL(MALT) patients
      achieved complete pathologic remission (pCR) after HPE therapy. The median time
      to pCR was 2.1 months (95% confidence interval, 0.6%-3.7%) for pure (de novo)
      DLBCLs and 5.0 months (95% confidence interval, 2.8%-7.5%; P = .024) for
      DLBCL(MALT). At a median follow-up of 7.7 years, all patients with pCR after HPE
      therapy were alive and free of lymphomas, except for one patient with pure (de
      novo) DLBCL who died of lung cancer. Similar to DLBCL(MALT), a substantial
      portion of early-stage HP-positive gastric pure (de novo) DLBCLs remains HP
      dependent and responds to antibiotic treatment. Prospective studies to validate
      the findings are warranted.

PMID- 22403255
TI  - Functional STAT3 deficiency compromises the generation of human T follicular
      helper cells.
AB  - T follicular helper (Tfh) cells are critical for providing the necessary signals
      to induce differentiation of B cells into memory and Ab-secreting cells.
      Accordingly, it is important to identify the molecular requirements for Tfh cell
      development and function. We previously found that IL-12 mediates the
      differentiation of human CD4(+) T cells to the Tfh lineage, because IL-12 induces
      naive human CD4(+) T cells to acquire expression of IL-21, BCL6, ICOS, and CXCR5,
      which typify Tfh cells. We have now examined CD4(+) T cells from patients
      deficient in IL-12Rbeta1, TYK2, STAT1, and STAT3 to further explore the pathways
      involved in human Tfh cell differentiation. Although STAT1 was dispensable,
      mutations in IL12RB1, TYK2, or STAT3 compromised IL-12-induced expression of IL
      21 by human CD4(+) T cells. Defective expression of IL-21 by STAT3-deficient
      CD4(+) T cells resulted in diminished B-cell helper activity in vitro.
      Importantly, mutations in STAT3, but not IL12RB1 or TYK2, also reduced Tfh cell
      generation in vivo, evidenced by decreased circulating CD4(+)CXCR5(+) T cells.
      These results highlight the nonredundant role of STAT3 in human Tfh cell
      differentiation and suggest that defective Tfh cell development and/or function
      contributes to the humoral defects observed in STAT3-deficient patients.

PMID- 22403258
TI  - Basis of CTLA-4 function in regulatory and conventional CD4(+) T cells.
AB  - CTLA-4 proteins contribute to the suppressor function of regulatory T cells
      (Tregs), but the mechanism by which they do so remains incompletely understood.
      In the present study, we assessed CTLA-4 protein function in both Tregs and
      conventional (Tconv) CD4(+) T cells. We report that CTLA-4 proteins are
      responsible for all 3 characteristic Treg functions of suppression, TCR
      hyposignaling, and anergy. However, Treg suppression and anergy only required the
      external domain of CTLA-4, whereas TCR hyposignaling required its internal
      domain. Surprisingly, TCR hyposignaling was neither required for Treg suppression
      nor anergy because costimulatory blockade by the external domain of CTLA-4 was
      sufficient for both functions. We also report that CTLA-4 proteins were localized
      in Tregs in submembrane vesicles that rapidly recycled to/from the cell surface,
      whereas CTLA-4 proteins in naive Tconv cells were retained in Golgi vesicles away
      from the cell membrane and had no effect on Tconv cell function. However, TCR
      signaling of Tconv cells released CTLA-4 proteins from Golgi retention and caused
      activated Tconv cells to acquire suppressor function. Therefore, the results of
      this study demonstrate the importance of intracellular localization for CTLA-4
      protein function and reveal that CTLA-4 protein externalization imparts
      suppressor function to both regulatory and conventional CD4(+) T cells.

PMID- 22403260
TI  - Human NK cells at early stages of differentiation produce CXCL8 and express CD161
      molecule that functions as an activating receptor.
AB  - Human natural killer (NK) cell development is a step-by-step process
      characterized by phenotypically identified stages. CD161 is a marker informative
      of the NK cell lineage commitment, whereas CD56, CD117, and CD94/NKG2A contribute
      to define discrete differentiation stages. In cells undergoing in vitro
      differentiation from CD34(+) umbilical cord blood (UCB) progenitors, LFA-1
      expression allowed to discriminate between immature noncytolytic
      CD161(+)CD56(+)LFA-1(-) and more differentiated cytolytic CD161(+)CD56(+)LFA-1(+)
      NK cells. CD161(+)CD56(+)LFA-1(-) NK cells produce large amounts of CXCL8 after
      phorbol myristate acetate (PMA) or cytokine treatment. Remarkably, CXCL8 mRNA
      expression was also detected in fresh stage III immature NK cells isolated from
      tonsils and these cells expressed CXCL8 protein on PMA stimulation. Within in
      vitro UCB-derived CD161(+)CD56(+)LFA-1(-) NK cells, CXCL8 release was also
      induced on antibody-mediated cross-linking of NKp44 and CD161. Such unexpected
      activating function of CD161 was confined to the CD161(+)CD56(+)LFA-1(-) subset,
      because it did not induce cytokine release or CD107a expression in
      CD161(+)CD56(+)LFA-1(+) cells or in mature peripheral blood NK cells. Anti-CXCL8
      neutralizing antibody induced a partial inhibition of NK cell differentiation,
      which suggests a regulatory role of CXCL8 during early NK cell differentiation.
      Altogether, these data provide novel information that may offer clues to optimize
      NK cell maturation in hematopoietic stem cell transplantation.

PMID- 22403259
TI  - Dendritic cells and regulation of graft-versus-host disease and graft-versus
      leukemia activity.
AB  - Hematopoietic stem cell transplantation is the only curative treatment for many
      malignant hematologic diseases, with an often critical graft-versus-leukemia
      effect. Despite peritransplant prophylaxis, GVHD remains a significant cause of
      posthematopoietic stem cell transplantation morbidity and mortality. Traditional
      therapies have targeted T cells, yet immunostimulatory dendritic cells (DCs) are
      critical in the pathogenesis of GVHD. Furthermore, DCs also have tolerogenic
      properties. Monitoring of DC characteristics may be predictive of outcome, and
      therapies that target DCs are innovative and promising. DCs may be targeted in
      vivo or tolerogenic (tol) DCs may be generated in vitro and given in the
      peritransplant period. Other cellular therapies, notably regulatory T cells
      (T(reg)) and mesenchymal stem cells, mediate important effects through DCs and
      show promise for the prevention and treatment of GVHD in early human studies.
      Therapies are likely to be more effective if they have synergistic effects or
      target both DCs and T cells in vivo, such as tolDCs or T(reg). Given the
      effectiveness of tolDCs in experimental models of GVHD and their safety in early
      human studies for type 1 diabetes, it is crucial that tolDCs be investigated in
      the prevention and treatment of human GVHD while ensuring conservation of graft
      versus-leukemia effects.

PMID- 22403261
TI  - High community faecal carriage rates of CTX-M ESBL-producing Escherichia coli in
      a specific population group in Birmingham, UK.
AB  - OBJECTIVES: To determine the proportion of E. coli carrying specific CTX-M
      extended-spectrum beta-lactamase (ESBL) genotypes in a community population of
      East and North Birmingham. METHODS: General practice and outpatient stool samples
      from 732 individuals submitted for examination for faecal pathogens in 2010 were
      screened for ESBL-producing E. coli using chromogenic agar. Multiplex PCR,
      denaturing HPLC, DNA sequencing and PFGE were used to determine the CTX-M
      genotype and clonal subtype. Isolates from people were assigned to 'Europe',
      'Middle East/South Asia' (MESA) or 'uncategorized' groups using software to
      determine probable global origin based on the subject's full name. RESULTS:
      Prevalence of CTX-M carriage in the sample population was 11.3%. There was a
      statistically significant difference (P < 0.001) between carriage in the Europe
      group (8.1%) and the MESA group (22.8%). There was also a higher rate of carriage
      of CTX-M-15-producing E. coli (P < 0.001) in MESA subjects. CONCLUSIONS: The high
      community carriage rate and the significant difference in carriage between the
      Europe and MESA subjects may have important consequences for therapy. If the
      rising trend in carriage of bacteria producing ESBLs continues, guidelines for
      empirical therapy for patients presenting from the community may need to be
      modified. The findings also raise the concern that the pattern and routes of
      spread of CTX-M-15 may be replicated in the future by broader-spectrum beta
      lactamases, such as New Delhi metallo-beta-lactamase ('NDM-1').

PMID- 22403262
TI  - Daily 300 mg dose of linezolid for multidrug-resistant and extensively drug
      resistant tuberculosis: updated analysis of 51 patients.
AB  - OBJECTIVES: Linezolid may be an effective treatment for multidrug-resistant (MDR)
      and extensively drug-resistant (XDR) tuberculosis (TB). The objective was to
      evaluate the efficacy, tolerability and adverse events of a 300 mg daily dose of
      linezolid in the treatment of MDR/XDR-TB. PATIENTS AND METHODS: We
      retrospectively reviewed the medical records of 51 MDR-TB patients, including 26
      patients (51%) with XDR-TB, to evaluate the safety, tolerability and efficacy of
      therapy with 300 mg/day linezolid. All patients had failed previous treatments
      with second-line anti-TB drugs. RESULTS: Patients were treated with linezolid for
      a median of 413 days (IQR 237-622 days). Favourable treatment outcome (treatment
      success or still on treatment after culture conversion) was achieved in 40
      patients (78%) with culture conversion at a median of 55 days (IQR 41-91 days)
      from the start of linezolid therapy. Eleven patients (22%) had unfavourable
      outcomes (treatment failure or death) and 14 (27%) discontinued treatment due to
      neurotoxicity (peripheral or optic neuropathy) after a median of 278 days (IQR
      174-412 days). CONCLUSIONS: Our findings suggest that linezolid at a daily dose
      of 300 mg is effective against intractable MDR/XDR-TB, and may be associated with
      fewer neuropathic side effects than a daily dose of 600 or 1200 mg.

PMID- 22403263
TI  - Mobile phone use and glioma risk: comparison of epidemiological study results
      with incidence trends in the United States.
AB  - OBJECTIVE: In view of mobile phone exposure being classified as a possible human
      carcinogen by the International Agency for Research on Cancer (IARC), we
      determined the compatibility of two recent reports of glioma risk (forming the
      basis of the IARC's classification) with observed incidence trends in the United
      States. DESIGN: Comparison of observed rates with projected rates of glioma
      incidence for 1997-2008. We estimated projected rates by combining relative risks
      reported in the 2010 Interphone study and a 2011 Swedish study by Hardell and
      colleagues with rates adjusted for age, registry, and sex; data for mobile phone
      use; and various latency periods. SETTING: US population based data for glioma
      incidence in 1992-2008, from 12 registries in the Surveillance, Epidemiology, and
      End Results (SEER) programme (Atlanta, Detroit, Los Angeles, San Francisco, San
      Jose-Monterey, Seattle, rural Georgia, Connecticut, Hawaii, Iowa, New Mexico, and
      Utah). PARTICIPANTS: Data for 24,813 non-Hispanic white people diagnosed with
      glioma at age 18 years or older. RESULTS: Age specific incidence rates of glioma
      remained generally constant in 1992-2008 (-0.02% change per year, 95% confidence
      interval -0.28% to 0.25%), a period coinciding with a substantial increase in
      mobile phone use from close to 0% to almost 100% of the US population. If phone
      use was associated with glioma risk, we expected glioma incidence rates to be
      higher than those observed, even with a latency period of 10 years and low
      relative risks (1.5). Based on relative risks of glioma by tumour latency and
      cumulative hours of phone use in the Swedish study, predicted rates should have
      been at least 40% higher than observed rates in 2008. However, predicted glioma
      rates based on the small proportion of highly exposed people in the Interphone
      study could be consistent with the observed data. Results remained valid if we
      used either non-regular users or low users of mobile phones as the baseline
      category, and if we constrained relative risks to be more than 1. CONCLUSIONS:
      Raised risks of glioma with mobile phone use, as reported by one (Swedish) study
      forming the basis of the IARC's re-evaluation of mobile phone exposure, are not
      consistent with observed incidence trends in US population data, although the US
      data could be consistent with the modest excess risks in the Interphone study.

PMID- 22403264
TI  - Wind turbine noise.

PMID- 22403265
TI  - British and Danish surgeons advise against using dangerous hips.

PMID- 22403266
TI  - China is urged to compensate people infected with HIV through illegal blood
      selling.

PMID- 22403267
TI  - Risk of atrial fibrillation and stroke in rheumatoid arthritis: Danish nationwide
      cohort study.
AB  - OBJECTIVES: To determine if patients with rheumatoid arthritis have increased
      risk of atrial fibrillation and stroke. DESIGN: Longitudinal nationwide register
      based cohort study. SETTING: Inpatient and outpatient hospital care in Denmark
      from 1997 to 2009. PARTICIPANTS: Entire Danish population aged over 15 years
      without rheumatoid arthritis, atrial fibrillation, or stroke before 1997.
      Participants with rheumatoid arthritis were identified by individual level
      linkage of diagnoses and rheumatoid arthritis treatment. MAIN OUTCOME MEASURES:
      Rates of atrial fibrillation and stroke. RESULTS: Of 4,182,335 participants
      included in the cohort, 18,247 were identified as having rheumatoid arthritis
      during follow-up, with a mean age at disease onset of 59.2 years and a median
      follow-up of 4.8 years. A total of 156,484 people, including 774 with rheumatoid
      arthritis, were diagnosed as having atrial fibrillation (age and sex matched
      event rates of 8.2 per 1000 person years in rheumatoid arthritis patients and 6.0
      per 1000 person years in the general population), with an adjusted incidence rate
      ratio of 1.41 (95% confidence interval 1.31 to 1.51). In addition, 165,343
      people, including 718 with rheumatoid arthritis, had a stroke (7.6 per 1000
      person years in rheumatoid arthritis and 5.7 per 1000 person years in the general
      population), with a resultant rate ratio of 1.32 (1.22 to 1.42). For both atrial
      fibrillation and stroke, relative risks were increased in all strata based on
      thirds of sex and age, with higher relative risks in younger patients but higher
      absolute risk differences in older patients. CONCLUSIONS: Rheumatoid arthritis
      was associated with an increased incidence of atrial fibrillation and stroke. The
      novel finding of increased risk of atrial fibrillation in rheumatoid arthritis
      suggests that this arrhythmia is relevant in cardiovascular risk assessment of
      these patients.

PMID- 22403268
TI  - Health and Social Care Bill 2011: a legal basis for charging and providing fewer
      health services to people in England.

PMID- 22403269
TI  - Hepatitis C virus infection and kidney disease: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) infection and kidney disease
      are both highly prevalent diseases. The association between HCV and GN has been
      supported by previous research but little is known about the relationship between
      HCV and kidney disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A
      systematic review of the published medical literature was conducted to determine
      if HCV is associated with increased likelihood of kidney disease in the general
      population. A random-effects model was used to generate a summary estimate of the
      relative risk for kidney disease, defined as an estimated GFR <60 ml/min per 1.73
      m(2) or proteinuria, with HCV across the published studies. RESULTS: Nine
      clinical studies (817,917 unique individuals) were identified. Pooling of study
      results demonstrated the absence of a relationship between HCV seropositive
      status and reduced estimated GFR (adjusted relative risk, 1.12; 95% confidence
      interval, 0.91, 1.38; P=0.28) according to the random-effects model. HCV
      seropositive serology was an independent and significant risk factor for
      proteinuria (defined by urine dipstick test or spot urine albumin/creatinine
      ratio) in the general population, with a summary estimate for adjusted relative
      risk of 1.47 (95% confidence interval, 1.12, 1.94; P=0.006). Significant
      heterogeneity was observed between studies (Ri=0.82; P value by Q test, <0.001).
      CONCLUSIONS: This meta-analysis shows that HCV is independently associated with
      proteinuria but not with reduced GFR in the general population. Substantial
      heterogeneity occurred.

PMID- 22403270
TI  - Finding a common language for patient safety in CKD.
AB  - Improving patient safety has become a primary objective of health systems;
      however, the frequency of adverse safety events continues to be unacceptable
      despite the attention and dedicated efforts of many stakeholders. CKD that does
      not require dialysis increases the risk for adverse safety events, and adverse
      safety events can account for a substantial portion of the poor outcomes typical
      of CKD. Because much of CKD care occurs outside the typical health care setting,
      systems designed to detect and reduce adverse safety events are not necessarily
      effective in this population. Underrecognition (or underappreciation) of CKD and
      the associated impairment of renal function contribute to the high risk for
      adverse safety events. Medication errors are common in CKD and account for many
      lapses in patient safety, but a wide range of other potentially modifiable care
      processes in CKD also contribute to the high rate of observed adverse safety
      events. This review describes the spectrum of safety concerns specific to CKD and
      the need for a common set of standards to improve on current general constructs
      and to reduce adverse safety events in this chronic disease. An accepted set of
      disease-specific indicators is necessary to gauge the extent of the disease
      specific patient safety problem and to design means to reduce adverse safety
      events and improve outcomes in CKD.

PMID- 22403271
TI  - Modifiable practices associated with sudden death among hemodialysis patients in
      the Dialysis Outcomes and Practice Patterns Study.
AB  - BACKGROUND AND OBJECTIVES: Sudden death is common in hemodialysis patients, but
      whether modifiable practices affect the risk of sudden death remains unclear.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study analyzed 37,765
      participants in 12 countries in the Dialysis Outcomes and Practice Patterns Study
      to explore the association of the following practices with sudden death (due to
      cardiac arrhythmia, cardiac arrest, and/or hyperkalemia): treatment time [TT]
      <210 minutes, Kt/V <1.2, ultrafiltration volume >5.7% of postdialysis weight, low
      dialysate potassium [K(D) <3]), and prescription of Q wave/T wave interval
      prolonging drugs. Cox regression was used to estimate effects on mortality,
      adjusting for potential confounders. An instrumental variable approach was used
      to further control for unmeasured patient-level confounding. RESULTS: There were
      9046 deaths, 26% of which were sudden (crude mortality rate, 15.3/100 patient
      years; median follow-up, 1.59 years). Associations with sudden death included
      hazard ratios of 1.13 for short TT, 1.15 for large ultrafiltration volume, and
      1.10 for low Kt/V. Compared with K(D) >=3 mEq/L, the sudden death rate was higher
      for K(D) <=1.5 and K(D)=2-2.5 mEq/L. The instrumental variable approach yielded
      generally consistent findings. The sudden death rate was elevated for patients
      taking amiodarone, but not other Q wave/T wave interval-prolonging drugs.
      CONCLUSIONS: This study identified modifiable dialysis practices associated with
      higher risk of sudden death, including short TT, large ultrafiltration volume,
      and low K(D). Because K(D) <3 mEq/L is common and easy to change, K(D) tailoring
      may prevent some sudden deaths. This hypothesis merits testing in clinical
      trials.

PMID- 22403272
TI  - Differential diagnosis of nongap metabolic acidosis: value of a systematic
      approach.
AB  - Nongap metabolic acidosis is a common form of both acute and chronic metabolic
      acidosis. Because derangements in renal acid-base regulation are a common cause
      of nongap metabolic acidosis, studies to evaluate renal acidification often serve
      as the mainstay of differential diagnosis. However, in many cases, information
      obtained from the history and physical examination, evaluation of the electrolyte
      pattern (to determine if a nongap acidosis alone or a combined nongap and high
      anion gap metabolic acidosis is present), and examination of the serum potassium
      concentration (to characterize the disorder as hyperkalemic or hypokalemic in
      nature) is sufficient to make a presumptive diagnosis without more sophisticated
      studies. If this information proves insufficient, indirect estimates or direct
      measurement of urinary NH(4)(+) concentration, measurement of urine pH, and
      assessment of urinary HCO(3)(-) excretion can help in establishing the diagnosis.
      This review summarizes current information concerning the pathophysiology of this
      electrolyte pattern and the value and limitations of all of the diagnostic
      studies available. It also provides a systematic and cost-effective approach to
      the differential diagnosis of nongap metabolic acidosis.

PMID- 22403273
TI  - PTH--a particularly tricky hormone: why measure it at all in kidney patients?
AB  - Plasma parathyroid hormone (PTH) concentrations are commonly measured in the
      context of CKD, as PTH concentration elevation is typical in this clinical
      context. Much has been inferred from this raised PTH concentration tendency, both
      about the state of skeletal integrity and health and also about the potential
      clinical outcomes for patients. However, we feel that reliance on PTH
      concentrations alone is a dangerous substitute for the search for, and use of,
      more precise and reliable biomarkers. In this article, we rehearse these
      arguments, bringing together patient-level and analytical considerations for the
      first time.

PMID- 22403274
TI  - Low glomerular density with glomerulomegaly in obesity-related glomerulopathy.
AB  - BACKGROUND AND OBJECTIVES: Obesity-related glomerulopathy is a secondary form of
      glomerular disease that may occur in obese individuals. It is histologically
      characterized by marked glomerulomegaly closely related to glomerular
      hyperfiltration. This study examined glomerular density (nonsclerotic glomerular
      number per renal cortical area of biopsy specimen) in patients with obesity
      related glomerulopathy to determine whether any differences in this measure is
      associated with disease status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      Glomerular density and glomerular volume in renal biopsy samples from patients
      with obesity-related glomerulopathy were compared with those of kidney transplant
      donors and patients with IgA nephropathy. Kidneys obtained from persons without
      renal diseases during autopsy were also analyzed to investigate the effects of
      obesity on glomerular density and glomerular volume. RESULTS: Glomerular density
      of kidneys from patients with obesity-related glomerulopathy (1.7+/-0.6/mm(2))
      was significantly lower than that in biopsy samples from kidney transplant donors
      (3.1+/-1.0/mm(2)) and patients with IgA nephropathy (3.5+/-1.5/mm(2)). However,
      an analysis of autopsy cases without renal diseases showed that the glomerular
      density in overweight (2.9+/-0.7/mm(2)) or obese (3.1+/-1.1/mm(2)) persons was
      similar to that in nonobese (3.1+/-0.6/mm(2)) individuals. Biopsy specimens of
      patients with obesity-related glomerulopathy showed marked glomerulomegaly.
      However, glomerular volume was only modestly increased in the autopsy-examined
      kidneys from overweight or obese persons without renal diseases. CONCLUSIONS: Low
      glomerular density associated with glomerulomegaly may be a characteristic
      histologic finding of patients with obesity-related glomerulopathy.

PMID- 22403275
TI  - Patient education to reduce disparities in renal transplantation.

PMID- 22403276
TI  - Efficacy and tolerance of urea compared with vaptans for long-term treatment of
      patients with SIADH.
AB  - BACKGROUND AND OBJECTIVES: Vaptans (vasopressin V(2)-receptor antagonists) are a
      new approach for the treatment of hyponatremia. However, their indications remain
      to be determined, and their benefit compared with that of the usual treatments
      for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) have not
      been evaluated. This prospective, long-term study compared the efficacy,
      tolerability, and safety of two oral vaptans with those of oral urea in patients
      with SIADH. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with chronic
      SIADH of various origins were treated first with vaptans for 1 year. After an 8
      day holiday period, they received oral urea for an additional 1-year follow-up.
      Serum sodium was measured every 2 months, and drug doses were adjusted
      accordingly. RESULTS: Thirteen participants were initially included in the study
      (serum sodium, 125+/-3 mEq/L); 12 completed the 2-year treatment period.
      Treatment with vaptans (satavaptan, 5-50 mg/d, n=10; tolvaptan, 30-60 mg/day,
      n=2) increased natremia (serum sodium, 135+/-3 mEq/L) during the 1-year vaptan
      period without escape. Hyponatremia recurred in the 12 participants when vaptans
      were stopped (holiday period). Urea improved the natremia with the same efficacy
      (serum sodium, 135+/-2 mEq/L) as vaptans during the 1-year urea treatment period.
      One participant treated with tolvaptan withdrew from the study early because of
      excessive thirst. Another patient receiving urea developed hypernatremia without
      complications. CONCLUSIONS: Urea has efficacy similar to that of vaptans for
      treatment of chronic SIADH. Tolerance is generally good for both agents.

PMID- 22403277
TI  - Attending rounds: an older patient with nephrotic syndrome.
AB  - Nephrotic syndrome in older adult patients is a common clinical conundrum.
      Membranous nephropathy (MN) is a lesion frequently found to underlie the
      nephrotic state in such patients. Determining with reasonable certainty whether
      the nephrotic syndrome and MN is primary (idiopathic) or due to an underlying
      disease such as neoplasia can be a daunting clinical challenge. By way of a
      presentation of an illustrative case and a focused review of the relevant
      literature, the approach to evaluation of such patients, with an emphasis on the
      putative causative role of neoplasia in MN, is analyzed and a potential
      contemporary pathway for acquiring the correct diagnosis is offered.

PMID- 22403278
TI  - Eculizumab for dense deposit disease and C3 glomerulonephritis.
AB  - BACKGROUND AND OBJECTIVES: The principle defect in dense deposit disease and C3
      glomerulonephritis is hyperactivity of the alternative complement pathway.
      Eculizumab, a monoclonal antibody that binds to C5 to prevent formation of the
      membrane attack complex, may prove beneficial. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: In this open-label, proof of concept efficacy and safety study, six
      subjects with dense deposit disease or C3 glomerulonephritis were treated with
      eculizumab every other week for 1 year. All had proteinuria >1 g/d and/or AKI at
      enrollment. Subjects underwent biopsy before enrollment and repeat biopsy at the
      1-year mark. RESULTS: The subjects included three patients with dense deposit
      disease (including one patient with recurrent dense deposit disease in allograft)
      and three patients with C3 glomerulonephritis (including two patients with
      recurrent C3 glomerulonephritis in allograft). Genetic and complement function
      testing revealed a mutation in CFH and MCP in one subject each, C3 nephritic
      factor in three subjects, and elevated levels of serum membrane attack complex in
      three subjects. After 12 months, two subjects showed significantly reduced serum
      creatinine, one subject achieved marked reduction in proteinuria, and one subject
      had stable laboratory parameters but histopathologic improvements. Elevated serum
      membrane attack complex levels normalized on therapy and paralleled improvements
      in creatinine and proteinuria. CONCLUSIONS: Clinical and histopathologic data
      suggest a response to eculizumab in some but not all subjects with dense deposit
      disease and C3 glomerulonephritis. Elevation of serum membrane attack complex
      before treatment may predict response. Additional research is needed to define
      the subgroup of dense deposit disease/C3 glomerulonephritis patients in whom
      eculizumab therapy can be considered.

PMID- 22403279
TI  - Effects of icariside II on improving erectile function in rats with
      streptozotocin-induced diabetes.
AB  - Icariin and icariside II (ICA II), 2 active components isolated from herba 
      epimedii, have a closely structural relationship. There is evidence that  icariin
      may be useful in the treatment of erectile dysfunction (ED); however,  the study
      on the therapeutic efficacy of ICA II on ED is currently scant. We  investigated
      the effects of ICA II on improving erectile function of rats with  streptozocin
      induced diabetes. Fifty 8-week-old Sprague-Dawley rats were  randomly distributed
      into normal control and diabetic groups. Diabetes was  induced by a one-time
      intraperitoneal injection of streptozocin (60 mg/kg).  Three days later, the
      diabetic rats were randomly divided into 4 groups  including a saline-treated
      placebo arm and 3 ICA II-treated models (1, 5, and  10 mg/kg/d). After 3 months,
      penile hemodynamics was measured by cavernous  nerve electrostimulation (CNE)
      with real time intracorporal pressure  assessment. Penises were harvested with
      subsequent histological examination  (picrosirius red stain, Hart elastin stain,
      and immunohistochemical stain) and  Western blots to explore the expression of
      the nitric oxide-cyclic guanosine  monophosphate (NO-cGMP) and transforming
      growth factor beta1  (TGFbeta1)/Smad2 signaling pathways. Diabetes significantly
      attenuated  erectile responses to CNE. Diabetic rats had decreased corpus
      cavernosum  smooth muscle/collagen ratio and endothelial cell content relative to
      the  control group. The ratio of collagen I to III was significantly lower in the
      corpora of diabetic rats; furthermore, cavernous elastic fibers were  fragmented
      in the diabetic animals. Neuronal nitric oxide synthase (nNOS),  endothelial
      nitric oxide synthase, and vascular endothelial growth factor were  expressed at
      lower levels in the diabetic group; ICA II-treated diabetic rats  had higher
      expression in the penis relative to placebo-treated diabetic  animals. Both the
      TGFbeta1/Smad2/connective tissue growth factor (CTGF)  signaling pathway and
      apoptosis were down-regulated in the penis from ICA  II-treated rats. ICA II
      treatment attenuates diabetes-related impairment of  penile hemodynamics, likely
      by increasing smooth muscle, endothelial function,  and nNOS expression. ICA II
      could alter corpus cavernosum fibrous-muscular  pathological structure in
      diabetic rats, which could be regulated by the  TGFbeta1/Smad2/CTGF and NO-cGMP
      signaling pathways.

PMID- 22403280
TI  - Penile methadone injection in suicidal intent: life-threatening and fatal for
      erectile function.
AB  - We present the case of a 31-year-old man who was admitted to our emergency 
      department after injection of 10 mL of methadone into his penis. He had a 
      history of drug abuse over the last 15 years and a background of 3 attempted 
      suicidal episodes with a combination of at least 2 drugs over the past 12 
      months. The current suicide attempt had serious consequences: he suffered from 
      acute renal and liver failure. One previously unreported side effect of 
      methadone is erectile dysfunction following injection into the penis. In our 
      case, the patient received vardenafil 10 mg once daily without any signs of 
      functional improvement. Ten months after the event, there still was complete 
      erectile dysfunction.

PMID- 22403281
TI  - Involvement of Fas/Fas-L and Bax/Bcl-2 systems in germ cell death following
      immunization with syngeneic testicular germ cells in mice.
AB  - Experimental autoimmune orchitis (EAO) is characterized by T cell-dependent 
      lymphocytic inflammation and seminiferous tubule damage, which can result in  the
      death of germ cells. The aim of the present study is to investigate the  roles of
      the Fas/Fas-L and Bax/Bcl-2 systems in the death of germ cells in  mice with EAO
      that is induced by immunization with syngeneic testicular germ  cells (TGC). The
      results using real-time reverse transcription-polymerase  chain reaction and
      immunostaining show that many terminal deoxynucleotidyl  transferase-mediated
      dUTP nick-end labeling staining germ cells were present  in seminiferous tubules
      during the active inflammation stage, and these cells  were persistently observed
      in the seminiferous epithelium until the postactive  inflammation stage.
      Intratesticular mRNA expression levels of both Fas and Bax  were increased during
      the active inflammation stage and were dramatically  decreased during the post
      active inflammation stage. In contrast, the  intratesticular mRNA expression
      levels of both Fas-L and Bcl-2 did not show  significant changes during the
      active inflammation stage but showed extreme  increases during the post-active
      inflammation stage. Immunohistochemically,  some Fas- and Bax-positive germ cells
      were detected during the active  inflammation stage, but these were hardly found
      during the post-active  inflammation stage. In contrast, some Fas-L- and Bcl-2
      positive germ cells  were found during the active inflammation stage, and many of
      these were also  observed during the post-active inflammation stage. These
      results indicate  that germ cell death during TGC-induced EAO is mediated by the
      Fas/Fas-L and  Bax/Bcl-2 systems during the active inflammation stage but not
      during the  post-active inflammation stage.

PMID- 22403282
TI  - Surgical treatment of hemangioma on the dorsum of the penis.
AB  - Therapies for hemangiomas of the penis include surgical excision, 
      electrofulguration, cryotherapy, sclerotherapy, and neodymium:yttrium aluminum 
      garnet laser treatment. Urologists often face difficulties in deciding whether 
      to use surgery in penile hemangioma cases. In this study, we investigated the 
      safety and feasibility of surgical treatment of hemangioma in the penis. The 
      study included 6 patients, 19 to 42 years of age (median age 23 years), with 
      hemangiomas on the dorsal aspect of the penis. All patients were treated with 
      surgery. All operations were successful, and no complications were observed. 
      Patients were followed up for 2 to 5 years (median 2.5 years) after discharge 
      from the hospital. Five patients were assessed for sexual function. Lesions 
      healed completely, and all patients were satisfied with the aesthetic results. 
      All patients had returned to normal sexual activity within 3 months of the 
      operation. Sexual function and sexual satisfaction were well maintained after 
      the operation. A therapeutic reference standard for the treatment of penile 
      hemangioma is still lacking because of the rarity of the disease. The results  of
      our experience confirm that surgical treatment for penile hemangioma  represents
      a safe radical curative procedure. Surgical treatment offers an  alternative to
      the more conservative therapy previously advocated.

PMID- 22403283
TI  - Human sperm chromatin undergoes physiological remodeling during in vitro
      capacitation and acrosome reaction.
AB  - Capacitation (CAP) and acrosome reaction (AR) are sequential processes of  sperm
      activation. Beside the known ionic, membrane, and transduction events  and final
      release of proteolytic enzymes that help sperm movement toward the  egg,
      chromatin changes, such as a physiological remodeling, are also possible.  Our
      aims were to ascertain that CAP and AR do not induce DNA damage and to  evaluate
      changes occurring in the human sperm head during these physiological  processes
      using cytochemical stains. Percollpurified spermatozoa from normal  donors were
      incubated in Biggers, Whitten, and Whittingham medium +/-  fetal cord serum
      ultrafiltrate (CAP inducer) and then with  lysophosphatidylcholine (AR inducer).
      CAP and AR were associated with  increases in aniline blue (AB, for histones;
      ~70%) and toluidine blue (TB,  for chromatin compaction; ~40%) staining but had
      no influence on that of  chromomycin A3 (for protamines). The increase (~40%) in 
      iodoacetamide-fluorescein (IAF, for sulfhydryl groups) staining observed  during
      CAP was absent after AR. CAP and AR did not damage DNA (percentage of  DNA
      fragmentation index remained low) nor affect histone content. CAP, and  even more
      AR, primed sperm heads to decondense (~80% and ~140%  increases, respectively)
      when challenged with sodium dodecyl sulfate +  dithiothreitol. Interestingly,
      induced decondensation correlated with all  other tests (CAP, AB, TB, and IAF).
      Therefore, the data strongly support a  physiological remodeling of nondamaged
      human sperm chromatin during CAP and  AR, and modifications are probably
      interlinked and help prepare chromatin for  postfertilization events.

PMID- 22403284
TI  - Gene therapy with an erythropoietin enhancer-mediated, hypoxia-inducible gene
      expression system in the corpus cavernosum of mice with high-cholesterol diet
      induced erectile dysfunction.
AB  - Cavernous hypoxia is an important factor in the pathogenesis of vasculogenic
      erectile dysfunction (ED). Therefore, the hypoxia-inducible gene expression
      system can be exploited as gene therapy for vasculogenic ED. This study was
      undertaken to examine the effectiveness of a hypoxia-inducible gene expression
      system, namely, the RTP801 promoter or the erythropoietin enhancer, in a mouse
      model of hypercholesterolemic ED in vivo and in primary cultured mouse cavernous
      endothelial cells in vitro. Two-month-old male C57BL/6 mice were fed a diet
      containing 4% cholesterol and 1% cholic acid, and age-matched control animals
      were fed a normal diet for 3 months. Mouse cavernous endothelial cells were
      isolated and cultured under normoxic or hypoxic conditions. After treatment of
      animals or endothelial cells with pSV-Luc, pRTP801-Luc, or pEpo-SV-Luc vector,
      gene expression was evaluated by luciferase assay, and the gene expression area
      was evaluated by immunohistochemistry. Plasmids pRTP801-Luc and pEpo-SV-Luc
      induced gene expression significantly in the hypercholesterolemic mice and in
      cavernous endothelial cells under hypoxia, and the highest gene expression was
      noted in the group treated with pEpo-SV-Luc. Gene expression was higher for more
      than 7 days in the hypercholesterolemic mice injected with pEpo-SV-Luc than in
      mice injected with pSV-Luc. As shown by immunohistochemistry, the gene expression
      area was also greater in the pEpo-SV-Luc group than in the pSV-Luc group, but the
      difference was not as great as that in luciferase activity. The hypoxia-specific
      gene expression system could be a valuable tool for facilitating gene delivery
      into ischemic corpus cavernosum tissue resulting from vascular causes.

PMID- 22403285
TI  - Pharmacokinetic evaluation and dosing of subcutaneous testosterone pellets.
AB  - Subcutaneous testosterone (T) pellets are a viable treatment modality for
      hypogonadism. Optimal dosing, frequency of reimplantation, and long-term safety
      of T pellets remain incompletely elucidated parameters. A retrospective review of
      273 patients treated for hypogonadism using subcutaneous T pellets was performed.
      Serum total T (TT), free T (FT), and estradiol (E2) levels were analyzed as a
      function of time from implantation, number of pellets implanted (6-9 or 10-12),
      body mass index (BMI; <25 or >= 25 kg/m(2)), number of implantations (<= 4
      rounds, 501 insertions), and preimplantation T levels (<300 or >= 300 ng/dL). T
      decay was determined using linear regression and TT levels immediately
      postimplantation and the time for TT levels to reach 300 ng/dL extrapolated for
      all variables. Mean patient age +/- SD was 56 +/- 12.6 years. Baseline TT level
      was 328 +/- 202 ng/dL, FT 9.49 +/- 27.8 pg/mL, and E2 25.1 +/- 17.3 pg/mL.
      Extrapolated TT and FT peaks were lower in men receiving 6 to 9 pellets than men
      receiving 10 to 12, although decay rates differed insignificantly. E2 levels rose
      significantly in men receiving 10 to 12 but not 6 to 9 pellets. Men with BMI >=
      25 kg/m(2) attained lower TT peaks with slower decay than men with BMI <25
      kg/m(2) receiving 10 to 12 pellets, although 300 ng/dL TT levels were reached at
      approximately 100 days in both groups. No differences were seen in decay rates
      for men with multiple implant rounds, and no differences in T peaks or decay
      rates were seen in men with preimplant T level <300 or >= 300 ng/dL. One patient
      developed erythrocytosis, and no prostate-specific antigen recurrences were
      observed in men with prostate cancer treated with T pellets. Men with BMI <25
      kg/m(2) should receive fewer pellets, and reimplantation for all men should occur
      100 to 120 days after prior implantation. Men receiving 10 to 12 pellets have
      higher E2 levels, potentially reflecting increased aromatization of T.
      Reimplantation and preimplantation TT levels do not affect pellet decay kinetics.

PMID- 22403286
TI  - CPPsite: a curated database of cell penetrating peptides.
AB  - Delivering drug molecules into the cell is one of the major challenges in the
      process of drug development. In past, cell penetrating peptides have been
      successfully used for delivering a wide variety of therapeutic molecules into
      various types of cells for the treatment of multiple diseases. These peptides
      have unique ability to gain access to the interior of almost any type of cell.
      Due to the huge therapeutic applications of CPPs, we have built a comprehensive
      database 'CPPsite', of cell penetrating peptides, where information is compiled
      from the literature and patents. CPPsite is a manually curated database of
      experimentally validated 843 CPPs. Each entry provides information of a peptide
      that includes ID, PubMed ID, peptide name, peptide sequence, chirality, origin,
      nature of peptide, sub-cellular localization, uptake efficiency, uptake
      mechanism, hydrophobicity, amino acid frequency and composition, etc. A wide
      range of user-friendly tools have been incorporated in this database like
      searching, browsing, analyzing, mapping tools. In addition, we have derived
      various types of information from these peptide sequences that include
      secondary/tertiary structure, amino acid composition and physicochemical
      properties of peptides. This database will be very useful for developing models
      for predicting effective cell penetrating peptides. Database URL:
      http://crdd.osdd.net/raghava/cppsite/.

PMID- 22403287
TI  - Mothers and babies benefit from smoking ban.

PMID- 22403288
TI  - Basic healthcare needs of care home residents are being neglected by
      commissioners.

PMID- 22403289
TI  - Co-author of Wakefield paper on MMR vaccine wins his appeal against decision by
      GMC to strike him off.

PMID- 22403290
TI  - Learn from AIDS and invest in dementia care now to save money later, conference
      hears.

PMID- 22403291
TI  - Be wary of signing deals for telehealth technologies, conference hears.

PMID- 22403292
TI  - Scottish physicians withdraw their support for health bill in England.

PMID- 22403293
TI  - Doctors renew call for "obstinate government" to abandon health bill.

PMID- 22403294
TI  - A fully human, allosteric monoclonal antibody that activates the insulin receptor
      and improves glycemic control.
AB  - Many patients with diabetes mellitus (both type 1 and type 2) require therapy to
      maintain normal fasting glucose levels. To develop a novel treatment for these
      individuals, we used phage display technology to target the insulin receptor
      (INSR) complexed with insulin and identified a high affinity, allosteric, human
      monoclonal antibody, XMetA, which mimicked the glucoregulatory, but not the
      mitogenic, actions of insulin. Biophysical studies with cultured cells expressing
      human INSR demonstrated that XMetA acted allosterically and did not compete with
      insulin for binding to its receptor. XMetA was found to function as a specific
      partial agonist of INSR, eliciting tyrosine phosphorylation of INSR but not the
      IGF-IR. Although this antibody activated metabolic signaling, leading to enhanced
      glucose uptake, it neither activated Erk nor induced proliferation of cancer
      cells. In an insulin resistant, insulinopenic model of diabetes, XMetA markedly
      reduced elevated fasting blood glucose and normalized glucose tolerance. After 6
      weeks, significant improvements in HbA(1c), dyslipidemia, and other
      manifestations of diabetes were observed. It is noteworthy that hypoglycemia and
      weight gain were not observed during these studies. These studies indicate,
      therefore, that allosteric monoclonal antibodies have the potential to be novel,
      ultra-long acting, agents for the regulation of hyperglycemia in diabetes.

PMID- 22403295
TI  - Adoptive transfer with in vitro expanded human regulatory T cells protects
      against porcine islet xenograft rejection via interleukin-10 in humanized mice.
AB  - T cell-mediated rejection remains a barrier to the clinical application of islet
      xenotransplantation. Regulatory T cells (Treg) regulate immune responses by
      suppressing effector T cells. This study aimed to determine the ability of human
      Treg to prevent islet xenograft rejection and the mechanism(s) involved. Neonatal
      porcine islet transplanted NOD-SCID IL2rgamma(-/-) mice received human peripheral
      blood mononuclear cells (PBMC) with in vitro expanded autologous Treg in the
      absence or presence of anti-human interleukin-10 (IL-10) monoclonal antibody. In
      addition, human PBMC-reconstituted recipient mice received recombinant human IL
      10 (rhIL-10). Adoptive transfer with expanded autologous Treg prevented islet
      xenograft rejection in human PBMC-reconstituted mice by inhibiting graft
      infiltration of effector cells and their function. Neutralization of human IL-10
      shortened xenograft survival in mice receiving human PBMC and Treg. In addition,
      rhIL-10 treatment led to prolonged xenograft survival in human PBMC-reconstituted
      mice. This study demonstrates the ability of human Treg to prevent T-cell
      effector function and the importance of IL-10 in this response. In vitro Treg
      expansion was a simple and effective strategy for generating autologous Treg and
      highlighted a potential adoptive Treg cell therapy to suppress antigraft T-cell
      responses and reduce the requirement for immunosuppression in islet
      xenotransplantation.

PMID- 22403296
TI  - Following the fate of one insulin-reactive CD4 T cell: conversion into Teffs and
      Tregs in the periphery controls diabetes in NOD mice.
AB  - In diabetic patients and susceptible mice, insulin is a targeted autoantigen.
      Insulin B chain 9-23 (B:9-23) autoreactive CD4 T cells are key for initiating
      autoimmune diabetes in NOD mice; however, little is known regarding their origin
      and function. To this end, B:9-23-specific, BDC12-4.1 T-cell receptor (TCR)
      transgenic (Tg) mice were studied, of which, despite expressing a single TCR on
      the recombination activating gene-deficient background, only a fraction develops
      diabetes in an asynchronous manner. BDC12-4.1 CD4 T cells convert into effector
      (Teff) and Foxp3(+)-expressing adaptive regulatory T cells (aTregs) soon after
      leaving the thymus as a result of antigen recognition and homeostatic
      proliferation. The generation of aTreg causes the heterogeneous diabetes onset,
      since crossing onto the scurfy (Foxp3) mutation, BDC12-4.1 TCR Tg mice develop
      accelerated and fully penetrant diabetes. Similarly, adoptive transfer and bone
      marrow transplantation experiments showed differential diabetes kinetics based on
      Foxp3(+) aTreg's presence in the BDC12-4.1 donors. A single-specificity, insulin
      reactive TCR escapes thymic deletion and simultaneously converts into aTreg and
      Teff, establishing an equilibrium that determines diabetes penetrance. These
      results are of particular importance for understanding disease pathogenesis. They
      suggest that once central tolerance is bypassed, autoreactive cells arriving in
      the periphery do not by default follow solely a pathogenic fate upon activation.

PMID- 22403297
TI  - GLUT4 and glycogen synthase are key players in bed rest-induced insulin
      resistance.
AB  - To elucidate the molecular mechanisms behind physical inactivity-induced insulin
      resistance in skeletal muscle, 12 young, healthy male subjects completed 7 days
      of bed rest with vastus lateralis muscle biopsies obtained before and after. In
      six of the subjects, muscle biopsies were taken from both legs before and after a
      3-h hyperinsulinemic euglycemic clamp performed 3 h after a 45-min, one-legged
      exercise. Blood samples were obtained from one femoral artery and both femoral
      veins before and during the clamp. Glucose infusion rate and leg glucose
      extraction during the clamp were lower after than before bed rest. This bed rest
      induced insulin resistance occurred together with reduced muscle GLUT4,
      hexokinase II, protein kinase B/Akt1, and Akt2 protein level, and a tendency for
      reduced 3-hydroxyacyl-CoA dehydrogenase activity. The ability of insulin to
      phosphorylate Akt and activate glycogen synthase (GS) was reduced with normal GS
      site 3 but abnormal GS site 2+2a phosphorylation after bed rest. Exercise
      enhanced insulin-stimulated leg glucose extraction both before and after bed
      rest, which was accompanied by higher GS activity in the prior-exercised leg than
      the rested leg. The present findings demonstrate that physical inactivity-induced
      insulin resistance in muscle is associated with lower content/activity of key
      proteins in glucose transport/phosphorylation and storage.

PMID- 22403298
TI  - Enhanced cerebral but not peripheral angiogenesis in the Goto-Kakizaki model of
      type 2 diabetes involves VEGF and peroxynitrite signaling.
AB  - We previously reported enhanced cerebrovascular remodeling and arteriogenesis in
      experimental type 2 diabetes. This study tested the hypotheses that 1) cerebral
      but not peripheral angiogenesis is increased in a spatial manner and 2)
      peroxynitrite orchestrates vascular endothelial growth factor (VEGF)-mediated
      brain angiogenesis in diabetes. Stereology of brain, eye, and skeletal muscle
      microvasculature was evaluated in control and diabetic rats using three
      dimensional images. Migration and tube formation properties of brain
      microvascular endothelial cells (BMECs) were analyzed as markers of angiogenesis.
      Vascular density, volume, and surface area were progressively increased from
      rostral to caudal sections in both the cerebral cortex and striatum in diabetic
      rats. Unperfused new vessels were more prominent and the pericyte-to-endothelial
      cell ratio was decreased in diabetes. Vascularization was greater in the retina
      but lower in the peripheral circulation. VEGF and nitrotyrosine levels were
      higher in cerebral microvessels of diabetic animals. Migratory and tube formation
      properties were enhanced in BMECs from diabetic rats, which also expressed high
      levels of basal VEGF, nitrotyrosine, and membrane-type (MT1) matrix
      metalloprotease (MMP). VEGF-neutralizing antibody and inhibitors of
      peroxynitrite, src kinase, or MMP blocked the migration. Diabetes increases and
      spatially regulates cerebral neovascularization. Increased VEGF-dependent
      angiogenic function in BMECs is mediated by peroxynitrite and involves c-src and
      MT1-MMP activation.

PMID- 22403299
TI  - Peripheral blood monocyte gene expression profile clinically stratifies patients
      with recent-onset type 1 diabetes.
AB  - Novel biomarkers of disease progression after type 1 diabetes onset are needed.
      We profiled peripheral blood (PB) monocyte gene expression in six healthy
      subjects and 16 children with type 1 diabetes diagnosed ~3 months previously and
      analyzed clinical features from diagnosis to 1 year. Monocyte expression profiles
      clustered into two distinct subgroups, representing mild and severe deviation
      from healthy control subjects, along the same continuum. Patients with strongly
      divergent monocyte gene expression had significantly higher insulin dose-adjusted
      HbA(1c) levels during the first year, compared with patients with mild deviation.
      The diabetes-associated expression signature identified multiple perturbations in
      pathways controlling cellular metabolism and survival, including endoplasmic
      reticulum and oxidative stress (e.g., induction of HIF1A, DDIT3, DDIT4, and
      GRP78). Quantitative PCR (qPCR) of a 9-gene panel correlated with glycemic
      control in 12 additional recent-onset patients. The qPCR signature was also
      detected in PB from healthy first-degree relatives. A PB gene expression
      signature correlates with glycemic control in the first year after diabetes
      diagnosis and is present in at-risk subjects. These findings implicate monocyte
      phenotype as a candidate biomarker for disease progression pre- and postonset and
      systemic stresses as contributors to innate immune function in type 1 diabetes.

PMID- 22403300
TI  - The novel therapeutic effect of phosphoinositide 3-kinase-gamma inhibitor
      AS605240 in autoimmune diabetes.
AB  - Type 1 diabetes (T1D) remains a major health problem worldwide, with a steadily
      rising incidence yet no cure. Phosphoinositide 3-kinase-gamma (PI3Kgamma), a
      member of a family of lipid kinases expressed primarily in leukocytes, has been
      the subject of substantial research for its role in inflammatory diseases.
      However, the role of PI3Kgamma inhibition in suppressing autoimmune T1D remains
      to be explored. We tested the role of the PI3Kgamma inhibitor AS605240 in
      preventing and reversing diabetes in NOD mice and assessed the mechanisms by
      which this inhibition abrogates T1D. Our data indicate that the PI3Kgamma pathway
      is highly activated in T1D. In NOD mice, we found upregulated expression of
      phosphorylated Akt (PAkt) in splenocytes. Notably, T regulatory cells (Tregs)
      showed significantly lower expression of PAkt compared with effector T cells.
      Inhibition of the PI3Kgamma pathway by AS605240 efficiently suppressed effector T
      cells and induced Treg expansion through the cAMP response element-binding
      pathway. AS605240 effectively prevented and reversed autoimmune diabetes in NOD
      mice and suppressed T-cell activation and the production of inflammatory
      cytokines by autoreactive T cells in vitro and in vivo. These studies demonstrate
      the key role of the PI3Kgamma pathway in determining the balance of Tregs and
      autoreactive cells regulating autoimmune diabetes.

PMID- 22403301
TI  - Class II histone deacetylases downregulate GLUT4 transcription in response to
      increased cAMP signaling in cultured adipocytes and fasting mice.
AB  - Insulin-mediated glucose uptake is highly sensitive to the levels of the
      facilitative glucose transporter protein, GLUT4. Repression of GLUT4 expression
      is correlated with insulin resistance in adipose tissue. We have shown that
      differentiation-dependent GLUT4 transcription was under control of class II
      histone deacetylases (HDACs). We hypothesized that HDACs may regulate gene
      expression in adipocytes as a result of adrenergic activation. To test this
      hypothesis, we activated cAMP signaling in 3T3-L1 adipocytes and in mice after an
      overnight fast. Chromatin immunoprecipitation experiments showed the association
      of HDAC4/5 with the GLUT4 promoter in vivo and in vitro in response to elevated
      cAMP. Knockdown of HDACs by small interfering RNA in cultured adipocytes
      prevented the cAMP-dependent decrease in GLUT4 transcription. HDAC4/5 recruitment
      to the GLUT4 promoter was dependent on the GLUT4 liver X receptor (LXR) binding
      site. Treatment of cells with an LXR agonist prevented the cAMP-dependent
      decrease in GLUT4 transcription. A loss of function mutation in the LXR response
      element was required for cAMP-dependent downregulation of GLUT4 expression in
      vitro, in fasted mice, and in mice subjected to diet-induced obesity. This
      suggests that activation of LXR signaling can prevent loss of GLUT4 expression in
      diabetes and obesity.

PMID- 22403303
TI  - A 60-year-old man from the highlands of Peru with fever and hemolysis.

PMID- 22403302
TI  - Deep resequencing unveils genetic architecture of ADIPOQ and identifies a novel
      low-frequency variant strongly associated with adiponectin variation.
AB  - Increased adiponectin levels have been shown to be associated with a lower risk
      of type 2 diabetes. To understand the relations between genetic variation at the
      adiponectin-encoding gene, ADIPOQ, and adiponectin levels, and subsequently its
      role in disease, we conducted a deep resequencing experiment of ADIPOQ in 14,002
      subjects, including 12,514 Europeans, 594 African Americans, and 567 Indian
      Asians. We identified 296 single nucleotide polymorphisms (SNPs), including 30
      amino acid changes, and carried out association analyses in a subset of 3,665
      subjects from two independent studies. We confirmed multiple genome-wide
      association study findings and identified a novel association between a low
      frequency SNP (rs17366653) and adiponectin levels (P = 2.2E-17). We show that
      seven SNPs exert independent effects on adiponectin levels. Together, they
      explained 6% of adiponectin variation in our samples. We subsequently assessed
      association between these SNPs and type 2 diabetes in the Genetics of Diabetes
      Audit and Research in Tayside Scotland (GO-DARTS) study, comprised of 5,145 case
      and 6,374 control subjects. No evidence of association with type 2 diabetes was
      found, but we were also unable to exclude the possibility of substantial effects
      (e.g., odds ratio 95% CI for rs7366653 [0.91-1.58]). Further investigation by
      large-scale and well-powered Mendelian randomization studies is warranted.

PMID- 22403304
TI  - Bilateral enlargement of transverse cervical nerve in two patients of leprosy.

PMID- 22403305
TI  - Real-time quantitative reverse transcription PCR for monitoring of blood-stage
      Plasmodium falciparum infections in malaria human challenge trials.
AB  - To detect pre-patent parasitemia, we developed a real-time quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR) for the asexual 18S ribosomal
      RNA (rRNAs) of Plasmodium falciparum. Total nucleic acids extracted from whole
      blood were combined with control RNA and tested by qRT-PCR. The assay quantified
      > 98.7% of parasite-containing samples to +/-0.5 log(10) parasites/mL of the
      nominal value without false positives. The analytical sensitivity was >= 20
      parasites/mL. The coefficient of variation was 0.6% and 1.8% within runs and 1.6%
      and 4.0% between runs for high and low parasitemia specimens, respectively. Using
      this assay, we determined that A-type 18S rRNAs are stably expressed at 1 * 10(4)
      copies per ring-stage parasite. When used to monitor experimental P. falciparum
      infection of human volunteers, the assay detected blood-stage infections 3.7 days
      earlier on average than thick blood smears. This validated, internally controlled
      qRT-PCR method also uses a small (50 MUL) sample volume requiring minimal pre
      analytical handling, making it useful for clinical trials.

PMID- 22403306
TI  - Efficacy of artemether-lumefantrine in area of high malaria endemicity in India
      and its correlation with blood concentration of lumefantrine.
AB  - This study was conducted to correlate blood concentrations of lumefantrine with
      treatment outcome for patients with Plasmodium falciparum malaria when the drug
      was given without specific instructions for administration with food. Patients
      with P. falciparum malaria in the highly endemic state of Orissa, India, were
      enrolled during 2008 and followed-up for 28 days after admistration of artemether
      lumefantrine for three days according to a World Health Organization protocol.
      Drug concentration in whole blood was determined by using blood spots placed on
      filter paper on day 7. The technology is suitable for field studies. One hundred
      percent of the patients had an adequate clinical and parasitological response.
      These results confirm the efficacy of artemether-lumefantrine in persons from
      poor tribal communities when given without specific instructions regarding co
      administration with food, despite high inter-individual variability in blood
      concentrations of lumefantrine.

PMID- 22403307
TI  - Mosquito infection studies with Aotus monkeys and humans infected with the
      Chesson strain of Plasmodiun vivax.
AB  - Oocyst counts were compared between mosquitoes that fed on humans versus
      mosquitoes that fed on Aotus monkeys, both of which were infected with the
      Chesson strain of Plasmodium vivax. Oocyst counts obtained from mosquitoes fed on
      humans were almost 10-fold higher in number. Mosquitoes were more likely to be
      infected and with a higher rate of infection when they fed on monkeys before the
      peak in the asexual parasite count. Mosquitoes that fed on humans were more
      likely to be more heavily infected when fed after the peak in the asexual count.
      Of several species of owl monkeys, Aotus vociferans was infected at a higher
      frequency. On the basis of oocyst counts, Anopheles dirus were the most
      susceptible and An. maculatus were the least susceptible of the mosquito species
      tested.

PMID- 22403308
TI  - No evidence for spread of Plasmodium falciparum artemisinin resistance to
      Savannakhet Province, Southern Laos.
AB  - We conducted an open-label, randomized clinical trial to assess parasite
      clearance times (PCT) and the efficacy of 4 mg/kg (group 1, n = 22) and 2 mg/kg
      (group 2, n = 22) of oral artesunate for three days followed by artemether
      lumefantrine in patients with uncomplicated Plasmodium falciparum malaria at
      Xepon Interdistrict Hospital, Savannakhet Province in southern Laos. Slides were
      read in duplicate. The overall mean (95% confidence interval; range) PCT in hours
      was 23.2 (21.2-25.3; 12-46) and 22.4 (20.3-24.5; 12-46) for the first and second
      microscopists, respectively (P = 0.57). Ten (23%) patients remained parasitemic
      on day 1 after treatment (4 [18%] in group 1 and 6 [27%] in group 2; P = 0.47).
      No patient had patent asexual parasitemia on the second and third days of
      treatment. The 42-day polymerase chain reaction-corrected cure rates were 100% in
      both treatment groups. Serious adverse events did not develop during or after
      treatment in any patients. In conclusion, no evidence of P. falciparum in vivo
      resistance to artesunate was found in southern Laos.

PMID- 22403309
TI  - Successful oral therapy for severe falciparum malaria: the World Health
      Organization criteria revisited.
AB  - We report a successful treatment of severe falciparum malaria in a non-immune
      adult patient with 30% parasitemia treated with the 6-dose oral regimen of
      artemether plus lumefantrine combination therapy alone. We have also
      retrospectively searched our tertiary center's database for similar cases and we
      have found two additional severe malaria cases, resolved uneventfully with oral
      regimen. These cases might indicate a need to specifically address the definition
      of severe and complicated malaria in non-immune patients either in designated
      guidelines or as an explicit addition to the historical World Health Organization
      criteria.

PMID- 22403310
TI  - Identification of a Western blot pattern for the specific diagnosis of
      Trypanosoma cruzi infection in human sera.
AB  - A Western blot (WB) method using a lysate from Trypanosoma cruzi (Maracay strain)
      epimastigotes was evaluated. Serum samples from 37 patients with confirmed Chagas
      disease (cohort I), 27 Spanish patients with visceral leishmaniasis caused by
      Leishmania infantum (cohort II), and 28 Colombian patients with cutaneous
      leishmaniasis caused by L. panamensis and negative serology for Chagas disease
      (cohort III) were tested. The negative controls were 55 healthy seronegative
      subjects for T. cruzi and Leishmania; 28 of the negative controls were from a
      region endemic for Chagas disease and Leishmania (cohort IV), and 27 of the
      negative controls were from a non-endemic area for Leishmania and T. cruzi
      (cohort V). A homogeneous standard band pattern consisting of six antigenic bands
      corresponding to 28, 32, 38, 39, 40, and 48 kDa was recognized simultaneously for
      all Chagasic patients' sera. Sera from Leishmania-infected patients showed a
      heterogeneous band pattern that was easily differentiated from the pattern of
      patients with Chagas disease. WB with T. cruzi epimastigote antigen is an
      efficient method for diagnosis and may be used as an alternative to confirm T.
      cruzi and detect cross-reactivity with Leishmania.

PMID- 22403311
TI  - The economic value of a visceral leishmaniasis vaccine in Bihar state, India.
AB  - Visceral leishmaniasis (VL) is responsible for substantial morbidity and
      mortality and current available treatments have many limitations. The ability of
      VL infection to generate life-long immunity offers promise for the development of
      a VL vaccine. A VL vaccine candidate has recently completed phase I clinical
      trials. We constructed a computer simulation model to determine the potential
      economic value of a VL vaccine in the endemic region of Bihar state, India.
      Results found a potential vaccine to be cost-effective (and in many cases
      economically dominant, i.e., saving costs and providing health benefits)
      throughout a wide range of vaccination costs and vaccine efficacies, and VL
      risks. Overall, our study strongly supports the continued development of a VL
      vaccine.

PMID- 22403312
TI  - Epidemiological and clinical changes in American tegumentary leishmaniasis in an
      area of Leishmania (Viannia) braziliensis transmission over a 20-year period.
AB  - The Health Post of Corte de Pedra is located in a region endemic for American
      tegumentary leishmaniasis (ATL) in the Brazilian state of Bahia, and it treats
      500-1,300 patients annually. To describe temporal changes in the epidemiology of
      ATL, we reviewed a random sample of 10% of patient charts (N = 1,209) from 1988
      to 2008. There was a twofold increase in the number of cases over the 20-year
      period, with fluctuations in 10-year cycles. Patients were most frequently male,
      between the ages of 10 and 30 years, and engaged in agricultural labor; 4.3% of
      patients had mucosal disease, and 2.4% of patients had disseminated disease. Over
      the study period, the number of disseminated cases increased threefold, the
      proportion of cases in younger patients and agricultural workers decreased, and
      the proportion of patients residing in coastal areas increased. ATL is on the
      rise in Bahia, with a 10-year periodicity and evolving changes in epidemiology
      and manifestations of disease.

PMID- 22403313
TI  - Leishmaniasis in the United States: treatment in 2012.
AB  - Although civilian physicians in the United States seldom encounter patients with
      leishmaniasis, therapeutic advances in endemic regions have opened the door to
      approaches that can be applied in this country. Advances revolve around the use
      of oral miltefosine in all forms of leishmaniasis and the use of short-course
      intravenous liposomal amphotericin B in visceral and possibly cutaneous
      infection. Lengthy, traditional intravenous treatment with pentavalent antimony
      (sodium stibogluconate) still has a role in the United States; however, although
      expensive, miltefosine and liposomal amphotericin B are considerably more
      appealing selections for initial therapy.

PMID- 22403314
TI  - Molecular epidemiologic characterization of Enterocytozoon bieneusi in HIV
      infected persons in Benin City, Nigeria.
AB  - Molecular characterization of Enterocytozoon bieneusi has led to better
      understanding of microsporidiosis transmission in humans. This study aimed to
      detect and genotype E. bieneusi in human immunodeficiency virus (HIV)-infected
      persons. Stool specimens were collected from 463 HIV-infected patients and
      analyzed for E. bieneusi by polymerase chain reaction (PCR) and DNA sequence
      analysis of the internal transcribed spacer. E. bieneusi was detected in 77 HIV
      patients. CD4 cell counts < 200 cells/MUL was associated with E. bieneusi
      infection (P = 0.09). E. bieneusi was significantly associated with weight loss
      (P < 0.0001), diarrhea (P = 0.006), fever (P < 0.0001), not being married (P <
      0.0001), and flush type of toilet (P = 0.0007). Six known genotypes of D, A, IV,
      CAF2, EbpA, and Peru 8 in 31, 22, 14, 2, 1, and 1 patients, respectively, five
      novel genotypes of E. bieneusi, and one infection with mixed genotypes were
      observed in this study. Three of the novel genotypes were genetically distant to
      the genotypes commonly found in humans.

PMID- 22403315
TI  - Triatomine infestation in Guatemala: spatial assessment after two rounds of
      vector control.
AB  - In 2000, the Guatemalan Ministry of Health initiated a Chagas disease program to
      control Rhodnius prolixus and Triatoma dimidiata by periodic house spraying with
      pyrethroid insecticides to characterize infestation patterns and analyze the
      contribution of programmatic practices to these patterns. Spatial infestation
      patterns at three time points were identified using the Getis-Ord Gi*(d) test.
      Logistic regression was used to assess predictors of reinfestation after
      pyrethroid insecticide administration. Spatial analysis showed high and low
      clusters of infestation at three time points. After two rounds of spray, 178
      communities persistently fell in high infestation clusters. A time lapse between
      rounds of vector control greater than 6 months was associated with 1.54 (95%
      confidence interval = 1.07-2.23) times increased odds of reinfestation after
      first spray, whereas a time lapse of greater than 1 year was associated with 2.66
      (95% confidence interval = 1.85-3.83) times increased odds of reinfestation after
      first spray compared with localities where the time lapse was less than 180 days.
      The time lapse between rounds of vector control should remain under 1 year.
      Spatial analysis can guide targeted vector control efforts by enabling tracking
      of reinfestation hotspots and improved targeting of resources.

PMID- 22403316
TI  - New discoveries of sylvatic Triatoma infestans (Hemiptera: Reduviidae) throughout
      the Bolivian Chaco.
AB  - Sylvatic populations of Triatoma infestans might be involved in the
      recolonization of human dwellings. We report here the discoveries of new T.
      infestans sylvatic foci in the Bolivian Chaco. Eighty-one triatomines were
      caught, 38 of which were identified as T. infestans. Triatoma sordida and
      Panstrongylus geniculatus were the other species collected. One T. infestans and
      one T. sordida were infected with Trypanosoma cruzi TcI; one T. infestans was
      infected with TcII. These discoveries add to the debate on the geographic
      distribution of sylvatic T. infestans populations, the geographic origin of the
      species, and the epidemiological role of these populations.

PMID- 22403317
TI  - Determinants of Anopheles seasonal distribution patterns across a forest to
      periurban gradient near Iquitos, Peru.
AB  - As part of a field ecology study of arbovirus and malaria activity in the Amazon
      Basin, Loreto Department, Peru, we collected mosquitoes landing on humans at a
      forest site and inside and outside of residences and military barracks at
      periurban, rural, and village sites. We collected 11 Anopheles spp. from these
      four sites. An. darlingi, the principal malaria vector in the region, accounted
      for 98.7% of all Anopheles spp. collected at Puerto Almendra. Peaks in landing
      activity occurred during the December and April collection periods. However, the
      percent of sporozoite-positive Anopheles spp. was highest 1-2 months later, when
      landing activity decreased to approximately 10% of the peak activity periods. At
      all sites, peak landing activity occurred about 2 hours after sunset. These data
      provide a better understanding of the taxonomy, population density, and seasonal
      and habitat distribution of potential malaria vectors within the Amazon Basin
      region.

PMID- 22403318
TI  - Exceptionally high prevalence of infection of Bithynia siamensis goniomphalos
      with Opisthorchis viverrini cercariae in different wetlands in Thailand and Lao
      PDR.
AB  - The carcinogenic liver fluke, Opisthorchis viverrini, requires Bithynia snail
      intermediate hosts in its life cycle. However, the prevalence of O. viverrini in
      snail intermediate hosts is typically low (< 1%). Here, we examined B. siamensis
      goniomphalos from 48 localities in Thailand and The Lao People's Democratic
      Republic (Lao PDR) and reported high-prevalence levels of O. viverrini. The
      highest-prevalence levels per locality were 6.93% (mean = 3.04%) in Thailand and
      8.37% (mean = 2.01%) in Lao PDR; 4 of 13 localities examined showed prevalence
      higher than any prevalence previously recorded. The number of cercariae infecting
      snails and their prevalence were positively correlated with the size of the
      snails. High prevalence occurred in the Songkram River wetland (Thailand) and the
      Nam Ngum River wetland (Lao PDR). Our results show that transmission of O.
      viverrini from humans as well as animal reservoir hosts to snail intermediate
      hosts is ongoing and potentially increasing in endemic areas across Thailand and
      Lao PDR.

PMID- 22403319
TI  - Unifocal bone paracoccidioidomycosis, Brazil.
AB  - We report a 47 year-old man from the State of Mato Grosso do Sul, Brazil, with
      unifocal tibial paracoccidioidomycosis. A radiograph showed an osteolytic lesion
      on the tibial middle third diaphysis. The diagnosis was confirmed by
      histopathologic analysis, and treatment with sulfamethoxazole and trimethoprim
      was started. After three months, the patient showed significant clinical
      improvement. Ten months after treatment, the patient showed lesion bone healing.
      This case describes the rare occurrence of an osteolytic lesion caused by endemic
      Paracoccidioides brasiliensis in Latin America.

PMID- 22403320
TI  - Severe dengue virus infection in pediatric travelers visiting friends and
      relatives after travel to the Caribbean.
AB  - Of eight children given a diagnosis of dengue, a complicated course developed in
      three (38%), including one infant with dengue shock syndrome. Children visiting
      friends and relatives in dengue-endemic regions are at risk for severe dengue
      associated morbidity. Children of families originally from these locations may
      benefit from pre-travel advice and may represent candidates for a future dengue
      vaccine.

PMID- 22403321
TI  - Disseminated Sporothrix brasiliensis infection with endocardial and ocular
      involvement in an HIV-infected patient.
AB  - Disseminated sporotrichosis occurs in individuals with impaired cellular
      immunity, such as in cases of neoplasia, transplantation, diabetes, and
      especially, acquired immunodeficiency syndrome. This report presents a 32-year
      old Brazilian human immunodeficiency virus (HIV)-infected patient who developed a
      protracted condition of disseminated sporotrichosis with endocarditis, bilateral
      endophthalmitis, and lymphatic involvement. He needed cardiac surgery to replace
      the mitral valve. Sporothrix brasiliensis isolates were recovered from cultures
      of subcutaneous nodules and mitral valve fragments. Species identification was
      based on classical and molecular methods. The patient received amphotericin B for
      52 days and subsequently, oral itraconazole. He remains asymptomatic, and he is
      on maintenance therapy with itraconazole. Despite his positive clinical outcome,
      he developed bilateral blindness. To our knowledge, this case is the first report
      of endocarditis and endophthalmitis caused by S. brasiliensis.

PMID- 22403322
TI  - Burden of Fasciola hepatica Infection among children from Paucartambo in Cusco,
      Peru.
AB  - There is a high prevalence of fascioliasis in the Peruvian highlands, but most
      cases remain undiagnosed. The burden of disease caused by chronic subclinical
      infection is largely unknown. We studied school-age children from a district in
      Paucartambo Province in Cusco, Peru to evaluate the burden of disease caused by
      subclinical fascioliasis. Parasite eggs and/or larvae were identified in 46.2% of
      subjects, including Fasciola hepatica in 10.3% of subjects. Fascioliasis was
      independently associated with anemia (adjusted odds ratio = 3.01 [1.10-8.23]).
      Subclinical fascioliasis was common among children and strongly associated with
      anemia. Anemia should be recognized as an important component of the burden of
      disease from fascioliasis.

PMID- 22403323
TI  - Efficacy of a single oral dose of oxfendazole against Fasciola hepatica in
      naturally infected sheep.
AB  - The efficacy of a single oral dose of 30 mg/kg of oxfendazole against Fasciola
      hepatica was evaluated in a controlled study in naturally infected sheep. Sheep
      were diagnosed by stool microscopy after sedimentation, and positive animals were
      randomized to oxfendazole (N = 20) or no treatment (N = 20). A new stool exam was
      performed 10 days after treatment. All stool microscopies were performed masked
      to the treatment group. No side effects were noticed. All sheep in the control
      group remained infected with similar counts of eggs per gram of stools. None of
      the animals in the treatment group showed Fasciola eggs in stools after 10 days
      of treatment. A single dose of oxfendazole is highly effective against F.
      hepatica, providing a new drug alternative for the control of fascioliasis or
      integrated zoonosis control.

PMID- 22403324
TI  - Drug-drug interaction analysis of pyronaridine/artesunate and ritonavir in
      healthy volunteers.
AB  - A multiple dose, parallel group study was conducted to assess for a drug-drug
      interaction between the pyronaridine/artesunate (PA) combination antimalarial and
      ritonavir. Thirty-four healthy adults were randomized (1:1) to receive PA for 3
      days or PA with ritonavir (100 mg twice daily for 17 days, PA administered on
      Days 8-10). Pharmacokinetic parameters for pyronaridine, artesunate, and its
      active metabolite dihydroartemisinin (DHA) were obtained after the last PA dose
      and for ritonavir on Days 1 and 10. Ritonavir coadministration did not markedly
      change pyronaridine pharmacokinetics but resulted in a 27% increase in artesunate
      area under the curve (AUC) and a 38% decrease in DHA AUC. Ritonavir exposure was
      increased 3.2-fold in the presence of PA. The only relevant safety observations
      were increases in liver enzymes, only reaching a clinically significant grade in
      the PA + ritonavir arm. It was concluded that coadministered ritonavir and PA
      interact to alter exposure to artesunate, DHA, and ritonavir itself.

PMID- 22403325
TI  - Reversible posterior leukoencephalopathy in a venomous snake (Bothrops asper)
      bite victim.
AB  - An 18-year-old man developed posterior reversible leukoencephalopaty after being
      bitten by a venomous snake (Bothrops asper). It is possible that this previously
      unrecognized neurological complication of snake bite envenoming occurred as the
      result of endothelial dysfunction induced by the venom of the offending snake.
      This pathogenetic mechanism has also been implicated as the cause of cerebral
      infarctions in snake bite victims. Alternatively, the leukoencephalopathy might
      have been a complication of antivenom therapy.

PMID- 22403326
TI  - Rethinking indicators of microbial drinking water quality for health studies in
      tropical developing countries: case study in northern coastal Ecuador.
AB  - To address the problem of the health impacts of unsafe drinking water, methods
      are needed to assess microbiologic contamination in water. However, indicators of
      water quality have provided mixed results. We evaluate five assays (three for
      Escherichia coli and one each for enterococci and somatic coliphage) of microbial
      contamination in villages in rural Ecuador that rely mostly on untreated drinking
      water. Only membrane filtration for E. coli using mI agar detected a significant
      association with household diarrheal disease outcome (odds ratio = 1.29, 95%
      confidence interval = 1.02-1.65 in household containers and odds ratio = 1.18,
      95% confidence interval = 1.02-1.37) in source samples. Our analysis and other
      published research points to the need for further consideration of study design
      factors, such as sample size and variability in measurements, when using
      indicator organisms, especially when relating water quality exposure to health
      outcomes. Although indicator organisms are used extensively in health studies, we
      argue that their use requires a full understanding of their purposes and
      limitations.

PMID- 22403327
TI  - Integrated implementation of programs targeting neglected tropical diseases
      through preventive chemotherapy: identifying best practices to roll out programs
      at national scale.
AB  - In 2006 the U.S. Agency for International Development (USAID) established the
      Neglected Tropical Disease (NTD) Control Program to support national governments
      in developing successful, cost-efficient NTD programs that integrate disease
      specific programs into coordinated national initiatives, in accord with the World
      Health Organization recommendations. A 3-stage "roll-out package" has been
      developed for effectively integrating and scaling up such programs to full
      national scale. Stage-1 lays the groundwork-identifying NTD leadership within the
      Ministry of Health, conducting a national Situation Analysis, formulating a
      multiyear Plan of Action, and undertaking a funding gap analysis. Stage-2 focuses
      on scaling up the integrated NTD program-convening national stakeholder meetings,
      developing annual work plans, carrying out disease mapping, and establishing
      monitoring and evaluation activities. Stage-3 aims at ensuring effective
      management-identifying clear roles and responsibilities for partners, and
      creating a central coordinating mechanism. Assessment and reassessment of these
      complex NTD programs that target literally billions of people are essential to
      establish "best practice" strategies for long-term public health success.

PMID- 22403328
TI  - Climate predictors of the spatial distribution of human plague cases in the West
      Nile region of Uganda.
AB  - East Africa has been identified as a region where vector-borne and zoonotic
      diseases are most likely to emerge or re-emerge and where morbidity and mortality
      from these diseases is significant. Understanding when and where humans are most
      likely to be exposed to vector-borne and zoonotic disease agents in this region
      can aid in targeting limited prevention and control resources. Often, spatial and
      temporal distributions of vectors and vector-borne disease agents are predictable
      based on climatic variables. However, because of coarse meteorological
      observation networks, appropriately scaled and accurate climate data are often
      lacking for Africa. Here, we use a recently developed 10-year gridded
      meteorological dataset from the Advanced Weather Research and Forecasting Model
      to identify climatic variables predictive of the spatial distribution of human
      plague cases in the West Nile region of Uganda. Our logistic regression model
      revealed that within high elevation sites (above 1,300 m), plague risk was
      positively associated with rainfall during the months of February, October, and
      November and negatively associated with rainfall during the month of June. These
      findings suggest that areas that receive increased but not continuous rainfall
      provide ecologically conducive conditions for Yersinia pestis transmission in
      this region. This study serves as a foundation for similar modeling efforts of
      other vector-borne and zoonotic disease in regions with sparse observational
      meteorologic networks.

PMID- 22403329
TI  - Accuracy of a commercial IgM ELISA for the diagnosis of human leptospirosis in
      Thailand.
AB  - The Leptospira immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA) has
      been recommended for the rapid diagnosis of leptospirosis in endemic areas. We
      conducted a retrospective case-control study of 218 patients (109 leptospirosis
      cases confirmed by Leptospira culture and/or microscopic agglutination test and
      109 control patients with acute febrile illness) to evaluate the diagnostic
      accuracy of a commercial IgM ELISA (Panbio) in northeast Thailand. Paired serum
      samples taken on admission and at least 10 days after the onset of symptoms were
      tested. Using the cutoff value recommended by the manufacturer (11 Panbio units),
      sensitivity and specificity of IgM ELISA on paired sera were 90.8% and 55.1%. A
      receiver operating characteristic curve was used to determine the optimal cutoff
      value. This was 20 Panbio units, which gave a sensitivity and specificity of
      76.1% and 82.6%, respectively, on paired sera. We conclude that using either
      cutoff value, the accuracy of IgM ELISA is limited in our setting.

PMID- 22403330
TI  - Acoustic characteristics of voiceless bellowing typical of bovine rabies.
AB  - The use of auditory data visualization techniques was useful for distinguishing
      voiceless bellows of a rabid cow from the bellows of estrus-oriented cows,
      because rabid cows created two distinct sounds with a very short silence between
      inhalation and exhalation of the respiratory cycle. The auditory visualization
      techniques as a diagnostic tool may have the potential to serve as a basis for an
      Internet-based application for the early diagnosis of rabies.

PMID- 22403331
TI  - Dengue hemorrhagic fever in Trinidad and Tobago: a case for a conservative
      approach to platelet transfusion.
AB  - Dengue fever is endemic to Trinidad and Tobago. A retrospective analysis of all
      adult admissions at a tertiary hospital in Trinidad treated for dengue during
      January 1-December 31, 2008 was performed. A total of 186 patients were treated
      during this period: 98.9% (184) of the patients were thrombocytopenic; 45.2% were
      severely thrombocytopenic; 13 patients showed development of minor hemorrhage and
      only one case of major hemorrhage; platelet transfusion was given for 7% (13) of
      the cases; and 6 cases for which platelet transfusion was given did not show
      evidence of plasma leakage (12 of these cases did not show evidence of
      hemorrhage). There was a strong association between the lowest platelet value and
      hemoconcentration (chi(2) = 13.16, P < 0.025). No association was found between
      giving a platelet transfusion and hemoconcentration or hemorrhage.
      Thrombocytopenia seen in dengue resolves spontaneously and independent of any
      transfusion used.

PMID- 22403332
TI  - Capillary leakage in travelers with dengue infection: implications for
      pathogenesis.
AB  - Dengue hemorrhagic fever is characterized by the presence of a capillary leak
      syndrome. Its pathogenesis is presumed to differ from that of classical dengue
      fever (DF) and to be associated with secondary dengue infection. Returning
      travelers given a diagnosis of DF were evaluated for capillary leakage with
      abdominal sonography. Data were compared between travelers with primary/secondary
      infection defined by epidemiologic and serologic parameters. A total of 12
      (34.3%) of 35 patients had sonographic signs of capillary leakage. Most (85%)
      patients with capillary leakage had classical DF. Capillary leak was diagnosed in
      32% of primary dengue cases and in 40% of secondary dengue cases (P = 0.69). The
      two patients given a diagnosis of dengue hemorrhagic fever had primary
      infections. The high prevalence of capillary leakage among travelers, most of
      them with primary exposure to dengue, calls into question the importance of
      secondary infection in causing capillary leakage in dengue infection.

PMID- 22403333
TI  - Serosurveillance of eastern equine encephalitis virus in amphibians and reptiles
      from Alabama, USA.
AB  - Eastern equine encephalitis virus (EEEV) is among the most medically important
      arboviruses in North America, and studies suggest a role for amphibians and
      reptiles in its transmission cycle. Serum samples collected from 351 amphibians
      and reptiles (27 species) from Alabama, USA, were tested for the presence of
      antibodies against EEEV. Frogs, turtles, and lizards showed little or no
      seropositivity, and snakes had high seropositivity rates. Most seropositive
      species were preferred or abundant hosts of Culex spp. mosquitoes at Tuskegee
      National Forest, that target ectothermic hosts. The cottonmouth, the most
      abundant ectotherm sampled, displayed a high prevalence of seropositivity,
      indicating its possible role as an amplification and/or over-wintering reservoir
      for EEEV.

PMID- 22403334
TI  - Isolation and characterization of hantaviruses in Far East Russia and etiology of
      hemorrhagic fever with renal syndrome in the region.
AB  - Hemorrhagic fever with renal syndrome (HFRS) is a serious public health issue in
      Far East Russia. Two different hantaviruses were isolated from rodents captured
      in the Khabarovsk region: Amur virus (AMRV; Khekhtsir/AP209/2005 strain from
      Apodemus peninsulae) and Hantaan virus (HTNV; Galkino/AA57/2002 strain from A.
      agrarius). Genetic analysis of the new isolates revealed that the M and L
      segments were apparently different between AMRV and HTNV, but S segments of the
      two viruses were closer. The antigenicities of AMRV, HTNV, and Seoul virus (SEOV)
      were differentiated by cross-neutralization. Serological differential diagnoses
      of 67 HFRS patients in the Prymorsky and Khabarovsk regions of Far East Russia
      were conducted using a neutralization test. The results revealed that the major
      cause of HFRS varied with location in Far East Russia: SEOV for Vladivostok city
      in the Prymorsky region, AMRV in rural areas of the Primorsky region, and
      probably HTNV for the Khabarovsk region.

PMID- 22403335
TI  - Household water treatment in china.

PMID- 22403337
TI  - Significant association between epilepsy and presence of onchocercal nodules:
      case-control study in Cameroon.

PMID- 22403339
TI  - First malaria infections in a cohort of infants in Benin: biological,
      environmental and genetic determinants. Description of the study site, population
      methods and preliminary results.
AB  - OBJECTIVES: Malaria infection of the placenta during pregnancy was found to be
      associated with infant susceptibility to malaria. Other factors such as the
      intensity of malaria transmission and the nutritional status of the child might
      also play a role, which has not been adequately taken into account in previous
      studies. The aim of this study was to assess precisely the parts played by
      environmental, nutritional and biological determinants in first malaria
      infections, with a special interest in the role of placental infection. The
      objective of this paper is not to present final results but to outline the
      rationale of the study, to describe the methods used and to report baseline data.
      DESIGN: A cohort of infants followed with a parasitological (symptomatic and
      asymptomatic parasitaemia) and nutritional follow-up from birth to 18 months.
      Ecological, entomological and behavioural data were collected along the duration
      of the study. SETTING: A rural area in Benin with two seasonal peaks in malaria
      transmission. PARTICIPANTS: 656 infants of women willing to participate in the
      study, giving birth in one of the three maternity clinics and living in one of
      the nine villages of the study area. PRIMARY OUTCOME MEASURES: The time and
      frequency of first malaria parasitaemias in infants, according to Plasmodium
      falciparum infection of the placenta. RESULTS: 11% of mothers had a malaria
      infected placenta at delivery. Mosquito catches made every 6 weeks in the area
      showed an average annual P falciparum entomological inoculation rate of 15.5,
      with important time and space variations depending on villages. Similarly, the
      distribution of rainfalls, maximal during the two rainy seasons, was
      heterogeneous over the area. CONCLUSIONS: Considering the multidisciplinary
      approach of all factors potentially influencing the malaria status of newborn
      babies, this study should bring evidence on the implication of placental malaria
      in the occurrence of first malaria infections in infants.

PMID- 22403340
TI  - A survey of early health effects of the Eyjafjallajokull 2010 eruption in
      Iceland: a population-based study.
AB  - OBJECTIVE: To estimate physical and mental health effects of the Eyjafjallajokull
      volcanic eruption on nearby residents. DESIGN: Cross-sectional study. SETTING:
      The Icelandic volcano Eyjafjallajokull erupted on 14 April 2010. The eruption
      lasted for about 6 weeks and was explosive, ejecting some 8 million tons of fine
      particles into the atmosphere. Due to prevailing winds, the ash spread mostly to
      the south and south-east, first over the rural region to the south, later over
      the Atlantic Ocean and Europe, closing European air space for several days.
      PARTICIPANTS: Residents (n=207) of the most ash-exposed rural area south and east
      of the volcano. METHODS: The study period was from 31 May to 11 June 2010.
      Participants were examined by a physician. To ascertain respiratory health,
      standardised spirometry was performed before and after the use of a
      bronchodilator. All adult participants answered questionnaires about mental and
      physical health, their children's health and the use of protective equipment.
      RESULTS: Every other adult participant reported irritation in eyes and upper
      airway when exposed to volcanic ash. Adults (n=26) and children (n=5) with pre
      existing asthma frequently reported worsening of their symptoms. No serious
      health problems requiring hospitalisation could be attributed to the eruption.
      The majority of the participants reported no abnormal physical or mental symptoms
      to the examining physician. Compared to an age- and gender-matched reference
      group, the ash-exposed participants reported lower smoking rates and were less
      likely to have ventilation impairment. Less than 10% of the participants reported
      symptoms of stress, anxiety or depression. CONCLUSIONS: Short-term ash exposure
      was associated with upper airway irritation symptoms and exacerbation of pre
      existing asthma but did not contribute to serious health problems. The exposure
      did not impair respiratory function compared to controls. Outdoor use of
      protective glasses and face masks was considered protective against irritation in
      eyes and upper airway.

PMID- 22403341
TI  - Will more restrictive indications decrease rates of urinary catheterisation? An
      historical comparative study.
AB  - OBJECTIVES: To determine if more restrictive indications for urinary
      catheterisation reinforced by daily chart review will lower catheterisation
      rates. DESIGN: An historical comparative observational study. SETTING: An
      internal medicine department in a regional hospital in Israel. PARTICIPANTS: The
      authors compared 882 patients hospitalised after a change in policy to an
      historical cohort of 690 hospitalised patients. Exclusions included patients less
      than age 30 and those with bladder outlet obstruction. INTERVENTION: Emergency
      and internal medicine department physicians received instruction on a more
      restricted urinary catheterisation policy. During daily chart rounds, admissions
      were discussed with an emphasis on the appropriateness of all new urinary
      catheter insertions. MAIN OUTCOME MEASURES: The primary outcome measure was
      catheterisation rate by admission diagnosis. Secondary outcome measures were the
      need for post-admission in hospital catheterisations and the rate of indwelling
      catheters 14 or more days after discharge. RESULTS: There was a reduction in
      catheterisation rate in patients with congestive heart failure from 30/106
      (29.3%) to 3/107 (2.8%) (p<0.001), in patients with an admission diagnosis of
      fever unable to provide a urine sample for culture from 35/132 (26.5%) to 12/153
      (7.8%) (p<0.001) and in patients admitted for palliative care from 51.7% (15/29)
      to 12.0% (3/25) (p=0.002). The overall rate of catheterisation decreased from
      17.5% (121/690) to 6.6% (58/882) (p<0.001). There was only one indicated
      catheterisation after admission due to the change in policy, and the proportion
      of patients discharged with catheters decreased. CONCLUSION: The use of more
      restrictive indications for urinary catheterisation along with daily chart rounds
      can reduce the rate of urinary catheterisation in an internal medicine department
      without adverse consequences.

PMID- 22403342
TI  - Physical exercise in southern Germany: a cross-sectional study of an urban
      population.
AB  - OBJECTIVES: The aim of this study was to investigate the degree of physical
      exercise and self-assessment of physical fitness (PF) and their relationship to
      health- and behaviour-specific factors in a randomly selected sample of an urban
      population in southern Germany. DESIGN: Cross-sectional study. SETTING: In the
      southern German city of Leutkirch. PARTICIPANTS: 2187 subjects randomly selected
      from the registry of inhabitants. Of the selected group, aged 18-65 years, 52.1%
      were women and 47.9% men. PRIMARY AND SECONDARY OUTCOME MEASURES: Participants
      were asked how many hours per week they spent on physical exercise and sports.
      They were also asked to rate their own performance and/or PF. RESULTS: Overall,
      38.9% of the participants reported no physical exercise. Men reported a higher
      level of physical exercise than did women. Less exercise was reported by subjects
      with diabetes, high body mass index and waist-to-hip ratio and by those who were
      underweight. Alcohol consumption, smoker status and higher educational level
      showed a positive association with physical exercise. A negative trend with
      respect to moderate physical exercise was observed for those with metabolic
      syndrome, diabetes, hypertension and hepatic steatosis, but this was
      statistically significant only for subjects with diabetes. In both men and women,
      there was a relationship between self-assessed 'good' PF and high physical
      exercise. CONCLUSIONS: The data show that a large proportion of the study
      population is not physically active; specific risk groups (overweight subjects,
      older subjects, smokers or subjects with low educational level) are even less
      active. The data suggest that there is a great potential for measures promoting
      physical exercise in these groups.

PMID- 22403343
TI  - Familial factors and child characteristics as predictors of injuries in toddlers:
      a prospective cohort study.
AB  - OBJECTIVE: To identify family and child characteristics that put toddlers at risk
      of injuries. DESIGN: A prospective cohort study. SETTING: This study was based on
      the Norwegian Mother and Child Cohort Study, conducted by the Norwegian Institute
      of Public Health. PARTICIPANTS: The study sample consisted of 26 087 children and
      their mothers. OUTCOME MEASURES: Family and child characteristics measured before
      or at 18 months of age were investigated as potential predictors of hospital
      attended injuries that occurred between 18 and 36 months of age. RESULTS: In the
      multivariable analysis, younger maternal age (OR 0.93, 95% CI 0.86 to 1.00),
      financial problems (OR 1.18, 95% CI 1.01 to 1.39), maternal mental distress (OR
      1.09, 95% CI 1.03 to 1.16), having older siblings (OR 1.22, 95% CI 1.08 to 1.39),
      increased gestational age at birth (OR 1.04, 95% CI 1.00 to 1.07) and male gender
      (OR 1.26, 95% CI 1.11 to 1.42) were risk factors for hospital-attended injuries.
      Children with impaired gross motor development had a decreased risk of injury (OR
      0.65, 95% CI 0.42 to 0.99), whereas those with impaired fine motor development
      had an increased risk (OR 1.55, 95% CI 1.22 to 1.97). Shyness was a protective
      factor (OR 0.92, 95% CI 0.86 to 0.98). Children with three reported attention
      problems had a slightly increased risk of hospital-attended injuries (OR 1.33,
      95% CI 1.02 to 1.72; p=0.035); otherwise, behaviour was not a significant risk
      factor. CONCLUSIONS: This study demonstrated that a wide variety of factors were
      in play as predictors of injuries in young children. Both child-related factors
      (gender, gestational age at birth, child motor development, shyness and
      attention) and familial factors (having older siblings, maternal age, financial
      difficulties and maternal mental health problems) were associated with injuries
      in toddlers.

PMID- 22403344
TI  - Circulating miR-15b and miR-130b in serum as potential markers for detecting
      hepatocellular carcinoma: a retrospective cohort study.
AB  - OBJECTIVE: Serum alpha-fetoprotein (AFP) is the most commonly used biomarker for
      screening hepatocellular carcinoma (HCC) but fails to detect about half of the
      patients. Thus, we investigated if circulating microRNAs (miRNAs) could
      outperform AFP for HCC detection. DESIGN: A retrospective cohort study. SETTING:
      Two clinical centres in China. PARTICIPANTS: The exploration phase included 96
      patients with HCC who received primary curative hepatectomy, and the validation
      phase included 29 hepatitis B carriers, 57 patients with HCC and 30 healthy
      controls. MAIN OUTCOME MEASURES: Expression of miRNAs was measured by real-time
      quantitative reverse transcription-PCR. Areas under receiver operating
      characteristic curves were used to determine the feasibility of using serum miRNA
      concentration as a diagnostic marker for defining HCC. A multivariate logistic
      regression analysis was used to evaluate performances of combined serum miRNAs.
      RESULTS: In the exploration phase, miRNA profiling on resected tumour/adjacent
      non-tumour tissues identified miR-15b, miR-21, miR-130b and miR-183 highly
      expressed in tumours. These miRNAs were also detectable in culture supernatants
      of HCC cell lines and in serum samples of patients. Remarkably, these serum
      miRNAs were markedly reduced after surgery, indicating the tumour-derived source
      of these circulating miRNAs. In a cross-centre validation study, combined miR-15b
      and miR-130b demonstrated as a classifier for HCC detection, yielding a receiver
      operating characteristic curve area of 0.98 (98.2% sensitivity and 91.5%
      specificity). The detection sensitivity of the classifier in a subgroup of HCCs
      with low AFP (<20 ng/ml) was 96.7%. The classifier also identified early-stage
      HCC cases that could not be detected by AFP. CONCLUSION: The combined miR-15b and
      miR-130b classifier is a serum biomarker with clinical value for HCC screening.

PMID- 22403345
TI  - Intermittent hypoxia conditioning protects mitochondrial cytochrome c oxidase of
      rat cerebellum from ethanol withdrawal stress.
AB  - Intermittent hypoxia (IH) conditioning minimizes neurocognitive impairment and
      stabilizes brain mitochondrial integrity during ethanol withdrawal (EW) in rats,
      but the mitoprotective mechanism is unclear. We investigated whether IH
      conditioning protects a key mitochondrial enzyme, cytochrome c oxidase (COX),
      from EW stress by inhibiting mitochondrially directed apoptotic pathways
      involving cytochrome c, Bax, or phosphor-P38 (pP38). Male rats completed two
      cycles of a 4-wk ethanol diet (6.5%) and 3 wk of EW. An IH program consisting of
      5-10 bouts of 5-8 min of mild hypoxia (9.5-10% inspired O(2)) and 4 min of
      reoxygenation for 20 consecutive days began 3 days before the first EW period.
      For some animals, vitamin E replaced IH conditioning to test the contributions of
      antioxidant mechanisms to IH's mitoprotection. During the second EW, cerebellar
      related motor function was evaluated by measuring latency of fall from a rotating
      rod (Rotarod test). After the second EW, COX activity in cerebellar mitochondria
      was measured by spectrophotometry, and COX, cytochrome c, Bax, and pP38 content
      were analyzed by immunoblot. Mitochondrial protein oxidation was detected by
      measuring carbonyl contents and by immunochemistry. Earlier IH conditioning
      prevented motor impairment, COX inactivation, depletion of COX subunit 4, protein
      carbonylation, and P38 phosphorylation during EW. IH did not prevent cytochrome c
      depletion during EW, and Bax content was unaffected by EW +/- IH. Vitamin E
      treatment recapitulated IH protection of COX, and P38 inhibition attenuated
      protein oxidation during EW. Thus IH protects COX and improves cerebellar
      function during EW by limiting P38-dependent oxidative damage.

PMID- 22403346
TI  - Severe acute intermittent hypoxia elicits phrenic long-term facilitation by a
      novel adenosine-dependent mechanism.
AB  - Acute intermittent hypoxia [AIH; 3, 5-min episodes; 35-45 mmHg arterial PO(2)
      (Pa(O(2)))] elicits serotonin-dependent phrenic long-term facilitation (pLTF), a
      form of phrenic motor facilitation (pMF) initiated by G(q) protein-coupled
      metabotropic 5-HT(2) receptors. An alternate pathway to pMF is induced by G(s)
      protein-coupled metabotropic receptors, including adenosine A(2A) receptors. AIH
      induced pLTF is dominated by the serotonin-dependent pathway and is actually
      restrained via inhibition from the adenosine-dependent pathway. Here, we
      hypothesized that severe AIH shifts pLTF from a serotonin-dependent to an
      adenosine-dependent form of pMF. pLTF induced by severe (25-30 mmHg Pa(O(2))) and
      moderate (45-55 mmHg Pa(O(2))) AIH were compared in anesthetized rats, with and
      without intrathecal (C4) spinal A(2A) (MSX-3, 130 ng/kg, 12 MUl) or 5-HT receptor
      antagonist (methysergide, 300 MUg/kg, 15 MUl) injections. During severe, but not
      moderate AIH, progressive augmentation of the phrenic response during hypoxic
      episodes was observed. Severe AIH (78% +/- 8% 90 min post-AIH, n = 6) elicited
      greater pLTF vs. moderate AIH (41% +/- 12%, n = 8; P < 0.05). MSX-3 (28% +/- 6%;
      n = 6; P < 0.05) attenuated pLTF following severe AIH, but enhanced pLTF
      following moderate AIH (86% +/- 26%; n = 8; P < 0.05). Methysergide abolished
      pLTF after moderate AIH (12% +/- 5%; n = 6; P = 0.035), but had no effect after
      severe AIH (66 +/- 13%; n = 5; P > 0.05). Thus severe AIH shifts pLTF from a
      serotonin-dependent to an adenosine-dependent mechanism; the adenosinergic
      pathway inhibits the serotonergic pathway following moderate AIH. Here we
      demonstrate a novel adenosine-dependent pathway to pLTF following severe AIH.
      Shifts in the mechanisms of respiratory plasticity provide the ventilatory
      control system greater flexibility as challenges that differ in severity are
      confronted.

PMID- 22403347
TI  - Brachial artery adaptation to lower limb exercise training: role of shear stress.
AB  - Lower limb exercise increases upper limb conduit artery blood flow and shear
      stress, and leg exercise training can enhance upper limb vascular function. We
      therefore examined the contribution of shear stress to changes in vascular
      function in the nonexercising upper limbs in response to lower limb cycling
      exercise training. Initially, five male subjects underwent bilateral brachial
      artery duplex ultrasound to measure blood flow and shear responses to 30-min
      cycling exercise at 80% of maximal heart rate. Responses in one forearm were
      significantly (P < 0.05) attenuated via cuff inflation throughout the exercise
      bout. An additional 11 subjects participated in an 8-wk cycle training study
      undertaken at a similar intensity, with unilateral cuff inflation around the
      forearm during each exercise bout. Bilateral brachial artery flow-mediated
      dilation responses to a 5-min ischemic stimulus (FMD%), an ischemic handgrip
      exercise stimulus (iEX), and endothelium-independent NO donor administration
      [glyceryl trinitrate (GTN)] were measured at 2, 4, and 8 wk. Cycle training
      increased FMD% in the noncuffed limb at week 2, after which time responses
      returned toward baseline levels (5.8 +/- 4.1, 8.6 +/- 3.8, 7.4 +/- 3.5, 6.0 +/-
      2.3 at 0, 2, 4 and 8 wk, respectively; ANOVA: P = 0.04). No changes in FMD% were
      observed in the cuffed arm. No changes were evident in response to iEX or GTN in
      either the cuffed or noncuffed arms (P > 0.05) across the 8-wk intervention
      period. Our data suggest that lower limb cycle training induces a transient
      increase in upper limb vascular function in healthy young humans, which is, at
      least partly, mediated via shear stress.

PMID- 22403348
TI  - Metabolic and cardiac signaling effects of inhaled hydrogen sulfide and low
      oxygen in male rats.
AB  - Low concentrations of inhaled hydrogen sulfide (H(2)S) induce hypometabolism in
      mice. Biological effects of H(2)S in in vitro systems are augmented by lowering
      O(2) tension. Based on this, we hypothesized that reduced O(2) tension would
      increase H(2)S-mediated hypometabolism in vivo. To test this, male Sprague-Dawley
      rats were exposed to 80 ppm H(2)S at 21% O(2) or 10.5% O(2) for 6 h followed by 1
      h recovery at room air. Rats exposed to H(2)S in 10.5% O(2) had significantly
      decreased body temperature and respiration compared with preexposure levels.
      Heart rate was decreased by H(2)S administered under both O(2) levels and did not
      return to preexposure levels after 1 h recovery. Inhaled H(2)S caused epithelial
      exfoliation in the lungs and increased plasma creatine kinase-MB activity. The
      effect of inhaled H(2)S on prosurvival signaling was also measured in heart and
      liver. H(2)S in 21% O(2) increased Akt-P(Ser473) and GSK-3beta-P(Ser9) in the
      heart whereas phosphorylation was decreased by H(2)S in 10.5% O(2), indicating
      O(2) dependence in regulating cardiac signaling pathways. Inhaled H(2)S and low
      O(2) had no effect on liver Akt. In summary, we found that lower O(2) was needed
      for H(2)S-dependent hypometabolism in rats compared with previous findings in
      mice. This highlights the possibility of species differences in physiological
      responses to H(2)S. Inhaled H(2)S exposure also caused tissue injury to the lung
      and heart, which raises concerns about the therapeutic safety of inhaled H(2)S.
      In conclusion, these findings demonstrate the importance of O(2) in influencing
      physiological and signaling effects of H(2)S in mammalian systems.

PMID- 22403349
TI  - Adaptation of swallowing hyo-laryngeal kinematics is distinct in oral vs.
      pharyngeal sensory processing.
AB  - Before a bolus is pushed into the pharynx, oral sensory processing is critical
      for planning movements of the subsequent pharyngeal swallow, including hyoid bone
      and laryngeal (hyo-laryngeal) kinematics. However, oral and pharyngeal sensory
      processing for hyo-laryngeal kinematics is not fully understood. In 11 healthy
      adults, we examined changes in kinematics with sensory adaptation, sensitivity
      shifting, with oropharyngeal swallows vs. pharyngeal swallows (no oral
      processing), and with various bolus volumes and tastes. Only pharyngeal swallows
      showed sensory adaptation (gradual changes in kinematics with repeated exposure
      to the same bolus). Conversely, only oropharyngeal swallows distinguished volume
      differences, whereas pharyngeal swallows did not. No taste effects were observed
      for either swallow type. The hyo-laryngeal kinematics were very similar between
      oropharyngeal swallows and pharyngeal swallows with a comparable bolus.
      Sensitivity shifting (changing sensory threshold for a small bolus when it
      immediately follows several very large boluses) was not observed in pharyngeal or
      oropharyngeal swallowing. These findings indicate that once oral sensory
      processing has set a motor program for a specific kind of bolus (i.e., 5 ml
      water), hyo-laryngeal movements are already highly standardized and optimized,
      showing no shifting or adaptation regardless of repeated exposure (sensory
      adaptation) or previous sensory experiences (sensitivity shifting). Also, the
      oral cavity is highly specialized for differentiating certain properties of a
      bolus (volume) that might require a specific motor plan to ensure swallowing
      safety, whereas the pharyngeal cavity does not make the same distinctions.
      Pharyngeal sensory processing might not be able to adjust motor plans created by
      the oral cavity once the swallow has already been triggered.

PMID- 22403350
TI  - Postnatal development and activation of L-type Ca2+ currents in locus ceruleus
      neurons: implications for a role for Ca2+ in central chemosensitivity.
AB  - Little is known about the role of Ca(2+) in central chemosensitive signaling. We
      use electrophysiology to examine the chemosensitive responses of tetrodotoxin
      (TTX)-insensitive oscillations and spikes in neurons of the locus ceruleus (LC),
      a chemosensitive region involved in respiratory control. We show that both TTX
      insensitive spikes and oscillations in LC neurons are sensitive to L-type Ca(2+)
      channel inhibition and are activated by increased CO(2)/H(+). Spikes appear to
      arise from L-type Ca(2+) channels on the soma whereas oscillations arise from L
      type Ca(2+) channels that are distal to the soma. In HEPES-buffered solution
      (nominal absence of CO(2)/HCO(3)(-)), acidification does not activate either
      oscillations or spikes. When CO(2) is increased while extracellular pH is held
      constant by elevated HCO(3)(-), both oscillation and spike frequency increase.
      Furthermore, plots of both oscillation and spike frequency vs. intracellular
      [HCO(3)(-)]show a strong linear correlation. Increased frequency of TTX
      insensitive spikes is associated with increases in intracellular Ca(2+)
      concentrations. Finally, both the appearance and frequency of TTX-insensitive
      spikes and oscillations increase over postnatal ages day 3-16. Our data suggest
      that 1) L-type Ca(2+) currents in LC neurons arise from channel populations that
      reside in different regions of the neuron, 2) these L-type Ca(2+) currents
      undergo significant postnatal development, and 3) the activity of these L-type
      Ca(2+) currents is activated by increased CO(2) through a HCO(3)(-)-dependent
      mechanism. Thus the activity of L-type Ca(2+) channels is likely to play a role
      in the chemosensitive response of LC neurons and may underlie significant changes
      in LC neuron chemosensitivity during neonatal development.

PMID- 22403351
TI  - Sex differences in hemodynamic and sympathetic neural firing patterns during
      orthostatic challenge in humans.
AB  - Recent evidence suggests that young men and women may have different strategies
      for regulating arterial blood pressure, and the purpose of the present study was
      to determine if sex differences exist in diastolic arterial pressure (DAP) and
      muscle sympathetic nerve activity (MSNA) relations during simulated orthostatic
      stress. We hypothesized that young men would demonstrate stronger DAP-MSNA
      coherence and a greater percentage of "consecutive integrated bursts" during
      orthostatic stress. Fourteen men and 14 women (age 23 +/- 1 yr) were examined at
      rest and during progressive lower body negative pressure (LBNP; -5 to -40 mmHg).
      Progressive LBNP did not alter mean arterial pressure (MAP) in either sex. Heart
      rate increased and stroke volume decreased to a greater extent during LBNP in
      women (interactions, P < 0.05). DAP-MSNA coherence was strong (i.e., r >= 0.5) at
      rest and increased throughout all LBNP stages in men. In contrast, DAP-MSNA
      coherence was lower in women, and responses to progressive LBNP were attenuated
      compared with men (time * sex, P = 0.029). Men demonstrated a higher percentage
      of consecutive bursts during all stages of LBNP (sex, P < 0.05), although the
      percentage of consecutive bursts increased similarly during progressive LBNP
      between sexes. In conclusion, men and women demonstrate different firing patterns
      of integrated MSNA during LBNP that appear to be related to differences in DAP
      oscillatory patterns. Men tend to have more consecutive bursts, which likely
      contribute to a stronger DAP-MSNA coherence. These findings may help explain why
      young women are more prone to orthostatic intolerance.

PMID- 22403353
TI  - Worldwide lessons from 11 March.

PMID- 22403352
TI  - Pulsatile flow during cardiopulmonary bypass preserves postoperative
      microcirculatory perfusion irrespective of systemic hemodynamics.
AB  - The onset of nonpulsatile cardiopulmonary bypass is known to deteriorate
      microcirculatory perfusion, but it has never been investigated whether this may
      be prevented by restoration of pulsatility during extracorporeal circulation. We
      therefore investigated the distinct effects of nonpulsatile and pulsatile flow on
      microcirculatory perfusion during on-pump cardiac surgery. Patients undergoing
      coronary artery bypass graft surgery were randomized into a nonpulsatile (n = 17)
      or pulsatile (n = 16) cardiopulmonary bypass group. Sublingual mucosal
      microvascular perfusion was measured at distinct perioperative time intervals
      using sidestream dark field imaging, and quantified as the level of perfused
      small vessel density and microvascular flow index (vessel diameter < 20 MUm).
      Microcirculation measurements were paralleled by hemodynamic and free hemoglobin
      analyses. The pulse wave during pulsatile bypass estimated 58 +/- 17% of the
      baseline blood pressure waveform. The observed reduction in perfused vessel
      density during aorta cross-clamping was only restored in the pulsatile flow group
      and increased from 15.5 +/- 2.4 to 20.3 +/- 3.7 mm/mm(2) upon intensive care
      admission (P < 0.01). The median postoperative microvascular flow index was
      higher in the pulsatile group [2.6 (2.5-2.9)] than in the nonpulsatile group [2.1
      (1.7-2.5); P = 0.001]. Pulsatile flow was not associated with augmentation of
      free hemoglobin production and was paralleled by improved oxygen consumption from
      70 +/- 14 to 82 +/- 16 ml.min(-1).m(-2) (P = 0.01) at the end of aortic cross
      clamping. In conclusion, pulsatile cardiopulmonary bypass preserves
      microcirculatory perfusion throughout the early postoperative period,
      irrespective of systemic hemodynamics. This observation is paralleled by an
      increase in oxygen consumption during pulsatile flow, which may hint toward
      decreased microcirculatory heterogeneity during extracorporeal circulation and
      preservation of microcirculatory perfusion throughout the perioperative period.

PMID- 22403358
TI  - Avian influenza. Surprising twist in debate over lab-made H5N1.

PMID- 22403359
TI  - Research spending. A bumper year for Chinese science.

PMID- 22403360
TI  - Scientific misconduct. Reviewer's deja vu, French science sleuthing uncover
      plagiarized papers.

PMID- 22403361
TI  - Energy research. Report on future of fusion research says U.S. should hedge its
      bets.

PMID- 22403362
TI  - Particle physics. Last hurrah: final Tevatron data show hints of Higgs boson.

PMID- 22403363
TI  - Marine biology. Light in the deep.

PMID- 22403364
TI  - Marine biology. Extraordinary eyes.

PMID- 22403365
TI  - Japan disaster. One year after the devastation, Tohoku designs its renewal.

PMID- 22403366
TI  - Japan disaster. Radioactive limbo.

PMID- 22403368
TI  - Science funding. The next big(ger) thing.

PMID- 22403367
TI  - Japan disaster. Nuclear ambivalence no more?

PMID- 22403369
TI  - Asian medicine: exploitation of wildlife.

PMID- 22403370
TI  - Asian medicine: exploitation of plants.

PMID- 22403371
TI  - Business journals combat coercive citation.

PMID- 22403372
TI  - Chimp research policy: think global.

PMID- 22403373
TI  - Comment on "Fossilized nuclei and germination structures identify Ediacaran
      'animal embryos' as encysting protists".
AB  - On the basis of putative nuclei and endospores, Huldtgren et al. (Reports, 23
      December 2011, p. 1696) propose that embryo-like Doushantuo microfossils are
      nonmetazoan holozoans akin to mesomycetozoeans. However, both size and
      preservation preclude interpretation of internal structures as nuclei. Moreover,
      the authors may have conflated two different populations; some specimens display
      a pseudoparenchymatous organization incompatible with a mesomycetozoean
      comparison.

PMID- 22403375
TI  - Neuroscience. Youth culture in the adult brain.

PMID- 22403376
TI  - Geochemistry. Moonstruck magnetism.

PMID- 22403377
TI  - Social science. Experimenting with politics.

PMID- 22403378
TI  - Materials science. Swell approaches for changing polymer shapes.

PMID- 22403379
TI  - Ecology. The human factor.

PMID- 22403380
TI  - Cell biology. Embryonic clutch control.

PMID- 22403381
TI  - Retrospective. Roy J. Britten (1919-2012).

PMID- 22403382
TI  - Nuclear fuel in a reactor accident.
AB  - Nuclear accidents that lead to melting of a reactor core create heterogeneous
      materials containing hundreds of radionuclides, many with short half-lives. The
      long-lived fission products and transuranium elements within damaged fuel remain
      a concern for millennia. Currently, accurate fundamental models for the
      prediction of release rates of radionuclides from fuel, especially in contact
      with water, after an accident remain limited. Relatively little is known about
      fuel corrosion and radionuclide release under the extreme chemical, radiation,
      and thermal conditions during and subsequent to a nuclear accident. We review the
      current understanding of nuclear fuel interactions with the environment,
      including studies over the relatively narrow range of geochemical, hydrological,
      and radiation environments relevant to geological repository performance, and
      discuss priorities for research needed to develop future predictive models.

PMID- 22403383
TI  - Natural SIV hosts: showing AIDS the door.
AB  - Many species of African nonhuman primates are naturally infected with simian
      immunodeficiency viruses (SIVs) in the wild and in captivity. In contrast to HIV
      infected humans, these natural SIV hosts typically do not develop AIDS, despite
      chronic infection with a highly replicating virus. In this Review, we discuss the
      most recent advances on the mechanisms of protection from disease progression in
      natural SIV hosts, with emphasis on how they differ from pathogenic HIV/SIV
      infections of humans and rhesus macaques. These mechanisms include: (i)
      resolution of immune activation after acute infection, (ii) restricted pattern of
      target cell infection, and (iii) protection from mother-to-infant transmission.
      We highlight the areas that should be pursued in future studies, focusing on
      potential applications for the treatment and prevention of HIV infection.

PMID- 22403384
TI  - Fluorescence imaging of cellular metabolites with RNA.
AB  - Genetically encoded sensors are powerful tools for imaging intracellular
      metabolites and signaling molecules. However, developing sensors is challenging
      because they require proteins that undergo conformational changes upon binding
      the desired target molecule. We describe an approach for generating fluorescent
      sensors based on Spinach, an RNA sequence that binds and activates the
      fluorescence of a small-molecule fluorophore. We show that these sensors can
      detect a variety of different small molecules in vitro and in living cells. These
      RNAs constitute a versatile approach for fluorescence imaging of small molecules
      and have the potential to detect essentially any cellular biomolecule.

PMID- 22403385
TI  - Designing responsive buckled surfaces by halftone gel lithography.
AB  - Self-actuating materials capable of transforming between three-dimensional shapes
      have applications in areas as diverse as biomedicine, robotics, and tunable micro
      optics. We introduce a method of photopatterning polymer films that yields
      temperature-responsive gel sheets that can transform between a flat state and a
      prescribed three-dimensional shape. Our approach is based on poly(N
      isopropylacrylamide) copolymers containing pendent benzophenone units that allow
      cross-linking to be tuned by irradiation dose. We describe a simple method of
      halftone gel lithography using only two photomasks, wherein highly cross-linked
      dots embedded in a lightly cross-linked matrix provide access to nearly
      continuous, and fully two-dimensional, patterns of swelling. This method is used
      to fabricate surfaces with constant Gaussian curvature (spherical caps, saddles,
      and cones) or zero mean curvature (Enneper's surfaces), as well as more complex
      and nearly closed shapes.

PMID- 22403386
TI  - Coking- and sintering-resistant palladium catalysts achieved through atomic layer
      deposition.
AB  - We showed that alumina (Al(2)O(3)) overcoating of supported metal nanoparticles
      (NPs) effectively reduced deactivation by coking and sintering in high
      temperature applications of heterogeneous catalysts. We overcoated palladium NPs
      with 45 layers of alumina through an atomic layer deposition (ALD) process that
      alternated exposures of the catalysts to trimethylaluminum and water at 200
      degrees C. When these catalysts were used for 1 hour in oxidative dehydrogenation
      of ethane to ethylene at 650 degrees C, they were found by thermogravimetric
      analysis to contain less than 6% of the coke formed on the uncoated catalysts.
      Scanning transmission electron microscopy showed no visible morphology changes
      after reaction at 675 degrees C for 28 hours. The yield of ethylene was improved
      on all ALD Al(2)O(3) overcoated Pd catalysts.

PMID- 22403387
TI  - Isolated metal atom geometries as a strategy for selective heterogeneous
      hydrogenations.
AB  - Facile dissociation of reactants and weak binding of intermediates are key
      requirements for efficient and selective catalysis. However, these two variables
      are intimately linked in a way that does not generally allow the optimization of
      both properties simultaneously. By using desorption measurements in combination
      with high-resolution scanning tunneling microscopy, we show that individual,
      isolated Pd atoms in a Cu surface substantially lower the energy barrier to both
      hydrogen uptake on and subsequent desorption from the Cu metal surface. This
      facile hydrogen dissociation at Pd atom sites and weak binding to Cu allow for
      very selective hydrogenation of styrene and acetylene as compared with pure Cu or
      Pd metal alone.

PMID- 22403388
TI  - An impactor origin for lunar magnetic anomalies.
AB  - The Moon possesses strong magnetic anomalies that are enigmatic given the weak
      magnetism of lunar rocks. We show that the most prominent grouping of anomalies
      can be explained by highly magnetic extralunar materials from the projectile that
      formed the largest and oldest impact crater on the Moon: the South Pole-Aitken
      basin. The distribution of projectile materials from a model oblique impact
      coincides with the distribution of magnetic anomalies surrounding this basin, and
      the magnetic properties of these materials can account for the intensity of the
      observed anomalies if they were magnetized in a core dynamo field. Distal ejecta
      from this event can explain the origin of isolated magnetic anomalies far from
      this basin.

PMID- 22403389
TI  - Reconstruction of Microraptor and the evolution of iridescent plumage.
AB  - Iridescent feather colors involved in displays of many extant birds are produced
      by nanoscale arrays of melanin-containing organelles (melanosomes). Data relevant
      to the evolution of these colors and the properties of melanosomes involved in
      their generation have been limited. A data set sampling variables of extant avian
      melanosomes reveals that those forming most iridescent arrays are distinctly
      narrow. Quantitative comparison of these data with melanosome imprints densely
      sampled from a previously unknown specimen of the Early Cretaceous feathered
      Microraptor predicts that its plumage was predominantly iridescent. The capacity
      for simple iridescent arrays is thus minimally inferred in paravian dinosaurs.
      This finding and estimation of Microraptor feathering consistent with an
      ornamental function for the tail suggest a centrality for signaling in early
      evolution of plumage and feather color.

PMID- 22403390
TI  - Molecular determinants of scouting behavior in honey bees.
AB  - Little is known about the molecular basis of differences in behavior among
      individuals. Here we report consistent novelty-seeking behavior, across different
      contexts, among honey bees in their tendency to scout for food sources and nest
      sites, and we reveal some of the molecular underpinnings of this behavior
      relative to foragers that do not scout. Food scouts showed extensive differences
      in brain gene expression relative to other foragers, including differences
      related to catecholamine, glutamate, and gamma-aminobutyric acid signaling.
      Octopamine and glutamate treatments increased the likelihood of scouting, whereas
      dopamine antagonist treatment decreased it. These findings demonstrate intriguing
      similarities in human and insect novelty seeking and suggest that this trait,
      which presumably evolved independently in these two lineages, may be subserved by
      conserved molecular components.

PMID- 22403393
TI  - Bouffee delirante and contemporary psychiatric nosology.

PMID- 22403392
TI  - Nucleosomes suppress spontaneous mutations base-specifically in eukaryotes.
AB  - It is unknown how the composition and structure of DNA within the cell affect
      spontaneous mutations. Theory suggests that in eukaryotic genomes, nucleosomal
      DNA undergoes fewer C->T mutations because of suppressed cytosine hydrolytic
      deamination relative to nucleosome-depleted DNA. Comparative genomic analyses and
      a mutation accumulation experiment showed that nucleosome occupancy nearly
      eliminated cytosine deamination, resulting in an ~50% decrease of the C->T
      mutation rate in nucleosomal DNA. Furthermore, the rates of G->T and A->T
      mutations were also about twofold suppressed by nucleosomes. On the basis of
      these results, we conclude that nucleosome-dependent mutation spectra affect
      eukaryotic genome structure and evolution and may have implications for
      understanding the origin of mutations in cancers and in induced pluripotent stem
      cells.

PMID- 22403391
TI  - Atomic view of a toxic amyloid small oligomer.
AB  - Amyloid diseases, including Alzheimer's, Parkinson's, and the prion conditions,
      are each associated with a particular protein in fibrillar form. These amyloid
      fibrils were long suspected to be the disease agents, but evidence suggests that
      smaller, often transient and polymorphic oligomers are the toxic entities. Here,
      we identify a segment of the amyloid-forming protein alphaB crystallin, which
      forms an oligomeric complex exhibiting properties of other amyloid oligomers:
      beta-sheet-rich structure, cytotoxicity, and recognition by an oligomer-specific
      antibody. The x-ray-derived atomic structure of the oligomer reveals a
      cylindrical barrel, formed from six antiparallel protein strands, that we term a
      cylindrin. The cylindrin structure is compatible with a sequence segment from the
      beta-amyloid protein of Alzheimer's disease. Cylindrins offer models for the
      hitherto elusive structures of amyloid oligomers.

PMID- 22403394
TI  - Very heavy computer and internet usage as a risk factor for schizophrenia in
      intelligent young males.

PMID- 22403395
TI  - Modelling coronary heart disease mortality in Northern Ireland between 1987 and
      2007: broader lessons for prevention.
AB  - AIMS: To quantify how much of the coronary heart disease (CHD) mortality decline
      in Northern Ireland between 1987 and 2007 could be attributed to medical and
      surgical treatments and how much to changes in population cardiovascular risk
      factors. METHODS AND RESULTS: The IMPACT mortality model was used to integrate
      data on uptake and effectiveness of cardiological treatments and risk factor
      trends in the Northern Ireland population between 1987 and 2007. The main data
      sources were official population and mortality statistics, hospital
      administration systems, primary care datasets, published trials and meta
      analyses, clinical audits, and national surveys. Between 1987 and 2007, CHD
      mortality rates in Northern Ireland decreased by 52% in men and 60% in women aged
      25-84 years. This resulted in 3180 fewer deaths in 2007 than expected if 1987
      mortality rates had persisted. Approximately 35% of this decrease was attributed
      to increased uptake of treatments in individuals and 60% to population risk
      factor reductions (principally blood pressure, total cholesterol, and smoking);
      however, these reductions were partially offset by adverse trends in diabetes,
      physical inactivity, and obesity. CONCLUSION: Approximately 60% of the
      substantial CHD mortality decline in Northern Ireland between 1987 and 2007 was
      attributable to major cardiovascular risk factor changes and approximately 35%
      was attributable to treatments. However, adverse trends in diabetes, obesity, and
      physical inactivity are of major concern.

PMID- 22403396
TI  - Progesterone and DNA damage encourage uterine cell proliferation and
      decidualization through up-regulating ribonucleotide reductase 2 expression
      during early pregnancy in mice.
AB  - Embryo implantation into the maternal uterus is a crucial step for the successful
      establishment of mammalian pregnancy. Following the attachment of embryo to the
      uterine luminal epithelium, uterine stromal cells undergo steroid hormone
      dependent decidualization, which is characterized by stromal cell proliferation
      and differentiation. The mechanisms underlying steroid hormone-induced stromal
      cell proliferation and differentiation during decidualization are still poorly
      understood. Ribonucleotide reductase, consisting of two subunits (RRM1 and RRM2),
      is a rate-limiting enzyme in deoxynucleotide production for DNA synthesis and
      plays an important role in cell proliferation and tumorgenicity. Based on our
      microarray analysis, Rrm2 expression was significantly higher at implantation
      sites compared with interimplantation sites in mouse uterus. However, the
      expression, regulation, and function of RRM2 in mouse uterus during embryo
      implantation and decidualization are still unknown. Here we show that although
      both RRM1 and RRM2 expression are markedly induced in mouse uterine stromal cells
      undergoing decidualization, only RRM2 is regulated by progesterone, a key
      regulator of decidualization. Further studies showed that the induction of
      progesterone on RRM2 expression in stromal cells is mediated by the AKT/c-MYC
      pathway. RRM2 can also be induced by replication stress and DNA damage during
      decidualization through the ATR/ATM-CHK1-E2F1 pathway. The weight of implantation
      sites and deciduoma was effectively reduced by specific inhibitors for RRM2. The
      expression of decidual/trophoblast prolactin-related protein (Dtprp), a reliable
      marker for decidualization in mice, was significantly reduced in deciduoma and
      steroid-induced decidual cells after HU treatment. Therefore, RRM2 may be an
      important effector of progesterone signaling to induce cell proliferation and
      decidualization in mouse uterus.

PMID- 22403397
TI  - NEU1 and NEU3 sialidase activity expressed in human lung microvascular
      endothelia: NEU1 restrains endothelial cell migration, whereas NEU3 does not.
AB  - The microvascular endothelial surface expresses multiple molecules whose
      sialylation state regulates multiple aspects of endothelial function. To better
      regulate these sialoproteins, we asked whether endothelial cells (ECs) might
      express one or more catalytically active sialidases. Human lung microvascular EC
      lysates contained heat-labile sialidase activity for a fluorogenic substrate, 2'
      (4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid (4-MU-NANA), that was dose
      dependently inhibited by the competitive sialidase inhibitor, 2,3-dehydro-2-deoxy
      N-acetylneuraminic acid but not its negative control. The EC lysates also
      contained sialidase activity for a ganglioside mixture. Using real time RT-PCR to
      detect mRNAs for the four known mammalian sialidases, NEU1, -2, -3, and -4, NEU1
      mRNA was expressed at levels 2700-fold higher that those found for NEU2, -3, or 
      4. Western analyses indicated NEU1 and -3 protein expression. Using confocal
      microscopy and flow cytometry, NEU1 was immunolocalized to both the plasma
      membrane and the perinuclear region. NEU3 was detected both in the cytosol and
      nucleus. Prior siRNA-mediated knockdown of NEU1 and NEU3 each decreased EC
      sialidase activity for 4-MU-NANA by >65 and >17%, respectively, and for the
      ganglioside mixture by 0 and 40%, respectively. NEU1 overexpression in ECs
      reduced their migration into a wound by >40%, whereas NEU3 overexpression did
      not. Immunohistochemical studies of normal human tissues immunolocalized NEU1 and
      NEU3 proteins to both pulmonary and extrapulmonary vascular endothelia. These
      combined data indicate that human lung microvascular ECs as well as other
      endothelia express catalytically active NEU1 and NEU3. NEU1 restrains EC
      migration, whereas NEU3 does not.

PMID- 22403398
TI  - Small ubiquitin-like modifier (SUMO) modification of E1 Cys domain inhibits E1
      Cys domain enzymatic activity.
AB  - Although it is well established that ubiquitin-like modifications are tightly
      regulated, it has been unclear how their E1 activities are controlled. In this
      study, we found that the SAE2 subunit of the small ubiquitin-like modifier (SUMO)
      E1 is autoSUMOylated at residue Lys-236, and SUMOylation was catalyzed by Ubc9 at
      several additional Lys residues surrounding the catalytic Cys-173 of SAE2.
      AutoSUMOylation of SAE2 did not affect SUMO adenylation or formation of E1.SUMO
      thioester, but did significantly inhibit the transfer of SUMO from E1 to E2 and
      overall SUMO conjugations to target proteins due to the altered interaction
      between E1 and E2. Upon heat shock, SUMOylation of SAE2 was reduced, which
      corresponded with an increase in global SUMOylation, suggesting that SUMOylation
      of the Cys domain of SAE2 is a mechanism for "storing" a pool of E1 that can be
      quickly activated in response to environmental changes. This study is the first
      to show how E1 activity is controlled by post-translational modifications, and
      similar regulation likely exists across the homologous E1s of ubiquitin-like
      modifications.

PMID- 22403399
TI  - A2B adenosine receptor promotes mesenchymal stem cell differentiation to
      osteoblasts and bone formation in vivo.
AB  - The differentiation of osteoblasts from their precursors, mesenchymal stem cells,
      is an important component of bone homeostasis as well as fracture healing. The
      A2B adenosine receptor (A2BAR) is a Galpha(s)/alpha(q)-protein-coupled receptor
      that signals via cAMP. cAMP-mediated signaling has been demonstrated to regulate
      the differentiation of mesenchymal stem cells (MSCs) into various skeletal tissue
      lineages. Here, we studied the role of this receptor in the differentiation of
      MSCs to osteoblasts. In vitro differentiation of bone marrow-derived MSCs from
      A2BAR KO mice resulted in lower expression of osteoblast differentiation
      transcription factors and the development of fewer mineralized nodules, as
      compared with WT mice. The mechanism of effect involves, at least partially, cAMP
      as indicated by experiments involving activation of the A2BAR or addition of a
      cAMP analog during differentiation. Intriguingly, in vivo, microcomputed
      tomography analysis of adult femurs showed lower bone density in A2BAR KO mice as
      compared with WT. Furthermore, A2BAR KO mice display a delay in normal fracture
      physiology with lower expression of osteoblast differentiation genes. Thus, our
      study identified the A2BAR as a new regulator of osteoblast differentiation, bone
      formation, and fracture repair.

PMID- 22403400
TI  - Dual color photoactivation localization microscopy of cardiomyopathy-associated
      desmin mutants.
AB  - Mutations in the DES gene coding for the intermediate filament protein desmin may
      cause skeletal and cardiac myopathies, which are frequently characterized by
      cytoplasmic aggregates of desmin and associated proteins at the cellular level.
      By atomic force microscopy, we demonstrated filament formation defects of desmin
      mutants, associated with arrhythmogenic right ventricular cardiomyopathy. To
      understand the pathogenesis of this disease, it is essential to analyze desmin
      filament structures under conditions in which both healthy and mutant desmin are
      expressed at equimolar levels mimicking an in vivo situation. Here, we applied
      dual color photoactivation localization microscopy using photoactivatable
      fluorescent proteins genetically fused to desmin and characterized the
      heterozygous status in living cells lacking endogenous desmin. In addition, we
      applied fluorescence resonance energy transfer to unravel short distance
      structural patterns of desmin mutants in filaments. For the first time, we
      present consistent high resolution data on the structural effects of five
      heterozygous desmin mutations on filament formation in vitro and in living cells.
      Our results may contribute to the molecular understanding of the pathological
      filament formation defects of heterozygous DES mutations in cardiomyopathies.

PMID- 22403401
TI  - Three acyltransferases and nitrogen-responsive regulator are implicated in
      nitrogen starvation-induced triacylglycerol accumulation in Chlamydomonas.
AB  - Algae have recently gained attention as a potential source for biodiesel;
      however, much is still unknown about the biological triggers that cause the
      production of triacylglycerols. We used RNA-Seq as a tool for discovering genes
      responsible for triacylglycerol (TAG) production in Chlamydomonas and for the
      regulatory components that activate the pathway. Three genes encoding
      acyltransferases, DGAT1, DGTT1, and PDAT1, are induced by nitrogen starvation and
      are likely to have a role in TAG accumulation based on their patterns of
      expression. DGAT1 and DGTT1 also show increased mRNA abundance in other TAG
      accumulating conditions (minus sulfur, minus phosphorus, minus zinc, and minus
      iron). Insertional mutants, pdat1-1 and pdat1-2, accumulate 25% less TAG compared
      with the parent strain, CC-4425, which demonstrates the relevance of the trans
      acylation pathway in Chlamydomonas. The biochemical functions of DGTT1 and PDAT1
      were validated by rescue of oleic acid sensitivity and restoration of TAG
      accumulation in a yeast strain lacking all acyltransferase activity. Time course
      analyses suggest than a SQUAMOSA promoter-binding protein domain transcription
      factor, whose mRNA increases precede that of lipid biosynthesis genes like DGAT1,
      is a candidate regulator of the nitrogen deficiency responses. An insertional
      mutant, nrr1-1, accumulates only 50% of the TAG compared with the parental strain
      in nitrogen-starvation conditions and is unaffected by other nutrient stresses,
      suggesting the specificity of this regulator for nitrogen-deprivation conditions.

PMID- 22403402
TI  - The unfolded protein response regulates an angiogenic response by the kidney
      epithelium during ischemic stress.
AB  - Ischemic injuries permanently affect kidney tissue and challenge cell viability,
      promoting inflammation and fibrogenesis. Ischemia results in nutrient
      deprivation, which triggers endoplasmic reticulum stress, ultimately resulting in
      the unfolded protein response (UPR). The aim of this study was to test whether
      the UPR could promote an angiogenic response independently of the HIF-1alpha
      pathway during ischemic stress in the human kidney epithelium. Glucose
      deprivation induced the secretion of vascular endothelial growth factor A
      (VEGFA), basic fibroblast growth factor (bFGF) and angiogenin (ANG) in human
      kidney epithelial cells independently of HIF-1alpha. Glucose deprivation, but not
      hypoxia, triggered endoplasmic reticulum stress and activated the UPR. RNA
      interference-mediated inhibition of the gene encoding the kinase PERK decreased
      VEGFA and bFGF expression, but neither gene was affected by the inhibition of
      IRE1alpha or ATF6. Furthermore, we show that the expression of angiogenin, which
      inhibits protein synthesis, is regulated by both IRE1alpha and PERK, which could
      constitute a complementary function of the UPR in the repression of translation.
      In a rat model of acute ischemic stress, we show that the UPR is activated in
      parallel with VEGFA, bFGF, and ANG expression and independently of HIF-1alpha.

PMID- 22403403
TI  - Newly discovered viral E3 ligase pK3 induces endoplasmic reticulum-associated
      degradation of class I major histocompatibility proteins and their membrane-bound
      chaperones.
AB  - Viral immune invasion proteins are highly effective probes for studying
      physiological pathways. We report here the characterization of a new viral
      ubiquitin ligase pK3 expressed by rodent herpesvirus Peru (RHVP) that establishes
      acute and latent infection in laboratory mice. Our findings show that pK3 binds
      directly and specifically to class I major histocompatibility proteins (MHCI) in
      a transmembrane-dependent manner. This binding results in the rapid degradation
      of the pK3/MHCI complex by a mechanism dependent upon catalytically active pK3.
      Subsequently, the rapid degradation of pK3/MHCI secondarily causes the slow
      degradation of membrane bound components of the MHCI peptide loading complex,
      tapasin, and transporter associated with antigen processing (TAP). Interestingly,
      this secondary event occurs by cellular endoplasmic reticulum-associated
      degradation. Cumulatively, our findings show pK3 uses a unique mechanism of
      substrate detection and degradation compared with other viral or cellular E3
      ligases. More importantly, our findings reveal that in the absence of nascent
      MHCI proteins in the endoplasmic reticulum, the transmembrane proteins TAP and
      tapasin that facilitate peptide binding to MHCI proteins are degraded by cellular
      quality control mechanisms.

PMID- 22403405
TI  - Dissociation of ATP-binding cassette nucleotide-binding domain dimers into
      monomers during the hydrolysis cycle.
AB  - ATP-binding cassette (ABC) proteins have two nucleotide-binding domains (NBDs)
      that work as dimers to bind and hydrolyze ATP, but the molecular mechanism of
      nucleotide hydrolysis is controversial. In particular, it is still unresolved
      whether hydrolysis leads to dissociation of the ATP-induced dimers or opening of
      the dimers, with the NBDs remaining in contact during the hydrolysis cycle. We
      studied a prototypical ABC NBD, the Methanococcus jannaschii MJ0796, using
      spectroscopic techniques. We show that fluorescence from a tryptophan positioned
      at the dimer interface and luminescence resonance energy transfer between probes
      reacted with single-cysteine mutants can be used to follow NBD
      association/dissociation in real time. The intermonomer distances calculated from
      luminescence resonance energy transfer data indicate that the NBDs separate
      completely following ATP hydrolysis, instead of opening. The results support ABC
      protein NBD association/dissociation, as opposed to constant-contact models.

PMID- 22403404
TI  - Critical role for antiapoptotic Bcl-xL and Mcl-1 in human macrophage survival and
      cellular IAP1/2 (cIAP1/2) in resistance to HIV-Vpr-induced apoptosis.
AB  - Macrophages are resistant to HIV cytopathic effects, which contributes to viral
      persistence and reservoir formation. HIV viral protein R (Vpr) is a potent
      apoptosis-inducing agent for primary monocytes. Because the biologically active
      Vpr is found in serum and cerebrospinal fluid of HIV-infected patients, we
      investigated the apoptotic effect of Vpr on monocyte-derived macrophages and
      phorbol 12-myristate 13-acetate-activated THP1 macrophages. Our results show that
      primary monocytes and THP1 cells develop resistance to Vpr-induced apoptosis
      following differentiation into macrophages. To determine the effect of Vpr on the
      expression of antiapoptotic proteins, we show that in contrast to the
      undifferentiated cells, Vpr did not down-regulate the expression of antiapoptotic
      inhibitors of apoptosis (IAPs) and Bcl2 family members in macrophages, suggesting
      their involvement in resistance to Vpr-induced apoptosis. However, knocking down
      Bcl-xL and Mcl-1 proteins induced spontaneous apoptosis with no impact on
      susceptibility to Vpr-induced apoptosis. In contrast, down-regulation of cellular
      IAP1 (cIAP1) and cIAP2 by using siRNAs and SMAC (second mitochondria-derived
      activator of caspases) mimetic sensitized macrophages to Vpr-induced apoptosis.
      Overall, our results suggest that resistance to Vpr-induced apoptosis is
      specifically mediated by cIAP1/2 genes independent of Bcl-xL and Mcl-1, which
      play a key role in maintaining cell viability. Moreover, IAP modulation may be a
      potential strategy to eliminate HIV persistence in macrophages.

PMID- 22403406
TI  - Kif2C minimal functional domain has unusual nucleotide binding properties that
      are adapted to microtubule depolymerization.
AB  - The kinesin-13 Kif2C hydrolyzes ATP and uses the energy released to disassemble
      microtubules. The mechanism by which this is achieved remains elusive. Here we
      show that Kif2C-(sN+M), a monomeric construct consisting of the motor domain with
      the proximal part of the N-terminal Neck extension but devoid of its more distal,
      unstructured, and highly basic part, has a robust depolymerase activity. When
      detached from microtubules, the Kif2C-(sN+M) nucleotide-binding site is occupied
      by ATP at physiological concentrations of adenine nucleotides. As a consequence,
      Kif2C-(sN+M) starts its interaction with microtubules in that state, which
      differentiates kinesin-13s from motile kinesins. Moreover, in this ATP-bound
      conformational state, Kif2C-(sN+M) has a higher affinity for soluble tubulin
      compared with microtubules. We propose a mechanism in which, in the first step,
      the specificity of ATP-bound Kif2C for soluble tubulin causes it to stabilize a
      curved conformation of tubulin heterodimers at the ends of microtubules. Data
      from an ATPase-deficient Kif2C mutant suggest that, then, ATP hydrolysis precedes
      and is required for tubulin release to take place. Finally, comparison with Kif2C
      Motor indicates that the binding specificity for curved tubulin and, accordingly,
      the microtubule depolymerase activity are conferred to the motor domain by its N
      terminal Neck extension.

PMID- 22403407
TI  - Principal role of the arginine finger in rotary catalysis of F1-ATPase.
AB  - F(1)-ATPase (F(1)) is an ATP-driven rotary motor wherein the gamma subunit
      rotates against the surrounding alpha(3)beta(3) stator ring. The 3 catalytic
      sites of F(1) reside on the interface of the alpha and beta subunits of the
      alpha(3)beta(3) ring. While the catalytic residues predominantly reside on the
      beta subunit, the alpha subunit has 1 catalytically critical arginine, termed the
      arginine finger, with stereogeometric similarities with the arginine finger of G
      protein-activating proteins. However, the principal role of the arginine finger
      of F(1) remains controversial. We studied the role of the arginine finger by
      analyzing the rotation of a mutant F(1) with a lysine substitution of the
      arginine finger. The mutant showed a 350-fold longer catalytic pause than the
      wild-type; this pause was further lengthened by the slowly hydrolyzed ATP analog
      ATPgammaS. On the other hand, the mutant F(1) showed highly unidirectional
      rotation with a coupling ratio of 3 ATPs/turn, the same as wild-type, suggesting
      that cooperative torque generation by the 3 beta subunits was not impaired. The
      hybrid F(1) carrying a single copy of the alpha mutant revealed that the reaction
      step slowed by the mutation occurs at +200 degrees  from the binding angle of the
      mutant subunit. Thus, the principal role of the arginine finger is not to mediate
      cooperativity among the catalytic sites, but to enhance the rate of the ATP
      cleavage by stabilizing the transition state of ATP hydrolysis. Lysine
      substitution also caused frequent pauses because of severe ADP inhibition, and a
      slight decrease in ATP-binding rate.

PMID- 22403408
TI  - Peptides from second extracellular loop of C-C chemokine receptor type 5 (CCR5)
      inhibit diverse strains of HIV-1.
AB  - To initiate HIV entry, the HIV envelope protein gp120 must engage its primary
      receptor CD4 and a coreceptor CCR5 or CXCR4. In the absence of a high resolution
      structure of a gp120-coreceptor complex, biochemical studies of CCR5 have
      revealed the importance of its N terminus and second extracellular loop (ECL2) in
      binding gp120 and mediating viral entry. Using a panel of synthetic CCR5 ECL2
      derived peptides, we show that the C-terminal portion of ECL2 (2C, comprising
      amino acids Cys-178 to Lys-191) inhibit HIV-1 entry of both CCR5- and CXCR4-using
      isolates at low micromolar concentrations. In functional viral assays, these
      peptides inhibited HIV-1 entry in a CD4-independent manner. Neutralization assays
      designed to measure the effects of CCR5 ECL2 peptides when combined with either
      with the small molecule CD4 mimetic NBD-556, soluble CD4, or the CCR5 N terminus
      showed additive inhibition for each, indicating that ECL2 binds gp120 at a site
      distinct from that of N terminus and acts independently of CD4. Using saturation
      transfer difference NMR, we determined the region of CCR5 ECL2 used for binding
      gp120, showed that it can bind to gp120 from both R5 and X4 isolates, and
      demonstrated that the peptide interacts with a CD4-gp120 complex in a similar
      manner as to gp120 alone. As the CCR5 N terminus-gp120 interactions are dependent
      on CD4 activation, our data suggest that gp120 has separate binding sites for the
      CCR5 N terminus and ECL2, the ECL2 binding site is present prior to CD4
      engagement, and it is conserved across CCR5- and CXCR4-using strains. These
      peptides may serve as a starting point for the design of inhibitors with broad
      spectrum anti-HIV activity.

PMID- 22403409
TI  - The protein phosphatase PP2A/Balpha binds to the microtubule-associated proteins
      Tau and MAP2 at a motif also recognized by the kinase Fyn: implications for
      tauopathies.
AB  - The predominant brain microtubule-associated proteins MAP2 and tau play a
      critical role in microtubule cytoskeletal organization and function. We have
      previously reported that PP2A/Balpha, a major protein phosphatase 2A (PP2A)
      holoenzyme, binds to and dephosphorylates tau, and regulates microtubule
      stability. Here, we provide evidence that MAP2 co-purifies with and is
      dephosphorylated by endogenous PP2A/Balpha in bovine gray matter. It co-localizes
      with PP2A/Balpha in immature and mature human neuronal cell bodies. PP2A co
      immunoprecipitates with and directly interacts with MAP2. Using in vitro binding
      assays, we show that PP2A/Balpha binds to MAP2c isoforms through a region
      encompassing the microtubule-binding domain and upstream proline-rich region. Tau
      and MAP2 compete for binding to and dephosphorylation by PP2A/Balpha. Remarkably,
      the protein-tyrosine kinase Fyn, which binds to the proline-rich RTPPKSP motif
      conserved in both MAP2 and tau, inhibits the interaction of PP2A/Balpha with
      either tau or MAP2c. The corresponding synthetic RTPPKSP peptide, but not the
      phosphorylated RpTPPKSP version, competes with Tau and MAP2c for binding to
      PP2A/Balpha. Significantly, down-regulation of PP2A/Balpha and deregulation of
      Fyn-Tau protein interactions have been linked to enhanced tau phosphorylation in
      Alzheimer disease. Together, our results suggest that PP2A/Balpha is part of
      segregated MAP2 and tau signaling scaffolds that can coordinate the action of key
      kinases and phosphatases involved in modulating neuronal plasticity. Deregulation
      of these compartmentalized multifunctional protein complexes is likely to
      contribute to tau deregulation, microtubule disruption, and altered signaling in
      tauopathies.

PMID- 22403410
TI  - Role for two conserved intermembrane space proteins, Ups1p and Ups2p, [corrected]
      in intra-mitochondrial phospholipid trafficking.
AB  - Mitochondrial membranes maintain a specific phospholipid composition. Most
      phospholipids are synthesized in the endoplasmic reticulum (ER) and transported
      to mitochondria, but cardiolipin and phosphatidylethanolamine are produced in
      mitochondria. In the yeast Saccharomyces cerevisiae, phospholipid exchange
      between the ER and mitochondria relies on the ER-mitochondria encounter structure
      (ERMES) complex, which physically connects the ER and mitochondrial outer
      membrane. However, the proteins and mechanisms involved in phospholipid transport
      within mitochondria remain elusive. Here, we investigated the role of the
      conserved intermembrane space proteins, Ups1p and Ups2p, and an inner membrane
      protein, Mdm31p, in phospholipid metabolism. Our data show that loss of the ERMES
      complex, Ups1p, and Mdm31p causes similar defects in mitochondrial phospholipid
      metabolism, mitochondrial morphology, and cell growth. Defects in cells lacking
      the ERMES complex or Ups1p are suppressed by Mdm31p overexpression as well as
      additional loss of Ups2p, which antagonizes Ups1p. Combined loss of the ERMES
      complex and Ups1p exacerbates phospholipid defects. Finally, pulse-chase
      experiments using [(14)C]serine revealed that Ups1p and Ups2p antagonistically
      regulate conversion of phosphatidylethanolamine to phosphatidylcholine. Our
      results suggest that Ups proteins and Mdm31p play important roles in phospholipid
      biosynthesis in mitochondria. Ups proteins may function in phospholipid
      trafficking between the outer and inner mitochondrial membranes.

PMID- 22403411
TI  - High-throughput transfection of differentiated primary neurons from rat
      forebrain.
AB  - Primary neurons in culture are considered to be a highly relevant model in the
      study of neuronal development and activity. They can be cultivated and
      differentiated in vitro but are difficult to transfect using conventional
      methods. To address this problem, a capillary electroporation system called
      Cellaxess Elektra was developed for efficient and reproducible transfection of
      primary cortical and hippocampal neurons without significant impact on cell
      morphology and viability. The cells are transfected in any stage of
      differentiation and development, directly in cell culture plates. Genetic
      material is delivered in situ to as many as 384 samples at a time, which enables
      both high-throughput and high-quality screening for hard-to-transfect primary
      cells, meaning that gene function can be studied on a genome-wide scale in cells
      previously inaccessible to genetic manipulation.

PMID- 22403412
TI  - Antibacterial nanocomposite with calcium phosphate and quaternary ammonium.
AB  - Secondary caries is a frequent reason for restoration failure, resulting from
      acidogenic bacteria and their biofilms. The objectives of this study were to: (1)
      develop a novel nanocomposite containing nanoparticles of amorphous calcium
      phosphate (NACP) and quaternary ammonium dimethacrylate (QADM); and (2)
      investigate its mechanical and antibacterial durability. A spray-drying technique
      yielded NACP with particle size of 116 nm. The nanocomposite contained NACP and
      reinforcement glass fillers, with QADM in the resin. Two commercial composites
      were tested as controls. Composites were inoculated with Streptococcus mutans.
      After 180-day water-aging, NACP+QADM nanocomposite had flexural strength and
      elastic modulus matching those of commercial controls (p > 0.1). NACP+QADM
      nanocomposite reduced the biofilm colony-forming units (CFU) by 3-fold, compared
      with commercial composites (p < 0.05). Metabolic activity and lactic acid
      production of biofilms on NACP+QADM were much less than those on commercial
      composites (p < 0.05). The antibacterial properties of NACP+QADM were maintained
      after water-aging for 30, 90, and 180 d (p > 0.05). In conclusion, the novel NACP
      QADM nanocomposite greatly decreased biofilm metabolic activity, CFU, and lactic
      acid, while matching the load-bearing capability of commercial composites without
      antibacterial properties. The NACP-QADM nanocomposite with strong and durable
      antibacterial properties, together with its previously reported Ca-PO(4) release
      capability, may render it useful for caries-inhibiting restorations.

PMID- 22403413
TI  - Survey of the feline leukemia virus infection status of cats in Southern Germany.
AB  - Most studies that investigate the prevalence of infections with feline leukemia
      virus (FeLV) are based on the detection of p27 antigen in blood, but they do not
      detect proviral DNA to identify the prevalence of regressive FeLV infections. The
      aim of the present study was to assess the prevalence and status of FeLV
      infection in cats in Southern Germany. P27 antigen enzyme-linked immunosorbent
      assay (ELISA), anti-p45 antibody ELISA, DNA polymerase chain reaction (PCR) of
      blood and RNA PCR of saliva were performed. Nine out of 495 cats were
      progressively (persistently) infected (1.8%) and six were regressively (latently)
      infected (1.2%). Cats with regressive infections are defined as cats that have
      been able to overcome antigenemia but provirus can be detected by PCR. Twenty-two
      unvaccinated cats likely had abortive infections (regressor cats), testing FeLV
      antigen- and provirus-negative but anti-p45 antibody-positive. Most of the FeLV
      vaccinated cats did not have anti-FeLV antibodies. Both progressive, as well as
      regressive infections seem to be rare in Germany today.

PMID- 22403414
TI  - Comparison of two formulations of buprenorphine in cats administered by the oral
      transmucosal route.
AB  - This randomised, blinded, cross-over study investigated the ease of oral
      transmucosal administration of two formulations of buprenorphine using glucose as
      a control in 12 cats. The cats received three treatments: buprenorphine multi
      dose, buprenorphine and the equivalent volume of glucose 5%. Ease of treatment
      administration, observation of swallowing, changes in pupil size, sedation,
      salivation, vomiting, behaviour and food intake were assessed. The data were
      analysed using MLwiN and multi-level modelling. Ease of administration of
      buprenorphine multi-dose was statistically different from glucose (P <0.001), and
      the administration of all treatments became easier over the study periods.
      Swallowing was not statistically different between groups (P >0.05). Mydriasis
      was evident after the administration of both formulations of buprenorphine.
      Sedation, salivation, vomiting, behavioural changes or in-appetence were not
      observed after any treatment. Cats tolerated oral transmucosal administration of
      glucose better than buprenorphine multi-dose, while buprenorphine administration
      was tolerated as well as glucose.

PMID- 22403415
TI  - Wedge meatoplasty as a treatment for stricture of the urethral meatus in a cat.
AB  - A three-and-a-half-year-old male neutered Siamese cat presented with idiopathic
      feline lower urinary tract inflammation and dysuria, which appeared to be caused
      by stricture of the urethral meatus. Wedge meatoplasty was performed, which
      relieved the cat's dysuria and restored a normal urine stream. To my knowledge,
      this is the first report of meatoplasty as a treatment for stricture of the
      urethral meatus in a cat.

PMID- 22403416
TI  - Single dose pharmacokinetics of terbinafine in cats.
AB  - The pharmacokinetics of terbinafine was studied in six healthy fasted cats
      following a single intravenous and oral administration at a dose of 10 mg/kg and
      30 mg/kg, respectively, according to a two-period crossover design. Plasma
      terbinafine concentrations were determined using a reverse phase liquid
      chromatographic method. The pharmacokinetic parameters were calculated by non
      compartmental analysis with WinNonlin 5.2.1 software. After intravenous
      administration, the terminal half-life and area under the curve from time 0 to
      infinity were 10.40 +/- 4.56 h, 15.20 +/- 3.61 h.ug/ml, respectively. After oral
      dosing, the mean maximum concentration was 3.22 +/- 0.60 ug/ml, reached at 1.33
      +/- 0.41 h. The terminal half-life, area under the curve from time 0 to infinity
      and apparent volume of distribution were 8.01 +/- 3.46 h, 13.77 +/- 4.99 h.ug/ml,
      25.63 +/- 6.29 l/kg, respectively. The absolute bioavailability of terbinafine
      hydrochloride tablets after oral administration was 31.00 +/- 10.85%. Although
      bioavailability was low, excellent penetration at the site of infection and low
      minimum inhibitory concentrations values provided terbinafine with good efficacy
      against dermatophyte infections.

PMID- 22403417
TI  - Multicytokine detection improves latent tuberculosis diagnosis in health care
      workers.
AB  - In a low-incidence setting, health care workers (HCW) are at a higher risk of
      tuberculosis than the general population. The suboptimal sensitivity of the
      QuantiFERON-TB Gold In-Tube (QFT) test remains a critical issue when identifying
      occupational latent tuberculosis infection (LTBI) in HCW. The aim of this study
      was to identify additional biomarkers in order to overcome the limits of gamma
      interferon (IFN-gamma) release assays (IGRAs) and improve the performance of LTBI
      diagnosis within this population. Seventy Bacille Calmette-Guerin-vaccinated HCW
      regularly exposed to Mycobacterium tuberculosis were grouped according to QFT
      results into an LTBI-positive group (positive QFT, n = 8), an LTBI-negative group
      (normal QFT and negative tuberculin skin test [TST], n = 21), and an undetermined
      group (subpositive QFT and/or positive TST, n = 41). The secretion of 22
      cytokines in response to QFT-specific stimulation was quantified using a
      multiparameter-based immunoassay. As a result, thresholds discriminating LTBI
      positive from LTBI-negative HCW were established by comparing areas under the
      receiver operating characteristic curves for interleukin-2 (IL-2), IL-15, IFN
      gamma-induced protein 10 (IP-10), and the monokine induced by IFN-gamma (MIG),
      which are biomarkers differentially secreted by the two groups. The combination
      of IL-15 and MIG provided a sensitivity of 100% and a specificity of 94.1% in
      distinguishing LTBI-positive from LTBI-negative HCW. When using IL-15 and MIG
      among the undetermined group, 6/45 HCW could be classified in the LTBI-positive
      group. The use of additional biomarkers after IGRA screening could improve the
      diagnosis of LTBI. The performance of these biomarkers and their use in
      combination with TST and/or QFT, as well as the cost-effectiveness of such a
      diagnostic strategy, should be evaluated in further larger clinical trials.

PMID- 22403418
TI  - Real-time PCR assay for identification of Blastomyces dermatitidis in culture and
      in tissue.
AB  - The TaqMan real-time PCR assay was developed from the Blastomyces dermatitidis
      BAD1 gene promoter. The assay identified all haplotypes of B. dermatitidis and
      five of six positive paraffin-embedded tissues. The assay sensitivity threshold
      was 1 pg genomic DNA of the mold form and 2 CFU of the yeast form of B.
      dermatitidis. No cross-reactivity was observed against other fungal DNA. The
      assay allowed rapid (5-h) identification of B. dermatitidis from culture and from
      clinical specimens.

PMID- 22403419
TI  - Molecular fingerprinting of Mycobacterium abscessus strains in a cohort of
      pediatric cystic fibrosis patients.
AB  - Forty-one Mycobacterium abscessus complex isolates from 17 pediatric cystic
      fibrosis (CF) patients were typed using a novel variable-number tandem repeat
      (VNTR) scheme and an automated repetitive-PCR (rep-PCR) system. Both VNTR and rep
      PCR typing methods differentiate between members of the M. abscessus complex. The
      isolates from individual patients are indistinguishable, and the data strongly
      suggest that individual CF patients are persistently infected with one strain and
      also suggests that different CF patients can harbor the same strain.

PMID- 22403420
TI  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      analysis of Gram-positive, catalase-negative cocci not belonging to the
      Streptococcus or Enterococcus genus and benefits of database extension.
AB  - Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass
      spectrometry with a Bruker Daltonics microflex LT system was applied to 90 well
      characterized catalase-negative, Gram-positive cocci not belonging to the
      streptococci or enterococci. Biotyper version 2.0.43.1 software was used singly
      or in combination with a database extension generated in this study with 51
      collection strains from 16 genera. Most strains were identified by using both
      databases individually, and some were identified only by applying the combined
      database. Thus, the methodology is very useful and the generated database
      extension was helpful.

PMID- 22403421
TI  - Evaluation of the GenBank, EzTaxon, and BIBI services for molecular
      identification of clinical blood culture isolates that were unidentifiable or
      misidentified by conventional methods.
AB  - We compared the 16S rRNA gene sequencing results analyzed with the GenBank,
      EzTaxon, and BIBI databases for blood culture specimens for which identifications
      were incomplete, conflicting, or unidentifiable using conventional methods.
      Analyses performed using GenBank combined with EzTaxon (kappa = 0.79) were more
      discriminative than those using other databases alone or in combination with a
      second database.

PMID- 22403422
TI  - Fecal carriage of carbapenemase-producing Enterobacteriaceae: a hidden reservoir
      in hospitalized and nonhospitalized patients.
AB  - Fecal carriage of carbapenemase-producing Enterobacteriaceae (CPE) has not been
      extensively investigated, except in the cases of selected patients at risk,
      mostly during outbreaks. A total of 1,100 fecal samples randomly collected in our
      institution in two different periods in 2006 (n = 600) and 2009-2010 (n = 500)
      from hospitalized (26.8%) and nonhospitalized (73.2%) patients were screened for
      CPE. The first period coincided with an outbreak of VIM-1-producing
      Enterobacteriaceae, and the second one coincided with the emergence of KPC
      enzymes in our hospital. Diluted samples in saline were cultured in Luria-Bertani
      broth with 1 MUg/ml imipenem and subcultured in MacConkey agar plates with 4
      MUg/ml ceftazidime. Growing colonies were screened for CPE (modified Hodge test
      and EDTA and boronic acid synergy tests). Carbapenemase genes, plasmids in which
      they are located, and clonal relatedness were determined. Individuals who
      exhibited fecal carriage of CPE (11/1,043, 1.1%; 95% confidence interval [CI],
      0.53 to 1.88) included 8 hospitalized (carriage rate, 2.9%; 95% CI, 1.24 to 5.55)
      and 3 nonhospitalized patients (carriage rate, 0.4%; 95% CI, 0.08 to 1.14), the
      latter being identified in 2009. Eighty-two percent of colonized patients were
      not infected with CPE. Isolates harboring bla(VIM-1) with or without bla(SHV-12)
      were identified as Klebsiella pneumoniae (n = 8; ST39, ST688, ST253, and ST163),
      Enterobacter cloacae (n = 3; two pulsed-field gel electrophoresis [PFGE] types),
      Escherichia coli (n = 2; ST155 and ST2441), and Citrobacter freundii (n = 1).
      Some of these lineages had previously been detected in our institution. The
      bla(VIM-1) gene was a member of the class 1 integrons In110 (bla(VIM-1)-aacA4
      aadA1) and In113 (bla(VIM-1)-aacA4-dhfrII) located on plasmids IncN (n = 11; 30
      to 50 kb) and IncHI2 (n = 3; 300 kb), respectively. Dissemination of bla(VIM-1)
      class-1 integrons within highly transferable plasmids in a polyclonal population
      has potentially contributed to the maintenance and spread of CPE.

PMID- 22403423
TI  - Characterization of microbiota of root canal-treated teeth with posttreatment
      disease.
AB  - This study evaluated the microbiota of root canals undergoing retreatment. The
      most prevalent taxa detected by checkerboard included Propionibacterium species,
      Fusobacterium nucleatum, streptococci, and Pseudoramibacter alactolyticus.
      Quantitative real-time PCR detected Enterococcus faecalis and streptococci in 38%
      and 41% of the cases, comprising 9.76% and 65.78% of the total bacterial counts,
      respectively. The findings call into question the status of E. faecalis as the
      main pathogen and suggest that other species can be candidate pathogens
      associated with persistent/secondary endodontic infections.

PMID- 22403424
TI  - Analysis of transmitted resistance to raltegravir and selective pressure among
      HIV-1-infected patients on a failing HAART in Sao Paulo, Brazil.
AB  - We studied the presence of primary resistance to raltegravir (RAL), natural
      polymorphisms, and selection pressure on HIV-1 integrase. We found a high
      frequency of integrase polymorphisms related to the resistance to RAL and
      sequence stability. Further studies are needed to determine the importance of
      these polymorphisms to RAL resistance.

PMID- 22403425
TI  - A novel delta-hemolysis screening method for detecting heteroresistant vancomycin
      intermediate Staphylococcus aureus and vancomycin-intermediate S. aureus.
AB  - We assessed a new screening method, based on delta-hemolysin production in the
      presence of 6 mg/liter vancomycin, to distinguish heteroresistant vancomycin
      intermediate Staphylococcus aureus (hVISA) and vancomycin-intermediate S. aureus
      (VISA) from vancomycin-susceptible S. aureus (VSSA). On 37 clinical methicillin
      resistant S. aureus (MRSA) isolates, hVISA and VISA displayed no delta-hemolysis
      whereas VSSA displayed strong delta-hemolysis, showing 91.6% sensitivity. These
      data, supported by real-time reverse transcription PCR (real-time RT-PCR)
      highlighting an hld downregulation, i.e., VSSA>hVISA>VISA, define this new assay
      as a valid screening method.

PMID- 22403426
TI  - A new and frequent human T-cell leukemia virus indeterminate Western blot
      pattern: epidemiological determinants and PCR results in central African
      inhabitants.
AB  - Human T-cell leukemia virus (HTLV) indeterminate Western blot (WB) serological
      patterns are frequently observed in plasma/serum from persons living in
      intertropical areas. In the framework of ongoing projects on HTLV-1/2 and related
      viruses in Central Africa, we systematically analyzed plasma from villagers
      living in South Cameroon by WB. The group included 1,968 individuals (mean age,
      44 years; age range, 5 to 90 years; 978 women/990 men), both Bantus (1,165) and
      Pygmies (803). Plasma samples were tested by WB analysis (MPD HTLV Blot 2.4) and
      interpreted according to the manufacturer's instructions. Only clear bands were
      considered in the analysis. Among the 1,968 plasma samples, 38 (1.93%) were HTLV
      1, 13 (0.66%) were HTLV-2, and 6 (0.3%) were HTLV WB seropositive. Furthermore,
      1,292 (65.65%) samples were WB sero-indeterminate, including 104 (5.28%) with an
      HTLV-1 Gag-indeterminate pattern (HGIP) and 68 (3.45%) with a peculiar yet
      unreported pattern exhibiting mostly a strong shifted GD21 and a p28. The other
      619 (31.45%) samples were either WB negative or exhibited other patterns, mostly
      with unique p19 or p24 bands. DNA, extracted from peripheral blood buffy coat,
      was subjected to PCR using several primer pairs known to detect HTLV-1/2/3/4.
      Most DNAs from HTLV-1- and HTLV-seropositive individuals were PCR positive. In
      contrast, all the others, from persons with HTLV-2, HGIP, new WB, and other
      indeterminate patterns, were PCR negative. Epidemiological determinant analysis
      of the persons with this new peculiar WB pattern revealed that seroprevalence was
      independent from age, sex, or ethnicity, thus resembling the indeterminate
      profile HGIP rather than HTLV-1. Moreover, this new pattern persists over time.

PMID- 22403427
TI  - Rapid identification of Sporothrix species by T3B fingerprinting.
AB  - This article describes PCR fingerprinting using the universal primer T3B to
      distinguish among species of the Sporothrix complex, S. brasiliensis, S. globosa,
      S. mexicana, and S. schenckii. This methodology generated distinct banding
      patterns, allowing the correct identification of all 35 clinical isolates at the
      species level, confirmed by partial calmodulin (CAL) gene sequence analyses. This
      methodology is simple, reliable, rapid, and cheap, making it an ideal routine
      identification system for clinical mycology laboratories.

PMID- 22403428
TI  - Performance of the novel Qiagen artus QS-RGQ viral load assays compared to that
      of the Abbott RealTime system with genetically diversified HIV and hepatitis C
      Virus plasma specimens.
AB  - We compared two novel Qiagen QS-RGQ viral load assays with the established Abbott
      RealTime assays on a highly diversified panel of 121 human immunodeficiency virus
      (HIV) and 107 hepatitis C virus (HCV) specimens. The quantifications correlated
      well for all HIV and HCV types, but Qiagen yielded higher HCV concentrations than
      Abbott, predominantly in genotypes 4 and 5.

PMID- 22403429
TI  - Incidence of recent human immunodeficiency virus infection at two voluntary
      counseling testing centers in Pernambuco, Brazil, from 2006 to 2009.
AB  - This study shows HIV-1 incidence in the northeastern region of Brazil, where the
      HIV epidemic has spread recently. Incidence was higher among men (1.34%; 95%
      confidence interval [CI], 1.00% to 1.69%) than among women (0.55%; 95% CI, 0.43%
      to 0.68%) (P < 0.0001), and there was an association between younger age and
      recent HIV infection (P < 0.004).

PMID- 22403430
TI  - Simultaneously high prevalences of hepatitis B and C virus infections in a
      population in Putian County, China.
AB  - This study investigated a rare area of endemicity with a high prevalence of both
      hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, in Putian County,
      China. Among 1,050 subjects, the overall prevalence of HBsAg seropositivity was
      15.8%, and that of anti-HCV seropositivity was 28.9%. Intrafamilial viral
      transmission might be the major cause of the high prevalence of HBV infection in
      this region. However, HCV infection was shown to be associated with the use of
      inadequately sterilized medical equipment.

PMID- 22403432
TI  - Microbial amelioration of crop salinity stress.
AB  - The use of soil and irrigation water with a high content of soluble salts is a
      major limiting factor for crop productivity in the semi-arid areas of the world.
      While important physiological insights about the mechanisms of salt tolerance in
      plants have been gained, the transfer of such knowledge into crop improvement has
      been limited. The identification and exploitation of soil microorganisms
      (especially rhizosphere bacteria and mycorrhizal fungi) that interact with plants
      by alleviating stress opens new alternatives for a pyramiding strategy against
      salinity, as well as new approaches to discover new mechanisms involved in stress
      tolerance. Although these mechanisms are not always well understood, beneficial
      physiological effects include improved nutrient and water uptake, growth
      promotion, and alteration of plant hormonal status and metabolism. This review
      aims to evaluate the beneficial effects of soil biota on the plant response to
      saline stress, with special reference to phytohormonal signalling mechanisms that
      interact with key physiological processes to improve plant tolerance to the
      osmotic and toxic components of salinity. Improved plant nutrition is a quite
      general beneficial effect and may contribute to the maintenance of homeostasis of
      toxic ions under saline stress. Furthermore, alteration of crop hormonal status
      to decrease evolution of the growth-retarding and senescence-inducing hormone
      ethylene (or its precursor 1-aminocyclopropane-1-carboxylic acid), or to maintain
      source-sink relations, photosynthesis, and biomass production and allocation (by
      altering indole-3-acetic acid and cytokinin biosynthesis) seem to be promising
      target processes for soil biota-improved crop salt tolerance.

PMID- 22403431
TI  - Automating HIV drug resistance genotyping with RECall, a freely accessible
      sequence analysis tool.
AB  - Genotypic HIV drug resistance testing is routinely used to guide clinical
      decisions. While genotyping methods can be standardized, a slow, labor-intensive,
      and subjective manual sequence interpretation step is required. We therefore
      performed external validation of our custom software RECall, a fully automated
      sequence analysis pipeline. HIV-1 drug resistance genotyping was performed on 981
      clinical samples at the Stanford Diagnostic Virology Laboratory. Sequencing trace
      files were first interpreted manually by a laboratory technician and subsequently
      reanalyzed by RECall, without intervention. The relative performances of the two
      methods were assessed by determination of the concordance of nucleotide base
      calls, identification of key resistance-associated substitutions, and HIV drug
      resistance susceptibility scoring by the Stanford Sierra algorithm. RECall is
      freely available at http://pssm.cfenet.ubc.ca. In total, 875 of 981 sequences
      were analyzed by both human and RECall interpretation. RECall analysis required
      minimal hands-on time and resulted in a 25-fold improvement in processing speed
      (~150 technician-hours versus ~6 computation-hours). Excellent concordance was
      obtained between human and automated RECall interpretation (99.7% agreement for
      >1,000,000 bases compared). Nearly all discordances (99.4%) were due to
      nucleotide mixtures being called by one method but not the other. Similarly,
      98.6% of key antiretroviral resistance-associated mutations observed were
      identified by both methods, resulting in 98.5% concordance of resistance
      susceptibility interpretations. This automated sequence analysis tool provides
      both standardization of analysis and a significant improvement in data workflow.
      The time-consuming, error-prone, and dreadfully boring manual sequence analysis
      step is replaced with a fully automated system without compromising the accuracy
      of reported HIV drug resistance data.

PMID- 22403433
TI  - Dislocation of the unossified epiphysis of the distal phalanx of a finger.

PMID- 22403434
TI  - A technique for accurately marking the A1 pulley on the skin.

PMID- 22403435
TI  - Development of a special needle knife for percutaneous A1 pulley release.

PMID- 22403436
TI  - A case of Kienbock's disease and hereditary spherocytosis anaemia.

PMID- 22403437
TI  - Fragment-specific fixation for complex intra-articular fractures of the distal
      radius: results of a prospective single-centre trial.
AB  - The goal was to evaluate the efficacy of 2.4 mm column-specific plating for intra
      articular distal radius fractures. In total, 105 patients with AO type C distal
      radius fractures were operated on using the locking distal radius system,
      Synthes. Follow-up assessments including clinical (wrist and forearm range of
      motion, grip strength), radiological (articular step, radial length and
      inclination, volar tilt, and ulnar variance), and functional scores (Disabilities
      of the Arm, Shoulder, and Hand; Patient Rated Wrist Evaluation) were made at
      regular intervals until 1 year. Union was obtained in all patients. Articular
      surface was anatomically reconstructed in 74 patients (70.5%). Clinical and
      functional evaluation showed significant continuous improvements over the first
      year. C1 fractures had a better chance of anatomical reduction compared with C2
      and C3 fractures. Fracture type, quality of reduction, and presence of
      degenerative changes did not show a significant effect on functional outcome
      scores. Column-specific fixation of the distal radius can achieve satisfactory
      results in complex intra-articular fractures.

PMID- 22403438
TI  - Nerve to brachialis transfer to axillary nerve.

PMID- 22403439
TI  - Caspase-1 has both proinflammatory and regulatory properties in Helicobacter
      infections, which are differentially mediated by its substrates IL-1beta and IL
      18.
AB  - The proinflammatory cysteine protease caspase-1 is autocatalytically activated
      upon cytosolic sensing of a variety of pathogen-associated molecular patterns by
      Nod-like receptors. Active caspase-1 processes pro-IL-1beta and pro-IL-18 to
      generate the bioactive cytokines and to initiate pathogen-specific immune
      responses. Little information is available on caspase-1 and inflammasome
      activation during infection with the gastric bacterial pathogen Helicobacter
      pylori. In this study, we addressed a possible role for caspase-1 and its
      cytokine substrates in the spontaneous and vaccine-induced control of
      Helicobacter infection, as well as the development of gastritis and gastric
      cancer precursor lesions, using a variety of experimental infection, vaccine
      induced protection, and gastric disease models. We show that caspase-1 is
      activated and IL-1beta and IL-18 are processed in vitro and in vivo as a
      consequence of Helicobacter infection. Caspase-1 activation and IL-1 signaling
      are absolutely required for the efficient control of Helicobacter infection in
      vaccinated mice. IL-1R(-/-) mice fail to develop protective immunity but are
      protected against Helicobacter-associated gastritis and gastric preneoplasia as a
      result of their inability to generate Helicobacter-specific Th1 and Th17
      responses. In contrast, IL-18 is dispensable for vaccine-induced protective
      immunity but essential for preventing excessive T cell-driven immunopathology. IL
      18(-/-) animals develop strongly accelerated pathology that is accompanied by
      unrestricted Th17 responses. In conclusion, we show in this study that the
      processing and release of a regulatory caspase-1 substrate, IL-18, counteracts
      the proinflammatory activities of another caspase-1 substrate, IL-1beta, thereby
      balancing control of the infection with the prevention of excessive gastric
      immunopathology.

PMID- 22403440
TI  - Protein kinase C-theta is required for murine neutrophil recruitment and adhesion
      strengthening under flow.
AB  - Protein kinase C (PKC)-theta is involved in T cell activation via regulating the
      avidity of the beta(2) integrin LFA-1 in the immunological synapse. LFA-1 also
      mediates leukocyte adhesion. To investigate the role of PKC-theta in neutrophil
      adhesion, we performed intravital microscopy in cremaster venules of mice
      reconstituted with bone marrow from LysM-GFP(+) (wild-type [WT]) and PKC-theta
      gene-deficient (Prkcq(-/-)) mice. Following stimulation with CXCL1, both WT and
      Prkcq(-/-) cells became adherent. Although most WT neutrophils remained adherent
      for at least 180 s, 50% of Prkcq(-/-) neutrophils were detached after 105 s and
      most by 180 s. Upon CXCL1 injection, rolling of all WT neutrophils stopped for 90
      s, but rolling of Prkcq(-/-) neutrophils started 30 s after CXCL1 stimulation. A
      similar neutrophil adhesion defect was seen in vitro, and spreading of Prkcq(-/-)
      neutrophils was delayed. Prkcq(-/-) neutrophil recruitment was impaired in fMLP
      induced transmigration into the cremaster muscle, thioglycollate-induced
      peritonitis, and LPS-induced lung injury. We conclude that PKC-theta mediates
      integrin-dependent neutrophil functions and is required to sustain neutrophil
      adhesion in postcapillary venules in vivo. These findings suggest that the role
      of PKC-theta in outside-in signaling following engagement of neutrophil integrins
      is relevant for inflammation in vivo.

PMID- 22403441
TI  - A unique role for ITK in survival of invariant NKT cells associated with the p53
      dependent pathway in mice.
AB  - Invariant NKT (iNKT) cells play important roles in the immune response. ITK and
      TXK/RLK are Tec family kinases that are expressed in iNKT cells; the expression
      level of ITK is ~7-fold higher than that of TXK. Itk(-/-) mice have reduced iNKT
      cell frequency and numbers, with defects in development and cytokine secretion
      that are exacerbated in Itk/Txk double-knockout mice. In contrast, there is no
      iNKT cell defect in Txk(-/-) mice. To determine whether ITK and TXK play distinct
      roles in iNKT cell development and function, we examined mice that overexpress
      TXK in T cells at levels similar to Itk. Overexpression of TXK rescues the
      maturation and cytokine secretion of Itk(-/-) iNKT cells, as well as altered
      expression of transcription factors T-bet, eomesodermin, and PLZF. In contrast,
      the increased apoptosis observed in Itk(-/-) splenic iNKT cells is not affected
      by TXK overexpression, likely due to the lack of effect on the elevated
      expression of p53 regulated proapoptotic pathways Fas, Bax, and Bad in those
      cells. Supporting this idea, p53(-/-) and Bax(-/-) mice have increased splenic
      iNKT cells. Our results suggest that TXK plays an overlapping role with ITK in
      iNKT cell development and function but that ITK also has a unique function in the
      survival of iNKT cells, likely via a p53-dependent pathway.

PMID- 22403443
TI  - Involvement of an NKG2D ligand H60c in epidermal dendritic T cell-mediated wound
      repair.
AB  - Dendritic epidermal T cells (DETCs) found in mouse skin are NKG2D-positive
      gammadelta T cells involved in immune surveillance and wound repair. It is
      assumed that the interaction of an NKG2D receptor on DETCs and an MHC class I
      like NKG2D ligand on keratinocytes activates DETCs, which then secrete cytokines
      promoting wound repair. However, direct evidence that DETC activation through
      NKG2D signaling promotes wound repair is not available. In the present study, we
      generated mAbs for an NKG2D ligand H60c previously suggested to be expressed
      specifically on skin keratinocytes. Local administration of H60c-specific mAb
      inhibited activation of DETCs and significantly delayed wound repair. Likewise,
      administration of NKG2D-specific mAb impaired wound repair to a similar extent.
      The delay in wound closure resulting from the blockade of the NKG2D pathway was
      comparable to that observed in gammadelta T cell-deficient mice. These results
      indicate that H60c/NKG2D interactions play a critical role in wound repair.
      Reassessment of binding affinities showed that H60c monomers bind to NKG2D with
      affinity (K(d) = 26 +/- 3.2 nM) comparable to those of other high-affinity NKG2D
      ligands. H60c is transcribed not only in skin but also in tissues such as tongue
      and female reproductive tract known to contain epithelium-resident gammadelta T
      cells expressing invariant TCRs, suggesting a more general role for H60c in the
      maintenance of epithelial integrity.

PMID- 22403442
TI  - Impaired IL-17 signaling pathway contributes to the increased collagen expression
      in scleroderma fibroblasts.
AB  - Among IL-17 families, IL-17A and IL-17F share amino acid sequence similarity and
      bind to IL-17R type A. IL-17 signaling is implicated in the pathogenesis of
      various autoimmune diseases, but its role in the regulatory mechanism of
      extracellular matrix expression and its contribution to the phenotype of systemic
      sclerosis (SSc) both remain to be elucidated. This study revealed that IL-17A
      expression was significantly increased in the involved skin and sera of SSc
      patients, whereas the IL-17F levels did not increase. In contrast, the expression
      of IL-17R type A in SSc fibroblasts significantly decreased in comparison with
      that in normal fibroblasts, due to the intrinsic TGF-beta1 activation in these
      cell types. Moreover, IL-17A, not IL-17F, reduced the protein expression of
      alpha1(I) collagen and connective tissue growth factor. miR-129-5p, one of the
      downregulated microRNAs in SSc fibroblasts, increased due to IL-17A and mediated
      the alpha1(I) collagen reduction. These results suggest that IL-17A signaling,
      not IL-17F, has an antifibrogenic effect via the upregulation of miR-129-5p and
      the downregulation of connective tissue growth factor and alpha1(I) collagen. IL
      17A signaling is suppressed due to the downregulation of the receptor by the
      intrinsic activation of TGF-beta1 in SSc fibroblasts, which may amplify the
      increased collagen accumulation and fibrosis characteristic of SSc. Increased IL
      17A levels in the sera and involved skin of SSc may be due to negative feedback.
      Clarifying the novel regulatory mechanisms of fibrosis by the cytokine network
      consisting of TGF-beta and IL-17A may lead to a new therapeutic approach for this
      disease.

PMID- 22403444
TI  - The E3 ubiquitin ligase adaptor Ndfip1 regulates Th17 differentiation by limiting
      the production of proinflammatory cytokines.
AB  - Ndfip1 is an adaptor for the E3 ubiquitin ligase Itch. Both Ndfip1- and Itch
      deficient T cells are biased toward Th2 cytokine production. In this study, we
      demonstrate that lungs from Ndfip1(-/-) mice showed increased numbers of
      neutrophils and Th17 cells. This was not because Ndfip1(-/-) T cells are biased
      toward Th17 differentiation. In fact, fewer Ndfip1(-/-) T cells differentiated
      into Th17 cells in vitro due to high IL-4 production. Rather, Th17
      differentiation was increased in Ndfip1(-/-) mice due to increased numbers of IL
      6-producing eosinophils. IL-6 levels in mice that lacked both Ndfip1 and IL-4
      were similar to wild-type controls, and these mice had fewer Th17 cells in their
      lungs. These results indicate that Th2 inflammation, such as that observed in
      Ndfip1(-/-) mice, can increase Th17 differentiation by recruiting IL-6-producing
      eosinophils into secondary lymphoid organs and tissues. This may explain why Th17
      cells develop within an ongoing Th2 inflammatory response.

PMID- 22403445
TI  - Formation of C-C Bonds via Catalytic Hydrogenation and Transfer Hydrogenation:
      Vinylation, Allylation, and Enolate Addition of Carbonyl Compounds and Imines.

PMID- 22403446
TI  - Functional analysis and treatment of arranging and ordering by individuals with
      an autism spectrum disorder.
AB  - Of the diagnostic features of autism, relatively little research has been devoted
      to restricted and repetitive behavior, particularly topographically complex forms
      of restricted and repetitive behavior such as rigidity in routines or compulsive
      like behavior (e.g., arranging objects in patterns or rows). Like vocal or motor
      stereotypy, topographically complex forms of restricted and repetitive behavior
      may be associated with negative outcomes such as interference with skill
      acquisition, negative social consequences, and severe problem behavior associated
      with interruption of restricted and repetitive behavior. In the present study, we
      extended functional analysis methodology to the assessment and treatment of
      arranging and ordering for 3 individuals with an autism spectrum disorder. For
      all 3 participants, arranging and ordering was found to be maintained by
      automatic reinforcement, and treatments based on function reduced arranging and
      ordering.

PMID- 22403447
TI  - Acquisition of social referencing via discrimination training in infants.
AB  - This experiment investigated social referencing as a form of discriminative
      learning in which maternal facial expressions signaled the consequences of the
      infant's behavior in an ambiguous context. Eleven 4- and 5-month-old infants and
      their mothers participated in a discrimination-training procedure using an ABAB
      design. Different consequences followed infants' reaching toward an unfamiliar
      object depending on the particular maternal facial expression. During the
      training phases, a joyful facial expression signaled positive reinforcement for
      the infant reaching for an ambiguous object, whereas a fearful expression
      signaled aversive stimulation for the same response. Baseline and extinction
      conditions were implemented as controls. Mothers' expressions acquired control
      over infants' approach behavior for all participants. All participants ceased to
      show discriminated responding during the extinction phase. The results suggest
      that 4- and 5-month-old infants can learn social referencing via discrimination
      training.

PMID- 22403448
TI  - Generalized instruction following with pictorial prompts.
AB  - The benefits of permanent pictorial prompts in enhancing maintenance and
      generalization are likely dependent on their degree of stimulus control and the
      extent to which their use is generalized. Although several studies on the use of
      pictorial prompts have demonstrated their efficacy (e.g., Pierce & Schreibman,
      1994; Wacker & Berg, 1983; Wacker, Berg, Berrie, & Swatta, 1985), there is still
      some question regarding what ultimately controlled responding. The present study
      allowed an explicit examination of stimulus control by pictorial prompts. Three 4
      year-old children with developmental disabilities were taught to complete 4
      instructional sets (5 steps each) using pictorial prompts such that the prompts
      would control responding. All 3 participants showed generalization to the final
      set after training with 3 sets. These results suggest that training a single task
      sequence may not be sufficient for acquisition of generalized pictorial
      instruction following. However, establishing stimulus control by the pictorial
      prompts rather than teaching behavioral chains may facilitate acquisition of a
      generalized repertoire.

PMID- 22403449
TI  - Analysis of self-recording in self-management interventions for stereotypy.
AB  - Most treatments for stereotypy involve arrangements of antecedent or consequent
      events that are imposed entirely by a therapist. By contrast, results of some
      studies suggest that self-recording, a common component of self-management
      interventions, might be an effective and efficient way to reduce stereotypy.
      Because the procedure typically has included instructions to refrain from
      stereotypy, self-recording of the absence of stereotypy, and differential
      reinforcement of accurate recording, it is unclear which element or combination
      of elements produces reductions in stereotypy. We conducted a component analysis
      of a self-management intervention and observed that decreases in stereotypy might
      be attributable to instructional control or to differential reinforcement, but
      that self-recording per se had little effect on stereotypy.

PMID- 22403450
TI  - Evaluation of a self-instruction package for conducting stimulus preference
      assessments.
AB  - Research suggests that inexperienced individuals cannot accurately implement
      stimulus preference assessments given written instructions alone. Training that
      includes written instructions supplemented with feedback from a professional with
      expertise in conducting preference assessments has proven effective;
      unfortunately, expert-facilitated direct training may not be widely available. In
      the current study, we used multiple baseline designs to evaluate the efficacy of
      an antecedent-only self-instructional package to train staff members to implement
      two methods of stimulus preference assessments. Accuracy was low when
      participants had access to written instructions alone. When access to enhanced
      written instructions was provided (i.e., technical jargon was minimized;
      instructions included pictures, diagrams, and step-by-step examples),
      inexperienced staff accurately implemented the assessments. Results are discussed
      in terms of opportunities to disseminate behavior-analytic technologies through
      self-instruction and print resources.

PMID- 22403451
TI  - Comparison of upright and flipped spoon presentations to guide treatment of food
      refusal.
AB  - The current study examined the effects of bite placement with a flipped versus
      upright spoon on expulsion and mouth clean (product measure of swallowing) in the
      treatment of 3 children diagnosed with a pediatric feeding disorder and oral
      motor deficits. For all 3 participants, extinction in the form of nonremoval of
      the spoon led to improvements in inappropriate mealtime behavior and acceptance
      of bites; however, re-presentation did not reduce expulsion or improve mouth
      clean. Results showed a lower level of expulsion and higher percentage of mouth
      clean during flipped spoon presentations and re-presentations for all
      participants. Findings from follow-up analyses supported transitioning back to an
      upright spoon in all 3 cases, although the time required for this to occur
      differed across participants.

PMID- 22403452
TI  - Using a chaser to decrease packing in children with feeding disorders.
AB  - Packing is a problematic mealtime behavior that is characterized by pocketing or
      holding solids or liquids in the mouth without swallowing. In the current study,
      we examined the effects of a chaser, a liquid or solid consistently accepted and
      swallowed by the child, to decrease packing of solid foods in 3 children with
      feeding disorders. During the chaser procedure, the therapist presented the
      chaser immediately for 2 children or 15 s after each bite presentation for 1
      child. The chaser was effective in decreasing packing for all 3 children. The
      results are discussed in terms of the clinical importance of the findings and
      directions for future research.

PMID- 22403453
TI  - The effects of verbal operant training and response interruption and redirection
      on appropriate and inappropriate vocalizations.
AB  - Past research has shown that response interruption and redirection (RIRD) can
      effectively decrease automatically reinforced motor behavior (Hagopian &
      Adelinis, 2001). Ahearn, Clark, MacDonald, and Chung (2007) found that a
      procedural adaptation of RIRD reduced vocal stereotypy and increased appropriate
      vocalizations for some children, although appropriate vocalizations were not
      targeted directly. The purpose of the current study was to examine the effects of
      directly targeting appropriate language (i.e., verbal operant training) on vocal
      stereotypy and appropriate speech in 3 children with an autism spectrum disorder.
      The effects of verbal operant (i.e., tact) training were evaluated in a
      nonconcurrent multiple baseline design across participants. In addition, RIRD was
      implemented with 2 of the 3 participants to further decrease levels of vocal
      stereotypy. Verbal operant training alone produced slightly lower levels of
      stereotypy and increased appropriate vocalizations for all 3 participants;
      however, RIRD was required to produce acceptably low levels of stereotypy for 2
      of the 3 participants.

PMID- 22403454
TI  - An analysis of modifications to the three-step guided compliance procedure
      necessary to achieve compliance among preschool children.
AB  - After a 3-step guided compliance procedure (vocal prompt, vocal plus model
      prompt, vocal prompt plus physical guidance) did not increase compliance, we
      evaluated 2 modifications with 4 preschool children who exhibited noncompliance.
      The first modification consisted of omission of the model prompt, and the second
      modification consisted of omitting the model prompt and decreasing the
      interprompt interval from 10 s to 5 s. Each of the modifications effectively
      increased compliance for 1 participant. For the remaining 2 participants, neither
      modification was effective; differential reinforcement in the form of contingent
      access to a preferred edible item was necessary to increase compliance. Problem
      behavior varied across participants, but was generally higher during guided
      compliance conditions and lower during differential reinforcement conditions.

PMID- 22403455
TI  - An evaluation of strengthening precursors to increase preschooler compliance.
AB  - We evaluated the strategy of increasing precursors to compliance on the
      compliance of 2 preschool boys. Modeling and differential reinforcement were used
      to increase specific responses to his name being called prior to the opportunity
      to comply with an instruction. The precursors were stopping the ongoing activity
      and orienting to, making eye contact with, and saying "yes" to the instructor.
      High levels of precursors occurred during treatment, and increases in compliance
      also were observed, even though the consequences for compliance and noncompliance
      did not change.

PMID- 22403456
TI  - An evaluation of progressively increasing intertrial intervals on the acquisition
      and generalization of three social skills.
AB  - We evaluated the effects of different intertrial intervals (ITIs; time between
      programmed learning opportunities) on the acquisition and generalization of 2
      preschoolers' social skills. Independent and generalized skills were observed
      only when the daily ITI was gradually increased from short to progressively
      longer intervals.

PMID- 22403457
TI  - Disruptive effects of contingent food on high-probability behavior.
AB  - The delivery of food contingent on 10 s of consecutive toy engagement resulted in
      a decrease in engagement and a corresponding increase in other responses that had
      been previously reinforced with food. Similar effects were not observed when
      tokens exchangeable for the same food were delivered, suggesting that engagement
      was disrupted by the contingent provision of the food, which may have functioned
      as a discriminative stimulus that occasioned competing responses.

PMID- 22403458
TI  - Using high-probability foods to increase the acceptance of low-probability foods.
AB  - Studies have evaluated a range of interventions to treat food selectivity in
      children with autism and related developmental disabilities. The high-probability
      instructional sequence is one intervention with variable results in this area. We
      evaluated the effectiveness of a high-probability sequence using 3 presentations
      of a preferred food on increasing acceptance in a child with autism who refused a
      few specific foods. The high-probability sequence increased acceptance of 3
      foods. We then systematically faded the intervention for 2 foods.

PMID- 22403459
TI  - A comparison of intraverbal training procedures for children with autism.
AB  - We compared the effectiveness of three training procedures, echoic and tact
      prompting plus error correction and a cues-pause-point (CPP) procedure, for
      increasing intraverbals in 2 children with autism. We also measured echoic
      behavior that may have interfered with appropriate question answering. Results
      indicated that echoic prompting with error correction was most effective and the
      CPP procedure was least effective for increasing intraverbals and decreasing
      echoic behavior.

PMID- 22403460
TI  - Voucher-based reinforcement for alcohol abstinence using the ethyl-glucuronide
      alcohol biomarker.
AB  - This study assessed the effects of a contingency management (CM) intervention for
      alcohol consumption in 10 alcohol-dependent participants. An ABCA design was
      used. Vouchers were provided contingent on results of ethyl glucuronide (EtG)
      urine tests (an alcohol biomarker with a 2-day detection period) and alcohol
      breath tests during the C phase. The percentage of negative urines was 35% during
      the first baseline phase, 69% during the C phase, and 20% during the return-to
      baseline phase. Results suggest that EtG urine tests may be a feasible method to
      deliver CM to promote alcohol abstinence.

PMID- 22403461
TI  - Teaching coin discrimination to children with visual impairments.
AB  - We taught 2 children with visual impairments to select a coin from an array using
      tactile cues after hearing its name and then to select a coin after hearing its
      value. Following the acquisition of these listener (receptive language) skills,
      we then observed the emergence of speaker (expressive language) skills without
      direct instruction.

PMID- 22403462
TI  - Examining the utility of the stimulus pairing observation procedure with
      preschool children learning a second language.
AB  - We evaluated the effectiveness of a stimulus pairing observation procedure to
      facilitate tact and listener relations in preschool children learning a second
      language. This procedure resulted in the establishment of most listener relations
      as well as some tact relations. Multiple-exemplar training resulted in the
      establishment of most of the remaining relations. The implications for the use of
      these procedures to establish simple vocabulary skills in children are discussed.

PMID- 22403463
TI  - Reducing covert self-injurious behavior maintained by automatic reinforcement
      through a variable momentary DRO procedure.
AB  - Covert self-injurious behavior (i.e., behavior that occurs in the absence of
      other people) can be difficult to treat. Traditional treatments typically have
      involved sophisticated methods of observation and often have employed positive
      punishment procedures. The current study evaluated the effectiveness of a
      variable momentary differential reinforcement contingency in the treatment of
      covert self-injury. Neither positive punishment nor extinction was required to
      produce decreased skin picking.

PMID- 22403464
TI  - Effects of three types of noncontingent auditory stimulation on vocal stereotypy
      in children with autism.
AB  - We evaluated the effects of 3 types of noncontingent auditory stimulation (music,
      white noise, recordings of vocal stereotypy) on 2 children with autism who
      engaged in high rates of vocal stereotypy. For both participants, the music
      condition was the most effective in decreasing vocal stereotypy to near-zero
      levels, resulted in the highest parent social validity ratings, and was selected
      as most preferred in treatment preference evaluations.

PMID- 22403465
TI  - Teaching children with autism to seek help when lost in public.
AB  - Children with autism may not develop safety skills (e.g., help-seeking behaviors)
      without explicit teaching. One potentially hazardous situation is when a child
      with autism becomes separated from caregivers in a retail establishment or other
      public setting. The purpose of this study was to evaluate a treatment package
      (rules, role playing, and praise) delivered in the natural environment for
      teaching 3 boys with autism to seek assistance from store employees when they
      became lost. Treatment was effective, and help-seeking behaviors generalized to
      untrained stores for all participants.

PMID- 22403466
TI  - Effects of behavioral skills training on parental treatment of children's food
      selectivity.
AB  - We used behavioral skills training to teach parents of 3 children with autism
      spectrum disorder and food selectivity to conduct a home-based treatment package
      that consisted of taste exposure, escape extinction, and fading. Parent
      performance following training improved during both taste sessions and probe
      meals and was reflected in increases in children's acceptance of bites and
      decreases in their disruptive behavior. Parents also reported that increases in
      diet variety were maintained at follow-up.

PMID- 22403467
TI  - Effects of text messaged self-monitoring on class attendance and punctuality of
      at-risk college student athletes.
AB  - This study examined the effects of text messaging class arrival to an academic
      counselor on the attendance and punctuality of 4 college student athletes. Each
      participant had a history of class tardiness and was considered to be at risk for
      academic failure. Class attendance and punctuality improved for all participants.

PMID- 22403468
TI  - The effects of exergaming on physical activity in a third-grade physical
      education class.
AB  - We compared the effects of exergaming and traditional physical education on
      physical activity among 4 active children who were not overweight and who had
      experience with the exergaming activities prior to the study. Results showed that
      exergaming produced substantially higher percentages of physical activity and
      opportunity to engage in physical activity. In addition, an evaluation of the
      exergaming equipment showed that exergaming stations were associated with
      differential levels of physical activity across participants.

PMID- 22403470
TI  - An experimental analysis of the effectiveness and sustainability of a Chinese
      tutoring package.
AB  - This experiment evaluated the effects of training tutors to use an instructional
      package to teach pronunciation and translation of the Chinese language. Tutors'
      correct use of the package increased from 68% of trials to 92% after training,
      and student correct pronunciation increased from 45% to 90%, with similar effects
      for translation. Continued use of the package, high social validity, and extended
      follow-up suggest that use of the package may be sustainable.

PMID- 22403472
TI  - The effects of high-preference problems on the completion of nonpreferred
      mathematics problems.
AB  - Failure to initiate and remain engaged in academic tasks can have long-lasting
      effects for students. In this study, we investigated the effects of high
      preference sequences on both digits correct per minute and latency to initiate
      nonpreferred mathematics problems for 3 students with emotional and behavioral
      disorders. We found that high-preference sequences had negligible positive
      effects on rate of problem completion but had larger effects on problem
      initiation. This study replicates and extends prior work on the effects of high
      preference sequences on mathematics problem initiation and completion.

PMID- 22403473
TI  - Asperisporium and Pantospora (Mycosphaerellaceae): epitypifications and
      phylogenetic placement.
AB  - The species-rich family Mycosphaerellaceae contains considerable morphological
      diversity and includes numerous anamorphic genera, many of which are economically
      important plant pathogens. Recent revisions and phylogenetic research have
      resulted in taxonomic instability. Ameliorating this problem requires
      phylogenetic placement of type species of key genera. We present an examination
      of the type species of the anamorphic Asperisporium and Pantospora. Cultures
      isolated from recent port interceptions were studied and described, and
      morphological studies were made of historical and new herbarium specimens. DNA
      sequence data from the ITS region and nLSU were generated from these type
      species, analysed phylogenetically, placed into an evolutionary context within
      Mycosphaerellaceae, and compared to existing phylogenies. Epitype specimens
      associated with living cultures and DNA sequence data are designated herein.
      Asperisporium caricae, the type of Asperisporium and cause of a leaf and fruit
      spot disease of papaya, is closely related to several species of Passalora
      including P. brachycarpa. The status of Asperisporium as a potential generic
      synonym of Passalora remains unclear. The monotypic genus Pantospora, typified by
      the synnematous Pantospora guazumae, is not included in Pseudocercospora sensu
      stricto or sensu lato. Rather, it represents a distinct lineage in the
      Mycosphaerellaceae in an unresolved position near Mycosphaerella microsora.

PMID- 22403474
TI  - Resolving the Diaporthe species occurring on soybean in Croatia.
AB  - Diaporthe (anamorph = Phomopsis) species are plant pathogens and endophytes on a
      wide range of hosts including economically important crops. At least four
      Diaporthe taxa occur on soybean and they are responsible for serious diseases and
      significant yield losses. Although several studies have extensively described the
      culture and morphological characters of these pathogens, their taxonomy has not
      been fully resolved. Diaporthe and Phomopsis isolates were obtained from soybean
      and other plant hosts throughout Croatia. Phylogenetic relationships were
      determined through analyses of partial translation elongation factor 1-alpha (EF1
      alpha) gene and ITS nrDNA sequence data. By combining morphological and molecular
      data, four species could be distinguished on soybeans in Croatia. Diaporthe
      phaseolorum is described in this study and its synonyms are discussed. Diaporthe
      phaseolorum var. caulivora is raised to species status and the name Diaporthe
      caulivora is introduced to accommodate it. A species previously known as
      Phomopsis sp. 9 from earlier studies on sunflower, grapevine, rooibos and
      hydrangea is reported for the first time on soybean, and is formally described as
      Diaporthe novem. The well-known soybean pathogen Phomopsis longicolla was also
      collected in the present study and was transferred to Diaporthe longicolla comb.
      nov. The presence of these species on herbaceous hosts raises once more the
      relevance of weeds as reservoirs for pathogens of economically important plants.

PMID- 22403475
TI  - Fungal pathogens of Proteaceae.
AB  - Species of Leucadendron, Leucospermum and Protea (Proteaceae) are in high demand
      for the international floriculture market due to their brightly coloured and
      textured flowers or bracts. Fungal pathogens, however, create a serious problem
      in cultivating flawless blooms. The aim of the present study was to characterise
      several of these pathogens using morphology, culture characteristics, and DNA
      sequence data of the rRNA-ITS and LSU genes. In some cases additional genes such
      as TEF 1-alpha and CHS were also sequenced. Based on the results of this study,
      several novel species and genera are described. Brunneosphaerella leaf blight is
      shown to be caused by three species, namely B. jonkershoekensis on Protea repens,
      B. nitidae sp. nov. on Protea nitida and B. protearum on a wide host range of
      Protea spp. (South Africa). Coniothyrium-like species associated with
      Coniothyrium leaf spot are allocated to other genera, namely Curreya grandicipis
      on Protea grandiceps, and Microsphaeropsis proteae on P. nitida (South Africa).
      Diaporthe leucospermi is described on Leucospermum sp. (Australia), and Diplodina
      microsperma newly reported on Protea sp. (New Zealand). Pyrenophora blight is
      caused by a novel species, Pyrenophora leucospermi, and not Drechslera biseptata
      or D. dematoidea as previously reported. Fusicladium proteae is described on
      Protea sp. (South Africa), Pestalotiopsis protearum on Leucospermum cuneiforme
      (Zimbabwe), Ramularia vizellae and R. stellenboschensis on Protea spp. (South
      Africa), and Teratosphaeria capensis on Protea spp. (Portugal, South Africa).
      Aureobasidium leaf spot is shown to be caused by two species, namely A. proteae
      comb. nov. on Protea spp. (South Africa), and A. leucospermi sp. nov. on
      Leucospermum spp. (Indonesia, Portugal, South Africa). Novel genera and species
      elucidated in this study include Gordonomyces mucovaginatus and Pseudopassalora
      gouriqua (hyphomycetes), and Xenoconiothyrium catenata (coelomycete), all on
      Protea spp. (South Africa).

PMID- 22403476
TI  - Waterborne Exophiala species causing disease in cold-blooded animals.
AB  - The majority of mesophilic waterborne species of the black yeast genus Exophiala
      (Chaetothyriales) belong to a single clade judging from SSU rDNA data. Most taxa
      are also found to cause cutaneous or disseminated infections in cold-blooded,
      water animals, occasionally reaching epidemic proportions. Hosts are mainly fish,
      frogs, toads, turtles or crabs, all sharing smooth, moist or mucous skins and
      waterborne or amphibian lifestyles; occasionally superficial infections in humans
      are noted. Cold-blooded animals with strictly terrestrial life styles, such as
      reptiles and birds are missing. It is concluded that animals with moist skins,
      i.e. those being waterborne and those possessing sweat glands, are more
      susceptible to black yeast infection. Melanin and the ability to assimilate
      alkylbenzenes are purported general virulence factors. Thermotolerance influences
      the choice of host. Exophiala species in ocean water mostly have maximum growth
      temperatures below 30  degrees C, whereas those able to grow until 33(-36) 
      degrees C are found in shallow waters and occasionally on humans. Tissue
      responses vary with the phylogenetic position of the host, the lower animals
      showing poor granulome formation. Species circumscriptions have been determined
      by multilocus analyses involving partial ITS, TEF1, BT2 and ACT1.

PMID- 22403477
TI  - Calonectria spp. causing leaf spot, crown and root rot of ornamental plants in
      Tunisia.
AB  - Calonectria spp. are important pathogens of ornamental plants in nurseries,
      especially in the Northern Hemisphere. They are commonly associated with a wide
      range of disease symptoms of roots, leaves and shoots. During a recent survey in
      Tunisia, a number of Calonectria spp. were isolated from tissues of ornamental
      plants showing symptoms of leaf spot, crown and root rot. The aim of this study
      was to identify these Calonectria spp. using morphological and DNA sequence
      comparisons. Two previously undescribed Calonectria spp., C. pseudomexicana sp.
      nov. and C. tunisiana sp. nov., were recognised. Calonectria mexicana and C.
      polizzii are newly reported for the African continent. Pathogenicity tests with
      all four Calonectria spp. showed that they are able to cause disease on seedlings
      of Callistemon spp., Dodonaea viscosa, Metrosideros spp. and Myrtus communis.

PMID- 22403478
TI  - Stem cankers on sunflower (Helianthus annuus) in Australia reveal a complex of
      pathogenic Diaporthe (Phomopsis) species.
AB  - The identification of Diaporthe (anamorph Phomopsis) species associated with stem
      canker of sunflower (Helianthus annuus) in Australia was studied using
      morphology, DNA sequence analysis and pathology. Phylogenetic analysis revealed
      three clades that did not correspond with known taxa, and these are believed to
      represent novel species. Diaporthe gulyae sp. nov. is described for isolates that
      caused a severe stem canker, specifically pale brown to dark brown, irregularly
      shaped lesions centred at the stem nodes with pith deterioration and mid-stem
      lodging. This pathogenicity of D. gulyae was confirmed by satisfying Koch's
      Postulates. These symptoms are almost identical to those of sunflower stem canker
      caused by D. helianthi that can cause yield reductions of up to 40 % in Europe
      and the USA, although it has not been found in Australia. We show that there has
      been broad misapplication of the name D. helianthi to many isolates of Diaporthe
      (Phomopsis) found causing, or associated with, stem cankers on sunflower. In
      GenBank, a number of isolates had been identified as D. helianthi, which were
      accommodated in several clades by molecular phylogenetic analysis. Two less
      damaging species, D. kochmanii sp. nov. and D. kongii sp. nov., are also
      described from cankers on sunflower in Australia.

PMID- 22403479
TI  - Reassessing Vermisporium (Amphisphaeriaceae), a genus of foliar pathogens of
      eucalypts.
AB  - The genus Vermisporium presently accommodates 13 species, 11 of which are
      associated with leaf spots of eucalypts in the Southern Hemisphere. Vermisporium
      is chiefly distinguished from Seimatosporium (Amphisphaeriaceae) on the basis of
      a short exogenous basal appendage, and the absence of a recognisable apical
      appendage. Due to the increasing importance of these species in native forests,
      and confusion pertaining to their taxonomy, a revision of the genus was
      undertaken based on fresh collections and dried herbarium specimens. Results from
      DNA sequence data analyses of the nrDNA-ITS and 28S nrRNA genes for species of
      Vermisporium indicated the genus to be a synonym of Seimatosporium. New
      combinations are introduced in Seimatosporium for several species: S. acutum, S.
      biseptatum, S. brevicentrum, S. obtusum, S. orbiculare, S. verrucisporum and S.
      walkeri. An updated key to all species occurring on eucalypts is also provided.

PMID- 22403480
TI  - The genera of Hyphomycetes - 2011 update.
AB  - This supplement to the taxonomic monograph The Genera of Hyphomycetes summarises
      information on 23 accepted new genera and c. 160 species described in 2011. These
      include three dematiaceous genera (Funbolia, Noosia, Pyrigemmula, all related to
      Dothideomycetes), a bulbil-producing genus, Spiroplana (Pleosporales), and two
      endophytic genera, the sterile Periglandula (Clavicipitaceae), and the hyaline,
      sympodial Micronematobotrys (Pyronemataceae). Slow-growing, morphologically
      reduced, darkly pigmented fungi continue to be the source of new taxa, including
      the new genus Atramixtia (Dothioraceae). Eight new genera of darkly pigmented
      chlamydospore-like anamorphs were described from marine or subtidal environments
      (Glomerulispora, Halozoon, Hiogispora, Matsusporium, Moheitospora, Moleospora,
      Moromyces), mostly associated with subclades of the Lulworthiales. Several genera
      that are morphologically similar to but phylogenetically distinct from genera of
      the Capnodiales (Pseudopassalora, Scleroramularia) were introduced, as well as
      segregates from the classical concepts of Alternaria (Sinomyces), Chalara and
      Phialophora (Brachyalara, Infundichalara, Lasiadelphia), and Paecilomyces
      (Purpureocillium for the former Paecilomyces lilacinus complex). In addition, in
      anticipation of the new nomenclatural rules, newly configured formerly-teleomorph
      genera were proposed as segregates from classical hyphomycete genera in the
      Hypocreales, namely Acremonium (Cosmospora), Fusarium (Cyanonectria,
      Dialonectria, Geejayessia, Macroconia, Stylonectria), and Volutella
      (Pseudonectria) and the Trichocomaceae, Eurotiales, Penicillium (Talaromyces for
      the former Penicillium subg. Biverticillium). Standardized generic mini-diagnoses
      are provided for the accepted new genera, along with details of distribution,
      substrates, numbers of new species and phylogenetic affinities within the
      Dikarya. GenBank accession numbers for ITS DNA-barcodes are provided where
      available. New information on generic concepts of previously recognised genera,
      phylogenetic relationships, and corrections of factual errors are also included.
      Only two newly described genera, Fecundostilbum and Utrechtiana, seem to be
      synonyms of previously described genera.

PMID- 22403481
TI  - Fungal Planet description sheets: 92-106.
AB  - Novel species of microfungi described in the present study include the following
      from Australia: Diaporthe ceratozamiae on Ceratozamia robusta, Seiridium banksiae
      on Banksia marginata, Phyllosticta hymenocallidicola on Hymenocallis littoralis,
      Phlogicylindrium uniforme on Eucalyptus cypellocarpa, Exosporium livistonae on
      Livistona benthamii and Coleophoma eucalyptorum on Eucalyptus piperita. Several
      species are also described from South Africa, namely: Phoma proteae, Pyrenochaeta
      protearum and Leptosphaeria proteicola on Protea spp., Phaeomoniella niveniae on
      Nivenia stokoei, Toxicocladosporium leucadendri on Leucadendron sp. and Scorias
      leucadendri on Leucadendron muirii. Other species include Myrmecridium phragmitis
      on Phragmites australis (Netherlands) and Camarographium carpini on Carpinus
      betulus (Russia). Furthermore, Pseudoidriella syzygii on Syzygium sp. represents
      a novel genus of hyphomycetes collected in Australia. Morphological and culture
      characteristics along with ITS DNA barcodes are provided for all taxa.

PMID- 22403482
TI  - Overcoming the effects of matrix interference in the measurement of urine protein
      analytes.
AB  - Using multiplex bead assays to measure urine proteins has a great potential for
      biomarker discovery, but substances in urine (the matrix) can interfere with
      assay measurements. By comparing the recovery of urine spiked with known
      quantities of several common analytes, this study demonstrated that the urine
      matrix variably interfered with the accurate measurement of low abundance
      proteins. Dilution of the urine permitted a more accurate measure of these
      proteins, equivalent to the standard dilution technique when the diluted analytes
      were above the limits of detection of the assay. Therefore, dilution can be used
      as an effective technique for over-coming urine matrix effects in urine
      immunoassays. These results may be applicable to other biological fluids in which
      matrix components interfere with assay performance.

PMID- 22403483
TI  - Detection of 1p19q deletion by real-time comparative quantitative PCR.
AB  - 1p/19q (1p and/or 19q) deletions are prognostic factors in oligodendroglial
      tumors (OT) and predict better survival after both chemotherapy and radiotherapy.
      While studying 1p/19q status as a potential variable within multivariate
      prognosis models for OT, we have frequently encountered unknown 1p/19q status
      within our glioma sample database due to lack of paired blood samples for loss of
      heterozygosity (LOH) assay and/or failure to perform fluorescence in situ
      hybridization (FISH). We realized that a 1p and 19q deletion assay that could be
      reliably performed solely on tumor DNA samples would allow us to fill in these
      molecular biology data "holes". We built recombinant DNA with fragments of the
      selected "marker" genes in 1p (E2F2, NOTCH2), and 19q (PLAUR) and "reference"
      genes (ERC2, SPOCK1, and SPAG16 ) and used it as quantification standard in real
      time PCR to gain absolute ratios of marker/reference gene copy numbers in tumor
      DNA samples, thus called comparative quantitative PCR (CQ-PCR). Using CQ-PCR, we
      identified 1p and/ or 19q deletions in majority of pure low-grade
      oligodenroglioma (OG) tumors (17/21, 81%), a large portion of anaplastic
      oligodendroglioma (AO) tumors (6/15, 47%), but rarely found in mixed
      oligoastrcytomas (OA) tumors (1/8, 13%). These data are consistent with results
      of LOH and FISH assays generally reported for these tumor types. In addition, 15
      out 18 samples showed concordant results between FISH and CQ-PCR. We conclude
      that CQ-PCR is a potential means to gain 1p/19q deletion information, which
      prognostic and predictive values of CQ-PCR-derived 1p/19q status will be
      determined in a future study.

PMID- 22403484
TI  - Delivering hydrophilic and hydrophobic chemotherapeutics simultaneously by
      magnetic mesoporous silica nanoparticles to inhibit cancer cells.
AB  - Using nanoparticles to deliver chemotherapeutics offers new opportunities for
      cancer therapy, but challenges still remain when they are used for the delivery
      of multiple drugs, especially for the synchronous delivery of hydrophilic and
      hydrophobic drugs in combination therapies. In this paper, we developed an
      approach to deliver hydrophilic-hydrophobic anticancer drug pairs by employing
      magnetic mesoporous silica nanoparticles (MMSNs). We prepared 50 nm-sized MMSNs
      with uniform pore size and evaluated their capability for the loading of two
      combinations of chemotherapeutics, namely doxorubicin-paclitaxel and doxorubicin
      rapamycin, by means of sequential adsorption from the aqueous solution of
      doxorubicin and nonaqueous solutions of paclitaxel or rapamycin. Experimental
      results showed that the present strategy successfully realized the co-loading of
      hydrophilic and hydrophobic drugs with high-loading content and widely tunable
      ratio range. We elaborate on the theory behind the molecular interaction between
      the silica hydroxyl groups and drug molecules, which underlie the controllable
      loading, and the subsequent release of the drug pairs. Then we demonstrate that
      the multidrug-loaded MMSNs could be easily internalized by A549 human pulmonary
      adenocarcinoma cells, and produce enhanced tumor cell apoptosis and growth
      inhibition as compared to single-drug loaded MMSNs. Our study thus realized
      simultaneous and dose-tunable delivery of hydrophilic and hydrophobic drugs,
      which were endowed with improved anticancer efficacy. This strategy could be
      readily extended to other chemotherapeutic combinations and might have clinically
      translatable significance.

PMID- 22403485
TI  - Targeted delivery of Tet1 peptide functionalized polymersomes to the rat cochlear
      nerve.
AB  - Polymersomes are nanosized vesicles formed from amphiphilic block copolymers, and
      have been identified as potential drug delivery vehicles to the inner ear. The
      aim of this study was to provide targeting to specific cells within the inner ear
      by functionalizing the polymersome surface with Tet1 peptide sequence. Tet1
      peptide specifically binds to the trisialoganglioside clostridial toxin receptor
      on neurons and was expected to target the polymersomes toward the cochlear nerve.
      The Tet1 functionalized PEG-b-PCL polymersomes were administered using routine
      drug delivery routes: transtympanic injection and cochleostomy. Delivery via
      cochleostomy of Tet1 functionalized polymersomes resulted in cochlear nerve
      targeting; in contrast this was not seen after transtympanic injection.

PMID- 22403486
TI  - In vitro and in vivo studies on gelatin-siloxane nanoparticles conjugated with
      SynB peptide to increase drug delivery to the brain.
AB  - BACKGROUND: Nanobiotechnology can provide more efficient tools for diagnosis,
      targeted and personalized therapy, and increase the chances of brain tumor
      treatment being successful. Use of nanoparticles is a promising strategy for
      overcoming the blood-brain barrier and delivering drugs to the brain. Gelatin
      siloxane (GS) nanoparticles modified with Tat peptide can enhance plasmid DNA
      transfection efficiency compared with a commercial reagent. METHODS: SynB-PEG-GS
      nanoparticles are membrane-penetrable, and can cross the blood-brain barrier and
      deliver a drug to its target site in the brain. The efficiency of delivery was
      investigated in vivo and in vitro using brain capillary endothelial cells, a
      cocultured blood-brain barrier model, and a normal mouse model. RESULTS: Our
      study demonstrated that both SynB-PEG-GS and PEG-GS nanoparticles had a spherical
      shape and an average diameter of 150-200 nm. It was shown by MTT assay that SynB
      PEG-GS nanoparticles had good biocompatibility with brain capillary endothelial
      cells. Cellular uptake by SynB-PEG-GS nanoparticles was higher than that for PEG
      GS nanoparticles for all incubation periods. The amount of SynB-PEG-GS
      nanoparticles crossing the cocultured blood-brain barrier model was significantly
      higher than that of PEG-GS nanoparticles at all time points measured (P < 0.05).
      In animal testing, SynB-PEG-GS nanoparticle levels in the brain were
      significantly higher than those of PEG-GS nanoparticles at all time points
      measured (P < 0.01). In contrast with localization in the brain, PEG-GS
      nanoparticle levels were significantly higher than those of SynB-PEG-GS
      nanoparticles (P < 0.01) in the liver. CONCLUSION: This study indicates that SynB
      PEG-GS nanoparticles have favorable properties with regard to morphology, size
      distribution, and toxicity. Moreover, the SynB-PEG-GS nanoparticles exhibited
      more efficient brain capillary endothelial cell uptake and improved crossing of
      the blood-brain barrier. Further, biodistribution studies of rhodamine-loaded
      nanoparticles demonstrated that modification with the SynB peptide could not only
      improve the ability of PEG-GS nanoparticles to evade capture in the
      reticuloendothelial system but also enhance their efficiency in crossing the
      blood-brain barrier.

PMID- 22403487
TI  - Nanomedicine: towards development of patient-friendly drug-delivery systems for
      oncological applications.
AB  - The focus on nanotechnology in cancer treatment and diagnosis has intensified due
      to the serious side effects caused by anticancer agents as a result of their
      cytotoxic actions on normal cells. This nonspecific action of chemotherapy has
      awakened a need for formulations capable of definitive targeting with enhanced
      tumor-killing. Nanooncology, the application of nanobiotechnology to the
      management of cancer, is currently the most important area of nanomedicine.
      Currently several nanomaterial-based drug-delivery systems are in vogue and
      several others are in various stages of development. Tumor-targeted drug-delivery
      systems are envisioned as magic bullets for cancer therapy and several groups are
      working globally for development of robust systems.

PMID- 22403488
TI  - Promising plasmid DNA vector based on APTES-modified silica nanoparticles.
AB  - Nanoparticles have an enormous potential for development in biomedical
      applications, such as gene or drug delivery. We developed and characterized
      aminopropyltriethoxysilane-functionalized silicon dioxide nanoparticles (APTES
      SiNPs) for gene therapy. Lipofectamine((r)) 2000, a commonly used agent, served
      as a contrast. We showed that APTES-SiNPs had a gene transfection efficiency
      almost equal to that of Lipofectamine 2000, but with lower cytotoxicity. Thus,
      these novel APTES-SiNPs can achieve highly efficient transfection of plasmid DNA,
      and to some extent reduce cytotoxicity, which might overcome the critical
      drawbacks in vivo of conventional carriers, such as viral vectors, organic
      polymers, and liposomes, and seem to be a promising nonviral gene therapy vector.

PMID- 22403489
TI  - Increased fibroblast functionality on CNN2-loaded titania nanotubes.
AB  - Infection and epithelial downgrowth are major problems associated with
      maxillofacial percutaneous implants. These complications are mainly due to the
      improper closure of the implant-skin interface. Therefore, designing a
      percutaneous implant that better promotes the formation of a stable soft tissue
      biologic seal around percutaneous sites is highly desirable. Additionally, the
      fibroblast has been proven to play an important role in the formation of biologic
      seals. In this study, titania nanotubes were filled with 11.2 kDa C-terminal CCN2
      (connective tissue growth factor) fragment, which could exert full CCN2 activity
      to increase the biological functionality of fibroblasts. This drug delivery
      system was fabricated on a titanium implant surface. CCN2 was loaded into
      anodized titania nanotubes using a simplified lyophilization method and the
      loading efficiency was approximately 80%. Then, the release kinetics of CCN2 from
      these nanotubes was investigated. Furthermore, the influence of CCN2-loaded
      titania nanotubes on fibroblast functionality was examined. The results revealed
      increased fibroblast adhesion at 0.25, 0.5, 1, 2, 4, and 24 hours, increased
      fibroblast viability over the course of 5 days, as well as enhanced actin
      cytoskeleton organization on CCN2-loaded titania nanotubes surfaces compared to
      uncoated, unmodified counterparts. Therefore, the results from this in vitro
      study demonstrate that CCN2-loaded titania nanotubes have the ability to increase
      fibroblast functionality and should be further studied as a method of promoting
      the formation of a stable soft tissue biologic seal around percutaneous sites.

PMID- 22403490
TI  - Nanoscale modification of porous gelatin scaffolds with chondroitin sulfate for
      corneal stromal tissue engineering.
AB  - Recent studies reflect the importance of using naturally occurring biopolymers as
      three-dimensional corneal keratocyte scaffolds and suggest that the porous
      structure of gelatin materials may play an important role in controlling nutrient
      uptake. In the current study, the authors further consider the application of
      carbodiimide cross-linked porous gelatin as an alternative to collagen for
      corneal stromal tissue engineering. The authors developed corneal keratocyte
      scaffolds by nanoscale modification of porous gelatin materials with chondroitin
      sulfate (CS) using carbodiimide chemistry. Scanning electron microscopy/energy
      dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy showed
      that the amount of covalently incorporated polysaccharide was significantly
      increased when the CS concentration was increased from 0% to 1.25% (w/v). In
      addition, as demonstrated by dimethylmethylene blue assays, the CS content in
      these samples was in the range of 0.078-0.149 nmol per 10 mg scaffold. When
      compared with their counterparts without CS treatment, various CS-modified porous
      gelatin membranes exhibited higher levels of water content, light transmittance,
      and amount of permeated nutrients but possessed lower Young's modulus and
      resistance against protease digestion. The hydrophilic and mechanical properties
      of scaffolds modified with 0.25% CS were comparable with those of native corneas.
      The samples from this group were biocompatible with the rabbit corneal
      keratocytes and showed enhanced proliferative and biosynthetic capacity of
      cultured cells. In summary, the authors found that the nanoscale-level
      modification has influence on the characteristics and cell-material interactions
      of CS-containing gelatin hydrogels. Porous membranes with a CS content of 0.112
      +/- 0.003 nmol per 10 mg scaffold may hold potential for use in corneal stromal
      tissue engineering.

PMID- 22403491
TI  - Improved oral bioavailability of poorly water-soluble indirubin by a
      supersaturatable self-microemulsifying drug delivery system.
AB  - BACKGROUND: Indirubin, isolated from the leaves of the Chinese herb Isatis
      tinctoria L, is a protein kinase inhibitor and promising antitumor agent.
      However, the poor water solubility of indirubin has limited its application. In
      this study, a supersaturatable self-microemulsifying drug delivery system (S
      SMEDDS) was developed to improve the oral bioavailability of indirubin. METHODS:
      A prototype S-SMEDDS was designed using solubility studies and phase diagram
      construction. Precipitation inhibitors were selected from hydrophilic polymers
      according to their crystallization-inhibiting capacity through in vitro
      precipitation tests. In vitro release of indirubin from S-SMEDDS was examined to
      investigate its likely release behavior in vivo. The in vivo bioavailability of
      indirubin from S-SMEDDS and from SMEDDS was compared in rats. RESULTS: The
      prototype formulation of S-SMEDDS comprised MaisineTM 35-1:Cremophor((r))
      EL:Transcutol((r)) P (15:40:45, w/w/w). Polyvinylpyrrolidone K17, a hydrophilic
      polymer, was used as a precipitation inhibitor based on its better
      crystallization-inhibiting capacity compared with polyethylene glycol 4000 and
      hydroxypropyl methylcellulose. In vitro release analysis showed more rapid drug
      release from S-SMEDDS than from SMEDDS. In vivo bioavailability analysis in rats
      indicated that improved oral absorption was achieved and that the relative
      bioavailability of S-SMEDDS was 129.5% compared with SMEDDS. CONCLUSION: The
      novel S-SMEDDS developed in this study increased the dissolution rate and
      improved the oral bioavailability of indirubin in rats. The results suggest that
      S-SMEDDS is a superior means of oral delivery of indirubin.

PMID- 22403492
TI  - Degradable gene delivery systems based on Pluronics-modified low-molecular-weight
      polyethylenimine: preparation, characterization, intracellular trafficking, and
      cellular distribution.
AB  - BACKGROUND: Cationic copolymers consisting of polycations linked to nonionic
      amphiphilic block polymers have been evaluated as nonviral gene delivery systems,
      and a large number of different polymers and copolymers of linear, branched, and
      dendrimeric architectures have been tested in terms of their suitability and
      efficacy for in vitro and in vivo transfection. However, the discovery of new
      potent materials still largely relies on empiric approaches rather than a
      rational design. The authors investigated the relationship between the polymers'
      structures and their biological performance, including DNA compaction, toxicity,
      transfection efficiency, and the effect of cellular uptake. METHODS: This article
      reports the synthesis and characterization of a series of cationic copolymers
      obtained by grafting polyethyleneimine with nonionic amphiphilic surfactant
      polyether-Pluronic((r)) consisting of hydrophilic ethylene oxide and hydrophobic
      propylene oxide blocks. Transgene expression, cytotoxicity, localization of
      plasmids, and cellular uptake of these copolymers were evaluated following in
      vitro transfection of HeLa cell lines with various individual components of the
      copolymers. RESULTS: Pluronics can exhibit biological activity including effects
      on enhancing DNA cellular uptake, nuclear translocation, and gene expression. The
      Pluronics with a higher hydrophilic-lipophilic balance value lead to homogeneous
      distribution in the cytoplasm; those with a lower hydrophilic-lipophilic balance
      value prefer to localize in the nucleus. CONCLUSION: This Pluronic
      polyethyleneimine system may be worth exploring as components in the cationic
      copolymers as the DNA or small interfering RNA/microRNA delivery system in the
      near future.

PMID- 22403493
TI  - The role of optical coherence tomography in coronary intervention.
AB  - Optical coherence tomography (OCT) is an optical analog of intravascular
      ultrasound (IVUS) that can be used to examine the coronary arteries and has 10
      fold higher resolution than IVUS. Based on polarization properties, OCT can
      differentiate tissue characteristics (fibrous, calcified, or lipid-rich plaque)
      and identify thin-cap fibroatheroma. Because of the strong attenuation of light
      by blood, OCT systems required the removal of blood during OCT examinations. A
      recently developed frequency-domain OCT system has a faster frame rate and
      pullback speed, making the OCT procedure more user-friendly and not requiring
      proximal balloon occlusion. During percutaneous coronary intervention (PCI), OCT
      can provide detailed information (dissection, tissue prolapse, thrombi, and
      incomplete stent apposition [ISA]). At follow-up examinations after stent
      implantation, stent strut coverage and ISA can be assessed. Several OCT studies
      have demonstrated delayed neointimal coverage following drug-eluting stent (DES)
      implantation vs. bare metal stent (BMS) placement. While newer DESs promote more
      favorable vascular healing, the clinical implications remain unknown. Recent OCT
      studies have provided insights into restenotic tissue characteristics; DES
      restenotic morphologies differ from those with BMSs. OCT is a novel, promising
      imaging modality; with more in-depth assessments of its use, it may impact
      clinical outcomes in patients with symptomatic coronary artery disease.

PMID- 22403494
TI  - Albumin for end-stage liver disease.
AB  - Albumin has been widely used in patients with cirrhosis in an attempt to improve
      circulatory and renal functions. The benefits of albumin infusions in preventing
      the deterioration in renal function associated with large-volume paracentesis,
      spontaneous bacterial peritonitis, and established hepatorenal syndrome in
      conjunction with a vasoconstrictor are well established. While some of these
      indications are supported by the results of randomized studies, others are based
      only on clinical experience and have not been proved in prospective studies. The
      paucity of well-designed trials, the high cost of albumin, the lack of a clear
      cut survival benefit, and fear of transmitting unknown infections make the use of
      albumin controversial. The recent development of the molecular adsorbent
      recirculating system, an albumin dialysis, is an example of the capacity of
      albumin to act by mechanisms other than its oncotic effect. Efforts should be
      made to define the indications for albumin use, the dose required, and predictors
      of response, so that patients gain the maximum benefit from its administration.

PMID- 22403495
TI  - Update on endoscopic management of main pancreatic duct stones in chronic
      calcific pancreatitis.
AB  - Pancreatic duct stones are a common complication during the natural course of
      chronic pancreatitis and often contribute to additional pain and pancreatitis.
      Abdominal pain, one of the major symptoms of chronic pancreatitis, is believed to
      be caused in part by obstruction of the pancreatic duct system (by stones or
      strictures) resulting in increasing intraductal pressure and parenchymal
      ischemia. Pancreatic stones can be managed by surgery, endoscopy, or
      extracorporeal shock wave lithotripsy. In this review, updated management of
      pancreatic duct stones is discussed.

PMID- 22403496
TI  - Optimization of stent deployment by intravascular ultrasound.
AB  - Intravascular ultrasound (IVUS) is a useful diagnostic method that provides
      valuable information in addition to angiography regarding the coronary vessel
      lumen, dimensions, plaque burden, and characteristics. The major use of IVUS in
      coronary intervention is to guide interventional strategies and assess optimal
      stent deployment. Since the introduction of the drug-eluting stent (DES),
      concerns about restenosis have decreased. However, high-risk lesion subsets are
      being routinely treated with DESs, and the incidence of suboptimal results after
      stent deployment, such as stent underexpansion, incomplete stent apposition, edge
      dissection, geographic miss, and the risk of stent thrombosis, have
      correspondingly increased. Thus, optimization of stent deployment under IVUS
      guidance may be clinically important. In this review, we focus on the potential
      role of IVUS in stent optimization during percutaneous coronary intervention and
      its clinical benefits.

PMID- 22403497
TI  - An emerging diabetes mellitus diagnosis modality: HbA(1c).

PMID- 22403498
TI  - Validity of glycated hemoglobin in screening and diagnosing type 2 diabetes
      mellitus in Chinese subjects.
AB  - BACKGROUND/AIMS: The application of glycated hemoglobin (HbA(1c)) for the
      diagnosis of diabetes is currently under extensive discussion. In this study, we
      explored the validity of using HbA(1c) as a screening and diagnostic test in
      Chinese subjects recruited in Nanjing, China. METHODS: In total, 497 subjects
      (361 men and 136 women) with fasting plasma glucose (PG) >= 5.6 mmol/L were
      recruited to undergo the oral glucose tolerance test (OGTT) and HbA(1c) test.
      Plasma lipid, uric acid, and blood pressure were also measured. RESULTS: Using a
      receiver operating characteristic curve, the optimal cutoff point of HbA(1c)
      related to diabetes diagnosed by the OGTT was 6.3%, with a sensitivity and
      specificity of 79.6% and 82.2%, respectively, and the area under the curve was
      0.87 (95% confidence interval, 0.83 to 0.92). A HbA(1c) level of 6.5% had a
      sensitivity and specificity of 62.7% and 93.5%, respectively. When comparing the
      HbA(1c) >= 6.5% or OGTT methods for diagnosing diabetes, the former group had
      significantly higher HbA(1c) levels and lower levels of fasting and 2-hour PG
      than the latter group. No significant difference was observed in the other
      metabolism indexes between the two groups. CONCLUSIONS: Our results suggest that
      HbA(1c) >= 6.5% has reasonably good specificity for diagnosing diabetes in
      Chinese subjects, which is in concordance with the American Diabetes Association
      recommendations.

PMID- 22403499
TI  - Risk factors of cryptogenic hepatocellular carcinoma in patients with low body
      mass index or without metabolic syndrome.
AB  - BACKGROUND/AIMS: Many patients are diagnosed with cryptogenic hepatocellular
      carcinoma (HCC) without metabolic syndrome (MS). We investigated the risk factors
      for cryptogenic HCC in patients with a low body mass index (BMI) or without MS.
      METHODS: Thirty-six patients were diagnosed with cryptogenic HCC over a 10-year
      period at a tertiary research hospital. Data including BMI score and risk factors
      for MS were analyzed retrospectively. Patients with fewer than two risk factors
      for MS (n = 16) were compared with those with two or more risk factors (n = 20).
      Patients with high BMI (>= 23 kg/m(2), n = 20) were also compared with those with
      lower BMI (n = 16). RESULTS: Patients with fewer than two risk factors for MS
      were significantly more likely to smoke and be hepatitis B surface antibodies
      (anti-HBs)-positive vs. patients with two or more risk factors. However, only
      smoking was statistically significant on multivariate analysis. Peaks of BMI were
      observed in two regions. Lower BMI was significantly associated with the presence
      of anti-HBs compared with high BMI, although this association was not
      statistically significant on multivariate analysis. CONCLUSIONS: Smoking is a
      potential risk factor for cryptogenic HCC in patients without MS. Remote
      hepatitis B virus infection may be a risk factor for cryptogenic HCC in patients
      without MS or with a low BMI.

PMID- 22403500
TI  - Normalization of negative T-wave on electrocardiography and right ventricular
      dysfunction in patients with an acute pulmonary embolism.
AB  - BACKGROUND/AIMS: Right ventricular dysfunction (RVD) is associated with poor
      prognosis in patients with acute pulmonary embolism (APE). Echocardiography and
      computed tomography (CT)-angiography may be difficult to perform in a serial
      follow up, unlike electrocardiography (ECG). Many ECG findings specific for APE
      have been reported, and many studies have found that negative T-waves (NTW) in
      precordial leads are most frequently observed in patients with APE. We analyzed
      serial changes in precordial NTW to detect RVD and predict the recovery of RVD in
      patients with APE. METHODS: We examined 81 consecutive patients diagnosed with
      APE using CT-angiography or echocardiography. ECG, transthoracic
      echocardiography, and laboratory tests were performed within 24 hours of
      admission, and daily ECG follow-up was performed. Precordial NTWs were defined by
      the new development of pointed and symmetrical inverted T-waves in at least three
      leads. Recovery of NTW was defined as flattening or upright inverted T-waves in
      more than two leads. RESULTS: Of the 81 patients with APE, 52 (64%) had RVD
      according to echocardiography. Among the patients with RVD, 33 (63%) showed
      precordial NTW. The multivariate logistic regression analysis revealed that NTW
      was the strongest independent predictor for RVD (odds ratio, 22.8; 95% confidence
      interval, 2.4 to 221.4; p = 0.007). Time to normalization of NTW was associated
      with improvement of RVD on echocardiography (r = 0.84, p < 0.01). CONCLUSIONS:
      Precordial NTW was a reliable finding to identify RVD in patients with APE.
      Improvements in RVD can be predicted by normalizing precordial NTW.

PMID- 22403501
TI  - Positive result in the early passive phase of the tilt-table test: a predictor of
      neurocardiogenic syncope in young men.
AB  - BACKGROUND/AIMS: This study elucidated the prognostic factors for
      neurocardiogenic syncope in males in their late teens and early twenties.
      METHODS: Tilt-table testing (TTT) was performed on 665 males (age range, 17 to 27
      years) following the Italian protocol. The subjects were tilted head-up at a 70
      degrees  angle on a table for 30 minutes during the passive phase. If the passive
      phase was negative, the subjects were given sublingual nitroglycerin and tilted
      to the same angle for 20 minutes during the drug-provocation phase. The subjects
      with positive results were followed without medication. We analyzed factors
      related to the recurrence rate of syncope. RESULTS: Of 305 subjects (45.8%) with
      positive results, 223 (age range, 18 to 26 years) were followed for 12 months.
      The frequency of previous syncopal episodes >= 4 (p = 0.001) and a positive
      result during the passive phase (p = 0.022) were significantly related to a high
      recurrence rate. A positive result during the early passive phase (<= 12 minutes)
      was significantly related to a higher recurrence rate than was that during the
      late passive phase (> 12 minutes; p = 0.011). CONCLUSIONS: A positive result
      during the early passive phase of TTT and frequent previous syncopal episodes
      were prognostic factors for neurocardiogenic syncope in men in their late teens
      and early twenties.

PMID- 22403502
TI  - Associations among body mass index, insulin resistance, and pancreatic beta-cell
      function in Korean patients with new-onset type 2 diabetes.
AB  - BACKGROUND/AIMS: We investigated the associations among body mass index (BMI),
      insulin resistance, and beta-cell function in Korean patients newly presenting
      with type 2 diabetes. METHODS: In total, 132 patients with new-onset type 2
      diabetes mellitus were investigated. A standard 75-g oral glucose tolerance test
      was performed, and the indices of insulin secretion and insulin resistance were
      calculated. RESULTS: A higher BMI was associated with higher homeostasis model
      assessment values for insulin resistance (HOMA-IR), homeostasis model assessment
      of beta-cell function (HOMA-beta), and insulinogenic index as well as lower
      levels of insulin sensitivity index composite (ISI(comp)) and disposition index
      (DI). In multiple regression models, BMI had independent positive associations
      with HOMA-IR, ISI(comp), and HOMA-beta and inverse associations with the DI.
      CONCLUSIONS: Our results showed that BMI had independent positive associations
      with indices of insulin resistance and an inverse association with beta-cell
      function adjusted for insulin resistance in Korean patients newly presenting with
      type 2 diabetes.

PMID- 22403504
TI  - Effects of add-on therapy with NDC-052, an extract from Magnoliae Flos, in adult
      asthmatic patients receiving inhaled corticosteroids.
AB  - BACKGROUND/AIMS: There is a need for new anti-asthmatic medications with fewer
      side effects. NDC-052, an extract of the medicinal herb Magnoliae flos, which has
      a long history of clinical use, was recently found to have anti-inflammatory
      effects. Herein, we evaluated the effects of NDC-052 as an add-on therapy in
      patients with mild to moderate asthma using inhaled corticosteroids (ICS).
      METHODS: In a non-comparative, multi-center trial, 148 patients taking ICS
      received NDC-052 for eight weeks. We evaluated their forced expiratory volume in
      one second (FEV1), morning and evening peak expiratory flow rate (AM and PM
      PEFR), AM/PM asthma symptom scores, visual analogue symptom (VAS) scores, night
      time wakening, frequency of short-acting beta2-agonist usage, and adverse events.
      RESULTS: After eight weeks, both AM and PM PEFRs were significantly improved.
      Asthma symptom scores, VAS scores, the frequency of nights without awakening, and
      the frequency of beta2-agonist use were also reduced. Most of the adverse drug
      reactions were mild and resolved spontaneously. CONCLUSIONS: The addition of NDC
      052 to ICS had a beneficial effect on asthma control in patients with mild to
      moderate asthma, with good tolerability and fewer side effects. Further studies
      are necessary to evaluate the effects of NDC-052 in patients with severe and/or
      refractory asthma.

PMID- 22403503
TI  - Feasibility of non-TBI conditioning with busulfan and fludarabine for allogeneic
      stem cell transplantation in lymphoid malignancy.
AB  - BACKGROUND/AIMS: This retrospective study evaluated the transplantation outcomes
      of patients with adult lymphoid malignancies who received chemotherapy-based
      conditioning with busulfan and fludarabine (BuFlu) and busulfan and
      cyclophosphamide (BuCy2). METHODS: Thirty-eight patients (34 with acute
      lymphoblastic leukemia and 4 with lymphoblastic lymphoma) were included in the
      current study. The conditioning regimen was BuCy2 for 14 patients and BuFlu for
      the remaining 24 patients. Eight and 13 patients were high risk disease in the
      BuCy2 and BuFlu groups, respectively. RESULTS: The cumulative incidence of grade
      II-IV acute graft-versus-host disease (GVHD) was 56.5% and 55.2% and that of
      extensive chronic GVHD 17.0% and 55.6% (p = 0.018) for the BuFlu and BuCy2
      groups, respectively. The 3-year relapse rate was 27.8% and 31.4% and 3-year
      overall survival 34.3% and 46.8% for the BuFlu and BuCy2 groups, respectively.
      Treatment-related mortality (TRM) was significantly lower in the BuFlu group
      (16.9%) than in the BuCy2 group (57.1%, p = 0.010). In multivariate analyses, the
      BuFlu regimen was identified as an independent favorable risk factor for TRM
      (hazard ratio [HR], 0.036; p = 0.017) and extensive chronic GVHD (HR, 0.168; p =
      0.034). CONCLUSIONS: Our BuFlu regimen would appear to be an acceptable
      conditioning option for lymphoid malignancies, including high-risk diseases. It
      was safely administered with a lower TRM rate than BuCy2 conditioning.

PMID- 22403505
TI  - Ewing's sarcoma of the lesser sac masquerading as a pancreatic tumor.
AB  - Extraosseous Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) is an
      uncommon, aggressive, and malignant tumor with a poor patient outcome. Its
      occurrence in the lesser sac is a rare event and to the best of our knowledge,
      has not been previously described. The present case was clinically and
      radiologically misdiagnosed as a pancreatic tumor/gastrointestinal stromal tumor.
      Histopathology revealed a tumor with "small round cells" that were positive for
      CD99, confirming the diagnosis of ES/PNET. This report highlights the importance
      of considering Ewing's sarcoma in the differential diagnosis of intraabdominal,
      extraintestinal masses.

PMID- 22403506
TI  - Development of Brugada syndrome following photodynamic therapy in a patient with
      cholangiocarcinoma.
AB  - Brugada syndrome can be unmasked by several conditions including a febrile state,
      marked leukocytosis, and electrolyte disturbances. Herein, we describe a 62-year
      old man with cholangiocarcinoma in the first reported case of Brugada syndrome
      onset following photodynamic therapy.

PMID- 22403507
TI  - Spontaneous non-traumatic stress fractures in bilateral femoral shafts in a
      patient treated with bisphosphonates.
AB  - Bisphosphonates are potent inhibitors of bone resorption and widely used to treat
      osteoporosis. Extensive studies have shown that therapy with bisphosphonates
      improves bone density and decreases fracture risk. However, concerns have been
      raised about potential over-suppression of bone turnover during long-term use of
      bisphosphonates, resulting in increased susceptibility to and delayed healing of
      non-spinal fractures. We report a patient who sustained non-traumatic stress
      fractures in bilateral femoral shafts with delayed healing after long-term
      bisphosphonate therapy. She underwent open reduction and surgical internal
      fixation. Although bisphosphonates effectively prevent vertebral fractures, and
      their safety has been tested in randomized trials, we must emphasize the need for
      awareness of the possibility that long-term suppression of bone turnover with
      bisphosphonates may eventually lead to an accumulation of fatigue-induced damage
      and adverse skeletal effects such as delayed fracture healing.

PMID- 22403508
TI  - Adenocarcinoma arising in a duplication of the cecum.
AB  - Intestinal duplications are rare developmental abnormalities that may occur
      anywhere in the gastrointestinal tract. The possibility of a malignant change
      occurring in these duplications is very low. We present a case of adenocarcinoma
      arising in a duplication of the cecum. A 41-year-old male patient was admitted
      because of a palpable abdominal mass. Abdominal computed tomography revealed a 6
      cm, peripheral wall-enhanced, round, cystic mass in the cecal area. Excision of
      the mesenteric mass and a right hemicolectomy was performed. Upon histologic
      examination, the patient was diagnosed with adenocarcinoma arising in a
      duplication of the cecum.

PMID- 22403509
TI  - Stress-induced cardiomyopathy presenting as ventricular tachycardia.

PMID- 22403510
TI  - Primary pulmonary plasmacytoma presenting as multiple lung nodules.

PMID- 22403511
TI  - Induction of donor-specific tolerance: is this achievable?

PMID- 22403512
TI  - A case of therapy-related acute myeloid leukemia following 5-fluorouracil
      chemotherapy.

PMID- 22403513
TI  - A tulip-shaped gastric carcinoid tumor.

PMID- 22403514
TI  - Biopsy-proven type 1 renal tubular acidosis in a patient with metabolic acidosis.

PMID- 22403515
TI  - Inactivation of bacteria using dc corona discharge: role of ions and humidity.
AB  - Here we present the results of an experimental study of the effect of ions
      produced in a dc corona discharge on inactivation of bacteria on the surface of
      agarose gel. Both positive and negative corona discharges in various gases at
      different humidities were studied. The measurements in air, O(2), N(2), Ar and He
      mixtures show that there is no inactivation in pure N(2), pure O(2) and an N(2)
      H(2)O mixture. The best results were achieved in the case of direct treatment,
      when discharge was ignited in oxygen and water-containing mixtures. We show that
      neither UV radiation, ozone or H(2)O(2) nor other neutral active species alone
      produced by corona have an effect on bacteria viability. It is shown that the
      main role of charged particles may be related to the faster transport of active
      peroxide species-cluster ions OH(-)(H(2)O)(n) and H(3)O(+)(H(2)O)(n). The
      efficiency of these radicals is much higher than that of the oxygen radicals and
      ions (including [Formula: see text] and O(3)) and that of nitrogen and argon
      ions.

PMID- 22403518
TI  - The EUROCET Network: Support for Coding, Vigilance and Surveillance.
AB  - BACKGROUND: In the last years, there have been increasing concerns about the
      safety and traceability of human tissues and cells in Europe. In order to
      regulate this part of medical practice, the European Commission issued 3
      directives between 2004 and 2006 and endorsed EUROCET to support member states in
      fulfilling some of their obligations.  MATHODS: EUROCET created a connection with
      the European Union (EU) Competent Authorities (CAs) and set up a website where
      lists of the CAs, the authorized Tissue Establishments (TEs) and the activity
      data are published and updated. Moreover, EUROCET is involved within the
      Vigilance and Surveillance of Substances of Human Origin (SOHO V&S) project,
      aiming to support the EU member states in the establishment of vigilance and
      surveillance systems for tissues and cells. EUROCET is also working with EU
      stakeholders to develop a common coding system concerning donation and products. 
      RESULTS: There are 33 countries in EUROCET and 57 CAs. 3,974 TEs are recorded:
      1,108 for tissues, 1,480 for haematopoietic progenitor cells and 1,386 for
      assisted reproduction. On the website, it is possible to find the 2010 activity
      data report.  CONCLUSION: Based on its cooperation with the CAs, EUROCET
      represents them in the European network. Nowadays, the EU member states can rely
      on a web portal and database in order to put the tissue and cell directives into
      practice.

PMID- 22403516
TI  - More on the cohort-component model of population projection in the context of
      HIV/AIDS: A Leslie matrix representation and new estimates.
AB  - This article presents an extension of the cohort-component model of population
      projection (CCMPP) first formulated by Heuveline (2003) that is capable of
      modeling a population affected by HIV. Heuveline proposes a maximum likelihood
      approach to estimate the age profile of HIV incidence that produced the HIV
      epidemics in East Africa during the 1990s. We extend this work by developing the
      Leslie matrix representation of the CCMPP, which greatly facilitates the
      implementation of the model for parameter estimation and projection. The Leslie
      matrix also contains information about the stable tendencies of the corresponding
      population, such as the stable age distribution and time to stability. Another
      contribution of this work is that we update the sources of data used to estimate
      the parameters, and use these data to estimate a modified version of the CCMPP
      that includes (estimated) parameters governing the survival experience of the
      infected population. A further application of the model to a small population
      with high HIV prevalence in rural South Africa is presented as an additional
      demonstration. This work lays the foundation for development of more robust and
      flexible Bayesian estimation methods that will greatly enhance the utility of
      this and similar models.

PMID- 22403519
TI  - A Q Fever Outbreak in the Netherlands: Consequences for Tissue Banking.
AB  - BACKGROUND: Emerging infectious diseases can compromise the safety of tissues for
      transplantations. A recent outbreak of Q fever, a zoonosis caused by the
      bacterium Coxiella burnetii, in the Netherlands compelled the Dutch tissue banks
      to assess the risk of Q fever transmission through tissue transplantation in
      order to maintain optimal safety.  MATHODS: This article describes the systematic
      approach that was followed in the Netherlands. This approach included a review of
      the literature, a qualitative risk assessment, expert opinion gathering and
      investigations for specific strategies that can help to maintain the balance
      between tissue safety and availability.  RESULTS: This resulted in a specific
      donor selection policy and in development of further research to fill in gaps in
      knowledge about Q fever in tissue transplantation.  CONCLUSION: The strategy
      described in this article may be useful for tissue bankers facing similar
      outbreaks of emerging infections or may be useful for development of future
      guidelines or assessment strategies for tissue banking.

PMID- 22403520
TI  - Validation of the Serological Testing for Anti-HIV-1/2, Anti-HCV, HBsAg, and Anti
      HBc from Post-mortem Blood on the Siemens-BEP-III Automatic System.
AB  - BACKGROUND: Some properties of blood are modified post mortem. These
      modifications might give false-negative or false-positive results in infectious
      disease testing. Most CE-marked test equipment for infectious serology testing is
      not validated for testing post-mortal blood. Validation, however, is obligatory,
      if the results are used for the release of tissues for transplantation.  MATHODS:
      Samples of pre- and post-mortem sera were obtained from 20 cornea donors, and the
      results were compared for anti-HIV-1/2, anti-HCV, HBsAg, and anti-HBc on the
      Siemens-BEP-III Automatic System. Negative post-mortem sera were spiked with
      standard sera (PEI anti-HCV IgG, PEI HBsAg ad 1000 standard, anti-HBc IgG (WHO)
      NIBSC 95/522, PEI anti-HIV-IV) in concentrations which give low- and high
      positive results for the respective marker.  RESULTS: All pre-mortem sera were
      negative for all markers. None of the post-mortem samples was false-positive.
      None of the spiked postmortem samples was false-negative. Technical errors
      occurred during the validation process but could be detected and eliminated.
      Serum samples should be centrifuged immediately after collection, and it must be
      taken into account that post-mortem serum could rarely lead to blockage of
      pipetting systems due to clotting phenomena.  CONCLUSION: There is no indication
      that post-mortem samples give false-negative or false-positve results with the
      test system and test kits used. The procedure described might serve as a model
      for validating other test kits on post-mortem samples.

PMID- 22403521
TI  - An Analysis of Bone Donor Deferral Rates in Scotland - a 6-Year Study.
AB  - BACKGROUND: The Scottish National Blood Transfusion Service (SNBTS) is the main
      provider of tissues in Scotland. Tissue collection programmes were established in
      the mid-1990s, and the range of tissues collected has increased progressively
      over the years.  MATHODS: Whilst the majority of tissues are obtained from
      cadaveric donations, bone is collected only from living donors who are usually
      patients undergoing primary hip replacement surgery (surgical donors). The bone
      is collected in an operating theatre, and, once stored, no further processing
      takes place prior to issue. Bone that fails for any reason (quality, microbiology
      or virological nonnegative result) is discarded.  RESULTS: The deferral rate
      amongst live surgical bone donors in Scotland is around 65%, and it has been
      slowly and progressively rising from around 55% over the past few years. This
      needed investigated, particularly because comparisons with blood donors show that
      the deferral rate amongst bone donors is more than double that of first-time
      blood donors (29.7%). Our processes and systems are standardised, and our cohort
      of bone bank nurses have all been similarly trained and competency assessed.
      Moreover our data collection was done in a uniform fashion. It was therefore
      possible to conduct a 6-year audit on bone donor deferrals. It was found that a
      history of transfusion (16%), history of malignancy (18%) and bone quality (26%)
      were the main reasons for bone donor deferrals, accounting for 60% of all
      deferrals.  CONCLUSIONS: When these are taken into account, the residual deferral
      rates become very similar numerically to blood donors. It is important to note
      however that there are significant differences between the blood and bone donor
      cohorts. This study also highlighted some of deferral reasons. Particularly
      malignancy is a cause of significant numbers of deferrals, and the evidence of
      transmissibility of malignancy through bone donation is not strong. More robust
      risk assessments should be undertaken prior to implementing deferral conditions.

PMID- 22403522
TI  - Determination of Residual Antibiotics in Cryopreserved Heart Valve Allografts.
AB  - INTRODUCTION: Cardiovascular allografts are systematically incubated in
      antibiotics for their decontamination, and the antibiotics are removed before
      allograft implantation. We studied the occurrence of antibiotic residues in
      allograft valves.  MATHODS: 12 experimental allografts were analyzed in this
      study. The concentration of the residual antibiotics was determined by high
      performance liquid chromatography and the results were expressed as microgram per
      gram of allograft tissue.  RESULTS: The initial analysis showed that only
      vancomycin HCl and lincomycin HCl were retained in the allograft, whereas no
      traces of polymyxin B sulfate were detected in the tissue samples. Furthermore,
      the values found for the antibiotic residues in the extracted solution from the
      allografts were similar to the initial results: Vancomycin and lincomycin were
      detected in very low concentrations and no polymyxin B residues were observed.
      According to the World Health Organization (WHO), the maximum daily doses for
      vancomycin, lincomycin and pol-ymyxin B are 2.0, 1.8 and 0.4 g, respectively. The
      thresholds for reporting degradation products are 0.05% for vancomycin and
      lincomycin and 0.1% for polymyxin B. The residual values for the two detected
      antibiotics were largely below 0.05%.  CONCLUSIONS: Antibiotic residues in the
      allograft valves do not present any risk for their recipients. Increased
      allograft resistance to infections is probably due to the retention of
      antibiotics in the tissue.

PMID- 22403523
TI  - Impact of Hypothermia upon Chondrocyte Viability and Cartilage Matrix
      Permeability after 1 Month of Refrigerated Storage.
AB  - BACKGROUND: The purpose of this research was to assess the extracellular matrix
      and chondrocytes of articular cartilage during refrigerated storage and to
      determine whether changes could be detected in the time frame that cartilage is
      stored for clinical use.  MATHODS: Porcine cartilage was stored as either
      bisected femoral heads with bone attached or plugs without the underlying bone in
      culture medium with fetal bovine serum for 1 month at 4  degrees C. Metabolic
      activity was tested using a resazurin reduction method on intact tissue and
      viable cell recovery after enzymatic tissue digestion at each time point.
      Cartilage plug permeability was evaluated by measuring electrical conductivity. 
      RESULTS: Storage in culture medium provided good cartilage viability and
      metabolic function for 7 days; however, significant changes were observed in
      femoral heads (p < 0.05). All mean chondrocyte assessment values were <30% of
      fresh controls at 28 days. Cartilage plugs tended to perform better after 7 days
      of storage than the femoral heads and retained significantly higher metabolic
      activity (mean = 94.5% vs. 70.5%; p < 0.05). Cartilage plugs demonstrated
      consistent changes in electrical conductivity after 28 days of storage (p <
      0.05).  CONCLUSION: Refrigerated storage of cartilage results in both loss of
      chondrocyte viability and matrix permeability.

PMID- 22403524
TI  - Neural correlates of dynamically evolving interpersonal ties predict prosocial
      behavior.
AB  - There is a growing interest for the determinants of human choice behavior in
      social settings. Upon initial contact, investment choices in social settings can
      be inherently risky, as the degree to which the other person will reciprocate is
      unknown. Nevertheless, people have been shown to exhibit prosocial behavior even
      in one-shot laboratory settings where all interaction has been taken away. A
      logical step has been to link such behavior to trait empathy-related
      neurobiological networks. However, as a social interaction unfolds, the degree of
      uncertainty with respect to the expected payoff of choice behavior may change as
      a function of the interaction. Here we attempt to capture this factor. We show
      that the interpersonal tie one develops with another person during interaction -
      rather than trait empathy - motivates investment in a public good that is shared
      with an anonymous interaction partner. We examined how individual differences in
      trait empathy and interpersonal ties modulate neural responses to imposed
      monetary sharing. After, but not before interaction in a public good game,
      sharing prompted activation of neural systems associated with reward (striatum),
      empathy (anterior insular cortex and anterior cingulate cortex) as well as
      altruism, and social significance [posterior superior temporal sulcus (pSTS)].
      Although these activations could be linked to both empathy and interpersonal
      ties, only tie-related pSTS activation predicted prosocial behavior during
      subsequent interaction, suggesting a neural substrate for keeping track of social
      relevance.

PMID- 22403525
TI  - Distinction between Externally vs. Internally Guided Decision-Making: Operational
      Differences, Meta-Analytical Comparisons and Their Theoretical Implications.
AB  - Most experimental studies of decision-making have specifically examined
      situations in which a single less-predictable correct answer exists (externally
      guided decision-making under uncertainty). Along with such externally guided
      decision-making, there are instances of decision-making in which no correct
      answer based on external circumstances is available for the subject (internally
      guided decision-making). Such decisions are usually made in the context of moral
      decision-making as well as in preference judgment, where the answer depends on
      the subject's own, i.e., internal, preferences rather than on external, i.e.,
      circumstantial, criteria. The neuronal and psychological mechanisms that allow
      guidance of decisions based on more internally oriented criteria in the absence
      of external ones remain unclear. This study was undertaken to compare decision
      making of these two kinds empirically and theoretically. First, we reviewed
      studies of decision-making to clarify experimental-operational differences
      between externally guided and internally guided decision-making. Second, using
      multi-level kernel density analysis, a whole-brain-based quantitative meta
      analysis of neuroimaging studies was performed. Our meta-analysis revealed that
      the neural network used predominantly for internally guided decision-making
      differs from that for externally guided decision-making under uncertainty. This
      result suggests that studying only externally guided decision-making under
      uncertainty is insufficient to account for decision-making processes in the
      brain. Finally, based on the review and results of the meta-analysis, we discuss
      the differences and relations between decision-making of these two types in terms
      of their operational, neuronal, and theoretical characteristics.

PMID- 22403526
TI  - A Role for K2P Channels in the Operation of Somatosensory Nociceptors.
AB  - The ability to sense mechanical, thermal, and chemical stimuli is critical to
      normal physiology and the perception of pain. Contact with noxious stimuli
      triggers a complex series of events that initiate innate protective mechanisms
      designed to minimize or avoid injury. Extreme temperatures, mechanical stress,
      and chemical irritants are detected by specific ion channels and receptors
      clustered on the terminals of nociceptive sensory nerve fibers and transduced
      into electrical information. Propagation of these signals, from distant sites in
      the body to the spinal cord and the higher processing centers of the brain, is
      also orchestrated by distinct groups of ion channels. Since their identification
      in 1995, evidence has emerged to support roles for K2P channels at each step
      along this pathway, as receptors for physiological and noxious stimuli, and as
      determinants of nociceptor excitability and conductivity. In addition, the many
      subtypes of K2P channels expressed in somatosensory neurons are also implicated
      in mediating the effects of volatile, general anesthetics on the central and
      peripheral nervous systems. Here, I offer a critical review of the existing data
      supporting these attributes of K2P channel function and discuss how diverse
      regulatory mechanisms that control the activity of K2P channels act to govern the
      operation of nociceptors.

PMID- 22403527
TI  - On the evolution of memory: a time for clocks.
AB  - Evolutionarily, what was the earliest engram? Biology has evolved to encode
      representations of past events, and in neuroscience, we are attempting to link
      experience-dependent changes in molecular signaling with cellular processes that
      ultimately lead to behavioral output. The theory of evolution has guided
      biological research for decades, and since phylogenetically conserved mechanisms
      drive circadian rhythms, these processes may serve as common predecessors
      underlying more complex behavioral phenotypes. For example, the cAMP/MAPK/CREB
      cascade is interwoven with the clock to trigger circadian output, and is also
      known to affect memory formation. Time-of-day dependent changes have been
      observed in long-term potentiation (LTP) within the suprachiasmatic nucleus and
      hippocampus, along with light-induced circadian phase resetting and fear
      conditioning behaviors. Together this suggests during evolution, similar
      processes underlying metaplasticity in more simple circuits may have been
      redeployed in higher-order brain regions. Therefore, this notion predicts a model
      that LTP and metaplasticity may exist in neural circuits of other species,
      through phylogenetically conserved pathways, leading to several testable
      hypotheses.

PMID- 22403528
TI  - Epigenetic regulation of axon and dendrite growth.
AB  - Neuroregenerative therapies for central nervous system (CNS) injury,
      neurodegenerative disease, or stroke require axons of damaged neurons to grow and
      re-innervate their targets. However, mature mammalian CNS neurons do not
      regenerate their axons, limiting recovery in these diseases. Although neurons'
      intrinsic capacity for axon growth may depend in part on the panoply of expressed
      transcription factors, epigenetic factors such as the accessibility of DNA and
      organization of chromatin are required for downstream genes to be transcribed.
      Thus, a potential approach to overcoming regenerative failure focuses on the
      epigenetic mechanisms regulating regenerative gene expression in the CNS. Here we
      review molecular mechanisms regulating the epigenetic state of DNA through
      chromatin modifications, their implications for regulating axon and dendrite
      growth, and important new directions for this field of study.

PMID- 22403529
TI  - Ontogeny of neural circuits underlying spatial memory in the rat.
AB  - Spatial memory is a well-characterized psychological function in both humans and
      rodents. The combined computations of a network of systems including place cells
      in the hippocampus, grid cells in the medial entorhinal cortex and head direction
      cells found in numerous structures in the brain have been suggested to form the
      neural instantiation of the cognitive map as first described by Tolman in 1948.
      However, while our understanding of the neural mechanisms underlying spatial
      representations in adults is relatively sophisticated, we know substantially less
      about how this network develops in young animals. In this article we briefly
      review studies examining the developmental timescale that these systems follow.
      Electrophysiological recordings from very young rats show that directional
      information is at adult levels at the outset of navigational experience. The
      systems supporting allocentric memory, however, take longer to mature. This is
      consistent with behavioral studies of young rats which show that spatial memory
      based on head direction develops very early but that allocentric spatial memory
      takes longer to mature. We go on to report new data demonstrating that memory for
      associations between objects and their spatial locations is slower to develop
      than memory for objects alone. This is again consistent with previous reports
      suggesting that adult like spatial representations have a protracted development
      in rats and also suggests that the systems involved in processing non-spatial
      stimuli come online earlier.

PMID- 22403530
TI  - The insular cortex controls food preferences independently of taste receptor
      signaling.
AB  - The insular cortex (IC) contains the primary sensory cortex for oral
      chemosensation including gustation, and its integrity is required for appropriate
      control of feeding behavior. However, it remains unknown whether the role of this
      brain area in food selection relies on the presence of peripheral taste input.
      Using multielectrode recordings, we found that the responses of populations of
      neurons in the IC of freely licking, sweet-blind Trpm5(-/-) mice are modulated by
      the rewarding postingestive effects of sucrose. FOS immunoreactivity analyses
      revealed that these responses are restricted to the dorsal insula. Furthermore,
      bilateral lesions in this area abolished taste-independent preferences for
      sucrose that can be conditioned in these Trpm5(-/-) animals while preserving
      their ability to detect sucrose. Overall, these findings demonstrate that, even
      in the absence of peripheral taste input, IC regulates food choices based on
      postingestive signals.

PMID- 22403531
TI  - Social categories shape the neural representation of emotion: evidence from a
      visual face adaptation task.
AB  - A number of recent behavioral studies have shown that emotional expressions are
      differently perceived depending on the race of a face, and that perception of
      race cues is influenced by emotional expressions. However, neural processes
      related to the perception of invariant cues that indicate the identity of a face
      (such as race) are often described to proceed independently of processes related
      to the perception of cues that can vary over time (such as emotion). Using a
      visual face adaptation paradigm, we tested whether these behavioral interactions
      between emotion and race also reflect interdependent neural representation of
      emotion and race. We compared visual emotion aftereffects when the adapting face
      and ambiguous test face differed in race or not. Emotion aftereffects were much
      smaller in different race (DR) trials than same race (SR) trials, indicating that
      the neural representation of a facial expression is significantly different
      depending on whether the emotional face is black or white. It thus seems that
      invariable cues such as race interact with variable face cues such as emotion not
      just at a response level, but also at the level of perception and neural
      representation.

PMID- 22403532
TI  - Preventive role of social interaction for cocaine conditioned place preference:
      correlation with FosB/DeltaFosB and pCREB expression in rat mesocorticolimbic
      areas.
AB  - The worsening of drug abuse by drug-associated social interaction is a well
      studied phenomenon. In contrast, the molecular mechanisms of the beneficial
      effect of social interaction, if offered as a mutually exclusive choice to drugs
      of abuse, are under-investigated. In a rat place preference conditioning (CPP)
      paradigm, four 15 min episodes of social interaction with a gender- and weight
      matched male early-adult conspecific inhibited cocaine-induced reinstatement of
      cocaine CPP, a model of relapse. These protective effects of social interaction
      were paralleled by a reduced activation, as assessed by Zif268 expression, in
      brain areas known to play pivotal roles in drug-seeking behavior. Here we show
      that social interaction during extinction of cocaine CPP also reduced cocaine-CPP
      stimulated FosB expression in the nucleus accumbens shell and core. In addition,
      social interaction during cocaine CPP extinction increased pCREB (cAMP response
      element binding protein) expression in the nucleus accumbens shell and the
      cingulate cortex area 1 (Cg1). Our results show that FosB and pCREB may be
      implicated in the protective effect of social interaction against cocaine-induced
      reinstatement of CPP. Thus, social interaction, if offered in a context that is
      clearly distinct from the previously drug-associated one, may profoundly inhibit
      relapse to cocaine addiction.

PMID- 22403533
TI  - Binocular rivalry alternations and their relation to visual adaptation.
AB  - When different stimuli are presented dichoptically, perception alternates between
      the two in a stochastic manner. After a long-lasting and rigorous debate, there
      is growing consensus that this phenomenon, known as binocular rivalry (BR), is
      the result of a dynamic competition occurring at multiple levels of the visual
      hierarchy. The role of low- and high-level adaptation mechanisms in controlling
      these perceptual alternations has been a key issue in the rivalry literature.
      Both types of adaptation are dispersed throughout the visual system and have an
      equally influential, or even causal, role in determining perception. Such an
      explanation of BR is also in accordance with the relationship between the latter
      and attention. However, an overall explanation of this intriguing perceptual
      phenomenon needs to also include noise as an equally fundamental process involved
      in the stochastic resonance of perceptual bistability.

PMID- 22403535
TI  - Sensory augmentation for the blind.
AB  - Common navigational aids used by blind travelers during large-scale navigation
      divert attention away from important cues of the immediate environment (i.e.,
      approaching vehicles). Sensory augmentation devices, relying on principles
      similar to those at work in sensory substitution, can potentially bypass the
      bottleneck of attention through sub-cognitive implementation of a set of rules
      coupling motor actions with sensory stimulation. We provide a late blind subject
      with a vibrotactile belt that continually signals the direction of magnetic
      north. The subject completed a set of behavioral tests before and after an
      extended training period. The tests were complemented by questionnaires and
      interviews. This newly supplied information improved performance on different
      time scales. In a pointing task we demonstrate an instant improvement of
      performance based on the signal provided by the device. Furthermore, the signal
      was helpful in relevant daily tasks, often complicated for the blind, such as
      keeping a direction over longer distances or taking shortcuts in familiar
      environments. A homing task with an additional attentional load demonstrated a
      significant improvement after training. The subject found the directional
      information highly expedient for the adjustment of his inner maps of familiar
      environments and describes an increase in his feeling of security when exploring
      unfamiliar environments with the belt. The results give evidence for a firm
      integration of the newly supplied signals into the behavior of this late blind
      subject with better navigational performance and more courageous behavior in
      unfamiliar environments. Most importantly, the complementary information provided
      by the belt lead to a positive emotional impact with enhanced feeling of
      security. The present experimental approach demonstrates the positive potential
      of sensory augmentation devices for the help of handicapped people.

PMID- 22403536
TI  - Effects of meditation experience on functional connectivity of distributed brain
      networks.
AB  - This study sought to examine the effect of meditation experience on brain
      networks underlying cognitive actions employed during contemplative practice. In
      a previous study, we proposed a basic model of naturalistic cognitive
      fluctuations that occur during the practice of focused attention meditation. This
      model specifies four intervals in a cognitive cycle: mind wandering (MW),
      awareness of MW, shifting of attention, and sustained attention. Using subjective
      input from experienced practitioners during meditation, we identified activity in
      salience network regions during awareness of MW and executive network regions
      during shifting and sustained attention. Brain regions associated with the
      default mode were active during MW. In the present study, we reasoned that
      repeated activation of attentional brain networks over years of practice may
      induce lasting functional connectivity changes within relevant circuits. To
      investigate this possibility, we created seeds representing the networks that
      were active during the four phases of the earlier study, and examined functional
      connectivity during the resting state in the same participants. Connectivity maps
      were then contrasted between participants with high vs. low meditation
      experience. Participants with more meditation experience exhibited increased
      connectivity within attentional networks, as well as between attentional regions
      and medial frontal regions. These neural relationships may be involved in the
      development of cognitive skills, such as maintaining attention and disengaging
      from distraction, that are often reported with meditation practice. Furthermore,
      because altered connectivity of brain regions in experienced meditators was
      observed in a non-meditative (resting) state, this may represent a transference
      of cognitive abilities "off the cushion" into daily life.

PMID- 22403534
TI  - Neocortical-hippocampal dynamics of working memory in healthy and diseased brain
      states based on functional connectivity.
AB  - Working memory (WM) is the ability to transiently maintain and manipulate
      internal representations beyond its external availability to the senses. This
      process is thought to support high level cognitive abilities and been shown to be
      strongly predictive of individual intelligence and reasoning abilities. While
      early models of WM have relied on a modular perspective of brain functioning,
      more recent evidence suggests that cognitive functions emerge from the
      interactions of multiple brain regions to generate large-scale networks. Here we
      will review the current research on functional connectivity of WM processes to
      highlight the critical role played by neural interactions in healthy and
      pathological brain states. Recent findings demonstrate that WM abilities are not
      determined solely by local brain activity, but also rely on the functional
      coupling of neocortical-hippocampal regions to support WM processes. Although the
      hippocampus has long been held to be important for long-term declarative memory,
      recent evidence suggests that the hippocampus may also be necessary to coordinate
      disparate cortical regions supporting the periodic reactivation of internal
      representations in WM. Furthermore, recent brain imaging studies using
      connectivity measures, have shown that changes in cortico-limbic interactions can
      be useful to characterize WM impairments observed in different neuropathological
      conditions. Recent advances in electrophysiological and neuroimaging techniques
      to model network activity has led to important insights into how neocortical and
      hippocampal regions support WM processes and how disruptions along this network
      can lead to the memory impairments commonly reported in many neuropathological
      populations.

PMID- 22403537
TI  - Network-based statistics for a community driven transparent publication process.
AB  - The current publishing system with its merits and pitfalls is a mending topic for
      debate among scientists of various disciplines. Editors and reviewers alike, both
      face difficult decisions about the judgment of new scientific findings.
      Increasing interdisciplinary themes and rapidly changing dynamics in method
      development of each field make it difficult to be an "expert" with regard to all
      issues of a certain paper. Although unintended, it is likely that
      misunderstandings, human biases, and even outright mistakes can play an
      unfortunate role in final verdicts. We propose a new community-driven publication
      process that is based on network statistics to make the review, publication, and
      scientific evaluation process more transparent.

PMID- 22403538
TI  - Tracking replicability as a method of post-publication open evaluation.
AB  - Recent reports have suggested that many published results are unreliable. To
      increase the reliability and accuracy of published papers, multiple changes have
      been proposed, such as changes in statistical methods. We support such reforms.
      However, we believe that the incentive structure of scientific publishing must
      change for such reforms to be successful. Under the current system, the quality
      of individual scientists is judged on the basis of their number of publications
      and citations, with journals similarly judged via numbers of citations. Neither
      of these measures takes into account the replicability of the published findings,
      as false or controversial results are often particularly widely cited. We propose
      tracking replications as a means of post-publication evaluation, both to help
      researchers identify reliable findings and to incentivize the publication of
      reliable results. Tracking replications requires a database linking published
      studies that replicate one another. As any such database is limited by the number
      of replication attempts published, we propose establishing an open-access journal
      dedicated to publishing replication attempts. Data quality of both the database
      and the affiliated journal would be ensured through a combination of crowd
      sourcing and peer review. As reports in the database are aggregated, ultimately
      it will be possible to calculate replicability scores, which may be used
      alongside citation counts to evaluate the quality of work published in individual
      journals. In this paper, we lay out a detailed description of how this system
      could be implemented, including mechanisms for compiling the information,
      ensuring data quality, and incentivizing the research community to participate.

PMID- 22403539
TI  - Combining collation and annotation efforts toward completion of the rat and mouse
      connectomes in BAMS.
AB  - Many different independently published neuroanatomical parcellation schemes
      (brain maps, nomenclatures, or atlases) can exist for a particular species,
      although one scheme (a standard scheme) is typically chosen for mapping
      neuroanatomical data in a particular study. This is problematic for building
      connection matrices (connectomes) because the terms used to name structures in
      different parcellation schemes differ widely and interrelationships are seldom
      defined. Therefore, data sets cannot be compared across studies that have been
      mapped on different neuroanatomical atlases without a reliable translation
      method. Because resliceable 3D brain models for relating systematically and
      topographically different parcellation schemes are still in the first phases of
      development, it is necessary to rely on qualitative comparisons between regions
      and tracts that are either inserted directly by neuroanatomists or trained
      annotators, or are extracted or inferred by collators from the available
      literature. To address these challenges, we developed a publicly available
      neuroinformatics system, the Brain Architecture Knowledge Management System
      (BAMS; http://brancusi.usc.edu/bkms). The structure and functionality of BAMS is
      briefly reviewed here, as an exemplar for constructing interrelated connectomes
      at different levels of the mammalian central nervous system organization. Next,
      the latest version of BAMS rat macroconnectome is presented because it is
      significantly more populated with the number of inserted connectivity reports
      exceeding a benchmark value (50,000), and because it is based on a different
      classification scheme. Finally, we discuss a general methodology and strategy for
      producing global connection matrices, starting with rigorous mapping of data,
      then inserting and annotating it, and ending with online generation of large
      scale connection matrices.

PMID- 22403541
TI  - Molecular Insights into the Local Anesthetic Receptor within Voltage-Gated Sodium
      Channels Using Hydroxylated Analogs of Mexiletine.
AB  - We previously showed that the beta-adrenoceptor modulators, clenbuterol and
      propranolol, directly blocked voltage-gated sodium channels, whereas salbutamol
      and nadolol did not (Desaphy et al., 2003), suggesting the presence of two
      hydroxyl groups on the aromatic moiety of the drugs as a molecular requisite for
      impeding sodium channel block. To verify such an hypothesis, we synthesized five
      new mexiletine analogs by adding one or two hydroxyl groups to the aryloxy moiety
      of the sodium channel blocker and tested these compounds on hNav1.4 channels
      expressed in HEK293 cells. Concentration-response relationships were constructed
      using 25-ms-long depolarizing pulses at -30 mV applied from an holding potential
      of -120 mV at 0.1 Hz (tonic block) and 10 Hz (use-dependent block) stimulation
      frequencies. The half-maximum inhibitory concentrations (IC(50)) were linearly
      correlated to drug lipophilicity: the less lipophilic the drug, minor was the
      block. The same compounds were also tested on F1586C and Y1593C hNav1.4 channel
      mutants, to gain further information on the molecular interactions of mexiletine
      with its receptor within the sodium channel pore. In particular, replacement of
      Phe1586 and Tyr1593 by non-aromatic cysteine residues may help in the
      understanding of the role of pi-pi or pi-cation interactions in mexiletine
      binding. Alteration of tonic block suggests that the aryloxy moiety of mexiletine
      may interact either directly or indirectly with Phe1586 in the closed sodium
      channel to produce low-affinity binding block, and that this interaction depends
      on the electrostatic potential of the drug aromatic tail. Alteration of use
      dependent block suggests that addition of hydroxyl groups to the aryloxy moiety
      may modify high-affinity binding of the drug amine terminal to Phe1586 through
      cooperativity between the two pharmacophores, this effect being mainly related to
      drug lipophilicity. Mutation of Tyr1593 further impaired such cooperativity. In
      conclusion, these results confirm our former hypothesis by showing that the
      presence of hydroxyl groups to the aryloxy moiety of mexiletine greatly reduced
      sodium channel block, and provide molecular insights into the intimate
      interaction of local anesthetics with their receptor.

PMID- 22403540
TI  - Brain glycogen-new perspectives on its metabolic function and regulation at the
      subcellular level.
AB  - Glycogen is a complex glucose polymer found in a variety of tissues, including
      brain, where it is localized primarily in astrocytes. The small quantity found in
      brain compared to e.g., liver has led to the understanding that brain glycogen is
      merely used during hypoglycemia or ischemia. In this review evidence is brought
      forward highlighting what has been an emerging understanding in brain energy
      metabolism: that glycogen is more than just a convenient way to store energy for
      use in emergencies-it is a highly dynamic molecule with versatile implications in
      brain function, i.e., synaptic activity and memory formation. In line with the
      great spatiotemporal complexity of the brain and thereof derived focus on the
      basis for ensuring the availability of the right amount of energy at the right
      time and place, we here encourage a closer look into the molecular and
      subcellular mechanisms underlying glycogen metabolism. Based on (1) the
      compartmentation of the interconnected second messenger pathways controlling
      glycogen metabolism (calcium and cAMP), (2) alterations in the subcellular
      location of glycogen-associated enzymes and proteins induced by the metabolic
      status and (3) a sequential component in the intermolecular mechanisms of
      glycogen metabolism, we suggest that glycogen metabolism in astrocytes is
      compartmentalized at the subcellular level. As a consequence, the meaning and
      importance of conventional terms used to describe glycogen metabolism (e.g.,
      turnover) is challenged. Overall, this review represents an overview of
      contemporary knowledge about brain glycogen and its metabolism and function.
      However, it also has a sharp focus on what we do not know, which is perhaps even
      more important for the future quest of uncovering the roles of glycogen in brain
      physiology and pathology.

PMID- 22403542
TI  - Promotion of Myelopoiesis in Myelosuppressed Mice by Ganoderma lucidum
      Polysaccharides.
AB  - Our previous studies demonstrated that Ganoderma lucidum polysaccharides (Gl-PS)
      exhibit potent immunomodulating effects. Immunomodulation plays an important role
      in hematopoiesis. To investigate the possible mechanism by which Gl-PS promote
      myelopoiesis during myelosuppression induced by cyclophosphamide, mice were
      injected intraperitoneally (i.p.) once daily with 2.5 mg/kg of Gl-PS for 10 days
      and were treated i.p. once daily with cyclophosphamide (100 mg/kg) on days 2
      through 4. In the present study in vivo and in vitro, we find that Gl-PS
      selectively bind to bone marrow stromal cells, stimulate the secretion of
      hematopoietic growth factors, and enhance the clonogenic activities of
      hematopoietic and stromal cells to promote hematopoiesis in myelosuppressed mice.

PMID- 22403543
TI  - Therapeutic Potential of Moringa oleifera Leaves in Chronic Hyperglycemia and
      Dyslipidemia: A Review.
AB  - Moringa oleifera (M. oleifera) is an angiosperm plant, native of the Indian
      subcontinent, where its various parts have been utilized throughout history as
      food and medicine. It is now cultivated in all tropical and sub-tropical regions
      of the world. The nutritional, prophylactic, and therapeutic virtues of this
      plant are being extolled on the Internet. Dietary consumption of its part is
      therein promoted as a strategy of personal health preservation and self
      medication in various diseases. The enthusiasm for the health benefits of M.
      oleifera is in dire contrast with the scarcity of strong experimental and
      clinical evidence supporting them. Fortunately, the chasm is slowly being filled.
      In this article, I review current scientific data on the corrective potential of
      M. oleifera leaves in chronic hyperglycemia and dyslipidemia, as symptoms of
      diabetes and cardiovascular disease (CVD) risk. Reported studies in experimental
      animals and humans, although limited in number and variable in design, seem
      concordant in their support for this potential. However, before M. oleifera leaf
      formulations can be recommended as medication in the prevention or treatment of
      diabetes and CVD, it is necessary that the scientific basis of their efficacy,
      the therapeutic modalities of their administration and their possible side
      effects be more rigorously determined.

PMID- 22403544
TI  - Ginsenosides as Anticancer Agents: In vitro and in vivo Activities, Structure
      Activity Relationships, and Molecular Mechanisms of Action.
AB  - Conventional chemotherapeutic agents are often toxic not only to tumor cells but
      also to normal cells, limiting their therapeutic use in the clinic. Novel natural
      product anticancer compounds present an attractive alternative to synthetic
      compounds, based on their favorable safety and efficacy profiles. Several pre
      clinical and clinical studies have demonstrated the anticancer potential of Panax
      ginseng, a widely used traditional Chinese medicine. The anti-tumor efficacy of
      ginseng is attributed mainly to the presence of saponins, known as ginsenosides.
      In this review, we focus on how ginsenosides exert their anticancer effects by
      modulation of diverse signaling pathways, including regulation of cell
      proliferation mediators (CDKs and cyclins), growth factors (c-myc, EGFR, and
      vascular endothelial growth factor), tumor suppressors (p53 and p21), oncogenes
      (MDM2), cell death mediators (Bcl-2, Bcl-xL, XIAP, caspases, and death
      receptors), inflammatory response molecules (NF-kappaB and COX-2), and protein
      kinases (JNK, Akt, and AMP-activated protein kinase). We also discuss the
      structure-activity relationship of various ginsenosides and their potentials in
      the treatment of various human cancers. In summary, recent advances in the
      discovery and evaluation of ginsenosides as cancer therapeutic agents support
      further pre-clinical and clinical development of these agents for the treatment
      of primary and metastatic tumors.

PMID- 22403545
TI  - Primary phagocytosis of neurons by inflamed microglia: potential roles in
      neurodegeneration.
AB  - Microglial phagocytosis of dead or dying neurons can be beneficial by preventing
      the release of damaging and/or pro-inflammatory intracellular components.
      However, there is now evidence that under certain conditions, such as
      inflammation, microglia can also phagocytose viable neurons, thus executing their
      death. Such phagocytic cell death may result from exposure of phosphatidylserine
      (PS) or other eat-me signals on otherwise viable neurons as a result of
      physiological activation or sub-toxic insult, and neuronal phagocytosis by
      activated microglia. In this review, we discuss the mechanisms of phagocytic cell
      death and its potential roles in Alzheimer's Disease, Parkinson's Disease, and
      Frontotemporal Dementia.

PMID- 22403546
TI  - Annexin A1 N-terminal derived Peptide ac2-26 exerts chemokinetic effects on human
      neutrophils.
AB  - It is postulated that peptides derived from the N-terminal region of Annexin A1,
      a glucocorticoid-regulated 37-kDa protein, could act as biomimetics of the parent
      protein. However, recent evidence, amongst which the ability to interact with
      distinct receptors other then that described for Annexin A1, suggest that these
      peptides might fulfill other functions at variance to those reported for the
      parent protein. Here we tested the ability of peptide Ac2-26 to induce chemotaxis
      of human neutrophils, showing that this peptide can elicit responses comparable
      to those produced by the canonical activator formyl-Met-Leu-Phe (or FMLP).
      However, whilst disruption of the chemical gradient abolished the FMLP response,
      addition of peptide Ac2-26 in the top well of the chemotaxis chamber did not
      affect (10 MUM) or augmented (at 30 MUM) the neutrophil locomotion to the bottom
      well, as elicited by 10 MUM peptide Ac2-26. Intriguingly, the sole addition of
      peptide Ac2-26 in the top wells produced a marked migration of neutrophils. A
      similar behavior was observed when human primary monocytes were used. Thus,
      peptide Ac2-26 is a genuine chemokinetic agent toward human blood leukocytes.
      Neutralization strategies indicated that engagement of either the GPCR termed
      FPR1 or its cognate receptor FPR2/ALX was sufficient to sustain peptide Ac2-26
      induced neutrophil migration. Similarly, application of pharmacological
      inhibitors showed that cell locomotion to peptide Ac2-26 was mediated primarily
      by the ERK, but not the JNK and p38 pathways. In conclusion, we report here novel
      in vitro properties for peptide Ac2-26, promoting neutrophil and monocyte
      chemokinesis; a process that may contribute to accelerate the resolution phase of
      inflammation. We postulate that the generation of Annexin A1 N-terminal peptides
      at the site of inflammation may expedite the egress of migrated leukocytes thus
      promoting the return to homeostasis.

PMID- 22403548
TI  - Integrated central-autonomic multifractal complexity in the heart rate
      variability of healthy humans.
AB  - PURPOSE OF STUDY: The aim of this study was to characterize the central-autonomic
      interaction underlying the multifractality in heart rate variability (HRV) of
      healthy humans. MATERIALS AND METHODS: Eleven young healthy subjects participated
      in two separate ~40 min experimental sessions, one in supine (SUP) and one in,
      head-up-tilt (HUT), upright (UPR) body positions. Surface scalp
      electroencephalography (EEG) and electrocardiogram (ECG) were collected and
      fractal correlation of brain and heart rate data was analyzed based on the idea
      of relative multifractality. The fractal correlation was further examined with
      the EEG, HRV spectral measures using linear regression of two variables and
      principal component analysis (PCA) to find clues for the physiological processing
      underlying the central influence in fractal HRV. RESULTS: We report evidence of a
      central-autonomic fractal correlation (CAFC) where the HRV multifractal
      complexity varies significantly with the fractal correlation between the heart
      rate and brain data (P = 0.003). The linear regression shows significant
      correlation between CAFC measure and EEG Beta band spectral component (P = 0.01
      for SUP and P = 0.002 for UPR positions). There is significant correlation
      between CAFC measure and HRV LF component in the SUP position (P = 0.04), whereas
      the correlation with the HRV HF component approaches significance (P = 0.07). The
      correlation between CAFC measure and HRV spectral measures in the UPR position is
      weak. The PCA results confirm these findings and further imply multiple
      physiological processes underlying CAFC, highlighting the importance of the EEG
      Alpha, Beta band, and the HRV LF, HF spectral measures in the supine position.
      DISCUSSION AND CONCLUSION: The findings of this work can be summarized into three
      points: (i) Similar fractal characteristics exist in the brain and heart rate
      fluctuation and the change toward stronger fractal correlation implies the change
      toward more complex HRV multifractality. (ii) CAFC is likely contributed by
      multiple physiological mechanisms, with its central elements mainly derived from
      the EEG Alpha, Beta band dynamics. (iii) The CAFC in SUP and UPR positions is
      qualitatively different, with a more predominant central influence in the fractal
      HRV of the UPR position.

PMID- 22403547
TI  - Regulation of sirtuin function by posttranslational modifications.
AB  - Sirtuins are homologs of the yeast silencing information regulator 2 protein, an
      NAD(+)-dependent (histone) deacetylase. In mammals seven different sirtuins,
      SIRT1-7, have been identified, which share a common catalytic core domain but
      possess distinct N- and C-terminal extensions. This core domain elicits NAD(+)
      dependent deacetylase and in some cases also ADP-ribosyltransferase,
      demalonylase, and desuccinylase activities. Sirtuins have been implicated in key
      cellular processes, including cell survival, autophagy, apoptosis, gene
      transcription, DNA repair, stress response, and genome stability. In addition
      some sirtuins are associated with disease, including cancer and
      neurodegeneration. These findings suggest strongly that sirtuins are tightly
      controlled and potentially responsive to different signal transduction pathways.
      Here, we review the posttranslational regulation mechanisms of mammalian sirtuins
      and discuss their relevance regarding the physiological processes, with which the
      different sirtuins are associated. The available data suggest that the N- and C
      terminal extensions are the targets of posttranslational modifications (PTM) that
      can affect the functions of sirtuins. Mechanistically this can be explained by
      the interaction of these extensions with the catalytic core domain, which appears
      to be controlled by PTM at least in some cases. In contrast little is known about
      PTM and regulation of the catalytic domain itself. Together these findings point
      to key regulatory roles of the N- and C-terminal extensions in controlling
      sirtuin functions, thus connecting these regulators to different signaling
      pathways.

PMID- 22403549
TI  - Protective Effects of Quercetin on Rat Pial Microvascular Changes during
      Transient Bilateral Common Carotid Artery Occlusion and Reperfusion.
AB  - The aim of this study was to assess the in vivo effects of quercetin on pial
      microvascular responses during transient bilateral common carotid artery
      occlusion (BCCAO) and reperfusion. Rat pial microcirculation was visualized by
      fluorescence microscopy through a closed cranial window. Pial arterioles were
      classified in five orders of branchings. Capillaries were assigned order 0, the
      smallest arterioles order 1, and the largest ones order 5. In ischemic rats, 30
      min BCCAO and 60 min reperfusion caused arteriolar diameter decrease (by 14.5 +/-
      3.3% of baseline in order 2), microvascular leakage [0.47 +/- 0.04, normalized
      gray levels (NGL)], leukocyte adhesion in venules (9 +/- 2/100 MUm venular
      length, v.l./30 s), and reduction of capillary perfusion (by 40 +/- 7% of
      baseline). Moreover, at the end of BCCAO and reperfusion there was a significant
      increase in reactive oxygen species (ROS) formation when compared with baseline.
      Quercetin highest dose determined dilation in all arteriolar orders (by 40 +/- 4%
      of baseline in order 2) and prevented microvascular permeability (0.15 +/- 0.02
      NGL), leukocyte adhesion (3 +/- 1/100 MUm v.l./30 s) as well as ROS formation,
      while capillary perfusion was protected. Inhibition of endothelial nitric oxide
      synthase (NOS) prior to quercetin reduced arteriolar dilation (order 2 diameter
      increase by 10.3 +/- 2.5% of baseline) and caused permeability increase (0.29 +/-
      0.03 NGL); inhibition of neuronal NOS or inducible NOS did not affect quercetin
      induced effects. Inhibition of guanylyl cyclase prior to quercetin reversed the
      quercetin's effects on pial arteriolar diameter and leakage. In conclusion,
      quercetin was able to protect pial microcirculation from ischemia-reperfusion
      damage inducing arteriolar dilation likely by nitric oxide release. Moreover,
      quercetin scavenger activity blunted ROS formation preserving the blood-brain
      barrier integrity.

PMID- 22403550
TI  - Association of Basal hyperglucagonemia with impaired glucagon counterregulation
      in type 1 diabetes.
AB  - Glucagon counterregulation (GCR) protects against hypoglycemia, but is impaired
      in type 1 diabetes (T1DM). A model-based analysis of in vivo animal data predicts
      that the GCR defects are linked to basal hyperglucagonemia. To test this
      hypothesis we studied the relationship between basal glucagon (BasG) and the GCR
      response to hypoglycemia in 29 hyperinsulinemic clamps in T1DM patients. Glucose
      levels were stabilized in euglycemia and then steadily lowered to 50 mg/dL.
      Glucagon was measured before induction of hypoglycemia and at 10 min intervals
      after glucose reached levels below 70 mg/dL. GCR was assessed by CumG, the
      cumulative glucagon levels above basal; MaxG, the maximum glucagon response; and
      RIG, the relative increase in glucagon over basal. Analysis of the results was
      performed with our mathematical model of GCR. The model describes interactions
      between islet peptides and glucose, reproduces the normal GCR axis and its
      impairment in diabetes. It was used to identify a control mechanism consistent
      with the observed link between BasG and GCR. Analysis of the clinical data showed
      that higher BasG was associated with lower GCR response. In particular, CumG and
      RIG correlated negatively with BasG (r = -0.46, p = 0.012 and r = -0.74, p <
      0.0001 respectively) and MaxG increased linearly with BasG at a rate less than
      unity (p < 0.001). Consistent with these results was a model of GCR in which the
      secretion of glucagon has two components. The first is under (auto) feedback
      control and drives a pulsatile GCR and the second is feedback independent (basal
      secretion) and its increase suppresses the GCR. Our simulations showed that this
      model explains the observed relationships between BasG and GCR during a three
      fold simulated increase in BasG. Our findings support the hypothesis that basal
      hyperglucagonemia contributes to the GCR impairment in T1DM and show that the
      predictive power of our GCR animal model applies to human pathophysiology in
      T1DM.

PMID- 22403551
TI  - Modulation of ion transport across rat distal colon by cysteine.
AB  - The aim of this study was to identify the actions of stimulation of endogenous
      production of H(2)S by cysteine, the substrate for the two H(2)S-producing
      enzymes, cystathionine-beta-synthase and cystathionine-gamma-lyase, on ion
      transport across rat distal colon. Changes in short-circuit current (Isc) induced
      by cysteine were measured in Ussing chambers. Free cysteine caused a
      concentration-dependent, transient fall in Isc, which was sensitive to amino
      oxyacetate and beta-cyano-L-alanine, i.e., inhibitors of H(2)S-producing enzymes.
      In contrast, Na cysteinate evoked a biphasic change in Isc, i.e., an initial fall
      followed by a secondary increase, which was also reduced by these enzyme
      inhibitors. All responses were dependent on the presence of Cl(-) and inhibited
      by bumetanide, suggesting that free cysteine induces an inhibition of
      transcellular Cl(-) secretion, whereas Na cysteinate - after a transient
      inhibitory phase - activates anion secretion. The assumed reason for this
      discrepancy is a fall in the cytosolic pH induced by free cysteine, but not by Na
      cysteinate, as observed in isolated colonic crypts loaded with the pH-sensitive
      dye, BCECF. Intracellular acidification is known to inhibit epithelial K(+)
      channels. Indeed, after preinhibition of basolateral K(+) channels with
      tetrapentylammonium or Ba(2+), the negative Isc induced by free cysteine was
      reduced significantly. In consequence, stimulation of endogenous H(2)S production
      by Na cysteinate causes, after a short inhibitory response, a delayed activation
      of anion secretion, which is missing in the case of free cysteine, probably due
      to the cytosolic acidification. In contrast, diallyl trisulfide, which is
      intracellularly converted to H(2)S, only evoked a monophasic increase in Isc
      without the initial fall observed with Na cysteinate. Consequently, time course
      and amount of produced H(2)S seem to strongly influence the functional response
      of the colonic epithelium evoked by this gasotransmitter.

PMID- 22403552
TI  - Affect Expression and Self-Regulation Capacities of Infants Exposed in utero to
      Psychotropics.
AB  - This study explored the affect expression and self-regulation capacities of 8
      month-old infants exposed in utero to psychotropic medications. This was a
      continuation of our previous study conducted on the same cohort when the infants
      were 3 months old. Psychotropics implicated included selective serotonin reuptake
      inhibitors (SSRIs), and a benzodiazepine derivative anxiolytic (clonazepam). The
      three comparison groups were: control (n = 23; infants not exposed to
      psychotropics in utero), SSRI-alone (n = 22; infants exposed to SSRIs only and
      having mothers who had a primary diagnosis of depressive disorder without having
      comorbid anxiety disorder), and SSRI+ group (n = 15; infants gestationally
      exposed to SSRIs and clonazepam and having mothers that had both clinical
      depression and anxiety disorder). Using the Parent-Child Early Relational
      Assessment Scale, infants were assessed in a dyadic context during free play and
      a structured task. There were significant differences in psychotropic exposed and
      non-exposed dyads regarding infant negative affect management. There were
      significant associations between the SSRI+ group of mothers and infant negative
      affect. This group of mothers also showed significant associations with infants'
      averting and avoiding behaviors in both play situations. The SSRI-alone group was
      similar to the control group and showed variable associations with infant's
      positive, negative, and sober moods unlike the SSRI+ group. There were no
      differences in infants' capacity for self-regulation in psychotropic exposed and
      non-exposed groups. Increased awareness of these vulnerable subgroups (SSRI-alone
      and SSRI+) is needed, in order to safeguard these dyads through better support
      systems and improved management.

PMID- 22403553
TI  - Task-related deactivation and functional connectivity of the subgenual cingulate
      cortex in major depressive disorder.
AB  - BACKGROUND: Major depressive disorder is associated with functional alterations
      in activity and resting-state connectivity of the extended medial frontal
      network. In this study we aimed to examine how task-related medial network
      activity and connectivity were affected in depression. METHODS: 18 patients with
      major depressive disorder, aged 15- to 24-years-old, were matched with 19 healthy
      control participants. We characterized task-related activations and deactivations
      while participants engaged with an executive-control task (the multi-source
      interference task, MSIT). We used a psycho-physiological interactions approach to
      examine functional connectivity changes with subgenual anterior cingulate cortex.
      Voxel-wise statistical maps for each analysis were compared between the patient
      and control groups. RESULTS: There were no differences between groups in their
      behavioral performances on the MSIT task, and nor in patterns of activation and
      deactivation. Assessment of functional connectivity with the subgenual cingulate
      showed that depressed patients did not demonstrate the same reduction in
      functional connectivity with the ventral striatum during task performance, but
      that they showed greater reduction in functional connectivity with adjacent
      ventromedial frontal cortex. The magnitude of this latter connectivity change
      predicted the relative activation of task-relevant executive-control regions in
      depressed patients. CONCLUSION: The study reinforces the importance of the
      subgenual cingulate cortex for depression, and demonstrates how dysfunctional
      connectivity with ventral brain regions might influence executive-attentional
      processes.

PMID- 22403554
TI  - Metal chaperones: a holistic approach to the treatment of Alzheimer's disease.
AB  - As evidence for the role of metal ion dysregulation in the pathogenesis of
      multiple CNS disorders grows, it has become important to more precisely identify
      and differentiate the biological effects of various pharmacological modulators of
      metal ion homeostasis. This is particularly evident in disorders such as
      Alzheimer's disease (AD), where the use of metal chaperones (that transport
      metals), as opposed to chelators (which exclude metals from biological
      interactions), may prove to be the first truly disease modifying approach for
      this condition. The purpose of this mini-review is to highlight the emerging
      notion that metal chaperones, such as PBT2 (Prana Biotechnology), modulate a
      variety of critical pathways affecting key aspects of the AD cascade to provide a
      more "holistic" approach to the treatment of this disease.

PMID- 22403556
TI  - Proactive interference does not meaningfully distort visual working memory
      capacity estimates in the canonical change detection task.
AB  - The change detection task has become a standard method for estimating the storage
      capacity of visual working memory. Most researchers assume that this task
      isolates the properties of an active short-term storage system that can be
      dissociated from long-term memory systems. However, long-term memory storage may
      influence performance on this task. In particular, memory traces from previous
      trials may create proactive interference that sometimes leads to errors, thereby
      reducing estimated capacity. Consequently, the capacity of visual working memory
      may be higher than is usually thought, and correlations between capacity and
      other measures of cognition may reflect individual differences in proactive
      interference rather than individual differences in the capacity of the short-term
      storage system. Indeed, previous research has shown that change detection
      performance can be influenced by proactive interference under some conditions.
      The purpose of the present study was to determine whether the canonical version
      of the change detection task - in which the to-be-remembered information consists
      of simple, briefly presented features - is influenced by proactive interference.
      Two experiments were conducted using methods that ordinarily produce substantial
      evidence of proactive interference, but no proactive interference was observed.
      Thus, the canonical version of the change detection task can be used to assess
      visual working memory capacity with no meaningful influence of proactive
      interference.

PMID- 22403557
TI  - Affective monitoring: a generic mechanism for affect elicitation.
AB  - In this paper we sketch a new framework for affect elicitation, which is based on
      previous evolutionary and connectionist modeling and experimental work from our
      group. Affective monitoring is considered a local match-mismatch process within a
      module of the neural network. Negative affect is raised instantly by mismatches,
      incongruency, disfluency, novelty, incoherence, and dissonance, whereas positive
      affect follows from matches, congruency, fluency, familiarity, coherence, and
      resonance, at least when an initial mismatch can be solved quickly. Affective
      monitoring is considered an evolutionary-early conflict and change detection
      process operating at the same level as, for instance, attentional selection. It
      runs in parallel and imparts affective flavor to emotional behavior systems,
      which involve evolutionary-prepared stimuli and action tendencies related to for
      instance defensive, exploratory, attachment, or appetitive behavior. Positive
      affect is represented in the networks by high-frequency oscillations, presumably
      in the gamma band. Negative affect corresponds to more incoherent lower-frequency
      oscillations, presumably in the theta band. For affect to become conscious, large
      scale synchronization of the oscillations over the network and the construction
      of emotional experiences are required. These constructions involve perceptions of
      bodily states and action tendencies, but also appraisals as well as efforts to
      regulate the emotion. Importantly, affective monitoring accompanies every kind of
      information processing, but conscious emotions, which result from the later
      integration of affect in a cognitive context, are much rarer events.

PMID- 22403558
TI  - How singing works.

PMID- 22403559
TI  - Music and language processing share behavioral and cerebral features.

PMID- 22403555
TI  - A-Subclass ATP-Binding Cassette Proteins in Brain Lipid Homeostasis and
      Neurodegeneration.
AB  - The A-subclass of ATP-binding cassette (ABC) transporters comprises 12
      structurally related members of the evolutionarily highly conserved superfamily
      of ABC transporters. ABCA transporters represent a subgroup of "full-size"
      multispan transporters of which several members have been shown to mediate the
      transport of a variety of physiologic lipid compounds across membrane barriers.
      The importance of ABCA transporters in human disease is documented by the
      observations that so far four members of this protein family (ABCA1, ABCA3,
      ABCA4, ABCA12) have been causatively linked to monogenetic disorders including
      familial high-density lipoprotein deficiency, neonatal surfactant deficiency,
      degenerative retinopathies, and congenital keratinization disorders. Recent
      research also point to a significant contribution of several A-subfamily ABC
      transporters to neurodegenerative diseases, in particular Alzheimer's disease
      (AD). This review will give a summary of our current knowledge of the A-subclass
      of ABC transporters with a special focus on brain lipid homeostasis and their
      involvement in AD.

PMID- 22403560
TI  - Episodic and Semantic Autobiographical Memory and Everyday Memory during Late
      Childhood and Early Adolescence.
AB  - Few studies have examined both episodic and semantic autobiographical memory (AM)
      performance during late childhood and early adolescence. Using the newly
      developed Children's Autobiographical Interview (CAI), the present study examined
      the effects of age and sex on episodic and semantic AM and everyday memory in 182
      children and adolescents. Results indicated that episodic and semantic AM both
      improved between 8 and 16 years of age; however, age-related changes were larger
      for episodic AM than for semantic AM. In addition, females were found to recall
      more episodic AM details, but not more semantic AM details, than males.
      Importantly, this sex difference in episodic AM recall was attenuated under
      conditions of high retrieval support (i.e., the use of probing questions). The
      ability to clearly visualize past events at the time of recollection was related
      to children's episodic AM recall performance, particularly the retrieval of
      perceptual details. Finally, similar age and sex effects were found between
      episodic AM and everyday memory ability (e.g., memory for everyday activities).
      More specifically, older participants and females exhibited better episodic AM
      and everyday memory performance than younger participants and males. Overall, the
      present study provides important new insight into both episodic and semantic AM
      performance, as well as the relation between episodic AM and everyday memory,
      during late childhood and adolescence.

PMID- 22403561
TI  - Old and new ideas for data screening and assumption testing for exploratory and
      confirmatory factor analysis.
AB  - We provide a basic review of the data screening and assumption testing issues
      relevant to exploratory and confirmatory factor analysis along with practical
      advice for conducting analyses that are sensitive to these concerns.
      Historically, factor analysis was developed for explaining the relationships
      among many continuous test scores, which led to the expression of the common
      factor model as a multivariate linear regression model with observed, continuous
      variables serving as dependent variables, and unobserved factors as the
      independent, explanatory variables. Thus, we begin our paper with a review of the
      assumptions for the common factor model and data screening issues as they pertain
      to the factor analysis of continuous observed variables. In particular, we
      describe how principles from regression diagnostics also apply to factor
      analysis. Next, because modern applications of factor analysis frequently involve
      the analysis of the individual items from a single test or questionnaire, an
      important focus of this paper is the factor analysis of items. Although the
      traditional linear factor model is well-suited to the analysis of continuously
      distributed variables, commonly used item types, including Likert-type items,
      almost always produce dichotomous or ordered categorical variables. We describe
      how relationships among such items are often not well described by product-moment
      correlations, which has clear ramifications for the traditional linear factor
      analysis. An alternative, non-linear factor analysis using polychoric
      correlations has become more readily available to applied researchers and thus
      more popular. Consequently, we also review the assumptions and data-screening
      issues involved in this method. Throughout the paper, we demonstrate these
      procedures using an historic data set of nine cognitive ability variables.

PMID- 22403562
TI  - Time Dilation Induced by Object Motion is Based on Spatiotopic but not
      Retinotopic Positions.
AB  - Time perception of visual events depends on the visual attributes of the scene.
      Previous studies reported that motion of object can induce an illusion of
      lengthened time. In the present study, we asked the question whether such time
      dilation effect depends on the actual physical motion of the object (spatiotopic
      coordinate), or its relative motion with respect to the retina (retinotopic
      coordinate). Observers were presented with a moving stimulus and a static
      reference stimulus in separate intervals, and judged which interval they
      perceived as having a longer duration, under conditions with eye fixation
      (Experiment 1) and with eye movement at same velocity as the moving stimulus
      (Experiment 2). The data indicated that the perceived duration was longer under
      object motion, and depended on the actual movement of the object rather than
      relative retinal motion. These results are in support with the notion that the
      brain possesses a spatiotopic representation regarding the real world positions
      of objects in which the perception of time is associated with.

PMID- 22403563
TI  - Proactive inhibitory control of response as the default state of executive
      control.
AB  - Refraining from reacting does not only involve reactive inhibitory mechanisms. It
      was recently found that inhibitory control also relies strongly on proactive
      mechanisms. However, since most available studies have focused on reactive
      stopping, little is known about how proactive inhibition of response is
      implemented. Two behavioral experiments were conducted to identify the temporal
      dynamics of this executive function. They manipulated respectively the time
      during which inhibitory control must be sustained until a stimulus occurs, and
      the time limit allowed to set up inhibition before a stimulus occurs. The results
      show that inhibitory control is not set up after but before instruction, and is
      not transient and sporadic but sustained across time. Consistent with our
      previous neuroimaging findings, these results suggest that proactive inhibition
      of response is the default mode of executive control. This implies that top-down
      control of sensorimotor reactivity would consist of a temporary release (up to
      several seconds), when appropriate (when the environment becomes predictable), of
      the default locking state. This conclusion is discussed with regard to current
      anatomo-functional models of inhibitory control, and to methodological features
      of studies of attention and sensorimotor control.

PMID- 22403564
TI  - Mapping symbols to sounds: electrophysiological correlates of the impaired
      reading process in dyslexia.
AB  - Dyslexic and control first-grade school children were compared in a Symbol-to
      Sound matching test based on a non-linguistic audiovisual training which is known
      to have a remediating effect on dyslexia. Visual symbol patterns had to be
      matched with predicted sound patterns. Sounds incongruent with the corresponding
      visual symbol (thus not matching the prediction) elicited the N2b and P3a event
      related potential (ERP) components relative to congruent sounds in control
      children. Their ERPs resembled the ERP effects previously reported for healthy
      adults with this paradigm. In dyslexic children, N2b onset latency was delayed
      and its amplitude significantly reduced over left hemisphere whereas P3a was
      absent. Moreover, N2b amplitudes significantly correlated with the reading
      skills. ERPs to sound changes in a control condition were unaffected. In
      addition, correctly predicted sounds, that is, sounds that are congruent with the
      visual symbol, elicited an early induced auditory gamma band response (GBR)
      reflecting synchronization of brain activity in normal-reading children as
      previously observed in healthy adults. However, dyslexic children showed no GBR.
      This indicates that visual symbolic and auditory sensory information are not
      integrated into a unitary audiovisual object representation in them. Finally,
      incongruent sounds were followed by a later desynchronization of brain activity
      in the gamma band in both groups. This desynchronization was significantly larger
      in dyslexic children. Although both groups accomplished the task successfully
      remarkable group differences in brain responses suggest that normal-reading
      children and dyslexic children recruit (partly) different brain mechanisms when
      solving the task. We propose that abnormal ERPs and GBRs in dyslexic readers
      indicate a deficit resulting in a widespread impairment in processing and
      integrating auditory and visual information and contributing to the reading
      impairment in dyslexia.

PMID- 22403565
TI  - Arousal modulates auditory attention and awareness: insights from sleep,
      sedation, and disorders of consciousness.
AB  - The interplay between attention and consciousness is frequently tested in altered
      states of consciousness, including transitions between stages of sleep and
      sedation, and in pathological disorders of consciousness (DoC; the vegetative and
      minimally conscious states; VS and MCS). One of the most widely used tasks to
      assess cognitive processing in this context is the auditory oddball paradigm,
      where an infrequent change in a sequence of sounds elicits, in awake subjects, a
      characteristic EEG event-related potential called the mismatch negativity,
      followed by the classic P300 wave. The latter is further separable into the
      slightly earlier, anterior P3a and the later, posterior P3b, thought to be linked
      to task-irrelevant "bottom-up" and task-oriented "top-down" attention,
      respectively. We discuss here the putative dissociations between attention and
      awareness in DoC, sedation and sleep, bearing in mind the recently emerging
      evidence from healthy volunteers and patients. These findings highlight the
      neurophysiological and cognitive parallels (and differences) across these three
      distinct variations in levels of consciousness, and inform the theoretical
      framework for interpreting the role of attention therein.

PMID- 22403566
TI  - Fos expression in neurons of the rat vestibulo-autonomic pathway activated by
      sinusoidal galvanic vestibular stimulation.
AB  - The vestibular system sends projections to brainstem autonomic nuclei that
      modulate heart rate and blood pressure in response to changes in head and body
      position with regard to gravity. Consistent with this, binaural sinusoidally
      modulated galvanic vestibular stimulation (sGVS) in humans causes
      vasoconstriction in the legs, while low frequency (0.02-0.04 Hz) sGVS causes a
      rapid drop in heart rate and blood pressure in anesthetized rats. We have
      hypothesized that these responses occur through activation of vestibulo
      sympathetic pathways. In the present study, c-Fos protein expression was examined
      in neurons of the vestibular nuclei and rostral ventrolateral medullary region
      (RVLM) that were activated by low frequency sGVS. We found c-Fos-labeled neurons
      in the spinal, medial, and superior vestibular nuclei (SpVN, MVN, and SVN,
      respectively) and the parasolitary nucleus. The highest density of c-Fos-positive
      vestibular nuclear neurons was observed in MVN, where immunolabeled cells were
      present throughout the rostro-caudal extent of the nucleus. c-Fos expression was
      concentrated in the parvocellular region and largely absent from magnocellular
      MVN. c-Fos-labeled cells were scattered throughout caudal SpVN, and the
      immunostained neurons in SVN were restricted to a discrete wedge-shaped area
      immediately lateral to the IVth ventricle. Immunofluorescence localization of c
      Fos and glutamate revealed that approximately one third of the c-Fos-labeled
      vestibular neurons showed intense glutamate-like immunofluorescence, far in
      excess of the stain reflecting the metabolic pool of cytoplasmic glutamate. In
      the RVLM, which receives a direct projection from the vestibular nuclei and sends
      efferents to preganglionic sympathetic neurons in the spinal cord, we observed an
      approximately threefold increase in c-Fos labeling in the sGVS-activated rats. We
      conclude that localization of c-Fos protein following sGVS is a reliable marker
      for sGVS-activated neurons of the vestibulo-sympathetic pathway.

PMID- 22403567
TI  - Neuro-glial and systemic mechanisms of pathological responses in rat models of
      primary blast overpressure compared to "composite" blast.
AB  - A number of experimental models of blast brain injury have been implemented in
      rodents and larger animals. However, the variety of blast sources and the
      complexity of blast wave biophysics have made data on injury mechanisms and
      biomarkers difficult to analyze and compare. Recently, we showed the importance
      of rat position toward blast generated by an external shock tube. In this study,
      we further characterized blast producing moderate traumatic brain injury and
      defined "composite" blast and primary blast exposure set-ups. Schlieren optics
      visualized interaction between the head and a shock wave generated by external
      shock tube, revealing strong head acceleration upon positioning the rat on-axis
      with the shock tube (composite blast), but negligible skull movement upon peak
      overpressure exposure off-axis (primary blast). Brain injury signatures of a
      primary blast hitting the frontal head were assessed and compared to damage
      produced by composite blast. Low to negligible levels of neurodegeneration were
      found following primary blast compared to composite blast by silver staining.
      However, persistent gliosis in hippocampus and accumulation of GFAP/CNPase in
      circulation was detected after both primary and composite blast. Also, markers of
      vascular/endothelial inflammation integrin alpha/beta, soluble intercellular
      adhesion molecule-1, and L-selectin along with neurotrophic factor nerve growth
      factor-beta were increased in serum within 6 h post-blasts and persisted for 7
      days thereafter. In contrast, systemic IL-1, IL-10, fractalkine, neuroendocrine
      peptide Orexin A, and VEGF receptor Neuropilin-2 (NRP-2) were raised
      predominantly after primary blast exposure. In conclusion, biomarkers of major
      pathological pathways were elevated at all blast set-ups. The most significant
      and persistent changes in neuro-glial markers were found after composite blast,
      while primary blast instigated prominent systemic cytokine/chemokine, Orexin A,
      and Neuropilin-2 release, particularly when primary blast impacted rats with
      unprotected body.

PMID- 22403568
TI  - The effects of bilateral vestibular loss on hippocampal volume, neuronal number,
      and cell proliferation in rats.
AB  - Previous studies in humans have shown that bilateral loss of vestibular function
      is associated with a significant bilateral atrophy of the hippocampus, which
      correlated with the patients' spatial memory deficits. More recently, patients
      who had recovered from unilateral vestibular neuritis have been reported to
      exhibit a significant atrophy of the left posterior hippocampus. Therefore, we
      investigated whether bilateral vestibular deafferentation (BVD) would result in a
      decrease in neuronal number or volume in the rat hippocampus, using stereological
      methods. At 16 months post-BVD, we found no significant differences in
      hippocampal neuronal number or volume compared to sham controls, despite the fact
      that these animals exhibited severe spatial memory deficits. By contrast, using
      bromodeoxyuridine (BrdU) as a marker of cell proliferation, we found that the
      number of BrdU-labeled cells significantly increased in the dentate gyrus of the
      hippocampus between 48 h and 1 week following BVD. Although a substantial
      proportion of these cells survived for up to 1 month, the survival rate was
      significantly lower in BVD animals when compared with that in sham animals. These
      results suggest a dissociation between the effects of BVD on spatial memory and
      hippocampal structure in rats and humans, which cannot be explained by an injury
      induced increase in cell proliferation.

PMID- 22403569
TI  - Plasticity during Vestibular Compensation: The Role of Saccades.
AB  - THIS PAPER IS FOCUSED ON ONE MAJOR ASPECT OF COMPENSATION: the recent measures of
      saccadic responses to high acceleration head turns during human vestibular
      compensation and their possible implications for recovery after unilateral
      vestibular loss (UVL). New measurement techniques have provided additional
      insights into how patients recover after UVL and have given clues for vestibular
      rehabilitation. Prior to this it has not been possible to quantify the level of
      function of all the peripheral vestibular sense organs. Now it is. By using
      vestibular-evoked myogenic potentials to measure utricular and saccular function
      and by new video head impulse testing to measure semicircular canal function to
      natural values of head accelerations. With these new video procedures it is now
      possible to measure both slow phase eye velocity and also saccades during head
      movements with natural values of angular acceleration. The present evidence is
      that after UVL there is little or no restoration/compensation of slow phase eye
      velocity responses to natural head accelerations. It is doubtful as to whether
      the modest changes in slow phase eye velocity to small angular accelerations are
      functionally effective during compensation. On the other hand it is now clear
      that saccades can play a very important role in helping patients compensate and
      return to a normal lifestyle. Preliminary evidence suggests that different
      patterns of saccadic response may predict how well patients recover. Furthermore
      it may be possible to train patients to produce more effective saccadic patterns
      in the first days after their unilateral loss and possibly improve their
      compensation process. Some patients do learn new strategies, new behaviors, to
      conceal their inadequate vestibulo-ocular response but when those strategies are
      prevented from operating by using passive, unpredictable, high acceleration
      natural head movements, as in the head impulse test, the vestibular loss can be
      demonstrated. It is those very strategies which the tests exclude, which may be
      the cause of their successful compensation.

PMID- 22403571
TI  - Where will the (New) Drugs for Traumatic Brain Injury Treatment be Coming From?

PMID- 22403570
TI  - Reconsidering the role of neuronal intrinsic properties and neuromodulation in
      vestibular homeostasis.
AB  - The sensorimotor transformations performed by central vestibular neurons
      constantly adapt as the animal faces conflicting sensory information or sustains
      injuries. To ensure the homeostasis of vestibular-related functions, neural
      changes could in part rely on the regulation of 2 degrees  VN intrinsic
      properties. Here we review evidence that demonstrates modulation and plasticity
      of central vestibular neurons' intrinsic properties. We first present the
      partition of Rodents' vestibular neurons into distinct subtypes, namely type A
      and type B. Then, we focus on the respective properties of each type, their
      putative roles in vestibular functions, fast control by neuromodulators and
      persistent modifications following a lesion. The intrinsic properties of central
      vestibular neurons can be swiftly modulated by a wealth of neuromodulators to
      adapt rapidly to temporary changes of ecophysiological surroundings. To
      illustrate how intrinsic excitability can be rapidly modified in physiological
      conditions and therefore be therapeutic targets, we present the modulation of
      vestibular reflexes in relation to the variations of the neuromodulatory inputs
      during the sleep/wake cycle. On the other hand, intrinsic properties can also be
      slowly, yet permanently, modified in response to major perturbations, e.g., after
      unilateral labyrinthectomy (UL). We revisit the experimental evidence, which
      demonstrates that drastic alterations of the central vestibular neurons'
      intrinsic properties occur following UL, with a slow time course, more on par
      with the compensation of dynamic deficits than static ones. Data are interpreted
      in the framework of distributed processes that progress from global, large-scale
      coping mechanisms (e.g., changes in behavioral strategies) to local, small-scale
      ones (e.g., changes in intrinsic properties). Within this framework, the
      compensation of dynamic deficits improves over time as deeper modifications are
      engraved within the finer parts of the vestibular-related networks. Finally, we
      offer perspectives and working hypotheses to pave the way for future research
      aimed at understanding the modulation and plasticity of central vestibular
      neurons' intrinsic properties.

PMID- 22403572
TI  - Assessment of the effects of acute and repeated exposure to blast overpressure in
      rodents: toward a greater understanding of blast and the potential ramifications
      for injury in humans exposed to blast.
AB  - Mild traumatic brain injury (mTBI) resulting from exposure to improvised
      explosive devices (IEDs) has fueled a requirement to develop animals models that
      mirror this condition using exposure to blast overpressure (BOP). En route to
      developing a model of repeated exposure to BOP we sought to initially
      characterize the effects of acute BOP exposure in rodents, focusing specifically
      on the levels of BOP exposure that produced clinical mTBI symptoms. We first
      measured BOP effects on gross motor function on a balance beam. Separate groups
      of unanesthetized rats were exposed (in different orientations) to 36.6, 74.5,
      and 116.7 kPa BOP exposure inside a pneumatically driven shock tube. Results
      demonstrated that rats exposed to 116.7 kPa demonstrated transient alterations or
      loss of consciousness indicated by a transient loss of righting and by increased
      latencies on the balance beam. The 116.7 kPa exposure was the threshold for overt
      pathology for acute BOP exposure with approximately 30% of rats presenting with
      evidence of subdural hemorrhage and cortical contusions. All animals exposed to
      116.7 kPa BOP manifested evidence of significant pulmonary hemorrhage.
      Anterograde memory deficits were observed in rats exposed to 74.5 kPa facing the
      BOP wave and rats exposed to 116.7 kPa in the lateral (side) orientation. We next
      assessed repeated exposure to either lateral or frontal 36.6 kPa BOP in
      anesthetized rats, once per day for 12 days. Results showed that repeated
      exposure in the frontal, but not side, orientation to the BOP wave produced a
      transitory learning deficit on a Morris water maze task as shown by significantly
      longer latencies to reach the submerged platform in the second and third blocks
      of a four block session. Implications of these data are discussed in relation to
      the manifestation of mTBI in military personnel exposed to IEDs. Finally, we
      suggest that there are multiple types of long-term brain injury from blast
      exposure.

PMID- 22403574
TI  - The organic complexation of iron in the marine environment: a review.
AB  - Iron (Fe) is an essential micronutrient for marine organisms, and it is now well
      established that low Fe availability controls phytoplankton productivity,
      community structure, and ecosystem functioning in vast regions of the global
      ocean. The biogeochemical cycle of Fe involves complex interactions between
      lithogenic inputs (atmospheric, continental, or hydrothermal), dissolution,
      precipitation, scavenging, biological uptake, remineralization, and sedimentation
      processes. Each of these aspects of Fe biogeochemical cycling is likely
      influenced by organic Fe-binding ligands, which complex more than 99% of
      dissolved Fe. In this review we consider recent advances in our knowledge of Fe
      complexation in the marine environment and their implications for the
      biogeochemistry of Fe in the ocean. We also highlight the importance of
      constraining the dissolved Fe concentration value used in interpreting
      voltammetric titration data for the determination of Fe speciation. Within the
      published Fe speciation data, there appear to be important temporal and spatial
      variations in Fe-binding ligand concentrations and their conditional stability
      constants in the marine environment. Excess ligand concentrations, particularly
      in the truly soluble size fraction, seem to be consistently higher in the upper
      water column, and especially in Fe-limited, but productive, waters. Evidence is
      accumulating for an association of Fe with both small, well-defined ligands, such
      as siderophores, as well as with larger, macromolecular complexes like humic
      substances, exopolymeric substances, and transparent exopolymers. The diverse
      size spectrum and chemical nature of Fe ligand complexes corresponds to a change
      in kinetic inertness which will have a consequent impact on biological
      availability. However, much work is still to be done in coupling voltammetry,
      mass spectrometry techniques, and process studies to better characterize the
      nature and cycling of Fe-binding ligands in the marine environment.

PMID- 22403573
TI  - Modulation of Immune System by Kaposi's Sarcoma-Associated Herpesvirus: Lessons
      from Viral Evasion Strategies.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), a member of the herpesvirus
      family, has evolved to establish a long-term, latent infection of cells such that
      while they carry the viral genome gene expression is highly restricted. Latency
      is a state of cryptic viral infection associated with genomic persistence in
      their host and this hallmark of KSHV infection leads to several clinical
      epidemiological diseases such as KS, a plasmablastic variant of multicentric
      Castleman's disease, and primary effusion lymphoma upon immune suppression of
      infected hosts. In order to sustain efficient life-long persistency as well as
      their life cycle, KSHV dedicates a large portion of its genome to encode
      immunomodulatory proteins that antagonize its host's immune system. In this
      review, we will describe our current knowledge of the immune evasion strategies
      employed by KSHV at distinct stages of its viral life cycle to control the host's
      immune system.

PMID- 22403575
TI  - Sulfate-reducing microorganisms in wetlands - fameless actors in carbon cycling
      and climate change.
AB  - Freshwater wetlands are a major source of the greenhouse gas methane but at the
      same time can function as carbon sink. Their response to global warming and
      environmental pollution is one of the largest unknowns in the upcoming decades to
      centuries. In this review, we highlight the role of sulfate-reducing
      microorganisms (SRM) in the intertwined element cycles of wetlands. Although
      regarded primarily as methanogenic environments, biogeochemical studies have
      revealed a previously hidden sulfur cycle in wetlands that can sustain rapid
      renewal of the small standing pools of sulfate. Thus, dissimilatory sulfate
      reduction, which frequently occurs at rates comparable to marine surface
      sediments, can contribute up to 36-50% to anaerobic carbon mineralization in
      these ecosystems. Since sulfate reduction is thermodynamically favored relative
      to fermentative processes and methanogenesis, it effectively decreases gross
      methane production thereby mitigating the flux of methane to the atmosphere.
      However, very little is known about wetland SRM. Molecular analyses using dsrAB
      [encoding subunit A and B of the dissimilatory (bi)sulfite reductase] as marker
      genes demonstrated that members of novel phylogenetic lineages, which are
      unrelated to recognized SRM, dominate dsrAB richness and, if tested, are also
      abundant among the dsrAB-containing wetland microbiota. These discoveries point
      toward the existence of so far unknown SRM that are an important part of the
      autochthonous wetland microbiota. In addition to these numerically dominant
      microorganisms, a recent stable isotope probing study of SRM in a German peatland
      indicated that rare biosphere members might be highly active in situ and have a
      considerable stake in wetland sulfate reduction. The hidden sulfur cycle in
      wetlands and the fact that wetland SRM are not well represented by described SRM
      species explains their so far neglected role as important actors in carbon
      cycling and climate change.

PMID- 22403576
TI  - Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation:
      Multicentric Castleman Disease (KSHV-MCD) and the KSHV Inflammatory Cytokine
      Syndrome.
AB  - Soon after the discovery of Kaposi sarcoma (KS)-associated herpesvirus (KSHV), it
      was appreciated that this virus was associated with most cases of multicentric
      Castleman disease (MCD) arising in patients infected with human immunodeficiency
      virus. It has subsequently been recognized that KSHV-MCD is a distinct entity
      from other forms of MCD. Like MCD that is unrelated to KSHV, the clinical
      presentation of KSHV-MCD is dominated by systemic inflammatory symptoms including
      fevers, cachexia, and laboratory abnormalities including cytopenias,
      hypoalbuminemia, hyponatremia, and elevated C-reactive protein. Pathologically
      KSHV-MCD is characterized by polyclonal, IgM-lambda restricted plasmacytoid cells
      in the intrafollicular areas of affected lymph nodes. A portion of these cells
      are infected with KSHV and a sizable subset of these cells express KSHV lytic
      genes including a viral homolog of interleukin-6 (vIL-6). Patients with KSHV-MCD
      generally have elevated KSHV viral loads in their peripheral blood. Production of
      vIL-6 and induction of human (h) IL-6 both contribute to symptoms, perhaps in
      combination with overproduction of IL-10 and other cytokines. Until recently, the
      prognosis of patients with KSHV-MCD was poor. Recent therapeutic advances
      targeting KSHV-infected B cells with the anti-CD20 monoclonal antibody rituximab
      and utilizing KSHV enzymes to target KSHV-infected cells have substantially
      improved patient outcomes. Recently another KSHV-associated condition, the KSHV
      inflammatory cytokine syndrome (KICS) has been described. Its clinical
      manifestations resemble those of KSHV-MCD but lymphadenopathy is not prominent
      and the pathologic nodal changes of KSHV-MCD are absent. Patients with KICS
      exhibit elevated KSHV viral loads and elevation of vIL-6, homolog of human
      interleukin-6 and IL-10 comparable to those seen in KSHV-MCD; the cellular origin
      of these is a matter of investigation. KICS may contribute to the inflammatory
      symptoms seen in some patients with severe KS or primary effusion lymphoma.
      Additional research is needed to better define the clinical spectrum of KICS and
      its relationship to KSHV-MCD. In additional, research is needed to better
      understand the pathogenesis and epidemiology of both KICS and KSHV-MCD, as well
      as the optimal therapy for both of these disorders.

PMID- 22403577
TI  - Morbillivirus receptors and tropism: multiple pathways for infection.
AB  - Morbilliviruses, which include measles virus (MeV), canine distemper virus, and
      rinderpest virus, are among the most important pathogens in their respective
      hosts and cause severe syndromes. Morbilliviruses are enveloped viruses with two
      envelope proteins, one of which is hemagglutinin (H) protein, which plays a role
      in binding to cellular receptors. During morbillivirus infection, the virus
      initially targets lymphoid cells and replicates efficiently in the lymph nodes.
      The principal cellular receptor for morbillivirus is signaling lymphocyte
      activation molecule (SLAM, also called CD150), which is exclusively expressed on
      immune cells. This feature reflects the strong lymphoid cell tropism and viral
      spread in the infected body. Morbillivirus infection, however, affects various
      tissues in the body, including the lung, kidney, gastrointestinal tract, vascular
      endothelium, and brain. Thus, other receptors for morbilliviruses in addition to
      SLAM might exist. Recently, nectin-4 has been identified as a novel epithelial
      cell receptor for MeV. The expression of nectin-4 is localized to polarized
      epithelial cells, and this localization supports the notion of cell tropism since
      MeV also grows well in the epithelial cells of the respiratory tract. Although
      two major receptors for lymphoid and epithelial cells in natural infection have
      been identified, morbillivirus can still infect many other types of cells with
      low infectivity, suggesting the existence of inefficient but ubiquitously
      expressed receptors. We have identified other molecules that are implicated in
      morbillivirus infection of SLAM-negative cells by alternative mechanisms. These
      findings indicate that morbillivirus utilizes multiple pathways for establishment
      of infection. These studies will advance our understanding of morbillivirus
      tropism and pathogenesis.

PMID- 22403578
TI  - Fluctuations in Ammonia Oxidizing Communities Across Agricultural Soils are
      Driven by Soil Structure and pH.
AB  - The milieu in soil in which microorganisms dwell is never constant. Conditions
      such as temperature, water availability, pH and nutrients frequently change,
      impacting the overall functioning of the soil system. To understand the effects
      of such factors on soil functioning, proxies (indicators) of soil function are
      needed that, in a sensitive manner, reveal normal amplitude of variation. Thus,
      the so-called normal operating range (NOR) of soil can be defined. In this study
      we determined different components of nitrification by analyzing, in eight
      agricultural soils, how the community structures and sizes of ammonia oxidizing
      bacteria and archaea (AOB and AOA, respectively), and their activity, fluctuate
      over spatial and temporal scales. The results indicated that soil pH and soil
      type are the main factors that influence the size and structure of the AOA and
      AOB, as well as their function. The nitrification rates varied between 0.11 +/-
      0.03 MUgN h(-1) gdw(-1) and 1.68 +/- 0.11 MUgN h(-1) gdw(-1), being higher in
      soils with higher clay content (1.09 +/- 0.12 MUgN h(-1) gdw(-1)) and lower in
      soils with lower clay percentages (0.27 +/- 0.04 MUgN h(-1) gdw(-1)). Nitrifying
      activity was driven by soil pH, mostly related to its effect on AOA but not on
      AOB abundance. Regarding the influence of soil parameters, clay content was the
      main soil factor shaping the structure of both the AOA and AOB communities.
      Overall, the potential nitrifying activities were higher and more variable over
      time in the clayey than in the sandy soils. Whereas the structure of AOB
      fluctuated more (62.7 +/- 2.10%) the structure of AOA communities showed lower
      amplitude of variation (53.65 +/- 3.37%). Similar trends were observed for the
      sizes of these communities. The present work represents a first step toward
      defining a NOR for soil nitrification. The sensitivity of the process and
      organisms to impacts from the milieu support their use as proxies in the NOR of
      agricultural soils. Moreover, the clear effect of soil texture established here
      suggests that the NOR should be defined in a soil type-specific manner.

PMID- 22403579
TI  - Microbial CH(4) and N(2)O Consumption in Acidic Wetlands.
AB  - Acidic wetlands are global sources of the atmospheric greenhouse gases methane
      (CH(4)), and nitrous oxide (N(2)O). Consumption of both atmospheric gases has
      been observed in various acidic wetlands, but information on the microbial
      mechanisms underlying these phenomena is scarce. A substantial amount of CH(4) is
      consumed in sub soil by aerobic methanotrophs at anoxic-oxic interfaces (e.g.,
      tissues of Sphagnum mosses, rhizosphere of vascular plant roots). Methylocystis
      related species are likely candidates that are involved in the consumption of
      atmospheric CH(4) in acidic wetlands. Oxygen availability regulates the activity
      of methanotrophs of acidic wetlands. Other parameters impacting on the
      methanotroph-mediated CH(4) consumption have not been systematically evaluated.
      N(2)O is produced and consumed by microbial denitrification, thus rendering
      acidic wetlands as temporary sources or sinks for N(2)O. Denitrifier communities
      in such ecosystems are diverse, and largely uncultured and/or new, and
      environmental factors that control their consumption activity are unresolved.
      Analyses of the composition of N(2)O reductase genes in acidic wetlands suggest
      that acid-tolerant Proteobacteria have the potential to mediate N(2)O consumption
      in such soils. Thus, the fragmented current state of knowledge raises open
      questions concerning methanotrophs and denitrifiers that consume atmospheric
      CH(4) and N(2)O in acidic wetlands.

PMID- 22403580
TI  - Surface architecture of fungal pathogens.

PMID- 22403581
TI  - The Presence of the DNA Repair Genes mutM, mutY, mutL, and mutS is Related to
      Proteome Size in Bacterial Genomes.
AB  - DNA repair is expected to be a modulator of underlying mutation rates, however
      the major factors affecting the distribution of DNA repair pathways have not been
      determined. The Proteomic Constraint theory proposes that mutation rates are
      inversely proportional to the amount of heredity information contained in a
      genome, which is effectively the proteome. Thus, organisms with larger proteomes
      are expected to possess more efficient DNA repair. We show that an important
      factor influencing the presence or absence of four DNA repair genes mutM, mutY,
      mutL, and mutS is indeed the size of the bacterial proteome. This is true both of
      intracellular and other bacteria. In addition, the relationship of DNA repair to
      genome GC content was examined. In principle, if a DNA repair pathway is biased
      in the types of mutations it corrects, this may alter the genome GC content. The
      presence of the mismatch repair genes mutL and mutS was not correlated with
      genome GC content, consistent with their involvement in an unbiased DNA repair
      pathway. In contrast, the presence of the base excision repair genes mutM and
      mutY, whose products both correct GC -> AT mutations, was positively correlated
      with genome GC content, consistent with their biased repair mechanism.
      Phylogenetic analysis however indicates that the relationship between the
      presence of mutM and mutY genes and genome GC content is not a simple one.

PMID- 22403582
TI  - The limitations of locus specific methylation qualification and quantification in
      clinical material.
AB  - The terms methylation quantification and qualification seem self-explanatory
      however, the results of experiments aiming to quantify or qualify locus specific
      methylation in clinical material are often difficult to interpret. There are
      three main reasons for difficulties in understanding methylation status
      measurement. First, the complexity of locus specific methylation patterns, which
      oscillate between unmethylated, fully methylated, and heterogeneously methylated.
      Second the interpretation of methylation-screening results can frequently be
      problematic due to limitations of the methods used. And finally the
      specifications of the clinical samples used in laboratory practice frequently
      hamper the methylation measurement. Thus, the process of quantification and
      qualification of methylation has to be discussed with consideration of the
      specific locus analyzed, the methodology used, and the clinical material source
      used in each specific experiment. The question of the clinical significance of
      determination of different methylation levels is even more complicated, with
      substantial evidence for correlation between qualitative methylation changes and
      clinical features of the disease and at the same time no data showing that
      different relative levels of methylation alter the disease outcome. The
      limitations of methylation quantification and qualification are discussed in this
      mini-review.

PMID- 22403583
TI  - Accuracy of Genome-Enabled Prediction in a Dairy Cattle Population using
      Different Cross-Validation Layouts.
AB  - The impact of extent of genetic relatedness on accuracy of genome-enabled
      predictions was assessed using a dairy cattle population and alternative cross
      validation (CV) strategies were compared. The CV layouts consisted of training
      and testing sets obtained from either random allocation of individuals (RAN) or
      from a kernel-based clustering of individuals using the additive relationship
      matrix, to obtain two subsets that were as unrelated as possible (UNREL), as well
      as a layout based on stratification by generation (GEN). The UNREL layout
      decreased the average genetic relationships between training and testing animals
      but produced similar accuracies to the RAN design, which were about 15% higher
      than in the GEN setting. Results indicate that the CV structure can have an
      important effect on the accuracy of whole-genome predictions. However, the
      connection between average genetic relationships across training and testing sets
      and the estimated predictive ability is not straightforward, and may depend also
      on the kind of relatedness that exists between the two subsets and on the
      heritability of the trait. For high heritability traits, close relatives such as
      parents and full-sibs make the greatest contributions to accuracy, which can be
      compensated by half-sibs or grandsires in the case of lack of close relatives.
      However, for the low heritability traits the inclusion of close relatives is
      crucial and including more relatives of various types in the training set tends
      to lead to greater accuracy. In practice, CV designs should resemble the intended
      use of the predictive models, e.g., within or between family predictions, or
      within or across generation predictions, such that estimation of predictive
      ability is consistent with the actual application to be considered.

PMID- 22403584
TI  - Generation of a multi-locus chicken introgression line to study the effects of
      genetic interactions on metabolic phenotypes in chickens.
AB  - Most biological traits are regulated by a complex interplay between genetic and
      environmental factors. By intercrossing divergent lines, it is possible to
      identify individual and interacting QTL involved in the genetic architecture of
      these traits. When the loci have been mapped, alternative strategies are needed
      for fine-mapping and studying the individual and interactive effects of the QTL
      in detail. We have previously identified, replicated, and fine mapped a four
      locus QTL network that determines nearly half of the eightfold difference in body
      weight at 56 days of age between two divergently selected chicken lines. Here, we
      describe, to our knowledge, the first generation of a three-locus QTL
      introgression line in chickens. Recurrent marker-assisted backcrossing was used
      to simultaneously transfer QTL alleles from the low-weight selected line into the
      high-weight selected line. Three generations of backcrossing and one generation
      of intercrossing resulted in an introgression line where all three introgressed
      QTL and several unlinked and linked control-loci were segregating at nearly
      expected allele frequencies. We show how intensive selection can be applied using
      artificial insemination to rapidly generate a multi-locus introgression line and
      provide recommendations for future breeding of introgression lines. This
      confirmed introgression line will facilitate later detailed studies of the
      effects of genetic interactions on complex traits in this population, including
      growth, and body-composition traits.

PMID- 22403585
TI  - Bioinformatic Resources of microRNA Sequences, Gene Targets, and Genetic
      Variation.
AB  - Variation in quantitative gene expression has been observed in natural
      populations and associated with various complex traits/phenotypes such as risks
      for common diseases and drug response. MicroRNAs (miRNAs), a family of small, non
      coding RNA molecules, have been demonstrated to be an important class of gene
      regulators that mostly downregulate gene expression at the post-transcriptional
      level. A comprehensive and reliable catalogue of miRNAs and miRNA gene targets is
      critical to understanding the gene regulatory networks. Though experimental
      approaches have been used to identify many miRNAs and their gene targets, due to
      cost and efficiency, currently miRNA and target identification still largely
      relies on computational algorithms. We reviewed several widely used bioinformatic
      resources of miRNA sequences and gene targets that take advantage of the unique
      characteristics of miRNA-mRNA interactions, experimental validation, as well as
      the integration of sequence-based evidence and microarray expression data.
      Furthermore, given the importance of miRNAs in regulating gene expression,
      elucidating expression quantitative trait loci involved with miRSNPs or miR
      polymorphisms will help improve our understanding of complex traits. We reviewed
      the available resources of miRNA genetic variation, and the current progress
      (e.g., the 1000 Genomes Project) in detailing the genetic variation in miRNA
      related single nucleotide polymorphisms (SNPs). We also provided our perspectives
      of the potential impact of next-generation sequencing on the research of miRNAs,
      gene targets, and miRSNPs. These bioinformatic resources may help interpret
      experimental and association study results, thus enhancing our knowledge of the
      dynamic gene regulatory networks and the physiological pathways for complex
      traits/phenotypes. Prospectively, these bioinformatic resources of miRNAs will
      need to address the challenges raised by the application of next-generation
      sequencing in miRNA research.

PMID- 22403586
TI  - Kinase inhibitors in the treatment of immune-mediated disease.
AB  - Protein kinases are fundamental components of diverse signaling pathways,
      including immune cells. Their essential functions have made them effective
      therapeutic targets. Initially, the expectation was that a high degree of
      selectivity would be critical; however, with time, the use of "multikinase"
      inhibitors has expanded. Moreover, the spectrum of diseases in which kinase
      inhibitors are used has also expanded to include not only malignancies but also
      immune-mediated diseases. At present, thirteen kinase inhibitors have been
      approved in the United States, all for oncologic indications. However, there are
      a growing number of molecules, including several Janus kinase inhibitors, that
      are being tested in clinical trials for autoimmune diseases such as rheumatoid
      arthritis, psoriasis and inflammatory bowel diseases. It appears likely that this
      new class of immunomodulatory drugs will have a major impact on the treatment of
      immune-mediated diseases in the near future.

PMID- 22403587
TI  - Cognitive behaviour therapy for schizophrenia.
AB  - Schizophrenia is one of the major and potentially severe mental illnesses. Even
      with best practices, there are limitations to the effectiveness of treatments
      that include medications for this disorder. Relapse rates are high and often
      those with the illness remain symptomatic and functionally impaired. All the
      evidence suggests that individuals with schizophrenia do best with a combination
      of pharmacological and psychosocial intervention. One psychosocial treatment that
      has received much attention is cognitive behaviour therapy (CBT). This brief
      review will address what we know about the use and effectiveness of CBT at all
      phases of schizophrenia and its strengths, weaknesses and its future.

PMID- 22403588
TI  - New antiviral agents for hepatitis C.
AB  - Approximately 120-130 million individuals are chronically infected with hepatitis
      C virus (HCV) worldwide, although it is curable by therapy. Until recently,
      treatment of chronic hepatitis C was based on the combination of pegylated
      interferon-alpha and ribavirin. A number of models have been developed to study
      the HCV lifecycle and screen for potential HCV inhibitors. They led to the
      development of antiviral agents that specifically target a viral function (direct
      acting antivirals), and host-targeted agents that inhibit HCV replication. Direct
      acting antivirals in clinical development include NS3-4A protease inhibitors (two
      of which, telaprevir and boceprevir, have recently been approved for treatment of
      HCV genotype 1 infection in combination with pegylated interferon-alpha and
      ribavirin), nucleoside/nucleotide analogue and non-nucleoside inhibitors of HCV
      RNA-dependent RNA polymerase, and NS5A inhibitors. Host-targeted agents include
      cyclophilin inhibitors. This article describes the direct acting antivirals and
      host-targeted agents that have recently been approved or have been tested in HCV
      infected patients and discusses their two current paths of clinical development:
      with or without interferon-alpha.

PMID- 22403590
TI  - Patients, training hours and the number of places for studying medicine. A
      comment on new and old disagreements between AAppO and KapVO.

PMID- 22403589
TI  - Cellular networks controlling Th2 polarization in allergy and immunity.
AB  - In contrast to the development of Th1 (type 1 T helper cells), Th17 and Treg
      (regulatory T cells), little is known of the mechanisms governing Th2
      development, which is important for immunity to helminths and for us to
      understand the pathogenesis of allergy. A picture is emerging in which mucosal
      epithelial cells instruct dendritic cells to promote Th2 responses in the absence
      of IL-12 (interleukin 12) production and provide instruction through thymic
      stromal lymphopoieitin (TSLP) or granulocyte-macrophage colony stimulating factor
      (GM-CSF). At the same time, allergens, helminths and chemical adjuvants elicit
      the response of innate immune cells like basophils, which provide more polarizing
      cytokines and IL-4 and reinforce Th2 immunity. This unique communication between
      cells will only be fully appreciated if we study Th2 immunity in vivo and in a
      tissue-specific context, and can only be fully understood if we compare several
      models of Th2 immune response induction.

PMID- 22403591
TI  - Implementation of the interdisciplinary curriculum Teaching and Assessing
      Communicative Competence in the fourth academic year of medical studies (CoMeD).
AB  - INTRODUCTION: Implementation of a longitudinal curriculum for training in
      advanced communications skills represents an unmet need in most German medical
      faculties, especially in the 4rth and 5th years of medical studies. The CoMeD
      project (communication in medical education Dusseldorf) attempted to establish an
      interdisciplinary program to teach and to assess communicative competence in the
      4th academic year. In this paper, we describe the development of the project and
      report results of its evaluation by medical students. METHODS: Teaching
      objectives and lesson formats were developed in a multistage process. A teaching
      program for simulated patients (SP) was built up and continuous lecturer
      trainings were estabilshed. Several clinical disciplines co-operated for the
      purpose of integrating the communication training into the pre-existing clinical
      teaching curriculum. The CoMeD project was evaluated using feedback-forms after
      each course. RESULTS: Until now, six training units for especially challenging
      communication tasks like "dealing with aggression" or "breaking bad news" were
      implemented, each unit connected with a preliminary tutorial or e-learning
      course. An OSCE (objective structured clinical examination) with 4 stations was
      introduced. The students' evaluation of the six CoMeD training units showed the
      top or second-best rating in more than 80% of the answers. DISCUSSION:
      Introducing an interdisciplinary communication training and a corresponding OSCE
      into the 4th year medical curriculum is feasible. Embedding communication
      teaching in a clinical context and involvement of clinicians as lecturers seem to
      be important factors for ensuring practical relevance and achieving high
      acceptance by medical students.

PMID- 22403592
TI  - Differences between students and physicians in their entitlement towards
      procedural skills education--a needs assessment of skills training in internal
      medicine.
AB  - OBJECTIVE: Procedural skills education has a high priority for medical students.
      However, it is not clear what kind of skills they consider important and whether
      their perception differs from the physicians' view. METHODS: We conducted a
      survey on 26 skills in internal medicine among medical students and physicians.
      Ninety-five fourth year and 62 final year students along with 67 physicians
      working in medical departments participated in the survey. A similar but smaller
      survey was completed earlier before the implementation of a skills training at
      the faculty. RESULTS: Students generally preferred technically complex skills
      while, in contrast, physicians found "bed-side-skills" more important. The result
      was independent of the students' participation in the skills training or of the
      physicians' experience. A similar result was achieved in the smaller survey
      before the implementation of the skills training. CONCLUSION: Students and
      physicians significantly differ in their entitlement towards procedural skills
      education. This should be considered when educational strategies are being
      discussed.

PMID- 22403593
TI  - How important is medical ethics and history of medicine teaching in the medical
      curriculum? An empirical approach towards students' views.
AB  - OBJECTIVES: It was investigated how students judge the teaching of medical ethics
      and the history of medicine at the start and during their studies, and the
      influence which subject-specific teaching of the history, theory and ethics of
      medicine (GTE)--or the lack thereof--has on the judgement of these subjects.
      METHODS: From a total of 533 students who were in their first and 5th semester of
      the Bochum Model curriculum (GTE teaching from the first semester onwards) or
      followed the traditional curriculum (GTE teaching in the 5th/6th semester),
      questionnaires were requested in the winter semester 2005/06 and in the summer
      semester 2006. They were asked both before and after the 1st and 5th (model
      curriculum) or 6th semester (traditional curriculum). We asked students to judge
      the importance of teaching medical ethics and the history of medicine, the
      significance of these subjects for physicians and about teachability and
      testability (Likert scale from -2 (do not agree at all) to +2 (agree
      completely)). RESULTS: 331 questionnaire pairs were included in the study. There
      were no significant differences between the students of the two curricula at the
      start of the 1st semester. The views on medical ethics and the history of
      medicine, in contrast, were significantly different at the start of undergraduate
      studies: The importance of medical ethics for the individual and the physician
      was considered very high but their teachability and testability were rated
      considerably worse. For the history of medicine, the results were exactly
      opposite. GTE teaching led to a more positive assessment of items previously
      ranked less favourably in both curricula. A lack of teaching led to a drop in the
      assessment of both subjects which had previously been rated well. CONCLUSION:
      Consistent with the literature, our results support the hypothesis that the
      teaching of GTE has a positive impact on the views towards the history and ethics
      of medicine, with a lack of teaching having a negative impact. Therefore the
      teaching of GTE should already begin in the 1st semester. The teaching of GTE
      must take into account that even right at the start of their studies, students
      judge medical ethics and the history of medicine differently.

PMID- 22403594
TI  - Integration of an Objective Structured Clinical Examination (OSCE) into the
      dental preliminary exams.
AB  - INTRODUCTION: In the pre-clinical phase of the study of dentistry at the
      University of Greifswald, the course "Early Patient Contact (EPC)" is conducted
      within the framework of Community Medicine/Dentistry. The course is based on
      three pillars: the patient visiting program, special problem-oriented seminars,
      and communication training for doctors. The essential goal consists of providing
      students with real patient contact right at the beginning of their study of
      dentistry, thus making the study of dentistry patient-based very early on.
      Students are trained in taking comprehensive anamneses and recording clinical
      findings. METHODS: Within the framework of the dental preliminary exams, the
      course is evaluated using an OSCE on a standardized patient. Furthermore, the
      added value of an additional training unit (conducting anamnesis and clinical
      examination) in preparation for the OSCE was evaluated. The exam results of a
      group without training (control group) were compared with those of a group with
      training (intervention group). RESULTS: The intervention group performed
      significantly better than the control on the following items: the total number of
      points achieved on the OSCE early patient contact, and in the most important
      points of the anamnesis and clinical examination. In addition, the intervention
      group tended to score higher in terms of the item "oral health status".
      CONCLUSION: The present study showed a positive effect of an additional training
      unit on students' performance in the OSCE. Taking the limitations of the study
      and the results of a literature review into account, we recommend conducting such
      training as preparation for the OSCE.

PMID- 22403595
TI  - Burnout, depression and depersonalisation--psychological factors and coping
      strategies in dental and medical students.
AB  - BACKGROUND: Previous studies found that stress, depression, burnout, anxiety, and
      depersonalisation play a significant role amongst dental and medical students. We
      wanted to examine if students of the University of Erlangen-Nuremberg also would
      report elevated values as can been found in similar publications. Furthermore,
      particularly coping strategies were investigated. METHODS: The data collection
      took place in April 2008 including 182 dental and medical students of the 4th and
      5th academic year at the University of Erlangen-Nuremberg. Demographic data and
      the following screening instruments were used: Maslach Burnout Inventory (MBI),
      Cambridge Depersonalisation Scale (CDS-9), Hospital Anxiety and Depression Scale
      (HADS), Brief COPE. RESULTS: Descriptive statistics showed higher pathological
      values in dental students than in medical students. The difference was especially
      pronounced on the depersonalisation scale (CDS-9), with 20.4% of the dental
      students, but only 5.5% of the medical students showing scores above a cut-off of
      19. The scores decreased in the course of 3 semesters of dentistry. The students
      with elevated values showed a higher degree of dysfunctional coping. CONCLUSION:
      Our results obtained with the screening instruments are in line with the results
      of previous investigations of other authors and point out the importance of this
      issue. It might be useful to develop programs teaching dental students more
      adaptive coping strategies before their first patient contact.

PMID- 22403596
TI  - Physician empathy: definition, outcome-relevance and its measurement in patient
      care and medical education.
AB  - OBJECTIVE: The present study gives a brief introduction into 1. the definition of
      physician empathy (PE) and 2. its influence on patients' health outcomes.
      Furthermore 3. we present assessment instruments to measure PE from the
      perspective of the patient and medical student. The latter topic will be explored
      in detail as we conducted a pilot study on the German versions of two self
      assessment instruments of empathy, which are mostly used in medical education
      research, namely the "Jefferson Scale of Physician Empathy, Student Version"
      (JSPE-S) and the "Interpersonal Reactivity Index" (IRI). METHODS: We first
      present an overview of the current empirical and theoretical literature on the
      definition and outcome-relevance of PE. Additionally, we conducted basic
      psychometric analyses of the German versions of the JSPE-S and the IRI. Data for
      this analyses is based on a cross-sectional pilot-survey in N=44 medical students
      and N=63 students of other disciplines from the University of Cologne. RESULTS:
      PE includes the understanding of the patient as well as verbal and non-verbal
      communication, which should result in a helpful therapeutic action of the
      physician. Patients' health outcomes in different healthcare settings can be
      improved considerably from a high quality empathic encounter with their
      clinician. Basic psychometric results of the German JSPE-S and IRI measures show
      first promising results. CONCLUSION: PE as an essential and outcome-relevant
      element in the patient-physician relationship requires more consideration in the
      education of medical students and, thus, in medical education research. The
      German versions of the JSPE-S and IRI measures seem to be promising means to
      evaluate these education aims and to conduct medical education research on
      empathy.

PMID- 22403597
TI  - Psychological stress in first year medical students in response to the dissection
      of a human corpse.
AB  - OBJECTIVES: Gross anatomy is one of the most important and time consuming
      subjects in the first preclinical part of medical school in Germany. In October
      2007 186 students started the dissection course at Otto-von-Guericke-University
      Magdeburg. The objective of this study is to analyze the emotional aspect
      relating to the gross anatomy course. In order to address this issue, we
      investigated how medical students experience the first confrontation and the
      following exposure to the dead bodies and whether there are any differences
      between various groups (age, gender, experience) of students. METHODS: The study
      was carried out with a group of 155 first year medical students (112 female, 43
      male, 21.4+/-2.9 years). Self-composed questionnaires were used to distinguish
      between concerns related to dissection and individual experiences and anxiety
      because of deceasing or death. In order to detect the changes of attitudes
      towards the dissection course, one questionnaire was answered by participants in
      the beginning of the course and one in the end (n=94, 66 female, 28 male).
      Additionally, personality traits of the students were analyzed using two scales
      of the "Freiburger Personlichkeitsinventar (FPI-R)". RESULTS: The self-composed
      questionnaires showed high reliability. For some students dissection was
      emotional stress; about 50% became anxious when coping the first confrontation,
      however, only 12% to large extent. Concerning the anxiety of dissection of
      individual body parts it was less for limbs, internal organs and skin and
      increased for head and genitals. Although hypothesized before, the correlation
      between age, extraversion, emotionality and the extent of anxiety were small.
      Almost 90% of the students approve the early beginning of the gross anatomy
      course. The follow-up study showed a marked decline of anxiety. CONCLUSION: Our
      results show that about 50% of the students started the course with emotional
      stress and about one-tenth of them were very worried about the confrontation with
      corpses. Furthermore, personality tests were shown to be only partly reliable for
      selecting affected people in advance. With regard to these results capabilities
      to provide support to the first year medical students should be discussed.

PMID- 22403598
TI  - Integrating patients into medical education.
AB  - The discussions about medical education in the public focus upon quantity. The
      quality of the teaching process isn't questioned. But the professionalization of
      medical education should start with a close look at bedside teaching because it
      is the core of training medical doctors. PATIENT-CENTERED TEACHING: German
      medical leicensure act (Approbationsordnung) defines the quality of medical
      education by standard setting for group sizes and fixing the hours of bedside
      teaching. Although there are some fuzzy definitions it is possible to extract
      some special forms of bedside teaching. The capacity act (Kapazitatsverordnung)
      interprets these definitions for calculating the number of students who could be
      enrolled each year. TYPES OF BEDSIDE TEACHING: The different forms of contact
      with patients which are necessary for a good medical education can be transformed
      into distinct types of courses. Our classification of courses with specific forms
      of patient contact is suitable to describe each German program of medical
      studies. This quantitative profile offers new opportunities for comparing medical
      education at the different faculties. DISCUSSION: In many German medical schools
      the hours of bedside teaching are allocated in a verv pragmatical way according
      to the medical leicensure act. A more professional curriculum planning leads to a
      sophisticated use of these diverse forms of patient-centered teaching. Because
      this professional planning is better derived from the legal basis it offers new
      arguments against an economically oriented hospital management.

PMID- 22403603
TI  - Differential, phosphorylation dependent trafficking of AQP2 in LLC-PK1 cells.
AB  - The kidney maintains water homeostasis by modulating aquaporin 2 (AQP2) on the
      plasma membrane of collecting duct principal cells in response to vasopressin
      (VP). VP mediated phosphorylation of AQP2 at serine 256 is critical for this
      effect. However, the role of phosphorylation of other serine residues in the AQP2
      C-terminus is less well understood. Here, we examined the effect of
      phosphorylation of S256, S261 and S269 on AQP2 trafficking and association with
      recycling pathway markers. We used LLC-PK1 cells expressing AQP2(S-D) or (S-A)
      phospho mutants and a 20 degrees C cold block, which allows endocytosis to
      continue, but prevents protein exit from the trans Golgi network (TGN), inducing
      formation of a perinuclear AQP2 patch. AQP2-S256D persists on the plasma membrane
      during cold block, while wild type AQP2, AQP2-S256A, S261A, S269A and S269D are
      internalized and accumulate in the patch. Development of this patch, a measure of
      AQP2 internalization, was most rapid with AQP2-S256A, and slowest with S261A and
      S269D. AQP2-S269D exhibited a biphasic internalization profile with a significant
      amount not internalized until 150 minutes of cold block. After rewarming to 37
      degrees C, wt AQP2, AQP2-S261A and AQP2-S269D rapidly redistributed throughout
      the cytoplasm within 20 minutes, whereas AQP2-S256A dissipated more slowly.
      Colocalization of AQP2 mutants with several key vesicular markers including
      clathrin, HSP70/HSC70, EEA, GM130 and Rab11 revealed no major differences.
      Overall, our data provide evidence supporting the role of S256 and S269 in the
      maintenance of AQP2 at the cell surface and reveal the dynamics of
      internalization and recycling of differentially phosphorylated AQP2 in cell
      culture.

PMID- 22403604
TI  - Adverse drug reactions in children--a systematic review.
AB  - BACKGROUND: Adverse drug reactions in children are an important public health
      problem. We have undertaken a systematic review of observational studies in
      children in three settings: causing admission to hospital, occurring during
      hospital stay and occurring in the community. We were particularly interested in
      understanding how ADRs might be better detected, assessed and avoided. METHODS
      AND FINDINGS: We searched nineteen electronic databases using a comprehensive
      search strategy. In total, 102 studies were included. The primary outcome was any
      clinical event described as an adverse drug reaction to one or more drugs.
      Additional information relating to the ADR was collected: associated drug
      classification; clinical presentation; associated risk factors; methods used for
      assessing causality, severity, and avoidability. Seventy one percent (72/102) of
      studies assessed causality, and thirty four percent (34/102) performed a severity
      assessment. Only nineteen studies (19%) assessed avoidability. Incidence rates
      for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children
      (pooled estimate of 2.9% (2.6%, 3.1%)) and from 0.6% to 16.8% of all children
      exposed to a drug during hospital stay. Anti-infectives and anti-epileptics were
      the most frequently reported therapeutic class associated with ADRs in children
      admitted to hospital (17 studies; 12 studies respectively) and children in
      hospital (24 studies; 14 studies respectively), while anti-infectives and non
      steroidal anti-inflammatory drugs (NSAIDs) were frequently reported as associated
      with ADRs in outpatient children (13 studies; 6 studies respectively). Fourteen
      studies reported rates ranging from 7%-98% of ADRs being either
      definitely/possibly avoidable. CONCLUSIONS: There is extensive literature which
      investigates ADRs in children. Although these studies provide estimates of
      incidence in different settings and some indication of the therapeutic classes
      most frequently associated with ADRs, further work is needed to address how such
      ADRs may be prevented.

PMID- 22403605
TI  - Fetal outcomes in pregnancies complicated by intrahepatic cholestasis of
      pregnancy in a Northern California cohort.
AB  - BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) has important fetal
      implications. There is increased risk for poor fetal outcomes, including preterm
      delivery, meconium staining of amniotic fluid, respiratory distress, fetal
      distress and demise. METHODS: One hundred and one women diagnosed with ICP
      between January 2005 and March 2009 at San Francisco General Hospital were
      included in this study. Single predictor logistic regression models were used to
      assess the associations of maternal clinical and biochemical predictors with
      fetal complications. Clinical predictors analyzed included age, race/ethnicity,
      gravidity, parity, history of liver or biliary disease, history of ICP in
      previous pregnancies, and induction. Biochemical predictors analyzed included
      serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase,
      total bilirubin, direct bilirubin, albumin, total protein, and total bile acids
      (TBA). RESULTS: The prevalence of ICP was 1.9%. Most were Latina (90%). Labor was
      induced in the majority (87%) and most were delivered by normal spontaneous
      vaginal delivery (84%). Fetal complications occurred in 33% of the deliveries,
      with respiratory distress accounting for the majority of complications. There
      were no statistically significant clinical or biochemical predictors associated
      with an increased risk of fetal complications. Elevated TBA had little
      association with fetal complications until reaching greater than 100 umoL/L, with
      3 out of 5 having reported complications. ICP in previous pregnancies was
      associated with decreased risk of fetal complications (OR 0.21, p = 0.046). There
      were no cases of late term fetal demise. CONCLUSIONS: Maternal clinical and
      laboratory features, including elevated TBA, did not appear to be substantial
      predictors of fetal complications in ICP.

PMID- 22403606
TI  - Stress system dynamics during "life as it is lived": an integrative single-case
      study on a healthy woman.
AB  - Little is known about the dynamic characteristics of stress system activity
      during "life as it is lived". Using as representative a study design as possible,
      this investigation sought to gain insights into this area. A healthy 25-year-old
      woman collected her entire urine over a period of 63 days in 12-h intervals (126
      measurements) to determine cortisol and neopterin (immune activation marker)
      levels. In addition, she filled out questionnaires on emotional state and daily
      routine in 12-h intervals, and was interviewed weekly to identify emotionally
      negative and positive everyday incidents. Adjusted cross-correlational analyses
      revealed that stressful incidents were associated with cyclic response patterns
      in both urinary cortisol and urinary neopterin concentrations. Urinary cortisol
      levels first decreased 12-24 h after stressful incidents occurred (lag 1: -.178;
      p = 0.048) and then increased a total of 72-84 h later (lag 6: +.224; p = 0.013).
      Urinary neopterin levels first increased 0-12 h before the occurrence of
      stressful incidents (-lag 1: +.185; p = 0.040) and then decreased a total of 48
      60 h following such stressors (lag 4: -.181; p = 0.044). Decreases in urinary
      neopterin levels were also found 24-36 and 48-60 h after increases in pensiveness
      (lag 2: -.215; p = 0.017) and depressiveness (lag 4: -.221; p = 0.014),
      respectively. Findings on emotionally positive incidents sharply contrasted with
      those dealing with negative experiences. Positive incidents were followed first
      by urinary cortisol concentration increases within 12 h (lag 0: +.290; p = 0.001)
      and then by decreases after a total of 60-72 h (lag 5: -.186; p = 0.039). Urinary
      neopterin levels first decreased 12-24 h before positive incidents occurred (-lag
      2: -.233; p = 0.010) and then increased a total of 12-24 h following these
      incidents (lag 1: +.222; p = 0.014). As with previous investigations on patients
      with systemic lupus erythematosus (SLE), this study showed that stress system
      response can be considerably longer and more complex and differentiated than
      findings from conventional group studies have suggested. Further integrative
      single-case studies will need to be conducted in order to draw firm conclusions
      about stress system dynamics under real-life conditions.

PMID- 22403607
TI  - Unsupervised analysis of classical biomedical markers: robustness and medical
      relevance of patient clustering using bioinformatics tools.
AB  - MOTIVATION: It has been proposed that clustering clinical markers, such as blood
      test results, can be used to stratify patients. However, the robustness of
      clusters formed with this approach to data pre-processing and clustering
      algorithm choices has not been evaluated, nor has clustering reproducibility.
      Here, we made use of the NHANES survey to compare clusters generated with various
      combinations of pre-processing and clustering algorithms, and tested their
      reproducibility in two separate samples. METHOD: Values of 44 biomarkers and 19
      health/life style traits were extracted from the National Health and Nutrition
      Examination Survey (NHANES). The 1999-2002 survey was used for training, while
      data from the 2003-2006 survey was tested as a validation set. Twelve
      combinations of pre-processing and clustering algorithms were applied to the
      training set. The quality of the resulting clusters was evaluated both by
      considering their properties and by comparative enrichment analysis. Cluster
      assignments were projected to the validation set (using an artificial neural
      network) and enrichment in health/life style traits in the resulting clusters was
      compared to the clusters generated from the original training set. RESULTS: The
      clusters obtained with different pre-processing and clustering combinations
      differed both in terms of cluster quality measures and in terms of
      reproducibility of enrichment with health/life style properties. Z-score
      normalization, for example, dramatically improved cluster quality and
      enrichments, as compared to unprocessed data, regardless of the clustering
      algorithm used. Clustering diabetes patients revealed a group of patients
      enriched with retinopathies. This could indicate that routine laboratory tests
      can be used to detect patients suffering from complications of diabetes, although
      other explanations for this observation should also be considered. CONCLUSIONS:
      Clustering according to classical clinical biomarkers is a robust process, which
      may help in patient stratification. However, optimization of the pre-processing
      and clustering process may be still required.

PMID- 22403608
TI  - Effects of deletion of macrophage ABCA7 on lipid metabolism and the development
      of atherosclerosis in the presence and absence of ABCA1.
AB  - ABCA7, a close relative of ABCA1 which facilitates cholesterol efflux to lipid
      poor apoproteins, has been implicated in macrophage lipid efflux and clearance of
      apoptotic cells in in vitro studies. In the current study, we investigated the in
      vivo effects of macrophage ABCA7 deficiency on lipid metabolism and
      atherosclerosis. Chimeras with dysfunctional ABCA7 in macrophages and other blood
      cells were generated by transplantation of bone marrow from ABCA7 knockout (KO)
      mice into irradiated low-density lipoprotein receptor (LDLr) KO mice.
      Unexpectedly, macrophage ABCA7 deficiency did not significantly affect
      atherosclerosis susceptibility of LDLr KO mice after 10 weeks Western-type diet
      feeding. However, ABCA7 deficiency was associated with 2-fold (p<0.05) higher
      macrophage ABCA1 mRNA expression levels. Combined disruption of ABCA1 and ABCA7
      in bone-marrow-derived cells increased atherosclerotic lesion development (1.5
      fold (p>0.05) as compared to wild type transplanted mice. However, single
      deletion of ABCA1 had a similar effect (1.8-fold, p<0.05). Macrophage foam cell
      accumulation in the peritoneal cavity was reduced in ABCA1/ABCA7 dKO transplanted
      animals as compared to single ABCA1 KO transplanted mice, which was associated
      with increased ABCG1 expression. Interestingly, spleens of ABCA1/ABCA7 double KO
      transplanted mice were significantly larger as compared to the other 3 groups and
      showed massive macrophage lipid accumulation, a reduction in CD3+ T-cells, and
      increased expression of key regulators of erythropoiesis. In conclusion, deletion
      of ABCA7 in bone marrow-derived cells does not affect atherogenesis in the
      arterial wall neither in the absence or presence of ABCA1. Interestingly,
      combined deletion of bone marrow ABCA1 and ABCA7 causes severe splenomegaly
      associated with cellular lipid accumulation, a reduction in splenic CD3+ T cells,
      and induced markers of erythropoeisis. Our data indicate that ABCA7 may play a
      role in T cell proliferation and erythropoeisis in spleen.

PMID- 22403609
TI  - Androgen receptor drives cellular senescence.
AB  - The accepted androgen receptor (AR) role is to promote proliferation and survival
      of prostate epithelium and thus prostate cancer progression. While growth
      inhibitory, tumor-suppressive AR effects have also been documented, the
      underlying mechanisms are poorly understood. Here, we for the first time link AR
      anti-cancer action with cell senescence in vitro and in vivo. First, AR-driven
      senescence was p53-independent. Instead, AR induced p21, which subsequently
      reduced DeltaN isoform of p63. Second, AR activation increased reactive oxygen
      species (ROS) and thereby suppressed Rb phosphorylation. Both pathways were
      critical for senescence as was proven by p21 and Rb knock-down and by quenching
      ROS with N-Acetyl cysteine and p63 silencing also mimicked AR-induced senescence.
      The two pathways engaged in a cross-talk, likely via PML tumor suppressor, whose
      localization to senescence-associated chromatin foci was increased by AR
      activation. All these pathways contributed to growth arrest, which resolved in
      senescence due to concomitant lack of p53 and high mTOR activity. This is the
      first demonstration of senescence response caused by a nuclear hormone receptor.

PMID- 22403611
TI  - Informatics enhanced SNP microarray analysis of 30 miscarriage samples compared
      to routine cytogenetics.
AB  - PURPOSE: The metaphase karyotype is often used as a diagnostic tool in the
      setting of early miscarriage; however this technique has several limitations. We
      evaluate a new technique for karyotyping that uses single nucleotide polymorphism
      microarrays (SNP). This technique was compared in a blinded, prospective fashion,
      to the traditional metaphase karyotype. METHODS: Patients undergoing dilation and
      curettage for first trimester miscarriage between February and August 2010 were
      enrolled. Samples of chorionic villi were equally divided and sent for microarray
      testing in parallel with routine cytogenetic testing. RESULTS: Thirty samples
      were analyzed, with only four discordant results. Discordant results occurred
      when the entire genome was duplicated or when a balanced rearrangement was
      present. Cytogenetic karyotyping took an average of 29 days while microarray
      based karytoyping took an average of 12 days. CONCLUSIONS: Molecular karyotyping
      of POC after missed abortion using SNP microarray analysis allows for the ability
      to detect maternal cell contamination and provides rapid results with good
      concordance to standard cytogenetic analysis.

PMID- 22403610
TI  - ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell
      growth.
AB  - Receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) is expressed during
      embryogenesis and by certain leukemias, but not by normal adult tissues. Here we
      show that the neoplastic cells of many human breast cancers express the ROR1
      protein and high-level expression of ROR1 in breast adenocarcinoma was associated
      with aggressive disease. Silencing expression of ROR1 in human breast cancer cell
      lines found to express this protein impaired their growth in vitro and also in
      immune-deficient mice. We found that ROR1 could interact with casein kinase 1
      epsilon (CK1epsilon) to activate phosphoinositide 3-kinase-mediated AKT
      phosphorylation and cAMP-response-element-binding protein (CREB), which was
      associated with enhanced tumor-cell growth. Wnt5a, a ligand of ROR1, could induce
      ROR1-dependent signaling and enhance cell growth. This study demonstrates that
      ROR1 is expressed in human breast cancers and has biological and clinical
      significance, indicating that it may be a potential target for breast cancer
      therapy.

PMID- 22403612
TI  - Selective loss of chemokine receptor expression on leukocytes after cell
      isolation.
AB  - Chemokine receptors are distinctively exposed on cells to characterize their
      migration pattern. However, little is known about factors that may regulate their
      expression. To determine the optimal conditions for an accurate analysis of
      chemokine receptors, we compared the expression of CCR2, CCR4, CCR5, CCR6, CXCR3
      and CXCR4 on different leukocyte subsets using whole blood (WB) plus erythrocyte
      lysis and density gradient isolation (Ficoll). Most WB monocytes were CCR2+ (93.5
      +/- 2.9%) whereas 32.8 +/- 6.0% of monocytes from Ficoll-PBMC expressed CCR2
      (p<0.001). Significant reductions of CCR6 and CXCR3 on monocytes were also
      observed after Ficoll isolation (WB: 46.4 +/- 7.5% and 57.1 +/- 5.5%; Ficoll:
      29.5 +/- 2.2% and 5.4 +/- 4.3% respectively) (p<0.01). Although comparable
      percentages of WB and Ficoll-PBMC monocytes expressed CCR4, CCR5 and CXCR4,
      Ficoll isolation significantly reduced the levels of CXCR4 (WB: MFI 5 +/- 0.4 and
      Ficoll: MFI 3.3 +/- 0.1) (p<0.05). Similarly to monocytes, CCR2, CXCR3 and CXCR4
      were also reduced on lymphocytes. In addition, Ficoll isolation significantly
      reduced the percentage of CCR4 positive lymphocytes (WB: 90.2 +/- 4.5% and
      Ficoll: 55 +/- 4.1%) (p<0.01). The loss of expression of chemokine receptors
      after isolation of monocytes was not dependent on either the anticoagulant or the
      density gradient method. It was irreversible and could not be restored by LPS
      activation or in vitro macrophage differentiation. Experiments tagged with anti
      CCR2 antibodies prior to density gradient isolation demonstrated that Ficoll
      internalized chemokine receptors. The method for cell isolation may alter not
      only the expression of certain chemokine receptors but also the respective
      functional migration assay. The final choice to analyze their expression should
      therefore depend on the receptor to be measured.

PMID- 22403614
TI  - The highly virulent 2006 Norwegian EHEC O103:H25 outbreak strain is related to
      the 2011 German O104:H4 outbreak strain.
AB  - In 2006, a severe foodborne EHEC outbreak occured in Norway. Seventeen cases were
      recorded and the HUS frequency was 60%. The causative strain, Esherichia coli
      O103:H25, is considered to be particularly virulent. Sequencing of the outbreak
      strain revealed resemblance to the 2011 German outbreak strain E. coli O104:H4,
      both in genome and Shiga toxin 2-encoding (Stx2) phage sequence. The nucleotide
      identity between the Stx2 phages from the Norwegian and German outbreak strains
      was 90%. During the 2006 outbreak, stx(2)-positive O103:H25 E. coli was isolated
      from two patients. All the other outbreak associated isolates, including all food
      isolates, were stx-negative, and carried a different phage replacing the Stx2
      phage. This phage was of similar size to the Stx2 phage, but had a distinctive
      early phage region and no stx gene. The sequence of the early region of this
      phage was not retrieved from the bacterial host genome, and the origin of the
      phage is unknown. The contaminated food most likely contained a mixture of E.
      coli O103:H25 cells with either one of the phages.

PMID- 22403613
TI  - Common genetic variations in the NALP3 inflammasome are associated with delayed
      apoptosis of human neutrophils.
AB  - BACKGROUND: Neutrophils are key-players in the innate host defense and their
      programmed cell death and removal are essential for efficient resolution of
      inflammation. These cells recognize a variety of pathogens, and the NOD-like
      receptors (NLRs) have been suggested as intracellular sensors of microbial
      components and cell injury/stress. Some NLR will upon activation form multi
      protein complexes termed inflammasomes that result in IL-1beta production. NLR
      mutations are associated with auto-inflammatory syndromes, and our previous data
      propose NLRP3 (Q705K)/CARD-8 (C10X) polymorphisms to contribute to increased risk
      and severity of inflammatory disease by acting as genetic susceptibility factors.
      These gene products are components of the NALP3 inflammasome, and approximately
      6.5% of the Swedish population are heterozygote carriers of these combined gene
      variants. Since patients carrying the Q705K/C10X polymorphisms display
      leukocytosis, the aim of the present study was to find out whether the
      inflammatory phenotype was related to dysfunctional apoptosis and impaired
      clearance of neutrophils by macrophages. METHODS AND FINDINGS: Patients carrying
      the Q705K/C10X polymorphisms displayed significantly delayed spontaneous as well
      as microbe-induced apoptosis compared to matched controls. Western blotting
      revealed increased levels and phosphorylation of Akt and Mcl-1 in the patients'
      neutrophils. In contrast to macrophages from healthy controls, macrophages from
      the patients produced lower amounts of TNF; suggesting impaired macrophage
      clearance response. CONCLUSIONS: The Q705K/C10X polymorphisms are associated with
      delayed apoptosis of neutrophils. These findings are explained by altered
      involvement of different regulators of apoptosis, resulting in an anti-apoptotic
      profile. Moreover, the macrophage response to ingestion of microbe-induced
      apoptotic neutrophils is altered in the patients. Taken together, the patients
      display impaired turnover and clearance of apoptotic neutrophils, pointing
      towards a dysregulated innate immune response that influences the resolution of
      inflammation. The future challenge is to understand how microbes affect the
      activation of inflammasomes, and why this interaction will develop into severe
      inflammatory disease in certain individuals.

PMID- 22403615
TI  - Identification, purification and characterization of laterosporulin, a novel
      bacteriocin produced by Brevibacillus sp. strain GI-9.
AB  - BACKGROUND: Bacteriocins are antimicrobial peptides that are produced by bacteria
      as a defense mechanism in complex environments. Identification and
      characterization of novel bacteriocins in novel strains of bacteria is one of the
      important fields in bacteriology. METHODOLOGY/FINDINGS: The strain GI-9 was
      identified as Brevibacillus sp. by 16 S rRNA gene sequence analysis. The
      bacteriocin produced by strain GI-9, namely, laterosporulin was purified from
      supernatant of the culture grown under optimal conditions using hydrophobic
      interaction chromatography and reverse-phase HPLC. The bacteriocin was active
      against a wide range of Gram-positive and Gram-negative bacteria. MALDI-TOF
      experiments determined the precise molecular mass of the peptide to be of 5.6 kDa
      and N-terminal sequencing of the thermo-stable peptide revealed low similarity
      with existing antimicrobial peptides. The putative open reading frame (ORF)
      encoding laterosporulin and its surrounding genomic region was fished out from
      the draft genome sequence of GI-9. Sequence analysis of the putative bacteriocin
      gene did not show significant similarity to any reported bacteriocin producing
      genes in database. CONCLUSIONS: We have identified a bacteriocin producing strain
      GI-9, belonging to the genus Brevibacillus sp. Biochemical and genomic
      characterization of laterosporulin suggests it as a novel bacteriocin with broad
      spectrum antibacterial activity.

PMID- 22403616
TI  - XIAP is a predictor of cisplatin-based chemotherapy response and prognosis for
      patients with advanced head and neck cancer.
AB  - BACKGROUND: Approximately 60-80% of patients with advanced head and neck squamous
      cell carcinoma (HNSCC) die within five years after diagnosis. Cisplatin-based
      chemotherapy is the most commonly used palliative treatment for these patients.
      To evaluate the prognostic value of X-linked inhibitor of apoptosis (XIAP) level
      as a potential biomarker in these patients, we investigated the relationship
      between XIAP expression and cisplatin response of these patients and their
      prognosis. METHODOLOGY/PRINCIPAL FINDINGS: Sixty patients with advanced HNSCC
      were recruited in this study. Expression of XIAP was examined both before and
      after chemotherapy and was correlated with chemotherapy response,
      clinicopathology parameters and clinical outcomes of the patients. We found that
      XIAP was expressed in 17 (20.83%) of the 60 advanced HNSCC samples and the
      expression was significantly associated with cisplatin resistance (P = 0.036) and
      poor clinical outcome (P = 0.025). Cisplatin-based chemotherapy induced XIAP
      expression in those post-chemotherapy samples (P = 0.011), was further associated
      with poorer clinical outcome (P = 0.029). Multivariate analysis demonstrated that
      only alcohol consumption, lymph node metastasis and XIAP level were independently
      associated with the prognosis of advanced HNSCC patients. Inhibiting XIAP
      expression with siRNA in XIAP overexpressed HNSCC cells remarkably increased
      their sensitivity to cisplatin treatment to nearly a 3 fold difference.
      CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that XIAP overexpression plays
      an important role in the disease course and cisplatin-resistance of advanced
      HNSCC. XIAP is a valuable predictor of cisplatin-response and prognosis for
      patients with advanced head and neck cancer. Down-regulation of XIAP might be a
      promising adjuvant therapy for those patients of advanced HNSCC.

PMID- 22403617
TI  - Detecting remote sequence homology in disordered proteins: discovery of conserved
      motifs in the N-termini of Mononegavirales phosphoproteins.
AB  - Paramyxovirinae are a large group of viruses that includes measles virus and
      parainfluenza viruses. The viral Phosphoprotein (P) plays a central role in viral
      replication. It is composed of a highly variable, disordered N-terminus and a
      conserved C-terminus. A second viral protein alternatively expressed, the V
      protein, also contains the N-terminus of P, fused to a zinc finger. We suspected
      that, despite their high variability, the N-termini of P/V might all be
      homologous; however, using standard approaches, we could previously identify
      sequence conservation only in some Paramyxovirinae. We now compared the N-termini
      using sensitive sequence similarity search programs, able to detect residual
      similarities unnoticeable by conventional approaches. We discovered that all
      Paramyxovirinae share a short sequence motif in their first 40 amino acids, which
      we called soyuz1. Despite its short length (11-16aa), several arguments allow us
      to conclude that soyuz1 probably evolved by homologous descent, unlike linear
      motifs. Conservation across such evolutionary distances suggests that soyuz1
      plays a crucial role and experimental data suggest that it binds the viral
      nucleoprotein to prevent its illegitimate self-assembly. In some Paramyxovirinae,
      the N-terminus of P/V contains a second motif, soyuz2, which might play a role in
      blocking interferon signaling. Finally, we discovered that the P of related
      Mononegavirales contain similarly overlooked motifs in their N-termini, and that
      their C-termini share a previously unnoticed structural similarity suggesting a
      common origin. Our results suggest several testable hypotheses regarding the
      replication of Mononegavirales and suggest that disordered regions with little
      overall sequence similarity, common in viral and eukaryotic proteins, might
      contain currently overlooked motifs (intermediate in length between linear motifs
      and disordered domains) that could be detected simply by comparing orthologous
      proteins.

PMID- 22403618
TI  - Differential expression of iron acquisition genes by Brucella melitensis and
      Brucella canis during macrophage infection.
AB  - Brucella spp. cause chronic zoonotic disease often affecting individuals and
      animals in impoverished economic or public health conditions; however, these
      bacteria do not have obvious virulence factors. Restriction of iron availability
      to pathogens is an effective strategy of host defense. For brucellae, virulence
      depends on the ability to survive and replicate within the host cell where iron
      is an essential nutrient for the growth and survival of both mammalian and
      bacterial cells. Iron is a particularly scarce nutrient for bacteria with an
      intracellular lifestyle. Brucella melitensis and Brucella canis share ~99% of
      their genomes but differ in intracellular lifestyles. To identify differences,
      gene transcription of these two pathogens was examined during infection of murine
      macrophages and compared to broth grown bacteria. Transcriptome analysis of B.
      melitensis and B. canis revealed differences of genes involved in iron transport.
      Gene transcription of the TonB, enterobactin, and ferric anguibactin transport
      systems was increased in B. canis but not B. melitensis during infection of
      macrophages. The data suggest differences in iron requirements that may
      contribute to differences observed in the lifestyles of these closely related
      pathogens. The initial importance of iron for B. canis but not for B. melitensis
      helps elucidate differing intracellular survival strategies for two closely
      related bacteria and provides insight for controlling these pathogens.

PMID- 22403619
TI  - Molecular interpretation of ACTH-beta-endorphin coaggregation: relevance to
      secretory granule biogenesis.
AB  - Peptide/protein hormones could be stored as non-toxic amyloid-like structures in
      pituitary secretory granules. ACTH and beta-endorphin are two of the important
      peptide hormones that get co-stored in the pituitary secretory granules. Here, we
      study molecular interactions between ACTH and beta-endorphin and their
      colocalization in the form of amyloid aggregates. Although ACTH is known to be a
      part of ACTH-beta-endorphin aggregate, ACTH alone cannot aggregate into amyloid
      under various plausible conditions. Using all atom molecular dynamics simulation
      we investigate the early molecular interaction events in the ACTH-beta-endorphin
      system, beta-endorphin-only system and ACTH-only system. We find that beta
      endorphin and ACTH formed an interacting unit, whereas negligible interactions
      were observed between ACTH molecules in ACTH-only system. Our data suggest that
      ACTH is not only involved in interaction with beta-endorphin but also enhances
      the stability of mixed oligomers of the entire system.

PMID- 22403620
TI  - Cholesteryl Ester Transfer Protein (CETP) polymorphisms affect mRNA splicing, HDL
      levels, and sex-dependent cardiovascular risk.
AB  - Polymorphisms in and around the Cholesteryl Ester Transfer Protein (CETP) gene
      have been associated with HDL levels, risk for coronary artery disease (CAD), and
      response to therapy. The mechanism of action of these polymorphisms has yet to be
      defined. We used mRNA allelic expression and splice isoform measurements in human
      liver tissues to identify the genetic variants affecting CETP levels. Allelic
      CETP mRNA expression ratios in 56 human livers were strongly associated with
      several variants 2.5-7 kb upstream of the transcription start site (e.g.,
      rs247616 p = 6.4 * 10(-5), allele frequency 33%). In addition, a common
      alternatively spliced CETP isoform lacking exon 9 (Delta9), has been shown to
      prevent CETP secretion in a dominant-negative manner. The Delta 9 expression
      ranged from 10 to 48% of total CETP mRNA in 94 livers. Increased formation of
      this isoform was exclusively associated with an exon 9 polymorphism rs5883-C>T (p
      = 6.8 * 10(-10)) and intron 8 polymorphism rs9930761-T>C (5.6 * 10(-8)) (in high
      linkage disequilibrium with allele frequencies 6-7%). rs9930761 changes a key
      splicing branch point nucleotide in intron 8, while rs5883 alters an exonic
      splicing enhancer sequence in exon 9.The effect of these polymorphisms was
      evaluated in two clinical studies. In the Whitehall II study of 4745 subjects,
      both rs247616 and rs5883T/rs9930761C were independently associated with increased
      HDL-C levels in males with similar effect size (rs247616 p = 9.6 * 10(-28) and
      rs5883 p = 8.6 * 10(-10), adjusted for rs247616). In an independent multiethnic
      US cohort of hypertensive subjects with CAD (INVEST-GENE), rs5883T/rs9930761C
      alone were significantly associated with increased incidence of MI, stroke, and
      all-cause mortality in males (rs5883: OR 2.36 (CI 1.29-4.30), p = 0.005, n =
      866). These variants did not reach significance in females in either study.
      Similar to earlier results linking low CETP activity with poor outcomes in males,
      our results suggest genetic, sex-dependent CETP splicing effects on
      cardiovascular risk by a mechanism independent of circulating HDL-C levels.

PMID- 22403621
TI  - Identification of periostin as a critical marker of progression/reversal of
      hypertensive nephropathy.
AB  - Progression of chronic kidney disease (CKD) is a major health issue due to
      persistent accumulation of extracellular matrix in the injured kidney. However,
      our current understanding of fibrosis is limited, therapeutic options are
      lacking, and progressive degradation of renal function prevails in CKD patients.
      Uncovering novel therapeutic targets is therefore necessary.We have previously
      demonstrated reversal of renal fibrosis with losartan in experimental
      hypertensive nephropathy. Reversal was achieved provided that the drug was
      administered before late stages of nephropathy, thereby determining a non-return
      point of CKD progression. In the present study, to identify factors critically
      involved in the progression of renal fibrosis, we introduced losartan at the non
      return point in L-NAME treated Sprague Dawley rats. Our results showed either
      reversal or progression of renal disease with losartan, defining 2 groups
      according to the opposite evolution of renal function. We took advantage of these
      experimental conditions to perform a transcriptomic screening to identify novel
      factors potentially implicated in the mechanisms of CKD progression. A secondary
      analysis of selected markers was thereafter performed. Among the targets
      identified, periostin, an extracellular matrix protein, presented a significant
      3.3-fold higher mRNA expression in progression compared to reversal group.
      Furthermore, independent of blood pressure, periostin was strongly correlated
      with plasma creatinine, proteinuria and renal blood flow, hallmarks of
      hypertensive renal disease severity. Periostin staining was predominant in the
      injured regions, both in experimental hypertensive and human nephropathy.These
      results identify periostin as a previously unrecognized marker associated with
      disease progression and regression in hypertensive nephropathy and suggest
      measuring periostin may be a sensitive tool to evaluate severity, progression and
      response to therapy in human kidney disease associated to hypertension.

PMID- 22403622
TI  - Aloe vera induced biomimetic assemblage of nucleobase into nanosized particles.
AB  - AIM: Biomimetic nano-assembly formation offers a convenient and bio friendly
      approach to fabricate complex structures from simple components with sub
      nanometer precision. Recently, biomimetic (employing microorganism/plants)
      synthesis of metal and inorganic materials nano-particles has emerged as a simple
      and viable strategy. In the present study, we have extended biological synthesis
      of nano-particles to organic molecules, namely the anticancer agent 5
      fluorouracil (5-FU), using Aloe vera leaf extract. METHODOLOGY: The 5-FU nano-
      particles synthesized by using Aloe vera leaf extract were characterized by UV,
      FT-IR and fluorescence spectroscopic techniques. The size and shape of the
      synthesized nanoparticles were determined by TEM, while crystalline nature of 5
      FU particles was established by X-ray diffraction study. The cytotoxic effects of
      5-FU nanoparticles were assessed against HT-29 and Caco-2 (human adenocarcinoma
      colorectal) cell lines. RESULTS: Transmission electron microscopy and atomic
      force microscopic techniques confirmed nano-size of the synthesized particles.
      Importantly, the nano-assembled 5-FU retained its anticancer action against
      various cancerous cell lines. CONCLUSION: In the present study, we have explored
      the potential of biomimetic synthesis of nanoparticles employing organic
      molecules with the hope that such developments will be helpful to introduce novel
      nano-particle formulations that will not only be more effective but would also be
      devoid of nano-particle associated putative toxicity constraints.

PMID- 22403623
TI  - Molecular systematics of the deep-sea hydrothermal vent endemic Brachyuran family
      Bythograeidae: a comparison of three Bayesian species tree methods.
AB  - Brachyuran crabs of the family Bythograeidae are endemic to deep-sea hydrothermal
      vents and represent one of the most successful groups of macroinvertebrates that
      have colonized this extreme environment. Occurring worldwide, the family includes
      six genera (Allograea, Austinograea, Bythograea, Cyanagraea, Gandalfus, and
      Segonzacia) and fourteen formally described species. To investigate their
      evolutionary relationships, we conducted Maximum Likelihood and Bayesian
      molecular phylogenetic analyses, based on DNA sequences from fragments of three
      mitochondrial genes (16S rDNA, Cytochrome oxidase I, and Cytochrome b) and three
      nuclear genes (28S rDNA, the sodium-potassium ATPase a-subunit 'NaK', and Histone
      H3A). We employed traditional concatenated (i.e., supermatrix) phylogenetic
      methods, as well as three recently developed Bayesian multilocus methods aimed at
      inferring species trees from potentially discordant gene trees. We found strong
      support for two main clades within Bythograeidae: one comprising the members of
      the genus Bythograea; and the other comprising the remaining genera.
      Relationships within each of these two clades were partially resolved. We compare
      our results with an earlier hypothesis on the phylogenetic relationships among
      bythograeid genera based on morphology. We also discuss the biogeography of the
      family in the light of our results. Our species tree analyses reveal differences
      in how each of the three methods weighs conflicting phylogenetic signal from
      different gene partitions and how limits on the number of outgroup taxa may
      affect the results.

PMID- 22403624
TI  - Adaptive value of phenological traits in stressful environments: predictions
      based on seed production and laboratory natural selection.
AB  - Phenological traits often show variation within and among natural populations of
      annual plants. Nevertheless, the adaptive value of post-anthesis traits is seldom
      tested. In this study, we estimated the adaptive values of pre- and post-anthesis
      traits in two stressful environments (water stress and interspecific
      competition), using the selfing annual species Arabidopsis thaliana. By
      estimating seed production and by performing laboratory natural selection (LNS),
      we assessed the strength and nature (directional, disruptive and stabilizing) of
      selection acting on phenological traits in A. thaliana under the two tested
      stress conditions, each with four intensities. Both the type of stress and its
      intensity affected the strength and nature of selection, as did genetic
      constraints among phenological traits. Under water stress, both experimental
      approaches demonstrated directional selection for a shorter life cycle, although
      bolting time imposes a genetic constraint on the length of the interval between
      bolting and anthesis. Under interspecific competition, results from the two
      experimental approaches showed discrepancies. Estimation of seed production
      predicted directional selection toward early pre-anthesis traits and long post
      anthesis periods. In contrast, the LNS approach suggested neutrality for all
      phenological traits. This study opens questions on adaptation in complex natural
      environment where many selective pressures act simultaneously.

PMID- 22403625
TI  - Spatial scales of bacterial diversity in cold-water coral reef ecosystems.
AB  - BACKGROUND: Cold-water coral reef ecosystems are recognized as biodiversity
      hotspots in the deep sea, but insights into their associated bacterial
      communities are still limited. Deciphering principle patterns of bacterial
      community variation over multiple spatial scales may however prove critical for a
      better understanding of factors contributing to cold-water coral reef stability
      and functioning. METHODOLOGY/PRINCIPAL FINDINGS: Bacterial community structure,
      as determined by Automated Ribosomal Intergenic Spacer Analysis (ARISA), was
      investigated with respect to (i) microbial habitat type and (ii) coral species
      and color, as well as the three spatial components (iii) geomorphologic reef
      zoning, (iv) reef boundary, and (v) reef location. Communities revealed
      fundamental differences between coral-generated (branch surface, mucus) and
      ambient microbial habitats (seawater, sediments). This habitat specificity
      appeared pivotal for determining bacterial community shifts over all other study
      levels investigated. Coral-derived surfaces showed species-specific patterns,
      differing significantly between Lophelia pertusa and Madrepora oculata, but not
      between L. pertusa color types. Within the reef center, no community distinction
      corresponded to geomorphologic reef zoning for both coral-generated and ambient
      microbial habitats. Beyond the reef center, however, bacterial communities varied
      considerably from local to regional scales, with marked shifts toward the reef
      periphery as well as between different in- and offshore reef sites, suggesting
      significant biogeographic imprinting but weak microbe-host specificity.
      CONCLUSIONS/SIGNIFICANCE: This study presents the first multi-scale survey of
      bacterial diversity in cold-water coral reefs, spanning a total of five
      observational levels including three spatial scales. It demonstrates that
      bacterial communities in cold-water coral reefs are structured by multiple
      factors acting at different spatial scales, which has fundamental implications
      for the monitoring of microbial diversity and function in those ecosystems.

PMID- 22403626
TI  - Genetic diversity in new members of the reticulocyte binding protein family in
      Thai Plasmodium vivax isolates.
AB  - BACKGROUND: Plasmodium vivax merozoites specifically invade reticulocytes. Until
      recently, two reticulocyte-binding proteins (Pvrbp1 and Pvrbp2) expressed at the
      apical pole of the P. vivax merozoite were considered to be involved in
      reticulocyte recognition. The genome sequence recently obtained for the Salvador
      I (Sal-I) strain of P. vivax revealed additional genes in this family, and in
      particular Pvrbp2a, Pvrbp2b (Pvrbp2 has been renamed as Pvrbp2c) and two
      pseudogenes Pvrbp2d and Pvrbp3. It had been previously found that Pvrbp2c is
      substantially more polymorphic than Pvrbp1. The primary goal of this study was to
      ascertain the level of polymorphism of these new genes. METHODOLOGY/PRINCIPAL
      FINDINGS: The sequence of the Pvrbp2a, Pvrbp2b, Pvrbp2d and Pvrbp3 genes were
      obtained by amplification/cloning using DNA purified from four isolates collected
      from patients that acquired the infection in the four cardinal regions of
      Thailand (west, north, south and east). An additional seven isolates from western
      Thailand were analyzed for gene copy number variation. There were significant
      polymorphisms exhibited by these genes (compared to the reference Sal-I strain)
      with the ratio of mutations leading to a non-synonymous or synonymous amino acid
      change close to 3?1 for Pvrbp2a and Pvrbp2b. Although the degree of polymorphism
      exhibited by these two genes was higher than that of Pvrbp1, it did not reach the
      exceptional diversity noted for Pvrbp2c. It was interesting to note that
      variations in the copy number of Pvrbp2a and Pvrbp2b occurred in some isolates.
      CONCLUSIONS/SIGNIFICANCE: The evolution of different members of the Pvrbp2 family
      and their relatively high degree of polymorphism suggests that the proteins
      encoded by these genes are important for parasite survival and are under immune
      selection. Our data also shows that there are highly conserved regions in rbp2a
      and rbp2b, which might provide suitable targets for future vaccine development
      against the blood stage of P. vivax.

PMID- 22403627
TI  - Infected dendritic cells facilitate systemic dissemination and transplacental
      passage of the obligate intracellular parasite Neospora caninum in mice.
AB  - The obligate intracellular parasite Neospora caninum disseminates across the
      placenta and the blood-brain barrier, to reach sites where it causes severe
      pathology or establishes chronic persistent infections. The mechanisms used by N.
      caninum to breach restrictive biological barriers remain elusive. To examine the
      cellular basis of these processes, migration of different N. caninum isolates (Nc
      1, Nc-Liverpool, Nc-SweB1 and the Spanish isolates: Nc-Spain 3H, Nc-Spain 4H, Nc
      Spain 6, Nc-Spain 7 and Nc-Spain 9) was studied in an in vitro model based on a
      placental trophoblast-derived BeWo cell line. Here, we describe that infection of
      dendritic cells (DC) by N. caninum tachyzoites potentiated translocation of
      parasites across polarized cellular monolayers. In addition, powered by the
      parasite's own gliding motility, extracellular N. caninum tachyzoites were able
      to transmigrate across cellular monolayers. Altogether, the presented data
      provides evidence of two putative complementary pathways utilized by N. caninum,
      in an isolate-specific fashion, for passage of restrictive cellular barriers.
      Interestingly, adoptive transfer of tachyzoite-infected DC in mice resulted in
      increased parasitic loads in various organs, e.g. the central nervous system,
      compared to infections with free parasites. Inoculation of pregnant mice with
      infected DC resulted in an accentuated vertical transmission to the offspring
      with increased parasitic loads and neonatal mortality. These findings reveal that
      N. caninum exploits the natural cell trafficking pathways in the host to cross
      cellular barriers and disseminate to deep tissues. The findings are indicative of
      conserved dissemination strategies among coccidian apicomplexan parasites.

PMID- 22403628
TI  - Comparison of serum HBsAg quantitation by four immunoassays, and relationships of
      HBsAg level with HBV replication and HBV genotypes.
AB  - BACKGROUND: The decline in hepatitis B virus surface antigen (HBsAg) may be an
      early predictor of the viral efficacy of Hepatitis B virus (HBV) therapy. The
      HBsAg levels obtained by different immunoassays now need comparing and the
      relationships between levels of HBsAg and HBV DNA alongside HBsAg and genotype
      must be evaluated. METHODOLOGY/PRINCIPAL FINDINGS: HBsAg levels were compared
      among 80 patients using the Abbott Architect assay, a commercial immunoassay
      approved for HBsAg detection and quantitation, and three other assays derived
      from immunoassays approved for HBsAg detection (manufactured by Diasorin, Bio-Rad
      and Roche). Good correlation was found between the Abbot vs. Diasorin, Bio-Rad
      and Roche assays with narrow 95% limits of agreement and small mean differences: 
      0.06 to 0.11, -0.09 log(10) IU/mL; -0.57 to 0.64, -0.04 log(10) IU/mL; -0.09 to
      0.45, -0.27 log(10) IU/mL, respectively. These agreements were not affected by
      genotypes A or D. HBsAg was weakly correlated with HBV DNA, whatever the HBsAg
      assay used: Abbott, rho = 0.36 p = 0.001, Diasorin rho = 0.34, p = 0.002; Bio-Rad
      rho = 0.37, p<0.001; or Roche rho = 0.41, p<0.001. This relationship between
      levels of HBsAg and HBV DNA seemed to depend on genotypes. Whereas HBsAg (Abbott
      assay) tended to correlate with HBV DNA for genotype A (rho = 0.44, p = 0.02), no
      such correlation was significant for genotypes D (rho = 0.29, p = 0.15).
      CONCLUSION/SIGNIFICANCE: The quantitation of HBsAg in routine clinical samples is
      comparable between the reference assay and the adapted assays with acceptable
      accuracy limits, low levels of variability and minimum discrepancy. While HBsAg
      quantitation is not affected by HBV genotype, the observed association between
      levels of HBsAg and HBV DNA seems genotype dependent.

PMID- 22403629
TI  - Common variants in the type 2 diabetes KCNQ1 gene are associated with impairments
      in insulin secretion during hyperglycaemic glucose clamp.
AB  - BACKGROUND: Genome-wide association studies in Japanese populations recently
      identified common variants in the KCNQ1 gene to be associated with type 2
      diabetes. We examined the association of these variants within KCNQ1 with type 2
      diabetes in a Dutch population, investigated their effects on insulin secretion
      and metabolic traits and on the risk of developing complications in type 2
      diabetes patients. METHODOLOGY: The KCNQ1 variants rs151290, rs2237892, and
      rs2237895 were genotyped in a total of 4620 type 2 diabetes patients and 5285
      healthy controls from the Netherlands. Data on macrovascular complications,
      nephropathy and retinopathy were available in a subset of diabetic patients.
      Association between genotype and insulin secretion/action was assessed in the
      additional sample of 335 individuals who underwent a hyperglycaemic clamp.
      PRINCIPAL FINDINGS: We found that all the genotyped KCNQ1 variants were
      significantly associated with type 2 diabetes in our Dutch population, and the
      association of rs151290 was the strongest (OR 1.20, 95% CI 1.07-1.35, p = 0.002).
      The risk C-allele of rs151290 was nominally associated with reduced first-phase
      glucose-stimulated insulin secretion, while the non-risk T-allele of rs2237892
      was significantly correlated with increased second-phase glucose-stimulated
      insulin secretion (p = 0.025 and 0.0016, respectively). In addition, the risk C
      allele of rs2237892 was associated with higher LDL and total cholesterol levels
      (p = 0.015 and 0.003, respectively). We found no evidence for an association of
      KCNQ1 with diabetic complications. CONCLUSIONS: Common variants in the KCNQ1 gene
      are associated with type 2 diabetes in a Dutch population, which can be explained
      at least in part by an effect on insulin secretion. Furthermore, our data suggest
      that KCNQ1 is also associated with lipid metabolism.

PMID- 22403630
TI  - Isolation of a 97-kb minimal essential MHC B locus from a new reverse-4D BAC
      library of the golden pheasant.
AB  - The bacterial artificial chromosome (BAC) system is widely used in isolation of
      large genomic fragments of interest. Construction of a routine BAC library
      requires several months for picking clones and arraying BACs into superpools in
      order to employ 4D-PCR to screen positive BACs, which might be time-consuming and
      laborious. The major histocompatibility complex (MHC) is a cluster of genes
      involved in the vertebrate immune system, and the classical avian MHC-B locus is
      a minimal essential one, occupying a 100-kb genomic region. In this study, we
      constructed a more effective reverse-4D BAC library for the golden pheasant,
      which first creates sub-libraries and then only picks clones of positive sub
      libraries, and identified several MHC clones within thirty days. The full
      sequencing of a 97-kb reverse-4D BAC demonstrated that the golden pheasant MHC-B
      locus contained 20 genes and showed good synteny with that of the chicken. The
      notable differences between these two species were the numbers of class II B loci
      and NK genes and the inversions of the TAPBP gene and the TAP1-TAP2 region.
      Furthermore, the inverse TAP2-TAP1 was unique in the golden pheasant in
      comparison with that of chicken, turkey, and quail. The newly defined genomic
      structure of the golden pheasant MHC will give an insight into the evolutionary
      history of the avian MHC.

PMID- 22403631
TI  - Epidermal growth factor gene polymorphism and risk of hepatocellular carcinoma: a
      meta-analysis.
AB  - BACKGROUND: Hepatocarcinogenesis is a complex process that may be influenced by
      many factors, including polymorphism in the epidermal growth factor (EGF) gene.
      Previous work suggests an association between the EGF 61*A/G polymorphism
      (rs4444903) and susceptibility to hepatocellular carcinoma (HCC), but the results
      have been inconsistent. Therefore, we performed a meta-analysis of several
      studies covering a large population to address this controversy. METHODS: PubMed,
      EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure
      databases were systematically searched to identify relevant studies. Data were
      abstracted independently by two reviewers. A meta-analysis was performed to
      examine the association between EGF 61*A/G polymorphism and susceptibility to
      HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.
      RESULTS: Eight studies were chosen in this meta-analysis, involving 1,304 HCC
      cases (1135 Chinese, 44 Caucasian and 125 mixed) and 2,613 controls (1638
      Chinese, 77 Caucasian and 898 mixed). The EGF 61*G allele was significantly
      associated with increased risk of HCC based on allelic contrast (OR = 1.29, 95%
      CI = 1.16-1.44, p<0.001), homozygote comparison (OR = 1.79, 95% CI = 1.39-2.29,
      p<0.001) and a recessive genetic model (OR = 1.34, 95% CI = 1.16-1.54, p<0.001),
      while patients carrying the EGF 61*A/A genotype had significantly lower risk of
      HCC than those with the G/A or G/G genotype (A/A vs. G/A+G/G, OR = 0.66, 95% CI =
      0.53-0.83, p<0.001). CONCLUSION: The 61*G polymorphism in EGF is a risk factor
      for hepatocarcinogenesis while the EGF 61*A allele is a protective factor.
      Further large and well-designed studies are needed to confirm this conclusion.

PMID- 22403632
TI  - Trans fat consumption and aggression.
AB  - BACKGROUND: Dietary trans fatty acids (dTFA) are primarily synthetic compounds
      that have been introduced only recently; little is known about their behavioral
      effects. dTFA inhibit production of omega-3 fatty acids, which experimentally
      have been shown to reduce aggression. Potential behavioral effects of dTFA merit
      investigation. We sought to determine whether dTFA are associated with
      aggression/irritability. METHODOLGY/PRINICPAL FINDINGS: We capitalized on
      baseline dietary and behavioral assessments in an existing clinical trial to
      analyze the relationship of dTFA to aggression. Of 1,018 broadly sampled baseline
      subjects, the 945 adult men and women who brought a completed dietary survey to
      their baseline visit are the target of this analysis. Subjects (seen 1999-2004)
      were not on lipid medications, and were without LDL-cholesterol extremes,
      diabetes, HIV, cancer or heart disease. Outcomes assessed adverse behaviors with
      impact on others: Overt Aggression Scale Modified-aggression subscale (primary
      behavioral endpoint); Life History of Aggression; Conflict Tactics Scale; and
      self-rated impatience and irritability. The association of dTFA to aggression was
      analyzed via regression and ordinal logit, unadjusted and adjusted for potential
      confounders (sex, age, education, alcohol, and smoking). Additional analyses
      stratified on sex, age, and ethnicity, and examined the prospective association.
      Greater dTFA were strongly significantly associated with greater aggression, with
      dTFA more consistently predictive than other assessed aggression predictors. The
      relationship was upheld with adjustment for confounders, was preserved across
      sex, age, and ethnicity strata, and held cross-sectionally and prospectively.
      CONCLUSIONS/SIGNIFICANCE: This study provides the first evidence linking dTFA
      with behavioral irritability and aggression. While confounding is always a
      concern in observational studies, factors including strength and consistency of
      association, biological gradient, temporality, and biological plausibility add
      weight to the prospect of a causal connection. Our results may have relevance to
      public policy determinations regarding dietary trans fats. Clinicaltrials.gov #
      NCT00330980.

PMID- 22403633
TI  - Effect of size and heterogeneity of samples on biomarker discovery: synthetic and
      real data assessment.
AB  - MOTIVATION: The identification of robust lists of molecular biomarkers related to
      a disease is a fundamental step for early diagnosis and treatment. However,
      methodologies for the discovery of biomarkers using microarray data often provide
      results with limited overlap. These differences are imputable to 1) dataset size
      (few subjects with respect to the number of features); 2) heterogeneity of the
      disease; 3) heterogeneity of experimental protocols and computational pipelines
      employed in the analysis. In this paper, we focus on the first two issues and
      assess, both on simulated (through an in silico regulation network model) and
      real clinical datasets, the consistency of candidate biomarkers provided by a
      number of different methods. METHODS: We extensively simulated the effect of
      heterogeneity characteristic of complex diseases on different sets of microarray
      data. Heterogeneity was reproduced by simulating both intrinsic variability of
      the population and the alteration of regulatory mechanisms. Population
      variability was simulated by modeling evolution of a pool of subjects; then, a
      subset of them underwent alterations in regulatory mechanisms so as to mimic the
      disease state. RESULTS: The simulated data allowed us to outline advantages and
      drawbacks of different methods across multiple studies and varying number of
      samples and to evaluate precision of feature selection on a benchmark with known
      biomarkers. Although comparable classification accuracy was reached by different
      methods, the use of external cross-validation loops is helpful in finding
      features with a higher degree of precision and stability. Application to real
      data confirmed these results.

PMID- 22403634
TI  - Evaluating temporal factors in combined interventions of workforce shift and
      school closure for mitigating the spread of influenza.
AB  - BACKGROUND: It is believed that combined interventions may be more effective than
      individual interventions in mitigating epidemic. However there is a lack of
      quantitative studies on performance of the combination of individual
      interventions under different temporal settings. METHODOLOGY/PRINCIPAL FINDINGS:
      To better understand the problem, we develop an individual-based simulation model
      running on top of contact networks based on real-life contact data in Singapore.
      We model and evaluate the spread of influenza epidemic with intervention
      strategies of workforce shift and its combination with school closure, and
      examine the impacts of temporal factors, namely the trigger threshold and the
      duration of an intervention. By comparing simulation results for intervention
      scenarios with different temporal factors, we find that combined interventions do
      not always outperform individual interventions and are more effective only when
      the duration is longer than 6 weeks or school closure is triggered at the 5%
      threshold; combined interventions may be more effective if school closure starts
      first when the duration is less than 4 weeks or workforce shift starts first when
      the duration is longer than 4 weeks. CONCLUSIONS/SIGNIFICANCE: We therefore
      conclude that identifying the appropriate timing configuration is crucial for
      achieving optimal or near optimal performance in mitigating the spread of
      influenza epidemic. The results of this study are useful to policy makers in
      deliberating and planning individual and combined interventions.

PMID- 22403635
TI  - Genetic diversity and population parameters of sea otters, Enhydra lutris, before
      fur trade extirpation from 1741-1911.
AB  - All existing sea otter, Enhydra lutris, populations have suffered at least one
      historic population bottleneck stemming from the fur trade extirpations of the
      eighteenth and nineteenth centuries. We examined genetic variation, gene flow,
      and population structure at five microsatellite loci in samples from five pre-fur
      trade populations throughout the sea otter's historical range: California,
      Oregon, Washington, Alaska, and Russia. We then compared those values to genetic
      diversity and population structure found within five modern sea otter populations
      throughout their current range: California, Prince William Sound, Amchitka
      Island, Southeast Alaska and Washington. We found twice the genetic diversity in
      the pre-fur trade populations when compared to modern sea otters, a level of
      diversity that was similar to levels that are found in other mammal populations
      that have not experienced population bottlenecks. Even with the significant loss
      in genetic diversity modern sea otters have retained historical structure. There
      was greater gene flow before extirpation than that found among modern sea otter
      populations but the difference was not statistically significant. The most
      dramatic effect of pre fur trade population extirpation was the loss of genetic
      diversity. For long term conservation of these populations increasing gene flow
      and the maintenance of remnant genetic diversity should be encouraged.

PMID- 22403636
TI  - Single cycle structure-based humanization of an anti-nerve growth factor
      therapeutic antibody.
AB  - Most forms of chronic pain are inadequately treated by present therapeutic
      options. Compelling evidence has accumulated, demonstrating that Nerve Growth
      Factor (NGF) is a key modulator of inflammatory and nociceptive responses, and is
      a promising target for the treatment of human pathologies linked to chronic and
      inflammatory pain. There is therefore a growing interest in the development of
      therapeutic molecules antagonising the NGF pathway and its nociceptor
      sensitization actions, among which function-blocking anti-NGF antibodies are
      particularly relevant candidates.In this respect, the rat anti-NGF alphaD11
      monoclonal antibody (mAb) is a potent antagonist, able to effectively antagonize
      rodent and human NGF in a variety of in vitro and in vivo systems. Here we show
      that mAb alphaD11 displays a significant analgesic effect in two different models
      of persistent pain in mice, with a remarkable long-lasting activity. In order to
      advance alphaD11 mAb towards its clinical application in man, anti-NGF alphaD11
      mAb was humanized by applying a novel single cycle strategy based on the a priori
      experimental determination of the crystal and molecular structure of the parental
      Fragment antigen-binding (Fab). The humanized antibody (hum-alphaD11) was tested
      in vitro and in vivo, showing that the binding mode and the NGF neutralizing
      biological activities of the parental antibody are fully preserved, with even a
      significant affinity improvement. The results firmly establish hum-alphaD11 as a
      lead candidate for clinical applications in a therapeutic area with a severe
      unmet medical need. More generally, the single-cycle structure-based humanization
      method represents a considerable improvement over the standard humanization
      methods, which are intrinsically empirical and require several refinement cycles.

PMID- 22403637
TI  - Identifying low pH active and lactate-utilizing taxa within oral microbiome
      communities from healthy children using stable isotope probing techniques.
AB  - BACKGROUND: Many human microbial infectious diseases including dental caries are
      polymicrobial in nature. How these complex multi-species communities evolve from
      a healthy to a diseased state is not well understood. Although many health- or
      disease-associated oral bacteria have been characterized in vitro, their
      physiology within the complex oral microbiome is difficult to determine with
      current approaches. In addition, about half of these species remain uncultivated
      to date with little known besides their 16S rRNA sequence. Lacking culture-based
      physiological analyses, the functional roles of uncultivated species will remain
      enigmatic despite their apparent disease correlation. To start addressing these
      knowledge gaps, we applied a combination of Magnetic Resonance Spectroscopy (MRS)
      with RNA and DNA based Stable Isotope Probing (SIP) to oral plaque communities
      from healthy children for in vitro temporal monitoring of metabolites and
      identification of metabolically active and inactive bacterial species.
      METHODOLOGY/PRINCIPAL FINDINGS: Supragingival plaque samples from caries-free
      children incubated with (13)C-substrates under imposed healthy (buffered, pH 7)
      and diseased states (pH 5.5 and pH 4.5) produced lactate as the dominant organic
      acid from glucose metabolism. Rapid lactate utilization upon glucose depletion
      was observed under pH 7 conditions. SIP analyses revealed a number of genera
      containing cultured and uncultivated taxa with metabolic capabilities at pH 5.5.
      The diversity of active species decreased significantly at pH 4.5 and was
      dominated by Lactobacillus and Propionibacterium species, both of which have been
      previously found within carious lesions from children. CONCLUSIONS/SIGNIFICANCE:
      Our approach allowed for identification of species that metabolize carbohydrates
      under different pH conditions and supports the importance of Lactobacilli and
      Propionibacterium in the development of childhood caries. Identification of
      species within healthy subjects that are active at low pH can lead to a better
      understanding of oral caries onset and generate appropriate targets for
      preventative measures in the early stages.

PMID- 22403638
TI  - Development of a humanized HLA-A2.1/DP4 transgenic mouse model and the use of
      this model to map HLA-DP4-restricted epitopes of HBV envelope protein.
AB  - A new homozygous humanized transgenic mouse strain, HLA-A2.1(+/+)HLA-DP4(+/+)
      hCD4(+/+)mCD4(-/-)IAbeta(-/-)beta2m(-/-) (HLA-A2/DP4), was obtained by crossing
      the previously characterized HLA-A2(+/+)beta2m(-/-) (A2) mouse and our previously
      created HLA-DP4(+/+) hCD4(+/+)mCD4(-/-)IAbeta(-/-) (DP4) mouse. We confirmed that
      the transgenes (HLA-A2, HLA-DP4, hCD4) inherited from the parental A2 and DP4
      mice are functional in the HLA-A2/DP4 mice. After immunizing HLA-A2/DP4 mice with
      a hepatitis B DNA vaccine, hepatitis B virus-specific antibodies, HLA-A2
      restricted and HLA-DP4-restricted responses were observed to be similar to those
      in naturally infected humans. Therefore, the present study demonstrated that HLA
      A2/DP4 transgenic mice can faithfully mimic human cellular responses.
      Furthermore, we reported four new HLA-DP4-restricted epitopes derived from HBsAg
      that were identified in both vaccinated HLA-A2/DP4 mice and HLA-DP4-positive
      human individuals. The HLA-A2/DP4 mouse model is a promising preclinical animal
      model carrying alleles present to more than a quarter of the human population.
      This model should facilitate the identification of novel HLA-A2- and HLA-DP4
      restricted epitopes and vaccine development as well as the characterization of
      HLA-DP4-restricted responses against infection in humans.

PMID- 22403639
TI  - Male microchimerism at high levels in peripheral blood mononuclear cells from
      women with end stage renal disease before kidney transplantation.
AB  - Patients with end stage renal diseases (ESRD) are generally tested for donor
      chimerism after kidney transplantation for tolerance mechanism purposes. But, to
      our knowledge, no data are available on natural and/or iatrogenic microchimerism
      (Mc), deriving from pregnancy and/or blood transfusion, acquired prior to
      transplantation. In this context, we tested the prevalence of male Mc using a
      real time PCR assay for DYS14, a Y-chromosome specific sequence, in peripheral
      blood mononuclear cells (PBMC) from 55 women with ESRD, prior to their first
      kidney transplantation, and compared them with results from 82 healthy women.
      Male Mc was also quantified in 5 native kidney biopsies obtained two to four
      years prior to blood testing and in PBMC from 8 women collected after female
      kidney transplantation, several years after the initial blood testing. Women with
      ESRD showed statistically higher frequencies (62%) and quantities (98 genome
      equivalent cells per million of host cells, gEq/M) of male Mc in their PBMC than
      healthy women (16% and 0.3 gEq/M, p<0.00001 and p = 0.0005 respectively). Male Mc
      was increased in women with ESRD whether they had or not a history of male
      pregnancy and/or of blood transfusion. Three out of five renal biopsies obtained
      a few years prior to the blood test also contained Mc, but no correlation could
      be established between earlier Mc in a kidney and later presence in PBMC.
      Finally, several years after female kidney transplantation, male Mc was totally
      cleared from PBMC in all women tested but one. This intriguing and striking
      initial result of natural and iatrogenic male Mc persistence in peripheral blood
      from women with ESRD raises several hypotheses for the possible role of these
      cells in renal diseases. Further studies are needed to elucidate mechanisms of
      recruitment and persistence of Mc in women with ESRD.

PMID- 22403640
TI  - Diphenyl urea derivatives as inhibitors of transketolase: a structure-based
      virtual screening.
AB  - Transketolase is an enzyme involved in a critical step of the non-oxidative
      branch of the pentose phosphate pathway whose inhibition could lead to new
      anticancer drugs. Here, we report new human transketolase inhibitors, based on
      the phenyl urea scaffold, found by applying structure-based virtual screening.
      These inhibitors are designed to cover a hot spot in the dimerization interface
      of the homodimer of the enzyme, providing for the first time compounds with a
      suggested novel binding mode not based on mimicking the thiamine pyrophosphate
      cofactor.

PMID- 22403641
TI  - The interactive effects of ammonia and microcystin on life-history traits of the
      cladoceran Daphnia magna: synergistic or antagonistic?
AB  - The occurrence of Microcystis blooms is a worldwide concern that has caused
      numerous adverse effects on water quality and lake ecology. Elevated ammonia and
      microcystin concentrations co-occur during the degradation of Microcystis blooms
      and are toxic to aquatic organisms; we studied the relative and combined effects
      of these on the life history of the model organism Daphnia magna. Ammonia and
      microcystin-LR treatments were: 0, 0.366, 0.581 mg L(-1) and 0, 10, 30, 100 ug L(
      1), respectively. Experiments followed a fully factorial design. Incubations were
      14 d and recorded the following life-history traits: number of moults, time to
      first batch of eggs, time to first clutch, size at first batch of eggs, size at
      first clutch, number of clutches per female, number of offspring per clutch, and
      total offspring per female. Both ammonia and microcystin were detrimental to most
      life-history traits. Interactive effects of the toxins occurred for five traits:
      the time to first batch of eggs appearing in the brood pouch, time to first
      clutch, size at first clutch, number of clutches, and total offspring per female.
      The interactive effects of ammonia and microcystin appeared to be synergistic on
      some parameters (e.g., time to first eggs) and antagonistic on others (e.g.,
      total offspring per female). In conclusion, the released toxins during the
      degradation of Microcystis blooms would result, according to our data, in
      substantially negative effect on D. magna.

PMID- 22403642
TI  - Experimental quantification of long distance dispersal potential of aquatic
      snails in the gut of migratory birds.
AB  - Many plant seeds and invertebrates can survive passage through the digestive
      system of birds, which may lead to long distance dispersal (endozoochory) in case
      of prolonged retention by moving vectors. Endozoochorous dispersal by waterbirds
      has nowadays been documented for many aquatic plant seeds, algae and dormant life
      stages of aquatic invertebrates. Anecdotal information indicates that
      endozoochory is also possible for fully functional, active aquatic organisms, a
      phenomenon that we here address experimentally using aquatic snails. We fed four
      species of aquatic snails to mallards (Anas platyrhynchos), and monitored snail
      retrieval and survival over time. One of the snail species tested was found to
      survive passage through the digestive tract of mallards as fully functional
      adults. Hydrobia (Peringia) ulvae survived up to five hours in the digestive
      tract. This suggests a maximum potential transport distance of up to 300 km may
      be possible if these snails are taken by flying birds, although the actual
      dispersal distance greatly depends on additional factors such as the behavior of
      the vectors. We put forward that more organisms that acquired traits for survival
      in stochastic environments such as wetlands, but not specifically adapted for
      endozoochory, may be sufficiently equipped to successfully pass a bird's
      digestive system. This may be explained by a digestive trade-off in birds, which
      maximize their net energy intake rate rather than digestive efficiency, since
      higher efficiency comes with the cost of prolonged retention times and hence
      reduces food intake. The resulting lower digestive efficiency allows species like
      aquatic snails, and potentially other fully functional organisms without obvious
      dispersal adaptations, to be transported internally. Adopting this view,
      endozoochorous dispersal may be more common than up to now thought.

PMID- 22403643
TI  - WNT5 interacts with the Ryk receptors doughnut and derailed to mediate muscle
      attachment site selection in Drosophila melanogaster.
AB  - In recent years a number of the genes that regulate muscle formation and
      maintenance in higher organisms have been identified. Studies employing
      invertebrate and vertebrate model organisms have revealed that many of the genes
      required for early mesoderm specification are highly conserved throughout
      evolution. Less is known about the molecules that mediate the steps subsequent to
      myogenesis, e. g. myotube guidance and attachment to tendon cells. We use the
      stereotypic pattern of the Drosophila embryonic body wall musculature in genetic
      approaches to identify novel factors required for muscle attachment site
      selection. Here, we show that Wnt5 is needed in this process. The lateral
      transverse muscles frequently overshoot their target attachment sites and stably
      attach at novel epidermal sites in Wnt5 mutant embryos. Restoration of WNT5
      expression in either the muscle or the tendon cell rescues the mutant phenotype.
      Surprisingly, the novel attachment sites in Wnt5 mutants frequently do not
      express the Stripe (SR) protein which has been shown to be required for terminal
      tendon cell differentiation. A muscle bypass phenotype was previously reported
      for embryos lacking the WNT5 receptor Derailed (DRL). drl and Wnt5 mutant embryos
      also exhibit axon path finding errors. DRL belongs to the conserved Ryk receptor
      tyrosine kinase family which includes two other Drosophila orthologs, the
      Doughnut on 2 (DNT) and Derailed-2 (DRL-2) proteins. We generated a mutant allele
      of dnt and find that dnt, but not Drl-2, mutant embryos also show a muscle bypass
      phenotype. Genetic interaction experiments indicate that drl and dnt act
      together, likely as WNT5 receptors, to control muscle attachment site selection.
      These results extend previous findings that at least some of the molecular
      pathways that guide axons towards their targets are also employed for guidance of
      muscle fibers to their appropriate attachment sites.

PMID- 22403644
TI  - Cd2+ Toxicity to a green alga Chlamydomonas reinhardtii as influenced by its
      adsorption on TiO2 engineered nanoparticles.
AB  - In the present study, Cd(2+) adsorption on polyacrylate-coated TiO(2) engineered
      nanoparticles (TiO(2)-ENs) and its effect on the bioavailability as well as
      toxicity of Cd(2+) to a green alga Chlamydomonas reinhardtii were investigated.
      TiO(2)-ENs could be well dispersed in the experimental medium and their pH(pzc)
      is approximately 2. There was a quick adsorption of Cd(2+) on TiO(2)-ENs and a
      steady state was reached within 30 min. A pseudo-first order kinetics was found
      for the time-related changes in the amount of Cd(2+) complexed with TiO(2)-ENs.
      At equilibrium, Cd(2+) adsorption followed the Langmuir isotherm with the maximum
      binding capacity 31.9, 177.1, and 242.2 mg/g when the TiO(2)-EN concentration was
      1, 10, and 100 mg/l, respectively. On the other hand, Cd(2+) toxicity was
      alleviated in the presence of TiO(2)-ENs. Algal growth was less suppressed in
      treatments with comparable total Cd(2+) concentration but more TiO(2)-ENs.
      However, such toxicity difference disappeared and all the data points could be
      fitted to a single Logistic dose-response curve when cell growth inhibition was
      plotted against the free Cd(2+) concentration. No detectable amount of TiO(2)-ENs
      was found to be associated with the algal cells. Therefore, TiO(2)-ENs could
      reduce the free Cd(2+) concentration in the toxicity media, which further lowered
      its bioavailability and toxicity to C. reinhardtii.

PMID- 22403645
TI  - Listeriolysin o is strongly immunogenic independently of its cytotoxic activity.
AB  - The presentation of microbial protein antigens by Major Histocompatibility
      Complex (MHC) molecules is essential for the development of acquired immunity to
      infections. However, most biochemical studies of antigen processing and
      presentation deal with a few relatively inert non-microbial model antigens. The
      bacterial pore-forming toxin listeriolysin O (LLO) is paradoxical in that it is
      cytotoxic at nanomolar concentrations as well as being the source of dominant CD4
      and CD8 T cell epitopes following infection with Listeria monocytogenes. Here, we
      examined the relationship of LLO toxicity to its antigenicity and immunogenicity.
      LLO offered to antigen presenting cells (APC) as a soluble protein, was presented
      to CD4 T cells at picomolar to femtomolar concentrations- doses 3000-7000-fold
      lower than free peptide. This presentation required a dose of LLO below the
      cytotoxic level. Mutations of two key tryptophan residues reduced LLO toxicity by
      10-100-fold but had no effect on its presentation to CD4 T cells. Thus there was
      a clear dissociation between the cytotoxic properties of LLO and its very high
      antigenicity. Presentation of LLO to CD8 T cells was not as robust as that seen
      in CD4 T cells, but still occurred in the nanomolar range. APC rapidly bound and
      internalized LLO, then disrupted endosomal compartments within 4 hours of
      treatment, allowing endosomal contents to access the cytosol. LLO was also
      immunogenic after in vivo administration into mice. Our results demonstrate the
      strength of LLO as an immunogen to both CD4 and CD8 T cells.

PMID- 22403647
TI  - The optimal exponent base for emPAI is 6.5.
AB  - Exponentially Modified Protein Abundance Index (emPAI) is an established method
      of estimating protein abundances from peptide counts in a single LC-MS/MS
      experiment. EmPAI is defined as 10(PAI) minus one, where PAI (Protein Abundance
      Index) denotes the ratio of observed to observable peptides. EmPAI was first
      proposed by Ishihama et al [1] who found that PAI is approximately proportional
      to the logarithm of absolute protein concentration. I define emPAI65 = 6.5(PAI)-1
      and show that it performs significantly better than emPAI, while it is equally
      easy to compute. The higher accuracy of emPAI65 is demonstrated by analyzing
      three data sets, including the one used in the original study [1]. I conclude
      that emPAI65 ought to be used instead of the original emPAI for protein
      quantitation.

PMID- 22403646
TI  - A genome-wide association study identifies rs2000999 as a strong genetic
      determinant of circulating haptoglobin levels.
AB  - Haptoglobin is an acute phase inflammatory marker. Its main function is to bind
      hemoglobin released from erythrocytes to aid its elimination, and thereby
      haptoglobin prevents the generation of reactive oxygen species in the blood.
      Haptoglobin levels have been repeatedly associated with a variety of inflammation
      linked infectious and non-infectious diseases, including malaria, tuberculosis,
      human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and
      acute myocardial infarction. However, a comprehensive genetic assessment of the
      inter-individual variability of circulating haptoglobin levels has not been
      conducted so far.We used a genome-wide association study initially conducted in
      631 French children followed by a replication in three additional European sample
      sets and we identified a common single nucleotide polymorphism (SNP), rs2000999
      located in the Haptoglobin gene (HP) as a strong genetic predictor of circulating
      Haptoglobin levels (P(overall) = 8.1 * 10(-59)), explaining 45.4% of its genetic
      variability (11.8% of Hp global variance). The functional relevance of rs2000999
      was further demonstrated by its specific association with HP mRNA levels (beta =
      0.23 +/- 0.08, P = 0.007). Finally, SNP rs2000999 was associated with decreased
      total and low-density lipoprotein cholesterol in 8,789 European children (P(total
      cholesterol) = 0.002 and P(LDL) = 0.0008).Given the central position of
      haptoglobin in many inflammation-related metabolic pathways, the relevance of
      rs2000999 genotyping when evaluating haptoglobin concentration should be further
      investigated in order to improve its diagnostic/therapeutic and/or prevention
      impact.

PMID- 22403648
TI  - The bone-forming effects of HIF-1alpha-transduced BMSCs promote osseointegration
      with dental implant in canine mandible.
AB  - The presence of insufficient bone volume remains a major clinical problem for
      dental implant placement to restore the oral function. Gene-transduced stem cells
      provide a promising approach for inducing bone regeneration and enhancing
      osseointegration in dental implants with tissue engineering technology. Our
      previous studies have demonstrated that the hypoxia-inducible factor-1alpha (HIF
      1alpha) promotes osteogenesis in rat bone mesenchymal stem cells (BMSCs). In this
      study, the function of HIF-1alpha was validated for the first time in a
      preclinical large animal canine model in term of its ability to promote new bone
      formation in defects around implants as well as the osseointegration between
      tissue-engineered bone and dental implants. A lentiviral vector was constructed
      with the constitutively active form of HIF-1alpha (cHIF). The ectopic bone
      formation was evaluated in nude mice. The therapeutic potential of HIF-1alpha
      overexpressing canine BMSCs in bone repair was evaluated in mesi-implant defects
      of immediate post-extraction implants in the canine mandible. HIF-1alpha mediated
      canine BMSCs significantly promoted new bone formation both subcutaneously and in
      mesi-implant defects, including increased bone volume, bone mineral density,
      trabecular thickness, and trabecular bone volume fraction. Furthermore,
      osseointegration was significantly enhanced by HIF-1alpha-overexpressing canine
      BMSCs. This study provides an important experimental evidence in a preclinical
      large animal model concerning to the potential applications of HIF-1alpha in
      promoting new bone formation as well as the osseointegration of immediate
      implantation for oral function restoration.

PMID- 22403650
TI  - Do behavioral foraging responses of prey to predators function similarly in
      restored and pristine foodwebs?
AB  - Efforts to restore top predators in human-altered systems raise the question of
      whether rebounds in predator populations are sufficient to restore pristine
      foodweb dynamics. Ocean ecosystems provide an ideal system to test this question.
      Removal of fishing in marine reserves often reverses declines in predator
      densities and size. However, whether this leads to restoration of key functional
      characteristics of foodwebs, especially prey foraging behavior, is unclear. The
      question of whether restored and pristine foodwebs function similarly is
      nonetheless critically important for management and restoration efforts. We
      explored this question in light of one important determinant of ecosystem
      function and structure--herbivorous prey foraging behavior. We compared these
      responses for two functionally distinct herbivorous prey fishes (the damselfish
      Plectroglyphidodon dickii and the parrotfish Chlorurus sordidus) within pairs of
      coral reefs in pristine and restored ecosystems in two regions of these species'
      biogeographic ranges, allowing us to quantify the magnitude and temporal scale of
      this key ecosystem variable's recovery. We demonstrate that restoration of top
      predator abundances also restored prey foraging excursion behaviors to a
      condition closely resembling those of a pristine ecosystem. Increased
      understanding of behavioral aspects of ecosystem change will greatly improve our
      ability to predict the cascading consequences of conservation tools aimed at
      ecological restoration, such as marine reserves.

PMID- 22403649
TI  - Amino acid residues contributing to function of the heteromeric insect olfactory
      receptor complex.
AB  - Olfactory receptors (Ors) convert chemical signals--the binding of odors and
      pheromones--to electrical signals through the depolarization of olfactory sensory
      neurons. Vertebrates Ors are G-protein-coupled receptors, stimulated by odors to
      produce intracellular second messengers that gate ion channels. Insect Ors are a
      heteromultimeric complex of unknown stoichiometry of two seven transmembrane
      domain proteins with no sequence similarity to and the opposite membrane topology
      of G-protein-coupled receptors. The functional insect Or comprises an odor- or
      pheromone-specific Or subunit and the Orco co-receptor, which is highly conserved
      in all insect species. The insect Or-Orco complex has been proposed to function
      as a novel type of ligand-gated nonselective cation channel possibly modulated by
      G-proteins. However, the Or-Orco proteins lack homology to any known family of
      ion channel and lack known functional domains. Therefore, the mechanisms by which
      odors activate the Or-Orco complex and how ions permeate this complex remain
      unknown. To begin to address the relationship between Or-Orco structure and
      function, we performed site-directed mutagenesis of all 83 conserved Glu, Asp, or
      Tyr residues in the silkmoth BmOr-1-Orco pheromone receptor complex and measured
      functional properties of mutant channels expressed in Xenopus oocytes. 13 of 83
      mutations in BmOr-1 and BmOrco altered the reversal potential and rectification
      index of the BmOr-1-Orco complex. Three of the 13 amino acids (D299 and E356 in
      BmOr-1 and Y464 in BmOrco) altered both current-voltage relationships and K(+)
      selectivity. We introduced the homologous Orco Y464 residue into Drosophila Orco
      in vivo, and observed variable effects on spontaneous and evoked action
      potentials in olfactory neurons that depended on the particular Or-Orco complex
      examined. Our results provide evidence that a subset of conserved Glu, Asp and
      Tyr residues in both subunits are essential for channel activity of the
      heteromeric insect Or-Orco complex.

PMID- 22403651
TI  - Sex differences in the association between serum levels of testosterone and
      frailty in an elderly population: the Toledo Study for Healthy Aging.
AB  - BACKGROUND: Age-associated decline in testosterone levels represent one of the
      potential mechanisms involved in the development of frailty. Although this
      association has been widely reported in older men, very few data are available in
      women. We studied the association between testosterone and frailty in women and
      assessed sex differences in this relationship. METHODS: We used cross-sectional
      data from the Toledo Study for Healthy Aging, a population-based cohort study of
      Spanish elderly. Frailty was defined according to Fried's approach. Multivariate
      odds-ratios (OR) and 95% confidence intervals (CI) associated with total (TT) and
      free testosterone (FT) levels were estimated using polytomous logistic
      regression. RESULTS: In women, there was a U-shaped relationship between FT
      levels and frailty (p for FT(2) = 0.03). In addition, very low levels of FT were
      observed in women with >= 4 frailty criteria (age-adjusted geometric means = 0.13
      versus 0.37 in subjects with <4 components, p = 0.010). The association of FT
      with frailty appeared confined to obese women (p-value for interaction = 0.05).In
      men, the risk of frailty levels linearly decreased with testosterone (adjusted OR
      for frailty = 2.9 (95%CI, 1.6-5.1) and 1.6 (95%CI, 1.0-2.5), for 1 SD decrease in
      TT and FT, respectively). TT and FT showed association with most of frailty
      criteria. No interaction was found with BMI. CONCLUSION: There is a relationship
      between circulating levels of FT and frailty in older women. This relation seems
      to be modulated by BMI. The relevance and the nature of the association of FT
      levels and frailty are sex-specific, suggesting that different biological
      mechanisms may be involved.

PMID- 22403652
TI  - Your unconscious knows your name.
AB  - One's own name constitutes a unique part of conscious awareness - but does this
      also hold true for unconscious processing? The present study shows that the own
      name has the power to bias a person's actions unconsciously even in conditions
      that render any other name ineffective. Participants judged whether a letter
      string on the screen was a name or a non-word while this target stimulus was
      preceded by a masked prime stimulus. Crucially, the participant's own name was
      among these prime stimuli and facilitated reactions to following name targets
      whereas the name of another, yoked participant did not. Signal detection results
      confirmed that participants were not aware of any of the prime stimuli, including
      their own name. These results extend traditional findings on "breakthrough"
      phenomena of personally relevant stimuli to the domain of unconscious processing.
      Thus, the brain seems to possess adroit mechanisms to identify and process such
      stimuli even in the absence of conscious awareness.

PMID- 22403653
TI  - A battle lost? Report on two centuries of invasion and management of Lantana
      camara L. in Australia, India and South Africa.
AB  - Recent discussion on invasive species has invigorated the debate on strategies to
      manage these species. Lantana camara L., a shrub native to the American tropics,
      has become one of the worst weeds in recorded history. In Australia, India and
      South Africa, Lantana has become very widespread occupying millions of hectares
      of land. Here, we examine historical records to reconstruct invasion and
      management of Lantana over two centuries and ask: Can we fight the spread of
      invasive species or do we need to develop strategies for their adaptive
      management? We carried out extensive research of historical records constituting
      over 75% of records on invasion and management of this species in the three
      countries. The records indicate that governments in Australia, India and South
      Africa have taken aggressive measures to eradicate Lantana over the last two
      centuries, but these efforts have been largely unsuccessful. We found that
      despite control measures, the invasion trajectory of Lantana has continued
      upwards and that post-war land-use change might have been a possible trigger for
      this spread. A large majority of studies on invasive species address timescales
      of less than one year; and even fewer address timescales of >10 years. An
      understanding of species invasions over long time-scales is of paramount
      importance. While archival records may give only a partial picture of the spread
      and management of invasive species, in the absence of any other long-term dataset
      on the ecology of Lantana, our study provides an important insight into its
      invasion, spread and management over two centuries and across three continents.
      While the established paradigm is to expend available resources on attempting to
      eradicate invasive species, our findings suggest that in the future,
      conservationists will need to develop strategies for their adaptive management
      rather than fighting a losing battle.

PMID- 22403654
TI  - Medication adherence in type 2 diabetes: the ENTRED study 2007, a French
      Population-Based Study.
AB  - BACKGROUND: Adherence to prescribed medications is a key dimension of healthcare
      quality. The aim of this large population-based study was to evaluate self
      reported medication adherence and to identify factors linked with poor adherence
      in patients with type 2 diabetes in France. METHODOLOGY: The ENTRED study 2007, a
      French national survey of people treated for diabetes, was based on a
      representative sample of patients who claimed reimbursement for oral
      hypoglycaemic agents and/or insulin at least three times between August 2006 and
      July 2007, and who were randomly selected from the database of the two main
      National Health Insurance Systems. Medication adherence was determined using a
      six-item self-administered questionnaire. A multinomial polychotomous logistic
      regression model was used to identify factors associated with medication
      adherence in the 3,637 persons with type 2 diabetes. PRINCIPAL FINDINGS: Thirty
      nine percent of patients reported good medication adherence, 49% medium adherence
      and 12% poor adherence. The factors significantly associated with poor adherence
      in multivariate analysis were socio-demographic factors: age <45 years, non
      European geographical origin, financial difficulties and being professionally
      active; disease and therapy-related factors: HbA(1c)>8% and existing diabetes
      complications; and health care-related factors: difficulties for taking
      medication alone, decision making by the patient only, poor acceptability of
      medical recommendations, lack of family or social support, need for information
      on treatment, reporting no confidence in the future, need for medical support and
      follow-up by a specialist physician. CONCLUSIONS: In a country with a high level
      of access to healthcare, our study demonstrated a substantial low level of
      medication adherence in type 2 diabetic patients. Better identification of those
      with poor adherence and individualised suitable recommendations remain essential
      for better healthcare management.

PMID- 22403655
TI  - Unexpected fine-scale population structure in a broadcast-spawning Antarctic
      marine mollusc.
AB  - Several recent empirical studies have challenged the prevailing dogma that
      broadcast-spawning species exhibit little or no population genetic structure by
      documenting genetic discontinuities associated with large-scale oceanographic
      features. However, relatively few studies have explored patterns of genetic
      differentiation over fine spatial scales. Consequently, we used a hierarchical
      sampling design to investigate the basis of a weak but significant genetic
      difference previously reported between Antarctic limpets (Nacella concinna)
      sampled from Adelaide and Galindez Islands near the base of the Antarctic
      Peninsula. Three sites within Ryder Bay, Adelaide Island (Rothera Point, Leonie
      and Anchorage Islands) were each sub-sampled three times, yielding a total of 405
      samples that were genotyped at 155 informative Amplified Fragment Length
      Polymorphisms (AFLPs). Contrary to our initial expectations, limpets from
      Anchorage Island were found to be subtly, but significantly distinct from those
      sampled from the other sites. This suggests that local processes may play an
      important role in generating fine-scale population structure even in species with
      excellent dispersal capabilities, and highlights the importance of sampling at
      multiple spatial scales in population genetic surveys.

PMID- 22403656
TI  - Dysregulation of gene expression in a lysosomal storage disease varies between
      brain regions implicating unexpected mechanisms of neuropathology.
AB  - The characteristic neurological feature of many neurogenetic diseases is
      intellectual disability. Although specific neuropathological features have been
      described, the mechanisms by which specific gene defects lead to cognitive
      impairment remain obscure. To gain insight into abnormal functions occurring
      secondary to a single gene defect, whole transcriptome analysis was used to
      identify molecular and cellular pathways that are dysregulated in the brain in a
      mouse model of a lysosomal storage disorder (LSD) (mucopolysaccharidosis [MPS]
      VII). We assayed multiple anatomical regions separately, in a large cohort of
      normal and diseased mice, which greatly increased the number of significant
      changes that could be detected compared to past studies in LSD models. We found
      that patterns of aberrant gene expression and involvement of multiple molecular
      and cellular systems varied significantly between brain regions. A number of
      changes revealed unexpected system and process alterations, such as up-regulation
      of the immune system with few inflammatory changes (a significant difference from
      the closely related MPS IIIb model), down-regulation of major oligodendrocyte
      genes even though white matter changes are not a feature histopathologically, and
      a plethora of developmental gene changes. The involvement of multiple neural
      systems indicates that the mechanisms of neuropathology in this type of disease
      are much broader than previously appreciated. In addition, the variation in gene
      dysregulation between brain regions indicates that different neuropathologic
      mechanisms may predominate within different regions of a diseased brain caused by
      a single gene mutation.

PMID- 22403657
TI  - Differential contribution of the repeats to heparin binding of HBHA, a major
      adhesin of Mycobacterium tuberculosis.
AB  - BACKGROUND: Tuberculosis remains one of the most important causes of global
      mortality and morbidity, and the molecular mechanisms of the pathogenesis are
      still incompletely understood. Only few virulence factors of the causative agent
      Mycobacterium tuberculosis are known. One of them is the heparin-binding
      haemagglutinin (HBHA), an important adhesin for epithelial cells and an
      extrapulmonary dissemination factor. HBHA mediates mycobacterial adherence to
      epithelial cells via the interactions of its C-terminal, lysine rich repeat
      domain with sulfated glycoconjugates on the surface of epithelial cells.
      METHODOLOGY/PRINCIPAL FINDINGS: Using defined heparin sulfate (HS) analogs, we
      determined the minimal heparin fragment length for HBHA binding and structural
      adaptations of the HBHA heparin-binding domain (HBD) upon binding to heparin. The
      NMR studies show significant shifts of all residues in the HBD upon interaction
      with heparin, with stronger shifts in the last repeats compared to the upstream
      repeats, and indicated that the HS fragments with 14 sugar units cover the entire
      C-terminal lysine-rich domain of HBHA. The differential implication of the
      repeats is determined by the relative position of prolines and lysines within
      each repeat, and may contribute to binding specificity. GAG binding induces a non
      homogeneous structural rearrangement in the HBD, with stabilization of a nascent
      alpha-helix only in the last penta-repeats. CONCLUSION/SIGNIFICANCE:
      Mycobacterial HBHA undergoes structural adaptation upon interaction with GAGs,
      which is likely involved in binding specificities of the adhesin, and
      mycobacterial pathogens may use HBD polymorphisms for host or organ specificity.
      Further studies will aim at decoding the complementarity between HBD repeats and
      HS sequence.

PMID- 22403658
TI  - Absence of association between N-acetyltransferase 2 acetylator status and
      colorectal cancer susceptibility: based on evidence from 40 studies.
AB  - BACKGROUND AND OBJECTIVES: N-Acetyltransferase (NAT) 2 is an important enzyme
      involved in the metabolism of different xenobiotics, including potential
      carcinogens, whose phenotypes were reported to be related to individual
      susceptibility to colorectal cancer (CRC). However, the results remain
      conflicting. To assess the relationship between NAT2 phenotypes and CRC risk, we
      performed this meta-analysis. METHODS: A comprehensive literature search was
      conducted to identify all case-control or cohort studies of NAT2 acetylator
      status on the susceptibility of CRC by searching of PubMed and EMBASE, up to May
      20, 2011. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used
      to assess the association. RESULTS: A total of over 40,000 subjects from 40
      published literatures were identified by searching the databases. No
      significantly elevated CRC risk in individuals with NAT2 slow acetylators
      compared with fast acetylators was found when all studies pooled (OR = 0.95, 95%
      CI: 0.87-1.04, I(2) = 52.6%). While three studies contributed to the source of
      heterogeneity were removed, there was still null result observed (OR = 0.96, 95%
      CI: 0.90-1.03, P = 0.17 for heterogeneity, I(2) = 17.8%). In addition, we failed
      to detect any associations in the stratified analyses by race, sex, source of
      controls, smoking status, genotyping methods or tumor localization. No
      publication bias was observed in this study. CONCLUSIONS: This meta-analysis
      suggests that the NAT2 phenotypes may not be associated with colorectal cancer
      development.

PMID- 22403659
TI  - Comparison of influenza and SIV specific CD8 T cell responses in macaques.
AB  - Macaques are a potentially useful non-human primate model to compare memory T
      cell immunity to acute virus pathogens such as influenza virus and effector T
      cell responses to chronic viral pathogens such as SIV. However, immunological
      reagents to study influenza CD8(+) T-cell responses in the macaque model are
      limited. We recently developed an influenza-SIV vaccination model of pigtail
      macaques (Macaca nemestrina) and used this to study both influenza-specific and
      SIV-specific CD8(+) T-cells in 39 pigtail macaques expressing the common Mane
      A*10(+) (Mane-A01*084) MHC-I allele. To perform comparative studies between
      influenza and SIV responses a common influenza nucleoprotein-specific CD8(+) T
      cell response was mapped to a minimal epitope (termed RA9), MHC-restricted to
      Mane-A*10 and an MHC tetramer developed to study this response. Influenza
      specific memory CD8(+) T-cell response maintained a highly functional profile in
      terms of multitude of effector molecule expression (CD107a, IFN-gamma, TNF-alpha,
      MIP-1beta and IL-2) and showed high avidity even in the setting of SIV infection.
      In contrast, within weeks following active SIV infection, SIV-specific CD8(+)
      effector T-cells expressed fewer cytokines/degranulation markers and had a lower
      avidity compared to influenza specific CD8(+) T-cells. Further, the influenza
      specific memory CD8 T-cell response retained stable expression of the exhaustion
      marker programmed death-marker-1 (PD-1) and co-stimulatory molecule CD28
      following infection with SIV. This contrasted with the effector SIV-specific
      CD8(+) T-cells following SIV infection which expressed significantly higher
      amounts of PD-1 and lower amounts of CD28. Our results suggest that strategies to
      maintain a more functional CD8(+) T-cell response, profile may assist in
      controlling HIV disease.

PMID- 22403660
TI  - Decreased neutrophil apoptosis in quiescent ANCA-associated systemic vasculitis.
AB  - BACKGROUND: ANCA-Associated Systemic Vasculitis (AASV) is characterized by
      leukocytoclasis, accumulation of unscavenged apoptotic and necrotic neutrophils
      in perivascular tissues. Dysregulation of neutrophil cell death may contribute
      directly to the pathogenesis of AASV. METHODS: Neutrophils from Healthy Blood
      Donors (HBD), patients with AASV most in complete remission, Polycythemia Vera
      (PV), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) and renal
      transplant recipients (TP) were incubated in vitro, and the rate of spontaneous
      apoptosis was measured by FACS. Plasma levels of cytokines and sFAS were measured
      with cytometric bead array and ELISA. Expression of pro/anti-apoptotic factors,
      transcription factors C/EBP-alpha, C/EBP-beta and PU.1 and inhibitors of
      survival/JAK2-pathway were measured by real-time-PCR. RESULTS: AASV, PV and RA
      neutrophils had a significantly lower rate of apoptosis compared to HBD
      neutrophils (AASV 50 +/- 14% vs. HBD 64 +/- 11%, p<0.0001). In RA but not in AASV
      and PV, low apoptosis rate correlated with increased plasma levels of GM-CSF and
      high mRNA levels of anti-apoptotic factors Bcl-2A1 and Mcl-1. AASV patients had
      normal levels of G-CSF, GM-CSF and IL-3. Both C/EBP-alpha, C/EBP-beta were
      significantly higher in neutrophils from AASV patients than HBD. Levels of sFAS
      were significantly higher in AASV compared to HBD. CONCLUSION: Neutrophil
      apoptosis rates in vitro are decreased in AASV, RA and PV but mechanisms seem to
      differ. Increased mRNA levels of granulopoiesis-associated transcription factors
      and increased levels of sFAS in plasma were observed in AASV. Additional studies
      are required to define the mechanisms behind the decreased apoptosis rates, and
      possible connections with accumulation of dying neutrophils in regions of
      vascular lesions in AASV patients.

PMID- 22403661
TI  - Bone marrow p16INK4a-deficiency does not modulate obesity, glucose homeostasis or
      atherosclerosis development.
AB  - OBJECTIVE: A genomic region near the CDKN2A locus, encoding p16(INK4a), has been
      associated to type 2 diabetes and atherosclerotic vascular disease, conditions in
      which inflammation plays an important role. Recently, we found that deficiency of
      p16(INK4a) results in decreased inflammatory signaling in murine macrophages and
      that p16(INK4a) influences the phenotype of human adipose tissue macrophages.
      Therefore, we investigated the influence of immune cell p16(INK4a) on glucose
      tolerance and atherosclerosis in mice. METHODS AND RESULTS: Bone marrow
      p16(INK4a)-deficiency in C57Bl6 mice did not influence high fat diet-induced
      obesity nor plasma glucose and lipid levels. Glucose tolerance tests showed no
      alterations in high fat diet-induced glucose intolerance. While bone marrow
      p16(INK4a)-deficiency did not affect the gene expression profile of adipose
      tissue, hepatic expression of the alternative markers Chi3l3, Mgl2 and IL10 was
      increased and the induction of pro-inflammatory Nos2 was restrained on the high
      fat diet. Bone marrow p16(INK4a)-deficiency in low density lipoprotein receptor
      deficient mice did not affect western diet-induced atherosclerotic plaque size or
      morphology. In line, plasma lipid levels remained unaffected and p16(INK4a)
      deficient macrophages displayed equal cholesterol uptake and efflux compared to
      wild type macrophages. CONCLUSION: Bone marrow p16(INK4a)-deficiency does not
      affect plasma lipids, obesity, glucose tolerance or atherosclerosis in mice.

PMID- 22403662
TI  - Generation of full-length cDNAs for eight putative GPCnR from the cattle tick, R.
      microplus using a targeted degenerate PCR and sequencing strategy.
AB  - We describe here a rapid and efficient method for the targeted isolation of
      specific members of gene families without the need for cloning. Using this
      strategy we isolated full length cDNAs for eight putative G-protein coupled
      neurotransmitter receptors (GPCnR) from the cattle tick Rhipicephalus (Boophilus)
      microplus. Gene specific degenerate primers were designed using aligned amino
      acid sequences of similar receptor types from several insect and arachnid
      species. These primers were used to amplify and sequence a section of the target
      gene. Rapid amplification of cDNA ends (RACE) PCR was used to generate full
      length cDNA sequences. Phylogenetic analysis placed 7 of these sequences into
      Class A G-protein coupled receptors (GPCR) (Rm_alpha2AOR, Rm_beta2AOR, Rm_Dop1R,
      Rm_Dop2R, Rm_INDR, Rm_5-HT(7)R and Rm_mAchR), and one into Class C GPCR
      (Rm_GABA(B)R). Of the 7 Class A sequences, only Rm_mAchR is not a member of the
      biogenic amine receptor family. The isolation of these putative receptor
      sequences provides an opportunity to gain an understanding of acaricide
      resistance mechanisms such as amitraz resistance and might suggest possibilities
      for the development of new acaricides.

PMID- 22403663
TI  - Interferon-gamma release assays for the diagnosis of tuberculosis and
      tuberculosis infection in HIV-infected adults: a systematic review and meta
      analysis.
AB  - BACKGROUND: Despite the widespread use of interferon-gamma release assays
      (IGRAs), their role in diagnosing tuberculosis and targeting preventive therapy
      in HIV-infected patients remains unclear. We conducted a comprehensive systematic
      review to contribute to the evidence-based practice in HIV-infected people.
      METHODOLOGY/PRINCIPAL FINDINGS: We searched MEDLINE, Cochrane, and Biomedicine
      databases to identify articles published between January 2005 and July 2011 that
      assessed QuantiFERON(r)-TB Gold In-Tube (QFT-GIT) and T-SPOT(r).TB (T-SPOT.TB) in
      HIV-infected adults. We assessed their accuracy for the diagnosis of tuberculosis
      and incident active tuberculosis, and the proportion of indeterminate results.
      The search identified 38 evaluable studies covering a total of 6514 HIV-infected
      participants. The pooled sensitivity and specificity for tuberculosis were 61%
      and 72% for QFT-GIT, and 65% and 70% for T-SPOT.TB. The cumulative incidence of
      subsequent active tuberculosis was 8.3% for QFT-GIT and 10% for T-SPOT.TB in
      patients tested positive (one study each), and 0% for QFT-GIT (two studies) and T
      SPOT.TB (one study) respectively in those tested negative. Pooled indeterminate
      rates were 8.2% for QFT-GIT and 5.9% for T-SPOT.TB. Rates were higher in high
      burden settings (12.0% for QFT-GIT and 7.7% for T-SPOT.TB) than in low
      intermediate burden settings (3.9% for QFT-GIT and 4.3% for T-SPOT.TB). They were
      also higher in patients with CD4(+) T-cell count <200 (11.6% for QFT-GIT and
      11.4% for T-SPOT.TB) than in those with CD4(+) T-cell count >= 200 (3.1% for QFT
      GIT and 7.9% for T-SPOT.TB). CONCLUSIONS/SIGNIFICANCE: IGRAs have suboptimal
      accuracy for confirming or ruling out active tuberculosis disease in HIV-infected
      adults. While their predictive value for incident active tuberculosis is modest,
      a negative QFT-GIT implies a very low short- to medium-term risk. Identifying the
      factors associated with indeterminate results will help to optimize the use of
      IGRAs in clinical practice, particularly in resource-limited countries with a
      high prevalence of HIV-coinfection.

PMID- 22403664
TI  - Using the RDP classifier to predict taxonomic novelty and reduce the search space
      for finding novel organisms.
AB  - BACKGROUND: Currently, the naive Bayesian classifier provided by the Ribosomal
      Database Project (RDP) is one of the most widely used tools to classify 16S rRNA
      sequences, mainly collected from environmental samples. We show that RDP has 97+%
      assignment accuracy and is fast for 250 bp and longer reads when the read
      originates from a taxon known to the database. Because most environmental samples
      will contain organisms from taxa whose 16S rRNA genes have not been previously
      sequenced, we aim to benchmark how well the RDP classifier and other competing
      methods can discriminate these novel taxa from known taxa. PRINCIPAL FINDINGS:
      Because each fragment is assigned a score (containing likelihood or confidence
      information such as the boostrap score in the RDP classifier), we "train" a
      threshold to discriminate between novel and known organisms and observe its
      performance on a test set. The threshold that we determine tends to be
      conservative (low sensitivity but high specificity) for naive Bayesian methods.
      Nonetheless, our method performs better with the RDP classifier than the other
      methods tested, measured by the f-measure and the area-under-the-curve on the
      receiver operating characteristic of the test set. By constraining the database
      to well-represented genera, sensitivity improves 3-15%. Finally, we show that the
      detector is a good predictor to determine novel abundant taxa (especially for
      finer levels of taxonomy where novelty is more likely to be present).
      CONCLUSIONS: We conclude that selecting a read-length appropriate RDP bootstrap
      score can significantly reduce the search space for identifying novel genera and
      higher levels in taxonomy. In addition, having a well-represented database
      significantly improves performance while having genera that are "highly" similar
      does not make a significant improvement. On a real dataset from an Amazon Terra
      Preta soil sample, we show that the detector can predict (or correlates to)
      whether novel sequences will be assigned to new taxa when the RDP database
      "doubles" in the future.

PMID- 22403665
TI  - Compositional development of Bifidobacterium and Lactobacillus microbiota is
      linked with crying and fussing in early infancy.
AB  - OBJECTIVES: Our aim was to establish whether there is an interconnection between
      the compositional development of the gut microbiota and the amount of fussing and
      crying in early infancy. METHODS: Behavioral patterns of 89 infants during the
      7(th) and 12(th) week of life were recorded in parental diaries. Total distress
      was defined as the sum of daily amounts of crying and fussing. Infants' gut
      microbiota profiles were investigated by several molecular assays during the
      first six months of life. RESULTS: The median (range) duration of total distress
      among the infants was 106 (0-478) minutes a day during the 7(th) and 58 (0-448)
      minutes a day during the 12(th) week. The proportion of Bifidobacterium counts to
      total bacterial counts was inversely associated with the amount of crying and
      fussing during the first 3 months of life (p = 0.03), although the number of
      Bifidobacterium breve was positively associated with total distress (p = 0.02).
      The frequency of Lactobacillus spp. at the age of 3 weeks was inversely
      associated with total infant distress during the 7(th) week of life (p = 0.02).
      CONCLUSIONS: Bifidobacterium and Lactobacillus appear to protect against crying
      and fussing. Identification of specific strains with optimal protective
      properties would benefit at-risk infants.

PMID- 22403666
TI  - eIF2alpha kinases regulate development through the BzpR transcription factor in
      Dictyostelium discoideum.
AB  - BACKGROUND: A major mechanism of translational regulation in response to a
      variety of stresses is mediated by phosphorylation of eIF2alpha to reduce
      delivery of initiator tRNAs to scanning ribosomes. For some mRNAs, often encoding
      a bZIP transcription factor, eIF2alpha phosphorylation leads to enhanced
      translation due to delayed reinitiation at upstream open reading frames.
      Dictyostelium cells possess at least three eIF2alpha kinases that regulate
      various portions of the starvation-induced developmental program. Cells
      possessing an eIF2alpha that cannot be phosphorylated (BS167) show abnormalities
      in growth and development. We sought to identify a bZIP protein in Dictyostelium
      whose production is controlled by the eIF2alpha regulatory system. PRINCIPAL
      FINDINGS: Cells disrupted in the bzpR gene had similar developmental defects as
      BS167 cells, including small entities, stalk defects, and reduced spore
      viability. beta-galactosidase production was used to examine translation from
      mRNA containing the bzpR 5' UTR. While protein production was readily apparent
      and regulated temporally and spatially in wild type cells, essentially no beta
      galactosidase was produced in developing BS167 cells even though the lacZ mRNA
      levels were the same as those in wild type cells. Also, no protein production was
      observed in strains lacking IfkA or IfkB eIF2alpha kinases. GFP fusions, with
      appropriate internal controls, were used to directly demonstrate that the bzpR 5'
      UTR, possessing 7 uORFs, suppressed translation by 12 fold. Suppression occurred
      even when all but one uORF was deleted, and translational suppression was removed
      when the ATG of the single uORF was mutated. CONCLUSIONS: The findings indicate
      that BzpR regulates aspects of the development program in Dictyostelium, serving
      as a downstream effector of eIF2alpha phosphorylation. Its production is
      temporally and spatially regulated by eIF2alpha phosphorylation by IfkA and IfkB
      and through the use of uORFs within the bzpR 5' UTR.

PMID- 22403667
TI  - Genomic heterogeneity in a natural archaeal population suggests a model of tRNA
      gene disruption.
AB  - Understanding the mechanistic basis of the disruption of tRNA genes, as
      manifested in the intron-containing and split tRNAs found in Archaea, will
      provide considerable insight into the evolution of the tRNA molecule. However,
      the evolutionary processes underlying these disruptions have not yet been
      identified. Previously, a composite genome of the deep-branching archaeon
      Caldiarchaeum subterraneum was reconstructed from a community genomic library
      prepared from a C. subterraneum-dominated microbial mat. Here, exploration of
      tRNA genes from the library reveals that there are at least three types of
      heterogeneity at the tRNA(Thr)(GGU) gene locus in the Caldiarchaeum population.
      All three involve intronic gain and splitting of the tRNA gene. Of two fosmid
      clones found that encode tRNA(Thr)(GGU), one (tRNA(Thr-I)) contains a single
      intron, whereas another (tRNA(Thr-II)) contains two introns. Notably, in the
      clone possessing tRNA(Thr-II), a 5' fragment of the tRNA(Thr-I) (tRNA(Thr-F))
      gene was observed 1.8-kb upstream of tRNA(Thr-II). The composite genome contains
      both tRNA(Thr-II) and tRNA(Thr-F), although the loci are >500 kb apart. Given
      that the 1.8-kb sequence flanked by tRNA(Thr-F) and tRNA(Thr-II) is predicted to
      encode a DNA recombinase and occurs in six regions of the composite genome, it
      may be a transposable element. Furthermore, its dinucleotide composition is most
      similar to that of the pNOB8-type plasmid, which is known to integrate into
      archaeal tRNA genes. Based on these results, we propose that the gain of the tRNA
      intron and the scattering of the tRNA fragment occurred within a short time frame
      via the integration and recombination of a mobile genetic element.

PMID- 22403668
TI  - Construction of a baculovirus-silkworm multigene expression system and its
      application on producing virus-like particles.
AB  - A new baculovirus-silkworm multigene expression system named Bombyx mori MultiBac
      is developed and described here, by which multiple expression cassettes can be
      introduced into the Bombyx mori nuclear polyhedrosis virus (BmNPV) genome
      efficiently. The system consists of three donor vectors (pCTdual, pRADM and
      pUCDMIG) and an invasive diaminopimelate (DAP) auxotrophic recipient E. coli
      containing BmNPV-Bacmid (BmBacmid) with a homologous recombination region, an
      attTn7 site and a loxp site. Two genes carried by pCTdual are firstly inserted
      into BmBacmid by homologous recombination, while the other eight genes in pRADM
      and pUCDMIG are introduced into BmBacmid through Tn7 transposition and cre-loxp
      recombination. Then the invasive and DAP auxotrophic E. coli carrying recombinant
      BmBacmid is directly injected into silkworm for expressing heterologous genes in
      larvae or pupae. Three structural genes of rotavirus and three fluorescent genes
      have been simultaneously expressed in silkworm larvae using our new system,
      resulting in the formation of virus-like particles (VLPs) of rotavirus and the
      color change of larvae. The VLPs were purified from hemolymph by
      ultracentrifugation using CsCl gradients, with a yield of 12.7 ug per larva. For
      the great capacity of foreign genes and the low cost of feeding silkworm, this
      high efficient BmMultiBac expression system provides a suitable platform to
      produce VLPs or protein complexes.

PMID- 22403670
TI  - Differential response to soil salinity in endangered key tree cactus:
      implications for survival in a changing climate.
AB  - Understanding reasons for biodiversity loss is essential for developing
      conservation and management strategies and is becoming increasingly urgent with
      climate change. Growing at elevations <1.4 m in the Florida Keys, USA, the
      endangered Key tree cactus (Pilosocereus robinii) experienced 84 percent loss of
      total stems from 1994 to 2007. The most severe losses of 99 and 88 percent stems
      occurred in the largest populations in the Lower Keys, where nine storms with
      high wind velocities and storm surges, occurred during this period. In contrast,
      three populations had substantial stem proliferation. To evaluate possible
      mortality factors related to changes in climate or forest structure, we examined
      habitat variables: soil salinity, elevation, canopy cover, and habitat structure
      near 16 dying or dead and 18 living plants growing in the Lower Keys. Soil
      salinity and elevation were the preliminary factors that discriminated live and
      dead plants. Soil salinity was 1.5 times greater, but elevation was 12 cm higher
      near dead plants than near live plants. However, distribution-wide stem loss was
      not significantly related to salinity or elevation. Controlled salinity trials
      indicated that salt tolerance to levels above 40 mM NaCl was related to maternal
      origin. Salt sensitive plants from the Lower Keys had less stem growth, lower
      root:shoot ratios, lower potassium: sodium ratios and lower recovery rate, but
      higher delta (13)C than a salt tolerant lineage of unknown origin. Unraveling the
      genetic structure of salt tolerant and salt sensitive lineages in the Florida
      Keys will require further genetic tests. Worldwide rare species restricted to
      fragmented, low-elevation island habitats, with little or no connection to higher
      ground will face challenges from climate change-related factors. These great
      conservation challenges will require traditional conservation actions and
      possibly managed relocation that must be informed by studies such as these.

PMID- 22403669
TI  - The impact of point mutations in the human androgen receptor: classification of
      mutations on the basis of transcriptional activity.
AB  - Androgen receptor mediated signaling drives prostate cancer cell growth and
      survival. Mutations within the receptor occur infrequently in prostate cancer
      prior to hormonal therapy but become prevalent in incurable androgen independent
      and metastatic tumors. Despite the determining role played by the androgen
      receptor in all stages of prostate cancer progression, there is a conspicuous
      dearth of comparable data on the consequences of mutations. In order to remedy
      this omission, we have combined an expansive study of forty five mutations which
      are predominantly associated with high Gleason scores and metastatic tumors, and
      span the entire length of the receptor, with a literature review of the mutations
      under investigation. We report the discovery of a novel prevalent class of
      androgen receptor mutation that possesses loss of function at low levels of
      androgen yet transforms to a gain of function at physiological levels.
      Importantly, mutations introducing constitutive gain of function are uncommon,
      with the majority of mutations leading to either loss of function or no
      significant change from wild-type activity. Therefore, the widely accepted
      supposition that androgen receptor mutations in prostate cancer result in gain of
      function is appealing, but mistaken. In addition, the transcriptional outcome of
      some mutations is dependent upon the androgen receptor responsive element. We
      discuss the consequences of these findings and the role of androgen receptor
      mutations for prostate cancer progression and current treatment options.

PMID- 22403671
TI  - Internal wave turbulence near a Texel beach.
AB  - A summer bather entering a calm sea from the beach may sense alternating warm and
      cold water. This can be felt when moving forward into the sea ('vertically
      homogeneous' and 'horizontally different'), but also when standing still between
      one's feet and body ('vertically different'). On a calm summer-day, an array of
      high-precision sensors has measured fast temperature-changes up to 1  degrees C
      near a Texel-island (NL) beach. The measurements show that sensed variations are
      in fact internal waves, fronts and turbulence, supported in part by vertical
      stable stratification in density (temperature). Such motions are common in the
      deep ocean, but generally not in shallow seas where turbulent mixing is expected
      strong enough to homogenize. The internal beach-waves have amplitudes ten-times
      larger than those of the small surface wind waves. Quantifying their turbulent
      mixing gives diffusivity estimates of 10(-4)-10(-3) m(2) s(-1), which are larger
      than found in open-ocean but smaller than wave breaking above deep sloping
      topography.

PMID- 22403672
TI  - Morbidity and risk of subsequent diagnosis of HIV: a population based case
      control study identifying indicator diseases for HIV infection.
AB  - BACKGROUND: Early identification of persons with undiagnosed HIV infection is an
      important health care issue. We examined associations between diseases diagnosed
      in hospitals and risk of subsequent HIV diagnosis. METHODS: In this population
      based case control study, cases were persons with incident HIV infection
      diagnosed in Denmark between 1 January 1995 and 1 June 2008. Risk-set sampling
      was used to identify 19 age- and gender-matched population controls for each HIV
      case, using the HIV diagnosis date as the index date for both cases and controls.
      Prior hospital diagnoses obtained from Danish medical databases were first
      categorized into 22 major disease categories (excluding AIDS-defining diseases
      except tuberculosis) and then subdivided into 161 subcategories, allowing us to
      examine specific diseases as potential HIV indicators by conditional logistic
      regression. RESULTS: The study included 2,036 HIV cases and 35,718 controls.
      Persons with the following disease categories had a high risk of HIV diagnosis
      during the subsequent 5-year period: sexually transmitted infections and viral
      hepatitis (adjusted odds ratio [aOR] = 12.3, 95% CI: 9.60-15.7), hematological
      diseases (aOR = 4.28, 3.13-5.85), lower respiratory tract infections (aOR = 3.98,
      3.14-5.04)), CNS infections (aOR = 3.44, 1.74-6.80), skin infections (aOR = 3.05,
      2.47-3.75), other infections (aOR = 4.64, 3.89-5.54), and substance abuse (aOR =
      2.60, 2.06-3.29). Several specific diseases were associated with aORs >20
      including syphilis, hepatitis A, non "A" viral hepatitis, herpes zoster, candida
      infection, endocarditis, thrombocytopenia, and opioid abuse. CONCLUSIONS:
      Targeted testing for HIV in patients diagnosed with diseases associated with HIV
      may lead to earlier treatment and thereby reduced morbidity, mortality and HIV
      transmission.

PMID- 22403673
TI  - Crystallization and preliminary analysis of crystals of the 24-meric hemocyanin
      of the emperor scorpion (Pandinus imperator).
AB  - Hemocyanins are giant oxygen transport proteins found in the hemolymph of several
      invertebrate phyla. They constitute giant multimeric molecules whose size range
      up to that of cell organelles such as ribosomes or even small viruses. Oxygen is
      reversibly bound by hemocyanins at binuclear copper centers. Subunit interactions
      within the multisubunit hemocyanin complex lead to diverse allosteric effects
      such as the highest cooperativity for oxygen binding found in nature. Crystal
      structures of a native hemocyanin oligomer larger than a hexameric substructure
      have not been published until now. We report for the first time growth and
      preliminary analysis of crystals of the 24-meric hemocyanin (M(W) = 1.8 MDa) of
      emperor scorpion (Pandinus imperator), which diffract to a resolution of 6.5 A.
      The crystals are monoclinc with space group C 1 2 1 and cell dimensions a =
      311.61 A, b = 246.58 A and c = 251.10 A (alpha = 90.00 degrees , beta = 90.02
      degrees , gamma = 90.00 degrees ). The asymmetric unit contains one molecule of
      the 24-meric hemocyanin and the solvent content of the crystals is 56%. A
      preliminary analysis of the hemocyanin structure reveals that emperor scorpion
      hemocyanin crystallizes in the same oxygenated conformation, which is also
      present in solution as previously shown by cryo-EM reconstruction and small angle
      x-ray scattering experiments.

PMID- 22403674
TI  - Gender-divergent profile of bile acid homeostasis during aging of mice.
AB  - Aging is a physiological process with a progressive decline of adaptation and
      functional capacity of the body. Bile acids (BAs) have been recognized as
      signaling molecules regulating the homeostasis of glucose, lipid, and energy. The
      current study characterizes the age-related changes of individual BA
      concentrations by ultra-performance liquid chromatography-tandem mass
      spectrometry (UPLC-MS/MS) in serum and liver of male and female C57BL/6 mice from
      3 to 27 months of age. Total BA concentrations in serum increased 340% from 3 to
      27 months in female mice, whereas they remained relatively constant with age in
      male mice. During aging, male and female mice shared the following changes: (1)
      BA concentrations in liver remained relatively constant; (2) the proportions of
      beta-muricholic acid (betaMCA) increased and deoxycholic acid (DCA) decreased
      between 3 and 27 months in serum and liver; and (3) total BAs in serum and liver
      became more hydrophilic between 3 and 27 months. In female mice, (1) the mRNAs of
      hepatic BA uptake transporters, the Na(+)/taurocholate cotransporting polypeptide
      (Ntcp) and the organic anion transporting polypeptide 1b2 (Oatp1b2), decreased
      after 12 months, and similar trends were observed for their proteins; (2) the
      mRNA of the rate-limiting enzyme for BA synthesis, cholesterol 7alpha-hydroxylase
      (Cyp7a1), increased from 3 to 9 months and remained high thereafter. However, in
      male mice, Ntcp, Oatp1b2, and Cyp7a1 mRNAs remained relatively constant with age.
      In summary, the current study shows gender-divergent profiles of BA
      concentrations and composition in serum and liver of mice during aging, which is
      likely due to the gender-divergent expression of BA transporters Ntcp and Oatp1b2
      as well as the synthetic enzyme Cyp7a1.

PMID- 22403675
TI  - In vivo gene knockdown in rat dorsal root ganglia mediated by self-complementary
      adeno-associated virus serotype 5 following intrathecal delivery.
AB  - We report here in adult rat viral vector mediate-gene knockdown in the primary
      sensory neurons and the associated cellular and behavior consequences. Self
      complementary adeno-associated virus serotype 5 (AAV5) was constructed to express
      green fluorescent protein (GFP) and a small interfering RNA (siRNA) targeting
      mammalian target of rapamycin (mTOR). The AAV vectors were injected via an
      intrathecal catheter. We observed profound GFP expression in lumbar DRG neurons
      beginning at 2-week post-injection. Of those neurons, over 85% were large to
      medium-diameter and co-labeled with NF200, a marker for myelinated fibers.
      Western blotting of mTOR revealed an 80% reduction in the lumbar DRGs (L4-L6) of
      rats treated with the active siRNA vectors compared to the control siRNA vector.
      Gene knockdown became apparent as early as 7-day post-injection and lasted for at
      least 5 weeks. Importantly, mTOR knockdown occurred in large (NF200) and small
      diameter neurons (nociceptors). The viral administration induced an increase of
      Iba1 immunoreactivity in the DRGs, which was likely attributed to the expression
      of GFP but not siRNA. Rats with mTOR knockdown in DRG neurons showed normal
      general behavior and unaltered responses to noxious stimuli. In conclusion,
      intrathecal AAV5 is a highly efficient vehicle to deliver siRNA and generate gene
      knockdown in DRG neurons. This will be valuable for both basic research and
      clinic intervention of diseases involving primary sensory neurons.

PMID- 22403676
TI  - Use of sensitive, broad-spectrum molecular assays and human airway epithelium
      cultures for detection of respiratory pathogens.
AB  - Rapid and accurate detection and identification of viruses causing respiratory
      tract infections is important for patient care and disease control. Despite the
      fact that several assays are available, identification of an etiological agent is
      not possible in ~30% of patients suffering from respiratory tract diseases.
      Therefore, the aim of the current study was to develop a diagnostic set for the
      detection of respiratory viruses with sensitivity as low as 1-10 copies per
      reaction. Evaluation of the assay using a training clinical sample set showed
      that viral nucleic acids were identified in ~76% of cases. To improve assay
      performance and facilitate the identification of novel species or emerging
      strains, cultures of fully differentiated human airway epithelium were used to
      pre-amplify infectious viruses. This additional step resulted in the detection of
      pathogens in all samples tested. Based on these results it can be hypothesized
      that the lack of an etiological agent in some clinical samples, both reported
      previously and observed in the present study, may result not only from the
      presence of unknown viral species, but also from imperfections in the detection
      methods used.

PMID- 22403677
TI  - High fat diet alters lactation outcomes: possible involvement of inflammatory and
      serotonergic pathways.
AB  - Delay in the onset of lactogenesis has been shown to occur in women who are
      obese, however the mechanism altered within the mammary gland causing the delay
      remains unknown. Consumption of high fat diets (HFD) has been previously
      determined to result decreased litters and litter numbers in rodent models due to
      a decrease in fertility. We examined the effects of feeding a HFD (60% kcal from
      fat) diet versus a low-fat diet (LFD; 10% kcal from fat) to female Wistar rats on
      lactation outcomes. Feeding of HFD diet resulted in increased pup weights
      compared to pups from LFD fed animals for 4 d post-partum. Lactation was delayed
      in mothers on HFD but they began to produce copious milk volumes beginning 2 d
      post-partum, and milk yield was similar to LFD by day 3. Mammary glands collected
      from lactating animals on HFD diet, displayed a disrupted morphologies, with very
      few and small alveoli. Consistently, there was a significant decrease in the mRNA
      expression of milk protein genes, glucose transporter 1 (GLUT1) and keratin 5
      (K5), a luminobasal cell marker in the mammary glands of HFD lactating animals.
      Expression of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in
      serotonin (5-HT) biosynthesis, and the 5-HT(7) receptor (HTR7), which regulates
      mammary gland involution, were significantly increased in mammary glands of HFD
      animals. Additionally, we saw elevation of the inflammatory markers interleukin-6
      (IL-6) and tumor necrosis factor-alpha (TNF- alpha). These results indicate that
      consumption of HFD impairs mammary parenchymal tissue and impedes its ability to
      synthesize and secrete milk, possibly through an increase in 5-HT production
      within the mammary gland leading to an inflammatory process.

PMID- 22403678
TI  - Biophysical property and broad anti-HIV activity of albuvirtide, a 3
      maleimimidopropionic acid-modified peptide fusion inhibitor.
AB  - Albuvirtide (ABT) is a 3-maleimimidopropionic acid (MPA)-modified peptide HIV
      fusion inhibitor that can irreversibly conjugate to serum albumin. Previous
      studies demonstrated its in vivo long half-life and potent anti-HIV activity.
      Here, we focused to characterize its biophysical properties and evaluate its
      antiviral spectrum. In contrast to T20 (Enfuvirtide, Fuzeon), ABT was able to
      form a stable alpha-helical conformation with the target sequence and block the
      fusion-active six-helix bundle (6-HB) formation in a dominant-negative manner. It
      efficiently inhibited HIV-1 Env-mediated cell membrane fusion and virus entry. A
      large panel of 42 HIV-1 pseudoviruses with different genotypes were constructed
      and used for the antiviral evaluation. The results showed that ABT had potent
      inhibitory activity against the subtypes A, B and C that predominate the
      worldwide AIDS epidemics, and subtype B', CRF07_BC and CRF01_AE recombinants that
      are currently circulating in China. Furthermore, ABT was also highly effective
      against HIV-1 variants resistant to T20. Taken together, our data indicate that
      the chemically modified peptide ABT can serve as an ideal HIV-1 fusion inhibitor.

PMID- 22403679
TI  - Cell-specific DNA methylation patterns of retina-specific genes.
AB  - Many studies have demonstrated that epigenetic mechanisms are important in the
      regulation of gene expression during embryogenesis, gametogenesis, and other
      forms of tissue-specific gene regulation. We sought to explore the possible role
      of epigenetics, specifically DNA methylation, in the establishment and
      maintenance of cell type-restricted gene expression in the retina. To assess the
      relationship between DNA methylation status and expression level of retinal
      genes, bisulfite sequence analysis of the 1000 bp region around the transcription
      start sites (TSS) of representative rod and cone photoreceptor-specific genes and
      gene expression analysis were performed in the WERI and Y79 human retinoblastoma
      cell lines. Next, the homologous genes in mouse were bisulfite sequenced in the
      retina and in non-expressing tissues. Finally, bisulfite sequencing was performed
      on isolated photoreceptor and non-photoreceptor retinal cells isolated by laser
      capture microdissection. Differential methylation of rhodopsin (RHO), retinal
      binding protein 3 (RBP3, IRBP) cone opsin, short-wave-sensitive (OPN1SW), cone
      opsin, middle-wave-sensitive (OPN1MW), and cone opsin, long-wave-sensitive
      (OPN1LW) was found in the retinoblastoma cell lines that inversely correlated
      with gene expression levels. Similarly, we found tissue-specific hypomethylation
      of the promoter region of Rho and Rbp3 in mouse retina as compared to non
      expressing tissues, and also observed hypomethylation of retinal-expressed
      microRNAs. The Rho and Rbp3 promoter regions were unmethylated in expressing
      photoreceptor cells and methylated in non-expressing, non-photoreceptor cells
      from the inner nuclear layer. A third regional hypomethylation pattern of
      photoreceptor-specific genes was seen in a subpopulation of non-expressing
      photoreceptors (Rho in cones from the Nrl -/- mouse and Opn1sw in rods). These
      results demonstrate that a number of photoreceptor-specific genes have cell
      specific differential DNA methylation that correlates inversely with their
      expression level. Furthermore, these cell-specific patterns suggest that DNA
      methylation may play an important role in modulating photoreceptor gene
      expression in the developing mammalian retina.

PMID- 22403680
TI  - Efficient generation of lens progenitor cells from cataract patient-specific
      induced pluripotent stem cells.
AB  - The development of a technique to induce the transformation of somatic cells to a
      pluripotent state via the ectopic expression of defined transcription factors was
      a transformational event in the field of regenerative medicine. The development
      of this technique also impacted ophthalmology, as patient-specific induced
      pluripotent stemcells (iPSCs) may be useful resources for some ophthalmological
      diseases. The lens is a key refractive element in the eye that focuses images of
      the visual world onto the retina. To establish a new model for drug screening to
      treat lens diseases and investigating lens aging and development, we examined
      whether human lens epithelial cells (HLECs) could be induced into iPSCs and if
      lens-specific differentiation of these cells could be achieved under defined
      chemical conditions. We first efficiently reprogrammed HLECs from age-related
      cataract patients to iPSCs with OCT-4, SOX-2, and KLF-4. The resulting HLEC
      derived iPS (HLE-iPS) colonies were indistinguishable from human ES cells with
      respect to morphology, gene expression, pluripotent marker expression and their
      ability to generate all embryonic germ-cell layers. Next, we performed a 3-step
      induction procedure: HLE-iPS cells were differentiated into large numbers of lens
      progenitor-like cells with defined factors (Noggin, BMP and FGF2), and we
      determined that these cells expressed lens-specific markers (PAX6, SOX2, SIX3,
      CRYAB, CRYAA, BFSP1, and MIP). In addition, HLE-iPS-derived lens cells exhibited
      reduced expression of epithelial mesenchymal transition (EMT) markers compared
      with human embryonic stem cells (hESCs) and fibroblast-derived iPSCs. Our study
      describes a highly efficient procedure for generating lens progenitor cells from
      cataract patient HLEC-derived iPSCs. These patient-derived pluripotent cells
      provide a valuable model for studying the developmental and molecular biological
      mechanisms that underlie cell determination in lens development and cataract
      pathophysiology.

PMID- 22403681
TI  - Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential
      use in Alzheimer's disease.
AB  - Alzheimer's disease is a growing concern in the modern world. As the currently
      available medications are not very promising, there is an increased need for the
      fabrication of newer drugs. Curcumin is a plant derived compound which has
      potential activities beneficial for the treatment of Alzheimer's disease. Anti
      amyloid activity and anti-oxidant activity of curcumin is highly beneficial for
      the treatment of Alzheimer's disease. The insolubility of curcumin in water
      restricts its use to a great extend, which can be overcome by the synthesis of
      curcumin nanoparticles. In our work, we have successfully synthesized water
      soluble PLGA coated- curcumin nanoparticles and characterized it using different
      techniques. As drug targeting to diseases of cerebral origin are difficult due to
      the stringency of blood-brain barrier, we have coupled the nanoparticle with Tet
      1 peptide, which has the affinity to neurons and possess retrograde
      transportation properties. Our results suggest that curcumin encapsulated-PLGA
      nanoparticles are able to destroy amyloid aggregates, exhibit anti-oxidative
      property and are non-cytotoxic. The encapsulation of the curcumin in PLGA does
      not destroy its inherent properties and so, the PLGA-curcumin nanoparticles can
      be used as a drug with multiple functions in treating Alzheimer's disease proving
      it to be a potential therapeutic tool against this dreaded disease.

PMID- 22403682
TI  - A modified method for whole exome resequencing from minimal amounts of starting
      DNA.
AB  - Next generation DNA sequencing (NGS) technologies have revolutionized the pace at
      which whole genome and exome sequences can be generated. However, despite these
      advances, many of the methods for targeted resequencing, such as the generation
      of high-depth exome sequences, are somewhat limited by the relatively large
      amounts of starting DNA that are normally required. In the case of tumour
      analysis this is particularly pertinent as many tumour biopsies often return
      submicrogram quantities of DNA, especially when tumours are microdissected prior
      to analysis. Here, we present a method for exome capture and resequencing using
      as little as 50 ng of starting DNA. The sequencing libraries generated by this
      minimal starting amount (MSA-Cap) method generate datasets that are comparable to
      standard amount (SA) whole exome libraries that use three micrograms of starting
      DNA. This method, which can be performed in most laboratories using commonly
      available reagents, has the potential to enhance large scale profiling efforts
      such as the resequencing of tumour exomes.

PMID- 22403683
TI  - Evidence for the contribution of the hemozoin synthesis pathway of the murine
      Plasmodium yoelii to the resistance to artemisinin-related drugs.
AB  - Plasmodium falciparum malaria is a major global health problem, causing
      approximately 780,000 deaths each year. In response to the spreading of P.
      falciparum drug resistance, WHO recommended in 2001 to use artemisinin
      derivatives in combination with a partner drug (called ACT) as first-line
      treatment for uncomplicated falciparum malaria, and most malaria-endemic
      countries have since changed their treatment policies accordingly. Currently, ACT
      are often the last treatments that can effectively and rapidly cure P. falciparum
      infections permitting to significantly decrease the mortality and the morbidity
      due to malaria. However, alarming signs of emerging resistance to artemisinin
      derivatives along the Thai-Cambodian border are of major concern. Through long
      term in vivo pressures, we have been able to select a murine malaria model
      resistant to artemisinins. We demonstrated that the resistance of Plasmodium to
      artemisinin-based compounds depends on alterations of heme metabolism and on a
      loss of hemozoin formation linked to the down-expression of the recently
      identified Heme Detoxification Protein (HDP). These artemisinins resistant
      strains could be able to detoxify the free heme by an alternative catabolism
      pathway involving glutathione (GSH)-mediation. Finally, we confirmed that
      artemisinins act also like quinolines against Plasmodium via hemozoin production
      inhibition. The work proposed here described the mechanism of action of this
      class of molecules and the resistance to artemisinins of this model. These
      results should help both to reinforce the artemisinins activity and avoid
      emergence and spread of endoperoxides resistance by focusing in adequate drug
      partners design. Such considerations appear crucial in the current context of
      early artemisinin resistance in Asia.

PMID- 22403684
TI  - Estimating the burden of malaria in Senegal: Bayesian zero-inflated binomial
      geostatistical modeling of the MIS 2008 data.
AB  - The Research Center for Human Development in Dakar (CRDH) with the technical
      assistance of ICF Macro and the National Malaria Control Programme (NMCP)
      conducted in 2008/2009 the Senegal Malaria Indicator Survey (SMIS), the first
      nationally representative household survey collecting parasitological data and
      malaria-related indicators. In this paper, we present spatially explicit
      parasitaemia risk estimates and number of infected children below 5 years.
      Geostatistical Zero-Inflated Binomial models (ZIB) were developed to take into
      account the large number of zero-prevalence survey locations (70%) in the data.
      Bayesian variable selection methods were incorporated within a geostatistical
      framework in order to choose the best set of environmental and climatic
      covariates associated with the parasitaemia risk. Model validation confirmed that
      the ZIB model had a better predictive ability than the standard Binomial
      analogue. Markov chain Monte Carlo (MCMC) methods were used for inference.
      Several insecticide treated nets (ITN) coverage indicators were calculated to
      assess the effectiveness of interventions. After adjusting for climatic and socio
      economic factors, the presence of at least one ITN per every two household
      members and living in urban areas reduced the odds of parasitaemia by 86% and 81%
      respectively. Posterior estimates of the ORs related to the wealth index show a
      decreasing trend with the quintiles. Infection odds appear to be increasing with
      age. The population-adjusted prevalence ranges from 0.12% in Thille-Boubacar to
      13.1% in Dabo. Tambacounda has the highest population-adjusted predicted
      prevalence (8.08%) whereas the region with the highest estimated number of
      infected children under the age of 5 years is Kolda (13940). The contemporary map
      and estimates of malaria burden identify the priority areas for future control
      interventions and provide baseline information for monitoring and evaluation.
      Zero-Inflated formulations are more appropriate in modeling sparse geostatistical
      survey data, expected to arise more frequently as malaria research is focused on
      elimination.

PMID- 22403685
TI  - HIV and STI prevalence among female sex workers in Cote d'Ivoire: why targeted
      prevention programs should be continued and strengthened.
AB  - OBJECTIVE: To assess condom use and prevalence of STIs and HIV among female sex
      workers (FSWs), as part of a comprehensive monitoring and evaluation plan of a
      nationwide sex worker prevention project in Cote d'Ivoire. DESIGN AND METHODS:
      Cross sectional surveys were conducted among FSWs attending five project clinics
      in Abidjan and San Pedro (2007), and in Yamoussoukro and Gagnoa (2009). A
      standardized questionnaire was administered in a face-to-face interview, which
      included questions on socio-demographic characteristics, sexual behaviour and
      condom use. After the interview, the participants were asked to provide samples
      for STI and HIV testing. RESULTS: A total of 1110 FSWs participated in the
      surveys. There were large differences in socio-demographic and behavioural
      characteristics between FSW coming for the first time as compared to FSW coming
      on a routine visit. The prevalence of N. gonorrhoeae or C.trachomatis was 9.1%,
      11.8% among first vs. 6.9% routine attendees (p = 0.004). The overall HIV
      prevalence was 26.6%, it was lower among first time attendees (17.5% as compared
      to 33.9% for routine attendees, p<0.001). The HIV prevalence among first
      attendees was also lower than the proportion of HIV positive tests from routine
      testing and counselling services in the same clinics. CONCLUSIONS: The results
      show a relatively high STI and HIV prevalence among FSWs in different cities in
      Cote d'Ivoire. In the light of these results, prevention efforts should continue
      to focus on FSWs in the country.

PMID- 22403686
TI  - DJ-1 null dopaminergic neuronal cells exhibit defects in mitochondrial function
      and structure: involvement of mitochondrial complex I assembly.
AB  - DJ-1 is a Parkinson's disease-associated gene whose protein product has a
      protective role in cellular homeostasis by removing cytosolic reactive oxygen
      species and maintaining mitochondrial function. However, it is not clear how DJ-1
      regulates mitochondrial function and why mitochondrial dysfunction is induced by
      DJ-1 deficiency. In a previous study we showed that DJ-1 null dopaminergic
      neuronal cells exhibit defective mitochondrial respiratory chain complex I
      activity. In the present article we investigated the role of DJ-1 in complex I
      formation by using blue native-polyacrylamide gel electrophoresis and 2
      dimensional gel analysis to assess native complex status. On the basis of these
      experiments, we concluded that DJ-1 null cells have a defect in the assembly of
      complex I. Concomitant with abnormal complex I formation, DJ-1 null cells show
      defective supercomplex formation. It is known that aberrant formation of the
      supercomplex impairs the flow of electrons through the channels between
      respiratory chain complexes, resulting in mitochondrial dysfunction. We took two
      approaches to study these mitochondrial defects. The first approach assessed the
      structural defect by using both confocal microscopy with MitoTracker staining and
      electron microscopy. The second approach assessed the functional defect by
      measuring ATP production, O(2) consumption, and mitochondrial membrane potential.
      Finally, we showed that the assembly defect as well as the structural and
      functional abnormalities in DJ-1 null cells could be reversed by adenovirus
      mediated overexpression of DJ-1, demonstrating the specificity of DJ-1 on these
      mitochondrial properties. These mitochondrial defects induced by DJ-1mutation may
      be a pathological mechanism for the degeneration of dopaminergic neurons in
      Parkinson's disease.

PMID- 22403687
TI  - Reducing false-positive prediction of minimotifs with a genetic interaction
      filter.
AB  - BACKGROUND: Minimotifs are short contiguous peptide sequences in proteins that
      have known functions. At its simplest level, the minimotif sequence is present in
      a source protein and has an activity relationship with a target, most of which
      are proteins. While many scientists routinely investigate new minimotif functions
      in proteins, the major web-based discovery tools have a high rate of false
      positive prediction. Any new approach that reduces false-positives will be of
      great help to biologists. METHODS AND FINDINGS: We have built three filters that
      use genetic interactions to reduce false-positive minimotif predictions. The
      basic filter identifies those minimotifs where the source/target protein pairs
      have a known genetic interaction. The HomoloGene genetic interaction filter
      extends these predictions to predicted genetic interactions of orthologous
      proteins and the node-based filter identifies those minimotifs where proteins
      that have a genetic interaction with the source or target have a genetic
      interaction. Each filter was evaluated with a test data set containing thousands
      of true and false-positives. Based on sensitivity and selectivity performance
      metrics, the basic filter had the best discrimination for true positives, whereas
      the node-based filter had the highest sensitivity. We have implemented these
      genetic interaction filters on the Minimotif Miner 2.3 website. The genetic
      interaction filter is particularly useful for improving predictions of
      posttranslational modifications such as phosphorylation and proteolytic cleavage
      sites. CONCLUSIONS: Genetic interaction data sets can be used to reduce false
      positive minimotif predictions. Minimotif prediction in known genetic
      interactions can help to refine the mechanisms behind the functional connection
      between genes revealed by genetic experimentation and screens.

PMID- 22403688
TI  - Wolbachia infection decreased the resistance of Drosophila to lead.
AB  - BACKGROUND: The heavy metal lead has been shown to be associated with a genotoxic
      risk. Drosophila melanogaster is a model organism commonly utilized in genetic
      toxicology testing. The endosymbionts--Wolbachia are now very common in both wild
      populations and laboratory stocks of Drosophila. Wolbachia may induce resistance
      to pathogenic viruses, filarial nematodes and Plasmodium in fruit fly and
      mosquito hosts. However the effect of Wolbachia infection on the resistance of
      their hosts to heavy metal is unknown. METHODOLOGY/PRINCIPAL FINDINGS:
      Manipulating the lead content in the diet of Drosophila melanogaster, we found
      that lead consumption had no different effects on developmental time between
      Wolbachia-infected (Dmel wMel) and -uninfected (Dmel T) flies. While in Pb
      contaminated medium, significantly reduced amount of pupae and adults of Dmel
      wMel were emerged, and Dmel wMel adults had significantly shorter longevity than
      that of Dmel T flies. Lead infusion in diet resulted in significantly decreased
      superoxide dismutase (SOD) activity in Dmel T flies (P<0.05), but not in Dmel
      wMel flies. Correspondingly, lead cultures induced a 10.8 fold increase in
      malonaldehyde (MDA) contents in Dmel T larvae (P<0.05). While in Dmel wMel
      larvae, it resulted in only a 1.3 fold increase. By quantitative RT-PCR, we
      showed that lead infused medium caused significantly increased expression level
      of relish and CecA2 genes in Dmel T flies (P<0.01). Lead cultures did not change
      dramatically the expression of these genes in Dmel wMel flies.
      CONCLUSIONS/SIGNIFICANCE: These results suggest that Wolbachia infection
      decreased the resistance of Drosophila to lead likely by limiting the production
      of peroxides resulted from lead, thus being unable to activate the immunological
      pathway in the host to prevent them from lead damage. This represents a novel
      Wolbachia-host interaction and provides information that researchers working on
      Drosophila toxicology should take in consideration the presence of Wolbachia in
      the stocks they are analyzing.

PMID- 22403689
TI  - Quantum dots do not affect the behaviour of mouse embryonic stem cells and kidney
      stem cells and are suitable for short-term tracking.
AB  - Quantum dots (QDs) are small nanocrystals widely used for labelling cells in
      order to enable cell tracking in complex environments in vitro, ex vivo and in
      vivo. They present many advantages over traditional fluorescent markers as they
      are resistant to photobleaching and have narrow emission spectra. Although QDs
      have been used effectively in cell tracking applications, their suitability has
      been questioned by reports showing they can affect stem cell behaviour and can be
      transferred to neighbouring cells. Using a variety of cellular and molecular
      biology techniques, we have investigated the effect of QDs on the proliferation
      and differentiation potential of two stem cell types: mouse embryonic stem cells
      and tissue-specific stem cells derived from mouse kidney. We have also tested if
      QDs released from living or dead cells can be taken up by neighbouring cells, and
      we have determined if QDs affect the degree of cell-cell fusion; this information
      is critical in order to assess the suitability of QDs for stem cell tracking. We
      show here that QDs have no effect on the viability, proliferation or
      differentiation potential of the two stem cell types. Furthermore, we show that
      the extent of transfer of QDs to neighbouring cells is <4%, and that QDs do not
      increase the degree of cell-cell fusion. However, although the QDs have a high
      labelling efficiency (>85%), they are rapidly depleted from both stem cell
      populations. Taken together, our results suggest that QDs are effective cell
      labelling probes that are suitable for short-term stem cell tracking.

PMID- 22403690
TI  - Recruitment potential of a green alga Ulva flexuosa Wulfen dark preserved
      zoospore and its development.
AB  - The recruitment potential and the ability of Ulva flexuosa Wulfen zoospores to
      survive darkness were tested under different conditions in the present study. The
      dark preserved zoospore was cultured under a two-factor experimental design to
      test the effect of salinity and nitrate, effect of salinity and phosphate, effect
      of light and salinity, and effect of light and phosphate. The recruitment
      (germination and growth) of zoospores was significantly affected by light and
      salinity. The nitrate concentration of 20 umol.l(-1) was found to initiate the
      process of germination and its subsequent growth and, its effect appeared
      greatest under 25 psu condition. While nitrate enhances the growth of biomass
      more than phosphate, both show a positive interactive effect on biomass increase
      when crossed with salinity. The combined effect of 25 psu salinity and 8 umol.l(
      1) phosphate exhibited higher biomass growth. There was a significant effect of
      light and salinity on the biomass of zoospore, though there was no significant
      interaction between the two factors. There was an increase in biomass of growing
      zoospores to increase in light intensity and 80 umol.m(-2).s(-1) of light
      intensity was considered optimal. Similarly, high light intensity condition
      favored higher biomass growth and there was significant interaction between light
      (80 umol. m(-2). s(-1)) and phosphate (4 umol. l(-1)) in high salinity (35 psu)
      condition. The result of this study showed that dark preserved zoospores of U.
      flexuosa have the potential for recruitment and it gives us an understanding how
      different factors play a role in the process of recruitment.

PMID- 22403691
TI  - Caveolae, fenestrae and transendothelial channels retain PV1 on the surface of
      endothelial cells.
AB  - PV1 protein is an essential component of stomatal and fenestral diaphragms, which
      are formed at the plasma membrane of endothelial cells (ECs), on structures such
      as caveolae, fenestrae and transendothelial channels. Knockout of PV1 in mice
      results in in utero and perinatal mortality. To be able to interpret the complex
      PV1 knockout phenotype, it is critical to determine whether the formation of
      diaphragms is the only cellular role of PV1. We addressed this question by
      measuring the effect of complete and partial removal of structures capable of
      forming diaphragms on PV1 protein level. Removal of caveolae in mice by knocking
      out caveolin-1 or cavin-1 resulted in a dramatic reduction of PV1 protein level
      in lungs but not kidneys. The magnitude of PV1 reduction correlated with the
      abundance of structures capable of forming diaphragms in the microvasculature of
      these organs. The absence of caveolae in the lung ECs did not affect the
      transcription or translation of PV1, but it caused a sharp increase in PV1
      protein internalization rate via a clathrin- and dynamin-independent pathway
      followed by degradation in lysosomes. Thus, PV1 is retained on the cell surface
      of ECs by structures capable of forming diaphragms, but undergoes rapid
      internalization and degradation in the absence of these structures, suggesting
      that formation of diaphragms is the only role of PV1.

PMID- 22403692
TI  - QServer: a biclustering server for prediction and assessment of co-expressed gene
      clusters.
AB  - BACKGROUND: Biclustering is a powerful technique for identification of co
      expressed gene groups under any (unspecified) substantial subset of given
      experimental conditions, which can be used for elucidation of transcriptionally
      co-regulated genes. RESULTS: We have previously developed a biclustering
      algorithm, QUBIC, which can solve more general biclustering problems than
      previous biclustering algorithms. To fully utilize the analysis power the
      algorithm provides, we have developed a web server, QServer, for prediction,
      computational validation and analyses of co-expressed gene clusters.
      Specifically, the QServer has the following capabilities in addition to
      biclustering by QUBIC: (i) prediction and assessment of conserved cis regulatory
      motifs in promoter sequences of the predicted co-expressed genes; (ii) functional
      enrichment analyses of the predicted co-expressed gene clusters using Gene
      Ontology (GO) terms, and (iii) visualization capabilities in support of
      interactive biclustering analyses. QServer supports the biclustering and
      functional analysis for a wide range of organisms, including human, mouse,
      Arabidopsis, bacteria and archaea, whose underlying genome database will be
      continuously updated. CONCLUSION: We believe that QServer provides an easy-to-use
      and highly effective platform useful for hypothesis formulation and testing
      related to transcription co-regulation.

PMID- 22403693
TI  - Identifying trustworthy experts: how do policymakers find and assess public
      health researchers worth consulting or collaborating with?
AB  - This paper reports data from semi-structured interviews on how 26 Australian
      civil servants, ministers and ministerial advisors find and evaluate researchers
      with whom they wish to consult or collaborate. Policymakers valued researchers
      who had credibility across the three attributes seen as contributing to
      trustworthiness: competence (an exemplary academic reputation complemented by
      pragmatism, understanding of government processes, and effective collaboration
      and communication skills); integrity (independence, "authenticity", and faithful
      reporting of research); and benevolence (commitment to the policy reform agenda).
      The emphases given to these assessment criteria appeared to be shaped in part by
      policymakers' roles and the type and phase of policy development in which they
      were engaged. Policymakers are encouraged to reassess their methods for engaging
      researchers and to maximise information flow and support in these relationships.
      Researchers who wish to influence policy are advised to develop relationships
      across the policy community, but also to engage in other complementary strategies
      for promoting research-informed policy, including the strategic use of mass
      media.

PMID- 22403694
TI  - Charting the NF-kappaB pathway interactome map.
AB  - Inflammation is part of a complex physiological response to harmful stimuli and
      pathogenic stress. The five components of the Nuclear Factor kappaB (NF-kappaB)
      family are prominent mediators of inflammation, acting as key transcriptional
      regulators of hundreds of genes. Several signaling pathways activated by diverse
      stimuli converge on NF-kappaB activation, resulting in a regulatory system
      characterized by high complexity. It is increasingly recognized that the number
      of components that impinges upon phenotypic outcomes of signal transduction
      pathways may be higher than those taken into consideration from canonical pathway
      representations. Scope of the present analysis is to provide a wider, systemic
      picture of the NF-kappaB signaling system. Data from different sources such as
      literature, functional enrichment web resources, protein-protein interaction and
      pathway databases have been gathered, curated, integrated and analyzed in order
      to reconstruct a single, comprehensive picture of the proteins that interact
      with, and participate to the NF-kappaB activation system. Such a reconstruction
      shows that the NF-kappaB interactome is substantially different in quantity and
      quality of components with respect to canonical representations. The analysis
      highlights that several neglected but topologically central proteins may play a
      role in the activation of NF-kappaB mediated responses. Moreover the interactome
      structure fits with the characteristics of a bow tie architecture. This
      interactome is intended as an open network resource available for further
      development, refinement and analysis.

PMID- 22403695
TI  - Effectiveness of YouRAction, an intervention to promote adolescent physical
      activity using personal and environmental feedback: a cluster RCT.
AB  - BACKGROUND: In this study the one and six months effects of the computer-tailored
      YouRAction (targeting individual level determinants) and YouRAction+e (targeting
      in addition perceived environmental determinants) on compliance with the moderate
      to-vigorous physical activity (MVPA) guideline and weight status are examined. In
      addition the use and appreciation of both interventions are studied. METHODS: A
      three-armed cluster randomized trial was conducted in 2009-2010 with measurements
      at baseline, one and six months post intervention. School classes were assigned
      to one of the study arms (YouRaction, YouRAction+e and Generic Information (GI)
      control group). MVPA was derived from self-reports at baseline, one and six
      months post intervention. Body Mass Index and waist circumference were measured
      at baseline and six months post intervention in a random sub-sample of the
      population. Use of the interventions was measured by webserver logs and
      appreciation by self-reports. Multilevel regression analyses were conducted to
      study the effects of the intervention against the GI control group. ANOVA's and
      chi-square tests were used to describe differences in use and appreciation
      between study arms. RESULTS: There were no statistically significant intervention
      effects on compliance with the MVPA guideline, overweight or WC. Access to the
      full intervention was significantly lower for YouRAction (24.0%) and YouRAction+e
      (21.7%) compared to the GI (54.4%). CONCLUSION: This study could not demonstrate
      that the YouRAction and YouRAction+e interventions were effective in promoting
      MVPA or improve anthropometric outcomes among adolescents, compared to generic
      information. Insufficient use and exposure to the intervention content may be an
      explanation for the lack of effects. TRIAL REGISTRATION: TrialRegister.nl
      NTR1923.

PMID- 22403696
TI  - Catheter related bloodstream infection (CR-BSI) in ICU patients: making the
      decision to remove or not to remove the central venous catheter.
AB  - BACKGROUND: Approximately 150 million central venous catheters (CVC) are used
      each year in the United States. Catheter-related bloodstream infections (CR-BSI)
      are one of the most important complications of the central venous catheters
      (CVCs). Our objective was to compare the in-hospital mortality when the catheter
      is removed or not removed in patients with CR-BSI. METHODS: We reviewed all
      episodes of CR-BSI that occurred in our intensive care unit (ICU) from January
      2000 to December 2008. The standard method was defined as a patient with a CVC
      and at least one positive blood culture obtained from a peripheral vein and a
      positive semi quantitative (>15 CFU) culture of a catheter segment from where the
      same organism was isolated. The conservative method was defined as a patient with
      a CVC and at least one positive blood culture obtained from a peripheral vein and
      one of the following: (1) differential time period of CVC culture versus
      peripheral culture positivity of more than 2 hours, or (2) simultaneous
      quantitative blood culture with >= 5:1 ratio (CVC versus peripheral). RESULTS: 53
      CR-BSI (37 diagnosed by the standard method and 16 by the conservative method)
      were diagnosed during the study period. There was a no statistically significant
      difference in the in-hospital mortality for the standard versus the conservative
      method (57% vs. 75%, p = 0.208) in ICU patients. CONCLUSION: In our study there
      was a no statistically significant difference between the standard and
      conservative methods in-hospital mortality.

PMID- 22403697
TI  - The rnb gene of Synechocystis PCC6803 encodes a RNA hydrolase displaying RNase II
      and not RNase R enzymatic properties.
AB  - Cyanobacteria are photosynthetic prokaryotic organisms that share characteristics
      with bacteria and chloroplasts regarding mRNA degradation. Synechocystis sp.
      PCC6803 is a model organism for cyanobacteria, but not much is known about the
      mechanism of RNA degradation. Only one member of the RNase II-family is present
      in the genome of Synechocystis sp PCC6803. This protein was shown to be essential
      for its viability, which indicates that it may have a crucial role in the
      metabolism of Synechocystis RNA. The aim of this work was to characterize the
      activity of the RNase II/R homologue present in Synechocystis sp. PCC6803. The
      results showed that as expected, it displayed hydrolytic activity and released
      nucleoside monophosphates. When compared to two E. coli counterparts, the
      activity assays showed that the Synechocystis protein displays RNase II, and not
      RNase R characteristics. This is the first reported case where when only one
      member of the RNase II/R family exists it displays RNase II and not RNase R
      characteristics.

PMID- 22403698
TI  - Prehospital electronic patient care report systems: early experiences from
      emergency medical services agency leaders.
AB  - BACKGROUND: As the United States embraces electronic health records (EHRs),
      improved emergency medical services (EMS) information systems are also a
      priority; however, little is known about the experiences of EMS agencies as they
      adopt and implement electronic patient care report (e-PCR) systems. We sought to
      characterize motivations for adoption of e-PCR systems, challenges associated
      with adoption and implementation, and emerging implementation strategies.
      METHODS: We conducted a qualitative study using semi-structured in-depth
      interviews with EMS agency leaders. Participants were recruited through a web
      based survey of National Association of EMS Physicians (NAEMSP) members, a
      didactic session at the 2010 NAEMSP Annual Meeting, and snowball sampling.
      Interviews lasted approximately 30 minutes, were recorded and professionally
      transcribed. Analysis was conducted by a five-person team, employing the constant
      comparative method to identify recurrent themes. RESULTS: Twenty-three
      interviewees represented 20 EMS agencies from the United States and Canada; 14
      EMS agencies were currently using e-PCR systems. The primary reason for adoption
      was the potential for e-PCR systems to support quality assurance efforts.
      Challenges to e-PCR system adoption included those common to any health
      information technology project, as well as challenges unique to the prehospital
      setting, including: fear of increased ambulance run times leading to decreased
      ambulance availability, difficulty integrating with existing hospital information
      systems, and unfunded mandates requiring adoption of e-PCR systems. Three
      recurring strategies emerged to improve e-PCR system adoption and implementation:
      1) identify creative funding sources; 2) leverage regional health information
      organizations; and 3) build internal information technology capacity. CONCLUSION:
      EMS agencies are highly motivated to adopt e-PCR systems to support quality
      assurance efforts; however, adoption and implementation of e-PCR systems has been
      challenging for many. Emerging strategies from EMS agencies and others that have
      successfully implemented EHRs may be useful in expanding e-PCR system use and
      facilitating this transition for other EMS agencies.

PMID- 22403699
TI  - Strengths and weaknesses of immunotherapy for advanced non-small-cell lung
      cancer: a meta-analysis of 12 randomized controlled trials.
AB  - BACKGROUND: Lung cancer is one of the leading causes of cancer death worldwide.
      Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung
      cancers. Immunotherapy has yielded no consistent benefit to date for those
      patients. Assessing the objective efficacy and safety of immunotherapy for
      advanced NSCLC patients will help to instruct the future development of
      immunotherapeutic drugs. METHODOLOGY AND PRINCIPAL FINDINGS: We performed a meta
      analysis of 12 randomized controlled trials including 3134 patients (1570
      patients in the immunotherapy group and 1564 patients in the control group) with
      histologically confirmed stage IIIA, IIIB, or IV NSCLC. The analysis was executed
      with efficacy end points regarding overall survival (OS), progression-free
      survival (PFS), complete response (CR), partial response (PR), and total
      effective rate. Overall unstratified OS, PFS, PR, and total effective rate were
      significantly improved in advanced NSCLC patients in the immunotherapy group (P =
      0.0007, 0.0004, 0.002, 0.003, respectively), whereas CR was not improved (P =
      0.97). Subgroup analysis showed that monoclonal antibody (mAb) immunotherapy
      significantly improved the PFS, PR, and total effective rate and showed a trend
      of improving OS of advanced NSCLC patients compared with the control group, with
      one kind of adverse event being significantly dominant. Compared with the control
      group, the vaccine subgroup showed no significant difference with regard to
      serious adverse events, whereas cytokine immunotherapy significantly induced
      three kinds of serious adverse events. CONCLUSIONS: Immunotherapy works
      efficiently on advanced NSCLC patients. Of several immunotherapies, mAb therapy
      may be a potential immunotherapy for advanced NSCLC patients, and become a
      standard complementary therapeutic approach in the future if the issues
      concerning toxicity and allergenicity of mAbs have been overcome.

PMID- 22403700
TI  - ArgR of Streptomyces coelicolor is a versatile regulator.
AB  - ArgR is the regulator of arginine biosynthesis genes in Streptomyces species.
      Transcriptomic comparison by microarrays has been made between Streptomyces
      coelicolor M145 and its mutant S. coelicolor DeltaargR under control,
      unsupplemented conditions, and in the presence of arginine. Expression of 459
      genes was different in transcriptomic assays, but only 27 genes were affected by
      arginine supplementation. Arginine and pyrimidine biosynthesis genes were
      derepressed by the lack of ArgR, while no strong effect on expression resulted on
      arginine supplementation. Several nitrogen metabolism genes expression as glnK,
      glnA and glnII, were downregulated in S. coelicolor DeltaargR. In addition,
      downregulation of genes for the yellow type I polyketide CPK antibiotic and for
      the antibiotic regulatory genes afsS and scbR was observed. The transcriptomic
      data were validated by either reverse transcription-PCR, expression of the gene
      promoter coupled to the luciferase gene, proteomic or by electrophoresis mobility
      shift assay (EMSA) using pure Strep-tagged ArgR. Two ARG-boxes in the arginine
      operon genes suggest that these genes are more tightly controlled. Other genes,
      including genes encoding regulatory proteins, possess a DNA sequence formed by a
      single ARG-box which responds to ArgR, as validated by EMSA.

PMID- 22403701
TI  - Preferences for very low and very high voice pitch in humans.
AB  - Manipulations of voice pitch have been shown to alter attractiveness ratings, but
      whether preferences extend to very low or very high voice pitch is unknown. Here,
      we manipulated voice pitch in averaged men's and women's voices by 2 Hz intervals
      to create a range of male and female voices speaking monopthong vowel sounds and
      spanning a range of frequencies from normal to very low and very high pitch. With
      these voices, we used the method of constant stimuli to measure preferences for
      voice. Nineteen university students (ages: 20-25) participated in three
      experiments. On average, men preferred high-pitched women's voices to low-pitched
      women's voices across all frequencies tested. On average, women preferred men's
      voices lowered in pitch, but did not prefer very low men's voices. The results of
      this study may reflect selection pressures for men's and women's voices, and shed
      light on a perceptual link between voice pitch and vocal attractiveness.

PMID- 22403702
TI  - Interplay of filaggrin loss-of-function variants, allergic sensitization, and
      eczema in a longitudinal study covering infancy to 18 years of age.
AB  - BACKGROUND: Immune specific genes as well as genes regulating the formation of
      skin barrier are major determinants for eczema manifestation. There is a debate
      as to whether allergic sensitization and filaggrin gene (FLG) variants lead to
      eczema or FLG variants and eczema increase the risk of allergic sensitization. To
      investigate the time-order between eczema and allergic sensitization with respect
      to FLG variants, data from a large prospective study covering infancy to late
      adolescence were analyzed. METHODOLOGY/PRINCIPAL FINDINGS: Repeated measurements
      of eczema and allergic sensitization (documented by skin prick tests) at ages 1,
      2, 4, 10, and 18 years were ascertained in the Isle of Wight birth cohort (n =
      1,456). Three transition periods were analyzed: age 1-or-2 to 4, 4 to 10, and 10
      to 18 years. FLG variants were genotyped in 1,150 participants. Over the three
      transition periods, in temporal sequence analyses of initially eczema-free
      participants, the combined effect of FLG variants and allergic sensitization
      showed a 2.92-fold (95% CI: 1.47-5.77) increased risk ratio (RR) of eczema in
      subsequent examinations. This overall risk was more pronounced at a younger age
      (transition period 1-or-2 to 4, RR = 6.47, 95% CI: 1.96-21.33). In contrast, FLG
      variants in combination with eczema showed a weaker, but significant, risk ratio
      for subsequent allergic sensitization only up to 10 years of age.
      CONCLUSIONS/SIGNIFICANCE: Taking the time order into account, this prospective
      study demonstrates for the first time, that a combination of FLG variants and
      allergic sensitization increased the risk of eczema in subsequent years. Also FLG
      variants interacted with eczema and increased the risk of subsequent allergic
      sensitization, which, was limited to the younger age. Hence, early restoration of
      defective skin barrier could prevent allergic sensitization and subsequently
      reduce the risk of eczema development.

PMID- 22403703
TI  - Optimization of time-course experiments for kinetic model discrimination.
AB  - Systems biology relies heavily on the construction of quantitative models of
      biochemical networks. These models must have predictive power to help unveiling
      the underlying molecular mechanisms of cellular physiology, but it is also
      paramount that they are consistent with the data resulting from key experiments.
      Often, it is possible to find several models that describe the data equally well,
      but provide significantly different quantitative predictions regarding particular
      variables of the network. In those cases, one is faced with a problem of model
      discrimination, the procedure of rejecting inappropriate models from a set of
      candidates in order to elect one as the best model to use for prediction.In this
      work, a method is proposed to optimize the design of enzyme kinetic assays with
      the goal of selecting a model among a set of candidates. We focus on models with
      systems of ordinary differential equations as the underlying mathematical
      description. The method provides a design where an extension of the Kullback
      Leibler distance, computed over the time courses predicted by the models, is
      maximized. Given the asymmetric nature this measure, a generalized differential
      evolution algorithm for multi-objective optimization problems was used.The
      kinetics of yeast glyoxalase I (EC 4.4.1.5) was chosen as a difficult test case
      to evaluate the method. Although a single-substrate kinetic model is usually
      considered, a two-substrate mechanism has also been proposed for this enzyme. We
      designed an experiment capable of discriminating between the two models by
      optimizing the initial substrate concentrations of glyoxalase I, in the presence
      of the subsequent pathway enzyme, glyoxalase II (EC 3.1.2.6). This discriminatory
      experiment was conducted in the laboratory and the results indicate a two
      substrate mechanism for the kinetics of yeast glyoxalase I.

PMID- 22403704
TI  - Endocrine disruptor regulation of microRNA expression in breast carcinoma cells.
AB  - BACKGROUND: Several environmental agents termed "endocrine disrupting compounds"
      or EDCs have been reported to bind and activate the estrogen receptor-alpha (ER).
      The EDCs DDT and BPA are ubiquitously present in the environment, and DDT and BPA
      levels in human blood and adipose tissue are detectable in most if not all women
      and men. ER-mediated biological responses can be regulated at numerous levels,
      including expression of coding RNAs (mRNAs) and more recently non-coding RNAs
      (ncRNAs). Of the ncRNAs, microRNAs have emerged as a target of estrogen
      signaling. Given the important implications of EDC-regulated ER function, we
      sought to define the effects of BPA and DDT on microRNA regulation and expression
      levels in estrogen-responsive human breast cancer cells. METHODOLOGY/PRINCIPAL
      FINDINGS: To investigate the cellular effects of DDT and BPA, we used the human
      MCF-7 breast cancer cell line, which is ER (+) and hormone sensitive. Our results
      show that DDT and BPA potentiate ER transcriptional activity, resulting in an
      increased expression of receptor target genes, including progesterone receptor,
      bcl-2, and trefoil factor 1. Interestingly, a differential increase in expression
      of Jun and Fas by BPA but not DDT or estrogen was observed. In addition to ER
      responsive mRNAs, we investigated the ability of DDT and BPA to alter the miRNA
      profiles in MCF-7 cells. While the EDCs and estrogen similarly altered the
      expression of multiple microRNAs in MCF-7 cells, including miR-21, differential
      patterns of microRNA expression were induced by DDT and BPA compared to estrogen.
      CONCLUSIONS/SIGNIFICANCE: We have shown, for the first time, that BPA and DDT,
      two well known EDCs, alter the expression profiles of microRNA in MCF-7 breast
      cancer cells. A better understanding of the molecular mechanisms of these
      compounds could provide important insight into the role of EDCs in human disease,
      including breast cancer.

PMID- 22403705
TI  - Modification of EGF-like module 1 of thrombospondin-1, an animal extracellular
      protein, by O-linked N-acetylglucosamine.
AB  - Thrombospondin-1 (TSP-1) is known to be subject to three unusual carbohydrate
      modifications: C-mannosylation, O-fucosylation, and O-glucosylation. We now
      describe a fourth: O-beta-N-acetylglucosaminylation. Previously, O-beta-N
      acetylglucosamine (O-beta-GlcNAc) was found on a threonine in the loop between
      the fifth and sixth cysteines of the 20(th) epidermal growth factor (EGF)-like
      module of Drosophila Notch. A BLAST search based on the Drosophila Notch loop
      sequence identified a number of human EGF-like modules that contain a similar
      sequence, including EGF-like module 1 of TSP-1 and its homolog, TSP-2. TSP-1,
      which has a potentially modifiable serine in the loop, reacted in immuno-blots
      with the CTD110.6 anti-O-GlcNAc antibody. Antibody reactivity was diminished by
      treatment of TSP-1 with beta-N-acetylhexosaminidase. TSP-2, which lacks a
      potentially modifiable serine/threonine in the loop, did not react with CTD110.6.
      Analysis of tandem modules of TSP-1 localized reactivity of CTD110.6 to EGF-like
      module 1. Top-down mass spectrometric analysis of EGF-like module 1 demonstrated
      the expected modifications with glucose (+162 Da) and xylose (+132 Da) separately
      from modification with N-acetyl hexosamine (+203 Da). Mass spectrometric sequence
      analysis localized the +203-Da modification to Ser580 in the sequence
      (575)CPPGYSGNGIQC(586). These results demonstrate that O-beta-N
      acetylglucosaminylation can occur on secreted extracellular matrix proteins as
      well as on cell surface proteins.

PMID- 22403706
TI  - Predicting the effect of surface texture on the qualitative form of prehension.
AB  - Reach-to-grasp movements change quantitatively in a lawful (i.e. predictable)
      manner with changes in object properties. We explored whether altering object
      texture would produce qualitative changes in the form of the precontact movement
      patterns. Twelve participants reached to lift objects from a tabletop. Nine
      objects were produced, each with one of three grip surface textures (high
      friction, medium-friction and low-friction) and one of three widths (50 mm, 70 mm
      and 90 mm). Each object was placed at three distances (100 mm, 300 mm and 500
      mm), representing a total of 27 trial conditions. We observed two distinct
      movement patterns across all trials--participants either: (i) brought their arm
      to a stop, secured the object and lifted it from the tabletop; or (ii) grasped
      the object 'on-the-fly', so it was secured in the hand while the arm was moving.
      A majority of grasps were on-the-fly when the texture was high-friction and none
      when the object was low-friction, with medium-friction producing an intermediate
      proportion. Previous research has shown that the probability of on-the-fly
      behaviour is a function of grasp surface accuracy constraints. A finger friction
      rig was used to calculate the coefficients of friction for the objects and these
      calculations showed that the area available for a stable grasp (the 'functional
      grasp surface size') increased with surface friction coefficient. Thus, knowledge
      of functional grasp surface size is required to predict the probability of
      observing a given qualitative form of grasping in human prehensile behaviour.

PMID- 22403707
TI  - Benefits for dominant red deer hinds under a competitive feeding system: food
      access behavior, diet and nutrient selection.
AB  - Social dominance is widely known to facilitate access to food resources in many
      animal species such as deer. However, research has paid little attention to
      dominance in ad libitum access to food because it was thought not to result in
      any benefit for dominant individuals. In this study we assessed if, even under ad
      libitum conditions, social rank may allow dominant hinds to consume the preferred
      components of food. Forty-four red deer hinds (Cervus elaphus) were allowed to
      consume ad libitum meal consisting of pellets of sunflower, lucerne and orange,
      and seeds of cereals, corn, cotton, and carob tree. The meal was placed only in
      one feeder, which reduced accessibility to a few individuals simultaneously.
      During seven days, feeding behavior (order of access, time to first feeding bout,
      total time spent feeding, and time per feeding bout) were assessed during the
      first hour. The relative abundance of each meal component was assessed at times
      0, 1 and 5 h, as well as its nutritional composition. Social rank was positively
      related to the amount of time spent feeding during the 1(st) h (P = 0.048).
      Selection indices were positively correlated with energy (P = 0.018 during the
      1(st) h and P = 0.047 from 1(st) to 5(th)) and fat (only during the 1(st) h; P =
      0.036), but also negatively with certain minerals. Thus, dominant hinds could
      select high energy meal components for longer time under an ad libitum but
      restricted food access setting. Selection indices showed a higher selectivity
      when food availability was higher (1(st) hour respect to 1(st) to 5(th)).
      Finally, high and low ranking hinds had longer time per feeding bout than mid
      ones (P = 0.011), suggesting complex behavioral feeding tactics of low ranking
      social ungulates.

PMID- 22403708
TI  - Synthesis of a dual functional anti-MDR tumor agent PH II-7 with elucidations of
      anti-tumor effects and mechanisms.
AB  - Multidrug resistance mediated by P-glycoprotein in cancer cells has been a major
      issue that cripples the efficacy of chemotherapy agents. Aimed for improved
      efficacy against resistant cancer cells, we designed and synthesized 25 oxindole
      derivatives based on indirubin by structure-activity relationship analysis. The
      most potent one was named PH II-7, which was effective against 18 cancer cell
      lines and 5 resistant cell lines in MTT assay. It also significantly inhibited
      the resistant xenograft tumor growth in mouse model. In cell cycle assay and
      apoptosis assay conducted with flow cytometry, PH II-7 induced S phase cell cycle
      arrest and apoptosis even in resistant cells. Consistently revealed by real-time
      PCR, it modulates the expression of genes related to the cell cycle and apoptosis
      in these cells, which may contributes to its efficacy against them. By side-chain
      modification and FITC-labeling of PH II-7, we were able to show with confocal
      microscopy that not only it was not pumped by P-glycoprotein, it also attenuated
      the efflux of Adriamycin by P-glycoprotein in MDR tumor cells. Real-time PCR and
      western blot analysis showed that PH II-7 down-regulated MDR1 gene via protein
      kinase C alpha (PKCA) pathway, with c-FOS and c-JUN as possible mediators. Taken
      together, PH II-7 is a dual-functional compound that features both the
      cytotoxicity against cancer cells and the inhibitory effect on P-gp mediated drug
      efflux.

PMID- 22403709
TI  - Spike-interval triggered averaging reveals a quasi-periodic spiking alternative
      for stochastic resonance in catfish electroreceptors.
AB  - Catfish detect and identify invisible prey by sensing their ultra-weak electric
      fields with electroreceptors. Any neuron that deals with small-amplitude input
      has to overcome sensitivity limitations arising from inherent threshold non
      linearities in spike-generation mechanisms. Many sensory cells solve this issue
      with stochastic resonance, in which a moderate amount of intrinsic noise causes
      irregular spontaneous spiking activity with a probability that is modulated by
      the input signal. Here we show that catfish electroreceptors have adopted a
      fundamentally different strategy. Using a reverse correlation technique in which
      we take spike interval durations into account, we show that the electroreceptors
      generate a supra-threshold bias current that results in quasi-periodically
      produced spikes. In this regime stimuli modulate the interval between successive
      spikes rather than the instantaneous probability for a spike. This alternative
      for stochastic resonance combines threshold-free sensitivity for weak stimuli
      with similar sensitivity for excitations and inhibitions based on single
      interspike intervals.

PMID- 22403710
TI  - Mechanisms underlying insulin deficiency-induced acceleration of beta-amyloidosis
      in a mouse model of Alzheimer's disease.
AB  - Although evidence is accumulating that diabetes mellitus is an important risk
      factor for sporadic Alzheimer's disease (AD), the mechanisms by which defects in
      insulin signaling may lead to the acceleration of AD progression remain unclear.
      In this study, we applied streptozotocin (STZ) to induce experimental diabetes in
      AD transgenic mice (5XFAD model) and investigated how insulin deficiency affects
      the beta-amyloidogenic processing of amyloid precursor protein (APP). Two and
      half months after 5XFAD mice were treated with STZ (90 mg/kg, i.p., once daily
      for two consecutive days), they showed significant reductions in brain insulin
      levels without changes in insulin receptor expression. Concentrations of cerebral
      amyloid-beta peptides (Abeta40 and Abeta42) were significantly increased in STZ
      treated 5XFAD mice as compared with vehicle-treated 5XFAD controls. Importantly,
      STZ-induced insulin deficiency upregulated levels of both beta-site APP cleaving
      enzyme 1 (BACE1) and full-length APP in 5XFAD mouse brains, which was accompanied
      by dramatic elevations in the beta-cleaved C-terminal fragment (C99).
      Interestingly, BACE1 mRNA levels were not affected, whereas phosphorylation of
      the translation initiation factor eIF2alpha, a mechanism proposed to mediate the
      post-transcriptional upregulation of BACE1, was significantly elevated in STZ
      treated 5XFAD mice. Meanwhile, levels of GGA3, an adapter protein responsible for
      sorting BACE1 to lysosomal degradation, are indistinguishable between STZ- and
      vehicle-treated 5XFAD mice. Moreover, STZ treatments did not affect levels of
      Abeta-degrading enzymes such as neprilysin and insulin-degrading enzyme (IDE) in
      5XFAD brains. Taken together, our findings provide a mechanistic foundation for a
      link between diabetes and AD by demonstrating that insulin deficiency may change
      APP processing to favor beta-amyloidogenesis via the translational upregulation
      of BACE1 in combination with elevations in its substrate, APP.

PMID- 22403711
TI  - Cell-type specific roles for PTEN in establishing a functional retinal
      architecture.
AB  - BACKGROUND: The retina has a unique three-dimensional architecture, the precise
      organization of which allows for complete sampling of the visual field. Along the
      radial or apicobasal axis, retinal neurons and their dendritic and axonal arbors
      are segregated into layers, while perpendicular to this axis, in the tangential
      plane, four of the six neuronal types form patterned cellular arrays, or mosaics.
      Currently, the molecular cues that control retinal cell positioning are not well
      understood, especially those that operate in the tangential plane. Here we
      investigated the role of the PTEN phosphatase in establishing a functional
      retinal architecture. METHODOLOGY/PRINCIPAL FINDINGS: In the developing retina,
      PTEN was localized preferentially to ganglion, amacrine and horizontal cells,
      whose somata are distributed in mosaic patterns in the tangential plane.
      Generation of a retina-specific Pten knock-out resulted in retinal ganglion,
      amacrine and horizontal cell hypertrophy, and expansion of the inner plexiform
      layer. The spacing of Pten mutant mosaic populations was also aberrant, as were
      the arborization and fasciculation patterns of their processes, displaying cell
      type-specific defects in the radial and tangential dimensions. Irregular
      oscillatory potentials were also observed in Pten mutant electroretinograms,
      indicative of asynchronous amacrine cell firing. Furthermore, while Pten mutant
      RGC axons targeted appropriate brain regions, optokinetic spatial acuity was
      reduced in Pten mutant animals. Finally, while some features of the Pten mutant
      retina appeared similar to those reported in Dscam-mutant mice, PTEN expression
      and activity were normal in the absence of Dscam. CONCLUSIONS/SIGNIFICANCE: We
      conclude that Pten regulates somal positioning and neurite arborization patterns
      of a subset of retinal cells that form mosaics, likely functioning independently
      of Dscam, at least during the embryonic period. Our findings thus reveal an
      unexpected level of cellular specificity for the multi-purpose phosphatase, and
      identify Pten as an integral component of a novel cell positioning pathway in the
      retina.

PMID- 22403712
TI  - Morbillivirus glycoprotein expression induces ER stress, alters Ca2+ homeostasis
      and results in the release of vasostatin.
AB  - Although the pathology of Morbillivirus in the central nervous system (CNS) is
      well described, the molecular basis of neurodegenerative events still remains
      poorly understood. As a model to explore Morbillivirus-mediated CNS dysfunctions,
      we used canine distemper virus (CDV) that we inoculated into two different cell
      systems: a monkey cell line (Vero) and rat primary hippocampal neurons.
      Importantly, the recombinant CDV used in these studies not only efficiently
      infects both cell types but recapitulates the uncommon, non-cytolytic cell-to
      cell spread mediated by virulent CDVs in brain of dogs. Here, we demonstrated
      that both CDV surface glycoproteins (F and H) markedly accumulated in the
      endoplasmic reticulum (ER). This accumulation triggered an ER stress,
      characterized by increased expression of the ER resident chaperon calnexin and
      the proapoptotic transcription factor CHOP/GADD 153. The expression of
      calreticulin (CRT), another ER resident chaperon critically involved in the
      response to misfolded proteins and in Ca(2+) homeostasis, was also upregulated.
      Transient expression of recombinant CDV F and H surface glycoproteins in Vero
      cells and primary hippocampal neurons further confirmed a correlation between
      their accumulation in the ER, CRT upregulation, ER stress and disruption of ER
      Ca(2+) homeostasis. Furthermore, CDV infection induced CRT fragmentation with re
      localisation of a CRT amino-terminal fragment, also known as vasostatin, on the
      surface of infected and neighbouring non-infected cells. Altogether, these
      results suggest that ER stress, CRT fragmentation and re-localization on the cell
      surface may contribute to cytotoxic effects and ensuing cell dysfunctions
      triggered by Morbillivirus, a mechanism that might potentially be relevant for
      other neurotropic viruses.

PMID- 22403713
TI  - Contrasted patterns of selection on MHC-linked microsatellites in natural
      populations of the Malagasy plague reservoir.
AB  - Plague (Yersinia pestis infection) is a highly virulent rodent disease that
      persists in many natural ecosystems. The black rat (Rattus rattus) is the main
      host involved in the plague focus of the central highlands of Madagascar. Black
      rat populations from this area are highly resistant to plague, whereas those from
      areas in which the disease is absent (low altitude zones of Madagascar) are
      susceptible. Various lines of evidence suggest a role for the Major
      Histocompatibility Complex (MHC) in plague resistance. We therefore used the MHC
      region as a candidate for detecting signatures of plague-mediated selection in
      Malagasy black rats, by comparing population genetic structures for five MHC
      linked microsatellites and neutral markers in two sampling designs. We first
      compared four pairs of populations, each pair including one population from the
      plague focus and one from the disease-free zone. Plague-mediated selection was
      expected to result in greater genetic differentiation between the two zones than
      expected under neutrality and this was observed for one MHC-class I-linked locus
      (D20Img2). For this marker as well as for four other MHC-linked loci, a
      geographic pattern of genetic structure was found at local scale within the
      plague focus. This pattern would be expected if plague selection pressures were
      spatially variable. Finally, another MHC-class I-linked locus (D20Rat21) showed
      evidences of balancing selection, but it seems more likely that this selection
      would be related to unknown pathogens more widely distributed in Madagascar than
      plague.

PMID- 22403714
TI  - Ribosome distribution in HeLa cells during the cell cycle.
AB  - In this study, we employed a surface-specific antibody against the large ribosome
      subunit to investigate the distribution of ribosomes in cells during the cell
      cycle. The antibody, anti-L7n, was raised against an expansion segment (ES)
      peptide from the large subunit ribosomal protein L7, and its ribosome-surface
      specificity was evident from the positive immuno-reactivity of ribosome particles
      and the detection of 60 S immune-complex formation by an immuno-electron
      microscopy. Using immunofluorescent staining, we have microscopically revealed
      that ribosomes are dispersed in the cytoplasm of cells throughout all phases of
      the cell cycle, except at the G2 phase where ribosomes show a tendency to gather
      toward the nuclear envelope. The finding in G2 cells was confirmed by electron
      microscopy using a morphometric assay and paired t test. Furthermore, further
      observations have shown that ribosomes are not distributed immune-fluorescently
      with nuclear envelope markers including the nuclear pore complex, the integral
      membrane protein gp210, the inner membrane protein lamin B2, and the endoplasm
      reticulum membrane during cell division we propose that the mechanism associated
      with ribosome segregation into daughter cells could be independent of the
      processes of disassembly and reassembly of the nuclear envelope.

PMID- 22403715
TI  - Regulation of fission yeast morphogenesis by PP2A activator pta2.
AB  - Cell polarization is key for the function of most eukaryotic cells, and regulates
      cell shape, migration and tissue architecture. Fission yeast, Schizosaccharomyces
      pombe cells are cylindrical and polarize cell growth to one or both cell tips
      dependent on the cell cycle stage. Whereas microtubule cytoskeleton contributes
      to the positioning of the growth sites by delivering polarity factors to the cell
      ends, the Cdc42 GTPase polarizes secretion via actin-dependent delivery and
      tethering of secretory vesicles to plasma membrane. How growth is restricted to
      cell tips and how re-initiation of tip growth is regulated in the cell cycle
      remains poorly understood. In this work we investigated the function of protein
      phosphatase type 2A (PP2A) in S. pombe morphogenesis by deleting the evolutionary
      conserved PTPA-type regulatory subunit that we named pta2. pta2-deleted cells
      showed morphological defects and altered growth pattern. Consistent with this,
      actin patches and active Cdc42 were mislocalized in the pta2 deletion. These
      defects were additive to the lack of Cdc42-GAP Rga4. pta2Delta cells show
      upregulated Cdc42 activity and pta2 interacts genetically with polarisome
      components Tea1, Tea4 and For3 leading to complete loss of cell polarity and
      rounded morphology. Thus, regulation of polarity by PP2A requires the polarisome
      and involves Pta2-dependent control of Cdc42 activity.

PMID- 22403716
TI  - Detection of Mycobacterium tuberculosis in sputum by gas chromatography-mass
      spectrometry of methyl mycocerosates released by thermochemolysis.
AB  - Tuberculosis requires rapid diagnosis to prevent further transmission and allow
      prompt administration of treatment. Current methods for diagnosing pulmonary
      tuberculosis lack sensitivity are expensive or are extremely slow. The
      identification of lipids using gas chromatography- electron impact mass
      spectrometry (GC-EI/MS) could provide an alternative solution. We have studied
      mycocerosic acid components of the phthiocerol dimycocerosate (PDIM) family of
      lipids using thermochemolysis GC-EI/MS. To facilitate use of the technology in a
      routine diagnostic laboratory a simple extraction procedure was employed where
      PDIMs were extracted from sputum using petroleum ether, a solvent of low
      polarity. We also investigated a method using methanolic tetramethylammonium
      hydroxide, which facilitates direct transesterification of acidic components to
      methyl esters in the inlet of the GC-MS system. This eliminates conventional
      chemical manipulations allowing rapid and convenient analysis of samples. When
      applied to an initial set of 40 sputum samples, interpretable results were
      obtained for 35 samples with a sensitivity relative to culture of 94% (95%CI:
      69.2,100) and a specificity of 100% (95%CI: 78.1,100). However, blinded testing
      of a larger set of 395 sputum samples found the assay to have a sensitivity of
      61.3% (95%CI: 54.9,67.3) and a specificity of 70.6% (95%CI: 62.3,77.8) when
      compared to culture. Using the results obtained we developed an improved set of
      classification criteria, which when applied in a blinded re-analysis increased
      the sensitivity and specificity of the assay to 64.9% (95%CI: 58.6,70.8) and
      76.2% (95%CI: 68.2,82.8) respectively. Highly variable levels of background
      signal were observed from individual sputum samples that inhibited interpretation
      of the data. The diagnostic potential of using thermochemolytic GC-EI/MS of PDIM
      biomarkers for diagnosis of tuberculosis in sputum has been established; however,
      further refinements in sample processing are required to enhance the sensitivity
      and robustness of the test.

PMID- 22403717
TI  - Presumed symbolic use of diurnal raptors by Neanderthals.
AB  - In Africa and western Eurasia, occurrences of burials and utilized ocher
      fragments during the late Middle and early Late Pleistocene are often considered
      evidence for the emergence of symbolically-mediated behavior. Perhaps less
      controversial for the study of human cognitive evolution are finds of marine
      shell beads and complex designs on organic and mineral artifacts in early modern
      human (EMH) assemblages conservatively dated to ~ 100-60 kilo-years (ka) ago.
      Here we show that, in France, Neanderthals used skeletal parts of large diurnal
      raptors presumably for symbolic purposes at Combe-Grenal in a layer dated to
      marine isotope stage (MIS) 5b (~ 90 ka) and at Les Fieux in stratigraphic units
      dated to the early/middle phase of MIS 3 (60-40 ka). The presence of similar
      objects in other Middle Paleolithic contexts in France and Italy suggest that
      raptors were used as means of symbolic expression by Neanderthals in these
      regions.

PMID- 22403718
TI  - Interaction pattern of Arg 62 in the A-pocket of differentially disease
      associated HLA-B27 subtypes suggests distinct TCR binding modes.
AB  - The single amino acid replacement Asp116His distinguishes the two subtypes HLA
      B*2705 and HLA-B*2709 which are, respectively, associated and non-associated with
      Ankylosing Spondylitis, an autoimmune chronic inflammatory disease. The reason
      for this differential association is so far poorly understood and might be
      related to subtype-specific HLA:peptide conformations as well as to
      subtype/peptide-dependent dynamical properties on the nanoscale. Here, we combine
      functional experiments with extensive molecular dynamics simulations to
      investigate the molecular dynamics and function of the conserved Arg62 of the
      alpha1-helix for both B27 subtypes in complex with the self-peptides pVIPR
      (RRKWRRWHL) and TIS (RRLPIFSRL), and the viral peptides pLMP2 (RRRWRRLTV) and
      NPflu (SRYWAIRTR). Simulations of HLA:peptide systems suggest that peptide
      stabilizing interactions of the Arg62 residue observed in crystal structures are
      metastable for both B27 subtypes under physiological conditions, rendering this
      arginine solvent-exposed and, probably, a key residue for TCR interaction more
      than peptide-binding. This view is supported by functional experiments with
      conservative (R62K) and non-conservative (R62A) B*2705 and B*2709 mutants that
      showed an overall reduction in their capability to present peptides to CD8+ T
      cells. Moreover, major subtype-dependent differences in the peptide recognition
      suggest distinct TCR binding modes for the B*2705 versus the B*2709 subtype.

PMID- 22403719
TI  - Drosophila nociceptors mediate larval aversion to dry surface environments
      utilizing both the painless TRP channel and the DEG/ENaC subunit, PPK1.
AB  - A subset of sensory neurons embedded within the Drosophila larval body wall have
      been characterized as high-threshold polymodal nociceptors capable of responding
      to noxious heat and noxious mechanical stimulation. They are also sensitized by
      UV-induced tissue damage leading to both thermal hyperalgesia and allodynia very
      similar to that observed in vertebrate nociceptors. We show that the class IV
      multiple-dendritic(mdIV) nociceptors are also required for a normal larval
      aversion to locomotion on to a dry surface environment. Drosophila melanogaster
      larvae are acutely susceptible to desiccation displaying a strong aversion to
      locomotion on dry surfaces severely limiting the distance of movement away from a
      moist food source. Transgenic inactivation of mdIV nociceptor neurons resulted in
      larvae moving inappropriately into regions of low humidity at the top of the vial
      reflected as an increased overall pupation height and larval desiccation. This
      larval lethal desiccation phenotype was not observed in wild-type controls and
      was completely suppressed by growth in conditions of high humidity. Transgenic
      hyperactivation of mdIV nociceptors caused a reciprocal hypersensitivity to dry
      surfaces resulting in drastically decreased pupation height but did not induce
      the writhing nocifensive response previously associated with mdIV nociceptor
      activation by noxious heat or harsh mechanical stimuli. Larvae carrying mutations
      in either the Drosophila TRP channel, Painless, or the degenerin/epithelial
      sodium channel subunit Pickpocket1(PPK1), both expressed in mdIV nociceptors,
      showed the same inappropriate increased pupation height and lethal desiccation
      observed with mdIV nociceptor inactivation. Larval aversion to dry surfaces
      appears to utilize the same or overlapping sensory transduction pathways
      activated by noxious heat and harsh mechanical stimulation but with strikingly
      different sensitivities and disparate physiological responses.

PMID- 22403720
TI  - Entorhinal denervation induces homeostatic synaptic scaling of excitatory
      postsynapses of dentate granule cells in mouse organotypic slice cultures.
AB  - Denervation-induced changes in excitatory synaptic strength were studied
      following entorhinal deafferentation of hippocampal granule cells in mature (>= 3
      weeks old) mouse organotypic entorhino-hippocampal slice cultures. Whole-cell
      patch-clamp recordings revealed an increase in excitatory synaptic strength in
      response to denervation during the first week after denervation. By the end of
      the second week synaptic strength had returned to baseline. Because these
      adaptations occurred in response to the loss of excitatory afferents, they
      appeared to be in line with a homeostatic adjustment of excitatory synaptic
      strength. To test whether denervation-induced changes in synaptic strength
      exploit similar mechanisms as homeostatic synaptic scaling following
      pharmacological activity blockade, we treated denervated cultures at 2 days post
      lesion for 2 days with tetrodotoxin. In these cultures, the effects of
      denervation and activity blockade were not additive, suggesting that similar
      mechanisms are involved. Finally, we investigated whether entorhinal denervation,
      which removes afferents from the distal dendrites of granule cells while leaving
      the associational afferents to the proximal dendrites of granule cells intact,
      results in a global or a local up-scaling of granule cell synapses. By using
      computational modeling and local electrical stimulations in Strontium (Sr(2+))
      containing bath solution, we found evidence for a lamina-specific increase in
      excitatory synaptic strength in the denervated outer molecular layer at 3-4 days
      post lesion. Taken together, our data show that entorhinal denervation results in
      homeostatic functional changes of excitatory postsynapses of denervated dentate
      granule cells in vitro.

PMID- 22403722
TI  - Gendered risk perceptions associated with human-wildlife conflict: implications
      for participatory conservation.
AB  - This research aims to foster discourse about the extent to which gender is
      important to consider within the context of participatory approaches for
      biological conservation. Our objectives are to: (1) gender-disaggregate data
      about stakeholders' risk perceptions associated with human-wildlife conflict
      (HWC) in a participatory conservation context, and (2) highlight insights from
      characterizing gendered similarities and differences in the way people think
      about HWC-related risks. Two communal conservancies in Caprivi, Namibia served as
      case study sites. We analyzed data from focus groups (n = 2) to create gendered
      concept maps about risks to wildlife and livelihoods and any associations of
      those risks with HWC, and semi-structured interviews (n = 76; men = 38, women =
      38) to measure explicit risk attitudes associated with HWC. Concept maps
      indicated some divergent perceptions in how groups characterized risks to
      wildlife and livelihoods; however, not only were identified risks to wildlife
      (e.g., pollution, hunting) dissimilar in some instances, descriptions of risks
      varied as well. Study groups reported similar risk perceptions associated with
      HWC with the exception of worry associated with HWC effects on local livelihoods.
      Gendered differences in risk perceptions may signal different priorities or
      incentives to participate in efforts to resolve HWC-related risks. Thus, although
      shared goals and interests may seem to be an obvious reason for cooperative
      wildlife management, it is not always obvious that management goals are shared.
      Opportunity exists to move beyond thinking about gender as an explanatory
      variable for understanding how different groups think about participating in
      conservation activities.

PMID- 22403721
TI  - Targeted disruption of ephrin B1 in cells of myeloid lineage increases osteoclast
      differentiation and bone resorption in mice.
AB  - Disruption of ephrin B1 in collagen I producing cells in mice results in severe
      skull defects and reduced bone formation. Because ephrin B1 is also expressed
      during osteoclast differentiation and because little is known on the role of
      ephrin B1 reverse signaling in bone resorption, we examined the bone phenotypes
      in ephrin B1 conditional knockout mice, and studied the function of ephrin B1
      reverse signaling on osteoclast differentiation and resorptive activity. Targeted
      deletion of ephrin B1 gene in myeloid lineage cells resulted in reduced
      trabecular bone volume, trabecular number and trabecular thickness caused by
      increased TRAP positive osteoclasts and bone resorption. Histomorphometric
      analyses found bone formation parameters were not changed in ephrin B1 knockout
      mice. Treatment of wild-type precursors with clustered soluble EphB2-Fc inhibited
      RANKL induced formation of multinucleated osteoclasts, and bone resorption pits.
      The same treatment of ephrin B1 deficient precursors had little effect on
      osteoclast differentiation and pit formation. Similarly, activation of ephrin B1
      reverse signaling by EphB2-Fc treatment led to inhibition of TRAP, cathepsin K
      and NFATc1 mRNA expression in osteoclasts derived from wild-type mice but not
      conditional knockout mice. Immunoprecipitation with NHERF1 antibody revealed
      ephrin B1 interacted with NHERF1 in differentiated osteoclasts. Treatment of
      osteoclasts with exogenous EphB2-Fc resulted in reduced phosphorylation of
      ezrin/radixin/moesin. We conclude that myeloid lineage produced ephrin B1 is a
      negative regulator of bone resorption in vivo, and that activation of ephrin B1
      reverse signaling inhibits osteoclast differentiation in vitro in part via a
      mechanism that involves inhibition of NFATc1 expression and modulation of
      phosphorylation status of ezrin/radixin/moesin.

PMID- 22403723
TI  - Inverse relationship between PSA and IL-8 in prostate cancer: an insight into a
      NF-kappaB-mediated mechanism.
AB  - BACKGROUND: Prostate specific antigen (PSA) is traditionally used as an indicator
      for the presence of prostate cancer (PCa) and radiotherapy is generally used to
      treat inoperable and locally advanced PCa. However, how cellular PSA level is
      associated with sensitivity of PCa to radiotherapy is unknown. The previous
      finding that the RelB-based NF-kappaB alternative pathway differentially
      regulates PSA and interleukin-8 (IL-8) in aggressive PCa has directed our
      attention to the role of RelB in the response of PCa to radiotherapy.
      METHODOLOGY/PRINCIPAL FINDINGS: RelB and its targets PSA and IL-8 in PCa cells
      were manipulated by ectopic expression in PCa cells with a low endogenous level
      of RelB (LNCaP) and by RNAi-based knock-down in PCa cells with a high
      constitutive level of RelB (PC3). The effects of RelB, PSA and IL-8 on the
      response of PCa to radiation treatment were examined in vitro and in xenograft
      tumors. RelB regulates PSA and IL-8 in an inverse manner. When the cellular
      levels of PSA and IL-8 were directly modulated by genetic manipulations or by the
      addition of recombinant proteins, the results demonstrate that up-regulation of
      IL-8 enhanced radioresistance of PCa cells and concurrently down-regulated PSA.
      In contrast, up-regulation of PSA resulted in reduced radioresistance with
      concurrent down-regulation of IL-8. CONCLUSION/SIGNIFICANCE: RelB plays a
      critical role in the response of PCa to radiotherapy and the inverse expression
      of IL-8 and PSA. The results identify a previously unrecognized relationship
      between IL-8 and PSA in the response of PCa cells to radiotherapy.

PMID- 22403724
TI  - Multiscale feature analysis of salivary gland branching morphogenesis.
AB  - Pattern formation in developing tissues involves dynamic spatio-temporal changes
      in cellular organization and subsequent evolution of functional adult structures.
      Branching morphogenesis is a developmental mechanism by which patterns are
      generated in many developing organs, which is controlled by underlying molecular
      pathways. Understanding the relationship between molecular signaling, cellular
      behavior and resulting morphological change requires quantification and
      categorization of the cellular behavior. In this study, tissue-level and cellular
      changes in developing salivary gland in response to disruption of ROCK-mediated
      signaling by are modeled by building cell-graphs to compute mathematical features
      capturing structural properties at multiple scales. These features were used to
      generate multiscale cell-graph signatures of untreated and ROCK signaling
      disrupted salivary gland organ explants. From confocal images of mouse
      submandibular salivary gland organ explants in which epithelial and mesenchymal
      nuclei were marked, a multiscale feature set capturing global structural
      properties, local structural properties, spectral, and morphological properties
      of the tissues was derived. Six feature selection algorithms and multiway
      modeling of the data was performed to identify distinct subsets of cell graph
      features that can uniquely classify and differentiate between different cell
      populations. Multiscale cell-graph analysis was most effective in classification
      of the tissue state. Cellular and tissue organization, as defined by a multiscale
      subset of cell-graph features, are both quantitatively distinct in epithelial and
      mesenchymal cell types both in the presence and absence of ROCK inhibitors.
      Whereas tensor analysis demonstrate that epithelial tissue was affected the most
      by inhibition of ROCK signaling, significant multiscale changes in mesenchymal
      tissue organization were identified with this analysis that were not identified
      in previous biological studies. We here show how to define and calculate a
      multiscale feature set as an effective computational approach to identify and
      quantify changes at multiple biological scales and to distinguish between
      different states in developing tissues.

PMID- 22403725
TI  - Methylation of Wnt7a is modulated by DNMT1 and cigarette smoke condensate in non
      small cell lung cancer.
AB  - Wnt7a is known to be a tumor suppressor that is lost in NSCLC, but no mechanism
      of loss has been established. Methylation of promoter regions has been
      established as a common mechanism of loss of tumor suppressor expression in
      NSCLC. We previously demonstrated that loss of Wnt7a in non-transformed lung
      epithelial cell lines led to increased cell growth, altered 3-D culture growth,
      and increased migration. The Wnt7a promoter has a higher percentage of
      methylation in NSCLC tumor tissue compared to matched normal lung tissue and
      methylation of the promoter region leads to decreased activity. We treated H157
      and H1299 NSCLC cell lines with 5-Aza-2'-deoxycytidine and detected loss of Wnt7a
      promoter methylation, increased Wnt7a expression, and increased activity of the
      Wnt7a lung signaling pathway. When DNMT1 expression was knocked down by shRNA,
      expression of Wnt7a increased and methylation decreased. Together these data
      suggest that in NSCLC, Wnt7a is lost by methylation in a subset of tumors and
      that this methylation is maintained by DNMT1. Restoration of Wnt7a expression
      through demethylation could be an important therapeutic approach in the treatment
      of NSCLC.

PMID- 22403726
TI  - Differential analysis of ovarian and endometrial cancers identifies a methylator
      phenotype.
AB  - Despite improved outcomes in the past 30 years, less than half of all women
      diagnosed with epithelial ovarian cancer live five years beyond their diagnosis.
      Although typically treated as a single disease, epithelial ovarian cancer
      includes several distinct histological subtypes, such as papillary serous and
      endometrioid carcinomas. To address whether the morphological differences seen in
      these carcinomas represent distinct characteristics at the molecular level we
      analyzed DNA methylation patterns in 11 papillary serous tumors, 9 endometrioid
      ovarian tumors, 4 normal fallopian tube samples and 6 normal endometrial tissues,
      plus 8 normal fallopian tube and 4 serous samples from TCGA. For comparison
      within the endometrioid subtype we added 6 primary uterine endometrioid tumors
      and 5 endometrioid metastases from uterus to ovary. Data was obtained from 27,578
      CpG dinucleotides occurring in or near promoter regions of 14,495 genes. We
      identified 36 locations with significant increases or decreases in methylation in
      comparisons of serous tumors and normal fallopian tube samples. Moreover,
      unsupervised clustering techniques applied to all samples showed three major
      profiles comprising mostly normal samples, serous tumors, and endometrioid tumors
      including ovarian, uterine and metastatic origins. The clustering analysis
      identified 60 differentially methylated sites between the serous group and the
      normal group. An unrelated set of 25 serous tumors validated the reproducibility
      of the methylation patterns. In contrast, >1,000 genes were differentially
      methylated between endometrioid tumors and normal samples. This finding is
      consistent with a generalized regulatory disruption caused by a methylator
      phenotype. Through DNA methylation analyses we have identified genes with known
      roles in ovarian carcinoma etiology, whereas pathway analyses provided biological
      insight to the role of novel genes. Our finding of differences between serous and
      endometrioid ovarian tumors indicates that intervention strategies could be
      developed to specifically address subtypes of epithelial ovarian cancer.

PMID- 22403727
TI  - A mitochondria-dependent pathway mediates the apoptosis of GSE-induced yeast.
AB  - Grapefruit seed extract (GSE), which has powerful anti-fungal activity, can
      induce apoptosis in S. cerevisiae. The yeast cells underwent apoptosis as
      determined by testing for apoptotic markers of DNA cleavage and typical chromatin
      condensation by Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End
      Labeling (TUNEL) and 4,6'-diaminidino-2-phenylindole (DAPI) staining and electron
      microscopy. The changes of DeltaPsimt (mitochondrial transmembrane potential) and
      ROS (reactive oxygen species) indicated that the mitochondria took part in the
      apoptotic process. Changes in this process detected by metabonomics and
      proteomics revealed that the yeast cells tenaciously resisted adversity. Proteins
      related to redox, cellular structure, membrane, energy and DNA repair were
      significantly increased. In this study, the relative changes in the levels of
      proteins and metabolites showed the tenacious resistance of yeast cells. However,
      GSE induced apoptosis in the yeast cells by destruction of the mitochondrial 60 S
      ribosomal protein, L14-A, and prevented the conversion of pantothenic acid to
      coenzyme A (CoA). The relationship between the proteins and metabolites was
      analyzed by orthogonal projections to latent structures (OPLS). We found that the
      changes of the metabolites and the protein changes had relevant consistency.

PMID- 22403728
TI  - In vitro neutralisation of rotavirus infection by two broadly specific
      recombinant monovalent llama-derived antibody fragments.
AB  - Rotavirus is the main cause of viral gastroenteritis in young children.
      Therefore, the development of inexpensive antiviral products for the prevention
      and/or treatment of rotavirus disease remains a priority. Previously we have
      shown that a recombinant monovalent antibody fragment (referred to as Anti
      Rotavirus Proteins or ARP1) derived from a heavy chain antibody of a llama
      immunised with rotavirus was able to neutralise rotavirus infection in a mouse
      model system. In the present work we investigated the specificity and
      neutralising activity of two llama antibody fragments, ARP1 and ARP3, against 13
      cell culture adapted rotavirus strains of diverse genotypes. In addition,
      immunocapture electron microscopy (IEM) was performed to determine binding of
      ARP1 to clinical isolates and cell culture adapted strains. ARP1 and ARP3 were
      able to neutralise a broad variety of rotavirus serotypes/genotypes in vitro, and
      in addition, IEM showed specific binding to a variety of cell adapted strains as
      well as strains from clinical specimens. These results indicated that these
      molecules could potentially be used as immunoprophylactic and/or
      immunotherapeutic products for the prevention and/or treatment of infection of a
      broad range of clinically relevant rotavirus strains.

PMID- 22403729
TI  - Nitrosative and oxidative stresses contribute to post-ischemic liver injury
      following severe hemorrhagic shock: the role of hypoxemic resuscitation.
AB  - PURPOSE: Hemorrhagic shock and resuscitation is frequently associated with liver
      ischemia-reperfusion injury. The aim of the study was to investigate whether
      hypoxemic resuscitation attenuates liver injury. METHODS: Anesthetized,
      mechanically ventilated New Zealand white rabbits were exsanguinated to a mean
      arterial pressure of 30 mmHg for 60 minutes. Resuscitation under normoxemia
      (Normox-Res group, n = 16, PaO(2) = 95-105 mmHg) or hypoxemia (Hypox-Res group, n
      = 15, PaO(2) = 35-40 mmHg) followed, modifying the FiO(2). Animals not subjected
      to shock constituted the sham group (n = 11, PaO(2) = 95-105 mmHg). Indices of
      the inflammatory, oxidative and nitrosative response were measured and
      histopathological and immunohistochemical studies of the liver were performed.
      RESULTS: Normox-Res group animals exhibited increased serum alanine
      aminotransferase, tumor necrosis factor--alpha, interleukin (IL) -1beta and IL-6
      levels compared with Hypox-Res and sham groups. Reactive oxygen species
      generation, malondialdehyde formation and myeloperoxidase activity were all
      elevated in Normox-Res rabbits compared with Hypox-Res and sham groups.
      Similarly, endothelial NO synthase and inducible NO synthase mRNA expression was
      up-regulated and nitrotyrosine immunostaining increased in animals resuscitated
      normoxemically, indicating a more intense nitrosative stress. Hypox-Res animals
      demonstrated a less prominent histopathologic injury which was similar to sham
      animals. CONCLUSIONS: Hypoxemic resuscitation prevents liver reperfusion injury
      through attenuation of the inflammatory response and oxidative and nitrosative
      stresses.

PMID- 22403730
TI  - Restricted morphological and behavioral abnormalities following ablation of beta
      actin in the brain.
AB  - The local translation of beta-actin is one mechanism proposed to regulate
      spatially-restricted actin polymerization crucial for nearly all aspects of
      neuronal development and function. However, the physiological significance of
      localized beta-actin translation in neurons has not yet been demonstrated in
      vivo. To investigate the role of beta-actin in the mammalian central nervous
      system (CNS), we characterized brain structure and function in a CNS-specific
      beta-actin knock-out mouse (CNS-ActbKO). beta-actin was rapidly ablated in the
      embryonic mouse brain, but total actin levels were maintained through
      upregulation of other actin isoforms during development. CNS-ActbKO mice
      exhibited partial perinatal lethality while survivors presented with surprisingly
      restricted histological abnormalities localized to the hippocampus and
      cerebellum. These tissue morphology defects correlated with profound
      hyperactivity as well as cognitive and maternal behavior impairments. Finally, we
      also identified localized defects in axonal crossing of the corpus callosum in
      CNS-ActbKO mice. These restricted defects occurred despite the fact that primary
      neurons lacking beta-actin in culture were morphologically normal. Altogether, we
      identified novel roles for beta-actin in promoting complex CNS tissue
      architecture while also demonstrating that distinct functions for the
      ubiquitously expressed beta-actin are surprisingly restricted in vivo.

PMID- 22403731
TI  - Role of ER stress response in photodynamic therapy: ROS generated in different
      subcellular compartments trigger diverse cell death pathways.
AB  - We have analyzed the molecular mechanisms of photoinduced cell death using
      porphyrins with similar structure differing only in the position of the ethylene
      glycol (EG) chain on the phenyl ring. Meta- and para-positioned EG chains
      targeted porphyrins to different subcellular compartments. After photoactivation,
      both types of derivatives induced death of tumor cells via reactive oxygen
      species (ROS). Para derivatives pTPP(EG)4 and pTPPF(EG)4 primarily accumulated in
      lysosomes activated the p38 MAP kinase cascade, which in turn induced the
      mitochondrial apoptotic pathway. In contrast, meta porphyrin derivative mTPP(EG)4
      localized in the endoplasmic reticulum (ER) induced dramatic changes in Ca(2+)
      homeostasis manifested by Ca(2+) rise in the cytoplasm, activation of calpains
      and stress caspase-12 or caspase-4. ER stress developed into unfolded protein
      response. Immediately after irradiation the PERK pathway was activated through
      phosphorylation of PERK, eIF2alpha and induction of transcription factors ATF4
      and CHOP, which regulate stress response genes. PERK knockdown and PERK
      deficiency protected cells against mTPP(EG)4-mediated apoptosis, confirming the
      causative role of the PERK pathway.

PMID- 22403732
TI  - Sequences sufficient for programming imprinted germline DNA methylation defined.
AB  - Epigenetic marks are fundamental to normal development, but little is known about
      signals that dictate their placement. Insights have been provided by studies of
      imprinted loci in mammals, where monoallelic expression is epigenetically
      controlled. Imprinted expression is regulated by DNA methylation programmed
      during gametogenesis in a sex-specific manner and maintained after fertilization.
      At Rasgrf1 in mouse, paternal-specific DNA methylation on a differential
      methylation domain (DMD) requires downstream tandem repeats. The DMD and repeats
      constitute a binary switch regulating paternal-specific expression. Here, we
      define sequences sufficient for imprinted methylation using two transgenic mouse
      lines: One carries the entire Rasgrf1 cluster (RC); the second carries only the
      DMD and repeats (DR) from Rasgrf1. The RC transgene recapitulated all aspects of
      imprinting seen at the endogenous locus. DR underwent proper DNA methylation
      establishment in sperm and erasure in oocytes, indicating the DMD and repeats are
      sufficient to program imprinted DNA methylation in germlines. Both transgenes
      produce a DMD-spanning pit-RNA, previously shown to be necessary for imprinted
      DNA methylation at the endogenous locus. We show that when pit-RNA expression is
      controlled by the repeats, it regulates DNA methylation in cis only and not in
      trans. Interestingly, pedigree history dictated whether established DR
      methylation patterns were maintained after fertilization. When DR was paternally
      transmitted followed by maternal transmission, the unmethylated state that was
      properly established in the female germlines could not be maintained. This
      provides a model for transgenerational epigenetic inheritance in mice.

PMID- 22403733
TI  - A highly sensitive quantitative real-time PCR assay for determination of mutant
      JAK2 exon 12 allele burden.
AB  - Mutations in the Janus kinase 2 (JAK2) gene have become an important identifier
      for the Philadelphia-chromosome negative chronic myeloproliferative neoplasms. In
      contrast to the JAK2V617F mutation, the large number of JAK2 exon 12 mutations
      has challenged the development of quantitative assays. We present a highly
      sensitive real-time quantitative PCR assay for determination of the mutant allele
      burden of JAK2 exon 12 mutations. In combination with high resolution melting
      analysis and sequencing the assay identified six patients carrying previously
      described JAK2 exon 12 mutations and one novel mutation. Two patients were
      homozygous with a high mutant allele burden, whereas one of the heterozygous
      patients had a very low mutant allele burden. The allele burden in the peripheral
      blood resembled that of the bone marrow, except for the patient with low allele
      burden. Myeloid and lymphoid cell populations were isolated by cell sorting and
      quantitative PCR revealed similar mutant allele burdens in CD16+ granulocytes and
      peripheral blood. The mutations were also detected in B-lymphocytes in half of
      the patients at a low allele burden. In conclusion, our highly sensitive assay
      provides an important tool for quantitative monitoring of the mutant allele
      burden and accordingly also for determining the impact of treatment with
      interferon-alpha-2, shown to induce molecular remission in JAK2V617F-positive
      patients, which may be a future treatment option for JAK2 exon 12-positive
      patients as well.

PMID- 22403734
TI  - The effect of intra-abdominal hypertension incorporating severe acute
      pancreatitis in a porcine model.
AB  - INTRODUCTION: Abdominal compartment syndrome (ACS) and intra abdominal
      hypertension(IAH) are common clinical findings in patients with severe acute
      pancreatitis(SAP). It is thought that an increased intra abdominal pressure(IAP)
      is associated with poor prognosis in SAP patients. But the detailed effect of
      IAH/ACS on different organ system is not clear. The aim of this study was to
      assess the effect of SAP combined with IAH on hemodynamics, systemic oxygenation,
      and organ damage in a 12 h lasting porcine model. MEASUREMENTS AND METHODS:
      Following baseline registrations, a total of 30 animals were divided into 5
      groups (6 animals in each group): SAP+IAP30 group, SAP+IAP20 group, SAP group,
      IAP30 group(sham-operated but without SAP) and sham-operated group. We used a
      N(2) pneumoperitoneum to induce different levels of IAH and retrograde intra
      ductal infusion of sodium taurocholate to induce SAP. The investigation period
      was 12 h. Hemodynamic parameters (CO, HR, MAP, CVP), urine output, oxygenation
      parameters(e.g., S(v)O(2), PO(2), PaCO(2)), peak inspiratory pressure, as well as
      serum parameters (e.g., ALT, amylase, lactate, creatinine) were recorded.
      Histological examination of liver, intestine, pancreas, and lung was performed.
      MAIN RESULTS: Cardiac output significantly decreased in the SAP+IAH animals
      compared with other groups. Furthermore, AST, creatinine, SUN and lactate showed
      similar increasing tendency paralleled with profoundly decrease in S(v)O(2). The
      histopathological analyses also revealed higher grade injury of liver, intestine,
      pancreas and lung in the SAP+IAH groups. However, few differences were found
      between the two SAP+IAH groups with different levels of IAP. CONCLUSIONS: Our
      newly developed porcine SAP+IAH model demonstrated that there were remarkable
      effects on global hemodynamics, oxygenation and organ function in response to
      sustained IAH of 12 h combined with SAP. Moreover, our model should be helpful to
      study the mechanisms of IAH/ACS-induced exacerbation and to optimize the
      treatment strategies for counteracting the development of organ dysfunction.

PMID- 22403735
TI  - Calcium-sensing receptor and aquaporin 2 interplay in hypercalciuria-associated
      renal concentrating defect in humans. An in vivo and in vitro study.
AB  - One mechanism proposed for reducing the risk of calcium renal stones is
      activation of the calcium-sensing receptor (CaR) on the apical membranes of
      collecting duct principal cells by high luminal calcium. This would reduce the
      abundance of aquaporin-2 (AQP2) and in turn the rate of water reabsorption. While
      evidence in cells and in hypercalciuric animal models supports this hypothesis,
      the relevance of the interplay between the CaR and AQP2 in humans is not clear.
      This paper reports for the first time a detailed correlation between urinary AQP2
      excretion under acute vasopressin action (DDAVP treatment) in hypercalciuric
      subjects and in parallel analyzes AQP2-CaR crosstalk in a mouse collecting duct
      cell line (MCD4) expressing endogenous and functional CaR. In normocalciurics,
      DDAVP administration resulted in a significant increase in AQP2 excretion
      paralleled by an increase in urinary osmolality indicating a physiological
      response to DDAVP. In contrast, in hypercalciurics, baseline AQP2 excretion was
      high and did not significantly increase after DDAVP. Moreover DDAVP treatment was
      accompanied by a less pronounced increase in urinary osmolality. These data
      indicate reduced urinary concentrating ability in response to vasopressin in
      hypercalciurics. Consistent with these results, biotinylation experiments in MCD4
      cells revealed that membrane AQP2 expression in unstimulated cells exposed to CaR
      agonists was higher than in control cells and did not increase significantly in
      response to short term exposure to forskolin (FK). Interestingly, we found that
      CaR activation by specific agonists reduced the increase in cAMP and prevented
      any reduction in Rho activity in response to FK, two crucial pathways for AQP2
      translocation. These data support the hypothesis that CaR-AQP2 interplay
      represents an internal renal defense to mitigate the effects of hypercalciuria on
      the risk of calcium precipitation during antidiuresis. This mechanism and
      possibly reduced medulla tonicity may explain the lower concentrating ability
      observed in hypercalciuric patients.

PMID- 22403736
TI  - Regional endothermy in a coral reef fish?
AB  - Although a few pelagic species exhibit regional endothermy, most fish are
      regarded as ectotherms. However, we document significant regional endothermy in a
      benthic reef fish. Individual steephead parrotfish, Chlorurus microrhinos
      (Labridae, formerly Scaridae) were tagged and their internal temperatures were
      monitored for a 24 h period using active acoustic telemetry. At night, on the
      reef, C. microrhinos were found to maintain a consistent average peritoneal
      cavity temperature 0.16 +/- 0.005  degrees C (SE) warmer than ambient. Diurnal
      internal temperatures were highly variable for individuals monitored on the reef,
      while in tank-based trials, peritoneal cavity temperatures tracked environmental
      temperatures. The mechanisms responsible for a departure of the peritoneal cavity
      temperature from environmental temperature occurred in C. microrhinos are not yet
      understood. However, the diet and behavior of the species suggests that heat in
      the peritoneal cavity may result primarily from endogenous thermogenesis coupled
      with physiological heat retention mechanisms. The presence of limited endothermy
      in C. microrhinos indicates that a degree of uncertainty may exist in the manner
      that reef fish respond to their thermal environment. At the very least, they do
      not always appear to respond to environmental temperatures as neutral thermal
      vessels and do display limited, but significant, visceral warming.

PMID- 22403737
TI  - Lymph node, peritoneal and bone marrow micrometastases in gastric cancer: Their
      clinical significance.
AB  - The 7th TNM classification clearly states that micrometastases detected by
      morphological techniques (HE stain and immunohistochemistry) should always be
      reported and calculated in the staging of the disease (pN1mi or M1), while
      patients in whom micrometastases are detected by non-morphological techniques
      (e.g., flow cytometry, reverse-transcriptase polymerase chain reaction) should
      still be classified as N0 or M0. In gastric cancer patients, micrometastases have
      been detected in lymph nodes, the peritoneal cavity and bone marrow. However, the
      clinical implications and/or their prognostic significance are still a matter of
      debate. Current literature suggests that lymph node micrometastases should be
      encountered for the loco-regional staging of the disease, while skip lymph node
      micrometastases should also be encountered in the total number of infiltrated
      lymph nodes. Peritoneal fluid cytology examination should be obligatorily
      performed in pT3 or pT4 tumors. A positive cytology classifies gastric cancer
      patients as stage IV. Although a curative resection is not precluded, these
      patients face an overall dismal prognosis. Whether patients with a positive
      cytology should be treated similarly to patients with macroscopic peritoneal
      recurrence should be evaluated further. Gastric cancer cells are detected with
      high incidence in the bone marrow. However, the published results make comparison
      of data between groups almost impossible due to severe methodological problems.
      If these methodological problems are overcome in the future, specific target
      therapies may be designed for specific groups of patients.

PMID- 22403738
TI  - Simultaneous intraductal papillary neoplasms of the bile duct and pancreas
      treated with chemoradiotherapy.
AB  - Some authors have suggested that intraductal papillary mucinous neoplasms of the
      bile duct (IPMN-B) could be the the biliary counterpart of IPMN of the pancreas
      (IPMN-P) since they share several clinical-pathological features. These include
      prominent intraductal papillary proliferation pattern, a gastrointestinal
      phenotype, frequent mucin hyper-secretion and progression to mucinous carcinoma.
      To date there are just four reported cases of patients with synchronous IPMN-B
      and IPMN-P all of which were treated surgically. We hereby report the case of a
      76-year-old woman who was incidentally diagnosed with both an asymptomatic 3 cm
      bulky fluid lesion obstructing the bile duct lumen, diagnosed as a malignant IPMN
      B, and synchronous multiple pancreatic cystic lesions (10-13 mm) communicating
      with an irregular Wirsung, diagnosed as branch duct IPMN-P. Since surgery was
      ruled-out because of the patient's age and preferences, she underwent a
      conservative management regimen comprising both chemotherapy and radiotherapy.
      This was effective in decreasing the mass size and in resolving subsequent
      jaundice. This is also the first reported case of IPMN-B successfully treated
      with chemoradiotherapy. Clinicians should consider medical treatment as an option
      in this clinical scenario, in patients who may be unfit for surgery.

PMID- 22403739
TI  - Running in the family: MALT lymphoma and autoimmune disease in mother and
      daughter.
AB  - Gastric B-cell lymphoma of the mucosa associated lymphoid tissue (MALT) lymphoma
      is one of the most common forms of extranodal lymphoma. In addition to infection
      with Helicobacter pylori (H. pylori), the presence of an underlying autoimmune
      disease has also been associated with MALT lymphoma development. To date, no
      familial predisposition for MALT lymphomas has been reported as opposed to other
      types of lymphoma. A 65-year-old woman was admitted at our institution in 1998
      with a diagnosis of H. pylori positive gastric MALT lymphoma and the presence of
      chronic autoimmune thyroiditis was established on further work-up. H. pylori
      eradication did not result in regression of the lymphoma and RT-PCR showed the
      presence of the t(11;18)(q21;q21) translocation. About 1.5 years after H. pylori
      eradication, chemotherapy with cladribine resulted in complete remission. Due to
      lymphoma recurrence 13 mo later, radiotherapy to the stomach (46 Gy) resulted in
      minimal residual disease without further progression. The patient developed a
      second malignancy (Epstein-Bar virus-associated anaplastic large cell lymphoma in
      the mediastinum) in 2004 which initially responded to two courses of
      chemotherapy, but she refused further therapy and died of progressive lymphoma in
      2006. In 2008, her 55 years old daughter with a long standing Sjogren's syndrome
      was diagnosed with MALT lymphoma of the right parotid, but no evidence of gastric
      involvement or H. pylori infection was found. Currently, she is alive without
      therapy and undergoing regular check-ups. To our knowledge, this is the first
      report of MALT lymphoma in a first-degree relative of a patient with gastric MALT
      lymphoma in the context of two autoimmune diseases without a clearly established
      familial background.

PMID- 22403740
TI  - Epigenetic control of an oncogenic microRNA, miR-155, by BRCA1.

PMID- 22403741
TI  - Curtailing side effects in chemotherapy: a tale of PKCdelta in cisplatin
      treatment.
AB  - The efficacy of chemotherapy is often limited by side effects in normal tissues.
      This is exemplified by cisplatin, a widely used anti-cancer drug that may induce
      serious toxicity in normal tissues and organs including the kidneys. Decades of
      research have delineated multiple signaling pathways that lead to kidney cell
      injury and death during cisplatin treatment. However, the same signaling pathways
      may also be activated in cancer cells and be responsible for the chemotherapeutic
      effects of cisplatin in tumors and, as a result, blockade of these pathways is
      expected to reduce the side effects as well as the anti-cancer efficacy. Thus, to
      effectively curtail the side effects, it is imperative to elucidate and target
      the cell killing mechanisms that are specific to normal (and not cancer) tissues.
      Our recent work identified protein kinase C delta (PKCdelta) as a new and
      critical mediator of cisplatin-induced kidney cell injury and death. Importantly,
      inhibition of PKCdelta enhanced the chemotherapeutic effects of cisplatin in
      several tumor models while alleviating the side effect in kidneys, opening a new
      avenue for normal tissue protection during chemotherapy.

PMID- 22403742
TI  - Split thickness skin grafts for the treatment of non-healing foot and leg ulcers
      in patients with diabetes: a retrospective review.
AB  - We retrospectively reviewed 107 diabetic patients who received a split thickness
      skin graft (STSG) for treatment of a non-healing diabetic foot or leg ulcer to
      describe healing times based on patient characteristics, comorbidities or
      complications. The minimum follow-up was 6 months from the time of STSG
      application. The mean time to healing among all patients was 5.1 weeks (3 to 16
      weeks). The mean healing time for patients with complications was 12.0 weeks (10
      to 16 weeks) while the mean healing time for those without complications was 4.9
      weeks (3 to 10 weeks). Overall complication rate was 2.8%. Patients with a STSG
      take of less than 95% had a mean healing time of 7.9 weeks compared to 4.8 weeks
      for those with a STSG take of 100% (p<0.001). The use of autologous STSG for
      treatment of non-healing diabetic foot and leg wounds is a viable method for soft
      tissue closure and may present a low complication rate and a satisfactory rate of
      healing.

PMID- 22403743
TI  - Isotopic evidence of plutonium release into the environment from the Fukushima
      DNPP accident.
AB  - The Fukushima Daiichi nuclear power plant (DNPP) accident caused massive releases
      of radioactivity into the environment. The released highly volatile fission
      products, such as (129m)Te, (131)I, (134)Cs, (136)Cs and (137)Cs were found to be
      widely distributed in Fukushima and its adjacent prefectures in eastern Japan.
      However, the release of non-volatile actinides, in particular, Pu isotopes
      remains uncertain almost one year after the accident. Here we report the isotopic
      evidence for the release of Pu into the atmosphere and deposition on the ground
      in northwest and south of the Fukushima DNPP in the 20-30 km zones. The high
      activity ratio of (241)Pu/(239+240)Pu (> 100) from the Fukushima DNPP accident
      highlights the need for long-term (241)Pu dose assessment, and the ingrowth of
      (241)Am. The results are important for the estimation of reactor damage and have
      significant implication in the strategy of decontamination.

PMID- 22403744
TI  - Premenstrual enhancement of snake detection in visual search in healthy women.
AB  - It is well known that adult humans detect images of snakes as targets more
      quickly than images of flowers as targets whether the images are in color or gray
      scale. When such visual searches were performed by a total of 60 adult
      premenopausal healthy women in the present study to examine whether their
      performance would fluctuate across the phases of the menstrual cycle, snake
      detection was found to become temporarily enhanced during the luteal phase as
      compared to early or late follicular phases. This is the first demonstration of
      the existence of within-individual variation of the activity of the fear module,
      as a predictable change in cognitive strength, which appears likely to be due to
      the hormonal changes that occur in the menstrual cycle of healthy women.

PMID- 22403746
TI  - Comparison of laparoscopy-assisted and totally laparoscopic Billroth-II distal
      gastrectomy for gastric cancer.
AB  - PURPOSE: In laparoscopic distal gastrectomy for gastric cancer, most surgeons
      prefer extra-corporeal anastomosis because of technical challenges and
      unfamiliarity with intra-corporeal anastomosis. Herein, we report the feasibility
      and safety of intra-corporeal Billroth-II anastomosis in gastric cancer. METHODS:
      From April 2004 to March 2011, 130 underwent totally laparoscopic distal
      gastrectomy with intra-corporeal Billroth-II reconstruction, and 269 patients
      underwent laparoscopy-assisted distal gastrectomy with extra-corporeal Billroth
      II reconstruction. Surgical efficacies and outcomes between two groups were
      compared. RESULTS: There were no differences in demographics and
      clinicopathological characteristics. The mean operation and reconstruction times
      of totally laparoscopic distal gastrectomy were statistically shorter than
      laparoscopy-assisted distal gastrectomy (P = 0.019; P < 0.001). Anastomosis
      related complications were observed in 11 (8.5%) totally laparoscopic distal
      gastrectomy and 21 (7.8%) laparoscopy-assisted distal gastrectomy patients, and
      the incidence of these events was not significantly different. Post-operative
      hospital stays for totally laparoscopic distal gastrectomy were shorter than
      laparoscopy-assisted distal gastrectomy patients (8.3 +/- 3.2 days vs. 9.9 +/-
      5.3 days, respectively; P = 0.016), and the number of times parenteral analgesic
      administration was required in laparoscopy-assisted distal gastrectomy patients
      was more frequent after surgery. CONCLUSION: Intra-corporeal Billroth-II
      anastomosis is a feasible procedure and can be safely performed with the proper
      experience for laparoscopic distal gastrectomy. This method may be less time
      consuming and may produce a more cosmetic result.

PMID- 22403747
TI  - Can serum interleukin-2 receptor alpha predict lymph node metastasis in early
      gastric cancer?
AB  - PURPOSE: Although local resection like endoscopic mucosal resection for early
      gastric cancer is accepted as a treatment option, one of the most important
      drawbacks of such an approach is the inability to predictlymph node metastasis.
      The aim of this study was to evaluate the serum soluble receptor alpha for
      interleukin-2 (IL-2Ralpha) level as a predictor of lymph node metastasis in the
      patients with early gastric cancer. METHODS: Assessment of pre-operative serum IL
      2Ralpha levels was performed on 86 patients with early gastric cancer treated by
      gastrectomies combined with D2 lymph node resections and 20 healthy controls at
      Samsung Medical Center. Data on patient age and gender, tumor size, depth of
      invasion, histologic differentiation, and endoscopic findings were reviewed post
      operatively. The submucosal lesions were divided into three layers (sm1, sm2, and
      sm3) in accordance with the depth of invasion. RESULTS: Lymph node metastasis was
      observed in 16 patients (18.6%). Statistically, the serum IL-2Ralpha level was an
      important predictive factor of lymph node metastasis in undifferentiated gastric
      cancer, and the cut-off point for the predictive value of serum IL-2Ralpha level
      was 200 U/mL. CONCLUSION: The serum IL-2Ralpha level might be a good predictor of
      lymph node metastasis in undifferentiated early gastric cancer.

PMID- 22403745
TI  - Effects of arterial cannulation stress on regional cerebral blood flow in major
      depressive disorder.
AB  - Individuals with major depressive disorder (MDD) display abnormal
      neurophysiological responses to psychological stress but little is known about
      their neurophysiological responses to physiological stressors. Using [(15)O
      H(2)O] positron emission tomography we assessed whether the regional cerebral
      blood flow (rCBF) response to arterial cannulation differed between patients with
      MDD and healthy controls (HCs). Fifty-one MDD patients and 62 HCs were scanned
      following arterial cannulation and 15 MDD patients and 17 HCs were scanned
      without arterial cannulation. A region-of-interest analysis showed that a
      significantly increased rCBF of the anterior cingulate cortex and right amygdala
      was associated with arterial cannulation in MDD. A whole brain analysis showed
      increased rCBF of the right post-central gyrus, left temporopolar cortex, and
      right amygdala during arterial cannulation in MDD patients. The rCBF in the right
      amygdala was significantly correlated with depression severity. Conceivably, the
      limbic response to invasive physical stress is greater in MDD subjects than in
      HCs.

PMID- 22403748
TI  - The effect of erythromycin on gastrointestinal motility in subtotal
      gastrectomized patients.
AB  - PURPOSE: Our objective was to determine the effect of erythromycin (EM) in
      improving gastrointestinal motility in subtotal gastrectomized patients. We used
      radio-opaque Kolomarks as an objective method. We conducted a prospective,
      controlled clinical trial study of 24 patients. METHODS: All patients underwent
      subtotal gastrectomy with 3 capsules containing Kolomarks (20 markers per 1
      capsule) in the remnant stomach before anastomosis. From the day of the operation
      to the 2nd postoperative day, patients in the EM group began receiving 200 mg of
      EM intravenously for 30 minutes continuously. We counted the number of Kolomarks
      in the stomach, passed by stomach, in rectum, and in stool with serial simple
      abdominal X-ray films on the first postoperative day up to the 7th postoperative
      day. RESULTS: The study population included 14 patients in the control group and
      10 patients in the EM group. The two study groups were compared in terms of their
      characteristics including age, gender, past medical history, cancer stage, and
      operation type. No significant differences were found for the demographics
      between the two groups. We only found a significant difference for the number of
      Kolomarks passed by the stomach on the 3rd postoperative day (P = 0.026).
      CONCLUSION: Our results demonstrated that 200 mg of EM intravenous infusion
      during the postoperative period induced rapid gastric emptying, although it did
      not improve gastrointestinal motility for the entire gastrointestinal tract in
      subtotal gastrectomized patients.

PMID- 22403749
TI  - Association of CTTN polymorphisms with the risk of colorectal cancer.
AB  - PURPOSE: Various studies searching for biomarkers to predict tumor metastasis or
      prognosis in both esophageal squamous cell carcinoma (ESCC) and head and neck
      squamous cell carcinoma (HNSCC) are currently underway. However, few data have
      been reported on its association with colorectal cancer (CRC). Single nucleotide
      polymorphisms (SNPs) are the most common known form of human genetic variation
      and may contribute to an increased susceptibility to cancer including CRC. The
      present study aimed to investigate whether the polymorphisms in the CTTN gene are
      associated with susceptibility to CRC in the Korean population. METHODS: A case
      control study was performed to examine the relationship between the CTTN g.
      9101C>T, g.-8748C>T, and g.72C>T polymorphisms and the risk of CRC. Polymerase
      chain reaction-restriction fragment length polymorphism analysis of g.-8748C>T,
      g.-9101C>T and Taqman analysis of g.72C>T were performed on blood samples from
      218 patients with CRC and 533 control individuals. The g.-9101C>T, g.-8748C>T,
      and g.72C>T SNPs in CTTN and their haplotypes were analyzed. RESULTS: The
      genotype and allele frequencies of g.-9101C>T, g.-8748C>T, and g.72C>T did not
      differ between the patient group and the control group. Further, the haplotype of
      CTTN g.-9101C>T, g.-8748C>T, and g.72C>T did not differ between patient group and
      the control group. However, the genotype and allele frequencies of CTTN g.
      9101C>T were significantly increased in the lymph node positive CRC group
      compared to the control group. CONCLUSION: The CTTN g.-9101C>T polymorphism may
      influence lymph node positive CRC.

PMID- 22403750
TI  - Risk factors of circumferential resection margin involvement in the patients with
      extraperitoneal rectal cancer.
AB  - PURPOSE: Currently, circumferential resection margins (CRM) are used as a
      clinical endpoint in studies on the prognosis of rectal cancer. Although the
      concept of a circumferential resection margin in extraperitoneal rectal cancer
      differs from that in intraperitoneal rectal cancer due to differences in
      anatomical and biologic behaviors, previous reports have provided information on
      CRM involvement in all types of rectal cancer including intraperitoneal lesions.
      Therefore, the aim of this study was to analyze risk factors of CRM involvement
      in extraperitoneal rectal cancer. METHODS: From January 2005 to December 2008,
      306 patients with extraperitoneal rectal cancer were enrolled in a prospectively
      collected database. Multivariate logistic regression analysis was used to
      identify predictors of CRM involvement. RESULTS: The overall rate of CRM
      involvement was found to be 16.0%. Multivariate analysis showed that male sex,
      larger tumor size (>=4 cm), stage higher than T3, nodal metastasis, tumor
      perforation and non-sphincter preserving proctectomy (NSPP) were risk factors for
      CRM involvement. CONCLUSION: Male sex, larger tumor size (>=4 cm), advanced T
      stage, nodal metastasis, tumor perforation, and NSPP are significant risk factors
      of CRM involvement in extraperitoneal rectal cancer. Given that postoperative
      chemoradiotherapy is recommended for patients with a positive CRM, further
      oncologic studies are warranted to ascertain which patients with these risk
      factors would require adjuvant therapy.

PMID- 22403751
TI  - Pain after laparoscopic appendectomy: a comparison of transumbilical single-port
      and conventional laparoscopic surgery.
AB  - PURPOSE: Conventional laparoscopic appendectomy is performed using three ports,
      and single-port appendectomy is an attractive alternative in order to improve
      cosmesis. The aim of this study was to compare pain after transumbilical single
      port laparoscopic appendectomy (SA) with pain after conventional three-port
      laparoscopic appendectomy (TA). METHODS: From April to September 2011, 50
      consecutive patients underwent laparoscopic appendectomy for simple appendicitis
      without gangrene or perforation. Patients who had undergone appendectomy with a
      drainage procedure were excluded. The type of surgery was chosen based on patient
      preference after written informed consent was obtained. The primary endpoint was
      postoperative pain evaluated by the visual analogue scale score and postoperative
      analgesic use. Operative time, recovery of bowel function, and length of hospital
      stay were secondary outcome measures. RESULTS: SA using a SILS port (Covidien)
      was performed in 17 patients. The other 33 patients underwent TA. Pain scores in
      the 24 hours after surgery were higher in patients who underwent SA (P = 0.009).
      The change in postoperative pain score over time was significantly different
      between the two groups (P = 0.021). SA patients received more total doses of
      analgesics (nonsteroidal anti-inflammatory drugs) in the 24 hours following
      surgery, but the difference was not statistically significant. The median
      operative time was longer for SA (P < 0.001). CONCLUSION: Laparoscopic surgeons
      should be concerned about longer operation times and higher immediate
      postoperative pain scores in patients who undergo SA.

PMID- 22403752
TI  - Review of 100 cases of single port laparoscopic cholecystectomy.
AB  - PURPOSE: Single port laparoscopic cholecystectomy (SPLC) is a new advanced
      technique in laparoscopic surgery. Many laparoscopic surgeons seek to gain skill
      in this new technique. However, little data has been accumulated and published
      formally yet. This article reports the achievement of 100 cases of SPLC with the
      hopes it will encourage laparoscopic surgery centers in the early adoption of
      SPLC. METHODS: A retrospective review of 100 prospectively selected cases of SPLC
      was carried out. All patients had received elective SPLC by a single surgeon in
      our center from May 2009 to December 2010. Our review suggests patients'
      character, perioperative data and postoperative outcomes. RESULTS: Forty-two men
      and 58 women with an average age of 45.8 years had received SPLC. Their mean body
      mass index (BMI) was 23.85 kg/m(2). The mean operating time took 76.75 minutes.
      However, operating time was decreased according to the increase of experience of
      SPLC cases. Twenty-one cases were converted to multi-port surgery. BMI, age,
      previous low abdominal surgical history did not seem to affect conversion to
      multi-port surgery. No cases were converted to open surgery. Mean duration of
      hospital stay was 2.18 days. Six patients had experienced complications from
      which they had recovered after conservative treatment. CONCLUSION: SPLC is a safe
      and practicable technique. The operating time is moderate and can be reduced with
      the surgeon's experience. At first, strict criteria was indicated for SPLC,
      however, with surgical experience, the criteria and area of SPLC can be
      broadened. SPLC is occupying a greater domain of conventional laparoscopic
      cholecystectomy.

PMID- 22403753
TI  - Bilateral adrenal pheochromocytoma with a germline L790F mutation in the RET
      oncogene.
AB  - About ten percent of pheochromocytomas are associated with familial syndrome.
      Hereditary pheochromocytoma has characteristics of early onset, multifocality and
      bilaterality. We experienced a case of 44-year-old man with bilateral
      pheochromocytoma without evidence of medullary thyroid cancer. Genetic test
      detected a L790F germline mutation of RET oncogene. The author found a necessity
      for genetic tests in cases of young-age, bilateral pheochromocytoma.

PMID- 22403754
TI  - Large tubular colonic duplication in an adult treated with a small midline
      incision.
AB  - Tubular colonic duplication presenting in adults is rare and difficult to
      diagnose preoperatively. Only a few cases have been reported in the literature.
      We report a case of a 29-year-old lady presenting with a long history of chronic
      constipation, abdominal mass and repeated episodes of abdominal pain. The
      abdominal-pelvic computed tomography scan showed segmental bowel wall thickening
      thought to be small bowel, and dilatation with stasis of intraluminal content.
      The provisional diagnosis was small bowel duplication. She was scheduled for
      single port laparoscopic resection. However, a T-shaped tubular colonic
      duplication at sigmoid colon was found intraoperatively. Resection of the large T
      shaped tubular colonic duplication containing multiple impacted large fecaloma
      and primary anastomosis was performed. There was no perioperative complication.
      We report, herein, the case of a T-shaped tubular colonic duplication at sigmoid
      colon in an adult who was successfully treated through mini-laparotomy assisted
      by single port laparoscopic surgery.

PMID- 22403755
TI  - A hybrid operation in a patient with complex right subclavian artery aneurysm.
AB  - We report a hybrid surgery including endovascular aneurysm repair and debranching
      procedures to treat a patient with a complex right subclavian artery aneurysm.
      The patient was a 70-year-old woman who presented with dry cough and hoarseness.
      The aneurysm was characterized by the absence of a proximal neck, and involvement
      of the origin of the right vertebral artery. She underwent carotid-vertebral
      artery bypass, stent graft from the innomiate artery to the common carotid artery
      and carotid-axillary artery bypass. Great saphenous vein was used for the carotid
      vertebral artery bypass and 7 mm reinforced polytetrafluoroethylene graft was
      used for the carotid-axillary artery bypass. The postoperative course was
      uneventful.

PMID- 22403756
TI  - Report of a case of ischemic colitis with bilaterally patent internal iliac
      arteries after endovascular abdominal aneurysm repair.
AB  - During endovascular aneurysm repair (EVAR), interruption of the internal iliac
      arteries (IIAs) or the inferior mesenteric artery by stents or embolization is
      thought to cause colon ischemia. To minimize this risk, attempts have been made
      to preserve the IIAs using iliac branch devices or IIA revascularization. Here we
      present our experience of colon ischemia after EVAR in a patient with bilaterally
      patent IIAs without evidence of embolism. A 70-year-old man had abdominal pain
      and a ruptured abdominal aortic aneurysm was found. We performed EVAR with custom
      made tube grafts preserving the bilateral IIAs. On postoperative day 2, the
      patient complained of abdominal pain, a sigmoidoscopy was performed revealing
      colon ischemia. On laparotomy, transmural infarction of the sigmoid colon was
      found and resected. Because IIA preservation cannot guarantee protection against
      colon ischemia, surgeons should maintain a high level of suspicion and use
      surveillance liberally after EVAR for early diagnosis of colon ischemia, even if
      both IIAs are preserved.

PMID- 22403757
TI  - [Possibilities for inhibiting tumor-induced angiogenesis: results with multi
      target tyrosine kinase inhibitors].
AB  - Functional blood vasculature is essential for tumor progression. The main
      signalization pathways that play a key role in the survival and growth of tumor
      vessels originate from the VEGF-, PDGF- and FGF tyrosine kinase receptors. In the
      past decade, significant results have been published on receptor tyrosine kinase
      inhibitors (RTKIs). In this paper, the mechanisms of action and the results so
      far available of experimental and clinical studies on multi-target antiangiogenic
      TKIs are discussed. On the one hand, notable achievements have been made recently
      and these drugs are already used in clinical practice in some patient
      populations. On the other hand, the optimal combination and dosage of these
      drugs, selection of the apropriate biomarker and better understanding of the
      conflicting role of PDGFR and FGFR signaling in angiogenesis remain future
      challenges.

PMID- 22403758
TI  - [New perspective in the treatment of chronic myeloid leukemia? gene silencing
      therapy].
AB  - Chronic myeloid leukemia is an incurable white blood cell disease with slow
      progression which affects myeloid stem cells. In the course of chromosome 22
      shortening a fusion oncogene arises whose product, a Bcr-Abl oncoprotein, is a
      continuously expressed tyrosine kinase protein. Beside the opportunity of
      chemotherapy, stem cell therapy and interferon-a therapy, the application of
      tyrosine kinase inhibitors also became widespread in the treatment of the
      disease. Patients bearing the T315I point mutation, however, show resistance
      against all tyrosine kinase inhibitors, which can be managed by dose escalation
      or the combination of therapies. The discovery of RNA interference or gene
      silencing put the therapeutic opportunity of CML in new light. The in vitro
      application of anti-bcr-abl siRNA showed promising results in the causal
      treatment of the disease, feasible for identification of new genes associated to
      the disease, but we do not have sufficient evidence for the safety and efficacy
      of this method in human therapy.

PMID- 22403759
TI  - [Role of PET/CT in diagnosis and treatment of breast cancer -- review of present
      knowledge and perspectives for future research].
AB  - Positron emission tomography (PET) has revolutionized the diagnostic
      opportunities of malignances, however, it has still a controversial role at some
      conditions in the management of breast cancer. The article compares PET alone and
      PET/CT. We review the latest trends of using PET or PET/CT for diagnosis,
      staging, evaluation of the primary tumor and regional lymph node status, as well
      as early detection of recurrence and distant lesions. PET/CT provides new methods
      of assessment of early chemo/endocrine therapy response of locally advanced
      breast cancer. We discuss the development of new radiotracers and their value in
      predicting treatment response, identifying tumor subtypes and finding new
      therapeutic targets by them.

PMID- 22403760
TI  - [Results of the treatment of pediatric osteosarcoma in the Hungarian population].
AB  - The objective of this report was to estimate long-term outcome and prognostic
      factors in children and adolescents with osteosarcoma. To evaluate the efficacy
      of surgery and multiagent chemotherapy for treating osteosarcoma, we reviewed 122
      cases (65 males, 57 females, mean age 13.8 +/- 3.6 years) treated at the Second
      Department of Pediatrics in Budapest between 1988 and 2006. Demographic
      parameters, tumor-related and treatment-related variables, response, overall
      survival (OS) and event-free survival (EFS) were analyzed. The 5-year OS and EFS
      were 68% and 61.5%, respectively. OS of patients without metastasis was 79%,
      while OS with early metastasis was 17%. Survival of patients with amputation
      (n=30) was not significantly different from that of patients with limb-salvage
      surgery (n=82), but all patients without radical surgery died. Gender and
      histological classification had no prognostic significance. Patients with
      localized tumors in extremities had increased survival compared to those with
      axial skeleton tumors (p=0.013). Poor histological response to neoadjuvant
      chemotherapy (rate of survivor tumor cells >10%) was associated with decreased
      survival (p=0.018). Patients under 14 years had better EFS than patients over 14
      years (p=0.008). Our results demonstrate that younger patients with localized
      osteosarcoma of the extremities who receive limb-salvage surgery and chemotherapy
      have an excellent survival.

PMID- 22403761
TI  - [EGFR tyrosine kinase inhibitors in lung cancer management: sensitivity and
      resistance].
AB  - Tailored therapy in lung cancer is one of the most exciting fields in
      translational research and also a nice example of fruitful collaboration between
      pulmonologists, clinical oncologists, pathologists and molecular biologists. This
      article, through a dialogue between a pathologist-clinician and a molecular
      biologist-pharmacologist, gives an overview about the most important questions on
      molecular targeted therapy in clinical practice, especially, EGFR-TKI treatment,
      EGFR activating mutations, as well as primary and acquired resistance.

PMID- 22403762
TI  - [Systemic sclerosis in a patient suffering from breast cancer].
AB  - Scleroderma is the general disease of the connective tissue, which can be
      characterized by the proliferation of the connective tissue and fibrosis.
      According to the results of international studies scleroderma is frequently
      accompanied by neoplastic diseases, among which the most often occurring is the
      neoplastic pathology of the breast and the lungs. In May 2007, in the case of our
      40-year-old woman patient the histological examination of the tumor we noticed in
      the left breast verified invasive carcinoma. In December 2007, after neoadjuvant
      chemotherapy she had a left mastectomy and then she was given postoperative
      irradiation, hormone therapy and trastuzumab (Herceptin) treatment, which was
      suspended in December 2008 due to oedema and fibrosis all over the body. In May
      2009 she first visited the immunology outpatient department of our clinic, where
      we started her examination because of our suspicion of scleroderma and her
      cutaneous fibrosis symptoms, which was established on the basis of the
      examinations (immunoserology, body plethysmography, diffusing capacity of the
      lung for carbon monoxide, capillary microscopy, barium swallow) and her symptoms.
      She was given a conservative therapy (pentoxyphylline, amlodipine,
      nitroglycerin). Scleroderma arising after the neoplastic process of the breast is
      usually much more progressive than the primary disease. International reports
      also show a close correlation between breast cancer and the development of
      scleroderma, but its exact mechanism is not yet clear.

PMID- 22403763
TI  - [Synchronous tumors of the female genital tract: triple malignant and one benign
      tumor].
AB  - Synchronous tumors of the female genital tract are rare, accounting for 0.7-1.8%
      of all cases. Double synchronous tumors are most often mentioned in the
      literature. Reviewing the English literature on this topic, we have found only
      one case report of a triple synchronous tumor. The 55-year-old patient mentioned
      in our case has had advanced diabetes mellitus, and has been treated with
      corticosteroid therapy for a long time because of chronic obstructive pulmonary
      disease (COPD). She was examined because of her vulvar tumor. During the
      diagnostic procedure, cervical and endometrial malignant tumors and a benign
      ovarian cyst have also been found. This event brings to our attention the fact
      that we should be prepared to manage synchronous even triple malignant
      gynecological tumors.

PMID- 22403764
TI  - The electrochemical performance of graphene modified electrodes: an analytical
      perspective.
AB  - We explore the use of graphene modified electrodes towards the electroanalytical
      sensing of various analytes, namely dopamine hydrochloride, uric acid,
      acetaminophen and p-benzoquinone via cyclic voltammetry. In line with literature
      methodologies and to investigate the full-implications of employing graphene in
      this electrochemical context, we modify electrode substrates that exhibit either
      fast or slow electron transfer kinetics (edge- or basal- plane pyrolytic graphite
      electrodes respectively) with well characterised commercially available graphene
      that has not been chemically treated, is free from surfactants and as a result of
      its fabrication has an extremely low oxygen content, allowing the true
      electroanalytical applicability of graphene to be properly de-convoluted and
      determined. In comparison to the unmodified underlying electrode substrates
      (constructed from graphite), we find that graphene exhibits a reduced analytical
      performance in terms of sensitivity, linearity and observed detection limits
      towards each of the various analytes studied within. Owing to graphene's
      structural composition, low proportion of edge plane sites and consequent slow
      heterogeneous electron transfer rates, there appears to be no advantages, for the
      analytes studied here, of employing graphene in this electroanalytical context.

PMID- 22403765
TI  - Design of an in-house ambient pressure AP-XPS using a bench-top X-ray source and
      the surface chemistry of ceria under reaction conditions.
AB  - A new in-house ambient pressure XPS (AP-XPS) was designed for the study of
      surfaces of materials under reaction conditions and during catalysis. Unique
      features of this in-house AP-XPS are the use of monochromated Al Kalpha and
      integration of a minimized reaction cell, and working conditions of up to 500 
      degrees C in gases of tens of Torr. Generation of oxygen vacancies on ceria and
      filling them with oxygen atoms were characterized in operando.

PMID- 22403766
TI  - A small change in molecular structure, a big difference in the AIEE mechanism.
AB  - An anthracene carboxamide derivative of the excited-state intramolecular proton
      transfer compound of 2-(2'-hydroxyphenyl)benzothiazole has been newly developed
      to produce the prominent characteristics of aggregation-induced enhanced emission
      (AIEE) with a high solid-state fluorescence quantum efficiency of 78.1%. Compared
      with our previously reported phenyl carboxamide derivatives, a small tailoring of
      the molecular structure was found to result in a big difference in the dominant
      factor of the AIEE mechanism. In the phenyl carboxamide derivatives, the dominant
      factor of the AIEE mechanism is the restriction of the twisted intramolecular
      charge transfer (TICT) of the enol excited state, regardless of their different
      aggregation modes. In the anthracene carboxamide derivative, N-(3
      (benzo[d]thiazol-2-yl)-4-hydroxyphenyl) anthracene-9-carboxamide, the AIEE
      characteristics are not dependent on the restriction of TICT, but mainly
      attributed to the cooperative effects of J-aggregation and the restriction of the
      cis-trans tautomerization in the keto excited state. A specific N...pi
      interaction was found to be the main driving force for this J-aggregation, as
      revealed by the single crystal analysis. The AIEE mechanism of this anthracene
      carboxamide derivative was studied in detail through photophysical investigations
      and theoretical calculations. On the basis of its AIEE characteristics, a stable
      non-doped organic light-emitting diode was achieved, with high color purity and a
      remarkably low efficiency roll-off.

PMID- 22403767
TI  - Photoinduced electron transfer between various coumarin analogues and N,N
      dimethylaniline inside niosome, a nonionic innocuous polyethylene glycol-based
      surfactant assembly.
AB  - Photoinduced electron transfer (ET) reactions between coumarin dyes and N,N
      dimethylaniline have been investigated inside niosome, a nonionic innocuous
      polyethylene glycol (PEG)-based surfactant assembly using steady state and time
      resolved fluorescence measurements. The location of coumarin dyes inside the
      bilayer headgroup region of niosome has been reported and it was verified by
      determination of the high distribution coefficient of all the dyes inside niosome
      compared to bulk water. Fluorescence anisotropy parameters of the dyes inside
      niosome are also in good correlation with the above inference about their
      location. Bimolecular diffusion guided rates inside niosome were determined by
      comparing the microviscosities inside niosome and in acetonitrile and butanol
      solutions and it was found that diffusion of the donor and the acceptor is much
      slower than the ET rates, implying insignificant role of reactant diffusion in ET
      reaction inside niosome. We have observed a Marcus inversion region in our
      restricted media, which shows maxima at lower exergonicity. Such behavior has
      been demonstrated by the presence of nonequilibrium solvent excited state using
      two dimensional ET (2DET) theory. Unusually high quenching rates of two coumarins
      C-152 and C-152A inside niosome were explained by the presence of a stable non
      fluorescent twisted intramolecular charge transfer (TICT) state along with an
      emissive intramolecular charge transfer (ICT) state. Moreover, intermolecular
      hydrogen bonding between carbonyl oxygens of these two dyes and water in their
      non-emissive and emissive charge transfer states also plays a key role in their
      dynamical exchange with each other [G.-J. Zhao and K.-L. Han, Acc. Chem. Res.,
      2011].

PMID- 22403768
TI  - First-in-man use of a novel embolic protection device for patients undergoing
      transcatheter aortic valve implantation.
AB  - AIMS: We describe the first-in-human experience with a novel cerebral embolic
      protection device used during transcatheter aortic valve implantation (TAVI). One
      current challenge of TAVI is the reduction of procedural stroke. Procedural
      mobilisation of debris is a known source of cerebral embolisation. Mechanical
      protection by transient filtration of cerebral blood flow might reduce the
      embolic burden during TAVI. We aimed to evaluate the feasibility and safety of
      the Claret CE ProTM cerebral protection device in patients undergoing TAVI.
      METHODS AND RESULTS: Patients scheduled for TAVI were prospectively enrolled at
      three centres. The Claret CE ProTM (Claret Medical, Inc. Santa Rosa, CA, USA)
      cerebral protection device was placed via the right radial/brachial artery prior
      to TAVI and was removed after the procedure. The primary endpoint was technical
      success rate. Secondary endpoints encompassed procedural and 30-day stroke rates,
      as well as device-related complications. Deployment of the Claret CE ProTM
      cerebral protection device was intended for use in 40 patients, 35 devices were
      implanted into the aortic arch. Technical success rate with delivery of the
      proximal and distal filter was 60% for the first generation device and 87% for
      the second-generation device. Delivery times for the first-generation device were
      12.4+/-12.1 minutes and 4.4 +/- 2.5 minutes for the second-generation device
      (p<0.05). The quantity of contrast used related to the Claret CE Pro System was
      19.6 +/- 3.8 ml. Captured debris was documented in at least 19 of 35 implanted
      devices (54.3%). No procedural transient ischaemic attacks, minor strokes or
      major strokes occurred. Thirty-day follow-up showed one minor stroke occurring 30
      days after the procedure, and two major strokes both occurring well after the
      patient had completed TAVI. CONCLUSIONS: The use of the Claret CE ProTM system is
      feasible and safe. Capture of debris in more than half of the patients provides
      evidence for the potential to reduce the procedural cerebral embolic burden
      utilising this dedicated filter system during TAVI.

PMID- 22403771
TI  - Can executive cognitive measures differentiate between patients with spinal- and
      bulbar-onset amyotrophic lateral sclerosis?
AB  - Although executive functions in sporadic non-demented amyotrophic lateral
      sclerosis (ALS) patients are mostly affected, it remains unclear whether
      executive measures can differentiate between patients with bulbar and spinal ALS
      forms. Thirty spinal and 18 bulbar-onset ALS patients (ALS-s and ALS-b,
      respectively) as well as 47 demographically related healthy controls were
      examined in executive processes (Trail Making Test-part B [TMT-(B-A)]; Stroop
      Neuropsychological Screening Test [SNST]; Similarities subtest of the Wechsler
      Adult Intelligence Scale [WAIS Similarities]; Wisconsin Card Sorting Test
      [WCST]). ALS subgroups were similar with regard to demographic characteristics
      and disease duration; yet, ALS-b showed greater disease severity compared with
      ALS-s patients (p = .006). Both ALS-s and ALS-b patients were significantly
      inferior to healthy controls on TMT-(B-A) (p < .001), SNST (p = .009 and p = .02,
      respectively) and WAIS Similarities (p = .031 and p = .021, respectively),
      whereas ALS-s performed significantly worse than controls on the WCST
      perseverative responses (p = .005). However, neuropsychological measures did not
      significantly differ between ALS subgroups (p > .05). Despite the fact that ALS-b
      patients may present greater disease severity, specific executive impairments
      that are present early in the course of ALS seems to be independent of the site
      of onset.

PMID- 22403770
TI  - Program completion of a web-based tailored lifestyle intervention for adults:
      differences between a sequential and a simultaneous approach.
AB  - BACKGROUND: Unhealthy lifestyle behaviors often co-occur and are related to
      chronic diseases. One effective method to change multiple lifestyle behaviors is
      web-based computer tailoring. Dropout from Internet interventions, however, is
      rather high, and it is challenging to retain participants in web-based tailored
      programs, especially programs targeting multiple behaviors. To date, it is
      unknown how much information people can handle in one session while taking part
      in a multiple behavior change intervention, which could be presented either
      sequentially (one behavior at a time) or simultaneously (all behaviors at once).
      OBJECTIVES: The first objective was to compare dropout rates of 2 computer
      tailored interventions: a sequential and a simultaneous strategy. The second
      objective was to assess which personal characteristics are associated with
      completion rates of the 2 interventions. METHODS: Using an RCT design,
      demographics, health status, physical activity, vegetable consumption, fruit
      consumption, alcohol intake, and smoking were self-assessed through web-based
      questionnaires among 3473 adults, recruited through Regional Health Authorities
      in the Netherlands in the autumn of 2009. First, a health risk appraisal was
      offered, indicating whether respondents were meeting the 5 national health
      guidelines. Second, psychosocial determinants of the lifestyle behaviors were
      assessed and personal advice was provided, about one or more lifestyle behaviors.
      RESULTS: Our findings indicate a high non-completion rate for both types of
      intervention (71.0%; n = 2167), with more incompletes in the simultaneous
      intervention (77.1%; n = 1169) than in the sequential intervention (65.0%; n =
      998). In both conditions, discontinuation was predicted by a lower age
      (sequential condition: OR = 1.04; P < .001; CI = 1.02-1.05; simultaneous
      condition: OR = 1.04; P < .001; CI = 1.02-1.05) and an unhealthy lifestyle
      (sequential condition: OR = 0.86; P = .01; CI = 0.76-0.97; simultaneous
      condition: OR = 0.49; P < .001; CI = 0.42-0.58). In the sequential intervention,
      being male (OR = 1.27; P = .04; CI = 1.01-1.59) also predicted dropout. When
      respondents failed to adhere to at least 2 of the guidelines, those receiving the
      simultaneous intervention were more inclined to drop out than were those
      receiving the sequential intervention. CONCLUSION: Possible reasons for the
      higher dropout rate in our simultaneous intervention may be the amount of time
      required and information overload. Strategies to optimize program completion as
      well as continued use of computer-tailored interventions should be studied. TRIAL
      REGISTRATION: Dutch Trial Register NTR2168.

PMID- 22403772
TI  - Tapering of the cervical spinal canal in patients with Chiari I malformations.
AB  - BACKGROUND AND PURPOSE: Upper cervical spinal canal dimension may have a role in
      abnormal CSF dynamics in patients with Chiari I malformation. We attempted to
      measure spinal canal tapering from anteroposterior spinal canal dimensions in
      patients with Chiari I. MATERIALS AND METHODS: Twenty-one patients with Chiari I
      malformation, including 12 with syringomyelia and 7 patients with IS were
      identified from a local registry. Age- and sex-matched control subjects with
      cervical spine MR imaging findings reported as normal were selected from the
      PACS. The anteroposterior diameter of the spinal canal was measured at C1-C7 on
      T2-weighted sagittal MR images. The taper ratio of the spinal canal was
      calculated with the regression line. Goodness of fit was calculated as R(2).
      Differences between patients with Chiari I and other patients were tested for
      significance with Kruskal-Wallis tests and multivariate analysis. RESULTS: Taper
      ratios averaged -0.6 +/- 0.3 mm/level in the patients with Chiari and syrinx, 
      0.4 +/- 0.2 mm/level (mean +/- 1 SD) in the patients with Chiari without syrinx,
      and -0.3 +/- 0.5 mm/level in the patients with IS; control groups had average
      taper ratios of -0.3 +/- 0.2 mm/level. Mean R(2) equaled 0.43. Taper ratios in
      patients with Chiari and syringomyelia differed significantly from those in the
      control group (P = .003). Taper ratios in the patients with Chiari without syrinx
      and in patients with IS did not differ significantly from their matched control
      groups (P = .60 and 0.76, respectively). CONCLUSIONS: Patients with Chiari I and
      a syrinx have steeper tapering of the upper cervical spinal canal than matched
      controls.

PMID- 22403773
TI  - Coiling for paraclinoid aneurysms: time to make way for flow diverters?
AB  - BACKGROUND AND PURPOSE: Paraclinoid aneurysms represent challenging lesions for
      which endovascular techniques have gained widespread application in their
      treatment. A new endovascular strategy, flow diversion, is gaining importance in
      the treatment of these aneurysms. Before embracing flow diversion in larger
      numbers of patients with paraclinoid aneurysms, it is important to know the
      safety and efficacy of "traditional" endovascular methods for these aneurysms. We
      review complications and outcomes of patients with unruptured paraclinoid
      aneurysms treated with coils, with or without balloon and stent assistance, over
      the past 12 years at our institution. MATERIALS AND METHODS: A retrospective
      review of 118 patients with 126 unruptured paraclinoid aneurysms, treated between
      1999 and 2010, was performed. Clinical records, endovascular reports,
      angiographic results, and clinical outcomes were reviewed and analyzed. RESULTS:
      Fifty-nine percent of aneurysms were carotid-ophthalmic, 27% were hypophyseal, 9%
      were posterior carotid wall, 3% were carotid cave, and 2% were transitional.
      Twenty-one percent of aneurysms were symptomatic, and 3% were recurrent aneurysms
      after previous treatment. Fifty (40%) were treated with balloon assistance and 18
      (14%) with stent assistance. Technical complications causing permanent morbidity
      occurred in 1 patient (0.8%), while early clinical complications causing
      transient morbidity occurred in 5 (4%) patients. Complete occlusion was achieved
      in 40% of aneurysms immediately after treatment and in 66 (62%) aneurysms during
      follow-up (mean 31.9 +/- 28.4 months). Recurrences occurred in 18 patients (17%)
      and 10 (9%) patients were retreated. Clinical outcome was good in 95% and poor in
      5% of the 107 patients with follow-up (mean 37.0 +/- 33.7 months). Only in 1
      patient was poor outcome related to the endovascular procedure. Transient
      ischemic attacks occurred in 4% of patients. No cases of rebleeding were observed
      during follow-up. CONCLUSIONS: Modern endovascular coil treatment of unruptured
      paraclinoid aneurysms appears safe, with satisfactory, although not ideal, rates
      of complete occlusion. The introduction of flow diverters will probably increase
      the rate of complete angiographic occlusion, but this must be achieved with low
      complication rates.

PMID- 22403774
TI  - High-resolution 3D-constructive interference in steady-state MR imaging and 3D
      time-of-flight MR angiography in neurovascular compression: a comparison between
      3T and 1.5T.
AB  - BACKGROUND AND PURPOSE: High-resolution MR imaging is useful for diagnosis and
      preoperative planning in patients with NVC. Because high-field MR imaging
      promises higher SNR and resolution, the aim of this study was to determine the
      value of high-resolution 3D-CISS and 3D-TOF MRA at 3T compared with 1.5T in
      patients with NVC. MATERIALS AND METHODS: Forty-seven patients with NVC,
      trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia were
      examined at 1.5T and 3T, including high-resolution 3D-CISS and 3D-TOF MRA
      sequences. Delineation of anatomic structures, overall image quality, severity of
      artifacts, visibility of NVC, and assessment of the SNR and CNR were compared
      between field strengths. RESULTS: SNR and CNR were significantly higher at 3T (P
      < .001). Significantly better anatomic conspicuity, including delineation of CNs,
      nerve branches, and assessment of small vessels, was obtained at 3T (P < .02).
      Severity of artifacts was significantly lower at 3T (P < .001). Consequently,
      overall image quality was significantly higher at 3T. NVC was significantly
      better delineated at 3T (P < .001). Six patients in whom NVC was not with
      certainty identifiable at 1.5T were correctly diagnosed at 3T. CONCLUSIONS:
      Patients with NVC may benefit from the higher resolution and greater sensitivity
      of 3T for preoperative assessment of NVC, and 3T may be of particular value when
      1.5T is equivocal.

PMID- 22403775
TI  - Peer review: past, present, and future.

PMID- 22403776
TI  - Superior hypophyseal artery aneurysms have the lowest recurrence rate with
      endovascular therapy.
AB  - BACKGROUND AND PURPOSE: Given the challenges posed by surgical clipping,
      endovascular techniques have been increasingly used to treat SHA aneurysms. The
      purpose of this study was to assess the safety and efficacy of endovascular
      techniques in the treatment of SHA aneurysms. MATERIALS AND METHODS: Medical
      charts and initial and follow-up angiograms were reviewed retrospectively for all
      patients treated with endovascular procedures at our institution between January
      2006 and February 2011. RESULTS: We identified 87 patients with SHA aneurysms who
      were treated with endovascular techniques. Of these patients, 79 were women and
      only 8 were men (90.8% female predominance). Thirty-five patients were treated
      with coil embolization; 45, with stent-assisted coiling; 4, with balloon-assisted
      coil embolization; and 3, with a flow-diversion technique. Minor complications
      occurred in 2 patients (2.2%). None of the patients had a major complication. The
      mortality and permanent morbidity rates related to the procedure were 0%. Imaging
      follow-up was available for 89.4% of patients (DSA in 65, MRA in 11 patients) at
      a mean time point of 10.4 months (range, 6-60 months). Of the 76 patients with
      available follow-up, 3 patients had a recurrence (3.9%) and only 1 required
      further intervention (1.3%). Stent-assisted coiling was associated with lower
      recurrence rates than simple coil embolization. CONCLUSIONS: SHA aneurysms have
      the lowest recurrence rate with endovascular treatment compared with aneurysms in
      other locations by using historical data. Because of its safety and efficacy,
      endovascular therapy should be considered the procedure of choice for the
      treatment of SHA aneurysms.

PMID- 22403777
TI  - Hyperintense vessel sign on fluid-attenuated inversion recovery MR imaging is
      reduced by gadolinium.
AB  - The HVS on FLAIR imaging is a useful marker of acute ischemic stroke. We
      investigated whether prior administration of gadolinium-based contrast hindered
      detection of this sign on images from subjects with acute nonlacunar ischemic
      stroke <4.5 hours after onset. Both blinded and comparative unblinded analyses
      showed significantly reduced HVS detection on postcontrast images. We suggest
      that assessment for this sign should be performed on images acquired prior to
      contrast administration.

PMID- 22403778
TI  - Vascular wall imaging of vulnerable atherosclerotic carotid plaques: current
      state of the art and potential future of endovascular optical coherence
      tomography.
AB  - As stroke is one of the leading causes of death and long-term morbidity
      worldwide, the research community has studied cardiac embolic sources, as well as
      vessel wall pathologies. For the latter, attention has been focused on defining
      morphologic tissue features associated with catastrophic events stemming from the
      carotid artery. Multiple noninvasive imaging modalities are currently being used
      to image and classify carotid atherosclerotic plaques, such as MR imaging, CT,
      and sonography, in an effort to provide clinically relevant predictive metrics
      for use in patient risk stratification and to define appropriate treatment
      options. This article compares and contrasts these existing clinical imaging
      modalities along with discussion of a new endovascular technique originally
      developed for cardiology, OCT, with which 3D comprehensive high-resolution images
      of the arterial wall can be acquired.

PMID- 22403779
TI  - Distribution of cortical benzodiazepine receptor binding in right-handed healthy
      humans: a voxel-based statistical analysis of iodine 123 iomazenil SPECT with
      partial volume correction.
AB  - BACKGROUND AND PURPOSE: CBR imaging is highly susceptible to a PVE produced by
      morphologic changes in the brain related to aging and brain laterality. We
      assessed the influence of PVE produced by regional age-related changes in gray
      matter volume on I-123 iomazenil SPECT and elucidated the age-related changes in
      human CBR binding by using PVE-corrected SPECT images. MATERIALS AND METHODS:
      Nineteen right-handed healthy volunteers (range, 25-82 years; mean, 55 +/- 21
      years) underwent MR imaging and quantitative I-123 iomazenil SPECT imaging. The
      influence of age-related changes in rGMC on SPECT images before PVE correction
      was assessed. PVE correction of the SPECT images was performed by using an MR
      imaging-based method. Voxel-based linear regression analyses of the PVE-corrected
      SPECT images were performed by using SPM5. RESULTS: The age-related reductions in
      rGMC and BP without PVE correction revealed a significant direct proportional
      correlation. Voxel-based statistical analysis with PVE correction showed no
      significant age-related changes in BP. CONCLUSIONS: PVE correction was
      indispensable for the analysis of I-123 iomazenil SPECT images. PVE-corrected
      quantitative I-123 iomazenil SPECT images revealed no age-related changes in CBR
      binding in right-handed healthy humans.

PMID- 22403780
TI  - Atypical diffusion-restricted lesion in 5-Fluorouracil encephalopathy.
AB  - Central nervous system toxicity of 5-FU could show various manifestations, such
      as decreased alertness, disorientation, and agitation. It is generally accepted
      that lesions of 5-FU encephalopathy are mainly in the deep cerebral white matter
      and corpus callosum on MR imaging. Here we describe a case of 5-FU encephalopathy
      in gastric cancer with an atypical reversible diffusion-restricted lesion on MR
      imaging, showing bilateral basal ganglia, thalami, and parasagittal frontal
      cortex involvement on diffusion and T2-weighted imaging.

PMID- 22403781
TI  - Clinical assessment of standard and generalized autocalibrating partially
      parallel acquisition diffusion imaging: effects of reduction factor and spatial
      resolution.
AB  - BACKGROUND AND PURPOSE: PI improves routine EPI-based DWI by enabling higher
      spatial resolution and reducing geometric distortion, though it remains unclear
      which of these is most important. We evaluated the relative contribution of these
      factors and assessed their ability to increase lesion conspicuity and diagnostic
      confidence by using a GRAPPA technique. MATERIALS AND METHODS: Four separate DWI
      scans were obtained at 1.5T in 48 patients with independent variation of in-plane
      spatial resolution (1.88 mm(2) versus 1.25 mm(2)) and/or reduction factor (R = 1
      versus R = 3). A neuroradiologist with access to clinical history and additional
      imaging sequences provided a reference standard diagnosis for each case. Three
      blinded neuroradiologists assessed scans for abnormalities and also evaluated
      multiple imaging-quality metrics by using a 5-point ordinal scale. Logistic
      regression was used to determine the impact of each factor on subjective image
      quality and confidence. RESULTS: Reference standard diagnoses in the patient
      cohort were acute ischemic stroke (n = 30), ischemic stroke with hemorrhagic
      conversion (n = 4), intraparenchymal hemorrhage (n = 9), or no acute lesion (n =
      5). While readers preferred both a higher reduction factor and a higher spatial
      resolution, the largest effect was due to an increased reduction factor (odds
      ratio, 47 +/- 16). Small lesions were more confidently discriminated from
      artifacts on R = 3 images. The diagnosis changed in 5 of 48 scans, always toward
      the reference standard reading and exclusively for posterior fossa lesions.
      CONCLUSIONS: PI improves DWI primarily by reducing geometric distortion rather
      than by increasing spatial resolution. This outcome leads to a more accurate and
      confident diagnosis of small lesions.

PMID- 22403782
TI  - A preliminary prediction model with MR plaque imaging to estimate risk for new
      ischemic brain lesions on diffusion-weighted imaging after endarterectomy or
      stenting in patients with carotid stenosis.
AB  - BACKGROUND AND PURPOSE: Findings on MR imaging of carotid plaques correlate with
      histologic findings and may be useful in identifying vulnerable plaques. The
      objective of this study was to show how MR imaging findings and clinical factors
      could be used to construct a preliminary model and a nomogram for predicting the
      risk of new ischemic lesions on DWI following CEA or  CAS. MATERIALS AND METHODS:
      One hundred four patients with carotid stenosis undergoing treatment (63 CEA, 41
      CAS) were prospectively enrolled (mean age, 71.7 +/- 7.0 years; 11 women). T1-SIR
      and T2-SIR of carotid plaque were measured on MR imaging. Associations among
      carotid MR imaging findings, treatment procedures, degree of stenosis,
      cardiovascular risk factors, and occurrence of new ischemic lesions on DWI 1 day
      after treatment were studied by multivariate logistic  regression. RESULTS: One
      stroke occurred after CAS (2.4%), and none after CEA. New DWI lesions after
      treatment were observed in 25 patients (24%). Our preliminary prediction model
      demonstrated that T1-SIR (OR [per 0.5 increase], 3.99; 95% CI, 2.18-7.31; P <
      .0001) and CAS (OR, 2.06; 95% CI, 1.01-4.24; P = .048 compared with CEA) were
      positively associated with new DWI lesions on posttreatment DWI scans. T2-SIR (OR
      [per 0.5 increase], 0.74; 95% CI, 0.55-0.98; P = .037) was negatively associated.
      The C-index of this model was 0.79 (95% CI, 0.69-0.89), which indicated some
      utility in predicting the  response. CONCLUSIONS: Our preliminary prediction
      model and nomogram may provide an individualized risk estimate of new ischemic
      lesions after CEA or CAS and useful information for decision-making regarding
      treatment  strategy.

PMID- 22403783
TI  - Delayed ipsilateral parenchymal hemorrhage following flow diversion for the
      treatment of anterior circulation aneurysms.
AB  - BACKGROUND AND PURPOSE: The PED is a flow-diverting stent designed for the
      treatment of cerebral aneurysms. We report 4 cases of delayed ipsilateral IPH
      following the technically successful treatment of anterior circulation aneurysms
      with the PED. MATERIALS AND METHODS: Clinical and imaging data from all patients
      undergoing aneurysm treatment with the PED at 2 institutions were analyzed to
      assess the incidence of delayed IPH after treatment with the PED. RESULTS: A
      total of 66 patients (47 anterior circulation) with cerebral aneurysms underwent
      treatment with a PED between January 2008 and November 2010. Four patients
      experienced delayed periprocedural IPH, all after the treatment of anterior
      circulation aneurysms (8.5%, 4/47). The aneurysm size ranged from 5 to 21 mm. All
      IPHs occurred within the cerebral hemisphere, ipsilateral to the treated
      aneurysm, and were anatomically remote from the treated aneurysms. All procedures
      were uncomplicated, and patients emerged from general anesthesia at neurologic
      baseline. The hemorrhages became clinically evident between 1 and 6 days after
      the procedure. Two patients had unfavorable outcomes (mRS scores, 4 and 6).
      CONCLUSIONS: Delayed IPH may occur after the treatment of anterior circulation
      aneurysms with flow diverters. This complication does not seem to be restricted
      to a specific aneurysm subtype and does not seem to be related to an
      intraprocedural complication or solely attributable to DAT.

PMID- 22403784
TI  - Interleukin-1beta-induced barrier dysfunction is signaled through PKC-theta in
      human brain microvascular endothelium.
AB  - Blood-brain barrier dysfunction is a serious consequence of inflammatory brain
      diseases, cerebral infections, and trauma. The proinflammatory cytokine
      interleukin (IL)-1beta is central to neuroinflammation and contributes to brain
      microvascular leakage and edema formation. Although it is well known that IL
      1beta exposure directly induces hyperpermeability in brain microvascular
      endothelium, the molecular mechanisms mediating this response are not completely
      understood. In the present study, we found that exposure of the human brain
      microvascular endothelium to IL-1beta triggered activation of novel PKC isoforms
      delta, MU, and theta, followed by decreased transendothelial electrical
      resistance (TER). The IL-1beta-induced decrease in TER was prevented by small
      hairpin RNA silencing of PKC-theta or by treatment with the isoform-selective PKC
      inhibitor Go6976 but not by PKC inhibitors that are selective for all PKC
      isoforms other than PKC-theta. Decreased TER coincided with increased
      phosphorylation of regulatory myosin light chain and with increased proapoptotic
      signaling indicated by decreased uptake of mitotracker red in response to IL
      1beta treatment. However, neither of these observed effects were prevented by
      Go6976 treatment, indicating lack of causality with respect to decreased TER.
      Instead, our data indicated that the mechanism of decreased TER involves PKC
      theta-dependent phosphorylation of the tight junction protein zona occludens (ZO)
      1. Because IL-1beta is a central inflammatory mediator, our interpretation is
      that inhibition of PKC-theta or inhibition of ZO-1 phosphorylation could be
      viable strategies for preventing blood-brain barrier dysfunction under a variety
      of neuroinflammatory conditions.

PMID- 22403785
TI  - Functional Cftr in crypt epithelium of organotypic enteroid cultures from murine
      small intestine.
AB  - Physiological studies of intact crypt epithelium have been limited by problems of
      accessibility in vivo and dedifferentiation in standard primary culture.
      Investigations of murine intestinal stem cells have recently yielded a primary
      intestinal culture in three-dimensional gel suspension that recapitulates crypt
      structure and epithelial differentiation (Sato T, Vries RG, Snippert HJ, van de
      Wetering M, Barker N, Stange DE, Van Es JH, Abo A, Kujala P, Peters PJ, Clevers
      H. Nature 459: 262-265, 2009). We investigated the utility of murine intestinal
      crypt cultures (termed "enteroids") for physiological studies of crypt epithelium
      by focusing on the transport activity of the cystic fibrosis transmembrane
      conductance regulator Cftr. Enteroids had multiple crypts with well
      differentiated goblet and Paneth cells that degranulated on exposure to the
      muscarinic agonist carbachol. Modified growth medium provided a crypt
      proliferation rate, as measured by 5-ethynyl-2'-deoxyuridine labeling, which was
      similar to proliferation in vivo. Immunoblots demonstrated equivalent Cftr
      expression in comparisons of freshly isolated crypts with primary and passage 1
      enteroids. Apparent enteroid differences in mRNA expression of other transporters
      were primarily associated with villous epithelial contamination of freshly
      isolated crypts. Microelectrode analysis revealed cAMP-stimulated membrane
      depolarization in enteroid epithelium from wild-type (WT) but not Cftr knockout
      (KO) mice. Morphological and microfluorimetric studies, respectively,
      demonstrated Cftr-dependent cell shrinkage and lower intracellular pH in WT
      enteroid epithelium in contrast to Cftr KO epithelium or WT epithelium treated
      with Cftr inhibitor 172. We conclude that crypt epithelium of murine enteroids
      exhibit Cftr expression and activity that recapitulates crypt epithelium in vivo.
      Enteroids provide a primary culture model that is suitable for physiological
      studies of regenerating crypt epithelium.

PMID- 22403786
TI  - Transport, cilia, and PKD: must we in (cyst) on interrelationships? Focus on
      "Increased Na+/H+ exchanger activity on the apical surface of a cilium-deficient
      cortical collecting duct principal cell model of polycystic kidney disease".

PMID- 22403787
TI  - Chronic nicotine induces hypoxia inducible factor-2alpha in perinatal rat adrenal
      chromaffin cells: role in transcriptional upregulation of KATP channel subunit
      Kir6.2.
AB  - Fetal nicotine exposure causes impaired adrenal catecholamine secretion and
      increased neonatal mortality during acute hypoxic challenges. Both effects are
      attributable to upregulation of ATP-sensitive K(+) channels (K(ATP) channels) and
      can be rescued by pretreatment with the blocker, glibenclamide. Although use of
      in vitro models of primary and immortalized, fetal-derived rat adrenomedullary
      chromaffin cells (i.e., MAH cells) demonstrated the involvement of alpha7
      nicotinic ACh receptor (nAChR) stimulation and the transcription factor, HIF
      2alpha, the latter's role was unclear. Using Western blots, we show that chronic
      nicotine causes a progressive, time-dependent induction of HIF-2alpha in MAH
      cells that parallels the upregulation of K(ATP) channel subunit, Kir6.2.
      Moreover, a common HIF target, VEGF mRNA, was also upregulated after chronic
      nicotine. All the above effects were prevented during co-incubation with alpha
      bungarotoxin (100 nM), a specific alpha7 nAChR blocker, and were absent in HIF
      2alpha-deficient MAH cells. Chromatin immunoprecipitation (ChIP) assays
      demonstrated binding of HIF-2alpha to a putative hypoxia response element in
      Kir6.2 gene promoter. Specificity of this signaling pathway was validated in
      adrenal glands from pups born to dams exposed to nicotine throughout gestation;
      the upregulation of both HIF-2alpha and Kir6.2 was confined to medullary, but not
      cortical, tissue. This study has uncovered a signaling pathway whereby a
      nonhypoxic stimulus (nicotine) promotes HIF-2alpha-mediated transcriptional
      upregulation of a novel target, Kir6.2 subunit. The data suggest that the HIF
      pathway may be involved in K(ATP) channel-mediated neuroprotection during brain
      ischemia, and in the effects of chronic nicotine on ubiquitous brain alpha7
      nAChR.

PMID- 22403788
TI  - Mechanical loading induces the expression of a Pol I regulon at the onset of
      skeletal muscle hypertrophy.
AB  - The main goal of the present study was to investigate the regulation of ribosomal
      DNA (rDNA) gene transcription at the onset of skeletal muscle hypertrophy. Mice
      were subjected to functional overload of the plantaris by bilateral removal of
      the synergist muscles. Mechanical loading resulted in muscle hypertrophy with an
      increase in rRNA content. rDNA transcription, as determined by 45S pre-rRNA
      abundance, paralleled the increase in rRNA content and was consistent with the
      onset of the hypertrophic response. Increased transcription and protein
      expression of c-Myc and its downstream polymerase I (Pol I) regulon (POL1RB, TIF
      1A, PAF53, TTF1, TAF1C) was also consistent with the increase in rRNA. Similarly,
      factors involved in rDNA transcription, such as the upstream binding factor and
      the Williams syndrome transcription factor, were induced by mechanical loading in
      a corresponding temporal fashion. Chromatin immunoprecipitation revealed that
      these factors, together with Pol I, were enriched at the rDNA promoter. This, in
      addition to an increase in histone H3 lysine 9 acetylation, demonstrates that
      mechanical loading regulates rRNA synthesis by inducing a gene expression program
      consisting of a Pol I regulon, together with accessory factors involved in
      transcription and chromatin remodeling at the rDNA promoter. Altogether, these
      data indicate that transcriptional and epigenetic mechanisms take place in the
      regulation of ribosome production at the onset of muscle hypertrophy.

PMID- 22403789
TI  - Effect of insulin and contraction on glycogen synthase phosphorylation and
      kinetic properties in epitrochlearis muscles from lean and obese Zucker rats.
AB  - In the present study, the effects of insulin and contraction on glycogen synthase
      (GS) kinetic properties and phosphorylation were investigated in epitrochlearis
      muscles from lean and obese Zucker rats. Total GS activity and protein expression
      were ~15% lower in epitrochlearis from obese rats compared with lean rats.
      Insulin-stimulated GS fractional activity and affinity for UDP-glucose were lower
      (higher K(m)) in muscles from obese rats. GS Ser(641) and Ser(645,649,653,657)
      phosphorylation was higher in insulin-stimulated muscles from obese rats, which
      agreed with lower GS activation. Contraction-mediated GS dephosphorylation of
      Ser(641), Ser(641+645), Ser(645,649,653,657), and Ser(7+10) was normal in muscles
      from obese Zucker rats, and GS fractional activity increased to similar levels in
      epitrochlearis muscles from lean and obese rats. GS affinity for UDP glucose was
      ~0.8, ~0.4, and ~0.1 mM with assay buffers containing 0, 0.17, and 12 mM glucose
      6-phosphate, respectively. Contraction increased affinity for UDP-glucose
      (reduced K(m)) at a physiological concentration of glucose 6-phosphate (0.17 mM)
      to ~0.2 mM in muscles from both lean and obese rats. Interestingly, in the
      absence of glucose 6-phosphate in the assay buffer, contraction (and insulin) did
      not influence GS affinity for UDP-glucose, indicating that affinity is regulated
      by sensitivity for glucose 6-phosphate. In conclusion, contraction-mediated
      activation and dephosphorylation of GS were normal in muscles from obese Zucker
      rats, whereas insulin-mediated GS activation and dephosphorylation were impaired.

PMID- 22403790
TI  - The role of the superior laryngeal nerve in esophageal reflexes.
AB  - The aim of this study was to determine the role of the superior laryngeal nerve
      (SLN) in the following esophageal reflexes: esophago-upper esophageal sphincter
      (UES) contractile reflex (EUCR), esophago-lower esophageal sphincter (LES)
      relaxation reflex (ELIR), secondary peristalsis, pharyngeal swallowing, and
      belch. Cats (N = 43) were decerebrated and instrumented to record EMG of the
      cricopharyngeus, thyrohyoideus, geniohyoideus, and cricothyroideus; esophageal
      pressure; and motility of LES. Reflexes were activated by stimulation of the
      esophagus via slow balloon or rapid air distension at 1 to 16 cm distal to the
      UES. Slow balloon distension consistently activated EUCR and ELIR from all areas
      of the esophagus, but the distal esophagus was more sensitive than the proximal
      esophagus. Transection of SLN or proximal recurrent laryngeal nerves (RLN)
      blocked EUCR and ELIR generated from the cervical esophagus. Distal RLN
      transection blocked EUCR from the distal cervical esophagus. Slow distension of
      all areas of the esophagus except the most proximal few centimeters activated
      secondary peristalsis, and SLN transection had no effect on secondary
      peristalsis. Slow distension of all areas of the esophagus inconsistently
      activated pharyngeal swallows, and SLN transection blocked generation of
      pharyngeal swallows from all levels of the esophagus. Slow distension of the
      esophagus inconsistently activated belching, but rapid air distension
      consistently activated belching from all areas of the esophagus. SLN transection
      did not block initiation of belch but blocked one aspect of belch, i.e.,
      inhibition of cricopharyngeus EMG. Vagotomy blocked all aspects of belch
      generated from all areas of esophagus and blocked all responses of all reflexes
      not blocked by SLN or RLN transection. In conclusion, the SLN mediates all
      aspects of the pharyngeal swallow, no portion of the secondary peristalsis, and
      the EUCR and ELIR generated from the proximal esophagus. Considering that SLN is
      not a motor nerve for any of these reflexes, the role of the SLN in control of
      these reflexes is sensory in nature only.

PMID- 22403792
TI  - Effects of the combined administration of propranolol plus sorafenib on portal
      hypertension in cirrhotic rats.
AB  - Low doses of sorafenib have been shown to decrease portal pressure (PP), portal
      systemic shunts, and liver fibrosis in cirrhotic rats. Nonselective beta blockers
      (NSBB) are the only drugs recommended for the treatment of portal hypertension.
      The aim of our study was to explore whether the combination of propranolol and
      sorafenib might show an additive effect reducing PP in cirrhotic rats. Groups of
      common bile duct-ligated cirrhotic rats (CBDL) and sham-operated control rats
      were treated by gavage with vehicle, propranolol (30 mg.kg(-1).day(-1)),
      sorafenib (1 mg.kg(-1).day(-1)), or propranolol+sorafenib. Treatment began 2 wk
      after the CBDL or sham operation. Hemodynamic evaluation was performed after 2 wk
      of treatment. In cirrhotic rats, propranolol and sorafenib produced a significant
      (P < 0.001) and similar reduction in PP (-19 and -15%, respectively). This was
      achieved through different mechanisms: whereas propranolol decreased PP by
      reducing portal blood flow (-35%; P = 0.03), sorafenib decreased PP without
      decreasing portal flow indicating decreased hepatic resistance. After
      propranolol+sorafenib, the fall in PP was significantly greater (-30%; P < 0.001)
      than with either drug alone, demonstrating an additive effect. However, the
      reduction in portal flow (-39%) under combined therapy was not significantly
      greater than after propranolol alone. Sorafenib, alone or in combination with
      propranolol, produced significant reduction in portal-systemic shunting (-25 and 
      33%, respectively), splanchnic vascularization (-37 and -41%, respectively),
      liver fibrosis (38%), and hepatic neovascularization (-42 and -51%,
      respectively). These effects were not observed after propranolol alone. In
      conclusion, the combination of propranolol+sorafenib causes a greater reduction
      in PP than either drug alone and decreases markedly the extent of portal-systemic
      shunting, splanchnic and hepatic neovascularization, and liver fibrosis,
      suggesting that this drug combination is a potentially useful strategy in the
      treatment of portal hypertension.

PMID- 22403791
TI  - Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Neural and
      neuro-immune mechanisms of visceral hypersensitivity in irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is characterized as functional because a
      pathobiological cause is not readily apparent. Considerable evidence, however,
      documents that sensitizing proinflammatory and lipotoxic lipids, mast cells and
      their products, tryptases, enteroendocrine cells, and mononuclear phagocytes and
      their receptors are increased in tissues of IBS patients with colorectal
      hypersensitivity. It is also clear from recordings in animals of the colorectal
      afferent innervation that afferents exhibit long-term changes in models of
      persistent colorectal hypersensitivity. Such changes in afferent excitability and
      responses to mechanical stimuli are consistent with relief of discomfort and pain
      in IBS patients, including relief of referred abdominal hypersensitivity, upon
      intra-rectal instillation of local anesthetic. In the aggregate, these
      experimental outcomes establish the importance of afferent drive in IBS,
      consistent with a larger literature with respect to other chronic conditions in
      which pain is a principal complaint (e.g., neuropathic pain, painful bladder
      syndrome, fibromyalgia). Accordingly, colorectal afferents and the environment in
      which these receptive endings reside constitute the focus of this review. That
      environment includes understudied and incompletely understood contributions from
      immune-competent cells resident in and recruited into the colorectum. We close
      this review by highlighting deficiencies in existing knowledge and identifying
      several areas for further investigation, resolution of which we anticipate would
      significantly advance our understanding of neural and neuro-immune contributions
      to IBS pain and hypersensitivity.

PMID- 22403793
TI  - Enteropathogenic Escherichia coli inhibits ileal sodium-dependent bile acid
      transporter ASBT.
AB  - Apical sodium-dependent bile acid transporter (ASBT) is responsible for the
      absorption of bile acids from the intestine. A decrease in ASBT function and
      expression has been implicated in diarrhea associated with intestinal
      inflammation. Whether infection with pathogenic microorganisms such as the
      enteropathogenic Escherichia coli (EPEC) affect ASBT activity is not known. EPEC
      is a food-borne enteric pathogen that translocates bacterial effector molecules
      via type three secretion system (TTSS) into host cells and is a major cause of
      infantile diarrhea. We investigated the effects of EPEC infection on ileal ASBT
      function utilizing human intestinal Caco2 cells and HEK-293 cells stably
      transfected with ASBT-V5 fusion protein (2BT cells). ASBT activity was
      significantly inhibited following 60 min infection with EPEC but not with
      nonpathogenic E. coli. Mutations in bacterial escN, espA, espB, and espD, the
      genes encoding for the elements of bacterial TTSS, ablated EPEC inhibitory effect
      on ASBT function. Furthermore, mutation in the bacterial BFP gene encoding for
      bundle-forming pili abrogated the inhibition of ASBT by EPEC, indicating the
      essential role for bacterial aggregation and the early attachment. The inhibition
      by EPEC was associated with a significant decrease in the V(max) of the
      transporter and a reduction in the level of ASBT on the plasma membrane. The
      inhibition of ASBT by EPEC was blocked in the presence of protein tyrosine
      phosphatase inhibitors. Our studies provide novel evidence for the alterations in
      the activity of ASBT by EPEC infection and suggest a possible effect for EPEC in
      influencing intestinal bile acid homeostasis.

PMID- 22403794
TI  - Site-specific regulation of ion transport by prolactin in rat colon epithelium.
AB  - The effect of prolactin (PRL) on ion transport across the rat colon epithelium
      was investigated using Ussing chamber technique. PRL (1 MUg/ml) induced a
      sustained decrease in short-circuit current (I(sc)) in the distal colon with an
      EC(50) value of 100 ng/ml and increased I(sc) in the proximal colon with an
      EC(50) value of 49 ng/ml. In the distal colon, the PRL-induced decrease in I(sc)
      was not affected by Na(+) channel blocker amiloride or Cl(-) channel blockers,
      NPPB, DPC, or DIDS, added mucosally. However, the response was inhibited by
      mucosal application of K(+) channel blockers glibenclamide, quinidine, and
      chromanol 293B, whereas other K(+) channel blockers, Ba(2+), tetraethylammonium,
      clotrimazole, and apamin, failed to have effects. The PRL-induced decrease in
      I(sc) was also inhibited by Na(+)-K(+)-2Cl(-) transporter inhibitor bumetanide,
      Ba(2+), and chromanol 293B applied serosally. In the transverse and proximal
      colon, the PRL-induced increase in I(sc) was suppressed by DPC, glibenclamide,
      and bumetanide, but not by NPPB, DIDS, or amiloride. The PRL-induced changes in
      I(sc) in both distal and proximal colon were abolished by JAK2 inhibitor AG490,
      but not BAPTA-AM, the Ca(2+) chelating agent, or phosphatidylinositol 3-kinase
      inhibitor wortmannin. These results suggest a segment-specific effect of PRL in
      rat colon, by activation of K(+) secretion in the distal colon and activation of
      Cl(-) secretion in the transverse and proximal colon. Both PRL actions are
      mediated by JAK-STAT-dependent pathway, but not phosphatidylinositol 3-kinase
      pathway or Ca(2+) mobilization. These findings suggest a role of PRL in the
      regulation of electrolyte transport in mammalian colon.

PMID- 22403796
TI  - Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil
      induced intestinal mucositis in mice.
AB  - Although NADPH oxidase 1 (NOX1) has been shown to be highly expressed in the
      gastrointestinal tract, the physiological and pathophysiological roles of this
      enzyme are not yet fully understood. In the present study, we investigated the
      role of NOX1 in the pathogenesis of intestinal mucositis induced by the cancer
      chemotherapeutic agent 5-fluorouracil (5-FU) in mice. Intestinal mucositis was
      induced in Nox1 knockout (Nox1KO) and littermate wild-type (WT) mice via single,
      daily administration of 5-FU for 5 days. In WT mice, 5-FU caused severe
      intestinal mucositis characterized by a shortening of villus height, a disruption
      of crypts, a loss of body weight, and diarrhea. In Nox1KO mice, however, the
      severity of mucositis was significantly reduced, particularly with respect to
      crypt disruption. The numbers of apoptotic caspase-3- and caspase-8-activated
      cells in the intestinal crypt increased 24 h after the first 5-FU administration
      but were overall significantly lower in Nox1KO than in WT mice. Furthermore, the
      5-FU-mediated upregulation of TNF-alpha, IL-1beta, and NOX1 and the production of
      reactive oxygen species were significantly attenuated in Nox1KO mice compared
      with that in WT mice. These findings suggest that NOX1 plays an important role in
      the pathogenesis of 5-FU-induced intestinal mucositis. NOX1-derived ROS
      production following administration of 5-FU may promote the apoptotic response
      through upregulation of inflammatory cytokines.

PMID- 22403795
TI  - Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Genetic
      epidemiology and pharmacogenetics in irritable bowel syndrome.
AB  - The objectives of this review are twofold. Our first objective is to evaluate the
      evidence supporting a role for genetics in irritable bowel syndrome (IBS).
      Specific examples of the associations of genetic variation and symptoms,
      syndromes, and intermediate phenotypes, including neurotransmitter (serotonergic,
      alpha(2)-adrenergic, and cannabinoid) mechanisms, inflammatory pathways (IL-10,
      TNFalpha, GNbeta3, and susceptibility loci involved in Crohn's disease), and bile
      acid metabolism, are explored. The second objective is to review pharmacogenetics
      in IBS, with the focus on cytochrome P-450 metabolism of drugs used in IBS,
      modulation of motor and sensory responses to serotonergic agents based on the 5
      hydroxytryptamine (5-HT) transporter-linked polymorphic region (5-HTTLPR) and 5
      HT(3) genetic variants, responses to a nonselective cannabinoid agonist
      (dronabinol) based on cannabinoid receptor (CNR1) and fatty acid amide hydrolase
      (FAAH) variation, and responses to a bile acid (sodium chenodeoxycholate) and
      bile acid binding (colesevelam) based on klothobeta (KLB) and fibroblast growth
      factor receptor 4 (FGFR4) variation. Overall, there is limited evidence of a
      genetic association with IBS; the most frequently studied association is with 5
      HTTLPR, and the most replicated association is with TNF superfamily member 15.
      Most of the pharmacogenetic associations are reported with intermediate
      phenotypes in relatively small trials, and confirmation in large clinical trials
      using validated clinical end points is still required. No published genome-wide
      association studies in functional gastrointestinal or motility disorders have
      been published.

PMID- 22403797
TI  - Impact of salt on cardiac differential gene expression and coronary lesion in
      normotensive mineralocorticoid-treated mice.
AB  - We previously reported that excess of deoxycorticosterone-acetate (DOCA)/salt
      induced cardiac hypertrophy in the absence of hypertension in one-renin gene
      mice. This model allows us to study molecular mechanisms of high-salt intake in
      the development of cardiovascular remodeling, independently of blood pressure in
      a high mineralocorticoid state. In this study, we compared the effect of 5-wk low
      and high-salt intake on cardiovascular remodeling and cardiac differential gene
      expression in mice receiving the same amount of DOCA. Differential gene and
      protein expression was measured by high-density cDNA microarray assays, real-time
      PCR and Western blot analysis in DOCA-high salt (HS) vs. DOCA-low salt (LS) mice.
      DOCA-HS mice developed cardiac hypertrophy, coronary perivascular fibrosis, and
      left ventricular dysfunction. Differential gene and protein expression
      demonstrated that high-salt intake upregulated a subset of genes encoding for
      proteins involved in inflammation and extracellular matrix remodeling (e.g.,
      Col3a1, Col1a2, Hmox1, and Lcn2). A major subset of downregulated genes encoded
      for transcription factors, including myeloid differentiation primary response
      (MyD) genes. Our data provide some evidence that vascular remodeling, fibrosis,
      and inflammation are important consequences of a high-salt intake in DOCA mice.
      Our study suggests that among the different pathogenic factors of cardiac and
      vascular remodeling, such as hypertension and mineralocorticoid excess and sodium
      intake, the latter is critical for the development of the profibrotic and
      proinflammatory phenotype observed in the heart of normotensive DOCA-treated
      mice.

PMID- 22403798
TI  - Hypoxia activates nucleus tractus solitarii neurons projecting to the
      paraventricular nucleus of the hypothalamus.
AB  - Peripheral chemoreceptor afferent information is sent to the nucleus tractus
      solitarii (nTS), integrated, and relayed to other brain regions to alter
      cardiorespiratory function. The nTS projects to the hypothalamic paraventricular
      nucleus (PVN), but activation and phenotype of these projections during
      chemoreflex stimulation is unknown. We hypothesized that activation of PVN
      projecting nTS neurons occurs primarily at high intensities of hypoxia. We
      assessed ventilation and cardiovascular parameters in response to increasing
      severities of hypoxia. Retrograde tracers were used to label nTS PVN-projecting
      neurons and, in some rats, rostral ventrolateral medulla (RVLM)-projecting
      neurons. Immunohistochemistry was performed to identify nTS cells that were
      activated (Fos-immunoreactive, Fos-IR), catecholaminergic, and GABAergic
      following hypoxia. Conscious rats underwent 3 h normoxia (n = 4, 21% O(2)) or
      acute hypoxia (12, 10, or 8% O(2); n = 5 each). Hypoxia increased ventilation and
      the number of Fos-IR nTS cells (21%, 13 +/- 2; 12%, 58 +/- 4; 10%, 166 +/- 22;
      8%, 186 +/- 6). Fos expression after 10% O(2) was similar whether arterial
      pressure was allowed to decrease (-13 +/- 1 mmHg) or was held constant. The
      percentage of PVN-projecting cells activated was intensity dependent, but
      contrary to our hypothesis, PVN-projecting nTS cells exhibiting Fos-IR were found
      at all hypoxic intensities. Notably, at all intensities of hypoxia, ~75% of the
      activated PVN-projecting nTS neurons were catecholaminergic. Compared with RVLM
      projecting cells, a greater percentage of PVN-projecting nTS cells was activated
      by 10% O(2). Data suggest that increasing hypoxic intensity activates nTS PVN
      projecting cells, especially catecholaminergic, PVN-projecting neurons. The nTS
      to PVN catecholaminergic pathway may be critical even at lower levels of
      chemoreflex activation and more important to cardiorespiratory responses than
      previously considered.

PMID- 22403799
TI  - Normal lactational environment restores cardiomyocyte number after uteroplacental
      insufficiency: implications for the preterm neonate.
AB  - A reduced complement of cardiomyocytes in early life can adversely affect life
      long cardiac functional reserve. In the present study, using a cross-fostering
      approach in rats, we examined the contributions of the prenatal and postnatal
      environments in the programming of cardiomyocyte growth. Rat dams underwent
      either bilateral uterine vessel ligation (Restricted) or sham surgery (Control)
      on day 18 of gestation. One day after birth, Control and Restricted pups were
      cross-fostered onto Control (normal lactation) or Restricted (impaired lactation
      due to impaired mammary gland formation) mothers. In male offspring, genes
      involved in cardiomyocyte differentiation, proliferation, hypertrophy and
      apoptosis were examined at gestational day 20 and postnatal days 1 and 7 to
      assess effects on cardiomyocyte growth. At postnatal day 7 cardiomyocyte number
      was determined stereologically. Offspring were examined at age 6 mo for evidence
      of hypertension and pathological cardiac gene expression. There was an increase
      in Igf1 and Igf2 mRNA expression in hearts of Restricted pups at gestational day
      20. At postnatal day 7, Agtr1a and Agtr1b mRNA expression as well as Bcl2 and
      Cmyc were elevated in all hearts from offspring that were prenatally or
      postnatally growth restricted. There was a significant reduction (-29%) in
      cardiomyocyte number in the Restricted-on-Restricted group. Importantly, this
      deficit was prevented by optimization of postnatal nutrition (in the Restricted
      on-Control group). At 6 mo, blood pressure was significantly elevated in the
      Restricted-on-Restricted group, but there was no difference in expression of the
      cardiac hypertrophy, remodeling or angiogenic genes across groups. In conclusion,
      the findings reveal a critical developmental window, when cardiomyocytes are
      still proliferating, whereby improved neonatal nutrition has the capacity to
      restore cardiomyocyte number to normal levels. These findings are of particular
      relevance to the preterm infant who is born at a time when cardiomyocytes are
      immature and still dividing.

PMID- 22403800
TI  - Airway smooth muscle hypertrophy and hyperplasia in asthma.
AB  - RATIONALE: Increased thickness of the airway smooth muscle (ASM) layer in asthma
      may result from hyperplasia or hypertrophy of muscle cells or increased
      extracellular matrix (ECM). OBJECTIVES: To relate ASM hypertrophy, ASM
      hyperplasia, and deposition of ECM to the severity and duration of asthma.
      METHODS: Airways from control subjects (n = 51) and from cases of nonfatal (n =
      49) and fatal (n = 55) asthma were examined postmortem. Mean ASM cell volume
      (V(C)), the number of ASM cells per length of airway (N(L)), and the volume
      fraction of extracellular matrix (f(ECM)) within the ASM layer were estimated.
      Comparisons between subject groups were made on the basis of general linear
      regression models. MEASUREMENTS AND MAIN RESULTS: Mean V(C) was increased in the
      large airways of cases of nonfatal asthma (P = 0.015) and fatal asthma (P <
      0.001) compared with control subjects. N(L) was similar in nonfatal cases and
      control subjects but increased in large (P < 0.001), medium (P < 0.001), and
      small (P = 0.034) airways of cases of fatal asthma compared with control subjects
      and with nonfatal cases (large and medium airways, P <= 0.003). The f(ECM) was
      similar in cases of asthma and control subjects. Duration of asthma was
      associated with a small increase in N(L). CONCLUSIONS: Hypertrophy of ASM cells
      occurs in the large airways in both nonfatal and fatal cases of asthma, but
      hyperplasia of ASM cells is present in the large and small airways in fatal
      asthma cases only. Both are associated with an absolute increase in ECM. Duration
      of asthma has little or no effect on ASM hypertrophy or hyperplasia or f(ECM).

PMID- 22403801
TI  - Chest computed tomography scores are predictive of survival in patients with
      cystic fibrosis awaiting lung transplantation.
AB  - RATIONALE: Up to one-third of patients with cystic fibrosis (CF) awaiting lung
      transplantation (LTX) die while waiting. Inclusion of computed tomography (CT)
      scores may improve survival prediction models such as the lung allocation score
      (LAS). OBJECTIVES: This study investigated the association between CT and
      survival in patients with CF screened for LTX. METHODS: Clinical data and chest
      CTs of 411 patients with CF screened for LTX between 1990 and 2005 were collected
      from 17 centers. CTs were scored with the Severe Advanced Lung Disease (SALD)
      four-category scoring system, including the components infection/inflammation
      (INF), air trapping/hypoperfusion (AT), normal/hyperperfusion (NOR), and
      bulla/cysts (BUL). The volume of each component was computed using semiautomated
      software. Survival analysis included Kaplan-Meier curves and Cox regression
      models. MEASUREMENTS AND MAIN RESULTS: Three hundred and sixty-six (186 males) of
      411 patients entered the waiting list (median age, 23 yr; range, 5-58 yr).
      Subsequently, 67 of 366 (18%) died while waiting, 263 of 366 (72%) underwent LTX,
      and 36 of 366 (10%) were awaiting LTX at the census date. INF and LAS were
      significantly associated with waiting list mortality in univariate analyses. The
      multivariate Cox model including INF and LAS grouped in tertiles, and comparing
      tertiles 2 and 3 with tertile 1, showed waiting list mortality hazard ratios of
      1.62 (95% confidence interval [95% CI], 0.78-3.36; P = 0.19) and 2.65 (95% CI,
      1.35-5.20; P = 0.005) for INF, and 1.42 (95% CI, 0.63-3.24; P = 0.40), and 2.32
      (95% CI, 1.17-4.60; P = 0.016) for LAS, respectively. These results indicated
      that INF and LAS had significant, independent predictive value for survival.
      CONCLUSIONS: CT score INF correlates with survival, and adds to the predictive
      value of LAS.

PMID- 22403802
TI  - Immune responses in cystic fibrosis: are they intrinsically defective?
AB  - Cystic fibrosis (CF), the most common lethal single-gene disorder affecting
      Northern Europeans and North Americans, is caused by mutations in the cystic
      fibrosis transmembrane conductance regulator (CFTR) gene. Cftr is a chloride
      channel and a regulator of other ion channels, and many aspects of the CF
      phenotype are directly related to ion channel abnormalities attributable to CFTR
      mutation. Lung disease is the most common limitation to the quantity and quality
      of life for patients with CF. One aspect that continues to be enigmatic is the
      observed alterations in innate and adaptive immune responses to certain
      pathogens. Altered responses to Pseudomonas aeruginosa and Aspergillus fumigatus,
      with an increase in neutrophil chemoattractants in the former case and a hyper
      IgE-like state in the latter, are common in CF. Several lines of evidence suggest
      that the proinflammatory cytokine response to bacterial infection is exaggerated
      in CF. A literature search reveals that, although the abnormalities in CF immune
      cells have been recognized since the 1970s, few studies until recently have
      appreciated the role that CFTR plays in these cell types. A growing body of
      evidence has emerged that points to neutrophils, macrophages, and T cells as
      being central to the infectious and pulmonary pathology, accounting for the
      majority of CF mortality. Primary CFTR defects in T cells are providing new
      insights into the misorchestration of the CF immune system due to aberrant
      signaling pathways. Defective CFTR function disrupts the balance of intracellular
      ion concentrations, including [Ca(2+)], which is known to drive gene expression
      pathways. New evidence links this hypothesis to anomalies in immune activation
      observed across CF cell types, which could shed light on the inability of
      individuals with CF to effectively clear pathogens. This review focuses on the
      emerging role of Cftr in gene expression and other functions in cells of the
      innate and adaptive immune system.

PMID- 22403803
TI  - AGR2 is induced in asthma and promotes allergen-induced mucin overproduction.
AB  - Mucins are gel-forming proteins that are responsible for the characteristic
      viscoelastic properties of mucus. Mucin overproduction is a hallmark of asthma,
      but the cellular requirements for airway mucin production are poorly understood.
      The endoplasmic reticulum (ER) protein anterior gradient homolog 2 (AGR2) is
      required for production of the intestinal mucin MUC2, but its role in the
      production of the airway mucins MUC5AC and MUC5B is not established. Microarray
      data were analyzed to examine the relationship between AGR2 and MUC5AC expression
      in asthma. Immunofluorescence was used to localize AGR2 in airway cells.
      Coimmunoprecipitation was used to identify AGR2-immature MUC5AC complexes. Agr2(
      /-) mice were used to determine the role of AGR2 in allergic airway disease. AGR2
      localized to the ER of MUC5AC- and MUC5B-producing airway cells and formed a
      complex with immature MUC5AC. AGR2 expression increased together with MUC5AC
      expression in airway epithelium from "Th2-high" asthmatics. Allergen-challenged
      Agr2(-/-) mice had greater than 50% reductions in MUC5AC and MUC5B proteins
      compared with allergen-challenged wild-type mice. Impaired mucin production in
      Agr2(-/-) mice was accompanied by an increase in the proportion of mucins
      contained within the ER and by evidence of ER stress in airway epithelium. This
      study shows that AGR2 increases with mucin overproduction in individuals with
      asthma and in mouse models of allergic airway disease. AGR2 interacts with
      immature mucin in the ER and loss of AGR2 impairs allergen-induced MUC5AC and
      MUC5B overproduction.

PMID- 22403804
TI  - A novel prostacyclin agonist protects against airway hyperresponsiveness and
      remodeling in mice.
AB  - Airway remodeling in bronchial asthma results from chronic, persistent airway
      inflammation. The effects of the reversal of airway remodeling by drug
      interventions remain to be elucidated. We investigated the effects of ONO-1301, a
      novel prostacyclin agonist with thromboxane inhibitory activity, on the
      prevention and reversibility of airway remodeling in an experimental chronic
      asthma model. Mice sensitized and challenged to ovalbumin (OVA) three times a
      week for 5 consecutive weeks were administered ONO-1301 or vehicle twice a day
      from the fourth week of OVA challenges. Twenty-four hours after the final OVA
      challenge, airway hyperresponsiveness (AHR) was assessed, and bronchoalveolar
      lavage was performed. Lung specimens were excised for staining to detect goblet
      cell metaplasia, airway smooth muscle, and submucosal fibrosis. Mice administered
      ONO-1301 showed limited increases in AHR compared with mice administered the
      vehicle. The histological findings of airway remodeling were improved in ONO-1301
      treated mice compared with vehicle-treated mice. Presumably, these therapeutic
      effects of ONO-1301 are attributable to the up-regulation of production of
      hepatocyte growth factor (HGF) in lung tissue, because the neutralization of HGF
      by antibodies prevented the effects of ONO-1301 on AHR and airway remodeling.
      Mice administered ONO-1301 showed similar levels of AHR and airway remodeling as
      mice administered montelukast, a cysteinyl-leukotriene-1 receptor antagonist, and
      lower levels were observed in mice administered dexamethasone. These data suggest
      that ONO-1301 exerts the effect of reversing airway remodeling, at least in part
      through an elevation of HGF in the lungs, and may be effective as an anti
      remodeling drug in the treatment of asthma.

PMID- 22403805
TI  - Inositol-trisphosphate reduces alveolar apoptosis and pulmonary edema in neonatal
      lung injury.
AB  - D-myo-inositol-1,2,6-trisphosphate (IP3) is an isomer of the naturally occurring
      second messenger D-myo-inositol-1,4,5-trisphosphate, and exerts anti-inflammatory
      and antiedematous effects in the lung. Myo-inositol (Inos) is a component of IP3,
      and is thought to play an important role in the prevention of neonatal pulmonary
      diseases such as bronchopulmonary dysplasia and neonatal acute lung injury
      (nALI). Inflammatory lung diseases are characterized by augmented acid
      sphingomyelinase (aSMase) activity leading to ceramide production, a pathway that
      promotes increased vascular permeability, apoptosis, and surfactant alterations.
      A novel, clinically relevant triple-hit model of nALI was developed, consisting
      of repeated airway lavage, injurious ventilation, and lipopolysaccharide
      instillation into the airways, every 24 hours. Thirty-five piglets were
      randomized to one of four treatment protocols: control (no intervention),
      surfactant alone, surfactant + Inos, and surfactant + IP3. After 72 hours of
      mechanical ventilation, lungs were excised from the thorax for subsequent
      analyses. Clinically, oxygenation and ventilation improved, and extravascular
      lung water decreased significantly with the S + IP3 intervention. In pulmonary
      tissue, we observed decreased aSMase activity and ceramide concentrations,
      decreased caspase-8 concentrations, reduced alveolar epithelial apoptosis, the
      reduced expression of interleukin-6, transforming growth factor-beta1, and
      amphiregulin (an epithelial growth factor), reduced migration of blood-borne
      cells and particularly of CD14(+)/18(+) cells (macrophages) into the airspaces,
      and lower surfactant surface tensions in S + IP3-treated but not in S + Inos
      treated piglets. We conclude that the admixture of IP3 to surfactant, but not of
      Inos, improves gas exchange and edema in our nALI model by the suppression of the
      governing enzyme aSMase, and that this treatment deserves clinical evaluation.

PMID- 22403806
TI  - Re: "The Association between living through a prolonged economic depression and
      the male:female birth ratio--a longitudinal study from Cuba, 1960-2008" and
      "Invited commentary: Natural versus unnatural sex ratios--a quandary of modern
      times".

PMID- 22403807
TI  - Uptake of pneumococcal polysaccharide vaccination among working-age adults with
      underlying medical conditions, United States, 2009.
AB  - Since 1997, the Advisory Committee on Immunization Practices has recommended the
      23-valent pneumococcal polysaccharide vaccine (PPSV23) for nonelderly adults with
      certain medical conditions. In 2008, the Committee added asthma and cigarette
      smoking to the list of indications for PPSV23 vaccination. Using data from the
      2009 National Health Interview Survey, the authors assessed PPSV23 uptake in
      people with established and new indications. To identify factors independently
      associated with receiving PPSV23, they used multivariable logistic regression and
      predictive marginal analyses. In 2009, a total of 35.2 million adults 18-64 years
      of age (18.6%) had established PPSV23 indications; adding asthma and smoking to
      the list of indications increased the high-risk population to 71.6 million people
      (37.9%). Overall, 26.1% of people with established indications for PPSV23 and
      17.4% of people with any indication (those previously established, as well as
      asthma and smoking) had received the vaccine; overall coverage among persons 50
      64 years of age was significantly higher than that among persons 18-49 years of
      age (34.6% vs. 16.7%; P < 0.001) and for all specific indications except cancer.
      For persons who had asthma or who smoked but had no other indications, rates of
      coverage were 12.3% and 8.5%, respectively. In persons who had established
      indications, being older, white, and unemployed and having more physician visits,
      a prior hospitalization, a regular physician, and health insurance were
      independently associated with PPSV23 receipt. PPSV23 uptake varies substantially
      by age and indication but remains low overall, with approximately 59 million
      unvaccinated high-risk working-age adults. Effective strategies to increase
      pneumococcal vaccination coverage among at-risk groups are needed.

PMID- 22403808
TI  - Developmental hemostasis: recommendations for laboratories reporting pediatric
      samples.

PMID- 22403809
TI  - Persian Gulf states outline regional approach to tackle cancer.

PMID- 22403810
TI  - NICE guidance on dasatinib, high-dose imatinib, and  nilotinib for patients with
      CML who are resistant or  intolerant to imatinib.

PMID- 22403811
TI  - NICE guidance on rituximab for first-line treatment of symptomatic stage III-IV
      follicular lymphoma in previously untreated patients.

PMID- 22403812
TI  - The SCAR project: compassion through reality.

PMID- 22403813
TI  - Trial by media.

PMID- 22403814
TI  - Voices from the front: February.

PMID- 22403815
TI  - Retirement: Sticking around.

PMID- 22403818
TI  - Pain in dementia: recognition and treatment.
AB  - The presentation and management of pain in older adults with dementia are highly
      complicated. This article addresses assessment challenges and nonpharmacological
      and pharmacological management strategies related to pain in those with dementia.
      Vigilant monitoring of comfort level and the effective use of multidimensional
      pain management strategies could substantially increase quality of life for older
      adults with dementia.

PMID- 22403816
TI  - Serum proteomic profiling in patients with drug-induced liver injury.
AB  - BACKGROUND: Idiosyncratic drug-induced liver injury (DILI) is a complex disorder
      that is difficult to predict, diagnose and treat. AIM: To describe the global
      serum proteome of patients with DILI and controls. METHODS: A label-free, mass
      spectrometry-based quantitative proteomic approach was used to explore protein
      expression in serum samples from 74 DILI patients (collected within 14 days of
      DILI onset) and 40 controls. A longitudinal analysis was conducted in a subset of
      21 DILI patients with available 6-month follow-up serum samples. RESULTS:
      Comparison of DILI patients based on pattern, severity and causality assessment
      of liver injury revealed many differentially expressed priority 1 proteins among
      groups. Expression of fumarylacetoacetase was correlated with alanine
      aminotransferase (ALT; r = 0.237; P = 0.047), aspartate aminotransferase (AST; r
      = 0.389; P = 0.001) and alkaline phosphatase (r = -0.240; P = 0.043), and this
      was the only protein with significant differential expression when comparing
      patients with hepatocellular vs. cholestatic or mixed injury. In the longitudinal
      analysis, expression of 53 priority 1 proteins changed significantly from onset
      of DILI to 6-month follow-up, and nearly all proteins returned to expression
      levels comparable to control subjects. Ninety-two serum priority 1 proteins with
      significant differential expression were identified when comparing the DILI and
      control groups. Pattern analysis revealed proteins that are components of
      inflammation, immune system activation and several hepatotoxicity-specific
      pathways. Apolipoprotein E expression had the greatest power to differentiate
      DILI patients from controls (89% correct classification; AUROC = 0.97).
      CONCLUSION: This proteomic analysis identified differentially expressed proteins
      that are components of pathways previously implicated in the pathogenesis of
      idiosyncratic drug-induced liver injury.

PMID- 22403819
TI  - Dmd of bacteriophage T4 functions as an antitoxin against Escherichia coli LsoA
      and RnlA toxins.
AB  - Enterohaemorrhagic Escherichia coli O157:H7 harbours a cryptic plasmid, pOSAK1,
      that carries only three ORFs: mobA (involved in plasmid mobilization), ORF1 and
      ORF2. Predicted proteins encoded by these two ORFs were found to share a weak
      homology with RnlA and RnlB, respectively, a toxin-antitoxin system encoded on
      the E. coli K-12 chromosome. Here, we report that lsoA (ORF1) encodes a toxin and
      lsoB (ORF2) an antitoxin. In spite of the homologies, RnlB and LsoB functioned as
      antitoxins against only their cognate toxins and not interchangeably with each
      other. Interestingly, T4 phage Dmd suppressed the toxicities of both RnlA and
      LsoA by direct interaction, the first example of a phage with an antitoxin
      against multiple toxins.

PMID- 22403820
TI  - Light-dependent and asynchronous replication of  cyanobacterial multi-copy
      chromosomes.
AB  - While bacteria such as Escherichia coli and Bacillus subtilis harbour a single
      circular chromosome, some freshwater cyanobacteria have multiple chromosomes p er
      cell. The detailed mechanism(s) of cyanobacterialreplication remains unclear. To
      elucidate the replication origin (ori ), form and synchrony of the multi-copy
      genome in freshwater cyanobacteria Synechococcus elongatus PCC 7942 we
      constructed strain S. 7942TK that can incorporate 5-bromo-2'- deoxyuridine (BrdU)
      into genomic DNA and analysed its de novo DNA synthesis. The uptake of BrdU was
      blocked under dark and resumed after transfer of the culture to light conditions.
      Mapping analysis of nascent DNA fragments using a next-generation sequencer
      indicated that replication starts bidirectionally from a single ori, which
      locates in the upstream region of the dnaN gene. Quantitative analysis of BrdU
      labelled DNA and whole-genome sequence analysis indicated that the peak timing of
      replication precedes that of cell division and that replication is initiated
      asynchronously not only among cell populations but also among the multi-copy
      chromosomes. Our findings suggest that replication initiation is regulated less
      stringently in S. 7942 than in E. coli and B. subtilis.

PMID- 22403821
TI  - The emerging importance of the SPX domain-containing proteins in phosphate
      homeostasis.
AB  - Plant growth and development are strongly influenced by the availability of
      nutrients in the soil solution. Among them, phosphorus (P) is one of the most
      essential and most limiting macro-elements for plants. In the environment, plants
      are often confronted with P starvation as a result of extremely low
      concentrations of soluble inorganic phosphate (Pi) in the soil. To cope with
      these conditions, plants have developed a wide spectrum of mechanisms aimed at
      increasing P use efficiency. At the molecular level, recent studies have shown
      that several proteins carrying the SPX domain are essential for maintaining Pi
      homeostasis in plants. The SPX domain is found in numerous eukaryotic proteins,
      including several proteins from the yeast PHO regulon, involved in maintaining Pi
      homeostasis. In plants, proteins harboring the SPX domain are classified into
      four families based on the presence of additional domains in their structure,
      namely the SPX, SPX-EXS, SPX-MFS and SPX-RING families. In this review, we
      highlight the recent findings regarding the key roles of the proteins containing
      the SPX domain in phosphate signaling, as well as providing further research
      directions in order to improve our knowledge on P nutrition in plants, thus
      enabling the generation of plants with better P use efficiency.

PMID- 22403822
TI  - Exploiting natural variation to uncover candidate genes that control element
      accumulation in Arabidopsis thaliana.
AB  - The plant ionome varies both inter- and intraspecifically despite the highly
      conserved roles for particular elements across the plant kingdom. Element storage
      requires transport across the plasma membrane and commonly deposition within the
      central vacuole. Therefore, tonoplast transport characteristics can be highly
      influential in controlling the plant ionome. As a result, individual cell types
      of the same plant, each with unique transcriptomes and vacuolar proteomes, can
      display very different elemental profiles. Here we address the use of natural
      variation in Arabidopsis thaliana for identifying genes involved in elemental
      accumulation. We present a conceptual framework, exploiting publicly available
      leaf ionomic and transcriptomic data across 31 Arabidopsis accessions, that
      promises to accelerate conventional forward genetics approaches for candidate
      gene discovery. Utilizing this framework, we identify numerous genes with
      documented roles in accumulation of calcium, magnesium and zinc and implicate
      additional candidate genes. Where appropriate, we discuss their role in cell
      specific elemental accumulation. Currently, this framework could represent an
      alternate approach for identifying genes suitable for element biofortification of
      plants. Integration of additional cell-specific and whole-plant 'omics' datasets
      across Arabidopsis accessions under diverse environmental conditions should
      enable this concept to be developed into a scalable and robust tool for linking
      genotype and phenotype.

PMID- 22403823
TI  - Lateral root initiation: one step at a time.
AB  - Plant growth relies heavily on a root system that is hidden belowground, which
      develops post-embryonically through the formation of lateral roots. The de novo
      formation of lateral root organs requires tightly coordinated asymmetric cell
      division of a limited number of pericycle cells located at the xylem pole. This
      typically involves the formation of founder cells, followed by a number of
      cellular changes until the cells divide and give rise to two unequally sized
      daughter cells. Over the past few years, our knowledge of the regulatory
      mechanisms behind lateral root initiation has increased dramatically. Here, I
      will summarize these recent advances, focusing on the prominent role of auxin and
      cell cycle activity, and elaborating on the three key steps of pericycle cell
      priming, founder cell establishment and asymmetric cell division. Taken together,
      recent findings suggest a tentative model in which successive auxin response
      modules are crucial for lateral root initiation, and additional factors provide
      more layers of control.

PMID- 22403824
TI  - Oomycete and fungal effector entry, a microbial Trojan horse.
AB  - Oomycete and fungal symbionts have significant impacts on most commercially
      important crop and forest species, and on natural ecosystems, both negatively as
      pathogens and positively as mutualists. Symbiosis may be facilitated through the
      secretion of effector proteins, some of which modulate a variety of host defense
      mechanisms. A subset of these secreted proteins are able to translocate into host
      cells. In the oomycete pathogens, two conserved N-terminal motifs, RXLR and dEER,
      mediate translocation of effector proteins into host cells independent of any
      pathogen-encoded machinery. An expanded 'RXLR-like' motif [R/K/H]X[L/M/I/F/Y/W]X
      has been used to identify functional translocation motifs in host-cell-entering
      fungal effector proteins from pathogens and a mutualist. The RXLR-like
      translocation motifs were required for the fungal effectors to enter host cells
      in the absence of any pathogen-encoded machinery. Oomycete and fungal effectors
      with RXLR and RXLR-like motifs can bind phospholipids, specifically
      phosphatidylinositol-3-phosphate (PtdIns-3-P). Effector-PtdIns-3-P binding
      appears to mediate cell entry via lipid raft-mediated endocytosis, and could be
      blocked by sequestering cell surface PtdIns-3-P or by utilizing inositides that
      competitively inhibit effector binding to PtdIns-3-P. These findings suggest that
      effector blocking technologies could be developed and utilized in a variety of
      important crop species against a broad spectrum of plant pathogens.

PMID- 22403825
TI  - Allometric covariation: a hallmark behavior of plants and leaves.
AB  - Size is one of the most important axes of variation among plants. As such, plant
      biologists have long searched for unifying principles that can explain how matter
      and energy flux and organ partitioning scale with plant size. Several recent
      models have proposed a universal biophysical basis for numerous scaling phenomena
      in plants based on vascular network geometry. Here, we review statistical
      analyses of several large-scale plant datasets that demonstrate that a true
      hallmark of plant form variability is systematic covariation among traits. This
      covariation is constrained by allometries that combine and trade off with one
      another, rather than any single universal allometric scaling exponent for a trait
      or suite of traits. Further, we show that covariation can be successfully modeled
      using network approaches that allow for species-specific designs in plants and
      geometric approaches that constrain relationships among economic traits in
      leaves. Finally, we report large-scale efforts utilizing semi-automated software
      tools that quantify physical networks and can inform our attempts to link
      vascular network structure to plant form and function. Collectively, this work
      highlights how the linking of morphology, biomass partitioning and the structure
      of physical distribution networks can improve our empirical and theoretical
      understanding of important drivers of plant functional diversity.

PMID- 22403826
TI  - Unilateral nevoid telangiectasias with anemic halos: why aren't they twin spots?

PMID- 22403827
TI  - In vitro toxicity and genotoxicity assessment of disinfection by-products,
      organic N-chloramines.
AB  - Disinfection by-products (DBPs) are of concern to both water industries and
      health authorities. Although several classes of DBPs have been studied, and there
      are regulated safe levels in disinfected water for some, a large portion of DBPs
      are not characterized, and need further investigation. Organic N-chloramines are
      a group of DBPs, which can be formed during common disinfection processes such as
      chlorination and chloramination, but little is known in terms of their
      toxicological significance if consumed in drinking water. Only a few in vitro
      studies using bacterial assays have reported some genotoxic potential of organic
      N-chloramines, largely in the context of inflammatory processes in the body
      rather than exposure through drinking water. In this study, we investigated 16
      organic N-chloramines produced by chlorination of model amino acids and amines.
      It was found that within the drinking water-relevant micromolar concentration
      range, four compounds were both cytotoxic and genotoxic to mammalian cells. A
      small reduction of cellular GSH was also observed in the treatment with these
      four compounds, but not of a magnitude to account for the cytotoxicity and
      genotoxicity. The results presented in this study demonstrate that some organic N
      chloramines, at low concentrations that might be present in disinfected water,
      can be harmful to mammalian cells.

PMID- 22403828
TI  - A strategy for depositing different types of cells in three dimensions to mimic
      tubular structures in tissues.
AB  - The fabrication of tubular structures, with multiple cell types forming different
      layers of the tube walls, is described using a stress-induced rolling membrane
      (SIRM). Cell orientation inside the tubes can also be controlled by topographical
      contact guidance. These layered tubes precisely mimic blood vessels and many
      other tubular structures, suggesting that they may be of great use in tissue
      engineering.

PMID- 22403829
TI  - Charge reorganization energy and small polaron binding energy of rubrene thin
      films by ultraviolet photoelectron spectroscopy.
AB  - The hole-phonon coupling of a rubrene monolayer on graphite is measured by means
      of angle resolved ultraviolet photoelectron spectroscopy. Thus, the charge
      reorganization energy lambda and the small polaron binding energy is determined,
      which allows insight into the nature of charge transport in condensed rubrene.

PMID- 22403830
TI  - Efficiency enhancement of organic solar cells by fabricating periodic surface
      textures using direct laser interference patterning.
AB  - Direct laser interference patterning (DLIP) is used to fabricate large area, two
      dimensional periodic surface patterns on polyethylene terephthalate (PET)
      substrates to enhance the performance of ZnPc:C60 solar cells by light
      concentration in the absorber layer. Comparing the power conversion efficiencies
      to the reference cell on flat PET, a relative increase of 21% is observed for the
      hexagonal pattern with 0.7 MUm period, depicted in the figure.

PMID- 22403831
TI  - High-performance n-type organic semiconductors: incorporating specific electron
      withdrawing motifs to achieve tight molecular stacking and optimized energy
      levels.
AB  - Novel pi-conjugated cyanostilbene-based semiconductors (Hex-3,5-TFPTA and Hex-4
      TFPTA) with tight molecular stacking and optimized energy levels are synthesized.
      Hex-4-TFPTA exhibits high-performance n-type organic field-effect transistor
      (OFET) properties with electron mobilities as high as 2.14 cm2 V-1s-1 and on-off
      current ratios

PMID- 22403832
TI  - WO3-x@Au@MnO2 core-shell nanowires on carbon fabric for high-performance flexible
      supercapacitors.
AB  - WO3-x@Au@MnO2 core-shell nanowires (NWs) are synthesized on a flexible carbon
      fabric and show outstanding electrochemical performance in supercapacitors such
      as high specific capacitance, good cyclic stability, high energy density, and
      high power density. These results suggest that the WO3-x@Au@MnO2 NWs have
      promising potential for use in high-performance flexible supercapacitors.

PMID- 22403833
TI  - An interview with Robert J. Lefkowitz.

PMID- 22403834
TI  - Adaptation in chemoreceptor cells. II. The effects of cross-adapting backgrounds
      depend on spectral tuning.
AB  - 1. The cross-adapting effects of chemical backgrounds on the response of primary
      chemoreceptor cells to superimposed stimuli were studied using NH(4) receptor
      cells, of known spectral tuning from the lobster (Homarus americanus). 2.
      Spectrum experiments: The spectral tuning of NH(4) receptor cells was
      investigated using NH(4)C1 and 7 other compounds selected as the most stimulatory
      non-best compounds for NH(4) cells from a longer list of compounds tested in
      previous studies. Based on their responses to the compounds tested, 3 spectral
      subpopulations of NH(4) Bet cells which responded second-best to Betaine (Bet;
      and 'pure' NH(4) cells, which responded to NH(4)C1 only (Fig.1). 3. Cross
      adaptation experiments: Overall, cross-adaptation with Glu and Bet backgrounds
      caused suppression of response of NH(4) receptor cells to various concentrations
      of NH(4)C1. However, the different subpopulations of NH(4) cells were affected
      differently: (a) The stimulus-response functions of NH(4)-Glu cells were
      significantly suppressed by both a 3 micrometre (G3) and 300 micrometre (G300)
      Glu backgrounds. (b) The stimulus-response functions of NH(4)-Bet cells was not
      affected by a 3 micrometre (B3), but significantly suppressed by a 300 micrometre
      (B300) Bet background. (c) The stimulus-response functions of pure NH(4) cells
      were not affected by any of the Glu or Bet back grounds (Figs. 3, 4). 4. The
      stimulus-response functions of 5 cells from all different subpopulations were
      enhanced by cross-adaptation with the G300 and B300 back-grounds (Fig 4, Table
      1). 5. Whereas self-adaptation caused parallel shifts in stimulus-response
      functions (Borroni and Atema 1988), cross-adaptation caused a decrease in slope
      of stimulus-response functions. Implications of the results from cross- and self
      adaptation experiments on NH(4) receptor cells, for a receptor cell model are
      discussed.

PMID- 22403835
TI  - [The light induced transformations of chlorophyll studied with differential
      spectrophotometry].

PMID- 22403836
TI  - The historical collection, the library of the Institute for the History of
      Medicine, John Hopkins University.

PMID- 22403837
TI  - Long-term care: facility quality and safety.

PMID- 22403838
TI  - Long-term care: end-of-life issues.

PMID- 22403839
TI  - Long-term care: home- and community-based services.

PMID- 22403840
TI  - Access to health insurance: State Children's Health Insurance Program.

PMID- 22403841
TI  - Access to health insurance.

PMID- 22403842
TI  - Pharmaceuticals and medical devices: medical devices.

PMID- 22403843
TI  - Pharmaceuticals and medical devices: cost savings.

PMID- 22403844
TI  - Pharmaceuticals and medical devices: Medicare Part D.

PMID- 22403845
TI  - Pharmaceuticals and medical devices: FDA oversight.

PMID- 22403846
TI  - Healthcare reform: administrative rulemaking.

PMID- 22403848
TI  - Healthcare reform: insurance market reform.

PMID- 22403849
TI  - Healthcare reform: payment reform.

PMID- 22403850
TI  - Healthcare reform: enforcement and compliance.

PMID- 22403851
TI  - Healthcare reform: state specific responses.

PMID- 22403852
TI  - We can talk. Can we communicate?

PMID- 22403853
TI  - Deafness as metaphor, and partnerships in practice in 2012.

PMID- 22403854
TI  - The sounds of silence: exploring lessons about silence, listening, and presence.
AB  - Unless we--in our professional and nonprofessional roles--learn the importance
      and practice of deliberate silence, engaged listening, and restrained response,
      we will miss the opportunity to provide our presence and comfort to those about
      whom we care. And unless we--as health care professionals--learn these lessons,
      we will miss the opportunity to do all of that and provide a more accurate,
      complete diagnosis and informed plan of treatment. Done well, these practices
      have application to all our relationships with patients, colleagues, family, and
      friends.

PMID- 22403855
TI  - Sensitive care for the deaf: a cultural challenge.
AB  - Of the more than 36 million American adults who have some degree of hearing loss
      (Centers for Disease Control and Prevention [CDC], 2008), 500,000 are
      acculturated into the culturally Deaf community who share behavioral norms,
      values, customs, educational institutions, and organizations. This article
      discusses the Deaf community, their culturally based health care needs, and
      health care providers' (HCPs) lack of understanding and recognition of Deafness
      as a distinct culture, which individually or cumulatively result in barriers to
      culturally sensitive care that can lead to disparities in care. It suggests
      transcultural methods HCPs can use to narrow the cultural divide.

PMID- 22403856
TI  - Pictures of a client's silent distress.
AB  - A trust-based nurse-patient relationship and open communication can help nurses
      alleviate clients' intrapersonal and interpersonal distress. However, the
      client's silence about unspoken needs can present an obstacle to successful
      holistic care. This article describes how pictures, both mental and printed, can
      be used by nurses to open pathways of healing communication and holistic nursing
      care.

PMID- 22403857
TI  - Music's unspoken messages.
AB  - Today, integrative medicine encompasses many healing arts therapies, including
      music. The universal language of music is simple, yet often forgotten, and
      communicates unspoken messages. The healing power of music in the health care
      setting creates a healing environment, distracts from pain, relaxes and de
      stresses, and helps with sleep.

PMID- 22403858
TI  - Works of art as a pedagogical tool: an alternative approach to education.
AB  - Contemporary authors on nursing issues discuss the importance of expanding
      knowledge at all levels of nursing education to empower future nurses to respond
      in caring situations for the benefit of their patients. This article reviews
      several studies in which paintings, complemented by a pedagogical structure,
      allowed students to observe situations relevant to nursing. Results suggest that
      the use of visual art in nursing education can add a new dimension to students'
      experiences.

PMID- 22403859
TI  - Canine communication.
AB  - A Seeing Eye dog handler discusses nonverbal, nonvocal communication between
      human and animal. Each gesture and nonverbal element from dog to master and vice
      versa shows intricate patterns of communication that can relate to patient care.

PMID- 22403860
TI  - The unspoken exchange between two human beings.
AB  - Even though the English language is full of complex words that help us to express
      ourselves and connect with each other through speech, most communication between
      two human beings transpires without the use of words. Human beings begin
      communicating as soon as their energy fields cross; and this exchange can lead to
      even greater insight when it takes place in someone's home.

PMID- 22403861
TI  - Conversation and much more.

PMID- 22403862
TI  - Transient cell function disruption by low dose acute exposure of ionizing
      radiation.
AB  - Incubation of BMG-1 cells with thallium chloride (201Tl) in the range of
      diagnostic dose did not show a smooth uptake curve and appeared to have an
      unsuspected deviation in initial phase. In the present study this unexpected
      phenomenon was explored, using commonly used radionuclides (viz., 201Tl and
      131I). Comparison was made with technetium-99m pertechnetate (99mTcO4(-)) and
      technetium-99m labeled methoxyisobutylisonitrile (99mTc-MIBI) that are known to
      show conventional 2 phase graph representing inflow and outflow segments. Serial
      in vitro, ex-vivo and in vivo gamma scintigraphy as well as NMR spectroscopy
      experiments were conducted to corroborate the results. BMG-1 cells demonstrated a
      four-phase uptake pattern with 201Tl as compared to a conventional biphasic
      pattern with 99mTc-MIBI. Flow cytometry data however did not reveal any 201Tl
      induced cell injury. Further, mice tissue extracts injected with 201Tl also
      showed a transient depression in its uptake. Scintigraphy experiments in rabbits
      administered with diagnostic dose of 201Tl and 131I confirmed the in vitro and ex
      vivo findings. Further, proton NMR spectroscopy showed decrease in the level of
      choline at 3 h and 24 h in 201Tl treated animals as compared to control.
      Phosphoethanolamine peak firstly decreased at 3 h but reached normal level at 24
      h time point. No significant change was observed in the level of betaine. This
      transient reduction in internalization of 201Tl and 131I may represent a hitherto
      unknown acute effect of low dose radiation, i.e., transient depression in Na+-K+
      ATPase pump activity without any apparent evidence of cell damage, representing a
      transient cell membrane dysfunction. The phenomenon may present a mechanistical
      explanation of 'thyroid stunning' at cellular level and suggest that it may be
      more universal in nature than suspected till now.

PMID- 22403863
TI  - Inhibition of platelet aggregation and immunomodulation of NK lymphocytes by
      administration of ascorbic acid.
AB  - Platelets aggregation around migrating tumor cells offers protection against the
      cytotoxic activity of the natural killers cells (NKC). The ascorbic acid in 3 x
      10(-3) M concentration completely inhibited platelet aggregation, decreased
      thromboxane B2 levels, and inhibited the expression of platelet membranic
      receptor GpIIb/IIIa in non stimulated platelets, and increased the NKC
      cytotoxicity in an average rate of 105, 61, and 285% in the NKC/targets cells
      ratios 12.5:1, 25:1 and 50:1 respectively. The results suggest the role of
      ascorbic acid in increasing the susceptibility of tumor cells to NKC; the
      ascorbic acid could be used as part of a multidrug therapy to treat diseases
      which up to now have been treated only through chemotherapy.

PMID- 22403864
TI  - Differential response of tomato and tobacco to Agrobacterium mediated
      transformation with cytokinin independent -1 (CKI-1) gene as influenced by
      cytokinin levels.
AB  - Cytokinin independent-1 (CKI-1) gene was identified through its ability to confer
      cytokinin independent growth in Arabidopsis which has led to this gene being
      advocated as a selectable marker in plant transformation. Keeping this in view,
      CKI-1 gene was assessed as a selectable marker by transformation of tobacco
      (Nicotiana tabacum) and tomato (Lycopersicon esculentum L.). Overexpression of
      CKI-1 gene through Agrobacterium mediated transformation in tobacco and tomato
      conferred cytokinin independent shoot regeneration (in media devoid of
      cytokinin/plant growth regulators) in tobacco, but not in tomato wherein this
      ability (cytokinin independence) was conferred to T1 explants of CKI-1 transgenic
      tomato plant (T0) regenerated on cytokinin medium. Analysis of cytokinin levels
      revealed that cytokinin independent growth upon transformation with CKI-1 gene in
      tobacco (T0) and tomato (T1) was achieved through maintaining/regulating higher
      endogenous cytokinin levels and CKI-1 gene expression. Levels of CKI-1
      transcripts assayed through quantitative RT-PCR suggested that there seemed to be
      a threshold level of endogenous cytokinin level, regulated due to external or
      internal supply via CKI-1 gene upto which CKI-1 gene expression correlated with
      endogenous cytokinin content and beyond that, either the gene expression was not
      induced or it remains same. With the incorporation of CKI-1 gene, it appeared
      that this threshold level of endogenous cytokinin might be reduced in crops like
      tomato to support shoot regeneration at lower concentration of cytokinin, but
      could not be made independent of external supply of cytokinin as in tobacco
      suggesting that use of CKI-1 gene as an effective alternate selection marker
      could not be universally applicable across the species. The results of the
      present study revealed that CKI-1 gene in addition to enhancing cytokinin levels,
      was also involved in contributing to the sensitivity to cytokinin and thus served
      as a positive regulator of cytokinin signal transduction.

PMID- 22403865
TI  - Construction and functional characterization of double and triple mutants of
      parallel beta-bulge of ubiquitin.
AB  - Ubiquitin, a small eukaryotic protein serving as a post-translational
      modification on many important proteins, plays central role in cellular
      homeostasis and cell cycle regulation. Ubiquitin features two beta-bulges, the
      second beta-bulge, located at the C-terminal region of the protein along with
      type II turn, holds 3 residues Glu64(1), Ser65(2) and Gln2(X). Percent frequency
      of occurrence of such a sequence in parallel beta-bulge is very low. However, the
      sequence and structure have been conserved in ubiquitin through out the
      evolution. Present study involves replacement of residues in unusual beta-bulge
      of ubiquitin by introducing mutations in combination through site directed
      mutagenesis, generating double and triple mutants and their functional
      characterization. Mutant ubiquitins cloned in yeast expression vector YEp96
      tested for growth profile, viability assay and heat stress complementation study
      have revealed significant decrease in growth rate, loss of viability and non
      complementation of heat sensitive phenotype with UbE64G-S65D and UbQ2N-E64G-S65D
      mutations. However, UbQ2N-S65D did not show any negative effects in the above
      assays. Present results show that, replacement of residues in beta-bulge of
      ubiquitin exerts severe effects on growth and viability in Saccharomyces
      cerevisiae due to functional failure of the mutant ubiquitins UbE64G-S65D and
      UbQ2N-E64G-S65D.

PMID- 22403866
TI  - In situ Carica papaya stem matrix and Fusarium oxysporum (NCBT-156) mediated
      bioremediation of chromium.
AB  - Removal of heavy metal chromium was carried out using the fungus Fusarium
      oxysporum NCBT-156 strain isolated from soil of leather tanning effluent in in
      situ condition using potassium dichromate solution with 10 per cent Czapek-dox
      liquid medium. Biosorbent matrix was developed using Carica papaya plant dry stem
      to colonize the fungal strain to facilitate bioabsorption process. Bioabsorption
      of chromium was by metabolically mediated intracellular accumulation process.
      Maximum efficiency of chromium removal by biosorption upto 90 per cent was
      achieved at the end of 5th day of incubation (120 h of contact time) for 100 and
      200 ppm concentration, upto 80 per cent for 300 and 400 ppm, and upto 65 per cent
      for 500 ppm to 1000 ppm concentrations with pH ranging from 5.8, 5.6, 5.5, 5.4
      and 5.2, respectively for 100, 200, 300, 400, 500-1000 ppm concentration. SDS
      PAGE protein profile showed significant difference in 34 kDa protein band after
      chromium absorption by the fungus. FTIR spectroscopic analysis revealed that the
      main functional groups involved in the uptake of chromium by F. oxysporium strain
      were carbonyl, carboxyl, amino and hydroxyl groups.

PMID- 22403867
TI  - Anti-inflammatory, analgesic and antipyretic activities of Linum usitatissimum L.
      (flaxseed/linseed) fixed oil.
AB  - The fixed oil of L. usitatissimum (flaxseed/linseed) inhibited PGE2-, leukotriene
      , histamine- and bradykinin-induced inflammation. The oil also inhibited
      arachidonic acid-induced inflammation, suggesting its capacity to inhibit both
      cyclooxygenase and lipoxygenase pathways of arachidonate metabolism. In tail
      immersion model, the oil raised the pain threshold to a lesser extent than
      morphine but showed excellent peripherally acting, analgesic activity comparable
      to aspirin, against acetic acid-induced writhing in mouse. In typhoid paratyphoid
      A/B vaccine-induced pyrexia, the oil showed antipyretic activity comparable to
      aspirin. The oil contains 57.38% alpha-linolenic acid. Dual inhibition of
      arachidonic acid metabolism, antihistaminic and antibradykinin activities of the
      oil could account for the biological activity and the active principle could be
      alpha-linolenic acid an omega-3 (18:3, n-3) fatty acid.

PMID- 22403868
TI  - In vitro and in vivo hepatoprotective activity of Cissampelos pareira against
      carbon-tetrachloride induced hepatic damage.
AB  - Administration of hydroalcoholic extract of Cissampelos pareira roots (CPRE) and
      standard drug silymarin in rats showed significant hepatoprotective action
      against CCl4 induced hepatotoxicity. Elevated serum marker enzymes of AST, ALT,
      ALP and serum bilirubin were significantly reduced to near normal level in CPRE
      treated rats. Lipid peroxidation level was decreased significantly in CPRE 100,
      200, 400 mg/kg doses treatment groups. In case of antioxidant enzymes SOD,
      catalase levels were increased significantly after CPRE 200, 400 mg/kg doses,
      similarly it increased the enzyme levels of GST, GPx, and GSH. CPRE 200, 400
      mg/kg decreased cholesterol level, and increased triglyceride level. In vitro
      hepatoprotective activity of the extract was evaluated at 20, 40, 60, 80 and 100
      microg/ml concentration against CCl4 (1%) induced toxicity in freshly isolated
      rat hepatocytes. HepG2 cells showed significant dose dependent increase in
      percentage viability at the doses 20, 40, 60, 80 and 100 microg/ml of CPRE
      compared to CCl4 exposed HepG2 cells. Results of this study strongly demonstrate
      Cissampelos pariera having good hepatoprotective potential.

PMID- 22403869
TI  - Membrane-active metabolites produced by soil actinomycetes using chromatic
      phospholipid/polydiacetylene vesicles.
AB  - Increased resistance of pathogens toward existing antibiotics has compelled the
      research efforts to introduce new antimicrobial substances. Drugs with new and
      less resistant-prone targets to antimicrobial activity have a high priority for
      drug development activities. Cell membrane seems to be a potential target for new
      antibiotic agent development to overcome resistance. In this study, A total
      number of 67 actinomycetes were isolated from the soil samples collected from
      desert, farming and mineral parts of Iran. We used a chromatic sensor as a
      membrane model that was set up for the target of antimicrobial metabolites of
      actinomycetes isolated from the soil. The sensors particles were composed of
      phospholipid and polymerized polydiacetylene (PDA) lipids. These polymers
      exhibited color change following interaction with membrane-active metabolites.
      The color change was due to structural disorder in the lipids following their
      interaction with membrane-active metabolites. The resultant color change was
      recorded by fluorescent microscope and easily recognizable by naked eye as well.
      Sixteen strains were isolated which produced antimicrobial metabolites and were
      effective against test microorganisms (Escherichia coli, Candida albicans and
      Saccharomyces cerevisiae ). A total number of 3 out of 16 strains produced
      membrane-active metabolites. These 3 strains were identified using 16s rRNA as
      Streptomyces sp and submitted to GenBank (accession no. JN180853; JN180854;
      JN180855).

PMID- 22403870
TI  - DNA extraction from crayfish exoskeleton.
AB  - Crayfish exoskeleton (CE) samples are generally less invasive and easy to be
      collected. However, it is difficult to extract DNA from them. This study was
      intended to investigate CE as a DNA source and design an easy and efficient DNA
      extraction protocol for polymerase chain reactions. Specific primer pair (PPO-F,
      PPO-R) was used to amplify extracted DNA from CE, and compared to crayfish tail
      muscle DNA sample. Moreover, seven microsatellites markers were used to amplify
      the CE DNA samples set. Since the extracted DNA from CE is suitable for gene
      amplification, the results present usefulness of CE as an easy and convenient DNA
      source for PCR-based population genetic research.

PMID- 22403871
TI  - Protocol for in vitro somatic embryogenesis and regeneration of rice (Oryza
      sativa L.).
AB  - Development of highly efficient and reproducible plant regeneration system has
      tremendous potential to provide improved technology to assist in genetic
      transformation of indica rice cultivars for their further exploitation in
      selection. For the development of a highly reproducible regeneration system
      through somatic embryogenesis, mature embryos of highly popular rice cultivars
      i.e., Govind (for rainfed areas), Pusa Basmati-1 (aromatic basmati) and Jaya (for
      irrigated areas) were used. Optimum callus formation (%) to MS medium
      supplemented with 2, 4-D was obtained at 12.0 microM in Govind, 14.0 microM in
      Jaya and 15.0 microM in Pusa Basmati-1. All the cultivars showed good
      proliferation on MS medium without hormone. In Govind, highest embryogenic
      response was observed in MS medium supplemented with 2, 4-D (0.4 microM) +
      kinetin (0.4 microM), while in Pusa Basmati-1 with 2, 4-D (0.4 microM) + kinetin
      (2.0 microM) and in Jaya on hormone-free MS medium. Excellent embryo regeneration
      in Govind was observed on MS medium supplemented with low concentrations (1.1
      microM) of BAP or hormone-free MS medium, while in Pusa Basmati-1 and Jaya
      embryogenesis was observed on MS medium supplemented with higher concentration of
      BAP (2.2 microM). Similarly, maximum plantlets with proliferated roots were
      observed in Govind on hormone-free MS medium, while in Pusa Basmati-1 and Jaya on
      MS medium supplemented with high concentration of NAA (4.0 microM). Developed
      plantlets were further successfully acclimatized and grown under pot culture up
      to maturity. Further the yield potential of in vitro developed plants was
      accessed at par to the direct seeded one under pot culture. Present, protocol
      standardizes somatic embryogenesis and efficient regeneration of agronomically
      important, high yielding and diverse indica rice cultivars which can be utilized
      as an efficient tool for molecular studies and genetic transformation in future.

PMID- 22403872
TI  - [Impact of adipose-derived stem cells combined with vascular bundle implantation
      on vascularized tissue engineering scaffolds in vivo].
AB  - OBJECTIVE: To discuss the impact of adipose-derived stem cells (ADSCs) combined
      with vascular bundle implantation on vascularized tissue engineering scaffolds in
      vivo so as to provide a theoretical basis for the repair of avascular necrosis of
      the femoral head. METHODS: ADSCs were isolated from 4-month-old Sprague Dawley
      (SD) rats and cultured, then were induced to osteogenesis and identified. ADSCs
      at the 3rd passage were seeded on the nano-hydroxyapatite/polyamide-66 (nHA/PA66)
      to prepare the composite scaffolds. The compound condition of cells and scaffold
      materials were observed under scanning electronic microscope (SEM). Twenty-four 4
      month-old SD rats (weighing 350-400 g) were randomly divided into 3 groups (n=8).
      In group A and group B, the inferior epigastric artery and vein of rats were
      implanted into composite scaffold cultured for 10 days or simple nHA/PA66
      scaffold, respectively. In group C, two composite scaffolds cultured for 10 days
      were embedded into quadriceps femoris muscle of both thighs, respectively. After
      2 and 4 weeks of operation, angiogenesis was observed by HE staining and CD34
      immunohistochemical staining. RESULTS: Cells isolated from adipose were
      identified as ADSCs. SEM showed that the number of cells increased after being
      cultured for 10 days, cell morphology stretched fully with a shape of long
      spindle. HE staining and immunohistochemical staining showed that a large number
      of angiogenesis was observed around the implanted artery and vein in group A,
      which was superior to groups B and C in the number of blood vessels and the
      maturity of blood vessel wall. After 2 and 4 weeks of operation, the blood vessel
      density and blood vessel diameter were significantly higher in group A than in
      group B and group C, and in group B than in group C (P < 0.05). CONCLUSION:
      Combined application of ADSCs and vascular bundle implantation can promote the
      degree of vascularization, which could make the scaffold vascularization
      reliable.

PMID- 22403873
TI  - [Experimental study on dermal papillary cells improving vascularization of tissue
      engineered skin substitutes].
AB  - OBJECTIVE: To investigate the impact of dermal papillary cells on vascularization
      of tissue engineered skin substitutes consisting of epidermal stem cells and
      allogeneic acellular dermal matrix. METHODS: Human foreskins from routine
      circumcisions were collected to separate epidermal cells by using dispase with
      trypsinogen. Collagen type IV was used to isolate epidermal stem cells from the
      2nd and 3rd passage keratinocytes. Dermal papilla was isolated by the digestion
      method of collagenase I from fetus scalp and cultured in routine fibroblast
      medium. Tissue engineered skin substitutes were reconstructed by seeding
      epidermal stem cells on the papillary side of allogeneic acellular dermis with
      (the experimental group) or without (the control group) seeding dermal papillary
      cells on the reticular side. The two kinds of composite skin substitutes were
      employed to cover skin defects (1 cm x 1 cm in size) on the back of the BALB/C-nu
      nude mice (n=30). The grafting survival rate was recorded 2 weeks after grafting.
      HE staining and immunohistochemistry method were employed to determine the
      expression of CD31 and calculate the microvessel density at 2 and 4 weeks after
      grafting. RESULTS: Those adhesion cells by collagen type IV coexpressed Keratin
      19 and beta1 integrin, indicating that the cells were epidermal stem cells. The
      cultivated dermal papillary cells were identified by expressing high levels of a
      smooth muscle actin. The grafting survival rate was significantly higher in
      experimental group (28/30, 93.3%), than that in control group (24/30, 80.0%). HE
      staining showed that the epithelial layer in experimental group was 12-layered
      with large epithelial cells in the grafted composite skin, and that the
      epithelial layer in control group was 4-6-layered with small epithelial cells. At
      2 and 4 weeks after grafting, the microvessel density was (38.56 +/- 2.49)/mm2
      and (49.12 +/- 2.39)/mm2 in experimental group and was (25.16 +/- 3.73)/mm2 and
      (36.26 +/- 3.24)/mm2 in control group respectively, showing significant
      differences between 2 groups (P < 0.01). CONCLUSION: Addition of dermal papillary
      cells to the tissue engineered skin substitutes can enhance vascularization,
      which promotes epidermis formation and improves the grafting survival rate.

PMID- 22403874
TI  - [Comparative studies on different cryopreservation protocols of human amniotic
      fluid-derived mesenchymal stem cells].
AB  - OBJECTIVE: To isolate and culture human amniotic fluid-derived mesenchymal stem
      cells (HAFMSCs), to investigate a better cryopreservation protocol of HAFMSCs and
      to observe the bio-characteristics and the multi-potential of HAFMSCs after
      cryopreservation for the further fundamental researches and clinical
      applications. METHODS: HAFMSCs were isolated from the amniotic fluid of pregnant
      women during the second trimester by the improved two-step method. HAFMSCs were
      cryopreserved with different cryopreservation protocols (containing different
      contents of FBS and DMSO at cryoprotectant) in liquid nitrogen for 12 weeks. The
      bio-characteristics of the HAFMSCs after cryopreservation were analyzed. The
      growth characteristics were observed by MTT method and the growth curves were
      drawn. The surface antigens of HAFMSCs were detected using flow cytometry,
      including CD29, CD34, CD44, CD45, CD73, and CD90. The adipogenic and osteogenic
      differentiation abilities of HAFMSCs were observed. The mRNA levels of Oct-4 and
      Nanog of the HAFMSCs were compared between before and after cryopreservation.
      RESULTS: At 12 weeks after cryopreservation, different protocols had different
      effects on the cell viability; the better formula of cryoprotectant was 50% DMEM,
      40% FBS, and 10% DMSO. After cryopreservation, the cells proliferated rapidly and
      the growth curves showed "S" shape, which was the same as the cells before
      cryopreservation. Phenotype showed that HAFMSCs were positive for the surface
      markers CD29, CD44, CD73, and CD90, and negative for CD34 and CD45. After 21 days
      of adipogenic differentiation, the lipid droplets were observed by oil red O
      staining. After 21 days of osteogenic differentiation, the calcium mineralization
      were verified by von Kossa staining. There was no significant difference (P >
      0.05) in the mRNA levels of Oct-4 and Nanog between before and after
      cryopreservation. CONCLUSION: HAFMSCs have rapid proliferation and multi
      potential in vitro. The cells have high viabilities and no changes of the bio
      characteristics and differentiation potentialities after cryopreservation for 12
      weeks. Cryoprotectant containing 50% DMEM, 40% FBS, and 10% DMSO is a better
      cryopreservation protocol.

PMID- 22403875
TI  - [Expression of connexin 40 and hyperpolarization-activated cyclic nucleotide
      gated cation channel 4 in rat bone marrow mesenchymal stem cells cocultured with
      sinoatrial node tissues in vitro].
AB  - OBJECTIVE: To investigate the expression of connexin 40 (Cx40) and
      hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4) in
      rat bone marrow mesenchymal stem cells (BMSCs) cocultured with the sinoatrial
      node (SAN) tissues in vitro, so as to evaluate the possibility of BMSCs
      differentiation into SAN cells. METHODS: BMSCs were isolated from Sprague Dawley
      rats (aged 4-6 weeks, male or female) by the adhesive method and cultured; BMSCs
      at the 3rd passage were marked with carboxyfluorescein succinimidyl ester, and
      then were incubated on 6-well culture plate; cell climing slices were prepared at
      the same time. SAN tissue was taken and cut into 0.3 cm x 0.3 cm mass, and then
      placed into 4 degrees C PBS solution. The SAN tissue mass was cocultured with
      marked BMSCs at the 3rd passage for 3 weeks as the experimental group, and BMSCs
      at 3rd passage were cultured alone for 1 week as the control group. At 1, 2, and
      3 weeks after coculture, the mean integrated absorbance (MIA) values of Cx40 and
      HCN4 were measured by Image pro plus 5.0 through the method of
      immunohistochemistry, and the mRNA expressions of Cx40 and HCN4 were identified
      by real-time fluorescent quantitative PCR. RESULTS: The MIA values of Cx40 and
      HCN4 in the experimental group were higher than that in the control group,
      showing significant differences (P < 0.01). In the experimental group, the
      expressions of Cx40 and HCN4 increased gradually with time. The longer the
      culture time was, the higher the expressions of Cx40 and HCN4 were, showing
      significant differences (P < 0.05). The mRNA expressions of Cx40 and HCN4 in the
      experimental group were significantly higher than those in the control group (P <
      0.01); in the experimental group, the mRNA expressions of Cx40 and HCN4 increased
      gradually with time, showing significant differences between different time
      points (P < 0.05). CONCLUSION: The expressions of Cx40 and HCN4 increase
      obviously after coculturing BMSCs with SAN tissue, indicating that BMSCs could
      differentiate into SAN cells by coculturing with SAN tissue in vitro.

PMID- 22403876
TI  - [Bio-characteristics of c-kit+ human amniotic fluid-derived mesenchymal stem
      cells and their differentiation into cardiomyocytes in vitro].
AB  - OBJECTIVE: To investigate the bio-characteristics of c-kit+ human amniotic fluid
      derived mesenchymal stem cells (HAFMSCs) and its capacity to differentiate into
      cardiomyocytes in vitro. METHODS: Fifty samples of human amniotic fluid were
      obtained from amniocenteses or voluntary termination of pregnancy and were
      expanded in vitro. c-kit+ HAFMSCs were sorted by flow cytometry and were
      recultured in the same media. c-kit+ HAFMSCs were amplified and identified, then
      exposed to osteogenic, adipogenic, and myogenic media. The flow cytometry, and
      immunocytochemistry were used for identifying the cell phenotype, von Kossa
      staining for osteogenic differentiation, oil red O staining for adipogenic
      differentiation, and real-time fluorescent quantitative PCR for the expressions
      of NKx2.5, Tbx5, GATA-4, and alpha-MHC genes. RESULTS: After the selection
      procedure, the percentage of c-kit+ HAFMSCs was 3.07% +/- 1.03% of the total
      adherent cells. The cells expressed MSCs markers (CD29, CD44, CD73, CD90, CD105),
      and did not express hematopoietic stem cells markers (CD34, CD45). The cells were
      positive for human leukocyte antigen (HLA)-ABC, and negative for HLA-DR. They
      also expressed Oct-4, which characterized the undifferentiated stem cell state.
      The growth curves of c-kit+ HAMFSCs at passages 5, 10, and 15 were similar. Lipid
      droplet was observed by oil red O staining and calcium deposition by von Kossa
      staining in the cells at 21 days after adipogenic and osteogenic induction. The
      myocardium special gene expressions of Tbx5, Nkx2.5, GATA-4, and alpha-MHC were
      significantly stronger after myogenic induction than those before myogenic
      induction (P < 0.05). CONCLUSION: Selected c-kit+ HAFMSCs by flow cytometry is a
      group of pure MSCs, which has potential to differentiate into cardiomyocytes and
      can be used as seeding cells for myocardium regeneration treatment.

PMID- 22403877
TI  - [Effect of salidroside on rat bone marrow mesenchymal stem cells differentiation
      into cholinergic nerve cells].
AB  - OBJECTIVE: To investigate the effect of salidroside on rat bone marrow
      mesenchymal stem cells (BMSCs) differentiation into the cholinergic nerve cells,
      so as to provide the theory basis of the combination of salidroside and stem
      cells for clinical therapy of nervous system diseases. METHODS: BMSCs were
      isolated from 2 Wistar rats (aged 4-6 weeks,weighing 120 g), which were
      identified by CD34, CD45, CD90, and CD106 with flow cytometry. According to
      inducing method, BMSCs at passage 2 were divided into 3 groups: In groups A and
      B, BMSCs were induced by salidroside (20 microg/mL) and retinoic acid (5
      micromol/mL) respectively for 1, 3, 6, and 9 days, in group C, BMSCs were
      cultured with serum-free DMEM/F12 medium as control. MTT assay was used to detect
      the cellular proliferation activity. The immunofluorescence chemical technology
      was used to detect the expressions of nerve growth factor (NGF) and relevant
      marker molecule of nerve cells, including neuron-specific enolase (NSE),
      microtubule-associated protein 2 (MAP2), beta-Tubulin III, glial fibrillary
      acidic protein (GFAP), and the marker of cholinergic neuron, such as
      Acetylcholine (Ach) and NGF. RT-PCR was used to detect mRNA expressions of NSE,
      beta-Tubulin III, GFAP,brain derived neurotrophic factor (BDNF),and gamma
      aminobutyric acid (GABA). ELISA was used to detect the levels of BDNF and NGF,
      and the expression level of NGF protein was analyzed by Western blot. RESULTS:
      The results of the flow cytometry showed that the cultured cells were CD90 and
      CD106 positive, and CD34 and CD45 negative,which indicated that the cells were
      BMSCs. The cellular proliferation activity in groups A and B were significantly
      higher than that in group C at 6 days and 9 days (P < 0.05). RT-PCR results
      showed that the expression level of NSE,BDNF, beta-Tubulin III,GFAPmRNA were
      increased in group A at 6 days; In group B, that expression level of NSE mRNA was
      up-regulated at 6 days, that expression level of BDNF mRNA increased at 1 days
      and reached the peak at 6 days, and that expression level of beta-Tubulin III
      mRNA was up-regulated at 3 days, which was significantly higher than that at the
      other time points, and than that in group C (P < 0.01). But no GABA mRNA
      expression was detected in each group. Immunofluorescence chemical technology
      staining showed that the positive rates of NSE, MAP2, beta-Tubulin III, and GFAP
      were significantly higher in group A than those in group C at 3 days; the
      positive rates of Ach were significantly higher at 3, 6, and 9 days than those at
      1 day in groups A and B, and in groups A and B than in group C (P < 0.01); the
      positive rates of NGF in groups A and B were significantly higher than those in
      group C (P < 0.01). The levels of BDNF and NGF in groups A and B were
      significantly higher than those in group C at 1, 3, 6, and 9 days (P < 0.01), but
      no significant difference of BDNF was found between groups A and B (P > 0.05).
      The expression level of NGF protein in groups A and B were significantly higher
      than that in group C (P < 0.01). The NGF expression reached the peak at 6 days in
      group A and at 3 days in group B. CONCLUSION: Salidroside could induce rat BMSCs
      differentiate into cholinergic nerve cells in vitro.

PMID- 22403878
TI  - [Upregulation of Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 and
      translocation to mitochondria in nucleus pulposus cells induced by nutrition
      deprivation].
AB  - OBJECTIVE: To detect the expression of Bcl-2/adenovirus E1B 19-kDa-interacting
      protein 3 (BNIP3) in cell death induced by nutrition deprivation in nucleus
      pulposus cells so as to further understand the mechanism of death in nucleus
      pulposus cells. METHODS: Two adult Sprague Dawley rats, male or female, weighing
      150-200 g, were involved in this experiment. The cells isolated from rat caudal
      disc were cultured under the condition of L-DMEM culture media, 10%FBS, and 21%O2
      (control group) and under the condition of DMEM-free glucose culture media, no
      serum, and 1% 02 (experimental group). The expressions of BNIP3 gene and protein
      were detected by real-time fluorescent quantitative PCR, immunofluorescence
      staining, and Western blot. The cell apoptosis rate and mitochondrial membrane
      potential were measured by flow cytometry at 24, 48, and 72 hours after culture.
      RESULTS: The expression of BNIP3 decreased in the control group; the expressions
      of BNIP3 showed an increasing tendency with time in the experimental group, and
      BNIP3 combined with mitochondria. Significant differences were observed in the
      expressions of BNIP3 gene and protein between 2 groups at the other time (P <
      0.05) except that no significant difference was observed in the expression of
      BNIP3 gene at 24 hours (P > 0.05). The cell apoptosis rate and mitochondrial
      membrane potential were significantly lower in the experimental group than those
      in the control group (P < 0.05). CONCLUSION: Upregulation of BNIP3 and
      translocation to mitochondria may be involved in nucleus pulposus cell death in
      nutrition deprivation.

PMID- 22403879
TI  - [Construction and identification of recombinant adeno-associated virus shuttle
      vector expressing nerve growth factor beta gene].
AB  - OBJECTIVE: To construct a recombinant adeno-associated virus (AAV) shuttle vector
      expressing nerve growth factor beta (NGF-beta) gene. METHODS: By PCR
      amplification, the structural element of pAAV-multiple cloning site (MCS) and the
      functional element of pGenesil-1.1 were obtained and cloned into T-easy vector,
      respectively; the recombinant T-easy vectors were digested by restriction enzyme,
      then the target fragments were reclaimed and connected by DNA ligase, so the
      recombinant AAV shuttle vector pAAV-U6/CMV-enhanced green fluorescent protein
      (EGFP) containing U6 promoter and CMV promoter was obtained. The vector was
      transfected into 293 cells. The human Miapaca-2 cell line was cultured, and total
      RNA was extracted, then human NGF-beta gene was obtained by RT-PCR. T-easy-NGF
      beta vector was constructed by cloning human NGF-beta gene into T-easy vector and
      identified by RT-PCR, digestion, and DNA sequencing. As NGF-beta gene was cloned
      into pAAV-U6/CMV-EGFP vector, the recombinant AAV shuttle vector expressing NGF
      beta gene was obtained and identified by RT-PCR, digestion, and DNA sequencing.
      RESULTS: The bands of 800 bp and 4 250 bp were detected when pAAV-U6/CMV-EGFP was
      digested. The GFP was detected when pAAV-U6/CMV-EGFP was transfected into 293
      cells. The bands of 736 bp and 3 015 bp were detected when T-easy-NGF-beta was
      digested; DNA sequencing result of T-easy-NGF-beta was fully consistent. The
      bands of 736 bp and 4 250 bp were detected when pAAV-U6/CMV-NGF-beta was
      digested. DNA sequencing result of pAAV-U6/ CMV-NGF-beta showed that sequences
      were completely correct. CONCLUSION: The AAV shuttle vector pAAV-U6/CMV-NGF-beta
      is successfully constructed, providing experimental basis for investigation of
      the repair of spinal cord injury.

PMID- 22403880
TI  - [Construction and identification of Nogo extra cellular peptide residues 1-40
      gene lentiviral vector].
AB  - OBJECTIVE: To construct a lentiviral expression vector carrying Nogo extra
      cellular peptide residues 1-40 (NEP1-40) and to obtain NEP1-40 efficient and
      stable expression in mammalian cells. METHODS: The DNA fragment of NEP1-40 coding
      sequence was amplified by PCR with designed primer from the cDNA library
      including NEP1-40 gene, and then subcloned into pGC-FU vector with in-fusion
      technique to generate the lentiviral expression vector, pGC-FU-NEP1-40. The
      positive clones were screened by PCR and the correct NEP1-40 was confirmed by
      sequencing. Recombinant lentiviruses were produced in 293T cells after the
      cotransfection of pGC-FU-NEP1-40, and packaging plasmids of pHelper 1.0 and
      pHelper 2.0. Green fluorescent protein (GFP) expression of infected 293T cells
      was observed to evaluate gene delivery efficiency. NEP1-40 protein expression in
      293T cells was detected by Western blot. RESULTS: The lentiviral expression
      vector carrying NEP1-40 was successfully constructed by GFP observation, and NEP1
      40 protein expression was detected in 293T cells by Western blot. CONCLUSION: The
      recombinant lentivirus pGC-FU-NEP1-40 is successfully constructed and it lays a
      foundation for further molecular function study of NEP 1-40.

PMID- 22403881
TI  - [Cellular therapy of stress urinary incontinence].
AB  - OBJECTIVE: To review the progress and clinical application of cellular therapy
      for stress urinary incontinence (SUI). METHODS: The literature about cellular
      therapy of SUI was extensively reviewed. RESULTS: Because of having no or poor
      regeneration capacity, the clinical application of chondrocytes and myoblasts
      were limited. Based on the rapid progress in stem cell biology, an increasing
      number of animal experiments and clinical trials about cellular therapy of SUI
      have been reported with encouraging results. All these show that cellular therapy
      has great potential in clinical application. Stem cells are considered as ideal
      seeded-cells for treatment of SUI. CONCLUSION: Cellular therapy, especially stem
      cells, provides a novel approach for treatment of SUI, but the mechanism needs
      further study.

PMID- 22403882
TI  - [Transplantation of neural stem cells and bone marrow mesenchymal stem cells in
      treatment of spinal cord injury].
AB  - OBJECTIVE: To review the progress in the treatment of spinal cord injury (SCI) by
      graft of neural stem cells (NSCs) or bone marrow mesenchymal stem cells (BMSCs)
      as well as immune characteristics of two stem cells. METHODS: Different kinds of
      documents were widely collected, and then immunologic characteristics of NSCs and
      BMSCs were summarized. The therapy of SCI by stem cell transplantation was
      reviewed. Additionally, some problems in treatment were analyzed. RESULTS:
      Experimental study showed that graft of NSCs and BMSCs can promote the functional
      recovery of the injured spinal cord in animals. Due to immunologic properties of
      two stem cells, rejection reaction of transplantation could produce a harmful
      effect on SCI treatment. CONCLUSION: Transplantation of NSCs or BMSCs might be an
      effective measure for SCI treatment, but immunologic rejection reaction must be
      considered.

PMID- 22403883
TI  - [Vancomycin cationic liposome combined with nano-hydroxyapatite/chitosan/konjac
      glucomannan scaffold for treatment of infected bone defects in rabbits].
AB  - OBJECTIVE: To investigate the anti-infection and bone repair effects of cationic
      liposome-encapsulated vancomycin combined with the nano
      hydroxyapatite/chitosan/konjac glucomannan (n-HA/CS/KGM) composite scaffold in
      vivo. METHODS: Fifty-one 6-month-old New Zealand white rabbits, weighing 1.5-3.0
      kg, were selected to prepare chronic infectious tibia bone defect model by using
      Staphylococcus aureus. After 4 weeks, 48 survival rabbits were randomly divided
      into 4 groups (n=12). After debridement, defect was treated with nothing in group
      A, with n-HA/CS/KGM composite scaffold in group B, with vancomycin and n
      HA/CS/KGM composite scaffold in group C, and with cationic liposome-encapsulated
      vancomycin and n-HA/CS/KGM composite scaffold in group D. After 8 weeks of
      treatment, general observation, X-ray, HE staining, the bacterial culture, and
      the measurement of the longest diameter of bone defect were done. RESULTS: At 4
      weeks after modeling, 48 rabbits were diagnosed as having osteomyelitis,
      including periosteal new bone formation, destruction of bone, and soft tissue
      swelling. The Norden score was 3.83 +/- 0.52. At 8 weeks after treatment, sinus
      healed in groups C and D, but sinus was observed in groups A and B; the gross
      bone pathological scores of group D were significantly better than those of
      groups A and B (P < 0.05). Bone defects were repaired completely in group D, the
      results of the longest diameter of bone defects in group D was significantly
      better than those in the other 3 groups (P < 0.05). New bone formation was
      observed in groups C and D, but periosteal reaction and marrow low-density shadow
      were observed in groups A and B; Norden score in group D was significantly better
      than those in groups A, B, and C (P < 0.05). HE staining showed that there were a
      large number of trabecular bone formation and fibrosis, with no obvious signs of
      infection in groups C and D, but neutrophil accumulation was observed in groups A
      and B; Smeltzer scores in groups C and D were significantly better than those in
      groups A and B (P < 0.05). Bacteriological results showed higher negative rate in
      groups C and D than in groups A and B (P < 0.05). CONCLUSION: Cationic liposome
      encapsulated vancomycin and n-HA/CS/KGM composite scaffold can be a good
      treatment for infectious bone defects in rabbits, providing a new strategy for
      the therapy of bone defects in chronic infection.

PMID- 22403884
TI  - [Clinical application of pedicle screw fixation under guidance of computer
      assisted navigation in patients with osteoporosis].
AB  - OBJECTIVE: To study the effectiveness of computer assisted pedicle screw
      insertion in osteoporotic spinal posterior fixation. METHODS: Between December
      2009 and March 2011, 51 patients underwent pedicle screw fixation using the
      computer assisted navigation (navigation group), while 41 patients underwent the
      conventional technique (traditional group). All patients had osteoporosis under
      the dual-energy X-rays absorptiometry. There was no significant difference in
      age, gender, bone mineral density, involved segment, preoperative complications,
      and other general status between 2 groups (P > 0.05). The amount of blood loss,
      the operation time, the rate of the pedicle screw re-insertion, and the
      postoperative complication were observed. The state of the pedicle screw location
      was assessed by CT postoperatively with the Richter's classification and the
      fusion state of the bone graft was observed using three-dimensional (3-D) CT
      scans during follow-up. RESULTS: A total of 250 screws were inserted in
      navigation group, and 239 were inserted successfully at first time while the
      other 11 screws (4.4%) were re-inserted. A total of 213 screws were inserted in
      traditional group, and 190 were successful at first time while 23 screws (10.8%)
      were re-inserted. There was significant difference in the rate of screws re
      insertion between 2 groups (chi2 = 6.919, P = 0.009). Both the amount of blood
      loss and the operation time in navigation group were significantly less than
      those in traditional group (P < 0.05). According to Richter's classification for
      screw location, the results were excellent in 240 screws, good in 10 screws in
      navigation group; the results were excellent in 191 screws, good in 21 screws,
      and poor in 1 screw in traditional group. Significant difference was noticed in
      the screw position between 2 groups (chi2 = 7.566, P = 0.023). The patients were
      followed up (7.8 +/- 1.5) months in navigation group and (8.7 +/- 1.5) months in
      traditional group. No loosening, extraction, and breakage of the pedicle screw
      occurred in navigation group, and all these patients had successful fusion within
      6 months postoperatively. While in traditional group, successful fusion was shown
      in the other patients by 3-D CT, except the absorption of bone graft was found in
      only 1 patient at 6 months after operation. And then, after braking by adequate
      brace and enhancing the anti-osteoporotic therapy, the bone graft fused at 9
      months postoperatively. CONCLUSION: The computer assisted navigating pedicle
      screw insertion could effective reduce the deviation or re-insertion of the
      screws, insuring the maximum stability of each screw, mean while it can reduce
      the exposure time and blood loss, avoiding complication. The computer assisted
      navigation would be a useful technique which made the pedicle screw fixation more
      safe and stable in patients with osteoporosis.

PMID- 22403885
TI  - [Triple endobutton technique for repair of chronic complete acromioclavicular
      joint dislocations].
AB  - OBJECTIVE: To evaluate the early result of triple Endobutton technique for
      reconstructing coracoclavicular ligament of chronic complete acromioclavicular
      joint dislocations. METHODS: Between January 2009 and June 2010, 14 patients with
      chronic complete acromioclavicular joint dislocations were treated with triple
      Endobutton technique for reconstructing coracoclavicular ligament. There were 10
      males and 4 females with a mean age of 38.5 years (range, 26-52 years). Injury
      was caused by traffic accident in 7 cases, by falling in 5 cases, and by bruise
      in 2 cases. The average time was 47 days from injury to the operation (range, 29
      75 days). All patients had pain and activity restriction. The X-ray films showed
      complete dislocation of acromioclavicular joint. According to Allman's type, all
      cases were classified as III degree complete dislocations. RESULTS: At
      postoperation, wound healed by first intention with no early complication of
      infection or neurovascular injury. All patients were followed up 18.3 months on
      average (range, 13-30 months). Acromioclavicular joint subluxation occurred in 1
      patient at 1 week after operation, and no redislocation or other complication
      occurred in the other patients. American Shoulder and Elbow Surgeons (ASES) score
      was 90.8 +/- 4.1 at last follow-up, showing significant difference when compared
      with the preoperative score (65.3 +/- 4.4) (t = -17.57, P = 0.00); Constant
      Murley score was 91.7 +/- 3.9, showing significant difference when compared with
      preoperative one (71.5 +/- 4.6) (t = -75.02, P = 0.00). The definite answer in
      Simple Shoulder Test (SST) averaged 9.7 (range, 7-12). CONCLUSION: The triple
      Endobutton technique for reconstructing coracoclavicular ligament is an effective
      method in treatment of chronic complete acromioclavicular joint dislocations. The
      short-term results are satisfactory.

PMID- 22403886
TI  - [Effectiveness analysis of artificial humeral head replacement for 18 cases of
      complicated fractures of the proximal humerus].
AB  - OBJECTIVE: To evaluate the effectiveness of artificial humeral head replacement
      in treatment of complicated fractures of the proximal humerus. METHOD: Between
      January 2005 and January 2011, 18 patients with proximal humerus fracture were
      treated with artificial humeral head replacement. There were 8 males and 10
      females with a mean age of 71 years (range, 52-84 years). Fractures were caused
      by falling in 11 cases, by traffic accident in 3 cases, and by bruise in 4 cases.
      The time between injury and admission was 2 hours to 3 days (mean, 1.5 days).
      According to Neer classification, 8 cases had three-part fracture, 7 four-part
      fracture, and 3 cleavage fracture of humeral head; 5 cases complicated by
      shoulder joint subluxation, 2 cases by femoral fracture, 1 case by radial
      fracture, and 11 cases by osteoporosis. All the patients were treated with
      modular cemented prostheses. RESULTS: The operation time was 60-180 minutes with
      an average of 80 minutes; the blood loss was 100-400 mL with an average of 200
      mL. All incisions healed by first intention without infection or neurovascular
      injury. Sixteen patients were followed up 3 years on average (range, 1-6 years).
      No loosening, dislocation of prosthesis or heterotopic ossification occurred.
      According to the Neer scores, the results were excellent in 5 cases, good in 8
      cases, moderate in 2 cases, and poor in 1 case at 1 year after operation. The
      excellent and good rate was 81.2%. CONCLUSION: Artificial humeral head
      replacement is a good therapy for patients with complicated fractures of the
      proximal humerus, especially for elderly patients.

PMID- 22403887
TI  - [Arthroscopic poking reduction and internal fixation of radial head fractures].
AB  - OBJECTIVE: To investigate the methods and effectiveness of arthroscopic poking
      reduction and percutaneous fixation of radial head fractures. METHODS: Between
      August 2002 and May 2010, 15 patients with radial head fractures were treated
      using arthroscopic poking reduction and percutaneous fixation with a Kirschner
      wire. There were 11 males and 4 females with an average age of 29.6 years (range,
      17-41 years). The locations were left side in 6 cases and right side in 9 cases.
      Injuries were caused by falling in 8 cases, by traffic accident in 4 cases, and
      by sports in 3 cases. The average time from injury to admission was 3.4 days
      (range, 1-8 days). Of them, 13 patients had Mason type II, and 2 patients had
      type III fractures. Accompanying injuries were lateral collateral ligament
      ruptures in 5 patients. RESULTS: The X-ray films confirmed good reduction and
      fracture healing. Incisions healed by first intention; no complication occurred,
      such as neurovascular injury, infection, or hardware failure. All patients were
      followed up 25 months on average (range, 12-32 months). The flexion-extension arc
      was (139.0 +/- 7.9) degrees at last follow-up, showing no significant difference
      when compared with the contralateral (141.0 +/- 5.1) degrees (t = 1.146, P =
      0.271); the range of pronation and supination was (143.3 +/- 7.0) degrees when
      compared with the contralateral (146.0 +/- 4.7) degrees (t = -1.948, P = 0.072).
      The mean Mayo elbow performance score was 92 (range, 80-100); the mean Broberg
      Morrey score was 95.2 (range, 85-100); the results were excellent in 12 cases and
      good in 3 cases. CONCLUSION: Arthroscopic poking reduction and percutaneous
      fixation with a Kirschner wire offers accurate reduction, reliable fixation,
      minimal trauma, rapid recovery, and lower morbidity for Mason type II and
      selective Mason type III radial head fractures.

PMID- 22403888
TI  - [Treatment of postoperative nonunion of fracture of lower limb with bone grafting
      by intervertebral disc endoscope].
AB  - OBJECTIVE: To explore the effectiveness of bone grafting by intervertebral disc
      endoscope for postoperative nonunion of fracture of lower limb. METHODS: Between
      August 2004 and August 2008, 40 patients (23 males and 17 females) with
      postoperative nonunion of femoral and tibial fracture, aged 20-63 years (mean,
      41.5 years) were treated. Nonunion of fracture occurred at 10-16 months after
      internal fixation. During the first operation, the internal fixation included
      interlocking intramedullary nailing of femoral fracture in 12 cases and plate in
      16 cases, and interlocking intramedullary nailing of tibial fractures in 9 cases
      and plate in 3 cases. The X-ray films showed hypertrophic nonunion in 24 cases,
      common nonunion in 3 cases, and atrophic nonunion in 13 cases. RESULTS: The
      average operation time was 61 minutes (range, 40-80 minutes), and the blood loss
      was 80-130 mL (mean, 100 mL). The hospitalization time were 6-11 days (mean, 8.1
      days). Incisions healed by first intention in all patients with no complication
      of infection or neurovascular injury. Forty patients were followed up 10-16
      months (mean, 12.3 months). The X-ray films showed that all patients achieved
      healing of fracture after 4-10 months (mean, 6.8 months). No pain, disfunction,
      or internal fixation failure occurred. CONCLUSION: Bone grafting by
      intervertebral disc endoscope is an effective method for treating postoperative
      nonunion of femoral and tibial fracture.

PMID- 22403889
TI  - [Free tissue transplantation from amputated limbs for covering raw surface of
      stumps].
AB  - OBJECTIVE: To investigate and evaluate the effectiveness of covering amputated
      raw surface with free tissue transplantation from damaged limbs. METHODS: Between
      August 2010 and June 2011, 5 cases of severe injury of lower extremities were
      treated, including 4 males and 1 female with an age range of 3 years and 8 months
      to 43 years. Of them, 3 cases suffered from traffic accident injury and 2 had
      machine injury. The disease duration was 2-9 hours. Among the 5 cases, 1 suffered
      from half pelvis destruction and traumatic amputation of hip joint, 1 from
      comminuted open fracture of proximal femur, and another 3 from thigh destruction
      with survival soft tissue of legs. All cases were treated with emergency
      operation of amputation. The raw surface of the residual stumps was 20 cm x 10 cm
      to 20 cm x 20 cm in size. Two lateral anterior thigh flaps and 3 posterior tibial
      artery flaps were harvested from the damaged limbs. The flap size ranged from 15
      cm x 10 cm to 25 cm x 20 cm. The wounds were repaired with free tissue
      transplantation. RESULTS: Five transplanted tissue flaps were survival. Skin
      necrosis occurred in the wound edge at 7-10 days postoperatively and was cured
      after excision of necrotic tissue, dressing change or vacuumed drainage for 1-2
      months. All wounds healed and the patients were followed up 1-3 months. No sinus
      tract or ulceration was observed. The appearance of stumps was satisfactory.
      CONCLUSION: The effectiveness of repairing amputated raw surface with free tissue
      transplantation from amputated limbs is satisfactory. It is an effective
      procedure to repair the raw surface of amputated stumps.

PMID- 22403890
TI  - [Effectiveness evaluation of composite skin grafts in repairing deep burn wounds
      in functional regions].
AB  - OBJECTIVE: To evaluate the long-term effectiveness of composite grafts of
      acellular dermal matrix (ADM) and autologous split-thickness skin in repairing
      deep burn wounds. METHODS: Between June 2002 and December 2008, 30 patients (42
      wound) were treated. There were 25 males and 5 females, aged 3-52 years with a
      median age of 31 years. Of them, 24 burned patients had 35 wounds, including 23
      deep second degree and 12 third degree wounds with a mean disease duration of 24
      days (range, 3-45 days); 6 patients with hyperplastic scar had 7 wounds with a
      mean disease duration of 16 days (range, 9-21 days). The wound locations were
      neck (2 wound), hand (4 wounds), forearm and elbow (8 wounds), shoulder (3
      wounds), peoples (6 wounds), laps (4 wounds), ankle and legs (15 wounds), and the
      area of wounds ranged from 10 cm x 10 cm to 30 cm x 20 cm. After thorough
      debridement, tangential excision, and scar excision, ADM and autologous split
      thickness skin graft were used to repair the wounds by one-step method. RESULTS:
      After operation, composite skin graft survived completely in 39 wounds of 27
      patients, with a survival rate of 92.9%; partial necrosis occurred in 3 wounds of
      3 patients (7.1%), and healed after dressing change and secondary skin graft. The
      patients were followed up 30-34 months (mean, 32 months) postoperatively. The
      appearance of the composite grafts were smooth and soft with good elasticity and
      low pigmentation. The activity and function of limbs recovered well. No scar
      hyperplasia was observed at the donor sites. CONCLUSION: It can achieve good
      outcomes in appearance and function to use ADM and autologous split-thickness
      skin graft for repairing deep burn wounds in functional regions.

PMID- 22403891
TI  - [Repair of face and upper limb defects with expanded delto-pectoral and abdominal
      perforator flaps].
AB  - OBJECTIVE: To investigate the method and effectiveness of expanded delto-pectoral
      and abdominal perforator flaps in repairing large defects of the face and upper
      limb after scar excision. METHODS: Between August 2000 and February 2011, 25
      patients with large scars on face and upper limb were treated. There were 14
      males and 11 females with an average age of 27 years (range, 7-36 years). Scars
      causes were burn and scald in 25 cases with a disease duration of 6 months to 7
      years (mean, 4.5 years). The hypertrophic scars located at face in 15 cases, and
      at upper limb and hand in 10 cases. The soft tissue expanders (300-500 mL in
      volume) were implanted in the delto-pectoral zone and abdominal region in one
      stage operation. In two-stage operation, after scars were resected, defects (9 cm
      x 7 cm to 17 cm x 8 cm) were repaired with the delto-pectoral perforator flaps
      (17 cm x 7 cm to 20 cm x 8 cm) in 15 facial scar cases and with the deep inferior
      epigastric artery perforator flaps (10 cm x 9 cm to 25 cm x 14 cm) in 10 upper
      limb and hand scar cases. The donor sites were sutured directly. RESULTS: Partial
      necrosis of the flaps occurred in 2 cases after operation, then the flap survived
      after expectant treatment. The other flaps and skin grafts survived successfully,
      and the incisions healed by first intention. Ten patients were followed up 6
      months to 4 years. The appearance, texture, and color of the flaps were similar
      to those at the donor site. CONCLUSION: It is an effective method to use the
      delto-pectoral perforator flap and the deep inferior epigastric artery perforator
      flap for repairing soft tissue defects of the face and upper limb after scar
      excision.

PMID- 22403892
TI  - [Treatment of adult congenital muscular torticollis by multiple
      sternocleidomastoid head amputation].
AB  - OBJECTIVE: To investigate the therapeutic method and effectiveness of multiple
      sternocleidomastoid head amputation for adult congenital muscular torticollis.
      METHODS: Between March 2009 and February 2011, 19 patients with congenital
      muscular torticollis were treated with multiple sternocleidomastoid head
      amputation. There were 13 males and 6 females, aged 16-32 years (mean, 23.5
      years). The X-ray films showed that 12 cases were accompanied with some extent
      cervical lateral bending and wedge change. Ten patients were with ipsilateral
      facial bradygenesis. Four patients had received single sternocleidomastoid head
      amputation. All of the 19 patients were treated with multiple sternocleidomastoid
      head amputation, then plaster support and neck collar were used after operation
      for 3-6 months. RESULTS: The wounds of all the 19 patients healed primarily,
      without infection or hematoma. Sixteen patients were followed up 5 months to 2
      years (mean, 8 months). The head and neck malformations were ameliorated
      significantly. The effectiveness was assessed 2 weeks later, in 7 patients
      without cervical vertebral malformation results were excellent; in 12 patients
      with cervical vertebral malformation, the results were excellent in 1 case, good
      in 7 cases, and fair in 4 cases. The length between mastoid process and
      sternoclavicular joints was elongated (1.88 +/- 0.30) cm significantly after
      operation in patients without cervical vertebral malformation (t = 6.24, P =
      0.00), showing no significant difference when compared with normal value (t =
      1.87, P = 0.11); the length was elongated (3.38 +/- 0.30) cm significantly (t =
      11.37, P = 0.00) after operation in patients with cervical vertebral
      malformation, but it was significant shorter than normal value (t = 12.19, P =
      0.00). CONCLUSION: Multiple sternocleidomastoid head amputation is a safe and
      effective method for adult congenital muscular torticollis, which can improve the
      neck rotation function.

PMID- 22403893
TI  - [Temporary intravascular shunts for quick restoration of perfusion to the
      extremity with major vascular injury].
AB  - OBJECTIVE: To report clinical experience in the use of temporary intravascular
      shunts (TIVS) for quick restoration of perfusion to the extremity with major
      vascular injury. METHODS: Between August 2009 and March 2011, TIVS was applied
      temporarily to restore blood perfusion to the extremity in 6 patients with major
      extremity vascular structure injury secondary to trauma (4 patients) or tumor
      resection (2 patients), who would received vascular transplantation and underwent
      long ischemia. The patterns of vascular shunts included external carotid artery
      subclavian artery, axillary artery-axillary artery, axillary vein-subclavian
      vein, brachial artery-brachial artery, brachial vein-brachial vein, brachial
      artery-radial artery, femoral artery-popliteal artery, and popliteal artery
      posterior tibial artery. After TIVS, extensive debridement, fracture fixation, or
      tumor excision was performed. Then the shunted tubes were removed, and the
      vessels were repaired definitely. Six vessels were repaired by transplanting the
      great saphenous veins; one vessel was anastomosed directly without tension; and
      one vessel was repaired by artificial vascular graft. RESULTS: All shunted tubes
      were successfully established within 5 to 10 minutes (mean, 8.2 minutes). The
      duration of bypass ranged from 67 to 210 minutes. After establishment of TIVS,
      blood perfusion to the affected limb was improved. When shunted tubes were
      removed, thrombosis and partial obstruction occurred in one who accepted
      amputation, and the others kept patency. No loosening of tubes and haemorrhage
      occurred. At 2-15 months of follow-up, affected limbs had good blood supply.
      CONCLUSION: TIVS is rapid and simple, which can quickly restore blood perfusion
      to the extremity with major vascular injury and shorten the ischemic time of the
      affected extremity.

PMID- 22403894
TI  - [Anatomical study on contralateral C7 nerve transfer via posterior spinal route
      for treatment of brachial plexus root avulsion injury].
AB  - OBJECTIVE: To investigate the feasibility of contralateral C7 nerve transfer via
      posterior spinal route for treatment of brachial plexus root avulsion injury by
      anatomical study. METHODS: Ten cadaveric specimens of 7 men and 3 women were
      selected, who had no obvious deformity and no tissue defect in neck neutral
      position. By simulating surgical exploration of brachial plexus injury, the
      length of contralateral C7 nerve root was elongated by dissecting its anterior
      and posterior divisions to the distal end, while the length of C7 nerve from the
      intervertebral foramen to the branching point and the length of the anterior and
      posterior divisions were measured. By simulating cervical posterior approach, the
      C7 vertebral plate and T1 spinous process were fully exposed; the hole was made
      near vertebral body; and the C7 nerve root lengths by posterior vertebra path to
      the contralateral upper trunk and lower trunk were measured. RESULTS: C7 nerve
      root length was (58.62 +/- 8.70) mm; the length of C7 nerve root plus posterior
      or anterior division was (65.15 +/- 9.11) mm and (70.03 +/- 10.79) mm,
      respectively. By posterior spinal route, the distance was (72.12 +/- 10.22) mm
      from the end of C7 nerve to the contralateral upper trunk of brachial plexus, and
      was (95.21 +/- 12.50) mm to the contralateral lower trunk of brachial plexus.
      CONCLUSION: Contralateral C7 nerve can be transferred to the contralateral side
      through posterior spinal route and it only needs short bridge nerve or no. The
      posterior spinal route can effectively prevent from neurovascular injury, so it
      might be the best surgery approach for the treatment of brachial plexus root
      avulsion injury.

PMID- 22403895
TI  - [Current development of correction of severe and rigid scoliosis].
AB  - OBJECTIVE: To summarize the current development of the correction of severe and
      rigid scoliosis. METHODS: Recent literature concerning the correction of severe
      and rigid scoliosis at home and abroad was extensively reviewed, and current
      developments of the correction of severe and rigid scoliosis were summarized.
      RESULTS: The correction of severe and rigid scoliosis shows developments as
      follows: the application of Halo-gravity traction increase and Halo-femoral
      traction is applied in posterior correction surgery. Fixation and correction
      technique with all pedicle screws was gradually popularized. The applications of
      posterior vertebral column resection, one-stage anterior and posterior surgery,
      and posterior-only correction surgery increase. CONCLUSION: The developments of
      all kinds of correction techniques improve the correction effects of severe and
      rigid scoliosis. Now there is no standardized treatment protocol for severe and
      rigid scoliosis. Greater development can be expected in the future

PMID- 22403896
TI  - [Application of porous tantalum implant in treatment of bone defect].
AB  - OBJECTIVE: To review the progress in the treatment of bone defect by porous
      tantalum implant. METHODS: Recent literature was extensively reviewed and
      summarized, concerning the treatment method of bone defect by porous tantalum
      implant. RESULTS: By right of their unique properties, porous tantalum implants
      have achieved very good results in the treatment of certain types of bone
      defects. CONCLUSION: Porous tantalum implants have their own advantages and
      disadvantages. If the case is meet to its indications, this method can obtain a
      good effect. Porous tantalum implants provide a new way for the clinical
      treatment of bone defects.

PMID- 22403897
TI  - Let's focus on resilience, as well as risks.

PMID- 22403898
TI  - The potential contribution of mentor programs to relational permanency for youth
      aging out of foster care.
AB  - This article summarizes published research regarding the effectiveness of mentor
      programs in general, and for youth in foster care specifically, as a basis for
      evidence-based practice in child welfare. It examines the pros and cons of mentor
      programs and characteristics of programs that are more or less effective for
      achieving specific social goals. The author explores the opportunity cost of
      investments in transitional mentor programs versus efforts to find permanent
      parents for youth aging out of care, and concludes with practice and policy
      implications of these findings.

PMID- 22403899
TI  - Diagnosis and medication overload? A nurse review of the psychiatric histories of
      older youth in treatment foster care.
AB  - Prior research has raised concern about the appropriateness of psychotropic
      medication use and the validity of psychiatric diagnosing for youth in child
      welfare but has lacked in-depth case information. This study reports results from
      a psychiatric nurse review conducted with eight youth entering a foster care
      intervention using case records and multiple key informant interviews. Results
      revealed extensive histories of unique (nonoverlapping) psychiatric diagnoses (M
      = 8, range 7-9) and past psychotropic medications (M = 13, range 9-21). The
      findings highlight the need to improve assessment practices and to create
      mechanisms that promote greater continuity of psychiatric care.

PMID- 22403900
TI  - What do we know about drug-endangered children when they are first placed into
      care?
AB  - Although the methamphetamine epidemic in the United States has caught the
      attention of law enforcement and the media, the needs of the children living in
      so-called "meth homes" have not yet been addressed. These children are endangered
      from not only the chemicals involved, but also parental abuse and/or neglect.
      Little is known, however, about how drug-endangered children are faring. This
      article summarizes the levels of health and well-being of drug-endangered
      children at the time they were removed from meth homes. Differences between
      children whose parents use meth and whose parents use other drugs are noted.
      Overall, the subjects are a highly traumatized, troubled, developmentally delayed
      group of very young children.

PMID- 22403901
TI  - Internalizing symptoms linking youths' maltreatment and delinquent behavior.
AB  - This study examines internalizing mental health symptoms (depression and
      posttraumatic stress disorder) as potential intervening factors in the
      relationship between maltreatment and delinquency using data from the National
      Survey for Child and Adolescent Well-Being (N = 1179). Significant mediating
      effects indicated that youth at greater risk of maltreatment experienced higher
      levels of internalizing symptoms that result in increased risk for delinquent
      behavior, although longitudinal effects were not supported. These findings
      highlight internalizing mental health symptoms as an important factor to address
      in treating victimized children at risk of future delinquency. Implications for
      child welfare service provision are discussed.

PMID- 22403902
TI  - Child fatality review teams: a content analysis of social policy.
AB  - Child fatality review teams (CFRTs) have existed since the 1970s; yet, a
      comprehensive understanding of their procedures, practices, and outcomes is
      lacking. This article addresses that gap in this study of CFRT state statutes.
      Findings indicate CFRT laws address nine areas of practice, from team
      composition, to purpose, to outcomes. Results also indicate that laws address
      prevention three times as often as investigation, but that both areas are related
      to state crime rates.

PMID- 22403903
TI  - State capacity: the missing piece in child welfare privatization.
AB  - Privatization has been used to address the limited capacity of government to
      achieve positive results in child welfare systems. Privatized systems have not
      realized better outcomes than their public counterparts, however, and many states
      continue to struggle with implementation. In order to demonstrate that
      privatization is in fact an investment on the part of the state, rather than a
      solution to limited public resources, this article explores the relationship
      between state capacity and privatization and makes recommendations for more
      effective partnerships between the public and private sectors.

PMID- 22403904
TI  - The crisis and fiscal policies in the peripheral countries of the Eurozone.
AB  - This article explains the political causes of the current financial crisis of the
      eurozone peripheral countries (Spain, Greece, Portugal, and Ireland) and how the
      crisis affects their welfare states. It examines how their profoundly
      conservative governments (dictatorships in Spain, Portugal, and Greece and
      authoritarian regime in Ireland) during the post-World War II period and the
      dominance of their states by right-wing forces have made these countries very
      vulnerable to the speculations of the financial markets.

PMID- 22403905
TI  - The other side of the Chinese economic miracle.
AB  - Despite the financial crisis still sinking the world economy, China's GDP growth
      rate in 2010 reached 10 percent, continuing the great momentum maintained since
      the 1980s. This is often referred to as the Chinese economic miracle. While many
      marvel at and try to mystify the miracle, the other side of the miracle is less
      than miraculous. Compared with the period of its planned economy between the
      1950s and 1970s, in the ensuing three decades, China has undergone slower
      progress in major health indicators, and this has been accompanied by an ailing
      health care system. This report presents a portrait of China's underdevelopment
      of health and its health care system, with up-to-date statistics. Such
      information is important for a fuller, more balanced, and more accurate view of
      the Chinese economic miracle.

PMID- 22403906
TI  - Debate on the Chernobyl disaster: on the causes of Chernobyl overestimation.
AB  - After the Chernobyl accident, many publications appeared that overestimated its
      medical consequences. Some of them are discussed in this article. Among the
      motives for the overestimation were anti-nuclear sentiments, widespread among
      some adherents of the Green movement; however, their attitude has not been wrong:
      nuclear facilities should have been prevented from spreading to overpopulated
      countries governed by unstable regimes and regions where conflicts and terrorism
      cannot be excluded. The Chernobyl accident has hindered worldwide development of
      atomic industry. Today, there are no alternatives to nuclear power: nonrenewable
      fossil fuels will become more and more expensive, contributing to affluence in
      the oil-producing countries and poverty in the rest of the world. Worldwide
      introduction of nuclear energy will become possible only after a concentration of
      authority within an efficient international executive. This will enable
      construction of nuclear power plants in optimally suitable places, considering
      all sociopolitical, geographic, geologic, and other preconditions. In this way,
      accidents such as that in Japan in 2011 will be prevented.

PMID- 22403907
TI  - Debate on the Chernobyl disaster: response to Dr. Sergei V. Jargin.
AB  - The author responds, point by point, to Dr. Jargin's critique in this Journal
      issue of A. V. Yablokov, V. B. Nesterenko, and A. B. Nesterenko, Chernobyl:
      consequences of the catastrophe for people and the environment, published in 2009
      by the New York Academy of Sciences.

PMID- 22403908
TI  - Debate on the Chernobyl disaster: response to Dr. Sergei V. Jargin.
AB  - The stated purpose of Chernobyl: Consequences of the Catastrophe for People and
      the Environment, published by the New York Academy of Sciences in 2009, was to
      challenge and answer publications on Chemobyl and its aftermath by the World
      Health Organization (WHO) and the International Atomic Energy Agency (IAEA).
      Until the independence of the WHO from the IAEA is assured, we can have little
      faith in their statements, whether it involves Chernobyl or Fukushima.

PMID- 22403909
TI  - An unexpected mortality increase in the United States follows arrival of the
      radioactive plume from Fukushima: is there a correlation?
AB  - The multiple nuclear meltdowns at the Fukushima plants beginning on March 11,
      2011, are releasing large amounts of airborne radioactivity that has spread
      throughout Japan and to other nations; thus, studies of contamination and health
      hazards are merited. In the United States, Fukushima fallout arrived just six
      days after the earthquake, tsunami, and meltdowns. Some samples of radioactivity
      in precipitation, air, water, and milk, taken by the U.S. government, showed
      levels hundreds of times above normal; however, the small number of samples
      prohibits any credible analysis of temporal trends and spatial comparisons. U.S.
      health officials report weekly deaths by age in 122 cities, about 25 to 35
      percent of the national total. Deaths rose 4.46 percent from 2010 to 2011 in the
      14 weeks after the arrival of Japanese fallout, compared with a 2.34 percent
      increase in the prior 14 weeks. The number of infant deaths after Fukushima rose
      1.80 percent, compared with a previous 8.37 percent decrease. Projecting these
      figures for the entire United States yields 13,983 total deaths and 822 infant
      deaths in excess of the expected. These preliminary data need to be followed up,
      especially in the light of similar preliminary U.S. mortality findings for the
      four months after Chernobyl fallout arrived in 1986, which approximated final
      figures.

PMID- 22403910
TI  - Wealth and well-being, economic growth, and integral development.
AB  - This essay tackles a bimillenary problem in psychology, ethics, economics, and
      political philosophy: that of the relations between wealth and well-being. What
      are they, and should we live for pleasure, or rather seek to live a full and
      useful life? This is the ancient dilemma between hedonism, the cult of pleasure,
      and eudemonism, the search for a good life. Economists, almost without exception,
      have opted for hedonism, but they have not found out what percentage of the goods
      that ordinary people want are not merchandises. This gap is currently being
      filled by psychologists, sociologists, socioeconomists, and other workers in the
      new "science of happiness". Their main finding, that happiness is not for sale,
      might surprise the orthodox economists. On the social level, the former problem,
      concerning individuals, gets translated into the question of national
      development: what kind of development should we seek, and for whom? In
      particular, should economic growth be prioritized, or should we promote the
      simultaneous development of all sectors of society, including the political and
      cultural? In either case, should development benefit the chosen few or everybody?
      And should it enhance the well-being of the individual and make that of her
      offspring possible? This problem, of course, lies at the intersection of three
      sciences--psychology, economics, and political science--and two chapters of
      philosophy--ethics and political philosophy. Consequently, anyone daring to
      propose original solutions to the problem in question will risk being criticized
      by experts distributed among these five fields, who are not used to talking to
      one another.

PMID- 22403911
TI  - The Cuban experience in public health: does political will have a role?
AB  - The role of political will in public health has been largely ignored. In Cuba,
      however, for the past 50 years, political will has been the ultimate,
      encompassing intersectoral action in public health. The excellent achievements in
      population health in Cuba during these 50 years have been widely recognized.
      Researchers have sought to explain this "Cuban paradox" by focusing on a large
      array of public health factors, including health promotion, primary care
      activities, and intersectoral action on health determinants. These factors
      constitute necessary but not sufficient conditions to achieve good health
      outcomes. This article defines political will and uses the experience of Cuba to
      illustrate the potential role of political will in public health. The authors
      suggest a framework for the evaluation of political will aimed at achieving good
      health, examining the "Five R's of political will," five observable features that
      may provide systematic information on the direction and realization of political
      will: (1) renewal of commitment, (2) reform of the system, (3) resource
      development, (4) review of performance, and (5) responsible management. These
      five features focus the spotlight on the consistency between health goals and
      public discourse and action.

PMID- 22403912
TI  - The reformist triad and institutional forgetting of culture: a field study into
      twentieth-century Swedish social medicine.
AB  - Social medicine deals with the interplay between medicine and society. An
      awareness of how analytical categories have emerged historically can strengthen
      the role the discipline can play in the societal reinventions of health care now
      under way around the world. This study examines the categories that informed
      social medicine in Sweden during the 20th century. An anthropological field study
      was conducted over a 12-year period in a Swedish academic clinical setting.
      Historical documents were used to link local-level issues with macro-level (here,
      national and European) contexts. Social medicine, modernity, and social democracy
      were found to share a common history and a common vision of what society should
      be. As a result, concepts from politics, ideology, economy, and science tended to
      be conflated. As a clinician at the study site explained, "samhalle [community]
      is both society and state". The consequence for social medicine is that culture
      has become neglected as an analytical category. This institutional amnesia has
      strongly influenced how 21st century social medicine, in this region of the
      world, has defined itself and its interests. To return a cultural perspective to
      social medicine, a critical distance must be kept between the analyses the
      discipline undertakes and the prevailing societal ideologies.

PMID- 22403913
TI  - Who is driving Mexico's asbestos policy?
AB  - The publication of an article on the global asbestos industry in April 2011
      provided a fitting reminder of the contradictory forces engaged in the
      international struggle over asbestos. In his essay, author James Rice wrote:
      "Asbestos is now widely recognized as an occupational hazard and an ambient
      environmental contaminant....[Nevertheless] production and consumption appear to
      have stabilized and, indeed, have been increasing in recent years". A pertinent
      question to ask, and one often posed by ban-asbestos campaigners, is, why has the
      developing world seen an escalation of asbestos consumption in the face of ever
      more knowledge about the deadly risks associated with its use? After all, human
      beings have an extraordinary capacity to learn from their mistakes. A child who
      has burned his finger on an open flame will be wary of repeating the experience.
      Why, then, do governments, consumers, workers, and members of the public refrain
      from acting, when the dangers of not doing so are so widely known? The answer is
      to be found in the complex interaction of asbestos industry stakeholders,
      government officials, diplomatic representatives, politicians, and professional
      advisors; the dirty dealings engaged in by the global band of asbestos profiteers
      rival anything you will have read about "Big Tobacco". A good place to begin the
      unraveling of the industry's machinations is Mexico.

PMID- 22403914
TI  - Harmony in drug regulation, but who's calling the tune? An examination of
      regulatory harmonization in health Canada.
AB  - Harmonizing standards on drug regulation makes sense, but it must protect safety,
      ensure that only drugs that are truly effective are marketed, and protect a
      country's ability to act independently. The main driving force behind
      international harmonization is the International Conference on Harmonization
      (ICH). When it comes to safety, the ICH has been harmonizing to the lowest common
      denominator. Examples of harmonization indicate that industry priorities have
      influenced the direction that Health Canada has taken. Harmonization is also
      intimately tied in with the policy of smart regulation, changing regulations in a
      way that enhances the climate for investment. Canada has introduced user fees in
      concert with other countries, but there are concerns that these may compromise
      safety standards. When it comes to transparency, Health Canada has chosen to
      adopt the more restrictive European Union model rather than the more open process
      used by the United States. Finally, there are a number of areas in which Health
      Canada has chosen not to harmonize, and in each case the decision is in the
      direction of lower safety standards. Harmonization could be of benefit to Canada,
      but the evidence to date suggests that Health Canada been harmonizing down rather
      than up.

PMID- 22403915
TI  - In defiance of the evidence: conservatives threaten to "reform" away England's
      National Health Service.
AB  - David Cameron's Conservative-led coalition government is pressing ahead with a
      highly controversial bill to "reform" the National Health Service (NHS),
      abolishing existing management structures, opening up provider services to
      private competition from "any qualified provider", and establishing a competitive
      market system in place of planning. The proposals fragment the structures and run
      counter to the founding principles of the NHS, which in 1948 transcended the
      limitations of markets, delivering health care on the basis of maximum risk
      sharing and universal access to services, free at the point of use. Evidence
      shows markets are a costly and inadequate mechanism to deliver universal and
      comprehensive health care, and private providers will only bid for services where
      profits are guaranteed. Opposition to the proposals is strong among health
      professionals and informed opinion, and the bill has divided the coalition
      parties--but time is running out for those who reject the bill to mount a
      sustained and concerted resistance.

PMID- 22403916
TI  - Individual differences in sensitivity to violence.
AB  - A survey of university students explored correlates of sensitivity to violence,
      defined as a person's average rating of the severity of violence of several
      behaviors. The 79 women were somewhat more sensitive than the 39 men. Sensitivity
      was associated with the tendency to describe oneself as violence sensitive or
      violence tolerant, with the person's manner of defining the concept of violence,
      and with the tendency to include verbal abuse and inaction as possible forms of
      violence. Sensitivity was not clearly associated with some other variables, such
      as attitudes toward bullying and acceptability of hunting. The potential utility
      of measuring sensitivity to violence, and further work suggested by these
      findings, are discussed.

PMID- 22403917
TI  - The comparison of performances of preschool children on two motor assessments.
AB  - Understanding children's motor performance on different assessments is important
      for researchers. The Test of Gross Motor Development-2 (TGMD-2) and the Movement
      Assessment Battery for Children-2 (MABC-2) are motor assessments that use either
      a process- or product-oriented scoring approach. However, no studies have
      examined how performances are related to these two types of assessment. This
      study compared the performance of preschool children on the TGMD-2 and the MABC
      2. 32 children (M age = 4.2 yr., SD = 9) completed each test to assess whether
      each described motor performance similarly. Significant low to moderate
      Spearman's rank correlations (r2 range = .13-.40) were found between the
      subscales of the assessments. A related-samples Wilcoxon signed rank test was not
      significant between total performances on the TGMD-2 and MABC-2. From a practical
      standpoint, each assessment provides a similar overall description of motor
      competence in preschool children. However, each assessment results in scores that
      present different information about motor performance.

PMID- 22403918
TI  - Do university students really have difficulty in duration judgments? Comment on
      Okazaki and Matsuda (2008, 2010).
AB  - Reinterpretation suggests that low performance of the participants studied by
      Okazaki and Matsuda (2008, 2010) may have been caused by using a procedure which
      overloads the cognitive capacities of undergraduate students. The questions asked
      participants about their reasoning could have led to cognitive overload because
      they performed two tasks: judgment of movement duration and paying attention to
      what kind of knowledge should be used (alpha or beta). Some interpretations are
      offered referring to possible effects of training procedures for applying both
      kinds of knowledge.

PMID- 22403919
TI  - Recognition of tactile relief by children and adults.
AB  - This study was designed to compare tactile sensitivity of children and adults on
      printed target stimuli covering a wide range of elevations and requiring
      different resolutions. A recognition-relief task using 9 digits at 6 levels of
      elevation from a surface (0.5, 0.4, 0.3, 0.2, 0.1, and 0.05 mm) was presented to
      24 young adults and 24 children. As predicted, relief elevations as low as 0.05
      mm were recognized above chance. As predicted, children performed significantly
      more poorly than the adults on recognition at all elevations, although the
      difference increased as elevation increased. Adults performed significantly
      better than children on high-resolution digit 8, but there was no reliable age
      difference on low-resolution digit 1. Recognition difference between the high-
      and low-resolution digits decreased nonlinearly as elevation increased,
      irrespective of age. Overall, the findings support previous research indicating
      greater tactile sensitivity in adults than in children, but the superiority was
      moderated by the elevation and resolution requirements of the stimuli.

PMID- 22403920
TI  - Method of presentation and sex differences when using a revised figural drawing
      scale to measure body size estimation and dissatisfaction.
AB  - The present study examined whether a revision of the Gardner, Jappe, and Gardner
      (2009) BIAS-BD figural drawing scale gave more accurate estimations of body size
      estimation and body dissatisfaction than a prior version. It also examined
      whether the order of figure presentation led to differing values for body size
      estimation and body dissatisfaction. The revised BIAS-BD scale included a
      continuous line beneath 17 figural drawings ordered in either ascending or
      descending size. Results were compared with previous studies using the original
      scale in which the 17 figural drawings were presented in a random order and,
      additionally, with a method using an adjustable video image by which the
      participants estimated their perceived body size by adjusting the width of their
      static image. The scale was presented to 330 undergraduate university students,
      including 199 women and 131 men. Overall, compared to BMIs calculated from the
      participants' reports of their height and weight, men and women participants gave
      less accurate estimations of body size using the revised scale when compared to
      the original BIAS-BD scale and video methodology. Participants reported
      significantly less body dissatisfaction than with the original scale. There was
      no significant difference in body size estimation when the figures were presented
      in ascending or descending size. Body dissatisfaction was greater for women than
      men, and when the figures were presented in descending order. Methodological
      considerations for using figural drawing scales in body image research are
      discussed.

PMID- 22403921
TI  - Distance mitigates perceived threat.
AB  - It has previously been shown that distance mitigates the extent to which visual
      cues convey perceived threat. It was hypothesized that the visual cues of eye
      contact, sex, facial expression, and posture would all convey threat. It was
      further hypothesized that the effects of visual cues on the perception of threat
      would decrease with distance, but the extent of those decreases was unknown. In
      the present study, participants were exposed to images of people situated in a
      physical venue. The images were created to exhibit combinations of the levels of
      the four visual cues (yes or no for eye contact, male or female for sex, hostile
      or benign for facial expression, and hostile or benign for posture). Participants
      were given an opportunity to record how threatening the images of the people
      seemed to be. The results supported all a priori hypotheses regarding the effects
      of the visual cues. The results also generated estimates of the distances at
      which those visual cues ceased to convey threat.

PMID- 22403922
TI  - Phase of oral contraceptive cycle and endurance capacity of rowers.
AB  - Eight female rowers (M age = 21.0 yr., SD = 2.8), using a monophasic oral
      contraceptive pill, performed a 1-hr. rowing ergometer test (intensity: 70%
      VO2max) during the active-pill and non active-pill phases of the oral
      contraceptive cycle. No significant differences were found in mean energy
      expenditure, oxygen consumption, respiratory exchange ratio, and heart rate
      during the endurance test at the two phases of the oral contraceptive cycle. Mean
      energy expenditure rate, carbohydrate energy expenditure, lipid energy
      expenditure, and blood lactate during the test were not statistically
      significantly different among the cycle phases. In conclusion, there was no
      observed difference in substrate oxidation and blood lactate level during
      endurance rowing at different phases of the oral contraceptive cycle in these
      endurance-trained rowers. Endurance-trained female athletes on oral
      contraceptives should not worry about the possible differences in substrate
      oxidation during everyday training at different phases of the oral contraceptive
      cycle.

PMID- 22403923
TI  - Measuring procedural imitation aptitude in children: further validation of the
      Preschool Imitation and Praxis Scale (PIPS).
AB  - The Preschool Imitation and Praxis Scale (PIPS) was developed to measure bodily
      and procedural imitation aptitude in young children. However, the investigation
      of procedural imitation is more complex than that of bodily imitation. The
      procedural imitation tasks of the PIPS mainly consisted of unusual acts upon
      objects (for example, switching on a lamp in a toy animal with the forehead).
      This study assessed the suitability of these tasks by ruling out nonimitative
      learning in 15 typically developing children between 12 and 55 mo. of age (6
      girls, 9 boys). Results indicated that the tasks seem novel and unlikely to be
      performed spontaneously by the children. In addition, the number of target acts
      performed by the children in the imitation condition was significantly higher
      than in the baseline, investigator-manipulation, and imitation-enhancement
      nonimitative control conditions. Finally, the tasks elicited more frequently
      imitative behaviour than end-state emulation. Therefore, the tasks appear
      appropriate to measure procedural imitation, and the findings support the
      theoretical validity of the PIPS.

PMID- 22403924
TI  - Influence of background on precision of 3D depth judgment tasks in a real
      environment.
AB  - Presently, little is known about the effect of curved backgrounds against which
      the target stimulus is presented on precision in stereoacuity. The experiment
      analyzed the influence of stimulus orientation and 3D background configuration on
      stereoscopic vision. Participants were instructed to perform 3D visual alignment
      tasks on a modified version of the Howard-Dolman apparatus, whereupon precision
      in depth perception for different curved backgrounds (flat, black, concave, and
      convex) was evaluated. In addition, the influence of stimulus orientation (0
      degrees, 45 degrees, and 90 degrees) on precision was examined. The findings
      revealed an underestimation in the perceived depth in all background
      configurations, indicating highest and lowest precision outcomes for convex and
      concave backgrounds, respectively. In addition, a significant interaction of
      background and orientation was found. It was concluded that, in a real
      environment, background local depth cues are integrated with target stimuli to
      contribute to depth perception.

PMID- 22403925
TI  - Physiological profile of fighters influences training organisation in combat
      sports: response to Del Vecchio, Hirata, and Franchini (2011).
AB  - The article by Del Vecchio, et al. (2011) provides relevant information to
      trainers about the effort-pause ratio during mixed martial arts matches. Taking
      into account the physiological profiles of fighters would increase interest in
      these findings.

PMID- 22403926
TI  - Retroactive interference and mental practice effects on motor performance: a
      pilot study.
AB  - This study examined the effect of similar versus dissimilar retroactive
      interference on the mental practice effects for performing a novel motor skill.
      Research has shown that mental practice of a motor task can interfere with
      learning and performance of the task; however, little is known about how
      different retroactive interference activities affect mental practice effects. 90
      volunteers ages 18 to 51 years (M=26.8, SD=9.6) completed a pre-test and post
      test of 10 sets of five trials of a throwing task with the non-preferred hand. In
      the practice phase, participants mentally practiced the throwing task and then
      mentally practiced a task that was similar, dissimilar, or completed an unrelated
      reading task. Performance for all groups improved from pre- to post-test;
      however, there were no differences in increases for the three groups. The
      findings suggest that mental practice of similar and dissimilar tasks produced no
      significant interference in performance.

PMID- 22403927
TI  - Left-handedness in professional basketball: prevalence, performance, and
      survival.
AB  - Performance and handedness data were examined for 3,647 professional basketball
      players who participated in at least five games during the period between 1946
      and 2009. Left-handed players comprised 5.1% of all professional basketball
      players compared to the 11% prevalence in the general population. Left-handers
      had better performance averages, in terms of the number of points, rebounds, and
      blocks over their careers, as well as other measures, and had significantly
      longer careers than right-handed players. Handedness was not significantly
      related to mean or median life expectancy.

PMID- 22403928
TI  - Concurrent visual feedback and spatial accuracy in continuous aiming movements.
AB  - The effect of concurrent visual feedback (CVF) on continuous aiming movements was
      investigated in the preferred hand of participants of college age (ns = 12 men, 8
      women). Participants made continuous rapid reversal movements with a lightweight
      lever in the sagittal plane. Participants attempted to reach a short target (20
      degrees) and a long target (60 degrees) in separate constant practice conditions,
      but alternated between the two targets in a variable practice condition. Four
      blocks of practice trials were provided in each condition, with 40 movements made
      in each. CVF of the position-time trace was provided for the first 20 movements
      of each block, but was removed for the remaining 20 movements in each block.
      Movements were more accurate and consistent during constant practice compared to
      variable practice where the short target was overshot and the long target was
      undershot. CVF reduced errors in all conditions, compared to movements without
      CVF, particularly for the short target during variable practice. The results
      suggest that the interference generated by alternating targets can be modulated
      by providing visual feedback, but once the visual feedback was removed, errors
      increased markedly.

PMID- 22403929
TI  - Memory instructions, vocalization, mock crimes, and concealed information tests
      with a polygraph.
AB  - Accuracy rates with polygraphs using concealed information tests (CITs) depend on
      memory for crime details. Some participants read instructions on murdering a
      dummy victim that specified exact crime details asked on the subsequent CIT.
      Others read instructions not stating details, but still requiring interaction
      with the exact same details for the crime. For example, the murder weapon was
      under four heavy boxes. Instructions stated either "... remove the 4 boxes ..."
      or "... remove the boxes ..." Thus, each group removed four boxes, but only one
      group was primed with the number "4" beforehand. In addition, the victim
      unexpectedly shouted at some participants during the crime. An innocent group was
      not exposed to either manipulation. Memory, detection scores, and detection rates
      were lower for guilty participants not primed with details. Sound affected
      detection scores but not memory, and there was no interaction between the two
      factors. Information tests are limited by how crime information is received.

PMID- 22403930
TI  - The first 100 milliseconds of a face: on the microgenesis of early face
      processing.
AB  - Face recognition involves both processing of information relating to features
      (e.g., eyes, nose, mouth, hair, i.e., featural processing), as well as the
      spatial relation between these features (configural processing). In a sequential
      matching task, participants had to decide whether two faces that differed in
      either featural or relational aspects were identical or different. In order to
      test for the microgenesis of face recognition (the development of processing
      onsets), presentation times of the backward-masked target face were varied (32,
      42, 53, 63, 74, 84, or 94 msec.). To test for specific processing onsets and the
      processing of different facial areas, both featurally and relationally modified
      faces were manipulated in terms of changes to one facial area (eyes or nose or
      mouth), two, or three facial areas. For featural processing, an early onset for
      the eyes and mouth was at 32 msec. of presentation time, but a late onset for the
      nose was detected. For relationally differing faces, all onsets were delayed.

PMID- 22403931
TI  - Self-other rating agreement and leader-member exchange (LMX).
AB  - Data from a sample of 83 elected community leaders and 391 direct-report staffers
      (resulting in 306 useable leader-member dyads) were used to test relations
      between self-other rating agreement of leadership and member-reported leader
      member exchange (LMX). Results of polynomial regression analysis indicated that
      the self-other rating agreement model was not significantly related to member
      reported LMX. Instead, virtually all of the variance in member-reported LMX was
      accounted for by others' ratings.

PMID- 22403932
TI  - Interactive processing among parts, configuration, and orientation of complex
      objects.
AB  - The aim of the present study was to investigate whether the representation of
      parts and the configuration and orientation of complex objects were separate or
      interdependent. Participants were asked to match parts and configuration of novel
      3-D objects with constant or varied features in irrelevant dimensions. The
      results of both Exp. 1 (sequential matching) and Exp. 2 (simultaneous matching)
      showed that both sensitivity and response time (RT) of part matching were
      influenced by whether the irrelevant configuration remained constant or varied.
      Both sensitivity and RT for configuration matching were affected by the variation
      of irrelevant parts in Exp. 2, but only sensitivity was affected in Exp. 1. These
      results demonstrated an interdependent pattern of representations of parts and
      relations but different interactive patterns in memory and perception. The
      results of Exp. 3 showed orientation dependency in a configuration-matching task
      but orientation invariance in a part-matching task. Consistent with a study done
      in 2000 by Edelman and Intrator, these results suggest an interactive processing
      between configuration and orientation but an independent processing between the
      parts and orientation.

PMID- 22403933
TI  - Sensitivity to coincidences and paranormal belief.
AB  - Often it is difficult to find a natural explanation as to why a surprising
      coincidence occurs. In attempting to find one, people may be inclined to accept
      paranormal explanations. The objective of this study was to investigate whether
      people with a lower threshold for being surprised by coincidences have a greater
      propensity to become believers compared to those with a higher threshold.
      Participants were exposed to artificial coincidences, which were formally defined
      as less or more probable, and were asked to provide remarkability ratings.
      Paranormal belief was measured by the Australian Sheep-Goat Scale. An analysis of
      the remarkability ratings revealed a significant interaction effect between Sheep
      Goat score and type of coincidence, suggesting that people with lower thresholds
      of surprise, when experiencing coincidences, harbor higher paranormal belief than
      those with a higher threshold. The theoretical aspects of these findings were
      discussed.

PMID- 22403934
TI  - Pilot study of personality traits assessed by the Karolinska Scales of
      Personality (KSP) in asthma, atopy, and rhinitis.
AB  - Asthma and atopy are common diseases. To study associations between personality
      and asthma, atopy, rhinitis, and personality traits were measured on the
      Karolinska Scales of Personality for 193 persons working in 19 buildings with
      suspected indoor air problems. In addition, information on history of atopy,
      asthma, and rhinitis was collected by postal questionnaire. In analyses, asthma
      was associated with higher impulsiveness scores, and atopy in non-asthmatics was
      associated with higher social desirability scores and lower irritability, guilt,
      and impulsiveness scores. Non-atopic rhinitis was associated with scores on
      several anxiety-related scales, while atopic rhinitis was not associated with
      scores on the Karolinska Scales of Personality. This exploration implies that
      asthma, atopy, and rhinitis may be associated with various but different
      personality trait scores. The finding of such personality trait associations in
      persons with non-asthmatic atopy raises the question of a potential role of an
      emotional conflict in atopy and the role of personality in asthma, atopy, and
      rhinitis.

PMID- 22403935
TI  - Assessing tactile perception: effects of different visual barriers on
      performance.
AB  - Blindfolding candidates when testing their tactile performance may increase their
      anxiety. This study examined whether different visual barriers would influence
      tactile performance on timed tasks. It was hypothesised that candidates using a
      blindfold would be more anxious, but that they would benefit by the potentially
      positive effects of arousal on performance and not differ from candidates using a
      screen to limit visual access to task material. 200 participants (ages 19 to 30
      years), randomly assigned to the two conditions, completed a tactile perception
      task, as well as an anxiety scale. In contrast to the expected outcome, the
      screen sample took significantly longer to complete the task. This was
      hypothesised to be the result of increased distraction given competing cross
      modal attentional demands and the consequent visual and tactile attention
      switching. Practitioners may need to consider the influences of visual
      interference when assessing tactile performance.

PMID- 22403936
TI  - Implicit phonetic symbolism in voicing of consonants and visual lightness using
      Garner's speeded classification task.
AB  - The present study examines implicit phonetic symbolism which posits that
      arbitrary linguistic sound is related to certain aspects of characteristics of
      other modalities, such as color, touch, or emotion. In consonant discrimination
      and lightness discrimination using Garner's speeded classification paradigm,
      spoken sounds (voiced/voiceless consonants) and lightness of visual stimuli
      (black/white squares) were systematically varied to assess cross-modal
      interactions. Congruent audio-visual pairs (voiced consonants and black, and
      between voiceless consonants and white) facilitated consonant discrimination. In
      lightness discrimination, no congruent facilitation or congruence effect was
      observed. These results indicated that cross-modal interactions in implicit
      phonetic symbolism can be found in correlations between linguistic spoken sounds
      and visual lightness.

PMID- 22403937
TI  - Effect of partition board color on mood and autonomic nervous function.
AB  - The purpose of this study was to evaluate the effects of the presence or absence
      (control) of a partition board and its color (red, yellow, blue) on subjective
      mood ratings and changes in autonomic nervous system indicators induced by a
      video game task. The increase in the mean Profile of Mood States (POMS) Fatigue
      score and mean Oppressive feeling rating after the task was lowest with the blue
      partition board. Multiple-regression analysis identified oppressive feeling and
      error scores on the second half of the task as statistically significant
      contributors to Fatigue. While explanatory variables were limited to the
      physiological indices, multiple-regression analysis identified a significant
      contribution of autonomic reactivity (assessed by heart rate variability) to
      Fatigue. These results suggest that a blue partition board would reduce task
      induced subjective fatigue, in part by lowering the oppressive feeling of being
      enclosed during the task, possibly by increasing autonomic reactivity.

PMID- 22403938
TI  - Illusions of brightness, length, and now size: comparable effects derived from
      the Craik-O'Brien-Cornsweet distributions.
AB  - Analogous illusions of brightness, line length, and object size occur when
      stimulus distributions follow the Mach function. Similarly, analogous illusions
      of brightness and length are produced by stimulus distributions that follow the
      Craik-O'Brien-Cornsweet function. In Exp. 1, object size is studied using Craik
      O'Brien-Cornsweet stimuli composed of 12 clip-art representations of candles,
      swords, forks, screwdrivers, or pens. Despite their equal dimensions, the three
      objects next to the taller gradient were judged larger than the three adjacent to
      the shorter gradient. In Exp. 2, variations of the sword and screwdriver figures
      having three separations of their constituent objects were used. The illusion
      produced in Exp. 1 was replicated and, for the figures composed of screwdrivers,
      increasing separation reduced the hypothesized mis-estimations. The relationship
      of these Craik-O'Brien-Cornsweet size illusions to their brightness and length
      counterparts mirrors the relationships previously reported for Mach stimuli;
      moreover, these findings converge to suggest that the visual system registers
      size of objects with a frequency code and that illusions of size appear when
      interactions among neurons disrupt this code.

PMID- 22403939
TI  - Self-efficacy as a mediator of children's achievement motivation and in-class
      physical activity.
AB  - The present study was designed to examine the mediating effect of self-efficacy
      on relations of middle school students' four achievement goals with their
      perceptions of two motivational climates and in-class physical activity in
      physical education. The four achievement goals (mastery-approach, mastery
      avoidance, performance-approach, and performance-avoidance), perceptions of the
      motivational climate (mastery- and performance-involving climates), and self
      efficacy were measured in a sample of 194 students (93 boys, 101 girls) in a
      public school. Students' in-class physical activity was assessed using Actical
      Accelerometers. A series of multiple-regression analyses supported the mediating
      effect of self-efficacy on the relationships among students' mastery-approach
      goal, perceived mastery-involving climate, and physical activity.

PMID- 22403940
TI  - Facilitation of corticospinal excitability during motor imagery of wrist movement
      with visual or quantitative inspection of EMG activity.
AB  - The present study investigated facilitation of corticospinal excitability during
      motor imagery of wrist movement with visual or quantitative inspection of
      background electromyographic (EMG) activity. Ten healthy participants imagined
      wrist extension from a first-person perspective in response to a start cue.
      Transcranial magnetic stimulation was delivered to the motor cortex 2 sec. after
      the start cue. EMG signals were recorded from the extensor carpi radialis muscle.
      Trials with background EMG activity were discarded based on visual inspection.
      Both motor-evoked potential (MEP) and background EMG amplitudes increased during
      motor imagery. The amount of increase in MEP amplitude was positively correlated
      with the amount of increase in background EMG amplitude during motor imagery. The
      statistically significant increase in MEP amplitude during motor imagery
      disappeared when the effect of muscle activity was statistically eliminated or
      after trials with background EMG activity were discarded based on strict
      quantitative criteria. Facilitation of corticospinal excitability during motor
      imagery of wrist movement depends partially on muscle activity. Discarding
      background EMG activity during motor imagery based on visual inspection is not
      sufficient to equalize background EMG amplitude between resting and motor
      imagery. Discarding trials with background EMG activity through strict
      quantitative criteria is useful to equalize background EMG amplitude between at
      rest and during motor imagery.

PMID- 22403941
TI  - Effects of boundary height and horizontal size within boundary on perceived
      enclosure.
AB  - The permeability theory of environmental design predicts that perceived enclosure
      will be more strongly related to boundary properties such as height as opposed to
      the size of a horizontal area within a boundary. An experiment on perceived
      enclosure, provided by 24 participants on 12 spaces in a park, indicated that
      enclosure correlated at .85 with boundary height and -.60 with horizontal area.
      These results were as predicted by permeability theory.

PMID- 22403942
TI  - Physical fitness of South African primary school children, 6 to 13 years of age:
      discovery vitality health of the nation study.
AB  - Basic physical fitness was measured using 8 different measures for 10,295 South
      African children and youths (5,611 boys, 4,684 girls) ages 6 to 13 years. These
      measurements included height, weight, Body Mass Index, standing long jump,
      shuttle run, sit-and-reach, sit-up (EUROFIT testing battery), and cricket ball
      throw scores. Due to the effects of earlier apartheid laws on separating
      communities, it was hypothesized that scores for different ethnic groups may
      differ. Therefore, in addition to the calculation of basic norms and sex
      differences, ethnic differences were also tested. Height and weight, relative to
      age, were different between the various ethnic groups (Black, White, and Mixed
      ancestry) for boys, with Black boys being shorter and lighter than White boys.
      There were no differences in sit-and-reach flexibility scores between the groups.
      With the exception of the cricket ball throw for girls, White children had higher
      scores in most tests. Although not significantly different from the White
      children, in the majority of cases, the children of mixed ancestral origin had
      scores that ranged between the other two ethnic groups. These results suggest a
      need for encouraging fitness in school children, and the reintroduction of formal
      physical education into the South African school curriculum, especially into
      schools in which Black children predominate.

PMID- 22403943
TI  - Sports spectator behavior: a test of the theory of planned behavior.
AB  - The theory of planned behavior has been applied to sports and exercise behaviors.
      According to this theory, human intention to take action in a specific context is
      guided by three antecedents: attitude, subjective norm, and perceived behavioral
      control. Behavioral intention mediates the relationships between these three
      considerations and its ultimate performance. However, this theory has seldom been
      applied to the behaviors of spectators of sporting events. A sample of 269
      volleyball spectators in Taiwan was studied to examine whether people's intention
      mediated their attitudes, subjective norms, and perceived behavioral control
      toward a given behavior, watching the 2010 Federation Internationale de
      Volleyball World Grand Prix in Taipei. Regression analyses did not support
      behavioral intention as a mediator. This result is discussed in the context of
      planned behavior.

PMID- 22403944
TI  - Practice effects on decreasing and increasing force-control during periodic
      isometric movements of the index finger.
AB  - The present study examined whether improvement in control while decreasing force
      to achieve a lower force target would be facilitated by comparison of performance
      while increasing force to achieve a higher force target. Participants practiced
      control of isometric force and timing during a unimanual force production task
      cycling between 5 and 10% of maximum voluntary contraction with a target interval
      of 500 msec. Although errors and variability of both peak and valley forces and
      interval decreased during early practice, the valley force was still more
      inaccurate and variable than the peak force in the final practice. Variabilities
      of both forces did not decrease when the valley force was synchronized with an
      audible metronome pulse but did decrease when the peak force was synchronized
      with it.

PMID- 22403945
TI  - [Analysis of the efficacy of low-frequency pulse therapy in the combination with
      radon baths for the treatment of patients with different variants of the clinical
      course of cervical dorsopathy].
AB  - The authors present the results of analysis of combined physiobalneotherapy in
      the patients with neurological manifestations of degenerative lesions in the
      cervical spine with special reference to the clinical form of the disease. The
      use of unified criteria for the assessment of cervico-brachial pain syndrome and
      clinico-neuropsychological status of the patients in conjunction with auxiliary
      research techniques made it possible to demonstrate the high efficacy of the
      treatment using low-frequency pulse therapy supplemented by the application of
      radon baths. The best therapeutic effect was achieved in a group of patients
      presenting with cervico-brachial syndrome treated during the periods of
      exacerbation of cervical spine osteochondrosis. A less pronounced positive effect
      was documented in the group having the recurrent clinical course of cervico
      brachial pain syndrome due to degenerative and dystrophic lesions in the cervical
      spine and diskopathy. The difference between the responses of the two groups of
      patients can be accounted for not only by the severity of degenerative lesions in
      the cervical spine but also by the changes in their psychoemotional sphere.

PMID- 22403946
TI  - [Electrical pulse therapy for the treatment of the patients with obliterative
      atherosclerosis of the vessels in the lower extremities].
AB  - The authors report the results of the application of electrical pulses to the
      region of lumbar ganglia for the treatment of patients with obliterative
      atherosclerosis of the blood vessels in the lower extremities. It was shown that
      the temporary blockade of sympathetic regulation of the lower limb arteries
      promotes reduction of vascular tone in the distal segments of the lower
      extremities, stimulates collateral blood flow, and improves microcirculation in
      ischemic tissues(specifically, following reconstructive surgery on the lower limb
      arteries).

PMID- 22403947
TI  - [Changes of hemodynamics during the treatment of patients with neurologic pain
      syndromes by the method of dynamic electrical neurostimulation].
AB  - The Doppler ultrasound technique was used to study blood flow characteristics for
      the evaluation of the efficacy of the treatment of painful neurological syndromes
      with the help of a DiaDENS apparatus allowing for dynamic changes of
      electrostimulation parameters. A significant improvement of the extracranial
      cerebral blood flow was achieved as early as the mid-course of 10 treatment
      sessions when the most pronounced stabilization of the clinical characteristics
      was apparent. Marked heterogeneity of responses of extracranial vessels to the
      therapeutic effect of dynamic electrostimulation (DENS) was documented, possibly
      due to the redistribution of the blood flow in certain vascular areas during the
      treatment. DENS applied to the lumbar region was shown to induce positive
      dynamics of the initially impaired blood flow in the tibial artery. It is
      concluded that positive hemodynamic changes in the cerebral blood flow constitute
      an important component of the anesthetic and general sanogenetic actions of DENS.

PMID- 22403948
TI  - [Oxygen-transporting function of the blood following general air cryogenic
      therapy].
AB  - The present clinical and laboratory study of the effects of general air cryogenic
      therapy on the characteristics of blood supply included practically healthy
      subjects. The study has demonstrate that dosed cold stress promotes adaptive
      capacities of the organism by modulating the oxygen-transporting function of the
      blood that in its turn stimulates the adaptive mechanisms and leads to decoupling
      tissue respiration. It is concluded that general air cryogenic therapy can be
      recommended as an instrument for the improvement of endurance of and
      resistibility to the action of hypoxemia in special groups of people under the
      low temperature conditions.

PMID- 22403949
TI  - [The application of electrical stimulation by bipolar pulsed currents and
      galanthamine electrophoresis for the rehabilitation of patients with diabetes
      mellitus].
AB  - Clinical observations provided evidence of the positive effects of multichannel
      electrical stimulation by bipolar pulsed currents in combination with
      galanthamine electrophoresis applied for the treatment of patients with
      complicated diabetes mellitus. Such treatment facilitated normalization of water
      and carbohydrate metabolism and reduction of the body weight; moreover, it
      improved blood circulation and the state of the nervous system.

PMID- 22403950
TI  - [The application of sinusoidal modulated currents for the treatment of biliary
      sludge in an outpatient clinic].
AB  - The objective of the present study was to evaluate therapeutic effects of
      sinusoidal modulated currents (SMC) applied for the treatment of patients at
      different stages of biliary sludge (BS) under conditions of an outpatient clinic.
      Biliary sludge is currently considered to be a precursor of cholelithiasis known
      to be a leading pathology of the digestive system responsible for the high
      surgery rate. It was shown that the introduction of the technique based on
      sinusoidal modulated currents into the clinical practice of an outpatient clinic
      increases the efficacy of management of the patients presenting with stage 1 and
      2 biliary sludge and showing neither well-apparent clinical symptoms nor signs of
      metabolic disorders that imply the necessity of more thorough examination and
      combined application of sinusoidal modulated currents and mediacmental therapy.

PMID- 22403951
TI  - [The application of sinusoidal modulated current electrophoresis of a
      phytopreparation for the rehabilitation of patients with knee joint
      osteoarthrosis].
AB  - The objective of the present comparative study was to estimate the efficacy of
      the rehabilitative treatment of the patients presenting with knee joint
      osteoarthrosis using sinusoidal modulated current electrophoresis of a
      phytopreparation. It was shown that the combination of phyto- and
      electrotherapies allows to more efficaciously alleviate pain in the knee joint
      and improve its function than pharmacotherapy or its combination with amplipulse
      therapy. The proposed approach produces no adverse effects. Its ultimate effect
      is a marked improvement of the patients' quality of life.

PMID- 22403952
TI  - [Non-medicamental correction of the hormonal and psycho-autonomic status in women
      with pathology of the reproductive system treated at health resort of the
      Krasnodar Krai (region)].
AB  - The authors report the results of the study on the hormonal and psychovegetative
      status, functional activity of the vegetative nervous system, the level of
      activity of the protective and adaptive hemostatic mechanisms, and the clinical
      features of concomitant extragenital pathology in 90 adolescent girls suffering
      uterine bleeding. All the patients had gone through in-patient and out-patient
      phases of therapy, sixty of them were selected for the spa and resort
      rehabilitative treatment. The use of rehabilitative technologies on an individual
      basis at a spa and resort facility made it possible to ensure rather high
      efficacy of the combined therapeutic and preventive treatment of reproductive
      system pathology and concomitant psycho-vegetative disorders. It helped to
      decrease the frequency of relapses of uterine bleeding and exacerbation of the
      accompanying extragenital diseases.

PMID- 22403953
TI  - [Peculiarities of metabolic rearrangement of gas-transporting function of the
      blood in the pregnant women under the influence of medical ozone applied in
      obstetrical practice].
AB  - This clinical and laboratory study was designed to evaluate the influence of an
      ozone-oxygen mixture on the characteristics of blood oxygen supply in pregnant
      women presenting with chronic placental insufficiency. The study has demonstrate
      that dosed ozone application modulates the oxygen-transporting function of the
      blood and promotes adaptive capacities of the organism by activation of aerobic
      metabolism and stabilization of cellular membranes. It is concluded that the
      proposed method can be recommended for the treatment of women with the
      complicated course of pregnancy in order to improve their endurance of and
      resistibility to the action of hypoxemia.

PMID- 22403954
TI  - [The application of combined physical therapy for the treatment of women with
      pelvic pain syndrome].
AB  - A total of 98 women presenting with pelvic pain syndrome of different etiology
      (inflammatory diseases of small pelvic organs following surgical interventions,
      dysmenorrhoea, ovulatory syndrome) were enrolled in this study with an object of
      estimating the efficacy of the combined central and local application of
      physiotherapeutic techniques. An AVIM-1 apparatus was used to cause vibration in
      and apply a magnetic field to the perineal region. Transcranial magnetotherapy
      and electrostimulation were applied centrally using an AMO-ATOS-E device. The
      study has demonstrated that the combined central and local application of
      physiotherapeutic techniques supplemented by medicamental treatment according to
      the indications made it possible to attenuate pain syndrome by 64.6% and improve
      the vegetative nervous function and cerebral blood circulation by 30% and 18%
      respectively compared with the women in the control group. Moreover, the 1.5-2
      fold improvement of the main characteristics of microcirculation was achieved.
      The overall resistance increased under the influence of physiotherapy in 71% of
      the women which promoted their reproductive potential and enhanced the
      probability of pregnancy.

PMID- 22403955
TI  - [Estimation of the functional reserves of the organism and identification of the
      subjects at risk of common diseases].
AB  - The existing system of preventive medical examination of the population engaged
      in economic activities with the purpose of early diagnostics of a variety of
      disorders and pathological conditions practically does not use the technologies
      for the assessment of health reserves and identification of the groups at risk of
      developing common diseases and premorbid conditions. We examined a total of 67
      subjects (32 men and 35 women) and treated the data obtained by using the
      mathematical methods of statistics. The results were used to develop the "Health
      Reserves" hardware and software complex whose diagnostic potential and
      informational content permit to identify individuals at high risk of developing
      common diseases, quantitatively evaluate functional reserves of the human
      organism, and predict the efficacy of application of non-medicamental
      technologies for their enhancement.

PMID- 22403956
TI  - [The role of mud-forming microflora in the generation of biological activity of
      therapeutic peloids from Siberia].
AB  - The authors report the results of comprehensive evaluation of medicinal salt
      saturated silt sulfide peloids from the bottom deposits of several lakes in the
      Novosibirsk and Altai regions. These peloids are extensively used for therapeutic
      and recreational purposes and appear to have good prospects for even a wider
      application in the future. The role of autochthonous microflora in the formation
      of peloid biological activities and antimicrobial properties has been elucidated.
      Information about the sanitary, microbiological and environmental situation in
      the areas of peloid deposits is presented.. The therapeutic efficacy of the
      sulfide peloids extracted from Lake Ostrovnoye, Novosibisk region, is discussed.

PMID- 22403957
TI  - [The present-day organization of spa and resort services for the population of
      the Russian Federation (Part 1)].
AB  - The main principles underlying the present-day organization of spa and resort
      services for the population of the Russian Federation are described. The emphasis
      is laid on the procedures for the selection and referral to spa and resort
      facilities of the patients, both adults and children, in need of
      balneotherapeutic treatment. The relevant normative and legal regulations are
      discussed.

PMID- 22403958
TI  - [The development of mass physical culture and sports in the constituent entities
      of the Russian Federation as a factor of formation of the healthy life style].
AB  - Provision of proper conditions for the creation of healthy life style is a
      priority of the state policy in this country with special attention given to the
      development of the mass physical culture and sports. The present paper contains
      information on the proportion of the population of the Russian Federation
      regularly engaged in physical culture and sports, provision of necessary sport
      facilities, and budgetary expenditures for the purpose in different constituent
      entities of the country. Public satisfaction with the conditions available for
      mass physical education and sports is discussed. Taking into account the low
      average life expectancy of the country's population and the increasing morbidity
      and traumaticity rates among the younger generation, it appears impossible to
      address the global challenge of improving the health of the nation without
      promotion of mass physical culture and sports and renewal of interest in these
      activities among the general population.

PMID- 22403959
TI  - [Thalassotherapy for the patients suffering osteoarthrosis. The medical
      technology].

PMID- 22403960
TI  - The AANA Journal Special Research Edition: two views on its relevance.
AB  - Research is the active pursuit of discovering new and relevant information
      through systematic inquiry. A foundational role of the AANA Journal is bringing
      research to our readers that assists us in refining the way we think about and
      practice our specialty. The age of evidence-based practice is upon us, and we
      must actively embrace the opportunity that it provides to merge research, skill,
      intuition, and humanitarianism.

PMID- 22403961
TI  - Environmental and financial impact of a hospital recycling program.
AB  - Recycling decreases greenhouse gases (GHGs) emitted from waste disposal. A recent
      study determined the environmental and financial impact of recycling at a 148-bed
      acute care hospital in Cincinnati, Ohio. The hospital added single-stream
      recycling to its nonhazardous waste disposal practices in September 2008. The
      study measured the amount of nonhazardous waste generated and disposal costs from
      September 2008 to March 2009 for comparison with the same 6-month period in 2007
      2008, calculating the environmental benefit using the Environmental Protection
      Agency's Waste Reduction Model (WARM). This study revealed that recycling
      benefits the environment and saves money. Recycling reduced GHG emissions by 34
      metric ton carbon equivalents (MTCEs) and saved 632 million BTUs of energy.
      Pearson correlation for waste generation (r = 0.99, P = .002) demonstrates that
      the amount of waste generated between the control and intervention periods were
      very similar. Pearson correlation for facility operations as measured by
      admissions, outpatient visits, emergency room visits, and number of employees (r
      = 0.99, P < .007) also showed the 2 time periods to be very similar. The
      hospital's cost to dispose of nonhazardous waste decreased more than $4,670 after
      single-stream recycling.

PMID- 22403962
TI  - Knowledge of palliative and end-of-life care by student registered nurse
      anesthetists.
AB  - As part of a 5-year study funded by the National Cancer Institute, all graduate
      nursing students, including student registered nurse anesthetists (SRNAs)
      participated in a 2-credit-hour course called Interdisciplinary Palliative Care.
      Medical and health science students also participated in the course, with more
      than 800 students completing the course to date. The sample consisted of 62
      master's-level students enrolled in either the first or second year of the nurse
      anesthesia program. A pretest-posttest design was used to determine changes in
      palliative care knowledge and perceived effectiveness in palliative care skills.
      There was an overall improvement in knowledge and attitudes related to course
      content. Students reported that, through the development of new knowledge, they
      felt better able to care for and advocate for their patients. Further research is
      needed into the appropriate roles that Certified Registered Nurse Anesthetists
      (CRNAs) can play in palliative and end-of-life care.

PMID- 22403963
TI  - Perioperative music and its effects on anxiety, hemodynamics, and pain in women
      undergoing mastectomy.
AB  - There is increasing interest in evaluating the use of nonpharmacologic
      interventions such as music to minimize potential adverse effects of anxiety
      reducing medications. This study used a quasi-experimental design to evaluate the
      effects of a perioperative music intervention (provided continuously throughout
      the preoperative, intraoperative, and postoperative periods) on changes in mean
      arterial pressure (MAP), heart rate, anxiety, and pain in women with a diagnosis
      of breast cancer undergoing mastectomy. A total of 30 women were assigned
      randomly to a control group or to the music intervention group. Findings
      indicated that women in the intervention group had a greater decrease in MAP and
      anxiety with less pain from the preoperative period to the time of discharge from
      the recovery room compared with women in the control group. Music is a
      noninvasive and low-cost intervention that can be easily implemented in the
      perioperative setting, and these findings suggest that perioperative music can
      reduce MAP, anxiety, and pain among women undergoing mastectomy for breast
      cancer.

PMID- 22403964
TI  - Investigation of the anti-inflammatory, antinociceptive effect of ellagic acid as
      measured by digital paw pressure via the Randall-Selitto meter in male Sprague
      Dawley rats.
AB  - Ellagic acid (EA), a dietary supplement, is purported to have anti-inflammatory,
      antinociceptive properties via cyclooxygenase (COX) inhibition. We measured the
      antinociceptive efficacy of EA alone and in combination with a nonselective COX
      inhibitor and a selective COX-2 inhibitor. We assigned 54 male Sprague-Dawley
      rats to 1 of 6 groups to be given the following compounds: (1) vehicle, (2)
      ketorolac (nonselective COX inhibitor), (3) meloxicam (selective COX-2
      inhibitor), (4) EA, (5) EA plus ketorolac, and (6) EA plus meloxicam.
      Inflammatory pain was induced in the right hind paw by injecting carrageenan.
      Rats were given study compounds via intraperitoneal injection 30 minutes after
      paw injections. Pain tolerance was assessed using the Randall-Selitto instrument
      at 30 minutes and 4, 8, 12, and 24 hours. The highest pressure tolerated was
      recorded in grams. The analysis of variance suggested a significant difference (F
      = 2.44; P = .048). The least significant difference post hoc analysis suggested
      that at 8 hours, EA plus ketorolac provided greater antinociception than all
      other compounds (P = .04). Furthermore the combination of EA plus ketorolac
      provided longer antinociception than all other compounds (P = .03) such that EA
      plus ketorolac was effective at 24 hours.

PMID- 22403965
TI  - Clinical education experiences: perceptions of student registered nurse
      anesthetists.
AB  - The purpose of this study was to describe the experiences and attitudes of
      student registered nurse anesthetists (SRNAs) related to clinical instruction.
      This descriptive study used a cross-sectional survey method with a regionally
      stratified randomly selected sample of SRNA members from the American Association
      of Nurse Anesthetists data bank. A total of 2,673 SRNAs were invited by email to
      respond to an online, 54-item questionnaire; 696 SRNAs participated. Verbal abuse
      was reported by almost 70% of SRNA participants, but fewer experienced sexual
      harassment (13%), physical abuse (14%), or racial discrimination (72%). However,
      SRNAs reported that their Certified Registered Nurse Anesthetist (CRNA)
      preceptors most often served as positive role models. These SRNAs found CRNA
      preceptors, unique cases, reading, and clinical lectures more helpful to their
      clinical learning compared with grand rounds, surgeons, and anesthesiology
      residents. The SRNAs' perceptions of the ideal behavioral characteristics for
      CRNA preceptors included calmness during stressful events, use of nonthreatening
      communication, clear communication, and encouraging independent decision making.
      The educational process for nurse anesthetists is continually evolving and
      improving. Study findings offer insights that may assist in improvements in the
      clinical component of SRNA education.

PMID- 22403966
TI  - Perioperative administration of gabapentin for shoulder arthroscopy: a
      prospective, randomized, double-blind, placebo-controlled study.
AB  - Recent studies suggest gabapentin has opioid-sparing effects and may reduce acute
      postoperative pain. However, there is limited research on the efficacy of
      gabapentin when combined in a multimodal approach after shoulder arthroscopy
      under general anesthesia with an interscalene block. We conducted prospective,
      double-blind study of 70 patients who were randomized to receive either 300 mg of
      gabapentin or placebo 1 hour before surgery, then twice a day for 2 days. The
      primary outcome was average pain scores. Secondary outcomes included differences
      in morphine equivalents, adverse effects, and sleep patterns. No significant
      differences in pain scores were found on day 1 (gabapentin mean [SD], 4.23
      [2.61], vs placebo, 4.61 [2.57]; P = .58) or day 2 (gabapentin, 4.26 [2.39], vs
      placebo, 4.03 [2.34]; P = .71). Total morphine equivalents on day 1 (gabapentin,
      9.75 mg [6.58 mg], vs placebo, 9.52 mg [4.75 mg]; P = .88) and day 2 (gabapentin,
      9.21 mg [6.66 mg], vs placebo, 6.93 mg [5.44 mg]; P = .17) were similar. Adverse
      effects and sleep patterns were similar (P > .05). These results suggest this
      dosing regimen of gabapentin is not efficacious in improving outcomes in patients
      undergoing shoulder arthroscopy under general anesthesia with an interscalene
      block.

PMID- 22403967
TI  - Workplace aggression: assessment of prevalence in the field of nurse anesthesia.
AB  - The purpose of this study was to assess the prevalence of workplace aggression in
      the field of nurse anesthesia. A second focus was to assess the negative impact
      of aggressive behavior and how it affects the work environment of Certified
      Registered Nurse Anesthetists (CRNAs). Data analyses from the Workplace
      Aggression Research Questionnaire revealed that CRNAs experience verbal, active,
      and direct aggression more frequently than physical, passive, and indirect
      aggression. For all types of aggression, CRNAs indicated that supervisors are the
      most likely perpetrators, followed by coworkers. Female CRNAs experience
      aggression in the workplace more often than did male CRNAs, with the largest
      percentage of incidents occurring against CRNAs 21 to 39 years old. A significant
      positive correlation exists between the level of workplace stress and experiences
      of verbal, direct, and active aggression. Qualitative data were consistent with
      the quantitative data, and converging patterns of verbal, active, and direct
      aggression emerged as the aggressive behaviors reported most frequently by CRNAs.
      Two additional key themes, patient safety and oppression, also emerged from the
      data.

PMID- 22403968
TI  - A comparison of the pain perceived during intravenous catheter insertion after
      injection with various local anesthetics.
AB  - This study compared 4 local anesthetics, 1% lidocaine, 1% lidocaine with sodium
      bicarbonate, 2% chloroprocaine, and 0.5% bupivacaine, in a double-blinded manner
      for pain on intradermal injection and pain during subsequent intravenous (IV)
      cannulation with an 18-gauge catheter. The subjects rated their pain, using 100
      mm visual analog scales, related to the local injection itself and again after
      the IV catheter was inserted. No statistical differences were noted in pain
      scores after the injection of the local anesthetic (P = . 134) or on insertion of
      the IV catheter itself (P = .394). However, there was a low correlation between
      the pain perceived during the injection of local anesthetic and insertion of the
      IV catheter (r = 0.483; P = .001). We found that there were no differences in
      pain produced by 1% lidocaine, 1% lidocaine with sodium bicarbonate, 2%
      chloroprocaine, and 0.5% bupivacaine during intradermal injection. There were
      also no differences in pain produced by an 18-gauge IV catheter being inserted
      after administration of any of these local anesthetics. Thus, any of these 4
      local anesthetics may be used, and the choice may be based on other factors such
      as price and convenience.

PMID- 22403969
TI  - Congruence of perceived effective clinical teaching characteristics between
      students and preceptors of nurse anesthesia programs.
AB  - This study continues landmark research, by Katz in 1984 and Hartland and Londoner
      in 1997, on characteristics of effective teaching by nurse anesthesia clinical
      instructors. Based on the literature review, there is a highlighted gap in
      research evaluating current teaching characteristics of clinical nurse anesthesia
      instructors that are valuable and effective from an instructor's and student's
      point of view. This study used a descriptive, quantitative research approach to
      assess (1) the importance of 24 characteristics (22 effective clinical teaching
      characteristics identified by Katz, and 2 items added for this study) of student
      registered nurse anesthetists (SRNAs) and clinical preceptors, who are Certified
      Registered Nurse Anesthetists, and (2) the congruence between the student and
      preceptor perceptions. A Likert-scale survey was used to assess the importance of
      each characteristic. The study was conducted at a large Midwestern hospital. The
      findings of this study did not support the results found by Hartland and Londoner
      based on the Friedman 2-way analysis. The rankings of the 24 characteristics by
      the students and the clinical preceptors in the current research were not
      significantly congruent based on the Kendall coefficient analysis. The results
      can help clinical preceptors increase their teaching effectiveness and generate
      effective learning environments for SRNAs.

PMID- 22403970
TI  - Prophylactic isopropyl alcohol inhalation and intravenous ondansetron versus
      ondansetron alone in the prevention of postoperative nausea and vomiting in high
      risk patients.
AB  - Patients identified as high risk for postoperative nausea and vomiting (PONV) are
      often treated prophylactically with intravenous (IV) ondansetron and an
      additional agent. Limited options exist for a second agent with no adverse
      effects. The purpose of this investigation was to determine if combining the
      prophylactic inhalation of isopropyl alcohol (IPA) vapors, an agent with no
      adverse effects, with IV ondansetron would be more effective than IV ondansetron
      alone in the prevention of PONV in high-risk patients. A total of 76 patients at
      high risk for PONV were randomized into control (n = 38) and experimental (n =
      38) groups. All patients received IV ondansetron before emergence from general
      anesthesia. In addition, the experimental group inhaled IPA vapors before
      induction. Severity of PONV was measured using a 0 to 10 verbal numeric rating
      scale. Other measured variables included time to onset and incidence of PONV, 24
      hour composite nausea score, and satisfaction with nausea control. No significant
      differences in demographics, surgical or anesthesia time, number of risk factors,
      severity or incidence of PONV, or satisfaction scores were noted. Prophylactic
      inhalation of IPA vapors in combination with IV ondansetron was no more
      efficacious than IV ondansetron alone in the prevention of PONV in a high-risk
      population.

PMID- 22403971
TI  - Evaluation of the anxiolytic properties of tetrahydropalmatine, a Corydalis
      yanhusuo compound, in the male Sprague-Dawley rat.
AB  - The purpose of this study was to investigate the anxiolytic effects of
      tetrahydropalmatine (THP) and its potential interaction with the benzodiazepine
      binding site on the gamma-aminobutyric acid (GABAA) receptor in the male Sprague
      Dawley rat. Tetrahydropalmatine (THP), an active component isolated from the
      Chinese herbal plant Corydalis yanhusuo, is used in Asia for its analgesic,
      sedative, and hypnotic properties during herbal therapy. Fifty-five rats were
      assigned to 1 of 5 groups with 11 rats per group: 1) control (vehicle), 2) THP,
      3) midazolam, 4) midazolam with THP, and 5) flumazenil with THP. In this study,
      the elevated plus-maze measured the behavioral components of anxiety and motor
      movements. The data were analyzed using a 2-tailed multivariate analysis of
      variance to determine if a significant difference existed followed by the least
      significant difference post hoc test. The findings suggest that THP, 25 mg/kg,
      given via intraperitoneal injection, results in significant anxiolysis and
      decreased motor movements. Furthermore, flumazenil, 3 mg/kg, does not fully
      antagonize the effects of THP.

PMID- 22403972
TI  - The antibacterial and antiplaque effectiveness of mouthwashes containing
      cetylpyridinium chloride with and without alcohol in improving gingival health.
AB  - This article briefly discusses the antibacterial action ofcetylpyridinium
      chloride (CPC) and its efficacy in the removal of bacterial plaque as an adjunct
      to the mechanical cleaning of tooth surfaces. It reviews new studies on the
      effectiveness of mouthwash formulations containing CPC against two common oral
      bacteria species and in disrupting plaque biofilms. Finally, this article reviews
      three clinical studies which support that the daily use of mouthwashes containing
      0.075% CPC, with and without alcohol, represents a valuable complement to daily
      mechanical plaque control.

PMID- 22403973
TI  - In vitro antibacterial efficacy of cetylpyridinium chloride-containing
      mouthwashes.
AB  - OBJECTIVE: The objective of this study was to examine the ability of three CPC
      containing mouthwashes to kill planktonic bacteria in an in vitro short-exposure
      assay. METHODS: This blind study was conducted on two common oral bacterial
      species: Aggregatibacter (Actinobacillus) actinomycetemcomitans and Streptococcus
      mutans. The following mouthwashes were tested: two containing 0.075% CPC and
      0.05% NaF in an alcohol-free base, and one containing 0.075% CPC and 0.05% NaF
      plus 6% alcohol. Additionally, a 0.05% NaF-only mouthwash was included as a
      negative control. Bacteria were exposed to one of the test mouthwashes for 30
      seconds and then washed thoroughly, serially diluted, and plated on appropriate
      media to determine viable bacterial counts. Viable counts were converted to a log
      reduction in colony forming units (CFUs) relative to the negative control.
      RESULTS: All three test mouthwashes included in this study gave a statistically
      significant reduction of > 3 log CFUs relative to samples treated with the
      negative control. CONCLUSION: All three experimental 0.075% CPC mouthwash
      formulas gave a > 99.9% reduction in viable bacteria of both species following 30
      seconds of treatment.

PMID- 22403974
TI  - Efficacy of an alcohol-free CPC-containing mouthwash against oral multispecies
      biofilms.
AB  - OBJECTIVE: The aim of this work was to develop two static-model multispecies oral
      biofilm systems to compare the efficacy of a placebo mouthwash to an alcohol-free
      mouthwash containing 0.075% CPC. METHODS: Two model biofilm systems were used: a
      24-well glass-bottom microplate (GM) system and a chamber slide (CS) system.
      These were inoculated with Schaedler media containing pooled, unfiltered saliva.
      During incubation at 37 degrees C in 5% CO2, Schaedler media was replaced every
      24 hours. Five-day and 10-day multispecies biofilms in the GM and CS systems were
      then exposed to phosphate buffered saline, the placebo mouthwash, or the alcohol
      free 0.075% CPC-containing mouthwash. Biofilms were visualized in three
      dimensions by Confocal Laser Scanning Microscopy (CLSM), and fluorometric
      analyses were performed on biofilms in the GM system. RESULTS: CLSM demonstrated
      that regardless of the model system used, the alcohol-free 0.075% CPC-containing
      mouthwash solution increased the number of damaged biofilm cells. The efficacy of
      CPC was inversely related to the age of the biofilm. A contrariety between the
      two biofilm systems was that the CS system indicated that alcohol-free 0.075% CPC
      containing mouthwash partially disrupted biofilms. Fluorometric analysis ofGM
      biofilms also demonstrated that the alcohol-free 0.075% CPC-containing mouthwash
      damaged biofilm cells. CONCLUSION: Two static oral multispecies model biofilms
      systems demonstrated that an alcohol-free 0.075% CPC-containing mouthwash had
      greater antimicrobial efficacy than a placebo mouthwash. The alcohol-free 0.075%
      CPC-containing formulation is effective against multispecies oral biofilms.

PMID- 22403975
TI  - A clinical study to assess the 12-hour antimicrobial effects of cetylpyridinium
      chloride mouthwashes on supragingival plaque bacteria.
AB  - OBJECTIVE: This randomized double-blind clinical study evaluated the
      antimicrobial efficacy of two mouthwashes containing (1) 0.075% cetylpyridinium
      chloride (CPC) + 0.05% sodium fluoride (NaF) in an alcohol-free base and (2)
      0.075% CPC + 0.05% NaF in a 6% alcohol base, versus a negative control mouthwash
      containing 0.05% NaF in an alcohol-free base on numbers of bacteria in
      supragingival plaque 12 hours after a single use and 12 hours after 14 days' use.
      METHODS: Enrolled subjects completed a one-week washout phase prior to providing
      baseline samples of supragingival plaque that were analyzed for numbers of
      anaerobic microorganisms. Subjects were randomized to a treatment group and
      instructed to rinse with 20 mL of the assigned mouthwash for 30 seconds. Post
      treatment microbiological analyses were conducted on plaque samples collected 12
      hours after the first use of each assigned mouthwash and after completing 14 days
      of twice-daily use of each assigned mouthwash. Oral examinations were completed
      by a dentist at each sample collection to assess soft and hard tissue oral health
      over the course of the study. RESULTS: The study enrolled 188 adults (mean age
      45.78 years; age range 23-69). Subjects rinsing with the CPC-containing mouthwash
      realized a statistically significant (p < 0.05) reduction in numbers of
      supragingival anaerobic bacteria at the 12-hour evaluation after a single use. In
      comparison to the control mouthwash, use of the CPC mouthwash in an alcohol base
      resulted in a 35.3% reduction in numbers of anaerobic plaque bacteria, while the
      CPC mouthwash in an alcohol-free base demonstrated a 34.5% reduction. Further,
      the analysis after twice-daily use for 14 days indicated that the CPC mouthwash
      in an alcohol base demonstrated a 73.8% reduction in anaerobic plaque bacteria,
      while the CPC mouthwash in an alcohol-free base demonstrated a 70.9% reduction in
      anaerobic plaque bacteria versus the control mouthwash. CONCLUSION: The CPC
      mouthwash in an alcohol-free base reduced supragingival plaque bacteria by 34.5%
      and 70.9% compared to the control mouthwash 12 hours after a single use and after
      14 days of use, respectively. In addition, the CPC mouthwash in an alcohol base
      reduced supragingival bacteria by 35.3% and 73.8% compared to the control
      mouthwash 12 hours after a single use and after 14 days of use, respectively.
      There were no statistically significant differences between the CPC-containing
      mouthwashes at either of the post-treatment time points.

PMID- 22403976
TI  - Evaluation of the antiplaque efficacy of two cetylpyridinium chloride-containing
      mouthwashes.
AB  - OBJECTIVE: The purpose of this clinical study was to evaluate the efficacy in
      reducing dental plaque regrowth of two mouthwashes containing 0.075%
      cetylpyridinium chloride (CPC), one with 6% alcohol and one alcohol-free, as
      compared to a negative control mouthwash without CPC, using the Modified Gingival
      Margin Plaque Index (MGMPI). METHODS: The study was a double-blind, randomized,
      three-way crossover, controlled design. Following a washout period, subjects
      reported to the dental clinic where they were instructed to brush their teeth,
      used their assigned mouthwash, and were scored by the examining dentist for
      plaque using the MGMPI method. Subjects were instructed to refrain from all oral
      hygiene for the next 24 hours, except for rinsing with their assigned mouthwash
      12 hours post-brushing. After this 24-hour period, subjects returned to the
      dental clinic and were once again scored for plaque. This sequence of washout
      followed by mouthwash use and plaque scoring was repeated until each subject had
      used all three mouthwashes. An ANOVA was conducted to assess between-group
      differences. RESULTS: The two test mouthwashes significantly reduced plaque
      regrowth over a 24-hour period (p < 0.05) as compared to the negative control
      mouthwash. The difference between the CPC-containing mouthwashes was not
      significant (p = 0.4868). CONCLUSION: Two mouthwashes containing 0.075% CPC, one
      with 6% alcohol and the other alcohol-free, were found to be safe and effective
      in reducing plaque accumulation when compared a negative control mouthwash
      without CPC. In short-term studies, the MGMPI appears useful for evaluating the
      antiplaque efficacy of mouthwash products.

PMID- 22403977
TI  - A comparative investigation to evaluate the clinical efficacy of an alcohol-free
      CPC-containing mouthwash as compared to a control mouthwash in controlling dental
      plaque and gingivitis: a six-month clinical study on adults in San Jose, Costa
      Rica.
AB  - OBJECTIVE: This study was designed to evaluate the clinical efficacy of an
      antiplaque alcohol-free mouthwash containing 0.075% cetylpyridinium chloride
      (CPC) and 0.05% sodium fluoride (NaF), as compared to a control mouthwash
      containing only 0.05% NaF, in controlling established dental plaque and
      gingivitis after three and six months of product use. METHODS: This was a single
      center, parallel-group, two-cell, double-blind, randomized clinical study.
      Prospective adult male and female subjects from San Jose, Costa Rica reported to
      the clinical facility having refrained from all oral hygiene procedures for 12
      hours, and from eating, drinking, or smoking for four hours prior to their visit.
      Qualifying subjects who presented with Gingival Index scores (Loe and Silness
      Index) of at least 1.0 and Plaque Index scores (Turesky Modified Quigley-Hein
      Index) of at least 1.5 were allowed to participate in this study. Subjects were
      randomly assigned to one of two treatment groups according to their baseline
      gingival and plaque scores. In the first treatment group (Test), subjects used an
      alcohol-free mouthwash containing 0.075% CPC and 0.05% NaF, whereas in the second
      treatment group (Control), subjects used a mouthwash containing only 0.05% NaF.
      Gingivitis and plaque assessments, and examinations of oral hard and soft tissues
      were conducted after three months and six months of product use. RESULTS: One
      hundred and ten (110) subjects complied with the protocol and completed the six
      month study. After six months of product use, the Test Mouthwash group exhibited
      statistically significant reductions from baseline with respect to Gingival
      (33.5%), Gingival Interproximal (34.5%), Gingival Severity (63.2%), Plaque
      (33.6%), Plaque Interproximal (30.0%), and Plaque Severity (73.6%) Index scores.
      After six months of product use, the Control Mouthwash group exhibited
      statistically significant increases from baseline with respect to Gingival
      (6.9%), Plaque Interproximal (7.2%), and Plaque Severity (32.7%) Index scores.
      Furthermore, after six months of product use, the Control Mouthwash group
      exhibited reductions from baseline with respect to Plaque (6.1%), Gingival
      Interproximal (3.6%), and Gingival Severity (1.1%) Index scores which were not
      statistically significant. After three months of product use, the Test Mouthwash
      group exhibited statistically significant reductions in Gingival (25.0%),
      Gingival Interproximal (22.3%), Gingival Severity (38.9%), Plaque (26.1%), Plaque
      Interproximal (22.4%), and Plaque Severity (75.0%) Index scores as compared to
      the Control Mouthwash group. After six months of product use, the Test Mouthwash
      group exhibited statistically significant reductions in Gingival (38.1%),
      Gingival Interproximal (37.1%), Gingival Severity (63.6%), Plaque (36.5%), Plaque
      Interproximal (33.2%), and Plaque Severity (78.5%) Index scores as compared to
      the Control Mouthwash group. CONCLUSION: The results of this double-blind
      clinical study support that 1) an alcohol-free mouthwash containing a combination
      of 0.075% CPC and 0.05% NaF produces statistically significant reductions in
      dental plaque and gingivitis after three and six months compared to baseline, and
      2) the alcohol-free CPC mouthwash provides a statistically significantly greater
      level of efficacy in controlling established dental plaque and gingivitis after
      three and six months of product use as compared to the Control Mouthwash
      containing only NaF.

PMID- 22403978
TI  - Remineralization of early caries by a nano-hydroxyapatite dentifrice.
AB  - OBJECTIVE: The purpose of this randomized, double-blind, crossover, in situ study
      was to evaluate the efficacy of nano-hydroxyapatite (nHAP) dentifrices on caries
      remineralization and demineralization inhibition. METHODS: Three demineralized
      enamel blocks (A,B,C) and one healthy block (D), cut from each of 30 molars, were
      exposed respectively to dentifrices of A) 5% nHAP, B) 10% nHAP, C) 1100 ppm
      fluoride, and D) 10% nHAP via an intra-oral appliance worn by 30 adults in this
      four-phase study lasting 28 days per phase. Baseline and post-test mineral loss
      (delta Z) and lesion depth (LD) were quantified using microradiography. RESULTS:
      Pair-wise comparison (baseline versus test) demonstrated significant (p < 0.001)
      reductions in delta Z and LD in A, B, and C. ANOVA showed no significant
      differences among the three products in percent mineral gain. No demineralization
      occurred in the sound enamel specimens exposed intra-orally while using 10% nHAP.
      CONCLUSION: nHAP dentifrice caused remineralization comparable to a fluoride
      dentifrice, and inhibited caries development, thus suggesting that an nHAP
      dentifrice can be an effective alternative to fluoride toothpaste.

PMID- 22403979
TI  - Clinical comparison of plaque inhibition effects of a novel stabilized stannous
      fluoride dentifrice and a chlorhexidine digluconate dentifrice using digital
      plaque imaging.
AB  - OBJECTIVE: To compare the plaque inhibition efficacy of a novel 0.454% stannous
      fluoride (SnF2) test dentifrice with sodium hexametaphosphate and stannous
      chloride to a chlorhexidine digluconate (0.05%), aluminium lactate (0.8%), and
      aluminium fluoride marketed control dentifrice (Lacalut Aktiv or AlF3/Chx).
      METHODS: This was a randomized, two-treatment, two-period, double-blind crossover
      study that compared the SnF2 test dentifrice to the AlF3/Chx control dentifrice.
      Each of the two treatment periods lasted for 17 consecutive days of product use,
      during which subjects were required to brush twice per day with their assigned
      dentifrice using a standard manual toothbrush (Oral-B P35 Indicator). The two
      periods of the crossover were separated by a four-day washout period. Plaque
      levels on the facial anterior tooth surfaces were evaluated and averaged among
      three assessment days at the end of each treatment period using digital plaque
      imaging analysis (DPIA). The evening prior to assessments, subjects only brushed
      lingual surfaces. Assessment time points were carried out in the morning
      following no morning brushing (A.M. pre-brush), following 40 seconds of brushing
      with the assigned dentifrice (A.M. post-brush), and in the afternoon (P.M.). The
      DPIA captured images were used to calculate and analyze visible plaque coverage.
      RESULTS: Twenty-eight subjects were randomized and completed the study. At each
      assessment time point, the SnF2 test dentifrice demonstrated a statistically
      significant lower plaque level compared to the AlF3/Chx dentifrice: A.M. mean pre
      brush 15.9% lower, p < 0.05; A.M. mean post-brush 22.2% lower, p < 0.05; P.M.
      mean 24.3% lower, p < 0.005. CONCLUSION: Compared to the AlF3/Chx control
      dentifrice, the novel SnF2 test dentifrice significantly inhibited plaque
      regrowth overnight and during the day. Immediately after brushing there was also
      significantly less plaque coverage with the SnF2 test dentifrice.

PMID- 22403980
TI  - Subgingival delivery of oral debriding agents: a proof of concept.
AB  - OBJECTIVE: This study is a proof of concept to determine the efficacy of a custom
      fabricated tray in placing antimicrobial and debriding agents in the periodontal
      pockets of persons with active gingival infections. Localized subgingival
      delivery of antimicrobial and antibiotic agents is routinely employed as
      adjunctive therapy for the treatment and management ofperiopathogens associated
      with periodontal disease. Because these delivery techniques often face time
      constraints and impose temporary restrictions on patient brushing and flossing, a
      custom-formed prescription dental tray can be used to deliver and maintain
      medications in periodontal pockets between office visits and without brushing or
      flossing restrictions. The ability of this tray to maintain sufficient
      concentrations of medication in the periodontal pockets to have a therapeutic
      effect is evaluated here with theoretical modeling and practical application.
      METHODS: Hydrogen peroxide is an oral debriding agent and oral wound cleanser
      with antimicrobial properties. The debriding effect of 1.7% hydrogen peroxide gel
      was tested in vitro on Streptococcus mutans biofilm using glass carriers for
      collection. Diffusion modeling tested the potential of the customized tray to
      place hydrogen peroxide gel into the sulcus in the presence of crevicular fluid
      flow. Changes in periodontal microflora with scanning electron microscopy
      analysis of in vivo paper point site sampling were analyzed before and after a
      thin ribbon of 1.7% hydrogen peroxide gel (approximately 0.7 gm) and a
      subtherapeutic dose (three drops) of Vibramycin (50 mg/5 ml) were placed via
      Perio Trays into periodontal pockets, ranging from 4-8 mm at daily prescribed
      intervals for two to five weeks. RESULTS: In vitro results indicate that 1.7%
      hydrogen peroxide gel breaks down the exopolysaccharide slime and cell walls ofS.
      mutans, and begins to debride the cells from glass carriers within 10 minutes.
      Diffusion modeling indicates that hydrogen peroxide can penetrate into the deeper
      pockets (9 mm), but also its concentration in these deep pockets will increase
      over wearing time in the absence of degradation by peroxidases and catalase. Site
      sampling data confirm diffusion modeling results, with evidence that medication
      delivered with the prescription tray reduced subgingival bacterial loads and
      enhanced healing of corresponding oral tissues. CONCLUSION: The prescription
      Perio Tray effectively placed medication in the gingival sulcus. Mathematical
      modeling indicated Perio Tray placement of hydrogen peroxide gel in periodontal
      pockets with depths up to 9 mm over 15 minutes treatment time was theoretically
      possible. Pathology reports reveal reductions in subgingival bacterial loads and
      improvements in pretreatment pocket depths of up to 8 mm after 1.7% hydrogen
      peroxide and Vibramycin Syrup were prescribed for use with the Perio Tray. The in
      vitro analysis indicating that hydrogen peroxide is the active and effective oral
      debriding agent needs to be confirmed with additional studies.

PMID- 22403981
TI  - Safety of an intra-oral hearing device utilizing a split-mouth research design.
AB  - OBJECTIVE: The auditory deficits of Single Sided Deafness (SSD) can be treated
      effectively with a novel device, SoundBite, that delivers sound by applying
      imperceptible vibratory signals to the teeth (hereafter referred to as an intra
      oral hearing device). The intra-oral hearing device is placed around two
      maxillary teeth and is similar to a small partial denture or retainer. The goal
      of this study was to report how this removable hearing device affects the oral
      structures. METHODS: Twenty-two SSD patients wearing an intra-oral hearing device
      were enrolled in a prospective study for six months. Differences (delta) between
      the device-anchoring teeth and the equivalent contralateral non-device teeth were
      evaluated with four dental parameters using a paired t-test. Hearing thresholds
      were evaluated as a function of alveolar bone support using linear regression.
      RESULTS: Compared to the non-device teeth, the hearing device teeth did not
      exhibit any increased recession (delta = 0.1 mm, p-value = 0.48), increased
      pocket depth (delta = 0.0 mm, p-value = 0.48), increased root resorption (delta =
      4%, p-value = 0.43), or increased alveolar bone loss (delta = 0.0 %, p-value =
      0.43). There was no association between the amount of alveolar support and
      hearing thresholds (delta = 0.2, p-value = 0.34). CONCLUSION: The intra-oral
      component of the hearing device did not adversely affect the dental structures of
      the subjects in this trial.

PMID- 22403983
TI  - Enhancement of plaque removal by baking soda toothpastes from less accessible
      areas in the dentition.
AB  - OBJECTIVE: To determine if baking soda toothpastes are relatively more effective
      than non-baking soda toothpastes in promoting plaque removal from less accessible
      sites in the dentition. METHODS: Several single-brushing comparisons of baking
      soda and non-baking soda toothpastes for their overall ability to remove plaque
      have been published. In this study, individual comparisons of these published
      data, comparing the plaque removal performance of baking soda and non-baking soda
      toothpastes at various sites in the dentition, were examined to see if there were
      any site-dependant performance trends. The site-specific single-brushing data
      were then combined and analyzed in two ways. Meta-analyses of the clinical
      studies were performed to compare baking soda's relative plaque removal advantage
      at various sites in the mouth using paired t-testing at p <0.05. Also, plaque
      index reductions at various sites due to brushing with baking soda toothpastes
      were graphically compared with plaque index reductions due to brushing with non
      baking soda dentifrices. The percent relative plaque removal advantage for baking
      soda toothpastes at various sites were plotted against the reduction in plaque
      index due to brushing with non-baking soda toothpastes. RESULTS: Individual
      comparisons showed that brushing with the toothpastes containing baking soda
      generally removed significantly more plaque from each site than brushing with
      toothpastes without baking soda. The relative efficacy advantage for baking soda
      toothpastes was consistently higher at sites where the non-baking soda
      toothpastes removed less plaque. Meta-analytical comparisons confirmed baking
      soda toothpastes to be relatively more effective in enhancing plaque removal from
      sites where less plaque was removed compared to brushing with non-baking soda
      toothpastes (p < 0.05). Graphically, the baking soda toothpastes' relative plaque
      removal advantage could be seen to increase hyperbolically with decreasing plaque
      removal by the non-baking soda toothpastes with which they were compared. We
      presuppose that the reason less plaque is removed by non-baking soda toothpastes
      at some sites than others is that these sites are less accessible to the
      toothbrush. CONCLUSION: These results show that baking soda toothpastes are
      relatively more effective in enhancing plaque removal from harder-to-reach areas
      of the dentition (p <0.05), i.e., from lingual than facial surfaces, from
      posterior than anterior areas, and from proximal than mid-surface sites.

PMID- 22403982
TI  - The biofilm-controlling functions of rechargeable antimicrobial N-halamine dental
      unit waterline tubing.
AB  - OBJECTIVE: A study was conducted to test the biofilm-controlling functions of N
      halamine tubing over an eight-month period. METHODS: A laboratory system,
      simulating a teaching dental clinic, was used to test rechargeable N-halamine
      tubing (T) compared to an untreated control (C) using the unit manufacturer's
      tubing. For the long-term study, a recharged tubing (RC) treated with bleach was
      used to compare with the test (T) and the control (C) tubing. Source tap water
      was cycled through the lines at 1.4 mL/minute, five minutes on and 25 minutes
      off, eight hours/day, five days/week. Every three weeks, samples of effluent,
      recovered adherent bacteria from inside tubing surfaces, and SEM images were
      examined for bacterial and biofilm growth. After sampling, a recharging solution
      of chlorine bleach (1 : 10 dilution) was run through T and RC lines, left
      overnight, and rinsed out the next morning. One-way ANOVAs and Spearman
      correlations were performed to detect significant differences for T, RC, and C,
      and determine significance with time period and source water, respectively.
      RESULTS: Mean log CFU/mL for C effluent > T (p = 0.028), and C tubing > T (p =
      0.035). Spearman correlations were significant between effluent and source water
      level for T (rho = 0.817), and T tubing (0.750); between RC tubing and source
      water level (rho = 0.836), and time (rho = 0.745); and between C and time (rho =
      0.873). SEM imaging confirmed the presence of biofilm inside RC and C, but not
      inside T. CONCLUSION: N-halamine tubing completely inhibited biofilm formation
      without negatively affecting the physical properties of the effluent water.
      Further research on N-halamine tubing using a pure water source is recommended,
      as T effluent bacterial levels reflected the source tap water quality and
      proliferation of planktonic bacteria with no biofilm activity.

PMID- 22403984
TI  - Clinical evidence for the superior efficacy of a dentifrice containing 8.0%
      arginine and calcium carbonate in providing instant and lasting relief of dentin
      hypersensitivity.
AB  - This paper briefly discusses recent scientific and clinical research validating
      the effectiveness of a toothpaste containing 8.0% arginine and calcium carbonate,
      known as Pro-Argin technology, including clinical evidence for the superior
      efficacy of this toothpaste versus a potassium-based desensitizing toothpaste. It
      also introduces new clinical data which prove that a toothpaste containing 8.0%
      arginine and calcium carbonate delivers superior instant and lasting relief of
      dentin hypersensitivity compared to a toothpaste containing 8% strontium acetate.

PMID- 22403985
TI  - Advances in the clinical management of dentin hypersensitivity: a review of
      recent evidence for the efficacy of dentifrices in providing instant and lasting
      relief.
AB  - This paper summarizes the current state of knowledge of the epidemiology,
      etiology, and clinical management of dentin hypersensitivity, with special
      emphasis on the evidence for the effectiveness of commonly available sensitivity
      relief toothpastes. It reviews the scientific and clinical research validating
      the effectiveness of a recently introduced toothpaste containing 8.0% arginine
      and calcium carbonate, known as Pro-Argin technology, including clinical evidence
      for the superior efficacy of this toothpaste versus potassium-based sensitivity
      relief toothpastes. It critiques recently published studies on a strontium-based
      sensitivity relief toothpaste. Finally, it summarizes new clinical data from
      three parallel, randomized, head-to-head studies comparing the efficacy of a
      toothpaste containing 8.0% arginine and calcium carbonate (positive control) to a
      strontium-based sensitivity relief toothpaste (test) in delivering superior
      instant and lasting sensitivity relief. The results of these new clinical studies
      clearly support the conclusions that 1) a toothpaste containing 8.0% arginine and
      calcium carbonate provides superior efficacy with respect to both immediate and
      lasting relief of dentin hypersensitivity compared to a toothpaste containing 8%
      strontium acetate, and 2) a toothpaste containing 8% strontium acetate is no more
      effective in providing immediate relief of dentin hypersensitivity than a regular
      fluoride toothpaste.

PMID- 22403986
TI  - Comparison of the effects on dentin permeability of two commercially available
      sensitivity relief dentifrices.
AB  - OBJECTIVE: The in vitro effects of two commercial sensitivity relief dentifrices,
      one containing 8.0% arginine, calcium carbonate, and 1450 ppm fluoride as sodium
      monofluorophosphate (MFP), and the other containing 8% strontium acetate and 1040
      ppm fluoride as sodium fluoride, in occluding dentin tubules and reducing dentin
      fluid flow were compared in a blinded study using hydraulic conductance (Flodec).
      METHODS: Human dentin segments were cut from extracted molars, mounted on acrylic
      blocks, etched, and connected to a Flodec to measure hydraulic conductance.
      Segments were divided into two groups (n = 6) and treated for one minute with
      either the arginine/calcium carbonate dentifrice or the strontium acetate
      dentifrice. The blocks were rinsed, connected to the Flodec, and the conductance
      was measured. Blocks were rinsed again and incubated in phosphate-buffered saline
      (PBS) for at least two hours before the next treatment. The cycle was repeated
      for a total of three treatments (one using a fingertip and the next two using a
      toothbrush). After the third treatment, the blocks were incubated in PBS
      overnight and conductance was re-measured. The two groups were further divided
      into three sets of two segments each, which were challenged for one minute with
      either 6% citric acid, orange juice, or grapefruit juice. RESULTS: The hydraulic
      conductance study showed that the dentifrice containing 8.0% arginine, calcium
      carbonate, and 1450 ppm fluoride provided a significantly higher percentage
      reduction in fluid flow immediately after fingertip application, as well as after
      two brushing cycles, compared to the dentifrice containing 8% strontium acetate
      and 1040 ppm fluoride. After various acid challenges, the percentage reduction in
      fluid flow of dentin treated with the arginine/calcium carbonate dentifrice
      remained significantly higher than that of the strontium acetate dentifrice.
      These results are highly consistent with the results from an independent clinical
      study which showed that the arginine/calcium carbonate dentifrice provided dentin
      hypersensitivity relief immediately after direct topical application with a
      fingertip and massage for one minute per sensitive tooth, whereas the strontium
      acetate dentifrice did not. CONCLUSION: Based on this in vitro hydraulic
      conductance study, the dentifrice containing 8.0% arginine, calcium carbonate,
      and 1450 ppm fluoride was significantly more effective in reducing fluid flow
      through dentin tubules as a result of occlusion than the dentifrice containing 8%
      strontium acetate and 1040 ppm fluoride. Further, the superior occlusion obtained
      with the arginine/calcium carbonate dentifrice was resistant to acid challenge.

PMID- 22403987
TI  - Comparison of clinical efficacy of three toothpastes in reducing dentin
      hypersensitivity.
AB  - OBJECTIVE: The objective of the study was to compare the clinical efficacy in
      reducing dentin hypersensitivity of a test toothpaste containing 8% strontium
      acetate and 1040 ppm fluoride as sodium fluoride (NaF) in a silica base, to a
      positive control toothpaste containing 8.0% arginine and 1450 ppm fluoride as
      sodium monofluorophosphate (MFP) in a calcium carbonate base, and a negative
      control toothpaste containing 1100 ppm fluoride as NaF in a silica base. METHODS:
      Subjects identified with two hypersensitive teeth using the tactile (Yeaple
      Probe) and air blast (Schiff's Scale) hypersensitivity methods were assigned to
      their treatment group. There were 50 subjects per group. Subjects then self
      applied the assigned toothpaste to their hypersensitive teeth using a fingertip,
      then brushed their teeth at home using the same toothpaste twice daily for seven
      days. Dentin hypersensitivity and oral tissues were evaluated at baseline,
      immediately after the single application, and after seven days. A chi-square
      analysis was conducted to examine the effects with respect to gender between
      treatments. Comparisons of the age and baseline hypersensitivity data among
      groups were performed using the analysis of variance (ANOVA). Within-treatment
      effects were analyzed using the paired t-test, while the analysis of covariance
      (ANCOVA) was used to determine the between-treatment effects. The post hoc
      Tukey's test was performed for the pair-wise comparisons using a significance
      level of alpha = 0.05. RESULTS: All 150 subjects complied with the protocol and
      completed the study. The positive control toothpaste containing 8.0% arginine and
      1450 ppm fluoride as MFP in a calcium carbonate base provided statistically
      significant improvements in mean tactile and air blast dentin hypersensitivity
      scores compared to the negative control toothpaste containing 1100 ppm fluoride
      as NaF in a silica base (p < 0.05). The toothpaste containing 8.0% arginine and
      1450 ppm fluoride as MFP in a calcium carbonate base (positive control) also
      provided statistically significant improvements in mean tactile and air blast
      dentin hypersensitivity scores compared to the test toothpaste containing 8%
      strontium acetate and 1040 ppm fluoride as NaF in a silica base. The test
      toothpaste and the negative control toothpaste were not significantly different
      from each other. CONCLUSION: The test toothpaste containing 8% strontium acetate
      and 1040 ppm fluoride as NaF in a silica base, when used for a single topical
      application and twice-daily brushing for seven days, does not provide
      statistically significant relief of dentin hypersensitivity compared to a
      negative control toothpaste containing 1100 ppm fluoride as NaF in a silica base.
      In contrast, the positive control toothpaste containing 8.0% arginine and 1450
      ppm fluoride as MFP in a calcium carbonate base provided significantly reduced
      dentin hypersensitivity compared to the negative control toothpaste, and was
      significantly more effective than the test toothpaste containing 8% strontium
      acetate and 1040 ppm fluoride as NaF in a silica base.

PMID- 22403988
TI  - Comparative evaluation of the efficacy of three commercially available
      toothpastes on dentin hypersensitivity reduction: an eight-week clinical study.
AB  - OBJECTIVE: The objective of this eight-week, single-center, three-cell, double
      blind, and randomized clinical study was to evaluate the dentin hypersensitivity
      reduction efficacy of three commercially available toothpastes: 1) Colgate
      Sensitive Pro-Relief Toothpaste (also marketed as elmex Sensitive Professional);
      2) Sensodyne Rapid Relief Toothpaste; and (3) Crest Cavity Protection Toothpaste.
      METHODS: 150 subjects, having two teeth with tactile and air blast
      hypersensitivity, were assigned to one of the three study groups (50/group).
      Subjects were then asked to brush their teeth for one minute, twice daily, with
      the given toothpaste. The dentin hypersensitivity and oral tissues were evaluated
      at baseline, two weeks, four weeks, and eight weeks. Comparison of the treatment
      groups with respect to gender was conducted using a chi-square analysis, and with
      respect to age and baseline hypersensitivity scores was performed using the
      analysis of variance (ANOVA). Within-treatment effects were analyzed using the
      paired t-test, while the analysis of covariance (ANCOVA) was used to examine
      between-treatment effects. The post hoc Tukey test was performed for pair-wise
      comparisons. All statistical tests were two-sided using a significance level of
      alpha = 0.05. RESULTS: After two, four, and eight weeks of daily use of the
      products, all three groups showed a statistically significant reduction from
      baseline in tactile and air blast dentin hypersensitivity (p < 0.05). Colgate
      Sensitive Pro-Relief toothpaste produced a significant improvement in mean
      tactile and air blast dentin hypersensitivity scores, and was more effective than
      Sensodyne Rapid Relief toothpaste and Crest Cavity Protection toothpastes (p <
      0.05). CONCLUSION: Colgate Sensitive Pro-ReliefToothpaste, used twice daily,
      significantly reduces dentin hypersensitivity, and is significantly more
      effective in reducing dentin hypersensitivity than Sensodyne Rapid Relief
      Toothpaste and Crest Cavity Protection Toothpaste.

PMID- 22403989
TI  - Clinical efficacy in reducing dentin hypersensitivity of a dentifrice containing
      8.0% arginine, calcium carbonate, and 1450 ppm fluoride compared to a dentifrice
      containing 8% strontium acetate and 1040 ppm fluoride under consumer usage
      conditions before and after switch-over.
AB  - OBJECTIVE: The objective of this 16-week, double-blind, randomized, switch-over
      design study was to compare the efficacy in reducing dentin hypersensitivity of a
      dentifrice containing 8.0% arginine, calcium carbonate, and 1450 ppm fluoride as
      sodium monofluorophosphate (Colgate Sensitive Pro-Relief [also marketed as elmex
      Sensitive Professional]) to a desensitizing dentifrice containing 8% strontium
      acetate and 1040 ppm fluoride as sodium fluoride (Sensodyne Rapid Relief) under
      relevant consumer usage conditions. METHODS: Qualifying subjects from the San
      Francisco, CA, USA area, who presented two hypersensitive teeth with a tactile
      hypersensitivity score (Yeaple Probe) between 10 and 50 grams of force and an air
      blast hypersensitivity score of 2 or 3 (Schiff Cold Air Sensitivity Scale),
      participated in this two-phase double-blind study. Subjects were randomly
      assigned to one of two test groups. The first phase of the study consisted of
      twice-daily at-home brushing with the first assigned dentifrice for eight weeks.
      The second phase of the study consisted of switching product use to the second
      assigned dentifrice for a second eight-week period. Dentin hypersensitivity
      examinations, which comprised tactile and air blast hypersensitivity measures, as
      well as examinations of oral hard and soft tissues, were conducted at baseline,
      at the completion of the first study phase, and at two weeks and eight weeks of
      the second phase. RESULTS: One-hundred and twenty-one subjects complied with the
      study protocol and completed the study. Study Phase I: Subjects who brushed twice
      daily for eight weeks with the arginine/calcium carbonate dentifrice experienced
      statistically significant improvements in mean tactile and air blast
      hypersensitivity scores (51.3% and 39.4%, respectively) relative to that
      experienced by subjects who brushed with the strontium acetate dentifrice. Study
      Phase II: Subjects who brushed with the arginine/calcium carbonate dentifrice for
      the first eight weeks of the study and then switched to brush with the strontium
      acetate dentifrice for the second eight weeks of the study, did not exhibit
      further improvements in mean tactile or mean air blast hypersensitivity scores
      after two and eight weeks of switch-over product use. However, subjects who
      brushed with the strontium acetate dentifrice for the first eight weeks of the
      study and then switched to brush with the arginine/calcium carbonate dentifrice
      exhibited statistically significant improvements in mean tactile and air blast
      hypersensitivity scores two weeks (35.2% and 29.9%, respectively) and eight weeks
      (40.3% and 35.3%, respectively) after product switch-over. Relative to the
      subjects who switched from twice-daily brushing with the arginine/calcium
      carbonate dentifrice to brush with the strontium acetate dentifrice, those who
      switched from brushing with the strontium acetate dentifrice to brush with the
      arginine/calcium carbonate dentifrice exhibited statistically significant
      improvements in mean tactile hypersensitivity scores (10.3%) and in mean air
      blast hypersensitivity scores (16.3%) eight weeks after product switch-over.
      CONCLUSION: Eight weeks of brushing with Colgate Sensitive Pro-Relief(elmex
      Sensitive Professional) provides significant reductions in mean dentin
      hypersensitivity relative to the identical use of Sensodyne Rapid Relief.
      Additionally, the dentin hypersensitivity reductions achieved by twice-daily
      brushing with Sensodyne Rapid Relief are significantly improved by switching to
      twice-daily brushing with Colgate Sensitive Pro-Relief (elmex Sensitive
      Professional) for two and eight weeks. Further, the dentin hypersensitivity
      reductions achieved by twice-daily brushing with Colgate Sensitive Pro-Relief
      (elmex Sensitive Professional) are not improved by switching to twice-daily
      brushing with Sensodyne Rapid Relief for two or eight weeks. Eight weeks' use of
      Colgate Sensitive Pro-Relief (elmex Sensitive Professional), after having used
      Sensodyne Rapid Relief for an initial eight-week time period, provides
      statistically significant improvements in dentin hypersensitivity relative to
      eight weeks' use of the Sensodyne Rapid Relief.

PMID- 22403991
TI  - [Effect of misclassification of the place of residence on incidence estimates:
      the example of child cancer in a local health authority in Rome, Italy].
AB  - A study on cancer of the lymphatic and hematopoietic tissue among residents aged
      0-14 years was conducted by the Local Health Unit RMD (Rome, Italy; period 2003
      09; codes of the International Classification of Diseases, Ninth Revision,
      Clinical Modification: 200-208). Age and gender Standardized Mortality and
      Hospitalization Ratios were computed in order to compare observed and expected
      cases, using municipal rates as reference. Place of residence at the time of
      admission, as recorded in the Hospital Registry, was compared with the
      information recorded in the Municipal Registers and the correlation between the
      two sources was calculated by Cohen's Kappa. No mortality nor morbidity excesses
      were observed in the study area. Although 14% of children were not confirmed as
      being resident at the time of admission, the Cohen's Kappa indicates a strong
      correlation between the Municipal Registry and the Hospital Registry (84%). The
      analyses restricted to children with ascertained residence did not yield
      different results. For those whose residence was not confirmed, the mismatch of
      information between the Municipality Registry and the Hospital Registry needs to
      be clarified.

PMID- 22403992
TI  - [Acute hospital care for the elderly in Italy: comparison between 2001 and 2006].
AB  - The continous health expenditure increase in developed countries is often related
      with the acute hospital care of the elderly. To monitor the characteristics of
      elderly acute hospital care included the expenditure trend is crucial in order to
      identify the appropriateness of this care. The aim of this study is to describe
      quality and quantity of in-hospital care use of elderly population in Italy in
      2006 and to compare the results with the same information gathered for 1996 and
      2001. All the 2006 acute hospital admission longer than one day of the patients
      older than 64 years sourced from the Register of Discharge Form of the Italian
      Ministry of Health have been analyzed. A list of the 30 more frequent diagnoses
      has been compiled and compared with the same list compiled for 2001. On the basis
      of the National Fee for each Disease Related Group an analysis of the hospital
      expenditure has been carried out. The correlation between DRGs National Fees and
      frequency of the diagnosis in the discharge form has been based on the 80
      diagnosis that has been recorded for more than 10.000 discharge forms in 2006. A
      relevant increase of acute hospital admission for respiratory, cardiovascular and
      urinary pathologies among the elderly has been observed. Moreover the number of
      hospital admissions for major joints and implant of lower limbs is doubled from
      1996. The total health expenditure for the elderly acute care longer than one day
      is increased of 6.3% and a positive correlation between higher DRGs fees and
      higher frequency of diagnosis has been observed (Pearson correlation value =
      0.478; p<0.001 - cubic regression R-square value = 0.301; p<0.001). The hospital
      acute care use of the elderly patients seems to be more related to emergency care
      than in the past, while a decrease of DRGs related to chronic diseases and
      generic diagnosis has been observed. The more frequent cause of in-hospital
      admission seems to be related also to a higher DRGs fee. As already observed in
      the past years, a trend towards the use of more expensive DRGs could be detected.

PMID- 22403990
TI  - [Global health education in Italian medical schools: survey from 2007 to 2010].
AB  - Global Health (GH) issues are becoming a common feature of Medical and Public
      Health Schools worldwide. In Italy the Network for Education on Global Health
      (RIISG) was created with the purpose of spreading the concept of GH. The aim of
      the study was to assess the availability of educational opportunities in Italian
      Health Faculties from 2007 to 2010. A survey was carried out using a
      questionnaire administered to Professors. A frequency distribution of GH elective
      courses, grouped by three Italian geographical areas (North, Centre, South and
      Islands), for each academic year was assessed. The features of the courses -
      consistent with the pattern of course, suggested by RIISG - were analysed through
      a score. From 2007 onwards, in chronological order the surveyed faculties were
      40, 36, 36 and the main coverage of survey was 92%. The courses listed were 26,
      22 and 40 respectively for each academic year considered. The average of the
      courses number highlighted an increasing trend: national mean rose from 0.65 (SD
      +/- 1.53) in 2007 to 1.11 (SD +/- 1.18) in 2010. Regarding the evaluation of
      consistency a national improvement was shown. The assessment revealed a limited
      educational offer and differences between macroareas. Further investigations are
      needed.

PMID- 22403993
TI  - [The INHES cohort study on the health status of nurses in Italy: research
      protocol].
AB  - Due to the intense emotional involvement and the often problematic working
      conditions characterizing their profession, Nurses appear to be especially
      susceptible to the negative effects of a complex set of stressors, with important
      repercussions to their health. Nevertheless, scientific literature assessing the
      health status of Nurses in Italy is still scarce. With INHES (Italian Nurses'
      HEalth Study), we propose to remedy this gap by implementing a cohort study which
      will start from the analysis of some local healthcare facilities and which may
      subsequently extend throughout the country. Study participants will be Nurses
      selected according to the following inclusion criteria: 1) age between 30 and 55
      years; 2) having been employed in the current healthfacilityfor the last five
      years; 3) having performed care duties in wards or in day care services for the
      last five years. The objectives of this study, which will be carried out through
      the administration of a validated questionnaire, are the following: to measure
      the incidence and prevalence rates of a series of diseases in the nursing
      population, highlighting potential correlations with working activity, job
      related stress or environmental and personal risk factors; to assess the quality
      of life and psychological health of the participants, evaluating the interference
      of psychophysical disorders with their work and social activities; to investigate
      the implementation of wellness promotion, prevention, case management and
      disability management policies by healthcare facilities. The evidence gathered
      will provide a valid scientific support for the development of more effective
      policies for protecting Nurses' health, with positive social and economic
      repercussions for the entire community.

PMID- 22403994
TI  - [State of health of the population residing in the town of Barengo and in
      surrounding communities, site of a field used as landfill for MSW: analysis of
      the general incidence and causes from 2003 to 2009].
AB  - The research provides an observational epidemiological study to detect whether
      there is a cluster or a local excess morbidity rate in Barengo, site of a solid
      waste quarry, as well as to define the initial hypothesis of causal relationships
      and then trigger if necessary, more stringent and specific inferential
      assessments. The population studied consists of all the residents in the eight
      municipalities that make up the area next to the dump site with Barengo as the
      central point, site of the plant; the reference population in Barengo,
      Cavaglietto, Momo, Cavaglio, Briona, Vaprio, Fara and Sizzano add up to about
      11,122 residents. The overall mortality data for the years 2000-2009 show
      excesses for cardiovascular diseases, digestive system as well as nervous and
      respiratory systems for both sexes; to monitor next would be the frequency of
      some cancers such as, bone, kidney, small intestine and ovary. Given the current
      epidemiological considerations, today we cannot derive the determining conditions
      of health levels observed. The viability of a health risk identification can be
      achieved only in a second intervention capable of inferring random links in
      regards to the presence of specific risk situations.

PMID- 22403995
TI  - [Methodological aspects of clinical and economic impact of vaccine interventions
      and HTA. Focus on HPV vaccination].
AB  - The aim of the present study is to analyze the methodological and technical
      aspects of Health Technology Assessment (HTA) as a tool for the clinical and
      economic impact of vaccine interventions, describe and comment the main studies
      at the national level, with a particular focus on HPV vaccination. The work was
      conducted in 3 phases: a) revision of the scientific literature, strictly linked
      to methodologies adopted in different studies on economic evaluations on HPV
      vaccines and analysis of Guidelines for building models for the economic
      assessment; b) analysis of the peculiarities and critical elements of economic
      evaluations in the field of vaccinology, from the clinical and epidemiological
      point of view, as well as the recognition of lack of knowledge on HPV infection
      dynamics; c) a comparative analysis of the two italian studies and of the results
      coming from them. Many differences between studies were found. Nevertheless,
      there is a general agreement on the economic profile of HPV vaccination for
      adolescent girls, if compared with the actual practice on the prevention of
      cervical carcinoma (pap-test screening). All the models showed a significant
      impact in terms of reduction of the incidence of cervical carcinoma and related
      mortality, in the long run, as well as a reduction of pre-cancer lesions and
      abnormal Pap tests. HTA approach has been recently recognized as a tool for
      decision making in vaccinology, and its methodologies and procedures are
      currently debated by public health experts. There is a strong need to continue
      the work in improving the model techniques of economic evaluations concerning HPV
      vaccination, as well as the adoption of homogeneous methods and standards, with
      the aim of helping the decision process in the field of Public Health.

PMID- 22403996
TI  - [Nature-like swimming ponds and bathing: public health issues for congruous
      guidelines].
AB  - Nature-like swimming ponds represent an emerging approach to recreational waters.
      The substitution of traditional disinfection with biodepuration enhances
      environmental sustainability, but implies relevant public health issues. No
      European regulations are available while several countries delivered local
      guidelines. Appropriate microbiological analysis, user education, and correct
      water management based on HACCP approach, represent key points for the
      development of future guidelines.

PMID- 22403997
TI  - [Segmentation of retinal blood vessels based on centerline extraction].
AB  - The precise estimation of blood vessel centerline and width is a prerequisite
      condition for the quantitative and visualized diagnosis of blood vessel disease
      in fundus images. In this paper, a retinal blood vessel segmentation algorithm
      based on centerline extraction is proposed. According to the characteristics of
      the fundus image and retinal blood vessels, the image is convoluted with the
      masks of discrete Gaussian partial derivative kernels. The centerline is
      determined by differential geometric properties of the blood vessels and the
      width is also calculated. The precision of our method can reach sub-pixel level
      with a fast computation speed. The experiments on several kinds of fundus images
      showed that the method worked quickly and accurately.

PMID- 22403998
TI  - [A preliminary clinical validation of a brain deformation corrective system based
      the linear elastic model].
AB  - In order to increase the accuracy of image guided neurosurgery (IGNS), we
      developed a brain deformation corrective system (BDCS) based on linear elastic
      model. To investigate the fidelity of such a system, two cases of cerebral tumor
      resection were conducted in our paper. According to our experiments, the average
      shift error after craniotomy was reduced to (1.00 +/- 0.63)mm from (4. 97 +/- 3.
      53)mm and the average prediction rate was (72.27 +/- 20.37)%. The results showed
      that the system was convenient and fast to operate and presented a promising
      pathway to compensating for brain deformation during neurosurgery.

PMID- 22403999
TI  - [Low-dose CT perfusion imaging based on pre-scan regulation and on reconstruction
      with sparsity constraints].
AB  - The long-period CT perfusion imaging leads to an excess amount of radiation dose
      to the patient. However, the radiation dose could be significantly reduced if a
      previous normal-dose image is acquired before a set of low-dose scans of
      perfusion, and a filtering processing is performed on the differences between the
      current low-dose images and the previous normal-dose image, then the results are
      added to the previous image. But the selection of plenty of parameters makes the
      algorithm complicated. This paper proposes an innovative approach performed in
      sinogram domain instead of in image domain. First a normal-dose image and a set
      of low-dose projection data are acquired before the perfusion. Second the
      perfusion information is commendably reconstructed with sparsity constraints of
      the differences between current low-dose perfusion sinograms and previous low
      dose sinogram. Finally, the reconstructed perfusion information is added to the
      previous normal-dose image. The proposed method was validated by simulated
      experiments with a set of brain CT perfusion images, which showed that the new
      method provided more accurate perfusion information; the time-attenuation curve
      was more close to that for normal-dose scan and the mean transit time more
      repeatable.

PMID- 22404000
TI  - [Gait analysis of adults' slips and falls based on COM equilibrium recovery
      response].
AB  - Aiming at slips and falls occurred during adults' walking, a method was proposed
      that could predict slips and falls based on center of mass (COM) recovery
      response. This method, based on the Kane's equation dynamic walking model of the
      lower extremities, can be used to rapidly detect dynamic parameters in each gait
      cycle, and analyze any instantaneous balance status of slips and falls, and the
      characteristic COM curves may be accomplished on the basis of the measurement
      data. Moreover, causations, phases and processes about gaits of adults' slips and
      falls could be judged and analyzed by the characteristic curves. When the
      distance between the projection point of COM to base of support (BOS) domain is
      more than 0.012-0. 015m, human gaits have a tendency to slip and fall. When COM
      velocity response curve value is between 0.9-2. 1m/s, human gaits are normal and
      stable. The experimental results of slips and falls about the two different age
      groups showed that the method is able to predict and revise slips and falls by
      the COM recovery response characteristic curves.

PMID- 22404001
TI  - [Research and implementation of the TLS network transport security technology
      based on DICOM standard].
AB  - With the development of medical information, Picture Archiving and Communications
      System (PACS), Hospital Information System/Radiology Information System(HIS/RIS)
      and other medical information management system become popular and developed, and
      interoperability between these systems becomes more frequent. So, these enclosed
      systems will be open and regionalized by means of network, and this is
      inevitable. If the trend becomes true, the security of information transmission
      may be the first problem to be solved. Based on the need for network security, we
      investigated the Digital Imaging and Communications in Medicine (DICOM) Standard
      and Transport Layer Security (TLS) Protocol, and implemented the TLS transmission
      of the DICOM medical information with OpenSSL toolkit and DCMTK toolkit.

PMID- 22404002
TI  - [Suppression of spiral waves and spatiotemporal chaos in cardiac tissue by
      elevating potassium ion concentration].
AB  - The suppression of spiral waves and spatiotemporal chaos in cardiac tissue was
      studied based on cardiac model. We proposed two strategies of suppressing spiral
      wave and spatiotemporal chaos. One was to elevate the extracellular potassium ion
      concentration suddenly. This method can effectively suppress spiral waves and
      spatiotemporal chaos when the elevated extracellular potassium ion concentration
      reaches a critical value, especially when the spiral wave pinned to defects also
      can be suppressed. The other was to let the extracellular potassium ion
      concentration varies periodically while the amplitude of concentration was
      limited. We found that the method could effectively suppress spiral waves and
      spatiotemporal chaos when the related parameters were properly chosen. But it can
      not suppress the pinned spiral waves. And the control mechanism is discussed in
      this paper.

PMID- 22404003
TI  - [MDCT features and anatomic-pathological basis of the diseases in central
      thoracic-abdominal junctional region].
AB  - This paper is to determine relationship between MDCT features and anatomic
      pathology of the diseases in central thoracic-abdominal junctional region. 3
      cadavers were cut transversely and another 3 vertically to observe the anatomy of
      thoracic-abdominal junctional zone. 93 patients with diseases in central thoracic
      abdominal junctional zone were scanned with MDCT. The correlation between MDCT
      features of the diseases in central thoracic-abdominal junctional region and the
      anatomic-pathology of the diseases in this region was evaluated. On cadaver
      sections, central thoracic-abdominal junctional region was an area between
      anterior chest wall and dorsal spine in vertical direction. The region was
      separated into upper and lower sections by diaphragm. The upper section mainly
      contains heart and pericardium, while the lower contains broad ligament and left
      lobe of liver. The hiatus of diaphragm are vena caval foramen, esophageal foramen
      and aortic foramen in anterior-posterior turn. In the present study, 23 patients
      had portal hypertension, 18 had dissection of aorta, 8 got diseases in inferior
      vena cava, 9 had lymphoma, 12 got diseases in multiple vertebrae, 7 had lower
      thoracic esophageal carcinoma accompanied with metastasis in upper abdominal
      lymph nodes, 9 had carcinoma of abdominal esophagus and/or gastric cardia, 4 had
      esophageal hiatal hernia and 3 patients had neurogenic tumor in posterior
      mediastinum and/or superior spatium retroperitoneale. The MDCT features and
      distribution of the diseases in central thoracic-abdominal junctional region
      influence the anatomic-pathology characteristics in this region.

PMID- 22404004
TI  - [Experimental study of the effects of transesophageal oxygen saturation
      monitoring on the safety of esophageal mucosa].
AB  - The present paper was aimed to study the security of burning during the
      continuous monitoring of transesophageal arterial oxygen saturation. 20 rabbits
      were randomly divided into two groups: control group and high-frequency
      electrotome group. All rabbits were implanted with the oxygen saturation
      detection probes into the lower esophageal after anesthesia. The probes were made
      up with two light-emitting diode (LED) and then connected with oxygen saturation
      sensor to monitoring for 2h and 6h, respectively. We then intercepted two
      luminous points as esophageal specimens and dist the esophageal tissue detection
      device headend 1cm gastric side esophageal specimens (self-contr01) after
      monitoring, and carried out pathological examination. The pathological results of
      the LED-1, LED-2 esophageal biopsy and self-control section were mucous
      integrity, submucosal mildedema, hyperemia, a small number of lymphocytes and
      mononuclear cell infiltration. All the score of the esophageal tissue histologic
      was 2. The results showed that montioring the SteO2 not more than 6h was safe
      with montiored using a matching of oxygen saturation sensor and monitoring
      esophageal arterial oxygen saturation.

PMID- 22404005
TI  - [Research on the respiratory sinus arrhythmia in the process of guided
      breathing].
AB  - To investigate the effects of gradually guided breathing on respiratory sinus
      arrhythmia (RSA), 15 healthy men's simultaneous ECG and respiratory signals
      during the guided breathing process (14 beats/min-12.5 beats/ min--1 beats/min-
      9.5 beats/min--8 beats/minute--7 beats/min) were acquired. Based on the frequency
      domain and time domain methods, the effects of respiratory rate on RSA were
      studied. A general tendency increase features the three parameters of RSA as
      respiratory rate decreased. RSA represents the reflection control of respiratory
      system to cardiovascular system. The results suggested that the function of the
      reflection control of respiratory system to cardiovascular system increaseed with
      guided breathing decreasing. The conclusion indicates that the cardiovascular
      system could be improved by regulating the mode of respiration.

PMID- 22404006
TI  - [Correction of electrocardiogram signal baseline wander based on statistically
      weighted moving average filter].
AB  - Baseline wander (BW) is a common noise contaminating electrocardiogram (ECG). In
      order to effectively correct baseline of ECG signal and to preserve more latent
      components of ECG signal, this paper proposes a simple and novel filter based on
      statistically weighted moving average. Firstly, after the arrange between the
      maximum and the minimum of these sampling values in a moving window was divided
      into many sections with equal width, several segments [a(k), b(k)] including most
      samples were determined. Then, for every sample point in the moving window its
      weight was decided according to the criterion: its weight was set as 1 if the
      sampling value belongs to [a(k), b(k)], otherwise, as 0. Lastly, all these ECG
      sampling points with 1 weight were averaged to estimate the real baseline in the
      moving window. The algorithm was tested by simulated signal and real signal from
      www. physionet. org. The results showed that compared to traditional moving
      average filter and wavelet package (WP) translation, the proposed filter could
      more effectively correct baseline in ECG signal and result in less distortion to
      ECG signal.

PMID- 22404007
TI  - [Investigation of drawing region of interest in diffusion-weighted imaging
      between spinal tuberculosis and malignancy].
AB  - This study was aimed to evaluate the effect of region of interest (ROI) on
      measurement of apparent diffusion coefficient (ADC) obtained in diffusion
      weighted (DW) MR sequences between spinal tuberculosis and malignancy, selecting
      the more reasonable and effective measurement of ADC value. We collected the
      conventional MR sequences and diffusion-weighted imaging data of thirty-two
      patients with spinal tuberculosis or malignancy confirmed clinically and
      pathologically from August 2009 to June 2010. Using the conventional MRI as a
      guide, the signal intensity (SI) and ADC value were calculated by selecting
      single ROI and the same area multi-ROI within whole lesion at the largest slice
      of lesion respectively. Using ADC value defined by receiver operating
      characteristic (ROC) curve analysis as threshold, the sensitivity, specificity,
      and accuracy of ADC value for diagnosing spinal tuberculosis were compared. The
      results showed that the mean of ADC value at signal ROI was lower than that at
      the multi-ROI. There was no significant difference between the ADC value of
      single ROI and multi-ROI. The ADC values from spinal tuberculosis and spinal
      malignancy obtained in single ROI or multi-ROI showed significant differences.
      The sensitivity, specificity, and accuracy of ADC value for differentiating
      tuberculosis from neoplastic infiltration at signal ROI is lower than that at the
      multi-ROI. In conclusion, the ADC acquired multi-ROI can describe preferablywater
      molecular diffusion and is more useful in differentiating spinal tuberculosis
      from malignant bone marrow lesions.

PMID- 22404008
TI  - [The study of the domestic digital amplitude integrated EEG performance].
AB  - A total of 20 normal newborns and 8 brain injured newborns were monitored for 2
      hours with domestic digital amplitude integrated cerebral function monitor (CFM
      3000) and similar imported products LECTROMED CFM 5330 simultaneously. 32
      newborns with seizures or suspected seizures were monitored with CFM 3000 and
      conventional electroencephalogram (EEG) simultaneously. The tracings of amplitude
      integrated electroencephalogram (aEEG) monitored by CFM 3000 and LECTROMED CFM
      5330 are similar to each other. The continuous electrical activity, sleep-wake
      cycle, the mean of lower or upper bound voltage and duration of broad and narrow
      band were no significant statistical difference between different machines; The
      pattern of aEEG tracing of 8 infants with brain injury monitored by CFM 3000 was
      the same as monitored by the LECTROMED CFM 5330. The detection rate of seizure
      with CFM 3000 and conventional EEG were no statistically significant difference,
      and the consistency with Kappa test was: Kappa = 0.552, P = 0.001. The CFM 3000
      can reflect the change of cerebral function and identify infants with brain
      injury reliably.

PMID- 22404009
TI  - [Application of wavelet analysis in pick-up of breath signal from oscillations in
      chest wall].
AB  - In order to pick up breath signal from correlated noise background of the pulse
      of heart and artery etc, an algorithm based on wavelet de-noising has been
      introduced. With wavelet db4, the raw signal was decomposed into the scale space
      of six layers; threshold treatment was done with the self-adaptive threshold
      created by Stein's Unbiased Risk Estimate; then the wavelet coefficients were
      reconstructed. The result showed that the noise was significantly depressed.

PMID- 22404010
TI  - [MDCT and MRI findings of localized Castleman's disease and its pathological
      basis].
AB  - To evaluated the multi-detector CT (MDCT) and magnetic resonance imaging (MRI)
      features of localized Castleman's disease (CD), we retrospectively analyzed the
      clinical data, MDCT and MRI findings of 13 patients with CD proved
      pathologically. All patients underwent plain MDCT scan, 11 underwent enhanced CT,
      and 2 MRI. 14 lesions were detected in the 13 patients, and all of them were
      hyaline-vascular type (HV-CD) histopathologically. On plain MDCT scans, all
      lesions were homogeneously attenuated soft tissue mass; intra-tumoral
      calcification with punctate and "arborizing" patterns was detected in the center
      of 2 lesions each. Of the patients with enhanced MDCT, all lesions showed obvious
      enhancement homogeneously except two lesions with central stellate and 1 lesion
      with dotted low attenuation. Tortuous vessels could be revealed at the periphery
      of 8 lesions. Of the 2 patients with MRI, the lesions showed slightly hyper
      intensity on T1WI, hyper-intensity on T2WI and marked homogenous enhancement. In
      addition, one of them showed signal void appearance in the center on unenhanced
      MRI and large supplying artery with tortuous vessels at the periphery on enhanced
      MRI. In a word, Localized HV-CD usually demonstrated as soft tissue mass with
      obvious enhancement on MDCT and MRI. Central stellate area of low attenuation and
      calcification with punctate or "arborizing" pattern may also be present.

PMID- 22404011
TI  - [Comparison of calculation precision of photon dose between the two algorithms
      for the situation with air cavity and small fields].
AB  - In order to evaluate the calculation precision of the pencil beam (PB) algorithm
      and convolution-superposition(CS) algorithm for the situation with air cavity and
      small fields, we built a water phantom with an air cavity slab, in which the
      depth dose (DD) and off-axis ratio (OAR) for field 1cm x 1cm to field 7cm x 7cm
      were calculated by PB algorithms, CS algorithms and Monte Carlo (MC) simulation.
      The evaluation of algorithms by MC simulation was achieved by comparisons of DD
      with the spread penumbras of OAR curve self-defined as the width between isodose
      lines of 10% and 90%. It was shown that PB algorithm and CS algorithm both
      overestimated the DD but the degree overestimated by PB algorithm was more
      serious. The CS algorithm showed a better agreement with the MC simulation for
      the OARs, which spread to both laterals, while that was not predicted accurately
      by PB algorithm. It was indicated that PB algorithm and CS algorithm do not have
      high calculation precision whereas CS algorithms is relatively better for the
      situation with air cavity and small fields.

PMID- 22404012
TI  - [An analytic method of wavelet energy value to evaluate the contraction intensity
      of uterus].
AB  - The data of uterine contraction pressure is the information source for extracting
      uterine contractions status. Because there is a variety of interference existing
      in contraction pressure data, commonly used methods such as uterine contraction
      intensity integration method can not obtain decent evaluation results. We used
      the bior 2.4 biorthogonal wavelet to decompose and reconstruct the pressure data
      in order to obtain the best denoising effect. Combining with the denoised
      results, we proposed an algorithm of the wavelet energy value. Based on the
      algorithm, we calculated the curve of wavelet energy value. It was proved that
      using the curve of wavelet energy value can better identify contractions waveform
      and evaluation contractions intensity.

PMID- 22404013
TI  - [Validation for access recirculation and access flow rate measurement by contrast
      enhanced ultrasonography during hemodialysis].
AB  - To evaluate the feasibility and accuracy of contrast-enhanced ultrasonography
      (CEUS) for the measurement of hemodialysis access recirculation (AR) and access
      flow rate (Qa), a two pump system was used to simulate access and dialyzer flow.
      AR and Qa under different conditions, such as reversal connection of dialysis
      lines and the needle orientation, were compared with each other. The value of
      access flow and recirculation flow were calculated based on the formulas
      introduced in this paper, and the correlation and consistency between true flow
      rate and calculated values were analyzed. The measured R correlated well with
      true value of flow rate (r = 0.57, P = 0.038, Qa > Qb; r = 0.95, P = 0.001, Qa <
      Qb). The Bland-altman test showed good agreement between the calculated value
      based on CEUS and true values. The CEUS can be used as a new advanced technology
      for AR and Qa measurement.

PMID- 22404014
TI  - [Development of a portable high-power light-emitting diode phototherapy system
      for neonatal jaundice].
AB  - Our group have introduced a portable light emitting diode (LED) phototherapy
      system for treating neonatal jaundice. The device selects blue narrow-band LED as
      the light source, driven by MAX5035. The light intensity is linearly adjusted as
      the alteration of the pulse-width modulation signal, controlled by ATmega16L, and
      the value can be displayed in LCD12864. The device breaks the bonds of
      traditional phototherapy, it features small size and can provide an intense
      irradiance-controlled treatment as it's needed.

PMID- 22404015
TI  - [Establishment and application of mechanical strain loading system of multi
      channel cells].
AB  - Based on single-chip microcomputer, we have established a mechanical strain
      loading system with multi-channel to study the biological behavior of cultured
      cells in vitro under mechanical strain. We developed a multi-channel cell strain
      loading device controlled by single-chip microcomputer. We controlled the vacuum
      pump with vacuum chamber to make negative pressure changing periodically in the
      vacuum chamber. The tested cells were seeded on the surface of an elastic
      membrane mounted on the vacuum chamber, and could be strained or relaxed by
      cyclic pressure. Since the cells are attached to the surface of the membrane,
      they presumably experience the same deformation as that was applied to the
      membrane. The system was easy to carry and to operate, with deformation rate (1%
      21%) and frequency (0-0. 5Hz) which could be adjusted correctly according to
      experimental requirement, and could compare different deformation rate of three
      channels at the same time. The system ran stably and completely achieved design
      aims, and provided a method to study the biological behavior of cultured cells
      attached to the surface of the elastic membrane under mechanical strain in vitro.

PMID- 22404016
TI  - [Development and validation of a finite element model of human knee joint for
      dynamic analysis].
AB  - Based on the biomechanical response of human knee joint to a front impact in
      occupants accidents, a finite element (FE) model of human knee joint was
      developed by using computer simulation technique for impacting. The model
      consists of human anatomical structure, including femoral condyle, tibia condyle,
      fibular small head, patellar, cartilage, meniscus and primary ligament. By
      comparing the results of the FE model with experiments of the knee joint in axial
      load conditions, the validation of the model was verified. Furthermore, this
      study provides data for the mechanical of human knee joint injury, and is helpful
      for the design and optimization of the vehicle protective devices.

PMID- 22404017
TI  - [Numerical analysis on hemodynamics of cerebral aneurysm clip].
AB  - Computational fluid dynamics (CFD) was used to numerically investigate the blood
      flow in 3-D models of human preoperative and posteroperative of cerebral aneurysm
      clip, and the feasibility of surgical operation was evaluated by the calculated
      hemodynamics parameters. Mimics software was used to reconstruct the models from
      CT angiograms, and numerical simulation of blood flow at different time in a
      cardiac circle was performed. Comparison analysis of blood flow in three models
      of human preoperative and posteroperative of cerebral aneurysm clip was conducted
      in terms of blood velocity distribution, wall shear stress (WSS) distribution and
      pressure distribution. The results demonstrated that blood velocity and WSS were
      significantly increased, and pressure was obviously decreased.

PMID- 22404018
TI  - [Preparation of chitosan scaffold with different deacetylated degrees and
      evaluation of the degradation characteristics].
AB  - The chitosan scaffolds with different deacetylated degree were prepared in this
      study. The morphology of scaffolds were observed using SEM, and the porosity, the
      water absorbing swelling ratio and the degradation were examined both in vitro
      and in vitro. The results showed that the chitosan scaffolds with different
      deacetylated degree exhibited three-dimensional structure with high porosity.
      With increasing of deacetylated degree, their porosities were 93.46%, 90.02% and
      86.71%, respectively. The swelling ratios of chitosan scaffolds were 820%, 803%
      and 772%, respectively. At the fourth week, the degradation rates were 30.44%,
      22.08% and 17.10% in vitro, respectively; while the corresponding rates were
      57.48%, 40.23%, 29.53% in vivo respectively. The degradation rate of chitosan
      scaffold was negatively correlated to deacetylated degree. Furthermore, it showed
      that the speed of degradation in vivo was faster than that in vitro. We concluded
      that controlling the deacetylated degree of chitosan can provide a well-matched
      degradable scaffold material for the reparation of cartilage defects.

PMID- 22404019
TI  - [The analysis of the influencing factors of mortality rate in the transplantation
      of mouse bone marrow].
AB  - The purpose of the study was to investigate the influencing factors of mortality
      rate in the bone marrow transplantation in mice. The recipient mice receiving
      whole-body irradiation of gamma-ray were infused with the same strain of bone
      marrow cells or the mixture of the bone marrow cells and splenocytes
      respectively. Experiments were carried out in four batches, with different
      strains of mice used, respectively. The manifestations and the appearance of
      graft-versus-host disease (GVHD) were observed, as well as the mortality rate
      within 35 d of the transplantation in the recipient mice. The mortality rate of
      the first group of recipient mice was the lowest, the mortality rate of the
      second group of recipient mice was the highest and the obvious GVHD performance
      was observed before death. In the third group, the mortality rate declined and
      there was statistical significance compared to that of the second group. The
      mortality rate of the fourth group of mice was higher than that of the third
      group, but still lower than that of the second group of mice and there is a
      statistical significance. This evidence suggested that mouse genetic purity,
      splenocytes, the ratio of the bone marrow cells and splenocytes and the week-old
      of the mouse could be the important influencing factors of the mortality rate in
      mouse bone marrow transplantation.

PMID- 22404020
TI  - [Acqusition of full-length gene for rabbit osteoprotegerin].
AB  - This paper is to show a way of acqusition of the variable region gene of rabbit
      osteoprotegerin (OPG) and to analyse series. Total RNA was extracted from rabbit
      tibia, transcripted reversely into cDNA with random primers. The variable region
      of the OPG gene ampliflied using 5'RACE. Sequencing was confirmed by agarose gel
      electrophoresis and sequencing analysis. Full length of OPG gene was 1540bp that
      encoding 400 amino acids. It shared 89% identity with human OPG in whole amino
      acid sequence and about 85% with rattus norvegicus and other mammal. The OPG
      sequence of rabbit was obtained by 5'RACE, which could provide a good basis for
      OPG functional study.

PMID- 22404021
TI  - [Decision rules model for studying the law of compatibility of categorized
      formula based on rough set].
AB  - The theory of rough set was applied to the law of compatibility of categorized
      formulas research, and the decision rules model of the law of compatibility of
      categorized formulas was set up in order to explore the correlation between the
      compatibility of the categorized formula and the syndrome indexes. Based on this
      model, the core herbs of categorized formula were obtained through attribute
      reduction, the interaction of each herb in categorized formula could be analyzed
      by the effective decision rules, and the efficacy of the categorized formula
      could be predicted by decision rules. It would be very significant to optimize
      the compatibility of categorized formula and guide the clinical-practice.

PMID- 22404022
TI  - [Effects of superparamagnetic iron-oxide particles-labeling on the multi
      diffentiation of rabbit marrow mesenchymal stem cell in vitro].
AB  - The aim of this study was to label rabbit bone derived mesenchymal stem cells
      (BMSCs) with superparamagnetic iron oxide particles (SPIO) and to study the
      effects of magnetic labeling on the multi-differentiation of BMSCs. Rabbit BMSCs
      were isolated, purified, expanded, then coincubated with SPIO(25 microg/ml)
      complexed to protamine sulfate (Pro) transfection agents overnight. Prussian blue
      staining and transmission electron microscopy were performed to show
      intracellular iron. Cell differentiation was evaluated. Both labeled and
      unlabeled BMSCs were subjected to osteogenic, adipogenic and chondrogenic
      differentiation to assess their differentiation capacity for 21 d. Osteogenic
      cells were stained with alizarin red to reveal calcium deposition, adipogenic
      cells were stained with oil redO' respectively. Chondrogenic cells stained with
      Safranin-O, glycosamino glycans, and type II collagen production was assessed by
      standard immunohistochemistry. Cell with immunohistochemistry staining were
      detected by polarized light microscopy and analysed by Image-Pro Plus software.
      The results showed that intracytoplasmic nanoparticles were stained with Prussian
      blue and observed by transmission electron microscopy clearly except the
      unlabeled control. As compared with the nonlabeled cells, it showed no
      statistically significant difference on the differentiation of the labeled BMSCs.
      And the differentiation of the labeled cells were unaffected by the endosomal
      incorporation of SPIO. In summary, BMSCs can be labeled with SPIO without
      significant change in cell multi-differentiation capacity.

PMID- 22404023
TI  - [The study of beta2-adrenergic receptor gene polymorphism in Sanda athletes].
AB  - This study observed the disposition of beta2-adrenergic receptor (beta2-AR)
      Arg16Gly genotype and allele frequency among Sanda athletes in China, and
      investigated the diversity about the single nucleotide polymorphism of beta2-AR
      Arg16Gly between Sanda athletes and normal people of Han nationality in China. We
      used the technique of allele specified primer polymerase chain reaction to detect
      ADRB2 gene polymorphism of Sanda athletes (61 subjects) and normal Han nation
      people (50 subjects). The results showed there were significant differences about
      AA genotype, A allele, and G allele between Sanda athletes group and normal Han
      nation group (AA: chi2 = 6.646, P = 0.01, P < 0.05; A: chi2 = 4.003, P = 0.045, P
      < 0.05; G: chi2 = 4.003, P = 0.045, P < 0.05), and the frequency of AA genotype
      and A allele in the group of normal Han nation was higher than that in the group
      of Sanda athletes.

PMID- 22404024
TI  - [The influence shuxuetong on the membrane viscoelasticity of erythrocyte taken
      from patients with chronic pulmonary heart disease].
AB  - The present paper was aimed to explore the effect of Shuxuetong on the membrane
      viscoelasticity of erythrocyte taken from the acute phase patients suffering from
      chronic pulmonary heart disease. The membrane viscoelasticity of erythrocyte was
      taken from the acute phase patients suffering from chronic pulmonary heart
      disease. The changes of membrane viscoelasticity of erythrocyte after treated
      with shuxuetong were detected by micropipette aspiration technique. The results
      showed that the Shuxuetong of certain concentration could cause the decrease of
      membrane elastic modulus and viscous coefficients in acute phase patients
      suffering from chronic pulmonary heart disease. The study offers experimental
      evidences that the comprehensive treatment of pulmonary heart disease should
      involve the drug or measure to improve the erythrocyte deformability.

PMID- 22404025
TI  - [Enhancement of image used in optical imaging of intrinsic signal].
AB  - Optical imaging of intrinsic signals is a secondary image of the cerebral cortex.
      The weak optical signal is decided by anatomical structure of brain. The spatial
      filter is a powerful technology for de-noising and image enhancement. We used
      different linear and nonlinear filters to deal with optical imaging. Furthermore,
      we compared the degree of noise suppression and discussed the image details. Our
      result showed that nonlinear median filter can keep more image details with
      effective noise reduction. It is useful for image enhancement of optical imaging.

PMID- 22404026
TI  - [A new method to extract time-frequency characteristics of hypertension
      pathological signal based on pseudo Wigner-Ville distribution].
AB  - Hypertension, as one of diseases with the highest incidence in the world at
      present, is an important cause of stroke, coronary heart disease, renal
      insufficiency and other serious diseases. Based on pseudo Wigner-Ville
      distribution, this paper makes an analysis on the relevant pulse characteristics
      by measuring time range of the energy concentration circle. In view of the
      present situation, that is, about half of the high-normal blood pressure persons
      are likely to develop hypertension, we explored the pulse characteristics to find
      the pathological changes in subjects with prehypertension, in order to solve the
      problems that there are no obvious clinical significant features in
      prehypertension. The results showed that the duration of high energy circle in
      signal with hypertension pathological changes was shorter than the duration of
      healthy signal. Hence, healthy signal and hypertension pathological signal can be
      effectively distinguished by this method, and this provides a new basis to
      identify the lesion signal when blood pressure is in critical period.

PMID- 22404027
TI  - [Application of fuzzy reasoning to myocardial ischemia judgment based on
      electrocardiogram ST-T complex].
AB  - Electrocardiogram (ECG) is a convenient, economic, and non-invasive detecting
      tool in myocardial ischemia (MI). Its clinical appearance is mainly exhibited by
      ST-T complex change. MI events are usually instantaneous and asymptomatic in some
      cases, which cannot be forecasted to have a precautionary measure in time by
      doctors. The automatic detection of MI by computer and a cued warning of danger
      in real time play an important role in diagnosing heart disease. With the help of
      the medical staff, some quantitative approbatory indicators, such as ST-segment
      deviation, the amplitude of T-wave peak and the rate of ST and heart rate (HR),
      were combined to judge MI using fuzzy reasoning. After MIT-BIH database and the
      long-term ST database (LTST) verification, sensitivity and positive predictive
      values reached 75% and 78% respectively, and specificity and negative predictive
      values were 85% and 87% respectively. In addition, the proposed method was close
      to human way of thinking and understanding, and easy to apply in clinical
      detection and engineering fields.

PMID- 22404028
TI  - [A new method of automatic analysis of tongue deviation using self-correction].
AB  - The article analyzes the old analysis method of tongue deviation and introduces a
      new analysis method of it with self-correction avoiding the shortcomings of the
      old method. In this article, comparisons and analyses are made to current central
      axis extraction methods, and the facts proved that these methods were not
      suitable for central axis extraction of tongue images. To overcome the
      shortcoming that the old method utilized area symmetry to extract central axis so
      that it would lead to a failure to find central axis, we introduced a kind of
      shape symmetry analysis method to extract the central axis. This method was
      capable of correcting the edge of tongue root automatically, and it improved the
      accuracy of central axis extraction. In additional, in this article, a kind of
      mouth corner analysis method by analysis of variational hue of tongue images was
      introduced. In the experiment for comparison, this method was more accurate than
      the old one and its efficiency was higher than that of the old one.

PMID- 22404029
TI  - [Development of a multi-parameter and low-power monitor].
AB  - The development of a multi-parameter and low-power monitor is discussed in this
      paper. The monitor equips an AT91SAM9261 microprocessor as its main controller
      and contains multi-parameter signal collecting module, data storage module, human
      computer interaction module, online communications module and printing module.
      The whole software system is based on the uC/OS-II equipped by uC/GUI, which is
      used to facilitate interface design. At the same time, for the convenience of
      data management, a YAFFS2 file system is transplanted. The monitor has the
      advantages of low consuming, low cost, real-time control and multi-functions.

PMID- 22404030
TI  - [An annotation approach for masto-calcifications based on semantic model].
AB  - To realize the medical semantic annotation of mammogram, a semantic modeling
      approach for micro-calcifications in mammogram based on hierarchical Bayesian
      network (BN) was proposed. Firstly, support vector machines (SVM) were used to
      map low-level image feature into feature semantics, then high-level semantic was
      captured through fusing the feature semantics using BN. Finally semantic model
      was established. To validate the method, the model was applied to annotate the
      semantic information of mammograms. In this experiment, 142 images were chosen as
      training set and 50 images as testing set. The results showed that the accuracy
      of malignant samples was 81.48%, and that of benign samples was 73.91%.

PMID- 22404031
TI  - [Preparation for and study on the property of medical bacterial cellulose].
AB  - Bacterial cellulose (BC) was prepared by Acetobacter xylinum in static culture.
      After purified by chemical treatment, the microstructure, chemical structure,
      crystal structure and mechanical property of BC were characterized by scanning
      electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray
      diffractometry (XRD) and tensile strength measurement respectively, and compared
      with those of the imported bacterial cellulose wound dressing served as control
      sample (XBC). The results indicated that the diameter of the BC was (22 +/- 9)
      nm, and the crystallinity index was 89.71%. The tensile strength and the Young's
      mouduls of BC were significant higher than XBC both in wet and dry states. The
      biocompatibility of BC and XBC were evaluated by cytotoxicity test, delayed
      contact sensitization study in the Guinea Pig and skin irritation test. The
      results showed that BC had reliable biocompatibility as well as XBC. With the
      unique nanostructure, high crystallinity, high mechanical strength, and reliable
      biocompatibility, BC produced in our country as well as XBC can be used as a safe
      biomaterial for the medical applications.

PMID- 22404032
TI  - [Research on operating characteristics of multiclass receiver in machine
      learning].
AB  - The Receiver Operating Characteristic (ROC) curve has become a standard tool for
      the analysis and comparison of binary classifiers when the costs of
      misclassification are unknown. In fact ROC curve has replaced the correct rate or
      error rate. Extending this to the multiclass case has recently become a growing
      topic of interest. The conceptions and application of ROC curve are expounded.
      The history and some algorithms of the multi-class ROC surface are given in
      detail in this paper. Finally research trends of the multi-class ROC surface are
      approximating computing and visualization.

PMID- 22404033
TI  - [Development of dynamic ECG acquisition and recording system: review and
      prospect].
AB  - Dynamic electrocardiography (DCG) or Holter is the best device to detect
      arrhythmia and can help early detection of some sudden cardiac death risk
      factors. The acquisition and recording system of the DCG, however, affects the
      data quality and the patients' comfort directly. This paper reviews the related
      latest studies, and discusses the importance of new ECG electrode and wireless
      dynamic monitoring in DCG monitoring field. Moreover, the existed main problems
      are summarized and classified and the prospects for the development trend are
      presented.

PMID- 22404034
TI  - [EEG-fMRI studies on the neural networks of the generalized spike and wave
      discharges: an overview].
AB  - This paper generalizes the seizures characterized with paroxysmal generalized
      spike and wave discharges (GSWDs) in the EEG. Recent studies showed that GSWDs
      disrupt specific neural networks only rather than the entire brain homogenously.
      Simultaneous EEG and functional MRI (EEG-fMRDI) provides a high spatiotemporal
      resolution method for uncovering the regions of the brain showing changes in
      metabolism and blood flow during epileptic activity. Human EEG-fMRI studies to
      date have revealed the blood oxygenation level dependent (BOLD) signal changes in
      response to GSWDs in some specific brain regions. Most studies have noted similar
      BOLD signals decrease in the bilateral cortical regions including frontal,
      frontal-parietal, posterior cingulated and precuneus cortex, as well as in the
      basal ganglia, and BOLD signals increase in the bilateral thalamic. Further
      studies demonstrated that BOLD signals in different regions were dynamic changes
      in the time course of GSWDs and BOLD changes in the cortical areas occurred
      before in the thalamus. These cortical-subcortical structures may form the neural
      networks associated with GSWDs generation and maintenance. More sophisticated
      analytic techniques will be developed to explore the BOLD time-course of GSWDs
      and identify the brain structures involved in seizure onset and discharges
      propagation respectively. The sub-network associated with different behavioral
      deficits between interical and ictal GSWDs, and the different subtypes of
      generalized seizures will be further studied. The functional connectivity of the
      nodes of the neural network of GSWDs can also be further investigated. A better
      understanding of the neural network responsible for GSWDs generation may help to
      develop new therapeutic interventions.

PMID- 22404035
TI  - [Research on molecular mechanism of drug resistance of adefovir dipivoxil].
AB  - Adefovir dipivoxil (ADV) is a nucleotide anti-hepatitis B virus drug, which is
      able to effectively repress the replication of hepatitis B virus (HBV). ADV is a
      reverse transcriptase inhibitor. However, with the prolonged period of using,
      many kinds of HBV genetic mutants will occur and therefore resistance to ADV will
      be created. The purpose of this review is to draw the attention to the molecular
      mechanism of resistance to ADV.

PMID- 22404036
TI  - [Tissue development and construction and its regulational mechanism].
AB  - From the perspective of Regenerative Medicine, the tissue generated in vitro can
      imitate the physiological and pathological tissue to a certain extent. However,
      the structures and functions of the in vitro tissue are very simple so that
      research on in vitro self-assembling and imitating of tissue development is
      necessary. The development of Nanotechnology and the technology of micro
      structure makes the in vitro tissue assembling possible. As previous studies
      showed that, besides genetic material, tissue architecture and its micro
      environment are closely related to morphogenesis of in vitro tissue. Thus, how to
      design and assemble microstructure to make the tissue molding still requires
      effort. How to predict and control the development mechanism in vitro is also a
      question needed to be resolved. In this essay, we reviewed the mechanism of
      assembling and imitating of in vitro tissue based on the theory of physics,
      biology and systemic integrated structure.

PMID- 22404037
TI  - [Application of the quality evaluation of traditional Chinese herbal medicines
      using chromatography of fingerprints].
AB  - Chromatography of fingerprint as an important tool has been used in
      identification and quality control of herbal medicines, and it is gaining more
      and more attention. Among the various methods, chromatography gradually becomes
      the mainstream for its characteristics. This paper describes the techniques of
      chromatography of fingerprint including pretreatments for sample data set, the
      establishment of chromatographic fingerprint and fingerprint visualization. It
      emphasizes several analysis methods and their scope of application. Visualization
      technology combined with fingerprint makes analysis more intuitive. Finally,
      existing key problems and future works were also discussed.

PMID- 22404038
TI  - [Progress and application of sensors in medicine].
AB  - Sensors are apparatus that can percept specific matter information and change
      them into useful signals. They are widely used in medicine and are core
      components of medical equipments, and have become one of critical factors to
      accelerate the development of medicine. The applications of sensors in medical
      domain such as assistant examination, monitoring, treatment, disease prevention
      etc., and their progress tendency, were described detailedly in this article.

PMID- 22404039
TI  - Genome-wide analysis of cytogenetic aberrations in ETV6/RUNX1-positive childhood
      acute lymphoblastic leukaemia.
AB  - The chromosomal translocation t(12;21) resulting in the ETV6/RUNX1 fusion gene is
      the most frequent structural cytogenetic abnormality among patients with
      childhood acute lymphoblastic leukaemia (ALL). We investigated 62 ETV6/RUNX1
      positive childhood ALL patients by single nucleotide polymorphism array to
      explore acquired copy number alterations (CNAs) at diagnosis. The mean number of
      CNAs was 2.82 (range 0-14). Concordance with available G-band karyotyping and
      comparative genomic hybridization was 93%. Based on three major protein-protein
      complexes disrupted by these CNAs, patients could be categorized into four
      distinct subgroups, defined by different underlying biological mechanisms
      relevant to the aetiology of childhood ALL. When recurrent CNAs were evaluated by
      an oncogenetic tree analysis classifying their sequential order, the most common
      genetic aberrations (deletions of 6q, 9p, 13q and X, and gains of 10 and 21)
      seemed independent of each other. Finally, we identified the most common regions
      with recurrent gains and losses, which comprise microRNA clusters with known
      oncogenic or tumour-suppressive roles. The present study sheds further light on
      the genetic diversity of ETV6/RUNX1-positive childhood ALL, which may be
      important for understanding poor responses among this otherwise highly curable
      subset of ALL and lead to novel targeted treatment strategies.

PMID- 22404041
TI  - Strong adhesion and friction coupling in hierarchical carbon nanotube arrays for
      dry adhesive applications.
AB  - The adhesion and friction coupling of hierarchical carbon nanotube arrays was
      investigated with a hierarchical multiscale modeling approach. At device level,
      vertically aligned carbon nanotube (VA-CNT) arrays with laterally distributed
      segments on top were analyzed via finite element methods to determine the
      macroscopic adhesion and friction force coupling. At the nanoscale, molecular
      dynamics simulation was performed to explore the origin of the adhesion
      enhancement due to the existence of the laterally distributed CNTs. The results
      show interfacial adhesion force is drastically promoted by interfacial friction
      force when a single lateral CNT is being peeled from an amorphous carbon
      substrate. By fitting with experiments, we find that under shearing loadings the
      maximum interfacial adhesion force is increased by a factor of ~5, compared to
      that under normal loadings. Pre-existing surface asperities of the substrate have
      proven to be the source of generating large interfacial friction, which in turn
      results in an enhanced adhesion. The critical peeling angles derived from the
      continuum and nano- levels are comparable to those of geckos and other synthetic
      adhesives. Our analysis indicates that the adhesion enhancement factor of the
      hierarchically structured VA-CNT arrays could be further increased by uniformly
      orienting the laterally distributed CNTs on top. Most importantly, a significant
      buckling of the lateral CNT at peeling front is captured on the molecular level,
      which provides a basis for the fundamental understanding of local deformation,
      and failure mechanisms of nanofibrillar structures. This work gives an insight
      into the durability issues that prevent the success of artificial dry adhesives.

PMID- 22404040
TI  - A structural element that facilitates proton-coupled electron transfer in oxalate
      decarboxylase.
AB  - The conformational properties of an active-site loop segment, defined by residues
      Ser(161)-Glu(162)-Asn(163)-Ser(164), have been shown to be important for
      modulating the intrinsic reactivity of Mn(II) in the active site of Bacillus
      subtilis oxalate decarboxylase. We now detail the functional and structural
      consequences of removing a conserved Arg/Thr hydrogen-bonding interaction by site
      specific mutagenesis. Hence, substitution of Thr-165 by a valine residue gives an
      OxDC variant (T165V) that exhibits impaired catalytic activity. Heavy-atom
      isotope effect measurements, in combination with the X-ray crystal structure of
      the T165V OxDC variant, demonstrate that the conserved Arg/Thr hydrogen bond is
      important for correctly locating the side chain of Glu-162, which mediates a
      proton-coupled electron transfer (PCET) step prior to decarboxylation in the
      catalytically competent form of OxDC. In addition, we show that the T165V OxDC
      variant exhibits a lower level of oxalate consumption per dioxygen molecule,
      consistent with the predictions of recent spin-trapping experiments [Imaram et
      al. (2011) Free Radicals Biol. Med. 50, 1009-1015]. This finding implies that
      dioxygen might participate as a reversible electron sink in two putative PCET
      steps and is not merely used to generate a protein-based radical or oxidized
      metal center.

PMID- 22404042
TI  - Origin and fate of acetate in an acidic fen.
AB  - Acetate is a central intermediate in the anaerobic degradation of organic matter,
      and the resolution of its metabolism necessitates integrated strategies. This
      study aims to (1) estimate the contribution of acetogenesis to acetate formation
      in an acidic fen (pH ~ 4.9), (2) assess the genetic potential for acetogenesis
      targeting the fhs gene encoding formyltetrahydrofolate synthetase (FTHFS) and (3)
      unravel the in situ turnover of acetate using stable carbon isotope pore-water
      analysis. H(2)/CO(2)-supplemented peat microcosms yielded (13)C-depleted acetate
      (-37.20/00 vs. VPDB (Vienna Peedee belemnite standard) compared with -14.20/00
      vs. VPDB in an unamended control), indicating the potential for H(2)-dependent
      acetogenesis. Molecular analysis revealed a high diversity and depth-dependent
      distribution of fhs phylotypes with the highest number of operational taxonomic
      units in 0-20 cm depth, but only few and distant relationships to known
      acetogens. In pore waters, acetate concentrations (0-170 MUM) and delta(13)C
      values varied widely (-17.40/00 to -3.40/00 vs. VPDB) and did not indicate
      acetogenesis, but pointed to a predominance of sinks, which preferentially
      consumed (12)C-acetate, like acetoclastic methanogenesis. However, depth profiles
      of methane and delta(13)C(CH4) revealed a temporarily and spatially restricted
      role of this acetate sink and suggest other processes like sulfate and iron
      reduction played an important role in acetate turnover.

PMID- 22404043
TI  - Release kinetics of tocopherol and quercetin from binary antioxidant controlled
      release packaging films.
AB  - This paper investigated the feasibility of manipulating packaging polymers with
      various degrees of hydrophobicity to release two antioxidants, tocopherol and
      quercetin, at rates suitable for long-term inhibition of lipid oxidation in food.
      For example, one antioxidant can be released at a fast rate to provide short
      term/intermediate protection, whereas the other antioxidant can be released at a
      slower rate to provide intermediate/long-term protection of lipid oxidation.
      Controlled-release packaging films containing tocopherol and quercetin were
      produced using ethylene vinyl alcohol (EVOH), ethylene vinyl acetate (EVA), low
      density polyethylene (LDPE), and polypropylene (PP) polymers; the release of
      these antioxidants to 95% ethanol (a fatty food simulant) was measured using UV
      vis spectrophotometry, and Fickian diffusion models with appropriate initial and
      boundary conditions were used to fit the data. For films containing only
      quercetin, the results show that the release of quercetin was much faster but
      lasted for a much shorter time for hydrophilic polymers (EVOH and EVA) than for
      hydrophobic polymers (LDPE and PP). For binary antioxidant films containing
      tocopherol and quercetin, the results show that tocopherol released more rapidly
      but for a shorter period of time than quercetin in LDPE and EVOH films, and the
      difference is more pronounced for LDPE films than EVOH films. The results also
      show the presence of tocopherol can accelerate the release of quercetin. Although
      none of the films produced is acceptable for long-term lipid oxidation
      inhibition, the study provides encouraging results suggesting that acceptable
      films may be produced in the future using polymer blend films.

PMID- 22404044
TI  - The association of obesity with episodic and chronic migraine.

PMID- 22404046
TI  - Synthesis, crystal structures, and hydrogen-storage properties of Eu(AlH4)2 and
      Sr(AlH4)2 and of their decomposition intermediates, EuAlH5 and SrAlH5.
AB  - Complex Eu(AlH(4))(2) and Sr(AlH(4))(2) hydrides have been prepared by a
      mechanochemical metathesis reaction from NaAlH(4) and europium or strontium
      chlorides. The crystal structures were solved from powder X-ray diffraction data
      in combination with solid-state (27)Al NMR spectroscopy. The thermolysis pathway
      was analyzed in detail, allowing identification of new intermediate
      EuAlH(5)/SrAlH(5) compounds. Rehydrogenation experiments indicate that the second
      decomposition step is reversible.

PMID- 22404045
TI  - Hairless mutation: a driving force of humanization from a human-ape common
      ancestor by enforcing upright walking while holding a baby with both hands.
AB  - Three major characteristics distinguish humans from other primates: bipedality,
      practical nakedness, and the family as a social unit. A hairless mutation
      introduced into the chimpanzee/human last common ancestor (CLCA) 6 million years
      ago (Mya) diverged hairless human and hairy chimpanzee lineages. All primates
      except humans can carry their babies without using their hands. A hairless mother
      would be forced to stand and walk upright. Her activities would be markedly
      limited. The male partner would have to collect food and carry it to her by hand
      to keep her and their baby from starving; irresponsible and selfish males could
      not have left their offspring. The mother would have sexually accepted her
      partner at any time as a reward for food. Sexual relations irrespective of estrus
      cycles might have strengthened the pair bond. Molecular and paleontological
      dating indicates that CLCA existed 6 Mya, and early hominin fossils show that
      they were bipeds, indicating that humanization from CLCA occurred rapidly. A
      single mutation in animals with scalp hair is known to induce hairless phenotype
      (ectodermal dysplasia). Bipedalism and hairlessness are disadvantageous traits;
      only those who could survive trials and tribulations in cooperation with family
      members must have been able to evolve as humans.

PMID- 22404047
TI  - The assessment of the social cognition and object relations scale on TAT and
      interview data.
AB  - This study examines the reliability and convergent validity of 2 versions of the
      Social Cognition and Object Relations Scale (SCORS), one for use with Thematic
      Apperception Test narratives (SCORS-TAT; Westen, 1990) and one for use with
      clinical interview data (SCORS-CDI; Westen, Barends, Leigh, Mendel, & Silbert, 
      1990 ). Four SCORS dimensions were evaluated. Data were collected in a
      psychiatric sample (N = 74). Results show that although interrater reliability
      was good for all dimensions, internal consistency was low, especially for the
      affective dimensions. Structural equation modeling, in which a model with 2
      factors (i.e., SCORS-TAT and SCORS-CDI) and 4 dimensions each was tested,
      indicated low convergence between corresponding dimensions of SCORS-TAT and SCORS
      CDI. Correlational analyses suggested that this was due to a strong method
      factor. Regression analyses, however, revealed that the presence of a personality
      disorder operated as a moderator for convergence between corresponding cognitive
      structural dimensions.

PMID- 22404048
TI  - Preimplantation genetic diagnosis for HLA typing in a case of X-linked chronic
      granulomatous disease.
AB  - Bone marrow transplantation may be life saving in cases of hematopoietic disease,
      severe congenital immunodeficiency or malignancy. An HLA-matching sibling often
      gives the best success, but this may not be an option, nor may an HLA-matching
      unrelated donor be found. Preimplantation genetic diagnosis with HLA-matching
      embryos may then be a solution. We report the first Danish child born after such
      diagnosis with identification of healthy embryos and HLA matching for a sibling
      with chronic granulomatous disease. Our patient had 13 in vitro fertilization
      (IVF) cycles; 286 oocytes were collected and 74 embryos analysed. Sixteen of
      these (22%) were either healthy or carriers. Five embryos were transferred in
      four stimulated fresh IVF cycles. Four embryos were frozen, and two were later
      transferred. Two successive clinical pregnancies ensued. In the first, prenatal
      diagnosis revealed trisomy 21, and the fetus was aborted. In the second
      pregnancy, chorionic villus sampling revealed a normal karyotype, the diagnosis
      was confirmed, and the pregnancy was normal. At delivery, 82 mL of cord blood was
      collected for later transplantation to the diseased sibling.

PMID- 22404049
TI  - Rapid assessment breast clinic: how to offer the same day diagnosis?

PMID- 22404050
TI  - Fine needle aspiration cytology in symptomatic breast lesions: still an important
      diagnostic modality?
AB  - The objective of this study was to make an assessment of the utility of fine
      needle aspiration cytology (FNAC), in a "one-stop" symptomatic breast triple
      assessment clinic. Controversy surrounds the optimal tissue biopsy methodology in
      the diagnosis of symptomatic breast cancer and the identification of benign
      disease. FNAC in the context of a Rapid Assessment Breast Clinic (RABC) allows
      the same day diagnosis and early treatment of breast cancer, with the immediate
      reassurance and discharge of those with benign disease. We analyzed prospective
      data accrued at a RABC, over a 4-year period from 2004 to 2007. All patients were
      triple assessed, with FNACs performed on site by two consultant cytopathologists.
      Investigations were reported immediately, and clinical data were captured via a
      database using compulsory data field entry. There were 4487 attendances at our
      RABC, with 1572 FNACs were performed. The positive predictive value of FNAC with
      a C5 cancer diagnosis was 100%, 95.6% for a C4 report, with a complete
      sensitivity of 94%. The full specificity of correctly identified benign lesions
      was 77.4%, with a false negative rate of 3.85%. This enabled 66% of patients
      attending the RABC to receive a same day diagnosis of benign disease and
      discharge. FNAC is highly accurate in the diagnosis of symptomatic breast cancer
      in an RABC. FNAC allows accurate diagnosis of benign disease and immediate
      discharge of the majority of patients. In this era, when a large majority of
      patients have benign disease, we believe that FNAC provides an equivalent, if not
      better, method of evaluation of patients in a triple assessment RABC.

PMID- 22404051
TI  - Dermoscopy of early stage mycosis fungoides.
AB  - BACKGROUND: Early stage mycosis fungoides (MF) is difficult to be clinically
      differentiated from chronic dermatitis (CD) in a high proportion of patients.
      Dermoscopy is a rapid, cheep, non-invasive and widely used method for the
      evaluation of skin tumours and, recently, of inflammatory skin diseases, as well.
      OBJECTIVE: To describe the dermoscopic pattern of early stage MF and compare it
      with the dermoscopic features observed in CD. METHODS: This was a retrospective
      study. Dermoscopic images of lesions that were clinically equivocal between MF
      and CD were evaluated for the presence of predefined morphologic criteria.
      Diagnosis had been histopathologically and immunohistochemically confirmed in all
      cases. Sensitivity, specificity, positive predictive value, and negative
      predictive value were calculated for predefined dermoscopic criteria in relation
      to the diagnosis of mycosis fungoides. RESULTS: A total of 67 dermoscopic images
      were selected for dermoscopic evaluation. Mycosis fungoides lesions exhibited a
      characteristic dermoscopic pattern consisting of fine short linear vessels
      (sensitivity 93.7%, specificity 97.1%) and orange-yellowish patchy areas
      (sensitivity 90.6%, specificity 99.7%). A characteristic vascular structure
      resembling spermatozoa was also found to be highly specific for the diagnosis of
      mycosis fungoides. CD was typified by a different dermoscopic pattern, usually
      consisting of dotted vessels. CONCLUSIONS: These observations provide a first
      indication that early stage MF exhibits a characteristic dermoscopic pattern
      which is different from CD. Prospective studies with long term follow-up are
      needed to determine the value of these dermoscopic criteria in the
      differentiation between the two entities in the daily routine.

PMID- 22404053
TI  - To sleep, perchance to dream: continuity of care, handover and sleep in the
      intensive care unit.

PMID- 22404052
TI  - Unusual insertion and deletion at codon 67 and 69 of HIV type 1 subtype C reverse
      transcriptase among first-line highly active antiretroviral treatment-failing
      South Indian patients: association with other resistance mutations.
AB  - We report a high frequency of drug resistance mutations among patients with
      unusual insertions or deletions at the beta(3)-beta(4) hairpin-loop-coding region
      of HIV-1 subtype C reverse transcriptase, during failure of first-line
      antiretroviral therapy containing only reverse transcriptase inhibitors in
      Chennai, India.

PMID- 22404054
TI  - Registrar sleep patterns and supervision during two different rosters in a
      tertiary Australasian intensive care unit.
AB  - OBJECTIVE: To compare registrar sleep and supervision hours before and after a
      change in roster to accommodate more senior registrar (SR) positions, and to
      identify risky patterns of sleep on night shifts. DESIGN, SETTING AND
      PARTICIPANTS: Prospective study of 21 registrars on two different roster
      templates from September 2010 to May 2011 in the intensive care unit of
      Wellington Regional Hospital, Wellington, New Zealand. INTERVENTION: Roster
      change from 13 registrars and one SR to 10 registrars and four SRs. MAIN OUTCOME
      MEASURES: Mean sleep and supervision hours by shift; episodes of sleep <= 5
      hours, wakefulness >=17 hours, sleep during shift, waking before 16:00 before
      night shifts. RESULTS: 990 sleep surveys were analysed. There was no significant
      difference between groups in mean sleep or supervision hours for any shift. Two
      hundred and thirty-six night shifts were analysed. Registrars slept <=5 hours
      before 19/236 (8.1%) night shifts; had >=17 hours wakefulness before 79/236 night
      shifts (33.5%); woke by 16:00 107/ 236 (45.3%) times; and slept during 86/236
      (36.4%) night shifts. Registrars arrived at work having either woken before 16:00
      or had <=5 hours of sleep on 114/236 (48.3%) night shifts. CONCLUSIONS: Changing
      the registrar roster to meet the training demands of our senior trainees did not
      adversely affect registrar sleep or supervision. Registrars may be taking on
      unnecessary risk due to poor sleep hygiene around night shifts. We suggest sleep
      education and scheduled sleep time during night shifts.

PMID- 22404055
TI  - Deep vein thrombosis and pulmonary embolus in patients with traumatic brain
      injury: a prospective observational study.
AB  - BACKGROUND: Intensive care patients with traumatic brain injury (TBI) are at high
      risk of developing deep vein thrombosis (DVT). A high rate of DVT was reported
      before routine thromboprophylaxis, but the current DVT rate in TBI patients
      receiving best-practice mechanical and pharmacological prophylaxis is unknown.
      OBJECTIVES: To determine the prevalence of DVT among TBI patients. DESIGN,
      PARTICIPANTS AND SETTING: A prospective observational pilot study of adult
      patients admitted to the intensive care unit of a level 1 trauma centre within 72
      hours of sustaining a TBI (Glasgow Coma Scale score _14). MAIN OUTCOME MEASURES:
      Rate of DVT determined using twice-weekly compression ultrasound; rate of
      pulmonary embolism (PE) and length of stay. RESULTS: 36 patients (28 men; mean
      age, 40.3 years) were included. Six had moderate and 21 had severe TBI. Two
      patients (6%) developed a DVT and two patients (6%) developed a PE. The proximal
      leg DVT rate was 3%, but the overall venous thromboembolism rate was 11% (4
      patients). CONCLUSIONS: Mechanical and pharmacological prophylaxis appeared to be
      effective. The incidence of clinically identified PE is of concern and suggests
      that thromboembolic sources other than large leg veins may not be being
      adequately controlled by modern thromboprophylaxis regimens.

PMID- 22404056
TI  - The association between early arterial oxygenation and mortality in ventilated
      patients with acute ischaemic stroke.
AB  - BACKGROUND: There are conflicting data that suggest that hyperoxia may be
      associated with either worse or better outcomes in patients suffering a stroke.
      OBJECTIVES: To investigate the association between PaO(2) in the first 24 hours
      in the intensive care unit and mortality among ventilated patients with acute
      ischaemic stroke. DESIGN: Retrospective cohort study. SETTING: Data were
      extracted from the Australian and New Zealand Intensive Care Society Adult
      Patient Database. PARTICIPANTS: Adults ventilated for ischaemic stroke in 129
      ICUs in Australia and New Zealand, 2000-2009. MAIN OUTCOME MEASURES: The primary
      outcome was the odds ratio for in hospital mortality associated with "worst"
      PaO(2) considered as a categorical variable, with data divided into deciles and
      compared with the mortality of the 10th decile. For patients on an FiO(2) of _50%
      at any time in the first 24 hours, "worst" PaO(2) was defined as the PaO(2)
      associated with the highest alveolar-arterial (A-a) gradient. For patients on an
      FiO(2) of <50%, it was defined as the lowest PaO(2). Secondary outcomes were ICU
      and hospital length of stay and the proportion of patients in each decile
      discharged home. RESULTS: Of the 2643 patients eligible for study inclusion, 1507
      (57%) died in hospital. The median "worst" PaO(2) was 117mmHg (interquartile
      range, 87-196mmHg). There was no association between worst PaO(2) and mortality,
      length of stay or likelihood of discharge home. CONCLUSIONS: We found no
      association between worst arterial oxygen tension in the first 24 hours in ICU
      and outcome in ventilated patients with ischaemic stroke.

PMID- 22404057
TI  - Increased brain tissue oxygen tension in children with traumatic brain injury
      using temperature-corrected guided ventilation during prophylactic hypothermia.
AB  - OBJECTIVE: To investigate whether ventilatory management using a temperature
      corrected (pH-stat) or uncorrected (alpha-stat) blood gas analysis strategy
      improves brain tissue oxygen tension (PbrO(2)) in children prophylactically
      treated with moderate hypothermia for traumatic brain injury. DESIGN, SETTING AND
      PARTICIPANTS: Double crossover study conducted in the intensive care unit of a
      tertiary children's hospital. Nine children aged 3-14 years with severe traumatic
      brain injury were randomly allocated twice to a 6-hour period of either alpha- or
      pH-stat management while being kept hypothermic at 32.5 degrees C. MAIN OUTCOME
      MEASURES: PbrO(2), intracranial pressure (ICP) and PbrO(2)/PaO(2). RESULTS:
      PbrO(2) was significantly higher during pH-stat management (alpha-stat, 23.2mmHg
      [95% CI, 22.4- 24.0mmHg] v pH-stat, 28.7mmHg [95% CI, 27.9- 29.5mmHg]; P <
      0.001). PbrO(2)/PaO(2) was significantly higher during pH-stat (alpha-stat, 0.190
      [95% CI, 0.187- 0.193] v pH-stat, 0.251 [95% CI, 0.246-0.259]; P < 0.05). ICP was
      non-significantly higher during pH-stat (alpha-stat, 8.8mmHg [95% CI, 8.1
      9.5mmHg] v ph-stat,10.2mmHg [95% CI, 9.6-10.8]). CONCLUSION: PbrO(2) may be
      improved using a pH-stat blood gas management strategy in prophylactic
      hypothermia for paediatric patients with traumatic brain injury without any
      clinically relevant increase in ICP.

PMID- 22404058
TI  - Differences in mortality based on worsening ratio of partial pressure of oxygen
      to fraction of inspired oxygen corrected for immune system status and respiratory
      support.
AB  - OBJECTIVE: To define the relationship between worsening oxygenation status (worst
      PaO(2)/FiO(2) ratio in the first 24 hours after intensive care unit admission)
      and mortality in immunosuppressed and immunocompetent ICU patients in the
      presence and absence of mechanical ventilation. DESIGN: Retrospective cohort
      study. SETTING: Data were extracted from the Australian and New Zealand Intensive
      Care Society Adult Patient Database. PARTICIPANTS: Adult patients admitted to 129
      ICUs in Australasia, 2000-2010. MAIN OUTCOME MEASURES: In hospital and ICU
      mortality; relationship between mortality and declining PaO(2)/FiO(2) ratio by
      ventilation status and immune status. RESULTS: 457 750 patient records were
      analysed. Worsening oxygenation status was associated with increasing mortality
      in all groups. Higher mortality was seen in immunosuppressed patients than
      immunocompetent patients. After multivariate analysis, in mechanically ventilated
      patients, declining PaO(2)/FiO(2) ratio in the first 24 hours of ICU admission
      was associated with a more rapidly rising mortality rate in immunosuppressed
      patients than non-immunosuppressed patients. Immunosuppression did not affect the
      relationship between oxygenation status and mortality in non-ventilated patients.
      CONCLUSION: Immunosuppression increases the risk of mortality with progressively
      worsening oxygenation status, but only in the presence of mechanical ventilation.
      Further research into the impact of mechanical ventilation in immunosuppressed
      patients is required.

PMID- 22404059
TI  - Inadvertent sodium loading in critically ill patients.
AB  - BACKGROUND: Recommended daily intake of sodium is 1- 2mmol/kg. Sodium
      administration is rarely separated from fluid administration in critically ill
      patients. OBJECTIVE: To estimate the amount of sodium administered to patients
      who were invasively ventilated, and to investigate whether sodium administration
      affected oxygenation, length of stay in ICU and serum sodium level. DESIGN,
      PARTICIPANTS AND SETTING: Retrospective audit of adult patients who received
      invasive mechanical ventilation for >= 5 days in a tertiary-level intensive care
      unit. MAIN OUTCOME MEASURES: Total sodium administered from resuscitation and
      maintenance fluids, infusions, flushes, medicines, transfusions, enteral feeds
      and total parenteral nutrition; oxygenation, length of ICU stay and serum sodium
      level. RESULTS: 13 men and 7 women were included. Their median age was 71.9 years
      (range, 19.8-89.2 years). Median duration of mechanical ventilation was 9 days
      (range, 6-20 days) and median ICU stay 11.6 days (range, 6-21 days). Median
      APACHE II score was 29 (range, 18-41). Daily sodium administration was 225.5mmol
      (151-355mmol). The median daily net fluid balance was 351mL (range, - 759 to
      +1125mL) and median daily fluid intake was 2352mL (range, 1437- 3798mL). Daily
      sodium administered correlated with net fluid balance (P<0.001; r=0.35). Of total
      sodium administered, infusions contributed 22.2% (1.2%-39.9%); drugs 21.6% (0.0
      35.5%); flushes 17.4% (9.3%-24.5%); enteral feeds 17% (0.0-39.5%); resuscitation
      16.0% (2.5%-36.9%); maintenance fluids 5.8% (0.0-24.0%); transfusions 3.9% (0.0
      9.5%) and parenteral nutrition 0.1% (0.0-2.6%). CONCLUSION: Sodium administration
      to this cohort of critically ill patients requiring prolonged mechanical
      ventilation was high. Further studies should examine ways of limiting the amount
      of sodium administered to such patients and to examine if this influences patient
      outcomes.

PMID- 22404060
TI  - The effects of introduction of new observation charts and calling criteria on
      call characteristics and outcome of hospitalised patients.
AB  - OBJECTIVE: To determine the impact on call characteristics and patient outcomes
      since the implementation of a two-tiered rapid-response system along with new
      observation charts and calling criteria. DESIGN AND SETTING: A retrospective
      before-and-after study in an Australian tertiary referral hospital. PARTICIPANTS:
      Consecutive adult patients (_18 years), who had a rapid-response call between
      June and October 2009 ("before") and between June and October 2010 ("after").
      MAIN OUTCOME MEASURES: Incidence of "serious adverse events" (cardiac arrests,
      unexpected deaths, and unplanned intensive care unit/high-dependency unit [HDU]
      admissions); subsequent illness severity and ICU/HDU and hospital mortality and
      length of stay; episodes of repeat calls for the same patient, time since
      admission and treatment limitation/ not-for-resuscitation order profiles.
      RESULTS: Statistically significant increase in number of rapid response calls
      from 14.3 to 21.2 per 1000 hospital admissions before and after, respectively (P
      < 0.001); this was associated with a 16% decrease in composite serious adverse
      events (not significant). There were no significant differences in the number of
      unplanned ICU/HDU admissions, admission severity scores and subsequent ICU/HDU
      and hospital mortality and length of stay. There was a significant increase in
      number of calls for patients who were admitted to hospital within 24 hours (2.5 v
      4.7 per 1000 hospital admissions before and after, respectively; P < 0.05) and
      for patients who were transferred from acute care areas within 24 hours (3.7 v
      6.2 per 1000 hospital admissions before and after, respectively; P < 0.05). There
      was a significant increase in number of repeat calls for the same patient (1.6 v
      4.2 per 1000 hospital admissions before and after, respectively; P < 0.001); this
      was associated with higher mortality compared with single review in the after
      period (35.8% v 18.5%, respectively; P = 0.005). CONCLUSIONS: Implementation of a
      two-tiered rapid-response system and new observation charts and calling criteria
      increased the number of rapid-response calls with a nonsignificant trend towards
      a decreased incidence of serious adverse events. Further improvements in care of
      hospitalised patients may be possible by preventing repeat calls or calls within
      24 hours of hospital admission and discharge from acute care areas.

PMID- 22404062
TI  - Relationship between illness severity scores in acute kidney injury.
AB  - BACKGROUND: In the field of critical care nephrology, recent publications have
      used different illness severity scoring systems, making outcome comparisons
      difficult. OBJECTIVE: To establish a methodology to translate one illness
      severity scoring system into another for critically ill patients with acute
      kidney injury (AKI). DESIGN: Statistical analysis of prospectively obtained data.
      METHODS: Using data from the Australian and New Zealand Intensive Care Society
      Adult Patient Database, we obtained Acute Physiology and Chronic Health
      Evaluation (APACHE) II, APACHE III and Simplified Acute Physiology Score (SAPS
      II) scores for all patients admitted with AKI. We applied correlation and linear
      regression analyses as well as cross validation with hold out samples. RESULTS:
      Between 2001 and 2010, the three illness severity scores were obtained in 636 431
      admissions. Of these, 37 203 fulfilled the APACHE score criteria for AKI. The
      coefficient of determination (R2) between APACHE II and APACHE III scores was
      0.66. The overall model was APACHE III = 3.13 ? APACHE II + 7.99 (P < 0.001).
      Similarly, the R2 between APACHE III and the SAPS II scores was 0.78. The overall
      model was APACHE III = 1.49 ? SAPS II + 15.5 (P < 0.001). The R2 between APACHE
      II and SAPS II scores was 0.62. The overall model was APACHE II = 0.35 ? SAPS II
      + 9.3 (P < 0.001). CONCLUSIONS: Simple, robust translational formulae can be
      developed to allow clinicians to compare illness severity of patients with AKI
      when illness severity is expressed with different scoring systems.

PMID- 22404061
TI  - Statistical analysis plan for the Crystalloid Versus Hydroxyethyl Starch Trial
      (CHEST).
AB  - BACKGROUND: The Crystalloid Versus Hydroxyethyl Starch Trial (CHEST) is a 7000
      patient, multicentre, randomised controlled trial comparing the effects of 6%
      hydroxyethyl starch (130/0.4) to normal saline for fluid resuscitation in
      intensive care patients. The trial design is based on the Saline Versus Albumin
      Fluid Evaluation (SAFE) study and will be the largest fluid resuscitation trial
      conducted to date. OBJECTIVE: In accordance with two other trials conducted by
      the investigators, a predetermined statistical analysis plan (SAP) has been
      described and made public before completion of patient recruitment and data
      collection. The SAP will be adhered to for the final data analysis of this trial
      to avoid analysis bias arising from knowledge of study findings. METHODS: The SAP
      was designed by the chief investigators and statisticians and approved by the
      CHEST Management Committee. All authors were blind to treatment allocation and to
      the unblinded data produced during two interim analyses conducted by the Data
      Safety and Monitoring Board. The data shells were produced from a previously
      published protocol. Statistical analyses are described in broad detail.
      Specifically, information relevant to baseline characteristics and processes of
      care were defined, and statistically relevant descriptive elements described,
      with appropriate comparisons between groups. Trial outcomes were selected,
      categorised into primary, secondary and tertiary outcomes, and appropriate
      statistical comparisons between groups were planned and described. RESULTS: A
      standard SAP for CHEST was developed. A trial profile outline and list of mock
      tables were produced. Descriptions of analyses of baseline characteristics,
      processes of care, measures of efficacy and outcomes were described. Six
      prespecified subgroups were defined and statistical comparisons between groups in
      these subgroups were described. In addition, analyses of tertiary outcomes,
      including health economic and functional outcome assessment, were described.
      CONCLUSION: We have developed a predetermined SAP for CHEST. This plan accords
      with high-quality standards of internal validity to minimise analysis bias.

PMID- 22404063
TI  - Two cases of toxic methanol ingestion, one leading to brain death: case reports
      and a brief review.
AB  - Two patients were admitted sequentially to a rural emergency department, then
      transferred to a tertiary intensive care unit, both with serious methanol
      poisoning from home-brewed alcohol. They were intubated, mechanically ventilated,
      and treated with intravenous and nasogastric ethanol and continuous venovenous
      haemodiafiltration. Although quite similar in presentation, metabolic
      complications and therapy, one patient became brain dead due to severe cerebral
      oedema, while the other was discharged without any significant complications.
      Their course highlights the importance of early treatment of non-ethanol alcohol
      poisoning.

PMID- 22404064
TI  - A case of methylene chloride poisoning due to ingestion of home-distilled alcohol
      and potential new treatment with ethanol infusion.
AB  - We describe a case of a 51-year-old man who ingested methylene chloride and
      presented with the classical clinical features. He developed an acute abdomen
      that required repeated laparotomy. The effect of an ethanol infusion on
      carboxyhaemoglobin concentrations in this case was also of interest and could
      potentially be a new treatment modality.

PMID- 22404065
TI  - Respiratory care of patients with cervical spinal cord injury: a review.
AB  - Respiratory complications following cervical spinal cord injury are common and
      are the leading cause of morbidity and mortality after this type of injury.
      Impaired mechanics of ventilation, poor cough, increased secretions and
      bronchospasm predispose to atelectasis, pneumonia and exacerbations of
      respiratory failure. Prolonged mechanical ventilation and tracheostomy are often
      required. This review discusses the relevant pathophysiology, various ventilatory
      strategies and timing of tracheostomy, and examines the evidence surrounding
      physiotherapeutic and pharmacological treatment options.

PMID- 22404066
TI  - Paracetamol in critical illness: a review.
AB  - BACKGROUND: Paracetamol is one of the commonest medications used worldwide. This
      review was conceived as a consequence of evaluating the literature in the
      protocol development of two randomised, controlled clinical trials investigating
      the safety and efficacy of paracetamol in ICU patients (the HEAT [Permissive
      HyperthErmiA Through Avoidance of Paracetamol in Known or Suspected Infection in
      the Intensive Care Unit] study; the Paracetamol After traumatic Brain Injury
      [PARITY] Study). OBJECTIVE: To provide a historical perspective on the
      introduction of paracetamol into clinical practice, to present the pharmacology
      of paracetamol in critical illness, and evaluate the current evidence for its use
      as an antipyretic and analgesic in intensive care. DESIGN: Literature searches
      were performed using keywords: "paracetamol", "acetaminophen", "critical
      illness", "intensive care", "history", "pharmacology", "antipyre*", "analgesi*",
      "adverse effect*", "administration and dosage", "toxicity", "animals" and
      "humans". DATA SOURCES: Embase, MEDLINE, PubMed (1947/1950 to July 2011). REVIEW
      METHODS: The authors examined each article's title and abstract, fully reviewing
      relevant articles, with searching of reference lists and additional hand
      searching. The most recent and highest quality available evidence was included.
      RESULTS: Limited data are available on the pharmacology of paracetamol in the
      critically ill. Among patients with sepsis, paracetamol may inhibit the
      immunological response. Among patients with neurological injury paracetamol can
      reduce temperature but appears not to improve outcome. When administered with
      opioids after major surgery, paracetamol does not reduce the incidence of pain or
      opioid related side-effects. CONCLUSION: Despite the widespread use of
      paracetamol in critical illness, there is a paucity of data supporting its
      utility in this setting. Further research is required to determine how
      paracetamol should be used in the critically ill.

PMID- 22404067
TI  - Uncertainty in end-of-life care and shared decision making.
AB  - Assessing the appropriateness of continuing life support is a difficult task for
      intensive care unit staff. Part of this difficulty relates to prognostic
      uncertainty and the varying reliability of clinical decisions. Uncertainty about
      prognosis is quickly recognised by patients and families, and can be a source of
      mistrust and potential conflict. We discuss the reasons for uncertainty and
      outline key measures to reduce and manage such uncertainty. Practical certainty,
      where the clinicians are as certain as they can be, with both prognostication and
      knowledge of patient wishes, may be an appropriate concept for physicians engaged
      in end-of-life decisions. It involves accurate prognostication, informed
      surrogates, advance care planning, time to assess response, and the collective
      wisdom of experienced clinicians. The family conference should develop an agreed
      plan through shared decision making. The collective wisdom of experienced health
      care workers with good communication skills and informed patient advocates
      increases the likelihood of achieving practical certainty and the best decisions.
      However, greater time and effort seems to be required to improve end-of-life care
      in the ICU.

PMID- 22404068
TI  - Haemofiltration and high-frequency oscillatory ventilation in H1N1-induced acute
      respiratory distress syndrome.

PMID- 22404069
TI  - Are intensive care nurses really superior to the Confusion Assessment Method for
      the Intensive Care Unit (CAM-ICU) in detecting delirium?

PMID- 22404070
TI  - Intensive care unit delirium monitoring in Australia.

PMID- 22404072
TI  - Bedside electronic capture and conflicts of interest.

PMID- 22404074
TI  - Benchmarking participant recruitment in intensive care clinical trials.

PMID- 22404075
TI  - The landscape of drug discovery in atherosclerosis and dyslipidaemia revisited:
      an update of patenting activity.
AB  - INTRODUCTION: This paper is an update of a previous paper I published in Expert
      Opinion of Therapeutic Patents in 2008. The paper was a survey of patenting
      activity in the fields of atherosclerosis and dyslipidaemia, which identified
      trends in patenting by reviewing two major mechanistic categories,
      metabolic/dyslipidaemia and vascular/inflammation, as well as examining the
      interest in certain specific targets over a period of 10 years. METHODS: In this
      update, the same methodology was followed using the Espacenet of the European
      Patent Office (EPO) to identify patents claiming therapeutics for atherosclerosis
      or dyslipidaemia (excluding the wider metabolic syndrome). EXPERT OPINION: A
      major change in the field over the past 5 years has been the departure of larger
      companies from the field. This is reflected in the patenting activity. Patenting
      has been at a stable rate over the recent years with few new targets being
      highlighted. It is suggested that, for this field to return to the higher rates
      of patenting seen over 10 years ago, breakthroughs in translational medicine and
      in the ability to conduct clinical trials, particularly in biomarkers and
      imaging, will need to take place.

PMID- 22404076
TI  - Strategies for screening blood donors to source convalescent H1N1v plasma for
      intervention therapy.
AB  - BACKGROUND AND OBJECTIVES: During the 1918, pandemic blood components were
      successfully used to treat severe influenza pneumonia. A Proof of Principle trial
      investigating the clinical benefit of convalescent plasma was proposed in the
      2009 H1N1v epidemic with the aim of screening donors for high titre antibody in
      order to stockpile plasma packs to be used for treatment for severe pneumonia.
      MATERIALS AND METHODS: Serum samples were collected from donors. IgG antibody
      capture format enzyme-linked immunoassays using recombinant proteins (GACELISAs)
      were compared with microneutralization (MN) and haemagglutination inhibition
      (HAI). The influence of age and history of influenza-like illness (ILI) on the
      detection of high titre antibody was examined. RESULTS: 1598 unselected donor
      sera collected in October and December 2009 were tested by HAI. The HAI and
      demographic data defined a possible strategy for selective donor screening. One
      of the GACELISAs was highly specific for recent infection but showed lower
      sensitivity than HAI. CONCLUSIONS: During the 2009 pandemic screening 17- to 30
      year-old donors by HAI delivered around 10% with high antibody levels. The ELISA
      using a short recombinant H1N1v HA detected fewer reactives but was more specific
      for high titre antibody (>=1:256). Screening strategies are proposed based on
      using HAI on serum or GACELISA on plasma.

PMID- 22404077
TI  - Outbreak of hand, foot and mouth disease/herpangina associated with
      coxsackievirus A6 and A10 infections in 2010, France: a large citywide,
      prospective observational study.
AB  - Hand, foot and mouth disease (HFMD) and herpangina (HA) are frequently caused by
      several distinct serotypes belonging to the human enterovirus A species (HEVA).
      Enterovirus 71 is considered as a significant public health threat because of
      rare but fatal neurological complications. A sentinel surveillance system
      involving paediatricians from Clermont-Ferrand (France) was set up to determine
      the clinical and epidemiological characteristics of HFMD/HA associated with
      enterovirus infections. A standardized report form was used to collect
      demographic and clinical data. Throat or buccal specimens were obtained
      prospectively and tested for the presence of enteroviruses. The frequency of HEVA
      serotypes was determined by genotyping. Phylogenetic relationships were analysed
      to identify potential new virus variants. From 1 April to 31 December 2010, a
      total of 222 children were enrolled. The predominant clinical presentation was HA
      (63.8%) and this was frequently associated with clinical signs of HFMD (48%). An
      enterovirus infection was diagnosed in 143 (64.4%) patients and serotype
      identification was achieved in 141/143 (98.6%). The predominant serotypes were
      coxsackievirus A10 (39.9%) and A6 (28%), followed by coxsackievirus A16 (17.5%)
      and enterovirus 71 (6.3%). Fever was observed in 115 (80.4%) children. No patient
      had neurological complications. Coxsackievirus A10 and A6 strains involved in the
      outbreak were consistently genetically related with those detected earlier in
      Finland and constituted distinct European lineages. Although several enterovirus
      serotypes have been involved in HFMD/HA cases, the outbreak described in this
      population survey was caused by coxsackievirus A6 and coxsackievirus A10, the
      third dual outbreak in Europe in the last 3 years.

PMID- 22404078
TI  - Good morning creativity: task reactivation during sleep enhances beneficial
      effect of sleep on creative performance.
AB  - Both scientists and artists have suggested that sleep facilitates creativity, and
      this idea has received substantial empirical support. In the current study, we
      investigate whether one can actively enhance the beneficial effect of sleep on
      creativity by covertly reactivating the creativity task during sleep.
      Individuals' creative performance was compared after three different conditions:
      sleep-with-conditioned-odor; sleep-with-control-odor; or sleep-with-no-odor. In
      the evening prior to sleep, all participants were presented with a problem that
      required a creative solution. In the two odor conditions, a hidden scent-diffuser
      spread an odor while the problem was presented. In the sleep-with-conditioned
      odor condition, task reactivation during sleep was induced by means of the odor
      that was also presented while participants were informed about the problem. In
      the sleep-with-control-odor condition, participants were exposed to a different
      odor during sleep than the one diffused during problem presentation. In the no
      odor condition, no odor was presented. After a night of sleep with the
      conditioned odor, participants were found to be: (i) more creative; and (ii)
      better able to select their most creative idea than participants who had been
      exposed to a control odor or no odor while sleeping. These findings suggest that
      we do not have to passively wait until we are hit by our creative muse while
      sleeping. Task reactivation during sleep can actively trigger creativity-related
      processes during sleep and thereby boost the beneficial effect of sleep on
      creativity.

PMID- 22404079
TI  - Low expression of RECK indicates a shorter survival for patients with invasive
      breast cancer.
AB  - Expression cloning was used to initially isolate the reversion-inducing cysteine
      rich protein with Kazal motifs (RECK) gene as a suppressor of transformation. The
      gene was found to encode a membrane-anchored regulator of MMPs. Experimental
      studies showed that RECK can suppress tumor invasion, metastasis, and
      angiogenesis. However, the clinical impact of RECK remains unclear. To assess the
      clinical significance of RECK expression in invasive breast cancer, a total of
      119 patients with invasive breast cancer were retrospectively examined.
      Expression of RECK in tumor tissues was assessed by immunohistochemical staining.
      A significant correlation between RECK expression and 5-year survival rate was
      documented. The 5-year survival rate for patients with strong RECK expression was
      significantly higher than that for patients with weakly expressing tumors.
      Univariate and multivariate analyses confirmed that reduced RECK expression was
      an independent and significant factor in predicting a poor prognosis. In
      conclusion, RECK expression is a significant prognostic factor correlated with
      long-term survival for patients with invasive breast cancer. RECK expression is
      therefore a potentially useful prognostic marker for breast cancer.

PMID- 22404081
TI  - A preliminary report of the cost-effectiveness of tooth replacement strategies
      for partially dentate elders.
AB  - OBJECTIVE: To compare the cost-effectiveness of conventional treatment using
      partial dentures with functionally orientated treatment to replace missing teeth
      for partially dentate elders using a randomised controlled clinical trial.
      BACKGROUND: In many countries, including the Republic of Ireland, the only
      publically funded treatment option offered to partially dentate older patients is
      a removable partial denture. However, evidence suggests that these removable
      prostheses are unpopular with patients and can potentially increase the risk of
      further dental disease and subsequent tooth loss. MATERIALS AND METHODS: Fourty
      four partially dentate patients aged 65 years and older were recruited. Patients
      were randomly assigned to the two treatment arms of the study. The conventional
      treatment group received removable partial dentures to replace all missing
      natural teeth. The functionally orientated group was restored to a Shortened
      Dental Arch (SDA) of 10 occluding contacts using resin-bonded bridgework (RBB).
      The costs associated with each treatment were recorded. Effectiveness was
      measured in terms of the impact on oral health-related quality of life (OHRQoL)
      using OHIP-14. RESULTS: Both groups reported improvements in OHRQoL 1 month after
      completion of treatment. The conventional treatment group required 8.3 clinic
      visits as compared to 4.4 visits for the functionally orientated group. The mean
      total treatment time was 183 min 19 s for the conventional group vs. 124 min 8 s
      for the functionally orientated group. The average cost of treatment for the
      conventional group was 487.74 Euros compared to 356.20 Euros for the functional
      group. CONCLUSIONS: Functionally orientated treatment was more cost-effective
      than conventional treatment in terms of treatment effect and opportunity costs to
      the patients' time.

PMID- 22404082
TI  - The influence of cardiovascular risk factors on bone marrow mesenchymal stromal
      cell fitness.
AB  - BACKGROUND AIMS: In the past, cell transplantation strategies for the treatment
      of heart failure have shown promising results in experimental and clinical
      studies. Bone marrow (BM)-derived stem cells represent the most frequently used
      cell population. Within this heterogeneous cell population, mesenchymal stromal
      cells (MSC) have been identified to induce therapeutic effects, mainly through
      paracrine mechanisms. Because of their low frequency in native tissues, in vitro
      cell culture expansion is mandatory prior to transplantation. We sought to
      identify patient-specific cardiovascular risk factors influencing the
      proliferative potential of MSC. METHODS: BM aspirates from 51 patients undergoing
      elective cardiac surgery were analyzed for MSC frequency and cell culture
      expansion potential. Fibroblastic colony-forming units (CFU-F) were quantified
      for culture conditions applying autologous (AS) or fetal bovine serum (FBS) and
      different basic media. Univariate and multivariate analyzes were performed in
      order to determine the impact of patient-specific factors on CFU-F numbers.
      RESULTS: Expanded MSC showed a specific immune phenotype and displayed
      adipogenic, chondrogeneic and osteogeneic differentiation potential. CFU-F
      numbers did not differ under AS or FBS supplementation. Elevated numbers of
      mononuclear cells, diabetes mellitus, steroid treatment, chronic obstructive
      pulmonary disease, renal failure, high euroSCORE and impaired left ventricular
      function were significant determinants for higher CFU-F numbers. CONCLUSIONS: The
      impact of specific cardiovascular risk factors on MSC fitness could be
      determined. These results may help to establish patient profiling in order to
      identify patients suitable for autologous MSC transplantation, and might lead to
      the identification of disease-related mechanisms of stem cell activation.

PMID- 22404083
TI  - Therapeutic effects of human amniotic epithelial stem cells in Niemann-Pick type
      C1 mice.
AB  - BACKGROUND AIMS: Niemann-Pick disease type C1 (NPC) is an autosomal recessive
      cholesterol-storage disorder characterized by liver dysfunction,
      hepatosplenomegaly and progressive neurodegeneration. Thus far, studies of NPC
      mice have been performed mainly to study the brain and neurodegeneration, because
      degeneration in the brain was known as the primary cause of death in NPC mice.
      However, NPC is a systemic disease; therefore the purpose of this study was to
      find the possibility of a general therapeutic effect by applying and tracking
      transplanted human amniotic epithelial stem cells (hAESC) in NPC mice. METHODS:
      hAESC were administered to NPC homozygous (NPC(-/-)) mice via intravenous
      injection from 5 weeks of age; each recipient received 5 * 10(5) cells every
      other week. The body weight of each of the mice was measured every week, and the
      survival and state of each mouse was evaluated every day. The weight of the
      organs was measured, and serum chemistry, histology and the intensity of Filipin
      staining were evaluated. RESULTS: The effect of cell transplantation was to
      extend the life span and reduce the rapid loss of weight. Moreover, alleviation
      of tissue damage was observed more in hAESC-treated NPC(-/-) mice than in non
      treated NPC(-/-) mice. Cholesterol deposition was reduced after transplantation,
      and the relative weight of the liver was also decreased. CONCLUSIONS: These data
      show that hAESC could delay the degeneration caused by fatal genetic disorders
      such as NPC. This study presents the prospect of relief of precipitous disease
      progression and the therapeutic possibility of applying hAESC to fatal genetic
      disorders.

PMID- 22404084
TI  - Clinical-grade varicella zoster virus-specific T cells produced for adoptive
      immunotherapy in hemopoietic stem cell transplant recipients.
AB  - BACKGROUND AIMS: Varicella zoster virus (VZV) causes life-long latent infection
      in healthy individuals, which reactivates in 10-68% of stem cell transplant
      patients. Reconstituting immunity through adoptive transfer of T cells specific
      for VZV may aid in the prophylaxis and treatment of VZV infections. The potential
      for generating T cells specific for VZV using a clinically approved VZV vaccine
      strain was investigated. METHODS: The Varivax(r) vaccine was used to stimulate
      peripheral blood mononuclear cells from healthy donors. Only reagents approved
      for clinical manufacture were used. Monocyte-derived dendritic cells pulsed with
      Varivax (R) were used to stimulate autologous mononuclear cells at a responder to
      stimulator ratio of 10:1. On day 7, a second stimulation was performed; 20 U/mL
      interleukin (IL)-2 were added from day 7 and 50 U/mL IL-2 from day 14 onwards.
      Cell phenotype and functionality were assessed after 21 days of culture. RESULTS:
      A mean increase of 11-fold in cell number was observed (n= 18). Cultures were
      mainly T cells (mean CD3 (+) 89.7%, CD4 (+) 54.2%, CD8 (+) 28.7%) with effector
      and central memory phenotypes. Cells produced one or more T helper (Th)1 cytokine
      (interferon-gamma, tumor necrosis factor-alpha and IL-2), and CD4 (+) (but not
      CD8 (+) ) cells expressed the cytoxicity marker CD107 when restimulated with VZV
      antigens. CONCLUSIONS: We have demonstrated a clinically applicable method that
      yields high numbers of highly reactive T cells specific for VZV. We propose that
      reconstructing host immunity through adoptive transfer of VZV-specific T cells
      will reduce the frequency of clinical VZV infection in the period of severe
      immune suppression that follows allogeneic stem cell transplantation.

PMID- 22404086
TI  - Identification of feeding risk factors for impaired nutrition status in
      paediatric patients with cerebral palsy.
AB  - AIM: To assess the nutrition status of children with CP, applying WHO growth
      standards, to indentify feeding risk factors and to evaluate their impact on the
      growth of children with CP. METHODS: In 42 paediatric patients (mean age 8.00 +/-
      4.00 years), anthropometry and food intake records were assessed. z-scores were
      calculated using WHO Anthro software. Intake to requirements ratio (I/R) was
      calculated, and patients were classified according to their feeding ability
      (PFA). Overall diet quality was assessed using the Diet Quality Index
      International (DQI-I). RESULTS: Based on WAz, 15 patients (38.1%) were
      undernourished. No association was found between I/R ratio and BMI z-score, while
      PFA and DQI-I displayed a significant correlation to both (p < 0.05). Diet
      Quality Index International was also correlated with macronutrient distribution
      (p < 0.05). Patients with CP were undernourished in a considerable proportion.
      Malnutrition in patients with CP is not associated with the intake of estimated
      energy requirements. Among the other feeding risk factors studied, PFA and DQI-I
      represented important parameters associated with malnutrition. CONCLUSION: WHO z
      scores represent accurate parameters for the assessment of malnutrition in
      patients with CP. Together with anthropometry and PFA evaluation, the use of the
      DQI-I would add prognostic value to both the initial growth assessment and the
      patients' growth monitoring.

PMID- 22404087
TI  - Epigenetic Myopia: Rx Control It! Epipha-Me Globe Re-Fixes with IOA III.

PMID- 22404085
TI  - Relation over time between facial measurements and cognitive outcomes in fetal
      alcohol-exposed children.
AB  - BACKGROUND: The identification of individuals exposed prenatally to alcohol can
      be challenging, with only those having the characteristic pattern of facial
      features, central nervous system abnormality, and growth retardation receiving a
      clinical diagnosis of fetal alcohol syndrome (FAS). METHODS: Seventeen
      anthropometric measurements were obtained at 5 and 9 years from 125 Cape Town,
      South African children, studied since birth. The children were divided into 3
      groups: FAS or partial FAS (PFAS), heavily exposed nonsyndromal (HE), and non
      alcohol-exposed controls (C). Anthropometric measurements were evaluated for mean
      group differences. Logistic regression models were used to identify the subset of
      anthropometric measures that best predicted group membership. Anthropometric
      measurements were examined at the 2 ages in relation to prenatal alcohol exposure
      obtained prospectively from the mothers during pregnancy. Correlation of these
      facial measurements with key neurobehavioral outcomes including Wechsler
      Intelligence Scales for Children-IV IQ and eyeblink conditioning was used to
      assess their utility as indicators of alcohol-related central nervous system
      impairment. RESULTS: Significant group differences were found for the majority of
      the anthropometric measures, with means of these measures smaller in the FAS/PFAS
      compared with HE or C. Upper facial widths, ear length, lower facial depth, and
      eye widths were consistent predictors distinguishing those exposed to alcohol
      from those who were not. Using longitudinal data, unique measures were identified
      that predicted facial anomalies at one age but not the other, suggesting the face
      changes as the individual matures. And 41% of the FAS/PFAS group met criteria for
      microtia at both ages. Three of the predictive anthropometric measures were
      negatively related to measures of prenatal alcohol consumption, and all were
      positively related to at least 1 neurobehavioral outcome. CONCLUSIONS: The
      analysis of longitudinal data identified a common set of predictors, as well as
      some that are unique at each age. Prenatal alcohol exposure appears to have its
      primary effect on brain growth, reflected by smaller forehead widths, and may
      suppress neural crest migration to the branchial arches, reflected by deficits in
      ear length and mandibular dimensions. These results may improve diagnostic
      resolution and enhance our understanding of the relation between the face and the
      neuropsychological deficits that occur.

PMID- 22404088
TI  - Bupivacaine injection myotoxicity on extraocular muslces. A strabismus
      alternative treatment: extended histological changes induced in a rabbit model.
AB  - PURPOSE: To evaluate longer term histological changes of extraocular muscles
      induced by bupivacaine toxicity. METHODS: The superior rectus and inferior rectus
      of white rabbits were injected with 0.4 mg of agent in 0.3 ml of bupivacaine.,
      Then, histological changes of these rectus muscles were examined at 1,2,4 and 8
      weeks after injection. RESULTS: Bupivacaine injection induced myotoxic changes in
      both orbital and global layers. Regenerating myofibers were found at 1 week after
      injection. These changes were reduced by 4 weeks post injection. At 4 weeks
      increasing muscle fiber size in both orbital and global layer were seen. There
      was no scar formation after 8 weeks post injection. CONCLUSIONS: Extraocular
      muscle bupivacaine injection can cause acute myonecrosis followed with
      regeneration. After 8 weeks the muscles recovered with arranged myofibers almost
      at normal level. However we found increased myofiber diameter at 4 weeks after
      injection which was remained stable until 8 weeks post injection, Further
      investigation about functional change in these muscles is needed to facilitate
      application of this methodology.

PMID- 22404089
TI  - Review: oculomotor cranial nerve palsies: symptoms, problems and non-surgical
      preoperative management of the resultant complex incomitant strabismus and
      monocular and binocular vision disturbances.
AB  - The purpose of this presentation is first to describe the symptoms and problems
      encountered in cranial nerve palsies (CNP). The purpose is also to describe the
      different means of treatment during the observational preoperative period and
      their positive or negative impact on each of the symptoms and problems. Finally,
      we will present our way of handling these patients in their preoperative period:
      practical, inexpensive, and unsophisticated means that keep the patient
      comfortable and prevent the secondary untoward effects that can take place.

PMID- 22404090
TI  - History of medicine: ocular disorders of the mona lisa (strabismus) and other
      famous paintings in the louvre, paris.
AB  - The History of Medicine and Medical Specialties such as Ophthalmology, and the
      Subspecialty of Strabology extend back to the beginning of recorded history.
      Before there was photography to record physical abnormalities of living
      creatures, there was art and artists who did the recording in their works.
      Fortunately, many such recordings have been preserved, usually in museums, such
      as the Louvre, in Paris, France. They provide the graphic evidence of the same
      medical problems which our ancestors suffered and survived which we still do but
      now understand and can ameliorate better. The purpose of this paper is to provide
      several examples of these art works, to illuminate these historical aspects of
      medicine.

PMID- 22404091
TI  - Left-Sided Predominance in Pseudo-esotropia.
AB  - Pseudo-strabismus, or more precisely, pseudo-esotropia, is commonly encountered
      in pediatric ophthalmology. In our practice, the left eye was reported by parents
      as being deviated more frequently than the right eye. We attribute this
      laterality to the fact that most  parents are right handed. They therefore tend
      to hold their children with their left  arm, and to feed them with their right
      hands, in both cases viewing the left eye of the child in the adducted position.

PMID- 22404092
TI  - Successful extraocular muscle re-resection for a strabismus surgery complication:
      a "snapped" [severed, inadvertently] and retrieved inferior rectus muscle: a case
      report.
AB  - A 26- year-old woman who had a left head tilt since childhood was undergoing left
      inferior rectus resection to correct  her left inferior rectus paresis.  During
      the surgery, when the inferior rectus was isolated and engaged with an eye muscle
      hook, the muscle tore (snapped) completely into two pieces, 8 mm posterior to
      insertion. Fortunately, we were able to find the proximal portion of the muscle
      and, after a 3 mm resection, of the distal yet attached 8 mm portion, the
      proximal and distal portions were sutured together with a non-absorbable suture. 
      After nine months followup there was significant diplopia, and the preoperative
      left head tilt and left hypertropia remained, so a left inferior rectus re
      resection was done.  At the end of 18 months  followup after the second procedure
      there was no binocular deviation (strabismus) in primary position nor in any
      other gaze positions, but there was a mild ocular motility infraduction deficit 
      present on left and down gaze.

PMID- 22404093
TI  - Stage III Intraoperative Adjustmentof Eye Muscle Surgery (Under General
      Anesthesia) for Neuroparalytic and Mechanical (Restrictive) Incomitant
      Strabismus: Report of Results in a Series: Outcomes in 20 Eye Muscle Surgeries in
      Twelve Patients.
AB  - Techniques for the adjustment of surgery intraoperatively (especially those
      termed Stage I and II techniques) have proven maximally successful in improving
      surgical results for comitant strabismus. Stage III adjustments (end-operative)
      have been described but not studied. In a retrospective study of 20 eye muscle
      procedures in 12 patients with neuroparalytic and mechanical strabismus, the
      usefulness of various intraoperative adjustment techniques Stage I, II, and III
      was investigated for the first time. Stage I adjustments (adjusting the surgical
      plan based on the binocular misalignment following induction) were not helpful.
      Stage II adjustments (R. Bedrossian technique: adjusting the amount of surgery
      performed to create an actual change in binocular alignment under anesthesia 
      matching the change in alignment desired clinically) were appropriate for
      horizontal mechanical and (all) vertical cases but not appropriate for horizontal
      neuroparalytic cases. Stage III adjustments, at the end of surgery, were
      appropriate in virtually all cases (20 muscles, 12 patients). Significant
      overcorrection, well beyond the theoretically ideal final intraoperative
      binocular alignment of 30 PD (prism diopters) was appropriate in all cases, but
      varied with type of case. Verticals (all) required a 5-10 PD overcorrection.
      Horizontal mechanical cases required a 22-30 PD overcorrection. Horizontal
      neuroparalytic cases required a 15-38 PD overcorrection, in the last group, in 
      each case, graded according to the presence of contractures and the size of the
      preoperative deviation. The use of Stage III (and Stage II as noted above)
      adjustments brought postoperative binocular alignment to orthotropia +/- 10 PD in
      all cases, the conventional standard for satisfactory results in strabismus
      surgery.

PMID- 22404094
TI  - Consciousness: A Function of Stereoscopic Vision via the Egocenter; Continued.

PMID- 22404095
TI  - Game interruptions in elite soccer.
AB  - The objectives of the study were to analyse game interruptions of league soccer
      in detail and the tactical use of game interruptions. Sixteen matches of a German
      first league soccer team were observed. An observational system was designed to
      assess interruption types, score, duration of interruption, location of
      interruption, time of interruption and number of occurrences. Results showed that
      there is an average of 108 interruptions per match. Throw-ins (40) and free kicks
      (33) were most frequent. Goal kicks (17), corner kicks (10), substitutions (4),
      and kick offs (3) occurred less often. Drop balls, penalties, and injuries
      occurred least often. For 38% of the total match time observed, matches were
      halted. The mean duration of running and interrupted match parts were 32.1 s and
      18.7 s, respectively. The analysis showed significant differences concerning the
      influence of the location of interruption, score, and time of interruption on the
      duration of different interruption types (P < 0.05). The results of the study
      showed the tactical use of game interruptions during league soccer matches, e.g.
      goal kicks of the leading team take longer towards the end of the match.
      Examining game interruptions has turned out to be a valuable source of
      information adding to our knowledge of soccer. We have shown evidence that the
      durations of many interruptions serve tactical purposes, a well-known hypothesis
      in practice.

PMID- 22404096
TI  - Impact of family history of diabetes on beta-cell function and insulin resistance
      among Chinese with normal glucose tolerance.
AB  - OBJECTIVE: This study investigated the impact of family history of diabetes (FHD)
      on beta-cell function among Chinese with normal glucose tolerance. RESEARCH
      DESIGN AND METHODS: A multistage, stratified, cluster random sampling method was
      used to select a provincially representative sample from Fujian Province.
      Eventually, a total of 1,183 subjects were entered into the analysis. Several
      indexes were used to assess the function of beta cells, including homeostasis
      model assessment (HOMA) of insulin resistance (IR), HOMA of beta cells,
      insulinogenic index (IGI), and disposition index. RESULTS: Overweight, increased
      body mass index, higher low-density lipoprotein cholesterol, and higher total
      cholesterol (TC) were the dominant features of positive FHD (FHD(+)). The FHD(+)
      subjects had lower insulin sensitivity (P<0.05). FHD(+) subjects showed higher
      risk of IR after adjusting for other risk factors (odds ratio 1.523 [1.272
      2.009]). However, there was no significant difference in insulin secretion
      between the two groups. With the use of the multiple linear regression model,
      waist circumference (WC) and triglycerides (TGs) were found to be independent
      risk factors of the decline of insulin sensitivity in FHD(+) subjects, and
      insulin sensitivity declined significantly (P<0.05) with the increase of WC and
      TGs. In addition, the offspring of fathers with diabetes (PT2D) were much older
      and had higher TC than those of mothers with diabetes (MT2D). After adjusting for
      gender of the parents, there was no difference between MT2D and PT2D on insulin
      sensitivity. CONCLUSIONS: Inheritance if diabetes is associated with the decline
      of insulin sensitivity. In addition, insulin sensitivity declined with increasing
      WC and TG in FHD(+) subjects.

PMID- 22404097
TI  - Quinazoline derivatives as potential anticancer agents: a patent review (2007 -
      2010).
AB  - INTRODUCTION: Due to the increase in knowledge about cancer pathways, there is a
      growing interest in finding novel potential drugs. Quinazoline is one of the most
      widespread scaffolds amongst bioactive compounds. A number of patents and papers
      appear in the literature regarding the discovery and development of novel
      promising quinazoline compounds for cancer chemotherapy. Although there is a
      progressive decrease in the number of patents filed, there is an increasing
      number of biochemical targets for quinazoline compounds. AREAS COVERED: This
      paper provides a comprehensive review of the quinazolines patented in 2007 - 2010
      as potential anticancer agents. Information from articles published in
      international peer-reviewed journals was also included, to give a more exhaustive
      overview. EXPERT OPINION: From about 1995 to 2006, the anticancer quinazolines
      panorama has been dominated by the 4-anilinoquinazolines as tyrosine kinase
      inhibitors. The extensive researches conducted in this period could have caused
      the progressive reduction in the ability to file novel patents as shown in the
      2007 - 2010 period. However, the growing knowledge of cancer-related pathways has
      recently highlighted some novel potential targets for therapy, with quinazolines
      receiving increasing attention. This is well demonstrated by the number of
      different targets of the patents considered in this review. The structural
      heterogeneity in the patented compounds makes it difficult to derive general
      pharmacophores and make comparisons among claimed compounds. On the other hand,
      the identification of multi-target compounds seems a reliable goal. Thus, it is
      reasonable that quinazoline compounds will be studied and developed for multi
      target therapies.

PMID- 22404098
TI  - Novel application of four-dimensional sonography with B-flow imaging and
      spatiotemporal image correlation in the assessment of fetal congenital heart
      defects.
AB  - AIMS: To evaluate the role of four-dimensional (4D) ultrasound with B-flow
      imaging and spatiotemporal image correlation (STIC) in the evaluation of normal
      fetal heart and congenital heart disease during pregnancy. METHODS: Volume data
      sets of the fetal heart were acquired with automated transverse and longitudinal
      sweeps of the anterior chest wall. We studied 31 normal fetuses and 28 fetuses
      with congenital heart disease (6 with double-outlet right ventricle, 5 with
      complete transposition of great arteries, 8 with tetralogy of Fallot, 3 with
      right aortic arch, 2 with persistent left superior vena cava, 3 with truncus
      arteriosus communis, and 1 with interruption of aortic arch) at gestation ages
      ranging from 18 to 39 weeks using transabdominal 4D B-flow sonography with STIC
      (4D BF-STIC). RESULTS: Four-dimensional BF-STIC demonstrated dynamic angiographic
      features in both normal and abnormal fetal hearts. Four-dimensional BF-STIC
      images could not be obtained in two normal fetuses at 18.9 and 35.6 weeks because
      of the high fetal heart rate and inappropriate fetal position. Of the other 29
      fetuses all extracardiac vessels such as aorta, pulmonary artery, ductus
      arteriosus, inferior vena cava, and ductus venosus could be detected on
      reconstructed images. In seven normal cases, a 4D image was recorded to allow
      simultaneous visualization of all four pulmonary veins. In the 28 fetuses with
      cardiac anomalies, 4D sonography with B-flow imaging and STIC detected the
      "digital casts" of the outflow tracts, great arteries, and veins draining into
      the heart. These results demonstrate spatial relationship among these structures
      which provide important anatomical information. CONCLUSION: Four-dimensional BF
      STIC provides a means of real time three-dimensional evaluation of fetal
      extracardiac hemodynamics in the second and third trimesters. This novel
      technique assists in the evaluation of fetal cardiac hemodynamics and may play an
      important role in future fetal cardiac research and in the identification of
      anatomical features of different congenital cardiac anomalies.

PMID- 22404099
TI  - Functional variable number of tandem repeats variation in the promoter of proto
      oncogene PTTG1IP is associated with risk of estrogen receptor-positive breast
      cancer.
AB  - Genetic polymorphisms in the signalling pathway of estrogen receptor (ER) could
      modify the risk of breast cancer. A variable number of tandem repeats (VNTR)
      polymorphism in the promoter of PTTG1IP, pituitary tumor transforming gene
      binding factor targeted by estrogen receptor alpha (ERalpha) in endocrine
      neoplasia, has been shown to be functional, but its relevance to cancer etiology
      was unknown. We investigated its association with breast cancer risk by
      genotyping in 658 patients and 866 controls and further analysed its differential
      interaction with ERalpha. We found nine types of alleles ranging from 2 to 9 and
      11 repeats that form 29 distinct genotypes and 11 different biallelic repeat
      numbers. Subjects who carry the six-repeats allele (odds ratio [OR], 1.45; 95%
      confidence interval [CI], 1.17-1.79), long alleles (>=6 repeats) (OR, 1.55; 95%
      CI, 1.17-2.05) or a high dose of biallelic repeats (OR, 1.38; 95% CI, 1.07-1.77)
      were at significantly increased risk of cancer. In stratification analysis, these
      associations consistently manifested in ER-positive breast cancer: in ER
      positive, PR-positive subtype, genotypes with the six-repeats allele (OR, 1.42;
      95% CI, 1.06-1.90), long alleles (OR, 1.77; 95% CI, 1.17-2.67) or a high dose of
      biallelic repeats (OR, 1.67; 95% CI, 1.19-2.33) were associated with cancer risk;
      in ER positive, HER2-negative subtype, they were susceptible factors with the ORs
      being 1.46 (95% CI, 1.06-2.02), 2.06 (95% CI, 1.28-3.32) and 1.85 (95% CI, 1.26
      2.71), respectively. Furthermore, functional analysis revealed that an increase
      in the number of tandem repeats enhances the binding affinity of ERalpha. The
      present study provides the first epidemiological evidence that functional
      regulatory variants of PTTG1IP were associated with the risk of ER-positive
      breast cancer, further supporting its relevance as one proto-oncogene in breast
      cancer.

PMID- 22404101
TI  - Genetic polymorphisms in the estrogen receptor-alpha gene and the risk of
      endometrial cancer: a meta-analysis.
AB  - Estrogen receptor-alpha is a key mediator of the estrogen response in endometrial
      tissue. The most-studied gene variants are the PvuII and XbaI polymorphisms,
      which may be associated with altered sensitivity to estrogen. However, studies
      evaluating the associations between these polymorphisms and endometrial cancer
      risk have produced controversial conclusions. To explore a more robust estimate
      of the role of estrogen receptor-alpha polymorphisms in endometrial
      carcinogenesis, we searched all published articles indexed in PubMed, Web of
      Science, EBSCO, Highwire and the CNKI database from 1995 to 2010. Data were
      independently extracted by two reviewers using a standardized data extraction
      form. Overall, the meta-analysis included 1944 cases and 3075 controls for PvuII
      polymorphisms, and 1831 cases and 2875 controls for XbaI polymorphisms. Our
      results did not show any statistically significant association between
      endometrial cancer risk and either PvuII or XbaI polymorphisms. However, PvuII
      polymorphisms, both the CT and the CC genotypes, significantly increased the risk
      of endometrial cancer in an Asian-Australian population (pooled OR = 1.50, 95%CI
      1.09-2.08 and pooled OR = 1.55, 95%CI 1.08-2.22, respectively). The CC genotype
      significantly decreased the risk of endometrial cancer (pooled odds ratio 0.77,
      95% confidence interval 0.64-0.94) in a European population. In contrast, the
      stratified analysis suggested that the XbaI polymorphism was not significantly
      associated with endometrial cancer between different populations. This meta
      analysis provides evidence that PvuII polymorphisms in the ESR1 gene, which
      encodes for estrogen receptor-alpha, could modify the susceptibility to
      endometrial cancer. However, the genetic effect varied between different
      geographical regions for unknown reasons.

PMID- 22404100
TI  - Survival and neurodevelopmental outcome of ELBW children at 5 years of age:
      comparison of two cohorts born 10 years apart.
AB  - AIM: To examine survival and outcome of extremely low-birth-weight (ELBW)
      children (birth weight < 1000 g) in two 5-year periods, 10 years apart. METHODS:
      In a retrospective population-based study, information on all ELBW children born
      in Iceland in 1991-1995 and in 2001-2005 was obtained from the National Birth
      Registry, hospital charts and medical records. The two periods were compared.
      RESULTS: In 1991-1995, 102 of 22.261 newborn children (0.5%) were extremely low
      birth weight compared with 70 of 20.923 newborns (0.33%) in 2001-2005 (p = 0.04).
      At 5 years of age, 52% (35/67) of live-born children born in 1991-1995 were alive
      compared with 63% (31/49) of children born in 2001 - 2005 (p = 0.2). Six ELBW
      children (17%) born 1991-1995 were diagnosed with disabilities at 5 years of age,
      three with major neurodevelopmental disabilities compared with six (19%) born
      2001-2005, thereof one with severe neurodevelopmental disabilities (p = 0.57).
      CONCLUSION: The incidence of childhood disabilities in ELBW children in Iceland
      remains stable despite an increase in survival rate. The severity of
      neurodevelopmental disabilities has decreased.

PMID- 22404102
TI  - A mathematical model for decreasing the surface area of surgical excisions.
AB  - BACKGROUND: Repair of lower extremity excision defects poses a surgical
      challenge, and as a result, split-thickness skin grafting is often used to close
      large defects. By minimizing the size of the defect, a smaller graft can be used,
      which may translate into improvements in wound healing and the aesthetic outcome.
      OBJECTIVE: To demonstrate, using a mathematical model, how to decrease the
      surface area of excisions on lower extremities requiring split-thickness skin
      grafting. METHODS: Four patients had cutaneous neoplasms excised from their lower
      legs. The resulting defects underwent partial primary closure with removal of
      Burrow's triangle. The new dimensions of the defect were recorded, and the
      surface area of the pre- and postprimary closure was calculated. RESULTS: Modest
      decreases in the dimensions of the ovoid-ellipsoid defect translated to large
      decreases in the surface area requiring split-thickness skin graft repair.
      CONCLUSION: Using a mathematical model, we quantified how it is possible to
      decrease the size of an excision site. This reduction in surface area may
      translate to benefits in a postoperative outcomes.

PMID- 22404103
TI  - Re-evaluation of the risk for major adverse cardiovascular events in patients
      treated with anti-IL-12/23 biological agents for chronic plaque psoriasis: a meta
      analysis of randomized controlled trials.
AB  - OBJECTIVE: To detect a detrimental or beneficial effect of anti-IL-12/23
      biological agents (ustekinumab and briakinumab) for the treatment of chronic
      plaque psoriasis on major adverse cardiovascular events (MACEs). DESIGN:
      Systematic review and meta-analysis MEDLINE, EMBASE, the Cochrane Skin Group
      Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) in
      The Cochrane Library, SciVerse Scopus and ongoing trial registries were searched
      from inception until December 2011. Search strategy, eligibility criteria, data
      and statistical analysis methods were defined prior to the literature search.
      Randomized, placebo-controlled, double-blind, monotherapy studies with safety
      data for MACEs of IL-12/23 antibodies in adults were eligible for inclusion.
      Studies of psoriatic arthritis were excluded. Information from each study was
      extracted independently by two reviewers, using a standardized data extraction
      form. The primary outcome measure was the number of MACEs during the placebo
      controlled phase of treatment. RESULTS: MACEs include myocardial infarction,
      cerebrovascular accident or cardiovascular death. No statistical heterogeneity
      across the studies using the I(2) statistic (I(2) = 0) was found. We employed
      Peto one-step method to determine odds ratios and quantify a possible detrimental
      or beneficial association of IL-12/23 antibodies treatment with MACEs. We found a
      possible higher risk of MACEs in those patients treated with IL-12/23 antibodies
      compared with those at placebo (OR = 4.23, 95% CI: 1.07-16.75, P = 0.04). This
      study is unaffected by non-reporting of outcomes with no events. CONCLUSION:
      Compared with placebo, there was a significant difference in the rate of MACEs
      observed in patients receiving anti-IL-12/23 biological agents.

PMID- 22404104
TI  - Calculation of magnetic couplings in hydrogen-bonded Cu(II) complexes using
      density functional theory.
AB  - The performance of recent density functionals for computation of molecular
      magnetic coupling constants (J) in hydrogen-bonded systems is evaluated. A survey
      of six Cu(II) dinuclear complexes is considered. The global accuracy trend is
      GGAs <InvalidTag-GGAs < hybrid-GGAs ~ hybrid meta-GGAs. Hybrid meta-GGAs do not
      generally provide any improvement over well-established hybrid functionals such
      as B3LYP. It is also seen that spin projection values agree best with experiment
      if one uses functionals that either have large quantities of exact exchange such
      as B2PLYP or functionals with long-range Coulomb screening such as CAM-B3LYP or
      LC-omegaPBE, thus suggesting that these provide a description that is free from
      self-interaction errors.

PMID- 22404105
TI  - Institutionalization of brief alcohol intervention in primary health care-the
      Finnish case.
AB  - BACKGROUND: There have been several research and practical projects to promote
      alcohol brief interventions (BIs) in healthcare settings, but no reports of
      nationwide outcome have so far been published. In Finland, these activities
      started in the early 1990s, and in the past years, the focus has been mainly on
      primary and occupational health care. The aim of the present study was to
      ascertain whether the extensive and long-lasting implementation efforts have led
      to the institutionalization of this activity among primary healthcare physicians
      and to the identification of factors that may be associated with it. METHODS: The
      data were gathered by a questionnaire sent to all Finnish primary healthcare
      physicians in 2002 and 2007. In both years, the questionnaire contained questions
      on demographics, professional background and the physicians' own BI activity
      (regular, occasional, or none). In 2007, a question eliciting information about
      the change in BI activity during the past 5 years was added. The response rate
      was 67.1% (95% CI 65.4 to 68.8) (2,001/2,980) in 2002 and 50.9% (95% CI 49.2 to
      52.6) (1,610/3,163) in 2007. RESULTS: The number of physicians offering BI had
      increased during the study years from 59.2 to 78.5%. Regular activity was
      reported in 2002 by 9.3% of physicians and in 2007 by 17.2% and occasional
      activity correspondingly by 49.9 and 61.3%. Of the physicians who offered BI in
      2007, 52.4% reported increased activity and 42.6% similar activity to that
      reported 5 years earlier. Having a specialist's license in general practice or
      occupational health care or long experience as a primary healthcare physician
      predicted high activity. CONCLUSIONS: The BI activity of Finnish primary
      healthcare physicians is reasonably high and rising. Training and motivating
      those with low BI activity remains future challenge.

PMID- 22404106
TI  - Correlation of TSH with the risk of paediatric thyroid carcinoma.
AB  - OBJECTIVE: Risk factors for the rare and unique entity of paediatric thyroid
      cancer are becoming more clearly defined. This study investigated the association
      of thyroid-stimulating hormone (TSH) with the diagnosis of differentiated thyroid
      carcinoma in the paediatric population. No previous studies have correlated the
      paediatric thyroid cancer risk with TSH levels. DESIGN: Retrospective case
      controlled study. PATIENTS: A total of 116 paediatric patients with an indication
      for thyroidectomy referred to Seattle Children's Hospital, a major paediatric
      tertiary medical centre, between January 1997 and January 2011 were assessed.
      Excluding confounders that would directly affect TSH values, 78 patients (29
      patients with and 49 patients without thyroid cancer) between the ages of 3 and
      20 years were evaluated. MEASUREMENTS: Preoperative TSH values correlated with
      pathology review of en bloc resected thyroid tissue specimens. RESULTS: The
      diagnosis of paediatric thyroid carcinoma was significantly associated with
      elevated TSH levels. The average TSH level (2.32 +/- 0.51 mIU/l) was
      significantly greater than the TSH level (1.08 +/- 0.14 mIU/l) noted in patients
      without malignancy (P = 0.03). A rightward skew of TSH was associated with
      paediatric patients harbouring paediatric thyroid carcinoma, with a TSH level
      >=2.50 mIU/l correlating with a significantly increased odds ratio of thyroid
      cancer (OR 8.05, 95% CI 1.41-81.39, P = 0.0073) relative to a normal TSH range of
      0.40-2.49 mIU/l. CONCLUSIONS: Paediatric thyroid carcinoma is associated with TSH
      level >= 2.50 mIU/l, which may be useful to identify a higher risk of malignancy
      in a paediatric patient with a thyroid nodule.

PMID- 22404107
TI  - Aldehyde oxidase functions as a superoxide generating NADH oxidase: an important
      redox regulated pathway of cellular oxygen radical formation.
AB  - The enzyme aldehyde oxidase (AO) is a member of the molybdenum hydroxylase family
      that includes xanthine oxidoreductase (XOR); however, its physiological
      substrates and functions remain unclear. Moreover, little is known about its role
      in cellular redox stress. Utilizing electron paramagnetic resonance spin
      trapping, we measured the role of AO in the generation of reactive oxygen species
      (ROS) through the oxidation of NADH and the effects of inhibitors of AO on NADH
      mediated superoxide (O(2)(*-)) generation. NADH was found to be a good substrate
      for AO with apparent K(m) and V(max) values of 29 MUM and 12 nmol min(-1) mg(-1),
      respectively. From O(2)(*-) generation measurements by cytochrome c reduction the
      apparent K(m) and V(max) values of NADH for AO were 11 MUM and 15 nmol min(-1)
      mg(-1), respectively. With NADH oxidation by AO, >=65% of the total electron flux
      led to O(2)(*-) generation. Diphenyleneiodonium completely inhibited AO-mediated
      O(2)(*-) production, confirming that this occurs at the FAD site. Inhibitors of
      this NADH-derived O(2)(*-) generation were studied with amidone the most potent
      exerting complete inhibition at 100 MUM concentration, while 150 MUM menadione,
      raloxifene, or beta-estradiol led to 81%, 46%, or 26% inhibition, respectively.
      From the kinetic data, and the levels of AO and NADH, O(2)(*-) production was
      estimated to be ~89 and ~4 nM/s in liver and heart, respectively, much higher
      than that estimated for XOR under similar conditions. Owing to the ubiquitous
      distribution of NADH, aldehydes, and other endogenous AO substrates, AO is
      predicted to have an important role in cellular redox stress and related disease
      pathogenesis.

PMID- 22404108
TI  - New antibacterials for the treatment of toxoplasmosis; a patent review.
AB  - INTRODUCTION: Toxoplasma gondii is an opportunistic protozoan parasite
      responsible for toxoplasmosis. T. gondii is able to infect a wide range of hosts,
      particularly humans and warm-blooded animals. Toxoplasmosis can be considered as
      one of the most prevalent parasitic diseases affecting close to one billion
      people worldwide, but its current chemotherapy is still deficient and is only
      effective in the acute phase of the disease. AREAS COVERED: This review covers
      different approaches to toxoplasmosis chemotherapy focused on the metabolic
      differences between the host and the parasite. Selective action on different
      targets such as the isoprenoid pathway, dihydrofolate reductase, T. gondii
      adenosine kinase, different antibacterials, T. gondii histone deacetylase and
      calcium-dependent protein kinases is discussed. EXPERT OPINION: A new and safe
      chemotherapy is needed, as T. gondii causes serious morbidity and mortality in
      pregnant women and immunodeficient patients undergoing chemotherapy. A particular
      drawback of the available treatments is the lack of efficacy against the tissue
      cyst of the parasite. During this review a broad scope of several attractive
      targets for drug design have been presented. In this context, the isoprenoid
      pathway, dihydrofolate reductase, T. gondii histone deacetylase are promising
      molecular targets.

PMID- 22404109
TI  - Arabidopsis thaliana histone deacetylase 14 (HDA14) is an alpha-tubulin
      deacetylase that associates with PP2A and enriches in the microtubule fraction
      with the putative histone acetyltransferase ELP3.
AB  - It is now emerging that many proteins are regulated by a variety of covalent
      modifications. Using microcystin-affinity chromatography we have purified
      multiple protein phosphatases and their associated proteins from Arabidopsis
      thaliana. One major protein purified was the histone deacetylase HDA14. We
      demonstrate that HDA14 can deacetylate alpha-tubulin, associates with alpha/beta
      tubulin and is retained on GTP/taxol-stabilized microtubules, at least in part,
      by direct association with the PP2A-A2 subunit. Like HDA14, the putative histone
      acetyltransferase ELP3 was purified on microcystin-Sepharose and is also enriched
      at microtubules, potentially functioning in opposition to HDA14 as the alpha
      tubulin acetylating enzyme. Consistent with the likelihood of it having many
      substrates throughout the cell, we demonstrate that HDA14, ELP3 and the PP2A A
      subunits A1, A2 and A3 all reside in both the nucleus and cytosol of the cell.
      The association of a histone deacetylase with PP2A suggests a direct link between
      protein phosphorylation and acetylation.

PMID- 22404110
TI  - Limited geographic distribution of certain strains of the bioluminescent symbiont
      Photobacterium leiognathi.
AB  - Photobacterium leiognathi is a facultative bioluminescent symbiont of marine
      animals. Strains of P. leiognathi that are merodiploid for the luminescence genes
      (lux-rib operon) have been previously obtained only from Japan. In contrast,
      strains bearing a single lux-rib operon have been obtained from all the areas
      sampled in Japan and the western Pacific. In this study, we tested whether
      distribution of merodiploid P. leiognathi is limited by physical barriers in the
      environment, or because fish in the western Pacific preferentially form symbiosis
      with bacteria bearing a single lux-rib operon. We collected light organ symbionts
      from Secutor indicius, a fish species that is typically found in the western
      Pacific and has only recently expanded its geographic range to Japan. We found
      that all S. indicius specimens collected from Japan formed symbiosis only with
      single lux-rib operon-bearing strains, although fish from other species collected
      from the same geographic area frequently contained merodiploid strains. This
      result shows that S. indicius were preferentially colonized by bacteria bearing a
      single lux-rib operon and suggests that the limited geographic distribution of
      merodiploid P. leiognathi can be attributed to preferential colonization of fish
      species found in the western Pacific by strains bearing only a single lux-rib
      operon.

PMID- 22404111
TI  - Surface modifications of microprojection arrays for improved biomarker capture in
      the skin of live mice.
AB  - New technologies are needed to translate biomarker discovery research into
      simple, inexpensive, and effective molecular diagnostic assays for use by
      clinicians or patients to guide and monitor treatment. Microprojection arrays
      were recently introduced as tools which, when applied to the skin, penetrate into
      the dermal tissue, and capture specific circulating biomarkers. In our initial
      work on Microprojection arrays, carbodiimide chemistry was used to immobilize
      biomarker-specific probes for affinity capture in vivo using a mouse model.
      However, as the observed capture efficiencies were relatively low, with
      significant variation across the surface, here we investigated the surface
      modifications to (a) determine the source of the variability and (b) find ways of
      improving capture efficiency. We found the protein immobilization step accounted
      for almost all of the variability in surface uniformity. Varying the protein
      immobilization conditions following a standard carbodiimide activation process
      resulted in a reduction in overall variation 14-fold and an increase in captured
      biomarker amount ~18-fold. In conclusion, we found that investigating and
      optimizing the surface chemistry of microprojection array devices led to drastic
      improvements in capturing biomarkers from skin fluid.

PMID- 22404112
TI  - Personality effects on cardiovascular reactivity: need for closure moderates the
      impact of task difficulty on engagement-related myocardial beta-adrenergic
      activity.
AB  - An experiment assessed the joint effect of dispositional need for closure (NFC)
      and task difficulty on engagement-related myocardial beta-adrenergic activity.
      Participants who scored either low or high on the NFC scale performed an
      ambiguous categorization task with either low or high difficulty. Confirming the
      theory-derived predictions, task difficulty effects on pre-ejection period (PEP)
      reactivity were moderated by NFC. If difficulty was low, PEP reactivity was low
      and independent of the participants' NFC level. If difficulty was high,
      participants with high NFC showed increased PEP reactivity compared to
      participants with low NFC. These results extend previous research on Wright's
      model of engagement-related cardiovascular reactivity and suggest that the model
      may provide a useful framework for assessing the impact of personality on
      cardiovascular response.

PMID- 22404113
TI  - Analyzing the responses of saccharin in context with melatonin receptors on the
      melanophores of the fish Labeo rohita (Ham.).
AB  - The hormone melatonin regulates the biological clock and assist in various other
      physiologies of vertebrates. Present work is intended to check the affinity of
      saccharin towards the melatonin receptors and the possible role of saccharin
      interference in the melatonin physiology. The present in vitro study is based on
      the working model of isolated scale melanophores in the dorso-lateral region of
      Labeo rohita. The pigment cells were incubated in the agonist and the antagonists
      within a limited time frame and subsequently their Melanophore Size Index (MSI)
      were calculated. The inferences were drafted through the observed signal
      transduction upshots in pigment translocations within the melanophores.
      Saccharin, in a wide dose range, has consistently induced a concentration-related
      aggregation similar to the aggregatory effect as shown by melatonin on the
      melanophores. Binding of saccharin with the receptors and eliciting its
      aggregatory effect is partially dependent on the release of neurotransmitters.
      The aggregatory effects were found to be significantly blocked by luzindole,
      K185, and prazosin, which are the potent melatonin receptor blockers, at the
      higher concentrations of saccharin. Hence, all the three subtypes of melatonin
      receptors viz. MT1, MT2, and MT3 are participating in saccharin-mediated
      aggregations. Blocking by neomycin shows that Ca2+ ions are very crucial in
      dispensing the aggregatory effect of the sweetener. This research demands that an
      intensive and careful thorough study should be made about saccharin, specifically
      its effects upon melatonin physiology, before its unwarranted use as the food
      ingredients for human use.

PMID- 22404114
TI  - Light levels of anaesthesia after relaxation for tracheal intubation - comparison
      of succinylcholine and cis-atracurium.
AB  - BACKGROUND: Use of a single bolus of a hypnotic together with non-depolarizing
      muscle relaxants for anaesthesia induction may cause inappropriate light levels
      of anaesthesia (ILLA). The purpose of this study was to compare the incidence of
      ILLA during anaesthesia induction using either cis-atracurium (CIS) or
      succinylcholine (SUC). METHODS: Patients (n = 65) received fentanyl and propofol.
      Relaxants were randomly chosen and were either CIS 0.15 mg/kg, or SUC 1 mg/kg.
      After achieving relaxation, ILLA were assessed double-blinded by the isolated
      forearm technique and electroencephalogram -derived values. RESULTS: Time from
      induction to complete relaxation was 335 +/- 55 s with CIS and 141 +/- 26 s with
      SUC. Nine patients in the CIS group (26%), but no patient in the SUC group
      responded to commands before endotracheal intubation (P < 0.01). During the
      entire induction up to 1 min after intubation in the CIS group, 24 of 35 patients
      (68%) showed 31 episodes of ILLA, as defined as responsiveness to commands and
      spontaneous movements. With SUC, 8 of 30 patients (27%) showed 11 episodes of
      ILLA (P < 0.01). In patients with ILLA, state entropy (SE) and spectral edge
      frequency (SEF) were 68 +/- 10 (mean +/- standard deviation) and 17 +/- 4 Hz,
      respectively, and in patients without ILLA, SE and SEF were 40 +/- 14 and 12 +/-
      3 Hz, respectively (P < 0.01). CONCLUSION: The onset time of a muscle relaxant
      has substantial impact on the incidence of ILLA during induction of anaesthesia.
      Entropy and SEF may indicate the presence of ILLA.

PMID- 22404115
TI  - Seroprevalence of hepatitis E virus infection in rural and urban populations,
      Tunisia.
AB  - Hepatitis E virus (HEV) is one of the leading agents of acute hepatitis. This
      study investigated the prevalence and risk factors of HEV infection in the
      Tunisian adult general population, either in blood donors (n=687) or in patients
      hospitalized for acute hepatitis (n=202). The mode of transmission differed
      between these two populations: contact with animals and living in a rural habitat
      were the main risk factors for being in contact with HEV in asymptomatic blood
      donors, while HEV was contracted through contaminated water in symptomatic cases.
      HEV seroprevalence in adult blood donors in Tunisia was relatively low (5.4%) and
      increased with age.

PMID- 22404116
TI  - Inhibitory effect and mechanisms of an anthocyanins- and anthocyanidins-rich
      extract from purple-shoot tea on colorectal carcinoma cell proliferation.
AB  - One newly bred variety of tea cultivar, purple-shoot tea, was selected to
      evaluate its antiproliferative effects on colorectal carcinoma cells, as well as
      normal colon cells. The phytochemicals and identified catechins of purple-shoot
      tea extract (PTE) were significantly higher than that of ordinary tea, especially
      the anthocyanins (surpassed by 135-fold) and anthocyanidins (surpassed by 3.5
      fold). PTE inhibited the proliferation of COLO 320DM (IC(50) = 64.9 MUg/mL) and
      HT-29 (IC(50) = 55.2 MUg/mL) by blocking cell cycle progression during the
      G(0)/G(1) phase and inducing apoptotic death. Western blotting indicated that PTE
      induced cell cycle arrest by reducing the expression of cyclin E and cyclin D1 in
      COLO 320DM and the upregulation of p21 and p27 cyclin-dependent kinase inhibitors
      in HT-29. Two cells treated with PTE also indicated the cleavage of PARP,
      activation of caspase 3, and an increased Bax/Bcl-2 ratio. Our results showed
      that PTE is a potential novel dietary agent for colorectal cancer
      chemoprevention.

PMID- 22404117
TI  - Resolvins: anti-inflammatory and proresolving mediators derived from omega-3
      polyunsaturated fatty acids.
AB  - Omega-3 polyunsaturated fatty acids (PUFAs) are essential to health, and
      deficiencies in these PUFAs are linked to chronic disease. Although important
      insights into the diverse biological roles of PUFAs have been made, the
      mechanistic basis underlying their protective actions is still emerging. Studies
      over the past decade have elucidated that omega-3 PUFAs are enzymatically
      converted into bioactive autacoids that have inflammation-resolving properties.
      Among these, resolvins have emerged as an important family that has potent and
      stereospecific immunomodulatory roles, elucidation of which has contributed to a
      growing body of literature demonstrating that resolution of acute inflammation is
      an active process. In addition to their direct interactions with immune cells,
      resolvins have effects on nonimmune cells as well, suggesting a much broader role
      in biological systems than originally appreciated. In this review, we describe
      the endogenous biosynthesis and immunomodulatory actions of resolvins and
      highlight their emerging roles in health and disease.

PMID- 22404119
TI  - Hypomagnesemia and inflammation: clinical and basic aspects.
AB  - In recent years, increasing awareness of hypomagnesemia has resulted in clinical
      trials that associate this mineral deficiency with diabetes, metabolic syndrome,
      and drug therapies for cancer and cardiovascular diseases. However, diagnostic
      testing for tissue deficiency of magnesium still presents a challenge.
      Investigations of animal and cellular responses to magnesium deficiency have
      found evidence of complex proinflammatory pathways that may lead to greater
      understanding of mediators of the pathobiology in neuronal, cardiovascular,
      intestinal, renal, and hematological tissues. The roles of free radicals,
      cytokines, neuropeptides, endotoxin, endogenous antioxidants, and vascular
      permeability, and interventions to limit the inflammatory response associated
      with these parameters, are outlined in basic studies of magnesium deficiency. It
      is hoped that this limited review of inflammation associated with some diseases
      complicated by magnesium deficiency will prompt greater awareness by clinicians
      and other health providers and in turn increase efforts to prevent and treat this
      disorder.

PMID- 22404120
TI  - Selenoproteins and cancer prevention.
AB  - The discovery of multiple selenoproteins has raised tantalizing questions about
      their role in maintaining normal cellular function. Unfortunately, many of these
      remain inadequately investigated. While they have a role in maintaining redox
      balance, other functions are becoming increasingly recognized. As the roles of
      these selenoproteins are further characterized, a better understanding of the
      true physiological significance of this trace element will arise. This knowledge
      will be essential in defining optimum intakes to achieve cellular homeostasis in
      order to optimize health, including a reduction in cancer, for diverse
      populations. Human variation in the response to selenium likely reflects
      significant interactions between the type and amounts of selenium consumed with
      the genome and a host of environmental factors including the totality of the
      diet, as discussed in this review.

PMID- 22404121
TI  - An unexpected life in nutrition.
AB  - In this biographical article, I describe the evolution of my career in nutrition
      from an early period as an animal nutritionist interested in amino acid
      metabolism and genetic variation in nutrient requirements to an involvement in
      human nutrition and international public health. The career changes were in some
      respects a mirror of the evolution of nutritional science in my lifetime. I spent
      my entire career at Cornell University in what I think of as three distinct
      phases. As a researcher and teacher in the Poultry Science Department, I was able
      to do research in animal nutrition and witness the rapid industrialization of the
      production of poultry meat and eggs, helped by the findings of the era of
      nutrient discovery in nutritional science. Later I had the opportunity to lead
      the reorganization of human nutrition at Cornell during a period when research in
      nutritional science turned away from identifying new nutrients and became
      increasingly concerned with the roles of diet and chronic disease. During this
      period my research focus evolved as I became interested in aspects of
      international nutrition problems, particularly the influence of parasitic
      infections on child health and nutrition. I also became involved nationally in
      nutrition issues through participation in organizations such as the National
      Nutrition Consortium, the Food and Nutrition Board, and National Institutes of
      Health study sections at a time of great ferment in nutrition about the
      relationship of dietary patterns to health. Finally, I became provost of Cornell
      University and involved in the administration of a major research university. I
      describe my career in the context of my origins and early education springing
      from life on a sustainable family farm in rural Illinois.

PMID- 22404118
TI  - Mechanisms of inflammatory responses in obese adipose tissue.
AB  - The fields of immunology and metabolism are rapidly converging on adipose tissue.
      During obesity, many immune cells infiltrate or populate in adipose tissue and
      promote a low-grade chronic inflammation. Studies to date have suggested that
      perturbation of inflammation is critically linked to nutrient metabolic pathways
      and to obesity-associated complications such as insulin resistance and type 2
      diabetes. Despite these advances, however, many open questions remain including
      how inflammatory responses are initiated and maintained, how nutrients impact the
      function of various immune populations, and how inflammatory responses affect
      systemic insulin sensitivity. Here we review recent studies on the roles of
      various immune cells at different phases of obesity and discuss molecular
      mechanisms underlying obesity-associated inflammation. Better understanding of
      the events occurring in adipose tissue will provide insights into the
      pathophysiological role of inflammation in obesity and shed light on the
      pathogenesis of obesity-associated metabolic syndrome.

PMID- 22404122
TI  - Self-injurious behaviour in individuals with autism spectrum disorder and
      intellectual disability.
AB  - BACKGROUND: Autism spectrum disorder (ASD) has been identified as a risk marker
      for self-injurious behaviour. In this study we aimed to describe the prevalence,
      topography and correlates of self-injury in individuals with ASD in contrast to
      individuals with Fragile X and Down syndromes and examine person characteristics
      associated with self-injury across and within these groups. METHOD: Carers of
      individuals with ASD (n = 149; mean age = 9.98, SD = 4.86), Fragile X syndrome (n
      = 123; mean age = 15.32, SD = 8.74) and Down syndrome (n = 49; mean age = 15.84,
      SD = 12.59) completed questionnaires relating to the presence and topography of
      self-injury. Information was also gathered regarding demographic characteristics,
      affect, autistic behaviour, hyperactivity, impulsivity and repetitive behaviour.
      RESULTS: Self-injurious behaviour was displayed by 50% of the ASD sample: a
      significantly higher prevalence than in the Down syndrome group (18.4%) but
      broadly similar to the prevalence in Fragile X syndrome (54.5%). Self-injury was
      associated with significantly higher levels of autistic behaviour within the Down
      and Fragile X syndrome groups. Within the ASD group, the presence of self-injury
      was associated with significantly higher levels of impulsivity and hyperactivity,
      negative affect and significantly lower levels of ability and speech.
      CONCLUSIONS: Self-injurious behaviour is prevalent in individuals with ASD and
      the presence of ASD phenomenology increases the risk of self-injury in
      individuals with known genetic disorders but without a diagnosis of idiopathic
      autism. Person characteristics associated with self-injury in ASD indicate a role
      for impaired behavioural inhibition, low levels of ability and negative affect in
      the development of self-injurious behaviour.

PMID- 22404123
TI  - Why should American headache and migraine patients still be treated with
      butalbital-containing medicine?

PMID- 22404124
TI  - Chronic pulmonary hypertension causes significant interventricular spatiotemporal
      dyssynchrony when onset of diastolic flow signals are assessed by color m-mode.
AB  - BACKGROUND: Color M-mode (CMM) has been useful in characterizing left ventricular
      (LV) relaxation as well as providing information regarding right ventricular (RV)
      filling dynamics and pressure gradients. The spatiotemporal resolution of CMM
      offers a unique opportunity to study the effect of chronic pulmonary hypertension
      (cPH) on biventricular diastolic function. METHODS: Propagation velocities of LV
      and RV diastolic flows were obtained from 20 individuals with normal pulmonary
      artery systolic pressures, designated Group I (mean age 50 +/- 12 years and 32 +/
      6 mmHg) and from 30 patients with cPH, designated Group II (mean age 55 +/- 14
      years and 81 +/- 25 mmHg). RESULTS: Group II patients not only had a significant
      difference between RV and LV onset of early (13 +/- 55 vs. -223 +/- 333 msec; P <
      0.003) and late (-494 +/- 467 vs. -125 +/- 258 msec; P < 0.001) diastolic flows;
      but also had lower propagation velocities of the main RV (40 +/- 10 vs. 28 +/- 10
      cm/sec; P < 0.0001) and LV (52 +/- 11 vs. 37 +/- 15 cm/sec; P < 0.0003) diastolic
      flows than Group I individuals. CONCLUSIONS: It appears that cPH disrupts not
      only RV and LV diastolic signal distribution but also their temporal occurrence
      as well as reducing the propagation velocities of the main diastolic signals in
      both ventricles. These results seem to imply that cPH causes significant
      interventricular diastolic dyssynchrony and further studies are now needed to
      correlate these findings with regard to symptoms and patient clinical outcomes.

PMID- 22404125
TI  - High levels of DJ-1 protein in nipple fluid of patients with breast cancer.
AB  - As we have previously demonstrated that some breast cancer cell lines secrete DJ
      1 protein, we examined here whether breast cancer cells secrete DJ-1 protein in
      vivo. To this end, the levels of DJ-1 protein present in 136 specimens of nipple
      fluid was examined by enzyme-linked immunosorbent assay (ELISA). The average
      concentration of DJ-1 protein detected in diluted samples from 47 patients with
      invasive ductal carcinoma (IDC) was 22.4 ng/mL, while it was 18.6 ng/mL in 26
      patients with ductal carcinoma in situ (DCIS). In contrast, the average DJ-1
      concentration in samples from 63 women with benign lesions was 2.7 ng/mL,
      demonstrating that higher DJ-1 protein levels were detected in nipple fluid in
      the presence of cancer cells than in the presence of benign lesions (P < 0.0001).
      When a cut-off level of 3.0 ng/mL was applied, the higher level of DJ-1 was shown
      to be of significant clinical value for predicting the presence of breast cancer
      (85.9% specificity, 75% sensitivity; P < 0.0001). Multivariate logistic analysis
      that included established factors such as nipple discharge cytology, ductoscopic
      cytology, and carcinoembryonic antigen level further showed that the level of DJ
      1 protein alone is of significant value for predicting the presence of breast
      cancer. Immunohistochemistry and in situ hybridization also showed that the low
      expression of DJ-1 protein, despite high mRNA expression, was significantly
      correlated with high DJ-1 protein levels in the nipple fluid. These data indicate
      that breast cancer cells secrete DJ-1 protein in vivo, and that its level is a
      potential indicator of breast cancer in patients with nipple discharge.

PMID- 22404126
TI  - Paediatric drug use with focus on off-label prescriptions at Swedish hospitals -
      a nationwide study.
AB  - AIM: To perform a nationwide investigation of paediatric drug use at Swedish
      hospitals, including an analysis of off-label drug use. METHODS: All paediatric
      hospitals in Sweden were invited to register all prescriptions to children, aged
      between 0 and 18, during two separate 2-day-periods in 2008. Data were reported
      and analysed with respect to licence status and proportion of and reasons for off
      label drug use. RESULTS: Data on 11,294 prescriptions to 2947 paediatric patients
      were received. Drugs associated with pain relief, infection, prematurity,
      nutrition and surgery or anaesthesia were most commonly used. Paracetamol was the
      most frequently used drug on-label and also among the most commonly used off
      label drugs. Nearly half (49%) of all administered prescriptions concerned
      unlicensed drugs, off-label drugs or extemporaneously prepared drugs. The
      corresponding rate among neonates was 69%. Lack of paediatric information in the
      Summary of Product Characteristics was the main reason for off-label
      classification. CONCLUSIONS: Paediatric off-label drug use is common at Swedish
      hospitals, and nearly half of all prescriptions were not documented for use in
      children. The findings emphasize a need for paediatric clinical studies as well
      as compilation of existing clinical experience and scattered evidence,
      particularly for drug treatment in infants and neonates.

PMID- 22404127
TI  - Melanocyte antigen-specific antibodies cannot be used as markers for recent
      disease activity in patients with vitiligo.
AB  - BACKGROUND: Objective parameters to assess disease activity in non-segmental
      vitiligo are lacking. Melanocyte antigen-specific antibodies are frequently found
      in the sera of patients with vitiligo and the presence of these antibodies may
      correlate with disease activity. OBJECTIVE: To investigate the relationship
      between melanocyte antigen-specific antibodies and recent disease activity in
      patients with vitiligo and to evaluate the potential usefulness of this objective
      parameter in daily clinical practice. METHODS: The prevalence of tyrosinase,
      melanoma antigen recognized by T-cells-1 (MART1), melanin-concentrating hormone
      receptor-1 (MCHR1), gp100 and tyrosine hydroxylase (TH) antibodies was evaluated
      in 21 patients with non-segmental vitiligo and in 20 healthy controls. RESULTS:
      In 21 patients, nine (42.8%) showed antibody responses against tyrosinase, MART1,
      MCHR1, gp100 or TH. No antibody responses were found in the 20 controls. No
      correlation was found between the presence of antibodies and recent disease
      activity or other clinical characteristics such as age, gender, extension and
      duration of vitiligo. CONCLUSIONS: In this study, 42.8% of the vitiligo patients
      showed an antibody response to melanocyte antigen-specific antigens. However, the
      presence of antibodies against melanocytes did not correlate with recent disease
      activity or other relevant disease parameters, and for the moment screening for
      these antibodies in individual patients does not appear to be clinically
      relevant.

PMID- 22404128
TI  - Sexual functioning, quality of life and pelvic pain 12 months after endometriosis
      surgery including vaginal resection.
AB  - OBJECTIVE: To evaluate sexual function, quality of life and pelvic pain after
      endometriosis surgery including vaginal resection. DESIGN: Prospective
      observational study with 12 months follow up. SETTING: Regional central hospital
      and university hospital. POPULATION: Twenty-two patients with deep endometriotic
      nodules in the posterior fornix of the vagina undergoing complete excision of
      endometriosis, including vaginal resection. METHODS: Sexual functioning was
      measured with the McCoy Female Sexuality Questionnaire, quality of life with a
      generic questionnaire (15D) and pain with a 10-point visual analog scale.
      Questionnaires were completed before and 12 months after the surgery. Main
      outcome measures. Changes in sexual function scores, quality-of-life scores and
      pain. RESULTS: Twelve months after surgery, the sexual satisfaction score was
      higher (p= 0.03) and the sexual problems score lower (p= 0.04) compared with
      baseline values. Health-related quality-of-life scores for discomfort and
      symptoms (p= 0.001), distress (p= 0.04), vitality (p= 0.03) and sexual activity
      (p= 0.001), and the overall 15D score (p < 0.001), were significantly improved.
      The severity of all studied types of pain was significantly decreased (p < 0.05).
      CONCLUSIONS: Complete excision of endometriosis, including vaginal resection,
      seems to offer a significant improvement in sexual functioning, quality of life
      and pelvic pain in symptomatic patients with deeply infiltrating endometriotic
      nodules in the posterior fornix of the vagina. This surgery may be associated
      with complications and adverse new-onset symptoms, and should be performed only
      after thorough consultation with the patient.

PMID- 22404129
TI  - Periocular cutaneous malignancies: a review of the literature.
AB  - BACKGROUND: The periocular skin is susceptible to numerous benign and malignant
      neoplasms. Periocular malignancies may present differently, behave more
      aggressively, and pose greater challenges for treatment and repair than
      malignancies at other cutaneous sites. Between 5% and 10% of cutaneous
      malignancies occur periorbitally, with basal cell carcinoma reported as the most
      common malignant periocular tumor, followed by squamous cell carcinoma, sebaceous
      gland carcinoma, cutaneous melanoma, Merkel cell carcinoma, and other rare
      tumors. OBJECTIVE: To review the current literature on cutaneous malignancies of
      the periocular region pertaining to etiology, incidence, clinical presentation,
      differential diagnosis, complications, and treatment options. MATERIALS AND
      METHODS: An extensive literature review was conducted using PubMed, searching for
      articles on periocular and periorbital cutaneous malignancies. CONCLUSIONS:
      Timely diagnosis and management of periocular malignancies is essential because
      of their proximity to and potential to invade vital structures such as the orbit,
      sinuses, and brain. Surgical excision remains the standard of care for the
      majority of periorbital malignancies, but given the sensitive anatomic location,
      tissue-sparing techniques with margin control such as Mohs micrographic surgery
      are the preferred method for most nonmelanoma skin cancers. Depending on tumor
      type, other treatment modalities may include radiation, chemotherapy,
      cryosurgery, topical medications, and photodynamic therapy.

PMID- 22404130
TI  - Variation in documented care for unhealthy alcohol consumption across
      race/ethnicity in the Department of Veterans Affairs Healthcare System.
AB  - BACKGROUND: The VA Healthcare System has made progress implementing evidence
      based care for unhealthy alcohol use, but whether there are differences in care
      across race/ethnicity is unclear. We describe alcohol-related care for 3
      racial/ethnic groups among VA outpatients with unhealthy alcohol use. METHODS:
      This cross-sectional study utilized secondary quality improvement data collected
      for the VA Office of Quality and Performance (July 2006 to June 2007) to identify
      a sample of 9,194 black (n = 1,436), Hispanic (n = 500), and white (n = 7,258) VA
      outpatients who screened positive for unhealthy alcohol use (AUDIT-C score >=4
      men; >=3 women). Alcohol-related care was defined as medical record documentation
      of brief intervention (advice or feedback) and/or referral (discussion of or
      scheduled). Logistic regression models estimated the prevalence of alcohol
      related care among black, Hispanic, and white patients after adjustment for
      sociodemographic characteristics, alcohol use severity, other substance use, and
      mental health comorbidity. RESULTS: Among all eligible patients, 2,903 (32%) had
      documented alcohol-related care. Adjusted prevalences were 35.3% (95% CI 30.0 to
      40.5) for black, 27.3% (95% CI 21.1 to 33.5) for Hispanic, and 28.9% (95% CI 25.5
      to 32.3) for white patients. Differences in documented alcohol-related care
      between all racial/ethnic groups were significant (p-values all < 0.05).
      CONCLUSIONS: Among VA patients with unhealthy alcohol use, black patients had the
      highest, and Hispanic the lowest, prevalence of documented alcohol-related care.
      Future research should evaluate contextual and system-, provider-, or patient
      level factors that may attenuate racial/ethnic differences in documented alcohol
      related care, as well as whether differences in documented care are associated
      with differences in outcomes.

PMID- 22404131
TI  - Antioxidant properties of beta-carotene isomers and their role in photosystems:
      insights from Ab initio simulations.
AB  - In this work we investigate the effect of cis isomerizations and conformational
      changes on the antioxidant activity of beta-carotene, one of the most important
      pigments in nature. The electrodonating (omega(-)) and electroaccepting
      (omega(+)) powers of the most relevant isomers of beta-carotene are first
      evaluated in polar and nonpolar solvents using density functional theory (DFT),
      and these quantities are then used to establish an antioxidant scale of the
      isomers. The electrodonating power, which is directly related to the antioxidant
      activity, is shown to provide a very good correlation with the experimental data.
      Next, we compute the intermediate twisted structures of the beta-carotene isomers
      generated by partial rotation of every single bond in the polyenic chain. The
      electrodonating and electroaccepting powers are evaluated for each of these
      intermediate structures along with their maximum absorption wavelengths, which
      are computed using time-dependent DFT (TD-DFT). The trends observed for both the
      electrodonating power and the maximum absorption wavelength can be rationalized
      in terms of the effective conjugated chain length of the structure resulting from
      single bond rotations. The results obtained are used to analyze the
      conformational distribution of beta-carotene in the well-resolved photosystem I
      (PS-I) of purple cyanobacteria. It is then shown that the isomers present in this
      photosystem are those having the lowest calculated relative energies and that
      those with enhanced antioxidant activity are preferentially located in the inner
      core of the protein complex.

PMID- 22404132
TI  - Effect of pre-freezing conditions on the progressive motility recovery rate of
      human frozen spermatozoa.
AB  - We evaluated the effects of sperm concentration, progressive motility, sperm
      morphology, duration of abstinence and collection season on the progressive
      motility recovery rate of human frozen spermatozoa to identify characteristics
      that predict the progressive motility recovery rate of human frozen spermatozoa
      and improve the protocol for sperm collecting in sperm banks. A total of 14 190
      semen samples donated at Zhejiang human sperm bank of China between September
      2006 and June 2011 were collected from 1624 donors. Semen was evaluated according
      to WHO standard procedures for sperm concentration. Progressive motility, sperm
      morphology, ejaculate collection season and abstinence time were recorded. After
      freezing and thawing, the progressive motility was assessed. Results showed that
      sperm concentration, progressive motility and normal morphology were
      significantly associated with the progressive motility recovery rate of human
      frozen spermatozoa. In addition, the abstinence time and collection season also
      significantly affected progressive motility recovery rate. Our results indicated
      that sperm concentration, progressive motility and normal morphology could be
      valuable in predicting the progressive motility recovery rate of human frozen
      spermatozoa. As such, progressive motility recovery may be improved by donating
      semen when abstinent for 3-5 days and during seasons other than summer.

PMID- 22404133
TI  - Determining relative f and d orbital contributions to M-Cl covalency in MCl6(2-)
      (M = Ti, Zr, Hf, U) and UOCl5(-) using Cl K-edge X-ray absorption spectroscopy
      and time-dependent density functional theory.
AB  - Chlorine K-edge X-ray absorption spectroscopy (XAS) and ground-state and time
      dependent hybrid density functional theory (DFT) were used to probe the
      electronic structures of O(h)-MCl(6)(2-) (M = Ti, Zr, Hf, U) and C(4v)-UOCl(5)(
      ), and to determine the relative contributions of valence 3d, 4d, 5d, 6d, and 5f
      orbitals in M-Cl bonding. Spectral interpretations were guided by time-dependent
      DFT calculated transition energies and oscillator strengths, which agree well
      with the experimental XAS spectra. The data provide new spectroscopic evidence
      for the involvement of both 5f and 6d orbitals in actinide-ligand bonding in
      UCl(6)(2-). For the MCl(6)(2-), where transitions into d orbitals of t(2g)
      symmetry are spectroscopically resolved for all four complexes, the
      experimentally determined Cl 3p character per M-Cl bond increases from 8.3(4)%
      (TiCl(6)(2-)) to 10.3(5)% (ZrCl(6)(2-)), 12(1)% (HfCl(6)(2-)), and 18(1)%
      (UCl(6)(2-)). Chlorine K-edge XAS spectra of UOCl(5)(-) provide additional
      insights into the transition assignments by lowering the symmetry to C(4v), where
      five pre-edge transitions into both 5f and 6d orbitals are observed. For UCl(6)(2
      ), the XAS data suggest that orbital mixing associated with the U 5f orbitals is
      considerably lower than that of the U 6d orbitals. For both UCl(6)(2-) and
      UOCl(5)(-), the ground-state DFT calculations predict a larger 5f contribution to
      bonding than is determined experimentally. These findings are discussed in the
      context of conventional theories of covalent bonding for d- and f-block metal
      complexes.

PMID- 22404134
TI  - p21-Activated kinase inhibitors: a patent review.
AB  - INTRODUCTION: The p21-activated kinase (PAK) family of serine/threonine protein
      kinases is activated by binding to the small (p21) GTP-binding proteins Cdc42 and
      Rac. The PAK family plays important roles in cytoskeletal organisation, cellular
      morphogenesis and survival, and members of this family have been implicated in a
      wide range of diseases including cancer, infectious diseases, neurological
      disorders and arthritis. AREAS COVERED: The present review seeks to summarise
      recent (up to 2011) reports of small-molecule inhibitors of p21-activated
      kinases. Where patent applications describe activity against a broad range of
      kinases and no information was provided specifically on PAK inhibition, these are
      excluded from this review. In patents considered to be relevant, exemplary
      compounds were selected and highlighted based on their representation of the
      chemical matter claimed, potencies, structural features and subsequent disclosure
      of their properties. Selected information from non-patent literature was also
      included. EXPERT OPINION: A considerable amount of research has been devoted over
      the past 15 years to exploring the role of PAKs in a wide range of diseases, with
      a focus on oncology. Published PAK inhibitors are still comparatively rare and
      few exhibit satisfactory kinase selectivity and 'drug-like' properties. A key
      question is which profile, pan-PAK, group selective or isoform selective, holds
      the most promise from both therapeutic and safety standpoints. To investigate
      this question, isoform-selective, as well as kinome-selective, PAK inhibitor tool
      compounds will be needed. Pfizer was the first company to progress a PAK
      inhibitor (pan-PAK) to clinical development; it is expected that, despite the
      difficulties, other PAK inhibitors will soon follow.

PMID- 22404135
TI  - Microbial communities of urban stormwater sediments: the phylogenetic structure
      of bacterial communities varies with porosity.
AB  - This study focuses on the distribution of bacterial and fungal communities within
      the microstructure of a multi-contaminated sedimentary layer resulting from urban
      stormwater infiltration. Fractionation was performed on the basis of differential
      porosity and aggregate grain size, resulting in five fractions: leachable fitting
      macroporosity, < 10, 10-160, 160-1000 MUm fitting aggregates, > 1000 MUm. Amounts
      of both bacterial and fungal biomasses are greater in the < 10 MUm and leachable
      fractions. The aggregates contain numerous bacteria but very low amounts of
      fungal biomass. Single-strand conformational polymorphism molecular profiles
      highlighted the differences between bacterial and fungal communities of the
      leachable fraction and those of the aggregates. Random Sanger sequencing of ssu
      clones revealed that these differences were mainly because of the presence of
      Epsilonproteobacteria and Firmicutes in the leachable fractions, while the
      aggregates contained more Cyanobacteria. The Cyanobacteria phylotypes in the
      aggregates were dominated by the sequences related to Microcoleus vaginatus while
      the leachable fractions presented the sequences of chloroplastic origin.
      Therefore, more than 50% of the phylotypes observed were related to
      Proteobacteria while 40% were related to Cyanobacteria and Bacteroidetes.
      Preferential distribution of clades in almost all the phyla or classes detected
      was observed. This study provides insight into the identities of dominant members
      of the bacterial communities of urban sediments. Microcoleus vaginatus appeared
      to predominate in pioneer soils.

PMID- 22404136
TI  - Preparation and antimicrobial properties of gemini surfactant-supported triiodide
      complex system.
AB  - Iodine is an effective, simple, and inexpensive bactericide in disinfection.
      However, the poor solubility and stability of iodine in water limit its
      applications. In addition, the active iodine content in the commercial iodophors
      is quite low, and the reported triiodide complex is unstable. In this work, a
      long-term stable triiodide complex antimicrobial system was prepared by mixing
      iodine and a cationic gemini surfactant into lauryldimethylamine oxide (LDAO)
      aqueous solution, and its stability was examined by means of UV-vis
      spectrophotometry. It was found that the content of LDAO, cationic gemini
      surfactant and H(2)SO(4) played crucial roles in stabilizing antimicrobial
      system, and the active iodine (i.e., triiodide complex) content of the optimum
      formulation can remain stable for 150 days, as iodine is encapsulated by the
      mixed vesicles assembled by the protonated LDAO and the added gemini surfactant.
      However, the active iodine reduced rapidly when NaCl was added or the pH was
      increased in the environment. Furthermore, the antimicrobial efficacy of the
      optimized formulation was studied against Candida albicans, and more than 4 log
      reduction in viable cell after 5 min of contact was obtained.

PMID- 22404137
TI  - Subclinical orthostatic pulse pressure confirms mothers' ratings of ADHD in
      preschoolers.
AB  - Subclinical levels of orthostatic hypotension (OH) have been linked to a variety
      of emotional and behavioral outcomes across the life span. These connections are
      not surprising, given the multitude of correlated conditions, including autonomic
      control, cardiovascular functioning, baroreceptor activity, and dopamine and
      serotonin. The current study assessed blood pressure regulation in healthy
      preschool children ages 3-5 (n = 61). The Conner's Parent Rating Scale Revised
      was used to assess indexes of attention deficit hyperactivity disorder (ADHD).
      With the difference between standing and supine pulse pressure as the index of
      orthostatic blood pressure regulation, the results indicated that efficient pulse
      pressure regulation was significantly correlated with lower ADHD scores. Poorer
      orthostatic pulse pressure regulation in response to an orthostatic challenge may
      be a risk for symptoms of ADHD.

PMID- 22404138
TI  - Bacterial- and plant-type phosphoenolpyruvate carboxylase isozymes from
      developing castor oil seeds interact in vivo and associate with the surface of
      mitochondria.
AB  - Phosphoenolpyruvate carboxylase (PEPC) from developing castor oil seeds (COS)
      exists as two distinct oligomeric isoforms. The typical class-1 PEPC homotetramer
      consists of 107-kDa plant-type PEPC (PTPC) subunits, whereas the allosterically
      desensitized 910-kDa class-2 PEPC hetero-octamer arises from the association of
      class-1 PEPC with 118-kDa bacterial-type PEPC (BTPC) subunits. The in vivo
      interaction and subcellular location of COS BTPC and PTPC were assessed by
      imaging fluorescent protein (FP)-tagged PEPCs in tobacco suspension-cultured
      cells. The BTPC-FP mainly localized to cytoplasmic punctate/globular structures,
      identified as mitochondria by co-immunostaining of endogenous cytochrome oxidase.
      Inhibition of respiration with KCN resulted in proportional decreases and
      increases in mitochondrial versus cytosolic BTPC-FP, respectively. The FP-PTPC
      and NLS-FP-PTPC (containing an appended nuclear localization signal, NLS)
      localized to the cytosol and nucleus, respectively, but both co-localized with
      mitochondrial-associated BTPC when co-expressed with BTPC-FP. Transmission
      electron microscopy of immunogold-labeled developing COS revealed that BTPC and
      PTPC are localized at the mitochondrial (outer) envelope, as well as the cytosol.
      Moreover, thermolysin-sensitive BTPC and PTPC polypeptides were detected on
      immunoblots of purified COS mitochondria. Overall, our results demonstrate that:
      (i) COS BTPC and PTPC interact in vivo as a class-2 PEPC complex that associates
      with the surface of mitochondria, (ii) BTPC's unique and divergent intrinsically
      disordered region mediates its interaction with PTPC, whereas (iii) the PTPC
      containing class-1 PEPC is entirely cytosolic. We hypothesize that mitochondrial
      associated class-2 PEPC facilitates rapid refixation of respiratory CO(2) while
      sustaining a large anaplerotic flux to replenish tricarboxylic acid cycle C
      skeletons withdrawn for biosynthesis.

PMID- 22404140
TI  - Differential findings regarding molecular epidemiology of tuberculosis between
      two consecutive periods in the context of steady increase of immigration.
AB  - The demographic characteristics of the population of Madrid, with a steady
      increase in immigrants, from 4.7% in 1998 to 17.4% in 2007, provide an
      opportunity to study in depth the transmission of TB. Our aim was to compare two
      3-year longitudinal molecular studies of TB to define transmission patterns and
      predictors of clustering. Two prospective population-based molecular and
      epidemiological studies (2002-2004 and 2005-2007) of TB patients were conducted
      in nine urban districts in Madrid using the same methodology. During the period
      2002-2007, 2248 cases of TB were reported, and the incidence decreased from 23.5
      per 100,000 in 2002 to 20.8 in 2007 (p <0.001). A total of 1269 isolates were
      molecularly characterized and included in the study. The comparison between the
      two periods showed that the percentage of foreign-born patients among TB cases
      increased from 36.2% to 45.7% (p <0.001). Furthermore, the percentage of
      clustered cases decreased (36.6% vs. 30.6%; p 0.028), and this decline was
      associated with a decrease of clustered cases among men and people under 35
      years. We also observed a decrease in cases belonging to clusters containing >= 6
      people (14.2% vs. 8.2%; p <0.001), and in cases belonging to mixed clusters
      containing Spanish-born and foreign-born patients (18.5% vs. 11.1%, p <0.001).
      Our molecular epidemiology study provides clues to interpret the decrease in the
      incidence of TB in a context of steady increase of immigration. In our region,
      the decrease in the incidence of TB can be explained predominantly as a result of
      a decline in recent transmission.

PMID- 22404139
TI  - HIV-1 protease with 20 mutations exhibits extreme resistance to clinical
      inhibitors through coordinated structural rearrangements.
AB  - The escape mutant of HIV-1 protease (PR) containing 20 mutations (PR20) undergoes
      efficient polyprotein processing even in the presence of clinical protease
      inhibitors (PIs). PR20 shows >3 orders of magnitude decreased affinity for PIs
      darunavir (DRV) and saquinavir (SQV) relative to PR. Crystal structures of PR20
      crystallized with yttrium, substrate analogue p2-NC, DRV, and SQV reveal three
      distinct conformations of the flexible flaps and diminished interactions with
      inhibitors through the combination of multiple mutations. PR20 with yttrium at
      the active site exhibits widely separated flaps lacking the usual intersubunit
      contacts seen in other inhibitor-free dimers. Mutations of residues 35-37 in the
      hinge loop eliminate interactions and perturb the flap conformation. Crystals of
      PR20/p2-NC contain one uninhibited dimer with one very open flap and one closed
      flap and a second inhibitor-bound dimer in the closed form showing six fewer
      hydrogen bonds with the substrate analogue relative to wild-type PR. PR20
      complexes with PIs exhibit expanded S2/S2' pockets and fewer PI interactions
      arising from coordinated effects of mutations throughout the structure, in
      agreement with the strikingly reduced affinity. In particular, insertion of the
      large aromatic side chains of L10F and L33F alters intersubunit interactions and
      widens the PI binding site through a network of hydrophobic contacts. The two
      very open conformations of PR20 as well as the expanded binding site of the
      inhibitor-bound closed form suggest possible approaches for modifying inhibitors
      to target extreme drug-resistant HIV.

PMID- 22404141
TI  - Immunoselected STRO-3+ mesenchymal precursor cells and restoration of the
      extracellular matrix of degenerate intervertebral discs.
AB  - OBJECT: Chronic low-back pain of discal origin is linked strongly to disc
      degeneration. Current nonsurgical treatments are palliative and fail to restore
      the disc extracellular matrix. In this study the authors examined the capacity of
      ovine mesenchymal precursor cells (MPCs) to restore the extracellular matrix of
      degenerate discs in an ovine model. METHODS: Three adjacent lumbar discs of 24
      adult male sheep were injected intradiscally with chondroitinase-ABC (cABC) to
      initiate disc degeneration. The remaining lumbar discs were used as normal
      controls. Three months after cABC injection, the L3-4 discs of all animals were
      injected with either a high dose (4 * 10(6) cells, in 12 sheep) or low dose (0.5
      * 10(6) cells, in 12 sheep) of MPCs suspended in hyaluronic acid (HA). The
      adjacent L4-5 degenerate discs remained untreated; the L5-6 discs were injected
      with HA only. The animals were euthanized at 3 or 6 months after MPC injections
      (6 sheep from each group at each time point), and histological sections of the
      lumbar discs were prepared. Radiographs and MR images were obtained prior to cABC
      injection (baseline), 3 months after cABC injection (pretreatment), and just
      prior to necropsy (posttreatment). RESULTS: Injection of cABC decreased the disc
      height index (DHI) of target discs by 45%-50%, confirming degeneration. Some
      recovery in DHI was observed 6 months after treatment in all cABC-injected discs,
      but the DHI increased to within baseline control values only in the MPC-injected
      discs. This improvement was accompanied by a reduction in MRI degeneration
      scores. The histopathology scores observed at 3 months posttreatment for the high
      dose MPC-injected discs and at 6 months posttreatment for the low-dose MPC
      injected discs were significantly different from those of the noninjected and HA
      injected discs (p <0.001) but not from the control disc scores. CONCLUSIONS: On
      the basis of the findings of this study, the authors conclude that the injection
      of MPCs into degenerate intervertebral discs can contribute to the regeneration
      of a new extracellular matrix.

PMID- 22404143
TI  - Letter to the editor: unintended durotomy.

PMID- 22404142
TI  - The efficacy of minimally invasive discectomy compared with open discectomy: a
      meta-analysis of prospective randomized controlled trials.
AB  - OBJECT: Advocates of minimally invasive discectomy (MID) have promoted this
      operation as an alternative to open discectomy (OD), arguing that there may be
      less injury to the paraspinal muscles, decreased postoperative pain, and a faster
      recovery time. However, a recently published large randomized controlled trial
      (RCT) comparing these approaches reported inferior relief of leg pain in patients
      undergoing MID. The authors conducted a meta-analysis to evaluate complications
      and improvement in leg pain in patients with radiculopathy enrolled in RCTs
      comparing OD to MID. METHODS: The authors performed a literature search using
      Medline and EMBASE of studies indexed between January 1990 and January 2011.
      Predetermined RCT eligibility included the usage of tubular retractors during
      MID, a minimum follow-up duration of 1 year, and quantification of pain with the
      visual analog scale (VAS). Trials that only evaluated patients with recurrent
      disc herniation were excluded. Data on operative parameters, complications, and
      VAS scores of leg pain were extracted by 2 investigators. A meta-analysis was
      performed assuming random effects to determine the difference in mean change for
      continuous outcomes and the risk ratio for binary outcomes. RESULTS: Six trials
      comprising 837 patients (of whom 388 were randomized to MID and 449 were
      randomized to OD) were included. The mean operative time was 49 minutes during
      MID and 44 minutes during OD; this difference was not statistically significant.
      Incidental durotomies occurred significantly more frequently during MID (5.67%
      compared with 2.90% for OD; RR 2.05, 95% CI 1.05-3.98). Intraoperative
      complications (incidental durotomies and nerve root injuries) were also
      significantly more common in patients undergoing MID (RR 2.01, 95% CI 1.07-3.77).
      The mean preoperative VAS score for leg pain was 6.9 in patients randomized to
      MID and 7.2 in those randomized to OD. With long-term follow-up (1-2 years
      postoperatively), the mean VAS score improved to 1.6 in both the MID and OD
      cohorts. There was no significant difference in relief of leg pain between the 2
      approaches with either short-term follow-up (2-3 months postoperatively, 0.81
      points on the VAS, 95% CI -4.71 to 6.32) or long-term follow-up (2.64 on the VAS,
      95% CI -2.15 to 7.43). Reoperation for recurrent herniation was more common in
      patients randomized to the MID group (8.50% compared with 5.35% in patients
      randomized to the OD group), but this difference was not statistically
      significant (RR 1.56, 95% CI 0.92-2.66). Total complications did not differ
      significantly between the operations (RR 1.50, 95% CI 0.97-2.33). CONCLUSIONS:
      The current evidence suggests that both OD and MID lead to a substantial and
      equivalent long-term improvement in leg pain. Adequate decompression, regardless
      of the operative approach used, may be the primary determinant of pain relief-the
      major complaint of many patients with radiculopathy. Incidental durotomies
      occurred significantly more frequently during MID, but total complications did
      not differ between the techniques.

PMID- 22404144
TI  - Minimally invasive lateral extracavitary corpectomy: cadaveric evaluation model
      and report of 3 clinical cases.
AB  - OBJECT: In this paper, the authors' goal was to demonstrate the clinical and
      technical nuances of a minimally invasive lateral extracavitary approach (MI
      LECA) for thoracic corpectomy and anterior column reconstruction. METHODS: A
      cadaveric feasibility study and the subsequent application of this approach in 3
      clinical cases are reported. Six procedures were completed in 3 human cadavers.
      Minimally invasive, extrapleural thoracic corpectomies were performed with the
      aid of a 24-mm tubular retraction system, using a posterolateral incision and an
      oblique approach angle. Fluoroscopy and postprocedural CT scanning, using 3D
      volumetric averaging software, was used to evaluate the degree of bone removal
      and decompression. Three clinical cases, including a T-11 burst fracture, a T-7
      plasmacytoma, and a T4-5 vertebral body (VB) tuberculosis lesion, were treated
      using the approach. RESULTS: At 6 cadaveric levels, the mean circumferential
      volumetric decompression was 48% +/- 16%, and the mean resection of the VB was
      72% +/- 13%. The mean change in anterior and posterior vertebral height with
      expansion of the corpectomy cage was 47 and 61 mm, respectively. There were no
      violations of the pleura or dura. Pedicle screw reliability was 95.8% (23 of 24
      screws) with a single lateral breach. All 3 patients in the clinical cohort had
      excellent clinical outcomes. There was a single pleural tear requiring chest tube
      drainage. Operative images and a video clip are provided to illustrate the
      approach. CONCLUSIONS: A minimally invasive lateral extracavitary thoracic
      corpectomy has the ability to provided excellent spinal cord decompression and VB
      resection. The procedure can be completed safely and successfully with minimal
      blood loss and little associated morbidity. This approach has the potential to
      improve upon established traditional open corridors for posterolateral thoracic
      corpectomy.

PMID- 22404146
TI  - Assessment of pain in sedated and mechanically ventilated patients: an
      observational study.
AB  - BACKGROUND: Critically ill patients often undergo unpleasant procedures. We
      quantified the effects of an unpleasant stimulus on physiological and behavioral
      parameters and evaluated how they are modified by sedation and analgesia.
      METHODS: A 6-month study in the 30-bed intensive care unit (ICU) of a university
      hospital examined 21 sedated patients from various diagnostic groups. Hemodynamic
      and respiratory parameters, pupil size, facial expression, muscle tone, body
      movement, and the Richmond Agitation-Sedation Scale (RASS) score were measured
      before and during intratracheal suctioning, first in sedated patients, after
      sedation was stopped, and after an opioid bolus. RESULTS: Before intratracheal
      suctioning, patients had RASS scores of -1.8 +/- 1.2 (mean +/- standard
      deviation; sedation), -0.6 +/- 1.7 (sedation stop), and -0.9 +/- 1.4 (analgesia)
      (P = 0.014). Intratracheal suctioning significantly increased RASS during both
      sedation (to -0.6 +/- 1.7) and sedation stop (to 1.0 +/- 1.5) (both P < 0.01),
      but not during analgesia. Systolic blood pressure increased during sedation (by 9
      +/- 10 mmHg), during sedation stop (by 15 +/- 17 mmHg) and during analgesia (by 9
      +/- 4 mmHg; all P < 0.01), but diastolic pressure only during sedation and
      sedation stop (both P < 0.01). Facial expression, body movement, and muscle tone
      changed significantly during the episodes of intratracheal suctioning. Heart
      rate, tidal volume, and pupil size remained stable under all conditions.
      CONCLUSIONS: Intratracheal suctioning evoked significant changes in some
      physiological and behavioral parameters. Some physiological changes were
      suppressed by analgesia, but at our ICU's standard doses, neither analgesia nor
      sedation attenuated changes in behavioral parameters at the intensity tested.

PMID- 22404145
TI  - Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in
      humans.
AB  - BACKGROUND AND PURPOSE: The use of +/- 3,4-methylenedioxymethamphetamine (MDMA,
      'ecstasy') is associated with cardiovascular complications and hyperthermia.
      EXPERIMENTAL APPROACH: We assessed the effects of the alpha(1) - and beta
      adrenoceptor antagonist carvedilol on the cardiostimulant, thermogenic and
      subjective responses to MDMA in 16 healthy subjects. Carvedilol (50 mg) or
      placebo was administered 1 h before MDMA (125 mg) or placebo using a randomized,
      double-blind, placebo-controlled, four-period crossover design. KEY RESULTS
      Carvedilol reduced MDMA-induced elevations in blood pressure, heart rate and body
      temperature. Carvedilol did not affect the subjective effects of MDMA including
      MDMA-induced good drug effects, drug high, drug liking, stimulation or adverse
      effects. Carvedilol did not alter the plasma exposure to MDMA. CONCLUSIONS AND
      IMPLICATIONS: alpha(1) - and beta-Adrenoceptors contribute to the cardiostimulant
      and thermogenic effects of MDMA in humans but not to its psychotropic effects.
      Carvedilol could be useful in the treatment of cardiovascular and hyperthermic
      complications associated with ecstasy use.

PMID- 22404147
TI  - Biomimetic silver-containing colloids of poly(2-methacryloyloxyethyl
      phosphorylcholine) and their film-formation properties.
AB  - The synthesis of stable dispersions of hybrid colloids comprising copolymers of
      biocompatible 2-hydroxyethyl methacrylate (HEMA) and zwitterionic, biomimetic 2
      methacryloyloxyethyl phosphorylcholine (MPC) incorporating antibacterial AgBF(4)
      by inverse miniemulsion is described. The prepared hybrid colloids were designed
      to provide both antibacterial and antifouling properties for the formation of
      interesting, multifunctional films. The obtained particles had sizes in the range
      of 130-160 nm with two different weight ratios of MPC to HEMA (1:10 and 2:5) and
      AgBF(4) contents between 0% and 15%. The silver salt takes on the role of the
      lipophobe in stabilizing the miniemulsion droplets against Ostwald ripening and
      is reduced after polymerization to Ag nanoparticles by gaseous hydrazine.
      Subsequently, the hybrid particles are transformed into smooth and stable films
      with thicknesses between 145 and 225 nm by simple drop casting and solvent
      annealing. The dispersions and films were thoroughly characterized by DLS, TEM,
      SEM, EDX, TGA, UV-vis spectroscopy, ICP-OES, XRD, AFM, and contact angle
      measurements. After immersion into water, the films did not show detectable
      leakage of silver, so they could be employed as dual-functional antifouling and
      antibacterial coatings.

PMID- 22404148
TI  - Nucleoside and nucleobase analogs in cancer treatment: not only sapacitabine, but
      also gemcitabine.
AB  - Nucleoside analogs are widely used for treatment of various malignancies.
      Benchmark drugs are cytarabine for acute myeloid leukemia and gemcitabine for
      pancreatic and lung cancer. Sapacitabine is a novel cytidine analog currently in
      development. This editorial focuses on the potential of new nucleoside analogs
      and on novel possibilities of gemcitabine. Gemcitabine is a nucleoside analog
      with many faces, which shows a remarkable activity in a variety of cancers, most
      likely because it has a unique metabolism, a so-called self-potentiation.
      Gemcitabine is taken up by nucleoside transporters, is activated by deoxycytidine
      kinase and incorporated into both RNA and DNA. Inhibition of ribonucleotide
      reductase and dCMP deaminase enhances its activation, while cytidine deaminase
      converts gemcitabine to its presumably inactive metabolite 2',2'
      difluorodeoxyuridine, which in its nucleotide form may inhibit thymidylate
      synthase. Gemcitabine is widely used in combination, predominantly with a
      platinum analog, with other combinations less frequently used or being explored.
      Standard administration of gemcitabine is with a 30-min weekly infusion at 1000
      mg/m(2), but alternatives are being explored such as prodrugs (e.g., CO-1.01,
      which can bypass transport deficiency), the fixed-dose rate infusion (10
      mg/m(2)/min), and local routes of administration by a 24-h hepatic artery
      infusion, by instillation in the bladder or by intraperitoneal administration to
      treat advanced ovarian cancer. Other alternatives for combinations of gemcitabine
      in ovarian cancer consist of increasing the inhibition of ribonucleotide
      reductase with triapine or hydroxyurea. Gemcitabine's action on signaling also
      provides a rational concept for combination with signal transduction pathways.

PMID- 22404149
TI  - Late cytotoxic edema in 2 children with hemiplegia: hemiplegic migraine or
      stroke?
AB  - Hemiplegic migraine (HM) is a rare variant of migraine with aura, characterized
      by migrainous headache and fully reversible motor deficit within 24 hours. Both
      sporadic and familial forms of HMs are genetically heterogenous with little
      information on neuroimaging during and after acute attacks. We report 2 cases of
      children with presumed HM and late cytotoxic edema.

PMID- 22404151
TI  - The combination of bortezomib and dexamethasone is an efficient therapy for
      relapsed/refractory scleromyxedema: a rare disease with new clinical insights.
AB  - Scleromyxedema (SM) is a rare primary cutaneous inflammatory mucinosis
      characterised by papular mucinosis, monoclonal gammopathy and extracutaneous
      involvement. Most therapeutic options have failed in SM but high-dose therapy
      followed by autologous peripheral blood stem cell transplantation (APBSCT)
      appears to be highly effective, although SM normally relapses. We report the case
      of a 29-yr-old patient with severe SM who achieved stringent complete response
      with Bortezomib plus Dexamethasone after an early relapse subsequent to a high
      dose melphalan regimen followed APBSCT. It is of particular note that
      dermatological lesions responded to both therapies before M-component
      modifications, suggesting that SM is independent of M-component characteristics.
      However, treatment should be directed towards the underlying plasma cell
      malignancy with typical anti-myeloma agents.

PMID- 22404150
TI  - Proteome differences between male and female fetal cells in amniotic fluid.
AB  - In mammals, sex development is genetically and hormonally regulated. The process
      starts with the establishment of chromosomal structures (XY or XX), followed by
      the expression of sex-dependent genes. In order to elucidate the differential
      protein profiles between male and female amniocytes, a proteomic approach has
      been performed in this study. Here, we utilized a proteomics-based approach
      including 2D-DIGE and MALDI-TOF MS analysis to obtain differentially expressed
      proteins between male and female amniocytes. After resolving protein samples with
      2D-DIGE technique, 45 proteins corresponding to 28 unique proteins were
      differentially expressed between male and female amninocytes from three
      independent batches of amniotic fluid. Of all of these unique identified spots,
      five of them (annexin A1, cathepsin D, cytoskeletal 19, protein disulfide
      isomerase, and vimentin) exhibited more than 1.5-fold upregulation or
      downregulation in at least two independent experiments. Importantly, the
      identified proteins involved in protein degradation and protein folding display
      upregulated in male amniocytes, implying the differential regulations of protein
      degradation and protein folding during sex development. In conclusion, the
      identified differentially expressed proteins may be employed as potential
      signatures for the sex development. Moreover, the established proteomic platform
      might further utilize to discover the potential biomarkers for the prenatal
      genetic disorders in fetus.

PMID- 22404152
TI  - Patterns and determinants of leisure participation of youth and adults with
      developmental disabilities.
AB  - BACKGROUND: People with developmental disabilities are at high risk for a limited
      participation in leisure activities. The aim of this study was to investigate the
      participation in, preference for and interest in leisure activities of young and
      adults with developmental disabilities, and to examine the factors associated
      with leisure activity. METHODS: A cross-sectional design was used with a
      convenience sample of 237 people aged 17 to 65, living in the community. Leisure
      participation was assessed with the Spanish version of Leisure Assessment
      Inventory. Percentages were calculated by types of activity, and repeated
      measures anovas were used to analyse the differences between types of activities,
      and mixed anovas to analyse the factors that explain differences in leisure
      activity participation, preference and interest. RESULTS: Leisure social
      activities and recreation activities at home were mostly solitary and passive in
      nature and were identified as those being most commonly engaged in. Respondents
      expressed preference for more social and physical activity, and they were
      interested in trying out a large number of physical activities. Age and type of
      schooling determine participation in leisure activity. The results underscore the
      differences in leisure activity participation, preference and interest depending
      on the severity of the disability. CONCLUSIONS: The findings reveal interesting
      patterns of participation in leisure activities from the viewpoint of youngsters
      and adults with developmental disabilities. Leisure participation among people
      with developmental disabilities is likely to be more affected by environmental
      factors than by personal factors.

PMID- 22404153
TI  - Anomalous chord of the left atrium without involvement of the mitral valve.
AB  - An anomalous chord from the left side of the atrial septum to the left atrial
      free wall was incidentally noted on transthoracic echocardiography in a 14-year
      old boy with vasovagal syncope. Previously reported cases of anomalous chords in
      the left atrium were associated with the mitral valve leaflets in all but two
      cases. This is the first reported case of an echocardiographic diagnosis of
      anomalous left atrial chord without insertion of the chord into the mitral valve.

PMID- 22404154
TI  - Ethical decision-making in neonatology - a Scandinavian perspective.

PMID- 22404155
TI  - Radiosensitization effect of poly(ADP-ribose) polymerase inhibition in cells
      exposed to low and high liner energy transfer radiation.
AB  - Poly(ADP-ribose) polymerase (PARP)-1 promotes base excision repair and DNA strand
      break repair. Inhibitors of PARP enhance the cytotoxic effects of gamma
      irradiation and X-irradiation. We investigated the impact of PARP inhibition on
      the responses to gamma-irradiation (low liner energy transfer [LET] radiation)
      and carbon-ion irradiation (high LET radiation) in the human pancreatic cancer
      cell line MIA PaCa-2. Cell survival was assessed by colony formation assay after
      combination treatment with the PARP inhibitor AZD2281 and single fraction gamma
      irradiation and carbon-ion irradiation (13 and 70 keV/MUm [LET 13 and LET 70]).
      The DNA damage response (DDR) was assessed by pulse field gel electrophoresis,
      western blotting and flow cytometry. Treatment with a PARP inhibitor enhanced the
      cytotoxic effect of gamma-irradiation and LET 13 and LET 70 carbon-ion
      irradiation. Moreover, the radiosensitization effect was greater for LET 70 than
      for LET 13 irradiation. Prolonged and increased levels of gamma-H2AX were
      observed both after gamma-irradiation and carbon-ion irradiation in the presence
      of the PARP inhibitor. Enhanced level of phosphorylated-p53 (Ser-15) was observed
      after gamma-irradiation but not after carbon-ion irradiation. PARP inhibitor
      treatment induced S phase arrest and enhanced subsequent G2/M arrest both after
      gamma-irradiation and carbon-ion irradiation. These results suggest that the
      induction of S phase arrest through an enhanced DDR and a local delay in DNA
      double strand break processing by PARP inhibition caused sensitization to gamma
      irradiation and carbon-ion irradiation. Taken together, PARP inhibitors might be
      applicable to a wide therapeutic range of LET radiation through their effects on
      the DDR.

PMID- 22404156
TI  - Clinical and economic impact of adhesiolysis during repeat cesarean delivery.
AB  - OBJECTIVE: To estimate adhesiolysis rates at cesarean delivery (CD) and to
      estimate costs and clinical implications of performing adhesiolysis at repeat CD.
      DESIGN: Retrospective cohort using secondary data. SETTING: Over 500 acute care
      hospitals in the USA. POPULATION: Women >=15 years old with a medical claim for
      CD between 1 January 2007 and 31 December 2008 who were treated in a hospital
      that contributed data to the Premier PerspectiveTM database. METHODS: Using data
      from hospital discharge records, rates of adhesiolysis at the time of CD were
      calculated. Among patients with repeat CD, a propensity score was used to create
      matched cohorts with and without adhesiolysis. Unadjusted rates and means were
      compared between these cohorts. MAIN OUTCOME MEASURES: Cost, length of stay and
      selected clinical complications between repeat CD patients with and without
      adhesiolysis. RESULTS: Adhesiolysis was performed in 0.5% of primary and 6.1% of
      repeat CD patients. Using propensity scores, 10 261 women who experienced repeat
      CD with adhesiolysis were matched to 10 261 control women. Hospital cost ($5739
      vs. $5448), length of stay (2.97 vs. 2.88 days) and operative time (84.0 vs. 74.2
      min) were significantly greater in the adhesiolysis than in the non-adhesiolysis
      group (p < 0.01 for all comparisons), as was the overall complication rate (6.3
      vs. 3.5%). CONCLUSIONS: Adhesiolysis rates were higher in repeat compared with
      primary CD. Among repeat CD patients, costs and complications were higher in the
      adhesiolysis group. Reducing adhesion formation after primary CD could reduce
      cost and complications at the time of repeat CD.

PMID- 22404158
TI  - Clarifying Erb's point as an anatomic landmark in the posterior cervical
      triangle.

PMID- 22404159
TI  - Impact of fluorochrome stains used to study bacterial transport in shallow
      aquifers on motility and chemotaxis of Pseudomonas species.
AB  - One of the most common methods of tracking movement of bacteria in groundwater
      environments involves a priori fluorescent staining. A major concern in using
      these stains to label bacteria in subsurface injection-and-recovery studies is
      the effect they may have on the bacterium's transport properties. Previous
      studies investigated the impact of fluorophores on bacterial surface properties
      (e.g. zeta potential). However, no previous study has looked at the impact of
      fluorescent staining on swimming speed and chemotaxis. It was found that DAPI
      lowered the mean population swimming speed of Pseudomonas putida F1 by 46% and
      Pseudomonas stutzeri by 55%. DAPI also inhibited the chemotaxis in both strains.
      The swimming speeds of P. putida F1 and P. stutzeri were diminished slightly by
      CFDA/SE, but not to a statistically significant extent. CFDA/SE had no effect on
      chemotaxis of either strain to acetate. SYBR((r)) Gold had no effect on swimming
      speed or the chemotactic response to acetate for either strain. This research
      indicates that although DAPI may not affect sorption to grain surfaces, it
      adversely affects other potentially important transport properties such as
      swimming and chemotaxis. Consequently, bacterial transport studies conducted
      using DAPI are biased to nonchemotactic conditions and do not appear to be
      suitable for monitoring the effect of chemotaxis on bacterial transport in
      shallow aquifers.

PMID- 22404161
TI  - Thermal stability of structurally different viruses with proven or potential
      relevance to food safety.
AB  - AIMS: To collect comparative data on thermal stability of structurally different
      viruses with proven or potential relevance to food safety. METHODS AND RESULTS:
      Suspensions with poliovirus Sabin1, adenovirus type5, parechovirus1, human
      norovirus (NoV) GII.4, murine NoV (MNV1) and human influenza A (H1N1) viruses
      were heated at 56 and 73 degrees C. Infectivity was tested by culture assay for
      all but human NoV GII.4 that cannot be cultivated in vitro. Time to first log(10)
      reduction (TFL-value) was calculated based on best fit using the monophasic,
      biphasic or Weibull models. The Weibull model provided the best fit at 56 degrees
      C for all viruses except influenza virus. The TFL at 56 degrees C varied between
      a high of 27 min (parechovirus) to a low of 10 s (adenovirus) and ranked
      parechovirus > influenza > MNV1 > poliovirus > adenovirus. The monophasic model
      best described the behaviour of the viruses at 73 degrees C, in which case the
      TFL was MNV1(62s) > influenza > adenovirus > parechovirus > poliovirus(14s).
      CONCLUSIONS: Viruses do not follow log-linear thermal inactivation kinetics and
      the thermostability of parechovirus and influenza virus is similar to that of
      proven foodborne viruses. SIGNIFICANCE AND IMPACT OF THE STUDY: Resistant
      fractions of viruses may remain infectious in thermal inactivation processes and
      inactivation of newly discovered or enveloped viruses in thermal food preparation
      processes should not be assumed without further testing.

PMID- 22404160
TI  - Targeting frameshifting in the human immunodeficiency virus.
AB  - INTRODUCTION: HIV-1 uses a programmed -1 ribosomal frameshift to generate Gag
      Pol, the precursor of its enzymes, when its full-length mRNA is translated by the
      ribosomes of the infected cells. This change in the reading frame occurs at a so
      called slippery sequence that is followed by a specific secondary structure, the
      frameshift stimulatory signal. This signal controls the frameshift efficiency.
      The synthesis of HIV-1 enzymes is critical for virus replication and therefore,
      the -1 ribosomal frameshift could be the target of novel antiviral drugs. AREAS
      COVERED: Various approaches were used to select drugs interfering with the -1
      frameshift of HIV-1. These include the selection and modification of chemical
      compounds that specifically bind to the frameshift stimulatory signal, the use of
      antisense oligonucleotides targeting this signal and the selection of compounds
      that modulate HIV-1 frameshift, by using bicistronic reporters where the
      expression of the second cistron depends upon HIV-1 frameshift. EXPERT OPINION:
      The most promising approach is the selection and modification of compounds
      specifically targeting the HIV-1 frameshift stimulatory signal. The use of
      antisense oligonucleotides binding to the frameshift stimulatory signal is still
      questionable. The use of bicistronic reporters preferentially selects compounds
      that modulate the frameshift by targeting the ribosomes, which is less promising.

PMID- 22404162
TI  - Lability criteria in diffusive gradients in thin films.
AB  - The penetration of metal complexes into the resin layer of DGT (diffusive
      gradients in thin films) devices greatly influences the measured metal
      accumulation, unless the complexes are either totally inert or perfectly labile.
      Lability criteria to predict the contribution of complexes in DGT measurements
      are reported. The key role of the resin thickness is highlighted. For complexes
      that are partially labile to the DGT measurement, their dissociation inside the
      resin domain is the main source of metal accumulation. This phenomenon explains
      the practical independence of the lability degree of a complex in a DGT device
      with respect to the ligand concentration. Transient DGT regimes, reflecting the
      times required to replenish the gel and resin domains up to the steady-state
      profile of the complex, are also examined. Low lability complexes (lability
      degree between 0.1 and 0.2) exhibit the longest transient regimes and therefore
      require longer deployment times to ensure accurate DGT measurements.

PMID- 22404163
TI  - Isolated ventricular noncompaction: implications for mechanisms of sudden cardiac
      death.
AB  - We present a case of a young patient, whose first manifestation of isolated
      ventricular noncompaction (IVNC) was sudden cardiac arrest precipitated by
      ventricular fibrillation. Furthermore we had the rare opportunity to record the
      onset of subsequent episodes of ventricular fibrillation-with discussion on the
      mechanisms of ventricular arrhythmias in IVNC.

PMID- 22404164
TI  - Acquisition and generalization of fear conditioning are not modulated by the BDNF
      val66met polymorphism in humans.
AB  - Few studies have investigated the role of the BDNF-val66met polymorphism in fear
      conditioning in humans, and previous results have been inconsistent. In the
      present study, we examined whether the BDNF-val66met was associated with
      differences in the acquisition and generalization of fear during a differential
      conditioning paradigm in a large sample of participants (N = 141). Using three
      different indexes of fear learning (fear-potentiated startle, skin conductance
      response, and online risk ratings) no effects of the BDNF-val66met were found
      either on the acquisition or the generalization of conditioned fear. Taken
      together with previous data, our study suggests that the BDNF-val66met
      polymorphism has no effect on the acquisition or generalization of fear.

PMID- 22404165
TI  - Chemistry at the Dirac point: Diels-Alder reactivity of graphene.
AB  - Most of the interesting physics of graphene results from the singular electronic
      band structure at the so-called Dirac point, where the conduction and valence
      bands cross in momentum space. Although graphene is very stable
      thermodynamically, the electronic structure at the Dirac point facilitates basal
      plane chemistry including pericyclic reactions such as the Diels-Alder reaction. 
      We have discovered a series of facile Diels-Alder reactions in which graphene can
      function either as a diene when paired with tetracyanoethylene and maleic
      anhydride or as a dienophile when paired with 2,3-dimethoxybutadiene and 9
      methylanthracene. In this Account, we seek to rationalize these findings using
      simple arguments based on considerations of orbital symmetry and the frontier
      molecular orbital theory.  The graphene conduction and valence bands (HOMO and
      LUMO) cross at the Dirac point, which defines the work function (W = 4.6 eV).
      Thus, the HOMO and LUMO form a degenerate pair of orbitals at this point in
      momentum space with the same ionization potential (IP) and electron affinity
      (EA). Based on the importance of the energies of the HOMO (-IP) and LUMO (-EA) in
      frontier molecular orbital (FMO) theory, graphene should be a reactive partner in
      Diels-Alder reactions due to the very high-lying HOMO and low-lying LUMO
      (energies of -4.6 eV). Inspection of the orbital symmetries of the degenerate
      pair of half-occupied band orbitals at the Dirac point confirms that with the
      appropriate orbital occupancies, both diene and dienophile reaction partners
      should undergo concerted Diels-Alder reactions with graphene that are allowed
      based on the Woodward-Hoffmann principles of orbital symmetry.

PMID- 22404166
TI  - Systems of creation: the emergence of life from nonliving matter.
AB  - The advent of life from prebiotic origins remains a deep and possibly
      inexplicable scientific mystery. Nevertheless, the logic of living cells offers
      potential insights into an unknown world of autonomous minimal life forms
      (protocells). This Account reviews the key life criteria required for the
      development of protobiological systems. By adopting a systems-based perspective
      to delineate the notion of cellularity, we focus specific attention on core
      criteria, systems design, nanoscale phenomena and organizational logic.  Complex
      processes of compartmentalization, replication, metabolism, energization, and
      evolution provide the framework for a universal biology that penetrates deep into
      the history of life on the Earth. However, the advent of protolife systems was
      most likely coextensive with reduced grades of cellularity in the form of simpler
      compartmentalization modules with basic autonomy and abridged systems
      functionalities (cells focused on specific functions such as metabolism or
      replication). In this regard, we discuss recent advances in the design, chemical
      construction, and operation of protocell models based on self-assembled
      phospholipid or fatty acid vesicles, self-organized inorganic nanoparticles, or
      spontaneous microphase separation of peptide/nucleotide membrane-free droplets.
      These studies represent a first step towards addressing how the transition from
      nonliving to living matter might be achieved in the laboratory. They also
      evaluate plausible scenarios of the origin of cellular life on the early Earth.
      Such an approach should also contribute significantly to the chemical
      construction of primitive artificial cells, small-scale bioreactors, and soft
      adaptive micromachines.

PMID- 22404167
TI  - The C-terminus of the G protein alpha subunit controls the affinity of
      nucleotides.
AB  - The C-terminus of the G protein alpha subunit has a well-known role in
      determining the selective coupling with the cognate G protein-coupled receptor
      (GPCR). In fact, rhodopsin, a prototypical GPCR, exhibits active state
      [metarhodopsin II (MII)] stabilization by interacting with G protein [extra
      formation of MII (eMII)], and the extent of stabilization is affected by the C
      terminal sequence of Galpha. Here we examine the relationship between the amount
      of eMII and the activation efficiency of Gi mutants whose Gialpha forms have
      different lengths of the C-terminal sequence of Goalpha. The results show that
      both the activation efficiencies of Gi and the amounts of eMII were affected by
      mutations; however, there was no correlation between them. This finding suggested
      that the C-terminal region of Galpha not only stabilizes MII (active state) but
      also affects the nucleotide-binding site of Galpha. Therefore, we measured the
      activation efficiency of these mutants by MII at several concentrations of GDP
      and GTP and calculated the rate constants of GDP release, GDP uptake, and GTP
      uptake. These rate constants of the Gi mutants were substantially different from
      those of the wild type, indicating that the replacement of the amino acid
      residues in the C-terminus alters the affinity of nucleotides. The rate constants
      of GDP uptake and GTP uptake showed a strong correlation, suggesting that the C
      terminus of Gialpha controls the accessibility of the nucleotide-binding site.
      Therefore, our results strongly suggest that there is a long-range interlink
      between the C-terminus of Gialpha and its nucleotide-binding site.

PMID- 22404168
TI  - 14-3-3 proteins regulate the intracellular localization of the transcriptional
      activator GmMYB176 and affect isoflavonoid synthesis in soybean.
AB  - Isoflavonoids are legume-specific natural plant compounds that play important
      functions in nitrogen fixation as well as biotic and abiotic stress responses.
      Many clinical studies have suggested a role for isoflavonoids in human health and
      nutrition. We have recently identified an R1 MYB transcription factor GmMYB176
      that regulates CHS8 gene expression and isoflavonoid biosynthesis. Here we
      demonstrate that binding of 14-3-3 proteins to GmMYB176 modulates this function.
      GmMYB176 interacts with all 16 14-3-3 proteins (SGF14s) in soybean (Glycine max)
      with varying activity. The detailed analysis of 14-3-3-binding sites within
      GmMYB176 identified a critical motif (D2) where Ser29 is potentially
      phosphorylated. Deletion of the D2 motif from GmMYB176 or substitution of Ser29
      with an alanine abolished binding with SGF14 proteins, which altered the
      subcellular localization of GmMYB176. Overexpression of SGF14l in soybean hairy
      roots did not affect the transcript level of GmMYB176 but it reduced the
      expression levels of key isoflavonoid genes and isoflavonoid accumulation in
      soybean hairy root. Our results suggest that SGF14-GmMYB176 interaction regulates
      the intracellular localization of GmMYB176, thereby affecting isoflavonoid
      biosynthesis in soybean.

PMID- 22404169
TI  - NDM-1, OXA-48 and OXA-181 carbapenemase-producing Enterobacteriaceae in Sultanate
      of Oman.
AB  - Twenty-two carbapenem-resistant enterobacterial isolates were recovered from
      patients hospitalized between October 2010 and March 2011 at the Royal Hospital
      of Muscat, Sultanate of Oman. Eleven NDM-1, five OXA-48 and one NDM-1 plus OXA
      181 producers of diverse ST types were recovered from clinical samples. All
      carbapenemase genes were located on self-conjugative plasmids and were nearly
      always associated with other resistance determinants, including extended-spectrum
      beta-lactamases and the ArmA methylase encoding resistance to aminoglycosides.
      This work highlights the dissemination of NDM-1 and OXA-48-type producers in the
      Middle East.

PMID- 22404170
TI  - Maternal and paternal alcohol misuse and alcohol-related outcomes among college
      students.
AB  - Using a large college student sample (N = 1,095), the present study examined
      whether the relationship between parental alcohol abuse and offspring alcohol use
      varied as a function of parent and offspring gender, and whether the relationship
      to the non-substance-abusing mother or father buffered against the risk
      associated with being an adult child of an alcoholic (ACOA). Among women,
      maternal ACOAs (i.e., the mother only was suspected of alcohol misuse) had the
      greatest risk of problematic alcohol consumption, whereas among men, both parent
      ACOAs (i.e., both parents were suspected of alcohol misuse) had the greatest risk
      of problematic alcohol consumption. No support was found for the buffering
      hypothesis. We discuss implications of our findings and future directions.

PMID- 22404171
TI  - Pelvic organ prolapse contributes to sexual dysfunction: a cross-sectional study.
AB  - OBJECTIVE: To evaluate the effect of pelvic organ prolapse (POP) on female sexual
      dysfunction. DESIGN: Cross-sectional, observational study. SETTING: Gynecological
      outpatient and urogynecological university clinics in Greece. POPULATION: One
      hundred and one women with POP seen in the urogynecology clinic (study group) and
      70 women without POP seen in the gynecology outpatient department (control
      group). METHODS: Women with and without POP completed a condition-specific sexual
      dysfunction questionnaire (DYSQ) comprising four domains: sexual behavior;
      physical problems other than urinary incontinence; urinary incontinence problems;
      and satisfaction. Pelvic organ prolapse was assessed by the International
      Continence Society Pelvic Organ Prolapse Quantification System grading system.
      The primary outcome of the study was the assessment of sexual function by DYSQ in
      women with and without POP. MAIN OUTCOME MEASURES: We compared sexual function in
      women with and without POP and evaluated the extent of the effect of various
      grades of POP on sexual function. RESULTS: One hundred and seventy-one women were
      recruited, 101 in the POP group and 70 in the control group. The total and factor
      specific DYSQ scores in the POP group were worse than those in the control group
      (p < 0.001) but did not seem to worsen with an increasing grade of prolapse.
      Linear regression showed that the best model to describe the DYSQ score includes
      the presence of POP and years of menopause. These variables explain 15.6% of the
      total variability in DYSQ scores. CONCLUSIONS: The presence of prolapse only
      partly explains impaired sexual functioning in women with POP. Sexual dysfunction
      is related to the presence of POP and not the grade of POP.

PMID- 22404172
TI  - Simple reductant concentration-dependent shape control of polyhedral gold
      nanoparticles and their plasmonic properties.
AB  - We report a facile seed-mediated method for the synthesis of monodisperse
      polyhedral gold nanoparticles, with systematic shape evolution from octahedral to
      trisoctahedral structures. The control over the particle growth process was
      achieved simply by changing the concentration of the reductant in the growth
      solution, in the presence of small spherical seed nanoparticles. By progressively
      increasing the concentration of the reductant used in the growth solution
      (ascorbic acid), while keeping the amount and type of added surfactant constant,
      the morphology of the gold nanoparticles was varied from octahedral to truncated
      octahedral, cuboctahedral, truncated cubic, cubic, and finally trisoctahedral
      structures. These nanoparticles were monodisperse in size, possessed similar
      volumes, and were naturally oriented so that their larger crystal planes were
      face down on quartz substrates when deposited from the solution. By adjusting the
      volume of gold seed nanoparticle solution added to a growth solution, the size of
      the simplest gold nanoparticles (with a highly symmetric cubic morphology) could
      be tuned from 50 +/- 2.1 to 112 +/- 11 nm. When other seed nanoparticles were
      used, the size of the cubic Au nanoparticles reached 169 +/- 7.0 nm. The
      nanoparticle growth mechanism and the plasmonic properties of the resulting
      polyhedral nanoparticles are discussed in this paper.

PMID- 22404173
TI  - Cancer diagnoses in Iraqi refugees.

PMID- 22404175
TI  - Tongue-tie, breastfeeding difficulties and the role of Frenotomy.
AB  - A greater emphasis on exclusive breastfeeding in recent years has re-ignited the
      historical debate over the role of ankyloglossia (tongue-tie) in infants with
      breastfeeding difficulties. Several prospective cohort studies and randomized
      control trials have been published in this area in the last 10-15 years. We
      critically evaluated recent evidence and attempted to answer two important
      clinical queries in this area, that is, (i) whether ankyloglossia is associated
      with breastfeeding difficulties and (ii) whether frenotomy helps mother-baby dyad
      in such setting? CONCLUSION: Neonates with tongue-tie are at increased risk for
      breastfeeding difficulties. An early recognition of this association by primary
      care provider and prompt referral to a lactation consultant is important. In
      cases with clearly documented breastfeeding difficulties, frenotomy often results
      in rapid improvement in symptoms.

PMID- 22404176
TI  - Migraine headaches and suicide attempt.
AB  - BACKGROUND: Previous cross-sectional studies reported an increased risk of
      suicide attempt in persons with migraine headache, which was sustained when
      psychiatric comorbidity was statistically controlled. OBJECTIVE: To estimate the
      risk of suicide attempt in persons with migraine vs controls with no history of
      severe headache, using prospective data and validated diagnostic assessment. To
      examine the specificity of the migraine-suicide attempt risk by comparing it to
      the risk associated with non-migraine headache of comparable severity and
      disability. METHODS: A cohort of persons with migraine (n = 496), non-migraine
      severe headaches (n = 151), and controls with no history of severe headache (n =
      539) was randomly selected from the general community, assessed in 1997 and
      reassessed 2 years later. RESULTS: Persons with migraine had an increased risk of
      suicide attempt during the 2-year follow-up period, compared with controls. Odds
      ratio, adjusted for sex, psychiatric disorder, and previous history of suicide
      attempt at baseline was 4.43 (95% confidence interval [CI] 1.93, 10.2). Persons
      with non-migraine headache of comparable intensity and disability also had an
      increased risk of suicide attempt, compared to controls: odds ratio, adjusted for
      the same covariates, was 6.20 (95% CI 2.40, 16.0). The difference between the 2
      estimates was not significant. In the entire sample, headache severity at
      baseline predicted suicide attempt: a difference of 1 standard deviation (SD) in
      pain score increased the risk of suicide attempt by 79%, adjusting for sex and
      psychiatric disorders. CONCLUSIONS: The results suggest the possibility that pain
      severity might account in part for the increased risk of suicide attempt
      associated with migraine.

PMID- 22404177
TI  - Pharmacological profile of phosphatidylinositol 3-kinases and related
      phosphatidylinositols mediating endothelin(A)  receptor-operated native TRPC
      channels in rabbit coronary artery myocytes.
AB  - BACKGROUND AND PURPOSE: Endothelin(A) (ET(A) ) receptor-operated canonical
      transient receptor potential (TRPC) channels mediate Ca2+ influx pathways, which
      are important in coronary artery function. Biochemical pathways linking ET(A)
      receptor stimulation to TRPC channel opening are unknown. We investigated the
      involvement of phosphatidylinositol 3-kinases (PI3K) in ET(A) receptor activation
      of native heteromeric TRPC1/C5/C6 and TRPC3/C7 channels in rabbit coronary artery
      vascular smooth muscle cells (VSMCs). EXPERIMENTAL APPROACH: A pharmacological
      profile of PI3K was created by studying the effect of pan-PI3K, pan-Class I PI3K
      and Class I PI3K isoform-selective inhibitors on ET(A) receptor-evoked single
      TRPC1/C5/C6 and TRPC3/C7 channel activities in cell-attached patches from rabbit
      freshly isolated coronary artery VSMCs. The action of phosphatidylinositol 3
      phosphate- [PI(3)P], 4-phosphate- [PI(4)P] and 5-phosphate- [PI(5)P] containing
      molecules involved in PI3K-mediated reactions were studied in inside-out patches.
      Expression of PI3K family members in coronary artery tissue lysates were analysed
      using quantitative PCR. KEY RESULTS: ET(A) receptor-operated TRPC1/C5/C6 and
      TRPC3/C7 channel activities were inhibited by wortmannin. However, ZSTK474 and
      AS252424 reduced ET(A) receptor-evoked TRPC1/C5/C6 channel activity but
      potentiated TRPC3/C7 channel activity. All the PI(3)P-, PI(4)P- and PI(5)P
      containing molecules tested induced TRPC1/C5/C6 channel activation, whereas only
      PI(3)P stimulated TRPC3/C7 channels. CONCLUSIONS AND IMPLICATIONS: ET(A) receptor
      operated native TRPC1/C5/C6 and TRPC3/C7 channel activities are likely to be
      mediated by Class I PI3Kgamma and Class II/III PI3K isoforms, respectively. ET(A)
      receptor-evoked and constitutively active PI3Kgamma-mediated pathways inhibit
      TRPC3/C7 channel activation. PI3K-mediated pathways are novel regulators of
      native TRPC channels in VSMCs, and these signalling cascades are potential
      pharmacological targets for coronary artery disease.

PMID- 22404178
TI  - Understanding the relationship between photolysis efficiency and metal binding
      using ArgenCast photocages.
AB  - ArgenCast-1 (1), a photocage for silver utilizing acyclic polythioether 3,6,12,15
      tetrathia-9-azaheptadecane receptor and 4,5-dimethoxy-2-nitrobenzyl (DMNB)
      chromophore has been prepared using trimethylsilyl trifluoromethanesulfonate
      assisted electrophilic aromatic substitution. Metal binding studies with
      ArgenCast-1 reveal interactions with Ag(+), Hg(2+) and Cu(+), but only Ag(+)
      coordinates in both aqueous and organic solvents. The uncaging mechanism of
      ArgenCast-1 metal complex involves a photoreaction that converts the
      nitrobenzydrol into the electron withdrawing nitrosobenzophenone that
      participates in a resonance interaction with a metal-bound aniline nitrogen atom.
      The structural change following photolysis decreases availability of the nitrogen
      lone pair for Ag(+) coordination, but strong interactions between Ag(+) and the
      thioether ligands mitigates metal ion release. A resonance interaction with a key
      aci-nitro intermediate reduces the photolysis quantum yield of ArgenCast-1, so
      several naphthyl-based nitrobenzyl groups were screened as alternatives to DMNB.
      The naphthyl Ag(+) photocages, ArgenCast-2 and -3, exhibit nearly identical
      quantum yield to ArgenCast-1 owing to the dominance of resonance between aci
      nitro intermediate and the aniline nitrogen atom.

PMID- 22404179
TI  - Screening for leaf-associated endophytes in the genus Psychotria (Rubiaceae).
AB  - Burkholderia endophytes were identified within the leaves of non-nodulated
      members of the genus Psychotria. In contrast to leaf-nodulated Psychotria
      species, which are known to accommodate their endosymbionts into specialized
      endosymbiont-housing structures, non-nodulated species lack bacterial leaf
      nodules and harbor endosymbionts intercellularly between mesophyll cells. Based
      on molecular data (rps16, trnG, and trnLF), the phylogenetic reconstruction of
      the host plants revealed a separate origin of leaf-nodulated and non-nodulated
      Psychotria species. Despite a distinct phylogenetic position of the two host
      clades, the endophytes of the non-nodulated plants were not placed into a single
      monophyletic group but were found to be closely related to the leaf-nodulated
      endosymbionts. The observation of genetically similar endophytes in both
      nodulated and non-nodulated Psychotria lineages suggests that the host plant is
      playing a crucial role in the induction of leaf nodule formation. Moreover, the
      concentration of endosymbionts into specialized leaf nodules may be considered as
      a more derived evolutionary adaptation of the host plant, serving as an interface
      structure to facilitate metabolic exchange between plant and endosymbiont.

PMID- 22404180
TI  - Effect of the menstrual cycle phase on post-operative pain perception and
      analgesic requirements.
AB  - BACKGROUND: Research has shown that menstrual cycle phase may affect pain
      sensitivity. There is a lack of studies evaluating this effect on post-operative
      pain and analgesic needs. METHODS: In this prospective cohort study, we
      determined the effect of menstrual cycle phase on pain perception and analgesic
      requirements following total abdominal hysterectomy. Sixty women with regular
      menstrual cycles undergoing elective surgery were recruited and divided into
      'follicular' and 'luteal' groups according to their menstrual history. Post
      operative pain was managed with intravenous patient-controlled analgesia using
      tramadol. Intravenous morphine was used for rescue analgesia, and pain was
      assessed for 24 h. RESULTS: Pain scores in the recovery room and ward six and 24
      h post-operatively were similar in the groups at rest and on coughing. Pain
      scores at rest 12 h post-operatively were significantly higher in the luteal
      group (P = 0.043), while they were similar on coughing. There was no significant
      difference in the total tramadol requirement. Number of patients requiring rescue
      analgesia and the amount of morphine used was also similar. CONCLUSION: There was
      no difference in pain scores or analgesic requirements between the two groups
      except for rest pain at 12 h, which was significantly higher in the luteal group.
      As pain was assessed at 13 different time points, a significant difference seen
      only at one point could be due to random chance. We suggest that future research
      should concentrate on studying this issue in patients of relatively younger age
      groups with more pronounced hormonal variations during the cycle.

PMID- 22404183
TI  - New-generation free trade agreements threaten progressive tobacco and alcohol
      policies.

PMID- 22404182
TI  - Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan
      refractory myeloma: a randomized study.
AB  - OBJECTIVES: Thalidomide and bortezomib have been frequently used for second-line
      therapy in patients with myeloma relapsing after or refractory to initial
      melphalan-based treatment, but no randomized trials have been published comparing
      these two treatment alternatives. METHODS: Thalidomide- and bortezomib-naive
      patients with melphalan refractory myeloma were randomly assigned to low-dose
      thalidomide + dexamethasone (Thal-Dex) or bortezomib + dexamethasone (Bort-Dex).
      At progression on either therapy, the patients were offered crossover to the
      alternative drug combination. An estimated 300 patients would be needed for the
      trial to detect a 50% difference in median PFS between the treatment arms.
      RESULTS: After inclusion of 131 patients, the trial was prematurely closed
      because of low accrual. Sixty-seven patients were randomized to Thal-Dex and 64
      to Bort-Dex. Progression-free survival was similar (median, 9.0 months for Thal
      Dex and 7.2 for Bort-Dex). Response rate was similar (55% for Thal-Dex and 63%
      for Bort-Dex), but time to response was shorter (P < 0.05) and the VGPR rate
      higher (P < 0.01) for Bort-Dex. Time-to-other treatment after crossover was
      similar (median, 13.2 months for Thal-Dex and 11.2 months for Bort-Dex), as was
      overall survival (22.8 months for Thal-Dex and 19.0 for Bort-Dex). Venous
      thromboembolism was seen in seven patients and cerebrovascular events in four
      patients in the Thal-Dex group. Severe neuropathy, reactivation of herpes virus
      infections, and mental depression were more frequently observed in the Bort-Dex
      group. In the quality-of-life analysis, no difference was noted for physical
      function, pain, and global quality of life. Fatigue and sleep disturbances were
      significantly more prevalent in the Bort-Dex group. CONCLUSIONS: Thalidomide (50
      100 mg daily) in combination with dexamethasone seems to have an efficacy
      comparable with that of bortezomib and dexamethasone in melphalan refractory
      myeloma. However, the statistical strength of the results in this study is
      limited by the low number of included patients.

PMID- 22404184
TI  - The effect of baclofen on nocturnal gastroesophageal reflux and measures of sleep
      quality: a randomized, cross-over trial.
AB  - BACKGROUND: Baclofen, a GABA(b) agonist, has been shown to reduce episodes of
      gastroesophageal reflux (GER). To determine if baclofen would significantly
      reduce reflux during sleep, and also improve objective and subjective measures of
      sleep. METHODS: Twenty-one individuals with complaints of nighttime heartburn at
      least twice a week and a Carlsson GERD score of at least 5 were studied. Patients
      underwent polysomnography (PSG) and simultaneous esophageal pH monitoring on two
      occasions separated by approximately 1 week in a cross-over design. The night of
      each polysomnographic study, patients consumed a refluxogenic meal. Baclofen (40
      mg) or placebo was given in random order 90 min prior to the start of the PSG.
      KEY RESULTS: Baclofen significantly reduced the number of reflux events compared
      with placebo. Upright and recumbent acid contact times were both reduced by
      baclofen vs placebo, but the differences were not significant. Regarding sleep
      outcomes, several variables were significantly improved by baclofen. Total sleep
      time and sleep efficiency increased, and wake after sleep onset decreased in the
      baclofen condition compared with placebo. Proportion of Stage 1 sleep was also
      significantly decreased on baclofen. CONCLUSIONS & INFERENCES: In addition to
      reducing the number of reflux events during sleep, baclofen significantly
      improved several measures of sleep in patients with documented GER and sleep
      disturbances. Baclofen could therefore be considered as a useful adjunct therapy
      to proton pump inhibitors (PPIs) in patients with nighttime heartburn and sleep
      disturbance who continue to have heartburn and/or sleep complaints despite PPI
      therapy.

PMID- 22404185
TI  - Patients with ankylosing spondylitis have evidence of left ventricular
      asynchrony.
AB  - OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory disease that
      often leads to cardiovascular complications including aortic regurgitation and
      conduction disturbances. Left ventricular (LV) systolic asynchrony is defined as
      loss of the simultaneous peak contraction of corresponding cardiac segments. The
      aim of this study was to evaluate LV systolic asynchrony noninvasively in
      patients with AS by using tissue synchrony imaging (TSI). METHODS: Asynchrony was
      evaluated in 77 AS patients (61 male, mean age 36.4 +/- 10 years) and 40 controls
      (35 male, mean age 39.1 +/- 8.2 years). All study population underwent a
      comprehensive echocardiographic evaluation including TSI. The time to regional
      peak systolic velocity (Ts) during the ejection phase in LV was measured from TSI
      images by the six-basal and six-midsegmental model, and four TSI parameters of
      systolic asynchrony were computed. RESULTS: The baseline demographic and
      echocardiographic characteristics were similar between the patients enrolled and
      controls. All TSI parameters of LV asynchrony were prolonged in patients with AS
      compared to controls: the standard deviation (SD) of the 12 LV segments Ts (39.6
      +/- 19.6 vs. 24.7 +/- 11.6, P < 0.001); the maximal difference in Ts between any
      2 of the 12 LV segments (122.1 +/- 52.9 vs. 82.2 +/- 38.6, P < 0.001); the SD of
      the six basal LV segments (33.5 +/- 20.2 vs. 23 +/- 13.3, P = 0.008); and the
      maximal difference in Ts between any two of the six basal LV segments (84.6 +/-
      48.1 vs. 60.4 +/- 34.6, P = 0.008). The asynchrony parameters were significantly
      correlated with index of myocardial performance (Tei index) and peak systolic
      mitral annular velocity. CONCLUSION: TSI showed presence of LV systolic
      asynchrony in patients with AS which may account for the cardiovascular
      complications of AS.

PMID- 22404186
TI  - Cutaneous Rhodotorula treated with photodynamic therapy.

PMID- 22404187
TI  - Safety profile of enantiomers vs. racemic mixtures: it's the same?
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The physicochemical properties of
      racemates and stereoisomers of medicines can differ significantly, and this may
      affect the side-effect profile in addition to the pharmacokinetics and intended
      pharmacology. WHAT THIS STUDY ADDS: This is a study to investigate the profile of
      adverse drug reactions of racemic and enantiomeric forms of drugs. Our data
      suggest differences in the safety profile for ofloxacin and omeprazole. This area
      requires more work to investigate this for other compounds. AIMS: The objective
      was to investigate the safety profile of four drugs marketed as racemic and
      enantiomeric forms in France. METHODS: Data from the French PharmacoVigilance
      Data Base (January 2005 to June 2010) were analysed for four pairs of
      racemic/isomeric drugs. A case-noncase approach was used to measure the
      disproportionality of combination between adverse drug reaction (ADR) and
      exposure to drug. RESULTS: No significant difference in the number of ADRs was
      observed between Rac-cetirizine/(R)-cetirizine or Rac-citalopram/(S)-citalopram
      pairs. (S)-Omeprazole induced more haematological effects than Rac-omeprazole.
      Rac-Ofloxacin induced more haematological, renal and neuropsychiatric ADRs than
      (S)-ofloxacin, whereas levofloxacin was associated with more reports of
      musculoskeletal ADRs. CONCLUSIONS: The profile of ADRs could differ for some
      drugs marketed as racemic and enantiomeric forms. Further studies would be
      necessary to confirm these data.

PMID- 22404188
TI  - Systematic study of fluorescein-functionalized macrophotoinitiators for
      colorimetric bioassays.
AB  - We report a systematic investigation of a set of photoreducible
      macrophotoinitiators for use in polymerization-based signal amplification. To
      test the dependence of photopolymerization responses on the number of
      photoinitiators localized per molecular recognition event, we gradually increased
      the number of photoinitiator molecules coupled to a constant scaffold
      macromolecule from an average of 7 per polymer to an average of 168 per polymer.
      To evaluate the capacity of the macrophotoinitiators to detect molecular
      recognition, we coupled neutravidin to these molecules to recognize biotin
      labeled DNA immobilized on biochip test surfaces. Fluorescein macroinitiators
      were found to be useful in detecting molecular recognition above a threshold
      number of initiators per polymer. Above this threshold, increasing the number of
      initiators per macroinitiator resulted in increased signal strength. These
      findings demonstrate the feasibility of increasing the number of photoreducible
      initiators per binding event beyond three, the number used in previous studies,
      that the initiation reaction remains limiting in the range we investigated, and
      that the number of initiators per binding event in this system has a clear impact
      on assay sensitivity and signal strength.

PMID- 22404189
TI  - Metal-organic frameworks for analytical chemistry: from sample collection to
      chromatographic separation.
AB  - In modern analytical chemistry researchers pursue novel materials to meet
      analytical challenges such as improvements in sensitivity, selectivity, and
      detection limit. Metal-organic frameworks (MOFs) are an emerging class of
      microporous materials, and their unusual properties such as high surface area,
      good thermal stability, uniform structured nanoscale cavities, and the
      availability of in-pore functionality and outer-surface modification are
      attractive for diverse analytical applications. This Account summarizes our
      research on the analytical applications of MOFs ranging from sampling to
      chromatographic separation.  MOFs have been either directly used or engineered to
      meet the demands of various analytical applications. Bulk MOFs with microsized
      crystals are convenient sorbents for direct application to in-field sampling and
      solid-phase extraction. Quartz tubes packed with MOF-5 have shown excellent
      stability, adsorption efficiency, and reproducibility for in-field sampling and
      trapping of atmospheric formaldehyde. The 2D copper(II) isonicotinate packed
      microcolumn has demonstrated large enhancement factors and good shape- and size
      selectivity when applied to on-line solid-phase extraction of polycyclic aromatic
      hydrocarbons in water samples. We have explored the molecular sieving effect of
      MOFs for the efficient enrichment of peptides with simultaneous exclusion of
      proteins from biological fluids. These results show promise for the future of
      MOFs in peptidomics research. Moreover, nanosized MOFs and engineered thin films
      of MOFs are promising materials as novel coatings for solid-phase
      microextraction. We have developed an in situ hydrothermal growth approach to
      fabricate thin films of MOF-199 on etched stainless steel wire for solid-phase
      microextraction of volatile benzene homologues with large enhancement factors and
      wide linearity.  Their high thermal stability and easy-to-engineer nanocrystals
      make MOFs attractive as new stationary phases to fabricate MOF-coated capillaries
      for high-resolution gas chromatography (GC). We have explored a dynamic coating
      approach to fabricate a MOF-coated capillary for the GC separation of important
      raw chemicals and persistent organic pollutants with high resolution and
      excellent selectivity. We have combined a MOF-coated fiber for solid-phase
      microextraction with a MOF-coated capillary for GC separation, which provides an
      effective MOF-based tandem molecular sieve platform for selective microextraction
      and high-resolution GC separation of target analytes in complex samples. 
      Microsized MOFs with good solvent stability are attractive stationary phases for
      high-performance liquid chromatography (HPLC). These materials have shown high
      resolution and good selectivity and reproducibility in both the normal-phase HPLC
      separation of fullerenes and substituted aromatics on MIL-101 packed columns and
      position isomers on a MIL-53(Al) packed column and the reversed-phase HPLC
      separation of a wide range of analytes from nonpolar to polar and acidic to basic
      solutes. Despite the above achievements, further exploration of MOFs in
      analytical chemistry is needed. Especially, analytical application-oriented
      engineering of MOFs is imperative for specific applications.

PMID- 22404191
TI  - Primary prevention of latex allergy in healthcare-spectrum of strategies
      including the European glove standardization.
AB  - IgE-mediated allergy to natural rubber latex was first noted from rubber gloves
      in 1979. The initial reports in dermatological journals described contact
      urticarial reactions; later, severe generalized allergic reactions and asthma
      were documented. A considerable proportion of the people involved in medical and
      dental care were found to be sensitized to latex. This article describes and
      surveys a broad range of primary prevention measures at the local and national
      levels. Examples are given from paediatrics, dental education, and medical care.
      National strategies and position papers on latex allergy are presented in which
      medical professionals, manufacturers and public authorities have cooperated.
      Special reference is paid to the European work to standardize medical gloves,
      which led to document EN 455:3.

PMID- 22404190
TI  - Searching for coordinated activity cliffs using particle swarm optimization.
AB  - Activity cliffs are formed by structurally similar compounds having large potency
      differences. Coordinated activity cliffs evolve when compounds within groups of
      structural neighbors form multiple cliffs with different partners, giving rise to
      local networks of cliffs in a data set. Using particle swarm optimization, a
      machine learning approach, we systematically searched for coordinated activity
      cliffs in different compound sets. Regardless of the global SAR characteristics
      of these data sets, coordinated activity cliffs introducing strong local SAR
      discontinuity were identified in most cases. Compound subsets forming coordinated
      activity cliffs represent centers of SAR discontinuity and have high SAR
      information content. Through particle swarm optimization guided by subset
      discontinuity scoring, compounds forming the largest coordinated activity cliffs
      can automatically be extracted from large compound data sets.

PMID- 22404193
TI  - 'Calibration' of our patch test reading technique is necessary.
AB  - BACKGROUND: Patch testing has been used for more than 100 years as the best means
      to diagnose contact allergy. The increased use of the technique makes
      standardization of the methodology most important. Progress in the
      standardization of the patch test technique has been made through guidelines.
      OBJECTIVES: To investigate the intra-individual and inter-individual differences
      in reading of patch tests in order to validate the actual patch test reading when
      reading is performed according to the same guidelines, and to determine whether
      information on guidelines actually improves the outcome of the patch test
      readings PATIENTS/MATERIALS/METHODS: A patch test course for dermatologists was
      performed. Volunteers were patch tested with irritants and allergens in different
      concentrations. The patch test reader did not know what substances had been
      tested. RESULTS: Irritant reactions/doubtful reactions and weak allergic
      reactions are difficult to differentiate (accordance for these reactions 21%,
      19%, and 44%). Information and education have a beneficial effect on results, as
      shown by an improved kappa value. CONCLUSIONS: Standardization of patch test
      reading is important. Information on the classification system resulted in a
      significant improvement. Interpretation of guidelines should be continuously
      evaluated.

PMID- 22404192
TI  - Stability of selected volatile contact allergens in different patch test chambers
      under different storage conditions.
AB  - BACKGROUND: Patch test preparations of volatile substances may evaporate during
      storage, thereby giving rise to reduced patch test concentrations. OBJECTIVES: To
      investigate the stability of selected acrylates/methacrylates and fragrance
      allergens in three different test chambers under different storage conditions.
      METHODS: Petrolatum samples of methyl methacrylate (MMA), 2-hydroxyethyl
      methacrylate (2-HEMA), 2-hydroxypropyl acrylate (2-HPA), cinnamal and eugenol in
      patch test concentrations were stored in three different test chambers (IQ
      chamberTM, IQ UltimateTM, and Van der Bend(r) transport container) at room
      temperature and in a refrigerator. The samples were analysed in triplicate with
      high-performance liquid chromatography. RESULTS: The decrease in concentration
      was substantial for all five allergens under both storage conditions in IQ
      chamberTM and IQ UltimateTM, with the exception of 2-HEMA during storage in the
      refrigerator. For these two chamber systems, the contact allergen concentration
      dropped below the stability limit in the following order: MMA, cinnamal, 2-HPA,
      eugenol, and 2-HEMA. In the Van der Bend(r) transport container, the contact
      allergens exhibited acceptable stability under both storage conditions, whereas
      MMA and 2-HPA required cool storage for maintenance of the limit. CONCLUSION: The
      Van der Bend(r) transport container was the best device for storage of samples of
      volatile contact allergens.

PMID- 22404194
TI  - The effectiveness of integrated care for patients with hand eczema: results of a
      randomized, controlled trial.
AB  - OBJECTIVES: To evaluate the effectiveness of integrated, multidisciplinary care
      as compared with usual care for patients with moderate to severe, chronic hand
      eczema after 26 weeks of follow-up. BACKGROUND: This study was designed as a
      randomized, controlled trial. METHODS: Patients who visited one of the
      participating hospitals were randomized to integrated care or usual care.
      Integrated care was carried out by a multidisciplinary team, and integrated
      clinical and occupational care to optimize treatment, and the patient's quality
      of life and social functioning. Outcome variables were clinical assessment of
      hand eczema with the Hand Eczema Severity Index (HECSI) (primary outcome),
      quality of life, patient's global assessment of hand eczema, and sick leave.
      RESULTS: Average improvement on the HECSI was 22.4 points in the intervention
      group and 11.7 points in the control group. The mean difference in improvement on
      the HECSI between both groups after 26 weeks was 10.7 points in favour of the
      integrated care group (standard error 5.3, 95% confidence interval 0.3-21.1, p =
      0.044). No differences in improvement between the groups were found for any of
      the other outcomes. CONCLUSIONS: The integrated care programme significantly
      improved clinical outcome measures as compared with usual care, and was effective
      for treating patients with chronic hand eczema.

PMID- 22404195
TI  - Patch test practices and perceptions of Chinese dermatologists: results of a
      cross-sectional survey.
AB  - BACKGROUND: Patch testing is the most valuable tool for diagnosing allergic
      contact dermatitis. Whereas previous surveys have evaluated patch test practices
      and perceptions of dermatologists worldwide, no such information is available
      relating to Chinese dermatologists. OBJECTIVES: We surveyed Chinese
      dermatologists by using questionnaires to investigate their patch test practices
      and the prevalence of patch testing. METHODS: A cross-sectional survey of Chinese
      dermatologists was conducted at the National Congress of Dermatology in December
      2006. RESULTS: Of the 1116 questionnaires distributed, 1089 (97.6%) were
      returned. Eighty-six per cent of dermatologists reported performing patch
      testing. Dermatologists from regional hospitals were significantly more likely to
      perform patch testing (p < 0.001). The majority (80.8%) used the baseline
      (standard) allergen series made in China. Eighty-seven per cent of testers
      performed only a single patch test reading. The dermatologists' perceptions of
      the patch test indicated that 43.1% of the respondents thought that patch testing
      could be used to diagnose irritant contact dermatitis, and only 30.3% of the
      respondents made the correct choice when asked to read a patch test reaction.
      CONCLUSIONS: Patch testing is widespread among Chinese dermatologists, but
      further improvement and education regarding the procedure is required.

PMID- 22404196
TI  - No skin reactions to mineral powders in nickel-sensitive subjects.
AB  - BACKGROUND: Cosmetic products are known to be able to induce contact dermatitis.
      Contact dermatitis may also be induced by nickel, and it is estimated that up to
      17% of women are allergic to nickel. OBJECTIVES: The aim of the present study was
      to investigate whether nickel sensitized individuals react to make-up products
      containing pigments with nickel as an impurity. PATIENTS/MATERIALS/METHODS:
      Twenty-three individuals with a clinical history of nickel allergy and/or with
      positive patch test reactions to nickel were exposed to mineral make-up products
      and individual pigments dispersed in alkylbenzoate (50%) in small Finn
      Chambers(r) for 48 hr. The skin reactions were evaluated visually and with a non
      invasive instrument that quantifies skin erythema. RESULTS: The results showed
      that 74% of the included individuals showed a visible reaction to the positive
      control nickel sulfate, and a significant correlation was found between the
      visual and instrumental readings. However, none of the nickel sensitive
      individuals reacted to the test products. A subgroup analysis of the 50% most
      sensitive individuals also confirmed the absence of skin reactions to the
      powders. CONCLUSIONS: The bioavailability of the trace amounts of nickel in the
      particles was below the level needed to elicit an eczematous reaction in any of
      the nickel-sensitized individuals.

PMID- 22404197
TI  - How well is the outcome of patch testing remembered by the patients? A 10-year
      follow-up of testing with the Swedish baseline series at the Department of
      Dermatology in Orebro, Sweden.
AB  - BACKGROUND: Patch testing is beneficial for patients with contact dermatitis.
      However, it is not known how well the outcome of patch testing is remembered
      after a prolonged period. OBJECTIVES: To study how well patients remember the
      outcome of their tests after 1-10 years. PATIENTS/MATERIALS/METHODS: In 2010, a
      questionnaire was sent to all patients tested with the Swedish baseline series in
      2009, 2005, and 2000. RESULTS: The response rate was 53.3% (252/473), and 96%
      (241/252) of patients reported that they had been submitted for allergy testing.
      Among those with positive patch test results, 79% (111/141) remembered a positive
      result and 29% (41/141) reported the correct name of the allergen. We found a
      wide variation (0-80%) in how well the patients remembered positive test results
      for different allergens. The ability to recall allergens had no relationship with
      the localization or extension of eczema lesions, but was negatively correlated
      with the number of diagnosed allergies, the number of years after patch testing,
      and being male. CONCLUSIONS: Our results indicate that improved information for
      patients following patch testing is required, in order to improve the prognosis
      of contact dermatitis.

PMID- 22404198
TI  - Impact of tumour necrosis factor-alpha polymorphisms on irritant contact
      dermatitis.
AB  - BACKGROUND: Genetic variations in genes coding for cytokines involved in skin
      inflammation may alter their expression, thus changing the susceptibility to
      irritant contact dermatitis (ICD). OBJECTIVES: To determine the prevalence of
      polymorphisms in the cytokine genes TNFA-238 and TNFA-308 in patients with
      occupational ICD, and to compare it with that in controls. METHODS: In a case
      control study, 478 patients with occupational ICD of the hands were genotyped for
      TNFA-238 and TNFA-308 polymorphisms. The results were compared with those for 393
      apprentices from the same high-risk occupations (controls). RESULTS: For a
      carrier of a variant TNFA-238A allele, the odds ratio (OR) of acquiring ICD was
      0.57 [95% confidence interval (CI) 0.34-0.97], suggesting a protective effect of
      the A allele. The genotype distributions were 94.4% wild type (G/G), 5.6%
      heterozygous (G/A) and 0% homozygous for variant allele (A/A) in patients, and
      90.9%, 8.5%, and 0.6%, respectively in controls. In contrast, carriers of the
      variant TNFA-308A allele had an increased risk of ICD [OR 1.33; 95% CI 1.05-1.74;
      G/G 66.4%, G/A 31.2%, and A/A 2.4% (patients) versus 73.5%, 24.6%, 1.9% in
      controls]. CONCLUSIONS: Individuals with a TNFA-238 polymorphism are less prone
      and those with a TNFA-308 polymorphism are more prone to develop ICD of the
      hands, suggesting a protective versus a detrimental effect of the A allele
      respectively.

PMID- 22404199
TI  - Cobalt spot test used for diagnosis of occupationally-related exposure to cobalt
      containing powder.

PMID- 22404200
TI  - Contact allergy to di-isodecyl phthalate.

PMID- 22404201
TI  - Arabidopsis GCP3-interacting protein 1/MOZART 1 is an integral component of the
      gamma-tubulin-containing microtubule nucleating complex.
AB  - Microtubules in eukaryotic cells are nucleated from ring-shaped complexes that
      contain gamma-tubulin and a family of homologous gamma-tubulin complex proteins
      (GCPs), but the subunit composition of the complexes can vary among fungi,
      animals and plants. Arabidopsis GCP3-interacting protein 1 (GIP1), a small
      protein with no homology to the GCP family, interacts with GCP3 in vitro, and is
      a plant homolog of vertebrate mitotic-spindle organizing protein associated with
      a ring of gamma-tubulin 1 (MOZART1), a recently identified component of the gamma
      tubulin complex in human cell lines. In this study, we characterized two closely
      related Arabidopsis GIP1s: GIP1a and GIP1b. Single mutants of gip1a and gip1b
      were indistinguishable from wild-type plants, but their double mutant was
      embryonic lethal, and showed impaired development of male gametophytes.
      Functional fusions of GIP1a with green fluorescent protein (GFP) were used to
      purify GIP1a-containing complexes from Arabidopsis plants, which contained all
      the subunits (except NEDD1) previously identified in the Arabidopsis gamma
      tubulin complexes. GIP1a and GIP1b interacted specifically with Arabidopsis GCP3
      in yeast. GFP-GIP1a labeled mitotic microtubule arrays in a pattern largely
      consistent with, but partly distinct from, the localization of the gamma-tubulin
      complex containing GCP2 or GCP3 in planta. In interphase cortical arrays, the
      labeled complexes were preferentially recruited to existing microtubules, from
      which new microtubules were efficiently nucleated. However, in contrast to
      complexes labeled with tagged GCP2 or GCP3, their recruitment to cortical areas
      with no microtubules was rarely observed. These results indicate that
      GIP1/MOZART1 is an integral component of a subset of the Arabidopsis gamma
      tubulin complexes.

PMID- 22404202
TI  - Dissemination of ceftazidime-resistant Acinetobacter baumannii clonal complex 92
      in Korea.
AB  - AIMS: This study was performed to describe the epidemiological traits of
      ceftazidime-resistant Acinetobacter baumannii clinical isolates from Korea.
      METHODS AND RESULTS: Antimicrobial susceptibilities were determined by disk
      diffusion assay. PCR experiments were performed to detect genes encoding extended
      spectrum beta-lactamases and metallo-beta-lactamases. Detection of ISAba1
      upstream of the bla(ADC) gene was also performed by PCR amplification. The
      genetic organization of the bla(PER-1) gene was investigated by PCR mapping and
      sequencing of the regions surrounding the gene. Multilocus sequence typing was
      performed using seven housekeeping genes. A. baumannii isolates of clonal complex
      (CC) 92 exhibited a higher resistance rate (286/289, 99%) against ceftazidime
      compared to A. baumannii isolates of non-CC92 (7/87, 8%). Amongst 286 ceftazidime
      resistant isolates of CC92, 100 (35%) isolates carried the bla(PER-1) gene, while
      none of the 87 isolates of non-CC92 carried the gene. The bla(ADC) gene
      associated with an ISAba1 element was detected in 98% (281/286) of ceftazidime
      resistant isolates of CC92 and in all seven ceftazidime-resistant isolates of non
      CC92. The bla(PER-1) gene was located on a transposon, Tn1213 (ISPa12-bla(PER-1) 
      Deltagst-ISPa13), in 95 isolates and on a complex class 1 integron (orf513
      bla(PER-1) -putative ABC transporter gene) in five isolates. Southern blot
      experiments confirmed the chromosomal location of the bla(PER-1) gene.
      CONCLUSIONS: Acinetobacter baumannii CC92 which has acquired ceftazidime
      resistance by the production of PER-1 extended-spectrum beta-lactamases and/or
      the overproduction of Acinetobacter-derived cephalosporinase is widely
      disseminated in Korea. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows the
      mechanisms of acquiring ceftazidime resistance in A. baumannii and the
      epidemiological traits of ceftazidime-resistant A. baumannii isolates from Korea.

PMID- 22404203
TI  - Reactive molecular dynamics simulation of solid nitromethane impact on (010)
      surfaces induced and nonimpact thermal decomposition.
AB  - Which is the first step in the decomposition process of nitromethane is a
      controversial issue, proton dissociation or C-N bond scission. We applied
      reactive force field (ReaxFF) molecular dynamics to probe the initial
      decomposition mechanisms of nitromethane. By comparing the impact on (010)
      surfaces and without impact (only heating) for nitromethane simulations, we found
      that proton dissociation is the first step of the pyrolysis of nitromethane, and
      the C-N bond decomposes in the same time scale as in impact simulations, but in
      the nonimpact simulation, C-N bond dissociation takes place at a later time. At
      the end of these simulations, a large number of clusters are formed. By analyzing
      the trajectories, we discussed the role of the hydrogen bond in the initial
      process of nitromethane decompositions, the intermediates observed in the early
      time of the simulations, and the formation of clusters that consisted of C-N-C-N
      chain/ring structures.

PMID- 22404205
TI  - Important achievements in the search for psychopathological predictors, but still
      a long road ahead: editorial comment to Baldessarini RJ, Undurraga J, Vazquez GH
      et al. 'Predominant recurrence polarity among 928 adult international bipolar-I
      disorder patients' (3).

PMID- 22404206
TI  - Treatment of bipolarity + medical comorbidity = costability: an editorial comment
      to Magalhaes PV, Kapczinski F, Nierenberg AA, Deckersback T, Weisinger D, Dodd S,
      Berk M. Illness burden and medical comorbidity in the Systemic Treatment
      Enhancement Program for Bipolar Disorder (1).

PMID- 22404207
TI  - Social cognition and its potential role in bipolar disorder roughening: an
      editorial comment to Samame C, Matino DJ, Strejilevich S. 'Social cognition in
      euthymic bipolar disorder: systematic review and meta-analytic approach' (1).

PMID- 22404208
TI  - Reverse shape selectivity in the liquid-phase adsorption of xylene isomers in
      zirconium terephthalate MOF UiO-66.
AB  - Powder, agglomerates, and tablets of the microporous zirconium(IV) terephthalate
      metal-organic framework UiO-66 were evaluated for the selective adsorption and
      separation of xylene isomers in the liquid phase using n-heptane as the eluent.
      Pulse experiments, performed at 313 K in the presence of n-heptane, revealed the
      o-xylene preference of this material, which was further confirmed by binary and
      multicomponent breakthrough experiments in the presence of m- and p-xylene,
      resulting in selectivities at 313 K of 1.8 and 2.4 with regards to m-xylene and p
      xylene, respectively. Additionally, because p-xylene is the less retained isomer,
      UiO-66 presents a selectivity pattern that is reverse of that of the xylenes'
      molecular dimension with respect to shape selectivity. The shaping of the
      material as tablets did not significantly change its selectivity toward the o
      xylene isomer or toward p-xylene, which was the less retained isomer, despite a
      loss in capacity. Finally, the selectivity behavior of UiO-66 in the liquid n
      heptane phase makes it a suitable material for o-xylene separation in the extract
      (heavy product) or p-xylene separation in the raffinate (light product) by
      simulated moving bed technology.

PMID- 22404209
TI  - The Loneliness Questionnaire-Short Version: an evaluation of reverse-worded and
      non-reverse-worded items via item response theory.
AB  - Although reverse-worded items have often been incorporated in scale construction
      to minimize the effects of acquiescent reporting biases, some researchers have
      more recently begun questioning this approach and wondering whether the
      advantages associated with incorporating reverse-worded items is worth the
      complexities that they bring to measures (e.g., Brown,  2003 ; Marsh,  1996 ). In
      this study, we used item response theory (IRT) to determine whether there is
      statistical justification to eliminate the reverse-worded items (e.g., "I have
      lots of friends") from the Loneliness Questionnaire (LQ; Asher, Hymel, & Renshaw,
      1984) and retain only the non-reverse-worded items (e.g., "I'm lonely") to inform
      the provision of a shortened LQ version. Using a large sample of children (Grades
      2-7; n = 6,784) and adolescents (Grades 8-12; n = 4,941), we examined the
      psychometric properties of the 24-item LQ and found support for retaining the 9
      non-reverse-worded LQ items to make up a shortened measure of loneliness in
      youth. We found that the non-reverse-worded items were associated with superior
      psychometric properties relative to the reverse-worded items with respect to
      reliability and IRT parameters (e.g., discrimination and item information). A 3
      point Likert-type scale was also found to be more suitable for measuring
      loneliness across both children and adolescents compared to the original 5-point
      scale. The relative contributions of reverse-worded and non-reverse-worded items
      in scale development for youth instruments are also discussed.

PMID- 22404210
TI  - Presentation and outcome of post-traumatic benign paroxysmal positional vertigo.
AB  - CONCLUSION: The clinical presentation and outcome of post-traumatic benign
      paroxysmal positional vertigo (t-BPPV) are different from those idiopathic BPPV
      (i-BPPV). It appears that t-BPPV is more difficult to treat than i-BPPV.
      OBJECTIVE: To identify the clinical presentation and outcome of t-BPPV. METHODS:
      We reviewed the medical records of 40 patients with BPPV after head injury during
      the period 2004-2011. The outcome was compared with the outcome of 46 patients
      with i-BPPV who were treated over the same period. RESULTS: In all, 55% of
      patients with t-BPPV had involvement of two or more semicircular canals (SCCs) in
      comparison with 6.5% of patients with i-BPPV (p < 0.01). Also, 25% of patients
      with t-BPPV had involvement of bilateral SCCs in comparison with 2% of patients
      with i-BPPV (p < 0.01). We found that 35% of patients with t-BPPV were free of
      the symptoms and signs after a single physical repositioning maneuver, in
      comparison with 84% of patients with i-BPPV (p < 0.001). During a 1-year follow
      up, 67% of patients with t-BPPV and 12% of patients with i-BPPV had a recurrent
      attack (p < 0.001).

PMID- 22404212
TI  - Antimicrobial photodynamic therapy on drug-resistant Pseudomonas aeruginosa
      induced infection. An in vivo study.
AB  - Pseudomonas aeruginosa is considered one of the most important pathogens that
      represent life-threatening risk in nosocomial environments, mainly in patients
      with severe burns. Antimicrobial photodynamic therapy (aPDT) has been effective
      to kill bacteria. The purpose of this study was to develop a burn wound and
      bloodstream infection model and verify aPDT effects on it. In vitro, we tested
      two wavelengths (blue and red LEDs) on a clinical isolate of P. aeruginosa strain
      with resistance to multiple antibiotics using HB:La(+3)  as photosensitizer.
      Verapamil((r))  associated to aPDT was also studied. In vivo, P. aeruginosa
      infected burned mice were submitted to aPDT. Bacterial counting was performed on
      local infection and bloodstream. Survival time of animals was also monitored. In
      this study, aPDT was effective to reduce P. aeruginosa in vitro. In addition,
      Verapamil((r))  assay showed that HB:La(+3)  is not recognized by ATP-binding
      cassete (ABC) efflux pump mechanism. In the in vivo study, aPDT was able to
      reduce bacterial load in burn wounds, delay bacteremia and keep the bacterial
      levels in blood 2-3 logs lower compared with an untreated group. Mice survival
      was increased on 24 h. Thus, this result suggests that aPDT may also be a novel
      prophylactic treatment in the care of burned patients.

PMID- 22404211
TI  - Early non-invasive ventilation treatment for severe influenza pneumonia.
AB  - The role of non-invasive ventilation (NIV) in acute respiratory failure caused by
      viral pneumonia remains controversial. Our objective was to evaluate the use of
      NIV in a cohort of (H1N1)v pneumonia. Usefulness and success of NIV were assessed
      in a prospective, observational registry of patients with influenza A (H1N1)
      virus pneumonia in 148 Spanish intensive care units (ICUs) in 2009-10.
      Significant variables for NIV success were included in a multivariate analysis.
      In all, 685 patients with confirmed influenza A (H1N1)v viral pneumonia were
      admitted to participating ICUs; 489 were ventilated, 177 with NIV. The NIV was
      successful in 72 patients (40.7%), the rest required intubation. Low Acute
      Physiology and Chronic Health Evaluation (APACHE) II, low Sequential Organ
      Failure Assessment (SOFA) and absence of renal failure were associated with NIV
      success. Success of NIV was independently associated with fewer than two chest X
      ray quadrant opacities (OR 3.5) and no vasopressor requirement (OR 8.1). However,
      among patients with two or more quadrant opacities, a SOFA score <=7 presented a
      higher success rate than those with SOFA score >7 (OR 10.7). Patients in whom NIV
      was successful required shorter ventilation time, shorter ICU stay and hospital
      stay than NIV failure. In patients in whom NIV failed, the delay in intubation
      did not increase mortality (26.5% versus 24.2%). Clinicians used NIV in 25.8% of
      influenza A (H1N1)v viral pneumonia admitted to ICU, and treatment was effective
      in 40.6% of them. NIV success was associated with shorter hospital stay and
      mortality similar to non-ventilated patients. NIV failure was associated with a
      mortality similar to those who were intubated from the start.

PMID- 22404218
TI  - Sulfasalazine for brain cancer fits.
AB  - Recent research has identified an important role for a cystine-glutamate
      antiporter (system Xc) in the biology of malignant brain tumors. This transporter
      is effectively inhibited by sulfasalazine, a drug widely used to treat a number
      of chronic inflammatory conditions such as Crohn's disease. Preclinical data show
      that sulfasalazine is an effective inhibitor of tumor growth and tumor-associated
      seizures. These studies suggest that the cystine-glutamate antiporter is a
      valuable drug target for which tumor-specific drugs can be generated. In the
      meantime, sulfasalazine may be considered as adjuvant treatment for malignant
      gliomas.

PMID- 22404213
TI  - Identification of cellular proteins required for replication of human
      immunodeficiency virus type 1.
AB  - Cellular proteins are essential for human immunodeficiency virus type 1 (HIV-1)
      replication and may serve as viable new targets for treating infection. Using
      gene trap insertional mutagenesis, a high-throughput approach based on random
      inactivation of cellular genes, candidate genes were found that limit virus
      replication when mutated. Disrupted genes (N=87) conferring resistance to lytic
      infection with several viruses were queried for an affect on HIV-1 replication by
      utilizing small interfering RNA (siRNA) screens in TZM-bl cells. Several genes
      regulating diverse pathways were found to be required for HIV-1 replication,
      including DHX8, DNAJA1, GTF2E1, GTF2E2, HAP1, KALRN, UBA3, UBE2E3, and VMP1.
      Candidate genes were independently tested in primary human macrophages, toxicity
      assays, and/or Tat-dependent beta-galactosidase reporter assays. Bioinformatics
      analyses indicated that several host factors present in this study participate in
      canonical pathways and functional processes implicated in prior genome-wide
      studies. However, the genes presented in this study did not share identity with
      those found previously. Novel antiviral targets identified in this study should
      open new avenues for mechanistic investigation.

PMID- 22404217
TI  - Submaximal PPARgamma activation and endothelial dysfunction: new perspectives for
      the management of cardiovascular disorders.
AB  - PPARgamma activation plays an important role in glucose metabolism by enhancing
      insulin sensitization. PPARgamma is a primary target for thiazolidinedione
      structured insulin sensitizers like pioglitazone and rosiglitazone employed for
      the treatment of type 2 diabetes mellitus. Additionally, PPARgamma activation
      inhibits adhesion cascades and detrimental vascular inflammatory events.
      Importantly, activation of PPARgamma plays a distinctive role in regulating the
      physiology and expression of endothelial nitric oxide synthase (eNOS) in the
      endothelium, resulting in enhanced generation of vascular nitric oxide. The
      PPARgamma activation-mediated vascular anti-inflammatory and direct endothelial
      functional regulatory actions could, therefore, be beneficial in improving the
      vascular function in patients with atherosclerosis and hypertension with or
      without diabetes mellitus. Despite the disappointing cardiac side effect profile
      of rosiglitazone-like PPARgamma full agonists, the therapeutic potential of novel
      pharmacological agents targeting PPARgamma submaximally cannot be ruled out. This
      review discusses the potential regulatory role of PPARgamma on eNOS expression
      and activation in improving the function of vascular endothelium. We argue that
      partial/submaximal activation of PPARgamma could be a major target for vascular
      endothelial functional improvement. Interestingly, newly synthesized partial
      agonists of PPARgamma such as balaglitazone, MBX-102, MK-0533, PAR-1622, PAM
      1616, KR-62776 and SPPARgammaM5 are devoid of or have a reduced tendency to cause
      the adverse effects associated with full agonists of PPARgamma. We propose that
      the vascular protective properties of pharmacological agents, which submaximally
      activate PPARgamma, should be investigated. Moreover, the therapeutic
      opportunities of agents that submaximally activate PPARgamma in preventing
      vascular endothelial dysfunction (VED) and VED-associated cardiovascular
      disorders are discussed.

PMID- 22404219
TI  - Effects of propofol with hyperthermia in a rat model of endotoxemic shock.
AB  - BACKGROUND: We aimed to investigate the effects of active mild hyperthermia and
      the effects of active mild hyperthermia with propofol on mortality and
      inflammatory responses during endotoxin-induced shock in rats. METHODS:
      Intravenous Escherichia coli endotoxin (15 mg/kg over 2 min) was injected in 48
      rats. The animals were randomly allocated to one of the following four groups (n
      = 12 per group): normothermia group (group N), rectal temperature maintained
      between 36  degrees C and 38  degrees C; hyperthermia group (group H), rectal
      temperature was moderate and maintained between 39  degrees C and 40  degrees C;
      propofol with normothermia group (group PN), propofol (10 mg/kg/h) was
      administered, and temperature was between 36  degrees C and 38  degrees C;
      Propofol with hyperthermia group (group PH), propofol (10 mg/kg/h) administrated,
      and temperatures were maintained between 39  degrees C and 40  degrees C. The
      primary outcome was mortality 8 h after endotoxin injection. Secondary outcomes
      included changes in haemodynamics, arterial blood gases and plasma cytokine
      concentrations for the 8-h observation period. RESULTS: Mortality rates 8 h after
      endotoxin injection were 92%, 100%, 68% and 50% for N, H, PN and PH groups,
      respectively. There was no difference in hypotension, acidosis, and increase in
      plasma cytokine concentrations between N and H groups, but these parameters were
      attenuated in group PH. CONCLUSION: The mortality rates in the present study were
      extremely high; further hypotension and elevations in plasma pro-inflammatory and
      anti-inflammatory cytokine concentrations after endotoxin injection were not
      attenuated by mild hyperthermia between 39  degrees C and 40  degrees C, but they
      were attenuated by propofol with mild hyperthermia.

PMID- 22404220
TI  - T-type calcium channel blockade improves survival and cardiovascular function in
      thalassemic mice.
AB  - OBJECTIVES: Iron-overload cardiomyopathy is a major cause of morbidity and
      mortality in patients with thalassemia. However, the precise mechanisms of iron
      entry and sequestration in the heart are still unclear. Our previous study showed
      that Fe(2+) uptake in thalassemic cardiomyocytes are mainly mediated by T-type
      calcium channels (TTCC). Nevertheless, the role of TTCC as well as other
      transporters such as divalent metal transporter1 (DMT1) and L-type calcium
      channels (LTCC) as possible portals for iron entry into the heart in in vivo
      thalassemic mice under an iron-overload condition has not been investigated.
      METHODS: An iron-overload condition was induced in genetically altered beta
      thalassemic mice and adult wild-type mice by feeding them with an iron diet (0.2%
      ferrocene w/w) for 3 months. Then, blockers for LTCC (verapamil and nifedipine),
      TTCC (efonidipine), and DMT1 (ebselen) as well as iron chelator desferoxamine
      (DFO) were given for 1 month with continuous iron feeding. RESULTS: Treatment
      with LTCC, TTCC, DMT1 blockers, and DFO reduced cardiac iron deposit, cardiac
      malondialdehyde (MDA), plasma non-transferrin-bound iron, and improved heart rate
      variability and left ventricular (LV) function in thalassemic mice with iron
      overload. Only TTCC and DMT1 blockers and DFO reduced liver iron accumulation,
      liver MDA, plasma MDA, and decreased mortality rate in iron-overloaded
      thalassemic mice. CONCLUSIONS: DMT1, LTCC, and TTCC played important roles for
      iron entry in the thalassemic heart under an iron-overloaded condition. Unlike
      LTCC blocker, TTCC blocker provided all benefits including attenuating iron
      deposit in both the heart and liver, reduced oxidative stress, and decreased
      mortality in iron-overloaded mice.

PMID- 22404221
TI  - Interventions to improve the oral feeding performance of preterm infants.
AB  - AIM: Preterm infants have difficulty oral feeding. We hypothesized that a
      specific sucking and swallowing exercises vs. no intervention accelerate the
      attainment of independent oral feeding through a faster maturation of infants'
      oral feeding skills (OFS). METHODS: Very low birthweight infants were randomized
      to a control, sucking and swallowing groups. Sucking consisted of active sucking
      on a pacifier, and swallowing of placing a milk bolus (0.05-0.2 mL) on the tongue
      where the bolus rests prior to entering the pharynx. Primary outcome was days
      from start to independent oral feeding (SOF-IOF). Secondary outcomes included
      overall transfer (OT, % volume taken/volume prescribed), proficiency (PRO, %
      volume taken at 5 min/volume prescribed), rate of transfer (RT, mL/min) over the
      entire feeding and infants' OFS levels. OFS levels were defined by PRO and RT.
      RESULTS: Days from SOF to IOF vs controls (21 +/- 2) were similar for the sucking
      group (19 +/- 2) and shorter for the swallowing group (15 +/- 2; p = 0.019). Only
      the latter infants demonstrated more mature OFS levels than controls. CONCLUSION:
      The swallowing exercise is an efficacious intervention in facilitating the
      attainment of independent oral feeding, but not the sucking exercise. We
      speculate that the swallowing benefit resulted from an accelerated maturation of
      infants' OFS levels.

PMID- 22404222
TI  - Microbes and the gut-brain axis.
AB  - BACKGROUND: The 'gut-brain' or 'brain-gut axis', depending on whether we
      emphasize bottom-up or top-bottom pathways, is a bi-directional communication
      system, comprised of neural pathways, such as the enteric nervous system (ENS),
      vagus, sympathetic and spinal nerves, and humoral pathways, which include
      cytokines, hormones, and neuropeptides as signaling molecules. Recent evidence,
      mainly arising from animal models, supports a role of microbes as signaling
      components in the gut-brain axis. AIMS: The purpose of this review is to
      summarize our current knowledge regarding the role of microbes, including
      commensals, probiotics and gastrointestinal pathogens, in bottom-up pathways of
      communication in the gut-brain axis. Although this has clear implications for
      psychiatric co-morbidity in functional and inflammatory conditions of the gut,
      the focus of this review will be to discuss the current evidence for a role of
      bacteria (commensals, probiotics, and pathogens) as key modulators of gut-brain
      communication. RESULTS & CONCLUSIONS: The strongest evidence for a role of
      microbes as signaling components in the gut-brain axis currently arises from
      animal studies and indicate that mechanisms of communication are likely to be
      multiple. There is need for the concepts generated in animal models to be
      translated to the human in the future.

PMID- 22404224
TI  - Protein kinase C betaII in diabetic complications: survey of structural,
      biological and computational studies.
AB  - INTRODUCTION: PKC-betaII is a conventional isoform of PKC. It is overexpressed in
      hyperglycemic conditions and is known to trigger various diabetic complications,
      mainly cardiovascular complications and to a certain extent nephropathy,
      neuropathy, retinopathy etc. Selective inhibition of this enzyme will be one of
      the favorable approaches to treat diabetes-mellitus-related complications. Due to
      high sequence similarities among PKC isoforms, selective inhibition of PKC-betaII
      is difficult and yet to be achieved successfully. AREAS COVERED: This review
      discusses the studies carried out in various aspects of PKC-betaII. The
      biological aspects, crystal structure data, structure-activity relationship study
      (SAR) and in silico studies related to PKC-betaII such as homology modeling,
      molecular docking, molecular dynamics, quantitative structure-activity
      relationship (QSAR) studies and pharmacophore modeling etc. are summarized.
      EXPERT OPINION: PKC-betaII is a potential target for treating diabetes-related
      complications. Selective inhibitors of this enzyme are under clinical trials but
      to date, success has not been achieved. Thus, extensive research is essential in
      this direction; the contribution of in silico tools in designing and optimizing
      selective inhibitors of PKC-betaII is valuable.

PMID- 22404223
TI  - Combining cognitive behavioral therapy and contingency management to enhance
      their effects in treating cannabis dependence: less can be more, more or less.
AB  - AIMS: To evaluate reciprocal enhancement (combining treatments to offset their
      relative weaknesses) as a strategy to improve cannabis treatment outcomes.
      Contingency management (CM) with reinforcement for homework completion and
      session attendance was used as a strategy to enhance cognitive-behavioral therapy
      (CBT) via greater exposure to skills training; CBT was used as a strategy to
      enhance durability of CM with rewards for abstinence. SETTING: Community-based
      out-patient treatment program in New Haven, Connecticut, USA. DESIGN: Twelve-week
      randomized clinical trial of four treatment conditions: CM for abstinence alone
      or combined with CBT, CBT alone or combined with CM with rewards for CBT session
      attendance and homework completion. PARTICIPANTS: A total of 127 treatment
      seeking young adults (84.3% male, 81.1% minority, 93.7% referred by criminal
      justice system, average age 25.7 years). MEASUREMENTS: Weekly urine specimens
      testing positive for cannabis, days of cannabis use via the time-line follow-back
      method. FINDINGS: Within treatment, reinforcing homework and attendance did not
      significantly improve CBT outcomes, and the addition of CBT worsened outcomes
      when added to CM for abstinence (75.5 versus 57.1% cannabis-free urine specimens,
      F = 2.25, P = 0.02). The CM for abstinence condition had the lowest percentage of
      cannabis-negative urine specimens and the highest mean number of consecutive
      cannabis-free urine specimens (3.3, F = 2.33, P = 0.02). Attrition was higher in
      the CBT alone condition, but random effect regression analyses indicated this
      condition was associated with the greatest rate of change overall. Cannabis use
      during the 1-year follow-up increased most rapidly for the two enhanced groups.
      CONCLUSIONS: Combining contingency management and cognitive-behavioural therapy
      does not appear to improve success rates of treatment for cannabis dependence in
      clients involved with the criminal justice system.

PMID- 22404225
TI  - Studies on the interactions between beta2 adrenergic receptor and Gs protein by
      molecular dynamics simulations.
AB  - The beta2 adrenergic receptor (beta2AR) plays a key role in the control of smooth
      muscle relaxation in airways, the therapy of asthma, and a series of other basic
      physiological functions. Recently, the crystal structure of the beta2AR-Gs
      protein complex was reported, which facilitates study of the activation mechanism
      of the beta2AR and G-protein-coupled receptors (GPCRs). In this work, we perform
      20 ns molecular dynamics (MD) simulations of the beta2AR-Gs protein complex with
      its agonist in an explicit lipid and water environment to investigate the
      activation mechanism of beta2AR. We find that during 20 ns MD simulation with a
      nanobody bound the interaction between the beta2AR and the Gs protein is stable
      and the whole system is equilibrated within 6 ns. However, without a nanobody
      stabilizing the complex, the agonist triggers conformational changes of beta2AR
      sequentially from the extracellular region to the intracellular region,
      especially the intracellular parts of TM3, TM5, TM6, and TM7, which directly
      interact with the Gs protein. Our results show that the beta2AR-Gs protein
      complex makes conformational changes in the following sequence: (1) an agonist
      bound part of beta2AR, (2) the intracellular region of beta2AR, and (3) the Gs
      protein.

PMID- 22404226
TI  - Effects of long-pulsed 1,064-nm neodymium-doped yttrium aluminum garnet laser on
      dermal collagen remodeling in hairless mice.
AB  - BACKGROUND: Nonablative lasers are used for dermal collagen remodeling. Although
      clinical improvements have been reported using various laser devices, the
      mechanism of dermal collagen remodeling remains unknown. OBJECTIVE: To
      investigate the effects of energy fluences of the long-pulsed neodymium-doped
      yttrium aluminum garnet (Nd:YAG) nonablative laser on dermal collagen remodeling
      and evaluate the dermal collagen remodeling mechanism. MATERIALS AND METHODS:
      Hairless mice were pretreated with ultraviolet B irradiation to produce photo
      damage. The laser treatment used a long-pulse 1,064-nm Nd:YAG laser at energy
      fluences of 20, 40, and 60 J/cm(2) . The amount of dermal collagen and
      expressions of transforming growth factor beta (TGF-beta), matrix
      metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1)
      of laser treated skin were compared with those of nontreated control skin.
      RESULTS: The long-pulse Nd:YAG laser treatment increased dermal collagen and
      significantly increased TGF-beta expression. The expression of MMP-1 decreased
      with low energy fluence. The expression of TIMP-1 was not significantly
      different. CONCLUSION: Long-pulsed 1,064-nm Nd:YAG laser increases the dermal
      collagen in association with the increased expression of TGF-beta.

PMID- 22404227
TI  - Crossing the fourth hurdle.
AB  - The fourth hurdle, the requirement that pharmaceutical manufacturers can
      demonstrate that their new products represent good value for money as well as
      being of good quality, effective and safe, is increasingly being required by
      healthcare systems. In crossing this 'fourth' hurdle, companies will usually need
      to demonstrate that their products are more effective than relevant comparators
      and that the increased cost is offset by the enhanced benefits. Decision makers,
      however, must draw their conclusions not only on the basis of the underpinning
      science but also on the social values of the people they serve.

PMID- 22404228
TI  - Stem cell-derived extracellular matrix enables survival and multilineage
      differentiation within superporous hydrogels.
AB  - Hydrophilic poly(ethylene glycol) diacrylate (PEGDA) hydrogel surfaces resist
      protein adsorption and are generally thought to be unsuitable for anchorage
      dependent cells to adhere. Intriguingly, our previous findings revealed that
      PEGDA superporous hydrogel scaffolds (SPHs) allow anchorage of bone marrow
      derived human mesenchymal stem cells (hMSCs) and support their long-term
      survival. Therefore, we hypothesized that the physicochemical characteristics of
      the scaffold impart properties that could foster cellular responses. We examined
      if hMSCs alter their microenvironment to allow cell attachment by synthesizing
      their own extracellular matrix (ECM) proteins. Immunofluorescence staining
      revealed extensive expression of collagen type I, collagen type IV, laminin, and
      fibronectin within hMSC-seeded SPHs by the end of the third week. Whether
      cultured in serum-free or serum-supplemented medium, hMSC ECM protein gene
      expression patterns exhibited no substantial changes. The presence of serum
      proteins is required for initial anchorage of hMSCs within the SPHs but not for
      the hMSC survival after 24 h. In contrast to 2D expansion on tissue culture
      plastic (TCP), hMSCs cultured within SPHs proliferate similarly in the presence
      or absence of serum. To test whether hMSCs retain their undifferentiated state
      within the SPHs, cell-seeded constructs were cultured for 3 weeks in stem cell
      maintenance medium and the expression of hMSC-specific cell surface markers were
      evaluated by flow cytometry. CD105, CD90, CD73, and CD44 were present to a
      similar extent in the SPH and in 2D monolayer culture. We further demonstrated
      multilineage potential of hMSCs grown in the PEGDA SPHs, whereby differentiation
      into osteoblasts, chondrocytes, and adipocytes could be induced. The present
      study demonstrates the potential of hMSCs to alter the "blank" PEGDA environment
      to a milieu conducive to cell growth and multilineage differentiation by
      secreting adhesive ECM proteins within the porous network of the SPH scaffolds.

PMID- 22404230
TI  - Electro-fenton and photoelectro-fenton degradation of sulfanilic acid using a
      boron-doped diamond anode and an air diffusion cathode.
AB  - The mineralization of sulfanilic acid has been studied by electro-Fenton (EF) and
      photoelectro-Fenton (PEF) reaction with UVA light using an undivided
      electrochemical cell with a boron-doped diamond (BDD) anode and an air diffusion
      cathode able to generate H(2)O(2). Organics were then oxidized by hydroxyl
      radicals formed at the anode surface from water oxidation and in the bulk from
      Fenton's reaction between generated H(2)O(2) and added Fe(2+). The UVA
      irradiation in PEF enhanced the production of hydroxyl radicals in the bulk,
      accelerating the removal of organics and photodecomposed intermediates like
      Fe(III)-carboxylate complexes. Partial decontamination of 1.39 mM sulfanilic acid
      solutions was achieved by EF until 100 mA cm(-2) at optimum conditions of 0.4 mM
      Fe(2+) and pH 3.0. The increase in current density and substrate content led to
      an almost total mineralization. In contrast, the PEF process was more powerful,
      yielding almost complete mineralization in less electrolysis time under
      comparable conditions. The kinetics for sulfanilic acid decay always followed a
      pseudo-first-order reaction. Hydroquinone and p-benzoquinone were detected as
      aromatic intermediates, whereas acetic, maleic, formic, oxalic, and oxamic acids
      were identified as generated carboxylic acids. NH(4)(+) ion was preferentially
      released in both treatments, along with NO(3)(-) ion in smaller proportion.

PMID- 22404231
TI  - Targeted binding of the M13 bacteriophage to thiamethoxam organic crystals.
AB  - Phage display screening with a combinatorial library was used to identify M13
      type bacteriophages that express peptides with selective binding to organic
      crystals of thiamethoxam. The six most strongly binding phages exhibit at least
      1000 times the binding affinity of wild-type M13 and express heptapeptide
      sequences that are rich in hydrophobic, hydrogen-bonding amino acids and proline.
      Among the peptide sequences identified, M13 displaying the pIII domain
      heptapeptide ASTLPKA exhibits the strongest binding to thiamethoxam in
      competitive binding assays. Electron and confocal microscopy confirm the specific
      binding affinity of ASTLPKA to thiamethoxam. Using atomic force microscope (AFM)
      probes functionalized with ASTLPKA expressing phage, we found that the average
      adhesion force between the bacteriophage and a thiamethoxam surface is 1.47 +/-
      0.80 nN whereas the adhesion force of wild-type M13KE phage is 0.18 +/- 0.07 nN.
      Such a strongly binding bacteriophage could be used to modify the surface
      chemistry of thiamethoxam crystals and other organic solids with a high degree of
      specificity.

PMID- 22404232
TI  - Characterization of lactic acid bacteria-based probiotics as potential heavy
      metal sorbents.
AB  - AIM: To isolate and characterize lactic acid bacteria (LAB) and determine whether
      they could potentially be used as heavy metal (cadmium and lead) absorbing
      probiotics. METHODS AND RESULTS: The study used 53 environmental (mud and sludge)
      samples to isolate cadmium- and lead-resistant LAB, by following spared plate
      technique. A total of 255 cadmium- and lead-resistant LAB were isolated from
      these samples. The survival of 26 of the LAB was found after passing through
      sequential probiotic characterizations. These 26 probiotic LAB exhibited
      remarkable variations in their metal-resistant and metal-removal abilities. Of
      26, seven (Cd54-2, Cd61-7, Cd69-12, Cd70-13, Pb82-8, Pb96-19 and Cd109-16) and
      four (Pb71-1, Pb73-2, Pb85-9 and Pb96-19) strains displayed relatively elevated
      cadmium- and lead-removal efficiencies from water, respectively, compare with
      that of the remaining strains. Strains Cd70-13 and Pb71-1 showed the highest
      cadmium (25%) and lead (59%) removal capacity from MRS (De Man, Rogosa and
      Sharpe) culture medium, respectively, amongst the selected strains and showed a
      good adhesive ability on fish mucus. A phylogenetic analysis of their 16S rDNA
      sequences revealed that the strains Cd70-13 and Pb71-1 belong to Lactobacillus
      reuteri. CONCLUSION: Excellent probiotic, metal sorption and adhesive
      characteristics of newly identified Lact. reuteri strains Cd70-13 and Pb71-1 were
      isolated, which indicated their high potential abilities to survive in the
      intestinal milieu and to uptake the tested metals from the environment.
      SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this is the first study
      that has aimed to isolate, characterize and identify metal-resistant LAB strains
      that have potential to be a probiotic candidate for food and in vivo challenge
      studies in the intestinal milieu of fish for the uptake and control of heavy
      metal bioaccumulation.

PMID- 22404234
TI  - Variant Carvajal syndrome with additional dental anomalies.
AB  - BACKGROUND: This paper aims to review the case of a girl who presented with a
      number of dental anomalies, in addition to unusual skin, nail and hair
      conditions. Tragically an undiagnosed cardiomyopathy caused unexpected sudden
      death. The case is discussed with reference to a number of dermatological and
      oral conditions which were considered as possible diagnoses. CASE REPORT: AW had
      been under long term dental care for prepubertal periodontitis, premature root
      resorption of primary teeth, soft tissue and dental anomalies, and angular
      cheilitis. Separately she had also been seen by several dermatologists with
      respect to palmar plantar keratosis, striae keratoderma, wiry hair and abnormal
      finger nails. Tragically the patient suffered a sudden unexpected death and the
      subsequent post mortem identified an undiagnosed dilated cardiomyopathy.
      CONCLUSION: The most likely diagnosis is that this case is a variant of Carvajal
      Syndrome with additional dental anomalies. To date we have been unable to
      identify mutations in the desoplakin gene. We aim to emphasise the importance of
      recognising these dental and dermatological signs when they present together as a
      potential risk factor for cardiac abnormalities.

PMID- 22404233
TI  - A decision analysis of long-term lithium treatment and the risk of renal failure.
AB  - OBJECTIVE: To establish whether lithium or anticonvulsant should be used for
      maintenance treatment for bipolar affective disorder (BPAD) if the risks of
      suicide and relapse were traded off against the risk of end-stage renal disease
      (ESRD). METHOD: Decision analysis based on a systematic literature review with
      two main decisions: (1) use of lithium or at treatment initiation and (2) the
      potential discontinuation of lithium in patients with chronic kidney disease
      (CKD) after 20 years of lithium treatment. The final endpoint was 30 years of
      treatment with five outcomes to consider: death from suicide, alive with stable
      or unstable BPAD, alive with or without ESRD. RESULTS: At the start of treatment,
      the model identified lithium as the treatment of choice. The risks of developing
      CKD or ESRD were not relevant at the starting point. Twenty years into treatment,
      lithium still remained treatment of choice. If CKD had occurred at this point,
      stopping lithium would only be an option if the likelihood of progression to ESRD
      exceeded 41.3% or if anticonvulsants always outperformed lithium regarding
      relapse prevention. CONCLUSION: At the current state of knowledge, lithium
      initiation and continuation even in the presence of long-term adverse renal
      effects should be recommended in most cases.

PMID- 22404235
TI  - Shining light on skin pigmentation: the darker and the brighter side of effects
      of UV radiation.
AB  - The term barrier function as applied to human skin often connotes the physical
      properties of this organ that provides protection from its surrounding
      environment. This term does not generally include skin pigmentation. However,
      skin pigmentation, which is the result of melanin produced in melanocytes
      residing in the basal layer of the skin and exported to the keratinocytes in the
      upper layers, serves equally important protective function. Indeed, changes in
      skin pigmentation are often the most readily recognized indicators of exposure of
      skin to damaging agents, especially to natural and artificial radiation in the
      environment. Several recent studies have shed new light on (1) the mechanisms
      involved in selective effects of subcomponents of UV radiation on human skin
      pigmentation and (2) the interactive influences between keratinocytes and
      melanocytes, acting as "epidermal melanin unit," that manifest as changes in skin
      pigmentation in response to exposure to various forms of radiation. This article
      provides a concise review of our current understanding of the effects of the
      nonionizing solar radiation, at cellular and molecular levels, on human skin
      pigmentation.

PMID- 22404236
TI  - Association between vitamin C deficiency and dialysis modalities.
AB  - AIM:   We designed a cross-sectional study to investigate plasma vitamin C level
      in patients who underwent maintenance haemodialysis (MHD) and continuous
      ambulatory peritoneal dialysis (CAPD) to explore whether there is a difference in
      vitamin C deficiency between MHD patients and CAPD patients. METHODS:   This
      investigation included 382 dialysis patients without vitamin C supplement before
      the study. Demographic characteristics, laboratory tests, ascorbic acid and total
      plasma vitamin C level were measured. A linear regression model was built to
      explore the association between vitamin C deficiency and dialysis modalities
      after adjusting for age, dialysis vintage, gender, Charlson index, modality of
      dialysis and hsCRP. RESULTS:   The range of plasma vitamin C level was from 0.48
      ug/mL to 31.16 ug/mL. 35.9% (n = 137) patients had severe vitamin C deficiency
      (<2 ug/mL). Plasma vitamin C level was inversely associated with age and dialysis
      vintage. After age and dialysis vintage were adjusted, vitamin C deficiency was
      associated with MHD. R square for model fitting was relatively low, which implied
      that there were other vitamin C influencing factors not included in the model.
      CONCLUSIONS:   Vitamin C deficiency is common in dialysis patients, especially in
      patients treated with MHD.

PMID- 22404237
TI  - Reliability of a set of protractors for direct anatomical measurements around the
      glenoid and humeral head rims.
AB  - Functional biomechanics studies of the glenohumeral (GH) soft tissues require an
      understanding of their sites of bony attachment. Anatomical positions of GH
      capsular structures have often been quantified relative to the rims of the
      glenoid and humeral head (HH). The aim of this study was twofold: (1) to quantify
      the reliability of a set of protractors that directly fit on to the glenoid and
      HH rims and (2) to use this to determine direct angular position referencing of
      landmarks and soft tissue attachment points. Three assessors independently used
      the protractors to assess nine prescribed landmarks on 30 dry bone specimens (15
      glenoids and 15 HHs) recording the angular positions of the structures relative
      to the glenoid and HH. The collected data showed high levels of validity as
      indicated by the protractor's intra- and inter-assessor reliabilities: 98.2 and
      98.7% for the glenoid component, and 96.2 and 96.5% for the humeral component,
      respectively. The device could be useful in anatomical studies, description of
      defects and pathologies on glenohumeral articulation, and planning of scapular
      reconstructive surgery.

PMID- 22404238
TI  - Simple maxillary reconstruction following total maxillectomy using artificial
      bone wrapped with vascularized tissue: five key points to ensure success.
AB  - CONCLUSION: Our new method for hard tissue maxillary reconstructions using
      artificial bone implants provides stable results during long-term follow-up.
      OBJECTIVE: To date, vascularized bone/cartilage grafting has been the most
      popular method for hard tissue reconstruction after total maxillectomy; however,
      such three-dimensional reconstruction requires complex and lengthy invasive
      surgery. We have developed a simple maxillary reconstruction procedure using
      artificial bone. METHODS: This study included six patients who had undergone hard
      tissue reconstructions using artificial bone (Ceratite(TM)) implants after total
      maxillectomies between October 2002 and October 2010. We considered the following
      five key points to ensure success: (1) the procedure was conducted in two stages
      without communicating with the nasal cavity and sinuses; (2) when constructing
      the artificial bone, the curvature was reduced; (3) the space for the implant was
      kept to a minimum; (4) the artificial bone implant was closely and accurately
      fixed to the stump of the zygomatic arch; and (5) the artificial bone implant was
      wrapped with a vascularized tissue flap. RESULTS: The follow-up period ranged
      from 12 to 94 months. The postoperative zygomatic contour was maintained
      satisfactorily in all patients with no signs of late complications.

PMID- 22404239
TI  - Monitoring the risk of birth defects associated with atazanavir exposure in
      pregnancy.

PMID- 22404240
TI  - A role for neuropeptide Y in the gender-specific gastrointestinal, corticosterone
      and feeding responses to stress.
AB  - BACKGROUND AND PURPOSE: Exposure to an acute stress inhibits gastric emptying and
      stimulates colonic transit via central neuropeptide Y (NPY) pathways; however,
      peripheral involvement is uncertain. The anxiogenic phenotype of NPY(-/-) mice is
      gender-dependent, raising the possibility that stress-induced gastrointestinal
      (GI) responses are female-dominant through NPY. The aim of this study was to
      determine GI transit rates, corticosterone levels and food intake after acute
      restraint (AR) or novel environment (NE) stress in male and female NPY(-/-) and
      WT mice. EXPERIMENTAL APPROACH: Upper gastrointestinal transit (UGIT)
      (established 30 min after oral gavage) and corticosterone levels were determined
      under basal or restrained conditions (30 min) and after treatment i.p. with Y(1)
      antagonist BIBO3304 or Y(2) antagonist BIIE0246. Faecal pellet output (FPO) was
      established after AR and treatment i.p. with NPY in the NE, as were colonic bead
      expulsion rates. KEY RESULTS: UGIT and FPO were similar in unrestrained male and
      female mice. NPY(-/-) females displayed significantly slower UGIT than NPY(-/-)
      males after AR, but both genders displayed significantly higher FPO and reduced
      food intake relative to WT counterparts. Peripheral NPY treatment increased bead
      expulsion time in WT mice. AR male NPY(-/-) mice had higher levels of
      corticosterone than male WT mice; whilst in AR WT mice, after peripheral Y(1) and
      Y(2) receptor antagonism in males, and Y(2) antagonism in females, corticosterone
      was significantly elevated. CONCLUSIONS AND IMPLICATIONS: NPY possesses a role in
      the gender-dependent susceptibility to stress-induced GI responses. Furthermore,
      NPY inhibits GI motility through Y(2) receptors and corticosterone release via
      peripheral Y(1) and Y(2) receptors.

PMID- 22404242
TI  - Predicting developmental outcomes in very preterm infants: validity of a neonatal
      neurobehavioral assessment.
AB  - AIM: This study explored inter-rater reliability, discriminative, construct and
      predictive validity of the Neurobehavioral Assessment of the Preterm Infant
      (NAPI) in a gestational-age-based cohort. METHODS: The NAPI was conducted at 35
      weeks post-menstrual age for 170 infants born <32 weeks. Cognitive and motor
      development was assessed at 2 years using the Mental Development Index (MDI) and
      Psychomotor Development Index (PDI) of Bayley Scales of Infant Development-II for
      159 infants. RESULTS: Only NAPI motor and irritability scores were significantly
      different between very (29-3 w) and extremely preterm (<28 w) infants. Results
      regarding construct validity were variable: there were weak correlations between
      NAPI motor scores and gestational age (r = -0.23; p = 0.003), days in NICU (r = 
      0.24; p = 0.001); NAPI alertness scores and days in NICU (r = -0.16; p = 0.037);
      and NAPI irritability scores and gestational age (r = 0.21; p = 0.006). There
      were no significant associations with other markers of adverse outcome. Only NAPI
      irritability scores were correlated with MDI scores (r = -0.16; p = 0.040) but
      accounted for little additional variance after adjustment for neonatal factors
      (DeltaR(2) = 0.035; p = 0.012). CONCLUSION: We found little evidence of the
      utility of the NAPI as a measure of short-term neurobehavioural function or for
      predicting neurodevelopmental outcomes in very preterm infants. It may have
      greater predictive power when used serially to detect delayed neurobehavioural
      maturation.

PMID- 22404241
TI  - Local infiltration analgesia with levobupivacaine compared with intrathecal
      morphine in total hip arthroplasty patients.
AB  - BACKGROUND: Recently, local infiltration analgesia (LIA) has been promoted for
      pain control after total hip arthroplasty (THA). We hypothesized that LIA would
      offer equal analgesic efficacy but less adverse effects, e.g., nausea and
      vomiting, when compared with an established regimen [intrathecal morphine (it-M)]
      after THA. METHODS: This randomized controlled trial comprised 60 patients
      undergoing THA under spinal anaesthesia. For LIA, the surgeon administered
      levobupivacaine, ketorolac and epinephrine at the surgical site intraoperatively.
      LIA patients received a LIA top-up through a wound catheter on the morning of the
      1st post-operative day (POD). In group it-M, 0.1 mg morphine was given together
      with the spinal anaesthetic. Study parameters included pain scores, vital
      parameters and side effects, e.g., post-operative nausea and vomiting (PONV).
      Besides, levobupivacaine plasma concentrations were determined in 10 LIA
      patients. RESULTS: The median (25th/75th percentiles) rescue oxycodone demand
      differed significantly with LIA 15 (10/25) mg vs. 8.5 (1.5/15) mg with it-M (P <
      0.006) during the day of surgery, but not anymore on 1st or 2nd POD. The LIA top
      up had no effect. However, both analgesic regimens resulted in comparable pain
      scores and patient satisfaction. PONV incidence and medication did not vary
      significantly. LIA offered certain advantages regarding early post-operative
      mobilization. Maximum levobupivacaine plasma concentrations (229-580 ng/ml)
      remained under the toxic level. CONCLUSIONS: While LIA might enable earlier
      mobilization after THA, it was not associated with less nausea as compared with
      it-M. Less rescue oxycodone was given early after it-M, but urinary retention was
      more common in that group.

PMID- 22404243
TI  - Perceptual shifts of priority: a qualitative study bringing emotional
      intelligence to the foreground for nurses in talk-based therapy roles.
AB  - This paper presents the findings of a qualitative study conceptually framed by
      social constructionism that explored the experiences of mental health nurses
      engaging in talk-based therapy roles. Constructions from the participants'
      narratives are shown to have a powerful resonance with the construct of emotional
      intelligence, a resonance also echoed from the literature, and policies from the
      UK identified within the paper. Forwarded is that rather than prioritizing the
      development of technical approaches of specific therapies, nurses should equally
      be prepared for talk-based therapy roles through developing their emotionally
      intelligence capabilities.

PMID- 22404244
TI  - Associations between self-reported illness and non-drinking in young adults.
AB  - AIMS: This study investigated associations between self-reported illness, social
      factors and health behaviours and non-drinking among young people aged 18-34
      years. DESIGN: Logistic regression analysis of cross-sectional national survey
      data, collected from the Health Survey for England 2006 and 2008. Data were
      collected through face-to-face interviews and are self-reported. PARTICIPANTS AND
      SETTINGS: A total of 2826 male and 3618 females aged 18-34 years drawn from a
      nationally representative multi-stage stratified probability sampling design
      across England. MEASUREMENTS: Non-drinkers were based on those who reported 'no'
      to drinking alcohol currently. Exposure measures included self-reports of having
      a limiting long-standing illness, long-standing illness or self-reported poor
      health. We adjusted for ethnicity, income, education, general physical activity
      and other factors. FINDINGS: Having a limiting long-standing illness during early
      adulthood increased the odds of being a non-drinker 1.74 times for men (P < 0.01)
      and 1.45 times for women (P < 0.01). In both men and women belonging to the
      lowest income quintile or having no qualifications was associated with increased
      odds of being a non-drinker (P < 0.001), indicating that the social gradient in
      non-drinking begins at an early age. Men and women aged 18-34 years with the
      lowest activity levels were also more likely to be non-drinkers (P < 0.01).
      CONCLUSION: Young adults who have a limiting long-standing illness are more
      likely not to drink alcohol even after adjusting for a range of social and
      demographic measures. Studies on the putative health benefits of moderate alcohol
      consumption later in life need to take account of early life history.

PMID- 22404245
TI  - Multimodality imaging of aortic dimensions: comparison of transthoracic
      echocardiography with multidetector row computed tomography.
AB  - BACKGROUND: With recent advances in multimodality cardiac imaging, a number of
      methods exist for the noninvasive assessment of aortic disease. Although
      multidetector row computed tomography (MDCT) remains the gold standard for aortic
      measurements, there are a number of limitations including radiation and contrast
      induced nephropathy. Transthoracic echocardiography (TTE) is an alternative to
      MDCT for providing accurate anatomic assessment of aortic root and ascending
      aorta dimensions. OBJECTIVES AND METHODS: To determine the accuracy of two
      dimensional (2D) TTE for determining aortic measurements in comparison to MDCT, a
      retrospective study of individuals with varying aortic root and ascending aorta
      dimensions was performed. RESULTS: There were 116 patients (77 males, mean age 49
      +/- 12 years) in total. The maximum aortic diameters by 2D TTE were 26.1 +/- 4.3
      mm (annulus), 32.4 +/- 5.6 mm (sinuses), 30.1 +/- 5.9 mm (sinotubular [ST]
      junction), and 33.4 +/- 7.3 mm (ascending aorta). The maximum aortic diameters by
      MDCT were 30.1 +/- 4.1 mm (annulus), 35.8 +/- 5.8 mm (sinuses), 33.2 +/- 5.9 mm
      (ST junction), and 37.4 +/- 7.6 mm (ascending aorta). There was good to excellent
      correlation between 2D TTE and MDCT at all four levels of the aorta (annulus: r =
      0.84; sinuses: r = 0.93; ST junction: r = 0.93; ascending aorta: r = 0.88). There
      was a consistent underestimation of aortic measurements obtained by 2D TTE when
      compared to MDCT. CONCLUSION: 2DTTE is a feasible, accurate, and reproducible
      method for the noninvasive assessment of thoracic aortic diameters as compared to
      MDCT.

PMID- 22404247
TI  - Panobinostat  for the treatment of multiple myeloma.
AB  - INTRODUCTION: Multiple myeloma (MM) is a B-cell malignancy characterized by
      proliferation of monoclonal plasma cells in the bone marrow. Although new
      therapeutic options have been introduced and response rates have improved in
      recent years, MM still remains incurable and new treatment options are urgently
      needed. The histone deacetylase inhibitors (HDACi) are a new class of anticancer
      agents in early clinical development in many malignancies including MM. HDACi
      target the enzyme histone deacetylase (HDAC) involved in the deacetylation of
      histone and non-histone cellular proteins that play important roles in epigenetic
      regulation of gene expression inducing death, apoptosis and cell cycle arrest in
      cancer cells. Panobinostat (LBH589) is a highly potent HDACi with demonstrated
      antitumor activities at low nanomolar concentration in several preclinical
      studies and its clinical efficacy is currently under investigation in several
      clinical trials. AREA COVERED: In this review the authors discuss the role of
      HDACs in the regulation of gene expression and the biological mechanisms
      mediating the anticancer effects of HDACi with particular focus on the recent
      development of panobinostat as anti-MM agent in preclinical and clinical studies.
      EXPERT OPINION: As a 'multi-target' drug, panobinostat appears attractive as
      potential anti-MM therapeutic for its ability to modulate a variety of biological
      pathways essential in MM biology. This 'multi-target' property of panobinostat
      may also be one its major shortcomings, and a better understanding of its
      mechanisms of action and targets will permit to identify the best combination
      therapies that will ultimately overcome and improve outcomes in MM patients.

PMID- 22404249
TI  - Atomdroid: a computational chemistry tool for mobile platforms.
AB  - We present the implementation of a new molecular mechanics program designed for
      use in mobile platforms, the first specifically built for these devices. The
      software is designed to run on Android operating systems and is compatible with
      several modern tablet-PCs and smartphones available in the market. It includes
      molecular viewer/builder capabilities with integrated routines for geometry
      optimizations and Monte Carlo simulations. These functionalities allow it to work
      as a stand-alone tool. We discuss some particular development aspects, as well as
      the overall feasibility of using computational chemistry software packages in
      mobile platforms. Benchmark calculations show that through efficient
      implementation techniques even hand-held devices can be used to simulate midsized
      systems using force fields.

PMID- 22404248
TI  - Evaluation of cytotoxic T-cell activation, chemokine receptors, and adhesion
      molecules in blood and serum in patients with oral lichen planus.
AB  - BACKGROUND: Our purpose is to study cytotoxic T-cell activation (through
      evaluation of CD8+CD40+ and CD8+CD154+ cells), chemokine receptors (through
      evaluation of CD8+CD184+ and CD8+CD195+ cells), and adhesion molecules (through
      evaluation of CD8+CD152+ cells) which play a part in cell activation in blood and
      serum samples of patients with OLP and then to compare them with healthy
      controls. METHODS: Thirty patients with OLP, and 30 matched healthy controls
      participated. The mean ages of OLP patients and controls were 51,10 +/- 12,25 and
      48,09 +/- 11,92, respectively. Percentage of apoptotic cells, granzyme-B+, CD8+,
      CD8+CD40+, CD8+CD152+ (CTLA-4), CD8+CD154+(CD40L), CD8+CD184+(CXCR-4) and
      CD8+CD195+(CCR-5) were detected by immunophenotyping on flow cytometry. Apoptosis
      measurements were accomplished with Annexin V/Propidium Iodide kit. RESULTS: A
      higher percentage of CD8+CD154+ and granzyme-B+ and a lower percentage of CD8+,
      CD8+CD184+ and apoptotic cells were found in OLP patients than in controls. No
      statistical differences were observed in the percentages of the other markers
      between groups. CONCLUSIONS: It is observed that because of increase in granzyme
      B+ and CD154 which is the activation marker, CD8+ cells present efforts to
      sustain their activity even though decrease in their cell number. Lower levels of
      CD8+CD184+ cells in OLP than control is evaluated as a factor that makes OLP to
      be localised in our study. In addition, our findings lead us to think that there
      may be some changes in apoptosis pathways of the cells. But this needs to be
      clarified by further studies exploring the mechanisms of the apoptosis in OLP
      patients.

PMID- 22404250
TI  - Sclerotherapy of telangiectasias: a painless two-step technique.
AB  - BACKGROUND: Sclerotherapy of telangiectasias and reticular leg veins can be
      unpleasant and painful for some patients. OBJECTIVE: To determine pain level with
      two different sclerotherapy techniques in a prospective randomized trial.
      METHODS: Patients with symmetrical telangiectasias and reticular veins on both
      legs (C(1A) or (S)E(P)A(S)P(N1) were randomized to the standard (successive
      injections of chromated glycerin mixed with one-third lidocaine-epinephrine 1%)
      or two-step technique (first treating only reticular veins with a single
      injection at the base of each cluster of telangiectasias and then successively
      injecting all remaining telangiectasias a few minutes later. Pain was assessed
      using a 100-point visual analogue scale (0 = no pain, 100 = maximum pain).
      RESULTS: Data from 53 consecutive patients could be evaluated. The two-step
      technique was significantly less painful (28.2) than the standard technique
      (40.6, p < .001). CONCLUSION: The two-step technique with chromated glycerin
      mixed with one-third lidocaine-epinephrine 1% significantly reduces sclerotherapy
      pain. This may be a useful technique for patients who are particularly sensitive
      or afraid of sclerotherapy.

PMID- 22404251
TI  - Tuning of collagen triple-helix stability in recombinant telechelic polymers.
AB  - The melting properties of various triblock copolymers with random coil middle
      blocks (100-800 amino acids) and triple helix-forming (Pro-Gly-Pro)(n) end blocks
      (n = 6-16) were compared. These gelatin-like molecules were produced as secreted
      proteins by recombinant yeast. The investigated series shows that the melting
      temperature (T(m)) can be genetically engineered to specific values within a very
      wide range by varying the length of the end block. Elongation of the end blocks
      also increased the stability of the helices under mechanical stress. The length
      dependent melting free energy and T(m) of the (Pro-Gly-Pro)(n) helix appear to be
      comparable for these telechelic polymers and for free (Pro-Gly-Pro)(n) peptides.
      Accordingly, the T(m) of the polymers appeared to be tunable independently of the
      nature of the investigated non-cross-linking middle blocks. The flexibility of
      design and the amounts in which these nonanimal biopolymers can be produced (g/L
      range) create many possibilities for eventual medical application.

PMID- 22404252
TI  - Targeting airway remodelling in asthma: the how, what and where?

PMID- 22404253
TI  - Influence of rubber dam on objective and subjective parameters of stress during
      dental treatment of children and adolescents - a randomized controlled clinical
      pilot study.
AB  - BACKGROUND: Rubber dam is recommended for isolating the working field during
      adhesive dentistry procedures; however, dentists often omit rubber dam,
      particularly in paediatric dentistry, supposing that it would stress the patient.
      AIM: The aim of this study was to evaluate stress parameters during a
      standardized dental treatment procedure performed with or without rubber dam. The
      treatment time was measured as a secondary outcome variable. DESIGN: This study
      was designed as a randomized, controlled, clinical study with 72 patients (6-16
      years; mean age, 11.1). During standardized fissure sealing procedures, objective
      parameters of stress (e.g., skin resistance, breath rate) were recorded. The
      operator's stress level was measured by pulse rate. Subjective pain (patients)
      and stress perception (operator) were evaluated by an interview. RESULTS: The
      breath rate was significantly (P<0.05) lower and the skin resistance level was
      significantly higher during treatment with rubber dam compared to the control
      group. Subjective pain perception was significantly lower for the test group. The
      treatment time needed for the fissure sealing procedure was 12.4% less in the
      test group. CONCLUSION: Isolation with rubber dam caused less stress in children
      and adolescents compared to relative isolation with cotton rolls if applied by an
      experienced dentist.

PMID- 22404254
TI  - Acetylcholinesterase responsive polymeric supra-amphiphiles for controlled self
      assembly and disassembly.
AB  - We have fabricated enzyme responsive polymeric supra-amphiphiles by mixing a
      block copolymer of poly(ethylene glycol)-block-poly(acrylic acid) with
      myristoylcholine chloride in water. The polymeric supra-amphiphiles self-assemble
      into spherical aggregates with sizes varying from about 40 to 150 nm. Moreover,
      the spherical aggregates can be disassembled triggered by acetylcholinesterase,
      an enzyme which can cut off the ester linkage of myristoylcholine chloride. Nile
      red can be loaded into the spherical aggregates and released in several hours
      upon the treatment of acetylcholinesterase. The releasing rate is rather fast
      considering that it takes more than 150 h for Nile red to diffuse out of the
      spherical aggregates without addition of acetylcholinesterase. It is anticipated
      that the new enzyme responsive polymeric supra-amphiphile may be explored as a
      carrier for drug delivery.

PMID- 22404255
TI  - The mammalian bony labyrinth reconsidered, introducing a comprehensive geometric
      morphometric approach.
AB  - The bony labyrinth in the temporal bone houses the sensory systems of balance and
      hearing. While the overall structure of the semicircular canals and cochlea is
      similar across therian mammals, their detailed morphology varies even among
      closely related groups. As such, the shape of the labyrinth carries valuable
      functional and phylogenetic information. Here we introduce a new, semilandmark
      based three-dimensional geometric morphometric approach to shape analysis of the
      labyrinth, as a major improvement upon previous metric studies based on linear
      measurements and angles. We first provide a detailed, step-by-step description of
      the measurement protocol. Subsequently, we test our approach using a
      geographically diverse sample of 50 recent modern humans and 30 chimpanzee
      specimens belonging to Pan troglodytes troglodytes and P. t. verus. Our
      measurement protocol can be applied to CT scans of different spatial resolutions
      because it primarily quantifies the midline skeleton of the bony labyrinth.
      Accurately locating the lumen centre of the semicircular canals and the cochlea
      is not affected by the partial volume and thresholding effects that can make the
      comparison of the outer border problematic. After virtually extracting the bony
      labyrinth from CT scans of the temporal bone, we computed its midline skeleton by
      thinning the encased volume. On the resulting medial axes of the semicircular
      canals and cochlea we placed a sequence of semilandmarks. After Procrustes
      superimposition, the shape coordinates were analysed using multivariate
      statistics. We found statistically significant shape differences between humans
      and chimpanzees which corroborate previous analyses of the labyrinth based on
      traditional measurements. As the geometric relationship among the semilandmark
      coordinates was preserved throughout the analysis, we were able to quantify and
      visualize even small-scale shape differences. Notably, our approach made it
      possible to detect and visualize subtle, yet statistically significant (P =
      0.009), differences between two chimpanzee subspecies in the shape of their
      semicircular canals. The ability to discriminate labyrinth shape at the
      subspecies level demonstrates that the approach presented here has great
      potential in future taxonomic studies of fossil specimens.

PMID- 22404256
TI  - Traumatic events and suicidal behaviour in the Nigerian Survey of Mental Health
      and Well-Being.
AB  - OBJECTIVE: Not much is known about the role of different traumatic events in
      predicting suicidal outcomes. We investigated the association of specific
      traumatic events with different suicidal outcomes. METHOD: Data are from the
      Nigerian Survey of Mental Health and Well-Being, a multistage probability
      household survey of persons aged 18 years and over. Information on traumatic
      events and suicidal behaviours (ideation, plan and attempts) was collected in
      face-to-face interviews using the Composite International Diagnostic Interview
      (CIDI.3) from a subsample of the respondents (N = 2143). RESULTS: At least one
      traumatic event was reported by 63% of the sample. Traumatic events were more
      likely to have been experienced by individuals with different suicidal outcomes,
      with a dose-response relationship between the number of traumatic events and
      suicide ideation. The risks of suicidal ideation were elevated among persons with
      a history of combat experience (OR 6.3 95% CI 1.8-21.8) and those with exposure
      to war (OR 4.2; 95% CI 1.6-10.6), while that of suicidal attempt was increased
      among persons with experience of interpersonal violence (OR 4.3; 95% CI 1.4
      13.0). CONCLUSION: Traumatic events are common in the general population. This
      report highlights the role of traumatic events (especially those related to
      violence) in predicting suicidal behaviour.

PMID- 22404257
TI  - Early breast development in girls after prenatal exposure to non-persistent
      pesticides.
AB  - Contemporary American and European girls experience breast development at earlier
      ages compared with 15-20 years ago. Alterations in BMI alone cannot account for
      these changes. Several currently used pesticides possess endocrine disrupting
      properties and may interfere with reproductive development, but human data are
      sparse. We examined girls whose mothers worked in greenhouses in the first
      trimester of pregnancy to assess the long-term effects of prenatal pesticide
      exposure on puberty. Mothers were prenatally categorized as exposed or unexposed
      to pesticides. We studied the offspring of these greenhouse workers, and
      evaluated the anthropometry, pubertal staging in the girls, and blood samples
      were drawn at 3 months of age (n = 90) and again once at school age (6-11 years,
      n = 83). No clinical and biochemical differences were found between the exposed
      and unexposed girls at 3 months of age. Mean onset of B2+ was 8.9 years (95% CI:
      8.2; 9.7) in prenatally exposed girls, compared with 10.4 years (9.2; 17.6) in
      the unexposed (p = 0.05), and 10.0 (9.7-10.3) years in a Danish reference
      population (p = 0.001). Exposed girls had higher serum androstenedione levels
      (geometric means: 0.58 vs. 0.79 nmol/L, p = 0.046) and lower Anti-Mullerian
      Hormone (AMH) compared with the unexposed (geometric means: 16.4 vs. 21.3 pmol/L,
      p > 0.05) and the reference group (20.2 pmol/L, p = 0.012). Levels of
      testosterone, estradiol, prolactin, FSH, LH, SHBG, DHEAS, DHT, Inhibin A and
      Inhibin B did not differ between the groups. In conclusion, our findings suggest
      that prenatal exposure to currently approved pesticides may cause earlier breast
      development in girls. This association appeared not to be because of changes in
      gonadotropins, but rather to higher androgen levels, which indirectly may
      increase oestrogens through aromatization. In addition, lower serum AMH levels
      indicated a reduced pool of antral ovarian follicles. The long-term consequences
      of our findings with regard to establishment of future reproductive function
      still remain unknown.

PMID- 22404258
TI  - Vestibular evoked myogenic potential in unilateral vestibular hypofunction.
AB  - CONCLUSION: The patients with unilateral chronic vestibular hypofunction detected
      by caloric test demonstrated at least some sort of altered vestibular evoked
      myogenic potential (VEMP) in 63.63% of the cases. The VEMP altered side was the
      same as the unilateral vestibular hypofunction side in 54.54% of the cases and
      was the opposite side in 24.24%. The VEMP test improved functional vestibular
      assessment in patients with unilateral caloric hypofunction. OBJECTIVES: To
      analyze VEMP in patients with chronic dizziness and unilateral vestibular
      hypofunction and verify findings according to the side and structures involved.
      METHODS: This was an observational study. In all, 66 subjects were evaluated by
      VEMP (tone bursts/1000 Hz/100 dBnHL/bandpass filtered 10-1500 Hz/4.3 Hz rate), 33
      with unilateral vestibular hypofunction, detected by caloric test and clinical
      data, and 33 control subjects, matched by gender and age. Amplitude of the p13
      n23, asymmetry index of the amplitude, p13 and n23 latencies, p13 and n23
      interaural difference and threshold were analyzed. Simple descriptive analysis
      was carried out using the t test, Shapiro-Wilks test, and Mann-Whitney test, p <
      0.05. RESULTS: VEMP was altered in patients with unilateral vestibular
      hypofunction in 63.63% of cases. Thirteen of them were ipsilateral to the
      vestibular hypofunction and three were contralateral to the vestibular
      hypofunction. In five cases, VEMP were bilaterally altered.

PMID- 22404259
TI  - Effect of biliary drainage on chemotherapy in patients with biliary tract cancer:
      an exploratory analysis of the BT22 study.
AB  - BACKGROUND/PURPOSE: Complications from biliary drainage in biliary tract cancer
      (BTC) may influence the relative dose intensity of chemotherapy or increase
      adverse events during chemotherapy. BT22 was a randomized phase II trial, the
      results of which were consistent with those of a phase III trial in non-Japanese
      that demonstrated the effectiveness of gemcitabine plus cisplatin combination
      therapy (GC) in BTC. The purpose of this exploratory analysis of the BT22 study
      was to identify the possible effects of biliary drainage on the efficacy and
      safety of GC or gemcitabine monotherapy (G). PATIENTS AND METHODS: The 83 BTC
      patients who received GC or G in BT22 were retrospectively analysed in two
      subgroups dependent upon whether biliary drainage was performed before study
      entry. Efficacy and safety of treatment (GC vs. G) were compared in these two
      groups. RESULTS: The GC arm had a higher 1-year survival rate and longer median
      survival time (MST) than the G arm independent of prior biliary drainage.
      Patients in the drainage subgroup developed cholangitis more frequently, however,
      the frequency of grade 3/4 adverse events did not differ between the treatment
      regimens with/without drainage. CONCLUSIONS: Biliary drainage before chemotherapy
      did not affect the therapeutic efficacy or tolerability of chemotherapy using G
      or GC.

PMID- 22404261
TI  - Factors in perioperative care that determine blood loss in liver surgery.
AB  - OBJECTIVES: Excessive blood loss during liver surgery contributes to
      postoperative morbidity and mortality and the minimizing of blood loss improves
      outcomes. This study examines pre- and intraoperative factors contributing to
      blood loss and identifies areas for improvement. METHODS: All patients who
      underwent elective hepatic resection between June 2007 and June 2009 were
      identified. Detailed information on the pre- and perioperative clinical course
      was analysed. Univariate and multivariate analyses were used to identify factors
      associated with intraoperative blood loss. RESULTS: A total of 175 patients were
      studied, of whom 95 (54%) underwent resection of three or more segments. Median
      blood loss was 782 ml. Greater blood loss occurred during major resections and
      prolonged surgery and was associated with an increase in postoperative
      complications (P= 0.026). Peak central venous pressure (CVP) of >10 cm H(2)O was
      associated with increased blood loss (P= 0.01). Although no differences in case
      mix were identified, blood loss varied significantly among anaesthetists, as did
      intraoperative volumes of i.v. fluids and transfusion practices. CONCLUSIONS:
      This study confirms a relationship between CVP and blood loss in hepatic
      resection. Intraoperative CVP values were higher than those described in other
      studies. There was variation in the intraoperative management of patients.
      Collaboration between surgical and anaesthesia teams is required to minimize
      blood loss and the standardization of intraoperative anaesthesia practice may
      improve outcomes following liver surgery.

PMID- 22404260
TI  - Multi-institutional analysis of pancreatic adenocarcinoma demonstrating the
      effect of diabetes status on survival after resection.
AB  - BACKGROUND: The effect of diabetes on survival after resection pancreatic ductal
      carcinoma (PDAC) is unclear. The present study was undertaken to determine
      whether pre-operative diabetes has any predictive value for survival. METHODS: A
      retrospective review from seven centres was performed. Metabolic factors, tumour
      characteristics and outcomes of patients undergoing resection for PDAC were
      collected. Univariate and multivariable analyses were performed to determine
      factors associated with disease-free (DFS) and overall survival (OS). RESULTS: Of
      the 509 patients in the present study, 31.2% had diabetes. Scoring systems were
      devised to predict OS and DFS based on a training set (n= 245) and were
      subsequently tested on an independent set (n= 264). Pre-operative diabetes (P <
      0.001), tumour size >2 cm (P= 0.001), metastatic nodal ratio >0.1 (P < 0.001) and
      R1 margin (P < 0.001) all correlated with DFS and OS on univariate analysis.
      Scoring systems were devised based on multivariable analysis of the above
      factors. Diabetes and the metastatic nodal ratio were the most important factors
      in each system, earning two points for OS and four points for DFS. These scoring
      systems significantly correlated with both DFS (P < 0.001) and OS (P < 0.001).
      CONCLUSION: Pre-operative diabetes status provides useful information that can
      help to stratify patients in terms of predicted post-operative OS and DFS.

PMID- 22404262
TI  - Patient views through the keyhole: new perspectives on single-incision vs.
      multiport laparoscopic cholecystectomy.
AB  - OBJECTIVES: Single-incision laparoscopic cholecystectomy (SILC) may be associated
      with less pain, shorter hospital stay and better cosmetic results than multiport
      laparoscopic cholecystectomy (MLC). Advocates suggest that patients prefer SILC,
      although research directly addressing the question of patient preferences is
      limited. This study aimed to assess patient preferences using currently available
      evidence. METHODS: Patients awaiting elective cholecystectomy were shown a series
      of postoperative images taken after SILC or MLC and asked which procedure this
      led them to prefer. This was repeated after patients had completed a
      questionnaire constructed using published objective data comparing patient
      reported outcomes of SILC and MLC. RESULTS: The study was completed by 113
      consecutive patients. After their initial viewing of the images, 16% of subjects
      preferred MLC. Younger age, lower body mass index and female sex were associated
      with choosing SILC. After completing the questionnaire, 88% of patients preferred
      MLC (P < 0.001). Patients ranked the level of risk for complications and
      postoperative pain above cosmetic results in determining their choice of
      procedure. CONCLUSIONS: Patients' initial preference when presented with cosmetic
      appearance was for SILC. When contemporary outcome data were included, the
      majority chose MLC. This underlines the need to fully inform patients during the
      consent process and indicates that patient views of SILC may differ from the
      views of those introducing the technology.

PMID- 22404264
TI  - Meta-analysis of one- vs. two-stage laparoscopic/endoscopic management of common
      bile duct stones.
AB  - BACKGROUND: The present study is a meta-analysis of English articles comparing
      one-stage [laparoscopic common bile duct exploration or intra-operative
      endoscopic retrograde cholangiopancreatography (ERCP)] vs. two-stage
      (laparoscopic cholecystectomy preceded or followed by ERCP) management of common
      bile duct stones. METHODS: MEDLINE/PubMed and Science Citation Index databases
      (1990-2011) were searched for randomized, controlled trials that met the
      inclusion criteria for data extraction. Outcomes were calculated as odds ratios
      (ORs) with 95% confidence intervals (CIs) using RevMan 5.1. RESULTS: Nine trials
      with 933 patients were studied. No significant differences was observed between
      the two groups with regard to bile duct clearance (OR, 0.89; 95% CI, 0.65-1.21),
      mortality (OR, 1.2; 95% CI, 0.32-4.52), total morbidity (OR, 0.75; 95% CI, 0.53
      1.06), major morbidity (OR, 0.95; 95% CI, 0.60-1.52) and the need for additional
      procedures (OR, 1.58; 95% CI, 0.76-3.30). CONCLUSIONS: Outcomes after one-stage
      laparoscopic/endoscopic management of bile duct stones are no different to the
      outcomes after two-stage management.

PMID- 22404263
TI  - Factors linked to longterm survival of patients with hepatocellular carcinoma
      accompanied by tumour thrombus in the major portal vein after surgical resection.
AB  - OBJECTIVES: The prognosis in patients with hepatocellular carcinoma (HCC)
      accompanied by main portal vein tumour thrombus (MPVTT) is poor. The aim of this
      study was to clarify the factors linked to survival of >5 years after hepatectomy
      in HCC patients with MPVTT. METHODS: Twenty-nine HCC patients with MPVTT were
      divided into two groups comprising, respectively, patients who survived >5 years
      after hepatectomy (survivors, n= 5) and those who did not (non-survivors, n= 24).
      The two groups were compared. RESULTS: Overall survival rates at 1, 3 and 5 years
      were 62.1%, 24.1% and 17.2%, respectively. Four (80.0%) 5-year survivors had
      recurrences of HCC in which the number of recurrent nodules was under four. Three
      (21.4%) of the 14 non-survivors who underwent curative resection experienced
      recurrences of HCC and all of them demonstrated fewer than four recurrent nodules
      (P= 0.0114). Local therapy, such as radiofrequency ablation and resection of
      recurrence, had more often been used in survivors than in non-survivors (P=
      0.0364). CONCLUSIONS: Although surgical outcomes in patients with HCC accompanied
      by MPVTT are unsatisfactory, some patients do enjoy longterm survival. When the
      number of recurrent nodules is less than four, local therapy should be selected
      with the aim of achieving 5-year survival.

PMID- 22404265
TI  - Meta-analysis of phase III randomized trials of molecular targeted therapies for
      advanced pancreatic cancer.
AB  - OBJECTIVES: For patients with unresectable pancreatic cancer (PC), the efficacy
      and safety of molecular targeted agents (MTAs) in combination with gemcitabine
      are still unclear. Published randomized controlled trials (RCTs) have reported
      conflicting results. This study aimed to conduct a systematic review of the
      literature and to perform a meta-analysis if appropriate. METHODS: Seven
      electronic databases were searched using a standard technique to November 2011
      without restriction on publication status or language. The primary aim was to
      assess overall survival (OS). Secondary aims were to assess progression-free
      survival (PFS), overall response rates (ORRs) and grade 3, 4 and 5 toxicities. A
      random-effects model was used for the meta-analysis. RESULTS: Seven Phase III
      RCTs were identified; 1981 patients were treated with MTAs and gemcitabine, and
      1992 patients received gemcitabine with or without placebo. No statistically
      significant difference in OS was found between the two groups [hazard ratio (HR)
      = 0.93, 95% confidence interval (CI) 0.85-1.02; P = 0.13]. The addition of MTAs
      improved PFS (HR = 0.86, 95% CI 0.79-0.93; P = 0.000) and ORR (odds ratio 1.35,
      95% CI 1.05-1.74; P = 0.01). However, these benefits were accompanied by
      significantly higher toxicity (P = 0.001). CONCLUSIONS: The findings of this
      study suggest that the palliation of PC with gemcitabine and MTAs does not
      provide a significant survival benefit and is associated with increased grade 3
      and 4 toxicities.

PMID- 22404266
TI  - All cholecystectomy specimens must be sent for histopathology to detect
      inapparent gallbladder cancer.
AB  - OBJECTIVES: Traditionally, a gallbladder removed for presumed benign disease has
      been sent for histopathological examination (HPE), but this practice has been the
      subject of controversy. This study was undertaken to compare patients in whom
      gallbladder cancer (GBC) was diagnosed after cholecystectomy on HPE with GBC
      patients in whom the gallbladder was not sent for HPE and who therefore presented
      late with symptoms. METHODS: A retrospective analysis of prospectively collected
      data for 170 GBC patients diagnosed after cholecystectomy was conducted. All
      patients presented to one centre during 2000-2011. These patients were divided
      into two groups based on the availability of histopathology reports: Group A
      included patients who presented early with HPE reports (n = 93), and Group B
      comprised patients who presented late with symptoms and without HPE reports (n =
      77). RESULTS: The median time to presentation in Group A was significantly lower
      than in Group B (29 days vs. 152 days; P < 0.001). Signs or symptoms suggestive
      of recurrence (pain, jaundice or gastric outlet obstruction) were present in four
      (4.3%) patients in Group A and all (100%) patients in Group B (P < 0.001).
      Patients deemed operable on preoperative evaluation included all (100%) patients
      in Group A and 38 (49.4%) patients in Group B (P < 0.0001). The overall
      resectability rate (69.9% vs. 7.8%) and median survival (54 months vs. 10 months)
      were significantly higher in Group A compared with Group B (P < 0.0001).
      CONCLUSIONS: Patients in whom a cholecystectomy specimen was sent for HPE
      presented early, had a better R0 resection rate and longer overall survival.
      Hence, routine HPE of all cholecystectomy specimens should be performed.

PMID- 22404267
TI  - All-in-one sleeve patch graft venoplasty for multiple hepatic vein reconstruction
      in living donor liver transplantation.
AB  - OBJECTIVES: This paper presents an innovative technique to address complex
      multiple hepatic vein (HV) reconstruction in right lobe graft living donor liver
      transplantation (RL-LDLT). METHODS: A patient with hepatitis C virus-related
      cirrhosis underwent RL-LDLT. The graft had seven HVs, including: the right HV (17
      mm); one segment VII HV (11 mm); two segment VI HVs (6 mm and 16 mm), and three
      segment V HVs. The graft weighed 663 g (53% of standard liver volume; ratio of
      graft weight to recipient body weight: 0.96). Each HV had significant drainage
      territory requiring reconstruction. A cryopreserved iliac vein graft was used to
      create a sleeve patch to incorporate the HV openings. The holes were anastomosed
      to their corresponding HV tributaries using continuous 6-0 polydioxanone (PDS)
      sutures. Two of the three segment V HVs were combined using a smaller iliac vein
      patch, which was anastomosed in an end-to-side fashion to a previously harvested
      recipient umbilical vein interposition graft. The other end of the umbilical vein
      graft was anastomosed to the larger iliac vein sleeve patch. RESULTS: Overall,
      six HV openings were incorporated in one sleeve patch to allow a single wide
      anastomosis with the recipient inferior vena cava. Doppler ultrasound after
      reconstruction showed adequate flow patterns in all the HVs. CONCLUSIONS: All-in
      one sleeve patch graft venoplasty simplifies the reconstruction of multiple HVs
      and reduces warm ischaemia time in RL-LDLT with excellent outcomes.

PMID- 22404268
TI  - Warshaw's technique: what's the point?

PMID- 22404271
TI  - Persistent intracellular pathogens.

PMID- 22404272
TI  - An unparalleled engine for discovery and clinical introduction: the clinical and
      translational science awards and gene therapy.

PMID- 22404274
TI  - Phosphorus net absorption in dairy cows subjected to abomasal infusion of
      inorganic phosphorus--a pilot study.
AB  - In this pilot study, the effects of phosphorus (P) supply on inorganic phosphorus
      (Pi ) net absorption in dairy cows were investigated. Three non-lactating, non
      pregnant, rumen-fistulated Swedish Red breed dairy cows were studied in a 3 * 3
      Latin square design. Monosodium dihydrogen orthophosphate dihydrate (NaH2 PO4
      *2H2 O) was continuously infused into the abomasum for 4 days. The solutions
      provided 0, 14.4 or 28.8 g Pi /day. Rumen fluid volume and outflow rate were
      estimated at day four of each experimental period using cobalt-lithium EDTA as an
      external marker. Acid insoluble ash in feeds and faecal samples was used to
      quantify P faecal excretion. Concentrations of Pi in collected samples of rumen
      fluid, blood, faeces and urine were determined. Pi flow into the small intestine
      increased (p < 0.05) with Pi infusion. Pi net absorption tended to increase (p =
      0.08) but proportion of absorbed Pi tended to decrease (p = 0.08). Urinary Pi
      excretion was negligible and did not affect P homoeostasis (p = 0.50). There was
      no change in plasma Pi concentration (p = 0.45) in response to Pi infusion. The
      increase in total faecal P excretion (p < 0.05) with increasing level of infused
      Pi was solely because of increased soluble faecal Pi (p < 0.05). It is suggested
      that at P overfeeding, intestinal Pi net absorption is saturable in dairy cows.

PMID- 22404275
TI  - Predictors of statin-induced regression of left anterior descending coronary
      artery wall thickness as measured by high-resolution transthoracic
      echocardiography.
AB  - BACKGROUND: Statin therapy has been shown to reduce cardiovascular risk after
      myocardial infarction (MI). Using a novel technique of high-resolution
      transthoracic echocardiography (HRTTE), we sought to assess the statin-induced
      changes in left anterior descending coronary artery (LAD) wall thickness in
      previously statin naive patients over a 12-month period. METHOD AND RESULTS:
      Thirty subjects underwent HRTTE assessment of their LAD wall thickness
      predischarge post-MI (non-LAD territory) and at 3, 6, and 12 months. The LAD
      anterior and posterior wall thickness and vessel luminal diameter were measured.
      Blood lipid levels were also assessed at each study visit. All subjects were
      started on moderate lipid-lowering therapy (40 mg of atorvastatin or
      simvastatin). There was a sustained decrease in total cholesterol (-23%),
      triglycerides (-19%), and low-density lipoprotein (-41%) at the 3-month visit
      from the baseline, with no change in high-density lipoprotein level. Overall,
      there was no change in the LAD wall thickness and external or vessel lumen
      diameter over the 12-month period. Of those that demonstrated regression, the
      only predictor of percentage change in the LAD wall thickness was the baseline
      LAD wall thickness. CONCLUSION: Despite a favorable change in blood lipid
      profile, no overall change in the LAD wall thickness was detected over a 12-month
      period in subjects on moderate statin therapy using HRTTE. However, using case
      based analysis, regression was able to be predicted by the baseline LAD wall
      thickness. HRTTE may be an instructive noninvasive modality to assess response to
      statin intervention.

PMID- 22404276
TI  - A newly developed scavenging system for administration of nitrous oxide during
      labour: safe occupational use.
AB  - OBJECTIVE: Nitrous oxide (N(2) O) is routinely used as an analgesic in obstetrics
      during labour. Epidemiological studies have linked chronic occupational exposure
      to N(2) O to specific health problems, including reproductive risks. Occupational
      exposure limits (OELs) allow the use of N(2) O once appropriate preventive and
      safety measures have been taken. We assessed the effectiveness of a scavenger
      system (Anevac P-system(r), Medicvent Heinen & Lowestein Benelux, Barneveld, the
      Netherlands) applied in N(2) O administration during labour in a midwifery-led
      birthing centre in the Netherlands. METHODS: After informed consent, non-pregnant
      midwives were trained to administer N(2) O. N(2) O was delivered as a 50 : 50
      mixture with oxygen and was self administered by the patient. The scavenging
      device, containing a double mask and a chin mask, was connected to the local
      evacuation system vented outside the building. Data on the 8-h time-weighted
      average (8-h TWA) as well as the 15-min TWA (15-min TWA) were obtained. RESULTS:
      Thirteen patients were included. Six patients were included in the first study
      period. In this period the 8-h TWA was not exceeded, however, in all patients,
      the 15-min TWA occasionally exceeded the OELs. After four additional measures,
      seven patients were included. After implementation of these measures, the 8-h TWA
      and 15-min TWA never exceeded the OELs. System leakage was not observed during
      both study periods. CONCLUSION: The Anevac P-scavenging system during N(2) O
      analgesia in labour prevents exceeding OELs in professional workers. The
      scavenging system appeared acceptable and effective, and can be considered in
      hospital settings that use N(2) O as analgesic during labour.

PMID- 22404277
TI  - Drug treatment and the conditionality of HIV treatment access: a qualitative
      study in a Russian city.
AB  - AIMS: We explored social factors affecting access to antiretroviral HIV treatment
      (ART) among people who inject drugs (PWID) in a Russian city with a large HIV
      burden. DESIGN: Qualitative interview study. SETTING: Community settings in
      Ekaterinburg, Russian Federation. PARTICIPANTS: 42 PWID living with HIV and 11
      health practitioners. MEASUREMENTS: Thematic analyses of in-depth qualitative
      interviews. FINDINGS: Access to ART was felt by participants to be contingent
      upon their capacity to demonstrate a commitment to becoming 'drug free'. We
      identify, across interview accounts, a treatment access narrative of 'treat drugs
      before HIV'. This narrative is upheld by ART providers' concerns to maximize
      clinical outcome in the face of adherence doubts, as well as by would-be
      patients' perceptions of expectations placed upon them by the treatment system
      and their own doubts regarding treatment engagement. This has the effect of
      reproducing a habit of ART delay and disengaging people from the treatment
      system. Difficulties accessing ART, and the perceived rationing of treatment on
      account of untreated drug use, were experienced as 'moral discipline' for falling
      short of treatment 'deservedness'. Participants describe a 'Catch 22' system,
      where they are invited to treat their drug use in a setting where effective drug
      treatment was perceived as unavailable. CONCLUSIONS: Inadequate drug treatment
      practices act as structural obstacles to realizing HIV treatment. Evidence
      internationally suggests that effective drug treatment, including opioid
      substitution therapy, improves access and adherence to antiretroviral treatment
      among people who inject drugs. Policy shifts are urgently needed in this setting
      to enable systemic improvements to drug treatment, especially given large HIV
      treatment demand.

PMID- 22404278
TI  - We are all in this together: working towards a holistic understanding of self
      harm.
AB  - Self-harm is a widespread and controversial issue in contemporary society.
      Statistics are based on reported incidents and therefore do not accurately reveal
      prevalence, as self-harm is often a hidden behaviour. This highlights the
      essential need for practitioners and society to work towards reducing the stigma
      surrounding self-harm. This paper goes some way towards understanding the impact
      of self-harm on individuals and communities. It begins by exploring terminologies
      and definitions of self-harm and discusses the importance of sensitivity in
      language use relating to self-harm. It continues by examining types of self-harm
      and subsequently presents life experiences that may contribute to the onset of
      self-harm. The paper elucidates the cultural, historical and religious origins of
      self-harm, indicating the ways in which self-harm has evolved with us as part of
      our humanity. Moreover, literature relating to the significance of stigma and
      attitudes is examined, followed by issues around psychiatric diagnoses pertaining
      to self-harm. The paper concludes by synthesizing literature relevant to the
      relationship between self-harm and suicide.

PMID- 22404280
TI  - Trend, client profile and surgical features of vasectomy in Ghana.
AB  - OBJECTIVE: To examine the socio-demographic and reproductive characteristics of
      vasectomy acceptors and surgical features of vasectomy in Ghana. METHODS:
      Retrospective review of 271 vasectomies performed between 1 January 2000 and 31
      December 2009 in three healthcare facilities. RESULTS: Less than 0.5% of family
      planning clients opt for vasectomy in Ghana; acceptors are both professional and
      semi-skilled workers. The mean age of vasectomy acceptors was 40.7 years, and
      their mean number of children four. All clients had two children or more; there
      was a trend towards a greater number of children with increasing age (p trend
      <0.001) or a lower educational level of the clients (p trend =0.01). Most clients
      obtained their information on vasectomy through the media and healthcare workers.
      Nearly all vasectomies were performed under local anaesthesia using the no
      scalpel technique. The operating time of gynaecologists was significantly shorter
      than that of urologists (median operating time 10 minutes vs. 25 minutes; p
      <0.001). The reported vasectomy failure rate was about 1%. CONCLUSIONS: The
      prevalence of vasectomy is low in Ghana. The factors influencing utilisation of
      male sterilisation services must be identified in order to improve uptake of this
      method of contraception in the country.

PMID- 22404281
TI  - Climate change, indoor environments, and health.

PMID- 22404282
TI  - Cerebral vascular effects of hypovolemia and dopamine infusions: a study in
      newborn piglets.
AB  - AIM: Despite widespread use, effects of volume boluses and dopamine in
      hypotensive newborn infants remain controversial. We aimed to elucidate if
      hypovolemia alone impairs cerebral autoregulation (CA) and if dopamine affects
      cerebral vasculature. METHODS: In 12 piglets, cerebral perfusion (laser-Doppler
      flux) and oxygenation [near-infrared spectroscopy (NIRS)] were examined during
      dopamine (20-50 MUg/kg per minute) and nonpharmacologically induced blood
      pressure (ABP) changes. Effect on cerebral perfusion and oxygenation was
      quantified as frequency gain between ABP and laser-Doppler flux (gain-LDF) and
      NIRS [gain-oxygenation index (OI)], respectively. Gain quantifies change in
      perfusion or oxygenation per ABP-change. CA was estimated as gain-LDF during
      nonpharmacologically induced ABP changes, that is, as degree of impairment.
      Dopamine's cerebrovascular effect was estimated by contrasting gain during
      dopamine- and nonpharmacologically induced ABP changes. Measurements were
      conducted during both normovolemia- and haemorrhage-induced hypovolemia. RESULTS:
      Hypovolemia elicited hypotension (p = 0.02) as well as increasing impairment of
      CA (p = 0.01). However, hypovolemia without hypotension did not affect CA
      significantly. Dopamine increased perfusion significantly compared to
      nonpharmacological challenges (mean difference: 1.5%/mmHg, 95% CI: 0.5-2.6, p =
      0.007). Oxygenation was, however, similar (mean difference: 0.01 MUmol/L per
      mmHg, 95% CI: -0.03 to 0.05, p = 0.7). CONCLUSION: Our findings do not support
      that hypovolemia alone impairs CA. Furthermore, dopamine seems to increase
      cerebral perfusion but not oxygenation.

PMID- 22404283
TI  - Lithographically defined three-dimensional graphene structures.
AB  - A simple and facile method to fabricate 3D graphene architectures is presented.
      Pyrolyzed photoresist films (PPF) can easily be patterned into a variety of 2D
      and 3D structures. We demonstrate how prestructured PPF can be chemically
      converted into hollow, interconnected 3D multilayered graphene structures having
      pore sizes around 500 nm. Electrodes formed from these structures exhibit
      excellent electrochemical properties including high surface area and steady-state
      mass transport profiles due to a unique combination of 3D pore structure and the
      intrinsic advantages of electron transport in graphene, which makes this material
      a promising candidate for microbattery and sensing applications.

PMID- 22404284
TI  - Symmetrical analysis of risk-benefit.
AB  - To quantify the value of a medical therapy the benefits are weighed against the
      risks. Effectiveness is defined by objective evidence from predefined endpoints.
      This benefit is offset against the disadvantage of adverse events. The safety
      assessment is usually a subjective summary of concerns that can often be neither
      confirmed nor dismissed. But sometimes a clinical database is so large that a
      parameter common to both efficacy and safety can be quantified with reasonable
      certainty: myocardial infarction (MI) is used here as an example. Recently the
      Food and Drug Administration (FDA) proposed set limits for the incidence of MI as
      a safety threshold for diabetes treatment. Setting a threshold before something
      is considered as a safety concern opens the possibility of setting a threshold
      for clinically important efficacy. When a parameter is common to both safety and
      efficacy, then logically a unit change in either direction should be of equal
      weight in the risk and benefit analysis. For example, a doubling in the incidence
      of myocardial infarction as a safety signal should be given equal weight to the
      halving of the incidence of myocardial infarction as an efficacy signal.
      Similarly, if FDA guidance suggests that a less than a 30% increase in the
      incidence of MI as a safety parameter is considered acceptable, for example for
      diabetes treatment, when there is no other major toxicity, this opens a debate
      about a possible inverse threshold for clinical benefit for drugs that reduce a
      risk factor, such as antihypertensives.

PMID- 22404285
TI  - On statistical methods to test if sampling in trials is genuinely random.

PMID- 22404286
TI  - Transport properties investigation of aqueous protic ionic liquid solutions
      through conductivity, viscosity, and NMR self-diffusion measurements.
AB  - We present a study on the transport properties through conductivity (sigma),
      viscosity (eta), and self-diffusion coefficient (D) measurements of two pure
      protic ionic liquids--pyrrolidinium hydrogen sulfate, [Pyrr][HSO(4)], and
      pyrrolidinium trifluoroacetate, [Pyrr][CF(3)COO]--and their mixtures with water
      over the whole composition range at 298.15 K and atmospheric pressure. Based on
      these experimental results, transport mobilities of ions have been then
      investigated in each case through the Stokes-Einstein equation. From this, the
      proton conduction in these PILs follows a combination of Grotthuss and vehicle
      type mechanisms, which depends also on the water composition in solution. In each
      case, the displacement of the NMR peak attributed to the labile proton on the
      pyrrolidinium cation with the PILs concentration in aqueous solution indicates
      that this proton is located between the cation and the anion for a water weight
      fraction lower than 8%. In other words, for such compositions, it appears that
      this labile proton is not solvated by water molecules. However, for higher water
      content, the labile protons are in solution as H(3)O(+). This water weight
      fraction appears to be the solvation limit of the H(+) ions by water molecules in
      these two PILs solutions. However, [Pyrr][HSO(4)] and [Pyrr][CF(3)COO] PILs
      present opposed comportment in aqueous solution. In the case of [Pyrr][CF(3)COO],
      eta, sigma, D, and the attractive potential, E(pot), between ions indicate
      clearly that the diffusion of each ion is similar. In other words, these ions are
      tightly bound together as ion pairs, reflecting in fact the importance of the
      hydrophobicity of the trifluoroacetate anion, whereas, in the case of the
      [Pyrr][HSO(4)], the strong H-bond between the HSO(4)(-) anion and water promotes
      a drastic change in the viscosity of the aqueous solution, as well as on the
      conductivity which is up to 187 mS.cm(-1) for water weight fraction close to 60%
      at 298 K.

PMID- 22404287
TI  - Needs of adult family members of intensive care unit patients.
AB  - AIMS AND OBJECTIVES: The purpose of this research was to examine current
      perceptions of adult family members' needs of intensive care unit patients in the
      Midwest, USA. Examining family needs may help determine effectiveness of
      guideline implementation. BACKGROUND: Family needs of intensive care unit
      patients is a topic widely researched, but to date, the application of that
      research to the clinical practice guidelines is limited. Family members' of
      intensive care unit patients often experience stress and anxiety because of the
      high mortality rate of patients in intensive care. Family members are often
      involved with the patient's care especially as many units have open visitation
      policies. DESIGN: Survey. METHOD: The Critical Care Family Needs Inventory was
      distributed to a convenience sample of 50 family members from a Central Illinois,
      not-for-profit, 22-bed intensive care unit in the USA. RESULTS: Forty-five adult
      family members returned completed questionnaires. The majority of the sample was
      female (66.7%), 40% were 49-64 years old. The majority of the sample of family
      members was spouses (36%) or adult children (36%). Eighty per cent of these
      family members reported they had previously visited a patient in the intensive
      care unit. Results of the survey revealed family members perceived assurance as
      the highest needs categories and support as the least important need.
      CONCLUSIONS: Findings were consistent with earlier studies identifying assurance
      as a very important need. After publication of clinical practice guidelines for
      support of the family in the patient-centred intensive care unit, families
      continue to report the need for assurance. RELEVANCE TO CLINICAL PRACTICE: Nurses
      need to give increased attention to effectively implementing clinical practice
      guidelines in an effort to meet family members' needs, especially those related
      to assurance. Assurance may be expressed differently by various cultures.

PMID- 22404289
TI  - Plasmonic nanopowders for photothermal therapy of tumors.
AB  - We describe a novel strategy for the fabrication of plasmonic nanopowders (dried
      gold nanoparticles) by using wet chemical nanoparticle synthesis, PEG-SH
      functionalization, and a standard freeze-drying technique. Our strategy is
      illustrated by successful fabrication of different plasmonic nanopowders,
      including gold nanorods, gold-silver nanocages, and gold nanospheres.
      Importantly, the dried nanoparticles can be stored for a long time under usual
      conditions and then can easily be dissolved in water at a desired concentration
      without such hard manipulations as sonication or heating. Redispersed samples
      maintain the plasmonic properties of parent colloids and do not form aggregates.
      These properties make pegylated freeze-dried gold nanoparticles attractive
      candidates for plasmonic photothermal therapy in clinical settings. In this work,
      redispersed gold nanorods were intravenously administered to mice bearing Ehrlich
      carcinoma tumors at doses of 2 and 8 mg (Au)/kg (animal). Particle
      biodistribution was measured by atomic absorption spectroscopy, and tumor
      hyperthermia effects were studied under laser NIR irradiation. Significant tumor
      damage was observed only at the higher dose of the nanorods.

PMID- 22404290
TI  - Annual research review: functional somatic symptoms and associated anxiety and
      depression--developmental psychopathology in pediatric practice.
AB  - BACKGROUND: Medically unexplained physical symptoms, commonly referred to as
      functional somatic symptoms (FSS), are common in pediatric medical settings and
      associated with suffering, impairment, and medical help seeking. The association
      of pediatric FSS with anxiety and depressive symptoms and disorders across the
      life span is reviewed. METHOD: Review and critique of controlled studies
      examining cross-sectional and longitudinal associations of FSS with anxiety and
      depressive symptoms and disorders in community-based and clinical samples of
      children and adolescents. RESULTS: FSS are consistently associated cross
      sectionally with anxiety and depressive symptoms and disorders in childhood and
      adolescence, and the likelihood of associated anxiety and depression increases
      with the number of reported FSS. The presence of one or more FSS early in life is
      associated with an increased likelihood of multiple FSS and anxiety and
      depressive symptoms and disorders later in life, and anxiety and depressive
      symptoms and disorders in childhood are associated with subsequent multiple FSS.
      CONCLUSION: Strong associations between FSS, anxiety, and depression across the
      life span suggest the need to reconsider existing nosology and reconceptualize
      symptomatic relationships. Large, population-based longitudinal studies of FSS,
      anxiety, and depressive symptoms and disorders are needed to establish temporal
      relationships between the various symptoms and conditions.

PMID- 22404288
TI  - DNA replication fidelity in Escherichia coli: a multi-DNA polymerase affair.
AB  - High accuracy (fidelity) of DNA replication is important for cells to preserve
      the genetic identity and to prevent the accumulation of deleterious mutations.
      The error rate during DNA replication is as low as 10(-9)  to 10(-11)  errors per
      base pair. How this low level is achieved is an issue of major interest. This
      review is concerned with the mechanisms underlying the fidelity of the
      chromosomal replication in the model system Escherichia coli by DNA polymerase
      III holoenzyme, with further emphasis on participation of the other, accessory
      DNA polymerases, of which E. coli contains four (Pols I, II, IV, and V). Detailed
      genetic analysis of mutation rates revealed that (1) Pol II has an important role
      as a back-up proofreader for Pol III, (2) Pols IV and V do not normally
      contribute significantly to replication fidelity, but can readily do so under
      conditions of elevated expression, (3) participation of Pols IV and V, in
      contrast to that of Pol II, is specific to the lagging strand, and (4) Pol I also
      makes a lagging-strand-specific fidelity contribution, limited, however, to the
      faithful filling of the Okazaki fragment gaps. The fidelity role of the Pol III
      tau subunit is also reviewed.

PMID- 22404291
TI  - Expression of the vitamin D metabolizing enzyme CYP24A1 at the annulus of human
      spermatozoa may serve as a novel marker of semen quality.
AB  - Vitamin D (VD) is important for male reproduction in mammals and the VD receptor
      (VDR) and VD-metabolizing enzymes are expressed in human spermatozoa. The VD
      inactivating enzyme CYP24A1 titrates the cellular responsiveness to VD, is
      transcriptionally regulated by VD, and has a distinct expression at the sperm
      annulus. Here, we investigated if CYP24A1 expression serves as a marker for VD
      metabolism in spermatozoa, and whether CYP24A1 expression was associated with
      semen quality. We included 130 men (53 healthy young volunteers and 77 subfertile
      men) for semen analysis and immunocytochemical (ICC) detection of CYP24A1.
      Another 40 men (22 young, 18 subfertile) were tested for in vitro effects of
      1,25(OH)(2)D(3) on intracellular calcium concentration ([Ca(2+)](i)) and sperm
      motility. Double ICC staining showed that CYP24A1 and VDR were either
      concomitantly expressed or absent in 80% of the spermatozoa from young men. The
      median number of CYP24A1-expressing spermatozoa was 1% in subfertile men and thus
      significantly (p < 0.0005) lower than 25% in spermatozoa from young men.
      Moreover, CYP24A1 expression correlated positively with total sperm count, 
      concentration, -motility and -morphology (all p < 0.004), and the percentage of
      CYP24A1-positive spermatozoa increased (15 vs. 41%, p < 0.0005) after percoll
      gradient-centrifugation. We noticed that the presence of >3% CYP24A1-positive
      spermatozoa distinguished young men from subfertile men with a sensitivity of
      66.0%, a specificity of 77.9% and a positive predictive value of 98.3%.
      Functional studies revealed that 1,25(OH)(2)D(3) increased [Ca(2+)](i) and sperm
      motility in young healthy men, while 1,25(OH)(2)D(3) was unable to increase
      motility in subfertile patients. In conclusion, we suggest that CYP24A1
      expression at the annulus may serve as a novel marker of semen quality and an
      objective proxy for sperm function.

PMID- 22404292
TI  - Coronary flow reserve in patients with diabetes mellitus and prediabetes.
AB  - BACKGROUND: Abnormalities of coronary microcirculation have been reported in
      patients with diabetes mellitus (DM) even in the presence of normal coronary
      arteries. It is unknown when the microvascular effects on coronary arteries begin
      to appear in the DM disease course. Coronary flow reserve (CFR), determined by
      pharmacological stress transthoracic Doppler echocardiography, is a reliable
      indicator of coronary microvascular function. We sought to determine the coronary
      microvascular function of prediabetic patients compared to DM patients and normal
      population. METHODS: Seventy-four subjects with normal coronary arteries were
      enrolled. DM and prediabetes were diagnosed according to American Diabetes
      Association criteria. All subjects had Doppler recordings of the left anterior
      descending artery with adenosine infusion at a rate of 0.014 mg/kg per minute.
      RESULTS: The demographical characteristics and laboratory findings of the three
      groups were similar (DM group: n = 25, mean age 62 +/- 7 years, 19 females;
      prediabetic group: n = 25, mean age 64 +/- 12 years, 21 females; control group: n
      = 24, mean age 63 +/- 7 years, 15 females) except fasting glucose levels. CFR
      values of the three groups were significantly different (DM group: CFR = 1.75 +/-
      0.50; prediabetic group: CFR = 2.24 +/- 0.43; control group: CFR = 2.38 +/- 0.32,
      P < 0.001). CFR values of DM group were lower than those of prediabetic and
      control groups (DM vs. prediabetic: P < 0.001, DM vs. control: P < 0.001).
      However, CFR levels of prediabetic group were not different from those of the
      control group (P = 0.481). DM was an independent factor predictive of CFR < 2
      (OR, 22.69; 95% CI, 6.47-79.51; P < 0.001). CONCLUSION: Coronary microvascular
      function seems to be normal in the prediabetic state, but dysfunction appears
      after DM becomes overt.

PMID- 22404293
TI  - Ear and electrode effects reduce within-group variability in middle latency
      response amplitude measures.
AB  - OBJECTIVES: To establish normative amplitude values for relative difference
      measurements of the middle latency response (MLR) in normal-hearing pediatrics
      and to determine if these measurements provided a significant reduction of within
      group variability when compared to raw, absolute amplitude measures. A relative
      amplitude difference is defined in the present paper as the difference in Na-Pa
      amplitude between two electrodes (e.g. |Na-Pa at C3 minus Na-Pa at C4|, or
      electrode effects) or between two ears (e.g. |Na-Pa on left ear stimulation minus
      Na-Pa on right ear stimulation|, or ear effects). In contrast, an absolute
      amplitude is defined as a single Na-Pa measurement made at one electrode for
      stimulation of one ear (e.g. Na-Pa measured at C3 on left ear stimulation).
      DESIGN: Cross-sectional study. STUDY SAMPLE: 155 pediatrics with normal
      peripheral and central hearing, and no history of psychological, neurological, or
      learning disability issues. RESULTS: Within-group variability was significantly
      smaller for relative differences when compared to absolute amplitude measures.
      Electrode effects showed significantly less variability than ear effects.
      Normative values for ear and electrode effects were reported. CONCLUSIONS:
      Relative differences may provide better utility in the clinical diagnosis of
      central auditory pathology in pediatrics when compared to absolute amplitude
      measures because these difference measures show significantly lower variability
      when examined across subjects.

PMID- 22404294
TI  - Burnout and quality of life among Spanish healthcare personnel.
AB  - The purpose of this study was to analyse the relationship between perceived
      quality of life and levels of burnout among healthcare personnel. A sample of
      1095 participants (nurses, physicians, nursing assistants and orderlies) from
      five hospitals in the province of Girona (Spain) were studied (78% women, mean
      age=36.6 years, SD=8.8) using the 36-item short-form health questionnaire (SF-36)
      and the Maslach Burnout Inventory. The results showed that health-related quality
      of life reported by this sample of healthcare personnel was lower than the
      reference population values, especially in those SF-36 dimensions that comprise
      the mental component. In comparing the dimensions of the SF-36 by profession, we
      found that physicians had better perceived health in the dimensions of the
      physical component than nurses and other professionals (P< 0.01). No statistical
      differences were observed between profession and the dimensions of the mental
      component (P>0.05). Moreover, perceived health was worse among those that
      reported a high level on any of the components of burnout. These results should
      be taken account when designing a burnout prevention programme in the workplace.

PMID- 22404295
TI  - Comparison of two exhaled nitric oxide analyzers: the NIOX MINO hand-held
      electrochemical analyzer and the NOA280i stationary chemiluminescence analyzer.
AB  - BACKGROUND AND OBJECTIVE: Measurement of the fraction of nitric oxide (FeNO) in
      exhaled air is useful in the management of asthma. A new hand-held nitric oxide
      (NO) analyzer, the NIOX MINO, is simple and easy to use in clinical practice. In
      this study, FeNO values measured using the NIOX MINO were compared with those
      obtained using a stationary chemiluminescence analyzer, the Sievers NOA280i.
      METHODS: FeNO was measured in 100 adults, using both the NIOX MINO and the
      NOA280i. Nine (9.0%) of these subjects had asthma. The first acceptable
      measurement with the NIOX MINO and the mean of two acceptable measurements with
      the NOA280i were compared. RESULTS: There was a significant correlation between
      FeNO concentrations measured with the two devices (r = 0.876, P < 0.001). A Bland
      Altman plot showed a high degree of agreement between the two devices: the mean
      inter-device difference was 3.3 parts per billion (ppb), and the 95% limits of
      agreement were -7.0 and 13.6 ppb. In addition, the mean relative difference was
      14.5%, with the 95% limits of agreement being -33.7 and 62.7%. The mean value (+/
      standard error of the mean) for FeNO as measured with the NIOX MINO (18.8 +/-
      0.9 ppb) was significantly lower than that measured with the NOA280i (22.1 +/-
      1.2 ppb, P < 0.001). CONCLUSIONS: There was a significant correlation, but only
      moderate agreement, between FeNO values measured with the NIOX MINO and those
      measured with the NOA280i, with the NIOX MINO values being significantly lower
      than the NOA280i values. Significant differences in FeNO values obtained with
      these two NO analyzers should be considered when interpreting the results of FeNO
      measurements.

PMID- 22404296
TI  - Cheek advancement flap with retained standing cone for reconstruction of a defect
      involving the upper lip, nasal sill, alar insertion, and medial cheek.

PMID- 22404297
TI  - New hypothesis of chronic back pain: low pH promotes nerve ingrowth into damaged
      intervertebral disks.
AB  - The pathogenesis of low back pain is still elusive. Here, we proposed a new
      hypothesis that low pH is a possible cause of the development and progression of
      low back pain. We propose that low pH promotes the production of the inflammatory
      mediators and the depletion of proteoglycan in the damaged intervertebral disk.
      The inflammation response, evoked by the dorsal root ganglia, changes the
      delicate nutrient balance in the nucleus, resulting in a vicious cycle and
      leading to choronic back pain. Our hypothesis may explain many of the available
      clinical and experimental data on low back pain, thus it may help elucidate the
      pathogenesis of low back pain and improve clinical management.

PMID- 22404298
TI  - Editorial update on emerging treatments of atopic dermatitis.
AB  - Various new agents are in the research pipeline for atopic dermatitis. These
      include IL-4 receptor antagonist, cis-urocanic acid, kappa-opiod receptor
      agonist, neurokinin receptor antagonist and antimicrobial peptide. The current
      review updates the status of these clinical trials and provides insight into
      other potential molecular targets including IL-22 and TLR-2.

PMID- 22404299
TI  - The culturable bacterial community of frass produced by larvae of Rhynchophorus
      ferrugineus Olivier (Coleoptera: Curculionidae) in the Canary island date palm.
AB  - AIMS: Larvae of the red palm weevil (RPW) Rhynchophorus ferrugineus Olivier
      (Coleoptera: Curculionidae) feed inside palm stem tissues, making galleries and
      producing a wet fermenting frass. We characterized the culturable bacteria
      associated with frass produced by tunnelling larvae inside the Canary island date
      palms and investigated the role of frass and gut bacteria in plant polymers
      breakdown. METHODS AND RESULTS: A culture-dependent method was used to isolate
      bacteria from frass and noninfested palm tissues. Bacterial isolates were grouped
      into operational taxonomic units based on polymorphisms in the ITS-PCR profiles,
      and representative isolates were identified by partial sequencing of the 16S rRNA
      gene. Frass bacteria were dominated by 2,3-butanediol fermenter
      Enterobacteriaceae. None of the bacterial isolates was able to degrade cellulose;
      however, cellulolytic and hemicellulolytic bacteria were isolated from the larval
      gut enrichment cultures. CONCLUSIONS:   Frass bacteria are specifically
      associated with the RPW larvae and might play beneficial roles for RPW, other
      than nutritional, that deserve further investigations. Breakdown of plant
      polymers probably occurs inside the larvae digestive system. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Frass and gut micro-organisms of R. ferrugineus should be
      included in studies of the interactions between RPW, its plant hosts, and its
      enemies.

PMID- 22404300
TI  - MDMA and 5-HT neurotoxicity: the empirical evidence for its adverse effects in
      humans - no need for translation.
AB  - In this issue of the BJP, Green et al. suggest that animal data could not be used
      to predict the adverse effects of 3,4-methylenedioxymethamphetamine (MDMA) in
      humans and that MDMA did not produce 5-HT neurotoxicity in the human brain. This
      proposal was, however, not accompanied by a review of the empirical evidence in
      humans. The neuroimaging data on 5-HT markers in abstinent recreational
      ecstasy/MDMA users are extensive and broadly consistent. Reduced levels of the 5
      HT transporter (SERT) have been found by research groups worldwide using a
      variety of assessment measures. These SERT reductions occur across the higher
      brain regions and remain after controlling for potential confounds. There are
      also extensive empirical data for impairments in memory and higher cognition,
      with the neurocognitive deficits correlating with the extent of SERT loss. Hence,
      MDMA is clearly damaging to humans, with extensive empirical data for both
      structural and functional deficits.

PMID- 22404301
TI  - Synthesis and discovery of N-carbonylpyrrolidine- or N-sulfonylpyrrolidine
      containing uracil derivatives as potent human deoxyuridine triphosphatase
      inhibitors.
AB  - Recently, deoxyuridine triphosphatase (dUTPase) has emerged as a potential target
      for drug development as part of a new strategy of 5-fluorouracil-based
      combination chemotherapy. We have initiated a program to develop potent drug-like
      dUTPase inhibitors based on structure-activity relationship (SAR) studies of
      uracil derivatives. N-Carbonylpyrrolidine- and N-sulfonylpyrrolidine-containing
      uracils were found to be promising scaffolds that led us to human dUTPase
      inhibitors (12k) having excellent potencies (IC(50) = 0.15 MUM). The X-ray
      structure of a complex of 16a and human dUTPase revealed a unique binding mode
      wherein its uracil ring and phenyl ring occupy a uracil recognition region and a
      hydrophobic region, respectively, and are stacked on each other. Compounds 12a
      and 16a markedly enhanced the growth inhibition activity of 5-fluoro-2'
      deoxyuridine against HeLa S3 cells in vitro (EC(50) = 0.27-0.30 MUM), suggesting
      that our novel dUTPase inhibitors could contribute to the development of
      chemotherapeutic strategies when used in combination with TS inhibitors.

PMID- 22404302
TI  - Lateral semicircular canal plugging with endolymphatic sac decompression as new
      surgical treatment for intractable Meniere's disease.
AB  - CONCLUSION: Lateral canal plugging with endolymphatic sac decompression (LCPESD)
      is a new therapeutic approach to intractable Meniere's disease. Further clinical
      data will be required. OBJECTIVE: The objective of this paper is to present a new
      surgical procedure, i.e. lateral canal plugging (LCP) with endolymphatic sac
      decompression (ESD), which we defined as LCPESD. Two cases of intractable
      Meniere's disease, a 48-year-old male and a 48-year-old female, were successfully
      treated by this method. METHODS: LCPESD was performed under general anesthesia.
      First ESD was undertaken followed by LCP. The bone was drilled up to the 'blue
      line' in the central portion of the bony lateral canal; then a 2 mm segment of
      canal was skeletonized to create a fenestra. A plug comprising temporalis fascia,
      bone pate, and fibrinogen glue was inserted through the fenestra to compress the
      endosteum and membranous labyrinth. RESULTS: The attack of Meniere's disease was
      completely controlled and the hearing threshold did not change after the surgery
      for 2 years. Obliteration of the horizontal canal was confirmed by MRI.

PMID- 22404303
TI  - Teenage sexual attitudes and behaviour in China: a literature review.
AB  - China is the most populated of any country in the world. Social norms and values
      pertaining to love and marriage have changed considerably since the launch of its
      open-door policy and economic reforms of the 1980s. Attitudes to sex have become
      more open, while the negative consequences of early sexual intercourse have
      become issues of health and social concern. The aim of this study is to provide
      an overview of the teenage sexual attitudes and behaviour in contemporary China.
      A literature review was conducted between 2000 and 2010, using both English
      (Medline, CINAHL, PsycINFO, ASSIA) and Chinese language databases (China National
      Knowledge Infrastructure, Wanfang database). Thirty-six studies were included and
      reviewed. It was found that young people reported poor sexual knowledge,
      especially in relation to reproductive matters and sexually transmitted
      infections. The media, such as television, magazines and the Internet, were seen
      as their main sources of information on sex. Despite the frequently reported
      liberal attitudes to sexual behaviour, only a small number of young people had
      already lost their virginity or been involved in pregnancies. Young men were more
      likely than young women to report having had sex, while respondents at vocational
      high schools were less likely to remain virgins than those at common/key high
      schools. Although the prevalence of sexual intercourse among Chinese teenagers
      was still lower than that reported in studies conducted in most western
      countries, the findings do reflect some changes in sexual values and behaviour of
      young people within the country. They also suggest the need to develop more
      comprehensive sex education programmes in co-operation with young people,
      schools, health organisations, families and communities and to make sexual and
      reproductive health services accessible to teenagers and unmarried young people
      throughout China.

PMID- 22404304
TI  - Effect of quercetin and its glucuronide metabolite upon 6-hydroxydopamine-induced
      oxidative damage in Neuro-2a cells.
AB  - Quercetin is ubiquitously distributed in plant foods. This antioxidative
      polyphenol is mostly converted to conjugated metabolites in the body. Parkinson
      disease (PD) has been suggested to be related to oxidative stress derived from
      abnormal dopaminergic activity. We evaluated if dietary quercetin contributes to
      the antioxidant network in the central nervous system from the viewpoint of PD
      prevention. A neurotoxin, 6-hydroxydopamine (6-OHDA), was used as a model of PD.
      6-OHDA-induced H2O2 production and cell death in mouse neuroblastoma, Neuro-2a.
      Quercetin aglycone suppressed 6-OHDA-induced H2O2 production and cell death,
      although aglycone itself reduced cell viability at higher concentration.
      Quercetin 3-O-beta-D-glucuronide (Q3GA), which is an antioxidative metabolite of
      dietary quercetin, was little incorporated into the cell resulting in neither
      suppression of 6-OHDA-induced cell death nor reduction of cell viability. Q3GA
      was found to be deconjugated to quercetin by microglial MG-6 cells. These results
      indicate that quercetin metabolites should be converted to their aglycone to
      exert preventive effect on damage to neuronal cells.

PMID- 22404305
TI  - Effect of different blood-guided conditioning programmes on skeletal muscle
      ultrastructure and histochemistry of sport horses.
AB  - The effects of three different blood-guided conditioning programmes on
      ultrastructural and histochemical features of the gluteus medius muscle of 2-year
      old sport horses were examined. Six non-trained Haflinger horses performed three
      consecutive conditioning programmes of varying lactate-guided intensities
      [velocities eliciting blood lactate concentrations of 1.5 (v1.5 ), 2.5 (v2.5 )
      and 4 (v4 ) mm respectively] and durations (25 and 45 min). Each conditioning
      programme lasted 6 weeks and was followed by a 5-week resting period. Pre-, post-
      and deconditioning muscle biopsies were analysed. Although training and
      detraining adaptations were similar in nature, they varied significantly in
      magnitude among the three different conditioning programmes. Overall, the
      adaptations consisted in significant increases in size of mitochondria and
      myofibrils, as well as a hypertrophy of myofibrillar ATPase type IIA muscle
      fibres and a reduction in number of type IIx low-oxidative fibres. Together,
      these changes are compatible with a significant improvement in both muscle
      aerobic capacity and muscle strength. The use of v1.5 and v2.5 as the exercise
      intensities for 45 min elicited more significant adaptations in muscle, whereas
      conditioning horses at v4 for 25 min evoked minimal changes. Most of these
      muscular adaptations returned towards the pre-conditioning status after 5 weeks
      of inactivity. It is concluded that exercises of low or moderate intensities (in
      the range between v1.5 and v2.5 ) and long duration (45 min) are more effective
      for improving muscle features associated with stamina and power in sport horses
      than exercises of higher intensity (equivalent to v4 ) and shorter duration (25
      min).

PMID- 22404306
TI  - Comparison of the metabolic profiling of hepatitis B virus-infected cirrhosis and
      alcoholic cirrhosis patients by using (1) H NMR-based metabonomics.
AB  - AIM:   The aims of the present study were to depict the serum metabolic
      characteristics of hepatitis B virus (HBV)-infected cirrhosis and alcoholic
      cirrhosis patients, and to find the specific serum biomarkers associated with the
      diseases. METHODS:   A pilot metabolic profiling study was conducted using three
      groups: HBV-infected cirrhosis patients (n = 21), alcoholic cirrhosis patients (n
      = 20) and healthy controls (n = 20). (1) H nuclear magnetic resonance (NMR)-based
      metabonomics was used to obtain the serum metabolic profiles of the samples. The
      acquired data were processed by multivariate principal component analysis (PCA)
      and orthogonal partial least-squares-discriminant analysis (OPLS-DA). The
      discriminatory metabolites between HBV-infected cirrhosis and alcoholic cirrhosis
      were further validated by classical biochemical assays. RESULTS:   The OPLS-DA
      model was capable of distinguishing between HBV-infected and alcoholic cirrhosis
      patients. Five metabolites, creatine, acetoacetate, isobutyrate, glutamine and
      glutamate, were identified as the most influential factors to compare HBV
      infected cirrhosis and alcoholic cirrhosis. The validation tests showed that the
      changes of the five metabolites were well coincident with the results of NMR.
      CONCLUSION:   NMR spectra combined with pattern recognition analysis techniques
      may provide a new way to explore the pathogenesis of HBV-infected and alcoholic
      cirrhosis patients.

PMID- 22404307
TI  - Charge transport in nanoscale "all-inorganic" networks of semiconductor nanorods
      linked by metal domains.
AB  - Charge transport across metal-semiconductor interfaces at the nanoscale is a
      crucial issue in nanoelectronics. Chains of semiconductor nanorods linked by Au
      particles represent an ideal model system in this respect, because the metal
      semiconductor interface is an intrinsic feature of the nanosystem and does not
      manifest solely as the contact to the macroscopic external electrodes. Here we
      investigate charge transport mechanisms in all-inorganic hybrid metal
      semiconductor networks fabricated via self-assembly in solution, in which CdSe
      nanorods were linked to each other by Au nanoparticles. Thermal annealing of our
      devices changed the morphology of the networks and resulted in the removal of
      small Au domains that were present on the lateral nanorod facets, and in ripening
      of the Au nanoparticles in the nanorod junctions with more homogeneous metal
      semiconductor interfaces. In such thermally annealed devices the voltage
      dependence of the current at room temperature can be well described by a Schottky
      barrier lowering at a metal semiconductor contact under reverse bias, if the
      spherical shape of the gold nanoparticles is considered. In this case the natural
      logarithm of the current does not follow the square-root dependence of the
      voltage as in the bulk, but that of V(2/3). From our fitting with this model we
      extract the effective permittivity that agrees well with theoretical predictions
      for the permittivity near the surface of CdSe nanorods. Furthermore, the
      annealing improved the network conductance at cryogenic temperatures, which could
      be related to the reduction of the number of trap states.

PMID- 22404308
TI  - Quantification of the spatial distribution of rectally applied surrogates for
      microbicide and semen in colon with SPECT and magnetic resonance imaging.
AB  - AIMS: We sought to describe quantitatively the distribution of rectally
      administered gels and seminal fluid surrogates using novel concentration-distance
      parameters that could be repeated over time. These methods are needed to develop
      rationally rectal microbicides to target and prevent HIV infection. METHODS:
      Eight subjects were dosed rectally with radiolabelled and gadolinium-labelled
      gels to simulate microbicide gel and seminal fluid. Rectal doses were given with
      and without simulated receptive anal intercourse. Twenty-four hour distribution
      was assessed with indirect single photon emission computed tomography
      (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI), and direct
      assessment via sigmoidoscopic brushes. Concentration-distance curves were
      generated using an algorithm for fitting SPECT data in three dimensions. Three
      novel concentration-distance parameters were defined to describe quantitatively
      the distribution of radiolabels: maximal distance (D(max) ), distance at maximal
      concentration (D(Cmax) ) and mean residence distance (D(ave) ). RESULTS: The
      SPECT/CT distribution of microbicide and semen surrogates was similar. Between 1
      h and 24 h post dose, the surrogates migrated retrograde in all three parameters
      (relative to coccygeal level; geometric mean [95% confidence interval]): maximal
      distance (D(max) ), 10 cm (8.6-12) to 18 cm (13-26), distance at maximal
      concentration (D(Cmax) ), 3.8 cm (2.7-5.3) to 4.2 cm (2.8-6.3) and mean residence
      distance (D(ave) ), 4.3 cm (3.5-5.1) to 7.6 cm (5.3-11). Sigmoidoscopy and MRI
      correlated only roughly with SPECT/CT. CONCLUSIONS: Rectal microbicide surrogates
      migrated retrograde during the 24 h following dosing. Spatial kinetic parameters
      estimated using three dimensional curve fitting of distribution data should prove
      useful for evaluating rectal formulations of drugs for HIV prevention and other
      indications.

PMID- 22404309
TI  - A simplified method to generate serotonergic neurons from mouse embryonic stem
      and induced pluripotent stem cells.
AB  - We have developed a new simple method to induce serotonergic neurons from
      embryonic stem (ES) and induced pluripotent stem cells. When ES or induced
      pluripotent stem cells were cultured on a thick gel layer of Matrigel, most
      colonies extended TuJ1-positive neurites. We found that noggin, a known
      antagonist of bone morphogenic protein, induces ES cells to express genes
      involved in serotonergic differentiation, such as Nkx2.2, Pet-1, Sonic hedgehog,
      tryptophan hydroxylase 2, and serotonin transporter, as well as increases high
      potassium-induced release of serotonin. To concentrate serotonergic neurons, ES
      cells carrying Pet-1-enhancer-driven enhanced green fluorescent protein were
      differentiated and sorted into about 80% pure cultures of serotonergic neurons.
      Whole cell voltage-clamp recordings showed a voltage-dependent current in
      dissociated neurons. This simplified method provides an alternative option for
      serotonergic differentiation of pluripotent stem cells and will likely contribute
      a deeper understanding regarding the nature of serotonergic neurons and open new
      therapeutic perspectives for the treatment of psychiatric disorders.

PMID- 22404310
TI  - Simulating the dynamics and orientations of spin-labeled side chains in a protein
      DNA complex.
AB  - Site-directed spin labeling, wherein a nitroxide side chain is introduced into a
      protein at a selected mutant site, is increasingly employed to investigate
      biological systems by electron spin resonance (ESR) spectroscopy. An
      understanding of the packing and dynamics of the spin label is needed to extract
      the biologically relevant information about the macromolecule from ESR
      measurements. In this work, molecular dynamics (MD) simulations were performed on
      the spin-labeled restriction endonuclease, EcoRI in complex with DNA. Mutants of
      this homodimeric enzyme were previously constructed, and distance measurements
      were performed using the double electron electron resonance experiment. These
      correlated distance constraints have been leveraged with MD simulations to learn
      about side chain packing and preferred conformers of the spin label on sites in
      an alpha-helix and a beta-strand. We found three dihedral angles of the spin
      label side chain to be most sensitive to the secondary structure where the spin
      label was located. Conformers sampled by the spin label differed between
      secondary structures as well. C(alpha)-C(alpha) distance distributions were
      constructed and used to extract details about the protein backbone mobility at
      the two spin labeled sites. These simulation studies enhance our understanding of
      the behavior of spin labels in proteins and thus expand the ability of ESR
      spectroscopy to contribute to knowledge of protein structure and dynamics.

PMID- 22404311
TI  - The analysis of 168 randomised controlled trials to test data integrity.
AB  - The purpose of this study was to use some statistical methods to assess if
      randomised controlled trials (RCTs) published by one particular author (Fujii)
      contained data of unusual consistency. I searched seven electronic databases,
      retrieving 168 RCTs published by this author between 1991 and July 2011. I
      extracted rates for categorical variables and means (SDs) for continuous
      variables, and compared these published distributions with distributions that
      would be expected by chance. The published distributions of 28/33 variables (85%)
      were inconsistent with the expected distributions, such that the likelihood of
      their occurring ranged from 1 in 25 to less than 1 in 1 000 000 000 000 000 000
      000 000 000 000 000 (1 in 10(33)), equivalent to p values of 0.04 to < 1 * 10(
      33) , respectively. In 141 human studies, 13/13 published continuous variable
      distributions were inconsistent with expected, their likelihoods being: weight <
      1 in 10(33) ; age < 1 in 10(33) ; height < 1 in 10(33) ; last menstrual period 1
      in 4.5 * 10(15) ; baseline blood pressure 1 in 4.2 * 10(5) ; gestational age 1 in
      28; operation time < 1 in 10(33) ; anaesthetic time < 1 in 10(33) ; fentanyl dose
      1 in 6.3 * 10(8) ; operative blood loss 1 in 5.6 * 10(9) ; propofol dose 1 in 7.7
      * 10(7) ; paracetamol dose 1 in 4.4 * 10(2) ; uterus extrusion time 1 in 33. The
      published distributions of 7/11 categorical variables in these 141 studies were
      inconsistent with the expected, their likelihoods being: previous postoperative
      nausea and vomiting 1 in 2.5 * 10(6) ; motion sickness 1 in 1.0 * 10(4) ; male or
      female 1 in 140; antihypertensive drug 1 in 25; postoperative headache 1 in 7.1 *
      10(10) ; postoperative dizziness 1 in 1.6 * 10(6) ; postoperative drowsiness 1 in
      3.8 * 10(4) . Distributions for individual RCTs were inconsistent with the
      expected in 96/134 human studies by Fujii et al. that reported more than two
      continuous variables, their likelihood ranging from 1 in 22 to 1 in 140 000 000
      000 (1 in 1.4 * 10(11)), compared with 12/139 RCTs by other authors. In 26 canine
      studies, the distributions of 8/9 continuous variables were inconsistent with the
      expected, their likelihoods being: right atrial pressure < 1 in 10(33) ;
      diaphragmatic stimulation (100 Hz) < 1 in 10(33) ; pulmonary artery occlusion
      pressure < 1 in 10(33) ; diaphragmatic stimulation (20 Hz) < 1 in 10(33) ; heart
      rate 1 in 6.3 * 10(10) ; mean pulmonary artery pressure 1 in 2.2 * 10(14) ; mean
      arterial pressure 1 in 6.3 * 10(7) ; cardiac output 1 in 110. Distributions were
      inconsistent with the expected in 21/24 individual canine studies that reported
      more than two continuous variables, their likelihood ranging from 1 in 345 to 1
      in 51 000 000 000 000 (1 in 5.1 * 10(13)).

PMID- 22404312
TI  - The meaning of resilience to persons living with chronic pain: an interpretive
      qualitative inquiry.
AB  - AIM: The purpose of this study was to explore the meaning of resilience, or
      adaptation in the face of adversity, to people living with chronic pain.
      BACKGROUND: Little research on the usefulness of resilience, strength-based
      approach to health care has been undertaken to date in the area of pain yet this
      approach has recently been proposed as a new model for chronic pain management.
      However, the meaning of resilience to people with chronic pain remains unknown.
      DESIGN: An interpretive qualitative design using in-depth interviews and
      phenomenological type analysis was undertaken. METHODS: Purposive sampling and in
      depth interviewing were undertaken to develop a rich description of the
      experience. RESULTS: The findings from this study revealed that while living with
      chronic pain is generally a negative experience, the participants also told
      positive stories around the following themes: (i) Recognising individual
      strength; (ii) Looking for the positives in life; (iii) Accepting the pain; and
      (iv) Learning to accept help. CONCLUSION: Chronic pain influences all aspects of
      life. Resilient individuals with chronic pain recognise the value of remaining
      positive, accepting help and learning to live with the pain. RELEVANCE TO
      CLINICAL PRACTICE: It is important for health professionals to recognise the role
      of supporting positive attributes in people living with chronic pain as a way of
      enhancing resilience.

PMID- 22404314
TI  - Short-term outcome among term singleton infants with intrapartum oligohydramnios.
AB  - AIM: To evaluate rates of early short-term neonatal complications among term
      singleton newborn infants with oligohydramnios. METHODS: Retrospective data were
      collected on 456 term infants with prenatal diagnosis of oligohydramnios and on
      matched controls, including information on maternal condition and on infant
      perinatal complications. RESULTS: Infants in the study group were born with lower
      birthweight and were SGA compared with those in the control group. Rates of renal
      malformations were significantly higher in the study group compared with the
      controls (15-3.3% and 3-0.7%, respectively; p = 0.007). Among the severe
      oligohydramnios subgroup (Amniotic Fluid Index <2), renal anomalies were even
      more prevalent compared to other infants with oligohydramnios and to the controls
      (6-9.8%, 9-2.3% and 3-0.7%, respectively; p < 0.001). The incidence of skeletal
      deformities (developmental dislocation of hip and torticollis) was higher among
      the study group. CONCLUSION: Term infants with oligohydramnios that was detected
      near birth are associated with a greater prevalence of renal malformations
      (mostly mild hydronephrosis) as well as congenital torticollis and developmental
      dislocated hips compared with controls. Postnatal renal evaluation should be
      considered in infants with severe oligohydramnios.

PMID- 22404315
TI  - Electropolymerized polythiophene photoelectrodes with density-controlled gold
      nanoparticles.
AB  - A polythiophene thin film was fabricated on gold nanoparticle (AuNP)-deposited
      indium-tin-oxide (ITO) electrodes with electropolymerization, whereas AuNPs were
      predeposited on the ITO surface. A photocurrent via photoexcited polythiophene
      increased with AuNPs which was attributed to the localized surface plasmon
      resonance. Investigation of the AuNP-density dependence on the relative
      enhancement of photocurrent revealed the maximum effect at 14% of AuNP-density,
      while 68% of AuNP-density exhibited smaller photocurrent than the polythiophene
      electrode without AuNPs. We have revealed that the effects of AuNPs saturate in
      the fairly low density region, and that the excess AuNPs even in the range of
      submonolayer resulted in the decrement of photocurrents.

PMID- 22404316
TI  - Experimental mycobacteriosis in Atlantic cod, Gadus morhua L.
AB  - Piscine mycobacteriosis causes losses in a number of fish species both in the
      wild and in aquaculture worldwide. Mycobacterium salmoniphilum infections have on
      several occasions been reported in farmed Atlantic salmon, Salmo salar L. The
      present study tested and confirmed the susceptibility of Atlantic cod, Gadus
      morhua L., an important yet relatively novel aquaculture species, to infection
      with M. salmoniphilum. Atlantic cod injected intraperitoneally with a suspension
      of this bacterium were maintained together with cohabitant (COH) fish in a flow
      through marine water system at 10-11  degrees C. The fish were supervised daily
      and samples taken at 2, 7, 14, 23, 34 and 53 weeks post-infection and examined
      pathologically, bacteriologically and using molecular biology. Injected
      mycobacteria were re-isolated in high concentrations from both injected and COH
      fish groups. Death attributable to mycobacterial infection was observed in both
      injected (47%) and COH (28%) fish groups. Extensive development of granuloma in
      visceral organs, mainly the mesenteries, spleen, kidney and liver (lesser extent)
      and at later stages of the infection in heart tissues and gills, was observed in
      both injected and COH fish. Granulomas underwent a temporal progression of
      distinct morphological stages, culminating in well-circumscribed lesions
      surrounded by normal or healing tissue. Acid-fast bacilli were detected in both
      granulomas and non-granulomatous tissues. This study confirms that Atlantic cod
      is highly susceptible to M. salmoniphilum infection and that this bacterial
      species may be a threat to cod both in the wild and in the aquaculture.

PMID- 22404318
TI  - A billiard ball in the left atrium.
AB  - An 84-year-old woman with a history of severe systolic heart failure, a
      mechanical mitral valve, and atrial fibrillation presented to the hospital with
      syncope and is found to have a free-floating intracardiac mass on transthoracic
      echocardiogram that was absent 5 months earlier. Real time three-dimensional (3D)
      transesophageal echocardiography (TEE) images reveal a billiard-ball-looking mass
      thought to be a large left atrial thrombus causing syncope by transiently
      obstructing the mitral valve orifice. Real time 3D TEE offers several potential
      advantages for the evaluation of intracardiac masses.

PMID- 22404317
TI  - A major glucuronidated metabolite of JWH-018 is a neutral antagonist at CB1
      receptors.
AB  - Recently, hydroxylated metabolites of JWH-018, a synthetic cannabinoid found in
      many K2/Spice preparations, have been shown to retain affinity and activity for
      cannabinoid type 1 receptors (CB1Rs). The activity of glucuronidated metabolites
      of JWH-018 is not known; hence, this study investigated the affinity and activity
      of a major metabolite, JWH-018-N-(5-hydroxypentyl) beta-D-glucuronide (018-gluc),
      for CB1Rs. The 018-gluc binds CB1Rs (K(i) = 922 nM), has no effect on G-protein
      activity, but antagonizes JWH-018 activity at CB1Rs. The data suggests that
      hydroxylation by cytochrome P450s and subsequent glucuronidation by UDP
      glucuronosyltransferases produces a metabolite, 018-gluc, which possesses
      antagonistic activity at CB1Rs.

PMID- 22404319
TI  - Diagnosing toxigenic Clostridium difficile: new confidence bounds show culturing
      increases sensitivity of the toxin A/B enzyme immunoassay and refute gold
      standards.
AB  - OBJECTIVE: To scrutinize published sensitivity estimates obtained using
      questionable gold standards by comparing sensitivities of culturing Clostridium
      difficile in commercially available media followed by enzyme immunoassay (EIA)
      toxin A or B detection (culture test) with applying the EIA to stool samples
      alone (direct test). METHODS: In 2008, consecutive stool samples were cultured on
      C. difficile selective culture media: (1) medium I: Clostridium difficile
      selective agar (CDSA; Becton Dickinson); (2) medium II: CLO agar (BioMerieux);
      (3) medium III: C. difficile agar according to Brazier (Oxoid). In addition, a
      direct test was performed (Ridascreen, r-Biopharm), which was also used to
      confirm toxin A or B production in the cultured C. difficile. New confidence
      bounds for sensitivities were applied, without assuming any perfect reference
      test or any conditional independence of the tests compared. RESULTS: Of 256
      liquid stool samples, 18.4% were diagnosed as positive by at least 1 of the 4
      tests; 12.8% were positive with culture medium I, 16.4% with medium II, and 13.6%
      with medium III, and 10.1% were positive by the direct test. Assuming culture
      tests to be at least as specific as the direct test yields an upper bound of 61%
      (upper 95% confidence bound (CB) 81%) for the sensitivity of the direct test.
      Assuming a prevalence of 15% yields sensitivity gains of the culture tests of at
      least 18% (lower 95% CB--4%) for medium I, 40% (lower 95% CB 21%) for medium II,
      and 23% (lower 95% CB 2%) for medium III. CONCLUSIONS: Published high
      sensitivities of direct toxin A/B EIAs, up to 96%, and the correctness of the
      cytotoxicity test assumed for their estimation are doubtful. With culture medium
      II, sensitivity gains of at least about 20% are obtainable. Direct toxin A/B EIAs
      alone are insufficiently sensitive for the clinical diagnosis of C. difficile
      infections.

PMID- 22404313
TI  - Host-pathogen checkpoints and population bottlenecks in persistent and
      intracellular uropathogenic Escherichia coli bladder infection.
AB  - Bladder infections affect millions of people yearly, and recurrent symptomatic
      infections (cystitis) are very common. The rapid increase in infections caused by
      multidrug-resistant uropathogens threatens to make recurrent cystitis an
      increasingly troubling public health concern. Uropathogenic Escherichia coli
      (UPEC) cause the vast majority of bladder infections. Upon entry into the lower
      urinary tract, UPEC face obstacles to colonization that constitute population
      bottlenecks, reducing diversity, and selecting for fit clones. A critical mucosal
      barrier to bladder infection is the epithelium (urothelium). UPEC bypass this
      barrier when they invade urothelial cells and form intracellular bacterial
      communities (IBCs), a process which requires type 1 pili. IBCs are transient in
      nature, occurring primarily during acute infection. Chronic bladder infection is
      common and can be either latent, in the form of the quiescent intracellular
      reservoir (QIR), or active, in the form of asymptomatic bacteriuria (ASB/ABU) or
      chronic cystitis. In mice, the fate of bladder infection, QIR, ASB, or chronic
      cystitis, is determined within the first 24 h of infection and constitutes a
      putative host-pathogen mucosal checkpoint that contributes to susceptibility to
      recurrent cystitis. Knowledge of these checkpoints and bottlenecks is critical
      for our understanding of bladder infection and efforts to devise novel
      therapeutic strategies.

PMID- 22404320
TI  - Genomics and the respiratory effects of air pollution exposure.
AB  - Adverse health effects from air pollutants remain important, despite improvement
      in air quality in the past few decades. The exact mechanisms of lung injury from
      exposure to air pollutants are not yet fully understood. Studying the genome
      (e.g. single-nucleotide polymorphisms (SNP) ), epigenome (e.g. methylation of
      genes), transcriptome (mRNA expression) and microRNAome (microRNA expression) has
      the potential to improve our understanding of the adverse effects of air
      pollutants. Genome-wide association studies of SNP have detected SNP associated
      with respiratory phenotypes; however, to date, only candidate gene studies of air
      pollution exposure have been performed. Changes in epigenetic processes, such DNA
      methylation that leads to gene silencing without altering the DNA sequence, occur
      with air pollutant exposure, especially global and gene-specific methylation
      changes. Respiratory cell line and animal models demonstrate distinct gene
      expression signatures in the transcriptome, arising from exposure to particulate
      matter or ozone. Particulate matter and other environmental toxins alter
      expression of microRNA, which are short non-coding RNA that regulate gene
      expression. While it is clearly important to contain rising levels of air
      pollution, strategies also need to be developed to minimize the damaging effects
      of air pollutant exposure on the lung, especially for patients with chronic lung
      disease and for people at risk of future lung disease. Careful study of genomic
      responses will improve our understanding of mechanisms of lung injury from air
      pollution and enable future clinical testing of interventions against the toxic
      effects of air pollutants.

PMID- 22404322
TI  - Caspase-1 level is higher in the scalp in androgenetic alopecia.
AB  - BACKGROUND AND OBJECTIVES: Inflammasomes that activate caspase-1 govern the
      innate immune inflammatory response. Whether hair loss associated with
      androgenetic alopecia (AGA) involves caspase-1 activation is not known. METHODS:
      Immunohistochemical staining for caspase-1 was performed on scalp tissue
      sections, and protein lysates were analyzed from individuals with AGA (no
      treatment), and individuals with AGA taking finasteride with apparent hair
      growth, individuals with AGA taking finasteride without noted hair growth, and
      normal controls. In vitro studies of human keratinocytes were conducted to
      establish effects of finasteride, dihydrotestosterone (DHT), and testosterone on
      caspase-1 levels using immunoblot analysis. RESULTS: Caspase-1 is expressed in
      normal human adult epidermal keratinocytes. Caspase-1 expression is greater in
      men with AGA. In contrast, in men taking finasteride, caspase-1 levels were lower
      and were similar to those in normal controls. In vitro studies showed that
      keratinocytes treated with finasteride in combination with testosterone or DHT
      resulted in a significant decrease in caspase-1 expression. CONCLUSION: In vivo
      and in vitro finasteride treatment resulted in lower caspase-1 expression,
      supporting the idea that androgens influence innate immunity involved in the hair
      cycle in AGA. These findings may provide a basis for development of novel
      treatments for inflammatory skin and hair diseases.

PMID- 22404321
TI  - Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that
      inhibits neuropathic pain and activity-induced spinal sensitization.
AB  - BACKGROUND AND PURPOSE: The sigma-1 (sigma(1) ) receptor is a ligand-regulated
      molecular chaperone that has been involved in pain, but there is limited
      understanding of the actions associated with its pharmacological modulation.
      Indeed, the selectivity and pharmacological properties of sigma(1) receptor
      ligands used as pharmacological tools are unclear and the demonstration that
      sigma(1) receptor antagonists have efficacy in reversing central sensitization
      related pain sensitivity is still missing. EXPERIMENTAL APPROACH: The
      pharmacological properties of a novel sigma(1) receptor antagonist (S1RA) were
      first characterized. S1RA was then used to investigate the effect of
      pharmacological antagonism of sigma(1) receptors on in vivo nociception in
      sensitizing conditions and on in vitro spinal cord sensitization in mice. Drug
      levels and autoradiographic, ex vivo binding for sigma(1) receptor occupancy were
      measured to substantiate behavioural data. KEY RESULTS: Formalin-induced
      nociception (both phases), capsaicin-induced mechanical hypersensitivity and
      sciatic nerve injury-induced mechanical and thermal hypersensitivity were dose
      dependently inhibited by systemic administration of S1RA. Occupancy of sigma(1)
      receptors in the CNS was significantly correlated with the antinociceptive
      effects. No pharmacodynamic tolerance to the antiallodynic and antihyperalgesic
      effect developed following repeated administration of S1RA to nerve-injured mice.
      As a mechanistic correlate, electrophysiological recordings demonstrated that
      pharmacological antagonism of sigma(1) receptors attenuated the wind-up responses
      in spinal cords sensitized by repetitive nociceptive stimulation. CONCLUSIONS AND
      IMPLICATIONS: These findings contribute to evidence identifying the sigma(1)
      receptor as a modulator of activity-induced spinal sensitization and pain
      hypersensitivity, and suggest sigma(1) receptor antagonists as potential novel
      treatments for neuropathic pain.

PMID- 22404323
TI  - Conformationally locked chromophores as models of excited-state proton transfer
      in fluorescent proteins.
AB  - Members of the green fluorescent protein (GFP) family form chromophores by
      modifications of three internal amino acid residues. Previously, many key
      characteristics of chromophores were studied using model compounds. However, no
      studies of intermolecular excited-state proton transfer (ESPT) with GFP-like
      synthetic chromophores have been performed because they either are nonfluorescent
      or lack an ionizable OH group. In this paper we report the synthesis and
      photochemical study of two highly fluorescent GFP chromophore analogues: p-HOBDI
      BF2 and p-HOPyDI:Zn. Among known fluorescent compounds, p-HOBDI-BF(2) is the
      closest analogue of the native GFP chromophore. These irrreversibly (p-HOBDI
      BF(2)) and reversibly (p-HOPyDI:Zn) locked compounds are the first examples of
      fully planar GFP chromophores, in which photoisomerization-induced deactivation
      is suppressed and protolytic photodissociation is observed. The photophysical
      behavior of p-HOBDI-BF2 and p-HOPyDI:Zn (excited state pK(a)'s, solvatochromism,
      kinetics, and thermodynamics of proton transfer) reveals their high photoacidity,
      which makes them good models of intermolecular ESPT in fluorescent proteins.
      Moreover, p-HOPyDI:Zn is a first example of "super" photoacidity in metal-organic
      complexes.

PMID- 22404324
TI  - Assessment of pharmacokinetic proportionality of levofloxacin and cyclosporine
      over a 100-fold dose range in healthy human volunteers.
AB  - OBJECTIVE: Levofloxacin and cyclosporine show different pharmacokinetic
      properties, but are known to be dose proportional within the therapeutic range.
      The authors evaluated the pharmacokinetic proportionality of levofloxacin and
      cyclosporine over a 100-fold dose range in healthy human volunteers, by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: Two independent,
      randomized, crossover studies were performed. For levofloxacin, eight volunteers
      were randomly assigned in a 1:1 ratio to receive a low dose (7.5 mg) orally or
      intravenously, followed by a 1-week washout period and administration via the
      alternate route. After another 1-week washout period, a therapeutic dose (750 mg)
      was administered to all eight subjects. For cyclosporine, another eight
      volunteers received a low dose (2 mg) or a therapeutic dose (200 mg) orally with
      a 1-week washout period. Drug concentrations were determined by LC-MS/MS.
      RESULTS: For levofloxacin, the mean values for dose-normalized C(max) and
      AUC(last) with the two doses were as follows: therapeutic dose, 15.2 +/- 4.6
      ng/ml/mg and 103.6 +/- 15.5 ng.h/ml/mg, respectively; low dose, 17.1 +/- 6.5
      ng/ml/mg and 72.6 +/- 8.7 ng.h/ml/mg, respectively. For cyclosporine, the mean
      values for dose-normalized C(max) and AUC(last) were as follows: therapeutic
      dose, 4.9 +/- 1.5 ng/ml/mg and 15.4 +/- 4.9 ng.h/ml/mg, respectively; low dose,
      1.6 +/- 0.6 ng/ml/mg and 9.3 +/- 7.3 ng.h/ml/mg, respectively. CONCLUSION: In
      this study levofloxacin, which is completely absorbed and primarily eliminated
      renally without modification, showed better pharmacokinetic proportionality than
      cyclosporine, which is poorly absorbed and extensively metabolized.

PMID- 22404325
TI  - Methicillin-resistant Staphylococcus aureus ST398 contamination and transmission
      in pigs after a low dose inoculation.
AB  - AIMS: Methicillin-resistant Staphylococcus aureus (MRSA) ST398 has recently been
      described as a zoonotic agent. Its transmission between animals seems to be a
      pivotal factor in its emergence and dissemination. This experimental trial was
      performed to describe MRSA ST398 contamination and transmission in pigs after a
      low dose inoculation. METHODS AND RESULTS: Twelve specific pathogen-free (SPF)
      pigs were randomly divided between two separate pens. Three pigs in each pen
      received a nasal inoculation of 2 * 10(4) colony-forming units per animal, and
      three naive pigs were left in contact with them. Every 2 days and at necropsy,
      different samples were screened for MRSA. It was detected in nasal swabs from
      five inoculated and three naive contact pigs, as early as 1 day after
      inoculation. MRSA was also found in environmental wipes but never in faecal
      samples. At necropsy, MRSA was detected in the lymph nodes of two contact pigs
      and in the tonsils and lymph nodes of three inoculated pigs. Twelve other SPF
      pigs were included as negative control in a separate room. CONCLUSION: This
      experiment showed that inoculation of a low dose of MRSA ST398 could lead to the
      horizontal transmission of the bacterium between pigs, the contamination of
      mandibular lymph nodes and the contamination of the environment without faecal
      carriage. SIGNIFICANCE AND IMPACT OF THE STUDY: The minimal inoculated dose via
      nasal route to observe transmission of MRSA ST398 between pigs is equal or lower
      to 2 * 10(4) colony-forming units per animal, and faecal excretion seems not to
      be a necessary condition for horizontal transmission.

PMID- 22404327
TI  - Penetration of ambient submicron particles into single-family residences and
      associations with building characteristics.
AB  - This work improves knowledge of particle penetration into buildings by (i)
      refining a particle penetration test method that minimizes the duration and
      invasiveness required by individual tests without sacrificing accuracy, (ii)
      applying the method in an unoccupied manufactured test house and 18 single-family
      homes in Austin, Texas, USA, and (iii) exploring correlations between particle
      penetration and building characteristics, including results from blower door air
      leakage tests. The mean (+/- s.d.) measured penetration factor of submicron
      particles (20-1000 nm, not size-resolved) was 0.47 +/- 0.15 in 19 residences that
      relied on infiltration for ventilation air, ranging from 0.17 +/- 0.03 to 0.72 +/
      0.08. Particle penetration factors (P) and outdoor particle source terms (P *
      air exchange rates) were both significantly and positively correlated with
      results from blower door air leakage tests. Outdoor particle source terms were
      also significantly and negatively correlated with the year of construction. These
      results suggest that occupants of leakier and older homes are exposed to higher
      indoor concentrations of outdoor submicron particles than those in tighter and
      newer homes, and that simple air leakage tests may be able to provide an
      approximate prediction of outdoor particle infiltration into single-family
      residences. PRACTICAL IMPLICATIONS: Results from this work suggest that knowledge
      of simple building characteristics (i.e., the year of construction and blower
      door test results) may be used to predict the ability of outdoor particles to
      infiltrate into single-family residences, which could facilitate easier estimates
      of indoor exposures to outdoor particulate matter across the building stock. The
      methods within can also be extended to other buildings and can be used to assess
      possible changes in penetration factors because of envelope retrofits. Because
      outdoor particle size distributions were not measured during this study, these
      tests should also be repeated with size-resolved particle instrumentation.

PMID- 22404326
TI  - Design, synthesis, and biological action of 20R-hydroxyvitamin D3.
AB  - The non-naturally occurring 20R epimer of 20-hydroxyvitamin D3 is synthesized
      based on chemical design and hypothesis. The 20R isomer is separated by
      semipreparative HPLC, and its structure is characterized. A comparison of 20R
      isomer to its 20S counterpart in biological evaluation demonstrates that they
      have different behaviors in antiproliferative and metabolic studies.

PMID- 22404328
TI  - Factors influencing the adherence of antipsychotic medication (Aripiprazole) in
      first-episode psychosis: findings from a grounded theory study.
AB  - Antipsychotic medication is central to the treatment of patients with first
      episode psychosis (FEP). Although non-adherence with the antipsychotic medication
      regime is a common barrier to the effective treatment of FEP, knowledge is
      limited about how patients make decisions about adhering to antipsychotic
      treatment. This qualitative study aimed to gain a greater understanding of
      patients' medication-taking practices, and their subjective experiences with
      antipsychotic treatment. In-depth, semi-structured interviews were conducted with
      patients between the ages of 18 and 35 years who were treated with Aripiprazole
      under an Early Intervention Service in the south of England. A grounded theory
      approach was used for data collection and analysis. Twelve participants were
      included in the study. The findings indicated that patients taking antipsychotic
      medication for treatment of FEP varied their medication-taking practices
      according to the effects of the illness or antipsychotic treatment on their
      lives. A conceptual model was developed and this consists of three thematic
      categories: quality of life, discernment and health status. The three main themes
      are interrelated with a cyclical outcome. The findings contribute to the
      understanding of the medication-taking practices of patients with FEP and have
      implications for prescribing practice and strategies to enhance antipsychotic
      adherence.

PMID- 22404329
TI  - Swim bladder nematodes (Anguillicoloides crassus) disturb silvering in European
      eels (Anguilla anguilla).
AB  - The introduced parasite Anguillicoloides crassus is thought to play an important
      role in the decline of freshwater eel (Anguilla spp.) populations. These
      nematodes are known to negatively affect many fitness-related traits in eels. We
      used experimental infections to study the effect of A. crassus on the relative
      size or mass of organs, and the expression of functionally relevant genes (total
      of 12 parameters) that are involved in the silvering process of Anguilla
      anguilla. Our results showed that the liver mass, the hemoglobin alpha-chain, and
      androgen receptors alpha expression levels were significantly higher in infected
      eels, whereas the freshwater rod opsin expression level and the gut mass were
      significantly lower in infected eels. Our results suggested that infected eels
      were at a more advanced stage in the silvering process than uninfected
      counterparts of similar size. These results may be explained by 2 hypotheses.
      First, A. crassus could trigger physiological mechanisms involved in the
      silvering process as a side-effect of infection. Second, eels may adjust their
      life history traits in response to infection. The implications for eel migration
      and reproductive success may be either negative or positive, depending on whether
      the response to A. crassus infection results in an additional cost of the
      parasite or is due to the phenotypic plasticity of the host.

PMID- 22404330
TI  - Sleep disturbances in critically ill patients in ICU: how much do we know?
AB  - Sleep disturbances in the intensive care unit (ICU) seem to lead to development
      of delirium, prolonged ICU stay, and increased mortality. That is why sufficient
      sleep is important for good outcome and recovery in critically ill patients. A
      variety of small studies reveal pathological sleep patterns in critically ill
      patients including abnormal circadian rhythm, high arousal and awakening index,
      reduced Slow Wave Sleep, and Rapid Eye Movement sleep. The purpose of this study
      is to summarise different aspects of sleep-awake disturbances, causes and
      handling methods in critically ill patients by reviewing the underlying
      literature. There are no studies of level 1 evidence proving the positive impact
      of the tested interventions on the critically ill patients' sleep pattern. Thus,
      disturbed sleep in critically ill patients with all the severe consequences
      remains an unresolved problem and needs further investigation.

PMID- 22404331
TI  - Follow up of the 987 blood donors found with hepatitis C virus infection over 9
      18 years.
AB  - AIM:   To follow up blood donors found with hepatitis C virus (HCV) infection, to
      improve the outcome by antiviral treatments. METHODS:   Between 1991 and 2001,
      3377 of the 1 925 860 donors (0.18%) were found to have HCV infection at the
      Hiroshima Red Cross Blood Center in Japan. Of them, 987 were able to be followed
      regularly over 9-18 years until 2009, and received antiviral treatments as
      required. RESULTS:   At the start, chronic hepatitis was diagnosed in 541
      (54.8%), cirrhosis in five (0.5%) and hepatocellular carcinoma (HCC) in one
      (0.1%), whereas the remaining 439 (44.5%) had persistently normal
      aminotransferase levels (PNAL). Hospital visits were terminated voluntarily in
      24.3% within the first year, 46.8% by 10 years and 50.9% by 17 years. Liver
      disease improved in 178 (18.0%), remained stable in 606 (61.4%) and aggravated in
      170 (17.2%). Of the 541 donors with chronic hepatitis, HCC developed in 28 (5.2%)
      and cirrhosis in 11 (2.0%), whereas HCV infection was cleared in 107 (19.8%) by
      antiviral treatments. In addition, HCV infection resolved in 54 of the 439 donors
      (12.3%) with PNAL after they had developed chronic hepatitis and received
      treatments. In donors with chronic hepatitis, the cumulative incidence of HCC was
      4.1% at 10 years. By multivariate analysis, age and diagnosis of chronic
      hepatitis at the entry were found to be independent risk factors for the
      development of HCC. CONCLUSION:   Individuals with undiagnosed HCV infection need
      to be identified and receive medical care. They have to be motivated to merit
      from this health-care program.

PMID- 22404333
TI  - Modelling the maintenance of egg polymorphism in avian brood parasites and their
      hosts.
AB  - In avian brood parasitism, egg phenotype plays a key role for both host and
      parasite reproduction. Several parrotbill species of the genus Paradoxornis are
      parasitized by the common cuckoo Cuculus canorus, and clear polymorphism in egg
      phenotype is observed. In this article, we develop a population genetics model in
      order to identify the key parameters that control the maintenance of egg
      polymorphism. The model analyses show that egg polymorphism can be maintained
      either statically as an equilibrium or dynamically with frequency oscillations
      depending on the sensitivity of the host against unlike eggs and how the parasite
      targets host nests with specific egg phenotypes. On the basis of the model, we
      discuss egg polymorphism observed in parrotbills and other host species
      parasitized by the cuckoo. We suggest the possibility that frequencies of egg
      phenotypes oscillate and we appeal for monitoring of cuckoo-host interactions
      over a large spatiotemporal scale.

PMID- 22404332
TI  - NELL1 promotes bone regeneration in polyethylene particle-induced osteolysis.
AB  - We investigated the therapeutic effects of a craniosynostosis-associated
      molecule, NEL-like molecule-1 (NELL1; NEL [a protein strongly expressed in neural
      tissue encoding the epidermal growth factor-like domain]), on osteolysis induced
      by polyethylene (PE)-particle debris. We used a murine calvarial osteolysis model
      with in vivo adenovirus (Ad)-mediated gene transfer. In total, 76 female Balb/c
      mice were randomly assigned to four groups for treatment 1 day postoperation:
      SHAM (injected with 0.1 mL saline without implantation of particles); PE control
      (injected with 0.1 mL saline after implantation of particles); PE+(Ad-GFP-NELL1)
      (injected with 0.1 mL Ad-GFP-NELL1 in saline after implantation of particles);
      and PE+(Ad-GFP) group (injected with 0.1 mL Ad-GFP in saline after implantation
      of particles). Green fluorescent protein (GFP) and NELL1 delivery in vivo after
      the injection were validated by optical imaging at 10 day postop, and then, all
      mice were sacrificed for analysis by three-dimensional (3D) microcomputed
      tomography (micro-CT), real-time polymerase chain reaction (PCR), histology, and
      biomechanical testing. Exogenous NELL1 and GFP were expressed in the osteolysis
      area for at least 9 days after the Ad-GFP-NELL1 injection. Serial 3D micro-CT
      images and testing of bone volume, bone mineral density, trabecular thickness,
      bone surface density, and connectivity density revealed that the new bone
      promoted with the Ad-GFP-NELL1 injection could almost compensate the PE-induced
      osteolysis and regenerate significantly better than with the Ad-GFP treatment.
      The expression of osteopontin (OPN) was significantly higher with Ad-GFP-NELL1
      transduction among all the samples. Real-time PCR examination confirmed the
      augmented expression of OPN, Runx-2, and receptor activator of nuclear factor
      kappa B ligand (RANKL). The elastic modulus was significantly greater with Ad-GFP
      NELL1 than with the PE and/or Ad-GFP group (p<0.01). We found no transgene
      associated toxic effects. Ad-GFP-NELL1 gene transfer effectively reversed the
      calvarial osteolysis and could be considered a new treatment for osteolysis
      through promoting bone regeneration.

PMID- 22404334
TI  - Seasonal, sex and live weight variations in feed and water consumptions of adult
      captive African Giant rats (Cricetomys gambianus, Waterhouse-1840) kept
      individually in cages.
AB  - Adult African Giant rats (Cricetomys gambianus, Waterhouse) (AGRs) (n = 231) of
      both sexes (117 bucks, 114 does) were live-trapped in the wild in Zaria, Nigeria.
      Live weight (LW), daily feed consumption (FC) and water consumption (WC) of the
      AGRs were measured during the cold-dry (CDS), hot-dry (HDS) and rainy (RS)
      seasons for 2 years with the aim of determining seasonal, sex and LW variations.
      Feed consumption was significantly different (p < 0.001) between all the seasons,
      with the lowest mean value recorded during the HDS, while the highest was
      obtained during the RS. Water consumption was also lowest (p < 0.001) during the
      HDS but did not differ significantly (p > 0.05) between the CDS and RS. Both feed
      and water consumptions were higher (p < 0.01) in the males (bucks) than the
      females (does) during the CDS and HDS, but the sex difference was not significant
      (p > 0.05) during the RS. Feed consumption correlated positively (p < 0.0001)
      with WC and relative humidity, but negatively (p < 0.0001) with LW, ambient
      temperature and heat index. In conclusion, both feed and water consumptions in
      AGRs decrease with increased seasonal heat and adult LW and are lower in does
      than in bucks during the dry seasons (CDS and HDS). Intervention may be indicated
      during the HDS to improve feed and water consumptions for optimal performance of
      the AGRs.

PMID- 22404335
TI  - Amyloid neurotoxicity is attenuated by metallothionein: dual mechanisms at work.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a
      progressive loss of memory and cognition. One of the hallmarks of AD is the
      accumulation of beta-amyloid (Abeta). Although endoplasmic reticulum stress,
      mitochondrial dysfunction, and oxidative stress have been implicated in Abeta
      toxicity, the molecular mechanism(s) of Abeta-induced neurotoxicity are not fully
      understood. In this study, we present evidence that the glia-derived stress
      protein metallothionein (MT) attenuates Abeta-induced neurotoxicity by unique
      mechanisms. MT expression was increased in brain astrocytes of a NSE-APPsw
      transgenic mouse model of AD. Astrocyte-derived MT protected N2a neuroblastoma
      cells and primary cortical neurons against Abeta toxicity with concurrent
      reduction of reactive oxygen species levels. MT reversed Abeta-induced down
      regulation of Bcl-2 and survival signaling in neuroblastoma cells. Moreover, MT
      inhibited Abeta-induced proinflammatory cytokine production from microglia. The
      neurotoxicity of Abeta-stimulated microglia was significantly attenuated by MT-I.
      The results indicate that MT released from reactive astrocytes may antagonize
      Abeta neurotoxicity by direct inhibition of Abeta neurotoxicity and indirect
      suppression of neurotoxic microglial activation. These findings broaden the
      understanding of neurotoxic mechanisms of Abeta and the crosstalk between Abeta
      and MT in AD.

PMID- 22404336
TI  - Self-aligned fabrication of graphene RF transistors with T-shaped gate.
AB  - Exceptional electronic properties of graphene make it a promising candidate as a
      material for next generation electronics; however, self-aligned fabrication of
      graphene transistors has not been fully explored. In this paper, we present a
      scalable method for fabrication of self-aligned graphene transistors by defining
      a T-shaped gate on top of graphene, followed by self-aligned source and drain
      formation by depositing Pd with the T-gate as a shadow mask. This transistor
      design provides significant advantages such as elimination of misalignment,
      reduction of access resistance by minimizing ungated graphene, and reduced gate
      charging resistance. To achieve high-yield scalable fabrication, we have combined
      the use of large-area graphene synthesis by chemical vapor deposition, wafer
      scale transfer, and e-beam lithography to deposit T-shaped top gates. The
      fabricated transistors with channel lengths in the range of 110-170 nm exhibited
      excellent performance with peak current density of 1.3 mA/MUm and peak
      transconductance of 0.5 mS/MUm, which is one of the highest transconductance
      values reported. In addition, the T-gate design enabled us to achieve graphene
      transistors with extrinsic current-gain cutoff frequency of 23 GHz and maximum
      oscillation frequency of 10 GHz. These results represent important steps toward
      self-aligned design of graphene transistors for various applications.

PMID- 22404337
TI  - Who is responsible for investigating suspected research misconduct?

PMID- 22404338
TI  - The effect of analgesic education on pain in patients undergoing breast surgery:
      within 24 hours after the operation.
AB  - AIM: The goal of this study was to assess the effect of patient information about
      the analgesics used after breast surgery, on patient's level of pain and
      mobilisation ability. BACKGROUND: Pain needs to be managed efficiently; in
      particular, for surgical cases, postoperative pain must be effectively
      controlled. Information about analgesic helped reduce the severity of pain.
      DESIGN: This study was a clinical trial comparing a test group that received
      information about the analgesic to be used and a control group that received
      information as usual. METHODS: Eighty-four patients who had a modified radical
      mastectomy or breast-conserving surgery were included in the study. Data were
      collected in a breast surgery clinic with a questionnaire, with the use of Short
      form McGill-Melzack Pain Questionnaire and the Visual Analogue Scale. The test
      group received information about the surgical pain and the analgesics that would
      be used during the postoperative period. RESULTS: The results showed that the
      level of pain reported by patients was similar in the test and control groups.
      However, the average level of postoperative pain in the test group was lower than
      that in the control group. The total pain reduction score for the test group,
      after surgery, was greater than for the control group. Following surgery, 73.8%
      of the test group and 50.0% of the control group achieved mobilisation within the
      first six hours. CONCLUSION: Informing patients about the analgesics to be used
      for their care reduced pain and provided earlier mobilisation. RELEVANCE TO
      CLINICAL PRACTICE: The findings of this study can provide guidance to nurses and
      improve analgesic control of pain management.

PMID- 22404339
TI  - Prooxidant and proinflammatory potency of air pollution particulate matter (PM2.5
      0.3) produced in rural, urban, or industrial surroundings in human bronchial
      epithelial cells (BEAS-2B).
AB  - Compelling evidence indicates that exposure to air pollution particulate matter
      (PM) affects human health. However, how PM composition interacts with PM-size to
      cause adverse health effects needs elucidation. In this study, we were also
      interested in the physicochemical characteristics and toxicological end points of
      PM2.5-0.3 samples produced in rural, urban, or industrial surroundings, thereby
      expecting to differentiate their respective in vitro adverse health effects in
      human bronchial epithelial cells (BEAS-2B). Physicochemical characteristics of
      the three PM2.5-0.3 samples, notably their inorganic and organic components, were
      closely related to their respective emission sources. Referring also to the
      dose/response relationships of the three PM2.5-0.3 samples, the most
      toxicologically relevant exposure times (i.e., 24, 48, and 72 h) and doses (i.e.,
      3.75 MUg PM/cm2 and 15 MUg PM/cm2) to use to study the underlying mechanisms of
      action involved in PM-induced lung toxicity were chosen. Organic chemicals
      adsorbed on the three PM2.5-0.3 samples (i.e., polycyclic aromatic hydrocarbons)
      were able to induce the gene expression of xenobiotic-metabolizing enzymes (i.e.,
      Cytochrome P4501A1 and 1B1, and, to a lesser extent, NADPH-quinone oxidoreductase
      1). Moreover, intracellular reactive oxygen species within BEAS-2B cells exposed
      to the three PM2.5-0.3 samples induced oxidative damage (i.e., 8-hydroxy-2'
      deoxyguanosine formation, malondialdehyde production and/or glutathione status
      alteration). There were also statistically significant increases of the gene
      expression and/or protein secretion of inflammatory mediators (i.e., notably IL-6
      and IL-8) in BEAS-2B cells after their exposure to the three PM2.5-0.3 samples.
      Taken together, the present findings indicated that oxidative damage and
      inflammatory response preceeded cytotoxicity in air pollution PM2.5-0.3-exposed
      BEAS-2B cells and supported the idea that PM-size, composition, and origin could
      interact in a complex manner to determine the in vitro responsiveness to PM.

PMID- 22404340
TI  - Replication of results of genome-wide association studies on lung cancer
      susceptibility loci in a Korean population.
AB  - BACKGROUND AND OBJECTIVE: Genome-wide association studies (GWAS) have identified
      the three chromosomal regions, 5p15, 6p21 and 15q25, as being associated with
      lung cancer risk in European populations. This study was performed to confirm
      these associations in Korean patients with lung cancer. METHODS: The genotypes at
      rs2736100, rs402710, rs401681 and rs31489 at 5p15, rs9295740 at 6p22, which is in
      extensive linkage disequilibrium with the 6p21 region, as well as rs2036534 and
      rs6495309 at 15q25, were determined in 1094 patients with lung cancer and 1100
      healthy control subjects, who were frequency matched for age and gender. RESULTS:
      The single-nucleotide polymorphisms (SNP) at 5p15 (rs2736100, adjusted odds ratio
      [aOR] 1.32, 95% confidence interval [CI] 1.03-1.67, P = 0.025; rs402710, aOR
      0.82, 95% CI 0.69-0.98, P = 0.025; rs401681, aOR 0.82, 95% CI 0.69-0.98, P =
      0.026) and at 15q25 (rs2036534, aOR 0.75, 95% CI 0.61-0.93, P = 0.01; rs6495309,
      aOR 0.81, 95% CI 0.65-1.00, P = 0.052) were significantly associated with lung
      cancer risk. The magnitude of the effect was similar to that reported in previous
      studies, and the association was in the same direction. The effect of SNP in the
      5p15 region on the risk of lung cancer was significant only for adenocarcinoma.
      The two SNP in the 15q25 region were significantly associated with lung cancer
      risk in ever-smokers and in patients with squamous-cell carcinoma. However, there
      was no association between the SNP at 6p22 and lung cancer risk. CONCLUSIONS: The
      association between SNP in the 5p15 and 15q25 regions and the risk of lung cancer
      was confirmed in a Korean population.

PMID- 22404341
TI  - Isolated noncompaction of right ventricle--a case report.
AB  - Isolated noncompaction of ventricular myocardium (INVM) is a genetic
      cardiomyopathy due to abnormal arrest in endomyocardial embryogenesis between
      fetal 5th and 8th week. Noncompaction of right ventricle alone is rare. Here we
      present one such case where a young man presented with progressive right heart
      failure and atrial fibrillation. Subsequent evaluation by echo and cardiac
      magnetic resonance imaging confirmed our diagnosis. The cardinal manifestations
      of INVM are heart failure, arrhythmia, and embolic events and our case presented
      with former two manifestations. Echocardiographic criteria for diagnosing INVM
      are discussed.

PMID- 22404343
TI  - DFT-chemical pressure analysis: visualizing the role of atomic size in shaping
      the structures of inorganic materials.
AB  - Atomic size effects have long played a role in our empirical understanding of
      inorganic crystal structures. At the level of electronic structure calculations,
      however, the contribution of atomic size remains difficult to analyze, both alone
      and relative to other influences. In this paper, we extend the concepts outlined
      in a recent communication to develop a theoretical method for revealing the
      impact of the space requirements of atoms: the density functional theory-chemical
      pressure (DFT-CP) analysis. The influence of atomic size is most pronounced when
      the optimization of bonding contacts is impeded by steric repulsion at other
      contacts, resulting in nonideal interatomic distances. Such contacts are
      associated with chemical pressures (CPs) acting upon the atoms involved. The DFT
      CP analysis allows for the calculation and interpretation of the CP distributions
      within crystal structures using DFT results. The method is demonstrated using the
      stability of the Ca(2)Ag(7) structure over the simpler CaCu(5)-type alternative
      adopted by its Sr-analogue, SrAg(5). A hypothetical CaCu(5)-type CaAg(5) phase is
      found to exhibit large negative pressures on each Ca atom, which are concentrated
      in two symmetry-related interstitial spaces on opposite sides of the Ca nucleus.
      In moving to the Ca(2)Ag(7) structure, relief comes to each Ca atom as a defect
      plane is introduced into one of these two negative-pressure regions, breaking the
      symmetry equivalence of the two sides and yielding a more compact Ca coordination
      environment. These results illustrate how the DFT-CP analysis can visually and
      intuitively portray how atomic size interacts with electronics in determining
      structure, and bridge theoretical and experimental approaches toward
      understanding the structural chemistry of inorganic materials.

PMID- 22404342
TI  - Allosteric modulation of the group III mGlu4 receptor provides functional
      neuroprotection in the 6-hydroxydopamine rat model of Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: We recently reported that broad spectrum agonist-induced
      activation of presynaptic group III metabotropic glutamate (mGlu) receptors
      within the substantia nigra pars compacta using L-2-amino-4-phosphonobutyrate
      provided functional neuroprotection in the 6-hydroxydopamine lesion rat model of
      Parkinson's disease. The aim of this study was to establish whether selective
      activation of the mGlu(4) receptor alone could afford similar functional
      neuroprotection. EXPERIMENTAL APPROACH: The neuroprotective effects of 8 days of
      supranigral treatment with a positive allosteric modulator of mGlu(4) receptors,
      (+/-)-cis-2-(3,5-dichlorphenylcarbamoyl)cyclohexanecarboxylic acid (VU0155041),
      were investigated in rats with unilateral 6-hydroxydopamine lesions. The effects
      of VU0155041 treatment on motor function were assessed using both habitual
      (cylinder test) and forced (adjusted stepping, amphetamine-induced rotations)
      behavioural tests. Nigrostriatal tract integrity was examined by analysis of
      tyrosine hydroxylase, dopa decarboxylase or dopamine levels in the striatum and
      tyrosine hydroxylase-positive cell counts in the substantia nigra pars compacta.
      KEY RESULTS: VU0155041 provided around 40% histological protection against a
      unilateral 6-hydroxydopamine lesion as well as significant preservation of motor
      function. These effects were inhibited by pre-treatment with (RS)-alpha
      cyclopropyl-4-phosphonophenylglycine, confirming a receptor-mediated response.
      Reduced levels of inflammatory markers were also evident in the brains of
      VU0155041-treated animals. CONCLUSIONS AND IMPLICATIONS: Allosteric potentiation
      of mGlu(4) receptors in the substantia nigra pars compacta provided
      neuroprotective effects in the 6-hydroxydopamine rat model A reduced inflammatory
      response may contribute, in part, to this action. In addition to the reported
      symptomatic effects, activation of mGlu(4) receptors may also offer a novel
      approach for slowing the progressive degeneration observed in Parkinson's
      disease.

PMID- 22404344
TI  - Cell permeable cocaine esterases constructed by chemical conjugation and genetic
      recombination.
AB  - Cocaine esterase (CocE) is the most efficient cocaine-metabolizing enzyme tested
      in vivo to date, displaying a rapid clearance of cocaine and a robust protection
      against cocaine's toxicity. Two potential obstacles to the clinical application
      of CocE, however, lie in its proteolytic degradation and induced immune response.
      To minimize these potential obstacles, we attempted nondisruptive cell
      encapsulation by creating a cell permeable form of CocE, which was achieved by
      covalently linking a thermally stable CocE mutant (dmCocE) with cell penetrating
      peptides (CPPs). Two types of CPPs, Tat and the low molecular weight protamine
      (LMWP), were used in this study. Two types of disulfide-bridged chemical
      conjugates, Tat-S-S-dmCocE and LMWP-S-S-dmCocE, were synthesized and then
      purified by heparin affinity chromatography. In addition, four recombinant CPP
      dmCocE fusion proteins, Tat-N-dmCocE, LMWP-N-dmCocE, dmCocE-C-Tat, and dmCocE-C
      LMWP, were constructed, expressed in Escherichia coli, and purified as soluble
      proteins. Among these six CPP-dmCocE variants, LMWP-S-S-dmCocE showed the highest
      cocaine-hydrolyzing activity, and dmCocE-C-Tat had the highest production yield.
      To evaluate their cellular uptake behavior, a covalently linked fluorophore
      (FITC) was utilized to visualize the cellular uptake of all six CPP-dmCocE
      variants in living HeLa cells. All the six variants exhibited cellular uptake,
      but their intracellular distribution phenotypes differed. While the chemical
      conjugates showed primarily cytoplasmic distribution, which was likely due to the
      reduction of the disulfide linkage between CPP and dmCocE, all the other four
      recombinant fusion proteins displayed both nuclear and cytoplasmic localization,
      with dmCocE-C-CPP exhibiting higher cytoplasmic distribution during cellular
      uptake. Based on a balanced consideration of essentials for clinical application,
      including parameters such as high cocaine-hydrolyzing efficiency, large
      production yield, major cytoplasmic distribution, etc., the dmCocE-C-Tat fusion
      protein seems to be the best candidate from this investigation. Further in vivo
      studies of the cell-encapsulated dmCocE-C-Tat in hydrolyzing cocaine and
      alleviating immunogenicity and proteolytic degradation in established, clinically
      relevant mouse models are currently underway in our laboratories. Findings from
      this research are not only useful for developing other new CPP-CocE constructs
      but also valuable for establishing a nondisruptive cell-encapsulation technology
      for other protein therapeutics that are known to be immunogenic for direct
      clinical application.

PMID- 22404345
TI  - Occurrence of moisture problems in schools in three countries from different
      climatic regions of Europe based on questionnaires and building inspections - the
      HITEA study.
AB  - The aim of this study was to assess occurrence of dampness and mold in school
      buildings in three European countries (the Netherlands, Spain, and Finland),
      representing different climatic regions. An assessment was performed utilizing
      both questionnaires and on-site building investigations, and the agreement
      between these two methods was evaluated for validation purposes. On the basis of
      questionnaire data from a representative sample of schools, different types of
      moisture problems were reported in 24-47% of all school buildings at the time of
      the study. Most commonly reported was dampness in the Netherlands, moisture/water
      damage in Spain, and mold odor in Finland. Subsequently, 20-24 schools per
      country were selected for on-site inspections by trained staff. The overall
      agreement between the questionnaire and inspection data was good (kappa-value
      0.62), however, with large differences (0.39-0.91) between countries.
      Extrapolating from the inspection data, the minimum estimates for prevalence of
      moisture problems in school buildings are 20% in the Netherlands, 41% in Spain,
      and 24% in Finland. In conclusion, moisture problems (such as moisture damage,
      dampness, and mold) are relatively common in schools. The occurrence and severity
      may vary across geographical areas, which can be partly explained by building
      characteristics. PRACTICAL IMPLICATIONS: On the basis of this study, the
      prevalence of verified moisture problems in school buildings was highest in
      Spain, but lower and similar in Finland and the Netherlands. Questionnaire-based
      surveys can be used to assess moisture problems in school buildings, but because
      of large variation in agreement with inspection data, the questionnaire needs to
      be validated by on-site inspections in a subsample of the surveyed buildings.

PMID- 22404347
TI  - Genetic polymorphisms in bovine transferrin receptor 2 (TFR2) and solute carrier
      family 40 (iron-regulated transporter), member 1 (SLC40A1) genes and their
      association with beef iron content.
AB  - Beef is considered to be an excellent source of dietary iron. However, little is
      known about the genetic control of beef iron content. We hypothesized that
      genetic polymorphisms in transferrin receptor 2 (TFR2) and solute carrier family
      40 (iron-regulated transporter), member 1 (SLC40A1) could influence skeletal
      muscle iron content. The objective of this study was to use Angus cattle to
      identify single-nucleotide polymorphisms (SNPs) in the exons and flanking regions
      of the bovine TFR2 and SLC40A1 genes and to evaluate the extent to which genetic
      variation in them was associated with bovine longissimus dorsi muscle iron
      content. Ten novel SNPs were identified in TFR2, of which one SNP tended to be
      associated (P < 0.013) with skeletal muscle iron content. Nine novel SNPs in
      SLC40A1, NC007300: rs133108154, rs137140497, rs135205621, rs136600836,
      rs134388440, rs136347850, rs134186279, rs134621419 and rs137555693, were
      identified, of which SNPs rs134388440, rs136347850 and rs137555693 were
      significantly associated (P < 0.007) with skeletal muscle iron content. High
      linkage disequilibrium was observed among SLC40A1 SNPs rs134388440, rs136347850
      and rs137555693 (R(2)  > 0.99), from which two haplotypes, TGC and CAT, were
      defined. Beef from individuals that were homozygous for the TGC haplotype had
      significantly (P < 0.001) higher iron content than did beef from CAT homozygous
      or heterozygous individuals. The estimated size of effect of the identified
      haplotypes was 0.3% of the phenotypic variance. In conclusion, our study provides
      evidence for genetic control of beef iron concentration. Moreover, SNPs
      identified in SLC40A1, rs134388440, rs136347850 and rs137555693 might be useful
      markers for the selection of Angus cattle for altered iron content.

PMID- 22404348
TI  - Association studies in QTL regions linked to bovine trypanotolerance in a West
      African crossbred population.
AB  - African animal trypanosomosis is a parasitic blood disease transmitted by tsetse
      flies and is widespread in sub-Saharan Africa. West African taurine breeds have
      the ability, known as trypanotolerance, to limit parasitaemia and anaemia and
      remain productive in enzootic areas. Several quantitative trait loci (QTL)
      underlying traits related to trypanotolerance have been identified in an
      experimentally infected F(2) population resulting from a cross between taurine
      and zebu cattle. Although this information is highly valuable, the QTL remain to
      be confirmed in populations subjected to natural conditions of infection, and the
      corresponding regions need to be refined. In our study, 360 West African cattle
      were phenotyped for the packed cell volume control under natural conditions of
      infection in south-western Burkina Faso. Phenotypes were assessed by analysing
      data from previous cattle monitored over 2 years in an area enzootic for
      trypanosomosis. We further genotyped for 64 microsatellite markers mapping within
      four previously reported QTL on BTA02, BTA04, BTA07 and BTA13. These data enabled
      us to estimate the heritability of the phenotype using the kinship matrix between
      individuals computed from genotyping data. Thus, depending on the estimators
      considered and the method used, the heritability of anaemia control ranged from
      0.09 to 0.22. Finally, an analysis of association identified an allele of the
      MNB42 marker on BTA04 as being strongly associated with anaemia control, and a
      candidate gene, INHBA, as being close to that marker.

PMID- 22404346
TI  - Design of potent and selective hybrid inhibitors of the mitotic kinase Nek2:
      structure-activity relationship, structural biology, and cellular activity.
AB  - We report herein a series of Nek2 inhibitors based on an aminopyridine scaffold.
      These compounds have been designed by combining key elements of two previously
      discovered chemical series. Structure based design led to aminopyridine (R)-21, a
      potent and selective inhibitor able to modulate Nek2 activity in cells.

PMID- 22404349
TI  - Optimal use of regression models in genome-wide association studies.
AB  - The performance of linear regression models in genome-wide association studies is
      influenced by how marker information is parameterized in the model. Considering
      the impact of parameterization is especially important when using information
      from multiple markers to test for association. Properties of the population, such
      as linkage disequilibrium (LD) and allele frequencies, will also affect the
      ability of a model to provide statistical support for an underlying quantitative
      trait locus (QTL). Thus, for a given location in the genome, the relationship
      between population properties and model parameterization is expected to influence
      the performance of the model in providing evidence for the position of a QTL. As
      LD and allele frequencies vary throughout the genome and between populations,
      understanding the relationship between these properties and model
      parameterization is of considerable importance in order to make optimal use of
      available genomic data. Here, we evaluate the performance of regression-based
      association models using genotype and haplotype information across the full
      spectrum of allele frequency and LD scenarios. Genetic marker data from 200
      broiler chickens were used to simulate genomic conditions by selecting individual
      markers to act as surrogate QTL (sQTL) and then investigating the ability of
      surrounding markers to estimate sQTL genotypes and provide statistical support
      for their location. The LD and allele frequencies of markers and sQTL are shown
      to have a strong effect on the performance of models relative to one another. Our
      results provide an indication of the best choice of model parameterization given
      certain scenarios of marker and QTL LD and allele frequencies. We demonstrate a
      clear advantage of haplotype-based models, which account for phase uncertainty
      over other models tested, particularly for QTL with low minor allele frequencies.
      We show that the greatest advantage of haplotype models over single-marker models
      occurs when LD between markers and the causal locus is low. Under these
      situations, haplotype models have a greater accuracy of predicting the location
      of the QTL than other models tested.

PMID- 22404350
TI  - Transcriptome profile analysis of porcine adipose tissue by high-throughput
      sequencing.
AB  - Novel high-throughput deep sequencing technology has dramatically changed the
      study of the functional complexity of transcriptomes. Here, we report the first
      use of this technology for analysing the wide range of transcriptional changes in
      porcine adipose tissue from different breeds and different growth phases in a
      model of obesity. Digital gene expression (DGE) data sets were instrumental to
      verifying the predicted gene models. We obtained a sequencing depth of over 3
      million tags per sample (lean, obese-a and obese-b). Tag mapping indicated
      expression of more than 76% of all genes represented in three transcript
      databases. We found the expression level of 1596 genes was significantly
      different between lean and obese-a library (P < 0.01). Among them, we found 84
      genes expressed only in the obese-a library and 95 genes expressed only in the
      lean library. Moreover, the expression of 4403 genes was found to be remarkably
      different between the obese-a and obese-b library (P < 0.01); 642 of these were
      only expressed in obese-a, and 618 were only expressed in obese-b. When mapping
      to genes, it was found that the sense transcripts account for 67.42%, 68.65% and
      66.61% of all clean tags in the lean, obese-a and obese-b libraries respectively.
      By comparison, the ratio of sense to antisense mapping of the total number of
      tags was approximately 6:1 for all libraries. This suggests that transcriptional
      regulation on the sense strand has a major role in adipose deposition, although a
      high number of antisense mapping events were also detected. We anticipated more
      than 20,000 different novel tags to be localized to the porcine genome. Among
      them, 799 different clean tags with a copy number of more than 1000 were
      detected. In conclusion, our deep sequencing analysis revealed a high degree of
      transcriptional complexity in the regulatory mechanisms of adipogenesis and
      resulted in the discovery and validation of new gene products in porcine adipose
      tissue.

PMID- 22404351
TI  - PGC-1alpha encoded by the PPARGC1A gene regulates oxidative energy metabolism in
      equine skeletal muscle during exercise.
AB  - Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha)
      has emerged as a critical control factor in skeletal muscle adaptation to
      exercise, acting via transcriptional control of genes responsible for
      angiogenesis, fatty acid oxidation, oxidative phosphorylation, mitochondrial
      biogenesis and muscle fibre type composition. In a previous study, we
      demonstrated a significant increase in mRNA expression for the gene encoding PGC
      1alpha (PPARGC1A) in Thoroughbred horse skeletal muscle following a single bout
      of endurance exercise. In this study, we investigated mRNA expression changes in
      genes encoding transcriptional coactivators of PGC-1alpha and genes that function
      upstream and downstream of PGC-1alpha in known canonical pathways. We used linear
      regression to determine the associations between PPARGC1A mRNA expression and
      expression of the selected panel of genes. Biopsy samples were obtained from the
      gluteus medius pre-exercise (T(0) ), immediately post-exercise (T(1) ) and 4 h
      post-exercise (T(2) ). Significant (P < 0.05) expression fold change differences
      relative to T(0)  were detected for genes functioning in angiogenesis (ANGP2 and
      VEGFA); Ca(2+) -dependent signalling pathway (PPP3CA); carbohydrate/glucose
      metabolism (PDK4); fatty acid metabolism/mitochondrial biogenesis (PPPARGC1B);
      haem biosynthetic process (ALAS1); insulin signalling (FOXO1, PPPARGC1A and
      SLC2A4); mitogen-activated protein kinase signalling (MAPK14 and MEF2A); and
      myogenesis (HDAC9). Gene expression associations were identified between PPARGC1A
      and genes involved in angiogenesis, mitochondrial respiration, glucose transport,
      insulin signalling and transcriptional regulation. These results suggest that PGC
      1alpha and genes regulated by PGC-1alpha play significant roles in the skeletal
      muscle response to exercise and therefore may contribute to performance potential
      in Thoroughbred horses.

PMID- 22404352
TI  - Complex traits analysis of chicken growth using targeted genetical genomics.
AB  - Dissecting the genetic control of complex trait variation remains very
      challenging, despite many advances in technology. The aim of this study was to
      use a major growth quantitative trait locus (QTL) in chickens mapped to
      chromosome 4 as a model for a targeted approach to dissect the QTL. We applied a
      variant of the genetical genomics approach to investigate genome-wide gene
      expression differences between two contrasting genotypes of a marked QTL. This
      targeted approach allows the direct quantification of the link between the
      genotypes and the genetic responses, thus narrowing the QTL-phenotype gap using
      fewer samples (i.e. microarrays) compared with the genome-wide genetical genomics
      studies. Four differentially expressed genes were localized under the region of
      the QTL. One of these genes is a potential positional candidate gene (AADAT) that
      affects lysine and tryptophan metabolism and has alternative splicing variants
      between the two genotypes. In addition, the lysine and glycolysis metabolism
      pathways were significantly enriched for differentially expressed genes across
      the genome. The targeted approach provided a complementary route to fine mapping
      of QTL by characterizing the local and the global downstream effects of the QTL
      and thus generating further hypotheses about the action of that QTL.

PMID- 22404353
TI  - A global analysis of molecular markers and phenotypic traits in local chicken
      breeds in Taiwan.
AB  - Molecular and phenotypic data have been combined to characterize the genetic
      diversity of six local chicken breeds maintained with a long-term conservation
      programme. Hua-Tung, Hsin-Yi, Ju-Chi and Quemoy originated from Taiwan, Shek-Ki
      is from South China, and Nagoya is from Japan. Molecular tools included 24
      microsatellite markers, melanocortin 1 receptor (alpha melanocyte stimulating
      hormone receptor) (MC1R), the LEI0258 marker located within the major
      histocompatibility complex (MHC), and mitochondrial DNA. Performance was recorded
      on the same individuals for body weight, panting rate in summer and antibody
      response (antigens: Newcastle disease virus and sheep red blood cells). A
      multivariate method previously proposed for taxonomy was used to combine the
      different data sets. Melanocortin 1 receptor (alpha melanocyte stimulating
      hormone receptor) and the MCW330 marker contributed the most to the first axis of
      the multiple coinertia analysis of molecular markers. Melanocortin 1 receptor
      (alpha melanocyte stimulating hormone receptor) showed evidence of selection,
      probably related to its effect on feather colour. The MHC exhibited a large
      diversity, with 16 alleles of the LEI0258 marker. Immune response traits
      contributed the most to the principal component analysis of phenotypic data.
      Eight mitochondrial DNA haplotypes related to clades A, B, C and E were
      distributed across breeds and revealed an important contribution of Indian and
      European breeds to Ju-Chi, Quemoy and Hsin-Yi. Phenotypic data contributed less
      than molecular data to the combined analysis, and two markers, LEI0258 and
      LEI0228, contributed the most. The combined analysis could clearly discriminate
      all breeds, except Ju-Chi, which was similar to Quemoy for many criteria, except
      immune response.

PMID- 22404354
TI  - Quantitative trait loci segregating in crosses between New Hampshire and White
      Leghorn chicken lines: I. egg production traits.
AB  - A genome scan was performed to detect chromosomal regions that affect egg
      production traits in reciprocal crosses between two genetically and
      phenotypically extreme chicken lines: the partially inbred line New Hampshire
      (NHI) and the inbred line White Leghorn (WL77). The NHI line had been selected
      for high growth and WL77 for low egg weight before inbreeding. The result showed
      a highly significant region on chromosome 4 with multiple QTL for egg production
      traits between 19.2 and 82.1 Mb. This QTL region explained 4.3 and 16.1% of the
      phenotypic variance for number of eggs and egg weight in the F(2)  population,
      respectively. The egg weight QTL effects are dependent on the direction of the
      cross. In addition, genome-wide suggestive QTL for egg weight were found on
      chromosomes 1, 5, and 9, and for number of eggs on chromosomes 5 and 7. A genome
      wide significant QTL affecting age at first egg was mapped on chromosome 1. The
      difference between the parental lines and the highly significant QTL effects on
      chromosome 4 will further support fine mapping and candidate gene identification
      for egg production traits in chicken.

PMID- 22404355
TI  - Systems genetics approach reveals candidate genes for parasite resistance from
      quantitative trait loci studies in agricultural species.
AB  - A systems genetics approach combining pathway analysis of quantitative trait loci
      (QTL) and gene expression information has provided strong evidence for common
      pathways associated with genetic resistance to internal parasites. Gene data,
      collected from published QTL regions in sheep, cattle, mice, rats and humans, and
      microarray data from sheep, were converted to human Entrez Gene IDs and compared
      to the KEGG pathway database. Selection of pathways from QTL data was based on a
      selection index that ensured that the selected pathways were in all species and
      the majority of the projects overall and within species. Pathways with either up-
      and down-regulated genes, primarily up-regulated genes or primarily down
      regulated genes, were selected from gene expression data. After comparing the
      data sets independently, the pathways from each data set were compared and the
      common set of pathways and genes was identified. Comparisons within data sets
      identified 21 pathways from QTL data and 66 pathways from gene expression data.
      Both selected sets were enriched with pathways involved in immune functions,
      disease and cell responses to signals. The analysis identified 14 pathways that
      were common between QTL and gene expression data, and four directly associated
      with IFNgamma or MHCII, with 31 common genes, including three MHCII genes. In
      conclusion, a systems genetics approach combining data from multiple QTL and gene
      expression projects led to the discovery of common pathways associated with
      genetic resistance to internal parasites. This systems genetics approach may
      prove significant for the discovery of candidate genes for many other
      multifactorial, economically important traits.

PMID- 22404356
TI  - A functional genomic approach to the study of the milking ability in dairy sheep.
AB  - To understand the mechanisms underlying milk ability and more precisely the
      kinetics of milk emission, we compared teat transcriptome profiles from Lacaune
      ewes in the tails of the milk flow phenotypic distribution. Two different arrays
      containing respectively 1896 and 13 168 PCR products selected from several tissue
      specific cDNA libraries, including mammary gland, allowed the identification of
      73 differentially expressed genes between teats from high and low milk flow ewes.
      Genes involved in muscle contraction were identified as over-expressed, and genes
      encoding collagen were found to be under-expressed in teats from low milk flow
      ewes. We confirmed this underexpression of COL1A1 and COL1A2 in low-milk flow
      ewes using RT-qPCR. These results suggest that milking ability may be due to the
      capacity of the teat sphincter to relax during mechanical milking. We propose
      that an optimal condition for mechanical milking may require proper relaxation of
      the teats. To our knowledge, this is the first transcriptomic analysis studying
      milking ability, using udder tissue for gene expression profiling, which
      demonstrates that mechanical milking ability is not only determined by
      morphological features but also by tissue composition.

PMID- 22404357
TI  - A molecular study of congenital erythropoietic porphyria in cattle.
AB  - Previous studies have shown that congenital erythropoietic porphyria (CEP) in
      cattle is caused by an inherited deficiency of the enzyme uroporphyrinogen III
      synthase (UROS) encoded by the UROS gene. In this study, we have established the
      pedigree of an extended Holstein family in which the disease is segregating in a
      manner consistent with autosomal recessive inheritance. Biochemical analyses
      demonstrated accumulation of uroporphyrin, thus confirming that it is indeed
      insufficient activity of UROS which is the cause of the disease. We have
      therefore sequenced all nine exons of UROS in affected and non-affected
      individuals without detecting any potential causative mutations. However, a
      single nucleotide polymorphism (SNP) located within the spliceosome attachment
      region in intron 8 of UROS is shown to segregate with the disease allele. Our
      study supports the hypothesis that CEP in cattle is caused by a mutation
      affecting UROS; however, additional functional studies are needed to identify the
      causative mutation.

PMID- 22404358
TI  - A region on BTA14 that includes the positional candidate genes LYPLA1, XKR4 and
      TMEM68 is associated with feed intake and growth phenotypes in cattle(1).
AB  - Feed cost for beef cattle is the largest expense incurred by cattle producers.
      The development of genetic markers to enhance selection of more efficient animals
      that require less feed while still achieving acceptable levels of production has
      the potential to substantially reduce production costs. A genome-wide marker
      association approach based on the Illumina BovineSNP50 BeadChipTM was used to
      identify genomic regions affecting average daily feed intake (ADFI), average
      daily gain (ADG) and residual feed intake traits in a population of 1159
      crossbred steers. This approach identified a region on BTA14 from 22.02 to 23.92
      Mb containing several single-nucleotide polymorphisms (SNPs) that have
      significant association with at least one of the traits. Two genes in this
      region, lysophospholipase 1 (LYPLA1) and transmembrane protein 68 (TMEM68),
      appeared to be logical positional and functional candidate genes. LYPLA1
      deacylates ghrelin, a hormone involved in the regulation of appetite in the rat
      stomach, while TMEM68 is expressed in bovine rumen, abomasum, intestine and
      adipose tissue in cattle, and likely affects lipid biosynthetic processes. SNPs
      lying in or near these two genes were identified by sequencing a subset of
      animals with extreme phenotypes. A total of 55 SNPs were genotyped and tested for
      association with the same population of steers. After correction for multiple
      testing, five markers within 22.79-22.84 Mb, located downstream of TMEM68, and
      between TMEM68 and the neighbouring gene XKR4, were significant for both ADFI and
      ADG. Genetic markers predictive of feed intake and weight gain phenotypes in this
      population of cattle may be useful for the identification and selection of
      animals that consume less feed, although further evaluation of these markers for
      effects on other production traits and validation in additional populations will
      be required.

PMID- 22404359
TI  - Validation and fine mapping of a QTL for ovulation rate on swine chromosome 3.
AB  - Ovulation rate (OR) is an important component of litter size, but mutation(s) in
      gene(s) underlying OR QTL have yet to be identified in pigs. Markers within an OR
      QTL on SSC3 were genotyped in three white composite lines selected for ten
      generations for increased OR or uterine capacity (UC), with one line being an
      unselected control. Numbers of corpora lutea (CL) and UC (number of fully formed
      fetuses) were collected at approximately 105 days of gestation, as well as ovary
      weight (OW), uterine length (UL) and uterine weight (UW) measurements at 160 d of
      age in generation 12 and 13 females from all three lines. Six microsatellites and
      ten single nucleotide polymorphisms (SNPs; 0-42 cM) were genotyped in pigs from
      all lines of generations 11 through 13. The allele frequencies of 24269.1,
      SW2429, 7907.2 and 7637.2 were different (P < 0.01) in the OR line compared to
      the control line. A significant (P < 0.05) association of CL with 24269.1
      (additive effect 0.65 +/- 0.32) was detected, and additive genotypic effects
      approached significance for markers at 28 through 35 cM (16963.2, 27514.1 and
      SWR1637). Haplotyping of 7637.2 and 16963.2 (31 through 32 cM) identified a
      significant additive association of haplotype 1 with CL (-0.62 +/- 0.30). These
      markers were also associated with OW (24296.1 and SWR1637), UL (16963.2, 27514.1
      and haplotypes of 7637.2/16963.2) and UW (haplotypes of 7637.2/16963.2). This
      study verifies an OR QTL on SSC3. However, based on the data, it was concluded
      that there may be two genes, at 13 through 18 cM and 28 through 35 cM,
      controlling OR on SSC3p.

PMID- 22404360
TI  - Fine mapping of porcine SSC14 QTL and SCD gene effects on fatty acid composition
      and melting point of fat in a Duroc purebred population.
AB  - The stearoyl-CoA desaturase (delta-9-desaturase; SCD) gene is a candidate gene
      for fatty acid composition. It is located on pig SSC14 in a region where
      quantitative trait loci (QTL) for fatty acid composition were previously detected
      in a Duroc purebred population. The objective of the present study was to fine
      map the QTL, to identify polymorphisms of the pig SCD gene and to examine the
      effects of SCD polymorphisms on fatty acid composition and melting point of fat
      in the population. The pigs were examined for fatty acid composition and melting
      point of inner and outer subcutaneous fat and inter- and intramuscular fat; the
      number of pigs examined was 479-521. Two SNPs (g.-353C>T and g.-233T>C) were
      identified in the promoter region of the SCD gene and were completely linked in
      the pigs from the base generation. In all pigs, 19 microsatellite markers and SCD
      haplotypes were then genotyped. Different statistical models were applied to
      evaluate the effects of QTL and the possible causality of the SCD gene variants
      with respect to the QTL. The results show that all significant QTL for C14:0,
      C18:0, C18:1 and melting point of fat were detected in the same region, located
      near the SCD gene. The results also show a significant association between SCD
      haplotypes and fatty acid composition and fat melting point in this population.
      These results indicate that the haplotype of the SCD gene has a strong effect on
      fatty acid composition and melting point of fat.

PMID- 22404361
TI  - SNP identification and polymorphism analysis in exon 2 of the horse myostatin
      gene.
AB  - The myostatin gene (MSTN) belongs to the TGF-beta superfamily of secreted growth
      and differentiation factors and is responsible for embryonic and adult skeletal
      muscle development. In this study, exon 2 of the MSTN gene, which encodes part of
      the TGF-beta pro-peptide, was sequenced in 332 horses of 20 different breeds and
      compared with the horse MSTN gene sequence deposited in GenBank. The sequences
      obtained revealed the presence of 11 haplotypes represented by 10 variable
      nucleotide mutations, eight of them corresponding to amino acid sequence changes.
      This gene shows a high variability when compared with other genes. This might be
      an indication that some breeds have the same ancestry but different pressures of
      selection.

PMID- 22404362
TI  - Significant associations of polymorphisms in the prolactin gene with growth
      traits in Asian seabass (Lates calcarifer).
AB  - Prolactin (encoded by PRL) is a multifunctional hormone involved in
      osmoregulation, reproduction, growth, development, immunomodulation, endocrine
      and metabolic regulation. We cloned the full-length cDNA of Asian seabass PRL,
      searched for polymorphism in the DNA sequence, and conducted association
      analyses. Twelve SNPs and one 4-bp deletion were identified in PRL. The SNP
      c.264+127C>G was used for linkage mapping, and this gene was mapped to linkage
      group 11. The c.264+980_983delTTGT, c.264+127C>G, c.264+138T>G, c.264+269T>C and
      c.330C>G polymorphisms were genotyped in 521 individuals with growth trait
      records. Association analyses between single markers and growth traits revealed
      that the c.264+269T>C SNP was significantly associated with body weight (BW),
      total length (TL), standard length (SL) and Fulton's condition factor (KTL and
      KSL), while the other four were not. Analysis of haplotypes showed that there
      were 10 haplotypes and 22 haplotype combinations in the population. The
      differences of BW, TL, KTL and KSL among different haplotype combinations were
      significant.

PMID- 22404363
TI  - Polymorphic but highly conserved Bogr-DRA gene in yak (Bos grunniens).

PMID- 22404364
TI  - Treatment options for Graves' orbitopathy.
AB  - INTRODUCTION: Treatment of Graves' orbitopathy (GO) is a difficult challenge and
      should be performed through a multidisciplinary approach. AREAS COVERED: This
      review covers the current treatment of hyperthyroidism and its effect on the
      course of GO. Treatment options for GO, according to its severity and activity,
      are discussed. EXPERT OPINION: In hyperthyroid patients, euthyroidism should be
      restored with antithyroid drug (ATD) therapy. High-dose i.v. glucocorticoids
      (ivGC) should be immediately given to patients with optic neuropathy, and orbital
      decompression should be performed in non-responders. Permanent treatment of
      hyperthyroidism (by radioiodine or surgery) should be planned in patients with
      moderate-to-severe and active GO, followed by a course of ivGC associated with
      orbital radiotherapy, particularly when eye muscle involvement is present.
      Patients should be carefully evaluated for liver, cardio- and cerebrovascular
      risk factors. Rehabilitative surgery (orbital decompression, squint and eyelid
      surgery) should be considered when GO is inactive, or to improve the results of
      medical therapy. In patients with mild GO long-term ATD therapy and a 6-month
      course of selenium should be used. Ablative therapy should be considered in
      patients with poorly controlled hyperthyroidism or persistently elevated thyroid
      stimulating hormone (TSH) receptor antibody levels. Oral GC should be given to
      patients with risk factors or active GO, if radioiodine is used.

PMID- 22404365
TI  - Spontaneous intracranial hypotension syndrome may mimic aseptic meningitis.
AB  - BACKGROUND: Spontaneous intracranial hypotension (SIH) is recognized with
      increasing frequency. A throbbing headache occurring or worsening in the upright
      position and improving after lying down, a so-called 'orthostatic headache', low
      cerebrospinal fluid (CSF) pressure, and diffuse pachymeningeal enhancement on
      brain magnetic resonance imaging (MRI) are the major features of the classic
      syndrome. These patients, who are admitted with fever, headache, and CSF findings
      revealing lymphocytic pleocytosis, elevated protein concentration, normal glucose
      levels, and negative culture results, are prone to be misdiagnosed with aseptic
      meningitis. The aims of this single-centre retrospective study were to determine
      the epidemiological, clinical, laboratory, and radiological features of patients
      initially evaluated as having aseptic meningitis but subsequently diagnosed with
      SIH, and to touch upon the key points of the differential diagnosis in daily
      infectious diseases practice. METHODS: Patients referred to Cerrahpasa Medical
      School with a presumed diagnosis of aseptic meningitis or viral meningitis
      between 1 January 2006 and 1 January 2011 were reviewed. Epidemiological,
      clinical, laboratory, radiological, and follow-up data obtained from the hospital
      database were processed. Patients confirmed to have SIH syndrome were included
      for evaluation. RESULTS: Eleven cases of SIH syndrome were diagnosed during the
      study period (8 male and 3 female, median age 30 y, range 21-44 y). All had
      headache, hearing changes, and nausea. Vomiting (10/11) and posterior neck pain
      (9/11) were also frequent. Seven had fever and 5 had a stiff neck. Four cases had
      lymphocytic pleocytosis, 4 cases had elevated CSF protein concentrations (> 1.5
      times the upper limit of normal), and 2 cases had slightly lower CSF glucose
      levels. Polymerase chain reaction (PCR) analyses of the CSF for Mycobacterium
      tuberculosis complex, herpes simplex viruses 1 and 2, and enteroviruses were
      negative in all cases. MRI of the 11 cases revealed signs of spontaneous CSF
      leaks with diffuse pachymeningeal gadolinium enhancement (11/11), sagging of the
      brain (9/11), enlargement of the pituitary (6/11), engorgement of the venous
      structures (5/11), and subdural fluid collections (2/11). CSF leaks were
      demonstrated by intrathecal magnetic resonance or computed tomography myelography
      at different levels along the thoracic spine (7/11), cervico-thoracic junction
      (2/11), and thoraco-lumbar junction (2/11). Autologous blood injection into the
      spinal epidural space ('blood patch') was performed for treatment. Strict bed
      rest followed, and all patients recovered fully within a week; no recurrence or
      complication was observed during the follow-up periods, which ranged from 6
      months to 5 y. CONCLUSIONS: Findings of fever, headache, and meningeal irritation
      are generally accepted as the clinical features of meningitis. When CSF findings
      are not characteristically compatible with bacterial meningitis and particularly
      when the headache is orthostatic in nature, SIH should also be included in the
      differential diagnosis. MRI findings are characteristic and clearly contribute to
      the differential diagnosis between viral meningitis and SIH.

PMID- 22404366
TI  - Surgical technique for remodelling lip deformities due to overinjection of
      silicone oil.
AB  - BACKGROUND: The injection of large volumes of silicone oil for lip augmentation
      can lead to the formation of abnormally prominent or projected lips. Conservative
      treatment measures are largely ineffective. This observational study describes
      the application of a surgical technique developed at our center for the
      correction of silicone oil-induced lip deformities. PARTICIPANTS AND METHODS:
      Fifty-nine patients presented at a tertiary medical center over a 6-year period
      with complaints of lip deformities caused by injections of silicone oil for lip
      augmentation 2 to 4 years previously. All had proven refractory to conservative
      treatment. The patients underwent individually tailored surgery consisting of a
      series of wedge-like incisions and Z-plasties to reproduce a normal lip line.
      RESULTS: Patients returned to their normal daily routine after 3 to 7 days. Only
      two patients (3.4%) required revision surgery after 6 months to correct lip
      asymmetry. Ninety percent of the patients expressed satisfaction with the
      aesthetic and functional outcome after 3 months. CONCLUSION: Our innovative,
      individually tailored surgical technique for the correction of lip deformities
      due to silicone oil injection for lip augmentation is simple and safe to perform
      and yields a satisfactory outcome in most cases.

PMID- 22404367
TI  - Plasma inflammatory mediator concentrations at ICU admission in dogs with
      naturally developing sepsis.
AB  - BACKGROUND: Identifying biomarkers to aide in the diagnosis and prognostication
      of sepsis in dogs would be valuable to veterinarians. OBJECTIVE: To compare
      plasma inflammatory mediator concentrations among dogs with sepsis, noninfectious
      systemic inflammatory response syndrome (NSIRS), and healthy dogs. ANIMALS: Dogs
      with sepsis (n = 22), NSIRS (n = 23), and healthy dogs (n = 13) presenting to the
      intensive care unit (ICU) at a veterinary teaching hospital. METHODS: Prospective
      observational study. Clinical parameters were recorded for each dog and plasma
      tumor necrosis factor (TNF) bioactivity and concentrations of interleukin (IL)-6,
      CXC chemokine ligand (CXCL)-8 and IL-10 were determined at ICU presentation.
      RESULTS: Dogs with sepsis and NSIRS were significantly more likely to have
      measurable TNF activity (sepsis 20/22; NSIRS 19/20; healthy 0/13) and IL-6
      concentration (sepsis 12/22; NSIRS 15/23; healthy 2/13), than healthy dogs.
      Healthy dogs (9/13) were significantly more likely to have measurable plasma IL
      10 concentrations than dogs with sepsis (4/19), but not NSIRS (7/20). None of the
      inflammatory mediators evaluated had optimal sensitivity or specificity for the
      diagnosis of sepsis. Twelve of 22 dogs with sepsis and 15/23 dogs with NSIRS
      survived to discharge; none of the measured biomarkers correlated with survival
      to discharge. CONCLUSIONS AND CLINICAL IMPORTANCE: Sepsis and NSIRS are
      associated with increased production of the proinflammatory cytokines TNF and IL
      6. In addition, sepsis is associated with decreased production of the anti
      inflammatory cytokine IL-10. Despite this, plasma TNF, IL-6, CXCL-8, and IL-10
      measured at ICU presentation do not appear to be valuable biomarkers to
      differentiate sepsis from NSIRS, or predict hospital outcome.

PMID- 22404368
TI  - A comprehensive mental health nursing assessment: variability of content in
      practice.
AB  - Assessment is the foundation of mental health nursing practice, but little is
      known of how it is undertaken. This paper explores how mental health nurses
      describe the content of a comprehensive mental health nursing assessment.
      Eighteen nurses who worked in inpatient and community settings either as
      clinicians or managers, ranging from new graduates to nurses with greater than 20
      years of experience, were interviewed and asked to describe the content of a
      comprehensive mental health nursing assessment. Transcribed interviews were
      analysed using a grounded theory methodology. The primary theme to emerge was one
      of variability. Most respondents hesitated and then identified different content
      areas that needed to be assessed as part of a comprehensive mental health nursing
      assessment. If the areas that are being assessed vary between nurses, then
      logically the types of interventions being offered will also vary. These results
      have implications for the education of nurses, their clinical practice, ongoing
      supervision and research into contemporary mental health nursing practice.

PMID- 22404369
TI  - A clinical assessment tool for ultrasound-guided axillary brachial plexus block.
AB  - BACKGROUND: Competency in anesthesia traditionally has been determined
      subjectively in practice. Optimal training in procedural skills requires valid
      and reliable forms of assessment. The objective was to examine a procedure
      specific clinical assessment tool for ultrasound-guided axillary brachial plexus
      block for inter-rater reliability and construct validity in a clinical setting.
      METHOD: This was a prospective observational study. Using prior work at our
      institution, the clinical assessment tool was developed consisting of a 63-point
      task-specific checklist and a global rating scale. The anesthesiologists were
      assigned to three groups based on prior experience of performing an axillary
      block: group 1 ('novices') < 10 procedures, group 2 ('intermediates') 50-80
      procedures and group 3 ('experts') > 100 procedures. Each participant performed
      two consecutive blocks that were videotaped. Two blinded independent experts
      trained in the marking of the tool evaluated the videotapes. RESULTS: There were
      five participants per group. The inter-rater reliability between assessors was
      0.842 and 0.795 for the checklist and global rating scale, respectively. There
      was a consistent difference between (each pair of) the three groups in terms of
      both the checklist and global rating scale (P < 0.05). For the checklist, expert
      vs. intermediate group P = 0.023, expert vs. novice group P < 0.001 and
      intermediate vs. novice group P = 0.019. For the global rating scale, expert vs.
      intermediate group P < 0.001, expert vs. novice group gave P < 0.001 and
      intermediate vs. novice group P = 0.023. CONCLUSION: The objective of task
      specific checklist and global rating scale are reliable and valid measures of
      axillary block performance between different levels of expertise.

PMID- 22404370
TI  - Associations between adults' recalled childhood bullying victimization, current
      social anxiety, coping, and self-blame: evidence for moderation and indirect
      effects.
AB  - Prior studies have shown that bullying victimization is common during childhood
      and may have negative effects over the short term. Evidence is also emerging that
      childhood bullying victimization in the form of teasing may precipitate social
      anxiety in adulthood. The present study extended the field by testing for
      associations between adults' recall of four common subtypes of childhood bullying
      victimization and their current social anxiety. It also provided the first test
      of whether coping moderated those associations, if they were indirect effects
      through self-blame, and if sex differences existed. Data were collected from 582
      students aged 23+ years at two universities in the UK. Collectively, and for
      social exclusion and relational victimization uniquely, the subtypes of bullying
      victimization did predict social anxiety. Evidence for hypothesized moderation
      and indirect effects was obtained but these varied by subtype of victimization
      (but not sex). The theoretical and practical implications of these results were
      discussed.

PMID- 22404371
TI  - Risk factors for mother-to-child transmission of hepatitis C virus: Maternal high
      viral load and fetal exposure in the birth canal.
AB  - AIM:   Mother-to-child transmission (MTCT) is the major transmission pathway of
      hepatitis C virus (HCV) in children. However, its risk factors remain unsettled
      for introduction of putative intervention. METHODS:   Pregnant women screened for
      HCV and MTCT in children born to antibody-positive mothers were prospectively
      studied in Tottori, Japan. RESULTS:   Among 41 856 screened women, 188 (0.45%)
      were HCV antibody-positive, of whom 61% had detectable HCV RNA. While 10 of the
      34 children (29%) born to high viral load (HVL: >=6.0 * 10(5)  IU/mL) mothers
      were infected, none born to RNA-detectable but non-HVL mothers were infected (P <
      0.001). MTCT among vaginally delivered children born to HVL mothers was analyzed.
      Children delivered after 4 h or more of labor were more frequently infected than
      were those born within 4 h of labor (P = 0.019). Premature rupture of fetal
      membranes was significantly more common in infected children than in uninfected
      children (P < 0.001). Durations of membrane rupture and labor were longer in
      infected children than in uninfected children (P = 0.008 and P = 0.040,
      respectively). Elective cesarean section that eliminates these risk factors,
      other than HVL, significantly reduced MTCT from nine of 22 (41%) to none of nine
      children (0%) (P = 0.032). CONCLUSION:   Our data suggest that contamination of
      the fetus in the birth canal with infected maternal blood is a major risk factor
      for HCV MTCT, in addition to maternal HVL. To rationalize intervention by
      elective cesarean section, the natural history of infected children should be
      carefully evaluated.

PMID- 22404372
TI  - The form of sexual selection arising from male-male competition depends on the
      presence of females in the social environment.
AB  - Sexual selection arises from social interactions, and if social environments vary
      so too should sexual selection. For example, male-male competition often occurs
      either in the presence or in the absence of females, and such changes in the
      social environment could affect the form and strength of sexual selection. Here
      we examine how the presence of a female influences selection arising from male
      male competition in a leaf-footed cactus bug, Narnia femorata, which has a
      resource defence mating system. Males compete for territories on cacti because
      females lay eggs on the cactus plants. Females are not always present when this
      competition first occurs; however, the presence or absence of the female matters.
      We found that both the form and strength of selection on male traits, those
      traits that influenced success in intrasexual competition, depended on the social
      context. When a female was not present, male size and the area of the sexually
      dimorphic hind legs was only marginally important to winning a contest. However,
      males with larger overall size and leg area were more likely to win in the
      presence of a female. There was also positive quadratic selection on these traits
      when a female was present with both the largest and the smallest males winning.
      The implication is unexpected alternative strategies when females are present.
      Our results support the notion that sexual selection should be studied under all
      relevant social contexts.

PMID- 22404374
TI  - Low-dose clarithromycin therapy modulates CD4(+)  T-cell responses in a mouse
      model of chronic Pseudomonas aeruginosa lung infection.
AB  - BACKGROUND AND OBJECTIVE: Low-dose clarithromycin (CAM) is widely used for the
      treatment of chronic respiratory infections. However, its anti-inflammatory
      mechanisms have not been fully explored. As CD4(+) T cells play an important role
      in the initiation of immune responses to infectious microorganisms, we aimed to
      investigate the effects of low-dose CAM on CD4(+) T-cell responses. METHODS:
      Fifty-four BALB/c mice were randomly divided into three groups: a control group
      (inoculated with sterile agarose beads and treated with saline from day 7), a
      saline group (inoculated with Pseudomonas aeruginosa-loaded beads and treated
      with saline from day 7) and a CAM group (identical to the saline group, except
      that saline was replaced by CAM solution). Bronchoalveolar lavage (BAL) fluid
      cell counts, bacterial load, lung tissue histology and pulmonary CD3(+) CD4(+)
      cell numbers were assessed. Levels of T helper (Th)1/Th2/Th17 cytokines and
      suppressor cytokines (interleukin (IL)-10 and transforming growth factor-beta1)
      were analysed. Messenger RNA (mRNA) levels for transcription factors for CD4(+) T
      cell subsets were determined. RESULTS: The CAM group had lower BAL fluid cell
      counts, pathological scores and pulmonary CD3(+) CD4(+) cell numbers compared
      with the saline group, whereas the bacterial load was not significantly
      different. Levels of Th1/Th17 cytokines and expression of a transcription factor
      for naturally occurring regulatory T cells (Treg) were significantly decreased in
      the CAM group compared with the saline group, whereas there was no significant
      difference in GATA-3 mRNA expression. CONCLUSIONS: This study demonstrated a
      downregulation of Th1/Th17/naturally occurring Treg responses after treatment
      with low-dose CAM in mice with chronic P. aeruginosa lung infection.

PMID- 22404373
TI  - A rapid lung de-cellularization protocol supports embryonic stem cell
      differentiation in vitro and following implantation.
AB  - Pulmonary diseases represent a large portion of neonatal and adult morbidity and
      mortality. Many of these have no cure, and new therapeutic approaches are
      desperately needed. De-cellularization of whole organs, which removes cellular
      elements but leaves intact important extracellular matrix (ECM) proteins and
      three-dimensional architecture, has recently been investigated for ex vivo
      generation of lung tissues. As specific cell culture surfaces, including ECM
      composition, profoundly affect cell differentiation, this approach offers a
      potential means of using de-cellularized lungs to direct differentiation of
      embryonic and other types of stem/progenitor cells into lung phenotypes. Several
      different methods of whole-lung de-cellularization have been reported, but the
      optimal method that will best support re-cellularization and generation of lung
      tissues from embryonic stem cells (ESCs) has not been determined. We present a 24
      h approach for de-cellularizing mouse lungs utilizing a detergent-based (Triton
      X100 and sodium deoxycholate) approach with maintenance of three-dimensional lung
      architecture and ECM protein composition. Predifferentiated murine ESCs (mESCs),
      with phenotypic characteristics of type II alveolar epithelial cells, were seeded
      into the de-cellularized lung scaffolds. Additionally, we evaluated the effect of
      coating the de-cellularized scaffold with either collagen or Matrigel to
      determine if this would enhance cell adhesion and affect mechanics of the
      scaffold. Finally, we subcutaneously implanted scaffolds in vivo after seeding
      them with mESCs that are predifferentiated to express pro-surfactant protein C
      (pro-SPC). The in vivo environment supported maintenance of the pro-SPC
      expressing phenotype and further resulted in vascularization of the implant. We
      conclude that a rapid detergent-based de-cellularization approach results in a
      scaffold that can maintain phenotypic evidence of alveolar epithelial
      differentiation of ESCs and support neovascularization after in vivo
      implantation.

PMID- 22404375
TI  - Multiplexed aptasensors and amplified DNA sensors using functionalized graphene
      oxide: application for logic gate operations.
AB  - Graphene oxide (GO) is implemented as a functional matrix for developing
      fluorescent sensors for the amplified multiplexed detection of DNA, aptamer
      substrate complexes, and for the integration of predesigned DNA constructs that
      activate logic gate operations. Fluorophore-labeled DNA strands acting as probes
      for two different DNA targets are adsorbed onto GO, leading to the quenching of
      the luminescence of the fluorophores. Desorption of the probes from the GO,
      through hybridization with the target DNAs, leads to the fluorescence of the
      respective label. By coupling exonuclease III, Exo III, to the system, the
      recycling of the target DNAs is demonstrated, and this leads to the amplified
      detection of the DNA targets (detection limit 5 * 10(-12) M). Similarly,
      adsorption of fluorophore-functionalized aptamers against thrombin or ATP onto
      the GO leads to the desorption of the aptamer-substrate complexes from GO and to
      the triggering of the luminescence corresponding to the respective fluorophore,
      thus, allowing the multiplexed analysis of the aptamer-substrate complexes. By
      designing functional fluorophore-labeled DNA constructs and their interaction
      with GO, in the presence (or absence) of nucleic acids, or two different
      substrates for aptamers, as inputs, the activation of the "OR" and "AND" logic
      gates is demonstrated.

PMID- 22404376
TI  - Secretome-derived isotope tags (SDIT) reveal adipocyte-derived apolipoprotein C-I
      as a predictive marker for cardiovascular disease.
AB  - We developed a quantitative strategy, named secretome-derived isotopic tag
      (SDIT), to concurrently identify and quantify the adipocyte-secreted plasma
      proteins from normal and high-fat-diet (HFD) induced obese mice, based on the
      application of isotope-labeled secreted proteins from cultured mouse adipocytes
      as internal standards. We detected 197 proteins with significant changes between
      normal and obese mice plasma. Importantly, a novel adipocyte-secreted plasma
      protein, apolipoprotein C-I (apoC-I), significantly increased in the obese mice
      plasma. The expression and secretion of adipocyte apoC-I was detected in
      differentiated 3T3-L1 and primary rat adipocytes. Our in vitro experiments proved
      that functional Golgi apparatus was required for apoC-I secretion. Additionally,
      obese mice had increased apoC-I production in adipose tissue. Population survey
      of 367 participants showed that the plasma level of apoC-I was significantly
      increased in obese individuals compared with healthy individuals. After multiple
      adjustments for age and sex, the odds ratios for risk factors of cardiovascular
      disease including high LDL cholesterol, hypercholesterolemia, and
      hypertriglyceridemia, respectively, were used to compare the highest with the
      lowest apoC-I quartile. Taken together, our studies provide a novel strategy to
      concurrently identify and quantify tissue-specific secreted proteins. This
      strategy can be used to identify the largest global characterization of adipocyte
      derived plasma proteome and provides a potential disease-related biomarker for
      clinical diagnoses. By selectively analyzing adipocyte-secreted proteins in
      plasma from obese vs lean murine and/or human subjects, we discovered that apoC-I
      is an adipocyte-secreted plasma protein and a predictive marker for
      cardiovascular disease.

PMID- 22404377
TI  - Lies, damn lies, and statistics.

PMID- 22404379
TI  - Don't be afraid of irrelevant words: the emotional Stroop effect is confined to
      attended words.
AB  - The emotional Stroop effect denotes slower responses to the colour of negative
      words (e.g., death) compared to neutral words (e.g., mug). Popular explanations
      assume a general power of negative words to capture visual attention. However, in
      the typical task, the irrelevant word stimulus and the relevant colour stimulus
      are perceptually integrated. We compared interference from negative words, which
      were part of the relevant visual object, to interference from negative words that
      were part of an irrelevant object, or occurred in the background, respectively.
      Results showed that only negative words in the relevant object delayed colour
      naming responses, compared to neutral words. Negative words outside the relevant
      object failed to affect performance. This finding is at odds with the claim that
      negative words could capture spatial or object-based mechanisms of visual
      attention. However, the finding is consistent with the idea that negative words
      interfere with the allocation of dimensional attention to different features of
      an attended object.

PMID- 22404378
TI  - 4-HNE adduct stability characterized by collision-induced dissociation and
      electron transfer dissociation mass spectrometry.
AB  - 4-Hydroxynonenal (4-HNE) alters numerous proteomic and genomic processes.
      Understanding chemical mechanisms of 4-HNE interactions with biomolecules and
      their respective stabilities may lead to new discoveries in biomarkers for
      numerous diseases of oxidative stress. Collision-induced dissociation (CID) and
      electron transfer dissociation (ETD) MS/MS were utilized to examine the stability
      of a 4-HNE-Cys Michael adduct. CID conditions resulted in the neutral loss of 4
      HNE, also known as a retro-Michael addition reaction (RMA). Consequently,
      performing ETD fragmentation on this same adduct did not result in RMA.
      Interestingly, 4-HNE adduct reduction via sodium borohydride (NaBH4) treatment
      stabilized against the CID induced RMA. In a direct comparison of three forms of
      4-HNE adducts, computational modeling revealed sizable shifts in the shape and
      orientation of the lowest unoccupied molecular orbital (LUMO) density around the
      4-HNE-Cys moiety. These findings demonstrate that ETD MS/MS analysis can be used
      to improve the detection of 4-HNE-protein modifications by preventing RMA
      reactions from occurring.

PMID- 22404380
TI  - The treatment of sinusitis following maxillary sinus grafting with the
      association of functional endoscopic sinus surgery (FESS) and an intra-oral
      approach.
AB  - AIM OF THE STUDY: To present the results of a prospective study on the management
      of infectious complications following maxillary sinus floor elevation procedures
      with a combined endoscopic (FESS) and intra-oral approach. MATERIALS AND METHODS:
      From 2005 to 2009, twenty consecutive patients were diagnosed for sinusal chronic
      infectious complications refractory to medical treatment following maxillary
      sinus floor elevation and grafting procedures. All patients were treated with a
      combination of functional endoscopic sinus surgery (FESS) through a transnasal
      approach and an intra-oral approach, performed by an ear, nose, and throat team
      and an oral and maxillofacial team, respectively, in the same surgical session
      under general anesthesia. RESULTS: In 16 of 20 patients, the 4-week endoscopic
      control demonstrated a complete clinical healing and recovery of the normal sinus
      ventilation and drainage. In two patients, the persisting sinusitis at the 4-week
      control was successfully treated (8th week) with an antibiotic therapy based on
      the antibiogram carried out on the bacterial culture obtained by the aspiration
      of the sinusal content. In one patient, the persisting sinusitis (3 months after
      surgery) was successfully treated with the aspiration of the infectious material
      from the maxillary sinus. In one patient, finally, it was necessary to perform a
      second combined surgical treatment to treat the persisting sinusitis. DISCUSSION
      AND CONCLUSIONS: In this study, a relevant number of cases of chronic infectious
      complications following sinus floor elevation procedures are presented. To the
      authors' knowledge, it is the first time that well-defined treatment protocols
      based on a combined endoscopic (FESS) and intra-oral surgical approach are
      proposed. The positive, albeit preliminary, results obtained in this study seem
      to validate this treatment modality.

PMID- 22404381
TI  - A RelA-dependent two-tiered regulated proteolysis cascade controls synthesis of a
      contact-dependent intercellular signal in Myxococcus xanthus.
AB  - Proteolytic cleavage of precursor proteins to generate intercellular signals is a
      common mechanism in all cells. In Myxococcus xanthus the contact-dependent
      intercellular C-signal is a 17 kDa protein (p17) generated by proteolytic
      cleavage of the 25 kDa csgA protein (p25), and is essential for starvation
      induced fruiting body formation. p25 accumulates in the outer membrane and PopC,
      the protease that cleaves p25, in the cytoplasm of vegetative cells. PopC is
      secreted in response to starvation, therefore, restricting p25 cleavage to
      starving cells. We focused on identifying proteins critical for PopC secretion in
      response to starvation. PopC secretion depends on the (p)ppGpp synthase RelA and
      the stringent response, and is regulated post-translationally. PopD, which is
      encoded in an operon with PopC, forms a soluble complex with PopC and inhibits
      PopC secretion whereas the integral membrane AAA+ protease FtsH(D) is required
      for PopC secretion. Biochemical and genetic evidence suggest that in response to
      starvation, RelA is activated and induces the degradation of PopD thereby
      releasing pre-formed PopC for secretion and that FtsH(D) is important for PopD
      degradation. Hence, regulated PopC secretion depends on regulated proteolysis.
      Accordingly, p17 synthesis depends on a proteolytic cascade including FtsH(D) 
      dependent degradation of PopD and PopC-dependent cleavage of p25.

PMID- 22404382
TI  - Docosahexaenoic acid, but not eicosapentaenoic acid, reduces the early
      inflammatory response following compression spinal cord injury in the rat.
AB  - Docosahexaenoic acid (DHA, 22 : 6) and eicosapentaenoic acid (EPA, 20 : 5) are
      omega-3 polyunsaturated fatty acids (n-3 PUFAs) with distinct anti-inflammatory
      properties. Both have neuroprotective effects acutely following spinal cord
      injury (SCI). We examined the effect of intravenous DHA and EPA on early
      inflammatory events after SCI. Saline, DHA or EPA (both 250 nmol/kg) were
      administered 30 min after T12 compression SCI, to female Sprague-Dawley rats. DHA
      significantly reduced the number of neutrophils to some areas of the injured
      epicentre at 4 h and 24 h. DHA also reduced C-reactive protein plasma levels,
      whereas EPA did not significantly reduce neutrophils or C-reactive protein.
      Laminectomy and SCI elicited a sustained inflammatory response in the liver,
      which was not reversed by the PUFAs. The chemokine KC/GRO/CINC and the cytokine
      IL-6 provide gradients for chemotaxis of neutrophils to the epicentre. At 4 h
      after injury, there was a significant increase in IL-6, KC/GRO/CINC, IL-1beta and
      tumour necrosis factor-alpha in the epicentre, with a return to baseline at 24 h.
      Neither DHA nor EPA returned their levels to control values. These results
      indicate that the acute neuroprotective effects of n-3 PUFAs in rat compression
      SCI may be only partly attributed to reduction of some of the early inflammatory
      events occurring after injury.

PMID- 22404383
TI  - Enzyme-free amplified detection of DNA by an autonomous ligation DNAzyme
      machinery.
AB  - The Zn(2+)-dependent ligation DNAzyme is implemented as a biocatalyst for the
      amplified detection of a target DNA by the autonomous replication of a nucleic
      acid reporter unit that is generated by the catalyzed ligation process. The
      reporter units enhance the formation of active DNAzyme units, thus leading to the
      isothermal autocatalytic formation of the reporter elements. The system was
      further developed and applied for the amplified detection of Tay-Sachs genetic
      disorder mutant, with a detection limit of 1.0 * 10(-11) M. Besides providing a
      versatile paradigm for the amplified detection of DNA, the system reveals a new,
      enzyme-free, isothermal, autocatalytic mechanism that introduces means for
      effective programmed synthesis.

PMID- 22404384
TI  - Citizenship, immigration, and the European social project: rights and obligations
      of individuality.
AB  - As envisioned by T.H. Marshall, social citizenship was a corrective to the
      injustices caused by the capitalist market. Entitlements and protections
      guaranteed by the welfare state would prevent social and economic exclusions that
      civil and political rights, on their own, simply could not. Such protections
      consequently would ensure social cohesion and solidarity, as well as a productive
      economy and market. European welfare states successfully followed this formula
      for the most part of the post-World War II period, however the last couple of
      decades witnessed significant changes. For one, the very meaning of 'work' and
      'worker' on which the welfare state is based has changed - flexibility, risk, and
      precariousness have become defining elements of working life. The welfare state
      itself has gone through a transformation as well, increasingly moving away from a
      system of 'passive benefits' to 'social investment' in human capital. These
      developments are coupled with an emphasis on education in 'active citizenship',
      which envisions participatory individuals who are adaptable in an increasingly
      globalized society, and ready to contribute at local, national and transnational
      levels. The emergent European social project draws on a re-alignment between
      these strands: work, social investment, and active participation. In this
      article, I consider the implications of this project for immigrant populations in
      Europe in particular and for the conceptions of citizenship and human rights in
      general. In contrast to the recent commentary on the neoliberal turn and the
      return of nation-state centered citizenship projects in Europe, I emphasize the
      broader trends in the post-World War II period that indicate a significant shift
      in the very foundations of good citizenship and social justice. The new social
      project transpires a citizenship model that privileges individuality and its
      transformative capacity as a collective good. Thus, while expanding the
      boundaries and forms of participation in society, this project at the same time
      burdens the individual, rather than the state, with the obligation of ensuring
      social cohesion and solidarity, disadvantaging not only non-European migrants but
      also the 'lesser' Europeans. The new social project brings into focus the
      relationship between universalistic individual rights and their effective
      exercise. I conclude that rather than treating human rights and citizenship as a
      dichotomy we should pay attention to their entangled practice in order to
      understand the contingent accomplishments and possible expansions of citizenship
      in Europe.

PMID- 22404385
TI  - The post-nationalization of immigrant rights: a theory in search of evidence.

PMID- 22404386
TI  - Commodifying migration: excluding migrants in Europe's emerging social model.

PMID- 22404387
TI  - Citizenship and human rights: ideals and actualities.

PMID- 22404389
TI  - Who do you think they were? How family historians make sense of social position
      and inequality in the past.
AB  - How do social comparisons over time shape perceptions of inequality? In thinking
      about subjective inequality, it is important to ask which social comparisons
      matter in establishing people's sense of relative social position and wider
      inequalities. These issues are discussed by drawing on a qualitative study of
      popular genealogy, which examines how people make sense of social position in the
      past, and explores how social change affects people's sense of social
      hierarchies. The gaze of family history promotes certain sorts of social
      comparisons, between 'then and now', and between immediate kin, which can flatten
      the sense of social hierarchies. However, the ability to determine social
      position also depends on the quality of information available, and how different
      practical engagements facilitate 'sideways' comparisons between contemporaries,
      affording different fields of vision on relative inequalities. On this evidence,
      when exploring subjective inequality it is necessary to examine when and how
      people engage in social comparison as part of everyday practical activities.

PMID- 22404390
TI  - War-making and sense-making: some technical reflections on an instance of
      'friendly fire'.
AB  - In this paper we analyse a 'friendly fire' incident from the second Gulf War and
      the controversy which came to envelop it during a coroner's inquest in 2007.
      Focusing on the cockpit video of the incident that was leaked to the media during
      that inquest, we examine what the military and civilian investigators were
      involved in reconstructing: the incident as it unfolded in real time. Our
      analysis is grounded in a praxeological perspective that draws on and links
      ethnomethodological studies of work, research into 'normal' accidents, disasters
      and risks, and recent ethnographies of the military. Based on our analysis, we
      suggest that the accounts offered after the event by the military and civilian
      inquiries should be treated less as competing descriptions than different ways of
      problematizing particular aspects of the military-political 'machineries' the
      pilots' actions were enmeshed within.

PMID- 22404391
TI  - Culture, state and varieties of capitalism: a comparative study of life insurance
      markets in Hong Kong and Taiwan.
AB  - This article examines the interplay between local culture, the state, and
      economic actors' agency in producing variation across markets. I adopt a
      political-cultural approach to examining why life insurance has been far more
      popular in Taiwan than Hong Kong, despite the presence of a cultural taboo on the
      topic of premature death in both societies. Based on interview data and
      documentary references, the findings reveal that as an independent state, the
      Taiwanese government heavily protected domestic insurance firms during their
      emergence. These domestic firms adopted a market-share approach by re-defining
      the concept of life insurance to accommodate the local cultural taboo. The
      colonial Hong Kong government, on the other hand, adopted laissez-faire policies
      that essentially favoured foreign insurance firms. When faced with the tension
      between local adaptation and the profitability of the business, these foreign
      firms chose the latter. Their reluctance to accommodate local cultures, however,
      resulted in a smaller market. I argue that state actions mediate who the dominant
      economic players are and that the nature of the dominant players affects the
      extent of localization. Specifically, the presence of competitive domestic
      players alongside transnational corporations is more likely to produce varieties
      of capitalism.

PMID- 22404392
TI  - Why different countries manage death differently: a comparative analysis of
      modern urban societies.
AB  - The sociology of death, dying and bereavement tends to take as its implicit frame
      either the nation state or a homogenous modernity. Between-nation differences in
      the management of death and dying are either ignored or untheorized. This article
      seeks to identify the factors that can explain both similarities and differences
      in the management of death between different modern western nations. Structural
      factors which affect all modern nations include urbanization and the division of
      labour leading to the dominance of professionals, migration, rationality and
      bureaucracy, information technology and the risk society. How these
      sociologically familiar structural features are responded to, however, depends on
      national histories, institutions and cultures. Historically, key transitional
      periods to modernity, different in different nations, necessitated particular
      institutional responses in the management of dying and dead bodies. Culturally,
      key factors include individualism versus collectivism, religion, secularization,
      boundary regulation, and expressivism. Global flows of death practices depend
      significantly on subjugated nations' perceptions of colonialism, neo-colonialism
      and modernity, which can lead to a dominant power's death practices being either
      imitated or rejected.

PMID- 22404393
TI  - The relationship between education and levels of trust and tolerance in Europe.
AB  - In this article we explore the relationship between education and levels of trust
      and tolerance in Europe. More specifically we assess whether the relationship
      between years of schooling and the extent to which individuals trust others in
      their communities and are tolerant towards immigrants varies across European
      countries and attempt to identify possible sources of these variations. Findings
      based on data from the first three rounds of the European Social Survey indicate
      that the association between education and levels of trust and tolerance varies
      significantly across countries and that a major source of this variation lies in
      the way in which individuals react to the level of diversity in the country where
      they live.

PMID- 22404394
TI  - Contemporary Anglo-Jewish community leadership: coping with multiculturalism.
AB  - In this article, drawing on qualitative interviews and documentary analysis, we
      argue that the Jewish community in Britain has undergone a fundamental shift
      since 1990 from a 'strategy of security', a strategy of communal leadership based
      on emphasizing the secure British citizenship and belonging of the UK's Jews, to
      a 'strategy of insecurity', where the communal leadership instead stresses an
      excess of security among Anglo-Jewry. We demonstrate this based on two case
      studies: of the Jewish renewal movement in the 1990s and the 'new antisemitism'
      phenomenon of the 2000s. We conclude that this shift is tied to the shift from a
      monocultural Britain to an officially multicultural one, and that therefore there
      are lessons that can be taken from it for the study of British and other
      multiculturalisms.

PMID- 22404395
TI  - Incremental role of three-dimensional transesophageal echocardiography in the
      assessment of mitral-aortic intervalvular fibrosa abscess.
AB  - We report a case of an elderly patient in whom live/real time three-dimensional
      transesophageal echocardiography (3DTEE) provided definitive diagnosis of mitral
      aortic intervalvular fibrosa abscess. This could not be done by two-dimensional
      transthoracic echocardiography (2DTTE) and two-dimensional transesophageal
      echocardiography (2DTEE). 3DTEE was also helpful in ruling out associated mitral
      valve endocarditis, which was initially suspected by 2DTEE leading to a mitral
      valve sparing surgery. Thus, 3DTEE provided incremental information over 2DTTE
      and 2DTEE in this patient.

PMID- 22404396
TI  - Synthesis and biological evaluation of derivatives of 2-{2-fluoro-4-[(2
      oxocyclopentyl)methyl]phenyl}propanoic acid: nonsteroidal anti-inflammatory drugs
      with low gastric ulcerogenic activity.
AB  - We previously reported that 2-fluoroloxoprofen has lower gastric ulcerogenic
      activity than loxoprofen, a nonsteroidal anti-inflammatory drug (NSAID) without
      selectivity for COX-2. We synthesized derivatives of 2-fluoroloxoprofen and
      studied their properties. Compared to 2-fluoroloxoprofen, one derivative, 11a,
      exhibited higher anti-inflammatory activity and an equivalent ulcerogenic effect.
      These results suggest that 11a could be therapeutically beneficial for use as an
      NSAID.

PMID- 22404397
TI  - Comparison of the transcriptional profiles of head and body lice.
AB  - Head and body lice are both blood-feeding parasites of humans although only the
      body louse is a potent disease vector. In spite of numerous morphological and
      life history differences, head and body lice have recently been hypothesized to
      be ecotypes of the same species. We took a comparative genomics approach to
      measure nucleotide diversity by comparing expressed sequence tag data sets from
      head and body lice. A total of 10 771 body louse and 10 770 head louse
      transcripts were predicted from a combined assembly of Roche 454 and Illumina
      sequenced cDNAs from whole body tissues collected at all life stages and during
      pesticide exposure and bacterial infection treatments. Illumina reads mapped to
      the 10 775 draft body louse gene models from the whole genome assembly predicted
      nine presence/absence differences, but PCR confirmation resulted in a single gene
      difference. Read per million base pair estimates indicated that 14 genes showed
      significant differential expression between head and body lice under our
      treatment conditions. One novel microRNA was predicted in both lice species and
      99% of the 544 transcripts from Candidatus riesia indicate that they share the
      same endosymbiont. Overall, few differences exist, which supports the hypothesis
      that these two organisms are ecotypes of the same species.

PMID- 22404398
TI  - Anatomy of the cheek: implications for soft tissue augmentation.

PMID- 22404399
TI  - Phase I study to determine the maximal tolerated dose and dose-limiting
      toxicities of orally administered idarubicin in dogs with lymphoma.
AB  - BACKGROUND: Idarubicin, a PO bioavailable anthracycline antibiotic-class
      chemotherapeutic, could have substantial convenience advantages over currently
      available similar class agents in use that require IV delivery. OBJECTIVES: The
      primary objective of this study was to determine the maximally tolerated dose
      (MTD), dose-limiting toxicities (DLTs), and basic pharmacokinetic parameters of
      oral idarubicin exposure in dogs with lymphoma after a single oral dose. A
      secondary objective was to document preliminary antitumor efficacy in an expanded
      treatment cohort using the established MTD. ANIMALS: Client-owned dogs with
      measurable lymphoma. METHODS: Dogs (n = 31) were enrolled in a prospective open
      label phase I study of oral idarubicin. By means of a 3 + 3 cohort design, dose
      escalations were made with 3 dogs per dose level, and the MTD was established
      based on the number of patients experiencing a DLT. Plasma concentrations of
      idarubicin and idarubicinol were determined by postdose sampling. Assessment of
      antitumor efficacy focused on evaluation of accessible, measurable lymph nodes
      and skin lesions by modified RECIST guidelines. RESULTS: The MTD in dogs > 15 kg
      body weight was 22 mg/m(2) . Adverse hematologic events (neutropenia and
      thrombocytopenia) were the predominant DLT and generally correlated with higher
      plasma concentrations of idarubicin and idarubicinol. CONCLUSIONS AND CLINICAL
      IMPORTANCE: PO administered idarubicin was generally well-tolerated and had
      preliminary antitumor activity in dogs with lymphoma. Furthermore, the potential
      clinical advantage of a safe and efficacious oral anthracycline alternative
      supports further investigations of this agent in repeated-dose, randomized
      clinical trials.

PMID- 22404400
TI  - Commentary: coeliac disease, mortality and malignancy.

PMID- 22404402
TI  - Commentary: HBsAg levels as predictor of sustained response to peg interferon in
      HBeAg-negative chronic hepatitis B.

PMID- 22404404
TI  - Commentary: effect of pregabalin on acid-induced oesophageal hypersensitivity.

PMID- 22404405
TI  - Commentary: ursodeoxycholic acid as chemoprevention in inflammatory bowel disease
      and primary sclerosing cholangitis.

PMID- 22404407
TI  - Commentary: BMI and the need for adalimumab dose escalation in Crohn's disease.

PMID- 22404408
TI  - Commentary: short-term stability of subtypes in the irritable bowel syndrome.

PMID- 22404411
TI  - Letter: the ethics of using inferior regimens in H. pylori randomised trials.

PMID- 22404412
TI  - Letter: the ethics of using inferior regimens in H. pylori randomised trials -
      invited comment.

PMID- 22404413
TI  - Letter: the ethics of using inferior regimens in H. pylori randomised trials -
      invited comment.

PMID- 22404415
TI  - Letter: identication of probiotics by specific strain name.

PMID- 22404417
TI  - Letter: liver dysfunction and survival in hepatocellular carcinoma treated by
      transarterial chemoembolisation.

PMID- 22404419
TI  - Optical and spin coherence properties of nitrogen-vacancy centers placed in a 100
      nm thick isotopically purified diamond layer.
AB  - We have studied optical and spin properties of near-surface nitrogen-vacancy (NV)
      centers incorporated during chemical vapor phase growth of isotopically purified
      (12)C single-crystal diamond layers. The spectral diffusion-limited line width of
      zero-phonon luminescence from the NV centers is 1.2 +/- 0.5 GHz, a considerable
      improvement over that of NV centers formed by ion implantation and annealing.
      Enhanced spin dephasing times (T(2)* ~ 90 MUs, T(2) ~ 1.7 ms) due to the
      reduction of (13)C nuclear spins persist even for NV centers placed within 100 nm
      of the surface.

PMID- 22404421
TI  - Fenofibric acid for hyperlipidemia.
AB  - INTRODUCTION: 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
      inhibitors (i.e., statins) are the mainstay of therapy for hyperlipidemia, as per
      the current National Cholesterol Education Program (NCEP) recommendation.
      However, the role of other agents, such as the fibrates, is continually being
      debated in the context of incremental risk reduction, especially in the setting
      of mixed dyslipidemia. Results from the ACCORD Trial have further added to the
      confusion. Fibrates also have a role to play in familial hyperlipidemias and in
      hypertriglyceridemia. Fenofibric acid is one of the newly approved forms of
      fenofibrate with enhanced bioavailability and was recently approved by the Food
      and Drug Administation (FDA) for the treatment of various types of
      hyperlipidemia, in conjunction with statins. AREAS COVERED: This article reviews
      the role of fenofibric acid in the context of results from recent randomized
      trials on fenofibrate, including the ACCORD Trial. It discusses the current
      status of fenofibric acid in the management of dyslipidemia, especially in
      combination with statins, and also addresses the comparative efficacy and safety
      profile of this new molecule against other agents in its class. EXPERT OPINION:
      Fenofibric acid in combination with low- to moderate-dose statins is an effective
      and safe option in the treatment of mixed dyslipidemia, although the long-term
      effects on cardiovascular risk reduction need to be explored further.

PMID- 22404422
TI  - Community-associated methicillin-resistant Staphylococcus aureus endocarditis
      'down under': case series and literature review.
AB  - Infective endocarditis is a common complication of Staphylococcus aureus
      bacteraemia, but literature reports of community-associated methicillin-resistant
      S. aureus (CA-MRSA) endocarditis are relatively uncommon and mostly comprise
      intravenous drug users (IVDUs) with the USA300 strain. We report 5 cases of CA
      MRSA endocarditis in previously healthy young Australian adults, 4 in IVDUs.
      Morbidity was high with frequent septic emboli; 3 patients required cardiac
      surgery and 1 patient died. Typing revealed the 2 most common Australian strains,
      the Panton-Valentine leukocidin (PVL)-positive ST93 (Queensland) strain and the
      PVL-negative ST1 (WA-MRSA-1) strain.

PMID- 22404424
TI  - In situ supramolecular assembly and modular modification of hyaluronic acid
      hydrogels for 3D cellular engineering.
AB  - A facile in situ supramolecular assembly and modular modification of
      biocompatible hydrogels were demonstrated using cucurbit[6]uril-conjugated
      hyaluronic acid (CB[6]-HA), diaminohexane-conjugated HA (DAH-HA), and tags-CB[6]
      for cellular engineering applications. The strong and selective host-guest
      interaction between CB[6] and DAH made possible the supramolecular assembly of
      CB[6]/DAH-HA hydrogels in the presence of cells. Then, the 3D environment of
      CB[6]/DAH-HA hydrogels was modularly modified by the simple treatment with
      various multifunctional tags-CB[6]. Furthermore, we could confirm in situ
      formation of CB[6]/DAH-HA hydrogels under the skin of nude mice by sequential
      subcutaneous injections of CB[6]-HA and DAH-HA solutions. The fluorescence of
      modularly modified fluorescein isothiocyanate (FITC)-CB[6] in the hydrogels was
      maintained for up to 11 days, reflecting the feasibility to deliver the proper
      cues for cellular proliferation and differentiation in the body. Taken together,
      CB[6]/DAH-HA hydrogels might be successfully exploited as a 3D artificial
      extracellular matrix for various tissue engineering applications.

PMID- 22404423
TI  - Matched sibling donor stem cell transplantation for Fanconi anemia patients with
      T-cell somatic mosaicism.
AB  - SCT from HLA-identical sibling donors is generally associated with an excellent
      survival in FA patients if performed prior to the development of MDS or leukemia.
      However, the optimal conditioning regimen has not been defined. We report here
      our experience with 15 Japanese FA patients who underwent HLA-matched sibling
      donor SCT. The aim of this study is to compare radiation-based conditioning to
      Flu-based conditioning for FA patients in a Japanese population where the T-cell
      somatic mosaicism is higher than in the Caucasian population. Eight patients (a
      group) received a radiation-based conditioning (500-600 cGy of
      thoracoabdominal/TBI) with CY dose modification (20-120 mg/kg), and ATG; two
      patients exhibited rejection. Seven patients (b-group) received CY (40 mg/kg),
      150-180 mg/m(2) of Flu, and ATG. Durable engraftment was demonstrated in all
      patients. In FA patients, Flu-based conditioning may allow stable engraftment in
      matched sibling donor transplantation without radiation, even in patients with T
      cell somatic mosaicism.

PMID- 22404425
TI  - The influence of indirect and direct emotional processing on memory for facial
      expressions.
AB  - We used the remember-know procedure (Tulving, 1985 ) to test the behavioural
      expression of memory following indirect and direct forms of emotional processing
      at encoding. Participants (N=32) viewed a series of facial expressions (happy,
      fearful, angry, and neutral) while performing tasks involving either indirect
      (gender discrimination) or direct (emotion discrimination) emotion processing.
      After a delay, participants completed a surprise recognition memory test. Our
      results revealed that indirect encoding of emotion produced enhanced memory for
      fearful faces whereas direct encoding of emotion produced enhanced memory for
      angry faces. In contrast, happy faces were better remembered than neutral faces
      after both indirect and direct encoding tasks. These findings suggest that
      fearful and angry faces benefit from a recollective advantage when they are
      encoded in a way that is consistent with the predictive nature of their threat.
      We propose that the broad memory advantage for happy faces may reflect a form of
      cognitive flexibility that is specific to positive emotions.

PMID- 22404426
TI  - Clinical significance of hyperbilirubinemia among HIV-1-infected patients treated
      with atazanavir/ritonavir through 96 weeks in the CASTLE study.
AB  - CASTLE was a randomized 96-week study that demonstrated that atazanavir/ritonavir
      (ATV/r) was noninferior to lopinavir/ritonavir (LPV/r) in treatment-naive HIV
      infected patients. Analyses were carried out among patients who received ATV/r in
      the CASTLE study to better understand the clinical significance of unconjugated
      hyperbilirubinemia associated with administration of boosted ATV.
      Hyperbilirubinemia was defined as total bilirubin (conjugated and unconjugated)
      elevation greater than 2.5 times the upper limit of normal (grade 3-4). Patients
      in the ATV/r arm were assessed based on the presence or absence of
      hyperbilirubinemia through week 96. Analyses included number of confirmed
      virologic responders (CVR; HIV RNA<50 copies per milliliter), impact of
      hyperbilirubinemia on symptoms, elevations in liver enzymes, patient quality of
      life, and medication adherence. Through 96 weeks in the CASTLE study, 44% of
      patients who received ATV/r had hyperbilirubinemia at any time point, and between
      12.5% and 21.6% had hyperbilirubinemia at any single study visit. At 96 weeks,
      74% of patients overall and 84% and 69% of patients with and without
      hyperbilirubinemia, respectively, achieved CVR. Symptoms of jaundice or scleral
      icterus occurred in 5% of patients overall and in 11% with hyperbilirubinemia and
      0% without hyperbilirubinemia. Four percent of patients with and 3% of patients
      without hyperbilirubinemia had grade 3-4 elevations in liver transaminases. Less
      than 1% of patients discontinued treatment due to hyperbilirubinemia. There were
      no differences in quality of life or adherence between patients with or without
      hyperbilirubinemia. In the CASTLE study, hyperbilirubinemia observed in the ATV/r
      group did not negatively impact clinical outcomes in HIV-infected patients.

PMID- 22404427
TI  - HIV risk perception and preexposure prophylaxis interest among a heterosexual
      population visiting a sexually transmitted infection clinic.
AB  - Low perception of HIV risk despite behaviors associated with increased risk is
      thought to be a contributing factor for a higher prevalence of HIV in blacks than
      other groups in the United States. We sought to determine HIV risk perception and
      its impact on safer sex practices and interest in preexposure prophylaxis (PrEP).
      From August 1 to October 31, 2010, an anonymous survey was conducted at a
      sexually transmitted infection clinic asking questions about demographics, risk
      behaviors, and PrEP interest. Participants were categorized into high-risk,
      moderate-risk, and low-risk groups according to predefined HIV risk
      characteristics. Only heterosexual high-risk participants were further assessed
      for their risk perception, condom use and PrEP interest. There were 494
      participants; 63% male, 70% blacks, 88% heterosexual; 83% were categorized into
      the high-risk group. Of the 359 heterosexual high-risk participants, 301 (84%)
      perceived themselves at no or low-risk. Rates of consistent condom use with
      vaginal, oral, and anal sex were low (<20%) in this group despite high levels of
      knowledge about HIV transmission risks. Rates of condom use were not affected by
      risk perception. No interest in PrEP was associated with low education level
      (adjusted odds ratio 4.97; p=0.02) and low risk perception. These findings
      suggest that despite having knowledge about HIV transmission risks, the majority
      of high-risk participants did not recognize their risks and used condoms with low
      frequency. Low risk perception and low education level may impact PrEP interest.
      Enhanced interventions are needed to improve HIV risk perception, safer sex
      practices, and knowledge about PrEP.

PMID- 22404428
TI  - Correlation between circulating fibrocytes, and activity and progression of
      interstitial lung diseases.
AB  - BACKGROUND AND OBJECTIVE: Interstitial lung diseases (ILD) are characterized by
      progressive interstitial pulmonary fibrosis and a decline in lung function.
      Fibrocytes are bone marrow-derived mesenchymal progenitor cells that may play a
      role in the pathogenesis of pulmonary fibrosis. Circulating fibrocyte numbers
      have been correlated with the prognosis of patients with idiopathic pulmonary
      fibrosis. The aim of the present study was to evaluate the relationship between
      circulating fibrocytes, and parameters of disease activity and progression in
      several groups of patients with ILD. METHODS: The study population comprised 41
      patients with ILD and seven healthy control subjects. Circulating CD45(+)
      collagen-I(+) fibrocytes were evaluated by flow cytometry. RESULTS: The number of
      circulating fibrocytes was significantly increased in all patients with ILD and
      particularly in patients with idiopathic interstitial pneumonitis and
      interstitial pneumonitis associated with collagen vascular disease as compared
      with healthy control subjects. The numbers of circulating fibrocytes were
      significantly correlated with pulmonary function test parameters and with serum
      levels of sialylated carbohydrate antigen, a marker of disease activity. Temporal
      changes in circulating fibrocyte numbers were evaluated in two patients, and the
      results suggested that these changes correlated with the activity of ILD.
      CONCLUSIONS: The results from this study provide further evidence for the role of
      circulating fibrocytes in fibrotic lung diseases.

PMID- 22404429
TI  - Nesca, a novel neuronal adapter protein, links the molecular motor kinesin with
      the pre-synaptic membrane protein, syntaxin-1, in hippocampal neurons.
AB  - Vesicular transport in neurons plays a vital role in neuronal function and
      survival. Nesca is a novel protein that we previously identified and herein
      describe its pattern of expression, subcellular localization and protein-protein
      interactions both in vitro and in vivo. Specifically, a large proportion of Nesca
      is in tight association with both actin and microtubule cytoskeletal proteins.
      Nesca binds to F-actin, microtubules, betaIII and acetylated alpha-tubulin, but
      not neurofilaments or the actin-binding protein drebrin, in in vitro-binding
      assays. Nesca co-immunoprecipitates with kinesin heavy chain (KIF5B) and kinesin
      light-chain motors as well as with the synaptic membrane precursor protein,
      syntaxin-1, and is a constituent of the post-synaptic density. Moreover, in vitro
      binding assays indicate that Nesca directly binds KIF5B, kinesin light-chain and
      syntaxin-1. In contrast, Nesca does not co-immunoprecipitate with the kinesin
      motors KIF1B, KIF3A nor does it bind syntaxin-4 or the synaptosome-associated
      protein 25 kDa (SNAP-25) in vitro. Nesca expression in neurons is highly
      punctuate, co-stains with syntaxin-1, and is found in fractions containing
      markers of early endosomes and Golgi suggesting that it is involved in vesicular
      transport. Collectively, these data suggest that Nesca functions as an adapter
      involved in neuronal vesicular transport including vesicles containing soluble N
      ethylmaleimide sensitive factor attachment protein receptors that are essential
      to exocytosis.

PMID- 22404430
TI  - We cannot take oranges for apples in the field of platelet-rich plasma products.

PMID- 22404431
TI  - Caffeine ingestion and antigen-stimulated human lymphocyte activation after
      prolonged cycling.
AB  - This study investigated the effect of caffeine ingestion on antigen-stimulated T-
      (CD4(+) and CD8(+) ) and natural killer (NK)- (CD3(-) CD56(+) ) cell activation
      after prolonged, strenuous cycling. In a randomized cross-over design, nine male
      endurance cyclists (age: 22 +/- 3 years, VO(2peak) : 62 +/- 4 mL/kg/min, mean +/-
      SD) cycled for 90 min at 70% VO(2peak) 60 min after ingesting 6 mg/kg body mass
      of caffeine (CAF) or placebo (PLA). Venous blood samples were obtained before
      supplementation, pre-exercise, immediately post-exercise and 1 h post-exercise.
      Whole blood was stimulated with Pediacel (five in one) vaccine. At 1 h post
      exercise the number of antigen-stimulated CD4(+) cells expressing CD69 decreased
      on CAF compared with PLA [15 (17) * 10(6) vs 23 (22) * 10(6) cells/L, P<0.05]. In
      addition, the geometric mean fluorescence intensity (GMFI) of CD69 expression on
      antigen-stimulated CD8(+) cells decreased on CAF compared with PLA 1 h post
      exercise [78 (10)% vs 102 (24)%, P<0.05]. At the same time-point GMFI of CD69
      expression on antigen-stimulated CD3(-) CD56(+) cells was increased on CAF
      compared with PLA [103 (9)% vs 87 (8)%, P<0.05]. These findings suggest that
      caffeine reduces antigen-stimulated CD69 expression on T cells while at the same
      time increases NK-cell activation 1 h after intensive cycling.

PMID- 22404432
TI  - Low prevalence of the somatic M918T RET mutation in micro-medullary thyroid
      cancer.
AB  - BACKGROUND: The prevalence of RET somatic mutations in sporadic medullary thyroid
      cancer (MTCs) is ~40%-50%, and the most frequent somatic mutation is M918T. RET
      positive MTCs have been demonstrated to have a more advanced stage at diagnosis
      and a worse outcome. AIMS: The aim of the present work was to compare the
      prevalence of RET somatic mutations in sporadic microMTCs (<1 cm) and in larger
      MTCs. PATIENTS: We analyzed the M918T RET point mutation in 160 sporadic MTC
      cases. Tumors were classified according to their size: group A, <1 cm; group B,
      >1 and <2 cm; group C, >2 and <3 cm; and group D, >3 cm. RESULTS: The overall
      prevalence of the somatic M918T RET mutation was 19.4% (31/160). RET mutations
      were distributed differently among the four groups. The prevalence was 11.3%
      (6/53) in group A, 11.8% (8/68) in group B, 31.8% (7/22) in group C, and 58.8%
      (10/17) in group D, exhibiting an increase with increasing size of the tumor.
      When comparing the prevalence of mutations in the four groups, we found a lower
      prevalence in microMTCs (p<0.0001). CONCLUSIONS: The overall prevalence of RET
      somatic mutations was lower than expected, and the prevalence of the somatic
      M918T RET mutation was significantly lower in microMTCs than in larger tumors. To
      explain this finding, we can hypothesize either that other oncogene(s) might be
      responsible for the majority of microMTC, thus identifying a tumor subset, or
      that the RET mutation might, or might not, occur later during tumor progression.

PMID- 22404433
TI  - Whole-genome sequencing and the physician.

PMID- 22404434
TI  - Artificial selection on allometry: change in elevation but not slope.
AB  - To what extent within-species (static) allometries constitute a constraint on
      evolution is the subject of a long-standing debate in evolutionary biology. A
      prerequisite for the constraint hypothesis is that static allometries are hard to
      change. Several studies have attempted to test this hypothesis with artificial
      selection experiments, but their results remain inconclusive due to various
      methodological issues. Here, we present results from an experiment in which we
      selected independently on the slope and the elevation of the allometric
      relationship between caudal-fin size and body size in male guppies (Poecilia
      reticulata). After three episodes of selection, the allometric elevation (i.e.
      intercept at constant slope) had diverged markedly between the lines selected to
      increase or decrease it, and showed a realized heritability of 50%. In contrast,
      the allometric slope remained unaffected by selection. These results suggest that
      the allometric elevation is more evolvable than the allometric slope, this latter
      representing a potential constraint on adaptive trait evolution. To our
      knowledge, this study is the first artificial-selection experiment that directly
      tests the evolvability of static allometric slopes.

PMID- 22404435
TI  - Retrospective evaluation of bleeding tendency and simultaneous thrombin and
      plasmin generation in patients with rare bleeding disorders.
AB  - Rare bleeding disorders (RBDs) are a heterogeneous group of diseases with varying
      bleeding tendency, only partially explained by their laboratory phenotype. We
      analysed the separate groups of RBD abnormalities, and we investigated
      retrospectively whether the novel haemostasis assay (NHA) was able to
      differentiate between bleeding tendency. We have performed simultaneous thrombin
      generation (TG) and plasmin generation (PG) measurements in 41 patients affected
      with deficiencies in prothrombin, factor (F) V, FVII, FX, FXIII and fibrinogen.
      Parameters of the NHA were classified based on (major or minor) bleeding
      tendency. Patients with deficiencies in coagulation propagation (FII, FV and FX)
      and major type of bleedings had diminished TG (expressed as AUC) below 20% of
      control. FVII deficient patients only had prolonged thrombin lag-time ratio of
      1.6 +/- 0.2 (P < 0.05) and normal AUC (92-125%). Afibrinogenemic patients
      demonstrated PG of 2-29% of normal and appeared to correlate with the type of
      mutation. Thrombin peak-height (57 +/- 16%) was reduced (not significant) in
      these patients and AUC was comparable to the reference (102 +/- 27%). FXIII
      deficient plasmas resulted in a reduced thrombin peak-height of 59 +/- 13% (P <
      0.05) and normal AUC (90 +/- 14%). Thrombin peak-height (P < 0.01) and plasmin
      potential (P < 0.05) were lower in the major bleeders compared with the minor
      bleeders. These results provided distinct TG and PG curves for each individual
      abnormality and differentiation of bleeding tendency was observed for thrombin
      and PG parameters. Prospective studies are warranted to confirm these
      retrospective results.

PMID- 22404436
TI  - Feasibility and safety of endoscopic ultrasound-guided fine needle aspiration of
      the pancreas in dogs.
AB  - BACKGROUND: Endoscopic ultrasound (EUS)-guided fine needle aspiration (EUS-FNA)
      has proven a useful and safe diagnostic tool for assessing pancreatic disease in
      human medicine. No information about pancreatic EUS-FNA is available in dogs.
      OBJECTIVES: To assess the feasibility and safety of pancreatic EUS-FNA in healthy
      dogs. ANIMALS: Thirteen beagles with a median body weight of 13.4 kg. METHODS:
      Experimental study. An ultrasound endoscope (insertion tube outer diameter 11.8
      mm) was used, and FNA was carried out with 19 G needles. The optimal puncture
      site was chosen with the aid of Doppler imaging. Complete clinicopathologic
      assessments including pain scoring and pancreas-specific lipase measurements were
      obtained before EUS as well as on day 1 and day 2 after EUS-FNA. RESULTS: The
      pancreatic body was identified in all dogs, the left lobe was clearly identified
      in 9/13 and appeared indistinctly marginated in 4/13 dogs, and the distal third
      of the right lobe could not be identified in 7/13 dogs. EUS-FNA was carried out
      in 12/13 dogs. Cellularity of smears was adequate for evaluation in 8/12 cases,
      in which samples were obtained transgastrically (n = 4) or transduodenally (n =
      4). All dogs recovered uneventfully and no clinical and laboratory abnormalities
      occurred during the 48 hour monitoring period after the procedure. CONCLUSION AND
      CLINICAL IMPORTANCE: Although the healthy canine pancreas is difficult to
      visualize in its entirety with EUS, pancreatic EUS-FNA with a 19 G needle is
      feasible in medium-sized dogs and can be considered a safe procedure. Its
      diagnostic usefulness should be evaluated in dogs with pancreatic disease.

PMID- 22404437
TI  - Accuracy of diagnostic tests for Helicobacter pylori in patients with peptic
      ulcer bleeding.
AB  - BACKGROUND AND AIMS: To assess the validity of biopsy-based tests (histology,
      culture, and urease test) and serology in detecting current H. pylori infection
      for the peptic ulcer patients who had gastric bleeding. METHODS: A total of 398
      peptic ulcer patients were enrolled and divided into two groups, according to the
      presence or absence of bleeding. The diagnosis for current H. pylori infection
      was verified using the gold standard combining individual H. pylori tests.
      Sensitivity, specificity, and positive and negative predictive values of the
      culture, Campylobacter-like organism (CLO) test (urease test), histology, and
      serology were compared. RESULTS: Of the total study population (N = 398), 157
      (39.4%) patients were categorized into the bleeding group. The sensitivities of
      the culture (40.0%) and CLO (85.0%) in the bleeding group were significantly
      lower than culture (58.1%) and CLO (96.4%) in the nonbleeding group (p = .012 and
      p < .001, respectively). In the bleeding group, the sensitivity of CLO (85.0%)
      was significantly lower than histology (92.5%) and serology (97.4%) (p = .013 and
      p = .002, respectively), which was not found in the nonbleeding group. The
      specificity of serology in the bleeding group (56.3%) was significantly lower
      than that of nonbleeding group (74.2%) (p = .038). Similarly, the specificity of
      serology was significantly lower than the other H. pylori tests in the bleeders.
      CONCLUSIONS: Bleeding decreased the sensitivity of H. pylori tests in patients
      with peptic ulcer, especially in urease test or culture. In contrast, histology
      was found to be a quite reliable test, regardless of the presence of bleeding.

PMID- 22404438
TI  - Predictive factors for improvement of atrophic gastritis and intestinal
      metaplasia after Helicobacter pylori eradication: a three-year follow-up study in
      Korea.
AB  - BACKGROUND AND AIMS: To date, data on the effects of anti-Helicobacter therapy on
      the improvement of atrophic gastritis (AG) and intestinal metaplasia (IM) have
      been conflicting. This study was performed to investigate whether eradication of
      H. pylori could lead to the improvement of AG and IM, and the prognostic factors
      associated with the improvement of AG and IM. METHODS: Four hundred patients
      consisting of H. pylori-negative (n = 116) and H. pylori-positive (n = 284)
      groups were followed up 1 and 3 years after initial H. pylori tests. Serum levels
      of pepsinogen (PG), bacteria, environmental factors, and genetic polymorphisms
      were determined. RESULTS: The grade of corpus atrophy decreased at 1 and 3 years
      after successful eradication (p < .001 and p = .033, respectively). However,
      there was no significant change in the IM in the antrum and in the corpus.
      Prediction factors for the improvement of corpus AG by H. pylori eradication were
      baseline low PG I/II ratio (<=3), high salt intake, and corpus-predominant
      gastritis. IM improvement was also associated with spicy food intake and high
      baseline grade of IM, in addition to these factors. In addition, IL-1B-511 C/T
      and IL-6-572 C/G alleles were found to inhibit IM improvement. However, H. pylori
      negative and noneradicated group did not show any significant change in AG or IM.
      CONCLUSION: Corpus AG was reversed by H. pylori eradication, and improvement of
      IM by H. pylori eradiation was more definite in patients with severe IM, low PG
      I/II ratio, and corpus-predominant gastritis, suggesting that H. pylori
      eradication is valuable even in severe cases.

PMID- 22404439
TI  - Non-invasive genotyping of Helicobacter pylori cagA, vacA, and hopQ from
      asymptomatic children.
AB  - BACKGROUND: Helicobacter pylori infection is usually acquired in childhood, but
      little is known about its natural history in asymptomatic children, primarily due
      to the paucity of non-invasive diagnostic methods. H. pylori strains harboring
      cagA and specific alleles of hopQ and vacA are associated with increased risk for
      gastric cancer. Many studies of H. pylori virulence markers in children have the
      bias that symptomatic subjects are selected for endoscopy, and these children may
      harbor the most virulent strains. Our aim is to genotype cagA, hopQ, and vacA
      alleles in stool DNA samples of healthy Colombian children residing in an area
      with high incidence of gastric cancer, to avoid selection bias resulting from
      endoscopy. METHODS: H. pylori status of 86 asymptomatic children was assessed by
      (13) C-urea breath test (UBT) and PCR. H. pylori 16S rRNA, cagA, hopQ, and vacA
      genes were amplified from stool DNA samples and sequenced. RESULTS: UBT was
      positive in 69 (80.2%) of 86 children; in stool DNA analysis, 78.3% were positive
      by 16S rRNA PCR. cagA, vacA, and hopQ were detected in 66.1%, 84.6%, and 72.3% of
      stool DNA samples from 16S rRNA-positive children. Of the children's DNA samples,
      which revealed vacA and hopQ alleles, 91.7% showed vacA s1 and 73.7% showed type
      I hopQ. Type I hopQ alleles were associated with cagA positivity and vacA s1
      genotypes (p < 0.0001). CONCLUSIONS: Using stool DNA samples, virulence markers
      of H. pylori were successfully genotyped in a high percentage of the asymptomatic
      infected children, revealing a high prevalence of genotypes associated with
      virulence. Type I hopQ alleles were associated with the presence of cagA and the
      vacA s1 genotype.

PMID- 22404441
TI  - Association of inflammation and cytotoxin-associated gene a positive strains of
      helicobacter pylori in cardiac syndrome x.
AB  - BACKGROUND: Cardiac syndrome X (CSX) is a condition in which patients have the
      pain of angina despite normal coronary angiogram. Helicobacter pylori (H. pylori)
      infection causes chronic inflammation which may play a pathogenic role in CSX. We
      surveyed the association of inflammation with H. pylori and its virulent strain
      (cytotoxin-associated gene A positive; CagA+) infections with CSX. MATERIAL AND
      METHODS: Sixty patients with CSX (38 women/22 men; mean age: 51.8 +/- 12.3) and
      60 age- and gender-matched healthy controls (39 women/21 men; mean age: 48.9 +/-
      6.3) were enrolled. Plasma samples were tested for the presence of IgG antibody
      to H. pylori using enzyme linked immunosorbent assay (ELISA) method. IgG-
      positive patients were determined by the presence of IgG antibody to CagA, also
      by ELISA method. Also, plasma levels of interleukin-6 (IL-6) and tumor necrosis
      factor-alpha (TNF-alpha) were measured by ELISA method. RESULTS: Patients with
      CSX were detected to have significantly higher plasma IL-6 and TNF-alpha level in
      comparison with normal controls (33.6 +/- 3.5 vs 3.2 +/- 0.4 and 24.2 +/- 2.3 vs
      3.1 +/- 0.4, respectively; p < 0.01). The plasma levels of these inflammatory
      factors in CgA+ were significantly higher than those in CagA- (CSX: IL-6: 43.05
      +/- 5.04 vs 23.97 +/- 4.58 and TNF-alpha: 31.43 +/- 3.13 vs 16.47 +/- 2.93,
      CONTROLS: IL-6: 3.52 +/- 1.39 vs 2.90 +/- 0.67 and TNF-alpha: 5.39 +/- 1.17 vs
      2.22 +/- 0.43, respectively; p < 0.05). CONCLUSION: The CagA+ strain of H.
      pylori, can not only be a trigger, and may also have a role via chronic
      inflammation in the pathogenesis of CSX.

PMID- 22404440
TI  - Serologic evidence that ascaris and toxoplasma infections impact inflammatory
      responses to Helicobacter pylori in Colombians.
AB  - BACKGROUND: Helicobacter pylori-infected children from coastal Tumaco, Colombia,
      have more parasitism, and adults have lower gastric cancer risk compared with
      high-altitude Pasto/Tuquerres residents. Because helminth and Toxoplasma gondii
      infections alter helicobacter gastritis in rodent models, we determined whether
      seropositivity to Ascaris lumbricoides or T. gondii was associated with Th2-IgG1
      or Th1-IgG2 responses to H. pylori. METHODS: Sera (240) from the two populations
      were evaluated for A. lumbricoides and T. gondii seropositivity and results
      correlated with IgE and IgG isotype responses to H. pylori. RESULTS: Most Tumaco
      children and adults were seropositive for A. lumbricoides (89%, 66%), T. gondii
      (59%, 98%), or both (45%, 66%). In contrast, seropositivity among Pasto/Tuquerres
      children was much lower (9%A. lumbricoides, 11%T. gondii, and 2% dual positive)
      but increased in adults (58%A. lumbricoides, 82%T. gondii, and 41% dual
      positive). A. lumbricoides seropositivity correlated with elevated IgE and anti
      inflammatory Th2-IgG1 responses to H. pylori, while T. gondiigondii
      seropositivity was linked to elevated IgE, pro-inflammatory Th1-IgG2, IgG3, and
      IgG4 responses to H. pylori. Individuals with high T. gondii titers had reduced
      Th1-IgG2, IgG3, and IgG4 responses to H. pylori. CONCLUSIONS: Results support
      regional differences for childhood parasitism and indicate A. lumbricoides and T.
      gondii infections may impact inflammatory responses to H. pylori and partially
      explain differences in gastric cancer risk in Colombia.

PMID- 22404442
TI  - Low efficacy of clarithromycin including sequential regimens for Helicobacter
      pylori infection.
AB  - BACKGROUND: Sequential treatment for Helicobacter pylori (H. pylori) appears to
      achieve a better eradication rate than triple therapy. However, most of the data
      have been reported from the Italy, and studies from different population are
      needed before it is recommended in clinical practice. The present study aimed to
      assess and compare the efficacy of two separate clarithromycin including
      sequential regimens in Turkey which is well known with high clarithromycin and
      metronidazole resistance to H. pylori. METHODS: Consecutive H. pylori -positive
      patients with non-ulcer dyspepsia were randomly allocated to one of the two
      sequential regimens; the first group was given lansoprazole 30 mg b.i.d. plus
      amoxicillin 1 g b.i.d. for the first week, followed by lansoprazole 30 mg b.i.d.,
      clarithromycin 500 mg b.i.d., and metronidazole 500 mg t.i.d. for the second week
      (LA-CM). The second arm was given the same regimen but tetracycline500 g q.i.d.
      instead of metronidazole (LA-CT). H. pylori was detected with urea breath test
      (UBT) and histology before enrollment. UBT was repeated at 6th weeks after
      treatment. RESULTS: A total of 200 patients were enrolled in groups and 179 of
      them completed their protocols. The cumulative per protocol ("PP") and intention
      to-treat ("ITT") eradication rates were 74.3% and 66.5% in all patients,
      respectively. Both "PP" (78.2% vs 70.1%) and "ITT" (72% vs 61%) eradication rates
      were better in LA-CT group than LA-CM group, but the differences were not
      statistically significant (p > .05). Both regimens were well tolerated, and the
      incidence of adverse effects was comparable. CONCLUSION: Two weeks clarithromycin
      including sequential regimens with metronidazole or tetracycline were not
      achieved acceptable eradication rates in Turkey.

PMID- 22404443
TI  - Effects of alpha tocopherol and ascorbic acid on Helicobacter pylori colonization
      and the severity of gastric inflammation.
AB  - BACKGROUND AND AIM: We aimed to evaluate the changes in histopathologic features,
      concentrations of vitamins C and E in gastric mucosa, and total antioxidant
      capacity of the body after ingestion of ascorbic acid and alpha tocopherol in
      patients with Helicobacter pylori. MATERIAL AND METHOD: Patients with H. pylori
      positive nonulcer dyspepsia were included in this study. Tissue samples were
      taken from the lesser and greater curvature in both prepyloric antrum and corpus
      for histopathologic examination and measurement of vitamins C and E
      concentrations. Blood samples were obtained for measurement of the total
      antioxidant capacity of the body. The patients were given vitamin C 500 mg BID
      and vitamin E 200 IU BID for 4 weeks orally. At the end of the 4th week, the
      initial procedures were repeated. Histopathologic examination of the tissue
      samples were carried out by two pathologists. RESULTS: The mean vitamins C and E
      concentrations in gastric mucosa at the 4th week were higher than those at the
      beginning (p = .000 and p = .006, respectively). Mean total antioxidant capacity
      of the body at the beginning and that at the 4th week were similar (p = .689). H.
      pylori intensity in the antrum at the beginning was higher than that at the 4th
      week for both pathologists (p = .007 and p = .039). Neutrophilic activity in the
      antrum at the beginning was higher than that at the 4th week for both
      pathologists (p = .000 and p = .025). Neutrophilic activity in the corpus at the
      beginning was higher than that at the 4th week for pathologist 1 (p = .033), and
      they were similar for pathologist 2 (p = .763). CONCLUSION: The findings that H.
      pylori intensity and neutrophilic activity decrease through increasing gastric
      ascorbic acid and alpha tocopherol concentrations suggest that supplementation
      with vitamins C and E increases the eradication rates via impairing the
      microenvironment created by the bacteria and facilitating the diffusion of
      antibiotics into gastric mucosa.

PMID- 22404444
TI  - Effects of cholesterol on Helicobacter pylori growth and virulence properties in
      vitro.
AB  - BACKGROUND: Colonization of the gastric mucosa by Helicobacter pylori is often
      associated with chronic gastric pathologies in humans. Development of disease
      correlates with the presence of distinct bacterial pathogenicity factors, such as
      the cag type IV secretion system (cag-T4SS), the vacuolating cytotoxin (VacA), or
      the ability of the bacteria to acquire and incorporate cholesterol from human
      tissue. MATERIALS AND METHODS: The in vitro growth of H. pylori requires media
      (Brucella broth) complemented with vitamins and horse serum or cyclodextrins,
      prepared as blood agar plates or liquid cultures. Liquid cultures usually show a
      slow growth. Here, we describe the successful growth of H. pylori strains 26695,
      P217, P12, and 60190 on serum-free media replacing serum components or
      cyclodextrins with a commercially available cholesterol solution. RESULTS: The
      effects of cholesterol as a substitute for serum or cyclodextrin were rigorously
      tested for growth of H. pylori on agar plates in vitro, for its general effects
      on bacterial protein synthesis (the proteome level), for H. pylori's natural
      competence and plasmid DNA transfer, for the production of VacA, and the general
      function of the cag-pathogenicity island and its encoded cag-T4SS. Generally,
      growth of H. pylori with cholesterol instead of serum supplementation did not
      reveal any restrictions in the physiology and functionality of the bacteria
      except for strain 26695 showing a reduced growth on cholesterol media, whereas
      strain 60190 grew more efficient in cholesterol- versus serum-supplemented liquid
      medium. CONCLUSIONS: The use of cholesterol represents a considerable option to
      serum complementation of growth media for in vitro growth of H. pylori.

PMID- 22404445
TI  - p27(kip1) upregulated by hnRNPC1/2 antagonizes CagA (a virulence factor of
      Helicobacter pylori)-mediated pathogenesis.
AB  - BACKGROUND AND AIMS: Infection by Helicobacter pylori is one of the major
      contributing factors of chronic active gastritis and peptic ulcer and is closely
      associated with the occurrence and progression of gastric cancer. CagA protein is
      a major virulence factor of H. pylori that interacts with SHP-2, a true oncogene,
      to interfere with cellular signaling pathways; CagA also plays a crucial role in
      promoting the carcinogenesis of gastric epithelial cells. However, currently, the
      molecular mechanisms of gastric epithelial cells that antagonize CagA
      pathogenesis remain inconclusive. METHODS: We showed that AGS gastric cancer
      cells transfected with CagA exhibited the inhibition of proliferation and
      increased activity of caspase 3/7 using two-dimensional gel electrophoresis and
      secondary mass spectrometry (MS/MS). RESULTS: It was found that the AGS gastric
      cancer cells stably expressing CagA displayed significantly increased the
      expression of 16 proteins, including hnRNPC1/2. Further analysis revealed that
      hnRNPC1/2 significantly boosted the expression of the p27(kip1) protein.
      CONCLUSION: Our data suggested that hnRNPC1/2 upregulates p27(kip1) expression
      and the subsequent suppression of cell proliferation and induction of apoptosis,
      thereby providing an important mechanism whereby gastric epithelial cells
      antagonize CagA-mediated pathogenesis.

PMID- 22404446
TI  - Systematic review and meta-analysis: Helicobacter pylori eradication therapy
      after simple closure of perforated duodenal ulcer.
AB  - BACKGROUND: The most common complications of peptic ulcer are bleeding and
      perforation. In many regions, definitive acid reduction surgery has given way to
      simple closure and Helicobacter pylori eradication. AIM: To perform a systematic
      review and meta-analysis to ask whether this change in practice is in fact
      justified. MATERIALS AND METHODS: A search on the Cochrane Controlled Trials
      Register, Medline, and Embase was made for controlled trials of duodenal ulcer
      perforation patients using simple closure method plus postoperative H. pylori
      eradication therapy versus simple closure plus antisecretory non-eradication
      therapy. The long-term results for prevention of ulcer recurrence were compared.
      RESULTS: The pooled incidence of 1-year ulcer recurrence in H. pylori eradication
      group was 5.2% [95% confidence interval (CI) of 0.7 and 9.7], which is
      significantly lower than that of the control group (35.2%) with 95% CI of 0.25
      and 0.45. The pooled relative risk was 0.15 with 95% CI of 0.06 and 0.37.
      CONCLUSIONS: Helicobacter pylori eradication after simple closure of duodenal
      ulcer perforation gives better result than the operation plus antisecretory non
      eradication therapy for prevention of ulcer recurrence. All duodenal ulcer
      perforation patients should be tested for H. pylori infection, and eradication
      therapy is required in all infected patients.

PMID- 22404447
TI  - Comparison of demographic characteristics and upper gastrointestinal endoscopy
      findings in HIV-positive, antiretroviral-treated patients with and without
      Helicobacter pylori coinfection.
AB  - OBJECTIVES: We evaluated demographic characteristics in HIV-positive patients
      receiving highly active antiretroviral therapy (HAART) who had upper
      gastrointestinal (UGI) symptoms requiring UGI endoscopy and compared the findings
      in patients with and without H. Pylori coinfection. METHODS: We prospectively
      observed all HIV-infected patients treated with antiretroviral therapy who
      underwent UGI endoscopy for the first time and were tested for H. pylori from
      January 2004 to December 2008. Data collected included the following:
      demographics (age, gender, ethnicity, body mass index [BMI], tobacco use, alcohol
      intake, and HIV risk behavior); comorbidity (viral hepatitis B or C, any organ
      dysfunction, or opportunistic disease); medication, including antibiotics, H2
      blockers, proton pump inhibitors, and NSAIDs; CD4 cell counts, viral load;
      symptoms; and endoscopic and histologic diagnoses (H. pylori determined by Giemsa
      staining). Patients were compared according to H. pylori status (presence vs
      absence). RESULTS: One hundred and forty-five patients were evaluated. Compared
      to patients without H. pylori infection (n = 97), those with H. pylori infection
      (n = 48) had a significantly higher CD4 cell count (p = .008), were more likely
      to be heterosexual (p = .047), had a higher BMI (p = .027), had a greater
      incidence of duodenal ulcers (p = .005), had lower viral loads (p < .01), were
      less likely to have received macrolide antibiotics in the last 3 months (p =
      .00), and had less comorbidity (p = .03). They were also more frequently of Black
      African than Caucasians. In multivariate analysis, being heterosexual and having
      a low viral load were independently associated with an increased risk of having
      H. Pylori coinfection. CONCLUSION: In the antiretroviral therapy era, HIV-H.
      pylori coinfection is associated with a greater incidence of duodenal ulcers and
      higher CD4 counts, higher BMI, less comorbidity, and less frequent use of
      macrolides.

PMID- 22404448
TI  - Maintenance of Helicobacter pylori eradication rates with triple therapy over 12
      years in a Spanish hospital.

PMID- 22404449
TI  - A novel model might predict the risk of chronic atrophic gastritis: a multicenter
      prospective study in China.
AB  - OBJECTIVE: To find a new way to predict the risk of chronic atrophic gastritis
      (CAG). MATERIAL AND METHODS: All the participants received endoscopy and
      histological examination as well as a standard questionnaire. Multivariate
      analysis was performed by logistic regression to build the CAG risk model. The
      accuracy was evaluated by 1418 subjects recruited from six medical centers. 63
      subjects received another endoscopy after 1-year follow-up and divided into three
      groups according to the comparison of the histological results (improved, no
      change and worse). RESULTS: The model showed relatively good discrimination, with
      an AUROC of 0.888 (95% CI 0.852-0.925). A final probability cut-off score of 0.73
      was used to predict the presence (>0.73) or absence of CAG (<=0.73). Sensitivity,
      specificity, PPV and NPV were 82.8%, 74.7%, 91.8% and 56%, respectively. The
      predicted results of 1418 subjects compared with the histological results were
      quite similar. There was a significant difference of the scores between three
      groups who were followed-up for 1 year (F = 3.248, p = 0.046). In multiple
      comparisons, a significant difference existed between Group A (the histological
      results had improved after 1-year follow-up) and Group C (the results were worse)
      (p = 0.019). CONCLUSIONS: This is the first demonstration of the use of a
      mathematical model for CAG risk screening. Endoscopy should be recommended to
      those who are positive according to the model, to detect CAG early and conserve
      medical resources. In those who have a high-risk score, closer follow-up is
      needed.

PMID- 22404450
TI  - Raalin, a transcript enriched in the honey bee brain, is a remnant of genomic
      rearrangement in Hymenoptera.
AB  - We identified a predicted compact cysteine-rich sequence in the honey bee genome
      that we called 'Raalin'. Raalin transcripts are enriched in the brain of adult
      honey bee workers and drones, with only minimum expression in other tissues or in
      pre-adult stages. Open-reading frame (ORF) homologues of Raalin were identified
      in the transcriptomes of fruit flies, mosquitoes and moths. The Raalin-like gene
      from Drosophila melanogaster encodes for a short secreted protein that is
      maximally expressed in the adult brain with negligible expression in other
      tissues or pre-imaginal stages. Raalin-like sequences have also been found in the
      recently sequenced genomes of six ant species, but not in the jewel wasp Nasonia
      vitripennis. As in the honey bee, the Raalin-like sequences of ants do not have
      an ORF. A comparison of the genome region containing Raalin in the genomes of
      bees, ants and the wasp provides evolutionary support for an extensive genome
      rearrangement in this sequence. Our analyses identify a new family of ancient
      cysteine-rich short sequences in insects in which insertions and genome
      rearrangements may have disrupted this locus in the branch leading to the
      Hymenoptera. The regulated expression of this transcript suggests that it has a
      brain-specific function.

PMID- 22404451
TI  - Synthesis and reactivity of solid-supported organotrifluoroborates in Suzuki
      cross-coupling.
AB  - Solid-supported organotrifluoroborates were prepared in high yields by ion
      exchange with Amberlyst resins. The reactivity of solid supported
      aryltrifluoroborates was evaluated in Suzuki-Miyaura couplings with numerous aryl
      bromide partners. Electron-rich and -poor substituents were tolerated on both
      substrates, providing yields up to 90%. Examples of alkyl-, alkenyl-, alkynyl-,
      and heteroaryltrifluoborates were also successfully cross-coupled to aryl
      halides.

PMID- 22404452
TI  - The phenotype and course of inflammatory bowel disease in UK patients of
      Bangladeshi descent.
AB  - BACKGROUND: We have tested the hypotheses that compared with local white
      Caucasians, UK-resident patients of Bangladeshi descent develop inflammatory
      bowel disease (IBD) at a younger age; more often have Crohn's disease than
      ulcerative colitis (UC); and have a more aggressive disease course. AIM: To test
      the hypotheses that compared to white Caucasian patients of English, Scottish or
      Welsh descent, patients of Bangladeshi descent develop IBD at a younger age; more
      often have Crohn's disease; and have a more aggressive disease course by
      screening case-records of these patients. METHODS: We screened the case-records
      of 132 Bangladeshi and 623 white Caucasian consecutive out-patients. We then
      matched each Bangladeshi to a patient of white Caucasian descent for age at
      diagnosis and disease duration. Data on migration status, phenotype, disease
      course, treatments and extra-intestinal manifestations and complications were
      obtained. RESULTS: No differences were seen in the adjusted age at diagnosis of
      IBD between Bangladeshi and white Caucasian patients. More Bangladeshis than
      white Caucasian patients (P < 0.01) were diagnosed with Crohn's disease than UC.
      Crohn's phenotype at diagnosis was similar in both groups. However, multivariate
      Cox logistic regression analyses showed that Bangladeshis developed perianal
      complications (HR [95% confidence interval CI] 8.6 [1.4, 53.1], P = 0.02), and
      received anti-TNFs (HR [95% CI] 3.0 [1.2, 7.7], P = 0.02) earlier and underwent
      surgery later (HR [95% CI] 0.4 [0.2, 0.9], P = 0.03) than white Caucasians. More
      Bangladeshis with UC had extensive disease (24/40 [60%]) than white Caucasians
      (16/49 [33%], P = 0.02). Overall, more Bangladeshis were anaemic and vitamin D
      deficient. CONCLUSIONS: Bangladeshi patients with IBD more frequently have
      Crohn's than UC. Bangladeshis with Crohn's more frequently develop perianal
      disease, have earlier medication escalation and undergo surgery later than white
      Caucasians. Bangladeshis have more extensive UC than white Caucasians. The
      relative contributions of genotype and environmental factors, including vitamin
      D, to these phenotypic differences require additional study.

PMID- 22404453
TI  - Genetic variant R952Q in LRP8 is associated with increased plasma triglyceride
      levels in patients with early-onset CAD and MI.
AB  - We previously identified a novel locus for plasma triglyceride (TG) levels on
      chromosome 1p31-32 by genome-wide linkage analysis in the GeneQuest population
      with familial and premature coronary artery disease (CAD). Here we tested a
      hypothesis that variants in LRP8, a gene that is under the 1p31-32 linkage peak
      and associated with risk of familial and premature CAD and increased platelet
      activation, are associated with TG levels. Seven tagSNPs that cover the entire
      LRP8 gene were characterized in 358 GeneQuest Caucasian probands. Only SNP R952Q
      (rs5174) was associated with TG levels (P-adj = 0.0016), and this finding was
      replicated in one other independent population of 134 patients with early-onset
      myocardial infarction (males <45; females <55; P-adj = 0.0098). TG levels were
      higher in the group with higher body mass index (BMI >= 25) than in the group
      with lower BMI (BMI < 25). The association was significant in the overweight
      group (P-adj = 0.0029) or in the smoking group (P-adj = 0.0004), but not in the
      group with normal BMI or without smoking history. These results suggest that
      genetic variant R952Q of LRP8 is associated with increased plasma TG levels in
      patients who are overweight and have premature CAD/MI and history of smoking.

PMID- 22404454
TI  - Formal intramolecular (4 + 1)-cycloaddition of dialkoxycarbenes: control of the
      stereoselectivity and a mechanistic portrait.
AB  - The stereoselective synthesis of 5-5, 6-5, and 7-5 fused O-heterocyclic compounds
      is reported. The key reaction is a formal intramolecular (4 + 1)-cycloaddition
      involving a dialkoxycarbene and an electron-deficient diene where the
      stereoselectivity is dependent on the length of the tether. An analysis of the
      stereochemical outcome of this reaction sheds light on its complex mechanistic
      picture. High-level calculations were used to support the proposed mechanistic
      portrait.

PMID- 22404455
TI  - Pharmacological treatment of heterotopic ossification following hip surgery: an
      update.
AB  - Heterotopic ossification is a frequent complication following total hip
      arthroplasty and acetabular surgery. Formation of ectopic lamellar bone in
      tissues that exhibit no potential for ossification can lead to associated pain
      and decrease in function. Prophylaxis and treatment protocols aim to reduce the
      incidence, by both the use of nonsteroidal anti-inflammatory drug (NSAID)
      regimens and localized radiotherapy. New therapeutic modalities including bone
      morphogenetic proteins (BMP) inhibitors like Noggin, BMP type 1 receptor
      inhibition, nuclear retinoic acid receptor-gamma agonists (RAR-gamma), and free
      radical scavengers are currently under investigation.

PMID- 22404456
TI  - Delineation of the etiology of a mass-like echo density in the left ventricle
      using three-dimensional transthoracic echocardiography.
AB  - Live/real time three-dimensional transthoracic echocardiography (3DTTE) provides
      an incremental value in the delineation of various cardiac pathologies. In this
      study, two-dimensional transthoracic echocardiography (2DTTE) of a 56-year-old
      patient showing a prominent echo density suggestive of a mass in the left
      ventricle probably attached to the ventricular side of the anterior mitral
      leaflet, is reported. Systematic cropping of the 3DTTE dataset showed the mass to
      be a calcified mitral strut chord viewed in cross section. This is well
      visualized in the accompanying movie clip. This case highlights the advantage of
      3DTTE in which the whole of the ventricle including the mitral valve apparatus is
      captured in the dataset facilitating cropping at any desired angulation.

PMID- 22404457
TI  - Post-operative cognitive dysfunction: more questions than answers?

PMID- 22404458
TI  - Parenthood in pediatric liver transplant patients.
AB  - Liver transplantation has become a universally accepted treatment for numerous
      congenital and acquired hepatic disorders that cause liver failure. Without liver
      transplantation, patients in their reproductive years are afflicted with
      oligospermia or azoospermia in men and amenorrhea in women, with infertility
      being a consequence in both sexes. The aim of this study is to describe our
      experiences concerning the parenthood of pediatric individuals who are successful
      recipients of liver transplantations coming into the reproductive years of life.
      We retrospectively analyzed data of 207 pediatric liver transplanted patients (96
      women, 111 men). Among them, three women conceived and delivered four babies, and
      two men admitted to paternity of two children after they all had been recipients
      of liver transplants. All female transplant recipients had received tacrolimus
      based immunosuppression. Preterm delivery was the most clinically important
      complication among these patients. Only one of the female patients experienced
      hypercalcemia during the pregnancy. None had any other complications such as
      hypertension, preeclampsia, cholestasis, or diabetes. There was no graft
      insufficiency, rejection, or birth defect. We concluded that maternity and
      paternity in liver transplant patients show normal outcomes even though this
      procedure occurs in childhood, and pregnancy did not seem to impair graft
      function in patients receiving immunosuppressive drugs.

PMID- 22404459
TI  - Local electronic structure and density of edge and facet atoms at Rh nanoclusters
      self-assembled on a graphene template.
AB  - The chemical and physical properties of nanoclusters largely depend on their
      sizes and shapes. This is partly due to finite size effects influencing the local
      electronic structure of the nanocluster atoms which are located on the nanofacets
      and on their edges. Here we present a thorough study on graphene-supported Rh
      nanocluster assemblies and their geometry-dependent electronic structure obtained
      by combining high-energy resolution core level photoelectron spectroscopy,
      scanning tunneling microscopy, and density functional theory. We demonstrate the
      possibility to finely control the morphology and the degree of structural order
      of Rh clusters grown in register with the template surface of graphene/Ir(111).
      By comparing measured and calculated core electron binding energies, we identify
      edge, facet, and bulk atoms of the nanoclusters. We describe how small
      interatomic distance changes occur while varying the nanocluster size,
      substantially modifying the properties of surface atoms. The properties of under
      coordinated Rh atoms are discussed in view of their importance in heterogeneous
      catalysis and magnetism.

PMID- 22404460
TI  - Clinical and microbiological evaluation of eight patients with isolated
      Achromobacter xylosoxidans.
AB  - Achromobacter xylosoxidans causes infections in patients with underlying
      disorders. The aim of this study was to evaluate Achromobacter xylosoxidans
      cases. Eight patients were included, 5 infections and 3 colonizations. Three of
      them survived and 2 died. The predisposing factor was catheter. Infection control
      measures could prevent infection.

PMID- 22404461
TI  - The effects of tropospheric ozone on net primary productivity and implications
      for climate change.
AB  - Tropospheric ozone (O(3)) is a global air pollutant that causes billions of
      dollars in lost plant productivity annually. It is an important anthropogenic
      greenhouse gas, and as a secondary air pollutant, it is present at high
      concentrations in rural areas far from industrial sources. It also reduces plant
      productivity by entering leaves through the stomata, generating other reactive
      oxygen species and causing oxidative stress, which in turn decreases
      photosynthesis, plant growth, and biomass accumulation. The deposition of O(3)
      into vegetation through stomata is an important sink for tropospheric O(3), but
      this sink is modified by other aspects of environmental change, including rising
      atmospheric carbon dioxide concentrations, rising temperature, altered
      precipitation, and nitrogen availability. We review the atmospheric chemistry
      governing tropospheric O(3) mass balance, the effects of O(3) on stomatal
      conductance and net primary productivity, and implications for agriculture,
      carbon sequestration, and climate change.

PMID- 22404462
TI  - Quantitative imaging with fluorescent biosensors.
AB  - Molecular activities are highly dynamic and can occur locally in subcellular
      domains or compartments. Neighboring cells in the same tissue can exist in
      different states. Therefore, quantitative information on the cellular and
      subcellular dynamics of ions, signaling molecules, and metabolites is critical
      for functional understanding of organisms. Mass spectrometry is generally used
      for monitoring ions and metabolites; however, its temporal and spatial resolution
      are limited. Fluorescent proteins have revolutionized many areas of biology-e.g.,
      fluorescent proteins can report on gene expression or protein localization in
      real time-yet promoter-based reporters are often slow to report physiologically
      relevant changes such as calcium oscillations. Therefore, novel tools are
      required that can be deployed in specific cells and targeted to subcellular
      compartments in order to quantify target molecule dynamics directly. We require
      tools that can measure enzyme activities, protein dynamics, and biophysical
      processes (e.g., membrane potential or molecular tension) with subcellular
      resolution. Today, we have an extensive suite of tools at our disposal to address
      these challenges, including translocation sensors, fluorescence-intensity
      sensors, and Forster resonance energy transfer sensors. This review summarizes
      sensor design principles, provides a database of sensors for more than 70
      different analytes/processes, and gives examples of applications in quantitative
      live cell imaging.

PMID- 22404463
TI  - Vacuolar transporters in their physiological context.
AB  - Vacuoles in vegetative tissues allow the plant surface to expand by accumulating
      energetically cheap inorganic osmolytes, and thereby optimize the plant for
      absorption of sunlight and production of energy by photosynthesis. Some
      specialized cells, such as guard cells and pulvini motor cells, exhibit rapid
      volume changes. These changes require the rapid release and uptake of ions and
      water by the vacuole and are a prerequisite for plant survival. Furthermore, seed
      vacuoles are important storage units for the nutrients required for early plant
      development. All of these fundamental processes rely on numerous vacuolar
      transporters. During the past 15 years, the transporters implicated in most
      aspects of vacuolar function have been identified and characterized. Vacuolar
      transporters appear to be integrated into a regulatory network that controls
      plant metabolism. However, little is known about the mode of action of these
      fundamental processes, and deciphering the underlying mechanisms remains a
      challenge for the future.

PMID- 22404464
TI  - Plant innate immunity: perception of conserved microbial signatures.
AB  - Plants and animals sense conserved microbial signatures through receptors
      localized to the plasma membrane and cytoplasm. These receptors typically carry
      or associate with non-arginine-aspartate (non-RD) kinases that initiate complex
      signaling networks cumulating in robust defense responses. In plants,
      coregulatory receptor kinases have been identified that not only are critical for
      the innate immune response but also serve an essential function in other
      regulatory signaling pathways.

PMID- 22404465
TI  - A new development: evolving concepts in leaf ontogeny.
AB  - Elucidation of gene regulatory networks (GRNs) underlying aspects of leaf
      development in multiple model species has uncovered surprisingly plastic
      regulatory architecture. The meticulously mapped network interactions in one
      model species cannot now be assumed to map directly onto a different species.
      Despite these overall differences, however, many modules do appear to be almost
      universal. Extrapolating findings across different model systems will demand
      great care but promises to reveal a rich tapestry of themes in GRN architecture
      and regulation. The purpose of this review is to approach the field of leaf
      development from the perspectives of the evolution of developmental systems that
      orchestrate leaf development.

PMID- 22404467
TI  - Regulation of seed germination and seedling growth by chemical signals from
      burning vegetation.
AB  - It is well known that burning of vegetation stimulates new plant growth and
      landscape regeneration. The discovery that char and smoke from such fires promote
      seed germination in many species indicates the presence of chemical stimulants.
      Nitrogen oxides stimulate seed germination, but their importance in post-fire
      germination has been questioned. Cyanohydrins have been recently identified in
      aqueous smoke solutions and shown to stimulate germination of some species
      through the slow release of cyanide. However, the most information is available
      for karrikins, a family of butenolides related to 3-methyl-2H-furo[2,3-c]pyran-2
      one. Karrikins stimulate seed germination and influence seedling growth. They are
      active in species not normally associated with fire, and in Arabidopsis they
      require the F-box protein MAX2, which also controls responses to strigolactone
      hormones. We hypothesize that chemical similarity between karrikins and
      strigolactones provided the opportunity for plants to employ a common signal
      transduction pathway to respond to both types of compound, while tailoring
      specific developmental responses to these distinct environmental signals.

PMID- 22404466
TI  - Control of Arabidopsis root development.
AB  - The Arabidopsis root has been the subject of intense research over the past
      decades. This research has led to significantly improved understanding of the
      molecular mechanisms underlying root development. Key insights into the
      specification of individual cell types, cell patterning, growth and
      differentiation, branching of the primary root, and responses of the root to the
      environment have been achieved. Transcription factors and plant hormones play key
      regulatory roles. Recently, mechanisms involving protein movement and the
      oscillation of gene expression have also been uncovered. Root gene regulatory
      networks controlling root development have been reconstructed from genome-wide
      profiling experiments, revealing novel molecular connections and models. Future
      refinement of these models will lead to a more complete description of the
      complex molecular interactions that give rise to a simple growing root.

PMID- 22404468
TI  - Plant defense against herbivores: chemical aspects.
AB  - Plants have evolved a plethora of different chemical defenses covering nearly all
      classes of (secondary) metabolites that represent a major barrier to herbivory:
      Some are constitutive; others are induced after attack. Many compounds act
      directly on the herbivore, whereas others act indirectly via the attraction of
      organisms from other trophic levels that, in turn, protect the plant. An enormous
      diversity of plant (bio)chemicals are toxic, repellent, or antinutritive for
      herbivores of all types. Examples include cyanogenic glycosides, glucosinolates,
      alkaloids, and terpenoids; others are macromolecules and comprise latex or
      proteinase inhibitors. Their modes of action include membrane disruption,
      inhibition of nutrient and ion transport, inhibition of signal transduction
      processes, inhibition of metabolism, or disruption of the hormonal control of
      physiological processes. Recognizing the herbivore challenge and precise timing
      of plant activities as well as the adaptive modulation of the plants' metabolism
      is important so that metabolites and energy may be efficiently allocated to
      defensive activities.

PMID- 22404469
TI  - Plant stem cell niches.
AB  - Multicellular organisms possess pluripotent stem cells to form new organs,
      replenish the daily loss of cells, or regenerate organs after injury. Stem cells
      are maintained in specific environments, the stem cell niches, that provide
      signals to block differentiation. In plants, stem cell niches are situated in the
      shoot, root, and vascular meristems-self-perpetuating units of organ formation.
      Plants' lifelong activity-which, as in the case of trees, can extend over more
      than a thousand years-requires that a robust regulatory network keep the balance
      between pluripotent stem cells and differentiating descendants. In this review,
      we focus on current models in plant stem cell research elaborated during the past
      two decades, mainly in the model plant Arabidopsis thaliana. We address the roles
      of mobile signals on transcriptional modules involved in balancing cell fates. In
      addition, we discuss shared features of and differences between the distinct stem
      cell niches of Arabidopsis.

PMID- 22404470
TI  - Epigenetic mechanisms underlying genomic imprinting in plants.
AB  - Genomic imprinting, the differential expression of an autosomal gene that is
      dependent on its parent of origin, has independently evolved in flowering plants
      and mammals. In both of these organism classes, imprinting occurs in embryo
      nourishing tissues-the placenta and the endosperm, respectively. It has been
      proposed that some imprinted genes control nutrient flow from the mother to the
      offspring. Genome-wide analyses of imprinted genes in plants have revealed that
      many imprinted genes are located in the vicinity of transposon or repeat
      sequences, implying that transposon insertions are associated with the evolution
      of imprinted loci. Imprinted expression of a number of genes is conserved between
      monocots and dicots, suggesting that long-term selection can maintain imprinted
      expression at some loci. In terms of epigenetic mechanisms, imprinted expression
      is largely controlled by an antagonistic action of DNA methylation and Polycomb
      group-mediated histone methylation in the vicinity of imprinted genes, whereby
      the position of such epigenetic modifications can determine whether a gene will
      be expressed mainly from either the maternally or paternally inherited alleles.

PMID- 22404471
TI  - Iron uptake, translocation, and regulation in higher plants.
AB  - Iron is essential for the survival and proliferation of all plants. Higher plants
      have developed two distinct strategies to acquire iron, which is only slightly
      soluble, from the rhizosphere: the reduction strategy of nongraminaceous plants
      and the chelation strategy of graminaceous plants. Key molecular components
      including transporters, enzymes, and chelators-have been clarified for both
      strategies, and many of these components are now thought to also function inside
      the plant to facilitate internal iron transport. Transporters for intracellular
      iron trafficking are also being clarified. A majority of genes encoding these
      components are transcriptionally regulated in response to iron availability.
      Recent research has uncovered central transcription factors, cis-acting elements,
      and molecular mechanisms regulating these genes. Manipulation of these molecular
      components has produced transgenic crops with enhanced tolerance to iron
      deficiency or with increased iron content in the edible parts.

PMID- 22404472
TI  - Photorespiration and the evolution of C4 photosynthesis.
AB  - C(4) photosynthesis is one of the most convergent evolutionary phenomena in the
      biological world, with at least 66 independent origins. Evidence from these
      lineages consistently indicates that the C(4) pathway is the end result of a
      series of evolutionary modifications to recover photorespired CO(2) in
      environments where RuBisCO oxygenation is high. Phylogenetically informed
      research indicates that the repositioning of mitochondria in the bundle sheath is
      one of the earliest steps in C(4) evolution, as it may establish a single-celled
      mechanism to scavenge photorespired CO(2) produced in the bundle sheath cells.
      Elaboration of this mechanism leads to the two-celled photorespiratory
      concentration mechanism known as C(2) photosynthesis (commonly observed in C(3)
      C(4) intermediate species) and then to C(4) photosynthesis following the
      upregulation of a C(4) metabolic cycle.

PMID- 22404473
TI  - Mechanisms of stomatal development.
AB  - The main route for CO(2) and water vapor exchange between a plant and the
      environment is through small pores called stomata. The accessibility of stomata
      and predictable division series that characterize their development provides an
      excellent system to address fundamental questions in biology. Stomatal cell-state
      transition and specification are regulated by a suite of transcription factors
      controlled by positional signaling via peptide ligands and transmembrane
      receptors. Downstream effectors include several members of the core cell-cycle
      genes. Environmentally induced signals are integrated into this essential
      developmental program to modulate stomatal development or function in response to
      changes in the abiotic environment. In addition, the recent identification of
      premitotic polarly localized proteins from both Arabidopsis and maize has laid a
      foundation for the future understanding of intrinsic cell polarity in plants.
      This review highlights the mechanisms of stomatal development through
      characterization of genes controlling cell-fate specification, cell polarity,
      cell division, and cell-cell communication during stomatal development and
      discusses the genetic framework linking these molecular processes with the
      correct spacing, density, and differentiation of stomata.

PMID- 22404474
TI  - Phosphoinositide signaling.
AB  - "All things flow and change...even in the stillest matter there is unseen flux
      and movement." Attributed to Heraclitus (530-470 BC), from The Story of
      Philosophy by Will Durant. Heraclitus, a Greek philosopher, was thinking on a
      much larger scale than molecular signaling; however, his visionary comments are
      an important reminder for those studying signaling today. Even in unstimulated
      cells, signaling pathways are in constant metabolic flux and provide basal
      signals that travel throughout the organism. In addition, negatively charged
      phospholipids, such as the polyphosphorylated inositol phospholipids, provide a
      circuit board of on/off switches for attracting or repelling proteins that define
      the membranes of the cell. This template of charged phospholipids is sensitive to
      discrete changes and metabolic fluxes-e.g., in pH and cations-which contribute to
      the oscillating signals in the cell. The inherent complexities of a constantly
      fluctuating system make understanding how plants integrate and process signals
      challenging. In this review we discuss one aspect of lipid signaling: the
      inositol family of negatively charged phospholipids and their functions as
      molecular sensors and regulators of metabolic flux in plants.

PMID- 22404475
TI  - Small molecules present large opportunities in plant biology.
AB  - Since the introduction of chemical genomics to plant biology as a tool for basic
      research, the field has advanced significantly. There are now examples of
      important basic discoveries that demonstrate the power and untapped potential of
      this approach. Given the combination of protein and small-molecule complexity,
      new phenotypes can be described through the perturbation of cellular functions
      that can be linked to growth and developmental phenotypes. There are now clear
      examples of overcoming functional redundancy in plants to dissect molecular
      mechanisms or critical pathways such as hormone signaling and dynamic
      intracellular processes. Owing to ongoing advances, including more sophisticated
      high-content screening and rapid approaches for target identification, the field
      is beginning to move forward. However, there are also challenges to improve
      automation, imaging, and analysis and provide chemical biology resources to the
      broader plant biology community.

PMID- 22404476
TI  - Genome-enabled insights into legume biology.
AB  - Legumes are the third-largest family of angiosperms, the second-most-important
      crop family, and a key source of biological nitrogen in agriculture. Recently,
      the genome sequences of Glycine max (soybean), Medicago truncatula, and Lotus
      japonicus were substantially completed. Comparisons among legume genomes reveal a
      key role for duplication, especially a whole-genome duplication event
      approximately 58 Mya that is shared by most agriculturally important legumes. A
      second and more recent genome duplication occurred only in the lineage leading to
      soybean. Outcomes of genome duplication, including gene fractionation and sub-
      and neofunctionalization, have played key roles in shaping legume genomes and in
      the evolution of legume-specific traits. Analysis of legume genome sequences also
      enables the discovery of legume-specific gene families and provides a framework
      for genome-wide association mapping that will target phenotypes of special
      importance in legumes. Translating genomic resources from sequenced species to
      less studied but still important "orphan" legumes will enhance prospects for
      world food production.

PMID- 22404477
TI  - The self regulatory effect of attentional control in modulating the relationship
      between attentional biases toward threat and anxiety symptoms in children.
AB  - The present study examined the associations between attentional biases to threat,
      attentional control and anxiety in a sample of children aged 9 to 14. It was
      hypothesised that the association between attentional biases toward threat and
      anxiety might be stronger when the ability to control attention is reduced. The
      study employed pictures of neutral, happy and angry facial expressions as they
      have greater ecological value compared to words. Children completed a dot-probe
      task measuring attentional biases toward such stimuli. They also completed the
      Spence child anxiety scale for anxiety symptoms and, for attentional control, the
      child version of the attention control scale measuring the ability to focus and
      shift attention. Results of a hierarchical regression analysis showed that
      attentional control significantly explained anxiety. Furthermore, the interaction
      between attentional control and attentional biases significantly explained
      anxiety level. These results indicate that attentional control moderates the
      relation between attentional biases toward threatening facial expressions and
      anxiety in children. Additionally, a discussion about a possible protective role
      of attentional control is provided.

PMID- 22404478
TI  - Effect of an integrated care programme on re-hospitalization of patients with
      chronic obstructive pulmonary disease.
AB  - BACKGROUND AND OBJECTIVE: Hospital admissions due to exacerbations of chronic
      obstructive pulmonary disease (COPD) have a major impact on disease progression
      and costs. We hypothesized that a 1-year integrated care (IC) programme
      comprising two components (patient-centred education+case management) would be
      effective in preventing COPD-related hospitalizations. METHODS: This was a
      retrospective longitudinal cohort study. Data were retrieved both from an
      administrative database in the province of Quebec (Canada), and from the medical
      records at two hospitals in Montreal. One hundred and eighty-nine COPD patients
      were randomly selected from registers at these centres, from 2004 to 2006.
      Patients in the intervention group underwent a programme comprising two
      components: patient -centred education-involving three group sessions of self
      management education that included one motivational interview and instruction in
      the use of a written action plan; and case management-involving scheduled follow
      up visits with access to a call centre. The intervention group was compared with
      a group receiving usual care (UC). The main outcome was COPD-related re
      hospitalizations, with length of hospital stay and emergency department (ED)
      visits being secondary outcomes. RESULTS: Logistic regression analysis with
      adjustment for covariates showed that there was a lower probability of re
      hospitalization over the follow-up year in the IC group compared with the UC
      group (odds ratio 0.44; 95% confidence interval 0.23-0.85). Subgroup analyses
      revealed that the IC programme prevented more COPD-related hospitalizations in
      women compared with men. There were no significant between-group differences in
      length of hospital stay or number of ED visits. CONCLUSIONS: An IC programme
      combining self-management education and case-management can decrease rates of
      COPD-related hospitalizations, particularly among women.

PMID- 22404479
TI  - A fungal endophyte reinforces population adaptive differentiation in its host
      grass species.
AB  - Hereditary symbioses between fungal endophytes and grasses are relatively recent
      in the history of plant life. Given < 80 million yr of co-evolution, symbioses
      are likely to have impacted plant microevolutionary rather than macroevolutionary
      processes. Therefore, we investigated the microevolutionary role of the fungal
      endophyte Neotyphodium lolii in the adaptive differentiation of its host species
      Lolium perenne. Endophyte frequency in 22 natural L. perenne populations was
      established across a water availability gradient. Adaptive differentiation among
      five populations, and between symbiotic (S) and nonsymbiotic (NS) plants, was
      examined in a glasshouse experiment under nonlimiting and limiting water
      conditions. Genetic differentiation was subsequently assessed among populations,
      and between S and NS individuals, using 14 simple sequence repeats (SSR).
      Symbiosis frequencies were positively correlated to water availability. Adaptive
      population differentiation occurred following a trade-off between biomass
      production under nonlimiting water conditions and survivorship under water
      stress. Endophytic symbiosis increased plant survival in xeric populations, and
      reinforced competitiveness in mesic populations. No genetic difference was
      detected between S and NS plants within populations. Therefore, we conclude that
      the endophyte relationship is responsible for these effects. Local adaptation of
      the host plant, appears to be supported by the fungal endophyte.

PMID- 22404481
TI  - Neurophysiology and therapeutic receptor targets for stress urinary incontinence.
AB  - Stress urinary incontinence is the most common type of urinary incontinence in
      women. Stress urinary incontinence involves involuntary leakage of urine in
      response to abdominal pressure caused by activities, such as sneezing and
      coughing. The condition affects millions of women worldwide, causing physical
      discomfort as well as social distress and even social isolation. This type of
      incontinence is often seen in women after middle age and it can be caused by
      impaired closure mechanisms of the urethra as a result of a weak pelvic floor or
      poorly supported urethral sphincter (urethral hypermobility) and/or a damaged
      urethral sphincter system (intrinsic sphincter deficiency). Until recently,
      stress urinary incontinence has been approached by clinicians as a purely
      anatomic problem as a result of urethral hypermobility requiring behavioral or
      surgical therapy. However, intrinsic sphincter deficiency has been reported to be
      more significantly associated with stress urinary incontinence than urethral
      hypermobility. Extensive basic and clinical research has enhanced our
      understanding of the complex neural circuitry regulating normal function of the
      lower urinary tract, as well as the pathophysiological mechanisms that might
      underlie the development of stress urinary incontinence and lead to the
      development of potential novel strategies for pharmacotherapy of stress urinary
      incontinence. Therapeutic targets include adrenergic and serotonergic receptors
      in the spinal cord, and adrenergic receptors at the urethral sphincter, which can
      enhance urethral reflex activity during stress conditions and increase baseline
      urethral pressure, respectively. This article therefore reviews the recent
      advances in stress urinary incontinence research and discusses the
      neurophysiology of urethral continence reflexes, the etiology of stress urinary
      incontinence and potential targets for pharmacotherapy of stress urinary
      incontinence.

PMID- 22404482
TI  - Magnetic resonance imaging for the differentiation of neoplastic, inflammatory,
      and cerebrovascular brain disease in dogs.
AB  - BACKGROUND: The reliability and validity of magnetic resonance imaging (MRI) for
      detecting neoplastic, inflammatory, and cerebrovascular brain lesions in dogs are
      unknown. OBJECTIVES: To estimate sensitivity, specificity, and inter-rater
      agreement of MRI for classifying histologically confirmed neoplastic,
      inflammatory, and cerebrovascular brain disease in dogs. ANIMALS: One hundred and
      twenty-one client-owned dogs diagnosed with brain disease (n = 77) or idiopathic
      epilepsy (n = 44). METHODS: Retrospective, multi-institutional case series; 3
      investigators analyzed MR images for the presence of a brain lesion with and
      without knowledge of case clinical data. Investigators recorded most likely
      etiologic category (neoplastic, inflammatory, cerebrovascular) and most likely
      specific disease for all brain lesions. Sensitivity, specificity, and inter-rater
      agreement were calculated to estimate diagnostic performance. RESULTS: MRI was
      94.4% sensitive (95% confidence interval [CI] = 88.7, 97.4) and 95.5% specific
      (95% CI = 89.9, 98.1) for detecting a brain lesion with similarly high
      performance for classifying neoplastic and inflammatory disease, but was only
      38.9% sensitive for classifying cerebrovascular disease (95% CI = 16.1, 67.0). In
      general, high specificity but not sensitivity was retained for MR diagnosis of
      specific brain diseases. Inter-rater agreement was very good for overall
      detection of structural brain lesions (kappa = 0.895, 95% CI = 0.792, 0.998, P <
      .001) and neoplastic lesions, but was only fair for cerebrovascular lesions
      (kappa = 0.299, 95% CI = 0, 0.761, P = .21). CONCLUSIONS AND CLINICAL IMPORTANCE:
      MRI is sensitive and specific for identifying brain lesions and classifying
      disease as inflammatory or neoplastic in dogs. Cerebrovascular disease in general
      and specific inflammatory, neoplastic, and cerebrovascular brain diseases were
      frequently misclassified.

PMID- 22404483
TI  - In vitro recapitulation of neural development using embryonic stem cells: from
      neurogenesis to histogenesis.
AB  - Embryonic stem (ES) cells have been successfully used over the past decade to
      generate specific types of neuronal cells. In addition to its value for
      regenerative medicine, ES cell culture also provides versatile experimental
      systems for analyzing early neural development. These systems are complimentary
      to conventional animal models, particularly because they allow unique
      constructive (synthetic) approaches, for example, step-wise addition of
      components. Here we review the ability of ES cells to generate not only specific
      neuronal populations but also functional neural tissues by recapitulating
      microenvironments in early mammalian development. In particular, we focus on
      cerebellar neurogenesis from mouse ES cells, and explain the basic ideas for
      positional information and self-formation of polarized neuroepithelium. Basic
      research on developmental signals has fundamentally contributed to substantial
      progress in stem cell technology. We also discuss how in vitro model systems
      using ES cells can shed new light on the mechanistic understanding of
      organogenesis, taking an example of recent progress in self-organizing
      histogenesis.

PMID- 22404484
TI  - Intraluminal high-dose-rate brachytherapy for palliation of dysphagia in cancer
      of the esophagus: initial experience at a single UK center.
AB  - Esophageal cancer tends to present with advanced disease, and the majority of
      patients are suitable only for palliative treatment at diagnosis. Dysphagia is
      the most common presenting symptom and significantly undermines quality of life.
      High-dose-rate intraluminal brachytherapy (ILBT) has been an option for the
      palliation of dysphagia for many years and has been used at our center since
      2006. Experience was presented in terms of improvement of dysphagia and survival.
      Patients were identified from the local radiotherapy database. Original treatment
      sheets and clinical notes were reviewed retrospectively to obtain treatment
      details, pretreatment and post-treatment dysphagia scores, and survival
      information. Between January 2006 and January 2010, 21 patients of median age 77
      years with a mean pretreatment dysphagia score of 2.5 underwent ILBT for
      esophageal cancer. All received 12 Gy in a single fraction. Thirteen (62%) had
      adenocarcinoma and eight (38%) squamous cell carcinoma. Four (19%) tumors were in
      the mid-esophagus and 17 (81%) in the lower esophagus. Eight had extension of
      tumor into the gastroesophageal junction. Seven patients (33%) received
      chemotherapy as first-line treatment prior to brachytherapy. Nineteen patients
      had clear documentation of dysphagia scores both pretreatment and post-treatment,
      and the improvement overall was significant (P= 0.04). Ten patients (53%) had an
      improvement in dysphagia score. Five of these (50%) went on to require further
      endoscopic intervention due to disease progression. Median duration of response
      was 4 months. Of the nonresponders, six (67%) went on to require further
      endoscopic intervention. No patients experienced documented toxicity aside from a
      short-lived acute esophagitis. Median survival from date of diagnosis was 12
      months and from treatment date was 5 months (1-32 months). In our series of
      elderly patients with significant dysphagia, ILBT was a well-tolerated and
      effective treatment. It should be considered as a palliative option in esophageal
      cancer.

PMID- 22404485
TI  - Quality of life in adult patients with haemophilia--a single centre experience
      from Sweden.
AB  - Increased or maintained health and quality of life (HRQoL) are essential goals in
      health care among patients with a chronic disease. To gain an understanding of
      HRQoL in patients with haemophilia at the Haemophilia Treatment Centre in Malmo,
      Sweden, patients seen from 2004-2008 were asked to complete the Short form Health
      Survey, SF-36, also answering to what extent haemophilia, physically and
      mentally, interferes with their daily life at their annual check-up. Data were
      extracted from the UMAS Haemophilia Database. Interference of haemophilia in
      daily life was estimated using a Visual Analogue Scale. A total of 105/144
      haemophilia patients were included in the study (73%); 28 mildly, 21 moderately
      and 56 severely affected. The median age of patients at study entry was 44.0
      years (range 18-84 years). The comparison of SF-36 data of Swedish haemophilia
      patients with the general Swedish male population yielded no significant
      differences in age groups 15-24, 25-34 and 65-74 years. Patients in age groups 35
      44 years, 45-54 years and 55-64 years were significantly impaired in some of
      their HRQoL domains. For severely affected patients who filled in SF-36 over a
      period of 5 years no statistical differences in HRQoL were found. For patients
      undergoing orthopaedic surgery HRQoL increased in most SF-36 domains. Patients
      reported in general on the VAS that they feel 'somehow' interfered in their daily
      life due to haemophilia. The results indicate a need for continuous monitoring of
      HRQoL to identify an increased need of care in the ageing haemophilia population.

PMID- 22404486
TI  - High-dose rabeprazole-amoxicillin dual therapy and rabeprazole triple therapy
      with amoxicillin and levofloxacin for 2 weeks as first and second line rescue
      therapies for Helicobacter pylori treatment failures.
AB  - BACKGROUND: H. pylori eradication failures are difficult to treat and rescue
      therapies often consist of complex treatment regimens. AIM: To determine an
      effective and practical rescue therapeutic strategy for H. pylori treatment
      failures using two consecutive regimens: first rescue therapy - rabeprazole 20 mg
      t.d.s. and amoxicillin 1 g t.d.s. for 2 weeks and for failures a further second
      rescue therapy - rabeprazole 20 mg b.d., levofloxacin 500 mg b.d., amoxicillin 1
      g b.d. for a further 2 weeks. METHODS: Consecutive patients who failed the proton
      pump inhibitor (PPI) 1-week triple therapy were recruited for the study. H.
      pylori status was determined by a C(13) urea breath test. RESULTS: One hundred
      and forty-nine patients received the first rescue therapy. Seven were not
      compliant to medication/defaulted follow-up. Eradication success- first rescue
      therapy: per protocol (PP) analysis-107/142 (75.4%) (95% CI (68.3-82.4%) and
      intention to treat (ITT) analysis-107/149 (71.8%) 95% CI (64.6-79.0%). Thirty-one
      of 35 patients who failed the first rescue therapy received the second rescue
      therapy. All were compliant with medications. Eradication success- PP and ITT was
      28/31 (90.3%) 95% CI (74.2-98.0%). The cumulative eradication rate using both
      rescue therapies: PP analysis- 135/138 (97.8%) 95% CI: (93.8-99.6%), ITT analysis
      135/149 (90.6%) 95% CI: (84.7-94.8%). CONCLUSIONS: A 2-week high dose PPI
      amoxicillin dual therapy followed by a PPI-amoxicillin-levofloxacin triple
      therapy were highly successful in achieving eradication in H. pylori treatment
      failures.

PMID- 22404487
TI  - Detection of antibodies against the non-calcium-dependent epitopes of desmoglein
      3 in pemphigus vulgaris and their pathogenic significance.
AB  - BACKGROUND: Antidesmoglein (anti-Dsg) 3 serum antibody titres are usually
      correlated with the disease activity of pemphigus vulgaris (PV), but some
      patients retain high titres even in remission. OBJECTIVES: The aim of our study
      was to determine whether anti-Dsg3 antibodies in PV sera recognized calcium
      (Ca(2+) )-dependent or non-Ca(2+) -dependent epitopes, and to evaluate their
      pathogenicity. METHODS: Dsg3 baculoprotein-coated enzyme-linked immunosorbent
      assay (ELISA) plates were treated with 0.5 mmol L(-1) ethylenediaminetetraacetic
      acid (EDTA). The binding ability of anti-Dsg3 monoclonal antibodies (mAbs) was
      analysed. Eight of the 83 patients with PV who were screened had elevated Dsg3
      ELISA index values > 00 in remission. The binding ability of these PV sera was
      analysed. We evaluated the pathogenicity of anti-Dsg3 serum antibodies against
      the non-Ca(2+) -dependent epitopes using a dissociation assay. RESULTS: The
      reactivity of pathogenic anti-Dsg3 mAbs against the Ca(2+) -dependent epitopes
      diminished markedly in the EDTA-treated ELISA, whereas no such reduction was
      observed in mAbs against the non-Ca(2+) -dependent epitopes. The sera of all the
      patients contained antibodies against both Ca(2+) -dependent and non-Ca(2+) 
      dependent epitopes. In six out of the eight patients, the ratio of antibodies
      against Ca(2+) -dependent to non-Ca(2+) -dependent epitopes decreased in
      remission. EDTA-treated Dsg3 baculoproteins adsorbed anti-Dsg3 serum antibodies
      against the non-Ca(2+) -dependent epitopes, but the remnant PV antibodies
      retained the ability to induce acantholysis in the dissociation assay.
      CONCLUSIONS: We have established an assay to measure indirectly the titres of
      anti-Dsg3 serum antibodies against the Ca(2+) -dependent epitopes, based on the
      differences between EDTA-untreated and EDTA-treated ELISA index values, as a
      routine laboratory test to reflect the pathogenic anti-Dsg3 serum antibody titres
      more accurately.

PMID- 22404488
TI  - Selective detection of the reduced form of glutathione (GSH) over the oxidized
      (GSSG) form using a combination of glutathione reductase and a Tb(III)-cyclen
      maleimide based lanthanide luminescent 'switch on' assay.
AB  - The synthesis of a novel Tb(III) luminescent probe for the detection of thiols is
      presented. The probe 1.Tb, possessing a maleimide moiety, as its sulfhydryl
      acceptor, was poorly emitting in aqueous pH 7 solution in the absence of a thiol.
      However, upon addition of thiols such as glutathione (GSH), large enhancements
      were observed, particularly within the physiological pH range. In contrast no
      enhancements were observed in the presence of the oxidized form of glutathione
      (GSSG), except in the presence of the enzyme glutathione reductase and NADPH
      which enabled 1.Tb to be used to observe the enzymatic reduction of GSSG to GSH
      in real time.

PMID- 22404489
TI  - Functional interactions between members of the REPAT family of insect pathogen
      induced proteins.
AB  - Studies on the transcriptional response to pathogens in the insect larval gut
      have shown the regulation of several genes after the infection. Repat (REsponse
      to PAThogens) genes were first identified in Spodoptera exigua midgut as being up
      regulated in response to the exposure to Bacillus thuringiensis toxins and
      baculovirus. Recently, new members of the REPAT family showed a constitutive up
      regulation in a B. thuringiensis-resistant population. Based on a yeast two
      hybrid screening, we have detected the interaction of REPAT1 with other members
      of the REPAT family, leading to the discovery of a new member: REPAT8. The
      functional role of this interaction was shown by following the changes of the
      subcellular localization of REPAT1 in the presence of REPAT8. REPAT1 alone was
      localized exclusively in the cytoplasm, while the presence of REPAT8 led to the
      migration of REPAT1 to the nucleus. Finally, analysis of the expression pattern
      of eight REPAT members has shown that B. thuringiensis-related treatments (Cry1Ca
      toxin, XentariTM product and an acrystalliferous strain) induced a general up
      regulation of repat genes, especially of repat2. In contrast, no significant
      effect was detected after treatment with Escherichia coli or Enterococcus sp., or
      by the presence of microbiota in the midgut. The results suggest that the
      different repat genes play different roles in response to pathogens.

PMID- 22404491
TI  - Sampling populations of humans across the world: ELSI issues.
AB  - There are an increasing number of population studies collecting data and samples
      to illuminate gene-environment contributions to disease risk and health. The
      rising affordability of innovative technologies capable of generating large
      amounts of data helps achieve statistical power and has paved the way for new
      international research collaborations. Most data and sample collections can be
      grouped into longitudinal, disease-specific, or residual tissue biobanks, with
      accompanying ethical, legal, and social issues (ELSI). Issues pertaining to
      consent, confidentiality, and oversight cannot be examined using a one-size-fits
      all approach-the particularities of each biobank must be taken into account. It
      remains to be seen whether current governance approaches will be adequate to
      handle the impact of next-generation sequencing technologies on communication
      with participants in population biobanking studies.

PMID- 22404490
TI  - The tension between data sharing and the protection of privacy in genomics
      research.
AB  - Next-generation sequencing and global data sharing challenge many of the
      governance mechanisms currently in place to protect the privacy of research
      participants. These challenges will make it more difficult to guarantee anonymity
      for participants, provide information to satisfy the requirements of informed
      consent, and ensure complete withdrawal from research when requested. To move
      forward, we need to improve the current governance systems for research so that
      they are responsive to individual privacy concerns but can also be effective at a
      global level. We need to develop a system of e-governance that can complement
      existing governance systems but that places greater reliance on the use of
      technology to ensure compliance with ethical and legal requirements. These new
      governance structures must be able to address the concerns of research
      participants while at the same time ensuring effective data sharing that promotes
      public trust in genomics research.

PMID- 22404492
TI  - A combination of two pseudoaneurysms due to severe endocarditis after cardiac
      surgery.

PMID- 22404493
TI  - Expedient construction of the [7-5-5] all-carbon tricyclic core of the
      Daphniphyllum alkaloids daphnilongeranin B and daphniyunnine D.
AB  - A synthetic strategy for the construction of the [7-5-5] all-carbon tricyclic
      core of numerous calyciphylline A-type Daphniphyllum alkaloids has been developed
      using a key intramolecular Pauson-Khand reaction. A subsequent base-mediated
      double-bond migration and a regio- and stereoselective radical late stage allylic
      oxygenation provide access to the substitution patterns of daphnilongeranin B and
      daphniyunnine D.

PMID- 22404494
TI  - Comparative evaluation of two isobaric labeling tags, DiART and iTRAQ.
AB  - Isobaric tags have broad applications in both basic and translational research,
      as demonstrated by the widely used isobaric tag for relative and absolute
      quantitation (iTRAQ). Recent results from large-scale quantitative proteomics
      projects, however, indicate that protein quantification by iTRAQ is often biased
      in complex biological samples. Here, we report the application of another
      isobaric tag, deuterium isobaric amine reactive tag (DiART), for quantifying the
      proteome of Thermoanaerobacter tengcongensis (T. tengcongensis), a thermophilic
      bacterium first discovered in China. We compared the performance of DiART with
      iTRAQ from several different aspects, including their fragmentation mechanisms,
      the number of identified proteins, and the accuracy of quantification. Our
      results revealed that, as compared with iTRAQ, DiART yielded significantly
      stronger reporter ions, which did not reduce the number of identifiable peptides,
      but improved the signal-to-noise ratio (S/N) for quantification. Remarkably, we
      found that, under identical chromatography and mass spectrometry (MS) conditions,
      DiART exhibited less reporter ions ratio compression than iTRAQ, probably due to
      more reporter ions with higher intensities produced by DiART labeling. Taken
      together, we demonstrate that DiART is a valuable alternative of iTRAQ with
      enhanced performance for quantitative proteomics.

PMID- 22404495
TI  - In vivo phycocyanin flourometry as a potential rapid screening tool for
      predicting elevated microcystin concentrations at eutrophic lakes.
AB  - Current approaches for assessing human health risks associated with cyanotoxins
      often rely on the quantification of microcystin. Significant limitations of
      current approaches are cost and time to obtain a result. To address these
      challenges, a numerical index for screening microcystin risks above the World
      Health Organization's (WHO) low-risk threshold for microcystin was developed for
      eutrophic Midwestern U.S. lakes based on water quality results from 182 beach
      water samples collected from seven Ohio lakes. In 48 (26.4%) samples we observed
      microcystin concentrations as measured by ELISA that exceeded the 4 MUg/L
      microcystin threshold. A multivariable logistic regression model using practical
      real-time measures of in vivo phycocyanin (by fluorometry) and secchi depth was
      constructed to estimate the probability of a beach sample exceeding 4 MUg/L
      microcystin. The final model achieved statistical significance (p = 0.030) as
      well as good calibration (as measured by the goodness-of-fit test comparing
      observed to expected counts within deciles of risk based on the model, p = 0.329)
      and discrimination (as indicated by the area under the receiver-operator-curve
      (0.795)). These results demonstrate two rapid and practical measures of
      recreational water quality are effective in identifying "at risk" lake conditions
      warranting additional management (e.g., advisory and/or advanced testing).

PMID- 22404496
TI  - Measuring the effects of sevoflurane on electroencephalogram using sample
      entropy.
AB  - BACKGROUND: Monitoring the effect of anesthetic drugs on the neural system is a
      major ongoing challenge for anesthetists. During the past few years, several
      electroencephalogram (EEG)-based methods such as the response entropy (RE) as
      implemented in the Datex-Ohmeda M-Entropy Module have been proposed. In this
      paper, sample entropy is used to quantify the predictability of EEG series, which
      could provide an index to show the effect of sevoflurane anesthesia. The dose
      response relation of sample entropy is compared with that of RE. METHODS: EEG
      data from 21 subjects is collected during the induction of general anesthesia
      with sevoflurane. The sample entropy is applied to the EEG recording.
      Pharmacokinetic-pharmacodynamic modeling and prediction probability statistic are
      used to evaluate the efficiency of sample entropy in comparison with RE. RESULTS:
      Both methods track the gross changes in EEG, especially the occurrence of burst
      suppression pattern at high doses of anesthetics. However, our method produces
      faster reaction to transients in EEG during the induction of anesthesia as
      indicated from the pharmacokinetic and pharmacodynamic modeled parameters and
      analysis around the point of loss of consciousness. Also, sample entropy
      correlated more closely with effect-site sevoflurane concentration than the RE.
      In addition, our proposed method exhibits greater resistance to noise in the EEG
      signals. CONCLUSION: The results demonstrate that sample entropy can estimate the
      sevoflurane drug effect on the EEG more effectively than the commercial RE index
      with a stronger noise resistance.

PMID- 22404497
TI  - An unusual manifestation of post-transplant lymphoproliferative disorder in the
      lip after pediatric heart transplantation.
AB  - PTLD is a serious and frequently observed complication after solid organ
      transplantation. We present a six-yr-old girl with a rapidly growing, solid tumor
      of the lip four yr after orthotopic heart transplantation, which was classified
      as monomorphic PTLD with the characteristics of a diffuse large B-cell lymphoma.
      Treatment with reduction in immunosuppression, ganciclovir, and anti B-cell
      monoclonal antibody (rituximab) resulted in full remission since 12 months. To
      the best of our knowledge, this report is the first description of PTLD in the
      lip in a pediatric patient after heart transplantation in the English literature.

PMID- 22404499
TI  - Alcohol, tobacco and illicit drug use among six culturally diverse communities in
      Sydney.
AB  - INTRODUCTION AND AIMS: A survey was conducted in 2004-2005 to investigate the
      risk of drug-related harm among Chinese, Vietnamese, Italian, Pasifika, Arabic
      speaking and Spanish-speaking communities in Sydney. DESIGN AND METHODS: A self
      completion questionnaire, available in six languages, was distributed by
      bilingual field staff. A representative multistage clustered sampling design was
      used. Comparisons were made with the New South Wales general population using the
      results from the 2004 National Drug Strategy Household Survey. RESULTS: The
      obtained sample was 2212 respondents; 50% completed the questionnaire in English.
      Daily tobacco use was higher than the general population among Vietnamese men
      (30%), Italian men (22%) and Pasifika men and women (25%). Reported use of
      alcohol and other drugs was lower than the general population in all six surveyed
      communities. Of the six communities, Pasifika had the highest rate of short-term
      risky drinking (22%). DISCUSSION AND CONCLUSIONS: Smoking cessation programs
      should prioritise communities with higher or equal rates of daily smokers
      compared with the wider New South Wales population. Focus areas vary between the
      communities, and include increasing help seeking and improving quitting success
      rates. Short-term risky drinking was not as prevalent among the surveyed
      communities; however, results suggest a need for prevention targeting Pasifika
      communities. Understanding the prevalence of substance use among culturally and
      linguistically diverse communities provides a crucial foundational component in
      developing culturally sensitive prevention and treatment programs. These results
      demonstrate the need for programs to be tailored to the needs and contexts of
      particular communities, rather than treating those from diverse backgrounds as
      one homogenous group.

PMID- 22404500
TI  - Everolimus: preventing organ rejection in adult kidney transplant recipients.
AB  - INTRODUCTION: Kidney transplantation is the treatment of choice for patients with
      end-stage renal failure, and their survival after transplantation is gradually
      improving. Everolimus (EVL) is a mammalian target of rapamycin inhibitor,
      providing a safe and effective immunosuppressive regime after kidney
      transplantation. AREAS COVERED: The objective of this review is to summarize the
      clinical efficacy and safety of the EVL-based immunosuppressive regimen by
      analyzing peer-review reports and ongoing trials of its use after kidney
      transplantation in adult patients. EXPERT OPINION: Judging by the more recent
      trials, it seems that EVL, in association with calcineurin inhibitor (CNI)
      minimization, provides a well-tolerated regimen with a low risk of rejection and
      good graft function. Such regimens have been investigated intensively and should
      be preferable to complete elimination of CNI. In addition, future clinical
      studies should explore whether the pleiotropic effects of EVL are beneficial in
      the long term, leading to a reduction of cardiovascular diseases and de-novo
      malignancies.

PMID- 22404501
TI  - Intraoral desmoplastic fibroma: a manifestation of tuberous sclerosis.
AB  - Desmoplastic fibroma (DF) is a benign but locally aggressive tumor usually
      recognized as an intraosseous counterpart of soft tissue fibromatosis in both
      gnathic and extra-gnathic sites. The most common site is mandible followed by
      pelvis and long bones. Maxilla has been reported to be involved very rarely.
      Desmoplastic fibroma is recently being considered to be one of the oral
      manifestations of tuberous sclerosis rather than a coincidental finding. We
      report an unusual case of a girl with a previous diagnosis of tuberosclerosis who
      presented at 8 years with an oral lesion diagnosed as desmoplastic fibroma.

PMID- 22404502
TI  - Management trends, angioembolization performance and multiorgan injury indicators
      of renal trauma from Japanese administrative claims database.
AB  - OBJECTIVES: To show the characteristics and therapeutic trends of renal trauma in
      Japan using a nationwide database. METHODS: All renal trauma cases from the
      Diagnosis Procedure Combination database during 6 months of each year from 2006
      to 2008 were included in the analysis. The following variables were considered:
      demographics, ambulance use, comorbid trauma, interventions, mechanism of injury
      and the Abbreviated Injury Scale. Patients were divided into two groups by trauma
      range: limited to rib, abdomen and pelvis (group A) or more extended (including
      supradiaphragmatic regions or lower extremities; group B). Rib fracture impact
      was assessed as a predictor of comorbid organ trauma. The incidences of
      angioembolization failure and nephrectomy were also evaluated. RESULTS: A total
      of 1505 renal trauma cases (1014 and 491 in groups A and B, respectively) were
      identified. Comorbid trauma in the liver, spleen and lumbar/pelvic fractures were
      7.4%, 5.6% and 5.1% in group A and 24.0%, 11.2% and 17.5% in group B,
      respectively. The rates of angioembolization (and its failure proportion),
      nephrectomy, transfusion and mortality were 7.9% (12.5%), 3.3%, 15.6% and 1.1% in
      group A, and 17.1% (11.9%), 2.6%, 28.3% and 8.1% in group B, respectively. Risks
      of coincident traumas in the liver, spleen and pelvic fracture were 2.23, 2.35
      and 2.72 times higher if a rib fracture was observed. The incidences of renal
      trauma and nephrectomy (per 100 000 person-years) were estimated as 2.06 and
      0.063, respectively. CONCLUSIONS: Angioembolization failure is not rare, and
      nephrectomy is an important last resort. Patients with comorbid rib fracture
      should be explored for coincident traumas.

PMID- 22404503
TI  - Neuronal subtype specification in the cerebellum and dorsal hindbrain.
AB  - In the nervous system, there are hundreds to thousands of neuronal cell types
      that have morphologically, physiologically, and histochemically different
      characteristics and this diversity may enable us to elicit higher brain function.
      A better understanding of the molecular machinery by which neuron subtype
      specification occurs is thus one of the most important issues in brain science.
      The dorsal hindbrain, including the cerebellum, is a good model system to study
      this issue because a variety of types of neurons are produced from this region.
      Recently developed genetic lineage-tracing methods in addition to gene-transfer
      technologies have clarified a fate map of neurons produced from the dorsal
      hindbrain and accelerated our understanding of the molecular machinery of
      neuronal subtype specification in the nervous system.

PMID- 22404504
TI  - Delivery of Echinococcus granulosus antigen EG95 to mice and sheep using
      recombinant vaccinia virus.
AB  - The tapeworm Echinococcus granulosus is the causative agent of hydatid disease
      and affects sheep, cattle, dogs and humans worldwide. It has a two-stage life
      cycle existing as worms in the gut of infected dogs (definitive host) and as
      cysts in herbivores and humans (intermediate host). The disease is debilitating
      and can be life threatening where the cysts interfere with organ function.
      Interruption of the hydatid life cycle in the intermediate host by vaccination
      may be a way to control the disease, and a protective oncosphere antigen EG95 has
      been shown to protect animals against challenge with E. granulosus eggs. We
      explored the use of recombinant vaccinia virus as a delivery vehicle for EG95.
      Mice and sheep were immunized with the recombinant vector, and the result
      monitored at the circulating antibody level. In addition, sera from immunized
      mice were assayed for the ability to kill E. granulosus oncospheres in vitro.
      Mice immunized once intranasally developed effective oncosphere-killing antibody
      by day 42 post-infection. Antibody responses and oncosphere killing were
      correlated and were significantly enhanced by boosting mice with either EG95
      protein or recombinant vector. Sheep antibody responses to the recombinant vector
      or to EG95 protein mirrored those in mice.

PMID- 22404505
TI  - Human papillomavirus (HPV) infection and the risk of esophageal squamous cell
      carcinoma.
AB  - There is currently no consensus on the relationship between human papillomavirus
      (HPV) infection and the pathogenic process of esophageal squamous cell carcinoma
      (ESCC). Therefore, a retrospective study was performed to explore the association
      between HPV infection and ESCC, where 225 patients with diagnosed ESCC and 224
      matched controls were enrolled in the study and stratified according to smoking
      and alcohol consumption. Enzyme-linked immunosorbent assay was used to determine
      seropositivity to HPV by the detection of either IgG or IgM anti-HPV antibodies.
      In the non-smoking and non-alcohol-consuming subgroup, the incidence of ESCC of
      HPV seropositive subjects was similar with that of HPV seronegative subjects (P=
      0.737, odds ratio [OR] 1.14, 95% confidence interval [CI] 0.54-2.40). However, in
      the smoking subgroup, there was a significant difference in the incidence of ESCC
      between HPV seropositive subjects and HPV seronegative subjects (P= 0.009, OR
      2.22, 95% CI 1.22-4.04). In addition, there was a significantly higher
      association of the development of ESCC in HPV seropositive patients that smoke
      and drink than those that do not (P < 0.001, OR 10.31, 95% CI 4.04-26.29).
      Therefore, HPV infection is not an independent risk factor for developing ESCC in
      the non-smoking and non-alcohol-consuming group. For smokers, however, HPV
      infection increases the risk of the incidence of ESCC.

PMID- 22404506
TI  - Systematic review of efficacy of nutraceuticals to alleviate clinical signs of
      osteoarthritis.
AB  - BACKGROUND: Various treatments of osteoarthritis (OA) have been described,
      including use of nutraceuticals. OBJECTIVES: To review systematically the
      literature about the effects of nutraceuticals on clinical signs of pain or
      abnormal locomotion in horses, dogs, and cats, and to discuss methodological
      aspects of trials and systematic reviews. METHODS: A systematic search of
      controlled trials evaluating the impact of nutraceuticals on OA in horses, dogs,
      and cats was performed, using Medline, CAB Abstracts, and Google Scholar.
      Scientific evidence was evaluated by means of criteria proposed by the Food and
      Drug Administration (FDA), and a scoring system adapted from both the
      CONsolidated Standards of Reporting Trials (CONSORT) statement and
      recommendations for assessing trials by the Center of Evidence Based Medicine of
      Oxford. RESULTS: Twenty-two papers were selected and reviewed, with 5 studies
      performed in horses, 16 in dogs, and 1 in cats. The strength of evidence was low
      for all nutraceuticals except for omega-3 fatty acid in dogs. There were limited
      numbers of rigorous randomized controlled trials and of participants in clinical
      trials. CONCLUSIONS AND CLINICAL IMPORTANCE: The evidence of efficacy of
      nutraceuticals is poor, with the exception of diets supplemented with omega-3
      fatty acids in dogs. Greater access to systematic reviews must be part of the
      objectives of the veterinary science in the future. Their reporting would be
      improved by internationally agreed-upon criteria for standards and guidelines.

PMID- 22404507
TI  - C2 from Beet curly top virus promotes a cell environment suitable for efficient
      replication of geminiviruses, providing a novel mechanism of viral synergism.
AB  - * Geminiviruses are plant viruses with circular, single-stranded (ss) DNA genomes
      that infect a wide range of species and cause important losses in agriculture.
      Geminiviruses do not encode their own DNA polymerase, and rely on the host cell
      machinery for their replication. * Here, we identify a positive effect of the
      curtovirus Beet curly top virus (BCTV) on the begomovirus Tomato yellow leaf curl
      Sardinia virus (TYLCSV) infection in Nicotiana benthamiana plants. * Our results
      show that this positive effect is caused by the promotion of TYLCSV replication
      by BCTV C2. Transcriptomic analyses of plants expressing C2 unveil an up
      regulation of cell cycle-related genes induced on cell cycle re-entry;
      experiments with two mutated versions of C2 indicate that this function resides
      in the N-terminal part of C2, which is also sufficient to enhance geminiviral
      replication. Moreover, C2 expression promotes the replication of other
      geminiviral species, but not of RNA viruses. * We conclude that BCTV C2 has a
      novel function in the promotion of viral replication, probably by restoring the
      DNA replication competency of the infected cells and thus creating a favourable
      cell environment for viral spread. Because C2 seems to have a broad impact on the
      replication of geminiviruses, this mechanism might have important epidemiological
      implications.

PMID- 22404509
TI  - Phlebotomy or bloodletting: from tradition to evidence-based medicine.

PMID- 22404510
TI  - Good evidence begets good policy: or so it should be.

PMID- 22404513
TI  - Plasticizer detection in urine samples after autologous blood transfusion.

PMID- 22404514
TI  - Is the INR a reliable test for decreased thrombin generation?

PMID- 22404516
TI  - Patrick Loudon Mollison.

PMID- 22404517
TI  - Review article: bismuth-based therapy for Helicobacter pylori eradication in
      children.
AB  - BACKGROUND: Because of the decrease in the Helicobacter pylori eradication rate
      after standard triple therapy with a proton pump inhibitor and two antibiotics,
      bismuth-based therapy has recently been recommended as alternate first-line
      regimen in children. AIM: To comprehensively review the clinical, pharmacologic
      and microbiologic properties of bismuth salts, and to summarise the evidence for
      the therapeutic efficacy of bismuth-based therapy for H. pylori eradication in
      children. METHODS: Bibliographical searches were performed in MEDLINE. Results on
      the efficacy of bismuth-containing regimens on H. pylori eradication were
      combined using the inverse variance method. RESULTS: Bismuth monotherapy showed a
      very low efficacy. Overall, the mean eradication rate with bismuth-based dual
      therapy was 68% (95% CI, 60-76%) (intention-to-treat analysis-ITT) and 73% (95%
      CI, 64-81%) (per protocol-PP). In case series, the overall percentages of
      children with successful eradication for triple therapy containing bismuth were
      82% (95% CI, 76-88%) and 86% (95% CI, 80-92%) according to ITT and PP
      respectively. In comparative studies, H. pylori eradication rates ranged between
      69% and 85% according to ITT and between 74% and 96% PP. Side effects included
      dark stools, urine discoloration, black tongue, burning tongue, and marked
      darkness of the gums. CONCLUSIONS: The evidence in favour of bismuth compounds
      for treating infected children is still not clear. Well-designed, randomised,
      multi-centre studies of H. pylori eradication trials in children comparing
      bismuth-based triple therapy with the best available recommended first-line
      therapies are needed. The evidence obtained from audited case series that produce
      an eradication rate of >95% on PP analysis should also be considered.

PMID- 22404518
TI  - Involvement of the gamma-secretase-mediated EphA4 signaling pathway in synaptic
      pathogenesis of Alzheimer's disease.
AB  - Loss of synapses is associated with cognitive impairment in Alzheimer's disease
      (AD). However, the molecular mechanism underlying this synaptic impairment is not
      well understood. EphA4 is a substrate of gamma-secretase, and the gamma-secretase
      cleaved EphA4 intracellular domain (EICD) is known to enhance the formation of
      dendritic spines via activation of the Rac signaling pathway. Here, we show that
      the amount of Rac1 is significantly reduced, and correlated with the level of
      EICD in the frontal lobes of AD patients. Biochemical analyses revealed that the
      amount of membrane-associated EICD was decreased and strongly correlated with the
      level of membrane-associated Rac1, which is considered to be active Rac1. The
      synaptic scaffolding protein, postsynaptic density (PSD)-95, was specifically
      decreased in AD, and the amount of PSD-95 correlated with the level of Rac1.
      Moreover, the amounts of Rac1 and PSD-95 were negatively correlated with the
      extent of tau phosphorylation, which is crucial for neurofibrillary tangle
      formation. These results suggest that attenuation of the EICD-mediated Rac
      signaling pathway is involved in the synaptic pathogenesis of AD.

PMID- 22404519
TI  - How the 'HAMMER' can help in effectively treating skin cancer.

PMID- 22404520
TI  - Semisynthetic, site-specific ubiquitin modification of alpha-synuclein reveals
      differential effects on aggregation.
AB  - The process of neurodegeneration in Parkinson's Disease is intimately associated
      with the aggregation of the protein alpha-synuclein into toxic oligomers and
      fibrils. Interestingly, many of these protein aggregates are found to be post
      translationally modified by ubiquitin at several different lysine residues.
      However, the inability to generate homogeneously ubiquitin modified alpha
      synuclein at each site has prevented the understanding of the specific
      biochemical consequences. We have used protein semisynthesis to generate nine
      site-specifically ubiquitin modified alpha-synuclein derivatives and have
      demonstrated that different ubiquitination sites have differential effects on
      alpha-synuclein aggregation.

PMID- 22404521
TI  - Three-dimensional transesophageal echocardiography of a Medtronic Hall-type
      tilting disk valve.

PMID- 22404522
TI  - Pharmacokinetic study of arctigenin in rat plasma and organ tissue by RP-HPLC
      method.
AB  - A high-performance liquid chromatography (HPLC) technique was developed for the
      determination of arctigenin in plasma and various organs of rats after the oral
      administration of 30, 50 and 70 mgkg(-1) of arctigenin to the Sprague-Dawley
      rats. Results showed that the validated HPLC method was simple, fast,
      reproducible and suitable to the determination of arctigenin in rat plasma and
      organ tissue and one-compartmental model with zero-order absorption process can
      well describe the changes of arctigenin concentration in the plasma. The
      concentration of compound was highest in the spleen, less in the liver and the
      least in the lung.

PMID- 22404523
TI  - Anopheles gambiae corazonin: gene structure, expression and effect on mosquito
      heart physiology.
AB  - Haemolymph flow in mosquitoes is primarily driven by the contraction of a dorsal
      vessel that is subdivided into an abdominal heart and a thoracic aorta. The
      factors that regulate mosquito heart contractions are not understood, but in
      other insects heart physiology is partially controlled by several neurohormones.
      One of these is corazonin, a neuropeptide initially discovered because of its
      cardioacceleratory activity in the cockroach Periplaneta americana. In the
      present study, we describe the corazonin gene and transcript structure in the
      mosquito Anopheles gambiae, characterize its developmental expression, and test
      its role in modulating heart physiology. We show that the A. gambiae corazonin
      gene encodes the most common form of the corazonin peptide ([Arg(7) ]-corazonin)
      and that it is alternatively spliced, with the only difference between the
      transcripts occurring in the 5' untranslated region. Analysis of the
      developmental expression of corazonin and the corazonin receptor revealed that
      transcription of both follows a bimodal distribution, with highest mRNA levels in
      2nd instar larvae and during the pupa to adult transition. Finally, experiments
      where mosquitoes were injected with various doses of corazonin and experiments
      where the transcription of corazonin and the corazonin receptor were reduced by
      RNA interference failed to detect a significant role for this neuropeptide in
      modulating mosquito heart physiology.

PMID- 22404524
TI  - Copper-catalyzed alkylation of benzoxazoles with secondary alkyl halides.
AB  - Copper-catalyzed direct alkylation of benzoxazoles using nonactivated secondary
      alkyl halides has been developed. The best catalyst is a new copper(I) complex
      (1), and the reactions are promoted by bis[2-(N,N-dimethylamino)ethyl] ether.

PMID- 22404525
TI  - Ultrasound-guided block of the axillary nerve: a case series of potential
      clinical applications.
AB  - The specific blocking of the axillary nerve has never been investigated
      clinically. We present four cases illustrating potential applications of the
      axillary nerve block in the perioperative setting and discuss possible directions
      for future research in this area. The axillary nerve blocks were all performed
      using a newly developed in-plane ultrasound-guided technique. In one patient
      undergoing arthroscopic shoulder surgery, we used the axillary nerve block as the
      only analgesic combined with propofol sedation and spontaneous breathing. Chronic
      shoulder pain was eliminated after the axillary nerve block in two patients. The
      pain score after arthroscopic shoulder surgery in these two patients remained low
      until termination of the nerve block. In a fourth patient, severe post-operative
      pain after osteosynthesis of a displaced proximal humerus fracture was almost
      eliminated after performing an axillary nerve block. These findings warrant
      larger clinical trials that investigate the pain-mediating role of the axillary
      nerve in the perioperative setting.

PMID- 22404526
TI  - The relationship between alcohol consumption, gambling behaviour and problem
      gambling during a single visit to a gambling venue.
AB  - INTRODUCTION AND AIMS: Despite the well-documented comorbidity between disordered
      alcohol use and problem gambling, little is known about the co-occurrence of
      drinking and gambling in gambling venues. This paper appears to be the first to
      investigate the association between drinking and gambling behaviour among a large
      sample of gamblers during a specific, non-laboratory gambling episode. DESIGN AND
      METHODS: We conducted a mail survey of all available households in the Northern
      Territory of Australia, including questions on drinking and gambling behaviour on
      the last visit to a gambling venue. We estimate the effect of moderate (1-4
      standard drinks) and risky (>4 standard drinks) alcohol consumption on gambling
      participation and gambling duration for both problem and non-problem gamblers
      using regression analysis of 7044 survey responses. RESULTS: The probability of
      participating in electronic gaming machine (EGM) gambling decreased with alcohol
      consumption for non-problem gamblers, while the probability of participating in
      TAB (Totalisator Agency Board, off-course totalisator) gambling increased with
      risky alcohol consumption for all gamblers. Alcohol consumption was not
      associated with EGM gambling participation for problem gamblers. Moderate alcohol
      consumption was negatively associated with EGM gambling duration, with a stronger
      effect observed for problem gamblers. DISCUSSION AND CONCLUSIONS: Moderate
      alcohol consumption is inversely correlated with both the duration of play and
      probability of participation for EGM gambling. Current laboratory studies do not
      predict the drinking-gambling behaviour of the general population in non
      laboratory settings. Future research on alcohol and gambling co-occurrence must
      explicitly consider the drinking and gambling environment in order to produce
      policy-relevant findings.

PMID- 22404527
TI  - Use of acupuncture in the management of chronic haemophilia pain.
AB  - Persons with haemophilia experience persistent pain resulting in chronic
      arthritic symptoms. The older person with haemophilia who did not benefit from
      primary prophylaxis are particularly at risk for persistent pain in multiple
      target joints as a result of repeated joint bleeding with delayed treatment
      received. The National Pain Study, Ref. [11] identified over 700 persons with
      haemophilia who rated daily persistent pain as 4.22/10 (SD +/- 2.05) using a
      visual analogue scale. The study suggests that persons are continually seeking
      additional resources to relieve pain. This study seeks to identify: (i) effects
      of acupuncture use for persons with haemophilia who experience persistent joint
      pain as a result of repeated haemarthrosis and (ii) document no reported
      increased bleeding risk as a result of acupuncture use. End points include the
      subjects reported perception of reduction in pain via the 10-point visual
      analogue pain scale and bleeding. Nine subjects participated in the study, some
      who received a factor replacement to 15% correction and others who did not
      receive factor prior to any acupuncture sessions totaling 14 acupuncture
      treatments. No one of the subjects experienced bleeding or bruising. Six of the
      nine subjects reported an improvement in pain scores by at least 50%. Seven of
      the nine quality of life (QOL) domains within the QOL SF-36 questionnaire
      improved, suggesting a perception by subjects of improvement. This study suggests
      that acupuncture therapy can be a safe additional modality for pain management
      therapies in persons with haemophilia, although larger randomized studies are
      needed for further validation.

PMID- 22404528
TI  - Dynamics of conformational Ca2+-switches in signaling networks detected by a
      planar plasmonic device.
AB  - Ca(2+)-sensor proteins regulate a variety of intracellular processes by adopting
      specific conformations in response to finely tuned changes in Ca(2+)
      concentration. Here we present a surface plasmon resonance (SPR)-based approach,
      which allows for simultaneous detection of conformational dynamics of four Ca(2+)
      sensor proteins (calmodulin, recoverin, GCAP1, and GCAP2) operating in the
      vertebrate phototransduction cascade, over variations in Ca(2+) concentration in
      the 0.1-0.6 MUM range. By working at conditions that quantitatively mimic those
      found in the cell, we show that the method is able to detect subtle differences
      in the dynamics of each Ca(2+)-sensor, which appear to be influenced by the
      presence of free Mg(2+) at physiological concentration and by posttranslational
      modifications such as myristoylation. Comparison between the macroscopic Ca(2+)
      binding constants, directly measured by competition with a chromophoric chelator,
      and the concerted binding-conformational switch detected by SPR at equilibrium
      reveals the relative contribution of the conformational change process to the SPR
      signal. This process appears to be influenced by the presence of other cations
      that perturb Ca(2+)-binding and the conformational transition by competing with
      Ca(2+), or by pure electrostatic screening. In conclusion, the approach described
      here allows a comparative analysis of protein conformational changes occurring
      under physiologically relevant molecular crowding conditions in ultrathin
      biosensor layers.

PMID- 22404531
TI  - Suprapubic versus transurethral bladder drainage after radical prostatectomy:
      impact on patient discomfort.
AB  - We evaluated the feasibility and the benefits of total prostatectomy with
      suprapubic cystostomy drainage instead of a urethral Foley catheter. Of 65
      consecutive total retropubic prostatectomies, 42 were carried out with the
      suprapubic cystostomy, and 23 with the urethral Foley catheter. Patients were
      asked postoperatively to complete a 5-cm visual analog scale on pain intensity
      related to the catheter and to urination after catheter removal. No problem
      related to cystostomy per se was observed. In the cystostomy group, over 85% and
      69% of men perceived no urinary symptoms during catherization and no painful
      urination after catheter removal, respectively; whereas in the Foley group, 91%
      and 65% perceived those symptoms (P < 0.001 and P < 0.01, respectively). These
      findings suggest that urethral catheter-free prostatectomy is a good alternative
      to that with a urethral Foley catheter, and it gives patients an improved quality
      of early postoperative life.

PMID- 22404530
TI  - Phytochemical antioxidants modulate mammalian cellular epigenome: implications in
      health and disease.
AB  - In living systems, the mechanisms of inheritance involving gene expression are
      operated by (i) the traditional model of genetics where the deoxyribonucleic acid
      (DNA) transcription and messenger ribonucleic acid stability are influenced by
      the DNA sequences and any aberrations in the primary DNA sequences and (ii) the
      epigenetic (above genetics) model in which the gene expression is regulated by
      mechanisms other than the changes in DNA sequences. The widely studied epigenetic
      alterations include DNA methylation, covalent modification of chromatin
      structure, state of histone acetylation, and involvement of microribonucleic
      acids. SIGNIFICANCE: Currently, the role of cellular epigenome in health and
      disease is rapidly emerging. Several factors are known to modulate the epigenome
      regulated gene expression that is crucial in several pathophysiological states
      and diseases in animals and humans. Phytochemicals have occupied prominent roles
      in human diet and nutrition as protective antioxidants in prevention/protection
      against several disorders and diseases in humans. RECENT ADVANCES: However, it is
      beginning to surface that the phytochemical phenolic antioxidants such as
      polyphenols, flavonoids, and nonflavonoid phenols function as potent modulators
      of the mammalian epigenome-regulated gene expression through regulation of DNA
      methylation, histone acetylation, and histone deacetylation in experimental
      models. CRITICAL ISSUES AND FUTURE DIRECTIONS: The antioxidant or pro-oxidant
      actions and their involvement in the epigenome regulation by the phytochemical
      phenolic antioxidants should be at least established in the cellular models under
      normal and pathophysiological states. The current review discusses the mechanisms
      of modulation of the mammalian cellular epigenome by the phytochemical phenolic
      antioxidants with implications in human diseases.

PMID- 22404532
TI  - Dengue virus infection in renal allograft recipients.

PMID- 22404533
TI  - In situ X-ray diffraction study of Na+ saturated montmorillonite exposed to
      variably wet super critical CO2.
AB  - Reactions involving variably hydrated super critical CO(2) (scCO(2)) and a Na
      saturated dioctahedral smectite (Na-STX-1) were examined by in situ high-pressure
      X-ray diffraction at 50  degrees C and 90 bar, conditions that are relevant to
      long-term geologic storage of CO(2). Both hydration and dehydration reactions
      were rapid with appreciable reaction occurring in minutes and near steady state
      occurring within an hour. Hydration occurred stepwise as a function of increasing
      H(2)O in the system; 1W, 2W-3W, and >3W clay hydration states were stable from ~2
      30%, ~31-55 < 64%, and >= ~71% H(2)O saturation in scCO(2), respectively.
      Exposure of sub 1W clay to anhydrous scCO(2) caused interlayer expansion, not
      contraction as expected for dehydration, suggesting that CO(2) intercalated the
      interlayer region of the sub 1W clay, which might provide a secondary trapping
      mechanism for CO(2). In contrast, control experiments using pressurized N(2) and
      similar initial conditions as in the scCO(2) study, showed little to no change in
      the d(001) spacing, or hydration states, of the clay. A salient implication for
      cap rock integrity is that clays can dehydrate when exposed to wet scCO(2). For
      example, a clay in the ~3W hydration state could collapse by ~3 A in the c*
      direction, or ~15%, if exposed to scCO(2) at less than or equal to about 64%
      H(2)O saturation.

PMID- 22404534
TI  - Nuclear translocation of FGF8 and its implication to induce Sprouty2.
AB  - Fibroblast growth factor 8 (FGF8) functions as a local organizing signal for the
      tectum and cerebellum. FGF8 activates Ras-ERK signaling pathway to induce
      cerebellar development. We paid attention to the difference in the expression
      pattern of the molecules that are induced by FGF8 in the mid-hind brain region
      during normal development and after FGF8 misexpression; some are expressed in the
      area corresponding to the ERK activation domain but the others are expressed
      corresponding to the Fgf8 expression domain. Since some of the FGF family members
      are localized in the nucleus, we wondered if FGF8 could localize in the nuclei
      and function in the nucleus. We first show that in cultured NIH3T3 cells
      transfected FGF8b could localize in the nucleus. Transfected FGF8b could also
      localize in the nucleus of the cells in the chick neural tube. In mouse embryonic
      neural tube, we detected endogenous FGF8 in the nuclei. Implantation of an FGF8b
      soaked bead showed that exogenous FGF8b could be translocated to the nuclei in
      the isthmus. Furthermore, signal-peptide-deletion mutant of FGF8b mainly
      localized in the nuclei, and induced Sprouty2 without activating ERK in the
      mesencephalon. Signal-peptide-deletion mutant of FGF8b could not induce Pax2
      expression. Taken together, we concluded that FGF8b could be translocated to the
      nuclei, and that the nuclear FGF8 could function as transcriptional regulator to
      induce Sprouty2 in the isthmus.

PMID- 22404535
TI  - Effect of acid-suppressive therapy on narrow band imaging findings in
      gastroesophageal reflux disease: a pilot study.
AB  - Standard endoscopy is an insensitive test for gastroesophageal reflux disease
      (GERD). Narrow band imaging (NBI) endoscopy enhances visualization of the distal
      esophagus. NBI patterns like intrapapillary capillary loop (IPCL) dilatation,
      tortuosity, and increased number; microerosions; increased vascularity at the
      squamocolumnar junction (SCJ); ridge-villous pattern below the SCJ; and presence
      of columnar islands in the distal esophagus have been suggested as features of
      GERD. We evaluated the effect of proton pump inhibitor (PPI) therapy on NBI
      findings in GERD patients. Patients prospectively underwent NBI upper endoscopy
      before and after PPI therapy. NBI findings were recorded at each endoscopy.
      Twenty-one patients with GERD symptoms (mean age 60.0 years; males 90.5%; white
      90.5%) were studied. After PPI therapy, there was a significant reduction in the
      proportion of patients with the following NBI features: IPCL tortuosity (90% vs.
      4.8%, P < 0.0001), dilated IPCLs (86% vs. 9.5%, P < 0.0001), and increased
      vascularity at the SCJ (43% vs. 9.5%, P= 0.0082). PPI led to healing of all
      microerosions (71% vs. 0%, P < 0.0001) and disappearance of ridge-villous
      patterns below the SCJ (14% vs. 0%, P < 0.0001). There was no significant change
      in the proportion of patients with increased numbers of IPCLs pre- and post-PPI
      therapy (71% vs. 48%, P= 0.09) or columnar islands in the distal esophagus (38%
      vs. 29%, P= 0.31). In patients with GERD symptoms, NBI features suggestive of
      GERD respond to PPI; suggesting these features are truly acid-mediated. These
      findings need to be confirmed by randomized controlled trials.

PMID- 22404536
TI  - Autophagy machinery controls nitrogen remobilization at the whole-plant level
      under both limiting and ample nitrate conditions in Arabidopsis.
AB  - * Processes allowing the recycling of organic nitrogen and export to young leaves
      and seeds are important determinants of plant yield, especially when plants are
      nitrate-limited. Because autophagy is induced during leaf ageing and in response
      to nitrogen starvation, its role in nitrogen remobilization was suspected. It was
      recently shown that autophagy participates in the trafficking of Rubisco
      containing bodies to the vacuole. * To investigate the role of autophagy in
      nitrogen remobilization, several autophagy-defective (atg) Arabidopsis mutants
      were grown under low and high nitrate supplies and labeled with at the vegetative
      stage in order to determine (15) N partitioning in seeds at harvest. Because atg
      mutants displayed earlier and more rapid leaf senescence than wild type, we
      investigated whether their defects in nitrogen remobilization were related to
      premature leaf cell death by studying the stay-green atg5.sid2 and atg5.NahG
      mutants. * Results showed that nitrogen remobilization efficiency was
      significantly lower in all the atg mutants irrespective of biomass defects,
      harvest index reduction, leaf senescence phenotypes and nitrogen conditions. * We
      conclude that autophagy core machinery is needed for nitrogen remobilization and
      seed filling.

PMID- 22404537
TI  - Cognitive and neural correlates of aerobic fitness in obese older adults.
AB  - BacKGROUND/STUDY CONTEXT: Aerobic fitness is associated with preserved cognition
      and brain volume in older adulthood. The current study investigated whether the
      benefits of aerobic fitness extend to obese older adults, a segment of the
      population that is rapidly growing and who exhibit compromised cognition and
      brain structure relative to their nonobese counterparts. METHODS: Measures of
      obesity, aerobic fitness, cognition (processing speed, executive function,
      spatial ability, memory), and regional brain volumes (prefrontal gray, prefrontal
      white, hippocampus) were obtained from 19 obese older adults aged 65 to 75.
      Hierarchical linear regression analyses were conducted to examine the proportion
      of unique variance in cognitive and volumetric measures accounted for by aerobic
      fitness after controlling for covariates (age, gender, and waist circumference).
      RESULTS: Aerobic fitness accounted for a significant amount of unique variance in
      processing speed (adjusted R (2) = .44), executive function (adjusted R (2) =
      .34), and hippocampal volume (adjusted R (2) = .27). CONCLUSION: This novel
      pattern of results suggests that obesity does not preclude the benefits of
      fitness for cognition and brain volume in older adults. Fitness appears to be a
      beneficial factor for maintenance of processing speed, executive function, and
      hippocampal volume, which are vulnerable to age- and/or obesity-related decline.

PMID- 22404538
TI  - Age effects on emotion recognition in facial displays: from 20 to 89 years of
      age.
AB  - BACKGROUND/STUDY CONTEXT: An emotion recognition task that morphs emotional
      facial expressions from an initial neutral expression to distinct increments of
      the full emotional expression was administered to 482 individuals, 20 to 89 years
      of age. METHODS: Participants assessed six basic emotions at 25%, 50%, 75%, and
      100% of the full facial expression. RESULTS: Participants in the three oldest age
      groups (60s, 70s, and 80s) demonstrated decreased performance for the recognition
      of the fear, anger, and sad emotions. Increased age was associated with increased
      recognition rates for the disgust expression, whereas no age effect was detected
      for the happy and surprise expressions. Covariate analyses revealed age effects
      were reduced by processing speed, but were unaffected by decision-making ability.
      The effects of age on individual emotions and levels of presentation are
      discussed. CONCLUSION: These findings suggest that age has the greatest impact on
      the recognition of the sad emotion and the greatest age effect at the 50% level
      of presentation across the adult life span.

PMID- 22404539
TI  - Adult aging, processing style, and the perception of biological motion.
AB  - BACKGROUND/STUDY CONTEXT: Social perception may be influenced by the extent to
      which individuals focus on global, rather than local, detail-based, processing of
      information about others. Here the authors investigated whether global processing
      biases relate to successful detection of actions and emotions from point-light
      biological motion (BM) stimuli. Also explored is whether age differences in BM
      perception and global-local processing biases are related. METHODS: One hundred
      and twenty-seven participants (aged 18 to 86) completed tasks assessing BM
      perception and global-local processing. RESULTS: Successful decoding of actions
      and emotions from BM stimuli was correlated with global processing bias. Older
      adults performed more poorly on BM decoding and had a local processing bias.
      However, age differences in global-local processing could not fully explain
      differences in decoding actions or emotions from point-light displays.
      CONCLUSION: Therefore, although there was an association between age, perceptual
      processing bias, and detection of BM, other factors must be important in
      explaining age-related change in social perception.

PMID- 22404540
TI  - Online grammaticality judgments in French young and older adults.
AB  - BACKGROUND/STUDY CONTEXT: A goal of language and aging research is to determine
      the nature of change in language-processing skills. In this study the authors
      examine the role of age and use of cues (e.g., word order, verbal agreement,
      sentence structure) on online sentence processing. METHODS: French young and
      older adults were asked to detect grammatical violations in sentences as quickly
      as possible. Detection times were analyzed as a function of participants' age and
      sentence characteristics (i.e., violation type, span, and position). RESULTS:
      Above and beyond main effects of participant's age and linguistic features,
      results showed age-related differences in effects of linguistic cues on sentence
      processing and important individual differences during aging in hierarchies of
      cue strength. CONCLUSION: Young and older adults use similar linguistic cues in
      the online process, but loss of cognitive resources with age shows a cost of cue
      use and a greater use of context.

PMID- 22404541
TI  - A critical evaluation of the cognitive penetrability of posture.
AB  - BACKGROUND/STUDY CONTEXT: Interactions between postural control and cognitive
      activity as evidenced by dual-tasking studies are common, and especially
      pronounced in the elderly. Some authors have used this finding to suggest that
      posture is "cognitively penetrable." METHODS: The authors present a critical look
      at the "cognitive penetrability of posture" concept. The authors first trace the
      notion back to Pylyshyn ( 1980 , Behavioral and Brain Sciences, 3, 111-169) in
      the context of visual information processing. RESULTS: The authors then argue
      that dual-tasking interference effects do not prove that posture is penetrable by
      cognition. CONCLUSION: The authors conclude that it may be valid to study
      cognitive penetrability of posture, but that such an endeavor is served best by
      adopting a hierarchical model of action control.

PMID- 22404542
TI  - Event-related potentials elicited by face identity processing in elderly adults
      with cognitive impairment.
AB  - BackGROUND/STUDY CONTEXT: Patients with mild Alzheimer's disease and mild
      cognitive impairment show selective loss of knowledge regarding facial
      identification. METHODS: The authors focus on decline effects on event-related
      potentials (ERPs) P100, N170, N250, and N400, associated with the processing of
      facial identity. Different famous and unknown faces were presented in explicit
      and implicit familiarity tasks. RESULTS: Patients with cognitive impairment
      showed modulations on P100 and N170 and greater activity in prefrontal areas in
      the earlier component. In healthy elderly individuals, but not in patients,
      famous faces modulated the long-latency ERPs N250 and N400, related to the access
      and retrieval of stored facial-related information, respectively. CONCLUSION:
      ERPs have potential as markers of neurodegenerative disease such as dementia. The
      neural systems supporting facial identification may differ in normal and
      cognitively impaired older adults.

PMID- 22404543
TI  - Acute respiratory failure caused by Leptospira spp. in 5 foals.

PMID- 22404544
TI  - Bioorthogonal profiling of protein methylation using azido derivative of S
      adenosyl-L-methionine.
AB  - Protein methyltransferases (PMTs) play critical roles in multiple biological
      processes. Because PMTs often function in vivo through forming multimeric protein
      complexes, dissecting their activities in the native contexts is challenging but
      relevant. To address such a need, we envisioned a Bioorthogonal Profiling of
      Protein Methylation (BPPM) technology, in which a SAM analogue cofactor can be
      utilized by multiple rationally engineered PMTs to label substrates of the
      corresponding native PMTs. Here, 4-azidobut-2-enyl derivative of S-adenosyl-L
      methionine (Ab-SAM) was reported as a suitable BPPM cofactor. The resultant
      cofactor-enzyme pairs were implemented to label specifically the substrates of
      closely related PMTs (e.g., EuHMT1 and EuHMT2) in a complex cellular mixture. The
      BPPM approach, coupled with mass spectrometric analysis, enables the
      identification of the nonhistone targets of EuHMT1/2. Comparison of EuHMT1/2's
      methylomes indicates that the two human PMTs, although similar in terms of their
      primary sequences, can act on the distinct sets of nonhistone targets. Given the
      conserved active sites of PMTs, Ab-SAM and its use in BPPM are expected to be
      transferable to other PMTs for target identification.

PMID- 22404545
TI  - Infliximab for the treatment of psoriasis in the U.K.: 9 years' experience of
      infusion reactions at a single centre.
AB  - BACKGROUND: Infliximab is an antitumour necrosis factor-alpha chimeric monoclonal
      antibody that is an established treatment for severe chronic plaque psoriasis.
      The recommended administration of a 2-h infusion followed by 2 h of monitoring is
      practised due to the potential occurrence of infusion reactions. However,
      accelerated infusions and shortened monitoring periods are used in patients with
      rheumatological disorders and inflammatory bowel disease without an increase in
      adverse events. OBJECTIVES: To review the standard infliximab infusion protocol,
      the incidence of acute infusion reactions, the use of concomitant methotrexate
      and the clinical relevance of the 2-h postinfusion monitoring period. METHODS: A
      retrospective case note and pharmacy database review of all infliximab infusions
      administered to patients with psoriasis at a tertiary dermatology centre was
      carried out. RESULTS: Fifty-nine consecutive patients received a total of 858
      infliximab infusions (range 1-43 infusions per patient) between January 2001 and
      June 2010. The incidence of infusion reactions was 1.5%, affecting 16.9% of
      patients and occurring between the first and eleventh infusions. Mild, moderate
      and severe acute reactions occurred in 0.6% (n=5), 0.3% (n=3) and 0.3% (n=3) of
      infliximab infusions, respectively. Thirty-three patients (56%) received
      concomitant systemic treatments during part of or throughout the infliximab
      treatment, including 24 (41%) on methotrexate (5-20 mg weekly). The prevalence of
      infusion reactions in patients receiving infliximab alone was 27% compared with
      4% in those receiving concomitant methotrexate (P=0.05). All infusion reactions
      were managed as per our trust protocol with only one infusion reaction occurring
      in the postinfusion period (10 min after infusion completion). CONCLUSION: The
      risk of infusion reactions in our cohort of patients was low, with the majority
      occurring early in the treatment cycle. Concomitant methotrexate may reduce this
      risk. A shortened postinfusion monitoring period can be safely considered.

PMID- 22404546
TI  - Generation of mariner-based transposon insertion mutant library of Bacillus
      sphaericus 2297 and investigation of genes involved in sporulation and mosquito
      larvicidal crystal protein synthesis.
AB  - Bacillus sphaericus has been used with great success in mosquito control programs
      worldwide. Under conditions of nutrient limitation, it undergoes sporulation via
      a series of well defined morphological stages. However, only a small number of
      genes involved in sporulation have been identified. To identify genes associated
      with sporulation, and to understand the relationship between sporulation and
      crystal protein synthesis, a random mariner-based transposon insertion mutant
      library of B. sphaericus strain 2297 was constructed and seven sporulation
      defective mutants were selected. Sequencing of the DNA flanking of the transposon
      insertion identified several genes involved in sporulation. The morphologies of
      mutants were determined by electron microscopy and synthesis of crystal proteins
      was analyzed by SDS-PAGE and Western blot. Four mutants blocked at early stages
      of sporulation failed to produce crystal proteins and had lower larvicidal
      activity. However, the other three mutants were blocked at later stages and were
      able to form crystal proteins, and the larvicidal activity was similar to wild
      type. These results indicated that crystal protein synthesis in B. sphaericus is
      dependent on sporulation initiation.

PMID- 22404547
TI  - Inverted McConnell sign.

PMID- 22404548
TI  - Cross-coupling of aryltrimethylammonium iodides with arylzinc reagents catalyzed
      by amido pincer nickel complexes.
AB  - The cross-coupling reaction of aryltrimethylammonium iodides with aryl- or
      heteroarylzinc chlorides catalyzed by amido pincer nickel complexes was
      performed. The reaction requires low catalyst loading and displays broad
      substrate scope.

PMID- 22404550
TI  - A Bayesian method to mine spatial data sets to evaluate the vulnerability of
      human beings to catastrophic risk.
AB  - Vulnerability of human beings exposed to a catastrophic disaster is affected by
      multiple factors that include hazard intensity, environment, and individual
      characteristics. The traditional approach to vulnerability assessment, based on
      the aggregate-area method and unsupervised learning, cannot incorporate spatial
      information; thus, vulnerability can be only roughly assessed. In this article,
      we propose Bayesian network (BN) and spatial analysis techniques to mine spatial
      data sets to evaluate the vulnerability of human beings. In our approach, spatial
      analysis is leveraged to preprocess the data; for example, kernel density
      analysis (KDA) and accumulative road cost surface modeling (ARCSM) are employed
      to quantify the influence of geofeatures on vulnerability and relate such
      influence to spatial distance. The knowledge- and data-based BN provides a
      consistent platform to integrate a variety of factors, including those extracted
      by KDA and ARCSM to model vulnerability uncertainty. We also consider the model's
      uncertainty and use the Bayesian model average and Occam's Window to average the
      multiple models obtained by our approach to robust prediction of the risk and
      vulnerability. We compare our approach with other probabilistic models in the
      case study of seismic risk and conclude that our approach is a good means to
      mining spatial data sets for evaluating vulnerability.

PMID- 22404551
TI  - More of A MAN with serial nerve conduction studies?

PMID- 22404549
TI  - The international factor IX treatment network survey.

PMID- 22404554
TI  - Current information on the immunologic status of occult hepatitis B infection.
AB  - Hepatitis B is one of the most frequently occurring posttransfusion infections.
      Occult hepatitis B (OB) is a form of hepatitis B in which, despite the presence
      of hepatitis B virus (HBV) DNA in the serum and hepatocytes of a carrier,
      hepatitis B surface antigen is absent. In addition to the risk of transfusion of
      infection, OB can lead to cirrhosis, hepatic cancer, and reactivation of the
      viral duplication process in the carrier. The mechanisms responsible for
      progression of OB are yet to be clarified; however, some investigators have
      suggested that genetic and immunologic variables may play a significant role in
      the resistance of some individuals and sensitivity of other patients. This review
      addresses the current information regarding immunologic status of OB-infected
      patients.

PMID- 22404555
TI  - Drug detection dogs in Australia: more bark than bite?
AB  - INTRODUCTION AND AIMS: Canines are often used by police for drug detection and
      deterrence. However, their effectiveness has been questioned. This paper aims to
      describe the experience of regular illicit drug users when in contact with drug
      detection dogs. DESIGN AND METHODS: Regular ecstasy users (n = 2127) were
      interviewed across Australia between 2008 and 2010 as part of the Ecstasy and
      Related Drugs Reporting System. RESULTS: Over the 3 year period, there was
      increased visibility of drug detection dogs by regular ecstasy users. New South
      Wales was the jurisdiction with the most reported sightings, mainly occurring at
      festivals or live music events. Despite this police presence, however, detection
      and deterrence rates remained low. Approximately two-thirds of participants who
      had seen the drug detection dogs had drugs in their possession at the most recent
      sighting, yet less than 7% were positively identified by dogs. Further, the
      majority of participants in possession of drugs took no actions after sighting
      the dogs, whereas a small group hastily consumed the drugs. DISCUSSION AND
      CONCLUSIONS: The low proportion of reported positive notifications from the dogs
      by the participants who had drugs on them at the time of sighting questions the
      accuracy and effectiveness of this procedure. Despite the increased visibility of
      police drug detection dogs, regular ecstasy users continue to use and be in
      possession of illicit drugs in public, suggesting a limited deterrence effect.
      The hasty consumption of drugs upon sighting the dogs also raises health
      concerns.

PMID- 22404556
TI  - Novel posterior reconstruction technique during robot-assisted laparoscopic
      prostatectomy: description and comparative outcomes.
AB  - The aim of the present study was to assess the impact of a novel posterior
      reconstruction technique during robot-assisted laparoscopic prostatectomy on
      continence recovery. A total of 116 consecutive patients who received the novel
      posterior reconstruction (case group) were retrospectively compared with a cohort
      of 126 patients who did not receive posterior reconstruction (control group). The
      primary end-point was the duration of continence recovery (no pad use) after
      robot-assisted laparoscopic prostatectomy. The posterior reconstruction was
      obtained by opposing the median dorsal fibrous raphe to the posterior counterpart
      of the detrusor apron, rather than the Denonvilliers' fascia. The case group
      showed higher continence rates at all points of evaluation, which were 2 weeks
      (30.1% vs 19.8%), 1 month (58.4% vs 45.7%), 3 months (82.7% vs 70.5%) and 6
      months postoperatively (95.3% vs 86.4%) (P = 0.007). Application of the novel
      posterior reconstruction technique, age and length of membranous urethra were
      significant variables for the complete recovery of continence on multivariable
      analysis. This study shows that the application of this novel PR technique
      significantly improves the recovery of continence in patients undergoing robot
      assisted laparoscopic prostatectomy.

PMID- 22404557
TI  - Survey of injury sources for a trampoline with equipment hazards designed out.
AB  - AIM: In Australia, trampolines contribute approximately one-quarter of all
      childhood play-equipment injuries. The purpose of this study was to gather and
      evaluate injury data from a nontraditional, 'soft-edged', consumer trampoline in
      which the equipment injury sources have been designed out. METHODS: A survey was
      undertaken in Queensland and New South Wales. The manufacturer of the
      nontraditional trampoline provided the University of Technology, Sydney, with
      their Australian customer database. Injury data were gathered in a pilot study by
      phone interview, then in a full study through an email survey. Results from 3817
      respondents were compared with earlier Australian and US data from traditional
      trampolines gathered from emergency departments. RESULTS:   A significantly lower
      proportion of the injuries caused by falling off or striking the equipment was
      found for this new design when compared with traditional trampolines both in
      Australia and in the USA. The age of children being injured on trampolines in
      Australia was found to be markedly lower than in North America. CONCLUSIONS: This
      research indicates that with appropriate design the more severe injuries on
      traditional trampolines can be significantly reduced.

PMID- 22404558
TI  - Neurosurgical applications of the 2-MUm thulium laser: histological evaluation of
      meningiomas in comparison to bipolar forceps and an ultrasonic aspirator.
AB  - OBJECTIVE: The authors evaluated the histological effects of the 2-MUm thulium
      laser on meningioma tissue, comparing them to the results obtained using bipolar
      forceps and an ultrasonic aspirator. METHODS: The authors analyzed nine samples
      of intracranial meningiomas. Four slices were obtained for every sample, and one
      incision was performed on each slice. Two incisions were made with a 2-MUm
      thulium laser (one set to a 6 W and another set to a 12 W power level). One
      incision was made using a bipolar forceps and the other using an ultrasonic
      aspirator. Tissue was addressed and analyzed. Upon microscope analysis, three
      zones of laser action were identified: (A) a central crater; (B) a vaporized
      zone; and (C) a shrunken layer. These three layers were measured and compared.
      RESULTS: When addressed with the laser, all nine meningiomas presented a crater
      having an average depth of 1 mm. Three layers were clearly distinguished and
      measured: A (average depth: 0.8 mm at 6 W and 1.24 mm at 12 W); B (average depth:
      0.32 mm at 6 W and 0.72 mm at 12 W); and C (average depth: 0.39 mm at 6 W and
      0.44 mm at 12 W). On slices treated with bipolar forceps incisions, only zones B
      and C were identified. Ultrasonic aspirator incisions showed a deeper A zone
      (average depth: 2.93 mm), no B zone, and a tiny C zone (average depth: 0.16 mm).
      CONCLUSIONS: Thulium laser can be safely used for the surgical removal of
      intracranial meningiomas; beyond 2 mm under the surface of action, no tissue
      alterations were found. The lesions produced on meningiomas were characterized by
      vaporization and shrinking. When compared with bipolar forceps, the thulium laser
      offers cutting precision and vaporization of the tissue. When compared to the
      cavitron ultrasonic surgical aspirator (CUSA), the laser offers shrinking and
      coagulation of small vessels.

PMID- 22404559
TI  - Low-level laser therapy enhances the stability of orthodontic mini-implants via
      bone formation related to BMP-2 expression in a rat model.
AB  - OBJECTIVE: The aim of this study was to investigate the stimulatory effects of
      low-level laser therapy (LLLT) on the stability of mini-implants in rat tibiae.
      BACKGROUND DATA: In adolescent patients, loosening is a notable complication of
      mini-implants used to provide anchorage in orthodontic treatments. Previously,
      the stimulatory effects of LLLT on bone formation were reported; here, it was
      examined whether LLLT enhanced the stability of mini-implants via peri-implant
      bone formation. MATERIALS AND METHODS: Seventy-eight titanium mini-implants were
      placed into both tibiae of 6-week-old male rats. The mini-implants in the right
      tibia were subjected to LLLT of gallium-aluminium-arsenide laser (830 nm) once a
      day during 7 days, and the mini-implants in the left tibia served as
      nonirradiated controls. At 7 and 35 days after implantation, the stability of the
      mini-implants was investigated using the diagnostic tool (Periotest). New bone
      volume around the mini-implants was measured on days 3, 5, and 7 by in vivo
      microfocus CT. The gene expression of bone morphogenetic protein (BMP)-2 in bone
      around the mini-implants was also analyzed using real-time reverse-transcription
      polymerase chain reaction assays. The data were statistically analyzed using
      Student's t test. RESULTS: Periotest values were significantly lower (0.79- to
      0.65-fold) and the volume of newly formed bone was significantly higher (1.53
      fold) in the LLLT group. LLLT also stimulated significant BMP-2 gene expression
      in peri-implant bone (1.92-fold). CONCLUSIONS: LLLT enhanced the stability of
      mini-implants placed in rat tibiae and accelerated peri-implant bone formation by
      increasing the gene expression of BMP-2 in surrounding cells.

PMID- 22404560
TI  - Diastereoselective additions of allylmetal reagents to free and protected syn
      alpha,beta-dihydroxyketones enable efficient synthetic routes to methyl
      trioxacarcinoside A.
AB  - Two routes to the 2,6-dideoxysugar methyl trioxacarcinoside A are described. Each
      was enabled by an apparent alpha-chelation-controlled addition of an allylmetal
      reagent to a ketone substrate containing a free alpha-hydroxyl group and a beta
      hydroxyl substituent, either free or protected as the corresponding di-tert
      butylmethyl silyl ether. Both routes provide practical access to gram quantities
      of trioxacarcinose A in a form suitable for glycosidic coupling reactions.

PMID- 22404561
TI  - Dewetting of silica surfaces upon reactions with supercritical CO2 and brine:
      pore-scale studies in micromodels.
AB  - Wettability of reservoir minerals and rocks is a critical factor controlling
      CO(2) mobility, residual trapping, and safe-storage in geologic carbon
      sequestration, and currently is the factor imparting the greatest uncertainty in
      predicting capillary behavior in porous media. Very little information on
      wettability in supercritical CO(2) (scCO(2))-mineral-brine systems is available.
      We studied pore-scale wettability and wettability alteration in scCO(2)-silica
      brine systems using engineered micromodels (transparent pore networks), at 8.5
      MPa and 45  degrees C, over a wide range of NaCl concentrations up to 5.0 M.
      Dewetting of silica surfaces upon reactions with scCO(2) was observed through
      water film thinning, water droplet formation, and contact angle increases within
      single pores. The brine contact angles increased from initial values near 0
      degrees  up to 80 degrees  with larger increases under higher ionic strength
      conditions. Given the abundance of silica surfaces in reservoirs and caprocks,
      these results indicate that CO(2) induced dewetting may have important
      consequences on CO(2) sequestration including reducing capillary entry pressure,
      and altering quantities of CO(2) residual trapping, relative permeability, and
      caprock integrity.

PMID- 22404562
TI  - Microglia-like or microglia: results of the weak silver carbonate staining method
      of del Rio-Hortega.
AB  - We investigated the character and origin of the newly described "microglia-like"
      cell in the mammalian organ of Corti after aminoglycoside intoxication. We
      replicated the neomycin-induced ototoxicity model in cochleae of neonatal Sprague
      Dawley rats and used their brains as microglia positive controls. The weak silver
      carbonate staining method of del Rio-Hortega was used to identify the microglia
      like cell. The microglia-like cell was confirmed by transmission electron
      microscope (TEM). Microglia in the brain were stained while rat microglia-like
      cells in the cochlea were unstained by the weak silver carbonate staining method
      of del Rio-Hortega. Because the microglia-like cell was unstained by the method
      of del Rio-Hortega, it is unlikely that the newly found cell is related to
      microglia.

PMID- 22404563
TI  - Expression patterns of human DAB2IP protein in fetal tissues.
AB  - Human DOC-2/DAB2-interacting protein (DAB2IP) is encoded by a tumor suppressor
      gene and a newly recognized member of the Ras-GTPase-activating family. DAB2IP is
      a critical component of many signal transduction pathways mediated by Ras and
      tumor necrosis factors including apoptosis pathways, and it is involved in the
      formation of many types of tumors. DAB2IP participates in regulation of gene
      expression and pluripotency of cells. It has been reported that DAB2IP was
      expressed in different tumor tissues. Little information is available concerning
      the expression levels of DAB2IP in normal tissues and cells, however, and no
      studies of its expression patterns during the development of human embryos have
      been reported. We examined the expression of DAB2IP during human embryonic
      development to understand better DAB2IP functions. Human fetuses, weeks 9 to 38,
      and a newborn were obtained from miscarriages or stillbirths. Tissues were
      embedded in paraffin to construct arrays that were stained immunohistochemically.
      The DAB2IP-positive cells were identified and scored based on both the percentage
      of stained cells and their staining intensities. DAB2IP was expressed in most
      fetal tissues examined. DAB2IP was expressed primarily in cell cytoplasm
      throughout the fetal development. The expression levels varied among tissues and
      different gestational ages. Virtually no expression was observed in the cerebrum,
      parotid gland, thymus, thyroid gland and spleen. Expression was much greater in
      the adrenal gland and pancreas; weakly to moderately strong in the endocardium,
      stomach, kidney, testis and small intestine; and lower in liver, trachea, skin,
      ovary and endometrium. Its expression in the lung, esophagus and bladder were
      much weaker to absent.

PMID- 22404565
TI  - Moisturizing effect of alcohol-based hand rub containing okra polysaccharide.
AB  - A natural, moisturizing alcohol-based hand rub (ABHR) containing okra
      (Abelmoschus esculentus) polysaccharide was formulated to reduce the dryness
      caused by traditional hand-cleansing products. The ABHR developed also reduced
      infectious disease transmission. Preliminary evaluations of the stable natural
      hand hygiene preparations were conducted to determine preference and short-term
      moisturizing efficacy in volunteers. Formulations contained varying amounts of
      gelling agent (0.5% and 0.3% w/v). Accelerated stability testing using a
      centrifugation assay and six heating/cooling cycles of the ABHR bases were
      performed. Then, okra polysaccharide (5%, 7%, 10% and 15% w/w) was incorporated
      into the base, and stability tests were repeated. The moisturizing okra
      polysaccharide was compatible with the formulations at all concentrations. All of
      the formulated ABHRs were stable. Sensory evaluation was conducted in 36
      volunteers. The two most preferred okra ABHRs were patch-tested in 12 volunteers;
      results indicated none of the preparations caused irritation. Efficacy of the
      most preferred moisturizing ABHR containing 0.3% gelling agent and 10% (w/v) okra
      extract was determined. Short-term moisturizing efficacy of a single application
      was examined in 20 volunteers. The okra ABHR hydrated skin significantly better
      than a control ABHR (P < 0.005) at 30 min after application. Skin moisture was
      retained for 210 min of the observation period. Thus, the ABHR product containing
      moisturizing okra is safe, efficacious and possesses desirable properties. The
      formulation can be applied every 3 h for good hand hygiene with moisturizing
      efficacy.

PMID- 22404564
TI  - Vincristine modulates the expression of Ki67 and apoptosis in naturally occurring
      canine transmissible venereal tumor (TVT).
AB  - We investigated eight adult dogs that were brought to veterinary clinics with a
      history of transmissible venereal tumors (TVT). Our goal was to demonstrate the
      occurrence of apoptosis and the cessation of cell proliferation at every phase of
      scheduled chemotherapy for naturally occurring TVT. Tissue samples were collected
      immediately after weekly treatments with vincristine sulfate and processed for
      histological purposes. Sections 5 MUm thick were stained by the TUNEL reaction
      for apoptosis and immunostained for Ki67 as a proliferation marker. We observed
      that after vincristine applications, tumor cell proliferation ceased and
      apoptosis increased. Ki67 HSCORE values were significantly lowered after the
      first and second treatments with the chemotherapeutic agent compared to controls,
      whereas TUNEL HSCORE values were significantly higher after two applications of
      vincristine compared to controls. Our results suggest that scheduled vincristine
      sulfate applications stabilize the induction of tumor regression by inducing
      apoptosis and preventing cell proliferation.

PMID- 22404566
TI  - Thermal optimality of net ecosystem exchange of carbon dioxide and underlying
      mechanisms.
AB  - * It is well established that individual organisms can acclimate and adapt to
      temperature to optimize their functioning. However, thermal optimization of
      ecosystems, as an assemblage of organisms, has not been examined at broad spatial
      and temporal scales. * Here, we compiled data from 169 globally distributed sites
      of eddy covariance and quantified the temperature response functions of net
      ecosystem exchange (NEE), an ecosystem-level property, to determine whether NEE
      shows thermal optimality and to explore the underlying mechanisms. * We found
      that the temperature response of NEE followed a peak curve, with the optimum
      temperature (corresponding to the maximum magnitude of NEE) being positively
      correlated with annual mean temperature over years and across sites. Shifts of
      the optimum temperature of NEE were mostly a result of temperature acclimation of
      gross primary productivity (upward shift of optimum temperature) rather than
      changes in the temperature sensitivity of ecosystem respiration. * Ecosystem
      level thermal optimality is a newly revealed ecosystem property, presumably
      reflecting associated evolutionary adaptation of organisms within ecosystems, and
      has the potential to significantly regulate ecosystem-climate change feedbacks.
      The thermal optimality of NEE has implications for understanding fundamental
      properties of ecosystems in changing environments and benchmarking global models.

PMID- 22404568
TI  - Positional information in neural map development: lessons from the olfactory
      system.
AB  - Positional information is fundamental in development. Although molecular
      gradients are thought to represent positional information in various systems, the
      molecular logic used to interpret these gradients remains controversial. In the
      nervous system, sensory maps are formed in the brain based on gradients of axon
      guidance molecules. However, it remains unclear how axons find their targets
      based on relative, not absolute, expression levels of axon guidance receptors. No
      model solely based on axon-target interactions explains this point. Recent
      studies in the olfactory system suggested that the neural map formation requires
      axon-axon interactions, which is known as axon sorting. This review discusses how
      axon-axon and axon-target interactions interpret molecular gradients and
      determine the axonal projection sites in neural map formation.

PMID- 22404567
TI  - Improved cumulative survival in fistulas requiring surgical interventions to
      promote fistula maturation compared with endovascular interventions.
AB  - Due to high nonmaturation rates, arteriovenous fistulas (AVF) frequently require
      intervention(s) to promote maturation. Endovascular or surgical interventions are
      often undertaken to salvage nonmaturing AVFs. The objective of this study was to
      compare the impact of surgical versus endovascular interventions to promote AVF
      maturation on cumulative AVF survival. We evaluated 89 patients with new AVF
      placement from a Veterans Affairs population over a 5-year period. Of these, 46
      (52%) required intervention(s) to achieve successful maturation for dialysis: 31
      patients had surgical revisions and 15 patients had endovascular repairs. We
      compared cumulative survival between AVFs requiring no intervention, surgical
      revision, and endovascular intervention to promote AVF maturation. Cumulative
      survival was longer in AVFs receiving surgical intervention compared with
      angioplasty to promote AVF maturation (p = 0.05). One-year cumulative survival
      was 86% vs. 83% vs. 40% for no intervention vs. surgery vs. angioplasty,
      respectively. In AVFs that required interventions to promote maturation, AVFs
      with surgical intervention had longer cumulative survival compared with those
      AVFs with endovascular intervention. AVFs with surgical intervention to promote
      maturation had similar 1-year cumulative survival to those AVFs that did not
      require intervention to promote maturation.

PMID- 22404569
TI  - Determination of new immunoadjuvant saponin named QB-90, and analysis of its
      organ-specific distribution in Quillaja brasiliensis by HPLC.
AB  - An LC method was developed and validated in order to quantify the saponin
      purified fraction named QB-90 obtained from the aqueous extracts of Quillaja
      brasiliensis leaves. Previously, QB-90 was shown to be active as adjuvant in an
      experimental vaccine for herpesvirus bovine type 1 in mice. The analysis was
      performed using an RP-8 column with acetonitrile:water isocratic elution at 214
      nm. The standard curve for QB-90 was linear over the range of 0.8-10 ug mL(-1) (r
      = 0.9996). The aqueous extract showed linear response in the range of 50-1000 ug
      mL(-1) (r = 0.9996). The proposed method showed adequate repeatability and
      intermediary precision. The limits of detection (LOD) and quantification (LOQ)
      were 0.074 and 0.248 ug mL(-1), respectively. This method was applied
      successfully to analyse QB-90 organ-specific distribution in field stands of Q.
      brasiliensis and in laboratory-grown seedlings. Leaves from young plants
      accumulated higher QB-90 amounts than leaves from adult trees.

PMID- 22404570
TI  - Nosocomial transmission of NDM-1-producing Escherichia coli within a non-endemic
      area in France.
AB  - Two patients with no travel history and sharing the same room were colonized by
      the same strain of New Delhi metallo-beta-lactamase 1 (NDM-1)-producing
      Escherichia coli within a geographical area not endemic for this highly multidrug
      resistant bacterium. It was documented an absence of an epidemiological and
      bacteriological link with a third patient returning from India after surgery and
      found to be infected by an NDM-1-producing Citrobacter strain during the same
      period. Despite extensive investigation, the source of contamination of the two
      former patients was not elucidated. This case report illustrates the need of
      investigating rapidly the emergence of highly multidrug-resistant
      Enterobacteriaceae, to stop their dissemination in a nosocomial setting.

PMID- 22404572
TI  - Protective effect of hesperidin, a citrus flavanoglycone, against gamma-radiation
      induced tissue damage in Sprague-Dawley rats.
AB  - The present study was designed to evaluate the radioprotective effect of
      hesperidin, a citrus flavanoglycone, against gamma-radiation-induced cellular
      damage in the liver, heart, and kidney of rats. Whole-body gamma-radiation
      exposure (5 Gy) of healthy adult rats resulted in cellular damage and oxidative
      stress manifested as increased levels of serum marker enzymes, lipid
      peroxidation, and fibrosis in the tissues, accompanied by depletion of cellular
      glutathione and abnormal alteration in the levels of lysosomal enzymes. Treatment
      with hesperidin (50 and 100 mg/kg, p.o.) for 7 days was found to offer
      significant protection against gamma-radiation-induced toxicity in the tissues,
      which was evident by the improved status of most of the parameters investigated.
      Further, the histological examination of periodic acid-Schiff-stained tissue
      sections of animals treated with hesperidin following radiation exposure showed
      minimal necrotic damage with a recovery pattern in a dose-dependent manner
      compared with radiation-exposed animals. The results of our study show that
      administration of hesperidin offers effective protection against gamma-radiation
      induced cellular damage and oxidative stress in rats.

PMID- 22404573
TI  - Detection of genotoxic, cytotoxic, and protective activities of Eugenia
      dysenterica DC. (Myrtaceae) in mice.
AB  - Eugenia dysenterica DC. (Myrtaceae), popularly known in Brazil as cagaiteira, is
      a widespread plant species in the Brazilian Cerrado. In folk medicine, the leaves
      of this plant are used to treat diarrhea and dysentery. The fruits are used for
      fresh consumption and industrial purposes. Because of the use of this plant as a
      therapeutic resource and food, the present study evaluated the genotoxic,
      cytotoxic, antigenotoxic, and anticytotoxic effects of the lyophilized ethanolic
      leaf extract of E. dysenterica using the mouse bone marrow micronucleus test. The
      genotoxicity and antigenotoxicity of this extract were evaluated using the
      frequency of micronucleated polychromatic erythrocytes, and the cytotoxicity and
      anticytotoxicity were assessed by the polychromatic and normochromatic
      erythrocyte ratio. According to our results, the lyophilized ethanolic leaf
      extract of E. dysenterica exhibited genotoxic and cytotoxic effects at the higher
      doses and protection against cyclophosphamide-induced genotoxic and cytotoxic
      actions at all doses tested.

PMID- 22404574
TI  - Chemopreventive effects of cardamom (Elettaria cardamomum L.) on chemically
      induced skin carcinogenesis in Swiss albino mice.
AB  - The chemopreventive potential of cardamom was evaluated on 7,12
      dimethylbenz[a]anthracene-initiated and croton oil-promoted mouse skin
      papillomagenesis. A significant reduction in the values of tumor incidence, tumor
      burden, and tumor yield and the cumulative number of papillomas was observed in
      mice treated orally with 0.5 mg of cardamom powder in suspension continuously at
      pre-, peri-, and post-initiational stages of papillomagenesis compared with the
      control group. The average weight and diameter of tumors recorded were also
      comparatively lower in the cardamom-treated mouse group. Treatment of cardamom
      suspension by oral gavage for 15 days resulted in a significant decrease in the
      lipid peroxidation level of the liver (P < .01). In addition, the reduced
      glutathione level was significantly elevated in comparison with the control group
      (P < .05) following cardamom suspension treatment. Taken together, these findings
      indicate the potential of cardamom as a chemopreventive agent against two-stage
      skin cancer.

PMID- 22404576
TI  - Asphalt fume exposure levels in North American asphalt production and roofing
      manufacturing operations.
AB  - This study extends by 8 years (1998-2005) a previous survey of asphalt fume
      exposures within North American asphalt processing and roofing product
      manufacturing workers. It focuses on characterizing personal, full-shift samples
      and seeks to address several limitations of the previous survey. Five major
      roofing manufacturers with established occupational health programs submitted
      workplace asphalt fume sampling results to a central repository for review and
      analysis. A certified industrial hygienist-led quality assurance team oversaw the
      data collection, consolidation, and analysis efforts. The analysis dataset
      consisted of 1261 personal exposure samples analyzed for total particulate (TP)
      and benzene soluble fraction (BSF) using existing NIOSH methods. For BSF, the
      survey's arithmetic (0.25 mg/m(3), SD = 0.62) and geometric (0.12 mg/m(3), GSD =
      2.88) means indicate that the industry has sustained the control levels achieved
      in the late 1980s, early 1990s. Similar results were found for TP. The survey
      wide summary statistics are consistent with other post-1990 multi-company
      exposure studies. Although these findings indicate that currently available
      controls are capable of achieving substantial (95%) compliance with the current
      threshold limit value in asphalt processing and inorganic shingle and roll
      plants, they also show that the majority of plants are not achieving this level
      of exposure control, and that exposures are significantly higher in plants making
      other product lines, particularly organic felt products. The current
      retrospective survey of existing company exposure data, like its predecessor, has
      several important limitations. These include lack of data on smaller
      manufacturers and on several commercially important product lines; insufficient
      information on the prevalence and effectiveness of engineering controls; no
      standard criteria by which to define and assess exposures in non-routine
      operations; and a paucity of exposure data collected as part of a random sampling
      strategy. To improve efforts to characterize exposures and potential health risks
      in roofing plants, a prospective program is currently being developed and piloted
      with the aim of building a more complete, higher-quality database based on a
      common industrial hygiene protocol.

PMID- 22404575
TI  - Protective effect of sodium ferulate on acetaldehyde-treated precision-cut rat
      liver slices.
AB  - Activated hepatic stellate cells (HSCs) play a key role in hepatic fibrogenesis,
      and inhibition of HSC activation may prevent liver fibrosis. Acetaldehyde, the
      most deleterious metabolite of alcohol, triggers HSC activation in alcoholic
      liver injury. In the present study, we investigated the protective effect of
      sodium ferulate (SF), a sodium salt of ferulic acid that is rich in fruits and
      vegetables, on acetaldehyde-stimulated HSC activation using precision-cut liver
      slices (PCLSs). Rat PCLSs were co-incubated with 350 MUM acetaldehyde and
      different concentrations of SF. Hepatotoxicity was assessed by measuring enzyme
      leakage and malondialdehyde content in tissue. alpha-Smooth muscle actin,
      transforming growth factor-beta(1), and hydroxyproline were determined to assess
      the activation of HSCs. In addition, matrix metalloproteinase (MMP)-1 and the
      tissue inhibitor of metalloproteinase (TIMP-1) were determined to evaluate
      collagen degradation. SF prominently prevented the enzyme leakage in acetaldehyde
      treated slices and also inhibited HSC activation and collagen production
      stimulated by acetaldehyde. In addition, SF increased MMP-1 expression and
      decreased TIMP-1 expression. These results showed that SF protected PCLSs from
      acetaldehyde-stimulated HSC activation and liver injury, which may be associated
      with the attenuation of oxidative injury and acceleration of collagen
      degradation.

PMID- 22404577
TI  - Whole genome shotgun sequencing of one Colombian clinical isolate of
      Mycobacterium tuberculosis reveals DosR regulon gene deletions.
AB  - Several genomes of different Mycobacterium tuberculosis isolates have been
      completely sequenced around the world. The genomic information obtained have
      shown higher diversity than originally thought and specific adaptations to
      different human populations. Within this work, we sequenced the genome of one
      Colombian M. tuberculosis virulent isolate. Genomic comparison against the
      reference genome of H37Rv and other strains showed multiple deletion and
      insertions that ranged between a few bases to thousands. Excluding PPE and PG
      PGRS genes, 430 proteins present changes in at least 1 amino acid. Also, novel
      positions of the IS6110 mobile element were identified. This isolate is also
      characterized by a large genomic deletion of 3.6 kb, leading to the loss and
      modification of the dosR regulon genes, Rv1996 and Rv1997. To our knowledge, this
      is the first report of the genome sequence of a Latin American M. tuberculosis
      clinical isolate.

PMID- 22404578
TI  - Dermoscopy of lentigo maligna melanoma: report of 125 cases.
AB  - BACKGROUND: Lentigo maligna melanoma (LMM) is the most common subtype of melanoma
      on the face. Its presentation may be quite subtle, particularly in early stages,
      and delayed diagnosis is common. Few dermoscopic studies have been performed and
      the main dermoscopic features of LMM were defined by Stolz and coworkers in 2000.
      OBJECTIVES: To investigate classical as well as new dermoscopic features in a
      large series of LMM in a white-skinned population, in order to evaluate their
      diagnostic value. METHODS: One hundred and twenty-five consecutive histopathology
      proven LMMs were analysed retrospectively based on medical records, clinical and
      dermoscopic photographs by three independent observers for the presence of 19
      predefined criteria. RESULTS: At least one of the classical Stolz criteria was
      present in 87% of cases (hyperpigmented follicular opening, annular-granular
      pattern, pigmented rhomboidal structures, obliterated hair follicles). Three
      original criteria were also present at a relatively high frequency: increased
      density of the vascular network (58%), red rhomboidal structures (40%), target
      like patterns (41%). Darkening at dermoscopic examination (when compared with
      naked-eye examination) was observed in 25% of lesions. Classical dermoscopic
      features of extrafacial melanoma (atypical pigment network, irregularly
      distributed globules, dots, streaks and pseudopods) and vertical growth phase
      associated dermoscopic criteria (ulceration, blue papular areas and black
      structureless areas) were rarely seen. A large number of colours, pigmented
      rhomboidal structures, obliterated hair follicles and red rhomboidal structures
      were significantly more frequent in invasive LMMs. In contrast, in situ melanomas
      were more often associated with one or two colours and few distinctive
      dermoscopic features. CONCLUSIONS: We present herein, in a large series of LMM,
      confirmation of the diagnostic value of the classical Stolz dermoscopic criteria
      and describe four additional original criteria, mainly vascular. A correlation
      between the presence of some dermoscopic features and thicker tumoral invasion
      has also been demonstrated.

PMID- 22404579
TI  - Bilinear temperature gradient focusing in a hybrid PDMS/glass microfluidic chip
      integrated with planar heaters for generating temperature gradients.
AB  - Temperature gradient focusing (TGF) is a counterflow gradient focusing technique,
      which utilizes a temperature gradient across a microchannel or capillary to
      separate analytes. With an appropriate buffer, the temperature gradient creates a
      gradient in both the electric field and electrophoretic velocity. Combined with a
      bulk counter flow, ionic species concentrate at a unique point where the total
      velocity sums to zero and separate from each other. Scanning TGF uses varying
      bulk flow so that a large number of analytes that have large differences in
      electrophoretic mobility can be sequentially focused and passed by a single
      detection point. Up to now, scanning TGF examples have been performed using a
      linear temperature gradient which has limitations in improving peak capacity and
      resolution at the same time. In this work, we develop a bilinear temperature
      gradient along the separation channel that improves both peak capacity and
      separation resolution simultaneously. The temperature profile along the channel
      consists of a very sharp gradient used to preconcentrate the sample followed by a
      shallow gradient that increases separation resolution. A specialized design is
      developed for the heaters to achieve the bilinear profile using both analytical
      and numerical modeling. The heaters are integrated onto a hybrid PDMS/glass chip
      fabricated using conventional sputtering and soft-lithography techniques.
      Separation performance is characterized by separating several different dyes and
      amino acids that have close electrophoretic mobilities. Experiments show a
      dramatic improvement in peak capacity and resolution in comparison to the
      standard linear temperature gradient.

PMID- 22404580
TI  - Regioselective reduction of 3-substituted N-acylpyrazinium salts toward the
      synthesis of 1,2-dihydropyrazines.
AB  - The regioselective reduction of 3-substituted N-acylpyrazinium salts with n
      Bu(3)SnH has been developed for the synthesis of 3-substituted 1,2
      dihydropyrazines in yields of 56-94%. Substitution of the pyrazinium salts with
      electron-donating groups favors the formation of the 1,2-isomers as a result of
      their better stability over the 1,6-isomers. Under mild acidic conditions, 3
      methoxy substituted 1,2-dihydropyrazine was easily hydrolyzed in excellent yield
      to Delta(5)-2-oxopiperazine.

PMID- 22404581
TI  - Postural adjustment after an unexpected perturbation in children with
      haemophilia.
AB  - Children with haemophilia often bleed inside joints and muscles, which may impair
      postural adjustments. These postural adjustments are necessary to control
      postural balance during daily activities. The inability to quickly recover
      postural balance could elevate the risk of bleeding. To determine whether
      children with haemophilia have impaired postural adjustment after an unexpected
      perturbation compared with healthy children. Twenty children with haemophilia
      comprised the haemophilic group (HG), and 20 healthy, age-paired children
      comprised the control group (CG). Subjects stood on a force plate, and 4% of the
      subjects' body weight was applied via a pulley system to a belt around the
      subjects' trunks. The centre of pressure (COP) displacement was measured after
      the weight was unexpectedly released to produce a controlled postural
      perturbation followed by postural adjustment to recover balance. The subjects'
      postural adjustments in eight subsequent intervals of 1 s (t1-t8), beginning with
      the moment of weight removal, were compared among intervals and between groups.
      The applied perturbation magnitudes were the same for both groups, and no
      difference was observed between the groups in t1. However, the COP displacement
      in t2 in the HG was significantly higher than in the CG. No differences were
      observed between the groups in the other intervals. Within-group analysis showed
      that the COP was higher in t2 than in t4 (P = 0.016), t5 (P = 0.001) and t8 (P =
      0.050) in the HG. No differences were observed among intervals in the CG.
      Children with haemophilia demonstrated differences in postural adjustment while
      undergoing unexpected balance perturbations when compared with healthily
      children.

PMID- 22404582
TI  - Dynamics and genotypic composition of Emiliania huxleyi and their co-occurring
      viruses during a coccolithophore bloom in the North Sea.
AB  - We studied the temporal succession of vertical profiles of Emiliania huxleyi and
      their specific viruses (EhVs) during the progression of a natural phytoplankton
      bloom in the North Sea in June 1999. Genotypic richness was assessed by
      exploiting the variations in a gene encoding a protein with calcium-binding
      motifs (GPA) for E. huxleyi and in the viral major capsid protein gene for EhVs.
      Using denaturing gradient gel electrophoresis and sequencing analysis, we showed
      at least three different E. huxleyi and EhV genotypic profiles during the period
      of study, revealing a complex, and changing assemblage at the molecular level.
      Our results also indicate that the dynamics of EhV genotypes reflect fluctuations
      in abundance of potential E. huxleyi host cells. The presence and concentration
      of specific EhVs in the area prior to the bloom, or EhVs transported into the
      area by different water masses, are significant factors affecting the structure
      and intraspecific succession of E. huxleyi during the phytoplankton bloom.

PMID- 22404583
TI  - Dipolar recoupling in magic angle spinning solid-state nuclear magnetic
      resonance.
AB  - Solid-state nuclear magnetic resonance (SSNMR) magic angle spinning (MAS) can be
      used to record high-resolution data dominated by site-specific information.
      Although MAS introduces high resolution by attenuating the anisotropic
      broadening, it also suppresses the nuclear dipole-dipole distance information
      that is the source of most structural data in the spectra. Such information can
      be reintroduced coherently and thus selectively by the application of a carefully
      chosen sequence of radiofrequency pulses, an approach that was introduced 20
      years ago and is referred to as dipolar recoupling. This review presents the
      establishment of recoupling techniques in SSNMR and recalls the major steps
      achieved by the community throughout the last two decades. This review also
      presents emerging techniques and their corresponding new concepts. Finally, we
      present some recent developments based on second-order recoupling mechanisms and
      discuss their implications regarding dipolar truncation and the possibility to
      extract structural constraints in uniformly labeled systems.

PMID- 22404584
TI  - Free-electron lasers: new avenues in molecular physics and photochemistry.
AB  - Free-electron lasers are fourth-generation light sources that deliver extremely
      intense (>10(12) photons per pulse), ultrashort (~10(-14) s = 10 fs) light pulses
      at up to kilohertz repetition rates with unprecedented coherence properties and
      span a broad wavelength regime from soft (~10 eV) to hard X-ray energies (~15
      keV). They thus enable a whole suite of novel experiments in molecular physics
      and chemistry: Inspecting radiation-induced reactions in cold molecular ions
      provides unprecedented insight into the photochemistry of interstellar clouds and
      upper planetary atmospheres; double core-hole photoelectron spectroscopy offers
      enhanced sensitivity for chemical analysis; the dynamics of highly excited
      molecular states, pumped by vacuum ultraviolet pulses, can be inspected; and
      vacuum ultraviolet or X-ray probe pulses generally hold the promise to trace
      chemical reactions along an entire reaction coordinate with atomic spatial and
      temporal resolution. This review intends to provide a first overview on upcoming
      possibilities, emerging technologies, pioneering results, and future perspectives
      in this exciting field.

PMID- 22404585
TI  - Relativistic effects in chemistry: more common than you thought.
AB  - Relativistic effects can strongly influence the chemical and physical properties
      of heavy elements and their compounds. This influence has been noted in inorganic
      chemistry textbooks for a couple of decades. This review provides both
      traditional and new examples of these effects, including the special properties
      of gold, lead-acid and mercury batteries, the shapes of gold and thallium
      clusters, heavy-atom shifts in NMR, topological insulators, and certain specific
      heats.

PMID- 22404586
TI  - Ultrathin oxide films on metal supports: structure-reactivity relations.
AB  - Well-ordered, thin oxide films have drawn some attention in recent years as
      suitable oxide supports for modeling highly dispersed metal catalysts at the
      atomic scale. It turned out, however, that ultrathin oxide films may exhibit
      interesting catalytic properties in their own right. In this review, we discuss
      phenomena specifically connected to ultrathin oxide films to explain and
      understand the physicochemical basis of their reactivity in oxidation reactions.
      Two sets of systems are discussed, i.e., transition metal oxide films grown on
      metal substrates and native oxide films formed upon oxidation of metal surfaces.

PMID- 22404587
TI  - Photochemical and photoelectrochemical reduction of CO2.
AB  - The recent literature on photochemical and photoelectrochemical reductions of
      CO(2) is reviewed. The different methods of achieving light absorption, electron
      hole separation, and electrochemical reduction of CO(2) are considered. Energy
      gap matching for reduction of CO(2) to different products, including CO, formic
      acid, and methanol, is used to identify the most promising systems. Different
      approaches to lowering overpotentials and achieving high chemical selectivities
      by employing catalysts are described and compared.

PMID- 22404589
TI  - Live-cell super-resolution imaging with synthetic fluorophores.
AB  - Super-resolution imaging methods now can provide spatial resolution that is well
      below the diffraction limit approaching virtually molecular resolution. They can
      be applied to biological samples and provide new and exciting views on the
      structural organization of cells and the dynamics of biomolecular assemblies on
      wide timescales. These revolutionary developments come with novel requirements
      for fluorescent probes, labeling techniques, and data interpretation strategies.
      Synthetic fluorophores have a small size, are available in many colors spanning
      the whole spectrum, and can easily be chemically modified and used for
      stoichiometric labeling of proteins in live cells. Because of their brightness,
      their photostability, and their ability to be operated as photoswitchable
      fluorophores even in living cells under physiological conditions, synthetic
      fluorophores have the potential to substantially accelerate the broad application
      of live-cell super-resolution imaging methods.

PMID- 22404590
TI  - Neurotrophin signaling via long-distance axonal transport.
AB  - Neurotrophins are a family of target-derived growth factors that support
      survival, development, and maintenance of innervating neurons. Owing to the
      unique architecture of neurons, neurotrophins that act locally on the axonal
      terminals must convey their signals across the entire axon for subsequent
      regulation of gene transcription in the cell nucleus. This long-distance
      retrograde signaling, a motor-driven process that can take hours or days, has
      been a subject of intense interest. In the last decade, live-cell imaging with
      high sensitivity has significantly increased our capability to track the
      transport of neurotrophins, their receptors, and subsequent signals in real time.
      This review summarizes recent research progress in understanding neurotrophin
      receptor interactions at the axonal terminal and their transport dynamics along
      the axon. We emphasize high-resolution studies at the single-molecule level and
      also discuss recent technical advances in the field.

PMID- 22404588
TI  - Photophysics of fluorescent probes for single-molecule biophysics and super
      resolution imaging.
AB  - Single-molecule fluorescence spectroscopy and super-resolution microscopy are
      important elements of the ongoing technical revolution to reveal biochemical and
      cellular processes in unprecedented clarity and precision. Demands placed on the
      photophysical properties of the fluorophores are stringent and drive the choice
      of appropriate probes. Such fluorophores are not simple light bulbs of a certain
      color and brightness but instead have their own "personalities" regarding
      spectroscopic parameters, redox properties, size, water solubility,
      photostability, and several other factors. Here, we review the photophysics of
      fluorescent probes, both organic fluorophores and fluorescent proteins, used in
      applications such as particle tracking, single-molecule FRET, stoichiometry
      determination, and super-resolution imaging. Of particular interest is the thiol
      induced blinking of Cy5, a curse for single-molecule biophysical studies that was
      later overcome using Trolox through a reducing/oxidizing system but a boon for
      super-resolution imaging owing to the controllable photoswitching. Understanding
      photophysics is critical in the design and interpretation of single-molecule
      experiments.

PMID- 22404591
TI  - Chemistry and composition of atmospheric aerosol particles.
AB  - For more than two decades a cadre of physical chemists has focused on
      understanding the formation processes, chemical composition, and chemical
      kinetics of atmospheric aerosol particles and droplets with diameters ranging
      from a few nanometers to ~10,000 nm. They have adapted or invented a range of
      fundamental experimental and theoretical tools to investigate the
      thermochemistry, mass transport, and chemical kinetics of processes occurring at
      nanoscale gas-liquid and gas-solid interfaces for a wide range of nonideal, real
      world substances. State-of-the-art laboratory methods devised to study molecular
      spectroscopy, chemical kinetics, and molecular dynamics also have been
      incorporated into field measurement instruments that are deployed routinely on
      research aircraft, ships, and mobile laboratories as well as at field sites from
      megacities to the most remote jungle, desert, and polar locations. These
      instruments can now provide real-time, size-resolved aerosol particle physical
      property and chemical composition data anywhere in Earth's troposphere and lower
      stratosphere.

PMID- 22404592
TI  - DEER distance measurements on proteins.
AB  - Distance distributions between paramagnetic centers in the range of 1.8 to 6 nm
      in membrane proteins and up to 10 nm in deuterated soluble proteins can be
      measured by the DEER technique. The number of paramagnetic centers and their
      relative orientation can be characterized. DEER does not require crystallization
      and is not limited with respect to the size of the protein or protein complex.
      Diamagnetic proteins are accessible by site-directed spin labeling. To
      characterize structure or structural changes, experimental protocols were
      optimized and techniques for artifact suppression were introduced. Data analysis
      programs were developed, and it was realized that interpretation of the distance
      distributions must take into account the conformational distribution of spin
      labels. First methods have appeared for deriving structural models from a small
      number of distance constraints. The present scope and limitations of the
      technique are illustrated.

PMID- 22404593
TI  - Progress in modeling of ion effects at the vapor/water interface.
AB  - The behavior of halide salts at the vapor/water interface has been the focus of a
      tremendous amount of work in the past ten years. A molecular view of the
      interface has been introduced with the observation that large anions have some
      affinity for the interface, but a quantitative description of the driving forces
      that determine ion adsorption or repulsion at the interface is still missing.
      This review discusses recent developments that are based on classical and quantum
      chemical molecular simulations as well as developments that are based on simple
      potential models.

PMID- 22404594
TI  - Attosecond science: recent highlights and future trends.
AB  - We review the first ten years of attosecond science with a selection of recent
      highlights and trends and give an outlook on future directions. After introducing
      the main spectroscopic tools, we give recent examples of representative
      experiments employing them. Some of the most fundamental processes in nature have
      been studied with some results initiating controversial discussions. Experiments
      on the dynamics of single-photon ionization illustrate the importance of subtle
      effects on such extreme timescales and lead us to question some of the well
      established assumptions in this field. Attosecond transient absorption, as the
      first all-optical approach to resolve attosecond dynamics, has been used to study
      electron wave packet interferences in helium. The attoclock, a recent method
      providing attosecond time resolution without the explicit need for attosecond
      pulses, has been used to investigate electron tunneling dynamics and geometry.
      Pushing the frontiers in attosecond quantum mechanics with increasing temporal
      and spatial resolution and often limited theoretical models results in unexpected
      observations. At the same time, attosecond science continues to expand into more
      complex solid-state and molecular systems, where it starts to have impact beyond
      its traditional grounds.

PMID- 22404595
TI  - Orthogonal Intermolecular Interactions of CO molecules on a one-dimensional
      substrate.
AB  - By low-temperature scanning tunneling microscopy, we study CO molecule
      chemisorption on a quasi-one-dimensional Cu(110)-(2*1)-O surface. Atom-resolved
      images reveal how the interaction of CO with the surface Cu-O- chains gives rise
      to orthogonal attractive and repulsive intermolecular interactions. First
      principles calculations show that CO molecules induce unprecedented lifting of
      the host Cu atoms by 1 A from the Cu-O- chains, enabling the Cu-CO unit to tilt
      by 45 degrees  from the surface normal. Contrary to the behavior of CO on metal
      surfaces, this structural distortion enables unprecedented, orthogonal, short
      range intermolecular dipole-dipole attraction and long-range, surface-mediated
      repulsion. These interactions lead to self-assembly into molecular nanograting
      structures consisting of arrays of single-molecule-wide CO rows. The origin of
      the novel behavior of CO molecules in the electronic and geometrical properties
      of the quasi-one-dimensional substrate suggests that similar molecule-molecule
      and molecule-substrate interactions could play an important role at catalytic
      sites on reactive surfaces.

PMID- 22404596
TI  - Chemical synthesis of homogeneous human glycosyl-interferon-beta that exhibits
      potent antitumor activity in vivo.
AB  - Chemical synthesis of homogeneous human glycoproteins exhibiting bioactivity in
      vivo has been a challenging task. In an effort to overcome this long-standing
      problem, we selected interferon-beta and examined its synthesis. The 166 residue
      polypeptide chain of interferon-beta was prepared by covalent condensation of two
      synthetic peptide segments and a glycosylated synthetic peptide bearing a complex
      type glycan of biological origin. The peptides were covalently condensed by
      native chemical ligation. Selective desulfurization followed by deprotection of
      the two Cys(Acm) residues gave the target full-length polypeptide chain of
      interferon-beta bearing either a complex-type sialyl biantennary oligosaccharide
      or its asialo form. Subsequent folding with concomitant formation of the native
      disulfide bond afforded correctly folded homogeneous glycosyl-interferon-beta.
      The chemically synthesized sialyl interferon-beta exhibited potent antitumor
      activity in vivo.

PMID- 22404597
TI  - Panmixia supports divergence with gene flow in Darwin's small ground finch,
      Geospiza fuliginosa, on Santa Cruz, Galapagos Islands.
AB  - The divergence-with-gene-flow model of speciation has a strong theoretical basis
      with a growing number of plausible examples in nature, but remains hotly debated.
      Darwin's finches of the Galapagos Archipelago have played an important role in
      our understanding of speciation processes. Recent studies suggest that this group
      may also provide insights into speciation via divergence with gene flow. On the
      island of Santa Cruz, recent studies found evidence for adaptive divergence in
      Darwin's small ground finch, Geospiza fuliginosa, between ecologically
      contrasting arid and humid zones. Despite the short geographical distance between
      these zones, strong disruptive selection during low rainfall periods is expected
      to generate and maintain adaptive divergence. Conversely, during high rainfall
      periods, when disruptive selection is predicted to be weakened, population
      divergence in adaptive traits is expected to break down. Because periods of low
      and high rainfall irregularly alternate, the geographical pattern of adaptive
      divergence can be assumed to break down and, importantly, regenerate in situ.
      Here, we use microsatellite allele frequency data to assess the genetic
      population structure of G. fuliginosa on Santa Cruz. We sample 21 sites and four
      ecological zones across the island. We reject hypotheses of population
      substructure linked to ecological and geographical differences among sites in
      favour of a single panmictic population. Panmixia implies high levels of gene
      flow within Santa Cruz, which favours selection over genetic drift as a valid
      process generating phenotypic divergence in G. fuliginosa on Santa Cruz. We
      discuss how our findings may support classic adaptation, phenotypic plasticity,
      matching habitat choice or any combination of these three processes.

PMID- 22404598
TI  - Role of induced negative and positive emotions in sensitivity to itch and pain in
      women.
AB  - BACKGROUND: Itch and pain are common symptoms in skin disease. It has been
      suggested that negative emotions may play a role in itch and pain. To date,
      however, the role of emotions has only been studied for pain in experimental
      studies, not yet for itch. OBJECTIVES: To investigate the effects of negative and
      positive emotions on the sensitivity to itch and pain. METHODS: Film fragments
      were used to induce a negative or positive emotional state in healthy women. Itch
      and pain were induced using the following somatosensory stimuli: electrical
      stimulation, histamine iontophoresis and the cold pressor test. RESULTS: Results
      showed that the scores for itch and pain evoked by histamine and the cold pressor
      test, respectively, were significantly higher in the negative than in the
      positive emotion condition, whereas tolerance thresholds to electrical
      stimulation and the cold pressor test, and stimulus unpleasantness scores did not
      differ between the two conditions. CONCLUSIONS: These findings for the first time
      indicate in an experimental design that emotions play a role in sensitivity to
      somatosensory sensations of both itch and pain.

PMID- 22404599
TI  - Acquisition of hydrogenosomal presequences: examples from Trichomonas vaginalis.
AB  - Presequences play an important role in protein import into mitochondria-like
      organelles. Acquisition pathways have been revealed for some mitochondrial
      presequences, but little is known about hydrogenosomal presequences. Here we
      investigated the hydrogenosomal proteins of Trichomonas vaginalis and suggest
      that several hydrogenosomal presequences probably evolved from pre-existing
      sequences that were thereafter modified.

PMID- 22404600
TI  - High temperature- and high pressure-processed garlic improves lipid profiles in
      rats fed high cholesterol diets.
AB  - Garlic protects against degenerative diseases such as hyperlipidemia and
      cardiovascular diseases. However, raw garlic has a strong pungency, which is
      unpleasant. In this study, we examined the effect of high temperature/high
      pressure-processed garlic on plasma lipid profiles in rats. Sprague-Dawley rats
      were fed a normal control diet, a high cholesterol (0.5% cholesterol) diet (HCD)
      only, or a high cholesterol diet supplemented with 0.5% high temperature/high
      pressure-processed garlic (HCP) or raw garlic (HCR) for 10 weeks. The body
      weights of the rats fed the garlic-supplemented diets decreased, mostly because
      of reduced fat pad weights. Plasma levels of total cholesterol (TC), low-density
      lipoprotein cholesterol, and triglyceride (TG) in the HCP and HCR groups
      decreased significantly compared with those in the HCD group. Additionally, fecal
      TC and TG increased significantly in the HCP and HCR groups. It is notable that
      no significant differences in plasma or fecal lipid profiles were observed
      between the HCP and HCR groups. High temperature/high pressure-processed garlic
      contained a higher amount of S-allyl cysteine than raw garlic (P<.05). The
      results suggest that high temperature/high pressure-processed garlic may be
      useful as a functional food to improve lipid profiles.

PMID- 22404601
TI  - Willingness of the United States general public to participate in kidney paired
      donation.
AB  - BACKGROUND: Availability of kidney paired donation (KPD) is increasing in the
      United States, and a national system through UNOS is forthcoming. However, little
      is known about attitudes toward KPD among the general public, from which donors
      (particularly non-directed) are drawn. METHODS: In a national study, we assessed
      the public's attitudes regarding participation in KPD. RESULTS: Among 845
      randomly selected participants, 85.2% of respondents were either "extremely
      willing" or "very willing" to participate in KPD. Experiences with the medical or
      organ transplant systems, such as undergoing surgery, having a primary medical
      provider, a living will, a friend who donated or received an organ, and
      considering donation after death, were associated with increased willingness.
      However, increased age, male sex, African American race, Hispanic ethnicity,
      distrust of the medical system, and not understanding organ allocation were
      associated with less willingness. CONCLUSIONS: We identify strong support for KPD
      but some important potential barriers to participation which should be considered
      as KPD programs are implemented.

PMID- 22404602
TI  - Foundational issues in risk assessment and risk management.
AB  - In spite of the maturity reached by many of the methods used in risk assessment
      and risk management, broad consensus has not been established on fundamental
      concepts and principles. The risk fields still suffer from a lack of clarity on
      many key scientific pillars. The purpose of this article is to point to this
      situation and through some illustrating examples discuss the challenges that the
      fields here face. Moreover, the purpose of the article is to reflect on how to
      improve the present situation and enhance the risk fields. We argue that the
      establishment of some common scientific pillars as well as a strong and
      continuous research focus on foundational issues are critical success factors.
      The article specifically addresses the role of the peer-reviewed journals and the
      international standards in the fields. We hope that the article can contribute to
      a revitalization of the discussion of foundational issues in risk assessment and
      risk management.

PMID- 22404603
TI  - Mechanisms of suppression of interferon production by porcine reproductive and
      respiratory syndrome virus.
AB  - The recently emerged porcine reproductive and respiratory syndrome virus (PRRSV)
      leads to one of the most economically significant infectious diseases of swine
      worldwide. The virus modulates the host innate and adaptive immunity to escape
      its immune response to facilitate the infection. Interferons (INFs) are principal
      antiviral cytokines, which represent components of the innate immunity and are
      regarded as a bridge between the innate and adaptive immunity. Currently,
      accumulating evidence indicates that the virus has developed various strategies
      to counteract the IFN production. Here, various mechanisms utilized by the virus
      to antagonize the IFN induction are reviewed.

PMID- 22404604
TI  - Evaluation of the in vitro antiretroviral potential of some  Biginelli-type
      pyrimidines.
AB  - Despite the success of highly active antiretroviral therapy, AIDS still remains
      as one of the most important world health problems. Toxicity of current available
      drugs and inevitable emergence of multi-drug resistant strains makes things
      worse. In the present study a series of novel Biginelli-type pyrimidine compounds
      were evaluated as potential anti-human immunodeficiency virus (HIV)-1 agents
      using green fluorescence protein (GFP) reporter single round HIV-1 infection
      assay. The rate of infected cells was monitored by flowcytometry. The effect of
      compounds on the cellular proliferation was considered as the cyotoxicity. The
      anti-HIV-1 active compounds were selected for HIV-1 replication and syncytium
      formation assays. The antiretroviral activity of compounds was measured against
      luciferase reporter A murine leukemia virus (AMLV) virions as the retrovirus
      control. Compounds 2, 5, 6, 8, 11, 12, 13, 17, 18, 20, and 21 were the most
      potent against HIV-1. Compound 8 had the 50% inhibitory concentration (IC50) of
      100 nmol/l for inhibiting HIV-1 replication and 50% cytotoxic concentration
      (CC50) was up to 100 MUmol/l (therapeutic index (TI) >1000). Results show that
      the active compounds were able to inhibit the retrovirus control as well.
      Analysis of structure of the studied compounds proved relationships with their
      anti-HIV-1 effects. Some of the studied compounds seem to be promising anti-HIV-1
      drug candidates. Structural manipulation based on the well-defined structure
      activity relationships might propose some new leads for anti-HIV-1 drug discovery
      programs.

PMID- 22404605
TI  - Characterization of 10 tobacco vein banding mosaic virus isolates from China.
AB  - The complete RNA genome sequences of 10 tobacco vein banding mosaic virus (TVBMV)
      isolates from China were determined using five overlapping cDNA clones. TVBMV was
      divided into three groups for HC-Pro and CP and into two groups for P3 and 6K1.
      With more isolate sequences analyzed, the phylogenetic results suggest that TVBMV
      could be divided into four subgroups based on HC-Pro and CP and into three
      subgroups with P3 and 6K1. Nucleotide sequence diversity analysis showed
      geographical differentiation among the TVBMV isolates. Three of the 10 isolates
      were found to have undergone recombination and new recombination sites were
      identified in the TVBMV genome. All coding genes were under negative selection
      and the population appeared to have remained stable over a long period. This
      study also provides preliminary data on the 3'-untranslated region as potentially
      the best genome sequence for developing transgenic tobacco.

PMID- 22404606
TI  - A set of host proteins interacting with papaya ringspot virus NIa-Pro protein
      identified in a yeast two-hybrid system.
AB  - The protein-protein interactions between viral and host proteins play an
      essential role in plant virus infection and host defense. The potyviral nuclear
      inclusion protein a protease (NIa-Pro) is involved in various steps of viral
      infection. In this study, the host proteins interacting with papaya ringspot
      virus (PRSV) NIa-Pro were screened in a Carica papaya L. plant cDNA library using
      a Sos recruitment two-hybrid system (SRS). We confirmed that the full-length
      EIF3G, FBPA1, FK506BP, GTPBP, MSRB1, and MTL from papaya can interact
      specifically with PRSV NIa-Pro in yeast, respectively. These proteins fufill
      important functions in plant protein translation, biotic and abiotic stress,
      energy metabolism and signal transduction. In this paper, we discuss possible
      functions of interactions between these host proteins and NIa-Pro in PRSV
      infection and their role in host defense. KEYWORDS: Sos recruitment two-hybrid
      system; papaya ringspot virus; NIa-Pro; protein-protein interaction.

PMID- 22404607
TI  - Telbivudine improves the function of myeloid dendritic cells in patients  with
      chronic hepatitis B.
AB  - Dysfunction of dendritic cells (DCs) is considered one of the factors for chronic
      hepatitis B virus (HBV) infection. However the reason for impairment of DCs
      remains elusive. The aim of this study was to investigate the effect of
      telbivudine on number and function of DCs in patients with chronic hepatitis B
      (CHB). After 6 months of telbivudine treatment, the number of plasmacytoid DCs
      (pDCs) increased significantly, nearly to levels observed in normal controls.
      However the capacity of pDCs to produce interferon alpha (IFN-alpha) was not
      enhanced during treatment. Accordingly, monocyte-derived DCs (MoDCs) exhibited a
      markedly enhanced expression of HLA-DR, decreased expression of PD-L1, and
      increased capacity to produce interleukin (IL)-12. These findings suggest that
      the improved function of peripheral myeloid DCs (mDCs) with telbivudine therapy
      in CHB patients may be associated with up-regulated expression of HLA-DR and down
      regulated expression of PD-L1.

PMID- 22404608
TI  - Apoptotic and necrotic changes in cultured murine neurons infected  with equid
      herpesvirus 1.
AB  - Equid herpesvirus 1 (EHV-1), like other members of the Alphaherpesvirinae, is a
      neurotropic virus, that causes latent infections in the nervous system of the
      natural host. All alphaherpesviruses have developed sophisticated strategies to
      interfere with the host cell apoptotic mechanisms, but the ability of EHV-1 to
      induce apoptosis in neurons has not been determined yet. In this study, apoptotic
      and necrotic changes in cultured murine neurons were methods identifying key
      stages of apoptosis. These methods have demonstrated characteristic apoptosis
      features, like DNA fragmentation, chromatin condensation, membrane blebbing and
      cell shrinkage in the infected cells. It seems likely that apoptosis was the
      predominant way of cell death in EHV-1-infected murine neurons. However, we
      showed also that during acute EHV-1 infection the majority of infected neurons
      remained unchanged and survived for more than eight weeks in culture, suggesting
      some protective mechanisms induced by the virus. Furthermore, it was shown that
      infection of neurons with EHV-1 has no significant influence on the level of the
      caspase 3, 7, and 8. We speculate that the control of apoptosis may be the key
      mechanism regulating the balance between productive and latent infection at the
      site of virus persistence.

PMID- 22404609
TI  - Inhibition of hepatitis B virus gene expression by small interfering RNAs
      targeting cccDNA and X antigen.
AB  - To test the possible inhibition of hepatitis B virus (HBV) replication and
      expression by small interfering RNAs (siRNAs) targeting simultaneously covalenthy
      closed circular DNA (dnacccDNA) and X antigen, corresponding recombinant plasmids
      were transfected into HepG2.2.15 cells and the levels of cccDNA, HBXAg, HBcAg,
      and HBeAg were assayed at various times post transfection. As expected, the
      single siRNAs showed marked inhibitory effects but their combination was even
      more efficient. These results provide a new insight into the development of a
      potential anti-HBV strategy of enhancing the efficacy of individual antivirals
      and overcoming the high mutation rate of HBV.

PMID- 22404610
TI  - VP90 of white spot syndrome virus interacts with VP26 and VP28.
AB  - Identification of structural protein relationships is likely to be important for
      virus assembly and anti-WSSV strategies. In this paper, VP90 of white spot
      syndrome virus (WSSV) was characterized. Temporal-transcription analysis showed
      that VP90 is expressed in the late stage of WSSV infection. Far-western and
      matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) assay
      showed that VP90 interacts with VP26 and VP28, two major envelope proteins. Far
      western blot with recombinant VP26 (rVP26), N-terminal end of VP28 (rVP28N) and C
      terminal end of VP28 (rVP28C) provided further evidence for interaction of rVP90
      and rVP26 or rVP28. These results suggest that VP90 is anchored to the envelope
      through interacting with VP26 and VP28.

PMID- 22404611
TI  - Rotavirus receptor proteins Hsc70 and integrin alphavbeta3 are located in the
      lipid microdomains of animal intestinal cells.
AB  - Several cell surface molecules such as integrins, sialic acid and Hsc70 have been
      reported to participate in the process of adsorption and penetration of
      rotaviruses into cells. Some of them have been found in susceptible cell lines
      but not in epithelial cells of natural hosts so that their real role in the
      infection process is unclear. In this study, we attempted to confirm the presence
      of Hsc70 and integrin alphavbeta3 in the cytoplasmic membrane of isolated
      intestinal epithelial cells of pig, mouse and cow. Using immunocytochemistry,
      immunofluorescence, co-immunoprecipitation, ELISA, Western blot analysis and flow
      cytometry we established that in these cells, (i) Hsc70 and integrin alphavbeta3
      formed a complex in lipid raft microdomains of the cytoplasmatic membrane and
      (ii) Hsc70 levels increased after rotavirus infection. These results indicate
      that these molecules act as receptors of rotaviruses in susceptible cells.

PMID- 22404612
TI  - A rapid and highly reliable field-based LAMP assay of canine parvovirus.
AB  - Loop-mediated isothermal amplification (LAMP) is known as a rapid and reliable
      alternative to conventional single-step or nested PCR for detection of genomic
      DNA of various pathogens in clinical samples. In this study, LAMP assay was
      developed for canine parvovirus (CPV) and compared with single-step and nested
      PCR assays. Out of 50 fecal samples from dogs clinically suspected for CPV
      infections, 19 were found positive by single-step PCR, 22 by nested PCR and 26 by
      LAMP. LAMP products were subjected to restriction analysis and sequencing to
      check their specificity. LAMP assay turned out to be a rapid and fairly
      reproducible method, did not amplify other common canine pathogens and was more
      sensitive than nested PCR assay. Therefore, it can be regarded as a highly
      reliable method for routine field diagnosis of CPV infection. KEYWORDS: canine
      parvovirus; nested polymerase chain reaction; loop-mediated isothermal
      amplification; sensitivity; specificity.

PMID- 22404613
TI  - Analysis of rice stripe virus whole-gene expression in rice and in the small
      brown planthopper by real-time quantitative PCR.
AB  - Rice stripe virus (RSV) is a typical member of the Tenuivirus genus, which is
      transmitted mainly by the small brown planthopper (SBPH) in a persistent,
      circulative-propagative manner. At present, expression levels of viral genes in
      rice and in SBPH remain unclear. In this study, we investigated RSV gene
      expression in RSV-infected rice tissues and in viruliferous SBPH using a
      sensitive and reliable real-time quantitative PCR (Q-PCR) method. The results
      revealed that NS3 gene exhibited the highest abundant expression in both, rice
      plants and SBPH. Disease-specific protein (SP) gene was the only gene with
      highest expression in rice, but not in SBPH. The expression levels of other genes
      were lower than SP and approximately equal to each other in both, in rice and
      SBPH. RNA-dependent RNA polymerase (RdRp) in SBPH was present in a notably low
      level. Furthermore, our results also provided a basis for further investigation
      on how RSV coordinates its own gene expression in the interactions with its plant
      and insect hosts.

PMID- 22404614
TI  - Rapid detection and quantification of Orf virus from infected scab materials of
      sheep and goats.

PMID- 22404615
TI  - Human adenovirus infection in patients subjected to allogeneic hematopoietic stem
      cell transplantation--a three-year single center study.

PMID- 22404616
TI  - A small peptide sequence is sufficient for initiating kinesin-1 activation
      through part of TPR region of KLC1.
AB  - Kinesin-1 anterogradely transports vesicles containing cargo proteins when a
      protein-protein interaction activates it from an inhibited state. The C-terminal
      cytoplasmic region of kinesin-1 cargo protein Alcadeinalpha (Alcalpha) interacts
      with the KLC1 subunit's tetratricopeptide repeat (TPR) region, activating kinesin
      1's association with vesicles and anterograde transport. We found that either of
      two 10-amino-acid WD motifs in Alcalpha cytoplasmic region was necessary and
      sufficient to initiate this activation. An artificial transmembrane protein
      containing either WD motif induced kinesin-1's vesicular association and
      anterograde transport in a KLC-dependent manner, even in the normally inhibiting
      presence of excess KLC1, thus allowing us to analyze the KLC1 TPR-WD functional
      interaction in detail in vivo. A part of TPR region was dispensable for the WD
      motifs' activation of kinesin-1 and transport, indicating that only part of the
      TPR structure is required for this function in vivo. For a different kinesin-1
      cargo protein, JIP1, an 11-amino-acid C-terminal region was sufficient to recruit
      KLC1 to vesicles, but did not activate transport. These observations suggest that
      structurally different TPR-interacting peptides may have different effects on
      kinesin-1. This mechanism may partly explain how kinesin-1 can organize the
      transport of a wide variety of cargo molecules.

PMID- 22404619
TI  - Astrocytes: more than just glue.

PMID- 22404617
TI  - Efficacy of systemic therapies for moderate-to-severe psoriasis: a systematic
      review and meta-analysis of long-term treatment.
AB  - BACKGROUND: Despite the chronicity of psoriasis, most systematic reviews focus on
      short-term treatment. METHODS: The systematic search strategy and results from
      the German Psoriasis Guidelines were adapted. To update the data a literature
      search in Medline, Embase and the Cochrane Library was conducted. The proportion
      of participants achieving >=75% decrease in Psoriasis Area and Severity Index
      (PASI) as well as Dermatology Life Quality Index (DLQI) reduction at different
      time points were assessed. Trials were summarized with respect to time periods
      and study designs. Suitable trials were included in a meta-analysis. Particular
      attention was paid to statistical approaches of handling dropouts. RESULTS: A
      total of 33 articles including 27 trials totaling 6575 patients with active
      treatment were included in the systematic review. Seven randomized controlled
      trials were eligible for the meta-analysis. Over a 24 week treatment period
      infliximab [risk difference (RD) 78%, 95% confidence interval (CI) 72-83%] and
      ustekinumab 90 mg every 12 weeks (RD 77%, 95% CI 71-83%) were the most
      efficacious treatments. Adalimumab (RD: 60%, 95% CI 45-74%) showed results within
      the range of different etanercept dosages (etanercept 50 mg once weekly: RD 62%,
      95% CI, 52-72%), (etanercept 25 mg twice weekly: RD 45%, 95% CI 34-56%),
      (etanercept 50 mg twice weekly: RD 56%, 95% CI 49-62%) and (etanercept 50 mg
      twice weekly until week 12, then 25 mg twice weekly: RD 50%, 95% CI 42-57%).
      After 24 weeks a decrease in efficacy for inflximab, adalimumab and etanercept
      was observed. CONCLUSIONS: More sufficient data is required to draw reliable
      conclusions in extended long-term treatment and head-to-head comparisons are
      necessary.

PMID- 22404620
TI  - Survival in children with severe cerebral palsy: a further international
      comparison.

PMID- 22404621
TI  - Blended fertilizers as draw solutions for fertilizer-drawn forward osmosis
      desalination.
AB  - In fertilizer-drawn forward osmosis (FDFO) desalination, the final nutrient
      concentration (nitrogen, phosphorus, potassium (NPK)) in the product water is
      essential for direct fertigation and to avoid over fertilization. Our study with
      11 selected fertilizers indicate that blending of two or more single fertilizers
      as draw solution (DS) can achieve significantly lower nutrient concentration in
      the FDFO product water rather than using single fertilizer alone. For example,
      blending KCl and NH(4)H(2)PO(4) as DS can result in 0.61/1.35/1.70 g/L of N/P/K,
      which is comparatively lower than using them individually as DS. The nutrient
      composition and concentration in the final FDFO product water can also be
      adjusted by selecting low nutrient fertilizers containing complementary nutrients
      and in different ratios to produce prescription mixtures. However, blending
      fertilizers generally resulted in slightly reduced bulk osmotic pressure and
      water flux in comparison to the sum of the osmotic pressures and water fluxes of
      the two individual DSs as used alone. The performance ratio or PR (ratio of
      actual water flux to theoretical water flux) of blended fertilizer DS was
      observed to be between the PR of the two fertilizer solutions tested
      individually. In some cases, such as urea, blending also resulted in significant
      reduction in N nutrient loss by reverse diffusion in presence of other fertilizer
      species.

PMID- 22404622
TI  - Melatonin suppresses migration and invasion via inhibition of oxidative stress
      pathway in glioma cells.
AB  - Melatonin, an indolamine produced and secreted predominately by the pineal gland,
      exhibits a variety of physiological functions, possesses antioxidant and
      antitumor properties. In this study, we have shown that pharmacologic
      concentration (1mm) of melatonin significantly reduced cell migration and
      invasion of T98G and U251 glioma cells after 24-hr treatment and inhibited
      expression of matrix metalloproteinase 2 (MMP 2) and MMP 9. The melatonin
      inhibition of cell migration and invasion was associated with its reduction of
      intracellular basal free radical generation. Melatonin at pharmacologic
      concentration also inhibited the constitutive activation of the reactive oxygen
      species downstream transcription factor nuclear factor kappa-light-chain-enhancer
      of activated B cells (NF-kappaB). Furthermore, pyrrolidine dithiocarbamate, a NF
      kappaB-specific inhibitor, at 10MUm displayed anti-migration and invasion effects
      and inhibition of MMP 2 and MMP 9 expression resembling that of melatonin. Taken
      together, it is concluded that inhibition of migration and invasion of glioma
      cells by melatonin is associated with the latter in its inhibition of oxidative
      stress pathway. This suggests a potential therapeutic application of melatonin in
      the treatment of glioma.

PMID- 22404623
TI  - A research of service outcomes in Taiwan: the role of patients' quality
      perceptions and wait time.
AB  - Wait time is a continuing issue in healthcare services. U.S. studies reveal wait
      time is inversely related to healthcare service outcome as well as patient
      behavior and attitudes. However, Taiwan, despite being an important center for
      global healthcare services, has not been the subject of much research attention
      regarding wait time and its impact on patient perceptions and behavior. In the
      authors' exploratory study, patients in Taiwan completed a self-report
      questionnaire on how wait time and service quality characteristics relate to
      service outcome. Results indicate the influence of healthcare service quality and
      wait time on service outcome. Contributions, limitations, and research and
      managerial implications are discussed.

PMID- 22404624
TI  - Converting data into information.
AB  - Improving healthcare in the 21st century will depend on how well vast amounts of
      data are mined. However, converting data contained in multiple hospital and
      clinical databases into information that can be used for clinical decision
      support is a complex task. The process involves a combination of cultural and
      technological steps that are time-consuming and resource-intensive. The authors
      describe one hospital's long journey toward becoming a data-driven organization.

PMID- 22404625
TI  - Service quality in the public sector hospitals: a study in India.
AB  - Most studies on service quality have been conducted in the context of the private
      sector of the economy. In fact, in the healthcare setting, for a long time,
      public-sector hospitals were not expected to excel in the provision of service
      quality. In a country such as India, even now, public-sector hospital staffs
      enjoy relatively higher salaries, flexible work schedules, and secure employment
      until retirement. Because patients do not pay for most services, normally they
      are concerned only about the quality of the core product. The authors indicate
      that, even in the public sector context, the quality of the physician and that of
      the clinical support staff significantly impact patient satisfaction. However,
      the quality of nonclinical support staff is not found to have any significant
      effect on patient satisfaction.

PMID- 22404627
TI  - Ubiquitin-like proteins.
AB  - The eukaryotic ubiquitin family encompasses nearly 20 proteins that are involved
      in the posttranslational modification of various macromolecules. The ubiquitin
      like proteins (UBLs) that are part of this family adopt the beta-grasp fold that
      is characteristic of its founding member ubiquitin (Ub). Although structurally
      related, UBLs regulate a strikingly diverse set of cellular processes, including
      nuclear transport, proteolysis, translation, autophagy, and antiviral pathways.
      New UBL substrates continue to be identified and further expand the functional
      diversity of UBL pathways in cellular homeostasis and physiology. Here, we review
      recent findings on such novel substrates, mechanisms, and functions of UBLs.

PMID- 22404626
TI  - RNA polymerase II elongation control.
AB  - Regulation of the elongation phase of transcription by RNA polymerase II (Pol II)
      is utilized extensively to generate the pattern of mRNAs needed to specify cell
      types and to respond to environmental changes. After Pol II initiates, negative
      elongation factors cause it to pause in a promoter proximal position. These
      polymerases are poised to respond to the positive transcription elongation factor
      P-TEFb, and then enter productive elongation only under the appropriate set of
      signals to generate full-length properly processed mRNAs. Recent global analyses
      of Pol II and elongation factors, mechanisms that regulate P-TEFb involving the
      7SK small nuclear ribonucleoprotein (snRNP), factors that control both the
      negative and positive elongation properties of Pol II, and the mRNA processing
      events that are coupled with elongation are discussed.

PMID- 22404628
TI  - Ubiquitin and membrane protein turnover: from cradle to grave.
AB  - From the moment of cotranslational insertion into the lipid bilayer of the
      endoplasmic reticulum (ER), newly synthesized integral membrane proteins are
      subject to a complex series of sorting, trafficking, quality control, and quality
      maintenance systems. Many of these processes are intimately controlled by
      ubiquitination, a posttranslational modification that directs trafficking
      decisions related to both the biosynthetic delivery of proteins to the plasma
      membrane (PM) via the secretory pathway and the removal of proteins from the PM
      via the endocytic pathway. Ubiquitin modification of integral membrane proteins
      (or "cargoes") generally acts as a sorting signal, which is recognized, captured,
      and delivered to a specific cellular destination via specialized trafficking
      events. By affecting the quality, quantity, and localization of integral membrane
      proteins in the cell, defects in these processes contribute to human diseases,
      including cystic fibrosis, circulatory diseases, and various neuropathies. This
      review summarizes our current understanding of how ubiquitin modification
      influences cargo trafficking, with a special emphasis on mechanisms of quality
      control and quality maintenance in the secretory and endocytic pathways.

PMID- 22404629
TI  - Discovery, biosynthesis, and engineering of lantipeptides.
AB  - Aided by genome-mining strategies, knowledge of the prevalence and diversity of
      ribosomally synthesized natural products (RNPs) is rapidly increasing. Among
      these are the lantipeptides, posttranslationally modified peptides containing
      characteristic thioether cross-links imperative for bioactivity and stability.
      Though this family was once thought to be a limited class of antimicrobial
      compounds produced by gram-positive bacteria, new insights have revealed a much
      larger diversity of activity, structure, biosynthetic machinery, and producing
      organisms than previously appreciated. Detailed investigation of the enzymes
      responsible for installing the posttranslational modifications has resulted in
      improved in vivo and in vitro engineering systems focusing on enhancement of the
      therapeutic potential of these compounds. Although dozens of new lantipeptides
      have been isolated in recent years, bioinformatic analyses indicate that many
      hundreds more await discovery owing to the widespread frequency of lantipeptide
      biosynthetic machinery in bacterial genomes.

PMID- 22404631
TI  - Introduction to theme "Chromatin, epigenetics, and transcription".
AB  - Transcriptional regulation in eukaryotes depends on a complex network of
      interactions between RNA polymerases and a host of transcription factors and
      coregulators that control their activity during transcription initiation and
      elongation. Among these are an enormous variety of enzymes and proteins that
      modulate chromatin structure via changes in DNA methylation, histone
      modifications, and nucleosome location. This volume of the Annual Review of
      Biochemistry contains a set of four reviews addressing the interplay between
      mechanisms that regulate DNA methylation, chromatin structure, and transcription.

PMID- 22404630
TI  - Ubiquitin and proteasomes in transcription.
AB  - Regulation of gene transcription is vitally important for the maintenance of
      normal cellular homeostasis. Failure to correctly regulate gene expression, or to
      deal with problems that arise during the transcription process, can lead to
      cellular catastrophe and disease. One of the ways cells cope with the challenges
      of transcription is by making extensive use of the proteolytic and nonproteolytic
      activities of the ubiquitin-proteasome system (UPS). Here, we review recent
      evidence showing deep mechanistic connections between the transcription and
      ubiquitin-proteasome systems. Our goal is to leave the reader with a sense that
      just about every step in transcription-from transcription initiation through to
      export of mRNA from the nucleus-is influenced by the UPS and that all major arms
      of the system--from the first step in ubiquitin (Ub) conjugation through to the
      proteasome-are recruited into transcriptional processes to provide regulation,
      directionality, and deconstructive power.

PMID- 22404632
TI  - Programming of DNA methylation patterns.
AB  - DNA methylation represents a form of genome annotation that mediates gene
      repression by serving as a maintainable mark that can be used to reconstruct
      silent chromatin following each round of replication. During development,
      germline DNA methylation is erased in the blastocyst, and a bimodal pattern is
      established anew at the time of implantation when the entire genome gets
      methylated while CpG islands are protected. This brings about global repression
      and allows housekeeping genes to be expressed in all cells of the body.
      Postimplantation development is characterized by stage- and tissue-specific
      changes in methylation that ultimately mold the epigenetic patterns that define
      each individual cell type. This is directed by sequence information in DNA and
      represents a secondary event that provides long-term expression stability.
      Abnormal methylation changes play a role in diseases, such as cancer or fragile X
      syndrome, and may also occur as a function of aging or as a result of
      environmental influences.

PMID- 22404633
TI  - Structure and regulation of soluble guanylate cyclase.
AB  - Nitric oxide (NO) is an essential signaling molecule in biological systems. In
      mammals, the diatomic gas is critical to the cyclic guanosine monophosphate
      (cGMP) pathway as it functions as the primary activator of soluble guanylate
      cyclase (sGC). NO is synthesized from l-arginine and oxygen (O(2)) by the enzyme
      nitric oxide synthase (NOS). Once produced, NO rapidly diffuses across cell
      membranes and binds to the heme cofactor of sGC. sGC forms a stable complex with
      NO and carbon monoxide (CO), but not with O(2). The binding of NO to sGC leads to
      significant increases in cGMP levels. The second messenger then directly
      modulates phosphodiesterases (PDEs), ion-gated channels, or cGMP-dependent
      protein kinases to regulate physiological functions, including vasodilation,
      platelet aggregation, and neurotransmission. Many studies are focused on
      elucidating the molecular mechanism of sGC activation and deactivation with a
      goal of therapeutic intervention in diseases involving the NO/cGMP-signaling
      pathway. This review summarizes the current understanding of sGC structure and
      regulation as well as recent developments in NO signaling.

PMID- 22404634
TI  - Is Huntington's disease associated with deficits in theory of mind?
AB  - OBJECTIVES: People with Huntington's disease (HD) can exhibit interpersonal
      difficulties and deficits in recognizing emotional facial expressions. We
      investigated whether individuals with HD exhibit impairments in the understanding
      of other people's mental states, an aspect of Theory of Mind (ToM). MATERIALS AND
      METHODS: Sixteen patients with HD and sixteen healthy controls completed two ToM
      tasks. One task involved recognising socially inappropriate behaviour and the
      other task required participants to judge complex mental states from photographs
      of people's eyes alone. To assess relationships between executive function and
      ToM, participants completed measures of verbal fluency, working memory and
      inhibition. The Problem Behaviours Assessment-short form (Neuropsychiatry
      Neuropsychol Behav Neurol, 14, 2001and 219) was completed twice using information
      from patients and their close relatives (where possible) to identify
      relationships between ToM impairment and behavioural problems. RESULTS: Patients
      with HD made significantly more errors on ToM tasks than controls, exhibiting
      difficulties in judging the social appropriateness of story character's behaviour
      and problems inferring complex mental states from photographs of people's eyes.
      Patients with HD also exhibited executive dysfunction. However, there was little
      evidence that executive impairments were related to ToM deficits. No correlations
      were apparent between problem behaviours and ToM errors. CONCLUSIONS: HD is
      associated with deficits in ToM. Furthermore, some of patients' ToM difficulties
      appear independent of executive dysfunction.

PMID- 22404635
TI  - Damping factor links periodic focusing and uniform field ion mobility for
      accurate determination of collision cross sections.
AB  - The methodology for obtaining accurate ion-neutral collision cross section
      (Omega) values for peptides and proteins using periodic focusing ion mobility
      spectrometry (PF IMS) is presented. A mobility dampening factor (represented by
      the term alpha) is introduced to account for the relative increase in ion-neutral
      collisions in PF IMS compared to uniform field ion mobility spectrometry (UF IMS)
      for equivalent operating conditions. The results show that alpha may be easily
      quantified both theoretically and empirically for a specific PF IMS design
      operating at a given pressure based upon the charge state of the analyte. By
      simply incorporating an alpha term into traditional UF IMS expressions, accurate
      Omega values were obtained with excellent agreement (<=4% difference) compared to
      UF IMS measurements found in the current literature.

PMID- 22404636
TI  - Beware the 'Loughborough School' of Social Psychology? Interaction and the
      politics of intervention.
AB  - The authors explain the attractions of applying discursive psychology (DP) and
      conversation analysis (CA) by reporting three different examples of their
      engagement with practitioners and clients. Along the way, a case is made for
      separating DP/CA from other kinds of qualitative analysis in social psychology,
      and for deconstructing some commonly held misunderstandings and caricatures of
      DP/CA.

PMID- 22404637
TI  - Seed after-ripening and dormancy determine adult life history independently of
      germination timing.
AB  - * Seed dormancy can affect life history through its effects on germination time.
      Here, we investigate its influence on life history beyond the timing of
      germination. * We used the response of Arabidopsis thaliana to chilling at the
      germination and flowering stages to test the following: how seed dormancy affects
      germination responses to the environment; whether variation in dormancy affects
      adult phenology independently of germination time; and whether environmental cues
      experienced by dormant seeds have an effect on adult life history. * Dormancy
      conditioned the germination response to low temperatures, such that prolonged
      periods of chilling induced dormancy in nondormant seeds, but stimulated
      germination in dormant seeds. The alleviation of dormancy through after-ripening
      was associated with earlier flowering, independent of germination date.
      Experimental dormancy manipulations showed that prolonged chilling at the seed
      stage always induced earlier flowering, regardless of seed dormancy.
      Surprisingly, this effect of seed chilling on flowering time was observed even
      when low temperatures did not induce germination. * In summary, seed dormancy
      influences flowering time and hence life history independent of its effects on
      germination timing. We conclude that the seed stage has a pronounced effect on
      life history, the influence of which goes well beyond the timing of germination.

PMID- 22404638
TI  - Post-diagnostic kinetics of the (1 -> 3)-beta-D-glucan assay in invasive
      aspergillosis, invasive candidiasis and Pneumocystis jirovecii pneumonia.
AB  - The kinetics of serum (1 -> 3)-beta-d-glucan (BG) following the diagnosis of
      invasive fungal disease and administration of antifungal therapy are poorly
      characterized. It is unknown whether early BG changes have prognostic
      implications. We assessed the post-diagnostic kinetics of BG in patients with an
      initial serum BG >=80 pg/mL and at least one additional post-diagnostic BG value
      in the setting of invasive aspergillosis (IA, n=69), invasive candidiasis (IC,
      n=40), or Pneumocystis jirovecii pneumonia (PCP, n = 18), treated with antifungal
      therapy. Clinical failure of antifungal therapy and mortality were assessed at 6
      and 12 weeks, and Cox modelling was used to assess the hazard of initial BG and
      change in BG at 1 or 2 weeks for these outcomes. In patients with at least two BG
      values, median initial BG was >500 pg/mL (interquartile range (IQR) 168 to >500;
      range 80 to >500) in IA, 136 pg/mL (IQR 88 to >500; range 31 to >500) in IC and
      >500 pg/mL (IQR 235 to >500; range 86 to >500) in PCP. In patients with at least
      two BG values through to 1 week after diagnosis, overall 1-week decline in BG was
      0 pg/mL (IQR 0-53) in IA, 0 (IQR - 65 to 12) in IC and 17 (IQR 0-82) in PCP. Most
      patients with BG values through 6 and 12 weeks had persistent levels >80 pg/mL.
      Initial BG and the early trajectory of BG were not predictive of 6-week or 12
      week clinical failure or mortality. Whereas BG eventually declines in patients
      with IA, IC and PCP, it lacks prognostic value within a clinically meaningful
      time frame.

PMID- 22404639
TI  - Splenectomy and/or cyclophosphamide as salvage therapies in thrombotic
      thrombocytopenic purpura: the French TMA Reference Center experience.
AB  - BACKGROUND: The objective was to assess the efficacy and safety of splenectomy
      and cyclophosphamide as salvage therapies in severe thrombotic thrombocytopenic
      purpura (TTP). STUDY DESIGN AND METHODS: During a 10-year period, patients who
      did not improve with plasma exchanges, steroids, vincristine, and/or rituximab
      were considered for splenectomy or cyclophosphamide. Patients with a documented
      severe (<10% of normal value) acquired ADAMTS13 deficiency are reported here.
      RESULTS: Eighteen patients with a severe acquired ADAMTS13 deficiency required a
      salvage therapy. Thirteen patients had a splenectomy 19 (interquartile range
      [IQR], 10-51) days after TTP diagnosis. One patient died the day after
      splenectomy. The remaining patients improved platelets (PLTs) until Day 6, along
      with a rapid and major lactate dehydrogenase improvement. Six patients, however,
      subsequently experienced a transient worsening. Durable PLT count recovery in
      survivors was observed within 13 (IQR, 11.5-25.5) days. Postoperative
      complications included thromboembolic events (two cases) and infections (five
      cases). Five patients received pulses of cyclophosphamide 12 (IQR, 12-15) days
      after TTP diagnosis. All patients recovered PLTs 10 (IQR, 9-24) days after the
      first pulse and two experienced a transient worsening. Three patients experienced
      infections. Three relapses occurred 5 months, 2.5 years, and 4.5 years after
      splenectomy and one relapse occurred 3.5 years after cyclophosphamide. After a
      2.5 (IQR, 0.75-6.2)-year follow-up, the overall survival was 94%. CONCLUSION:
      Cyclophosphamide and splenectomy provide comparable high remission rates in
      severe TTP with acceptable side effects and should be considered in the more
      severe patients who do not improve with other therapies.

PMID- 22404640
TI  - Tobacco expenditure, smoking-induced deprivation and financial stress: results
      from the International Tobacco Control (ITC) Four-Country Survey.
AB  - INTRODUCTION AND AIMS: While higher tobacco prices lead to a reduction in smoking
      prevalence, there is a concern that paying more for cigarettes can lead to excess
      financial burden. Our primary aim was to examine the association of daily
      cigarette expenditure with smoking-induced deprivation (SID) and financial stress
      (FS). DESIGN AND METHODS: We used data from wave 7 (2008-2009) of the
      International Tobacco Control (ITC) Four-Country Survey which is a survey of
      smokers in Canada, the USA, the UK and Australia (n = 5887). Logistic regressions
      were used to assess the association of daily cigarette expenditure with SID and
      FS. RESULTS: In multivariate analyses, a one standard deviation increase in daily
      cigarette expenditure was associated with an increase of 24% (P = 0.004) in the
      probability of experiencing SID. While we found no association between daily
      cigarette expenditure and FS, we found that SID is a strong predictor of FS (odds
      ratio 6.25; P < 0.001). This suggests that cigarette expenditure indirectly
      affects FS through SID. Results showed no evidence of an interaction between
      cigarette expenditure and income or education in their effect on SID or FS.
      CONCLUSIONS: Our results imply that spending more on tobacco may result in SID
      but surprisingly has no direct effect on FS. While most smokers may be adjusting
      their incomes and consumption to minimise FS, some fail to do so occasionally as
      indexed by the SID measure. Future studies need to prospectively examine the
      effect of increased tobacco expenditure on financial burden of smokers.

PMID- 22404641
TI  - Oophorectomy in children. Who and why: 13-year experience in a single centre.
AB  - AIM: Oophorectomy performed in children is extremely uncommon. We aimed to
      investigate the disease pattern and the association between the underlying
      pathology and the clinical presentation among those patients who had their
      ovaries removed in their childhood. METHODS: A retrospective study was performed
      on 41 consecutive children who underwent oophorectomy in a tertiary referral
      centre in the period between June 1995 and May 2008. RESULTS:   The median age
      was 11 years, ranged from 11 weeks to 15 years at the time of surgery. The
      primary presentations were acute lower abdominal pain (n= 20), progressive
      abdominal distension or abdominal mass (n= 13), chronic abdominal pain (n= 3),
      irregular menses (n= 1), antenatal diagnosis (n= 3) and incidental finding (n=
      1). Ultrasound examination was performed in 31 patients and positive findings of
      ovarian pathology were found in all but one examination. Twenty cases of ovarian
      torsion were confirmed intra-operatively. Patients presenting with acute
      abdominal pain were more likely to have torsion than other presentations (P <
      0.01). Non-neoplastic conditions and ovarian neoplasms were found in 11 and 30
      patients, respectively. The most common neoplasm was mature teratoma (52%).
      Malignant neoplasms included immature teratoma (n= 3), dysgerminoma (n= 1), mixed
      dysgerminoma + yolk sac tumour (n= 2), yolk sac tumour (n= 2) and juvenile
      granulose cell tumour (n= 1). Malignant neoplasms were found to have more chronic
      presentation and less torsion than benign pathologies (P < 0.05). CONCLUSION:
      Although ovarian pathology is uncommon in children, a girl presenting with acute
      lower abdominal pain or progressive abdominal distension should raise the
      suspicion and prompt immediate investigation to rule out ovarian torsion or
      ovarian neoplasms.

PMID- 22404642
TI  - Chemical constituents of Euphorbia hyberna L. (Euphorbiaceae).
AB  - Chemical investigation of the aerial part and the roots of Euphorbia hyberna L.
      subs. hyberna. resulted in the isolation and identification of four triterpenoids
      (3beta-O-octadecanoyllupeol (1), glut-5-en-3beta-ol (2), 24-methylenecicloartan
      3beta-ol (3) and cicloart-23-ene-3beta,25-diol (6)) along with the phenolic
      compounds ellagic acid (4) and 3,3'-di-O-methylellagic acid (7). Although these
      are all known compounds, this is the first report of their isolation from this
      plant. Their structures were elucidated on the basis of spectral methods,
      including 2D NMR experiences, and confirmed by comparing with the literature
      data.

PMID- 22404643
TI  - Long-term warming alters the composition of Arctic soil microbial communities.
AB  - Despite the importance of Arctic soils in the global carbon cycle, we know very
      little of the impacts of warming on the soil microbial communities that drive
      carbon and nutrient cycling in these ecosystems. Over a 2-year period, we
      monitored the structure of soil fungal and bacterial communities in organic and
      mineral soil horizons in plots warmed by greenhouses for 18 years and in control
      plots. We found that microbial communities were stable over time but strongly
      structured by warming. Warming led to significant reductions in the evenness of
      bacterial communities, while the evenness of fungal communities increased
      significantly. These patterns were strongest in the organic horizon, where
      temperature change was greatest and were associated with a significant increase
      in the dominance of the Actinobacteria and significant reductions in the
      Gemmatimonadaceae and the Proteobacteria. Greater evenness of the fungal
      community with warming was associated with significant increases in the
      ectomycorrhizal fungi, Russula spp., Cortinarius spp., and members of the
      Helotiales suggesting that increased growth of the shrub Betula nana was an
      important mechanism driving this change. The shifts in soil microbial community
      structure appear sufficient to account for warming-induced changes in nutrient
      cycling in Arctic tundra as climate warms.

PMID- 22404644
TI  - Acquired haemophilia in a patient treated with interferon-alpha for hepatitis C
      infection.

PMID- 22404645
TI  - Genome-wide association genetics of an adaptive trait in lodgepole pine.
AB  - Pine cones that remain closed and retain seeds until fire causes the cones to
      open (cone serotiny) represent a key adaptive trait in a variety of pine species.
      In lodgepole pine, there is substantial geographical variation in serotiny across
      the Rocky Mountain region. This variation in serotiny has evolved as a result of
      geographically divergent selection, with consequences that extend to forest
      communities and ecosystems. An understanding of the genetic architecture of this
      trait is of interest owing to the wide-reaching ecological consequences of
      serotiny and also because of the repeated evolution of the trait across the
      genus. Here, we present and utilize an inexpensive and time-effective method for
      generating population genomic data. The method uses restriction enzymes and PCR
      amplification to generate a library of fragments that can be sequenced with a
      high level of multiplexing. We obtained data for more than 95,000 single
      nucleotide polymorphisms across 98 serotinous and nonserotinous lodgepole pines
      from three populations. We used a Bayesian generalized linear model (GLM) to test
      for an association between genotypic variation at these loci and serotiny. The
      probability of serotiny varied by genotype at 11 loci, and the association
      between genotype and serotiny at these loci was consistent in each of the three
      populations of pines. Genetic variation across these 11 loci explained 50% of the
      phenotypic variation in serotiny. Our results provide a first genome-wide
      association map of serotiny in pines and demonstrate an inexpensive and efficient
      method for generating population genomic data.

PMID- 22404646
TI  - EPS Prize Lecture. Licking and liking: the assessment of hedonic responses in
      rodents.
AB  - Affective processes are a key determinant of behaviour: At its simplest, liked
      stimuli are approached while disliked stimuli are avoided. Although assessing
      hedonic responses in nonverbal animals can be difficult, one relatively tractable
      approach relies on detailed analyses of rodents' consummatory behaviour. Rodents
      typically produce rhythmic sets of licks that can be grouped into clusters on the
      basis of the intervals between licks. The mean number of licks in a cluster
      (cluster size) is directly related to the concentration of palatable and
      unpalatable solutions. These relationships suggest that lick cluster size might
      be a useful index of an animal's hedonic reaction to the solution being consumed.
      I begin by reviewing studies of conditioned flavour preference and aversion that
      support the idea that lick cluster size can provide useful information about
      rats' hedonic reactions. I then describe how this methodology has been used to
      address previously intractable issues in the investigation of contrast effects as
      well as revealing an analogue of effort justification effects that, in humans,
      are commonly explained in terms of cognitive dissonance reduction. Finally, I
      consider how lick analysis might provide information about hedonic responses in
      animal models of human psychiatric disorders. In all these cases, how an animal
      did something was particularly informative about why it was doing it.

PMID- 22404647
TI  - Working memory capacity and visual attention: top-down and bottom-up guidance.
AB  - Previous studies have indicated that working memory capacity (WMC) is related to
      visual attention when selection of critical information must be made in the face
      of distraction. The present study examines whether WMC-related differences in
      flanker task performance might be decreased by displays that are designed to
      support bottom-up guidance of attention. Participants were required to respond to
      a centrally located target while ignoring a peripheral flanker. In one condition,
      bottom-up support was provided by embedding the target in a row of zeros. In
      another condition, the zeros were removed, thus emphasizing the role of top-down
      attention in selecting spatially defined information. It was found that the
      inclusion of zeros led to the elimination of WMC-related flanker effects. We
      conclude that bottom-up attentional guidance can attenuate the role of WMC in
      selective attention.

PMID- 22404648
TI  - In-cell fluorescence activation and labeling of proteins mediated by FRET
      quenched split inteins.
AB  - Methods to visualize, track, and modify proteins in living cells are central for
      understanding the spatial and temporal underpinnings of life inside cells.
      Although fluorescent proteins have proven to be extremely useful for in vivo
      studies of protein function, their utility is inherently limited because their
      spectral and structural characteristics are interdependent. These limitations
      have spurred the creation of alternative approaches for the chemical labeling of
      proteins. We report in this work the use of fluorescence resonance emission
      transfer (FRET)-quenched DnaE split inteins for the site-specific labeling and
      concomitant fluorescence activation of proteins in living cells. We have
      successfully employed this approach for the site-specific in-cell labeling of the
      DNA binding domain (DBD) of the transcription factor YY1 using several human cell
      lines. Moreover, we have shown that this approach can be also used for modifying
      proteins to control their cellular localization and potentially alter their
      biological activity.

PMID- 22404649
TI  - Increased CCL18 expression in patients with cutaneous T-cell lymphoma:
      association with disease severity and prognosis.
AB  - BACKGROUND: CC chemokine ligand (CCL) 18 is expressed by monocytes and dendritic
      cells (DCs), and has potent chemotactic activity for T cells, B cells and DCs.
      CCL18 expression is up-regulated in lesional skin of atopic dermatitis and
      bullous pemphigoid, suggesting its important roles in the development of these
      skin diseases. OBJECTIVE: To investigate roles of CCL18 in cutaneous T-cell
      lymphoma (CTCL). METHODS: The CCL18 messenger RNA (mRNA) expression in CTCL skin
      (n = 21) and in normal skin (n = 7) was examined by quantitative RT-PCR. CCL18
      expression was also examined by immunohistochemistry. Serum CCL18 levels were
      measured in 38 patients with CTCL and 20 healthy controls by enzyme-linked
      immunosorbent assay. We also analysed correlation between serum CCL18 levels and
      other clinical and laboratory data. RESULTS: The CTCL lesional skin contained
      higher levels of CCL18 mRNA than normal skin. CCL18 was expressed by dermal
      macrophages and DCs in CTCL skin. Serum CCL18 levels in patients with CTCL were
      significantly higher than those of healthy controls and correlated with types of
      skin lesions. They also significantly correlated with modified severity-weighted
      assessment scores, serum sIL-2R, LDH, IL-4, IL-10, IL-31, CCL17 and CCL26 levels.
      Patients with high serum levels of CCL18 showed significantly poor prognosis
      compared with those with low CCL18 levels. CONCLUSION: CCL18 mRNA is up-regulated
      in CTCL lesional skin, and serum CCL18 levels are significantly increased and
      correlated with the severity of CTCL. These results suggest that CCL18 may be
      associated with the development of CTCL.

PMID- 22404650
TI  - Too scared or too capable? Why do college students stay away from the H1N1
      vaccine?
AB  - Although college students were among the populations that had the highest
      frequency of infection for H1N1 influenza, only 8% of them received H1N1 vaccine
      this past flu season nationwide. During the peak of this pandemic, information
      about H1N1 vaccine was widely available. However, knowledge test and behavioral
      data indicated that most college students were not equipped with basic facts
      about H1N1 and the H1N1 vaccine. To investigate socio-psychological factors that
      might have deterred this high-risk population from learning about and getting the
      H1N1 vaccine, this study tested the utility of a risk information seeking model
      in addressing this health communication problem. Data collected from an online
      survey of 371 college students showed that respondents seemed to overestimate how
      much they knew about the vaccine. Risk information seeking, however, positively
      influenced their intentions to get the vaccine. Results suggested that to
      communicate effectively to this population, it is important to emphasize the
      difference between perceived knowledge and actual knowledge, monitor emotional
      responses to potential risks, and promote getting flu vaccination as a socially
      desirable behavior.

PMID- 22404654
TI  - Efficacy of homologous inositol hexaphosphate-loaded red blood cells in sickle
      transgenic mice.
AB  - Patients with sickle cell disease (SCD) can present several severe symptoms
      during their lifetime, including painful events due to vascular occlusion (VOC).
      Even though multiple factors are involved in VOC, hypoxia is the most important
      triggering factor. Inositol hexaphosphate (IHP) reduces the oxygen-haemoglobin
      affinity thus improving the oxygen release in the blood stream and in the
      tissues. Thus, IHP-loaded homologous red blood cells (IHP-RBCs) could be able to
      reduce disorders in SCD. The effectiveness of treatment was assessed in two types
      of SCD transgenic mice (BERK and SAD). The administration of four repeated
      injections of IHP-RBCs in BERK mice resulted in an improved survival rate and
      brain development, prevention of severe anaemia and a greatly lowered risk of
      VOC. After one injection of IHP-RBCs, SAD mice were subjected to acute hypoxic
      stress. Analysis of the lungs revealed significantly decreased mRNA levels of
      molecules involved in intravascular disorders. Our results showed that
      transfusion of homologous IHP-RBCs, by increasing the oxygen delivery, reduces
      SCD disorders in sickle transgenic mice.

PMID- 22404651
TI  - A triple arg motif mediates alpha(2B)-adrenergic receptor interaction with
      Sec24C/D and export.
AB  - Recent studies have demonstrated that cargo exit from the endoplasmic reticulum
      (ER) may be directed by ER export motifs recognized by components of the coat
      protein II (COPII) vesicles. However, little is known about ER export motifs and
      vesicle targeting of the G protein-coupled receptor (GPCR) superfamily. Here, we
      have demonstrated that a triple Arg (3R) motif in the third intracellular loop
      functions as a novel ER export signal for alpha(2B)-adrenergic receptor
      (alpha(2B)-AR). The 3R motif mediates alpha(2B)-AR interaction with Sec24C/D and
      modulates ER exit, cell surface transport and function of alpha(2B)-AR.
      Furthermore, export function of the 3R motif is independent of its position
      within alpha(2B)-AR and can be conferred to CD8 glycoprotein. These data provide
      the first evidence implicating that export of GPCRs is controlled by code
      directed interactions with selective components of the COPII transport machinery.

PMID- 22404655
TI  - Organofluorine chemistry: synthesis and conformation of vicinal fluoromethylene
      motifs.
AB  - The C-F bond is the most polar bond in organic chemistry, and thus the bond has a
      relatively large dipole moment with a significant -ve charge density on the
      fluorine atom and correspondingly a +ve charge density on carbon. The
      electrostatic nature of the bond renders it the strongest one in organic
      chemistry. However, the fluorine atom itself is nonpolarizable, and thus, despite
      the charge localization on fluorine, it is a poor hydrogen-bonding acceptor.
      These properties of the C-F bond make it attractive in the design of nonviscous
      but polar organic compounds, with a polarity limited to influencing the
      intramolecular nature of the molecule and less so intermolecular interactions
      with the immediate environment. In this Perspective, the synthesis of aliphatic
      chains carrying multivicinal fluoromethylene motifs is described. It emerges that
      the dipoles of adjacent C-F bonds orientate relative to each other, and thus,
      individual diastereoisomers display different backbone carbon chain
      conformations. These conformational preferences recognize the influence of the
      well-known gauche effect associated with 1,2-difluoroethane but extend to
      considering 1,3-fluorine-fluorine dipolar repulsions. The synthesis of carbon
      chains carrying two, three, four, five, and six vicinal fluoromethylene motifs is
      described, with an emphasis on our own research contributions. These motifs obey
      almost predictable conformational behavior, and they emerge as candidates for
      inclusion in the design of performance organic molecules.

PMID- 22404656
TI  - FGFR2 is associated with bipolar disorder: a large-scale case-control study of
      three psychiatric disorders in the Chinese Han population.
AB  - OBJECTIVES: Repetitive linkage analyses have indicated 10q25-q26 as a shared risk
      region for schizophrenia (SCZ) and bipolar disorder (BPD). A genome-wide
      association study and follow-up recently identified a significant association
      between a single nucleotide polymorphism (SNP) of this region (rs17101921) and
      SCZ. The nearest gene to this SNP is fibroblast growth factor receptor 2 (FGFR2).
      METHODS: We carried out a large scale case-control study to test the association
      between FGFR2 and three major psychiatric disorders: SCZ, BPD and major
      depressive disorder (MDD) in the Chinese Han population. Eight tag SNPs were
      genotyped using Taqman assay in 1139 BPD patients, 1112 SCZ patients, 1119 MDD
      patients and 1135 shared healthy controls. RESULTS: After correcting the multiple
      tests by permutation, one SNP (rs11199993), and a haplotype including this SNP,
      was found to be significantly associated with BPD. Potential population
      stratification in our samples was analyzed using 70 additional random SNPs
      dispersed on different chromosomes. No population stratification was detected, so
      our results could not be affected by this cofounding factor. Limitations of our
      study include incomplete coverage and insufficient power to detect association
      for relatively small odds ratio. CONCLUSIONS: Association between FGFR2 and BPD
      is worthy of further confirmation.

PMID- 22404657
TI  - Serotonin 2c receptor RNA editing in major depression and suicide.
AB  - OBJECTIVES: mRNA for serotonin 2C receptor (5-HT(2C)R) undergoes editing which
      results in numerous isoforms. More highly edited isoforms exhibit decreased
      function. We recently found greater 5-HT(2C)R editing in suicide victims with
      prior bipolar disorder (BPD) or schizophrenia (SZ) compared with non-suicide
      patients and normal controls (NC). This study compares suicides and non-suicides
      with major depressive disorder (MDD(Suic) and MDD(NoSuic)) and non-suicide NC.
      METHODS: mRNA editing was assessed in prefrontal cortex of 24 MDD(Suic), 21
      MDD(NoSuic), and 56 NC using next generation sequencing. mRNA expression of 5
      HT(2C)R and editing enzymes (ADAR1-2) was assessed by real-time PCR. RESULTS:
      Editing was lower in MDD(NoSuic) than in MDD(Suic), which did not differ from NC.
      No differences in the 5-HT(2C)R or ADAR1 expression were detected. ADAR2
      expression was higher in NC than in MDD subjects, but did not differ between
      MDD(NoSuic) and MDD(Suic). CONCLUSIONS: Our findings suggest the presence of two
      factors associated with 5-HT(2C)R editing. One factor, which probably stems from
      decreased ADAR2 expression, is linked to MDD and is associated with less editing.
      The other, seen also in our previous study of suicide in BP and SZ, is linked to
      suicide alone and is associated with more editing and, therefore, less receptor
      function.

PMID- 22404658
TI  - Molecular genetic overlap in bipolar disorder, schizophrenia, and major
      depressive disorder.
AB  - OBJECTIVES: Genome-wide association studies (GWAS) in complex phenotypes,
      including psychiatric disorders, have yielded many replicated findings, yet
      individual markers account for only a small fraction of the inherited differences
      in risk. We tested the performance of polygenic models in discriminating between
      cases and healthy controls and among cases with distinct psychiatric diagnoses.
      METHODS: GWAS results in bipolar disorder (BD), major depressive disorder (MDD),
      schizophrenia (SZ), and Parkinson's disease (PD) were used to assign weights to
      individual alleles, based on odds ratios. These weights were used to calculate
      allele scores for individual cases and controls in independent samples, summing
      across many single nucleotide polymorphisms (SNPs). How well allele scores
      discriminated between cases and controls and between cases with different
      disorders was tested by logistic regression. RESULTS: Large sets of SNPs were
      needed to achieve even modest discrimination between cases and controls. The most
      informative SNPs were overlapping in BD, SZ, and MDD, with correlated effect
      sizes. Little or no overlap was seen between allele scores for psychiatric
      disorders and those for PD. CONCLUSIONS: BD, SZ, and MDD all share a similar
      polygenic component, but the polygenic models tested lack discriminative accuracy
      and are unlikely to be useful for clinical diagnosis.

PMID- 22404659
TI  - FoxP2 is significantly associated with schizophrenia and major depression in the
      Chinese Han population.
AB  - OBJECTIVES: The FoxP2 gene, located on 7q31, encodes a transcription factor. It
      was first discovered through investigations of a large multigenerational family
      (the KE family) with a rare severe speech and language disorder (Fisher et al.,
      Nat. Genet. 1998;18:168; Lai et al., Nature 2001;413:519). Subsequent studies
      gave powerful and convincing functional evidence to the connection between FoxP2
      and language disorder ( Vernes et al. 2006 ; Groszer et al., Curr Biol
      2008;18:354; Vernes et al., New Engl J Med 359(22):2337). Language disorder is
      commonly considered as a core symptom of schizophrenia and some other mental
      diseases; thus, we decided to investigate whether the FoxP2 gene played a
      significant role in schizophrenia, major depression or bipolar disorder in a
      sample set recruited from the Chinese Han population. METHODS: In this study, we
      focused on 12 SNPs in the FoxP2 gene and carried out case-control studies in 1135
      schizophrenia patients, 1135 unrelated major depression patients, 1135 unrelated
      bipolar disorder patients and 1135 unrelated normal controls recruited from the
      Chinese Han population. RESULTS: We found rs10447760 was significantly associated
      with schizophrenia (allelic P = 0.00069) and major depression (allelic P =
      0.0011). CONCLUSIONS: Our study indicated that the rare variant rs10447760 in
      FoxP2 may play an important role in schizophrenia and major depression in the
      Chinese Han population.

PMID- 22404660
TI  - Neuropeptide S receptor gene (NPSR) and life events: G * E effects on anxiety
      sensitivity and its subdimensions.
AB  - OBJECTIVES: The pathogenesis of anxiety is assumed to be interactively influenced
      by genetic and environmental factors. Thus, a gene-environment interaction (G *
      E) study of the neuropeptide S receptor gene (NPSR) A/T polymorphism (rs324981)
      and life events was conducted with respect to anxiety sensitivity (AS) as an
      intermediate phenotype of anxiety disorders. METHODS: A sample of 475 healthy
      German subjects was genotyped for NPSR and assessed for AS, childhood
      maltreatment (CTQ) and recent life events (LTE). Influences on AS and its
      subdimensions were determined by a step-wise hierarchical regression and a
      multiple indicator multiple cause (MIMIC) model. RESULTS: Significant main
      effects of NPSR and CTQ as well as significant G * E were observed, with T/T
      homozygosity and a high CTQ score resulting in increased anxiety sensitivity.
      MIMIC modelling yielded association of AS subfactor "concern about
      mental/cognitive incapacitation" and the basal somatic subdimension "concern
      about physical sensations" to be associated with CTQ and its interaction with
      NPSR, while the acute somatic subfactor "concern about heart/lung failure" was
      associated with NPSR and its interaction with LTE. CONCLUSIONS: Results indicate
      G * E effects of the more active NPSR rs324981 T allele and life events on AS
      with differential effects of temporally proximal and distal factors on specific
      AS subdimensions.

PMID- 22404661
TI  - Candidate system analysis in ADHD: evaluation of nine genes involved in
      dopaminergic neurotransmission identifies association with DRD1.
AB  - OBJECTIVES: Several pharmacological and genetic studies support the involvement
      of the dopamine neurotransmitter system in the aetiology of attention-deficit
      hyperactivity disorder (ADHD). Based on this information we evaluated the
      contribution to ADHD of nine genes involved in dopaminergic neurotransmission
      (DRD1, DRD2, DRD3, DRD4, DRD5, DAT1, TH, DBH and COMT). METHODS: We genotyped a
      total of 61 tagging single nucleotide polymorphisms (SNPs) in a sample of 533
      ADHD patients (322 children and 211 adults), 533 sex-matched unrelated controls
      and additional 196 nuclear ADHD families from Spain. RESULTS: The single- and
      multiple-marker analysis in both population and family-based approaches provided
      preliminary evidence for the contribution of DRD1 to combined-type ADHD in
      children (P=8.8e-04; OR=1.50 (1.18-1.90) and P=0.0061; OR=1.73 (1.23-2.45)) but
      not in adults. Subsequently, we tested positive results for replication in an
      independent sample of 353 German families with combined-type ADHD children and
      replicated the initial association between DRD1 and childhood ADHD (P=8.4e-05;
      OR=3.67 (2.04-6.63)). CONCLUSIONS: The replication of the association between
      DRD1 and ADHD in two European cohorts highlights the validity of our finding and
      supports the involvement of DRD1 in childhood ADHD.

PMID- 22404662
TI  - Medial prefrontal dysfunction and prolonged amygdala response during instructed
      fear processing in borderline personality disorder.
AB  - OBJECTIVES: Affective dysregulation is a clinical hallmark of borderline
      personality disorder (BPD). This study used an instructed fear task combined with
      functional MRI (fMRI) and skin conductance response (SCR) to test hypotheses
      about mechanisms of disturbed fronto-limbic neural circuitry underlying
      dysfunctional emotional processing in BPD. METHODS: Female BPD patients and
      matched control subjects were exposed to two visual stimuli during fMRI scanning
      and SCR recording. Subjects were instructed shortly before scanning that one
      stimulus (Threat) potentially represents an aversive event whereas another
      stimulus (Safe) represents safety. The aversive event (electrodermal stimulation)
      itself was only experienced before this instruction and never occurred during
      fMRI scanning. RESULTS: Both groups showed stronger SCR to Threat compared to
      Safe indicating differential fear response which habituated over time. BPD
      compared to control subjects did not show fMRI signal decrease of amygdala
      activity or relative ventromedial prefrontal cortex (vmPFC) activity increase
      over time. Moreover, BPD patients showed increased connectivity of the amygdala
      with vmPFC but decreased connectivity of subgenual ACC with dorsal ACC compared
      to control subjects. CONCLUSIONS: Prolonged amygdala response and a functional
      disconnection between ventral and dorsal mPFC regions may be part of the neural
      mechanisms underlying emotional dysregulation in BPD patients.

PMID- 22404663
TI  - Pharmacotherapy of the third-generation AEDs: lacosamide, retigabine and
      eslicarbazepine acetate.
AB  - INTRODUCTION: The search for new, more effective antiepileptic drugs (AEDs)
      continues. The three most recently approved drugs, the so-called third-generation
      AEDs, include lacosamide, retigabine and eslicarbazepine acetate and are licensed
      as adjunctive treatment of partial epilepsy in adults. AREAS COVERED: For the
      above three AEDs, their mechanisms of action, pharmacokinetic characteristics,
      drug-drug interactions, pharmacotherapeutics, dose and administration and
      therapeutic drug monitoring are reviewed in this paper. EXPERT OPINION:
      Lacosamide and retigabine act through novel mechanisms, while eslicarbazepine
      acetate, a pro-drug for eslicarbazepine, acts in a similar manner to several
      other AEDs. All three AEDs are associated with linear pharmacokinetic and rapid
      absorption and undergo metabolism. Their drug-drug interaction profile is low
      (lacosamide and retigabine) to modest (eslicarbazepine) in propensity. At the
      highest approved doses for the three AEDs, responder rates were similar. The most
      commonly observed adverse effects compared with placebo were dizziness, headache,
      diplopia and nausea for lacosamide; dizziness, somnolence and fatigue for
      retigabine and dizziness and somnolence for eslicarbazepine acetate. The precise
      role that these new AEDs will have in the treatment of epilepsy and whether they
      will make a significant impact on the prognosis of intractable epilepsy is not
      yet known and will have to await further clinical experience.

PMID- 22404664
TI  - Comparison between a bovine and a human enterohaemorrhagic Escherichia coli
      strain of serogroup O26 by suppressive subtractive hybridization reveals the
      presence of atypical factors in EHEC and EPEC strains.
AB  - Enterohaemorrhagic Escherichia coli (EHEC) strains are responsible for food
      poisoning in humans in developed countries via consumption of vegetal and animal
      foodstuffs contaminated by ruminant feces. The clinical conditions caused by EHEC
      strains vary from undifferentiated diarrhea to hemorrhagic colitis with, in a few
      cases, the appearance of the hemolytic uremic syndrome, which can lead to death.
      Most EHEC strains can be found in the gut of healthy ruminants, but some of the
      strains, belonging to O26, O111, O118 serogroups, for example, are also
      responsible for digestive disorders in calves. The aim of this research was to
      study the genomic differences between two EHEC strains of serogroup O26 isolated
      from a young calf and a human with diarrhea, to identify specific sequences of
      the bovine strain that could be implicated in initial adherence or host
      specificity. No sequence implicated in host specificity was found during our
      study. Finally, several factors, not usually present in EHEC strains of serogroup
      O26, were identified in the bovine strain. One of them, the PAI I(CL3)  locus
      initially presented as a marker for LEE-negative VTEC strains, was found in 11.3%
      of EPEC and EHEC strains.

PMID- 22404665
TI  - Influence of liver-disease etiology on long-term quality of life and employment
      after liver transplantation.
AB  - The etiology of liver disease would expectedly affect health-related quality of
      life (HRQoL) and employment after liver transplantation (LT), but studies are
      scarce. We sent the 15D HRQoL instrument and an employment questionnaire to all
      401 adult LT patients alive in Finland in 2007. The response rate was 89% (n =
      353; mean of eight yr since LT). In age-adjusted analysis, patients transplanted
      for primary sclerosing cholangitis (PSC; n = 56), primary biliary cirrhosis (PBC;
      n = 72), acute liver failure (ALF; n = 76), alcoholic cirrhosis (n = 38), or
      liver tumor (n = 22) exhibited comparable HRQoL, whereas the combined group of
      miscellaneous chronic liver diseases (n = 89) exhibited significantly higher
      HRQoL scores (p = 0.003). Among working-aged patients (20-65 yr at LT),
      employment rates were highest in the PSC (56%) group and lowest in the ALF (39%)
      and PBC (29%) groups. In age-adjusted logistic regression, patients with PSC or
      alcoholic cirrhotics were 2.4- and 2.5-fold more likely to resume work after LT
      than patients with PBC. In conclusion, HRQoL scores late after LT were in general
      relatively high and comparable among disease groups. Patients with PSC or
      alcoholic cirrhosis were most likely to resume work after LT. The relatively low
      employment among patients with ALF may merit enhanced rehabilitation efforts.

PMID- 22404666
TI  - Melatonin inhibits matrix metalloproteinase-9 (MMP-9) activation in the
      lipopolysaccharide (LPS)-stimulated RAW 264.7 and BV2 cells and a mouse model of
      meningitis.
AB  - We explored anti-inflammatory potential of melatonin against the
      lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro. RAW 264.7 and
      BV2 cells were stimulated by LPS, followed by the treatment with melatonin or
      vehicle at various time intervals. In a mouse model of meningitis induced by LPS,
      melatonin (5mg/kg) or vehicle was intravenously injected at 30min postinsult. The
      activity of matrix metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9)
      was determined by gelatin zymography. Nuclear factor-kappa B (NFkappaB)
      translocation and binding activity were determined by immunocytochemistry and
      electrophoretic mobility shift assay (EMSA). Our results showed that either
      pretreatment or cotreatment with melatonin at 50-500 MUm effectively inhibited
      the LPS-induced proMMP-9 activation in the RAW 264.7 and BV2 cells, respectively
      (P<0.05). This melatonin-induced proMMP-9 inhibition remained effective when
      treatment was delayed up to 2 and 6hr postinsult for RAW 264.7 and BV2 cells,
      respectively (P<0.05 for both groups). Additionally, melatonin significantly
      attenuated the rises of circulatory and cerebral MMP-9 activity, respectively
      (P<0.05) and reduced the loss of body weight (P<0.05) in mice with meningitis.
      Moreover, melatonin (50MUm) effectively inhibited nuclear factor-kappa B
      (NFkappaB) translocation and binding activity in the LPS-treated RAW 264.7 and
      BV2 cells, respectively (P<0.05). These results demonstrate direct inhibitory
      actions of melatonin against postinflammatory NFkappaB translocation and MMP-9
      activation and highlight its ability to inhibit systemic and cerebral MMP-9
      activation following brain inflammation.

PMID- 22404667
TI  - Frameless robotically targeted stereotactic brain biopsy: feasibility, diagnostic
      yield, and safety.
AB  - OBJECT: Frameless stereotactic brain biopsy has become an established procedure
      in many neurosurgical centers worldwide. Robotic modifications of image-guided
      frameless stereotaxy hold promise for making these procedures safer, more
      effective, and more efficient. The authors hypothesized that robotic brain biopsy
      is a safe, accurate procedure, with a high diagnostic yield and a safety profile
      comparable to other stereotactic biopsy methods. METHODS: This retrospective
      study included 41 patients undergoing frameless stereotactic brain biopsy of
      lesions (mean size 2.9 cm) for diagnostic purposes. All patients underwent image
      guided, robotic biopsy in which the SurgiScope system was used in conjunction
      with scalp fiducial markers and a preoperatively selected target and trajectory.
      Forty-five procedures, with 50 supratentorial targets selected, were performed.
      RESULTS: The mean operative time was 44.6 minutes for the robotic biopsy
      procedures. This decreased over the second half of the study by 37%, from 54.7 to
      34.5 minutes (p < 0.025). The diagnostic yield was 97.8% per procedure, with a
      second procedure being diagnostic in the single nondiagnostic case. Complications
      included one transient worsening of a preexisting deficit (2%) and another
      deficit that was permanent (2%). There were no infections. CONCLUSIONS: Robotic
      biopsy involving a preselected target and trajectory is safe, accurate,
      efficient, and comparable to other procedures employing either frame-based
      stereotaxy or frameless, nonrobotic stereotaxy. It permits biopsy in all
      patients, including those with small target lesions. Robotic biopsy planning
      facilitates careful preoperative study and optimization of needle trajectory to
      avoid sulcal vessels, bridging veins, and ventricular penetration.

PMID- 22404668
TI  - Acute postoperative neurological deterioration associated with surgery for
      ruptured intracranial aneurysm: incidence, predictors, and outcomes.
AB  - OBJECT: Subarachnoid hemorrhage (SAH) results in significant morbidity and
      mortality, even among patients who reach medical attention in good neurological
      condition. Many patients have neurological decline in the perioperative period,
      which contributes to long-term outcomes. The focus of this study is to
      characterize the incidence of, characteristics predictive of, and outcomes
      associated with acute postoperative neurological deterioration in patients
      undergoing surgery for ruptured intracranial aneurysm. METHODS: The
      Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) was a multicenter
      randomized clinical trial that enrolled 1001 patients and assesssed the efficacy
      of hypothermia as neuroprotection during surgery to secure a ruptured
      intracranial aneurysm. All patients had a radiographically confirmed SAH, were
      classified as World Federation of Neurosurgical Societies (WFNS) Grade I-III
      immediately prior to surgery, and underwent surgery to secure the ruptured
      aneurysm within 14 days of SAH. Neurological assessment with the National
      Institutes of Health Stroke Scale (NIHSS) was performed preoperatively, at 24 and
      72 hours postoperatively, and at time of discharge. The primary outcome variable
      was a dichotomized scoring based on an IHAST version of the Glasgow Outcome Scale
      (GOS) in which a score of 1 represents a good outcome and a score > 1 a poor
      outcome, as assessed at 90-days' follow-up. Data from IHAST were analyzed for
      occurrence of a postoperative neurological deterioration. Preoperative and
      intraoperative variables were assessed for associations with occurrence of
      postoperative neurological deterioration. Differences in baseline,
      intraoperative, and postoperative variables and in outcomes between patients with
      and without postoperative neurological deterioration were compared with Fisher
      exact tests. The Wilcoxon rank-sum test was used to compare variables reported as
      means. Multiple logistic regression was used to adjust for covariates associated
      with occurrence of postoperative deficit. RESULTS: Acute postoperative
      neurological deterioration was observed in 42.6% of the patients. New focal motor
      deficit accounted for 65% of postoperative neurological deterioration, while 60%
      was accounted for using the NIHSS total score change and 51% by Glasgow Coma
      Scale score change. Factors significantly associated with occurrence of
      postoperative neurological deterioration included: age, Fisher grade on
      admission, occurrence of a procedure prior to aneurysm surgery (ventriculostomy),
      timing of surgery, systolic blood pressure during surgery, ST segment depression
      during surgery, history of abnormality in cardiac valve function, use of
      intentional hypotension during surgery, duration of anterior cerebral artery
      occlusion, intraoperative blood loss, and difficulty of aneurysm exposure. Of the
      426 patients with postoperative neurological deterioration at 24 hours after
      surgery, only 46.2% had a good outcome (GOS score of 1) at 3 months, while 77.7%
      of those without postoperative neurological deterioration at 24 hours had a good
      outcome (p < 0.05). CONCLUSIONS: Neurological injury incurred perioperatively or
      in the acute postoperative period accounts for a large percentage of poor
      outcomes in patients with good admission WFNS grades undergoing surgery for
      aneurysmal SAH. Avoiding surgical factors associated with postoperative
      neurological deterioration and directing investigative efforts at developing
      improved neuroprotection for use in aneurysm surgery may significantly improve
      long-term neurological outcomes in patients with SAH.

PMID- 22404669
TI  - Endoscopic balloon dilation as an adjunct to extended endoscopic approaches to
      the skull base.
AB  - Cholesterol granulomas (CGs) are benign, expanding cystic lesions surrounded by a
      thick fibrous capsule and filled with fluid, formed by the degradation of blood
      elements. The goal of surgery is to open the granuloma widely, creating a well
      drained cavity. The endonasal endoscopic approach for this extradural lesion is a
      minimal access method for surgical removal or fenestration. The role of balloon
      dilation in creating a wide fenestration has not been previously described.   The
      authors describe a patient with a recurrent petrous apex CG who underwent an
      endoscopic, endonasal, transmaxillary transpterygoid approach to the petrous
      apex. A balloon sinuplasty catheter was used to dilate the surgical fenestration
      to maintain continued patency.   The authors report on their first experience
      using balloon dilation combined with endoscopic drainage of the petrous apex. The
      excellent surgical outcome of this minimally invasive technique holds promise for
      future endonasal approaches to the middle cranial fossa.

PMID- 22404670
TI  - Management of glioblastoma multiforme in pregnancy.
AB  - Glioblastoma multiforme presenting during pregnancy presents unique challenges to
      the clinician. In planning treatment, potential benefits to the mother must be
      balanced against the risks to the fetus. In addition, evidence relating to timing
      of surgery and the use of radiotherapy and chemotherapy in pregnancy is limited.
      Management of peritumoral edema and seizures in pregnancy is also complicated by
      the potential for drug-related teratogenic effects and adverse neonatal outcomes
      on the fetus. The general anesthetic used for surgery must factor obstetric and
      neurosurgical considerations.   In this review article, the authors seek to
      examine the role, safety, and timing of therapies for glioblastoma in the context
      of pregnancy. This covers the use of radiotherapy and chemotherapy, timing of
      surgery, postoperative care, anesthetic considerations, and use of anticonvulsant
      medications and steroids. The authors hope that this will provide a framework for
      clinicians treating pregnant patients with glioblastomas.

PMID- 22404671
TI  - Management of device-related wound complications in deep brain stimulation
      surgery.
AB  - OBJECT: Wound complications are uncommon following deep brain stimulation (DBS)
      surgery. However, certain key technical steps can be performed in each procedure
      to minimize this still troublesome risk. The authors reviewed the incidence and
      management of all hardware-related wound dehiscences and infections in a large
      patient series. METHODS: All patients undergoing new DBS hardware implantation
      surgery between 2002 and 2010 by a single surgeon (R.K.S.) were entered into a
      database after undergoing verification by cross-referencing manufacturer
      implantation records. All hardware-related complications such as wound
      dehiscence, erosions, and/or infections were identified, and wound location, time
      of incidence, and mechanism were categorized. Charts were reviewed to evaluate
      the success of conservative treatment versus partial or total hardware removal.
      RESULTS: Seven hundred twenty-eight patients received 1333 new DBS leads and 1218
      new implantable pulse generators (IPGs) in a total of 1356 stereotactic
      procedures for movement disorders. Seventy-eight percent of patients underwent
      staged lead and IPG implantations. Sixteen patients presented with atraumatic
      device-related infection and/or dehiscence within 12 months from original
      implantation; 9 of these patients (1.24%) required additional surgery after
      antibiotic failure. All 8 patients presenting with cranial wound complications
      were treated initially by debridement in an attempt to salvage the leads;
      debridement followed by intravenous antibiotics was only successful in 2 patients
      presenting with dehiscence alone. One of 2 lead-only removals was successful in
      infections originating in the cranium; the only IPG-originating infection was
      treated by partial hardware removal and intravenous antibiotics. Two of 637 IPG
      replacements resulted in infections within 12 months after revision, requiring
      either partial or total hardware removal, while 1 dehiscence in this group was
      treated by debridement alone. CONCLUSIONS: In a large series of new DBS hardware
      implantations, the incidence of postoperative wound dehiscence and/or infections
      requiring further surgery was 1.24%. Standard practice for all implantations was
      a short procedural duration, copious povidone-iodine irrigation, and
      postoperative antibiotic administration. Partial hardware removal should be
      initially attempted for infection. Debridement alone is successful in treating
      dehiscence without infection.

PMID- 22404672
TI  - Optimal entry point and trajectory for endoscopic third ventriculostomy:
      evaluation of 53 patients with volumetric imaging guidance.
AB  - OBJECT: An optimal entry point for endoscopic third ventriculostomy (ETV) helps
      protect critical structures from undue manipulation. A commonly accepted ideal
      entry point is 3 cm from the midline and 1 cm anterior to the coronal suture. The
      authors of this study reexamine this ideal entry point. METHODS: Trajectory views
      from MR images or CT scans used for cranial image guidance in 53 patients (age
      range 3-85 years) who had undergone ETV were retrospectively evaluated. The
      trajectory from the tuber cinereum back through the center of the foramen of
      Monro was projected to the surface of the head. The relation of the entry point
      to the midline and the coronal suture was established. RESULTS: The mean
      perpendicular distance from the ideal entry point to the midline was 30.1 +/- 7
      mm (median 31.9 mm, range 12.5-42.2 mm). The mean perpendicular distance to the
      coronal suture was 8.9 +/- 14.1 mm posterior (median 10.4 mm), ranging from 30.6
      mm anterior to 35.8 mm posterior. The entry point tended to be located more
      posteriorly in women and adults: 5.8 +/- 15.4 mm posterior in males versus 13.1
      +/- 13.2 mm posterior in females (p = 0.08) and 9.1 +/- 14.8 mm posterior in
      adults versus 8.2 +/- 11.7 mm posterior in children (p = 0.84). CONCLUSIONS:
      While the entry point may need to be modified from the ideal trajectory for other
      anatomical reasons, such as a trajectory through the motor cortex, in general,
      the authors found that the optimal entry point for ETV was more posterior than
      previously published and highly variable. Using image guidance or a customized
      trajectory based on analysis of a patient's own imaging is highly preferable to
      using an empirical ideal trajectory.

PMID- 22404673
TI  - Panacea or problem: flow diverters in the treatment of symptomatic large or giant
      fusiform vertebrobasilar aneurysms.
AB  - OBJECT: The use of flow-diverting stents has gained momentum as a curative
      approach in the treatment of complex proximal anterior circulation intracranial
      aneurysms. There have been some reported attempts of treating formidable lesions
      in the posterior circulation. Posterior circulation giant fusiform aneurysms have
      a particularly aggressive natural history. To date, no one approach has been
      shown to be comprehensively effective or low risk. The authors report the initial
      results, including the significant morbidity and mortality encountered, with flow
      diversion in the treatment of large or giant fusiform vertebrobasilar aneurysms
      at Millard Fillmore Gates Circle Hospital. METHODS: The authors retrospectively
      reviewed their prospectively collected endovascular database to identify patients
      with intracranial aneurysms who underwent treatment with flow-diverting devices
      and determined that 7 patients had presented with symptomatic large or giant
      fusiform vertebrobasilar aneurysms. The outcomes of these patients, based on the
      modified Rankin Scale (mRS), were tabulated, as were the complications
      experienced. RESULTS: Among the 7 patients, Pipeline devices were placed in 6
      patients and Silk devices in 1 patient. At the last follow-up evaluation, 4
      patients had died (mRS score of 6), all of whom were treated with the Pipeline
      device. The other 3 patients had mRS scores of 5 (severe disability), 1, and 0.
      The deaths included posttreatment aneurysm ruptures in 2 patients and lack of
      improvement in neurological status related to presenting brainstem infarcts and
      subsequent withdrawal of care in the other 2 patients. CONCLUSIONS: Whether flow
      diversion will be an effective strategy for treatment of large or giant fusiform
      vertebrobasilar aneurysms remains to be seen. The authors' initial experience
      suggests substantial morbidity and mortality associated with the treatment and
      with the natural history. As outcomes data slowly become available for patients
      receiving these devices for fusiform posterior circulation aneurysms,
      practitioners should use these devices judiciously.

PMID- 22404674
TI  - Mirror aneurysms.

PMID- 22404675
TI  - Mirror aneurysms: a reflection on natural history.
AB  - OBJECT: Investigators conducting the International Study of Unruptured
      Intracranial Aneurysms, sponsored by the National Institutes of Health, sought to
      evaluate predictors of future hemorrhage in patients who had unruptured mirror
      aneurysms. These paired aneurysms in bilateral arterial positions mirror each
      other; their natural history is unknown. METHODS: Centers in the US, Canada, and
      Europe enrolled patients for prospective assessment of unruptured intracranial
      aneurysms. Central radiological review confirmed the presence or absence of
      mirror aneurysms in patients without a history of prior subarachnoid hemorrhage
      (SAH) (Group 1). Outcome at 1 and 5 years and aneurysm characteristics are
      compared. RESULTS: Of 3120 patients with aneurysms treated in 61 centers, 376
      (12%) had mirror aneurysms, which are more common in women than men (82% [n =
      308] vs 73% [n = 1992], respectively; p <0.001) and in patients with a family
      history of aneurysm or SAH (p <0.001). Compared with patients with nonmirror
      saccular aneurysms, a greater percentage of patients with mirror aneurysms had
      larger (>10 mm) aneurysms (mean maximum diameter 11.7 vs 10.4 mm, respectively; p
      <0.001). The most common distribution for mirror aneurysms was the middle
      cerebral artery (34% [126 patients]) followed by noncavernous internal carotid
      artery (32% [121]), posterior communicating artery (16% [60]), cavernous internal
      carotid artery (13% [48]), anterior cerebral artery/anterior communicating artery
      (3% [13]), and vertebrobasilar circulation (2% [8]). When these patients were
      compared with patients without mirror aneurysms, no statistically significant
      differences were found in age (mean age 54 years in both groups), blood pressure,
      smoking history, or cardiac disease. Aneurysm rupture rates were similar (3.0%
      for patients with mirror aneurysms vs 2.8% for those without). CONCLUSIONS:
      Overall, patients with mirror aneurysms were more likely to be women, to report a
      family history of aneurysmal SAH, and to have larger aneurysms. The presence of a
      mirror aneurysm was not an independent predictor of future SAHs.

PMID- 22404676
TI  - Intractable epilepsy in paralimbic Word Health Organization Grade II gliomas:
      should the hippocampus be resected when not invaded by the tumor?
AB  - OBJECT: Beyond its oncological benefit, surgery could improve seizure control in
      paralimbic frontotemporoinsular or temporoinsular WHO Grade II gliomas generating
      intractable seizures. However, no studies have examined the impact of hippocampal
      resection on chronic epilepsy when the hippocampus is not invaded by Grade II
      gliomas. Here, the authors compared the epileptological outcomes and return to
      work in 2 groups of patients who underwent surgery with or without
      hippocampectomy for paralimbic Grade II gliomas eliciting intractable epilepsy
      despite no tumoral involvement of the hippocampus. METHODS: Surgery was performed
      in 15 consecutive patients who were unable to work (median Karnofsky Performance
      Scale [KPS] Score 70) because of refractory epilepsy due to paralimbic Grade II
      gliomas that were not invading the hippocampus. In Group A (8 patients), the
      hippocampus was preserved. In Group B (7 patients), glioma removal was associated
      with hippocampectomy. RESULTS: No patient died or suffered a permanent deficit
      after surgery. Postoperatively, in Group A, no patients were seizure free (4
      patients were in Engel Class II and 4 were in Class III). In Group B, all 7
      patients were seizure free (Class I) (p = 0.02). Only 62.5% of patients returned
      to work in Group A, whereas all patients are working full time in Group B. The
      postsurgical median KPS score was 85 in Group A, that is, not significantly
      improved in comparison with the preoperative score, while the postsurgical median
      KPS was 95 in Group B, that is, significantly improved in comparison with the
      preoperative score (p = 0.03). CONCLUSIONS: The authors' data support, for the
      first time, the significant impact of hippocampectomy in patients with
      intractable epilepsy generated by a paralimbic Grade II glioma, even if it does
      not invade the hippocampus. Hippocampal resection allowed seizure control in all
      patients, with an improvement in KPS scores, since all patients resumed their
      social and professional activities. Thus, the authors suggest performing a
      resection of the nontumoral hippocampus in addition to resection of the tumor in
      patients with refractory epilepsy due to paralimbic Grade II gliomas.

PMID- 22404677
TI  - Fatigue and heat sensitivity in patients with multiple sclerosis.
AB  - OBJECTIVES: Fatigue is one of the most common and troubling symptoms of multiple
      sclerosis (MS), and heat is often reported as a trigger. Although it is assumed
      that this heat sensitivity is specific for MS, the evidence for disease
      specificity is limited. We studied the relationship between fatigue, heat
      sensitivity, and environmental temperature, and its specificity for MS. MATERIALS
      AND METHODS: We compared 88 MS patients with 76 patients with ulcerative colitis
      (UC), another chronic auto-immune disease. As most important outcome measures,
      heat sensitivity, physical fatigue, mental fatigue, environmental temperature,
      and ambient UV-light levels were determined. RESULTS: More patients with MS
      reported heat sensitivity for fatigue, compared to patients with UC (53.4% vs
      35.5%, respectively, P = 0.016). However, heat-sensitive patients were equally
      fatigued as heat-insensitive patients. Climatological data, including day
      temperature and amount of ambient UV light, were not related to fatigue in both
      heat-sensitive and heat-insensitive patients with MS. CONCLUSIONS: Our findings
      support the assumption that heat sensitivity regarding fatigue has an MS-specific
      component. Although patients with MS experience a relationship between
      environmental temperature and fatigue, objective assessment by climatological
      data could not confirm this.

PMID- 22404678
TI  - Virus maturation.
AB  - We examine virus maturation of selected nonenveloped and enveloped single
      stranded RNA viruses, retroviruses, bacteriophages, and herpesviruses. Processes
      associated with maturation in the RNA viruses range from subtle (nodaviruses and
      picornaviruses) to dramatic (tetraviruses and togaviruses). The elaborate
      assembly and maturation pathway of HIV is discussed in contrast to the less
      sophisticated but highly efficient processes associated with togaviruses.
      Bacteriophage assembly and maturation are discussed in general terms, with
      specific examples chosen for emphasis. Finally the herpesviruses are compared
      with bacteriophages. The data support divergent evolution of nodaviruses,
      picornaviruses, and tetraviruses from a common ancestor and divergent evolution
      of alphaviruses and flaviviruses from a common ancestor. Likewise, bacteriophages
      and herpesviruses almost certainly share a common ancestor in their evolution.
      Comparing all the viruses, we conclude that maturation is a convergent process
      that is required to solve conflicting requirements in biological dynamics and
      function.

PMID- 22404679
TI  - Receptor signaling clusters in the immune synapse.
AB  - Signaling processes between various immune cells involve large-scale spatial
      reorganization of receptors and signaling molecules within the cell-cell
      junction. These structures, now collectively referred to as immune synapses,
      interleave physical and mechanical processes with the cascades of chemical
      reactions that constitute signal transduction systems. Molecular level
      clustering, spatial exclusion, and long-range directed transport are all emerging
      as key regulatory mechanisms. The study of these processes is drawing researchers
      from physical sciences to join the effort and represents a rapidly growing branch
      of biophysical chemistry. Recent advances in physical and quantitative analyses
      of signaling within the immune synapses are reviewed here.

PMID- 22404681
TI  - Bacterial mechanosensitive channels--MscS: evolution's solution to creating
      sensitivity in function.
AB  - The discovery of mechanosensing channels has changed our understanding of
      bacterial physiology. The mechanosensitive channel of small conductance (MscS) is
      perhaps the most intensively studied of these channels. MscS has at least two
      states: closed, which does not allow solutes to exit the cytoplasm, and open,
      which allows rapid efflux of solvent and solutes. The ability to appropriately
      open or close the channel (gating) is critical to bacterial survival. We briefly
      review the science that led to the isolation and identification of MscS. We
      concentrate on the structure-function relationship of the channel, in particular
      the structural and biochemical approaches to understanding channel gating. We
      highlight the troubling discrepancies between the various models developed to
      understand MscS gating.

PMID- 22404680
TI  - Forcing stem cells to behave: a biophysical perspective of the cellular
      microenvironment.
AB  - Physical factors in the local cellular microenvironment, including cell shape and
      geometry, matrix mechanics, external mechanical forces, and nanotopographical
      features of the extracellular matrix, can all have strong influences on
      regulating stem cell fate. Stem cells sense and respond to these insoluble
      biophysical signals through integrin-mediated adhesions and the force balance
      between intracellular cytoskeletal contractility and the resistant forces
      originated from the extracellular matrix. Importantly, these mechanotransduction
      processes can couple with many other potent growth-factor-mediated signaling
      pathways to regulate stem cell fate. Different bioengineering tools and
      microscale/nanoscale devices have been successfully developed to engineer the
      physical aspects of the cellular microenvironment for stem cells, and these tools
      and devices have proven extremely powerful for identifying the extrinsic physical
      factors and their downstream intracellular signaling pathways that control stem
      cell functions.

PMID- 22404682
TI  - Cooperativity in cellular biochemical processes: noise-enhanced sensitivity,
      fluctuating enzyme, bistability with nonlinear feedback, and other mechanisms for
      sigmoidal responses.
AB  - Cooperativity in classical biophysics originates from molecular interactions;
      nonlinear feedbacks in biochemical networks regulate dynamics inside cells. Using
      stochastic reaction kinetic theory, we discuss cooperative transitions in
      cellular biochemical processes at both the macromolecular and the cellular
      levels. We show that fluctuation-enhanced sensitivity (stochastic focusing)
      shares an essential feature with the transition in a bistable system. The same
      theory explains zeroth-order ultrasensitivity with temporal cooperativity.
      Dynamic cooperativity in fluctuating enzyme (i.e., dynamic disorder), stochastic
      focusing, and the recently proposed stochastic binary decision all have a shared
      mechanism: They are generalizations of the hyperbolic response of Michaelis
      Menten kinetics x/(K+x), with fluctuating K or stochastic x. Sigmoidal dependence
      on substrate concentration necessarily yields affinity amplification for
      competing ligands; both sigmoidal response and affinity amplification exhibit a
      square law. We suggest two important characteristics in a noise: its multimodal
      distribution structure and its temporal irreversibility. The former gives rise to
      self-organized complexity, and the latter contains useful, albeit hidden, free
      energy that can be utilized for biological functions. There could be structures
      and energy in biochemical fluctuations.

PMID- 22404685
TI  - Network-based models as tools hinting at nonevident protein functionality.
AB  - Network-based models of proteins are popular tools employed to determine dynamic
      features related to the folded structure. They encompass all topological and
      geometric computational approaches idealizing proteins as directly interacting
      nodes. Topology makes use of neighborhood information of residues, and geometry
      includes relative placement of neighbors. Coarse-grained approaches efficiently
      predict alternative conformations because of inherent collectivity in the protein
      structure. Such collectivity is moderated by topological characteristics that
      also tune neighborhood structure: That rich residues have richer neighbors
      secures robustness toward random loss of interactions/nodes due to environmental
      fluctuations/mutations. Geometry conveys the additional information of force
      balance to network models, establishing the local shape of the energy landscape.
      Here, residue and/or bond perturbations are critically evaluated to suggest new
      experiments, as network-based computational techniques prove useful in capturing
      domain movements and conformational shifts resulting from environmental
      alterations. Evolutionarily conserved residues are optimally connected, defining
      a subnetwork that may be utilized for further coarsening.

PMID- 22404683
TI  - Filamins in mechanosensing and signaling.
AB  - Filamins are essential, evolutionarily conserved, modular, multidomain, actin
      binding proteins that organize the actin cytoskeleton and maintain extracellular
      matrix connections by anchoring actin filaments to transmembrane receptors. By
      cross-linking and anchoring actin filaments, filamins stabilize the plasma
      membrane, provide cellular cortical rigidity, and contribute to the mechanical
      stability of the plasma membrane and the cell cortex. In addition to binding
      actin, filamins interact with more than 90 other binding partners including
      intracellular signaling molecules, receptors, ion channels, transcription
      factors, and cytoskeletal and adhesion proteins. Thus, filamins scaffold a wide
      range of signaling pathways and are implicated in the regulation of a diverse
      array of cellular functions including motility, maintenance of cell shape, and
      differentiation. Here, we review emerging structural and functional evidence that
      filamins are mechanosensors and/or mechanotransducers playing essential roles in
      helping cells detect and respond to physical forces in their local environment.

PMID- 22404686
TI  - ATP utilization and RNA conformational rearrangement by DEAD-box proteins.
AB  - RNA helicase enzymes catalyze the in vivo folding and conformational re
      arrangement of RNA. DEAD-box proteins (DBPs) make up the largest family of RNA
      helicases and are found across all phyla. DBPs are molecular motor proteins that
      utilize chemical energy in cycles of ATP binding, hydrolysis, and product release
      to perform mechanical work resulting in reorganization of cellular RNAs. DBPs
      contain a highly conserved motor domain helicase core. Auxiliary domains,
      enzymatic adaptations, and regulatory partner proteins contribute to the
      diversity of DBP function throughout RNA metabolism. In this review we focus on
      the current understanding of the DBP ATP utilization mechanism in rearranging and
      unwinding RNA structures. We discuss DBP structural properties, kinetic pathways,
      and thermodynamic features of nucleotide-dependent interactions with RNA. We
      highlight recent advances in the DBP field derived from biochemical and molecular
      biophysical investigations aimed at developing a quantitative mechanistic
      understanding of DBP molecular motor function.

PMID- 22404684
TI  - Single-molecule views of protein movement on single-stranded DNA.
AB  - The advent of new technologies allowing the study of single biological molecules
      continues to have a major impact on studies of interacting systems as well as
      enzyme reactions. These approaches (fluorescence, optical, and magnetic
      tweezers), in combination with ensemble methods, have been particularly useful
      for mechanistic studies of protein-nucleic acid interactions and enzymes that
      function on nucleic acids. We review progress in the use of single-molecule
      methods to observe and perturb the activities of proteins and enzymes that
      function on flexible single-stranded DNA. These include single-stranded DNA
      binding proteins, recombinases (RecA/Rad51), and helicases/translocases that
      operate as motor proteins and play central roles in genome maintenance. We
      emphasize methods that have been used to detect and study the movement of these
      proteins (both ATP-dependent directional and random movement) along the single
      stranded DNA and the mechanistic and functional information that can result from
      detailed analysis of such movement.

PMID- 22404688
TI  - Widespread fitness alignment in the legume-rhizobium symbiosis.
AB  - Although 'cheaters' potentially destabilize the legume-rhizobium mutualism, we
      lack a comprehensive review of host-symbiont fitness correlations. Studies
      measuring rhizobium relative or absolute fitness and host benefit are surveyed.
      Mutant studies are tallied for evidence of pleiotropy; studies of natural strains
      are analyzed with meta-analysis. Of 80 rhizobium mutations, 19 decrease both
      partners' fitness, four increase both, two increase host fitness but decrease
      symbiont fitness and none increase symbiont fitness at the host's expense. The
      pooled correlation between rhizobium nodulation competitiveness and plant
      aboveground biomass is 0.65 across five experiments that compete natural strains
      against a reference, whereas, across 14 experiments that compete rhizobia against
      soil populations or each other, the pooled correlation is 0.24. Pooled
      correlations between aboveground biomass and nodule number and nodule biomass are
      0.76 and 0.83. Positive correlations between legume and rhizobium fitness imply
      that most ineffective rhizobia are 'defective' rather than 'defectors'; this
      extends to natural variants, with only one significant fitness conflict. Most
      studies involve non-coevolved associations, indicating that fitness alignment is
      the default state. Rhizobium mutations that increase both host and symbiont
      fitness suggest that some plants maladaptively restrict symbiosis with novel
      strains.

PMID- 22404687
TI  - Are there new threshold and goals in the treatment of arterial hypertension?
AB  - BACKGROUND: About half of the global burden of cardiovascular disease has been
      attributed to high blood pressure (BP). Worldwide, 7.6 million premature deaths
      (about 13.5% of the global total), 54% of strokes, and 47% of cases of ischemic
      heart disease were caused by high BP in 2001. METHODS AND RESULTS: All guidelines
      agree that pharmacological treatment of patients with hypertension should be
      initiated as soon as BP rises >140/90 mmHg. Available data support the reduction
      of BP to values to <140/90 mmHg, but do not favor a reduction to <130/80 mmHg in
      patients with diabetes or a history of cardiovascular disease because of the
      absence of evidence obtained in prospective studies. CONCLUSIONS: This review
      updates the controversies and challenges involved in the treatment of patients
      with established arterial hypertension, such as the progression of high-normal BP
      to overt hypertension, the choice of appropriate threshold and goal BP levels,
      the adequate number of drugs to be used since the early stages of hypertension,
      and which type of combination therapy offers most advantages to the patient.

PMID- 22404689
TI  - Occurrence of trenbolone acetate metabolites in simulated confined animal feeding
      operation (CAFO) runoff.
AB  - Metabolites of androgenic synthetic growth promoters used at confined animal
      feeding operations (CAFOs) pose a demonstrated ecological risk. To evaluate the
      transport of trenbolone acetate (TBA) metabolites from beef cattle CAFOs,
      rainfall simulation experiments were conducted at the University of California,
      Davis, research CAFO. Steroid concentrations in solid and aqueous samples from
      the research CAFO and solids samples from a commercial CAFO were analyzed by gas
      chromatography-tandem mass spectrometry. The data indicate that 17alpha
      trenbolone (17alpha-TBOH), 17beta-trenbolone (17beta-TBOH), and trendione (TBO),
      the three primary TBA metabolites, occur in soils and runoff. Soils at the
      research CAFO contained up to 8.2 (+/-1.1) ng/g-dw of 17alpha-TBOH and 1.2 (+/
      0.1) ng/g-dw of 17beta-TBOH, with slightly higher (~20 ng/g-dw) 17alpha-TBOH
      concentrations observed in commercial CAFO soils. In simulated runoff, 17alpha
      TBOH concentrations of 1-350 ng/L and TBO concentrations from 1-170 ng/L were
      observed. The metabolite 17beta-TBOH intermittently occurred in runoff samples at
      5-26 ng/L and may be correlated to anaerobic soils. Metabolite concentrations
      observed in CAFO runoff correspond to 5-15% of potential maximum steroid
      concentrations predicted by mass balances. First order transformation rates of
      0.028/day (25 day half-life) were estimated for 17alpha-TBOH in CAFO soils.
      Results suggest that ecologically relevant concentrations of TBA metabolites can
      be mobilized from CAFO surfaces in storm runoff and may lead to receiving water
      concentrations at or above ecological effects thresholds for a very limited
      number of discharge scenarios.

PMID- 22404690
TI  - Spectroscopic characterization of coumarin-stained beads: quantification of the
      number of fluorophores per particle with solid-state 19F-NMR and measurement of
      absolute fluorescence quantum yields.
AB  - The rational design of nano- and micrometer-sized particles with tailor-made
      optical properties for biological, diagnostic, and photonic applications requires
      tools to characterize the signal-relevant properties of these typically
      scattering bead suspensions. This includes methods for the preferably
      nondestructive quantification of the number of fluorophores per particle and the
      measurement of absolute fluorescence quantum yields and absorption coefficients
      of suspensions of fluorescent beads for material performance optimization and
      comparison. Here, as a first proof-of-concept, we present the first time
      determination of the number of dye molecules per bead using nondestructive
      quantitative ((19)F) NMR spectroscopy and 1000 nm-sized carboxylated polystyrene
      particles loaded with varying concentrations of the laser dye coumarin 153
      containing a CF(3) group. Additionally, the signal-relevant optical properties of
      these dye-loaded particles were determined in aqueous suspension in comparison to
      the free dye in solvents of different polarity with a custom-built integrating
      sphere setup that enables spectrally resolved measurements of emission,
      transmission, and reflectance as well absolute fluorescence quantum yields. These
      measurements present an important step toward absolute brightness values and
      quantitative fluorescence analysis with particle systems that can be exploited,
      for example, for optical imaging techniques and different fluorescence assays as
      well as for the metrological traceability of fluorescence methods.

PMID- 22404691
TI  - Impact of guideline-concordant antibiotics and macrolide/beta-lactam combinations
      in 3203 patients hospitalized with pneumonia: prospective cohort study.
AB  - For patients hospitalized with pneumonia, guidelines provide empirical antibiotic
      recommendations and some studies suggest that macrolide/beta-lactam combinations
      are preferable. We hypothesized that guideline-concordant regimens, particularly
      macrolide/beta-lactams, would reduce mortality and ICU admissions. All patients
      hospitalized with pneumonia in Edmonton, Alberta, Canada, were managed according
      to a clinical pathway and enrolled in a population-based registry. Clinical data,
      Pneumonia Severity Index and treatments were collected. Guideline-concordant
      regimens were macrolides/beta-lactams or respiratory fluoroquinolone monotherapy.
      The main outcome was in-hospital mortality. The study included 3203 patients and
      most had severe pneumonia (63% PSI Class IV-V). Three hundred and twenty-one
      (10.0%) patients died, 306 (9.6%) were admitted to the ICU and 570 (17.8%)
      achieved the composite of death or ICU admission. Most (n = 2506) patients
      received guideline-concordant antibiotics. Receipt of guideline-concordant
      antibiotics was not associated with a reduction in mortality alone (231 (9.2%)
      vs. 90 (12.9%); adjusted odds ratio (aOR), 0.82; 95% CI, 0.61-1.09; p 0.16), but
      was associated with decreased death or ICU admission (14.7% vs. 29.0%; aOR, 0.44;
      95% CI, 0.36-0.54; p < 0.0001). Within guideline-concordant subgroups, there was
      no difference in mortality between macrolide/beta-lactams and respiratory
      fluoroquinolone monotherapy (22 (8.3%) vs. 209 (9.3%); aOR, 1.09; 95% CI, 0.66
      1.81; p 0.73) but macrolide/beta-lactams were associated with increased odds of
      death or ICU admission (17.4% vs. 14.4%; aOR, 1.58; 95% CI, 1.09-2.27; p 0.01).
      In conclusion, guideline-concordant antibiotics were not associated with
      decreased mortality for patients hospitalized with pneumonia, but were associated
      with a decrease in the composite endpoint of death or ICU admission. Our findings
      do not support any clinical advantage of macrolide/beta-lactam compared with
      respiratory fluoroquinolone monotherapy.

PMID- 22404692
TI  - Rapid decline of liver stiffness following alcohol withdrawal in heavy drinkers.
AB  - BACKGROUND: Measurement of liver stiffness (LS) using real-time elastography
      appears as a promising tool to evaluate the severity of chronic liver diseases.
      Previous studies in patients with alcoholic liver disease have suggested that
      fibrosis was the only histological parameter to influence LS. To challenge this
      hypothesis, we have prospectively tested the short-term impact of alcohol
      withdrawal on LS value. METHODS: Patients hospitalized for alcohol withdrawal in
      our Liver and Addiction Unit between 2007 and 2010 had an LS determination at
      entry (D0) and 7 days after alcohol withdrawal (D7). LS value was given as the
      median of 10 measurements performed with a FibroScan((r)) device. For a given
      patient, variation of LS was considered as significant when the comparison of the
      10 measurements at D0 and at D7 yielded a p-value under 0.05 (Wilcoxon test).
      RESULTS: One hundred and thirty-seven patients were included in the study (median
      alcohol consumption: 150 g/d; hepatitis C: n = 21 [15.6%]). Considering all
      patients, median LS value decreased from 7.2 to 6.1 kPa between D0 and D7 (p =
      0.00001, paired Wilcoxon test). LS decreased significantly in 62 patients
      (45.3%), and there was a reduction in the estimated stage of fibrosis in 32
      (23.3%). LS increased significantly in 16 patients (11.7%). Subgroup analyses
      revealed that the decrease in LS was still significant in patients with or
      without hepatitis C infection, and aspartate transaminase level below or above
      100 UI/l. CONCLUSIONS: LS decreases significantly in nearly half of heavy
      drinkers after only 7 days of abstinence. This result strongly suggests that
      nonfibrotic lesions (such as the presence of alcoholic hepatitis) may influence
      LS. From a practical point of view, it also shows that variation of alcohol
      consumption must be taken into account for the interpretation of LS value.

PMID- 22404693
TI  - Evaluation of the North Star Ambulatory Assessment scale and cardiac
      abnormalities in ambulant boys with Duchenne muscular dystrophy.
AB  - AIM: We evaluated ambulatory patients with Duchenne muscular dystrophy from the
      cardiovascular standpoint and studied the correlation between the results of
      electrocardiographic (ECG) findings, left ventricular ejection fraction (LVEF),
      troponin T and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and
      patients' North Star Ambulatory Assessment scores. METHODS: Fifty patients of
      ages 6-12 (8.9 +/- 2.8) were enrolled in this cross-sectional study. Cardiac
      evaluation included electrocardiography, echocardiography and cardiac enzyme
      tests. RESULTS: North Star scores ranged from 6/34 to 34/34. Twenty-eight
      patients (56%) had ECG changes. The most frequently seen ECG abnormalities were
      short PR interval (14%, n= 7), right ventricular hypertrophy (16%, n= 8),
      prolonged QTc interval (10%, n= 5), prominent Q wave (10%, n= 5) and T wave
      inversion (44%, n= 22). In 10 patients (20%), LVEF was below 55%, troponin T and
      NT-proBNP levels were significantly elevated (P= 0.003 and P < 0.001,
      respectively). When North Star scores were compared to patients' age, enzyme
      levels, ECG and echocardiographic results, we discovered negative correlation
      with age (P < 0.001) and troponin T levels (P= 0.02) and positive correlation
      with LVEF (P= 0.02). CONCLUSION: Patients with North Star scores of <=16 are more
      at risk of developing cardiomyopathies. Troponin T is a cardiac index that can be
      used for evaluating myopathic patients and it seems to be correlated with the
      proBNP levels and LVEF values.

PMID- 22404694
TI  - Pegfilgrastim- versus filgrastim-based autologous hematopoietic stem cell
      mobilization in the setting of preemptive use of plerixafor: efficacy and cost
      analysis.
AB  - BACKGROUND: Plerixafor enhances the ability of filgrastim (FIL) to mobilize CD34+
      cells but adds cost to the mobilization. We hypothesized that replacing weight
      based FIL with flat-dose pegfilgrastim (PEG) in a validated cost-based
      mobilization algorithm for patient-adapted use of plerixafor would add
      convenience without increased cost. STUDY DESIGN AND METHODS: A single-center
      retrospective analysis compared two consecutive cohorts undergoing FIL or PEG
      mobilization before autologous hematopoietic stem cell transplantation for
      multiple myeloma or lymphoma. FIL dose was 10 ug/kg/day continuing until
      completion of collection and a 12-mg flat dose of PEG. Peripheral blood CD34+
      cells (PB-CD34+) enumeration was performed on the fourth day after initiation of
      growth factor. Subjects surpassing a certain target-specific threshold of PB
      CD34+ started apheresis immediately while subjects with lower PB-CD34+ received
      plerixafor with apheresis starting on the fifth day. RESULTS: Overall 68 of 74 in
      the FIL group and 52 of 57 patients in the PEG group met the mobilization target.
      Only one patient in each cohort required remobilization. Median PB-CD34+ on Day 4
      was significantly higher in patients in the PEG group (18.1*10(6) vs.
      28.7*10(6)cells/L, p=0.01). Consequently, patients in the PEG group were less
      likely to require administration of plerixafor (67.5% vs. 45.6%, p=0.01). Cohorts
      had near identical mean number of apheresis sessions and comparable CD34+ yield.
      The estimated cost associated with growth factor was higher in patients in the
      PEG group, but it was counterbalanced by lower cost associated with use of
      plerixafor. CONCLUSION: Single administration of 12 mg of PEG is associated with
      better CD34+ mobilization than FIL allowing for effective, convenient
      mobilization with less frequent use of plerixafor.

PMID- 22404695
TI  - Physiological response of Desulfurispirillum indicum S5 to arsenate and nitrate
      as terminal electron acceptors.
AB  - The ability of anaerobic prokaryotes to employ different terminal electron
      acceptors for respiration enables these organisms to flourish in subsurface
      ecosystems. Desulfurispirillum indicum strain S5 is an obligate anaerobic
      bacterium that is able to grow by respiring a range of different electron
      acceptors, including arsenate and nitrate. Here, we examined the growth, electron
      acceptor utilization, and gene expression of D. indicum growing under arsenate
      and nitrate-reducing conditions. Consistent with thermodynamic predictions, the
      experimental results showed that the reduction of nitrate to ammonium yielded
      higher cell densities than the reduction of arsenate to arsenite. However, D.
      indicum grew considerably faster by respiration on arsenate compared with
      nitrate, with doubling times of 4.3 +/- 0.2 h and 19.2 +/- 2.0 h, respectively.
      Desulfurispirillum indicum growing on both electron acceptors exhibited the
      preferential utilization of arsenate before nitrate. The expression of the
      arsenate reductase gene arrA was up-regulated approximately 100-fold during
      arsenate reduction, as determined by qRT-PCR. Conversely, the nitrate reductase
      genes narG and napA were not differentially regulated under the conditions
      tested. The results of this study suggest that physiology, rather than
      thermodynamics, controls the growth rates and hierarchy of electron acceptor
      utilization in D. indicum.

PMID- 22404696
TI  - Complete immunotolerance induction after FEIBA prophylaxis in a haemophilia A
      patient with high-titre inhibitor.

PMID- 22404697
TI  - Effects of Russian current and low-frequency pulsed current on discomfort level
      and current amplitude at 10% maximal knee extensor torque.
AB  - BACKGROUND: Low-frequency pulsed current (LFPC) and Russian current (RC), a type
      of kilohertz-frequency alternating current, have been frequently used for muscle
      strengthening in rehabilitation programs. Despite the popularity of these current
      types, it is unclear which is most effectively able to generate a similar
      submaximal torque with minimal discomfort and current amplitude. OBJECTIVE: To
      compare discomfort and current amplitude between LFPC and RC to achieve a knee
      extensor torque of 10% of the maximal isometric voluntary contraction (MIVC).
      METHODS: Twenty-two healthy subjects were subjected to three electrically
      elicited knee extensor submaximal contractions (10% MIVC) that were sustained for
      10 seconds. The current amplitude required to achieve 10% MIVC and subjective
      discomfort were assessed directly by the electrical stimulator and with the
      Visual Analogue Pain Scale, respectively. A paired t-test was used to determine
      differences between the electrical currents (alpha = 0.05). RESULTS: LFPC
      required significantly lower current amplitude (15%) and a lower discomfort level
      (50%) to achieve 10% of MIVC compared to RC. CONCLUSION: LFPC current seems to be
      more effective than RC with respect to discomfort level and current amplitude to
      produce 10% of MIVC.

PMID- 22404698
TI  - Predictors of depressive symptoms among breast cancer patients during the first
      year post diagnosis.
AB  - It is important to identify predictors of psychological health among breast
      cancer patients that can be relatively easily identified by medical care
      providers. This article investigates the role of one class of such potential
      predictors: easily identified demographics that have potential social and/or
      practical implications. Specifically, we examined whether income, marital status,
      presence of children in the home, education, travel distance, age and rurality
      interact with time to predict psychological health over the first year post
      diagnosis. Two hundred and twenty five breast cancer patients receiving radiation
      treatment completed four surveys over the course of 13 months that included
      measures of both their physical health and depressive symptoms. The results
      revealed that women who were not married had children living in the home or had
      to travel long distances to receive radiation treatment reported higher levels of
      depressive symptoms across the entire study. Women with lower incomes reported
      increased depressive symptoms, but only after the completion of treatment.
      Younger women reported elevated depressive symptoms during initial treatment, but
      this effect dissipated after the completion of treatment. The current results
      suggest that demographic patient characteristics may indeed be useful in
      identifying both when and for whom depressive symptoms are particularly likely to
      be problematic.

PMID- 22404699
TI  - Population history of the Hispaniolan hutia Plagiodontia aedium (Rodentia:
      Capromyidae): testing the model of ancient differentiation on a geotectonically
      complex Caribbean island.
AB  - Hispaniola is a geotectonically complex island consisting of two palaeo-islands
      that docked c. 10 Ma, with a further geological boundary subdividing the southern
      palaeo-island into eastern and western regions. All three regions have been
      isolated by marine barriers during the late Cenozoic and possess
      biogeographically distinct terrestrial biotas. However, there is currently little
      evidence to indicate whether Hispaniolan mammals show distributional patterns
      reflecting this geotectonic history, as the island's endemic land mammal fauna is
      now almost entirely extinct. We obtained samples of Hispaniolan hutia
      (Plagiodontia aedium), one of the two surviving Hispaniolan land mammal species,
      through fieldwork and historical museum collections from seven localities
      distributed across all three of the island's biogeographic regions. Phylogenetic
      analysis using mitochondrial DNA (cytochrome b) reveals a pattern of historical
      allopatric lineage divergence in this species, with the spatial distribution of
      three distinct hutia lineages biogeographically consistent with the island's
      geotectonic history. Coalescent modelling, approximate Bayesian computation and
      approximate Bayes factor analyses support our phylogenetic inferences, indicating
      near-complete genetic isolation of these biogeographically separate populations
      and differing estimates of their effective population sizes. Spatial congruence
      of hutia lineage divergence is not however matched by temporal congruence with
      divergences in other Hispaniolan taxa or major events in Hispaniola's geotectonic
      history; divergence between northern and southern hutia lineages dates to c. 0.6
      Ma, significantly later than the unification of the palaeo-islands. The three
      allopatric Plagiodontia populations should all be treated as distinct management
      units for conservation, with particular attention required for the northern
      population (low haplotype diversity) and the south-western population (high
      haplotype diversity but highly threatened).

PMID- 22404701
TI  - Retraction. Pediatric pulmonary arterial hypertension: current and emerging
      therapeutic options.

PMID- 22404700
TI  - Effects of an oral contraceptive containing chlormadinone acetate and
      ethinylestradiol on hair and skin quality in women wishing to use hormonal
      contraception.
AB  - BACKGROUND: Skin and hair appearance is important to body image. Oily skin and
      oily, impaired hair quality, which can develop in women taking certain types of
      hormonal contraceptives, may cause psychosocial stress. OBJECTIVES: The aim of
      the current study was to investigate the effects of an oral monophasic
      contraceptive (0.03 mg ethinylestradiol/2 mg chlormadinone acetate) for 12
      treatment cycles on the pathophysiology of oily skin and oily, impaired hair
      quality in healthy women. METHODS: We assessed changes in hair and skin
      parameters at baseline, 12, 24 and 48 weeks, in 60 women aged 18-45 years.
      Psychological well-being was verified by two subject self-assessments (Hair
      quality, Hairdex). RESULTS: Data from 31 subjects showed that treatment
      significantly improved sebum excretion at capillitium and forehead, and the
      number of terminal hairs. Visual haptic scores revealed significant decreases in
      capillitium seborrhoea, hair condition/density, capillitium dandruff and
      irritation/redness. Subject self-assessment confirmed improvements in hair
      quality. Treatment was well tolerated. CONCLUSION: Chlormadinone acetate in
      hormonal contraception provides excellent cosmetic and dermatological benefits,
      which can improve psychosocial well-being.

PMID- 22404702
TI  - Porous Pt-Ni-P composite nanotube arrays: highly electroactive and durable
      catalysts for methanol electrooxidation.
AB  - Porous Pt-Ni-P composite nanotube arrays (NTAs) on a conductive substrate in good
      solid contact are successfully synthesized via template-assisted
      electrodeposition and show high electrochemical activity and long-term stability
      for methanol electrooxidation. Hollow nanotubular structures, porous
      nanostructures, and synergistic electronic effects of various elements contribute
      to the high electrocatalytic performance of porous Pt-Ni-P composite NTA
      electrocatalysts.

PMID- 22404703
TI  - Growth hormone treatment 50 years down the line - are we getting value?

PMID- 22404704
TI  - A randomised, placebo-controlled 52-week trial of continued quetiapine treatment
      in recently depressed patients with bipolar I and bipolar II disorder.
AB  - OBJECTIVES: To examine the longer-term efficacy of quetiapine monotherapy in
      bipolar depression in a preplanned pooling of data from the EMBOLDEN I and II
      studies. METHODS: Patients (N = 584) with bipolar I or II disorder (most recent
      episode: depressed) who achieved remission after 8 weeks of treatment with
      quetiapine (300 or 600 mg/day) were randomised to the same quetiapine dose or
      placebo for 26-52 weeks or until mood event recurrence. RESULTS: The risk for
      recurrence of a mood event was significantly lower with quetiapine than placebo
      (HR 0.51 (95% CI: 0.38-0.69); < 0.001). Quetiapine was associated with a lower
      risk for recurrence of depressive events (HR 0.43 (95% CI: 0.30-0.62); P < 0.001)
      but recurrence of manic/hypomanic events was not significantly reduced (HR 0.75
      (95% CI: 0.45-1.24; P = 0.263). There was a lower risk of recurrence of mood
      events in bipolar I (HR 0.58 (95% CI: 0.41-0.82), P = 0.002) and bipolar II
      patients (HR 0.33 (95% CI: 0.18-0.60), P < 0.001). Discontinuation rates due to
      adverse events were 4.3, 4.0 and 1.7% for quetiapine 300 mg/day, 600 mg/day and
      placebo, respectively. Safety data, including changes in lipid and glucose
      parameters, were consistent with the recognized profile of quetiapine.
      CONCLUSIONS: The efficacy of quetiapine monotherapy in bipolar depression is
      maintained during continued treatment for 26-52 weeks. Quetiapine was generally
      well tolerated.

PMID- 22404708
TI  - Rescue therapy for acute migraine, part 3: opioids, NSAIDs, steroids, and post
      discharge medications.
AB  - OBJECTIVE: The final section of this 3-part review analyzes published reports
      involving the acute treatment of migraine with opioids, non-steroidal anti
      inflammatory drugs (NSAIDs), and steroids in the emergency department (ED),
      urgent care, and headache clinic settings, as well as post-discharge medications.
      In the Conclusion, there is a general discussion of all the therapies presented
      in the 3 sections. METHOD: Using the terms ("migraine" AND "emergency") AND
      ("therapy" OR "treatment"), the author searched MEDLINE for reports from ED and
      urgent care settings that involved all routes of medication delivery. Reports
      from headache clinic settings were included only if medications were delivered by
      a parenteral route. RESULTS: Seventy-five reports were identified that compared
      the efficacy and safety of multiple acute migraine medications for rescue. Of the
      medications reviewed in Part 3, opioids, NSAIDs, and steroids all demonstrated
      some effectiveness. When used alone, nalbuphine and metamizole were superior to
      placebo. NSAIDs were inferior to the combination of metoclopramide and
      diphenhydramine. Meperidine was arguably equivalent when compared with ketorolac
      and dihydroergotamine (DHE) but was inferior to chlorpromazine and equivalent to
      the other dopamine antagonists. Steroids afford some protection against headache
      recurrence after the patient leaves the treatment center. CONCLUSIONS: All 3
      opioids most frequently studied - meperidine, tramadol, and nalbuphine - were
      superior to placebo in relieving migraine pain, although meperidine combined with
      promethazine was not. Opioid side effects included dizziness, sedation, and
      nausea. With ketorolac being the most frequently studied drug in the class,
      NSAIDs were generally well tolerated, and they may provide benefit even when
      given late in the migraine attack. The rate of headache recurrence within 24-72
      hours after discharge from the ED can be greater than 50%. Corticosteroids can be
      useful in reducing headache recurrence after discharge. As discussed in Parts 1,
      2, and 3, there are effective medications for provider-administered "rescue" in
      all the classes discussed. Prochlorperazine and metoclopramide are the most
      frequently studied of the anti-migraine medications in the emergent setting, and
      their effectiveness is superior to placebo. Prochlorperazine is superior or
      equivalent to all other classes of medications in migraine pain relief. Although
      there are fewer studies involving sumatriptan and DHE, relatively "migraine
      specific" medications, they appear to be equivalent to the dopamine antagonists
      for migraine pain relief. Lack of comparisons with placebo and the frequent use
      of combinations of medications in treatment arms complicate the comparison of
      single agents to one another. When used alone, prochlorperazine, promethazine,
      metoclopramide, nalbuphine, and metamizole were superior to placebo. Droperidol
      and prochlorperazine were superior or equal in efficacy to all other treatments,
      although they also are more likely to produce side effects that are difficult for
      a patient to tolerate (especially akathisia). Metoclopramide was equivalent to
      prochlorperazine, and, when combined with diphenhydramine, was superior in
      efficacy to triptans and NSAIDs. Meperidine was arguably equivalent when compared
      with ketorolac and DHE but was inferior to chlorpromazine and equivalent to the
      other neuroleptics. Sumatriptan was inferior or equivalent to the neuroleptics
      and equivalent to DHE when only paired comparisons were considered. The overall
      percentage of patients with pain relief after taking sumatriptan was equivalent
      to that observed with droperidol or prochlorperazine.

PMID- 22404709
TI  - Migraine with persistent visual aura.

PMID- 22404710
TI  - Facilitated recruitment of Pdc2p, a yeast transcriptional activator, in response
      to thiamin starvation.
AB  - In Saccharomyces cerevisiae, genes involved in thiamin pyrophosphate (TPP)
      synthesis (THI genes) and the pyruvate decarboxylase structural gene PDC5 are
      transcriptionally induced in response to thiamin starvation. Three positive
      regulatory factors (Thi2p, Thi3p, and Pdc2p) are involved in the expression of
      THI genes, whereas only Pdc2p is required for the expression of PDC5. Thi2p and
      Pdc2p serve as transcriptional activators and each factor can interact with
      Thi3p. The target consensus DNA sequence of Thi2p has been deduced. When TPP is
      not bound to Thi3p, the interactions between the regulatory factors are increased
      and THI gene expression is upregulated. In this study, we demonstrated that Pdc2p
      interacts with the upstream region of THI genes and PDC5. The association of
      Pdc2p or Thi2p with THI gene promoters was enhanced by thiamin starvation,
      suggesting that Pdc2p and Thi2p assist each other in their recruitment to the THI
      promoters via interaction with Thi3p. It is highly likely that, under thiamin
      deprived conditions, a ternary Thi2p/Thi3p/Pdc2p complex is formed and
      transactivates THI genes in yeast cells. On the other hand, the association of
      Pdc2p with PDC5 was unaffected by thiamin. We also identified a DNA element in
      the upstream region of PDC5, which can bind to Pdc2p and is required for the
      expression of PDC5.

PMID- 22404711
TI  - Multiple cis-regulatory elements are involved in the complex regulation of the
      sieve element-specific MtSEO-F1 promoter from Medicago truncatula.
AB  - The sieve element occlusion (SEO) gene family includes several members that are
      expressed specifically in immature sieve elements (SEs) in the developing phloem
      of dicotyledonous plants. To determine how this restricted expression profile is
      achieved, we analysed the SE-specific Medicago truncatula SEO-F1 promoter (PMtSEO
      F1) by constructing deletion, substitution and hybrid constructs and testing them
      in transgenic tobacco plants using green fluorescent protein as a reporter. This
      revealed four promoter regions, each containing cis-regulatory elements that
      activate transcription in SEs. One of these segments also contained sufficient
      information to suppress PMtSEO-F1 transcription in the phloem companion cells
      (CCs). Subsequent in silico analysis revealed several candidate cis-regulatory
      elements that PMtSEO-F1 shares with other SEO promoters. These putative sieve
      element boxes (PSE boxes) are promising candidates for cis-regulatory elements
      controlling the SE-specific expression of PMtSEO-F1. 

PMID- 22404712
TI  - Ethylene in vegetative development: a tale with a riddle.
AB  - The vegetative development of plants is strongly dependent on the action of
      phytohormones. For over a century, the effects of ethylene on plants have been
      studied, illustrating the profound impact of this gaseous hormone on plant
      growth, development and stress responses. Ethylene signaling is under tight self
      control at various levels. Feedback regulation occurs on both biosynthesis and
      signaling. For its role in developmental processes, ethylene has a close and
      reciprocal relation with auxin, another major determinant of plant architecture.
      Here, we discuss, in view of novel findings mainly in the reference plant
      Arabidopsis, how ethylene is distributed and perceived throughout the plant at
      the organ, tissue and cellular levels, and reflect on how plants benefit from the
      complex interaction of ethylene and auxin, determining their shape. Furthermore,
      we elaborate on the implications of recent discoveries on the control of ethylene
      signaling.

PMID- 22404713
TI  - t(12;13)(q14;q31) leading to HMGA2 upregulation in acute myeloid leukaemia.

PMID- 22404714
TI  - Screening of antibiotic susceptibility to beta-lactam-induced elongation of Gram
      negative bacteria based on dielectrophoresis.
AB  - We demonstrate a rapid antibiotic susceptibility test (AST) based on the changes
      in dielectrophoretic (DEP) behaviors related to the beta-lactam-induced
      elongation of Gram-negative bacteria (GNB) on a quadruple electrode array (QEA).
      The minimum inhibitory concentration (MIC) can be determined within 2 h by
      observing the changes in the positive-DEP frequency (pdf) and cell length of GNB
      under the cefazolin (CEZ) treatment. Escherichia coli and Klebsiella pneumoniae
      and the CEZ are used as the sample bacteria and antibiotic respectively. The
      bacteria became filamentous due to the inhibition of cell wall synthesis and cell
      division and cell lysis occurred for the higher antibiotic dose. According to the
      results, the pdfs of wild type bacteria decrease to hundreds of kHz and the cell
      length is more than 10 MUm when the bacterial growth is inhibited by the CEZ
      treatment. In addition, the growth of wild type bacteria and drug resistant
      bacteria differ significantly. There is an obvious decrease in the number of wild
      type bacteria but not in the number of drug resistant bacteria. Thus, the drug
      resistance of GNB to beta-lactam antibiotics can be rapidly assessed.
      Furthermore, the MIC determined using dielectrophoresis-based AST (d-AST) was
      consistent with the results of the broth dilution method. Utilizing this approach
      could reduce the time needed for bacteria growth from days to hours, help
      physicians to administer appropriate antibiotic dosages, and reduce the
      possibility of the occurrence of multidrug resistant (MDR) bacteria.

PMID- 22404715
TI  - Rich coordination of Nd3+ in Mg2Nd13(BO3)8(SiO4)4(OH)3, derived from high
      pressure/high-temperature conditions.
AB  - A neodymium borosilicate, Mg(2)Nd(13)(BO(3))(8)(SiO(4))(4)(OH)(3) (MgNdBSi-1),
      was obtained from a high-temperature (1400  degrees C), solid-state reaction
      under high-pressure conditions (4.5 GPa). MgNdBSi-1 contains six different types
      of Nd(3+) coordination environments with three different ligands: BO(3), SiO(4),
      and OH groups. Mg(2+) cations are only bond to BO(3) groups and form porous two
      dimensional layers based on 12-membered ring fragments. Surprisingly, the OH
      groups are retained at high temperature and reside at the center of Mg-BO(3)
      rings.

PMID- 22404716
TI  - Intravenous iron supplementation after kidney transplantation.
AB  - BACKGROUND: We sought to evaluate the effect of intravenous (IV) iron
      supplementation on hemoglobin (Hb) levels and detect predictors for response.
      METHODS: This is a retrospective cohort study of 81 patients who were treated
      with IV iron post-transplant. We evaluated predictors of response to treatment
      defined as an increase in Hb value of more than 1 g/dL by linear regression
      analysis. RESULTS: Three months after treatment, the mean Hb level increased
      significantly from 9.8 +/- 1.4 g/dL to 11.1 +/- 1.6 g/dL (p < 0.001). A lower
      baseline Hb value (OR: 0.51, 95% CI: 0.33-0.78 per 1 g/dL increase) was the only
      predictor of response at three months. The Hb value in the evaluable 60 patients
      at one yr increased from 9.9 +/- 1.4 g/dL to 11.7 +/- 1.7 g/dL (p < 0.001). Lower
      baseline Hb value (OR: 0.34, 95% CI: 0.18-0.65 per 1 g/dL increase) and a shorter
      time from transplantation (OR: 0.8, 95% CI: 0.68-0.94 per one yr increase) were
      predictors of response. Adverse events were reported in five patients (0.7% of
      doses). The rate of estimated glomerular filtration rate decline was reduced
      following the IV iron treatment -0.34 +/- 1.05 mL/min/month after treatment
      compared with -0.81 +/- 1.11 mL/min/month before treatment (p = 0.013).
      CONCLUSIONS: IV iron treatment was safe and associated with Hb increase in a
      cohort of patients after kidney transplantation.

PMID- 22404717
TI  - Opioid detoxification and naltrexone induction strategies: recommendations for
      clinical practice.
AB  - BACKGROUND: Opioid dependence is a significant public health problem associated
      with high risk for relapse if treatment is not ongoing. While maintenance on
      opioid agonists (i.e., methadone, buprenorphine) often produces favorable
      outcomes, detoxification followed by treatment with the MU-opioid receptor
      antagonist naltrexone may offer a potentially useful alternative to agonist
      maintenance for some patients. METHOD: Treatment approaches for making this
      transition are described here based on a literature review and solicitation of
      opinions from several expert clinicians and scientists regarding patient
      selection, level of care, and detoxification strategies. CONCLUSION: Among the
      current detoxification regimens, the available clinical and scientific data
      suggest that the best approach may be using an initial 2-4 mg dose of
      buprenorphine combined with clonidine, other ancillary medications, and
      progressively increasing doses of oral naltrexone over 3-5 days up to the target
      dose of naltrexone. However, more research is needed to empirically validate the
      best approach for making this transition.

PMID- 22404718
TI  - C4.4A is associated with tumor budding and epithelial-mesenchymal transition of
      colorectal cancer.
AB  - C4.4A is a glycolipid-anchored membrane protein expressed in several human
      malignancies. The aim of this study was to explore the association between C4.4A
      expression at the invasion front of colorectal cancer (CRC) and tumor budding, a
      putative hallmark of cell invasion of CRC. Advanced CRCs (T2-4, n = 126) had a
      budding count of 3.66 +/- 5.66, which was significantly higher than that of T1
      early CRCs (1.75 +/- 2.78, n = 87). C4.4A-positive CRC specimens showed a larger
      budding cell number than C4.4A-negative CRC specimens in T1 CRCs, and especially
      advanced CRCs (9.45 +/- 5.83 vs 1.60 +/- 3.93). Furthermore, we found a
      correlation between the percentage of C4.4A-positive cases and budding count in
      advanced CRC. Multivariate analysis for patients' survival showed that C4.4A was
      superior to tumor budding as a prognostic factor. With siRNA treatment, C4.4A
      levels were associated with cell invasion, but not with proliferation, in HCT116
      and DLD1 cell lines. An immunohistochemical study in a subset of CRCs showed no
      relationship between C4.4A and Ki-67 proliferation marker. In vitro assays using
      HCT116 indicated that C4.4A levels correlated well with epithelial-mesenchymal
      transition (EMT) with regard to cell morphology and alterations of EMT markers
      including E-cadherin, vimentin, and partially N-cadherin. We also found that
      C4.4A expression was significantly associated with loss of E-cadherin and gain of
      beta-catenin in clinical CRC tissue samples. These findings suggest that a tight
      association between C4.4A and tumor budding may, in part, be due to C4.4A
      promoting EMT at the invasive front of CRC.

PMID- 22404719
TI  - Iron chelation therapy in the management of transfusion-related cardiac iron
      overload.
AB  - Iron overload is one of the major causes of morbidity and death in patients
      undergoing chronic transfusion therapy. Furthermore, excessive iron accumulation
      in the heart may result in impaired left ventricular dysfunction. With accurate
      monitoring techniques and treatment regimens, progression of heart complications
      can be followed, and their natural history changed. Iron chelation therapy is the
      mainstay of prevention and reversal of myocardial iron overload. Despite recent
      appraisals of general chelating strategies, the management of iron chelation in
      chronically transfused patients with a focus on the heart has not been
      extensively assessed. New studies published in the past couple of years have
      provided important new data in this topic and therefore this review summarizes
      the major studies that examined the removal of iron from the heart with the iron
      chelators: deferoxamine, deferiprone, and deferasirox. Since chronically
      transfused patients and their cardiac clinical presentations vary widely, this
      review tries to identify--with each drug--the precise scenarios evaluated,
      linking patients' baseline characteristics, clinical setting, and drug intake and
      dosing. Ultimately, by stratifying patients according to their cardiac iron
      overload status and ventricular function, this review identifies possible
      approaches for the initial treatment and follow-up of transfusion-related cardiac
      iron overload.

PMID- 22404720
TI  - Should we treat HCV carriers with normal ALT levels? The '5Ws' dilemma.
AB  - Approximately 30% of patients with chronic HCV infection have persistently normal
      ALT levels. Although formerly referred to as 'healthy' or 'asymptomatic' HCV
      carriers, and thus historically excluded from antiviral treatment, it has now
      become clear that the majority of these patients have some degree of histological
      liver damage that may be significant in up to 20% of cases and might progress
      towards a more severe degree of liver fibrosis. A significant proportion of
      patients experience periods of increased serum ALT associated with enhanced
      disease progression. However, controversies still exist in clinical practice
      regarding the definition of 'persistent' ALT normality, the virological and
      histological features of these subjects, the need for liver biopsy, the role of
      noninvasive tools for the assessment of liver fibrosis, the natural history and
      the usefulness of antiviral treatment. The advent of new therapeutic options
      (pegylated interferon plus ribavirin) has shifted treatment targets towards the
      eradication of underlying infection, with therapy decision based on age, severity
      of disease and likelihood of response rather than on aminotransferase levels.
      This review is aimed at approaching the main unresolved issues on this topic,
      trying to give evidence-based answers to the more frequently asked questions from
      patients and their physicians.

PMID- 22404721
TI  - Standardization of terminology of virological response in the treatment of
      chronic hepatitis C: panel recommendations.
AB  - The treatment paradigm for hepatitis C virus (HCV) infection is at a critical
      point in its evolution. The addition of a protease inhibitor to peginterferon
      plus ribavirin has become the new standard-of-care treatment for most patients.
      Data from clinical trials of new antivirals have been difficult to interpret and
      compare, partly because of heterogeneity in trial design, and partly because of
      inconsistencies in terminology used to define viral responses and the populations
      evaluated. Present definitions of viral responses for treatment with
      peginterferon and ribavirin are insufficient for novel treatment paradigms.
      Further, categorization of prior patient treatment experience in clinical trials,
      particularly of nonresponders to prior therapy, is inconsistent. Existing terms
      and definitions must be updated, standardized and/or redefined for easier
      interpretation of data and effective communication among clinicians. A panel of
      experts in HCV infection treatment met on 3 December 2009. Goals of the panel
      were to evaluate terms and definitions used traditionally in treatment with
      peginterferon and ribavirin, to refine and clarify definitions of existing terms
      that have varying meanings and to propose new terms and definitions appropriate
      for novel treatment paradigms emerging with development of new agents. A number
      of recommendations were accepted unanimously by the panel. Adoption of these
      terms would improve communication among investigators, enhance comparability
      among clinical trials, facilitate development of therapeutic guidelines and
      provide a standardized terminology for use in clinical practice.

PMID- 22404722
TI  - Novel controlled attenuation parameter for noninvasive assessment of steatosis
      using Fibroscan((r)): validation in chronic hepatitis C.
AB  - A novel controlled attenuation parameter (CAP) has been developed for
      Fibroscan((r)) to assess liver steatosis, simultaneously with liver stiffness
      measurement (LSM). We assessed CAP diagnostic accuracy in a large cohort of
      patients with chronic hepatitis C (CHC) virus. A total of 615 patients with CHC,
      who underwent both Fibroscan((r)) and liver biopsy, were analysed. Fibrosis was
      graded using METAVIR score. Steatosis was categorized by visual assessment as
      S(0) : steatosis in <10% of hepatocytes, S(1) : 11-33%, S(2) : 34-66% and S(3) :
      67-100%. Performances of CAP and liver stiffness were determined using receiver
      operating characteristic (ROC) curve analysis and cross-validated using the
      bootstrap method. The Obuchowski measure was used to assess overall accuracy of
      CAP and to differentiate between steatosis grades. In multivariate analysis, CAP
      was related to steatosis (P < 10(-15) ) independently of fibrosis stage (which
      was related to LSM). The areas under ROC curves using CAP to detect steatosis
      were 0.80 (95% CI, 0.75-0.84) for S >= S(1) , 0.86 (0.81-0.92) for S >= S(2) and
      0.88 (0.73-1) S = S(3) . CAP exhibited a good ability to differentiate steatosis
      grades (Obuchowski measure = 0.92). Performance of LSM for fibrosis assessment
      confirmed results from previous studies. CAP is a novel tool to assess the degree
      of steatosis and both fibrosis and steatosis can be evaluated noninvasively
      during the same procedure using Fibroscan((r)) , in patients with CHC.

PMID- 22404723
TI  - Lymphotropic hepatitis C virus has an interferon-resistant phenotype.
AB  - Hepatitis C virus (HCV) infects and associates with B cells, leading to abnormal
      B-cell activation and development of lymphoproliferative and autoimmune
      disorders. This immune perturbation may in turn be associated with the resistance
      of HCV against the host immune system. The objective of this study was to analyse
      the effects of HCV infection of B cells on the efficacy of interferon (IFN)-based
      therapy. The study enrolled 102 patients with chronic hepatitis C who were
      treated with pegylated IFN plus ribavirin. HCV RNA titres in B cells were
      compared in patients with rapid viral responder (RVR) vs non-RVR, sustained viral
      responder (SVR) vs non-SVR and null viral responder (NVR) vs VR. The levels of
      HCV RNA in B cells were significantly higher in non-RVR, non-SVR and NVR groups.
      Association between the therapy outcome and the positive B-cell HCV RNA was also
      investigated in relation to other known viral and host factors. Multivariable
      analyses showed that the positive B-cell HCV RNA and the minor single-nucleotide
      polymorphism near the IL28B gene (rs8099917) were independent factors associated
      with NVR in patients infected with HCV genotype 1. When these two factors were
      combined, the sensitivity, specificity, positive and negative predictive values
      for NVR were 92.3%, 98.2%, 92.3% and 98.2%, respectively. Genotype 1 and the
      presence of one or no mutations in the IFN-sensitivity determining region were
      associated with higher levels of B-cell HCV RNA. B-cell-tropic HCV appears to
      have an IFN-resistant phenotype. B-cell HCV RNA positivity is a predictive factor
      for resistance to IFN-based therapy.

PMID- 22404724
TI  - Durability of sustained response shown in paediatric patients with chronic
      hepatitis C who were treated with interferon alfa-2b plus ribavirin.
AB  - Long-term studies in adults indicate that sustained virologic response (SVR)
      after combination treatment for chronic hepatitis C (CHC) predicts long-term
      clearance. Although peginterferon plus ribavirin is now standard care for
      children with CHC, long-term follow-up studies are not yet available. This study
      evaluated durability of virologic response over 5 years in children previously
      treated with interferon alfa-2b plus ribavirin (IFN/R). Ninety-seven of 147
      children with CHC, who were treated with IFN/R and completed the 6-month follow
      up in two previous clinical trials, participated in this long-term follow-up
      study. All were assessed annually for up to 5 years; patients with SVR were
      assessed for durability of virologic response. Children with SVR (n = 56) and
      those with detectable hepatitis C virus (HCV) RNA 24-week post-treatment (n = 41)
      were followed for a median of 284 weeks. Overall, 70% (68/97) of patients
      completed the 5-year follow-up. One patient with genotype 1a CHC had SVR and
      relapsed at year 1 of follow-up with the same genotype. Kaplan-Meier estimate for
      sustained response at 5 years was 98% (95% CI: 95%, 100%). Six patients with low
      positive HCV RNA levels (n = 4) or missing HCV RNA at the 24-week follow-up visit
      (n = 2) in the initial treatment studies had virologic response during this long
      term follow-up study. Linear growth rate was impaired during treatment with rapid
      increases in the immediate 6 months post-treatment. Mean height percentile at the
      end of the 5-year follow-up was slightly less than the mean pretreatment height
      percentile. Five patients experienced serious adverse events; none related to
      study drug exposure. SVR after IFN/R predicts long-term clearance of HCV in
      paediatric patients; growth normalized in the majority of children during the
      long-term follow-up. Similar long-term results could be expected after
      peginterferon alfa-2b plus ribavirin treatment.

PMID- 22404725
TI  - Risk of myocardial infarction associated with chronic hepatitis C virus
      infection: a population-based cohort study.
AB  - Hepatitis C virus (HCV) infection is associated with systemic inflammation and
      metabolic complications that might predispose patients to atherosclerosis.
      However, it remains unclear if HCV infection increases the risk of acute
      myocardial infarction (MI). To determine whether HCV infection is an independent
      risk factor for acute MI among adults followed in general practices in the United
      Kingdom (UK), a retrospective cohort study was conducted in The Health
      Improvement Network, from 1996 through 2008. Patients >=18 years of age with at
      least 6 months of follow-up and without a prior history of MI were eligible for
      study inclusion. HCV-infected individuals, identified with previously validated
      HCV diagnostic codes (n = 4809), were matched on age, sex and practice with up to
      15 randomly selected patients without HCV (n = 71 668). Rates of incident MI
      among patients with and without a diagnosis of HCV infection were calculated.
      Adjusted hazard ratios were estimated using Cox proportional hazards regression,
      controlling for established cardiovascular risk factors. During a median follow
      up of 3.2 years, there was no difference in the incidence rates of MI between HCV
      infected and -uninfected patients (1.02 vs 0.92 events per 1000 person-years; P =
      0.7). HCV infection was not associated with an increased risk of incident MI
      (adjusted HR, 1.10; 95% confidence interval [CI], 0.67-1.83). Sensitivity
      analyses including the exploration of a composite outcome of acute MI and
      coronary interventions yielded similar results (adjusted HR, 1.16; 95% CI, 0.77
      1.74). In conclusion, HCV infection was not associated with an increased risk of
      incident MI.

PMID- 22404726
TI  - Elevated serum CK18 levels in chronic hepatitis C patients are associated with
      advanced fibrosis but not steatosis.
AB  - Cytokeratin-18 (CK-18) is a major intermediate filament protein in liver cells.
      The M30 fragment of CK-18 has been identified as a useful marker of apoptosis
      associated with fibrosis and steatosis in nonalcoholic steatohepatitis (NASH). We
      sought to assess the relationship of this marker and steatosis in a cohort of
      adult patients with chronic hepatitis C. The study cohort included sera from 267
      treatment-naive chronic hepatitis C (CHC) patients and 100 healthy controls with
      normal alanine aminotransferase (ALT). Biopsies from CHC patients were assessed
      for METAVIR fibrosis stage, Histology Activity Index (HAI) inflammation score and
      steatosis grade by expert histopathologists. The M30 fragment of CK-18 was
      quantified by ELISA. Wilcoxon Rank Sum, Spearman Correlation and Linear
      Regression tests were performed for statistical analysis. Median CK-18 levels
      were higher in CHC patients compared to controls (411 vs 196 U/L, P < 0.0001).
      Fibrosis stage was associated with increasing serum CK-18 levels (P = 0.015) and
      CK-18 levels were higher for F2-F4 vs F0-F1 (500 vs 344 U/L; P = 0.001). There
      was no association between CK-18 and increasing steatosis grade 1, 2 or 3 (460.7
      vs 416.8 vs 508.3 U/L; P = 0.35) and presence or absence of steatosis (445.3 vs
      365.8 U/L; P = 0.075). Fibrosis stage was independently associated with serum M30
      in a multivariable linear regression model (P = 0.03). CK-18 levels were higher
      in CHC compared to healthy controls and associated with hepatic fibrosis. There
      was no difference in CK-18 M30 levels between CHC patients with and without
      steatosis. Although apoptosis may still contribute to hepatitis C virus (HCV)
      mediated steatosis, our results suggest that serum CK-18 will not be a clinically
      useful test for identifying significant steatosis in CHC.

PMID- 22404727
TI  - Reversal of nonstructural protein 3-specific CD4(+)  T cell dysfunction in
      patients with persistent hepatitis C virus infection.
AB  - Hepatitis C virus (HCV)-specific T cell responses are essential for HCV control,
      and chronic infection is characterized by functionally altered antigen-specific T
      cells. It has been proposed that the early inactivation of specific CD4(+) T cell
      responses may be involved in establishment of HCV persistence. We have
      investigated whether HCV-specific CD4(+) T cells dysfunction can be reversed in
      vitro. Nonstructural protein 3 (NS3) and core-specific CD4(+) T cells from eight
      chronically infected and eight spontaneously resolved HCV individuals were
      selected through transient CD154 (CD40 ligand) expression, and their functional
      profile (IFN-gamma, IL-2, TNF-alpha, IL-10 and IL-4 production by enzyme-linked
      immunospot assay, cytometric bead array and intracellular cytokine staining, and
      proliferation by carboxy-fluorescein diacetate succinimidyl ester dilution assay)
      was determined both ex vivo and after in vitro expansion of sorted CD154
      expressing cells in the absence of specific antigen in IL-7/IL-15-supplemented
      medium. Ex vivo bulk CD4(+) T cells from chronic patients expressed CD154 in most
      cases, albeit at lower frequencies than those of resolved patients (0.11%vs
      0.41%; P = 0.01), when stimulated with NS3, but not core, although they had a
      markedly impaired capacity to produce IL-2 and IFN-gamma. Antigen-free in vitro
      expansion of NS3-specific CD154(+) cells from chronic patients restored IFN-gamma
      and IL-2 production and proliferation to levels similar to those of patients with
      spontaneously resolved infection. Hence, NS3-specific CD4(+) T cell response can
      be rescued in most chronic HCV patients by in vitro expansion in the absence of
      HCV-specific antigen. These results might provide a rationale for adoptive
      immunotherapy.

PMID- 22404728
TI  - Inhibition effect produced by dominant negative mutant fusion protein PreS2-TLM
      ScFv-HBcDN on HBV replication in vitro.
AB  - A mammalian expression vector comprised of the PreS2-TLM (translocation motif), a
      single-chain variable fragment (ScFv) that binds to hepatitis B surface antigen
      (HBsAg) and the EGFP gene was constructed. A stably transformed cell line that
      could express and secrete the fusion protein (PreS2-TLM-ScFv-EGFP) was
      established. HBsAg-positive HepG2.2.15 cells and HepG2 and HeLa cells were
      incubated with the supernatant of the transformed cell line cultures for
      evaluating the cellular permeability of PreS2-TLM-ScFv-EGFP. The location of the
      fusion protein PreS2-TLM-ScFv-EGFP in HepG2.2.15 cells was observed with
      immunofluorescence staining. EGFP was next replaced by a dominant negative mutant
      of the hepatitis B virus core gene (HBcDN) for producing fusion protein PreS2-TLM
      ScFv-HBcDN, which was detected by western blot. The supernatant containing fusion
      protein PreS2-TLM-ScFv-HBcDN was added to the cultures of HepG2.2.15 cells, and
      the packaged hepatitis B virus (HBV) pregenomic RNA expression levels in the
      cells were measured using qRT-PCR. The results of the in vitro study indicated
      that the packaged HBV pregenomic RNA expression levels in HepG2.2.15 cells
      significantly decreased when these cells were exposed to the supernatant at the
      dose of 25% for 24, 48 and 72 h, or at the dose of 12.5% for 72 h.

PMID- 22404729
TI  - Maternal near-miss among women with a migrant background in Germany.
AB  - OBJECTIVE: To examine the association between region of origin and severe illness
      bringing a mother close to death (near-miss). DESIGN: Retrospective cohort study.
      SETTING: Maternity units in Lower Saxony, Germany. POPULATION: 441 199 mothers of
      singleton newborns in 2001-2007. METHODS: Using chi-squared tests, bivariate and
      multivariable logistic regression we examined the association between maternal
      region of origin and near-miss outcomes with prospectively collected perinatal
      data up to seven days postpartum. MAIN OUTCOME MEASURES: Hysterectomy,
      hemorrhage, eclampsia and sepsis rates. RESULTS: Eclampsia was not associated
      with region of origin. Compared to women from Germany, women from the Middle East
      (OR 2.24; 95%CI 1.60-3.12) and Africa/Latin America/other countries (OR 2.17;
      95%CI 1.15-4.07) had higher risks of sepsis. Women from Asia (OR 3.37; 95%CI 1.66
      6.83) and from Africa/Latin America/other countries had higher risks of
      hysterectomy (OR 2.65; 95%CI 1.36-5.17). Compared to German women, the risk of
      hemorrhage was higher among women from Asia (OR 1.55; 95%CI 1.19-2.01) and lower
      among women from the Middle East (OR 0.66, 95%CI 0.55-0.78). Adjusting for
      maternal age, parity, occupation, partner status, smoking, obesity, prenatal
      care, chronic conditions and infertility showed no association between country of
      origin and risk of sepsis. CONCLUSION: Region of origin was a strong predictor
      for near-miss among women from the Middle East, Asia and Africa/Latin
      America/other countries. Confounders mostly did not explain the higher risks for
      maternal near-miss in these groups of origin. Clinical studies and audits are
      required to examine the underlying causes for these risks.

PMID- 22404730
TI  - Incidence, aetiology and resistance of late-onset neonatal sepsis: a five-year
      prospective study.
AB  - AIM: Investigate the incidence, etiological pattern and the antimicrobial
      resistance of late-onset neonatal infections over a period of 5 years. METHODS:
      Longitudinal audit of neonatal sepsis from January 2005 to December 2009, in the
      main maternity hospital in Kuwait. Late-onset neonatal infection was defined as
      the culture of a single potentially pathogenic organism from blood or
      cerebrospinal fluid from an infant older than 6 days in association with clinical
      or laboratory findings consistent with infection. RESULTS: The overall incidence
      was 16.9 (95% confidence interval: 15.8-18.0) episodes per 1000 live births. The
      commonest pathogen was coagulase-negative Staphylococcus, 339 (35.7%), while
      Klebsiella was the most common gram-negative infection, 178 (18.8%). Escherichia
      coli, Enterococcus and Enterobacter spp were each responsible for 6% of all
      infections. Candida caused 104 (11.0%) infections. The general pattern of
      infection remained unchanged over the study period. Case fatality was 11.7% (95%
      confidence interval: 9.7-13.9%) and was high for Pseudomonas (18.4%) and Candida
      (22.1%) infections. Approximately 24 and 20% of Klebsiella infections were
      resistant to cefotaxime and gentamicin, respectively, while 28 and 24% of
      Escherichia coli infections were resistant to cefotaxime and gentamicin,
      respectively. CONCLUSION: The incidence of late-onset infection in Kuwait is
      high, resembling that in resource-poor countries. The high incidence coupled with
      low case fatality provides an example for settings where tertiary care is
      introduced without strict measures against nosocomial infections. Prevention
      against nosocomial infections in neonatal units has the potential to further
      reduce neonatal mortality in these settings.

PMID- 22404731
TI  - Efficacy and safety of combination of risperidone and haloperidol with
      divalproate in patients with acute mania.
AB  - OBJECTIVE: The current study evaluated the efficacy and safety of risperidone and
      haloperidol as an adjunctive agent in combination with divalproate in patients
      with an episode of acute mania. METHODS: This 6-week randomized, single-blind
      study was conducted in psychiatric wards of a mental hospital. A total of 41
      patients were randomly assigned to the risperidone (risperidone plus divalproate)
      or haloperidol groups (haloperidol plus divalproate). Efficacy was assessed by
      changes in symptom rating scales [Young Mania Rating Scale (YMRS), Brief
      Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI) scores].
      Safety and tolerability were assessed by monitoring the Extrapyramidal Symptom
      Rating Scale (ESRS) and Hamilton Rating Scale for depression. RESULTS: Mean doses
      at baseline, and at weeks 4 and 6 were 3.77, 4.95 and 5.00 mg/day of risperidone
      and 5.89, 9.95 and 8.58 mg/day of haloperidol, respectively. Risperidone was
      shown to have significant anti-manic effects which was observed as early as week
      1, following start of treatment. The BPRS scores were in favor of risperidone at
      week 2. Patients receiving risperidone exhibited significant greater global
      improvement on the CGI, as early as week 2 and over the entire treatment period,
      than haloperidol after 4 weeks of treatment. The ESRS at endpoint were
      significantly higher in the haloperidol patients. CONCLUSIONS: Risperidone plus
      divalproate was more efficacious than haloperidol plus divalproate for treatment
      of acute mania, and was well tolerated due to its evidence showing rapid anti
      manic action, effective and sustained control of manic and psychotic symptoms and
      a favorable safety and tolerability profile in acute mania.

PMID- 22404732
TI  - Anidulafungin for the treatment of candidaemia/invasive candidiasis in selected
      critically ill patients.
AB  - A prospective, multicentre, phase IIIb study with an exploratory, open-label
      design was conducted to evaluate efficacy and safety of anidulafungin for the
      treatment of candidaemia/invasive candidiasis (C/IC) in specific ICU patient
      populations. Adult ICU patients with confirmed C/IC meeting >= 1 of the following
      criteria were enrolled: post-abdominal surgery, solid tumour, renal/hepatic
      insufficiency, solid organ transplant, neutropaenia, and age >= 65 years.
      Patients received anidulafungin (200 mg on day 1, 100 mg/day thereafter) for 10
      42 days, optionally followed by oral voriconazole/fluconazole. The primary
      efficacy endpoint was global (clinical and microbiological) response at the end
      of all therapy (EOT). Secondary endpoints included global response at the end of
      intravenous therapy (EOIVT) and at 2 and 6 weeks post-EOT, survival at day 90,
      and incidence of adverse events (AEs). The primary efficacy analysis was
      performed in the modified intent-to-treat (MITT) population, excluding
      unknown/missing responses. The safety and MITT populations consisted of 216 and
      170 patients, respectively. The most common pathogens were Candida albicans
      (55.9%), C. glabrata (14.7%) and C. parapsilosis (10.0%). Global success was
      69.5% (107/154; 95% CI, 61.6-76.6) at EOT, 70.7% (111/157) at EOIVT, 60.2%
      (77/128) at 2 weeks post-EOT, and 50.5% (55/109) at 6 weeks post-EOT. When
      unknown/missing responses were included as failures, the respective success rates
      were 62.9%, 65.3%, 45.3% and 32.4%. Survival at day 90 was 53.8%. Treatment
      related AEs occurred in 33/216 (15.3%) patients, four (1.9%) of whom had serious
      AEs. Anidulafungin was effective, safe and well tolerated for the treatment of
      C/IC in selected groups of ICU patients.

PMID- 22404733
TI  - The International Alcohol Control (IAC) study-evaluating the impact of alcohol
      policies.
AB  - BACKGROUND: This paper describes a new multicountry collaborative project to
      assess the impact of alcohol control policy. Longitudinal surveys of drinkers in
      a number of participating countries and analysis of the policy context allow for
      the assessment of change over time within countries and comparison between
      countries. The design of the study is modeled on the International Tobacco
      Control study and aims to assess the impact of alcohol policies in different
      cultural contexts on policy-related behaviors and alcohol consumption. A survey
      instrument and protocol for policy analysis have been developed by the initial
      participating countries: England, Scotland, Thailand, South Korea, and New
      Zealand. The first round of data collection is scheduled for 2011-2012.
      MEASUREMENTS: The survey instrument (International Alcohol Control [IAC] survey)
      measures key policy relevant behaviors: place and time of purchase, amounts
      purchased and price paid; ease of access to alcohol purchase; alcohol marketing
      measures; social supply; perceptions of alcohol affordability and availability
      and salience of price; perceptions of enforcement; people's experiences with
      specific alcohol restrictions; support for policy and consumption (typical
      quantity, frequency using beverage and location-specific measures). The Policy
      Analysis Protocol (PoLAP) assesses relevant aspects of the policy environment
      including regulation and implementation. RESULTS: It has proved feasible to
      design instruments to collect detailed data on behaviors relevant to alcohol
      policy change and to assess the policy environment in different cultural
      settings. CONCLUSIONS: In a policy arena in which the interest groups and
      stakeholders have different perceptions of appropriate policy responses to
      alcohol-related harm, a robust methodology to assess the impact of policy will
      contribute to the debate.

PMID- 22404734
TI  - Large demyelinating lesions: a neurosurgical perspective.
AB  - OBJECT/ BACKGROUND: Large demyelinating lesions (LDLs) may present with unusual
      features like seizures and significant mass effect and often masquerade a tumour.
      Even radiological features are confusing. With clinical signs of increased intra
      cranial pressure (ICP), decompressive surgery becomes life-saving. However,
      resection of the involved nervous tissue is unnecessary and may lead to permanent
      residual deficits that otherwise can be avoided. MATERIAL AND METHODOLOGY: We
      present a series of eight patients with focal deficits and/or raised pressure
      symptoms wherein a diagnosis of tumour was made preoperatively. The clinico
      radiological picture and outcome has been described. RESULTS: Clinically, all
      these patients had focal deficits and five had raised ICP. Three patients had
      seizures. Two patients had long standing visual deterioration in one eye.
      Radiology showed irregular enhancement in two and concentric rings in one. The
      deep grey matter was involved in one and cortex in four. Biopsy/decompressive
      surgery and resection of lesion improved the sensorium in all, but focal deficits
      persisted. Two patients died after being discharged in a conscious state, and one
      died in hospital. CONCLUSION: High index of suspicion is required to diagnose
      demyelination prior to surgery. Unexplained long standing clinical features,
      radiology that has contrast enhancement patterns and mass effect (dissociation
      between contrast enhancement and mass effect) that is unusual for glioma should
      raise the suspicion of such non-neoplastic lesions. For patients with minimal
      mass effect with focal deficits, open/stereotactic biopsy from multiple areas of
      the lesion is preferable for diagnosis. Those presenting with mass effect,
      decompressive craniectomy and biopsy from the lesion is preferable than
      attempting complete resection especially in and around the eloquent areas. A
      second look surgery to resect the lesion can always be undertaken once
      histopathology suggests a neoplastic etiology and rules out a demyelinating
      lesion.

PMID- 22404735
TI  - Clinical outcomes from bilateral versus unilateral stimulation of the
      pedunculopontine nucleus with and without concomitant caudal zona incerta region
      stimulation in Parkinson's disease.
AB  - INTRODUCTION: The Pedunculopontine nucleus is a novel target for deep brain
      stimulation and this may improve postural instability and gait dysfunction in
      Parkinson's disease. If unilateral Pedunculopontine nucleus stimulation is as
      efficacious as bilateral stimulation this would lead to less surgical risk.
      METHODS: 5 Parkinson's disease patients with bilateral caudal Zona Incerta region
      and Pedunculopontine nucleus electrodes were assessed using the motor component
      of the Unified Parkinson's Disease Rating Scale. Patients were assessed in the on
      medication state to determine the optimal combination of stimulation setting for
      axial symptom control. RESULTS: The on-medication composite axial-subscore only
      showed a statistically significant improvement when bilateral Pedunculopontine
      nucleus and caudal Zona Incerta region stimulation was used. CONCLUSIONS: In the
      on-medication state bilateral Pedunculopontine nucleus and caudal Zona Incerta
      region stimulation is required in order to produce a significant change in the
      motor Unified Parkinson's Disease Rating Scale axial-subscore from baseline.

PMID- 22404736
TI  - Isolation and characterisation of Chrysanthemum crassum SOS1, encoding a putative
      plasma membrane Na(+) /H(+) antiporter.
AB  - A full-length cDNA homologue of SOS1 (salt overly sensitive 1) was isolated from
      the salinity-tolerant species Chrysanthemum crassum and found to encode a Na(+)
      /H(+) antiporter, using degenerate PCR and RACE-PCR. The 3752-bp sequence
      comprised a 3438 bp open reading frame, encoding a 127-kDa protein with 12
      transmembrane domains within its N terminal portion, and a hydrophilic
      cytoplasmic tail in its C-terminal portion. CcSOS1 appears to be a plasma
      membrane protein, and shares ~62% identity at the peptide level with its
      Arabidopsis thaliana homologue. Expression of CcSOS1 in the roots of C. crassum
      was sensitive to salinity stress, while in the leaves CcSOS1 was down-regulated
      in the presence of abscisic acid. CcSOS1 transcript abundance was reduced in both
      roots and leaves of plants exposed to low temperature, while it was increased in
      leaves (but not in roots) after drought stress. CcSOS1 expression was not
      regulated in the presence of CaCl2 . A heterologous complementation assay in
      yeast suggested that CcSOS1 directs Na(+) efflux, mimicking the function of the
      endogenous NHA1 protein. Thus CcSOS1 appears to encode a salinity-inducible
      plasma membrane Na(+) /H(+) antiporter. This gene may be useful in transgenic
      approaches to improving the salinity tolerance of related ornamental species. 

PMID- 22404737
TI  - Coarse-graining intermolecular interactions in dispersions of highly charged
      colloids.
AB  - Effective pair potentials between charged colloids, obtained from Monte Carlo
      simulations of two single colloids in a closed cell at the primitive model level,
      are shown to reproduce accurately the structure of aqueous salt-free colloidal
      dispersions, as determined from full primitive model simulations by Linse et al.
      (Linse, P.; Lobaskin, V. Electrostatic Attraction and Phase Separation in
      Solutions of Like-Charged Colloidal Particles. Phys. Rev. Lett.1999, 83, 4208).
      Excellent agreement is obtained even when ion-ion correlations are important and
      is in principle not limited to spherical particles, providing a potential route
      to coarse-grained colloidal interactions in more complex systems.

PMID- 22404738
TI  - A realistic utilization of nanotechnology in molecular imaging and targeted
      radiotherapy of solid tumors.
AB  - Precise dose delivery to malignant tissue in radiotherapy is of paramount
      importance for treatment efficacy while minimizing morbidity of surrounding
      normal tissues. Current conventional imaging techniques, such as magnetic
      resonance imaging (MRI) and computerized tomography (CT), are used to define the
      three-dimensional shape and volume of the tumor for radiation therapy. In many
      cases, these radiographic imaging (RI) techniques are ambiguous or provide
      limited information with regard to tumor margins and histopathology. Molecular
      imaging (MI) modalities, such as positron emission tomography (PET) and single
      photon-emission computed-tomography (SPECT) that can characterize tumor tissue,
      are rapidly becoming routine in radiation therapy. However, their inherent low
      spatial resolution impedes tumor delineation for the purposes of radiation
      treatment planning. This review will focus on applications of nanotechnology to
      synergize imaging modalities in order to accurately highlight, as well as
      subsequently target, tumor cells. Furthermore, using such nano-agents for
      imaging, simultaneous coupling of novel therapeutics including radiosensitizers
      can be delivered specifically to the tumor to maximize tumor cell killing while
      sparing normal tissue.

PMID- 22404739
TI  - Mitigation of radiation-induced dermatitis by activation of aldehyde
      dehydrogenase 2 using topical alda-1 in mice.
AB  - Radiation-induced dermatitis is a debilitating clinical problem in cancer
      patients undergoing cancer radiation therapy. It is also a possible outcome of
      exposure to high levels of radiation due to accident or hostile activity. We
      report that activation of aldehyde dehydrogenase 2 (ALDH2) enzymatic activity
      using the allosteric agonist, Alda-1, significantly reduced 4-hydroxynonenal
      adducts accumulation, delayed the onset of radiation dermatitis and substantially
      reduced symptoms in a clinically-relevant model of radiation-induced dermatitis.
      Importantly, Alda-1 did not radioprotect tumors in mice. Rather, it increased the
      sensitivity of the tumors to radiation therapy. This is the first report of
      reactive aldehydes playing a role in the intrinsic radiosensitivity of normal and
      tumor tissues. Our findings suggest that ALDH2 represents a novel target for the
      treatment of radiation dermatitis without reducing the benefit of radiotherapy.

PMID- 22404740
TI  - Nonadditive indirect effects of group genetic diversity on larval viability in
      Drosophila melanogaster imply key role of maternal decision-making.
AB  - Genetic variation can have important consequences for populations: high
      population genetic diversity is typically associated with ecological success.
      Some mechanisms that account for these benefits assume that local social groups
      with high genetic diversity are more successful than low-diversity groups. At the
      same time, active decision-making by individuals can influence group genetic
      diversity. Here, we examine how maternal decisions that determine group genetic
      diversity influence the viability of Drosophila melanogaster larvae. Our groups
      contained wild-type larvae, whose genetic diversity we manipulated, and
      genetically marked 'tester' larvae, whose genotype and frequency were identical
      in all trials. We measured wild-type and tester viability for each group.
      Surprisingly, the viability of wild-type larvae was neither augmented nor reduced
      when group genetic diversity was altered. However, the viability of the tester
      genotype was substantially depressed in large, high-diversity groups. Further,
      not all high-diversity groups produced this effect: certain combinations of wild
      type genotypes were deleterious to tester viability, while other groups of the
      same diversity-but containing different wild-type genotypes-were not deleterious.
      These deleterious combinations of wild-type genotypes could not be predicted by
      observing the performance of the same tester and wild-type genotypes in low
      diversity groups. Taken together, these results suggest that nonadditive
      interactions among genotypes, rather than genetic diversity per se, account for
      between-group differences in viability in D. melanogaster and that predicting the
      consequences of genetic diversity at the population level may not be
      straightforward.

PMID- 22404741
TI  - An evaluation of equivalence in body dissatisfaction measurement across cultures.
AB  - We evaluated gender-based and cross-cultural equivalence of the Body
      Dissatisfaction Scale of the Body Change Inventory in a sample of 4,005
      adolescents from 7 cultures that represent diverse body image ideals and response
      styles. Results of multigroup confirmatory factor analyses demonstrated
      equivalence of the scale across gender but not across cultures. Follow-up
      analyses identified small but significant cross-cultural differences in response
      styles (specifically, acquiescence and middle response option endorsement) as the
      source of this noninvariance. We recommend use of this scale for gender-based
      comparisons but caution that researchers should evaluate the presence of response
      biases before making substantive conclusions about cross-cultural differences in
      body dissatisfaction.

PMID- 22404742
TI  - Kinetics and mechanism of the chlorine dioxide-trithionate reaction.
AB  - The trithionate-chlorine dioxide reaction has been studied spectrophotometrically
      in a slightly acidic medium at 25.0 +/- 0.1  degrees C in acetate/acetic acid
      buffer monitoring the decay of chlorine dioxide at constant ionic strength (I =
      0.5 M) adjusted by sodium perchlorate. We found that under our experimental
      conditions two limiting stoichiometries exist and the pH, the concentration of
      the reactants, and even the concentration of chloride ion affects the actual
      stoichiometry of the reaction that can be augmented by an appropriate linear
      combination of these limiting processes. It is also shown that although the
      formal kinetic order of trithionate is strictly one that of chlorine dioxide
      varies between 1 and 2, depending on the actual chlorine dioxide excess and the
      pH. Moreover, the otherwise sluggish chloride ion, which is also a product of the
      reaction, slightly accelerates the initial rate of chlorine dioxide consumption
      and may therefore act as an autocatalyst. In addition to that, overshoot
      undershoot behavior is also observed in the [(.)ClO(2)]-time curves in the
      presence of chloride ion at chlorine dioxide excess. On the basis of the
      experiments, a 13-step kinetic model with 6 fitted kinetic parameter is proposed
      by nonlinear parameter estimation.

PMID- 22404743
TI  - Sigmoid diverticulitis in 2011: many questions; few answers.
AB  - AIM: Patients were studied after a first episode of acute left-colonic
      diverticulitis for the initial and later evolution of the disease with the aim of
      defining evidence-based indications for elective surgery. METHOD: Relevant data
      from prospective studies were retrieved from a MEDLINE search of English language
      articles. RESULTS: Young male patients (<= 50 years of age) had a higher risk of
      CT-graded severe diverticulitis. After medical treatment of the first episode,
      the incidence of complications was highest for young patients with CT-graded
      severe diverticulitis and lowest for older patients with CT-graded moderate
      diverticulitis. Recurrence in the form of diffuse peritonitis was rare. CT
      grading of initial diverticulitis seemed to be a predictor of recurrence, whereas
      the role of age was less clear. A family history of diverticulitis might be
      predictive of recurrence. CONCLUSION: CT grading of acute diverticulitis helps to
      predict poor outcome after medical treatment of a first episode. Elective
      surgical resection should be proposed to patients with residual symptoms who do
      not respond to conservative treatment. Additional research is needed to clarify
      the role of a genetic predisposition in the development of diverticulitis in
      young adults.

PMID- 22404744
TI  - Maintenance therapy for advanced non-small-cell lung cancer: switch versus
      continuation.
AB  - INTRODUCTION: The concept of maintenance therapy in lung cancer has stirred a
      great deal of interest over the last decade. Several randomized studies have been
      conducted to find out the usefulness of maintenance therapies for advanced non
      small-cell lung cancer (NSCLC). AREAS COVERED: This article reviews the major
      benchmark clinical trials and strategies in the field of maintenance chemotherapy
      in advanced NSCLC. The two strategies used in maintenance therapy are: i)
      continuation maintenance - continuation of one of the initial treatments; and ii)
      switch maintenance - switching to a different agent not administered as initial
      treatment. Both chemotherapeutic and molecular targeted agents have been studied
      in the maintenance setting. These include docetaxel, gemcitabine, pemetrexed,
      bevacizumab, erlotinib and gefitinib. This paper discusses the relevant clinical
      trials using these agents and the two different strategies in the maintenance
      therapy in advanced NSCLC. EXPERT OPINION: Despite some controversy regarding the
      choice or the timing of the maintenance therapy, most of the clinical trials have
      demonstrated a significant improvement of progression-free survival, translating
      to a survival benefit with pemetrexed and erlotinib. The approval of pemetrexed
      and erlotinib by the FDA has certainly shifted the pendulum towards maintenance
      therapy.

PMID- 22404745
TI  - Endothelin-1 enhances the proliferation of normal human melanocytes in a
      paradoxical manner from the TNF-alpha-inhibited condition, but tacrolimus
      promotes exclusively the cellular migration without proliferation: a proposed
      action mechanism for combination therapy of phototherapy and topical tacrolimus
      in vitiligo treatment.
AB  - BACKGROUND: Vitiligo is an acquired pigmentary disorder caused by the destruction
      of melanocytes. Two of the major theories regarding the pathogenesis of vitiligo
      are the autoimmune theory and autocytotoxicity theory, but, the precise
      pathogenetic mechanism is still not clarified. OBJECTIVES: We investigated the
      effects of ET-1, tacrolimus and tumour necrosis factor-alpha (TNF-alpha) on
      proliferation and migration of cultured normal human melanocytes (NHMs). We also
      sought to clarify the theoretical rationale underlying the topical tacrolimus
      monotherapy or tacrolimus-UV combination therapy as tools for vitiligo treatment.
      METHODS: The effects of ET-1, tacrolimus and TNF-alpha on proliferation/migration
      of cultured NHMs were investigated by MTT assay/Boyden chamber transwell
      migration assay. We also examined roles of CXC-chemokine receptor II (CXCR II)
      and matrix metalloproteinases (MMPs) in such conditions. RESULTS: ET-1 exerted a
      stimulatory effect on melanocyte proliferation and migration, but, tacrolimus
      exerted a stimulatory effect only on melanocyte migration higher than ET-1. TNF
      alpha inhibited melanocyte proliferation in a dose-dependent manner.
      Paradoxically, TNF-alpha-pretreated NHMs exhibited an enhanced proliferative
      efficiency after being switched to ET-1. We found CXCRII was highly expressed in
      TNF-alpha-incubated melanocytes than the agents-free control, and ET-1 treatment
      after TNF-alpha preincubation showed the higher levels of CXCRII expression than
      the condition incubated with TNF-alpha alone. Moreover, the greater activities of
      MMP-2 and MMP-9 induced by tacrolimus than ET-1, reflected tacrolimus would
      enhance migration stimulatory effect in cultured NHMs. CONCLUSIONS: Topical
      tacrolimus can be used an effective agent for vitiligo treatment as monotherapy,
      maybe due to its migration stimulatory action or TNF-alpha inhibitory property,
      and also as a component in combination therapy with UV treatment, considering the
      more upregulated MMPs activities are induced and the more effective migrations
      are feasible by itself than ET-1.

PMID- 22404746
TI  - Comparative cytogenetics between the species Passiflora edulis and Passiflora
      cacaoensis.
AB  - Passiflora edulis Sims is the most economically important species of the genus
      Passiflora. A new species was described recently, Passiflora cacaoensis Bernacci
      & Souza, which displayed morphologic characteristics very similar to P. edulis.
      Due to the need for delimitation of the two species, karyomorphological and
      banding analyses were carried out. Both species have 2n = 18, with the same
      karyotype formula 16 m + 2sm. There was variation between the species regarding
      the location of satellites and the width of chromosome pairs 2, 4 and 8. C
      banding revealed the presence of constitutive heterochromatin in the centromeric
      and telomeric regions of all chromosomes in both species. However, only in P.
      cacaoensis did chromosomes 3 and 9 have a large quantity of heterochromatin.
      Fluorochrome banding revealed CMA(+) bands only in the satellites, but no DAPI(+)
      bands. Fluorescence in situ hybridisation (FISH) showed that in P. cacaoensis the
      rDNA 5S probe is located in a single site in the subterminal position of the long
      arm of chromosome 5. However, for the rDNA 45S probe, two sites were detected in
      terminal positions of the long arms of chromosome 7, with a bigger and stronger
      signal, and of chromosome 9. According to the asymmetry index and the quantity of
      heterochromatin, P. cacaoensis is a more basal species than P. edulis. The
      cytogenetic data indicate that P. cacaoensis is closely related to P. edulis, but
      is a different species. 

PMID- 22404747
TI  - Chronic daily headache in U.S. soldiers after concussion.
AB  - OBJECTIVE: To determine the prevalence and characteristics of, and factors
      associated with, chronic daily headache (CDH) in U.S. soldiers after a deployment
      related concussion. METHODS: A cross-sectional, questionnaire-based study was
      conducted with a cohort of 978 U.S. soldiers who screened positive for a
      deployment-related concussion upon returning from Iraq or Afghanistan. All
      soldiers underwent a clinical evaluation at the Madigan Traumatic Brain Injury
      Program that included a history, physical examination, 13-item self-administered
      headache questionnaire, and a battery of cognitive and psychological assessments.
      Soldiers with CDH, defined as headaches occurring on 15 or more days per month
      for the previous 3 months, were compared to soldiers with episodic headaches
      occurring less than 15 days per month. RESULTS: One hundred ninety-six of 978
      soldiers (20%) with a history of deployment-related concussion met criteria for
      CDH and 761 (78%) had episodic headache. Soldiers with CDH had a median of 27
      headache days per month, and 46/196 (23%) reported headaches occurring every day.
      One hundred seven out of 196 (55%) soldiers with CDH had onset of headaches
      within 1 week of head trauma and thereby met the time criterion for posttraumatic
      headache (PTHA) compared to 253/761 (33%) soldiers with episodic headache. Ninety
      seven out of 196 (49%) soldiers with CDH used abortive medications to treat
      headache on 15 or more days per month for the previous 3 months. One hundred
      thirty out of 196 (66%) soldiers with CDH had headaches meeting criteria for
      migraine compared to 49% of soldiers with episodic headache. The number of
      concussions, blast exposures, and concussions with loss of consciousness was not
      significantly different between soldiers with and without CDH. Cognitive
      performance was also similar for soldiers with and without CDH. Soldiers with CDH
      had significantly higher average scores on the posttraumatic stress disorder
      (PTSD) checklist compared to soldiers with episodic headaches. Forty-one percent
      of soldiers with CDH screened positive for PTSD compared to only 18% of soldiers
      with episodic headache. CONCLUSIONS: The prevalence of CDH in returning U.S.
      soldiers after a deployment-related concussion is 20%, or 4- to 5-fold higher
      than that seen in the general U.S. population. CDH following a concussion usually
      resembles chronic migraine and is associated with onset of headaches within the
      first week after concussion. The mechanism and number of concussions are not
      specifically associated with CDH as compared to episodic headache. In contrast,
      PTSD symptoms are strongly associated with CDH, suggesting that traumatic stress
      may be an important mediator of headache chronification. These findings justify
      future studies examining strategies to prevent and treat CDH in military service
      members following a concussive injury.

PMID- 22404748
TI  - Pituitary carcinomas and aggressive pituitary tumours: merits and pitfalls of
      temozolomide treatment.
AB  - Pituitary carcinomas are rare, accounting for about 0.2% of all pituitary
      tumours. They represent a challenge to clinical practice in both diagnosis and
      treatment. They may present initially as typical pituitary adenomas, with a
      delayed appearance of aggressive signs, or as aggressive tumours from the outset.
      Predicting the pituitary tumour behaviour remains difficult: increased mitotic,
      Ki-67 and P53 indices might be associated with tumour aggression. The treatment
      of pituitary carcinomas and aggressive pituitary tumours includes surgery,
      adjuvant medical treatment, external beam radiotherapy and chemotherapy. Until
      recently, the treatment of pituitary carcinomas was mainly palliative and did not
      seem to increase overall survival. Recent case reports have detailed the
      successful use of temozolomide, an orally administered alkylating agent used to
      treat malignant gliomas, in the management of pituitary carcinomas and aggressive
      pituitary tumours. The outcome of treatment might depend on the expression of
      O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme that
      potentially interferes with drug efficacy. This review describes the clinical
      presentation and response to temozolomide in 44 patients with pituitary
      carcinomas or aggressive pituitary tumours reported in the literature. The
      results suggest that temozolomide should be considered a drug of major importance
      in the therapeutic algorithm of aggressive pituitary tumours and pituitary
      carcinomas. Because of the inconsistency of published data, MGMT expression
      should probably not be taken as a reason to deny these patients the potential
      benefit of temozolomide treatment, taking into account the paucity of other
      available treatments.

PMID- 22404749
TI  - Neutrophil gelatinase-associated lipocalin as an early biomarker of acute kidney
      injury in liver transplantation.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common complication and a significant
      prognostic factor of long-term outcome in patients undergoing liver
      transplantation. We evaluated the utility of urine and plasma neutrophil
      gelatinase-associated lipocalin (NGAL) concentrations as biomarkers of AKI during
      and after liver transplantation. MATERIALS AND METHODS: We prospectively enrolled
      19 adult patients who underwent living-related liver transplantation (LRLT).
      Serial blood and urine samples were collected at baseline and at 2, 4, 10, 16,
      24, 30, 40, and 48 h after reperfusion, and their concentrations of NGAL were
      measured, with urinary NGAL corrected by urinary creatinine concentration to
      compensate for urine output. AKI was defined by Risk-Injury-Failure-Loss-End
      stage kidney disease (RIFLE) criteria as a >=50% increase in serum creatinine
      from baseline. RESULTS: Eleven of 19 patients were diagnosed with AKI according
      to RIFLE criteria. Urinary NGAL/urine creatinine ratio increased immediately
      after reperfusion and peaked four h later and preceded a >=50% elevation in serum
      Cr by 19.0 h (p = 0.001). Plasma NGAL also tended to be elevated 13.0 h earlier
      than serum creatinine (p = 0.075). CONCLUSIONS: The urinary NGAL/urine creatinine
      ratio may be an early biomarker of AKI in adult patients undergoing LRLT.

PMID- 22404750
TI  - UGT87A2, an Arabidopsis glycosyltransferase, regulates flowering time via
      FLOWERING LOCUS C.
AB  - * Family 1 glycosyltransferases comprise the greatest number of
      glycosyltransferases found in plants. The widespread occurrence and diversity of
      glycosides throughout the plant kingdom underscore the importance of these
      glycosyltransferases. * Here, we describe the identification and characterization
      of a late-flowering Arabidopsis (Arabidopsis thaliana) mutant, in which a
      putative family 1 glycosyltransferase gene, UGT87A2, was disrupted. The role and
      possible mechanism of UGT87A2 in the regulation of flowering were analyzed by
      molecular, genetic and cellular approaches. * The ugt87a2 mutant exhibited late
      flowering in both long and short days, and its flowering was promoted by
      vernalization and gibberellin. Furthermore, the mutant flowering phenotype was
      rescued by the wild-type UGT87A2 gene in complementation lines. Interestingly,
      the expression of the flowering repressor FLOWERING LOCUS C was increased
      substantially in the mutant, but decreased to the wild-type level in
      complementation lines, with corresponding changes in the expression levels of the
      floral integrators and floral meristem identity genes. The expression of UGT87A2
      was developmentally regulated and its protein products were distributed in both
      cytoplasm and nucleus. * Our findings imply that UGT87A2 regulates flowering time
      via the flowering repressor FLOWERING LOCUS C. These data highlight an important
      role for the family 1 glycosyltransferases in the regulation of plant flower
      development.

PMID- 22404751
TI  - Essential role of macrophages in the initiation of allergic rhinitis in mice
      sensitized intranasally once with cedar pollen: regulation of class switching of
      immunoglobulin in B cells by controlling interleukin-4 production in T cells of
      submandibular lymph nodes.
AB  - The production of allergen-specific IgE antibodies (Abs) in allergen-sensitized
      patients or animals has a mutual relationship with the immunologic response
      leading to allergic rhinitis. We recently reported that, after an intranasal
      injection of cedar pollen into mice, an interleukin-4 (IL-4)-dependent increase
      in serum nonspecific IgE Abs was a prerequisite for the production of serum
      allergen-specific IgE Abs. Here, we explored which lymphoid organs were
      responsive to the intranasally injected allergen and how IL-4 and IgE Abs were
      produced in the lymphocytes. Time-dependent changes in the total cell numbers and
      in in vitro IgE Ab production in various lymphoid organs revealed that the
      submandibular lymph nodes were the main responsible organ. After treatment with
      allergen (for IgE production) or allergen and complete Freund's adjuvant (for IgG
      production), we separated submandibular lymph node cells into macrophage-,
      lymphocyte-, and granulocyte-rich populations by discontinuous Percoll density
      gradient centrifugation. Unexpectedly, bulk cells, but not the lymphocyte- or
      macrophage-rich populations, produced significant amounts of IL-4, IgE, and IgG;
      whereas production was restored by addition of Mac-1(+)  cells from the
      macrophage-rich to the lymphocyte-rich fraction. Furthermore, a combination of
      the lymphocyte-rich population (for IgG [or IgE]) production) and the macrophage
      rich population (for IgE [or IgG]) production) produced a large amount of IgE (or
      IgG). These results indicate that, in the initiation of allergic rhinitis,
      macrophages in the submandibular lymph nodes are essential not only for IL-4 or
      immunoglobulin production, but also for class switching of immunoglobulin in
      lymphocytes.

PMID- 22404752
TI  - Consumer response to healthy eating, physical activity and weight-related
      recommendations: a systematic review.
AB  - Strong evidence linking poor diet and lack of physical activity to risk of
      obesity and related chronic disease has supported the development and promotion
      of guidelines to improve population health. Still, obesity continues to escalate
      as a major health concern, and so the impact of weight-related guidelines on
      behaviour is unclear. The aim of this review was to examine consumer response to
      weight-related guidelines. A systematic literature search was performed using
      Medline, PsycInfo, ProQuest Central and additional searches using Google and
      reference lists. Of the 1,765 articles identified, 46 relevant titles were
      included. Most studies examined attitudes towards content, source, tailoring and
      comprehension of dietary guidelines. Many respondents reported that guidelines
      were confusing, and that simple, clear, specific, realistic, and in some cases,
      tailored guidelines are required. Recognition of guidelines did not signify
      understanding nor did perceived credibility of a source guarantee utilization of
      guidelines. There was a lack of studies assessing: the impact of guidelines on
      behaviour; responses to physical activity guidelines; responses among males and
      studies undertaken in developing countries. Further research is needed, in
      particular regarding responses to physical activity guidelines and guidelines in
      different populations. Communication professionals should assist health
      professionals in the development of accurate and effective weight-related
      guidelines.

PMID- 22404753
TI  - Insight into the dinuclear {Fe(NO)2}10{Fe(NO)2}10 and mononuclear {Fe(NO)2}10
      dinitrosyliron complexes.
AB  - The reversible redox transformations [(NO)(2)Fe(S(t)Bu)(2)](-) ? [Fe(MU
      S(t)Bu)(NO)(2)](2)(2-) ? [Fe(MU-S(t)Bu)(NO)(2)](2)(-) ? [Fe(MU-S(t)Bu)(NO)(2)](2)
      and [cation][(NO)(2)Fe(SEt)(2)] ? [cation](2)[(NO)(2)Fe(SEt)(2)] (cation = K(+)
      18-crown-6 ether) are demonstrated. The countercation of the {Fe(NO)(2)}(9)
      dinitrosyliron complexes (DNICs) functions to control the formation of the
      {Fe(NO)(2)}(10){Fe(NO)(2)}(10) dianionic reduced Roussin's red ester (RRE)
      [PPN](2)[Fe(MU-SR)(NO)(2)](2) or the {Fe(NO)(2)}(10) dianionic reduced monomeric
      DNIC [K(+)-18-crown-6 ether](2)[(NO)(2)Fe(SR)(2)] upon reduction of the
      {Fe(NO)(2)}(9) DNICs [cation][(NO)(2)Fe(SR)(2)] (cation = PPN(+), K(+)-18-crown-6
      ether; R = alkyl). The binding preference of ligands [OPh](-)/[SR](-) toward the
      {Fe(NO)(2)}(10){Fe(NO)(2)}(10) motif of dianionic reduced RRE follows the ligand
      displacement series [SR](-) > [OPh](-). Compared to the Fe K-edge preedge energy
      falling within the range of 7113.6-7113.8 eV for the dinuclear
      {Fe(NO)(2)}(9){Fe(NO)(2)}(9) DNICs and 7113.4-7113.8 eV for the mononuclear
      {Fe(NO)(2)}(9) DNICs, the {Fe(NO)(2)}(10) dianionic reduced monomeric DNICs and
      the {Fe(NO)(2)}(10){Fe(NO)(2)}(10) dianionic reduced RREs containing S/O/N
      ligation modes display the characteristic preedge energy 7113.1-7113.3 eV, which
      may be adopted to probe the formation of the EPR-silent {Fe(NO)(2)}(10)
      {Fe(NO)(2)}(10) dianionic reduced RREs and {Fe(NO)(2)}(10) dianionic reduced
      monomeric DNICs in biology. In addition to the characteristic Fe/S K-edge preedge
      energy, the IR nu(NO) spectra may also be adopted to characterize and
      discriminate [(NO)(2)Fe(MU-S(t)Bu)](2) [IR nu(NO) 1809 vw, 1778 s, 1753 s cm(-1)
      (KBr)], [Fe(MU-S(t)Bu)(NO)(2)](2)(-) [IR nu(NO) 1674 s, 1651 s cm(-1) (KBr)],
      [Fe(MU-S(t)Bu)(NO)(2)](2)(2-) [IR nu(NO) 1637 m, 1613 s, 1578 s, 1567 s cm(-1)
      (KBr)], and [K-18-crown-6 ether](2)[(NO)(2)Fe(SEt)(2)] [IR nu(NO) 1604 s, 1560 s
      cm(-1) (KBr)].

PMID- 22404754
TI  - Energy coupling in Saccharomyces cerevisiae: selected opportunities for metabolic
      engineering.
AB  - Free-energy (ATP) conservation during product formation is crucial for the
      maximum product yield that can be obtained, but often overlooked in metabolic
      engineering strategies. Product pathways that do not yield ATP or even demand
      input of free energy (ATP) require an additional pathway to supply the ATP needed
      for product formation, cellular maintenance, and/or growth. On the other hand,
      product pathways with a high ATP yield may result in excess biomass formation at
      the expense of the product yield. This mini-review discusses the importance of
      the ATP yield for product formation and presents several opportunities for
      engineering free-energy (ATP) conservation, with a focus on sugar-based product
      formation by Saccharomyces cerevisiae. These engineering opportunities are not
      limited to the metabolic flexibility within S. cerevisiae itself, but also
      expression of heterologous reactions will be taken into account. As such, the
      diversity in microbial sugar uptake and phosphorylation mechanisms, carboxylation
      reactions, product export, and the flexibility of oxidative phosphorylation via
      the respiratory chain and H(+) -ATP synthase can be used to increase or decrease
      free-energy (ATP) conservation. For product pathways with a negative, zero or too
      high ATP yield, analysis and metabolic engineering of the ATP yield of product
      formation will provide a promising strategy to increase the product yield and
      simplify process conditions.

PMID- 22404755
TI  - The United States Trypanosoma cruzi Infection Study: evidence for vector-borne
      transmission of the parasite that causes Chagas disease among United States blood
      donors.
AB  - BACKGROUND: Screening US blood donors for Trypanosoma cruzi infection is
      identifying autochthonous, chronic infections. Two donors in Mississippi were
      identified through screening and investigated as probable domestically acquired
      vector-borne infections, and the US T. cruzi Infection Study was conducted to
      evaluate the burden of and describe putative risk factors for vector-borne
      infection in the United States. STUDY DESIGN AND METHODS: Blood donors who tested
      enzyme-linked immunosorbent assay repeat reactive and positive by
      radioimmunoprecipitation assay, and whose mode of infection could not be
      identified, were evaluated with a questionnaire to identify possible sources of
      infection and by additional serologic and hemoculture testing for T. cruzi
      infection. RESULTS: Of 54 eligible donors, 37 (69%) enrolled in the study.
      Fifteen (41%) enrollees had four or more positive serologic tests and were
      considered positive for T. cruzi infection; one was hemoculture positive. Of the
      15, three (20%) donors had visited a rural area of an endemic country, although
      none had stayed for 2 or more weeks. All had lived in a state with documented T.
      cruzi vector(s) or infected mammalian reservoir(s), 13 (87%) reported outdoor
      leisure or work activities, and 11 (73%) reported seeing wild reservoir animals
      on their property. CONCLUSION: This report adds 16 cases, including one from the
      Mississippi investigation, of chronic T. cruzi infection presumably acquired via
      vector-borne transmission in the United States to the previously reported seven
      cases. The estimated prevalence of autochthonous infections based on this study
      is 1 in 354,000 donors. Determining US foci of vector-borne transmission is
      needed to better assess risk for infection.

PMID- 22404756
TI  - Maternal lipids at mid-pregnancy and the risk of preterm delivery.
AB  - OBJECTIVE: This study examined associations between maternal lipid levels at mid
      pregnancy and preterm delivery, medically indicated or spontaneous. DESIGN:
      Prospective cohort study. SETTING: Women were recruited from 52 clinics in five
      Michigan, USA communities (1998-2004). POPULATION: Pregnant women were enrolled
      at 15-27 weeks' gestation and followed to delivery (n=3019). METHODS: A single
      blood sample was obtained at study enrollment. Blood lipids, i.e. total
      cholesterol (TC), high-density lipoprotein (HDLc), low-density lipoprotein (LDLc)
      cholesterol, and triglycerides (TG), were measured on a sub-cohort (n=1309). MAIN
      OUTCOME MEASURES: There were 221 spontaneous, 100 medically indicated preterm
      deliveries and 988 term deliveries. Polytomous logistic regression models
      examined relationships among cholesterol levels (Low: <10(th) percentile,
      Referent: 10(th) -<70(th) percentile, High: >=70(th) percentile), quartiles of TG
      (Referent: first quartile) and delivery outcome (Referent: term). RESULTS: Odds
      of medically indicated preterm delivery were increased among women with low TC
      (adjusted odds ratio (aOR)=2.04, 95% confidence interval (CI): 1.12, 3.72), low
      HDLc (aOR=1.89, 95%CI: 1.04, 3.42) or low LDLc (aOR=1.96, 95%CI: 1.09, 3.54).
      Odds of spontaneous preterm delivery were increased among women with high TC
      (aOR=1.51, 95%CI: 1.06, 2.15), high LDLc (aOR=1.42, 95%CI: 0.99, 2.04) or high TG
      (aOR=1.90, 95%CI: 1.21, 2.97 and aOR=1.72, 95%CI: 1.06, 2.78 for third and fourth
      quartiles, respectively). CONCLUSIONS: Extremely low TC, HDLc, and LDLc were
      associated with a modest increase in risk of medically indicated preterm
      delivery, whereas high TC, LDLc and TG modestly increased the risk of spontaneous
      preterm delivery. Further research is needed to uncover explanations for these
      associations and to identify optimal ranges for maternal lipids.

PMID- 22404757
TI  - Significance of epithelial growth factor in the epithelial-mesenchymal transition
      of human gallbladder cancer cells.
AB  - Five gallbladder cancer (GBC) cell lines were examined for morphological changes
      in collagen gel culture. GBh3 and HUCCT-1 cells formed tubules in response to
      treatment with epithelial growth factor (EGF) and hepatocyte growth factor (HGF),
      and showed high levels of expression of E-cadherin (ECD), and low levels of
      SNAIL, vimentin, transforming growth factor (TGF)-beta, and nucleostemin (NS). In
      contrast, the GBd15 and FU-GBC-1 cell lines treated with EGF and HGF showed a
      scattering phenotype, and expressed low levels of ECD and high levels of SNAIL,
      vimentin, TGF-beta, and NS. All cell lines expressed the EGF receptor, c-Met,
      EGF, and TGF-alpha, but not HGF. Transforming growth factor-beta was upregulated
      by EGF. Knockdown of the EGF receptor abrogated both tubule formation and
      scattering, whereas KD of TGF-beta abrogated only scattering. Knockdown of EGF
      induced nuclear translocation of beta-catenin and Wnt-related NS induction in the
      scattering cell lines, but not in the tubule-forming cell lines, whereas KD of
      glycogen synthase kinase-3beta in the tubule-forming cell lines resulted in the
      nuclear translocation of beta-catenin and Wnt-related NS induction in response to
      EGF treatment. These results suggest that EGF enhances epithelial-mesenchymal
      transformation and acquisition of stemness in GBC cells with a scattering
      phenotype through the activity of beta-catenin. Repression of ECD in scattering
      GBC cells induced the release of beta-catenin from the cell adhesion complexes
      along the plasma membrane and its translocation to the nucleus to activate Wnt
      signaling, which upregulated NS.

PMID- 22404758
TI  - A practical guide for the use of boceprevir and telaprevir for the treatment of
      hepatitis C.
AB  - The aim of this study is to review clinical trial data on the newly approved
      protease inhibitors boceprevir and telaprevir to develop consensus
      recommendations on the optimal use of these agents for the treatment of patients
      with chronic hepatitis C virus (HCV) infection. An expert panel of seven leading
      authorities in viral hepatitis was convened to establish and disseminate a
      practical guide on best practices for incorporating boceprevir and telaprevir
      into therapy for HCV infection in both treatment-naive and treatment-experienced
      patients. The topics covered include selecting candidates for boceprevir- or
      telaprevir-based treatments, predictors of response and early viral kinetics,
      response-guided therapy approaches, on-treatment management strategies to
      optimize the likelihood of response and minimize the risk of drug resistance,
      management of adverse effects during therapy and key considerations for special
      populations. The expert panel incorporated the best available clinical evidence
      into recommendations on how boceprevir and telaprevir should be used in the
      clinical setting. They indicated how treatment regimens may differ according to
      the baseline factors, such as presence of cirrhosis and when therapy may need to
      be modified or stopped altogether because of adverse events or poor virologic
      response. This practical guide will serve as a valuable resource for clinicians
      embarking on the new treatment paradigm of boceprevir or telaprevir in
      combination with peginterferon/ribavirin for chronic genotype 1 HCV infection.

PMID- 22404759
TI  - Acute and long-term Purkinje cell loss following a single ethanol binge during
      the early third trimester equivalent in the rat.
AB  - BACKGROUND: In the rat, binge-like ethanol (EtOH) exposure during the early
      neonatal period (a developmental period equivalent to the human third trimester)
      can result in a permanent deficit of cerebellar Purkinje cells (Pcells). However,
      the consequences of a moderate binge alcohol exposure on a single day during this
      postnatal period have not been established. This is an issue of importance as
      many pregnant women binge drink periodically at social drinking levels. This
      study aimed to identify both the acute and long-term effects of exposure to a
      single alcohol binge that achieved a mean peak blood EtOH concentration of
      approximately 250 mg/dl during early postnatal life using a rat model of fetal
      alcohol spectrum disorders. METHODS: Acute apoptotic Pcell death 10 hours after a
      moderate dose binge EtOH exposure from postnatal days (PDs) 0 to 10 was assessed
      using active caspase-3 immunolabeling. Acute Pcell apoptosis was quantified in
      cerebellar vermal lobules I-X using the physical disector method. Long-term
      effects were assessed at PD 60 using stereological methods to determine total
      Pcell numbers in the vermis, lobule III, and lobule IX, following a moderate dose
      binge EtOH exposure at PDs 0, 2, or 4. RESULTS: Acute apoptosis was induced by
      EtOH on PDs 1 to 8 in a time and lobular-dependent manner. For EtOH exposure on
      PD 2, significant long-term Pcell loss occurred in lobule III. EtOH exposure on
      PD 4 resulted in significant long-term Pcell loss throughout the entire vermis.
      CONCLUSIONS: These results indicate that a single, early EtOH episode of moderate
      dose can create significant and permanent Pcell loss in the developing
      cerebellum.

PMID- 22404760
TI  - Splenic laceration: an unusual complication of ventriculoperitoneal shunt.
AB  - Ventriculoperitoneal shunt is a commonly performed procedure. Associated
      complications have been well described in the literature. This is the first case
      report of a splenic laceration caused by the distal catheter looping around the
      spleen, requiring a splenectomy. Careful study of pre-operative imaging is
      recommended in cases where intraabdominal injury is suspected.

PMID- 22404761
TI  - Is there a role for vagus nerve stimulation therapy as a treatment of traumatic
      brain injury?
AB  - This paper aims to review the current literature on vagus nerve stimulation (VNS)
      use in animal models of traumatic brain injury (TBI) and explore its potential
      role in treatment of human TBI. A MEDLINE search yielded four primary papers from
      the same group that demonstrated VNS mediated improvement following fluid
      percussion models of TBI in rats, seen as motor and cognitive improvements,
      reduction of cortical oedema and neuroprotective effects. The underlying
      mechanisms are elusive and authors attribute these to attenuation of post
      traumatic seizures, a noradrenergic mechanism and as yet undetermined mechanisms.
      Reviewing and elaborating on these ideas, we speculate other potential mechanisms
      including attenuation of peri-infarct depolarisations, attenuation of glutamate
      mediated excitotoxicity, stabilisation of intracranial pressure, enhancement of
      synaptic plasticity, upregulation of endogenous neurogenesis and anti
      inflammatory effects may have a role. Although this data unequivocally shows that
      VNS improves outcome from TBI in animal models, it remains to be determined if
      these findings translate clinically. Further studies are warranted.

PMID- 22404762
TI  - What paediatricians should know about eating disorders in children and young
      people.
AB  - Any health professional working with children and young people may become
      involved in the care of a child or young person with an eating disorder.
      Morbidity and mortality can be high, and paediatricians have an important role to
      play. There are broadly two aspects of underweight that the paediatrician may
      face - acute medical instability and a more chronic underweight which can impact
      greatly upon growth and development. Ultimate weight restoration means an
      adequate nutritional status to allow appropriate growth and development. Key to
      success is a team approach with paediatric and mental health and dietetic
      expertise combined. This paper provides an overview of eating disorders and
      explores current best practice, written in collaboration by a paediatrician and
      child and adolescent psychiatrist.

PMID- 22404763
TI  - The disparity between patient and nurse symptom rating in a hospice population.
AB  - BACKGROUND: Meticulous assessment, monitoring, and treatment of symptoms are key
      components of palliative care. The Symptom Assessment Scale (SAS) is a 0-10
      numerical rating scale (NRS) used for self-report of sleep, appetite, nausea,
      bowels, breathing, fatigue, and pain. Ideally, symptom rating should be by self
      report; however, the ratings are often completed by nurses. The aim of this study
      was to examine the relationship between simultaneous symptom ratings of patients
      and nurses in an Australian inpatient palliative care unit. METHODS: All
      inpatients and their treating nurse (blinded to the patient's report) scored the
      SAS weekly. Nurse symptom rating was considered accurate if the score for an
      individual symptom differed by <=1. The relationship for each dyad was examined
      by comparing absolute values, mean differences, and Pearson correlations.
      RESULTS: Sixty-four pairs of symptom ratings were obtained from 29 patients (mean
      65 years, male 55%, malignancy 90%, mean Karnofsky 50). The absolute differences
      were closest for nausea, bowels, and breathing domains, and worst for appetite.
      Mean differences and Pearson correlations did not adequately reflect the
      disparity between patient and nurse symptom rating, and nurses systematically
      underreported symptoms. The total difference for the seven items ranged from
      nurses overreporting the patients' symptoms by 39 points to underreporting by 31
      out of a possible 70 points. DISCUSSION: Proxy symptom assessment only modestly
      correlates with patient symptom rating, can significantly misrepresent the
      patient's actual symptom burden, and should only be used when the patient is
      absolutely unable to contribute his or her own view.

PMID- 22404764
TI  - Maternal warming affects early life stages of an invasive thistle.
AB  - Maternal environment can influence plant offspring performance. Understanding
      maternal environmental effects will help to bridge a key gap in the knowledge of
      plant life cycles, and provide important insights for species' responses under
      climate change. Here we show that maternal warming significantly affected the
      early life stages of an invasive thistle, Carduus nutans. Seeds produced by
      plants grown in warmed conditions had higher germination percentages and shorter
      mean germination times than those produced by plants under ambient conditions;
      this difference was most evident at suboptimal germination temperatures.
      Subsequent seedling emergence was also faster with maternal warming, with no cost
      to seedling emergence percentage and seedling growth. Our results suggest that
      maternal warming may accelerate the life cycle of this species via enhanced early
      life-history stages. These maternal effects on offspring performance, together
      with the positive responses of the maternal generation, may exacerbate invasions
      of this species under climate change. 

PMID- 22404765
TI  - The influence of the HLA-DRB1 and HLA-DQB1 allele heterogeneity on disease risk
      and severity in Iranian patients with multiple sclerosis.
AB  - Multiple sclerosis (MS) is a common autoimmune disorder of the central nervous
      system. Recent studies have shown that the HLA-DRB1 and DQB1 alleles are
      associated with MS susceptibility and severity. However, this is controversial in
      different population studies. In the present study, the roles of HLA-DRB1 and
      DQB1 alleles and the amino acids were investigated on disease risk and severity
      in 120 Iranian patients with MS and 120 controls. Our findings indicate that the
      DRB1*1501 allele (OR = 3.203 P = 0.001), the DRB1*1501-DQB1*0602 haplotype (OR =
      7.792 P = 0.003) and the DRB1*1501/0701- genotype (OR = 3.320 P = 0.006) and
      amino acid Leu26 (OR = 1.645 P = 0.005) and Phe9 (OR = 1.893 P = 0.009) on the
      DQbeta1 chain are significantly associated with MS susceptibility. DRB1*1001 was
      the only allele that had a protective effect against MS (P = 0.0004). We also
      found that the DQB1*0303 allele was significantly associated with disease
      severity (mean Multiple Sclerosis Severity Score difference = 1.979, P = 0.002).
      However, protective effect of the DRB1*1001 against MS and also association of
      DQB1*0303 allele with MS severity need to be confirmed by larger sample size.

PMID- 22404766
TI  - Kynurenines: from the perspective of major psychiatric disorders.
AB  - Psychiatric disorders are documented to be associated with a mild pro
      inflammatory state. Pro-inflammatory mediators could activate the tryptophan
      breakdown and kynurenine pathway with a shift toward the neurotoxic arm where
      excitotoxic N-methyl-D-aspartate receptor agonist quinolinic acid is formed. An
      unbalanced metabolism in terms of neuroprotective and neurotoxic effects, such as
      reduced kynurenic acid to kynurenine ratio, has been demonstrated in the major
      psychiatric disorders such as unipolar depression, bipolar manic-depressive
      disorder and schizophrenia, and in drug-induced neuropsychiatric side effects
      such as interferon-alpha treated patients. The changes in serum or plasma are
      shown to be associated with central changes such as in the cerebrospinal fluid
      and certain brain areas. While currently available antidepressants and mood
      stabilizers could not efficiently improve these neurochemical changes within the
      same period that could induce clinical improvement, some antipsychotic treatments
      could reverse certain metabolic imbalances. Some of these changes were tested
      also in animal models. In this review the role of this unbalanced kynurenine
      metabolism through interactions with other neurochemicals is discussed as a major
      contributing pathophysiological mechanism in psychiatric disorders. Moreover, the
      biomarker role of kynurenine metabolites and future therapeutic opportunities are
      also discussed.

PMID- 22404767
TI  - Vaccination coverage among medical residents in Paris, France.
AB  - Medical residents are particularly exposed to the risk of occupational infection.
      We aimed to determine the vaccination coverage in residents with an anonymous
      self-reporting electronic questionnaire. A total of 250 residents took part in
      this survey. Vaccination rates were particularly high for mandatory vaccinations
      (diphtheria, tetanus, poliomyelitis, hepatitis B virus and tuberculosis).
      Regarding recommended vaccinations (influenza, 45.6%; pertussis, 65.2%; measles,
      62.8%; varicella, 62.8%), rates were insufficient to prevent hospital epidemics,
      but higher than those reported in other healthcare workers. Further immunization
      programmes should target residents, and not only senior healthcare workers, with
      a critical role for occupational medicine departments.

PMID- 22404768
TI  - Sensorimotor cortical activation in patients with sleep bruxism.
AB  - Sleep bruxism is assumed to be triggered by a dysfunctional subcortical and
      cortical network. This study investigates sensorimotor cortical activation in
      patients with sleep bruxism during clenching and chewing. Nine
      polysomnographically diagnosed patients and nine healthy control subjects
      underwent magnetoencephalography (MEG). During clenching and chewing, patients
      with bruxism revealed significantly larger event-related desynchronization in the
      somatomotor area (Brodmann area 4) than healthy subjects. Group differences in
      the muscle activity were ruled out by electromyography (EMG) assessments during
      MEG. This result might be regarded as a consequence of increased sensorimotor
      cortical representation of the tongue and chewing musculature due to an enhanced
      parafunctional muscle activity in bruxers potentially triggered by occlusal
      factors. Alternatively, a secondary activation of cortical structures during
      sleep bruxism in the context of an activated network of subcortical and cortical
      structures might lead to increased cortical representation of the chewing
      musculature via use dependent plasticity.

PMID- 22404769
TI  - Biotechnological, genomics and systems-synthetic biology revolution: redesigning
      genetic code for a pragmatic systems medicine.

PMID- 22404771
TI  - Randomized controlled trial evaluating participation and yield of colonoscopy
      versus CT colonography screening.
AB  - Colorectal cancer is a common yet preventable condition. Population screening
      attempts suffer from a lack of widespread participation with the currently
      available options. Computerized tomography colonography (CTC) represents a
      promising addition to the screening armamentarium. CTC is less invasive than
      optical colonoscopy but has been shown to be equivalent to colonoscopy for the
      detection of advanced neoplasia, which represents the primary target of screening
      and prevention. Although CTC has generally been preferred over colonoscopy by
      patients in most published studies, little hard evidence exists regarding the
      level of increase in screening participation related to CTC. The landmark trial
      under discussion adds key data in terms of participation rates for CTC screening
      relative to colonoscopy screening.

PMID- 22404772
TI  - Recombinant human PDGF-BB in foot and ankle fusion.
AB  - Autogenous bone graft (autograft) is currently the gold standard for augmenting
      bone repair and fusion procedures of the foot and ankle. The time, cost and
      morbidity involved in obtaining autograft, however, are well documented and
      legitimate concerns remain surrounding this intervention. Endogenous human PDGF
      is chemotactic and mitogenic for osteoblasts and undifferentiated osteoprogenitor
      cells, and upregulates expression of cytokines necessary for osseous and soft
      tissue healing and regeneration. The BB isoform of PDGF, and the biosynthetic
      replica recombinant human PDGF-BB, is a key regulatory molecule in bone
      homeostasis, repair and regeneration. When combined with a beta-tricalcium
      phosphate osteoconductive matrix, recombinant human PDGF-BB mitigates a number of
      problems associated with the use of autograft and, based on its preclinical
      performance and early clinical success, appears to be an equally effective and
      perhaps an even safer alternative to autograft for foot and ankle fusion
      (arthrodesis) procedures.

PMID- 22404773
TI  - Covered-stent implantation to treat aortic coarctation.
AB  - Aortic coarctation comprises approximately 7% of all known congenital heart
      defects. Surgery and balloon angioplasty have been performed for many years but
      are associated with a significant incidence of recoarctation and aneurysm
      formation. Although bare-stent implantation decreases the incidence of
      recoarctation, the risk of aortic dissection or aneurysm formation is not
      eliminated. Described initially to treat patients with coexistent aneurysm of the
      aortic wall, we currently believe that covered-stent implantation for aortic
      coarctation should play a more important role. Our increasing experience from
      expanding their indication to deal with complications from previous
      interventions, associated defects or particular anatomical situations has led us
      to conclude that most of cases of aortic coarctation in adolescents and adults
      should be treated by the implantation of covered stents.

PMID- 22404774
TI  - Functional mitral regurgitation: modern concepts for ventricular geometry
      reshaping.
AB  - Functional mitral valve regurgitation (MR), a condition affecting millions of
      primarily elderly patients worldwide, is associated with poor clinical outcomes.
      Functional MR has traditionally been considered a disorder of regional or global
      left ventricular (LV) remodeling secondary to myocardial disease, in which
      anatomically normal leaflets fail to coapt adequately. The primary mechanisms of
      MR are mitral annular dilatation and leaflet restriction secondary to LV
      remodeling. Although annuloplasty is commonly used to correct valve incompetence,
      the effects of altered ventricular mechanics on MR need to be specifically
      addressed. This review focuses on current concepts of geometric reconfiguration
      of the LV and mitral-ventricular apparatus to reduce MR.

PMID- 22404775
TI  - MRI in patients with cardiac implantable electronic devices.
AB  - MRI is a powerful diagnostic tool; however, it is relatively contraindicated for
      patients with cardiovascular implantable electronic devices (CIEDs) such as
      pacemakers and implantable defibrillators. Several interactions with CIEDs have
      the potential to cause harm, and fatalities have been reported. Limited
      experience of MRI in patients with CIEDs under close supervision and utilizing
      specific scanning protocols has emerged from a small number of centers. Even
      then, adverse effects on the CIED have been reported. The recent development of
      MRI-conditional pacemaker systems and the demonstration of safe magnetic
      resonance scanning in a large clinical trial (EnRhythm MRI SureScan Pacing System
      Study) is a significant advance in the care of patients with CIEDs, opening up
      this important imaging modality to those previously denied it. Further
      development of MRI-conditional CIEDs, including implantable cardioverter
      defibrillators, is expected but presents many technological challenges.

PMID- 22404776
TI  - All-inside meniscal repair devices and techniques.
AB  - Techniques and devices for meniscal repair are evolving, including for all-inside
      meniscal repair. The first-generation all-inside meniscal repair devices were
      simplistic in design, but their technical difficulties and risks led to the
      development of second-generation devices. These devices employed the suture
      anchor concept for repair and confirmed the safety of use through standard
      anterior arthroscopic portals. Third-generation devices introduced the idea of
      rigid, bioabsorbable materials; unfortunately, these demonstrated higher failure
      and complication rates compared with other repair techniques. They were also
      limited in their ability to adjust compression and tension across the repair.
      Now, fourth-generation devices have been developed that are flexible, suture
      based, and allow for variable compression and retensioning across the tear. Each
      device has its own specifications and technical nuances. With a comprehensive
      understanding of the current devices available, the industry and surgeons may
      continue in the development of safer, more successful, user-friendly and cost
      effective all-inside devices.

PMID- 22404777
TI  - Prosthetic mesh materials used in hernia surgery.
AB  - It is estimated that 20 million prosthetic meshes are implanted each year
      worldwide. It is clear that the evolution of meshes is not yet complete and the
      ideal mesh is yet to be found. There is a vast array of prosthetics available for
      hernia repair. This review outlines the properties of available meshes and the
      evidence to be considered when choosing a prosthetic for hernia repair.

PMID- 22404778
TI  - Emerging roles for biomaterials in the treatment of liver disease.
AB  - This review explores potential roles for biomaterials in the field of liver
      surgery and hepatology. The studies reviewed are presented in three sections. The
      first section discusses liver regeneration and strategies to modulate it. The
      second section outlines the pathophysiology of liver inflammation and fibrosis
      and highlights novel therapeutic targets. The final section summarises the
      current challenges in liver surgery and discusses how biomaterials may be used to
      address these challenges and focuses on early translational applications for
      biomaterials for drug delivery and liver surgery.

PMID- 22404779
TI  - Subthreshold diode laser micropulse photocoagulation for the treatment of
      diabetic macular edema.
AB  - Diabetic macular edema (DME) is a sight-threatening complication of diabetic
      retinopathy, the leading cause of visual loss in the working-age population in
      the industrialized and emerging world. The standard of care for DME is focal/grid
      laser photocoagulation, which is proven effective in reducing the risk of vision
      loss, but inherently destructive and associated with tissue damage and collateral
      effects. Subthreshold diode laser micropulse photocoagulation is a nondestructive
      tissue-sparing laser procedure, which, in randomized controlled trials for the
      treatment of DME, has been found equally effective as conventional
      photocoagulation. Functional and anatomical outcomes from four independent
      randomized controlled trials provide level one evidence that vision
      stabilization/improvement and edema resolution/reduction can be elicited with
      less or no retinal damage, and with fewer or no complications. This review
      describes the principles of subthreshold diode laser micropulse photocoagulation,
      its treatment modalities and clinical outcomes in the context of standard laser
      treatments and of emerging nonlaser therapies for DME.

PMID- 22404781
TI  - Low genetic diversity and local adaptive divergence of Dracaena cambodiana
      (Liliaceae) populations associated with historical population bottlenecks and
      natural selection: an endangered long-lived tree endemic to Hainan Island, China.
AB  - Historical population bottlenecks and natural selection have important effects on
      the current genetic diversity and structure of long-lived trees. Dracaena
      cambodiana is an endangered, long-lived tree endemic to Hainan Island, China. Our
      field investigations showed that only 10 populations remain on Hainan Island and
      that almost all have been seriously isolated and grow in distinct habitats. A
      considerable amount of genetic variation at the species level, but little
      variation at the population level, and a high level of genetic differentiation
      among the populations with limited gene flow in D. cambodiana were detected using
      inter-simple sequence repeat (ISSR) and random amplified polymorphic DNA (RAPD)
      analyses. No significant correlation was found between genetic diversity and
      actual population size, as the genetic diversities were similar regardless of
      population size. The Mantel test revealed that there was no correlation between
      genetic and geographic distances among the 10 populations. The UPGMA, PCoA and
      Bayesian analyses showed that local adaptive divergence has occurred among the D.
      cambodiana populations, which was further supported by habitat-private fragments.
      We suggest that the current genetic diversity and population differentiation of
      D. cambodiana resulted from historical population bottlenecks and natural
      selection followed by historical isolation. However, the lack of natural
      regeneration of D. cambodiana indicates that former local adaptations with low
      genetic diversity may have been genetically weak and are unable to adapt to the
      current ecological environments. 

PMID- 22404782
TI  - Experience of child and adolescent mental health clinicians working within an at
      risk mental state for psychosis service: a qualitative study.
AB  - AIM: To qualitatively examine the common experiences of child and adolescent
      mental health clinicians working with adolescents suspected of having an 'at-risk
      mental state' (ARMS) for psychosis. METHODS: A semistructured interview was
      conducted with six experienced child and adolescent mental health clinicians
      working in North East England. RESULTS: A thematic analysis of clinicians'
      experiences indicated that the identification and management of an ARMS within
      this patient group is particularly complex. In terms of treatment options,
      approaches that promoted social inclusion were favoured, but the use of
      antipsychotic medication was perceived as a 'last resort', requiring serious
      consideration. Clear guidelines and an overall consensus were judged to be
      lacking in terms of coordinating care and multi-agency working practices.
      CONCLUSIONS: Establishing a formalized care pathway that also incorporates
      regular training and supervision may be required by this and other clinical
      services working with adolescents suspected of having an ARMS. Improved
      identification, a firmer evidence base regarding treatment practices and clear
      guidelines are required for this age group. This need will become more urgent
      should a psychosis risk syndrome be included as a diagnostic category in the
      Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V).

PMID- 22404783
TI  - Design, synthesis, and initial biological evaluation of a steroidal anti-estrogen
      doxorubicin bioconjugate for targeting estrogen receptor-positive breast cancer
      cells.
AB  - As part of our program to develop breast cancer specific therapeutic agents, we
      have synthesized a conjugate agent that is a conjugate of the steroidal anti
      estrogen and the potent cytotoxin doxorubicin. In this effort, we employed a
      modular assembly approach to prepare a novel 11beta-substituted steroidal anti
      estrogen functionalized with an azido-tetraethylene glycol moiety, which could be
      coupled to a complementary doxorubicin benzoyl hydrazone functionalized with a
      propargyl tetraethylene glycol moiety. Huisgen [3 + 2] cycloaddition chemistry
      gave the final hybrid that was evaluated for selective uptake and cytotoxicity in
      ER(+)-MCF-7 and ER(-)-MDA-MB-231 breast cancer cell lines. The results
      demonstrated that the presence of the anti-estrogenic component in the hybrid
      compound was critical for selectivity and cytotoxicity in ER(+)-MCF-7 human
      breast cancer cells as the hybrid was ~70-fold more potent than doxorubicin in
      inhibition of cell proliferation and promoting cell death.

PMID- 22404785
TI  - Biological activities of nitidine, a potential anti-malarial lead compound.
AB  - BACKGROUND: Nitidine is thought to be the main active ingredient in several
      traditional anti-malarial remedies used in different parts of the world. The
      widespread use of these therapies stresses the importance of studying this
      molecule in the context of malaria control. However, little is known about its
      potential as an anti-plasmodial drug, as well as its mechanism of action.
      METHODS: In this study, the anti-malarial potential of nitidine was evaluated in
      vitro on CQ-sensitive and -resistant strains. The nitidine's selectivity index
      compared with cancerous and non-cancerous cell lines was then determined. In vivo
      assays were then performed, using the four-day Peter's test methodology. To gain
      information about nitidine's possible mode of action, its moment of action on the
      parasite cell cycle was studied, and its localization inside the parasite was
      determined using confocal microscopy. The in vitro abilities of nitidine to bind
      haem and to inhibit beta-haematin formation were also demonstrated. RESULTS:
      Nitidine showed similar in vitro activity in CQ-sensitive and resistant strains,
      and also a satisfying selectivity index (> 10) when compared with a non-cancerous
      cells line. Its in vivo activity was moderate; however, no sign of acute toxicity
      was observed during treatment. Nitidine's moment of action on the parasite cycle
      showed that it could not interfere with DNA replication; this was consistent with
      the observation that nitidine did not localize in the nucleus, but rather in the
      cytoplasm of the parasite. Nitidine was able to form a 1-1 complex with haem in
      vitro and also inhibited beta-haematin formation with the same potency as
      chloroquine. CONCLUSION: Nitidine can be considered a potential anti-malarial
      lead compound. Its ability to complex haem and inhibit beta-haematin formation
      suggests a mechanism of action similar to that of chloroquine. The anti-malarial
      activity of nitidine could therefore be improved by structural modification of
      this molecule to increase its penetration of the digestive vacuole in the
      parasite, where haemoglobin metabolization takes place.

PMID- 22404786
TI  - Generic phylogeny, historical biogeography and character evolution of the
      cosmopolitan aquatic plant family Hydrocharitaceae.
AB  - BACKGROUND: Hydrocharitaceae is a fully aquatic monocot family, consists of 18
      genera with approximately 120 species. The family includes both fresh and marine
      aquatics and exhibits great diversity in form and habit including annual and
      perennial life histories; submersed, partially submersed and floating leaf habits
      and linear to orbicular leaf shapes. The family has a cosmopolitan distribution
      and is well represented in the Tertiary fossil record in Europe. At present, the
      historical biogeography of the family is not well understood and the generic
      relationships remain controversial. In this study we investigated the phylogeny
      and biogeography of Hydrocharitaceae by integrating fossils and DNA sequences
      from eight genes. We also conducted ancestral state reconstruction for three
      morphological characters. RESULTS: Phylogenetic analyses produced a phylogeny
      with most branches strongly supported by bootstrap values greater than 95 and
      Bayesian posterior probability values of 1.0. Stratiotes is the first diverging
      lineage with the remaining genera in two clades, one clade consists of
      Lagarosiphon, Ottelia, Blyxa, Apalanthe, Elodea and Egeria; and the other
      consists of Hydrocharis-Limnobium, Thalassia, Enhalus, Halophila, Najas,
      Hydrilla, Vallisneria, Nechamandra and Maidenia. Biogeographic analyses (DIVA,
      Mesquite) and divergence time estimates (BEAST) resolved the most recent common
      ancestor of Hydrocharitaceae as being in Asia during the Late Cretaceous and
      Palaeocene (54.7-72.6 Ma). Dispersals (including long-distance dispersal and
      migrations through Tethys seaway and land bridges) probably played major roles in
      the intercontinental distribution of this family. Ancestral state reconstruction
      suggested that in Hydrocharitaceae evolution of dioecy is bidirectional, viz.,
      from dioecy to hermaphroditism, and from hermaphroditism to dioecy, and that the
      aerial-submerged leaf habit and short-linear leaf shape are the ancestral states.
      CONCLUSIONS: Our study has shed light on the previously controversial generic
      phylogeny of Hydrocharitaceae. The study has resolved the historical biogeography
      of this family and supported dispersal as the most likely explanation for the
      intercontinental distribution. We have also provided valuable information for
      understanding the evolution of breeding system and leaf phenotype in aquatic
      monocots.

PMID- 22404787
TI  - Evaluation of molecular breast imaging in women undergoing myocardial perfusion
      imaging with Tc-99m sestamibi.
AB  - BACKGROUND: Our objective was to explore the potential benefits of molecular
      breast imaging (MBI) as a screening technique in women undergoing stress
      myocardial perfusion studies. METHODS: MBI was offered to women receiving Tc-99m
      sestamibi injection for myocardial perfusion stress testing. During the required
      waiting period after stress isotope injection, MBI was performed using a
      dedicated breast imaging gamma camera system. MBI examinations were interpreted
      by breast radiologists, with review of a recent mammogram in cases with positive
      MBI. RESULTS: Of 322 women enrolled, 313 completed MBI, comprising 5 with known
      breast cancer, 2 with known high-risk benign breast lesions, and 306 who were
      asymptomatic for breast disease with a recent negative mammogram. Analysis was
      limited to the 306 patients with no known breast disease. MBI was positive in 22
      of 306, giving a recall rate of 7.2% (95% confidence interval [CI] 4.8-10.6]. MBI
      detected 4 new cancers, resulting in a supplemental diagnostic yield of 13.1/1000
      women screened (95% CI 5.1-33.2). The number of cancers diagnosed per abnormal
      MBI examinations (PPV(1)) was 18% (4 of 22) (95% CI 7.3-38.5), and the number
      diagnosed per MBI-prompted biopsies (PPV(3)) was 44% (4 of 9) (95% CI 18.9-73.3).
      CONCLUSIONS: The addition of MBI to clinically indicated stress myocardial
      perfusion imaging studies in women results in a high diagnostic yield of newly
      detected breast cancers while generating a low rate of additional unnecessary
      workup.

PMID- 22404788
TI  - Recognition, regulation, scope of practice: nurse practitioners' growing pains.

PMID- 22404789
TI  - Knowledge and attitudes of primary care physicians toward the nurse practitioner
      role in the Kingdom of Bahrain.
AB  - PURPOSE: The Kingdom of Bahrain is facing a number of challenges, including an
      escalating cost of health services, increasing incidence of chronic diseases, and
      shortage of primary care physicians (PCPs). Introducing the nurse practitioner
      (NP) specialty in the primary care setting is one way to meet these challenges.
      The purpose of this quasi-experimental study was to examine the knowledge and
      attitudes of PCPs about the NP role prior to and following an educational
      intervention. DATA SOURCES: The modified Northern Emergency Nurse Practitioner
      Staff Survey was used to measure the PCPs' attitudes and knowledge. A total of 90
      PCPs completed the pretest and posttest. CONCLUSIONS: The study findings showed
      that PCPs had poor understanding of the NP role. Their knowledge and attitudes
      changed significantly after the educational intervention. Also, posttest data
      indicated a positive correlation between knowledge and attitudes toward the NP
      role. IMPLICATIONS FOR PRACTICE: More educational preparation and orientation to
      the NP role for PCPs and other healthcare professionals are needed before the
      implementation of the role in the primary care setting in Bahrain. There is a
      need for the role to be clearly defined prior to implementation to help gain
      understanding and acceptance.

PMID- 22404790
TI  - Perceptions of NPs and administrators in regard to the governing and supervision
      of NPs in Taiwan.
AB  - PURPOSE: To determine the perceptions of nurse practitioners (NPs) and
      administrators in regard to the governing and supervision of NPs, using a
      qualitative approach. DATA SOURCES: The study used a qualitative research design,
      with 14 participants recruited through purposive sampling. Data were collected
      through a semi-structured interview and were analyzed through content analysis to
      identify the concepts and themes. CONCLUSIONS: NPs in Taiwan are challenged by a
      number of barriers; however, they remain positive that their circumstances will
      improve. IMPLICATIONS FOR PRACTICE: The results indicated that clinicians and
      hospital managers, including NPs themselves, need to have a solid understanding
      of NP regulations. Communication with other disciplines and policymakers is key
      to success in the NP role. This study provides valuable information for NPs,
      other healthcare professionals, and administrators in terms of promoting the role
      of NPs.

PMID- 22404791
TI  - Nurse practitioners in Taiwan: today and tomorrow.
AB  - PURPOSE: To describe the barriers that nurse practitioners (NPs) face and their
      hopes for the future. DATA SOURCES: The study used a qualitative research design,
      with 10 certified NPs who were recruited through convenience sampling. Data were
      collected through a face-to-face semi-structured interview, and content analysis
      was used to analyze the data. CONCLUSIONS: NPs in Taiwan are challenged by a
      number of barriers; however, they remain positive that their circumstances will
      improve. IMPLICATIONS FOR PRACTICE: The results of this study suggest that there
      is a need for better communication between policymakers and NPs. Additionally, as
      recommended by the International Council of Nursing, there is a need for NPs to
      earn a master's degree and to have formal training prior to beginning work as an
      NP. Furthermore, to evaluate the NPs' performance, outcome studies need to be
      conducted. Implementing such recommendations should enable NPs to earn the
      respect and support of healthcare professionals and administrators.

PMID- 22404792
TI  - National nursing registration in Australia: a way forward for nurse practitioner
      endorsement.
AB  - PURPOSE: The move to national registration of health professionals and the
      creation of the Nursing and Midwifery Board of Australia (NMBA) provides both
      challenges and opportunities for the regulation of nurse practitioners (NPs) in
      Australia. DATA SOURCES: National and state health policy documents, accessible
      on the Internet, concerning the regulation and endorsement processes for NPs in
      Australia were examined. CONCLUSIONS: The similarities between two of the
      previous jurisdictional NP endorsement processes in New South Wales and Victoria
      provide a common ground on which to build a robust national system. However,
      there are also key differences between these two states. These differences were
      mainly in the evidence required to assess competency of NP applicants and the
      authority to prescribe medications. All Victorian NP applicants were required to
      complete an approved medication subject at a master's level. IMPLICATIONS FOR
      PRACTICE: A consistent endorsement process that delivers NPs of the highest
      standard and allows for efficient use of their skills and expertise is vital.
      This needs to be performed with the aim of providing high-quality care in a
      regulatory environment that protects the public and clearly articulates the level
      of competence expected of all NPs.

PMID- 22404793
TI  - Outcomes from the evaluation of an emergency department-based mental health nurse
      practitioner outpatient service in Australia.
AB  - PURPOSE: To evaluate an emergency department (ED)-based mental health nurse
      practitioner (MHNP) outpatient service in Sydney, Australia. DATA SOURCES: Data
      collection incorporated waiting times for follow-up outpatient appointments, two
      brief self-report measures (the K-10 measure of psychological distress and the
      General Self-Efficacy Scale), a satisfaction tool, and interviews conducted with
      a random selection of outpatients and a stratified, purposive sample of ED staff.
      CONCLUSIONS: Over 60% of outpatients were followed up within 5 days of their
      initial presentation. The mean K-10 score at baseline was 32 (very high
      psychological distress, n = 101) but this had decreased by two categories to 24
      at follow-up (moderate psychological distress, n = 51). There was a modest
      association between decreased psychological distress and an increase in perceived
      self-efficacy. Participant satisfaction with aspects of the outpatient service
      was generally rated as high to very high. Interviewed outpatients (n = 23) were
      particularly positive about the accessibility, immediacy, and flexibility of the
      service and overall therapeutic benefits. Emergency staff (n = 20) considered the
      outpatient service enhanced service provision by facilitating access to a
      population of patients who were previously underserved. IMPLICATIONS FOR
      PRACTICE: The ED-based MHNP role enhances access to specialized mental health
      care and also supports emergency staff.

PMID- 22404794
TI  - Acute respiratory distress syndrome following scrub typhus: a case report.
AB  - PURPOSE: To discuss a case of scrub typhus complicated with acute respiratory
      distress syndrome (ARDS) in a 67-year-old female. An overview of the prevalence
      and pathogenesis of the disorder, clinical diagnosis, and treatment are
      presented. DATA SOURCES: Case report, diagnostic evidence, and scientific
      literature. CONCLUSIONS: If not properly treated, scrub typhus can cause serious
      complications, such as ARDS and septicemia. When left untreated, the mortality
      rate for scrub typhus will be increased. When there is a cause to believe that
      scrub typhus is present, doxycycline treatment leads to rapid symptom
      improvement. IMPLICATIONS FOR PRACTICE: People might not be aware of the
      possibility of scrub typhus because it had been a more common disease in the
      past. Nurse practitioners (NPs) should take a detail history and be aware of
      common clinical manifestations to promote the early recognition and appropriate
      treatment of scrub typhus, which would prevent severe complications and reduce
      mortality. A resurgence of the disease could occur at any time among military
      troops serving in endemic regions.

PMID- 22404795
TI  - Cyanobacterial life at low O(2): community genomics and function reveal metabolic
      versatility and extremely low diversity in a Great Lakes sinkhole mat.
AB  - Cyanobacteria are renowned as the mediators of Earth's oxygenation. However,
      little is known about the cyanobacterial communities that flourished under the
      low-O(2) conditions that characterized most of their evolutionary history.
      Microbial mats in the submerged Middle Island Sinkhole of Lake Huron provide
      opportunities to investigate cyanobacteria under such persistent low-O(2)
      conditions. Here, venting groundwater rich in sulfate and low in O(2) supports a
      unique benthic ecosystem of purple-colored cyanobacterial mats. Beneath the mat
      is a layer of carbonate that is enriched in calcite and to a lesser extent
      dolomite. In situ benthic metabolism chambers revealed that the mats are net
      sinks for O(2), suggesting primary production mechanisms other than oxygenic
      photosynthesis. Indeed, (14)C-bicarbonate uptake studies of autotrophic
      production show variable contributions from oxygenic and anoxygenic
      photosynthesis and chemosynthesis, presumably because of supply of sulfide. These
      results suggest the presence of either facultatively anoxygenic cyanobacteria or
      a mix of oxygenic/anoxygenic types of cyanobacteria. Shotgun metagenomic
      sequencing revealed a remarkably low-diversity mat community dominated by just
      one genotype most closely related to the cyanobacterium Phormidium autumnale, for
      which an essentially complete genome was reconstructed. Also recovered were
      partial genomes from a second genotype of Phormidium and several Oscillatoria.
      Despite the taxonomic simplicity, diverse cyanobacterial genes putatively
      involved in sulfur oxidation were identified, suggesting a diversity of sulfide
      physiologies. The dominant Phormidium genome reflects versatile metabolism and
      physiology that is specialized for a communal lifestyle under fluctuating redox
      conditions and light availability. Overall, this study provides genomic and
      physiologic insights into low-O(2) cyanobacterial mat ecosystems that played
      crucial geobiological roles over long stretches of Earth history.

PMID- 22404796
TI  - Pain originating from the sacroiliac joint is a common non-traumatic
      musculoskeletal complaint in elite inline-speedskaters - an observational study.
AB  - STUDY DESIGN: Observational study OBJECTIVES: To investigate common non-traumatic
      musculoskeletal complaints of the low back in elite inline-speedskaters of the
      German national team. SUMMARY OF BACKGROUND DATA: Traumatic injuries associated
      with falls or collisions are well documented in speedskaters but so far no
      studies have investigated non-traumatic low back pain. Previously, the sacroiliac
      joint was suspected as a frequent origin of complaint, we aimed to investigate
      this assumption. METHODS: Two chiropractors examined elite inline-speedskaters of
      the German national team during three sports events between summer 2010 and 2011.
      A test cluster of five provocative tests for the sacroiliac joint was selected
      based on reliability and validity. RESULTS: A total of 37 examinations were
      conducted on 34 athletes with low back pain during the three sport events. The
      reported pain intensities ranged from mild to moderate pain (VAS 23.4 +/- 13.4 to
      35.1 +/- 19.2). About 90% of cases showed involvement of the SI joint of which
      again 90% presented with left sided symptoms. CONCLUSIONS: Non-traumatic
      complaints of the low back originating from the left sacroiliac joint frequently
      occur in competitive inline speedskaters.

PMID- 22404797
TI  - Number of prior episodes and the presence of depressive symptoms are associated
      with longer length of stay for patients with acute manic episodes.
AB  - BACKGROUND: Few studies have analyzed predictors of length of stay (LOS) in
      patients admitted due to acute bipolar manic episodes. The purpose of the present
      study was to estimate LOS and to determine the potential sociodemographic and
      clinical risk factors associated with a longer hospitalization. Such information
      could be useful to identify those patients at high risk for long LOS and to
      allocate them to special treatments, with the aim of optimizing their hospital
      management. METHODS: This was a cross-sectional study recruiting adult patients
      with a diagnosis of bipolar disorder (Diagnostic and Statistical Manual of Mental
      Disorders, 4th edition, text revision (DSM-IV-TR) criteria) who had been
      hospitalized due to an acute manic episode with a Young Mania Rating Scale total
      score greater than 20. Bivariate correlational and multiple linear regression
      analyses were performed to identify independent predictors of LOS. RESULTS: A
      total of 235 patients from 44 centers were included in the study. The only
      factors that were significantly associated to LOS in the regression model were
      the number of previous episodes and the Montgomery-Asberg Depression Rating Scale
      (MADRS) total score at admission (P < 0.05). CONCLUSIONS: Patients with a high
      number of previous episodes and those with depressive symptoms during mania are
      more likely to stay longer in hospital. Patients with severe depressive symptoms
      may have a more severe or treatment-resistant course of the acute bipolar manic
      episode.

PMID- 22404799
TI  - Commercial scale research and assessment of poultry welfare.
AB  - 1. Commercial level research on poultry welfare is increasingly important because
      of the insight it gives into what improves welfare in the context of other
      important drivers such as human health, environmental impact and cost.   2. There
      are, however, a number of problems with conducting commercial level research -
      such as conflicts over aims, financial compensation and legal issues - that need
      to be addressed if the gains from commercial research are to be optimized.
      Cooperation between all parties and mutual understanding of the different
      priorities that may exist between industry and academia are essential.   3. Three
      important developments for the future are: the setting up of a 'data bank', the
      application of new statistical methods for analyzing data and new technology for
      assessing welfare automatically.

PMID- 22404798
TI  - Effectiveness of a cognitive-behavioral therapy (CBT) manualized program for
      clinically anxious children: study protocol of a randomized controlled trial.
AB  - BACKGROUND: In the Netherlands, the prevalence of anxiety disorders is 20%; and
      children with anxiety are at increased risk for psychopathology throughout
      adulthood. Recently, a revised version of a cognitive behavioral therapy
      manualized program called 'Thinking + Doing = Daring' (TDD) was developed for
      children between 8 and 12 years old with an anxiety disorder. The main aim of
      this project is to conduct a Randomized Controlled Trial (RCT) to evaluate the
      effectiveness of TDD. METHODS/DESIGN: The CBT program will be tested with a RCT
      with 120 clinically anxious children (8-12 years old) referred to one of three
      mental health care agencies. Children will be randomly assigned to the
      experimental (N = 60, TDD) or to the control condition (N = 60, treatment as
      usual). The primary outcome measure will be the child's anxiety symptoms level.
      Secondary outcome measures will be externalizing (e.g. aggression) and
      internalizing problems (e.g. depression). Two potential mediators of change will
      be examined in the current study: therapeutic alliance and parenting. Mother and
      child in both the experimental and control condition will be surveyed at
      baseline, post treatment and after 6 and 12 months (follow-up). It is
      hypothesized that children in the experimental condition will show a stronger
      decrease in anxiety symptoms compared to children that receive treatment as
      usual. Moreover, we expect that a strong therapeutic alliance and decreases in
      parental control and rejection will contribute to treatment success. DISCUSSION:
      Early treatment for anxiety problems has the potential to not only result in
      anxiety reductions, but also to prevent future problems such as substance abuse
      and psychopathology throughout adulthood. Our results will be immediately
      relevant to practice, since we are partnering with 'real world' community
      agencies. If the CBT program proves more effective than treatment as usual, it
      could be implemented in community mental health care agencies across the
      Netherlands and beyond. Moreover, it has the potential to make treatment in these
      community settings shorter, more efficient and therefore cost-effective. TRIAL
      REGISTRATION: Nederlands Trial Register NTR2967.

PMID- 22404800
TI  - Impact of daylength on the productivity of two commercial broiler strains.
AB  - 1. The impact of daylength on productivity in male and female broilers of two
      genotypes was studied in two replicated experiments. In each experiment, four
      lighting programs (14L:10D (14L), 17L:7D (17L), 20L:4D (20L) and 23L:1D (23L))
      were used to study the relationships between productivity and daylength in two
      genotypes and both genders.   2. General Linear Model analysis was used to test
      for differences in daylength, genotype, gender and their interactions, and
      regression analysis to define relationships between productivity and daylength in
      experiment one and daylength differences in experiment two.   3. In experiment
      one, body weights at d 32 (P = 0.002) and d 39 (P = 0.011) were related in a
      quadratic fashion to daylength, with the heaviest birds raised under 20L. The
      growth curve at d 49 was similar in shape, and body weights under both 17L and
      20L were significantly higher than under 14L and 23L (P < 0.001). In experiment
      two, data were similar, although the quadratic relationship was not significant. 
      4. Feed consumption was highest to d 39 or d 49 under 20L, and birds under 23L
      ate as much (d 39) or less feed (d 49) than under 17L.   5. Gain-to-feed
      efficiency (FCR) responded in a quadratic fashion, with maximum efficiency
      observed under the shortest daylength.   6. Mortality increased linearly with
      daylength for all time periods in both experiments.

PMID- 22404801
TI  - Ventilation rates in large commercial layer hen houses with two-year continuous
      monitoring.
AB  - 1. Ventilation controls the indoor environment and is critical for poultry
      production and welfare. Ventilation is also crucial for assessing aerial
      pollutant emissions from the poultry industry. Published ventilation data for
      commercial layer houses have been limited, and are mostly based on short-term
      studies, mainly because monitoring airflow from large numbers of fans is
      technically challenging.   2. A two-year continuous ventilation monitoring trial
      was conducted at two commercial manure belt houses (A and B), each with 250 000
      layers and 88 130-cm exhaust fans. All the fans were individually monitored with
      fan rotational speed sensors or vibration sensors. Differential static pressures
      across the house walls were also measured. Three fan performance assessment
      methods were applied periodically to determine fan degradations. Fan models were
      developed to calculate house ventilations.   3. A total of 693 and 678 complete
      data days, each containing >16 h of valid ventilation data, were obtained in
      houses A and B, respectively. The two-year mean ventilation rates of houses A and
      B were 2.08 and 2.10 m(3) h(-1) hen(-1), corresponding to static pressures of 
      36.5 and -48.9 Pa, respectively. For monthly mean ventilation, the maximum rates
      were 4.87 and 5.01 m(3) h(-1) hen(-1) in July 2008, and the minimum were 0.59 and
      0.81 m(3) h(-1) hen(-1) in February 2008, for houses A and B, respectively.   4.
      The two-year mean ventilation rates were similar to those from a survey in
      Germany and a 6-month study in Indiana, USA, but were much lower than the 8.4 and
      6.2 m(3) h(-1) hen(-1) from a study in Italy. The minimum monthly mean
      ventilation rates were similar to the data obtained in winter in Canada, but were
      lower than the minimum ventilation suggested in the literature. The lower static
      pressure in house B required more ventilation energy input. The two houses,
      although identical, demonstrated differences in indoor environment controls that
      represented potential to increase ventilation energy efficiency, and reduce
      carbon footprints and operational costs.

PMID- 22404802
TI  - Breeder age affects small intestine development of broiler chicks with immediate
      or delayed access to feed.
AB  - 1. The relationship between breeder age and chick gastrointestinal tract
      development to 21 days of age, as influenced by immediate or delayed access to
      feed, was examined in three consecutive trials.   2. Ross 708 chicks, derived
      from breeder flocks at 31 (young), 40 (middle) and 63 (old) weeks of age were
      placed randomly into either a control group with immediate access to feed and
      water, or a 48 h feed delayed (FD) group with free access to water.   3. FD
      negatively affected body weight (BW) of chicks derived from young and old flocks
      through the first and second weeks of age, respectively. Chicks from the older
      flock absorbed more yolk in the first 48 h with no FD effect. When feed was made
      available, chicks from the FD group showed a large increase in small intestine
      weight relative to BW, surpassing (P < 0.05) the control groups across all
      breeder flock ages.   4. Morphological measurements in all intestinal sections
      had higher values in chicks derived from the middle age breeder flock. FD to
      newly hatched chicks from the young breeder flock shortened villi (P < 0.01),
      decreased crypt depth and villus surface area (P < 0.001) in the duodenum through
      the first week post hatch.   5. Crypt depths were maximised between 7 and 14 d
      post-hatch in chicks from young and old breeder flocks, but crypt depths in
      chicks from the middle aged flocks continued to deepen.   6. The increased crypt
      depth may augment the number of enterocytes available for villus growth, and
      facilitate longer villi and greater villus surface area, in chicks from the
      middle age flocks. Intestinal morphological variation was associated with breeder
      flock age, which accounted for differential growth in chicks derived from young,
      middle, and old aged breeder flocks.

PMID- 22404803
TI  - IgY stability in eggs stored at room temperature or at +4 degrees C.
AB  - 1. The aim of this study was to investigate the stability of immunoglobulin-Y
      (IgY) in stored eggs from immunised hens.   2. Eggs from individual hens were
      randomised and stored for up to one month at room temperature, or for up to 6
      months at +4 degrees C. IgY was extracted from the egg yolks and the antibody
      activities were tested by ELISA.   3. There was no significant reduction in
      antibody titres with egg storage under these conditions.   4. Egg yolks of
      immunised chickens provide an inexpensive source of large amounts of polyclonal
      antibodies for use in immunotherapy and immunoassays. By collecting eggs from
      different immunised hens and pooling their yolks, it should be possible to reduce
      batch-to-batch variation.

PMID- 22404804
TI  - Gas composition in controlled atmosphere stunning affects turkey meat quality
      traits.
AB  - 1. Investigations were made into the breast and leg muscle energy metabolism, and
      the quality of breast meat of turkeys after controlled atmosphere stunning or
      stun-killing (CAS) with various gas mixtures. In addition, the effect on meat
      quality of an increase in the chilling rate of turkey breast meat after
      hypercapnic or anoxic stun-killing was studied.   2. A total of 35 turkey toms
      within two replicate pens were individually stunned during consecutive weeks
      using one of 4 CAS methods. The stunning gases tested were high CO(2)
      concentration (60% CO(2) in air), high N(2) concentration (98% N(2), < 2% O(2)),
      a mixture of 76% N(2) and 24% CO(2), and a biphasic method (first minute in
      mixture containing 40% CO(2), 30% N(2), and 30% O(2;) followed by two minutes in
      a mixture containing 60% CO(2) in air).   3. The birds stunned with N(2)
      displayed the highest initial reduction in muscle pH, but after 4 h post mortem
      there were no differences in pH values associated with the various CAS methods.  
      4. The CAS method alone had no statistically significant effect on the quality of
      turkey breast muscle when the chilling speed was rapid (0 degrees C for 4 h,
      followed by storage at 4 degrees C). When the chilling rate was slowed (20
      degrees C for 4 h followed by storage at 4 degrees C), a significant decrease in
      cooking loss and in Warner-Bratzler shear force was recorded for birds stun
      killed with CO(2).   5. This study shows that anoxic stun-killing with N(2) had
      no adverse effects on meat quality despite the rapid post mortem pH decrease. The
      CAS with N(2) allows rapid cooling of carcases without the risk of cold
      shortening, whereas with CO(2)-stun-killing of turkeys, the rate of chilling
      should be slower. Concerning meat quality, all the CAS methods tested were
      suitable for stunning turkeys.

PMID- 22404805
TI  - Colour, pH and weight changes of PSE, normal and DFD breast fillets from British
      broilers treated with a phosphate-free, low salt marinade.
AB  - 1. Colour (L*, a*, b*), pH and weight changes during tumbling, overnight holding
      and cooking were measured in pale, soft and exudative (PSE, L* > 58); normal; and
      dark, firm and dry (DFD, L* < 52) broiler breast fillets (n = 180) subject to
      tumbling in a low salt (4%), phosphate-free marinade at three target addition
      levels: 0, 10 and 20%.   2. The mean L* values for PSE, normal and DFD fillets
      were 60.1, 56.0 and 51.7 respectively, with corresponding mean pH values of 5.73,
      5.85 and 6.07.   3. There were no significant differences in marinade uptake
      during tumbling for the three groups of fillets. Losses during overnight holding
      were highest for the PSE fillets, but losses for all three colour groups were
      relatively small (<2%).   4. Cooking losses for fillets of normal colour were
      19.7, 24.1 and 26.2% at 0, 10 and 20% addition levels respectively, with
      corresponding yields of 80.3, 82.8 and 84.8%.   5. PSE fillets had higher cooking
      losses and lower yields than normal fillets (and DFD fillets had lower cooking
      losses and higher yields than normal fillets) but the differences were small and
      not always significant (P < 0.05).   6. There was a strong negative correlation
      between pH and L* (r = -0.82) in the raw fillets, but weaker correlations of
      yield with L* (r = -0.53) and pH (r = 0.38) in the cooked fillets.

PMID- 22404806
TI  - Melamine residues in eggs of quails fed on diets containing different levels of
      melamine.
AB  - 1. An experiment was conducted to determine residual melamine concentrations in
      eggs of quail given diets containing different concentrations of melamine, and to
      estimate the time at which withdrawing melamine from the diet would result in
      undetectable concentrations in eggs. A total of 600 Japanese quails (Coturnix
      coturnix japonica) were randomly divided into 5 treatments, and given melamine at
      concentrations of 0, 2, 10, 50, and 100 mg/kg diet respectively for 30 d. From d
      31 to 41, all quails were given a diet without melamine. Each diet was offered to
      4 replicates (cages) of 30 quails each. On d 11, 13, 15, 17, 19, 21, 23, 25, 27,
      29, 31, 33, 35, 37, 39, and 41, eggs were collected for the determination of
      melamine and cyanuric acid levels. 2. Throughout the 41 d experimental period,
      inclusion levels of melamine in the diets of quails had no significant effect on
      daily feed intake, egg production percentage, and feed efficiency. No detectable
      amount of cyanuric acid was found in all eggs. When the diets contained melamine
      at 2 mg/kg, the amounts of melamine in eggs were below the detection limit.
      During the entire 30 d exposure, the maximum melamine concentrations in eggs were
      0.162, 0.998 and 1.784 mg/kg for the 10, 50 and 100 mg/kg treatment groups,
      respectively, which demonstrated a linear dose-response relationship. 3. Upon
      feeding a diet without melamine, the melamine concentration in eggs decreased
      rapidly. The time taken for the amounts of melamine to decline below the
      detection limit were 1, 5, and 5 d for quails fed on the diets containing
      melamine at 10, 50, and 100 mg/kg respectively. 4. Melamine is not metabolised
      into cyanuric acid in quails, and a positive relationship exists between the
      concentrations in feed and in eggs.

PMID- 22404807
TI  - Isolation, identification and antimicrobial susceptibility of Bacteroides
      fragilis group strains recovered from broiler faeces.
AB  - 1. The objective was to evaluate the occurrence of cultivable components of the
      Bacteroides fragilis group in faeces of broiler chickens and their antimicrobial
      susceptibility patterns.   2. Faecal samples of 36 * 45-d-old Cobb broilers of
      both sexes from 15 different flocks on one farm were diluted 10-fold and plated
      on to Bacteroides-bile-esculin agar for colony count and isolation.
      Identification was by molecular methods and antimicrobial susceptibility in the
      agar dilution assay.   3. A total of 236 isolates was recovered from a mean
      population of 3.32 * 10(7 )colony-forming units/g of faeces. B. fragilis was
      shown to be the predominant Bacteroides species (45.3%), followed by B.
      distasonis (35.6%), B. vulgatus (8.9%), B. ovatus (2.5%) and B. stercoris (1.3%).
      4. Among 204 bacterial isolates tested, high resistance to ampicillin (98.5%),
      norfloxacin (95.1%) and tetracycline (88.2%) were observed. High (89.7%) multi
      drug resistance was observed to 3-7 of the tested drugs.   5. Components of the
      B. fragilis group were sub-dominant in broiler faecal microbiota, with a
      different species pattern compared with human and high antimicrobial multi-drug
      resistance.

PMID- 22404808
TI  - Effect of different dietary concentrations of inorganic and organic copper on
      growth performance and lipid metabolism of White Pekin male ducks.
AB  - 1. The effect of different dietary concentrations of inorganic and organic copper
      on performance and lipid metabolism of White Pekin ducks (WPD) was investigated
      from 1-49 d of age. A common basal diet was supplemented with 4, 8, 12 and 150
      mg/kg of copper (Cu) from inorganic and organic sources to obtain 9 treatments,
      including 4 concentrations of Cu x two sources, and the unsupplemented control
      group. Each treatment contained 5 replicates of 9 male ducks each.   2.
      Supplementation of Cu at 8 mg/kg in inorganic form was adequate for growth of
      male WPD from 1-56 d of age. Inorganic Cu significantly decreased feed intake and
      improved feed conversion ratio, compared with the organic form.   3. Plasma Cu
      significantly increased, while plasma Zn significantly decreased, due to Cu
      supplementation. Organic Cu showed better efficacy than inorganic for improving
      liver Cu concentration, Cu excretion and apparent Cu retention.   4. Dietary Cu
      concentration significantly affected percentage blood and Hgb and abdominal fat
      deposition. In addition, inorganic Cu increased percentage blood and abdominal
      fat deposition compared with the organic source.   5. Supplementation of 150
      mg/kg of Cu significantly decreased liver and meat lipids, cholesterol, and
      colour and tenderness of meat; while liver protein and moisture was increased. In
      addition, dietary 150 mg/kg of Cu supplementation significantly decreased plasma
      lipids, triglycerides and cholesterol, while increasing plasma AST and ALT.   6.
      Organic Cu was more potent for decreasing plasma triglycerides than the inorganic
      source. However, plasma cholesterol was only significantly decreased with the
      inorganic source of Cu, compared with the unsupplemented control.   7. The
      organic Cu was safer as a feed additive for WPD, especially at the lower
      concentrations up to 12 mg; while some mild to moderate changes may be developed
      at the higher doses, when fed at pharmacological concentrations as a growth
      promoter.

PMID- 22404809
TI  - Effect of a rosemary and oregano volatile oil mixture on performance, lipid
      oxidation of meat and haematological parameters in Pharaoh quails.
AB  - 1. This study was conducted to determine the utility of a volatile oil (VO)
      mixture in quail diets as a natural growth promoter. Different levels of VO
      mixtures, derived from rosemary and oregano, were added to a basal diet to
      determine the effects of the mixture on live weight (LW), live weight gain (LWG),
      feed intake, feed conversion ratio (FCR), carcase yield (CY), lipid oxidation
      level in thigh meat samples, and blood constituents.   2. A total of 880 one-day
      old Pharaoh (Coturnix coturnix Pharaoh) quails, including both males and females,
      were divided into 4 groups containing 220 quails and treated as follows: (1) a
      control treatment with 0 mg VO/kg of diet; (2) 100 mg/kg rosemary VO plus 100
      mg/kg oregano VO (50:50%); (3) 140 mg/kg oregano VO plus 60 mg/kg rosemary VO
      (70:30%); and (4) 60 mg/kg oregano VO plus 140 mg/kg rosemary VO (30:70%). The
      diets were prepared fresh for each treatment. The experiment was carried out for
      42 d.   3. The results of the study showed that the highest concentration of
      rosemary oil (140 mg/kg) caused a significant increase in live weight, live
      weight gain and carcase yields during the growing and finishing periods. However,
      feed intake and FCR were not significantly influenced by treatments.   4. The
      quails fed with rations containing the VO mixture derived from rosemary and
      oregano had reduced thiobarbituric acid levels (TBA) in raw breast meat samples
      at different storage times. There is possibly a synergistic effect between
      oregano and rosemary volatile oils in preventing lipid oxidation in stored meat. 
      5. In this study, the haemoglobin (PCV) and haematocrit values and the
      heterophile/lympohocyte (H/L) ratio increased in the blood samples taken from
      Treatment 2.   6. In conclusion, a volatile oil containing a mixture of rosemary
      and oregano oils could be a potential natural growth promoter for quails,
      depending on the plants from which the VOs were extracted, the dosage and the
      synergetic effects of the mixture.

PMID- 22404810
TI  - Effect of dietary nucleotide supplementation on performance and development of
      the gastrointestinal tract of broilers.
AB  - 1. Two experiments were conducted to determine the effects of dietary nucleotide
      supplementation on broiler performance, and physical and morphological
      development of the gastrointestinal tract.   2. Experiment 1: A total of 180 one
      d-old male chicks were placed in battery brooders in 3 * 6 replicate pens
      containing 10 chicks each. Chicks were randomly assigned to one of the three
      dietary treatments; a maize-soyabean meal based diet supplemented with 0, 0.25,
      and 0.50% Torula yeast RNA (as a source of nucleotides) from 0 to 16 d of age.  
      3. Experiment 2: A total of 1344 one-d-old male chicks were placed in floor pens
      and reared on recycled wood shavings (two flocks) under a high stocking density
      (0.068 m(2)/bird). Chicks were randomly assigned to one of the 4 dietary
      treatments (0, 0.25% Torula yeast RNA, 2% and 6% Nupro(r)) for the starter period
      (0 to 14 d of age) with 6 replicate pens containing 56 chicks each. All the birds
      were fed on the same common grower diet with no supplementation of nucleotides
      from 15 to 32 d of age.   4. Experiment 1: Supplementing the diets with up to
      0.50% Torula yeast RNA did not affect broiler performance, or relative intestinal
      tract weight and length of broilers at any periods measured.   5. Experiment 2:
      From 0 to 14 d of age, broilers fed on the diets supplemented with 0.25% Torula
      yeast RNA and 2 and 6% Nupro(r) were significantly heavier and had improved feed
      conversion (feed:gain) ratios as compared with the birds fed on the control diet.
      Supplementing the starter diet only with 2% Nupro(r) supplementation
      significantly improved body weight (BW) gain as compared with the control diet
      over the entire experiment (0 to 32 d of age). Broilers fed on the diets
      supplemented with 2 and 6% Nupro(r) from 0 to 14 d of age had better feed
      conversion (feed:gain) ratios over the entire experiment (0 to 32 d of age) as
      compared with the birds fed on the control diet, even though the birds were only
      fed on the diets supplemented with Nupro(r) from 0 to 14 d of age. The broilers
      fed on the diets supplemented with 0.25% Torula yeast RNA and 2% Nupro(r) had
      higher villus height and an improved villus height-to-crypt depth ratio as
      compared with birds fed on the control or 6% Nupro(r) diet at 14 d of age.   6.
      It is generally assumed that nucleotides are not an essential nutrient; thus
      there is no need to supplement the diets of broilers reared under normal
      conditions. However, dietary nucleotide supplementation may be important to
      maintain maximum growth performance when birds are exposed to stress conditions,
      such as high stocking density combined with dirty litter.

PMID- 22404811
TI  - Egg production, faecal pH and microbial population, small intestine morphology,
      and plasma and yolk cholesterol in laying hens given liquid metabolites produced
      by Lactobacillus plantarum strains.
AB  - 1. Various dosages of metabolite combinations of the Lactobacillus plantarum
      RI11, RG14 and RG11 strains (COM456) were used to study the egg production,
      faecal microflora population, faecal pH, small intestine morphology, and plasma
      and egg yolk cholesterol in laying hens.   2. A total of 500 Lohmann Brown hens
      were raised from 19 weeks to 31 weeks of age. The birds were randomly divided
      into 5 groups and fed on various treatment diets: (i) basal diet without
      supplementation of metabolites (control); (ii) basal diet supplemented with 0.3%
      COM456 metabolites; (iii) basal diet supplemented with 0.6% COM456 metabolites;
      (iv) basal diet supplemented with 0.9% COM456 metabolites; and (v) basal diet
      supplemented with 1.2% COM456 metabolites.   3. The inclusion of 0.6% liquid
      metabolite combinations, produced from three L. plantarum strains, demonstrated
      the best effect in improving the hens' egg production, faecal lactic acid
      bacteria population, and small intestine villus height, and reducing faecal pH
      and Enterobacteriaceae population, and plasma and yolk cholesterol
      concentrations.   4. The metabolites from locally isolated L. plantarum are a
      possible alternative feed additive in poultry production.

PMID- 22404812
TI  - Effect of dietary zinc proteinate supplementation on growth performance, and skin
      and meat quality of male and female broiler chicks.
AB  - 1. An experiment was conducted to evaluate the effect of dietary zinc proteinate
      (ZP) supplementation on growth performance and on skin and meat quality of male
      and female broiler chicks.   2. A total of 240 1-d-old male and 240 1-d-old
      female broiler chicks were randomly distributed into 24 floor pens (12 replicate
      pens/sex; 20 birds/pen) and were given either 0 (Control diet) or 40 mg/kg ZP (ZP
      40), resulting in a 2 * 2 factorial arrangement of treatments.   3. The growth
      performance of male and female broiler chicks was not affected by the ZP
      supplementation, but the males showed significantly higher growth performance
      than did females.   4. ZP supplementation increased the total thickness of skin
      in both sexes, and males had thicker skin than females. It also increased the
      collagen content of skin, but not that of meat. Males had higher skin collagen
      contents than did females, but no sex difference was found in the meat collagen
      contents.   5. ZP supplementation did not affect the shear force values of skin
      and meat; however, males had higher shear force values of back skin than females.
      ZP supplementation increased the zinc contents of thigh meat and plasma in both
      sexes. Males had higher zinc contents in back skin than females.   6. It is
      concluded that dietary ZP supplementation could increase the skin quality of
      broiler chicks in both sexes, particularly in female broilers, without any effect
      on growth performance. Male broilers have better growth performance and skin
      quality than females.

PMID- 22404813
TI  - Alleviative effects of alpha-lipoic acid supplementation on acute heat stress
      induced thermal panting and the level of plasma nonesterified fatty acids in
      hypothyroid broiler chickens.
AB  - 1. The present study was conducted to examine the effects of alpha-lipoic acid on
      hypothyroidism-induced negative growth performance and whether alpha-lipoic acid
      alleviates acute heat stress in relation to hypothyroid status.   2. Female
      broiler chickens (14 d-old) were fed diets supplemented with alpha-lipoic acid
      (100 mg/kg) and an antithyroid substance, propylthiouracil (200 mg/kg), for 20 d
      under thermoneutral conditions (25 degrees C). At 42 d of age, chickens were
      exposed to a high ambient temperature (36 degrees C, 60% RH) for 4 h.   3. Under
      the thermoneutral condition, propylthiouracil administration decreased feed
      efficiency and concomitantly increased adipose tissue and thyroid gland weights.
      Plasma nonesterified fatty acids and triacylglycerol were also increased by
      propylthiouracil administration. However, alpha-lipoic acid supplementation did
      not affect the hypothyroidism-induced effects.   4. In hypothyroid chickens, the
      rise in respiratory rate induced by heat exposure was greatly inhibited by alpha
      lipoic acid administration at 1 h, but this effect had disappeared at 4 h. In
      addition, a similar inhibitory effect on the concentrations of plasma
      nonesterified fatty acids was subsequently observed at 4 h.   5. Therefore, the
      present study suggested that alpha-lipoic acid alleviates acute heat stress if
      chickens are in a hypothyroid status.

PMID- 22404814
TI  - The ostrich (Struthio camelus) ejaculate--effects of the method of collection,
      male age, month of the season, and daily frequency.
AB  - 1. Over three breeding seasons on a farm in Poland, semen was collected from 11
      ostriches using the dummy and the teaser method to study the effects of the
      method of collection, male age, month in the breeding season, and daily
      collection frequency on ejaculate characteristics.   2. A total of 259 ejaculates
      were collected, with an average volume of 1.28 +/- 0.6 (+/-SEM) ml. Sperm
      concentration was 3.34 +/- 0.08 * 10(9)/ml, the total number of spermatozoa 4.32
      +/- 0.22 * 10(9), and motility 4.56 +/- 0.04.   3. There was no difference in
      ejaculates collected by the dummy and teaser methods, but the between-individual
      variation was considerable. Ejaculate characteristics increased with male age and
      varied between months, with little evidence for seasonal decline. Daily
      collections for 10 days did not affect sperm output.   4. The results open up
      avenues for further research on development of a viable protocol for artificial
      insemination in ostriches and efficient semen storage.   5. The between-male
      variation suggests that the ejaculate output could be maximized through
      selection.

PMID- 22404815
TI  - Growth and development of chicks of two species of partridge: the grey partridge
      (Perdix perdix) and the chukar (Alectoris chukar).
AB  - 1. In two partridge species, the grey partridge (Perdix perdix) and chukar
      (Alectoris chukar), from hatching up to 120 d, the growth rate and development of
      body mass, wing, tarsus, and bill length were measured and fitted by Gompertz
      equations.   2. As a typical precocial species, partridges hatched with
      relatively well developed legs and bills, and wing growth followed a gradual
      development of thermoregulation.   3. Gompertz growth constants for body mass
      growth were 0.039 and 0.038 for grey partridges and chukars, respectively.   4.
      The allometric relationship between tarsus length and body mass followed a
      geometric similarity (1/3 power) in both grey partridges and chukars.

PMID- 22404816
TI  - Changes in brain monoamine metabolism of neonatal chicks under two different
      acute stress conditions.
AB  - 1. The purpose of the present study was to clarify brain monoamine metabolism
      during two different conditions of acute stress by quantifying changes in the
      brain of neonatal chicks exposed to either restraint with isolation, or fasting
      stress.   2. Under restraint with isolation-induced stress, dopaminergic
      metabolism was clearly stimulated.   3. During fasting stress, dopaminergic
      activity, serotonergic and norepinephrinergic metabolisms were stimulated.   4.
      It was concluded that brain monoamine metabolism of chicks is differentially
      affected by stressors.

PMID- 22404817
TI  - Obituary--Dr Walter George Siller.

PMID- 22404818
TI  - Residues of currently and never used organochlorine pesticides in agricultural
      soils from Zhejiang Province, China.
AB  - Studies on residues of currently and never used organochlorine pesticides (OCPs)
      facilitate the assessment of the contamination level, distribution, sources,
      transportation, and trend of these selected OCPs in China. In this work we
      investigated the concentration levels of endosulfans and chlordane, which are
      currently used, and the never used aldrin and dieldrin in the province of
      Zhejiang, a rainy, and hilly tea-growing province in eastern China. The
      average/mean residue levels of OCPs was in the order ?endosulfan > ?chlordane >
      aldrin > dieldrin. The residue level was in good agreement with the usage of OCPs
      in Zhejiang. The spatial distribution showed that the residues of OCPs in soils
      from the mountain area were always higher than those in soils from the plains.
      The distribution characteristics were related to usage for current-use OCPs and
      temperature for never used OCPs. The isomeric ratios and enantiomeric fractions
      are useful tools to identify the degradation preference of contaminants. The wide
      range of ratios between trans-chlordane (TC) and cis-chlordane (CC) indicated
      that the degradation of the two isomers of chlordane was different at different
      sites. Nonracemic residues of TC and CC were observed in most soils; this is
      significant since the enantiomers have different toxicities.

PMID- 22404819
TI  - Ultrastructural changes of sparkling wine lees during long-term aging in real
      enological conditions.
AB  - Ultrastructural changes of lees of three series of sparkling wines produced using
      the traditional method during long-term aging (4 years) were assessed by high
      pressure freezing in combination with transmission electron microscopy. The
      stratified structure of the cell wall disappeared throughout aging. After 18
      months, the microfibrous material of the cell wall appeared more diffuse and the
      amorphous midzone of the inner wall layer was progressively degraded. From 30
      months onward, the cell wall consisted of a tangled structure of fibers. In spite
      of these changes, the cell wall of yeasts remained unbroken at 48 months of wine
      aging. Cell membrane breakage was observed for the first time in lees of
      Saccharomyces cerevisiae. An increase in the thickness of the periplasmic space
      owing to plasmolysis and of the number of cells with less cytoplasmic content was
      observed during aging. Morphological evidence of microautophagy was detected for
      the first time in S. cerevisiae in enological conditions.

PMID- 22404820
TI  - Retina ganglion cell degeneration in glaucoma: an opportunity missed? A review.
AB  - Retinal ganglion cell degeneration has been reported in a range of experimental
      models of glaucoma. Manifest as pruning of retinal ganglion cell dendrites, it is
      likely to influence both the function and viability of affected cells.
      Electrophysiological studies in primate glaucoma have shown that affected cells
      retain some function and could therefore form a neural substrate for the recovery
      of visual function in glaucoma. Clinical studies in which the intraocular
      pressure is reduced have suggested that some improvement in retinal function may
      be possible in hypotensive eyes. These experimental studies highlight the
      importance of establishing the extent to which retinal ganglion cell degeneration
      occurs in human glaucoma. If substantial numbers of degenerating retinal ganglion
      cells are present in glaucoma, they could present an ideal target for the
      recovery of vision.

PMID- 22404821
TI  - Classification of binding site conformations of protein tyrosine phosphatase 1B.
AB  - Hundred and two binding sites from 91 Protein Data Bank files for protein
      tyrosine phosphatase 1B with different ligands have been compared. It was found
      that they can be divided into five clusters. Additional clusters were formed by
      the unliganded and oxidized enzyme. The centroids of the clusters can be used as
      starting points for further studies of enzyme-inhibitor interaction by computer
      simulations. A special software tool has been created for the investigation of
      protein tyrosine phosphatase 1B and other enzymes. It performs multiple
      comparisons of selected parts of Protein Data Bank files, as well as further
      clustering, and determines mobility of separate residues.

PMID- 22404822
TI  - Evaluation of the tolerability and immunogenicity of ultraviolet C-irradiated
      autologous platelets in a dog model.
AB  - BACKGROUND: The THERAFLEX ultraviolet (UV) platelets (PLTs) pathogen reduction
      system for PLT concentrates (PCs) operates using ultraviolet C (UVC) light at a
      wavelength of 254 nm. UVC treatment can potentially alter proteins, which may
      affect drug tolerance in humans and influence the immunogenicity of blood
      products. This preclinical study in beagle dogs was designed to evaluate the
      safety pharmacology of UVC-irradiated PCs after intravenous administration and to
      determine whether they are capable of eliciting humoral responses to PLTs and
      plasma proteins. STUDY DESIGN AND METHODS: Six beagle dogs each were transfused
      once every other week for 10 weeks with UVC-irradiated or nonirradiated PCs. All
      PCs were autologous canine single-donor products prepared from whole blood.
      Safety pharmacology variables were regularly assessed. The impact of UVC
      irradiation on PLT and plasma proteomes was analyzed by one- and two-dimensional
      gel electrophoresis. Serum samples were tested for UVC-induced antibodies by
      Western blot and flow cytometry. RESULTS: Dogs transfused with UVC-irradiated PCs
      showed no signs of local or systemic intolerance. Few but significant changes in
      PLT protein integrity were observed after UVC irradiation. Even after repeated
      administration of UVC-irradiated PCs, no antibodies against UVC-exposed plasma or
      PLT proteins were detected. CONCLUSIONS: Repeated transfusions of autologous UVC
      treated PCs were well tolerated in all dogs studied. UVC irradiation did not
      cause significant plasma or PLT protein modifications capable of inducing
      specific antibody responses in the dogs. High-resolution proteomics combined with
      antibody analysis introduces a comprehensive and sensitive method for screening
      of protein modifications and antibodies specific for pathogen reduction
      treatment.

PMID- 22404823
TI  - Significance of the conformation of building blocks in curing of barnacle
      underwater adhesive.
AB  - Barnacles are a unique sessile crustacean that attach irreversibly and firmly to
      foreign underwater surfaces. Its biological underwater adhesive is a peculiar
      extracellular multi-protein complex. Here we characterize one of the two major
      proteins, a 52 kDa protein found in the barnacle cement complex. Cloning of the
      cDNA revealed that the protein has no homolog in the nonredundant database. The
      primary structure consists of four long sequence repeats. The process of
      dissolving the protein at the adhesive joint of the animal by various treatments
      was monitored in order to obtain insight into the molecular mechanism involved in
      curing of the adhesive bulk. Treatments with protein denaturant, reducing agents
      and/or chemical-specific proteolysis in combination with 2D diagonal PAGE
      indicated no involvement of the protein in intermolecular cross
      linkage/polymerization, including formation of intermolecular disulfide bonds. As
      solubilization of the proteins required high concentrations of denaturing agents,
      it appears that both the conformation of the protein as building blocks and non
      covalent molecular interactions between the building blocks, possibly hydrophobic
      interactions and hydrogen bonds, are crucial for curing of the cement. It was
      also suggested that the protein contributes to surface coupling by an anchoring
      effect to micro- to nanoscopic roughness of surfaces.

PMID- 22404824
TI  - Unclassified renal cell carcinoma: a report of 56 cases.
AB  - What's known on the subject? and What does the study add? Unclassified RCC
      represents 0.7-5.7% of renal tumours. Limited reported data from two series
      suggests that unclassified RCC is an aggressive form of RCC, mainly because most
      cases are at an advanced stage at presentation, but overall and cancer-specific
      survival were not significantly different between unclassified and clear-cell RCC
      in an additional series of 38 patients. Our study of 56 cases of unclassified RCC
      describes the pathological features that can be applied to predict prognosis on a
      daily basis. In particular nuclear grade, TNM classification, tumour coagulative
      necrosis, tumour size, microvascular invasion and 2004 WHO histotype are
      independent predictors of disease-free and cancer-specific survival. OBJECTIVE:
      To evaluate the clinicopathological features and outcomes of 56 patients with
      unclassified renal cell carcinoma (RCC) meeting 2004 World Health Organization
      diagnostic criteria. PATIENTS AND METHODS: Urological pathology files of the
      participating institutions were reviewed and cases of unclassified RCC that met
      the inclusion criteria were retrieved. Nuclear grade, pT status, tumour size,
      regional lymph node involvement, distant metastases, coagulative tumour necrosis,
      mucin and sarcomatoid differentiation were evaluated in radical nephrectomy or
      nephron-sparing specimens. Significant factors in univariate analysis were then
      assessed by a multivariate analysis of independent prognostic factors using Cox
      proportional hazard regression analysis. RESULTS: Fifty-six cases met the
      histological criteria for unclassified RCC. Thirty-four (61%) cases were
      categorized as unrecognizable cell type (mean overall survival 47 months; median
      36 months), 20 (36%) as composites of recognized types (mean overall survival 36
      months; median 26 months), and two (4%) (mean survival 16 months; median 16
      months) as pure sarcomatoid morphology without recognizable epithelial elements.
      Cox multivariate analysis showed nuclear grade (P = 0.020), stage (P < 0.001),
      tumour coagulative necrosis (P = 0.018), tumour size (P < 0.001), microvascular
      invasion (P < 0.001) and tumour histotype (P = 0.028) to be independent
      predictors of disease-free survival, with tumour size being the most significant
      (hazard ratio [HR] 9.068, 95% confidence interval [CI] 3.231-25.453). Nuclear
      grade (P = 0.026), stage (P < 0.001), tumour coagulative necrosis (P < 0.001),
      tumour size (P = 0.044), microvascular invasion (P < 0.001), tumour recurrence
      after surgery (P < 0.001) and tumour histotype (P = 0.056) were independent
      predictors of cancer-specific survival, with tumour recurrence after surgery
      being the most significant (HR 14.713, 95% CI 5.329-40.622). CONCLUSION: The
      prognosis of patients with unclassified RCC seems to be related to
      clinicopathological features known to be relevant in common forms of RCC.

PMID- 22404825
TI  - Experience of recovery from a first-episode psychosis.
AB  - AIM: To understand the subjective factors involved in the recovery process
      following a first-episode psychosis. METHOD: Sixteen individuals from a First
      Episode Program in Sao Paulo, Brazil were evaluated by a semistructured interview
      designed to elicit an in-depth narrative of participants' subjective experience
      of recovery after a first-episode psychosis. Eligibility was established by using
      the Structured Clinical Interview for DSM-IV Axis I Disorders. The interviews
      were recorded, the transcripts were coded and themes were grouped together to
      form conceptual categories. RESULTS: The participants described the recovery
      course as a slow and gradual process. Improvement was perceived as based on a
      decrease or absence of psychotic symptoms, changes in social relationships,
      renewed autonomy and independence, and restoration of self-reliance and trust in
      others. CONCLUSIONS: Recovering after a first-episode psychosis can be considered
      a complex process correlated with treatment, social support, and individual
      experiences and characteristics. These are important areas to be addressed in
      first psychotic psychosis interventions, and gains can probably only be obtained
      in specialized first-episode psychosis programmes.

PMID- 22404827
TI  - The microtubule associated protein END BINDING 1 represses root responses to
      mechanical cues.
AB  - The ability of roots to navigate around rocks and other debris as they grow
      through the soil requires a mechanism for detecting and responding to input from
      both touch and gravity sensing systems. The microtubule associated protein END
      BINDING 1b (EB1b) is involved in this process as mutants have defects responding
      to combinations of touch and gravity cues. This study investigates the role of
      EB1b in root responses to mechanical cues. We find that eb1b-1 mutant roots
      exhibit an increase over wild type in their response to touch and that the
      expression of EB1b genes in transgenic mutants restores the response to wild type
      levels, indicating that EB1b is an inhibitor of the response. Mutant roots are
      also hypersensitive to increased levels of mechanical stimulation, revealing the
      presence of another process that activates the response. These findings are
      supported by analyses of double mutants between eb1b-1 and seedlings carrying
      mutations in PHOSPHOGLUCOMUTASE (PGM), ALTERED RESPONSE TO GRAVITY1 (ARG1), or
      TOUCH3 (TCH3), genes that encode proteins involved in gravity sensing, signaling,
      or touch responses, respectively. A model is proposed in which root responses to
      mechanical cues are modulated by at least two competing regulatory processes, one
      that promotes touch-mediated growth and another, regulated by EB1b, which dampens
      root responses to touch and enhances gravitropism.

PMID- 22404826
TI  - Possible genetic predisposition to lymphedema after breast cancer.
AB  - BACKGROUND: Known risk factors for secondary lymphedema only partially explain
      who develops lymphedema following cancer, suggesting that inherited genetic
      susceptibility may influence risk. Moreover, identification of molecular
      signatures could facilitate lymphedema risk prediction prior to surgery or lead
      to effective drug therapies for prevention or treatment. Recent advances in the
      molecular biology underlying development of the lymphatic system and related
      congenital disorders implicate a number of potential candidate genes to explore
      in relation to secondary lymphedema. METHODS AND RESULTS: We undertook a nested
      case-control study, with participants who had developed lymphedema after surgical
      intervention within the first 18 months of their breast cancer diagnosis serving
      as cases (n=22) and those without lymphedema serving as controls (n=98),
      identified from a prospective, population-based, cohort study in Queensland,
      Australia. TagSNPs that covered all known genetic variation in the genes SOX18,
      VEGFC, VEGFD, VEGFR2, VEGFR3, RORC, FOXC2, LYVE1, ADM, and PROX1 were selected
      for genotyping. Multiple SNPs within three receptor genes, VEGFR2, VEGFR3, and
      RORC, were associated with lymphedema defined by statistical significance
      (p<0.05) or extreme risk estimates (OR <0.5 or >2.0). CONCLUSIONS: These
      provocative, albeit preliminary, findings regarding possible genetic
      predisposition to secondary lymphedema following breast cancer treatment warrant
      further attention for potential replication using larger datasets.

PMID- 22404828
TI  - Control of the actin cytoskeleton in root hair development.
AB  - The development of root hair includes four stages: bulge site selection, bulge
      formation, tip growth, and maturation. The actin cytoskeleton is involved in all
      of these stages and is organized into distinct arrangements in the different
      stages. In addition to the actin configuration, actin isoforms also play distinct
      roles in the different stages. The actin cytoskeleton is regulated by actin
      binding proteins, such as formin, Arp2/3 complex, profilin, actin depolymerizing
      factor, and villin. Some upstream signals, i.e. calcium, phospholipids, and small
      GTPase regulate the activity of these actin-binding proteins to produce the
      proper actin configuration. We constructed a working model on how the actin
      cytoskeleton is controlled by actin-binding proteins and upstream signaling in
      root hair development based on the current literature: at the tip of hairs, actin
      polymerization appears to be facilitated by Arp2/3 complex that is activated by
      small GTPase, and profilin that is regulated by phosphatidylinositol 4,5
      bisphosphate. Meanwhile, actin depolymerization and turnover are likely mediated
      by villin and actin depolymerizing factor, which are stimulated by calcium. At
      the shank, actin cables are produced by formin and villin. Under the complicated
      interaction, the actin cytoskeleton is controlled spatially and temporally during
      root hair development.

PMID- 22404829
TI  - Evaluating the potential of SHI expression as a compacting tool for ornamental
      plants.
AB  - Control of plant growth, especially elongation of stems, is important in modern
      plant production, and many plant species, including cereals, grasses, fruit trees
      and ornamentals, are regularly treated chemically to control their stature and
      flowering time. Chemical treatments ensure short, homogenous plants, which are
      more robust and easy to harvest, transport and sell. Although growth retardants
      are an expensive and undesirable step in plant production, it is unfortunately
      necessary at present. Compact growth is desirable in most ornamentals and this
      trait can be difficult to obtain by traditional breeding. As an alternative,
      biotechnology could provide plant varieties with optimized growth habits. This
      review is an introduction to the family of SHI transcription factors, which has
      recently been used to produce compact plants of very diverse species. The
      possible functions and regulations of the SHI proteins are discussed, and the
      potential of using overexpression as means to dwarf plants is assessed. In
      conclusion the breeding of some species, especially flowering ornamentals, could
      benefit from this strategy. Furthermore, detailed knowledge about the role of SHI
      proteins in plant growth and development could help shed more light on the
      interactions between plant hormone signaling pathways.

PMID- 22404830
TI  - Ethylene produced by the endosperm is involved in the regulation of nucellus
      programmed cell death in Sechium edule Sw.
AB  - The nucellus is a maternal tissue that feeds the developing embryo and the
      secondary endosperm. During seed development the cells of the nucellus suffer a
      degenerative process early after fertilization as the cellular endosperm expands
      and accumulates reserves. Nucellar cell degeneration has been characterized as a
      form of developmentally programmed cell death (PCD). In this work we analysed the
      role of the endosperm as main regulator of nucellus PCD. We demonstrated that
      endosperm produces high amount of ethylene, nitric oxide and indoleacetic acid.
      We examined the role of these small and diffusible signalling molecules in the
      regulation of nucellus PCD and we tried to elucidate how they can cooperate and
      regulate each other into the endosperm. We showed that ethylene acts a positive
      regulator of nucellus PCD and its synthesis can be in part induced by nitric
      oxide. High levels of IAA were detected both in the endosperm and in dying
      nucellus but this hormone is not directly involved in the execution of PCD.

PMID- 22404831
TI  - Changes in expression of soluble inorganic pyrophosphatases of Phaseolus vulgaris
      under phosphate starvation.
AB  - Phosphorus is an essential element for all living cells, but its availability is
      often limiting in the soil. Plants have adapted to such limitation and respond to
      phosphorus deficiency. The soluble inorganic pyrophosphatases (PPase; EC 3.6.1.1)
      recycle the pyrophosphate produced by many biosynthetic reactions, and may play a
      role in the plant adaptation to phosphorus deficiency. In this work, three PPase
      mRNAs were identified from the Phaseolus vulgaris EST international database and
      their sequences were corroborated and completed using 3'RACE. After design and
      validation of the appropriate oligonucleotide primers, the PPase mRNA expression
      was measured by qRT-PCR in leaves, stems, and roots of bean plants grown with 1mM
      phosphate or under phosphate starvation. The plant tissues were classified
      according to their position on the plant, and some physiological signs of stress
      were recorded. qRT-PCR revealed changes in mRNA expression, but not for all
      isozymes under analysis, and not for all tissues. In addition, changes in the
      activity of some PPases were observed in zymograms. Our data are consistent with
      an important role for pyrophosphate in the adaptation of the plant to phosphate
      starvation.

PMID- 22404832
TI  - Small high-yielding binary Ti vectors pLSU with co-directional replicons for
      Agrobacterium tumefaciens-mediated transformation of higher plants.
AB  - Small high-yielding binary Ti vectors of Agrobacterium tumefaciens were
      constructed to increase the cloning efficiency and plasmid yield in Escherichia
      coli and A. tumefaciens for transformation of higher plants. We reduced the size
      of the binary vector backbone to 4566bp with ColE1 replicon (715bp) for E. coli
      and VS1 replicon (2654bp) for A. tumefaciens, a bacterial kanamycin resistance
      gene (999bp), and the T-DNA region (152bp). The binary Ti vectors with the
      truncated VS1 replicon were stably maintained with more than 98% efficiency in A.
      tumefaciens without antibiotic selection for 4 days of successive transfers. The
      transcriptional direction of VS1 replicon can be the same as that of ColE1
      replicon (co-directional transcription), or opposite (head-on transcription) as
      in the case of widely used vectors (pPZP or pCambia). New binary vectors with co
      directional transcription yielded in E. coli up to four-fold higher
      transformation frequency than those with the head-on transcription. In A.
      tumefaciens the effect of co-directional transcription is still positive in up to
      1.8-fold higher transformation frequency than that of head-on transcription.
      Transformation frequencies of new vectors are over six-fold higher than those of
      pCambia vector in A. tumefaciens. DNA yields of new vectors were three to five
      fold greater than pCambia in E. coli. The proper functions of the new T-DNA
      borders and new plant selection marker genes were confirmed after A. tumefaciens
      mediated transformation of tobacco leaf discs, resulting in virtually all treated
      leaf discs transformed and induced calli. Genetic analysis of kanamycin
      resistance trait among the progeny showed that the kanamycin resistance and
      sensitivity traits were segregated into the 3:1 ratio, indicating that the
      kanamycin resistance genes were integrated stably into a locus or closely linked
      loci of the nuclear chromosomal DNA of the primary transgenic tobacco plants and
      inherited to the second generation.

PMID- 22404833
TI  - Identification of sucrose-responsive microRNAs reveals sucrose-regulated copper
      accumulations in an SPL7-dependent and independent manner in Arabidopsis
      thaliana.
AB  - Sucrose induces the expression of miR398 and the production of miR398 is
      controlled by SQUAMOSA promoter binding protein-like7 (SPL7) transcription factor
      under copper deficiency in Arabidopsis thaliana. Little else, however, is known
      about the sucrose-regulated copper homeostasis in Arabidopsis. Here, we employed
      the microarray technology to screen for sucrose-responsive microRNAs (miRNAs),
      and identified several candidates using northern blotting. In addition to miR398,
      miR408, miR319, and miR160 are also responsive to sucrose. Furthermore, the
      induction of miR398 and miR408 by sucrose depends on the presence of SPL7. MiR398
      and miR408 induction by high sucrose was eliminated by high copper. Meanwhile,
      high sucrose treatment strongly suppressed copper accumulation. Knock-down of
      SPL7 dramatically reduced copper accumulation in plants under low sucrose, but
      this effect was compromised in the presence of high levels of sucrose. Taken
      together, these results suggest a connection between sucrose signaling and copper
      accumulation in cells, and that sucrose-regulated copper accumulation is both
      SPL7-dependent and SPL7-independent in Arabidopsis.

PMID- 22404834
TI  - Insights into salicylic acid responses in cucumber (Cucumis sativus L.)
      cotyledons based on a comparative proteomic analysis.
AB  - To investigate the response of cucumber seedlings to exogenous salicylic acid
      (SA) and gain a better understanding of SA action mechanism, we generated a
      proteomic profile of cucumber (Cucumis sativus L.) cotyledons treated with
      exogenous SA. Analysis of 1500 protein spots from each gel revealed 63
      differentially expressed proteins, 59 of which were identified successfully. Of
      the identified proteins, 97% matched cucumber proteins using a whole cucumber
      protein database based on the newly completed genome established by our
      laboratory. The identified proteins were involved in various cellular responses
      and metabolic processes, including antioxidative reactions, cell defense,
      photosynthesis, carbohydrate metabolism, respiration and energy homeostasis,
      protein folding and biosynthesis. The two largest functional categories included
      proteins involved in antioxidative reactions (23.7%) and photosynthesis (18.6%).
      Furthermore, the SA-responsive protein interaction network revealed 13 key
      proteins, suggesting that the expression changes of these proteins could be
      critical for SA-induced resistance. An analysis of these changes suggested that
      SA-induced resistance and seedling growth might be regulated in part through
      pathways involving antioxidative reactions and photosynthesis.

PMID- 22404835
TI  - Functional roles of the protein phosphatase 2C, AtAIP1, in abscisic acid
      signaling and sugar tolerance in Arabidopsis.
AB  - Biotic signaling molecules including abscisic acid (ABA) serve as an integrator
      of abiotic stress including high salinity and drought. Recent studies have led to
      the identification of an ABA signaling pathway from the ABA receptor to stomatal
      closure in response to abiotic stress. ABA is linked to ABA receptors and protein
      phosphatase 2C (PP2C) members. In this study, we reconstituted the ABA signaling
      pathway as a protein-protein interaction between the RCAR type receptor and AIP1,
      which is one of the group A PP2C member. Several ABA receptors interact with AIP1
      in an ABA dependent or independent manner. aip1 null mutant plants exhibited
      reduced sensitivity to ABA and glucose during the seed germination and seedling
      stage. Taken together, these results demonstrated that AIP1 is associated with
      ABA-mediated cell signaling and function as positive regulators of ABA.

PMID- 22404836
TI  - Characterization of the ABA signal transduction pathway in Vitis vinifera.
AB  - The plant hormone abscisic acid (ABA) regulates many key processes in plants
      including the response to abiotic stress. ABA signal transduction consists of a
      double-negative regulatory mechanism, whereby ABA-bound PYR/RCARs inhibit PP2C
      activity, and PP2Cs inactivate SnRK2s. We studied and analyzed the various genes
      participating in the ABA signaling cascade of the grape (Vitis vinifera). The
      grape ABA signal transduction consists of at least six SnRK2s. Yeast two-hybrid
      system was used to test direct interactions between core components of grape ABA
      signal transduction. We found that a total of forty eight interactions can occur
      between the various components. Exogenous abscisic acid (ABA) and abiotic
      stresses such as drought, high salt concentration and cold, were applied to vines
      growing in a hydroponic system. These stresses regulated the expression of
      various grape SnRK2s as well as ABFs in leaves and roots. Based on the
      interactions between SnRK2s and its targets and the expression pattern, we
      suggest that VvSnRK2.1 and VvSnRK2.6, can be considered the major VvSnRK2
      candidates involved in the stomata response to abiotic stress. Furthermore, we
      found that the expression pattern of the two grape ABF genes indicates organ
      specificity of these genes. The key role of ABA signaling in response to abiotic
      stresses makes the genes involve in this signaling potential candidates for
      manipulation in programs designed to improve fruit tree performance in extreme
      environments.

PMID- 22404837
TI  - A basal carbon concentrating mechanism in plants?
AB  - Many photosynthetic organisms have developed inorganic carbon (Ci) concentrating
      mechanisms (CCMs) that increase the CO2 concentration within the vicinity of
      ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO). Several CCMs, such as
      four carbon (C4) and crassulacean acid metabolism (CAM), bicarbonate accumulation
      systems and capsular structures around RubisCO have been described in great
      detail. These systems are believed to have evolved several times as mechanisms
      that acclimate organisms to unfavourable growth conditions. Based on recent
      experimental evidence we propose the occurrence of another more general CCM
      system present in all plants. This basal CCM (bCCM) is supposed to be composed of
      mitochondrial carbonic anhydrases (a beta-type carbonic anhydrase and the gamma
      type carbonic anhydrase domain of the mitochondrial NADH dehydrogenase complex)
      and probably further unknown components. The bCCM is proposed to reduce leakage
      of CO2 from plant cells and allow efficient recycling of mitochondrial CO2 for
      carbon fixation in chloroplasts.

PMID- 22404838
TI  - Cytokinins in shoot apices of Brassica napus plants during vernalization.
AB  - The putative role of cytokinins in processes leading to reproductive development
      of plants was investigated by analysing the shoot apical parts of a winter
      cultivar of oilseed rape (Brassica napus L. var. oleifera, cv. Gorczanski). The
      endogenous cytokinin levels were measured by liquid chromatography-tandem mass
      spectrometry (LC-MS) in the shoot apices of vegetative plants (grown at 20/17
      degrees C with a 16/8h day/night regime) and vernalized plants (56 days at 5/2
      degrees C with a 16/8h photoperiod) at different times during floral transition.
      During vernalization, the content of all isoprenoid cytokinins increased
      significantly, coinciding well with the onset of the early stages of reproductive
      development. Cytokinin levels reached their maxima when most of the plants became
      irreversibly reproductive (after 42 days of cold treatment). cis-Zeatin riboside
      (unequivocally identified by quadrupole-time-of-flight MS) accounted for ca. 87
      89% of the total isoprenoid cytokinin content in control and vernalized plants,
      whilst N(6)-isopentenyladenosine ( approximately 6% in control and approximately
      8% in vernalized plants) and cis-zeatin (approxiamtely 2% in control and
      approximately 1% in vernalized plants) were the next most abundant cytokinins. In
      the post-vernalization period, endogenous cytokinin levels decreased, but
      remained significantly higher in the reproductive plants than in the vegetative
      controls. These results suggest that cytokinins, especially those of the cis
      zeatin type, are involved in vernalization-induced reproductive development of B.
      napus.

PMID- 22404839
TI  - Chromium-induced physiological and proteomic alterations in roots of Miscanthus
      sinensis.
AB  - Despite the widespread occurrence of chromium toxicity, its molecular mechanism
      is poorly documented in plants compared to other heavy metals. To investigate the
      molecular mechanisms that regulate the response of Miscanthus sinensis roots to
      elevated level of chromium, seedlings were grown for 4 weeks and exposed to
      potassium dichromate for 3 days. Physiological, biochemical and proteomic changes
      in roots were investigated. Lipid peroxidation and H2O2 content in roots were
      significantly increased. Protein profiles analyzed by two-dimensional gel
      electrophoresis revealed that 36 protein spots were differentially expressed in
      chromium-treated root samples. Of these, 13 protein spots were up-regulated, 21
      protein spots were down-regulated and 2 spots were newly induced. These
      differentially displayed proteins were identified by MALDI-TOF and MALDI-TOF/TOF
      mass spectrometry. The identified proteins included known heavy metal-inducible
      proteins such as carbohydrate and nitrogen metabolism, molecular chaperone
      proteins and novel proteins such as inositol monophosphatase, nitrate reductase,
      adenine phosphoribosyl transferase, formate dehydrogenase and a putative
      dihydrolipoamide dehydrogenase that were not known previously as chromium
      responsive. Taken together, these results suggest that Cr toxicity is linked to
      heavy metal tolerance and senescence pathways, and associated with altered
      vacuole sequestration, nitrogen metabolism and lipid peroxidation in Miscanthus
      roots.

PMID- 22404840
TI  - An altered redox balance mediates the hypersensitivity of Cockayne syndrome
      primary fibroblasts to oxidative stress.
AB  - Cockayne syndrome (CS) is a rare hereditary multisystem disease characterized by
      neurological and development impairment, and premature aging. Cockayne syndrome
      cells are hypersensitive to oxidative stress, but the molecular mechanisms
      involved remain unresolved. Here we provide the first evidence that primary
      fibroblasts derived from patients with CS-A and CS-B present an altered redox
      balance with increased steady-state levels of intracellular reactive oxygen
      species (ROS) and basal and induced DNA oxidative damage, loss of the
      mitochondrial membrane potential, and a significant decrease in the rate of basal
      oxidative phosphorylation. The Na/K-ATPase, a relevant target of oxidative
      stress, is also affected with reduced transcription in CS fibroblasts and normal
      protein levels restored upon complementation with wild-type genes. High
      resolution magnetic resonance spectroscopy revealed a significantly perturbed
      metabolic profile in CS-A and CS-B primary fibroblasts compared with normal cells
      in agreement with increased oxidative stress and alterations in cell
      bioenergetics. The affected processes include oxidative metabolism, glycolysis,
      choline phospholipid metabolism, and osmoregulation. The alterations in
      intracellular ROS content, oxidative DNA damage, and metabolic profile were
      partially rescued by the addition of an antioxidant in the culture medium
      suggesting that the continuous oxidative stress that characterizes CS cells plays
      a causative role in the underlying pathophysiology. The changes of oxidative and
      energy metabolism offer a clue for the clinical features of patients with CS and
      provide novel tools valuable for both diagnosis and therapy.

PMID- 22404841
TI  - Apoptosis in seborrheic keratoses: an open door to a new dermoscopic score.
AB  - The aetiology of seborrheic keratoses (SK), the most common benign epithelial
      tumours, and any relationship with malignancy are not yet known. As a protective
      anti-cancer mechanism, apoptosis reflects cellular loss as a reaction to
      proliferative activity. The objective of this study was to quantify apoptosis in
      different SK types (acanthotic, hyperkeratotic, reticulated, irritated and
      clonal) and correlate the dermoscopic picture with apoptosis rate. After a
      qualitative and quantitative analysis of dermoscopic images, we defined a new
      quantitative dermoscopic score (C3V2F, crypts, millia cysts, colours, hairpin
      vessels, irregular vessels, fissures) from 0 to 22, which enabled us to establish
      cut-offs correlating with apoptosis rates. All five SK forms were associated with
      lower apoptosis rates compared with normal skin. A C3V2F score >10 and greater
      number of crypts and colours reflected a higher apoptosis rate, which implies a
      benign character of evolution. In contrast, the presence of irregular vessels on
      more than 50% of the lesion surface implied a lower rate of apoptosis and
      probably associated with a risk of malignant transformation. On the basis of
      dermoscopic information, we used multiple regression to establish a model for
      estimating the rate of apoptosis with a 0.7 prediction interval (approximately
      1S.D.). The new C3V2F score could be valuable for the clinical evaluation of
      possible SK prognosis and decisions regarding excision.

PMID- 22404842
TI  - New insights into the role of iron in the promotion of lipid oxidation in bulk
      oils containing reverse micelles.
AB  - Formation of physical structures, known as association colloids, in bulk oils can
      promote lipid oxidation. However, the cause of this accelerated lipid oxidation
      is unknown. Therefore, the aim of this study was to investigate whether
      transition metals were important prooxidants in bulk oils containing reverse
      micelles produced from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and water.
      The Fe(III) chelator deferoxamine (DFO) increased the oxidative stability of
      stripped soybean oil (SSO) containing reverse micelles from 2 to 7 days. Because
      phosphatidylcholine (1,2-dibutyl-sn-glycero-3-phosphocholine) that does not form
      reverse micelles is not prooxidative, these results suggest that the prooxidant
      activity of DOPC reverse micelles could be due to their ability to concentrate
      both endogenous iron and lipid hydroperoxides at the water-lipid interface,
      thereby increasing the ability of iron to decompose lipid hydroperoxides. DFO was
      also able to improve the activity of alpha-tocopherol and Trolox in SSO
      containing DOPC reverse micelles increasing the lag phase from 2 to 11 and 13
      days, respectively. DOPC reverse micelles decreased iron-promoted alpha
      tocopherol and Trolox decomposition and decreased the ability of alpha-tocopherol
      and Trolox to decrease Fe(III) concentrations. Overall, these results suggest
      that iron is an important prooxidant in bulk oils containing reverse micelles;
      therefore, finding ways to control iron reactivity in association colloids could
      provide new technologies to increase the oxidative stability of oils.

PMID- 22404843
TI  - Existing medications among non-pregnancy-related listeriosis patients in England,
      2007-2009.
AB  - To identify which medications were most commonly taken by non-pregnancy-related
      listeriosis patients prior to illness, we compared the medications reported by
      512 cases identified via national surveillance in England between 2007 and 2009
      with national prescription data, using British National Formulary (BNF) coding.
      Relative risks and corresponding confidence intervals were calculated, as
      appropriate, for BNF chapters and sections. Among listeriosis cases, the rates
      for cytotoxic drugs, drugs affecting the immune response and corticosteroids were
      significantly higher than for other medications. However, interactions between
      medications and how medications might confound or be confounded by concurrent
      medical conditions need to be investigated further. Nevertheless our findings
      suggest that targeting food-safety advice to prevent this foodborne disease in
      certain treatment groups is warranted.

PMID- 22404844
TI  - Deep sternal wound infection after open heart surgery--reconstructive options.
AB  - OBJECTIVES: The management of sternal defects arisen after deep sternal wound
      infection is challenging and often requires extensive interdisciplinary teamwork
      between plastic and thoracic surgeons. In this study, the published literature on
      methods used to reconstruct sternal defects arisen as a result of deep sternal
      wound infection after open-heart surgery will be reviewed. DESIGN: The Cochrane,
      Embase, PubMed, and SveMed + databases were searched in December 2011. Only
      papers regarding treatment of deep sternal wound infection after open-heart
      surgery in adults were included. RESULTS: The literature search identified 224
      original papers that met the inclusion criteria. The majority dealt with surgical
      techniques. None of the studies regarding reconstructive options were designed as
      randomized controlled trials, and the levels of evidence are generally low.
      CONCLUSION: The treatment of deep sternal wound infection has evolved
      considerably, but there is still little consensus regarding optimal surgical
      management and a general lack of a standard treatment protocol. The use of muscle
      flap transposition is well documented. Recent studies recommend the use of
      topical negative pressure therapy as an adjunct to surgical reconstruction.

PMID- 22404845
TI  - Temporary emergency pacing--an orphan in district hospitals.
AB  - This editorial discusses a report on the 1 year experience with temporary pacing,
      especially in the emergency setting, in several Norwegian district hospitals. The
      vast majority of the patients received transvenous temporary pacing, and the
      majority of leads were placed by noncardiologists. The procedure times were long
      and complications were frequent. The organization of emergency pacing is
      discussed, and we suggest that unless qualified physicians can establish
      transvenous pacing, the patients who need that should be transferred with
      transcutaneous pacing as back-up during transport to a hospital with more
      available competence. Ideally, those who need pacing immediately, including those
      who need permanent pacing, should be offered permanent implantation on a 24
      hours/7 days per week base.

PMID- 22404846
TI  - In vivo microscopy of targeted vessel occlusion employing acoustic droplet
      vaporization.
AB  - OBJECTIVE: Embolotherapy is a potential means to treat a variety of cancers. Our
      approach-gas embolotherapy-introduces the droplets upstream from the tumor and
      then acoustically activates them to form bubbles for occlusion-a process known as
      ADV. We wanted to provide the first optical documentation of ADV, lodged bubbles,
      or vessel occlusion in vivo. METHODS: We used the rat cremaster muscle for in
      vivo microscopy. Perfluorocarbon droplets were administered into the aortic arch.
      Ultrasound exposures in the cremaster induced vaporization. The cremaster was
      examined pre- and post-exposure for ADV-related effects. Two sets of experiments
      compared the effect of exposure in the capillaries versus the first order
      arteriole. RESULTS: Bubbles that lodge following capillary exposure are
      significantly larger (76 MUm mean length, 36 MUm mean diameter) than those
      following feeder vessel exposure (25 MUm mean length, 11 MUm mean diameter).
      Despite the differing sizes in bubbles, the ratio of bubble length to the
      hydraulic diameter of all lodged bubbles was 2.11 (+/-0.65; n = 112), which
      agrees with theoretical predictions and experimental observations. CONCLUSIONS:
      Our results provide the first optical evidence of targeted vessel occlusion
      through ADV. These findings could lay the groundwork for the advancement of gas
      embolotherapy.

PMID- 22404847
TI  - Synthesis and biological evaluation of N-aryl-4-aryl-1,3-thiazole-2-amine
      derivatives as direct 5-lipoxygenase inhibitors.
AB  - Biological evaluation of N-aryl-4-aryl-1,3-thiazole-2-amine derivatives was
      examined for anti-inflammatory activity in in vitro and in vivo assays. The
      thiazole compounds showed direct inhibition of 5-lipoxygenase (LOX) that is a key
      enzyme of leukotrienes synthesis and involved in the inflammation-related
      diseases, including asthma and rheumatoid arthritis. To optimize biological
      activity, we synthesized 1,3-thiazole-2-amine derivatives and investigated for
      structure and activity relationship. Especially, N-(3,5-dimethylphenyl)-4-(4
      chlorophenyl)-1,3-thiazole-2-amine was shown to have a potent anti-inflammatory
      activity as a 5-LOX inhibitor.

PMID- 22404848
TI  - Qualitative descriptive study exploring schizophrenia and the everyday effect of
      medication-induced weight gain.
AB  - Weight gain and obesity are serious side effects of the medications used to
      manage psychotic disorders and successful, long-term weight loss interventions
      are not yet available. One reason for this may be that current interventions are
      designed without consideration of the patient's perspective. The purpose of this
      study was to explore the subjective experience of weight and lifestyle from the
      perspective of people with schizophrenia. A qualitative, constructivist research
      design was used and conversational interviews were conducted with 18 purposefully
      recruited participants from an outpatient clinic at a psychiatric hospital in
      Eastern Ontario. Data were analysed according to the method of constant
      comparison and three central themes emerged: a life altering diagnosis, weight
      management as complex, and today's experiences shape tomorrow's outcomes. Weight
      management was seen as difficult yet important to the participants. The findings
      of this study provide insight into the views and opinions of the participants
      regarding weight and lifestyle and may be used to support the design of tailored
      heath initiatives for persons with mental illness.

PMID- 22404849
TI  - Switching iron-deficient whole blood donors to plateletpheresis.
AB  - BACKGROUND: Iron deficiency is a frequent side effect of whole blood (WB)
      donation. In contrast, less red blood cell loss and therefore less iron loss
      results from plateletpheresis. STUDY DESIGN AND METHODS: WB donors presenting a
      decrease in either hemoglobin (Hb) or ferritin levels were offered to switch to
      plateletpheresis with or without iron supplementation. We analyzed the effect of
      this intervention on deferral rates for an insufficient Hb level in 168 donors.
      Further, we assessed how this intervention affected Hb and ferritin levels,
      anemia occurrence, and platelet (PLT) concentrate yields in the donors who
      presented at least four successive times for thrombapheresis. RESULTS: Switching
      WB donors to repetitive plateletpheresis procedures resulted in an increase of
      median Hb (+12 g/L, p < 0.001) and ferritin (+15.5 ng/mL, p = 0.002) values.
      Anemia and deferral rates were reduced by 23% (p = 0.004) and 13% (p < 0.001).
      Between high- and low-frequency apheresis donors, no significant differences in
      Hb and ferritin levels were found. Similarly, discrepancies in Hb and ferritin
      values between donors that adopted iron supplementation and those who did not
      were insignificant. The median PLT concentrate yield was 5.43 * 10(11) PLTs.
      CONCLUSION: Switching iron-deficient WB donors to plateletpheresis was an
      effective intervention that permitted us to correct low Hb and ferritin levels
      while retaining donors in our pool.

PMID- 22404850
TI  - Evidence that Yih1 resides in a complex with ribosomes.
AB  - Adjusting protein synthesis by phosphorylating eukaryotic translation initiation
      factor 2 (eIF2alpha) is a major mechanism by which eukaryotes adapt to and
      overcome stress. The eIF2alpha kinase Gcn2 is essential for overcoming amino acid
      starvation in all eukaryotes. We have shown that to sense starvation, the Gcn2
      RWD domain must directly contact its effector protein, Gcn1, and both must bind
      to the ribosome, suggesting that starvation is sensed within a Gcn1-Gcn2-ribosome
      complex. The mammalian protein IMPACT, highly expressed in neurons, and its yeast
      orthologue yeast IMPACT homologue (Yih1) harbour an RWD domain with Gcn1-binding
      activity. We have shown that Yih1 downregulates Gcn2 by competing with Gcn2 for
      Gcn1-binding. Here, we provide evidence that Yih1 forms a complex with ribosomes.
      In velocity sedimentation assays, overexpressed glutathione S-transferase (GST)
      tagged Yih1 cosedimented with polyribosomes independently of Gcn1. Reduction of
      polyribosomes to monosomes concomitantly decreased GST-Yih1 sedimentation in the
      heavy fractions where polyribosomes are normally found. Furthermore, GST-Yih1
      coprecipitated large ribosomal protein Rpl39 independently of Gcn1. GST-Yih1
      overexpression did not significantly affect Gcn1-ribosome or Gcn2-ribosome
      cosedimentation. myc-tagged Yih1 expressed from its own promoter cosedimented
      with polyribosomes independently of Gcn1, indicating that Yih1-ribosome
      interaction occurs under physiological conditions. GST-IMPACT cosedimented with
      yeast ribosomes and coprecipitated Rpl39 in a Gcn1-independent fashion,
      suggesting that Yih1/IMPACT-ribosome association is evolutionarily conserved.
      Moreover, GST-IMPACT coprecipitated actin as found for GST-Yih1. Taken together,
      our findings strongly suggest that IMPACT/Yih1 associates with ribosomes and that
      these ribosomes may simultaneously carry Gcn1 and Gcn2. Close physical proximity
      of Yih1 to the Gcn1-Gcn2-ribosome complex would allow cells to quickly inhibit
      Gcn2 whenever or wherever necessary.

PMID- 22404851
TI  - Intraindividual cognitive decline using a brief computerized cognitive screening
      test.
AB  - BACKGROUND: Progressive intraindividual decline in memory and cognition is
      characteristic of dementia and may be useful in detecting very early Alzheimer's
      disease pathology. METHODS: This study evaluated the slopes of cognitive
      performance over a 12-month period in 263 healthy, community-dwelling, adult
      volunteers aged >=50 years. Participants completed a brief computerized battery
      of cognitive tests (CogState) at baseline and during 3-, 6-, 9-, and 12-month
      follow-up assessments. Linear mixed models were used to estimate age-adjusted
      mean slopes and 95% confidence intervals of change for each of the cognitive
      measures. RESULTS: By defining age-adjusted mean slopes, and 95% confidence
      intervals for a measure of episodic memory, individuals with greater than
      expected decline (equal to or lower than the fifth percentile level of decline)
      were identified. From these, four individuals completed a full medical,
      neurologic, and neuropsychological evaluation, with none of them fulfilling
      criteria for mild cognitive impairment, but three (75%) having positive amyloid
      positron emission tomographic scans. CONCLUSIONS: Intraindividual decline in
      cognitive performance can be detected in otherwise healthy, community-dwelling,
      older persons, and this may deserve further study as a potential indicator of
      early Alzheimer's disease pathology.

PMID- 22404852
TI  - Fornix integrity and hippocampal volume predict memory decline and progression to
      Alzheimer's disease.
AB  - BACKGROUND: The fornix is the predominant outflow tract of the hippocampus, a
      brain region known to be affected early in the course of Alzheimer's disease
      (AD). The aims of the present study were to: (1) examine the cross-sectional
      relationship between fornix diffusion tensor imaging (DTI) measurements
      (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity, and radial
      diffusivity), hippocampal volume, and memory performance, and (2) compare fornix
      DTI measures with hippocampal volumes as predictors of progression and transition
      from amnestic mild cognitive impairment to AD dementia. METHODS: Twenty-three
      mild cognitive impairment participants for whom hippocampal volumetry and DTI
      were conducted at baseline received detailed evaluations at baseline; 3, 6, and
      12 months; and 2.5 years. Six participants converted to AD over the follow-up
      period. Fornix and posterior cingulum DTI measurements and hippocampal volumes
      were ascertained using manual measures. Random effects models assessed each of
      the neuroimaging measures as predictors of decline on the Mini-Mental State
      Examination, Clinical Dementia Rating-sum of boxes, and memory z scores; receiver
      operating characteristic analyses examined the predictive value for conversion to
      AD. RESULTS: There was a significant correlation between fornix FA and
      hippocampal volumes. However, only the fornix measurements (FA, MD, radial
      diffusivity, and axial diffusivity) were cross-sectionally correlated with memory
      z scores. Both fornix FA and hippocampal volumes were predictive of memory
      decline. Individually, fornix FA and MD and hippocampal volumes were very good
      predictors of progression, with likelihood ratios >83, and better than 90%
      accuracy. CONCLUSION: Fornix FA both cross-sectionally correlated with and
      longitudinally predicted memory decline and progression to AD. Manually drawn
      region of interest within the fornix shows promise comparable with hippocampal
      volume as a predictive biomarker of progression, and this finding warrants
      replication in a larger study.

PMID- 22404853
TI  - Psychosocial stress at work is associated with increased dementia risk in late
      life.
AB  - OBJECTIVE: To test the hypothesis that high job stress during working life might
      lead to an increased risk of dementia and Alzheimer's disease (AD) in late life.
      METHODS: A dementia-free cohort of 913 community dwellers, aged 75+ years, from
      the Kungsholmen Project, a population-based follow-up study carried out in
      Stockholm, Sweden, was followed up for an average of 6 years to detect incident
      dementia and AD (third revised Diagnostic and Statistical Manual of Mental
      Disorders). Information on the lifespan work activities was collected.
      Psychological stress at work was estimated for the longest period of occupation
      as well as for all occupations by using a validated psychosocial job exposure
      matrix on two dimensions: job control and job demands. Cox proportional hazards
      models were used to estimate the hazard ratios (HRs) and 95% confidence intervals
      (CIs) of dementia and AD in relation to different levels of job stress. RESULTS:
      Low level of job control was associated with higher multivariate adjusted risk of
      dementia (HR = 1.9, 95% CI: 1.2-3.0) and AD (HR = 2.2, 95% CI: 1.2-3.9). Low
      level of job demands alone was not significantly associated with increased
      dementia risk. When the two dimensions were combined into a four-category job
      strain model, both high job strain (low control/high demands) and passive strain
      (both low control and demands) were related to higher risk of dementia and AD as
      compared with active job strain (both high). Vascular disorders did not mediate
      the observed associations. CONCLUSION: Lifelong work-related psychosocial stress,
      characterized by low job control and high job strain, was associated with
      increased risk of dementia and AD in late life, independent of other known risk
      factors.

PMID- 22404854
TI  - 2012 Alzheimer's disease facts and figures.
AB  - This report provides information to increase understanding of the public health
      impact of Alzheimer's disease (AD). Topics addressed include incidence,
      prevalence, mortality rates, health expenditures and costs of care, and effect on
      caregivers and society. The report also explores issues that arise when people
      with AD and other dementias live alone. The characteristics, risks, and unmet
      needs of this population are described. An estimated 5.4 million Americans have
      AD, including approximately 200,000 age <65 years who comprise the younger-onset
      AD population. Over the coming decades, the aging of the baby boom generation is
      projected to result in an additional 10 million people with AD. Today, someone in
      America develops AD every 68 seconds. By 2050, there is expected to be one new
      case of AD every 33 seconds, or nearly a million new cases per year, and AD
      prevalence is projected to be 11 million to 16 million. Dramatic increases in the
      number of "oldest-old" (those age >=85 years) across all racial and ethnic groups
      are expected to contribute to the increased prevalence of AD. AD is the sixth
      leading cause of death in the United States and the fifth leading cause of death
      in Americans age >=65 years. Although the proportions of deaths due to other
      major causes of death have decreased in the last several years, the proportion
      due to AD has risen significantly. Between 2000 and 2008, the proportion of
      deaths due to heart disease, stroke, and prostate cancer decreased by 13%, 20%,
      and 8%, respectively, whereas the proportion due to AD increased by 66%. In 2011,
      more than 15 million family members and other unpaid caregivers provided an
      estimated 17.4 billion hours of care to people with AD and other dementias, a
      contribution valued at more than $210 billion. Medicare payments for services to
      beneficiaries age >=65 years with AD and other dementias are three times as great
      as payments for beneficiaries without these conditions, and Medicaid payments are
      19 times as great. In 2012, payments for health care, long-term care, and hospice
      services for people age >=65 years with AD and other dementias are expected to be
      $200 billion (not including the contributions of unpaid caregivers). An estimated
      800,000 people with AD (one in seven) live alone, and up to half of them do not
      have an identifiable caregiver. People with dementia who live alone are exposed
      to risks that exceed the risks encountered by people with dementia who live with
      others, including inadequate self-care, malnutrition, untreated medical
      conditions, falls, wandering from home unattended, and accidental deaths.

PMID- 22404855
TI  - Antigen-presenting genes and genomic copy number variations in the Tasmanian
      devil MHC.
AB  - BACKGROUND: The Tasmanian devil (Sarcophilus harrisii) is currently under threat
      of extinction due to an unusual fatal contagious cancer called Devil Facial
      Tumour Disease (DFTD). DFTD is caused by a clonal tumour cell line that is
      transmitted between unrelated individuals as an allograft without triggering
      immune rejection due to low levels of Major Histocompatibility Complex (MHC)
      diversity in Tasmanian devils. RESULTS: Here we report the characterization of
      the genomic regions encompassing MHC Class I and Class II genes in the Tasmanian
      devil. Four genomic regions approximately 960 kb in length were assembled and
      annotated using BAC contigs and physically mapped to devil Chromosome 4q. 34
      genes and pseudogenes were identified, including five Class I and four Class II
      loci. Interestingly, when two haplotypes from two individuals were compared,
      three genomic copy number variants with sizes ranging from 1.6 to 17 kb were
      observed within the classical Class I gene region. One deletion is particularly
      important as it turns a Class Ia gene into a pseudogene in one of the haplotypes.
      This deletion explains the previously observed variation in the Class I allelic
      number between individuals. The frequency of this deletion is highest in the
      northwestern devil population and lowest in southeastern areas. CONCLUSIONS: The
      third sequenced marsupial MHC provides insights into the evolution of this
      dynamic genomic region among the diverse marsupial species. The two sequenced
      devil MHC haplotypes revealed three copy number variations that are likely to
      significantly affect immune response and suggest that future work should focus on
      the role of copy number variations in disease susceptibility in this species.

PMID- 22404857
TI  - Under-grading of <4 cm renal masses on renal biopsy.
AB  - What's known on the subject? and What does the study add? It is well documented
      that biopsy of small renal masses is inaccurate and tends to under-estimate
      tumour grade compared with surgical specimens. To our knowledge there has not
      been a study showing grading discrepancy between biopsy and surgical excision in
      a large population-based cohort. OBJECTIVE: To determine whether differences
      exist in tumour grade between patients who undergo partial nephrectomy (PN) and
      those who undergo ablation for renal tumours. PATIENTS AND METHODS: Data was
      obtained using the Surveillance, Epidemiology and End Results database. Patients
      with solitary renal tumours of <4 cm treated with ablation or PN and with renal
      cell carcinoma (RCC) histopathology were identified. Tissue diagnosis in the
      ablation specimens was obtained from biopsy reports, whereas tissue from PN
      specimens was determined from surgical pathology. Variables analysed included:
      year of diagnosis, age, sex, race/ethnicity, marital status, population density,
      education, poverty level, and tumour size. Stacked bar graphs were created to
      compare the distributions of grade and histology between the groups. Multinomial
      logistic regression was used to determine factors independently associated with
      grade. RESULTS: In all, 7704 (87.4%) patients underwent PN and 1114 (12.6%)
      underwent either radiofrequency ablation or cryoablation. The PN patients were
      younger at diagnosis (59 vs 68 years, P < 0.001), more likely to be married (70%
      vs 64%, P < 0.001), and had smaller tumours (2.4 vs 2.6 cm, P < 0.001). There
      were no differences in the distribution of histology between the PN and ablation
      groups. Tumour grade was significantly lower in tumours treated with ablation.
      Compared with grade 1 disease, those undergoing ablation were 30% less likely to
      have grade 2 (P < 0.001), 30% less likely to have grade 3 (P < 0.001), and 92%
      less likely to have grade 4 disease (P < 0.01) than those having PN. CONCLUSIONS:
      There is a strong association between grade and treatment type in patients with
      small renal masses after controlling for baseline characteristics. As grade is
      determined by different methods, we think that this shows systematic under
      grading in biopsy of small renal masses.

PMID- 22404856
TI  - Relevance of animal models to human tardive dyskinesia.
AB  - Tardive dyskinesia remains an elusive and significant clinical entity that can
      possibly be understood via experimentation with animal models. We conducted a
      literature review on tardive dyskinesia modeling. Subchronic antipsychotic drug
      exposure is a standard approach to model tardive dyskinesia in rodents. Vacuous
      chewing movements constitute the most common pattern of expression of purposeless
      oral movements and represent an impermanent response, with individual and strain
      susceptibility differences. Transgenic mice are also used to address the
      contribution of adaptive and maladaptive signals induced during antipsychotic
      drug exposure. An emphasis on non-human primate modeling is proposed, and past
      experimental observations reviewed in various monkey species. Rodent and primate
      models are complementary, but the non-human primate model appears more
      convincingly similar to the human condition and better suited to address
      therapeutic issues against tardive dyskinesia.

PMID- 22404858
TI  - Particulate matter exposure during pregnancy is associated with birth weight, but
      not gestational age, 1962-1992: a cohort study.
AB  - BACKGROUND: Exposure to air pollutants is suggested to adversely affect fetal
      growth, but the evidence remains inconsistent in relation to specific outcomes
      and exposure windows. METHODS: Using birth records from the two major maternity
      hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we
      constructed a database of all births to mothers resident within the city. Weekly
      black smoke exposure levels from routine data recorded at 20 air pollution
      monitoring stations were obtained and individual exposures were estimated via a
      two-stage modeling strategy, incorporating temporally and spatially varying
      covariates. Regression analyses, including 88,679 births, assessed potential
      associations between exposure to black smoke and birth weight, gestational age
      and birth weight standardized for gestational age and sex. RESULTS: Significant
      associations were seen between black smoke and both standardized and
      unstandardized birth weight, but not for gestational age when adjusted for
      potential confounders. Not all associations were linear. For an increase in whole
      pregnancy black smoke exposure, from the 1(st) (7.4 MUg/m(3)) to the 25(th) (17.2
      MUg/m(3)), 50(th) (33.8 MUg/m(3)), 75(th) (108.3 MUg/m(3)), and 90(th) (180.8
      MUg/m(3)) percentiles, the adjusted estimated decreases in birth weight were 33 g
      (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant
      interaction was observed between socio-economic deprivation and black smoke on
      both standardized and unstandardized birth weight with increasing effects of
      black smoke in reducing birth weight seen with increasing socio-economic
      disadvantage. CONCLUSIONS: The findings of this study progress the hypothesis
      that the association between black smoke and birth weight may be mediated through
      intrauterine growth restriction. The associations between black smoke and birth
      weight were of the same order of magnitude as those reported for passive smoking.
      These findings add to the growing evidence of the harmful effects of air
      pollution on birth outcomes.

PMID- 22404859
TI  - Specific tumor-stroma interactions of EBV-positive Burkitt's lymphoma cells in
      the chick chorioallantoic membrane.
AB  - BACKGROUND: Burkitt's lymphoma (BL) is an aggressive Non-Hodgkin lymphoma.
      Epstein-Barr Virus (EBV) is able to transform B cells and is a causative
      infectious agent in BL. The precise role of EBV in lymphoma progression is still
      unclear. Most investigations have concentrated on cell autonomous functions of
      EBV in B cells. Functions of the local environment in BL progression have rarely
      been studied, mainly due to the lack of appropriate in vivo models. Therefore, we
      inoculated different human BL cell-lines onto the chorioallantoic membrane (CAM)
      of embryonic day 10 (ED10) chick embryos and re-incubated until ED14 and ED17.
      RESULTS: All cell-lines formed solid tumors. However, we observed strong
      differences in the behavior of EBV+ and EBV- cell-lines. Tumor borders of EBV+
      cells were very fuzzy and numerous cells migrated into the CAM. In EBV- tumors,
      the borders were much better defined. In contrast to EBV- cells, the EBV+ cells
      induced massive immigration of chick leukocytes at the tumor borders and the
      development of granulation tissue with large numbers of blood vessels and
      lymphatics, although the expression of pro- and anti-angiogenic forms of Vascular
      Endothelial Growth Factors/receptors was the same in all BL cell-lines tested.
      The EBV+ cell-lines massively disseminated via the lymphatics and completely
      occluded them. CONCLUSIONS: Our data suggest that the EBV+ cells attract pro
      angiogenic leukocytes, which then induce secondary tumor-stroma interactions
      contributing to the progression of BL. We show that the CAM is a highly suitable
      in vivo model to study the differential behavior of BL cell-lines.

PMID- 22404860
TI  - Phaeohyphomycosis due to Alternaria infectoria: a single-center experience with
      utility of PCR for diagnosis and species identification.
AB  - The term phaeohyphomycosis refers to a rare group of fungal infections
      characterized by the presence of dark-walled hyphae or yeast-like cells in
      affected tissues. Herein, we report on the clinical and epidemiological
      characteristics of six cases of phaeohyphomycosis due to Alternaria spp. that
      occurred in our hospital over a 30-month period (from January 2008 to June 2010).
      Interestingly, whereas histopathological examinations were positive and fungal
      cultures yielded molds in all cases, mycological identification using
      conventional phenotypic methods was never possible despite prolonged incubation
      of the isolates. Identification of Alternaria infectoria species complex was
      obtained for each isolate by amplification and sequencing of the internal
      transcribed spacer of the ribosomal DNA (ITS rDNA). All patients had favourable
      outcomes following the introduction of azole-based antifungal therapy. This case
      series describes the clinical course of these six patients and highlights the
      utility of molecular identification to help in the identification of the
      etiologic agent when classical mycological methods have failed.

PMID- 22404861
TI  - Reflections of young people who have had a first episode of psychosis: what
      attracted them to use alcohol and illicit drugs?
AB  - AIM: To identify factors that contribute to the initiation of alcohol and street
      drug use from the perspective of people who were enrolled in early intervention
      programmes for a first episode of psychosis. METHOD: Eight focus groups were
      conducted involving an average of four to six participants per group, with each
      group consisting of young people who met provincial inclusion criteria for early
      intervention programmes. Thematic analysis was used to systematically code
      transcripts from the focus groups for concepts, patterns and themes related to
      early use of illicit substances. RESULTS: Participants included 45 young people
      diagnosed with affective psychosis or non-affective spectrum disorders. Seventy
      three percent were male, with a median age of 23 years. In general, substance use
      was an important topic that emerged across all focus groups. Participants talked
      about three main factors attracting them to initiate use of substances, most
      predominantly cannabis: (i) using within a social context; (ii) using as a self
      medication strategy; and (iii) using to alter their perceptions. CONCLUSIONS: The
      need for social relationships, coping strategies and pleasurable experiences
      appear to be important reasons for initiating substance use. Additional research
      is needed to identify whether prodromal youth report the same factors that
      attract them to initiate use in order to develop more effective prevention
      strategies.

PMID- 22404862
TI  - Supporting the massive scale-up of antiretroviral therapy: the evolution of
      PEPFAR-supported treatment facilities in South Africa, 2005-2009.
AB  - BACKGROUND: South Africa has an estimated 1.5 million persons in need of
      antiretroviral therapy (ART). In 2004, the South African government began
      collaborating with the United States President's Emergency Plan for AIDS Relief
      (PEPFAR) to increase access to ART. We determined how PEPFAR treatment support
      changed from 2005-2009. METHODS: In order to describe the change in number and
      type of PEPFAR-supported ART facilities, we analyzed routinely collected program
      monitoring data from 2005-2009. The collected data included the number, type and
      province of facilities as well as the number of patients receiving ART at each
      facility. RESULTS: The number of PEPFAR-supported facilities providing ART
      increased from 184 facilities in 2005 to 1,469 facilities in 2009. From 2005-2009
      the number of PEPFAR-supported government facilities increased 10.1 fold from 54
      to 546 while the number of PEPFAR-supported NGO facilities (including general
      practitioner and NGO facilities) increased 6.2 fold from 114 to 708. In 2009 the
      total number of persons treated at PEPFAR-supported NGO facilities was 43,577
      versus 501,089 persons at PEPFAR-supported government facilities. Overall, the
      median number of patients receiving ART per site increased from 81 in 2005 to 136
      in 2009. CONCLUSIONS: To mitigate the gap between those needing and those
      receiving ART, more facilities were supported. The proportion of government
      facilities supported and the median number of persons treated at these facilities
      increased. This shift could potentially be sustainable as government sites reach
      more individuals and receive government funding. These results demonstrate that
      PEPFAR was able to support a massive scale-up of ART services in a short period
      of time.

PMID- 22404863
TI  - Early vocalization of preterm infants with extremely low birth weight (ELBW),
      Part I: From birth to expansion stage.
AB  - The vocalization of preterm infants with extremely low birth weight (ELBW) up to
      the expansion stage was systematically described and compared with those of
      healthy full-term infants. The sample consisted of 18 preterm ELBW infants and
      the control group of 11 full-term infants. The follow-up was performed
      intensively using video-recordings. The vocalization of the preterm and full-term
      infants was analyzed quantitatively according to the categorical stages created
      by Oller. A descriptive analysis of all the vocalizations produced by the infants
      was performed. The preterm infants entered the primitive articulation stage later
      than the full-term infants and failed to produce more skills during that stage.
      According to this sample, there was no difference in entering the expansion
      stage, but the preterm infants failed to produce more skills than the full-term
      infants. The number of vocalization acts varied differently by age between the
      groups.

PMID- 22404864
TI  - Early vocalization of preterm infants with extremely low birth weight (ELBW),
      Part II: From canonical babbling up to the appearance of the first word.
AB  - The aim of this study was to systematically describe the preverbal development of
      preterm infants from canonical babbling up to the first word and to compare it
      with that of healthy full-term infants. In addition, the amount of vocalization
      between the preterm and full-term groups was compared. The sample consisted of 18
      preterm infants with extremely low birth weight and 11 full-term infants. The
      development of preverbal vocalization before variegated babbling did not differ
      between the groups. Instead, the preterm infants failed to produce more different
      kinds of canonical syllable types than the full-term infants. However, they
      showed a larger variance of variegated babbling skills and remained in the
      babbling phase longer before reaching the first meaningful word compared with the
      full-term infants. Following the onset of canonical babbling, the preterm infants
      produced fewer vocalizations than the full-term infants and they reached the
      first word later than the full-term infants.

PMID- 22404865
TI  - The use of subject-verb agreement and verb argument structure in monolingual and
      bilingual children with specific language impairment.
AB  - This study investigates the use of subject-verb agreement and verb argument
      structure in the spoken Dutch of monolingual Dutch children with specific
      language impairment (SLI) and bilingual Frisian-Dutch children with SLI. Both SLI
      groups appeared to be less efficient in their use of subject-verb agreement and
      verb argument structure than the control group (consisting of monolingual
      typically developing Dutch children matched on mean length of utterance in
      morphemes) in that they showed significantly more agreement errors as well as a
      relation between verb agreement structure complexity and omission, a relation
      that the typically developing children failed to show. Furthermore, no
      significant differences were found between the monolingual and the bilingual SLI
      group. These findings indicate that subject-verb agreement and verb argument
      structure are both affected in SLI, but not more severely in bilinguals than in
      monolinguals.

PMID- 22404866
TI  - Analogical reasoning in children with specific language impairment.
AB  - Usage-based theory considers analogical reasoning as a cognitive process required
      in language development. We hypothesized that difficulties with analogical
      reasoning could hinder the abstraction of construction schemas, thus slowing down
      morphosyntactic development for children with specific language impairment (SLI).
      We also hypothesized, in accordance with usage-based theory, that the same
      analogy mechanism is shared by linguistic and non-linguistic processes. The
      current study investigated the performance of 15 children with SLI in comparison
      with age-matched peers on a non-linguistic analogical reasoning task. Our
      experimental setting targeted two prerequisites of analogical reasoning:
      structural alignment and the discovery of relational similarity in comparison
      with perceptual similarity. The results obtained are compatible with our
      hypotheses according to which children with SLI would encounter problems building
      more abstract construction schemas, related to difficulties with analogical
      reasoning. The study also shows that children with SLI have specific cognitive
      difficulties regardless of their linguistic development.

PMID- 22404867
TI  - Effect of timing and duration of salt treatment during growth of a fragrant rice
      variety on yield and 2-acetyl-1-pyrroline, proline, and GABA Levels.
AB  - In greenhouse experiments, Aychade, a fragrant rice variety, was grown under one
      level of salt solution (EC of 3800 +/- 400 MUS.cm(-1)) sufficient to induce salt
      stress in rice. Timing and duration of salt solution application varied according
      to the growth stages. 2-Acetyl-1-pyrroline (2AP), a characteristic flavor
      compound of fragrant rice as well as biogenetically related compounds, proline,
      and gamma-aminobutyric acid (GABA) were quantified. Salt treatments induced 2AP
      synthesis in the leaves, but the increase was often higher in the vegetative
      phase. This increase was correlated with proline level but not with that of GABA.
      Interestingly the grains from all the salt treated plants contained significantly
      higher levels of 2AP (733-998 MUg.kg(-1)) than those from the control (592
      MUg.kg(-1)). The highest 2AP synthesis occurred when the plants were subjected to
      salt treatment during whole vegetative or reproductive phases. However in the
      latter case crop yield decreased significantly.

PMID- 22404868
TI  - Risk factors associated with human brucellosis in the country of Georgia: a case
      control study.
AB  - Human brucellosis occurs when humans ingest or contact Brucella spp. from
      shedding animals or contaminated environments and food. In Georgia animal and
      human brucellosis is endemic, but the epidemiology has not been fully
      characterized. A case-control study was conducted in 2010 to identify risk
      factors for human brucellosis. Using multivariable logistic regression, the
      following risk factors were identified: animal-related work [odds ratio (OR)
      77.8, 90% confidence interval (CI) 4.7-1278], non-animal-related work (OR 12.7,
      90% CI 1.1-149), being unemployed or a pensioner (OR 13.1, 90% CI 1.7, 101),
      sheep ownership (OR 19.3, 90% CI 5.1-72.6), making dairy products (OR 12.4, 90%
      CI 1.4-113), living in eastern Georgia (Kakheti) (OR 278.1, 90% CI 9.5-8100), and
      being aged >44 years (OR 9.3, 90% CI 1.02-84.4). Education of at-risk groups
      about risk factors and control of disease in sheep may reduce the human disease
      risk. This is the first study of its kind in Georgia since the collapse of the
      Soviet Union.

PMID- 22404869
TI  - Host phylogeny and specialisation in parasitoids.
AB  - The host range of insect parasitoids and herbivores is influenced by both
      preference-related traits which mediate host choice behaviour, and performance
      related traits which mediate the physiological suitability of the consumer
      resource interaction. In a previous study, we characterised the influence of
      preference- and performance-related traits on the host range of the aphid
      parasitoid Binodoxys communis (Hymenoptera: Braconidae) and herein we build upon
      those data sets by mapping a series of these traits onto the phylogeny of the
      (aphid) host species. We found a strong effect of host phylogeny on overall
      parasitoid reproduction on the 20 host species tested, but no effect of the
      phylogeny of host plants of the aphids. We found an effect of aphid phylogeny on
      host acceptance and sting rates (related to preference) from behavioural
      observations and for pupal survivorship (related to performance), showing that
      both classes of traits show phylogenetic conservatism with respect to host
      species.

PMID- 22404870
TI  - An automatic wash method for dimethyl sulfoxide removal in autologous
      hematopoietic stem cell transplantation decreases the adverse effects related to
      infusion.
AB  - BACKGROUND: Products cryopreserved with dimethyl sulfoxide (DMSO) in stem cell
      transplant (SCT) often cause many adverse effects during their infusion (major
      cardiovascular events, dyspnea ... even death). These are especially frequent in
      pediatric patients. We tested if a fully automated and closed wash procedure
      (Sepax S-100, Biosafe) allowed us to maintain the absolute CD34+ cell number,
      cell viability, and engraftment potential, decreasing the untoward reactions.
      STUDY DESIGN AND METHODS: Forty-six washes of DMSO cryopreserved peripheral blood
      hematopoietic progenitor (HP) apheresis were studied. Blood aliquots were taken
      both after thawing and after washing to assess the total nucleated and CD34+ cell
      counts, as well as cell viability. The washed products were infused in 26
      autologous SCTs (ASCTs). Results were compared with the 53 previous SCTs
      performed without DMSO removal. RESULTS: After washing there were no significant
      differences between the pre- and postwashing CD34+ cell counts (p=0.08) or
      viability (p=0.68). No significant differences were observed between washed and
      nonwashed infusions in relation to the day of the neutrophil (p=0.46) and
      platelet (p=0.26) engraftment. One adverse event, abdominal pain, occurred during
      the washed cells infusions. When compared with the 14 untoward reactions that
      took place during the nonwashed HP infusions, significance was reached
      (p=0.00043). CONCLUSIONS: The automatic method described is effective in terms of
      CD34+ cell recovery and viability in ASCT. Moreover, Sepax decreased
      significantly the untoward reactions during the infusion.

PMID- 22404871
TI  - Aging brain microenvironment decreases hippocampal neurogenesis through Wnt
      mediated survivin signaling.
AB  - Accumulating evidence suggests that adult hippocampal neurogenesis relies on the
      controlled and continued proliferation of neural progenitor cells (NPCs). With
      age, neurogenesis decreases through mechanisms that remain unclear but are
      believed to involve changes in the NPC microenvironment. Here, we provide
      evidence that NPC proliferation in the adult brain is in part regulated by
      astrocytes via Wnt signaling and that this cellular cross-talk is modified in the
      aging brain, leading to decreased proliferation of NPCs. Furthermore, we show
      that astrocytes regulate the NPC cell cycle by acting on the expression levels of
      survivin, a known mitotic regulator. Among cell cycle genes found down-regulated
      in aged NPCs, survivin was the only one that restored NPC proliferation in the
      aged brain. Our results provide a mechanism for the gradual loss of neurogenesis
      in the brain associated with aging and suggest that targeted modulation of
      survivin expression directly or through Wnt signaling could be used to stimulate
      adult neurogenesis.

PMID- 22404872
TI  - The Influence of verbalization on the pattern of cortical activation during
      mental arithmetic.
AB  - BACKGROUND: The aim of the present functional magnetic resonance imaging (fMRI)
      study at 3 T was to investigate the influence of the verbal-visual cognitive
      style on cerebral activation patterns during mental arithmetic. In the domain of
      arithmetic, a visual style might for example mean to visualize numbers and
      (intermediate) results, and a verbal style might mean, that numbers and
      (intermediate) results are verbally repeated. In this study, we investigated,
      first, whether verbalizers show activations in areas for language processing, and
      whether visualizers show activations in areas for visual processing during mental
      arithmetic. Some researchers have proposed that the left and right intraparietal
      sulcus (IPS), and the left angular gyrus (AG), two areas involved in number
      processing, show some domain or modality specificity. That is, verbal for the
      left AG, and visual for the left and right IPS. We investigated, second, whether
      the activation in these areas implied in number processing depended on an
      individual's cognitive style. METHODS: 42 young healthy adults participated in
      the fMRI study. The study comprised two functional sessions. In the first
      session, subtraction and multiplication problems were presented in an event
      related design, and in the second functional session, multiplications were
      presented in two formats, as Arabic numerals and as written number words, in an
      event-related design. The individual's habitual use of visualization and
      verbalization during mental arithmetic was assessed by a short self-report
      assessment. RESULTS: We observed in both functional sessions that the use of
      verbalization predicts activation in brain areas associated with language
      (supramarginal gyrus) and auditory processing (Heschl's gyrus, Rolandic
      operculum). However, we found no modulation of activation in the left AG as a
      function of verbalization. CONCLUSIONS: Our results confirm that strong
      verbalizers use mental speech as a form of mental imagination more strongly than
      weak verbalizers. Moreover, our results suggest that the left AG has no specific
      affinity to the verbal domain and subserves number processing in a modality
      general way.

PMID- 22404873
TI  - Influence of variable domain glycosylation on anti-neutrophil cytoplasmic
      autoantibodies and anti-glomerular basement membrane autoantibodies.
AB  - BACKGROUND: The pathophysiological significance of variable region glycosylation
      of autoantibodies is still unclear. In the current study, the influence of the
      variable region N-linked oligosaccharides on the reactivity of three autoantibody
      specificities was investigated with Sambucus nigra agglutinin (SNA), which mainly
      binds to oligosaccharides with terminal alpha2, 6-linked sialic acid on the
      variable region of IgG. METHODS: Twenty-seven patients with serum positive anti
      neutrophil cytoplasmic autoantibodies (ANCA) against myeploperoxidase (MPO) or
      proteinase 3 (PR3), or autoantibodies against glomerular basement membrane (GBM)
      were included. Total IgG was isolated and separated into non-SNA-binding and SNA
      binding fractions with SNA affinity chromatography. Antigen-specific IgG was
      purified by immunoaffinity chromatography. RESULTS: At the same concentration of
      IgG, the antigen binding level of non-SNA-binding IgG was significantly lower
      than that of SNA-binding IgG for MPO-ANCA (absorbance value at 405 nm, 0.572 +/-
      0.590 vs. 0.962 +/- 0.670, P < 0.001) and for PR3-ANCA (0.362 +/- 0.530 vs. 0.560
      +/- 0.531, P = 0.003). The antigen binding level of non-SNA-binding IgG was
      significantly higher than that of SNA-binding IgG for anti-GBM antibodies (1.301
      +/- 0.594 vs. 1.172 +/- 0.583, P = 0.044). The level of variable region
      glycosylation of total IgG was significantly lower than that of affinity-purified
      MPO-ANCA (1.021 +/- 0.201 vs. 1.434 +/- 0.134, P = 0.004). The level of variable
      region glycosylation of total IgG was significantly higher than that of affinity
      purified anti-GBM antibodies (1.034 +/- 0.340 vs. 0.734 +/- 0.333, P = 0.007).
      The SNA-binding fraction of MPO-ANCA-containing IgG and PR3-ANCA-containing IgG
      induced higher levels of neutrophil oxygen radical production than the
      corresponding non-SNA-binding fractions (P < 0.001 and P = 0.043, respectively).
      The level of variable region glycosylation of affinity-purified MPO-ANCA was
      higher in active AAV than the same patients in remission (P = 0.001). CONCLUSION:
      Characteristics of variable region glycosylation of ANCA and anti-GBM antibodies
      were different from that of total IgG, which might influence the antigen-binding
      ability of these antibodies. Variable region glycosylation of ANCA might
      influence the effect of ANCA-induced neutrophils respiratory burst.

PMID- 22404874
TI  - The 6-year attendance of a multidisciplinary prostate cancer clinic in Italy:
      incidence of management changes.
AB  - Study Type - Therapy (decision analysis) Level of Evidence 2b. What's known on
      the subject? and What does the study add? The benefits of the multidisciplinary
      approach in oncology are widely recognised. In particular, managing patients with
      prostate cancer within a multidisciplinarity and multiprofessional context is of
      paramount importance, to address the complexity of a disease where patients may
      be offered multiple therapeutic and observational options handled by different
      specialists and having severe therapy-induced side-effects. The present study
      describes the establishing of a multidisciplinary clinic at the Prostate Cancer
      Programme of Milan Istituto Nazionale dei Tumori, its effects on the quality of
      care provided, and strategies implemented to meet upcoming needs and improve
      quality standards. Having analysed the data of the 2260 multidisciplinary clinics
      held from March 2005 to March 2011, our dynamic and modifiable organisational
      model was evaluated for ways to optimise the human resources, offer high-quality
      standards, meet new needs and ultimately reduce costs. The study is focused on
      the organisational aspects and adds a perspective from one of the major
      oncological centres of reference in Italy and in Europe. OBJECTIVES: To describe
      the establishing of a multidisciplinary clinic for men with prostate cancer at
      the Istituto Nazionale Tumori, Milan. * To evaluate the quality of care provided
      and to describe the management changes implemented to improve standards and meet
      new needs. MATERIALS AND METHODS: In March 2005, we established a
      multidisciplinary clinic comprising weekly clinics and case-discussion sessions.
      * We have altered the organisational model periodically to meet new needs and
      improve quality. RESULTS: We held 2260 multidisciplinary clinics up to March
      2011. * For stage distribution, patients with low-risk prostate cancer increased
      to a peak of 61% in 2009, probably because of the anticipation of diagnosis and
      the active surveillance expertise of the Prostate Cancer Programme at Istituto
      Nazionale Tumori, Milan. The slight decrease in 2010 might be due to the
      availability of robot-assisted prostatectomy in several hospitals in Milan, and
      the start of a multicentre active surveillance protocol in December 2009. * In
      terms of the efficacy of our multidisciplinary strategy, 11% of drug therapies
      (mostly hormones) prescribed outside our institute were terminated in the
      multidisciplinary clinic, and 6% of indications formulated in the
      multidisciplinary clinics were altered during the case-discussion sessions.
      CONCLUSIONS: The multidisciplinary approach needs to be adaptable to meet new
      needs and improve quality. * Our experience has proved successful for both
      physicians and patients. The team agrees on strategies; complex cases are managed
      by a multidisciplinary team; dedicated psychologists contribute their knowledge
      and perspectives; and patients report the feeling of being cared for.

PMID- 22404875
TI  - Evaluating effects of normobaric oxygen therapy in acute stroke with MRI-based
      predictive models.
AB  - BACKGROUND: Voxel-based algorithms using acute multiparametric-MRI data have been
      shown to accurately predict tissue outcome after stroke. We explored the
      potential of MRI-based predictive algorithms to objectively assess the effects of
      normobaric oxygen therapy (NBO), an investigational stroke treatment, using data
      from a pilot study of NBO in acute stroke. METHODS: The pilot study of NBO
      enrolled 11 patients randomized to NBO administered for 8 hours, and 8 Control
      patients who received room-air. Serial MRIs were obtained at admission, during
      gas therapy, post-therapy, and pre-discharge. Diffusion/perfusion MRI data
      acquired at admission (pre-therapy) was used in generalized linear models to
      predict the risk of lesion growth at subsequent time points for both treatment
      scenarios: NBO or Control. RESULTS: Lesion volume sizes 'during NBO therapy'
      predicted by Control-models were significantly larger (P = 0.007) than those
      predicted by NBO models, suggesting that ischemic lesion growth is attenuated
      during NBO treatment. No significant difference was found between the predicted
      lesion volumes at later time-points. NBO-treated patients, despite showing larger
      lesion volumes on Control-models than NBO-models, tended to have reduced lesion
      growth. CONCLUSIONS: This study shows that NBO has therapeutic potential in acute
      ischemic stroke, and demonstrates the feasibility of using MRI-based algorithms
      to evaluate novel treatments in early-phase clinical trials.

PMID- 22404876
TI  - Survey context and question wording affects self reported annoyance due to road
      traffic noise: a comparison between two cross-sectional studies.
AB  - BACKGROUND: Surveys are a common way to measure annoyance due to road traffic
      noise, but the method has some draw-backs. Survey context, question wording and
      answer alternatives could affect participation and answers and could have
      implications when comparing studies and/or performing pooled analyses. The aim of
      this study was to investigate the difference in annoyance reporting due to road
      traffic noise in two types of surveys of which one was introduced broadly and the
      other with the clearly stated aim of investigating noise and health. METHODS:
      Data was collected from two surveys carried out in the municipality of Malmo,
      southern Sweden in 2007 and 2008 (n = 2612 and n = 3810). The first survey stated
      an aim of investigating residential environmental exposure, especially noise and
      health. The second survey was a broad public health survey stating a broader aim.
      The two surveys had comparable questions regarding noise annoyance, although one
      used a 5-point scale and the other a 4-point scale. We used geographic
      information systems (GIS) to assess the average road and railway noise (LAeq,24h)
      at the participants' residential address. Logistic regression was used to
      calculate odds ratios for annoyance in relation to noise exposure. RESULTS:
      Annoyance at least once a week due to road traffic noise was significantly more
      prevalent in the survey investigating environment and health compared to the
      public health survey at levels > 45 dB(A), but not at lower exposure levels.
      However no differences in annoyance were found when comparing the extreme
      alternatives "never" and "every day". In the study investigating environment and
      health, "Noise sensitive" persons were more likely to readily respond to the
      survey and were more annoyed by road traffic noise compared to the other
      participants in that survey. CONCLUSIONS: The differences in annoyance reporting
      between the two surveys were mainly due to different scales, suggesting that
      extreme alternatives are to prefer before dichotomization when comparing results
      between the two. Although some findings suggested that noise-sensitive
      individuals were more likely to respond to the survey investigating noise and
      health, we could not find convincing evidence that contextual differences
      affected either answers or participation.

PMID- 22404877
TI  - NAD(+) biosynthesis and salvage--a phylogenetic perspective.
AB  - NAD is best known as an electron carrier and a cosubstrate of various redox
      reactions. However, over the past 20 years, NAD(+) has been shown to be a key
      signaling molecule that mediates post-translational protein modifications and
      serves as precursor of ADP-ribose-containing messenger molecules, which are
      involved in calcium mobilization. In contrast to its role as a redox carrier,
      NAD(+)-dependent signaling processes involve the release of nicotinamide (Nam)
      and require constant replenishment of cellular NAD(+) pools. So far, very little
      is known about the evolution of NAD(P) synthesis in eukaryotes. In the present
      study, genes involved in NAD(P) metabolism in 45 species were identified and
      analyzed with regard to similarities and differences in NAD(P) synthesis. The
      results show that the Preiss-Handler pathway and NAD(+) kinase are present in all
      organisms investigated, and thus seem to be ancestral routes. Additionally, two
      pathways exist that convert Nam to NAD(+); we identified several species that
      have apparently functional copies of both biosynthetic routes, which have been
      thought to be mutually exclusive. Furthermore, our findings suggest the parallel
      phylogenetic appearance of Nam N-methyltransferase, Nam phosphoribosyl
      transferase, and poly-ADP-ribosyltransferases.

PMID- 22404878
TI  - Can computer-based assessment enhance the acceptance of formative multiple choice
      exams? A utility analysis.
AB  - BACKGROUND: Students' motivation to participate is one of the main challenges in
      formative assessment. The utility framework identifies potential points of
      intervention for improving the acceptance of formative assessment [Van Der
      Vleuten C. 1996. The assessment of professional competence: Developments,
      research and practical implications. Adv Health Sci Educ 1(1):41-67]. At the
      Medical Faculty of the University of Cologne, the paper-based version of the
      Berlin Progress Test has been transformed into computer-based version providing
      immediate feedback. AIM: To investigate whether the introduction of computer
      based assessment (CBA) enhances the acceptance of formative assessment relative
      to paper-based assessment (PBA). METHODS: In a retrospective cohort study (PBA: N
      = 2597, CBA: N = 2712), students' overall acceptance of the two forms of
      assessment was surveyed, their comments were analyzed, and we analyzed their test
      behavior and categorized students into "serious" or "non-serious" test takers.
      RESULTS: In the preclinical phase of medical education, no differences were found
      in overall acceptance of the two forms of assessment (p > 0.05). In the clinical
      phase, differences in favor of CBA were found in overall acceptance (p < 0.05),
      the proportion of positive comments (p < 0.001), and the proportion of serious
      participants (p < 0.001). CONCLUSIONS: Introduction of immediate feedback via CBA
      can enhance the acceptance and therefore the utility of formative assessment.

PMID- 22404879
TI  - Feasibility of mindfulness-based therapy in patients recovering from a first
      psychotic episode: a pilot study.
AB  - AIM: Recently, a mindfulness therapy for people with psychotic disorders was
      developed. However, clinicians and researchers are cautious given case reports in
      which extensive meditation provoked psychotic symptoms in people with a psychotic
      disorder. The purpose of this study was to examine the feasibility, adverse
      effects and possible favourable effects of mindfulness-based therapy (MBT) in
      people recently recovering from a first episode of psychosis. METHOD: A
      nonrandomized, non-controlled prospective follow-up study. Patients were offered
      an MBT that consisted of eight 1-hour sessions within a 4-week time span.
      Positive and Negative Syndrome Scale, Symptoms Checklist 90 and the Southampton
      Mindfulness Questionnaire were assessed before and after the therapy. RESULTS: Of
      the 16 persons who started MBT, 13 completed (81.5%) the therapy. No significant
      increase in psychotic symptoms was found. Between two meetings, one participant
      initially misunderstood the mindfulness instructions, which led to an increase in
      distress. No increased awareness of intrusive thoughts or visual or auditory
      hallucinations was reported by participants. We found a decrease in agoraphobic
      symptoms (p < 0.028) and in psychoneuroticism (P < 0.025). CONCLUSION: The MBT
      had no significant adverse effect on psychotic symptoms in patients in this small
      pilot study, neither did it raise the level of mindfulness in the participants. A
      decrease in psychological symptoms was found, although one patient experienced an
      increase in symptoms of distress. Our study demonstrates that therapists should
      be cautious that therapy and practice instructions are understood properly.
      Future studies are feasible and needed, in larger samples with an RCT design, in
      order to draw conclusions regarding the effects of the MBT.

PMID- 22404880
TI  - Epidemiology of classic and AIDS-related Kaposi's sarcoma in the USA: incidence,
      survival, and geographical distribution from 1975 to 2005.
AB  - This study aimed to examine trends in incidence, geographical distribution, and
      survival of classic and AIDS-related Kaposi's sarcoma (KS) in the general US
      population using Surveillance, Epidemiology, and End Results (SEER) tumour
      registries with 12 066 patients diagnosed with KS between 1975 and 2005. Although
      the age-adjusted standardized incidence ratio (SIR) of AIDS-related KS (1.9)
      during 1980-2005 was not significantly higher than that of classic KS (1.4)
      during 1975-2005 (P = 0.78), the trends in annual SIR rates revealed distinct
      patterns. While the SIR for AIDS-related KS declined across all registries from
      the early 1990s (4.6) to late-1990s (0.3) (P = 0.05), the SIR of classic KS
      remained relatively steady (1.7). In both forms the SIR of KS was highest in
      metropolitan areas. The 5-year survival rates for patients with AIDS-related KS
      improved from 12.1% (1980-1995) to 54% (1996-2005) (P = 0.05). Survival rates for
      patients with classic KS remained stable, ranging from 75.7% to 88.6% during the
      30-year period. These results may reflect improved HIV treatment.

PMID- 22404881
TI  - Towns with extremely low mortality due to ischemic heart disease in Spain.
AB  - BACKGROUND: The cause of coronary disease inframortality in Spain is unknown. The
      aim of this study is to identify Spanish towns with very low ischemic heart
      disease mortality, describe their health and social characteristics, and analyze
      the relationship with a series of contextual factors. METHODS: We obtained the
      number of deaths registered for each of 8,122 Spanish towns in the periods 1989
      1998 and 1999-2003. Expected deaths, standardized mortality ratio (SMR), smoothed
      Relative Risk (RR), and Posterior Probability (PP) of RR > 1 were calculated
      using Bayesian hierarchical models. Inframortality was defined as any town that
      displayed an RR below the 10th percentile, an SMR of under 1 for both sexes, and
      a PP of RR > 1 less than or equal to 0.002 for male and 0.005 for female
      mortality, during the two periods covered. All the remaining towns, except for
      those with high mortality classified as "tourist towns", were selected as
      controls. The association among socioeconomic, health, dietary, lifestyle and
      vascular risk factors was analyzed using sequential mixed logistic regression
      models, with province as the random-effects variable. RESULTS: We identified 32
      towns in which ischemic heart disease mortality was half the national rate and
      four times lower than the European Union rate, situated in lightly populated
      provinces spread across the northern half of Spain, and revealed a surprising
      pattern of geographic aggegation for 23 of the 32 towns. Variables related with
      inframortality were: a less aged population (OR 0.93, 95% CI 0.89-0.99); a
      contextual dietary pattern marked by a high fish content (OR 2.13, 95% CI 1.38
      3.28) and wine consumption (OR 1.50, 95% CI 1.08-2.07); and a low prevalence of
      obesity (OR 0.47, 95% CI 0.22-1.01); and, in the case of towns of over 1000
      inhabitants, a higher physician-population ratio (OR 3.80, 95% CI 1.17-12.3).
      CONCLUSIONS: Results indicate that dietary and health care factors have an
      influence on inframortality. The geographical aggregation suggests that other
      factors with a spatial pattern, e.g., genetic or environmental might also be
      implicated. These results will have to be confirmed by studies in situ, with
      objective measurements at an individual level.

PMID- 22404882
TI  - The marine cyanobacterium Crocosphaera watsonii WH8501 synthesizes the compatible
      solute trehalose by a laterally acquired OtsAB fusion protein.
AB  - Compatible solutes are small organic molecules that are involved in the
      acclimation to various stresses such as temperature and salinity. Marine or
      moderate halotolerant cyanobacteria accumulate glucosylglycerol, while
      cyanobacteria with low salt tolerance (freshwater strains) usually accumulate
      sucrose or trehalose as the main compatible solutes. The screening of the genome
      of the marine, unicellular N(2) -fixing cyanobacterium Crocosphaera watsonii
      WH8501 revealed that instead of genes for glucosylglycerol biosynthesis, a fusion
      protein for the synthesis of trehalose was found that displayed similarities to
      trehalose-phosphate-synthase and -phosphatase (OtsAB pathway) from
      enterobacteria. Accordingly, cells of Crocosphaera showed salt-stimulated
      expression of the otsAB gene as well as a salt-dependent trehalose accumulation.
      The biochemical characterization of recombinant full-length OtsAB and truncated
      OtsB versions revealed that the otsAB gene in Crocosphaera encodes for an active
      trehalose-phosphate-synthase/phosphatase fusion protein. Genes coding for such
      proteins were not found in the genomes of other cyanobacteria but were present in
      many other, non-related marine bacteria, suggesting that otsAB might have been
      acquired by lateral gene transfer into the Crocosphaera genome.

PMID- 22404883
TI  - Repeated short-term warming of red blood cell concentrates has minimal effect on
      their quality.
AB  - BACKGROUND AND OBJECTIVES: Blood components must be stored under controlled
      temperature conditions, for reasons of component quality and safety. However,
      there are occasions when components may be exposed to conditions outwith the
      defined limits. This study aimed to generate prospective data on the effect of
      red cell exposure to extremes of temperature. MATERIALS AND METHODS: Study 1: red
      cell concentrates (RCC) in saline, adenine, glucose and mannitol (SAGM), made
      after ambient overnight hold of whole blood, were exposed to either +22 degrees C
      or -2 degrees C for up to three periods of 3 h on days 3, 8 and 15 of storage,
      followed by a 5 h exposure on day 29. Study 2: RCC in SAGM were exposed to 25
      degrees C for 24 or 48 h from day 2. In vitro markers of cell quality were
      measured during storage to 43 days, and compared with control units that had been
      stored at 2-6 degrees C. RESULTS: Multiple short-term exposures to +22 degrees C
      or -2 degrees C did not cause any significant changes to pH, haemolysis,
      supernatant potassium, cellular ATP, 2,3-DPG, or deformability, when compared to
      control units. Exposure of RCC to 25 degrees C for 24 or 48 h caused a
      significant fall in pH, ATP, and deformability. CONCLUSION: Red cells may be
      damaged by prolonged exposure to warm temperatures, but repeated short-term
      exposure to 22 degrees C or -2 degrees C does not appear to affect the in vitro
      quality of RCC. It is important to note that no bacterial growth studies were
      performed during this study.

PMID- 22404884
TI  - Evidence-based neonatology--today and tomorrow.

PMID- 22404885
TI  - An evidence-based view on hyperbilirubinaemia.
AB  - INTRODUCTION: We conducted a review of the evidence which contributes to the
      current care of jaundiced newborn infants. METHODS: Literature was searched for
      reviews and randomized controlled trials (RCTs). RESULTS: Six Cochrane reviews
      and eight other reviews and eighteen recent RCTs are discussed. CONCLUSIONS: Many
      children still suffer life-long consequences of severe hyperbilirubinaemia, which
      could almost always have been prevented relatively easily. Up to date, guidelines
      summarizing the available evidence into unambiguous recommendations are needed to
      guide healthcare professionals in the prevention, diagnosis and treatment for
      infants with hyperbilirubinaemia.

PMID- 22404886
TI  - Evidence-based approach to preventing central line-associated bloodstream
      infection in the NICU.
AB  - AIM: To review care practices and methods of implementation that reduce the risk
      of central line-associated bloodstream infection (CLABSI). METHODS: Medical and
      quality improvement-oriented literature was reviewed. RESULTS: Although effective
      catheter practices, equipment and staff training methods are available to reduce
      CLABSI, their implementation is often difficult. CONCLUSION: A successful CLABSI
      reduction programme requires not only identification of best practices but also
      understanding of the specific context or unit culture into which they will be
      introduced.

PMID- 22404887
TI  - Inotropes in preterm infants--evidence for and against.
AB  - There is significant uncertainty regarding the optimal circulatory management of
      preterm infants, with research in the field limited by the paucity of safe,
      reproducible biomarkers of circulatory function. This review discusses the
      physiology and pathophysiology of circulatory function in preterm infants,
      describes the mode of action and evidence for and against commonly used and
      recently trialled inotropic therapies and provides recommendations for managing
      circulatory dysfunction in the transitional period and in the context of
      sepsis/necrotizing enterocolitis. We recommend a pragmatic approach of assessing
      multiple aspects of circulatory function (blood pressure alone correlates weakly
      with volume of flow) in each infant, tailoring therapy on the basis of the change
      in function desired and frequently reassessing response to intervention.

PMID- 22404888
TI  - RDS--CPAP or surfactant or both.
AB  - There is mounting evidence that early continuous positive airway pressure (CPAP)
      from birth is feasible and safe even in very preterm infants. However, many
      infants will develop respiratory distress syndrome (RDS) and require surfactant
      treatment. Combining a non-invasive ventilation approach with a strategy for
      surfactant administration is important, but questions remain about the optimal
      timing, mode of delivery and the value of predictive tests for surfactant
      deficiency. CONCLUSION: Early CPAP in very preterm infants is as safe as routine
      intubation in the delivery room. However, a strategy for surfactant
      administration should be part of a non-invasive ventilation approach for those
      infants at risk of developing significant RDS.

PMID- 22404889
TI  - Evidence for oxygen use in preterm infants.
AB  - AIM: To review the evidence for optimal oxygen use in preterm infants. RESULTS:
      Clinicians have embraced lower saturation targets to minimize retinopathy of
      prematurity (ROP). Large randomized trials now have shown that while such targets
      reduce ROP, neonatal mortality is increased significantly. CONCLUSIONS: Preterm
      infants should be resuscitated with blended oxygen (30-90%) targeted to avoid
      hyperoxia. Later, saturation management remains uncertain. Until ongoing trials
      and follow-up are complete, it is prudent to avoid saturation of 85-89%.

PMID- 22404890
TI  - Hyperoxia in the term newborn: more evidence is still needed for optimal oxygen
      therapy.
AB  - It took more than 30 years from the first observations that oxygen may be toxic
      during resuscitation till international guidelines changed to recommend that term
      and near term newborn infants should be resuscitated with air instead of 100%
      oxygen. There are still a number of unanswered questions related to oxygen
      therapy of the newborn infant. The newborn brain, lungs and other organs are
      susceptible to oxygen injury, and newborns still develop injury caused by
      hyperoxia.

PMID- 22404892
TI  - Branching structure and chain conformation of water-soluble glucan extracted from
      Auricularia auricula-judae.
AB  - A water-soluble neutral polysaccharide (AF1) was extracted from Auricularia (A.)
      auricula-judae with 0.15 M aqueous NaCl at 80-100  degrees C. Its chemical
      components and structure were analyzed by GC, GC-MS, and NMR. AF1 was identified
      as a beta-(1->3)-D-glucan with two beta-(1->6)-D-glucosyl residues for every
      three main chain glucose residues, showing a comb-branched structure. The M(w)
      values of AF1 in both aqueous solution and DMSO determined by LLS and SEC-LLS
      were in the narrow range of 2.07-2.15 * 10(6), indicating AF1 existed as single
      chains in the two solvents. The high intrinsic viscosity [eta] of 1753 mL/g and
      the structure-sensitive parameter rho (=R(g)/R(h)) value of 2.3 in water revealed
      that AF1 existed as stiff chain conformation. Moreover, we directly observed the
      extended stiff chain conformation by AFM. The branching structure led to the
      water solubility of AF1, and the intramolecular hydrogen bonds sustained the
      stiff chain conformation. The rheological results showed that this polysaccharide
      aqueous solution had higher viscosity than even xanthan, a pronounced thickening
      agent. This work provided important information for developing new thickeners in
      food fields, and how neutral polysaccharides can be used as good candidates.

PMID- 22404891
TI  - Oxidative lipid modification of nicastrin enhances amyloidogenic gamma-secretase
      activity in Alzheimer's disease.
AB  - The cause of elevated level of amyloid beta-peptide (Abeta42) in common late
      onset sporadic [Alzheimer's disease (AD)] has not been established. Here, we show
      that the membrane lipid peroxidation product 4-hydroxynonenal (HNE) is associated
      with amyloid and neurodegenerative pathologies in AD and that it enhances gamma
      secretase activity and Abeta42 production in neurons. The gamma-secretase
      substrate receptor, nicastrin, was found to be modified by HNE in cultured
      neurons and in brain specimens from patients with AD, in which HNE-nicastrin
      levels were found to be correlated with increased gamma-secretase activity and
      Abeta plaque burden. Furthermore, HNE modification of nicastrin enhanced its
      binding to the gamma-secretase substrate, amyloid precursor protein (APP) C99. In
      addition, the stimulation of gamma-secretase activity and Abeta42 production by
      HNE were blocked by an HNE-scavenging histidine analog in a 3xTgAD mouse model of
      AD. These findings suggest a specific molecular mechanism by which oxidative
      stress increases Abeta42 production in AD and identify HNE as a novel therapeutic
      target upstream of the gamma-secretase cleavage of APP.

PMID- 22404894
TI  - Multifocal PEComa (PEComatosis) of the female genital tract and pelvis: a case
      report and review of the literature.
AB  - Perivascular epithelioid cells (PECs) are constantly present in a group of tumors
      called PEComas, including angiomyolipoma (AML), clear-cell "sugar" tumor (CCST)
      of the lung and extrapulmonary sites, lymphangioleiomyomatosis, clear-cell
      myomelanocytic tumor of the falciform ligament/ligamentum teres and rare clear
      cell tumors of other anatomic sites. PECs have distinctive morphologic,
      immunohistochemical, ultrastructural and genetic characteristics, including an
      epithelioid appearance with a clear to granular cytoplasm, a round to oval,
      centrally located nucleus, and an inconspicuous nucleolus. PECs also express
      melanocytic and myogenic markers like HMB45 and smooth muscle actin. PEComa is
      rare in human, and multifocal PEComas (PEComatosis) is extremely rare. Up to now
      there have been only less than 5 cases described in the literature. Here we
      report a 46-year old Chinese woman who had PEComatosis arising from the genital
      tract and pelvis. To our knowledge, this is the first case of PEComatosis ever
      reported in China. VIRTUAL SLIDES: The virtual slide(s) for this article can be
      found here: http://www.diagnosticpathology.diagnomx.eu/vs/1293097548652023.

PMID- 22404893
TI  - Increased levels of prolactin receptor expression correlate with the early onset
      of lupus symptoms and increased numbers of transitional-1 B cells after prolactin
      treatment.
AB  - BACKGROUND: Prolactin is secreted from the pituitary gland and other organs, as
      well as by cells such as lymphocytes. Prolactin has an immunostimulatory effect
      and is associated with autoimmune diseases that are characterised by abnormal B
      cell activation, such as systemic lupus erythematosus (SLE). Our aim was to
      determine if different splenic B cell subsets express the prolactin receptor and
      if the presence of prolactin influences these B cell subsets and correlates with
      development of lupus. RESULTS: Using real-time PCR and flow cytometry, we found
      that different subsets of immature (transitional) and mature (follicular,
      marginal zone) B cells express different levels of the prolactin receptor and are
      differentially affected by hyperprolactinaemia. We found that transitional B
      cells express the prolactin receptor at higher levels compared to mature B cells
      in C57BL/6 mice and the lupus-prone MRL/lpr and MRL mouse strains. Transitional-1
      (T1) B cells showed a higher level of prolactin receptor expression in both
      MRL/lpr and MRL mice compared to C57BL/6 mice. Hyperprolactinaemia was induced
      using metoclopramide, which resulted in the development of early symptoms of SLE.
      We found that T1 B cells are the main targets of prolactin and that prolactin
      augments the absolute number of T1 B cells, which reflects the finding that this
      B cell subpopulation expresses the highest level of the prolactin receptor.
      CONCLUSIONS: We found that all B cell subsets express the prolactin receptor but
      that transitional B cells showed the highest prolactin receptor expression
      levels. Hyperprolactinaemia in mice susceptible to lupus accelerated the disease
      and increased the absolute numbers of T1 and T3 B cells but not of mature B
      cells, suggesting a primary effect of prolactin on the early stages of B cell
      maturation in the spleen and a role of prolactin in B cell differentiation,
      contributing to SLE onset.

PMID- 22404895
TI  - Effects of rigid and non-rigid image registration on test-retest variability of
      quantitative [18F]FDG PET/CT studies.
AB  - BACKGROUND: [18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography
      (PET) is a valuable tool for monitoring response to therapy in oncology. In
      longitudinal studies, however, patients are not scanned in exactly the same
      position. Rigid and non-rigid image registration can be applied in order to reuse
      baseline volumes of interest (VOI) on consecutive studies of the same patient.
      The purpose of this study was to investigate the impact of various image
      registration strategies on standardized uptake value (SUV) and metabolic volume
      test-retest variability (TRT). METHODS: Test-retest whole-body [18F]FDG PET/CT
      scans were collected retrospectively for 11 subjects with advanced
      gastrointestinal malignancies (colorectal carcinoma). Rigid and non-rigid image
      registration techniques with various degrees of locality were applied to PET, CT,
      and non-attenuation corrected PET (NAC) data. VOI were drawn independently on
      both test and retest scans. VOI drawn on test scans were projected onto retest
      scans and the overlap between projected VOI and manually drawn retest VOI was
      quantified using the Dice similarity coefficient (DSC). In addition, absolute
      (unsigned) differences in TRT of SUVmax, SUVmean, metabolic volume and total
      lesion glycolysis (TLG) were calculated in on one hand the test VOI and on the
      other hand the retest VOI and projected VOI. Reference values were obtained by
      delineating VOIs on both scans separately. RESULTS: Non-rigid PET registration
      showed the best performance (median DSC: 0.82, other methods: 0.71-0.81).
      Compared with the reference, none of the registration types showed significant
      absolute differences in TRT of SUVmax, SUVmean and TLG (p > 0.05). Only for
      absolute TRT of metabolic volume, significant lower values (p < 0.05) were
      observed for all registration strategies when compared to delineating VOIs
      separately, except for non-rigid PET registrations (p = 0.1). Non-rigid PET
      registration provided good volume TRT (7.7%) that was smaller than the reference
      (16%). CONCLUSION: In particular, non-rigid PET image registration showed good
      performance similar to delineating VOI on both scans separately, and with smaller
      TRT in metabolic volume estimates.

PMID- 22404896
TI  - [Medicolegal analysis of legal claims in bariatric surgery].
AB  - OBJECTIVES: To analyse the causes for claims due to alleged malpractice in
      bariatric surgery and the results of the legal process. MATERIAL AND METHOD: A
      review was carried out on the case files of claims for damages as a result of
      bariatric surgery presented to the Professional Liability Department of the
      Catalonian Medical Colleges Council from 1992 to 2009. The claims rate was
      calculated using a survey of bariatric surgeons. RESULTS: A total of 49 cases
      were analysed, which represented 0.6% of the patients operated on. The patient
      died in 23 (47%) of the cases, 14% were left with serious after effects, 18% had
      mild after effects, and 21% made a complete recovery. The most frequent causes of
      death were peritonitis due to suture dehiscence (48%), and respiratory
      complications (17.4%). Retrospectively, malpractice was considered to have
      occurred in 10 (20%) of the sued cases due to lack of an adequate informed
      consent document, delay in recognising a complication, or an error in
      interpretation, or treatment of the complication. The doctor sued was convicted
      in 10 of the cases, 3 in a criminal court, and 7 in a civil court. There was
      acquittal in 19 cases, an out-of court settlement with payment of compensation in
      4, withdrawal of the claim in 4, and judgement or sentence is still pending in 12
      cases. CONCLUSION: The study showed a relatively low rate of claims for
      complications associated with bariatric surgery. The number of convictions was
      relatively high. The early detection of surgical complications is essential in
      order to reduce legal claims associated with bariatric surgery.

PMID- 22404897
TI  - [Laparoscopic fundoplication results in the treatment of the non-gastrointestinal
      symptoms of gastroesophageal reflux].
AB  - INTRODUCTION: Gastroesophageal reflux disease (GERD) can trigger typical and
      atypical symptoms (cough, dysphonia, asthma...). GERD with typical symptoms has
      well established surgical indications, but it is not the case when the symptoms
      are atypical. Our aim is to assess the effectiveness of laparoscopic surgery in
      those patients in whom the surgical indication was mainly due to atypical
      symptoms. MATERIAL AND METHODS: Between 1998 and 2011 laparoscopic fundoplication
      was performed on of 318 patients with GERD, of whom 14 (4%) had atypical symptoms
      as the main indication. Typical symptoms were present in 12 (86%) cases, and
      atypical symptoms were: cough in 5 (36%) cases, respiratory symptoms 5 (36%),
      dysphonia 2 (14%), vocal chords granuloma 1 (7%) and larynx spasm 1 (7%). The
      GERD diagnosis was established due to evidence of an anatomical or functional
      alterations of the gastroesophageal junction (hiatus hernia, pathological
      manometry or pH-metry). The clinical histories of the patients were reviewed and
      they were given a gastrointestinal quality of life (Gastrointestinal Quality of
      Life Index [GIQoL]) questionnaire was completed, as well as a subjective
      assessment (0 to 4) of the modification of their atypical symptoms. RESULTS: A
      clinical improvement was observed in both the atypical and typical GERD in 12
      patients (86%), with the symptoms score decreasing from 3.7 to 0.7. A significant
      improvement (P<.05) from the pre-surgical value 107(+/-26) to 122 (+/-10) points
      was obtained in the quality of life (GIQoL) in 11 patients (79%). CONCLUSION:
      Laparoscopic fundoplication is an effective technique in the treatment of the
      atypical symptoms of GERD.

PMID- 22404898
TI  - Impact of surgeon experience on complication rates and functional outcomes of 484
      deceased donor renal transplants: a single-centre retrospective study.
AB  - OBJECTIVE: To determine how postoperative and functional outcomes after deceased
      donor renal transplantation (DDRT) are related to surgeon experience. PATIENTS
      AND METHODS: The outcomes of 484 adult DDRT performed by 13 urological surgeons
      were retrospectively reviewed. After completion of a staged renal transplant
      training programme under supervision of an attending urological transplant
      surgeon, the 13 surgeons were either assigned to the inexperienced group (n = 8)
      or the experienced group (n = 5). Surgeons in the experienced group had performed
      more than 30 unsupervised DDRT in a standard fashion with routine ureteric
      stenting. Between 1988 and 2005, inexperienced surgeons performed 152 DDRT,
      whereas experienced surgeons performed 332 DDRT. RESULTS: Patient and graft
      survival at 2 hyears were 98% and 94.7%, respectively. Early graft loss in five
      recipients was unrelated to surgeon experience. Delayed graft function occurred
      in 29% of cases and median 1-year serum-creatinine was 1.48 mg/dL, with no
      difference between surgeon groups. Postoperative bleeding and lymphocele
      formation were the most frequent surgical complications, with an equal
      distribution between groups. Ureteric complications had a significantly higher
      incidence among inexperienced surgeons (6.6% versus 2.7%; P = 0.04). CONCLUSION:
      We conclude that DDRT as performed by inexperienced urological renal transplant
      surgeons has both acceptable short- and long-term outcomes.

PMID- 22404899
TI  - Evolutionary and physical linkage between calpains and penta-EF-hand Ca2+-binding
      proteins.
AB  - The name calpain was historically given to a protease that is activated by Ca(2+)
      and whose primary structure contains a Ca(2+)-binding penta-EF-hand (PEF) as well
      as a calpain cysteine protease (CysPc) domain and a C2-domain-like (C2L) domain.
      In the human genome, CysPc domains are found in 15 genes, but only nine of them
      encode PEF domains. Fungi and budding yeasts have calpain-like sequences that
      lack the PEF domain, and each protein (designated PalB and Rim13, respectively)
      is orthologous to human calpain-7, indicating that the calpain-7 orthologs are
      evolutionarily more conserved than classical calpains possessing PEF domains. An
      N-terminal region of calpain-7 has a tandem repeat of microtubule-interacting and
      transport domains that interact with a subset of endosomal sorting complex
      required for transport (ESCRT) III proteins. In addition to calpains, PEF domains
      are found in other Ca(2+)-binding proteins including ALG-2 that associates with
      ALIX (an ESCRT-III accessory protein) and TSG101 (an ESCRT-I subunit).
      Phylogenetic comparison of dissected domain structures of calpains and
      experimentally confirmed protein-protein interaction networks imply that there is
      an evolutionary and physical linkage between mammalian calpains and PEF proteins
      involving the ESCRT system.

PMID- 22404900
TI  - Successful salvage therapy with Daptomycin for osteomyelitis caused by
      methicillin-resistant Staphylococcus aureus in a renal transplant recipient with
      Fabry-Anderson disease.
AB  - Daptomycin is licensed in adults for the management of Staphylococcus aureus
      methicillin-resistant infections, including bone and skin complicated infections.
      We describe for the first time its use in a renal transplant recipient for Fabry
      Anderson Disease with right heel osteomyelitis. The patient was unresponsive to
      first-line Teicoplanin and second-line Tigecycline, whereas he was successfully
      treated with third-line Daptomycin monotherapy at 4 mg/Kg/qd for 4 weeks. Local
      debridement was performed in advance of each line of treatment.

PMID- 22404901
TI  - Health claims assessment in the field of joint and cartilage: a consensus
      viewpoint of the Group for the Respect of Ethics and Excellence in Science.
AB  - INTRODUCTION: In 2006, the European Parliament and Council issued a regulation
      (No. 1924/2006) for the nutrition and health claims made on foods, including food
      supplements. According to the regulation, the use of nutrition and health claims
      shall only be permitted if the substance in respect of which the claim is made
      has been shown to have a beneficial nutritional or physiological effect. In the
      field of joint and cartilage health, there is no clear scientific-based
      definition of the nature of such a beneficial nutritional or physiological
      effect. The objective of this paper is to scientifically define the possible
      content of health claims related to joint and cartilage health and to provide
      scientific guidelines for the design of clinical studies which need to be adopted
      to substantiate such health claims. METHODS: Literature review up to September
      2011 followed by a consensus expert discussion organized by the Group for the
      Respect of Ethics and Excellence in Science (GREES). RESULTS: In line with the
      general principles of the PASSCLAIM and the Codex recommendations, the GREES
      identified four acceptable health claims related to joint and cartilage health
      based on the effects on discomfort, joint and cartilage structural integrity or
      risk factors for joint and cartilage diseases. The GREES considers that
      randomized controlled trials on a relevant outcome is the best design to assess
      health claims. Moreover, animal studies could also be of interest to substantiate
      some health claims, to assess the clinical relevance of endpoints used in human
      studies or to extrapolate data obtained in patients to the target (apparently)
      healthy population. CONCLUSION: According to the methodology and biomarkers used
      in the study and whether or not additional animal studies are provided to support
      the claim, various health claims can be acceptable in the field of joint and
      cartilage health.

PMID- 22404902
TI  - Evidence for high-temperature in situ nifH transcription in an alkaline hot
      spring of Lower Geyser Basin, Yellowstone National Park.
AB  - Genes encoding nitrogenase (nifH) were amplified from sediment and photosynthetic
      mat samples collected in the outflow channel of Mound Spring, an alkaline thermal
      feature in Yellowstone National Park. Results indicate the genetic capacity for
      nitrogen fixation over the entire range of temperatures sampled (57.2 degrees C
      to 80.2 degrees C). Amplification of environmental nifH transcripts revealed in
      situ expression of nifH genes at temperatures up to 72.7 degrees C. However, we
      were unable to amplify transcripts of nifH at the higher-temperature locations (>
      72.7 degrees C). These results indicate that microbes at the highest temperature
      sites contain the genetic capacity to fix nitrogen, yet either do not express
      nifH or do so only transiently. Field measurements of nitrate and ammonium show
      fixed nitrogen limitation as temperature decreases along the outflow channel,
      suggesting nifH expression in response to the downstream decrease in bioavailable
      nitrogen. Nitrogen stable isotope values of Mound Spring sediment communities
      further support geochemical and genetic data. DNA and cDNA nifH amplicons form
      several unique phylogenetic clades, some of which appear to represent novel nifH
      sequences in both photosynthetic and chemosynthetic microbial communities. This
      is the first report of in situ nifH expression in strictly chemosynthetic zones
      of terrestrial (non-marine) hydrothermal systems, and sets a new upper
      temperature limit (72.7 degrees C) for nitrogen fixation in alkaline, terrestrial
      hydrothermal environments.

PMID- 22404903
TI  - Woman-centered research on access to safe abortion services and implications for
      behavioral change communication interventions: a cross-sectional study of women
      in Bihar and Jharkhand, India.
AB  - BACKGROUND: Unsafe abortion in India leads to significant morbidity and
      mortality. Abortion has been legal in India since 1971, and the availability of
      safe abortion services has increased. However, service availability has not led
      to a significant reduction in unsafe abortion. This study aimed to understand the
      gap between safe abortion availability and use of services in Bihar and
      Jharkhand, India by examining accessibility from the perspective of rural, Indian
      women. METHODS: Two-stage stratified random sampling was used to identify and
      enroll 1411 married women of reproductive age in four rural districts in Bihar
      and Jharkhand, India. Data were collected on women's socio-demographic
      characteristics; exposure to mass media and other information sources; and
      abortion-related knowledge, perceptions and practices. Multiple linear regression
      models were used to explore the association between knowledge and perceptions
      about abortion. RESULTS: Most women were poor, had never attended school, and had
      limited exposure to mass media. Instead, they relied on community health workers,
      family and friends for health information. Women who had knowledge about
      abortion, such as knowing an abortion method, were more likely to perceive that
      services are available (beta = 0.079; p < 0.05) and have positive attitudes
      toward abortion (beta = 0.070; p < 0.05). In addition, women who reported
      exposure to abortion messages were more likely to have favorable attitudes toward
      abortion (beta = 0.182; p < 0.05). CONCLUSIONS: Behavior change communication
      (BCC) interventions, which address negative perceptions by improving community
      knowledge about abortion and support local availability of safe abortion
      services, are needed to increase enabling resources for women and improve
      potential access to services. Implementing BCC interventions is challenging in
      settings such as Bihar and Jharkhand where women may be difficult to reach
      directly, but interventions can target individuals in the community to transfer
      information to the women who need this information most. Interpersonal approaches
      that engage community leaders and influencers may also counteract negative social
      norms regarding abortion and associated stigma. Collaborative actions of
      government, NGOs and private partners should capitalize on this potential power
      of communities to reduce the impact of unsafe abortion on rural women.

PMID- 22404904
TI  - Induction of the plasticity-associated immediate early gene Arc by stress and
      hallucinogens: role of brain-derived neurotrophic factor.
AB  - Exposure to stress and hallucinogens in adulthood evokes persistent alterations
      in neurocircuitry and emotional behaviour. The structural and functional changes
      induced by stress and hallucinogen exposure are thought to involve
      transcriptional alterations in specific effector immediate early genes. The
      immediate early gene, activity regulated cytoskeletal-associated protein (Arc),
      is important for both activity and experience dependent plasticity. We sought to
      examine whether trophic factor signalling through brain-derived neurotrophic
      factor (BDNF) contributes to the neocortical regulation of Arc mRNA in response
      to distinct stimuli such as immobilization stress and the hallucinogen 2,5
      dimethoxy-4-iodoamphetamine (DOI). Acute exposure to either immobilization stress
      or DOI induced Arc mRNA levels within the neocortex. BDNF infusion into the
      neocortex led to a robust up-regulation of local Arc transcript expression.
      Further, baseline Arc mRNA expression in the neocortex was significantly
      decreased in inducible BDNF knockout mice with an adult-onset, forebrain specific
      BDNF loss. The induction of Arc mRNA levels in response to both acute
      immobilization stress or a single administration of DOI was significantly
      attenuated in the inducible BDNF knockout mice. Taken together, our results
      implicate trophic factor signalling through BDNF in the regulation of cortical
      Arc mRNA expression, both under baseline conditions and following stress and
      hallucinogen exposure. These findings suggest the possibility that the regulation
      of Arc expression via BDNF provides a molecular substrate for the structural and
      synaptic plasticity observed following stimuli such as stress and hallucinogens.

PMID- 22404906
TI  - Acute and chronic hypoxia: breathe, breathe in the air.

PMID- 22404905
TI  - Glucocorticoids suppress selected components of the senescence-associated
      secretory phenotype.
AB  - Cellular senescence suppresses cancer by arresting the proliferation of cells at
      risk for malignant transformation. Recently, senescent cells were shown to
      secrete numerous cytokines, growth factors, and proteases that can alter the
      tissue microenvironment and may promote age-related pathology. To identify small
      molecules that suppress the senescence-associated secretory phenotype (SASP), we
      developed a screening protocol using normal human fibroblasts and a library of
      compounds that are approved for human use. Among the promising library
      constituents was the glucocorticoid corticosterone. Both corticosterone and the
      related glucocorticoid cortisol decreased the production and secretion of
      selected SASP components, including several pro-inflammatory cytokines.
      Importantly, the glucocorticoids suppressed the SASP without reverting the tumor
      suppressive growth arrest and were efficacious whether cells were induced to
      senesce by ionizing radiation or strong mitogenic signals delivered by oncogenic
      RAS or MAP kinase kinase 6 overexpression. Suppression of the prototypical SASP
      component IL-6 required the glucocorticoid receptor, which, in the presence of
      ligand, inhibited IL-1alpha signaling and NF-kappaB transactivation activity.
      Accordingly, co-treatments combining glucocorticoids with the glucocorticoid
      antagonist RU-486 or recombinant IL-1alpha efficiently reestablished NF-kappaB
      transcriptional activity and IL-6 secretion. Our findings demonstrate feasibility
      of screening for compounds that inhibit the effects of senescent cells. They
      further show that glucocorticoids inhibit selected components of the SASP and
      suggest that corticosterone and cortisol, two FDA-approved drugs, might exert
      their effects in part by suppressing senescence-associated inflammation.

PMID- 22404907
TI  - Distribution of hepatitis C virus in circulating blood components from blood
      donors.
AB  - BACKGROUND AND OBJECTIVES: Current nucleic acid tests (NAT) for blood donor
      screening use plasma as the test sample and, consequently, cannot detect virions
      bound to blood cells of infected donors. Hepatitis C virus (HCV) RNA and
      infectious virions have been detected in association with the cellular components
      of blood of patients with active liver disease; however, studies comparing HCV
      viral loads in whole blood and plasma have generated contradictory results. The
      aim of this study was to investigate the distribution of HCV in different
      compartments of the peripheral blood from HCV-infected blood donors, which may
      differ from that observed in patients with HCV-associated liver disease.
      MATERIALS AND METHODS: Hepatitis C virus-positive donor specimens were identified
      by NAT and antibody testing. HCV RNA was extracted from samples of whole blood
      and their corresponding components (RBC and plasma). Viral RNA was quantified by
      real-time qRT-PCR. RESULTS: Hepatitis C virus was present in all blood components
      from infected donors from which RNA could be amplified. For the majority of
      samples, plasma (34/46) had the highest detectable concentration of HCV RNA, and
      RBC (37/46) had the lowest. Specimens with negative NAT and positive antibody
      assays also produced qRT-PCR negative results. CONCLUSION: These results indicate
      that including the RBC fraction in the tested sample will not increase assay
      sensitivity. Although 10% of the specimens had a higher viral load in whole
      blood, there was no significant overall increase in sensitivity to justify
      changes in the specimen format. Thus, plasma specimens are well suited for blood
      donor screening for HCV.

PMID- 22404908
TI  - Effect of cancer-associated mutations in the PlexinB1 gene.
AB  - BACKGROUND: Semaphorins act as chemotactic cues for cell movement via their
      transmembrane receptors, plexins. Somatic missense mutations in the plexinB1 gene
      coupled with overexpression of the protein frequently occur in prostate tumours,
      indicating a role for plexinB1 in the pathogenesis of prostate cancer. RESULTS:
      Two specific mutations found in prostate cancer enhance RhoD binding and one
      other mutation results in loss of inhibition of Rac-dependent Pak1
      phosphorylation and lamellipodia formation and in impairment of trafficking of
      plexinB1 to the membrane. None of the three characterised mutations affect
      PDZRhoGEF binding, RhoA activity, the interaction of plexinB1 with the oncogenes
      ErbB2 or c-Met or ErbB2 phosphorylation. The mutations have the net effect of
      increasing cell motility by blocking plexinB1-mediated inhibition of Rac while
      enhancing the interaction with RhoD, an anti-migratory factor. CONCLUSIONS:
      PlexinB1 mutations block plexinB1-mediated signalling pathways that inhibit cell
      motility.

PMID- 22404909
TI  - Molecular probe technology detects bacteria without culture.
AB  - BACKGROUND: Our ultimate goal is to detect the entire human microbiome, in health
      and in disease, in a single reaction tube, and employing only commercially
      available reagents. To that end, we adapted molecular inversion probes to detect
      bacteria using solely a massively multiplex molecular technology. This molecular
      probe technology does not require growth of the bacteria in culture. Rather, the
      molecular probe technology requires only a sequence of forty sequential bases
      unique to the genome of the bacterium of interest. In this communication, we
      report the first results of employing our molecular probes to detect bacteria in
      clinical samples. RESULTS: While the assay on Affymetrix GenFlex Tag16K arrays
      allows the multiplexing of the detection of the bacteria in each clinical sample,
      one Affymetrix GenFlex Tag16K array must be used for each clinical sample. To
      multiplex the clinical samples, we introduce a second, independent assay for the
      molecular probes employing Sequencing by Oligonucleotide Ligation and Detection.
      By adding one unique oligonucleotide barcode for each clinical sample, we combine
      the samples after processing, but before sequencing, and sequence them together.
      CONCLUSIONS: Overall, we have employed 192 molecular probes representing 40
      bacteria to detect the bacteria in twenty-one vaginal swabs as assessed by the
      Affymetrix GenFlex Tag16K assay and fourteen of those by the Sequencing by
      Oligonucleotide Ligation and Detection assay. The correlations among the assays
      were excellent.

PMID- 22404910
TI  - The BRIC-GARN Meeting 2011: of mice and men.

PMID- 22404911
TI  - Keeping participants on board: increasing uptake by automated respondent
      reminders in an Internet-based chlamydia screening in the Netherlands.
AB  - BACKGROUND: Effectiveness of Chlamydia screening programs is determined by an
      adequate level of participation and the capturing of high-risk groups. This study
      aimed to evaluate the contribution of automated reminders by letter, email and
      short message service (SMS) on package request and sample return in an Internet
      based Chlamydia screening among people aged 16 to 29 years in the Netherlands.
      METHODS: Individuals not responding to the invitation letter received a reminder
      letter after 1 month. Email- and SMS-reminders were sent to persons who did not
      return their sample. It was examined to what extent reminders enhanced the
      response rate (% of package requests) and participation rate (% of sample
      return). Sociodemographic and behavioural correlates of providing a cell phone
      number and participation after the reminder(s) were studied by logistic
      regression models. RESULTS: Of all respondents (screening round 1: 52,628, round
      2: 41,729), 99% provided an email address and 72% a cell phone number. Forty-two
      percent of all package requests were made after the reminder letter. The
      proportion of invitees returning a sample increased significantly from 10% to 14%
      after email/SMS reminders (round 2: from 7% to 10%). Determinants of providing a
      cell-phone number were younger age (OR in 25-29 year olds versus 16-19 year olds
      = 0.8, 95%CI 0.8-0.9), non-Dutch (OR in Surinam/Antillean versus Dutch = 1.3,
      95%CI 1.2-1.4, Turkish/Moroccan: 1.1, 95%CI 1.0-1.2, Sub Sahara African: 1.5,
      95%CI 1.3-1.8, non-Western other 1.1, 95%CI 1.1-1.2), lower educational level (OR
      in high educational level versus low level = 0.8, 95%CI 0.7-0.9), no condom use
      during the last contact with a casual partner (OR no condom use versus condom use
      1.2, 95%CI 1.1-1.3), younger age at first sexual contact (OR 19 years or older
      versus younger than 16: 0.7, 95%CI 0.6-0.8). Determinants for requesting a test
      package after the reminder letter were male gender (OR female versus male 0.9
      95%CI 0.8-0.9), non-Dutch (OR in Surinam/Antillean versus Dutch 1.3, 95%CI 1.2
      1.4, Turkish/Moroccan: 1.4, 95%CI 1.3-1.5, Sub Sahara African: 1.4, 95%CI 1.2
      1.5, non-Western other: 1.2, 95%CI 1.1-1.2), having a long-term steady
      partnership (long-term versus short-term.1.2 95%CI 1.1-1.3). Email/SMS reminders
      seem to have resulted in more men and people aged 25-29 years returning a sample.
      CONCLUSIONS: Nearly all respondents (99.5%) were reachable by modern
      communication media. Response and participation rates increased significantly
      after the reminders. The reminder letters also seemed to result in reaching more
      people at risk. Incorporation of automated reminders in Internet-based
      (Chlamydia) screening programs is strongly recommended.

PMID- 22404912
TI  - An unusual accessory mandible and a submucosal cleft palate-a case report and
      review of the literature.
AB  - An accessory mandible is a rare congenital anomaly that requires
      multidisciplinary management. This case report describes a female patient with an
      unusual accessory mandible, a dysplastic overgrowth of bone, containing teeth
      that extended from the midsymphyseal region. A submucosal cleft palate and cleft
      of the lower lip were also present. Her treatment plan took a staged approach
      with initial surgical resection of the accessory bone and teeth. The second
      stage, still in the planning phase, will correct the secondary deformity of an
      anterior open bite and will restore the missing lower anterior teeth. The
      original deformity and subsequent growth are discussed with the relevant
      literature.

PMID- 22404913
TI  - ESCRT and calpain--old and new relationships.
AB  - Apparently unrelated systems often merge and work together to achieve diverse
      biological functions. This minireview series was aimed to unveil new facets of
      ESCRTs and calpains: ESCRT proteins in MVB formation, virus budding and cell
      division; the ambient pH sensing and adaptation in association with ESCRTs and
      the calpain system; evolutionary and physical linkage between calpains and PEF
      proteins.

PMID- 22404914
TI  - Integrated metagenomic and metaproteomic analyses of an ANME-1-dominated
      community in marine cold seep sediments.
AB  - Sulfate-reducing methanotrophy by anaerobic methanotrophic archaea (ANME) and
      sulfate-reducing bacteria (SRB) is a major biological sink of methane in anoxic
      methane-enriched marine sediments. The physiology of a microbial community
      dominated by free-living ANME-1 at 14-16 cm below the seafloor in the G11
      pockmark at Nyegga was investigated by integrated metagenomic and metaproteomic
      approaches. Total DNA was subjected to 454-pyrosequencing (829 527 reads), and
      16.6 Mbp of sequence information was assembled into 27352 contigs. Taxonomic
      analysis supported a high abundance of Euryarchaea (70%) with 66% of the
      assembled metagenome belonging to ANME-1. Extracted sediment proteins were
      separated in two dimensions and subjected to mass spectrometry (LTQ-Orbitrap XL).
      Of 356 identified proteins, 245 were expressed by ANME-1. These included proteins
      for cold-adaptation and production of gas vesicles, reflecting both the
      adaptation of the ANME-1 community to a permanently cold environment and its
      potential for positioning in specific sediment depths respectively. In addition,
      key metabolic enzymes including the enzymes in the reverse methanogenesis pathway
      (except N(5) ,N(10) -methylene-tetrahydromethanopterin reductase),
      heterodisulfide reductases and the F(420) H(2) :quinone oxidoreductase (Fqo)
      complex were identified. A complete dissimilatory sulfate reduction pathway was
      expressed by sulfate-reducing Deltaproteobacteria. Interestingly, an APS
      reductase comprising Gram-positive SRB and related sequences were identified in
      the proteome. Overall, the results demonstrated that our approach was effective
      in assessing in situ metabolic processes in cold seep sediments.

PMID- 22404915
TI  - A novel procedure for absolute real-time quantification of gene expression
      patterns.
AB  - BACKGROUND: Temporal and tissue-specific patterns of gene expression play
      important roles in functionality of a biological system. Real-time quantitative
      polymerase chain reaction (qPCR) technique has been widely applied to single gene
      expressions, but its potential has not been fully released as most results have
      been obtained as fold changes relative to control conditions. Absolute
      quantification of transcripts as an alternative method has yet to gain popularity
      because of unresolved issues. RESULTS: We propose a solution here with a novel
      procedure, which may accurately quantify the total cDNA conventionally prepared
      from a biological sample at the resolution of ~70 pg/MUl, and reliably estimate
      the absolute numbers of transcripts in a picogram of cDNA. In comparison to the
      relative quantification, cDNA-based absolute (CBA) qPCR method is found to be
      more sensitive to gene expression variations caused by factors such as
      developmental and environmental variations. If the number of target transcript
      copies is further normalized by reference transcripts, cell-level variation
      pattern of the target gene expression may also be detectable during a
      developmental process, as observed here in cases across species (Ipomoea
      purpurea, Nicotiana benthamiana) and tissues (petals and leaves). CONCLUSION: By
      allowing direct comparisons of results across experiments, the new procedure
      opens a window to make inferences of gene expression patterns across a broad
      spectrum of living systems and tissues. Such comparisons are urgently needed for
      biological interpretations of gene expression variations in diverse cells.

PMID- 22404916
TI  - Snake-venom resistance as a mammalian trophic adaptation: lessons from didelphid
      marsupials.
AB  - Mammals that prey on venomous snakes include several opossums (Didelphidae), at
      least two hedgehogs (Erinaceidae), several mongooses (Herpestidae), several
      mustelids, and some skunks (Mephitidae). As a group, these taxa do not share any
      distinctive morphological traits. Instead, mammalian adaptations for ophiophagy
      seem to consist only in the ability to resist the toxic effects of snake venom.
      Molecular mechanisms of venom resistance (as indicated by biochemical research on
      opossums, mongooses, and hedgehogs) include toxin-neutralizing serum factors and
      adaptive changes in venom-targeted molecules. Of these, toxin-neutralizing serum
      factors have received the most research attention to date. All of the toxin
      neutralizing serum proteins discovered so far in both opossums and mongooses are
      human alpha1B-glycoprotein homologs that inhibit either snake-venom
      metalloproteinases or phospholipase A(2) myotoxins. By contrast, adaptive changes
      in venom-targeted molecules have received far less attention. The best-documented
      examples include amino-acid substitutions in mongoose nicotinic acetylcholine
      receptor that inhibit binding by alpha-neurotoxins, and amino-acid substitutions
      in opossum von Willebrand factor (vWF) that are hypothesized to weaken the bond
      between vWF and coagulopathic C-type lectins. Although multiple mechanisms of
      venom resistance are known from some species, the proteomic complexity of most
      snake venoms suggests that the evolved biochemical defences of ophiophagous
      mammals are likely to be far more numerous than currently recognized. Whereas
      most previous research in this field has been motivated by the potential for
      medical applications, venom resistance in ophiophagous mammals is a complex
      adaptation that merits attention from comparative biologists. Unfortunately,
      evolutionary inference is currently limited by ignorance about many relevant
      facts that can only be provided by future research.

PMID- 22404917
TI  - In silico optimization of atrial fibrillation-selective sodium channel blocker
      pharmacodynamics.
AB  - Atrial fibrillation (AF) is the most common type of clinical arrhythmia.
      Currently available anti-AF drugs are limited by only moderate efficacy and an
      unfavorable safety profile. Thus, there is a recognized need for improved
      antiarrhythmic agents with actions that are selective for the fibrillating
      atrium. State-dependent Na(+)-channel blockade potentially allows for the
      development of drugs with maximal actions on fibrillating atrial tissue and
      minimal actions on ventricular tissue at resting heart rates. In this study, we
      applied a mathematical model of state-dependent Na(+)-channel blocking (class I
      antiarrhythmic drug) action, along with mathematical models of canine atrial and
      ventricular cardiomyocyte action potentials, AF, and ventricular proarrhythmia,
      to determine the relationship between their pharmacodynamic properties and atrial
      selectivity, AF-selectivity (atrial Na(+)-channel block at AF rates versus
      ventricular block at resting rates), AF-termination effectiveness, and
      ventricular proarrhythmic properties. We found that drugs that target inactivated
      channels are AF-selective, whereas drugs that target activated channels are not.
      The most AF-selective drugs were associated with minimal ventricular
      proarrhythmic potential and terminated AF in 33% of simulations; slightly fewer
      AF-selective agents achieved termination rates of 100% with low ventricular
      proarrhythmic potential. Our results define properties associated with AF
      selective actions of class-I antiarrhythmic drugs and support the idea that it
      may be possible to develop class I antiarrhythmic agents with optimized
      pharmacodynamic properties for AF treatment.

PMID- 22404918
TI  - A new type of radical-pair-based model for magnetoreception.
AB  - Certain migratory birds can sense the Earth's magnetic field. The nature of this
      process is not yet properly understood. Here we offer a simple explanation
      according to which birds literally see the local magnetic field through the
      impact of a physical rather than a chemical signature of the radical pair: a
      transient, long-lived electric dipole moment. Based on this premise, our picture
      can explain recent surprising experimental data indicating long lifetimes for the
      radical pair. Moreover, there is a clear evolutionary path toward this field
      sensing mechanism: it is an enhancement of a weak effect that may be present in
      many species.

PMID- 22404919
TI  - Cell ingression and apical shape oscillations during dorsal closure in
      Drosophila.
AB  - Programmed patterns of gene expression, cell-cell signaling, and cellular forces
      cause morphogenic movements during dorsal closure. We investigated the apical
      cell-shape changes that characterize amnioserosa cells during dorsal closure in
      Drosophila embryos with in vivo imaging of green-fluorescent-protein-labeled DE
      cadherin. Time-lapsed, confocal images were assessed with a novel segmentation
      algorithm, Fourier analysis, and kinematic and dynamical modeling. We found two
      generic processes, reversible oscillations in apical cross-sectional area and
      cell ingression characterized by persistent loss of apical area. We quantified a
      time-dependent, spatially-averaged sum of intracellular and intercellular forces
      acting on each cell's apical belt of DE-cadherin. We observed that a substantial
      fraction of amnioserosa cells ingress near the leading edges of lateral
      epidermis, consistent with the view that ingression can be regulated by leading
      edge cells. This is in addition to previously observed ingression processes
      associated with zipping and apoptosis. Although there is cell-to-cell variability
      in the maximum rate for decreasing apical area (0.3-9.5 MUm(2)/min), the rate for
      completing ingression is remarkably constant (0.83 cells/min, r(2) > 0.99). We
      propose that this constant ingression rate contributes to the spatiotemporal
      regularity of mechanical stress exerted by the amnioserosa on each leading edge
      during closure.

PMID- 22404920
TI  - Modeling the step of endosomal escape during cell infection by a nonenveloped
      virus.
AB  - Widely disparate viruses enter the host cell through an endocytic pathway and
      travel the cytoplasm inside an endosome. For the viral genetic material to be
      delivered into the cytoplasm, these viruses have to escape the endosomal
      compartment, an event triggered by the conformational changes of viral
      endosomolytic proteins. We focus here on small nonenveloped viruses such as adeno
      associated viruses, which contain few penetration proteins. The first time a
      penetration protein changes conformation defines the slowest timescale
      responsible for the escape. To evaluate this time, we construct what to our
      knowledge is a novel biophysical model based on a stochastic approach that
      accounts for the small number of proteins, the endosomal maturation, and the
      protease activation dynamics. We show that the escape time increases with the
      endosomal size, whereas decreasing with the number of viral particles inside the
      endosome. We predict that the optimal escape probability is achieved when the
      number of proteases in the endosome is in the range of 250-350, achieved for
      three viral particles.

PMID- 22404921
TI  - Effects of convective transport on chemical signal propagation in epithelia.
AB  - We study effects of convective transport on a chemical front wave representing a
      signal propagation at a simple (single layer) epithelium by means of mathematical
      modeling. Plug flow and laminar flow regimes were considered. We observed a
      nonmonotonous dependence of the propagation velocity on the ligand receptor
      binding constant under influence of the convective transport. If the signal
      propagates downstream, the region of high velocities becomes much broader and
      spreads over several orders of magnitude of the binding constant. When the
      convective transport is oriented against the propagating signal, either velocity
      of the traveling front wave is slowed down or the traveling front wave can stop
      or reverse the direction of propagation. More importantly, chemical signal in
      epithelial systems influenced by the convective transport can propagate almost
      independently of the ligand-receptor binding constant in a broad range of this
      parameter. Furthermore, we found that the effects of the convective transport
      becomes more significant in systems where either the characteristic dimension of
      the extracellular space is larger/comparable with the spatial extent of the
      ligand diffusion trafficking or the ligand-receptor binding/ligand diffusion rate
      ratio is high.

PMID- 22404922
TI  - Landscape and global stability of nonadiabatic and adiabatic oscillations in a
      gene network.
AB  - We quantify the potential landscape to determine the global stability and
      coherence of biological oscillations. We explore a gene network motif in our
      experimental synthetic biology studies of two genes that mutually repress and
      activate each other with self-activation and self-repression. We find that in
      addition to intrinsic molecular number fluctuations, there is another type of
      fluctuation crucial for biological function: the fluctuation due to the slow
      binding/unbinding of protein regulators to gene promoters. We find that coherent
      limit cycle oscillations emerge in two regimes: an adiabatic regime with fast
      binding/unbinding and a nonadiabatic regime with slow binding/unbinding relative
      to protein synthesis/degradation. This leads to two mechanisms of producing the
      stable oscillations: the effective interactions from averaging the gene states in
      the adiabatic regime; and the time delays due to slow binding/unbinding to
      promoters in the nonadiabatic regime, which can be tested by forthcoming
      experiments. In both regimes, the landscape has a topological shape of the
      Mexican hat in protein concentrations that quantitatively determines the global
      stability of limit cycle dynamics. The oscillation coherence is shown to be
      correlated with the shape of the Mexican hat characterized by the height from the
      oscillation ring to the central top. The oscillation period can be tuned in a
      wide range by changing the binding/unbinding rate without changing the amplitude
      much, which is important for the functionality of a biological clock. A negative
      feedback loop with time delays due to slow binding/unbinding can also generate
      oscillations. Although positive feedback is not necessary for generating
      oscillations, it can make the oscillations more robust.

PMID- 22404923
TI  - Superoxide flashes reveal novel properties of mitochondrial reactive oxygen
      species excitability in cardiomyocytes.
AB  - Superoxide flash represents quantal and bursting production of mitochondrial
      reactive oxygen species (ROS) instigated by transient opening of the
      mitochondrial permeability transition pore (mPTP). Given their critical role in
      metabolism, ischemia-reperfusion injury, and apoptosis, characterization of flash
      properties would be valuable to further mechanistic and physiological studies of
      this newly discovered mitochondrial phenomenon. Here we developed the flash
      detector FlashSniper based on segmentation of two-dimensional feature maps
      extracted from time-lapse confocal image stacks, and on the theory for correcting
      optical distortion of flash-amplitude histograms. Through large-scale analysis of
      superoxide flashes in cardiomyocytes, we demonstrated uniform mitochondrial ROS
      excitability among subsarcolemmal and intermyofibrillar mitochondria, and
      exponential distribution of intervals between consecutive flash events. Flash
      ignition displayed three different patterns: an abrupt rise from quiescence
      (44%), a rise with an exponential foot (27%), or a rise occurring after a
      pedestal precursor (29%), closely resembling action-potential initiation in
      excitable cells. However, the optical blurring-corrected amplitudes of superoxide
      flashes were highly variable, as were their durations, indicating stochastic
      automaticity of single-mitochondrion ROS excitation. Simultaneous measurement of
      mitochondrial membrane potential revealed that graded, rather than all-or-none,
      depolarization mirrored the precursor and the primary peak of the flash. We
      propose that superoxide flash production is a regenerative process dominated by
      stochastic, autonomous recruitment of a limited number of units (e.g., mPTPs) in
      single mitochondria.

PMID- 22404925
TI  - Chemical and mechanical impact of silica nanoparticles on the phase transition
      behavior of phospholipid membranes in theory and experiment.
AB  - The interaction of nanoparticles (NPs) with lipid membranes is an integral step
      in the interaction of NPs and living cells. During particle uptake, the membrane
      has to bend. Due to the nature of their phase diagram, the modulus of compression
      of these membranes can vary by more than one order of magnitude, and thus both
      the thermodynamic and mechanical aspects of the membrane have to be considered
      simultaneously. We demonstrate that silica NPs have at least two independent
      effects on the phase transition of phospholipid membranes: 1), a chemical effect
      resulting from the finite instability of the NPs in water; and 2), a mechanical
      effect that originates from a bending of the lipid membrane around the NPs. Here,
      we report on recent experiments that allowed us to clearly distinguish both
      effects, and present a thermodynamic model that includes the elastic energy of
      the membranes and correctly predicts our findings both quantitatively and
      qualitatively.

PMID- 22404924
TI  - Aspartic acid residue D3 critically determines Cx50 gap junction channel
      transjunctional voltage-dependent gating and unitary conductance.
AB  - Previous studies have suggested that the aspartic acid residue (D) at the third
      position is critical in determining the voltage polarity of fast V(j)-gating of
      Cx50 channels. To test whether another negatively charged residue (a glutamic
      acid residue, E) could fulfill the role of the D3 residue, we generated the
      mutant Cx50D3E. V(j)-dependent gating properties of this mutant channel were
      characterized by double-patch-clamp recordings in N2A cells. Macroscopically, the
      D3E substitution reduced the residual conductance (G(min)) to near zero and
      outwardly shifted the half-inactivation voltage (V(0)), which is a result of both
      a reduced aggregate gating charge (z) and a reduced free-energy difference
      between the open and closed states. Single Cx50D3E gap junction channels showed
      reduced unitary conductance (gamma(j)) of the main open state, reduced open dwell
      time at +/-40 mV, and absence of a long-lived substate. In contrast, a G8E
      substitution tested to compare the effects of the E residue at the third and
      eighth positions did not modify the V(j)-dependent gating profile or gamma(j). In
      summary, this study is the first that we know of to suggest that the D3 residue
      plays an essential role, in addition to serving as a negative-charge provider, as
      a critical determinant of the V(j)-dependent gating sensitivity, open-closed
      stability, and unitary conductance of Cx50 gap junction channels.

PMID- 22404926
TI  - A novel dendrimeric peptide with antimicrobial properties: structure-function
      analysis of SB056.
AB  - The novel antimicrobial peptide with a dimeric dendrimer scaffold, SB056, was
      empirically optimized by high-throughput screening. This procedure produced an
      intriguing primary sequence whose structure-function analysis is described here.
      The alternating pattern of hydrophilic and hydrophobic amino acids suggests the
      possibility that SB056 is a membrane-active peptide that forms amphiphilic beta
      strands in a lipid environment. Circular dichroism confirmed that the cationic
      SB056 folds as beta-sheets in the presence of anionic vesicles. Lipid monolayer
      surface pressure experiments revealed unusual kinetics of monolayer penetration,
      which suggest lipid-induced aggregation as a membranolytic mechanism. NMR
      analyses of the linear monomer and the dendrimeric SB056 in water and in 30%
      trifluoroethanol, on the other hand, yielded essentially unstructured
      conformations, supporting the excellent solubility and storage properties of this
      compound. However, simulated annealing showed that many residues lie in the beta
      region of the Ramachandran plot, and molecular-dynamics simulations confirmed the
      propensity of this peptide to fold as a beta-type conformation. The excellent
      solubility in water and the lipid-induced oligomerization characteristics of this
      peptide thus shed light on its mechanism of antimicrobial action, which may also
      be relevant for systems that can form toxic beta-amyloid fibrils when in contact
      with cellular membranes. Functionally, SB056 showed high activity against Gram
      negative bacteria and some limited activity against Gram-positive bacteria. Its
      potency against Gram-negative strains was comparable (on a molar basis) to that
      of colistin and polymyxin B, with an even broader spectrum of activity than
      numerous other reference compounds.

PMID- 22404927
TI  - Actin network growth under load.
AB  - Many processes in eukaryotic cells, including the crawling motion of the whole
      cell, rely on the growth of branched actin networks from surfaces. In addition to
      their well-known role in generating propulsive forces, actin networks can also
      sustain substantial pulling loads thanks to their persistent attachment to the
      surface from which they grow. The simultaneous network elongation and surface
      attachment inevitably generate a force that opposes network growth. Here, we
      study the local dynamics of a growing actin network, accounting for simultaneous
      network elongation and surface attachment, and show that there exist several
      dynamical regimes that depend on both network elasticity and the kinetic
      parameters of actin polymerization. We characterize this in terms of a phase
      diagram and provide a connection between mesoscopic theories and the microscopic
      dynamics of an actin network at a surface. Our framework predicts the onset of
      instabilities that lead to the local detachment of the network and translate to
      oscillatory behavior and waves, as observed in many cellular phenomena and in
      vitro systems involving actin network growth, such as the saltatory dynamics of
      actin-propelled oil drops.

PMID- 22404928
TI  - How type II diabetes-related islet amyloid polypeptide damages lipid bilayers.
AB  - A leading hypothesis for the decimation of insulin-producing beta-cells in type 2
      diabetes attributes the cause to islet amyloid polypeptide (IAPP) for its
      deleterious effects on the cell membranes. This idea has produced extensive
      investigations on human IAPP (hIAPP) and its interactions with lipid bilayers.
      However, it is still difficult to correlate the peptide-lipid interactions with
      its effects on islet cells in culture. The hIAPP fibrils have been shown to
      interact with lipids and damage lipid bilayers, but appear to have no effect on
      islet cells in culture. Thus, a modified amyloid hypothesis assumes that the
      toxicity is caused by hIAPP oligomers, which are not preamyloid fibrils or
      protofibrils. However, so far such oligomers have not been isolated or
      identified. The hIAPP monomers also bind to lipid bilayers, but the mode of
      interaction is not clear. Here, we performed two types of experiments that, to
      our knowledge, have not been done before. We used x-ray diffraction, in
      conjunction with circular dichroism measurement, to reveal the location of the
      peptide bound to a lipid bilayer. We also investigated the effects of hIAPP on
      giant unilamellar vesicles at various peptide concentrations. We obtained the
      following qualitative results. Monomeric hIAPP binds within the headgroup region
      and expands the membrane area of a lipid bilayer. At low concentrations, such
      binding causes no leakage or damage to the lipid bilayer. At high concentrations,
      the bound peptides transform to beta-aggregates. The aggregates exit the
      headgroup region and bind to the surface of lipid bilayers. The damage by the
      surface bound beta-aggregates depends on the aggregation size. The initial
      aggregation extracts lipid molecules, which probably causes ion permeation, but
      no molecular leakage. However, the initial beta-aggregates serve as the seed for
      larger fibrils, in the manner of the Jarrett-Lansbury seeded-polymerization
      model, that eventually disintegrate lipid bilayers by electrostatic and
      hydrophobic interactions.

PMID- 22404929
TI  - Membrane clustering and the role of rebinding in biochemical signaling.
AB  - In many cellular signaling pathways, key components form clusters at the cell
      membrane. Although much work has focused on the mechanisms behind such cluster
      formation, the implications for downstream signaling remain poorly understood.
      Here, motivated by recent experiments, we use particle-based simulation to study
      a covalent modification network in which the activating component is either
      clustered or randomly distributed on the membrane. We find that whereas
      clustering reduces the response of a single-modification network, it can enhance
      the response of a double-modification network. The reduction is a bulk effect: a
      cluster presents a smaller effective target to a substrate molecule in the bulk.
      The enhancement, on the other hand, is a local effect: a cluster promotes the
      rapid rebinding and second activation of singly activated substrate molecules. As
      such, the enhancement relies on frequent collisions on a short timescale, leading
      to an optimal ratio of diffusion to association that agrees with typical measured
      rates. We complement simulation with analytic results at both the mean-field and
      first-passage distribution levels. Our results emphasize the importance of
      spatially resolved models, showing that significant effects of spatial
      correlations persist even in spatially averaged quantities such as response
      curves.

PMID- 22404930
TI  - Thermodynamics of phospholipid self-assembly.
AB  - Negatively charged phospholipids are an important component of biological
      membranes. The thermodynamic parameters governing self-assembly of anionic
      phospholipids are deduced here from isothermal titration calorimetry. Heats of
      demicellization were determined for dioctanoyl phosphatidylglycerol (PG) and
      phosphatidylserine (PS) at different ionic strengths, and for dioctanoyl
      phosphatidic acid at different pH values. The large heat capacity (DeltaC degrees
      (P) ~ -400 J.mol(-1) K(-1) for PG and PS), and zero enthalpy at a characteristic
      temperature near the physiological range (T(*) ~ 300 K for PG and PS),
      demonstrate that the driving force for self-assembly is the hydrophobic effect.
      The pH and ionic-strength dependences indicate that the principal electrostatic
      contribution to self-assembly comes from the entropy associated with the
      electrostatic double layer, in agreement with theoretical predictions. These
      measurements help define the thermodynamic effects of anionic lipids on
      biomembrane stability.

PMID- 22404931
TI  - Three distinct actin-attached structural states of myosin in muscle fibers.
AB  - We have used thiol cross-linking and electron paramagnetic resonance (EPR) to
      resolve structural transitions of myosin's light chain domain (LCD) and catalytic
      domain (CD) that are associated with force generation. Spin labels were
      incorporated into the LCD of muscle fibers by exchanging spin-labeled regulatory
      light chain for endogenous regulatory light chain, with full retention of
      function. To trap myosin in a structural state analogous to the elusive
      posthydrolysis ternary complex A.M'.D.P, we used pPDM to cross-link SH1
      (Cys(707)) to SH2 (Cys(697)) on the CD. LCD orientation and dynamics were
      measured in three biochemical states: relaxation (A.M.T), SH1-SH2 cross-linked
      (A.M'.D.P analog), and rigor (A.M.D). EPR showed that the LCD of cross-linked
      fibers has an orientational distribution intermediate between relaxation and
      rigor, and saturation transfer EPR revealed slow rotational dynamics
      indistinguishable from that of rigor. Similar results were obtained for the CD
      using a bifunctional spin label to cross-link SH1-SH2, but the CD was more
      disordered than the LCD. We conclude that SH1-SH2 cross-linking traps a state in
      which both the CD and LCD are intermediate between relaxation (highly disordered
      and microsecond dynamics) and rigor (highly ordered and rigid), supporting the
      hypothesis that the cross-linked state is an A.M'D.P analog on the force
      generation pathway.

PMID- 22404932
TI  - Thermodynamic and kinetic analysis of an RNA kissing interaction and its
      resolution into an extended duplex.
AB  - Kissing hairpin interactions form when the loop residues of two hairpins have
      Watson-Crick complementarity. In a unimolecular context, kissing interactions are
      important for tertiary folding and pseudoknot formation, whereas in a bimolecular
      context, they provide a basis for molecular recognition. In some cases, kissing
      complexes can be a prelude to strand displacement reactions where the two
      hairpins resolve to form a stable extended intermolecular duplex. The kinetics
      and thermodynamics of kissing-complex formation and their subsequent strand
      displacement reactions are poorly understood. Here, biophysical techniques
      including isothermal titration calorimetry, surface plasmon resonance, and single
      molecule fluorescence have been employed to probe the factors that govern the
      stability of kissing complexes and their subsequent structural rearrangements. We
      show that the general understanding of RNA duplex formation can be extended to
      kissing complexes but that kissing complexes display an unusual level of
      stability relative to simple duplexes of the same sequence. These interactions
      form and break many times at room temperature before becoming committed to a
      slow, irreversible forward transition to the strand-displaced form. Furthermore,
      using smFRET we show that the primary difference between stable and labile
      kissing complexes is based almost completely on their off rates. Both stable and
      labile complexes form at the same rate within error, but less stable species
      dissociate rapidly, allowing us to understand how these complexes can help
      generate specificity along a folding pathway or during a gene regulation event.

PMID- 22404933
TI  - Functional domain motions in proteins on the ~1-100 ns timescale: comparison of
      neutron spin-echo spectroscopy of phosphoglycerate kinase with molecular-dynamics
      simulation.
AB  - Protein function often requires large-scale domain motion. An exciting new
      development in the experimental characterization of domain motions in proteins is
      the application of neutron spin-echo spectroscopy (NSE). NSE directly probes
      coherent (i.e., pair correlated) scattering on the ~1-100 ns timescale. Here, we
      report on all-atom molecular-dynamics (MD) simulation of a protein,
      phosphoglycerate kinase, from which we calculate small-angle neutron scattering
      (SANS) and NSE scattering properties. The simulation-derived and experimental
      solution SANS results are in excellent agreement. The contributions of
      translational and rotational whole-molecule diffusion to the simulation-derived
      NSE and potential problems in their estimation are examined. Principal component
      analysis identifies types of domain motion that dominate the internal motion's
      contribution to the NSE signal, with the largest being classic hinge bending. The
      associated free-energy profiles are quasiharmonic and the frictional properties
      correspond to highly overdamped motion. The amplitudes of the motions derived by
      MD are smaller than those derived from the experimental analysis, and possible
      reasons for this difference are discussed. The MD results confirm that a
      significant component of the NSE arises from internal dynamics. They also
      demonstrate that the combination of NSE with MD is potentially useful for
      determining the forms, potentials of mean force, and time dependence of
      functional domain motions in proteins.

PMID- 22404934
TI  - Mechanical anisotropy of ankyrin repeats.
AB  - Red blood cells are frequently deformed and their cytoskeletal proteins such as
      spectrin and ankyrin-R are repeatedly subjected to mechanical forces. While the
      mechanics of spectrin was thoroughly investigated in vitro and in vivo, little is
      known about the mechanical behavior of ankyrin-R. In this study, we combine
      coarse-grained steered molecular dynamics simulations and atomic force
      spectroscopy to examine the mechanical response of ankyrin repeats (ARs) in a
      model synthetic AR protein NI6C, and in the D34 fragment of native ankyrin-R when
      these proteins are subjected to various stretching geometry conditions. Our
      steered molecular dynamics results, supported by AFM measurements, reveal an
      unusual mechanical anisotropy of ARs: their mechanical stability is greater when
      their unfolding is forced to propagate from the N-terminus toward the C-terminus
      (repeats unfold at ~60 pN), as compared to the unfolding in the opposite
      direction (unfolding force ~ 30 pN). This anisotropy is also reflected in the
      complex refolding behavior of ARs. The origin of this unfolding and refolding
      anisotropy is in the various numbers of native contacts that are broken and
      formed at the interfaces between neighboring repeats depending on the
      unfolding/refolding propagation directions. Finally, we discuss how these complex
      mechanical properties of ARs in D34 may affect its behavior in vivo.

PMID- 22404935
TI  - Supramolecular non-amyloid intermediates in the early stages of alpha-synuclein
      aggregation.
AB  - The aggregation of alpha-synuclein is associated with progression of Parkinson's
      disease. We have identified submicrometer supramolecular structures that mediate
      the early stages of the overall mechanism. The sequence of structural
      transformations between metastable intermediates were captured and characterized
      by atomic force microscopy guided by a fluorescent probe sensitive to preamyloid
      species. A novel ~0.3-0.6 MUm molecular assembly, denoted the acuna, nucleates,
      expands, and liberates fibers with distinctive segmentation and a filamentous
      fuzzy fringe. These fuzzy fibers serve as precursors of mature amyloid fibrils.
      Cryo-electron tomography resolved the acuna inner structure as a scaffold of
      highly condensed colloidal masses interlinked by thin beaded threads, which were
      perceived as fuzziness by atomic force microscopy. On the basis of the combined
      data, we propose a sequential mechanism comprising molecular, colloidal, and
      fibrillar stages linked by reactions with disparate temperature dependencies and
      distinct supramolecular forms. We anticipate novel diagnostic and therapeutic
      approaches to Parkinson's and related neurodegenerative diseases based on these
      new insights into the aggregation mechanism of alpha-synuclein and intermediates,
      some of which may act to cause and/or reinforce neurotoxicity.

PMID- 22404936
TI  - Epinephrine modulates BCAM/Lu and ICAM-4 expression on the sickle cell trait red
      blood cell membrane.
AB  - Collapse and sudden death in physical training are the most serious complications
      of sickle cell trait (SCT). There is evidence that erythrocytes in SCT patients
      aggregate during strenuous exercise, likely because of adhesive interactions with
      the extracellular matrix (ECM) and endothelial cells, and because of their
      irregular viscoelastic properties. This results in inflammation, blood flow
      impairment, and vaso-occlusive events. However, the exact role of stress
      conditions and how they lead to these complications is virtually unknown. Using
      single-molecule atomic force microscopy experiments, we found that epinephrine, a
      hormone that is secreted under stressful conditions, increases both the frequency
      and strength of adhesion events between basal cell adhesion molecule (BCAM/Lu)
      and ECM laminin, and between intercellular adhesion molecule-4 (ICAM-4) and
      endothelial alpha(v)beta(3), compared with nonstimulated SCT erythrocytes.
      Increases in adhesion frequency provide significant evidence of the role of
      epinephrine in BCAM/Lu-laminin and ICAM-4-alpha(v)beta(3) bonding, and suggest
      mechanisms of vaso-occlusion during physical exertion in SCT.

PMID- 22404937
TI  - Spectral analysis methods for the robust measurement of the flexural rigidity of
      biopolymers.
AB  - The mechanical properties of biopolymers can be determined from a statistical
      analysis of the ensemble of shapes they exhibit when subjected to thermal forces.
      In practice, extracting information from fluorescence microscopy images can be
      challenging due to low signal/noise ratios and other artifacts. To address these
      issues, we develop a suite of tools for image processing and spectral data
      analysis that is based on a biopolymer contour representation expressed in a
      spectral basis of orthogonal polynomials. We determine biopolymer shape and
      stiffness using global fitting routines that optimize a utility function
      measuring the amount of fluorescence intensity overlapped by such contours. This
      approach allows for filtering of high-frequency noise and interpolation over
      sporadic gaps in fluorescence. We use benchmarking to demonstrate the validity of
      our methods, by analyzing an ensemble of simulated images generated using a
      simulated biopolymer with known stiffness and subjected to various types of image
      noise. We then use these methods to determine the persistence lengths of taxol
      stabilized microtubules. We find that single microtubules are well described by
      the wormlike chain polymer model, and that ensembles of chemically identical
      microtubules show significant heterogeneity in bending stiffness, which cannot be
      attributed to sampling or fitting errors. We expect these approaches to be useful
      in the study of biopolymer mechanics and the effects of associated regulatory
      molecules.

PMID- 22404938
TI  - Enrichment of amyloidogenesis at an air-water interface.
AB  - The aggregation of proteins or peptides into amyloid fibrils is a hallmark of
      protein misfolding diseases (e.g., Alzheimer's disease) and is under intense
      investigation. Many of the experiments performed are in vitro in nature and the
      samples under study are ordinarily exposed to diverse interfaces, e.g., the
      container wall and air. This naturally raises the question of how important
      interfacial effects are to amyloidogenesis. Indeed, it has already been
      recognized that many amyloid-forming peptides are surface-active. Moreover, it
      has recently been demonstrated that the presence of a hydrophobic interface can
      promote amyloid fibrillization, although the underlying mechanism is still
      unclear. Here, we combine theory, surface property measurements, and amyloid
      fibrillogenesis assays on islet amyloid polypeptide and amyloid-beta peptide to
      demonstrate why, at experimentally relevant concentrations, the surface activity
      of the amyloid-forming peptides leads to enriched fibrillization at an air-water
      interface. Our findings indicate that the key that links these two seemingly
      different phenomena is the surface-active nature of the amyloid-forming species,
      which renders the surface concentration much higher than the corresponding
      critical fibrillar concentration. This subsequently leads to a substantial
      increase in fibrillization.

PMID- 22404939
TI  - Disentangling subpopulations in single-molecule FRET and ALEX experiments with
      photon distribution analysis.
AB  - Among the advantages of the single-molecule approach when used to study
      biomolecular structural dynamics and interaction is its ability to distinguish
      between and independently observe minor subpopulations. In a single-molecule
      Forster resonance energy transfer (FRET) and alternating laser excitation
      diffusion experiment, the various populations are apparent in the resultant
      histograms. However, because histograms are calculated based on the per-burst
      mean FRET and stoichiometry ratio and not on the internal photon distribution,
      much of the acquired information is lost, thereby reducing the capabilities of
      the method. Here we suggest what to our knowledge is a novel statistical analysis
      tool that significantly enhances these capabilities, and we use it to identify
      and isolate static and dynamic subpopulations. Based on a kernel density
      estimator and a proper photon distribution analysis, for each individual burst,
      we calculate scores that reflect properties of interest. Specifically, we
      determine the FRET efficiency and brightness ratio distributions and use them to
      reveal 1), the underlying structure of a two-state DNA-hairpin and a DNA hairpin
      that is bound to DNA origami; 2), a minor doubly labeled dsDNA subpopulation
      concealed in a larger singly labeled dsDNA; and 3), functioning DNA origami
      motors concealed within a larger subpopulation of defective motors. Altogether,
      these findings demonstrate the usefulness of the proposed approach. The method
      was developed and tested using simulations, its rationality is described, and a
      computer algorithm is provided.

PMID- 22404940
TI  - Factors affecting the quantification of biomolecular interactions by fluorescence
      cross-correlation spectroscopy.
AB  - Fluorescence cross-correlation spectroscopy (FCCS) is used to determine
      interactions and dissociation constants (K(d)s) of biomolecules. The
      determination of a K(d) depends on the accurate measurement of the auto- and
      cross-correlation function (ACF and CCF) amplitudes. In the case of complete
      binding, the ratio of the CCF/ACF amplitudes is expected to be 1. However,
      measurements performed on tandem fluorescent proteins (FPs), in which two
      different FPs are linked, yield CCF/ACF amplitude ratios of ~0.5 or less for
      different FCCS schemes. We use single wavelength FCCS and pulsed interleaved
      excitation FCCS to measure various tandem FPs constituted of different red and
      green FPs and determine the causes for this suboptimal ratio. The main causes for
      the reduced CCF/ACF amplitude ratio are differences in observation volumes for
      the different labels, the existence of dark FPs due to maturation problems,
      photobleaching, and to a lesser extent Forster (or fluorescence) resonance energy
      transfer between the labels. We deduce the fraction of nonfluorescent proteins
      for EGFP, mRFP, and mCherry as well as the differences in observation volumes. We
      use this information to correct FCCS measurements of the interaction of Cdc42, a
      small Rho-GTPase, with its effector IQGAP1 in live cell measurements to obtain a
      label-independent value for the K(d).

PMID- 22404941
TI  - Hidden multiple bond effects in dynamic force spectroscopy.
AB  - In dynamic force spectroscopy, a (bio-)molecular complex is subjected to a
      steadily increasing force until the chemical bond breaks. Repeating the same
      experiment many times results in a broad distribution of rupture forces, whose
      quantitative interpretation represents a formidable theoretical challenge. In
      this study we address the situation that more than a single molecular bond is
      involved in one experimental run, giving rise to multiple rupture events that are
      even more difficult to analyze and thus are usually eliminated as far as possible
      from the further evaluation of the experimental data. We develop and numerically
      solve a detailed model of a complete dynamic force spectroscopy experiment
      including a possible clustering of molecules on the substrate surface, the
      formation of bonds, their dissociation under load, and the postprocessing of the
      force extension curves. We show that the data, remaining after elimination of
      obvious multiple rupture events, may still contain a considerable number of
      hidden multiple bonds, which are experimentally indistinguishable from true
      single bonds, but which have considerable effects on the resulting rupture force
      statistics and its consistent theoretical interpretation.

PMID- 22404942
TI  - Measurement of the mitochondrial membrane potential and pH gradient from the
      redox poise of the hemes of the bc1 complex.
AB  - The redox potentials of the hemes of the mitochondrial bc(1) complex are
      dependent on the proton-motive force due to the energy transduction. This allows
      the membrane potential and pH gradient components to be calculated from the
      oxidation state of the hemes measured with multi-wavelength cell spectroscopy.
      Oxidation states were measured in living RAW 264.7 cells under varying electron
      flux and membrane potential obtained by a combination of oligomycin and titration
      with a proton ionophore. A stochastic model of bc(1) turnover was used to confirm
      that the membrane potential and redox potential of the ubiquinone pool could be
      measured from the redox poise of the b-hemes under physiological conditions
      assuming the redox couples are in equilibrium. The pH gradient was then
      calculated from the difference in redox potentials of cytochrome c and ubiquinone
      pool using the stochastic model to evaluate the DeltaG of the bc(1) complex. The
      technique allows absolute quantification of the membrane potential, pH gradient,
      and proton-motive force without the need for genetic manipulation or exogenous
      compounds.

PMID- 22404943
TI  - In vivo imaging of the actin polymerization state with two-photon fluorescence
      anisotropy.
AB  - Using two-photon fluorescence anisotropy imaging of actin-GFP, we have developed
      a method for imaging the actin polymerization state that is applicable to a broad
      range of experimental systems extending from fixed cells to live animals. The
      incorporation of expressed actin-GFP monomers into endogenous actin polymers
      enables energy migration FRET (emFRET, or homoFRET) between neighboring actin
      GFPs. This energy migration reduces the normally high polarization of the GFP
      fluorescence. We derive a simple relationship between the actin-GFP fluorescence
      polarization anisotropy and the actin polymer fraction, thereby enabling a robust
      means of imaging the actin polymerization state with high spatiotemporal
      resolution and providing what to the best of our knowledge are the first direct
      images of the actin polymerization state in live, adult brain tissue and live,
      intact Drosophila larvae.

PMID- 22404944
TI  - Label-free analysis of breast tissue polarity by Raman imaging of lipid phase.
AB  - The formation of the basoapical polarity axis in epithelia is critical for
      maintaining the homeostasis of differentiated tissues. Factors that influence
      cancer development notoriously affect tissue organization. Apical polarity
      appears as a specific tissue feature that, once disrupted, would facilitate the
      onset of mammary tumors. Thus, developing means to rapidly measure apical
      polarity alterations would greatly favor screening for factors that endanger the
      breast epithelium. A Raman scattering-based platform was used for label-free
      determination of apical polarity in live breast glandular structures (acini)
      produced in three-dimensional cell culture. The coherent anti-Stokes Raman
      scattering signal permitted the visualization of the apical and basal surfaces of
      an acinus. Raman microspectroscopy subsequently revealed that polarized acini
      lipids were more ordered at the apical membranes compared to basal membranes, and
      that an inverse situation occurred in acini that lost apical polarity upon
      treatment with Ca(2+)-chelator EGTA. This method overcame variation between
      different cultures by tracking the status of apical polarity longitudinally for
      the same acini. Therefore, the disruption of apical polarity by a dietary breast
      cancer risk factor, omega6 fatty acid, could be observed with this method, even
      when the effect was too moderate to permit a conclusive assessment by the
      traditional immunostaining method.

PMID- 22404946
TI  - Nanoscale organization of junctophilin-2 and ryanodine receptors within
      peripheral couplings of rat ventricular cardiomyocytes.
AB  - The peripheral distributions of the cardiac ryanodine receptor (RyR) and a
      junctional protein, junctophilin-2 (JPH2), were examined using single fluorophore
      localization-based super-resolution microscopy in rat ventricular myocytes. JPH2
      was strongly associated with RyR clusters. Estimates of the colocalizing fraction
      of JPH labeling with RyR was ~90% within 30 nm of RyR clusters. This is
      comparable to fractions estimated from confocal data (~87%). Similarly, most RyRs
      were associated with JPH2 labeling in super-resolution images (~81% within 30 nm
      of JPH2 clusters). The shape of associated RyR clusters and JPH2 clusters were
      very similar, but not identical, suggesting that JPH2 is dispersed throughout RyR
      clusters and that the packing of JPH2 into junctions and the assembly of RyR
      clusters are tightly linked.

PMID- 22404945
TI  - The influence of a biologically relevant substratum topography on human aortic
      and umbilical vein endothelial cells.
AB  - A topographically patterned substrate with stochastic surface order that closely
      mimics the topographic features of native basement membranes has been fabricated
      to investigate the influence of topographic biophysical cueing on human aortic
      and umbilical vein endothelial cells. The stochastic substrate was fabricated by
      first generating a highly porous polyelectrolyte multilayer film of poly(acrylic
      acid) and poly(allylamine hydrochloride) followed by replicate production of this
      biomimetic topography via soft lithography. These substrates, which are easy to
      prepare and replicate, possess a number of prominent features associated with in
      vivo vascular basement membrane (interwoven ridges and grooves, bumps, and
      pores), which have typically been studied as singular features that frequently
      possess anisotropic surface order (e.g., alternating ridges and grooves). When
      compared to a flat surface of identical chemistry, these biomimetic topographies
      influenced a number of important cellular behaviors associated with the
      homeostasis and degradation of vascular tissues. These include modulating cell
      migration rate and directional persistence, proliferation rate, and gene
      expression associated with regulation and remodeling of vascular tissues as well
      as inflammation.

PMID- 22404947
TI  - Epithelial-mesenchymal transition as a fundamental mechanism underlying the
      cancer phenotype.
AB  - Epithelial-mesenchymal transition (EMT) is a complex process involved in
      embryonic development, wound healing and carcinogenesis. During this process,
      epithelial cells lose their defining characteristics and acquire mesenchymal
      properties: loss of cell-cell adhesion; increased motility and invasiveness;
      resistance to apoptosis and changes in cellular morphology. EMT has been
      implicated as a driver of metastasis and tumour invasion, as this process allows
      cells to detach from their niche and migrate through blood and lymphatic vessels
      to invade different organs. This transition involves a diverse range of
      transcription factors, including Twist, Snail and ZEB1, and downstream
      transcriptional targets, including E-cadherin, beta-catenin, fibronectin and
      vimentin. Recent evidence indicates that cancer stem cells are required for
      metastatic tumours to become established at a distant site, and that cancer cells
      undergoing EMT may develop stem-cell characteristics as well as increased
      invasive potential. The role of EMT in cancer biology is newly emerging in the
      human field, and to date very little has been done in veterinary medicine. EMT
      may therefore be an important molecular determinant of tumour metastasis, and
      further understanding of this process may lead to novel drug targets to be
      exploited in both veterinary and human medicine. 

PMID- 22404948
TI  - A review of the burden of disease due to otitis media in the Asia-Pacific.
AB  - OBJECTIVE: The burden of disease due to otitis media (OM) in Asia Pacific
      countries was reviewed to increase awareness and raise understanding within the
      region. METHODS: Published literature and unpublished studies were reviewed.
      RESULTS: In school-age children, OM prevalence varied between 3.25% (Thailand)
      and 12.23% (Philippines) being highest (42%) in Aboriginal Australian children.
      OME prevalence at school age varied between 1.14% (Thailand) and 13.8%
      (Malaysia). Higher prevalence was reported in children with hearing impairment,
      HIV, pneumonia and rhinitis. CSOM prevalence was 5.4% in Indonesia (all ages),
      15% in Aboriginal Australian children and 2-4% in Thailand, Philippines, Malaysia
      and Vietnam (WHO estimate). OM prevalence/incidence and service utilisation were
      highest in children 2-5 years of age. The disease burden was substantially higher
      in Pacific Island children living in New Zealand (25.4% with OME), and was
      highest in indigenous Australians (>90% with any OM). Streptococcus pneumoniae
      and Haemophilus influenzae dominated as primary causes of AOM in all studies. Few
      studies examined pneumococcal serotype distribution. Health-related cost
      estimates for OM, when available, were substantial. In developing countries,
      significant investment is needed to provide facilities for detection and
      treatment of ear disease in children, if long term hearing deficits and other
      sequelae are to be prevented. CONCLUSION: The available evidence suggests an
      important burden of disease and economic cost associated with OM in most Asia
      Pacific countries and a potential benefit of prevention through vaccination.
      Large, prospective community-based studies are needed to better define the
      prevalence of ear disease in children, and to predict and track pneumococcal
      conjugate vaccine impacts. AOM prevention through vaccination may also provide a
      means of reducing antibiotic use and controlling antibiotic-resistant disease in
      children. This review highlights the need for additional research, and provides a
      basis on which to build and develop regional guidelines for OM management.

PMID- 22404949
TI  - Concomitant Waldenstrom macroglobulinemia and IgA plasmablastic myeloma in a
      patient with untreated IgM paraproteinemia: sequential development of biclonal B
      cell neoplasms over a 10-year period in a single individual.
AB  - Waldenstrom macroglobulinemia and plasma cell myeloma are both mature B-cell
      neoplasms primarily involving bone marrow and frequently demonstrating
      paraproteinemia. Plasma cell myeloma has been described in association with other
      indolent B-cell lymphomas, particularly chronic lymphocytic leukemia, but
      concomitant Waldenstrom macroglobulinemia and plasma cell myeloma has not been
      previously described. We report the first case of sequential development of
      Waldenstrom macroglobulinemia and plasma cell myeloma over a 10-year period in a
      73-year-old man with untreated IgM paraproteinemia. The bone marrow biopsy
      demonstrated dual populations of lymphoid cells: small mature lymphocytes and
      immature plasma cells. Although both Waldenstrom macroglobulinemia and plasma
      cell myeloma were restricted to kappa light chain, plasma cell myeloma expressed
      IgA, whereas the plasmacytic component in Waldenstrom macroglobulinemia produced
      IgM. The biclonal nature of these 2 B-cell neoplasms was further supported by
      immunofixation electrophoresis and cytogenetic studies. Although the clinical
      outcome of plasma cell myeloma when concomitant with other indolent B-cell
      neoplasms is unfavorable, our patient seemed to respond to high-dose bortezomib
      plus lenalidomide.

PMID- 22404950
TI  - Morphologic and immunophenotypic analysis of desmoid-type fibromatosis after
      radiation therapy.
AB  - The morphologic changes seen in desmoid-type fibromatosis after radiotherapy have
      not been well studied, and the degree of cytologic atypia, cellularity, mitotic
      activity, and lesional necrosis found in desmoid-type fibromatosis treated with
      ionizing radiation has not been thoroughly assessed. Therefore, we evaluated a
      series of primary and locally recurrent desmoid-type fibromatoses resected at
      variable intervals after radiation therapy (XRT) and compared their
      histopathologic and immunophenotypic features with paired pathologic specimens
      that were obtained before radiotherapy. The morphologic characteristics of
      desmoid-type fibromatoses resected before and after radiotherapy were not
      significantly different in 7 of the 8 cases studied. One case resected 191 months
      after XRT showed morphologic evidence of fibrosarcomatous transformation, with
      zonal necrosis, hypercellularity, severe nuclear atypia, and increased mitotic
      activity. No significant differences in the immunophenotype of desmoid-type
      fibromatosis were observed after XRT. In rare cases of recurrent desmoid-type
      fibromatosis, the differential diagnosis may include radiation-induced
      fibrosarcoma. Our data suggest that histomorphologic alterations attributable to
      the effects of ionizing radiation in desmoid-type fibromatosis are minimal.
      Therefore, the presence of cytologic features of malignancy in this setting
      warrants careful examination and consideration of the rare occurrence of
      postradiation sarcoma. Lesser degrees of nuclear atypia seen in isolation do not
      necessarily indicate a poor prognosis in irradiated desmoid-type fibromatosis.

PMID- 22404952
TI  - Postpartum depression and intimate partner violence in urban mothers: co
      occurrence and child healthcare utilization.
AB  - OBJECTIVE: To assess the prevalence, timing, and co-occurrence of positive
      screens for maternal postpartum depression and intimate partner violence and
      examine their relationships with children's healthcare utilization from birth to
      2 years. STUDY DESIGN: Between February and March 2008, mothers bringing newborn,
      2-, 4-, or 6-month-old children to an urban primary care clinic were screened for
      postpartum depression and intimate partner violence. A retrospective chart review
      abstracted demographic data, maternal responses on the postpartum
      depression/intimate partner violence screen at the initial and subsequent visits,
      and, from the child's birth to second birthday, adherence with well-child care
      and use of pediatric acute care and emergency department visits. Descriptive,
      bivariate, and multivariate analyses were conducted. RESULTS: A total of 173
      mothers completed at least one postpartum depression/intimate partner violence
      screening survey. Overall, 26% screened positive for postpartum depression and 7%
      screened positive for intimate partner violence; most positive screens occurred
      at the initial visit. About 60% of mothers with a positive intimate partner
      violence screen also had a positive postpartum depression screen. Well-child care
      adherence and acute care visit utilization were not associated with maternal
      postpartum depression/intimate partner violence screening. Children of women with
      a positive screen for postpartum depression had greater emergency department
      utilization. CONCLUSION: The co-occurrence of postpartum depression and intimate
      partner violence is high in urban mothers. Primary care providers should
      routinely screen for both problems in this population and recognize the
      importance of screening for one problem if the other problem is identified.

PMID- 22404951
TI  - Quorum sensing modulates colony morphology through alkyl quinolones in
      Pseudomonas aeruginosa.
AB  - BACKGROUND: Acyl-homoserine lactone (acyl-HSL) and alkyl quinolone (AQ) based
      quorum-sensing (QS) systems are important for Pseudomonas aeruginosa virulence
      and biofilm formation. The effect of QS on biofilm formation is influenced by
      various genetic and environmental factors. Here, we used a colony biofilm assay
      to study the effect of the central acyl-HSL QS regulator, LasR, on biofilm
      formation and structure in the representative clinical P. aeruginosa isolate
      ZK2870. RESULTS: A lasR mutant exhibited wrinkled colony morphology at 37 degrees
      C in contrast to the smooth colony morphology of the wild-type. Mutational
      analysis indicated that wrinkling of the lasR mutant is dependent on pel,
      encoding a biofilm matrix exopolysaccharide. Suppressor mutagenesis and
      complementation analysis implicated the AQ signaling pathway as the link between
      las QS and colony morphology. In this pathway, genes pqsA-D are involved in the
      synthesis of 4-hydroxyalkyl quinolines ("Series A congeners"), which are
      converted to 3,4-dihydroxyalkyl quinolines ("Series B congeners", including the
      well-characterized Pseudomonas Quinolone Signal, PQS) by the product of the LasR
      dependent pqsH gene. Measurement of AQ in the wild-type, the lasR pqsA::Tn
      suppressor mutant as well as the defined lasR, pqsH, and lasR pqsH mutants showed
      a correlation between 4-hydroxyalkyl quinoline levels and the degree of colony
      wrinkling. Most importantly, the lasR pqsH double mutant displayed wrinkly
      morphology without producing any 3,4-dihydroxyalkyl quinolines. Constitutive
      expression of pqsA-D genes in a lasR pqsR::Tnmutant showed that colony wrinkling
      does not require the AQ receptor PqsR. CONCLUSIONS: Taken together, these results
      indicate that the las QS system represses Pel and modulates colony morphology
      through a 4-hydroxyalkyl quinoline in a PqsR-independent manner, ascribing a
      novel function to an AQ other than PQS in P. aeruginosa.

PMID- 22404953
TI  - Skin lesions and lung cysts in a neonate.

PMID- 22404954
TI  - Prevalence of hyponatremia at diagnosis and factors associated with the
      longitudinal variation in serum sodium levels in infants with cystic fibrosis.
AB  - OBJECTIVE: To determine the prevalence of hyponatremia at diagnosis in patients
      with cystic fibrosis and identify the factors associated with changes in serum
      sodium concentration over time. STUDY DESIGN: This longitudinal study
      investigated whether variations in serum sodium concentration were associated
      with age, diet, infection status, and climate/temperature. Multivariate analysis
      was performed using the random-effects model for longitudinal data. RESULTS:
      Hyponatremia at diagnosis was observed in 19 of the 20 patients (95%). Factors
      identified as associated with variations in serum sodium concentration were diet
      (P = .008) and climate/temperature (P = .005). Intake of solid foods appeared to
      greatly increase the serum sodium concentration (increase of 5 mEq/L after
      introduction of solid foods); however, a confounding factor between diet and age
      cannot be definitively ruled out. Climate/temperature contributed in an inverse
      way; a 1 degrees C-increase in ambient temperature was associated with a 0.5
      mEq/L decrease in serum sodium concentration. CONCLUSION: Infants with cystic
      fibrosis who feed on breast milk or formula and live in a high-temperature
      environment are at increased risk for hyponatremia, even when receiving a higher
      salt intake in accordance with recommendations.

PMID- 22404955
TI  - The value of positron emission tomography in early detection of lung cancer in
      high-risk population: a systematic review.
AB  - BACKGROUND: Early detection trials with chest radiography and sputum cytology
      were ineffective in decreasing lung cancer mortality. The advent of low-dose
      spiral chest computed tomography (LDCT) provided clinicians with a new tool that
      could be with early diagnosis; however, this also raised significant concerns
      regarding the systematic use of LDCT with its high false-positive rate for benign
      nodules. At this time, there is limited information about the true role of PET
      (positron emission tomography) for early detection of lung cancer. METHODS: We
      used systematic methods, including Preferred Reporting Items for Systematic
      reviews and Meta-Analyses statement, to identify relevant studies, assess study
      eligibility, evaluate study methodological quality, and summarize findings
      regarding diagnostic accuracy and outcome. RESULTS: In total, only seven eligible
      studies were selected from 82 potentially relevant studies. The sensitivity of
      18F-FDG-PET for the detection of T1 lung cancers ranged between 68% and 95%. The
      rate of detection tended to be lower for carcinoid tumors, adenocarcinoma and
      bronchoalveolar cell carcinomas. FDG-PET using SUV (standardized uptake value)
      level can predict the outcome of the screening detected lung cancer. A
      combination of FDG-PET and LDCT may improve screening for lung cancer in high
      risk patients. CONCLUSIONS: PET or PET/CT may be used as a useful tool for early
      detection of lung cancer in high-risk population based on the existing
      information. However, there is still limited information with regards to evidence
      of survival benefits from PET screening in high-risk patients.

PMID- 22404956
TI  - Silicatein: from chemical through enzymatic silica formation, to synthesis of
      biomimetic nanomaterials.
AB  - Silicateins are the enzymes that had been identified in sponges, then sequenced
      and expressed. They are not only the enzymes facilitating biosilica synthesis but
      also function as structure-guiding and structure-forming proteins. The three
      minireviews highlight the principles of silicatein-mediated biosilica formation
      and outline the bionic strategies which might be used for the design and
      fabrication of novel materials.

PMID- 22404957
TI  - Long-term maxillomandibular changes after maxillary distraction osteogenesis in
      growing children with cleft lip with or without palate.
AB  - Objective : To evaluate the long-term maxillomandibular changes after maxillary
      distraction osteogenesis in growing children having cleft lip with or without
      cleft palate. Patients : Eight Japanese patients with cleft lip with or without
      cleft palate aged 9.3 to 13.1 years. Measures : The maxillary and mandibular
      positions before (T0), immediately after (T1), and 1, 3, and 5 years after
      distraction osteogenesis (T2, T3, and T4, respectively) measured on cephalograms
      superimposed at the sella turcica with the Frankfort horizontal plane as the
      horizontal reference. The anterior nasal spine (x, y), pogonion (x), and menton
      (y) were used for linear measurements, and sella turcica-nasion-point A, sella
      turcica-nasion-point B, and point A-nasion-point B angles were used for angular
      measurements. Results : The mean horizontal maxillary advancement (anterior nasal
      spine [x]) was 12.3 mm during T0 to T1, but -2.7, -1.1, and -0.1 mm of the
      posttreatment changes were observed during T1 to T2, T2 to T3, and T3 to T4,
      respectively. Anterior nasal spine (y) shifted 2.3 mm downward during T0 to T1,
      and further downward changes were observed during T1 to T2 and T2 to T3 (P <
      .05). Pogonion (x) did not show distinct changes due to individual variance, but
      menton (y) shifted downward from T1 to T4. Sella turcica-nasion-point A
      significantly decreased during T1 to T2 and T2 to T3 but not during T3-T4. Point
      A-nasion-point B significantly decreased only during T2 to T3, and sella turcica
      nasion-point B did not show any distinct change. Conclusions : There was no
      further maxillary advancement after distraction osteogenesis in the growing
      children with cleft lip with or without cleft palate. Therefore, long-term
      observation and management of occlusion in case of the mandibular growth pattern
      are important.

PMID- 22404958
TI  - Taking responsibility for the early assessment and treatment of patients with
      musculoskeletal pain: a review and critical analysis.
AB  - Musculoskeletal pain is common across all populations and costly in terms of
      impact on the individual and, more generally, on society. In most health-care
      systems, the first person to see the patient with a musculoskeletal problem such
      as back pain is the general practitioner, and access to other professionals such
      as physiotherapists, chiropractors, or osteopaths is still either largely
      controlled by a traditional medical model of referral or left to self-referral by
      the patient. In this paper, we examine the arguments for the general practitioner
      led model and consider the arguments, and underpinning evidence, for
      reconsidering who should take responsibility for the early assessment and
      treatment of patients with musculoskeletal problems.

PMID- 22404960
TI  - A case of Intersexuality in the Parthenogenetic Marmorkrebs (Decapoda: Astacida:
      Cambaridae).
AB  - We describe an intersex specimen of the Marmorkrebs, the only obligate
      parthenogenetic freshwater crayfish with an all-female population. The individual
      was a fully functional female which possessed male-like first pleopods.
      Nevertheless, it reproduced successfully and the offspring were normally
      developed parthenogenetic females, lacking any trace of male traits. The general
      rarity of aberrant sexual traits in freshwater crayfishes, in particular in
      Procambarus, is discussed. We suggest that a dysfunction of the sex determining
      system, which controls the anlagen of the androgenic glands during development,
      caused the partial male-like phenotype of this Marmorkrebs specimen. The
      application of this organism for investigations of sex determination and
      differentiation is recommended.

PMID- 22404959
TI  - Mental health in the slums of Dhaka - a geoepidemiological study.
AB  - BACKGROUND: Urban health is of global concern because the majority of the world's
      population lives in urban areas. Although mental health problems (e.g.
      depression) in developing countries are highly prevalent, such issues are not yet
      adequately addressed in the rapidly urbanising megacities of these countries,
      where a growing number of residents live in slums. Little is known about the
      spectrum of mental well-being in urban slums and only poor knowledge exists on
      health promotive socio-physical environments in these areas. Using a geo
      epidemiological approach, the present study identified factors that contribute to
      the mental well-being in the slums of Dhaka, which currently accommodates an
      estimated population of more than 14 million, including 3.4 million slum
      dwellers. METHODS: The baseline data of a cohort study conducted in early 2009 in
      nine slums of Dhaka were used. Data were collected from 1,938 adults (>= 15
      years). All respondents were geographically marked based on their households
      using global positioning systems (GPS). Very high-resolution land cover
      information was processed in a Geographic Information System (GIS) to obtain
      additional exposure information. We used a factor analysis to reduce the socio
      physical explanatory variables to a fewer set of uncorrelated linear combinations
      of variables. We then regressed these factors on the WHO-5 Well-being Index that
      was used as a proxy for self-rated mental well-being. RESULTS: Mental well-being
      was significantly associated with various factors such as selected features of
      the natural environment, flood risk, sanitation, housing quality, sufficiency and
      durability. We further identified associations with population density, job
      satisfaction, and income generation while controlling for individual factors such
      as age, gender, and diseases. CONCLUSIONS: Factors determining mental well-being
      were related to the socio-physical environment and individual level
      characteristics. Given that mental well-being is associated with physiological
      well-being, our study may provide crucial information for developing better
      health care and disease prevention programmes in slums of Dhaka and other
      comparable settings.

PMID- 22404961
TI  - Immature rat seminal vesicles show histomorphological and ultrastructural
      alterations following treatment with kisspeptin-10.
AB  - BACKGROUND: Degenerative effects of critical regulators of reproduction, the
      kisspeptin peptides, on cellular aspects of sexually immature male gonads are
      known but similar information on accessory sex glands remain elusive. METHODS:
      Prepubertal laboratory rats were injected kisspeptin-10 at three different dosage
      concentrations (10 pg, 1 ng and 1 microgram) for a period of continuous 12 days
      at the rate of two doses per day. Control rats were maintained in parallel. The
      day following the end of the experimental period, seminal vesicles were removed
      and processed for light and electron microscopic examination using the standard
      methods. DNA damage was estimated by DNA ladder assay and DNA fragmentation
      assay. RESULTS: The results demonstrated cellular degeneration. Epithelial cell
      height of seminal vesicles decreased significantly at all doses (P < 0.05).
      Marked decrease in epithelial folds was readily noticeable, while the lumen was
      dilated. Ultrastructural changes were characterized by dilatation of endoplasmic
      reticulum and Golgi complex, heterochromatization of nuclei, invagination of
      nuclear membranes and a decreased number of secretory granules. Percent DNA
      damage to the seminal vesicle was 19.54 +/- 1.98, 38.06 +/- 2.09 and 58.18 +/-
      2.59 at 10 pg, 1 ng and 1 microgram doses respectively. CONCLUSION: The study
      reveals that continuous administration of kisspeptin does not lead to an early
      maturation but instead severe degeneration of sexually immature seminal vesicles.

PMID- 22404962
TI  - ArxA, a new clade of arsenite oxidase within the DMSO reductase family of
      molybdenum oxidoreductases.
AB  - Arsenotrophy, growth coupled to autotrophic arsenite oxidation or arsenate
      respiratory reduction, occurs only in the prokaryotic domain of life. The enzymes
      responsible for arsenotrophy belong to distinct clades within the DMSO reductase
      family of molybdenum-containing oxidoreductases: specifically arsenate
      respiratory reductase, ArrA, and arsenite oxidase, AioA (formerly referred to as
      AroA and AoxB). A new arsenite oxidase clade, ArxA, represented by the
      haloalkaliphilic bacterium Alkalilimnicola ehrlichii strain MLHE-1 was also
      identified in the photosynthetic purple sulfur bacterium Ectothiorhodospira sp.
      strain PHS-1. A draft genome sequence of PHS-1 was completed and an arx operon
      similar to MLHE-1 was identified. Gene expression studies showed that arxA was
      strongly induced with arsenite. Microbial ecology investigation led to the
      identification of additional arxA-like sequences in Mono Lake and Hot Creek
      sediments, both arsenic-rich environments in California. Phylogenetic analyses
      placed these sequences as distinct members of the ArxA clade of arsenite
      oxidases. ArxA-like sequences were also identified in metagenome sequences of
      several alkaline microbial mat environments of Yellowstone National Park hot
      springs. These results suggest that ArxA-type arsenite oxidases appear to be
      widely distributed in the environment presenting an opportunity for further
      investigations of the contribution of Arx-dependent arsenotrophy to the arsenic
      biogeochemical cycle.

PMID- 22404963
TI  - Implementation of the CALM intervention for anxiety disorders: a qualitative
      study.
AB  - BACKGROUND: Investigators recently tested the effectiveness of a collaborative
      care intervention for anxiety disorders: Coordinated Anxiety Learning and
      Management(CALM) []) in 17 primary care clinics around the United States.
      Investigators also conducted a qualitative process evaluation. Key research
      questions were as follows: (1) What were the facilitators/barriers to
      implementing CALM? (2) What were the facilitators/barriers to sustaining CALM
      after the study was completed? METHODS: Key informant interviews were conducted
      with 47 clinic staff members (18 primary care providers, 13 nurses, 8 clinic
      administrators, and 8 clinic staff) and 14 study-trained anxiety clinical
      specialists (ACSs) who coordinated the collaborative care and provided cognitive
      behavioral therapy. The interviews were semistructured and conducted by phone.
      Data were content analyzed with line-by-line analyses leading to the development
      and refinement of themes. RESULTS: Similar themes emerged across stakeholders.
      Important facilitators to implementation included the perception of "low burden"
      to implement, provider satisfaction with the intervention, and frequent provider
      interaction with ACSs. Barriers to implementation included variable provider
      interest in mental health, high rates of part-time providers in clinics, and high
      social stressors of lower socioeconomic-status patients interfering with
      adherence. Key sustainability facilitators were if a clinic had already
      incorporated collaborative care for another disorder and presence of onsite
      mental health staff. The main barrier to sustainability was funding for the ACS.
      CONCLUSIONS: The CALM intervention was relatively easy to incorporate during the
      effectiveness trial, and satisfaction was generally high. Numerous implementation
      and sustainability barriers could limit the reach and impact of widespread
      adoption. Findings should be interpreted with the knowledge that the ACSs in this
      study were provided and trained by the study. Future research should explore
      uptake of CALM and similar interventions without the aid of an effectiveness
      trial.

PMID- 22404964
TI  - The magnesium inhibition and arrested phagosome hypotheses: new perspectives on
      the evolution and ecology of Symbiodinium symbioses.
AB  - Zooxanthella symbioses are arguably the most important ecological interaction on
      coral reefs because they energetically subsidize the entire community, and
      enhance the calcification process that provides structure for all other
      organisms. While we have developed a detailed understanding of the diversity
      among and within the Symbiodinium clades, we currently lack a mechanistic
      explanation for which factors favoured zooxanthella invasion of the intracellular
      habitat in heterotrophic hosts, and for what molecular mechanisms permit
      residence within the cell. We propose two hypotheses that explain important
      evolutionary and ecological features of zooxanthella symbioses. The magnesium
      inhibition hypothesis (MIH) states that increases in the Mg/Ca ratio in sea water
      that occurred over the last 100 million years created a situation where Mg(2+)
      inhibited Ca(2+) transport to zooxanthellae. The MIH predicts, among other
      things, that the intracellular niche was invaded as a response to this abiotic
      stressor. The arrested phagosome hypothesis (APH) states that Symbiodinium spp.
      mimic host cell endosomal digestive machinery via the symbiosome to appear like
      digesting prey through perpetual release of zooxanthella-derived compounds. The
      APH represents a subtle but important distinction from previous hypotheses
      regarding interactions between symbiont and host at the cellular level. The APH
      predicts that symbionts tune rates of material release to match expectations of
      host cellular machinery. An outcome of the APH is that intra-host residence time
      becomes a vital parameter to consider. Both hypotheses shift control of the
      symbiosis away from the host, and instead focus attention on the niche
      requirements of Symbiodinium spp.

PMID- 22404965
TI  - A dose-finding study with a novel water-soluble formulation of paclitaxel for the
      treatment of malignant high-grade solid tumours in dogs.
AB  - A new formulation of water-soluble paclitaxel (Paccal(r) Vet) has been developed
      for canine cancer patients, without the need for pre-medication (traditionally
      required in non-water-soluble paclitaxel formulations). The objective of the
      study was to determine a clinically safe and efficacious dose of Paccal Vet and
      to estimate progression-free and overall survival and to evaluate single-dose
      pharmacokinetics in tumour-bearing dogs. A positive risk:benefit ratio was
      established for Paccal Vet administered at 150 mg m(-2) intravenous (IV) for
      three or more treatment cycles. Preliminary efficacy was demonstrated by best
      objective response rate (86%), median time to response (14 days) and median
      progression-free survival (131 days). Paccal Vet was associated with expected
      adverse events (AE) (e.g. myelosuppression), however the majority were transient,
      clinically silent and manageable. This is the first clinical report of a water
      soluble formulation of paclitaxel suggesting successful administration and being
      safely used without pre-medication in dogs.

PMID- 22404966
TI  - The gpsX gene encoding a glycosyltransferase is important for polysaccharide
      production and required for full virulence in Xanthomonas citri subsp. citri.
AB  - BACKGROUND: The Gram-negative bacterium Xanthomonas citri subsp. citri (Xac)
      causes citrus canker, one of the most destructive diseases of citrus worldwide.
      In our previous work, a transposon mutant of Xac strain 306 with an insertion in
      the XAC3110 locus was isolated in a screening that aimed at identifying genes
      related to biofilm formation. The XAC3110 locus was named as bdp24 for biofilm
      defective phenotype and the mutant was observed to be affected in extracellular
      polysaccharide (EPS) and lipopolysaccharide (LPS) biosynthesis and cell motility.
      In this study, we further characterized the bdp24 (XAC3110) gene (designated as
      gpsX) using genetic complementation assays and expanded the knowledge about the
      function of the gpsX gene in Xac pathogenesis by investigating the roles of gpsX
      in EPS and LPS production, cell motility, biofilm formation on host leaves,
      stress tolerance, growth in planta, and host virulence of the citrus canker
      bacterium. RESULTS: The gpsX gene encodes a putative glycosyltransferase, which
      is highly conserved in the sequenced strains of Xanthomonas. Mutation of gpsX
      resulted in a significant reduction of the amount of EPS and loss of two LPS
      bands visualized on sodium dodecylsulphate- polyacrylamide gels. Biofilm assays
      revealed that the gpsX mutation affected biofilm formation by Xac on abiotic and
      biotic surfaces. The gpsX mutant showed delayed bacterial growth and caused
      reduced development of disease symptoms in susceptible citrus leaves. The gpsX
      mutant was more sensitive than the wild-type strain to various stresses,
      including the H(2)O(2) oxidative stress. The mutant also showed attenuated
      ability in cell motility but not in flagellar formation. Quantitative reverse
      transcription-PCR assays indicated that mutation of gpsX did not affect the
      expression of virulence genes such as pthA in Xac strain 306. The affected
      phenotypes of the gpsX mutant could be complemented to wild-type levels by the
      intact gpsX gene. CONCLUSIONS: Taken together, our data confirm that the gpsX
      gene is involved in EPS and LPS synthesis and biofilm formation in Xac and
      suggest that the gpsX gene contributes to the adaptation of Xac to the host
      microenvironments at early stage of infection and thus is required for full
      virulence on host plants.

PMID- 22404967
TI  - The Ngorongoro Volcanic Highland and its relationships to volcanic deposits at
      Olduvai Gorge and East African Rift volcanism.
AB  - The Ngorongoro Volcanic Highland (NVH), situated adjacent and to the east of
      Olduvai Gorge in northern Tanzania, is the source of the immense quantities of
      lava, ignimbrite, air fall ash, and volcaniclastic debris that occur interbedded
      in the Plio-Pleistocene sedimentary deposits in the Laetoli and Olduvai areas.
      These volcanics have proven crucial to unraveling stratigraphic correlations, the
      age of these successions, the archaeological and paleontological remains, as well
      as the source materials from which the bulk of the stone tools were manufactured.
      The NVH towers some 2,000 m above the Olduvai and Laetoli landscapes, affecting
      local climate, run-off, and providing varying elevation - climate controlled
      ecosystem, habitats, and riparian corridors extending into the Olduvai and
      Laetoli lowlands. The NVH also plays a crucial role in addressing the genesis and
      history of East African Rift (EAR) magmatism in northern Tanzania. In this
      contribution, we provide age and petrochemical compositions of the major NVH
      centers: Lemagurut, basalt to benmorite, 2.4-2.2 Ma; Satiman, tephrite to
      phonolite, 4.6-3.5 Ma; Oldeani, basalt to trachyandesite, 1.6-1.5 Ma; Ngorongoro,
      basalt to rhyolite, 2.3-2.0 Ma; Olmoti, basalt to trachyte, 2.0-1.8 Ma; Embagai,
      nephelinite to phonolite, 1.2-0.6 Ma; and Engelosin, phonolite, 3-2.7 Ma. We then
      discuss how these correlate in time and composition with volcanics preserved at
      Olduvai Gorge. Finally, we place this into context with our current understanding
      as to the eruptive history of the NVH and relationship to East African Rift
      volcanism.

PMID- 22404968
TI  - PTP1B and TCPTP--nonredundant phosphatases in insulin signaling and glucose
      homeostasis.
AB  - Insulin resistance is a key pathological feature of type 2 diabetes and is
      characterized by defects in signaling by the insulin receptor (IR) protein
      tyrosine kinase. The inhibition of protein tyrosine phosphatases (PTPs) that
      antagonize IR signaling may provide a means for enhancing the insulin response
      and alleviating insulin resistance. The prototypic phosphotyrosine-specific
      phosphatase PTP1B dephosphorylates the IR and attenuates insulin signaling in
      muscle and liver. Mice that are deficient for PTP1B exhibit improved glucose
      homeostasis in diet and genetic models of insulin resistance and type 2 diabetes.
      The phosphatase TCPTP shares 72% catalytic domain sequence identity with PTP1B
      and has also been implicated in IR regulation. Despite their high degree of
      similarity, PTP1B and TCPTP act together in vitro and in vivo to regulate insulin
      signaling and glucose homeostasis. This review highlights their capacity to act
      specifically and nonredundantly in cellular signaling, describes their roles in
      IR regulation and glucose homeostasis, and discusses their potential as drug
      targets for the enhancement of IR phosphorylation and insulin sensitivity in type
      2 diabetes.

PMID- 22404970
TI  - Differential biomagnification of PCB, PBDE, Hg and Radiocesium in the food web of
      the European hake from the NW Mediterranean.
AB  - Consumption of marine organisms represents one of the main exposure sources of
      contaminants for human populations. To obtain a global view of the contamination
      in commercial fish in the NW Mediterranean Sea, we analysed four types of
      priority contaminants (PCBs, PBDEs, Hg and (137)Cs) in the European hake,
      Merluccius merluccius, from the Gulf of Lions in relation with organism's trophic
      level (delta(15)N). All contaminants presented a significant increase in
      concentration in hake muscle with trophic level. However, obvious differences
      between contaminants were evidenced. Biomagnification factors (BMF and FWMF)
      along the hake food web were higher for Hg and CB-153 than for BDE-47 and
      (137)Cs, and increase in contaminant concentration with trophic level occurred at
      different rates depending on contaminants. Such differences of biomagnification
      patterns can be related to physico-chemical properties of the different
      contaminants.

PMID- 22404969
TI  - Is IL-6 an appropriate target to treat spondyloarthritis patients refractory to
      anti-TNF therapy? A multicentre retrospective observational study.
AB  - INTRODUCTION: The aim of this study was to evaluate, under real-life conditions,
      the safety and efficacy of tocilizumab in patients having failed anti-TNFalpha
      therapy for spondyloarthritis. METHODS: French rheumatologists and internal
      medicine practitioners registered on the Club Rhumatismes et Inflammations
      website were asked to report on patients given tocilizumab (4 or 8 mg/kg) to
      treat active disease meeting Assessment of SpondyloArthritis International
      Society (ASAS) criteria for axial or peripheral spondyloarthritis, after anti
      TNFalpha treatment failure. Safety and efficacy after 3 and 6 months were
      assessed retrospectively using standardised questionnaires. RESULTS: Data were
      obtained for 21 patients, 13 with axial spondyloarthritis (46% men; median age,
      42 years; disease duration, 11 years; HLA-B27-positive, 92.3%) and eight with
      peripheral spondyloarthritis (25% men; median age, 40 years; disease duration, 10
      years; HLA-B27-positive, 62.5%). No patients with axial disease had at least a 20
      mm decrease in the BASDAI, nor a BASDAI50 response or major ASAS-endorsed disease
      activity score improvements after 3 or 6 months; an ASAS-endorsed disease
      activity score clinically important improvement was noted at month 3 in five of
      13 patients and at month 6 in one of four patients. A good DAS28 response was
      achieved in four patients with peripheral disease, including one in EULAR
      remission at month 3. Four patients were still taking tocilizumab at month 6,
      including one in EULAR remission and one with a good DAS28 response. Tocilizumab
      was well tolerated, with no serious adverse events. Initially elevated acute
      phase reactants declined during tocilizumab therapy. CONCLUSION: In patients
      having failed anti-TNFalpha therapy, tocilizumab decreased acute-phase reactants
      but failed to substantially improve axial spondyloarthritis and was
      inconsistently effective in peripheral spondyloarthritis.

PMID- 22404971
TI  - The effects of an intervention program for promoting interorganizational network
      building between multidisciplinary agencies and community-based organizations: a
      cluster trial in Japan.
AB  - BACKGROUND: Strengthening interorganizational relationships in the community has
      become an increasingly valued strategy for improving public health in recent
      years. However, no intervention strategy to foster an interorganizational network
      in the community has yet been devised. The purpose of this study was to examine
      the effects on members of an organization of an intervention program designed to
      promote interorganizational network building between multidisciplinary agencies
      and community-based organizations (CBOs). METHODS: The program was conducted in
      Setagaya and Suginami wards, Tokyo, Japan, for staff of community comprehensive
      support centers (CCSCs), which are multidisciplinary organizations responsible
      for the support of the elderly. A cluster non-randomized design with a CCSC as a
      cluster unit (N = 47) was used. The intervention group comprised 20 centers and
      the control group 27 centers. Those 27 centers declined to participate in program
      sessions, but did participate through completing pre- and post-intervention
      surveys. In total, 158 staff members were eligible to participate in this study,
      73 from the intervention group and 85 from the control group. Of the 73 members
      in the intervention group, 19 participated in the monthly program sessions, over
      a period of 10 months. Attendees participated in group discussions during the
      sessions. The effects of the intervention were examined by comparing three groups
      (attendees and non-attendees of the program from the intervention group, and the
      control group) and between two groups (intervention group and control group).
      RESULTS: We found no significant difference in any outcome between the
      intervention group and the control group. However, among the three groups, a
      significant effect was found in the recognition of knowledge and skills for
      building networks with CBOs. Recognition of knowledge and skills increased
      significantly among the attendees compared to non-attendees in the intervention
      group and the control group. In addition, there was a significant effect,
      particularly on those with relatively low baseline scores, for the recognition of
      knowledge and skills. CONCLUSIONS: The tested intervention proved effective for
      attendees regarding their recognition of knowledge and skills for promoting
      interorganizational network building with CBOs.

PMID- 22404972
TI  - Differential p38-dependent signalling in response to cellular stress and
      mitogenic stimulation in fibroblasts.
AB  - p38 MAP kinase is known to be activated by cellular stress finally leading to
      cell cycle arrest or apoptosis. Furthermore, a tumour suppressor role of p38 MAPK
      has been proposed. In contrast, a requirement of p38 for proliferation has also
      been described. To clarify this paradox, we investigated stress- and mitogen
      induced p38 signalling in the same cell type using fibroblasts. We demonstrate
      that - in the same cell line - p38 is activated by mitogens or cellular stress,
      but p38-dependent signalling is different. Exposure to cellular stress, such as
      anisomycin, leads to a strong and persistent p38 activation independent of
      GTPases. As a result, MK2 and downstream the transcription factor CREB are
      phosphorylated. In contrast, mitogenic stimulation results in a weaker and
      transient p38 activation, which upstream involves small GTPases and is required
      for cyclin D1 induction. Consequently, the retinoblastoma protein is
      phosphorylated and allows G1/S transition. Our data suggest a dual role of p38
      and indicate that the level and/or duration of p38 activation determines the
      cellular response, i.e either proliferation or cell cycle arrest.

PMID- 22404973
TI  - Development of five new melanoma low passage cell lines representing the clinical
      and genetic profile of their tumors of origin.

PMID- 22404974
TI  - Ex-vivo porcine organs with a circulation pump are effective for teaching
      hemostatic skills.
AB  - Surgical residents have insufficient opportunites to learn basic hemostatic
      skills from clinical experience alone. We designed an ex-vivo training system
      using porcine organs and a circulation pump to teach hemostatic skills. Residents
      were surveyed before and after the training and showed significant improvement in
      their self-confidence (1.83 +/- 1.05 vs 3.33 +/- 0.87, P < 0.01) on a 5 point
      Likert scale. This training may be effective to educate residents in basic
      hemostatic skills.

PMID- 22404976
TI  - Acute phase proteins in patients with cirrhosis.

PMID- 22404977
TI  - Can transient elastography be used for the management of chronic hepatitis B
      patients?

PMID- 22404978
TI  - Bet-hedging--a triple trade-off between means, variances and correlations.
AB  - In unpredictably varying environments, strategies that have a reduced variance in
      fitness can invade a population consisting of individuals that on average do
      better. Such strategies 'hedge their evolutionary bets' against the variability
      of the environment. The idea of bet-hedging arises from the fact that appropriate
      measure of long-term fitness is sensitive to variance, leading to the potential
      for strategies with a reduced mean fitness to invade and increase in frequency.
      Our aim is to review the conceptual foundation of bet-hedging as a mechanism that
      influences short- and long-term evolutionary processes. We do so by presenting a
      general model showing how evolutionary changes are affected by variance in
      fitness and how genotypic variance in fitness can be separated into variance in
      fitness at the level of the individuals and correlations in fitness among them.
      By breaking down genotypic fitness variance in this way the traditional divisions
      between conservative and diversified strategies are more easily intuited, and it
      is also shown that this division can be considered a false dichotomy, and is
      better viewed as two extreme points on a continuum. The model also sheds light on
      the ideas of within- and between-generation bet-hedging, which can also be
      generalized to be seen as two ends of a different continuum. We use a simple
      example to illustrate the virtues of our general model, as well as discuss the
      implications for systems where bet-hedging has been invoked as an explanation.

PMID- 22404979
TI  - Human islets express a marked proinflammatory molecular signature prior to
      transplantation.
AB  - In the context of islet transplantation, experimental models show that induction
      of islet intrinsic NF-kappaB-dependent proinflammatory genes can contribute to
      islet graft rejection. Isolation of human islets triggers activation of the NF
      kappaB and mitogen-activated kinase (MAPK)  stress response pathways. However,
      the downstream NF-kappaB target genes induced in human islets during the
      isolation process are poorly described. Therefore, in this study, using
      microarray, bioinformatic, and RTqPCR approaches, we determined the pattern of
      genes expressed by a set of 14  human islet preparations. We found that isolated
      human islets express a panel of genes reminiscent of cells undergoing a marked NF
      kappaB-dependent proinflammatory response. Expressed genes included matrix
      metallopeptidase 1 (MMP1) and fibronectin 1 (FN1), factors involved in tissue
      remodeling,  adhesion, and cell migration; inflammatory cytokines IL-1beta and IL
      8; genes regulating cell survival including A20 and ATF3; and notably high
      expression of a set of chemokines that would favor neutrophil and monocyte
      recruitment including CXCL2, CCL2, CXCL12, CXCL1, CXCL6, and CCL28. Of  note, the
      inflammatory profile of isolated human islets was maintained after
      transplantation into RAG(-/-) recipients. Thus, human islets can provide a
      reservoir of NF-kappaB-dependent inflammatory factors that have the potential to
      contribute to the anti-islet-graft immune response.  To test this hypothesis, we
      extracted rodent islets under optimal conditions, forced activation of NF-kappaB,
      and transplanted them into allogenic recipients. These NF-kappaB activated islets
      not only expressed the same chemokine profile observed in human islets but also
      struggled to maintain  normoglycemia posttransplantation. Further, NF-kappaB
      activated islets were rejected with a faster tempo as compared to non-NF-kappaB
      activated rodent islets. Thus, isolated human islets can make cell autonomous
      contributions to the ensuing allograft response by elaborating inflammatory 
      factors that contribute to their own demise. These data highlight the potential
      importance of islet intrinsic proinflammatory responses as targets for
      therapeutic intervention.

PMID- 22404980
TI  - Potential impact of fertilization practices on human dietary intake of dioxins in
      Belgium.
AB  - Dioxins can enter the food chain at any stage, including crop fertilization.
      Therefore, we developed a simple method for estimating the introduction of
      dioxins in the food chain according to various fertilization practices. Using
      dioxin's contamination data taken from the literature, we estimated that
      fertilization accounts for approximately 20% of the dioxin inputs on agricultural
      soils at country scale. For the estimations at the field scale, 6 fertilization
      scenarios were considered: sludge, compost, digestate, manure, mineral
      fertilizers, and a common fertilization scenario that corresponds to an average
      situation in Belgium and combines mineral and organic fertilizers. According to
      our first estimations, mineral fertilizers, common fertilization practices or
      manure bring less than 1 ng TEQ/m2 while atmospheric deposition or digestate
      bring between 1 and 3 ng TEQ/m2 and sludge or compost bring more than 3 ng
      TEQ/m2. The use of solid fertilizers could potentially increase the dioxin levels
      in the 30 cm agricultural soil layer by 0 to ~1.5% per year (up to ~9% for the 5
      cm thick surface layer). For animals, the increase in dioxin ingestion linked to
      the fertilization practices is lower than 1% for most scenarios with the
      exception of the compost scenario. Increases in human dietary intake of dioxin
      are estimated to be lower than 1% for conventional rearing methods (i.e. grazing
      animals are reared outdoor while pigs and poultry are reared indoor). Spraying
      liquid fertilizers on meadows and fodder crops, even if very limited in practice,
      deserves much more attention because this application method could theoretically
      lead to higher dioxin's intake by livestock (from 6 to ~300%). Considering an
      average half-life of dioxins in soils of 13 years, it appears that the risks of
      accumulation in soils and in the food chain are negligible for the various
      fertilization scenarios.

PMID- 22404981
TI  - Estimation of community-wide drugs use via stereoselective profiling of sewage.
AB  - This paper explores possibilities of applying enantiomeric profiling to solving
      problems related to estimation of drugs usage in communities via the sewage
      epidemiology approach: for the identification of whether drug residue results
      from consumption of illicit drug or metabolism of other drugs, verification of
      potency of used drugs and monitoring of changing patterns of drugs abuse. Due to
      the very complex nature of wastewater used in sewage epidemiology, which comes
      from the whole community rather than one individual, verification of the above is
      challenging but vital in accurate estimations of drugs abuse as well as providing
      comprehensive information regarding drug abuse trends. The results of this study
      indicated that amphetamine in raw wastewater was enriched with R(-)-enantiomer
      due to its abuse as racemate. Methamphetamine was found to be racemic or to be
      enriched with S(+)-enantiomer. MDMA was enriched with R(-)-MDMA, which was to be
      expected as MDMA is abused as racemate. MDA was enriched with S(+)-enantiomer,
      which suggests that its presence might be associated with MDMA abuse and not
      intentional MDA use. Out of the four possible isomers of ephedrine only natural
      1R,2S(-)-ephedrine and 1S,2S(+)-pseudoephedrine were detected in raw wastewater
      and their diastereomeric fractions were found to be season dependent with higher
      contribution from 1S,2S(+)-pseudoephedrine over winter months and an enrichment
      with 1R,2S(-)-ephedrine during the spring and summer months. These findings were
      accompanied by a decrease of cumulative concentration of ephedrines throughout
      the sampling campaign between February and August. This is a very important
      finding indicating that non-enantioselective measurement of ephedrine
      concentrations cannot be a reliable indicator of actual potency of ephedrines
      used.

PMID- 22404982
TI  - Significant differences in the cell-wall mannans from three Candida glabrata
      strains correlate with antifungal drug sensitivity.
AB  - Candida glabrata is often the second or third most common cause of candidiasis
      after Candida albicans. C. glabrata infections are difficult to treat, often
      resistant to many azole antifungal agents and are associated with a high
      mortality rate in compromised patients. We determined the antigenic structure of
      the cell-wall mannoproteins from three C. glabrata strains, NBRC 0005, NBRC 0622
      and NBRC 103857. (1)H NMR and methylation analyses of the acetolysis products of
      these mannoproteins showed a significant difference in the amount of the beta-1,2
      linked mannose residue and side-chain structure. The C. glabrata NBRC 103857
      strain contained up to the triose side chains and the nonreducing terminal of the
      triose was predominantly the beta-1,2-linked mannose residue. By contrast, the
      mannans of the two former strains possessed up to the tetraose side chains and
      the amount of the beta-1,2-linked mannose residue was very low. Larger
      oligosaccharides than tetraose in the acetolysis products of these mannans were
      identified as incomplete cleavage fragments by analyzing methylation, (1)H NMR
      spectra and the alpha1-2,3 mannosidase degradation reaction. Resistance to the
      antifungal drugs itraconazole and micafungin was significantly different in these
      strains. Interestingly, the NBRC 103857 strain, which involved a large amount of
      the beta-1,2-linked mannose residues, exhibited significant sensitivity to these
      antifungal drugs.

PMID- 22404983
TI  - A combined study using ligand-based design, synthesis, and pharmacological
      evaluation of analogues of the acetaminophen ortho-regioisomer with potent
      analgesic activity.
AB  - A ligand-based drug design study was performed to acetaminophen regioisomers as
      analgesic candidates employing quantum chemical calculations at the DFT/B3LYP
      level of theory and the 6-31G* basis set. To do so, many molecular descriptors
      were used such as highest occupied molecular orbital, ionization potential, H-O
      bond dissociation energies, and spin densities, which might be related to quench
      reactivity of the tyrosyl radical to give N-acetyl-p-benzosemiquinone-imine
      through an initial electron withdrawing or hydrogen atom abstraction. Based on
      this in silico work, the most promising molecule, orthobenzamol, was synthesized
      and tested. The results expected from the theoretical prediction were confirmed
      in vivo using mouse models of nociception such as writhing, paw licking, and hot
      plate tests. All biological results suggested an antinociceptive activity
      mediated by opioid receptors. Furthermore, at 90 and 120 min, this new compound
      had an effect that was comparable to morphine, the standard drug for this test.
      Finally, the pharmacophore model is discussed according to the electronic
      properties derived from quantum chemistry calculations.

PMID- 22404984
TI  - Protein kinase CK2 localizes to sites of DNA double-strand break regulating the
      cellular response to DNA damage.
AB  - BACKGROUND: The DNA-dependent protein kinase (DNA-PK) is a nuclear complex
      composed of a large catalytic subunit (DNA-PKcs) and a heterodimeric DNA
      targeting subunit Ku. DNA-PK is a major component of the non-homologous end
      joining (NHEJ) repair mechanism, which is activated in the presence of DNA double
      strand breaks induced by ionizing radiation, reactive oxygen species and
      radiomimetic drugs. We have recently reported that down-regulation of protein
      kinase CK2 by siRNA interference results in enhanced cell death specifically in
      DNA-PKcs-proficient human glioblastoma cells, and this event is accompanied by
      decreased autophosphorylation of DNA-PKcs at S2056 and delayed repair of DNA
      double-strand breaks. RESULTS: In the present study, we show that CK2 co
      localizes with phosphorylated histone H2AX to sites of DNA damage and while CK2
      gene knockdown is associated with delayed DNA damage repair, its overexpression
      accelerates this process. We report for the first time evidence that lack of CK2
      destabilizes the interaction of DNA-PKcs with DNA and with Ku80 at sites of
      genetic lesions. Furthermore, we show that CK2 regulates the phosphorylation
      levels of DNA-PKcs only in response to direct induction of DNA double-strand
      breaks. CONCLUSIONS: Taken together, these results strongly indicate that CK2
      plays a prominent role in NHEJ by facilitating and/or stabilizing the binding of
      DNA-PKcs and, possibly other repair proteins, to the DNA ends contributing to
      efficient DNA damage repair in mammalian cells.

PMID- 22404986
TI  - Developing a nanoparticle test for prostate cancer scoring.
AB  - BACKGROUND: Over-diagnosis and treatment of prostate cancer has been a major
      problem in prostate cancer care and management. Currently the most relevant
      prognostic factor to predict a patient's risk of death due to prostate cancer is
      the Gleason score of the biopsied tissue samples. However, pathological analysis
      is subjective, and the Gleason score is only a qualitative estimate of the cancer
      malignancy. Molecular biomarkers and diagnostic tests that can accurately predict
      prostate tumor aggressiveness are rather limited. METHOD: We report here for the
      first time the development of a nanoparticle test that not only can distinguish
      prostate cancer from normal and benign conditions, but also has the potential to
      predict the aggressiveness of prostate cancer quantitatively. To conduct the
      test, a prostate tissue lysate sample is spiked into a blood serum or human IgG
      solution and the spiked sample is incubated with a citrate-protected gold
      nanoparticle solution. IgG is known to adsorb to citrate-protected gold
      nanoparticles to form a "protein corona" on the nanoparticle surface. From this
      study, we discovered that certain tumor-specific molecules can interact with IgG
      and change the adsorption behavior of IgG to the gold nanoparticles. This change
      is reflected in the nanoparticle size of the assay solution and detected by a
      dynamic light scattering technique. Assay data were analyzed by one-way ANOVA for
      multiple variant analysis, and using the Student t-test or nonparametric Mann
      Whitney U-tests for pairwise analyses. RESULTS: An inverse, quantitative
      correlation of the average nanoparticle size of the assay solution with tumor
      status and histological diagnostic grading was observed from the nanoparticle
      test. IgG solutions spiked with prostate tumor tissue exhibit significantly
      smaller nanoparticle size than the solutions spiked with normal and benign
      tissues. The higher grade the tumor is, the smaller the nanoparticle size is. The
      test particularly revealed large differences among the intermediate Grade 2
      tumors, and suggested the need to treat them differently. CONCLUSION: Development
      of a new nanoparticle test may provide a quantitative measure of the prostate
      cancer aggressiveness. If validated in a larger study of patients with prostate
      cancer, this test could become a new diagnostic tool in conjunction with Gleason
      Score pathology diagnostics to better distinguish aggressive cancer from indolent
      tumor.

PMID- 22404985
TI  - The anti-CD74 humanized monoclonal antibody, milatuzumab, which targets the
      invariant chain of MHC II complexes, alters B-cell proliferation, migration, and
      adhesion molecule expression.
AB  - INTRODUCTION: Targeting CD74 as the invariant chain of major histocompatibility
      complexes (MHC) became possible by the availability of a specific humanized
      monoclonal antibody, milatuzumab, which is under investigation in patients with
      hematological neoplasms. CD74 has been reported to regulate chemo-attractant
      migration of macrophages and dendritic cells, while the role of CD74 on
      peripheral naive and memory B cells also expressing CD74 remains unknown.
      Therefore, the current study addressed the influence of milatuzumab on B-cell
      proliferation, chemo-attractant migration, and adhesion molecule expression.
      METHODS: Surface expression of CD74 on CD27- naive and CD27+ memory B cells as
      well as other peripheral blood mononuclear cells (PBMCs) obtained from normals,
      including the co-expression of CD44, CXCR4, and the adhesion molecules CD62L,
      beta7-integrin, beta1-integrin and CD9 were studied after binding of milatuzumab
      using multicolor flow cytometry. The influence of the antibody on B-cell
      proliferation and migration was analyzed in vitro in detail. RESULTS: In addition
      to monocytes, milatuzumab also specifically bound to human peripheral B cells,
      with a higher intensity on CD27+ memory versus CD27- naive B cells. The antibody
      reduced B-cell proliferation significantly but moderately, induced enhanced
      spontaneous and CXCL12-dependent migration together with changes in the
      expression of adhesion molecules, CD44, beta7-integrin and CD62L, mainly of CD27-
      naive B cells. This was independent of macrophage migration-inhibitory factor as
      a ligand of CD74/CD44 complexes. CONCLUSIONS: Milatuzumab leads to modestly
      reduced proliferation, alterations in migration, and adhesion molecule expression
      preferentially of CD27- naive B cells. It thus may be a candidate antibody for
      the autoimmune disease therapy by modifying B cell functions.

PMID- 22404987
TI  - Wound Management Innovation Cooperative Research Centre - a new model for inter
      disciplinary wound research.

PMID- 22404991
TI  - [Unsuspected pulmonary thromboembolism in the Emergency Department].
AB  - BACKGROUND AND OBJECTIVES: Pulmonary embolism (PE) is a disease that sometimes
      has a significant delay in diagnosis. This situation may lead to an increase in
      morbidity and mortality in patients who have it. The aim of our study has been to
      define the clinical profile of patients with unsuspected PE in the emergency
      department and the factors that influence the delayed diagnosis. PATIENTS AND
      METHODS: A total of 148 patients admitted with diagnosis of PE confirmed by CT
      (n=133) or by high-probability ventilation-perfusion scintigraphy scan (n=15)
      were retrospectively analyzed. They were divided into two groups: those with
      unsuspected disease in the emergency department (USPE) and those who it was
      suspected (SPE). Baseline characteristics of the patients, risk factors, signs
      and symptoms in the emergency department, complementary test, days of
      hospitalization and mortality were studied. RESULTS: The USPE was found in 63/148
      patients (42.6%) in the emergency department. Dyspnea and chest pain were the
      most frequent clinical manifestations of this disease, this being more commonly
      identified in the SPE group than in the USPE group, with significant differences
      (OR=0.4 [0.2-0.9] for dyspnea and OR=0.3 [0.2-0.7] for chest pain). However,
      However, the presence of thrombocytopenia (OR=3.4 [1.1-10.2], P<.05), normal
      electrocardiogram (EC) (OR=3.4 [1.1-10.2], P<.05), and localization of PE in
      right lung (OR=4.7 [2-11.3], P<.001) were risk factors for not suspect it. Days
      of hospitalization, days of symptoms and mortality were not statistically
      different between groups. CONCLUSIONS: According to the results, the proportion
      of unsuspected PE in the emergency department was high (close to 40%). The
      presence of dyspnea and chest pain was associated to suspicion of SPE. On the
      contrary, the presence of thrombocytopenia, normal EC and right localization of
      PE were associated to the non-suspicion of SPE in the emergency department.

PMID- 22404992
TI  - Chronic obstructive pulmonary disease. Are the times changing?
AB  - Chronic obstructive pulmonary disease (COPD) is one of the most prevalent
      diseases and a major cause of morbidity and mortality in Spain. Currently, COPD
      is considered a treatable disease with an inflammatory origin that is frequently
      associated with other diseases. The prevalence of comorbidity is clearly
      increased in patients with COPD, irrespective of other confounding variables such
      as smoking. Current treatments have been proven to slow the loss of lung
      function, decrease the number of exacerbations and improve health-related quality
      of life and survival. New advances regarding the classics and more recent
      phenotypes such as patients with frequent exacerbations or COPD with associated
      comorbidity should allow for more individualized treatment while advances in
      genetic research and inflammatory mechanisms of the disease will help us to
      increase our knowledge of the disease and the development of new treatments.

PMID- 22404993
TI  - Pretransplant donor-specific HLA class-I and -II antibodies are associated with
      an increased risk for kidney graft failure.
AB  - Pretransplant risk assessment of graft failure is important for donor selection
      and choice of immunosuppressive treatment. We examined the relation between
      kidney graft failure and presence of IgG donor specific HLA antibodies (DSA) or
      C1q-fixing DSA, detected by single antigen bead array (SAB) in pretransplant sera
      from 837 transplantations. IgG-DSA were found in 290 (35%) sera, whereas only 30
      (4%) sera had C1q-fixing DSA. Patients with both class-I plus -II DSA had a 10 yr
      graft survival of 30% versus 72% in patients without HLA antibodies (p < 0.001).
      No significant difference was observed in graft survival between patients with or
      without C1q-fixing DSA. Direct comparison of both assays showed that high mean
      fluorescence intensity values on the pan-IgG SAB assay are generally related to
      C1q-fixation. We conclude that the presence of class-I plus -II IgG DSA as
      detected by SAB in pretransplant sera of crossmatch negative kidney recipients is
      indicative for an increased risk for graft failure, whereas the clinical
      significance of C1q-fixing IgG-DSA could not be assessed due to their low
      prevalence.

PMID- 22404994
TI  - UBAP1: a new ESCRT member joins the cl_Ub.
AB  - The ESCRTs play multiple roles within the cell, including degradation of
      ubiquitinated membrane proteins by sorting them into multivesicular bodies
      (MVBs). Two recent studies provide structural and functional insights into how
      the newly identified ESCRT-I component UBAP1 dedicates ESCRT-I function for
      sorting ubiquitinated proteins at the MVB (Agromayor et al., 2012 [this issue of
      Structure]; Stefani et al., 2011).

PMID- 22404995
TI  - Ob-stopping obesity, metabolic and immune-mediated disorders.
AB  - Despite its physiological importance, no part of human leptin receptor (ObR) has
      been structurally characterized before. In this issue of Structure, Carpenter et
      al. report the crystal structure of the leptin-binding domain of human ObR in
      complex with the Fab fragment of an ObR-blocking monoclonal antibody (9F8 mAb).

PMID- 22404996
TI  - The 19S cap puzzle: a new jigsaw piece.
AB  - After elucidation of the atomic details of 20S proteasomes, current research
      focuses on the regulatory 19S particle. In this issue of Structure, He et al.
      present the crystal structure of Rpn2 and use electron microscopy to examine
      differences between Rpn2 and Rpn1.

PMID- 22404997
TI  - Cas protein Cmr2 full of surprises.
AB  - The Cmr complex carries out target RNA degradation in organisms possessing the
      CRISPR-Cas system. In this issue of Structure, Cocozaki et al. present the
      crystal structure of Cmr2, providing insight into the architecture of the Cmr
      complex.

PMID- 22404998
TI  - The Protein Data Bank at 40: reflecting on the past to prepare for the future.
AB  - A symposium celebrating the 40th anniversary of the Protein Data Bank archive
      (PDB), organized by the Worldwide Protein Data Bank, was held at Cold Spring
      Harbor Laboratory (CSHL) October 28-30, 2011. PDB40's distinguished speakers
      highlighted four decades of innovation in structural biology, from the early era
      of structural determination to future directions for the field.

PMID- 22404999
TI  - Structural and functional discussion of the tetra-trico-peptide repeat, a protein
      interaction module.
AB  - Tetra-trico-peptide repeat (TPR) domains are found in numerous proteins, where
      they serve as interaction modules and multiprotein complex mediators. TPRs can be
      found in all kingdoms of life and regulate diverse biological processes, such as
      organelle targeting and protein import, vesicle fusion, and biomineralization.
      This review considers the structural features of TPR domains that permit the
      great ligand-binding diversity of this motif, given that TPR-interacting partners
      display variations in both sequence and secondary structure. In addition, tools
      for predicting TPR-interacting partners are discussed, as are the abilities of
      TPR domains to serve as protein-protein interaction scaffolds in biotechnology
      and therapeutics.

PMID- 22405000
TI  - Improved visualization of vertebrate nuclear pore complexes by field emission
      scanning electron microscopy.
AB  - Field emission scanning electron microscopy (FESEM) can provide high-resolution
      three-dimensional surface imaging of many biological structures, including
      nuclear envelopes and nuclear pore complexes (NPCs). For this purpose, it is
      important to preserve NPCs as close as possible to their native morphology,
      embedded in undamaged nuclear membranes. We present optimized methodologies for
      FESEM imaging in a cell-free reconstitution system and for the direct
      visualization of mammalian cell nuclei. The use of anchored chromatin templates
      in the cell-free system is particularly advantageous for imaging fragile
      intermediates inhibited at early stages of assembly. Our new method for exposing
      the surface of mammalian nuclei results in an unprecedented quality of NPC
      images, avoiding detergent-induced and physical damage. These new methodologies
      pave the way for the combined use of FESEM imaging with biochemical and genetic
      manipulation, in cell-free systems and in mammalian cells.

PMID- 22405001
TI  - The UBAP1 subunit of ESCRT-I interacts with ubiquitin via a SOUBA domain.
AB  - The endosomal sorting complexes required for transport (ESCRTs) facilitate
      endosomal sorting of ubiquitinated cargo, MVB biogenesis, late stages of
      cytokinesis, and retroviral budding. Here we show that ubiquitin associated
      protein 1 (UBAP1), a subunit of human ESCRT-I, coassembles in a stable 1:1:1:1
      complex with Vps23/TSG101, VPS28, and VPS37. The X-ray crystal structure of the C
      terminal region of UBAP1 reveals a domain that we describe as a solenoid of
      overlapping UBAs (SOUBA). NMR analysis shows that each of the three rigidly
      arranged overlapping UBAs making up the SOUBA interact with ubiquitin. We
      demonstrate that UBAP1-containing ESCRT-I is essential for degradation of
      antiviral cell-surface proteins, such as tetherin (BST-2/CD317), by viral
      countermeasures, namely, the HIV-1 accessory protein Vpu and the Kaposi sarcoma
      associated herpesvirus (KSHV) ubiquitin ligase K5.

PMID- 22405002
TI  - Moonlighting by different stressors: crystal structure of the chaperone species
      of a 2-Cys peroxiredoxin.
AB  - 2-Cys peroxiredoxins (Prxs) play two different roles depending on the
      physiological status of the cell. They are thioredoxin-dependent peroxidases
      under low oxidative stress and ATP-independent chaperones upon exposure to high
      peroxide concentrations. These alternative functions have been associated with
      changes in the oligomerization state from low-(LMW) to high-molecular-weight
      (HMW) species. Here we present the structures of Schistosoma mansoni PrxI in both
      states: the LMW decamer and the HMW 20-mer formed by two stacked decamers. The
      latter is the structure of a 2-Cys Prx chaperonic form. Comparison of the
      structures sheds light on the mechanism by which chemical stressors, such as high
      H(2)O(2) concentration and acidic pH, are sensed and translated into a functional
      switch in this protein family. We also propose a model to account for the in vivo
      formation of long filaments of stacked Prx rings.

PMID- 22405003
TI  - Mechanistic insights into the activation of Rad51-mediated strand exchange from
      the structure of a recombination activator, the Swi5-Sfr1 complex.
AB  - Rad51 forms a helical filament on single-stranded DNA and promotes strand
      exchange between two homologous DNA molecules during homologous recombination.
      The Swi5-Sfr1 complex interacts directly with Rad51 and stimulates strand
      exchange. Here we describe structural and functional aspects of the complex. Swi5
      and the C-terminal core domain of Sfr1 form an essential activator complex with a
      parallel coiled-coil heterodimer joined firmly together via two previously
      uncharacterized leucine-zipper motifs and a bundle. The resultant coiled coil is
      sharply kinked, generating an elongated crescent-shaped structure suitable for
      transient binding within the helical groove of the Rad51 filament. The N-terminal
      region of Sfr1, meanwhile, has an interface for binding of Rad51. Our data
      suggest that the snug fit resulting from the complementary geometry of the
      heterodimer activates the Rad51 filament and that the N-terminal domain of Sfr1
      plays a role in the efficient recruitment of the Swi5-Sfr1 complex to the Rad51
      filaments.

PMID- 22405004
TI  - Constructing and validating initial Calpha models from subnanometer resolution
      density maps with pathwalking.
AB  - A significant number of macromolecular structures solved by electron cryo
      microscopy and X-ray crystallography obtain resolutions of 3.5-6A, at which
      direct atomistic interpretation is difficult. To address this, we developed
      pathwalking, a semi-automated protocol to enumerate reasonable Calpha models from
      near-atomic resolution density maps without a structural template or sequence
      structure correspondence. Pathwalking uses an approach derived from the Traveling
      Salesman Problem to rapidly generate an ensemble of initial models for individual
      proteins, which can later be optimized to produce full atomic models. Pathwalking
      can also be used to validate and identify potential structural ambiguities in
      models generated from near-atomic resolution density maps. In this work, examples
      from the EMDB and PDB are used to assess the broad applicability and accuracy of
      our method. With the growing number of near-atomic resolution density maps from
      cryo-EM and X-ray crystallography, pathwalking can become an important tool in
      modeling protein structures.

PMID- 22405005
TI  - EM-fold: de novo atomic-detail protein structure determination from medium
      resolution density maps.
AB  - Electron density maps of membrane proteins or large macromolecular complexes are
      frequently only determined at medium resolution between 4 A and 10 A, either by
      cryo-electron microscopy or X-ray crystallography. In these density maps, the
      general arrangement of secondary structure elements (SSEs) is revealed, whereas
      their directionality and connectivity remain elusive. We demonstrate that the
      topology of proteins with up to 250 amino acids can be determined from such
      density maps when combined with a computational protein folding protocol.
      Furthermore, we accurately reconstruct atomic detail in loop regions and amino
      acid side chains not visible in the experimental data. The EM-Fold algorithm
      assembles the SSEs de novo before atomic detail is added using Rosetta. In a
      benchmark of 27 proteins, the protocol consistently and reproducibly achieves
      models with root mean square deviation values <3 A.

PMID- 22405007
TI  - Structure of the human obesity receptor leptin-binding domain reveals the
      mechanism of leptin antagonism by a monoclonal antibody.
AB  - Leptin regulates energy homeostasis, fertility, and the immune system, making it
      an important drug target. However, due to a complete lack of structural data for
      the obesity receptor (ObR), leptin's mechanism of receptor activation remains
      poorly understood. We have crystallized the Fab fragment of a leptin-blocking
      monoclonal antibody (9F8), both in its uncomplexed state and bound to the leptin
      binding domain (LBD) of human ObR. We describe the structure of the LBD-9F8 Fab
      complex and the conformational changes in 9F8 associated with LBD binding. A
      molecular model of the putative leptin-LBD complex reveals that 9F8 Fab blocks
      leptin binding through only a small (10%) overlap in their binding sites, and
      that leptin binding is likely to involve an induced fit mechanism. This crystal
      structure of the leptin-binding domain of the obesity receptor will facilitate
      the design of therapeutics to modulate leptin signaling.

PMID- 22405006
TI  - Variable lymphocyte receptor recognition of the immunodominant glycoprotein of
      Bacillus anthracis spores.
AB  - Variable lymphocyte receptors (VLRs) are the adaptive immune receptors of jawless
      fish, which evolved adaptive immunity independent of other vertebrates. In lieu
      of the immunoglobulin fold-based T and B cell receptors, lymphocyte-like cells of
      jawless fish express VLRs (VLRA, VLRB, or VLRC) composed of leucine-rich repeats
      and are similar to toll-like receptors (TLRs) in structure, but antibodies (VLRB)
      and T cell receptors (VLRA and VLRC) in function. Here, we present the structural
      and biochemical characterization of VLR4, a VLRB, in complex with BclA, the
      immunodominant glycoprotein of Bacillus anthracis spores. Using a combination of
      crystallography, mutagenesis, and binding studies, we delineate the mode of
      antigen recognition and binding between VLR4 and BclA, examine commonalities in
      VLRB recognition of antigens, and demonstrate the potential of VLR4 as a
      diagnostic tool for the identification of B. anthracis spores.

PMID- 22405008
TI  - Capsomer dynamics and stabilization in the T = 12 marine bacteriophage SIO-2 and
      its procapsid studied by CryoEM.
AB  - We report the subnanometer cryo-electron microscopy (cryoEM) reconstruction of a
      marine siphovirus, the Vibrio phage SIO-2. This phage is lytic for related Vibrio
      species with significant ecological importance, including the broadly
      antagonistic bacterium Vibrio sp. SWAT3. The three-dimensional structure of the
      800 A SIO-2, icosahedrally averaged head of the tailed particle revealed a T = 12
      quasi-symmetry not previously described in a bacteriophage. Two morphologically
      distinct types of auxiliary proteins were also identified; one species bound to
      the surface of hexamers, and the other bound to pentamers. The secondary
      structure, evident in the electron density, shows that the major capsid protein
      has the HK97-like fold. The three-dimensional structure of the procapsid form,
      also presented here, has no "decoration" proteins and reveals a capsomer
      organization due to the constraints of the T = 12 symmetry.

PMID- 22405010
TI  - The structure of the 26S proteasome subunit Rpn2 reveals its PC repeat domain as
      a closed toroid of two concentric alpha-helical rings.
AB  - The 26S proteasome proteolyses ubiquitylated proteins and is assembled from a 20S
      proteolytic core and two 19S regulatory particles (19S-RP). The 19S-RP
      scaffolding subunits Rpn1 and Rpn2 function to engage ubiquitin receptors. Rpn1
      and Rpn2 are characterized by eleven tandem copies of a 35-40 amino acid repeat
      motif termed the proteasome/cyclosome (PC) repeat. Here, we reveal that the
      eleven PC repeats of Rpn2 form a closed toroidal structure incorporating two
      concentric rings of alpha helices encircling two axial alpha helices. A rod-like
      N-terminal domain consisting of 17 stacked alpha helices and a globular C
      terminal domain emerge from one face of the toroid. Rpn13, an ubiquitin receptor,
      binds to the C-terminal 20 residues of Rpn2. Rpn1 adopts a similar conformation
      to Rpn2 but differs in the orientation of its rod-like N-terminal domain. These
      findings have implications for understanding how 19S-RPs recognize, unfold, and
      deliver ubiquitylated substrates to the 20S core.

PMID- 22405009
TI  - Structural dynamics associated with intermediate formation in an archetypal
      conformational disease.
AB  - In conformational diseases, native protein conformers convert to pathological
      intermediates that polymerize. Structural characterization of these key
      intermediates is challenging. They are unstable and minimally populated in
      dynamic equilibria that may be perturbed by many analytical techniques. We have
      characterized a forme fruste deficiency variant of alpha(1)-antitrypsin
      (Lys154Asn) that forms polymers recapitulating the conformer-specific neo-epitope
      observed in polymers that form in vivo. Lys154Asn alpha(1)-antitrypsin populates
      an intermediate ensemble along the polymerization pathway at physiological
      temperatures. Nuclear magnetic resonance spectroscopy was used to report the
      structural and dynamic changes associated with this. Our data highlight an
      interaction network likely to regulate conformational change and do not support
      the recent contention that the disease-relevant intermediate is substantially
      unfolded. Conformational disease intermediates may best be defined using powerful
      but minimally perturbing techniques, mild disease mutants, and physiological
      conditions.

PMID- 22405011
TI  - Recognition pliability is coupled to structural heterogeneity: a calmodulin
      intrinsically disordered binding region complex.
AB  - Protein interactions within regulatory networks should adapt in a spatiotemporal
      dependent dynamic environment, in order to process and respond to diverse and
      versatile cellular signals. However, the principles governing recognition
      pliability in protein complexes are not well understood. We have investigated a
      region of the intrinsically disordered protein myelin basic protein (MBP(145
      165)) that interacts with calmodulin, but that also promiscuously binds other
      biomolecules (membranes, modifying enzymes). To characterize this interaction, we
      implemented an NMR spectroscopic approach that calculates, for each conformation
      of the complex, the maximum occurrence based on recorded pseudocontact shifts and
      residual dipolar couplings. We found that the MBP(145-165)-calmodulin interaction
      is characterized by structural heterogeneity. Quantitative comparative analysis
      indicated that distinct conformational landscapes of structural heterogeneity are
      sampled for different calmodulin-target complexes. Such structural heterogeneity
      in protein complexes could potentially explain the way that transient and
      promiscuous protein interactions are optimized and tuned in complex regulatory
      networks.

PMID- 22405012
TI  - Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo
      electron microscopy.
AB  - The eukaryotic origin recognition complex (ORC) interacts with and remodels
      origins of DNA replication prior to initiation in S phase. Here, we report a
      single-particle cryo-EM-derived structure of the supramolecular assembly
      comprising Saccharomyces cerevisiae ORC, the replication initiation factor Cdc6,
      and double-stranded ARS1 origin DNA in the presence of ATPgammaS. The six
      subunits of ORC are arranged as Orc1:Orc4:Orc5:Orc2:Orc3, with Orc6 binding to
      Orc2. Cdc6 binding changes the conformation of ORC, in particular reorienting the
      Orc1 N-terminal BAH domain. Segmentation of the 3D map of ORC-Cdc6 on DNA and
      docking with the crystal structure of the homologous archaeal Orc1/Cdc6 protein
      suggest an origin DNA binding model in which the DNA tracks along the interior
      surface of the crescent-like ORC. Thus, ORC bends and wraps the DNA. This model
      is consistent with the observation that binding of a single Cdc6 extends the ORC
      footprint on origin DNA from both ends.

PMID- 22405014
TI  - Architecture of a dodecameric bacterial replicative helicase.
AB  - Hexameric DnaB helicases are often loaded at DNA replication forks by interacting
      with the initiator protein DnaA and/or a helicase loader (DnaC in Escherichia
      coli). These loaders are not universally required, and DnaB from Helicobacter
      pylori was found to bypass DnaC when expressed in E. coli cells. The crystal
      structure of Helicobacter pylori DnaB C-terminal domain (HpDnaB-CTD) reveals a
      large two-helix insertion (named HPI) in the ATPase domain that protrudes away
      from the RecA fold. Biophysical characterization and electron microscopy (EM)
      analysis of the full-length protein show that HpDnaB forms head-to-head double
      hexamers remarkably similar to helicases found in some eukaryotes, archaea, and
      viruses. The docking of the HpDnaB-CTD structure into EM reconstruction of HpDnaB
      provides a model that shows how hexamerization of the CTD is facilitated by HPI
      HPI interactions. The HpDnaB double-hexamer architecture supports an alternative
      strategy to load bacterial helicases onto forks in the absence of helicase
      loaders.

PMID- 22405013
TI  - Structure of the Cmr2 subunit of the CRISPR-Cas RNA silencing complex.
AB  - Cmr2 is the largest and an essential subunit of a CRISPR RNA-Cas protein complex
      (the Cmr complex) that cleaves foreign RNA to protect prokaryotes from invading
      genetic elements. Cmr2 is thought to be the catalytic subunit of the effector
      complex because of its N-terminal HD nuclease domain. Here, however, we report
      that the HD domain of Cmr2 is not required for cleavage by the complex in vitro.
      The 2.3A crystal structure of Pyrococcus furiosus Cmr2 (lacking the HD domain)
      reveals two adenylyl cyclase-like and two alpha-helical domains. The adenylyl
      cyclase-like domains are arranged as in homodimeric adenylyl cyclases and bind
      ADP and divalent metals. However, mutagenesis studies show that the metal- and
      ADP-coordinating residues of Cmr2 are also not critical for cleavage by the
      complex. Our findings suggest that another component provides the catalytic
      function and that the essential role by Cmr2 does not require the identified ADP-
      or metal-binding or HD domains in vitro.

PMID- 22405015
TI  - Marking and curving.

PMID- 22405016
TI  - Buddhist thought and nursing: a hermeneutic exploration.
AB  - In this paper I lay out the ground for a creative dialogue between Buddhist
      thought and contemporary nursing. I start from the observation that in tracing an
      arc from the existential human experience of suffering to finding compassionate
      responses to suffering in everyday practice Buddhist thought already appears to
      present significant affinities with nursing as a practice discipline. I discuss
      some of the complexities of entering into a cross-cultural dialogue, which is
      already well under way in the working out of Western forms of Buddhism, and which
      is beginning to be reflected in nursing literature. I introduce philosophical
      hermeneutics as a useful framework for elaborating an open and constructive
      exchange. I then discuss key Mahayana Buddhist concepts of emptiness and two
      truths that lead to a dynamic and open way of understanding reality and
      responding in the world. I turn to examples of original texts to give a flavour
      of the varied and distinctive forms of literature in the Buddhist tradition. This
      is intended partly to keep the reader alert to cultural difference (from a
      Western standpoint, that is) while exploring the creative potential of Buddhist
      thought. Hermeneutics again provides a framework for interpretation. This paper
      establishes a philosophical ground for a critical and creative dialogue between
      Buddhist thought and nursing.

PMID- 22405017
TI  - Nursing intuition: a valid form of knowledge.
AB  - An understanding of the nature and development of nursing intuition can help
      nurse educators foster it in young nurses and give clinicians more confidence in
      this aspect of their knowledge, allowing them to respond with greater assurance
      to their intuitions. In this paper, accounts from philosophy and neurophysiology
      are used to argue that intuition, specifically nursing intuition, is a valid form
      of knowledge. The paper argues that nursing intuition, a kind of practical
      intuition, is composed of four distinct aspects that include: (1) embodied
      knowledge rather like that knowledge we have when we have learned to ride a
      bicycle; (2) well-trained sensory perceptions attentive to subtle details of
      complex, often rapidly changing situations; (3) a significant store of pertinent
      conceptual knowledge; and (4) a history of habitual actions intentionally
      directed towards achieving the best outcomes for our patients. Contemporary
      neurophysiology research strongly suggests that human persons experience other
      persons such that they directly understand the meaning of a variety of different
      human actions, intentions, emotions, and sensations in immediate, non-reflective,
      and non-conceptual perceptions. This research is supported by the philosophical
      theories of Jacques Maritain and Yves R. Simon found in their accounts of
      practical knowledge. Together, these accounts offer us a rich view of the reality
      of nursing intuition that helps us understand why we find intuitive actions in
      some but not all nurses and gives us some specific information about how to
      develop intuition in young nurses. Finally, this research shows us a path for
      further research.

PMID- 22405018
TI  - Questioning the use value of qualitative research findings.
AB  - In this paper the use value of qualitative research findings to nurses in
      practice is questioned. More precisely it is argued that, insofar as action
      follows belief then, in all but the rarest of cases, the beliefs that nurses in
      practice can justifiably derive from or form on the basis of qualitative research
      findings do not sanction action in the world and the assumption, apparently
      widely held, that qualitative research can as evidence productively inform
      practice collapses. If qualitative research does not have a substantive action
      guiding potential then, in consequence, three conclusions are permitted. First,
      regarding the requirement that nurses ground actions on evidence, regulators
      should redraft methodologically neutral or permissive guidelines to specify the
      sorts of research evidence that can serve this function. Second, qualitative
      methodologies should receive less prominence in nurse education programmes.
      Third, qualitative researchers should make it clear that their work cannot inform
      practice. Alternatively, if this claim is advanced the process by which this is
      to be achieved should be explicitly stated.

PMID- 22405019
TI  - Concurrent analysis: a pragmatic justification.
AB  - Concurrent analysis (CA) is a process of synthesizing conceptually equivalent
      data for the purpose of producing a coherent and predictive model in social
      science. The process of CA is detailed. In short, CA uses Thagard's concept of
      coherence as a method of explicating links between mental representations. The
      product is a wide analysis of all pertinent data. This paper provides a
      philosophical justification for the need and function of CA. The paper is divided
      into three sections. The first section reviews some problems with the
      metasynthetic literature. The purpose of this is that CA can be initially
      understood as a branch of this type of synthesis. The second section links
      Risjord's post-paradigmatic position to Rorty's version of pragmatism in order to
      show the importance of the concept of coherence to these views. The reason for
      linking these issues is that CA is grounded in rejection of ontological priority.
      Instead it prioritises a pragmatic conception of coherence. The final section
      details the mechanics of CA. Concurrent analysis is presented as the most
      coherent method of synthesizing certain types of narrative evidence if pragmatism
      is prioritized over ontology. Examples are given from published studies using CA
      to illustrate the detail of the analysis and the practical value of the product.
      The examples show that CA appears useful under certain circumstances. These
      circumstances will be specified, and strengths and weaknesses of the method will
      be discussed.

PMID- 22405020
TI  - A reply to 'Scepticism about the virtue ethics approach to nursing ethics' by
      Stephen Holland: the relevance of virtue in nursing ethics.

PMID- 22405021
TI  - Letter to the editor. Jamesian pragmatism.

PMID- 22405023
TI  - A 3-year follow-up study on the risk of stroke among patients with conjunctival
      haemorrhage.
AB  - PURPOSE: To the best of our knowledge, no large population-based studies on the
      relationship between conjunctival haemorrhage and stroke have been conducted to
      date. Using a nationwide population-based data set, this study investigated the
      relationship between conjunctival haemorrhage and the subsequent risk of stroke
      within a 3-year period following diagnosis. METHODS: We analysed data sourced
      from the Taiwan Longitudinal Health Insurance Database 2000. The study cohort
      consisted of 17 349 patients with conjunctival haemorrhage and 86 745 comparison
      subjects. Each patient was individually tracked for a 3-year period from their
      index date to identify all those who had subsequently received a diagnosis of
      stroke. RESULTS:   The incidence rate of stroke was 2.44 (95% CI = 2.31-2.55) per
      100 person-years in patients with conjunctival haemorrhage and 1.63 (95% CI =
      1.59-1.68) per 100 person-years in comparison patients. After adjusting for
      patients' monthly income and geographic location, as well as for hypertension,
      atrial fibrillation, diabetes, hyperlipidaemia and coronary heart disease,
      stratified Cox proportional hazards regressions revealed a statistically
      significant hazard ratio for stroke in patients with conjunctival haemorrhage (HR
      = 1.33; 95% CI = 1.24-1.42, p < 0.001). CONCLUSIONS: In this study, patients with
      conjunctival haemorrhage were found to be at a significant risk of stroke during
      a 3-year follow-up period after diagnosis.

PMID- 22405024
TI  - The successful introduction of an adapted form of the mini extra corporeal
      circulation used for cardiac surgery in an obese patient.
AB  - Obese patients undergoing cardiac surgery have been shown to have a high risk of
      developing postoperative complications, specifically: increased length of
      hospital stay, readmission to intensive care unit, acute renal failure, deep
      sternal wound infections and new onset of atrial fibrillation.A custom-made
      circuit was created to allow the use of Mini Extra Corporeal Circulation (MECC)
      but permitting the switch to a closed siphon drainage system in the case of
      difficulties.To limit artificial surface contact a small oxygenating device
      (Admiral, Eurosets) was employed in spite of the patients size. This adapted
      circuit permits a feasible and safer approach to using MECC. This report suggests
      that smaller oxygenators could be integrated into clinical practice in an adult
      MECC configuration, even for more obese patients, limiting artificial surface
      contact.

PMID- 22405025
TI  - Association between hippocampal volume and serum adiponectin in patients with
      type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus (DM) is associated with cognitive dysfunction and
      hippocampus volume. The aim of the present study was to test the hypothesis that
      the level of the adipocytokine adiponectin correlates with hippocampus volume and
      insulin resistance in patients with type 2 DM. A total of 45 patients with type 2
      DM were divided into two groups: a low adiponectin group and a normal adiponectin
      group. Hippocampus volume was measured by computer-assisted analysis using a
      magnetic resonance imaging (MRI) voxel-based specific regional analysis system
      developed for the study of Alzheimer's disease as the end point for assessment of
      hippocampus volume. Mean hippocampus volume was lower in the low adiponectin
      group than in the normal adiponectin group (P<.0001). Fasting serum
      concentrations of glucose (P<.05) and insulin (P<.0001), and homeostasis model
      assessment index (P<.0001), were all higher in the low adiponectin group than in
      the normal adiponectin group. Multiple regression analysis showed that
      hippocampus volume independently predicted serum adiponectin level. These results
      suggest that circulating levels of adiponectin are related to hippocampus volume
      in patients with type 2 DM.

PMID- 22405026
TI  - Complications and risk factors in 2731 diagnostic mini-laparoscopies in patients
      with liver disease.
AB  - BACKGROUND/AIMS: Mini-laparoscopy (ML) allows macroscopic assessment and biopsy
      under direct vision and therefore is a valuable technique in the diagnosis of
      liver disease. Herein we report procedure-related complications and risk factors.
      METHODS: A total of 2731 consecutive patients underwent diagnostic ML at two
      university hospitals (June 1996-December 2007). ML was performed using standard
      technique with a 1.9mm optical instrument. Coagulation of the liver biopsy site
      was performed with APC. The following variables were analysed as risk factors for
      complications: platelet count (<50/nL), international normalized ratio (INR)
      (>1.5), Cirrhosis, signs of portal hypertension, prior abdominal surgery.
      RESULTS: Major complications occurred in 1.0% (n=27) of patients and these were,
      delayed bleeding from the liver biopsy site or abdominal wall (in 0.7% of
      patients) and intestinal perforation (in 0.3% of patients). Two patients died
      after severe haemorrhage (mortality 0.07%); the other patients recovered without
      sequelae. Bleeding risk was increased in patients with low platelets (OR=6.1),
      increased INR (OR=8.9), cirrhosis (OR=1.9) and portal hypertension (OR=2.1).
      Logistic regression showed a significant correlation only for the concurrence of
      low platelets and increased INR (P = 0.001; OR=14.1); bootstrap analysis
      identified INR >1.5 as significant predictor (P = 0.0002). Prior abdominal
      surgery did not carry a significant risk for intestinal perforation (OR=1.1; P =
      0.142), unless abdominal adhesions were present (OR=9.5; P = 0.0002). None of the
      patients required surgery for intestinal perforation. CONCLUSION: Mini
      laparoscopy is a diagnostic technique with a low complication rate. However, in
      patients with increased INR, low platelets or after extensive abdominal surgery,
      complications may occur in up to 5%.

PMID- 22405027
TI  - Design and baseline characteristics of the 10 Small Steps Study: a randomised
      controlled trial of an intervention to promote healthy behaviour using a
      lifestyle score and personalised feedback.
AB  - BACKGROUND: Non-communicable diseases (NCDs) are the leading causes of death
      globally and are associated with a limited set of common, modifiable health
      behaviours: tobacco use, physical inactivity, harmful use of alcohol and
      unhealthy diet. General practice offers an ideal avenue for addressing such
      health behaviours on a population-wide basis. This paper describes the protocol
      of a multiple health behaviour change intervention designed for implementation in
      general practice and summarises the baseline characteristics of its participants.
      METHOD/DESIGN: The 10 Small Steps (10SS) study, a randomised controlled trial,
      involved 4,678 adult general practice patients in Queensland, Australia. Self
      reported data were collected to establish the proportion of participants meeting
      recommended guidelines for ten health behaviours: physical activity, body mass
      index, alcohol, smoking and six dietary behaviours. Participants were randomised
      to four groups: contact at baseline only ('single intervention' and corresponding
      control group) and contact at baseline and 3 months ('dual intervention' and
      corresponding control group). At each contact the participants received a
      computer-tailored feedback and one page information sheet according to their
      allocation to intervention or control groups. Change in the intervention group
      compared to the control group was assessed at 3 and12 months after baseline data
      collection.Responses were summed to calculate an individual lifestyle score (the
      Prudence Score), which ranged from 0 to 10. The baseline response was 56.5% (4678
      of 8343 invited participants) and the study sample was primarily female (68.7%)
      with an average age of 47 years. The mean Prudence Score was 5.8 (95%CI 5.75
      5.85). DISCUSSION: Baseline data from the 10SS study show that nearly all
      participants engage in some health behaviours but relatively few adhere
      simultaneously to a core set of dietary and lifestyle behaviours associated with
      risk of NCDs. Ample scope exists to improve health behaviour to reduce NCDs in
      the general practice setting and the 10SS study trial will provide data on the
      extent to which a minimal computer-tailored intervention can meet this objective.
      The protocol developed for the 10SS study has potential for translation into
      routine general practice as it has minimal impact on practice routine whilst
      contributing to primary prevention objectives. TRIAL REGISTRATION: The Australian
      New Zealand Clinical Trials Registry ACTRN12611001213932.

PMID- 22405028
TI  - Role of interleukin-12 and - 18 in lupus-like syndrome patients with statin use:
      comment on: Association between statin use and lupus-like syndrome using
      spontaneous reports.

PMID- 22405029
TI  - The role of complement in the antiphospholipid syndrome: a novel mechanism for
      pregnancy morbidity.
AB  - OBJECTIVES: Despite the experimental research data on antiphospholipid syndrome
      (APS), the pathogenesis of thrombosis and fetal loss remains unknown. The
      objective of this study was to analyze the major advances in the field of
      complement activation as a possible thrombosis mechanism in the APS. METHODS: The
      authors conducted a systemic analysis of the English literature and summarized
      both animal and human data that indicate the inappropriate complement activation
      as a mechanism causing thrombosis in the APS. RESULTS: The important role of
      complement activation in the pathogenesis of fetal loss was established using
      mice deficient in a complement regulatory protein. Further studies have shown
      that the infusion of human IgG antiphospholipid antibodies (aPL) induced fetal
      loss in pregnant mice, an effect that was abrogated by the concurrent
      administration of a C3 convertase inhibitor. Further studies suggested that C5a
      and neutrophils were the key components responsible for fetal injury. Moreover,
      use of F(ab)'2 fragments of aPL suggested the complement activation occurred
      mainly via the classical pathway. Other studies using models of induced
      thrombosis suggested that antibodies against beta2GPI required the presence of
      terminal complement components to induce thrombus formation, and mice deficient
      in C3 or C5 were found to be resistant to aPL-induced thrombosis. Based on the
      aforementioned findings, it has been suggested that heparin prevents fetal loss
      in patients with APS by inhibiting complement activation rather than by its
      anticoagulant effect. CONCLUSIONS: The studies on complement are significant
      because they shift the focus of research in APS from thrombosis to inflammation.
      However, as human data are limited, more clinical research is necessary before
      the above findings translate in changes in the management of APS.

PMID- 22405030
TI  - Potential selective inhibitors against Rv0183 of Mycobacterium tuberculosis
      targeting host lipid metabolism.
AB  - Tuberculosis is the second leading infectious killer with 9 million new cases in
      2009. Extensive use of pathogen's lipid metabolism especially in utilizing the
      host lipids and virulence highlights the importance of exported lipid
      catabolizing enzymes. Current study aims to emphasize the importance of Rv0183,
      an exported monoacylglycerol lipase, involved in metabolizing the host cell
      membrane lipids. Sequence analysis and homology modeling shows Rv0183 is highly
      conserved throughout mycobacterial species even in Mycobacterium leprae and also
      significantly divergent from mammalian lipases. Additionally, employing virtual
      screening using NCI diversity set and ZINC database with criteria of molecules
      with higher predicted free energy of binding toward Rv0183 than human lipase,
      potential inhibitors have been identified for Rv0183. A tautomer of ZINC13451138,
      known inhibitor for HIV-1 integrase is the best hit with difference in free
      energy of binding of 8.72 kcal/mol. The sequence and structure analysis were
      helpful in identifying the ligand binding sites and molecular function of the
      mycobacterial specific monoacylglycerol lipase. Rv0183 represents a suitable and
      promising drug target and is also a step towards understanding dormancy
      development and reactivation, thereby addressing pathogen's drug resistance.
      Experimental studies on the discovered potential inhibitors in this virtual
      screen should further validate the therapeutic utility of Rv0183.

PMID- 22405031
TI  - A systematic critical review on MRI in spondyloarthritis.
AB  - INTRODUCTION: Magnetic resonance imaging (MRI) has been proven capable of showing
      inflammatory and structural changes in patients with spondyloarthritis (SpA) and
      has become widely used in the diagnosis of SpA. Despite this, no systematic
      reviews evaluate the diagnostic utility of MRI for SpA. Therefore, the objective
      of this systematic review was to determine the evidence for the utility of MRI in
      the clinical diagnosis of SpA. The aims were to identify which MRI findings are
      associated with the diagnosis of SpA and to quantify this association. METHODS:
      MEDLINE and EMBASE were electronically searched. Inclusion criteria were cross
      sectional or longitudinal case-control or cohort MRI studies. The studies
      required a group with either SpA or inflammatory back pain (IBP) and a non-case
      group without SpA or IBP. Each group required a minimum of 20 participants. The
      included articles had to report results containing raw numbers suitable for the
      construction of two-by-two tables or report results by sensitivity and
      specificity for cross-sectional studies or odds ratios, relative risk ratios, or
      likelihood ratios for longitudinal studies. Method quality was assessed by using
      criteria based on the QUADAS tool. RESULTS: In total, 2,395 articles were
      identified in MEDLINE and EMBASE before November 2011. All articles were reviewed
      by title and abstract. Seventy-seven articles were reviewed by full text, and 10
      met the inclusion criteria. Two were considered of high quality: one evaluated
      the sacroiliac joints, and the other, the spine. Because of the small number of
      high-quality studies, a meta-analysis was not performed. The two high-quality
      studies found a positive association between MRI findings (bone marrow edema,
      erosions, fat infiltrations, global assessment of sacroiliitis, and ankylosis)
      and the diagnosis of IBP and SpA. CONCLUSION: In this review, several MRI
      findings were found to be associated with SpA. However, because of the small
      number of high-quality studies, the evidence for the utility of MRI in the
      diagnosis of SpA must be considered limited. Therefore, caution should be taken
      to ensure that inflammatory and structural MRI findings are not interpreted as
      being more specific for SpA than is supported by research.

PMID- 22405032
TI  - Transgenic expression of lactoferrin imparts enhanced resistance to head blight
      of wheat caused by Fusarium graminearum.
AB  - BACKGROUND: The development of plant gene transfer systems has allowed for the
      introgression of alien genes into plant genomes for novel disease control
      strategies, thus providing a mechanism for broadening the genetic resources
      available to plant breeders. Using the tools of plant genetic engineering, a
      broad-spectrum antimicrobial gene was tested for resistance against head blight
      caused by Fusarium graminearum Schwabe, a devastating disease of wheat (Triticum
      aestivum L.) and barley (Hordeum vulgare L.) that reduces both grain yield and
      quality. RESULTS: A construct containing a bovine lactoferrin cDNA was used to
      transform wheat using an Agrobacterium-mediated DNA transfer system to express
      this antimicrobial protein in transgenic wheat. Transformants were analyzed by
      Northern and Western blots to determine lactoferrin gene expression levels and
      were inoculated with the head blight disease fungus F. graminearum. Transgenic
      wheat showed a significant reduction of disease incidence caused by F.
      graminearum compared to control wheat plants. The level of resistance in the
      highly susceptible wheat cultivar Bobwhite was significantly higher in transgenic
      plants compared to control Bobwhite and two untransformed commercial wheat
      cultivars, susceptible Wheaton and tolerant ND 2710. Quantification of the
      expressed lactoferrin protein by ELISA in transgenic wheat indicated a positive
      correlation between the lactoferrin gene expression levels and the levels of
      disease resistance. CONCLUSIONS: Introgression of the lactoferrin gene into elite
      commercial wheat, barley and other susceptible cereals may enhance resistance to
      F. graminearum.

PMID- 22405033
TI  - Attitudes toward life-sustaining treatment: the role of race/ethnicity.
AB  - This study explores attitudes regarding life-sustaining treatments between Korean
      American and Mexican American older adults. A cross sectional design was employed
      to survey 122 older adults residing in an urban area on the West Coast (64 Korean
      Americans and 58 Mexican Americans). Face to face interviews were conducted using
      a structured questionnaire. Results show that Mexican Americans as compared to
      Korean American older adults hold more favorable attitudes toward life-sustaining
      treatments. Participants who were male were more likely to have positive
      attitudes toward life-sustaining treatments than female. Findings emphasize the
      importance of culturally sensitive end-of-life care practices which consider
      cultural variations in life-sustaining treatment preferences.

PMID- 22405034
TI  - The visualisation and speed of kill of wound isolates on a silver alginate
      dressing.
AB  - In chronic wound management, alginate dressings are used to absorb exudate and
      reduce the microbial burden. Silver alginate offers the added benefit of an
      additional antimicrobial pressure on contaminating microorganisms. This present
      study compares the antimicrobial activity of a RESTORE silver alginate dressing
      with a silver-free control dressing using a combination of in vitro culture and
      imaging techniques. The wound pathogens examined included Candida albicans,
      Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, beta-haemolytic
      Streptococcus, and strictly anaerobic bacteria. The antimicrobial efficacy of the
      dressings was assessed using log(10)  reduction and 13-day corrected zone of
      inhibition (CZOI) time-course assays. Confocal laser scanning microscopy (CLSM)
      was used to visualise the relative proportions of live/dead microorganisms
      sequestered into the dressings over 24 hours and estimate the comparative speed
      of kill. The RESTORE silver alginate dressing showed significantly greater
      log(10)  reductions and CZOIs for all microorganisms compared with the control,
      indicating the antimicrobial effect of ionic silver. Antimicrobial activity was
      evident against all test organisms for up to 5 days and, in some cases, up to 12
      days following an on-going microbial challenge. Imaging bacteria sequestered in
      the silver-free dressing showed that each microbial species aggregated in the
      dressing and remained viable for more than 20 hours. Growth was not observed
      inside of the dressing, indicating a possible microbiostatic effect of the
      alginate fibres. In comparison, organisms in the RESTORE silver alginate dressing
      were seen to lose viability at a considerably greater rate. After 16 hours of
      contact with the RESTORE silver alginate dressing, >90% of cells of all bacteria
      and yeast were no longer viable. In conclusion, collectively, the data highlights
      the rapid speed of kill and antimicrobial suitability of this RESTORE silver
      alginate dressing on wound isolates and highlights its overwhelming ability to
      manage a microbial wound bioburden in the management of infected wounds.

PMID- 22405035
TI  - Applications of multi-walled carbon nanotube in electronic packaging.
AB  - Thermal management of integrated circuit chip is an increasing important
      challenge faced today. Heat dissipation of the chip is generally achieved through
      the die attach material and solders. With the temperature gradients in these
      materials, high thermo-mechanical stress will be developed in them, and thus they
      must also be mechanically strong so as to provide a good mechanical support to
      the chip. The use of multi-walled carbon nanotube to enhance the thermal
      conductivity, and the mechanical strength of die attach epoxy and Pb-free solder
      is demonstrated in this work.

PMID- 22405036
TI  - Exendin-4 increases the expression of hypoxia-inducible factor-1alpha in rat
      islets and preserves the endocrine cell volume of both free and macroencapsulated
      islet grafts.
AB  - In this study, we evaluated the effects of exendin-4 on free and encapsulated
      islet grafts in a rodent model. We also investigated the role of a transcription
      factor, hypoxia-inducible factor-1 (HIF-1), in mediating the beneficial effects
      of exendin-4. Diabetic athymic mice were transplanted  with free rat islets under
      the kidney capsule or with macroencapsulated rat islets SC with or without
      exendin-4, islet preculture (exendin-4 0.1 nM for 20 h), and/or recipient
      treatment (IP 100 ng/day, day 0-7). The mice were followed for 4 weeks and the
      graft function and beta-cell  volume were evaluated. The effects of exendin-4 on
      islet HIF-1alpha mRNA and protein expression and on ATP content in a rat
      insulinoma cell line (INS-1E) were also examined. Preculture with exendin-4
      followed by recipient treatment improved the outcome of both free (73% graft
      function vs.  26% in controls, p = 0.03) and macroencapsulated islet grafts (100%
      vs. 25% in controls, p = 0.02). In macroencapsulated grafts, the exendin-4
      treated group had significantly larger endocrine volume, less graft necrosis, and
      more blood vessels around the capsule. In rat islets  cultured with exendin-4,
      HIF-1alpha mRNA and protein expression were significantly enhanced. ATP content
      was increased in exendin-4-treated INS-1E cells under hypoxic conditions. The
      improved functional outcome after transplantation of a marginal islet mass with a
      brief initial treatment  with exendin-4 is related to a larger surviving
      endocrine cell volume. Exendin-4 may improve islet graft resistance to hypoxia
      during the peritransplant period by increasing the expression of HIF-1alpha.

PMID- 22405037
TI  - Liver transplantation followed by allogeneic hematopoietic stem cell
      transplantation for atypical mevalonic aciduria.
AB  - Mevalonic aciduria because of mutations of the gene for mevalonate kinase causes
      limited synthesis of isoprenoids, the effects of which are widespread. The
      outcome for affected children is poor. A child with severe multisystem
      manifestations underwent orthotopic liver transplantation at age 50 months for
      the indication of end-stage liver disease. This procedure corrected liver
      function and eliminated portal hypertension, and the patient showed substantial
      improvement in neurological function. However, autoinflammatory episodes
      continued unabated until hematopoietic stem cell transplantation was performed at
      80 months. Through this complex therapy, the patient now enjoys a high quality of
      life without significant disability.

PMID- 22405038
TI  - Noninvasive assessment of the effect of treatment in nonalcoholic fatty liver
      disease: neutrophil to lymphocyte ratio.

PMID- 22405039
TI  - Preliminary investigations of the effect of lipophilic analogues of the active
      metabolite of isoniazid toward bacterial and plasmodial strains.
AB  - Five lipophilic analogues 1-5 of the active metabolite of the antitubercular drug
      isoniazid (INH), selected as inhibitors of Mycobacterium smegmatis and
      Mycobacterium tuberculosis growth, were evaluated for their activity against
      Corynebacterium glutamicum (lacking in InhA activity), Escherichia coli (to test
      mycobacteria selectivity), and Plasmodium falciparum (as possible parasite
      target). Compound 3 was the only one that did not inhibit C. glutamicum growth.
      The poor InhA inhibitors 1 and 2 were able to inhibit C. glutamicum and their
      anti(myco)bacterial mechanisms of action involve targets other than InhA. For the
      effective InhA inhibitors 4 and 5, also active against C. glutamicum and M.
      tuberculosis strains, more than one pathway should be envisaged to explain their
      actions. Pyridine-base ring analogues (1, 2, and 3) have no ability to inhibit
      the growth of E. coli even at a high concentration. Compound 3 thus exhibited a
      selective inhibitory action toward M. tuberculosis, while it was inactive on C.
      glutamicum and on E. coli growth. It presented an activity profile similar to
      that of INH suggesting InhA inhibition as one of the possible mechanisms of
      action. Finally, although a homologue of the reductase InhA exists in the FAS-II
      system of P. falciparum, 3 was unable to display antiplasmodial activity.

PMID- 22405040
TI  - Client consent for clinical research.

PMID- 22405041
TI  - The effect of aging-associated impaired mitochondrial status on kainate-evoked
      hippocampal gamma oscillations.
AB  - Oscillations in hippocampal neuronal networks in the gamma frequency band have
      been implicated in various cognitive tasks and we showed previously that aging
      reduces the power of such oscillations. Here, using submerged hippocampal slices
      allowing simultaneous electrophysiological recordings and imaging, we studied the
      correlation between the kainate-evoked gamma oscillation and mitochondrial
      activity, as monitored by rhodamine 123. We show that the initiation of kainate
      evoked gamma oscillations induces mitochondrial depolarization, indicating a
      metabolic response. Aging had an opposite effect on these parameters: while
      depressing the gamma oscillation strength, it increases mitochondrial
      depolarization. Also, in the aged neurons, kainate induced significantly larger
      Ca2+ signals. In younger slices, acute mitochondrial depolarization induced by
      low concentrations of mitochondrial protonophores strongly, but reversibly,
      inhibits gamma oscillations. These data indicating that the complex network
      activity required by the maintenance of gamma activity is susceptible to changes
      and modulations in mitochondrial status.

PMID- 22405042
TI  - Determinants of cerebellar and cerebral volume in the general elderly population.
AB  - In a population-based study of 3962 community-dwelling nondemented elderly we
      investigated the relation of age, sex, cardiovascular risk factors, and the
      presence of infarcts with cerebellar volume, and its interrelationship with
      cerebral volumes. Cerebellar and cerebral gray and white matter were segmented
      using Freesurfer version 4.5 (http://surfer.nmr.mgh.harvard.edu/). We used linear
      regression analyses to model the relationship between age, sex, cardiovascular
      risk factors, brain infarcts, white matter lesions (WMLs) and cerebellar and
      cerebral volume. Smaller cerebellar volumes with increasing age were mainly
      driven by loss of white matter. Diabetes, higher serum glucose and lower
      cholesterol levels were related to smaller cerebellar volume. No association was
      found between hypertension, smoking, apolipoprotein E (ApoE) genotype, and
      cerebellar volume. Supratentorial lacunar infarcts and WMLs were related to
      smaller cerebellar volume. Infratentorial infarcts were related to smaller
      cerebellar white matter volume and total cerebral volume. This study suggests
      that determinants of cerebellar volume do not entirely overlap with those
      established for cerebral volume. Furthermore, presence of infarcts or WMLs in the
      cerebrum can affect cerebellar volume.

PMID- 22405043
TI  - Gray matter network associated with risk for Alzheimer's disease in young to
      middle-aged adults.
AB  - The apolipoprotein E (APOE) epsilon4 allele increases the risk for late-onset
      Alzheimer's disease (AD) and age-related cognitive decline. We investigated
      whether epsilon4 carriers show reductions in gray matter volume compared with
      epsilon4 non-carriers decades before the potential onset of AD dementia or
      healthy cognitive aging. Fourteen cognitively normal epsilon4 carriers, aged 26
      to 45 years, were compared with 10 age-matched, epsilon4 non-carriers using T1
      weighted volumetric magnetic resonance imaging (MRI) scans. All had reported
      first- or second-degree family histories of dementia. Group differences in gray
      matter were tested using voxel-based morphometry (VBM) and a multivariate model
      of regional covariance, the Scaled Subprofile Model (SSM). A combination of the
      first two SSM MRI gray matter patterns distinguished the APOE epsilon4 carriers
      from non-carriers. This combined pattern showed gray matter reductions in
      bilateral dorsolateral and medial frontal, anterior cingulate, parietal, and
      lateral temporal cortices with covarying relative increases in cerebellum,
      occipital, fusiform, and hippocampal regions. With these gray matter differences
      occurring decades before the potential onset of dementia or cognitive aging, the
      results suggest longstanding, gene-associated differences in brain morphology
      that may lead to preferential vulnerability for the later effects of late-onset
      AD or healthy brain aging.

PMID- 22405044
TI  - Efferent synapses return to inner hair cells in the aging cochlea.
AB  - Efferent innervation of the cochlea undergoes extensive modification early in
      development, but it is unclear if efferent synapses are modified by age, hearing
      loss, or both. Structural alterations in the cochlea affecting information
      transfer from the auditory periphery to the brain may contribute to age-related
      hearing deficits. We investigated changes to efferent innervation in the vicinity
      of inner hair cells (IHCs) in young and old C57BL/6 mice using transmission
      electron microscopy to reveal increased efferent innervation of IHCs in older
      animals. Efferent contacts on IHCs contained focal presynaptic accumulations of
      small vesicles. Synaptic vesicle size and shape were heterogeneous. Postsynaptic
      cisterns were occasionally observed. Increased IHC efferent innervation was
      associated with a smaller number of afferent synapses per IHC, increased outer
      hair cell loss, and elevated auditory brainstem response thresholds. Efferent
      axons also formed synapses on afferent dendrites but with a reduced prevalence in
      older animals. Age-related reduction of afferent activity may engage signaling
      pathways that support the return to an immature state of efferent innervation of
      the cochlea.

PMID- 22405045
TI  - Prediction of Alzheimer's disease using individual structural connectivity
      networks.
AB  - Alzheimer's disease (AD) progressively degrades the brain's gray and white
      matter. Changes in white matter reflect changes in the brain's structural
      connectivity pattern. Here, we established individual structural connectivity
      networks (ISCNs) to distinguish predementia and dementia AD from healthy aging in
      individual scans. Diffusion tractography was used to construct ISCNs with a fully
      automated procedure for 21 healthy control subjects (HC), 23 patients with mild
      cognitive impairment and conversion to AD dementia within 3 years (AD-MCI), and
      17 patients with mild AD dementia. Three typical pattern classifiers were used
      for AD prediction. Patients with AD and AD-MCI were separated from HC with
      accuracies greater than 95% and 90%, respectively, irrespective of prediction
      approach and specific fiber properties. Most informative connections involved
      medial prefrontal, posterior parietal, and insular cortex. Patients with mild AD
      were separated from those with AD-MCI with an accuracy of approximately 85%. Our
      finding provides evidence that ISCNs are sensitive to the impact of earliest
      stages of AD. ISCNs may be useful as a white matter-based imaging biomarker to
      distinguish healthy aging from AD.

PMID- 22405047
TI  - New method for detection of complex 3D fracture motion--verification of an
      optical motion analysis system for biomechanical studies.
AB  - BACKGROUND: Fracture-healing depends on interfragmentary motion. For improved
      osteosynthesis and fracture-healing, the micromotion between fracture fragments
      is undergoing intensive research. The detection of 3D micromotions at the
      fracture gap still presents a challenge for conventional tactile measurement
      systems. Optical measurement systems may be easier to use than conventional
      systems, but, as yet, cannot guarantee accuracy. The purpose of this study was to
      validate the optical measurement system PONTOS 5M for use in biomechanical
      research, including measurement of micromotion. METHODS: A standardized
      transverse fracture model was created to detect interfragmentary motions under
      axial loadings of up to 200 N. Measurements were performed using the optical
      measurement system and compared with a conventional high-accuracy tactile system
      consisting of 3 standard digital dial indicators (1 MUm resolution; 5 MUm error
      limit). RESULTS: We found that the deviation in the mean average motion detection
      between the systems was at most 5.3 MUm, indicating that detection of micromotion
      was possible with the optical measurement system. Furthermore, we could show two
      considerable advantages while using the optical measurement system. Only with the
      optical system interfragmentary motion could be analyzed directly at the fracture
      gap. Furthermore, the calibration of the optical system could be performed
      faster, safer and easier than that of the tactile system. CONCLUSION: The PONTOS
      5 M optical measurement system appears to be a favorable alternative to
      previously used tactile measurement systems for biomechanical applications. Easy
      handling, combined with a high accuracy for 3D detection of micromotions (<= 5
      MUm), suggests the likelihood of high user acceptance. This study was performed
      in the context of the deployment of a new implant (dynamic locking screw;
      Synthes, Oberdorf, Switzerland).

PMID- 22405048
TI  - Intravitreal bevacizumab versus panretinal photocoagulation for treatment-naive
      proliferative and severe nonproliferative diabetic retinopathy.

PMID- 22405049
TI  - Novel molecules for the correction of factor Xa generation and phenotype in
      hemophilia.
AB  - In the intact hemostatic system, the amount of factor Xa needed for efficient
      blood coagulation is supplied by the complex between factors VIIIa and IXa.
      Because hemophilia A patients lack factor VIII and hemophilia B patients lack
      factor IX, they share a bleeding phenotype that has its root in a dramatically
      decreased ability to generate factor Xa. These patients are currently treated by
      replacement therapy with factor VIII and IX, respectively, or, in case they have
      developed neutralizing inhibitory antibodies against the replacing factor, with a
      bypassing agent such as factor VIIa (NovoSeven(r)) or FEIBA(r). This review
      briefly describes a number of novel promising approaches currently in the
      discovery or clinical development phase aiming at increased factor Xa generation
      in hemophilia.

PMID- 22405050
TI  - A review of current methods for assessing hemostasis in vivo and introduction to
      a potential alternative approach.
AB  - A validated method for assessing hemostasis in vivo is critical for testing the
      hemostatic efficacy of therapeutic agents in preclinical animal models and in
      patients with inherited bleeding disorders, such as von Willebrand disease (VWD)
      and hemophilia A, or with acquired bleeding disorders such as those resulting
      from medications or disease processes. In this review, we discuss current methods
      for assessing hemostasis in vivo and the associated challenges. We also present
      ARFI-Monitored Hemostatic Challenge; a new, potentially alternate method for in
      vivo hemostasis monitoring that is in development by our group.

PMID- 22405051
TI  - Imaging coagulation reactions in vivo.
AB  - Significant gaps remain in the understanding of how blood cells and the
      vasculature differentially support coagulation enzyme complex function leading to
      regulated thrombus formation in vivo. While studies employing knock-out or
      transgenic mice have proved useful many of these scientific gaps partly result
      from the lack of molecular approaches and analytic tools with appropriate
      sensitivity for incisive conclusions. Over the past decade, studies employing
      state of the art videomicroscopy to image hemostasis in vivo following laser
      injury to the mouse cremaster arteriole have begun to bridge these gaps and
      provide remarkable insight into the early events of the hemostatic process. Many
      of these new insights have started to question some of the long-standing concepts
      that were driven by in vitro approaches. This review provides an overview of this
      technology, describes insights that have been made using it, and discuss
      limitations and future directions.

PMID- 22405046
TI  - Functional and genetic analysis of haplotypic sequence variation at the nicastrin
      genomic locus.
AB  - Nicastrin (NCSTN) is a component of the gamma-secretase complex and therefore
      potentially a candidate risk gene for Alzheimer's disease. Here, we have
      developed a novel functional genomics methodology to express common locus
      haplotypes to assess functional differences. DNA recombination was used to
      engineer 5 bacterial artificial chromosomes (BACs) to each express a different
      haplotype of the NCSTN locus. Each NCSTN-BAC was delivered to knockout nicastrin
      (Ncstn(-/-)) cells and clonal NCSTN-BAC(+)/Ncstn(-/-) cell lines were created for
      functional analyses. We showed that all NCSTN-BAC haplotypes expressed nicastrin
      protein and rescued gamma-secretase activity and amyloid beta (Abeta) production
      in NCSTN-BAC(+)/Ncstn(-/-) lines. We then showed that genetic variation at the
      NCSTN locus affected alternative splicing in human postmortem brain tissue.
      However, there was no robust functional difference between clonal cell lines
      rescued by each of the 5 different haplotypes. Finally, there was no
      statistically significant association of NCSTN with disease risk in the 4
      cohorts. We therefore conclude that it is unlikely that common variation at the
      NCSTN locus is a risk factor for Alzheimer's disease.

PMID- 22405052
TI  - Does using a femoral nerve block for total knee replacement decrease
      postoperative delirium?
AB  - BACKGROUND: The effect of peripheral nerve blocks on postoperative delirium in
      older patients has not been studied. Peripheral nerve blocks may reduce the
      incidence of postoperative opioid use and its side effects such as delirium via
      opioid-sparing effect. METHODS: A prospective cohort study was conducted in
      patients who underwent total knee replacement. Baseline cognitive function was
      assessed using the Telephone Interview for Cognitive Status. Postoperative
      delirium was measured using the Confusion Assessment Method postoperatively.
      Incidence of postoperative delirium was compared in two postoperative management
      groups: femoral nerve block +/- patient-controlled analgesia and patient
      controlled analgesia only. In addition, pain levels (using numeric rating scales)
      and opioid use were compared in two groups. RESULTS: 85 patients were studied.
      The overall incidence of postoperative delirium either on postoperative day one
      or day two was 48.1%. Incidence of postoperative delirium in the femoral nerve
      block group was lower than patient controlled analgesia only group (25% vs. 61%,
      P = 0.002). However, there was no significant difference between the groups with
      respect to postoperative pain level or the amount of intravenous opioid use.
      CONCLUSIONS: Femoral nerve block reduces the incidence of postoperative delirium.
      These results suggest that a larger randomized control trial is necessary to
      confirm these preliminary findings.

PMID- 22405053
TI  - The independent association between parathyroid hormone levels and hyperuricemia:
      a national population study.
AB  - INTRODUCTION: Increased frequencies of hyperuricemia and gout have been
      associated with primary hyperparathyroidism, and recent clinical trials of
      parathyroid hormone (PTH) have reported hyperuricemic adverse events. We
      evaluated the potential population impact of PTH on serum uric acid (SUA) levels
      by using a nationally representative sample of United States adults. METHODS: By
      using data from 8,316 participants aged 18 years and older in the National Health
      and Nutrition Examination Survey 2003 to 2006, we examined the relation between
      serum PTH and SUA levels with weighted linear regression. Additionally, we
      examined the relation with hyperuricemia by using weighted logistic regression.
      RESULTS: SUA levels increased with increasing serum PTH concentration. After
      adjusting for age, sex, dietary factors, glomerular filtration rate (GFR), and
      other potentially related biomarkers (calcium, phosphorus, alkaline-phosphatase,
      25-hydroxyvitamin D), the SUA level differences from the bottom (referent) to top
      quintiles of serum PTH levels were 0, 8, 13, 14, and 19 MUM (95% CI, 12 to 26; P
      for trend, < 0.001). These estimates were larger among renally impaired
      individuals (multivariate SUA difference between the extreme quintiles of PTH, 26
      versus 15 MUM among those with GFR >= 60 versus < 60 ml/min per 1.73 m2,
      respectively) (P for interaction = 0.004). The odds of hyperuricemia by various
      definitions increased with increasing PTH levels as well (multivariate P values
      for trend, < 0.05). CONCLUSIONS: These nationally representative data indicate
      that serum PTH levels are independently associated with serum uric acid levels
      and the frequency of hyperuricemia at the population level.

PMID- 22405055
TI  - Irrigating methicillin-resistant Staphylococcus aureus-colonised and -infected
      chronic wounds with tap water.

PMID- 22405054
TI  - A new essential protein discovery method based on the integration of protein
      protein interaction and gene expression data.
AB  - BACKGROUND: Identification of essential proteins is always a challenging task
      since it requires experimental approaches that are time-consuming and laborious.
      With the advances in high throughput technologies, a large number of protein
      protein interactions are available, which have produced unprecedented
      opportunities for detecting proteins' essentialities from the network level.
      There have been a series of computational approaches proposed for predicting
      essential proteins based on network topologies. However, the network topology
      based centrality measures are very sensitive to the robustness of network.
      Therefore, a new robust essential protein discovery method would be of great
      value. RESULTS: In this paper, we propose a new centrality measure, named PeC,
      based on the integration of protein-protein interaction and gene expression data.
      The performance of PeC is validated based on the protein-protein interaction
      network of Saccharomyces cerevisiae. The experimental results show that the
      predicted precision of PeC clearly exceeds that of the other fifteen previously
      proposed centrality measures: Degree Centrality (DC), Betweenness Centrality
      (BC), Closeness Centrality (CC), Subgraph Centrality (SC), Eigenvector Centrality
      (EC), Information Centrality (IC), Bottle Neck (BN), Density of Maximum
      Neighborhood Component (DMNC), Local Average Connectivity-based method (LAC), Sum
      of ECC (SoECC), Range-Limited Centrality (RL), L-index (LI), Leader Rank (LR),
      Normalized alpha-Centrality (NC), and Moduland-Centrality (MC). Especially, the
      improvement of PeC over the classic centrality measures (BC, CC, SC, EC, and BN)
      is more than 50% when predicting no more than 500 proteins. CONCLUSIONS: We
      demonstrate that the integration of protein-protein interaction network and gene
      expression data can help improve the precision of predicting essential proteins.
      The new centrality measure, PeC, is an effective essential protein discovery
      method.

PMID- 22405056
TI  - Tailoring of polar and nonpolar ZnO planes on MgO (001) substrates through
      molecular beam epitaxy.
AB  - Polar and nonpolar ZnO thin films were deposited on MgO (001) substrates under
      different deposition parameters using oxygen plasma-assisted molecular beam
      epitaxy (MBE). The orientations of ZnO thin films were investigated by in situ
      reflection high-energy electron diffraction and ex situ X-ray diffraction (XRD).
      The film roughness measured by atomic force microscopy evolved as a function of
      substrate temperature and was correlated with the grain sizes determined by XRD.
      Synchrotron-based X-ray absorption spectroscopy (XAS) was performed to study the
      conduction band structures of the ZnO films. The fine structures of the XAS
      spectra, which were consistent with the results of density functional theory
      calculation, indicated that the polar and nonpolar ZnO films had different
      electronic structures. Our work suggests that it is possible to vary ZnO film
      structures from polar to nonpolar using the MBE growth technique and hence
      tailoring the electronic structures of the ZnO films.PACS: 81; 81.05.Dz;
      81.15.Hi.

PMID- 22405057
TI  - Computational insights into the inhibition of inosine 5'-monophosphate
      dehydrogenase by mycophenolic acid analogs: three-dimensional quantitative
      structure-activity relationship and molecular docking studies.
AB  - Inosine 5'-monophosphate dehydrogenase (IMPDH) is a key enzyme in the de novo
      synthesis of guanosine nucleotides. It is considered as an important target in
      the quest for drugs in the immunosuppressive, antiviral, antibacterial, and
      anticancer therapeutic areas. Herein, we report the 3D-QSAR analyses using
      comparative molecular field analysis (CoMFA), comparative molecular similarity
      indices analysis (CoMSIA) and docking on mycophenolic acid derivates for the
      first time. We obtained cross-validated q(2)  value of 0.805 for CoMFA and 0.620
      for CoMSIA, while the non-cross-validated r(2)  values for them were 0.969 and
      0.935, respectively. Based on the CoMFA and CoMSIA contour maps and docking
      analyses, some key structural factors responsible for inhibitory activity were
      revealed. The results obtained from this study could be used for the rational
      design of potent inhibitors against IMPDH.

PMID- 22405058
TI  - Tolerance and withdrawal of immunosuppressive drugs in patients given kidney and
      hematopoietic cell transplants.
AB  - Sixteen patients conditioned with total lymphoid irradiation (TLI) and
      antithymocyte globulin (ATG) were given kidney transplants and an injection of
      CD34+ hematopoietic progenitor cells and T cells from HLA-matched donors in a
      tolerance induction protocol. Blood cell monitoring included changes in
      chimerism, balance of T-cell subsets and responses to donor alloantigens. Fifteen
      patients developed multilineage chimerism without graft-versus-host disease
      (GVHD), and eight with chimerism for at least 6 months were withdrawn from
      antirejection medications for 1-3 years (mean, 28 months) without subsequent
      rejection episodes. Four chimeric patients have just completed or are in the
      midst of drug withdrawal, and four patients were not withdrawn due to return of
      underlying disease or rejection episodes. Blood cells from all patients showed
      early high ratios of CD4+CD25+ regulatory T cells and NKT cells versus
      conventional naive CD4+ T cells, and those off drugs showed specific
      unresponsiveness to donor alloantigens. In conclusion, TLI and ATG promoted the
      development of persistent chimerism and tolerance in a cohort of patients given
      kidney transplants and hematopoietic donor cell infusions. All 16 patients had
      excellent graft function at the last observation point with or without
      maintenance drugs.

PMID- 22405059
TI  - SFRS10--a splicing factor gene reduced in human obesity?

PMID- 22405061
TI  - Progranulin bridges energy homeostasis and fronto-temporal dementia.

PMID- 22405063
TI  - Supersizing the mitochondrial respiratory chain.
AB  - The complexes of the mitochondrial respiratory chain assemble into higher-order
      structures called supercomplexes or respirasomes that are thought to be important
      in channeling electron flow and controlling ROS production. A number of recent
      papers identify the first protein factors necessary for supercomplex assembly and
      stability.

PMID- 22405064
TI  - Autophagy works out.
AB  - Autophagy is generally considered to be a cytoprotective response to stress,
      whether in the form of nutrient deprivation or the presence of dysfunctional
      organelles. He et al. now show in Nature that exercise-induced autophagy is
      needed for some of the beneficial effects of exercise on metabolism (He et al.,
      2012).

PMID- 22405065
TI  - Irisin, turning up the heat.
AB  - Exercise exerts beneficial effects on systemic metabolism. A recent Nature paper
      (Bostrom et al., 2012) identifies irisin as an exercise-induced hormone secreted
      by skeletal muscle in mice and humans. Irisin promotes brown adipocyte
      recruitment in white fat and improves systemic metabolism by increasing energy
      expenditure.

PMID- 22405067
TI  - Modulation of leptin resistance by protein tyrosine phosphatases.
AB  - Leptin plays a central role in weight control by suppressing food intake and
      increasing energy expenditure. The concept of leptin resistance emerged to
      explain the seemingly paradoxical elevated leptin levels in obesity. Recent
      discoveries reveal that protein tyrosine phosphatases are key players in leptin
      resistance by globally suppressing leptin signaling.

PMID- 22405066
TI  - FAT SIGNALS--lipases and lipolysis in lipid metabolism and signaling.
AB  - Lipolysis is defined as the catabolism of triacylglycerols stored in cellular
      lipid droplets. Recent discoveries of essential lipolytic enzymes and
      characterization of numerous regulatory proteins and mechanisms have
      fundamentally changed our perception of lipolysis and its impact on cellular
      metabolism. New findings that lipolytic products and intermediates participate in
      cellular signaling processes and that "lipolytic signaling" is particularly
      important in many nonadipose tissues unveil a previously underappreciated aspect
      of lipolysis, which may be relevant for human disease.

PMID- 22405068
TI  - 2-arachidonoylglycerol signaling in forebrain regulates systemic energy
      metabolism.
AB  - The endocannabinoid system plays a critical role in the control of energy
      homeostasis, but the identity and localization of the endocannabinoid signal
      involved remain unknown. In the present study, we developed transgenic mice that
      overexpress in forebrain neurons the presynaptic hydrolase, monoacylglycerol
      lipase (MGL), which deactivates the endocannabinoid 2-arachidonoyl-sn-glycerol (2
      AG). MGL-overexpressing mice show a 50% decrease in forebrain 2-AG levels but no
      overt compensation in other endocannabinoid components. This biochemical
      abnormality is accompanied by a series of metabolic changes that include
      leanness, elevated energy cost of activity, and hypersensitivity to beta(3)
      adrenergic-stimulated thermogenesis, which is corrected by reinstating 2-AG
      activity at CB(1)-cannabinoid receptors. Additionally, the mutant mice are
      resistant to diet-induced obesity and express high levels of thermogenic
      proteins, such as uncoupling protein 1, in their brown adipose tissue. The
      results suggest that 2-AG signaling through CB(1) regulates the activity of
      forebrain neural circuits involved in the control of energy dissipation.

PMID- 22405069
TI  - Klf15 orchestrates circadian nitrogen homeostasis.
AB  - Diurnal variation in nitrogen homeostasis is observed across phylogeny. But
      whether these are endogenous rhythms, and if so, molecular mechanisms that link
      nitrogen homeostasis to the circadian clock remain unknown. Here, we provide
      evidence that a clock-dependent peripheral oscillator, Kruppel-like factor 15
      transcriptionally coordinates rhythmic expression of multiple enzymes involved in
      mammalian nitrogen homeostasis. In particular, Kruppel-like factor 15-deficient
      mice exhibit no discernable amino acid rhythm, and the rhythmicity of ammonia to
      urea detoxification is impaired. Of the external cues, feeding plays a dominant
      role in modulating Kruppel-like factor 15 rhythm and nitrogen homeostasis.
      Further, when all behavioral, environmental and dietary cues were controlled in
      humans, nitrogen homeostasis exhibited an endogenous circadian rhythmicity. Thus,
      in mammals, nitrogen homeostasis exhibits circadian rhythmicity, and is
      orchestrated by Kruppel-like factor 15.

PMID- 22405070
TI  - Identification of a protein mediating respiratory supercomplex stability.
AB  - The complexes of the electron transport chain associate into large macromolecular
      assemblies, which are believed to facilitate efficient electron flow. We have
      identified a conserved mitochondrial protein, named respiratory supercomplex
      factor 1 (Rcf1-Yml030w), that is required for the normal assembly of respiratory
      supercomplexes. We demonstrate that Rcf1 stably and independently associates with
      both Complex III and Complex IV of the electron transport chain. Deletion of the
      RCF1 gene caused impaired respiration, probably as a result of destabilization of
      respiratory supercomplexes. Consistent with the hypothetical function of these
      respiratory assemblies, loss of RCF1 caused elevated mitochondrial oxidative
      stress and damage. Finally, we show that knockdown of HIG2A, a mammalian homolog
      of RCF1, causes impaired supercomplex formation. We suggest that Rcf1 is a member
      of an evolutionarily conserved protein family that acts to promote respiratory
      supercomplex assembly and activity.

PMID- 22405071
TI  - Fumarate is cardioprotective via activation of the Nrf2 antioxidant pathway.
AB  - The citric acid cycle (CAC) metabolite fumarate has been proposed to be
      cardioprotective; however, its mechanisms of action remain to be determined. To
      augment cardiac fumarate levels and to assess fumarate's cardioprotective
      properties, we generated fumarate hydratase (Fh1) cardiac knockout (KO) mice.
      These fumarate-replete hearts were robustly protected from ischemia-reperfusion
      injury (I/R). To compensate for the loss of Fh1 activity, KO hearts maintain ATP
      levels in part by channeling amino acids into the CAC. In addition, by
      stabilizing the transcriptional regulator Nrf2, Fh1 KO hearts upregulate
      protective antioxidant response element genes. Supporting the importance of the
      latter mechanism, clinically relevant doses of dimethylfumarate upregulated Nrf2
      and its target genes, hence protecting control hearts, but failed to similarly
      protect Nrf2-KO hearts in an in vivo model of myocardial infarction. We propose
      that clinically established fumarate derivatives activate the Nrf2 pathway and
      are readily testable cytoprotective agents.

PMID- 22405072
TI  - FoxOs integrate pleiotropic actions of insulin in vascular endothelium to protect
      mice from atherosclerosis.
AB  - Atherosclerotic cardiovascular disease is the leading cause of death in insulin
      resistant (type 2) diabetes. Vascular endothelial dysfunction paves the way for
      atherosclerosis through impaired nitric oxide availability, inflammation, and
      generation of superoxide. Surprisingly, we show that ablation of the three genes
      encoding isoforms of transcription factor FoxO in endothelial cells prevents
      atherosclerosis in low-density lipoprotein receptor knockout mice by reversing
      these subphenotypes. Paradoxically, the atheroprotective effect of FoxO deletion
      is associated with a marked decrease of insulin-dependent Akt phosphorylation in
      endothelial cells, owing to reduced FoxO-dependent expression of the insulin
      receptor adaptor proteins Irs1 and Irs2. These findings support a model in which
      FoxO is the shared effector of multiple atherogenic pathways in endothelial
      cells. FoxO ablation lowers the threshold of Akt activity required for protection
      from atherosclerosis. The data demonstrate that FoxO inhibition in endothelial
      cells has the potential to mediate wide-ranging therapeutic benefits for diabetes
      associated cardiovascular disease.

PMID- 22405073
TI  - Pten positively regulates brown adipose function, energy expenditure, and
      longevity.
AB  - Aging in worms and flies is regulated by the PI3K/Akt/Foxo pathway. Here we
      extend this paradigm to mammals. Pten(tg) mice carrying additional genomic copies
      of Pten are protected from cancer and present a significant extension of life
      span that is independent of their lower cancer incidence. Interestingly, Pten(tg)
      mice have an increased energy expenditure and protection from metabolic
      pathologies. The brown adipose tissue (BAT) of Pten(tg) mice is hyperactive and
      presents high levels of the uncoupling protein Ucp1, which we show is a target of
      Foxo1. Importantly, a synthetic PI3K inhibitor also increases energy expenditure
      and hyperactivates the BAT in mice. These effects can be recapitulated in
      isolated brown adipocytes and, moreover, implants of Pten(tg) fibroblasts
      programmed with Prdm16 and Cebpbeta form subcutaneous brown adipose pads more
      efficiently than wild-type fibroblasts. These observations uncover a role of Pten
      in promoting energy expenditure, thus decreasing nutrient storage and its
      associated damage.

PMID- 22405075
TI  - Acute exercise remodels promoter methylation in human skeletal muscle.
AB  - DNA methylation is a covalent biochemical modification controlling chromatin
      structure and gene expression. Exercise elicits gene expression changes that
      trigger structural and metabolic adaptations in skeletal muscle. We determined
      whether DNA methylation plays a role in exercise-induced gene expression. Whole
      genome methylation was decreased in skeletal muscle biopsies obtained from
      healthy sedentary men and women after acute exercise. Exercise induced a dose
      dependent expression of PGC-1alpha, PDK4, and PPAR-delta, together with a marked
      hypomethylation on each respective promoter. Similarly, promoter methylation of
      PGC-1alpha, PDK4, and PPAR-delta was markedly decreased in mouse soleus muscles
      45 min after ex vivo contraction. In L6 myotubes, caffeine exposure induced gene
      hypomethylation in parallel with an increase in the respective mRNA content.
      Collectively, our results provide evidence that acute gene activation is
      associated with a dynamic change in DNA methylation in skeletal muscle and
      suggest that DNA hypomethylation is an early event in contraction-induced gene
      activation.

PMID- 22405074
TI  - PPARgamma agonists induce a white-to-brown fat conversion through stabilization
      of PRDM16 protein.
AB  - Brown adipose tissue dissipates energy through heat and functions as a defense
      against cold and obesity. PPARgamma ligands have been shown to induce the
      browning of white adipocytes; however, the underlying mechanisms remain unclear.
      Here, we show that PPARgamma ligands require full agonism to induce a brown fat
      gene program preferentially in subcutaneous white adipose. These effects require
      expression of PRDM16, a factor that controls the development of classical brown
      fat. Depletion of PRDM16 blunts the effects of the PPARgamma agonist
      rosiglitazone on the induced brown fat gene program. Conversely, PRDM16 and
      rosiglitazone synergistically activate the brown fat gene program in vivo. This
      synergy is tightly associated with an increased accumulation of PRDM16 protein,
      due in large measure to an increase in the half-life of the protein in agonist
      treated cells. Identifying compounds that stabilize PRDM16 protein may represent
      a plausible therapeutic pathway for the treatment of obesity and diabetes.

PMID- 22405076
TI  - Liver stiffness correlates with Child-Pugh-Turcotte and MELD scores in
      HIV/hepatitis C virus-coinfected patients with cirrhosis.

PMID- 22405077
TI  - The Lewis GFP transgenic rat strain is a useful cell donor for neural
      transplantation.
AB  - Stem cell transplantation is a promising therapeutic approach in
      neurodegenerative diseases. Studying graft survival and development has important
      implications for the further development of experimental and clinical
      transplantation protocols. Cellular elements in neural transplants  are sometimes
      difficult to identify. The existing labeling methods cannot reliably provide
      stably labeled cells that can be detected in long-term experiments. Transgenic
      (tg) Lewis rats ubiquitously expressing green fluorescent protein (GFP) provide
      an ideal donor source. The aim of this project  was to investigate the potential
      of GFP-tg Lewis rats to serve as donor tissue for neural stem cell
      transplantation. Ventral mesencephalon (VM) GFP-tg E14.5-derived cells were
      compared to wild-type (wt) in vitro and in vivo. Firstly, cells from GFP and non
      GFP VM tissue were compared with  regard to their proliferation and response
      towards 6-OHDA-toxicity in culture. Secondly, 6-OHDA-lesioned hemiparkinsonian
      Sprague-Dawley/Crl:CD(SD) rats received intrastriatal grafts derived from VM of
      E14.5 GFP-tg rats. Due to the fact that donor and recipient belong to two
      different rat  strains, we focused on graft survival in correlation with
      immunosuppression and graft GFP and tyrosine hydroxylase (TH) expression. In
      summary, in vitro tg cells exhibited 98% GFP expression and did not differ from
      wt cells in any of the measured parameters. In vivo, all experimental groups 
      showed a significant compensation in rotation behavior after transplantation.
      Furthermore, there was no difference on rotation behavior or graft morphology and
      survival pattern as well as GFP expression between immunosuppressed and
      nonimmunosuppressed animals. The GFP-positive population of  the graft was
      composed of 13.3% GFAP-positive, 56.1% NeuN-positive, and 1.9% TH-positive cells.
      Analysis of graft subpopulations manifested that 70.6% of GFAP-positive, 86.9% of
      NeuN-positive, and 80.1% of TH-positive cells coexpressed GFP. In conclusion, our
      data show that the Lewis GFP-tg  rats serve as an excellent cell source for
      studying primary neural precursor cells in the transplantation paradigm.

PMID- 22405078
TI  - Ultrasonic reflection coefficient and surface roughness index of OA articular
      cartilage: relation to pathological assessment.
AB  - BACKGROUND: Early diagnosis of osteoarthritis (OA) is essential for preventing
      further cartilage destruction and decreasing severe complications. The aims of
      this study are to explore the relationship between OA pathological grades and
      quantitative acoustic parameters and to provide more objective criteria for
      ultrasonic microscopic evaluation of the OA cartilage. METHODS: Articular
      cartilage samples were prepared from rabbit knees and scanned using ultrasound
      biomicroscopy (UBM). Three quantitative parameters, including the roughness index
      of the cartilage surface (URI), the reflection coefficients from the cartilage
      surface (R) and from the cartilage-bone interface (Rbone) were extracted. The
      osteoarthritis grades of these cartilage samples were qualitatively assessed by
      histology according to the grading standards of International Osteoarthritis
      Institute (OARSI). The relationship between these quantitative parameters and the
      osteoarthritis grades was explored. RESULTS: The results showed that URI
      increased with the OA grade. URI of the normal cartilage samples was
      significantly lower than the one of the OA cartilage samples. There was no
      significant difference in URI between the grade 1 cartilage samples and the grade
      2 cartilage samples. The reflection coefficient of the cartilage surface reduced
      significantly with the development of OA (p < 0.05), while the reflection
      coefficient of the cartilage-bone interface increased with the increase of grade.
      CONCLUSION: High frequency ultrasound measurements can reflect the changes in the
      surface roughness index and the ultrasound reflection coefficients of the
      cartilage samples with different OA grades. This study may provide useful
      information for the quantitative ultrasonic diagnosis of early OA.

PMID- 22405079
TI  - Thoracic epidural analgesia via the lumbosacral approach using multiport
      catheters with a low concentration of bupivacaine and morphine in sheep.
AB  - OBJECTIVE: To determine the analgesic and systemic effects of thoracic epidural
      administration of bupivacaine (BP) and morphine (MP) in conscious sheep. STUDY
      DESIGN: Randomized, crossover, experimental study. ANIMALS: Six healthy castrated
      sheep weighing between 40 and 50 kg. METHODS: Each sheep received, via the
      lumbosacral approach, BP (0.5 mg kg(-1)), MP (0.1 mg kg(-1)), and BP plus MP
      (BPMP; 0.25 mg kg(-1) + 0.05 mg kg(-1)) in a randomized order. Heart rate, blood
      pressure, respiratory rate, blood gas analysis, skin temperature, rectal
      temperature, analgesia, sedation, and motor blockade were determined before
      treatment and at predetermined intervals until analgesia had disappeared.
      RESULTS: The main areas of complete analgesia for the BP and BPMP treatments were
      the thorax and forelimb bilaterally. The median duration of analgesia was shorter
      with MP treatment (45 minutes; score 2) than with BP treatment (70 minutes) and
      BPMP treatment (140 minutes; p < 0.05). The BP and BPMP treatments caused motor
      block, and MP and BPMP treatments showed mild sedation. Significant decreases in
      systolic and diastolic arterial blood pressures were observed only with the BP
      treatment (p < 0.05). Epidural MP combined with the BP local anesthetic depressed
      ventilation but within acceptable limits in these clinically healthy sheep.
      CONCLUSIONS: Thoracic epidural administration of BPMP to sheep resulted in longer
      duration of analgesia of the thorax and forelimbs bilaterally in conscious sheep
      than the administration of MP or BP alone. The incidence of complications was
      low, but side-effects such as depressed ventilation and muscle paralysis occurred
      and require appropriate management. CLINICAL RELEVANCE: This technique should be
      considered as another method for the relief of postoperative pain after thoracic
      surgery in sheep.

PMID- 22405080
TI  - Retinal vessel diameter in young patients with open-angle glaucoma: comparison
      between high-tension and normal-tension glaucoma.

PMID- 22405082
TI  - 2011 Presidential Address: from classroom to courtroom to clinic-closing the gaps
      in human genetics education.

PMID- 22405083
TI  - 2011 William Allan Award introduction: John M. Opitz.

PMID- 22405084
TI  - 2011 William Allan Award: development and evolution.

PMID- 22405085
TI  - 2011 introduction to Curt Stern Award.

PMID- 22405086
TI  - 2011 Curt Stern Award address.

PMID- 22405087
TI  - Infantile cerebellar-retinal degeneration associated with a mutation in
      mitochondrial aconitase, ACO2.
AB  - Degeneration of the cerebrum, cerebellum, and retina in infancy is part of the
      clinical spectrum of lysosomal storage disorders, mitochondrial respiratory chain
      defects, carbohydrate glycosylation defects, and infantile neuroaxonal dystrophy.
      We studied eight individuals from two unrelated families who presented at 2-6
      months of age with truncal hypotonia and athetosis, seizure disorder, and
      ophthalmologic abnormalities. Their course was characterized by failure to
      acquire developmental milestones and culminated in profound psychomotor
      retardation and progressive visual loss, including optic nerve and retinal
      atrophy. Despite their debilitating state, the disease was compatible with
      survival of up to 18 years. Laboratory investigations were normal, but the
      oxidation of glutamate by muscle mitochondria was slightly reduced. Serial brain
      MRI displayed progressive, prominent cerebellar atrophy accompanied by thinning
      of the corpus callosum, dysmyelination, and frontal and temporal cortical
      atrophy. Homozygosity mapping followed by whole-exome sequencing disclosed a
      Ser112Arg mutation in ACO2, encoding mitochondrial aconitase, a component of the
      Krebs cycle. Specific aconitase activity in the individuals' lymphoblasts was
      severely reduced. Under restrictive conditions, the mutant human ACO2 failed to
      complement a yeast ACO1 deletion strain, whereas the wild-type human ACO2
      succeeded, indicating that this mutation is pathogenic. Thus, a defect in
      mitochondrial aconitase is associated with an infantile neurodegenerative
      disorder affecting mainly the cerebellum and retina. In the absence of
      noninvasive biomarkers, determination of the ACO2 sequence or of aconitase
      activity in lymphoblasts are warranted in similarly affected individuals, based
      on clinical and neuroradiologic grounds.

PMID- 22405088
TI  - Exome sequencing reveals mutations in TRPV3 as a cause of Olmsted syndrome.
AB  - Olmsted syndrome (OS) is a rare congenital disorder characterized by palmoplantar
      and periorificial keratoderma, alopecia in most cases, and severe itching. The
      genetic basis for OS remained unidentified. Using whole-exome sequencing of case
      parents trios, we have identified a de novo missense mutation in TRPV3 that
      produces p.Gly573Ser in an individual with OS. Nucleotide sequencing of five
      additional affected individuals also revealed missense mutations in TRPV3 (which
      produced p.Gly573Ser in three cases and p.Gly573Cys and p.Trp692Gly in one case
      each). Encoding a transient receptor potential vanilloid-3 cation channel, TRPV3
      is primarily expressed in the skin, hair follicles, brain, and spinal cord. In
      transfected HEK293 cells expressing TRPV3 mutants, much larger inward currents
      were recorded, probably because of the constitutive opening of the mutants. These
      gain-of-function mutations might lead to elevated apoptosis of keratinocytes and
      consequent skin hyperkeratosis in the affected individuals. Our findings suggest
      that TRPV3 plays essential roles in skin keratinization, hair growth, and
      possibly itching sensation in humans and selectively targeting TRPV3 could
      provide therapeutic potential for keratinization or itching-related skin
      disorders.

PMID- 22405089
TI  - Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling
      complex, is a frequent cause of intellectual disability.
AB  - Intellectual disability (ID) is a clinically and genetically heterogeneous common
      condition that remains etiologically unresolved in the majority of cases.
      Although several hundred diseased genes have been identified in X-linked,
      autosomal-recessive, or syndromic types of ID, the establishment of an
      etiological basis remains a difficult task in unspecific, sporadic cases. Just
      recently, de novo mutations in SYNGAP1, STXBP1, MEF2C, and GRIN2B were reported
      as relatively common causes of ID in such individuals. On the basis of a patient
      with severe ID and a 2.5 Mb microdeletion including ARID1B in chromosomal region
      6q25, we performed mutational analysis in 887 unselected patients with
      unexplained ID. In this cohort, we found eight (0.9%) additional de novo nonsense
      or frameshift mutations predicted to cause haploinsufficiency. Our findings
      indicate that haploinsufficiency of ARID1B, a member of the SWI/SNF-A chromatin
      remodeling complex, is a common cause of ID, and they add to the growing evidence
      that chromatin-remodeling defects are an important contributor to
      neurodevelopmental disorders.

PMID- 22405090
TI  - Multiple imputation for estimating hazard ratios and predictive abilities in case
      cohort surveys.
AB  - BACKGROUND: The weighted estimators generally used for analyzing case-cohort
      studies are not fully efficient and naive estimates of the predictive ability of
      a model from case-cohort data depend on the subcohort size. However, case-cohort
      studies represent a special type of incomplete data, and methods for analyzing
      incomplete data should be appropriate, in particular multiple imputation (MI).
      METHODS: We performed simulations to validate the MI approach for estimating
      hazard ratios and the predictive ability of a model or of an additional variable
      in case-cohort surveys. As an illustration, we analyzed a case-cohort survey from
      the Three-City study to estimate the predictive ability of D-dimer plasma
      concentration on coronary heart disease (CHD) and on vascular dementia (VaD)
      risks. RESULTS: When the imputation model of the phase-2 variable was correctly
      specified, MI estimates of hazard ratios and predictive abilities were similar to
      those obtained with full data. When the imputation model was misspecified, MI
      could provide biased estimates of hazard ratios and predictive abilities. In the
      Three-City case-cohort study, elevated D-dimer levels increased the risk of VaD
      (hazard ratio for two consecutive tertiles = 1.69, 95%CI: 1.63-1.74). However, D
      dimer levels did not improve the predictive ability of the model. CONCLUSIONS: MI
      is a simple approach for analyzing case-cohort data and provides an easy
      evaluation of the predictive ability of a model or of an additional variable.

PMID- 22405091
TI  - Escape of Mycobacterium tuberculosis from oxidative killing by neutrophils.
AB  - Neutrophils enter sites of infection, where they can eliminate pathogenic
      bacteria in an oxidative manner. Despite their predominance in active
      tuberculosis lesions, the function of neutrophils in this important human
      infection is still highly controversial. We observed that virulent Mycobacterium
      tuberculosis survived inside human neutrophils despite prompt activation of these
      defence cells' microbicidal effectors. Survival of M. tuberculosis was
      accompanied by necrotic cell death of infected neutrophils. Necrotic cell death
      entirely depended on radical oxygen species production since chronic
      granulomatous disease neutrophils were protected from M. tuberculosis-triggered
      necrosis. More, importantly, the M. tuberculosis DeltaRD1 mutant failed to induce
      neutrophil necrosis rendering this strain susceptible to radical oxygen species
      mediated killing. We conclude that this virulence function is instrumental for M.
      tuberculosis to escape killing by neutrophils and contributes to pathogenesis in
      tuberculosis.

PMID- 22405093
TI  - Cardiac arrest due to lymphocytic colitis: a case report.
AB  - INTRODUCTION: We present a case of cardiac arrest due to hypokalemia caused by
      lymphocytic colitis. CASE PRESENTATION: A 69-year-old Caucasian man presented
      four months prior to a cardiac arrest with watery diarrhea and was diagnosed with
      lymphocytic colitis. Our patient experienced a witnessed cardiac arrest at his
      general practitioner's surgery. Two physicians and the emergency medical services
      resuscitated our patient for one hour and four minutes before arriving at our
      university hospital. Our patient was defibrillated 16 times due to the recurrence
      of ventricular tachyarrhythmias. An arterial blood sample revealed a potassium
      level of 2.0 mmol/L (reference range: 3.5 to 4.6 mmol/L) and pH 6.86 (reference
      range: pH 7.37 to 7.45). As the potassium level was corrected, the propensity for
      ventricular tachyarrhythmias ceased. Our patient recovered from his cardiac
      arrest without any neurological deficit. Further tests and examinations revealed
      no other reason for the cardiac arrest. CONCLUSION: Diarrhea can cause life
      threatening situations due to the excretion of potassium, ultimately causing
      cardiac arrest due to hypokalemia. Physicians treating patients with severe
      diarrhea should consider monitoring their electrolyte levels.

PMID- 22405092
TI  - Immunohistochemical detection of Polo-like kinase-1 (PLK1) in primary breast
      cancer is associated with TP53 mutation and poor clinical outcom.
AB  - INTRODUCTION: Polo-like kinase-1 (PLK1) is a crucial driver of cell cycle
      progression and its down-regulation plays an important checkpoint role in
      response to DNA damage. Mechanistically, this is mediated by p53 which represses
      PLK1 expression through chromatin remodelling. Consistent with this model,
      cultured cells lacking p53 fail to repress PLK1 expression. This study examined
      PLK1 expression, p53 mutation and clinical outcome in breast cancer. METHODS:
      Immunohistochemistry was performed using antibodies to PLK1, MDM2 and Ki67 on
      Tissue Micro-Array (TMA) slides of a cohort of 215 primary breast cancers. The
      TP53 gene (encoding p53) was sequenced in all tumour samples. Protein expression
      scored using the "Quickscore" method was compared with clinical and pathological
      data, including survival. RESULTS: Staining of PLK1 was observed in 11% of
      primary breast tumours and was significantly associated with the presence of TP53
      mutation (P = 0.0063). Moreover, patients with both PLK1 expression and TP53
      mutation showed a significantly worse survival than those with either PLK1
      expression or TP53 mutation alone. There was also a close association of elevated
      PLK1 with triple negative tumours, considered to be poor prognosis breast cancers
      that generally harbour TP53 mutation. Further association was observed between
      elevated PLK1 levels and the major p53 negative regulator, MDM2. CONCLUSIONS: The
      significant association between elevated PLK1 and TP53 mutation in women with
      breast cancer is consistent with escape from repression of PLK1 expression by
      mutant p53. Tumours expressing elevated PLK1, but lacking functional p53, may be
      potential targets for novel anti-PLK1-targeted drugs.

PMID- 22405094
TI  - Efficacy and safety of a gauze pad containing hyaluronic acid in treatment of leg
      ulcers of venous or mixed origin: a double-blind, randomised, controlled trial.
AB  - Topical hyaluronic acid (HA) is routinely used in the local treatment of chronic
      wounds, but few data have been reported to date. A 60-day double-blind,
      randomised, controlled superiority trial was designed to investigate the efficacy
      and safety of a gauze pad containing HA in local treatment of venous leg ulcers,
      compared with its neutral vehicle. The primary endpoint was the percentage of
      wound size reduction after 45 days. Totally 89 patients were included. At day 45,
      the percentage of ulcer surface reduction was significantly greater in the HA
      group (73 +/- 4.6%) versus neutral vehicle group (46 +/- 9.6%) (P = 0.011). The
      number of healed ulcers was significantly higher in the HA group at day 45 (31.1%
      versus 9.3% respectively) and day 60 (37.8% versus 16.3% respectively; P < 0.05).
      At day 30, pain intensity based on visual analogue scale was significantly lower
      in the HA group (12.4 mm +/- 2.6 versus 22.8 mm +/- 3.8; P = 0.026). Tolerance of
      both treatments was comparable in the two groups. HA gauze pad, in local
      treatment of venous leg ulcers, was significantly more effective than the neutral
      vehicle on wound size reduction, healed ulcers rate and pain management with a
      good safety profile.

PMID- 22405095
TI  - The relationship between accelerometer-determined physical activity (PA) and body
      composition and bone mineral density (BMD) in postmenopausal women.
AB  - Studies of the relationships between BMD, PA and body composition have shown
      variable results. Therefore, the aim of this cross-sectional study was to
      determine the relationships between accelerometer-determined PA and selected body
      composition parameters to total and regional BMD of the proximal femur in
      postmenopausal women. BMD and body composition were measured using dual energy X
      ray absorptiometry in 97 women with a mean age 63.63+/-5.23 years. PA was
      monitored using an ActiGraph GT1M accelerometer. Correlation analysis did not
      show significant relationships between PA variables and BMD, but increases in
      body composition variables were associated with increases in BMD. Lean body mass
      was the strongest predictor of proximal femur BMD (r=0.18-0.37), explaining 10%
      of the variance for total femur, and 3-14% of the variance for regional femurs.
      Correlations increased when the analysis was controlled for age (r(p)=0.20-0.39).
      A significant relationship was also found between body fat mass and BMD (r=0.16
      0.30; r(p)=0.25-0.37). Analysis of differences between women with normal BMD and
      osteopenic women showed statistically significant differences in age (p=0.003;
      eta(2)=0.09) and lean body mass (p=0.048; eta(2)=0.04). In conclusion, body
      composition is a stronger predictor of proximal femur BMD than PA variables.
      However, other studies are necessary to clarify the influence of long-term PA and
      exercise type on proximal femur BMD.

PMID- 22405096
TI  - Graphite flake self-retraction response based on potential seeking.
AB  - The high elastic modulus and interlayer strengths of graphite flakes make them a
      durable solid superlubricant. Apart from this, they have configurable electrical
      properties, exhibit quantum Hall effects, and possess a myriad of useful photonic
      properties. The self-retraction behavior of graphite flakes can have significant
      impact on the creation of ordered stacks for various applications because any
      accidental or intentional displacement of the top flake over the stacks below may
      result in a misalignment of the carbon-carbon atomic arrangement which, in turn,
      can have influence over the electrical and photonic properties. It has also been
      revealed that there was a tendency of the displaced microflake to fail at times
      to return to its original starting position and orientation. Here, we elucidate
      this behavior by considering the influence of the interlayer potential forces
      based on minimal potential energy seeking. The maps of the parameters
      interrogated here provide the ability for precautions to be undertaken. They also
      potentially permit the creation of an array of microflake stacks in which the
      metastable states permit different information to be encoded by virtue of the
      differentiated photonic or electrical characteristics readable from each array
      site.

PMID- 22405097
TI  - [The most read Spanish medical journals in primary care].

PMID- 22405098
TI  - [Stratification of the population in the Basque Country: results in the first
      year of implementation].
AB  - Predictive models allow populations to be stratified according to their health
      requirements for the following year. They offer health care organizations the
      opportunity to act proactively, designing specific interventions adapted to the
      level of need of different groups of people. The "Strategy for tackling the
      challenge of chronic illness in the Basque Country" proposes the use of such
      models, integrating them with other policies. The prospective categorization of
      all the population assigned to Osakidetza was performed for the first time in
      2010 using the Johns Hopkins Adjusted Clinical Groups predictive model (ACG-PM).
      For this purpose, already recorded information extracted from electronic health
      records of primary care and hospital discharge reports was used. This article
      discusses the advantages of the combined use of various sources of information,
      and describes the application of the stratification in three programs, targeted
      at chronic patients who suffer different burdens of comorbidity.

PMID- 22405099
TI  - Bone healing after tooth extraction with or without an intervention: a systematic
      review of randomized controlled trials.
AB  - OBJECTIVES: To assess whether the use of a graft and/or membrane post-tooth
      extraction improves healing of the site dimensionally, radiographically, and/or
      histologically. MATERIALS AND METHODS: MEDLINE and EMBASE and the Cochrane
      Central register of controlled trials (CENTRAL) were searched up until August
      2011. Randomized controlled trials that included and compared healing post-tooth
      extraction between a control (no intervention) and a graft and/or membrane (test)
      were selected. RESULTS: Titles and abstracts of 2,861 papers were screened. A
      total of 42 papers were selected for full text reading. Nine papers met the
      eligibility criteria and were selected for further analysis. Because of the
      varying graft materials used and the different methods of investigation, as well
      as the variation in follow-up times, a meta-analysis was not possible. The
      present review found that clinically, there was a range in loss of width in the
      control sites of 2.46 mm (SD 0.4 mm) to 4.56 mm (SD 0.33 mm) compared to 1.14 mm
      (SD 0.87 mm) to 2.5 mm (SD 1.2 mm) in the test sites. The range in loss of height
      in control sites was 0.9 mm (SD 1.6 mm) to 3.6 mm (SD 1.5 mm) compared to a gain
      of 1.3 mm (SD 2 mm) to a loss of 0.62 mm (SD 0.51 mm) in test sites.
      Radiographically a range of change in bone height of between 0.51 mm (No SD) to
      1.17 mm (SD 1.23 mm) was noted in control sites compared to a change of between
      0.02 mm (SD 1.2 mm) and 1 mm (SD 1.4 mm) in test sites. CONCLUSION: There is
      limited data regarding the effectiveness of alveolar ridge preservation therapies
      when compared to the control. Overall the socket intervention therapies did
      reduce alveolar ridge dimensional changes post-extraction, but were unable to
      prevent resorption. Histology did demonstrate a large proportion of residual
      graft material that may account for some of the difference in alveolar ridge
      dimensions at follow up.

PMID- 22405100
TI  - Structure-activity relationship study of collagen-derived anti-angiogenic
      biomimetic peptides.
AB  - Structure-activity relationship (SAR) studies are essential in the generation of
      peptides with enhanced activity and efficacy as therapeutic agents. In this
      study, we report a Structure-activity relationship study for a family of mimetic
      peptides derived from type IV collagen with potent anti-angiogenic properties.
      The Structure-activity relationship study was conducted using a number of
      validated in vitro assays including cell proliferation, adhesion, migration, and
      tubule formation. We report a critical sequence (NINNV) within this peptide
      series, which is required for the potent anti-angiogenic activity. Detailed amino
      acid substitutions resulted in peptides with superior efficacy. Specifically,
      substitutions with isoleucine at positions 12 and 18 along with the substitution
      of the methionine at position 10 with the non-natural amino acid D-alanine led to
      an increase in potency by two orders of magnitude over the parent peptide.
      Several mimetic peptides in this series exhibit a significant improvement of
      activity over the parent peptide. This improved in vitro activity is expected to
      correlate with an increase in in vivo activity leading to effective peptides for
      anti-angiogenic therapy for different disease applications including cancer and
      age-related macular degeneration.

PMID- 22405101
TI  - Morphometric characteristics of basal cell carcinoma peritumoral stroma varies
      among basal cell carcinoma subtypes.
AB  - BACKGROUND: The role that the peritumoral stroma plays in the growth of tumours
      is currently poorly understood. In this manuscript the morphometric
      characteristics of basal cell carcinoma subtypes and their associated peritumoral
      stromas are presented. METHODS: Ninety eight digitized basal cell carcinoma
      histology slides were categorized as infiltrative, nodular, or superficial
      subtypes, and were analysed using a combination of manual and computer-assisted
      approaches. The morphometric characteristics of the tumour nests and their
      associated peritumoral stroma were quantified, and the presence of a marked
      immune reaction or elastosis was noted. RESULTS: The tumour to stroma ratio was
      different among each tumour subtype. Elastosis was identified in a greater
      proportion of the infiltrative tumours. CONCLUSIONS: Quantitative differences
      exist between the peritumoral stroma of basal cell carcinoma subtypes. Future
      work exploring the relation between these morphometric differences and
      biochemical variations in peritumoral stroma may further our understanding of the
      biology of carcinoma development. TRIAL REGISTRATION: Not applicable.

PMID- 22405102
TI  - [Asthma triggered by food].

PMID- 22405103
TI  - [Small airways: a therapeutic target in cystic fibrosis?].

PMID- 22405104
TI  - [High frequency percussion ventilation: indications need to be more precisely
      defined].

PMID- 22405105
TI  - [Aerosolstorming: the GAT workshop on inhalation therapy].

PMID- 22405106
TI  - [The role of FDG PET-CT in stage IIIA non-small cell lung carcinoma in 2012].

PMID- 22405107
TI  - [Physiopathology of aspirin intolerant asthma].
AB  - Aspirin-exacerbated respiratory disease (AERD) refers to the development of
      bronchoconstriction in individuals with asthma following the ingestion of
      aspirin. AERD affects up to 20 % of adults with asthma. At present, no reliable
      in vitro test is available to confirm the diagnosis. The confirmation of the
      diagnosis of AERD therefore depends on the response to challenge testing with
      aspirin. The pathogenesis of AERD is linked to abnormalities in arachidonic acid
      metabolism. Prior to exposure to aspirin, respiratory mucosal inflammation is the
      result of a cell infiltration, an overproduction of leukotrienes, prostaglandins
      D2, 5-oxo-eicosatetraenoic acid and an underproduction of lipoxins. After aspirin
      ingestion, patients with AERD synthesize excessive amounts of cysteinyl
      leukotrienes and prostaglandin metabolites involved in bronchoconstriction. New
      hypotheses concerning AERD pathogenesis have been added to the initial
      cyclooxygenase theory. These propose that AERD may be linked to the complement
      system, adenosine metabolism or angiotensin converting enzyme gene and IgE
      receptor gene polymorphisms.

PMID- 22405108
TI  - [Cystic fibrosis: instrumental airway clearance techniques].
AB  - INTRODUCTION: Chest physiotherapy is an essential part of the life-long
      therapeutic routine in patients with cystic fibrosis. STATE OF THE ART: Various
      manoeuvres are available but there is no consensus supporting one specific
      technique over others. These techniques can be classified as "manual" or
      "instrumental". Instrumental airway clearance techniques are based on
      physiological principles and consist in the application of vibrations or positive
      expiratory pressure during expiratory phase to enhance sputum clearance. Positive
      expiratory pressure can be delivered continuously or in an oscillating pattern.
      The effects of these devices have been investigated in many studies.
      PERSPECTIVES: Results suggest a potential place for these techniques in the
      management of cystic fibrosis, but they remain poorly used. CONCLUSION: A better
      knowledge of these approaches could enable them to integrate more widely into the
      physiotherapy management of patients with cystic fibrosis.

PMID- 22405109
TI  - [Management of anterior mediastinal masses in adults].
AB  - The discovery of an anterior mediastinal mass requires careful management with
      specific consideration of the pathology. More than 50% of all mediastinal masses
      seen in adults are in the anterior mediastinum. The most frequent diagnoses are
      thymoma, lymphoma, teratoma and benign thyroid tumours. 60% of cases are
      malignant. Often the clinical and radiological findings do not allow a definitive
      diagnosis and a histological diagnosis is often required to select the optimal
      treatment modality. The choice of biopsy technique depends on the localization of
      the lesion, clinical factors, and the availability of special techniques and
      equipment. Biopsy may be obtained by trans-thoracic puncture under computed
      tomography or ultrasound guidance, or by a surgical approach (mediastinotomy or
      thoracoscopy).

PMID- 22405110
TI  - [Role of FDG-PET scanning in stage IIIAN2 non-small cell lung cancer].
AB  - Patients with clinical stage IIIAN2 non-small cell lung cancer (NSCLC) are a
      heterogeneous subgroup in term of prognosis and therapeutic management. The
      optimal management of this patient group is a major focus for thoracic oncology
      research and the concept of multimodality treatment has recently been introduced.
      This approach combines induction chemotherapy or radiochemotherapy followed by
      surgery in the case of mediastinal lymph node down-staging. positron emission
      tomography computed tomography with [18F]-fluorodesoxyglucose (FDG-PET) is a
      molecular and metabolic imaging modality which combines the metabolic data of PET
      with morphological data from CT. FDG-PET has become a standard in lung cancer
      management since the different indications listed in the standards, options and
      recommendations (SOR) of the FNCLCC. However, the potential specific importance
      of FDG-PET in IIIAN2 patients needs to be addressed further. In this setting, the
      authors' objective is to review the potential role of metabolic imaging in stage
      IIIAN2 NSCLC, taking into account new multimodality treatments. In stage IIIAN2,
      FDG-PET has performed better than morphoradiological imaging for baseline and
      postinduction lymph node staging, the identification of distant metastasis, and
      determining prognosis, as well as assessing the response to treatment.

PMID- 22405111
TI  - [Anti-angiogenic agents in the treatment of lung cancer: indications and
      toxicities].
AB  - Lung cancer is the leading cause of cancer-related death. Targeting the vascular
      endothelial growth factor (VEGF) pathways in combination with standard
      chemotherapy can improve response rate and survival in non-small cell lung
      cancer. Since October 2006, a new class of drugs targeting angiogenesis has been
      introduced for the treatment of advanced lung cancer. Bevacizumab, an antibody
      directly targeting VEGF was the first agent to be approved. Other small molecule
      tyrosine kinase inhibitors targeting the VEGF receptor are also active in the
      treatment of advanced lung cancer and are currently under development. Most of
      these new drugs are well tolerated though potentially significant toxicities such
      as haemoptysis and hypertension have been observed. This article will review
      these new-targeted anti-angiogenic agents with a focus on their use in lung
      cancer and on their important side effects.

PMID- 22405112
TI  - [Indications for intrapulmonary percussive ventilation (IPV): a review of the
      literature].
AB  - INTRODUCTION: Intrapulmonary Percussive Ventilation (IPV) is used to treat
      peripheral airway obstruction as well as disorders of ventilation. STATE OF THE
      ART: The medical literature shows that IPV can be deployed for both symptomatic
      and prophylactic purposes. When conventional techniques of chest physiotherapy
      have been ineffective, IPV may be delivered in a variety of severe respiratory
      diseases via both invasive and non-invasive interfaces. Diseases such as advanced
      neuromuscular disorders with severe bronchial congestion, stable or decompensated
      cystic fibrosis and chronic obstructive pulmonary disease whether in the stable
      condition, during exacerbations or after extubation as well as atelectasis or
      other severe respiratory complications may all benefit from therapeutic effects
      of IPV. Very few contra-indications are reported in the literature. PERSPECTIVES:
      The precise physiological effects of IPV are not yet well demonstrated. Despite
      significant progresses, the level of evidence for the clinical effectiveness of
      IPV remains insufficient. CONCLUSIONS: IPV can be considered as a technique that
      may offer valuable assistance in the treatment of severe respiratory diseases
      that are refractory to conventional techniques of respiratory therapy.

PMID- 22405113
TI  - [Inhalation devices: characteristics, modeling, regulation and use in routine
      practice. GAT Aerosolstorming, Paris 2011].
AB  - Aerosoltherapy is a first-line treatment for chronic obstructive respiratory
      diseases such as asthma and COPD. Treatment modalities and devices are varied and
      the choice of the device must be adapted to and optimized for every patient.
      Spacers can be used for some categories of patients for whom the use of other
      devices turns out to be complicated. The improvement of these treatments requires
      the optimization of the lung deposition of inhaled particles; lung modeling plays
      an essential role in the understanding of the mechanisms of flow in the airways.
      Regulations must frame prescription of inhaled treatments to optimize its quality
      and, thus, the care for these chronic diseases. Many generally-accepted ideas
      concerning these treatments turn out to be false. Inhaled treatments are
      constantly evolving, both pharmacologically and technologically.

PMID- 22405114
TI  - [What tools should be used for follow-up post occupational exposure? What should
      be the frequency?].
AB  - As long as the value of screening for cancers related to asbestos is not proven
      in the population at risk, the medical benefits of follow-up post-professional
      exposure remain uncertain and the only justification is to answer the questions
      of anxious retired workers concerning the consequences of their past-exposure and
      to provide compensation for any abnormalities that are demonstrated. In this
      country, to answer the questions posed in the title of this contribution in the
      case of pathologies related to asbestos, it is necessary, after verifying the
      fact and the level of exposure, to identify the pleural or pulmonary fibrosis
      and, above all, the pleural plaques, which constitute the essential lesions
      currently screened for. Thoracic CT scanning without contrast is the examination
      of choice to achieve this objective. There are, however, two significant
      problems. On one hand there is a high incidence of pulmonary micronodules, the
      necessary surveillance of which requires subsequent scans, leading to increased
      irradiation and anxiety. On the other hand the diagnostic uncertainty concerning
      discrete lesions is a source of confusion for the persons followed-up. There are,
      at present, neither scientific criteria to determine the optimum frequency of
      examination nor any arguments for replacing the pragmatic proposals of the
      consensus conference of 1999. It is important, therefore, to provide a medical
      assessment appropriate to the symptoms and anxiety expressed by a person
      previously exposed to asbestos. Overall it is necessary to question the benefit
      to the exposed person, in terms of quality of life, of a regular search for
      lesions that would usually be asymptomatic if not identified. Would it not be
      more judicious and more equitable to compensate persons whose past-exposure is
      sufficient to increase significantly their risk of cancer independently of the
      presence of benign abnormalities.

PMID- 22405115
TI  - [COPD and erythropoiesis: interactions and consequences].
AB  - Erythropoiesis is modified in chronic obstructive pulmonary disease (COPD).
      Tobacco smoke, hypoxaemia, systemic inflammation, and infectious exacerbations
      are the main factors involved. Polymorphisms in genes involved in the regulation
      of erythropoiesis probably explain the individual susceptibility and variability
      in the response. The roles of comorbidities related to COPD and the impact of
      treatment on erythropoiesis are important confounding factors. While
      polycythaemia is often related to tobacco smoke and hypoxaemia, it has become
      less common due to the improvement of COPD follow-up and especially the
      initiation of long-term oxygen therapy. The control of the main causes is often
      sufficient, but in cases of severe polycythaemia an erythrapheresis is indicated.
      Anaemia has recently been reported as a more common and serious complication. It
      increases dyspnoea and reduces physical activity and quality of life. Its impact
      on survival and the requirements for healthcare has recently been confirmed. The
      main approach to the management of anaemia remains exclusion of any curable
      causes, reducing exacerbations and systemic inflammation, and controlling the
      comorbidities. Though erythropoietin has some benefits in the so-called "anaemia
      of chronic disease", this still remains to be confirmed in patients with COPD.

PMID- 22405116
TI  - [Asthma exacerbations: pharmacological prevention].
AB  - Asthma exacerbations are responsible for many emergency medical interventions and
      account for a significant proportion of the health costs of the disease.
      Increased airway inflammation is a key feature of exacerbations in asthma and
      therefore inhaled corticosteroids (ICS) are considered as first-line therapy for
      long-term asthma control. ICS have been demonstrated to reduce the risk of asthma
      exacerbations, as well as improving lung function. Oral leukotriene receptor
      antagonists also reduce the incidence of asthma exacerbations but are less
      effective than ICS. In patients with inadequately controlled persistent asthma
      despite low-dose ICS, the addition of a long-acting inhaled beta-agonist (LABA)
      should be considered. LABA should not be given alone and should always be
      associated with ICS in asthma. The anti-immunoglobulin E antibody, omalizumab,
      reduces severe exacerbations and emergency visits in patients with severe
      allergic asthma. In clinical trials measurement of the inflammatory response in
      induced sputum could provide information concerning appropriate drug therapy.
      Asthma-associated comorbidities should be investigated and treated, particularly
      in severe asthma. Despite a high prevalence of both gastro-oesophageal reflux and
      allergic rhinitis among patients with asthma, treatment with proton-pump
      inhibitors or nasal corticosteroids does not reduce the rate of asthma
      exacerbations.

PMID- 22405117
TI  - [Asthma: treatment of exacerbations].
AB  - INTRODUCTION: Exacerbations remain, in both adults and children, a common reason
      for emergency consultation. The management of the asthmatic patient with an acute
      exacerbation is well defined. BACKGROUND: The initial evaluation, based on the
      background risk factors and the clinical examination, will determine the choice
      of treatment and management. Treatment is based on bronchodilators and
      corticosteroids in the majority of cases. VIEWPOINTS: An episode of exacerbation
      may be the opportunity to establish contact with the patient (an educational
      approach) to improve the adherence to long-term treatment with inhaled
      corticosteroids, which remain the best way of preventing future exacerbations.
      CONCLUSION: Early and appropriate management of exacerbations of asthma should
      reduce asthma morbidity and mortality. It could also reduce the socioeconomic
      costs of these episodes and the number and duration of hospital admissions.

PMID- 22405118
TI  - [Epidemiology and risk factors of venous thromboembolism].
AB  - INTRODUCTION: Venous thromboembolism (VTE) is a common disease. The incidence
      rises markedly with increasing age; over the age of 75, the annual incidence
      reaches 1 per 100. BACKGROUND: Besides major risk factors (surgery, trauma and
      acute medical illness), four risk factors have to be taken into account in the
      management of VTE: increasing age, cancer, previous history of VTE and pregnancy.
      To date, with the exception of the antiphospholipid syndrome and antithrombin
      deficiency, "thrombophilias" do not appear to change the management of VTE.
      VIEWPOINTS: "Thrombophilias" are useful tools for understanding the
      pathophysiology of VTE. Therefore, further studies are needed to identify new
      biological anomalies and their impact on the risk of VTE. Recently, links between
      VTE and atherosclerosis have been demonstrated, leading to new concept of pan
      vascular disease and prevention. CONCLUSIONS: VTE is a major public health
      problem. The knowledge of VTE risk factors is of major importance in identifying
      high-risk patients and in reducing the incidence and mortality of VTE.

PMID- 22405119
TI  - [Tuberculosis in France in 2010: epidemiology, clinical presentation and
      microbiology].
AB  - INTRODUCTION: This article presents recent data and trends on the epidemiology,
      clinical presentation and microbiology of tuberculosis in France during 2010.
      STATE OF ART: In 2009, a total of 5759 cases were notified in France,
      representing a rate of 8.2 cases per 100,000. The notification rate was below 10
      per 100,000 in all French regions, except in Ile-de-France and French Guyana.
      Notification rates were higher in some population groups such as people born
      abroad, especially those born in Sub-Saharan Africa, and those recently arrived
      in France, as well as in homeless people. Pulmonary tuberculosis accounted for
      72% of notified cases, 49% of which were contagious (positive direct examination
      of sputum, positive culture). PERSPECTIVES-CONCLUSIONS: Except in 2007 and 2008
      the incidence of tuberculosis (TB) has fallen consistently in France for the last
      20 years and this was again the case in 2009. These results support the
      maintenance of a vigilant approach to the control of the disease and call for the
      enhancement of public health activities in population groups at higher risk of
      the disease.

PMID- 22405120
TI  - [Diagnosis of latent tuberculous infections (healthy, currently or potentially
      immunocompromised subjects)].
AB  - Latent tuberculosis infection is a pathophysiological and clinical entity. The
      diagnosis is based on immunological tests such as the tuberculin skin test or
      interferon-gamma release assays. Interpretation of the results depends on the
      clinical context. Their predictive value for the occurrence of tuberculous
      disease is low, except in the case of young children and immunocompromised
      patients. Guidelines for the diagnosis of latent tuberculous infection in
      different countries are reviewed. The development of more predictive tests is
      desirable.

PMID- 22405121
TI  - [Functional measurements of the peripheral airways in COPD].
AB  - INTRODUCTION: COPD is characterized by airflow limitation that is not fully
      reversible. Changes in the structure and function of the small airways (less than
      2mm diameter) are now recognized to play a major pathophysiological and
      mechanical role in airflow limitation in COPD. There is, therefore, a need for
      technology to quantify small airways disease. BACKGROUND: For the diagnosis and
      assessment of COPD, spirometry is the gold standard (postbronchodilator
      FEV(1)/FVC less than 70%). The ATS/ERS definition of an obstructive pulmonary
      defect contrasts with the definitions suggested by clinical guidelines, in that
      FEV(1) is related to VC rather than FVC and the cut-off value of this ratio is
      set at the 5(th) percentile of the normal distribution rather than at a fixed
      value of 0.7. There is also a significant association between the severity of the
      disease and the degree of inflammation in the small airways. Therefore, a variety
      of physiological tests have been proposed as non-invasive surrogate measurements
      of distal lung function, such as a reduction in the forced expiratory flow at 25%
      to 75% of forced vital capacity (FEF(25-75)). However, the reproducibility and
      comparability of the FEF(25-75) is limited if not adjusted for lung volume, and
      the relationship between FEF(25-75) and histology is unknown. It is difficult to
      quantify the narrowing of the small airways and physiological measurements are
      difficult to interpret because there is abnormal airflow in the larger airways.
      Therefore, it will be difficult to assess the effects of new treatments on small
      airway function, and it is important to develop new techniques in order to do so.
      VIEWPOINT: The single breath nitrogen washout, with calculation of the slope
      (dN(2)) of the N(2) alveolar plateau, the closing volume and the closing
      capacity, is a more sensitive test of early lung damage in smokers than the
      FEV(1). The Forced Oscillation Technique (FOT) is a method for assessing
      respiratory mechanics non-invasively during spontaneous breathing. The more
      sophisticated multiple breath washout test (MBW) has the potential to locate the
      affected small airways anatomically in acinar and conductive lung zones through
      increased phase III slope indices, Sacin and Scond. In more advanced stages of
      smoking-induced lung disease, differential patterns of Sacin and Scond are
      characteristics of parenchymal destruction in addition to peripheral airways
      changes. CONCLUSION: These functional tests are promising solutions for small
      airways assessment. FOT has the advantage of being a simple method, requiring
      only the passive cooperation of the subject.

PMID- 22405122
TI  - [Congenital lung malformations--when to operate?].
AB  - Advances in antenatal imaging over the past 10 years have completely changed
      diagnosis and management of congenital lung disease, especially for congenital
      cystic adenomatoid malformations and sequestrations that are the two lesions most
      commonly detected. If early surgical excision is required for symptomatic cases,
      management of asymptomatic malformations is still discussed. The natural
      evolution and consequences of later complications of congenital lung
      malformations need to be compared with the benefits of elective resection and
      surgical morbidity. Complete regression of sequestrations or clinical and
      morphological improvement in congenital lobar emphysema pleads for clinical
      watching. On the other hand, resection is advocated for cystic malformations,
      because of an increased risk of acute respiratory distress, later infections and
      the possibility of malignant transformation. Even though the proportion of
      asymptomatic patients that go on to develop symptoms is hard to evaluate, an
      argument for elective surgery is a better outcome than emergency surgery. Further
      studies and long term follow-up are still needed to understand the natural
      history of congenital lung malformations precisely and help to define the optimal
      way in which to manage them.

PMID- 22405123
TI  - [Congenital diaphragmatic hernia: respiratory and vascular outcomes].
AB  - Congenital diaphragmatic hernia (CDH) is a life-threatening anomaly associated
      with a variable degree of pulmonary hypoplasia (PH) and persistent pulmonary
      hypertension (PPH). Despite remarkable advances in neonatal resuscitation and
      intensive care, and new postnatal treatment strategies, the rates of mortality
      and morbidity in the newborn with CDH remain high as the result of severe
      respiratory failure secondary to PH and PPH. Later, lung function assessments
      show obstructive and restrictive impairments due to altered lung structure and
      lung damage due to prolonged ventilatory support. The long-term consequences of
      pulmonary hypertension are unknown. Other problems include chronic pulmonary
      aspiration caused by gastro-oesophageal reflux and respiratory manifestations of
      allergy such as asthma or rhinitis. Finally, failure to thrive may be caused by
      increased caloric requirements due to pulmonary morbidity. Follow-up studies that
      systematically assess long-term sequelae are needed. Based on such studies, a
      more focused approach for routine multidisciplinary follow-up programs could be
      established. It is the goal of the French Collaborative Network to promote
      exchange of knowledge, future research and development of treatment protocols.

PMID- 22405124
TI  - [Intrapulmonary percussion ventilation: operation and settings].
AB  - Intrapulmonary Percussion Ventilation (IPV) was designed to promote airway
      clearance, to recruit areas of lung and to improve pulmonary gas exchange. Its
      principle is to administer bursts of small tidal volume at high frequency. This
      article describes IPV devices, especially the Phasitron((r)), which provides a
      dynamic interface between the pneumatic source of gas and the patient. Although
      not fully understood, the principles of action are also discussed. Finally,
      available settings of IPV are proposed following two strategies. In patients with
      obstructive respiratory disease and ventilatory autonomy, the vibrations and
      percussions are applied with a frequency more than 300 cycles/min and pressure in
      the proximal airways ranging from 10-20cm. H(2)O. In patients with restrictive
      pulmonary disease but without ventilatory autonomy, IPV is expected to improve
      gas exchange. The frequency of percussion will be slower (80-200 cycles/min) but
      the proximal airway pressure may reach 40cm H(2)O. During the sessions, the
      frequency may be modified to alternate from a percussive pattern (high
      frequencies promoting the mobilization of secretions) to a ventilatory pattern
      (slow frequencies encouraging alveolar ventilation and clearance of secretions).

PMID- 22405126
TI  - Reading performance with different contrast characters in patients with central
      serous chorioretinopathy.

PMID- 22405125
TI  - Investigating cellular identity and manipulating cell fate using induced
      pluripotent stem cells.
AB  - Induced pluripotent stem (iPS) cells, obtained from reprogramming somatic cells
      by ectopic expression of a defined set of transcription factors or chemicals, are
      expected to be used as differentiated cells for drug screening or evaluations of
      drug toxicity and cell replacement therapies. As pluripotent stem cells, iPS
      cells are similar to embryonic stem (ES) cells in morphology and marker
      expression. Several types of iPS cells have been generated using combinations of
      reprogramming molecules and/or small chemical compounds from different types of
      tissues. A comprehensive approach, such as global gene or microRNA expression
      analysis and whole genomic DNA methylation profiling, has demonstrated that iPS
      cells are similar to their embryonic counterparts. Considering the substantial
      variation among iPS cell lines reported to date, the safety and therapeutic
      implications of these differences should be thoroughly evaluated before they are
      used in cell therapies. Here, we review recent research defining the concept of
      standardization for iPS cells, their ability to differentiate and the identity of
      the differentiated cells.

PMID- 22405127
TI  - Reasons for and against participation in studies of medicinal therapies for women
      with breast cancer: a debate.
AB  - BACKGROUND: A special challenge for research studies of breast cancer among
      females is low patient participation rates. We compiled this systematic review to
      identify reasons why women with, or at high risk of, breast cancer do or do not
      participate in medicinal studies of breast cancer. METHOD: A systematic
      literature search in the databases Cochrane Library, EMBASE, Medline, Pascal
      Biomed, ACP Journal Club and CINAHL, as well as searches through reference lists
      of relevant texts, was performed. RESULTS: Of 39 relevant full texts, ultimately,
      nine studies (1 qualitative, 8 quantitative) were included after applying the
      inclusion criteria. Despite a lack of data material, it was possible to identify
      various factors influencing women's willingness to participate in medicinal
      studies and group them into three categories: person-related, study-related, and
      physician-related. CONCLUSION: Reasons for or against participation in studies of
      medicinal therapies by women with, or at high risk of, breast cancer are multi
      dimensional, and should be considered when planning such studies to garner higher
      participation rates. For a more comprehensive picture of factors that affect
      participation, further studies in this field are recommended.

PMID- 22405128
TI  - Magnetic enhancement of cell retention, engraftment, and functional benefit after
      intracoronary delivery of cardiac-derived stem cells in a rat model of
      ischemia/reperfusion.
AB  - The efficiency of stem cell transplantation is limited by low cell retention.
      Intracoronary (IC) delivery is convenient and widely used but exhibits
      particularly low cell retention rates. We sought to improve IC cell retention by
      magnetic targeting. Rat cardiosphere-derived cells labeled with iron microspheres
      were injected into the left ventricular cavity of syngeneic rats during brief
      aortic clamping. Placement of a 1.3 Tesla magnet ~1 cm above the heart during and
      after cell injection enhanced cell retention at 24 h by 5.2-6.4-fold when 1, 3,
      or 5 * 10(5) cells were infused, without elevation of serum troponin I (sTnI)
      levels. Higher cell doses (1 or 2 * 10(6) cells) did raise sTnI levels, due to
      microvascular obstruction; in this range, magnetic enhancement did not improve
      cell retention. To assess efficacy, 5 * 10(5) iron-labeled, GFP-expressing cells
      were infused into rat hearts after 45 min ischemia/20 min reperfusion of the left
      anterior coronary artery, with and without a superimposed magnet. By quantitative
      PCR and optical imaging, magnetic targeting increased cardiac retention of
      transplanted cells at 24 h, and decreased migration into the lungs. The enhanced
      cell engraftment persisted for at least 3 weeks, at which time left ventricular
      remodeling was attenuated, and therapeutic benefit (ejection fraction) was
      higher, in the magnetic targeting group. Histology revealed more GFP(+)
      cardiomyocytes, Ki67(+) cardiomyocytes and GFP(-)/ckit(+) cells, and fewer
      TUNEL(+) cells, in hearts from the magnetic targeting group. In a rat model of
      ischemia/reperfusion injury, magnetically enhanced intracoronary cell delivery is
      safe and improves cell therapy outcomes.

PMID- 22405129
TI  - The effects of yohimbine on the pharmacokinetic parameters of detomidine in the
      horse.
AB  - OBJECTIVE: To describe the pharmacokinetics of detomidine and yohimbine when
      administered in combination. STUDY DESIGN: Randomized crossover design. ANIMALS:
      Nine healthy adult horses aged 9 +/- 4 years and weighing of 561 +/- 56 kg.
      METHODS: Three dose regimens were employed in the current study. 1) 0.03 mg kg(
      1) detomidine IV (D), 2) 0.2 mg kg(-1) yohimbine IV (Y) and 3) 0.03 mg kg(-1)
      detomidine IV followed 15 minutes later by 0.2 mg kg(-1) yohimbine IV (DY). Each
      horse received all three dose regimens with a minimum of 1 week in between
      subsequent regimens. Blood samples were obtained and plasma analyzed for
      detomidine and yohimbine concentrations by liquid chromatography-mass
      spectrometry. Data were analyzed using both non-compartmental and compartmental
      analysis. RESULTS: The maximum measured detomidine concentrations were 76.0 and
      129.9 ng mL(-1) for the D and DY treatments, respectively. Systemic clearance and
      volume of distribution of detomidine were not significantly different for either
      treatment. There was a significant increase in the maximum measured yohimbine
      plasma concentrations from Y (173.9 ng mL(-1)) to DY (289.8 ng mL(-1)). Both the
      Cl and V(d) for yohimbine were significantly less (6.8 mL minute(-1) kg(-1) (Cl)
      and 1.7 L kg(-1) (V(d) )) for the DY as compared to the Y treatments (13.9 mL
      minute(-1) kg(-1) (Cl) and 2.7 L kg(-1) (V(d))). Plasma concentrations were below
      the limit of quantitation (0.05 and 0.5 ng mL(-1)) by 18 hours for both
      detomidine and yohimbine. CONCLUSION AND CLINICAL RELEVANCE: The Cl and V(d) of
      yohimbine were affected by prior administration of detomidine. The elimination
      half life of yohimbine remained unaffected when administered subsequent to
      detomidine. However, the increased plasma concentrations in the presence of
      detomidine has the potential to cause untoward effects and therefore further
      studies to assess the physiologic effects of this combination of drugs are
      warranted.

PMID- 22405130
TI  - Binding of Lassa virus perturbs extracellular matrix-induced signal transduction
      via dystroglycan.
AB  - The arenavirus Lassa virus (LASV) causes a severe haemorrhagic fever with high
      mortality in man. The cellular receptor for LASV is dystroglycan (DG). DG is a
      ubiquitous receptor for extracellular matrix (ECM) proteins, which cooperates
      with beta1 integrins to control cell-matrix interactions. Here, we investigated
      whether LASV binding to DG triggers signal transduction, mimicking the natural
      ligands. Engagement of DG by LASV resulted in the recruitment of the adaptor
      protein Grb2 and the protein kinase MEK1 by the cytoplasmic domain of DG without
      activating the MEK/ERK pathway, indicating assembly of an inactive signalling
      complex. LASV binding to cells however affected the activation of the MEK/ERK
      pathway via alpha6beta1 integrins. The virus-induced perturbation of alpha6beta1
      integrin signalling critically depended on high-affinity LASV binding to DG and
      DG's cytoplasmic domain, indicating that LASV-receptor binding perturbed
      signalling cross-talk between DG and beta1 integrins.

PMID- 22405131
TI  - Aromatase inhibitors, estrogens and musculoskeletal pain: estrogen-dependent T
      cell leukemia 1A (TCL1A) gene-mediated regulation of cytokine expression.
AB  - INTRODUCTION: Arthralgias and myalgias are major side effects associated with
      aromatase inhibitor (AI) therapy of breast cancer. In a recent genome-wide
      association study, we identified SNPs - including one that created an estrogen
      response element near the 3' end of the T-cell leukemia 1A (TCL1A) gene - that
      were associated with musculoskeletal pain in women on adjuvant AI therapy for
      breast cancer. We also showed estrogen-dependent, SNP-modulated variation in
      TCL1A expression and, in preliminary experiments, showed that TCL1A could induce
      IL-17RA expression. In the present study, we set out to determine whether these
      SNPs might influence cytokine expression and effect more widely, and, if so, to
      explore the mechanism of TCL1A-related AI-induced side effects. METHODS: The
      functional genomic experiments performed included determinations of TCL1A,
      cytokine and cytokine receptor expression in response to estrogen treatment of
      U2OS cells and lymphoblastoid cell lines that had been stably transfected with
      estrogen receptor alpha. Changes in mRNA and protein expression after gene
      knockdown and overexpression were also determined, as was NF-kappaB
      transcriptional activity. RESULTS: Estradiol (E2) increased TCL1A expression and,
      in a TCL1A SNP-dependent fashion, also altered the expression of IL-17, IL-17RA,
      IL-12, IL-12RB2 and IL-1R2. TCL1A expression was higher in E2-treated
      lymphoblastoid cell lines with variant SNP genotypes, and induction of the
      expression of cytokine and cytokine receptor genes was mediated by TCL1A.
      Finally, estrogen receptor alpha blockade with ICI-182,780 in the presence of E2
      resulted in greatly increased NF-kappaB transcriptional activity, but only in
      cells that carried variant SNP genotypes. These results linked variant TCL1A SNP
      sequences that are associated with AI-dependent musculoskeletal pain with
      increased E2-dependent TCL1A expression and with downstream alterations in
      cytokine and cytokine receptor expression as well as NF-kappaB transcriptional
      activity. CONCLUSIONS: SNPs near the 3' terminus of TCL1A were associated with AI
      dependent musculoskeletal pain. E2 induced SNP-dependent TCL1A expression, which
      in turn altered IL-17, IL-17RA, IL-12, IL-12RB2, and IL-1R2 expression as well as
      NF-kappaB transcriptional activity. These results provide a pharmacogenomic
      explanation for a clinically important adverse drug reaction as well as insights
      into a novel estrogen-dependent mechanism for the modulation of cytokine and
      cytokine receptor expression.

PMID- 22405132
TI  - Achieving international consensus for the prevention of orthopaedic wound
      blistering: results of a Delphi survey.
AB  - This article presents the results of an international 2 stage Delphi survey
      carried out via e-mail to achieve consensus as to the most effective
      postoperative wound management to prevent blistering and other complications.
      Seventeen prospective participants were invited to be members of the Delphi Panel
      of which 13 agreed to be involved. The panel suggested that an ideal wound
      dressing would conform easily to the wound, be easy to apply and remove, allow
      for swelling and minimise pain on removal. Participants were in agreement that
      the primary wound dressing should be left in situ for as long as possible,
      providing there was no excessive oozing or signs of infection. The authors
      recognise that the Delphi Panel was relatively compact; however, the study
      arguably provides some useful data that can be used to identify the consequences
      of wound blistering and important factors that need to be considered when
      choosing a wound dressing to prevent blistering.

PMID- 22405134
TI  - Current applications of optical coherence tomography for coronary intervention.
AB  - Optical coherence tomography (OCT) is the 'new kid on the block' in coronary
      imaging. This technology offers clinicians a high resolution (approximately 15
      MUm), that is ten times higher than the currently accepted gold standard of
      intravascular ultrasound and has emerged as the ideal imaging tool for the
      assessment of superficial components of coronary plaques and stent struts. Novel
      OCT systems can perform quick and safe scanning of coronary arteries with a non
      occlusive technique. A brief summary containing the key physical principles of
      OCT technology with particular attention to the novel Fourier domain system is
      presented. This review will focus on clinical and research applications of OCT in
      interventional cardiology. The two main fields of OCT in vivo: coronary
      atherosclerosis assessment and the study of vessel wall response to stent
      implantation in terms of strut coverage and apposition will be delineated.
      Limitations and future perspectives of the technique are presented.

PMID- 22405135
TI  - Right atrium vegetation in prosthetic aortic endocarditis.

PMID- 22405133
TI  - What does the concept of the stem cell niche really mean today?

PMID- 22405136
TI  - Pneumococcal polyarticular septic arthritis after a single infusion of infliximab
      in a rheumatoid arthritis patient: a case report.
AB  - INTRODUCTION: We present a case of Streptococcus pneumoniae polyarticular septic
      arthritis in a patient with rheumatoid arthritis receiving a single infusion of
      infliximab. CASE PRESENTATION: A 38-year-old Japanese man with a 5-year history
      of seronegative rheumatoid arthritis had previously received sulphasalazine and
      methotrexate therapies and was on regular low-dose prednisolone therapy. Despite
      these treatments, his disease activity remained high and infliximab was
      introduced in addition to methotrexate, prednisolone, and folic acid. However, he
      was admitted to hospital with a fever of 40.6 degrees C, chills, and
      polyarthralgia eight days after the first infusion of infliximab. His joints were
      swollen, painful, and warm. Laboratory data showed marked acute inflammation. He
      was diagnosed with bacterial septic polyarthritis, and emergency surgical joint
      lavage and drainage was performed at the knees along with needle aspiration and
      lavage of the ankles and right wrist. He was then given intravenous antibiotic
      therapy for 31 days. He made a good recovery and was discharged on day 37.
      CONCLUSIONS: We believe this is the first reported case of severe pneumococcal
      septic arthritis requiring hospitalization in a patient treated with infliximab.
      S. pneumonia is now a well-recognized but uncommon cause of polyarticular septic
      arthritis that can lead to cessation of therapy, as in our patient's case.

PMID- 22405137
TI  - Introduction to methods in invertebrate muscle biology.

PMID- 22405138
TI  - [Is it necessary to identify the isolates of the Streptococcus bovis group
      correctly at subspecies level?].

PMID- 22405139
TI  - [Molecular diagnosis of human papillomavirus: new challenges in a different
      scenario].

PMID- 22405140
TI  - [Visceral leishmaniasis diagnosed from a colon biopsy].

PMID- 22405141
TI  - [Is preseptal cellulitis of the eyelid always a trivial disease?].

PMID- 22405142
TI  - Insights into the uptake mechanism of NrTP, a cell-penetrating peptide
      preferentially targeting the nucleolus of tumour cells.
AB  - Nucleolar targeting peptides are 14-15 residue-long sequences designed by
      structural minimization of a snake toxin (J Med Chem 2008;50:7041). Peptides such
      as NrTP1 (YKQCHKKGGKK GSG) and analogues are capable of penetrating human cervix
      epithelial carcinoma cells and homing into their nucleoli. We now show that NrTP1
      similarly penetrates and localizes in the nucleolus of tumour cells derived from
      human pancreatic (BxPC-3) and human ductal mammary gland (BT-474) carcinomas.
      Live cell confocal microscopy imaging, combined with flow cytometry analysis of
      cells arrested to defined phases of their cycle, confirms that NrTP1 uptake and
      nucleolar homing are independent of cell cycle phase. Peptide uptake is
      significantly reduced at low temperature. Also, drugs inhibiting chlatrin
      mediated endocytosis severely decrease uptake, pointing to a clathrin-dependent
      route as the primary NrTP1 internalization mechanism. These results highlight
      nucleolar targeting peptides not only as a novel and efficient class of cell
      penetrating peptides but also for their exceptional ability to target
      preferentially an essential and dynamic subnuclear structure such as the
      nucleolus.

PMID- 22405143
TI  - Effect of environment and fallow period on Cosmopolites sordidus population
      dynamics at the landscape scale.
AB  - Understanding how the population dynamics of insect pests are affected by
      environmental factors and agricultural practices is important for pest
      management. To investigate how the abundance of the banana weevil, Cosmopolites
      sordidus (Coleoptera: Curculionidae), is related to environmental factors and the
      length of the fallow period in Martinique, we developed an extensive data set
      (18,130 observations of weevil abundance obtained with pheromone traps plus
      associated environmental data) and analysed it with generalized mixed-effects
      models. At the island scale, C. sordidus abundance was positively related to mean
      temperature and negatively related to mean rainfall but was not related to soil
      type. The number of insects trapped was highest during the driest months of the
      year. Abundance of C. sordidus decreased as the duration of the preceding fallow
      period increased. The latter finding is inconsistent with the view that fallow
      generated decomposing banana tissue is an important resource for larvae that
      leads to an increase in the pest population. The results are consistent with the
      view that fallows, in association with pheromone traps, are effective for the
      control of the banana weevil. 

PMID- 22405146
TI  - Associations between sexual and reproductive health communication and health
      service use among U.S. adolescent women.
AB  - CONTEXT: An understanding of the association between adolescents' sexual and
      reproductive health knowledge and their use of relevant services is needed to
      improve young people's sexual and reproductive health. METHODS: Data from the
      National Survey of Family Growth were used to examine associations between sexual
      and reproductive health communication (parental and formal) and service use among
      2,326 U.S. women aged 15-19 in 2002 and 2006-2008. Chi-square tests and
      multivariate logistic regression were used to assess relationships between
      adolescents' receipt of sexual and reproductive health communication from parents
      and formal (school, church, community) sources and their use of sexual and
      reproductive health services. RESULTS: The majority of adolescents had received
      parental (75%) and formal (92%) sexual and reproductive health communication; 43%
      reported recent service use. In unadjusted analyses, parental and formal
      communication were positively associated with service use. In regression models,
      overall parental communication remained positively associated with service use
      (odds ratio, 1.6); parental abstinence-only communication, which was not
      significant in 2002, was associated with reduced odds of service use for the
      pooled sample (0.4) and in 2006-2008 (0.3). Formal communication was not
      associated with service use. CONCLUSIONS: Further research is needed to assess
      whether comprehensive sexual and reproductive health communication facilitates
      adolescents' health care utilization. Examination of how communication sources,
      quality and content are related to service use is needed to understand
      adolescents' sexual and reproductive health knowledge and needs.

PMID- 22405147
TI  - Prenatal care and subsequent birth intervals.
AB  - CONTEXT: Prenatal care generally includes contraceptive and health education that
      may help women to control their subsequent fertility. However, research has not
      examined whether receipt of prenatal care is associated with subsequent
      birthspacing. METHODS: Longitudinally linked birth records from 113,662 New
      Jersey women who had had a first birth in 1996-2000 were used to examine
      associations between the timing and adequacy of prenatal care prior to a woman's
      first birth and the timing of her second birth. Multinomial logistic regression
      analyses adjusted for social and demographic characteristics, hospital and year
      of birth. RESULTS: Most women (85%) had initiated prenatal care during the first
      trimester. Women who had not obtained prenatal care until the second or third
      trimester, or at all, were more likely than those who had had first-trimester
      care to have a second child within 18 months, rather than in 18-59 months (odds
      ratios, 1.2-1.6). Similarly, women whose care had been inadequate were more
      likely than those who had had adequate care to have a short subsequent birth
      interval (1.2). The associations were robust to alternative measures of prenatal
      care and birth intervals, and were strongest for mothers with less than 16 years
      of education. CONCLUSIONS: Providers should capitalize on their limited
      encounters with mothers who initiate prenatal care late or use it sporadically to
      ensure that these women receive information about family planning.

PMID- 22405148
TI  - Use of levonorgestrel emergency contraception in Utah: is it more than "plan B"?
AB  - CONTEXT: It is important to understand why some women use levonorgestrel
      emergency contraceptive pills repeatedly, because the method is not intended for
      repeated use, and current evidence suggests that it is approximately 77%
      effective at preventing pregnancy. METHODS: An anonymous patient survey of 1,040
      women aged 18-29 purchasing levonorgestrel at Planned Parenthood clinics in Utah
      was conducted during a 4-6-week period in 2007. Chi-square tests and analyses of
      variance were used to examine associations between selected characteristics and
      level of levonorgestrel use. Logistic regression was used to assess
      characteristics independently associated with repeated use. RESULTS: Twenty-nine
      percent of participants had used levonorgestrel more than twice in the prior
      year. Fifty-eight percent believed that levonorgestrel is at least 90% effective
      in protecting against pregnancy; 16% believed that it is 100% effective. In
      univariate analyses, lifetime number of partners, currently having multiple
      partners, substance use at last intercourse and perceived effectiveness of
      levonorgestrel were positively associated with repeated levonorgestrel use in the
      previous year. The measure most strongly associated with repeated levonorgestrel
      use in multivariate analyses was perceived effectiveness: Women who believed that
      the method is 90-99% or 100% effective in preventing pregnancy had greater odds
      of repeated use than those who believed it is 75-89% effective (odds ratios, 1.8
      each). CONCLUSION: Women who repeatedly use levonorgestrel may have an inflated
      perception of its effectiveness. Future research, including qualitative research,
      may help clarify factors that lead to inflated perceptions of effectiveness.

PMID- 22405149
TI  - Missed conceptions or misconceptions: perceived infertility among unmarried young
      adults in the United States.
AB  - CONTEXT: Perceived infertility is an individual's belief that she or he is unable
      to conceive or impregnate, regardless of whether this belief is medically
      accurate. This perception may lead to contraceptive nonuse, which may, in turn,
      lead to unintended pregnancy. Little research has examined perceived infertility
      among young adults, including potential associations with contraceptive
      behaviors. METHODS: The frequency of perceived infertility among young adults was
      assessed using 2009 data from a nationally representative telephone survey of
      1,800 unmarried men and women aged 18-29. Multinomial regression analyses
      assessed associations between respondents' perceived infertility and selected
      background, reproductive knowledge, sexual experience and contraceptive use
      characteristics. RESULTS: Overall, 19% of women and 13% of men believed that they
      were very likely to be infertile. Hispanic women and women who had received
      public assistance in the past year had elevated odds of perceived infertility
      (odds ratios, 3.4 and 3.0, respectively), as did Hispanic men and men of other
      racial or ethnic minorities, except blacks (2.5 and 6.1, respectively). Men who
      had some college education, had received sex education or were not in a current
      relationship had decreased odds of thinking they were very likely to be infertile
      (0.3-0.4). Among men, perceived infertility was associated with the belief that
      they were likely to have sex without using a contraceptive in the next three
      months (2.6). CONCLUSIONS: A substantial proportion of young adults believe they
      are infertile. Improved provider counseling and sex education may be useful in
      helping them to better understand their actual probability of infertility, and
      this knowledge may lead to improved contraceptive use.

PMID- 22405151
TI  - Designing messages to motivate parents to get their preteenage sons vaccinated
      against human papillomavirus.
AB  - CONTEXT: Human papillomavirus (HPV) vaccine, licensed for use in 9--26-year-olds,
      is most effective when given before sexual activity begins. HPV causes genital
      warts, is associated with several cancers and disproportionately affects racial
      and ethnic minorities. Parents are typically unaware of male HPV vaccine;
      messages that might motivate them to get their preteenage sons vaccinated are
      unexplored. METHODS: Messages promoting vaccination of preteenage boys were
      designed and tested in 2009 and 2010. Five focus groups were conducted with 29
      black parents of 11-12-year-old boys, recruited through three churches and a
      middle school in North Carolina, and a racially diverse sample of 100 parents of
      9-13-year-old boys in a university-based adolescent health clinic was
      interviewed. A constant comparison method was used to code transcripts and
      interpret themes. Chi-square and t tests or analyses of variance were used to
      assess differences in quantitative data. RESULTS: Focus group parents knew little
      about HPV in males. Although concerned about safety and cost, parents supported
      vaccination for their sons. They wanted to see racial diversity and both parents
      in motivational materials. In interviews, 89% of parents reported never having
      heard of male HPV vaccine. The largest proportion said that a message stressing
      the prevalence and possible consequences of HPV infection was the most motivating
      (32%); the design favored by the largest proportion (43%) showed two parents.
      CONCLUSIONS: Messages that may most motivate parents to get preteenage boys
      vaccinated against HPV focus on infection risk and include images of parents with
      their sons.

PMID- 22405152
TI  - Patterns of sexual partnering and reproductive history: associations with timing
      of first birth in a birth cohort.
AB  - CONTEXT: The associations between timing of first live birth and previous sexual
      behavior and pregnancies are not well understood. METHODS: Members of a 1972-1973
      New Zealand birth cohort were surveyed at ages 21, 26 and 32 about their sexual
      and reproductive histories; 506 men and 479 women participated in at least one
      assessment. Relative risks and 95% confidence intervals were calculated using
      Poisson regression to examine associations between the likelihood of first live
      birth at specific ages (prior to age 21, at age 21-25, at age 26-31) and selected
      characteristics. RESULTS: Birth prior to age 21 was more likely for men and women
      who initiated intercourse before age 15 (relative risks, 3.1 and 2.0,
      respectively), and less likely for those who initiated at age 18 or later (0.3
      and 0.1, respectively), than for those aged 15-17 at first coitus. Prior
      miscarriage was associated (although sometimes marginally) with an elevated
      likelihood of first birth across genders and ages (1.7-1.8). Prior abortion was
      associated with an elevated likelihood of first birth at age 21-25 for women
      (1.6) and a reduced likelihood at age 26-31 for men (0.5). Having multiple sexual
      partners at age 21-25 was negatively associated with the likelihood of a first
      birth at age 26-31 for men. Marriage and cohabitation were positively associated
      with birth timing. CONCLUSIONS: Early sexual initiation and relationship
      instability may promote parenthood at younger ages, whereas greater relationship
      stability may do so at older ages.

PMID- 22405153
TI  - Variation in state unintended pregnancy rates in the United States.
AB  - CONTEXT: Newly available data show large differences in rates of unintended
      pregnancy across states. Because key policy and program decisions that could
      affect these rates are made by state governments, it is important to assess
      whether characteristics of the states are associated with this variation.
      METHODS: Regression analysis was used to assess the relationship between the
      variation in state unintended pregnancy rates in 2006 and state-level aggregate
      measures of demographic composition, socioeconomic conditions, contraceptive use,
      and funding of and access to family planning services. RESULTS: State unintended
      pregnancy rates were positively associated with the proportion of resident women
      who were black or Hispanic. However, these associations were almost entirely
      accounted for by differences in the age and marital status of women, the
      proportion without health insurance and the proportion receiving Medicaid. In
      addition, these last two measures were strongly associated with state unintended
      pregnancy rates after the other measures were controlled for: An increase in the
      proportion of women uninsured was associated with elevated unintended pregnancy
      rates, and an increase in the proportion receiving Medicaid coverage was
      associated with reduced rates. CONCLUSIONS: State programs and policies should
      pay particular attention to increasing support for family planning services for
      minority groups. Findings also suggest that insurance coverage and receipt of
      Medicaid among women of reproductive age deserve further exploration as
      potentially important mechanisms for reducing state unintended pregnancy rates.

PMID- 22405160
TI  - Retinal vessel diameter can reliably be determined in minipigs using Retinal
      Vessel Analyser with a microscope-mounted fundus camera.
AB  - PURPOSE: Retinal Vessel Analyser (RVA) is a validated instrument to measure
      retinal vessel diameter in humans. The purpose of this study was to assess the
      reproducibility (inter-observer reliability) and the repeatability (test-retest
      reliability) of RVA with a microscope-mounted fundus camera to determine retinal
      vessel diameter in minipigs. METHODS: Ocular fundus image from five anaesthetized
      minipigs was recorded in a digital videotape for approximately 5 min, under
      stable systemic arterial pressure and gas conditions. To evaluate the
      reproducibility, each one of two investigators used RVA to measure the diameter
      of the superior temporal retinal artery on five separate 30-second video
      sequences from each minipig, which were the same video sequences for both
      investigators. To evaluate the repeatability, one investigator performed five
      measurements on a single, randomly selected, 30-second video sequence from each
      minipig. The reproducibility was determined using the intra-class correlation
      coefficient (ICC), and the repeatability was assessed using the coefficient of
      variation (COV). Bland-Altman plots were also used to assess agreement between
      the two investigators. RESULTS: Retinal arteriolar diameter measurements with RVA
      in minipigs were highly reproducible. Differences between the two investigators
      were lower than 0.7%. The ICC was 1.00, indicating perfect reproducibility, and
      the mean COV was 0.18%, reflecting excellent repeatability of the measurements
      with RVA. CONCLUSION: Retinal vessel diameter can reliably be determined not only
      in humans, but also in minipigs, using the commercially available RVA apparatus
      and a microscope-mounted fundus camera.

PMID- 22405161
TI  - Iron replacement therapy in inflammatory bowel disease patients with iron
      deficiency anemia: a systematic review and meta-analysis.
AB  - BACKGROUND AND AIMS: Iron deficiency anemia (IDA) is a common problem in patients
      with Inflammatory Bowel Disease (IBD) and has a significant negative impact on
      quality of life. The aim was to compare the clinical efficacy of intravenous (IV)
      versus oral (PO) iron replacement in adult IBD with iron deficiency anemia (IDA).
      METHODS: A systematic search for randomized controlled trials comparing the
      efficacy of IV versus PO iron therapy in the treatment of IDA in adult IBD
      patients. The primary outcome was the mean change in the hemoglobin at the end of
      study and secondary outcomes include mean change in ferritin, clinical disease
      activity index, quality of life score and the adverse reaction rate. RESULTS: The
      search strategy identified 757 articles while only three industry-funded articles
      met the inclusion criteria for systematic review and meta-analysis. The total
      sample size was 333 patients with 203 patients receiving IV therapy. IV route was
      associated with a 6.8 g/L higher mean hemoglobin increment and 110 MUg/L higher
      mean ferritin increment. The IBD activity index and Quality of Life scores were
      comparable between the two treatment groups. More adverse events were reported in
      the oral treatment group with the odds for discontinuation being 6.2 (CI 2.2,
      17.1). CONCLUSIONS: Intravenous iron treatment is better tolerated and more
      effective than oral iron treatment in improving ferritin. The higher hemoglobin
      gain with the IV route was small and of uncertain clinical significance. The
      combined sample size of the included studies was small and further clinical
      trials are required.

PMID- 22405162
TI  - Genital fistulas in female Crohn's disease patients.: clinical characteristics
      and response to therapy.
AB  - BACKGROUND: Genital fistulas (GF) can arise in the course of Crohn's disease
      (CD), are difficult to manage and determine a significant alteration of the
      quality of life. AIMS: To review the joint experience of the Inflammatory Bowel
      Disease Units in six University Hospitals in the management of GF in Crohn's
      disease on female patients. RESULTS: A total of 47 patients with GF were
      identified, affecting 3.8% of women with CD treated in our centers. A 47.5% of
      patients were smokers. The median of time from the diagnosis of CD reached 102
      months. According to anatomical type, GF were classified as rectovaginal (74.5%),
      anovaginal/anovulvar (21.3%) and enterovaginal (4.3%). Main symptoms were vaginal
      discharge of fecal material (55.3%), vaginal passage of gas (40.4%), or both.
      Fistulas were treated with antibiotics in 59.6% of patients, without any lasting
      success. Thiopurines were used in 80.9% of cases, with 13.2% of complete and
      23.7% of partial responses. Anti TNF-alpha therapy was applied in 63.8%, with a
      16.7% of complete and a 30% of partial responses (all responding patients
      received infliximab). Surgery was indicated in 38.3% of patients, with a 22% of
      complete responses after a first operation and 38.8% after reintervention. In
      all, definitive closure after one or more of these therapies was achieved in only
      31.9% of cases. CONCLUSION: Genital fistulas are a significant problem in female
      Crohn's disease patients. Therapy is not well defined and only partially
      effective (one in three cases). Surgical therapy stands out as the most effective
      treatment.

PMID- 22405163
TI  - Infliximab and complications after colectomy in patients with ulcerative colitis.
AB  - BACKGROUND: Infliximab treatment may increase the risk of subsequent
      postoperative complications in patients with ulcerative colitis. The main purpose
      of the present study therefore was to assess postoperative complications in
      patients who have undergone colectomy for ulcerative colitis with and without
      previous infliximab treatment. METHODS: Through a database search within a five
      year period ulcerative colitis patients in a single highly specialized
      department, who had undergone colectomy, were identified. In total 71 ulcerative
      colitis patients were identified and analyzed according to pretreatment with
      infliximab or not. Twenty patients who had received infliximab within 12 weeks
      prior to colectomy were compared to 51 patients on standard treatment. Data on
      patient background, concomitant medication, endoscopic and the laboratory
      results, clinical activity, and complications within 30 days after colectomy were
      recorded. RESULTS: At primary surgery, patient groups were similar with respect
      to distribution on gender, age, smoking behavior and concomitant medication.
      There were significant differences in partial Mayo-scores (7,95 (IFX) vs. 7,64,
      P=0.032); preoperative CRP-levels (42,72 (IFX) vs. 63,2, P=0.05); postoperative
      hospitalization time (10,9 (IFX) vs. 11,3 days, P=0.039); and in number of
      patients who underwent elective surgery (10% vs. 37,3%, P=0.015). There was no
      short-term mortality in either group and no significant difference in terms of
      postoperative complications between patients treated with IFX or not. However,
      the number of postoperative infectious complications was increased in
      corticosteroid-treated patients irrespective of IFX or not (45,8% in CS group vs.
      13,0%, P=0.028). CONCLUSIONS: The use of infliximab does not seem to associate
      with an increased risk of short-term postoperative complications in ulcerative
      colitis.

PMID- 22405164
TI  - Inter-observer agreement for Crohn's disease sub-phenotypes using the Montreal
      Classification: How good are we? A multi-centre Australasian study.
AB  - BACKGROUND: Crohn's disease (CD) exhibits significant clinical heterogeneity.
      Classification systems attempt to describe this; however, their utility and
      reliability depends on inter-observer agreement (IOA). We therefore sought to
      evaluate IOA using the Montreal Classification (MC). METHODS: De-identified
      clinical records of 35 CD patients from 6 Australian IBD centres were presented
      to 13 expert practitioners from 8 Australia and New Zealand Inflammatory Bowel
      Disease Consortium (ANZIBDC) centres. Practitioners classified the cases using MC
      and forwarded data for central blinded analysis. IOA on smoking and medications
      was also tested. Kappa statistics, with pre-specified outcomes of kappa>0.8
      excellent; 0.61-0.8 good; 0.41-0.6 moderate and <=0.4 poor, were used. RESULTS:
      97% of study cases had colonoscopy reports, however, only 31% had undergone a
      complete set of diagnostic investigations (colonoscopy, histology, SB imaging).
      At diagnosis, IOA was excellent for age, kappa=0.84; good for disease location,
      kappa=0.73; only moderate for upper GI disease (kappa=0.57) and disease
      behaviour, kappa=0.54; and good for the presence of perianal disease, kappa=0.6.
      At last follow-up, IOA was good for location, kappa=0.68; only moderate for upper
      GI disease (kappa=0.43) and disease behaviour, kappa=0.46; but excellent for the
      presence/absence of perianal disease, kappa=0.88. IOA for immunosuppressant use
      ever and presence of stricture were both good (kappa=0.79 and 0.64 respectively).
      CONCLUSION: IOA using MC is generally good; however some areas are less
      consistent than others. Omissions and inaccuracies reduce the value of clinical
      data when comparing cohorts across different centres, and may impair the ability
      to translate genetic discoveries into clinical practice.

PMID- 22405165
TI  - Magnetic resonance enteroclysis in patients with Crohn's disease: fat saturated
      T2-weighted sequences for evaluation of inflammatory activity.
AB  - BACKGROUND AND AIMS: To evaluate fat saturated (fs) T2-weighted (w) fast
      relaxation fast spin echo (FRFSE)-sequences compared to the standard protocol
      with contrast agent for the evaluation of inflammatory activity in patients with
      Crohn's Disease (CD). METHODS: Fourty-eight patients (male, 17; female, 33; mean
      age, 37 years) with suspicion of inflammatory activity in proven CD who underwent
      MR enteroclysis (MRE) at 1.5T (GE Healthcare) were retrospectively included. Two
      blinded radiologists analyzed MRE images for presence and extent of CD lesions
      and degree of local inflammation for fsT2-w FRFSE and contrast enhanced T1-w
      images (T2-activity; T1-activity; score, 1-4) in consensus. Furthermore, mural
      signal intensity (SI) ratios (T2-ratio; T1-ratio) were recorded. Patient based
      MRE findings were correlated with endoscopic (45 patients), surgical (6
      patients), histopathological, and clinical data (CDAI) as a surrogate reference
      standard. RESULTS: In total, 24 of 48 eligible patients presented with acute
      inflammatory activity with 123 affected bowel segments. ROC analysis of the total
      inflammatory score presented an AUC of 0.93 (p<0.001) for T2-activity (T1
      activity, AUC 0.63; p=0.019). ROC analysis revealed an AUC of 0.76 (p<0.001) for
      the T2-ratio (T1-ratio, AUC 0.51; p=0.93). General linear regression model
      revealed T2-activity (p=0.001) and age (p=0.024) as predictive factors of acute
      bowel inflammation. CONCLUSIONS: T2-w FRFSE-sequences can depict CD lesions and
      help to assess the inflammation activity, even with improved accuracy as compared
      to contrast-enhanced T1-w sequences.

PMID- 22405166
TI  - A chronic care model significantly decreases costs and healthcare utilisation in
      patients with inflammatory bowel disease.
AB  - INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic condition, yet the
      model of care is often reactive. We sought to examine whether a formal IBD
      service (IBDS) reduced inpatient healthcare utilisation or lowered costs for
      inpatient care. MATERIAL AND METHODS: With protocols, routine nurse phone follow
      up a help-line, more proactive care was delivered, with many symptoms and
      concerns dealt with prior to routine presentation. Over two five month periods
      before (2007/8) and after (2009/10) introducing a formal IBDS two discrete
      cohorts of admitted IBD patients were identified at a single centre. Each patient
      was assigned five contemporaneously admitted, age and gender matched controls.
      Inpatient healthcare utilisation was compared between patients and controls and
      disease-specific factors amongst the two IBD cohorts. RESULTS: The initial audit
      captured 102 admitted IBD patients (510 controls, median age 44 years, 57%
      female); the second audit 95 patients (475 controls, median age 46 years, 45.3%
      female). In 2009/10, the number of admissions was lower in IBD patients than in
      controls (mean 1.53+/-1.03 vs. 2.54+/-2.35; p<0.0001). This contrasts with the
      first audit, where IBD patients had more admissions than controls. Following IBDS
      introduction, the mean total cost of inpatient care was lower for IBD patients
      than controls (US$12,857.48 (US$15,236.79) vs. US$ 30,467.78 (US$ 53,760.20),
      p=0.005). In addition, patients known to a specialist gastroenterologist (GE) and
      the IBD Service tended to have the lowest mean number of admissions (GE and IBDS
      1.14 (+/-0.36) vs. no GE/IBDS 1.64 (+/-1.25)). CONCLUSIONS: Healthcare
      utilisation and disease burden in IBD decreased significantly since introducing
      an IBDS. These data suggest that proactive management improved outcomes. Contact
      with a gastroenterologist and IBDS seemed to give best results.

PMID- 22405167
TI  - Endoscopic ultrasound for perianal Crohn's disease: disease and fistula
      characteristics, and impact on therapy.
AB  - BACKGROUND AND AIM: Appropriate treatment of perianal fistulas in Crohn's disease
      (CD) involves accurate anatomic evaluation. EUS is an accepted imaging method for
      this purpose. The aim of the current study was to evaluate the clinical and
      endosonographic characteristics of perianal fistula in CD and to assess its
      impact on therapy. METHODS: All CD patients referred to the Sheba medical center
      from June 2004 to August 2008 for EUS examination of perianal fistulas were
      included. Perianal fistulas were diagnosed based on a clinical examination
      revealing at least one perianal cutaneous orifice. Demographic, clinical and
      therapeutic data was obtained. EUS was performed using an ultrasound scanner
      producing a 360 degrees  cross sectional image of the anal sphincters. RESULTS:
      Fifty six patients were included in the study. Four patients were excluded from
      the final analysis: 3 because no fistula could be detected by EUS, and one due to
      inability to tolerate the examination. The mean CD duration was 10+/-9.16 years
      (range 1-37). Mean perianal disease duration was 5.3+/-6.5 (range 1-29) years. 27
      patients had perianal involvement at presentation. Among the fistulas diagnosed,
      13 were simple (25%) and 39 were (75%) complex. No correlation was found between
      CD duration or location, patients' age and gender or fistula location with
      fistula type or complexity. EUS results influenced patient management in 86% of
      the patients. CONCLUSIONS: CD-associated perianal fistulas are mainly complex.
      EUS is a well tolerated and informative imaging modality, with significant impact
      on treatment.

PMID- 22405168
TI  - The role of in vitro interferongamma-release assay in differentiating intestinal
      tuberculosis from Crohn's disease in China.
AB  - AIM: Intestinal tuberculosis (ITB) and Crohn's disease (CD) have overlapping
      clinical, radiographic, endoscopic and histologic features, which makes the
      distinction between these two disease entities a great challenge in tuberculosis
      endemic countries. The aim of the study was to investigate the value of in vitro
      interferongamma release assay (T-SPOT.TB) in differentiating ITB from CD.
      METHODS: From June 2008 to February 2010, a total of 93 consecutive patients with
      undetermined ITB or CD were prospectively recruited. Clinical, endoscopic,
      histologic and therapeutic responses were longitudinally monitored at follow-up
      evaluation until the final definite diagnosis has been reached. RESULTS: After a
      median of 6 months' follow-up (interquartile range [IQR], 3.0 to 7.5 months),
      definitive diagnosis was achieved in 84 of the 93 patients (90%), with 19 having
      ITB and 65 having CD. On univariate analysis, a long duration of illness, chronic
      diarrhea, and anemia were significantly more common in CD (P<0.05). While night
      sweat, ascites, pulmonary lesions, circumferential ulcer on endoscopy, ileo-cecal
      valve involvement and epithelioid granulomas were significantly more common in
      ITB (P<0.05). On multivariate analysis, T-SPOT.TB (Hazard ratio 7.0, 95%
      confidence interval [CI] 1.9-25.7) was found to be a good predictor for ITB
      diagnosis. The sensitivity, specificity, positive predictive value (PPV),
      negative predictive value (NPV) of T-SPOT.TB were 84.2%, 75.4%, 50.0%, and 94.2%,
      respectively. CONCLUSIONS: When differentiating ITB and CD in tuberculosis
      endemic regions, T-SPOT.TB blood test may be a helpful and practical diagnostic
      tool for its high NPV to rule out ITB.

PMID- 22405169
TI  - Risk factors for inflammatory bowel diseases according to the "hygiene
      hypothesis": a case-control, multi-centre, prospective study in Southern Italy.
AB  - BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory
      bowel diseases (IBD) of unknown aetiology. The 'hygiene hypothesis' (HH) suggests
      that several hygiene-related factors may have contributed to the increased
      incidence of IBD. The aim of the study was to evaluate risk factors for IBD
      related to HH in a cohort of IBD patients from the south of Italy. METHODS: We
      prospectively performed a one-year, questionnaire-based, case-control, multi
      centre study focusing on the principal risk factors for IBD according to HH. We
      investigated the main surrogate markers of HH (helmintic infections and
      antibiotics in childhood; breastfeeding; family size/sibship;urban upbringing;
      personal and domestic hygiene in childhood) in UC and CD patients, in comparison
      with a control group of healthy subjects. In addition, the traditional risk
      factors for IBD were also recorded. RESULTS: The study population included 527
      cases of UC, 468 CD and 562 controls. None of the surrogate risk factors of HH
      was significantly associated with IBD. On the contrary, the traditional risk
      factors confirmed their statistical significance in this IBD population. Familial
      aggregation: OR 4.07 for UC; OR 4.83 for CD; smoking: OR 0.38 for UC; OR 1.40 for
      CD; appendectomy: OR 0.28 for UC; OR 1.61 for CD. CONCLUSION: Even though risk
      factors associated to the HH have been proposed as a possible explanation for the
      increasing calendar trend of IBD incidence, their role does not appear to be
      statistically significant. Familial aggregation, smoking habits and appendectomy
      still remain the main risk factors associated with IBD.

PMID- 22405170
TI  - Clostridium difficile infection is associated with worse long term outcome in
      patients with ulcerative colitis.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is becoming prevalent in
      general population as well as in patients with inflammatory bowel disease (IBD).
      AIM: The aim of the study was to investigate the long-term impact of CDI in
      patients with ulcerative colitis (UC). METHODS: UC inpatients or outpatients who
      had positive results for stool C. difficile toxins A and B between 2002 and 2007
      were identified (N=45). The 45 patients were matched for age and gender to UC
      patients who were negative for C. difficile and had never been diagnosed with CDI
      (N=101). The primary Colectomy within 12 months of C. difficile testing was the
      primary outcome patients with CDI and no-CDI. RESULTS: Forty-five patients were
      CDI positive and 101 were negative. Patients who were CDI positive had
      significantly more UC-related emergency room visits in the year following initial
      infection (37.8% vs. 4%, p<0.001) than those without CDI. One year following the
      index infection admission, CDI patients also had a significantly higher rate of
      colectomy than controls (35.6% vs. 9.9%, p<0.001). Among patients with CDI, 55.8%
      of patients had an escalation in medical treatment in the year after CDI as
      compared to the prior year of 12.9%, p<0.0001. CDI (odds ratio (OR) 10.0, 95%
      confidence interval CI: 2.7, 36.3, p<0.001) and severe disease on endoscopy (OR
      16.7, 95% (CI): 4.1, 67.9, p<0.001) were found to be independently associated
      with colectomy within 1 year on logistic regression analyses. CONCLUSIONS: CDI
      appears to be associated with escalation of medical therapy in the year following
      infection. CDI and severe disease on endoscopy appear to be associated with an
      increased risk for subsequent colectomy on long-term follow up.

PMID- 22405171
TI  - The effects of anti-TNF-alpha treatment with adalimumab on growth in children
      with Crohn's disease (CD).
AB  - INTRODUCTION: Adalimumab is used to treat children with Crohn's disease (CD), but
      the effects of adalimumab on growth in CD have not been studied. AIM: To study
      growth and disease activity over 12 months (6 months prior to (T-6), baseline
      (T0) and for 6 months following (T+6) adalimumab). SUBJECTS AND METHODS: Growth
      and treatment details of 36 children (M: 22) who started adalimumab at a median
      (10th, 90th) age of 14.7 years (11.3, 16.8) were reviewed. RESULTS: Of 36 cases,
      28 (78%) went into remission. Overall 42% of children showed catch up growth,
      which was more likely in: (i) those who achieved remission (median change in
      height SDS (DeltaHtSDS) increased from -0.2 (-0.9, 1.0) at T0 to 0.2 (-0.6, 1.6)
      at T+6, (p=0.007)), (ii) in those who were on immunosuppression DeltaHtSDS
      increased from -0.2 (-0.9, 1.0) at T0 to 0.1 (-0.8, 1.3) at T+6, (p=0.03) and
      (iii) in those whose indication for using adalimumab therapy was an allergic
      reaction to infliximab, median DeltaHtSDS increased significantly from -0.3 (
      0.9, 1.0) at T0 to 0.3 (-0.5, 1.6) at T+6, (p=0.02). Median DeltaHtSDS also
      increased from -0.4 (-0.8, 0.7) at T0 to 0.0 (-0.6, 1.6) at T+6, (p=0.04) in 15
      children who were on prednisolone therapy when starting adalimumab. CONCLUSION:
      Clinical response to adalimumab therapy is associated with an improvement in
      linear growth in a proportion of children with CD. Improved growth is more likely
      in patients entering remission and on immunosuppression but is not solely due to
      a steroid sparing effect.

PMID- 22405173
TI  - Fibromuscular dysplasia mimicking Crohn's disease over a period of 23 years.
AB  - Rare diseases with similar clinical presentation as more frequent
      gastrointestinal disorders might be challenging in the diagnostic and therapeutic
      management. In this case we report on a 47-year-old woman who was thought to
      suffer from Crohn's disease. Symptoms, macroscopic and histological aspects of
      the gastrointestinal tract, treatment response and clinical course had encouraged
      the wrong diagnosis over a period of 23 years. After the patient died in the
      context of a sudden clinical deterioration, fibromuscular dysplasia of the aorta
      was finally unmasked by post-mortem examination as underlying cause of all
      symptoms attributed to Crohn's disease. Re-evaluation of former diagnostic
      procedures revealed subtle aspects of fibromuscular dysplasia, even in biopsy
      samples from 23 years ago. This first case report of fibromuscular dysplasia of
      the aorta documents a rare pitfall in the diagnostic workup of a frequent
      clinical presentation in gastroenterology.

PMID- 22405172
TI  - Complementary and alternative medicine in patients with inflammatory bowel
      disease: the results of a population-based inception cohort study (IBSEN).
AB  - BACKGROUND AND AIMS: The use of complementary and alternative medicine (CAM) has
      been increasing in recent decades. Our aim was to determine the proportion of CAM
      use among patients with inflammatory bowel disease (IBD) in a longitudinal,
      population-based cohort and to identify predictive factors for CAM use. METHODS:
      The Inflammatory Bowel South-Eastern Norway (IBSEN) study is a population-based
      IBD cohort that has been followed prospectively for 10 years. The ten-year follow
      up was conducted from 2000 to 2004 and included a questionnaire regarding CAM, a
      structured interview, a review of hospital records, a clinical examination,
      laboratory tests, and an ileocolonoscopy. RESULTS: Of the 620 patients evaluated
      at the ten-year follow-up, 517 (84%) completed the CAM questionnaire, 353 had
      ulcerative colitis (UC), 164 had Crohn's disease (CD), and 50% were male. Thirty
      percent reported the use of CAM at some point since their IBD diagnosis, and 7.5%
      reported current CAM use. More CD patients than UC patients reported CAM use (38%
      vs. 27%, respectively; p=0.01). Younger age, female gender, and higher education
      level predicted CAM use in UC, whereas younger age was the only predictor of CAM
      use in CD. Thirty-six percent of the CAM users were mostly satisfied or very
      satisfied with the treatment. CONCLUSION: One third of the patients in this
      population-based cohort had used CAM at some point during a ten-year disease
      course, but only 7.5% reported current CAM use. CAM use was more common in the CD
      than in the UC patients. Only socio-demographic factors, such as age, gender and
      education, predicted CAM use.

PMID- 22405174
TI  - Therapeutic infliximab drug level in a child born to a woman with ulcerative
      colitis treated until gestation week 31.
AB  - A 26 year old woman with ulcerative colitis was treated with regular infliximab
      (IFX) infusions until gestation week 31, and gave birth to a healthy child at
      gestation week 37. Maternal IFX trough level was relatively high during the
      course of pregnancy. In the infant, therapeutic level of IFX was detectable at
      week 16 after birth, but not at reassessment at week 28. Anti-IFX antibodies were
      consistently below the detection limit in the patient and in the child. This case
      illustrates that IFX is transferred through the placenta to the embryo, and may
      result in therapeutic drug levels in the newborn child despite IFX
      discontinuation in third trimester 6 weeks prior to delivery. The half life of
      IFX appeared markedly longer in infants as compared to adults. The safety of IFX
      beyond the first trimester is unknown, and this case highlights the need for
      further investigations of maternal transfer of IFX as well as the risks
      associated with IFX administrations in the second and third trimester.

PMID- 22405175
TI  - Portal vein thrombosis in inflammatory bowel diseases: a single-center case
      series.
AB  - BACKGROUND AND METHODS: Portal vein thrombosis (PVT) has been reported as a
      complication of IBD in some case reports. We describe the presentation,
      diagnostic approaches, underlying risks factors and clinical outcome of 8 IBD
      patients with PVT. CASE-SERIES: The patients presented with partial PVT (4
      patients) or portal cavernoma. Five patients had undergone surgery. In 2 patients
      portal biliopathy was diagnosed after detection of PVT. In 4 patients, the
      diagnosis of PVT was made while IBD was in remission. Five patients showed at
      least one risk factor for hypercoagulability: lupus anti-coagulant (one patient),
      increased von Willebrand factor (2 patients) or homocysteine levels (4 patients).
      Four patients received anticoagulant therapy for 6 months. None experienced other
      thrombotic events during a median of 5 years (range 2-8 years). CONCLUSION: PVT
      is a potential complication of IBD, usually associated with acquired or inherited
      risks factors for hypercoagulability and with a benign outcome.

PMID- 22405176
TI  - Gastrointestinal basidiobolomycosis in a child; an unusual fungal infection
      mimicking fistulising Crohn's disease.
AB  - BACKGROUND: Gastrointestinal basidiobolomycosis is a rare disease caused by the
      fungus Basidiobolus ranarum. It has been reported in both children and adults.
      The disease mainly affects the colon and the small bowel; however, cases of the
      stomach, liver, pancreas, and renal system being affected have been reported.
      CASE REPORT: A 2 year old boy presented with the following symptoms; abdominal
      pain, vomiting, diarrhea, fever and palpable right iliac fossa mass. Laboratory
      investigations revealed elevated inflammatory markers and peripheral
      eosinophilia. Colonoscopy showed severely inflamed mucosa of the terminal ileum,
      cecum and ascending colon. CT scan of the abdomen demonstrated an inflammatory
      mass with wall thickening of the terminal ileum and the colon. Surgical
      exploration demonstrated retroperitoneal mass and inflamed terminal ileum, cecum
      and ascending colon. Upon laparotomy, multiple internal fistulas involving the
      bowel loops, the urinary bladder, the right ureter and the gallbladder were
      observed. Further investigations using histopathology of the resected diseased
      bowel showed extensive necrosis, multinucleated giant cells and numerous
      eosinophils and large fungal hyphae surrounded by strongly eosinophilic material
      were seen in the tissue suggestive of B. ranarum infection. The patient responded
      well to treatment with voriconazole. CONCLUSION: Gastrointestinal
      basidiobolomycosis should be considered in the differential diagnosis of every
      child presenting with abdominal pain, fever and palpable abdominal mass with
      peripheral eosinophilia. The presence of bowel inflammation and fistulas should
      not preclude such diagnosis.

PMID- 22405177
TI  - Results of the 2nd scientific workshop of the ECCO (III): basic mechanisms of
      intestinal healing.
AB  - The second scientific workshop of the European Crohn's and Colitis Organization
      (ECCO) focused on the relevance of intestinal healing for the disease course of
      inflammatory bowel disease (IBD). The objective was to better understand basic
      mechanisms, markers for disease prediction, detection and monitoring of
      intestinal healing, impact of intestinal healing on the disease course of IBD as
      well as therapeutic strategies. The results of this workshop are presented in
      four separate manuscripts. This section describes basic mechanisms of intestinal
      healing, identifies open questions in the field and provides a framework for
      future studies.

PMID- 22405178
TI  - Synchronous colorectal carcinoma in segmental colitis associated with
      diverticulosis.

PMID- 22405179
TI  - The image of mass destruction inevitably leads to intellectual mass distraction.

PMID- 22405180
TI  - Much is still to be learned about pathogenic Mycobacteria.

PMID- 22405182
TI  - Mycobacterium avium paratuberculosis and Crohn's Disease: an association
      requiring more research.

PMID- 22405183
TI  - Ectopic spleen presenting as an abdominal mass in a patient with Crohn's disease.

PMID- 22405184
TI  - Exacerbation of Crohn's disease as paradoxical effect of infliximab.

PMID- 22405185
TI  - Heritable patterns of tooth decay in the permanent dentition: principal
      components and factor analyses.
AB  - BACKGROUND: Dental caries is the result of a complex interplay among
      environmental, behavioral, and genetic factors, with distinct patterns of decay
      likely due to specific etiologies. Therefore, global measures of decay, such as
      the DMFS index, may not be optimal for identifying risk factors that manifest as
      specific decay patterns, especially if the risk factors such as genetic
      susceptibility loci have small individual effects. We used two methods to extract
      patterns of decay from surface-level caries data in order to generate novel
      phenotypes with which to explore the genetic regulation of caries. METHODS: The
      128 tooth surfaces of the permanent dentition were scored as carious or not by
      intra-oral examination for 1,068 participants aged 18 to 75 years from 664
      biological families. Principal components analysis (PCA) and factor analysis
      (FA), two methods of identifying underlying patterns without a priori surface
      classifications, were applied to our data. RESULTS: The three strongest caries
      patterns identified by PCA recaptured variation represented by DMFS index
      (correlation, r = 0.97), pit and fissure surface caries (r = 0.95), and smooth
      surface caries (r = 0.89). However, together, these three patterns explained only
      37% of the variability in the data, indicating that a priori caries measures are
      insufficient for fully quantifying caries variation. In comparison, the first
      pattern identified by FA was strongly correlated with pit and fissure surface
      caries (r = 0.81), but other identified patterns, including a second pattern
      representing caries of the maxillary incisors, were not representative of any
      previously defined caries indices. Some patterns identified by PCA and FA were
      heritable (h(2) = 30-65%, p = 0.043-0.006), whereas other patterns were not,
      indicating both genetic and non-genetic etiologies of individual decay patterns.
      CONCLUSIONS: This study demonstrates the use of decay patterns as novel
      phenotypes to assist in understanding the multifactorial nature of dental caries.

PMID- 22405186
TI  - Prophylactic treatment of migraine; the patient's view, a qualitative study.
AB  - BACKGROUND: Prophylactic treatment is an important but under-utilised option for
      the management of migraine. Patients and physicians appear to have reservations
      about initiating this treatment option. This paper explores the opinions, motives
      and expectations of patients regarding prophylactic migraine therapy. METHODS: A
      qualitative focus group study in general practice in the Netherlands with twenty
      patients recruited from urban and rural general practices. Three focus group
      meetings were held with 6-7 migraine patients per group (2 female and 1 male
      group). All participants were migraine patients according to the IHS
      (International Headache Society); 9 had experience with prophylactic medication.
      The focus group meetings were analysed using a general thematic analysis.
      RESULTS: For patients several distinguished factors count when making a decision
      on prophylactic treatment. The decision of a patient on prophylactic medication
      is depending on experience and perspectives, grouped into five categories, namely
      the context of being active or passive in taking the initiative to start
      prophylaxis; assessing the advantages and disadvantages of prophylaxis;
      satisfaction with current migraine treatment; the relationship with the physician
      and the feeling to be heard; and previous steps taken to prevent migraine.
      CONCLUSION: In addition to the functional impact of migraine, the decision to
      start prophylaxis is based on a complex of considerations from the patient's
      perspective (e.g. perceived burden of migraine, expected benefits or
      disadvantages, interaction with relatives, colleagues and physician). Therefore,
      when advising migraine patients about prophylaxis, their opinions should be taken
      into account. Patients need to be open to advice and information and intervention
      have to be offered at an appropriate moment in the course of migraine.

PMID- 22405188
TI  - Chromatin modification and remodelling: a regulatory landscape for the control of
      Arabidopsis defence responses upon pathogen attack.
AB  - Due to their sessile lifestyle, plants have to cope with an ever-changing
      environment and to defend themselves against a multitude of biotic aggressors
      that compromise their development and reproduction. Responses to various biotic
      stresses largely depend on the plant's capacity to modulate rapidly and
      specifically its transcriptome. In a stress type-dependent manner, external
      signals are translocated into the nucleus to activate transcription factors,
      resulting in the increased expression of particular sets of defence-related
      genes. Among mechanisms of transcriptional regulation, chromatin remodelling
      accomplished through the activity of histone-modifying enzymes and ATP-dependent
      chromatin-remodelling complexes is emerging as a key process in the orchestration
      of plant biotic stress responses. In this review, we summarize and discuss roles
      that chromatin-remodelling mechanisms may play in regulating Arabidopsis defence
      responses.

PMID- 22405187
TI  - Breastfeeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.
AB  - INTRODUCTION: Breastfeeding has been inversely related to breast cancer risk in
      the general population. Clarifying the role of breastfeeding among women with a
      BRCA1 or BRCA2 mutation may be helpful for risk assessment and for
      recommendations regarding prevention. We present an updated analysis of
      breastfeeding and risk of breast cancer using a large matched sample of BRCA
      mutation carriers. METHODS: We conducted a case-control study of 1,665 pairs of
      women with a deleterious mutation in either BRCA1 (n = 1,243 pairs) or BRCA2 (n =
      422 pairs). Breast cancer cases and unaffected controls were matched on year of
      birth, mutation status, country of residence and parity. Information about
      reproductive factors, including breastfeeding for each live birth, was collected
      from a routinely administered questionnaire. Conditional logistic regression was
      used to estimate the association between ever having breastfed, as well as total
      duration of breastfeeding, and the risk of breast cancer. RESULTS: Among BRCA1
      mutation carriers, breastfeeding for at least one year was associated with a 32%
      reduction in risk (OR = 0.68; 95% CI 0.52 to 0.91; P = 0.008); breastfeeding for
      two or more years conferred a greater reduction in risk (OR = 0.51; 95% CI 0.35
      to 0.74). Among BRCA2 mutation carriers, there was no significant association
      between breastfeeding for at least one year and breast cancer risk (OR = 0.83;
      95% CI 0.53 to 1.31; P = 0.43). CONCLUSIONS: These data extend our previous
      findings that breastfeeding protects against BRCA1-, but not BRCA2-associated
      breast cancer. BRCA mutation carriers should be advised of the benefit of
      breastfeeding in terms of reducing breast cancer risk.

PMID- 22405190
TI  - The human-animal interface of domestic livestock management and production and
      its relationship to brucellosis in the country of Georgia 2010: a rapid
      assessment analysis.
AB  - CONTEXT: Brucellosis is endemic in the country of Georgia, with the highest
      incidence of disease in the east of Georgia, in the Kakheti region--which is also
      home to the majority of sheep and a large portion of the national cattle herd
      (two species that are natural hosts of zoonotic Brucella spp.). OBJECTIVE: Our
      purpose was to understand the ruminant livestock management and dairy production
      as well as the sociological factors in order to relate it to the disease ecology
      of brucellosis and to understand the framework that contributes too brucellosis
      transmission in the region. METHODS: In 2010, we examined the aspects of
      livestock management and production through the use of a semi-structured
      questionnaire that was administered to 198 villagers and 41 key informants
      (physicians, veterinarians, dairy production specialists, and laboratory
      personnel) who were identified by convenience sampling. Results were primarily
      qualitative, but some were quantified to reveal trends and compared with non
      parametric tests. RESULTS: We found that animals are managed at the village
      level. Male villagers take turns shepherding and herding on both summer pastures
      (highlands) and winter pastures (lowlands or around the village). Men also do all
      the sheep-dairy production. Women care for milk cattle as well as make the dairy
      products from cow milk. Of the households that own livestock, 28% own sheep (50
      per flock) and 96% own cattle (3 per herd). The northern-most part of Kakheti
      (Akhmeta) has the widest distribution of its cheese; the guda cheese from this
      area is sold all over Kakheti and central Georgia. Typically, cheese is aged in
      20% brine for 3d (white cheeses) or 21d (guda cheeses). In addition, raw milk is
      used for cheese production and heating the milk is believed to decrease the
      quality of the final product. CONCLUSIONS: Interventions at the animal level will
      be best carried out in the fall when animals return to winter pastures. Under
      employed private veterinarians would be available for extension work and contact
      with local villagers. Control will be best achieved at the animal level because
      the local people have a social and cultural resistance to the use of heated or
      pasteurized milk for cheese production.

PMID- 22405189
TI  - Palmitoylethanolamide exerts neuroprotective effects in mixed neuroglial cultures
      and organotypic hippocampal slices via peroxisome proliferator-activated receptor
      alpha.
AB  - BACKGROUND: In addition to cytotoxic mechanisms directly impacting neurons, beta
      amyloid (Abeta)-induced glial activation also promotes release of proinflammatory
      molecules that may self-perpetuate reactive gliosis and damage neighbouring
      neurons, thus amplifying neuropathological lesions occurring in Alzheimer's
      disease (AD). Palmitoylethanolamide (PEA) has been studied extensively for its
      anti-inflammatory, analgesic, antiepileptic and neuroprotective effects. PEA is a
      lipid messenger isolated from mammalian and vegetable tissues that mimics several
      endocannabinoid-driven actions, even though it does not bind to cannabinoid
      receptors. Some of its pharmacological properties are considered to be dependent
      on the expression of peroxisome proliferator-activated receptors-alpha
      (PPARalpha). FINDINGS: In the present study, we evaluated the effect of PEA on
      astrocyte activation and neuronal loss in models of Abeta neurotoxicity. To this
      purpose, primary rat mixed neuroglial co-cultures and organotypic hippocampal
      slices were challenged with Abeta1-42 and treated with PEA in the presence or
      absence of MK886 or GW9662, which are selective PPARalpha and PPARgamma
      antagonists, respectively. The results indicate that PEA is able to blunt Abeta
      induced astrocyte activation and, subsequently, to improve neuronal survival
      through selective PPARalpha activation. The data from organotypic cultures
      confirm that PEA anti-inflammatory properties implicate PPARalpha mediation and
      reveal that the reduction of reactive gliosis subsequently induces a marked
      rebound neuroprotective effect on neurons. CONCLUSIONS: In line with our previous
      observations, the results of this study show that PEA treatment results in
      decreased numbers of infiltrating astrocytes during Abeta challenge, resulting in
      significant neuroprotection. PEA could thus represent a promising pharmacological
      tool because it is able to reduce Abeta-evoked neuroinflammation and attenuate
      its neurodegenerative consequences.

PMID- 22405191
TI  - Advances in acute kidney injury associated with cardiac surgery: the unfolding
      revolution in early detection.
AB  - Cardiac surgery-associated acute kidney injury (CSA-AKI) is important because it
      remains common and serious. A major limitation in the management of CSA-AKI has
      been ongoing delayed diagnosis by standard clinical approaches, including serum
      creatinine and calculated glomerular filtration rate. Recent advances in the
      understanding of CSA-AKI have highlighted the utility of novel biomarkers that
      diagnose CSA-AKI within the first 24 hours. The biomarkers that have been
      evaluated in clinical trials include neutrophil gelatinase-associated lipocalin
      (NGAL), cystatin C, kidney injury molecule 1 and interleukin-18. The biomarker
      with the greatest clinical promise is NGAL. Although it has multiple advantages
      over serum creatinine, it is still not the ideal biomarker for CSA-AKI. It is
      likely that a panel of early biomarkers will be developed to facilitate rapid and
      reliable detection of CSA-AKI, combining their different characteristics to
      optimize patient management. Future clinical trials likely will focus on whether
      these biomarkers predict adverse outcomes independent of serum creatinine
      fluctuations and whether therapies guided by biomarker profiles improve renal
      salvage and overall clinical outcomes. Given their clinical utility, these novel
      biomarkers have been evaluated beyond cardiac surgery for AKI in multiple
      clinical environments, including the emergency department, the operating room,
      the cardiac catheterization laboratory, and the intensive care unit. Their
      integration into clinical practice seems likely in the near future.

PMID- 22405192
TI  - An incidental finding during emergent vascular surgery: how far to go?

PMID- 22405193
TI  - Transesophageal echocardiography and noncardiac surgery: how far does the
      nondiagnostic use go?

PMID- 22405194
TI  - Identification in silico and in vitro of novel trypanosomicidal drug-like
      compounds.
AB  - Atom-based bilinear indices and linear discriminant analysis are used to discover
      novel trypanosomicidal compounds. The obtained linear discriminant analysis-based
      quantitative structure-activity relationship models, using non-stochastic and
      stochastic indices, provide accuracies of 89.02% (85.11%) and 89.60% (88.30%) of
      the chemicals in the training (test) sets, respectively. Later, both models were
      applied to the virtual screening of 18 in-house synthesized compounds to find new
      pro-lead antitrypanosomal agents. The in vitro antitrypanosomal activity of this
      set against epimastigote forms of Trypanosoma cruzi is assayed. Predictions agree
      with experimental results to a great extent (16/18) of the chemicals. Sixteen
      compounds show more than 70% of epimastigote inhibition at a concentration 100
      MUg/mL. In addition, three compounds (CRIS 112, CRIS 140 and CRIS 147) present
      more than 70% of epimastigote inhibition at a concentration of 10 MUg/mL (79.95%,
      73.97% and 78.13%, respectively) with low values of cytotoxicity (19.7%, 7.44%
      and 20.63%, correspondingly).Taking into account all these results, we could say
      that these three compounds could be optimized in forthcoming works. Even though
      none of them resulted more active than nifurtimox, the current results constitute
      a step forward in the search for efficient ways to discover new lead
      antitrypanosomals.

PMID- 22405195
TI  - A Protease TAMER: a nucleic acid-based anticoagulant.

PMID- 22405196
TI  - Biochemistry to the rescue: a ClC-2 auxiliary subunit provides a tangible link to
      leukodystrophy.
AB  - ClC-2 is a broadly distributed chloride channel with an enigmatic
      neurophysiological function. In this issue of Neuron, Jeworutzki et al. (2012)
      use a biochemical approach to identify GlialCAM, a protein with a defined link to
      leukodystrophy, as a ClC-2 auxiliary subunit.

PMID- 22405197
TI  - How do neurons sense a spike burst?
AB  - In this issue of Neuron, Xu et al. (2012) show that knock down of Syt1, a major
      Ca(2+) sensor, impairs synaptic transmission similarly in different brain regions
      but with unexpected, region-specific behavioral outcomes.

PMID- 22405198
TI  - Stop and be fair: DLPFC development contributes to social decision making.
AB  - In this issue of Neuron,Steinbeis et al. (2012) show that DLPFC structure and
      functions are associated with strategic social choices during an economic task
      and relate to impulse control abilities in both age dependent and independent
      manners.

PMID- 22405199
TI  - Imaging calcium in neurons.
AB  - Calcium ions generate versatile intracellular signals that control key functions
      in all types of neurons. Imaging calcium in neurons is particularly important
      because calcium signals exert their highly specific functions in well-defined
      cellular subcompartments. In this Primer, we briefly review the general
      mechanisms of neuronal calcium signaling. We then introduce the calcium imaging
      devices, including confocal and two-photon microscopy as well as miniaturized
      devices that are used in freely moving animals. We provide an overview of the
      classical chemical fluorescent calcium indicators and of the protein-based
      genetically encoded calcium indicators. Using application examples, we introduce
      new developments in the field, such as calcium imaging in awake, behaving animals
      and the use of calcium imaging for mapping single spine sensory inputs in
      cortical neurons in vivo. We conclude by providing an outlook on the prospects of
      calcium imaging for the analysis of neuronal signaling and plasticity in various
      animal models.

PMID- 22405200
TI  - Intercellular (mis)communication in neurodegenerative disease.
AB  - Neurodegenerative diseases have been intensively studied, but a comprehensive
      understanding of their pathogenesis remains elusive. An increasing body of
      evidence suggests that non-cell-autonomous processes play critical roles during
      the initiation and spatiotemporal progression or propagation of the dominant
      pathology. Here, we review findings highlighting the importance of pathological
      cell-cell communication in neurodegenerative disease. We focus primarily on the
      accumulating evidence suggesting dysfunctional crosstalk between neurons and
      astroglia, neurons and innate immune system cells, as well as cellular processes
      leading to transmission of pathogenic proteins between cells. Insights into the
      complex intercellular perturbations underlying neurodegeneration will enhance our
      efforts to develop effective therapeutic approaches for preventing or reversing
      symptomatic progression in this devastating class of human diseases.

PMID- 22405201
TI  - FLRT proteins are endogenous latrophilin ligands and regulate excitatory synapse
      development.
AB  - Latrophilins (LPHNs) are a small family of G protein-coupled receptors known to
      mediate the massive synaptic exocytosis caused by the black widow spider venom
      alpha-latrotoxin, but their endogenous ligands and function remain unclear.
      Mutations in LPHN3 are strongly associated with attention deficit hyperactivity
      disorder, suggesting a role for latrophilins in human cognitive function. Using
      affinity chromatography and mass spectrometry, we identify the FLRT family of
      leucine-rich repeat transmembrane proteins as endogenous postsynaptic ligands for
      latrophilins. We demonstrate that the FLRT3 and LPHN3 ectodomains interact with
      high affinity in trans and that interference with this interaction using soluble
      recombinant LPHN3, LPHN3 shRNA, or FLRT3 shRNA reduces excitatory synapse density
      in cultured neurons. In addition, reducing FLRT3 levels with shRNA in vivo
      decreases afferent input strength and dendritic spine number in dentate granule
      cells. These observations indicate that LPHN3 and its ligand FLRT3 play an
      important role in glutamatergic synapse development.

PMID- 22405202
TI  - A radial glia-specific role of RhoA in double cortex formation.
AB  - The positioning of neurons in the cerebral cortex is of crucial importance for
      its function as highlighted by the severe consequences of migrational disorders
      in patients. Here we show that genetic deletion of the small GTPase RhoA in the
      developing cerebral cortex results in two migrational disorders: subcortical band
      heterotopia (SBH), a heterotopic cortex underlying the normotopic cortex, and
      cobblestone lissencephaly, in which neurons protrude beyond layer I at the pial
      surface of the brain. Surprisingly, RhoA(-/-) neurons migrated normally when
      transplanted into wild-type cerebral cortex, whereas the converse was not the
      case. Alterations in the radial glia scaffold are demonstrated to cause these
      migrational defects through destabilization of both the actin and the
      microtubules cytoskeleton. These data not only demonstrate that RhoA is largely
      dispensable for migration in neurons but also showed that defects in radial glial
      cells, rather than neurons, can be sufficient to produce SBH.

PMID- 22405203
TI  - CYSL-1 interacts with the O2-sensing hydroxylase EGL-9 to promote H2S-modulated
      hypoxia-induced behavioral plasticity in C. elegans.
AB  - The C. elegans HIF-1 proline hydroxylase EGL-9 functions as an O(2) sensor in an
      evolutionarily conserved pathway for adaptation to hypoxia. H(2)S accumulates
      during hypoxia and promotes HIF-1 activity, but how H(2)S signals are perceived
      and transmitted to modulate HIF-1 and animal behavior is unknown. We report that
      the experience of hypoxia modifies a C. elegans locomotive behavioral response to
      O(2) through the EGL-9 pathway. From genetic screens to identify novel regulators
      of EGL-9-mediated behavioral plasticity, we isolated mutations of the gene cysl
      1, which encodes a C. elegans homolog of sulfhydrylases/cysteine synthases.
      Hypoxia-dependent behavioral modulation and H(2)S-induced HIF-1 activation
      require the direct physical interaction of CYSL-1 with the EGL-9 C terminus.
      Sequestration of EGL-9 by CYSL-1 and inhibition of EGL-9-mediated hydroxylation
      by hypoxia together promote neuronal HIF-1 activation to modulate behavior. These
      findings demonstrate that CYSL-1 acts to transduce signals from H(2)S to EGL-9 to
      regulate O(2)-dependent behavioral plasticity in C. elegans.

PMID- 22405204
TI  - Dopaminergic modulation of sucrose acceptance behavior in Drosophila.
AB  - For an animal to survive in a constantly changing environment, its behavior must
      be shaped by the complex milieu of sensory stimuli it detects, its previous
      experience, and its internal state. Although taste behaviors in the fly are
      relatively simple, with sugars eliciting acceptance behavior and bitter compounds
      avoidance, these behaviors are also plastic and are modified by intrinsic and
      extrinsic cues, such as hunger and sensory stimuli. Here, we show that dopamine
      modulates a simple taste behavior, proboscis extension to sucrose. Conditional
      silencing of dopaminergic neurons reduces proboscis extension probability, and
      increased activation of dopaminergic neurons increases extension to sucrose, but
      not to bitter compounds or water. One dopaminergic neuron with extensive
      branching in the primary taste relay, the subesophageal ganglion, triggers
      proboscis extension, and its activity is altered by satiety state. These studies
      demonstrate the marked specificity of dopamine signaling and provide a foundation
      to examine neural mechanisms of feeding modulation in the fly.

PMID- 22405205
TI  - GlialCAM, a protein defective in a leukodystrophy, serves as a ClC-2 Cl(-)
      channel auxiliary subunit.
AB  - Ion fluxes mediated by glial cells are required for several physiological
      processes such as fluid homeostasis or the maintenance of low extracellular
      potassium during high neuronal activity. In mice, the disruption of the Cl(-)
      channel ClC-2 causes fluid accumulation leading to myelin vacuolation. A similar
      vacuolation phenotype is detected in humans affected with megalencephalic
      leukoencephalopathy with subcortical cysts (MLC), a leukodystrophy which is
      caused by mutations in MLC1 or GLIALCAM. We here identify GlialCAM as a ClC-2
      binding partner. GlialCAM and ClC-2 colocalize in Bergmann glia, in astrocyte
      astrocyte junctions at astrocytic endfeet around blood vessels, and in myelinated
      fiber tracts. GlialCAM targets ClC-2 to cell junctions, increases ClC-2 mediated
      currents, and changes its functional properties. Disease-causing GLIALCAM
      mutations abolish the targeting of the channel to cell junctions. This work
      describes the first auxiliary subunit of ClC-2 and suggests that ClC-2 may play a
      role in the pathology of MLC disease.

PMID- 22405206
TI  - Repeated stress causes cognitive impairment by suppressing glutamate receptor
      expression and function in prefrontal cortex.
AB  - Chronic stress could trigger maladaptive changes associated with stress-related
      mental disorders; however, the underlying mechanisms remain elusive. In this
      study, we found that exposing juvenile male rats to repeated stress significantly
      impaired the temporal order recognition memory, a cognitive process controlled by
      the prefrontal cortex (PFC). Concomitantly, significantly reduced AMPAR- and
      NMDAR-mediated synaptic transmission and glutamate receptor expression were found
      in PFC pyramidal neurons from repeatedly stressed animals. All these effects
      relied on activation of glucocorticoid receptors and the subsequent enhancement
      of ubiquitin/proteasome-mediated degradation of GluR1 and NR1 subunits, which was
      controlled by the E3 ubiquitin ligase Nedd4-1 and Fbx2, respectively. Inhibition
      of proteasomes or knockdown of Nedd4-1 and Fbx2 in PFC prevented the loss of
      glutamatergic responses and recognition memory in stressed animals. Our results
      suggest that repeated stress dampens PFC glutamatergic transmission by
      facilitating glutamate receptor turnover, which causes the detrimental effect on
      PFC-dependent cognitive processes.

PMID- 22405207
TI  - Methamphetamine-evoked depression of GABA(B) receptor signaling in GABA neurons
      of the VTA.
AB  - Psychostimulants induce neuroadaptations in excitatory and fast inhibitory
      transmission in the ventral tegmental area (VTA). Mechanisms underlying drug
      evoked synaptic plasticity of slow inhibitory transmission mediated by GABA(B)
      receptors and G protein-gated inwardly rectifying potassium (GIRK/Kir(3))
      channels, however, are poorly understood. Here, we show that 1 day after
      methamphetamine (METH) or cocaine exposure both synaptically evoked and baclofen
      activated GABA(B)R-GIRK currents were significantly depressed in VTA GABA neurons
      and remained depressed for 7 days. Presynaptic inhibition mediated by GABA(B)Rs
      on GABA terminals was also weakened. Quantitative immunoelectron microscopy
      revealed internalization of GABA(B1) and GIRK2, which occurred coincident with
      dephosphorylation of serine 783 (S783) in GABA(B2), a site implicated in
      regulating GABA(B)R surface expression. Inhibition of protein phosphatases
      recovered GABA(B)R-GIRK currents in VTA GABA neurons of METH-injected mice. This
      psychostimulant-evoked impairment in GABA(B)R signaling removes an intrinsic
      brake on GABA neuron spiking, which may augment GABA transmission in the
      mesocorticolimbic system.

PMID- 22405208
TI  - Distinct neuronal coding schemes in memory revealed by selective erasure of fast
      synchronous synaptic transmission.
AB  - Neurons encode information by firing spikes in isolation or bursts and propagate
      information by spike-triggered neurotransmitter release that initiates synaptic
      transmission. Isolated spikes trigger neurotransmitter release unreliably but
      with high temporal precision. In contrast, bursts of spikes trigger
      neurotransmission reliably (i.e., boost transmission fidelity), but the resulting
      synaptic responses are temporally imprecise. However, the relative physiological
      importance of different spike-firing modes remains unclear. Here, we show that
      knockdown of synaptotagmin-1, the major Ca(2+) sensor for neurotransmitter
      release, abrogated neurotransmission evoked by isolated spikes but only delayed,
      without abolishing, neurotransmission evoked by bursts of spikes. Nevertheless,
      knockdown of synaptotagmin-1 in the hippocampal CA1 region did not impede
      acquisition of recent contextual fear memories, although it did impair the
      precision of such memories. In contrast, knockdown of synaptotagmin-1 in the
      prefrontal cortex impaired all remote fear memories. These results indicate that
      different brain circuits and types of memory employ distinct spike-coding schemes
      to encode and transmit information.

PMID- 22405209
TI  - Linking the computational structure of variance adaptation to biophysical
      mechanisms.
AB  - In multiple sensory systems, adaptation to the variance of a sensory input
      changes the sensitivity, kinetics, and average response over timescales ranging
      from < 100 ms to tens of seconds. Here, we present a simple, biophysically
      relevant model of retinal contrast adaptation that accurately captures both the
      membrane potential response and all adaptive properties. The adaptive component
      of this model is a first-order kinetic process of the type used to describe ion
      channel gating and synaptic transmission. From the model, we conclude that all
      adaptive dynamics can be accounted for by depletion of a signaling mechanism, and
      that variance adaptation can be explained as adaptation to the mean of a
      rectified signal. The model parameters show strong similarity to known properties
      of bipolar cell synaptic vesicle pools. Diverse types of adaptive properties that
      implement theoretical principles of efficient coding can be generated by a single
      type of molecule or synapse with just a few microscopic states.

PMID- 22405210
TI  - The generation of direction selectivity in the auditory system.
AB  - Both human speech and animal vocal signals contain frequency-modulated (FM)
      sounds. Although central auditory neurons that selectively respond to the
      direction of frequency modulation are known, the synaptic mechanisms underlying
      the generation of direction selectivity (DS) remain elusive. Here we show the
      emergence of DS neurons in the inferior colliculus by mapping the three major
      subcortical auditory nuclei. Cell-attached recordings reveal a highly reliable
      and precise firing of DS neurons to FM sweeps in a preferred direction. By using
      in vivo whole-cell current-clamp and voltage-clamp recordings, we found that the
      synaptic inputs to DS neurons are not direction selective, but temporally
      reversed excitatory and inhibitory synaptic inputs are evoked in response to
      opposing directions of FM sweeps. The construction of such temporal asymmetry,
      resulting DS, and its topography can be attributed to the spectral disparity of
      the excitatory and the inhibitory synaptic tonal receptive fields.

PMID- 22405212
TI  - Impulse control and underlying functions of the left DLPFC mediate age-related
      and age-independent individual differences in strategic social behavior.
AB  - Human social exchange is often characterized by conflicts of interest requiring
      strategic behavior for their resolution. To investigate the development of the
      cognitive and neural mechanisms underlying strategic behavior, we studied
      children's decisions while they played two types of economic exchange games with
      differing demands of strategic behavior. We show an increase of strategic
      behavior with age, which could not be explained by age-related changes in social
      preferences but instead by developmental differences in impulsivity and
      associated brain functions of the left dorsolateral prefrontal cortex (DLPFC).
      Furthermore, observed differences in cortical thickness of lDLPFC were predictive
      of differences in impulsivity and strategic behavior irrespective of age. We
      conclude that egoistic behavior in younger children is not caused by a lack of
      understanding right or wrong, but by the inability to implement behavioral
      control when tempted to act selfishly; a function relying on brain regions
      maturing only late in ontogeny.

PMID- 22405213
TI  - Spanish normative studies in a young adult population (NEURONORMA young adults
      Project): norms for the Boston Naming Test and the Token Test.
AB  - INTRODUCTION: The Boston Naming Test (BNT) and the Token Test (TT) are frequently
      used in clinical practice to assess naming and comprehension. OBJECTIVE: The aim
      of this paper is to present normative data for the BNT and for the TT as part of
      the NEURONORMA young adults Project. MATERIAL AND METHODS: A total of 179 Spanish
      healthy subjects from 18 to 49 years old were evaluated. Tables to convert raw
      scores to scaled scores are provided. Age- and education- adjusted scores are
      obtained by applying linear regressions. RESULTS: The results show an effect of
      education in both tests, and a minimal effect of age and sex. CONCLUSIONS: The
      normative data obtained will be useful in the clinical evaluation of young
      Spanish adults.

PMID- 22405211
TI  - Deafening drives cell-type-specific changes to dendritic spines in a sensorimotor
      nucleus important to learned vocalizations.
AB  - Hearing loss prevents vocal learning and causes learned vocalizations to
      deteriorate, but how vocalization-related auditory feedback acts on neural
      circuits that control vocalization remains poorly understood. We deafened adult
      zebra finches, which rely on auditory feedback to maintain their learned songs,
      to test the hypothesis that deafening modifies synapses on neurons in a
      sensorimotor nucleus important to song production. Longitudinal in vivo imaging
      revealed that deafening selectively decreased the size and stability of dendritic
      spines on neurons that provide input to a striatothalamic pathway important to
      audition-dependent vocal plasticity, and changes in spine size preceded and
      predicted subsequent vocal degradation. Moreover, electrophysiological recordings
      from these neurons showed that structural changes were accompanied by functional
      weakening of both excitatory and inhibitory synapses, increased intrinsic
      excitability, and changes in spontaneous action potential output. These findings
      shed light on where and how auditory feedback acts within sensorimotor circuits
      to shape learned vocalizations.

PMID- 22405214
TI  - [Spanish normative studies in a young adult population (NEURONORMA young adults
      Project): norms for the verbal span, visuospatial span, Letter-Number Sequencing,
      Trail Making Test and Symbol Digit Modalities Test].
AB  - INTRODUCTION: Verbal and visuospatial span, Letter-Number Sequencing, Trail
      Making Test, and Symbol Digit Modalities Test are frequently used in clinical
      practice to assess attention, executive functions and memory. OBJECTIVE: In the
      present study, as part of the Spanish normative studies of NEURONORMA young
      adults Project, normative data adjusted by age and education are provided for
      digits, Corsi Block-Tapping Task, Letter-Number Sequencing, Trail Making Test,
      and Symbol Digit Modalities Test. MATERIAL AND METHODS: The sample consisted of
      179 participants from 18 to 49 years old, who were cognitively normal. Tables to
      convert raw scores to scaled scores are provided. Age and education adjusted
      scores are provided by applying linear regressions. RESULTS: Education affected
      scores in most of the attention tests; age was found to be related to the
      visuospatial span and to speed of visuomotor tracking, and there was no
      relationship as regards sex. CONCLUSIONS: The data obtained will be useful in the
      clinical evaluation of young Spanish adults.

PMID- 22405215
TI  - A minimally invasive technique for closing an iatrogenic subclavian artery
      cannulation using the Angio-Seal closure device: two case reports.
AB  - INTRODUCTION: In the two cases described here, the subclavian artery was
      inadvertently cannulated during unsuccessful access to the internal jugular vein.
      The puncture was successfully closed using a closure device based on a collagen
      plug (Angio-Seal, St Jude Medical, St Paul, MN, USA). This technique is
      relatively simple and inexpensive. It can provide clinicians, such as intensive
      care physicians and anesthesiologists, with a safe and straightforward
      alternative to major surgery and can be a life-saving procedure. CASE
      PRESENTATION: In the first case, an anesthetist attempted ultrasound-guided
      access to the right internal jugular vein during the preoperative preparation of
      a 66-year-old Caucasian man. A 7-French (Fr) triple-lumen catheter was
      inadvertently placed into his arterial system. In the second case, an emergency
      physician inadvertently placed a 7-Fr catheter into the subclavian artery of a 77
      year-old Caucasian woman whilst attempting access to her right internal jugular
      vein. Both arterial punctures were successfully closed by means of a percutaneous
      closure device (Angio-Seal). No complications were observed. CONCLUSIONS:
      Inadvertent subclavian arterial puncture can be successfully managed with no
      adverse clinical sequelae by using a percutaneous vascular closure device. This
      minimally invasive technique may be an option for patients with non-compressible
      arterial punctures. This report demonstrates two practical points that may help
      clinicians in decision-making during daily practice. First, it provides a
      practical solution to a well-known vascular complication. Second, it emphasizes a
      role for proper vascular ultrasound training for the non-radiologist.

PMID- 22405216
TI  - Why do colonoscopy patients reject research?

PMID- 22405217
TI  - Type D (distressed) personality in primary care patients with type 2 diabetes:
      validation and clinical correlates of the DS14 assessment.
AB  - OBJECTIVE: In cardiovascular research, Type D personality (high negative
      affectivity and social inhibition) has been associated with a more than 3-fold
      increased risk of adverse health outcomes. This study examined the validity and
      clinical correlates of the Type D construct as assessed by the Type D Scale-14
      (DS14) in type 2 diabetes patients. METHODS: 1553 primary care patients with type
      2 diabetes were assessed for demographic, clinical, lifestyle and psychological
      characteristics in 2007. A subgroup (n=1012) completed the DS14 again 1 year
      later. RESULTS: The two-factor model of the Type D construct was confirmed in
      exploratory and confirmatory factor analyses; results were stable across gender.
      The Negative Affectivity (NA) and Social Inhibition (SI) subscales had adequate
      reliability in both men and women, as measured by Cronbach's alpha (NA=0.87,
      SI=0.83), lambda2 (NA=0.87/0.88, SI=0.84), corrected item-total correlations (NA
      0.47-0.77, SI 0.34-0.72) and mean inter-item correlations (NA=0.50/0.51,
      SI=0.42). One year test-retest reliability using intraclass correlation
      coefficients was 0.64/0.63 for NA and 0.73/0.65 for SI. Type D and non-Type D
      patients did not differ in vascular history or physiological risk factors, but
      Type D women had a more sedentary lifestyle (p=.003). Type D patients experienced
      less social support and more stressful life events, loneliness, and more
      depressed mood, anhedonia and anxiety (p<.001 for most variables). These
      differences were clinically significant (Cohen's d>0.60 for most variables).
      CONCLUSION: Type D personality can be reliably assessed in primary care patients
      with type 2 diabetes, and is associated with increased loneliness, stress and
      emotional distress in these patients.

PMID- 22405218
TI  - Multi-method analysis of the internal structure of the Type D Scale-14 (DS14).
AB  - OBJECTIVE: The Type D Scale-14 (DS14) measures distressed (also, Type D)
      personality by assessing the medium-level trait negative affectivity that
      encompasses the low-level traits dysphoria, anxiety, and irritability, and the
      medium-level trait social inhibition that encompasses the low-level traits social
      discomfort, reticence, and lack of social poise. The literature discusses three
      different structural models of the DS14. The goal of this study was to
      investigate which of the three models best describes the internal structure of
      the DS14. METHOD: We used three methods to investigate the internal structure of
      the DS14 items using data collected in representative samples from the Dutch
      general population (N=3,181). The methods were exploratory factor analysis,
      confirmatory factor analysis, and Mokken scale analysis. RESULTS: Exploratory
      factor analysis suggested a two-factor structure without evidence of the low
      level factors, and the other two methods showed evidence of a three-level
      structure including the low-level factors. CONCLUSIONS: A two-factor model with
      correlated errors for items defining low-level traits adequately describes the
      data. The results support the three-level hierarchical model as a conceptual
      model for Type D personality, and support the interpretation of DS14 scores on
      item subsets representing medium-level traits and low-level traits.

PMID- 22405219
TI  - Alexithymia in children with cancer and their siblings.
AB  - OBJECTIVE: The purpose of this study was to examine the levels of alexithymia in
      children with cancer, in siblings of children with cancer, and in healthy
      controls. METHOD: In order to compare the groups the Alexithymia Questionnaire
      for Children was used. The study group consisted of 97 children with cancer, 95
      siblings, and 151 healthy controls. RESULTS: The highest level of alexithymia was
      reported by children diagnosed with cancer, followed by their siblings. Healthy
      controls reported the lowest level of alexithymia. No gender differences were
      observed. The intensity of cancer was a significant predictor of the alexithymia
      score, with patients with the most severe cancers reporting the highest levels of
      alexithymia. No differences were found between the patients with moderately
      severe and least severe cancers. CONCLUSIONS: Not only children with cancer, but
      also their siblings show significantly more alexithymia than their healthy
      counterparts. Professionals should aim at preventing or reducing the
      psychological problems in both patients and their siblings.

PMID- 22405220
TI  - Cigarette smoking and mood disorders in U.S. adolescents: sex-specific
      associations with symptoms, diagnoses, impairment and health services use.
AB  - OBJECTIVE: To report sex-specific associations between cigarette smoking and DSM
      IV disorders, symptoms, and mental health services use related to depression and
      anxiety in a nationally representative sample of U.S. adolescents. METHODS: Data
      on two samples were drawn from the 1999-2004 National Health and Nutrition
      Examination Surveys to examine the association of ever smoking (versus never
      smoking) with depression (n=1884 12-15 year-olds) and anxiety (n=6336 12-19 year
      olds). Sex-specific associations between smoking and DSM-IV diagnoses,
      subthreshold and severe disorder, symptoms, impairment and mental health services
      use were assessed using logistic regression modeling. RESULTS: Rates of DSM-IV
      depression and anxiety were increased in adolescent female ever smokers as
      compared to never smokers (OR=3.9, 95% CI: 1.3-11.3 and OR=10.6, 95% CI: 3.1
      37.0, respectively). Females also showed statistically significant increases in
      severe disorder, subthreshold disorder, all symptoms of major depressive
      disorder, most symptoms of panic disorder, and increases in severe impairment,
      especially those related to schoolwork and teachers. Male adolescents showed
      smaller variations in depression and anxiety by smoking status, but were more
      likely to seek mental health services. CONCLUSIONS: Smoking prevention efforts
      may benefit from specifically targeting female youth who show signs of depression
      or anxiety diagnoses through a school-based program, while greater benefits with
      males may be evident through programs integrated into mental health services.

PMID- 22405221
TI  - Effect of obstructive sleep apnea on response to cognitive behavior therapy for
      depression after an acute myocardial infarction.
AB  - OBJECTIVE: To determine whether obstructive sleep apnea (OSA) interferes with
      cognitive behavior therapy (CBT) for depression in patients with coronary heart
      disease. METHODS: Patients who were depressed within 28 days after an acute
      myocardial infarction (MI) were enrolled in the Enhancing Recovery in Coronary
      Heart Disease (ENRICHD) trial; 289 (12%) of the 2481 participants in ENRICHD met
      the criteria for inclusion in this ancillary study. RESULTS: A validated
      ambulatory ECG algorithm was used to detect OSA. Of the 289 participants, 64
      (22%) met the criteria for OSA. CBT was efficacious relative to usual care (UC)
      for depression (p=.004). OSA had no effect on 6-month Beck Depression Inventory
      (BDI) scores (p=.11), and there was no interaction between OSA and treatment
      (p=.42). However, the adjusted mean (s.e.) 6-month BDI scores among patients
      without OSA were 12.2 (0.8) vs. 9.0 (0.8) in the UC and CBT groups (Cohen's
      d=.40); among those with OSA, they were 9.5 (1.4) and 8.1 (1.5) in the UC and CBT
      groups (d=.17). There were no significant OSA*Treatment interactions in the major
      depression (n=131) or minor depression (n=158) subgroups, but in those with major
      depression, there was a larger treatment effect in those without (d=.44) than
      with (d=.09) OSA. In those with minor depression, the treatment effects were
      d=.37 and d=.25 for the non-OSA and OSA subgroups. CONCLUSION: CBT is efficacious
      for depression after an acute myocardial infarction in patients without
      obstructive sleep apnea, but it may be less efficacious for post-MI patients with
      OSA.

PMID- 22405222
TI  - Psychological stress as a risk factor for postoperative keloid recurrence.
AB  - OBJECTIVE: To investigate psychological stress on the prognosis of the
      postoperative recurrence of keloids. METHODS: Patients with keloids (n=25),
      candidates for surgical resection and postoperative radiotherapy, had their
      psychological stress evaluated on the day before the surgical procedure. The
      parameters evaluated were pain and itching (Visual Numerical Scale), quality of
      life (Questionnaire QualiFibro/Cirurgia Plastica-UNIFESP), perceived stress
      (Perceived Stress Scale), depression and anxiety (Hospital Depression and Anxiety
      Scale), salivary cortisol and minimum and maximum galvanic skin responses (GSR)
      at rest and under stress (i.e., while the questionnaires were being filled out).
      Patients were evaluated during the 3rd, 6th, 9th and 12th months of postoperative
      care. During each return visit, two experts classified the lesions as non
      recurrent and recurrent. RESULTS: The recurrence group presented the greatest
      values in GSR during a stressful situation. The chance of recurrence increased by
      34% at each increase of 1000 arbitrary units in maximum GSR during stress.
      CONCLUSION: Psychological stress influenced the recurrence of keloids.

PMID- 22405223
TI  - The diurnal salivary cortisol pattern of adolescents from families with single,
      ill and healthy parents.
AB  - OBJECTIVE: Adolescents of single and/or chronically ill parents (target groups)
      reportedly have elevated psychological stress. However, their salivary cortisol
      pattern as part of the physiological stress system has not been compared to
      controls. The aim of this study is to examine differential outcomes in the
      diurnal cortisol pattern of the target groups. METHODS: In total, 100 adolescents
      of three groups with either single, chronically ill or two healthy parents were
      compared on cortisol. Three salivary cortisol samples were taken after awakening,
      one sample at noon and one sample at 20:00 p.m. during a non-school day. Group
      differences and interaction effects between measurement (5 times), group
      membership and covariates were tested through linear mixed modeling, repeated
      measures. Covariates were children's sex and age, socioeconomic status (SES) and
      parental depression as measured with the Beck Depression Inventory. RESULTS: The
      three groups did not differ significantly concerning the amount of salivary
      cortisol, even after controlling for the covariates. The target groups had a
      lower SES than adolescents with two healthy parents. In addition, chronically ill
      parents were more depressed than single and healthy parents. Male sex and older
      age of the child, and lower parental depression were associated with increased
      cortisol values throughout the day. CONCLUSION: Research on cortisol in children
      should control for children's sex and age, and parental depression. Adolescents
      with single and/or chronically ill parents displayed a healthy pattern of diurnal
      salivary cortisol.

PMID- 22405224
TI  - Posttraumatic growth in coronary artery disease outpatients: relationship to
      degree of trauma and health service use.
AB  - OBJECTIVES: Posttraumatic growth (PTG) is frequently reported after the strike of
      a serious medical illness. The current study sought to: 1) assess the
      relationship between degree of cardiac "threat" and PTG one-year post
      hospitalization; and 2) to explore the association between PTG and healthcare
      utilization. METHODS: In a cohort study, 2636 cardiac inpatients from 11 Ontario
      hospitals completed a sociodemographic survey; clinical data were extracted from
      charts. One year later, 1717 of these outpatients completed a postal survey,
      which assessed PTG and healthcare utilization. Morbidity data were obtained
      retrospectively through probabilistic linkage to administrative data. The
      predicted risk of recurrent events for each participant was calculated using a
      logistic regression model, based on participants' sociodemographic and clinical
      characteristics. The relationship among PTG, trauma and health service use was
      examined with multiple regression models. RESULTS: Greater PTG was significantly
      related to greater predicted risk of recurrent events (p<0.001), but not the
      actual rate of recurrent events (p=0.117). Moreover, greater PTG was
      significantly related to more physician visits (p=0.006), and cardiac
      rehabilitation program enrolment (p=0.001) after accounting for predicted risk
      and sociodemographic variables. PTG was not related to urgent healthcare use.
      CONCLUSIONS: Greater PTG was related to greater objective risk of morbidity but
      not actual morbidity, suggesting that contemplation about the risk of future
      health problems may spur PTG. Moreover, greater PTG was associated with seeking
      non-urgent healthcare. Whether this translates to improved health outcomes
      warrants future study.

PMID- 22405225
TI  - Are fatigue symptoms and chronic fatigue syndrome following Q fever infection
      related to psychosocial variables?
AB  - OBJECTIVE: Fatigue is known as one of the most common long-term sequelae of Q
      fever infections. The study aimed to determine the prevalence of fatigue
      symptoms, chronic fatigue, and chronic fatigue syndrome (CFS) in a sample of
      patients who were exposed to Q fever (Coxiella burnetii) infection compared to
      controls, and to contrast Q fever patients with and without fatigue symptoms
      related to somatoform symptoms, hypochondriacal worries and beliefs, psychosocial
      complaints, and social support. METHODS: Cross-sectional study of 84 Q fever
      exposed patients from a specific region in Jena (Germany) and 85 matched controls
      using standardized questionnaires (MFI, SF-12, CDC-SI, SOMS, Whiteley Index, OQ
      45 and F-Sozu). Diagnostic interviews were performed to validate questionnaire
      results in a smaller subsample. RESULTS: Patients who were exposed to a Q fever
      infection in the past indicated more fatigue symptoms and chronic fatigue than
      controls (54.8 vs. 20%, 32.1 vs. 4.7%) but did not show more criteria for a CFS
      (1 patient in each group). Q fever patients showing fatigue symptoms revealed
      significantly higher scores in the SOMS, the Whiteley-Index, and higher
      psychosocial complaints measured with the OQ-45. Their health related Quality of
      Life was reduced, no differences were found related to perceived social support.
      CONCLUSION: Although in our sample fatigue symptoms were common among Q fever
      patients, we found no increased prevalence of CFS in contrast to several other
      studies. The combination of fatigue symptoms with other psychosocial
      symptoms/problems support the view of a biopsychosocial etiology of fatigue
      symptoms.

PMID- 22405226
TI  - Fatigue after subarachnoid haemorrhage: a systematic review.
AB  - BACKGROUND: Fatigue is common and debilitating symptom in many neurological
      disorders and it has been reported in patients after non-traumatic subarachnoid
      haemorrhage (SAH). OBJECTIVES: We undertook a systematic review to identify and
      critically appraise all published studies that have reported frequency, severity
      and time course of fatigue after SAH, the factors associated with its development
      and the impact of fatigue on patients' life after SAH. METHODS: We searched
      Medline, EMBASE, CINAHL, PsycINFO, AMED, PubMed and included in the review all
      studies published in English, recruiting at least 10 patients (> 18 years old)
      after SAH, which reported fatigue. RESULTS: We identified 13 studies (total
      number of subjects 737) meeting our inclusion criteria. The frequency of fatigue
      ranged from 31 to 90%. Fatigue remained common even several years after the
      ictus. According to some studies fatigue after SAH was associated with sleep
      disturbances, anxiety, depression, posttraumatic stress disorder, cognitive and
      physical impairment, but these could not explain all cases of fatigue. Fatigue
      reduces quality of life and life satisfaction in patients after SAH. CONCLUSIONS:
      Fatigue is common after SAH and seems to persist. Further research is needed to
      clarify its time course and identify factors associated with its development.

PMID- 22405227
TI  - The epidemiology of multiple somatic symptoms.
AB  - BACKGROUND: The risk factors for a high total somatic symptom count are unclear;
      and it is not known whether total somatic symptoms count is a predictor of
      impaired health status. METHOD: A prospective population-based cohort study in
      North West England. Randomly sampled residents (1443 participants; 58% response)
      completed questionnaires to determine number of somatic symptoms (SSI), health
      status and a wide range of risk factors; 741 completed questionnaires 1 year
      later. We used logistic regression to identify risk factors for high SSI at
      follow-up and for persistently high SSI. We used ANCOVAR and multiple regression
      to assess whether baseline SSI predicted health status at follow-up. RESULTS:
      Twenty-one percent of participants scored over 25 on the Somatic Symptom
      Inventory (SSI) at baseline and 14% at both baseline and follow-up. Risk factors
      for a persistent high SSI were: fewer than 12 years of education, separated,
      widowed or divorced status, reported psychological abuse during childhood, co
      existing medical illnesses, anxiety and depression. In multivariate analysis
      baseline SSI predicted health status (SF12 physical component score and health
      related quality of life (EuroQol)) 12 months later. Persistent high SSI was a
      clinically meaningful predictor of these outcomes. CONCLUSIONS: Our data support
      a biopsychosocial approach to somatic symptoms rather than the dualistic approach
      of identifying "medically unexplained" symptoms. The risk factors for total
      somatic symptom count were those associated with psychiatric disorders including
      physical illness. A persistent high somatic symptom count provides a readily
      measured dimension of importance in epidemiology as a predictor of health status.

PMID- 22405228
TI  - The relationship of modern health worries to depression, symptom reporting and
      quality of life in a general population survey.
AB  - OBJECTIVE: Worries about the risk to personal health from new technology and
      features of modern life have been shown to be associated with the use of health
      care services, health behaviours, mood and reporting of physical symptoms. We
      examined the frequency and nature of these concerns in a large national sample
      and the relationship of modern health worries to demographic factors, depression,
      symptom reporting and health-related quality of life. METHODS: A representative
      sample of the German population (n=2485) completed a face-to-face survey which
      included demographic information, the Modern Health Worries Scale, as well as
      measures of depression, symptom reporting, and health-related quality of life.
      RESULTS: The majority of the population reports high or extremely high concerns
      about aspects of modernity affecting their personal health, while only six
      percent reported no concerns at all. Higher levels of modern health worries were
      found in females but were not associated with income or age. Higher levels of
      modern health worries were significantly associated with depression, symptom
      reporting and lower health-related quality of life. We found the relationship
      between modern health worries and both symptom reporting and health-related
      quality of life was only partially explained by depression for most outcome
      variables, while the association between MHW and physical component (SF-12) was
      fully mediated by depression. CONCLUSIONS: Concerns about aspects of modernity
      affecting health are common in a general population sample and associated with
      depression, symptom reporting and quality of life.

PMID- 22405229
TI  - Body image, emotions and thought control strategies in body dysmorphic disorder
      compared to eating disorders and healthy controls.
AB  - OBJECTIVE: A disordered body image, emotions such as shame and disgust, and
      intrusive thoughts are described as important and interdependent features of body
      dysmorphic disorder (BDD). However, research in this field is scarce and
      knowledge is often based on clinical observation. METHODS: The present study
      examined body image dimensions, emotions, and thought control strategies in
      individuals with: BDD (n=31), anorexia nervosa (n=32), bulimia nervosa (n=34),
      and healthy controls (n=33). Assessment was based on structured diagnostic
      interviews and self-report questionnaires. RESULTS: Individuals with BDD scored
      higher on psychosocial and appearance manipulation dimensions of body image
      compared to healthy controls. Furthermore, they reported higher psychosocial
      impairment due to appearance than both eating disorder groups. In terms of
      emotions, BDD subjects reported a higher degree of negative emotions compared to
      healthy controls, whereas no differences were found in comparison to eating
      disordered patients. Individuals with BDD reported using maladaptive strategies
      such as worrying and confrontation more often than healthy controls, when
      encountering intrusive and unwanted thoughts. CONCLUSION: The results indicate
      that individuals with BDD experience substantial psychosocial impairment due to
      appearance, high levels of various negative emotions and frequently use
      maladaptive thought control strategies.

PMID- 22405230
TI  - Nurse-led liaison mental health service for older adults: service development
      using lean thinking methodology.
AB  - OBJECTIVES: Liaison Psychiatric Services for Older Adults in the UK have been
      established over the last decade, with rather divergent team composition and
      involvement. The latest documents (National Dementia Strategy, Who Cares Wins)
      set the gold standard for liaison services for older adults in England, requiring
      a proactive approach to services and integrating assessment and treatment of
      mental disorder into routine general hospital practice. This requires a physical
      presence of liaison services in the hospital, with collaboration with medical
      colleagues. METHODS: We have adopted the above strategy in a nurse-led liaison
      service working in a General District Hospital, and used the Toyota Production
      System. RESULTS: In the current study we reflect on the 5 day rapid progress
      improvement workshops event for the liaison branch of the project, and describe
      the process of identifying real situation problems for the care of the medically
      ill, the involvement of the liaison team in their clinical care, and a feedback
      on the change in practice. CONCLUSION: The novel approach of identifying areas
      for change in an ongoing nurse-led Liaison service for Older Adults resulted in
      improving access to mental health services for elderly medically ill inpatients
      and improved quality of their overall care.

PMID- 22405231
TI  - Programmed cell death in Giardia.
AB  - Programmed cell death (PCD) has been observed in many unicellular eukaryotes;
      however, in very few cases have the pathways been described. Recently the early
      divergent amitochondrial eukaryote Giardia has been included in this group. In
      this paper we investigate the processes of PCD in Giardia. We performed a
      bioinformatics survey of Giardia genomes to identify genes associated with PCD
      alongside traditional methods for studying apoptosis and autophagy. Analysis of
      Giardia genomes failed to highlight any genes involved in apoptotic-like PCD;
      however, we were able to induce apoptotic-like morphological changes in response
      to oxidative stress (H2O2) and drugs (metronidazole). In addition we did not
      detect caspase activity in induced cells. Interestingly, we did observe changes
      resembling autophagy when cells were starved (staining with MDC) and genome
      analysis revealed some key genes associated with autophagy such as TOR, ATG1 and
      ATG 16. In organisms such as Trichomonas vaginalis, Entamoeba histolytica and
      Blastocystis similar observations have been made but no genes have been
      identified. We propose that Giardia possess a pathway of autophagy and a form of
      apoptosis very different from the classical known mechanism; this may represent
      an early form of programmed cell death.

PMID- 22405232
TI  - The contribution of family climate for road safety and social environment to the
      reported driving behavior of young drivers.
AB  - Two studies examined the contribution of the new concept of "family climate for
      road safety" and several aspects of the social environment to the driving
      behavior of young drivers. Study 1 (n=120) investigated the effect of the seven
      dimensions of the family climate for road safety - Modeling, Feedback,
      Communication, Monitoring, Noncommitment, Messages, and Limits - as well as a
      general tendency to conform to authority, and peer pressure. Study 2 (n=154)
      examined the dimensions of family climate for road safety and perceived
      popularity of reckless driving among peers. The findings indicate associations
      both between the familial and the social aspects, and between these variables and
      driving styles, willingness to take risks while driving, reckless driving habits,
      and personal commitment to safe driving. Positive aspects of the parent-child
      relationship and high levels of conformity to authority were related to greater
      endorsement of the careful driving style, whereas family's noncommitment to
      safety, higher peer pressure, and lower conformity to authority were associated
      with greater endorsement of the reckless driving style. In addition, positive
      aspects of the family climate for road safety and lower perceived popularity of
      reckless driving among friends were associated with more personal commitment to
      safe driving and a lower tendency for risky driving. The discussion stresses the
      need to look at the complex set of antecedents of reckless driving among young
      drivers and addresses the practical implications of the findings for road safety.

PMID- 22405233
TI  - Age and years in practice as factors associated with needlestick and sharps
      injuries among health care workers in a Portuguese hospital.
AB  - Health care workers are attributed to the group at highest risk of occupationally
      acquired bloodborne diseases as the result of contact with blood and body fluids.
      A cross sectional study was conducted between November 2009 and February 2010 in
      the North of Portugal, to identify potential risk factors for needlestick and
      sharps injuries. A questionnaire was provided to 363 health care professionals.
      Logistic regression was used to identify risk factors associated to needlestick
      and sharps injuries, calculating odds ratio (OR) and their 95% confidence
      interval (CI). Sixty-five percent of health care workers (64.5%, 234/363)
      reported needlestick and sharps injuries in the previous 5 years. Of the injured
      workers, 74.8% were nurses. Of the total injuries reported, the commonest were
      from syringe needle unit. The multivariate logistic regression model showed that
      the strongest risk factor was having more than 10 years or more of work in health
      services (OR 3.37, 95% CI 1.82, 6.24). Another significantly related factor was
      being over 39 years-old (OR 1.94, 95% CI 1.03, 3.63). In Portugal, there is a
      lack of epidemiological evidence related to needlestick and sharps injuries.
      Considering that patients infected with hepatitis B and C virus are commonly
      encountered in the hospital environment and that the prevalence of HIV infection
      in Portugal is one of the highest in Europe, these results should be considered
      in the design of biosafety strategies at the Hospital Center.

PMID- 22405234
TI  - Relationship between types of head injury and age of pedestrian.
AB  - This paper explores the relationship between age and the different types of head
      injury received by pedestrians in traffic accidents with cars. The analysis is
      based on information collected by hospitals in England, and is supported by in
      depth case examples. The principle result is that the risk of intracranial injury
      increases with age, whilst the risk of fracture to the head or facial bones
      remains relatively constant. This agrees with previous findings for other groups
      of casualties, which have reported that that the decrease in brain size leads to
      an increase in the relative motion of the skull and brain in an impact, with a
      corresponding increase in the risk of traumatic brain injury. Intracranial
      injuries have also been found to place the greatest burden on hospitals, which
      may have implications on automotive design if prevention of these injuries is to
      be prioritised over fractures of the skull.

PMID- 22405235
TI  - Impairment of a speed management strategy in young drivers under high cognitive
      workload.
AB  - BACKGROUND: A training method known as Episodic training has shown promise in
      reducing speeding behavior in young drivers (Prabhakharan and Molesworth, 2011).
      The present study aimed to investigate how cognitive resources are utilized to
      implement this behavioral change. METHOD: 60 participants were randomly divided
      into four groups and completed a simulated training drive in Week 1 followed by a
      10km simulated test drive in Week 2. As part of the test drive, two groups were
      asked to complete a secondary task (mental arithmetic task) in addition to the
      test drive. RESULTS: The results indicated that implementing a speed management
      strategy elicited by Episodic training was successful in isolation, but came at a
      cognitive trade-off when performed in conjunction with a secondary task.
      CONCLUSION: From an applied perspective, these results suggest driver training
      programmes should compartmentalize driver training in order to reduce the
      cognitive load experienced by trainee drivers, and hence facilitate in driver
      skill acquisition.

PMID- 22405236
TI  - Marital conflict and fifth-graders' risk for injury.
AB  - BACKGROUND: Injuries are the leading cause of morbidity and mortality for
      American children. Marital conflict has been associated with a range of negative
      health outcomes, but little is known about how marital conflict may influence
      risk of injury among children. We hypothesized marital conflict would be related
      to increased youth injury risk after controlling for relevant demographic and
      parenting covariates. METHODS: A community sample of 3218 fifth-graders recruited
      from three US locales was utilized. Ordinal logistic regression models were used
      to predict the frequency of unintentional injuries from marital conflict while
      adjusting for demographics, parenting factors (nurturance, communication,
      involvement with youth), and family cohesion. RESULTS: Higher levels of marital
      conflict were associated with higher rates of injury that required professional
      medical attention (OR=1.20, 95% CI 1.06, 1.35 per standard deviation). The same
      association held after inclusion of all covariates in a multivariate ordinal
      logistic regression model. CONCLUSIONS: Parental marital conflict is associated
      with higher rates of injuries requiring professional medical attention in
      preadolescent children.

PMID- 22405237
TI  - Analysis of driver injury severity in rural single-vehicle crashes.
AB  - Rural roads carry less than fifty percent of the traffic in the United States.
      However, more than half of the traffic accident fatalities occurred on rural
      roads. This research focuses on analyzing injury severities involving single
      vehicle crashes on rural roads, utilizing a latent class logit (LCL) model.
      Similar to multinomial logit (MNL) models, the LCL model has the advantage of not
      restricting the coefficients of each explanatory variable in different severity
      functions to be the same, making it possible to identify the impacts of the same
      explanatory variable on different injury outcomes. In addition, its unique model
      structure allows the LCL model to better address issues pertinent to the
      independence from irrelevant alternatives (IIA) property. A MNL model is also
      included as the benchmark simply because of its popularity in injury severity
      modeling. The model fitting results of the MNL and LCL models are presented and
      discussed. Key injury severity impact factors are identified for rural single
      vehicle crashes. Also, a comparison of the model fitting, analysis marginal
      effects, and prediction performance of the MNL and LCL models are conducted,
      suggesting that the LCL model may be another viable modeling alternative for
      crash-severity analysis.

PMID- 22405238
TI  - Supervisor vs. employee safety perceptions and association with future injury in
      US limited-service restaurant workers.
AB  - OBJECTIVES: Many studies have found management commitment to safety to be an
      important construct of safety climate. This study examined the association
      between supervisor and employee (shared and individual) perceptions of management
      commitment to safety and the rate of future injuries in limited-service
      restaurant workers. METHODS: A total of 453 participants (34 supervisors/managers
      and 419 employees) from 34 limited-service restaurants participated in a
      prospective cohort study. Employees' and managers' perceptions of management
      commitment to safety and demographic variables were collected at the baseline.
      The survey questions were made available in three languages: English, Spanish,
      and Portuguese. For the following 12 weeks, participants reported their injury
      experience and weekly work hours. A multivariate negative binomial generalized
      estimating equation model with compound symmetry covariance structure was used to
      assess the association between the rate of self-reported injuries and measures of
      safety perceptions. RESULTS: There were no significant relationships between
      supervisor and either individual or shared employee perceptions of management
      commitment to safety. Only individual employee perceptions were significantly
      associated with future employee injury experience but not supervisor safety
      perceptions or shared employee perceptions. CONCLUSION: Individual employee
      perception of management commitment to safety is a significant predictor for
      future injuries in restaurant environments. A study focusing on employee
      perceptions would be more predictive of injury outcomes than supervisor/manager
      perceptions.

PMID- 22405239
TI  - Examining the effects of site selection criteria for evaluating the effectiveness
      of traffic safety countermeasures.
AB  - The primary objective of this paper is to describe how site selection effects can
      influence the safety effectiveness of treatments. More specifically, the goal is
      to quantify the bias for the safety effectiveness of a treatment as a function of
      different entry criteria as well as other factors associated with crash data, and
      propose a new method to minimize this bias when a control group is not available.
      The study objective was accomplished using simulated data. The proposed method
      documented in this paper was compared to the four most common types of before
      after studies: the Naive, using a control group (CG), the empirical Bayes (EB)
      method based on the method of moment (EB(MM)), and the EB method based on a
      control group (EB(CG)). Five scenarios were examined: a direct comparison of the
      methods, different dispersion parameter values of the Negative Binomial model,
      different sample sizes, different values of the index of safety effectiveness
      (theta), and different levels of uncertainty associated with the index. Based on
      the simulated scenarios (also supported theoretically), the study results showed
      that higher entry criteria, larger values of the safety effectiveness, and
      smaller dispersion parameter values will cause a larger selection bias.
      Furthermore, among all methods evaluated, the Naive and the EB(MM) methods are
      both significantly affected by the selection bias. Using a control group, or the
      EB(CG), can mutually eliminate the site selection bias, as long as the
      characteristics of the control group (truncated data for the CG method or the non
      truncated sample population for the EB(CG) method) are exactly the same as for
      the treatment group. In practice, finding datasets for the control group with the
      exact same characteristics as for the treatment group may not always be feasible.
      To overcome this problem, the method proposed in this study can be used to adjust
      the Naive estimator of the index of safety effectiveness, even when the mean and
      dispersion parameter are not properly estimated.

PMID- 22405240
TI  - Nighttime approaches to offshore installations in Brazil: Safety shortcomings
      experienced by helicopter pilots.
AB  - Accident rates for night sorties by helicopters traveling to offshore oil and gas
      platforms are at least five times higher than those during the daytime. Because
      pilots need to transition from automated flight to a manually flown night visual
      segment during arrival, the approach and landing phases cause great concern.
      Despite this, in Brazil, regulatory changes have been sought to allow for the
      execution of offshore night flights because of the rapid expansion of the
      petroleum industry. This study explores the factors that affect safety during
      night visual segments in Brazil using 28 semi-structured interviews with offshore
      helicopter pilots, followed by a template analysis of the narratives. The
      relationships among the factors suggest that flawed safety oversights, caused by
      a combination of lack of infrastructure for night flights offshore and declining
      training, currently favor spatial disorientation on the approach and near misses
      when close to the destination. Safety initiatives can be derived on the basis of
      these results.

PMID- 22405241
TI  - Management commitment to safety vs. employee perceived safety training and
      association with future injury.
AB  - OBJECTIVES: The purpose of this study is to explore and examine, specific to the
      restaurant industry, two important constructs emerging from the safety climate
      literature: employee perceptions of safety training and management commitment to
      safety. Are these two separate constructs? Are there both individual- and shared
      group-level safety perceptions for these two constructs? What are the
      relationships between these two constructs and future injury outcomes? METHODS: A
      total of 419 employees from 34 limited-service restaurants participated in a
      prospective cohort study. Employees' perceptions of management commitment to
      safety and safety training and demographic variables were collected at the
      baseline. The survey questions were made available in three languages: English,
      Spanish, and Portuguese. For the following 12 weeks, participants reported their
      injury experience and weekly work hours. A multivariate negative binomial
      generalized estimating equation model with compound symmetry covariance structure
      was used to assess the association between the rate of self-reported injuries and
      measures of safety perceptions. RESULTS: Even though results showed that the
      correlation between employees'perceived safety training and management commitment
      to safety was high, confirmatory factor analysis of measurement models showed
      that two separate factors fit the model better than as two dimensions of a single
      factor. Homogeneity tests showed that there was a shared perception of the factor
      of management commitment to safety for the restaurant workers but there was no
      consistent perception among them for the factor of perceived safety training.
      Both individual employees'perceived management commitment to safety and
      perceptions of safety training can predict employees' subsequent injuries above
      and beyond demographic variables. However, there was no significant relationship
      between future injury and employees' shared perception of management commitment
      to safety. Further, our results suggest that the variable of employees'perceived
      safety training could be a proximal predictor of future injury outcome which
      mediated the relationship between employees'perceived management commitment to
      safety (a distal predictor) and injury outcome. We propose that when employees
      perceive their management as having a high level of commitment to safety, they
      will also perceive that the safety training of the organization is good, which
      will then further predict future injury experience of the employees.

PMID- 22405242
TI  - Crash and burn? Vehicle, collision, and driver factors that influence motor
      vehicle collision fires.
AB  - A retrospective population-based case-control study was performed to determine
      the association between vehicle fires, and vehicle, collision, and driver factors
      on highways with a posted speed limit of at least 55mph. Data were obtained from
      the Kentucky Collision Report Analysis for Safer Highways (CRASH) electronic
      files for 2000-2009 from the Kentucky State Police Records Sections. The results
      from the final multiple logistic regression show that large trucks were at a
      higher risk for a collision involving a fire than passenger vehicles and pickup
      trucks. When controlling for all other variables in the model, vehicles 6 years
      old and older, driving straight down the highway, and single vehicle collisions
      were also identified as factors that increase the risk of motor vehicle collision
      fires on roadways with a posted speed limit of >=55mph. Of the 2096 vehicles that
      caught fire, there were 632 (30%) non-fatally injured drivers and 224 (11%)
      fatally injured drivers. The results of this study have the potential to inform
      public health messages directed to the transportation industry, particularly semi
      truck drivers, in regard to fire risk.

PMID- 22405243
TI  - Assessing the efficiency of priorities for traffic law enforcement in Norway.
AB  - This paper assesses the efficiency of priorities for traffic law enforcement in
      Norway. Priorities are regarded as efficient if: (1) enforcement ensures a
      sufficient level of deterrence to keep down the rate of violations; (2) selection
      of target violations for enforcement is based on the risk attributable to them;
      and (3) an optimal level of enforcement is selected, i.e. the marginal benefits
      of enforcement in terms of preventing accidents equal the marginal costs of
      enforcement. The efficiency of current traffic law enforcement in Norway is
      assessed in terms of these criteria. It is found that the risk of apprehension
      varies considerably between different traffic violations. These variations do not
      reflect the risk attributable to the violations, i.e. it is not the case that the
      risk of apprehension is higher for violations that make a large contribution to
      fatalities and injuries than for violations that make a smaller contribution. In
      principle, shifting priorities so as to increase the risk of apprehension for
      some violations and reduce it for other violations could make police enforcement
      slightly more efficient. The main finding, however, is that the current level of
      enforcement is too low. Cost-benefit analyses show that substantially increasing
      the amount of police enforcement is cost-effective.

PMID- 22405244
TI  - The impact of tunnel design and lighting on the performance of attentive and
      visually distracted drivers.
AB  - The crash risk in tunnels is lower than on the open road network, but the
      consequences of a crash are often severe. Proper tunnel design is one measure to
      reduce the likelihood of crashes, and the objective of this work is to
      investigate how driving performance is influenced by design factors, and whether
      there is an interaction with secondary task load. Twenty-eight drivers
      participated in the simulator study. A full factorial within subject design was
      used to investigate the tunnel wall colour (dark or light-coloured walls),
      illumination (three different levels) and task load (with or without a visual
      secondary task). The results show that tunnel design and illumination have some
      influence on the drivers' behaviour, but visual attention given to the driving
      task is the most crucial factor, giving rise to significant changes in both
      driving behaviour and visual behaviour. The results also indicate that light
      coloured tunnel walls are more important than strong illumination to keep the
      drivers' visual attention focused forward.

PMID- 22405245
TI  - Evaluation of the impacts of traffic states on crash risks on freeways.
AB  - The primary objective of this study is to divide freeway traffic flow into
      different states, and to evaluate the safety performance associated with each
      state. Using traffic flow data and crash data collected from a northbound segment
      of the I-880 freeway in the state of California, United States, K-means
      clustering analysis was conducted to classify traffic flow into five different
      states. Conditional logistic regression models using case-controlled data were
      then developed to study the relationship between crash risks and traffic states.
      Traffic flow characteristics in each traffic state were compared to identify the
      underlying phenomena that made certain traffic states more hazardous than others.
      Crash risk models were also developed for different traffic states to identify
      how traffic flow characteristics such as speed and speed variance affected crash
      risks in different traffic states. The findings of this study demonstrate that
      the operations of freeway traffic can be divided into different states using
      traffic occupancy measured from nearby loop detector stations, and each traffic
      state can be assigned with a certain safety level. The impacts of traffic flow
      parameters on crash risks are different across different traffic flow states. A
      method based on discriminant analysis was further developed to identify traffic
      states given real-time freeway traffic flow data. Validation results showed that
      the method was of reasonably high accuracy for identifying freeway traffic
      states.

PMID- 22405247
TI  - Scale development of safety management system evaluation for the airline
      industry.
AB  - The airline industry relies on the implementation of Safety Management System
      (SMS) to integrate safety policies and augment safety performance at both
      organizational and individual levels. Although there are various degrees of SMS
      implementation in practice, a comprehensive scale measuring the essential
      dimensions of SMS is still lacking. This paper thus aims to develop an SMS
      measurement scale from the perspective of aviation experts and airline managers
      to evaluate the performance of company's safety management system, by adopting
      Schwab's (1980) three-stage scale development procedure. The results reveal a
      five-factor structure consisting of 23 items. The five factors include
      documentation and commands, safety promotion and training, executive management
      commitment, emergency preparedness and response plan and safety management
      policy. The implications of this SMS evaluation scale for practitioners and
      future research are discussed.

PMID- 22405246
TI  - Association between cannabis use and non-traffic injuries.
AB  - BACKGROUND: This study aimed to assess the association between cannabis use and
      unintended non-fatal injuries other than those caused by road crashes. METHODS:
      Cross-sectional data were collected from a nationwide sample of 27,934 subjects
      surveyed in 2005 in Spain: 14,699 persons aged 15-34 years and 13,235 aged 35-64
      years. Logistic regression was used to obtain odds ratios (OR) between patterns
      of cannabis use and frequency of non-traffic injuries, adjusted for
      sociodemographic factors and for the use of alcohol, tobacco and other drugs.
      RESULTS: Cannabis use in the last 12 months was associated with a higher
      frequency of injuries (OR=1.4; 95% CI: 1.2-1.7). The OR in older adults (35-64
      year age group) was 1.8 and 1.3 in younger people (15-34 year age group). The
      strongest associations found were between weekly use of cannabis and injuries
      from knocks and bumps (OR=5.1; 95% CI 2.9-8.9) and those occurring outside work
      (OR=3.0; 95% CI 1.8-4.9) in the older adult population. CONCLUSION: Although our
      analysis did not control for behavioural factors, cannabis use is independently
      associated with an increased frequency of non-traffic injuries, especially in the
      older adult population. These associations emphasise the need to carry out
      longitudinal studies addressing the causal links between cannabis use and
      unintended injuries.

PMID- 22405248
TI  - Evaluation of driving ability among residents after the duty shift.
AB  - INTRODUCTION AND AIMS: Medical residents in training have long work shifts that
      lead increases the risk of traffic accidents. The Asde Driver Test is a test
      battery with equipment homologated by the Spanish traffic authorities designed to
      assess psychological and physical aptitude for obtaining the driving license in
      Spain. We study whether driving ability is objectively affected in this test.
      MATERIALS AND METHODS: The Asde Driver Test was applied before and in the morning
      after duty The data were evaluated using the SPSS statistical package, analyzing
      the variations in score with the Student t-test for paired samples. The results
      were also compared with the validated assessment criteria of the class B driving
      license test, based on passing of the cutoff points for each analyzed variable.
      Subjects with physical limitations precluding test conduction were excluded, as
      were those with a resting period during the duty shift of over 4h. RESULTS: Of
      the 25 residents, 22 cases were therefore included in the data analysis. There
      were no significant differences in the paired global pre- and post-duty
      comparison of results, though there were cases in which the results obtained
      after duty fell short of the recommended criteria for passing the aptitude test.
      COMMENTS: The Asde Driver Test includes tests relating to anticipation speed,
      bimanual visual-motor coordination, multiple reaction times, concentrated
      attention, and resistance to monotony. The results obtained show that fatigue in
      some cases, though not on a generalized basis, adversely affects skills needed
      for driving, such as reaction time, resistance to monotony, anticipation speed,
      or visual-motor coordination. In conclusion, following the resident duty shift,
      impaired driving ability is observed in some cases that could increase the risk
      of traffic accidents.

PMID- 22405249
TI  - Bringing women to the forefront of science and medicine.

PMID- 22405250
TI  - RCP should make an urgent statement against Health and Social Care Bill.

PMID- 22405252
TI  - Management of Kawasaki disease: corticosteroids revisited.

PMID- 22405253
TI  - Misoprostol for all women seeking abortion?

PMID- 22405251
TI  - Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery
      abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label,
      blinded-endpoints trial.
AB  - BACKGROUND: Evidence indicates that corticosteroid therapy might be beneficial
      for the primary treatment of severe Kawasaki disease. We assessed whether
      addition of prednisolone to intravenous immunoglobulin with aspirin would reduce
      the incidence of coronary artery abnormalities in patients with severe Kawasaki
      disease. METHODS: We did a multicentre, prospective, randomised, open-label,
      blinded-endpoints trial at 74 hospitals in Japan between Sept 29, 2008, and Dec
      2, 2010. Patients with severe Kawasaki disease were randomly assigned by a
      minimisation method to receive either intravenous immunoglobulin (2 g/kg for 24 h
      and aspirin 30 mg/kg per day) or intravenous immunoglobulin plus prednisolone
      (the same intravenous immunoglobulin regimen as the intravenous immunoglobulin
      group plus prednisolone 2 mg/kg per day given over 15 days after concentrations
      of C-reactive protein normalised). Patients and treating physicians were unmasked
      to group allocation. The primary endpoint was incidence of coronary artery
      abnormalities during the study period. Analysis was by intention to treat. This
      trial is registered with the University Hospital Medical Information Network
      clinical trials registry, number UMIN000000940. FINDINGS: We randomly assigned
      125 patients to the intravenous immunoglobulin plus prednisolone group and 123 to
      the intravenous immunoglobulin group. Incidence of coronary artery abnormalities
      was significantly lower in the intravenous immunoglobulin plus prednisolone group
      than in the intravenous immunoglobulin group during the study period (four
      patients [3%] vs 28 patients [23%]; risk difference 0.20, 95% CI 0.12-0.28,
      p<0.0001). Serious adverse events were similar between both groups: two patients
      had high total cholesterol and one neutropenia in the intravenous immunoglobulin
      plus prednisolone group, and one had high total cholesterol and another non
      occlusive thrombus in the intravenous immunoglobulin group. INTERPRETATION:
      Addition of prednisolone to the standard regimen of intravenous immunoglobulin
      improves coronary artery outcomes in patients with severe Kawasaki disease in
      Japan. Further study of intensified primary treatment for this disease in a mixed
      ethnic population is warranted. FUNDING: Japanese Ministry of Health, Labour and
      Welfare.

PMID- 22405254
TI  - The global role of kidney transplantation.

PMID- 22405255
TI  - Complications of first-trimester abortion by vacuum aspiration after cervical
      preparation with and without misoprostol: a multicentre randomised trial.
AB  - BACKGROUND: Little information is available about the incidence of complications
      from vacuum aspiration for first-trimester abortion after cervical preparation
      with prostaglandin analogues. We compared incidence of complications from vacuum
      aspiration in women who had had cervical preparation with misoprostol and those
      who had not. METHODS: We did a randomised parallel-group trial at 14 centres in
      nine countries between Oct 22, 2002, and Sept 24, 2005. Healthy women seeking
      first-trimester abortion were randomly assigned via a computer-generated
      randomisation sequence stratified by centre, to receive vaginal administration of
      either two 200 MUg tablets of misoprostol or two placebo tablets 3 h before
      abortion by vacuum aspiration. Participants and health-care personnel other than
      staff administering the treatment were masked to group assignment. Follow-up was
      up to 2 weeks. The primary outcome was one or more complications of vacuum
      aspiration (cervical tear, uterine perforation, incomplete abortion, uterine re
      evacuation, pelvic inflammatory disease, or any other serious adverse event). We
      included women undergoing treatment and vacuum aspiration in the analysis of
      immediate complications; whereas, in the analysis of delayed complications, we
      included only those followed-up. In the analysis of any immediate or delayed
      complication, we excluded women lost to follow-up. This trial is registered,
      number ISRCTN85366519. FINDINGS: We randomly assigned 2485 women to the
      misoprostol group and 2487 to the placebo group. Two women in the misoprostol
      group did not have vacuum aspiration. 56 women in each group were lost to follow
      up. 50 (2%) of 2427 women in the misoprostol group and 74 (3%) of 2431 in the
      placebo group had one or more complication of vacuum aspiration (relative risk
      [RR] 0.68, 95% CI 0.47-0.96). No women in the misoprostol group had cervical
      tears and three had uterine perforations compared with two women in the placebo
      group who had cervical tears and one who had perforation. 19 (<1%) women given
      misoprostol and 55 (2%) on placebo had incomplete abortions (0.35, 0.21-0.58), of
      whom 14 (<1%) versus 48 (2%) needed uterine re-evacuation (0.29, 0.16-0.53). We
      noted no difference between groups in incidence of pelvic inflammatory disease
      (30 [1%] vs 25 [1%]; RR 1.20, 0.71-2.04) or other serious adverse events. The
      main side-effects of misoprostol during the 3 h treatment were abdominal pain
      (1355 [55%] of 2484 women vs 545 [22%] of 2487 women in the placebo group) and
      vaginal bleeding (909 [37%] vs 167 [7%]). INTERPRETATION: Cervical preparation
      with 400 MUg of vaginal misoprostol can reduce incidence of complications from
      vacuum aspiration for first trimester abortion. FUNDING: UN Development
      Programme/UN Population Fund/WHO/World Bank Special Programme of Research,
      Development and Research Training in Human Reproduction, Department of
      Reproductive Health and Research, WHO, and the Packard Foundation.

PMID- 22405257
TI  - Intracameral mydriatics in phacoemulsification cataract surgery -- a 6-year
      follow-up.
AB  - PURPOSE: To evaluate the long-term safety of intracameral mydriatics (ICM) in
      phacoemulsification cataract surgery compared with conventional topical
      mydriatics (TM). METHODS: A total of 45 patients were examined 6 years after
      phacoemulsification cataract surgery. The patients had previously participated in
      a prospective randomized double-blind study including 60 patients, operated with
      either ICM or TM. The follow-up included best-corrected visual acuity (BCVA),
      intraocular pressure (IOP), grade of posterior capsule opacification (PCO), YAG
      laser capsulotomy rate, pupil size, corneal thickness and endothelial morphology.
      RESULTS: No differences in postoperative BCVA, IOP, pupil size, PCO or YAG rate
      were observed between the groups. Endothelial cell loss, endothelial morphology
      and corneal thickness were also equivalent. CONCLUSIONS: Intracameral mydriatics
      is a safe alternative to topical mydriatics in phacoemulsification cataract
      surgery with no long-term disadvantages at 6-year follow-up.

PMID- 22405256
TI  - Anticancer property of Bryophyllum pinnata (Lam.) Oken. leaf on human cervical
      cancer cells.
AB  - BACKGROUND: Bryophyllum pinnata (B. pinnata) is a common medicinal plant used in
      traditional medicine of India and of other countries for curing various
      infections, bowel diseases, healing wounds and other ailments. However, its
      anticancer properties are poorly defined. In view of broad spectrum therapeutic
      potential of B. pinnata we designed a study to examine anti-cancer and anti-Human
      Papillomavirus (HPV) activities in its leaf extracts and tried to isolate its
      active principle. METHODS: A chloroform extract derived from a bulk of
      botanically well-characterized pulverized B. pinnata leaves was separated using
      column chromatography with step- gradient of petroleum ether and ethyl acetate.
      Fractions were characterized for phyto-chemical compounds by TLC, HPTLC and NMR
      and Biological activity of the fractions were examined by MTT-based cell
      viability assay, Electrophoretic Mobility Shift Assay, Northern blotting and
      assay of apoptosis related proteins by immunoblotting in human cervical cancer
      cells. RESULTS: Results showed presence of growth inhibitory activity in the
      crude leaf extracts with IC50 at 552 MUg/ml which resolved to fraction F4
      (Petroleum Ether: Ethyl Acetate:: 50:50) and showed IC50 at 91 MUg/ml.
      Investigations of anti-viral activity of the extract and its fraction revealed a
      specific anti-HPV activity on cervical cancer cells as evidenced by
      downregulation of constitutively active AP1 specific DNA binding activity and
      suppression of oncogenic c-Fos and c-Jun expression which was accompanied by
      inhibition of HPV18 transcription. In addition to inhibiting growth, fraction F4
      strongly induced apoptosis as evidenced by an increased expression of the pro
      apoptotic protein Bax, suppression of the anti-apoptotic molecules Bcl-2, and
      activation of caspase-3 and cleavage of PARP-1. Phytochemical analysis of
      fraction F4 by HPTLC and NMR indicated presence of activity that resembled
      Bryophyllin A. CONCLUSIONS: Our study therefore demonstrates presence of
      anticancer and anti-HPV an activity in B. pinnata leaves that can be further
      exploited as a potential anticancer, anti-HPV therapeutic for treatment of HPV
      infection and cervical cancer.

PMID- 22405258
TI  - Duration and severity of primary sclerosing cholangitis is not associated with
      risk of neoplastic changes in the colon in patients with ulcerative colitis.
AB  - BACKGROUND: Annual surveillance colonoscopy to detect colon cancer is recommended
      for patients with primary sclerosing cholangitis (PSC) and ulcerative colitis
      (UC). Limited data currently support these recommendations. OBJECTIVE: To study
      whether a relationship exists between the severity and duration of PSC and the
      risk of colon cancer and dysplasia (colon neoplasia). DESIGN: Retrospective,
      longitudinal study. SETTING: Tertiary-care referral center. PATIENTS: Information
      pertaining to duration of PSC, UC, requirement for orthotopic liver
      transplantation, and time to diagnosis of colon neoplasia was obtained for
      patients with PSC and UC. Patients were evaluated and followed-up from 1985 to
      2011 at a single institution. MAIN OUTCOME MEASUREMENTS: Association between the
      severity and duration of PSC-UC and the time of occurrence of colon neoplasia.
      RESULTS: Of 167 patients with a combined diagnosis of PSC-UC, 55 had colonic
      neoplasia on colonoscopy. Colonic neoplasia occurred more frequently within 2
      years of a combined diagnosis of PSC-UC (6.6/100 patient-years of follow-up) than
      after 8 years from PSC-UC (2.7/100 patient-years of follow-up). On proportional
      hazards analysis, older age at PSC diagnosis (hazard ratio 1.23 for every 5
      years; 95% confidence interval, 1.03-1.34; P = .014) increased the risk of colon
      neoplasia. LIMITATIONS: Retrospective study. CONCLUSION: In this study, the
      severity of PSC was not significantly associated with the risk of colon
      neoplasia. Patients with PSC and UC have a high risk of colon neoplasia soon
      after the coexistence of the two diseases is discovered. Older age at PSC
      diagnosis increases this risk.

PMID- 22405259
TI  - Accuracy in diagnosis of allergy to beta-lactams.

PMID- 22405260
TI  - The ideal of biopsychosocial chronic care: how to make it real? A qualitative
      study among Dutch stakeholders.
AB  - BACKGROUND: Chronically ill patients often experience psychosocial problems in
      everyday life. A biopsychosocial approach is considered to be essential in
      chronic care. In Dutch primary health care the current biomedically oriented
      clinical practice may conflict with the biopsychosocial approach. This study is
      aimed to explore the views of Dutch stakeholders on achieving a biopsychosocial
      approach to the care of patients with chronic diseases. METHODS: In a qualitative
      explorative study design, we held semi-structured interviews with stakeholders,
      face-to-face or by telephone. Data were analysed using content analysis. Thirty
      representatives of Dutch patients with chronic illnesses, primary care
      professionals, policy makers, health inspectorate, health insurers, educational
      institutes and researchers were interviewed. RESULTS: Stakeholders were aware
      that a systematic biopsychosocial care approach is lacking in current practice.
      Opportunities for effective change are multidimensional. Achieving a
      biopsychosocial approach to care relates to active patient participation, the
      training of professionals, high-quality guidelines, protocols and tools,
      integrated primary care, research and financial issues. CONCLUSIONS: Although the
      principles and importance of the biopsychosocial model have been recognized, the
      provision of care that starts from the medical, emotional or social needs of
      individual patients does not fit in easily with the current Dutch health care
      system. All parties involved need to make a commitment to realize the ideal of
      biopsychosocial chronic care. Together they need to equip health professionals
      with skills to understand patients' multifaceted needs and to reward integrated
      biopsychosocial care. Patients need to be empowered to be active partners in
      their own care.

PMID- 22405261
TI  - Inflammatory monocytes damage the hippocampus during acute picornavirus infection
      of the brain.
AB  - BACKGROUND: Neuropathology caused by acute viral infection of the brain is
      associated with the development of persistent neurological deficits.
      Identification of the immune effectors responsible for injuring the brain during
      acute infection is necessary for the development of therapeutic strategies that
      reduce neuropathology but maintain immune control of the virus. METHODS: The
      identity of brain-infiltrating leukocytes was determined using microscopy and
      flow cytometry at several acute time points following intracranial infection of
      mice with the Theiler's murine encephalomyelitis virus. Behavioral consequences
      of immune cell depletion were assessed by Morris water maze. RESULTS:
      Inflammatory monocytes, defined as CD45hiCD11b++F4/80+Gr1+1A8-, and neutrophils,
      defined as CD45hiCD11b+++F4/80-Gr1+1A8+, were found in the brain at 12 h after
      infection. Flow cytometry of brain-infiltrating leukocytes collected from LysM:
      GFP reporter mice confirmed the identification of neutrophils and inflammatory
      monocytes in the brain. Microscopy of sections from infected LysM:GFP mice showed
      that infiltrating cells were concentrated in the hippocampal formation.
      Immunostaining confirmed that neutrophils and inflammatory monocytes were
      localized to the hippocampal formation at 12 h after infection. Immunodepletion
      of inflammatory monocytes and neutrophils but not of neutrophils only resulted in
      preservation of hippocampal neurons. Immunodepletion of inflammatory monocytes
      also preserved cognitive function as assessed by the Morris water maze.
      CONCLUSIONS: Neutrophils and inflammatory monocytes rapidly and robustly
      responded to Theiler's virus infection by infiltrating the brain. Inflammatory
      monocytes preceded neutrophils, but both cell types were present in the
      hippocampal formation at a timepoint that is consistent with a role in triggering
      hippocampal pathology. Depletion of inflammatory monocytes and neutrophils with
      the Gr1 antibody resulted in hippocampal neuroprotection and preservation of
      cognitive function. Specific depletion of neutrophils with the 1A8 antibody
      failed to preserve neurons, suggesting that inflammatory monocytes are the key
      effectors of brain injury during acute picornavirus infection of the brain. These
      effector cells may be important therapeutic targets for immunomodulatory or
      immunosuppressive therapies aimed at reducing or preventing central nervous
      system pathology associated with acute viral infection.

PMID- 22405263
TI  - Current challenges in type 2 diabetes.

PMID- 22405262
TI  - Therapeutic benefit of treatment of stroke with simvastatin and human umbilical
      cord blood cells: neurogenesis, synaptic plasticity, and axon growth.
AB  - The therapeutic efficacy of cell-based therapy after stroke can be enhanced by
      making the host brain tissue more receptive to the administered cells, which
      thereby facilitates brain plasticity. We hypothesized that simvastatin increases
      human umbilical cord blood cell (HUCBC) migration  into the ischemic brain and
      promotes brain plasticity and neurological functional outcome after stroke. Rats
      were subjected to 2-h middle cerebral artery occlusion (MCAo) and administered
      subtherapeutic doses of simvastatin (0.5 mg/kg, gavaged daily for 7 days), HUCBCs
      (1 * 10(6),  one time injection via tail vein), or combination simvastatin with
      HUCBCs starting at 24 h after stroke. Combination treatment of stroke showed an
      interactive effect in improvement of neurological outcome compared with
      simvastatin or HUCBC monotherapy groups. In addition, combination treatment 
      significantly increased brain-derived neurotrophic factor/TrkB expression and the
      number of engrafted HUCBCs in the ischemic brain compared with HUCBC monotherapy.
      The number of engrafted HUCBCs was significantly correlated with functional
      outcome (modified neurological severity score). Combination  treatment
      significantly increased neurogenesis and synaptic plasticity in the ischemic
      brain, and promoted neuroblast migration in cultured subventricular zone
      explants. Using primary cultured neurons (PCNs), we found that combination
      treatment enhanced neurite outgrowth compared with nontreatment  control,
      simvastatin or HUCBC supernatant monotherapy. Inhibition of TrkB significantly
      attenuated combination treatment-induced neurite outgrowth. Our data indicate
      that combination simvastatin and HUCBC treatment of stroke increases BDNF/TrkB
      expression, enhances HUCBC migration into the  ischemic brain, amplifies
      endogenous neurogenesis, synaptic plasticity and axonal growth, and thereby
      improves functional outcome after stroke.

PMID- 22405264
TI  - The design of the liraglutide clinical trial programme.
AB  - Liraglutide is a once-daily human glucagon-like peptide-1 analogue used in the
      treatment of type 2 diabetes (T2D). It has been prospectively investigated in a
      series of multinational, randomised, controlled phase 3 trials (the Liraglutide
      Effect and Action in Diabetes programme), as well as in an additional direct head
      to-head study with sitagliptin. These trials were designed to clarify the use and
      safety of liraglutide in clinical practice across the treatment continuum of T2D,
      and consequently involved a large number and diverse range of patients. These
      studies also included active comparisons against antidiabetic agents including
      metformin, rosiglitazone, glimepiride, insulin glargine, exenatide and
      sitagliptin, and therefore have helped to examine clinical differences and
      similarities between liraglutide and these commonly used agents.

PMID- 22405265
TI  - Liraglutide in oral antidiabetic drug combination therapy.
AB  - The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide is indicated as
      an add-on to oral antidiabetic drug regimens in subjects with type 2 diabetes.
      Herein, the results of clinical trials assessing the efficacy, safety and
      tolerability of liraglutide when used in combination with either one or two oral
      antidiabetic therapies are summarised, then contrasted with the effects of
      exenatide and dipeptidyl peptidase (DPP-4) inhibitors. GLP-1 receptor agonists
      lead to effective glycaemic control when used as combination therapy with either
      one or two oral antidiabetic agents, and may confer overall benefits in weight
      loss and blood pressure in some subjects. These agents are well tolerated; the
      most commonly reported adverse effect is mild-to-moderate gastrointestinal
      symptoms, which are usually transient. Rates of hypoglycaemia in these trials
      were low, although higher rates were noted when combined with a sulphonylurea.
      While further study will be required, GLP-1 receptor agonists may offer important
      advantages over other diabetic therapies, including DPP-4 inhibitors.

PMID- 22405266
TI  - Comparison of liraglutide versus other incretin-related anti-hyperglycaemic
      agents.
AB  - The two classes of incretin-related therapies, dipeptidyl peptidase-4 (DPP-4)
      inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have become
      important treatment options for patients with type 2 diabetes. Sitagliptin,
      saxagliptin, vildagliptin and linagliptin, the available DPP-4 inhibitors, are
      oral medications, whereas the GLP-1 RAs-twice-daily exenatide, once-weekly
      exenatide and once-daily liraglutide-are administered subcutaneously. By
      influencing levels of GLP-1 receptor stimulation, these medications lower plasma
      glucose levels in a glucose-dependent manner with low risk of hypoglycaemia,
      affecting postprandial plasma glucose more than most other anti-hyperglycaemic
      medications. Use of GLP-1 RAs has been shown to result in greater glycaemic
      improvements than DPP-4 inhibitors, probably because of higher levels of GLP-1
      receptor activation. GLP-1 RAs can also produce significant weight loss and may
      reduce blood pressure and have beneficial effects on other cardiovascular risk
      factors. Although both classes are well tolerated, DPP-4 inhibitors may be
      associated with infections and headaches, whereas GLP-1 RAs are often associated
      with gastrointestinal disorders, primarily nausea. Pancreatitis has been reported
      with both DPP-4 inhibitors and GLP-1 RAs, but a causal relationship between use
      of incretin-based therapies and pancreatitis has not been established. In
      clinical trials, liraglutide has shown efficacy and tolerability and resulted in
      certain significant benefits when compared with exenatide and sitagliptin.

PMID- 22405267
TI  - Liraglutide: from clinical trials to clinical practice.
AB  - Liraglutide, a once-daily glucagon-like peptide-1 receptor agonist, is approved
      for use as monotherapy in the USA and Japan (but not in Europe or Canada) and in
      combination with selected oral agents (all regions) for the treatment of patients
      with type 2 diabetes. Guidance from local advisory bodies is emerging on the most
      appropriate place for liraglutide in the treatment pathway. It is apparent from
      its phase 3 clinical trial programme that liraglutide provides superior glycaemic
      control compared with that achieved with other antidiabetic agents used early in
      the treatment pathway (e.g. glimepiride and sitagliptin). Key additional benefits
      include a low incidence of hypoglycaemia and clinically relevant weight loss,
      although these benefits may be ameliorated by concomitant sulphonylurea (SU)
      treatment and, in the case of hypoglycaemia, reduction of the SU dose may be
      necessary. Overall, the profile of liraglutide is similar and, in some aspects,
      superior to twice-daily exenatide. The implementation of liraglutide therapy is
      straightforward, with simple dose titration from the starting dose of 0.6 to 1.2
      mg/day after 1 week; some patients may benefit from additional titration to 1.8
      mg/day. Treatment is self-administered by subcutaneous injection. This contrasts
      with other agents used early in the treatment pathway, but clinical data suggest
      patients' overall treatment satisfaction with liraglutide is similar (1.2 mg) or
      better (1.8 mg) than that with sitagliptin despite differing administration
      methods. Some patients may experience nausea when initiating liraglutide
      treatment, but the titration regimen is designed to improve tolerability and
      clinical data indicate nausea is transient.

PMID- 22405268
TI  - Non-glycaemic effects mediated via GLP-1 receptor agonists and the potential for
      exploiting these for therapeutic benefit: focus on liraglutide.
AB  - The glucagon-like peptide-1 receptor agonists (GLP-1 RAs) liraglutide and
      exenatide can improve glycaemic control by stimulating insulin release through
      pancreatic beta-cells in a glucose-dependent manner. GLP-1 receptors are not
      restricted to the pancreas; therefore, GLP-1 RAs cause additional non-glycaemic
      effects. Preclinical and clinical trial data suggest a multitude of additional
      beneficial effects related to GLP-1 RA therapy, including improvements in beta
      cell function, systolic blood pressure and body weight. These effects are of a
      particular advantage to patients with type 2 diabetes, as most are affected by
      beta-cell dysfunction, obesity and hypertension. Transient gastrointestinal
      adverse events, such as nausea and diarrhoea, are also common. To improve
      gastrointestinal tolerability, an incremental dosing approach is used with
      liraglutide and exenatide twice daily. A potential protective role for GLP-1 RAs
      in the cardiovascular and central nervous systems has been suggested from animal
      studies and short-term clinical trials. These effects and other safety aspects of
      GLP-1 therapy are currently being investigated in ongoing long-term clinical
      studies.

PMID- 22405270
TI  - WTX: an unexpected regulator for p53.
AB  - The WTX gene is frequently lost or mutated in Wilms tumor. In this issue of
      Molecular Cell, Kim et al. (2012) identify WTX modulation of p53 tumor-suppressor
      activity through regulation of p53 acetylation. Therefore, WTX differentially
      regulates the oncogenic beta-catenin pathway and the tumor-suppressing p53
      pathway.

PMID- 22405271
TI  - PKM2 enters the morpheein academy.
AB  - In this issue of Molecular Cell, Gao et al. (2012) show that the glycolytic
      enzyme PKM2, in its dimeric form, possesses protein kinase activity and
      phosphorylates STAT3 in the nucleus, thereby driving expression of genes that
      promote transformation.

PMID- 22405272
TI  - Keeping it together in times of stress: checkpoint function at stalled
      replication forks.
AB  - In this issue of Molecular Cell, De Piccoli et al. (2012) show that, contrary to
      current models of DNA replication checkpoint function, replication proteins
      remain associated with each other and with replicating DNA when replication is
      stressed in checkpoint-deficient cells.

PMID- 22405273
TI  - Mechanistic insight into the microtubule and actin cytoskeleton coupling through
      dynein-dependent RhoGEF inhibition.
AB  - Actin-based stress fiber formation is coupled to microtubule depolymerization
      through the local activation of RhoA. While the RhoGEF Lfc has been implicated in
      this cytoskeleton coupling process, it has remained elusive how Lfc is recruited
      to microtubules and how microtubule recruitment moderates Lfc activity. Here, we
      demonstrate that the dynein light chain protein Tctex-1 is required for
      localization of Lfc to microtubules. Lfc residues 139-161 interact with Tctex-1
      at a site distinct from the cleft that binds dynein intermediate chain. An NMR
      based GEF assay revealed that interaction with Tctex-1 represses Lfc nucleotide
      exchange activity in an indirect manner that requires both polymerized
      microtubules and phosphorylation of S885 by PKA. We show that inhibition of Lfc
      by Tctex-1 is dynein dependent. These studies demonstrate a pivotal role of Tctex
      1 as a negative regulator of actin filament organization through its control of
      Lfc in the crosstalk between microtubule and actin cytoskeletons.

PMID- 22405274
TI  - Tex14, a Plk1-regulated protein, is required for kinetochore-microtubule
      attachment and regulation of the spindle assembly checkpoint.
AB  - Proper assembly of kinetochores (KTs) during mitosis is required for bipolar
      attachment of spindle microtubules (MTs) and the accumulation of spindle assembly
      checkpoint (SAC) components. Here we show that testis-expressed protein 14
      (Tex14), which has been implicated in midbody function, is recruited to KTs by
      Plk1 in a Cdk1-dependent manner during early mitosis. Exclusion of Tex14 from
      kinetochores results in an inability to efficiently localize outer KT components,
      impaired KT-MT attachment, chromosome congression defects, and whole-chromosome
      instability. In addition, we demonstrate that phosphorylation of Tex14 by Plk1
      during metaphase promotes APC(Cdc20)-mediated Tex14 degradation. Inhibition of
      this phosphorylation event causes retention of Tex14 at KTs and results in
      delayed metaphase-to-anaphase transition and chromosome segregation defects. Our
      findings identify Tex14 as an important mediator of KT structure and function and
      the fidelity of chromosome separation.

PMID- 22405275
TI  - To the young investigator.

PMID- 22405276
TI  - Statistical analysis plan for the third International Stroke Trial (IST-3); part
      of a 'thread' of reports of the trial.

PMID- 22405277
TI  - An outcomes approach to stroke care: the importance of teamwork and evidence
      based nursing care.
AB  - The Quality in Acute Stroke Care (QASC) was a cluster randomised control trial
      (CRCT) which evaluated the effectiveness of evidence-based clinical treatment
      protocols for the management of fever, hyperglycaemia and swallowing, in
      conjunction with multidisciplinary team building workshops, and a standardised
      interactive staff education program (collectively known as the Fever, Sugar,
      Swallowing (FeSS) intervention) to improve patient outcomes 90-days. We found
      that patients cared for in stroke units who received our intervention were 15.7%
      more likely to be alive and independent 90 days following their stroke. They also
      had significantly: fewer episodes of fever, lower mean temperatures, lower mean
      blood glucose levels, and better screening for swallowing difficulties.

PMID- 22405278
TI  - Assessment of additional endpoints for trials in acute stroke - what, when,
      where, in who?
AB  - Functional outcome in acute stroke trials among others is usually measured on the
      modified Rankin Scale. However, new onset of depression, cognitive decline, and
      communication deficits alone or in combination affect more than 25% of patients.
      This report summarizes the findings and conclusions of a workshop by the European
      Stroke Organization held in February 2011 We propose that assessment of mood
      disorders, cognitive impairment/dementia, language or communication dysfunction,
      and quality of life should supplement outcome measures after acute stroke.

PMID- 22405279
TI  - The effectiveness of secondary prevention lifestyle interventions designed to
      change lifestyle behavior following stroke: summary of a systematic review.
AB  - BACKGROUND: A feature of stroke is that it recurs (25% within five-years). Risk
      factors for stroke and recurrent stroke include smoking, alcohol consumption,
      poor diet, and physical inactivity. AIM: To evaluate the effectiveness of
      secondary prevention lifestyle interventions designed to change lifestyle
      behavior following stroke. This short paper presents a summary of the systematic
      review process and findings. METHODS: Ten major databases were searched using
      subject headings and key words. Papers were screened using review-specific
      criteria. Critical appraisal and data extraction were conducted independently by
      two reviewers. Data were pooled in statistical meta-analysis; where this was not
      possible findings were presented in narrative form. RESULTS: Three studies
      involving 581 participants were reviewed. Two models of intervention delivery
      were reported: shared care and nurse-led. Interventions were delivered to groups
      or in one-to-one consultations. Metaanalyses of the pooled lifestyle data favored
      the interventions (2P = 0.02). In terms of physiological outcomes, while overall
      treatment effect was not significant, pooled results did approach statistical
      significance (2P = 0.08), however the test of heterogeneity was significant,
      suggesting differences in the variables that were pooled. Pooled secondary
      outcomes, including perceived health status and stroke knowledge, favored the
      interventions (2P < 0.00001), however, the test for heterogeneity was highly
      significant. CONCLUSION: Stroke secondary prevention lifestyle interventions are
      effective in terms of effecting positive change in lifestyle behaviors and
      secondary outcomes, and appear promising in relation to physiological outcomes.
      There was insufficient evidence to determine the effect of intervention on
      incidence of stroke recurrence.

PMID- 22405280
TI  - Stroke burden in adults in Armenia.
AB  - We investigated around 100 patients for one-year and then registered the
      information about the possible etiology of the stroke, type of disease,
      treatment, localization of the clot, age, as well as gender distribution of
      stroke patients' population. This general overview of risk factors, ways of
      treatment, diagnostics, care and monitoring of the stroke patients in Armenia
      might serve as a cornerstone work for further highlighting of new avenues for
      stroke treatment.

PMID- 22405281
TI  - CVST, distinguished from nonthrombotic CVSS before treatment - a MUST.

PMID- 22405282
TI  - Procoagulant and prothrombotic effects of the herbal medicine, Dipsacus asper and
      its active ingredient, dipsacus saponin C, on human platelets.
AB  - BACKGROUND: In spite of the growing popularity of herbal medicines and natural
      food supplements, their effects on cardiovascular homeostasis remain largely
      unknown, especially regarding pro-thrombotic risks. OBJECTIVE: In the present
      study, 21 herbal tea extracts were screened for the procoagulant activities on
      platelets, an important promoter of thrombosis to examine if herbal medicines or
      natural products may have prothrombotic risks. We discovered that Dipsacus asper
      (DA), known to have analgesic and anti-inflammatory effects, potently induced
      procoagulant activities in platelets. We tried to identify the active ingredient
      and elucidate the underlying mechanism. RESULTS: Among 10 major ingredients of
      DA, dipsacus saponin C (DSC) was identified as a key active ingredient in DA
      induced procoagulant activities. DSC-induced procoagulant activities were
      achieved by the exposure of phosphatidylserine (PS) and PS-bearing microparticle
      generation that were caused by the alteration in the activities of phospholipid
      translocases: scramblase and flippase. These events were initiated by increased
      intracellular calcium and ATP depletion. Notably, DSC induced a series of
      apoptotic events including the disruption of mitochondrial membrane potential,
      translocation of Bax and Bak, cytochrome c release and caspase-3 activation. The
      key roles of apoptotic pathway and caspase activation were demonstrated by the
      reversal of DSC-induced PS exposure and procoagulant activities with the
      pretreatment of caspase inhibitors. Interestingly, EGTA reversed DSC-induced
      procoagulant activities and apoptotic events suggesting that an intracellular
      calcium increase may play a central role. These results were also confirmed in
      vivo where platelets of the rats exposed to DSC or DA exhibited PS exposure. Most
      importantly, DSC or DA administration led to increased thrombus formation.
      CONCLUSION: These results demonstrate that herbal medicines or natural products
      such as DA or DSC might have prothrombotic risks through procoagulant activation
      of platelets.

PMID- 22405283
TI  - Applications of functionalized and nanoparticle-modified nanocrystalline
      cellulose.
AB  - Nanocrystalline cellulose (NCC), a rod-shaped nanoscale material with exceptional
      strength and physicochemical properties, can be prepared from inexpensive
      renewable biomass. Besides its potential use as a reinforcing agent for
      industrial biocomposites, pristine NCC exhibits low toxicity and poses no serious
      environmental concerns, providing impetus for its use in bioapplications. Here,
      we review recent developments in the use of modified NCC for emerging
      bioapplications, specifically enzyme immobilization, antimicrobial and medical
      materials, green catalysis, biosensing and controlled drug delivery. We focus on
      the modification of NCC with chemical functionalities and inorganic
      nanoparticles, reviewing practical considerations such as reusability, toxicity
      and scale-up capability.

PMID- 22405284
TI  - Metal-ligand interactions: an analysis of zinc binding groups using the Protein
      Data Bank.
AB  - In the present study, we investigated zinc binding groups (ZBGs) using the
      coordinates of protein-ligand complex structures obtained from the Protein Data
      Bank. The distance from the zinc to the nearest ligand atom was measured to
      determine whether the atom was part of the ZBG. The most frequently found ZBG was
      carboxylate, followed by sulfonamide, hydroxamate, and phosphonate/phosphate.
      Because it was found that few heteroatoms, such as nitrogen, oxygen, and sulfur
      atoms, interacted with zinc, ideal distances between the zinc and these
      heteroatoms were identified. Whereas carboxylates bound to the zinc via both
      monodentate and bidentate interactions, the hydroxamates bound dominantly in a
      bidentate manner. These results will aid in the design of new inhibitors with the
      potential to interact with zinc in the target protein.

PMID- 22405286
TI  - Recent advances in the synthesis of raloxifene: a selective estrogen receptor
      modulator.
AB  - Estrogens are a group of steroids that exert important effects on reproductive
      and many non-reproductive tissues. Selective estrogen receptor modulators (SERM)
      are a class of therapeutic agents widely prescribed for the treatment and
      prevention of breast cancer, osteoporosis, and postmenopausal symptoms.
      Raloxifene, an example of oral SERM is prescribed primarily for the treatment and
      prevention of postmenopausal disorders in woman. The current review provides an
      outline of practical methodologies used to access benzothiophenyl scaffolds of
      raloxifene and relevant structural analogs. The contents are discussed in five
      sections: (a) synthesis of raloxifene, (b) organometallic analogs, (c)
      radiolabelled analogs, (d) constrained raloxifene analogs, and (e) other oxygen,
      sulfur, and nitrogen based raloxifene analogs. In addition to the synthesis,
      biological activity of a few synthetic analogs has been discussed.

PMID- 22405285
TI  - Synthesis of novel spirooxindole derivatives by one pot multicomponent reaction
      and their antimicrobial activity.
AB  - A series of novel spirooxindoles have been synthesized through 1,3-dipolar
      cycloaddition of an azomethine ylide generated from isatin and sarcosine or l
      proline with the dipolarophile 1,4-naphthoquinone followed by spontaneous
      dehydrogenation. Synthesised compounds were evaluated for their antimicrobial
      activities against eight bacteria and three fungi. All the spirooxindole
      derivatives exhibited significant antibacterial activity against Staphylococcus
      aureus, S. aureus (MRSA), Enterobacter aerogens, Micrococcus luteus, Proteus
      vulgaris, Klebsiella pneumonia, Salmonella typhimurium, Salmonella paratyphi-B
      and anti-fungal activity against Malassesia pachydermatis, Candida albicans and
      Botyritis cinerea organisms. Among 23 compounds screened, 1'-acetyl-2,5'-dimethyl
      2,3-dihydrospiro[benzo[f]isoindole-1,3'-indoline]-2',4,9-trione was found to be
      more active against tested bacteria and fungi.

PMID- 22405287
TI  - Facile synthesis, characterization and pharmacological activities of 3,6
      disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles and 5,6-dihydro-3,6
      disubstituted-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles.
AB  - Two new series of compounds namely, 3,6-disubstituted-1,2,4-triazolo[3,4
      b][1,3,4]thiadizoles (5a-j) and 5,6-dihydro-3,6-disubstituted-1,2,4-triazolo[3,4
      b][1,3,4]thiadizoles (7a-j) were prepared. In continuation of a previously
      reported study, the first series (5a-j) were synthesized by the cyclocondensation
      of 4-amino-5-(2-bromo-5-methoxyphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (4)
      with various substituted aromatic carboxylic acids in phosphorus oxychloride and
      the second series (7a-j) by the reaction of (4) with various substituted aromatic
      aldehydes in the presence of p-Toluene sulfonic acid. Reaction of (4) with the
      aldehyde (9) afforded the Schiff's base (10) and not the cyclised product (11) on
      treatment with p-Toluene sulfonic acid. Synthesized compounds were structurally
      confirmed by spectral analysis and studied for their anti-inflammatory,
      analgesic, anti-oxidant and antimicrobial activities. Some of the tested
      compounds showed significant pharmacological activities.

PMID- 22405288
TI  - Synthesis and biological evaluation of piperidine-substituted triazine
      derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors.
AB  - A novel series of piperidine-substituted triazine derivatives have been
      synthesized and evaluated for anti-HIV activities in MT-4 cells. Most compounds
      displayed extremely promising activity against wild-type HIV-1 with EC(50) values
      in low nanomolar concentration, better than that of Nevirapine, Delavirdine,
      Zidovudine and Dideoxycitidine, and higher potency towards the resistant mutant
      strain K103N/Y181C than that of Nevirapine and Delavirdine. Selected compounds
      were also assayed against reverse transcriptase with lower IC(50) values than
      that of Nevirapine. The structure-activity relationship (SAR) of these novel
      structural congeners was also discussed.

PMID- 22405289
TI  - Thieno[2,3-d]pyrimidinedione derivatives as antibacterial agents.
AB  - Several thieno[2,3-d]pyrimidinediones have been synthesized and examined for
      antibacterial activity against a range of gram-positive and gram-negative
      pathogens. Two compounds displayed potent activity (2-16 mg/L) against multi-drug
      resistant gram-positive organisms, including methicillin resistant, vancomycin
      intermediate, vancomycin-resistant Staphylococcus aureus (MRSA, VISA, VRSA) and
      vancomycin-resistant enterococci (VRE). Only one of these agents possessed
      moderate activity (16-32 mg/L) against gram-negative strains. An examination of
      the cytotoxicity of these agents revealed that they displayed low toxicity (40-50
      mg/L) against mammalian cells and very low hemolytic activity (2-7%). Taken
      together, these studies suggest that thieno[2,3-d]pyrimidinediones are
      interesting scaffolds for the development of novel gram-positive antibacterial
      agents.

PMID- 22405290
TI  - Novel NSAID 1-acyl-4-cycloalkyl/arylsemicarbazides and 1-acyl-5-benzyloxy/hydroxy
      carbamoylcarbazides as potential anticancer agents and antioxidants.
AB  - The novel 1-acyl-4-cycloalkyl/arylsemicarbazides (5a-y) and 1-acyl-5
      benzyloxy/hydroxycarbamoylcarbazides (8a-f) derived from the nonsteroidal anti
      inflammatory drugs ibuprofen, fenoprofen and reduced ketoprofen were prepared,
      fully chemically characterized and evaluated for their cytostatic, antiviral and
      antioxidant activities. Compounds 5 and 8 consist of a region rich in
      electronegative atoms (five to nine nitrogen and oxygen atoms) framed by aryl or
      cycloalkyl residues on one or both terminal ends. The synthetic pathways applied
      for the preparation of the title compounds involved a benzotriazole as a
      synthetic auxiliary in several steps. Three of the tested compounds, namely 4
      benzhydryl-1-[2-(3-phenoxyphenyl)propanoyl]semicarbazide (5l), 4-benzhydryl-1-[2
      (3-benzylphenyl)propanoyl]semicarbazide (5s), and 4-benzhydryl-1-[2-(4
      isobutylphenyl)propanoyl]semicarbazide (5f) showed pronounced antiproliferative
      activity in vitro against six cancer cell lines (IC(50)=3-23 MUM). The same
      compounds highly inhibited soybean lipoxygenase (IC(50)=60 and 51.5 MUM) and
      lipid peroxidation as well (99, 88 and 74%, respectively). 4-Benzyloxy-1-[2-(4
      isobutylphenyl)propanoyl]semicarbazide (5t) and 5-benzyloxycarbamoyl-1-[2-(3
      benzylphenyl)propanoyl]carbazide (8c) exerted complete lipid peroxidation
      inhibition. Semicarbazides 5w-y and carbazides 8d-f bearing a hydroxamic
      acid/hydroxyurea moiety showed a modest antiradical activity in DPPH test, while
      the best radical scavenger was 1-(1-benzotriazolecarbonyl)-4
      benzyloxysemicarbazide (7). None of the compounds were inhibitory to a broad
      panel of DNA and RNA viruses in the cell culture at subtoxic concentrations.

PMID- 22405291
TI  - Synthesis and evaluation of CS-2100, a potent, orally active and S1P(3)- sparing
      S1P(1) agonist.
AB  - Modulators of sphingosine phosphate receptor-1 (S1P(1)) have recently been
      focused as a suppressant of autoimmunity. We have discovered a 4-ethylthiophene
      based S1P(1) agonist 1-({4-Ethyl-5-[5-(4-phenoxyphenyl)-1,2,4-oxadiazol-3-yl]-2
      thienyl}methyl)azetidine-3-carboxylic acid (CS-2100, 8) showing potent S1P(1)
      agonist activity against S1P(3) and an excellent in vivo potency. We report
      herein the synthesis of CS-2100 (8) and pharmacological effects such as S1P(1)
      and S1P(3) agonist activity in vitro, peripheral blood lymphocyte lowering
      effects and the suppressive effects on adjuvant-induced arthritis and
      experimental autoimmune encephalomyelitis (EAE) in animal models. The
      pharmacokinetic data were also reported. CS-2100 (8) had >5000-fold greater
      agonist activity for human S1P(1) (EC(50); 4.0 nM) relative to S1P(3) (EC(50);
      >20,000 nM). Following administration of single oral doses of 0.1 and 1 mg/kg of
      CS-2100 (8) in rats, lymphocyte counts decreased significantly, with a nadir at 8
      and/or 12 h post-dose and recovery to vehicle control levels by 24-48 h post
      dose. CS-2100 (8) is efficacious in the adjuvant-induced arthritis model in rats
      (ID(50); 0.44 mg/kg). In the EAE model compared to the vehicle-treated group,
      significant decreases in the cumulative EAE scores were observed for 0.3 and 1
      mg/kg CS-2100 (8) groups in mice. While CS-2100 (8) showed potent efficacy in
      various animal disease models, it was also revealed that the central 1,2,4
      oxadiazole ring of CS-2100 (8) was decomposed by enterobacteria in intestine of
      rats and monkeys, implicating the latent concern about an external susceptibility
      in its metabolic process in the upcoming clinical studies.

PMID- 22405292
TI  - Insights from magnetic resonance imaging of left ventricular non-compaction in
      adults of North African descent.
AB  - BACKGROUND: Left ventricular non-compaction (LVNC) is a recently recognized rare
      disorder. Magnetic resonance imaging (MRI) may help to clarify the uncertainties
      related to this genetic cardiomyopathy. Despite the fact that many articles have
      been published concerning the use of MRI in the study of LVNC, there is a lack of
      data describing the disease in the North African population. The aim of our study
      is to clarify MRI findings of LVNC in North African patients. METHODS: In our
      retrospective cohort, twelve patients (7 male, mean age 53 +/- 8 years) underwent
      MRI for suspected LVNC. Correlations were investigated between the number of non
      compacted segments per patient and left ventricular ejection fraction (LVEF),
      then between the number of non-compacted segments and left ventricular end
      diastolic diameter. The presence or absence of late gadolinium enhancement (LGE)
      was qualitatively determined for each left ventricular myocardial segment.
      RESULTS: Non-compaction was more commonly observed at the apex, the anterior and
      the lateral walls, especially on their apical and mid-cavity segments. 83% of
      patients had impaired LVEF. There was no correlation between the number of non
      compacted segments per patient and LVEF (r = -0.361; p = 0.263), nor between the
      number of non-compacted segments per patient and left ventricular end diastolic
      diameter (r = 0.280; p = 0.377). LGE was observed in 22 left ventricular
      segments. No association was found between the pattern of fibrosis and non
      compaction distribution (OR = 2.2, CI [0.91-5.55], p = 0.076). CONCLUSION: The
      distribution of LVNC in North African patients does not differ from other
      populations. Ventricular dysfunction is independent from the number of non
      compacted segments. Myocardial fibrosis is not limited to non-compacted areas but
      can extend to compacted segments.

PMID- 22405293
TI  - Identification and characterization of a novel Neospora caninum immune mapped
      protein 1.
AB  - Immune mapped protein 1 (IMP1) is a newly discovered protein in Eimeria maxima.
      It is recognized as a potential vaccine candidate against E. maxima and a highly
      conserved protein in apicomplexan parasites. Although the Neospora caninum IMP1
      (NcIMP1) orthologue of E. maxima IMP1 was predicted in the N. caninum genome, it
      was still not identified and characterized. In this study, cDNA sequence encoding
      NcIMP1 was cloned by RT-PCR from RNA isolated from Nc1 tachyzoites. NcIMP1 was
      encoded by an open reading frame of 1182 bp, which encoded a protein of 393 amino
      acids with a predicted molecular weight of 42.9 kDa. Sequence analysis showed
      that there was neither a signal peptide nor a transmembrane region present in the
      NcIMP1 amino acid sequence. However, several kinds of functional protein motifs,
      including an N-myristoylation site and a palmitoylation site were predicted.
      Recombinant NcIMP1 (rNcIMP1) was expressed in Escherichia coli and then purified
      rNcIMP1 was used to prepare specific antisera in mice. Mouse polyclonal
      antibodies raised against the rNcIMP1 recognized an approximate 43 kDa native
      IMP1 protein. Immunofluorescence analysis showed that NcIMP1 was localized on the
      membrane of N. caninum tachyzoites. The N-myristoylation site and the
      palmitoylation site were found to contribute to the localization of NcIMP1.
      Furthermore, the rNcIMP1-specific antibodies could inhibit cell invasion by N.
      caninum tachyzoites in vitro. All the results indicate that NcIMP1 is likely to
      be a membrane protein of N. caninum and may be involved in parasite invasion.

PMID- 22405294
TI  - Electrochemical stripping analysis of nanogold label-induced silver deposition
      for ultrasensitive multiplexed detection of tumor markers.
AB  - A multiplexed electrochemical immunoassay method was developed for simultaneous
      ultrasensitive measurement of tumor markers based on electrochemical stripping
      analysis of silver nanoparticles (Ag NPs). The Ag NPs were deposited on a
      disposable immunosensor array with a reduction reaction catalyzed by nanogold
      labels. The immunosensor array was prepared by covalently immobilizing capture
      antibodies on chitosan modified screen-printed carbon electrodes. Through a
      sandwich-type immunoreaction, antibody-functionalized Au NPs were captured onto
      immunosensor surface to induce the silver deposition from a silver enhancer
      solution. The deposited Ag NPs could be directly measured by anodic stripping
      analysis in KCl solution. The catalytic deposition enhanced the analytical
      sensitivity for detection of protein markers. The interference of dissolved
      oxygen could be avoided as the detection was performed with positive stripping
      potential range. Using carcinoembryonic antigen and alpha-fetoprotein as model
      analytes, the proposed multiplexed immunoassay method showed wide linear ranges
      of three orders of magnitude with the detection limits down to 3.5 and 3.9 pg mL(
      1), respectively. The localized silver deposition, as well as the stripping
      detection process, eliminated completely the electrochemical cross talk between
      adjacent immunosensors. The immunosensor array exhibited acceptable
      reproducibility, stability and accuracy, showing a promising potential in
      multianalyte determination for clinical application.

PMID- 22405295
TI  - Probing protein interactions with hydrogen/deuterium exchange and mass
      spectrometry-a review.
AB  - Assessing the functional outcome of protein interactions in structural terms is a
      goal of structural biology, however most techniques have a limited capacity for
      making structure-function determinations with both high resolution and high
      throughput. Mass spectrometry can be applied as a reader of protein chemistries
      in order to fill this void, and enable methodologies whereby protein structure
      function determinations may be made on a proteome-wide level. Protein
      hydrogen/deuterium exchange (H/DX) offers a chemical labeling strategy suitable
      for tracking changes in "dynamic topography" and thus represents a powerful means
      of monitoring protein structure-function relationships. This review presents the
      exchange method in the context of interaction analysis. Applications involving
      interface detection, quantitation of binding, and conformational responses to
      ligation are discussed, and commentary on recent analytical developments is
      provided.

PMID- 22405296
TI  - Speciation of mercury in fish samples by flow injection catalytic cold vapour
      atomic absorption spectrometry.
AB  - A rapid flow injection catalytic cold vapour atomic absorption spectrometric (FI
      CCV-AAS) method is described for speciation and determination of mercury in
      biological samples. Varying concentrations of NaBH(4) were employed for mercury
      vapour generation from inorganic and mixture of inorganic and organic (total) Hg.
      The presence of Fe(3+), Cu(2+) and thiourea had catalytic effect on mercury
      vapour generation from methylmercury (MeHg) and, when together, Cu(2+) and
      thiourea had synergistic catalytic effect on the vapour generation. Of the two
      metal ions, Fe(3+) gave the best sensitivity enhancement, achieving the same
      sensitivity for MeHg and inorganic Hg(2+). Due to similarity of resulting
      sensitivity, Hg(2+) was used successfully as a primary standard for
      quantification of inorganic and total Hg. The catalysis was homogeneous in
      nature, and it was assumed that the breaking of the C-Hg bond was facilitated by
      the delocalization of the 5d electron pairs in Hg atom. The extraction of MeHg
      and inorganic mercury (In-Hg) in fish samples were achieved quantitatively with
      hydrochloric acid in the presence of thiourea and determined by FI-CCV-AAS. The
      application of the method to the quantification of mercury species in a fish
      liver reference material DOLT-4 gave 91.5% and 102.3% recoveries for total and
      methyl mercury, respectively. The use of flow injection enabled rapid analysis
      with a sample throughput of 180 h(-1).

PMID- 22405297
TI  - A new formulation to estimate the variance of model prediction. Application to
      near infrared spectroscopy calibration.
AB  - Evaluation of uncertainty affecting predictions is a major trend in analytical
      chemistry and chemometrics. Several approximate expressions and resampling
      methods have been proposed for the estimation of prediction uncertainty when
      using multivariate calibration. This article proposes a new expression for the
      variance of prediction, adapted to near infrared spectroscopy specificities and
      particularly to the spectral error structure, induced by the high colinearity of
      the variables. The proposed analytical expression enables a detailed evaluation
      of the different contributions and components of uncertainty affecting the model.
      An application to real data of feedstuff near infrared spectra related to protein
      content has shown its advantages.

PMID- 22405298
TI  - Potential antioxidant compounds in Mallotus species fingerprints. Part II:
      fingerprint alignment, data analysis and peak identification.
AB  - Some Mallotus species are commonly used as traditional medicine (TM) ingredients
      in Vietnam and China, but only a few are studied for their activities. In Part I,
      high-performance liquid chromatography (HPLC) fingerprints of 39 Mallotus samples
      (17 species) were developed and, because of the complexity of and the large
      differences between the samples, it was chosen to analyse the unaligned
      fingerprints. The peaks, potentially responsible for the antioxidant activity in
      given Mallotus species, were indicated by the regression coefficients from an
      orthogonal projections to latent structures (O-PLS) model. In the present study,
      an in depth discussion on the need for alignment of the Mallotus fingerprints for
      the indication of the potentially active compounds is made, as well as an
      experimental analysis and identification of the previously indicated peaks by
      HPLC-mass spectrometry (HPLC-MS). Additionally, to thoroughly study and discuss
      the alignment problem, the modelling and prediction of the antioxidant activity
      of green tea samples based on HPLC fingerprints were also considered.

PMID- 22405299
TI  - Fractions of Rechtschaffner matrices as supersaturated designs in screening
      experiments aimed at evaluating main and two-factor interaction effects.
AB  - Optimal fractions of resolution V design matrices proposed by Rechtschaffner in
      1967 are developed and applied as supersaturated designs in screening
      experiments. Rechtschaffner matrices allow evaluation of all main factors and two
      factor interactions, which in many real-world studies are of practical
      significance. However, the number of experimental runs increases rapidly with the
      number of factors in the matrices, which are therefore impractical for more than
      5-6 factors. On the contrary, saturated fractions based on Hadamard matrices,
      which are commonly applied in screening studies, cannot evaluate the interaction
      effects. Here, a procedure for selecting the optimum fractions of Rechtschaffner
      matrices is presented and provides supersaturated matrices that are well adapted
      to a variety of problems, thus allowing the development of screening studies with
      a relatively small number of experiments. The procedures developed to derive the
      size-reduced matrices and to evaluate the active factors are discussed and
      compared in terms of efficiency and reliability, by means of simulation studies
      and application to a real problem. These fractions are the first supersaturated
      design matrices capable of estimating interaction effects. Additionally, one
      important advantage of these supersaturated matrices is that they enable
      development of follow-up procedures in cases of inconclusive results, by
      enlarging the matrix and eventually resolving the full Rechtschaffner matrix of
      departure when it is necessary to evaluate the active factors and their
      interactions.

PMID- 22405300
TI  - Simultaneous electrochemical sensing of ascorbic acid, dopamine and uric acid at
      anodized nanocrystalline graphite-like pyrolytic carbon film electrode.
AB  - Nanocrystalline graphite-like pyrolytic carbon film (PCF) electrode fabricated by
      a non-catalytic chemical vapor deposition (CVD) process was used for the
      simultaneous electrochemical sensing of ascorbic acid (AA), dopamine (DA), and
      uric acid (UA). The electrode was studied with respect to changes in
      electrocatalytic activity caused by a simple and fast electrochemical
      pretreatment. The anodized electrode exhibited excellent performance compared to
      many chemically modified electrodes in terms of detection limit, linear dynamic
      range, and sensitivity. Differential pulse voltammetry (DPV) was used for the
      simultaneous determination of ternary mixtures of DA, AA, and UA. Under optimum
      conditions, the detection limits were 2.9 MUM for AA, 0.04 MUM for DA, and 0.03
      MUM for UA with sensitivities of 0.078, 5.345, and 6.192 A M(-1), respectively.
      The peak separation was 219 mV between AA and DA and 150 mV between DA and UA. No
      electrode fouling was observed and good reproducibility was obtained in all the
      experiments. The sensor was successfully applied for the assay of DA in an
      injectable drug and UA in human urine by using standard addition method.

PMID- 22405301
TI  - Microporous silica with nanolayer structure coated with renewable organic solvent
      film as a novel extracting phase: a combination of solid- and liquid-phase
      microextraction.
AB  - A new method based on combination of solid- and liquid-phase microextraction was
      developed. For the first time, porous flower-like silica microstructures with
      nanometric layers were created on the surface of the stainless steel wire by a
      new facile hydrothermal process. The fiber, coated with a suitable organic
      solvent, was applied for microextraction of some organophosphorus pesticides from
      aqueous samples followed by gas chromatography-nitrogen phosphorous detection.
      Method detection limits were between 0.6 and 3 ng L(-1). Relative standard
      deviations for intra- and inter-day precision were 4.4-7.3% and 5.1-7.8%,
      respectively. Fiber-to-fiber reproducibility for five prepared fibers was 6.3
      8.4%. Tap, river and waste water samples were analyzed for evaluation of the
      method in real sample analysis. Relative recoveries for spiked tap, river and
      waste water samples were in the range of 94-101%, 89-97% and 82-103%,
      respectively. In addition, the method was compared with two commercial solid
      phase microextraction (SPME) fibers, single drop microextraction (SDME) and
      liquid-phase microextraction (LPME). The present method showed higher extraction
      efficiency as compared with SDME, LPME and commercial SPME fibers.

PMID- 22405302
TI  - Preparation, evaluation and characterization of quercetin-molecularly imprinted
      polymer for preconcentration and clean-up of catechins.
AB  - Molecularly imprinted polymer (MIP) for solid extraction and preconcentration of
      catechins have been successfully prepared by a thermal polymerization method
      using quercetin as template, 4-vinylpyridine as functional monomer and ethylene
      glycol dimethacrylate as crosslinker. A solution mixture of acetone and
      acetonitrile was used as porogen. Systematic investigations of the influence of
      monomer, cross-linker, porogen, as well as polymerization conditions on the
      properties of the MIPs were carried out. The quercetin MIPs were evaluated
      according to their selective recognition properties for quercetin, structurally
      related compounds (catechin, epigallocatechin gallate and epicatechin) and a
      unrelated compound of similar molecular size (alpha-tocopherol). Good binding was
      observed for quercetin, catechin and epigallocatechin gallate with an optimized
      MIP in a solid phase extraction system. Adsorption and kinetic characteristics
      were evaluated for catechins which indicated that the synthesized polymer had
      high adsorption capacity and contained homogeneous binding sites. Chemical and
      morphological characterization of the MIP was investigated by FTIR, SEM and BET,
      which confirmed a high degree of polymerization. Finally, the MIP was
      successfully applied to the clean-up and preconcentration of catechins from
      several natural samples.

PMID- 22405304
TI  - Highly sensitive polymerase chain reaction-free quantum dot-based quantification
      of forensic genomic DNA.
AB  - Forensic DNA samples can degrade easily due to exposure to light and moisture at
      the crime scene. In addition, the amount of DNA acquired at a criminal site is
      inherently limited. This limited amount of human DNA has to be quantified
      accurately after the process of DNA extraction. The accurately quantified
      extracted genomic DNA is then used as a DNA template in polymerase chain reaction
      (PCR) amplification for short tandem repeat (STR) human identification.
      Accordingly, highly sensitive and human-specific quantification of forensic DNA
      samples is an essential issue in forensic study. In this work, a quantum dot
      (Qdot)-labeled Alu sequence was developed as a probe to simultaneously satisfy
      both the high sensitivity and human genome selectivity for quantification of
      forensic DNA samples. This probe provided PCR-free determination of human genomic
      DNA and had a 2.5-femtogram detection limit due to the strong emission and
      photostability of the Qdot. The Qdot-labeled Alu sequence has been used
      successfully to assess 18 different forensic DNA samples for STR human
      identification.

PMID- 22405303
TI  - Optimization of headspace solid-phase microextraction for analysis of beta
      caryophyllene in a nanoemulsion dosage form prepared with copaiba (Copaifera
      multijuga Hayne) oil.
AB  - Recent studies have shown the anti-inflammatory activity of Copaiba oils may be
      addressed to the high content of beta-caryophyllene, the most common
      sesquiterpene detected, especially in the Copaifera multijuga Hayne species. In
      the present study, nanoemulsions were proposed as a delivery system for copaiba
      oil in view to treat locally inflamed skin. This article describes the
      optimization and validation of a stability-indicating SPME-GC method, for beta
      caryophyllene analysis in the nanoemulsions produced by high pressure
      homogenization. SPME methods are performed with PDMS (polydimethylsiloxane) fiber
      (100 MUm). Three SPME parameters were evaluated by a three-level-three-factor Box
      Behnken factorial design as potentially affecting the technique efficiency.
      According to the results obtained, the best conditions to extract beta
      caryophyllene were: (i) sampling temperature of 45 degrees C, (ii) sampling time
      of 20 min and (iii) no NaCl addition. Results coming from the forced degradation
      tests showed a reduction of beta-caryophyllene peak area when both caryophyllene
      methanolic solution and nanoemulsions were exposed to acid hydrolysis, UV-A
      irradiation, oxidative (H(2)O(2)) and thermolitic (60 degrees C) conditions. Such
      reduction occurred in lower extent in the nanoemulsions, suggesting a protective
      effect of the formulation to beta-caryophyllene content. Since no degradation
      products were detected in the same retention time of beta-caryophyllene, the
      specificity of the method was demonstrated. The method was linear in the range of
      0.14-0.68 MUg mL(-1) of beta-caryophyllene (r(2)>0.999), and was also validated
      for precision (R.S.D.<=5.0%), accuracy (97.85-101.87%) and robustness. Finally,
      the method was applied to quantification of beta-caryophyllene content in the
      developed formulations.

PMID- 22405305
TI  - Fluorimetric detector and sensor for flow analysis made of light emitting diodes.
AB  - Two compact optoelectronic fluorimetric devices operating according to the paired
      emitter-detector-diode concept have been developed. The fluorimetric detector,
      fabricated of three light emitting diodes only, has been applied for the
      development of fluorimetric optosensor by further integration with sensing solid
      phase. In these investigations as a model analyte and as a model sensing layer
      useful for solid phase spectrometry, riboflavin and C18-silica have been chosen,
      respectively. Both developed analytical devices have been applied for non
      stationary fluorimetric measurements performed under conditions of flow injection
      analysis. The presented flow-through detector and sensor operating under given
      flow conditions offer riboflavin determination in mg L(-1) and MUg L(-1) ranges
      of concentration, respectively.

PMID- 22405306
TI  - Exploiting adsorption and desorption at solid-liquid interface for the
      fluorometric monitoring of glibenclamide in adulterated drinks.
AB  - Nowadays, the use of a drug to modify a person's behavior with criminal
      intentions has become a growing public concern. In fact, stealthy drink spiking
      with certain drugs can cause the incapacitation of a potential victim of assault
      and in extreme cases can even lead to death. Belonging to the group of drugs used
      to commit drug-facilitated crimes is glibenclamide, which not only exhibits high
      sedation secondary effects but when subject to an overdose intake can lead to
      intense hypoglycemic episodes that could end with death. Suicide attempts and
      homicides through overdose with glibenclamide have already been reported. In this
      work and for the first time, it was developed a new methodology for detection of
      glibenclamide in spiked liquid samples (teas) by fluorometry (lambda(ex)=300 nm;
      lambda(em)=404 nm). The novel methodology was also implemented in a miniaturized
      and portable automatic flow system based in the concept of multipumping with an
      in-line pre-separation unit. The separation of the drug from the liquid samples
      was achieved through adsorption of the drug into activated charcoal packed within
      a mini column followed by elution with a solution composed by ethanol,
      hydrochloric acid and the surfactant CTAB (70%, 1.0 mol L(-1), 0.01 mol L(-1),
      respectively). The results allowed to obtain a linear working range for
      glibenclamide concentrations of up to 50 mg L(-1) (r=0.9999) and the detection
      limit was about 0.81 mg L(-1) of glibenclamide.

PMID- 22405307
TI  - Analysis of intercellular calcium signaling using microfluidic adjustable laminar
      flow for localized chemical stimulation.
AB  - The propagation of intercellular calcium signals provides a mechanism to
      coordinate cell population activity, which is essential for regulating cell
      behavior and organ development. However, existing analytical methods are
      difficult to realize localized chemical stimulation of a single cell among a
      population of cells that are in close contact with one another for studying the
      propagation of calcium wave. In this work, a microfluidic method is presented for
      the analysis of contact-dependent propagation of intercellular calcium wave
      induced by extracellular ATP using multiple laminar flows. Adjacent cells were
      seeded ~300 MUm downstream the intersection of a Y-shaped microchannel with
      negative pressure pulses. Consequently, the lateral diffusion distance of the
      chemical at cell locations was limited to ~26 MUm with a total flow rate of 20
      MUL min(-1), which prevented the interference of diffusion-induced cellular
      responses. Localized stimulation of the target cell with ATP induced the
      propagation of intercellular calcium wave among the cell population. In addition,
      studies on the spread of intercellular calcium wave under octanol inhibition
      allowed us to characterize the gap junction mediated cell-cell communication.
      Thus, this novel device will provide a versatile platform for intercellular
      signal transduction studies and high throughput drug screening.

PMID- 22405308
TI  - Development of a candidate certified reference material of cypermethrin in green
      tea.
AB  - This paper presents the preparation of a candidate certified reference material
      (CRM) of cypermethrin in green tea, GLHK-11-01a according to the requirements of
      ISO Guide 34 and 35. Certification of the material was performed using a newly
      developed isotope dilution mass spectrometry (IDMS) approach, with gas
      chromatography high resolution mass spectrometry (GC-HRMS) and gas chromatography
      tandem mass spectrometry (GC-MS/MS). Statistical analysis (one-way ANOVA) showed
      excellent agreement of the analytical data sets generated from the two mass
      spectrometric detections. The characterization methods have also been
      satisfactorily applied in an Asia-Pacific Metrology Program (APMP)
      interlaboratory comparison study. Both the GC-HRIDMS and GC-IDMS/MS methods
      proved to be sufficiently reliable and accurate for certification purpose. The
      certified value of cypermethrin in dry mass fraction was 148 MUg kg(-1) and the
      associated expanded uncertainty was 14MUg kg(-1). The uncertainty budget was
      evaluated from sample in homogeneity, long-term and short-term stability and
      variability in the characterization procedure. GLHK-11-01a is primarily developed
      to support the local and wider testing community on need basis in quality
      assurance work and in seeking accreditation.

PMID- 22405309
TI  - Comparison of liquid chromatography-microchip/mass spectrometry to conventional
      liquid chromatography-mass spectrometry for the analysis of steroids.
AB  - The feasibility of a microfluidic-based liquid chromatography-electrospray
      ionization/mass spectrometric system (HPLC-Chip/ESI/MS) was studied and compared
      to a conventional narrow-bore liquid chromatography-electrospray ionization/mass
      spectrometric (LC-ESI/MS) system for the analysis of steroids. The limits of
      detection (LODs) for oxime derivatized steroids, expressed as concentrations,
      were slightly higher with the HPLC-Chip/MS system (50-300 pM) using an injection
      volume of 0.5 MUL than with the conventional LC-ESI/MS (10-150 pM) using an
      injection volume of 40 MUL. However, when the LODs are expressed as injected
      amounts, the sensitivity of the HPLC-Chip/MS system was about 50 times higher
      than with the conventional LC-ESI/MS system. The results indicate that the use of
      HPLC-Chip/MS system is clearly advantageous only in the analysis of low-volume
      samples. Both methods showed good linearity and good quantitative and
      chromatographic repeatability. In addition to the instrument comparisons with
      oxime derivatized steroids, the feasibility of the HPLC-Chip/MS system in the
      analysis of non-derivatized and oxime derivatized steroids was compared. The HPLC
      Chip/MS method developed for non-derivatized steroids was also applied to the
      quantitative analysis of 15 mouse plasma samples.

PMID- 22405310
TI  - Fission track-secondary ion mass spectrometry as a tool for detecting the
      isotopic signature of individual uranium containing particles.
AB  - A fission track technique was used as a sample preparation method for subsequent
      isotope abundance ratio analysis of individual uranium containing particles with
      secondary ion mass spectrometry (SIMS) to measure the particles with higher
      enriched uranium efficiently. A polycarbonate film containing particles was
      irradiated with thermal neutrons and etched with 6M NaOH solution. Each uranium
      containing particle was then identified by observing fission tracks created and a
      portion of the film having a uranium containing particle was cut out and put onto
      a glassy carbon planchet. The polycarbonate film, which gave the increases of
      background signals on the uranium mass region in SIMS analysis, was removed by
      plasma ashing with 200 W for 20 min. In the analysis of swipe samples having
      particles containing natural (NBL CRM 950a) or low enriched uranium (NBL CRM
      U100) with the fission track-SIMS method, uranium isotope abundance ratios were
      successfully determined. This method was then applied to the analysis of a real
      inspection swipe sample taken at a nuclear facility. As a consequence, the range
      of (235)U/(238)U isotope abundance ratio between 0.0276 and 0.0438 was obtained,
      which was higher than that measured by SIMS without using a fission track
      technique (0.0225 and 0.0341). This indicates that the fission track-SIMS method
      is a powerful tool to identify the particle with higher enriched uranium in
      environmental samples efficiently.

PMID- 22405311
TI  - Mapping of sulfur metabolic pathway by LC Orbitrap mass spectrometry.
AB  - For the first time a liquid chromatography method with high resolution mass
      spectrometric detection has been developed for the simultaneous determination all
      key metabolites of the sulfur pathway in yeast, including all thiolic (cysteine
      (Cys), homocysteine (HCys), glutathione (GSH), cysteinyl-glycine (Cys-Gly), gamma
      glutamyl-cysteine (Glu-Cys)) and non-thiolic compounds (methionine (Met), s
      adenosyl-methionine (AdoMet), s-adenosyl-homocysteine (AdoHcy), and cystathionine
      (Cysta)). The developed assay also permits the speciation and selective
      determination of reduced, oxidized and protein bound fractions of all of the five
      thiols. Iodoacetic acid (IAA) was chosen as the derivatizing reagent. Thiols were
      extracted from sub-mg quantities of yeast using hot 75% ethanol. The detection
      limits were in the range of 1-12 nmol L(-1) for standard solution (high
      femotomole, absolute), except AdoMet (116 nmol L(-1)), which was unstable. In
      freshly harvested yeast, most of the thiols were in the reduced forms and low
      levels of protein-bound GSH and Glu-Cys were found. In a selenium enriched yeast,
      the thiols were mainly in the oxidized forms, and a significant amount of protein
      bound Cys, HCys, GSH, Cys-Gly and Glu-Cys were found. The method was also applied
      to the metabolic study of the adaptive response of Saccharomyces cerevisiae to
      hydrogen peroxide, cadmium, and arsenite, and the change in concentration of
      thiols in the sulfur pathway was monitored over a period of 4h.

PMID- 22405312
TI  - Development and validation of an open screening method for diuretics, stimulants
      and selected compounds in human urine by UHPLC-HRMS for doping control.
AB  - A new doping control screening method for the analysis of diuretics and
      stimulants using ultra high pressure liquid chromatography-high resolution
      Orbitrap mass spectrometry has been developed. The screening was performed in
      full scan MS with scan-to-scan polarity switching which allowed to detect more
      than 120 target analytes. Sample preparation was limited to 10-fold dilution of
      the urine into the internal standard solution followed by injection. Total run
      time per sample was 10 min. Validation of the method yielded detection limits for
      diuretics between 25 and 250 ng mL(-1) and for stimulants between 5 and 500 ng
      mL(-1). The screening method has been implemented in routine doping control.

PMID- 22405313
TI  - High-performance liquid chromatography with fluorescence detection and ultra
      performance liquid chromatography with electrospray tandem mass spectrometry
      method for the determination of indoleamine neurotransmitters and their
      metabolites in sea lamprey plasma.
AB  - We present a comparison of two sensitive methods, HPLC with fluorescence detector
      (HPLC/FLD) and UPLC with electrospray tandem mass spectrometry (UPLC/MS/MS), for
      the determination of indoleamine neurotransmitters (NTs) and their metabolites in
      sea lamprey plasma samples. Liquid-liquid extraction (LLE) and solid-phase
      extraction (SPE) were also tested for recovery and matrix effect. The recoveries
      of SPE determined by HPLC/FLD and UPLC/MS/MS ranged from 75 to 123% and 78 to
      105%, respectively, while the recoveries of LLE ranged from 45 to 73% and 48 to
      75%, respectively. SPE combined with HPLC/FLD and UPLC/MS/MS to determine the
      target analytes in plasma samples were validated of the sensitivity,
      reproducibility, accuracy and precision. Both methods exhibited excellent
      linearity in the range of 0.2-50 ng mL(-1) for all analytes. The limits of
      detection (LOD) varied from 0.04 ng mL(-1) to 0.13 ng mL(-1) for HPLC/FLD method
      and 0.003 ng mL(-1) to 0.02 ng mL(-1) for UPLC/MS/MS method. The inter-day
      accuracy ranged from 82.5 to 127.0% for HPLC/FLD and 93.0 to 113.0% for
      UPLC/MS/MS. The inter-day precision ranged from 9.9 to 32.3% for HPLC/FLD and 5.4
      to 13.2% for UPLC/MS/MS. These results demonstrated that the values obtained by
      both methods were within the satisfactory range and the UPLC/MS/MS method
      provided more accurate and precise measurements than HPLC/FLD method. The
      comparison is of great importance to determine the available detectors,
      considering the complexity and expensiveness versus quality parameters. These two
      methods were applied to the analysis of four important indoleamine
      neurotransmitter analytes (5-hydroxytryptamine, 5-hydroxyindole-3-acetic acid,
      tryptamine and melatonin) in sea lamprey plasma samples.

PMID- 22405314
TI  - CdTe quantum dots functionalized with 4-amino-2,2,6,6-tetramethylpiperidine-N
      oxide as luminescent nanoprobe for the sensitive recognition of bromide ion.
AB  - A novel bromide ion-selective modified nanoprobe sensor based on 4-amino-2,2,6,6
      tetramethylpiperidine-N-oxide (4AT)-functionalized CdTe quantum dots (QDs-4AT)
      has been developed. Fluorescence quenching of the QDs by 4AT was observed. The
      functionalized QDs-4AT nanoprobe allowed a highly sensitive determination of
      bromide ion via analyte-induced change in the photoluminescence (fluorescence
      recovery) of the modified QDs. A detection limit of 0.6 nM of bromide ion was
      obtained, while the interfering effect of other inorganic cations and anions was
      investigated to examine the selectivity of the nanoprobe. The linear range was
      between 0.01 and 0.13 MUM. Combined fluorescence lifetime and electron
      paramagnetic resonance measurements confirmed electron transfer processes between
      bromide ion and QDs-4AT.

PMID- 22405315
TI  - Selective and sensitive determination of peptides using 3,4-dihydroxyphenylacetic
      acid as a fluorogenic reagent.
AB  - A novel fluorescence (FL) reaction for N-terminal Gly-containing peptides has
      been developed using 3,4-dihydroxyphenylacetic acid (3,4-DHPAA). The reaction of
      the peptides with 3,4-DHPAA was carried out in borate buffer (pH 8.0) in the
      presence of sodium periodate at 37 degrees C for 10 min, and the FL was measured
      with a spectrofluorimeter at the excitation and emission wavelengths of 370 nm
      and 465 nm, respectively. The 3,4-DHPAA reagent generated particularly strong FL
      for peptides containing Gly at their N-termini. When various other bio
      substances, such as amino acids, sugars, nucleic bases, nucleotides, and
      proteins, were reacted with 3,4-DHPAA, no FL was observed. Under optimized
      reaction conditions, the lower detection limit of 0.25 MUmol L(-1) was obtained
      for the N-terminal Gly-containing peptides of Gly-Pro (GP) and Gly-Pro-Pro (GPP),
      which gave 3 times greater FL intensity than that observed for the reagent blank.
      The proposed reaction with 3,4-DHPAA as a fluorogenic reagent is selective and
      sensitive for the detection of N-terminal Gly-containing peptides, and therefore,
      this method could be a useful tool for the determination of these particular
      oligopeptides.

PMID- 22405316
TI  - Development of a chemiluminescence-based quantitative lateral flow immunoassay
      for on-field detection of 2,4,6-trinitrotoluene.
AB  - Simple, rapid and highly sensitive assays, possibly allowing on-site analysis,
      are required in the security and forensic fields or to obtain early signs of
      environmental pollution. Several bioanalytical methods and biosensors based on
      portable devices have been developed for this purpose. Among them, Lateral Flow
      ImmunoAssays (LFIAs) offer the advantages of rapidity and ease of use and, thanks
      to the high specificity of antigen-antibody binding, allow greatly simplifying
      and reducing sample pre-analytical treatments. However, LFIAs usually employ
      colloidal gold or latex beads as labels and they rely on the formation of colored
      bands visible by the naked eye. With this assay format, only qualitative or semi
      quantitative information can be obtained and low sensitivity is achieved.
      Recently, the use of enzyme-catalyzed chemiluminescence detection in LFIA has
      been proposed to overcome these problems. In this work, we describe the
      development of a quantitative CL-LFIA assay for the detection of 2,4,6
      trinitrotoluene (TNT) in real samples. Thanks to the use of a portable imaging
      device for CL signal measurement based on a thermoelectrically cooled CCD camera,
      the analysis could be performed directly on-field. A limit of detection of 0.2
      MUg mL(-1) TNT was obtained, which is five times lower than that obtained with a
      previously described colloidal gold-based LFIA developed employing the same
      immunoreagents. The dynamic range of the assay extended up to 5 MUg mL(-1) TNT
      and recoveries ranging from 97% to 111% were obtained in the analysis of real
      samples (post blast residues obtained from controlled explosion).

PMID- 22405317
TI  - Polymeric imidazolium ionic liquids as valuable stationary phases in gas
      chromatography: chemical synthesis and full characterization.
AB  - Seven new functionalized polymerizable ionic liquids were chemically prepared,
      and later applied for the preparation of polymeric stationary phases in gas
      chromatography. These coated GC columns, which exhibited good thermal stabilities
      (240-300 degrees C) and very high efficiencies (3120-4200 plates/m), have been
      characterized using the Abraham solvation parameter model. The chromatographic
      behavior of these polymeric IL columns has been deeply studied observing
      excellent selectivities in the separation of many organic substances such as
      alkanes, ketones, alcohols, amines or esters in mixtures of polar and non polar
      solvents or fragrances. Remarkably, the challenging separation of xylene isomers
      has been possible using a bis(trifluoromethylsulfonyl)amide based imidazolium IL
      coated column as a gas chromatography stationary phase.

PMID- 22405318
TI  - Characterization of At- species in simple and biological media by high
      performance anion exchange chromatography coupled to gamma detector.
AB  - Astatine is a rare radioelement belonging to the halogen group. Considering the
      trace amounts of astatine produced in cyclotrons, its chemistry cannot be
      evaluated by spectroscopic tools. Analytical tools, provided that they are
      coupled with a radioactive detection system, may be an alternative way to study
      its chemistry. In this research work, high performance anion exchange
      chromatography (HPAEC) coupled to a gamma detector (gamma) was used to evaluate
      astatine species under reducing conditions. Also, to strengthen the reliability
      of the experiments, a quantitative analysis using a reactive transport model has
      been done. The results confirm the existence of one species bearing one negative
      charge in the pH range 2-7.5. With respect to the other halogens, its behavior
      indicates the existence of negative ion, astatide At(-). The methodology was
      successfully applied to the speciation of the astatine in human serum. Under
      fixed experimental conditions (pH 7.4-7.5 and redox potential of 250 mV) astatine
      exists mainly as astatide At(-) and does not interact with the major serum
      components. Also, the method might be useful for the in vitro stability
      assessment of (211)At-labeled molecules potentially applicable in nuclear
      medicine.

PMID- 22405319
TI  - Is hydroxyethyl starch 130/0.4 safe?
AB  - It is heavily debated whether or not treatment with hydroxyethyl starch 130/0.4
      contributes to the development of acute kidney failure in patients with severe
      sepsis. In the previous issue of Critical Care, Muller and colleagues report no
      association between initial resuscitation with hydroxyethyl starch 130/0.4 and
      renal impairment in a cohort of septic patients. Can we then consider
      hydroxyethyl starch 130/0.4 a safe intervention? The answer is no - observational
      data should be interpreted with caution and should mainly be used to identify
      risks, while safety must be assessed in randomised clinical trials. With these
      factors in mind, Muller's data associate the use of vasopressors with poor
      outcome, underlining the need for further randomised clinical trials to assess
      the potential harmful effects of common interventions in the critically ill.

PMID- 22405320
TI  - Posterior capsular opacification in patients with pseudoexfoliation syndrome: a
      long-term perspective.
AB  - PURPOSE: To compare posterior capsular opacification in patients with and without
      pseudoexfoliation syndrome 6-7 years following surgery. METHODS: Forty-four eyes
      of 44 patients with pseudoexfoliation syndrome who underwent cataract surgery
      with phacoemulsification in 2001 and 2002 were available for follow-up in 2008.
      These patients were compared to 86 age- and gender-matched patients (86 eyes)
      without pseudoexfoliation syndrome who had surgery during the same time period.
      Posterior capsule opacification was assessed using digital retroillumination
      photography. The images were analysed with a software program (POCOman) to
      determine the extent and severity of the capsular opacification. RESULTS:
      Percentage and severity of posterior capsular opacification within the central
      4.0 and 1.3 mm of the optical zone were compared in eyes with and without
      pseudoexfoliation syndrome. Neither of these results were statistically
      significant. Before the re-examination in 2008, neodymium:yttrium-aluminium
      garnet laser posterior capsulotomy had been conducted in 16% (n = 7) of eyes with
      pseudoexfoliation syndrome, as well as in 16% (n = 14) of eyes without
      pseudoexfoliation syndrome. CONCLUSION: Our study indicates that, with
      phacoemulsification, development of long-term posterior capsular opacification is
      not increased in patients with pseudoexfoliation syndrome after uncomplicated
      cataract surgery.

PMID- 22405321
TI  - Species and tissue-specificity of prokinetic, laxative and spasmodic effects of
      Fumaria parviflora.
AB  - BACKGROUND: Fumaria parviflora Linn. (Fumariaceae), is a small branched annual
      herb found in many parts of the world including Saudi Arabia and Pakistan. This
      study was designed to provide pharmacological basis for the medicinal use of
      Fumaria parviflora in gut motility disorders. METHODS: The in-vivo prokinetic and
      laxative assays were conducted in mice. Isolated intestinal preparations (ileum
      and jejunum) from different animal species (mouse, guinea-pig and rabbit) were
      separately suspended in tissue baths containing Tyrode's solution bubbled with
      carbogen and maintained at 37 degrees C. The spasmogenic responses were recorded
      using isotonic transducers coupled with PowerLab data acquisition system.
      RESULTS: The aqueous-methanol extract of Fumaria parviflora (Fp.Cr), which tested
      positive for the presence of alkaloids, saponins, tannins and anthraquinones
      showed partially atropine-sensitive prokinetic and laxative activities in the in
      vivo in mice at 30 and 100 mg/kg. In the in-vitro studies, Fp.Cr (0.01-1 mg/ml)
      caused a concentration-dependent atropine-sensitive stimulatory effect both in
      mouse tissues (jejunum and ileum), and rabbit jejunum but had no effect in rabbit
      ileum. In guinea-pig tissues (ileum and jejunum), the crude extract showed a
      concentration-dependent stimulatory effect with higher efficacy in ileum and the
      effect was partially blocked by atropine, indicating the involvement of more than
      one types of gut-stimulant components (atropine-sensitive and insensitive). This
      could be a plausible reason for the greater efficacy of Fp.Cr in gut preparations
      of guinea-pig than in rabbit or mouse. CONCLUSIONS: This study shows the
      prokinetic, laxative and spasmodic effects of the plant extract partially
      mediated through cholinergic pathways with species and tissue-selectivity, and
      provides a sound rationale for the medicinal use of Fumaria parviflora in gut
      motility disorders such as, indigestion and constipation. This study also
      suggests using different species to know better picture of pharmacological
      profile of the test material.

PMID- 22405322
TI  - Proportion of extended-spectrum beta-lactamase-producing Enterobacteriaceae in
      community setting in Ngaoundere, Cameroon.
AB  - BACKGROUND: There is no information regarding the resistance mechanisms of
      extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in community
      setting in Cameroon. The current study aimed to determine the proportion of ESBLs
      in Enterobacteriaceae isolated in the community and to analyse some risk factors
      associated with ESBL carriage. METHODS: Faecal samples were collected from 208
      different outpatients and 150 healthy student volunteers between 3 January and 3
      April 2009. Enterobacterial isolates resistant to third-generation cephalosporins
      were screened for ESBL production by the double-disk synergy test. Presumptive
      ESBL-producing isolates with positive synergy test were identified by Mass
      Spectrometry using the BioTyper MALDI-TOF. For such ESBL positive isolates,
      antibiotic susceptibility was determined by the Vitek 2 system. PCR and
      sequencing were performed for the detection of different types of ESBL genes in
      presumptive ESBL-producing isolates. Statistical methods were used for the
      univariate calculation of risk factors. RESULTS: During the study period, a total
      of 358 faecal samples were analysed; 58 of such samples (16%) showed an ESBL
      phenotype and were confirmed by PCR. The proportion of ESBL producers in faecal
      carriage was statistically different between outpatients and student volunteers
      (23.1% vs. 6.7%: p < 0.000). According to a univariate analysis, previous use of
      antibiotics (ciprofloxacin) appeared to be a risk factor for ESBL carriage (p <
      0.05).Escherichia coli was the species most frequently isolated among the ESBL
      producers in outpatients (66.7%) and student volunteers (90%). Isolates showed
      additional resistance to gentamicin, ciprofloxacin and
      trimethoprim/sulfamethoxazole but none of them was resistant to temocillin,
      amikacin or meropenem. Most of the strains (97%) produced a CTX-M group 1 enzymes
      [CTX-M-15 (98%) or CTX-M-1 (2%)] and the remaining strains produced SHV-12 enzyme
      (3%). CONCLUSIONS: The use of drugs such as amoxicillin, ciprofloxacin and
      trimethoprim/sulfamethoxazole does not seem appropriate for empirical treatment
      because of emerging resistance. The implementation in Cameroon or in other
      African countries of methods of screening ESBL-producing organisms in routine
      laboratories is of great importance in order for us to offer patients appropriate
      treatment and for infection control efforts to succeed.

PMID- 22405323
TI  - New and novel intrinsic host repressive factors against HIV-1: PAF1 complex,
      HERC5 and others.

PMID- 22405324
TI  - [Tropical sprue in an expatriate].
AB  - INTRODUCTION: Tropical sprue is a postinfective malabsorption syndrome that
      occurs in some tropical endemic areas. CASE REPORT: A 65-year-old Caucasian
      patient, with no significant past medical history, living in Cambodia for 10
      years, presented with a 23 kg weight loss and chronic diarrhea. Clinical
      examination was unremarkable. Laboratory tests showed a moderate nutritional
      deficiency syndrome. The upper gastrointestinal endoscopy showed duodenal villous
      atrophy and histological analysis confirmed subtotal villous atrophy with
      important intraepithelial lymphocytosis. The diagnosis of tropical sprue was
      considered on the epidemiological, clinical and biological context, and the
      absence of other cause of villous atrophy. A three-month duration treatment with
      antibiotics, folic acid and vitamin B12 was initiated. The clinical course was
      favorable with disappearance of diarrhea in 15 days. One year later, the patient
      had resumed his usual weight, and laboratory tests and duodenal biopsies were
      normal. CONCLUSION: The diagnosis of tropical sprue should be systematically
      discussed in any malabsorption syndrome with villous atrophy in a patient living
      or having lived in the tropics.

PMID- 22405325
TI  - [Hepatitis E: an emerging disease].
AB  - The hepatitis E virus is endemic in countries with poor sanitation, where it has
      many similarities with the hepatitis A virus. It causes a strictly human, feco
      oral transmitted, acute, self-limited hepatitis in young adults. The outcome is
      excellent, except in pregnant women and cirrhotic patients, who experience a high
      mortality rate. The first cases described in industrialized countries were
      travellers coming from endemic areas. However, there is now growing evidence that
      locally-acquired hepatitis E is common in these areas, where it is an emergent
      disease, despite it is still misdiagnosed. In industrialized countries, hepatitis
      E spreads sporadically and has a predilection for elderly men with comorbidity,
      particularly chronic liver diseases. The mortality seems to be higher in this
      population. In these areas, hepatitis E is due to the genotype 3 virus that is
      thought to be zoonotically transmitted by pigs and wild boar. Hepatitis E may
      evolve towards a chronic infection in immunocompromised subjects, particularly in
      solid organ-transplanted patients. In case of chronic infection, it may cause
      liver fibrosis and cirrhosis. The diagnosis of hepatitis E is based on
      serological tests (IgM and IgG) and detection of the viral genome by reverse
      transcription polymerase chain reaction (RT-PCR) on blood and stools. Acute
      hepatitis E does not require any treatment but in chronically infected patients,
      a sustained viral response and finally a definitive viral clearance has been
      observed after a three-month course of low-dose ribavirin (600 to 800 mg/day).
      Two vaccines underwent successful human trials but are not yet commercially
      available.

PMID- 22405326
TI  - The comparison of insulin resistance frequency in patients with recurrent early
      pregnancy loss to normal individuals.
AB  - BACKGROUND: Patients with >= 3 recurrent spontaneous miscarriages are classified
      as having RSM. Polycystic ovary syndrome (PCOS) is associated with insulin
      resistance (IR). The purpose of this study is to evaluate the association of IR
      and RMS. METHODS: Present case- control prospective study was performed on 100
      women in control group (with a history of at a live birth and no history of one
      more abortion) and study group (with a history of >= 3 RMS) who were not diabetes
      and PCOS. Two groups matched in base of age and body mass index. Blood was
      withdrawn from the case and control patients for the determination of the fasting
      blood glucose (FG), fasting insulin (FI) levels and ultrasonography was performed
      on all the patients. RESULTS: The observed differences between age, FG and FG to
      FI ratio levels in case and control groups were not significant (p > 0.05) but it
      was significant about fasting insulin (p = 0.0119). FI of < 20 MUu/ml or >= 20
      MUu/ml in case and control group was significant (Chi-square: 4.083, p: 0.0433,
      odds ratio: 4.4386, CI95% = 1.1541 to 17.0701), whereas the difference between
      absolute and proportional frequency of patients with FG to FI ratio of < 4.5 and
      >= 4.5 in case and control groups was not significant (Chi-square: 2.374, p =
      0.123). CONCLUSION: Current study showed that in women with RPL, in Iranian race
      like Americans, frequency of insulin resistance in high, therefore there is a
      probability of the degree of insulin resistance in women with RPL.

PMID- 22405327
TI  - Cerebral edema in acute ischemic stroke patients treated with intravenous
      thrombolysis.
AB  - BACKGROUND: Cerebral edema (CED) deteriorates outcome of ischemic stroke
      patients, and there is no effective medical treatment. Limited data exist on
      cerebral edema after stroke thrombolysis. AIMS: We aimed to analyze impact of
      cerebral edema on the outcome of thrombolysis-treated patients. METHODS: Our
      cohort included 943 thrombolysis-treated ischemic stroke patients at the Helsinki
      University Central Hospital (1995-2008). Cerebral edema represented focal brain
      swelling up to 1/3 (CED-1) or greater than 1/3 (CED-2) of the hemisphere, or
      midline shift (CED-3). We studied baseline parameters associated with development
      of cerebral edema and association of cerebral edema with three-month outcome
      (modified Rankin Scale, mRS). RESULTS: On control imaging, CED-1 was present in
      167 (17.7%), CED-2 in 40 (4.2%), and CED-3 in 53 (5.6%) patients. Compared with
      patients without edema (n = 683), patients with cerebral edema had higher
      baseline National Institutes of Health Stroke Scale scores, more often hyperdense
      cerebral artery sign or early infarct signs on admission computerized tomography,
      and received thrombolysis later. Cerebral edema was independently associated with
      poor outcome (mRS 3-6) and mortality, whereas favorable outcome (mRS 0-2) was
      observed in 77 (46%), 5 (13%), and 3 (6%) patients with CED 1, 2, and 3,
      respectively. Anti-edema treatment was considered necessary and administered to
      49/260 (19%) patients; only five had favorable outcome. CONCLUSIONS: Cerebral
      edema is frequent (28%) among thrombolysis-treated ischemic stroke patients,
      occurring in severe forms in 10%. Higher baseline National Institutes of Health
      Stroke Scale, presence of hyperdense cerebral artery sign or early infarct signs,
      and longer treatment delays are associated with edema development. Edema is a
      strong independent predictor of three-month outcome. Effect of anti-edema
      treatment was modest.

PMID- 22405328
TI  - Natural distribution and co-infection patterns of microsporidia parasites in the
      Daphnia longispina complex.
AB  - Microsporidia are intracellular parasites, frequently infecting the planktonic
      crustacean Daphnia. Questioning the ability to detect and identify microsporidia
      with conventional microscopic techniques, we applied molecular methods in order
      to investigate the distribution and co-infection patterns of this parasite among
      8 communities of the Daphnia longispina hybrid complex. Eight microsporidian taxa
      were detected, including 3 that previously had not been characterized
      genetically. Microsporidian communities from nearby lakes were found to be more
      similar to each other, apparently due to short distance dispersal via secondary
      hosts. Moreover, we detected seasonal (but not interannual) changes in
      microsporidian community structure. With some microsporidia being host-specific,
      these changes might have resulted from seasonal changes in host taxon and clonal
      composition. The 2 dominant and closely related parasite species were found
      mainly in single infections, whereas another pair of related microsporidians was
      found predominantly in co-infections; suggesting species-level differences in the
      ability to colonize infected hosts. By applying molecular methods, we were not
      only able to unambiguously identify parasite taxa but also to reveal multiple
      infections that otherwise would have remained undetected. Given the increased
      level of accuracy and sensitivity, we highly recommend molecular approaches in
      future parasite surveys of Daphnia infections.

PMID- 22405329
TI  - The predictive role of early activation of natural killer cells in septic shock.
AB  - Recently, several studies about the role of natural killer (NK) cells in sepsis
      have been highlighted. In an earlier study, we characterized the abnormalities of
      circulating lymphocytes in 52 patients with septic shock during the first 28 days
      in the intensive care unit. Our results confirm and expand some previous reports.
      We found that patients who did not survive exhibited less NK cell (CD3-CD56+)
      depletion than survivors and that these NK cells expressed CD69+ and CD57+. These
      data demonstrate that NK cells are key participants in septic shock because
      patients who survived have more depletion and expressed less early activation and
      differentiation.

PMID- 22405330
TI  - Ocular phenotype of CORD5, an autosomal dominant retinal dystrophy associated
      with PITPNM3 p.Q626H mutation.
AB  - PURPOSE: To describe in detail the phenotype of CORD5 in two families segregating
      a mutation c.1878G>C (p.Q626H) in the PITPNM3 gene. METHODS: The study included
      35 individuals from two different families of Swedish origin, all heterozygous
      for a PITPNM3 p.Q626H mutation. All participants underwent ophthalmological
      examination including kinetic perimetry, and in selected cases adaptometry,
      colour vision tests and optical coherence tomography (OCT). Electrophysiological
      studies were also performed. In some cases, the data were obtained from medical
      records. RESULTS: The majority of patients showed subnormal visual acuity and
      light sensitivity from childhood. Early signs of macular degeneration were also
      observed. There was a progressive decrease in visual acuity leading to legal
      blindness in early adulthood. Electrophysiological testing showed a progressive
      loss of photoreceptor function restricted mainly to the cones. OCT revealed
      decreased macular thickness with flattened and enlarged fovea. CONCLUSION: Our
      observations of the PITPNM3 p.Q626H mutation carriers confirm that CORD5 is a
      disease not to mix with other retinal degenerations mapped to 17p13. The results
      of our clinical evaluation so far indicate that CORD5 is characterized by
      predominant cone dysfunction without signs of general involvement of the retinal
      pigment epithelium. The rod system also seems to be unaffected. In this sense,
      CORD5 is different from other autosomal dominant CORDs where rod involvement is
      present to some degree in a late phase of the disease. Some intra- and inter
      familial differences regarding the severity of the clinical picture were
      observed.

PMID- 22405331
TI  - Allogenous tendon stem/progenitor cells in silk scaffold for functional shoulder
      repair.
AB  - Tendon stem/progenitor cells (TSPCs) were recently identified within tendon
      tissues. The aim of this study was to investigate TSPC-seeded knitted silk
      collagen sponge scaffold for functional shoulder repair. The multidifferentiation
      potential, proliferation, and immune properties  of TSPCs were investigated in
      vitro, while the efficacy of TSPC-seeded knitted silk-collagen sponge scaffolds
      in promoting rotator cuff regeneration was evaluated in vivo within a rabbit
      model. TSPCs, which exhibited universal stem cell characteristics (i.e.,
      clonogenicity, high proliferative  capacity, and multidifferentiation potential),
      nonimmunogenicity, and immunosuppression, proliferated well on our scaffold in
      vitro. Implantation of allogenous TSPC-seeded scaffolds within a rabbit rotator
      cuff injury model did not elicit an immunological reaction, but instead increased
      fibroblastic  cell ingrowth and reduced infiltration of lymphocytes within the
      implantation sites at 4 and 8 weeks postsurgery. After 12 weeks, the allogenous
      TSPC-treated group exhibited increased collagen deposition and had better
      structural and biomechanical properties compared to the control group.  This
      study thus demonstrated that the allogenous TSPC-seeded knitted silk-collagen
      sponge scaffold enhanced the efficacy of rotator cuff tendon regeneration by
      differentiating into tenocytes, and by secreting anti-inflammatory cytokines that
      prevent immunological rejection. Hence, allogenous  TSPC-seeded knitted silk
      collagen sponge scaffolds can be a clinically useful application for tendon
      tissue engineering.

PMID- 22405332
TI  - Glucosinolate structures in evolution.
AB  - By 2000, around 106 natural glucosinolates (GSLs) were probably documented. In
      the past decade, 26 additional natural GSL structures have been elucidated and
      documented. Hence, the total number of documented GSLs from nature by 2011 can be
      estimated to around 132. A considerable number of additional suggested structures
      are concluded not to be sufficiently documented. In many cases, NMR spectroscopy
      would have provided the missing structural information. Of the GSLs documented in
      the past decade, several are of previously unexpected structures and occur at
      considerable levels. Most originate from just four species: Barbarea vulgaris,
      Arabidopsis thaliana, Eruca sativa and Isatis tinctoria. Acyl derivatives of
      known GSLs comprised 15 of the 26 newly documented structures, while the
      remaining exhibited new substitution patterns or chain length, or contained a
      mercapto group or related thio-functionality. GSL identification methods are
      reviewed, and the importance of using authentic references and structure
      sensitive detection methods such as MS and NMR is stressed, especially when
      species with relatively unknown chemistry are analyzed. An example of qualitative
      GSL analysis is presented with experimental details (group separation and HPLC of
      both intact and desulfated GSLs, detection and structure determination by UV, MS,
      NMR and susceptibility to myrosinase) with emphasis on the use of NMR for
      structure elucidation of even minor GSLs and GSL hydrolysis products. The example
      includes identification of a novel GSL, (R)-2-hydroxy-2-(3
      hydroxyphenyl)ethylglucosinolate. Recent investigations of GSL evolution, based
      on investigations of species with well established phylogeny, are reviewed. From
      the relatively few such investigations, it is already clear that GSL profiles are
      regularly subject to evolution. This result is compatible with natural selection
      for specific GSL side chains. The probable existence of structure-specific GSL
      catabolism in intact plants suggests that biochemical evolution of GSLs has more
      complex implications than the mere liberation of a different hydrolysis product
      upon tissue disruption.

PMID- 22405333
TI  - Medical Image Analysis. Computer assisted interventions. Editorial.

PMID- 22405334
TI  - Fermentation by Lactobacillus enhances anti-inflammatory effect of Oyaksungisan
      on LPS-stimulated RAW 264.7 mouse macrophage cells.
AB  - BACKGROUND: Oyaksungisan (OY) has been used as a traditional drug in east-Asian
      countries. However, its effect on inflammation still remains unknown. In this
      study, to provide insight into the biological effects of OY and OY fermented by
      Lactobacillus, we investigated their effects on lipopolysaccharide (LPS)-mediated
      inflammation in the RAW 264.7 murine macrophage cells. METHODS: The investigation
      was focused on whether OY and fermented OYs could inhibit the production of pro
      inflammatory mediators such as nitric oxide (NO) and prostaglandin (PG) E2 as
      well as the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase
      (COX)-2, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, nuclear factor
      (NF)-kappaB and mitogen-activated protein kinases (MAPKs) in LPS-stimulated RAW
      264.7 cells. RESULTS: We found that OY inhibits a little LPS-induced NO, PGE2,
      TNF-alpha and IL-6 productions as well as the expressions of iNOS and COX-2.
      Interestingly, the fermentation significantly increased its inhibitory effect on
      the expression of all pro-inflammatory mediators. Furthermore, the fermented OYs
      exhibited elevated inhibition on the translocation of NF-kappaB p65 through
      reduced IkappaBalpha degradation as well as the phosphorylations of extracellular
      signal-regulated kinase (ERK), p38 and c-Jun NH2-terminal kinase (JNK) MAPKs than
      untreated control or original OY. CONCLUSIONS: Finally, the fermentation by
      Lactobacillus potentiates the anti-inflammatory effect of OY by inhibiting NF
      kappaB and MAPK activity in the macrophage cells.

PMID- 22405335
TI  - Assessment of HBV flare in a randomized clinical trial in HIV/HBV coinfected
      subjects initiating HBV-active antiretroviral therapy in Thailand.
AB  - BACKGROUND: Hepatic Flare (HF) after initiation of highly active antiretroviral
      therapy (HAART) in HIV-HBV coinfected individuals is well recognized but
      prospective data on predictors and subsequent outcome are limited. METHODS: The
      Tenofovir in HIV-HBV coinfection study was a randomized clinical trial of HBV
      active HAART including lamivudine and/or tenofovir in antiretroviral naive HIV
      HBV individuals in Thailand. RESULTS: Early HF (EHF) was defined as ALT > 5 * ULN
      during the first 12 weeks. EHF was observed in 8 (22%) of individuals at a median
      of 56 days. 6/8 EHF cases were asymptomatic and resolved with HAART continuation,
      however one subject with underlying cirrhosis died following rapid hepatic
      decompensation. EHF was significantly associated with higher baseline ALT (79
      IU/L vs 36 IU/L non-EHF, p = 0.008) and HBV DNA (9.9 log10 c/ml vs 8.4 log10 c/ml
      non EHF, p = 0.009), and subsequent serological change. HBeAg loss occurred in
      75% of EHF cases versus 22% in non-EHF (p = 0.04), and HBsAg loss in 25% of EHF
      cases versus 4% of non-EHF (p = 0.053). CONCLUSION: EHF after HBV active HAART
      initiation was frequently observed in this population. Timing of EHF, association
      with elevated ALT and HBV DNA and high rate of seroconversion are all consistent
      with immune restoration as the likely underlying process. CLINICAL TRIAL NUMBER:
      NCT00192595.

PMID- 22405336
TI  - Herlyn-Werner-Wunderlich syndrome: MRI findings, radiological guide (two cases
      and literature review), and differential diagnosis.
AB  - BACKGROUND: Herlyn-Werner-Wunderlich (HWW) syndrome is a very rare congenital
      anomaly of the urogenital tract involving Mullerian ducts and Wolffian
      structures, and it is characterized by the triad of didelphys uterus, obstructed
      hemivagina and ipsilateral renal agenesis. It generally occurs at puberty and
      exhibits non-specific and variable symptoms with acute or pelvic pain shortly
      following menarche, causing a delay in the diagnosis. Moreover, the diagnosis is
      complicated by the infrequency of this syndrome, because Mullerian duct anomalies
      (MDA) are infrequently encountered in a routine clinical setting. CASES
      PRESENTATION: two cases of HWW syndrome in adolescents and a differential
      diagnosis for one case of a different MDA, and the impact of magnetic resonance
      (MR) imaging technology to achieve the correct diagnosis. CONCLUSIONS: MR imaging
      is a very suitable diagnostic tool in order to perform the correct diagnosis of
      HWW syndrome.

PMID- 22405337
TI  - Biomechanical analysis of locked and non-locked plate fixation of the clavicle.
AB  - INTRODUCTION: During plate fixation of clavicular fractures the brachial plexus
      and subclavian vessels are vulnerable to injury beneath the clavicle. Locking
      plate fixation allows for mono-cortical fixation, theoretically reducing the risk
      of injury to these structures. Biomechanical analysis of the performance of such
      fixation is limited, and this study was designed to explore this further as a
      treatment option in clavicle fractures. MATERIALS AND METHODS: Fixation of
      fifteen simulated mid-shaft fractures was undertaken using a combination of mono
      cortical locked, bicortical locked and bicortical non-locked plating methods in
      cadaveric clavicles. Samples were then tested via three-point bending to
      destruction, and the performance of each with respect to failure load, bending
      stress, bending stiffness and Young's modulus was then analysed. The influence of
      the number of cortices engaged and locking was also assessed. RESULTS: Clavicles
      fixed with monocortical locking plates displayed a significantly lower bending
      stress (12+/-1 MPa) than both the bicortical locking (28+/-3 MPa, p=0.015) and
      non-locking specimens (24+/-3 MPa, p=0.002). Engaging two cortices with the
      fixation produced a significant increase in failure load (291+/-28 N vs 138+/-48
      N, p=0.018) and bending stress (26+/-2 MPa vs 9.9+/-3.5 MPa, p=0.002) compared to
      single cortex fixation. DISCUSSION: The greatest influence upon the performance
      of the fixation was the number of cortices engaged, with bicortical fixation
      performing significantly better than mono-cortical. Whether or not the fixation
      device was a locking one did not have a significant bearing upon the performance.
      CONCLUSION: This in vitro biomechanical analysis demonstrates that mono-cortical
      locked plating fails at significantly lower levels of load and stress than
      bicortical locked and non-locked plating in mid-shaft fractures of the clavicle,
      and caution would therefore be advised in its use as a fixation modality for
      these injuries.

PMID- 22405338
TI  - Functional outcome and mortality in geriatric distal femoral fractures.
AB  - BACKGROUND: Fragility fractures are a major health care problem worldwide. Due to
      the ageing population an increase of distal femoral fractures is to be expected.
      We studied the long-term functional outcome and their influencing factors in
      geriatric patients with LISS-plated distal femoral fractures. PATIENTS AND
      METHODS: A cohort study with functional long-term follow up examination was
      carried out in a level one trauma centre on distal femoral fracture patients 65
      years and older. Of 53 consecutive patients who were treated in our hospital, 43
      patients with a mean age of 80 years met our inclusion criteria. 48.8% died
      within the study period of 5.3 years. On the remaining patients the residential
      status, the Barthel index and the Parker score were assessed. RESULTS: The mean
      Barthel index was 47.7 and the mean Parker score was 3.5. 23% were found to be
      totally housebound and 26% were not able to perform any social activity. Only 18%
      were able to walk unaided. Patients with any medical complication had
      significantly higher mortality rates. Patients with extraarticular fractures had
      better mobility scores. Nursing home residents showed higher mortality rates but
      compared to patients coming from their own home the difference regarding Barthel
      and Parker scores remained non-significant. CONCLUSION: This study documents the
      poor functional long-term outcome of geriatric patients with distal femoral
      fractures. In comparison to other fragility fracture patients it seems that this
      population is at higher risk to die in-hospital during their perioperative
      course. Medical complications have to be avoided as they were found to be
      associated with worse functional outcome and higher mortality rates. An
      osteoporosis therapy may be associated with reduced mortality rates also in these
      patients.

PMID- 22405339
TI  - Effects of SAC on oxidative stress and NO availability in placenta: potential
      benefits to preeclampsia.
AB  - Preeclampsia (PE) is a major cause of fetal growth restriction and perinatal
      mortality, which involves oxidative stress and vasodilator signaling disorder. S
      allyl-L-cysteine (SAC) is one of the most abundant compounds in garlic extracts,
      and possesses several biological activities. This research was designed to
      investigate the protective effects of SAC against H(2)O(2)-induced oxidative
      insults, as well as the effects on NO/cGMP signaling pathway in placenta. We used
      TEV-1 cells and placental explants to detect the effects of SAC. TEV-1 cells and
      human placental explants were separately exposed to SAC, H(2)O(2), or a
      combination of H(2)O(2) and SAC. Intracellular ROS was detected by flow
      cytometry; the NO level was detected by an NO metabolites (NOx) assay; the cGMP
      level was simultaneously measured by the method of radioimmunoassay; the
      expression of eNOS in TEV-1 cells was measured by immunochemistry and Western
      blot. Our findings showed that H(2)O(2) treatment increased ROS productions in
      TEV-1 cells and significantly decreased cGMP and NO level either in TEV-1 cells
      or explants compared to the control groups (p < 0.05). The expression of eNOS in
      TEV-1 cells also significantly decreased in H(2)O(2) treated group compared to
      the control group (p < 0.05). Co-treatment of H(2)O(2) and SAC significantly
      decreased ROS productions, and increased NO, cGMP and eNOS level compared to the
      H(2)O(2) treated alone groups (p < 0.05), which were all reverted back to near
      control levels. Further more, SAC treatment increased NO and cGMP level of TEV-1
      cells and explants in a dose-dependent manner even at non-oxidative stress status
      (p < 0.05). However, when the TEV-1 cells were cultured in the presence of NOS
      inhibitor (L-NAME) and NO donor (SNP), additional SAC treatment still
      significantly increased the NO level in comparison with SAC non-treated group (p
      < 0.05). In conclusion, these results demonstrate that ROS (H(2)O(2)-mediated)
      can induce insults to NO/cGMP pathway, while SAC could antagonize this insult.
      And SAC also possesses the ability to increase NO and cGMP level at non-oxidative
      stress status in TEV-1 cells and placenta explants. SAC is therefore hypothesized
      to be a potential drug for PE treatment.

PMID- 22405340
TI  - Exploring the roles of interaction and flow in explaining nurses' e-learning
      acceptance.
AB  - BACKGROUND: To provide safe and competent patient care, it is very important that
      medical institutions should provide nurses with continuing education by using
      appropriate learning methods. As compared to traditional learning, electronic
      learning (e-learning) is a more flexible method for nurses' in-service learning.
      Hence, e-learning is expected to play a pivotal role in providing continuing
      education for nurses. OBJECTIVES: This study's purpose was to explore the role
      and relevance of interaction factors, intrinsic motivator (i.e., flow), and
      extrinsic motivators (i.e., perceived usefulness (PU) and perceived ease of use
      (PEOU)) in explaining nurses' intention to use the e-learning system. DESIGN:
      Based on the technology acceptance model (TAM) with the flow theory, this study's
      research model presents three types of interaction factors, learner-system
      interaction, instructor-learner interaction, and learner-learner interaction to
      construct an extended TAM to explore nurses' intention to use the e-learning
      system. SETTINGS: Sample data were gathered from nurses at two regional hospitals
      in Taiwan. PARTICIPANTS: A total of 320 questionnaires were distributed, 254
      (79.375%) questionnaires were returned. Consequently, 218 usable questionnaires
      were analyzed in this study, with a usable response rate of 68.125%. METHODS:
      First, confirmatory factor analysis was used to develop the measurement model.
      Second, to explore the causal relationships among all constructs, the structural
      model for the research model was tested by using structural equation modeling.
      RESULTS: First, learner-system interaction, instructor-learner interaction, and
      learner-learner interaction respectively had significant effects on PU, PEOU, and
      flow. Next, flow had significant effects on PU and PEOU, and PEOU had a
      significant effect on PU. Finally, the effects of flow, PU, and PEOU on intention
      to use were significant. CONCLUSIONS: Synthetically speaking, learner-system
      interaction, instructor-learner interaction, and learner-learner interaction can
      indirectly make significant impacts on nurses' usage intention of the e-learning
      system via their extrinsic motivators (i.e., PU and PEOU) and intrinsic motivator
      (i.e., flow).

PMID- 22405341
TI  - Delegating and supervising unregistered professionals: the student nurse
      experience.
AB  - BACKGROUND: Changing models of healthcare have resulted in the need for
      registered nurses to be competent in delegating and supervising the unregistered
      health care assistant. However research evidence suggests nurse education does
      not prepare students for the practicalities of this role. OBJECTIVES: This paper
      reports on undergraduate student nurses' level of preparation when working with
      health care assistants (HCA). It is part of a large scale project, undertaken
      between 2005 and 2011, which explored pre-registration student nurses'
      perceptions of the role of the HCA and how this affects their clinical learning.
      DESIGN: A sequential transformative mixed method research design was adopted.
      SETTING: One higher educational institution in the United Kingdom. PARTICIPANTS:
      Forty-five pre-registration nursing students took part in phase one and 662
      participated in phase two. METHODS: Phase one used focus groups (n=32) and
      interviews (n=13) and phase two used a semi-structured questionnaire. RESULTS:
      Whilst most students reported that they were familiar with the role of the health
      care assistant, findings showed that nurse training did not initially prepare
      students for the realities of clinical practice, however as students progressed
      they became more aware of such issues. For some such skills were learnt on the
      job and they identified a number of barriers they faced when delegating tasks
      such as fear of causing conflict. Overall the lack of initial preparation was
      perceived by participants to be a hindrance to meeting the goals of clinical
      learning and to understanding the dynamics within the nursing hierarchy.
      CONCLUSIONS: Students in this study highlighted gaps in their educational
      programme and clinical experiences regarding their preparation for a delegatory
      and/or supervisory role. Given the importance of such skills, it is imperative
      that universities provide pre-registration student nurses with the education
      necessary to develop delegation strategies and to adapt to their evolving
      professional role.

PMID- 22405342
TI  - Occupational safety training and education for needlestick injuries among nursing
      students in China: intervention study.
AB  - OBJECTIVES: To confirm the effect of occupational safety training and education
      programs (OSTEP) on needlestick injuries (NSIs) among nursing students in China.
      METHODS: Compare the rates and the nature of NSIs before and after OSTEP among
      the nursing students in China. Firstly, questionnaires were delivered to 248
      randomly selected nursing students from seven training hospitals to obtain basic
      information concerning relevant occupational NSIs. Then regular intervention
      measures through OSTEP on 246 nursing students had been introduced for four
      years. And the resultant information concerning relevant occupational NSIs was
      obtained afterwards. Finally, the data analysis was performed using SPSS
      software, version 11.5. RESULTS: The rate of NSIs among these nursing students
      was relatively high before the OSTEP in China (average, 4.65 events/nurse).
      However, it decreased rapidly to 0.16 events/nurse average after the OSTEP.
      Occupational safety awareness and behavior in handling NSIs was improved in
      China. There was a significant difference in the results of Chi-square value
      (P<0.005). CONCLUSIONS: NSIs are common in nursing students in China. The OSTEP
      can reduce NSIs and change practical behavior markedly among nursing students in
      China. We should perform OSTEP on nurse students before and during the clinical
      practice. We must also provide effective preventive measures to reduce this kind
      of problem in future.

PMID- 22405343
TI  - The effect of self-directed learning abilities of student nurses on success in
      Turkey.
AB  - SDL-self-directed learning is a learning method used increasingly in adult
      education. This study was carried out as an instructive effort to examine the
      effects of SDL on the success of students from nursing school. The sample of this
      study was composed of 220 students attending in Nursing School of Dokuz Eyul
      University during the fall semester of 2006. SDL scale including 40 questions was
      used to obtain the data. Kocaman et al. verified and validated the reliability of
      scale in Turkey. The data was evaluated by using Pearson correlation analysis. As
      a result of research, a positive meaningful average relation was found between
      the points of SDL and success of the students. (p<0.01, r: .60). 

PMID- 22405344
TI  - Turkish nursing students' knowledge and perceptions regarding virginity.
AB  - The aim of this study was to describe the level of knowledge and perceptions of
      the Turkish nursing students regarding virginity, the virginity examination and
      the hymen repair. A convenience sample was used for the study purpose. An
      investigator designed questionnaire was administered to a total sample of 781
      undergraduate nursing students originating from two universities in Mersin and
      Gaziantep, Turkey, respectively. The results showed that the participating
      nursing students agreed that a man must marry a virgin woman and the students'
      opinions had been affected by the social pressures and the social values
      regarding virginity. In additon, it was found that the repair of the hymen was
      acceptable by the participating students. The findings of this study addressed
      and highlighted the gap in the knowledge on virginity related violence so as to
      improve the educational programmes and clinical practice within the context of
      preparing nurses for an extended role in violence against women.

PMID- 22405345
TI  - The "farmer" pathologist: a midsummer night's dream.

PMID- 22405346
TI  - Glomus tumor of kidney: differential diagnosis from juxtaglomerular cell tumor.

PMID- 22405348
TI  - Does the acanthocephalan parasite Polymorphus minutus modify the energy reserves
      and antitoxic defences of its intermediate host Gammarus roeseli?
AB  - In disturbed environments, infected organisms have to face both parasitic and
      chemical stresses. Although this situation is common, few studies have been
      devoted to the effects of infection on hosts' energy reserves and antitoxic
      defence capacities, while parasite survival depends on host survival. In this
      study, we tested the consequences of an infection by Polymorphus minutus on the
      energy reserves (protein, lipid and glycogen) and antioxidant defence capacities
      (reduced glutathione, gamma-glutamylcysteine ligase activity) of Gammarus roeseli
      males and females, in the absence of chemical stress. Moreover, malondialdehyde
      concentration was used as a toxicity biomarker. The results revealed that in
      infected G. roeseli, whatever their gender and the sampling month, protein and
      lipid contents were lower, but glycogen contents were higher. This could be
      explained by the fact that the parasite diverts part of the host's energy for its
      own development. Moreover, glutathione concentrations and gamma-glutamylcysteine
      ligase activity were both lower, which could lead to lower antitoxic defence in
      the host. These results suggest negative effects on individuals in the case of
      additional stress (e.g. pollutant exposure). In the absence of chemical stress,
      the lower malondialdehyde level in infected gammarids could imply a probable
      protective effect of the parasite.

PMID- 22405347
TI  - Characterization of magnesium requirement of human 5'-tyrosyl DNA
      phosphodiesterase mediated reaction.
AB  - BACKGROUND: Topo-poisons can produce an enzyme-DNA complex linked by a 3'- or 5'
      phosphotyrosyl covalent bond. 3'-phosphotyrosyl bonds can be repaired by tyrosyl
      DNA phosphodiesterase-1 (TDP1), an enzyme known for years, but a complementary
      human enzyme 5'-tyrosyl DNA phosphodiesterase (hTDP2) that cleaves 5'
      phosphotyrosyl bonds has been reported only recently. Although hTDP2 possesses
      both 3'- and 5'- tyrosyl DNA phosphodiesterase activity, the role of Mg2+ in its
      activity was not studied in sufficient details. RESULTS: In this study we showed
      that purified hTDP2 does not exhibit any 5'-phosphotyrosyl phosphodiesterase
      activity in the absence of Mg2+/Mn2+, and that neither Zn2+ or nor Ca2+ can
      activate hTDP2. Mg2+ also controls 3'-phosphotyrosyl activity of TDP2. In MCF-7
      cell extracts and de-yolked zebrafish embryo extracts, Mg2+ controlled 5'
      phosphotyrosyl activity. This study also showed that there is an optimal Mg2+
      concentration above which it is inhibitory for hTDP2 activity. CONCLUSION: These
      results altogether reveal the optimal Mg2+ requirement in hTDP2 mediated
      reaction.

PMID- 22405350
TI  - Comparison of mean heart rate in anaesthetized dachshunds and other breeds of dog
      undergoing spinal magnetic resonance imaging.
AB  - OBJECTIVE: Clinical experience suggests that dachshunds are prone to bradycardia
      during general anaesthesia (GA). The study investigated mean heart rates in
      anaesthetized dachshunds and other breeds of dog. STUDY DESIGN: Retrospective
      clinical study. ANIMALS: Sixty one dachshunds and 62 dogs of other breeds met
      inclusion criteria. METHODS: Clinical records of small breed dogs undergoing GA
      for spinal Magnetic Resonance Imaging between September 2008 and March 2010 were
      identified and examined. Data collected included drugs administered, baseline
      heart (HR) and respiratory (f(R) ) rates and rectal temperature. The following
      information was noted from anaesthetic records: HR, f(R) , mean non-invasive
      arterial pressure and end-tidal carbon dioxide (Pe'CO(2)) and anaesthetic agent
      (Fe'agent) during the first 60 minutes of anaesthesia; rectal temperature at a
      time closest to the cessation of anaesthesia, ventilatory mode
      (spontaneous/mechanical) and fluid infusion rate. Univariate analysis with
      Student t-test and Fisher's test identified parameters significant in predicting
      a lowered HR. A multivariate analysis investigated their effect on the mean HR
      during GA. RESULTS: No differences were found between groups regarding: age,
      baseline HR, baseline temperature, incidence of hypotension, Fe'agent, mean
      Pe'CO(2) and fluid infusion rate. Body mass was smaller for dachshunds (6.7 +/-
      1.5 kg) compared to other breeds (7.8 +/- 1.8 kg) (p = 0.0005). The lowest HR
      recorded was lower in dachshunds (64 +/- 19 beats minute(-1)) compared to other
      breeds (72 +/- 21 beats minute(-1)) (p = 0.03). Mean HR was lower in dachshunds
      (75 +/- 21 beats minute(-1)) compared to other breeds (84 +/- 21 beats minute(
      1)) (p = 0.02). Post-procedural temperature ( degrees C) was lower in dachshunds
      (35.5 +/- 1.1) compared to other breeds (36.1 +/- 1.2) (p = 0.007) and
      anticholinergics were also administered more frequently (p = 0.026). Multivariate
      analysis identified that breed and mean Pe'CO(2) affected mean HR during
      anaesthesia. CONCLUSION: This study supported our hypothesis that dachshunds have
      a lower mean HR under GA than other small breed dogs.

PMID- 22405351
TI  - Learning curve in the Cut and Paste method for surgery of primary pterygium.
AB  - PURPOSE: To evaluate the learning curve for the surgery of primary nasal
      pterygium with conjunctival autograft using fibrin adhesive (the Cut and Paste
      method). METHODS: The outcomes of the first consecutive 120 primary pterygium
      surgery cases for two surgeons (groups A and B) were investigated retrospectively
      and compared with the first (group C) and second (group D) 120 cases of GK. A and
      B were previously inexperienced in pterygium surgery. Outcome variables were
      surgery time, complications, the number and the temporal distribution of the
      recurrences. The statistics used were moving averages of the recurrences,
      Scheffe's test of means, learning curve analysis according to Wright and
      logarithmic curve fitting to operation time data. The impact of age and sex on
      recurrences was tested using t-tests and chi-square tests. RESULTS: The mean
      surgery time was 17 min for A, 13 min for B and 13 min for GK. There was a
      certain learning curve slope in operation time in groups A and C. The
      postoperative complications were few and acceptable. There were ten (8.9%)
      recurrences in group A, eight (6.8%) in group B, six (5.5%) in group C and five
      (4.6%) in group D. The temporal distribution of the recurrences did not show any
      learning curve. Age and sex had no significant correlation with recurrence rate
      or surgery time (data not shown). CONCLUSIONS: Our study indicates that the Cut
      and Paste technique is easy to learn and master. We did not find a significant
      learning curve regarding surgery time, recurrences or complications. In a
      clinical setting, it is beneficial to let a few, otherwise experienced eye
      surgeons learn the technique.

PMID- 22405352
TI  - Efficacy and safety of initial combination therapy with sitagliptin and
      pioglitazone in patients with type 2 diabetes: a 54-week study.
AB  - AIM: To assess the 54-week efficacy of initial combination therapy with
      sitagliptin and pioglitazone, compared with pioglitazone monotherapy, and to
      assess safety in these groups during the 30 weeks after the dosage of
      pioglitazone was increased from 30 to 45 mg/day, in drug-naIve patients with type
      2 diabetes mellitus and inadequate glycaemic control [haemoglobin A1c (HbA1c) 8
      12%]. METHODS: Following a 24-week, randomized, double-blind, parallel-group
      study (Sitagliptin Protocol 064, Clinicaltrials.gov: NCT00397631; Yoon KH,
      Shockey GR, Teng R et al. Effect of initial combination therapy with sitagliptin,
      a dipeptidyl peptidase-4 inhibitor, and pioglitazone on glycaemic control and
      measures of beta-cell function in patients with type 2 diabetes. Int J Clin Pract
      2011; 65: 154-164) in which patients were treated with the combination of
      sitagliptin 100 mg/day and pioglitazone 30 mg/day or monotherapy with
      pioglitazone 30 mg/day, patients entered a 30-week extension study. In the
      extension study, the pioglitazone dose was increased from 30 to 45 mg/day in both
      groups. Depending upon treatment allocation, patients took one tablet of
      sitagliptin 100 mg or matching placebo daily. Pioglitazone was administered in an
      open-label fashion as a single 45-mg tablet taken once daily. Patients not
      meeting specific glycaemic goals in the extension study were rescued with
      metformin therapy. Efficacy and safety results for the extension study excluded
      data after initiation of rescue therapy. RESULTS: Of the 520 patients initially
      randomized, 446 completed the base study and, of these, 317 entered the
      extension. In this extension study cohort, the mean reductions from baseline in
      HbA1c and fasting plasma glucose (FPG) at the end of the base study (week 24)
      were -2.5% and -62.1 mg/dl with the combination of sitagliptin 100 mg and
      pioglitazone 30 mg versus -1.9% and -48.7 mg/dl with pioglitazone monotherapy. At
      the end of the extension study (week 54), the mean reduction in haemoglobin A1c
      (HbA1c) was -2.4% with the combination of sitagliptin 100 mg and pioglitazone 45
      mg versus -1.9% with pioglitazone monotherapy [between-group difference (95% CI)
      = -0.5% (-0.8, -0.3)] and the mean reduction in FPG was -61.3 mg/dl versus -52.8
      mg/dl, respectively [between-group difference (95% CI) = -8.5 mg/dl (-16.3, 
      0.7)]. Safety and tolerability of initial treatment with the combination of
      sitagliptin and pioglitazone and pioglitazone monotherapy were similar. As
      expected, increases in body weight from baseline were observed in both treatment
      groups at week 54: 4.8 and 4.1 kg in the combination and monotherapy groups,
      respectively [between-group difference (95% CI) = 0.7 kg (-0.7, 2.1)].
      CONCLUSION: In this study, initial combination therapy with sitagliptin 100 mg
      and pioglitazone 30 mg increased to 45 mg after 24 weeks led to a substantial and
      durable incremental improvement in glycaemic control compared with initial
      treatment with pioglitazone monotherapy during a 54-week treatment period. Both
      initial combination therapy with sitagliptin and pioglitazone and pioglitazone
      monotherapy were generally well tolerated (Clinicaltrials.gov: NCT01028391).

PMID- 22405353
TI  - Conjugated linoleic and linolenic acid production kinetics by bifidobacteria
      differ among strains.
AB  - There is great interest in conjugated linoleic acid (CLA) and conjugated
      linolenic acid (CLNA) isomers because of their supposed health-promoting
      properties. Therefore, the differences in production kinetics of CLA and CLNA
      isomers from linoleic acid (LA) and alpha-linolenic acid (alpha-LNA),
      respectively, by bifidobacteria were investigated. Laboratory fermentations,
      supplemented with LA or alpha-LNA in the fermentation medium, were performed with
      Bifidobacterium bifidum LMG 10645, Bifidobacterium breve LMG 11040, B. breve LMG
      11084, B. breve LMG 11613, B. breve LMG 13194, and Bifidobacterium pseudolongum
      subsp. pseudolongum LMG 11595. Conversion of LA and alpha-LNA to CLA and CLNA
      isomers, respectively, started immediately upon addition of the substrate fatty
      acids. During the active growth phase, the c9, t11-CLA isomer and the putative
      c9, t11, c15-CLNA isomer were formed. Further fermentation resulted in a
      reduction in the concentration of c9, t11-CLA and c9, t11, c15-CLNA and the
      subsequent production of the t9, t11-CLA isomer and the putative t9, t11, c15
      CLNA isomer, respectively. Modelling of the growth and metabolite data indicated
      differences in production kinetics among the strains. Some strains displayed a
      high specific conversion of LA and alpha-LNA despite poor growth, whereas other
      strains grew well but displayed lower conversion. Production of specific CLA and
      CLNA isomers by bifidobacteria holds potential for the production of functional
      foods and could contribute to their probiotic properties.

PMID- 22405355
TI  - Lipid composition of wine strains of Saccharomyces kudriavzevii and Saccharomyces
      cerevisiae grown at low temperature.
AB  - Some species of the Saccharomyces genus have shown better adaptation at low
      temperature than the wine yeast Saccharomyces cerevisiae. That is the case of the
      cryophilic yeast Saccharomyces kudriavzevii. Several studies have revealed the
      importance of the lipid composition in the yeast adaptive response at different
      environmental temperatures. Thus we analysed the lipid composition of three S.
      kudriavzevii strains during growth at optimum (28 degrees C) and low temperature
      (12 degrees C), and compared them with different commercial strains; one S.
      cerevisiae strain and two hybrids between S. cerevisiae and S. kudriavzevii. Our
      results show a general increase in the medium-chain fatty acid, triacylglyceride,
      sterol esters and squalene and a decrease in the chain length of the fatty acids,
      in phosphatidic acid and in the ratio
      phosphatidylcholine/phosphatidylethanolamine at low temperatures. The S.
      kudriavzevii strains had higher percentages of medium-chain fatty acids and
      squalene and shorter chain lengths regardless of the growth temperature. This
      differential lipid composition may partially explain the better adaptation of S.
      kudriavzevii at low temperatures. We have also confirmed the better fermentation
      performance of the strains of this species at low temperature, being an appealing
      alternative to S. cerevisiae for cold fermentations.

PMID- 22405356
TI  - Successful writing for clinical teachers.

PMID- 22405354
TI  - Isolation and characterization of multidrug-resistant Klebsiella spp. isolated
      from shrimp imported from Thailand.
AB  - A study was undertaken to isolate and characterize tetracycline and nalidixic
      acid-resistant Klebsiella spp. in farm-raised, imported shrimp sold in the United
      States. Sixty-seven multiple antibiotic-resistant Klebsiella spp. strains were
      isolated from imported shrimp samples. Using morphological and biochemical
      methods, fifty-three strains were tentatively identified as Klebsiella pneumoniae
      and fourteen as K. oxytoca. Although all isolates were resistant to tetracycline,
      only 8 were resistant to nalidixic acid. These 8 isolates were further screened
      by PCR for quinolone resistance genes (qnrA, B, S, gyrA, B and parC). PCR
      protocols failed to amplify any qnr genes. The purified PCR amplicons of gyrA,
      gyrB and parC were sequenced and analyzed for point mutations that confer
      resistance to fluoroquinolone antibiotics. Analysis of the sequences of the gyrA
      amplicons from nalidixic acid-resistant Klebsiella spp. indicated two point
      mutations in gyrA at positions 83 (Ser->Phe) and 87 (Asp->Ala). Sequence analysis
      of the parC amplicons indicated an amino acid change at position 80 (Ser->Ile).
      No mutations were detected in gyrB. Template DNA from all isolates was screened
      for tetracycline resistance genes (tetA-E). Oligonucleotide primers specifically
      targeting a 305-bp region of tetB and a 477-bp region of tetD successfully
      amplified sequences from 91.0 and 44.0% of the isolates, respectively. None of
      the isolates contained tetA, tetC or tetE genes. Plasmids (2.0-16.0kb) were found
      in 23 of the 67 isolates. XbaI-PFGE identified 32 distinct macro restriction
      patterns (mrps) among the 61 multiple drug-resistant Klebsiella spp. that were
      typable. Our results indicate that imported shrimp is a reservoir for multidrug
      resistant Klebsiella spp. and potential health risks posed by such strains should
      not be underestimated.

PMID- 22405357
TI  - Responding to unprofessional behaviours.
AB  - BACKGROUND: Medical educators sometimes have to respond to inappropriate
      behaviours from doctors in training that have the potential to endanger their
      future careers and affect the safety and well-being of their patients. The
      authors led workshops at international meetings using case-based discussion and
      plenary wrap-ups to reinforce and share the learning outcomes. This paper
      summarises key points of difference and common themes about how to manage
      challenging professional behaviours presented by doctors in training that may be
      of value to tutors and clinical educators. CONTEXT: Although the problems
      encountered had elements in common, experiences varied between countries, schools
      and programmes as regards processes, procedures and thresholds for launching an
      investigation. Whereas variations are not unexpected it is important to consider
      the context and background against which decisions are made. Appropriate
      responses must take account of professional, legal and ethical guidelines, where
      they exist. IMPLICATIONS: Major inconsistencies in hearings and investigations
      may not be in anyone's best interests: fairness is core to most notions of
      justice, whether from the perspective of a doctor in training, clinical educator
      or member of the public. Therefore, schools and programmes need to take this into
      account when reviewing processes and procedures. Although the career of a doctor
      in training is important, it is not the only consideration. If systems fail the
      public has a right to be concerned, and striving to ensure that medical students
      graduate to become safe, professional doctors is something of concern to all
      clinical educators.

PMID- 22405358
TI  - Competency and professionalism in medicine.
AB  - BACKGROUND: In this article some definitions of competency and professionalism
      will be discussed, and an overview of existing methods that assess competency and
      professionalism in anaesthesia resident doctors (residents) is provided. In
      addition, we will discuss how progression to professionalism, education in
      anaesthesiology and other medical specialties may be improved using the adult
      skill acquisition model. The goal of this paper is to refine the definitions of
      professionalism and competency, and to propose a new approach to medical
      education. CONTEXT: The terms professionalism and competency are both used in the
      context of education, sometimes interchangeably, adding to the confusion
      surrounding their definitions and application. Competency, from our point of
      view, is the ability to perform a certain task required for a work situation.
      Professionalism includes competencies in addition to the specific behaviours
      required to successfully perform in a certain specialty. Areas in which progress
      in medical education may be achieved include: resident selection; teaching and
      testing of programs (e-education); better use of simulation for skills
      assessment; and teaching and assessment of non-technical skills during residency.
      Medical schools and teaching hospitals should work continuously on creating and
      maintaining a high level of professional culture. IMPLICATIONS: Medical
      knowledge, manual skills and non-technical skills should be used for the
      assessment of professionalism in medical specialties. The necessity to improve on
      the quality of medical care calls for changes in medical education.

PMID- 22405359
TI  - Teaching a fishbowl tutorial: sink or swim?
AB  - BACKGROUND: The fishbowl method is a small group teaching technique in which a
      number of students engage in a discussion while observers form a circle around
      them. We use this method to teach medical interviewing skills, with students
      interviewing a simulated patient (SP) whilst being observed by their peers and a
      clinical tutor. However, there is little evidence to guide teachers on how best
      to structure a fishbowl tutorial. METHODS: Our aim was to develop guidelines for
      teaching medical interviewing skills in the context of a fishbowl tutorial by
      assessing preferred teaching approaches for all participants (students, tutors
      and SPs). Participant preferences for teaching in the fishbowl were established
      using questionnaires designed to seek participants' opinions on various aspects
      of fishbowl tutorials, integrating key areas of difficulty highlighted during SP
      and tutor training sessions. RESULTS: Across most items there was a high degree
      of consistency in the preferences of tutors, students and SPs, which enabled us
      to develop a set of guidelines for running a fishbowl tutorial to be used for our
      teaching programme. DISCUSSION: We found this process to be acceptable to all
      parties and relatively simple to perform. It helped us to define our preferred
      procedures for teaching medical interviewing skills using the fishbowl method.
      The process of gauging participant opinion to develop teaching guidelines is
      appropriate for use by other institutions to inform their teaching practices in
      the fishbowl technique, although the nature of the guidelines may differ across
      teaching settings. Further research is required to determine if the
      implementation of these guidelines improves student satisfaction with fishbowl
      tutorials.

PMID- 22405360
TI  - Benefits of communication skills training after real patient exposure.
AB  - BACKGROUND: The established communication skills training (CST) curriculum
      consists of continuous education, frequent practice with real patients,
      supervision and feedback from medical teachers. The limitation of this curriculum
      is that students have to directly apply the theoretical basis they are provided
      with to real patients. To improve the existing CST curriculum a CST module
      involving simulated patients was introduced in order to develop more complex
      communication skills. METHODS: A new CST module using simulated patients was
      developed and evaluated. The students assessed the module from their own
      perspective using a questionnaire, and compared it with other courses. In
      addition, the communication competencies of the students were assessed with a
      self-report questionnaire before and after the training. RESULTS: The overall
      rating for the course was 5.4 on a six-point Swiss school grade scale, with six
      being the best possible score. The self-assessment showed positive changes after
      the intervention and subjective improvement in knowledge, to varying extents.
      DISCUSSION: For the acquisition of more complex communication skills students
      value being able to practise their skills with simulated patients first, before
      practising with real patients.

PMID- 22405361
TI  - Clinical leadership development requires system-wide interventions, not just
      courses.
AB  - BACKGROUND: This is the third article in a series on clinical leadership and
      medical education. In the first two articles in this series we looked at the
      nature of leadership and examined professional outcomes, standards and competency
      frameworks from around the world that describe what it is we are trying to instil
      in medical students and doctors in postgraduate training. In this article we
      explore current trends in leadership development and describe broad approaches to
      clinical leadership development, highlighting those strategies that are likely to
      be more (or less) successful. METHODS: Narrative review and discussion. RESULTS:
      Key trends and principles for best practice in leadership development are
      identified. Recommendations for the design of leadership development programmes
      are made alongside suggestions for system-wide interventions. DISCUSSION:
      Leadership development should be both drawn from and embedded in work-based
      activities, and as far as possible linked to the development of the organisation
      as a whole. Intervening at the level of the individual may not be enough. System
      wide interventions are required that actively engage students and trainees in the
      practices of management and leadership, and involve them early.

PMID- 22405362
TI  - Building capacity for interprofessional practice.
AB  - BACKGROUND: Evidence indicates that professional development focused on
      collaborative practice can improve the quality of care and patient outcomes in
      specific populations. However, current educational knowledge does not include how
      to teach professionals to provide interprofessional collaborative care. METHODS:
      This paper discusses the design, implementation and evaluation of the
      Interprofessional Collaborative Learning Series (IP-CLS), which provides
      clinicians with interprofessional professional development that promotes
      interprofessional competencies, allowing them to incorporate elements of
      interprofessional collaboration into practice, and creates leaders for
      interprofessional collaborative practice. The IP-CLS was piloted at a regional
      health centre in Ontario. Participants completed an online retrospective before
      and after self-assessment to determine the extent to which the IP-CLS contributed
      to changes in participants' behaviours related to interprofessional
      collaboration. A focus group further explored the extent to which the IP-CLS
      fostered change. RESULTS: Online survey results and an analysis of focus group
      transcripts reveal the strengths of the IP-CLS and the elements that could be
      improved upon. Findings indicate that the IP-CLS has the potential to build
      capacity for interprofessional collaboration. DISCUSSION: The findings indicate
      that the IP-CLS has the potential to build capacity for interprofessional
      collaborative practice, and to help participants incorporate elements of
      interprofessional collaboration into practice.

PMID- 22405363
TI  - Worlds apart: training in rural South Africa.
AB  - BACKGROUND: Reforms in the delivery of surgical and anaesthetic services in the
      UK have reduced the opportunity for trainees to acquire 'hands-on' training.
      These problems are seen in other European countries and in North America.
      CONTEXT: Surgical and anaesthetic services within developed health care systems
      tend to be specialised, and are often consultant led. In rural South Africa there
      is a shortage of surgeons and anaesthetists to service the population, and the
      public health care system is vastly over-burdened. Trauma accounts for a large
      percentage of the surgical and anaesthetic workload. INNOVATION: This report
      compares the anaesthetic and surgical training experience of two first-year
      registrars during a 6-month training period in rural South Africa and a 6-month
      training period in the UK. IMPLICATIONS: Surgical and anaesthetic trainees from
      countries such as the UK can spend an out-of-programme training period in rural
      South Africa, thereby broadening their experience and exposure to trauma. They
      have the opportunity to take on a higher level of responsibility at an earlier
      stage of training, gaining 'hands-on' experience. Similarly, South African
      anaesthetic and surgical trainees can spend an out-of-programme training period
      in the UK, where they can learn the specialist procedures needed in their home
      country.

PMID- 22405364
TI  - Primary care career advice: a student perspective.
AB  - BACKGROUND: In the UK, undergraduate curricula have evolved to include a greater
      proportion of community-based teaching. However, for most students it still
      remains predominantly a hospital-based training experience. With 50 per cent of
      all medical graduates in the UK now expected to work in the community, students
      need to be fully informed about career pathways and opportunities within primary
      care. CONTEXT: A key driver for curriculum change in the UK has been the General
      Medical Council's guidance in Tomorrow's Doctors, which advocates experience in a
      variety of health care settings together with career advice at undergraduate
      level. However, the existing career guidance provision may be inadequate for the
      current needs of students. INNOVATION: We explore what students are doing to
      combat the lack of primary care focused career guidance: from taking a year out
      to intercalate in primary care to setting up and running student-led primary care
      groups. We report on a new UK venture that we hope to launch in consultation with
      national primary care bodies to provide support and guidance for students
      considering a career in primary care. IMPLICATIONS: Primary care-focused career
      advice should be incorporated into the undergraduate curriculum. Student-led
      primary care groups can offer an alternative source of support and guidance.

PMID- 22405365
TI  - Preparedness of Foundation Year 1 doctors in dermatology.
AB  - BACKGROUND: UK medical graduates are required to reach standards defined by the
      General Medical Council (in Tomorrows Doctors) in all specialties, including
      dermatology. AIMS: We assessed the self-reported competence of Foundation Year 1
      (FY1) doctors in the diagnosis and management of skin disease correlated against
      their undergraduate dermatology experience. METHODS: The FY1 doctors attending a
      teaching programme were surveyed at six hospital sites throughout the North
      Western Deanery. Questionnaires were completed on self-reported competence in
      learning outcomes defined by the British Association of Dermatologists (BAD).
      Information recorded previous undergraduate teaching (duration and delivery), and
      whether they felt sufficiently prepared to diagnose and manage patients with skin
      disease in their clinical practice. RESULTS: Of 174 FY1 doctors, 118 attended the
      teaching sessions. All of the attendees completed a questionnaire. Trainees who
      undertook longitudinal placements in dermatology (defined as 10 or more half days
      of clinical experience) regarded themselves significantly more prepared to
      practise for their stage of training: 61 per cent compared with 8.9 per cent
      (chi(2) = 32.8, df = 1, p < 0.05). Furthermore, these trainees rated their
      abilities in basic history taking, clinical examination, management of
      dermatological emergencies and diagnosis of skin malignancy as being greater than
      those who had not experienced longitudinal placements in the specialty.
      CONCLUSIONS: Longitudinal placements in dermatology offer undergraduates
      experience in the diagnosis and management of skin disease that develops
      confidence for foundation practice.

PMID- 22405366
TI  - Handwritten undergraduate case reports.
AB  - BACKGROUND: This article describes a 'back to the future' approach to case 'write
      ups', with medical students producing handwritten instead of word-processed case
      reports during their clinical placements. Word-processed reports had been found
      to have a number of drawbacks, including the inappropriate use of 'cutting and
      pasting', undue length and lack of focus. METHOD: We developed a template to be
      completed by hand, based on the hospital 'clerking-in process', and matched this
      to a new assessment pro forma. An electronic survey was conducted of both
      students and assessors after the first year of operation to evaluate impact and
      utility. RESULTS: The new template was well received by both students and
      assessors. Most students said they preferred handwriting the case reports
      (55.6%), although a significant proportion (44.4%) preferred the word processor.
      Many commented that the template enabled them to effectively learn the structure
      of a case history and to improve their history-taking skills. Most assessors who
      had previously marked case reports felt the new system represented an
      improvement. The average time spent marking each report fell from 23.56 to 16.38
      minutes using the new pro forma. DISCUSSION: Free text comments from the survey
      have led to the development of a more flexible case report template better suited
      to certain specialties (e.g. dermatology). This is an evolving process and there
      will be opportunities for further adaptation as electronic medical records become
      more common in hospital.

PMID- 22405367
TI  - Inter-examiner agreement in clinical evaluation.
AB  - BACKGROUND: The reliability of assessment is an important issue in the evaluation
      of competence in medical and allied health practice, particularly when
      assessments are conducted by multiple examiners. The purpose of this study was to
      examine the agreement between multiple examiners in the assessment of a
      postgraduate physiotherapy student using a specifically designed performance
      evaluation system. METHODS: Seven examiners simultaneously watched a recording of
      a postgraduate student's examination and treatment of one patient. The
      Postgraduate Physiotherapy Performance Assessment (PPPA) form was used to guide
      the assessment of performance in key areas of patient examination and management.
      Each examiner independently recorded a grade for each of five performance
      categories, and these scores were used to guide the global performance grade and
      mark. RESULTS: Five examiners agreed on the global performance grade and four of
      the performance categories. The level of pass grade awarded was more variable,
      with scores in the performance categories spanning two grades, and in one case,
      three grades. The two examiners who were not in agreement with the majority
      consistently awarded higher grades across most performance categories.
      DISCUSSION: This preliminary study has demonstrated majority agreement in global
      performance between multiple examiners when physiotherapy clinical practice is
      assessed against specific performance standards. Not all examiners awarded global
      grades consistent with the majority, and there was greater variability between
      examiners when grading performance in specific aspects of practice. These
      findings highlight the importance of examiner training and review sessions to
      improve inter-examiner agreement in assessments of clinical performance that
      require multiple examiners.

PMID- 22405368
TI  - Being a faculty member of the PSG-FAIMER Regional Institute.

PMID- 22405375
TI  - Drug addiction on the wards: are junior doctors equipped?

PMID- 22405376
TI  - Virtual patients can be used to teach clinical reasoning.

PMID- 22405377
TI  - Predicting the outcome of chronic kidney disease by the estimated nephron number:
      the rationale and design of PRONEP, a prospective, multicenter, observational
      cohort study.
AB  - BACKGROUND: The nephron number is thought to be associated with the outcome of
      chronic kidney disease (CKD). If the nephron number can be estimated in the
      clinical setting, it could become a strong tool to predict renal outcome. This
      study was designed to estimate the nephron number in CKD patients and to
      establish a method to predict the outcome by using the estimated nephron number.
      METHODS/DESIGN: The hypothesis of this study is that the estimated nephron number
      can predict the outcome of a CKD patient. This will be a multicenter, prospective
      (minimum 3 and maximum 5 years follow-up) study. The subjects will comprise CKD
      patients aged over 14 years who have undergone a kidney biopsy. From January 2011
      to March 2013, we will recruit 600 CKD patients from 10 hospitals belonging to
      the National Hospital Organization of Japan. The primary parameter for assessment
      is the composite of total mortality, renal death, cerebro-cardiovascular events,
      and a 50% reduction in the eGFR. The secondary parameter is the rate of eGFR
      decline per year. The nephron number will be estimated by the glomerular density
      in biopsy specimens and the renal cortex volume. This study includes one sub
      cohort study to establish the equation to calculate the renal cortex volume.
      Enrollment will be performed at the time of the kidney biopsy, and the data will
      consist of a medical interview, ultrasound for measurement of the kidney size,
      blood or urine test, and the pathological findings of the kidney biopsy. Patients
      will continue to have medical consultations and receive examinations and/or
      treatment as usual. The data from the patients will be collected once a year
      after the kidney biopsy until March 2016. All data using this study are easily
      obtained in routine clinical practice. DISCUSSION: This study includes the first
      trials to estimate the renal cortex volume and nephron number in the general
      clinical setting. Furthermore, this is the first prospective study to examine
      whether the nephron number predicts the outcome of CKD patients. The results from
      this study should provide powerful new tools for nephrologists in routine
      clinical practice. TRIAL REGISTRATION: UMIN-Clinical Trial Registration,
      UMIN000004784.

PMID- 22405378
TI  - Bioreactor for blood product production.
AB  - The feasibility of ex vivo blood production is limited by both biological and
      engineering challenges. From an engineering perspective, these challenges include
      the significant volumes required to generate even a single unit of a blood
      product, as well as the correspondingly high protein  consumption required for
      such large volume cultures. Membrane bioreactors, such as hollow fiber
      bioreactors (HFBRs), enable cell densities approximately 100-fold greater than
      traditional culture systems and therefore may enable a significant reduction in
      culture working volumes. As cultured  cells, and larger molecules, are retained
      within a fraction of the system volume, via a semipermeable membrane it may be
      possible to reduce protein consumption by limiting supplementation to only this
      fraction. Typically, HFBRs are complex perfusion systems having total volumes
      incompatible  with bench scale screening and optimization of stem cell-based
      cultures. In this article we describe the use of a simplified HFBR system to
      assess the feasibility of this technology to produce blood products from
      umbilical cord blood-derived CD34(+) hematopoietic stem progenitor cells 
      (HSPCs). Unlike conventional HFBR systems used for protein manufacture, where
      cells are cultured in the extracapillary space, we have cultured cells in the
      intracapillary space, which is likely more compatible with the large-scale
      production of blood cell suspension cultures. Using this platform  we direct
      HSPCs down the myeloid lineage, while targeting a 100-fold increase in cell
      density and the use of protein-free bulk medium. Our results demonstrate the
      potential of this system to deliver high cell densities, even in the absence of
      protein supplementation of the bulk medium.

PMID- 22405379
TI  - A marvelous landscape: the endoscopic universe.

PMID- 22405380
TI  - Neuroendoscopy: a modern perspective.

PMID- 22405381
TI  - Delayed vasospasm in aneurysmal subarachnoid hemorrhage.

PMID- 22405382
TI  - The sitting position for neurosurgery: yet another case series confirming safety.

PMID- 22405383
TI  - Types of postoperative drainage for chronic subdural hematoma: to do it on the
      table or under?

PMID- 22405384
TI  - The abducens nerve and skull base surgery.

PMID- 22405385
TI  - Bringing the endovascular neurosurgeon into the neuro-oncology treatment team.

PMID- 22405386
TI  - Lumbar juxtafacet cysts: simply an extension of the lumbar degenerative process.

PMID- 22405387
TI  - Spontaneous disappearance of large herniated disk fragments.

PMID- 22405388
TI  - Lumbar and cervical disc herniations: a common problem, many solutions.

PMID- 22405389
TI  - Surgical treatment of blister-like aneurysms.

PMID- 22405390
TI  - Retethering after filum cutting.

PMID- 22405391
TI  - Subdural hematomas: an analysis of 1181 Kashmiri patients.
AB  - BACKGROUND: We endeavored to analyze patients of subacute and chronic subdural
      hematomas studied in a 4-year period at the Sher-i-Kashmir Institute of Medical
      Sciences, Kashmir, India. METHODS: The study was a retrospective analysis of 1181
      patients of subdural hematomas. Demographic characteristics, clinico-radiologic
      features, operative modalities, and outcome were studied. Acute subdural
      hematomas were excluded from the study. RESULTS: The mean age was 60.4 +/- 12.4
      and males outnumbered females. Chronic subdural collections were more common than
      subacute subdural hematomas and left side predominated. Two burr holes with
      closed-system drainage was used in most patients. Incidence of postoperative
      seizures is very low. Overall recurrence rates were low; however, multilocular
      hematomas had the highest incidence of recurrence. Morbidity and mortality were
      7.53% and 2.96%, respectively. Preoperative neurologic grade correlated with
      outcome. CONCLUSIONS: Subdural hematomas are common in elderly males.
      Preoperative neurologic grade dictates the outcome. Multilocular hematomas have a
      higher chance of recurrence. Craniotomy should be reserved for recurrent
      hematomas, and there may be a scope of craniotomy for multilocular chronic
      subdural hematomas at the outset. Antiepileptic prophylaxis is not routinely
      recommended.

PMID- 22405392
TI  - Intra-arterial delivery of bevacizumab after blood-brain barrier disruption for
      the treatment of recurrent glioblastoma: progression-free survival and overall
      survival.
AB  - BACKGROUND: This prospective, single-center study assesses progression-free
      survival (PFS) and overall survival (OS) in patients with recurrent glioblastoma
      multiforme (GBM) treated with a single dose of superselective intra-arterial
      cerebral infusion (SIACI) of bevacizumab (BV) after blood-brain barrier
      disruption (BBBD). Patients were initially enrolled in our phase I study, for
      which the primary end point was to determine the safety and maximum tolerated
      dose of SIACI BV. METHODS: Fourteen patients with recurrent GBM were recruited
      between August 2009 and November 2010 after failing the standard treatment with
      radiation therapy and temozolomide. None of these patients were previously
      treated with BV. After receiving a single dose of IA BV (2 to 15 mg/kg), standard
      IV BV chemotherapy was continued in 12 of 14 patients (86%). The recently updated
      Response Assessment in Neuro-Oncology Working Group (RANO) criteria were used to
      evaluate PFS, and the Kaplan-Meier estimator was used to evaluate PFS and OS.
      RESULTS: Using RANO criteria, the median PFS in these patients was 10 months. The
      median OS estimation for this cohort was 8.8 months. The OS was less than the PFS
      because 4 patients died without progressing. Toxicity attributed to the IA BV
      treatment was present in 2 patients (wound dehiscence and rash). Another patient
      suffered from seizures 1 week after the SIACI procedure; however, this patient
      had epilepsy before and seizure type/frequency were similar before and after
      therapy. CONCLUSIONS: Our study shows that for patients naive to BV, a single
      dose of SIACI BV after BBBD followed by IV BV offers an encouraging outcome in
      terms of PFS when compared with previous trials using IV BV with and without
      concomitant irinotecan (CPT-11). Larger phase II trials are warranted to
      determine whether repeated IA BV alone is superior to IV BV for recurrent GBM.

PMID- 22405393
TI  - Factors contributing to ventriculostomy infection.
AB  - OBJECTIVE: Catheter-related infection remains a cause of morbidity in the use of
      external ventricular drains (EVDs). The aim of this retrospective single-center
      study was to assess the rate and factors related to ventriculostomy infections in
      the setting of the published literature. METHODS: Patients that underwent EVD
      placement in a single-center were retrospectively reviewed. Diagnosis, treatment,
      hospital course, and infection-related data were collected and analyzed in
      reference to ventriculitis rates. The protocols for EVD placement and maintenance
      were reviewed. RESULTS: Of 343 patients, 12 acquired an EVD infection. No
      significant differences existed between those with and without ventriculitis for
      age, sex, underlying diagnosis, or concomitant systemic infection. Although not
      significant, concomitant systemic infection existed in 4.7% of patients with
      ventriculitis versus 1.5% without. There was a significant difference in length
      of EVD placement in patients with ventriculitis (20.9 +/- 15.3 days) versus those
      without (12.1 +/- 18.2; P = 0.005). Coagulase-negative Staphylococcus and
      Staphylococcus aureus represented the most commonly associated pathogens. With an
      overall cumulative incidence of 3.5%, our rate compared favorably to the
      published literature (cumulative incidence 9.5%; range, 3.9%-23.2%). CONCLUSIONS:
      Catheter-related infection remains an important complication of EVD placement. Of
      factors evaluated, length of time of catheter placement has the most notable
      relationship to infection incidence, suggesting that early drain removal should
      be a goal whenever medically appropriate.

PMID- 22405394
TI  - Management of lumbar spine juxtafacet cysts.
AB  - OBJECTIVE: We review a series of 21 patients with lumbar juxtafacet cysts (LJFCs)
      treated in two institutions. METHODS: The charts of 21 patients with a diagnosis
      of LJFCs during a 6- year period, January 2001 to December 2006, treated at Hamad
      Hospital, Doha, Qatar, and El Ribat University Hospital, Khartoum, Sudan, were
      reviewed. Demographic data, clinical and imaging findings, management, and
      outcome were reviewed. RESULTS: Twenty-one patients with 23 LJFCs were identified
      (14 men, 7 women) with a mean age of 54 years. All presented with back pain and
      radicular symptoms. Ten patients presented with neurogenic claudication due to
      spinal canal stenosis. All had magnetic resonance imaging and dynamic spine
      radiographs. Fourteen LJFCs were found at L4-5 level, 8 at L5-S1 level, and 1 at
      L3-4 level. Three patients had sustained improvement with conservative treatment
      and 17 patients underwent surgical management, mainly through a microsurgical
      approach. Nine of 10 patients with lumbar canal stenosis underwent decompressive
      laminectomy; one patient refused treatment. One patient with bilateral LJFCs and
      mobile spondylolisthesis underwent spinal fusion. All patients, except one, were
      followed up for a period of 12-72 months. CONCLUSIONS: LJFCs may lead to symptoms
      similar to degenerative disc disease. Surgery is reserved for symptomatic
      patients who do not improve satisfactorily with conservative treatment. The
      microsurgical approach is our preferred surgical method and spinal fusion should
      be reserved for patients with spinal instability. Long-term outcome with surgical
      treatment appears satisfactory.

PMID- 22405395
TI  - Ischemic complications after radial artery grafting and aneurysmal trapping for
      ruptured internal carotid artery anterior wall aneurysm.
AB  - OBJECTIVE: Treatment of ruptured internal carotid artery anterior wall (ICAW)
      aneurysms presents a surgical challenge because limitations and difficulties are
      encountered with either clipping or endovascular treatment. The present study
      examined clinical outcomes after aneurysmal trapping followed by radial artery
      grafting for management of these difficult lesions. METHODS: Radial artery
      grafting was followed immediately by parent artery occlusion in five sides of
      five patients with acute ruptured ICAW aneurysm (3 men, 2 women; mean age 55.2
      years). All patients underwent postoperative angiography and computerized
      tomography to assess graft patency and ischemic complications including
      vasospasm. RESULTS: Of the five patients, only one had a poor outcome. However,
      temporary ischemic complications due to vasospasm developed in four (80%) of the
      five patients. Long-term results of radial artery grafting and internal carotid
      trapping for acute stage ruptured ICAW were satisfactory, but detailed analysis
      indicated a high risk of ischemic complications. CONCLUSIONS: The long-term
      result was satisfactory, but there was a high rate of acute stage ischemic
      complications due to delayed vasospasm and low perfusion from the radial artery
      graft. Based on these results, the investigators recommend that, in addition to
      intraoperative anticoagulation therapy, in cases where the cerebral blood flow
      study in the early postoperative period indicates low cerebral perfusion or in
      cases with World Federation of Neurological Societies grade III-V, the patients
      should be placed under the highest level of intensive care to detect ischemic
      complications.

PMID- 22405396
TI  - Aneurysm of a duplicate middle cerebral artery.
AB  - BACKGROUND: Anatomic middle cerebral artery (MCA) anomalies are rare, but each of
      the described variants (eg, duplicate, fenestrated, accessory) can be of clinical
      significance. CASE DESCRIPTION: A 34-year-old man with a history of left
      hemispheric stroke was found to have an aberrant, early-arising duplicate left M1
      segment of the MCA with an associated asymptomatic fusiform aneurysm. The patient
      was treated with a superficial temporal artery (STA) to distal MCA bypass
      followed by surgical trapping of the aneurysm. RESULTS: Intraoperative and follow
      up angiography performed postoperatively at 3 months showed complete isolation of
      the aneurysm from the circulation and patency of the bypass graft. The
      postoperative course was uneventful with the exception of a craniotomy flap
      infection, which was effectively managed with intravenous antibiotics, flap
      removal, and subsequent use of a fabricated replacement. CONCLUSIONS: This rare
      case is presented and used as a framework for a brief discussion of the
      literature regarding both variant MCA anatomy and treatment considerations for
      these anomalies when associated with an aneurysm.

PMID- 22405398
TI  - Percutaneous balloon rhizotomy for trigeminal neuralgia using three-dimensional
      fluoroscopy.
AB  - BACKGROUND: Percutaneous balloon rhizotomy is one of the standard techniques for
      the treatment of trigeminal neuralgia. However, there have been well-reported
      complications from cannulating the foramen ovale (FO). We describe a novel
      technique for cannulating the FO using 3-dimensional (3D) rotational fluoroscopy.
      METHODS: Three-dimensional rotational fluoroscopy is used to reconstruct the
      skull base. The optimal working projection is thus generated to best visualize
      the FO. When the optimal working projection is not anatomically feasible, for
      example, in a patient with severe cervical spondylosis, further rotational
      fluoroscopic data acquisition can assess the position of the needle to determine
      its relationship to the foramen. Furthermore, while inflated, the balloon
      position can also be verified with the same rotational technique. RESULTS: Three
      dimensional rotational fluoroscopy allows quick, safe, and easy cannulation of
      the FO. The equipment is readily available in the biplanar fluoroscopy suite. Its
      use should decrease the incidence of complications reported with the standard
      fluoroscopic technique. CONCLUSIONS: Three-dimensional rotational fluoroscopy
      allows real-time visual guidance to cannulate the FO and determine the optimal
      position of the inflated balloon. We believe that this is an important adjunct
      for treating trigeminal neuralgia via percutaneous techniques.

PMID- 22405397
TI  - Inflammatory pseudotumor of the cerebellum in a patient with Crohn's disease.
AB  - BACKGROUND: Inflammatory pseudotumors are ubiquitous lesions characterized by a
      polymorphous inflammatory infiltrate containing plasma cells and lymphocytes. In
      the central nervous system, this pathological condition is rare and the
      association with Crohn's disease has never been described. CASE DESCRIPTION: A 31
      year-old woman with a history of Crohn's disease was referred to our department
      for progressive headaches and nausea. Neurological examination was normal.
      Magnetic resonance imaging showed an irregular heterogeneous enhanced mass
      infiltrating the left cerebellar hemisphere. Total resection was performed and
      pathological examination led to the conclusion of an inflammatory pseudotumor.
      CONCLUSION: To our knowledge, this case is the first describing an intra-cerebral
      inflammatory pseudotumor associated with an inflammatory bowel disease. The
      diagnosis of an extradigestive location of Crohn's disease was excluded by
      pathological examination. Although the precise cause of this association remains
      unknown, it could be hypothesized that the intra-cranial lesion could be the
      result of the immunosuppressive therapy given for Crohn's disease, or, more
      likely, could be a part of a systemic dysimmune process.

PMID- 22405399
TI  - Extradural en-plaque spinal meningioma with intraneural invasion.
AB  - BACKGROUND: Extradural spinal meningiomas are rare. Our understanding of purely
      extradural spinal meningiomas is incomplete because most reports rarely
      differentiate purely extradural meningiomas from extradural meningiomas with an
      intradural component. Occasionally, reports have described involvement of the
      adjacent nerve root, but there has never been a description of an extradural
      meningioma that actually infiltrates the nerve root. CASE DESCRIPTION: A 42-year
      old woman presented with progressive lower extremity weakness and numbness below
      T3 during the span of 4 months with imaging evidence of an extradural lesion
      compressing the cord from T4 through T6. Surgical resection revealed an
      extradural mass extending through the foramen at T5-6 and encompassing the cord
      and T5 root on the left. Pathologically, the lesion was a World Health
      Organization grade I meningioma with nerve root invasion and a concerning
      elevated mindbomb homolog 1 (MIB-1) of 9.4%. CONCLUSIONS: Purely extradural
      meningiomas are rare, and our case is one of the first to describe a patient with
      an extradural meningioma that actually infiltrates the nerve root. Extradural
      spinal meningiomas are usually not adherent to the dura, but only appear to be
      adherent or invade (as in our patient) the adjacent nerve root. They are easily
      mistaken preoperatively and grossly intraoperatively for malignant metastatic
      tumors and can change the proposed surgical treatment. The long-term prognosis
      remains uncertain, but our patient's last follow-up suggests a favorable
      prognosis.

PMID- 22405400
TI  - Requirements for guidelines systems: implementation challenges and lessons from
      existing software-engineering efforts.
AB  - BACKGROUND: A large body of work in the clinical guidelines field has identified
      requirements for guideline systems, but there are formidable challenges in
      translating such requirements into production-quality systems that can be used in
      routine patient care. Detailed analysis of requirements from an implementation
      perspective can be useful in helping define sub-requirements to the point where
      they are implementable. Further, additional requirements emerge as a result of
      such analysis. During such an analysis, study of examples of existing, software
      engineering efforts in non-biomedical fields can provide useful signposts to the
      implementer of a clinical guideline system. METHODS: In addition to requirements
      described by guideline-system authors, comparative reviews of such systems, and
      publications discussing information needs for guideline systems and clinical
      decision support systems in general, we have incorporated additional requirements
      related to production-system robustness and functionality from publications in
      the business workflow domain, in addition to drawing on our own experience in the
      development of the Proteus guideline system (http://proteme.org). RESULTS: The
      sub-requirements are discussed by conveniently grouping them into the categories
      used by the review of Isern and Moreno 2008. We cite previous work under each
      category and then provide sub-requirements under each category, and provide
      example of similar work in software-engineering efforts that have addressed a
      similar problem in a non-biomedical context. CONCLUSIONS: When analyzing
      requirements from the implementation viewpoint, knowledge of successes and
      failures in related software-engineering efforts can guide implementers in the
      choice of effective design and development strategies.

PMID- 22405401
TI  - Eel osmotic stress transcriptional factor 1 (Ostf1) is highly expressed in gill
      mitochondria-rich cells, where ERK phosphorylated.
AB  - BACKGROUND: Osmotic stress transcriptional factor 1 (Ostf1) was firstly
      identified in tilapia in 2005. Then numerous studies have investigated its
      regulation and expression profile in fish gill tissues in related to
      osmoregulation. Generally, hyperosmotic stress induced ostf1 mRNA expression
      level, however there is no report studying the cellular localization of Ostf1
      expression in any osmoregulatory tissue. In this study immunohistochemical (IHC)
      approach was used to study the cellular localization of Ostf1 in gill cells of
      Japanese eels. FINDINGS: Ostf1 protein was found to be localized in branchial
      mitochondria-rich/chloride cell (MRC/CC) as revealed by Naalpha5 and CFTR co
      localization. The protein was detectable at day 3 after fresh water to seawater
      transfer and was mainly localized in MRCs. Moreover, elevated levels of
      extracellular signal regulated kinase (ERK) phosphorylation was observed at day 3
      of the transfer and was co-localized with MRCs. CONCLUSIONS: Our data identified
      Ostf1 expression in gill MRCs. The observation supports the role of Ostf1 in
      osmosensing and/or osmoregulation in fish gills, particularly its functional
      relationship with MRCs. The observation of the co-expression of pERK and Ostf1 in
      MRCs suggests a cross-talk mechanism between the mitogen-activated protein
      kinases (MAPKs) and Ostf1 in response to hyperosmotic challenge. To summarize,
      this report has addressed the cellular localization of Ostf1 and provides
      evidence to illustrate the involvement of Ostf1 and ERK on osmosensing and
      osmoregulatory function of gill MRCs.

PMID- 22405402
TI  - Interventions to support a palliative care approach in patients with chronic
      obstructive pulmonary disease: an integrative review.
AB  - BACKGROUND: End-stage chronic obstructive pulmonary disease (COPD) is a
      debilitating, life-limiting condition. A palliative approach is appropriate for
      individuals with end-stage COPD, yet currently few interventions embrace this
      holistic, multidisciplinary and inclusive perspective. OBJECTIVE: To describe
      interventions to support a palliative care approach in patients with end-stage
      COPD. DESIGN: Integrative review. DATA SOURCES AND REVIEW METHOD: Peer reviewed
      articles meeting the search criteria were accessed from Medline, PsychINFO,
      CINAHL and Google Scholar databases as well as Caresearch online resource. The
      domains of quality palliative care developed by Steinhauser were used as the
      conceptual framework to synthesise information. RESULTS: This review has shown
      that a range of palliative interventions are used to address the needs of
      individuals with end-stage COPD. Although evidence exists for discrete elements
      of palliative management in this patient group, there is limited evidence for
      health service coordination and models that integrate the multiple domains of
      palliative care with active management. CONCLUSION: Further investigation is
      required to address the complex personal, provider and system elements associated
      with managing end-stage COPD. A comprehensive and collaborative approach is
      required to address the complex and varied needs of individuals with end-stage
      COPD and their families.

PMID- 22405403
TI  - Essential trace element status and clinical outcomes in long-term dialysis
      patients: a two-year prospective observational cohort study.
AB  - BACKGROUND & AIMS: Essential trace elements are involved in many biological
      processes for normal cell function including immunological defense against
      oxidation and infection. Deficiency of these elements generally leads to illness
      or even death in the general population. Therefore, we investigated the
      predictive values of trace element status on clinical outcomes in dialysis
      patients, who are more prone to trace element deficiency. METHODS: We enrolled
      111 prevalent patients on maintenance dialysis from a Taipei tertiary-care
      referral hospital and measured serum levels of selenium, copper, and zinc.
      Patients were followed for 2 years or until death or withdrawal. RESULTS:
      Multivariate Cox regression analysis indicated that patients with diabetes
      mellitus (HR, 2.162 [95% CI, 1.105-4.232], p=0.024), prior stroke (HR, 3.876 [95%
      CI, 1.136-13.221], p=0.030), and zinc deficiency (HR, 0.979 [95% CI, 0.966
      0.992], p=0.002) were more likely to be hospitalized for infectious diseases.
      Furthermore, beyond traditional risk factors, such as old age and
      hypoalbuminemia, multivariate Cox regression also indicated that lower serum
      level of zinc independently predicts overall mortality (HR, 0.973 [95% CI, 0.948
      0.999], p=0.046). CONCLUSIONS: In long-term dialysis patients, the serum level of
      zinc was an independent predictor of future hospitalization due to infectious
      diseases and of overall mortality.

PMID- 22405404
TI  - Time-dependent aroma changes in breast milk after oral intake of a
      pharmacological preparation containing 1,8-cineole.
AB  - BACKGROUND & AIMS: This study investigates time-dependent aroma changes in human
      milk after intake of an odorant-containing pharmaceutical preparation by
      correlating sensory evaluation with quantitative results. METHODS: Human milk
      donors ingested 100 mg of encapsulated 1,8-cineole. 21 milk samples from 12
      participants underwent sensory analysis, of which 14 samples were quantified by
      stable isotope dilution assay (SIDA) analysis. Furthermore, several consecutive
      breast milk and exhaled breath gas samples from one volunteer after intake of 1,8
      cineole were analysed by proton-transfer-reaction mass spectrometry (PTR-MS) and
      sensory evaluation on three separate days. RESULTS: The emergence of the
      characteristic eucalyptus-like odour of 1,8-cineole in exhaled breath after
      capsule ingestion coincided with its transfer into milk; its presence in breath
      was therefore used to indicate the time at which milk should be expressed for
      gathering samples. Odorant transfer could not be confirmed by sensory analysis in
      7 of the 21 milk samples, most likely due to disadvantageous timing of milk
      expression. The other 14 samples exhibited a distinct eucalyptus-like odour.
      Quantitative results matched these observations with <20 MUg/kg 1,8-cineole in
      the odourless samples and 70 to an estimated 2090 MUg/kg 1,8-cineole in the other
      samples. CONCLUSIONS: Transfer of 1,8-cineole into human milk after oral intake
      is time dependent and exhibits large inter and intra-individual differences.

PMID- 22405405
TI  - Diversity of avian haemosporidians in arid zones of northern Venezuela.
AB  - Arid zones of northern Venezuela are represented by isolated areas, important
      from an ornithological and ecological perspective due to the occurrence of
      restricted-range species of birds. We analysed the prevalence and molecular
      diversity of haemosporidian parasites of wild birds in this region by screening
      527 individuals (11 families and 20 species) for parasite mitochondrial DNA. The
      overall prevalence of parasites was 41%, representing 17 mitochondrial lineages:
      7 of Plasmodium and 10 of Haemoproteus. Two parasite lineages occurred in both
      the eastern and western regions infecting a single host species, Mimus gilvus.
      These lineages are also present throughout northern and central Venezuela in a
      variety of arid and mesic habitats. Some lineages found in this study in northern
      Venezuela have also been observed in different localities in the Americas,
      including the West Indies. In spite of the widespread distributions of some of
      the parasite lineages found in northern Venezuela, several, including some that
      are relatively common (e.g. Ven05 and Ven06), have not been reported from
      elsewhere. Additional studies are needed to characterize the host and
      geographical distribution of avian malaria parasite lineages, which will provide
      a better understanding of the influence of landscape, vector abundance and
      diversity, and host identity on haemosporidian parasite diversity and prevalence.

PMID- 22405408
TI  - Women in science.
AB  - To coincide with International Women's Day, Genome Biology asked several female
      scientists about their experience of an academic career, how they managed to
      balance an active research career with family life, and what should be done to
      encourage more women to pursue research careers to stop the 'leaky' pipeline.

PMID- 22405406
TI  - The effect of pegylated interferon-alpha2b and ribavirin combination therapy for
      chronic hepatitis C infection in elderly patients.
AB  - BACKGROUND: The clearance of hepatitis C virus infection by interferon therapy
      significantly reduces the incidence of hepatocellular carcinoma and death in
      elderly chronic hepatitis patients. However, there are few reports concerning the
      efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination
      therapy in elderly patients. The aims of the present study were to examine the
      effect and safety of pegylated interferon-alpha2b plus ribavirin combination
      therapy in 427 patients with chronic hepatitis C infection. We compared the rates
      of sustained virological response--defined as the absence of detectable hepatitis
      C virus in serum 24 weeks after the treatment ended--and the treatment
      discontinuation rate between 319 younger patients aged < 65 years and 108 elderly
      patients aged >= 65 years. We also examined the factors contributing to a
      sustained virological response. RESULTS: There was no significant difference in
      the sustained virological response rate between younger patients and elderly
      patients according to their hepatitis C virus genotype (41.5% (100/241) and 40.7%
      (35/86) for genotype 1; P = 0.899, 89.7% (70/78) and 86.4% (19/22) for genotype
      2; P = 0.703, respectively). There was also no significant difference in the
      treatment discontinuation rate between the two age groups (10.3% (33/319) and
      13.9% (15/108), respectively; P = 0.378). There were no serious adverse events
      requiring hospitalization. The factors contributing significantly to a sustained
      virological response in elderly patients were gender, hepatitis C virus genotype,
      platelet count, and the presence of a rapid or early virological response
      (undetectable hepatitis C virus in serum at weeks 4 or 12 of treatment,
      respectively). However, upon multivariate analysis, the presence of an early
      virological response was the only significant factor (odds ratio: 0.115, 95%
      confidence interval: 0.040- 0.330, P < 0.001). CONCLUSIONS: The efficacy and
      safety of pegylated interferon-alpha2b plus ribavirin combination therapy in
      elderly patients are not always inferior to those in younger patients. Obtaining
      an early virological response may be essential to achieve a sustained virological
      response in elderly patients with chronic hepatitis C infection.

PMID- 22405409
TI  - Leber's optic neuropathy - visual return on alcohol cessation.

PMID- 22405410
TI  - Comparison of the cardiopulmonary parameters after induction of anaesthesia with
      alphaxalone or etomidate in dogs.
AB  - OBJECTIVE: To compare the cardiorespiratory effects and quality of induction of
      and recovery from anaesthesia following etomidate or alphaxalone-HPCD IV. STUDY
      DESIGN: Randomized 'blinded' cross-over study. Twenty-four hours was allowed
      between phases. ANIMALS: Eight healthy adult Beagles (four male, four female).
      METHODS: Dogs were anaesthetized with sevoflurane for instrumentation, then
      allowed to awake. They then received etomidate (treatment E) or alphaxalone-HPCD
      (treatment A) intravenously to effect. Heart rate (HR), body temperature,
      invasive arterial pressures (AP), systemic vascular resistance index (SVRI),
      stroke volume index, cardiac index (CI), contractility, respiratory rate, central
      venous pressure, and capnometry were obtained before anaesthetic induction
      (baseline), 30 seconds and 1 minute after induction, after intubation, one minute
      after intubation, and for every 5 minutes afterwards until the dog began to
      swallow and the trachea was extubated. Arterial bloods were taken for analyses
      before induction, after intubation and every 10 minutes thereafter. The dogs
      breathed room air. The quality of induction of and recovery from anaesthesia were
      scored categorically. Statistical analyses used anova for repeated measures,
      paired t-tests or Wilcoxon signed rank-test as relevant. Significance was set at
      p < 0.05. RESULTS: The induction doses required were (mean +/- SD) 2.91 +/- 0.41
      mg kg(-1) and 4.15 +/- 0.7 mg kg(-1) for treatment E and A respectively. No
      significant changes in cardiovascular parameters were observed with treatment E.
      Treatment A resulted in statistically significant increases in HR and CI and
      reductions of APs and SVRI. Time to extubation was longer with treatment A (25 +/
      7 minutes) than with treatment E (17 +/- 4 minutes). Dogs became hypoxic with
      both treatments. The quality of induction and recovery were excellent with
      treatment A, but significantly less satisfactory with treatment E (recovery
      score, treatment E median 1, range 0-2; treatment A median 0, range 0-1).
      CONCLUSIONS AND CLINICAL RELEVANCE: Alphaxalone-HPCD caused significant
      tachycardia and increase in CI, and statistically (but not clinically)
      significant decreases in APs and SVRI. Etomidate caused no statistically
      significant cardiovascular changes. Quality of recovery was better with
      alfaxalone-HPCD. Both agents caused short-lived hypoxia, and oxygen
      supplementation is advisable.

PMID- 22405411
TI  - Transvaginal posterior colporrhaphy combined with laparoscopic ventral mesh
      rectopexy for isolated Grade III rectocele: a prospective study of 27 patients.
AB  - AIM: The aim of this study was to evaluate prospectively transvaginal posterior
      colporrhaphy (TPC) combined with laparoscopic ventral mesh rectopexy (LVR) in
      patients with a symptomatic isolated rectocele. METHOD: Patients with these
      complaints underwent dynamic and static MRI. All consecutive patients with a
      Grade III (4 cm or more) rectocele and without internal/external rectal prolapse,
      enterocele and external sphincter damage were operated on. The patients completed
      the Obstructed Defecation Syndrome (ODS) score and the Cleveland Clinic
      Incontinence Score (CCIS). All tests were repeated after treatment. Dynamic
      disorders of the pelvic floor detected by MRI were recorded. RESULTS: In 27
      patients [median age 67 (46-73) years], TPC combined with LVR was feasible.
      Complications were limited to port site infection in two patients. Sexual
      discomfort (n = 8) due to prolapse diminished in six (75%) patients and in one
      (4%) de novo dyspareunia developed after treatment. The median follow-up was 12
      (10-18) months. The median CCIS was 12 (10-16) before treatment and 8 (7-10)
      after (P < 0.0001). The median ODS score was 19 (17-23) before and 6 (3-10) after
      treatment (P < 0.0001). There was no change in urinary symptoms. CONCLUSION: TPC
      combined with LVR for obstructed defaecation and faecal incontinence in patients
      with Grade III rectocele significantly relieves the symptoms of these disorders.

PMID- 22405412
TI  - Evidence: making an impact.

PMID- 22405413
TI  - Systematic review of health literacy in Cochrane database studies on paediatric
      asthma educational interventions: searching beyond rigorous design.
AB  - AIM: The purpose of this study was to evaluate if paediatric asthma educational
      intervention studies included in the Cochrane Collaboration database incorporated
      concepts of health literacy. METHODS: Inclusion criteria were established to
      identify review categories in the Cochrane Collaboration database specific to
      paediatric asthma educational interventions. Articles that met the inclusion
      criteria were selected from the Cochrane Collaboration database in 2010. The
      health literacy definition from Healthy People 2010 was used to develop a 4-point
      a priori rating scale to determine the extent a study reported aspects of health
      literacy in the development of an educational intervention for parents and/or
      children. RESULTS: Five Cochrane review categories met the inclusion criteria; 75
      studies were rated for health literacy content regarding educational
      interventions with families and children living with asthma. A priori criteria
      were used for the rating process. While 52 (69%) studies had no information
      pertaining to health literacy, 23 (31%) reported an aspect of health literacy.
      Although all studies maintained the rigorous standards of randomized clinical
      trials, a model of health literacy was not reported regarding the design and
      implementation of interventions. CONCLUSIONS: While a more comprehensive health
      literacy model for the development of educational interventions with families and
      children may have been available after the reviewed studies were conducted,
      general literacy levels still could have been addressed. The findings indicate a
      need to incorporate health literacy in the design of client-centred educational
      interventions and in the selection criteria of relevant Cochrane reviews.
      Inclusion assures that health literacy is as important as randomization and
      statistical analyses in the research design of educational interventions and may
      even assure participation of people with literacy challenges.

PMID- 22405414
TI  - Patients' experiences on donation of their residual biological samples and the
      impact of these experiences on the type of consent given for the future research
      use of the tissue: a systematic review.
AB  - AIM: This review aimed to critically appraise, synthesise and present the best
      available evidence related to the experiences of patients who have donated their
      residual biological samples and the impact of this experience on the type of
      consent given for future research use of these tissues. METHOD: The three-step
      search strategy aimed to find both published and unpublished studies published in
      English between 1990 and 2010 in electronic databases (PubMed, CINAHL, Scopus,
      Embase, PsycINFO, Mednar, PROQUEST). Using the standardised data extraction tool
      from the Joanna Briggs Institute, the Qualitative Assessment and Review
      Instrument, 131 findings were extracted from the 18 papers included in this
      review. These findings generated 19 categories and four synthesised findings.
      RESULTS: The synthesised findings generated were related to the different stages
      of the handling of leftover tissue. The first synthesised finding: patient
      consent to the use of leftover tissue is a complex interaction between many
      factors and not solely driven by perceptions of benefits to self or others,
      relates to the collection of the leftover tissue - the initial consent process.
      The second synthesised finding: healthcare institutions and regulatory
      authorities must provide clear and transparent safeguards and controls, and
      communicate these to the patient prior to the consenting process, outlines the
      issues affecting consent during the processing and storage of the tissues in
      biobanks or research institutions. The third synthesised finding: views on
      ownership and rights to the further use of the leftover tissue varies between
      individual patients and influences their willingness to consent to further use,
      demonstrates the concerns relating to the safeguards on the collection and
      storage of leftover tissue. The fourth synthesised finding: patients have
      opposing views on the use of their leftover tissue for commercial purposes,
      reflecting the differing community beliefs around using leftover tissue for
      research which may provide a commercial benefit to some, but not all, the
      community. CONCLUSION: For leftover tissues to be used, patients must clearly
      understand: the type of consent they are providing (opt in or opt out); the
      parameters for the future research use of their leftover tissues; the safeguards
      put into place to protect the individual and the donated tissue from unethical
      use; and the commercial implications of their consent. IMPLICATIONS FOR PRACTICE:
      This review provides information on patient's experiences on the collection,
      storage, distribution and future use of leftover tissue. These preferences need
      to be understood when designing a prospective model of consent regimen which
      respects patient's confidentiality and wishes. The information in this review is
      especially important for policy-makers designing a prospective model of consent
      regimen for the use of existing and previously collected biological samples with
      no consent taken. IMPLICATIONS FOR RESEARCH: Further research is needed to
      ascertain what factors specifically influence patient's willingness to consent
      for the use of leftover tissue. Factors for further exploration include the
      effects of culture, religion and age. Additionally, further research is required
      to inform the development of specific consent regimes for the use of leftover
      tissue for commercial, stem cell and genetic research.

PMID- 22405415
TI  - Reliability, validity and feasibility of quality of life instruments for adult
      patients with cancer undergoing chemotherapy: result from a systematic review.
AB  - AIM: The aim of this review was to analyse the literature critically and present
      the best available evidence related to quality of life (QoL) instruments that
      consists of all four subscales of physical, psychological, social and spiritual,
      which can be used in the clinical setting to assess adult patients with cancer on
      chemotherapy. INCLUSION CRITERIA: This review included randomised control trials
      and observational studies without control group related to QoL instruments used
      for cancer chemotherapy. The types of participants for this review included all
      adults with cancer over the age of 18 years who have undergone chemotherapy. The
      QoL instruments for this review included instruments that consist of all
      subscales of physical, psychological, social and spiritual. In order to retrieve
      QoL instruments that were current and not outdated, this review included studies
      reported in the recent 10 years. SEARCH STRATEGY: A three-step search strategy
      was utilised to search for primary research articles published in the English
      language from January 1998 to December 2009. An initial search of MEDLINE and
      CINAHL was undertaken followed by analysis of the text words contained in the
      title and abstract, and the text terms used to describe the article. A second
      search strategy using all the identified keywords and the index terms was used
      for the 20 databases. The third search strategy was to search for additional
      studies from the relevant list of all identified articles. METHODOLOGICAL
      QUALITY: The two independent reviewers appraised the included articles for
      methodological quality using the modified Elliot tool for reliability and
      validity. RESULTS: A total of 3149 references was retrieved during the initial
      search. Only 13 articles with validation of the QoL instruments that contained
      all the four subscales of physical, psychological, social and spiritual were
      included in this review. Four QoL instruments were identified. These include the
      City of Hope QOL - Ovarian Cancer Tool (QOL-OVCA), QOL-Breast cancer version (QOL
      BC), New India QoL tool and QoL Index-Cancer version (QLI-CV). Among the four
      identified QoL instruments, the frequency of assessment was more than once for
      QLI-CV, with intervals of 2 weeks to 6 months. Regarding the number of items, the
      QOL-BC instrument has the most number of items. All identified QoL instruments
      have content validity done. For reliability examination, all the identified QoL
      instruments have Cronbach's alpha of 0.7 and above for subscales. The correlation
      between subscales scores and overall QoL score was 0.53-0.93, 0.39-0.95 and 0.65
      0.83 for QOL-OVCA, QOL-BC and QLI-CV, respectively. CONCLUSION: In this review,
      there was one article on development of new QoL instrument, the New India QoL
      tool, which has comprehensive validity examinations - the least number of items
      that may be useful in the clinical setting but need further psychometric testing
      in different settings or languages. The QLI-CV instrument has had comprehensive
      intra- and inter-method validation on different languages, different cultural
      settings and various types of cancer. However, the instrument may not be feasible
      because the method to calculate the QoL score is not straightforward.

PMID- 22405416
TI  - Effects of multidisciplinary models of care for adult pre-dialysis patients with
      chronic kidney disease: a systematic review.
AB  - AIM: To compare the effectiveness of multidisciplinary care with traditional
      medical care on the progression of chronic kidney disease (CKD) in adult pre
      dialysis patients (stages 3-5). METHODS: Eleven databases were searched for
      articles published between January 1990 and July 2009. The Joanna Briggs
      Institute-Meta Analysis of Statistics Assessment and Review Instrument was used
      to assess the methodological quality of retrieved articles and extract data.
      RESULTS: Only four articles out of 927 were included in the systematic review.
      Two reported the results of randomised controlled trials and two reported
      observational studies. The data were not presented in a format that allowed a
      meta-analysis to be performed and therefore a narrative summary of these articles
      is presented. CONCLUSION: Multidisciplinary care is deemed to be effective in
      delaying the progression of CKD in adults who are in the pre-dialysis phase of
      this condition. Education that aims to increase the knowledge and understanding
      of the causes of CKD is an important component of the care. IMPLICATIONS FOR
      PRACTICE: Members of the multidisciplinary team should draw on their specific
      expertise to educate the patient about CKD. The nephrologist or a nurse
      practitioner should devise a management plan jointly with the patient and provide
      regular reviews.

PMID- 22405417
TI  - Quality of maternity care practices of skilled birth attendants in Cambodia.
AB  - BACKGROUND: The World Health Organization's recommended package of interventions
      for the integrated management of pregnancy and childbirth provides guidance for
      the use of evidence-based interventions to ensure the best outcomes for mother
      and newborn. However, the extent to which skilled birth attendants (SBAs) follow
      evidence-based guidelines is not known. There are few studies into childbirth
      practices of SBAs in Cambodia. The aim of this study was to observe practices of
      SBAs during labour, birth and the immediate post-partum period and their
      consistency with evidence-based guidelines. METHODS: A structured non-participant
      observation study was undertaken. Data were collected using an observational
      checklist of evidence-based practices adapted from the Cambodian clinical
      assessment tools for associate degree in midwifery. Maternity care settings in
      one provincial hospital, two district referral hospitals and two health centres
      in one province of Cambodia were purposively selected. RESULTS: Twenty-five SBAs
      who attended 40 women during labour, birth and the postnatal period were
      observed. The results showed that the use of the partograph was low; birth
      companions were not permitted; cleanliness during birth was lacking; management
      of the third stage of labour was inappropriate; monitoring of mother and baby in
      the early postnatal period was lacking; the SBAs lacked skills in neonatal
      resuscitation; skin-to-skin contact with the newborn and early breastfeeding were
      rare; and intramuscular injection of vitamin K varied. CONCLUSION: The findings
      suggest that the current SBA practices during labour, birth and the immediate
      post-partum period in one province of Cambodia are not consistent with evidence
      based guidelines. Service improvements that address evidence-based practices are
      likely to have an impact on clean and safe childbirth, thereby enhancing outcomes
      for Cambodia women.

PMID- 22405418
TI  - Arriba-lib: association of an evidence-based electronic library of decision aids
      with communication and decision-making in patients and primary care physicians.
AB  - AIM: In shared decision-making, patients are empowered to actively ask questions
      and participate in decisions about their healthcare based on their preferences
      and values. Decision aids should help patients make informed choices among
      diagnostic or treatment options by delivering evidence-based information on
      options and outcomes; however, they have rarely been field tested, especially in
      the primary care context. We therefore evaluated associations between the use of
      an interactive, transactional and evidence-based library of decision aids (arriba
      lib) and communication and decision-making in patients and physicians in the
      primary care context. METHODS: Our electronic library of decision aids ('arriba
      lib') includes evidence-based modules for cardiovascular prevention, diabetes,
      coronary heart disease, atrial fibrillation and depression. Twenty-nine primary
      care physicians recruited 192 patients. We used questionnaires to ask patients
      and physicians about their experiences with and attitudes towards the programme.
      Patients were interviewed via telephone 2 months after the consultation. Data
      were analysed by general estimation equations, cross tab analyses and by using
      effect sizes. RESULTS: Only a minority (8.9%) of the consultations were felt to
      be too long because physicians said consultations were unacceptably extended by
      arriba-lib. We found a negative association between the detailedness of the
      discussion of the clinical problem's definition and the age of the patients.
      Physicians discuss therapeutic options in less detail with patients who have a
      formal education of less than 8 years. Patients who were counselled by a
      physician with no experience in using a decision aid more often reported that
      they do not remember being counselled with the help of a decision aid or do not
      wish to be counselled again with a decision aid. CONCLUSIONS: Arriba-lib has
      positive associations to the decision-making process in patients and physicians.
      It can also be used with older age groups and patients with less formal
      education. Physicians seem to adapt their counselling strategy to different
      patient groups. Prior experience with the use of decision aids has an influence
      on the acceptance of arriba-lib in patients but not on their decision-making or
      decision implementation.

PMID- 22405419
TI  - Graduated compression stockings for the prevention of postoperative venous
      thromboembolism in obstetric patients: a best practice implementation project.
AB  - AIMS: The aims of this project were twofold: to compare our current venous
      thromboembolism management in postoperative Caesarean section patients with the
      current best evidence on the use of graduated compression stockings and to
      standardise mechanical venous thromboembolism prophylaxis guidelines where
      multiple approaches had previously been used. METHOD: Thirty post-Caesarean
      section patients from a private hospital in Perth, Western Australia, were
      audited in a three-phase project: (i) the initial audit; (ii) clinical practice
      change including greater venous thromboembolism awareness and targeted education
      for midwives, standardised guidelines for mechanical prophylaxis, the development
      of an online venous thromboembolism module, a venous thromboembolism prophylaxis
      policy and heightened consumer involvement; and (iii) a follow-up audit. RESULTS:
      Our initial audit result demonstrated opportunities for improvement across all
      audit criteria. The interventions were undertaken over a 3-month period from
      August to October 2010. The follow-up audit results showed pleasing improvements
      across four audit criteria with one criterion unchanged. CONCLUSION: While the
      follow-up audit showed significant clinical improvements, the tight time frame
      for the development and implementation of multiple interventions created major
      challenges. We believe that given time to embed these changes, further
      improvements will be seen. Ongoing audits will be conducted to ensure the
      sustainability of these changes. The change in practice and subsequent
      improvements demonstrated at this private hospital provide evidence to encourage
      other midwifery units to pursue best practice in the management of this high-risk
      patient cohort.

PMID- 22405423
TI  - [Treatment plans for cleft lip and palate in Russia].

PMID- 22405424
TI  - The first reported generation of several induced pluripotent stem cell lines from
      homozygous and heterozygous Huntington's disease patients demonstrates mutation
      related enhanced lysosomal activity.
AB  - Neuronal disorders, like Huntington's disease (HD), are difficult to study, due
      to limited cell accessibility, late onset manifestations, and low availability of
      material. The establishment of an in vitro model that recapitulates features of
      the disease may help understanding the cellular and molecular events that trigger
      disease manifestations. Here, we describe the generation and characterization of
      a series of induced pluripotent stem (iPS) cells derived from patients with HD,
      including two rare homozygous genotypes and one heterozygous genotype. We used
      lentiviral technology to transfer key genes for inducing reprogramming. To
      confirm pluripotency and differentiation of iPS cells, we used PCR amplification
      and immunocytochemistry to measure the expression of marker genes in embryoid
      bodies and neurons. We also analyzed teratomas that formed in iPS cell-injected
      mice. We found that the length of the pathological CAG repeat did not increase
      during reprogramming, after long term growth in vitro, and after differentiation
      into neurons. In addition, we observed no differences between normal and mutant
      genotypes in reprogramming, growth rate, caspase activation or neuronal
      differentiation. However, we observed a significant increase in lysosomal
      activity in HD-iPS cells compared to control iPS cells, both during self-renewal
      and in iPS-derived neurons. In conclusion, we have established stable HD-iPS cell
      lines that can be used for investigating disease mechanisms that underlie HD. The
      CAG stability and lysosomal activity represent novel observations in HD-iPS
      cells. In the future, these cells may provide the basis for a powerful platform
      for drug screening and target identification in HD.

PMID- 22405425
TI  - Pneumatosis intestinalis and portal venous gas secondary to Gefitinib therapy for
      lung adenocarcinoma.
AB  - BACKGROUND: Pneumatosis intestinalis (PI), defined as the presence of gas in the
      bowel wall, and portal venous gas (PVG) are relatively rare radiological
      findings. Although several chemotherapeutic agents and anti-vascular endothelial
      growth factor agents are reported to be associated with PI and PVG, an
      association with anti-epidermal growth factor receptor (EGFR) agents has not been
      described previously. CASE PRESENTATION: The present report describes a case of
      PI and PVG secondary to treatment with an EGFR tyrosine kinase inhibitor. A 66
      year-old woman who had been diagnosed with metastatic lung adenocarcinoma
      presented with nausea, vomiting and abdominal distension after commencing
      gefitinib. A computed tomography (CT) scan of the abdomen revealed PI extending
      from the ascending colon to the rectum, hepatic PVG, and infarction of the liver.
      Gefitinib therapy was discontinued immediately and the patient was managed
      conservatively. A follow-up CT scan 2 weeks later revealed that the PI and
      hepatic PVG had completely resolved. CONCLUSION: This is the first report of PI
      and PVG caused by EGFR tyrosine kinase inhibitor. Although these complications
      are extremely rare, clinicians should be aware of the risk of PI and PVG in
      patients undergoing targeted molecular therapy.

PMID- 22405426
TI  - Hypertrophy and senescence factors in yeast aging. A reply to Bilinski et al.

PMID- 22405427
TI  - Focused magnetic stem cell targeting to the retina using superparamagnetic iron
      oxide nanoparticles.
AB  - Developing new ways of delivering cells to diseased tissue will be a key factor
      in translating cell therapeutics research into clinical use. Magnetically
      targeting cells enables delivery of significant numbers of cells to key areas of
      specific organs. To demonstrate feasibility in neurological  tissue, we targeted
      cells magnetically to the upper hemisphere of the rodent retina. Rat mesenchymal
      stem cells (MSCs) were magnetized using superparamagnetic iron oxide
      nanoparticles (SPIONs). In vitro studies suggested that magnetization with
      fluidMAG-D was well tolerated, that cells remained  viable, and they retained
      their differentiation capabilities. FluidMAG-D-labeled MSCs were injected
      intravitreally or via the tail vein of the S334ter-4 transgenic rat model of
      retinal degeneration with or without placing a gold-plated neodymium disc magnet
      within the orbit, but outside the  eye. Retinal flatmount and cryosection imaging
      demonstrated that after intravitreal injection cells localized to the inner
      retina in a tightly confined area corresponding to the position of the orbital
      magnet. After intravenous injection, similar retinal localization was achieved
      and remarkably  was associated with a tenfold increase in magnetic MSC delivery
      to the retina. Cryosections demonstrated that cells had migrated into both the
      inner and outer retina. Magnetic MSC treatment with orbital magnet also resulted
      in significantly higher retinal concentrations of anti-inflammatory  molecules
      interleukin-10 and hepatocyte growth factor. This suggested that intravenous MSC
      therapy also resulted in significant therapeutic benefit in the dystrophic
      retina. With minimal risk of collateral damage, these results suggest that
      magnetic cell delivery is the best approach for controlled  delivery of cells to
      the outer retina-the focus for disease in age-related macular degeneration and
      retinitis pigmentosa.

PMID- 22405428
TI  - Palliative surgery in the do-not-resuscitate patient: ethics and practical
      suggestions for management.
AB  - Palliative care in the United States has made tremendous strides in the last
      decade. One of the most perplexing issues arises when a palliative care patient
      presents to the operating room with an already existing do-not-resuscitate (DNR)
      order. This article describes the most common conflicting issues that may arise
      and provides guidance to surgeons, anesthesiologists, patients, and their primary
      physicians to reach satisfactory resolution and optimal care. Anesthesia
      departments should appoint a liaison to surgical and perioperative nursing
      departments to provide education and create an atmosphere conducive to
      discussions with palliative care patients about goals of care, including DNR
      status.

PMID- 22405429
TI  - Surgical palliative care: recent trends and developments.
AB  - Palliation has been an essential, if not the primary, activity of surgery during
      much of its history. However, it has been only during the past decade that the
      modern principles and practices of palliative care developed in the nonsurgical
      specialties in the United States and abroad have been introduced to surgical
      institutions, widely varied practice settings, education, and research.

PMID- 22405430
TI  - Palliative medicine in the surgical intensive care unit and trauma.
AB  - The purpose of palliative medicine is to prevent and relieve suffering and to
      help patients and their families set informed goals of care and treatment.
      Palliative medicine can be provided along with life-prolonging treatment or as
      the main focus of treatment. Increasingly, palliative medicine has a role in the
      surgical intensive care unit (SICU) and trauma. Data show involving palliative
      medicine in the SICU results in decreased length of stay, improved communication
      with families and patients, and earlier setting of goals of care, without
      increasing mortality. The use of triggers for palliative medicine consultation
      improves patient-centered care in the SICU.

PMID- 22405431
TI  - Care of the family in the surgical intensive care unit.
AB  - In the surgical intensive care unit (SICU), the stress of having a critically ill
      loved one creates significant bereavement and emotional needs for family members.
      Surgical palliative care has expanded; clinicians do not just treat the patient,
      but now include the family within the scope of care. Understanding and treating
      complicated grief, and the emotional and educational needs of the family improves
      family outcome, improves the surrogate family's ability to act as decision
      makers, and ultimately may positively affect patient survivor outcome. Care of
      families in the SICU requires interdisciplinary teams and palliative care
      processes to appropriately address their needs.

PMID- 22405432
TI  - Communication as a core skill of palliative surgical care.
AB  - Excellence as a surgeon requires not only the technical and intellectual ability
      to effectively take care of surgical disease but also an ability to respond to
      the needs and questions of patients. This article provides an overview of the
      importance of communication skills in optimal surgical palliation and offers
      suggestions for a multidisciplinary team approach, using the palliative triangle
      as the ideal model of communication and interpersonal skills. This article also
      discusses guidelines for advanced surgical decision making and outlines methods
      to improve communication skills.

PMID- 22405433
TI  - Surgical palliative care in Haiti.
AB  - Palliative care in itself has many challenges; these challenges are compounded
      exponentially when placed in the setting of a mass casualty event, such as the
      2010 Haiti earthquake. Haiti itself was an austere environment with very little
      infrastructure before the disaster. US surgeons, intensivists, and nurses worked
      hand in hand with other international providers and Haitian volunteers to provide
      the best care for the many. Improvisation and teamwork as well as respect for the
      Haitian caregivers were crucial to their successes. Sisyphean trials lie ahead.
      Haiti and its people must not be forgotten.

PMID- 22405434
TI  - Paravertebral blocks.
AB  - Paravertebral blocks have been demonstrated to represent an interesting
      alternative to epidural, especially for the management of perioperative and
      trauma pain. Initially performed mostly as single-shot blocks for breast surgery,
      thoracotomy, and hernia repairs in adults and children, presently these blocks
      are also used for placement of a paravertebral catheter, either unilateral or
      bilateral. Although complications associated with the performance of these blocks
      are infrequent, the use of ultrasound-guided approaches, which allow performing
      the block under direct vision, is becoming the standard in most groups performing
      these blocks routinely.

PMID- 22405435
TI  - Recent advances in multimodal analgesia.
AB  - Greater understanding of the pathophysiology and mechanism of acute pain has led
      to advances in pharmacologic therapy. Understanding the principles of multimodal
      therapy along with surgical-specific protocols leads to improved outcome in
      patients. However, further large-scale randomized trials need to be performed to
      further establish and demonstrate the long-term benefit of multimodal therapy for
      patients undergoing surgery.

PMID- 22405436
TI  - Pediatric pain management.
AB  - Regional anesthesia has become an integral part of adult anesthesia. Although not
      routinely used in children because of the need for general anesthesia that is
      necessary to keep the patients from moving and cooperating with the operator,
      regional anesthesia has been gaining immense popularity in the last decade.
      Although there is not much objective evidence, large prospective databases and
      expert opinion have favored administering regional anesthesia in the asleep child
      safely because major neural damage has not been reported in children. This review
      discusses a comprehensive approach to acute pain management in infants, children,
      and adolescents using regional anesthesia.

PMID- 22405437
TI  - Surgical palliative care and pain management. Foreword.

PMID- 22405438
TI  - Update on surgical palliative care.

PMID- 22405439
TI  - A survey tool for measuring evidence-based decision making capacity in public
      health agencies.
AB  - BACKGROUND: While increasing attention is placed on using evidence-based decision
      making (EBDM) to improve public health, there is little research assessing the
      current EBDM capacity of the public health workforce. Public health agencies
      serve a wide range of populations with varying levels of resources. Our survey
      tool allows an individual agency to collect data that reflects its unique
      workforce. METHODS: Health department leaders and academic researchers
      collaboratively developed and conducted cross-sectional surveys in Kansas and
      Mississippi (USA) to assess EBDM capacity. Surveys were delivered to state- and
      local-level practitioners and community partners working in chronic disease
      control and prevention. The core component of the surveys was adopted from a
      previously tested instrument and measured gaps (importance versus availability)
      in competencies for EBDM in chronic disease. Other survey questions addressed
      expectations and incentives for using EBDM, self-efficacy in three EBDM skills,
      and estimates of EBDM within the agency. RESULTS: In both states, participants
      identified communication with policymakers, use of economic evaluation, and
      translation of research to practice as top competency gaps. Self-efficacy in
      developing evidence-based chronic disease control programs was lower than in
      finding or using data. Public health practitioners estimated that approximately
      two-thirds of programs in their agency were evidence-based. Mississippi
      participants indicated that health department leaders' expectations for the use
      of EBDM was approximately twice that of co-workers' expectations and that the use
      of EBDM could be increased with training and leadership prioritization.
      CONCLUSIONS: The assessment of EBDM capacity in Kansas and Mississippi built upon
      previous nationwide findings to identify top gaps in core competencies for EBDM
      in chronic disease and to estimate a percentage of programs in U.S. health
      departments that are evidence-based. The survey can serve as a valuable tool for
      other health departments and non-governmental organizations to assess EBDM
      capacity within their own workforce and to assist in the identification of
      approaches that will enhance the uptake of EBDM processes in public health
      programming and policymaking. Localized survey findings can provide direction for
      focusing workforce training programs and can indicate the types of incentives and
      policies that could affect the culture of EBDM in the workplace.

PMID- 22405440
TI  - Phylogenetic reconstruction of dengue virus type 2 in Colombia.
AB  - BACKGROUND: Dengue fever is perhaps the most important viral re-emergent disease
      especially in tropical and sub-tropical countries, affecting about 50 million
      people around the world yearly. In Colombia, dengue virus was first detected in
      1971 and still remains as a major public health issue. Although four viral
      serotypes have been recurrently identified, dengue virus type 2 (DENV-2) has been
      involved in the most important outbreaks during the last 20 years, including 2010
      when the fatality rate highly increased. As there are no major studies reviewing
      virus origin and genotype distribution in this country, the present study
      attempts to reconstruct the phylogenetic history of DENV-2 using a sequence
      analysis from a 224 bp PCR-amplified product corresponding to the carboxyl
      terminus of the envelope (E) gene from 48 Colombian isolates. RESULTS: As
      expected, the oldest isolates belonged to the American genotype (subtype V), but
      the strains collected since 1990 represent the American/Asian genotype (subtype
      IIIb) as previously reported in different American countries. Interestingly, the
      introduction of this genotype coincides with the first report of dengue
      hemorrhagic fever in Colombia at the end of 1989 and the increase of cases during
      the next years. CONCLUSION: After replacement of the American genotype, several
      lineages of American/Asian subtype have rapidly spread all over the country
      evolving in new clades. Nevertheless, the direct association of these new
      variants in the raise of lethality rate observed during the last outbreak has to
      be demonstrated.

PMID- 22405441
TI  - Lack of association between connexin40 polymorphisms and coronary artery disease.
AB  - OBJECTIVE: Cx40 is a gap junction protein important for cell-cell communication
      in the endothelium. Polymorphisms in the promoter region of the human Cx40 gene, 
      44G>A and +71A>G, were shown to reduce Cx40 transcription by half. As mice with
      an endothelial-specific deletion of Cx40 are more susceptible to atherosclerosis,
      this study was designed to discover a correlation between these polymorphisms and
      atherosclerosis in European populations. METHODS AND RESULTS: 803 patients
      referred to the Geneva University Hospitals for elective coronary angiography
      were divided according to the number of significantly stenosed vessels (from 0 to
      3) and were genotyped for the Cx40 polymorphisms. Genotype distribution in the
      control group was -44GG/+71AA=59.8%, -44AG/+71AG=35.1% and -44AA/+71GG=5.2%.
      Surprisingly, this distribution was similar in the CAD group, with 
      44GG/+71AA=58.5%, -44AG/+71AG=37.6% and -44AA/+71GG=3.8% (p=0.67). Moreover, no
      significant association between histological carotid plaque composition of
      culprit lesions and Cx40 polymorphisms could be detected in 583 Dutch patients of
      the Athero-Express study. CONCLUSIONS: Despite a clear antiatherogenic role of
      Cx40 in mice, our study could not detect an association of Cx40 promoter
      polymorphisms and CAD in human. Moreover, a correlation with atherosclerotic
      plaque stability or hypertension could not be demonstrated either. Connexin
      polymorphisms affecting channel function may be of greater importance for
      cardiovascular disease than polymorphisms affecting the expression level of the
      protein.

PMID- 22405442
TI  - High-sensitive Troponin I in acute cardiac conditions: implications of baseline
      and sequential measurements for diagnosis of myocardial infarction.
AB  - BACKGROUND: High-sensitive Troponin I (hsTnI) facilitates the early diagnosis of
      myocardial infarction (MI). However, since hsTnI has not been well characterized
      in non-ischemic cardiac conditions, the predictive value of hsTnI for MI remains
      unclear. METHODS: hsTnI (ADVIA Centaur, Siemens) on admission was analyzed in 929
      patients with acute cardiac condition and invasive ascertainment of coronary
      status by catheterization. RESULTS: Hs-TnI upon presentation was higher in
      patients with STEMI (median 1.27 ng/mL, IQR 0.13-14.5 ng/mL) as compared to
      patients with Non-STEMI (0.66 ng/mL, IQR 0.10-4.0 ng/mL, p<0.001) whereas it did
      not differ from STEMI in Tako-Tsubo cardiomyopathy (2.57 ng/mL, IQR 0.17-8.4
      ng/mL) and myocarditis (9.76 ng/mL, IQR 2.0-27.0 ng/mL). In patients with
      resuscitation of non-ischemic cause (0.31 ng/mL, IQR 0.06-1.3 ng/mL), acute heart
      failure (0.088 ng/mL, IQR 0.035-0.30 ng/mL) and hypertensive emergency (0.066
      ng/mL, IQR 0.032-0.34 ng/mL), hs-TnI was elevated above the recommended threshold
      of 0.04 ng/mL. At this cutpoint of 0.04 ng/mL, hsTnI indicated acute MI (STEMI or
      Non-STEMI) with a sensitivity of 88% and a specificity of 45% (ROC-AUC 0.748).
      When patients with STEMI were excluded, hsTnI indicated Non-STEMI with a
      sensitivity of 87% and a specificity of 45% (ROC-AUC 0.725). When sequential
      measurements were taken into account in a restricted cohort, a maximum hsTnI of
      >=0.40 ng/mL provided a sensitivity of 89% and a specificity of 85% (ROC-AUC
      0.909) for Non-STEMI. CONCLUSIONS: HsTnI is a sensitive, albeit unspecific marker
      of MI. In patients with mildly elevated hsTnI and without evidence for STEMI, we
      suggest serial assessment of hsTnI and a 10-fold higher cutpoint of 0.40 ng/mL
      before Non-STEMI is assumed.

PMID- 22405443
TI  - Physical restraints versus seclusion room for management of people with acute
      aggression or agitation due to psychotic illness (TREC-SAVE): a randomized trial.
AB  - BACKGROUND: After de-escalation techniques have failed, restraints, seclusion
      and/or rapid tranquillization may be used for people whose aggression is due to
      psychosis. Most coercive acts of health care have not been evaluated in trials.
      METHOD: People admitted to the emergency room of Instituto Philippe Pinel, Rio de
      Janeiro, Brazil, whose aggression/agitation was thought due to psychosis and for
      whom staff were unsure if best to restrict using physical restraints or a
      seclusion room, were randomly allocated to one or the other and followed up to 14
      days. The primary outcomes were 'no need to change intervention early - within 1
      h' and 'not restricted by 4 h'. RESULTS: A total of 105 people were randomized.
      Two-thirds of the people secluded were able to be fully managed in this way. Even
      taking into account the move out of seclusion into restraints, this study
      provides evidence that embarking on the less restrictive care pathway (seclusion)
      does not increase overall time in restriction of some sort [not restricted by 4
      h: relative risk 1.09, 95% confidence interval 0.75-1.58; mean time to release:
      restraints 337.6 (s.d.=298.2) min, seclusion room 316.3 (s.d.=264.5) min,
      p=0.48]. Participants tended to be more satisfied with their care in the
      seclusion group (17.0% v. 11.1%) but this did not reach conventional levels of
      statistical significance (p=0.42). CONCLUSIONS: This study should be replicated,
      but suggests that opting for the least restrictive option in circumstances where
      there is clinical doubt does not harm or prolong coercion.

PMID- 22405444
TI  - Differences in mating behavior lead to asymmetric mating interactions and
      consequential changes in sex ratio between an invasive and an indigenous
      whitefly.
AB  - The invasive B whitefly and the indigenous ZHJ2 whitefly in China of the Bemisia
      tabaci complex represent two previously allopatric cryptic species. Laboratory
      experiments have shown that the invasive B can displace the indigenous ZHJ2.
      Here, we observed the mating behavior and mating interactions between B and ZHJ2
      to elucidate the behavioral mechanisms underlying their competition. The 2
      species are able to mate with each other, although at a significantly lower
      frequency than that between males and females within the same species.
      Heterospecifically-mated females produce only male progeny, indicating
      reproductive isolation. Heterospecific mating had only a marginal effect on
      reproduction of females in either species. Detailed observations on mating
      interactions between the 2 species showed that B had higher sexual activity than
      ZHJ2. B males were more likely to interrupt courtships initiated by rival males
      than ZHJ2 males. Compared with ZHJ2 males, B males were also more likely to
      successfully interrupt courtships initiated by rival heterospecific males than by
      males of the same species. In addition, B males guarded B females post
      copulation, whereas ZHJ2 males did not. When the 2 species co-occurred, the
      behavioral differences and interactions between them resulted in an increased
      proportion of females produced in the offspring of B but reduced proportion of
      females in the progeny of ZHJ2. These asymmetric mating interactions might be an
      important mechanism underlying the displacement of ZHJ2 by B. Our study shows
      that reproductive interference might contribute to the competitive exclusion
      between closely related species during biological invasions.

PMID- 22405445
TI  - Effects of disturbance on small mammal community structure in the New Jersey
      Pinelands, USA.
AB  - We compared small mammal community composition among undisturbed habitats and
      habitats disturbed by military operations on Warren Grove Gunnery Range (WGR) in
      the New Jersey Pinelands. WGR is one of the largest tracts of protected land
      within this globally rare ecosystem. Disturbance in the form of fire, mowing,
      soil disruption and logging has had a large effect on small mammal occurrence and
      distribution. Of the 14 small mammal species that occur in the Pinelands, 9 live
      on WGR, including large populations of the southern bog lemming (Synaptomys
      cooperi Baird, 1858) and meadow jumping mouse [Zapus hudsonius (Zimmermann,
      1780)]. Simpson's Index of Diversity was 0 for most disturbed sites and was
      generally greater in wetlands than in uplands. White-footed mouse [Peromyscus
      leucopus (Rafinesque, 1818)] was the most common species on WGR and had a
      dominant effect on species diversity and community similarity indices. It
      dominated upland habitats and was the only species to occur in several disturbed
      habitats, whereas all 9 species occurred in wetlands. Principal components
      analysis indicated that most variation in species diversity was explained by
      disturbance and differences between upland and wetland habitats, due to presence
      of white-footed mice in disturbed and upland sites. Meadow jumping mice, southern
      bog lemmings and red-back voles [Myodes gapperi (Vigors, 1830)] were positively
      correlated with wetland habitats, and pine voles [Microtus pinetorum (Le Conte,
      1830)], short-tail shrews [Blarina brevicauda (Say, 1823)] and eastern chipmunks
      [Tamias striatus (Linnaeus, 1758)] were associated with uplands. Habitat
      heterogeneity at WGR, including extensive undisturbed wetlands and uplands
      supported a rich diversity of small mammal species.

PMID- 22405446
TI  - Spatial and temporal effects on seed dispersal and seed predation of Musa
      acuminata in southern Yunnan, China.
AB  - Wild bananas are abundant in tropical areas and many ecologists have observed
      that the succession process is quicker following increased disturbance. This
      study was conducted to analyze animal-seed interactions and their effects on the
      seed fate of a wild banana species (Musa acuminata) in tropical southern Yunnan
      (China) through experiments considering spatial (site and habitat) and temporal
      (seasons) variation. The largest proportion of fruits (81%) was removed by
      frugivorous seed dispersers, especially by bats at nighttime. Only 13% of the
      fruits were removed by climbing seed predators (different species of rats). In
      the exclosure treatment, rodents accounted for a significantly higher total
      artificially exposed seed removal number than ants, but with spatial and temporal
      differences. The highest seed predation rate by rodents (70%) was found in forest
      with wild banana stands, corresponding with the highest rodent diversity (species
      numbers and abundance) among the habitat types. In contrast, the seed removal
      number by ants (57%) was highest in the open land habitats, but there was no
      close correlation with ant diversity. Seed removal numbers by ants were
      significantly higher in the dry compared to the rainy season, but rodent activity
      showed no differences between seasons. The overall results suggest that the
      largest proportion of seeds produced by wild banana are primarily dispersed by
      bats. Primary seed dispersal by bats at nighttime is essential for wild banana
      seeds to escape seed predation.

PMID- 22405447
TI  - Relative abundance of American badger (Taxidea taxus) and red fox (Vulpes vulpes)
      in landscapes with high and low rodenticide poisoning levels.
AB  - Over the past decade, extensive poisoning campaigns have been conducted in
      southern Saskatchewan to control Richardson's ground squirrel Spermophilus
      richardsonii (Sabine, 1822) populations. Such campaigns might impact on predator
      abundance by decreasing prey levels, and also through secondary poisoning. Using
      spotlighting, we investigated the relative abundance of American badgers Taxidea
      taxus (Schreber, 1777) and red fox Vulpes vulpes (Linnaeus, 1758) in 2 study
      areas with road access and crops, but with different levels of poisoning. In the
      study area with relatively low poisoning (19.6% of the area traversed by roads),
      there were 2.2 times more American badgers per km of road and 6.4 times more red
      foxes per km than in the study area with high poisoning (89.7% of the area). It
      is recommended that an Integrated Pest Management program be developed to
      conserve natural predators across landscapes.

PMID- 22405448
TI  - Wound healing during hibernation by black bears (Ursus americanus) in the wild:
      elicitation of reduced scar formation.
AB  - Even mildly hypothermic body or limb temperatures can retard healing processes in
      mammals. Despite this, we observed that hibernating American black bears (Ursus
      americanus Pallas, 1780) elicit profound abilities in mounting inflammatory
      responses to infection and/or foreign bodies. In addition, they resolve injuries
      during hibernation while maintaining mildly hypothermic states (30-35  degrees C)
      and without eating, drinking, urinating or defecating. We describe experimental
      studies on free-ranging bears that document their abilities to completely resolve
      cutaneous cuts and punctures incurred during or prior to hibernation. We induced
      small, full-thickness cutaneous wounds (biopsies or incisions) during early
      denning, and re-biopsied sites 2-3 months later (near the end of denning).
      Routine histological methods were used to characterize these skin samples. All
      biopsied sites with respect to secondary intention (open circular biopsies) and
      primary intention (sutured sites) healed, with evidence of initial eschar (scab)
      formation, completeness of healed epidermis and dermal layers, dyskeratosis
      (inclusion cysts), and abilities to produce hair follicles. These healing
      abilities of hibernating black bears are a clear survival advantage to animals
      injured before or during denning. Bears are known to have elevated levels of
      hibernation induction trigger (delta-opioid receptor agonist) and ursodeoxycholic
      acid (major bile acid within plasma, mostly conjugated with taurine) during
      hibernation, which may relate to these wound-healing abilities. Further research
      as to the underlying mechanisms of wound healing during hibernation could have
      applications in human medicine. Unique approaches may be found to improve healing
      for malnourished, hypothermic, diabetic and elderly patients or to reduce
      scarring associated with burns and traumatic injuries.

PMID- 22405449
TI  - Sea urchin coelomocyte arylsulfatase: a modulator of the echinoderm clotting
      pathway.
AB  - Sea urchin petalloid coelomocytes effectuate the clotting pathway by undergoing a
      rapid and dynamic cellular transformation that leads to cellular adhesion and
      wounds closure. We have identified high levels of activity of arylsulfatase (Ars)
      associated with coelomocytes of the sea urchin Lytechinus variegatus (Lamarck,
      1816). Ars activity was extracted from clotted coelomocytes with EDTA and showed
      high levels of activity up to a 1:100 dilution. Clot formation from isolated
      coelomic fluid was significantly inhibited by the ARS inhibitor, p-nitrophenyl
      phosphate. Ars activity was collected by 80% ethanol precipitation, a diagnostic
      test previously used in Ars isolation. Cellular extraction studies in the
      presence and absence of the non-ionic detergent Triton X-100 indicated that some
      Ars activity was present intracellularly, possibly in intracellular membrane
      bound compartments, however the majority of Ars activity was extracted from the
      extracellular coelomocyte membrane. Polyclonal anti-sea urchin embryo Ars
      antibodies recognized a single protein band with an approximate molecular weight
      of 75 kDa on western blots. Immunofluorescence using the anti-sea urchin Ars
      antibody revealed an intracellular and extracellular staining of Ars in both
      petalloid and filopodial coelomocytes. Taken together, these data indicate that
      coelomocyte Ars might be involved in cell-to-cell crosslinking of surface
      sulfated polysaccharides vital for clot formation.

PMID- 22405450
TI  - Use of electrosense in the feeding behavior of sturgeons.
AB  - The electro-receptive lateral line system appeared early in the evolutionary
      history of fish. Sturgeons, members of the primitive Chondrostei group, are known
      for their electroreceptors (ampullae of Lorenzini) on the head, which are thought
      to be sensitive to weak electric fields in aquatic environments and involved in
      feeding, mating and migration. Here, we report the results of a set of behavioral
      and electrophysiological experiments designed to determine the function and
      characteristics of the electrosense in cultured sturgeons. The results showed
      Siberian sturgeon (Acipenser baerii Brandt, 1869) feeding striking at bio
      electric fields produced by living feed-fish enclosed in a gel chamber and at the
      corrosion field produced by metal rods. With an electric stimulus that mimics the
      bio-electric fields produced by living prey, the relative discharge rate of
      electrosensory neurons in the dorsal octavolateralis nucleus (DON) was modulated
      by and phase-locked to sinusoidal stimulus and some units showed selectivity for
      dipolar direction in white sturgeon (Acipenser transmontanus Richardson, 1836).
      This is the first study to provide the empirical evidence correlating with
      electrosensory behaviors and electrophysiological responses in cultured
      sturgeons, and suggesting that electrosense does play an innate role in feeding
      behavior of sturgeon. We believe this will have important implications for
      protecting sturgeons in the wild.

PMID- 22405451
TI  - Morphological structure and peripheral innervation of the lateral line system in
      the Siberian sturgeon (Acipenser baerii).
AB  - Light and scanning electron microscopy (SEM) were used to study the epidermal
      lateral line system of the Siberian sturgeon (Acipenser baerii Brandt, 1869).
      This system consists of mechanoreceptive neuromasts, ampullae and the
      electroreceptive organ. The neuromasts are located in 5 pairs of cephalic and 1
      pair of trunk canals and superficially in the middle and posterior pit lines that
      lie dorsomedially along the top of the skull immediately adjacent to the otic
      ampullae field. Both canal neuromasts and pit organ superficial neuromasts have
      opposite polarized hair cells that are parallel along the axis of the canal and
      pit line, respectively. However, they differ in both size and shape and in the
      density and length of the hair bundles. The ampullae are confined on the head,
      adjacent to the neuromast lines. The morphological structure of the ampullae in
      the Siberian sturgeon is similar to the ampullae in elasmobranchs and other
      primitive fish. Nevertheless, it has a relatively large mucus-filled ampulla, and
      a shorter and narrower canal leading to a small opening to the outer epidermal
      surface. We also present new information concerning the peripheral innervation of
      lateral line receptors in sturgeons. The receptors of the lateral line system are
      innervated by 2 pairs of cranial nerves: anterior and posterior lateral line
      nerves. The peripheral processes of the anterior lateral line nerve form
      superficial ophthalmic, buccal, otic and anteroventral rami. The peripheral
      processes of the posterior lateral line nerve form middle, supratemporal and
      lateral rami.

PMID- 22405452
TI  - A short note on the horizontal and vertical movements of a whale shark, Rhincodon
      typus, tracked by satellite telemetry in the South China Sea.
AB  - Whale sharks, a global migratory species, are often reported entangled in fishing
      nets in coastal areas of China. The effectiveness of conservation measures has
      been constrained by very limited knowledge on their movements and preferred
      habitats in the coastal areas of China. For the first time, we tracked the
      movements of 2 whale sharks by satellite telemetry in Mainland China. The
      tracking results of 1 whale shark revealed that it travelled in the South China
      Sea in a south-eastern direction, parallel to the eastern coast of Vietnam. Total
      distance travelled was 1018 km, in approximately 74 days, with a mean speed of 14
      km per day. It appeared to head towards the cool upwelling zones in southern
      Vietnam at the time of the tag's detachment. In our study, it was observed that
      this whale shark was a surface dweller and spent approximately 45% of its time
      above 10 m water depth and 90% of its time above 50 m depth. It also tended to
      stay in water temperatures between 27 and 30  degrees C, and was rarely recorded
      in water below 20  degrees C. This preliminary study indicates the importance of
      shallow waters as the foraging habitat for whale sharks, and has implications for
      their management and conservation.

PMID- 22405453
TI  - Yersinia pestis: examining wildlife plague surveillance in China and the USA.
AB  - Plague is a zoonotic disease caused by the bacterium Yersinia pestis Lehmann and
      Neumann, 1896. Although it is essentially a disease of rodents, plague can also
      be transmitted to people. Historically, plague has caused massive morbidity and
      mortality events in human populations, and has recently been classified as a
      reemerging disease in many parts of the world. This public health threat has led
      many countries to set up wild and domestic animal surveillance programs in an
      attempt to monitor plague activity that could potentially spill over into human
      populations. Both China and the USA have plague surveillance programs in place,
      but the disease dynamics differ in each country. We present data on plague
      seroprevalence in wildlife and review different approaches for plague
      surveillance in the 2 countries. The need to better comprehend plague dynamics,
      combined with the fact that there are still several thousand human plague cases
      per year, make well-designed wildlife surveillance programs a critical part of
      both understanding plague risks to humans and preventing disease outbreaks in the
      future.

PMID- 22405454
TI  - The Hans classificator does not predict outcome in diffuse large B cell lymphoma
      in a large multicenter retrospective analysis of R-CHOP treated patients.

PMID- 22405455
TI  - A migraine as initial presentation of celiac disease.
AB  - Celiac disease (CD), also known as gluten-sensitive enteropathy, is a prevalent
      auto-immune disorder. The silent form of CD seems to be more frequent than
      expected. CD has been associated with neurologic and psychiatric disorders,
      notably cerebellar ataxia, peripheral neuropathy, epilepsy, dementia and
      depression. Migraine is a rare complication of CD. We report a case of CD
      revealed by a migraine. Apparently no case of celiac disease revealed by migraine
      has been reported in the literature.

PMID- 22405456
TI  - [Anti-GAD antibodies in paraneoplastic cerebellar ataxia associated with limbic
      encephalitis and autonomic dysfunction].
AB  - INTRODUCTION: Cerebellar ataxia and stiff person-syndrome are the main
      neurological syndromes associated with antibodies to glutamic acid decarboxylase
      (GAD). CASE REPORT: A 59-year-old patient, with history of polymyalgia rheumatica
      and active smoking, was admitted for subacute cerebellar ataxia and memory
      dysfunction explained by limbic encephalitis on brain MRI. He also presented with
      orthostatic hypotension and erectile dysfunction revealing autonomic dysfunction.
      CSF was inflammatory and antibodies to GAD were positive. Onconeuronal antibodies
      including GABA(B) receptor antibodies were negative. Patient's condition quickly
      improved after intravenous immunoglobulins. A few months later, a small cell lung
      carcinoma was diagnosed and precociously treated. CONCLUSION: This case report
      underlines the importance of appropriate studies to confirm a primitive
      neoplasia, when confronted with limbic encephalitis and cerebellar ataxia, even
      if anti-GAD antibodies rarely define paraneoplastic syndromes.

PMID- 22405457
TI  - [Language and swallowing disorders in acute stroke patients: tools and early
      management].
AB  - INTRODUCTION: The contribution of stroke units to improve morbidity, mortality
      and recovery in stroke victims is clearly demonstrated. However, acute management
      of language disorders in these specialized units is controversial and little
      standardization is seen for the management of swallowing disorders. STATE OF THE
      ART: The recently validated French scale for rapid screening for language
      disorders (LAST) in acute stroke patients should enable optimal detection and
      early management. A standardized protocol should be used to screen for and manage
      swallowing disorders. This protocol should include daily evaluations,
      individually tailored rehabilitation sessions, adaptation of food textures,
      patient education for adequate eating position, team training, and information
      for families. PERSPECTIVES AND CONCLUSIONS: These protocols imply co-operation
      and coordination between the medical and allied profession teams and the daily
      presence of a speech and language therapist. This presence is crucial for
      patients in stroke units to achieve the full benefits of the management scheme
      proposed in this paper.

PMID- 22405458
TI  - Evaluation of visual recognition memory for the early diagnosis of Alzheimer's
      disease in patients over 75 years.
AB  - INTRODUCTION: Current diagnostic criteria of Alzheimer Disease (AD) are mainly
      based on clinical definition. In France, the Delayed Matching Sample (DMS48)
      test, a recently introduced test that explores visual object recognition, is
      recommended for the early diagnosis of AD. However, little is known on the DMS48
      performances of older subjects over 75 years. Therefore, our aim was to assess
      its specific clinical value for early detection of AD in older patients. METHOD:
      We studied 93 consecutive patients over 75 years from an expert memory clinic in
      a geriatric hospital. This population included 31 patients with single domain
      amnestic Mild Cognitive Impairment (aMCI), 31 AD patients and 31 controls
      subjects. RESULTS AND DISCUSSION: The aMCI and AD performances on the DMS48 were
      significantly lower than those of the control subjects (set 1 and set 2, P<10(
      7)). The DMS48 performances in the healthy group appeared closely related to the
      previously published normative data. However, the DMS48 performances appeared
      unexpectedly high in these older patients, especially in the AD subgroup (set 1,
      82.2+/-12.1 and set 2, 75.2+/-16.2). Moreover, there was an unexpected frequent
      discordance between the results on the DMS48 and the Free and Cued Selective
      Reminding tests (FCSR). The DMS test appears useful for highlighting the
      heterogeneity of the syndromes of aMCI and AD in old-old people aged 75+: our
      results also underline the need for further characterization of cognitive
      impairment in this fastest growing subgroup of patients.

PMID- 22405459
TI  - [Miller-Fisher syndrome and influenza A].

PMID- 22405460
TI  - [Epilepsy in Lao Popular Democratic Republic: difficult procurement of a first
      line antiepileptic contributes to widening the treatment gap].
AB  - INTRODUCTION: In Laos, over 95% of people with epilepsy (PWE) do not receive a
      proper treatment. Traditional beliefs and practices have long explained this wide
      treatment gap. From 2008 to 2010 we evaluated the procurement process for
      phenobarbital, the leading first-line antiepileptic drug (AED) in Laos, and its
      availability at a national scale as a potential additional major cause of this
      treatment gap in Laos. METHODS: Data were drawn from several surveys conducted
      from 2008 to 2010: (i) semi structured interviews of key persons from the
      Ministry of Health and from pharmaceutical factories, wholesalers, pharmacists,
      neurologists, psychiatrists, and non-governmental organisations; (ii)
      retrospective survey of AED prescriptions in three main hospitals of Vientiane
      the capital city during two randomised weeks from June to August 2009; (iii) self
      administered questionnaires of pediatricians regarding their knowledge about
      phenobarbital; (iv) a national survey of the AED availability in pharmacies and
      drug shops in 16/17 provinces, 16 districts and 96 villages (multistage
      randomised survey) in 2010 and a survey among the population in 2009. RESULTS:
      Phenobarbital is imported in Laos via a carefully controlled importation process
      either as raw material to be processed by factory N(o) 2 or in the form of
      tablets. The International Narcotics Control Board (Vienne) delivers a yearly
      quota of 25kg of raw phenobarbital to the Food and Drug department (FDA). This
      allows the production of 245000 tablets per year (around 671 annual adult
      treatments). The overall importation process for phenobarbital lasts 6months.
      Grade 1 pharmacists (mostly located in urban areas) and regional and district
      hospitals are authorized to deliver phenobarbital. The cost of phenobarbital
      ranged from 0.11 to 0.2US dollars/tablet per day (39 to 67US dollars per year).
      High cost of transportation and increased cost of phenobarbital (5- to 10-fold
      greater than the international market) contribute to reduce access to treatment.
      CONCLUSION: Needs for phenobarbital at delivery sites should be re-assessed by
      the health authorities based on the expected number of PWE. Improved training of
      health and pharmacist personnel and increased awareness of the population
      concerning effective long-term treatment for epilepsy are crucial to improve
      access of PWE to AED in Laos.

PMID- 22405461
TI  - Tropical spastic paraparesis and HTLV-1 associated myelopathy: clinical,
      epidemiological, virological and therapeutic aspects.
AB  - In 1980, Human T cell leukemia/lymphoma virus type 1 (HTLV-1) was the first
      oncogenic human retrovirus to be discovered. HTLV-1 belongs to the Retroviridae
      family, the Orthoretrovirinae subfamily and to the deltaretrovirus genus. HTLV-1
      preferentially infects CD4(+) lymphoid cells in vivo. Three molecules have been
      identified for binding and/or entry of HTLV-1: heparan sulfate proteoglycans,
      neuropilin-1, and glucose transporter 1. An efficient transfer of the virus from
      an infected cell to a target cell can occur through the formation of a viral
      synapse and/or by virofilm structure. As for all retroviruses, HTLV-1 genome
      possesses three major ORFs (gag, pol and env) encoding the structural and
      enzymatic proteins. HTLV-1 encodes also some regulatory and auxillary proteins
      including the tax protein with transforming activities and the HBZ protein which
      plays a role in the proliferation and maintenance of the leukemic cells. HTLV-1
      is present throughout the world with clusters of high endemicity including mainly
      Southern Japan, the Caribbean region, areas in South America and in intertropical
      Africa. The worldwide HTLV-1 infected population is estimated to be around 10-20
      million. HTLV-1 has three modes of transmission: (1): mother to child, mainly
      linked to prolonged breast-feeding; (2): sexual, mainly occurring from male to
      female and (3): contaminated blood products. HTLV-1 possesses a remarkable
      genetic stability. HTLV-1 is the etiological agent of mainly two severe diseases:
      a malignant T CD4(+) cell lymphoproliferation, of very poor prognosis, named
      Adult T cell Leukemia/Lymphoma (ATLL), and a chronic neuro-myelopathy named
      Tropical spastic paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM). The lifetime
      risk among HTLV-1 carriers is estimated to be around 0.25 to 3%. TSP/HAM mainly
      occurs in adults, with a mean age at onset of 40-50 years and it is more common
      in women than in men. Blood transfusion is a major risk factor for TSP/HAM
      development. Clinically, TSP/HAM is mainly defined as a chronic spastic
      paraparesis and minor sensory signs. The onset is insidious with often gait
      disturbance and urinary symptoms. In more than 90% of the cases, the neurological
      features involve: spasticity and/or hyperreflexia of the lower extremities,
      urinary bladder disturbance, lower extremity muscle weakness, and in around 50%
      of the cases, sensory disturbances with low back pain. Central functions and
      cranial nerves are usually spared. The clinical course is generally progressive
      without remission. High levels of antibodies titers directed against HTLV-1
      antigens are present in blood and cerebrospinal fluid (CSF). A high HTLV-1
      proviral load is frequently observed in the blood. Mild to moderate increase of
      proteins may be present in the CSF. However, intrathecal production of specific
      HTLV-1 antibody index provides additional data to support the diagnosis. Brain
      white matter lesions on magnetic resonance imaging are frequent. A mild atrophy
      of the thoracic spinal cord can also be observed. Pathologically, it is
      characterized by a chronic inflammation with perivascular lymphocytic cuffing and
      mild parenchymal lymphocytic infiltrates. The cells are mostly CD4(+) in early
      disease and mostly CD8(+) in latter disease. Pyramidal tract damage with myelin
      and axonal loss, mainly in the lower thoracic spinal cord are observed. TSP/HAM
      pathogenesis is still poorly understood and viral and host factors as the
      proviral load and the cellular immune response play a major role in disease
      progression. TSP/HAM can be associated with other HTLV-1 associated symptoms
      (uveitis, myositis, infective dermatitis). Therapy of TSP/HAM remains
      disappointing and symptomatic treatment remains still the mainstay of therapy.

PMID- 22405462
TI  - [Leptomeningeal melanocytosis: a fatal course of a benign tumor].

PMID- 22405463
TI  - Co-infection of HIV and tropical infectious agents that affect the nervous
      system.
AB  - Tropical infections refer to a group of diseases usually located in regions with
      a warm climate, particularly affecting developing countries, partly because of
      the conditions that allow them to thrive. However, due to the increased
      international travel, infectious agents that were previously limited to tropical
      regions pose an increasing threat to populations at risk for opportunistic
      infection (OI), especially those infected with the HIV. Tropical infections can
      facilitate HIV transmission and accelerate the progression of asymptomatic HIV
      infection to AIDS. Some have the potential to alter the epidemiology, natural
      history, and/or response to treatment of the other. The introduction of highly
      active antiretroviral therapy has provided a huge benefit for the vast majority
      of patients infected with the HIV, by allowing the immune system to recover,
      improving the clinical and radiological results and reducing the number of OI. On
      the other hand, some patients have developed various disorders of immune
      reconstitution, resulting in either hyper-immune inflammatory response to an
      exogenous antigen or autoimmunity. A significant proportion of these cases have
      been reported in immigrants from tropical countries to high-income countries,
      therefore awareness of these phenomena is needed since clinical presentations are
      often atypical and pose diagnostic challenges. This article reviews some of the
      key diagnostic aspects of tropical infections associated with HIV infection.

PMID- 22405465
TI  - Isolation of Campylobacter from feral swine (Sus scrofa) on the ranch associated
      with the 2006 Escherichia coli O157:H7 spinach outbreak investigation in
      California.
AB  - We report the isolation of Campylobacter species from the same population of
      feral swine that was investigated in San Benito County, California, during the
      2006 spinach-related Escherichia coli O157:H7 outbreak. This is the first survey
      of Campylobacter in a free-ranging feral swine population in the United States.
      Campylobacter species were cultured from buccal and rectal-anal swabs, colonic
      faeces and tonsils using a combination of selective enrichment and antibiotic
      free membrane filtration methods. Matrix-assisted laser desorption ionization
      time of flight mass spectrometry (MALDI-TOF-MS, Bruker Daltonics, Inc.,
      Billerica, MA, USA) was used to identify species followed by confirmatory
      multiplex PCR or 16S rRNA sequencing. Genetic relatedness of Campylobacter jejuni
      and Campylobacter coli strains was determined by multilocus sequence typing
      (MLST) and porA allele sequencing. Altogether, 12 (40%) of 30 feral swine
      gastrointestinal and oral cavity specimens were positive, and six species were
      isolated: Campylobacter coli, Campylobacter fetus, Campylobacter
      hyointestinalsis, Campylobacter jejuni, Campylobacter lanienae and Campylobacter
      sputorum. Campylobacter jejuni subtypes were closely related to MLST sequence
      type 21 (ST-21) and had identical porA sequences. Campylobacter coli subtypes
      were unrelated to isolates in the pubMLST/porA database. This feral swine
      population lived in close association with a 'grassfed' beef cattle herd adjacent
      to spinach and other leafy green row crop fields. The findings underscore the
      importance of protecting raw vegetable crops from faecal contamination by wild or
      feral animals. The study also illustrates a potential risk of Campylobacter
      exposure for hunters during handling and processing of wild swine meat.

PMID- 22405464
TI  - Ovarian serous carcinoma: recent concepts on its origin and carcinogenesis.
AB  - Recent morphologic and molecular genetic studies have led to a paradigm shift in
      our conceptualization of the carcinogenesis and histogenesis of pelvic (non
      uterine) serous carcinomas. It appears that both low-grade and high-grade pelvic
      serous carcinomas that have traditionally been classified as ovarian in origin,
      actually originate, at least in a significant subset, from the distal fallopian
      tube. Clonal expansions of the tubal secretory cell probably give rise to serous
      carcinomas, and the degree of ciliated conversion is a function of the degree to
      which the genetic hits deregulate normal differentiation. In this article, the
      authors review the evidentiary basis for aforementioned paradigm shift, as well
      as its potential clinical implications.

PMID- 22405466
TI  - Bone mineral density and associated parameters in pre-pubertal children with
      asthma treated with long-term fluticasone propionate.
AB  - AIMS: The primary aim of the objective of the study was to determine the effects
      of long-term treatment with the recommended dose of inhaled fluticasone
      propionate spray usage on bone mineral status in children with asthma. METHODS:
      This cross-sectional, case-control study was of 270 pre-pubertal children with
      asthma, who had used inhaled fluticasone propionate at a mean daily dose of 200
      MUg (range: 200-350 MUg) for at least 5 years. The bone mineral density (BMD) of
      the lumbar spine was measured by dual-energy X-ray absorptiometry (DEXA). The
      results were compared to untreated controls (n=200), who were newly diagnosed
      children with asthma without any corticosteroid treatment. RESULTS: The 270 study
      patients (175 males) were aged between 6 and 13 years. The average age (+/-SEM)
      was 9.2+/-0.6 years, and the mean (+/-SEM) steroid dosage used was 183.3+/-57.0
      MUg daily, with 236.5+/-17.2 g total steroid use during treatment. Between the
      study and the control groups, no significant difference was observed in BMD
      (p>0.05). CONCLUSION: The findings suggest that long-term periodical treatment
      for 5 years with inhaled fluticasone propionate, 100 MUg twice daily, in children
      with asthma revealed no negative effect on bone mineral density by using DEXA.

PMID- 22405467
TI  - Characteristics of patients with allergic rhinitis in an outpatient clinic: a
      retrospective study.
AB  - BACKGROUND: Allergic rhinitis affects a significant proportion of the European
      population. Few surveys have investigated this disorder in Greek adults. Our
      objective was to describe the characteristics of patients with allergic rhinitis
      in an adult outpatient clinic in Thessaloniki, Greece. METHODS: We studied the
      medical records of adult patients referred to a Clinical Immunology outpatient
      clinic from 2001 to 2007. The diagnostic procedure was not changed during the
      whole study period, including the same questionnaire used at the time of
      diagnosis, skin prick tests, and serum specific IgE. RESULTS: A total of 1851
      patient files with diagnosed allergies were analysed and allergic rhinitis was
      confirmed in 711 subjects (38.4%). According to ARIA classification, persistent
      allergic rhinitis was more prevalent than intermittent (54.9% vs. 45.1%), while
      60.8% of subjects suffered from moderate/severe disease. In multivariable
      analysis, factors associated with allergic rhinitis were age (for every 10 years
      increase, OR: 0.84, 95% CI: 0.77-0.91; p<0.001); working in school environment
      (teachers or students) (OR: 1.46, 95% CI: 1.05-2.02; p=0.023); parental history
      of respiratory allergy (OR: 2.41, 95% CI: 1.69-3.43; p<0.001); smoking (OR: 0.71,
      95% CI: 0.55-0.91; p=0.007); presence of allergic conjunctivitis (OR: 6.16, 95%
      CI: 4.71-8.06; p<0.001); and asthma (OR: 2.17, 95% CI: 1.57-3.01; p<0.001).
      Analysis after multiple imputation corroborated the complete case analysis
      results. CONCLUSIONS: Allergic rhinitis was documented in 38.4% of studied
      patients and was frequently characterised by significant morbidity. Factors
      associated with allergic rhinitis provide insight into the epidemiology of this
      disorder in our region. Further studies on the general population would
      contribute to evaluating allergic rhinitis more comprehensively.

PMID- 22405469
TI  - Pathologic complete response to neoadjuvant therapy in patients with pancreatic
      ductal adenocarcinoma means no residual tumor: no need to assess "viability".

PMID- 22405468
TI  - Weight status and gender-related differences in motor skills and in child care -
      based physical activity in young children.
AB  - BACKGROUND: Over the last decades, a decline in motor skills and in physical
      activity and an increase in obesity has been observed in children. However, there
      is a lack of data in young children. We tested if differences in motor skills and
      in physical activity according to weight or gender were already present in 2- to
      4-year-old children. METHODS: Fifty-eight child care centers in the French part
      of Switzerland were randomly selected for the Youp'la bouge study. Motor skills
      were assessed by an obstacle course including 5 motor skills, derived from the
      Zurich Neuromotor Assessment test. Physical activity was measured with
      accelerometers (GT1M, Actigraph, Florida, USA) using age-adapted cut-offs. Weight
      status was assessed using the International Obesity Task Force criteria (healthy
      weight vs overweight) for body mass index (BMI). RESULTS: Of the 529 children
      (49% girls, 3.4 +/- 0.6 years, BMI 16.2 +/- 1.2 kg/m2), 13% were overweight.
      There were no significant weight status-related differences in the single skills
      of the obstacle course, but there was a trend (p = 0.059) for a lower performance
      of overweight children in the overall motor skills score. No significant weight
      status-related differences in child care-based physical activity were observed.
      No gender-related differences were found in the overall motor skills score, but
      boys performed better than girls in 2 of the 5 motor skills (p <= 0.04). Total
      physical activity as well as time spent in moderate-vigorous and in vigorous
      activity during child care were 12-25% higher and sedentary activity 5% lower in
      boys compared to girls (all p < 0.01). CONCLUSIONS: At this early age, there were
      no significant weight status- or gender-related differences in global motor
      skills. However, in accordance to data in older children, child care-based
      physical activity was higher in boys compared to girls. These results are
      important to consider when establishing physical activity recommendations or
      targeting health promotion interventions in young children.

PMID- 22405470
TI  - pH-sensitive chitosan-derived nanoparticles as doxorubicin carriers for effective
      anti-tumor activity: preparation and in vitro evaluation.
AB  - pH-sensitive self-aggregated nanoparticles (SNPs), based on amphiphilic
      deoxycholic acid (DOCA) modified carboxymethyl chitosan (DCMC), were prepared for
      delivery of the anticancer drug doxorubicin (DOX). DCMCs with different degrees
      of substitution (DS) of DOCA were initially synthesized and characterized. Based
      on self-aggregation, DCMC formed nanoparticles with size ranging from 87 to 174
      nm. The critical aggregation concentration (CAC) decreased on increasing the DS
      of DOCA. Moreover, the DCMC SNPs showed an acidic pH-induced aggregation and
      deformation behavior. The DOX-loaded SNPs ([D]NP) exhibited a sustained drug
      release manner, which could be accelerated by an acidic pH, but delayed by a
      higher DS of DOCA. Antitumor efficacy results showed that [D]NP could suppress
      both sensitive and resistant MCF-7 cells effectively in a dose- and time
      dependent manner. The enhanced cellular uptake and greater retention of [D]NP in
      drug-resistant cells, as evidenced by confocal microscopy and flow cytometry,
      contributed to a superior efficacy of [D]NP over free DOX. These results suggest
      the potential of DCMC SNPs as carriers for the hydrophobic drug DOX for effective
      cancer therapy against drug-resistant tumors.

PMID- 22405471
TI  - Adsorption of bovine serum albumin on nano and bulk oxide particles in deionized
      water.
AB  - In this work, the influence of particle size and surface functional groups on the
      adsorption behavior of bovine serum albumin (BSA) by three types of oxide
      nanoparticles (NPs), TiO(2) (50+/-5 nm), SiO(2) (30+/-5 nm), and Al(2)O(3) (150+/
      5 nm for alpha type and 60+/-5 nm for gamma type) was investigated in deionized
      water, in order to explore their interaction mechanisms without competitive
      influence of other ions. Bulkparticles (BPs) were also used for comparison with
      NPs. BSA adsorption maxima on oxide particles were controlled by the surface area
      and hydrogen content, while adsorption process was primarily induced by
      electrostatic interaction, hydrophobic interaction and ligand exchange between
      BSA and oxide surfaces. With the increase of hydrogen content, the BSA adsorption
      mechanism switched from mainly hydrophobic interaction to hydrogen bonding and
      ligand exchange. Calculations, based on surface area and BSA size, suggested that
      a multilayer of BSA covered on alpha-Al(2)O(3), and single layer on the other
      oxide particle surfaces. BPs led to greater conformational change of BSA
      molecules after the adsorption on the surfaces of oxide particles though NPs
      adsorbed more BSA than BPs.

PMID- 22405472
TI  - Different doses of supplemental vitamin D maintain interleukin-5 without altering
      skeletal muscle strength: a randomized, double-blind, placebo-controlled study in
      vitamin D sufficient adults.
AB  - BACKGROUND: Supplemental vitamin D modulates inflammatory cytokines and skeletal
      muscle function, but results are inconsistent. It is unknown if these
      inconsistencies are dependent on the supplemental dose of vitamin D. Therefore,
      the purpose of this study was to identify the influence of different doses of
      supplemental vitamin D on inflammatory cytokines and muscular strength in young
      adults. METHODS: Men (n = 15) and women (n = 15) received a daily placebo or
      vitamin D supplement (200 or 4000 IU) for 28-d during the winter. Serum 25
      hydroxyvitamin D (25(OH)D), cytokine concentrations and muscular (leg) strength
      measurements were performed prior to and during supplementation. Statistical
      significance of data were assessed with a two-way (time, treatment) analysis of
      variance (ANOVA) with repeated measures, followed by a Tukey's Honestly
      Significant Difference to test multiple pairwise comparisons. RESULTS: Upon
      enrollment, 63% of the subjects were vitamin D sufficient (serum 25(OH)D >= 30
      ng/ml). Serum 25(OH)D and interleukin (IL)-5 decreased (P < 0.05) across time in
      the placebo group. Supplemental vitamin D at 200 IU maintained serum 25(OH)D
      concentrations and increased IL-5 (P < 0.05). Supplemental vitamin D at 4000 IU
      increased (P < 0.05) serum 25(OH)D without altering IL-5 concentrations. Although
      serum 25(OH)D concentrations correlated (P < 0.05) with muscle strength, muscle
      strength was not changed by supplemental vitamin D. CONCLUSION: In young adults
      who were vitamin D sufficient prior to supplementation, we conclude that a low
      daily dose of supplemental vitamin D prevents serum 25(OH)D and IL-5
      concentration decreases, and that muscular strength does not parallel the 25(OH)D
      increase induced by a high-daily dose of supplemental vitamin D. Considering that
      IL-5 protects against viruses and bacterial infections, these findings could have
      a broad physiological importance regarding the ability of vitamin D sufficiency
      to mediate the immune systems protection against infection.

PMID- 22405473
TI  - Comparison of alfaxalone and propofol administered as total intravenous
      anaesthesia for ovariohysterectomy in dogs.
AB  - OBJECTIVE: To compare the anaesthetic and cardiopulmonary effects of alfaxalone
      with propofol when used for total intravenous anaesthesia (TIVA) during
      ovariohysterectomy in dogs. STUDY DESIGN: A prospective non-blinded randomized
      clinical study. ANIMALS: Fourteen healthy female crossbred bitches, aged 0.5-5
      years and weight 16-42 kg. METHODS: Dogs were premedicated with acepromazine 0.01
      mg kg(-1) and morphine 0.4 mg kg(-1). Anaesthesia was induced and maintained with
      either propofol or alfaxalone to effect for tracheal intubation followed by an
      infusion of the same agent. Dogs breathed spontaneously via a 'circle' circuit,
      with oxygen supplementation. Cardiopulmonary parameters (respiratory and heart
      rates, end-tidal carbon dioxide, tidal volume, and invasive blood pressures) were
      measured continuously and recorded at intervals related to the surgical
      procedure. Arterial blood samples were analysed for blood gas values. Quality of
      induction and recovery, and recovery times were determined. Non-parametric data
      were tested for significant differences between groups using the Mann-Whitney U
      test and repeatedly measured data (normally distributed) for significant
      differences between and within groups by anova. RESULTS: Both propofol and
      alphaxalone injection and subsequent infusions resulted in smooth, rapid
      induction and satisfactory maintenance of anaesthesia. Doses for induction (mean
      +/- SD) were 5.8 +/- 0.30 and 1.9 +/- 0.07 mg kg(-1) and for the CRIs, 0.37 +/-
      0.09 and 0.11 +/- 0.01 mg kg(-1) per minute for propofol and alfaxalone
      respectively. Median (IQR) recovery times were to sternal 45 (33-69) and 60 (46
      61) and to standing 74 (69-76) and 90 (85-107) for propofol and alphaxalone
      respectively. Recovery quality was good. Cardiopulmonary effects did not differ
      between groups. Hypoventilation occurred in both groups. CONCLUSIONS AND CLINICAL
      RELEVANCE: Following premedication with acepromazine and morphine, both propofol
      and alphaxalone produce good quality anaesthesia adequate for ovariohysterectomy.
      Hypoventilation occurs suggesting a need for ventilatory support during prolonged
      infusion periods with either anaesthetic agent.

PMID- 22405474
TI  - Healthy Aging 2.0: the potential of new media and technology.

PMID- 22405475
TI  - Influence of change in aerobic fitness and weight on prevalence of metabolic
      syndrome.
AB  - INTRODUCTION: The metabolic syndrome is the clustering of several cardiometabolic
      risk factors that can lead to the development of coronary heart disease and type
      2 diabetes. We evaluated whether a change in aerobic fitness resulting from a
      lifestyle intervention could significantly change the odds of metabolic syndrome
      prevalence. METHODS: Participants (n = 810) were recruited into PREMIER, a
      multicenter, randomized, controlled clinical trial with outcome assessments at 6
      and 18 months. The primary eligibility criterion was a diagnosis of
      prehypertension or stage 1 hypertension. PREMIER randomized participants to 2
      lifestyle interventions, both of which included increased physical activity, or
      an advice-only control group. Participants completed a submaximal treadmill
      exercise test; we used reduction in heart rate as the measure of improved aerobic
      fitness. We used logistic regression to determine intervention effects on
      metabolic syndrome prevalence. Our models controlled for dietary pattern change.
      RESULTS: The lifestyle interventions had no significant effect on metabolic
      syndrome prevalence at 6 months or 18 months. When combining intervention and
      control groups, at 6 and 18 months, a 1-beat-per-minute reduction in heart rate
      was associated with a 4% reduction in prevalence of metabolic syndrome (P <
      .001). When we tested for weight change as a mediator, the association was no
      longer significant. CONCLUSION: Increased aerobic fitness may reduce prevalence
      of metabolic syndrome. This association appears to be mediated through
      concomitant weight change.

PMID- 22405476
TI  - The mental health needs of out-of-school adolescents and young adults: an
      intervention conducted in employment training programs, Baltimore, Maryland, 2007
      2008.
AB  - INTRODUCTION: Despite the large number of adolescents and young adults in
      employment training programs, a population that has poorer health and greater
      health risk than similarly aged in-school peers, we are unaware of any health
      interventions that have been evaluated in this setting. The primary objective of
      our study was to evaluate changes in depressive symptoms, coping strategies, and
      receipt of mental health services among low-income African American adolescents
      and young adults receiving a mental health intervention integrated into an
      employment training program. METHODS: The intervention consisted of an on-site
      mental health clinician, a peer-led depression prevention intervention, and
      training sessions for employment training staff. A pretest-posttest design
      assessed depressive symptoms, coping strategies, and receipt of mental health
      services at baseline and 12-month follow-up. Complete baseline and follow-up data
      were available for 136 of 218 eligible participants. Most study participants were
      African American (98%); average age was 18.8 years. RESULTS: The intervention had
      no effect on depressive symptoms or coping strategies. The percentage of
      participants who used mental health services at follow-up increased, but not
      significantly. Age was associated with use of active and support-seeking coping
      strategies, whereas use of mental health services before program enrollment was
      associated with use of mental health services at follow-up. CONCLUSION:
      Alternative intervention strategies may be needed to decrease the severity of
      depressive symptoms and increase use of coping strategies among adolescents and
      young adults in employment training programs. Future research evaluating such
      interventions should use quasi-experimental or experimental designs to provide
      evidence of intervention effect.

PMID- 22405477
TI  - Behavioral actions of alcohol: phenotypic relations from multivariate analysis of
      mutant mouse data.
AB  - Behavioral studies on genetically diverse mice have proven powerful for
      determining relationships between phenotypes and have been widely used in alcohol
      research. Most of these studies rely on naturally occurring genetic polymorphisms
      among inbred strains and selected lines. Another approach is to introduce
      variation by engineering single-gene mutations in mice. We have tested 37
      different mutant mice and their wild-type controls for a variety (31) of
      behaviors and have mined this data set by K-means clustering and analysis of
      correlations. We found a correlation between a stress-related response (activity
      in a novel environment) and alcohol consumption and preference for saccharin. We
      confirmed several relationships detected in earlier genetic studies, including
      positive correlation of alcohol consumption with saccharin consumption and
      negative correlations with conditioned taste aversion and alcohol withdrawal
      severity. Introduction of single-gene mutations either eliminated or greatly
      diminished these correlations. The three tests of alcohol consumption used
      (continuous two-bottle choice and two limited access tests: drinking in the dark
      and sustained high alcohol consumption) share a relationship with saccharin
      consumption, but differ from each other in their correlation networks. We suggest
      that alcohol consumption is controlled by multiple physiological systems where
      single-gene mutations can disrupt the networks of such systems.

PMID- 22405478
TI  - Incidence of hospitalization due to child maltreatment in Taiwan, 1996-2007: a
      nationwide population-based study.
AB  - OBJECTIVES: Little is known regarding the epidemiology of child maltreatment in
      Asian countries. This study aimed to examine the incidence of hospitalization
      coded as due to child maltreatment in Taiwan. METHODS: We used inpatient claims
      data of the National Health Insurance for the years 1996 through 2007 for
      estimation. Hospitalization of children aged 0-12 years with an ICD-9-CM code
      995.5 "maltreatment syndrome" or E960-E969 "assault" in the main or secondary
      discharge diagnosis in claims data was defined as hospitalization due to child
      maltreatment. Poisson regression was used to examine the trends. RESULTS: A total
      of 1,726 children with 1,780 hospitalizations due to child maltreatment were
      identified during 1996-2007. The averaged annual incidence over 1996-2007 was
      13.2/100,000 for infants, 3.5/100,000 for children aged 1-3 years, 2.1/100,000
      for children aged 4-6 years and 3.3/100,000 for children aged 7-12 years. The
      incidence increased most among the infant group, from 4.8/100,000 in 1996-1997 to
      25.4/100,000 in 2006-2007, a greater than 5-fold increase. The magnitude of the
      increase in incidence decreased with age, and no change in incidence was noted
      among children aged 7-12 years. The drastic increase in incidence in infants
      since 2003 corresponds with the introduction of use of ICD-9-CM code 995.55
      "shaken infant syndrome" in Taiwan since 2003. Head injury was the main type of
      injury in all age groups. CONCLUSIONS: The incidence of hospitalization coded as
      due to child maltreatment in Taiwan differed by age group. Infants had the
      highest and the largest increase in incidence during the past decade. The
      increase might be due to improvement in awareness, competence and willingness to
      diagnose child maltreatment of medical staff in hospitals during the past decade
      after the revision of Child Welfare Law in 1993 and the new ICD-9-CM code for
      "shaken infant syndrome" being used since 2003. PRACTICE IMPLICATIONS: Physicians
      and nursing staff should be aware of and provide the detailed and specific
      information needed for proper discharge diagnosis coding, from which valid
      estimation of the incidence of hospitalization due to child maltreatment can be
      made. Administrative data should include both the N-code and E-code for each case
      of child maltreatment hospitalization to provide more complete information.

PMID- 22405479
TI  - Development of standardized clinical training cases for diagnosis of sexual abuse
      using a secure telehealth application.
AB  - OBJECTIVES: The training of physicians, nurse examiners, social workers and other
      health professional on the evidentiary findings of sexual abuse in children is
      challenging. Our objective was to develop peer reviewed training cases for
      medical examiners of child sexual abuse, using a secure web based telehealth
      application (TeleCAM). METHODS: Sixty de-identified cases developed by 2 child
      abuse pediatricians, were stratified by availability of information (minimal,
      moderate, comprehensive) for both positive and negative child sexual abuse
      findings. These cases were narrowed to a set of 30 cases through an expert peer
      review process using pediatricians with extensive expertise in the evaluation of
      child sexual abuse. A previously studied secure web-based telehealth application
      TeleCAM which contains a child abuse workflow, was used to develop, disseminate
      and review cases. A series of Free Margin agreement statistics are used to select
      those cases with the highest rates of agreement. A final set of 30 cases are
      stratified equally by availability of information and for both positive and
      negative findings. Mantel Haenszel Chi-square was used for trend analysis of the
      ordered categorical variables. RESULTS: The highest degrees of inter-rater
      reliability was found in cases with moderate to comprehensive information. Cases
      with minimal data had poor kappa agreement indicating that availability of
      differing levels and types of information contribute to variability in diagnostic
      findings. CONCLUSION: These final cases will be further studied with medical
      examiners in various settings utilizing TeleCAM as the application for
      dissemination.

PMID- 22405480
TI  - The influence of prior expectations on facial expression discrimination in
      schizophrenia.
AB  - BACKGROUND: Belief inflexibility is a thinking style observed in patients with
      schizophrenia, in which patients tend to refute evidence that runs counter to
      their prior beliefs. This bias has been related to a dominance of prior
      expectations (prior beliefs) over incoming sensory evidence. In this study we
      investigated the reliance on prior expectations for the processing of emotional
      faces in schizophrenia. METHOD: Eighteen patients with schizophrenia and 18
      healthy controls were presented with sequences of emotional (happy, fearful,
      angry or neutral) faces. Perceptual decisions were biased towards a particular
      expression by a specific instruction at the start of each sequence, referred to
      as the context in which stimuli occurred. Participants were required to judge the
      emotion on each face and the effect of the context on emotion discrimination was
      investigated. RESULTS: For threatening emotions (anger and fear), there was a
      performance cost for facial expressions that were incongruent with, and
      perceptually close to, the expression named in the instruction. For example, for
      angry faces, participants in both groups made more errors and reaction times
      (RTs) were longer when they were asked to look out for fearful faces compared
      with the other contexts. This bias against sensory evidence that runs counter to
      prior information was stronger in the patients, evidenced by a group by context
      interaction in accuracy and RTs for anger and fear respectively. CONCLUSIONS:
      Overall, the present data suggest an overdependence on prior expectations for
      threatening stimuli, reflecting belief inflexibility, in schizophrenia.

PMID- 22405481
TI  - Detection and disposition of JWH-018 and JWH-073 in mice after exposure to "Magic
      Gold" smoke.
AB  - The disposition in mice of the cannabimimetics JWH-018 and JWH-073 in blood and
      brain following inhalation of the smoke from the herbal incense product (HIP)
      "Magic Gold" containing 3.6% JWH-018, 5.7% JWH-073 and less than 0.1% JWH-398
      (w/w) is presented. Specimens were analyzed by HPLC/MS/MS. The validation of the
      method is also presented. Five C57BL6 mice were sacrificed 20 min after exposure
      to the smoke of 200 mg of "Magic Gold" and a second set of five exposed mice were
      sacrificed after 20 h. Twenty minutes after exposure to "Magic Gold" smoke, blood
      concentrations of JWH-018 ranged from 42 to 160 ng/mL (mean: 88 ng/mL +/- 42) and
      those of JWH-073 ranged from 67 to 244 ng/mL (mean: 134 ng/mL +/- 62). Brain
      concentrations 20 min after exposure to "Magic Gold" smoke for JWH-018 ranged
      from 225 to 453 ng/g (mean: 317 ng/g +/- 81) and those of JWH-073 ranged from 412
      to 873 ng/g (mean: 584 ng/g +/- 163). Twenty hours after exposure to "Magic Gold"
      smoke, JWH-018 was detected and quantified in only two of the five blood samples.
      Blood concentrations of JWH-018 were 3.4 ng/mL and 9.4 ng/mL. JWH-073 was
      detected in only one blood specimen 20 h after exposure at 4.3 ng/mL. Brain
      concentrations 20 h post exposure for JWH-018 ranged from 7 to 32 ng/g (mean: 19
      ng/g +/- 9). JWH-073 was not detected in 20 h post exposure brain specimens. JWH
      398 was not detected in any of the blood or brain samples. The disposition data
      presented with the limited data available from human experience provide
      reasonable expectations for forensic toxicologists in JWH-018 or JWH-073 cases.
      As with THC after smoking marijuana, blood and brain concentrations of JWH-018
      and JWH-073 after HIP smoking can be expected to rise initially to readily
      detected values, and then drop dramatically over the next few hours to several
      ng/mL or ng/g, and finally to be at extremely low or undetectable concentrations
      by 24h apparently due to extensive biotransformation, and redistribution to body
      fat.

PMID- 22405482
TI  - Body recovery from hostile environments--a test of three kits.
AB  - Disaster Victim Identification (DVI) procedures and protocols have largely been
      standardised through the creation of, and amendments to, the INTERPOL DVI Guide.
      Whilst robust in addressing the recovery of mass fatality victims resulting from
      natural disasters, accidents and acts of terrorism, the guide does not explore
      the problematic issue of recovery of fatalities during active conflicts or
      peacekeeping operations where the environment may be hostile and the time taken
      to perform the task may impact significantly on the risk of injury or additional
      fatalities. This study tested the viability of the current UK style body recovery
      kit for use in a hostile environment simulation and compared its performance to
      two new bespoke kits specifically designed by the first author for this purpose.
      The aim was to recover the maximum amount of available physical evidence to
      support possible future judicial review, maintain respectful dignity for the
      deceased and focus on the safety of those fulfilling this task who may be
      operating on the front line. The kits were tested by military personnel
      experienced in hostile environment deployment. The trials showed that the time
      taken to record and recover the deceased could be reduced from 40 min using the
      standard DVI kit to just over 2 min using a bespoke kit. It was also shown that
      evidential recovery was not adversely affected and it is suggested that personal
      safety could be significantly enhanced if the proposed methodology and kit were
      adopted.

PMID- 22405483
TI  - Skin penetration surrogate for the evaluation of less lethal kinetic energy
      munitions.
AB  - Although the benefits of the use of less lethal kinetic energy munitions are
      numerous, there is a need to evaluate the munitions prior to deployment to ensure
      their intended effect. The objective of the current research was to validate a
      surrogate that could be used to predict the risk of penetration of these devices.
      Existing data from biomechanical testing with post-mortem human specimens (PMHS)
      served as the foundation for this research. Development of the surrogate involved
      simulating the various layers of the skin and underlying soft tissues using a
      combination of materials. A standardized 12-gauge impactor was used to assess
      each combination. The energy density that resulted in a 50% risk of penetration
      for the anterior thorax region (23.99 J/cm(2)) from the previous research was
      matched using a specific combination of layers. Twelve various combinations of
      materials were tested with the 50% risk of penetration determined. The final
      validated surrogate consisted of a Laceration Assessment Layer (LAL) of natural
      chamois and .6 cm of closed-cell foam over a Penetration Assessment Layer (PAL)
      of 20% ordnance gelatin. This surrogate predicted a 50% risk of penetration at
      23.88 J/cm(2). Injury risk curves for the PMHS and surrogate development work are
      presented.

PMID- 22405484
TI  - Adenovirus-induced interstitial nephritis following umbilical cord blood
      transplant for chronic lymphocytic leukemia.
AB  - We present a case of a 27-year-old man who received an unrelated donor umbilical
      cord blood transplant for chronic lymphocytic leukemia. His postsurgery course
      was complicated by acute kidney injury, hemorrhagic cystitis, and pancytopenia.
      Transjugular kidney biopsy showed interstitial nephritis. Viral inclusions were
      present in tubular epithelial cells, and in situ hybridization studies confirmed
      the presence of adenovirus. Kidney function improved after a short course of
      cidofovir. Adenovirus-induced interstitial nephritis should be considered in the
      differential diagnosis in all cases of interstitial nephritis occurring in
      immunocompromised patients.

PMID- 22405485
TI  - International comparison of assessments of pharmaceutical innovation.
AB  - INTRODUCTION: This study was undertaken to compare decisions about medicines
      innovation made by two Canadian organizations, the Therapeutic Products
      Directorate (TPD) and the Human Drug Advisory Panel (HDAP), with those made by
      similar organizations in other countries. METHODS: Assessments by TPD and HDAP
      were compared to those made by the Food and Drug Administration (FDA) and the
      drug bulletin Prescrire International, respectively. RESULTS: Between 2004 and
      2009 the TPD gave priority reviews to 46 of 137 (34%) products compared to 71 of
      145 drugs (49%) by the FDA (p=0.011). Of 109 drugs in common the two agreed on
      the review status in 88 (weighted Kappa=0.606). In the same time period HDAP
      categorized 12 of 120 (10%) drugs as innovative while Prescrire did the same for
      49 of 624 (8%) new drugs and new indications for older drugs (p=0.4664). Of 84
      drugs in common the two agreed on the evaluation for 70 (weighted Kappa=0.319).
      DISCUSSION: Differences between the different organizations may be due to a
      variety of factors. These differences have significant policy implications.

PMID- 22405486
TI  - Innovative work behavior in healthcare: the benefit of operational guidelines in
      the treatment of rare diseases.
AB  - OBJECTIVES: Innovative work behavior is a core demand of healthcare professionals
      who treat patients with rare diseases. In healthcare services, determinants of
      innovative work behavior are not completely detected. This paper focuses on how
      the existence of guidelines and the flexibility of healthcare professionals in
      taking on extra roles in the workplace enable innovative work behavior. METHOD:
      We used survey data from 160 healthcare professionals working in Germany in the
      field of rare diseases, including physicians, caregivers, and therapists. A
      mediation model was statistically tested using linear multiple regression
      analysis. RESULTS: The existence of guidelines for operational processes
      contributes to innovative work behavior by integrating the stages of knowledge
      acquisition, idea generation, and solution implementation. Individuals'
      flexibility in their role ownership mediates this relationship. In addition, we
      found evidence that physicians are more active in acquiring knowledge, whereas
      nurses or therapists show more initiative in generating new ideas. CONCLUSION:
      Engaging in different roles enables healthcare professionals to demonstrate
      initiative for innovative work behavior aside from the completion of their daily
      tasks. The assumption of new roles may be encouraged by the creation of overall
      guidelines that raise awareness for the workers' need to take on extra tasks and
      innovative behavior.

PMID- 22405487
TI  - Challenging Health in All Policies, an action research study in Dutch
      municipalities.
AB  - The Dutch government encourages municipalities to develop 'Health in All
      Policies' (HiAP). The development of such a policy requires inter-sectoral
      collaboration, however municipalities show little initiative in this regard.
      Operating in an advisory role, the regional Public Health Service (PHS) has
      supported municipalities in South-Limburg in setting up inter-sectoral
      collaboration. A coaching program for municipal stakeholders was developed and
      implemented to improve HiAP, using obesity as an example. To determine the
      effectiveness of this coaching program, civil servants, managers and municipal
      councilors were invited to fill in an Internet questionnaire prior to and at the
      completion of the program. By means of a log-book all activities were registered
      in coached municipalities and in-depth interviews were held with municipal
      managers. Outcomes were scored depending on the stage of HiAP proposals. Six of
      the nine coached municipalities showed concrete outcomes in terms of HiAP
      proposals. The results show that more support and involvement at each system
      level stimulates the development of HiAP. The program contributed positively to
      the implementation of HiAP interventions targeting obesity. The pretest results
      for coached municipalities were better compared to non-coached municipalities.
      However, after 30 months of coaching this positive starting position faded away.
      We recommend that the municipal management become more involved in the
      development of HiAP and advise the PHS to increasingly demonstrate their
      expertise. Here lies a challenge for municipalities and their regional PHS.

PMID- 22405488
TI  - Mortality caused by influenza and respiratory syncytial virus by age group in
      England and Wales 1999-2010.
AB  - BACKGROUND: The mortality burden caused by influenza cannot be quantified
      directly from death certificates because of under-recording; therefore, the
      estimated number of influenza deaths has to be obtained through statistical
      modelling. OBJECTIVE: To estimate the number of deaths caused by influenza and
      respiratory syncytial virus (RSV) in England and Wales between 1999 and 2010
      using a multivariable regression model. METHODS: Generalised linear models were
      used to estimate weekly deaths by age group (<15, 15-44, 45-74 and 75+ years) as
      a function of positive influenza and RSV isolates. Adjustment was made for
      temperature variation (using weekly means of daily Central England temperature
      time series), underlying seasonal variation and temporal trends. The parameters
      from the model were used to predict the number of deaths caused by influenza and
      RSV across winter seasons. RESULTS: Between 7000 and 25 000 deaths across all
      ages were associated with influenza in the winter periods 1999-2009. The
      mortality burden was the highest among the over 75 age group, among whom 2.5-8.1%
      of deaths were caused by influenza. The lowest number of influenza deaths was
      estimated for the winter 2009/2010 when pandemic influenza A/H1N1 (2009) was the
      predominant circulating strain. RSV accounted for 5000-7500 deaths each winter
      season. CONCLUSIONS: The model presented provides a robust and reasonable
      approach to estimating the number of deaths caused by influenza and RSV by age
      group at the end of each winter.

PMID- 22405489
TI  - Sexual function in breast cancer patients: a prospective study from Iran.
AB  - BACKGROUND: Sexual function in patients with breast cancer especially in younger
      patients is an important issue from clinical and psychosocial perspectives. This
      study aimed to assess sexual function among Iranian breast cancer patients.
      METHODS: This was a prospective study of sexual function in breast cancer
      patients attending the Cancer Institute of Iran. Sexual function was assessed
      using the Female Sexual Function Index (FSFI) at two points in time: baseline
      (pre-treatment) and after completion of cancer treatment at follow-up visits
      (post-treatment). Pre- and post-treatment data were compared. In addition
      logistic regression analysis was performed to find out factors that contributing
      to post-treatment sexual dysfunction. RESULTS: In all 277 breast cancer patients
      were approached. Of these, 231 patients (83%) were sexually active and data for
      216 patients (93.5% of sexually active patients) were available at pre-and post
      treatment. Overall pre- and post-treatment sexual dysfunction was found to be 52%
      and 84%, respectively indicating a significant deterioration in sexual function
      among breast cancer patients. The results obtained from multiple logistic
      regression analysis indicated that younger age [OR = 0.95, 95% CI = 0.93-0.98; P
      = 0.04], receiving endocrine therapy [OR = 3.34, 95% CI = 1.37-7.91; P = 0.007]
      and poor sexual function at pre-treatment [OR = 12.3, 95% CI = 3.93-39.0; P <
      0.0001] were the most significant contributing factors to post-treatment sexual
      disorders. CONCLUSION: A significant number of breast cancer patients experience
      deterioration in sexual function over time. The findings from this study
      indicated that younger age, receiving endocrine therapy, and poor sexual function
      at diagnosis were the most significant predicting factors for sexual disorders
      following treatment.

PMID- 22405490
TI  - The effects of oral clefts on hospital use throughout the lifespan.
AB  - BACKGROUND: Oral clefts are one of the most common birth defects worldwide. They
      require multiple healthcare interventions and add significant burden on the
      health and quality of life of affected individuals. However, not much is known
      about the long term effects of oral clefts on health and healthcare use of
      affected individuals. In this study, we evaluate the effects of oral clefts on
      hospital use throughout the lifespan. METHODS: We estimate two-part regression
      models for hospital admission and length of stay for several age groups up to 68
      years of age. The study employs unique secondary population-based data from
      several administrative inpatient, civil registration, demographic and labor
      market databases for 7,670 individuals born with oral clefts between 1936 and
      2002 in Denmark, and 220,113 individuals without oral clefts from a 5% random
      sample of the total birth population from 1936 to 2002. RESULTS: Oral clefts
      significantly increase hospital use for most ages below 60 years by up to 233%
      for children ages 0-10 years and 16% for middle age adults. The more severe cleft
      forms (cleft lip with palate) have significantly larger effects on
      hospitalizations than less severe forms. CONCLUSIONS: The results suggest that
      individuals with oral clefts have higher hospitalization risks than the general
      population throughout most of the lifespan.

PMID- 22405491
TI  - Effect of delayed umbilical cord clamping on blood gas analysis.
AB  - OBJECTIVE: To ascertain if there are differences in umbilical cord blood gas
      analysis between immediate and delayed cord clamping. STUDY DESIGN: In a
      prospective observational study on 60 vaginally delivered healthy term newborns,
      we sampled umbilical cord blood immediately after delivery and at the time
      umbilical cord pulsation spontaneously ceased. RESULTS: There were significant
      decreases in pH, oxygen saturation (sO(2)), glycemia, oxygen content (ctO(2)),
      bicarbonate (HCO(3)(-)) and base excess (BE). Lactate and  [Formula: see text] 
      increased. Delayed cord clamping pH correlated with immediate cord clamping pH, 
      [Formula: see text] , ctHb, sO(2) and time (r(2)=0.77, p<0.000). Delayed cord
      clamping lactate was associated with immediate cord clamping lactate and time
      (r(2)=0.83, p<0.000). Delayed BE was associated with previous pH, lactate,
      glycemia, ctHb and time (r(2)=0.83, p<0.000). CONCLUSIONS: Delayed cord clamping
      alters acid-base parameters and lactate values compared to immediate cord
      clamping. Those variations depend mainly on time, prior pH and lactate.

PMID- 22405492
TI  - Characterization of Neisseria meningitidis isolates from Egypt using multilocus
      sequence typing.
AB  - To characterize Neisseria meningitidis isolates collected from cerebrospinal
      fluid of meningitis cases in Egypt (1998-2003) as part of surveillance studies,
      67 isolates were serogrouped, tested for antibiotic sensitivity and analyzed
      using multilocus sequence typing (MLST). Results show that isolates expressing
      serogroup B (50.7%) and serogroup A (34.3%) antigens were predominant in Egypt
      during the surveillance period, possibly due to suppression of other serogroups
      by meningococcal vaccines in current use. Intermediate resistance to penicillin
      was observed in 71% of the isolates, suggesting a need for physicians to shift to
      third-generation cephalosporins during the empirical treatment of infection.
      Recurrent lineages of N. meningitidis in Egypt appear to originate from Europe
      and other Middle Eastern countries. Of 19 sequence types detected, five were
      unique to Africa and 10 were not observed previously in the MLST database. The
      information obtained illustrates the changing dynamics of meningitis after
      vaccine introduction in Egypt.

PMID- 22405493
TI  - Early detection of children at risk for antisocial behaviour using data from
      routine preventive child healthcare.
AB  - BACKGROUND: Youth antisocial behaviour is highly prevalent. Young people are
      usually not willing to disclose such behaviour to professionals and parents. Our
      aim was to assess whether child health professionals (CHP) working in preventive
      child healthcare could identify pre-adolescents at risk for antisocial behaviour
      through using data that they obtain in routine practice. METHODS: CHPs examined a
      national sample of 974 pre-adolescents aged 8-12 years (response 79.1%), and
      interviewed parents and children during routine well-child assessments. We
      obtained data on family background and current health of the child from the CHP;
      on developmental concerns from parents, and on social and emotional well-being,
      injuries, and substance use from the children. Antisocial behaviour concerned the
      adolescent-reported 15 item International Self-Reported Delinquency study
      questionnaire, among which are 5 items on violence against people. RESULTS: The
      prevalence of 2+acts of any antisocial behaviour was 21.8%, and 33.9% for 1+acts
      of violence (10.5% for 2+). Children who were male, had a young mother, no parent
      employed, recent injuries, poor performance at school or who were bored by
      school, and who had parental concerns more often reported 2+antisocial acts and
      1+violence against people. Detection algorithms on the basis of these variables
      were moderately able to classify outcomes, with Areas-Under-the-Curves ranging
      from 0.66 to 0.71. CONCLUSIONS: Data from routine well-child assessment can help
      CHPs to detect pre-adolescents at risk for antisocial behaviour, but detection
      algorithms need to be further improved. This could be done by obtaining
      additional information on factors that are associated with antisocial behaviour.

PMID- 22405494
TI  - Development and evaluation of multiple tendon injury models in the mouse.
AB  - The mouse has proven to be an advantageous animal model system in basic science
      research focused on aiding in development and evaluation of potential treatments;
      however, the small size of mouse tendons makes consistent and reproducible injury
      models and subsequent biomechanical evaluation challenging for studying tendon
      healing. In this study, we investigated the feasibility and reproducibility of
      multiple mouse tendon injury models. Our hypothesis was that incisional (using a
      blade) and excisional (using a biopsy punch) injuries would result in consistent
      differences in tendon material properties. At 16 weeks of age, 17 C57BL/6 mice
      underwent surgery to create defects in the flexor digitorum longus, Achilles, or
      patellar tendon. Each animal received 1-2 full-thickness, central-width
      incisional or excisional injuries per limb; at least one tendon per limb remained
      uninjured. The injuries were distributed such that each tendon type had
      comparable numbers of uninjured, incisionally injured, and excisionally injured
      specimens. Three weeks after injury, all animals were euthanized and tendons were
      harvested for mechanical testing. As hypothesized, differences were detected for
      all three different tendon types at three weeks post-injury. While all models
      created injuries that produced predictable outcomes, the patellar tendon model
      was the most consistent in terms of number and size of significant differences in
      injured tendons compared to native properties, as well as in the overall variance
      in the data. This finding provides support for its use in fundamental tendon
      healing studies; however, future work may use any of these models, based on their
      appropriateness for the specific question under study.

PMID- 22405495
TI  - Sensitivity of maximum sprinting speed to characteristic parameters of the muscle
      force-velocity relationship.
AB  - An accumulation of evidence suggests that the force-velocity relationship (FVR)
      of skeletal muscle plays a major role in limiting maximum human sprinting speed.
      However, most of the theories on this limiting role have been non-specific as to
      how the FVR limits speed. The FVR is characterized by three parameters that each
      have a different effect on its shape, and could thus limit sprinting speed in
      different ways: the maximum shortening velocity V(max), the shape parameter A(R),
      and the eccentric plateau C(ecc). In this study, we sought to determine how
      specifically the FVR limits sprinting speed using forward dynamics simulations of
      human locomotion to examine the sensitivity of maximum speed to these three FVR
      parameters. Simulations were generated by optimizing the model's muscle
      excitations to maximize the average horizontal speed. The simulation's speed,
      temporal stride parameters, joint angles, GRF, and muscle activity in general
      compared well to data from human subjects sprinting at maximum effort.
      Simulations were then repeated with incremental and isolated adjustments in
      V(max), A(R), and C(ecc) across a physiological range. The range of speeds (5.22
      6.91 m s-1) was most sensitive when V(max) was varied, but the fastest speed of
      7.17 m s-1 was attained when A(R) was set to its maximum value, which
      corresponded to all muscles having entirely fast-twitch fibers. This result was
      explained by the muscle shortening velocities, which tended to be moderate and
      within the range where A(R) had its greatest effect on the shape of the FVR.
      Speed was less sensitive to adjustments in C(ecc), with a range of 6.23-6.70 m s
      1. Increases in speed with parameter changes were due to increases in stride
      length more so than stride frequency. The results suggest that the shape
      parameter A(R), which primarily determines the amount of muscle force that can be
      produced at moderate shortening velocities, plays a major role in limiting the
      maximum sprinting speed. Analysis of muscle force sensitivity indicated support
      for previous theories on the time to generate support forces in stance (Weyand et
      al., 2000, Journal of Applied Physiology, 89, 1991-1999) and energy management of
      the leg in swing (Chapman & Caldwell, 1983, Journal of Biomechanics 16, 79-83) as
      important factors in limiting maximum speed. However, the ability of the knee
      flexors to slow the rotational velocity of the leg in preparation for footstrike
      did not appear to play a major role in limiting speed.

PMID- 22405496
TI  - A least-squares identification algorithm for estimating squat exercise mechanics
      using a single inertial measurement unit.
AB  - This study investigated the possibility of estimating lower-limb joint kinematics
      during a squat exercise performed in the sagittal plane based on data collected
      from a single inertial measurement unit located on the lower trunk. The human
      body was modeled as a three-degrees-of-freedom planar chain and the relevant
      joint angles (ankle, knee, and hip) are represented by Fourier series. A least
      squares approach based on the minimization of the difference between the measured
      and estimated linear accelerations and the angular velocity of the lower trunk
      was used to solve the related analytical problem. The approach was validated on
      ten healthy young volunteers (ten trials each) using a force plate and a
      stereophotogrammetric system to collect reference data. The root mean square
      differences between the estimated joint angles and those reconstructed with the
      stereophotogrammetric system were lower than 4 degrees  with correlation
      coefficients higher than 0.99. The ankle joint resultant vertical force component
      was estimated with an accuracy of about 3% and a high correlation coefficient of
      r=0.95, whereas much lower percentage accuracies were found for the horizontal
      force and couple components. The latter accuracies were similar to those
      affecting these force and couple components as estimated through inverse dynamics
      and the stereophotogrammetric data in conjunction with the same mechanical model,
      which suggests that only minor errors were introduced by the proposed algorithm
      and measurement tools.

PMID- 22405497
TI  - Effective property of tooth enamel: monoclinic behavior.
AB  - Human tooth enamel possesses a unique morphology characterized by a repeated cell
      arrangement, which is composed of varying orientations of hydroxyapatite
      crystals. In the past, various investigators have reported diverse mechanical
      properties based on isotropic or orthotropic mechanical models in their
      experimental and numerical studies. However, these models are insufficient to
      capture the accurate microstructural effects on the enamel mechanical response.
      In this paper, a monoclinic anisotropic model, which offers correct descriptions
      of enamel deformation behaviors, is introduced. The model takes into account the
      3D orientation changes of the hydroxyapatite crystals and their spatial elastic
      property variations. The proposed approach is based on a unit-cell and periodic
      boundary conditions, and it utilizes the collective deformation characteristics
      of many rods to determine 13 independent material constants required for the
      monoclinic model. These constants are necessary to utilize the effective property
      model to study various mechanical conditions such as abrasion, erosion, wear and
      fracture of whole tooth enamel.

PMID- 22405498
TI  - Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia
      induced cell death in rat cerebellar granule cells.
AB  - BACKGROUND: Episodic cessation of airflow during sleep in patients with sleep
      apnea syndrome results in intermittent hypoxia (IH). Our aim was to investigate
      the effects of IH on cerebellar granule cells and to identify the mechanism of IH
      induced cell death. METHODS: Cerebellar granule cells were freshly prepared from
      neonatal Sprague-Dawley rats. IH was created by culturing the cerebellar granule
      cells in the incubators with oscillating O2 concentration at 20% and 5% every 30
      min for 1-4 days. The results of this study are based on image analysis using a
      confocal microscope and associated software. Cellular oxidative stress increased
      with increase in IH. In addition, the occurrence of cell death (apoptosis and
      necrosis) increased as the duration of IH increased, but decreased in the
      presence of an iron chelator (phenanthroline) or poly (ADP-ribose) polymerase
      (PARP) inhibitors [3-aminobenzamide (3-AB) and DPQ]. The fluorescence of caspase
      3 remained the same regardless of the duration of IH, and Western blots did not
      detect activation of caspase-3. However, IH increased the ratio of apoptosis
      inducing factor (AIF) translocation to the nucleus, while PARP inhibitors (3-AB)
      reduced this ratio. RESULTS: According to our findings, IH increased oxidative
      stress and subsequently leading to cell death. This effect was at least partially
      mediated by PARP activation, resulting in ATP depletion, calpain activation
      leading to AIF translocation to the nucleus. CONCLUSIONS: We suggest that IH
      induces cell death in rat primary cerebellar granule cells by stimulating
      oxidative stress PARP-mediated calpain and AIF activation.

PMID- 22405499
TI  - Atomoxetine treatment for nicotine withdrawal: a pilot double-blind, placebo
      controlled, fixed-dose study in adult smokers.
AB  - BACKGROUND: Many effective treatments for nicotine addiction inhibit
      noradrenaline reuptake. Three recent studies have suggested that another
      noradrenaline reuptake inhibitor, atomoxetine, may reduce smoking behaviors.
      METHODS: The present double-blind, placebo-controlled, fixed-dose study was
      carried out over 21 days during which administration of 40 mg atomoxetine was
      compared to placebo in 17 individuals. Of these, nine were randomized to
      atomoxetine and eight to placebo. Baseline and weekly measurements were made
      using the Cigarette Dependence Scale (CDS), Cigarette Withdrawal Scale (CWS),
      Questionnaire of Smoking Urges (QSU), reported number of cigarettes smoked, and
      salivary cotinine levels. RESULTS: The study results showed that all those on
      placebo completed the study. In marked contrast, of the nine individuals who
      started on atomoxetine, five dropped out due to side effects. In a completer
      analysis there were statistically significant differences at 14 and 21 days in
      several measures between the atomoxetine and placebo groups, including CDS, CWS,
      QSU, number of cigarettes smoked (decreasing to less than two per day in the
      treatment group who completed the study), and a trend towards lower mean salivary
      cotinine levels. However, these differences were not seen in a last observation
      carried forward (LOCF) analysis. CONCLUSIONS: In summary, this is the first study
      to examine the use of atomoxetine in non-psychiatric adult smokers for a period
      of more than 7 days, and the findings suggest that atomoxetine might be a useful
      treatment for nicotine addiction. However, the dose used in the current study was
      too high to be tolerated by many adults, and a dose-finding study is required to
      determine the most appropriate dose for future studies of this potential
      treatment for smoking cessation.

PMID- 22405500
TI  - Shared decision making through informed consent in chiropractic management of low
      back pain.
AB  - OBJECTIVE: The purpose of this study was to propose questions that may be helpful
      to educate patients considering treatment approaches to manage low back pain
      (LBP) and to determine if the information currently presented in informed consent
      (IC) documents at chiropractic colleges is sufficient to help a patient
      considering chiropractic management of LBP make a fully informed decision.
      METHODS: Questions to inform decision making for a patient contemplating any
      intervention for LBP were developed by the authors based on their clinical and
      research experience. Answers to the questions were suggested based on findings
      from recent clinical practice guidelines and systematic reviews. Institutions
      that are members of the Association of Chiropractic Colleges (ACC) were surveyed
      and asked to provide a copy of the IC documents currently used in their
      outpatient educational clinics. The IC documents were analyzed to determine if
      they stated (or implied) information that may be helpful in addressing each of
      the proposed questions. RESULTS: The list of 20 questions included 4 questions on
      each of the following 5 topics: condition, proposed treatment, potential
      benefits, potential harms, and possible alternatives. A total of 21 ACC
      institutions were contacted, of which 20 responded. The number of questions that
      could potentially be answered with information provided in the IC documents
      ranged from 2 to 13, with a mean of 6.5, including a mean of 3.6 stated answers
      and 2.9 implied answers. CONCLUSIONS: Some information to help patients consider
      chiropractic management of LBP is currently included in the IC documents used in
      clinics of ACC institutions. However, many of the questions that could help
      achieve shared decision making are not included. Modifying IC documents may help
      patients understand the nature, benefits, harms, costs, and alternatives to LBP
      care.

PMID- 22405501
TI  - Assessment of nonverbal communication in clinical encounters: many methodological
      approaches, but no gold standard.

PMID- 22405503
TI  - Medetomidine continuous rate intravenous infusion in horses in which surgical
      anaesthesia is maintained with isoflurane and intravenous infusions of lidocaine
      and ketamine.
AB  - OBJECTIVE: To evaluate medetomidine as a continuous rate infusion (CRI) in horses
      in which anaesthesia is maintained with isoflurane and CRIs of ketamine and
      lidocaine. STUDY DESIGN: Prospective, randomized, blinded clinical trial.
      ANIMALS: Forty horses undergoing elective surgery. METHODS: After sedation and
      induction, anaesthesia was maintained with isoflurane. Mechanical ventilation was
      employed. All horses received lidocaine (1.5 mg kg(-1) initially, then 2 mg kg(
      1) hour(-1)) and ketamine (2 mg kg(-1) hour(-1)), both CRIs reducing to 1.5 mg
      kg(-1) hour(-1) after 50 minutes. Horses in group MILK received a medetomidine
      CRI of 3.6 MUg kg(-1) hour(-1), reducing after 50 minutes to 2.75 MUg kg(-1)
      hour(-1), and horses in group ILK an equal volume of saline. Mean arterial
      pressure (MAP) was maintained above 70 mmHg using dobutamine. End-tidal
      concentration of isoflurane (FE'ISO) was adjusted as necessary to maintain
      surgical anaesthesia. Group ILK received medetomidine (3 MUg kg(-1) ) at the end
      of the procedure. Recovery was evaluated. Differences between groups were
      analysed using Mann-Whitney, Chi-Square and anova tests as relevant. Significance
      was taken as p < 0.05. RESULTS: FE'ISO required to maintain surgical anaesthesia
      in group MILK decreased with time, becoming significantly less than that in group
      ILK by 45 minutes. After 60 minutes, median (IQR) FE'ISO in MILK was 0.65 (0.4
      1.0) %, and in ILK was 1 (0.62-1.2) %. Physiological parameters did not differ
      between groups, but group MILK required less dobutamine to support MAP. Total
      recovery times were similar and recovery quality good in both groups. CONCLUSION
      AND CLINICAL RELEVANCE: A CRI of medetomidine given to horses which were also
      receiving CRIs of lidocaine and ketamine reduced the concentration of isoflurane
      necessary to maintain satisfactory anaesthesia for surgery, and reduced the
      dobutamine required to maintain MAP. No further sedation was required to provide
      a calm recovery.

PMID- 22405502
TI  - Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X
      syndrome mouse model.
AB  - Fragile X syndrome (FXS), the most common inherited form of intellectual
      disability and prevailing known genetic basis of autism, is caused by an
      expansion in the Fmr1 gene that prevents transcription and translation of fragile
      X mental retardation protein (FMRP). FMRP binds to and controls translation of
      mRNAs downstream of metabotropic glutamate receptor (mGluR) activation. Recent
      work shows that FMRP interacts with the transcript encoding striatal-enriched
      protein tyrosine phosphatase (STEP; Ptpn5). STEP opposes synaptic strengthening
      and promotes synaptic weakening by dephosphorylating its substrates, including
      ERK1/2, p38, Fyn and Pyk2, and subunits of N-methyl-d-aspartate (NMDA) and AMPA
      receptors. Here, we show that basal levels of STEP are elevated and mGluR
      dependent STEP synthesis is absent in Fmr1(KO) mice. We hypothesized that the
      weakened synaptic strength and behavioral abnormalities reported in FXS may be
      linked to excess levels of STEP. To test this hypothesis, we reduced or
      eliminated STEP genetically in Fmr1(KO) mice and assessed mice in a battery of
      behavioral tests. In addition to attenuating audiogenic seizures and seizure
      induced c-Fos activation in the periaqueductal gray, genetically reducing STEP in
      Fmr1(KO) mice reversed characteristic social abnormalities, including approach,
      investigation and anxiety. Loss of STEP also corrected select nonsocial anxiety
      related behaviors in Fmr1(KO) mice, such as light-side exploration in the
      light/dark box. Our findings indicate that genetically reducing STEP
      significantly diminishes seizures and restores select social and nonsocial
      anxiety-related behaviors in Fmr1(KO) mice, suggesting that strategies to inhibit
      STEP activity may be effective for treating patients with FXS.

PMID- 22405504
TI  - Cardiovascular morbidity, mortality and pharmacotherapy in patients with
      schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia have excess cardiovascular morbidity and
      mortality. Previous studies suggest that this may be partly due to inadequate
      somatic treatment and care, such as non-optimal use of lipid-lowering and
      antihypertensive pharmacotherapy, but longitudinal studies on such aetiological
      pathways are scarce. METHOD: We investigated the use of lipid-lowering and
      antihypertensive pharmacotherapy, and the risk of hospitalization for and death
      from coronary heart disease and stroke among patients with schizophrenia in a
      birth cohort of 12 939 subjects (Helsinki Birth Cohort Study). This cohort was
      followed for over 30 adult years by using national databases on cardio- and
      cerebrovascular hospitalizations and mortality and on reimbursement entitlements
      and use of drugs for treatment of hypertension, dyslipidaemia, coronary heart
      disease and diabetes. RESULTS: Individuals with schizophrenia had a higher risk
      of hospitalization for coronary heart disease [hazard ratio (HR) 1.65, 95%
      confidence interval (CI) 1.03-2.57], and mortality from this disease was markedly
      higher (HR 2.92, 95% CI 1.70-5.00), particularly among women (p=0.001 for women,
      p=0.008 for men). Women with schizophrenia had also marginally increased stroke
      mortality (p=0.06). However, patients with schizophrenia used less lipid-lowering
      (odds ratio 0.47, 95% CI 0.27-0.80) and antihypertensive drug treatment (HR 0.37,
      95% CI 0.22-0.61). CONCLUSIONS: In this longitudinal study, coronary heart
      disease morbidity was increased and coronary heart disease mortality markedly
      increased in patients, especially in women with schizophrenia. These patients
      nevertheless received less antihypertensive and lipid-lowering treatment.

PMID- 22405505
TI  - Risk and protective factors for depression symptoms among children affected by
      HIV/AIDS in rural China: a structural equation modeling analysis.
AB  - Previous research has revealed a negative impact of orphanhood and HIV-related
      stigma on the psychological well-being of children affected by HIV/AIDS. Little
      is known about psychological protective factors that can mitigate the effect of
      orphanhood and HIV-related stigma on psychological well-being. This research
      examines the relationships among several risk and protective factors for
      depression symptoms using structural equation modeling. Cross-sectional data were
      collected from 755 AIDS orphans and 466 children of HIV-positive parents aged 6
      18 years in 2006-2007 in rural central China. Participants reported their
      experiences of traumatic events, perceived HIV-related stigma, perceived social
      support, future orientation, trusting relationships with current caregivers, and
      depression symptoms. We found that the experience of traumatic events and HIV
      related stigma had a direct contributory effect on depression among children
      affected by HIV/AIDS. Trusting relationships together with future orientation and
      perceived social support mediated the effects of traumatic events and HIV-related
      stigma on depression. The final model demonstrated a dynamic interplay among
      future orientation, perceived social support and trusting relationships. Trusting
      relationships was the most proximate protective factor for depression. Perceived
      social support and future orientation were positively related to trusting
      relationships. We conclude that perceived social support, trusting relationships,
      and future orientation offer multiple levels of protection that can mitigate the
      effect of traumatic events and HIV-related stigma on depression. Trusting
      relationships with caregivers provides the most immediate source of psychological
      support. Future prevention interventions seeking to improve psychological well
      being among children affected by HIV/AIDS should attend to these factors.

PMID- 22405506
TI  - Individual- and area-level unemployment influence smoking cessation among African
      Americans participating in a randomized clinical trial.
AB  - African Americans suffer disproportionately from the adverse health consequences
      of smoking, and also report substantially lower socioeconomic status than Whites
      and other racial/ethnic groups in the U.S. Although socioeconomic disadvantage is
      known to have a negative influence on smoking cessation rates and overall health,
      little is known about the influence of socioeconomic status on smoking cessation
      specifically among African Americans. Thus, the purpose of the current study was
      to characterize the impact of several individual- and area-level indicators of
      socioeconomic status on smoking cessation among African Americans. Data were
      collected as part of a smoking cessation intervention study for African American
      smokers (N = 379) recruited from the Houston, Texas, metropolitan area, who
      participated in the study between 2005 and 2007. The separate and combined
      influences of individual-level (insurance status, unemployment, education, and
      income) and area-level (neighborhood unemployment, education, income, and
      poverty) indicators of socioeconomic status on continuous smoking abstinence were
      examined across time intervals using continuation ratio logit modeling.
      Individual-level analyses indicated that unemployment was significantly
      associated with reduced odds of smoking abstinence, while higher income was
      associated with greater odds of abstinence. However, only unemployment remained a
      significant predictor of abstinence when unemployment and income were included in
      the model together. Area-level analyses indicated that greater neighborhood
      unemployment and poverty were associated with reduced odds of smoking abstinence,
      while greater neighborhood education was associated with higher odds of
      abstinence. However, only neighborhood unemployment remained significantly
      associated with abstinence status when individual-level income and unemployment
      were included in the model. Overall, findings suggest that individual- and area
      level unemployment have a negative impact on smoking cessation among African
      Americans. Addressing unemployment through public policy and within smoking
      cessation interventions, and providing smoking cessation treatment for the
      unemployed may have a beneficial impact on tobacco-related health disparities.

PMID- 22405507
TI  - Indicators of the need for ICU admission following suicide bombing attacks.
AB  - INTRODUCTION: Critical hospital resources, especially the demand for ICU beds,
      are usually limited following mass casualty incidents such as suicide bombing
      attacks (SBA). Our primary objective was to identify easily diagnosed external
      signs of injury that will serve as indicators of the need for ICU admission. Our
      secondary objective was to analyze under- and over-triage following suicidal
      bombing attacks. METHODS: A database was collected prospectively from patients
      who were admitted to Hadassah University Hospital Level I Trauma Centre,
      Jerusalem, Israel from August 2001-August 2005 following a SBA. One hundred and
      sixty four victims of 17 suicide bombing attacks were divided into two groups
      according to ICU and non-ICU admission. RESULTS: There were 86 patients in the
      ICU group (52.4%) and 78 patients in the non-ICU group (47.6%). Patients in the
      ICU group required significantly more operating room time compared with patients
      in the non-ICU group (59.3% vs. 25.6%, respectively, p=0.0003). For the ICU
      group, median ICU stay was 4 days (IQR 2 to 8.25 days). On multivariable analysis
      only the presence of facial fractures (p=0.014), peripheral vascular injury
      (p=0.015), injury>=4 body areas (p=0.002) and skull fractures (p=0.017) were
      found to be independent predictors of the need for ICU admission. Sixteen
      survivors (19.5%) in the ICU group were admitted to the ICU for one day only (ICU
      LOS=1) and were defined as over-triaged. Median ISS for this group was
      significantly lower compared with patients who were admitted to the ICU for >1
      day (ICU-LOS>1). This group of over-triaged patients could not be distinguished
      from the other ICU patients based on external signs of trauma. None of the
      patients in the non-ICU group were subsequently transferred to the ICU.
      CONCLUSIONS: Our results show that following SBA, injury to >=4 areas, and
      certain types of injuries such as facial and skull fractures, and peripheral
      vascular injury, can serve as surrogates of severe trauma and the need for ICU
      admission. Over-triage rates following SBA can be limited by a concerted, focused
      plan implemented by dedicated personnel and by the liberal utilization of imaging
      studies.

PMID- 22405508
TI  - Mucosal antibody responses are directed by viral burden in children with acute
      influenza infection.
AB  - BACKGROUND: Influenza infection causes excess hospitalizations and deaths in
      younger patients, but susceptibility to severe disease is poorly understood.
      While mucosal antibodies can limit influenza-associated infection and disease,
      little is known about acute mucosal antibody responses to influenza infection.
      OBJECTIVES: These studies characterize mucosal antiviral antibody production in
      children during lower respiratory infection (LRI) with H1N1 influenza versus
      other viral LRI and examine the relationship between mucosal antiviral antibodies
      and protection against severe disease. METHODS: B lymphocytes were assessed by
      immunohistochemistry in lung tissue from infants with fatal acute seasonal
      influenza infection. Nasopharyngeal secretions (NPS) were obtained at
      presentation from children with acute respiratory illness, including H1N1 (2009)
      influenza infection. Total and antiviral antibodies, and inflammatory and immune
      mediators, were quantified by ELISA. Neutralizing activity in NPS was detected
      using a pseudotyped virus assay. Viral burden was assessed by qPCR. RESULTS AND
      CONCLUSIONS: B lymphocytes were abundant in lung tissue of infants with fatal
      acute influenza LRI. Among surviving children with H1N1 infection, only a small
      subset (11%) demonstrated H1N1 neutralizing activity in NPS. H1N1 neutralizing
      activity coincided with high local levels of antiviral IgM, IgG and IgA, greater
      detection of inflammatory mediators, and higher viral burden (P = 0.016).
      Patients with mucosal antiviral antibody responses demonstrated more severe
      respiratory symptoms including greater hypoxia (P = 0.0018) and pneumonia (P =
      0.038). These patients also trended toward younger age, longer duration of
      illness and longer hospital stays. Prophylaxis strategies that heighten
      neutralizing antibody production in the mucosa are likely to benefit both older
      and younger children.

PMID- 22405509
TI  - Positive surgical margin and perioperative complication rates of primary surgical
      treatments for prostate cancer: a systematic review and meta-analysis comparing
      retropubic, laparoscopic, and robotic prostatectomy.
AB  - CONTEXT: Radical prostatectomy (RP) approaches have rarely been compared
      adequately with regard to margin and perioperative complication rates. OBJECTIVE:
      Review the literature from 2002 to 2010 and compare margin and perioperative
      complication rates for open retropubic RP (ORP), laparoscopic RP (LRP), and robot
      assisted LRP (RALP). EVIDENCE ACQUISITION: Summary data were abstracted from 400
      original research articles representing 167,184 ORP, 57,303 LRP, and 62,389 RALP
      patients (total: 286,876). Articles were found through PubMed and Scopus searches
      and met a priori inclusion criteria (eg, surgery after 1990, reporting margin
      rates and/or perioperative complications, study size>25 cases). The primary
      outcomes were positive surgical margin (PSM) rates, as well as total intra- and
      perioperative complication rates. Secondary outcomes included blood loss,
      transfusions, conversions, length of hospital stay, and rates for specific
      individual complications. Weighted averages were compared for each outcome using
      propensity adjustment. EVIDENCE SYNTHESIS: After propensity adjustment, the LRP
      group had higher positive surgical margin rates than the RALP group but similar
      rates to the ORP group. LRP and RALP showed significantly lower blood loss and
      transfusions, and a shorter length of hospital stay than the ORP group. Total
      perioperative complication rates were higher for ORP and LRP than for RALP. Total
      intraoperative complication rates were low for all modalities but lowest for
      RALP. Rates for readmission, reoperation, nerve, ureteral, and rectal injury,
      deep vein thrombosis, pneumonia, hematoma, lymphocele, anastomotic leak, fistula,
      and wound infection showed significant differences between groups, generally
      favoring RALP. The lack of randomized controlled trials, use of margin status as
      an indicator of oncologic control, and inability to perform cost comparisons are
      limitations of this study. CONCLUSIONS: This meta-analysis demonstrates that RALP
      is at least equivalent to ORP or LRP in terms of margin rates and suggests that
      RALP provides certain advantages, especially regarding decreased adverse events.

PMID- 22405510
TI  - A systematic review and meta-analysis on the use of phosphodiesterase 5
      inhibitors alone or in combination with alpha-blockers for lower urinary tract
      symptoms due to benign prostatic hyperplasia.
AB  - CONTEXT: Several randomized controlled trials (RCTs) on phosphodiesterase type 5
      inhibitors (PDE5-Is) have showed significant improvements in both lower urinary
      tract symptoms (LUTS) and erectile dysfunction (ED) in men affected by one or
      both conditions, without a significant increase in adverse events. However, the
      results are inconsistent. OBJECTIVE: Perform a systematic review and meta
      analysis of available prospective and cross-sectional studies on the use of PDE5
      Is alone or in combination with alpha1-adrenergic blockers in patients with
      LUTS/benign prostatic hyperplasia (BPH). EVIDENCE ACQUISITION: A systematic
      search was performed using the Medline, Embase, and Cochrane Library databases
      through September 2011 including the combination of the following terms: LUTS,
      BPH, PDE5-Is, sildenafil, tadalafil, vardenafil, udenafil, alpha-blockers, and
      alpha1-adrenergic blocker. The meta-analysis was conducted according to the
      guidelines for observational studies in epidemiology. EVIDENCE SYNTHESIS: Of 107
      retrieved articles, 12 were included in the present meta-analysis: 7 on PDE5-Is
      versus placebo, with 3214 men, and 5 on the combination of PDE5-Is with alpha1
      adrenergic blockers versus alpha1-adrenergic blockers alone, with 216 men. Median
      follow-up of all RCTs was 12 wk. Combining the results of those trials, the use
      of PDE5-Is alone was associated with a significant improvement of the
      International Index of Erectile Function (IIEF) score (+5.5; p<0.0001) and
      International Prostate Symptom Score (IPSS) (-2.8; p<0.0001) but not the maximum
      flow rate (Q(max)) (-0.00; p=not significant) at the end of the study as compared
      with placebo. The association of PDE5-Is and alpha1-adrenergic blockers improved
      the IIEF score (+3.6; p<0.0001), IPSS score (-1.8; p = 0.05), and Q(max) (+1.5;
      p<0.0001) at the end of the study as compared with alpha-blockers alone.
      CONCLUSIONS: The meta-analysis of the available cross-sectional data suggests
      that PDE5-Is can significantly improve LUTS and erectile function in men with
      BPH. PDE5-Is seem to be a promising treatment option for patients with LUTS
      secondary to BPH with or without ED.

PMID- 22405512
TI  - Management of frozen shoulder: a systematic review and cost-effectiveness
      analysis.
AB  - BACKGROUND: Frozen shoulder is condition in which movement of the shoulder
      becomes restricted. It can be described as either primary (idiopathic) whereby
      the aetiology is unknown, or secondary, when it can be attributed to another
      cause. It is commonly a self-limiting condition, of approximately 1 to 3 years'
      duration, though incomplete resolution can occur. OBJECTIVES: To evaluate the
      clinical effectiveness and cost-effectiveness of treatments for primary frozen
      shoulder, identify the most appropriate intervention by stage of condition and
      highlight any gaps in the evidence. DATA SOURCES: A systematic review was
      conducted. Nineteen databases and other sources including the Cumulative Index to
      Nursing and Allied Health (CINAHL), Science Citation Index, BIOSIS Previews and
      Database of Abstracts of Reviews of Effects (DARE) were searched up to March 2010
      and EMBASE and MEDLINE up to January 2011, without language restrictions.
      MEDLINE, CINAHL and PsycINFO were searched in June 2010 for studies of patients'
      views about treatment. REVIEW METHODS: Randomised controlled trials (RCTs)
      evaluating physical therapies, arthrographic distension, steroid injection,
      sodium hyaluronate injection, manipulation under anaesthesia, capsular release or
      watchful waiting, alone or in combination were eligible for inclusion. Patients
      with primary frozen shoulder (with or without diabetes) were included. Quasi
      experimental studies were included in the absence of RCTs and case series for
      manipulation under anaesthesia (MUA) and capsular release only. Full economic
      evaluations meeting the intervention and population inclusion criteria of the
      clinical review were included. Two researchers independently screened studies for
      relevance based on the inclusion criteria. One reviewer extracted data and
      assessed study quality; this was checked by a second reviewer. The main outcomes
      of interest were pain, range of movement, function and disability, quality of
      life and adverse events. The analysis comprised a narrative synthesis and pair
      wise meta-analysis. A mixed-treatment comparison (MTC) was also undertaken. An
      economic decision model was intended, but was found to be implausible because of
      a lack of available evidence. Resource use was estimated from clinical advisors
      and combined with quality-adjusted life-years obtained through mapping to present
      tentative cost-effectiveness results. RESULTS: Thirty-one clinical effectiveness
      studies and one economic evaluation were included. The clinical effectiveness
      studies evaluated steroid injection, sodium hyaluronate, supervised neglect,
      physical therapy (mainly physiotherapy), acupuncture, MUA, distension and
      capsular release. Many of the studies identified were at high risk of bias.
      Because of variation in the interventions and comparators few studies could be
      pooled in a meta-analysis. Based on single RCTs, and for some outcomes only,
      short-wave diathermy may be more effective than home exercise. High-grade
      mobilisation may be more effective than low-grade mobilisation in a population in
      which most patients have already had treatment. Data from two RCTs showed that
      there may be benefit from adding a single intra-articular steroid injection to
      home exercise in patients with frozen shoulder of < 6 months' duration. The same
      two trials showed that there may be benefit from adding physiotherapy (including
      mobilisation) to a single steroid injection. Based on a network of nine studies
      the MTC found that steroid combined with physiotherapy was the only treatment
      showing a statistically and clinically significant beneficial treatment effect
      compared with placebo for short-term pain (standardised mean difference -1.58,
      95% credible interval -2.96 to -0.42). This analysis was based on only a subset
      of the evidence, which may explain why the findings are only partly supportive of
      the main analysis. No studies of patients' views about the treatments were
      identified. Average costs ranged from L36.16 for unguided steroid injections to
      L2204 for capsular release. The findings of the mapping suggest a positive
      relationship between outcome and European Quality of Life-5 Dimensions (EQ-5D)
      score: a decreasing visual analogue scale score (less pain) was accompanied by an
      increasing (better) EQ-5D score. The one published economic evaluation suggested
      that low-grade mobilisation may be more cost-effective than high-grade
      mobilisation. Our tentative cost-effectiveness analysis suggested that steroid
      alone may be more cost-effective than steroid plus physiotherapy or physiotherapy
      alone. These results are very uncertain. LIMITATIONS: The key limitation was the
      lack of data available. It was not possible to undertake the planned synthesis
      exploring the influence of stage of frozen shoulder or the presence of diabetes
      on treatment effect. As a result of study diversity and poor reporting of outcome
      data there were few instances where the planned quantitative synthesis was
      possible or appropriate. Most of the included studies had a small number of
      participants and may have been underpowered. The lack of available data made the
      development of a decision-analytic model implausible. We found little evidence on
      treatment related to stage of condition, treatment pathways, the impact on
      quality of life, associated resource use and no information on utilities. Without
      making a number of questionable assumptions modelling was not possible.
      CONCLUSIONS: There was limited clinical evidence on the effectiveness of
      treatments for primary frozen shoulder. The economic evidence was so limited that
      no conclusions can be made about the cost-effectiveness of the different
      treatments. High-quality primary research is required.

PMID- 22405513
TI  - Assessment of microbial larvicide spraying with Bacillus thuringiensis
      israelensis, for the prevention of malaria.
AB  - OBJECTIVES: The aim of this study was to assess the contribution of microbial
      larvicide spraying, Bacillus thuringiensis israelensis, as prevention strategy
      against malaria. METHODS: An experimental study consisted in spraying B.
      thuringiensis israelensis in a district during 1 year has been conducted. Another
      district (control) was not sprayed. Eight hundred and two children were
      evaluated, thick drop and swab examination was performed for those presenting
      with fever. The larval density was calculated in their habitats as well as
      larvicide remanence. Capture of mosquitoes with human bait allowed determining
      human exposure to bites at night, and identifying anopheles after dissection.
      RESULTS: The incidence of pediatric malaria was 13.8% in the sprayed district and
      31.4% in the control district. The parasitic load ranged from 2000 to 42,000
      parasites/MUL in the sprayed district and 2000 to 576,000 parasites/MUL in the
      control district. Plasmodium falciparum was the most frequent (97.8%) plasmodial
      species. In the control district, at least 20 larvae by liter of water were
      counted; anopheles larvae were found in 11 larval habitats out of 15 (73.33%).
      The human exposure to anopheles bites at night was 14.25 in the sprayed district
      and 33.13 in the control district. The remanence of B. thuringiensis israelensis
      was estimated at 9 days in the sprayed district. CONCLUSION: The larvicide B.
      thuringiensis israelensis may be used in vector control strategy for the
      prevention of malaria.

PMID- 22405514
TI  - [Asymptomatic and simultaneous fecal carriage of two strains of Escherichia coli
      expressing CTX-M-1 and CTX-M-14 extended-spectrum betalactamases].

PMID- 22405515
TI  - Automated analysis of sequence polymorphism in STR alleles by PCR and direct
      electrospray ionization mass spectrometry.
AB  - Short tandem repeats (STRs) are the primary genetic markers used for the analysis
      of biological samples in forensic and human identity testing. The discrimination
      power of a combination of STRs is sufficient in many human identity testing
      comparisons unless the evidence is substantially compromised and/or there are
      insufficient relatives or a potential mutation may have arisen in kinship
      analyses. An automated STR assay system that is based on electrospray ionization
      mass spectrometry (ESI-MS) has been developed that can increase the
      discrimination power of some of the CODIS core STR loci and thus provide more
      information in typical and challenged samples and cases. Data from the ESI-MS STR
      system is fully backwards compatible with existing STR typing results generated
      by capillary electrophoresis. In contrast, however, the ESI-MS analytical system
      also reveals nucleotide polymorphisms residing within the STR alleles. The
      presence of these polymorphisms expands the number of alleles at a locus.
      Population studies were performed on the 13 core CODIS STR loci from African
      Americans, Caucasians and Hispanics capturing both the length of the allele, as
      well as nucleotide variations contained within repeat motifs or flanking regions.
      Such additional polymorphisms were identified in 11 of the 13 loci examined
      whereby several nominal length alleles were subdivided. A substantial increase in
      heterozygosity was observed, with close to or greater than 5% of samples analyzed
      being heterozygous with equal-length alleles in at least one of five of the core
      CODIS loci. This additional polymorphism increases discrimination power
      significantly, whereby the seven most polymorphic STR loci have a discrimination
      power equivalent to the 10 most discriminating of the CODIS core loci. An
      analysis of substructure among the three population groups revealed a higher
      theta than would be observed compared with using alleles designated by nominal
      length, i.e., repeats solely. Two loci, D3S1358 and vWA produced theta estimates
      of 0.0477 and 0.0234, respectively, when the expanded allele complement (i.e.,
      nominal allele and SNPs) was considered compared to 0.0145 and 0.01266,
      respectively when only nominal repeat number was considered. These differences
      may indicate underlying population specific allele distributions exist within
      these populations. A system of nomenclature has been developed that facilitates
      the databasing, searching and analyses of these combined data forms.

PMID- 22405516
TI  - Evaluation and comparative analysis of direct amplification of STRs using
      PowerPlex(r) 18D and Identifiler(r) Direct systems.
AB  - Short tandem repeat (STR) analysis remains the primary forensic tool for DNA
      identification. Because of the success of forensic DNA typing and the use of
      database searches to develop investigative leads, there is an increased demand
      for populating forensic DNA databases. Reference samples tend to be of high
      quantity and quality and are somewhat standardized in format. Being more
      predictable in quality than unknown forensic casework samples, reference samples
      lend themselves to alternate methods of analysis such as direct amplification.
      Two commercially available direct amplification kits for processing reference
      samples were evaluated. The kits are PowerPlex((r)) 18D (Promega Corp., Madison,
      Wisconsin) and Identifiler((r)) Direct (Life Technologies, Carlsbad, CA). Both
      kits offer the core CODIS loci plus amelogenin, and the loci D2S1338, D19S433.
      The PP18D kit offers two additional loci, Penta E and Penta D. To determine the
      robustness and reliability of the PP18D and ID Direct amplification systems,
      buccal cell samples (deposited on FTA paper using the EasiCollectTM device
      (Florham Park, NJ)) from 400 anonymous donors were analyzed under conditions to
      achieve a high rate of successful typing. First-pass success rates were 96.25%,
      96.25%, and 95% for PP18D with a 5s injection, ID Direct with a 10s injection,
      and ID Direct with a 5s injection, respectively. Profiles that could not be typed
      were not a result of the kits' performance but were a result of the inherent
      variation in the amount of DNA obtained with the collection device and buccal
      cells. Low signal profiles can be re-analyzed by either re-injecting for a longer
      time or by re-amplification with an additional PCR cycle. Overloaded profiles can
      be re-analyzed by re-injecting for a shorter time or by re-amplification with one
      less cycle. All called typing results, when interpretable, were consistent under
      the prescribed conditions, different injection times, and 26-28 PCR cycles for
      both chemistries. Peak height ratios for both kits were well balanced with peaks
      ranging in height >2000 RFUs to those with one or more peaks with heights <100
      RFUs. A change in the ILS morphology sloping downward to the right relative to a
      normal ILS profile for PP18D and ID Direct was an indication of a poor injection.
      Re-injection effectively overcame the effect manifested by a sloping ILS
      phenomenon. A subset of samples were subjected to direct amplification using the
      reagents in Identifiler((r)) Plus kit and successful typing results were obtained
      for the majority of samples. However, the profiles displayed increased amounts of
      non-adenylated products. The results of this study demonstrate that PP18D and ID
      Direct are both robust kits for direct amplification. The interpretation
      guidelines used for this study can form a basis for internal validation studies
      by databasing laboratories.

PMID- 22405517
TI  - Performance of Identifiler Direct and PowerPlex 16 HS on the Applied Biosystems
      3730 DNA Analyzer for processing biological samples archived on FTA cards.
AB  - Direct amplification of STR loci from biological samples collected on FTA cards
      without prior DNA purification was evaluated using Identifiler Direct and
      PowerPlex 16 HS in conjunction with the use of a high throughput Applied
      Biosystems 3730 DNA Analyzer. In order to reduce the overall sample processing
      cost, reduced PCR volumes combined with various FTA disk sizes were tested.
      Optimized STR profiles were obtained using a 0.53 mm disk size in 10 MUL PCR
      volume for both STR systems. These protocols proved effective in generating high
      quality profiles on the 3730 DNA Analyzer from both blood and buccal FTA samples.
      Reproducibility, concordance, robustness, sample stability and profile quality
      were assessed using a collection of blood and buccal samples on FTA cards from
      volunteer donors as well as from convicted offenders. The new developed protocols
      offer enhanced throughput capability and cost effectiveness without compromising
      the robustness and quality of the STR profiles obtained. These results support
      the use of these protocols for processing convicted offender samples submitted to
      the National DNA Data Bank of Canada. Similar protocols could be applied to the
      processing of casework reference samples or in paternity or family relationship
      testing.

PMID- 22405518
TI  - Poractant alfa (Curosurf(r)) increases phagocytosis of apoptotic neutrophils by
      alveolar macrophages in vivo.
AB  - BACKGROUND: Clearance of apoptotic neutrophils in the lung is an essential
      process to limit inflammation, since they could become a pro-inflammatory
      stimulus themselves. The clearance is partially mediated by alveolar macrophages,
      which phagocytose these apoptotic cells. The phagocytosis of apoptotic immune
      cells by monocytes in vitro has been shown to be augmented by several
      constituents of pulmonary surfactant, e.g. phospholipids and hydrophobic
      surfactant proteins. In this study, we assessed the influence of exogenous
      poractant alfa (Curosurf(r)) instillation on the in vivo phagocytosis of
      apoptotic neutrophils by alveolar macrophages. METHODS: Poractant alfa (200
      mg/kg) was instilled intratracheally in the lungs of three months old adult male
      C57/Black 6 mice, followed by apoptotic neutrophil instillation. Bronchoalveloar
      lavage was performed and alveolar macrophages and neutrophils were counted.
      Phagocytosis of apoptotic neutrophils was quantified by determining the number of
      apoptotic neutrophils per alveolar macrophages. RESULTS: Exogenous surfactant
      increased the number of alveolar macrophages engulfing apoptotic neutrophils 2.6
      fold. The phagocytosis of apoptotic neutrophils was increased in the presence of
      exogenous surfactant by a 4.7 fold increase in phagocytosed apoptotic neutrophils
      per alveolar macrophage. CONCLUSIONS: We conclude that the anti-inflammatory
      properties of surfactant therapy may be mediated in part by increased numbers of
      alveolar macrophages and increased phagocytosis of apoptotic neutrophils by
      alveolar macrophages.

PMID- 22405519
TI  - Regulation of stress granules in virus systems.
AB  - Virus infection initiates a number of cellular stress responses that modulate
      gene regulation and compartmentalization of RNA. Viruses must control host gene
      expression and the localization of viral RNAs to be successful parasites. RNA
      granules such as stress granules and processing bodies (PBs) contain
      translationally silenced messenger ribonucleoproteins (mRNPs) and serve as
      extensions of translation regulation in cells, storing transiently repressed
      mRNAs. New reports show a growing number of virus families modulate RNA granule
      function to maximize replication efficiency. This review summarizes recent
      advances in understanding the relationship between viruses and mRNA stress
      granules in animal cells and will discuss important questions that remain in this
      emerging field.

PMID- 22405520
TI  - Low serum magnesium concentrations are associated with a high prevalence of
      premature ventricular complexes in obese adults with type 2 diabetes.
AB  - BACKGROUND: Premature ventricular complexes (PVC) predict cardiovascular
      mortality among several adult populations. Increased arrhythmia prevalence has
      been reported during controlled magnesium (Mg) depletion studies in adults. We
      thus hypothesized that serum magnesium (sMg) concentrations are inversely
      associated with the prevalence of PVC in adults at high cardiovascular risk.
      METHODS: Anthropometric, demographic and lifestyle characteristics were assessed
      in 750 Cree adults, aged > 18 yrs, who participated in an age-stratified, cross
      sectional health survey in Quebec, Canada. Holter electrocardiograms recorded
      heart rate variability and cardiac arrhythmias for two consecutive hours.
      Multivariate logistic regression was used to evaluate the associations between
      sMg and PVC. RESULTS: PVC prevalence in adults with hypomagnesemia (sMg <= 0.70
      mmol/L) was more than twice that of adults without hypomagnesemia (50% vs. 21%, p
      = 0.015); results were similar when adults with cardiovascular disease history
      were excluded. All hypomagnesemic adults with PVC had type 2 diabetes (T2DM).
      Prevalence of PVC declined across the sMg concentration gradient in adults with
      T2DM only (p < 0.001 for linear trend). In multivariate logistic regressions
      adjusted for age, sex, community, body mass index, smoking, physical activity,
      alcohol consumption, kidney disease, antihypertensive and cholesterol lowering
      drug use, and blood docosahexaenoic acid concentrations, the odds ratio of PVC
      among T2DM subjects with sMg > 0.70 mmol/L was 0.24 (95% CI: 0.06-0.98) p = 0.046
      compared to those with sMg <= 0.70 mmol/L. CONCLUSIONS: sMg concentrations were
      inversely associated with the prevalence of PVC in patients with T2DM in a dose
      response manner, indicating that suboptimal sMg may be a contributor to
      arrhythmias among patients with T2DM.

PMID- 22405521
TI  - Malignant epignathus including a nephroblastoma component and successful
      management.
AB  - A male infant was born to a 24-year-old mother (gravida 1 para 1) by cesarean
      delivery at 33 1/7 weeks of gestation. The physical examination revealed a large
      mass protruding from the baby's mouth, which appeared to be attached to the
      palate. Tracheostomy was performed immediately in the delivery room. A partial
      surgical excision was performed on the second postnatal day, removing most of the
      teratoma (epignathus), which was attached to the back of the pharynx and
      protruding from the baby's mouth measuring 13*11*9 cm and weighing 545 g. The
      final pathological diagnosis was "malignant epignathus with nephroblastoma
      component." According to our knowledge, this is the first case that have
      malignant epignathus including nephroblastoma component in the literature.

PMID- 22405523
TI  - Designing group sequential randomized clinical trials with time to event end
      points using a R function.
AB  - A major and difficult task is the design of clinical trials with a time to event
      endpoint. In fact, it is necessary to compute the number of events and in a
      second step the required number of patients. Several commercial software packages
      are available for computing sample size in clinical trials with sequential
      designs and time to event endpoints, but there are a few R functions implemented.
      The purpose of this paper is to describe features and use of the R function.
      plansurvct.func, which is an add-on function to the package gsDesign which
      permits in one run of the program to calculate the number of events, and required
      sample size but also boundaries and corresponding p-values for a group sequential
      design. The use of the function plansurvct.func is illustrated by several
      examples and validated using East software.

PMID- 22405522
TI  - Mucin-secreting clear cell renal cell carcinoma. A rare variant of conventional
      renal cell carcinoma.
AB  - We report herein one case of conventional renal cell carcinoma (RCC) producing
      extensive extracellular mucinous secretion in a 71-year-old man. To the best of
      our knowledge, the presence of mucinous secretion in this tumor has not been
      documented. Mucin production, despite its low frequency, can be considered an
      additional feature of conventional RCC. Therefore, clear cell RCC should be added
      to the list of parenchymal renal tumors that can show significant mucin
      secretion; and it should be included in the inventory of morphologic variations
      of this tumor, which may cause diagnostic difficulties. It is of primary
      importance to distinguish mucin-secreting clear cell RCC from the metastasis of a
      mucin-secreting tumor to conventional RCC. Presence of mucin in a clear cell
      carcinoma does not exclude a renal origin.

PMID- 22405524
TI  - Efficient inhomogeneity compensation using fuzzy c-means clustering models.
AB  - Intensity inhomogeneity or intensity non-uniformity (INU) is an undesired
      phenomenon that represents the main obstacle for magnetic resonance (MR) image
      segmentation and registration methods. Various techniques have been proposed to
      eliminate or compensate the INU, most of which are embedded into classification
      or clustering algorithms, they generally have difficulties when INU reaches high
      amplitudes and usually suffer from high computational load. This study
      reformulates the design of c-means clustering based INU compensation techniques
      by identifying and separating those globally working computationally costly
      operations that can be applied to gray intensity levels instead of individual
      pixels. The theoretical assumptions are demonstrated using the fuzzy c-means
      algorithm, but the proposed modification is compatible with a various range of c
      means clustering based INU compensation and MR image segmentation algorithms.
      Experiments carried out using synthetic phantoms and real MR images indicate that
      the proposed approach produces practically the same segmentation accuracy as the
      conventional formulation, but 20-30 times faster.

PMID- 22405525
TI  - Serum biochemical indicators of hepatobiliary function in dogs following
      prolonged anaesthesia with sevoflurane or isoflurane.
AB  - OBJECTIVE: To investigate the changes in serum enzymes considered as biochemical
      indicators of hepatobiliary function in dogs following 5 hours of anaesthesia
      with isoflurane (ISO) or sevoflurane (SEVO). STUDY DESIGN: Experimental
      randomized crossover study, with intervals of at least 15 days between successive
      treatments. ANIMALS: Eight healthy adult mongrel dogs, four male, four female,
      weight 13.6-21.6 kg. METHODS: Treatments consisted of anaesthesia with ISO or
      SEVO at 1 or 1.5 minimum alveolar concentration (MAC) delivered in oxygen. MAC
      was taken as 1.39% for ISO and 2.36% for SEVO. Anaesthesia was induced by mask
      then, after endotracheal intubation, maintained according to the treatment
      protocol using a small animal circle system. Cardiopulmonary monitoring was
      carried out. Venous blood samples, obtained by needle puncture, were taken at 24
      hours and 2, 7 and 14 days post anaesthesia. Serum concentrations of total
      protein, aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      lactate dehydrogenase, (LDH), alkaline phosphatase (ALP), gamma
      glutamyltransferese and total bilirubin were measured. Changes with time and with
      treatment were compared by Friedman analysis, Wilcoxon Signed test and Kruskal
      Wallis test as relevant. p- value < 0.05 was considered significant. RESULTS:
      Compared to base-line values, at 24 hours post-anaesthesia there were significant
      increases in AST, ALT, ALP and LDH following one or more of the treatments, but
      by 2 days residual changes were not significant. At 24 hours, AST for treatment
      1.5 MAC ISO was higher than 1 MAC ISO (p < 0.002), and LDH higher for 1.5 MAC
      SEVO than 1 MAC SEVO. CONCLUSION AND CLINICAL RELEVANCE: Both ISO and SEVO, at
      concentrations used for clinical anaesthesia, produce transient moderate effects
      on some hepatobiliary enzyme concentrations in dogs.

PMID- 22405526
TI  - Safety and efficiency of multiple square sutures to avoid peripartum
      hysterectomy.

PMID- 22405529
TI  - K-band single-chip electron spin resonance detector.
AB  - We report on the design, fabrication, and characterization of an integrated
      detector for electron spin resonance spectroscopy operating at 27 GHz. The
      microsystem, consisting of an LC-oscillator and a frequency division module, is
      integrated onto a single silicon chip using a conventional complementary metal
      oxide-semiconductor technology. The achieved room temperature spin sensitivity is
      about 10(8)spins/G Hz(1/2), with a sensitive volume of about (100 MUm)(3).
      Operation at 77K is also demonstrated.

PMID- 22405527
TI  - Toxic environmental chemicals: the role of reproductive health professionals in
      preventing harmful exposures.
AB  - Every pregnant woman in the United States is exposed to many and varied
      environmental chemicals. Rapidly accumulating scientific evidence documents that
      widespread exposure to environmental chemicals at levels that are encountered in
      daily life can impact reproductive and developmental health adversely.
      Preconception and prenatal exposure to environmental chemicals are of particular
      importance because they may have a profound and lasting impact on health across
      the life course. Thus, prevention of developmental exposures to environmental
      chemicals would benefit greatly from the active participation of reproductive
      health professionals in clinical and policy arenas.

PMID- 22405530
TI  - A population-based study of factors affecting the use of radiotherapy for
      endometrial cancer.
AB  - AIMS: To describe the use of adjuvant radiotherapy for endometrial cancer in
      Ontario, and identify factors associated with its use, and to determine whether
      variation in the use of radiation is associated with differences in survival.
      MATERIALS AND METHODS: This was a retrospective, population-based, cohort study
      of all patients who had a hysterectomy for endometrial cancer in Ontario between
      1992 and 2003. We used multiple logistic regression to identify health system
      related factors associated with the use of radiotherapy, while controlling for
      disease- and patient-related factors. Survival and cancer cause-specific survival
      were compared among regions of the province with higher and lower rates of use of
      radiotherapy. RESULTS: The study population included a total of 9411 women with a
      median age of 63 years. Overall, 26.2% received adjuvant radiotherapy. Patients
      living further from regional cancer centres were slightly less likely to receive
      radiation (P = 0.02). Patients who had their surgery during longer prevailing
      waiting times for radiotherapy were less likely to receive radiation (P = 0.04).
      The use of radiotherapy varied widely from 18.0 to 34.3% among the catchment
      areas of provincial radiotherapy centres (P < 0.0001). In the overall population,
      there was no difference in survival among regions with higher and lower rates of
      use of radiotherapy. However, in the subgroup of cases with clear cell and serous
      carcinomas, both overall survival and cancer cause-specific survival were
      significantly lower in regions with lower rates of use of radiotherapy (P <
      0.05). This difference remained significant after controlling for other factors
      (P < 0.05; hazard ratio 1.43; 95% confidence limits 1.06-1.93). CONCLUSIONS:
      Health system-related factors unrelated to patients' needs affect the use of
      adjuvant radiotherapy in Ontario. Lower rates of use of adjuvant radiotherapy are
      associated with lower rates of survival in patients with serous and clear cell
      carcinomas.

PMID- 22405531
TI  - Closure of the alveolar cleft by bone segment transport using an intraoral tooth
      borne custom-made distraction device.
AB  - PURPOSE: The fact that bone transportation generates not only bone but also
      surrounding soft tissues makes it an ideal technique for tissue regeneration.
      This study evaluates bone segment transport using an intraoral tooth-borne
      distraction device for alveolar cleft closure. MATERIALS AND METHODS: Patients
      with an alveolar cleft were enrolled in the study. They were treated at the Al
      Azhar University Hospital, Cairo, Egypt, between 2004 and 2007. Anterior
      transportation of the posterior dentoalveolar segment was performed by use of an
      intraoral tooth-borne custom-made distractor. Clinical evaluations included the
      following: preoperative and postoperative intraoral photographs, vitality testing
      of the teeth in the transport segment, cast analysis, and measurement of tooth
      mobility. Radiographic evaluations included occlusal films, orthopantomography,
      and computed tomography and 3D computed tomography for volumetric and
      densitometric evaluations of the distracted bone. RESULTS: After distraction was
      completed, the transported segments were positioned 1 to 4 mm superior to the
      occlusal plane. The radiographic evaluation showed residual triangular bone
      deficits that were closed through gingivoperiosteoplasty or bone grafting. Once
      the transported segments came in contact with the alveolar bone of the normal
      side, the intervening fibrous tissue at the docking site was removed, and docking
      site surgery was then performed. The results obtained from both clinical
      examinations and radiographic imaging showed complete closure of the alveolar
      clefts. CONCLUSIONS: Maxillary alveolar bone transport offers an alternative
      technique in the latest treatment of the alveolar cleft.

PMID- 22405532
TI  - Dental implant distractor combined with free fibular flap: a new design for
      simultaneous functional mandibular reconstruction.
AB  - PURPOSE: The purpose of the present study was to present a new method that
      combines the use of the fibular flap and a custom-made vertical distractor/dental
      implant device into 1 surgical procedure for simultaneous functional mandibular
      reconstruction. PATIENTS AND METHODS: The present retrospective case series
      included 10 patients who were treated using the fibular flap and dental implant
      distractor (DID) in a single-stage procedure. These 10 patients were treated
      within a 3-year period (from 2005 to 2007). RESULTS: Of the 10 patients included
      in the study, 5 were males and 5 were females. The mean age of the sample was
      33.8 years (range 17 to 48). The cumulative survival rate of the fibular flaps
      was 100%. The mean vertical bone height attained with the DID device was 11.4 mm.
      The mean period from the first operation to the start of dental implant loading
      was 6.3 months. The cumulative survival rate of the dental implants was 93.75%.
      CONCLUSIONS: The use of the DID in the fibular flap for mandibular reconstruction
      is advantageous because it combines vertical distraction osteogenesis of the
      fibular flap and dental implantation into a single procedure. Implants placed in
      the reconstructed areas were found to integrate normally, with survival rates
      comparable to those with 2-stage operations. As such, this novel DID technique
      can be used for single-stage reconstruction and rehabilitation of segmental
      mandibular defects in selected patients.

PMID- 22405533
TI  - Etiology analysis and computed tomography imaging of a tonsillar inflammatory
      myofibroblastic tumor: report of an immunocompetent patient and brief review.
AB  - OBJECTIVES: The etiology of Inflammatory myofibroblastic tumor(IMT) is
      contentious. In this study, we used computed tomography (CT) to examine tonsillar
      IMT and further analyzed the etiology of this entity. METHODOLOGY: We presented
      CT features of left tonsillar IMT and reviewed the English-language literature
      published between 1984 and 2011. RESULTS: To our knowledge, there are only six
      published cases of tonsillar IMT including the present case. Two patients were
      asymptomatic at initial presentation. Two patients were taking
      immunosuppressants, and one was pregnant and in an immunomodulated state. CT of
      our patient revealed a 2.6 * 1.8 cm irregular soft tissue mass between the left
      tonsil and the base of the tongue. It did not invade surrounding structures and
      was not enhanced on contrast-enhanced imaging. CONCLUSIONS: Tonsillar IMT may be
      a benign tumor. We suggest that preoperative recognition of tonsillar IMT by CT
      may be important to avoid unnecessary expanded surgery.

PMID- 22405534
TI  - Cold plasma is well-tolerated and does not disturb skin barrier or reduce skin
      moisture.
AB  - BACKGROUND: Cold plasma, a new treatment principle in dermatology based on ionic
      discharge delivering reactive molecular species and UV-light, exhibits strong
      antimicrobial efficacy in vitro and in vivo. Before implementing plasma as new
      medical treatment tool, its safety must be proven, as well as assessing skin
      tolerance and patient acceptance. PATIENTS AND METHODS: We investigated the
      plasma effects of three different plasma sources (pulsed, non-pulsed atmospheric
      pressure plasma jet (APPJ) and a dielectric barrier discharge (DBD)) on the
      transepidermal water loss (TEWL) and skin moisture after treating the fingertips
      of four healthy male volunteers. RESULTS: TEWL values were reduced by pulsed APPJ
      and DBD by about 20% but increased after non-pulsed APPJ by 5-20%. TEWL values
      normalized 30 min after all forms of plasma treatment. Skin moisture was
      increased immediately and 30 min after treatment with pulsed APPJ but was not
      affected by non-pulsed APPJ and DBD. CONCLUSIONS: All plasma treatments were well
      tolerated and did not damage the skin barrier nor cause skin dryness. Cold plasma
      fulfils basic recommendations for safe use on human skin and as future option may
      serve as the first physical skin antiseptic.

PMID- 22405535
TI  - Does a diet high or low in fat influence the oxidation potential of VLDL, LDL and
      HDL subfractions?
AB  - BACKGROUND AND AIMS: High-fat diets have become increasingly popular for weight
      loss, but their effect on the oxidation potential of lipoprotein subfractions has
      not been studied. Therefore, this study compared the effects of high-fat vs. low
      fat weight reduction diets on this parameter. METHODS AND RESULTS: Very-low, low-
      and high-density lipoprotein (VLDL, LDL & HDL) subfractions were isolated by
      rapid ultracentrifugation from 24-overweight/obese subjects randomised to a high-
      or low-fat diet. The lipoprotein subfractions were assessed for oxidation
      potential by measuring conjugated diene (CD) production and time at half maximum.
      We found a significant between-group difference in oxidation potential.
      Specifically, a high-fat diet led to increased CD production in VLDL(A-D) and
      HDL(2&3), and a prolongation of time at half maximum. Within-group differences
      found that CDs increased in VLDL(A&D), LDL(I-III) and HDL(2&3) in the high-fat
      group and fell in VLDL(A-C) and HDL(2&3) and increased in LDL(I&II), in the low
      fat group. Furthermore, following both diets all lipoprotein subfractions, except
      LDL(II) in the low-fat group, were protected against oxidation. CONCLUSION: These
      results demonstrate that at first glance, a high-fat diet may be indicative of
      having heart-protective properties. However, this may be erroneous, as although
      the time for oxidation to occur was prolonged, once this occurred these
      lipoproteins had the potential to produce significantly more oxidised substrate.
      Conversely, a low-fat diet may be considered anti-atherogenic, as these
      subfractions were protected against oxidation and mainly contained fewer oxidised
      substrate. Thus, increased fat intake may, by increasing the oxidation product
      within lipoprotein subfractions, increase cardiovascular disease.

PMID- 22405536
TI  - A simple method for the determination of peak distribution in comprehensive two
      dimensional liquid chromatography.
AB  - In LC * LC the peak capacity (2D)n and the orthogonality O are often used as
      parameters of resolving power. Unfortunately, these parameters are not easily
      accessible from chromatograms. In this work we will present a novel method, based
      on the description as vectors of experimentally easily accessible data. This
      approach makes it possible to calculate separation space (peak distribution) in
      parallelograms and other more complex geometric patterns by describing a two
      dimensional area by vectors. The calculated separation space allows a comparison
      between several column combinations and is a useful tool in optimization of LC *
      LC analysis.

PMID- 22405537
TI  - Multi-wavelength high-performance liquid chromatographic fingerprints and
      chemometrics to predict the antioxidant activity of Turnera diffusa as part of
      its quality control.
AB  - The determination of the antioxidant activity of Turnera diffusa using partial
      least squares regression (PLSR) on chromatographic data is presented. The
      chromatograms were recorded with a diode array detector and, for each sample, an
      enhanced fingerprint was constructed by compiling into a single data vector the
      chromatograms at four wavelengths (216, 238, 254 and 345 nm). The wavelengths
      were selected from a contour plot, in order to obtain the greater number of peaks
      at each of the wavelengths. A further pretreatment of the data that included
      baseline correction, scaling and correlation optimized warping was performed.
      Optimal values of the parameters used in the warping were found by means of
      simplex optimization. A PLSR model with four latent variables (LV) explained
      52.5% of X variance and 98.4% of Y, with a root mean square error for cross
      validation of 6.02. To evaluate its reliability, it was applied to an external
      prediction set, retrieving a relative standard error for prediction of 7.8%. The
      study of the most important variables for the regression indicated the
      chromatographic peaks related to antioxidant activity at the used wavelengths.

PMID- 22405538
TI  - Packed column supercritical fluid chromatography of hydrophilic analytes via
      water-rich modifiers.
AB  - The use of additives to dramatically extend the range of solute polarity amenable
      to CO(2) based supercritical fluid chromatography (pcSFC) was predicted over 20
      years ago. At that time additives were predicted to have multiple functions such
      as enhancement of mobile phase solvating power, ion suppression, and ion pairing.
      The adsorption of mobile phase components on the stationary phase causing a
      modification of its surface was predicted, but the implications for separations
      were not defined. Reports published in the late 1980s showed that while water
      could not function as a primary modifier due to it poor solubility in carbon
      dioxide, its use as an additive was more promising. The past decade has seen very
      little published work concerning water and pcSFC. Now reports are beginning to
      appear that demonstrate enhanced selectivity with water, and application of the
      technology to polypeptide salts, drug molecules, and nucleobases. This review
      attempts to bridge the past with the present. As evidenced by the studies
      described in this review, water may offer much potential as an additive in that
      it could (a) enhance the solvating power of the mobile phase, (b) introduce HILIC
      like analyte partitioning, (c) simplify preparative purifications, and (d) offer
      a more mass spectrometrically compatible interface.

PMID- 22405539
TI  - Determination of descriptors for fragrance compounds by gas chromatography and
      liquid-liquid partition.
AB  - Retention factors on a minimum of eight stationary phases at various temperatures
      by gas-liquid chromatography and liquid-liquid partition coefficients for five
      totally organic biphasic systems were combined to estimate descriptors for 28
      fragrance compounds with an emphasis on compounds that are known or potential
      allergens. The descriptors facilitated the estimation of several properties of
      biological and environmental interest (sensory irritation threshold, odor
      detection threshold, nasal pungency threshold, skin permeability from water, skin
      water partition coefficients, octanol-water partition coefficients, absorption by
      air particles, adsorption by diesel soot particles, air-water partition
      coefficients, and adsorption by film water). The descriptors are suitable for use
      in the solvation parameter model and facilitate the estimation of a wide range of
      physicochemical, chromatographic, biological, and environmental properties using
      existing models.

PMID- 22405540
TI  - Review of the dielectric properties of nanofiltration membranes and verification
      of the single oriented layer approximation.
AB  - The structuring of water at soft solid surfaces remains an area of great interest
      to colloid science as a whole and has many applications in relation to colloid
      stability, foams, and wetting films as well as being central to membrane
      separations. Quantitatively calculating the structural components of thin layers
      of water and the interaction forces of hydrated molecules with the surface of
      pores through a layer of water having modified structure is one of the most
      important challenges in the physics of surface phenomenon. In this paper these
      effects are reviewed and discussed in relation to the confines of a capillary
      pore. Membrane nanofiltration is extremely complex and is dependent on the micro
      hydrodynamics and interfacial events occurring at the membrane surface and within
      the membrane nanopores. There is significant debate as to the exact nature of
      these complex phenomena and rejection is typically attributed to a combination of
      steric and electrical effects. The electrical effects are less well understood
      and in particular the contribution of dielectric exclusion. A review of the two
      competing descriptions of dielectric exclusion is presented along with the
      theories currently used in modelling this phenomena. A series of rejection
      experiments of 0.01 M salt solutions at the membrane isoelectric point has been
      performed for the NF270 and NF99HF membranes. The dielectric constants inside the
      nanopore are calculated and these values were consistent for three of the salts
      studied, indicating that a simplistic model based on Born theory is accurate
      enough for engineering calculations and that ion solvation is most likely to be
      the more appropriate dielectric exclusion mechanism for true nanofiltration
      membranes.

PMID- 22405541
TI  - Suspension flow in microfluidic devices--a review of experimental techniques
      focussing on concentration and velocity gradients.
AB  - Microfluidic devices are an emerging technology for processing suspensions in
      e.g. medical applications, pharmaceutics and food. Compared to larger scales,
      particles will be more influenced by migration in microfluidic devices, and this
      may even be used to facilitate segregation and separation. In order to get most
      out of these completely new technologies, methods to experimentally measure (or
      compute) particle migration are needed to gain sufficient insights for rational
      design. However, the currently available methods only allow limited access to
      particle behaviour. In this review we compare experimental methods to investigate
      migration phenomena that can occur in microfluidic systems when operated with
      natural suspensions, having typical particle diameters of 0.1 to 10 MUm. The
      methods are used to monitor concentration and velocity profiles of bidisperse and
      polydisperse suspensions, which are notoriously difficult to measure due to the
      small dimensions of channels and particles. Various methods have been proposed in
      literature: tomography, ultrasound, and optical analysis, and here we review and
      evaluate them on general dimensionless numbers related to process conditions and
      channel dimensions. Besides, eleven practical criteria chosen such that they can
      also be used for various applications, are used to evaluate the performance of
      the methods. We found that NMR and CSLM, although expensive, are the most
      promising techniques to investigate flowing suspensions in microfluidic devices,
      where one may be preferred over the other depending on the size, concentration
      and nature of the suspension, the dimensions of the channel, and the information
      that has to be obtained. The paper concludes with an outlook on future
      developments of measurement techniques.

PMID- 22405542
TI  - A colloid cyst in the fourth ventricle complicated with aseptic meningitis: a
      case report.

PMID- 22405543
TI  - Neurodevelopmental outcome of 31 patients with borderline fetal ventriculomegaly.
AB  - AIM: We present the neurodevelopmental outcome of patients with isolated
      borderline fetal ventriculomegaly. METHODS: The present study was carried out at
      the Department of Pediatric Neurology, Istanbul Medical Faculty, Istanbul
      University in July-December 2010. Prenatal second trimester detailed ultrasound
      examinations were performed by obstetricians at the Prenatal Diagnosis Department
      of Istanbul Medical School, and 31 consecutive patients aged 8-33 months have
      been included in the study. Four patients with atrial diameters of over 15 mm and
      three patients with central nervous system development anomalies were excluded
      from the study. In order to assess the neuromotor development of patients,
      neurologic examinations and the Bayley Scales of Infant Development (BSID-III)
      were used. RESULTS: Nine patients were female (29%) and 22 were male (71%). In
      the postnatal period, tuberous sclerosis was found in one patient, Down syndrome
      in one, and equinovarus foot deformity in one. Atrial diameter was <12 mm in 18
      patients and >12 mm in 13. Cranial ultrasounds done in the first postnatal month
      revealed persisting ventriculomegaly in nine patients. The two patients who
      scored significantly low in all areas on the Bayley Scales of Infant Development
      were the patients with Down syndrome and tuberous sclerosis. The one scoring low
      in the motor area was the patient with the equinovarus foot deformity. The BSID
      III scores of the patients whose prenatal ventricle diameter was <12 mm were
      within normal limits. The four patients showing slight developmental delay were
      the ones whose cranial ultrasound in the first postnatal month showed persisting
      ventriculomegaly. CONCLUSION: In patients with borderline fetal ventriculomegaly,
      atrial diameter being more than 12 mm, the condition persisting in the first
      postnatal month and the presence of accompanying syndromes and malformations all
      constitute clear risk factors for neurodevelopmental outcome.

PMID- 22405544
TI  - Current concepts in fractures of the distal femur.
AB  - This paper describes current treatment strategies of distal femoral fractures as
      well as their evidence based rationale. The treatment of distal femoral fractures
      has improved with the evolution of plating and nailing technologies. The commonly
      selected surgical approaches are outlined and surgical treatment techniques
      including both internal and external fixation are discussed.

PMID- 22405545
TI  - Tarsometatarsal joint complex and midtarsal injuries.
AB  - In this article the following areas will be reviewed; the anatomy of the midfoot;
      mechanisms of injury and current classification systems; diagnosis; treatment
      options and the evidence for current practice; areas of treatment uncertainty and
      recommended guidelines for management.

PMID- 22405546
TI  - [Surgical treatment for atlantoaxial osteoarthritis (AAOA): a prospective study
      of twenty-seven patients].
AB  - PURPOSE OF THE STUDY: Atlantoaxial osteoarthritis (AAOA) is a clinical syndrome
      with signs distinctly different from those of degenerative sub - axial spine
      disease. Its diagnosis may long be delayed, partly because of insufficient
      knowledge and partly due to difficulties in interpreting both anteroposterior and
      lateral radiographs. The aim of this prospective study was to evaluate the first
      27 AAOA patients treated at our department. MATERIAL: From 2001 we performed
      atlantoaxial fixation with fusion in a total of 29 patients with painful
      arthritis of the atlanto axial complex. The 27 patients treated before the end of
      2010 were enrolled in the study and analysed in detail. This group included 13
      women and 14 men aged between 35 and 72 years, with an average age of 53.5 years.
      In all patients atlanto - axial fixation was performed using the polyaxial screw
      rod system according to Harms. METHODS: The patients were followed up at 6 and 12
      weeks, 6 and 12 months and then once a year after surgery. X-ray examinations
      were done at the same intervals as clinical examinations; functional radiographs
      were made at 12 to 14 weeks after surgery. The definitive analysis of the group
      was made in the range of 4 to 59 months (average, 25.7 months) after the primary
      operation. Patients' subjective evaluation was based on NPDI and VAS scores and a
      question of whether the patient would undergo the surgery again. Objective
      evaluation included clinical outcomes - pain and neurological findings;
      radiographic results - stability and healing of C1-C2 fusion; and complications
      during surgery and in early and late postoperative periods. As intra-operative
      complications were regarded those associated with the surgical approach, nerve
      injury and vertebral artery injury. Early post-operative complications included
      poor wound healing and changes in the patient's neurological status, late
      complications included instrumentation failure and infection. Patients' clinical
      status (NPDI, VAS) was statistically evaluated using the one-way ANOVA. RESULTS:
      The mean VAS score was pre-operatively 7.0 and post-operatively 5.6 at 3 months,
      5.0 at 6 months, 5.1 at 1 year; 3.9 at 2 years and 4.0 at 3 years. The mean NPDI
      value was pre-operatively 39.6 and post-operatively 38.7 at 3 months, 36.0 at 6
      months, 34.5 at 1 year, 34.3 at 2 years and 33.1 at 3 years. The question of
      willingness to undergo the same operation again was answered in the affirmative
      by 21 patients (77.8%), in the negative by five (18.5%) and one patient did not
      know (3.7%). Complete bone fusion, as assessed by radiography or CT scanning, was
      achieved in 26 out of 27 patients (96.3%). In one patient the result was
      ambiguous but, at 3 months as well as the next follow-ups, C1-C2 complex
      stability was found. DISCUSSION: All patients in our group underwent a unified
      system of clinical, radiological, CT and MRI examination. In the decision-making
      process, emphasis was placed on a correlation of clinical findings with CT
      scanning results. All patients were operated on from the posterior approach using
      the Harms method, and radiological outcomes were similar to those of Grob et al.
      who used the Magerl's technique of C1-C2 fixation. The VAS and NPDI scores
      demonstrated significant improvement as early as 3 post-operative months, with
      still further improvement in the following period. The stable clinical status of
      the patients was achieved at 2 years after surgery. From the practical standpoint
      we were interested in an answer to the question of whether the patients would be
      willing to undergo the procedure again. Almost 80% of affirmative answers
      testified to the correct choice of treatment. The values found corresponded to
      those reported by Grob at al. CONCLUSIONS: Patients with painful osteoarthritis
      refractory to conservative treatment will benefit from atlantoaxial fixation and
      fusion. For the patient, restricted cervical rotation is acceptable in return for
      pain relief. From the surgical point of view, the risk of complications
      associated with the operative technique did not exceed a tolerable rate.

PMID- 22405547
TI  - [Lumbar total disc replacement. Short-term results].
AB  - PURPOSE OF THE STUDY: Motion-preservation technologies for spinal disorders have
      evolved and come into use in the last decade. Three principal systems are
      currently available: total disc replacement, posterior neutralisation
      transpedicular system and interspinous implants. The aim of this retrospective
      study was to evaluate our group of lumbar total disc replacements at a follow-up
      of 2 years. MATERIAL AND METHODS: A total of 42 disc prostheses were implanted in
      37 patients. Of these, 31 with 35 artificial discs were followed up for 2 years.
      There were 11 men and 20 women with an average age of 42.9 years (range, 21 to 61
      years). The indication for surgery was lumbar disc pain without radicular
      syndrome and contraindications included advanced degenerative facet joint disease
      and obesity with a body mass index over 30. Surgery was carried out through the
      pararectal retroperitoneal approach. Early and late complications were recorded.
      The group evaluation was based on radiological outcomes, and VAS and ODI scores
      reported by the patients at 6 weeks, and 3, 6, 12 and 24 months after surgery.
      RESULTS: The average operative time was 68 minutes (range, 36 to 120 min) for
      single-level lumbar total disc replacement and 92 minutes (range, 72 to 130 min)
      for two-level procedures. The average hospital stay was 5.2 days (range, 3 to
      12). Both keels of the prosthesis were in the exact center in 25 cases, they were
      shifted laterally in nine cases up to 2 mm and in one case more than 2 mm.
      Horizontal rotation of the prosthesis was seen in two patients, but not more than
      5 degrees to the left. There was no disc loosening or subsidence, and no
      acceleration of adjacent segment degeneration. Two patients showed heterotopic
      ossification. Subjective evaluation was recorded as marked improvement in 15,
      partial improvement in 11 and no change in five patients. None of the patients
      reported deterioration. Low back pain assessed by the VAS score had an average
      value of 66.3 before surgery and 14.1 at 2 years after surgery. The average pre
      operative ODI value was 48.9 and that at 2 years post-operatively was 24.5.
      DISCUSSION: Pain relief evaluated by the VAS score in our study is comparable
      with or slightly better than is reported by the other authors. Some recorded
      average values for lumbago were 74 before surgery and 35 at 2 years of follow-up,
      or 62.3 before and 25.4 at 2 years after surgery, while our patients had the
      average VAS score of 66.3 before surgery and that of 18.4 at 2 years after
      surgery. The ODI values in our group were similar to those of other authors. When
      we compare this group with the group of our patients who were treated by spinal
      fusion surgery, the outcomes at 1 year are better in the total disc replacement
      group, as shown by the VAS for lumbago of 17.8 and ODI of 24.5 in the former
      versus the respective values of 18.1 and 29.0 in the latter group. CONCLUSION:
      Based on the results it can be concluded that total disc replacement is an
      efficient method of treating degenerative intervertebral disc disease of the
      lumbar spine in young, active and motivated patients with no posterior spinal
      structure degeneration.

PMID- 22405548
TI  - [Anatomical double-bundle anterior cruciate ligament reconstruction - transtibial
      versus anteromedial reaming of femoral tunnels].
AB  - PURPOSE OF THE STUDY: The aim of the study was to compare two options of how to
      get the correct anatomical position of both femoral tunnels, using the
      transtibial or the anteromedial portal technique, during anatomical double-bundle
      anterior cruciate ligament (ACL) reconstruction. MATERIAL AND METHODS: A total of
      36 patients, 29 men and seven women, underwent double-bundle ACL reconstruction
      between October 2009 and December 2010. Their average age was 26.5 years. The
      average interval between ACL injury and reconstruction was 7.4 months. A
      diagnostic arthroscopy for the treatment of cartilage and meniscal lesions was
      performed in 21 patients and one-stage ACL reconstruction with diagnostic
      arthroscopy was carried out in the remaining 15 patients. In all 36 patients, the
      position of the tip of the guide wire in relation to the anatomical insertion
      sites of both the anteromedial (AM) and posterolateral (PL) bundles was assessed
      intra-operatively. Three guide wire positions were found: the tip was in the
      centre of the native insertion site, the tip was within the insertion site but
      not in its centre, and the tip was outside the insertion site. RESULTS: Using the
      transtibial technique through the AM tunnels, the tip of the guide wire was
      centred within the femoral AM insertion site only in one patient (2.8%), out of
      the centre but within the AM insertion site in four patients (11.1%) and outside
      the insertion site in the remaining 31 patients (86.1%). With this technique, the
      position of the femoral PL tunnels was outside the native PL insertion site in
      all 36 patients. With the transtibial technique using the PL tunnels, the tip of
      the guide wire was centred within the femoral AM native insertion in 11 patients
      (30.5%), out of the centre but still within the AM insertion site in 16 (44.5%)
      and outside the AM insertion site in nine patients (25%). Aiming for the femoral
      PL tunnel resulted in the tip of the guide wire being outside the native femoral
      PL insertion site in all cases. Using the technique of guide wire insertion
      through an accessory AM portal it was possible to achieve the centres of both the
      AM and PL native anatomical insertion sites in all 36 patients (100%).
      DISCUSSION: We agree with the many authors who recommend the reaming of PL
      femoral tunnels through an accessory AM portal because the transtibial technique
      does not allow for the placement of their precise native anatomical positions.
      Our intraoperative findings showed that the transtibial technique was effective
      to get the correct anatomical position of AM femoral tunnels just in 30.5% of the
      patients. In view of the fact that the same results can be achieved with the AM
      transportal technique in 100% of the patients, we prefer this technique in
      accordance with the majority of other authors. CONCLUSIONS: In anatomical double
      bundle ACL reconstruction, the native anatomical position of PL tunnels was
      achieved in all patients and the native AM tunnels in most of them using the
      accessory AM portal technique. The transtibial technique proved to be
      unsatisfactory.

PMID- 22405549
TI  - [Treatment of sequelae after Monteggia lesions in childhood].
AB  - PURPOSE OF THE STUDY: To review the current methods of operative management of
      post-traumatic chronic radial head dislocation in chronic Monteggia lesions in
      children. MATERIAL AND METHODS: Post-traumatic chronic dislocation of the
      proximal radius usually occurs following missed or ineffectively treated
      Monteggia fractures. The radial head is usually dislocated anteriorly. We
      performed open reduction of the radial head, reconstruction of the annular
      ligament and corrective osteotomy of the ulna in eleven patients. Three of our
      patients underwent ulnar lengthening via gradual distraction using an Ilizarov
      external fixator. This procedure was used in nine boys and five girls who were
      treated for complications following Monteggia lesions between 2000 and 2009. The
      average age at the time of surgery was 8 years and 4 months, the average injury
      to-surgery interval was 19 months, and a prerequisite for surgery was a normal
      concave articular surface of the proximal radius. The patients were followed up
      for an average of 28 months and, at final follow-up, all were fully active and
      had no pain or instability. RESULTS: The complications included: non-union of the
      ulnar osteotomy site in two patients, residual radiocapitellar subluxation in two
      patients, and one patient had revision surgery. Nine patients showed a full range
      of motion, two had a loss of extension, and three had a mean loss of pronation of
      20 degrees and a mean loss of supination of 20 degrees. DISCUSSION: The Monteggia
      lesion is a rare fracture in childhood, but its sequelae can be serious. So far a
      unified therapeutic approach has not been proposed. Most authors prefer
      reconstruction surgery. Our results are in full agreement with the published
      data. CONCLUSIONS: The operative treatment of consequences after Monteggia
      fractures in children has a relatively high rate of complications and
      unpredictable results. Indications for reconstruction involve a normal articular
      surface of the radial head and a normal alignment of the radius and ulna. Key
      words: Monteggia fracture, consequences, reconstruction surgery, childhood.

PMID- 22405550
TI  - [Bone healing capacity in patients undergoing total hip arthroplasty].
AB  - PURPOSE OF THE STUDY: To identify some characteristics of bone repair capacity in
      elderly patients who undergo total hip arthroplasty, which requires good healing
      ability of bone for implant osteointegration and bone defect repair, particularly
      if revision arthroplasty is necessary. MATERIAL AND METHODS: In a group of 27
      patients (mean age, 70 +/- 7 years; range, 60 to 81 years) a coincidence of
      osteoarthritis and osteopenia/ osteoporosis was assessed, and mesenchymal stem
      cells (MSC) were isolated and their numbers, viability and proliferative capacity
      were evaluated. The MSC populations were examined for their behaviour on bone
      tissue scaffolds used in orthopaedic surgery for treatment of bone lesions. Each
      patient underwent bone densitometry examination before total hip arthroplasty.
      Bone marrow was harvested intra-operatively from the trochanteric region of the
      femur. From a portion of bone marrow, MSCs were isolated and cultured, and a
      mononuclear cell concentrate was obtained. Either whole bone marrow or a
      mononuclear cell concentrate was applied to selected matrices (allograft,
      demineralised bone matrix, porous beta-tricalcium phosphate (-TCP), pressed
      hydroxyapatite or calcium sulphate). The production of new collagen and
      extracellular mineralized matrix were first assessed in expansion medium and,
      when the production was low, differentiation medium was used. RESULTS: A
      coincidence of osteoarthritis and osteopenia/osteoporosis was found in 50% of the
      patients. All were women with a low body mass index and had been post-menopausal
      for an average of 23 years. The isolated MSCs contained a high percentage of
      viable cells (mean, 95%). The mesenchymal cells of patients with osteopenia, as
      compared with those having normal bone density, showed markedly lower numbers of
      fibroblastic colony forming units (CFU-F) per ml and had a lower proliferative
      capacity because the population doubling time during the first four passages was
      much longer. Of the scaffolds tested, allografts showed the most marked collagen
      and extracellular mineralized matrix production in expansion medium with either
      whole bone marrow or a monocyte concentrate; porous -TCP was the best of bone
      graft substitutes in collagen and extracellular mineralized matrix production by
      both whole bone marrow and a monocyte concentrate, but this was only in
      differential medium. DISCUSSION: The coincidence of ostearthritis with
      osteopenia/osteoporosis was found in a higher number of our patients than is
      reported in the literature. Also, a lower MSC proliferative capacity and a low
      number of CFU-F/ml in the patients with low bone density were interesting
      findings. Better bone regeneration would generally be achieved with higher MSC
      numbers and the use of growth factors for stimulation of osteoinduction and
      angiogenesis. Bone marrow harvesting for MSC isolation, cultivation and
      subsequent transplantation is currently feasible only in an experiment. A bone
      marrow aspirate can be applied, but it may not provide a sufficient number of
      MSCs. In addition to autologous bone grafts, the best collagen production was on
      allografts. In bone graft substitutes, the porous structure played an important
      role because on a non-porous material (calcium sulphate) the formation of
      collagen was very low. There was no difference in collagen and extracellular
      mineralized matrix production between whole bone marrow and monocyte
      concentrates. CONCLUSIONS: Elderly patients have reduced bone healing capacity
      also because of osteopenia/osteoporosis that occurs more often than it is
      generally diagnosed, including its coincidence with osteoarthritis. The
      mesenchymal stem cells isolated from osteopenic bone give a lower number of CFU
      F/ml and have a lower proliferative capacity. Of the matrices for new bone
      formation, allografts showed the best results because collagen was produced
      already in expansion medium. Of the graft substitutes, porous -TCP was the best,
      but with collagen production in differential medium. The use of bone marrow
      aspirate is currently a method of choice in order to increase MSC numbers at the
      site of bone healing. The use of growth factors is an expensive treatment. To
      achieve the goal of reliable promotion of osteogenesis with cultured MSC
      transplantation and use of composite materials with pro-osteogenic and pro
      angiogenic factors will still require many experimental and clinical studies.

PMID- 22405551
TI  - [Closing-wedge valgus high tibial osteotomy].
AB  - PURPOSE OF THE STUDY: The aim of the study was to evaluate the group of patients
      treated for varus arthritic knee by the method of high tibial osteotomy from the
      lateral approach and to assess its role in the present-day orthopaedic surgery
      which also offers other options such as distraction osteotomy from the medial
      approach, autologous chondrocyte transplantation or alloplasty. MATERIAL AND
      METHODS: The study included 101 patients, 41 women and 60 men, undergoing lateral
      valgus high tibial osteotomy at our department between 2003 and 2007. The age of
      patients at the time of surgery ranged from 34 to 61 years, with an average of 54
      years. The follow-up period was in the range of 2 to 7 years, with an average of
      5.2 years. Moderate varus gonarthrosis was the most frequent indication for
      osteotomy. Each procedure was preceded by arthroscopy with treatment of the
      pathologies found; these most frequently included a torn medial meniscus,
      synovitis or medial compartment chondropathy. The outcomes were evaluated using a
      system of clinical and radiographic assessment (A) and the Lysholm score (B)
      before and after surgery. RESULTS: The A system evaluation showed excellent, good
      and poor results in 42, 47 and 12 patients, respectively. The average Lysholm
      score was 51 points before surgery and 73 points at the final follow-up
      examination; the average improvement was by 22 points. The average mechanical
      axis was 2 degrees of varus before and 6 degrees of valgus after surgery. The
      minimal correction of the axis was 4 degrees and the maximal correction was 18
      degrees. The average change of the axis was 8 degrees. Complications were
      recorded in 21% of the patients. None of the patients had delayed healing,
      pseudoarthrosis, fracture of the tibial plateau or peroneal nerve palsy.
      DISCUSSION: Long-term excellent and good outcomes were found more often in the
      patients with a greater resulting valgus angle. After surgery the average
      anatomical axis was 7.4 degrees of valgus for good and excellent results, and 4.3
      degrees of valgus for poor results. This is in agreement with the common
      recommendation that osteotomy should produce mild overcorrection. The 95%
      osteotomy survival rate in this study is in accordance with the results reported
      by Coventry et al. and Sprenger et al. With strict adherence to the indication
      criteria, we did not find any clear relationship between the severity of knee
      injury before surgery and the subjective evaluation of post-operative clinical
      outcome. The patient's body mass index (BMI) had no effect on the outcome, but
      the majority of our patients had a BMI below 30 (average, 28.2). The range of
      motion after surgery was not significantly limited. Both the occurrence of
      complications and alignment maintenance are comparable with the results of
      distraction osteotomy. CONCLUSIONS: The mid-term results of valgus osteotomy
      performed by the technique described by Coventry et al. testify to the lasting
      success of this method. Satisfaction with its outcome can be expected in about
      90% of the patients in a 5-year post-operative period. To achieve this, it is
      necessary to strictly observe the indication criteria, operative technique and
      thorough arthroscopic treatment of the joint. Also, the necessity of slight over
      correction to 8 degrees of valgus is emphasised.

PMID- 22405552
TI  - [The influence of patient age and mechanism of injury on the type of pelvic
      fracture: epidemiological study].
AB  - PURPOSE OF THE STUDY: The patients with pelvic ring injury involve two groups: 1)
      young and middle-age persons, mostly men, with serious injury to the pelvic ring
      due to high-energy trauma; and 2) older patients, mostly women, with osteoporotic
      fractures due to a simple fall. The aim of this study was to show significant
      differences in the selected epidemiological characteristics between these two
      groups. MATERIAL AND METHODS: The group comprised 225 patients older than 15
      years with pelvic fractures who were treated between January 1, 2007, and
      December 31, 2009. In this retrospective descriptive study, the patients' data on
      age, gender, mechanism of injury and a type of fracture according to the AO
      classification were retrieved and analysed. Categorical data at a level of
      significance of 5% were compared using the Chi-square test. RESULTS: In the group
      reviewed there were 113 women and 112 men, with an average age of 51 years
      (women, 53 years; men, 49 years) in the range of 15 to 95 years. More men than
      women were in the age range of 15 to 60 years (with the difference being
      significant only in the sixth decade of life; p=0.043). In the age category of
      over sixty, women outnumbered men, and this was significant in the eight and
      ninth decades (p=0.023 and p=0.04, respectively). Significantly more men were
      involved in motorbike accidents (p=0.047) or had falls from heights (p=0.004) and
      particularly those at a worksite (p<0.001). Fractures due to a simple fall were
      significantly more frequent in women than men (p<0.001) and, generally, were most
      often found in the old-age category, in which women were eight years senior to
      men. Type A fractures were found in 58, type B fractures in 140 and type C
      fractures in 27 patients. The most frequent fractures (A2.2, p=0.054; B2.1,
      p=0.038) occurred more often in women and at a much higher age than in men (the
      age difference was 15 years in type A2.2 fractures and "only" 7 years in type
      B2.1 fractures). The patients who sustained either of these fractures in a simple
      fall were about 35 years older than those in whom these fractures were caused by
      high-energy trauma. DISCUSSION: The fact that pelvic injuries most often occur in
      men at young or middle age has been confirmed by several epidemiological studies
      with a conclusion that age-related risky male behaviours play a significant role.
      The findings of this study showed that pelvic fractures due to simple falls were
      mostly found in old-age patients, with women eight years older than men. This
      provides evidence for the existence of two distinct groups of patients with
      pelvic fractures. The existence of two epidemiologically different groups of
      patients with pelvic fractures, in the authors' opinion, is demonstrated by a
      correlation of AO fracture type, patient gender and age in each group. A mere
      comparison of the age of patients indicates that older patients had mostly type A
      and B fractures. Unilateral fractures of the pubic ramus after a simple fall,
      which are regarded as related to osteoporosis, were recorded in a significantly
      higher number of women of the oldest age. The authors suggest that
      epidemiological studies of pelvic injuries should use the age of 70+ as an
      exclusion criterion in the patients with type A2.2 and B2.1 fractures. This will
      remove the bias of epidemiological data on patients with severe pelvic injuries,
      resulting from involvement of patients with osteoporotic fractures. CONCLUSION:
      The evaluation of epidemiological data in this study allows us to conclude that
      younger men are those most frequently sustaining pelvic injuries due to high
      energy trauma and that old age (80+) is characteristic for patients of both
      sexes, with female sex predominance, who have fractures due to simple falls.
      These findings give support to the concept that, in a group of patients with
      pelvic injuries, a subgroup with fractures different in terms of epidemiology and
      aetiology (osteoporotic fracture) can be identified.

PMID- 22405553
TI  - [Dens fracture with concurrent subaxial cervical spine injury in patients with
      ankylosing spondylitis].
AB  - Odontoid process fractures in patients with ankylosing spondylitis (AS) are rare
      and their finding together with subaxial cervical spine injury is a great
      exception. Neither the mechanism of such a combined cervical spine injury nor its
      surgical treatment has so far been reported in the relevant literature (MEDLINE).
      The authors present two such cases, one in a 30- and the other in a 74-year-old
      man. Both AS patients showed a common mechanism of injury sustained in a car
      accident, which involved hitting a solid barrier at 60 to 70 kilometres per hour,
      resulting in hyperextension of the cervical spine. In both patients the fractures
      were stabilised from the anterior approach: the dens fractures with one or two
      screws by the Magerl-Bohler method and the subaxial fractures with long-plate and
      screw fixation. At 2 post-operative years complete bone union of the subaxial
      spine was recorded in both patients; complete healing of the dens fracture was
      achieved in one patient while in the other partial fibrous union of the dens
      fracture occurred.

PMID- 22405554
TI  - [Bilateral arthrodesis of the medial foot joints in a patient with rheumatoid
      arthritis].
AB  - Patients with rheumatoid arthritis (RA) often have foot problems. The subtalar
      and particularly talonavicular joints are affected most frequently. The posterior
      tibial tendon has an important role in mid-foot stability. In RA patients,
      chronic inflammation of this tendon or talonavicular joint arthritis can results
      in posterior tibial tendon rupture. This leads to a collapsed talonavicular joint
      and forefoot instability, first with talonavicular and later Chopart's joint
      involvement. This shows as a planovalgus foot, with the forefoot in pronation and
      the heel in valgus deviation. In a 61-year-old RA patient, ruptures of the
      posterior tibial tendon due to rheumatoid inflammation occurred bilaterally, with
      subsequent deviation and instability of the forefoot. Arthrodesis with a medial
      column screw-Midfoot Fusion Bolt was carried out on the left foot and 4 months
      later on the right foot. At 7 months after the left and 4 months after the right
      foot surgery, the patient was free from pain, both feet were stable under loading
      and the forefoot was firm. The planovalgus deformity was corrected, as well as a
      valgus deviation of the great toe. Radiography showed a good position of the
      screws and complete healing of the medial foot joints.

PMID- 22405555
TI  - [Talus partitus. A case report].
AB  - An ankle bone consisting of several fragments is a rare anatomical variant of the
      talus, in the literature described as talus partitus or frontal split. On
      radiographs or CT scans it presents as two or more relatively large fragments.
      The term talus partitus is sometimes incorrectly used for an accessory bone that
      occasionally develops behind the ankle bone and is called os trigonum. Talus
      partitus is an unusual developmental anomaly in which the talus is partitioned
      although it ossifies from a single centre. The cause of its split has not been
      explained although this may also be due to a previous unrecognized injury. In the
      Slovak medical literature no report of this anomaly has been found. Here we
      resent the case of a 30-year-old man in whom the ankle bone split was an
      incidental finding. This patient also had ipsilateral developmental dysplasia of
      the hip. This is the first report of a patient with the two concurrently found
      anomalies.

PMID- 22405556
TI  - Debunking the myth of the periosteum.

PMID- 22405557
TI  - An assessment of prime-boost vaccination schedules with AS03A -adjuvanted
      prepandemic H5N1 vaccines: a randomized study in European adults.
AB  - BACKGROUND: Long-term persistence of immune response and safety of an H5N1
      prepandemic influenza vaccine adjuvanted with AS03 (an alpha-tocopherol oil-in
      water emulsion-based adjuvant system) was evaluated using various prime-boost
      schedules that mimicked potential pandemic scenarios (NCT00430521). METHODS: Five
      hundred and twelve healthy adults aged 18-60 years received primary vaccination
      with one or two doses (0, 21 days schedule) of the A/Vietnam/1194/2004 H5N1
      vaccine followed by a booster dose (A/Vietnam/1194/2004 or A/Indonesia/05/2005
      strain) six or twelve months later across eight randomized groups. Immunogenicity
      results by hemagglutination inhibition [HI] assay, microneutralization assay, and
      the cell-mediated immune response (CMI) are reported here for the four groups
      boosted at Month 12. RESULTS: A one-dose-adjuvanted primary administration
      followed 12 months later by a single-adjuvanted booster dose containing a
      heterologous vaccine strain met or exceeded all US and European criteria for both
      strains. Increasing the interval between the first and second dose (from 21 days
      to 12 months) resulted in stronger cross-reactive immune responses against the
      A/Indonesia/05/2005 strain. The HI antibody response against the two strains
      persisted for 6 months after the booster dose irrespective of the booster
      vaccine's strain. The neutralizing antibody responses and the CMI observed in the
      study population paralleled the HI immune response. Overall, the vaccine had a
      clinically acceptable safety profile. CONCLUSION: The H5N1 vaccine in this study
      allowed for flexibility in the time interval between primary and booster
      vaccination and the use of a heterologous strain without impacting the strength
      of the humoral and cellular immune response to both vaccine strains.

PMID- 22405558
TI  - Tentative identification of phase I metabolites of HU-210, a classical synthetic
      cannabinoid, by LC-MS/MS.
AB  - (6aR,10aR)-9-(Hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a
      tetrahydrobenzo[c]chromen-1-ol (HU-210) is a synthetic cannabinoid, with a
      classical cannabinoid structure similar to Delta(9)-tetrahydrocannabinol
      (Delta(9)-THC). In this study, the in vitro metabolism of HU-210 was investigated
      in human liver microsomes to characterize associated phase I metabolites. HU-210
      was incubated with human liver microsomes, and the reaction mixture was analyzed
      using LC-MS/MS. HU-210 was metabolized in human liver microsomes, yielding about
      24 metabolites. These metabolites were structurally characterized on the basis of
      accurate mass analyses and MS/MS fragmentation patterns. The major metabolic
      route for HU-210 was oxygenation. Metabolites M1-M7 were identified as mono
      oxygenated metabolites; M8-M15, mono-hydroxylated metabolites; M16-M20, di
      oxygenated metabolites; and M21-M24, di-hydroxylated metabolites. These results
      provide evidence for in vivo HU-210 metabolism, and they may be applied to the
      analysis of HU-210 and its relevant metabolites in biological samples.

PMID- 22405559
TI  - Whole parasite vaccination approaches for prevention of malaria infection.
AB  - Malaria is caused by complex protozoan Plasmodium parasites that have foiled
      efforts to develop a protective vaccine. Despite this, it has been known for more
      than 40 years that immunization with radiation-attenuated, whole Plasmodium
      sporozoites confers complete protection against malaria challenge. This model
      gave the rationale for development of recombinant and vectored subunit
      vaccination strategies that have, however, not yet matched whole sporozoite
      protective efficacy. Novel attenuation and immunization approaches for whole
      sporozoite vaccination and a deeper understanding of cellular and humoral
      protective immune responses that eliminate pre-erythrocytic stages are paving the
      way for the development of next-generation vaccination strategies that completely
      prevent malaria.

PMID- 22405560
TI  - A new process for nickel ammonium disulfate production from ash of the
      hyperaccumulating plant Alyssum murale.
AB  - The extraction of nickel (Ni) from ultramafic soils by phytomining can be
      achieved using Alyssum murale cultures. This study presents a new process for the
      valorization of Ni accumulated by this plant through the production of a Ni
      ammonium disulfate salt (Ni(NH(4))(2)(SO(4))(2).6H(2)O). The process comprises an
      initial leaching of the ashes of A. murale with a sulphuric acid solution (1.9 M
      H(2)SO(4), T=95  degrees C, t=240 min, TS=150 g ash L(-1)), producing a leachate
      rich in Ni (10.2 g Ni L(-1); 96% Ni solubilisation), Mg, P, K, Fe, Ca and Al. The
      pH of the acid leachate is increased to 5.0 with NaOH (5M), followed by an
      evaporation step which produced a purified solution rich in Ni (21.3 g NiL(-1))
      and an iron hydroxide precipitate. The cold crystallization (T=2  degrees C,
      t=6h) of this solution by the stoichiometric addition (* 1.2) of ammonium sulfate
      generates a Ni ammonium disulfate salt, containing 13.2% Ni, that is potentially
      valuable to industry.

PMID- 22405562
TI  - Characterization of airborne particles in an open pit mining region.
AB  - We characterized airborne particle samples collected from 15 stations in
      operation since 2007 in one of the world's largest opencast coal mining regions.
      Using gravimetric, scanning electron microscopy (SEM-EDS), and X-ray
      photoelectron spectroscopy (XPS) analysis the samples were characterized in terms
      of concentration, morphology, particle size distribution (PSD), and elemental
      composition. All of the total suspended particulate (TSP) samples exhibited a log
      normal PSD with a mean of d=5.46 +/- 0.32 MUm and sigma(ln d)=0.61 +/- 0.03.
      Similarly, all particles with an equivalent aerodynamic diameter less than 10 MUm
      (PM(10)) exhibited a log-normal type distribution with a mean of d=3.6 +/- 0.38
      MUm and sigma(ln d)=0.55 +/- 0.03. XPS analysis indicated that the main elements
      present in the particles were carbon, oxygen, potassium, and silicon with average
      mass concentrations of 41.5%, 34.7%, 11.6%, and 5.7% respectively. In SEM
      micrographs the particles appeared smooth-surfaced and irregular in shape, and
      tended to agglomerate. The particles were typically clay minerals, including
      limestone, calcite, quartz, and potassium feldspar.

PMID- 22405561
TI  - The relationship between exposure to microbial volatile organic compound and
      allergy prevalence in single-family homes.
AB  - Microbial volatile organic compounds (MVOCs) are a type of VOCs produced by
      microorganisms. Exposure to 1-octen-3-ol, one of the known MVOCs, has been
      reported to reduce nasal patency and increase nasal lavage myeloperoxidase,
      eosinophil cationic proteins, and lysozymes in both experimental and field
      studies. We reported in a previous paper that 1-octen-3-ol exposure at home is
      associated with mucosal symptoms. In this study, our aim was to investigate the
      relationship between asthma and allergies and MVOC exposure in single-family
      homes. The subjects were 624 inhabitants of 182 detached houses in six regions of
      Japan. Air samples were collected using diffusive samplers, and the
      concentrations of eight selected MVOCs were analyzed using gas
      chromatography/mass spectrometry in selected-ion-monitoring mode. Each inhabitant
      of each of the dwellings was given a self-administered questionnaire. Among the
      609 subjects who answered all of the questions about allergies, history of the
      medical treatment for asthma, atopic dermatitis, allergic rhinitis, and allergic
      conjunctivitis within the preceding two years was 4.8%, 9.9%, 18.2%, and 7.1%,
      respectively. A significant association between 1-octen-3-ol (per log(10) unit)
      and allergic rhinitis odds ratio (OR): 4.10, 95% confidence interval (CI): 1.71
      to 9.80 and conjunctivitis (OR: 3.54, CI: 1.17 to 10.7) was found after adjusting
      for age, sex, tobacco, wall-to-wall carpeting, signs of dampness, history of
      treatment for hay fever, and other potentially relevant environmental factors. No
      relationships were found between any MVOCs and asthma or atopic dermatitis after
      the adjustment. The levels of MVOCs and airborne fungi were only weakly
      correlated. These results are consistent with previous studies that have
      associated higher levels of 1-octen-3-ol exposure with increased irritation of
      nasal and ocular mucosae. Although the indoor-air concentrations of 1-octen-3-ol
      found in this study were relatively low, we conclude that exposure to MVOC may be
      related to rhinitis and conjunctivitis.

PMID- 22405563
TI  - Facile method for synthesis of hollow porous magnetic microspheres with
      controllable structure.
AB  - Hollow porous magnetic microspheres with strong magnetization and controllable
      structure were prepared via a facile electrostatic self-assembly of the
      positively charged Fe(3)O(4) nanoparticles onto the surface of the negatively
      charged poly(N,N'-methylenebisacrylamide-co-methacrylic acid) (P(MBAAm-co-MAA))
      microspheres with subsequent removal of the polymer core through calcination at
      high temperature. The shell thickness was facilely tuned through the ratio
      between Fe(3)O(4) and polymer, and the void space was conveniently changed
      through the size of polymer microspheres. The hollow magnetic microspheres
      possessed high saturation magnetization value (51.38 emu/g) and porous structure
      with high specific surface area (108.04 m(2)/g). Based on these properties, the
      drug loading and release behaviors were investigated, which indicated that the
      hollow magnetic microspheres exhibited a controlled release process.

PMID- 22405564
TI  - Synthesis and characterization of polymer-protected rhodium and palladium sols in
      mixed media.
AB  - A series of polymer-protected rhodium and palladium sols were generated in mixed
      (organic/aqueous) dispersion media. Protecting polymers used were PAA, PVP, PVA
      and an oligosaccharide-based protecting agent, arabinogalactan. This is the first
      systematic study of colloids generated in mixed solvent dispersion media with
      these protecting agents. The sols were characterized by TEM, UV/Vis
      spectrophotometry and Photon Correlation Spectroscopy (PCS). In general, the
      macroscopic stability of the sols depended on the protecting agent/organic
      cosolvent combination used, with a nonlinear dependence on cosolvent
      concentration. Observed sol stabilities correlated well with pre-existing
      hydrodynamic data for the protective polymers, e.g. radius of gyration data.
      Average particle size and polydispersity of all sols examined decreased as
      cosolvent concentration increased, with actual cosolvent concentration,
      protecting agent and reducing agent used influencing the extent of decrease. Sol
      particle sizes ranged from 0.8 nm to 6.0 nm with sol turbidities decreasing in
      parallel with the particle sizes. Hydrodynamic sizes (from PCS) tended to reflect
      the sols' macroscopic stabilities. FTIR studies using adsorbed CO as a
      spectroscopic surface probe indicated decreases in the nu(CO)(ads) stretching
      frequency with an increase in cosolvent concentration due to competitive
      adsorption of CO with the cosolvent molecules on the metal colloid surfaces.

PMID- 22405565
TI  - The effect of pH on charge, swelling and desorption of the dispersant
      poly(methacrylic acid) from poly(methyl methacrylate) microcapsules.
AB  - Poly(methyl methacrylate) microcapsules have been prepared using the solvent
      evaporation technique with poly(methacrylic acid) (PMAA) as dispersant. The
      charge, swelling and desorption of PMAA from the microcapsules after treating the
      suspension with base have been followed using microelectrophoresis, X-ray
      photoelectron spectroscopy and quartz crystal microbalance with dissipation
      monitoring on model PMMA surfaces. Basic treatment of the microcapsule suspension
      leads to temporary colloidal stability through the introduction of charges on the
      PMAA chain. However, the increase in charge causes a continuous desorption of
      PMAA from the microcapsule surface, eventually leading to aggregation. If instead
      poly(diallyldimethylammonium chloride) is added to the base treated microcapsule
      suspension, good colloidal stability is obtained.

PMID- 22405567
TI  - Non-small cell lung carcinoma of donor origin after bilateral lung
      transplantation.

PMID- 22405566
TI  - B-cell activity in children with malaria.
AB  - BACKGROUND: Recent studies implicate deficiency of red blood cell (RBC)
      complement regulatory proteins (CR1 and CD55) in the pathogenesis of malarial
      anaemia. This study explored the involvement of B cell CD21, which has an
      analogous role to RBC CR1. METHODS: In a case control study conducted in Kisumu
      District hospital, western Kenya, children with severe malaria anaemia (SMA) and
      those with uncomplicated malaria (UM) were assessed by flow cytometry for B cells
      (CD20+) numbers, expression levels of CD21 and deposition of C3dg and by ELISA
      for soluble CD21 (sCD21). Paired t tests were used to determine statistical
      significance at a = 0.05. RESULTS: Children with SMA had significantly higher
      lymphocyte count (9,627.7 +/- 8786.1 SD vs. 5,507 +/- 2436 SD, P = 0.04 in the UM
      group) and the computed geometric mean of mature B-cell numbers based on the
      absolute lymphocyte count was significantly higher for SMA group: 1,823 (1,126 to
      2,982, 95% CI) and 826.6 (564 to 1,220, 95% CI)] for UM group (P = 0.003). SMA
      group also had a higher percentage of CD20+ B cells (26.8 +/- 9.7SD vs 20.9 +/-
      9.01 SD in the UM) (P = 0.03), indicating considerable polyclonal B-cell
      activation. The CD21 median flourescence intensity was lower in the SMA (246.4 +/
      87.4 SD vs 369 +/- 137.7 SD) (P <0.0001), probably due to complement mediated
      shaving of CD21 by fixed tissue macrophages. The CD20+ B cells of SMAs had higher
      levels of the complement split product C3dg (18.35 +/- 10 SD vs 11.5 +/- 6.8
      S.D), (P = 0.0002), confirming possible role of complement in CD21 removal.
      Unexpectedly, the SMAs had lower levels of sCD21 (226.5 +/- 131.5 SD vs 341.4 +/-
      137.3 SD in the UM) (P < 0.0001), indicating that the shaved CD21 is not released
      to peripheral circulation. CONCLUSIONS: These results implicate B-cell in
      pathophysiology of severe malaria that involves increased B-cell proliferation,
      increased complement deposition and subsequent loss of membrane-bound CD21. The
      loss of CD21 is not by the classical enzmatic cleavage.

PMID- 22405568
TI  - Pemetrexed as a possible cause of severe rhabdomyolysis in the treatment of lung
      cancer.
AB  - According to many published clinical trials, both haematological and non
      haematological toxicities resulting from pemetrexed were relatively mild and
      therefore this drug is considered to be well tolerated. We came across a 60 y/o
      woman patient with stage IV adenocarcinoma, suffered from unexpected life
      threatening complication, rhabdomyolysis. Severe lower leg weakness and
      respiratory failure occurred on the day 3 after pemetrexed administration. To the
      best of our knowledge, this is the first report that addresses severe and life
      threatening rhabdomyolysis which occur during chemotherapy for the treatment of
      lung cancer. We believed pemetrexed is a safe drug but we should pay attention to
      possible complications related to pemetrexed-based treatment and to also treat
      the life-threatening disorder of rhabdomyolysis immediately to prevent further
      damage.

PMID- 22405569
TI  - Oncologists' assessments of lung cancer patient and family disagreements
      regarding treatment decision making.
AB  - BACKGROUND: Disagreements between cancer patients and their caregivers about
      treatment and care can affect the patient's physical and mental well-being.
      Therefore it is important to understand if oncologists can accurately identify
      the presence of patient-caregiver decisional conflict. This study examined
      assessments made by lung cancer patients, their caregivers, and their oncologists
      regarding patient-caregiver disagreements concerning treatment and care
      decisions. PARTICIPANTS AND METHODS: We assessed the extent to which the patient,
      caregiver, and oncologist reported disagreement between the patient and the
      family member regarding treatment decisions in 134 patient-caregiver-oncologist
      triads. Descriptive statistics were used to explore rates of concordance amongst
      all possible combinations of raters. Loglinear models were tested for 3-way
      agreement. RESULTS: Most patient-caregiver pairs, 82.1% (n = 110), reported
      agreement concerning presence or absence of decisional conflict. Oncologists were
      more successful in detecting absence of conflict than the presence of conflict.
      When the caregiver and the oncologist agreed, it was regarding the absence of
      conflict (64.9%), rather than the presence of conflict. In 10.6% (n = 15) of
      cases, oncologists reported that conflictual relationships negatively impacted
      their ability to provide patient care. CONCLUSIONS: Recent models of cancer
      patient care promote including the caregiver fully in the process while
      respecting the primacy of the patient's perspective. However, these models assume
      that the oncologist will recognize when disagreements exist and be able to assist
      in conflict resolution. The degree to which the oncologist identified that
      conflict exists and implications for their ability to provide patient care when
      familial disagreements existed are discussed.

PMID- 22405571
TI  - Two-timing zinc finger transcription factors liaising with RNA.
AB  - Classical zinc fingers (ZFs) are one of the most common protein domains in higher
      eukaryotes and have been known for almost 30 years to act as sequence-specific
      DNA-binding domains. This knowledge has come, however, from the study of a small
      number of archetypal proteins, and a larger picture is beginning to emerge that
      ZF functions are far more diverse than originally suspected. Here, we review the
      evidence that a subset of ZF proteins live double lives, binding to both DNA and
      RNA targets and frequenting both the cytoplasm and the nucleus. This duality can
      create an important additional level of gene regulation that serves to connect
      transcriptional and post-transcriptional control.

PMID- 22405570
TI  - A multicenter phase II randomized trial of gemcitabine followed by erlotinib at
      progression, versus the reverse sequence, in vulnerable elderly patients with
      advanced non small-cell lung cancer selected with a comprehensive geriatric
      assessment (the GFPC 0505 study).
AB  - BACKGROUND: The aim of this randomized phase II trial was to evaluate the
      feasibility and activity of weekly gemcitabine (G) followed by erlotinib at
      disease progression (arm A) versus erlotinib followed by G at progression (arm B)
      in vulnerable elderly patients with advanced non small-cell lung cancer (NSCLC),
      selected on the basis of a comprehensive geriatric assessment (CGA). METHODS:
      Vulnerable elderly chemotherapy-naive patients with stage IIIB/IV NSCLC were
      selected after a CGA (socioeconomic, cognitive and emotional status, depression,
      nutritional status, ADL and IADL assessments). The primary endpoint was the time
      to second progression (TTP2). Overall survival (OS), time to first progression
      (TTP1) and safety were secondary endpoints. RESULTS: Between May 2006 and January
      2010, 21 centers enrolled 100 patients, of whom 94 were eligible. TTP2 was 4.3
      and 3.5 months in arm A and arm B, respectively; TTP1 was 2.5 and 2.2 months; and
      the median OS time was 4.4 and 3.9 months. The respective one-year survival rates
      were 27.3% and 20%. There was no major unexpected toxicity. CONCLUSION: In
      vulnerable elderly patients with NSCLC not selected for EGFR expression, both
      strategies were feasible but had modest efficacy. Further studies are needed to
      identify elderly patients who should receive palliative care only.

PMID- 22405572
TI  - Protein N-terminal acetyltransferases: when the start matters.
AB  - The majority of eukaryotic proteins are subjected to N-terminal acetylation (Nt
      acetylation), catalysed by N-terminal acetyltransferases (NATs). Recently, the
      structure of an NAT-peptide complex was determined, and detailed proteome-wide Nt
      acetylation patterns were revealed. Furthermore, Nt-acetylation just emerged as a
      multifunctional regulator, acting as a protein degradation signal, an inhibitor
      of endoplasmic reticulum (ER) translocation, and a mediator of protein complex
      formation. Nt-acetylation is regulated by acetyl-coenzyme A (Ac-CoA) levels, and
      thereby links metabolic cell states to cell death. The essentiality of NATs in
      humans is stressed by the recent discovery of a human hereditary lethal disease
      caused by a mutation in an NAT gene. Here, we discuss how these recent findings
      shed light on NATs as major protein regulators and key cellular players.

PMID- 22405573
TI  - Hair and scalp dermatoscopy.
AB  - Dermatoscopy is a noninvasive diagnostic tool that allows the recognition of
      morphologic structures not visible by the naked eye. Trichoscopy (scalp
      dermatoscopy and videodermatoscopy) is useful for the diagnosis and follow-up of
      hair and scalp disorders. However, it is not widely used in the management of
      hair disorders. This review provides updated information from the literature and
      our experience on the dermoscopic features of the most common hair and scalp
      disorders. This will enable dermatologists to make fast diagnoses of tinea
      capitis and alopecia areata, distinguish early androgenetic alopecia from telogen
      effluvium, and differentiate scarring from nonscarring alopecia.

PMID- 22405574
TI  - Tissue-type-specific transcriptome analysis identifies developing xylem-specific
      promoters in poplar.
AB  - Plant biotechnology offers a means to create novel phenotypes. However,
      commercial application of biotechnology in crop improvement programmes is
      severely hindered by the lack of utility promoters (or freedom to operate the
      existing ones) that can drive gene expression in a tissue-specific or temporally
      controlled manner. Woody biomass is gaining popularity as a source of fermentable
      sugars for liquid fuel production. To improve the quantity and quality of woody
      biomass, developing xylem (DX)-specific modification of the feedstock is highly
      desirable. To develop utility promoters that can drive transgene expression in a
      DX-specific manner, we used the Affymetrix Poplar Genome Arrays to obtain tissue
      type-specific transcriptomes from poplar stems. Subsequent bioinformatics
      analysis identified 37 transcripts that are specifically or strongly expressed in
      DX cells of poplar. After further confirmation of their DX-specific expression
      using semi-quantitative PCR, we selected four genes (DX5, DX8, DX11 and DX15) for
      in vivo confirmation of their tissue-specific expression in transgenic poplars.
      The promoter regions of the selected DX genes were isolated and fused to a beta
      glucuronidase (GUS)-reported gene in a binary vector. This construct was used to
      produce transgenic poplars via Agrobacterium-mediated transformation. The GUS
      expression patterns of the resulting transgenic plants showed that these
      promoters were active in the xylem cells at early seedling growth and had
      strongest expression in the developing xylem cells at later growth stages of
      poplar. We conclude that these DX promoters can be used as a utility promoter for
      DX-specific biomass engineering.

PMID- 22405575
TI  - Effects of lumbar extensor fatigue and surface inclination on postural control
      during quiet stance.
AB  - A number of work environments require workers to perform tasks on inclined
      surfaces. Such tasks, along with muscle fatigue, can impair postural control and
      increase falling risks. The objective of this study was to determine the effects
      of surface inclination angle, standing direction, and lumbar extensor fatigue on
      postural control during quiet standing. A group of 16 young, healthy participants
      were tested while standing on inclined surfaces before and after lumbar extensor
      fatigue (induced by repetitive isotonic exercise). Three inclination angles (0
      degrees , 18 degrees  and 26 degrees ) and three standing directions (uphill,
      downhill, and lateral facing) were examined. Postural control was assessed using
      several measures derived from center-of-pressure time series and subjectively
      perceived stability. Significant main and interactive effects of inclination
      angle and standing direction were found for all dependent measures. The adverse
      effects of standing on inclined surfaces were found to differ between the three
      standing directions. In general, dose-response relationships with inclination
      angle were evident, particularly in the lateral-facing direction. Fatigue-related
      effects differed between conditions, suggesting that the adverse effect of lumbar
      extensor fatigue on postural control depend on inclination angle and standing
      direction. These findings may facilitate the development of fall prevention
      interventions for work involving inclined surfaces.

PMID- 22405576
TI  - Asymptomatic pneumomediastinum after wisdom tooth extraction.

PMID- 22405577
TI  - Why have sustained increases in obesity and type 2 diabetes not offset declines
      in cardiovascular mortality over recent decades in Western countries?
AB  - The majority of Western countries have reported large falls in cardiovascular
      diseases (CVD) mortality rates since the 1970s. Yet since the 1980s, they have
      also experienced two-fold or three-fold increases in the prevalence of obesity
      and type 2 diabetes--both considered substantial risk factors for CVD. So why
      have these increasing risks apparently not impacted on CVD mortality falls? This
      viewpoint outlines the main factors involved; examines recent trends and apparent
      contradictions; offers some explanations for the trends; discusses how more
      usefully complex epidemiological models might lead to clearer evidence; offers
      some explanations for the trends; and explores the implications for CVD
      prevention.

PMID- 22405578
TI  - Assisting the diagnosis of overt hypothyroidism with pattern recognition methods,
      making use of a set of routine tests, and their multiple correlation with total
      T4.
AB  - In our previous papers we proposed a novel screening method that assists the
      diagnosis of patients with overt Graves' hyperthyroidism by making use of routine
      test data and pattern recognition methods. This method can be applied by non
      specialists during physical check-ups at low cost and is expected to lead to
      rapid referrals for examination and treatment by thyroid specialists, that is, to
      improve patients' QOL. In this report, we investigate whether a similar screening
      method is also applicable for overt hypothyroidism. Fifty-six subjects with 12
      routine test data with a known diagnosis (30 patients with overt hypothyroidism
      and 52 healthy female volunteers, and 26 patients with overt hypothyroidism and
      48 healthy male volunteers) were used as training data. Then, test samples of
      patients who had also undergone the same routine tests at the Tohoku university
      hospital were screened by our method for overt hypothyroidism. The present
      examination of the screening method showed its high screening ability with the
      set of four parameters used (lactate dehydrogenase [LDH], total cholesterol [TC],
      red blood cell [RBC] and serum creatinine [S-Cr]). It was found that there was a
      strong multiple correlation between the set of routine test parameters and serum
      total thyroxine (TT4) in the patients with overt hypothyroidism, which supports
      the usefulness of our screening method.

PMID- 22405579
TI  - Comparison and evaluation of the current staging of cutaneous carcinomas.
AB  - BACKGROUND: Recently the "Union for International Cancer Control" (UICC) and the
      "American Joint Committee on Cancer" (AJCC) changed their TNM (tumor, node,
      metastasis) classification of cutaneous carcinomas. METHODS: We compared these
      classifications, tested their practicability with 615 prospectively collected,
      unselected, primary cutaneous squamous cell carcinomas, and introduced additional
      classification criteria. RESULTS: Neither classification contains information
      about prognosis. Non-metastasizing types of cutaneous carcinoma should be
      excluded. The vermilion border of the lower lip and the eyelids should be
      included. Both systems have been improved, but in part they are irreproducible.
      The AJCC has introduced six "high-risk features" to differentiate between T1 and
      T2. However, this does not seem reasonable. Only rare cases are classified as T4.
      Both systems have different N classifications. A clinical cT classification based
      on tumor size 2 cm seems reasonable but not sufficient. It should be complemented
      by a postoperative p (pathologic) T classification based on tumor thickness: "no
      risk"<= 2 mm thickness (0% risk of metastasis), "low risk" > 2 mm to 6 mm
      thickness (4% risk of metastasis), and "high risk" > 6 mm thickness (16% risk of
      metastasis). Immune suppression, poor differentiation/desmoplasia, and the ear as
      tumor site are additional risk factors for metastasis, currently not evaluable.
      CONCLUSIONS: The classifications are unsuitable for a realistic estimate of the
      risk of metastasis which is possible using a combination of tumor size and
      thickness. The N staging system should consider histopathologic findings.

PMID- 22405580
TI  - Effect of poly (ethylene glycol) on coarsening dynamics of titanium dioxide
      nanocrystallites in hydrothermal reaction and the application in dye sensitized
      solar cells.
AB  - Titanium dioxide sols were synthesized by hydrothermal reactions with addition of
      poly (ethylene glycol) (Mw=20,000). Using techniques of X-ray diffraction,
      transmission electron microscopy, dynamic light scattering, and scanning electron
      microscopy, effect of PEG on the crystallographic properties, particle size,
      aggregating behavior, and the morphological properties of nanoparticles in the
      sols were studied. It was found that growth of anatase nanocrystallites was
      retarded by PEG. Average crystallite size of anatase nanocrystallites first
      decreased from 20.7 nm to 10.5 nm as the polymer concentration increased from 1
      g/L to 3 g/L, and then changed little. Meanwhile, small amount of rutile phases
      like rutile nanowires, twin crystallites, and the "flowers" appeared continuously
      when the concentration increased from 3 g/L to 5 g/L. Mono-dispersion was
      obtained with relatively lower PEG concentration. The observed evolvement was
      discussed based on the interaction between the polymers and the nanocrystallites
      with assistance of FTIR. The coverage of polymer chains on surface of
      nanocrystallites leads to isolated reactors, which benefits the uniform
      coarsening rate of the nanocrystallites. The synthesized TiO(2) sols were
      utilized in dye sensitized solar cells. Performance parameters of the solar cells
      were discussed with assistance of dye desorption experiments. The improved
      dispersion in sols was found to benefit the photovoltaic performance of the
      cells.

PMID- 22405581
TI  - Exfoliation of montmorillonite in protein solutions.
AB  - In the study we demonstrate a method to obtain stable, exfoliated montmorillonite
      protein complexes by adsorption of the proteins extracted from hen-egg albumen.
      Analysis of the process by means of sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) revealed that the complexes are formed by sequential
      adsorption of ovotransferrin, ovalbumins, ovomucoid and lysozyme on the surface
      of the silicate. Structural studies performed by X-ray diffraction (XRD) and
      transmission electron microscopy (TEM) indicated that the adsorption of
      ovotransferrin and albumins is accompanied by disintegration of clay stacks into
      discrete platelets. Further analysis by dynamic light scattering (DLS) revealed
      that at protein to silicate weight ratios exceeding 20, the synergistic
      adsorption of albumen components leads to reaggregation of silicate platelets
      into disordered, microgel-like particles. By means of DLS it was found that
      exfoliation predominantly leads to formation of particles with average
      hydrodynamic radii (R(h)) of 0.19 MUm while their aggregation causes formation of
      particles having R(h) in of approx. 0.5 MUm and larger.

PMID- 22405582
TI  - Experimental investigation and population balance equation modeling of solid
      lipid nanoparticle aggregation dynamics.
AB  - Solid lipid nanoparticles (SLNs) have applications in drug delivery and the
      encapsulation of bioactive, lipophilic compounds. However, SLNs tend to aggregate
      when stored due to the lipid crystals undergoing a polymorphic transformation
      from the unstable alpha form to the stable beta form. We developed a population
      balance equation (PBE) model for prediction of average polymorph content and
      aggregate size distribution to better understand this undesirable behavior.
      Experiments with SLNs stored at room temperature showed that polymorphic
      transformation was the rate determining step for our system, SLNs with smaller
      initial size distributions aggregated more rapidly, and aggregates contained
      particles with both alpha and beta crystals. Using parameter values estimated
      from our data, the PBE model was able to capture the bimodal nature of aggregate
      size distributions, the alpha-to-beta polymorph ratio, and the faster aggregation
      dynamics of SLNs with smaller initial size distributions. However, the model was
      unable to adequately capture the fast disappearance rate of primary particles,
      the broad size distributions of formed aggregates, and the significant alpha
      content of aggregating particles. These discrepancies suggest that a PBE model
      which accounts for polymorph content as an internal variable along with aggregate
      size may be required to better reproduce experimental observations.

PMID- 22405583
TI  - Controllable synthesis of aniline oligomers into uniform, dispersed cross and
      needle morphologies.
AB  - Two kinds of homogeneously dispersed aniline oligomer assemblies, namely "cross"
      and "needle" morphologies, can be conveniently synthesized on a large scale in a
      near-neutral aqueous medium using sodium dodecylsulfate (SDS) as a surfactant.
      The effects of oxidant type, premixing time, amount of SDS, monomer
      concentration, and temperature on the final morphology were investigated in
      detail. A possible mechanism for the formation of both "cross" and "needle"
      structures is given.

PMID- 22405584
TI  - Antimicrobial activity of Streptococcus salivarius K12 on bacteria involved in
      oral malodour.
AB  - OBJECTIVE: To investigate the antimicrobial activity of the bacteriocin-producing
      strain Streptococcus salivarius K12 against several bacteria involved in
      halitosis. DESIGN: The inhibitory activity of S. salivarius K12 against
      Solobacterium moorei CCUG39336, four clinical S. moorei isolates, Atopobium
      parvulum ATCC33793 and Eubacterium sulci ATCC35585 was examined by a deferred
      antagonism test. Eubacterium saburreum ATCC33271 and Parvimonas micra ATCC33270,
      which have been tested in previous studies, served as positive controls, and the
      Gram-negative strain Bacteroides fragilis ZIB2800 served as a negative control.
      Additionally, the occurrence of resistance in S. moorei CCUG39336 to S.
      salivarius K12 was analysed by either direct plating or by passage of S. moorei
      CCUG39336 on chloroform-inactived S. salivarius K12-containing agar plates.
      RESULTS: S. salivarius K12 suppressed the growth of all Gram-positive bacteria
      tested, but the extent to which the bacteria were inhibited varied. E. sulci
      ATCC35585 was the most sensitive strain, while all five S. moorei isolates were
      inhibited to a lesser extent. Natural resistance seems to be very low in S.
      moorei CCUG39336, and there was only a slight decrease in sensitivity after
      exposure to S. salivarius K12 over 10 passages. CONCLUSION: Our studies
      demonstrate that S. salivarius K12 has antimicrobial activity against bacteria
      involved in halitosis. This strain might be an interesting and valuable candidate
      for the development of an antimicrobial therapy for halitosis.

PMID- 22405585
TI  - Single-dose inhaled laninamivir: registered in Japan and its potential role in
      control of influenza epidemics.

PMID- 22405586
TI  - Hemostatic properties of a TFPI antibody.
AB  - Bleeds in hemophilia are treated either on demand or prophylactically by
      intravenous replacement therapy with FVIII or FIX. However, there is a call for
      subcutaneous and less frequent drug administration, and this need may be met by
      administration of a suitable antibody. Pioneering studies in vitro] and in a
      rabbit hemophilia model suggest that blockage of tissue factor pathway inhibitor
      (TFPI) provides a potential alternative approach to current therapy of hemophilia
      patients. TFPI down-regulates the initiation of coagulation by inhibition of
      FVIIa/TF/FXa and blockage of TFPI enhances FXa and thrombin generation. In line
      with these discoveries, TFPI targeting reagents with different potential benefits
      are currently evaluated as possible novel therapeutic agents. The development and
      testing of these agents in in vitro and in vivo hemophilia models provide new
      information about the mode of action of TFPI and its role in hemostasis. Blockage
      of TFPI with various antagonists has been shown to effectively enhance FX
      activation by TF/FVIIa and improve clot formation in hemophilia blood and plasma.
      The monoclonal antibody, mAb 2021, is one such antagonist directed towards the
      Kunitz-type protease inhibitor (KPI) 2 domain of TFPI which is now being tested
      in preclinical and clinical trials. Using mAb 2021, we have confirmed the
      original findings, and further characterized the pro-haemostatic effect of this
      specific anti-KPI-2 mAb in preclinical studies.

PMID- 22405587
TI  - Self-defining memories and self-defining future projections in hypomania-prone
      individuals.
AB  - Mania and hypomania involve dysfunctional beliefs about the self, others, and the
      world, as well about affect regulation. The present study explored the impact of
      these beliefs on self-defining memories and self-defining future projections of
      individuals with a history of hypomanic symptoms. The main findings showed that a
      history of hypomanic symptoms was related to enhanced retrieval of memories
      describing positive relationships and to reduced future projections about
      relationships, suggesting both a need for social bonding and a striving for
      autonomy. Moreover, hypomania-prone individuals tended to describe more recent
      events and to produce self-defining memories with references to tension that were
      more integrated in their self-structure. All of these findings support the
      presence of conflicting dysfunctional beliefs and the importance of memories
      containing references to tension in hypomania.

PMID- 22405588
TI  - Acoustic field modeling for physiotherapy ultrasound applicators by using
      approximated functions of measured non-uniform radiation distributions.
AB  - The strongest therapeutic effects in ultrasonic physiotherapy are mainly produced
      at the first centimeters, i.e. close to the applicator surface and, in general,
      only in the near-field zone. The acoustic field produced in practice by this type
      of transducers differs from the classical models because the vibration
      distribution on the real transducer surfaces is non-uniform. However, neither
      models using uniform distribution, nor those using typical non-uniform
      distribution patterns for the source accurately represent the radiation of this
      kind of transducers. Although this therapy is widely used and many efforts have
      been made in experimentally studying the patterns of ultrasound radiation
      produced during physiotherapy applications (IEC-61689, 1998), additional modeling
      researches still would be needed in order to achieve improved models giving field
      patterns closer to the measured ultrasonic results. In this paper, acoustic
      patterns produced from two source radiation functions are proposed and evaluated
      for field modeling of physiotherapy applicators. Both the functions are
      approximations to the pressure distribution measured close to the emitting
      surface and they are based on the modulation of the classical simply-supported
      function using either sinusoidal or Bessel-type distributions. The simply
      supported function is accounted for the radiator-fixing condition and the
      modulation function simulates the complex vibration distribution of this kind of
      transducer. The modulator Bessel function is based on reports about Bessel-type
      vibration distributions found in piezoelectric disk resonators. The use of a
      selected sinusoidal segment represents another analytical option for obtaining an
      approximated behavior of the measured data in a real applicator. Both the field
      models are implemented using the finite element method (FEM) to obtain the
      numerical solution of wave equation at each point in the radiated space. The
      solution is reached by considering axisymmetric radiation in attenuation-free
      media. The results indicate the viability of applying an adequate model for
      acoustic field calculation by simulating the radiating distribution on the
      emitting surface as either sinusoidal or Bessel-modulated functions. Models using
      both the functions describe reasonably real behaviors, but those based on Bessel
      functions are better correlated with the measurements. The results for three
      commercial applicators indicate the possibility of representing, with adequate
      verisimilitude, the acoustic field radiated by physiotherapy ultrasound
      transducers using linear combinations of Bessel profiles describing the radiation
      source.

PMID- 22405589
TI  - Does fibrin sealant use in total knee replacement reduce transfusion rates? A non
      randomised comparative study.
AB  - BACKGROUND: Studies assessing fibrin sealants use during total knee replacement
      (TKR) have produced inconsistent results. We evaluated fibrin sealant therapy in
      TKR procedures performed without tourniquet and without postoperative drains.
      HYPOTHESIS: Use of a fibrin sealant during TKR decreases calculated total blood
      loss, thereby diminishing blood transfusion requirements and costs. PATIENTS AND
      METHODS: We studied 62 patients with primary knee osteoarthritis who underwent
      TKR by the same surgeon between September 2009 and December 2010. Fibrin sealant
      was used only in the last 31 patients, who were compared to the first 31 patients
      regarding calculated total blood loss, blood transfusion rate, and mean number of
      red-blood-cell units used per patient. Costs were compared in the two groups.
      RESULTS: In the control group, mean total blood loss calculated using the method
      of Gross was 1.3+/-0.6 L, 48% of patients required blood transfusions, and the
      mean number of units per patient was 0.9+/-1. In the fibrin-sealant group, 29% of
      patients required blood transfusions and the mean number of units was 0.6+/-0.9.
      The between-group differences in favour of the fibrin-sealant group were not
      statistically significant. In each group, compared with patients not requiring
      blood transfusions, patients needing transfusions had significantly lower
      starting preoperative haemoglobin values and a significantly greater positive
      difference between the calculated total blood loss and the maximum allowable
      blood loss. In the test group, the cost of the 31 units of fibrin sealant was
      9743? and the cost reduction due to using 11 fewer red-blood-cell units was only
      3484?. Hospital stay was not significantly shorter in any of the two groups.
      DISCUSSION: Blood transfusion minimisation during TKR should rely chiefly on
      correcting preoperative anaemia and optimizing transfusion decisions based on the
      difference between the total blood loss and the maximum allowable blood loss.
      Fibrin sealant did not significantly diminish transfusion requirements in our
      study. Randomised studies in larger patient populations are needed. The cost of
      fibrin sealant may exceed the expected cost savings in relation with decreased
      blood transfusion requirements. LEVEL OF EVIDENCE: Level III (before-after
      therapeutic study).

PMID- 22405590
TI  - Pharmacotherapy challenges in patients with first-episode psychosis.
AB  - The first episode of a psychotic disorder typically occurs in late adolescence or
      young adulthood, a critical time of development with respect to personality,
      social role, education, and vocation. The first few years of psychosis appear to
      be a critical period during which intervention needs to be initiated before the
      consequences of psychosis become more severe. Early intervention is therefore
      crucial in maximizing outcomes. Although response rates to antipsychotic
      medication in first-episode psychosis (FEP) are good, there is a relatively high
      risk of relapse. The greatest challenges that physicians face in treating FEP and
      preventing relapse are engaging patients in treatment and preventing non
      adherence to therapy. Overall rates of non-adherence to antipsychotic medications
      for FEP patients are estimated to be at or higher than 50% within the first year
      of treatment, suggesting that malleable factors linked to non-adherence need to
      be targeted in interventions provided. Factors influencing adherence can be
      categorized into four groups: (1) environment-related, (2) patient-related, (3)
      medication-related, and (4) illness-related. This paper will review the factors
      associated with adherence and discuss solutions to optimize engagement, adherence
      to medication, and treatment in order to prevent relapse. Factors like social and
      family support, therapeutic alliance, attitudes and beliefs toward illness and
      medication, insight, substance use disorders, medication efficacy, tolerability,
      and accessibility will be discussed. Solutions, such as early psychosis
      specialized services integrating psychosocial therapies and careful selection of
      appropriate antipsychotic medication, will be proposed.

PMID- 22405591
TI  - The physiological implications of urease inhibitors on N metabolism during
      germination of Pisum sativum and Spinacea oleracea seeds.
AB  - The development of new nitrogen fertilizers is necessary to optimize crop
      production whilst improving the environmental aspects arising from the use of
      nitrogenous fertilization as a cultural practice. The use of urease inhibitors
      aims to improve the efficiency of urea as a nitrogen fertilizer by preventing its
      loss from the soil as ammonia. However, although the action of urease inhibitors
      is aimed at the urease activity in soil, their availability for the plant may
      affect its urease activity. The aim of this work was therefore to evaluate the
      effect of two urease inhibitors, namely acetohydroxamic acid (AHA) and N-(n
      butyl) thiophosphoric triamide (NBPT), on the germination of pea and spinach
      seeds. The results obtained show that urease inhibitors do not affect the
      germination process to any significant degree, with the only process affected
      being imbibition in spinach, thus also suggesting different urease activities for
      both plants. Our findings therefore suggest an activity other than the previously
      reported urolytic activity for urease in spinach. Furthermore, of the two
      inhibitors tested, NBPT was found to be the most effective at inhibiting urease
      activity, especially in pea seedlings.

PMID- 22405592
TI  - The apple WD40 protein MdTTG1 interacts with bHLH but not MYB proteins to
      regulate anthocyanin accumulation.
AB  - The abundance of anthocyanins and proanthocyanins in apples is tightly regulated
      by three classes of regulatory factors, MYB, bHLH and WD40 proteins, only some of
      which have been previously identified. In this study, we identified an apple WD40
      protein (MdTTG1) that promotes the accumulation of anthocyanins. The biosynthetic
      genes required downstream in the flavonoid pathway were up-regulated when MdTTG1
      was over-expressed in Arabidopsis. Consistent with its role as a transcriptional
      regulator, an MdTTG1-GFP fusion protein was observed only in the nucleus. We
      assayed the expression patterns of this gene in different organs and found that
      they were positively correlated with anthocyanin accumulation in the apple. Yeast
      two-hybrid and bimolecular fluorescence complementation assays demonstrated that
      MdTTG1 interacted with bHLH transcription factors (TFs) but not MYB protein,
      whereas bHLH was known to interact with MYB in apples. However, based on a ChIP
      assay, MdTTG1 does not appear to bind to the promoter of the anthocyanin
      biosynthetic genes MdDFR and MdUFGT. Taken together, these results suggest that
      the apple WD40 protein MdTTG1 interacts with bHLH but not MYB proteins to
      regulate anthocyanin accumulation.

PMID- 22405593
TI  - Systematic review of oncological outcomes following surgical management of
      localised renal cancer.
AB  - CONTEXT: Renal cell carcinoma (RCC) accounts for 2-3% of adult malignancies.
      There remain uncertainties over the oncological outcomes for the surgical
      management of localised RCC. OBJECTIVE: Systematically review relevant literature
      comparing oncological outcomes of surgical management of localised RCC (T1
      2N0M0). EVIDENCE ACQUISITION: Relevant databases including Medline, Embase, and
      the Cochrane Library were searched up to October 2010, and an updated scoping
      search was performed up to January 2012. Randomised controlled trials (RCTs) or
      quasi-RCTs, prospective observational studies with controls, retrospective
      matched-pair studies, and comparative studies from well-defined
      registries/databases were included. The main outcomes were overall survival,
      cancer-specific survival, recurrence, and metastases. The Cochrane risk of bias
      tool was used to assess RCTs, and an extended version was used to assess
      nonrandomised studies (NRSs). The quality of evidence was assessed using Grading
      of Recommendations Assessment, Development, and Evaluation (GRADE). EVIDENCE
      SYNTHESIS: A total of 4580 abstracts and 389 full-text articles were assessed.
      Thirty-four studies met the inclusion criteria (6 RCTs and 28 NRSs). Meta
      analyses were planned but were deemed inappropriate due to data heterogeneity.
      There were high risks of bias and low-quality evidence across the evidence base.
      Open radical nephrectomy and open partial nephrectomy showed similar cancer
      specific and overall survival, but when both open and laparoscopic approaches are
      considered together, the evidence showed improved survival for partial
      nephrectomy for tumours <=4cm. The overall evidence suggests either equivalent or
      better survival with partial nephrectomy. Laparoscopic radical nephrectomy
      offered equivalent survival to open radical nephrectomy, and all laparoscopic
      approaches achieved equivalent survival. Open and laparoscopic partial
      nephrectomy achieved equivalent survival. The issue of ipsilateral adrenalectomy
      or complete lymph node dissection with radical nephrectomy or partial nephrectomy
      remains unresolved. CONCLUSIONS: The evidence base suggests localised RCCs are
      best managed by nephron-sparing surgery where technically feasible. However, the
      current evidence base has significant limitations due to studies of low
      methodological quality marked by high risks of bias.

PMID- 22405595
TI  - Chemotography for multi-target SAR analysis in the context of biological
      pathways.
AB  - The increasing amount of chemogenomics data, that is, activity measurements of
      many compounds across a variety of biological targets, allows for better
      understanding of pharmacology in a broad biological context. Rather than
      assessing activity at individual biological targets, today understanding of
      compound interaction with complex biological systems and molecular pathways is
      often sought in phenotypic screens. This perspective poses novel challenges to
      structure-activity relationship (SAR) assessment. Today, the bottleneck of drug
      discovery lies in the understanding of SAR of rich datasets that go beyond single
      targets in the context of biological pathways, potential off-targets, and complex
      selectivity profiles. To aid in the understanding and interpretation of such
      complex SAR, we introduce Chemotography (chemotype chromatography), which encodes
      chemical space using a color spectrum by combining clustering and
      multidimensional scaling. Rich biological data in our approach were visualized
      using spatial dimensions traditionally reserved for chemical space. This allowed
      us to analyze SAR in the context of target hierarchies and phylogenetic trees,
      two-target activity scatter plots, and biological pathways. Chemotography, in
      combination with the Kyoto Encyclopedia of Genes and Genomes (KEGG), also allowed
      us to extract pathway-relevant SAR from the ChEMBL database. We identified
      chemotypes showing polypharmacology and selectivity-conferring scaffolds, even in
      cases where individual compounds have not been tested against all relevant
      targets. In addition, we analyzed SAR in ChEMBL across the entire Kinome, going
      beyond individual compounds. Our method combines the strengths of chemical space
      visualization for SAR analysis and graphical representation of complex biological
      data. Chemotography is a new paradigm for chemogenomic data visualization and its
      versatile applications presented here may allow for improved assessment of SAR in
      biological context, such as phenotypic assay hit lists.

PMID- 22405594
TI  - Viral E3 ubiquitin ligase-mediated degradation of a cellular E3: viral mimicry of
      a cellular phosphorylation mark targets the RNF8 FHA domain.
AB  - Viral hijacking of cellular processes relies on the ability to mimic the
      structure or function of cellular proteins. Many viruses encode ubiquitin ligases
      to facilitate infection, although the mechanisms by which they select their
      substrates are often unknown. The Herpes Simplex Virus type-1-encoded E3
      ubiquitin ligase, ICP0, promotes infection through degradation of cellular
      proteins, including the DNA damage response E3 ligases RNF8 and RNF168. Here we
      describe a mechanism by which this viral E3 hijacks a cellular phosphorylation
      based targeting strategy to degrade RNF8. By mimicking a cellular phosphosite,
      ICP0 binds RNF8 via the RNF8 forkhead associated (FHA) domain. Phosphorylation of
      ICP0 T67 by CK1 recruits RNF8 for degradation and thereby promotes viral
      transcription, replication, and progeny production. We demonstrate that this
      mechanism may constitute a broader viral strategy to target other cellular
      factors, highlighting the importance of this region of the ICP0 protein in
      countering intrinsic antiviral defenses.

PMID- 22405596
TI  - Synthesis and application of an Ndelta-acetyl-Ndelta-hydroxyornithine analog:
      identification of novel metal complexes of deferriferrichrysin.
AB  - Synthesis of Fmoc-protected N(delta)-acetyl-N(delta)-(tert-butoxy)-l-ornithine
      has revealed it to be a metal-chelating amino-acid precursor. This protected
      amino acid was compatible with the preparation of ferrichrome peptides by
      standard Fmoc-based solid-phase peptide synthesis. Evaluation of
      deferriferrichrysin for metal ion chelation revealed that zirconium(IV) and
      titanium(IV) formed complexes with deferriferrichrysin.

PMID- 22405597
TI  - Circulating antimullerian hormone levels in boys decline during early puberty and
      correlate with inhibin B.
AB  - OBJECTIVE: To investigate peripheral levels of inhibin B and antimullerian
      hormone (AMH) in boys during peripuberty and in patients with congenital
      hypogonadotropic hypogonadism (HH). DESIGN: Randomized, placebo-controlled trial
      (peripubertal boys); and cross-sectional clinical study (males with HH). SETTING:
      University central hospital. PATIENT(S): Twenty-eight peripubertal boys with
      idiopathic short stature (ISS), 19 males with Kallmann syndrome. INTERVENTION(S):
      Letrozole (2.5 mg/day) or placebo in boys with ISS for 2 years. MAIN OUTCOME
      MEASURE(S): Longitudinal follow-up observation of serum AMH and its relationship
      with inhibin B during early puberty and the influence of high (letrozole-treated
      boys) and low (males with HH) gonadotropin exposure on circulating AMH.
      RESULT(S): In boys with ISS receiving placebo, the decrease in AMH levels and the
      increase in inhibin B levels were correlated. The serum AMH level had already
      declined before a clinically significant increase in testis volume or serum
      testosterone occurred. Letrozole did not appear to modulate the decline in AMH.
      The AMH levels were lower in boys and young adults with Kallmann syndrome and
      prepubertal testes (mean: 20.9 +/- 4.7 ng/mL, n = 6) as compared with prepubertal
      ISS boys (102.3 +/- 11.9 ng/mL). CONCLUSION(S): The gonadotropin-mediated early
      pubertal increase in inhibin B is tightly coupled to decrease in AMH levels and
      may reflect androgen-mediated differentiation of Sertoli cells. Profound
      gonadotropin deficiency is associated with low AMH levels, suggesting impaired
      development of the Sertoli cell population.

PMID- 22405599
TI  - Emergency testicular sperm extraction after scrotal trauma in a patient with a
      history of contralateral orchiopexy for cryptorchidism: case report and review of
      the literature.
AB  - OBJECTIVE: To report a case of successful testicular sperm extraction performed
      during an emergency scrotal exploration for trauma in a patient with a history of
      previous contralateral cryptorchidism. DESIGN: Case report. SETTING: Clinica
      Urologica I, Universita degli Studi di Milano, Fondazione Istituto di Ricerca e
      Cura a Carattere Scientifico Ca' Granda, Ospedale Maggiore Policlinico.
      PATIENT(S): A 28-year-old man with a history of right orchiopexy for
      cryptorchidism presenting with blunt trauma of the pelvis. INTERVENTION(S):
      Seminiferous tubules extraction. MAIN OUTCOME MEASURE(S): Successful sperm
      retrieval. RESULT(S): Scrotal ultrasonography (US) showed a suspected rupture of
      the left tunica albuginea, and color Doppler examination evidenced testicular
      perfusion only in the region near the mediastinum testis. Twelve hours after
      scrotal exploration, the extracted testicular tissue was successfully processed,
      and seven vials of sperm were frozen. CONCLUSION(S): After testicular trauma in
      selected patients, such as individuals with a history of monorchism or
      cryptorchidism, emergency testicular sperm extraction (TESE) can be a useful
      option to preserve fertility.

PMID- 22405598
TI  - How members of the Society for Reproductive Endocrinology and Infertility and
      Society of Reproductive Surgeons evaluate, define, and manage hydrosalpinges.
AB  - OBJECTIVE: To describe the management of hydrosalpinges among Society for
      Reproduction Endocrinology and Infertility (SREI)/Society of Reproductive
      Surgeons (SRS) members. DESIGN: Cross-sectional survey of SREI/SRS members.
      SETTING: Academic and private practice-based reproductive medicine physicians.
      PARTICIPANT(S): A total of 442 SREI and/or SRS members. INTERVENTION(S): Internet
      based survey. MAIN OUTCOME MEASURE(S): To understand how respondents evaluate,
      define, and manage hydrosalpinges. RESULT(S): Of 1,070 SREI and SRS members
      surveyed, 442 responded to all items, for a 41% response rate. Respondents
      represented both academic and private practice settings, and differences existed
      in the evaluation and management of hydrosalpinges. More than one-half (57%)
      perform their own hysterosalpingograms (HSGs), and 54.5% involve radiologists in
      their interpretation of tubal disease. Most respondents thought that a clinically
      significant hydrosalpinx on HSG is one that is distally occluded (80.4%) or
      visible on ultrasound (60%). Approximately one in four respondents remove a
      unilateral hydrosalpinx before controlled ovarian hyperstimulation
      (COH)/intrauterine insemination (IUI) and clomiphene citrate (CC)/IUI (29.3% and
      22.8%, respectively), and physicians in private practice were more likely to
      intervene (COH: risk ratio [RR] 1.81, 95% confidence interval [CI] 1.31-2.51; CC:
      RR 1.98, 95% CI 1.33-2.95). Although laparoscopic salpingectomy was the preferred
      method of surgical management, nearly one-half responded that hysteroscopic tubal
      occlusion should have a role as a primary method of intervention. CONCLUSION(S):
      SREI/SRS members define a "clinically significant hydrosalpinx" consistently, and
      actual practice among members reflects American Society for Reproductive
      Medicine/SRS recommendations, with variation attributed to individual patient
      needs. Additionally, one in four members intervene before other infertility
      treatments when there is a unilateral hydrosalpinx present.

PMID- 22405600
TI  - Expert recommendations for the laboratory diagnosis of MPS VI.
AB  - Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disease caused by a
      deficiency of N-acetylgalactosamine 4-sulfatase (arylsulfatase B, ASB). This
      enzyme is required for the degradation of dermatan sulfate. In its absence,
      dermatan sulfate accumulates in cells and is excreted in large quantities in
      urine. Specific therapeutic intervention is available; however, accurate and
      timely diagnosis is crucial for maximal benefit. To better understand the current
      practices for diagnosis and to establish diagnostic guidelines, an international
      MPS VI laboratory diagnostics scientific summit was held in February of 2011 in
      Miami, Florida. The various steps in the diagnosis of MPS VI were discussed
      including urinary glycosaminoglycan (uGAG) analysis, enzyme activity analysis,
      and molecular analysis. The following conclusions were reached. Dilute urine
      samples pose a significant problem for uGAG analysis and MPS VI patients can be
      missed by quantitative uGAG testing alone as dermatan sulfate may not always be
      excreted in large quantities. Enzyme activity analysis is universally
      acknowledged as a key component of diagnosis; however, several caveats must be
      considered and the appropriate use of reference enzymes is essential. Molecular
      analysis supports enzyme activity test results and is essential for carrier
      testing, subsequent genetic counseling, and prenatal testing. Overall the expert
      panel recommends caution in the use of uGAG screening alone to rule out or
      confirm the diagnosis of MPS VI and acknowledges enzyme activity analysis as a
      critical component of diagnosis. Measurement of another sulfatase enzyme to
      exclude multiple sulfatase deficiency was recommended prior to the initiation of
      therapy. When feasible, the use of molecular testing as part of the diagnosis is
      encouraged. A diagnostic algorithm for MPS VI is provided.

PMID- 22405601
TI  - Transformation of Mexican lime with an intron-hairpin construct expressing
      untranslatable versions of the genes coding for the three silencing suppressors
      of Citrus tristeza virus confers complete resistance to the virus.
AB  - Citrus tristeza virus (CTV), the causal agent of the most devastating viral
      disease of citrus, has evolved three silencing suppressor proteins acting at
      intra- (p23 and p20) and/or intercellular level (p20 and p25) to overcome host
      antiviral defence. Previously, we showed that Mexican lime transformed with an
      intron-hairpin construct including part of the gene p23 and the adjacent 3'
      untranslated region displays partial resistance to CTV, with a fraction of the
      propagations from some transgenic lines remaining uninfected. Here, we
      transformed Mexican lime with an intron-hairpin vector carrying full-length,
      untranslatable versions of the genes p25, p20 and p23 from CTV strain T36 to
      silence the expression of these critical genes in CTV-infected cells. Three
      transgenic lines presented complete resistance to viral infection, with all their
      propagations remaining symptomless and virus-free after graft inoculation with
      CTV-T36, either in the nontransgenic rootstock or in the transgenic scion.
      Accumulation of transgene-derived siRNAs was necessary but not sufficient for CTV
      resistance. Inoculation with a divergent CTV strain led to partially breaking the
      resistance, thus showing the role of sequence identity in the underlying
      mechanism. Our results are a step forward to developing transgenic resistance to
      CTV and also show that targeting simultaneously by RNA interference (RNAi) the
      three viral silencing suppressors appears critical for this purpose, although the
      involvement of concurrent RNAi mechanisms cannot be excluded.

PMID- 22405602
TI  - Antipsychotics in pediatric and adolescent patients: a review of comparative
      safety data.
AB  - BACKGROUND: Over the past few years, prescriptions of antipsychotic medications
      to children and adolescents have risen significantly. In particular, there is
      increasing use of second- and third-generation antipsychotic agents. However,
      numerous studies have shown clinically-relevant adverse effects (such as weight
      gain, metabolic disorders, prolactin changes, and extrapyramidal symptoms [EPS])
      with these therapeutic agents. Moreover, only a few studies have systematically
      assessed antipsychotics' safety in the pediatric population. The objective of
      this article is to provide a comparative review of the safety data available for
      antipsychotic drug use in pediatric populations. METHODS: A PubMed/MEDLINE search
      was performed for clinical studies that assessed the safety and tolerability of
      first-generation (typical) and second- and third-generation antipsychotics in
      children and adolescents with schizophrenia or bipolar disorder. RESULTS: At
      standard doses, olanzapine and risperidone cause significant weight gain and
      related metabolic complications in patients treated with the medications.
      Quetiapine and ziprasidone display a better tolerability profile than risperidone
      and olanzapine in terms of weight gain, glucose metabolism, increases in
      prolactin levels, and EPS, while aripiprazole seems to be the most weight
      neutral. LIMITATIONS: Most of the studies reviewed had a small sample size, a
      relatively short duration, and a mixed diagnosis population. Systematic analyses
      of antipsychotics' safety in young populations are lacking. CONCLUSIONS: The
      selection of antipsychotics for children and adolescents should include an
      evaluation of their individual therapeutic benefits, safety profiles, and
      approval status for use in the pediatric population. Further research of large
      samples and long-term follow-ups of these patient groups are warranted to help
      predict/manage the occurrence of adverse effects.

PMID- 22405603
TI  - Comparison of early morphological and molecular changes induced by 17-alpha
      methyltestosterone and estradiol benzoate in the rat ovary.
AB  - Repeated exposure to 17-alpha-methyltestosterone (17MT) and estradiol benzoate
      (EB) for 28 or 90 days in rats induce similar ovarian atrophy. The objective of
      the present work was to identify and compare the early effects induced by 17MT
      and EB on the ovary using molecular and histopathological tools. Female rats were
      evaluated after 1, 3 or 7 days following an oral exposure by gavage at a daily
      dose of 600 mg/kg/day for 17MT and 5 mg/kg/day for EB. All animals were found to
      be acyclic after 3 or 7 days of treatment with 17MT and EB. Histopathological
      changes were present in the ovary, uterus, vagina and mammary gland after both
      treatments. Ovarian atrophy known as the long term effect of 17MT and EB was not
      yet detected after 7 days of treatment. But non regressive corpora lutea and
      cystic follicles were identically observed in the ovary of 17MT and EB treated
      females. Both compounds induced a decrease of LH transcripts together with an
      increase of plasma progesterone and prolactin levels. Differences in the profile
      of regulation of the aromatase were noted after 1 and 3 days of treatment in 17MT
      treated animals (upregulated) when compared to EB treated animals
      (downregulated). In summary, we have shown that despite the different nature of
      hormonal activity, EB and 17MT induce very early endocrine perturbation which
      presents several similarities. Our work indicated that the detection of early key
      hormonal markers in short term studies can help to predict the adverse long term
      effects on target tissues.

PMID- 22405604
TI  - [A persistent hypothyroidism].

PMID- 22405605
TI  - Identification of a foreign body--tick (Ixodes)--with confocal laser scan
      microscopy (CLSM) in comparison to histology in a mouse model.

PMID- 22405606
TI  - External beam radiation therapy is safe and effective in treating primary
      pulmonary amyloidosis.
AB  - The aim of the prospective study was to explore the safety and effectiveness of
      external beam radiation therapy (EBRT) in three patients with biopsy proven
      primary pulmonary amyloidosis, including two tracheobronchial amyloidosis
      patients and one primary parenchymal amyloidosis patient. All three patients were
      treated to 24 Gy in 12 fractions utilizing CT simulation and 3-D planning. All
      three patients had significant improvement in clinical symptoms, radiological
      imaging as well as pulmonary function tests. The improvement in the clinical
      symptoms was evident in 2 days. Toxicities related to EBRT were not observed
      during the follow-up range from 42 to 54 months. EBRT to 24 Gy was safe and
      effective in the three patients with primary pulmonary amyloidosis, and resulted
      in rapid relief of pulmonary symptoms.

PMID- 22405607
TI  - Hyponatremia as prognostic factor in small cell lung cancer--a retrospective
      single institution analysis.
AB  - PURPOSE: The aim of this retrospective study is to present data on clinical
      significance of hyponatremia in an unselected contemporary patient population
      with small cell lung cancer (SCLC) with limited disease (LD) and extensive
      disease (ED). PATIENTS AND METHODS: Our electronic database was searched for
      patients with newly diagnosed SCLC from June 2004 to December 2008. 395 cases
      were identified. We collected data on patient characteristics including clinical
      performance status, serum sodium values, serum LDH values, metastatic sites,
      chemotherapy regimens and response, radiotherapy and survival. RESULTS:
      Hyponatremia (sodium <135 mmol/l) was present in 18.9% of all cases. Severe
      hyponatremia (sodium <129 mmol/l) was detected in 8.8%. Hyponatremia was present
      in 58 out of 241 (24%) patients with ED SCLC and 17 of 154 (11%) patients with LD
      SCLC. Hyponatremia was associated with significantly shorter median survival
      (SCLC all patients: 9.0 vs. 13.0 months, p < 0.001, LD SCLC: 9.0 vs. 17.0, p =
      0.050, ED SCLC 9.0 vs. 10.0, p = 0.135). After adjustment for age, gender, LDH
      and performance status hyponatremia was an independent predictor of mortality in
      patients with ED and LD SCLC. CONCLUSION: According to the extensive statistical
      analyses in our comprehensive unselected patient population, hyponatremia seems
      to constitute an independent prognostic factor in patients with SCLC.

PMID- 22405608
TI  - The value of exhaled nitric oxide to identify asthma in smoking patients with
      asthma-like symptoms.
AB  - BACKGROUND: The fraction of nitric oxide in exhaled air (FeNO) is used in asthma
      diagnosis and management. Smoking reduces FeNO and 20-35% of asthmatics are
      smoking. However no guidelines exist on the diagnostic value of FeNO in smokers.
      Therefore we assessed the value of FeNO to diagnose asthma in a population of
      subjects with asthma-like symptoms and different smoking habits. METHODS:
      Measurements of FeNO, lung function, bronchial responsiveness and allergy testing
      were performed in 282 subjects (108 never-, 62 ex- and 112 current smokers) aged
      14-44 years, with symptoms suggestive of asthma. These subjects were a subset of
      subjects reporting respiratory symptoms (n = 686) in a random population sample
      (n = 10,400). RESULTS: A diagnosis of asthma was given to 96 of the 282 subjects.
      Subjects with asthma had higher FeNO levels than subjects with non-specific
      asthma symptoms in all three smoking strata (p < 0.001), with a percentual
      increase of FeNO by 76% in never-, 71% in ex- and 60% in current smokers. The
      area under the ROC-curve was similar in never-, ex- and current smokers (0.72 vs.
      0.74 vs. 0.70). The cut-offs were approximately 30% lower for either 90%
      specificity (22 vs. 31 ppb) or 90% sensitivity (7 vs. 10 ppb) in current vs.
      never-smokers. CONCLUSIONS: FeNO could differentiate asthmatic subjects from non
      asthmatic subjects with asthma-like symptoms equally well in both never- and
      current smokers within a random population sample. The FeNO cut-off levels needed
      in order to achieve high sensitivity or specificity were lower in current
      smokers.

PMID- 22405609
TI  - The requirement for proper storage of nuclear and related decommissioning samples
      to safeguard accuracy of tritium data.
AB  - Large volumes of potentially tritium-contaminated waste materials are generated
      during nuclear decommissioning that require accurate characterisation prior to
      final waste sentencing. The practice of initially determining a radionuclide
      waste fingerprint for materials from an operational area is often used to save
      time and money but tritium cannot be included because of its tendency to be
      chemically mobile. This mobility demands a specific measurement for tritium and
      also poses a challenge in terms of sampling, storage and reliable analysis. This
      study shows that the extent of any tritium redistribution during storage will
      depend on its form or speciation and the physical conditions of storage. Any
      weakly or moderately bound tritium (e.g. adsorbed water, waters of hydration or
      crystallisation) may be variably lost at temperatures over the range 100-300 
      degrees C whereas for more strongly bound tritium (e.g. chemically bound or held
      in mineral lattices) the liberation temperature can be delayed up to 800  degrees
      C. For tritium that is weakly held the emanation behaviour at different
      temperatures becomes particularly important. The degree of (3)H loss and cross
      contamination that can arise after sampling and before analysis can be reduced by
      appropriate storage. Storing samples in vapour tight containers at the point of
      sampling, the use of triple enclosures, segregating high activity samples and
      using a freezer all lead to good analytical practice.

PMID- 22405610
TI  - Heavy metal fate in pilot-scale sludge drying reed beds under various design and
      operation conditions.
AB  - Thirteen pilot-scale sludge drying reed bed (SDRB) units have been constructed
      and operated under various settings. The beds included a cobbles lower layer,
      where perforated PVC aeration tubes were placed, and two gravel layers on top.
      The setup included planted beds with common reeds and control units. Three sludge
      loading rates (SLR) were examined: 30, 60 and 75 kg dm/m(2)/yr. Heavy metal (HM)
      accumulation in the residual sludge layer was negligible or low, and was found to
      increase with sludge layer depth. Plant uptake was low; the belowground biomass
      accumulated significantly more HMs compared to the aboveground biomass. Less than
      16% of the influent HM left the bed through drainage. HM accumulation in the
      gravel layer was the major metal sink in the mass balance. On the whole, the HM
      content of the residual sludge was below the legal limits proposed by the EU for
      land application.

PMID- 22405611
TI  - Evaluation of two new automated chemiluminescent assays (HemosIL(r) AcuStar HIT
      IgG and HemosIL(r) AcuStar HIT-Ab) for the detection of heparin-induced
      antibodies in the diagnosis of heparin-induced thrombocytopenia.
AB  - INTRODUCTION: Recently, two new, fully automated quantitative chemiluminescent
      immunoassays, the HemosIL((r)) AcuStar HIT-IgG (PF4-H), specific for IgG anti
      PF4/H antibodies, and the HemosIL((r)) AcuStar HIT-Ab(PF4-H), detecting IgG, IgM
      and IgA anti-PF4/H antibodies, were introduced into the market. In this study,
      their performance was compared mutually and with the Zymutest HIA IgG and HIA
      IgGAM ELISA. METHODS: Citrated plasmas from 87 patients with clinical suspicion
      of heparin-induced thrombocytopenia (HIT) were analyzed with all four assays and
      with a functional confirmation assay. Apart from the manufacturer's cutoffs,
      optimalized cutoffs were evaluated as well. RESULTS: Sensitivities of all assays
      were 100%. The Acustar HIT-IgG assay showed a higher specificity compared with
      the HIT-Ab assay (85%vs. 73%), using the manufacturer's cutoffs. Specificities of
      all assays, except for the AcuStar HIT-IgG, could be significantly improved when
      altering the cutoff. Titers were significantly higher for the HIT-Ab assay
      compared with the HIT-IgG assay (P = 0.0001). This was also the case for the
      patients with confirmed HIT (P = 0.0495), indicating that the one cutoff (1.0 OD)
      for both Acustar assays, as proposed by the manufacturer, can be adapted for the
      AcuStar Hit-Ab assay resulting in an increased specificity. CONCLUSION:
      Performance characteristics of the Acustar HIT-IgG and HIT-Ab assay are
      comparable to the Zymutest HIA IgG and HIA IgGAM.

PMID- 22405612
TI  - Commentary: The degenerative lumbar spine: a chronic condition in search of a
      definitive solution.

PMID- 22405613
TI  - Commentary: Validity and responsiveness of measures of walking in lumbar spinal
      stenosis--what are we measuring?

PMID- 22405614
TI  - Sacral kyphoplasty for the treatment of painful sacral insufficiency fractures
      and metastases.
AB  - BACKGROUND CONTEXT: Sacral insufficiency fractures and metastases are a source of
      severe intractable pain, with limited therapeutic options. Sacroplasty has
      demonstrable efficacy and safety; sacral kyphoplasty, however, is rarely
      reported. PURPOSE: To evaluate the safety and efficacy of sacral kyphoplasty for
      sacral insufficiency fractures and metastases. STUDY DESIGN: Retrospective, with
      long-term follow-up; rural community-based practice. PATIENT SAMPLE: Patients
      with sacral insufficiency fractures and metastases. OUTCOME MEASURES: Numerical
      pain rating scale, opioid equivalent usage. SELF-REPORT MEASURE: Numerical pain
      rating scale. FUNCTIONAL MEASURE: Opioid equivalent consumption. METHODS:
      Retrospective analysis. RESULTS: Statistically significant improvement in pain;
      overall, an improvement in opioid consumption. CONCLUSIONS: Sacral kyphoplasty
      appears to be a safe and efficacious procedure, comparable to sacroplasty, in the
      treatment of SIFs and sacral metastases.

PMID- 22405615
TI  - Commentary: Electromyographic thresholds for stimulated thoracic pedicle screws
      are influenced by multiple factors.

PMID- 22405616
TI  - Biomechanical analysis of the C2 intralaminar fixation technique using a cross
      link and offset connector for an unstable atlantoaxial joint.
AB  - BACKGROUND CONTEXT: C2 intralaminar screws offer the advantage of avoiding the
      vertebral artery; however, biomechanical studies have demonstrated inferiority of
      C2 intralaminar screw fixation compared with C2 intrapedicular fixation in the
      presence of an odontoid fracture. Addition of a transverse cross-link may improve
      stability afforded by the lamina screws but will require the use of offset
      connectors to complete the construct. PURPOSE: The aims of this project were to
      evaluate whether transverse cross-links can add adequate stability to
      atlantoaxial constructs using C1 lateral mass and C2 intralaminar screw fixation.
      The secondary objective was to determine the biomechanical contribution of the C2
      offset connectors. STUDY DESIGN: In vitro human cadaveric biomechanical study.
      METHODS: Ten cadaveric specimens were obtained and instrumented with C1 lateral
      mass, C2 pedicle, and C2 intralaminar screws. After intact spine testing, each C1
      C2 construct was nondestructively evaluated under axial rotation (AR), flexion
      extension (FE), and lateral bending (LB). Intralaminar fixation was tested with
      and without offset connectors, which allowed for cross-link addition to the
      construct. After normal state evaluation, the odontoid was resected and analyses
      were repeated. RESULTS: Postreconstruction range of motion in AR, FE, and LB
      showed no significant differences between the four fixation constructs in the
      stable specimens. Transpedicular fixation at C2 proved superior to intralaminar
      techniques without a cross-link in AR and LB after destabilization with an
      odontoidectomy. The addition of a cross-link to the intralaminar construct
      improved segmental AR and LB stability to the level afforded by the
      transpedicular fixation. Offset connectors appeared to marginally weaken the
      intralaminar fixation, but the findings were not significant. CONCLUSIONS:
      Coupled with an offset connector and a cross-link, C2 intralaminar screws offer
      similar segmental stability to intrapedicular fixation in the presence of an
      unstable dens fracture. Lateral offset connectors at C2 do not significantly
      compromise stability of C1 lateral mass-C2 intralaminar fixation.

PMID- 22405617
TI  - The biomechanical stability of a novel spacer with integrated plate in contiguous
      two-level and three-level ACDF models: an in vitro cadaveric study.
AB  - BACKGROUND CONTEXT: Anterior cervical plating increases stability and hence
      improves fusion rates to treat cervical spine pathologies, which are often
      symptomatic at multiple levels. However, plating is not without complications,
      such as dysphagia, injury to neural elements, and plate breakage. The
      biomechanics of a spacer with integrated plate system combined with posterior
      instrumentation (PI), in two-level and three-level surgical models, has not yet
      been investigated. PURPOSE: The purpose of the study was to biomechanically
      evaluate the multidirectional rigidity of spacer with integrated plate (SIP) at
      multiple levels as comparable to traditional spacers and plating. STUDY DESIGN:
      An in vitro cervical cadaveric model. METHODS: Eight fresh human cervical (C2-C7)
      cadaver spines were tested under pure moments of +/-1.5 Nm on spine simulator
      test frame. Each spine was tested in intact condition, with only anterior
      fixation and with both anterior and PI. Range of motion (ROM) was measured using
      Optotrak Certus (NDI, Inc., Waterloo, Ontario, Canada) motion analysis system in
      flexion-extension (FE), lateral bending (LB), and axial rotation (AR) at the
      instrumented levels (C3-C6). Repeated-measures analysis of variance was used for
      statistical analysis. RESULTS: All the surgical constructs showed significant
      reduction in motion compared with intact condition. In two-level fusion, SIP (C4
      C6) construct significantly reduced ROM by 66.5%, 65.4%, and 60.3% when compared
      with intact in FE, LB, and AR, respectively. In three-level fusion, SIP (C3-C6)
      construct significantly reduced ROM by 65.8%, 66%, and 49.6% when compared with
      intact in FE, LB, and AR, respectively. Posterior instrumentation showed
      significant stability only in three-level fusion when compared with their
      respective anterior constructs. In both two-level and three-level fusion, SIP
      showed comparable stability to traditional spacer and plate constructs in all
      loading modes. CONCLUSIONS: The anatomically profiled spacer with integrated
      plate allows treatment of cervical disorders with fewer steps and less impact to
      cervical structures. In this biomechanical study, spacer with integrated plate
      construct showed comparable stability to traditional spacer and plate for two
      level and three-level fusion. Posterior instrumentation showed significant effect
      only in three-level fusion. Clinical data are required for further validation of
      using spacer with integrated plate at multiple levels.

PMID- 22405618
TI  - Fear avoidance beliefs and low back pain: "practical reviews" from expert panel
      discussions versus comprehensive systematic reviews.

PMID- 22405620
TI  - Intradiscal injection therapy for degenerative chronic discogenic low back pain
      with end plate Modic changes.

PMID- 22405622
TI  - The negative effects of MST and combat injuries among female soldiers: a major
      concern.

PMID- 22405623
TI  - Mutation analysis of the NRXN1 gene in a Chinese autism cohort.
AB  - Autism is a brain developmental disorder characterized by impaired social
      interaction and communication, as well as restricted and repetitive behaviors.
      The neurexin-1(NRXN1) gene mapped on chromosome 2p16.3 encodes neurexin, a cell
      adhesion molecule and receptor in the vertebrate nervous system. Rare de novo
      alterations and copy number variations (CNVs) suggested neurexin-1 as a candidate
      gene for the pathogenesis of autism, but data on the gene mutation of neurexin-1
      in Chinese Han population with autism are limited. By direct sequencing, we
      analyzed the entire coding regions and associated splice junctions of neurexin-1
      in 313 Chinese autism patients. For exons in which non-synonymous variants were
      identified, sequencing was performed in 500 healthy controls. We identified 22
      variants in the neurexin-1 coding regions, including 7 missense variants, 3
      deletions, and 12 synonymous mutations. Among them, 3 missense and 3 synonymous
      variants were not reported in the dbSNP database and absent in 500 control
      subjects; whereas 4 missense variants, 3 deletions and 3 synonymous mutations
      were not reported in the dbSNP database but were identified in the control
      subjects. However, there is no significant association of these mutations with
      autism risk. Interestingly, there was a statistically significant association of
      neurexin-1 SNP P300P (rs2303298) with risk of autism (26.2% vs. 13.8%; chi(2) =
      22.487; p = 3.45E-006; OR = 2.152 (1.559-2.970)). Our data suggest a possible
      association of neurexin-1 with autism risk in Chinese Han population, warranting
      further large-scale study on this gene.

PMID- 22405624
TI  - Viral infections and atopy in Brazil.

PMID- 22405626
TI  - Cis-acting element (SL1) of Potato virus X controls viral movement by interacting
      with the NbMPB2Cb and viral proteins.
AB  - A number of candidate tobacco proteins that bind to cis-acting elements (SL1
      RNAs) of Potato virus X (PVX) have been identified in previous studies. We
      further characterized TMV-MP30 binding protein 2C (MPB2C) homologous protein. We
      isolated NbMPB2Cb from Nicotiana benthamiana and confirmed the interaction of
      NbMPB2Cb with SL1 RNAs in vitro. The mRNA level of NbMPB2Cb was increased upon
      infection by PVX and Tobacco mosaic virus. The movement of PVX was reduced by
      overexpression of NbMPB2Cb and increased by silenced of NbMPB2Cb. In contrast,
      PVX RNA accumulation was not significantly altered in protoplasts. Protein
      protein interaction assays showed that NbMPB2Cb interacts with PVX movement
      associated proteins. PVX infection altered the subcellular localization of
      NbMPB2Cb from microtubules to endoplasmic reticulum. These data suggest that the
      NbMPB2Cb negatively affects PVX movement by interacting with SL1 RNAs and
      movement-associated proteins of PVX and by re-localizing in response to PVX
      infection.

PMID- 22405627
TI  - Comparison of the convergent receptor utilization of a retargeted feline leukemia
      virus envelope with a naturally-occurring porcine endogenous retrovirus A.
AB  - In vitro screening of randomized FeLV Envelope libraries identified the CP
      isolate, which enters cells through HuPAR-1, one of two human receptors utilized
      by porcine endogenous retrovirus-A (PERV-A), a distantly related gammaretrovirus.
      The CP and PERV-A Envs however, share little amino acid homology. Their receptor
      utilization was examined to define the common receptor usage of these disparate
      viral Envs. We demonstrate that the receptor usage of CP extends to HuPAR-2 but
      not to the porcine receptor PoPAR, the cognate receptor for PERV-A. Reciprocal
      interference between virus expressing CP and PERV-A Envs was observed on human
      cells. Amino acid residues localized to within the putative second extracellular
      loop (ECL-2) of PAR-1 and PAR-2 are found to be critical for CP envelope
      function. Through a panel of receptor chimeras and point mutations, this area was
      also found to be responsible for the differential usage of the PoPAR receptor
      between CP and PERV-A.

PMID- 22405628
TI  - Evidence of an oncogenic gammaherpesvirus in domestic dogs.
AB  - In humans, chronic infection with the gammaherpesvirus Epstein-Barr virus is
      usually asymptomatic; however some infected individuals develop hematological and
      epithelial malignancies. The exact role of EBV in lymphomagenesis is poorly
      understood partly because of the lack of clinically relevant animal models. Here
      we report the detection of serological responses against EBV capsid antigens in
      healthy dogs and dogs with spontaneous lymphoma and that dogs with the highest
      antibody titers have B cell lymphoma. Moreover, we demonstrate the presence of
      EBV-like viral DNA and RNA sequences and Latent Membrane Protein-1 in malignant
      lymph nodes of dogs with lymphoma. Finally, electron microscopy of canine
      malignant B cells revealed the presence of classic herpesvirus particles. These
      findings suggest that dogs can be naturally infected with an EBV-like
      gammaherpesvirus that may contribute to lymphomagenesis and that dogs might
      represent a spontaneous model to investigate environmental and genetic factors
      that influence gammaherpesvirus-associated lymphomagenesis in humans.

PMID- 22405629
TI  - Prediction of haematoma expansion with the CTA spot sign: a useful biomarker?

PMID- 22405631
TI  - The next frontier of clinical trials: personalized medicine for devices.

PMID- 22405630
TI  - Prediction of haematoma growth and outcome in patients with intracerebral
      haemorrhage using the CT-angiography spot sign (PREDICT): a prospective
      observational study.
AB  - BACKGROUND: In patients with intracerebral haemorrhage (ICH), early haemorrhage
      expansion affects clinical outcome. Haemostatic treatment reduces haematoma
      expansion, but fails to improve clinical outcomes in many patients. Proper
      selection of patients at high risk for haematoma expansion seems crucial to
      improve outcomes. In this study, we aimed to prospectively validate the CT
      angiography (CTA) spot sign for prediction of haematoma expansion. METHODS:
      PREDICT (predicting haematoma growth and outcome in intracerebral haemorrhage
      using contrast bolus CT) was a multicentre prospective observational cohort
      study. We recruited patients aged 18 years or older, with ICH smaller than 100
      mL, and presenting at less than 6 h from symptom onset. Using two independent
      core laboratories, one neuroradiologist determined CTA spot-sign status, whereas
      another neurologist masked for clinical outcomes and imaging measured haematoma
      volumes by computerised planimetry. The primary outcome was haematoma expansion
      defined as absolute growth greater than 6 mL or a relative growth of more than
      33% from initial CT to follow-up CT. We reported data using standard descriptive
      statistics stratified by the CTA spot sign. Mortality was assessed with Kaplan
      Meier survival analysis. FINDINGS: We enrolled 268 patients. Median time from
      symptom onset to baseline CT was 135 min (range 22-470), and time from onset to
      CTA was 159 min (32-475). 81 (30%) patients were spot-sign positive. The primary
      analysis included 228 patients, who had a follow-up CT before surgery or death.
      Median baseline ICH volume was 19.9 mL (1.5-80.9) in spot-sign-positive patients
      versus 10.0 mL (0.1-102.7) in spot-sign negative patients (p<0.001). Median ICH
      expansion was 8.6 mL (-9.3 to 121.7) for spot-sign positive patients and 0.4 mL (
      11.7 to 98.3) for spot-negative patients (p<0.001). In those with haematoma
      expansion, the positive predictive value for the spot sign was61% (95% CI 47-73)
      for the positive predictive value and 78% (71-84) for the negative predictive
      value, with 51% (39-63) sensitivity and 85% (78-90) specificity[corrected].
      Median 3-month modified Rankin Scale (mRS) was 5 in CTA spot-sign-positive
      patients, and 3 in spot-sign-negative patients (p<0.001). Mortality at 3 months
      was 43.4% (23 of 53) in CTA spot-sign positive versus 19.6% (31 of 158) in CTA
      spot-sign-negative patients (HR 2.4, 95% CI 1.4-4.0, p=0.002). INTERPRETATION:
      These findings confirm previous single-centre studies showing that the CTA spot
      sign is a predictor of haematoma expansion. The spot sign is recommended as an
      entry criterion for future trials of haemostatic therapy in patients with acute
      ICH. FUNDING: Canadian Stroke Consortium and NovoNordisk Canada.

PMID- 22405632
TI  - Targeted left ventricular lead placement to guide cardiac resynchronization
      therapy: the TARGET study: a randomized, controlled trial.
AB  - OBJECTIVES: This study sought to assess the impact of targeted left ventricular
      (LV) lead placement on outcomes of cardiac resynchronization therapy (CRT).
      BACKGROUND: Placement of the LV lead to the latest sites of contraction and away
      from the scar confers the best response to CRT. We conducted a randomized,
      controlled trial to compare a targeted approach to LV lead placement with usual
      care. METHODS: A total of 220 patients scheduled for CRT underwent baseline
      echocardiographic speckle-tracking 2-dimensional radial strain imaging and were
      then randomized 1:1 into 2 groups. In group 1 (TARGET [Targeted Left Ventricular
      Lead Placement to Guide Cardiac Resynchronization Therapy]), the LV lead was
      positioned at the latest site of peak contraction with an amplitude of >10% to
      signify freedom from scar. In group 2 (control) patients underwent standard
      unguided CRT. Patients were classified by the relationship of the LV lead to the
      optimal site as concordant (at optimal site), adjacent (within 1 segment), or
      remote (>=2 segments away). The primary endpoint was a >=15% reduction in LV end
      systolic volume at 6 months. Secondary endpoints were clinical response (>=1
      improvement in New York Heart Association functional class), all-cause mortality,
      and combined all-cause mortality and heart failure-related hospitalization.
      RESULTS: The groups were balanced at randomization. In the TARGET group, there
      was a greater proportion of responders at 6 months (70% vs. 55%, p = 0.031),
      giving an absolute difference in the primary endpoint of 15% (95% confidence
      interval: 2% to 28%). Compared with controls, TARGET patients had a higher
      clinical response (83% vs. 65%, p = 0.003) and lower rates of the combined
      endpoint (log-rank test, p = 0.031). CONCLUSIONS: Compared with standard CRT
      treatment, the use of speckle-tracking echocardiography to the target LV lead
      placement yields significantly improved response and clinical status and lower
      rates of combined death and heart failure-related hospitalization. (Targeted Left
      Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy [TARGET]
      study); ISRCTN19717943).

PMID- 22405633
TI  - Abnormality of glycometabolism related factors in non-psychotic offspring of
      schizophrenic patients.
AB  - Schizophrenic patients appear to have higher rates of abnormality of
      glycometabolism. It has been suggested that these could be secondary to the use
      of antipsychotics. However, findings indicate that abnormal glucose metabolism
      may be potentially involved in the pathogenesis of schizophrenia. The present
      study examined the fasting plasma levels of glycometabolism related factors in
      healthy offspring of schizophrenic patients. Our objective was to test the
      hypothesis that abnormal glucose metabolism might be potentially involved in the
      pathogenesis of schizophrenia. Thirty-two healthy offspring of schizophrenic
      inpatients who met DSM-IV criteria for schizophrenia and 37 comparison subjects
      were recruited. Fasting plasma levels of glucose, insulin, insulin-like growth
      factor 1 (IGF-1), growth hormone (GH), leptin and cortisol were tested for all
      subjects. Compared with controls, offspring of schizophrenic patients had
      significantly higher mean plasma insulin and insulin resistance, and lower mean
      plasma IGF-1 level. Meanwhile, the mean fasting plasma levels of glucose, GH,
      leptin and cortisol did not differ significantly between offspring of
      schizophrenic patients and healthy comparison subjects. Offspring of
      schizophrenic patients showed significant differences from comparison subjects in
      glycometabolism related factors. Abnormal glucose metabolism might be potentially
      involved in the pathogenesis of schizophrenia.

PMID- 22405634
TI  - Utility of the MMPI-2-RF in detecting non-credible somatic complaints.
AB  - We examined the utility of the Minnesota Multiphasic Personality Inventory-2
      Restructured Form (MMPI-2-RF) validity scales (infrequent responses (F-r),
      infrequent psychopathology responses (Fp-r), infrequent somatic responses (Fs),
      symptom validity (FBS-r), and response bias (RBS)) in differentiating individuals
      who were asked to feign physical health problems from a group of somatoform
      disorder patients and genuine medical patients with no history of mental health
      problems. A large group of undergraduate students were instructed to feign
      physical health problems as if they were participating in a disability evaluation
      for a work-related injury. Comparison groups were drawn from archival databases
      and consisted of non-litigating medical patients or individuals carefully
      diagnosed with somatoform disorder. The Fs and Fp-r scales were associated with
      the best differentiation between the three groups; the Fs scale was the most
      sensitive to somatic malingering, whereas the Fp-r scale was the most specific.
      Both scales were associated with high likelihood ratios in differentiating the
      somatic malingering group from the somatoform and medical illness groups.
      Although the FBS-r scale was overall the most sensitive in differentiating non
      credible somatic complaints from genuine medical illness, it could not
      differentiate well between the somatic malingering and somatoform patient
      conditions. The MMPI-2-RF appears to have considerable promise in detecting
      individuals who feign physical health problems. Not surprisingly, differentiating
      somatic malingering from somatoform disorder with the MMPI-2-RF was less accurate
      than differentiating somatic malingering from bona-fide medical patients.

PMID- 22405635
TI  - An association between affective lability and executive functioning in bipolar
      disorder.
AB  - Studies suggest altered affect regulation manifested by affective lability in
      manic/mixed and euthymic states in patients with bipolar disorder (BD). Altered
      affect regulation may arise from disturbances in interactions between the
      cognitive and the emotional brain networks. However, the relationship between
      affective lability and executive function has not previously been studied. Our
      aim was to investigate affective lability, as measured with the Affective
      Lability Scale (ALS) in patients with BD (N=32) compared to healthy controls (HC)
      (N=60), and its relationship to executive functioning. We found significantly
      higher ALS scores in the BD than in the HC group, indicating a higher degree of
      affective lability in patients with BD. Sub-sample analysis revealed a
      significant positive relationship between affective lability and semantic set
      shifting abilities in BD only. These findings suggest that higher levels of
      affective lability compared with controls are a trait as well as state dependent
      in BD, and that disturbed affective lability may arise from an aberrant
      interaction between cognitive and emotional brain networks.

PMID- 22405636
TI  - Negative life events and mental health of Chinese medical students: the effect of
      resilience, personality and social support.
AB  - The present study was conducted on a large sample of Chinese medical students to
      test the moderating effect of resilience between negative life events and mental
      health problems, and investigate the factors that affect the mental health
      problems of the students. The Adolescent Self-Rating Life Events Check List,
      Eysenck Adult Personality Questionnaire-Revised, Social Support Rating Scale,
      Connor-Davidson Resilience Scale, and Symptom Check List were adopted for a
      survey with 1,998 Chinese medical students as respondents. Mental health problems
      had a positive correlation with negative life events and neuroticism. On the
      other hand, mental health problems had a negative correlation with social
      support, extraversion, and resilience. Regression analysis showed that resilience
      moderated negative life events and mental health problems. Promoting resilience
      may be helpful for the adjustment of college students.

PMID- 22405637
TI  - Incidence patterns of small bowel cancer in a population-based study in Sweden:
      increase in duodenal adenocarcinoma.
AB  - BACKGROUND: Increasing incidences of malignant small bowel tumours have been
      reported, but data from European populations are limited. This study aimed to
      clarify the incidence patterns of malignant small bowel tumours in Sweden.
      METHODS: Patients with a first and primary malignant small bowel tumour were
      identified from the Swedish Cancer Register during the study period 1960-2009.
      Sex-specific and age-standardised incidence rates of these tumours were
      calculated by their anatomical location and histological type in different time
      periods. Figures were plotted to show the proportions and incidence rates over
      time, and joinpoint loglinear regression models were estimated to assess any time
      trends. RESULTS: A total of 6604 patients with malignant small bowel tumours were
      identified. The age-standardised incidence of all malignant small bowel tumours
      increased from 14.2 to 19.7 per 1,000,000 person-years during the study period.
      The incidence of duodenal cancer increased more than 3-fold (from 1.6 to 5.4 per
      1,000,000 person-years), which was mainly expained by a dramatical rising trend
      of adenocarcinoma of the duodenum (from 0.7 to 4.2 per 1,000,000 person-years).
      Malignant tumours of small bowel with unspecified anatomical locations showed a
      slight increase (from 7.0 to 7.9 per 1,000,000). The incidence of small bowel
      tumours in other locations or of other histological types was more stable.
      CONCLUSIONS: The incidence of small bowel malignancies has increased during the
      period 1960-2009. Among the specific types of small bowel cancer, a particularly
      rapid increase was found for duodenal adenocarcinoma.

PMID- 22405638
TI  - Uncertainties in 63Ni and 55Fe determinations using liquid scintillation counting
      methods.
AB  - The implementation of (63)Ni and (55)Fe determination methods in an environmental
      laboratory implies their validation. In this process, the uncertainties related
      to these methods should be analysed. In this work, the expression of the
      uncertainty of the results obtained using separation methods followed by liquid
      scintillation counting is presented. This analysis includes the consideration of
      uncertainties coming from the different alternatives which these methods use as
      well as those which are specific to the individual laboratory and the competency
      of its operators in applying the standard ORISE (Oak Ridge Institute for Science
      and Education) methods.

PMID- 22405639
TI  - Performance analysis of gamma ray spectrometric parameters on digital signal and
      analog signal processing based MCA systems using NaI(Tl) detector.
AB  - Accurate and speedy estimations of ppm range uranium and thorium in the
      geological and rock samples are most useful towards ongoing uranium
      investigations and identification of favorable radioactive zones in the
      exploration field areas. In this study with the existing 5 in. * 4 in. NaI(Tl)
      detector setup, prevailing background and time constraints, an enhanced
      geometrical setup has been worked out to improve the minimum detection limits for
      primordial radioelements K(40), U(238) and Th(232). This geometrical setup has
      been integrated with the newly introduced, digital signal processing based MCA
      system for the routine spectrometric analysis of low concentration rock samples.
      Stability performance, during the long counting hours, for digital signal
      processing MCA system and its predecessor NIM bin based MCA system has been
      monitored, using the concept of statistical process control. Monitored results,
      over a time span of few months, have been quantified in terms of spectrometer's
      parameters such as Compton striping constants and Channel sensitivities, used for
      evaluating primordial radio element concentrations (K(40), U(238) and Th(232)) in
      geological samples. Results indicate stable dMCA performance, with a tendency of
      higher relative variance, about mean, particularly for Compton stripping
      constants.

PMID- 22405640
TI  - Evaluation of trace elemental composition of aerosols in the atmosphere of
      Rawalpindi and Islamabad using radio analytical methods.
AB  - Geological and anthropogenic contributions to air pollution were monitored by
      analyzing aerosol particulates present in the atmosphere of Rawalpindi and
      Islamabad, Pakistan, using instrumental neutron activation for trace elemental
      analysis. A scanning electron microscope was used to study particulate size
      distribution and morphology. Twenty two elements were analyzed and their likely
      sources were identified. It was found that 69% of the suspended particulate
      matter in the atmosphere of Islamabad, and 52% in Rawalpindi, were of a diameter
      less than 3 MUm. The presence of Yb, Cs, Sc, Rb, Co, Eu, La, Ba, Zn and Hf
      indicates that a major portion of the trace elements in the aerosol particulates
      was due to the geological nature of the land, while Sc was considered to be
      arising from coal burning. The presence of Cr, Fe, Ce, Pb and Cd was attributed
      to anthropogenic activities at Rawalpindi and Islamabad. Unusually high
      concentrations of Mo and Nb were found in the atmosphere of Islamabad, based on
      soil derived aerosols.

PMID- 22405641
TI  - Characterization of photon-emitting wide area reference sources.
AB  - A procedure has been developed to calibrate photon-emitting wide area reference
      sources in terms of activity, surface emission rate and uniformity considering
      the requirements introduced by the recent revision of ISO standard 8769. The
      method makes use of a large volume NaI detector with a cross table scanning
      system, a radiography system and it applies Monte Carlo techniques to assess the
      surface emission rate. The method was successfully applied to sources of (241)Am,
      (57)Co, (137)Cs and (60)Co. In addition, problems with definitions and the
      practical use of standard ISO 8769:2010 are highlighted.

PMID- 22405642
TI  - On the long-term stability of calibration standards in different matrices.
AB  - In order to assure Quality Control in accordance with ISO/IEC 17025, it was
      important, from metrological point of view, to examine the long-term stability of
      calibration standards previously prepared. Comprehensive reconsideration on
      efficiency curves with respect to the ageing of calibration standards is
      presented in this paper. The calibration standards were re-used after a period of
      5 years and analysis of the results showed discrepancies in efficiency values.

PMID- 22405643
TI  - Preparation of [In-111]-labeled-DTPA-bombesin conjugates at high specific
      activity and stability: evaluation of labeling parameters and potential
      stabilizers.
AB  - The aim of the present work was to obtain stabilized high specific activity (HSA)
      (111)In-labeled bombesin conjugates for preclinical evaluations. Parameters
      influencing the kinetics of labeling were investigated and the effect of
      stabilizers on HSA radiopeptides stability at room temperature were
      systematically categorized applying chromatography techniques. A SA of 174
      GBq/MUmol was achieved with high radiochemical purity, but the labeled compounds
      exhibited low stability. The addition of stabilizers avoided their radiolysis and
      significantly increased their stability.

PMID- 22405644
TI  - Oral glycopyrrolate as second-line treatment for primary pediatric hyperhidrosis.
AB  - BACKGROUND: Primary focal hyperhidrosis not uncommonly begins during the first
      two decades of life, and can have a profound effect on quality of life. Few
      treatment options have been studied in children. OBJECTIVE: We sought to evaluate
      the response to oral glycopyrrolate in pediatric patients. METHODS: Records of
      pediatric patients with hyperhidrosis seen at a pediatric hospital in a 10-year
      period were reviewed retrospectively and, if possible, parents and patients were
      also interviewed. The efficacy and adverse effects of oral glycopyrrolate were
      assessed. RESULTS: In all, 31 children took at least one dose of oral
      glycopyrrolate. All had daily hyperhidrosis that affected their quality of life
      and were resistant or intolerant of aluminum salts. The mean age of hyperhidrosis
      onset was 10.3 years, and mean age of initiation of glycopyrrolate was 14.8
      years. At a mean dosage of 2 mg daily, 90% of patients experienced improvement,
      which was major in 71% of responders. Improvement occurred within hours of
      administration and disappeared within a day of discontinuation. Duration of
      treatment averaged 2.1 years (range to 10 years). Side effects were noted by 29%
      of children, most commonly dry mouth (26%) and eyes (10%), and were dose-related.
      One patient developed blurred vision, which resolved with dosing below 5 mg/d;
      one patient experienced palpitations and discontinued the medication.
      LIMITATIONS: This was a retrospective analysis of a limited number of pediatric
      patients. CONCLUSION: Oral glycopyrrolate is a cost-effective, painless second
      line therapy for children and adolescents with primary focal hyperhidrosis that
      impacts their quality of life.

PMID- 22405645
TI  - A review of Parry-Romberg syndrome.
AB  - Parry-Romberg syndrome, also known as progressive hemifacial atrophy, is a rare
      disorder characterized by unilateral facial atrophy affecting the skin,
      subcutaneous tissue, muscles, and sometimes extending to the osteocartilaginous
      structures. It has been associated with various systemic manifestations,
      particularly neurologic, ophthalmologic and maxillofacial. In this article, we
      review Parry-Romberg syndrome with its associated findings (neurologic,
      ophthalmologic, cardiac, rheumatologic, endocrinologic, infectious, orthodontic
      and maxillofacial, and autoimmune), underlying cause, differential diagnoses (en
      coup de sabre, scleroderma, and Rasmussen encephalitis), and therapeutic options.

PMID- 22405646
TI  - Synthesis and biological evaluation of novel bifendate derivatives bearing 6,7
      dihydro-dibenzo[c,e]azepine scaffold as potent P-glycoprotein inhibitors.
AB  - Overexpression of P-glycoprotein (P-gp) is one of the major problems in
      successful treatment of cancers. To find new P-gp inhibitors, a series of
      bifendate (DDB) derivatives bearing dibenzo[c,e]azepine scaffold were synthesized
      and evaluated. Compound 4i more potently reversed P-gp-mediated multidrug
      resistance (MDR) than DDB and verapamil (VRP) by blocking P-gp mediated drug
      efflux function and increasing drug accumulation in K562/A02 MDR cells, and
      persisted longer chemo-sensitizing effect (>24 h) than VRP (<6 h). Interestingly,
      unlike VRP, 4i showed no stimulation on the P-gp ATPase activity, suggesting it
      is not a substrate of P-gp. Given the low intrinsic cytotoxicity of 4i in vitro,
      it may represent a promising lead for developing therapeutics targeting P-gp
      mediated MDR in combinational cancer chemotherapy.

PMID- 22405647
TI  - Novel isoxazole polycyclic aromatic hydrocarbons as DNA-intercalating agents.
AB  - The third generation of isoxazole polycyclic aromatic hydrocarbons, acting as DNA
      intercalator agents and possessing the binding constants in the range 10(4)-10(5)
      M(-1), in order to easily diffuse targeting remotely implanted tumors, has been
      synthesized in good yields according to the 1,3-dipolar cycloaddition
      methodology. The structure of the obtained cycloadducts has been determined by
      NOE experiments and supported by computational studies at PM3 level. All the
      obtained compounds have been tested for their in vitro cytotoxic activity and the
      most potent of them, (3RS,5SR)-2-benzyl-N,N-dimethyl-3-(pyren-1-yl)isoxazolidine
      5-carboxamide (7d), showed an IC(50) of 4 MUM upon the human lung cancer (A-549)
      cells. Moreover, compound 7d showed binding constant for the intercalation with
      calf thymus DNA, poly-d(AT)(2) and poly-d(GC)(2) of 1.7 * 10(5) M(-1), 1.6 *
      10(5) M(-1) and 0.3 * 10(5) M(-1), respectively. Biological and docking studies
      showed that, in vitro, these compounds complex by intercalation between base
      pairs, approaching the DNA from its minor groove with a preference for the AT
      nucleobases pairs.

PMID- 22405648
TI  - Design and synthesis of novel 5-phenyl-N-piperidine ethanone containing 4,5
      dihydropyrazole derivatives as potential antitumor agents.
AB  - A series of novel 5-phenyl-N-piperidine ethanone-4,5-dihydropyrazole derivatives
      as potential telomerase inhibitors were synthesized. The bioassays demonstrated
      that compounds 4d, 4f, 7a and 7b occupied high antiproliferative activities
      against SGC-7901, MGC-803 and Bcap-37 cell lines. By a modified TRAP assay, some
      titled compounds were tested against telomerase, and compound 7b showed the most
      potent inhibitory activity with IC(50) value at 2.00 +/- 0.40 MUM. The active
      compound 4d was also docked into the telomerase TERT active site to determine the
      probable binding model. The results indicated that conserved residues Lys189,
      Asp254 and Gln308 were important for ligand binding via hydrogen bond
      interactions.

PMID- 22405649
TI  - Growth inhibition of Mycobacterium smegmatis by prodrugs of deoxyxylulose
      phosphate reducto-isomerase inhibitors, promising anti-mycobacterial agents.
AB  - Since Mycobacterium tuberculosis sets up several multiple anti-tuberculosis drug
      resistance mechanisms, development of new drugs with innovative target is urgent.
      The methylerythritol phosphate pathway (MEP) involved in the biosynthesis of
      essential metabolites for the survival of mycobacteria, represents such a target.
      Fosmidomycin 1a and FR900098 1b, two inhibitors of DXR, do not affect the
      viability of M. tuberculosis cells, due to a lack of uptake. To overcome the
      absence of the mycobacterial cell wall crossing of these compounds, we
      synthesized and tested the inhibition potency of acyloxymethyl phosphonate esters
      as prodrugs of fosmidomycin 1a, FR900098 1b and their analogs 2a and 2b on
      Mycobacterium smegmatis. Only the prodrugs 4b-6b inhibit the bacterial growth and
      could be effective anti-mycobacterial agents.

PMID- 22405650
TI  - Inheritance of silent rDNA chromatin is mediated by PARP1 via noncoding RNA.
AB  - Faithful propagation of specific chromatin states requires re-establishment of
      epigenetic marks after every cell division. How the original epigenetic signature
      is inherited after disruption during DNA replication is still poorly understood.
      Here, we show that the poly(ADP-ribose)-polymerase-1 (PARP1/ARTD1) is implicated
      in the maintenance of silent rDNA chromatin during cell division. We demonstrate
      that PARP1 associates with TIP5, a subunit of the NoRC complex, via the noncoding
      pRNA and binds to silent rRNA genes after their replication in mid-late S phase.
      PARP1 represses rRNA transcription and is implicated in the formation of silent
      rDNA chromatin. Silent rDNA chromatin is a specific substrate for ADP
      ribosylation and the enzymatic activity of PARP1 is necessary to establish rDNA
      silencing. The data unravel a function of PARP1 and ADP-ribosylation that serves
      to allow for the inheritance of silent chromatin structures, shedding light on
      how epigenetic marks are transmitted during each cell cycle.

PMID- 22405653
TI  - Phenotypic flexibility in basal metabolic rate is associated with rainfall
      variability among populations of rufous-collared sparrow.
AB  - Phenotypic flexibility in metabolic rates allows organisms to reversibly adjust
      their energy flow to meet challenges imposed by a variable environment. In turn,
      the food habits hypothesis (FHH) predicts that species or populations adjust
      their basal metabolic rate (BMR) according to the diet attributes such as food
      abundance or predictability. Desert ecosystems represent a temporally
      heterogeneous environment because of low rain pulse predictability, which is also
      associated with temporal variation in food resources. In the present study, we
      investigated the relationship between the magnitude of BMR flexibility in
      response to dietary acclimation and the inter-annual rainfall variability in
      three populations of rufous-collared sparrows. Specifically we addressed the
      question of whether birds from a desert environment are more flexible in BMR than
      those from non-desert habitats. We found a positive trend between BMR flexibility
      and the inter-annual rainfall variability. In fact, dietary treatments had a
      significant effect only in desert birds, a result that also supported the FHH.
      Our study confirms the existence of phenotypic variation in response to
      environmental conditions among populations, and also highlights the importance of
      considering the circumstances in which phenotypic flexibility evolves and the
      specific environmental cues that induce their expression.

PMID- 22405652
TI  - Mechanism of translesion transcription by RNA polymerase II and its role in
      cellular resistance to DNA damage.
AB  - UV-induced cyclobutane pyrimidine dimers (CPDs) in the template DNA strand stall
      transcription elongation by RNA polymerase II (Pol II). If the nucleotide
      excision repair machinery does not promptly remove the CPDs, stalled Pol II
      creates a roadblock for DNA replication and subsequent rounds of transcription.
      Here we present evidence that Pol II has an intrinsic capacity for translesion
      synthesis (TLS) that enables bypass of the CPD with or without repair.
      Translesion synthesis depends on the trigger loop and bridge helix, the two
      flexible regions of the Pol II subunit Rpb1 that participate in substrate
      binding, catalysis, and translocation. Substitutions in Rpb1 that promote lesion
      bypass in vitro increase UV resistance in vivo, and substitutions that inhibit
      lesion bypass decrease cell survival after UV irradiation. Thus, translesion
      transcription becomes essential for cell survival upon accumulation of the
      unrepaired CPD lesions in genomic DNA.

PMID- 22405651
TI  - The glomuvenous malformation protein Glomulin binds Rbx1 and regulates cullin
      RING ligase-mediated turnover of Fbw7.
AB  - Fbw7, a substrate receptor for Cul1-RING-ligase (CRL1), facilitates the
      ubiquitination and degradation of several proteins, including Cyclin E and c-Myc.
      In spite of much effort, the mechanisms underlying Fbw7 regulation are mostly
      unknown. Here, we show that Glomulin (Glmn), a protein found mutated in the
      vascular disorder glomuvenous malformation (GVM), binds directly to the RING
      domain of Rbx1 and inhibits its E3 ubiquitin ligase activity. Loss of Glmn in a
      variety of cells, tissues, and GVM lesions results in decreased levels of Fbw7
      and increased levels of Cyclin E and c-Myc. The increased turnover of Fbw7 is
      dependent on CRL and proteasome activity, indicating that Glmn modulates the E3
      activity of CRL1(Fbw7). These data reveal an unexpected functional connection
      between Glmn and Rbx1 and demonstrate that defective regulation of Fbw7 levels
      contributes to GVM.

PMID- 22405654
TI  - Duodenal involvement in multiple myeloma.

PMID- 22405655
TI  - Schizophrenia literacy: the effect of direct experience with the illness.
AB  - The present study examined the idea that those who have had direct experience
      with schizophrenia demonstrate better mental health literacy with regards to the
      condition compared to those with no experience. A convenience sample of 207 lay
      respondents (aged 17-73 years) completed a questionnaire that examined knowledge
      of schizophrenia symptoms, the nature of people with schizophrenia, causes,
      awareness of related disorders and spectrum/schizotypy theories, stereotypical
      attitudes about schizophrenic patients, attitudes towards social contact with
      people with schizophrenia, and whether the respondent or anyone they knew had
      ever been diagnosed with schizophrenia. There were few differences as a function
      of contact, but those with direct experience were indeed found to be more
      comfortable about various interactions with a person with schizophrenia. This
      study provides modest evidence for the contact hypothesis. Suggestions for
      increasing mental health literacy with respect to schizophrenia are considered.

PMID- 22405657
TI  - Divided full-thickness skin graft for closure of circular and oval scalp defects.

PMID- 22405656
TI  - Inflammatory markers in antipsychotic-naive patients with nonaffective psychosis
      and deficit vs. nondeficit features.
AB  - Newly diagnosed, antipsychotic-naive patients with nonaffective psychosis appear
      to have increases in pro-inflammatory cytokines. Patients characterized by
      primary, enduring negative symptoms (deficit symptoms) differ from patients
      without such features with regard to course of illness, treatment response, risk
      factors and metabolic disturbances. We hypothesized that they would also differ
      on concentrations of the inflammatory markers interleukin-6 (IL6) and C-reactive
      protein (CRP). Newly diagnosed, antipsychotic-naive patients with nonaffective
      psychosis were categorized into deficit (N=20) and nondeficit (N=42) groups, and
      were matched on age, gender, body mass index, smoking, cortisol level,
      socioeconomic status, and the severity of psychotic symptoms. Fasting
      concentrations of IL6 were significantly higher in deficit (mean [S.D.]) (8.0
      pg/ml [12.7]) than nondeficit patients (0.3 pg/ml [1.3]). CRP levels were also
      significantly higher in the deficit patients (0.3 mg/dl [0.4]) vs. (0.2 mg/dl
      [0.4]), respectively. In contrast, 2-h glucose concentrations (2HG) in a glucose
      tolerance test were lower in the deficit than the nondeficit group. Our results
      show a double dissociation with regard to glucose intolerance and inflammation:
      the deficit group has greater inflammation, but less severe glucose intolerance.
      These results provide further evidence for the validity of the deficit/nondeficit
      categorization.

PMID- 22405658
TI  - Clinical monitoring of stage B heart failure: echocardiography.
AB  - Estimates of the prevalence of asymptomatic left ventricular systolic dysfunction
      (LVSD) vary widely depending on the study sample and definition of LVSD. Subtle
      reductions in LV systolic or diastolic function are now detectable with newer
      echocardiographic measures, which can influence estimates of the burden of stage
      B heart failure (HF). If the definition is broadened to include diastolic filling
      abnormalities, the estimated prevalence of stage B HF increases dramatically.
      This article reviews the rationale for echocardiographic screening for stage B
      HF, describes currently available measures of cardiac structure and function, and
      assesses the potential role of echocardiography in selected subgroups.

PMID- 22405659
TI  - Cardiac magnetic resonance imaging for stage B heart failure.
AB  - Cardiac magnetic resonance imaging (CMR) can play a key role in the assessment
      and follow-up of patients with stage B heart failure. CMR currently serves as the
      reference standard for quantifying right and left ventricular size and ejection
      fraction. Technical advances have also enabled CMR to provide noninvasive tissue
      characterization and detailed assessments of myocardial performance. Thus, in
      addition to standard metrics of cardiac structure and function, CMR offers a
      variety of tools for determining cause, severity, and estimating the prognosis
      associated with an asymptomatic cardiomyopathy.

PMID- 22405660
TI  - Radionuclide imaging in stage B heart failure.
AB  - This article discusses currently available radionuclide techniques in the
      diagnostic and prognostic evaluation of patients with chronic heart failure, with
      a focus on stage B/asymptomatic left ventricular dysfunction. Radionuclide
      imaging is promising for such patients because it can simultaneously determine
      left ventricular function, evaluate for the presence of obstructive coronary
      disease, determine the extent of viable myocardium, and evaluate dyssynchronous
      left ventricular contraction. Radionuclide imaging can thus provide important
      noninvasive insights into the pathophysiology, prognosis, and management of
      patients with asymptomatic left ventricular dysfunction as well as more advanced
      heat failure.

PMID- 22405661
TI  - Biomarkers.
AB  - Epidemiologic, clinical, and basic research has identified several antecedent
      conditions that predispose individuals to heart failure and its predecessor,
      asymptomatic left ventricular remodeling and dysfunction (stage B heart failure).
      Many biochemical markers have been described that characterize the remodeling
      process and the development of cardiac dysfunction. Although natriuretic peptides
      and cardiac troponin are currently used in the context of diagnosis, risk
      stratification, and management of stage C and D heart failure, many other
      biomarkers provide insights into the underlying pathophysiology of left
      ventricular dysfunction, suggesting new directions for fundamental research or
      the development of new therapies.

PMID- 22405662
TI  - The role of renin angiotensin system intervention in stage B heart failure.
AB  - This article outlines the link between the renin angiotensin aldosterone system
      (RAAS) and various forms of cardiomyopathy, and also reviews the understanding of
      the effectiveness of RAAS intervention in this phase of ventricular dysfunction.
      The authors focus their discussion predominantly on patients who have had
      previous myocardial infarction or those who have left ventricular hypertrophy and
      also briefly discuss the role of RAAS activation and intervention in patients
      with alcoholic cardiomyopathy.

PMID- 22405663
TI  - beta-blockers in stage B: a precursor of heart failure.
AB  - beta-blockers are an important treatment of heart failure (HF) and are useful in
      reducing the progression of the syndrome. They should be considered for patients
      with asymptomatic left ventricular (LV) dysfunction. Evidence-based beta-blocker
      therapy (bisoprolol, carvedilol, or metoprolol succinate) in combination with
      standard therapy is a mainstay of treatment of all symptomatic patients with LV
      systolic dysfunction. Patients in stage B also benefit from the early
      introduction of beta-blockers, but there are no large randomized clinical trials
      to support this strategy. Whether there is a role for ivabradine in the treatment
      of HF is not clear.

PMID- 22405664
TI  - The role of mineralocorticoid receptor antagonists in patients with American
      College of Cardiology/American Heart Association stage B heart failure.
AB  - This article focuses on the potential role of mineralocorticoid receptor
      antagonists (MRAs) in patients with stage B heart failure (HF) due to
      hypertension, diabetes mellitus, and/or visceral obesity with the metabolic
      syndrome. It briefly discusses the role of MRAs in patients with left ventricular
      dilatation due to nonischemic or ischemic cardiomyopathy and in those with a
      prior myocardial infarction but without left ventricular dilatation or evidence
      of HF.

PMID- 22405665
TI  - Nitric oxide modulation as a therapeutic strategy in heart failure.
AB  - Nitric oxide (NO) is recognized as one of the most important cardiovascular
      signaling molecules, with multiple regulatory effects on myocardial and vascular
      tissue as well as on other tissues and organ systems. With the growth in
      understanding of the range and mechanisms of NO effects on the cardiovascular
      system, it is now possible to consider pharmaceutical interventions that directly
      target NO or key steps in NO effector pathways. This article reviews aspects of
      the cardiovascular effects of NO, abnormalities in NO regulation in heart
      failure, and clinical trials of drugs that target specific aspects of NO
      signaling pathways.

PMID- 22405666
TI  - Stage B heart failure: rationale for screening.
AB  - To adequately address the burden imposed by heart failure, a combined approach to
      prevention, early detection, and management is required. Failure to adequately
      consider the presymptomatic pool of subjects largely accounts for the continuing
      burden of incident cases of symptomatic heart failure. This article reviews the
      rationale for the early detection and management of stage B heart failure with
      specific reference to asymptomatic left ventricular systolic dysfunction as a
      potentially modifiable heart failure antecedent. Provided one can safely and
      reliably detect these individuals, a strong case can be made for screening given
      the evidence from treatment efficacy studies that clinicians can improve patient
      outcomes.

PMID- 22405667
TI  - Strategies to screen for stage B as a heart failure prevention intervention.
AB  - Heart failure (HF) prevention is an indisputably laudable goal, albeit with
      undefined global public health impact in an increasingly elderly population with
      competing cardiovascular and noncardiovascular risks for morbidity and mortality.
      The understanding of cardiac and noncardiac structural and functional
      abnormalities that predispose to the diverse clinical HF syndrome is rapidly
      advancing, and novel approaches for prevention and treatment are needed.
      Successful approaches mandate not only identification of discrete therapeutic
      targets but also research into the developing sciences of health care delivery
      and behavioral modification. Targeting Stage B HF represents one such potential
      strategy.

PMID- 22405668
TI  - Reducing the burden of stage B heart failure and the global pandemic of
      cardiovascular disease: time to go to war with the "barefoot" troops!

PMID- 22405669
TI  - Stage B, a precursor of heart failure, part II.

PMID- 22405670
TI  - The promise of pharmacogenetics in labor analgesia...tantalizing, but not there
      yet.

PMID- 22405671
TI  - The transversus abdominis plane block and post-caesarean analgesia: are we any
      closer to defining its role?

PMID- 22405672
TI  - 3rd international conference on "Nutrition and care of the preterm infant:
      current issues".

PMID- 22405673
TI  - Elective femoro-femoral cardiopulmonary bypass during transcatheter aortic valve
      implantation: a useful tool.
AB  - OBJECTIVE: Transcatheter aortic valve implantation is a new method to treat high
      risk patients with aortic valve stenosis. The operative risk can be reduced,
      especially in patients with severely reduced left ventricular function or
      cardiogenic shock. Nevertheless, this new procedure has some potential risks,
      especially during the phases of rapid pacing (valvuloplasty and valve
      deployment). The use of cardiopulmonary bypass allows the perioperative risk to
      be reduced. METHOD: Between April 2008 and August 2011, 512 consecutive patients
      underwent transcatheter aortic valve implantation. Cardiopulmonary bypass was
      used in 35 patients. In this special group, there were 17 men and 18 women with a
      mean age of 77 +/- 12 years (range, 38-92 years). Left ventricular ejection
      fraction was a mean of 32% +/- 19% (range, 10%-70%), European System for Cardiac
      Operative Risk Evaluation was 60% +/- 27% (range, 13%-97%), and Society of
      Thoracic Surgeons' mortality score was 35% +/- 28% (range, 4%-90%). RESULTS:
      Cardiopulmonary bypass was used in 13 patients with preoperative cardiogenic
      shock, 11 patients with impaired heart function during the procedure, 7 patients
      with severely impaired left ventricular function (left ventricular ejection
      fraction, 17% +/- 6%; range, 10%-30%), 3 patients with concomitant conventional
      surgical procedures, and 1 patient with impaired right ventricular function. The
      technical success rate was 94%, 30-day mortality was 20%, and 1-year survival was
      46%. CONCLUSIONS: The use of cardiopulmonary bypass enhances safety in critical
      transcatheter aortic valve implantation procedures. Furthermore, transcatheter
      aortic valve implantation with cardiopulmonary bypass seems to provide better
      results than medical therapy or conventional aortic valve replacement in
      critically ill patients. The need for cardiopulmonary bypass emphasizes that the
      procedure should be performed only in cooperation between cardiologists and
      cardiac surgeons.

PMID- 22405674
TI  - Drug-eluting stents versus coronary artery bypass graft surgery in left main
      coronary artery disease: a meta-analysis of early outcomes from randomized and
      nonrandomized studies.
AB  - OBJECTIVE: The present meta-analysis aimed to compare the short-term safety and
      efficacy of drug-eluting stents and coronary artery bypass graft surgery for
      patients with left main coronary artery disease. METHODS: Fourteen relevant
      studies were identified from 5 electronic databases. End points included
      mortality, stroke, myocardial infarction, repeat revascularization, and major
      adverse cardiac and cerebrovascular events. RESULTS: Results indicate that all
      cause mortality was similar between drug-eluting stents and coronary artery
      bypass grafting at 30 days and at follow-up beyond 1 year. Likewise, the
      incidence of myocardial infarction was similar between drug-eluting stents and
      coronary artery bypass grafting at 12 months and at follow-up beyond 1 year.
      However, drug-eluting stents were associated with a lower incidence of all-cause
      mortality at 12 months and a higher incidence of myocardial infarction at 30 days
      compared with coronary artery bypass grafting. Drug-eluting stents were
      consistently associated with a higher incidence of repeat revascularization,
      whereas coronary artery bypass grafting had a higher incidence of stroke. The
      incidence of major adverse cardiac and cerebrovascular events was similar between
      the 2 groups at 30 days but higher for drug-eluting stents at 12 months and
      beyond. CONCLUSIONS: Patients treated by drug-eluting stents in randomized
      controlled trials and observational studies in the current literature are often a
      preselected subgroup with less complex lesions compared with the overall target
      population. Results drawn from these studies should be viewed with caution.
      Coronary artery bypass grafting is associated with a lower incidence of major
      adverse cardiac and cerebrovascular events at 1 year and beyond, and thus should
      be regarded as the standard of treatment. However, drug-eluting stents may have a
      role for selected patients with percutaneously amenable left main disease who are
      poor surgical candidates.

PMID- 22405675
TI  - Risk factors for neurodevelopmental impairments in school-age children after
      cardiac surgery with full-flow cardiopulmonary bypass.
AB  - OBJECTIVE: To determine the risk factors for adverse neurodevelopmental outcomes
      in school-age children after full flow open-heart surgery for congenital heart
      disease. METHODS: The outcome was assessed in 117 children without a genetic
      comorbidity at a mean age of 10.4 +/- 2.5 years. Intelligence was assessed using
      the Raven's Progressive Matrices and neuromotor function using the Zurich
      Neuromotor Assessment. Risk factors were retrieved from detailed chart review.
      RESULTS: The mean intelligence score was 89 +/- 16, significantly lower than the
      norm (P < .001). Cerebral palsy was diagnosed in 10% of patients. Poor neuromotor
      performance (less than p10) was present in 15% to 20% of the children, depending
      on the motor task (all P < .001). Pure motor and static balance performance was
      also significantly impaired when patients with cerebral palsy were excluded (P <
      .01). Intelligence was only related to socioeconomic status (P = .006), and
      neuromotor outcome was related to the length of hospital stay and postoperative
      neurologic abnormalities (P < .03). The extracorporeal circulation time was
      related to adaptive fine motor performance (P = .05). All other variables were
      not related to outcome. CONCLUSIONS: Children without a genetic comorbidity are
      at risk of long-term intellectual and motor impairments also after full-flow
      cardiac repair. Surgery-related parameters play a less important role for adverse
      outcomes than postoperative complications. Our findings stress the importance of
      specialized follow-up assessments for all children with CHD undergoing open heart
      surgery.

PMID- 22405676
TI  - The RECOVER I: a multicenter prospective study of Impella 5.0/LD for
      postcardiotomy circulatory support.
AB  - OBJECTIVES: Cardiogenic shock after cardiac surgery is accompanied by a high
      mortality rate. Early institution of hemodynamic support with a versatile, easy
      to insert left ventricular assist device might help bridge patients to recovery
      or to the next therapy, and improve the outcomes. METHODS: Patients developing
      cardiogenic shock or low cardiac output syndrome after being weaned off
      cardiopulmonary bypass were enrolled in a prospective single-arm feasibility
      study (RECOVER I). The primary safety endpoint was the frequency of major adverse
      events (death, stroke) at 30 days or discharge, whichever was longer. The primary
      efficacy endpoint was survival of the patient to implementation of the next
      therapy, which included recovery at 30 days after device removal and bridge-to
      other-therapy. RESULTS: Sixteen patients provided informed consent and were
      enrolled in the study. Hemodynamics improved immediately after the initiation of
      mechanical support: cardiac index, 1.65 versus 2.7 L/min/m(2) (P = .0001); mean
      arterial pressure, 71.4 versus 83.1 mm Hg (P = .01); and pulmonary artery
      diastolic pressure, 28.0 versus 19.8 mm Hg (P < .0001). The pump provided an
      average of 4.0 +/- 0.6 L/min of flow for an average duration of 3.7 +/- 2.9 days
      (range, 1.7-12.6). The primary safety endpoint occurred in 2 patients (13%; 1
      stroke and 1 death). For the primary efficacy endpoint, recovery of the native
      heart function was obtained in 93% of the patients discharged, with bridge-to
      other-therapy in 7%. Survival to 30 days, 3 months, and 1 year was 94%, 81%, and
      75%, respectively. CONCLUSIONS: The use of the Impella 5.0/left direct device is
      safe and feasible in patients presenting with postcardiotomy cardiogenic shock.
      The device was rapidly inserted, enabled early support, and yielded favorable
      outcomes.

PMID- 22405677
TI  - Effects of Potamogeton crispus L. on the fate of phthalic acid esters in an
      aquatic microcosm.
AB  - To study the effects of submerged hydrophytes on the fate of dibutyl phthalate
      (DBP) and di-2-ethylexyl phthalate (DEHP) in the aquatic environment, a
      Potamogeton crispus L. (P. crispus) microcosm was constructed. A four-compartment
      (i.e., water, plant, non-rhizosphere and rhizosphere sediments) level IV fugacity
      model was established and applied to the simulation experiments in the microcosm.
      Data obtained from model calculations were in good agreement with those from the
      experiments. Results of the model calculations showed that the total residues of
      DBP and DEHP in the microcosm with P. crispus were 39.7% and 19.8% lower than
      those in the microcosm without P. crispus. The overall biodegradation fluxes of
      DBP and DEHP in the microcosm with P. crispus increased by 4.7% and 12.3%,
      respectively, and meanwhile, advective outflow decreased. In the presence of P.
      crispus, a large fraction of loaded DBP and DEHP (17.7% and 29.0%) transferred to
      plants, and then to the rhizosphere. 4.8% and 28.0% of loaded DBP and DEHP were
      removed by biodegradation in P. crispus, and the remaining 12.9% and 1.0% were by
      biodegradation in rhizosphere sediment which was 3.6% of the total sediment. This
      finding demonstrates that P. crispus can substantially reduce the accumulation of
      phthalic acid esters (PAEs) in the experiment system and enhance the removal of
      PAEs. The enhancement of PAE removal is related to the biodegradation of PAEs in
      P. crispus, especially for the more hydrophobic DEHP. For the less hydrophobic
      DBP, biodegradation in the rhizosphere also plays a key role. In addition to
      nutrient uptake from sediment, transport process between P. crispus and the
      rhizosphere has also a significant influence on the distribution and fate of PAEs
      in the aquatic environment.

PMID- 22405678
TI  - A retrospective study on imported hepatitis E in Japan.
AB  - Hepatitis E virus (HEV), a causative agent of human hepatitis E, is transmitted
      through an oral-fecal route, often by contaminated drinking water. Serum
      specimens were collected from 112 non-A, -B, and -C acute hepatitis patients from
      1989 to 2004 in Japan. Of these, 24 patients were found to be positive for anti
      HEV IgM and diagnosed with acute Hepatitis E. Seventeen of these patients had a
      clear history of traveling abroad before disease onset and were counted as cases
      of imported HEV infection. HEV RNA was detected in 16 of these imported cases,
      and the nucleotide sequences similar to those of HEV detected in India,
      Bangladesh, and China were identified. By phylogenetic analysis, the remaining
      imported case appeared to have been imported from India, even though the
      patient's travel history was uncertain. These results indicated that some
      sporadic cases of hepatitis E in Japan are caused by imported HEV, and that
      phylogenetic analyses enable us to identify the country or area where a patient
      has been infected.

PMID- 22405679
TI  - Imported cutaneous leishmaniasis in a short-term traveler returning from Central
      Mali - The role of PCR.
AB  - Leishmaniasis is a parasitic infection caused by the obligate intracellular
      protazoa leishmania. The most commonly encountered form is cutaneous
      leishmaniasis (CL), which generally manifests as a chronic, painless ulcer.
      Recent increases in the incidence of CL worldwide due in large part to increased
      immigration and international travel, combined often with the lack of familiarity
      with the disease in non-endemic settings, pose the continued problems of delayed
      diagnosis and inappropriate treatment. A case is described of imported cutaneous
      leishmaniasis occurring in a 48 year-old male who presented with multiple
      painless, progressively ulcerating lesions after returning from a one week trip
      to Bandiagara, Mali, West Africa. After four months of misdiagnoses and
      ineffective treatments, he was referred to a tropical disease specialist where
      the diagnosis was made with a skin biopsy followed by a tissue impression smear,
      culture and PCR. Appropriate treatment was initiated and the lesions resolved
      with minimal scarring. The goals of this case report are threefold: first, to
      stress the importance of associating chronic ulcers in a traveler with potential
      cutaneous leishmaniasis; second, to emphasize the clinical utility of PCR for the
      diagnosis; and third, to discuss the clinical approach to treatment.

PMID- 22405680
TI  - Interleukin-8 as a prognostic serum marker in canine mammary gland neoplasias.
AB  - Mammary gland tumors in female dogs are an excellent model for the clinic
      pathological, diagnostic and prognostic investigation of mammary neoplasias.
      Prognostic and predictive markers are effective in research and routine
      diagnosis. Interleukins play a fundamental role in cancer, with a particular
      function in tumor growth, invasion and metastatic potential. Interleukin-8 (IL-8)
      is known to possess tumorigenic and pro-angiogenic properties, and its
      overexpression is seen in a number of human tumors. IL-8 serum levels were
      determined and correlated with the clinic-pathological features and clinical
      evolution of mammary gland neoplasias in female dogs. IL-8 was measured by an
      immunoenzymatic assay in 30 female dogs with mammary neoplasias within a 12 month
      follow-up and in 50 control animals. The correlation between IL-8 concentration
      and clinical parameters was investigated. A statistically significant difference
      in the IL-8 serum levels was found in tumor-bearing dogs compared to the
      controls. In addition, when the individual parameters were evaluated, IL-8
      content showed a positive correlation with the tumor progression, lymph node
      involvement, recurrence and death. Single and multivariate analyses showed
      associations between tumor recurrence, metastasis, high clinical staging and high
      IL-8, and also with the death risk. This was also consistent with the high IL-8
      content in dogs showing tumor recurrence and metastasis. IL-8 superexpression has
      been detected in a number of human tumors, usually associated with a poor
      prognostic. Besides promoting angiogenesis, IL-8 is strongly related with the
      metastatic phenotype of mammary tumor cells. High IL-8 concentration was found in
      mammary gland cancer patients with advanced disease stages. Our results show that
      IL-8 can be used as a non-invasive prognostic marker for mammary gland cancer,
      and can be useful for the prediction of disease progression and recurrence in
      dogs with mammary neoplasias. The increased level of this cytokine acts as an
      independent prognostic marker of survival and the identification of animals with
      the poor prognostic.

PMID- 22405681
TI  - Monoclonal antibodies to equine CD23 identify the low-affinity receptor for IgE
      on subpopulations of IgM+ and IgG1+ B-cells in horses.
AB  - CD23, also called FcepsilonRII, is the low-affinity receptor for IgE and has
      first been described as a major receptor regulating IgE responses. In addition,
      CD23 also binds to CD21, integrins and MHC class II molecules and thus has a much
      wider functional role in immune regulation ranging from involvement in antigen
      presentation to multiple cytokine-like functions of soluble CD23. The role of
      CD23 during immune responses of the horse is less well understood. Here, we
      expressed equine CD23 in mammalian cells using a novel IL-4 expression system.
      Expression resulted in high yield of recombinant IL-4/CD23 fusion protein which
      was purified and used for the generation of monoclonal antibodies (mAbs) to
      equine CD23. Seven anti-CD23 mAbs were further characterized. The expression of
      the low-affinity IgE receptor on equine peripheral blood mononuclear cells was
      analyzed by flow cytometric analysis. Cell surface staining showed that CD23 is
      mainly expressed by a subpopulation of equine B-cells. Only a very few equine T
      cells or monocytes expressed CD23. CD23(+) B-cells were either IgM(+) or IgG1(+)
      cells. All CD23(+) cells were also positive for cell surface IgE staining
      suggesting in vivo IgE binding by the receptor. Two of the CD23 mAbs detected
      either the complete extracellular region of CD23 or a 22kDa cleavage product of
      CD23 by Western blotting. The new anti-CD23 mAbs provide valuable reagents to
      further analyze the roles of CD23 during immune responses of the horse in health
      and disease.

PMID- 22405682
TI  - Posteroanterior spinal stiffness at T5, T10, and L3 levels in normal subjects.
AB  - OBJECTIVE: To measure, by using standardized device and protocol, posteroanterior
      (PA) spinal stiffness at the 5th and 10th thoracic (T5 and T10) and 3rd lumbar
      (L3) vertebral levels in asymptomatic adult volunteers. DESIGN: A cross-sectional
      study. SETTING: Osteopathic Heritage Foundation Physical Medicine Core Research
      Laboratory where the Therapeutic Spinal Mobilizer was fabricated to standardize
      the testing protocol. PARTICIPANTS: Sixteen asymptomatic adult volunteers.
      METHODS: Volunteers were in the prone position on the treatment plinth and the
      loading block of the loading piston was placed at T5, T10, and L3. The subjects
      were instructed to remain still, to not contract any muscle, and to stop
      breathing mid cycle for 15 seconds when the data acquisition was initiated for a
      10-second test cycle. The force was measured by using the load cell, and the
      spinal deformation was measured by the linear variable differential transducer.
      The data were extracted and subjected to descriptive statistics and analysis of
      variance to determine the effect of independent variables on spinal stiffness.
      RESULTS: The PA spinal stiffness at 3 spinal levels was significantly different
      (P < .0001). The spinal stiffness was significantly affected by the testing load,
      age, gender, and body weight of the subjects (P < .0001). The PA stiffness of the
      entire sample at 3 spinal levels ranged from 4.8-8.8 N/mm. The spinal stiffness
      values could be predicted as the function of testing load and body weight (P <
      .01). CONCLUSIONS: Results of this experiment suggest that the standardized and
      repeatable methodology will result in reliable stiffness values. Because the
      spinal stiffness is an indicator of patient's symptoms and it is an important
      variable in selection of treatment regimen, it is important to be able to measure
      this variable with a standardized protocol. Values from asymptomatic subjects can
      be used to study and to compare the symptomatic patients.

PMID- 22405683
TI  - Randomized controlled trial comparing acupuncture with placebo acupuncture for
      the treatment of carpal tunnel syndrome.
AB  - OBJECTIVE: To investigate the efficacy of acupuncture for the treatment of mild
      to moderate carpal tunnel syndrome (CTS). DESIGN: Prospective, randomized,
      placebo-controlled, double-blinded study. SETTING: Single-center study.
      PARTICIPANTS: Forty-one acupuncture-naive adult subjects with mild to moderate
      CTS enrolled in the study. Thirty-four subjects completed the study. METHODS:
      Clinical diagnosis of CTS was supported by electrodiagnostic findings. Subjects
      were randomly assigned to either (1) acupuncture (n = 21) or (2) placebo
      acupuncture (n = 20) with use of Streitberger placebo acupuncture needles. Both
      groups received weekly sessions of acupuncture for 6 weeks. Wrist braces were
      provided to both groups to wear at night, and compliance was monitored. MAIN
      OUTCOME MEASUREMENTS: The primary outcome measurement was subject-reported change
      in the Carpal Tunnel Self Assessment Questionnaire (CTSAQ) Symptom and Function
      scales immediately after and at 2 weeks and 3 months after the final treatment.
      The secondary outcomes included tip and key pinch strength and combined sensory
      index. RESULTS: Compared with pretreatment baseline values, subjects in the
      acupuncture group had 0.58 improvement (P = .03) on the CTSAQ Symptom scale score
      at 3 months after the last treatment, whereas 0.81 improvement (P = .001) was
      noted in the placebo acupuncture group. No statistically significant difference
      was found between the groups treated with acupuncture and placebo acupuncture
      with respect to improvement in CTS symptoms, function, tip/key pinch, or combined
      sensory index. CONCLUSIONS: To our knowledge, this study is the first randomized,
      placebo-controlled, double-blinded prospective study of traditional acupuncture
      for CTS. Both the treatment and placebo groups demonstrated improvements from
      baseline. Acupuncture was not shown to be superior to placebo acupuncture when
      used in conjunction with bracing for patients with mild to moderate CTS.

PMID- 22405684
TI  - Exercise recommendations in patients with newly diagnosed fibromyalgia.
AB  - OBJECTIVE: To evaluate exercise recommendations in patients newly diagnosed with
      fibromyalgia. DESIGN: A retrospective chart review. SETTING: A public university
      rheumatology clinic. PATIENTS: Patients newly diagnosed with fibromyalgia (N =
      122). MAIN OUTCOME MEASUREMENTS: Frequency and type of exercise recommendations.
      RESULTS: The mean (standard deviation) age of these patients with fibromyalgia
      was 45 +/- 12 years; 91% were women. Exercise was recommended as part of the
      documented treatment plan in 47% of these patients (57/122); only 3 patients had
      a documented contraindication for exercise. Aquatic exercise was most frequently
      recommended (56% [32/57]), followed by combined aquatic-aerobic exercise (26%
      [15/57]), and, infrequently, aerobic exercise only (5% [3/57]); only 7% of these
      patients (4/57) were referred for physical therapy. The primary method of
      communication was verbal discussion (94% [54/57]). CONCLUSIONS: Although there is
      well-documented evidence that exercise is beneficial for patients with
      fibromyalgia, we found that less than half of patients with newly diagnosed
      fibromyalgia in our study were provided recommendations to initiate an exercise
      program as part of their treatment plan. Further investigation of these findings
      are warranted, including evaluation of other university and community
      rheumatology practices as well as that of other physicians caring for patients
      with fibromyalgia. However, our findings indicate that there appears to be an
      opportunity to provide more specific and practical education regarding the
      implementation of an exercise regimen for patients with newly diagnosed
      fibromyalgia. Physiatrists may be particularly well suited to manage the exercise
      component of patients with fibromyalgia because of their specialized training in
      exercise prescription.

PMID- 22405685
TI  - Does computed tomography rule out clinically significant cervical spine injuries
      in obtunded or intubated blunt trauma patients? [corrected].

PMID- 22405686
TI  - Associations between perceived neighborhood environmental attributes and adults'
      sedentary behavior: findings from the U.S.A., Australia and Belgium.
AB  - Sedentary behaviors are associated with multiple health problems, independently
      of physical activity. Neighborhood environment attributes might influence
      sedentary behaviors, but few studies have investigated these relationships.
      Moreover, all previous studies have been conducted within single countries,
      limiting environmental variability. We investigated the shape of associations
      between perceived neighborhood environment attributes and sedentary behavior in
      three countries; and whether these associations differed by country and gender.
      Data from U.S.A. (Seattle and Baltimore regions), Australia (Adelaide) and
      Belgium (Ghent) were pooled. Data collection took place between 2002 and 2008. In
      total, 6014 adults (20-65 years, 55.7% women) were recruited in high-/low
      walkability and high-/low-income neighborhoods. All participants completed the
      International Physical Activity Questionnaire (domain-specific physical activity,
      transport-related sitting and overall time spent sitting) and the Neighborhood
      Environmental Walkability Scale (environmental perceptions). The number of
      destinations within a 20 min walk from home, perceiving few cul-de-sacs, good
      walking and cycling facilities, and traffic safety were included in an index of
      motorized transport correlates. This index was linearly negatively associated
      with motorized transport time, so the higher the scores on the index (more
      activity-friendliness), the lower the amount of motorized transport. No gender-
      or country-differences were identified. Perceived aesthetics and proximity of
      destinations were included in an index of overall sitting time correlates. A
      linear negative relationship with overall sitting time was found, but
      associations were stronger for men and not significant in Belgian adults. In
      conclusion, consistent and expected correlates were found for motorized transport
      in the three countries, but results were less clear for overall sitting time.
      Future studies should include even more countries to maximize environmental
      variability, but present findings suggest that neighborhoods may be designed to
      improve health through supporting more active and less sedentary transportation,
      which can be expected to have health benefits.

PMID- 22405687
TI  - Adolescent expectations of early death predict young adult socioeconomic status.
AB  - Among adolescents, expectations of early death have been linked to future risk
      behaviors. These expectations may also reduce personal investment in education
      and training, thereby lowering adult socioeconomic status attainment. The
      importance of socioeconomic status is highlighted by pervasive health inequities
      and dramatic differences in life expectancy among education and income groups.
      The objectives of this study were to investigate patterns of change in perceived
      chances of living to age 35 (Perceived Survival Expectations; PSE), predictors of
      PSE, and associations between PSE and future socioeconomic status attainment. We
      utilized the U.S. National Longitudinal Study of Adolescent Health (Add Health)
      initiated in 1994-1995 among 20,745 adolescents in grades 7-12 with follow-up
      interviews in 1996 (Wave II), 2001-2002 (Wave III) and 2008 (Wave IV; ages 24
      32). At Wave I, 14% reported <=50% chance of living to age 35 and older
      adolescents reported lower PSE than younger adolescents. At Wave III, PSE were
      similar across age. Changes in PSE from Wave I to III were moderate, with 89% of
      respondents reporting no change (56%), one level higher (22%) or one level lower
      (10%) in a 5-level PSE variable. Higher block group poverty rate, perceptions
      that the neighborhood is unsafe, and less time in the U.S. (among the foreign
      born) were related to low PSE at Waves I and III. Low PSE at Waves I and III
      predicted lower education attainment and personal earnings at Wave IV in
      multinomial logistic regression models controlling for confounding factors such
      as previous family socioeconomic status, individual demographic characteristics,
      and depressive symptoms. Anticipation of an early death is prevalent among
      adolescents and predictive of lower future socioeconomic status. Low PSE reported
      early in life may be a marker for worse health trajectories.

PMID- 22405688
TI  - Does SES explain more of the black/white health gap than we thought? Revisiting
      our approach toward understanding racial disparities in health.
AB  - Studies of racial health gaps often find that disparities persist even after
      adjusting for socioeconomic status (SES). We contend that the persistent residual
      variation may, in part, be the result of conceptual and methodological problems
      in the operationalization of SES. These include inadequate attention to the
      content validity of SES measures and insufficient adjustments for SES differences
      across racial groups. Using data from the 1997-2007 U.S. Panel Study of Income
      Dynamics (N = 9932), we use longitudinal and multi-level measures of SES and
      apply a propensity score adjustment strategy to examine the black/white disparity
      in self-rated health. Compared to conventional regression estimates that yield
      unexplained racial health gaps, propensity score adjustment accounts for the
      entire racial disparity in self-rated health. Results suggest that previous
      studies may have inadequately adjusted for differences in SES across racial
      groups, that social factors should be carefully and conscientiously considered,
      and that acknowledgment of the possibility of incomplete SES adjustments should
      be weighed before any inferences to non-SES etiology can be made.

PMID- 22405689
TI  - Taste neophobia and c-Fos expression in the rat brain.
AB  - Taste neophobia refers to a reduction in consumption of a novel taste relative to
      when it is familiar. To gain more understanding of the neural basis of this
      phenomenon, the current study examined whether a novel taste (0.5% saccharin)
      supports a different pattern of c-Fos expression than the same taste when it is
      familiar. Results revealed that the taste of the novel saccharin solution evoked
      more Fos immunoreactivity than the familiar taste of saccharin in the basolateral
      region of the amygdala, central nucleus of the amygdala, gustatory portion of the
      thalamus, and the gustatory insular cortex. No such differential expression was
      found in the other examined areas, including the bed nucleus of stria
      terminalis,medial amygdala, and medial parabrachial nucleus. The present results
      are discussed with respect to a forebrain taste neophobia system.

PMID- 22405690
TI  - Differential alterations of synaptic plasticity in dentate gyrus and CA1
      hippocampal area of Calbindin-D28K knockout mice.
AB  - Regulation of the intracellular calcium concentration ([Ca(2+)](i)) is of
      critical importance for synaptic function. Therefore, neurons buffer [Ca(2+)](i)
      using intracellular Ca(2+)-binding proteins (CaBPs). Previous evidence suggests
      that Calbindin-D(28K) (CB), an abundantly expressed endogenous fast CaBP, plays
      an important role in neuronal survival, motor coordination, spatial learning
      paradigms and some forms of synaptic plasticity. In the present study, the role
      of CB in synaptic transmission and plasticity was further investigated using
      extracellular recordings of synaptic activity in cell- and dendritic layers of
      dentate gyrus (DG) and CA1 area in hippocampal slices from wild-type,
      heterozygous and homozygous CB knockout mice. The results demonstrate a
      consistent failure to maintain long-term potentiation (LTP) in hippocampal DG and
      CA1 area of knockout mice. Compared to wild-type mice, the paired-pulse ratio of
      EPSPs recorded in DG is significantly lower in slices from knockout mice, whereas
      it is significantly higher in CA1 area. The amplitude of the population spike
      recorded in CA1 area of wild-type mice steadily increases following tetanic
      stimulation, whereas it steadily decreases in knockout mice. The combined results
      demonstrate that the absence of CB results in an impairment of LTP maintenance in
      both hippocampal DG and CA1 area, whereas paired-pulse facilitation and cellular
      excitability in CA1 area are differentially affected. These results support the
      role of CB as a critical determinant for several forms of synaptic plasticity in
      hippocampal DG and CA1 area. It is hypothesized that CB functions as a
      postsynaptic Ca(2+) buffer as well as a presynaptic Ca(2+) sensor.

PMID- 22405691
TI  - Suppressive effect of preconditioning low-frequency stimulation on subsequent
      induction of long-term potentiation by high frequency stimulation in hippocampal
      CA3 neurons.
AB  - We investigated the role of inositol 1, 4, 5-trisphosphate receptors (IP3Rs),
      activated during preconditioning low-frequency afferent stimulation (LFS), in the
      subsequent induction of long-term potentiation (LTP) in CA3 neurons in
      hippocampal slices from mature guinea pigs. Induction of LTP in the field
      excitatory postsynaptic potential (EPSP) by the delivery of high-frequency
      stimulation (HFS, a tetanus of two trains of 100 pulses at 100Hz with a 10s
      interval) to mossy fiber-CA3 neuron synapses was suppressed when CA3 synapses
      were preconditioned by the LFS of 1000 pulses at 2Hz and this effect was
      inhibited when the LFS preconditioning was performed in the presence of an IP3R
      antagonist or a protein phosphatase inhibitor. Furthermore, activation of group 1
      metabotropic glutamate receptors (mGluRs) during HFS canceled the effects of an
      IP3R antagonist given during preconditioning LFS on the subsequent LTP induction
      at mossy fiber-CA3 synapses. These results suggest that, in hippocampal mossy
      fiber-CA3 neuron synapses, activation of IP3Rs during a preconditioning LFS
      results in dephosphorylation events that lead to failure of the HFS to induce
      subsequent LTP.

PMID- 22405693
TI  - [Whole brain radiotherapy for brain metastases: the technique of irradiation
      influences the dose to parotid glands].
AB  - In the treatment of brain metastases, whole brain radiotherapy can be carried out
      according two distinct methods: one using multileaf collimator for field shaping
      and protection of organs at risk, and a second one is to make a rotation of the
      field to avoid the eyes. The aim of the study was to compare for 10 patients the
      dose distributions at organs at risk for each method. Patients received 30 Gy in
      10 fractions. Except for parotid glands, the dose received by organs at risk and
      the planning target volume was the same with each method. For whole brain
      radiotherapy, excluding the cisterna cerebellomedullaris, the mean parotid dose
      was 9.63 Gy using the multileaf collimator versus 12.32 Gy using the field
      rotation (P=0.04). For whole brain radiotherapy including the cisterna
      cerebellomedullaris, the mean parotid dose was 11.12 Gy using the multileaf
      collimator versus 20.06 Gy using field rotation (P<0.001). Using the multileaf
      collimator seems recommended for whole brain radiotherapy, to reduce the dose to
      the parotids.

PMID- 22405695
TI  - Comparison of high-protein diets and leucine supplementation in the prevention of
      metabolic syndrome and related disorders in mice.
AB  - High-protein diets have been shown to promote weight loss, to improve glucose
      homeostasis and to increase energy expenditure and fat oxidation. We aimed to
      study whether leucine supplementation is able to mimic the alleviating effects of
      high-protein diets on metabolic syndrome parameters in mice fed high-fat diet.
      Male C57BL/6 mice were fed for 20 weeks with semisynthetic high-fat diets (20%
      w/w of fat) containing either an adequate (10% protein, AP) or high (50% protein,
      HP) amount of whey protein, or an AP diet supplemented with L-leucine
      corresponding to the leucine content of the HP diet (6% leucine, AP+L). Body
      weight and composition, energy expenditure, glucose tolerance, hepatic
      triacylglycerols (TG), plasma parameters as well as expression levels of mRNA and
      proteins in different tissues were measured. HP feeding resulted in decreased
      body weight, body fat and hepatic TG accumulation, as well as increased insulin
      sensitivity compared to AP. This was linked to an increased total and resting
      energy expenditure (REE), decreased feed energy efficiency, increased skeletal
      muscle (SM) protein synthesis, reduced hepatic lipogenesis and increased white
      fat lipolysis. Leucine supplementation had effects that were intermediate between
      HP and AP with regard to body composition, liver TG content, insulin sensitivity,
      REE and feed energy efficiency, and similar effects as HP on SM protein
      synthesis. However, neither HP nor AP+L showed an activation of the mammalian
      target of rapamycin pathway in SM. Leucine supplementation had no effect on liver
      lipogenesis and white fat lipolysis compared to AP. It is concluded that the
      essential amino acid leucine is able to mimic part but not all beneficial
      metabolic effects of HP diets.

PMID- 22405692
TI  - Targeting inhibitory neurotransmission in tinnitus.
AB  - Tinnitus perception depends on the presence of its neural correlates within the
      auditory neuraxis and associated structures. Targeting specific circuits and
      receptors within the central nervous system in an effort to relieve the
      perception of tinnitus and its impact on one's emotional and mental state has
      become a focus of tinnitus research. One approach is to upregulate endogenous
      inhibitory neurotransmitter levels (e.g., glycine and GABA) and selectively
      target inhibitory receptors in key circuits to normalize tinnitus
      pathophysiology. Thus, the basic functional and molecular properties of two major
      ligand-gated inhibitory receptor systems, the GABA(A) receptor (GABA(A)R) and
      glycine receptor (GlyR) are described. Also reviewed is the rationale for
      targeting inhibition, which stems from reported tinnitus-related homeostatic
      plasticity of inhibitory neurotransmitter systems and associated enhanced
      neuronal excitability throughout most central auditory structures. However, the
      putative role of the medial geniculate body (MGB) in tinnitus has not been
      previously addressed, specifically in terms of its inhibitory afferents from
      inferior colliculus and thalamic reticular nucleus and its GABA(A)R functional
      heterogeneity. This heterogeneous population of GABA(A)Rs, which may be altered
      in tinnitus pathology, and its key anatomical position in the auditory CNS make
      the MGB a compelling structure for tinnitus research. Finally, some selective
      compounds, which enhance tonic inhibition, have successfully ameliorated tinnitus
      in animal studies, suggesting that the MGB and, to a lesser degree, the auditory
      cortex may be their primary locus of action. These pharmacological interventions
      are examined in terms of their mechanism of action and why these agents may be
      effective in tinnitus treatment. This article is part of a Special Issue
      entitled: Tinnitus Neuroscience.

PMID- 22405694
TI  - Polyphenols in brewed green tea inhibit prostate tumor xenograft growth by
      localizing to the tumor and decreasing oxidative stress and angiogenesis.
AB  - It has been demonstrated in various animal models that the oral administration of
      green tea (GT) extracts in drinking water can inhibit tumor growth, but the
      effects of brewed GT on factors promoting tumor growth, including oxidant damage
      of DNA and protein, angiogenesis and DNA methylation, have not been tested in an
      animal model. To explore these potential mechanisms, brewed GT was administered
      instead of drinking water to male severe combined immunodeficiency (SCID) mice
      with androgen-dependent human LAPC4 prostate cancer cell subcutaneous xenografts.
      Tumor volume was decreased significantly in mice consuming GT, and tumor size was
      significantly correlated with GT polyphenol (GTP) content in tumor tissue. There
      was a significant reduction in hypoxia-inducible factor 1-alpha and vascular
      endothelial growth factor protein expression. GT consumption significantly
      reduced oxidative DNA and protein damage in tumor tissue as determined by 8
      hydroxydeoxyguanosine/deoxyguanosine ratio and protein carbonyl assay,
      respectively. Methylation is known to inhibit antioxidative enzymes such as
      glutathione S-transferase pi to permit reactive oxygen species promotion of tumor
      growth. GT inhibited tumor 5-cytosine DNA methyltransferase 1 mRNA and protein
      expression significantly, which may contribute to the inhibition of tumor growth
      by reactivation of antioxidative enzymes. This study advances our understanding
      of tumor growth inhibition by brewed GT in an animal model by demonstrating
      tissue localization of GTPs in correlation with inhibition of tumor growth. Our
      results suggest that the inhibition of tumor growth is due to GTP-mediated
      inhibition of oxidative stress and angiogenesis in the LAPC4 xenograft prostate
      tumor in SCID mice.

PMID- 22405696
TI  - Perinatal undernutrition alters intestinal alkaline phosphatase and its main
      transcription factors KLF4 and Cdx1 in adult offspring fed a high-fat diet.
AB  - Nutrient restriction during gestation and/or suckling is associated with an
      increased risk of developing inflammation, obesity and metabolic diseases in
      adulthood. However, the underlying mechanisms, including the role of the small
      intestine, are unclear. We hypothesized that intestinal adaptation to the diet in
      adulthood is modulated by perinatal nutrition. This hypothesis was tested using a
      split-plot design experiment with 20 controls and 20 intrauterine growth-retarded
      (IUGR) rats aged 240 days and randomly assigned to be fed a standard chow or a
      high-fat (HF) diet for 10 days. Jejunal tissue was collected at necropsy and
      analyzed for anatomy, digestive enzymes, goblet cells and mRNA levels. Cecal
      contents and blood serum were analyzed for alkaline phosphatase (AP). IUGR rats
      failed to adapt to HF by increasing AP activity in jejunal tissue and cecal
      content as observed in controls. mRNA levels of transcription factors KLF4 and
      Cdx1 were blunted in jejunal epithelial cell of IUGR rats fed HF. mRNA levels of
      TNF-alpha were lower in IUGR rats. They also displayed exacerbated aminopeptidase
      N response and reduced jejunal goblet cell density. Villus and crypt architecture
      and epithelial cell proliferation increased with HF in both control and IUGR
      rats. Serum AP tended to be lower, and serum levamisole inhibition-resistant AP
      fraction was lower, in IUGR than controls with HF. Serum fatty acids and
      triglycerides were higher in IUGR rats and higher with HF. In conclusion, the
      adult intestine adapts to an HF diet differentially depending on early nutrition,
      jejunal AP and transcription factors being blunted in IUGR individuals fed HF.

PMID- 22405697
TI  - Thiacremonone, a sulfur compound isolated from garlic, attenuates lipid
      accumulation partially mediated via AMPK activation in 3T3-L1 adipocytes.
AB  - Garlic extracts exert anti-cancer and anti-inflammatory effects. However, the
      anti-adipogenic effect of garlic-derived compounds remains unclear. In this
      study, we examined the effect of thiacremonone, a sulfur compound isolated from
      garlic, on adipocyte differentiation using 3T3-L1 cells. We found that
      thiacremonone significantly inhibited 3T3-L1 differentiation via down-regulation
      of adipogenesis-related transcription factors and adipogenic markers. The
      inhibitory effect mainly occurred at the early phase of differentiation in 3T3-L1
      cells. There was no cytotoxic effect of thiacremonone in 3T3-L1 cells and
      treatment of differentiating 3T3-L1 cells with thiacremonone resulted in AMPK
      activation, which led to an attenuated expression of acetyl CoA carboxylase-1
      (ACC-1), an essential enzyme for the synthesis and usage of fatty acids.
      Moreover, thiacremonone enhanced the mRNA level of carnitine palmitoyltransferase
      (CPT-1). The modulating effect of thiacremonone on expressions of genes involved
      in lipolysis was partially abrogated by treatment with compound C, an AMPK
      inhibitor. Taken together, these results indicated that thiacremonone-induced
      AMPK activation, inhibition of ACC-1 expression and concomitant recovery of CPT-1
      expression resulted in the suppression of intracellular lipid droplet levels,
      suggesting that thiacremonone may induce reduction of lipid synthesis and
      increases in fatty acid oxidation partially mediated via AMPK activation.
      Thiacremonone may be a promising compound for the treatment of obesity.

PMID- 22405698
TI  - Prevalence of advanced histological features in diminutive and small colon
      polyps.
AB  - BACKGROUND: Investigators have proposed "predict, resect, and discard" strategies
      for diminutive (<= 5 mm) or small (6-9 mm) polyps to reduce screening colonoscopy
      costs. Advanced histological features such as villous histology, high-grade
      dysplasia, and/or cancer in these polyps could deter adoption of these
      strategies. OBJECTIVE: Determine the prevalence of advanced histological features
      in diminutive and small colon polyps. DESIGN: Retrospective analysis of data from
      3 prospective clinical trials. SETTING: Two tertiary-care referral centers.
      PATIENTS: This study involved patients undergoing screening or surveillance
      colonoscopy. INTERVENTION: The location, size, and morphology of each polyp
      detected was documented. Each polyp was then resected, placed in a unique
      specimen jar, and sent for histopathological evaluation. MAIN OUTCOME
      MEASUREMENTS: Rates of advanced histological features (villous histology, high
      grade dysplasia, and cancer). RESULTS: A total of 2361 polyps were detected,
      removed, and retrieved. Both diminutive and small polyps had a lower frequency of
      any advanced histological features compared with large polyps (0.5% and 1.5%,
      respectively vs 15.0%; P < .001 for both comparisons). Polyps <10 mm in size had
      a lower frequency of advanced histology compared with polyps >= 10 mm (0.8% vs
      15.0%; P < .001). During sensitivity analysis, the frequency of advanced
      histological features varied from 0.2% to 0.7% within diminutive polyps, 1.5% to
      3.6% within small polyps, and 0.8% to 1.2% within polyps <10 mm. LIMITATIONS:
      Retrospective analysis from tertiary-care referral centers; predominantly white,
      male, veteran patient population resulting in limited generalizability of
      results. CONCLUSION: The prevalence of advanced histological features in colon
      polyps <= 5 mm is very low (0.5%). This has important implications for the
      potential practice of "predicting, resecting, and discarding" diminutive colon
      polyps.

PMID- 22405699
TI  - Biopsy diagnosis of intraductal carcinoma is prognostic in intermediate and high
      risk prostate cancer patients treated by radiotherapy.
AB  - AIM: We investigated the prognostic significance of intraductal carcinoma of the
      prostate (IDC-P) in biopsies and transurethral resections prior to external beam
      radiotherapy with or without androgen deprivation. METHODS: Cohort 1 consisted of
      118 intermediate risk prostate cancer patients treated by radiotherapy, with
      biochemical relapse as primary end-point (median follow-up 6.5 years). Cohort 2
      consisted of 132 high risk patients, enrolled in a phase III randomised trial
      (EORTC 22863) comparing radiotherapy alone to radiotherapy with long-term
      androgen deprivation (LTAD) with clinical progression free survival as primary
      end-point (median follow-up 9.1 years). Presence of IDC-P was identified after
      central review. Multivariable regression modelling and Kaplan-Meier analysis were
      performed with IDC-P as dichotomous variable. RESULTS: IDC-P was a strong
      prognosticator for early (<36 months) biochemical relapse (HR 7.3; p = 0.007) in
      cohort 1 and for clinical disease-free survival in both arms of cohort 2
      (radiotherapy arm: HR 3.5; p < 0.0001; radiotherapy plus LTAD arm: HR 2.8, p =
      0.018). IDC-P retained significance after stratification for reviewed Gleason
      score in the radiotherapy arm (HR 2.3; p = 0.03). IDC-P was a strong
      prognosticator for metastatic failure rate (radiotherapy arm: HR 5.3; p < 0.0001;
      radiotherapy plus LTAD arm: HR 3.6; p = 0.05). CONCLUSIONS: IDC-P in diagnostic
      samples of patients with intermediate or high risk prostate cancer is an
      independent prognosticator of early biochemical relapse and metastatic failure
      rate after radiotherapy. We suggest that the presence of IDC-P in prostate
      biopsies should routinely be reported.

PMID- 22405700
TI  - Population attributable risk of aflatoxin-related liver cancer: systematic review
      and meta-analysis.
AB  - BACKGROUND: Over 4 billion people worldwide are exposed to dietary aflatoxins,
      which cause liver cancer (hepatocellular carcinoma, HCC) in humans. However, the
      population attributable risk (PAR) of aflatoxin-related HCC remains unclear.
      METHODS: In our systematic review and meta-analysis of epidemiological studies,
      summary odds ratios (ORs) of aflatoxin-related HCC with 95% confidence intervals
      were calculated in HBV+ and HBV- individuals, as well as the general population.
      We calculated the PAR of aflatoxin-related HCC for each study as well as the
      combined studies, accounting for HBV status. RESULTS: Seventeen studies with 1680
      HCC cases and 3052 controls were identified from 479 articles. All eligible
      studies were conducted in China, Taiwan, or sub-Saharan Africa. The PAR of
      aflatoxin-related HCC was estimated at 17% (14-19%) overall, and higher in HBV+
      (21%) than HBV- (8.8%) populations. If the one study that contributed most to
      heterogeneity in the analysis is excluded, the summarised OR of HCC with 95% CI
      is 73.0 (36.0-148.3) from the combined effects of aflatoxin and HBV, 11.3 (6.75
      18.9) from HBV only and 6.37 (3.74-10.86) from aflatoxin only. The PAR of
      aflatoxin-related HCC increases to 23% (21-24%). The PAR has decreased over time
      in certain Taiwanese and Chinese populations. CONCLUSIONS: In high exposure
      areas, aflatoxin multiplicatively interacts with HBV to induce HCC; reducing
      aflatoxin exposure to non-detectable levels could reduce HCC cases in high-risk
      areas by about 23%. The decreasing PAR of aflatoxin-related HCC reflects the
      benefits of public health interventions to reduce aflatoxin and HBV.

PMID- 22405701
TI  - Complementary feeding messages that target cultural barriers enhance both the use
      of lipid-based nutrient supplements and underlying feeding practices to improve
      infant diets in rural Zimbabwe.
AB  - Supplementation with lipid-based nutrient supplements (LiNS) is promoted as an
      approach to prevent child undernutrition and growth faltering. Previous LiNS
      studies have not tested the effects of improving the underlying diet prior to
      providing LiNS. Formative research was conducted in rural Zimbabwe to develop
      feeding messages to improve complementary feeding with and without LiNS. Two
      rounds of Trials of Improved Practices were conducted with mothers of infants
      aged 6-12 months to assess the feasibility of improving infant diets using (1)
      only locally available resources and (2) locally available resources plus 20 g of
      LiNS as Nutributter(r)/day. Common feeding problems were poor dietary diversity
      and low energy density. Popular improved practices were to process locally
      available foods so that infants could swallow them and add processed local foods
      to enrich porridges. Consumption of beans, fruits, green leafy vegetables, and
      peanut/seed butters increased after counselling (P < 0.05). Intakes of energy,
      protein, vitamin A, folate, calcium, iron and zinc from complementary foods
      increased significantly after counselling with or without the provision of
      Nutributter (P < 0.05). Intakes of fat, folate, iron, and zinc increased only
      (fat) or more so (folate, iron, and zinc) with the provision of Nutributter (P <
      0.05). While provision of LiNS was crucial to ensure adequate intakes of iron and
      zinc, educational messages that were barrier-specific and delivered directly to
      mothers were crucial to improving the underlying diet.

PMID- 22405702
TI  - The association between self perceptions of psychological well-being and
      overweight in Brazilian children.
AB  - Our objective was to estimate the prevalence and test the association between
      psychological well-being and overweight in children. We conducted a cross
      sectional study using anthropometrical measures and interviews with 1048 6-10
      year-old school children from a Brazilian town. Overweight was assessed by the
      body mass index and included obesity. Psychological data of children and their
      parents were collected using a face scale. Poisson regression models were used to
      test the associations and to obtain unadjusted and adjusted prevalence ratios
      (PR). The prevalence of overweight was of 15.3% (95% CI: 13.2-17.6) and of only
      obesity was 3.8% (2.8-5.2). After controlling for age, sex, school type and
      parental overweight, the prevalence of overweight was 52% and 44% higher in
      children who reported a psychological dissatisfaction in themselves and in their
      mothers when compared with those with positive self perception (PR = 1.52 95% CI
      = 1.02-2.28; P = 0.038) and (PR = 1.44 95% CI = 1.00-2.09; P = 0.049),
      respectively. The study suggests that actions aiming weight control of children
      should take into account psychological aspects of children and their families.

PMID- 22405704
TI  - Modulation of sensory-motor integration as a general mechanism for context
      dependence of behavior.
AB  - Social communication is context-dependent, with both the production of signals
      and the responses of receivers tailored to each animal's internal needs and
      external environmental conditions. We propose that this context dependence arises
      because of neural modulation of the sensory-motor transformation that underlies
      the social behavior. Neural systems that are restricted to individual behaviors
      may be modulated at early stages of the sensory or motor pathways for optimal
      energy expenditure. However, when neural systems contribute to multiple important
      behaviors, we argue that the sensory-motor relay is the likely site of
      modulation. Plasticity in the sensory-motor relay enables subtle context
      dependence of the social behavior while preserving other functions of the sensory
      and motor systems. We review evidence that the robust responses of anurans to
      conspecific signals are dependent on reproductive state, sex, prior experience,
      and current context. A well-characterized midbrain sensory-motor relay
      establishes signal selectivity and gates locomotive responses to sound. The
      social decision-making network may modulate this auditory-motor transformation to
      confer context dependence of anuran reproductive responses to sound. We argue
      that similar modulation may be a general mechanism by which vertebrates
      prioritize their behaviors.

PMID- 22405705
TI  - Secretory patterns of catecholamines in Indo-Pacific bottlenose dolphins.
AB  - Catecholamines (CAs), namely adrenaline (A), noradrenaline (NA), and dopamine
      (DA), are secreted by the sympathoadrenal system and participate in a diverse
      array of functions, e.g., heat production, cardiovascular regulation, stress
      response and so on. However, little is known regarding peripheral CA fluctuations
      in cetaceans; nevertheless aquatic animals like them have needed to modify their
      physiological response especially for thermoregulation in water and oxygen
      economy during diving. To understand CA dynamism in cetaceans, diurnal changes in
      serum A, NA, and DA concentrations were measured during the winter and summer
      solstices in four Indo-Pacific bottlenose dolphins (Tursiops aduncus). The
      average serum NA concentration was much higher than the average A and DA
      concentrations, and all concentrations were higher than those reported in other
      cetacean species. No distinct diurnal fluctuations were observed in CA
      concentrations in either solstice, suggesting inhibition of the decrease in CA
      concentrations during nocturnal periods by the unique sleep pattern of dolphins.
      All the serum CA concentrations were negatively correlated with water temperature
      as body temperatures were, indicating that the sympathoadrenal system might be
      more active during winter than in summer season, suggesting a role of CA in
      thermoregulation.

PMID- 22405706
TI  - The effect of a school-based active commuting intervention on children's
      commuting physical activity and daily physical activity.
AB  - OBJECTIVE: To investigate the effect of a school-based intervention called
      Travelling Green (TG) on children's walking to and from school and total daily
      physical activity. METHOD: A quasi-experiment with 166 Scottish children (8-9
      years) was conducted in 2009. One group (n=79) received TG and another group
      (n=87) acted as a comparison. The intervention lasted 6 weeks and consisted of
      educational lessons and goal-setting tasks. Steps and MVPA (daily, a.m. commute,
      p.m. commute, and total commute) were measured for 5 days pre- and post
      intervention using accelerometers. RESULTS: Mean steps (daily, a.m., p.m., and
      total commute) decreased from pre- to post-intervention in both groups (TG by
      901, 49, 222, and 271 steps/day and comparison by 2528, 205, 120, and 325
      steps/day, respectively). No significant group by time interactions were found
      for a.m., p.m., and total commuting steps. A medium (partial eta squared=0.09)
      and significant (p<0.05) group by time interaction was found for total daily
      steps. MVPA results were similar to step results. CONCLUSIONS: TG has a little
      effect on walking to and from school. However, for total daily steps and daily
      MVPA, TG results in a smaller seasonal decrease than for children who do not
      receive the intervention.

PMID- 22405707
TI  - Pilot study of a dog walking randomized intervention: effects of a focus on
      canine exercise.
AB  - OBJECTIVE: The promotion of dog walking among owners who do not walk their dogs
      regularly may be a viable physical activity intervention aperture, yet research
      is very limited and no intervention studies have employed control groups.
      Therefore, the purpose of this pilot study was to examine the viability of dog
      walking for physical activity intervention using messages targeting canine
      exercise. METHOD: Inactive dog owners (n=58) were randomized to either a standard
      control condition or the intervention (persuasive material about canine health
      from walking and a calendar to mark walks) after completing a baseline
      questionnaire package and wearing a pedometer for one week. Participants
      (standard condition n=28; intervention condition n=30) completed the six and 12
      week follow-up questionnaire packages. RESULTS: Intention to treat analyses
      showed that both groups increased physical activity significantly across the 12
      weeks (eta(2)=0.09 to 0.21). The intervention group resulted in significantly
      higher step-counts compared to the control group (Delta 1823 steps) and showed
      significantly higher trajectories from baseline to 12 weeks in the self-reported
      physical activity measures (eta(2)=0.11 to 0.27). CONCLUSION: The results are
      promising for the viability of increasing dog walking as a means for physical
      activity promotion and suggest that theoretical fidelity targeting canine
      exercise may be a helpful approach.

PMID- 22405708
TI  - Effects of alcohol use and abuse on critically ill burn patients.

PMID- 22405709
TI  - Psychiatric and addiction consultation for patients in critical care.
AB  - Practicing within the paradigm of compartmentalized specially treatment without a
      collaborative practice is ineffective for the chemical dependency and dual
      diagnosis population. Chemical dependency is not well understood as a disease,
      evidenced by barriers cited from the 2005 Survey on Drug Use and Health. Recovery
      from addiction and dual diagnosis logically demands an integrated and science
      based treatment approach with unified standards for care and improved educational
      standards for preparation of care providers. Consultation and collaboration with
      addiction and psychiatric specialists is needed to establish consistency in
      standards for treatment and holistic care, essential for comorbidity. Continued
      learning and research about the complexity of the addiction process and
      comorbidity will provide continued accurate information about the harmful effects
      of alcoholism and drug abuse which in turn will empower individuals to make
      informed choices and result in better treatment and social policies.

PMID- 22405710
TI  - Survivors of intimate partner violence: implications for nursing care.
AB  - As IPV increases in our society, hospitals need to prepare to best meet the needs
      of these individuals. Hospitals should have policies that encourage critical care
      nurses to consider abuse with the patients they serve. These policies need to
      ensure private, confidential interviewing of all patients and standardize the
      follow-up for any identified cases. There needs to be routine prompts in an
      assessment and history that clarify whether the person is in a violent situation.
      Nurses should understand more specifically the context of IPV and know the
      community resources available to survivors of this violence. Last, nurses need to
      recognize the physical, psychological, and emotional support they can give to
      these individuals. The acronym RADAR, developed by the Massachusetts Medical
      Society, succinctly represents the thought processes that need to occur with all
      domestic violence cases: R: Perform routine screening. A: Ask direct questions.
      D: Document findings. A: Assess patient (and children) safety. R: Review patient
      options and provide referrals. The ultimate aim for hospitals is to empower
      nurses to provide compassionate care for survivors and establish emotional
      climates conducive to IPV disclosure and subsequent care.

PMID- 22405711
TI  - Assessment of risk for in-hospital suicide and aggression in high-dependency care
      environments.
AB  - High-dependency environments are complex both from the standpoint of diversity of
      patient types and the nature of their functioning. Nurses manage this complexity
      at many different levels. Being attuned not only to the physical status of the
      patient but also the emotional/psychological status is paramount in maintaining a
      safe environment. Staff training and education is paramount in reducing risk.
      Institutions have a responsibility to provide resources to develop violence
      prevention programs.

PMID- 22405712
TI  - Incorporating the treatment of medical and psychiatric disorders in the critical
      care area.
AB  - Critical care areas are fast moving, often chaotic, and therefore confusing, even
      frightening, to patients attempting to understand what has happened to them. The
      nurse acts to mitigate these reactions by understanding the range of
      possibilities that can occur with patients, including potential psychiatric
      issues, and serving as patient advocate to ensure that appropriate treatment is
      initiated. Certainly there may be other psychiatric problems not described in the
      preceding text. The main possibilities are covered in this article. Assessing and
      acting early are tools the critical care nurse uses to meet patient needs and
      prevent behavioral problems that can interfere with life-preserving care.

PMID- 22405713
TI  - Collaborative partnerships between critical care and psychiatry.
AB  - The model of collaboration developed by D'Amour and associates can be used to
      analyze components of collaboration within organizations as shown in Fig. 1. The
      model covers both interprofessional and interorganizational components of
      collaboration. A strong supportive organizational infrastructure is the powerful
      force that sustains successful collaboration between critical care and
      psychiatry. Professionals' recognition that we have complementary, nonoverlapping
      clinical skills with recognizance of shared and overlapping populations is vital.
      The beauty of collaboration is the appreciation of the full value of each
      participant's unique contribution and diversity. When there are multiple
      opportunities for collaboration, everyone benefits, especially the critical care
      patient.

PMID- 22405714
TI  - How professional nurses working in hospital environments experience moral
      distress: a systematic review.
AB  - The experience of moral distress for professional nurses working in hospital
      environments causes a myriad of biological, psychological, and stress-related
      reactions. There is an institutional culpability in producing an environment
      where moral distress is experienced. This is particularly true when nurses feel
      the need to advocate for patients' well-being while coping with institutional
      constraints. The perception of patient pain and suffering as a result of medical
      decisions, which the nurse has little power to influence, contributes to the
      experience. Unequal power structures, prevalent in institutions, exacerbate the
      problem. Critical care nurses need to recognize moral distress and its adverse
      impact on providing optimal patient care. Critical care nurses should make a
      personal commitment that moral distress will not impact their nursing care and
      take a leadership role in their units to address this issue with their employing
      institution and develop strategies to lessen the impact of moral distress. These
      strategies should be based on the best available evidence such as this systematic
      review and other relevant appraised works.

PMID- 22405715
TI  - Critical care nursing and delirium management in the mentally ill client.
AB  - The critical care environment is an experience of stress for the patient and the
      practitioner. Turbulence can occur during the critical care course, which can
      cause exacerbation of chronic conditions. These exacerbations can lead to
      delirium and/or psychosis. Nursing professionals must be alert to changes in all
      conditions which increase morbidity and mortality in the critical care patient.
      Although critical care nurses may feel unable to care for the psychiatric needs
      of clients with a chronic mental disorder, implementing tools to aid in
      assessment will empower the nurses. Truly, the key to viewing all clients is
      wholly, rather than by diagnosis. Critical care nurses care for clients with many
      comorbidities and illnesses. Many conditions may be a new experience. Mental
      disorders should not be viewed as being out of the scope of the critical care
      nurse. On the contrary, mental disorders are chronic conditions, not unlike
      diabetes mellitus or congestive heart failure. What the critical care nurse needs
      is a knowledge base in order to feel more comfortable in caring for these
      clients. Knowledge is empowerment.

PMID- 22405716
TI  - Straddling the fence: ICU nurses advocating for hospice care.
AB  - A key factor in nurses' experiencing moral distress is their feeling of
      powerlessness to initiate discussions about code status, EOL issues, or patients'
      preferences. Moreover, nurses encounter physicians who give patients and their
      families a false picture of recovery or, worse, block EOL discussions from
      occurring. Since its release in 1995, the landmark study of almost 10,000
      patients in the Study to Understand Prognoses and Preferences for Outcomes and
      Risks of Treatments (SUPPORT) reported a widespread gap with physicians'
      discussions in honest prognosis and EOL issues. Since the SUPPORT report, other
      studies have validated patients' and their families' preference for realistic
      discussions of disease trajectory and life expectancy. Unfortunately, the
      phenomenon of physicians failing to discuss bad news or terminal disease
      trajectory persists. Moreover, with a burgeoning geriatric population, coupled
      with advances in medical treatments, a growing segment of chronically ill
      patients are admitted to the ICU. With these communication shortcomings, it
      becomes an essential element of practice for the ICU nurse to initiate
      discussions about healthcare goals, preferences, and choices. The ICU nurse must
      be integral in fostering those discussions, particularly in cases where the
      family asks if hospice should be considered. Nurses have a long history of
      patient advocacy, with both the American Nurses Association and the American
      Association of Critical-Care Nurses stating that nurses have a duty to educate
      and promote dialogue about patients' preferences, goals, and EOL issues. With
      these tenets in the forefront, the ICU nurse is an integral member of the
      healthcare team, working with patients and their families to distinguish between
      what can be done and what should be done. Too often, hospice is thought of as a
      last resort. Rather, it is a model of care that centers on the belief that each
      of us has the right to die pain free and with dignity, and that our families will
      receive the necessary support to allow us to do so. Despite the high satisfaction
      reported by decedents of hospice enrollees, 35% of all hospice patients die
      within 7 days of enrollment owing to late referrals. An ICU stay presents the
      perfect opportunity to weave EOL care planning into the fabric of everyday
      patient care. Clearly, the ICU setting cares for the very sickest patients, and
      knowing what patients and families desire must take precedence in all treatment
      decisions. The ICU nurse should be proficient in communication skills, using
      evidence-based communication related to functional status, performance scales,
      disease trajectory, and prognosis. ICU nurses recognize that not every patient
      survives their ICU stay; yet, for those patients who will not survive, every ICU
      nurse wants their patient to experience a "good death." Hospice and the
      palliative care are important aspects of our care continuum and should not be
      ignored until the last days or hours of a patient's life. Recognizing eligibility
      for hospice and its alignment with patient EOL preferences can result in optimal
      EOL care.

PMID- 22405717
TI  - Understanding the neurobiology, assessment, and treatment of substances of abuse
      and dependence: a guide for the critical care nurse.
AB  - What do I as a critical care nurse do? Nurses, by virtue of being trained in
      health promotion, and also because they interact with patients, families, and
      communities, have firsthand opportunities to play an active role in practicing
      primary prevention. To avoid the first occurrence of substance abuse, assess
      community need, assess facility needs, and identify potential risk. Identify the
      magnitude of the problem. Intervene early with the youth and at-risk populations.
      Refer patients and their families to mental health specialists. Provide education
      to patients, families, communities. To reduce occurrences of substance abuse,
      practicing secondary prevention requires prompt action in the earliest moments of
      recognizing a problem and directing patients to early intervention and
      rehabilitation. Screening your patients, providing brief education, and prompt
      referral constitutes early intervention. To retard the progress of the disease,
      practice tertiary prevention by providing education, counseling, and support to
      the afflicted in achieving and maintaining sobriety through medication compliance
      and rehabilitative group and counseling work. The goal of intervention in the
      lives of substance abusers is to stop drug use, avoid relapse, and sustain
      recovery. After years of research, NIDA has identified 13 fundamental principles
      to effective drug abuse treatment. 1. Addiction is a complex but treatable
      disease that affects brain function and behavior. 2. No single treatment is
      appropriate for everyone. 3. Treatment needs to be readily available. 4.
      Effective treatment attends to multiple needs of the individual, not just his or
      her drug abuse. 5. Remaining in treatment for an adequate period of time is
      critical. 6. Counseling--individual and/or group--and other behavioral therapies
      are the most commonly used forms of drug abuse treatment. 7. Medications are an
      important element of treatment for many patients, especially when combined with
      counseling and other behavioral therapies. 8. An individual's treatment and
      services plan must be assessed continually and modified as necessary to ensure it
      meets his or her changing needs. 9. Many drug-addicted individuals also have
      other mental disorders that need treatment. 10. Medically assisted detoxification
      in the first stage of addiction treatment and by itself does little to change
      long-term drug abuse. 11. Treatment does not need to be voluntary to be
      effective. 12. Drug use during treatment must be monitored continuously, because
      lapses during treatment do occur. 13. Treatment programs should assess patients
      for the presence of HIV/AIDS, hepatitis B and C, tuberculosis, and other
      infectious diseases, as well as provide targeted risk-reduction counseling to
      help patients modify or change behaviors that place them at risk of contracting
      or spreading infectious diseases. To truly impact this disease, there needs to be
      improvement in the identification of risk factors and early identification and
      early intervention with children and adolescents. The future of neuroscience is
      in objective brain scans and genetic testing. Out of these approaches can come
      more objective measures of addiction and dependence using brain scans and genetic
      testing. These measures would potentially allow for the development of vaccines
      for specific drugs of abuse and dependence, as well as increasingly selective and
      effective pharmacologic approaches for treatment and a new consensus on standard
      of care for substance dependence.

PMID- 22405718
TI  - Acute delirium: differentiation and care.
AB  - The health care costs for patients with delirium were estimated to be more than
      double the costs for patients without delirium and potentially exceeded the costs
      for falls, diabetes mellitus, and hip fractures; yet the fluctuating nature of
      the condition makes it a difficult condition for health professionals to
      recognize and treat. The key, then, is in recognition and prevention.

PMID- 22405719
TI  - The stigma of a psychiatric diagnosis: prevalence, implications and nursing
      interventions in clinical care settings.
AB  - The stigma associated with psychiatric and substance abuse disorders is a
      formidable barrier to the achievement of health and well-being for persons who
      carry such a diagnosis or who exhibit symptoms. Attitudes of nurses and treatment
      providers toward patients with comorbid psychiatric and substance abuse disorders
      can be influenced by stigma, which can have a negative impact on the therapeutic
      process and development of trust necessary to support good patient outcomes.
      Understanding the interrelated components of stigma, including labeling,
      stereotypes, and discrimination, can help nurses to reduce its impact in clinical
      care settings to improve the care experience for patients and nurses.
      Implementing interventions based on the core values of the nurse-patient
      relationship to enhance understanding, mutual trust, and acceptance of
      differences can contribute to improved communication and patient assessments in
      an effort to improve patient outcomes.

PMID- 22405720
TI  - Critical care of patients with mental health issues. Preface.

PMID- 22405721
TI  - Prevalence of latent alpha-herpesviruses in Thoroughbred racing horses.
AB  - The objective of this study was to detect and characterize latent equine herpes
      virus (EHV)-1 and -4 from the submandibular (SMLN) and bronchial lymph (BLN)
      nodes, as well as from the trigeminal ganglia (TG) of 70 racing Thoroughbred
      horses submitted for necropsy following sustaining serious musculoskeletal
      injuries while racing. A combination of nucleic acid precipitation and pre
      amplification steps was used to increase analytical sensitivity. Tissues were
      deemed positive for latent EHV-1 and/or -4 infection when found PCR positive for
      the corresponding glycoprotein B (gB) gene in the absence of detectable late
      structural protein gene (gB gene) mRNA. The EHV-1 genotype was also determined
      using a discriminatory real-time PCR assay targeting the DNA polymerase gene (ORF
      30). Eighteen (25.7%) and 58 (82.8%) horses were PCR positive for the gB gene of
      EHV-1 and -4, respectively, in at least one of the three tissues sampled. Twelve
      horses were dually infected with EHV-1 and -4, two carried a latent neurotropic
      strain of EHV-1, six carried a non-neurotropic genotype of EHV-1 and 10 were
      dually infected with neurotropic and non-neurotropic EHV-1. The distribution of
      latent EHV-1 and -4 infection varied in the samples, with the TG found to be most
      commonly infected. Overall, non-neurotropic strains were more frequently detected
      than neurotropic strains, supporting the general consensus that non-neurotropic
      strains are more prevalent in horse populations, and hence the uncommon
      occurrence of equine herpes myeloencephalopathy.

PMID- 22405722
TI  - Detection of early effects of a single herbicide (diuron) and a mix of herbicides
      and pharmaceuticals (diuron, isoproturon, ibuprofen) on immunological parameters
      of Pacific oyster (Crassostrea gigas) spat.
AB  - In the context of massive summer mortality events of the Pacific oyster
      Crassostrea gigas, the aim of this study was to investigate the early effects on
      genes, enzymes and haemocyte parameters implicated in immune defence mechanisms
      in C. gigas oysters exposed to a potentially hostile environment, i.e. to an
      herbicide alone or within a mixture. Following 2 h of exposure to the herbicide
      diuron at 1 MUg L(-1), the repression of different genes implicated in immune
      defence mechanisms in the haemocytes and the inhibition of enzyme activities,
      such as laccase-type phenoloxidase (PO) in the plasma, were observed. The
      inhibition of superoxide dismutase (SOD) activity in the plasma was also observed
      after 6 and 24 h of exposure. In the mixture with the herbicides diuron and
      isoproturon, and the pharmaceutical ibuprofen, catecholase-type PO activity in
      the plasma and the percentage of phagocytosis in the haemocytes were reduced
      after 6 h of exposure. Our results showed that early effects on molecular,
      biochemical and cellular parameters can be detected in the presence of diuron
      alone or within a mixture, giving an insight of its potential effect in
      situations that can be found in natural environments, i.e. relatively high
      concentrations for short periods of time.

PMID- 22405723
TI  - Analysis of mixed halogenated dibenzo-p-dioxins and dibenzofurans (PXDD/PXDFs) in
      soil by gas chromatography tandem mass spectrometry (GC-MS/MS).
AB  - Mixed halogenated dibenzo-p-dioxins and dibenzofurans (PXDD/PXDFs, X=Br, Cl) are
      formed through combustion processes, and may be more toxic than their
      corresponding chlorinated and brominated analogues. With 4600 potential
      congeners, limited analytical standards, and complex environmental matrices,
      PXDD/PXDFs present a significant analytical challenge. Gas chromatography tandem
      mass spectrometry (GC-MS/MS) offers both selectivity and sensitivity through
      multiple reaction monitoring of unique transitions in a novel approach to
      PXDD/PXDF congener identification. Method validation was performed through
      analysis of soil samples obtained from a recycling plant fire. Of the PXDD/PXDFs
      examined, monobromo-dichlorodibenzofuran was the most prevalent, ranging in
      concentration from 8.6ngg(-1) to 180ngg(-1). Dibromo-dichlorodibenzo-p-dioxin, a
      compound of toxicological concern, ranged from 0.41ngg(-1) to 10ngg(-1).
      Concentrations of PXDD/PXDFs were between 6% and 10% that of the corresponding
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs), with the
      exception of dibromo-dichlorodibenzo-p-dioxin concentrations, which were 36% that
      of tetrachlorodibenzo-p-dioxins. Higher levels of polybrominated PXDD/PXDFs may
      indicate a significant bromine source was present during combustion.

PMID- 22405724
TI  - Evaluation of two new surrogate indices including parameters not using insulin to
      assess insulin sensitivity/resistance in non-diabetic postmenopausal women: a
      MONET group study.
AB  - AIM: The study evaluated and compared, with other surrogate indices of insulin
      sensitivity/resistance (IS/R), the relevance of the TyG index, a product of
      fasting glucose and triglyceride (TG) levels, and the EGIR index, which includes
      TG, high-density lipoprotein cholesterol (HDL-c) and waist circumference in its
      formula to estimate IS/R, in non-diabetic postmenopausal women. METHODS: A
      secondary analysis was performed using the baseline data for 163 non-diabetic
      postmenopausal women from the Montreal-Ottawa New Emerging Team (MONET)
      population database. The subjects participated in hyperinsulinaemic-euglycaemic
      (HIEG) clamp and oral glucose tolerance (OGTT) tests. Correlations and
      comparisons between surrogate indices were performed in addition to inter-rater
      agreement tests. The optimal value of surrogate indices for diagnosis of IS/R was
      established on a receiver operating characteristic (ROC) scatter plot. RESULTS: A
      significant correlation was found between the HIEG clamp and all IS/R surrogate
      indices tested [r=-0.370 (TyG index) to 0.608 (SIisOGTT index); P<0.001]. On ROC
      curve analysis, a higher AUROC was found for SIisOGTT (0.791) than for TyG and
      EGIR (0.706 and 0.675, respectively; P=0.07 and P<0.05, respectively).
      CONCLUSION: The TyG and EGIR IS/R indices were only relatively modestly related
      to the HIEG clamp. In contrast, both fasting- and OGTT-derived IS/R surrogate
      indices, which include insulin values in their formulae, appeared to be more
      accurate in estimating IS/R in our study population. Thus, the TyG and EGIR IS/R
      indices need to be tested and validated more extensively in different populations
      before being put to large-scale clinical use.

PMID- 22405726
TI  - Cardiovascular responses evoked by activation or blockade of GABA(A) receptors in
      the hypothalamic PVN are attenuated in transgenic rats with low brain
      angiotensinogen.
AB  - Previous evidence indicates that a balance between inhibitory gabaergic and
      excitatory angiotensinergic factors in the PVN is important for cardiovascular
      control. We investigated the cardiovascular response evoked from activation or
      blockade of GABA(A) receptors in the paraventricular nucleus (PVN), in transgenic
      rats with low brain angiotensinogen [TGR(ASrAOGEN)]. Brain Ang II and Ang-(1-7)
      levels were also determined. In functional experiments, TGR(ASrAOGEN) and Sprague
      Dawley rats (SD, control) were anesthetized with urethane and blood pressure
      (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded.
      Brain Ang II and Ang-(1-7) levels were largely reduced in TGR(ASrAOGEN) compared
      with SD rats. Inhibition of PVN neurons with the GABA(A) agonist, muscimol (1
      nmol/100 nL), resulted in an attenuated fall in all cardiovascular variables in
      TGR(ASrAOGEN) compared with SD rats. This difference was particularly pronounced
      in HR (TGR Mus -23+/-6 bpm vs. -77+/-9 bpm SD Mus; P<0.05) and RSNA (TGR -3+/-10%
      vs.-29+/-8% SD; P<0.05). Furthermore, the sympathetic response evoked by blockade
      of GABA(A) receptors in the PVN of TGR(ASrAOGEN) was also largely suppressed. The
      present data indicate that the sympathetic outflow mediated by PVN neurons under
      basal conditions is suppressed in TGR(ASrAOGEN) rats corroborating the functional
      significance of brain angiotensin production in the central regulation of
      sympathetic output to the cardiovascular system.

PMID- 22405725
TI  - TDP-43 aggregation in neurodegeneration: are stress granules the key?
AB  - The RNA-binding protein TDP-43 is strongly linked to neurodegeneration. Not only
      are mutations in the gene encoding TDP-43 associated with ALS and FTLD, but this
      protein is also a major constituent of pathological intracellular inclusions in
      these diseases. Recent studies have significantly expanded our understanding of
      TDP-43 physiology. TDP-43 is now known to play important roles in neuronal RNA
      metabolism. It binds to and regulates the splicing and stability of numerous RNAs
      encoding proteins involved in neuronal development, synaptic function and
      neurodegeneration. Thus, a loss of these essential functions is an attractive
      hypothesis regarding the role of TDP-43 in neurodegeneration. Moreover, TDP-43 is
      an aggregation-prone protein and, given the role of toxic protein aggregates in
      neurodegeneration, a toxic gain-of-function mechanism is another rational
      hypothesis. Importantly, ALS related mutations modulate the propensity of TDP-43
      to aggregate in cell culture. Several recent studies have documented that
      cytoplasmic TDP-43 aggregates co-localize with stress granule markers. Stress
      granules are cytoplasmic inclusions that repress translation of a subset of RNAs
      in times of cellular stress, and several proteins implicated in neurodegeneration
      (i.e. Ataxin-2 and SMN) interact with stress granules. Thus, understanding the
      interplay between TDP-43 aggregation, stress granules and the effect of ALS
      associated TDP-43 mutations may be the key to understanding the role of TDP-43 in
      neurodegeneration. We propose two models of TDP-43 aggregate formation. The
      "independent model" stipulates that TDP-43 aggregation is independent of stress
      granule formation, in contrast to the "precursor model" which presents the idea
      that stress granule formation contributes to a TDP-43 aggregate "seed" and that
      chronic stress leads to concentration-dependent TDP-43 aggregation. This article
      is part of a Special Issue entitled: RNA-Binding Proteins.

PMID- 22405727
TI  - Consequences of pilocarpine-induced status epilepticus in immunodeficient mice.
AB  - Systemic injection of pilocarpine in rodents induces status epilepticus (SE) and
      reproduces the main characteristics of temporal lobe epilepsy (TLE). Different
      mechanisms are activated by SE contributing to cell death and immune system
      activation. We used BALB/c nude mice, a mutant that is severely
      immunocompromised, to characterize seizure pattern, neurochemical changes, cell
      death and c-Fos activation secondarily to pilocarpine-induced SE. The behavioral
      seizures were less severe in BALB/c nude than in BALB/c wild type mice. However,
      nude mice presented more tonic-clonic episodes and higher mortality rate during
      SE. The c-Fos expression was most prominent in the caudate-putamen, CA3 (p<0.05),
      dentate gyrus, entorhinal cortex (p<0.001), basolateral nucleus of amygdala
      (p<0.01) and piriform cortex (p<0.05) of BALB/c nude mice than of BALB/c.
      Besides, nude mice subjected to SE presented high number of Fluorojade-B (FJB)
      stained cells in the piriform cortex, amygdala (p<0.05) and hilus (p<0.001) in
      comparison with BALB/c mice. A significant increase in the level of glutamate and
      GABA was found in the hippocampus and cortex of BALB/c mice presenting SE in
      comparison to controls. However, the level of glutamate was higher in the brains
      of BALB nude mice than in the brains of BALB/c wild type mice, while the levels
      of GABA were unchanged. These results indicate that the brains of immunodeficient
      nude mice are more vulnerable to the deleterious effects of pilocarpine-induced
      SE as they present intense activation, increased glutamate levels and more cell
      death.

PMID- 22405730
TI  - Multiple endocrine carcinomas of the ileum.

PMID- 22405728
TI  - RNA-binding proteins in microsatellite expansion disorders: mediators of RNA
      toxicity.
AB  - Although protein-mediated toxicity in neurological disease has been extensively
      characterized, RNA-mediated toxicity is an emerging mechanism of pathogenesis. In
      microsatellite expansion disorders, expansion of repeated sequences in noncoding
      regions gives rise to RNA that produces a toxic gain of function, while
      expansions in coding regions can disrupt protein function as well as produce
      toxic RNA. The toxic RNA typically aggregates into nuclear foci and contributes
      to disease pathogenesis. In many cases, toxicity of the RNA is caused by the
      disrupted functions of RNA-binding proteins. We will discuss evidence for RNA
      mediated toxicity in microsatellite expansion disorders. Different microsatellite
      expansion disorders are linked with alterations in the same as well as disease
      specific RNA-binding proteins. Recent studies have shown that microsatellite
      expansions can encode multiple repeat-containing toxic RNAs through bidirectional
      transcription and protein species through repeat-associated non-ATG translation.
      We will discuss approaches that have characterized the toxic contributions of
      these various factors.

PMID- 22405729
TI  - White matter integrity, language, and childhood onset schizophrenia.
AB  - BACKGROUND: The heterogeneity of symptoms and cognitive deficits in schizophrenia
      can be explained by abnormal connectivity between brain regions. Childhood-onset
      schizophrenia (COS) is a particularly severe form of schizophrenia, with an onset
      during a key time period for both cerebral pruning and myelination. METHODS:
      Diffusion tensor images were acquired from 18 children and adolescents with COS
      and 25 controls. The COS group was divided into two sub-groups-one with
      linguistic impairment (LI) and the other without (NLI). The fractional anisotropy
      (FA), axial (AD), and radial diffusivity (RD) data from the two COS sub-groups
      were compared to each other and to the controls using tract-based spatial
      statistics (TBSS) analyses, which is a voxel-based method used to identify
      regions of white matter abnormalities. RESULTS: TBSS identified several regions
      in the left hemisphere where the LI group had increased AD and RD relative to the
      NLI and the control groups. These areas primarily localized to linguistic tracts:
      left superior longitudinal fasciculus and left inferior longitudinal
      fasciculus/inferior fronto-occipital fasciculus. Regions of increased RD
      overlapped regions of increased AD, with the former showing more pronounced
      effects. CONCLUSIONS: Studies of adult-onset schizophrenia typically identify
      areas of higher RD but unchanged AD; however, normal development studies have
      shown that while RD decreases are pronounced over this age range, smaller
      decreases in AD can also be detected. The observed increases in both RD and AD
      suggest that developmental disturbances affecting the structural connectivity of
      these pathways are more severe in COS accompanied by severe linguistic
      impairments.

PMID- 22405731
TI  - Lowered frequency and impaired modulation of gamma band oscillations in a bimodal
      attention task are associated with reduced critical flicker frequency.
AB  - Visual attention is associated with occipital gamma band activity. While gamma
      band power can be modulated by attention, the frequency of gamma band activity is
      known to decrease with age. The present study tested the hypothesis that reduced
      visual attention is associated with a change in induced gamma band activity. To
      this end, 26 patients with liver cirrhosis and 8 healthy controls were tested. A
      subset of patients showed symptoms of hepatic encephalopathy (HE), a frequent
      neuropsychiatric complication in liver disease, which comprises a gradual
      increase of cognitive dysfunction including attention deficits. All participants
      completed a behavioral task requiring shifts of attention between simultaneously
      presented visual and auditory stimuli. Brain activity was recorded using
      magnetoencephalography (MEG). The individual critical flicker frequency (CFF) was
      assessed as it is known to reliably reflect the severity of HE. Results showed
      correlations of behavioral data and HE severity, as indexed by CFF. Individual
      visual gamma band peak frequencies correlated positively with the CFF (r=0.41).
      Only participants with normal, but not with pathological CFF values showed a
      modulation of gamma band power with attention. The present results suggest that
      CFF and attentional performance are related. Moreover, a tight relation between
      the CFF and occipital gamma band activity both in frequency and power is shown.
      Thus, the present study provides evidence that a reduced CFF in HE, a disease
      associated with attention deficits, is closely linked to a slowing of gamma band
      activity and impaired modulation of gamma band power in a bimodal attention task.

PMID- 22405732
TI  - Nonverbal sound processing in semantic dementia: a functional MRI study.
AB  - Semantic dementia (SD) is a unique neurodegenerative syndrome accompanied by
      relatively selective loss of the meaning of objects and concepts. The brain
      mechanisms that underpin the syndrome have not been defined: a better
      understanding of these mechanisms would inform our understanding of both the
      organisation of the human semantic system and its vulnerability to
      neurodegenerative disease. In this fMRI study, we investigated brain correlates
      of sensory object processing in nine patients with SD compared with healthy
      control subjects, using the paradigm of nonverbal sound. Compared with healthy
      controls, patients with SD showed differential activation of cortical areas
      surrounding the superior temporal sulcus, both for perceptual processing of
      spectrotemporally complex but meaningless sounds and for semantic processing of
      environmental sound category (animal sounds versus tool sounds). Our findings
      suggest that defective processing of sound objects in SD spans pre-semantic
      perceptual processing and semantic category formation. This disease model
      illustrates that antero-lateral temporal cortical mechanisms are critical for
      representing and differentiating sound categories. The breakdown of these
      mechanisms constitutes a network-level functional signature of this
      neurodegenerative disease.

PMID- 22405733
TI  - A clustering-based method to detect functional connectivity differences.
AB  - Recently, resting-state functional magnetic resonance imaging (R-fMRI) has
      emerged as a powerful tool for investigating functional brain organization
      changes in a variety of neurological and psychiatric disorders. However, the
      current techniques may need further development to better define the reference
      brain networks for quantifying the functional connectivity differences between
      normal and diseased subject groups. In this study, we introduced a new clustering
      based method that can clearly define the reference clusters. By employing group
      difference information to guide the clustering, the voxels within the reference
      clusters will have homogeneous functional connectivity changes above predefined
      levels. This method identified functional clusters that were significantly
      different between the amnestic mild cognitively impaired (aMCI) and age-matched
      cognitively normal (CN) subjects. The results indicated that the distribution of
      the clusters and their functionally disconnected regions resembled the altered
      memory network regions previously identified in task fMRI studies. In conclusion,
      the new clustering method provides an advanced approach for studying functional
      brain organization changes associated with brain diseases.

PMID- 22405734
TI  - Multitargeted anti-angiogenic agents and NSCLC: clinical update and future
      directions.
AB  - Increasing understanding of the molecular abnormalities driving cell growth and
      proliferation has resulted in extensive research into molecularly targeted
      therapies. Angiogenesis is an appealing target for the treatment of non small
      cell lung cancer (NSCLC). Bevacizumab, a monoclonal antibody against circulating
      vascular endothelial growth factor (VEGF), is already approved for the treatment
      of NSCLC. Many other anti-angiogenic agents under development form the focus of
      this review. A variety of agents, including sorafenib, sunitinib, cediranib,
      axitinib, motesanib, linifinib and brivanib inhibit VEGF in addition to either
      platelet derived growth factor (PDGF), or fibroblast derived growth factor (FGF).
      To date, none of these agents in combination with chemotherapy have resulted in
      improvements in overall survival for patients with advanced NSCLC. Triple
      angiokinase inhibitors, which inhibit VEGF, PDGF and FGF, have potential to
      improve the therapeutic outcomes for patients with NSCLC. However, there is a
      need for identification of appropriate biomarkers to improve patient selection
      and identify those patients benefiting from anti-angiogenesis therapy.

PMID- 22405735
TI  - Comparison of laparoscopic adjustable gastric banding (LAGB) with other bariatric
      procedures; a systematic review of the randomised controlled trials.
AB  - BACKGROUND: Bariatric surgery can provide efficient weight loss and improvement
      in obesity-related co-morbidities in adults. Laparoscopic adjustable gastric
      banding (LAGB) comprised 30.3% of all bariatric procedures between 2009 and 2010
      in the UK. This review evaluates the level 1 evidence for change in co
      morbidities, quality of life (QoL) and weight provided by LAGB compared with
      other bariatric procedures. METHOD: Systematic literature search of MEDLINE,
      EMBASE and CENTRAL (1988 to May 2011) was performed. Only randomised controlled
      trials (RCTs) were included. Studies with non-surgical comparators, open gastric
      banding procedures or adolescent participants were excluded. Primary outcome was
      change in co-morbidities. Secondary outcomes included QoL, weight loss,
      complications, operation time and length of stay. RESULTS: Five RCTs met the
      inclusion criteria. Vertical banded gastroplasty, sleeve gastrectomy and gastric
      bypass were compared to LAGB. Co-morbidities were reported in two studies and QoL
      in one. LAGB was comparable to other procedures for both of these outcomes. All
      five trials showed LABG to be effective in weight loss, however all comparative
      procedures resulted in greater weight loss. Operative time and length of hospital
      stay were significantly shorter with LAGB. Short-term complications were found to
      be consistently lower in the LAGB group. Evidence was divided with respect to
      long-term complications. CONCLUSION: Co-morbidities and QoL are poorly reported
      and showed no difference between LAGB and other bariatric procedures. Evidence
      suggests that LAGB is not the most effective surgical procedure to reduce weight.
      LAGB is associated with lower early complications and shorter operative time and
      length of stay, and therefore may be preferable to patients.

PMID- 22405737
TI  - Deep Brain Stimulation device removal after scar picking behaviors in a patient
      with treatment-resistant obsessive compulsive disorder.

PMID- 22405736
TI  - Algorithmic management of pediatric acute mastoiditis.
AB  - OBJECTIVE: Today, no uniformly accepted diagnostic and therapeutic criteria have
      been established for the management of pediatric acute mastoiditis. The aim of
      this study is determine the efficacy and safety of an algorithmic approach for
      treating pediatric acute mastoiditis. METHODS: The medical records of all
      children (n=167) with a diagnosis of AM admitted in our center during the period
      2002-2010 were retrospectively studied. Data concerning medical history,
      symptomatology, laboratory and imaging findings, presence of complications,
      treatment methods and final outcomes were reviewed and analyzed. Parenteral
      antibiotics and myringotomy were applied to all children on the day of admission.
      Initial surgical approach also included drainage or simple mastoidectomy for
      subperiosteal abscesses and simple mastoidectomy for children suffering from
      intracranial complications. Finally, simple mastoidectomy was performed as a
      second line treatment in children showing poor response to the initial
      conservative approach. RESULTS: All children were cured after a mean
      hospitalization of 9.8 days. The rate of intracranial complications at admission
      was 6.5% and the overall rate of the use of mastoidectomy 42%. Following the
      presented treatment scheme in all cases, no child developed additional
      complications while in-hospital and under treatment or after discharge.
      CONCLUSIONS: Although simple mastoidectomy represents the most reliable and
      effective surgical method to treat acute mastoiditis, a more conservative
      approach consisting of adequate parenteral antibiotic coverage and myringotomy
      can be safely adopted for all children suffering from uncomplicated acute
      mastoiditis. Non-responsive cases should undergo simple mastoidectomy within 3-5
      days in order to avoid further in-hospital acquired complications. Simple
      mastoidectomy should also be performed in every case of unsuccessful
      subperiosteal abscess drainage or presence of intracranial complications.

PMID- 22405738
TI  - Quadri-pulse stimulation induces stimulation frequency dependent cortical
      hemoglobin concentration changes within the ipsilateral motor cortical network.
AB  - BACKGROUND: Imaging studies investigating repetitive transcranial magnetic
      stimulation (rTMS) mediated hemodynamic consequences revealed inconsistent
      results, mainly due to differences in rTMS parameters and technical difficulties
      with simultaneous recordings during rTMS. OBJECTIVE/HYPOTHESIS: Quadri-pulse rTMS
      (QPS) induces bidirectional long-term plasticity of the human primary motor
      cortex (M1). To evaluate its on-line effects, near infrared spectroscopy (NIRS)
      recordings were performed during QPS. We hypothesized that on-line effects during
      QPS are different from long-term aftereffects. METHODS: Using a novel TMS - on
      line multi-channel NIRS setup we recorded hemoglobin concentration [Hb] changes
      at the stimulated M1 and adjacent sensory-motor areas during QPS protocols
      inducing oppositely directed aftereffects (QPS-5: interstimulus interval (ISI) 5
      ms, potentiation; QPS-50: ISI 50 ms, depression). In two experiments we studied
      NIRS changes during either single or repeated QPS bursts. RESULTS: The repetitive
      QPS-5 bursts significantly decreased oxyhemoglobin concentration ([oxy-Hb]) in
      the ipsilateral M1. A single QPS-5 burst decreased [oxy-Hb] in the M1 and
      premotor cortex. QPS-50 induced no significant NIRS changes at any sites.
      CONCLUSIONS: QPS can significantly alter cortical hemodynamics depending on the
      stimulation frequency. While bidirectional long-term aftereffects of QPS reflect
      synaptic efficacy changes, unidirectional on-line effects during QPS may
      represent pure electrophysiological property changes within the cell membrane or
      synapse. Since neuronal postexcitatory inhibitory postsynaptic potentials
      typically peak within the first 10-20 ms, only pulses delivered at higher
      frequencies may lead to summation of the inhibitory effects, resulting in [oxy
      Hb] decrease only after QPS-5. Our new TMS-NIRS setup may be valuable to
      investigate TMS induced neurovascular coupling mechanisms in humans.

PMID- 22405739
TI  - Deep brain stimulation of the forniceal area enhances memory functions in
      experimental dementia: the role of stimulation parameters.
AB  - Deep brain stimulation (DBS) is currently being evaluated as a potential therapy
      in improving memory functions in Alzheimer's disease. The target for DBS and the
      stimulation parameters to be used are unknown. Here, we implanted bilateral
      electrodes in the vicinity of the fornix, a key element of the memory circuitry,
      and applied DBS with different stimulation frequencies and amplitudes in an
      experimental model of dementia. Rats received scopolamine, a muscarinic
      acetylcholine receptor antagonist, to mimic memory impairment. Rats were then
      tested in the object location task with the following conditions: (i) with
      attachment of stimulation cable (off stimulation), and (ii) with DBS at various
      amplitudes (50 MUA, 100 MUA and 200 MUA), 100 MUs pulse width and 100 Hz or 10 Hz
      stimulation frequency. DBS reversed the memory impairing effects of scopolamine
      when compared to sham rats. We found that the fornix is not sensitive to the
      frequency of stimulation, but rather to current levels. With the most optimal
      stimulation parameter, we found no side-effects on anxiety levels and general
      motor activity. These findings identify the fornix as a key region in controlling
      spatial memory functions. DBS of this region, using tailored stimulation
      parameters, has the potential to improve memory functions in conditions
      characterised by memory impairment.

PMID- 22405740
TI  - Predict the outcome of depression after rTMS using neuroimaging: issue of
      response or non-response?

PMID- 22405741
TI  - Changes in psychological functioning signaling antidepressant response onset to
      transcranial magnetic stimulation.

PMID- 22405742
TI  - Vagus nerve stimulation ameliorated deficits in one-way active avoidance learning
      and stimulated hippocampal neurogenesis in bulbectomized rats.
AB  - BACKGROUND: Vagus nerve stimulation (VNS) has been introduced as a therapeutic
      option for treatment-resistant depression. The neural and chemical mechanisms
      responsible for the effects of VNS are largely unclear. METHODS: Bilateral
      removal of the olfactory bulbs (OBX) is a validated animal model in depression
      research. We studied the effects of vagus nerve stimulation (VNS) on disturbed
      one-way active avoidance learning and neurogenesis in the hippocampal dentate
      gyrus of rats. RESULTS: After a stimulation period of 3 weeks, OBX rats acquired
      the learning task as controls. In addition, the OBX-related decrease of neuronal
      differentiated BrdU positive cells in the dentate gyrus was prevented by VNS.
      CONCLUSIONS: This suggests that chronic VNS and changes in hippocampal
      neurogenesis induced by VNS may also account for the amelioration of behavioral
      deficits in OBX rats. To the best of our knowledge, this is the first report on
      the restorative effects of VNS on behavioral function in an animal model of
      depression that can be compared with the effects of antidepressants.

PMID- 22405743
TI  - Repetitive transcranial magnetic stimulation (rTMS) noise: a relevance for
      tinnitus treatment?

PMID- 22405744
TI  - Direct stereotactic targeting of the ventrointermediate nucleus of the thalamus
      based on anatomic 1.5-T MRI mapping with a white matter attenuated inversion
      recovery (WAIR) sequence.
AB  - BACKGROUND: The ventrointermediate nucleus (Vim) of the thalamus is still
      considered "invisible" on current magnetic resonance imaging (MRI), requiring
      indirect methods based on stereotactic atlases for estimation of its location.
      Direct visualization of Vim is desirable to improve targeting. OBJECTIVE: To
      evaluate the ability of Inversion-Recovery 1.5-T MR images to produce high
      resolution, anatomical depiction of the thalamus suitable for direct Vim
      targeting. METHODS: Twenty patients with essential tremor or tremor associated
      with Parkinson's disease received Vim deep brain stimulation (DBS). Fahn-Tolosa
      Marin and Unified Parkinson's Disease Rating Scale (UPDRS) tremor scores were
      assessed pre- and postoperatively. Preoperative stereotactic 1.5-T MR images of
      the thalamus were acquired using a White Matter Attenuated Inversion Recovery
      (WAIR) sequence. Thalamic nuclei were manually contoured on the basis of
      spontaneous MRI contrasts; labeling relied on 3D identification from stereotactic
      books and in-house ex vivo 4.7-T microscopic MRI atlas. Vim was then directly
      probed for electrophysiological confirmation and determination of the optimal
      site for electrode placement. RESULTS: The shape, spatial orientation, and signal
      contrast of Vim as depicted on our WAIR images were similar to those observed on
      the Schaltenbrand and Bailey atlas, as well as in our high-field MRI atlas. These
      images were successfully used for pure direct Vim targeting: at the last follow
      up (median = 46.3 months), the average tremor score improved from 3.80
      preoperatively to 0.50 postoperatively (on stimulation; P < 0.01). CONCLUSION:
      1.5-T MRI with WAIR sequence provides high-quality images of Vim suitable in DBS
      surgery, for accurate preoperative planning, direct targeting and anatomic
      analysis.

PMID- 22405745
TI  - The fade-in--short stimulation--fade out approach to sham tDCS--reliable at 1 mA
      for naive and experienced subjects, but not investigators.
AB  - OBJECTIVE: Slowly ramping down initial current intensity after a minimal interval
      of stimulation is the de facto standard for sham stimulation in transcranial
      electrical stimulation research. The aim of this study is to further investigate
      the effectiveness of this method of blinding. METHODS: We have investigated the
      time course of the cutaneous perception during 10 min of anodal, cathodal, and
      sham transcranial direct current stimulation, probing the perceived strength and
      site of the perceived sensation. We have also utilized post-stimulation
      assessment and measurements of sleepiness prior to and after the intervention.
      Previous exposure to tDCS has also been taken into account: the experiment has
      been repeated in naive and experienced subject groups, and a group consisting of
      investigators who use tDCS as a research tool. RESULTS: Although we have observed
      a general reduction in the perceived strength of the stimulation with time, we
      have not found the complete disappearance of the cutaneous perception during
      either the verum or the sham conditions. Experienced subjects were more likely to
      be able to differentiate between trials with stimulation and non-stimulation
      trials and to correctly identify sham and verum stimulation conditions.
      CONCLUSION: When taking only naive and experienced subjects into account, there
      was no significant difference between the strength of the perceived stimulation
      in the verum and sham conditions. The fade-in - short stimulation - fade-out sham
      stimulation can be indistinguishable from verum stimulation, but not because it
      mimics the disappearance of the cutaneous sensations associated with the verum
      stimulation, but because these sensations persist also in the sham stimulation.
      The significance of this finding with potential confounding factors and
      limitations are discussed.

PMID- 22405746
TI  - Structural characterization of hemicelluloses fractionated by graded ethanol
      precipitation from Pinus yunnanensis.
AB  - Fractionation of hemicelluloses from delignified Pinus yunnanensis was carried
      out with KOH/H(3)BO(3) solution followed by graded precipitation in 15%, 60%, and
      90% (v/v) ethanol solutions, respectively. Chemical compositions, physicochemical
      properties, and structures of the precipitated hemicellulosic fractions were
      elucidated by a combination of sugar analysis, GPC, FT-IR, and (1)H, (13)C and 2D
      HSQC NMR spectroscopy. Sugar analysis showed that the hemicellulosic fraction
      precipitated by 15% ethanol solution (H(1)) had a predominance of xylose
      (58.52%), while mannose was the major sugar component in the hemicellulosic
      fractions precipitated by 60% (H(2)) and 90% (H(3)) ethanol solutions. GPC
      results revealed that the hemicelluloses precipitated by low concentration of
      ethanol solutions had higher weight-average molecular mass (50,090-79,840 g/mol)
      than those obtained in the high concentration of ethanol solutions (16,500
      g/mol). The fraction precipitated by 60% ethanol solution (H(2)) was composed of
      D-galactose, D-glucose and D-mannose in a ratio of approximately 1:1:3.5.
      Structural determination indicated that the hemicellulosic fraction (H(2)) had a
      main structure of (1->4)-linked beta-glucomannans backbone with (1->6)-linked
      alpha-D-galactose as a side chain attached to C-6 of mannose units. In addition,
      this fraction also contained minor amounts of xylans.

PMID- 22405747
TI  - Pain management in heroin and cocaine users.
AB  - Drug addicts often seek medical help for pain. Numerous fears and beliefs may
      hinder the recognition, evaluation, and management of pain in addicts.
      Nevertheless, the same fundamental principles apply to these patients as to other
      patients in terms of pain evaluation, analgesic selection, and dosage adjustment.
      Clarity of the medical prescription is crucial. Specific points that require
      attention in addicts include the effects of the abused drugs on the nociceptive
      system, the nature and amount of abused drugs, concomitant nondrug addictions, co
      morbidities, and the nature of the pain symptoms. Also crucial is differentiating
      current abusers from former abusers and from abusers taking replacement therapy,
      as different management strategies are required in these three situations.
      Detailed information on the history of drug abuse is necessary to avoid unwanted
      events (e.g., overdosing or withdrawal syndrome) or an exacerbation of the
      addictive behaviors. In practice, hospital admission should be avoided to the
      extent possible. The use of strong opioids should be kept to a minimum (although
      this important rule may be difficult to follow, for instance in surgical
      emergencies). The best route of administration and galenic formulation vary with
      each individual situation but, in general, intravenous administration of strong
      opioids is highly undesirable. A treatment contract established with the patient
      is crucial and must indicate the nature of the drug or replacement agent used and
      the treatments given for pain control.

PMID- 22405748
TI  - An outbreak of human parainfluenza virus 3 infection in an outpatient
      hematopoietic stem cell transplantation clinic.
AB  - BACKGROUND: Parainfluenza viruses cause respiratory tract infections in adults
      and children, with peak activity during the spring and summer months. Human
      parainfluenza virus type 3 (hPIV-3) can contribute to significant morbidity and
      mortality in patients undergoing hematopoietic stem cell transplantation (HSCT).
      METHODS: Automated surveillance software was used to identify an hPIV-3 outbreak
      in an HSCT clinic. Active surveillance for respiratory illness and infection
      control measures were instituted. A retrospective molecular investigation of
      outbreak viral strains was performed by direct sequencing. RESULTS: Twelve of 196
      HSCT recipients attending the clinic during the outbreak period had hPIV-3; one
      of these patients died. Sequencing demonstrated highly related strains in 9 of 10
      patients studied. Despite the ongoing presence of hPIV-3 outside the
      inpatient/outpatient care continuum clinic, only 2 cases were observed after
      institution of respiratory season infection control measures. CONCLUSIONS: This
      investigation demonstrates the utility of surveillance software in the
      identification of respiratory virus outbreaks and the importance of rapid
      implementation of infection control/prevention measures for containment of
      outbreaks.

PMID- 22405749
TI  - Hidden beauty.

PMID- 22405750
TI  - Comparison of different procedures to stabilize biogas formation after process
      failure in a thermophilic waste digestion system: influence of aggregate
      formation on process stability.
AB  - Following a process failure in a full-scale biogas reactor, different counter
      measures were undertaken to stabilize the process of biogas formation, including
      the reduction of the organic loading rate, the addition of sodium hydroxide
      (NaOH), and the introduction of calcium oxide (CaO). Corresponding to the results
      of the process recovery in the full-scale digester, laboratory experiments showed
      that CaO was more capable of stabilizing the process than NaOH. While both
      additives were able to raise the pH to a neutral milieu (pH>7.0), the formation
      of aggregates was observed particularly when CaO was used as the additive.
      Scanning electron microscopy investigations revealed calcium phosphate compounds
      in the core of the aggregates. Phosphate seemed to be released by phosphorus
      accumulating organisms, when volatile fatty acids accumulated. The calcium, which
      was charged by the CaO addition, formed insoluble salts with long chain fatty
      acids, and caused the precipitation of calcium phosphate compounds. These
      aggregates were surrounded by a white layer of carbon rich organic matter,
      probably consisting of volatile fatty acids. Thus, during the process recovery
      with CaO, the decrease in the amount of accumulated acids in the liquid phase was
      likely enabled by (1) the formation of insoluble calcium salts with long chain
      fatty acids, (2) the adsorption of volatile fatty acids by the precipitates, (3)
      the acid uptake by phosphorus-accumulating organisms and (4) the degradation of
      volatile fatty acids in the aggregates. Furthermore, this mechanism enabled a
      stable process performance after re-activation of biogas production. In contrast,
      during the counter measure with NaOH aggregate formation was only minor resulting
      in a rapid process failure subsequent the increase of the organic loading rate.

PMID- 22405751
TI  - Centralized PI controllers for interacting multivariable processes by synthesis
      method.
AB  - In this article, two methods of designing a centralized control system for multi
      input, multi-output (MIMO) processes are presented. Centralized proportional
      integral (PI) controllers are designed based on a direct synthesis method. The
      inverse of the process transfer function matrix in the direct synthesis method is
      approximated based on the relative gain array concept. The method is further
      improved by using a relative normalized gain array, and an equivalent transfer
      function for each element in the process transfer function matrix is derived for
      the closed-loop control system. The transpose of the effective transfer function
      is used to approximate the inverse of the process transfer function matrix. The
      simulation studies demonstrate the effectiveness of this method. The proposed
      centralized controllers reduce the interactions better than recently reported
      decentralized controllers do. A centralized controller designed based on a
      relative normalized gain array (RNGA) gives a better performance than a
      centralized controller designed based on a relative gain array (RGA).

PMID- 22405752
TI  - Sliding mode fault tolerant control dealing with modeling uncertainties and
      actuator faults.
AB  - In this paper, two sliding mode control algorithms are developed for nonlinear
      systems with both modeling uncertainties and actuator faults. The first algorithm
      is developed under an assumption that the uncertainty bounds are known. Different
      design parameters are utilized to deal with modeling uncertainties and actuator
      faults, respectively. The second algorithm is an adaptive version of the first
      one, which is developed to accommodate uncertainties and faults without utilizing
      exact bounds information. The stability of the overall control systems is proved
      by using a Lyapunov function. The effectiveness of the developed algorithms have
      been verified on a nonlinear longitudinal model of Boeing 747-100/200.

PMID- 22405753
TI  - Mining for liquid gold: midwifery language and practices associated with early
      breastfeeding support.
AB  - Internationally, women give mixed reports regarding professional support during
      the early establishment of breastfeeding. Little is known about the components of
      midwifery language and the support practices, which assist or interfere with the
      early establishment of breastfeeding. In this study, critical discourse analysis
      has been used to describe the language and practices used by midwives when
      supporting breastfeeding women during the first week after birth. Participant
      observation at two geographically distant Australian health care settings
      facilitated the collection of 85 observed audio-recorded dyadic interactions
      between breastfeeding women and midwives during 2008-2009. Additionally, 23
      interviews with women post discharge, 11 interviews with midwives and four focus
      groups (40 midwives) have also been analysed. Analysis revealed three discourses
      shaping the beliefs and practices of participating midwives. In the dominant
      discourse, labelled 'Mining for Liquid Gold', midwives held great reverence for
      breast milk as 'liquid gold' and prioritised breastfeeding as the mechanism for
      transfer of this superior nutrition. In the second discourse, labelled 'Not
      Rocket Science', midwives constructed breastfeeding as 'natural' or 'easy' and
      something which all women could do if sufficiently committed. The least well
      represented discourse constructed breastfeeding as a relationship between mother
      and infant. In this minority discourse, women were considered to be knowledgeable
      about their needs and those of their infant. The language and practices of
      midwives in this approach facilitated communication and built confidence. These
      study findings suggest the need for models of midwifery care, which facilitate
      relationship building between mother and infant and mother and midwife.

PMID- 22405754
TI  - Microbial degradation of n-hexadecane in mineral salt medium as mediated by
      degradative enzymes.
AB  - In the present study, n-hexadecane degradation in MSM was investigated by three
      bacteria identified as Pseudomonas aeruginosa PSA5, Rhodococcus sp. NJ2 and
      Ochrobactrum intermedium P2, isolated from petroleum sludge. During 10 days of
      incubation, n-hexadecane was degraded to 99% by P. aeruginosa PSA5, 95% by
      Rhodococcus sp. NJ2 and 92% by O. intermedium P2. During degradation process, the
      induction of catabolic enzymes alkane hydroxylase, alcohol dehydrogenase and
      lipase were also examined. Among these enzymes, the highest activities of alkane
      hydroxylase (185 MUmol mg(-1) protein) and alcohol dehydrogenase (75.78 MUmol mg(
      1) protein) were recorded in Rhodococcus sp. NJ2 while lipase activity was highly
      induced in P. aeruginosa PSA5 (48.71 MUmol mg(-1) protein). Besides, accumulation
      of n-hexadecane in inclusion bodies was found to be maximum 60.8 g l(-1) in P.
      aeruginosa PSA5, followed by Rhodococcus sp. NJ2 (56.1 g l(-1)) and the least
      (51.6 g l(-1)) was found in O. intermedium P2. Biosurfactant production by
      bacterial strains was indicated by the reduction in surface tension and induction
      of cell surface hydrophobicity and pseudosolubilization which facilitated n
      hexadecane degradation.

PMID- 22405755
TI  - A critical review of emission standards and regulations regarding biomass
      combustion in small scale units (<3 MW).
AB  - Wood and agricultural crop residues are abundant, renewable and relatively low
      cost biomasses. Their combustion can replace fossil fuels in several
      applications. A major concern with biomass combustion is the emission of
      particulate matter (PM) in the atmosphere. The World Health Organization (WHO)
      has developed ambient air quality guidelines, notably maximum average annual
      levels of 20 MUg/m(3) for PM10 (particulate matter<10 MUm). Combustion standards
      generally assess total PM at the chimney stack, with variable levels depending on
      local legislation, industrial activity, population density, etc. (e.g. 100
      200mg/m(3) in Massachusetts, 150 mg/m(3) in Quebec, and 600 mg/m(3) in New York).
      Some areas mandate relatively low PM levels from boilers (50mg/m(3) in Europe,
      20mg/m(3) in Germany starting in 2015). The availability of conditioned and
      relatively dry biomass, along with PM removal technologies (e.g. cyclones,
      scrubbers, precipitators, and baghouse filters), will become important
      requirements for future biomass combustion.

PMID- 22405756
TI  - Utilization of crude karanj (Pongamia pinnata) oil as a potential feedstock for
      the synthesis of fatty acid methyl esters.
AB  - Methyl esters were synthesized from crude karanj oil (CKO) by single step
      esterification with methanol using sulfuric acid (H(2)SO(4)) and phosphoric acid
      (H(3)PO(4)) as catalysts in a homogeneous batch process. H(3)PO(4) was less
      active than H(2)SO(4) during the process as it presented very low ester yields
      (<20%) for the various molar ratios of fatty acid to alcohol studied. With
      H(2)SO(4) as catalyst, the yield was as high as 89.8% at 65 degrees C after 5h.
      The fatty acids profile of the oil (palmitic acid: ~ 12%; stearic acid: ~ 8%;
      oleic acid: ~ 52% and linolenic acid of 17%) and the different reactivities of
      the acids were responsible for the observed differences in conversion to methyl
      esters. The findings attained with this study might contribute to the economic
      utilization of a non-edible feedstock.

PMID- 22405757
TI  - Maximizing biodiesel production from Yarrowia lipolytica Po1g biomass using
      subcritical water pretreatment.
AB  - The yeast Yarrowia lipolytica Po1g is one of the oleaginous microorganisms with a
      potential for biodiesel production. Sub-critical water (SCW) treatment has been
      known as an effective method for increasing the amount of extractable lipids in
      microorganisms. In this work, the amount of neutral lipids and fatty acid
      profiles in neutral lipids extracted from Y. lipolytica Po1g with and without SCW
      pre-treatment were investigated. The effects of temperature (125, 150 or 175
      degrees C), amount of water (20, 30 or 40 mL/g biomass) and time (10, 20 or 30
      min) showed that maximum neutral lipid (42.69%, w/w) could be achieved at 175
      degrees C using 20 mL water for 20 min. The maximum neutral lipid from
      unpretreated samples was 23.21%. No difference in fatty acid profiles was
      observed, but long chain fatty acids were observed in higher amount in SCW
      pretreated samples. SCW pretreatment increased biodiesel yield twofold.

PMID- 22405758
TI  - Life cycle assessment of the integrated generation of solid fuel and biogas from
      biomass (IFBB) in comparison to different energy recovery, animal-based and non
      refining management systems.
AB  - The study compares energy production from semi-natural grasslands by the
      integrated generation of solid fuel and biogas from biomass (IFBB) through
      mechanical separation of the biomass with the dry fermentation (DF) and hay
      combustion system (HC). In addition, traditional use for beef cattle production
      and non-refining systems of landscape conservation, i.e. mulching and composting,
      are considered. Highest conversion efficiency (45-54% of the gross yield), net
      savings of fossil fuels (44-54 GJ ha(-1)) and net savings of greenhouse gases
      (2.9-3.7 t CO(2-eq)ha(-1)) are obtained by HC and IFBB. Potentials of DF are
      limited due to low digestibility of the mature biomass.

PMID- 22405759
TI  - Impact of influent characteristics on a partial nitritation SBR treating high
      nitrogen loaded wastewater.
AB  - The Anammox process allows a sustainable treatment of wastewater with high
      nitrogen content. Partial oxidation of ammonium to nitrite is a previous and
      crucial step. Given the variability on wastewater composition, the operation of
      sequencing batch reactors (SBR) for partial nitritation (PN) is very challenging.
      This work assessed the combined influence of influent characteristics and process
      loading rate. Simulation results showed that wastewater composition - Total
      nitrogen as ammonia (TNH) and total inorganic carbon (TIC) - as well as nitrogen
      loading rate (NLR) govern the outcomes of the reactor. A suitable effluent can be
      produced when treating wastewater with different ammonia levels, as long as the
      TIC:TNH influent molar ratio is around 1:1 and extreme NLR are avoided. The
      influent pH has a key impact on nitrite conversion by governing the CO(2)
      bicarbonate-carbonate equilibrium. Finally, results showed that oxidation of
      biodegradable organic matter produces CO(2), which acidifies the media and limits
      process conversion.

PMID- 22405761
TI  - Structural characterisation of a histone domain by projection-decomposition.
AB  - We demonstrate that two projection experiments, a (15)N-HSQC-NOESY-(15)N-HSQC and
      a (13)C-HSQC-NOESY-(15)N-HSQC, recorded for a histone domain from yeast, contain
      enough information to support a structural characterisation of the protein. At
      the temperature used, 298 K, the histone domain exhibits a very high extent of
      chemical shift degeneracy that is uncharacteristic for a fully folded domain.
      Nonetheless, a structured core of 67 residues, which is formed by three alpha
      helices and a two-stranded beta-sheet is defined by this NOESY data; this core
      structure was shown earlier to be present at lower temperature. The above two
      experiments, which together required 18 h of instrument time, are part of a set
      of five projection experiments acquired during 2.5 days with the goal of complete
      characterisation of proteins, including full resonance assignment and structure.

PMID- 22405760
TI  - A method for simultaneous echo planar imaging of hyperpolarized 13C pyruvate and
      13C lactate.
AB  - A rapid echo planar imaging sequence for dynamic imaging of [1-(13)C] lactate and
      [1-(13)C] pyruvate simultaneously was developed. Frequency-based separation of
      these metabolites was achieved by spatial shifting in the phase-encoded direction
      with the appropriate choice of echo spacing. Suppression of the pyruvate-hydrate
      and alanine resonances is achieved through an optimized spectral-spatial RF
      waveform. Signal sampling efficiency as a function of pyruvate and lactate
      excitation angle was simulated using two site exchange models. Dynamic imaging is
      demonstrated in a transgenic mouse model, and phantom validations of the RF pulse
      frequency selectivity were performed.

PMID- 22405762
TI  - Silver nanoparticles: a potential nanocatalyst for the rapid degradation of
      starch hydrolysis by alpha-amylase.
AB  - Silver nanoparticles (AgNPs) are proven to be an effective catalytic material for
      various applications due to their excellent optical and electronic properties. In
      this paper, we describe a novel approach for the degradation of starch using the
      catalytic behaviour of AgNPs in an enzyme catalysed reaction of starch hydrolysis
      by alpha-amylase. AgNPs were synthesized by soluble starch reducing silver
      nitrate to silver atoms. An increase of 4.7-fold in reducing sugar formation and
      1.5 times faster enzyme activity confirmed the catalytic activity of AgNPs as a
      nanocatalyst. Surprisingly, starch degradation tests revealed that 9.9 mg of
      starch was hydrolysed within 5 min, which corroborates with the reducing sugar
      assay. In short, the present study paves way for the faster degradation of starch
      by immobilizing the enzyme onto the surface of the AgNP, which could be a
      promising application in the food industry.

PMID- 22405763
TI  - Growth hormone (GH) and brain trauma.
AB  - Growth hormone (GH) is a pleiotropic hormone with known neurotrophic effects. We
      aimed to study whether GH administration might be useful together with
      rehabilitation in the recovery of TBI patients. 13 TBI patients (8 M, 5 F; age: 6
      53 years old) were studied. Time after TBI: 2.5 months to 11 years; 5 patients
      showed acquired GH-deficiency (GHD). Disabilities observed: cognitive disorders;
      motor plegias; neurogenic dysphagia (n=5), vegetative coma (n=2) and amaurosis
      (n=1). All but one TBI patient followed intense rehabilitation for years.
      Treatment consisted of GH administration (maximal dose 1 mg/day, 5 days/week,
      resting 15-days every 2-months, until a maximum of 8 months) and clinical
      rehabilitation according to the individual needs (3-4 h/day, 5 days/week, during
      6-12 months). Informed consent was obtained before commencing GH administration.
      GH significantly increased plasma IGF-1 values (ng.mL(-1)) in both GHD and no GHD
      patients, being then similar between both groups (GHD: 275.6+/-35.6 [p<0.01 vs.
      baseline], no GHD: 270.2+/-64 [p<0.05 vs. baseline]). In all the cases clear
      significant improvements were observed during and at the end of the combined
      treatment. Cognitive improvements appeared earlier and were more important than
      motor improvements. Swallowing improved significantly in all TBI patients with
      neurogenic dysphagia (2 of them in a vegetative state). Visual performance was
      ameliorated in the patient with amaurosis. No undesirable side-effects were
      observed. Our data indicate that GH can be combined with rehabilitation for
      improving disabilities in TBI patients, regardless of whether or not they are
      GHD.

PMID- 22405764
TI  - DACH1 regulates cell cycle progression of myeloid cells through the control of
      cyclin D, Cdk 4/6 and p21Cip1.
AB  - The cell-fate determination factor Dachshund, a component of the Retinal
      Determination Gene Network (RDGN), has a role in breast tumor proliferation
      through the repression of cyclin D1 and several key regulators of embryonic stem
      cell function, such as Nanog and Sox2. However, little is known about the role of
      DACH1 in a myeloid lineage as a cell cycle regulator. Here, we identified the
      differential expression levels of extensive cell cycle regulators controlled by
      DACH1 in myeloid progenitor cells. The forced expression of DACH1 induced
      p27(Kip1) and repressed p21(Cip1), which is a pivotal characteristic of the
      myeloid progenitor. Furthermore, DACH1 significantly increased the expression of
      cyclin D1, D3, F, and Cdk 1, 4, and 6 in myeloid progenitor cells. The knockdown
      of DACH1 blocked the cell cycle progression of HL-60 promyeloblastic cells
      through the decrease of cyclin D1, D3, F, and Cdk 1, 4, and 6 and increase in
      p21(Cip1), which in turn decreased the phosphorylation of the Rb protein. The
      expression of Sox2, Oct4, and Klf4 was significantly up-regulated by the forced
      expression of DACH1 in mouse myeloid progenitor cells.

PMID- 22405765
TI  - ROCK inhibitor prevents the dedifferentiation of human articular chondrocytes.
AB  - Chondrocytes lose their chondrocytic phenotypes in vitro. The Rho family GTPase
      ROCK, involved in organizing the actin cytoskeleton, modulates the
      differentiation status of chondrocytic cells. However, the optimum method to
      prepare a large number of un-dedifferentiated chondrocytes is still unclear. In
      this study, we investigated the effect of ROCK inhibitor (ROCKi) on the
      chondrogenic property of monolayer-cultured articular chondrocytes. Human
      articular chondrocytes were subcultured in the presence or absence of ROCKi (Y
      27632). The expression of chondrocytic marker genes such as SOX9 and COL2A1 was
      assessed by quantitative real-time PCR analysis. Cellular morphology and
      viability were evaluated. Chondrogenic redifferentiation potential was examined
      by a pellet culture procedure. The expression level of SOX9 and COL2A1 was higher
      in ROCKi-treated chondrocytes than in untreated cells. Chondrocyte morphology
      varied from a spreading form to a round shape in a ROCKi-dependent manner. In
      addition, ROCKi treatment stimulated the proliferation of chondrocytes. The
      deposition of safranin O-stained proteoglycans and type II collagen was highly
      detected in chondrogenic pellets derived from ROCKi-pretreated chondrocytes. Our
      results suggest that ROCKi prevents the dedifferentiation of monolayer-cultured
      chondrocytes, and may be a useful reagent to maintain chondrocytic phenotypes in
      vitro for chondrocyte-based regeneration therapy.

PMID- 22405766
TI  - 4-Hydroxy-2-nonenal induces chronic obstructive pulmonary disease-like
      histopathologic changes in mice.
AB  - The alpha,beta-unsaturated aldehyde 4-hydroxy-2-nonenal (4-HNE) is an endogenous
      product of oxidative stress that is found at increased levels in the lungs of
      patients with chronic obstructive pulmonary disease (COPD) and animal models of
      this lung disorder. In the present study, levels of 4-HNE adducts were increased
      in two different mouse models of COPD. Challenging lungs with 4-HNE enlarged the
      airspace and induced goblet cell metaplasia of the airways in mice, two
      characteristics of COPD. 4-HNE induced the accumulation of inflammatory cells
      expressing high levels of MMP-2 and MMP-9. Our results indicate that 4-HNE
      production during oxidative stress is a key pathway in the pathogenesis of COPD.

PMID- 22405767
TI  - Methionine sulfoxide reductase B3 protects from endoplasmic reticulum stress in
      Drosophila and in mammalian cells.
AB  - Methionine sulfoxide reductase B3A (MsrB3A), which catalyzes the stereospecific
      reduction of methionine-R-sulfoxide to methionine, is localized to the
      endoplasmic reticulum (ER). Here, we report a critical role of the ER-targeted
      MsrB3 in protection against ER stress in Drosophila and in mammalian cells. Flies
      overexpressing human MsrB3A exhibited significantly increased resistance to ER
      stress induced by dithiothreitol. These flies also showed slightly enhanced
      resistance to tunicamycin-induced ER stress. In addition, overexpression of
      MsrB3A in mammalian cells increased resistance to dithiothreitol- and
      thapsigargin-induced ER stresses. However, MsrB3A overexpression had no effect on
      the resistance to tunicamycin-induced ER stress. Knockdown of MsrB3A in mammalian
      cells led to a significant decrease in the resistance to thapsigargin-induced ER
      stress, but had no effects on the resistance to either dithiothreitol- or
      tunicamycin-induced ER stress. Collectively, our data provide evidence that the
      ER-type of MsrB3 plays an important role in protection against ER stress,
      suggesting that MsrB3 may be involved in the regulation of ER homeostasis.

PMID- 22405768
TI  - Peptide-surfactant interactions: consequences for the amyloid-beta structure.
AB  - The conformation of amyloid-beta peptide (Abeta) determines if toxic aggregates
      are formed. The peptide structure by its turn depends on the environment and
      molecule-molecule interactions. We characterized the secondary structure of Abeta
      (1-40) in surfactant solutions and interacting with monolayers. The peptide
      adopts beta-sheet structure in solutions of ionic surfactants at sub-micelle
      concentrations and alpha-helix in the presence of ionic micelles. Uncharged
      micelles induce beta-sheets. Abeta-(1-40) alters the critical micelle
      concentration value of the non-ionic surfactant, underlining hydrophobic
      interactions. At ionic monolayers the peptide forms beta-sheets when its
      concentration at the surface is high enough. These results suggest that only
      electrostatic interactions of charged micelles that surround completely the
      peptide are able to induce non-aggregated alpha-helix structure.

PMID- 22405769
TI  - Th2-inducing cytokines IL-4 and IL-33 synergistically elicit the expression of
      transmembrane TNF-alpha on macrophages through the autocrine action of IL-6.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a potent proinflammatory cytokine
      produced predominantly by activated macrophages, and plays a central role in the
      protective immunity against intracellular pathogens and the pathogenesis of
      autoimmune and inflammatory diseases. While both the soluble and transmembrane
      forms of TNF-alpha (sTNF-alpha and tmTNF-alpha) are biologically functional, the
      latter but not the former acts as a receptor besides as a ligand, and transmit a
      retrograde signal in a cell-to-cell contact manner. The production of TNF-alpha
      by macrophages under Th2-type (allergic) inflammatory conditions has been ill
      defined, compared to that under Th1-type inflammatory conditions. Here we
      examined the effect of representative Th2-inducing cytokines IL-4 and IL-33 on
      the TNF-alpha expression in macrophages. IL-4 induced the production of neither
      sTNF-alpha nor tmTNF-alpha while IL-33 promoted the production of sTNF-alpha with
      no detectable tmTNF-alpha. Notably, the combination of IL-4 and IL-33 elicited
      the tmTNF-alpha expression on macrophages, in addition to the enhanced production
      of sTNF-alpha and IL-6. The IL-4/IL-33-elicited tmTNF-alpha expression was not
      observed in IL-6-deficient macrophages, suggesting the involvement of macrophage
      derived IL-6 in the tmTNF-alpha expression. Indeed, the stimulation of
      macrophages with the combination of IL-4 and IL-6 induced the tmTNF-alpha
      expression with no detectable production of sTNF-alpha. Thus, IL-4 and IL-33
      synergistically elicit the tmTNF-alpha expression on macrophages through the
      autocrine action of IL-6.

PMID- 22405770
TI  - Temperature dependent N-glycosylation of plasma membrane heat shock protein
      Hsp30p in Saccharomyces cerevisiae.
AB  - The HSP30 gene of the budding yeast Saccharomyces cerevisiae encodes a seven
      transmembrane heat shock protein expressed in response to various types of stress
      including heat shock. Although Hsp30p contains a potential N-glycosylation
      consensus sequence (Asn(2)-Asp(3)-Thr(4)), whether it is actually N-glycosylated
      has not been verified. Here we demonstrate that N-glycosylation is induced at
      Asn(2) of Hsp30p by severe heat shock, ethanol stress, and acetic acid stress.
      Mild heat shock and glucose depletion induced the expression but not N
      glycosylation of Hsp30p, indicating the N-glycosylation to be dependent on
      temperature and environmental conditions. N-glycosylation did not affect on the
      intracellular localization of Hsp30p but its physiological role under severe heat
      shock conditions. Since limited information is available on stress-responsive or
      condition-induced N-glycosylation, our findings provide new insight into the
      regulation of cellular stress response in yeast.

PMID- 22405771
TI  - The receptor for advanced glycation endproducts and its ligands in patients with
      myasthenia gravis.
AB  - OBJECTIVE: Myasthenia gravis (MG) is a T- and B-cell mediated autoimmune disorder
      affecting the neuromuscular junction. The receptor for advanced glycation
      endproducts (RAGE) plays a role in the amplification of chronic inflammatory
      disorders and autoimmune diseases. We sought to investigate the role of RAGE and
      its ligands in the pathophysiology of MG. METHODS: In this cross-sectional study
      we enrolled 42 patients with MG and 36 volunteers. We employed enzyme-linked
      immunosorbent assays to determine the concentration of soluble RAGE (sRAGE) and
      high mobility group box 1 (HMGB1) in serum of patients and volunteers. In a
      subpopulation of patients we measured the serum levels of endogenous secretory
      (es) RAGE and various RAGE ligands, such as S100B, S100A8 and advanced glycation
      endproducts (AGE-CML). Reported are means and standard error mean. RESULTS: We
      found significantly reduced levels of the soluble receptors sRAGE and esRAGE in
      patients with MG compared to volunteers without MG (sRAGE [pg/ml] 927.2 +/- 80.8
      vs. 1400.1 +/- 92.4; p<0.001; esRAGE [pg/ml] 273.5+/-24.6 vs. 449.0 +/- 22.4;
      p<0.001). Further categorization of patients with MG according to the
      distribution of muscle involvement revealed the following sRAGE concentrations:
      generalized MG 999.4 +/- 90.8 and ocular MG 696.1 +/- 161.8 (vs. control; One-way
      ANOVA: p<0.001; Post hoc analysis: generalized vs. ocular MG: p=0.264,
      generalized MG vs. control: p=0.008, ocular MG vs. control: p=0.001). In patients
      with detectable antibodies specific for acetylcholine receptors (Anti-AChR
      positive) the sRAGE concentration was 970.0 +/- 90.2 compared to those without
      (seronegative) 670.6 +/- 133.1 (vs. control; One-way ANOVA: p<0.001; Post hoc
      analysis: Pos vs. Neg.: p=0.418, Pos vs. control: p=0.003, Neg. vs. control:
      p=0.008). We next investigated the role of RAGE ligands in MG. The concentrations
      of RAGE ligands in patients with MG and controls were as follows: (HMGB1 [ng/ml]
      1.7 +/- 0.1 vs. 2.1 +/- 0.2; p=0.058; S100B [pg/ml] 22.5 +/- 22.5 vs. 14.4 +/-
      9.2; p=0.698; S100A8 [pg/ml] 107.0 +/- 59.3 vs. 242.5 +/- 103.6; p=0.347; and AGE
      CML [ng/ml] 1100.8 +/- 175.1 vs. 1399.8 +/- 132.8; p=0.179). CONCLUSIONS: Our
      data suggest a role for the RAGE pathway in the pathophysiology of MG. Further
      studies are warranted to elucidate more about this immunological axis in patients
      with MG.

PMID- 22405772
TI  - Regulation of P2X7-dependent inflammatory functions by P2X4 receptor in mouse
      macrophages.
AB  - Activation of the P2X7 receptor of macrophages plays an important role in
      inflammation. We recently reported that co-expression of P2X4 receptor with P2X7
      receptor facilitates P2X7 receptor-mediated cell death via Ca(2+) influx.
      However, it remained unclear whether P2X4 receptor is involved in P2X7 receptor
      mediated inflammatory responses, such as cytokine production. Here, we present
      evidence that P2X4 receptor modulates P2X7 receptor-dependent inflammatory
      functions. Treatment of mouse macrophage RAW264.7 cells with 1mM ATP induced high
      mobility group box 1 (HMGB1) release and IL-1beta production via activation of
      P2X7 receptor. Knockdown of P2X4 receptor or removal of extracellular Ca(2+)
      suppressed ATP-induced release of both HMGB1 and IL-1beta. On the other hand,
      knockdown of P2X4 receptor or removal of extracellular Ca(2+) enhanced P2X7
      dependent LC3-II expression (an index of autophagy), suggesting that P2X4
      receptor suppresses P2X7-mediated autophagy. Since LC3-II expression was
      inhibited by pretreatment with antioxidant and NADPH oxidase inhibitor, we
      examined P2X7-mediated production of reactive oxygen species (ROS). We found that
      activation of P2X7 receptor-mediated production of ROS was significantly
      facilitated in P2X4-knockdown cells, suggesting that co-expression of P2X4
      receptor with P2X7 receptor may suppress anti-inflammatory function-related
      autophagy via suppression of ROS production. We conclude that co-expression of
      P2X4 receptor with P2X7 receptor enhances P2X7-mediated inflammation through both
      facilitation of release of cytokines and suppression of autophagy.

PMID- 22405773
TI  - Chondroregulatory action of prolactin on proliferation and differentiation of
      mouse chondrogenic ATDC5 cells in 3-dimensional micromass cultures.
AB  - A recent investigation in lactating rats has provided evidence that the
      lactogenic hormone prolactin (PRL) increases endochondral bone growth and bone
      elongation, presumably by accelerating apoptosis of hypertrophic chondrocytes in
      the growth plate and/or subsequent chondrogenic matrix mineralization. Herein, we
      demonstrated the direct chondroregulatory action of PRL on proliferation,
      differentiation and apoptosis of chondrocytes in 3-dimensional micromass culture
      of mouse chondrogenic ATDC5 cell line. The results showed that ATDC5 cells
      expressed PRL receptor (PRLR) transcripts, and responded typically to PRL by
      downregulating PRLR expression. Exposure to a low PRL concentration of 10 ng/mL,
      comparable to the normal levels in male and non-pregnant female rats, increased
      chondrocyte viability, differentiation, proteoglycan accumulation, and mRNA
      expression of several chondrogenic differentiation markers, such as Sox9, ALP and
      Hspg2. In contrast, high PRL concentrations of >= 100 ng/mL, comparable to the
      levels in pregnancy or lactation, decreased chondrocyte viability by inducing
      apoptosis, with no effect on chondrogenic marker expression. It could be
      concluded that chondrocytes directly but differentially responded to non-pregnant
      and pregnant/lactating levels of PRL, thus suggesting the stimulatory effect of
      PRL on chondrogenesis in young growing individuals, and supporting the hypothesis
      of hypertrophic chondrocyte apoptosis in the growth plate of lactating rats.

PMID- 22405774
TI  - Phospholamban mutants compete with wild type for SERCA binding in living cells.
AB  - We have used fluorescent fusion proteins stably expressed in HEK cells to detect
      directly the interaction between the sarcoplasmic reticulum Ca-ATPase (SERCA) and
      phospholamban (PLB) in living cells, in order to design PLB mutants for gene
      therapy. Ca(2+) cycling in muscle cells depends strongly on SERCA. Heart failure
      (HF), which contributes to 12% of US deaths, typically exhibits decreased SERCA
      activity, and several potential therapies for HF aim to increase SERCA activity.
      We are investigating the use of LOF-PLB mutants (PLB(M)) as gene therapy vectors
      to increase SERCA activity. Active SERCA1a and WT-PLB, tagged at their N termini
      with fluorescent proteins (CFP and YFP), were coexpressed in stable HEK cell
      lines, and fluorescence resonance energy transfer (FRET) was used to detect their
      interaction directly. Phosphorylation of PLB, induced by forskolin, caused an
      increase in FRET from CFP-SERCA to YFP-PLB, indicating that SERCA inhibition can
      be relieved without dissociation of the complex. This suggests that a LOF mutant
      might bind to SERCA with sufficient affinity to complete effectively with WT-PLB,
      thus relieving SERCA inhibition. Therefore, we transiently expressed a series of
      PLB(M) in the CFP-SERCA/YFP-PLB cell line, and found decreased FRET, implying
      competition between PLB(M) and WT-PLB for binding to SERCA. These results
      establish this FRET assay as a rapid and quantitative means of screening PLB(M)
      for optimization of gene therapy to activate SERCA, as needed for gene therapy in
      HF.

PMID- 22405775
TI  - Sex differences in cannabinoid receptor-1 (CB1) pharmacology in mice selectively
      bred for high voluntary wheel-running behavior.
AB  - The endocannabinoid system (ECS) is involved in regulation of various
      physiological functions, including locomotion, antinociception, emotional states,
      and motivated behaviors. The ECS has been implicated in regulation of voluntary
      wheel running in mice via actions at the cannabinoid receptor-1 (CB1).
      Previously, we showed that four replicate lines of mice bred for high levels of
      voluntary wheel running (high-runner or HR lines) sex-specifically (females only)
      decreased running in response to antagonism of the CB1 receptor, as compared with
      four unselected Control lines. Here, we administered a CB1 receptor agonist, WIN
      55,212-2 (WIN). We predicted that if CB1 activation is involved in the regulation
      of voluntary wheel running, then HR mice would show a greater response to CB1
      agonism. Following our previous protocols, mice from generation 53 were
      acclimated to running wheels for 24 days, then received, in random order, either
      an intra-peritoneal injection of vehicle or a low (0.5 mg/kg), medium (1 mg/kg)
      or high dosage (3 mg/kg) of WIN. Each mouse received an injection and then
      experienced two nights without injections, for a total period of 12 days.
      Response to WIN was quantified as wheel revolutions, time spent running, and
      average running speed in the 10-120 min immediately following injection.
      Injection decreased wheel revolutions in all mice, but male HR mice decreased
      their running to a greater degree relative to Controls in response to the high
      dose of WIN over the entire period analyzed, whereas HR females showed a
      differential response relative to Controls only in the latter 70-120 min post
      injection. These results, in conjunction with our previous study, show that (a)
      aspects of endocannabinoid signaling have diverged in four lines of mice bred for
      high levels of voluntary exercise and (b) male and female HR mice differ from one
      another in CB1 signaling as it relates to wheel running.

PMID- 22405776
TI  - Selective and nonselective neuronal NOS inhibitors impair cognitive function in
      the three panel runway and passive avoidance tasks in rats.
AB  - The aim of this study was to compare the effects of both neuronal NOS (nNOS) and
      inducible NOS (iNOS) inhibitor 2-iminobiotin, with the more selective nNOS
      inhibitor N(omega)-propyl-L-arginine (NPLA) and selective inducible NOS (iNOS)
      inhibitor aminoguanidine, on emotional learning, working memory and reference
      memory, by using three panel runway and passive avoidance paradigm in order to
      clarify the role of distinct isoforms of NOS in the regulation of learning and
      memory functions. NPLA and 2-iminobiotin significantly increased the number of
      errors and latency of working and reference memory performances of rats in three
      panel runway paradigm and impairs retention for the passive avoidance task.
      However, aminoguanidine did not affect cognitive functions in three panel runway
      and passive avoidance test. The effect of NPLA and 2-iminobiotin was reversed by
      pretreatment with a NOS substrate L-arginine. In conclusion, NPLA and 2
      iminobiotin impaired cognitive functions in different kind of tasks used in this
      study and the effect of NPLA and 2-iminobiotin was found to be NO-dependent. Our
      results may confirm that nNOS plays the key role on emotional learning, working
      memory and reference memory in rats.

PMID- 22405777
TI  - Chronic psychostimulant exposure to adult, but not periadolescent rats reduces
      subsequent morphine antinociception.
AB  - Preweanling methylphenidate (MPH) exposure produces a long lasting enhanced
      sensitivity to opioids. Two important questions are whether this enhancement is
      specific to the age of psychostimulant exposure and the type of psychostimulant.
      To answer these questions periadolescent (PD 35) and adult (PD 55) rats received
      daily injections of saline, MPH, or methamphetamine (METH) for 10 consecutive
      days. Two weeks later, acute morphine antinociception was assessed on the hot
      plate using a cumulative dose response procedure. Following acute antinociceptive
      testing, morphine tolerance was induced in half the animals by administering
      morphine twice a day over 2 days. Rats pretreated with MPH and METH during the
      periadolescent period of ontogeny showed no change in acute morphine
      antinociception, but rats exposed to a relatively high METH dose (3 mg/kg)
      displayed enhanced morphine tolerance compared to saline pretreated controls. MPH
      and METH pretreatment during adulthood led to a reduction in morphine
      antinociceptive potency and an apparent reduction in morphine tolerance. When
      combined with our previously published findings, these data indicate that the
      developmental stage during which MPH and METH exposure occurs differentially
      alters adult morphine responsiveness. That is, psychostimulant exposure to
      preweanling rats enhances morphine antinociception and facilitates the
      development of tolerance, whereas psychostimulant exposure to adult rats reduces
      subsequent morphine antinociception and tolerance. These alterations indicate
      that it could be important for physicians to know about prior psychostimulant use
      when prescribing opioids for pain relief.

PMID- 22405778
TI  - Effects of apomorphine on mating behavior, flank marking and aggression in male
      hamsters.
AB  - In male rats, the dopamine agonist apomorphine (APO) generally facilitates
      copulatory behavior. However, disruptive effects of high APO doses have been
      reported. These have been interpreted in diverse ways, as products of a
      dopaminergic system that inhibits sexual behavior or as consequences of APO's
      stimulation of competing responses. To test the generality of these effects, we
      observed APO's impact on copulatory behavior in male hamsters. Several effects
      were observed, all attributable to a relatively high dose and involving the
      disruption of male behavior. More unexpectedly, APO treatment caused males to
      attack estrous stimulus females in the course of these tests. To clarify these
      effects, we observed the effects of APO on flank marking, a type of scent marking
      closely allied to aggression and dominance in hamsters. Treatment reliably
      decreased the latency of marking. It also increased the rate of marking when
      appropriate measures were taken to prevent this effect from being obscured by
      drug-induced cheek pouching. Together, these results confirm and extend APO's
      well-known ability to increase aggression. Further, they suggest that APO-induced
      aggression can intrude into other contexts so as to disrupt, or possibly
      facilitate, other forms of social behavior.

PMID- 22405779
TI  - Folding studies on muscle type of creatine kinase from Pelodiscus sinensis.
AB  - A folding study of creatine kinase from Pelodiscus sinensis has not yet been
      reported. To gain more insight into structural and folding mechanisms of P.
      sinensis CK (PSCK), denaturants such as SDS, guanidine HCl, and urea were applied
      in this study. We purified PSCK from the muscle of P. sinensis and conducted
      inhibition kinetics with structural unfolding studies under various conditions.
      The results revealed that PSCK was completely inactivated at 1.8 mM SDS, 1.05 M
      guanidine HCl, and 7.5 M urea. The kinetics via time-interval measurements showed
      that the inactivation by SDS, guanidine HCl, and urea were all first-order
      reactions with kinetic processes shifting from monophase to biphase at increasing
      concentrations. With respect to tertiary structural changes, PSCK was unfolded in
      different ways; SDS increased the hydrophobicity but retained the most tertiary
      structural conformation, while guanidine HCl and urea induced conspicuous changes
      in tertiary structures and initiated kinetic unfolding mechanisms. Our study
      provides information regarding PSCK and enhances our knowledge of the reptile
      derived enzyme folding.

PMID- 22405780
TI  - Effect of co-solute and gelation temperature on milk protein and gum tragacanth
      interaction in acidified gels.
AB  - The aim of this study was to investigate the role of process conditions and
      system composition on the acid-induced gelation of a mixture of milk protein and
      gum tragacanth. This was studied by determining the effects of co-solute
      (lactose) addition (3, 5 and 7%) and gelation temperature (25, 37 and 45 degrees
      C) on the mixture's rheological properties and microstructure using a combination
      of techniques including small-deformation rheology and scanning electron
      microscopy. The presence of lactose played an important role in the
      microstructure formation of gels but did not change most rheological properties.
      The microstructure of gels formed in the presence of lactose was coarser and more
      particulate, but less interconnected; this can be explained by lactose's role in
      improving protein aggregation. Gels prepared at a lower temperature had a high
      structure strength, as indicated by their high storage modulus, tau(f) and G(f)
      values. Low gelation temperature also caused a more branched and homogenous
      microstructure.

PMID- 22405781
TI  - Inflammatory bowel diseases audited.

PMID- 22405782
TI  - Demanding dignity, and competence, in older people's care.

PMID- 22405783
TI  - Will Liberal Democrats take the chance to kill the Health Bill?

PMID- 22405784
TI  - Stem cell based therapy--where are we going?

PMID- 22405786
TI  - Paolo Macchiarini: crossing frontiers.

PMID- 22405787
TI  - Loss of life after evacuation: lessons learned from the Fukushima accident.

PMID- 22405788
TI  - Cardiac stem cells in patients with ischaemic cardiomyopathy.

PMID- 22405790
TI  - Cardiac stem cells in patients with ischaemic cardiomyopathy.

PMID- 22405791
TI  - Comparative efficacy of anti-manic drugs in acute mania.

PMID- 22405792
TI  - Comparative efficacy of anti-manic drugs in acute mania.

PMID- 22405793
TI  - Comparative efficacy of anti-manic drugs in acute mania.

PMID- 22405794
TI  - Comparative efficacy of anti-manic drugs in acute mania.

PMID- 22405796
TI  - Towards regenerative therapy for cardiac disease.
AB  - Development of regenerative therapeutic strategies to reverse the progression of
      advanced heart failure is one of the most urgent clinical needs of this century.
      Insights gained from clinical trials of adult stem cells, together with
      fundamental scientific advances in cardiac stem cell and regenerative biology,
      are beginning to yield potential new targets and strategies for regenerative
      therapies. Of particular importance are new scientific discoveries related to
      intrinsic cardiac regeneration, renewal factors that can trigger regeneration,
      and tissue-engineering technology, which are beginning to change the way
      investigators view the scientific and clinical position of cardiovascular
      regenerative therapy.

PMID- 22405797
TI  - Engineered whole organs and complex tissues.
AB  - End-stage organ failure is a key challenge for the medical community because of
      the ageing population and the severe shortage of suitable donor organs available.
      Equally, injuries to or congenital absence of complex tissues such as the
      trachea, oesophagus, or skeletal muscle have few therapeutic options. A new
      approach to treatment involves the use of three-dimensional biological scaffolds
      made of allogeneic or xenogeneic extracellular matrix derived from non-autologous
      sources. These scaffolds can act as an inductive template for functional tissue
      and organ reconstruction after recellularisation with autologous stem cells or
      differentiated cells. Such an approach has been used successfully for the repair
      and reconstruction of several complex tissues such as trachea, oesophagus, and
      skeletal muscle in animal models and human beings, and, guided by appropriate
      scientific and ethical oversight, could serve as a platform for the engineering
      of whole organs and other tissues.

PMID- 22405798
TI  - Rheumatic heart disease.
AB  - Rheumatic heart disease, often neglected by media and policy makers, is a major
      burden in developing countries where it causes most of the cardiovascular
      morbidity and mortality in young people, leading to about 250,000 deaths per year
      worldwide. The disease results from an abnormal autoimmune response to a group A
      streptococcal infection in a genetically susceptible host. Acute rheumatic fever-
      the precursor to rheumatic heart disease--can affect different organs and lead to
      irreversible valve damage and heart failure. Although penicillin is effective in
      the prevention of the disease, treatment of advanced stages uses up a vast amount
      of resources, which makes disease management especially challenging in emerging
      nations. Guidelines have therefore emphasised antibiotic prophylaxis against
      recurrent episodes of acute rheumatic fever, which seems feasible and cost
      effective. Early detection and targeted treatment might be possible if
      populations at risk for rheumatic heart disease in endemic areas are screened. In
      this setting, active surveillance with echocardiography-based screening might
      become very important.

PMID- 22405799
TI  - Sudden shock from capillary leak.

PMID- 22405800
TI  - The path from bench to bedside also requires ethics.

PMID- 22405801
TI  - The long and winding road for the Fukushima nuclear workers.

PMID- 22405802
TI  - The effects of starvation on digestive tract function and structure in juvenile
      southern catfish (Silurus meridionalis Chen).
AB  - The size and functional capacity of the gastrointestinal (GI) tract and
      associated organs vary in response to environmental cues. The GI tract and
      associated organs are also very metabolically active in animals. Hence, animals
      may reduce the size and function of their GI tract to conserve energy when
      deprived of food. The main aims of this study were to investigate how Silurus
      meridionalis regulates the function and structure of its GI tract and associated
      organs during starvation. Starvation induced a decrease in both maintenance
      metabolism (MO(2rest), decreased by approximately 50%) and respiratory frequency
      (indicated by double side gill activity and notated as f(R), decreased by 29%).
      Lipase, trypsin and aminopeptidase-A showed a similar reduction in mass-specific
      activities during starvation, but pepsin and alpha-amylase did not. The
      starvation of experimental fish resulted in a significant reduction in body
      weight, the wet mass of the liver and the digestive-somatic system, the hepato
      somatic index and the condition factor whereas the wet masses of the GI tract,
      pancreas, gall bladder and the relative intestinal length did not vary
      significantly during starvation. The reduction in liver wet mass was the main
      reason for the decrease in the wet mass of digestive-somatic system in this
      species. Only the mucosal area of the PI was affected significantly by
      starvation, decreasing by 34% at the end of the experiment. S. meridionalis
      displayed a decreasing intestinal mucosal area towards the distal intestine, and
      this gradient was not affected by starvation. The morphology and structure of
      both the GI tract and the liver were greatly down-regulated, as indicated by
      decreases in liver cell size, the mucosal thickness of the stomach and intestine,
      the density of goblet cells and microvilli surface area (MVSA), implying that
      food deprivation greatly impaired the digestive and absorptive functions of the
      GI tract in S. meridionalis. When deprived of food, S. meridionalis can endure
      harsh periods of starvation and adaptively down-regulate the function and
      structure of the digestive tract with physiological and biochemical strategies.

PMID- 22405803
TI  - Thoughts turned into high-level commands: Proof-of-concept study of a vision
      guided robot arm driven by functional MRI (fMRI) signals.
AB  - Previous studies have demonstrated the possibility of using functional MRI to
      control a robot arm through a brain-machine interface by directly coupling
      haemodynamic activity in the sensory-motor cortex to the position of two axes.
      Here, we extend this work by implementing interaction at a more abstract level,
      whereby imagined actions deliver structured commands to a robot arm guided by a
      machine vision system. Rather than extracting signals from a small number of pre
      selected regions, the proposed system adaptively determines at individual level
      how to map representative brain areas to the input nodes of a classifier network.
      In this initial study, a median action recognition accuracy of 90% was attained
      on five volunteers performing a game consisting of collecting randomly positioned
      coloured pawns and placing them into cups. The "pawn" and "cup" instructions were
      imparted through four mental imaginery tasks, linked to robot arm actions by a
      state machine. With the current implementation in MatLab language the median
      action recognition time was 24.3s and the robot execution time was 17.7s. We
      demonstrate the notion of combining haemodynamic brain-machine interfacing with
      computer vision to implement interaction at the level of high-level commands
      rather than individual movements, which may find application in future fMRI
      approaches relevant to brain-lesioned patients, and provide source code
      supporting further work on larger command sets and real-time processing.

PMID- 22405804
TI  - Creating a GIS-based model of marine debris "hot spots" to improve efficiency of
      a lobster trap debris removal program.
AB  - Debris removal programs are combatting the accumulation of derelict fishing gear
      and other debris in marine habitats. We analyzed 5 years of lobster trap debris
      removal data in Biscayne National Park, Florida to assess removal efficiency and
      develop spatially-explicit mapping tools to guide future removals. We generated
      and validated debris "hot spots" maps that combined remotely-sensed data (i.e.
      benthic habitat type and bathymetry) with 862 locations of previous debris
      collection. Our hot spot models spatially depict regions of likely debris
      accumulation, reducing the search area by 95% (from 332 km(2) to 18 km(2)) and
      encompassing 100% of the validation sites. Our analyses indicate removal
      contractors using sub-surface towed divers enhanced debris recovery.
      Additionally, the quantity of debris removed did not decrease with increased
      efforts, suggesting that debris supply in situ exceeds removal efforts. We
      conclude with the importance of coupling analysis of ongoing debris removal
      programs with GIS technology to improve removal efforts.

PMID- 22405805
TI  - Estimates of sediment and nutrient loads in 10 major catchments draining to the
      Great Barrier Reef during 2006-2009.
AB  - The Great Barrier Reef (GBR) catchment area has been monitored simultaneously for
      sediment and nutrient exports from 10 priority catchments discharging into the
      GBR lagoon between 2006 and 2009. This allows GBR catchment-wide exports to be
      estimated and spatially compared within a discrete time-frame. Elevated levels of
      sediment and nutrient exports were recorded in all monitored catchments as
      compared to pre-European estimates, but vary around previous estimates of mean
      annual loads. During the period of monitoring, the Burdekin and Fitzroy
      catchments contributed the highest sediment and nutrient exports, however when
      loads were normalised for area, these catchments produced the lowest unit yields.
      In contrast, the highest yields were produced in the wetter and proportionately
      more intensively cultivated Johnstone, O'Connell, and Pioneer catchments
      particularly for dissolved nitrogens. This assessment offers the necessary
      scientific foundation for future monitoring, assessment, and management of
      sediment and nutrient loads entering the GBR.

PMID- 22405806
TI  - Heterogeneity in head and neck IMRT target design and clinical practice.
AB  - PURPOSE: To assess patterns of H&N IMRT practice with particular emphasis on
      elective target delineation. MATERIALS AND METHODS: Twenty institutions with
      established H&N IMRT expertise were solicited to design clinical target volumes
      for the identical H&N cancer case. To limit contouring variability, a primary
      tonsil GTV and ipsilateral level II node were pre-contoured. Participants were
      asked to accept this GTV, and contour their recommended CTV and PTV. Dose
      prescriptions, contouring time, and recommendations regarding chemotherapy were
      solicited. RESULTS: All 20 institutions responded. Remarkable heterogeneity in
      H&N IMRT design and practice was identified. Seventeen of 20 centers recommended
      treatment of bilateral necks whereas 3/20 recommended treatment of the
      ipsilateral neck only. The average CTV volume was 250 cm(3) (range 37-676 cm(3)).
      Although there was high concordance in coverage of ipsilateral neck levels II and
      III, substantial variation was identified for levels I, V, and the contralateral
      neck. Average CTV expansion was 4.1mm (range 0-15 mm). Eight of 20 centers
      recommended chemotherapy (cisplatin), whereas 12/20 recommended radiation alone.
      Responders prescribed on average 69 and 68 Gy to the tumor and metastatic node
      GTV, respectively. Average H&N target volume contouring time was 102.5 min (range
      60-210 min). CONCLUSION: This study identifies substantial heterogeneity in H&N
      IMRT target definition, prescription, neck treatment, and use of chemotherapy
      among practitioners with established H&N IMRT expertise. These data suggest that
      continued efforts to standardize and simplify the H&N IMRT process are desirable
      for the safe and effective global advancement of H&N IMRT practice.

PMID- 22405807
TI  - An evidence based review of proton beam therapy: the report of ASTRO's emerging
      technology committee.
AB  - Proton beam therapy (PBT) is a novel method for treating malignant disease with
      radiotherapy. The purpose of this work was to evaluate the state of the science
      of PBT and arrive at a recommendation for the use of PBT. The emerging technology
      committee of the American Society of Radiation Oncology (ASTRO) routinely
      evaluates new modalities in radiotherapy and assesses the published evidence to
      determine recommendations for the society as a whole. In 2007, a Proton Task
      Force was assembled to evaluate the state of the art of PBT. This report reflects
      evidence collected up to November 2009. Data was reviewed for PBT in central
      nervous system tumors, gastrointestinal malignancies, lung, head and neck,
      prostate, and pediatric tumors. Current data do not provide sufficient evidence
      to recommend PBT in lung cancer, head and neck cancer, GI malignancies, and
      pediatric non-CNS malignancies. In hepatocellular carcinoma and prostate cancer
      and there is evidence for the efficacy of PBT but no suggestion that it is
      superior to photon based approaches. In pediatric CNS malignancies PBT appears
      superior to photon approaches but more data is needed. In large ocular melanomas
      and chordomas, we believe that there is evidence for a benefit of PBT over photon
      approaches. PBT is an important new technology in radiotherapy. Current evidence
      provides a limited indication for PBT. More robust prospective clinical trials
      are needed to determine the appropriate clinical setting for PBT.

PMID- 22405808
TI  - Programmable segmented volumetric modulated arc therapy for respiratory
      coordination in pancreatic cancer.
AB  - We programmably divided long-arc volumetric modulated arc therapy (VMAT) into
      split short arcs, each taking less than 30s for respiratory coordination. The
      VMAT plans of five pancreatic cancer patients were modified; the short-arc plans
      had negligible dose differences and satisfied the 3%/3-mm gamma index on a
      MapCHECK-2 device.

PMID- 22405809
TI  - Primary motor cortex excitability is modulated with bimanual training.
AB  - Bimanual visuomotor movement has been shown to enhance cortical motor activity in
      both hemispheres, especially when movements require simultaneous activation of
      homologous muscle groups (in-phase movement). It is currently unclear if these
      adaptations are specific to motor preparatory areas or if they also involve
      changes in primary motor cortex (M1). The present study investigated the
      representation of wrist muscles within motor cortex before and following bimanual
      movement training that was in-phase, anti-phase with or without motor
      preparation. Motor evoked potentials (MEPs) for the extensor carpi radialis
      muscle (ECR) cortical territory were acquired and analyzed before and following
      bimanual movement. The cortical representation was quantified and compared in
      terms of spatial extent and MEP amplitude, in two different experiments involving
      distinct movement training types. In Experiment 1, participants performed
      bimanual wrist flexion/extension movements to targets which involved in-phase
      movements, either following a 2s preparation period (In-phase preparation), or
      without the preparation period (In-phase no preparation). In Experiment 2,
      training involved antagonist muscle groups activated simultaneously (Anti-phase)
      with the addition of the 2s preparation period. In-phase bimanual movement
      enhanced the spatial representation of ECR in M1, and did not show a difference
      in MEP amplitude of the cortical area. It may be that simultaneous activation of
      homologous M1 representations in both hemispheres, in combination with activity
      from premotor areas, leads to a greater increase in plasticity in terms of
      increased M1 spatial extent of trained muscles.

PMID- 22405810
TI  - Regional brain perfusion before and after treatment with methylphenidate may be
      associated with the G1287A polymorphism of the norepinephrine transporter gene in
      children with attention-deficit/hyperactivity disorder.
AB  - The noradrenergic system modulates attention and arousal. Dysregulation of the
      noradrenergic system may be involved in the pathophysiology of attention
      deficit/hyperactivity disorder (ADHD). This study intended to examine the
      differences in methylphenidate (MPH) treatment response and pre- and post
      treatment cerebral perfusion associated with the G1287A and -3081(A/T)
      polymorphisms of the norepinephrine transporter (NET) gene in ADHD children.
      Thirty-seven drug-naive ADHD children (8.9+/-1.8 years old, M=32, F=5) were
      genotyped. Next, baseline single-photon emission computed tomography (SPECT) and
      clinical assessments were carried out for ADHD subjects. After 8 weeks of MPH
      treatment, SPECT and clinical assessment were repeated. There were no differences
      in baseline clinical assessments or cerebral perfusion based on genotype.
      However, after treatment, ADHD children with the G/G genotype at the G1287A
      polymorphism showed more improvement in symptoms than children without the G/G
      genotype as evaluated by the Clinical Global Impressions-Improvement scale
      (p=0.022). Furthermore, ADHD children with the G/G genotype at the G1287A
      polymorphism showed hyperperfusion in the right inferior temporal gyrus (p<0.001,
      uncorrected) and middle temporal gyrus (p=0.001, uncorrected) compared to
      children without the G/G genotype. Although the results of this study should be
      interpreted cautiously, they suggest that polymorphisms of the NET gene may
      contribute to an intermediate phenotype. Further studies should clearly elucidate
      the relationship between treatment response and functional connectivity in the
      brain according to this genetic polymorphism.

PMID- 22405811
TI  - Lower serum UA levels in Parkinson's disease patients in the Chinese population.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease in
      the world, and oxidative stress plays an important role in its pathogenesis. Uric
      acid (UA) is a product of purine metabolism and is a natural antioxidant that can
      relieve the oxidative stress that occurs in PD. Recent studies have indicated
      that the serum UA level are associated with a risk of PD and PD progression of
      motor symptoms and have proposed UA as a possible biomarker of the underlying
      pathophysiology of PD. In our study, we investigated the association between
      serum UA level and PD in a Chinese population. We found that the serum UA levels
      in PD patients were lower than the levels in control patients and were correlated
      with PD progression and duration in the Chinese population. These associations
      were observed in both genders, but hyperuricemia is more strongly associated with
      lower rates of PD among men compared to women and older people compared to
      younger people. Our results indicate that UA could be an important biomarker of
      PD and that the serum UA level could be a useful biomarker of PD diagnosis and
      disease progression.

PMID- 22405812
TI  - Chronic hypoxia and low salinity impair anti-predatory responses of the green
      lipped mussel Perna viridis.
AB  - The effects of chronic hypoxia and low salinity on anti-predatory responses of
      the green-lipped mussel Perna viridis were investigated. Dissolved oxygen
      concentrations ranged from hypoxic to normoxic (1.5 +/- 0.3 mg l(-1), 3.0 +/- 0.3
      mg l(-1) and 6.0 +/- 0.3 mg l(-1)), and salinities were selected within the
      variation during the wet season in Hong Kong coastal waters (150/00, 200/00,
      250/00 and 300/00). The dissolved oxygen and salinity significantly affected some
      anti-predatory responses of mussel, including byssus production, shell thickness
      and shell weight, and the adductor diameter was only significantly affected by
      salinity. Besides, interactive effects of dissolved oxygen and salinity on the
      byssus production and shell thickness were also observed. In hypoxic and low
      salinity conditions, P. viridis produced fewer byssal threads, thinner shell and
      adductor muscle, indicating that hypoxia and low salinity are severe
      environmental stressors for self-defence of mussel, and their interactive effects
      further increase the predation risk.

PMID- 22405813
TI  - Surgical management of nasal obstruction.
AB  - The proper evaluation of the patient with nasal obstruction relies on a
      comprehensive history and physical examination. Once the site of obstruction is
      accurately identified, the patient may benefit from a trial of medical
      management. At times however, the definitive treatment of nasal obstruction
      relies on surgical management. Recognizing the nasal septum, nasal valve, and
      turbinates as possible sites of obstruction and addressing them accordingly can
      dramatically improve a patient's nasal breathing. Conservative resection of
      septal cartilage, submucous reduction of the inferior turbinate, and structural
      grafting of the nasal valve when appropriate will provide the optimal improvement
      in nasal airflow and allow for the most stable results.

PMID- 22405814
TI  - Evolution of mitochondrial-encoded cytochrome oxidase subunits in endothermic
      fish: the importance of taxon-sampling in codon-based models.
AB  - While endothermy is ubiquitous in birds and mammals, it is not exclusive to these
      most recently arisen vertebrate classes. The ability to warm specific organs
      and/or tissues above ambient temperature (regional endothermy) has evolved at
      least three times in phylogentically discrete fish lineages: lamnid sharks
      (Lamnidae), tunas (Scombridae) and billfishes (Istiophoridae and Xiphidae). Given
      the links between endothermy and metabolic rate, we looked for evidence of
      convergent molecular evolution in mtDNA-encoded cytochrome c oxidase (COX)
      subunits in each of these discrete lineages. We found no evidence that the
      endothermic phenotype in fishes is driven or accompanied by molecular
      convergence. Though we found little evidence for positively-selected sites in any
      of the lineages in any subunit, the conclusions were sensitive to the choice of
      maximum-likelihood model. Several sites identified by Naive Empirical Bayes (NEB)
      were not found when Bayes Empirical Bayes (BEB) was employed. As well,
      conclusions were profoundly influenced by taxon-sampling. Several of the putative
      sites of positive selection in COX II were no longer apparent as we augmented
      taxon sampling. The lack of convergent molecular evolution in these remarkable
      taxa, combined with the profound influence of model choice and taxon sampling
      provide a cautionary note on the use of rates of non-synonymous to synonymous
      mutations (dN/dS) to explore questions of the evolution of physiological
      function.

PMID- 22405815
TI  - Gene turnover and differential retention in the relaxin/insulin-like gene family
      in primates.
AB  - The relaxin/insulin-like gene family is related to the insulin gene family, and
      includes two separate types of peptides: relaxins (RLNs) and insulin-like
      peptides (INSLs) that perform a variety of physiological roles including
      testicular descent, growth and differentiation of the mammary glands, trophoblast
      development, and cell differentiation. In vertebrates, these genes are found on
      three separate genomic loci, and in mammals, variation in the number and nature
      of genes in this family is mostly restricted to the Relaxin Family Locus B. For
      example, this locus contains a single copy of RLN in platypus and opossum,
      whereas it contains copies of the INSL6, INSL4, RLN2 and RLN1 genes in human and
      chimp. The main objective of this research is to characterize changes in the size
      and membership composition of the RLN/INSL gene family in primates, reconstruct
      the history of the RLN/INSL genes of primates, and test competing evolutionary
      scenarios regarding the origin of INSL4 and of the duplicated copies of the RLN
      gene of apes. Our results show that the relaxin/INSL-like gene family of primates
      has had a more dynamic evolutionary history than previously thought, including
      several examples of gene duplications and losses which are consistent with the
      predictions of the birth-and-death model of gene family evolution. In particular,
      we found that the differential retention of relatively old paralogs played a key
      role in shaping the gene complement of this family in primates. Two examples of
      this phenomenon are the origin of the INSL4 gene of catarrhines (the group that
      includes Old World monkeys and apes), and of the duplicate RLN1 and RLN2 paralogs
      of apes. In the case of INSL4, comparative genomics and phylogenetic analyses
      indicate that the origin of this gene, which was thought to represent a
      catarrhine-specific evolutionary innovation, is as old as the split between
      carnivores and primates, which took place approximately 97 million years ago. In
      addition, in the case of the RLN1 and RLN2 genes of apes our phylogenetic trees
      and topology tests indicate that the duplication that gave rise to these two
      genes maps to the last common ancestor of anthropoid primates. All these genomic
      changes in gene complement, which are particularly prevalent among anthropoid
      primates, might be linked to the many physiological and anatomical changes found
      in this group. Given the various roles of members of the RLN/INSL-like gene
      family in reproductive biology, it might be that changes in this gene family are
      associated to changes in reproductive traits.

PMID- 22405816
TI  - 'Hot feet - hot brain': gene and brain dysfunction in erythromelalgia.

PMID- 22405817
TI  - The impact of WIC food package changes on access to healthful food in 2 low
      income urban neighborhoods.
AB  - OBJECTIVE: To evaluate the impact of the 2009 food package changes for the
      Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) on
      the availability of healthful food. DESIGN: Survey of all food stores in the
      study area before and after the changes were implemented. SETTING: Two low-income
      neighborhoods in Philadelphia, 1 predominantly African-American, the other
      predominantly Hispanic. PARTICIPANTS: One hundred forty one supermarkets, grocery
      stores, and non-chain corner stores identified through field enumeration. MAIN
      OUTCOME MEASURES: Nutrition Environment Measure Survey for Stores (NEMS-S) to
      determine availability, price, and quality of fruit, vegetables, milk, cereal,
      beans, canned fish, meat, whole grains, and juice. ANALYSIS: Comparison of NEMS-S
      scores before and after food package changes using t tests and ordinary least
      squares regression to understand the role of supermarket status, WIC
      participation, and racial and income composition in predicting NEMS-S scores;
      geographic information systems to calculate proximity of residents to food
      stores. RESULTS: The availability of healthful food increased significantly in
      stores, overall, with more substantial increases in WIC-authorized stores.
      Supermarket status, WIC retail status, and NEMS-S scores at baseline were
      significant predictors of NEMS-S scores after the food package changes.
      CONCLUSIONS AND IMPLICATIONS: Changes in the WIC food package were associated
      with increased availability of healthful food in 2 low-income neighborhoods.

PMID- 22405818
TI  - The PIP mammary prosthesis: a product recall study.
AB  - INTRODUCTION: Concerns about the durability of silicone breast implants
      manufactured by Poly Implant Prothese (PIP) have been expressed for several years
      prior to their formal withdrawal from the market in March 2010. Although precise
      details of what elements were at fault remain unclear, concerns have been raised
      about both the elastomer and the filler gel. Media speculation has focussed on
      device safety, longevity and, recently, a possible association with lymphoma,
      specifically anaplastic large cell lymphoma (ALCL). There is however, no actual
      data concerning these implants with which to guide and inform when concerned
      patients seek advice. PATIENTS AND METHODS: PIP mammary prostheses were used by
      the senior author for both primary and revision breast augmentation (BA) during
      the period January 2000-August 2005. A database of patients was constructed and
      attempts made to contact each patient offering a free consultation and referral
      for ultrasound scan (USS). Chief outcome measures included secondary surgery, the
      implant rupture rate and time to rupture. RESULTS: 453 consecutive patients with
      PIP devices were identified. Of this number 30 had already undergone implant
      exchange for a variety of reasons. 180 (39.7%) could not be contacted and 19 had
      undergone explantation elsewhere, including the NHS. Of those who could be
      contacted, 47 declined consultation as they had no concerns. 97 had neither
      clinical signs nor radiographic evidence of implant rupture and elected to remain
      under regular review. At the time of writing, 38 have undergone implant exchange
      after ultrasonographic indication of rupture and the overall patient rupture rate
      for the PIP implant is 15.9-33.8%. This cohort correlates reduced implant
      longevity with each successive year from 2000 and no cases of ALCL have been
      diagnosed. DISCUSSION: Long-term studies such as this are difficult to undertake
      for a number of reasons as they place a significant additional burden of
      resources on a practice. They are, however, essential from an industry
      perspective both for the provision of information and supporting audit and
      professional standing. Being only a single-handed practice, this initial study is
      the tip of an iceberg that may affect 40,000 women in the UK with PIP implants,
      but it does provide some hard data with which to guide our patients. It is also
      believed to be the first independent product recall study in aesthetic breast
      surgery.

PMID- 22405819
TI  - Effect of shear stress, statins and TNF-alpha on hemostatic genes in human
      endothelial cells.
AB  - Atherosclerotic plaque formation and progression are dependent on local shear
      stress patterns and inflammatory cytokines. Statins effectively reduce the
      progression of atherosclerosis and the incidence of cardiovascular events.
      However, the benefit of statins cannot be explained by cholesterol reduction
      alone. This study, investigated the non-lipid lowering effects of simvastatin and
      rosuvastatin on endothelial anti- and prothrombotic genes under different
      biomechanical and inflammatory stress conditions. Endothelial cells responded in
      a similar way to simvastatin and rosuvastatin. However, they were more sensitive
      to simvastatin. The statins had anti-inflammatory properties counteracting the
      TNF-alpha effect on the hemostatic genes studied. There was no observed
      synergistic effect between shear stress and simvastatin. Simvastatin had a
      counteracting effect on t-PA and PAI-1 compared to TNF-alpha and shear stress.
      Simvastatin blocked the TNF-alpha suppressive effect on thrombomodulin and eNOS,
      irrespective of shear stress. The strong inductive effect of TNF-alpha on VCAM-1
      was counteracted by simvastatin and shear stress in an additive dose-response
      dependent way.

PMID- 22405820
TI  - Hyperpolarization-activated cation current Ih of dentate gyrus granule cells is
      upregulated in human and rat temporal lobe epilepsy.
AB  - The hyperpolarization-activated cation current I(h) is an important regulator of
      neuronal excitability and may contribute to the properties of the dentate gyrus
      granule (DGG) cells, which constitute the input site of the canonical hippocampal
      circuit. Here, we investigated changes in I(h) in DGG cells in human temporal
      lobe epilepsy (TLE) and the rat pilocarpine model of TLE using the patch-clamp
      technique. Messenger-RNA (mRNA) expression of I(h)-conducting HCN1, 2 and 4
      isoforms was determined using semi-quantitative in-situ hybridization. I(h)
      density was ~1.8-fold greater in DGG cells of TLE patients with Ammon's horn
      sclerosis (AHS) as compared to patients without AHS. The magnitude of
      somatodendritic I(h) was enhanced also in DGG cells in epileptic rats, most
      robustly during the latent phase after status epilepticus and prior to the
      occurrence of spontaneous epileptic seizures. During the chronic phase, I(h) was
      increased ~1.7-fold. This increase of I(h) was paralleled by an increase in HCN1
      and HCN4 mRNA expression, whereas HCN2 expression was unchanged. Our data
      demonstrate an epilepsy-associated upregulation of I(h) likely due to increased
      HCN1 and HCN4 expression, which indicate plasticity of I(h) during
      epileptogenesis and which may contribute to a compensatory decrease in neuronal
      excitability of DGG cells.

PMID- 22405821
TI  - Up-regulation of the betaine/GABA transporter BGT1 by JAK2.
AB  - Janus-activated kinase-2 JAK2 is activated by hyperosmotic shock and modifies the
      activity of several Na(+) coupled transporters. Carriers up-regulated by osmotic
      shock include the Na(+) coupled osmolyte transporter BGT1 (betaine/GABA
      transporter 1), which accomplishes the concentrative cellular uptake of gamma
      amino-butyric acid (GABA). The present study thus explored whether JAK2
      participates in the regulation of BGT1 activity. To this end, cRNA encoding BGT1
      was injected into Xenopus oocytes with or without cRNA encoding wild type JAK2,
      constitutively active (V617F)JAK2 or inactive (K882E)JAK2, and electrogenic GABA
      transport determined by dual electrode voltage clamp. In oocytes injected with
      cRNA encoding BGT1 but not in oocytes injected with water or with cRNA encoding
      JAK2 alone, the addition of 1mM GABA to the extracellular fluid generated an
      inward current (I(BGT)). In BGT1 expressing oocytes I(BGT) was significantly
      increased by coexpression of JAK2 or (V617F)JAK2, but not by coexpression of
      (K882E)JAK2. According to kinetic analysis coexpression of JAK2 increased the
      maximal I(BGT) without significantly modifying the concentration required for
      halfmaximal I(BGT) (K(M)). In oocytes expressing BGT1 and (V617F)JAK2 I(BGT) was
      gradually decreased by JAK2 inhibitor AG490 (40 MUM). The decline of I(BGT)
      following disruption of carrier insertion with brefeldin A (5 MUM) was similar in
      the absence and presence of the JAK2 inhibitor AG490 (40 MUM). In conclusion,
      JAK2 is a novel regulator of the GABA transporter BGT1. The kinase up-regulates
      the carrier presumably by enhancing the insertion of carrier protein into the
      cell membrane.

PMID- 22405822
TI  - Effect of angiotensin II on proliferation and differentiation of mouse induced
      pluripotent stem cells into mesodermal progenitor cells.
AB  - Previous studies suggest that angiotensin receptor stimulation may enhance not
      only proliferation but also differentiation of undifferentiated stem/progenitor
      cells. Therefore, in the present study, we determined the involvement of the
      angiotensin receptor in the proliferation and differentiation of mouse induced
      pluripotent stem (iPS) cells. Stimulation with angiotensin II (Ang II)
      significantly increased DNA synthesis in mouse iPS cells cultured in a medium
      with leukemia inhibitory factor (LIF). Pretreatment of the cells with either
      candesartan (a selective Ang II type 1 receptor [AT(1)R] antagonist) or Tempol (a
      cell-permeable superoxide scavenger) significantly inhibited Ang II-induced DNA
      synthesis. Treatment with Ang II significantly increased JAK/STAT3
      phosphorylation. Pretreatment with candesartan significantly inhibited Ang II-
      induced JAK/STAT3 phosphorylation. In contrast, induction of mouse iPS cell
      differentiation into Flk-1-positive mesodermal progenitor cells was performed in
      type IV collagen (Col IV)- coated dishes in a differentiation medium without LIF.
      When Col IV-exposed iPS cells were treated with Ang II for 5days, the expression
      of Flk-1 was significantly increased compared with that in the cells treated with
      the vehicle alone. Pretreatment of the cells with both candesartan and SB203580
      (a p38 MAPK inhibitor) significantly inhibited the Ang II- induced increase in
      Flk-1 expression. Treatment with Ang II enhanced the phosphorylation of p38 MAPK
      in Col IV- exposed iPS cells. These results suggest that the stimulation of mouse
      iPS cells with AT(1)R may enhance LIF-induced DNA synthesis, by augmenting the
      generation of superoxide and activating JAK/STAT3, and that AT(1)R stimulation
      may enhance Col IV-induced differentiation into mesodermal progenitor cells via
      p38 MAPK activation.

PMID- 22405823
TI  - Suppression of Arabidopsis RING-DUF1117 E3 ubiquitin ligases, AtRDUF1 and
      AtRDUF2, reduces tolerance to ABA-mediated drought stress.
AB  - Among approximately 480 RING domain-containing E3 Ub ligases in Arabidopsis,
      three, At3g46620, At5g59550, and At2g39720, have a domain-of-unknown-function
      (DUF) 1117 motif in their C-terminal regions. At3g46620 and At5g59550 were
      identified as homologous ABA- and drought-induced RING-DUF1117 genes and were
      designated AtRDUF1 and AtRDUF2, respectively. Single and double knock-out
      mutations of AtRDUFs resulted in hyposensitive phenotypes toward ABA in terms of
      germination rate and stomatal closure and markedly reduced tolerance to drought
      stress relative to wild-type plants. These results are discussed in the context
      that AtRDUF1 and AtRDUF2 play combinatorial, but still distinguishable, roles in
      ABA-mediated dehydration stress responses.

PMID- 22405825
TI  - LIMK2d, a truncated isoform of Lim kinase 2 regulates neurite growth in absence
      of the LIM kinase domain.
AB  - Lim kinase 2 isoforms, LIMK2a and LIMK2b, phosphorylate cofilin leading to
      remodeling of actin cytoskeleton during neuronal differentiation. The expression
      and function of the LIMK2d isoform, missing the kinase domain, remain unknown. We
      analyzed the expression of LIMK2 splice variants in adult rat brain and in
      cultures of rat neural stem cells by RT-QPCR. All three splice variants were
      expressed in adult cortex, hippocampus and cerebellum. Limk2a and Limk2d
      expression, but not Limk2b, increased during neuronal differentiation. We studied
      the localization and function of LIMK2d isoform by transfecting Hela, NSC-34, and
      hippocampal rat neuron cultures. Similarly to LIMK2b, LIMK2d was expressed in the
      cytoplasm, neurites and dendritic spines, but not in the nucleus. Similarly to
      LIMK2a, LIMK2d over-expression in NSC-34 cells increased neurite length, but
      independently of cofilin phosphorylation or of direct interaction with actin.
      Overall, these results indicate that LIMK2d is a third LIMK2 isoform which
      regulates neurite extension and highlights the possible existence of a kinase
      independent function of LIMK2.

PMID- 22405824
TI  - Desipramine selectively potentiates norepinephrine-elicited ERK1/2 activation
      through the alpha2A adrenergic receptor.
AB  - The precise physiological effects of antidepressant drugs, and in particular
      their actions at non-monoamine transporter targets, are largely unknown. We have
      recently identified the tricyclic antidepressant drug desipramine (DMI) as a
      direct ligand at the alpha(2A) adrenergic receptor (AR) without itself driving
      heterotrimeric G protein/downstream effector activation [5]. In this study, we
      report our novel finding that DMI modulates alpha(2A)AR signaling in response to
      the endogenous agonist norepinephrine (NE). DMI acted as a signaling potentiator,
      selectively enhancing NE-induced alpha(2A)AR-mediated ERK1/2 MAPK signaling. This
      potentiation of ERK1/2 activation was observed as an increase in NE response
      sensitivity and a prolongation of the activation kinetics. DMI in a
      physiologically relevant ratio with NE effectively turned on ERK1/2 signaling
      that is lacking in response to physiological NE alone. Further, the DMI-induced
      ERK1/2 potentiation relied on heterotrimeric G(i/o) proteins and was arrestin
      independent. This modulatory effect of DMI on NE signaling provides novel insight
      into the effects of this antidepressant drug on the noradrenergic system which it
      regulates, insight which enhances our understanding of the therapeutic mechanism
      for DMI.

PMID- 22405826
TI  - Involvement of tristetraprolin in transcriptional activation of hepatic 3-hydroxy
      3-methylglutaryl coenzyme A reductase by insulin.
AB  - Several AU-rich RNA binding element (ARE) proteins were investigated for their
      possible effects on transcription of hepatic 3-hydroxy-3-methyglutaryl coenzyme A
      reductase (HMGR) in normal rats. Using in vivo electroporation, four different
      siRNAs to each ARE protein were introduced together with HMGR promoter (-325 to
      +20) luciferase construct and compared to saline controls. All four siRNAs to
      tristetraprolin (TTP) completely eliminated transcription from the HMGR promoter
      construct. Since insulin acts to rapidly increase hepatic HMGR transcription, the
      effect of TTP siRNA on induction by insulin was tested. The 3-fold stimulation by
      insulin was eliminated by this treatment. In comparison, siRNA to AU RNA binding
      protein/enoyl coenzyme A hydratase (AUH) had no effect. These findings indicate a
      role for TTP in the insulin-mediated activation of hepatic HMGR transcription.

PMID- 22405827
TI  - Short-time glucose exposure of embryonic carcinoma cells impairs their function
      as terminally differentiated cardiomyocytes.
AB  - The fetal and postnatal phenotype is influenced by developmental conditions
      experienced prenatally. Among prenatal development metabolic factors are of
      particular importance as they are supposed to predispose for pathophysiological
      alterations later in life and to pioneer functional impairment in senescence
      (metabolic programming). Till now the mechanisms of metabolic programming are not
      well understood. We have investigated various concentrations of glucose during
      differentiation of pluripotent P19 embryonic carcinoma cells (ECC) into
      cardiomyocytes. Undifferentiated P19 cells were exposed to 5mM (low), 25 mM
      (control), 40 mM or 100mM (high) glucose for 48 h during embryoid body (EB)
      formation, followed by plating and differentiation into cardiomyocytes in vitro
      with standard glucose supplementation (25 mM) for 10-15 days. The amount of
      cardiac clusters, the frequency of spontaneous beatings as well as the expression
      of metabolic and cardiac marker genes and their promoter methylation were
      measured. We observed a metabolic programming effect of glucose during cardiac
      differentiation. Whereas the number of beating clusters and the expression of the
      cardiac marker alpha myosin heavy chain (alpha-MHC) were comparable in all
      groups, the frequencies of beating clusters were significantly higher in the high
      glucose group compared to low glucose. However, neither the insulin receptor (IR)
      or insulin like growth factor 1 receptor (IGF1R) nor the metabolic gene glucose
      transporter 4 (GLUT4) were influenced in RNA expression or in promoter
      methylation. Our data indicate that a short time glucose stress during embryonic
      cell determination leads to lasting effects in terminally differentiated cell
      function.

PMID- 22405828
TI  - Increases thermal stability and cellulose-binding capacity of Cryptococcus sp. S
      2 lipase by fusion of cellulose binding domain derived from Trichoderma reesei.
AB  - To improve the thermal stability and cellulose-binding capacity of Cryptococcus
      sp. S-2 lipase (CSLP), the cellulose-binding domain originates from Trichoderma
      reesei cellobiohydrolase I was engineered into C-terminal region of the CSLP
      (CSLP-CBD). The CSLP and CSLP-CBD were successfully expressed in the Pichia
      pastoris using the strong methanol inducible alcohol oxidase 1 (AOX1) promoter
      and the secretion signal sequence from Saccharomyces cerevisiae (alpha factor).
      The recombinant CSLP and CSLP-CBD were secreted into culture medium and estimated
      by SDS-PAGE to be 22 and 27 kDa, respectively. The fusion enzyme was stable at 80
      degrees C and retained more than 80% of its activity after 120-min incubation at
      this temperature. Our results also found that the fusion of fungal exoglucanase
      cellulose-binding domain to CSLP is responsible for cellulose-binding capacity.
      This attribute should make it an attractive applicant for enzyme immobilization.

PMID- 22405829
TI  - A guide to dosing in the treatment of cervical dystonia and blepharospasm with
      Xeomin(r): a new botulinum neurotoxin A.
AB  - Xeomin((r)) (incobotulinumtoxinA; Merz Pharmaceuticals, Frankfurt am Main,
      Germany) was first introduced in Germany for movement disorders in 2005. In 2010,
      it was approved for use in the United States by the FDA for the treatment of
      cervical dystonia (CD) and blepharospasm. It is a unique botulinum type A
      formulation free of any complexing proteins and contains only the pure 150 kD
      neurotoxin. Thus, the formation of neutralizing antibodies is not induced even
      after long-term treatment. The purpose of this report is to review the safety
      profile and dosing schedule for Xeomin for the treatment of CD and blepharospasm.
      The recommended dose for patients with CD is 120 U/treatment, with administration
      intervals normally between 3 and 6 months. However, clinical studies have found
      Xeomin to be safe and effective at doses up to 400 U in both previously treated
      and treatment-naive patients. The recommended starting dose in patients with
      blepharospasm is 2.5-5.0 U/injection site. Patients can be switched using a 1:1
      conversion ratio from Botox((r)) (onabotulinumtoxinA, Allergen Inc., Irvine, CA,
      USA) to Xeomin without any loss of efficacy or safety concerns. Xeomin does not
      differ from Botox in terms of its potency, onset, diffusion profile, or duration
      and waning of effect. It is the only botulinum treatment that is stable for up to
      3 years at room temperature. Xeomin offers a new and important treatment option
      for movement disorders.

PMID- 22405831
TI  - The first stereoselective total synthesis of (Z)-cryptomoscatone D2, a natural G2
      checkpoint inhibitor.
AB  - The first stereoselective synthesis of (Z)-cryptomoscatone D2, a naturally
      occurring G(2) checkpoint inhibitor, was accomplished using propane-1,3-diol as
      the starting material. The Maruoka asymmetric allylation, ring closing metathesis
      and the hydrogenation of the triple bond employing Lindlar's catalyst were
      involved as the key steps.

PMID- 22405830
TI  - Novel diabetes mellitus treatment: mature canine insulin production by canine
      striated muscle through gene therapy.
AB  - Muscle-targeted gene therapy using insulin genes has the potential to provide an
      inexpensive, low maintenance alternative or adjunctive treatment method for
      canine diabetes mellitus. A canine skeletal muscle cell line was established
      through primary culture, as well as through transdifferentiation of canine
      fibroblasts after infection with a myo-differentiation gene containing adenovirus
      vector. A novel mutant furin-cleavable canine preproinsulin gene insert (cppI4)
      was designed and created through de novo gene synthesis. Various cell lines,
      including the generated canine muscle cell line, were transfected with nonviral
      plasmids containing cppI4. Insulin and desmin immunostaining were used to prove
      insulin production by muscle cells and specific canine insulin ELISA to prove
      mature insulin secretion into the medium. The canine myoblast cultures proved
      positive on desmin immunostaining. All cells tolerated transfection with cppI4
      containing plasmid, and double immunostaining for insulin and desmin proved
      present in the canine cells. Canine insulin ELISA assessment of medium of cppI4
      transfected murine myoblasts and canine myoblast and fibroblast mixture proved
      presence of mature fully processed canine insulin, 24 and 48 h after
      transfection. The present study provides proof of principle that canine muscle
      cells can be induced to produce and secrete canine insulin on transfection with
      nonviral plasmid DNA containing a novel mutant canine preproinsulin gene that
      produces furin-cleavable canine preproinsulin. This technology could be developed
      to provide an alternative canine diabetes mellitus treatment option or to provide
      a constant source for background insulin, as well as C-peptide, alongside current
      treatment options.

PMID- 22405832
TI  - Discovery of nor-seco himbacine analogs as thrombin receptor antagonists.
AB  - Discovery of a novel nor-seco himbacine analog as potent thrombin receptor (PAR
      1) antagonist is described. Despite low plasma level, these new analogs showed
      excellent ex vivo efficacy in the monkey platelet aggregation assay. A potent
      hydroxy metabolite generated in vivo was identified as the agent responsible for
      the ex vivo efficacy. Following this discovery, the metabolite series was
      optimized to obtain analogs that showed very good ex vivo efficacy along with
      excellent pharmacokinetic profile in c. monkey.

PMID- 22405833
TI  - Thiadiazoles as new inhibitors of diacylglycerol acyltransferase type 1.
AB  - A novel class of DGAT1 inhibitors containing a thiadiazole core has been
      discovered. Chemical optimization lead to inhibitors of human DGAT1 with an
      appropriate ADME profile and that show in vivo activity in target tissues.

PMID- 22405834
TI  - Simple DNA transformation in Pseudomonas based on the Yoshida effect.
AB  - Current protocols of recombinant DNA research, including gene cloning and
      complementation, quantification of gene expression and tagging with reporter
      proteins, are usually limited by the availability of effective bacteria
      transformation tools different from Escherichia coli. This is particularly
      relevant with respect to the Pseudomonas species due to their biotechnological
      and sanitary importance. Here, we describe an optimized and efficient plasmid
      transference protocol based on the Yoshida effect, a method that relies on DNA
      uptake mediated by friction forces. The main advantages of this method are: (i)
      no competent cell preparation is needed, (ii) cells in any physiological state
      can be used, (iii) the procedure is performed directly on agar plates and (iv)
      the protocol, which is neither time-consuming nor labor-intensive, offers good
      efficiency. This approach promises to become the gold standard for day to day
      genetic manipulation in Pseudomonas.

PMID- 22405835
TI  - Gender differences in cigarette smoking, social correlates and cessation among
      adolescents.
AB  - BACKGROUND: Despite well-established gender differences in adult smoking
      behaviors, relatively little is known about gender discrepancies in smoking
      behaviors among adolescents, and even less is known about the role of gender in
      smoking cessation among teen populations. METHOD: The present study examined
      gender differences in a population of 755 adolescents seeking to quit smoking
      through the American Lung Association's Not-On-Tobacco (N-O-T) program. All
      participants enrolled in the N-O-T program between 1998 and 2009. All
      participants completed a series of questionnaires prior to and immediately
      following the cessation intervention. Analyses examined gender differences in a
      range of smoking variables, cessation success and direct and indirect effects on
      changes in smoking behaviors. RESULTS: Females were more likely to have parents,
      siblings and romantic partners who smokes, perceive that those around them will
      support a cessation effort, smoke more prior to intervention if they have friends
      who smoke, and to have lower cessation motivation and confidence if they have a
      parent who smokes. Conversely, males were more likely to have lower cessation
      motivation and confidence and be less likely to quit if they have a friend who
      smokes. CONCLUSIONS: Gender plays an important role in adolescent smoking
      behavior and smoking cessation. Further research is needed to understand how
      these differences may be incorporated into intervention design to increase
      cessation success rates among this vulnerable population of smokers.

PMID- 22405836
TI  - Vicious cycle in liver carcinogenesis: an epigenetic mirage.

PMID- 22405837
TI  - Structure-dependent activation of NR4A2 (Nurr1) by 1,1-bis(3'-indolyl)-1
      (aromatic)methane analogs in pancreatic cancer cells.
AB  - NR4A2 (Nurr1) is an orphan nuclear receptor with no known endogenous ligands and
      is highly expressed in many cancer cell lines including Panc1 and Panc28
      pancreatic cancer cells. Structure-dependent activation of NR4A2 by a series of
      1,1-bis(3'-indolyl)-1-(aromatic)methane (C-DIM) analogs was determined in
      pancreatic cancer cells transfected with yeast GAL4-Nurr1 chimeras and a UASx5
      luc reporter gene or constructs containing response elements that bind NR4A2.
      Among 23 different structural analogs, phenyl groups containing p-substituted
      trifluoromethyl, t-butyl, cyano, bromo, iodo and trifluoromethoxy groups were the
      most active compounds in transactivation assay. The p-bromophenyl analog (DIM-C
      pPhBr) was used as a model for structure-activity studies among a series of ortho
      , meta- and para-bromophenyl isomers and the corresponding indole 2- and N-methyl
      analogs. Results show that NR4A2 activation was maximal with the p-bromophenyl
      analog and methylation of the indole NH group abrogated activity. Moreover, using
      GAL4-Nurr1 (full length) or GAL-Nurr1-A/B and GAL4-Nurr1-(C-F) chimeras
      expressing N- and C-terminal domains of Nurr1, respectively, DIM-C-pPhBr
      activated all three constructs and these responses were differentially affected
      by kinase inhibitors. DIM-C-pPhBr also modulated expression of several Nurr1
      regulated genes in pancreatic cancer cells including vasoactive intestinal
      peptide (VIP), and the immunohistochemical and western blot analyses indicated
      that DIM-C-pPhBr activates nuclear NR4A2.

PMID- 22405838
TI  - The Toronto Western Spasmodic Torticollis Rating Scale: reliability in
      neurologists and physiotherapists.
AB  - INTRODUCTION: Inter-rater reliability for the Toronto Western Spasmodic
      Torticollis Rating Scale has been determined for neurologists, but not for
      physiotherapists. We assessed the inter-rater reliability of scoring the clinical
      severity subscale of the Toronto Western Spasmodic Torticollis Rating Scale by
      two physiotherapists and two neurologists. METHODS: Seven individuals with
      cervical dystonia were assessed on video a total of 23 times. The assessments
      were randomized and rated by all raters. RESULTS: Reliability for all raters
      considered together, assessed by the Intraclass Correlation Coefficient (ICC 2,1)
      was 0.74 (p < 0.001, 95% CI 0.46-0.88). Reliability for the two clinician groups
      was not significantly different: neurologists ICC (2,1) = 0.75 (p < 0.001, 95% CI
      0.44-0.89), physiotherapists ICC (2,1) = 0.82 (p < 0.001, 95% CI 0.30-0.94).
      CONCLUSION: The clinical severity subscale of the Toronto Western Spasmodic
      Torticollis Rating Scale can be assessed with good inter-rater reliability when
      physiotherapists and neurologists are represented in the same rater pool.

PMID- 22405839
TI  - Sensitivity and specificity of Addenbrooke's Cognitive Examination, Mattis
      Dementia Rating Scale, Frontal Assessment Battery and Mini Mental State
      Examination for diagnosing dementia in Parkinson's disease.
AB  - INTRODUCTION: Among the non-motor features of Parkinson's disease (PD), cognitive
      impairment is one of the most troublesome problems. Highly sensitive and specific
      screening instruments for detecting dementia in PD (PDD) are required in the
      clinical practice. METHODS: In our study we evaluated the sensitivity and
      specificity of different neuropsychological tests (Addenbrooke's Cognitive
      Examination, ACE; Frontal Assessment Battery, FAB and Mattis Dementia Rating
      Scale, MDRS) in 73 Parkinson's disease patients without depression. By receiver
      operating characteristic curve analysis, these screening instruments were tested
      against the recently established clinical diagnostic criteria of PDD. RESULTS:
      Best cut-off score for ACE to identify PDD was 80 points (sensitivity = 74.0%,
      specificity = 78.1%). For FAB the most optimal cut-off value was 12 points
      (sensitivity = 66.3%, specificity = 72.2%); whereas for MDRS it was 125 points
      (sensitivity = 89.8%, specificity = 98.3%). Among the examined test batteries,
      MDRS had the best clinicometric profile for detecting PDD. CONCLUSION: Although
      the types of applied screening instruments might differ from movement disorder
      clinic to clinic within a country, determination of the most specific and
      sensitive test for the given population remains to be an important task. Our
      results demonstrated that the specificity and sensitivity of MDRS was better than
      those of ACE, FAB and MMSE in Hungary. However, further studies with larger
      sample size and more uniform criteria for participation are required to determine
      the most suitable screening instrument for cognitive impairment.

PMID- 22405840
TI  - Lymphocytes as internal standard in oxidative burst analysis by cytometry: a new
      data analysis approach.
AB  - We propose a new data analysis approach for reactive oxygen species detection
      using Dihydrorhodamine 123 in blood monocytes and neutrophils. This approach,
      based on data transformation using lymphocytes as internal standard, allows to
      appreciate free radical production by monocytes also without Phorbol 12-myristate
      13-acetate (PMA) activation. In addition, this method is sensitive to differences
      in healthy subjects due to sub-pathological conditions, such as
      hypercholesterolemia.

PMID- 22405841
TI  - Detection of estradiol at an electrochemical immunosensor with a Cu UPD|DTBP
      Protein G scaffold.
AB  - A copper monolayer was formed on a gold electrode surface via underpotential
      deposition (UPD) method to construct a Cu UPD|DTBP-Protein G immunosensor for the
      sensitive detection of 17beta-estradiol. Copper UPD monolayer can minimize the
      non-specific adsorption of biological molecules on the immunosensor surface and
      enhance the binding efficiency between immunosensor surface and thiolated Protein
      G. The crosslinker DTBP (Dimethyl 3,3'-dithiobispropionimidate . 2HCl) has strong
      ability to immobilize Protein G molecules on the electrode surface and the
      immobilized Protein G provides an orientation-controlled binding of antibodies. A
      monolayer of propanethiol was firstly self-assembled on the gold electrode
      surface, and a copper monolayer was deposited via UPD on the propanethiol
      modified electrode. Propanethiol monolayer helps to stabilize the copper
      monolayer by pushing the formation and stripping potentials of the copper UPD
      monolayer outside the potential range in which copper monolayer can be damaged
      easily by oxygen in air. A droplet DTBP-Protein G was then applied on the
      modified electrode surface followed by the immobilization of estradiol antibody.
      Finally, a competitive immunoassay was conducted between estradiol-BSA (bovine
      serum albumin) conjugate and free estradiol for the limited binding sites of
      estradiol antibody. Square wave voltammetry (SWV) was employed to monitor the
      electrochemical reduction current of ferrocenemethanol and the SWV current
      decreased with the increase of estradiol-BSA conjugate concentration at the
      immunosensor surface. Calibration of immunosensors in waste water samples spiked
      with 17beta-estradiol yielded a linear response up to ~ 2200 pg mL(-1), a
      sensitivity of 3.20 MUA/pg mL(-1) and a detection limit of 12 pg mL(-1). The
      favorable characteristics of the immunosensors such as high selectivity,
      sensitivity and low detection limit can be attributed to the Cu UPD|DTBP-Protein
      G scaffold.

PMID- 22405842
TI  - A molecular machine biosensor: construction, predictive models and experimental
      studies.
AB  - This paper describes the construction, operation and predictive modeling of a
      molecular machine, functioning as a high sensitivity biosensor. Embedded
      gramicidin A (gA) ionchannels in a self-assembled tethered lipid bilayer act as
      biological switches in response to target molecules and provide a signal
      amplification mechanism that results in high sensitivity molecular detection. The
      biosensor can be used as a rapid and sensitive point of care diagnostic device in
      different media such as human serum, plasma and whole blood without the need for
      pre and post processing steps required in an enzyme-linked immunosorbent assay.
      The electrical reader of the device provides the added advantage of objective
      measurement. Novel ideas in the construction of the molecular machine, including
      fabrication of biochip arrays, and experimental studies of its ability to detect
      analyte molecules over a wide range of concentrations are presented. Remarkably,
      despite the complexity of the device, it is shown that the response can be
      predicted by modeling the analyte fluid flow and surface chemical reactions. The
      derived predictive models for the sensing dynamics also facilitate determining
      important variables in the design of a molecular machine such as the ion channel
      lifetime and diffusion dynamics within the bilayer lipid membrane as well as the
      bio-molecular interaction rate constants.

PMID- 22405843
TI  - Microelectrode array biosensor for studying carbohydrate-mediated interactions.
AB  - Carbohydrate-mediated host-pathogen interactions are essential to bacterial and
      viral pathogenesis, and represent an attractive target for the development of
      antiadhesives to prevent infection. We present a versatile microelectrode array
      based platform to investigate carbohydrate-mediated protein and bacterial
      binding, with the objective of developing a generalizable method for screening
      inhibitors of host-microbe interactions. Microelectrode arrays are well suited
      for interrogating biological binding events, including proteins and whole-cells,
      and are amenable to electrochemical derivitization, facilitating rapid deposition
      of biomolecules. In this study, we achieve microelectrode functionalization with
      carbohydrates via controlled polymerization of pyrrole to individual
      microelectrodes, followed by physisorption of neoglycoconjugates to the
      polypyrrole-coated electrodes. Bioactivity of the immobilized carbohydrates was
      confirmed with carbohydrate-binding proteins (lectins) detected by both
      fluorescent and electrochemical means. The platform's ability to analyze whole
      cell binding was demonstrated using strains of Escherichia coli and Salmonella
      enterica, and the dose-dependent inhibition of S. enterica by a soluble
      carbohydrate antiadhesive.

PMID- 22405844
TI  - Improvement of electrical blood hematocrit measurements under various plasma
      conditions using a novel hematocrit estimation parameter.
AB  - This paper presents an electrical method for measurement of Hematocrit (HCT)
      using a novel HCT estimation parameter. Particularly in the case of electrical
      HCT measurements, the measurement error generally increases with changes in the
      electrical conditions of the plasma such as conductivity and osmolality. This is
      because the electrical properties of blood are a function not only of HCT, but
      also of the electrical conditions in the plasma. In an attempt to reduce the
      measurement errors, we herein propose a novel HCT estimation parameter reflecting
      the characteristics of both the changes in volume of red blood cells (RBCs) and
      electrical conditions of plasma, simultaneously. In order to characterize the
      proposed methods under various electrical conditions of plasma, we prepared
      twelve blood samples such as four kinds of plasma conditions (hypotonic,
      isotonic, two kinds of hypertonic conditions) at three different HCT levels.
      Using linear regression analysis, we confirmed that the proposed parameter was
      highly correlated with reference HCT (HCT(ref.)) values measured by
      microcentrifugation. Thus, the HCT measurement error was less than 4%, despite
      considerable variations in the conductivity and osmolality of the plasma at
      conditions of the HCT(ref.) of 20%. Multiple linear regression analysis showed
      that the proposed HCT estimation parameter also yielded a lower measurement error
      (1%) than the other parameter previously used for the same purpose. Thus, these
      preliminary results suggest that proposed method could be used for accurate,
      fast, easy, and reproducible HCT measurements in medical procedures.

PMID- 22405845
TI  - Dehydration of crude protein from Ginkgo biloba L. by microwave freeze drying.
AB  - The paper optimized the parameters of microwave freeze drying (MFD) of crude
      Ginkgo biloba protein (CPG) using response surface methodology (RSM) based on the
      analysis of its proximate composition. The results showed that coefficients of
      determination, R(2) values for drying time and protein solubility were greater
      than 0.9500. The drying time and protein solubility of CPG varied curvilinearly
      with increase of microwave power and pre-freeze temperature, and drying time
      varied linearly with material thickness. The optimum MFD condition was microwave
      power of 408-421 W, material thickness of 15 mm and pre-freeze temperature of -20
      degrees C to -21 degrees C, respectively.

PMID- 22405846
TI  - Monolithic cryogels made of agarose-chitosan composite and loaded with agarose
      beads for purification of immunoglobulin G.
AB  - In order to obtain a novel absorbent with high adsorption capacity for the
      purification of immunoglobulin G (IgG), continuous supermacroporous agarose beads
      embedded agarose-chitosan composite monolithic cryogels (agarose-chitosan
      cryogels) were prepared by cryo-copolymerization of agarose-chitosan blend
      solutions with glutaraldehyde as the crosslinker in the presence of agarose
      beads. After coupling 2-mercaptopyridine onto divinylsulfone-activated matrix,
      the obtained cryogels were used for the purification of IgG. The microstructure
      morphologies of the cryogels were analyzed by scanning electron microscopy. The
      results showed that the obtained cryogels possess interconnected pores of 10-100
      MUm size. The specific surface area was 350 m(2)/g with maximum adsorption
      capacity of IgG 71.4 mg/g. The cryogels showed workable stability, and can be
      reused at least 15 times without significant loss in adsorption capacity. IgG
      purity after one-step purification from human plasma was monitored by
      electrophoresis and the average recovery was estimated to be 90%.

PMID- 22405847
TI  - Spectroscopic probing of recognition of the G-quadruplex in c-kit promoter by
      small-molecule natural products.
AB  - The c-kit oncogene plays important roles in cell growth and proliferation which
      is associated with many human tumors. In this study, electrospray ionization mass
      spectrometry (ESI-MS) and circular dichroism (CD) spectroscopy were used to
      evaluate the formation and recognition of the G-quadruplex by
      d(AGGGAGGGCGCTGGGAGGAGGG) in the promoter region of the c-kit oncogene. Among the
      twelve small natural molecules studied, three crescent-shaped small molecules
      (chelerythrine, jatrorrhizine and berberine, named as P1-P3) and one flexible
      cyclic small molecule (fangchinoline, named as P4) were found to bind to the G
      quadruplex with high affinities. The melting experiments demonstrate that P1-P4
      can significantly enhance the stability of the G-quadruplex with the ordering of
      P1~P4>P3>P2. Further insight into the binding mode of small molecules with the G
      quadruplex by Autodock3 analysis reveals that P1-P3 prefer the end-stacking mode
      with the G-quadruplex through pi-pi interaction and P4 prefers to insert into the
      groove outside the G-tetrads. Thus, our research finds that four ligands (P1-P4)
      from small natural molecules have high affinity to, and can significantly enhance
      the stability of the G-quadruplex in the promoter region of the c-kit oncogene.

PMID- 22405848
TI  - Biophysical control of invasive tumor cell behavior by extracellular matrix
      microarchitecture.
AB  - Fibrillar collagen gels, which are used extensively in vitro to study tumor
      microenvironment interactions, are composed of a cell-instructive network of
      interconnected fibers and pores whose organization is sensitive to polymerization
      conditions such as bulk concentration, pH, and temperature. Using confocal
      reflectance microscopy and image autocorrelation analysis to quantitatively
      assess gel microarchitecture, we show that additional polymerization parameters
      including culture media formulation and gel thickness significantly affect the
      dimensions and organization of fibers and pores in collagen gels. These findings
      enabled the development of a three-dimensional culture system in which cell-scale
      gel microarchitecture was decoupled from bulk gel collagen concentration.
      Interestingly, morphology and migration characteristics of embedded MDA-MB-231
      cells were sensitive to gel microarchitecture independently of collagen gel
      concentration. Cells adopted a polarized, motile phenotype in gels with larger
      fibers and pores and a rounded or stellate, less motile phenotype in gels with
      small fibers and pores regardless of bulk gel density. Conversely, cell
      proliferation was sensitive to gel concentration but not microarchitecture. These
      results indicate that cell-scale gel microarchitecture may trump bulk-scale gel
      density in controlling specific cell behaviors, underscoring the biophysical role
      of gel microarchitecture in influencing cell behavior.

PMID- 22405849
TI  - Salivary cortisol: a tool for biobehavioral research in children.

PMID- 22405850
TI  - Coupling inflammation with evo-devo.
AB  - Inflammation integrates diverse mechanisms that are associated not only with
      pathological conditions, such as cardiovascular diseases, type 2 diabetes,
      obesity, neurodegenerative diseases and cancer, but also with physiological
      processes like reproduction i.e. oogenesis and embryogenesis as well as aging. In
      the current review we firstly propose that the inflammatory response could
      recapitulate the phylogenia. In this way, highly conserved inflammatory
      mechanisms that play a main role in the evolutive development of different animal
      species, both invertebrates as well as vertebrates, are identified. Therefore, we
      also hypothesize that inflammation could represent a key tool used by nature to
      modulate organisms according to the environmental conditions in which these
      develop. Thus, inflammation could be the pathway by which the environmental
      factors could be related to the evolutionary development. If so, the diverse
      human chronic inflammatory diseases that nowadays the Western society suffer
      would represent the way for adapting to the abrupt changes in their lifestyle.
      Nonetheless, the distribution of the different pathological conditions varies in
      terms of intensity and magnitude among Western country populations depending on
      their genetic polymorphism. In this case, it should be considered that this set
      of diseases, distributed between all the individuals that constitute the
      Westernized society, would represent a true Social Inflammatory Syndrome whose
      final result is its remodeling. In this context, the use of inflammation by the
      Western society could represent the camouflaged expression of efficient
      mechanisms of evolution and development. In addition, if the different types of
      the inflammatory response involved in these diverse chronic pathological
      conditions could trace the biochemical origins of life, perhaps inflammation
      could represent an archaeological tool of unsuspected usefulness for
      understanding our own origin.

PMID- 22405851
TI  - p53-Independent expression of wild-type p53-induced phosphatase 1 (Wip1) in
      methylmethane sulfonate-treated cancer cell lines and human tumors.
AB  - Wild-type p53-induced phosphatase 1 (Wip1, PPM1D) is induced by p53 in response
      to various stressors and dephosphorylates cellular target proteins involved in
      DNA repair and cell cycle checkpoint pathways. The Wip1 gene is frequently
      amplified or overexpressed in human cancers, promoting tumor growth by switching
      off major checkpoint kinases and p53. To explore wild-type p53-independent Wip1
      induction, Wip1 promoter activity and its transcript level were evaluated by
      luciferase assay and real-time PCR, after methylmethane sulfonate (MMS) treatment
      in breast cancer cell lines and p53-null cell lines. Wip1 promoter activities in
      response to UV irradiation and various anti-cancer agents were compared between
      wild-type and a p53-response element (p53RE) mutated construct. Wip1 expression
      and its effects were examined in primary non-small cell lung cancer (NSCLC) and
      colon tumor cells by using Wip1-specific siRNA. MMS induced Wip1 promoter
      activity in Hs578T, MDA-MB-231, and SK-BR-3 cells expressing DNA binding
      deficient p53 mutants. A549-E6 and HCT116 (p53(-/-)) cells retained substantial
      Wip1 induction. Wip1 promoter activity was reduced, but not eliminated, in cells
      expressing a promoter containing a mutated p53-response element. Wip1 induction
      was not blocked by SB202190 or SP600125. MMS increased Wip1 expression in primary
      non-small cell lung cancer cells expressing a p53 R175H mutant. Our data indicate
      that Wip1 is induced in the absence of functional p53, like p38 MAPK and JNK, as
      a stress response terminator.

PMID- 22405852
TI  - Roles of c-Rel signalling in inflammation and disease.
AB  - Nuclear factor kappa B (NFkappaB) is a dimeric transcription factor comprised of
      five family members RelA (p65), RelB, c-Rel, p50 and p52. NFkappaB signalling is
      complex and controls a myriad of normal cellular functions. However, constitutive
      or aberrant activation of this pathway is associated with disease progression and
      cancer in multiple organs. The diverse array of biological responses is modulated
      by many factors, including the activating stimulus, recruitment of co-regulatory
      molecules, consensus DNA binding sequence, dimer composition and post
      translational modifications. Each subunit has very different biological functions
      and in the context of disease the individual subunits forming the NFkappaB dimer
      can have a profound effect, causing a shift in the balance from normal to
      pathogenic signalling. Here we discuss the role of c-Rel dependant signalling in
      normal physiology and its contribution to disease both inside and outside of the
      immune system.

PMID- 22405853
TI  - sHSP in the eye lens: crystallin mutations, cataract and proteostasis.
AB  - alpha-Crystallin, a major component of the eye lens cytoplasm, is a large
      multimer formed from two members of the small heat shock protein (sHsp) family.
      Inherited crystallin mutations are a common cause of childhood cataract, whereas
      miscellaneous changes to the long-lived crystallins cause age-related cataract,
      the most common cause of blindness worldwide. Newly formed eye lens cells use
      proteostasis to deal with the consequences of mutations, whereas mature lens
      cells, devoid of the ATP-driven folding and degradation machines, are
      hypothesized to have the alpha-crystallin "holdase" chaperone function to prevent
      protein aggregation. We discuss the impact of truncating and missense mutations
      on alpha-crystallin, based on recent progress towards determining sHsp 3D
      structure. Dominant missense mutations to the "alpha-crystallin domain" of alphaA
      (HSPB4) or alphaB-crystallin (HSPB5) occur on residues predicted to facilitate
      domain dynamics. alphaB-Crystallin is also expressed in striated muscle and
      mutations cause myopathy. The impact on these cellular cytoplasms is compared
      where sHsp multimer partners and metabolic constraints are different. Selected
      inherited mutations of the lens beta- and gamma-crystallins are considered in the
      context of their possible dependence on the "holdase" chaperone function of alpha
      crystallin. Looking at discrete changes to specific crystallin polypeptide chains
      that can function as chaperone or substrate provide insights into the workings of
      a cytoplasmic proteostatic system. These observations provide a framework for
      validating the function of alpha-crystallin as a chaperone, or as a lens space
      filler adapted from a chaperone function. Understanding the mechanistic role of
      alpha-crystallins will aid progress in research into age-related cataract and
      adult-onset myopathy. This article is part of a Directed Issue entitled: Small
      HSPs in physiology and pathology.

PMID- 22405854
TI  - Epinephrine deficiency results in intact glucose counter-regulation, severe
      hepatic steatosis and possible defective autophagy in fasting mice.
AB  - Epinephrine is one of the major hormones involved in glucose counter-regulation
      and gluconeogenesis. However, little is known about its importance in energy
      homeostasis during fasting. Our objective is to study the specific role of
      epinephrine in glucose and lipid metabolism during starvation. In our experiment,
      we subject regular mice and epinephrine-deficient mice to a 48-h fast then we
      evaluate the different metabolic responses to fasting. Our results show that
      epinephrine is not required for glucose counter-regulation: epinephrine-deficient
      mice maintain their blood glucose at normal fasting levels via glycogenolysis and
      gluconeogenesis, with normal fasting-induced changes in the peroxisomal
      activators: peroxisome proliferator activated receptor gamma coactivator alpha
      (PGC-1alpha), fibroblast growth factor 21 (FGF-21), peroxisome proliferator
      activated receptor alpha (PPAR-alpha), and sterol regulatory element binding
      protein (SREBP-1c). However, fasted epinephrine-deficient mice develop severe
      ketosis and hepatic steatosis, with evidence for inhibition of hepatic autophagy,
      a process that normally provides essential energy via degradation of hepatic
      triglycerides during starvation. We conclude that, during fasting, epinephrine is
      not required for glucose homeostasis, lipolysis or ketogenesis. Epinephrine may
      have an essential role in lipid handling, possibly via an autophagy-dependent
      mechanism.

PMID- 22405855
TI  - Comparison of ACR 1987 and ACR/EULAR 2010 criteria for predicting a 10-year
      diagnosis of rheumatoid arthritis.
AB  - OBJECTIVE: To compare the diagnostic accuracy of the 2010 American College of
      Rheumatology (ACR)/European League Against Rheumatism (EULAR) and 1987 ACR
      criteria for rheumatoid arthritis (RA) in a cohort of patients with recent-onset
      arthritis followed-up for 10 years. METHODS: One hundred and sixty-four patients
      with recent-onset arthritis of less than 1 year's duration were included
      prospectively between 1995 and 1997. The diagnosis of RA was defined as having a
      diagnosis of RA made by the office-based rheumatologist 10 years after enrolment.
      We compared the sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value (NPV) of the criteria sets at baseline. RESULTS: At
      baseline, 60 of the 164 patients had alternative diagnoses better explaining the
      arthritis and 13 had erosions typical for RA; of the 91 remaining patients, 33
      had at least 6 ACR/EULAR points (indicating definite RA), and 58 had fewer than 6
      points. The ACR/EULAR criteria had a quite similar sensitivity than the 1987 ACR
      criteria (33/57 [57.9%] for ACR/EULAR criteria vs 34/57 [59.6%] for the 1987 ACR
      criteria), but higher specificity, PPV, and NPV (95/107 [88.8%], 34/46 [73.9%],
      and 95/118 [80.5%], respectively) than the 1987 ACR criteria (80/107 [74.8%],
      33/63 [52.4%], and 80/104 [76.9%], respectively). CONCLUSION: ACR/EULAR criteria
      performed substantially better than ACR 1987 criteria for predicting a diagnosis
      of RA after 10 years. Much of the improvement was ascribable to the use of
      exclusion criteria. BULLET POINTS: (1) The ACR/EULAR criteria had the same
      sensitivity, but higher specificity, PPV, and NPV than the 1987 ACR criteria; (2)
      Much of the improvement was ascribable to the use of exclusion criteria.

PMID- 22405856
TI  - Bone health during late adolescence: effects of an 8-month training program on
      bone geometry in female athletes.
AB  - OBJECTIVES: This study investigated the short term changes in hip structural
      parameters in high level adolescent soccers and swimmers. METHODS: Twenty-six
      girl swimmers (15.9+/-2 years) and 32 girl soccer players (16.2+/-0.7 years) were
      investigated before and after 8 months of training. Fifteen non-active age
      matched adolescents were enrolled at baseline to serve as a reference group. The
      geometric contributions to bone strength in the proximal femur were quantified
      using the hip structural analysis technique. RESULTS: Eight months of training
      had increased the bone density in soccer players but not in swimmers. At the
      total hip, swimmers conserved their baseline low Z-score values while soccers
      remained above the normal. At the femoral shaft, the cross sectional area had
      increased for the two groups with a higher magnitude in soccers (3.17% vs 2.31%;
      P<0.05). The sub-periosteal width had increased in soccer players (P<0.01) but
      not in swimmers. The Z-score showed an improvement of cross sectional moment of
      inertia and section modulus at femoral shaft section for soccers (P<0.001),
      without any change in swimmers. Remarkably, swimmers had improved the Z-score of
      buckling ratio (P<0.005), while soccers did not. DISCUSSION/CONCLUSION: A season
      of training for sport characterized by impact had induced significant bone
      geometry improvement in late adolescent females despite expectations that this
      period of growth represents a plateau in bone maturation. This study adds to the
      existing literature describing intensive swimming practice as lacking an
      osteogenic effect when assessed by dual energy X-ray absorptiometry.

PMID- 22405857
TI  - Discitis and sacroiliitis diagnosed 15 years after iatrogenic Mycobacterium
      xenopi inoculation.
AB  - A patient was diagnosed with discitis and sacroiliitis due to Mycobacterium
      xenopi. He had a history of percutaneous nucleotomy performed 15 years earlier
      (in 1992) at the Clinique du Sport, Paris, France, during an outbreak of
      nosocomial M. xenopi infection at that institution. In 1997, magnetic resonance
      imaging performed as part of the routine follow-up program for patients who had
      surgery at the Clinique du Sport during the outbreak was not interpreted as
      indicating discitis; this assessment was confirmed by our review of the images.
      Bone and joint infections due to atypical mycobacteria are rare and can develop
      very slowly. To our knowledge, this is the first reported case of M. xenopi
      discitis with secondary extension to the sacroiliac joint in an immunocompetent
      patient.

PMID- 22405858
TI  - Genome regulation and evolution analysed by next-generation sequencing.

PMID- 22405859
TI  - Identification of novel HLA-A(*)0201-restricted CTL epitopes from Pokemon.
AB  - Pokemon is a member of the POK family of transcriptional repressors and aberrant
      overexpressed in various human cancers. Therefore, the related peptide epitopes
      derived from Pokemon is essential for the development of specific immunotherapy
      of malignant tumors. In this study, we predicted and identified HLA-A(*)0201
      restricted cytotoxic T lymphocyte (CTL) epitopes derived from Pokemon with
      computer-based epitope prediction, peptide-binding assay and testing of the
      induced CTLs toward different kinds of carcinoma cells. The results demonstrated
      that effectors induced by peptides of Pokemon containing residues 32-40, 61-69,
      87-95, and 319-327 could specifically secrete IFN-gamma and lyse tumor cell lines
      of Pokemon-positive and HLA-A2-matched. The results suggest that Pokemon32,
      Pokemon61, Pokemon87, and Pokemon319 peptides are novel HLA-A(*)0201-restricted
      restricted CTL epitopes, and could be utilized in the cancer immunotherapy
      against a broad spectrum of tumors.

PMID- 22405860
TI  - Leucine-rich glioma inactivated 3 regulates adipogenesis through ADAM23.
AB  - Leucine-rich glioma inactivated 3 (LGI3) is a secreted protein and a member of
      LGI/epitempin family. We previously showed that LGI3 was highly expressed in
      brain and played regulatory roles in neuronal exocytosis and differentiation.
      Besides the nervous system, LGI3 was shown to be expressed in diverse tissues. In
      this study, we found that LGI3 and its receptor candidate ADAM23 were expressed
      in adipose tissues and 3T3-L1 cells. 3T3-L1 preadipocytes secreted a 60-kDa
      protein, a major secreted form of LGI3, which declined with adipocyte
      differentiation. LGI3 was also expressed in adipose tissue macrophages in the
      ob/ob mice and in macrophage cell line. The 60-kDa LGI3 protein was selectively
      increased in the ob/ob adipose tissues comparing with the lean mice. Pull-down
      experiments, coimmunoprecipitation and immunocytochemistry indicated that LGI3
      associated with ADAM23 in adipose tissues and 3T3-L1 cells. Knockdown of LGI3 or
      ADAM23 by siRNA increased adipogenesis in 3T3-L1 cells. Treatment with LGI3
      protein did not affect preadipocyte proliferation but attenuated adipogenesis and
      this effect was reversed by siRNA-mediated knockdown of ADAM23. Taken together,
      we propose that LGI3 may be a candidate adipokine that is perturbed in obesity
      and suppresses adipogenesis through its receptor, ADAM23.

PMID- 22405861
TI  - Epileptic aura and qualitative alterations of consciousness in focal seizures: a
      neuropsychiatric approach.

PMID- 22405862
TI  - Effects of antiepileptic drug characteristics on medication adherence.
AB  - PURPOSE: To determine whether antiepileptic drug (AED) characteristics are
      associated with medication adherence. METHODS: We reviewed pharmacy and clinical
      records of 108 patients with epilepsy from the indigent care program at Shands
      Jacksonville. We calculated the mean medication possession ratio (MMPR) for each
      AED. Using univariate analysis, we determined whether differences exist in the
      MMPR of various AEDs. We also determined whether the MMPR differs accordingly to
      the use of mono- or combination therapy, dosing frequency, release-type, or brand
      name formulation. We employed multivariable analysis to determine if these
      differences persisted in the context of other demographic and clinical variables.
      RESULTS: Mean medication possession ratio was higher (better) when using older
      AEDs, in monotherapy, and with more frequent dosing intervals. These variables
      remained significant on multivariable analysis. CONCLUSION: Our findings
      contradict some commonly held beliefs on medication adherence and suggest that
      specific AED characteristics may be superseded by factors such as overall patient
      satisfaction with the drug regimen.

PMID- 22405863
TI  - Ictal aphasia: an unusual presentation of temporal lobe seizures.
AB  - Language disturbances during epileptic seizures are not uncommon, but isolated
      speech impairment is rare. We report a 67-year-old male with sudden onset of
      aphasia initially thought to be the result of an infarction of left middle
      cerebral artery territory. He had recurrent episodes of non-fluent, severely
      aphasic speech with intact comprehension as the primary manifestation, without
      other clinical seizure activity. After the administration of antiepileptic
      medication, his language returned to the baseline level. This case suggests that
      paroxysmal non-fluent aphasia can result from a seizure focus in the dominant
      temporal lobe. This is an important differential to be considered in patients
      with aphasia, which will assist in early diagnosis and treatment.

PMID- 22405864
TI  - Chronic administration of atorvastatin induced anti-convulsant effects in mice:
      the role of nitric oxide.
AB  - Atorvastatin has neuroprotective effects, and there is some evidence that nitric
      oxide is involved in atorvastatin effects. In this study, we evaluated whether
      the nitrergic system is involved in the anticonvulsant effects of chronic
      atorvastatin administration. Intravenous and intraperitoneal pentylenetetrazol
      were used to induce seizures in mice. Chronic atorvastatin treatment
      significantly increased the seizure threshold which is induced by both
      intravenous and intraperitoneal pentylenetetrazol. Intraperitoneal
      pentylenetetrazol also decreased the incidence of tonic seizure and death in
      atorvastatin-treated groups. Chronic co-administration of a non-selective nitric
      oxide synthase inhibitor, l-NAME, or a selective inducible nitric oxide synthase
      inhibitor, aminoguanidine, with atorvastatin inhibited atorvastatin-induced
      anticonvulsant effects in intravenous model of pentylenetetrazol. Acute injection
      of l-NAME or aminoguanidine inhibited the anticonvulsant effects of atorvastatin
      in both models of intravenous- and intraperitoneal-pentylenetetrazol-induced
      seizures. In conclusion, we demonstrated that nitric oxide signaling probably
      through inducible nitric oxide synthase could be involved in the anticonvulsant
      effects of atorvastatin.

PMID- 22405866
TI  - Checkpoint-independent stabilization of kinetochore-microtubule attachments by
      Mad2 in human cells.
AB  - Faithful chromosome segregation is required for cell and organism viability and
      relies on both the mitotic checkpoint and the machinery that corrects kinetochore
      microtubule (k-MT) attachment errors. Most solid tumors have aneuploid karyotypes
      and many missegregate chromosomes at high rates in a phenomenon called
      chromosomal instability (CIN). Mad2 is essential for mitotic checkpoint function
      and is frequently overexpressed in human tumors that are CIN. For unknown
      reasons, cells overexpressing Mad2 display high rates of lagging chromosomes.
      Here, we explore this phenomenon and show that k-MT attachments are
      hyperstabilized by Mad2 overexpression and that this undermines the efficiency of
      correction of k-MT attachment errors. Mad2 affects k-MT attachment stability
      independently of the mitotic checkpoint because k-MT attachments are unaltered
      upon Mad1 depletion and Mad2 overexpression hyperstabilizes k-MT attachments in
      Mad1-deficient cells. Mad2 mediates these effects with Cdc20 by altering the
      centromeric localization and activity of Aurora B kinase, a known regulator of k
      MT attachment stability. These data reveal a new function for Mad2 to stabilize k
      MT attachments independent of the checkpoint and explain why Mad2 overexpression
      increases chromosome missegregation to cause chromosomal instability in human
      tumors.

PMID- 22405867
TI  - Short-term memory of motor network performance via activity-dependent
      potentiation of Na+/K+ pump function.
AB  - Brain networks memorize previous performance to adjust their output in light of
      past experience. These activity-dependent modifications generally result from
      changes in synaptic strengths or ionic conductances, and ion pumps have only
      rarely been demonstrated to play a dynamic role. Locomotor behavior is produced
      by central pattern generator (CPG) networks and modified by sensory and
      descending signals to allow for changes in movement frequency, intensity, and
      duration, but whether or how the CPG networks recall recent activity is largely
      unknown. In Xenopus frog tadpoles, swim bout duration correlates linearly with
      interswim interval, suggesting that the locomotor network retains a short-term
      memory of previous output. We discovered an ultraslow, minute-long
      afterhyperpolarization (usAHP) in network neurons following locomotor episodes.
      The usAHP is mediated by an activity- and sodium spike-dependent enhancement of
      electrogenic Na(+)/K(+) pump function. By integrating spike frequency over time
      and linking the membrane potential of spinal neurons to network performance, the
      usAHP plays a dynamic role in short-term motor memory. Because Na(+)/K(+) pumps
      are ubiquitously expressed in neurons of all animals and because sodium spikes
      inevitably accompany network activity, the usAHP may represent a phylogenetically
      conserved but largely overlooked mechanism for short-term memory of neural
      network function.

PMID- 22405868
TI  - Path integration controls nest-plume following in desert ants.
AB  - The desert ant Cataglyphis fortis is equipped with sophisticated navigational
      skills for returning to its nest after foraging. The ant's primary means for long
      distance navigation is path integration, which provides a continuous readout of
      the ant's approximate distance and direction from the nest. The nest is
      pinpointed with the aid of visual and olfactory landmarks. Similar landmark cues
      help ants locate familiar food sites. Ants on their outward trip will position
      themselves so that they can move upwind using odor cues to find food. Here we
      show that homing ants also move upwind along nest-derived odor plumes to approach
      their nest. The ants only respond to odor plumes if the state of their path
      integrator tells them that they are near the nest. This influence of path
      integration is important because we could experimentally provoke ants to follow
      odor plumes from a foreign, conspecific nest and enter that nest. We identified
      CO(2) as one nest-plume component that can by itself induce plume following in
      homing ants. Taken together, the results suggest that path-integration
      information enables ants to avoid entering the wrong nest, where they would
      inevitably be killed by resident ants.

PMID- 22405865
TI  - Reconstructing community assembly in time and space reveals enemy escape in a
      Western Palearctic insect community.
AB  - How geographically widespread biological communities assemble remains a major
      question in ecology. Do parallel population histories allow sustained
      interactions (such as host-parasite or plant-pollinator) among species, or do
      discordant histories necessarily interrupt them? Though few empirical data exist,
      these issues are central to our understanding of multispecies evolutionary
      dynamics. Here we use hierarchical approximate Bayesian analysis of DNA sequence
      data for 12 herbivores and 19 parasitoids to reconstruct the assembly of an
      insect community spanning the Western Palearctic and assess the support for
      alternative host tracking and ecological sorting hypotheses. We show that
      assembly occurred primarily by delayed host tracking from a shared eastern
      origin. Herbivores escaped their enemies for millennia before parasitoid pursuit
      restored initial associations, with generalist parasitoids no better able to
      track their hosts than specialists. In contrast, ecological sorting played only a
      minor role. Substantial turnover in host-parasitoid associations means that
      coevolution must have been diffuse, probably contributing to the parasitoid
      generalism seen in this and similar systems. Reintegration of parasitoids after
      host escape shows these communities to have been unsaturated throughout their
      history, arguing against major roles for parasitoid niche evolution or
      competition during community assembly.

PMID- 22405869
TI  - The impact of visible light on the immature retina: a model of early light
      exposure in neonatal mice.
AB  - To investigate the effects of visible light on the retinal development, we
      established an early-light-exposure model in neonatal mice. An incision was made
      on the right-sided eyelids of mice on postnatal day 4 (P4), and so that the right
      eyes were exposed to visible light (4000 lux) for 12h per day. The population in
      the retinal ganglion cells (RGCs), cellular apoptosis and lumican expression were
      analyzed in the retinae. The loss of the RGCs was moderately alleviated and
      dramatically increased by early light exposure on P9 and P12, respectively. In
      the light-exposed retinae, the immunoactivities of caspase-9 (p39), an active
      isoform of caspase-9 marking the cellular apoptosis, dropped to nearly 30% of
      those in the control specimens on P6; thereafter the light-induced lower levels
      of caspase-9 (p39) remained, while those in the control specimens dropped to the
      values less than 50% of the light-exposed retinae. Lumican was first ectopically
      detected on P9, and distributed in the inner layers of the light-exposed retinae,
      with the most significant accumulation in the ganglion cell layer by P12. The
      ectopic expression of lumican was both temporarily and spatially parallel with
      the aggravated loss of the RGCs. In conclusion, early light exposure inflicts a
      profound effect on the immature retina. Our studies may have implications for
      premature infant care.

PMID- 22405870
TI  - Associations between microRNA (miR-21, 126, 155 and 221), albuminuria and heavy
      metals in Hong Kong Chinese adolescents.
AB  - BACKGROUND AND AIM: Pathogenetic mechanisms underlying albuminuria are not
      completely understood. Heavy metals might lead to atherosclerosis and kidney
      damage. miR-21, 126, 155 and 221 regulated endothelial function and might
      contribute to the development of albuminuria. To date, no clinical trial has
      explored the relationship between miRNAs, microalbuminuria and heavy metals in
      human. In this study, we aimed to examine the association between
      microalbuminuria, miRNAs and heavy metals in adolescents. MATERIALS AND METHODS:
      From a cross-sectional, population-recruited study, we identified 60 school
      children aged 12-19 years with microalbuminuria (defined as spot urine albumin
      creatinine ratio >3.5 mg/mmol). We compared the urine heavy metals (arsenic,
      mercury, cadmium and lead) and miRNAs levels (miR-21,126, 155 and 221) with
      another 60 age-and sex-matched normoalbuminuric adolescents as control. RESULTS:
      Mean age of the study cohort was 15.5+/-2.1 years. 43% were boys. Among the four
      miRNAs tested, only miR-21 was associated with microalbuminuria (p=0.02). Urinary
      arsenic and lead levels had a negative association with both miR-21 and miR-221.
      No significant association was found between heavy metals examined and
      microalbuminuria. CONCLUSION: The results of our study suggest an association
      between microalbuminuria, miR-21 and heavy metals (arsenic and lead). This might
      imply that miR-21 is involved in the pathogenetic mechanisms linking heavy metals
      exposure and albuminuria.

PMID- 22405871
TI  - Three liver grafts from a deceased whole liver.
AB  - Although the lateral segment (LS) from the split-liver of a deceased donor or a
      live donor can increase the organ pool of pediatric patients awaiting liver
      transplantation, the shortage of organ donation in Asia countries is still
      serious and results in high death rates of pediatric patients. The medial segment
      (MS) of the liver is sacrificed during the standard technique of splitting a
      whole liver into an LS and an extended right liver because the cutting sites of
      portal vein, hepatic artery and bile duct are all in the bifurcation of the liver
      hilum to have adequate length of vascular and biliary pedicles for easier
      grafting. However, the surgical techniques of vascular and biliary
      reconstructions for liver transplantation, particularly from the experiences of
      living donor liver transplantation, have been much improved in the last decade.
      Therefore it may be possible for an additional MS of the liver to be an isolated
      graft for a small recipient on the premise that grafts of right lobe (RL) and LS
      are minimally injured. In light of detailed reviews of anatomies of hepatic
      arteries, hepatic veins, portal veins and bile ducts, the dissection and
      reconstruction of vessels and bile ducts for the MS can possibly be performed if
      the extra-hepatic length of the artery to the MS is long enough. As the artery
      for the MS, middle hepatic artery (MHA), usually derives from a branch of the
      left hepatic artery and often in the liver parenchyma, the length is usually too
      short to be reconstructed. If the MHA for the MS is isolated and its extra
      hepatic length is more than 1cm, triple liver grafts from a deceased whole liver,
      consisting of the RL, MS and LS may be possible. The anatomies of the hepatic
      artery in abdominal computed tomography (CT) or magnetic resonance imaging (MRI)
      for live liver donors in our institution were retrospectively analyzed. The
      results showed that three types of hepatic arterial anatomies could be considered
      for possible recovery of triple segments: type I is an accessory left gastric
      artery to feed the lateral segment; type II is an isolated MHA; type III is an
      early bifurcation of the left hepatic artery and MHA.

PMID- 22405872
TI  - A call for evidence: timing of surgery in burns.

PMID- 22405873
TI  - Differential expression of genes associated with lipid metabolism in longissimus
      dorsi of Korean bulls and steers.
AB  - The objective of this study was to compare expression of genes associated with
      lipid deposition and removal between bulls and steers in the longissimus dorsi
      muscle (LM) tissue of Korean cattle. Castration increased the expression of lipid
      uptake lipoprotein lipase, fatty acid translocase, and fatty acid transport
      protein 1 in LM. Castration increased lipogenic gene expression of both acetyl
      CoA carboxylase and fatty acid synthase. In contrast, castration downregulated
      lipolytic gene expression of both adipose triglyceride lipase (ATGL) and
      monoglyceride lipase. Steers showed higher expression levels of insulin signaling
      phospho-v-akt murine thymoma viral oncogene homolog 1 than bulls but lower
      protein levels of nuclear Forkhead box O 1 (FoxO1) than bulls, suggesting that
      increased insulin signaling following castration decreases nuclear FoxO1 levels,
      leading to downregulation of ATGL gene expression. These findings suggest that
      castration contributes to increases in lipid uptake and lipogenesis and a
      decrease in lipolysis, resulting in improved marbling.

PMID- 22405874
TI  - Genetic analysis on growth and carcass traits in Nelore cattle.
AB  - In this study, the objective was to estimate genetic parameters of body weight at
      210 (BW210) and 365 (BW365) days of age in relation to rib eye area (REA),
      subcutaneous back fat thickness (BF) and rump fat (RF), and their respective
      genetic trends, in Nelore beef cattle. Estimates of genetic parameters and
      breeding values for the studied traits were obtained using the REML method. The
      direct and maternal heritability estimates were respectively: 0.25+/-0.02 and
      0.21+/-0.01, for BW210, and 0.29+/-0.02 and 0.09+/-0.01, for BW365. The
      heritability estimates for transformed REA, BF and RF were 0.29+/-0.03, 0.21+/
      0.02 and 0.23+/-0.03, respectively. There were genetic associations between BW210
      and REA, BW365 and REA, and BF and RF, while the other correlations were low. The
      selection process that was conducted at the farms participating in the breeding
      program, taking the proposed selection index into consideration, caused genetic
      changes to these traits.

PMID- 22405875
TI  - Meat quality comparison between fresh and frozen/thawed ostrich M. iliofibularis.
AB  - A pairwise comparison of the meat quality between fresh and frozen/thawed
      Musculus iliofibularis was conducted. Thirty-two (16 left; 16 right) muscles were
      collected and allocated to two treatments: fresh and frozen/thawed. Frozen vacuum
      packed samples were stored for 1 month at -20 degrees C before thawing. The fresh
      samples had higher pH (P<0.05), water binding capacity (P<0.05), CIE L*
      (P<0.0001), CIE a* (P<0.05) and Chroma values (P<0.05) than the frozen/thawed
      samples, indicating the fresh samples were bright red in appearance and had
      minimal exudate. The frozen/thawed samples lost 5.09+/-0.21% moisture during
      thawing and had a greater drip loss (P<0.0001) and shear force (P<0.001). No
      differences were obtained with regard to cooking loss, CIE b*, hue and TBARS.
      Protein oxidation (mM carbonyls/mg protein) was lower (P<0.05) in the
      frozen/thawed samples, which was attributed to the higher (P<0.0001) protein
      concentration negating the higher (P<0.001) carbonyl content. Industrial freezing
      and thawing regimes negatively affected the quality of ostrich meat.

PMID- 22405876
TI  - A false single nucleotide polymorphism generated by gene duplication compromises
      meat traceability.
AB  - Controlling meat traceability using SNPs is an effective method of ensuring food
      safety. We have analyzed several SNPs to create a panel for bovine genetic
      identification and traceability studies. One of these was the transversion
      g.329C>T (Genbank accession no. AJ496781) on the cytochrome P450 17A1 gene, which
      has been included in previously published panels. Using minisequencing reactions,
      we have tested 701 samples belonging to eight Spanish cattle breeds.
      Surprisingly, an excess of heterozygotes was detected, implying an extreme
      departure from Hardy-Weinberg equilibrium (P<0.001). By alignment analysis and
      sequencing, we detected that the g.329C>T SNP is a false positive polymorphism,
      which allows us to explain the inflated heterozygotic value. We recommend that
      this ambiguous SNP, as well as other polymorphisms located in this region, should
      not be used in identification, traceability or disease association studies.
      Annotation of these false SNPs should improve association studies and avoid
      misinterpretations.

PMID- 22405877
TI  - The photophysics of a Rhodamine head labeled phospholipid in the identification
      and characterization of membrane lipid phases.
AB  - The organization of lipids and proteins into domains in cell membranes is
      currently an established subject within biomembrane research. Fluorescent probes
      have been used to detect and characterize these membrane lateral heterogeneities.
      However, a comprehensive understanding of the link between the probes'
      fluorescence features and membrane lateral organization can only be achieved if
      their photophysical properties are thoroughly defined. In this work, a systematic
      characterization of N-(lyssamine Rhodamine B sulfonyl)-1,2-dioleoyl-sn-3
      phosphatidylehanolamine (Rhod-DOPE) absorption and fluorescence behavior in gel,
      liquid-ordered (l(o)) and liquid-disordered (l(d)) model membranes was performed.
      In agreement with a previous study, it was found that Rhod-DOPE fluorescence
      lifetimes present a strong sensitivity to lipid phases, becoming significantly
      shorter in l(o) membranes as the probe membrane concentration increases. The
      sensitivity of Rhod-DOPE absorption and fluorescence properties to the membrane
      phase was further explored. In particular, the fluorescence lifetime sensitivity
      was shown to be a consequence of the enhanced Rhod-DOPE fluorescence dynamic self
      quenching, due to the formation of probe-rich membrane domains in these condensed
      phases that cannot be considered as typical probe aggregates, as excitonic
      interaction is not observed. The highly efficient dynamic self-quenching was
      shown to be specific to l(o) phases, pointing to an important effect of membrane
      dipole potential in this process. Altogether, this work establishes how to use
      Rhod-DOPE fluorescence properties in the study of membrane lipid lateral
      heterogeneities, in particular cholesterol-enriched lipid rafts.

PMID- 22405878
TI  - Quantifying the differential effects of DHA and DPA on the early events in visual
      signal transduction.
AB  - A range of evidence from animal, clinical and epidemiological studies indicates
      that highly polyunsaturated acyl chains play important roles in development,
      cognition, vision and other aspects of neurological function. In a number of
      these studies n3 polyunsaturated fatty acids (PUFAs) appear to be more
      efficacious than n6 PUFAs. In a previous study of retinal rod outer segments
      obtained from rats raised on either an n3 adequate or deficient diet, we
      demonstrated that the replacement of 22:6n3 by 22:5n6 in the n3 deficient rats
      led to functional deficits in each step in the visual signaling process (Niu et
      al., 2004). In this study, we examined rhodopsin and phosphodiesterase function
      and acyl chain packing properties in membranes consisting of phosphatidylcholines
      with sn-1=18:0, and sn-2=22:6n3, 22:5n6, or 22:5n3 in order to determine if
      differences in function are due to the loss of one double bond or due to
      differences in double bond location. At 37  degrees C the n6 lipid shifted the
      equilibrium between the active metarhodopsin II (MII) state and inactive
      metarhodopsin I (MI) state towards MI. In addition, 22:5n6 reduced the rates of
      MII formation and MII-transducin complex formation by 2- and 6-fold,
      respectively. At a physiologically relevant level of rhodopsin light stimulation,
      the activity of phosphodiesterase was reduced by 50% in the 22:5n6 membrane,
      relative to either of the n3 membranes. Activity levels in the two n3 membranes
      were essentially identical. Ensemble acyl chain order was assessed with time
      resolved fluorescence measurements of the membrane probe diphenylhexatriene
      (DPH). Analysis in terms of the orientational distribution of DPH showed that
      acyl chain packing in the two n3 membranes is quite similar, while in the 22:5n6
      membrane there was considerably less packing disorder in the bilayer midplane.
      These results demonstrate that the n3 bond configuration uniquely optimizes the
      early steps in signaling via a mechanism which may involve acyl chain packing
      deep in the bilayer.

PMID- 22405879
TI  - Development of an in vitro system to measure the sensitivity to the antiviral Mx
      protein of fish viruses.
AB  - Mx is a structural protein, induced by type I interferon (IFN), with direct
      antiviral properties. In fish the inherent contribution of Mx protein to viral
      protection is unknown. The transgenic Chinook salmon embryonic (CHSE)-TOF cell
      line was genetically modified to express the rainbow trout Mx (rbtMx1) protein
      under the control of the tetracycline derivative, doxycycline (DOX). Two clones
      CHSE-TOF-MX8 and CHSE-TOF-MX10 were isolated and characterised by qPCR. The level
      of resistance to Infectious Pancreatic Necrosis Virus (IPNV), Salmon Alphavirus
      (SAV), Infectious Haematopoietic Necrosis Virus (IHNV) and Epizootic
      Haematopoietic Necrosis Virus (EHNV) of the CHSE-TOF, CHSE-TOF-MX8 and CHSE-TOF
      MX10 cell lines cultivated with and without DOX was measured. A novel method was
      established to measure accurately the level of sensitivity of any given viral
      isolate to Mx protein. IPNV and SAV viruses were highly sensitive to the presence
      of rbtMx1 in the cells whereas IHNV and EHNV showed partial resistance suggesting
      contrasting viral evasion strategies between these categories of viruses.

PMID- 22405880
TI  - Confirmation of a new conserved linear epitope of Lyssavirus nucleoprotein.
AB  - Bioinformatics analysis was used to predict potential epitopes of Lyssavirus
      nucleoprotein and highlighted some distinct differences in the quantity and
      localization of the epitopes disclosed by epitope analysis of monoclonal
      antibodies against Lyssavirus nucleoprotein. Bioinformatics analysis showed that
      the domain containing residues 152-164 of Lyssavirus nucleoprotein was a
      conserved linear epitope that had not been reported previously. Immunization of
      two rabbits with the corresponding synthetic peptide conjugated to the Keyhole
      Limpe hemocyanin (KLH) macromolecule resulted in a titer of anti-peptide antibody
      above 1:200,000 in rabbit sera as detected by indirect enzyme-linked
      immunosorbent assay (ELISA). Western blot analysis demonstrated that the anti
      peptide antibody recognized denatured Lyssavirus nucleoprotein in sodium
      dodecylsulfonate-polyacrylate gel electrophoresis (SDS-PAGE). Affinity
      chromatography purification and FITC-labeling of the anti-peptide antibody in
      rabbit sera was performed. FITC-labeled anti-peptide antibody could recognize
      Lyssavirus nucleoprotein in BSR cells and canine brain tissues even at a 1:200
      dilution. Residues 152-164 of Lyssavirus nucleoprotein were verified as a
      conserved linear epitope in Lyssavirus.

PMID- 22405881
TI  - Toxicological implications of the delivery of fentanyl from gel extracted from a
      commercial transdermal reservoir patch.
AB  - Fentanyl in a rate controlling membrane (RCM) transdermal patch form has been
      available since the early 1990s for outpatient management of chronic pain.
      Fatalities associated with misuse or overuse of fentanyl patches have been
      reported. Concerns have also been raised about the possibility that defects in
      such patches may result in leaking of the reservoir of the patch onto patients'
      skin and consequent overdose. In order to investigate the possibility of fentanyl
      toxicity arising from leaking of patches, the permeation of fentanyl from the
      reservoir gel of a commercially available fentanyl transdermal patch was examined
      in vitro. Finite doses of the formulation were applied to human skin and
      permeation was monitored, at 32 degrees C under non-occluded conditions, for 48
      h. Similar levels of skin permeation of fentanyl from the 1% gel formulation were
      obtained for the two skin donor samples tested. After 48 h, the dose of fentanyl
      that had permeated was 7.4 (+/- 3.6)% and 7.7 (+/- 1.9)% of the respective total
      amounts applied. At the end of the experiment, most of the drug was found in the
      residual formulation at the skin surface (i.e. 63-66%). For both the skin
      samples, a relatively small amount of the fentanyl applied (2-3%) was present in
      the skin at 48 h after application. The maximum flux from the data generated was
      between 6 and 24h over which time frame it was 0.3 MUg/cm(2)/h. Assuming
      spreading of leaked gel over an area of 100 cm(2), this would result in a plasma
      level of 0.6 ng/mL. The anticipated plasma levels from a 100 MUg/h patch are
      known to be approximately 2.5 ng/ml. Thus, the maximum increase in the plasma
      levels from a patch which leaks gel is calculated to be, at most, about 25%.

PMID- 22405882
TI  - Formation of excess sublobules in the cerebellum of hypothyroid rats.
AB  - Cerebellar folia may increase in number in hypothyroid rats (Lauder et al., 1974;
      Hasebe et al., 2008a). In this study, we aimed to confirm the formation of an
      excess sublobule and to determine whether excess sublobules are consistently
      formed in conserved positions in hypothyroid rats. Instead of the foliation
      pattern partitioned by cerebellar fissures, we employed the bifurcation pattern
      of the internal granular layer for investigation of complexity of the cerebellar
      cortex in hypothyroid rats. The basic foliation pattern of the cerebellum was
      intact in hypothyroid rats, but lobules III to IX frequently showed an increase
      in the number of sublobules. The excess sublobules were mainly found in the folia
      and along the shallow region of the fissure. In other words, the excess
      sublobules were not located in random locations but rather in specific locations.
      The area in the internal granular layer of lobules V to IX was significantly
      larger than that in control rats. From the increased area of the internal
      granular layer it may be inferred that internal granular cells increase in number
      than those in normal rats. In our study, regions within the cerebellum that show
      an excess of sublobules correlate with regions that show an intermediate to late
      forming internal granular layer (Altman, 1969). Our observations fit with the
      view that excess sublobules are formed by the external granular layer showing
      prolonged cell proliferation and hypothyroidism predominantly has an adverse
      impact on the intermediate to late phases in development of the internal granular
      layer.

PMID- 22405883
TI  - Head and neck cancer with lower neck nodal metastases: management of 23 cases and
      review of the literature.
AB  - To investigate the patient outcomes associated with the applied modes of therapy
      in head and neck cancer with lower neck nodal metastases. The medical records of
      23 consecutive individuals who were managed by intent to treat for head and neck
      cancer with metastatic disease in the lower neck nodes over a 19-year period were
      reviewed. The mean age was 53.5 years, and the larynx was the most frequently
      affected primary site (57%). Overall, locoregional tumor control was achieved in
      the majority (75%) of the cases and the 2-year survival rate was 48%. The 2-year
      survival rates of people managed by surgery and postoperative radiotherapy,
      chemoradiation or single modality therapy were 63%, 56% and 17%, respectively,
      (p=0.04). Aggressive therapy resulted in five (22%) long-term (>5 years)
      survivors. The combination of treatment modalities proved to be effective
      management for head and neck cancer with lower neck nodal metastases and should
      be further investigated in prospective trials.

PMID- 22405885
TI  - Mixed methods research--so far easier said than done?
AB  - Mixed methods research (MMR) involves the application of both quantitative and
      qualitative approaches in a single study, and has been advocated for
      physiotherapy research. MMR studies are considered to be useful in cases where
      several different but related research questions are examined or when the purpose
      is to triangulate quantitative and qualitative data addressing one research
      question. Few MMR studies have been published in physiotherapy journals, and no
      papers are found to discuss the actual experience of conducting an MMR study. In
      this paper an MMR study is used to exemplify how a study applying a concurrent
      triangulation design was performed, and some aspects related to performing MMR
      are discussed. Some challenges are identified, and questions are raised about how
      to incorporate the findings of the two data sets and which skills are needed for
      doing MMR.

PMID- 22405884
TI  - Assessment of methadone clinic staff attitudes toward hepatitis C evaluation and
      treatment.
AB  - We used a 25-item, self-administered questionnaire to assess staff's perceived
      barriers and willingness to engage in onsite treatment of hepatitis C virus (HCV)
      at the Beth Israel Medical Center methadone maintenance treatment program (MMTP)
      at its Harlem sites. Of 80 participants, 50% were counselors and 24% were
      directly involved in referral or HCV testing. Although 92% of the MMTP staff
      indicated that they discuss HCV evaluation and treatment with patients at least
      annually, 70% believed that less than 25% of patients accept referral for HCV
      treatment and attend their initial appointment. Most staff (66%) supported onsite
      HCV evaluation and treatment, although support was higher among those with a
      bachelor's degree or higher (p = 0.046). Lack of infrastructure was perceived as
      the greatest obstacle to onsite treatment. Educational interventions and skill
      building for staff to confidently engage and support MMTP patients in HCV
      treatment may be necessary prerequisites for onsite HCV management in MMTPs.

PMID- 22405886
TI  - [Post-surgical complications and mortality after two-stage coloanal anastomosis
      using the Turnbull-Cutait procedure].
AB  - INTRODUCTION: As colo-anal anastomoses continue to have a high risk of post
      surgical dehiscence it is recommended to combine this with a protective stoma.
      The main purpose of this study was to determine the post-operative morbidity and
      mortality rate in patients operated on using the Turnbull-Cutait (T-C) technique
      with delayed colo-anal anastomosis without a protective ileostomy. MATERIAL AND
      METHODS: An observational study was conducted on 17 patients. The surgical
      indication was classified as "primary" (group I), and "secondary" (group II) when
      rescue was performed due to complications in the short to long-term after rectal
      resection. The surgical technique consisted of two stages: 1) low anterior
      resection, circumferential mucosectomy from the pectinate line, pulling the colon
      through the anal canal; 2) resection of the pull-through segment and colo-anal
      anastomosis between the fifth and tenth day. Demographic data, associated
      comorbidities, and ASA score were recorded, as well as post-surgical
      complications, post-surgical mortality, and technical failure (defined as
      performing a definitive stoma). RESULTS: The review consisted of 13 patients in
      group I and 4 in group II. Twelve patients were operated on due to rectal cancer,
      one patient due to a recto-vesico-vaginal fistula, two due to rescue of early
      complications (from the Emergency Department), and two were operated due to
      chronic complications after rectal resection. Six patients (35.3%) had one or
      more complications, three of them required new surgery. There were no
      postoperative deaths. CONCLUSIONS: The T-C could be a first option in cancer of
      the rectum, with no need for a protective ileostomy. It could be an alternative
      in urgent re-interventions of patients who have rectal surgery complications.

PMID- 22405887
TI  - [Presacral haemorrhage during rectal cancer resection: morphological and
      hydrodynamic considerations].
AB  - INTRODUCTION: Our aim is to identify the location and size of the anterior
      foramina of sacral vertebral bodies and analyse the haemodynamic variables that
      could influence the haemorrhagic severity of the injury of the presacral venous
      plexus. MATERIALS AND METHODS: Using computed axial tomography the morphological
      data of 70 sacral bones in 67 patients with rectal cancer were recorded, as well
      as measuring the height between the vena cava and S5. After transfemoral
      catheterisation the inferior vena cava pressure was recorded in 10 patients with
      rectal cancer. Hydrodynamic principles, according to Bernoulli's Law, were
      applied to calculate sacral venous plexus pressure, and the flow rate according
      to the calibre of a hypothetical venous injury. RESULTS: The maximum diameter
      ranged from 0.5mm to 4mm in 22% of the cases. All foramina of 2 or more
      millimetres were located in the S4-S5 region. Sacral plexus venous pressure in
      lithotomy was almost double the inferior vena cava pressure in normal position.
      Blood flow ranged from 498 to 1,994 ml/min for injuries of sizes between 2 and
      4mm, respectively. CONCLUSIONS: Larger calibre foramina are found in vertebral
      bodies of S4-S5. Venous injury at these levels can reach a flow rate of 2 l/min.

PMID- 22405888
TI  - Cell therapy: promise fulfilled?
AB  - Cellular immunotherapy has been widely accepted as a new powerful modality of
      cancer treatment. The last 2 decades have seen impressive results in its
      application against haemato-oncologic malignancies, melanomas and prostate
      carcinoma. Cellular immunotherapy has since found applicability beyond cancer
      into autoimmunity and continues to expand in its clinical applicability. The
      discovery that stem cells have the ability to differentiate into more mature cell
      types, like neurones and myocardium, has focused research on using exogenous
      cells to repair damaged tissues. This led to numerous clinical trials using stem
      cells in myocardial infarction, cardiomyopathy and spinal cord damage. Results
      have ranged from modest to significant clinical outcomes with continuing debate
      on the exact process of regeneration achieved. The intertwining between cell
      therapy and transfusion medicine now includes research on progenitor cells for
      the production of mature red cells. It is also clear that cell therapy has
      enabled an improved understanding of the pathogenesis and clinical course of many
      diseases, while perhaps its role in regenerative medicine is most enticing.
      However, the critical role of manufacturing in terms of cost, complexity,
      reproducibility, and regulatory matters remains a central issue in the
      consideration of whether cell therapy has met all of its promise.

PMID- 22405890
TI  - Metallothionein-II improves motor function recovery and increases spared tissue
      after spinal cord injury in rats.
AB  - After spinal cord injury (SCI), a complex cascade of pathophysiological processes
      rapidly damages the nervous tissue. The initial damage spreads to the surrounding
      tissue by different mechanisms, including oxidative stress. We have recently
      reported that the induction of metallothionein (MT) protein is an endogenous
      rapid-response mechanism after SCI. Since the participation of MT in
      neuroprotective processes after SCI is still unknown, the aim of the present
      study was to evaluate the possible neuroprotective effect of exogenously
      administered MT-II during the acute phase after SCI in rats. Female Wistar rats
      weighing 200-250g were submitted to spinal cord contusion by means of a computer
      controlled device (NYU impactor). Rats received several doses of MT-II (3.2, 10
      and 100MUg) at 2 and 8h after SCI. Results of the BBB scale were statistically
      analysed using an ANOVA of repeated-measures, followed by Tukey's test. Among the
      three doses tested, only 10 and 100MUg were able to significantly increase
      (p<0.05) BBB scale scores eight weeks after SCI from a mean of 7.88 in the
      control group, to means of 12.63 and 10.88 for the 10 and 100MUg doses of MT-II,
      respectively. The amount of spared tissue was also higher in the groups treated
      with 10 and 100MUg, as compared to the control group values. Results from the
      present study demonstrate a significant neuroprotective effect of exogenously
      administered MT-II. Further studies are needed in order to characterize the
      mechanisms involved in this neuroprotective action.

PMID- 22405891
TI  - Recellularized nerve allografts with differentiated mesenchymal stem cells
      promote peripheral nerve regeneration.
AB  - Chemical-extracted acellular nerve allografting, containing the natural nerve
      structure and elementary nerve extracellular matrix (ECM), has been used for
      peripheral nerve-defect treatment experimentally and clinically. However,
      functional outcome with acellular nerve allografting decreases with increased
      size of gap in nerve defects. Cell-based therapy is a good strategy for repairing
      long nerve defects. Bone-marrow-derived mesenchymal stem cells (BMSCs) and
      adipose-derived mesenchymal stem cells (ADSCs) can be induced to differentiate
      into cells with Schwann cell-like properties (BMSC-SCs or ADSC-SCs), which have
      myelin-forming ability in vitro and secrete trophic nerve growth factors. Here,
      we aimed to determine whether BMSC-SCs or ADSC-SCs are a promising cell type for
      enriching acellular grafts in nerve repair. We evaluated axonal regeneration
      distance by immunofluorescence staining after 2-week implantation. We used
      functional and histomorphometric analysis to evaluate 3-month regeneration of the
      novel cell-supplemented tissue-engineered nerve graft used to bridge a 15-mm-long
      sciatic nerve gap in rats. Introducing BMSC-SCs or ADSC-SCs to the acellular
      nerve graft promoted sciatic nerve regeneration and functional recovery. Nerve
      regeneration with BMSC-SCs or ADSC-SCs was comparable to that with autografting
      and Schwann cells alone and better than that with acellular nerve allografting
      alone. Differentiated bone-marrow-or adipose-derived MSCs may be a promising cell
      source for tissue-engineered nerve grafts and promote functional recovery after
      peripheral nerve injury.

PMID- 22405892
TI  - Testosterone up-regulates seladin-1 expression by iAR and PI3-K/Akt signaling
      pathway in C6 cells.
AB  - The previous study indicated that DHCR24/seladin-1 was an important
      neuroprotective effector. However, the molecular mechanisms that androgen
      modulates the expression of seladin-1 remain incompletely defined. In this paper,
      we showed that the expression of seladin-1 was significantly increased by
      testosterone at all concentrations tested at the protein and mRNA levels in C6
      cells, the selective AR antagonist flutamide obviously inhibited the effect in a
      concentration-dependent manner. Furthermore, we found that testosterone
      significantly increased the phosphorylation level of V-akt murine thymoma viral
      oncogene (Akt), a key effector of the phosphoinositide 3-kinase (PI3-K)/Akt
      signaling pathway, while a specific PI3-K inhibitor LY294002 obviously prevented
      the activation of Akt phosphorylation. In addition, the PI3-K inhibitor LY294002
      also markedly blocked the up-regulation expression of seladin-1 gene induced by
      testosterone at the protein and mRNA levels. Collectively, the above results
      suggested that testosterone regulated the expression of seladin-1 by the
      intracellular androgen receptor (iAR)-mediated genomic signaling pathway and the
      non-genomic PI3-K/Akt signaling pathway in C6 glial cells.

PMID- 22405893
TI  - Association of angiotensin-converting enzyme functional gene I/D polymorphism
      with amnestic mild cognitive impairment.
AB  - The relationship between angiotensin-converting enzyme (ACE) gene
      insertion/deletion (I/D) polymorphism and serum ACE activity, as well as amnestic
      mild cognitive impairment (aMCI), was investigated. The study recruited 90 aMCI
      patients and 90 matched healthy controls. All subjects underwent an extensive
      assessment of cognitive function. The ACE gene I/D genotype was determined by
      polymerase chain reaction. Serum ACE activity was measured using a
      spectrophotometric technique. The scores obtained by the aMCI patients on the
      neuropsychological tests were significantly lower than those of the control
      subjects (all p<0.01). The genotype (chi(2)=11.510) and allele (chi(2)=6.945)
      frequencies of the ACE gene were significantly different between the aMCI and the
      control groups (all p<0.01). The DD genotype (23%) and D-allele (57%) frequencies
      in the aMCI patients were higher than those in the controls (16% vs. 43%). ACE
      genotype was correlated with delayed recall in Auditory Verbal Memory Test,
      delayed recall in Complex Figure Test, Category Fluency Test, and Symbol Digit
      Modalities Test in all subjects, in which the carriers of the DD and DI genotypes
      obtained lower scores than those of the II genotype (p<0.05). A significant
      difference in the serum ACE level was observed among the three genotypes
      (DD>DI>II) in both the aMCI and the control groups (all p<0.01). D-allele may be
      a genetic risk factor for the development of aMCI to Alzheimer's disease. A high
      serum ACE level possibly plays an important role in the incidence of aMCI.

PMID- 22405894
TI  - Differential plasticity of microglial cells in the rostrocaudal neuraxis of the
      accessory olfactory bulb of female mice following mating and stud male exposure.
AB  - The formation of an olfactory recognition memory by female mice for the stud male
      pheromones requires two fundamental conditions: incidence of mating and retention
      of the stud male with the female for a critical 6h interval following mating.
      This biologically critical recognition memory results from plasticity of
      reciprocal dendrodendritic synapses in the accessory olfactory bulb (AOB). In
      this study, a microglia marker antibody (ionized calcium-binding adaptor protein,
      Iba1) was used to determine how mating and stud pheromones affect microglia in
      the AOB rostrocaudal axis in female mice. The results showed that compared with
      estrus and mating only, mating and pheromone exposure significantly increased
      Iba1 immunoreactivity in the AOB evidenced by increased complexity of ramified
      microglial processes characteristic of resting microglial morphological
      phenotype, particularly in the rostral AOB. The density of Iba1 staining after
      mating and stud pheromone exposure was higher in the rostral - compared to caudal
      - AOB and was most prevalent in the external plexiform layer, the site of
      reciprocal mitral-granule dendrodendritic synapses. While cells with activated
      phenotype were observed in caudal AOB during estrus, mating/pheromone exposure
      appeared to induce a morphological transformation to the resting microglia
      phenotype. Since previous evidence implicate the rostral AOB in processing
      pheromonal signals and microglial cells monitor active synapses, these
      observations have important functional implications for a potential role for
      microglia in processing pheromonal signals in the AOB during the formation of
      olfactory memory.

PMID- 22405889
TI  - Tobacco addiction and the dysregulation of brain stress systems.
AB  - Tobacco is a highly addictive drug and is one of the most widely abused drugs in
      the world. The first part of this review explores the role of stressors and
      stress-associated psychiatric disorders in the initiation of smoking, the
      maintenance of smoking, and relapse after a period of abstinence. The reviewed
      studies indicate that stressors facilitate the initiation of smoking, decrease
      the motivation to quit, and increase the risk for relapse. Furthermore, people
      with depression or an anxiety disorder are more likely to smoke than people
      without these disorders. The second part of this review describes animal studies
      that investigated the role of brain stress systems in nicotine addiction. These
      studies indicate that corticotropin-releasing factor, Neuropeptide Y, the
      hypocretins, and norepinephrine play a pivotal role in nicotine addiction. In
      conclusion, the reviewed studies indicate that smoking briefly decreases
      subjective stress levels but also leads to a further dysregulation of brain
      stress systems. Drugs that decrease the activity of brain stress systems may
      diminish nicotine withdrawal and improve smoking cessation rates.

PMID- 22405895
TI  - Gliotoxin effects on fungal growth: mechanisms and exploitation.
AB  - Although initially investigated for its antifungal properties, little is actually
      known about the effect of gliotoxin on Aspergillus fumigatus and other fungi. We
      have observed that exposure of A. fumigatus to exogenous gliotoxin (14 MUg/ml),
      under gliotoxin-limited growth conditions, results in significant alteration of
      the expression of 27 proteins (up- and down-regulated >1.9-fold; p<0.05)
      including de novo expression of Cu, Zn superoxide dismutase, up-regulated
      allergen Asp f3 expression and down-regulated catalase and a peroxiredoxin
      levels. Significantly elevated glutathione GSH levels (p<0.05), along with
      concomitant resistance to diamide, were evident in A. fumigatus DeltagliT,
      lacking gliotoxin oxidoreductase, a gliotoxin self-protection gene. Saccharomyces
      cerevisiae deletents (Deltasod1 and Deltayap1) were hypersensitive to exogenous
      gliotoxin, while Deltagsh1 was resistant. Significant gliotoxin-mediated (5
      MUg/ml) growth inhibition (p<0.001) of Aspergillus nidulans, Aspergillus terreus,
      Aspergillus niger, Cochliobolus heterostrophus and Neurospora crassa was also
      observed. Growth of Aspergillus flavus, Fusarium graminearum and Aspergillus
      oryzae was significantly inhibited (p<0.001) at gliotoxin (10 MUg/ml), indicating
      differential gliotoxin sensitivity amongst fungi. Re-introduction of gliT into A.
      fumigatus DeltagliT, at a different locus (ctsD; AFUA_4G07040, an aspartic
      protease), with selection on gliotoxin, facilitated deletion of ctsD without use
      of additional antibiotic selection markers. Absence of ctsD expression was
      accompanied by restoration of gliT expression, and resistance to gliotoxin. Thus,
      we propose gliT/gliotoxin as a useful selection marker system for fungal
      transformation. Finally, we suggest incorporation of gliotoxin sensitivity assays
      into all future fungal functional genomic studies.

PMID- 22405897
TI  - Targeting neuronal adenylyl cyclase for the treatment of chronic pain.
AB  - Pain research is currently undergoing dramatic changes. In the area of basic pain
      research, new discoveries have been made towards the understanding of pain
      transmission, modulation and plasticity. However, many of these basic discoveries
      have not yet led to the development of new drugs for the treatment of chronic
      pain. One major reason for this disconnection is the lack of translational
      research and drug discovery based directly on the novel pain mechanism. In this
      review, I focus on activity-dependent potentiation in pain-related cortical areas
      and recent translational research on adenylyl cyclase subtype 1 (AC1) as a novel
      target for treating chronic pain. In particular, I discuss the AC1 inhibitor,
      NB001, which produces powerful analgesic effects in animal models of chronic pain
      by inhibiting chronic pain-related cortical potentiation.

PMID- 22405896
TI  - Molecular phylogeny and species delimitation in the section Longibrachiatum of
      Trichoderma.
AB  - The phylogenetically most derived group of the genus Trichoderma - section
      Longibrachiatum, includes some of the most intensively studied species, such as
      the industrial cellulase producer T. reesei (teleomorph Hypocrea jecorina), or
      the facultative opportunistic human pathogens T. longibrachiatum and H.
      orientalis. At the same time, the phylogeny of this clade is only poorly
      understood. Here we used a collection of 112 strains representing all currently
      recognized species and isolates that were tentatively identified as members of
      the group, to analyze species diversity and molecular evolution. Bayesian
      phylogenetic analyses based on several unlinked loci in individual and
      concatenated datasets confirmed 13 previously described species and 3 previously
      recognized phylogenetic species all of which were not yet described formally.
      When the genealogical concordance criterion, the K/theta method and comparison of
      frequencies of pairwise nucleotide differences were applied to the data sample,
      10 additional new phylogenetic species were recognized, seven of which consisted
      only of a single lineage. Our analysis thus identifies 26 putative species in
      section Longibrachiatum, what doubles the currently estimated taxonomic diversity
      of the group, and illustrates the power of combining genealogical concordance and
      population genetic analysis for dissecting species in a recently diverged group
      of fungal species.

PMID- 22405898
TI  - Current therapies in ischemic stroke. Part B. Future candidates in stroke therapy
      and experimental studies.
AB  - Stroke still remains a major healthcare problem. The growing understanding of the
      mechanism of cell death in ischemia leads to new approaches in stroke treatment.
      The aim of neuroprotection is to reduce the post-stroke impairment and the
      overall costs that are accompanied in patients with severe disability. Despite
      encouraging data from experimental animal models, almost all neuroprotective
      therapies have, to date, not been established in clinical routine. In this part B
      of our review on stroke therapies we provide an overview on future candidates in
      stroke therapy and neuroprotective agents that are under investigation.

PMID- 22405899
TI  - Relevance of systems pharmacology in drug discovery.
AB  - The pharmaceutical industry is in the process of re-inventing its pipeline in an
      attempt to overcome its increasing phase II and III attrition rates. Here, we
      describe how systems pharmacology can be used as a risk assessment tool to
      alleviate this problem before bringing in larger investments. We propose that
      this translational research tool could provide a valuable, complementary addition
      to other emerging innovative approaches for target identification and validation
      in discovery and, ultimately, for aiding clinical trial optimization.

PMID- 22405900
TI  - EPCA-2: a highly specific serum marker for prostate cancer.

PMID- 22405901
TI  - Focused ultrasound and interleukin-4 receptor-targeted liposomal doxorubicin for
      enhanced targeted drug delivery and antitumor effect in glioblastoma multiforme.
AB  - The clinical application of chemotherapy to brain tumors has been severely
      limited because the blood-brain barrier (BBB) often prevents therapeutic levels
      from being achieved. Here we show that pulsed HIFU and human atherosclerotic
      plaque-specific peptide-1 (AP-1)-conjugated liposomes containing doxorubicin (AP
      1 Lipo-Dox) act synergistically in an experimental brain tumor model. We
      developed an intracranial brain-tumor model in NOD-scid mice using human brain
      glioblastoma multiforme (GBM) 8401 cells. Pulsed HIFU was used to transcranially
      disrupt the BBB in these mouse brains by delivering ultrasound waves in the
      presence of microbubbles. Prior to each sonication, AP-1 Lipo-Dox or unconjugated
      Lipo-Dox was administered intravenously, and the concentration in the brains was
      quantified by fluorometer. Compared to control animals treated with injections of
      AP-1 Lipo-Dox or unconjugated Lipo-Dox, animals receiving the drug followed by
      pulsed HIFU exhibited enhanced accumulation of the drug in tumor cells. Drug
      injection with sonication increased the tumor-to-normal brain doxorubicin ratio
      of the target tumors by about twofold compared with the control tumors. Moreover,
      the tumor-to-normal brain ratio was highest after the injection of AP-1 Lipo-Dox
      with sonication. Combining sonication with AP-1 Lipo-Dox also significantly
      inhibited tumor growth compared with chemotherapy alone. There was a modest but
      significant increase in the median survival time in mice treated with AP-1 Lipo
      Dox followed by pulsed HIFU, compared to those treated with AP-1 Lipo-Dox without
      sonication. The use of AP-1-conjugated liposomes carrying cytotoxic agents
      followed by pulsed HIFU represents a feasible approach for enhanced targeted drug
      delivery in brain tumor therapies.

PMID- 22405902
TI  - Nanoscaled buffering zone of charged (PLGA)n-b-bPEI micelles in acidic
      microclimate for potential protein delivery application.
AB  - Poly(lactide-co-glycolide) (PLGA) has most often been employed for the controlled
      release of protein formulations because of its safety profile with non-toxic
      degradation products. Nevertheless, such formulations have been plagued by a
      local acidic microenvironment and protein-polymer interactions, which result in
      chemical and physical denaturation of loaded proteins and often unfavorable
      release profiles. This study investigated the pH change of inner PLGA microsphere
      (MS) using charged (PLGA)(n)-b-branched polyethyleneimine (bPEI) micelles. The
      designed micelles can be transformed into either micelle or reverse micelle (RM)
      depending on the solvent and RM can form microspheres. In addition, (PLGA)(n)-b
      bPEI can be modified into (PLGA)(n)-b-(carboxylated bPEI) via carboxylation of
      the primary amines. Cationic micelle (CM) or anionic micelle (AM) was complexed
      with counter-charged proteins leading to nanosized particles (approximately
      100nm). In the micelle/protein complexes, the micelles mostly maintained their
      proton buffering capacity, and consequently, prevented or delayed the typical
      decrease in pH caused by degradation of PLGA in aqueous solution. Reconstitutable
      micelle/protein complexes allowed for increased and fine-tuned protein loading
      (~20wt.% when using CM1 (CM prepared from PLGA(36kDa)-b-bPEI(25kDa))/insulin
      complexes) in PLGA MS. In CM2 (CM prepared from (PLGA(36kDa))(2)-b
      bPEI(25kDa))/insulin (4 of weight ratio (WR) of micelle to protein; WR4)-loaded
      PLGA MS, CM2 strongly prevented the micellar nanoenvironmental pH (pH 6.6 within
      5days and then approximately pH 8.5) to be acidified in PLGA MS for 9weeks,
      unlike CM2-free PLGA MS. In conclusion, our findings propose that the proton
      buffering capacity and protein loading in PLGA MS can be tuned by controlling the
      complexation ratios of micelles and proteins, polymeric architectures of
      (PLGA)(n)-b-bPEI copolymers and WR of micelle/protein complexes and PLGA (or RM).

PMID- 22405903
TI  - In vitro and in vivo performance of novel supersaturated self-nanoemulsifying
      drug delivery systems (super-SNEDDS).
AB  - Novel supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS)
      containing the poorly water-soluble drug halofantrine above equilibrium
      solubility (150% S(eq)) were compared in vitro and in vivo with conventional
      SNEDDS containing the drug below equilibrium solubility (75% S(eq)). Pre
      concentrates comprising of either medium chain lipids (Captex 300/Capmul MCM) or
      long chain lipids (soybean oil/Maisine), Cremophor RH40 and ethanol were
      formulated maintaining the lipid-to-surfactant-to-cosolvent ratio constant
      (55:35:10, w/w %). The ability of super-SNEDDS to increase the absorption of
      halofantrine in dogs, as well as the predictivity of the dynamic in vitro
      lipolysis model was studied. In vitro lipolysis of SNEDDS and super-SNEDDS showed
      rapid drug precipitation from all formulations while the same drug concentrations
      in the digestion medium were found during digestion of equal amounts of SNEDDS
      and super-SNEDDS. Elevated halofantrine solubilisation during in vitro lipolysis
      was observed only when multiple capsules of conventional SNEDDS were subjected to
      in vitro digestion. After lipolysis the isolated super-SNEDDS pellets were
      characterised by XRPD revealing no crystalline halofantrine from any of the
      investigated formulations. Subsequent dissolution studies of the super-SNEDDS
      pellet in the lipolysis medium demonstrated enhanced dissolution of halofantrine
      suggesting that halofantrine in the pellet was amorphous. The enhanced
      dissolution of the amorphous halofantrine was also reflected in vivo since two
      capsules of conventional SNEDDS were needed to achieve similar AUC and C(max) as
      obtained after dosing of a single capsule of super-SNEDDS. The study demonstrated
      that the absorption of halofantrine was not hampered by drug precipitation. Super
      SNEDDS lead to precipitation of halofantrine in an amorphous form, which can be
      the driving force for enhanced absorption. Since super-SNEDDS were also
      physically stable for at least 6 months they represent a potential novel oral
      lipid-based drug delivery system for low aqueous soluble compounds.

PMID- 22405904
TI  - Delivery of drugs to cell membranes by encapsulation in PEG-PE micelles.
AB  - Developing polymer micelles as drug delivery systems requires an in-depth
      understanding of how they interact with cells and deliver drugs across the cell
      membrane; however, this investigation faces many problems. In this study, we
      attempt to show how polyethylene glycol-phosphatidylethanolamine (PEG-PE)
      micelles deliver drugs across cell membranes by using a series of fluorescence
      techniques, including de-quenching, FRET and multi-labeling. We demonstrate that
      PEG-PE copolymers transfer to the cell membrane from micelles due to their
      amphiphilic properties, and are then internalized through nonspecific endocytosis
      and distributed in the endoplasmic reticulum and Golgi apparatus without
      affecting cellular ATP and viability. Hydrophilic drugs and/or hydrophobic dyes
      can be encapsulated in PEG-PE micelles, which are maintained in an intact form in
      culture medium before and after incubation with cells. These micelles disassemble
      and release their payloads at the cell membrane; released agents are accelerated
      to enter cells due to the increased membrane fluidity caused by PEG-PE insertion.
      Encapsulation of drugs in micelles does not change their intracellular
      distribution but increases their cellular accumulation. This investigation
      provides new insights into the mechanism of polymer micelle delivering drugs into
      cells, which are helpful for designing a true site-specific delivery carrier.

PMID- 22405905
TI  - Selective conjugation of poly(2-ethyl 2-oxazoline) to granulocyte colony
      stimulating factor.
AB  - Poly(2-ethyl 2-oxazoline) (PEOZ) is a water-soluble, stable and biocompatible
      polymer that was prepared in a linear form for the conjugation of protein
      biomolecules. Polymers of molecular weights ranging from 5 to 20 kDa, with an
      aldehyde or an amine functional terminal group, were synthesized with narrow
      polydispersities. To assess the suitability of the polymer for therapeutic
      application, granulocyte colony stimulating factor (G-CSF) was used as a model
      protein for PEOZ conjugation. Two coupling strategies were employed, namely the
      chemical N-terminal reductive amination and the enzymatic transglutaminase
      (TGase) mediated glutamine conjugation. The secondary structure of the protein,
      measured by circular dichroism, was maintained upon PEOZylation and the stability
      of conjugates toward aggregation at 37  degrees C was improved compared to G-CSF.
      The potency of PEOZ-G-CSF mono-conjugates was tested in vitro by cell
      proliferation assays and in vivo by studying the effects on white blood cell and
      neutrophil count increases in normal rats. The results have shown that PEOZ is
      suitable for protein conjugation by both chemical and enzymatic methods and that
      the conjugates of G-CSF retained high biological activity, both in vitro and in
      vivo.

PMID- 22405906
TI  - Culturing and molecular methods to assess the infectivity of porcine circovirus
      from treated effluent of swine manure.
AB  - Samples were collected at the effluent of two swine manure treatment systems and
      were analyzed by qPCR to determine the presence and amounts of porcine circovirus
      (PCV2) genetic material. ST cells were inoculated with the positive samples to
      evaluate virus viability and for viral genotyping. Twenty-five water samples were
      collected monthly from treated effluent (March 2009 to December 2010). The PCV2
      genome was identified by qPCR in 60% of the samples, and all of the positive
      samples were able to infect ST cells in vitro. Positive samples were genotyped
      and 60% of them were positive for both PCV2a and PCV2b, 20% were positive for
      genotype 2a, and 20% were positive for genotype 2b. Our results suggest that
      these viruses were able to resist the regular wastewater treatment, and this
      finding demonstrates the necessity of adding a virus inactivation step to the
      treatment system to guarantee the safety of water reuse.

PMID- 22405907
TI  - Susceptibility of Trypanosoma evansi to propolis extract in vitro and in
      experimentally infected rats.
AB  - Current therapy of Trypanosoma evansi infections is not effective for the vast
      majority of animals with relapsing parasitemia and clinical signs. Recently,
      attention is being focused on the antiparasitic activity of propolis. This study
      evaluated the susceptibility of T. evansi to propolis extract in vitro and in
      vivo. A dose-dependent trypanocidal activity of propolis extract was observed in
      vitro. All trypomastigotes were killed 1 h after incubation with 10 MUg mL(-1) of
      the extract. In vivo, the concentrations of 100, 200, 300 and 400 mg kg(-1)
      administered orally for 10 consecutive days showed no curative effect, and the
      rats died from the disease. However, rats treated with the two highest
      concentrations of propolis extract showed higher longevity than the other groups.
      Based on these data, we concluded that T. evansi is susceptible to propolis in
      vitro. Despite the lack of curative efficacy observed in vivo at the
      concentrations tested, the propolis extract can prolong life in rats infected
      with the protozoan.

PMID- 22405908
TI  - Development of real-time assays for impedance-based detection of microbial double
      stranded DNA targets: optimization and data analysis.
AB  - A real-time, label free assay was developed for microbial detection, utilizing
      double-stranded DNA targets and employing the next generation of an impedimetric
      sensor array platform designed by Sharp Laboratories of America (SLA). Real-time
      curves of the impedimetric signal response were obtained at fixed frequency and
      voltage for target binding to oligonucleotide probes attached to the sensor array
      surface. Kinetic parameters of these curves were analyzed by the integrated data
      analysis package for signal quantification. Non-specific binding presented a
      major challenge for assay development, and required assay optimization. For this,
      differences were maximized between binding curve kinetic parameters for probes
      binding to complementary targets versus non-target controls. Variables
      manipulated for assay optimization included target concentration, hybridization
      temperature, buffer concentration, and the use of surfactants. Our results showed
      that (i) different target-probe combinations required optimization of specific
      sets of variables; (ii) for each assay condition, the optimum range was
      relatively narrow, and had to be determined empirically; and (iii) outside of the
      optimum range, the assay could not distinguish between specific and non-specific
      binding. For each target-probe combination evaluated, conditions resulting in
      good separation between specific and non-specific binding signals were
      established, generating high confidence in the SLA impedimetric dsDNA assay
      results.

PMID- 22405909
TI  - Antihypertensive effect and antioxidant activity of peptide fractions extracted
      from Spanish dry-cured ham.
AB  - This study examined the antihypertensive and antioxidant activities of water
      soluble fractions of a Spanish dry-cured ham extract. Antihypertensive activity
      of a fractionated peptide extract, by size-exclusion chromatography was
      determined by measuring changes in systolic blood pressure of spontaneously
      hypertensive rats after oral administration. Every sample exhibited
      antihypertensive activity, pooled fractions corresponding to 1700 Da or lower
      were the most antihypertensive with a decrease of 38.38 mm Hg in systolic blood
      pressure. In vitro experiments revealed marked in vitro angiotensin I-converting
      enzyme inhibitory activity in fractions corresponding to these elution volumes.
      Some of the fractions exhibited great 1,1-diphenyl-2-picrylhydrazyl radical
      scavenging activity, ranging from 39% to 92% as well as superoxide ion
      extinguishing ability with values ranging from 41.67% to 50.27% of the
      antioxidant activity, suggesting the presence of peptides with antioxidant
      activity. These findings suggest that Spanish dry-cured ham contains peptides
      with antioxidant and antihypertensive activities.

PMID- 22405910
TI  - Response surface optimization of effects of some processing variables on
      carcinogenic/mutagenic heterocyclic aromatic amine (HAA) content in cooked
      patties.
AB  - A five-factor Central Composite Orthogonal Design was adopted to study
      simultaneous effects of some processing variables such as NaCl (0-2%), fat (10
      30%), ascorbic acid (0-600 ppm), cooking temperature (150-230 degrees C) and
      cooking time (5-15 min) on physicochemical properties and heterocyclic aromatic
      amine (HAA) contents of cooked beef patties. The HAAs analyzed were 2-amino-3
      methylimidazo[4,5-f]-quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]
      quinoxaline (MeIQx), 2-amino-3,4-dimethylimidazo[4,5-f]-quinoline (MeIQ), 2-amino
      3,4,8-trimethylimidazo[4,5-f]-quinoxaline (4,8-DiMeIQx) and 2-amino-1-methyl-6
      phenylimidazo[4,5-b]-pyridine (PhIP), as quantified by high-performance liquid
      chromatography with photo-diode array detection (HPLC-UV/DAD). It was found that
      ascorbic acid decreased; however, fat, cooking temperature and time levels
      increased the contents of IQ, MeIQx, MeIQ and PhIP. In addition, estimated ridge
      analysis was conducted to find values of the processing variables that maximize
      and minimize the five HAA contents, revealing that the results obtained would be
      useful for meat industry aiming to decrease HAA content in cooked meat products.

PMID- 22405911
TI  - Cull sow knife-separable lean content evaluation at harvest and lean mass content
      prediction equation development.
AB  - The objectives of this study were to develop a prediction equation for carcass
      knife-separable lean within and across USDA cull sow market weight classes (MWC)
      and to determine carcass and individual primal cut knife separable lean content
      from cull sows. There were significant percent lean and fat differences in the
      primal cuts across USDA MWC. The two lighter USDA MWC had a greater percent
      carcass lean and lower percent fat compared to the two heavier MWC. In general,
      hot carcass weight explained the majority of carcass lean variation.
      Additionally, backfat was a significant variation source when predicting cull sow
      carcass lean. The findings support using a single lean prediction equation across
      MWC to assist processors when making cull sow purchasing decisions and determine
      the mix of animals from various USDA MWC that will meet their needs when making
      pork products with defined lean:fat content.

PMID- 22405912
TI  - Antihypertensive activity of peptides identified in the in vitro gastrointestinal
      digest of pork meat.
AB  - This study investigated the in vivo antihypertensive activity of three novel
      peptides identified in the in vitro digest of pork meat. These peptides were RPR,
      KAPVA and PTPVP and all of them showed significant antihypertensive activity
      after oral administration to spontaneously hypertensive rats, RPR being the
      peptide with the greatest in vivo activity. To our knowledge, this is the first
      report showing the in vivo antihypertensive action of the three peptides from
      nebulin (RPR) and titin (KAPVA and PTPVP), thus confirming their reported in
      vitro angiotensin I-converting enzyme (ACE) inhibitory activity. These findings
      suggest that pork meat could constitute a source of bioactive constituents that
      could be utilized in functional foods or nutraceuticals.

PMID- 22405913
TI  - Halal authenticity issues in meat and meat products.
AB  - In the recent years, Muslims have become increasingly concerned about the meat
      they eat. Proper product description is very crucial for consumers to make
      informed choices and to ensure fair trade, particularly in the ever growing halal
      food market. Globally, Muslim consumers are concerned about a number of issues
      concerning meat and meat products such as pork substitution, undeclared blood
      plasma, use of prohibited ingredients, pork intestine casings and non-halal
      methods of slaughter. Analytical techniques which are appropriate and specific
      have been developed to deal with particular issues. The most suitable technique
      for any particular sample is often determined by the nature of the sample itself.
      This paper sets out to identify what makes meat halal, highlight the halal
      authenticity issues that occur in meat and meat products and provide an overview
      of the possible analytical methods for halal authentication of meat and meat
      products.

PMID- 22405914
TI  - Prediction of pork quality with near infrared spectroscopy (NIRS) 2. Feasibility
      and robustness of NIRS measurements under production plant conditions.
AB  - Longissimus dorsi samples (685) collected at four processing plants were used to
      develop prediction equations for meat quality with near infrared spectroscopy.
      Equations with R(2)>0.70 and residual prediction deviation (RPD)>=2.0 were
      considered as applicable for screening. One production plant showed R(2) 0.76 and
      RPD 2.05, other plants showed R(2)<0.70 and RPD<2.0 for drip loss %. RPD values
      were <=2.05 for drip loss%, for colour L*<=1.82 and pH ultimate (pHu)<=1.57.
      Samples were grouped for drip loss%; superior (<2.0%), moderate (2-4%), inferior
      (>4.0%). 64% from the superior group and 56% from the inferior group were
      predicted correctly. One equation could be used for screening drip loss %. Best
      prediction equation for L* did not meet the requirements (R(2) 0.70 and RPD
      1.82). pHu equation could not be used. Results suggest that prediction equations
      can be used for screening drip loss %.

PMID- 22405915
TI  - Clinical outcome after suture anchor repair for complete traumatic rupture of the
      distal triceps tendon.
AB  - PURPOSE: To evaluate the clinical results of surgical repair of complete distal
      triceps tendon rupture using suture anchors and high-strength sutures by use of
      validated outcome measures. METHODS: A consecutive series of traumatic distal
      triceps tendon ruptures at a single institution were studied. All cases were
      surgically repaired by use of suture anchors double loaded with ultrahigh
      molecular-weight polyethylene-containing sutures. All patients were evaluated
      with a physical examination, radiographs, and questionnaires. The following
      postoperative validated outcome measures were used: the Disabilities of the Arm,
      Shoulder and Hand (DASH) score; the Oxford Elbow Score; the American Shoulder and
      Elbow Surgeons elbow assessment form; and the Mayo Elbow Performance Index.
      RESULTS: Five male patients with a mean follow-up of 32 months underwent suture
      anchor repair for traumatic rupture of the distal triceps tendon. Of the repairs,
      3 were in the dominant arm and 2 in the nondominant arm. The mean patient age was
      47 years (range, 35 to 54 years). Postoperatively, the mean DASH score was 1.4,
      the mean American Shoulder and Elbow Surgeons elbow score was 99.2, the mean Mayo
      Elbow Performance Index was 95.8, the mean Oxford Elbow Score for pain was 98.8,
      the mean Oxford Elbow Score for function was 100, and the mean Oxford Elbow Score
      for the social domain was 96.2. A lower score for the DASH indicates less
      disability and better function. CONCLUSIONS: This retrospective case series of
      suture anchor repair of distal triceps tendon ruptures showed excellent elbow
      function based on validated clinical outcome measures. LEVEL OF EVIDENCE: Level
      IV, therapeutic case series.

PMID- 22405916
TI  - Arthroscopic management of proximal humerus malunion with tuberoplasty and
      rotator cuff retensioning.
AB  - PURPOSE: To report the mid- to long-term results of arthroscopic tuberoplasty and
      rotator cuff retensioning for proximal humerus malunion. METHODS: Between August
      2001 and October 2009, 9 patients with a mean age of 49 years underwent shoulder
      arthroscopy with tuberoplasty and rotator cuff advancement for malunion of the
      proximal humerus and were included in this study. The mean delay between the
      initial fracture and our surgery was 19 months. We developed a systematic
      technique to take down the rotator cuff over the malunited proximal humerus,
      perform a tuberoplasty, and then retension and repair the rotator cuff by
      advancing it on the greater tuberosity. The mean follow-up was 50 months (range,
      12 to 108 months). RESULTS: Patients showed mean active forward elevation of 164
      degrees  (range, 90 degrees  to 180 degrees ; gain of 43 degrees ), recovery of
      mean active external rotation of 45 degrees  (range, 30 degrees  to 60 degrees ;
      gain of 16 degrees ), and a mean pain score of 1.8 points (range, 0 to 5 points;
      reduction of 3.8 points). The overall functional results according to the
      University of California, Los Angeles score were excellent in 3 cases, good in 3,
      and fair in 3. No patient required additional surgery. Of the 9 patients, 8 (89%)
      were able to return to their previous sports or activities. All patients declared
      themselves as being satisfied with the result. CONCLUSIONS: Arthroscopic
      tuberoplasty and rotator cuff retensioning for proximal humerus malunion comprise
      a viable alternative to traditional open methods, particularly in young patients.
      A comprehensive approach is recommended that addresses stiffness, associated
      pathology, and impingement, and re-establishes rotator cuff function. Although
      the technique is technically demanding, it allows preservation of the native
      humeral head, is associated with a very low complication rate, and avoids
      concerns about long-term prosthetic survival in young patients. LEVEL OF
      EVIDENCE: Level IV, therapeutic case series.

PMID- 22405917
TI  - Loss of expression of the cancer stem cell marker aldehyde dehydrogenase 1
      correlates with advanced-stage colorectal cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) progression is mediated by cancer stem cells
      (CSCs). We sought to determine if the expression of the CSC marker aldehyde
      dehydrogenase 1 (ALDH1) in CRC tumors varies by American Joint Committee on
      Cancer stage or correlates to clinical outcomes. METHODS: Primary and metastatic
      CRC samples from 96 patients were immunostained with antibodies to ALDH1 and
      imaged to evaluate marker expression. The percentage of ALDH1(+) cells was
      correlated to clinical outcomes. RESULTS: ALDH1 was overexpressed in CRC tumors
      compared with nonneoplastic tissue. Marker expression was highest in
      nonmetastatic tumors. The loss of expression was associated with advanced stage
      and metastatic disease. No significant correlation was found between ALDH1
      expression and metastasis, recurrence, or survival. CONCLUSIONS: ALDH1 was highly
      expressed in nonmetastatic CRC, but expression was lost with advancing stage.
      ALDH1 could be an effective therapeutic target in early CRC but not late-stage
      disease. No correlation was found between ALDH1 and disease prognosis.

PMID- 22405918
TI  - The duodenal switch for morbid obesity: modification of cardiovascular risk
      markers compared with standard bariatric surgeries.
AB  - BACKGROUND: Obesity is associated with cardiovascular risk factors such as lipid
      levels and increased levels of C-reactive peptide (CRP). We hypothesized that
      duodenal switch (DS) would show equivalent or superior risk reduction compared
      with standard bariatric surgeries. METHODS: Patients underwent DS, sleeve
      gastrectomy (SG), or gastric bypass (GB) over a 2-year period. Body mass index
      (BMI), lipid panel, and CRP were measured preoperatively and then 3, 6, and 12
      months postoperatively. RESULTS: A total of 130 patients were identified; 42
      underwent DS, 40 underwent SG, and 48 underwent GB. All groups had similar sex
      and comorbidity profiles, but the mean preoperative BMI was greatest in the DS
      group (mean = 52). At all intervals weight loss was greater in the DS group (P <
      .01), with a final BMI of 31 for the DS group, 31 for the SG group, and 28 for
      the GB group. Cholesterol and low-density lipoprotein showed significantly
      greater improvement at all time points with DS compared with SG and GB (P < .01).
      Baseline CRP levels among DS patients were double that of SG and GB, but rapidly
      declined to equivalent levels by 3 months and normalized in 79%. CONCLUSIONS: The
      DS procedure resulted in a superior reduction in cardiovascular and
      proinflammatory risk markers compared with GB and SG.

PMID- 22405919
TI  - Synthesis and biological evaluation of benzoisothiazole derivatives possessing
      N,N-dimethylformimidamide group as 5-HT6 receptor antagonists.
AB  - A series of novel N,N-dimethyl-N'-(5-(Ar-sulfonamido) benzo[d]isothiazol-3
      yl)formimidamides was designed and synthesized as 5-HT(6) ligands. Here N,N
      dimethyl formimidamides was used as a replacement for an aminoethyl moiety. In
      vitro functional assays demonstrated compounds 9b and 9i significantly inhibited
      the 5-HT-induced Ca(2+) increases (9b; IC(50)=0.36 MUM and 9i; IC(50)=0.44 MUM),
      indicating that 9b and 9i were potent 5-HT(6) receptor antagonists. Compounds 9i
      also showed good selectivity on the 5-HT(6) over 5-HT(4) and 5-HT(7) receptors.

PMID- 22405921
TI  - Development of programmable small DNA-binding molecules with epigenetic activity
      for induction of core pluripotency genes.
AB  - Epigenetic modifications that govern the gene expression are often overlooked
      with the design of artificial genetic switches. N-Methylpyrrole-N-methylimidazole
      (PI) hairpin polyamides are programmable small DNA binding molecules that have
      been studied in the context of gene regulation. Recently, we synthesized a
      library of compounds by conjugating PI polyamides with SAHA, a chromatin
      modifier. Among these novel compounds, PI polyamide-SAHA conjugate 1 was shown to
      epigenetically activate pluripotency genes in mouse embryonic fibroblasts. Here,
      we report the synthesis of the derivatives of conjugate 1 and demonstrate that
      these epigenetically active molecules could be developed to improve the induction
      of pluripotency factors.

PMID- 22405920
TI  - Synthesis of pdCpAs and transfer RNAs activated with thiothreonine and
      derivatives.
AB  - N,S-diprotected L-thiothreonine and L-allo-thiothreonine derivatives were
      synthesized using a novel chemical strategy, and used for esterification of the
      dinucleotide pdCpA. The aminoacylated dinucleotides were then employed for the
      preparation of activated suppressor tRNA(CUA) transcripts. Thiothreonine and allo
      thiothreonine were incorporated into a predetermined position of a catalytically
      competent dihydrofolate reductase (DHFR) analogue lacking cysteine, and the
      elaborated proteins were derivatized site-specifically at the thiothreonine
      residue with a fluorophore.

PMID- 22405922
TI  - New insights into the structure-cytotoxicity relationship of spirostan saponins
      and related glycosides.
AB  - A variety of spirostan saponins and related glycosides were synthesized and
      evaluated for their cytotoxicity against the human myeloid leukemia cell line (HL
      60). A linear glycosylation strategy allowed for accessing a variety of
      functionalization patterns at both the spirostanic and the saccharide moieties,
      which provides new information regarding the structure-cytotoxicity relationship
      of this family of steroidal glycosides. Intriguing results were achieved with
      respect to hecogenyl and 5alpha-hydroxy-laxogenyl beta-chacotriosides, turning
      out to be the former very cytotoxic and the latter no cytotoxic at all.
      Importantly, the partially pivaloylated beta-d-glucosides of 5alpha-hydroxy
      laxogenin were the most potent cytotoxic compounds among all tested glycosides.
      This comprises the first report on acylated spirostanyl glucosides displaying
      significant cytotoxicity, and therefore, it opens up new opportunities toward the
      development of saponin analogues as anticancer agents.

PMID- 22405923
TI  - The use of procedural knowledge in simple addition and subtraction problems.
AB  - In a first experiment, adults were asked to solve one-digit additions,
      subtractions and multiplications. When the sign appeared 150 ms before the
      operands, addition and subtraction were solved faster than when the sign and the
      operands appeared simultaneously on screen. This priming effect was not observed
      for multiplication problems. A second experiment replicates these results on
      addition and multiplication and, moreover, shows that the priming effect in
      addition is observed for all problems, including very small ones such as 4+3. In
      fact, the only problems that were not primed by the addition sign were tie
      problems, which confirms that they have a special status in memory. Taken
      together, these results suggest that abstract procedures are pre-activated by the
      addition and subtraction signs and that these procedures are consequently used by
      adults to solve the problems. No such procedures would be pre-activated for
      multiplication, which are then most probably solved by retrieval of the result
      from memory. Moreover, while obviously two different strategies were used by
      individuals in order to solve addition and multiplication, solution times were
      similar when the problems were presented in their whole. These results, which
      question most of the conclusions of the current literature, support Anderson's
      model (1982) and Baroody's assumptions (1983) on the existence of compacted
      procedures that could be as fast as retrievals.

PMID- 22405924
TI  - What we say and what we do: the relationship between real and hypothetical moral
      choices.
AB  - Moral ideals are strongly ingrained within society and individuals alike, but
      actual moral choices are profoundly influenced by tangible rewards and
      consequences. Across two studies we show that real moral decisions can
      dramatically contradict moral choices made in hypothetical scenarios (Study 1).
      However, by systematically enhancing the contextual information available to
      subjects when addressing a hypothetical moral problem-thereby reducing the
      opportunity for mental simulation-we were able to incrementally bring subjects'
      responses in line with their moral behaviour in real situations (Study 2). These
      results imply that previous work relying mainly on decontextualized hypothetical
      scenarios may not accurately reflect moral decisions in everyday life. The
      findings also shed light on contextual factors that can alter how moral decisions
      are made, such as the salience of a personal gain.

PMID- 22405925
TI  - Isoform-specific immunolocalization of 14-3-3 proteins in atherosclerotic lesions
      of human carotid and main cerebral arteries.
AB  - 14-3-3 proteins are now recognized to have a wide range of potential functions
      and pathological relevance, such as regulating the intercellular signal processes
      of differentiation, the development and growth of cells, or preventing or
      mediating cell apoptosis and survival by controlling the localization of
      potential signaling molecules. We investigated the immunolocalization of 14-3-3
      proteins in atherosclerotic lesions of human cerebral and carotid arteries using
      14-3-3 isoform-specific antibodies to distinguish 7 isoforms, and confirmed the
      cell type localization using double immunofluorolabeling. 14-3-3 common (COM)
      like immunoreactivity (IR) was intense, mainly in the foam cells and
      multinucleated giant cells of the carotid artery. The beta, gamma, epsilon, tau,
      eta, and zeta (6/7) isoform-specific antibodies showed similar results to those
      with anti-14-3-3 COM antibody. However, among these isoform-specific antibodies,
      the anti-eta isoform antibody most intensely immunolabeled multinucleated giant
      cells and foam cells, and the anti-zeta isoform antibody most intensely
      immunolabeled infiltrating vascular smooth muscle cells (VSMCs), in carotid
      plaques. Zeta IR was also observed in one part of the mural thrombus and in the
      nuclei of foam cells. Gamma isoform-like IR was relatively limited in cell
      components, but extracellular lesions were partly positive for this isoform. In
      the main cerebral arteries, the anti-epsilon isoform antibody most intensely
      immunolabeled infiltrating VSMCs in the intima of thickened fibrous cap plaques.
      Endothelial cells were also positive for the epsilon isoform. These findings may
      provide a basis for understanding the isoform-specific role associated with
      atherosclerotic lesions of the cerebral and carotid arteries.

PMID- 22405926
TI  - Variable results after rituximab in neuromyelitis optica.
AB  - Our objective was to assess the efficacy of rituximab (RTX) in neuromyelitis
      optica (NMO). We conducted a retrospective review of cases personally treated by
      the authors. We identified nine subjects meeting criteria for either NMO or
      recurrent longitudinally extensive transverse myelitis (LETM) who were treated
      with RTX and documented their clinical course. Six of the nine subjects continued
      to have relapses after RTX treatment. RTX was the first immunosuppressive
      treatment used after diagnosis in five subjects, and four of these continued to
      have relapses. We conclude that outcomes after RTX treatment of NMO are
      inconsistent. The observed variability may reflect differences in disease
      activity between individuals, differences in disease activity over time, or
      differences in the underlying immunopathogenesis of NMO. More effective
      treatments are needed.

PMID- 22405927
TI  - Analysis of JAG1 gene variant in Chinese patients with Alagille syndrome.
AB  - Alagille syndrome (AGS) is an autosomal dominant disorder characterized by bile
      duct paucity. It can be caused by variations in the JAG1 gene encoding a protein
      of Notch ligand and by variations in the NOTCH2 gene encoding a Notch receptor.
      In this study we identified 15 different JAG1 gene variations in 17 Chinese
      patients, nine of which were novel alterations including c.766G > T, c.819delC,
      c.826delT, c.3099_3100delCA, c.1323_1326delCTGG, c.1771_1775delGTGCGinsT,
      c.1868delG, c. 2791_2792insA and c.866delG. These alterations were located in the
      extracellular domain of JAG1, in particular in the DSL and EGF-like repeat
      domain. All the specific variations in five inheritance cases investigated were
      de novo. Furthermore, no sequence variation of NOTCH2 was detected in JAG1
      alteration negative patients.

PMID- 22405928
TI  - POLG mutation in a patient with cataracts, early-onset distal muscle weakness and
      atrophy, ovarian dysgenesis and 3-methylglutaconic aciduria.
AB  - Mutations in POLG account for one of the most frequent nuclear encoded causes of
      mitochondrial disorders to date. Individuals harboring POLG mutations exhibit
      fairly heterogeneous clinical presentations leading to increasing difficulties in
      classifying these patients into defined clinical phenotypes. This study aims to
      investigate the molecular basis of a mitochondrial cytopathy in a patient with 3
      methylglutaconic aciduria and to expand the clinical phenotype associated with
      POLG mutations. Clinical, molecular and genetic analyses as well as
      neurophysiological examinations were carried out for a 23-year-old woman of mixed
      Caucasian and Latin American ancestry with a history of cataracts diagnosed at
      age 1 year, she had onset of distal muscle weakness at age 2 years progressing to
      atrophy and ovarian dysgenesis at puberty. The patient was found to have 3
      methylglutaconic acid with normal 3 hydroxyisovaleric acid on urine organic acid
      analysis. POLG sequencing was done and a heterozygous variant, c.2851T>A
      (p.Y951N) was found which is predicted to be deleterious. There are limited
      reports of POLG mutations in individuals with 3-methylglutaconic aciduria. This
      case report of a young woman with a heterozygous mutation in POLG, presenting
      with muscle weakness and atrophy at a young age aims to aid clinicians in similar
      challenging diagnostic situations as well as enhances our understanding of POLG
      related disease phenotypes.

PMID- 22405929
TI  - Investigation on the transcription factors of porcine 3beta-hydroxysteroid
      dehydrogenase and 17beta-hydroxysteroid dehydrogenase genes.
AB  - The enzymes 3beta-hydroxysteroid dehydrogenase (3betaHSD) and 17beta
      hydroxysteroid dehydrogenase (17betaHSD) regulate the steroid metabolism in
      mammals. In this study, we aimed to characterize the steroid related
      transcription factors at the 5' flanking region of these two genes. A series of
      5' deletions of approximately 1 kb of 5'-flanking region on both genes were fused
      to a pGL3 basic vector containing firefly luciferase cDNA, and then transfected
      to human hepatocellular liver carcinoma cell line (HepG2). Luciferase activity
      assay indicated the region from -574 to -617 bp of the 3betaHSD1 promoter, and
      from -850 to -868 bp of 17betaHSD7 promoter induced the highest luciferase
      activity. A putative transcription factor, i.e. the proline and acidic amino acid
      rich basic leucine zipper (PAR/bZIP) family of 3betaHSD1 gene, and three-amino
      acid loop extension (TALE) homeodomain class of 17betaHSD7 were identified
      respectively by sequence homology. Gel shift assay further confirmed the binding
      capacity of the putative elements to nuclear extract. Our study gives new
      insights to the transcriptional regulation of 3betaHSD1 and 17betaHSD7 and
      further hints to their involvement in steroid metabolism.

PMID- 22405930
TI  - Basolateral amygdala lesions attenuate safe taste memory-related c-fos expression
      in the rat perirhinal cortex.
AB  - Previous results indicated that damage and pharmacological inactivation of the
      basolateral amygdala (BLA) interfere with the attenuation of taste neophobia. A
      similar disruption of safe taste memories formation induced by the inhibition of
      protein synthesis in the perirhinal cortex (PRh) has been reported. Thus, we have
      assessed the effect of bilateral BLA neurotoxic lesions on PRh activity after
      novel and familiar taste exposure. Wistar male rats with NMDA lesions of the BLA
      and SHAM-operated received two consecutive exposures to a 3% cider vinegar
      solution. Fos-like immunoreactivity (FLI) was examined as a marker of neuronal
      activity in PRh. As expected the BLA lesioned group showed no evidence of
      neophobia attenuation. A similar number of PRh Fos-positive cells were found in
      SHAM and BLA groups exposed to the novel taste solution. However, the BLA
      lesioned group exhibited a lower number of Fos stained cells than the SHAM
      lesioned group after being exposed to the familiar taste solution. This supports
      the notion of BLA and PRh as components of a neural circuit involved in safe
      taste recognition memory and suggests a role of PRh in various forms of
      recognition memory.

PMID- 22405932
TI  - Evaluation of saliva collection devices for the analysis of proteins.
AB  - BACKGROUND: Human saliva mirrors the body's health and can be collected non
      invasively, does not require specialized skills and is suitable for large
      population based screening programs. The aims were twofold: to evaluate the
      suitability of commercially available saliva collection devices for quantifying
      proteins present in saliva and to provide levels for C-reactive protein (CRP),
      myoglobin, and immunoglobin E (IgE) in saliva of healthy individuals as a
      baseline for future studies. METHODS: Saliva was collected from healthy
      volunteers (n=17, ages 18-33years). The following collection methods were
      evaluated: drool; Salimetrics(r) Oral Swab (SOS); Salivette(r) Cotton and
      Synthetic (Sarstedt) and Greiner Bio-One Saliva Collection System (GBO SCS(r)).
      We used AlphaLISA(r) assays to measure CRP, IgE and myoglobin levels in human
      saliva. RESULTS: Significant (p<0.05) differences in the salivary flow rates were
      observed based on the method of collection, i.e. salivary flow rates were
      significantly lower (p<0.05) in unstimulated saliva (i.e. drool and SOS), when
      compared with mechanically stimulated methods (p<0.05) (Salivette(r) Cotton and
      Synthetic) and acid stimulated method (p<0.05) (SCS(r)). Saliva collected using
      SOS yielded significantly (p<0.05) lower concentrations of myoglobin and CRP,
      whilst, saliva collected using the Salivette(r) Cotton and Synthetic swab yielded
      significantly (p<0.05) lower myoglobin and IgE concentrations respectively.
      CONCLUSIONS: The results demonstrated significantly relevant differences in
      analyte levels based on the collection method. Significant differences in the
      salivary flow rates were also observed depending on the saliva collection method.
      The data provide preliminary baseline values for salivary CRP, myoglobin, and IgE
      levels in healthy participants and based on the collection method.

PMID- 22405931
TI  - A network meta-analysis of therapies for previously untreated chronic lymphocytic
      leukemia.
AB  - BACKGROUND: Several therapy options are available for symptomatic, treatment
      naive chronic lymphocytic leukemia (CLL). Many of these therapies have been
      compared against chlorambucil, but have not been directly compared against each
      other. There is currently no agreed upon standard therapeutic regimen for
      treatment-naive CLL. METHODS: We performed a systematic literature review to
      identify randomized controlled trials (RCTs) published prior to November 2011 of
      therapies for previously untreated CLL. We conducted a network meta-analysis
      using fixed and random effect statistical models to estimate differences between
      shape and scale parameters of progression-free survival (PFS) curves for each
      competing therapy. We used the parameter estimates and a Weibull distribution to
      project mean PFS for each therapy option. RESULTS: Five RCTs were included in our
      comparison network. Overall, patients were younger (59-65 years), had good
      performance status based on the Eastern Cooperative Oncology Group scale (ECOG 0
      1), and earlier stage disease (Rai 0-II or Binet A or B). The combination regimen
      fludarabine with cyclophosphamide and rituximab (FCR) was estimated to yield mean
      PFS of 76 months (95% CrI: 60, 91), FC 60 months (46, 73), fludarabine 38 months
      (27, 49), alemtuzumab 24 months (15, 32), and chlorambucil 23 months (15, 32).
      CONCLUSION: Our results suggest that FCR has relatively higher potential of
      preventing disease progression in younger, healthier, treatment-naive CLL
      patients and should be considered an optimal initial treatment strategy for this
      patient population. However, because estimates are based on model simulation,
      additional studies of FCR are necessary to clinically validate its therapeutic
      potential.

PMID- 22405933
TI  - R450H TSH receptor mutation in congenital hypothyroidism in Taiwanese children.
AB  - BACKGROUND: The most common congenital endocrine disorder, congenital
      hypothyroidism (CHT), is strongly associated with thyroid hormone deficiency.
      Previous studies have indicated that mutations of thyroid stimulation hormone
      receptor (TSHR) are a risk factor for the development of congenital
      hypothyroidism. One mutation of TSHR, p.R450H, is particularly frequent in
      Japanese children with CHT. However, the frequency of this TSHR mutation among
      Taiwanese patients with CHT is unclear. METHODS: We enrolled 149 CHT patients and
      334 healthy subjects who volunteered to participate in health screening
      examinations. We characterized the clinical status of CHT patients with the TSHR
      mutations. RESULTS: There was a significant association between the TSHR mutation
      (p.R450H) and the risk of CHT (P=0.0008 under the dominant model and P=0.0002
      under the allelic model). The frequency of homozygous p.R450H in the CHT patients
      was 1.4% and that of heterozygous p.R450H was 5.6%. All five patients had
      elevated serum TSH levels. However, there was no difference in TSH levels between
      those with heterozygous and homozygous p.R450H mutations. CONCLUSION:
      Approximately 7% of the patients in this study with CHT had heterozygous or
      homozygous TSHR mutations (c.1349G>A, p.R450H). Consistent with previous reports
      on Japanese populations, this mutation was relatively important in the Taiwanese
      children with CHT.

PMID- 22405934
TI  - Porcine arthrogryposis multiplex congenita (AMC): new diagnostic test and
      narrowed candidate region.
AB  - In the Swiss Large White pig population a genetically caused arthrogryposis
      multiplex congenita (AMC) variant was identified. The disease is autosomal
      recessively inherited and is a fatal defect. Affected piglets are of normal size,
      but show malformed and permanently contracted joints in their legs. Often the
      spinal cord is curved and the lower jaw is shortened. Originally, AMC was mapped
      to a 5 Mb region on pig chromosome 5 (SSC5) between microsatellite markers SW152
      and SW904. In order to detect unaffected carriers a diagnostic test using markers
      within the candidate region was developed. However, two independent recombination
      events occurred in a diseased and in a healthy piglet. Therefore, we selected 24
      consecutive markers (3 microsatellites, 19 SNPs and 2 indels) in the candidate
      region, and determined the haplotypes in the two pedigrees with the
      recombinations. The parents and five offspring were investigated. In consequence,
      we were able to narrow down the candidate region and map AMC between SNPs
      ALGA0032767 and DRGA0006010 on SSC5 which span around 2.32 Mb. The candidate
      region shares homology to human chromosome 12. However, we are still lacking good
      candidate genes. A PCR-RFLP was developed and is used as an improved genetic test
      for AMC.

PMID- 22405935
TI  - Regional EEG alpha power, coherence, and behavioral symptomatology in autism
      spectrum disorder.
AB  - OBJECTIVE: Although distinct patterns of resting brain electrical activity (EEG)
      and functional connectivity are believed to distinguish individuals with autism
      spectrum disorders (ASD) from their unimpaired peers, researchers have only
      recently begun to link patterns of brain activity and connectivity to behavior in
      ASD. METHOD: We examined regional eyes-closed and eyes-open EEG alpha power and
      coherence at rest in relation to self-reported perceptual and social behavior in
      15 adults diagnosed with ASD and a matched comparison group of 16 unimpaired
      adults. RESULTS: The groups did not differ on eyes-closed EEG alpha power or
      coherence, but adults with ASD showed less alpha suppression for the eyes-open
      condition than did controls. In the ASD group, preferential attention to detail
      (perceptual domain) was associated with lower levels of alpha activity and
      reduced coherence in posterior regions. No relations between social interaction
      difficulties (social domain) and alpha measures were found for either group
      alone. CONCLUSIONS: These relations suggest that the processing of perceptual
      details may be carried out by relatively less synchronized neuronal units in
      adults with ASD, and may be relatively automatic. SIGNIFICANCE: Findings are
      discussed in relation to recent models of narrow minicolumnar brain structure and
      reduced functional neural connectivity in ASD.

PMID- 22405936
TI  - Mesocosm experiments to assess the transmission of Pandora neoaphidis within
      simple and mixed field margins and over the crop-margin interface.
AB  - Although considerable research on the development of agri-environment schemes has
      focussed on the value of managed field margins as reservoirs for arthropod
      natural enemies, their potential as reservoirs of entomopathogenic fungi has
      received less attention. Whether field margins that are most beneficial for
      arthropod natural enemies are the same as those for entomopathogenic fungi is
      unknown. Here, within glasshouse mesocosms, we assessed the reproductive success
      of the aphid-specific entomopathogenic fungus Pandora neoaphidis on aphids in a
      'simple margin' containing one plant species and on the same species of aphid in
      a 'mixed margin' containing seven plant species. These assessments were done in
      the presence of Aphidius ervi, a hymenopteran parasitoid of aphids regarded as
      being a key species to conserve in agri-environment schemes in the UK. When only
      the plants initially infested with aphids were assessed, transmission of P.
      neoaphidis was significantly greater (p<0.001) in the mixed margin as was
      parasitisation by A. ervi (p<0.05). However, when all of the plants in the
      mesocosms were assessed, transmission of P. neoaphidis remained greater in the
      mixed margin (p<0.05) whereas parasitisation by A. ervi was greater in the simple
      margin (p<0.05). This difference may be due to aphid dispersal which was greater
      in the simple margin thereby benefitting the actively foraging parasitoid whereas
      clustering of aphids in the mixed margin benefited the passively dispersed
      fungus. In a second mesocosm experiment, the movement of P. neoaphidis over the
      crop-margin interface was similar to that of A. ervi despite the fungus only
      being passively dispersed in contrast to the actively foraging parasitoid. The
      results presented here indicate that, although the optimal plant composition of
      field margins may differ for P. neoaphidis and A. ervi, both species can co-exist
      and reproduce in field margins and will move over the crop-margin interface.
      Managed field margins that benefit both key arthropod and key microbial enemies
      have potential for enhancing pest control in associated crops.

PMID- 22405937
TI  - Effect of temperature, photoperiod, flooding, and drying on the hatching pattern
      of the eggs of Strelkovimermis spiculatus (Nematoda: Mermithidae).
AB  - We assessed the number of Strelkovimermis spiculatus preparasites obtained from a
      known initial number of nematode eggs and the effect of abiotic conditions
      (temperature, photoperiod, flooding-drying) on the number of emerged
      preparasites. Two egg groups were maintained: one continuously flooded, another
      with flooding-drying cycles (every 15, 30, 60 days). Each egg group was studied
      at 25 degrees C and 14:10 (L:D) and 16 degrees C and 12:12 (L:D). The flooded
      eggs contained a higher overall percentage of S. spiculatus preparasites compared
      to the wet-dry-cycle eggs. The conditions of continuous flooding at 16 degrees C
      and 12:12 (L:D) produced the maximum percent of emerged J2s (30+/-15%).
      Preparasites were recorded by 7 (25 degrees C) and 14 (16 degrees C) days,
      suggesting this period as the minimum time for embryonic development. The
      preparasite-emergence time observed from the same flooded-egg batch (98 and 112
      days at 25 degrees C and 16 degrees C, respectively) suggested a nonsynchronous
      hatching, possibly through nonuniform egg embryonation. The time of exposure to
      drought in the assays did not significantly affect the total average percentage
      of J2s obtained at 25 degrees C and 14:10 (L:D), whereas at 16 degrees C the
      number of emerged J2s diminished with a prolongation of the drying period. The
      oviposition period was also recorded only at 16 degrees C and 12:12 (L:D): S.
      spiculatus eggs were detected at 12.6 days after postparasite emergence, and
      oviposition was complete at 51days under those conditions. We propose a flooding
      schedule to optimize the mass-rearing of S. spiculatus.

PMID- 22405938
TI  - Tenascin-C and its functions in neuronal plasticity.
AB  - The extracellular matrix glycoprotein tenascin-C (TN-C), a molecule highly
      conserved in vertebrates, is widely expressed in neural and non-neural tissue
      during development, repair processes in the adult organism, and tumorigenesis. In
      the developing central nervous system (CNS), in different brain regions TN-C is
      expressed in specific spatial and temporal patterns. In the adult CNS, its
      expression remains in areas of active neurogenesis and areas that exhibit
      neuronal plasticity. Understanding of the contribution of this extracellular
      matrix constituent to the major developmental processes such as cell
      proliferation and migration, axonal guidance, as well as synaptic plasticity, is
      derived from studies on TN-C deficient mice. Studies on these mice demonstrated
      that TN-C plays an important role in neuronal plasticity in the cerebral cortex,
      hippocampus and cerebellum, possibly by modulating the activity of L-type voltage
      dependent Ca(2+) channels.

PMID- 22405939
TI  - Cytotoxic and genotoxic effects of high-frequency electromagnetic fields (GSM
      1800 MHz) on immature and mature rats.
AB  - We investigated the cytogenotoxic effects of high frequency electromagnetic
      fields (HF-EMF) for 45 day and the effect of a recovery period of 15 day after
      exposure to EMF on bone marrow cells of immature and mature rats. The animals in
      treatment groups were exposed to 1800 MHz EMF at SAR of 0.37 W/kg and 0.49 W/kg
      for 2h/day for 45 day. Two recovery groups were kept for a recovery period of 15
      day without EMF after exposure to HF-EMF. Two control groups for both immature
      and mature rats were also included. Significant differences were also observed in
      chromosome aberrations (CA), micronucleus (MN) frequency, mitotic index (MI) and
      ratio of polychromatic erythrocytes (PCEs) in all treatment groups. The
      cytogenotoxic damage was more remarkable in immature rats and, the recovery
      period did not improve this damage in immature rats. Because much higher and
      irreversible cytogenotoxic damage was observed in immature rats than in mature
      rats, further studies are needed to understand effects of EMF on DNA damage and
      DNA repair, and to determine safe limits for environment and human, especially
      for children.

PMID- 22405940
TI  - Direct interaction with no correlation: an experimental pitfall in neural
      systems.
AB  - Neural systems continuously optimize how organisms process their environment and
      are highly dynamic. Building predictive models of these systems is challenging
      due to the large number of their elements. Therefore, in experimental and
      descriptive neurobiology the researcher typically does not seek to catalogue all
      variables that affect one another, but rather tries to isolate variables that
      interact directly. Because of methodological limitations, observed variables are
      often measured near equilibrium. The presented analysis demonstrates that
      statistical tests performed on such equilibrium values are fundamentally
      incapable of detecting direct interactions in a large subset of simple dynamical
      systems. Some of these problems can be avoided by using explicit statistical
      models that include time as a variable.

PMID- 22405941
TI  - The triple compression stress test for diagnosis of tarsal tunnel syndrome.
AB  - BACKGROUND: The diagnosis of tarsal tunnel syndrome (TTS) lacks objectivity and
      consistency. METHODOLOGY: A new test was designed, called triple compression
      stress test (TCST), to elicit stress on posterior tibial nerve and its branches,
      in an attempt to provoke signs of its entrapment. In this test, the ankle is
      placed in full planter flexion and the foot in inversion, with even, constant
      digital pressure applied over the posterior tibial nerve. Basic clinical
      examination to fifty patients with symptoms suggestive of TTS in one or both feet
      was done. Forty healthy volunteers (80 feet) were enrolled as a control group in
      the study. We then performed our designed clinical TCST, as well as, basic
      conventional electrodiagnostic studies bilaterally on all patients and controls.
      Consecutively, electrodiagnostic TCST was done for patients with negative basic
      nerve conduction results. RESULTS: The clinical TCST was positive in 61 out of 65
      (93.8%) symptomatic feet. It provoked symptoms in 6 new asymptomatic feet. The
      electrodiagnostic TCST was positive in 78 feet, of which 67 had a positive
      clinical test and 11 had false negative clinical test. Both tests were negative
      in all the control feet. Clinical TCST sensitivity was 85.9% while specificity
      was 100%. CONCLUSION: TCST achieved a simple, fast and very reliable provocative
      maneuver to increase the sensitivity of TTS diagnosis both clinically and
      electrophysiologically.

PMID- 22405942
TI  - Protein biomarkers for in vitro testing of toxicology.
AB  - The vision of the toxicology in the 21st century movement is to overcome the
      currently used animal tests and identify molecular pathways of toxicity, using
      human in vitro systems with the aim to provide the most relevant mechanistic
      information for human risk assessment. It is expected to translate key surrogate
      biomarkers to novel types of toxicity-related high throughput screening of the
      many thousands of compounds which need to be tested during development phases of
      the pharmaceutical industry and with regard to the REACH legislation in Europe.
      Systems biology, an emerging and increasingly popular field of research, appears
      to be the discipline of choice to integrate results from transcriptomics,
      proteomics, epigenomics and metabonomics technologies used to analyze samples
      from toxicological models. The challenges, however, with respect to data
      generation, statistical treatment, bioinformatic integration and interpretation
      or in silico modeling remain formidable. One of the main difficulties is the fact
      that the sheer number of molecular species is inflated enormously in the course
      of translation from genes to proteins due to post-translational modifications.
      Moreover, at the level of proteins, time scales of cellular reactions to toxic
      insults can be very fast, ranging from milliseconds to seconds. Linear dynamic
      ranges of concentration differences between conditions can also differ by several
      orders of magnitude. So, the search for protein biomarkers of toxicity requires
      sophisticated strategies for time-resolved quantitative differential approaches.
      The statistical principles, normalization of primary data and principal component
      and cluster analysis have been well developed for genomics/transcriptomics and
      partly for proteomics, but have not been widely adapted to technologies like
      metabonomics. Also, the integration of functional data, in particular data from
      mass spectrometry, with the aim of modeling pathways of toxicity for human risk
      assessment, is still at an infant stage.

PMID- 22405943
TI  - A new mechanism to ensure integration during LINE retrotransposition: a
      suggestion from analyses of the 5' extra nucleotides.
AB  - Long interspersed elements (LINEs) are transposable elements that exist in the
      chromosomal DNA of most eukaryotes; as such, they have a large impact on the
      genome evolution of their hosts. LINEs mobilize by a mechanism called
      retrotransposition in which the LINE RNA is reverse-transcribed into DNA and then
      integrated into the host chromosome. The integration of the 3' end of the LINE
      element simultaneously occurs with the initiation of reverse transcription; this
      process is called target-primed reverse transcription and is one of the important
      characteristics of LINEs. However, the molecular mechanism of the integration of
      the 5' end is not well understood. Here, we show that, in cultured cells, the
      integrants of the zebrafish ZfL2-2 LINE produce extra nucleotides at their 5'
      ends, and the extra nucleotides originate from their flanking sequences. We also
      found that, in cultured cells, some integrants of the human L1 LINE and, in their
      native hosts, some endogenous elements of two other LINEs also contain 5' extra
      nucleotides of similar origin, suggesting that the mechanism for generation of
      the 5' extra nucleotides is universal among various LINEs. From these data, we
      propose a general mechanism for 5' integration in LINE retrotransposition.

PMID- 22405944
TI  - Low dependency of retrotransposition on the ORF1 protein of the zebrafish LINE,
      ZfL2-1.
AB  - The zebrafish long interspersed element (LINE), ZfL2-1, which belongs to the L2
      clade, contains two open reading frames, ORF1 and ORF2. ORF1 encodes a protein
      containing a coiled-coil motif and an esterase domain, whereas ORF2 encodes a
      protein containing an endonuclease and a reverse transcriptase domain. To
      elucidate the functional significance of ORF1 in retrotransposition, we
      constructed many variants of ZfL2-1 and examined their retrotransposition
      ability. We concluded: 1) the ORF1 protein is not essential for ZfL2-1
      retrotransposition in cultured cells; 2) the translation of ORF1 is required for
      the translation of ORF2; and 3) ORF2 translation probably occurs via suppression
      of the ORF1 stop codon, the efficiency of which is influenced by the context of
      the sequence juxtaposed to the 3' side of the stop codon. These results offer a
      new perspective on the evolution of the L2 clade LINEs.

PMID- 22405945
TI  - Prevalence of Clostridium botulinum and thermophilic heat-resistant spores in raw
      carrots and green beans used in French canning industry.
AB  - Two categories of vegetables (carrots and green beans) that are widely used in
      the manufacture of canned food were surveyed for their spore contamination.
      Samples were recovered from 10 manufactures spread over all producing areas in
      France. Two samples over 316 raw vegetables collected were found positive for
      botulinum neurotoxin producing Clostridia spores as tested by PCR-based GeneDisc
      assay. Both positive samplestested positive for the type B neurotoxin gene
      (bont/B). In parallel, heat-resistant spores of thermophilic bacteria that are
      likely to be associated with canned food spoilage after prolonged incubation at
      55  degrees C were surveyed after specific enrichment. Prevalence varied between
      1.6% for Moorella thermoacetica/thermoautotrophica in green bean samples and 8.6%
      for either Geobacillus stearothermophilus or Thermoanaerobacterium spp. in carrot
      samples. Vegetable preparation, e.g. washing and edge cutting, considerably
      reduced spore contamination levels. These data constitute the first wide
      examination of vegetables specifically cultivated for industrialpurposes for
      their contamination by spores of thermophilic bacterial species.

PMID- 22405946
TI  - Shiga toxigenic Escherichia coli show strain dependent reductions under dry
      fermented sausage production and post-processing conditions.
AB  - Dry-fermented sausages (DFS) are considered possible risk products regarding
      Shiga toxigenic Escherichia coli (STEC). We have compared the reduction of 11 E.
      coli isolates of various serogroups in salami during the sausage production
      process and during post-process measures including storage, heating and freezing.
      The 11 E. coli isolates, mainly STEC, included enterohaemorrhagic E. coli (EHEC)
      outbreak strains linked to DFS along with apathogenic E. coli. During sausage
      production, there was a statistically significant difference in reduction between
      the E. coli strains ranging from 1.3 to 2.4 log10 (p<0.001). When sausages were
      subjected to post-process heat treatment of 43  degrees C for 24 h, a total
      reduction of more than 5 log10 was obtained for all E. coli isolates. Freezing
      and thawing of DFS with subsequent storage for 1 month at 16 or 20  degrees C
      generally contributed to large E. coli reductions with the latter conditions
      giving an average additional 3.9 log10 reduction, with a range from 3.4 to 4.4
      log10. The combination of freezing and 1 month of storage gave higher reductions
      compared with storage for 2 months for all examined temperatures. No systematic
      differences in survival of E. coli of different serogroups were detected for the
      different post-process measures. The reductions were also similar to those of
      apathogenic control isolates. Isolates showing higher survival during the
      ripening process did not have a lower reduction when exposed to post-process
      stress like storage, heating and freezing. The ability of the isolates to survive
      in salami was also compared with their survival at equivalent conditions in a
      tryptic soy broth (TSB) model. There was a low and not significant correlation
      (p>0.1) between the reductions of E. coli in salami and in the TSB broth model.
      Results based on broth models and/or single or surrogate strains must therefore
      be interpreted with caution. The EHEC reducing post-processing measures tested
      can easily be implemented in DFS production with marginal influence on the
      quality of the sausages.

PMID- 22405947
TI  - Circulation of genotype 4 hepatitis E virus in Europe: first autochthonous
      hepatitis E infection in France.
AB  - BACKGROUND: Human HEV infections reported in Europe without previous travel to
      endemic regions are linked to exposure to genotype 3 Hepatitis E virus
      (HEV).Genotype 3 is widely distributed through human cases and zoonotic
      reservoir. The geographical distribution of genotype 4 is limited to Asian
      countries. OBJECTIVES: The first human case of autochthonous genotype 4 hepatitis
      E infection was reported in France. STUDY DESIGN: The HEV infection was described
      in an immunosuppressed patient, presenting an acute myeloblastic leukemia.
      Investigation of the case was performed on detection of HEV markers in the
      patient and in the environment. RESULTS: Hepatitis E infection was diagnosed on
      the basis of HEV RNA viremia, and detection of anti-HEV IgM. The prognostic of
      leukemia was favorable and HEV was cleared without relapsing. HEV isolate was
      classified into genotype 4. CONCLUSIONS: The recent characterization of genotype
      4 HEV through swine surveillance in Europe and the description of the first human
      case in France open interesting questions about the circulation of this genotype:
      health risks in human population, transmission patterns, and zoonotic reservoir.

PMID- 22405948
TI  - Accidental epidural administration of Syntocinon.

PMID- 22405949
TI  - Microsurgical arterialization of degloving injuries of the upper limb.
AB  - The authors describe a technique in which a microsurgical anastomosis between an
      artery and a vein in an afferent direction (through a vein graft, when necessary)
      of a degloved flap is used to revascularize or arterialize the flap. In 3
      difficult cases, there was substantial salvage of flap tissue.

PMID- 22405950
TI  - Ulnar variance: its relationship to ulnar foveal morphology and forearm
      kinematics.
AB  - PURPOSE: It is unclear how individual differences in the anatomy of the distal
      ulna affect kinematics and pathology of the distal radioulnar joint. This study
      evaluated how ulnar variance relates to ulnar foveal morphology and the
      pronosupination axis of the forearm. METHODS: We performed 3-dimensional computed
      tomography studies in vivo on 28 forearms in maximum supination and pronation to
      determine the anatomical center of the ulnar distal pole and the forearm
      pronosupination axis. We calculated the forearm pronosupination axis using a
      markerless bone registration technique, which determined the pronosupination
      center as the point where the axis emerges on the distal ulnar surface. We
      measured the depth of the anatomical center and classified it into 2 types:
      concave, with a depth of 0.8 mm or more, and flat, with a depth less than 0.8 mm.
      We examined whether ulnar variance correlated with foveal type and the distance
      between anatomical and pronosupination centers. RESULTS: A total of 18 cases had
      a concave-type fovea surrounded by the C-shaped articular facet of the distal
      pole, and 10 had a flat-type fovea with a flat surface without evident central
      depression. Ulnar variance of the flat type was 3.5 +/- 1.2 mm, which was
      significantly greater than the 1.2 +/- 1.1 mm of the concave type. Ulnar variance
      positively correlated with distance between the anatomical and pronosupination
      centers. CONCLUSIONS: Flat-type ulnar heads have a significantly greater ulnar
      variance than concave types. The pronosupination axis passes through the ulnar
      head more medially and farther from the anatomical center with increasing ulnar
      variance. CLINICAL RELEVANCE: This study suggests that ulnar variance is related
      in part to foveal morphology and pronosupination axis. This information provides
      a starting point for future studies investigating how foveal morphology relates
      to distal ulnar problems.

PMID- 22405951
TI  - [Capillary-cavernous hemangioma of the nasal septum].
AB  - INTRODUCTION: Hemangioma are rare benign vascular tumors. Histologically, there
      are several types including capillary, cavernous and mixed hemangioma. We present
      a very rare mixed hemangioma of the nasal septum. CASE REPORT: A 30-year-old
      woman consulted for unilateral epistaxis and nasal obstruction. CT scan revealed
      a tumor filling the rhinopharynx, strongly enhanced after injection of contrast
      medium. It was pedicled on the posterior and superior nasal septum. Arteriography
      revealed a vascular blush. Tumor exeresis was performed by paralateronasal
      approach and endoscopic surgery. The histological examination identified a mixed
      hemangioma. DISCUSSION: Capillary and cavernous hemangiomas are rare and benign
      vascular tumors developing in the skin and subcutaneous tissues of the head and
      neck, and/or oral and nasal mucosa. No mixed hemangioma exclusively involving the
      nasal septum had been previously reported. Complete surgical resection is the
      treatment of choice, providing a favorable prognosis with low risk of recurrence.

PMID- 22405952
TI  - [Zygomatic bone repositioning osteotomies].
AB  - INTRODUCTION: The main morphological sequels of zygomatic bone fractures are lack
      of zygomatic projection and enopthalmia. They may be corrected by zygomatic
      osteotomy which is a difficult operation because of modified anatomic landmarks.
      Onlay bone or alloplastic grafts are preferred. TECHNICAL NOTE: Zygomatic
      osteotomies are performed through three surgical approaches: superior palpebral,
      sub-ciliary, and upper vestibular, followed by repositioning with osteosynthesis
      micro-plates. They allow reconstruction with an adequate projection in three
      dimensions. Surgery is usually associated with a bone graft of the orbital floor.
      DISCUSSION: Zygomatic osteotomy is a simple, reproducible technique, but it
      requires a good bone exposure. The esthetic results are satisfactory with an
      uneventful outcome. This surgical procedure is a good alternative to isolated
      techniques of autologous bone grafting or alloplastic material reconstruction
      which have sometimes disappointing and short lasting results due to graft
      resorption.

PMID- 22405953
TI  - Integrated PET/CT in non small cell lung cancer staging--clinical and
      pathological agreement.
AB  - INTRODUCTION: Integrated PET/CT has become a fundamental tool in the preoperative
      assessment of non small lung cancer (NSCLC) providing useful anatomical and
      metabolic information to characterize tumoral lesions and to detect unsuspected
      metastatic disease. AIM: To compare the agreement between clinical and
      pathological staging before and after the use of PET/CT. MATERIAL AND METHODS:
      Retrospective study of patients with NSCLC who underwent potentially curative
      surgery throughout 10.5 years. Cohen's kappa coefficient was used to evaluate
      staging agreement. RESULTS: One hundred and fifty patients were evaluated, 78%
      males, with a mean age of 65 (+/-9.6) years. Thirteen percent were submitted to
      neoadjuvant chemotherapy. PET/CT was performed in 41%. Global agreement between
      clinical and pathological staging was 51% (kappa=0.3639). There was a
      statistically significant difference between the staging results in patients who
      underwent PET/CT, when compared to the subgroup who did not (p=0.003). For those
      with PET/CT false negatives occurred in less 39%, false positives in more 12% and
      clinical and pathological staging coincided in more 27%. The overall results
      reflected an improvement in the agreement between clinical and pathological
      staging in the PET/CT subgroup (67%, kappa=0.5737 vs 40%, kappa=0.2292). PET/CT
      accuracy was enhanced when patients re-staged after neoadjuvant therapy were
      excluded and a substantial staging agreement was obtained for those who had the
      exam only for staging purposes (73%, kappa=0.6323). CONCLUSION: Inclusion of
      PET/CT in NSCLC preoperative assessment improved the accuracy of the clinical
      staging, with a good level of agreement with pathological staging.

PMID- 22405954
TI  - Crohn's disease and intestinal tuberculosis: a clinical challenge.

PMID- 22405955
TI  - Feasibility and test-retest reliability of an electroencephalography-based brain
      mapping system in children with cerebral palsy: a preliminary investigation.
AB  - OBJECTIVE: To investigate the feasibility and test-retest reliability of a novel
      electroencephalography (EEG)-based brain mapping system in healthy children and
      children with cerebral palsy (CP). DESIGN: Correlation statistics. SETTING:
      University brain mapping and neurorehabilitation laboratory. PARTICIPANTS: A
      convenience sample of children (N=12; 5 healthy children, mean +/- SD, 12.6+/
      0.89y; 7 children with CP, mean +/- SD, 9.71+/-1.1y) participated in the study.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Mu band (8-12Hz) power
      values in event-related spectral perturbation maps during reach and grasp hand
      movements were repeatedly measured on 2 separate occasions (2h apart). Intraclass
      correlation coefficient (ICC(1,2)) tests were computed to determine test-retest
      reliability at the standard level of significance (P<.004). In addition, the
      feasibility of the system was determined by evaluating potential differences in
      the cortical activation areas obtained from topographical maps during actual
      reach and grasp motor tasks between healthy children and children with CP.
      RESULTS: The test-retest reliability results showed excellent reliability between
      the repeated measures, ranging from .93 (P=.000) to .99 (P=.000). Our EEG brain
      mapping system was capable of distinguishing differences in the cortical activity
      power (mu band power spectra) between healthy children and children with CP.
      CONCLUSIONS: To our knowledge, this study is the first evidence demonstrating the
      feasibility and reliability of the EEG brain mapping system. Clinically, this
      system provides important insights into neuroplasticity associated with motor
      recovery after treatment and can also be used as real-time neurofeedback or
      noninvasive neuromodulation in the course of neurologic rehabilitation.

PMID- 22405956
TI  - Precise measurement and calculation of coincidence summing corrections for point
      and linear sources.
AB  - Point sources of (60)Co, (133)Ba, (134)Cs and (152)Eu, calibrated at Physikalisch
      Technische Bundesanstalt were measured in 13 positions on the axis of a 50%
      relative efficiency p-type detector. The peak and total efficiencies were
      calibrated using single photon emitting nuclides. Precise experimental values of
      the coincidence summing corrections were evaluated in each geometry. Synthetic
      linear source data, as well as the corresponding peak and total efficiency
      curves, were prepared using the dependence of the count rates on the position of
      the emitting point. The coincidence summing corrections for the linear sources
      were computed, analyzed with respect to different approximations and compared
      with simulations carried out with GESPECOR.

PMID- 22405957
TI  - Portable alpha spectrometer.
AB  - Many portable devices have been designed to detect gamma-rays or alpha and beta
      particles. Most of the alpha-particle detectors give the total count as a result,
      without identifying the radionuclides existing in the sample. The development of
      a device allowing rapid and straightforward alpha-particle spectrometry would be
      very useful for detecting the radioactive contents of unknown samples. This work
      describes the construction of a portable device using silicon semiconductor
      detectors designed to rapidly detect and possibly identify alpha-emitting
      radionuclides.

PMID- 22405958
TI  - Overview of a FPGA-based nuclear instrumentation dedicated to primary activity
      measurements.
AB  - In National Metrology Institutes like LNE-LNHB, renewal and improvement of the
      instrumentation is an important task. Nowadays, the current trend is to adopt
      digital boards, which present numerous advantages over the standard electronics.
      The feasibility of an on-line fulfillment of nuclear-instrumentation
      functionalities using a commercial FPGA-based (Field-Programmable Gate Array)
      board has been validated in the case of TDCR primary measurements (Triple to
      Double Coincidence Ratio method based on liquid scintillation). The new
      applications presented in this paper have been included to allow either an on
      line processing of the information or a raw-data acquisition for an off-line
      treatment. Developed as a complementary tool for TDCR counting, a time-to-digital
      converter specifically designed for this technique has been added. In addition,
      the description is given of a spectrometry channel based on the connection
      between conventional shaping amplifiers and the analog-to-digital converter (ADC)
      input available on the same digital board. First results are presented in the
      case of alpha- and gamma-counting related to, respectively, the defined solid
      angle and well-type NaI(Tl) primary activity techniques. The combination of two
      different channels (liquid scintillation and gamma-spectrometry) implementing the
      live-time anticoincidence processing is also described for the application of the
      4pibeta-gamma coincidence method. The need for an optimized coupling between the
      analog chain and the ADC stage is emphasized. The straight processing of the
      signals delivered by the preamplifier connected to a HPGe detector is also
      presented along with the first development of digital filtering.

PMID- 22405959
TI  - The coincidence-summing correction of the Compton-suppression spectrometer.
AB  - The compton-suppression Spectrometer can suppress the Compton baseline and make
      weak full energy peaks prominent in low-level activity gamma spectra, so it is
      used to measure environmental radioactive samples. In order to quantify the
      activities of the radionuclides in the sample coincidence-summing corrections
      should be applied. In this article the expressions of coincidence-summing
      correction of Compton-Suppression Spectrometer were deduced and the validity of
      the expressions was verified.

PMID- 22405960
TI  - The effect of music on corticospinal excitability is related to the perceived
      emotion: a transcranial magnetic stimulation study.
AB  - Transcranial magnetic stimulation (TMS) and neuroimaging studies suggest a
      functional link between the emotion-related brain areas and the motor system. It
      is not well understood, however, whether the motor cortex activity is modulated
      by specific emotions experienced during music listening. In 23 healthy
      volunteers, we recorded the motor evoked potentials (MEP) following TMS to
      investigate the corticospinal excitability while subjects listened to music
      pieces evoking different emotions (happiness, sadness, fear, and displeasure), an
      emotionally neutral piece, and a control stimulus (musical scale). Quality and
      intensity of emotions were previously rated in an additional group of 30 healthy
      subjects. Fear-related music significantly increased the MEP size compared to the
      neutral piece and the control stimulus. This effect was not seen with music
      inducing other emotional experiences and was not related to changes in autonomic
      variables (respiration rate, heart rate). Current data indicate that also in a
      musical context, the excitability of the corticomotoneuronal system is related to
      the emotion expressed by the listened piece.

PMID- 22405961
TI  - Losing the sound of concepts: damage to auditory association cortex impairs the
      processing of sound-related concepts.
AB  - Conceptual knowledge is classically supposed to be abstract and represented in an
      amodal unitary system, distinct from the sensory and motor brain systems. A more
      recent embodiment view of conceptual knowledge, however, proposes that concepts
      are grounded in distributed modality-specific brain areas which typically process
      sensory or action-related object information. Recent neuroimaging evidence
      suggested the significance of left auditory association cortex encompassing
      posterior superior and middle temporal gyrus in coding conceptual sound features
      of everyday objects. However, a causal role of this region in processing
      conceptual sound information has yet to be established. Here we had the unique
      chance to investigate a patient, JR, with a focal lesion in left posterior
      superior and middle temporal gyrus. To test the necessity of this region in
      conceptual and perceptual processing of sound information we administered four
      different experimental tasks to JR: Visual word recognition, category fluency,
      sound recognition and voice classification. Compared with a matched control
      group, patient JR was consistently impaired in conceptual processing of sound
      related everyday objects (e.g., "bell"), while performance for non-sound-related
      everyday objects (e.g., "armchair"), animals, whether they typically produce
      sounds (e.g., "frog") or not (e.g., "tortoise"), and musical instruments (e.g.,
      "guitar") was intact. An analogous deficit pattern in JR was also obtained for
      perceptual recognition of the corresponding sounds. Hence, damage to left
      auditory association cortex specifically impairs perceptual and conceptual
      processing of sounds from everyday objects. In support of modality-specific
      theories, these findings strongly evidence the necessity of auditory association
      cortex in coding sound-related conceptual information.

PMID- 22405962
TI  - Disturbed myocardial connexin 43 and N-cadherin expressions in hypoplastic left
      heart syndrome and borderline left ventricle.
AB  - OBJECTIVES: Borderline left ventricle is the left ventricular morphology at the
      favorable end of the hypoplastic left heart syndrome. In contrast to the severe
      end, it is suitable for biventricular repair. Wondering whether it is possible to
      identify cases suitable for biventricular repair from a developmental viewpoint,
      we investigated the myocardial histology of borderline and severely hypoplastic
      left ventricles. METHODS: Postmortem specimens of neonatal, unoperated human
      hearts with severe hypoplastic left heart syndrome and borderline left ventricle
      were compared with normal specimens and hearts from patients with transposition
      of the great arteries. After tissue sampling of the lateral walls of both
      ventricles, immunohistochemical and immunofluorescence stainings against cardiac
      troponin I, N-cadherin, and connexin 43, important for proper cardiac
      differentiation, were done. RESULTS: All severely hypoplastic left hearts (7/7)
      and most borderline left ventricle hearts (4/6) showed reduced sarcomeric
      expressions of troponin I in left and right ventricles. N-cadherin and connexin
      43 expressions were reduced in intercalated disks. The remaining borderline left
      ventricle hearts (2/6) were histologically closer to control hearts. CONCLUSIONS:
      Four of 6 borderline left ventricle hearts showed myocardial histopathology
      similar to the severely hypoplastic left hearts. The remainder were similar to
      normal hearts. Our results and knowledge regarding the role of epicardial-derived
      cells in myocardial differentiation lead us to postulate that an abnormal
      epicardial-myocardial interaction could explain the observed histopathology.
      Defining the histopathologic severity with preoperative myocardial biopsy samples
      of hearts with borderline left ventricle might provide a diagnostic tool for
      preoperative decision making.

PMID- 22405963
TI  - Residency training and use of strategies to promote community child health one
      year after graduation.
AB  - OBJECTIVE: Training pediatricians to understand child health in the context of
      community and to develop skills to engage with community organizations remain
      priorities for residency education in the United States. Our objectives were to:
      1) determine use of strategies to influence community child health by graduates
      of the Community Pediatrics Training Initiative (CPTI); and 2) to identify
      personal, practice, and residency program factors associated with use of
      strategies 1 year after residency. METHODS: Analysis of data from the Dyson
      Initiative National Evaluation included surveys of physicians ("graduates") 1
      year after residency and surveys of CPTI program leaders. Graduates reported
      personal and practice characteristics and use of one or more strategies to
      influence community child health. Chi-square and logistic regression were used to
      examine associations between personal, practice, and programmatic factors with
      use of strategies. RESULTS: Of the 511 graduates (68% participation), 44%
      reported use of one or more strategies. After adjusting for residency site, time
      spent in general pediatrics, and program emphasis on individual level advocacy,
      we found that graduates were more likely to report using strategies if they felt
      responsible for improving community child health (adjusted odds ratio [aOR] 4.1,
      95% confidence interval [95% CI] 2.5-6.9), had contact with a person who provides
      guidance about community pediatrics (aOR 1.8, CI 1.2-2.6), or trained in a
      program that places great emphasis on teaching population level advocacy skills
      (aOR 2.3, CI 1.3-4.2). CONCLUSIONS: Personal perspectives and residency education
      influence community involvement, even early in pediatricians' careers. Efforts
      are needed to understand how content and delivery of training influence community
      engagement over time.

PMID- 22405964
TI  - Median facial clefts in Xenopus laevis: roles of retinoic acid signaling and
      homeobox genes.
AB  - The upper lip and primary palate form an essential separation between the brain,
      nasal structures and the oral cavity. Surprisingly little is known about the
      development of these structures, despite the fact that abnormalities can result
      in various forms of orofacial clefts. We have uncovered that retinoic acid is a
      critical regulator of upper lip and primary palate development in Xenopus laevis.
      Retinoic acid synthesis enzyme, RALDH2, and retinoic acid receptor gamma
      (RARgamma) are expressed in complementary and partially overlapping regions of
      the orofacial prominences that fate mapping revealed contribute to the upper lip
      and primary palate. Decreased RALDH2 and RARgamma result in a median cleft in the
      upper lip and primary palate. To further understand how retinoic acid regulates
      upper lip and palate morphogenesis we searched for genes downregulated in
      response to RARgamma inhibition in orofacial tissue, and uncovered homeobox genes
      lhx8 and msx2. These genes are both expressed in overlapping domains with
      RARgamma, and together their loss of function also results in a median cleft in
      the upper lip and primary palate. Inhibition of RARgamma and decreased Lhx8/Msx2
      function result in decreased cell proliferation and failure of dorsal anterior
      cartilages to form. These results suggest a model whereby retinoic acid signaling
      regulates Lhx8 and Msx2, which together direct the tissue growth and
      differentiation necessary for the upper lip and primary palate morphogenesis.
      This work has the potential to better understand the complex nature of the upper
      lip and primary palate development which will lead to important insights into the
      etiology of human orofacial clefts.

PMID- 22405965
TI  - A novel method to enhance the efficiency of drug transdermal iontophoresis
      delivery by using complexes of drug and ion-exchange fibers.
AB  - The main reason for generally low efficiency of the transdermal iontophoretic
      drug delivery is that the fraction of the total current contributed by the drug
      ions is very small. The objective of this study was to find a method to increase
      the fraction of the total current contributed by the drug ions so as to enhance
      the drug's iontophoretic delivery. Iontophoretic transport of diclofenac solution
      and diclofenac assisted by ion exchange materials, including ion-exchange resin,
      ion-exchange membrane and ion-exchange fiber, across the rat skin were
      investigated. Both in vitro and in vivo iontophoretic transport experiments
      showed the amount of diclofenac permeated across rat skin from the diclofenac
      fibers was highest among those from the diclofenac simple solutions and ion
      exchange materials complexes. The results of this study suggested that there is
      an enhancement of drug across rat skin by ion-exchange fibers in ion-exchange
      fibers assisted iontophoresis. The present study has demonstrated the potential
      of a new approach using ion-exchange fibers to enhance transdermal iontophoretic
      transport of an ionizable drug.

PMID- 22405966
TI  - Incorporating Turbula mixers into a blending scale-up model for evaluating the
      effect of magnesium stearate on tablet tensile strength and bulk specific volume.
AB  - Turbula bottle blenders are often used in lab-scale experiments during early
      stage pharmaceutical product development. Unfortunately, applying knowledge
      gained with these blenders to larger-sized diffusion mixers is limited by the
      lack of blending models that include Turbula mixers. To address this need for
      lubrication blending scale-up, 2:1 blends of microcrystalline cellulose and spray
      dried lactose or dibasic calcium phosphate were mixed with 1% magnesium stearate
      using Turbula bottle blenders, varying bottle volume, V (30-1250mL); bottle
      headspace fraction, F(headspace) (30-70%); and the number of blending cycles, r
      (24 to ~190,000 cycles). The impact of lubrication blending on tensile strength
      and bulk specific volume quality attributes, QA, was modeled by:where QA(0) is
      initial QA value, beta is sensitivity of QA to lubrication, gamma is formulation
      specific lubrication rate constant, and L is characteristic mixing length scale
      (i.e. 1.5V(1/3) for Turbula blenders, V(1/3) for simple diffusion mixers). The
      factor of 1.5 captures the bottle dimensions and the more complex mixing dynamics
      of the Turbula blender. This lubrication blending process model is valid for
      scale-up from 30-mL to 200-L blenders. Assessing bulk specific volume may provide
      a simpler, more material-sparing means for determining gamma than tensile
      strength, since these QAs exhibited similar gamma values.

PMID- 22405967
TI  - Aminoalkyl methacrylate copolymers for improving the solubility of tacrolimus. I:
      Evaluation of solid dispersion formulations.
AB  - The aim of this study was to investigate the effect of Eudragit E/HCl (E-SD) on
      the reprecipitation of a poorly water-soluble drug, tacrolimus. To evaluate the
      inhibition of reprecipitation of E-SD, reprecipitation studies on tacrolimus were
      conducted using a dissolution test method. Solubility of tacrolimus was measured
      at regular intervals in a dissolution media, in which tacrolimus was dissolved in
      ethanol, and the test media contained additives for inhibiting precipitation.
      Supersaturation profiles of tacrolimus were observed, and were maintained for 24h
      only with E-SD. Solid dispersion formulations of tacrolimus prepared with
      hydroxypropylmethylcellulose (HPMC) or E-SD in different drug/carrier ratios were
      also investigated. Solid dispersions prepared with E-SD showed higher solubility
      of tacrolimus compared with that of HPMC. In the E-SD formulation, the drug
      solubility influences to drug/carrier ratio. The formulation of drug/E-SD (1/5)
      showed the highest drug solubility. Thus, it may be inferred that a definite
      drug/carrier ratio exists to increase drug solubility. Further, by mixing E-SD
      the solid dispersion prepared with HPMC showed enhanced drug solubility.

PMID- 22405969
TI  - Sudden cardiac death and tuberculosis - how much do we know?
AB  - Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a major killer in the
      world and pulmonary infections are well characterised. It is not widely known
      that TB myocarditis leads to sudden cardiac deaths (SCD), especially in young
      people. Unlike other causes of SCD, risk factors such as family history are
      absent and patients are asymptomatic. This makes risk stratification and
      interventions with implantable cardiac defibrillators extremely difficult. Only a
      few cases of TB myocarditis SCD have been reported since 1977 and all of which
      were diagnosed at autopsy. The majority of reports showed extensive TB
      infiltration of the myocardium with no systemic symptoms. Concurrent miliary or
      systemic TB was postulated to be the source of TB myocarditis. The mechanism of
      death has been hypothesized to be ventricular tachyarrhythmia. Pulmonary TB has
      also been reported to cause sudden death. However, ventricular arrhythmias have
      not been recorded, suggesting a different mechanism to TB myocarditis SCD, which
      centres upon cardiopulmonary collapse leading to bradycardia. Although anti
      tuberculous chemotherapy is efficacious in the treatment of TB myocarditis, there
      is no evidence to suggest that it is effective in the prevention of SCD. It
      remains to be seen whether better global control of TB disease burden will result
      in reductions in SCD. Furthermore, no experimental data exist on the link between
      TB myocarditis SCD and arrhythmias. We propose a unifying diagnostic system for
      TB myocarditis based on the current data and molecular techniques. This is likely
      to require updates as more evidence becomes available.

PMID- 22405968
TI  - p53 and MDM2 are involved in the regulation of osteocalcin gene expression.
AB  - Osteocalcin (OC) is a major noncollagenous bone matrix protein and an osteoblast
      marker whose expression is limited to mature osteoblasts during the late
      differentiation stage. In previous studies we have shown osteosarcomas to lose
      p53 function with a corresponding loss of osteocalcin gene expression.
      Introduction of wild type p53 resulted in re expression of the osteocalcin gene.
      Using gel shift and chromatin immunoprecipitation assays, we have identified a
      putative p53 binding site within the rat OC promoter region and observed an
      increase in OC promoter activity when p53 accumulates using a CAT assay. The p53
      inducible gene Mdm2 is a well-known downstream regulator of p53 levels. Our
      results showed a synergistic increase in the OC promoter activity when both p53
      and MDM2 were transiently overexpressed. We further demonstrate that p53 is not
      degraded during overexpression of MDM2 protein. Increased OC expression was
      observed with concomitantly increased p53, VDR, and MDM2 levels in ROS17/2.8
      cells during treatment with differentiation promoting (DP) media, but was
      significantly decreased when co-treated with DP media and the small molecule
      inhibitor of MDM2-p53 interaction, Nutlin-3. We have also observed a dramatic
      increase of the OC promoter activity in the presence of p53 and Mdm2 with
      inclusion of Cbfa-1 and p300 factors. Our results suggest that under some
      physiological conditions the oncoprotein MDM2 may cooperate with p53 to regulate
      the osteocalcin gene during osteoblastic differentiation.

PMID- 22405970
TI  - The Rare Diseases Clinical Research Network Contact Registry update: features and
      functionality.
AB  - The Rare Diseases Clinical Research Network (RDCRN) Contact Registry has grown in
      size and scope since it was first reported in this journal in 2007. In this
      paper, we reflect on our seven years' experience developing and expanding the
      RDCRN Contact Registry to include many more rare diseases. We present the
      functional and data requirements that motivated this registry, and the new
      features and policies that have been developed since. Given the high costs and
      long-term commitment required to build patient registries, the RDCRN Contact
      Registry experience represents a reasonable approach for identifying and
      cultivating potential research populations, with minimal resources and patient
      burden. The basic model of a patient-reported registry has not changed since our
      2007 report, but the number of diseases has grown from 42 to 201, and the types
      of information that are exchanged with participants has expanded. A patient
      directed information-sharing feature has been added to reduce barriers to
      communication between investigators and patients affected by rare and genetic
      diseases. As specific data and research needs arise, the Contact Registry can be
      leveraged to access needed data or to solicit patients for particular research
      opportunities. This multiple-disease registry is scalable, expandable, and
      standards-driven, and has become a model for clinical and translational research
      across rare and many other diseases.

PMID- 22405971
TI  - The views of patients and healthy volunteers on participation in clinical trials:
      an exploratory survey study.
AB  - BACKGROUND AND AIMS: This study was conducted to investigate the views of
      patients and healthy volunteers on participation in clinical trials. METHODS: A
      total of 291 clinical trial participants, including 140 patients and 151 healthy
      volunteers, were recruited from four university hospital-affiliated clinical
      trial centers among 15 Korean regional clinical trial centers in South Korea
      where the levels of information and care were sufficient to meet the global
      standard. Participants were recruited from phase I trials or bioequivalence
      tests, a short term hospitalization under close monitoring in the clinical trial
      centers, or from phase II, III or IV trials occurring in both wards and
      outpatient clinics. A structured questionnaire survey was performed to identify
      their perspectives on clinical trials. RESULTS: Participants who were patients
      were significantly influenced by medical personnels regarding the decision making
      processes for participation in clinical trials when compared to healthy
      volunteers. However, no difference was found between the two groups in the level
      of willingness to participate in and satisfaction with clinical trials. More than
      50% of patient subjects misunderstood and thought that their physicians could
      persuade them to participate in clinical trials or that all the participants
      would receive a new drug or treatment during trials. CONCLUSIONS: Clinical
      researchers who are involved in clinical trials should make an extra effort to
      confirm the level of understanding of their patients regarding the clinical trial
      and to guarantee that each patient has sufficient time to make an informed
      decision before participating in a clinical trial.

PMID- 22405972
TI  - Derivation of autism spectrum disorder-specific induced pluripotent stem cells
      from peripheral blood mononuclear cells.
AB  - Induced pluripotent stem cells (iPSCs) hold tremendous potential both as a
      biological tool to uncover the pathophysiology of disease by creating relevant
      cell models and as a source of stem cells for cell-based therapeutic
      applications. Typically, iPSCs have been derived by the transgenic overexpression
      of transcription factors associated with progenitor cell or stem cell function in
      fibroblasts derived from skin biopsies. However, the need for skin punch biopsies
      to derive fibroblasts for reprogramming can present a barrier to study
      participation among certain populations of individuals, including children with
      autism spectrum disorders (ASDs). In addition, the acquisition of skin punch
      biopsies in non-clinic settings presents a challenge. One potential mechanism to
      avoid these limitations would be the use of peripheral blood mononuclear cells
      (PBMCs) as the source of the cells for reprogramming. In this article we
      describe, for the first time, the derivation of iPSC lines from PBMCs isolated
      from the whole blood of autistic children, and their subsequent differentiation
      in GABAergic neurons.

PMID- 22405973
TI  - Superoxide flashes: elemental events of mitochondrial ROS signaling in the heart.
AB  - The role of mitochondrial reactive oxygen species (mitoROS) in cellular function
      remains obscure. By synthesizing recent data, we propose here that local dynamic
      mitoROS in the form of "superoxide flashes" serve as "signaling ROS" rather than
      "homeostatic ROS", distinguishable from basal mitoROS due to constitutive leakage
      of the electron transfer chain (ETC). Individual superoxide flashes are 10-s
      mitoROS bursts that are compartmentalized to a single mitochondrion or local
      mitochondrial networks. As a highly-conserved universal mitochondrial activity,
      it occurs in intact cells, in ex vivo beating hearts, and even in living animals.
      Unlike basal mitoROS, superoxide flashes are ignited by transient openings of a
      type of mitochondrial permeability transition pore (mPTP), and their incidence is
      richly regulated by an array of factors that converge on either the mPTP or ETC.
      Emerging evidence has shown that superoxide flashes decode dietary and metabolic
      status or exercise, gauge oxidative stress (e.g., during reoxygenation after
      hypoxia or anoxia), and constitute early mitochondrial signals that initiate
      oxidative stress-related apoptosis in a context-dependent manner. That they make
      only a miniscule contribution to global ROS attests to the high efficiency of
      local ROS signaling. However, the exact mechanisms underlying superoxide flash
      formation, regulation and function remain uncertain. Future investigation is
      warranted to uncover the cellular logic and molecular pathways of local dynamic
      mitoROS signaling in heart muscle cells and many other cell types.

PMID- 22405974
TI  - Evaluation of genotoxicity and oxidative damage in painters exposed to low levels
      of toluene.
AB  - Toluene is an organic solvent used in numerous processes and products, including
      industrial paints. Toluene neurotoxicity and reproductive toxicity are well
      recognized; however, its genotoxicity is still under discussion, and toluene is
      not classified as a carcinogenic solvent. Using the comet assay and the
      micronucleus test for detection of possible genotoxic effects of toluene, we
      monitored industrial painters from Rio Grande do Sul, Brazil. The putative
      involvement of oxidative stress in genetic damage and the influences of age,
      smoking, alcohol consumption, and exposure time were also assessed. Although all
      biomarkers of toluene exposure were below the biological exposure limits,
      painters presented significantly higher DNA damage (comet assay) than the control
      group; however, in the micronucleus assay, no significant difference was
      observed. Painters also showed alterations in hepatic enzymes and albumin levels,
      as well as oxidative damage, suggesting the involvement of oxidative stress.
      According to multiple linear regression analysis, blood toluene levels may
      account for the increased DNA damage in painters. In summary, this study showed
      that low levels of toluene exposure can cause genetic damage, and this is related
      to oxidative stress, age, and time of exposure.

PMID- 22405975
TI  - Re-evaluation of a reported increased micronucleus frequency in lymphocytes of
      workers occupationally exposed to formaldehyde.
AB  - A replicate evaluation of increased micronucleus (MN) frequencies in peripheral
      lymphocytes of workers occupationally exposed to formaldehyde (FA) was undertaken
      to verify the observed effect and to determine scoring variability. May-Grunwald
      Giemsa-stained slides were obtained from a previously performed cytokinesis-block
      micronucleus test (CBMNT) with 56 workers in anatomy and pathology laboratories
      and 85 controls. The first evaluation by one scorer (scorer 1) had led to a
      highly significant difference between workers and controls (3.96 vs 0.81 MN per
      1000 cells). The slides were coded before re-evaluation and the code was broken
      after the complete re-evaluation of the study. A total of 1000 binucleated cells
      (BNC) were analysed per subject and the frequency of MN (in 0/00) was determined.
      Slides were distributed equally and randomly between two scorers, so that the
      scorers had no knowledge of the exposure status. Scorer 2 (32 exposed, 36
      controls) measured increased MN frequencies in exposed workers (9.88 vs 6.81).
      Statistical analysis with the two-sample Wilcoxon test indicated that this
      difference was not significant (p=0.17). Scorer 3 (20 exposed, 46 controls)
      obtained a similar result, but slightly higher values for the comparison of
      exposed and controls (19.0 vs 12.89; p=0.089). Combining the results of the two
      scorers (13.38 vs 10.22), a significant difference between exposed and controls
      (p=0.028) was obtained when the stratified Wilcoxon test with the scorers as
      strata was applied. Interestingly, the re-evaluation of the slides led to clearly
      higher MN frequencies for exposed and controls compared with the first
      evaluation. Bland-Altman plots indicated that the agreement between the
      measurements of the different scorers was very poor, as shown by mean differences
      of 5.9 between scorer 1 and scorer 2 and 13.0 between scorer 1 and scorer 3.
      Calculation of the intra-class correlation coefficient (ICC) revealed that all
      scorer comparisons in this study were far from acceptable for the reliability of
      this assay. Possible implications for the use of the CBMNT in human biomonitoring
      studies are discussed.

PMID- 22405976
TI  - Analysis of in vitro chemoprevention of genotoxic damage by phytochemicals, as
      single agents or as combinations.
AB  - Cancer chemoprevention with low-dose combinations of bioactive phytochemicals
      instead of single agents has been suggested to induce less toxicity and improve
      efficacy. In this study, we selected four plant food-based phytochemicals, viz.
      chlorogenic acid (CLA), pelargonidin (PEL), resveratrol (RES) and
      epigallocatechin gallate (EGCG) to evaluate the in vitro chemoprevention of
      genotoxic damage in HL-60 cells. These agents were tested either individually or
      as a combination at two concentrations (with a 10-fold difference) against the
      genotoxins mitomycin C (MMC), diepoxybutane (DEB) and patulin (PAT). Our
      preliminary ferric reducing antioxidant power (FRAP) assay demonstrated additive
      effects when PEL, CLA, RES and EGCG were combined. Results of the cytokinesis
      block micronucleus test showed significant protection against genotoxic damage
      induced by PAT, DEB and MMC when CLA, PEL, RES and EGCG were tested individually.
      This protective effect of the phytochemicals was not concentration-related. Both
      low- and high-concentration combinations of CLA, PEL, RES and EGCG showed
      significant reducing effects on the frequencies of micronuclei induced by PAT,
      DEB and MMC. However, the micronucleus test did not provide indications of
      additive or synergistic effects with this combination of phytochemicals. In
      conclusion, the chemo-preventive effects of PEL, CLA, RES and EGCG against
      genotoxic damage induced by MMC, DEB and PAT are indicative of a 'saturation
      effect' when higher concentrations and combinations of these phytochemicals are
      used.

PMID- 22405977
TI  - Mentally challenged patients in a forensic hospital: a feasibility study
      concerning the executive functions of forensic patients with organic brain
      disorder, learning disability, or mental retardation.
AB  - The past years have seen an increasing number of patients of lower intelligence
      or with organic brain disorder being committed into our forensic psychiatry. Our
      clinic has an ongoing scientific project to investigate the possibilities of
      reducing costs while at the same time guaranteeing adequate treatment and
      enforcement practice in forensic hospitals. This current project did not take
      these kinds of patients into consideration initially. This feasibility study is
      intended to examine if and to what extent these patients can be part of the
      scientific project. All patients of forensic psychiatry in Rostock (Mecklenburg
      Western-Pomerania) with an IQ<80 (learning disorder) or a primary or secondary
      organic brain dysfunction that have been committed to the clinic since 2009 are
      included. These patients went through an extensive battery of neuropsychological
      tests. Furthermore, the treating psychotherapists had to rate the prognoses for
      criminal re-offending at discharge. Patients affected by lower intelligence or an
      organic brain dysfunction achieve lower results in neuropsychological testing
      than other patients participating in the main project. Nevertheless,
      participation in neuropsychological testing does not appear to overtax them.
      Future examination of the patients will be conducted to investigate to what
      extent certain therapeutic methods have been of noticeable benefit to this
      problematic group.

PMID- 22405978
TI  - Maternal anesthesia and fetal neurodevelopment.
AB  - It is clear from animal studies that commonly used anesthetic agents affect early
      brain development both histologically and functionally. With human epidemiologic
      evidence suggesting an association between anesthesia and surgery early in life
      and late-onset learning disabilities, investigators have focused their attention
      on the subtle long-term effects of anesthesia exposure. Most obstetric anesthesia
      studies, however, have focused on either the teratogenic effects of anesthetic
      agents in the first trimester or on the neonatal status immediately after
      delivery. Not much attention has been paid to the human second trimester, a
      period of active fetal brain development typified by neurogenesis and neuronal
      migration. Of concern though, is that these events are easily perturbed by
      environmental and pharmacological influences. New research studies have raised
      significant questions about the fetal impact of maternal anesthesia for non
      obstetric and fetal surgery. This review summarizes the major findings in the
      field of developmental neurotoxicity of anesthetic agents, discusses the
      susceptibility of the fetal brain to anesthetic effects in a trimester-specific
      style, and outlines the pitfalls in extrapolating animal research to humans.

PMID- 22405979
TI  - Successful resuscitation following amniotic fluid embolism in a patient
      undergoing induction of labour for late miscarriage.

PMID- 22405980
TI  - Management of an unusual major obstetric haemorrhage in a resource-poor setting.

PMID- 22405981
TI  - Prognostic importance of tobacco use in men receiving definitive prostate
      brachytherapy.
AB  - PURPOSE: Several prominent publications have identified an overall association
      between tobacco use and an increased risk of disease recurrence and disease
      specific mortality in prostate cancer patients. The authors explored whether
      tobacco use adversely impacts treatment outcomes in men treated with permanent
      interstitial brachytherapy. METHODS AND MATERIALS: From April 1995 to August
      2008, 2057 patients underwent brachytherapy by a single brachytherapist. Median
      follow-up was 7.5 years. The role of tobacco use as a prognostic factor for
      biochemical progression-free survival, cause-specific survival, and overall
      survival was investigated. Differences in survival between smokers and nonsmokers
      were compared using Kaplan-Meier curves and log-rank tests. RESULTS: Current
      smokers presented with a lower body mass index (p<0.001), smaller prostate size
      (p=0.003), younger age (p<0.001), higher prostate-specific antigen level
      (p=0.002), a trend toward higher percentage biopsy core involvement (p=0.08),
      higher incidence of perineural invasion (p=0.015), and higher risk disease
      (p<0.001) than former or nonsmokers. There was no difference in biochemical
      progression-free survival (p=0.30) or cause-specific survival (p=0.72) at 10
      years for smokers compared with nonsmokers. On univariate and multivariate
      analysis, tobacco use was an adverse risk factor for overall survival (p<0.001).
      There was no association between smoking and any prostate cancer-specific
      outcome. CONCLUSIONS: Smokers treated with brachytherapy have excellent outcomes
      and are at no higher risk of treatment failure than men who are nonsmokers.

PMID- 22405982
TI  - Use of cine phase-contrast MRI in the assessment of distal splenorenal shunt
      function.
AB  - Magnetic resonance imaging (MRI) features of a surgical splenorenal shunt in a 28
      year-old girl are described. The woman underwent color doppler ultrasonography
      during follow up for the shunt, which was inconclusive. MR was used to
      investigate the function of the shunt. Velocity and flow direction in splanchnic
      vessels and in the shunt were evaluated using cine fast phase-contrast sequences.
      MR findings could be of help in the evaluation of patients undergoing surgical
      shunts during follow up.

PMID- 22405983
TI  - Cardiac T2 measurements in patients with iron overload: a comparison of imaging
      parameters and analysis techniques.
AB  - Measurement of cardiac T2 has emerged as an important tool to noninvasively
      quantify cardiac iron concentration in order to detect preclinical evidence of
      toxic levels and titrate chelation therapy. However, there exists variation among
      practitioners in cardiac T2 measurement methods. This study examines the impact
      of different imaging parameters and data analysis techniques on the calculated
      cardiac R2 (1/T2) in patients at risk for cardiac siderosis. The study group
      consisted of 36 patients with thalassemia syndromes who had undergone clinical
      magnetic resonance imaging assessment of cardiac siderosis using a standardized
      protocol and who were selected to yield a broad range of cardiac R2 values.
      Cardiac R2 measurements were performed on a 1.5-T scanner using an
      electrocardiogram-gated, segmented, multiecho gradient echo sequence obtained in
      a single breath-hold. R2 was calculated from the signal intensity versus echo
      time data in the ventricular septum on a single midventricular short-axis slice.
      There was good agreement between R2 measured with a blood suppression prepulse
      (black blood technique) and without (mean difference 6.0 +/- 10.7 Hz). The black
      blood technique had superior within-study reproducibility (R2 mean difference 1.6
      +/- 8.6 Hz versus 2.7 +/- 14.6 Hz) and better interobserver agreement (R2 mean
      difference 3.4 +/- 8.2 Hz versus 8.3 +/- 16.5 Hz). With the same minimum echo
      time, the use of small (1.0 ms) versus large (2.2 ms) echo spacing had minimal
      impact on cardiac R2 (mean difference 0.3 +/- 8.7 Hz). The application of a
      region-of-interest-based versus a pixel-based data analysis also had little
      effect on cardiac R2 calculation (mean difference 8.4 +/- 6.9 Hz). With black
      blood images, fitting the signal curve to a monoexponential decay or to a
      monoexponential decay with a constant offset yielded similar R2 values (mean
      difference 3.4 +/- 8.1 Hz). In conclusion, the addition of a blood suppression
      prepulse for cardiac R2 measurement yields similar R2 values and improves
      reproducibility and interobserver agreement. The findings regarding other
      variations may be helpful in establishing a broadly accepted imaging and analysis
      technique for cardiac R2 calculation.

PMID- 22405984
TI  - Preoperative demonstration of neurovascular relationship in trigeminal neuralgia
      by using 3D FIESTA sequence.
AB  - PURPOSE: The purpose of the study was to evaluate the value of high-resolution
      three-dimensional fast imaging employing steady-state acquisition (3D FIESTA)
      imaging in the visualization of neurovascular relationship in patients with
      trigeminal neuralgia (TN). METHODS: Thirty-seven patients with unilateral typical
      TN underwent 3D FIESTA imaging. Neurovascular relationship at the trigeminal root
      entry zone was reviewed by an experienced neuroradiologist, who was blinded to
      the clinical details. The imaging results were compared with the operative
      findings in all patients. RESULTS: In 37 patients with TN, 3D FIESTA imaging
      identified surgically verified neurovascular contact in 35 of 36 symptomatic
      nerves. Based on surgical findings, the sensitivity and specificity of magnetic
      resonance (MR) imaging were 97.2% and 100%, respectively. Agreement between the
      position (medial, lateral, superior and inferior) of the compressing vessel
      relative to the trigeminal nerve identified by MR imaging and surgery was
      excellent (K=0.81; 95% confidence interval, 0.56-1.00). A statistically
      significant difference was found between the site of neurovascular contact and
      the clinical symptom related to the trigeminal branch (Fisher's Exact Test,
      P<.001). CONCLUSIONS: Use of 3D FIESTA sequence enables accurate visualization of
      neurovascular contact in patients with TN. Anatomic relationships defined by this
      method can be useful in surgical planning and predicting surgical findings.

PMID- 22405986
TI  - A novel mathematical model considering change of diffusion coefficient for
      predicting dissolution behavior of acetaminophen from wax matrix dosage form.
AB  - From wax matrix dosage forms, drug and water-soluble polymer are released into
      the external solvent over time. As a consequence, the pore volume inside the wax
      matrix particles is increased and the diffusion coefficient of the drug is
      altered. In the present study, we attempted to derive a novel empirical
      mathematical model, namely, a time-dependent diffusivity (TDD) model, that
      assumes the change in the drug's diffusion coefficient can be used to predict the
      drug release from spherical wax matrix particles. Wax matrix particles were
      prepared by using acetaminophen (APAP), a model drug; glyceryl monostearate (GM),
      a wax base; and aminoalkyl methacrylate copolymer E (AMCE), a functional polymer
      that dissolves below pH 5.0 and swells over pH 5.0. A three-factor, three-level
      (3(3)) Box-Behnken design was used to evaluate the effects of several of the
      variables in the model formulation, and the release of APAP from wax matrix
      particles was evaluated by the paddle method at pH 4.0 and pH 6.5. When comparing
      the goodness of fit to the experimental data between the proposed TDD model and
      the conventional pure diffusion model, a better correspondence was observed for
      the TDD model in all cases. Multiple regression analysis revealed that an
      increase in AMCE loading enhanced the diffusion coefficient with time, and that
      this increase also had a significant effect on drug release behavior.
      Furthermore, from the results of the multiple regression analysis, a formulation
      with desired drug release behavior was found to satisfy the criteria of the
      bitter taste masking of APAP without lowering the bioavailability. That is to
      say, the amount of APAP released remains below 15% for 10 min at pH 6.5 and
      exceeds 90% within 30 min at pH 4.0. The predicted formulation was 15% APAP
      loading, 8.25% AMCE loading, and 400 MUm mean particle diameter. When wax matrix
      dosage forms were prepared accordingly, the predicted drug release behavior
      agreed well with experimental values at each pH level. Therefore, the proposed
      model is feasible as a useful tool for predicting drug release behavior, as well
      as for designing the formulation of wax matrix dosage forms.

PMID- 22405987
TI  - Development and characterisation of chitosan films impregnated with insulin
      loaded PEG-b-PLA nanoparticles (NPs): a potential approach for buccal delivery of
      macromolecules.
AB  - Mucoadhesive chitosan based films, incorporated with insulin loaded nanoparticles
      (NPs) made of poly(ethylene glycol)methyl ether-block-polylactide (PEG-b-PLA)
      have been developed and characterised. Blank-NPs were prepared by double emulsion
      solvent evaporation technique with varying concentrations of the copolymer (5 and
      10%, w/v). The optimised formulation was loaded with insulin (model protein) at
      initial loadings of 2, 5 and 10% with respect to copolymer weight. The developed
      NPs were analysed for size, size distribution, surface charge, morphology,
      encapsulation efficiency and drug release. NPs showing negative (zeta)-potential
      (<-6 mV) with average diameter> 300 nm and a polydispersity index (P.I.) of ~
      0.2, irrespective of formulation process, were achieved. Insulin encapsulation
      efficiencies of 70% and 30% for NPs-Insulin-2 and NPs-Insulin-5 were obtained,
      respectively. The in vitro release behaviour of both formulations showed a
      classic biphasic sustained release of protein over 5 weeks which was influenced
      by pH of the release medium. Optimised chitosan films embedded with 3mg of
      insulin loaded NPs were produced by solvent casting with homogeneous distribution
      of NPs in the mucoadhesive matrix, which displayed excellent physico-mechanical
      properties. The drug delivery system has been designed as a novel platform for
      potential buccal delivery of macromolecules.

PMID- 22405988
TI  - Dual function of tributyrin emulsion: solubilization and enhancement of
      anticancer effect of celecoxib.
AB  - Tributyrin, a triglyceride analogue of butyrate, can act as a prodrug of an
      anticancer agent butyrate after being cleaved by intracellular enzymes. We
      recently demonstrated that the emulsion containing tributyrin as an inner oil
      phase possesses a potent anticancer activity. Herein we sought to develop
      tributyrin emulsion as a carrier of celecoxib, a poorly-water soluble drug with
      anticancer activity. Combined treatment of human HCT116 colon cancer cells with
      free celecoxib plus tributyrin emulsion inhibited the cellular proliferation more
      effectively than that of each drug alone, suggesting the possibility of
      tributyrin emulsion as a potential celecoxib carrier. The mean droplet size of
      emulsions tended to increase as the tributyrin content in emulsion increases and
      the concentration of celecoxib loaded in emulsions was affected by tributyrin
      content and the initial amount of celecoxib, but not by the total amount of
      surfactant mixture. The concentration of celecoxib required to inhibit the growth
      of HCT116 and B16-F10 cancer cells by 50% was 2.6- and 3.1-fold lowered by
      loading celecoxib in tributyrin emulsions, compared with free celecoxib. These
      data suggest that the anticancer activity of celecoxib was enhanced by loading in
      tributyrin emulsions, probably due to the solubilization capacity and anticancer
      activity of tributyrin emulsion.

PMID- 22405985
TI  - Targeting NADPH oxidases in vascular pharmacology.
AB  - Oxidative stress is a molecular dysregulation in reactive oxygen species (ROS)
      metabolism, which plays a key role in the pathogenesis of atherosclerosis,
      vascular inflammation and endothelial dysfunction. It is characterized by a loss
      of nitric oxide (NO) bioavailability. Large clinical trials such as HOPE and HPS
      have not shown a clinical benefit of antioxidant vitamin C or vitamin E
      treatment, putting into question the role of oxidative stress in cardiovascular
      disease. A change in the understanding of the molecular nature of oxidative
      stress has been driven by the results of these trials. Oxidative stress is no
      longer perceived as a simple imbalance between the production and scavenging of
      ROS, but as a dysfunction of enzymes involved in ROS production. NADPH oxidases
      are at the center of these events, underlying the dysfunction of other oxidases
      including eNOS uncoupling, xanthine oxidase and mitochondrial dysfunction. Thus
      NADPH oxidases are important therapeutic targets. Indeed, HMG-CoA reductase
      inhibitors (statins) as well as drugs interfering with the renin-angiotensin
      aldosterone system inhibit NADPH oxidase activation and expression. Angiotensin
      converting enzyme (ACE) inhibitors, AT1 receptor antagonists (sartans) and
      aliskiren, as well as spironolactone or eplerenone, have been discussed.
      Molecular aspects of NADPH oxidase regulation must be considered, while thinking
      about novel pharmacological targeting of this family of enzymes consisting of
      several homologs Nox1, Nox2, Nox3, Nox4 and Nox5 in humans. In order to properly
      design trials of antioxidant therapies, we must develop reliable techniques for
      the assessment of local and systemic oxidative stress. Classical antioxidants
      could be combined with novel oxidase inhibitors. In this review, we discuss NADPH
      oxidase inhibitors such as VAS2870, VAS3947, GK-136901, S17834 or plumbagin.
      Therefore, our efforts must focus on generating small molecular weight inhibitors
      of NADPH oxidases, allowing the selective inhibition of dysfunctional NADPH
      oxidase homologs. This appears to be the most reasonable approach, potentially
      much more efficient than non-selective scavenging of all ROS by the
      administration of antioxidants.

PMID- 22405989
TI  - Self-formation of layered neural structures in three-dimensional culture of ES
      cells.
AB  - In vitro neural differentiation culture of embryonic stem cells (ESCs) provides a
      promising tool for preparing neural cells for replacement therapies and a
      versatile system for understanding mechanisms of neurogenesis. Consistent with
      the neural-default model, neural differentiation spontaneously occurs in ESCs
      cultured in medium containing minimal extrinsic signals. Both adherent monolayer
      culture and floating aggregation culture can be used for ESC conversion into
      neural progenitors. The floating aggregation culture has an advantage for
      recapitulating the formation of three-dimensional (3D) neural tissue structure
      such as layer formation. In this article, we review recent progress in neural
      differentiation culture of ESCs using 3D culture, focusing on self-organization
      phenomena of stratified cortex and retinal tissues. These self-organizing
      processes are driven by both cell intrinsic programs and local cell-cell
      interactions. A simple in vitro system using ESCs is useful for elucidating
      mechanistic dynamics in the complex orchestration of neural development.

PMID- 22405990
TI  - [Heart involvement in sarcoglycanopathies].
AB  - Sarcoglycanopathies (SG) are autosomic recessive muscular dystrophies, secondary
      to mutations of the sarcoglycan complex. Clinical pictures include muscle
      weakness affecting mainly the proximal limb girdle musculature. We review heart
      involvement in this group of disease.

PMID- 22405991
TI  - [Ischemic stroke related to pauci-symptomatic acute aortic dissection. Risks of
      intravenous thrombolysis].
AB  - INTRODUCTION: Acute aortic dissection involving the cervical arteries often
      induces cerebral infarction. In this context, there is a high risk of hemorrhage
      and thrombolytics are contra-indicated. OBSERVATION: We report two patients with
      a cerebral infarction which occurred after a pauci-symptomatic and undiagnosed
      aortic dissection treated with thrombolysis. The outcome was poor for both
      patients. DISCUSSION: Ischemic strokes related to acute aortic dissection often
      involve the right carotid artery territory and may manifest without pain. A
      systematic assessment of supra-aortic arteries might help to identify the
      underlying diagnosis. CONCLUSION: Acute aortic dissection should be
      systematically mentioned in the management of the acute ischemic stroke.

PMID- 22405992
TI  - Suction loss during thin-flap femto-LASIK: management and beneficial refractive
      effect of the epithelium.
AB  - We report the case of a 42-year-old man who experienced loss of suction during
      thin-flap femto-laser in situ keratomileusis, leading to a stromal step in the
      superior cornea where the cutting was stopped. The procedure was converted to
      photorefractive keratectomy 2 weeks later. Management of the loss of suction and
      the beneficial role played by the epithelium postoperatively on the refractive
      outcomes are discussed. FINANCIAL DISCLOSURE: No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 22405993
TI  - Refractive outcomes of laser-assisted subepithelial keratectomy for myopia,
      hyperopia, and astigmatism using a 213 nm wavelength solid-state laser.
AB  - PURPOSE: To study the visual and refractive outcomes after laser-assisted
      subepithelial keratectomy (LASEK) performed with a 213 nm solid-state laser for a
      broad range of refractive errors. SETTING: Private practice, Jersey, United
      Kingdom. DESIGN: Case series. METHODS: The LASEK was performed using a Pulzar Z1
      213 nm solid-state laser. Manifest refraction and uncorrected (UDVA) and
      corrected (CDVA) distance visual acuities were measured preoperatively and 2 and
      6 months postoperatively. Accuracy, safety, efficacy, and stability were assessed
      at 6 months. RESULTS: The study enrolled 245 eyes (134 patients). The
      preoperative spherical equivalent (SE) refractive errors ranged from -9.50 to
      +6.50 diopters (D); 24 eyes had more than 2.50 D of astigmatism. At 6 months,
      60.4% of eyes were within +/-0.25 D of the intended SE, 89.4% were within +/-0.50
      D, and 97.9% were within +/-1.00 D. No eye lost 2 or more lines of CDVA; 95.5% of
      eyes were unchanged or gained 1 line. The mean cylinder power decreased from 
      0.98 +/- 1.17 D to -0.14 +/- 0.28 DC at 6 months. The mean SE was unchanged over
      the follow-up period; -0.01 +/- 0.57 D and -0.01 +/- 0.55 D at 2 months and 6
      months, respectively. CONCLUSION: Laser-assisted subepithelial keratectomy
      performed using the 213 nm wavelength solid-state laser was safe, accurate, and
      effective for the treatment of myopia, hyperopia, and astigmatism. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 22405994
TI  - Repeated sessions of sub-threshold 20-Hz rTMS. Potential cumulative effects in a
      brain-injured patient.

PMID- 22405995
TI  - Selenium and mercury molar ratios in saltwater fish from New Jersey: individual
      and species variability complicate use in human health fish consumption
      advisories.
AB  - Balancing risk versus benefits to humans and other organisms from consuming fish
      is a national concern in the USA, as well as in many other parts of the world.
      Protecting public health is both a federal and state responsibility, and states
      respond by issuing fish consumption advisories, particularly for mercury.
      Recently it has been emphasized that the protective role of selenium against
      mercury toxicity depends on their molar ratios, which should be evaluated as an
      indication of selenium's protective capacity, and incorporated in risk
      assessments for fish consumption. However, there is no single "protective" ratio
      agreed upon. In this paper we examine the selenium:mercury (Se:Hg) molar ratios
      in a wide range of saltwater fish caught and eaten by recreational fishers along
      the New Jersey coast. We were particularly interested in interspecific and
      intraspecific variability, and whether the molar ratios were consistent within a
      species, allowing for its use in managing risk. The selenium-mercury molar ratio
      showed significant variation among and within fish species. The molar ratio
      decreased with the size of the fish species, decreased with the mercury levels,
      and within a fish species, the selenium:mercury ratio decreased with fish size.
      As an essential element, selenium undergoes some homeostatic regulation, but it
      is also highly toxic. Within species, mercury level tends to increase with size,
      accounting for the negative relationship between size and ratio. This variability
      may make it difficult to use the selenium:mercury molar ratio in risk assessment,
      risk management, and risk communication at this time, and more information is
      needed on how mercury and selenium actually interact and on the relationship
      between the molar ratios and health outcomes.

PMID- 22405996
TI  - Lower acetylcholinesterase activity among children living with flower plantation
      workers.
AB  - BACKGROUND: Children of workers exposed to pesticides are at risk of secondary
      pesticide exposure. We evaluated the potential for lower acetylcholinesterase
      activity in children cohabiting with fresh-cut flower plantation workers, which
      would be expected from organophosphate and carbamate insecticide exposure.
      Parental home surveys were performed and acetylcholinesterase activity was
      measured in 277 children aged 4-9 years in the Secondary Exposure to Pesticides
      among Infants, Children and Adolescents (ESPINA) study. Participants lived in a
      rural county in Ecuador with substantial flower plantation activity. RESULTS:
      Mean acetylcholinesterase activity was 3.14 U/ml, standard deviation (SD) of
      0.49. It was lower by 0.09 U/ml (95% confidence interval (CI) -0.19, -0.001) in
      children of flower workers (57% of participants) than non-flower workers'
      children, after adjustment for gender, age, height-for-age, hemoglobin
      concentration, income, pesticide use within household lot, pesticide use by
      contiguous neighbors, examination date and residence distance to nearest flower
      plantation. Using a 4 level polychotomous acetylcholinesterase activity dependent
      variable, flower worker cohabitation (vs. not) had odds ratio 3.39 (95% CI 1.19,
      9.64) for being <15th percentile compared to the highest tertile. Children
      cohabitating for >=5 years (vs. never) had OR of 4.11 (95% CI: 1.17, 14.38) of
      AChE activity within <15th percentile compared to the highest tertile.
      CONCLUSIONS: Cohabitation with a flower worker was related to lower
      acetylcholinesterase activity in children. This supports the hypothesis that the
      amount of take-home pesticides from flower workers suffices to decrease
      acetylcholinesterase activity, with lower activity associated with longer
      exposure.

PMID- 22405997
TI  - Prepartum vaginal/anorectal Group B Streptococcus screening: improvement of the
      enrichment step by the broth additive RambaQUICK StrepB.
AB  - We used RambaQUICK StrepB in enrichment broth with samples taken from 31 pregnant
      women and compared its performance to that of standard enrichment media.
      RambaQUICK StrepB shortened the required incubation time and raised the
      sensitivity of streptococcal screening by 1.6 fold.

PMID- 22405998
TI  - Epithelial Na(+) channel regulation by cytoplasmic and extracellular factors.
AB  - Electrogenic Na(+) transport across high resistance epithelial is mediated by the
      epithelial Na(+) channel (ENaC). Our understanding of the mechanisms of ENaC
      regulation has continued to evolve over the two decades following the cloning of
      ENaC subunits. This review highlights many of the cellular and extracellular
      factors that regulate channel trafficking or gating.

PMID- 22405999
TI  - WNK kinases and the kidney.
AB  - In the kidney, the renal tubule plays a major role in maintaining fluid and
      electrolyte balance. This balance is achieved by an interplay between various
      hormones and nerves that signal changes throughout the body and transfer these
      signals to transport proteins. Increased or reduced activity of these
      transporters helps to restore homeostasis, but can also contribute to disease
      (e.g. sodium retention in hypertension). In recent years, it has become clear
      that the signal transfer to transporters is largely mediated by kinases. Among
      these, WNK kinases (With No lysine=K) stand out, because they regulate the major
      sodium and potassium transporters in the distal nephron. Moreover, mutations in
      genes encoding WNK kinases result in an inherited form of salt-sensitive
      hypertension with hyperkalemia, illustrating their important role in sodium,
      potassium, and blood pressure regulation. More recently, WNK kinases were found
      to play a role in acquired forms of hypertension as well. Together, the evolving
      insight in the kinase regulation of ion transport is providing new insights in
      the longstanding question how salt and blood pressure are related. Here, we
      review the current models of how WNK kinases regulate the various transport
      proteins and which roles they play in health and disease.

PMID- 22406001
TI  - Acute acalculous cholecystitis complicated by MRCP-confirmed Mirizzi syndrome: A
      case report.
AB  - INTRODUCTION: Acute acalculous cholecystitis can be complicated by extrinsic
      compression of the common hepatic/common bile duct by the enlarged and inflamed
      gallbladder followed by jaundice. Its mechanism is very similar to that of
      Mirizzi syndrome, when the bile duct is compressed from outside due to a stone
      impacted in the gallbladder neck or cystic duct. This complication of acalculous
      cholecystitis is rare, with very little number of published cases. PRESENTATION
      OF A CASE: We present a patient with compression of the common hepatic duct by an
      inflamed and enlarged gallbladder in the absence of stones as confirmed by
      magnetic resonance cholangiopancreatography (MRCP). Acute cholecystitis and
      jaundice resolved after conservative treatment, and the changes were shown by a
      follow-up MRCP five months later. DISCUSSION: We were able to find only three
      similar cases reported in the literature. In these cases, compression of the
      common hepatic/common bile duct by the inflamed gallbladder was confirmed by
      endoscopic retrograde cholangiopancreatography and intraoperatively. Terminology
      to describe this condition has not been agreed upon. We consider it as a special
      kind of Mirizzi syndrome. CONCLUSION: To the best of our knowledge, this is the
      first reported case of MRCP-confirmed Mirizzi syndrome in acute acalculous
      cholecystitis.

PMID- 22406002
TI  - Inflammatory biomarkers predict depressive, but not anxiety symptoms during
      aging: the prospective Sydney Memory and Aging Study.
AB  - This study addresses the paucity of research on the prospective relationship
      between a range of inflammatory markers and symptoms of depression and anxiety
      during aging. In the Sydney Memory and Aging Study, the relationships between
      remitted depression, current and first onset of symptoms of depression or anxiety
      (Geriatric Depression Scale and Goldberg Anxiety Scale (GDS, GAS), and markers of
      systemic inflammation (C-reactive protein (CRP), interleukins-1beta, -6, -8, -10,
      -12, plasminogen activator inhibitor-1 (PAI-1), serum amyloid A, tumor necrosis
      factor-alpha, and vascular adhesion molecule-1) were investigated. The sample
      consists of N=1037 non-demented community-dwelling elderly participants aged 70
      90 years assessed at baseline and after 2-years. All analyses were adjusted for
      gender, age, years of education, total number of medical disorders diagnosed by a
      doctor, cardiovascular disorders, endocrine disorders, smoking, body mass index,
      currently using anti-depressants, NSAIDS or statins and diabetes mellitus. The
      results show a significant linear relationship between increasing levels of IL-6
      and depressive symptoms at baseline only, whereas IL-8 was associated with
      depressed symptoms at baseline and at 2 years follow-up. In addition, IL-8 was
      associated with first onset of mild to moderate depressive symptoms over 2 years.
      Logistic regression analyses showed that PAI-1 (OR=1.37, 95% CI=1.10-1.71,
      p=0.005) was associated with remitted depression. Results for anxiety symptoms
      were negative. The findings are suggestive of IL-6 and IL-8 being associated with
      current symptoms and IL-8 being associated with first onset of depressive
      symptoms, whereas PAI-1 could be regarded as a marker of remitted depression.

PMID- 22406000
TI  - Renal cancer: oxygen meets metabolism.
AB  - Over the last two decades molecular studies of inherited tumor syndromes that are
      associated with the development of kidney cancer have led to the identification
      of genes and biochemical pathways, which play key roles in the malignant
      transformation of renal epithelial cells. Some of these findings have broad
      biological impact and extend beyond renal cancer. This review's focus is on the
      von Hippel-Lindau (VHL)/hypoxia-inducible factor (HIF) oxygen-sensing pathway and
      its role in physiology, energy metabolism and tumorigenesis.

PMID- 22406003
TI  - Lys48-linked TAK1 polyubiquitination at lysine-72 downregulates TNFalpha-induced
      NF-kappaB activation via mediating TAK1 degradation.
AB  - Protein kinases are important regulators of intracellular signal transduction
      pathways and play critical roles in diverse cellular processes. TAK1, a member of
      the MAPKKK family, is essential for TNFalpha-induced NF-kappaB activation.
      Phosphorylation and Lys(63)-linked polyubiquitination (polyUb) of TAK1 are
      critical for its activation. However, whether TAK1 is regulated by
      polyubiquitination-mediated protein degradation after its activation remains
      unknown. Here we report that TNFalpha induces TAK1 Lys(48) linked
      polyubiquitination and degradation at the later time course. Furthermore, we
      provide direct evidence that TAK1 is modified by Lys(48)-linked
      polyubiquitination at lysine-72 by mass spectrometry. A K72R point mutation on
      TAK1 abolishes TAK1 Lys(48)-linked polyubiquitination and enhances TAK1/TAB1 co
      overexpression-induced NF-kappaB activation. As expected, TAK1 K72R mutation
      inhibits TNFalpha-induced Lys(48)-linked TAK1 polyubiquitination and degradation.
      TAK1 K72R mutant prolongs TNFalpha-induced NF-kappaB activation and enhances
      TNFalpha-induced IL-6 gene expression. Our findings demonstrate that TNFalpha
      induces Lys(48)-linked polyubiquitination of TAK1 at lysine-72 and this
      polyubiquitination-mediated TAK1 degradation plays a critical role in the
      downregulation of TNFalpha-induced NF-kappaB activation.

PMID- 22406005
TI  - Using the Griess colorimetric nitrite assay for measuring aliphatic beta
      nitroalcohols.

PMID- 22406004
TI  - Fatigue and sleep quality are associated with changes in inflammatory markers in
      breast cancer patients undergoing chemotherapy.
AB  - Fatigue and sleep disturbances are two of the most common and distressing
      symptoms reported by cancer patients. Fatigue and sleep are also correlated with
      each other. While fatigue has been reported to be associated with some
      inflammatory markers, data about the relationship between cancer-related sleep
      disturbances and inflammatory markers are limited. This study examined the
      relationship between fatigue and sleep, measured both subjectively and
      objectively, and inflammatory markers in a sample of breast cancer patients
      before and during chemotherapy. Fifty-three women with newly diagnosed stage I
      III breast cancer scheduled to receive at least four 3-week cycles of
      chemotherapy participated in this longitudinal study. Fatigue was assessed with
      the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), sleep
      quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and objective
      sleep was measured with actigraphy. Three inflammatory markers were examined:
      Interleukin-6 (IL-6), Interleukin-1 receptor antagonist (IL-1RA) and C-reactive
      protein (CRP). Data were collected before (baseline) and during cycle 1 and cycle
      4 of chemotherapy. Compared to baseline, more fatigue was reported, levels of IL
      6 increased and IL-1RA decreased during chemotherapy. Reports of sleep quality
      remained poor. Mixed model analyses examining changes from baseline to each
      treatment time point revealed overall positive relationships between changes in
      total MFSI-SF scores and IL-6, between changes in total PSQI scores and IL-6 and
      IL-1RA, and between total wake time at night and CRP (all p's<0.05). These
      relationships suggest that cancer-related fatigue and sleep disturbances may
      share common underlying biochemical mechanisms.

PMID- 22406006
TI  - Focus on molecules: sulfotyrosine.

PMID- 22406007
TI  - Auxin and ethylene: collaborators or competitors?
AB  - The individual roles of auxin and ethylene in controlling the growth and
      development of young seedlings have been well studied. In recent years, these two
      hormones have been shown to act synergistically to control specific growth and
      developmental processes, such as root elongation and root hair formation, as well
      as antagonistically in other processes, such as lateral root formation and
      hypocotyl elongation. This review examines the growth and developmental processes
      that are regulated by crosstalk between these two hormones and explores the
      mechanistic basis for the regulation of these processes. The emerging trend from
      these experiments is that ethylene modulates auxin synthesis, transport, and
      signaling with unique targets and responses in a range of tissues to fine-tune
      seedling growth and development.

PMID- 22406008
TI  - Repeated measurements, bilateral observations and pseudoreplicates, why does it
      matter?

PMID- 22406009
TI  - A framework for the comparison of mobile patient monitoring systems.
AB  - A mobile patient monitoring system makes use of mobile computing and wireless
      communication technologies for continuous or periodic measurement and analysis of
      biosignals of a mobile patient. In a number of trials these systems have
      demonstrated their user-friendliness, convenience and effectiveness for both
      patients and healthcare professionals. In this paper we propose a generic
      architecture, associated terminology and a classificatory framework for comparing
      mobile patient monitoring systems. We then apply this comparison framework to
      classify six mobile patient monitoring systems selected according to the
      following criteria: use of diverse mobile communication techniques, evidence of
      practical trials and availability of sufficient published scientific information.
      We also show how to use this framework to determine feature sets of prospective
      real-time mobile patient monitoring systems using the example of epilepsy
      monitoring. This paper is aimed at both healthcare professionals and computer
      professionals. For healthcare professionals, this paper provides a general
      understanding of technical aspects of the mobile patient monitoring systems and
      highlights a number of issues implied by the use of these systems. The proposed
      framework for comparing mobile patient monitoring systems can be used by
      healthcare professionals to determine feature sets of prospective mobile patient
      monitoring systems to address particular healthcare related needs. Computer
      professionals are expected to benefit by gaining an understanding of the latest
      developments in the important emerging application area of mobile patient
      monitoring systems.

PMID- 22406010
TI  - Genes under positive selection in a model plant pathogenic fungus, Botrytis.
AB  - The rapid evolution of particular genes is essential for the adaptation of
      pathogens to new hosts and new environments. Powerful methods have been developed
      for detecting targets of selection in the genome. Here we used divergence data to
      compare genes among four closely related fungal pathogens adapted to different
      hosts to elucidate the functions putatively involved in adaptive processes. For
      this goal, ESTs were sequenced in the specialist fungal pathogens Botrytis
      tulipae and Botrytis ficariarum, and compared with genome sequences of Botrytis
      cinerea and Sclerotinia sclerotiorum, responsible for diseases on over 200 plant
      species. A maximum likelihood-based analysis of 642 predicted orthologs detected
      21 genes showing footprints of positive selection. These results were validated
      by resequencing nine of these genes in additional Botrytis species, showing they
      have also been rapidly evolving in other related species. Twenty of the 21 genes
      had not previously been identified as pathogenicity factors in B. cinerea, but
      some had functions related to plant-fungus interactions. The putative functions
      were involved in respiratory and energy metabolism, protein and RNA metabolism,
      signal transduction or virulence, similarly to what was detected in previous
      studies using the same approach in other pathogens. Mutants of B. cinerea were
      generated for four of these genes as a first attempt to elucidate their
      functions.

PMID- 22406011
TI  - The validation of a food label literacy questionnaire for elementary school
      children.
AB  - OBJECTIVE: To determine the reliability and validity of a 10-item questionnaire,
      the Food Label Literacy for Applied Nutrition Knowledge questionnaire. METHODS:
      Participants were elementary school children exposed to a 90-minute school-based
      nutrition program. Reliability was assessed via Cronbach alpha and intraclass
      correlation coefficient (ICC). Validity was assessed comparing the
      questionnaire's food choices using an objective metric of nutrition quality, the
      Overall Nutritional Quality Index (ONQI), via t test. Statistical significance
      was set at .05. RESULTS: Four hundred ninety-nine children participated, 51% were
      female, and the average age was 8.6 (+/- 0.9) years. Cronbach alpha = .77 and ICC
      = 0.68 (between administrations) were observed. ONQI scores of correct responses
      were significantly higher when compared to the ONQI scores of incorrect responses
      (27.4 +/- 9.4 vs 16.2 +/- 9.4; P = .01). CONCLUSIONS AND IMPLICATIONS: The Food
      Label Literacy for Applied Nutrition Knowledge questionnaire was found to be both
      reliable and a valid measure of food label literacy in children taught the
      Nutrition Detectives program.

PMID- 22406013
TI  - Revised WIC food package improves diets of WIC families.
AB  - OBJECTIVE: To explore the impact of the new Special Supplemental Nutrition
      Program for Women, Infants and Children (WIC) food package on WIC participant
      consumption of fruit, vegetables, whole-grain food, and lower-fat milk. DESIGN:
      Telephone surveys of cross-sectional samples of California WIC families before
      and after the changes to the food package. PARTICIPANTS: Random samples of
      pregnant or postpartum women and/or caregivers of children enrolled in WIC: 3,004
      in September, 2009; 2,996 in March, 2010. MAIN OUTCOME MEASURES: Consumption of
      fruit, vegetables, whole-grain food, and lower-fat milk. ANALYSIS: Comparisons of
      outcome variables were made by examining the differences by time point, adjusted
      for sociodemographic variables, using ANOVA (for means) or logistic regression
      (for percentages). RESULTS: Following the changes to the WIC food package,
      consumption of whole-grain food increased by 17.3 percentage points, a 51%
      increase over baseline. Caregivers and children who usually consumed whole milk
      decreased by 15.7 and 19.7 percentage points, respectively, a 60%-63% reduction
      over baseline. Accompanying increases in lower-fat milk consumption were
      demonstrated. Small but significant increases in consumption of fruits and
      vegetables were also observed. CONCLUSIONS AND IMPLICATIONS: Federal policy
      changes to the WIC program had the intended effect of increasing consumption of
      the prescribed food items.

PMID- 22406012
TI  - Evaluating the dissemination of Body & Soul, an evidence-based fruit and
      vegetable intake intervention: challenges for dissemination and implementation
      research.
AB  - OBJECTIVE: To evaluate whether the evidence-based Body & Soul program, when
      disseminated and implemented without researcher or agency involvement and
      support, would achieve results similar to those of earlier efficacy and
      effectiveness trials. DESIGN: Prospective group randomized trial. SETTING:
      Churches with predominantly African American membership. PARTICIPANTS: A total of
      1,033 members from the 15 churches completed baseline surveys. Of these
      participants, 562 (54.4%) completed the follow-up survey 6 months later.
      INTERVENTION: Church-based nutrition program for African Americans that included
      pastoral involvement, educational activities, church environmental changes, and
      peer counseling. MAIN OUTCOME MEASURE: Daily fruit and vegetable (FV) intake was
      assessed at pre- and posttest. ANALYSIS: Mixed-effects linear models. RESULTS: At
      posttest, there was no statistically significant difference in daily servings of
      FVs between the early intervention group participants compared to control group
      participants (4.7 vs 4.4, P = .38). Process evaluation suggested that added
      resources such as technical assistance could improve program implementation.
      CONCLUSIONS AND IMPLICATIONS: The disseminated program may not produce
      improvements in FV intake equal to those in the earlier efficacy and
      effectiveness trials, primarily because of a lack of program implementation.
      Program dissemination may not achieve public health impact unless support systems
      are strengthened for adequate implementation at the church level.

PMID- 22406014
TI  - Muscle loading and activation of the shoulder joint during humeral external
      rotation by pulley and variable resistance.
AB  - BACKGROUND: The aim of the study was to evaluate differences in the loading of
      glenohumeral joint muscles between a cable pulley machine (CP) and variable
      resistance machine (VR) during axial humeral external rotation. METHODS: Eleven
      healthy male subjects took part in the study. Intramuscular electromyography from
      five muscles of the shoulder (medial deltoid, supraspinatus, infraspinatus and
      upper part of the trapezius), torque and power output was measured at different
      rotation angles and with different loads (10%, 50% and 100% of 1RM). Also the
      compressive and shear force in the glenohumeral joint was analyzed at the
      horizontal level at angles of rotation. External rotation was performed with a
      self-selected velocity on the scapular plane. FINDINGS: In the CP the range of
      movement became narrower than in the VR with increasing workload (P<0.05). The
      activity of the infraspinatus did not grow in the CP after 50% load, while it did
      in the VR (P<0.01). The upper part of the trapezius was activated less in the CP
      than in the VR (P<0.01) machine when using 50% and 100% loads. In comparison with
      the CP, the shear forces that pull the head of the humerus in a posterior
      direction were more evenly distributed in the VR than in the CP at different
      angles of rotation (P<0.001). INTERPRETATION: The VR seems to make a broader
      range of motion possible, lager activation the primary external rotators and
      evenly distributed shear forces than the CP. However, performing the exercise
      with VR and high load also activates the upper part of the trapezius. RELEVANCE:
      These findings can be used in the development of exercise designs, methods and
      equipment for shoulder injury rehabilitation.

PMID- 22406015
TI  - Whole-body vibration increases upper and lower body muscle activity in older
      adults: potential use of vibration accessories.
AB  - The current study examined the effects of whole-body vibration (WBV) on upper and
      lower body muscle activity during static muscle contractions (squat and bicep
      curls). The use of WBV accessories such as hand straps attached to the platform
      and a soft surface mat were also evaluated. Surface electromyography (sEMG) was
      measured for the medial gastrocnemius (MG), vastus lateralis (VL), and biceps
      brachii (BB) muscles in fourteen healthy older adults (74.8+/-4.5 years; mean+/
      SD) with a WBV stimulus at an acceleration of 40 m s(-2) (30 Hz High, 2.5 mm or
      46 Hz Low, 1.1 mm). WBV increased lower body (VL and MG) sEMG vs baseline (no
      WBV) though this was decreased with the use of the soft mat. The addition of the
      bicep curl with hand straps had no effect on lower body sEMG. WBV also increased
      BB sEMG vs baseline which was further increased when using the hand straps. There
      was no upper body effect of the soft mat. This study demonstrates WBV increases
      both lower and upper body muscle activity in healthy older adults. Moreover, WBV
      accessories such as hand straps attached to the platform or a soft surface mat
      may be used to alter exercise intensity.

PMID- 22406016
TI  - The neural dissociation of subjective valuation from choice processes in
      intertemporal choice.
AB  - During intertemporal choice, the neurobiological mechanism could include two
      process stages: a multicomponent valuation stage and a choice stage. Previous
      studies suggested that the contribution of subjective valuation may be recruited
      during the valuation stage, but that was absent during the choice stage. However,
      no studies have directly demonstrated the neural dissociation of subjective
      valuation from choice processes in intertemporal choice. Combining a novel,
      temporally distributed discounting task with event-related fMRI, we examined this
      hypothesis whether the neural substrates of subjective valuation were activated
      in the valuation stage, not in the choice stage. Behaviorally, participants
      discounted delayed rewards following a hyperbolic discounting function, and
      discount rates varied considerably between participants, reflecting different
      individual preferences. Ventral striatum (VStr), ventralmedial prefrontal
      cortical (vmPFC), and posterior cingulate cortical (PCC) activation were
      correlated strongly with the subjective valuation in the valuation stage, whereas
      dorsolateral prefrontal cortical (DLPFC), and inferior frontal gyrus (IFG) were
      correlated with choice processes in the choice stage. These findings suggest that
      mesolimbic dopamine projection regions show greater sensitivity to the subjective
      value during the valuation stage, and are absent during the choice stage, which
      demonstrates the neural dissociation of subjective valuation from choice
      processes in intertemporal choice.

PMID- 22406017
TI  - The right time, the right place: will targeting human cancer-associated mutations
      to the mouse provide the perfect preclinical model?
AB  - Over the past 10 years the realisation that genetic mouse models of cancer may
      play a key role in preclinical drug development has gained strong momentum.
      Moreover sequencing studies of human tumours have provided key insights into the
      mutational complexity of epithelial cancer, unleashing important clues for
      researchers to generate accurate genetically engineered mouse (GEM) models of
      cancer. Thus by targeting multiple cancer associated human mutations to the
      appropriate murine epithelia, mice develop tumours that more closely recapitulate
      the human disease. As a number of excellent models now exist, the next 5-10 years
      will ascertain whether these models will predict response of human cancer to
      intervention. If so they might become the 'gold standard' where all drugs are
      required to be tested in mouse models of disease before proceeding into the
      patient. However, although this principle is very attractive, it is relatively
      untested and here, using examples of prevalent human cancers, we will review the
      latest data on preclinical GEM studies and comment on what challenges are left to
      overcome.

PMID- 22406019
TI  - A statistical model to evaluate the effectiveness of PM2.5 emissions control
      during the Beijing 2008 Olympic Games.
AB  - A statistical model was developed using satellite remote sensing data and
      meteorological parameters to evaluate the effectiveness of air pollution control
      measures during the 2008 Beijing Olympic Games. Custom satellite retrievals under
      hazy conditions were included in the modeling dataset to represent the air
      pollution levels more accurately. This model explained 70% of the PM(2.5)
      variability during the modeling period from June to October 2008. Using this
      tool, we estimate that the aggressive emission reduction measures alone
      effectively lowered PM(2.5) levels by 20-24 MUg/m(3) or 27-33% on average during
      the Games period, which is substantially greater than those reported previously.
      Since parameters required to develop this model are readily available in most
      cities of the world, it can be quickly applied after other major events to
      evaluate air pollution control policy.

PMID- 22406020
TI  - Soil mutagenicity as a strategy to evaluate environmental and health risks in a
      contaminated area.
AB  - Soil can be a storage place and source of pollutants for interfacial
      environments. This study looked at a site contaminated with wood preservatives as
      a source of mutagens, defined routes and extent of the dispersion of these
      contaminants by particle remobilization and atmospheric deposition, considering
      an evaluation of risk to human health by quantifying mutagenic risk. Soil
      sampling sites were chosen at gradually increasing distances (150, 500 and 1700m)
      from SI (industrial area pool) and indoor dust (pool in an area at risk at 385m
      and at 1700m). Mutagenesis was evaluated in the Salmonella/microsome assay, TA98,
      TA97a and TA100 strains with and without S9 mix, YGs strains 1041, 1042 and 1024
      for nitrocompounds. Acid extracts were analyzed to define the effects of metals
      and organics for polycyclic aromatic hydrocarbons (PAHs) and nitroderivates,
      besides concentrations of these compounds and pentachlorophenol (PCP). Risk to
      human health was obtained from the relation between the quantified potential of
      mutagenic risk and estimated soil ingestion for children according to USEPA.
      Metal concentrations showed a gradient of responses with As, Cr and Cu (total
      metal) or Cr and Cu (fraction available) higher for SI. However, mutagenic
      effects of the mixtures did not show this grading. Site SR1700, without a
      response, was characterized as a reference. In organic extracts, the mutagenesis
      responses showed the mobility of these compounds from the source. In the
      surrounding area, a smaller pattern similar to SI was observed at SR150, and at
      the other sites elevated values of direct mutagenesis at SR500 and diminished
      effects at SR1700. Tests with YG strains indicated that nitrated compounds have a
      significant effect on the direct mutagenesis found, except SR500. The
      investigation of indoor dust in the surrounding area enabled confirmation of the
      particle resuspension route and atmospheric deposition, showing responses in
      mutagenicity biomarkers, PAH concentrations and PCP dosage similar to SI. The
      range of values obtained, considering the soil masses needed to induce
      mutagenicity was 0.02 to 0.33g, indicating a high risk associated with human
      populations exposed, since these values found surpass the standard estimate of
      200mg/day of rate of soil ingestion for children according to USEPA. The study
      showed that it is essential to evaluate the extent of contamination from the soil
      to delimit remedial measures and avoid damage to the ecological balance and to
      human health.

PMID- 22406021
TI  - Fate, distribution, and contrasting temporal trends of perfluoroalkyl substances
      (PFASs) in Lake Ontario, Canada.
AB  - Lake Ontario water and sediment collected from tributary, nearshore, and open
      lake sites were analyzed for perfluoroalkyl substances (PFASs), namely
      perfluoroalkyl carboxylic acids (PFCAs, F(CF(2))(n)CO(2)(-); n=6-11,13) and
      perfluoroalkane sulfonic acids (PFSAs, F(CF(2))(n)SO(3)(-); n=6,8,10). Survey
      results of surface sediment and water indicated that shorter chained PFASs were
      predominant in and near urban/industrial area watersheds, while longer chained
      PFASs were predominant in fine-grained sediment from major depositional basins.
      Niagara River suspended solids (1981-2006) demonstrated temporal trends that may
      have been influenced by recent changes in North American production and use of
      PFASs. Perfluorooctane sulfonate (PFOS) reached a peak concentration in 2001 of
      1.1 ng/g, followed by a decrease from 2001 to 2006 (half-life=9 years).
      Perfluorooctanoic acid (PFOA) increased from 2001 to 2006 (doubling time= 2
      years) reaching a peak concentration of 0.80 ng/g. In contrast, three sediment
      cores from western, central, and eastern Lake Ontario showed increasing temporal
      trends to surface sediment for all PFASs. PFOA and PFOS concentrations increased
      from 1988 to 2004 (doubling time= ~ 4 years) in the western Lake Ontario core.
      The observed variations in temporal trends from different environmental
      compartments may be a result of the physico-chemical properties of PFASs, ongoing
      emissions, and the environmental transformation and degradation of PFAS precursor
      compounds.

PMID- 22406018
TI  - Active human retrotransposons: variation and disease.
AB  - Mobile DNAs, also known as transposons or 'jumping genes', are widespread in
      nature and comprise an estimated 45% of the human genome. Transposons are divided
      into two general classes based on their transposition intermediate (DNA or RNA).
      Only one subclass, the non-LTR retrotransposons, which includes the Long
      INterspersed Element-1 (LINE-1 or L1), is currently active in humans as indicated
      by 96 disease-causing insertions. The autonomous LINE-1 is capable of
      retrotransposing not only a copy of its own RNA in cis but also other RNAs (Alu,
      SINE-VNTR-Alu (SVA), U6) in trans to new genomic locations through an element
      encoded reverse transcriptase. L1 can also retrotranspose cellular mRNAs,
      resulting in processed pseudogene formation. Here, we highlight recent reports
      that update our understanding of human L1 retrotransposition and their role in
      disease. Finally we discuss studies that provide insights into the past and
      current activity of these retrotransposons, and shed light on not just when, but
      where, retrotransposition occurs and its part in genetic variation.

PMID- 22406022
TI  - Scapulothoracic dissociation.

PMID- 22406023
TI  - Phlegmasia cerulea dolens in a patient with an inferior vena cava filter.

PMID- 22406024
TI  - Breath analyzer screening of emergency department patients suspected of alcohol
      intoxication.
AB  - BACKGROUND: Acute alcohol intoxication is a frequent cause of emergency
      department (ED) visits. Evaluating a patient's alcohol intoxication is commonly
      based on both a physical examination and determination of blood alcohol
      concentration (BAC). OBJECTIVE: To demonstrate the feasibility and usefulness of
      using a last-generation infrared breath analyzer as a non-invasive and rapid
      screening tool for alcohol intoxication in the ED. METHODS: Adult patients
      suspected of acute alcohol intoxication were prospectively enrolled over 10 days.
      Breath alcohol concentrations (BrAC) were measured using a handheld infrared
      breath analyzer. BAC was determined simultaneously by automated enzymatic
      analysis of a venous blood sample. The relationship between BAC and BrAC values
      was examined by both linear regression and Bland-Altman analysis. RESULTS: The
      study included 54 patients (mean age 40+/-14 years, sex ratio M/F of 3/1). Breath
      and blood alcohol concentrations ranged from 0 to 1.44 mg/L and from 0 to 4.40
      g/L (0-440 mg/dL), respectively. The mean individual BAC/BrAC ratio was 2615+/
      387, 95% confidence interval 2509-2714, which is 30% higher than the legal ratio
      in France (2000). The correlation between both measurements was excellent: r=0.95
      (0.92-0.97). Linear regression revealed BAC=0.026+1.29 (BrAC*2000) and
      BAC=0.026+0.99 (BrAC*2615). Mean BAC-BrAC differences and limits of agreement
      were 0.49 g/L [-0.35, 1.34] (or 49 mg/dL [-35, 134] and 0.01 g/L [-0.68, 0.71]
      (or 1 mg/dL [-68, 71]), for the 2000 and 2615 ratios, respectively. CONCLUSION:
      The calculated conversion coefficient provided a satisfactory determination of
      blood alcohol concentration. Breath alcohol testing, using appropriate BAC/BrAC
      conversion, different from the legal BAC/BrAC, could be a reliable alternative
      for routine screening and management of alcohol intoxication in the ED.

PMID- 22406025
TI  - Pediatric syncope: National Hospital Ambulatory Medical Care Survey results.
AB  - BACKGROUND: Syncope is a common problem in children and adolescents. The
      diagnostic yield for most tests commonly used in the evaluation of pediatric
      patients with syncope is low. STUDY OBJECTIVE: To examine the epidemiology of
      pediatric patients presenting to United States (US) emergency departments (EDs)
      with a complaint of syncope and compare their initial management to published
      guidelines. METHODS: ED visits from the National Hospital Ambulatory Medical Care
      Survey for 2003-2007 for patients aged 7-18 years were analyzed. Outcome
      variables were diagnostic tests and management of patients presenting with
      syncope. RESULTS: There were 627,489 (95% confidence interval [CI] 527,237
      727,722) ED visits for syncope (0.9% of all ED visits for patients aged 7-18
      years). Patients presenting to the ED for syncope were more commonly female
      (p<0.01), adolescent (13-18 years) (p<0.01), covered by private insurance
      (p=0.01), and more likely to arrive to the ED by ambulance (p<0.01), compared to
      those presenting with other complaints. Only 58.1% (95% CI 50.3-66.0%) of syncope
      patients received an electrocardiogram, and 26.5% (95% CI 18.2-34.7%) received a
      computed tomography (CT) or magnetic resonance imaging (MRI) scan as part of
      their diagnostic work-up. CONCLUSIONS: When evaluating pediatric patients
      presenting with syncope, there should be an increased use of the
      electrocardiogram to screen for underlying cardiac abnormalities. There should
      also be a tempered use of CT/MRI imaging in this population.

PMID- 22406026
TI  - Clinical auscultation in noisy environments.

PMID- 22406027
TI  - Free air in the abdomen.

PMID- 22406028
TI  - Supraglottic jet ventilation in difficult airway management.
AB  - BACKGROUND: Supraglottic jet ventilation (SJV) via the "jet endotracheal tube"
      (JET) designed by Wei (WEI JET; Wei Medical LLC, Cherry Hill, NJ) provides
      adequate oxygenation and ventilation during direct laryngoscopy and tracheal
      intubation in animals. It has facilitated intubation in apneic pigs with a
      simulated difficult airway. OBJECTIVE: To report on the first clinical study to
      examine the efficacy of using SJV via the WEI JET, in combination with end-tidal
      CO(2) pressure (PetCO(2)) monitoring during SJV, in maintaining oxygenation
      during direct laryngoscopy, and in facilitating placement of the WEI JET, and
      comparing it to the standard intubation technique using a conventional
      endotracheal tube. The relative safety of using SJV via the WEI JET in airway
      management was also addressed to provide the foundation for a larger-scale
      clinical study using the WEI JET, to be carried out in the future. METHODS:
      Patients in the control group were intubated with a conventional endotracheal
      tube, and patients in the experimental group were intubated with a WEI JET. The
      effectiveness of SJV through a WEI JET in maintaining proper oxygenation, and the
      use of PetCO(2) monitoring to facilitate intubation, were studied and compared to
      the control group. Complications such as sore throat, laryngospasm, and
      barotrauma were recorded during the study and 24 h after extubation. RESULTS: In
      the WEI JET group, pulse oxygen saturation (SpO(2)) was 100% in all patients
      during intubation. No serious complications were detected, and the incidence of
      minor complications was comparable to the control group. Under PetCO(2) guidance,
      100% of patients in the WEI JET group were intubated on the first attempt,
      compared to 30% of Grade III view patients in the control group, who required two
      attempts. CONCLUSION: Using the WEI JET with SJV provides adequate oxygenation
      during tracheal intubation in apneic patients for a prolonged period of time,
      with no difference in complications compared to the standard intubation
      technique. PetCO(2) monitoring facilitated intubation in patients with a Grade
      III glottis view.

PMID- 22406030
TI  - [Measles in pregnancy: a review].
AB  - Although measles is usually considered a benign viral disease of childhood,
      people may be affected whatever their age with severe pneumologic or neurologic
      consequences are more frequent before 5 years old and after 20 years old. The
      consequences of a congenital measles, defined as a newborn eruption within 10
      days after birth, can be dramatic. The incidence of measles has significantly
      decreased since first vaccines were introduced in the late 1960s. In France,
      active immunization for measles is proposed since 1983. Since the beginning of
      2008, France has been experiencing a measles outbreak with more than 17,000
      notified cases. The current measles outbreak affects more particularly very young
      children and young adults and, among these, pregnant women. Measles during
      pregnancy may be severe mainly due to pneumonia. Measles is associated with a
      risk of miscarriage and prematurity, but congenital anomalies have not been
      described. If rash occurs near term, the consequences of congenital measles could
      be severe. Prevention of measles in pregnant women is based on improving
      immunization coverage, currently insufficient to eradicate virus circulation. The
      aim of this review is to state on the latest data concerning measles virus, give
      latest vaccine recommendations, and also to suggest management of measles contact
      or measles infection during pregnancy.

PMID- 22406031
TI  - Beijing Eye Public Health Care Project.
AB  - PURPOSE: The Beijing Eye Public Health Care Project was designed to screen all
      elderly subjects (age 55-85 years) of the rural region of Greater Beijing. It was
      developed as a preparatory step for a telemedicine-based public health care
      system in ophthalmology in China. DESIGN: Population-based public health care
      project. PARTICIPANTS: Elderly subjects (age 55-85 years) of the rural region of
      Greater Beijing. METHODS: Project participants were visited, interviewed, and
      examined by 2500 high school graduates trained as ophthalmic technicians. If
      visual acuity was <0.30, subjects were referred to primary health care centers
      where ocular photographs were taken. Using telemedicine, the photographs were
      transmitted to a reading center and causes for visual impairment were diagnosed.
      MAIN OUTCOME MEASURES: Practicability of a mass screening system in
      ophthalmology; prevalence of visual impairment and causes for it. RESULTS: Out of
      692 323 eligible inhabitants, 562 788 (81.3%) subjects participated. Visual
      impairment in >=1 eye was detected in 54 155 (9.62%) subjects, and among them, 30
      164 (5.36%) subjects had bilateral visual impairment. Ocular fundus photographs
      were taken for 37 281 subjects. Cause for visual impairment was cataract in 19
      163 (3.41%) of all screened subjects, glaucoma in 1606 (0.29%) subjects, diabetic
      retinopathy in 905 (0.16%) subjects, other macular diseases in 2700 (0.48%)
      subjects, pterygium in 1381 (0.25%) subjects, and corneal leukoma in 283 (0.05%)
      subjects. For 5853 (1.04%) subjects, a diagnosis of premature or mature cataract
      was made showing the urgent need of cataract surgery. After cataract surgery,
      visual acuity was >=0.30 in 1464 (91.7%) of 1596 postoperatively reexamined
      subjects. CONCLUSIONS: Using a telemedicine approach, the Beijing Eye Public
      Health Care Project developed, applied and tested an infrastructure for
      ophthalmic mass screening of >500 000 elderly inhabitants with a response rate of
      >80%. Beside cataract, retinal diseases including diabetic retinopathy and
      glaucoma were major causes for visual impairment. FINANCIAL DISCLOSURE(S): The
      authors have no proprietary or commercial interest in any of the materials
      discussed in this article.

PMID- 22406029
TI  - Rare thoracic cancers, including peritoneum mesothelioma.
AB  - Rare thoracic cancers include those of the trachea, thymus and mesothelioma
      (including peritoneum mesothelioma). The aim of this study was to describe the
      incidence, prevalence and survival of rare thoracic tumours using a large
      database, which includes cancer patients diagnosed from 1978 to 2002, registered
      in 89 population-based cancer registries (CRs) and followed-up to 31st December
      2003. Over 17,688 cases of rare thoracic cancers were selected based on the list
      of the RACECARE project. Mesothelioma was the most common tumour (19 per million
      per year) followed by epithelial tumours of the trachea and thymus (1.3 and 1.7,
      respectively). The age standardised incidence rates of epithelial tumours of the
      trachea was double in Eastern and Southern Europe versus the other European
      regions: 2 per million per year. Epithelial tumours of the thymus had the lowest
      incidence in Northern and Eastern Europe and UK and Ireland(1) and somewhat
      higher incidence in Central and Southern Europe.(2) Highest incidence in
      mesothelioma was seen in UK and Ireland(23) and lowest in Eastern Europe.(4)
      Patients with tumours of the thymus had the best prognosis (1-year survival 85%,
      66% at 5 years). Five year survival was lowest for the mesothelioma 5% compared
      to 14% of patients with tumours of the trachea. Mesothelioma was the most
      prevalent rare cancer (12,000 cases), followed by thymus (7000) and trachea
      (1400). Cancer Registry (CR) data play an important role in revealing the burden
      of rare thoracic cancers and monitoring the effect of regulations on asbestos use
      and smoking related policies.

PMID- 22406032
TI  - Atypical presentations of orbital cellulitis caused by methicillin-resistant
      Staphylococcus aureus.
AB  - PURPOSE: To evaluate the epidemiologic and clinical features of orbital
      cellulitis caused by methicillin-resistant Staphylococcus aureus (MRSA). DESIGN:
      Multicenter, retrospective case series. PARTICIPANTS: Fifteen patients with
      culture-positive MRSA orbital cellulitis. METHODS: All recent cases of orbital
      cellulitis at several hospitals and surgical centers were reviewed, and cases
      with culture-positive MRSA from aspirates were identified. The data collected and
      analyzed retrospectively included patient demographics, medical history,
      presenting sign, imaging results, surgical procedure performed, surgical culture
      results, visual acuity at presentation and last follow-up, and duration of
      antibiotics. MAIN OUTCOME MEASURES: Presenting sign, radiographic evidence of
      paranasal sinus disease, radiographic evidence of multiple orbital abscesses,
      presence or absence of antecedent upper respiratory infection, and final visual
      acuity. RESULTS: Fifteen cases were identified. The mean patient age was 31.9
      years (standard deviation, 24.2 years). Lid swelling was the presenting sign in
      14 of 15 patients. No patients had a preceding upper respiratory infection, and
      only 1 patient had antecedent eyelid trauma. Only 3 of 15 patients had documented
      adjacent paranasal sinus disease on imaging. Lacrimal gland abscess or
      dacryoadenitis was the presenting finding in 5 of 15 patients. Multiple orbital
      abscesses were identified in 4 of 15 patients by computed tomography or magnetic
      resonance imaging. Fourteen of 15 cases required surgical intervention. Four of
      15 cases had loss of visual acuity to light perception or worse. All 4 of these
      cases had a delay in referral for surgical intervention. CONCLUSIONS: In these 15
      patients with MRSA orbital cellulitis, the typical clinical setting of orbital
      cellulitis was absent; chiefly, there was no identified antecedent upper
      respiratory illness, nor was there a preceding traumatic injury. Lid swelling in
      the absence of recent upper respiratory illness, lacrimal gland focus, multiple
      orbital abscesses, and lack of adjacent paranasal sinus disease may be predictive
      factors that suggest MRSA as the causative organism of orbital cellulitis.
      FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest
      in any materials discussed in this article.

PMID- 22406033
TI  - Brief morning light treatment for sleep/wake disturbances in older memory
      impaired individuals and their caregivers.
AB  - BACKGROUND: Scheduled exposure to bright light (phototherapy) has been used, with
      varying degrees of success, to treat sleep disruption in older individuals. Most
      of these studies have been done in institutional settings and have used several
      hours of daily light exposure. Such a regimen in the home setting may be
      untenable, especially when the individual with the sleep disruption has memory
      impairment and is being cared for by a family member. As such, we examined the
      effectiveness of a "user-friendly" phototherapy protocol that would be readily
      usable in the home environment. METHODS: We exposed a group of 54 older
      caregiver/care recipient dyads, in which the care recipient had memory
      impairment, to two weeks of morning bright light phototherapy. Dyads were exposed
      to either bright white (~4200 lux) or dim red (~90 lux) light for 30 min every
      day, starting within 30 min of rising. All subjects also received sleep hygiene
      therapy. Objective (actigraphy) and subjective measures of sleep and mood were
      obtained at baseline and at the end of the two weeks of phototherapy. RESULTS: In
      care recipients, actigraphy- and log-determined time in bed and total sleep time
      declined in the active condition (p<0.05, ANOVA); there was no corresponding
      change in subjective insomnia symptoms (p's>0.37, ANOVA). The decrease in the
      time in bed was associated with an earlier out of bed time in the morning
      (p<0.001, Pearson correlation). The decrease in the total sleep time was
      associated with a decrease in sleep efficiency (p<0.001, Pearson correlation) and
      an increase in wake after sleep onset (p<0.001, Pearson correlation). In
      caregivers, there were no differential changes in actigraphic measures of sleep
      (p's>0.05, ANOVA). Actigraphy-measured wake after sleep onset and sleep
      efficiency did, however, improve in both conditions, as did sleepiness, insomnia
      symptoms, and depressive symptomatology (p's<0.05, ANOVA). CONCLUSIONS: Exposure
      to this regimen of phototherapy diminished sleep in older individuals with memory
      impairments. Their caregivers, however, experienced an improvement in sleep and
      mood that appeared independent of the phototherapy and likely due to
      participation in this protocol or the sleep hygiene therapy.

PMID- 22406034
TI  - Trypanosoma brucei solanesyl-diphosphate synthase localizes to the mitochondrion.
AB  - Polyprenyl-diphosphate synthase is a key enzyme in the biosynthesis of
      ubiquinone, a molecule considered essential for a typical eukaryotic cell. Its
      orthologue in the American stercorarian flagellate Trypanosoma cruzi, solanesyl
      diphosphate synthase, has been previously localized into the glycosomes. We
      wondered whether this unique cellular localization is shared by other trypanosome
      species. Using digitonin permeabilization, immunofluorescence and in situ tagging
      techniques, we show that in Trypanosoma brucei, the African salivarian
      flagellate, the enzyme localizes to the mitochondrion.

PMID- 22406035
TI  - Neural sensitivity to novel sounds in the rat's dorsal cortex of the inferior
      colliculus as revealed by evoked local field potentials.
AB  - Evoked local field potentials in response to contralaterally presented tone
      bursts were recorded from the rat's dorsal cortex of the inferior colliculus
      (ICd). An oddball stimulus paradigm was used to study the sensitivity of
      ensembles of neurons in the ICd to novel sounds. Our recordings indicate that
      neuron ensembles in the ICd display stimulus-specific adaptation when a large
      contrast in both frequency and probability of occurrence exists between the two
      tone bursts used for generating an oddball paradigm. A local field potential
      evoked by a tone burst presented as a deviant stimulus has a larger amplitude
      than that evoked by the same sound presented as a standard stimulus. The
      difference between the two responses occurs after the initial rising phases of
      their predominant deflections. The degree of stimulus-specific adaptation
      increases with the rate of sound presentation up to 8/s, the highest rate used in
      this study. A comparison between our results and those from previous studies
      suggests that differences exist between responses to oddball paradigms in the ICd
      and those in the primary auditory cortex, a major source of projection to the
      ICd. These differences suggest that local mechanisms exist in the ICd for
      suppressing neural responses to frequently presented sounds and enhancing
      responses to rarely presented sounds. Thus, the ICd may serve as an important
      component of an integrative circuit in the brain for detecting novel sounds in
      the acoustic environment.

PMID- 22406036
TI  - On flux coupling analysis of metabolic subsystems.
AB  - Genome-scale metabolic networks are useful tools for achieving a system-level
      understanding of metabolism. However, due to their large size, analysis of such
      networks may be difficult and algorithms can be very slow. Therefore, some
      authors have suggested to analyze subsystems instead of the original genome-scale
      models. Flux coupling analysis (FCA) is a well-known method for detecting
      functionally related reactions in metabolic networks. In this paper, we study how
      flux coupling relations may change if we analyze a subsystem instead of the
      original network. We show mathematically that a pair of fully, partially or
      directionally coupled reactions may be detected as uncoupled in certain
      subsystems. Interestingly, this behavior is the opposite of the flux coupling
      changes that may occur due to missing reactions, or equivalently, deletion of
      reactions. Computational experiments suggest that the analysis of plastid (but
      not mitochondrial) subsystems may significantly influence the results of FCA.
      Therefore, the results of FCA for subsystems, especially plastid subsystems,
      should be interpreted with care.

PMID- 22406037
TI  - Comparison of outcomes after HLA-matched sibling and unrelated donor
      transplantation for children with high-risk acute lymphoblastic leukemia.
AB  - We compared outcomes after 94 HLA-matched sibling, 168 unrelated donor bone
      marrow (BM; n = 81 matched and n = 88 mismatched), and 86 cord blood
      transplantations in patients age 1 to 15 years with acute lymphoblastic leukemia
      (ALL) in second complete remission (CR). All patients had their first BM relapse
      within 3 years from diagnosis. Cox regression models were constructed to examine
      for differences in transplant outcome by donor source. Risks of grade 2 to 4
      acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease
      (cGVHD), when compared to HLA-matched sibling transplants, were higher after
      matched unrelated donor BM (relative risk [RR], 2.42; P = .001; RR, 5.12; P <
      .001, respectively), mismatched BM (RR, 3.24; P < .001; RR, 5.19; P < .001,
      respectively), and cord blood (RR, 2.67; P < .001; RR, 2.54; P = .024,
      respectively) transplants. Although nonrelapse mortality was higher after
      transplantation of mismatched unrelated donor BM and cord blood, there were no
      differences in leukemia-free survival (LFS) between HLA-matched sibling and any
      of the unrelated donor transplantations. The 3-year probabilities of LFS were 50%
      after HLA-matched sibling and 44% after matched unrelated BM, and 44% after
      mismatched unrelated BM and 43% after cord blood transplantation. Our
      observations support transplantation of BM or cord blood from a suitably matched
      unrelated donor or cord blood for patients without an HLA-matched sibling with
      ALL in second CR.

PMID- 22406038
TI  - Biological behaviour in mice of Trypanosoma cruzi isolates from Amazonas and
      Parana, Brazil.
AB  - The biological behaviour of 23 Trypanosoma cruzi isolates in Swiss mice was
      compared. Nineteen isolates were obtained from patients in the acute phase of
      Chagas disease (13), sylvatic reservoir hosts (Didelphis marsupialis) (3), and
      triatomine bugs (Rhodnius robustus) (3) from four regions of the State of
      Amazonas (AM). Four isolates were obtained from chronic chagasic patients in the
      State of Parana (PR): three autochthones, and one allochthone from the State of
      Minas Gerais. Only one isolate was unable to infect the mice. The AM and PR
      isolates showed the largest number of significant differences from each other.
      The former had lower mean values in the pre-patent (5.4 days) and patent (4.6
      days) periods (PP), with the parasitaemia (Pmax) reaching a peak of 9.9*10(4)
      blood trypomastigotes (BT)/mL of blood by the 7th day following inoculation. The
      AM isolates also had higher positivity to fresh-blood examination (FBE) (84.1%)
      compared to haemoculture (HC) (58.7%) and polymerase chain reaction (PCR)
      (33.3%), in addition to higher mortality (2.9%). The PR isolates had higher
      values for PP (18.5 days) and Pmax (99.9*10(4)BT/mL) as well as higher positivity
      to FBE (87.2%), HC (100%), and PCR (83.3%). The correlations between the
      biological behaviour of the T. cruzi isolates and the clinical and
      epidemiological characteristics of Chagas disease are discussed.

PMID- 22406039
TI  - Effects of estrogenic compounds on neonatal oocyte development.
AB  - In the mouse, oocytes develop in germline cysts that undergo breakdown resulting
      in primordial follicles, consisting of a single oocyte surrounded by granulosa
      cells. During this process, approximately two-thirds of the oocytes die. Exposure
      of female mice to environmental estrogens can alter oocyte development, limiting
      the number of primordial follicles that can be used for reproduction. Here we
      asked whether exposure to synthetic estrogens, diethylstilbestrol, ethinyl
      estradiol and bisphenol A affected perinatal oocyte development. Neonatal mice
      were injected with a low or high dose of each compound on postnatal days (PND) 1
      4 and ovaries analyzed on PND5. Cyst breakdown, oocyte survival and follicle
      development were altered. The percentage of single oocyte was reduced from 84% in
      controls to 50-75%. The oocyte number per section was increased from 8 to 12-16.
      Follicle activation was reduced with 62% primordial follicles in controls to over
      80% in most cases.

PMID- 22406040
TI  - Simulation in echocardiography: an ever-expanding frontier.

PMID- 22406041
TI  - Failure of one-lung ventilation because of tracheobronchopathia osteoplastica
      during a heartport procedure with EZ-Blocker.

PMID- 22406042
TI  - Can the EuroSCORE predict midterm survival after aortic valve replacement?
AB  - OBJECTIVES: The EuroSCORE as a predictor for midterm survival after isolated
      aortic valve replacement (AVR) and combined AVR with coronary artery bypass graft
      (CABG) surgery was tested. Survival in different risk-stratification groups also
      was compared to the survival of the general Dutch population. DESIGN: A
      retrospective analysis of prospectively collected data. SETTING: A single-center
      study performed in an educational hospital. PARTICIPANTS: All patients (N =
      1,652) who underwent AVR with (n = 711) or without (n = 941) CABG surgery from
      January 2004 through December 2009. INTERVENTIONS: AVR with or without CABG
      surgery. MEASUREMENTS AND MAIN RESULTS: Univariate Cox regression analyses were
      used to identify the additive and the logistic EuroSCOREs as independent
      predictors of midterm mortality. Kaplan-Meier survival curves were used to
      compare the survival of different patients' risk subgroups, based on both the
      additive and the logistic EuroSCOREs, with the normal Dutch population matched
      for age and sex. Both additive and logistic EuroSCOREs were significant
      predictors of midterm mortality after isolated AVR and AVR with CABG surgery.
      This was also true for the different risk-stratification groups. Except for
      survival after AVR with CABG surgery in the high-risk group based on the additive
      EuroSCORE, no difference was found between survival after surgery and survival of
      the age- and sex-matched normal population. CONCLUSIONS: Both EuroSCORE models
      can predict midterm survival after isolated AVR and combined AVR with CABG
      surgery. However, the EuroSCORE is not a predictor for midterm survival when
      comparing the patient groups with the general Dutch population matched for age
      and sex. Except for high-risk patients undergoing AVR with CABG surgery, other
      risk subgroups have similar midterm survival to that of their age- and sex
      matched cohorts of the Dutch population.

PMID- 22406043
TI  - Low target sufentanil effect-site concentrations allow early extubation after
      valve surgery.
AB  - OBJECTIVES: To test the ability of low sufentanil effect-site concentrations (Ce)
      to shorten the time to tracheal extubation after valve surgery. DESIGN: A
      prospective, randomized, blinded, controlled study. SETTING: A single university
      hospital. PARTICIPANTS: Forty-eight patients scheduled for valve surgery under
      target-controlled propofol infusion. INTERVENTIONS: After ethical committee
      approval, patients were allocated randomly to receive sufentanil concentrations
      of 0.2, 0.3, or 0.4 ng/mL (n = 16 per group) during target-controlled propofol
      infusion. MEASUREMENTS AND MAIN RESULTS: Times to spontaneous eye opening, return
      of spontaneous breathing and extubation; number of changes and cumulative doses
      of propofol and sufentanil; incidences of light anesthesia and myocardial
      ischemia; intensive care unit and hospital stays; and costs of propofol,
      sufentanil, and ventilation were recorded. Compared with the sufentanil 0.4-ng/mL
      group, 0.2- and 0.3-ng/mL groups had shorter times to eye opening (24.8 min [SD
      7.8] and 52.6 min [12.5] v 85.6 min [10.0], respectively), spontaneous breathing
      (32.7 min [19.9] and 70.1 min [27.2] v 137.5 min [20.8], respectively), and
      extubation (112.2 min [16.9] and 161.9 min [32.9] v 271.3 min [27.4],
      respectively; p < 0.001), more frequent changes in propofol concentrations (p <
      0.001), higher cumulative propofol doses, lower cumulative sufentanil doses, and
      33% to 44% lower total cost (p < 0.001). Incidences of light anesthesia and
      myocardial ischemia and intensive care unit and hospital stays were similar for
      all groups. CONCLUSIONS: Compared with sufentanil Ce of 0.4 ng/mL, lower
      concentrations (0.2 and 0.3 ng/mL) promoted faster recovery and shorter times to
      extubation after valve surgery performed under target-controlled propofol
      infusion.

PMID- 22406044
TI  - Going with the flow: the dilemma of a laminar jet.

PMID- 22406045
TI  - Seasonal and spatial heterogeneity of recent sea surface temperature trends in
      the Caribbean Sea and southeast Gulf of Mexico.
AB  - Recent changes in ocean temperature have impacted marine ecosystem function
      globally. Nevertheless, the responses have depended upon the rate of change of
      temperature and the season when the changes occur, which are spatially variable.
      A rigorous statistical analysis of sea surface temperature observations over 25
      years was used to examine spatial variability in overall and seasonal temperature
      trends within the wider Caribbean. The basin has experienced high spatial
      variability in rates of change of temperature. Most of the warming has been due
      to increases in summer rather than winter temperatures. However, warming was
      faster in winter in the Loop Current area and the south-eastern Caribbean, where
      the annual temperature ranges have contracted. Waters off Florida, Cuba and the
      Bahamas had a tendency towards cooling in winter, increasing the amplitude of
      annual temperature ranges. These detailed patterns can be used to elucidate
      ecological responses to climatic change in the region.

PMID- 22406046
TI  - Determination of deployment specific chemical uptake rates for SPMD and PDMS
      using a passive flow monitor.
AB  - Passive sampling techniques facilitate the time-integrated measurement of
      pollutant concentrations through the use of a selective receiving phase. Accurate
      quantification using passive sampling devices rely on the implementation of
      methods that will negate the effects of environmental factors (flow, temperature,
      etc.) or that will allow the calculation of the chemical specific rates of uptake
      (R(s)) into the passive sampler employed. We have applied an in situ calibration
      technique based on the dissolution of gypsum to measure the average water
      velocity to which a sampler has been exposed. We demonstrate that the loss of
      gypsum from the passive flow monitor (PFM) can be applied to predict changes in
      R(s) dependent on flow when using the absorbent SPMD (semipermeable membrane
      device) and PDMS (polydimethyl siloxan) passive samplers. The application of the
      PFM will enhance the accuracy of measurements made when calculating and reporting
      environmental pollutant concentrations using a passive sampling device.

PMID- 22406047
TI  - Ad-KDRscFv:sTRAIL displays a synergistic antitumor effect without obvious
      cytotoxicity to normal tissues.
AB  - AIM: To investigate the antitumor activities and safety of Ad-KDRscFv, Ad-sTRAIL
      (114-281) and Ad-KDRscFv:sTRAIL in vivo and in vitro. METHODS: Recombinant
      replication-defective adenovirus vectors encoding either the extracellular domain
      (114-281 aa) of TRAIL, the KDRscFv (single chain antibody (scFv) against human
      vascular endothelial growth factor (VEGF) receptor KDR) or the fusion gene of
      KDRscFv:sTRAIL were constructed and transfected into HEK 293 cells for virus
      packaging. The recombinant virus particles were then infected human tumor cell
      lines of liver cancer (HepG2), gastric cancer (SGC-7901), colorectal cancer
      (SW480) and normal human liver cell line (LO2) to investigate the antitumor
      activities. Nude mice of the subcutaneous tumor models were established with
      HepG2 cells and were randomly divided into different groups to investigate the
      therapeutic effect and safety of these adenovirus particles on hepatocellular
      carcinoma. The expression of foreign proteins and the effect on microvascular
      number were also evaluated. RESULTS: All three adenovirus particles could induce
      apoptosis of cancer cells lines HepG2, SGC-7901 and SW480, but had no obvious
      lethal effect on LO2 cells. Ad-KDRscFv:sTRAIL showed the strongest tumoricidal
      effect. After intratumoral injection with these adenovirus particles on nude mice
      model, all the three adenoviruses could inhibit the tumor growth and
      angiogenesis, and the expression of foreign proteins (sTRAIL, KDRscFv and
      KDRscFv:sTRAIL fusion protein) was restricted to liver and tumor tissues. In
      coincidence with the result in vitro, Ad-KDRscFv:sTRAIL also had the strongest
      antitumor activity in vivo. No obvious pathological changes were detected in
      vivo. CONCLUSIONS: Replication-defective recombinant adenovirus of Ad-KDRscFv, Ad
      sTRAIL and Ad-KDRscFv:sTRAIL all had tumoricidal activities and Ad-KDRscFv:sTRAIL
      showed the strongest effect. All three adenoviruses had no obvious toxicity to
      normal cells and tissues in vitro and in vivo.

PMID- 22406048
TI  - Total glucosides of paeony induces regulatory CD4(+)CD25(+) T cells by increasing
      Foxp3 demethylation in lupus CD4(+) T cells.
AB  - Total glucosides of paeony (TGP), an active compound extracted from Paeony root,
      has been used in therapy for autoimmune diseases. However the molecular mechanism
      of TGP in the prevention of autoimmune response remains unclear. In this study,
      we found that TGP treatment significantly increased the percentage and number of
      Treg cells in lupus CD4(+) T cells. Further investigation revealed that treatment
      with TGP increased the expression of Foxp3 in lupus CD4(+) T cells by down
      regulating Foxp3 promoter methylation levels. However, we couldn't observe
      similar results in healthy control CD4(+) T cells treated by TGP. Moreover, our
      results also showed that IFN-gamma and IL-2 expression was enhanced in TGP
      treated lupus CD4(+) T cells. These findings indicate that TGP inhibits
      autoimmunity in SLE patients possibly by inducing Treg cell differentiation,
      which may in turn be due to its ability to regulate the methylation status of the
      Foxp3 promoter and activate IFN-gamma and IL-2 signaling.

PMID- 22406049
TI  - miR-137 is frequently down-regulated in glioblastoma and is a negative regulator
      of Cox-2.
AB  - MicroRNAs are strongly implicated in cancer but their specific roles and
      functions in the major cancers have yet to be fully elucidated. In this study, we
      defined the expression and function of miR-137, which we found to be
      downregulated in glioma samples and glioma cells by qRT-PCR. Ectopic expression
      of miR-137 in glioma cell lines inhibited proliferation and invasion. Using
      computational and expression analysis, Cox-2 was identified as a candidate target
      of miR-137. Reporter assay with 3'UTR of Cox-2 cloned downstream of the
      luciferase gene showed reduced luciferase activity in the presence of miR-137,
      providing strong evidence that miR-137 was a direct regulator of Cox-2.
      Expression analysis further revealed that Cox-2 was elevated in glioma and
      associated with survival of patients. Furthermore, we observed that Cox-2
      knockdown resulted in effects similar to those with miR-137 transfection in
      glioma cells. In conclusion, our study demonstrates that miR-137 deregulation is
      common in glioma, and restoration of its function inhibits cell proliferation and
      invasion, suggesting that miR-137 may act as a tumour suppressor.

PMID- 22406050
TI  - Prospective validation of a risk calculator which calculates the probability of a
      positive prostate biopsy in a contemporary clinical cohort.
AB  - BACKGROUND: Prediction models need validation to assess their value outside the
      development setting. OBJECTIVE: To assess the external validity of the European
      Randomised study of Screening for Prostate Cancer (ERSPC) Risk Calculator (RC) in
      a contemporary clinical cohort. METHODS: The RC calculates the probability of a
      positive sextant prostate biopsy (P(posb)) using serum prostate-specific antigen
      (PSA), results of digital rectal examination, transrectal ultrasound (TRUS) and
      ultrasound assessed prostate volume. We prospectively validated the RC in 320
      biopsied men (55-75 years), with no previous prostate biopsy, included in five
      Dutch hospitals in 2008-2011. If the P(posb) was >= 20% a biopsy was recommended.
      The performance of the RC was tested by comparing the observed outcomes to
      predicted probabilities, using the area under the curve (AUC) and decision curves
      analyses. RESULTS: Compared to the screening cohort, men in the clinical cohort
      differed. They had higher PSA levels (median 6.8 versus 4.3 ng/ml, p<0.01), less
      TRUS-lesions (27% versus 34%, p = 0.01) and more prostate cancer (PCa) at biopsy
      (43% versus 25%, p<0.01). Mainly eight biopsy cores were taken. Despite the
      differences between these cohorts, the mean observed probability agreed with the
      mean predicted probability (43% versus 40%). The RC predicted P(posb) better than
      a model with PSA and digital rectal examination, AUC 0.77 (95% confidence
      interval (CI) 0.72-0.83) and 0.71 (95%CI 0.65-0.76, p<0.01), respectively. This
      was confirmed by the decision curves analysis. Under the 20% threshold, 17%
      (11/63) of the biopsied men were diagnosed with PCa. Two of 11 men had an
      important cancer (Gleason 3+4). CONCLUSIONS: The ERSPC RC performs well in a
      Dutch clinical cohort in men with previous PSA tests and contemporary biopsy
      schemes, and outperforms a PSA and DRE-based approach in the decision to perform
      a biopsy.

PMID- 22406051
TI  - Calorie restriction prevents the development of insulin resistance and impaired
      insulin signaling in skeletal muscle of ovariectomized rats.
AB  - Insulin resistance of skeletal muscle glucose transport due to prolonged loss of
      ovarian function in ovariectomized (OVX) rats is accompanied by other features of
      the metabolic syndrome and may be confounded by increased calorie consumption. In
      this study, we investigated the role of calorie consumption in the development of
      insulin resistance in OVX rats. In addition, we examined the cellular mechanisms
      underlying skeletal muscle insulin resistance in OVX rats. Female Sprague-Dawley
      rats were ovariectomized (OVX) or sham-operated (SHAM). OVX rats either had free
      access to food, pair feeding (PF) with SHAM or received a 35% reduction in food
      intake (calorie restriction; CR) for 12weeks. Compared with SHAM, ovariectomy
      induced skeletal muscle insulin resistance, which was associated with decreases
      (32-70%) in tyrosine phosphorylation of the insulin receptor and insulin receptor
      substrate-1 (IRS-1), IRS-1 associated p85 subunit of phosphatidylinositol 3
      kinase (PI3-kinase), and Akt Ser(473) phosphorylation whereas insulin-stimulated
      phosphorylation of IRS-1 Ser(307), SAPK/JNK Thr(183)/Tyr(185), and p38 mitogen
      activated protein kinase (MAPK) Thr(180)/Tyr(182) was increased (24-62%). PF
      improved the serum lipid profile but did not restore insulin-stimulated glucose
      transport, indicating that insulin resistance in OVX rats is a consequence of
      ovarian hormone deprivation. In contrast, impaired insulin sensitivity and
      defective insulin signaling were not observed in the skeletal muscle of OVX+CR
      rats. Therefore, we provide evidence for the first time that CR effectively
      prevents the development of insulin resistance and impaired insulin signaling in
      the skeletal muscle of OVX rats.

PMID- 22406052
TI  - Comorbid depression and substance use disorder: longitudinal associations between
      symptoms in a controlled trial.
AB  - This study examined the longitudinal association between substance use and
      depressive symptoms in veterans receiving outpatient treatment for comorbid
      substance use disorder and major depression. Veterans (N = 237, mean age = 48.2
      years, 90% male, 70% Caucasian) received either 6 months of group integrated
      cognitive-behavioral therapy or twelve-step facilitation. Hamilton Depression
      Rating Scale scores and percent days using any substance were assessed every 3
      months up to 1 year posttreatment. Greater substance use predicted time-varying
      elevations in depression above individual patterns of change in depression.
      Moreover, change in depressive symptoms was associated with change in both the
      likelihood of any substance use and the frequency of use during the treatment and
      follow-up periods. Changes in these symptoms appear to be linked, such that
      individuals with greater reductions in substance use have greater reductions in
      depressive symptoms (and vice versa).

PMID- 22406053
TI  - Smoking family, secondhand smoke exposure at home, and nicotine addiction among
      adolescent smokers.
AB  - INTRODUCTION: Smoking family predicts adolescent smoking, but whether the level
      of nicotine addiction is affected by exposure to secondhand smoke (SHS) is
      unclear. We investigated the associations of smoking family and SHS exposure at
      home with morning smoking and heavier smoking among Chinese adolescent smokers.
      METHODS: In a school-based anonymous survey, 2182 adolescent smokers reported
      their smoking behaviors, smoking status of family members and peers, and SHS
      exposure at home and outside home in the past 7 days. Families with one or more
      smoking members (excluding the subject) were classified as smoking families and
      otherwise as non-smoking families. Smoking or wanting to smoke first thing in the
      morning (morning smoking), and consuming more cigarettes (heavier smoking)
      denoted higher levels of nicotine addiction. Regression analysis yielded adjusted
      odds ratios (AORs) for morning smoking and beta-coefficients for heavier smoking
      adjusting for potential confounders. RESULTS: Living with siblings and other co
      residing family members who smoked was significantly associated with morning
      smoking and heavier smoking. Compared with non-smoking families without SHS
      exposure at home, the AORs (95% CI) for morning smoking were 0.99 (0.76 to 1.29)
      for 0 day/week, 1.19 (0.95 to 1.50) for 1-3 days/week, 1.76 (1.41 to 2.21) for 4
      7 days/week (p for trend <0.001) and 1.50 (1.23 to 1.83) for any days/week of SHS
      exposure at home in smoking families. Similarly, 4-6 days/week of SHS exposure at
      home significantly predicted heavier smoking. CONCLUSION: Living with smoking
      family members and SHS exposure at home are associated with nicotine addiction in
      Chinese adolescent smokers.

PMID- 22406054
TI  - Stay focussed - muffle that resonant bass!
AB  - Increased rhythmic brain activity in the high frequency range and decreased
      rhythmic activity in the low frequency range is a hallmark of cognitive function
      and ability. A novel study links these findings to the cholinergic theory of
      attention, demonstrating that attention-induced rebalancing of brain rhythms is
      augmented by acetylcholine.

PMID- 22406055
TI  - Percutaneous left ventricular support for high-risk PCI and cardiogenic shock:
      who gets what?
AB  - BACKGROUND: Temporary use of a percutaneous left ventricular assist device
      (PLVAD) may be beneficial in patients undergoing high-risk percutaneous coronary
      intervention (PCI) and those with cardiogenic shock (CS). METHODS: Seventy-four
      consecutive patients undergoing high-risk PCI and those with CS receiving
      intraaortic balloon pump (IABP), TandemHeart (TH), or Impella device (IMP) were
      enrolled. Patient undergoing high-risk PCI (n=57) and those treated for CS (n=17)
      were analyzed as separate cohorts. Patients undergoing IABP-assisted PCI were
      compared to those undergoing PLVAD (TH and IMP)-assisted PCI. The primary end
      point was in-hospital major adverse cardiovascular events, and the secondary end
      point was in-hospital vascular complications. RESULTS: For the high-risk PCI
      cohort (n=57), 22 received PLVAD and 35 received IABP. Patients receiving IABP
      were younger and less likely to have a prior myocardial infarction (MI) and less
      likely to be on dialysis compared to those receiving PLVAD support. Patients
      receiving PLVAD support had a higher baseline Syntax score, had a higher
      prevalence of unprotected left main disease, underwent treatment of more coronary
      lesions, received more coronary stents, and more likely received drug-eluting
      stents compared to those receiving IABP support. The primary and secondary end
      points were similar between both groups. For the CS cohort (n=17), 4 received
      PLVAD and 13 received IABP. Patients receiving PLVAD support were more likely to
      have a prior MI, had a lower ejection fraction, underwent treatment of more
      coronary lesions, and received more coronary stents compared to those receiving
      IABP support. The primary and secondary end points were similar between both
      groups. CONCLUSIONS: IABP compared with PLVAD use for high-risk PCI and CS is
      associated with significantly different baseline patient, clinical, procedural,
      and angiographic characteristics. In-hospital clinical outcome was similar
      between both groups in both the high-risk PCI and the CS cohorts. When physicians
      have access to each of these devices, short-term clinical outcome appears to be
      similar.

PMID- 22406057
TI  - Embolic myocardial infarction diagnosed with Fourier domain optical coherence
      tomography.
AB  - We report the case of a young female with embolic myocardial infarction. The
      embolic etiology was confirmed by Fourier Domain Optical Coherence Tomography as
      well as histo-pathology.

PMID- 22406056
TI  - Intravascular ultrasound insights from the Cobalt Chromium Stent With
      Antiproliferative for Restenosis II (COSTAR II) trial comparing CoStar and Taxus
      paclitaxel-eluting stents.
AB  - BACKGROUND: Dedicated IVUS analyses of the second CObalt chromium STent with
      Antiproliferative for Restenosis (COSTAR II) trial have not been documented. We
      aim to compare IVUS findings between CoStar paclitaxel-eluting stent (PES) and
      Taxus PES in patients enrolled in the COSTAR II trial. We also attempted to
      examine the possible regional impact of multiple stenting. METHODS AND MATERIALS:
      Among the 1700 patients enrolled, 238 were assigned to an IVUS cohort including
      168 patients treated by provisional multiple stenting. At 9 months, qualitative
      and quantitative IVUS observations including incomplete stent apposition (ISA)
      and neointimal proliferation (neointimal obstruction: neointimal volume/stent
      volume *100) were compared between CoStar and Taxus PESs. RESULTS: In qualitative
      analysis, late-acquired ISA was observed in 1 patient treated by Taxus PES.
      Impaired strut continuity suggestive of stent fracture was observed in 2 out of
      33 patients treated by multiple CoStar, and 4 out of 21 patients treated by
      multiple Taxus (P=.14). No such findings were found in single-stented patients in
      either stent subset. Quantitative analysis showed greater neointimal obstruction
      in CoStar (19.7%+/-13.4%, n=52) than in Taxus (10.7%+/-9.9%, n=38), whereas no
      significant difference in neointimal obstruction was found between single and
      multiple stenting in either CoStar or Taxus PES. CONCLUSIONS: The CoStar PES
      exhibits greater neointimal proliferation compared with Taxus PES at 9 months but
      with similar qualitative outcomes including late-acquired ISA. IVUS findings
      suggestive of stent fracture were found only in multiple-stenting cases
      irrespective of the stent used.

PMID- 22406058
TI  - Inappropriate use of risk score models for operative mortality in nonsurgical
      treatments.

PMID- 22406059
TI  - A prospective multicenter registry of laser therapy for degenerated saphenous
      vein graft stenosis: the COronary graft Results following Atherectomy with Laser
      (CORAL) trial.
AB  - PURPOSE: The primary aim of this study was to prospectively evaluate the safety
      and efficacy of Excimer laser atherectomy as a primary treatment strategy in
      consecutively eligible patients presenting for percutaneous coronary intervention
      (PCI) of degenerated saphenous vein graft (SVG) lesions using a multicenter
      registry. Prior single-center experience suggested that laser atherectomy may
      decrease acute procedural complications during treatment of degenerated SVGs,
      including lesions not amenable to distal protection devices (DPDs). METHODS AND
      MATERIALS: The COronary graft Results following Atherectomy with Laser
      investigators enrolled 98 patients at 18 centers between June 23, 2003, and
      October 4, 2004, with greater than 50% stenosis of an SVG who presented for PCI
      due to angina pectoris or objective evidence of myocardial ischemia in a
      concordant myocardial distribution. Laser atherectomy was planned. Patients were
      excluded if the operator planned to utilize a DPD. Inclusion and exclusion
      criteria were aligned to those in the Saphenous vein graft Angioplasty Free of
      Emboli Randomized (SAFER) trial. RESULTS: The primary end point [30-day major
      adverse cardiac events (MACE)] occurred in 18/98 (18.4%) patients driven
      primarily by non-q-wave myocardial infarction. Major procedural complications
      included no reflow (n=5) and major dissection (n=1). No perforations occurred.
      Univariate predictors of 30-day MACE included lesion length, vessel angulation,
      plaque burden, SVG degeneracy score, number of laser pulses used, and larger
      sized laser catheters. CONCLUSIONS: This study demonstrated that Excimer laser
      atherectomy of diseased SVGs is feasible with results comparable to the 30-day
      MACE in the control population from the SAFER trial. Whether the addition of
      laser to embolic protection devices is of any clinical utility remains to be
      tested in future studies.

PMID- 22406060
TI  - Independence of measles-specific humoral and cellular immune responses to
      vaccination.
AB  - With a larger, independent cohort and more sophisticated measures, we sought to
      confirm our work that indicated independence of humoral and cellular immunity
      following measles vaccination. We recruited an age-stratified random cohort of
      764 healthy subjects from all socioeconomic strata, all with medical-record
      documentation of 2 age-appropriate doses of measles-containing vaccine. We
      quantified measles-specific neutralizing antibody levels and assayed the
      interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assay (ELISPOT)
      response to measles virus. We also measured secreted cytokines from the
      peripheral blood mononuclear cells (PBMCs) in response to measles virus by
      performing enzyme-linked immunosorbent assays as secondary measures of cellular
      immune status. The median antibody level and median IFN-gamma ELISPOT response
      were 844 mIU/mL (interquartile range [IQR]: 418-1,752) and 36 (IQR: 13.00-69.00)
      spot-forming cells (per 2 * 10(5) PBMCs), respectively. We observed only a very
      weak and negative correlation (Spearman's r(s) or rho of -0.090 [95% confidence
      interval: -0.162--0.018]). We observed a similar lack of quantitatively important
      correlations between the neutralizing antibody level and any of the secondary
      measures. Our data confirm the independence of humoral and cellular immune
      responses after the second dose of measles vaccination. As researchers pursue
      novel measles vaccine and measles vaccine delivery systems, they must not infer
      that humoral responses predict cellular responses.

PMID- 22406062
TI  - [Inhibition of Staphylococcus epidermidis adhesion on titanium surface with
      bioactive water-soluble copolymers bearing sulfonate, phosphate or carboxylate
      functions].
AB  - Implanted prostheses are sometimes subject to bacterial infections, which can
      threat their benefit rule on a long-term basis. Various methods are studied to
      fight against these infections. Among them, the grafting of bioactive polymers
      onto the prosthesis surface shows up as a promising way to the problem of
      infections. This work presents the influence of various water-soluble bioactive
      polymers on the inhibition of the Staphylococcus epidermidis adhesion on the
      titanium samples surfaces initially preadsorbed with various proteins. Whatever
      the studied protein is, it is shown that the bioactive polymer containing
      sulfonate functions generates an inhibition of the adhesion of Staphylococcus
      epidermidis. For a plasma preadsorption, the inhibition rate rises up to 68% when
      the concentration of sulfonate function is 2.5MUmol/L. Titanium surfaces grafted
      with the bioactive polymer were also tested. We find an inhibitive activity of
      the adhesion close to that of the previous case. These preliminary results can
      point up a clinical interest in the fight against the medical devices infection,
      because they highlight a clear local effect of S. epidermidis adhesion
      inhibition. Copolymers containing other functional groups (phosphate or
      carboxylate) were dissolved in a bacterial suspension to monitor the influence of
      the composition on the adhesion inhibition. Their inhibition rates are not
      significantly lower than those of pNaSS homopolymers, as much as the sulfonate
      function proportion remains higher than 50%. Thus, the sulfonate function is the
      main responsible for the inhibition of the S. epidermidis adhesion.

PMID- 22406061
TI  - A pro-inflammatory role of deubiquitinating enzyme cylindromatosis (CYLD) in
      vascular smooth muscle cells.
AB  - CYLD, a deubiquitinating enzyme (DUB), is a critical regulator of diverse
      cellular processes, ranging from proliferation and differentiation to
      inflammatory responses, via regulating multiple key signaling cascades such as
      nuclear factor kappa B (NF-kappaB) pathway. CYLD has been shown to inhibit
      vascular lesion formation presumably through suppressing NF-kappaB activity in
      vascular cells. However, herein we report a novel role of CYLD in mediating pro
      inflammatory responses in vascular smooth muscle cells (VSMCs) via a mechanism
      independent of NF-kappaB activity. Adenoviral knockdown of Cyld inhibited basal
      and the tumor necrosis factor alpha (TNFalpha)-induced mRNA expression of pro
      inflammatory cytokines including monocyte chemotactic protein-1 (Mcp-1),
      intercellular adhesion molecule (Icam-1) and interleukin-6 (Il-6) in rat adult
      aortic SMCs (RASMCs). The CYLD deficiency led to increases in the basal NF-kappaB
      transcriptional activity in RASMCs; however, did not affect the TNFalpha-induced
      NF-kappaB activity. Intriguingly, the TNFalpha-induced IkappaB phosphorylation
      was enhanced in the CYLD deficient RASMCs. While knocking down of Cyld decreased
      slightly the basal expression levels of IkappaBalpha and IkappaBbeta proteins, it
      did not alter the kinetics of TNFalpha-induced IkappaB protein degradation in
      RASMCs. These results indicate that CYLD suppresses the basal NF-kappaB activity
      and TNFalpha-induced IkappaB kinase activation without affecting TNFalpha-induced
      NF-kappaB activity in VSMCs. In addition, knocking down of Cyld suppressed
      TNFalpha-induced activation of mitogen activated protein kinases (MAPKs)
      including extracellular signal-activated kinases (ERK), c-Jun N-terminal kinase
      (JNK), and p38 in RASMCs. TNFalpha-induced RASMC migration and monocyte adhesion
      to RASMCs were inhibited by the Cyld knockdown. Finally, immunochemical staining
      revealed a dramatic augment of CYLD expression in the injured coronary artery
      with neointimal hyperplasia. Taken together, our results uncover an unexpected
      role of CYLD in promoting inflammatory responses in VSMCs via a mechanism
      involving MAPK activation but independent of NF-kappaB activity, contributing to
      the pathogenesis of vascular disease.

PMID- 22406063
TI  - Kinetic study of acid-catalyzed cellulose hydrolysis in 1-butyl-3
      methylimidazolium chloride.
AB  - In this paper, the kinetics of acid-catalyzed cellulose hydrolysis in ionic
      liquids (ILs) was investigated by using 1-butyl-3-methylimidazolium chloride
      ([Bmim]Cl) as the model IL. General kinetic equations for the formation of
      glucose as well as cellooligomers were constructed at a molecular level, assuming
      that cellulose is fully dissolved to form a homogenous solution and that the
      scission of the glycosidic bond occurs randomly within the cellulose chain.
      Experimental data were well fitted according to these equations. Variations of
      kinetic parameters in the presence of different water content indicated that
      water behaved also as a base to decrease the acidity of the reaction medium. More
      importantly, it offered a profile of the evolution of cellooligomers. These
      results provided insights into the detailed mechanisms of cellulose hydrolysis in
      a non-aqueous, homogenous environment and should be valuable for developing
      strategies to depolymerize lignocellulosic biomass.

PMID- 22406064
TI  - Multiple chitinases of an endophytic Serratia proteamaculans 568 generate chitin
      oligomers.
AB  - Serratia proteamaculans 568 genome revealed the presence of four family 18
      chitinases (Sp ChiA, Sp ChiB, Sp ChiC, and Sp ChiD). Heterologous expression and
      characterization of Sp ChiA, Sp ChiB, and Sp ChiC showed that these enzymes were
      optimally active at pH 6.0-7.0, and 40 degrees C. The three Sp chitinases
      displayed highest activity/binding to beta-chitin and showed broad range of
      substrate specificities, and released dimer as major end product from oligomeric
      and polymeric substrates. Longer incubation was required for hydrolysis of trimer
      for the three Sp chitinases. The three Sp chitinases released up to tetramers
      from colloidal chitin substrate. Sp ChiA and Sp ChiB were processive chitinases,
      while Sp ChiC was a non-processive chitinase. Based on the known structures of
      ChiA and ChiB from S. marcescens, 3D models of Sp ChiA and Sp ChiB were
      generated.

PMID- 22406065
TI  - Sequential heterotrophy-dilution-photoinduction cultivation for efficient
      microalgal biomass and lipid production.
AB  - A novel cultivation strategy called "sequential heterotrophy-dilution
      photoinduction" was developed for efficient algal biomass and lipid production.
      Three Chlorella species were first cultivated heterotrophically to achieve high
      cell density, then the broth was diluted to suitable concentration (2-5 g/L) and
      transferred to light environment for photoinduction. With this strategy, the
      Chlorella intracellular protein and chlorophyll increased rapidly to 50.87% and
      32.97 mg/g by a 12-h illumination, which were close to the level of cells
      cultivated photoautotrophically. Moreover, the lipid contents were increased by
      84.57%, 70.65% and 121.59% within 24-h photoinduction for C. vulgaris, C.
      pyrenoidosa and C. ellipsoidea, respectively. Maximum lipid content as 26.11% of
      biomass and maximum lipid productivity of 89.89 mg/L/d was both accomplished by
      C. pyrenoidosa. Further outdoor experiments showed consistent patterns.
      Therefore, the proposed strategy provided an effective approach for microalgal
      biomass production to meet the urgent need for both health food and biodiesel.

PMID- 22406066
TI  - Improving the productivity of propionic acid with FBB-immobilized cells of an
      adapted acid-tolerant Propionibacterium acidipropionici.
AB  - Propionic acid is an important short-chain fatty acid with many applications, but
      its large-scale bioproduction was hindered by the low productivity. An adapted
      acid-tolerant Propionibacterium acidipropionici CGMCC 1.2230 strain was selected
      to produce propionic acid with a relatively high productivity (0.29 g/(Lh)) in
      the free-cell fermentation. Further immobilized-cell fermentation in fibrous-bed
      bioreactor (FBB) supported high-level repeated batch fermentations with a high
      productivity of 0.96 g/(Lh). The FBB also presents the potential to increase
      final propionic acid concentration by using glucose feeding strategy. The
      propionic acid concentration was increased to 51.2g/L in the fed-batch
      fermentation with the productivity of 0.71 g/(Lh). By adopting the above
      strategies, sugarcane bagasse hydrolysate could support the production of
      propionic acid with high productivity in the repeat-batch and fed-batch
      fermentations. The present work would pave one road to the accomplishment of
      large-scale bioproduction of propionic acid from renewable resources.

PMID- 22406067
TI  - The contribution of situational probability information to anticipatory skill.
AB  - OBJECTIVES: To determine the contribution of situational probability information
      to the anticipatory responses of skilled tennis players representative of two
      different stages of development. DESIGN: Participants were required to predict
      the location of tennis serves presented to them on a plasma touchscreen from the
      perspective of the receiver. METHODS: Serves were sequenced into a series of
      games and sets with a score presented before each point, typical of a game of
      tennis. The game score was manipulated to provide advance probability
      information. The location of the serve for the first point of each game was
      always directed to the same location. A total of 12 service games consisting of
      96 points were presented with interest in whether players would detect the
      relationship between the game score and resultant serve location. RESULTS: A 2*12
      (age*service game) ANOVA with repeated measures on the second factor revealed a
      significant age by service game interaction for response time (F11,297=3.86,
      p<0.05, eta(p)2=.12). The older players picked up the occurrence of the first
      point service pattern after the ninth service game whereas the younger, players
      did not. There were no significant response accuracy differences between the
      groups in relation to the first point. CONCLUSIONS: The findings highlight the
      important role of situational probability information, in addition to movement
      kinematics, for successful anticipatory performance and suggest that the pick-up
      of such information is not utilised by younger players.

PMID- 22406068
TI  - Brain activation to cues predicting inescapable delay in adolescent Attention
      Deficit/Hyperactivity Disorder: an fMRI pilot study.
AB  - BACKGROUND: The choice of small immediate over large delayed rewards (i.e.,
      impulsive choice) is a signal marker of motivational style in Attention
      Deficit/Hyperactivity Disorder (ADHD). The delay aversion model proposes that, in
      part, this is a conditioned delay avoidance response. Here we test the prediction
      derived from this model that, in ADHD, cues predicting inescapable delay
      differentially activate brain regions shown previously to be responsive to
      motivationally salient, negatively valenced environmental events. METHODS: Ten
      adolescents with ADHD and 10 age matched controls performed a simple speeded
      reaction time task under two conditions. On Escape Delay trials slow responses
      only were punished by the imposition of post-response delay periods. On No Escape
      Delay trials post-response delay occurred on all trials irrespective of response
      speed. Using functional Magnetic Resonance Imaging (fMRI) BOLD responses were
      acquired to compare anticipatory brain activation following the two cue types.
      ROI analyses found significant ADHD-related hyperactivation following No Escape
      compared to Escape Delay trial cues in the insula, amygdala, ventral striatum and
      orbito-frontal cortex. CONCLUSION: The results of this pilot study provide
      further evidence for the role of altered motivational systems in ADHD and the
      most direct evidence for a biological basis of delay aversion.

PMID- 22406069
TI  - Role of selected mutations in the Q/N rich region of TDP-43 in EGFP-12xQ/N
      induced aggregate formation.
AB  - The overview of TDP 43 functions immediately disclose a number of open questions
      regarding its pathological role. The formation of TDP-43 aggregates is one of the
      major distinguishing features of TDP-43 proteinopathies, especially in patients
      affected by Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar
      degeneration (FTLD). At the moment, however, very little is known regarding the
      biological processes that underlie TDP-43 aggregation and, most importantly, its
      potential consequences on cellular metabolism. For these reasons, it is
      particularly important to further investigate this process in order to gain a
      better understanding of the pathology and to develop novel therapeutic effectors.
      In this report, we focus on a series of missense mutations associated with
      disease in the 342-366 region of this protein to examine their ability to affect
      RNA splicing regulation and to induce aggregate formation. In particular,
      aggregate formation was assessed in a novel system capable of inducing TDP-43
      aggregation in experimental cell lines and primary neuronal cultures. The results
      of this analysis showed that the presence of two of these missense mutations in
      the 342-366 region (G348V and N352S) could differentially affect the levels and
      appearance of TDP-43 aggregation with respect to the wild-type protein. This
      article is part of a Special Issue entitled RNA-Binding Proteins.

PMID- 22406070
TI  - Performance based objective outcome measures and spinal manipulation.
AB  - This paper provides a general overview of performance based outcome measures used
      in an attempt to objectively measure the ramifications of spinal manipulation.
      While not a systematic or exhaustive review it serves to categorize, and provide
      insight into the background, successes and shortcomings of measurement techniques
      used. The outcome measures are drawn from the full spectrum of approaches to
      research and are broken down into the following sections: (1) biomechanically
      constrained motor performance measures, (2) neurologically constrained
      performance measures and (3) perceptual, perceptual motor, and complex task
      constrained performance measures. The paper concludes with some future research
      directions to enhance the understanding of the impact of spinal manipulation, and
      how to objectively measure its mechanical and physiological effects on the human
      system.

PMID- 22406071
TI  - Unique components of the plant mitochondrial protein import apparatus.
AB  - The basic mitochondrial protein import apparatus was established in the earliest
      eukaryotes. Over the subsequent course of evolution and the divergence of the
      plant, animal and fungal lineages, this basic import apparatus has been modified
      and expanded in order to meet the specific needs of protein import in each
      kingdom. In the plant kingdom, the arrival of the plastid complicated the process
      of protein trafficking and is thought to have given rise to the evolution of a
      number of unique components that allow specific and efficient targeting of
      mitochondrial proteins from their site of synthesis in the cytosol, to their
      final location in the organelle. This includes the evolution of two unique outer
      membrane import receptors, plant Translocase of outer membrane 20 kDa subunit
      (TOM20) and Outer membrane protein of 64 kDa (OM64), the loss of a receptor
      domain from an ancestral import component, Translocase of outer membrane 22 kDa
      subunit (TOM22), evolution of unique features in the disulfide relay system of
      the inter membrane space, and the addition of an extra membrane spanning domain
      to another ancestral component of the inner membrane, Translocase of inner
      membrane 17 kDa subunit (TIM17). Notably, many of these components are encoded by
      multi-gene families and exhibit differential sub-cellular localisation and
      functional specialisation. This article is part of a Special Issue entitled:
      Protein Import and Quality Control in Mitochondria and Plastids.

PMID- 22406072
TI  - Mitochondrial morphology in mitophagy and macroautophagy.
AB  - Mitochondria are critical organelles in energy conversion, metabolism and
      amplification of signalling. They are however also major sources of reactive
      oxygen species and when dysfunctional they consume cytosolic ATP. Maintenance of
      a cohort of healthy mitochondria is therefore crucial for the overall cell
      fitness. Superfluous or damaged organelles are mainly degraded by mitophagy, a
      selective process of autophagy. In response to the triggers of mitophagy,
      mitochondria fragment: this morphological change accompanies the exposure of "eat
      me" signals, resulting in the engulfment of the organelle by the autophagosomes.
      Conversely, during macroautophagy mitochondria fuse to be spared from degradation
      and to sustain ATP production in times of limited nutrient availability. Thus,
      mitochondrial shape defines different types of autophagy, highlighting the
      interplay between morphology of the organelle and complex cellular responses.
      This article is part of a Special Issue entitled: Mitochondrial dynamics and
      physiology.

PMID- 22406073
TI  - Role of lbx2 in the noncanonical Wnt signaling pathway for convergence and
      extension movements and hypaxial myogenesis in zebrafish.
AB  - It has been suggested that mouse lbx1 is essential for directing hypaxial
      myogenic precursor cell migration. In zebrafish, the expression of lbx1a, lbx1b,
      and lbx2 has been observed in pectoral fin buds. It has also been shown that
      knocking down endogenous lbx2 in zebrafish embryos diminishes myoD expression in
      the pectoral fin bud. However, downstream lbxs signals remain largely unexplored.
      Here, we describe a previously unknown function of zebrafish lbx2 (lbx2) during
      convergent extension (CE) movements. The abrogation of the lbx2 function by two
      non-overlapping morpholino oligonucleotides (MOs) resulted in the defective
      convergence and extension movements in morphants during gastrulation. Our
      transplantation studies further demonstrated that the overexpression of lbx2
      autonomously promotes CE movements. Expression of wnt5b is significantly reduced
      in lbx2 morphants. We have demonstrated that application of the wnt5b MO, a
      dominant-negative form of disheveled (Dvl) and a chemical inhibitor of Rho
      associated kinase Y27632 in zebrafish embryos have effects reminiscent that are
      of the CE and hypaxial myogenesis defects observed in lbx2 morphants. Moreover,
      the CE and hypaxial mesoderm defects seen in lbx2 morphants can be rescued by co
      injection with wnt5b or RhoA mRNA. However, this reduced level of active RhoA and
      hypaxial myogenesis defects in the embryos injected with the dominant-negative
      form of Dvl mRNA cannot be effectively restored by co-injection with lbx2 mRNA.
      Our results suggest that the key noncanonical Wnt signaling components Wnt5, Dvl,
      and RhoA are downstream effectors involved in the regulative roles of lbx2 in CE
      movement and hypaxial myogenesis during zebrafish embryogenesis.

PMID- 22406074
TI  - What is the best method of proteinuria measurement in clinical trials of
      endothelin receptor antagonists?
AB  - AIMS: To determine whether protein-creatinine ratio (PCR) and albumin-creatinine
      ratio (ACR) are comparable to 24h urine protein in terms of agreement and
      repeatability, and therefore whether they are suitable for monitoring and
      comparing reduction in proteinuria in clinical trials of endothelin receptor
      antagonists. MAIN METHODS: Using data from a recent study of sitaxentan in 27
      patients with proteinuric chronic kidney disease, the assays were compared with
      reference to their agreement, repeatability, the number of measurements required
      to obtain accurate results and correlation with reduction in proteinuria at
      baseline. KEY FINDINGS: The median coefficient of variation was lower for PCR
      than 24h urine protein (25 vs. 28%) but the range was higher (70 vs. 47%). When
      converted into the same units, mean difference between 24h urine protein and both
      PCR (0.03 g/day), and ACR (0.10 g/day), was small. However, scatter increased
      with mean level of proteinuria, such that agreement fell substantially above 1.5
      g/day. According to 2-factor within-subjects ANOVA, the assay used was not a
      significant source of variation (PCR p=0.63, ACR p=0.38). With 3 measurements at
      each time point, baseline proteinuria correlated equally well with change in
      proteinuria, and percentage change was detected accurately by all 3 methods.
      SIGNIFICANCE: PCR and ACR may well be suitable replacements for 24h urine protein
      in the clinical trial context due to their similar accuracy and repeatability,
      greater convenience and lower cost. However, a randomised control trial comparing
      all 3 assays in a larger and more diverse population is necessary before 24h
      urine protein can be replaced.

PMID- 22406075
TI  - Association of single nucleotide polymorphisms of nicotinic acetylcholine
      receptor subunits with cervical neoplasia.
AB  - AIMS: Cholinergic signaling, particularly in response to non-physiological
      ligands like nicotine, stimulates carcinogenesis of a variety of tissue types
      including epithelia of the cervix uteri. Cholinergic signaling is mediated by
      nicotinic acetylcholine receptors (nAChRs), which are pentamers formed by subsets
      of 16 nAChR subunits. Recent literature suggests that single nucleotide
      polymorphisms (SNPs) of some of these subunits, notably alpha5, are risk factors
      for developing lung cancer in smokers as well as in non-smokers. MAIN METHODS: We
      have studied the prevalence of four SNPs in the alpha5, alpha9, and beta1
      subunits, which are expressed in cervical cells, in 456 patients with cervical
      cancers, precursor lesions, and healthy controls from two cohorts in Mexico. KEY
      FINDINGS: A SNP in the alpha9 subunit, the G allele of rs10009228 (alpha9, A>G)
      shows a significant trend in the combined cohort, indicating that this allele
      constitutes a risk factor for neoplastic progression. The A allele of the SNP
      rs16969968 (alpha5, G>A), which correlates with the development of lung cancer,
      shows a non-significant trend to be associated with cervical lesions. Two other
      SNPs, rs55633891 (alpha9, C>T) and rs17856697 (beta1, A>G), did not exhibit a
      significant trend. SIGNIFICANCE: Our study points to a potential risk factor of
      cervical carcinogenesis with importance for DNA diagnosis and as a target for
      intervention.

PMID- 22406076
TI  - Endothelin B receptor is not required but necessary for finite regulation of
      ovulation.
AB  - AIMS: In the ovary, endothelins regulate a variety of ovarian functions that
      include but not limited to folliculogenesis, steroidogenesis, oocyte maturation,
      ovulation and corpus luteum (CL) function. Two cognate receptors, EDNRA and EDNRB
      are constitutively expressed in the ovary, and mediate the regulatory endothelin
      actions. However, the physiological significance of the presence of the two
      receptors that often elicit opposite responses upon activation by an endothelin
      is yet to be determined. This study was proposed to test the hypothesis that both
      receptors are present in the ovary to lend an endothelin a finite regulation of
      ovulation. MAIN METHODS: A rescued EDNRB knockout (rEDNRB-KO) mouse that is
      deficient of EDNRB expression in all cells but adrenergic cell lineage was used
      to test the impact of the loss of function of EDNRB on ovulation. The EDNRB gene
      deletion and its confirmation at mRNA level were assessed by molecular biology
      techniques, and the number and size of corpus lutea was determined by ovarian
      histology. KEY FINDINGS: Female rEDNRB-KO mice had larger litter sizes (numbers
      of pups per birth) and their ovaries contained more corpora lutea than wild type
      littermates. SIGNIFICANCE: This result shows that without EDNRB excessive
      ovulation occurs, suggesting a role of EDNRB in having the extent of ovulation
      confined.

PMID- 22406077
TI  - Endothelin receptor antagonist has limited access to the fetal compartment during
      chronic maternal administration late in pregnancy.
AB  - AIMS: Endothelin receptor A (ET(A)) antagonism normalizes fetal growth in several
      models of rodent fetal growth restriction (FGR). Our aims were to determine the
      levels of ET(A) antagonist in maternal and fetal plasma following chronic
      maternal administration, and to determine its impact on pregnancy outcome,
      survival and growth of rat pups. MAIN METHODS: Timed pregnant rats were treated
      with one of two endothelin receptor antagonists or vehicle, from gestation day 14
      21 (term=22 days). The antagonists and their respective doses were ABT-546
      (20mg/kg/day) and FR139317 (12 mg/kg/day). On day 21, in six rats per group,
      maternal and fetal plasma ABT-546 was assayed by HPLC. Five additional rats in
      each group delivered spontaneously and nursed their pups through postpartum day
      7. Viability of newborns, oxygen saturation, litter sizes, and pup weights were
      recorded on postpartum days 1 and 7. KEY FINDINGS: Fetal antagonist levels
      reached only 2% of maternal levels (p<0.01). There were no significant
      differences among groups in length of gestation; litter size; survival, number
      and weight of live pups at birth and at 7 days postpartum; and tissue oxygen
      saturation. SIGNIFICANCE: Maternal administration of an ET(A) antagonist, at a
      dose sufficient to ameliorate FGR, has no adverse impact on survival and growth
      of neonatal rat pups. ET(A) antagonism, delivered maternally, produces
      sufficiently low fetal plasma levels of antagonist so as not to present a
      survival threat to the neonatal pups. The beneficial effects of maternally
      administered ET(A) antagonism on fetal growth occur in the maternal, not the
      fetal, compartment.

PMID- 22406078
TI  - Neural differentiation of umbilical cord mesenchymal stem cells by sub-sonic
      vibration.
AB  - AIMS: Adult stem cells, such as umbilical cord-derived mesenchymal stem cells (UC
      MSCs), have the potential to differentiate into various types of cells, including
      neurons. Research has shown that mechanical stimulation induces a response in
      MSCs, specifically, low and high intensity sub-sonic vibration (SSV) has been
      shown to facilitate wound healing. In this study, the effects of SSV were
      examined by assessing the proliferation and differentiation properties of MSCs.
      MAIN METHODS: hUC-MSCs were isolated from Wharton's jelly, including the smooth
      muscle layer of the umbilical cord. During subculture, the cells were passaged
      every 5-6 days using nonhematopoietic stem cell media. To measure the effect of
      sonic vibration, SSV was applied to these cells continuously for 5 days. KEY
      FINDINGS: In this study, the morphology of hUC-MSCs was altered to resemble
      neurons by SSV. Further, the mRNA and protein levels of neuron-specific markers,
      including MAP2, NF-L, and NeuroD1, increased. In addition, other neural cell
      markers, such as GFAP and O4, were increased. These results suggest that hUC-MSCs
      differentiated into neural cells upon SSV nonselectively. In a mechanism study,
      the ERK level increased in a time-dependent manner upon SSV for 12 h.
      SIGNIFICANCE: The results of this study suggest that SSV caused hUC-MSCs to
      differentiate into neural cells via ERK activation.

PMID- 22406079
TI  - Characterization of A-935142, a hERG enhancer, in the presence and absence of
      standard hERG blockers.
AB  - AIMS: In a previous study we found that A-935142 enhanced hERG current in a
      concentration-dependent manner by facilitating activation, reducing inactivation,
      and slowing deactivation (Su et al., 2009). A-935142 also shortened action
      potential duration (APD90) in canine Purkinje fibers and guinea pig atrial
      tissue. This study focused on the combined effects of the prototypical hERG
      enhancer, A-935142 and two hERG current blockers (sotalol and terfenadine). MAIN
      METHODS: The whole-cell voltage clamp method with HEK 293 cells heterologously
      expressing the hERG channel (Kv 11.1) was used. KEY FINDINGS: A-935142 did not
      compete with 3H-dofetilide binding, suggesting that A-935142 does not overlap the
      binding site of typical hERG blockers. In whole-cell voltage clamp studies we
      found: 1) 60 MUM A-935142 enhanced hERG current in the presence of 150 MUM
      sotalol (57.5+/-5.8%) to a similar extent as seen with A-935142 alone (55.6+/
      5.1%); 2) 150 MUM sotalol blocked hERG current in the presence of 60 MUM A-935142
      (43.5+/-1.5%) to a similar extent as that seen with sotalol alone (42.0+/-3.2%)
      and 3) during co-application, hERG current enhancement was followed by current
      blockade. Similar results were obtained with 60 nM terfenadine combined with A
      935142. SIGNIFICANCE: These results suggest that the hERG enhancer, A-935142 does
      not compete with these two known hERG blockers at their binding site within the
      hERG channel. This selective hERG current enhancement may be useful as a
      treatment for inherited or acquired LQTS (Casis et al., 2006).

PMID- 22406080
TI  - Endothelin-1 plasma levels and vascular endothelial dysfunction in primary open
      angle glaucoma.
AB  - AIMS: To assess the relationship between endothelial dysfunction, endothelin 1
      (ET-1) plasma levels and subclinical inflammation in primary open angle glaucoma
      (POAG) patients. MAIN METHODS: We enrolled 40 POAG patients with progressive
      visual field damage, although well controlled intraocular pressure (IOP) and
      compared to age and sex matched healthxy subjects. Each patient underwent an
      ophthalmological examination, a standard achromatic perimetry (SAP), blood
      sampling to assess ET-1 plasma levels, an objective assessment of cellularity
      within the anterior chamber (FLARE) and measurement of flow mediated dilation
      (FMD) with high resolution 2-dimensional ultrasonographic imaging of the brachial
      artery. KEY FINDINGS: At baseline, POAG patients, compared to healthy controls,
      showed an increase of ET-1 plasma levels: 2.83 +/- 0.28 pg/ml vs. 1.75 +/- 0.25
      pg/ml (p<0.001), lower FMD values 4.46 +/- 1.28% vs. 13.18 +/- 2.80% (p<0.001)
      and increased FLARE values 9.98 +/- 0.97 photons/ms vs. 5.87 +/- 0.64 photons/ms
      (p<0.001). A follow up after 1 year revealed a further increase of ET-1 plasma
      levels (to 3.68 +/- 0.60; p<0.001) and decrease of FMD (3.52 +/- 1.28; p>0.001).
      SIGNIFICANCE: The increase of ET-1 in POAG patients is related to vascular
      dysfunction (r=0.942; p=0.001) and vascular dysfunction is related to sub
      clinical intraocular inflammation (r=0.968; p=0.001). Thus ET-1 and vascular
      dysfunction related to sub-clinical inflammation may play a key role in
      determining a progressive visual field damage in POAG patients who present a well
      controlled IOP.

PMID- 22406081
TI  - Anatomy and fine structure of pedicellar glands in phoretic deutonymphs of
      uropodid mites (Acari: Mesostigmata).
AB  - Phoretic deutonymphs of uropodid mites are attached to their carrier via an anal
      pedicel which is formed by a secretion from the pedicellar gland. Since the
      ultrastructure of the pedicel and pedicellar gland has never been investigated,
      we studied these structures in three species, Uropoda orbicularis (Muller),
      Uroobovella marginata (Koch), and Trichouropoda ovalis (Koch) by light (LM) and
      electron microscopy (TEM, SEM). In addition, the pedicel in Uroobovella nova
      (Oudemans) was documented in SEM. The pedicellar gland is a distinct globular
      structure comprised of three types of secretory cells (A-, B-, and C-types) with
      apical parts directed towards a junctional zone of postcolon and anal atrium.
      Secretory cells of the A-type are located dorsally, whereas B-type cells are
      central, and C-type cells are distributed ventrally or both ventrally and
      dorsally. Protrusions of visceral muscle cells are distributed on the external
      surface of the gland. The cuticle-lined anal atrium is large and located between
      the gland and dorso-anal muscles. The pedicel is composed of a main stalk and two
      extended extremities: one adhering to the anal region of the deutonymph and a
      second connected to the cuticle of the carrier. In each case, the anal atria were
      empty, whereas the pedicellar material was located outside of the mite body.

PMID- 22406082
TI  - Antennal lobe organization in the slender pigeon louse, Columbicola columbae
      (Phthiraptera: Ischnocera).
AB  - This study reports on the structure of the antennal lobe of the pigeon louse,
      Columbicola columbae. Anterograde staining of antennal receptor neurons revealed
      an antennal lobe with a few diffuse compartments, an organization distinct from
      the typical spheroidal glomerular structure found in the olfactory bulb of
      vertebrates and the antennal lobe of many other insects. This anatomical
      arrangement of neuronal input is somewhat reminiscent of the aglomerular antennal
      lobe previously reported in psyllids and aphids. As in psyllids, reports on the
      odor-mediated behavior of C. columbae suggest that the olfactory sense is
      important in these animals and indicates that a glomerular organization of the
      antennal lobe may not be necessary to subtend odor-mediated behaviors in all
      insects. The diffuse or aglomerular antennal lobe organization found in these two
      Paraneopteran insect orders might represent an independently evolved reduction
      due to similar ecological constraints.

PMID- 22406083
TI  - HIV-1 and HIV-2 infections induce autophagy in Jurkat and CD4+ T cells.
AB  - Autophagy plays important roles during innate and adaptive immune responses to
      pathogens, including virus infection. Viruses develop ways to subvert the pathway
      for their own benefit in order to escape restriction by autophagy, leading to
      increased viral replication and/or control over apoptosis of their host cells.
      The effects of HIV infection on the autophagic pathway in host cells have been
      little documented. Using the susceptible Jurkat cell line and CD4(+) T cells, we
      studied the relationship of HIV-1 and -2 infections with autophagy. We found that
      HIV infections significantly increase transcription of ULK1, a member of the
      autophagy-initiated complex. Two ubiquitin-like conjugation systems, the Atg12
      conjugation system and the microtubule-associated protein L chain 3 (LC3)
      conjugation system that control the elongation of the autophore to form the
      autophagosome, were activated after HIV infection, with upregulation of Atg12
      Atg5 complex and increased transcription of LC3, and formed more autophagosome in
      infected cells detected using an EM assay. We also found that HIV-1 induced more
      autophagic death in Jurkat cells relative to HIV-2, and the inhibition of
      autophagy with 3MA and Beclin-1 knockdown decreased HIV-1 replication
      significantly. The results indicate that HIV is able to induce the autophagic
      signaling pathway in HIV-infected host cells, which may be required for HIV
      infection-mediated apoptotic cell death.

PMID- 22406084
TI  - Caveolin-1 silencing arrests the proliferation of metastatic lung cancer cells
      through the inhibition of STAT3 signaling.
AB  - Cav-1 is an essential structural constituent of caveolae implicated in mitogenic
      signaling, oncogenesis, angiogenesis, neurodegenerative diseases and senescence.
      Its role as a tumor suppressor gene or as a tumor promoter seems to strictly
      depend on cell type and tumor stage/grade. The high expression of Cav-1 in some
      tumors in vivo, amongst which lung adenocarcinoma, is associated with increased
      tumor aggressiveness, metastatic potential and suppression of apoptosis. In the
      present study we investigated the role of Cav-1 in metastatic lung cancer
      proliferation. Cell lines were from metastatic lesions of lung adenocarcinoma
      (RAL) and of small cell lung carcinoma (SCLC-R1), in which we found Cav-1
      expressed at high levels. Results show that siRNA-mediated down-regulation of Cav
      1 caused stable arrest of proliferation in both cell lines. A marked reduction of
      cyclin D1 and of CDK4 expression was evident in the cells transfected with Cav-1
      siRNA and consequently of phospho-Rb on ser(795) and ser(780). Furthermore, a
      significant decrease of the expression of phosphorylated AKT and of its down
      stream effectors phosphorylated ERK and STAT3 was evident. Together, these
      findings indicate that Cav-1 silencing induces an arrest of human metastatic lung
      proliferation in vitro by a new inhibitory pathway in lung cancer and provide new
      insights into the molecular mechanisms underlying the pro-survival and tumor
      promoting functions of Cav-1.

PMID- 22406085
TI  - Alveolar preservation with high inflation pressure and intermediate oxygen
      concentration reduces ischemia-reperfusion injury of the lung.
AB  - BACKGROUND: This study investigated the optimal alveolar oxygen concentration and
      inflation pressure during ischemia that reduces lung ischemia-reperfusion injury
      (LIRI). METHODS: Male Sprague-Dawley rats (n = 66) underwent 150 minutes of left
      lung ischemia by hilar clamping at an airway inflation pressure (P) of 5 or 30 cm
      H(2)O and an oxygen (O) concentration of 0%, 30%, or 100% (P(5)O(0), P(5)O(30),
      P(5)O(100), P(30)O(0), P(30)O(30) and P(30)O(100) groups). Lungs preserved with
      0% oxygen were inflated with 100% nitrogen. Measurements of arterial blood gas
      values, pulmonary compliance, histology, flow cytometry of bronchoalveolar lavage
      fluid were performed on day 2 postoperatively. RESULTS: Inflation with 30 cm
      H(2)O resulted in increased partial pressure of arterial oxygen (Pao(2)) and lung
      compliance, decreased diffuse alveolar damage, and less infiltration of CD4(+)
      and CD8(+) lymphocytes and major histocompatibility complex class II-positive
      (MHCII(+)) antigen-presenting cells (APCs) in the left lung on day 2 compared
      with clamping at an airway inflation pressure of 5 cm H(2)O. The 100% oxygen
      groups demonstrated a lower Pao(2) and a decreased pulmonary compliance than 30%
      oxygen groups. More CD8(+) lymphocytes and MHCII(+) APCs were found in the
      P(5)O(100) group than in the P(5)O(0) and P(5)O(30) groups. CONCLUSION: Alveolar
      inflation with a pressure of 30 cm H(2)O and an oxygen concentration of 30%
      decreases the severity of LIRI. The protective effect is mainly due to
      hyperinflation and, to a lesser extent, through oxygen concentration.

PMID- 22406086
TI  - Treatment of BK viremia in a pediatric heart transplant recipient.

PMID- 22406087
TI  - Ring chromosome 20.
AB  - Ring Chromosome 20 syndrome is a rare chromosomal disorder characterized by
      refractory epilepsy, with seizures in wakefulness and sleep, behavioral problems
      and mild to severe cognitive impairment. Facial dysmorphism or other congenital
      malformations are rarely reported making it difficult to diagnose the syndrome
      based on clinical findings alone. Therefore, diagnosis requires cytogenetic
      testing. More than 100 cases have been published since the initial report in
      1972. In some patients, the ring (20) is found in all cells analyzed and in these
      cases, the ring is almost always accompanied by deletions of 20pter and/or
      20qter. However, in the majority of cases the ring is present in only a
      proportion of cells, with two normal 20's in the remaining cells (mosaicism), and
      in these cases, no deletions of chromosome 20 have been observed. Patients with
      supernumerary r(20) chromosomes have also been identified, but these individuals
      do not generally have seizures and are not discussed in this review.
      Characterization by fluorescence in situ hybridization and array-based analysis
      has shed insight into the molecular composition and possible mechanisms of ring
      formation, in both the mosaic and non-mosaic patients. The age of onset of
      seizures correlates with the percentage of cells with the ring in mosaic
      patients. While the underlying etiology of the phenotype is still not understood,
      evidence is accumulating which suggests the deletion of candidate genes on
      chromosome 20 is not responsible. Cytogenetic analysis, rather than chromosomal
      microarray analysis is recommended for diagnosis of this syndrome, as the mosaic
      cases do not have copy number alterations and are therefore not identified by
      array-based analysis.

PMID- 22406088
TI  - Co-occurrence of Marfan syndrome and schizophrenia: what can be learned?
AB  - We report on a young female patient diagnosed with Marfan syndrome upon admission
      to the psychiatric hospital for a first psychosis. Mutation analysis of FBN1
      identified a de novo nonsense mutation (p.Glu178X). This finding implies co
      occurrence of schizophrenia and Marfan syndrome, an observation that has been
      reported several times in the past. Although, this co-occurrence can be
      coincidental, several arguments provide strong evidence that Marfan syndrome and
      schizophrenia might share common etiological pathways. This observation can be
      important in light of both the etiology of schizophrenia and the diagnosis of
      Marfan syndrome.

PMID- 22406089
TI  - Unbalanced three-way chromosomal translocation leading to deletion 18q and
      duplication 20p.
AB  - In 1980, a case report on a boy with cleft palate, club feet, dysmorphic
      features, and developmental delay was published by Bijlsma as a possible distinct
      syndrome. This case is listed in the London Medical Databases version 1.0. We
      have reevaluated this patient at adult age. Using high resolution karyotyping and
      Affymetrix 250k SNP array analysis we identified an unbalanced three-way
      translocation with breakpoints at 17q22, 18q22.1, and 20p12.2 leading to deletion
      18q and duplication 20p. Also, a 715 kb duplication in 1p34.2 and a 245 kb
      deletion at 1p21.1 were found. Mental retardation, cleft palate, and club feet
      have repeatedly been reported in deletion 18q patients and therefore we conclude
      that most of the patient's features can be explained by an 18q deletion.

PMID- 22406090
TI  - Effect of cell membrane thiols and reduction-triggered disassembly on
      transfection activity of bioreducible polyplexes.
AB  - Bioreducible polyplexes are promising vectors for delivery of nucleic acids due
      to low toxicity and favorable transfection activity. The often improved
      transfection is usually explained by enhanced intracellular reductive disassembly
      of the polyplexes. This study evaluated the effect of enhanced reductive
      disassembly on transfection activity of plasmid DNA and antisense oligonucleotide
      (AON) polyplexes based on a series of bioreducible poly(amido amine)s (PAA). We
      found that the presence of disulfide bonds in PAA had no effect on nucleic acid
      binding, hydrodynamic size and zeta potential of polyplexes. Increasing the
      disulfide content in PAA increased susceptibility to reduction-triggered DNA and
      AON release from the polyplexes. Increasing the disulfide content in PAA
      increased DNA transfection but had no effect on AON transfection. Plasma membrane
      protein thiols played a key role in the observed enhancement of DNA transfection.
      The presence of disulfide bonds in PAA had no significant effect on the rate of
      intracellular DNA clearance, suggesting that enhanced intracellular disassembly
      of the bioreducible polyplexes is not a major contributing factor to the improved
      transfection activity.

PMID- 22406091
TI  - Conjugation of paclitaxel on adeno-associated virus (AAV) nanoparticles for co
      delivery of genes and drugs.
AB  - We have investigated the use of adeno-associated virus (AAV) nanoparticles as
      platforms for the co-delivery of genes and drugs to cancer cells. With its
      regular geometry, nanoscale dimensions, lack of pathogenicity, and high infection
      efficiency in a wide range of human cells and tissues, AAV is a promising vector
      for such applications. We tested the covalent conjugation of paclitaxel onto
      surface-exposed lysine residues present on the virus capsid. Immunoblotting
      results suggest successful attachment of drug molecules to the virus
      nanoparticles. Favorably, the reaction conditions did not reduce the gene
      delivery efficiency of the AAV vectors. Unfortunately, decrease in cancer cell
      viability was not observed with our AAV-taxol conjugates. For future attempts at
      conjugating drugs to the AAV nanoparticle, we have identified several
      improvements than can be considered to achieve the desired cytotoxicity in target
      cells.

PMID- 22406092
TI  - Synthesis of a novel CS-g-MMCs conjugate and the inhabitation on the
      proliferation of Tenon's capsule fibroblasts in vitro.
AB  - A novel anti-proliferative macromolecular conjugate, CS-g-MMCs, was synthesized
      in order to decrease the cytotoxicity of Mitomycin C (MMC) which was a
      traditional anti-proliferative agent of fibroblast in trabeculectomy. The
      structure of CS-g-MMCs was characterized by (1)H NMR, FT-IR spectroscopy and GPC
      analysis. The grafting degree (dg) of MMC onto chitosan (CS) was determined to be
      in the range of 2.8-11.3%, which could be controlled by variation of the molar
      ratios of MMC to oxidized chitosan (CS-CHO). In the drug release profiles of CS-g
      MMCs in vitro, an initial burst followed by slow leakage was observed, and
      addition of acid or lysozyme obviously accelerated the MMC release. The MTS assay
      indicated that CS-CHO of 8 mg/ml has no cytotoxicity against human Tenon's
      capsule fibroblasts (HTCFs). The inhibition of HTCFs proliferation by CS-g-MMCs
      increased along with increasing the dg of conjugate. The CS-g-MMCs also caused
      the apoptosis of HTCFs and interfered in the active DNA synthesis in HTCFs.
      Furthermore, the expression of a-SMA at gene and protein levels were obviously
      lower when HTCFs were treated with CS-g-MMCs, as compared to MMC or blend of
      MMC/CS-CHO (p<0.05). Our results primarily demonstrated that the CS-g-MMCs
      conjugates have low cytotoxicity and have the effect to inhibit fibroblast
      proliferation.

PMID- 22406093
TI  - Bilateral popliteal artery aneurysms in a young man with Loeys-Dietz syndrome.
AB  - Loeys-Dietz syndrome is a recently described genetic connective tissue disorder.
      The syndrome is associated with multiple nonvascular phenotypic anomalies but
      also aggressive arteriopathy, which has so far principally been shown to cause
      aortic root dilatation with subsequent dissection and rupture. We report the
      first ever case of a young man diagnosed with Loeys-Dietz syndrome with
      asymptomatic large bilateral popliteal artery aneurysms. We have successfully
      resected these aneurysms and revascularized with synthetic graft.

PMID- 22406094
TI  - Impact of antiepileptic drugs on genesis of psychosis.
AB  - Opinions regarding the impact of antiepileptic drugs (AEDs) on the genesis of
      psychotic symptoms are varied. To re-examine this issue, the records of adult
      patients with partial epilepsy and newly added AEDs were retrospectively
      surveyed. The types of newly added AEDs and clinical characteristics were
      compared between 38 patients with active psychosis and 212 without psychotic
      history during a follow-up period of 3 to 6 months after initiation of AED
      administration. Using multivariate logistic regression analysis, the significance
      of possible predictive variables for development of psychosis was evaluated,
      which demonstrated that use of zonisamide (ZNS) and phenytoin (PHT), presence of
      complex partial seizures (CPS), and low intelligence level were significantly
      correlated with psychosis. We concluded that ZNS and PHT are possible risk
      factors for development of psychosis along with clinical variables, including the
      presence of CPS and low intelligence level.

PMID- 22406095
TI  - Is it possible to extract a fingerprint for early breast cancer via EEG analysis?
AB  - People with abnormal breast tissue can eventually present breast cancer symptoms.
      The aim of this paper is to examine new prognostic methods for breast cancer
      using electroencephalographic techniques (EEG). Since it is known that electrical
      brain activity can be recorded by EEG, and since proteins and genes affect the
      electrical activity of the brain via the control of the flow of Na(+) and K(+)
      ions, and also given the fact that breast cancer and many other types of cancer
      are associated with 14-3-3 protein and genes, we hypothesize that there is a
      relationship between breast cancer and EEG. We examine the theoretical linkages
      between EEG, genes and proteins, and breast cancer, and propose the development
      of an intelligent technique for associating EEG with the early stages of breast
      cancer (i.e., atypical hyperplasia) as a fingerprint characteristic. This novel
      approach may provide the means for a new diagnostic and prognostic approach to
      early stage breast cancer, and other cancers.

PMID- 22406096
TI  - The possible underlying pathophysiological mechanisms for development of multiple
      sclerosis in familial Mediterranean fever.
AB  - Patients with familial Mediterranean fever (FMF) have a susceptibility to the
      development of multiple sclerosis (MS). Here, we will propose the possible
      underlying pathophysiological mechanisms of this predisposition. Inflammation,
      disruption of blood-brain barrier (BBB), mitochondrial energy deficit,
      demyelination, and axonal damage, which play an important role in the
      pathogenesis of MS, may occur during the course of FMF. Most FMF patients have
      homozygous mutations in the MEFV gene that codes for the protein pyrin. Also,
      pyrin mutations were found about 3.5 times higher in the MS patients than the
      healthy control group. Pyrin is implicated in the maturation and secretion of the
      proinflammatory cytokine IL-1beta. IL-1beta is a major mediator of fever and
      systemic inflammation, and mononuclear cells from FMF patients release higher
      levels of IL-1beta. Moreover, IL-1 plays a significant role in the regulation of
      the T-cells, and it is considered an essential cytokine for the Th cell
      differentiation that implicated in the MS pathogenesis. In addition, endothelial
      dysfunction and vasculitis in FMF may cause BBB breakdown that is the first step
      in the development of MS lesions. Apart from this, damage can occur in myelin and
      mitochondria proteins due to high body temperature that arises during the FMF
      attacks. Whereas the protein damage in myelin results in demyelination, and the
      protein damage in mitochondria causes lack of energy. Both situations play a part
      in the pathogenesis of MS. Due to mitochondrial energy deficit, remyelination may
      not be achieved, and therefore, axonal damage increases. Thus, at the end of
      these pathophysiological processes, MS findings may occur in the FMF patients
      especially with irregular use of colchicine.

PMID- 22406097
TI  - Dose-dependent sustained local release of dexamethasone from biodegradable
      thermosensitive hydrogel of PEG-PLGA-PEG triblock copolymers in the possible
      prevention of TMJ re-ankylosis (Arakeri's TMJ release technique).
AB  - Temporomandibular joint (TMJ) ankylosis is a devastating anatomico-pathological
      condition which severely affects the quality of human health. Over the last 70
      years various treatments have been described to treat this distressing condition.
      But no single method has uniformly produced successful results. Although various
      surgical techniques have been improved periodically, the treatment results remain
      inefficient due to its recurrence as TMJ re-adhesion. Since recurrence remains as
      a problem in many cases, the TMJ ankylosis presents a major therapeutic challenge
      in head and neck surgery. The re-ankylosis is a unique phenomenon that so far has
      defied a full and logical explanation, based upon biological and mechanical
      factors that are linked together in a coherent fashion. Many factors have been
      implicated in the development of re-adhesion following TMJ surgery. But still the
      mechanism by which the TMJ re-adhesion develops is unclear. Hence, TMJ ankylosis
      demands an alternative effective treatment modality to prevent its recurrence as
      re-ankylosis. This paper postulates some critical biological factors responsible
      for re-ankylosis based on which a novel treatment modality is also proposed.

PMID- 22406098
TI  - Integrated bioprocess for long-term continuous cultivation of Clostridium
      acetobutylicum coupled to pervaporation with PDMS composite membranes.
AB  - A continuous cultivation of Clostridium acetobutylicum ATCC 824 is described
      using a two-stage design to mimic the two phases of batch culture growth of the
      organism. A hydrophobic pervaporation unit was coupled to the second fermentor
      containing the highest solvent titers. This in situ product recovery technology
      efficiently decreased butanol toxicity in the fermentor while the permeate was
      enriched to 57-195 g L(-1) total solvents depending on the solvent concentrations
      in the fermentor. By the alleviation of product inhibition, the glucose
      concentration could be increased from 60 to 126 g L(-1) while the productivity
      increased concomitantly from 0.13 to 0.30 g L(-1)h(-1). The continuous
      fermentation was conducted for 1172 h during which the pervaporation was coupled
      to the second fermentor for 475 h with an average flux of 367 g m(-2)h(-1). The
      energy consumption was calculated for a 2 wt.% n-butanol fermentation broth and
      compared with the conventional process.

PMID- 22406099
TI  - Biomethane potential of the POME generated in the palm oil industry in Ghana from
      2002 to 2009.
AB  - The palm oil industry experienced significant improvement in its production level
      from 2002 to 2009 from the established companies, medium scale mills (MSM), small
      scale and other private holdings (SS and OPH) groups. However, the same cannot be
      said for treatment of the palm oil mill effluent (POME) produced. The quantity of
      crude palm oil (CPO) produced in Ghana from 2002 to 2009 and IPCC guidelines for
      National Greenhouse Gas Inventories, specifically on industrial wastewater were
      used in this study. During this period about 10 million cubic metres of POME was
      produced translating into biomethane potential of 38.5 million m(3) with
      equivalent of 388.29 GW h of energy. A linear growth model developed to predict
      the equivalent carbon dioxide (CO(2)) emissions indicates that if the biomethane
      is not harnessed then by 2015 the untreated POME could produce 0.58 million
      tCO(2)-eq and is expected to increase to 0.70 million tCO(2)-eq by 2020.

PMID- 22406100
TI  - Influence of ligninolytic enzymes on straw saccharification during fungal
      pretreatment.
AB  - Solid state and submerged fermentations in the presence of white-rot
      basidiomycetes (Bjerkandera adusta, Fomes fomentarius, Ganoderma resinaceum,
      Irpex lacteus, Phanerochaete chrysosporium, Trametes versicolor and basidiomycete
      Euc-1) and the litter-decomposing basidiomycete Lepista nuda were evaluated as a
      pretreatment to increase enzymatic saccharification of wheat straw. Enzymatic
      hydrolysis of holocellulose after solid state pretreatment showed a significant
      (P<0.05) increase of saccharification process for T. versicolor, Euc-1, G.
      resinaceum and I. lacteus, being T. versicolor (strain Tv2) the best one with a
      sugar yield increase of 91% compared with untreated straw. In submerged medium
      the pretreatment with I. lacteus, Euc-1 and P. chrysosporium enhanced
      saccharification but at a lesser extent. Covariance analysis was used to evaluate
      the relationships between ligninolytic enzymes (lignin peroxidase, manganese
      dependent peroxidase and laccase) and saccharification increase. Results showed
      that only the presence of lignin peroxidase during pretreatment can lead to a
      significant (P<0.05) increase in the saccharification yield.

PMID- 22406101
TI  - Preventing cognitive decline in older African Americans with mild cognitive
      impairment: design and methods of a randomized clinical trial.
AB  - Mild Cognitive Impairment (MCI) affects 25% of older African Americans and
      predicts progression to Alzheimer's disease. An extensive epidemiologic
      literature suggests that cognitive, physical, and/or social activities may
      prevent cognitive decline. We describe the methods of a randomized clinical trial
      to test the efficacy of Behavior Activation to prevent cognitive decline in older
      African Americans with the amnestic multiple domain subtype of MCI. Community
      Health Workers deliver 6 initial in-home treatment sessions over 2-3 months and
      then 6 subsequent in-home booster sessions using language, materials, and
      concepts that are culturally relevant to older African Americans during this 24
      month clinical trial. We are randomizing 200 subjects who are recruited from
      churches, senior centers, and medical clinics to Behavior Activation or
      Supportive Therapy, which controls for attention. The primary outcome is episodic
      memory as measured by the Hopkins Verbal Learning Test-Revised at baseline and at
      months 3, 12, 18, and 24. The secondary outcomes are general and domain-specific
      neuropsychological function, activities of daily living, depression, and quality
      of-life. The negative results of recent clinical trials of drug treatments for
      MCI and Alzheimer's disease suggest that behavioral interventions may provide an
      alternative treatment approach to preserve cognition in an aging society.

PMID- 22406102
TI  - Acupuncture for dysphagia after chemoradiation in head and neck cancer: rationale
      and design of a randomized, sham-controlled trial.
AB  - INTRODUCTION: Dysphagia is a common side effect following chemoradiation therapy
      (CRT) in head and neck cancer (HNC) patients. Current dysphagia management
      includes swallowing therapy and dilation procedures, but these treatments have
      limitations. While acupuncture has been reported to positively impact swallowing
      function and quality of life (QOL) in patients with dysphagia, current evidence
      is inconclusive. MATERIAL AND METHODS: In an ongoing trial, 42 squamous cell
      carcinoma HNC patients, who are receiving platinum-based CRT with curative
      intent, are being recruited from a comprehensive cancer center. They are
      randomized to 12 sessions of either active acupuncture or to sham acupuncture
      during and following CRT over a 24-week period. Blinded research staff assesses
      outcomes at baseline, 20 weeks post-CRT (end of acupuncture), and 12 months after
      baseline (6-month follow-up). The primary outcome is change in M.D. Anderson
      Dysphagia Inventory score from baseline to 12 months. Secondary outcomes include
      QOL measures pertaining to HNC patients. In addition, a subset of study patients
      are tested for salivary flow rates and cytokines, including plasma transforming
      growth factor-beta1 and interleukin 6 (n=10 per arm), to preliminarily explore
      the biological mechanisms of acupuncture for dysphagia. DISCUSSION: This paper
      addresses unique challenges related to study design in nonpharmacological, sham
      controlled acupuncture trials including development of evidence-based credible
      verum and sham treatment protocols, blinding, and assuring fidelity of treatment.
      Results of this study will inform the feasibility of conducting a large scale
      trial and will provide preliminary evidence regarding the value of acupuncture
      for dysphagia in HNC patients.

PMID- 22406103
TI  - Determination of a highly selective mixed-affinity sigma receptor ligand, in rat
      plasma by ultra performance liquid chromatography mass spectrometry and its
      application to a pharmacokinetic study.
AB  - A selective, rapid and sensitive ultra performance liquid chromatography mass
      spectrometry (UPLC/MS) method was developed and validated to quantitate a highly
      selective mixed-affinity sigma receptor ligand, CM156 (3-(4-(4
      cyclohexylpiperazin-1-yl)butyl)benzo[d] thiazole-2(3H)-thione), in rat plasma.
      CM156 and the internal standard (aripiprazole) were extracted from plasma samples
      by a single step liquid-liquid extraction using chloroform. The analysis was
      carried out on an ACQUITY UPLCTM BEH HILIC column (1.7 MUm, 2.1 mm*50 mm) with
      isocratic elution at flow rate of 0.2 mL/min using 10mM ammonium formate in 0.1%
      formic acid and acetonitrile (10:90) as the mobile phase. The detection of the
      analyte was performed on a mass spectrometer operated in selected ion recording
      (SIR) mode with positive electrospray ionization (ESI). The validated analytical
      method resulted in a run time of 4 min and the retention times observed were
      2.6+/-0.1 and 2.1+/-0.1 min for CM156 and the IS, respectively. The calibration
      curve exhibited excellent linearity over a concentration range of 5-4000 ng/mL
      with the lower limit of quantification of 5 ng/mL. The intra- and inter-day
      precision values were below 15% and accuracy ranged from -6.5% to 5.0%. The mean
      recovery of CM156 from plasma was 96.8%. The validated method was applied to a
      pilot intravenous pharmacokinetic study in rats.

PMID- 22406104
TI  - Measurements of polybrominated diphenyl ethers and polychlorinated biphenyls in a
      single drop of blood.
AB  - A quantitative method that requires only a small volume (50MUL) of blood has been
      developed for the determination of polybrominated diphenyl ethers (PBDEs) and
      polychlorinated biphenyls (PCBs). Target analytes in both plasma sample (DBSV)
      and dried blood spot (DBS) were analyzed by a gas chromatography/high resolution
      mass spectrometer (GC/HRMS). Measurements of standard reference materials by the
      developed method were in agreement with those certified values. Linear
      correlation coefficients were found to be 0.9984 and 0.9965 for DBS and DBSV
      analysis, respectively. Other analytical criteria, such as limits of detection,
      recoveries, precision, accuracy and linearity of the proposed method are also
      reported. From recovery studies, the addition of formic acid to the extraction
      solvent was found to be effective in extracting PBDEs and PCBs from filter paper.
      The PBDE and PCB levels in spiked DBS were monitored at room temperature for up
      to 30 days and the variations of target analytes were found to be insignificant.
      Our results suggest that DBS sampling technique is feasible for PBDE and PCBs
      biomonitoring in human population.

PMID- 22406105
TI  - In vitro enantioselective metabolism of TJ0711 hydrochloride by human liver
      microsomes using a novel chiral liquid chromatography-tandem mass spectrometry
      method.
AB  - A novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method
      employing chiral analytical techniques was developed and validated for in vitro
      enantioselective metabolic stability study of racemic 1-[4-(2-methoxyethyl)
      phenoxy]-3-[[2-(2-methoxyphenoxy) ethyl]amino]-2-propanol hydrochloride (TJ0711
      HCl), a newly developed vasodilatory beta-blocker. Robust enantiomeric
      separations were achieved on a chiral SUMICHIRAL OA-2500 column using ethanol and
      hexane (40:60, v/v) as a mobile phase. Metabolic stability results demonstrated
      that both TJ0711 enantiomers underwent a rapid phase I metabolism, but
      preferential metabolism of R-TJ0711 was observed. Our previously reported ultra
      performance liquid chromatography-multiple reaction monitoring-information
      dependent acquisition-enhanced product ion (UPLC-MRM-IDA-EPI) method was finally
      chosen for metabolite profiling study of TJ0711 enantiomers, because the newly
      developed HPLC-based method resulted in compromised chromatographic separation,
      particularly for TJ0711 metabolites. A number of metabolic products were detected
      and the structures of formed metabolites were predicted. Similar to racemic
      TJ0711 HCl, demethylation and hydroxylation were proposed to be the principle
      metabolism pathways during in vitro incubations of each enantiomer with human
      liver microsomes.

PMID- 22406106
TI  - 3-(4-(tert-Octyl)phenoxy)propane-1,2-diol suppresses inflammatory responses via
      inhibition of multiple kinases.
AB  - Novel anti-inflammatory compounds were synthesised by derivatization of
      militarin, a compound isolated from Cordyceps militaris that is an
      ethnopharmacologically well-known herbal medicine with multiple benefits such as
      anti-cancer, anti-inflammatory, anti-obesity, and anti-diabetic properties. In
      this study, we explored the in vitro and in vivo anti-inflammatory potencies of
      these compounds during inflammatory responses, their inhibitory mechanisms, and
      acute toxicity profiles. To do this, we studied inflammatory conditions using in
      vitro lipopolysaccharide-treated macrophages and several in vivo inflammatory
      models such as dextran sodium sulphate (DSS)-induced colitis, EtOH/HCl-induced
      gastritis, and arachidonic acid-induced ear oedema. Methods used included real
      time PCR, immunoblotting analysis, immunoprecipitation, reporter gene assays, and
      direct kinase assays. Of the tested compounds, compound III showed the highest
      nitric oxide (NO) inhibitory activity. This compound also inhibited the
      production of prostaglandin (PG)E(2) at the transcriptional level by suppression
      of Syk/NF-kappaB, IKKE/IRF-3, and p38/AP-1 pathways in lipopolysaccharide (LPS)
      activated RAW264.7 cells and peritoneal macrophages. Consistent with these
      findings, compound III strongly ameliorated inflammatory symptoms in colitis,
      gastritis, and ear oedema models. In acute toxicity tests, there were no
      significant differences in body and organ weights, serum parameters, and stomach
      lesions between the untreated and compound III-treated mice. Therefore, this
      compound has the potential to be served as a lead chemical for developing a
      promising anti-inflammatory drug candidate with multiple kinase targets.

PMID- 22406107
TI  - The inhibitory glutathione transferase M2-2 binding site is located in divergent
      region 3 of the cardiac ryanodine receptor.
AB  - The muscle-specific glutathione transferase GSTM2-2 modulates the activity of
      ryanodine receptor (RyR) calcium release channels: it inhibits the activity of
      cardiac RyR (RyR2) channels with high affinity and activates skeletal RyR (RyR1)
      channels with low affinity. The C terminal domain of GSTM2-2 (GSTM2C) alone
      physically binds to RyR2 and inhibits its activity, but it does not bind to RyR1.
      We have now used yeast two-hybrid analysis, chemical cross-linking, intrinsic
      tryptophan fluorescence and Ca(2+) release studies to determine that the binding
      site for GSTM2C is in divergent region 3 (D3) of RyR2. The D3 region encompasses
      residues 1855-1890 in RyR2. Specific mutagenesis shows the binding primarily
      involves electrostatic interactions with residues K1875, K1886, R1887 and K1889,
      all residues that are present in RyR2, but not in RyR1. The significant sequence
      differences between the D3 regions of RyR2 and RyR1 explain why GSTM2-2
      specifically inhibits RyR2. This specific inhibition of RyR2 could modulate Ca
      cycling and be useful for the treatment of heart failure. RyR2 inhibition during
      diastole may improve filling of the SR with Ca(2+) and improve contractility.

PMID- 22406108
TI  - Towards licensing of CP7_E2alf as marker vaccine against classical swine fever
      Duration of immunity.
AB  - Classical swine fever (CSF) marker vaccine candidate CP7_E2alf was tested in a
      "duration of immunity" trial according to the World Organisation for Animal Heath
      (OIE) guidelines. To this means, 15 weaner pigs were either orally or
      intramuscularly vaccinated with a single dose of CP7_E2alf vaccine produced under
      Good Laboratory Practice (GLP) conditions. Ten additional pigs were included as
      controls. Six months later, all animals were oronasally challenged with highly
      virulent CSF virus (CSFV) strain "Koslov". Upon vaccination, all but one orally
      and all intramuscularly vaccinated pigs developed rising and later on stable CSFV
      glycoprotein E2-specific antibodies. In contrast, no CSFV E(rns)-specific
      "marker" antibodies were detectable prior to challenge infection. None of the co
      housed control animals seroconverted. Upon challenge infection, all seropositive
      animals were protected from lethal challenge, whereas all control animals and the
      non-responder developed severe signs of CSF. One control animal recovered, the
      others had to be euthanised due to animal welfare reasons between days 4 and 7
      post challenge infection. All protected animals showed quickly rising
      neutralizing antibodies reaching high titres by the end of the trial. At the end
      of the trial, the marker ELISA was positive for most challenged animals that
      survived the CSFV infection (27 out of 30). Using reverse transcription
      polymerase chain reaction, low level genome detection was seen in all vaccinated
      animals between days 4 and 10 post challenge infection, but no virus could be
      isolated from any samples of these animals. The OIE guidelines require
      seroconversion in at least 8 out of 10 vaccinated animals. This requirement was
      fulfilled. Moreover, only control animals should die. With this requirement, only
      the intramuscular vaccination fully complied as one orally vaccinated pig did not
      respond. Concluding, CP7_E2alf induced stable antibodies that led to protection
      from lethal challenge with highly virulent CSFV strain "Koslov" six months after
      vaccination, with the exception of one non-responder after oral vaccination.

PMID- 22406109
TI  - The recombinant globular head domain of the measles virus hemagglutinin protein
      as a subunit vaccine against measles.
AB  - Despite the availability of live attenuated measles virus (MV) vaccines, a large
      number of measles-associated deaths occur among infants in developing countries.
      The development of a measles subunit vaccine may circumvent the limitations
      associated with the current live attenuated vaccines and eventually contribute to
      global measles eradication. Therefore, the goal of this study was to test the
      feasibility of producing the recombinant globular head domain of the MV
      hemagglutinin (H) protein by stably transfected human cells and to examine the
      ability of this recombinant protein to elicit MV-specific immune responses. The
      recombinant protein was purified from the culture supernatant of stably
      transfected HEK293T cells secreting a tagged version of the protein. Two
      subcutaneous immunizations with the purified recombinant protein alone resulted
      in the production of MV-specific serum IgG and neutralizing antibodies in mice.
      Formulation of the protein with adjuvants (polyphosphazene or alum) further
      enhanced the humoral immune response and in addition resulted in the induction of
      cell-mediated immunity as measured by the production of MV H-specific interferon
      gamma (IFN-gamma) and interleukin 5 (IL-5) by in vitro re-stimulated splenocytes.
      Furthermore, the inclusion of polyphosphazene into the vaccine formulation
      induced a mixed Th1/Th2-type immune response. In addition, the purified
      recombinant protein retained its immunogenicity even after storage at 37 degrees
      C for 2 weeks.

PMID- 22406110
TI  - Dynamic analysis of interhospital collaboration and competition: empirical
      evidence from an Italian regional health system.
AB  - BACKGROUND: Policymakers stimulate competition in universalistic health-care
      systems while encouraging the formation of service provision networks among
      hospital organizations. This article addresses a gap in the extant literature by
      empirically analyzing simultaneous collaboration and competition between
      hospitals within the Italian National Health Service, where important
      procompetition reforms have been implemented. PURPOSE: To explore how rising
      competition between hospitals relates to their propensity to collaborate with
      other local providers. METHODS: Longitudinal data on interhospital collaboration
      and competition collected in an Italian region from 2003 to 2007 are analyzed.
      Social network analysis techniques are applied to study the structure and
      dynamics of interhospital collaboration. Negative binomial regressions are
      employed to explore how interhospital competition relates to the collaborative
      network over time. RESULTS: Competition among providers does not hinder
      interhospital collaboration. Collaboration is primarily local, with resource
      complementarity and differentials in the volume of activity and hospital
      performance explaining the propensity to collaborate. CONCLUSIONS: Formation of
      collaborative networks among hospitals is not hampered by reforms aimed at
      fostering market forces. Because procompetition reforms elicit peculiar forms of
      managed competition in universalistic health systems, studies are needed to
      clarify whether the positive association between interhospital competition and
      collaboration can be generalized to other health-care settings.

PMID- 22406111
TI  - In the fast lane: large-scale bacterial genome engineering.
AB  - The last few years have witnessed rapid progress in bacterial genome engineering.
      The long-established, standard ways of DNA synthesis, modification, transfer into
      living cells, and incorporation into genomes have given way to more effective,
      large-scale, robust genome modification protocols. Expansion of these engineering
      capabilities is due to several factors. Key advances include: (i) progress in
      oligonucleotide synthesis and in vitro and in vivo assembly methods, (ii)
      optimization of recombineering techniques, (iii) introduction of parallel, large
      scale, combinatorial, and automated genome modification procedures, and (iv)
      rapid identification of the modifications by barcode-based analysis and
      sequencing. Combination of the brute force of these techniques with sophisticated
      bioinformatic design and modeling opens up new avenues for the analysis of gene
      functions and cellular network interactions, but also in engineering more
      effective producer strains. This review presents a summary of recent
      technological advances in bacterial genome engineering.

PMID- 22406112
TI  - Matrix metalloproteinases 1, 2, 3 and 9 functional single-nucleotide
      polymorphisms in idiopathic recurrent spontaneous abortion.
AB  - Idiopathic recurrent spontaneous abortion (IRSA) has been associated with
      abnormalities in the remodelling of endometrial extracellular matrix, as well as
      aberrant matrix metalloproteinase (MMP) gene expression in endometrium of IRSA
      women and chorionic villi of IRSA concept. This study investigated the
      association of five functional MMP gene promoter polymorphisms (MMP1 -1607 1G/2G,
      MMP2 -735 C/T, MMP2 -1306 C/T, MMP3 -1612 5A/6A and MMP9 -1562 C/T) with IRSA. A
      total of 149 couples with at least three consecutive IRSA and 149 fertile couples
      were included in a case-control study. Genotype analysis was performed using PCR
      restriction fragment length polymorphism. Statistically significant differences
      were found in distributions of MMP2 -735 CT (chi-squared 10.21, P=0.006; OR 2.15,
      95% CI 1.34-3.45, P=0.001), and MMP9 -1562 CC (chi-squared 9.06, P=0.010; OR
      2.21, 95% CI 1.30-3.80, P=0.004) between IRSA women and controls. Combined
      analysis of MMP gene polymorphisms did not increase their predictive value. There
      were no statistically significant differences in genotype and allele frequencies
      of any polymorphism between IRSA men and controls. MMP2 -735 C/T and MMP9 -1562
      C/T functional gene polymorphisms might be associated with an increased risk of
      IRSA in women. Considering the insufficient knowledge on genetic contribution to
      pregnancy loss, studies on genetic causes of idiopathic recurrent spontaneous
      abortion (IRSA) are of great importance. Development of a histologically and
      functionally normal endometrium is critical for subsequent endometrial
      decidualization, receptivity and implantation. The proper communication and
      interaction between maternal decidual cells and the embryo is essential for the
      establishment of a functional fetal-maternal interface. IRSA has been associated
      with abnormalities in the remodelling of endometrial extracellular matrix, as
      well as aberrant matrix metalloproteinase (MMP) gene expression in endometrium of
      IRSA women and chorionic villi of IRSA concepti. The aim of this study was to
      investigate the association of five functional MMP gene promoter polymorphisms
      with IRSA. A total of 149 couples with at least three consecutive IRSA and 149
      fertile couples were included in a case-control study. Genotype analysis was
      performed using polymerase chain reaction and restriction fragment length
      polymorphism. Statistically significant differences were found in distribution of
      MMP2 -735 CT and MMP9 -1562 CC genotypes between IRSA and control women. Combined
      analysis of MMP gene polymorphisms did not increase their predictive value. There
      were no statistically significant differences in distribution of genotype and
      allele frequencies of any polymorphism between IRSA men and controls. Our results
      demonstrate that MMP2 -735 C/T and MMP9 -1562 C/T functional gene polymorphisms
      might be associated with an increased risk of IRSA in women.

PMID- 22406113
TI  - Effect of adenomyosis on implantation.

PMID- 22406115
TI  - Discovery of a new binding mode for a series of liver X receptor agonists.
AB  - Structural modification of a series of dual LXRalpha/beta agonists led to the
      identification of a new class of LXRbeta partial agonists. An X-ray co-crystal
      structure shows that a representative member of this series, pyrrole 5, binds to
      LXRbeta with a reversed orientation compared to 1.

PMID- 22406114
TI  - Pregnancy and pregnancy-associated hormones alter immune responses and disease
      pathogenesis.
AB  - During pregnancy, it is evolutionarily advantageous for inflammatory immune
      responses that might lead to fetal rejection to be reduced and anti-inflammatory
      responses that promote transfer of maternal antibodies to the fetus to be
      increased. Hormones modulate the immunological shift that occurs during
      pregnancy. Estrogens, including estradiol and estriol, progesterone, and
      glucocorticoids increase over the course of pregnancy and affect transcriptional
      signaling of inflammatory immune responses at the maternal-fetal interface and
      systemically. During pregnancy, the reduced activity of natural killer cells,
      inflammatory macrophages, and helper T cell type 1 (Th1) cells and production of
      inflammatory cytokines, combined with the higher activity of regulatory T cells
      and production of anti-inflammatory cytokines, affects disease pathogenesis. The
      severity of diseases caused by inflammatory responses (e.g., multiple sclerosis)
      is reduced and the severity of diseases that are mitigated by inflammatory
      responses (e.g., influenza and malaria) is increased during pregnancy. For some
      infectious diseases, elevated inflammatory responses that are necessary to
      control and clear a pathogen have a negative consequence on the outcome of
      pregnancy. The bidirectional interactions between hormones and the immune system
      contribute to both the outcome of pregnancy and female susceptibility to disease.

PMID- 22406116
TI  - Discovery of loperamide as an antagonist of angiopoietin1 and angiopoietin2 by
      virtual screening.
AB  - The angiopoietin-Tie2 binding and related signal transduction pathways are
      crucial for vascular angiogenesis, blood vessel integrity and maturation. In this
      study, we preformed a virtual screening of small molecules targeting to Tie2. The
      binding site was selected at the extracellular ligand binding region of Tie2,
      rather than its conventional endocellular ATP binding region. It was found that
      loperamide, a widely-used antidiarrhea drug, was among the top hits. The binding
      between loperamide and Tie2 was confirmed by surface plasmon resonance (SPR)
      assay. Loperamide competitively inhibited the binding of both angiopoietin1 and
      angiopoietin2. These results indicate that loperamide is an antagonist of
      angiopoietin1 and angiopoietin2.

PMID- 22406117
TI  - Optimization of 2,4-diarylanilines as non-nucleoside HIV-1 reverse transcriptase
      inhibitors.
AB  - The current optimization of 2,4-diarylaniline analogs (DAANs) on the central
      phenyl ring provided a series of new active DAAN derivatives 9a-9e, indicating an
      accessible modification approach that could improve anti-HIV potency against wild
      type and resistant strains, aqueous solubility, and metabolic stability. A new
      compound 9e not only exhibited extremely high potency against wild-type virus
      (EC(50) 0.53 nM) and several resistant viral strains (EC(50) 0.36-3.9 nM), but
      also showed desirable aqueous solubility and metabolic stability, which were
      comparable or better than those of the anti-HIV-1 drug TMC278 (2). Thus, new
      compound 9e might be a potential drug candidate for further development of novel
      next-generation NNRTIs.

PMID- 22406118
TI  - Short cyclic peptides derived from the C-terminal sequence of alpha1-antitrypsin
      exhibit significant anti-HIV-1 activity.
AB  - Serpin A1 (alpha1-AT), the largest subgroup of serpins, presents in human plasma
      at high concentration and plays important regulatory roles in physiological and
      pathological processes. Accumulated evidence suggests that alpha1-AT may play a
      role in controlling HIV-1 infection. In this study, we designed and synthesized a
      set of short linear peptides derived from the C-terminal sequence of alpha1-AT.
      Since none of them showed significant anti-HIV-1 activity, we proceeded to
      synthesize four short cyclic peptides having 7 amino acids, and we found that
      three of them exhibited significant anti-HIV-1 activity. One of these cyclic
      peptides, designated CPM, inhibited HIV-1 entry and infection at low MUM level,
      indicating that these short cyclic peptides could serve as leads for the
      development of novel anti-HIV-1 therapeutics.

PMID- 22406121
TI  - Sevelamer hydrochloride binds phosphate released from phytate in chicks fed
      1alpha-hydroxy cholecalciferol.
AB  - OBJECTIVE: Hyperphosphatemia in animal models of human renal disease has been
      linked to increased risk of death. Phosphate binders (e.g., sevelamer
      hydrochloride) and plant-based, low phosphate diets are used to reduce dietary
      phosphate load; however, animal models show that treatment with active forms of
      vitamin D(3) (e.g., calcitriol, a renal disease therapy) renders plant phytate
      phosphate available for absorption. Using an established chick model, the
      effectiveness of sevelamer in preventing the apparent absorption of liberated
      phytate phosphate during active vitamin D use was investigated in two separate
      experiments. DESIGN: One-day-old chicks were fed ad libitum a basal diet
      containing deficient levels of inorganic phosphate (0.13%), but adequate in total
      phosphate (0.40%, 0.23% as phytate phosphate), with or without the inclusion of
      sevelamer hydrochloride (a phosphate binder), available inorganic phosphate, or
      active vitamin D as 1alpha-(OH) D(3). MAIN OUTCOME MEASURES: Plasma phosphate
      (mg/dL), total bone ash (%), and weight gain (g). RESULTS: Adding inorganic
      phosphate (0.36%) or 1alpha-(OH) D(3) increased plasma phosphate 49% and 48%,
      respectively (P < .0001), and bone ash 23% and 19%, respectively (P < .001). The
      addition of 1% sevelamer to the basal diet with added inorganic phosphate or
      1alpha-(OH) D(3) significantly decreased plasma phosphate by 28% and 20%,
      respectively (P < .01). CONCLUSION: Active vitamin D increased the availability
      of phytate phosphate for intestinal absorption in an animal model; however,
      sevelamer effectively reduced the availability of phosphate liberated from
      phytate. These data imply that sevelamer has phytate phosphate binding efficacy.

PMID- 22406120
TI  - Novel differential measurement of natural and added phosphorus in cooked ham with
      or without preservatives.
AB  - OBJECTIVE: Assessment of the quantity and chemical type of phosphorus (P) content
      in cooked ham products with or without preservatives using a novel biochemical
      procedure. METHODS: We examined the quantity and types of P in 40 samples of
      cooked ham, including 20 without and 20 with P-containing preservatives, which
      were purchased randomly from a grocery store in Italy. Food samples were analyzed
      for dry matter, nitrogen, fat, and P content. Novel spectrophotometric methods
      were used to measure total P and 3 different P subtypes, that is, water-soluble
      (inorganic) P including added preservatives and natural P derived from
      phospholipids and phosphoproteins, separately. RESULTS: Compared with hams
      without preservatives, hams with P-containing preservatives had significantly
      lower dry matter and protein and fat contents. There was 66% more inorganic P
      (IP) in ham with preservatives than in samples without preservatives (169 +/- 36
      vs. 102 +/- 16 mg/100 g, P < .001, respectively). There were no significant
      differences in P contents derived from proteins or lipids. The P-to-protein ratio
      was higher in ham samples with preservatives than in those without preservatives
      (16.1 +/- 4.0 and 9.8 +/- 0.8 mg/g, P < .001). The sum of measured IP and P from
      phospholipids and phosphoproteins was 91% +/- 4% of measured total P (207.1 +/-
      50.7 vs. 227.2 +/- 54.4 mg/100 g), indicating a small portion of unspecified P
      and/or under measurement. CONCLUSIONS: Novel differential dietary P measurement
      detects added P-containing preservatives. Cooked ham with preservatives has 66%
      more measurable IP and 64% higher P-to-protein ratio than ham without
      preservatives. The contribution of food added with P-containing preservatives to
      global dietary P burden can negatively influence chronic kidney disease outcome
      and counteract the efficacy of P-binder medications: this is an important topic
      that warrants additional investigations.

PMID- 22406119
TI  - Associations of dietary phosphorus intake, urinary phosphate excretion, and
      fibroblast growth factor 23 with vascular stiffness in chronic kidney disease.
AB  - OBJECTIVE: Elevated serum phosphate concentrations are established risk factors
      for cardiovascular disease and mortality in chronic kidney disease (CKD).
      Independent associations of other indices of phosphorus metabolism, such as
      phosphorus intake, urinary phosphate excretion, or hormones that regulate these
      systems, like fibroblast growth factor 23 (FGF23), with markers of cardiovascular
      disease in CKD, have been studied in less detail. DESIGN: Cross-sectional study.
      PARTICIPANTS: Seventy-four adult CKD patients with mean creatinine clearance of
      51 +/- 19 mL/minute. OUTCOME: Augmentation index (AI)--a surrogate marker of
      arterial stiffness. RESULTS: Although serum phosphate varied little across
      quartiles of creatinine clearance, average daily phosphorus intake and 24-hour
      urinary phosphate excretion decreased from highest to lowest quartile (by 31% and
      60%, respectively, P for trend <.05). FGF23 was associated with serum phosphate
      (r = 0.24, P = .03) and creatinine clearance (r = -0.4, P = .001), but not with
      dietary phosphorus or 24-hour urinary phosphate excretion (P > .05 for both).
      Older age, higher systolic blood pressure, female gender, and black race were
      independently associated with increased AI. In contrast, there were no
      associations of serum phosphate, dietary phosphorus intake, urinary phosphate
      excretion, or FGF23 with AI in multivariate-adjusted models. CONCLUSIONS: In this
      sample of patients with CKD, established risk factors for arterial stiffness, but
      not mediators of phosphorus metabolism, were associated with increased AI. In
      addition, there were no significant associations between FGF23 and dietary
      phosphorus or urinary phosphate excretion. Future studies are needed to determine
      the main factors associated with elevations in FGF23 in CKD and to further assess
      the association of disordered phosphorus metabolism with subclinical markers of
      vascular disease.

PMID- 22406122
TI  - Malnutrition (subjective global assessment) scores and serum albumin levels, but
      not body mass index values, at initiation of dialysis are independent predictors
      of mortality: a 10-year clinical cohort study.
AB  - OBJECTIVE: To examine the associations between demographic, clinical, lifestyle,
      and nutritional parameters at the start of dialysis and mortality, including the
      combined effects on nutritional parameters, which were seldom investigated in the
      literature. DESIGN: Ten-year retrospective clinical cohort study. SETTING:
      Dialysis unit of a metropolitan tertiary teaching hospital in Sydney, Australia.
      SUBJECTS: Incident dialysis patients (n = 167; hemodialysis, 57.5%; male, 61.7%;
      age, 65.3 +/- 13.6 years; diabetic, 24.5%) who commenced on a planned dialysis
      program. METHODS: Associations were examined between all-cause mortality and
      baseline demographics, including age and gender; clinical and lifestyle
      characteristics, including glomerular filtration rate, smoking habits, presence
      of comorbidities (e.g., coronary artery disease, diabetes mellitus, and
      peripheral vascular disease); and nutritional parameters, including body mass
      index (BMI), serum albumin (s-albumin) levels, and subjective global assessment
      score (SGA). Associations with combination values for malnutrition, s-albumin
      (<3.3 vs. >=3.3 g/dL), and BMI (<26 vs. >=26 kg/m(2)) were also examined.
      RESULTS: Median survival was 54.2 months (interquartile range, 23 to 83), and
      52.1% of patients were malnourished (SGA score B and C) at the start of dialysis.
      Advanced age (classified as >65 years, P < .0001), presence of peripheral
      vascular disease (P < .0001), reduced s-albumin levels (P = .01), and
      malnutrition scores (P = .02) independently predicted mortality. Being overweight
      and obese (BMI: >=26 kg/m(2)) did not show any advantage on survival (P = .73).
      Being malnourished and overweight (or obese) was associated with a 3-fold
      increase in mortality risk (adjusted hazard ratio [HR], 2.96; 95% confidence
      interval [CI], 1.12 to 7.33; P = .02) compared with being well nourished with a
      BMI <26 kg/m(2) (referent). Compared with being well nourished (SGA = A), being
      malnourished with normal or low s-albumin was associated with higher risk (HR,
      2.06; 95% CI, 1.06 to 4.00; P = .03 and HR, 2.86; 95% CI, 1.65 to 4.94; P <
      .0001, respectively). There was no statistical difference between mortality risks
      through any combination of s-albumin and BMI values (P = .54). CONCLUSION:
      Malnutrition and reduced s-albumin levels were found to be independent predictors
      of mortality, whereas being overweight and obese did not show protective effects.

PMID- 22406123
TI  - Differential effect of baseline adiponectin on all-cause mortality in
      hemodialysis patients depending on initial body mass index. Long-term follow-up
      data of 4.5 years.
AB  - OBJECTIVES: We sought to investigate the interaction of adiponectin levels and
      body mass index (BMI) for predicting all-cause mortality in a cohort of
      hemodialysis (HD) patients. DESIGN: Longitudinal, observational cohort study.
      SETTING: HD unit. SUBJECTS: Sixty patients (mean age: 64 +/- 13 years, 39 men)
      with end-stage renal disease on maintenance HD followed up for 4.5 years
      represented the prospective study cohort. INTERVENTION: Associations between
      baseline plasma adiponectin levels and initial BMI with all-cause mortality were
      assessed taking into account the assumption of nonlinear correlations. The
      association between adiponectin, BMI, and serum levels of interleukin-10 (IL-10)
      and interleukin-6 (IL-6) with survival was determined cross-sectionally. MAIN
      OUTCOME MEASURE: All-cause mortality. RESULTS: Nonlinear survival modeling showed
      that there was a U-shaped association of BMI with all-cause mortality, whereas
      there was an inverse U-shaped association for plasma adiponectin levels. Using a
      BMI of 24 kg/m(2) as a cutoff, an interaction effect of BMI on the association
      between adiponectin and mortality was observed (P = .045). In participants with
      BMI >= 24 kg/m(2), each 15 MUg/mL increase in plasma adiponectin levels was
      associated with a decreased hazard of death (hazard ratio: 0.57, 95% CI: 0.32 to
      0.99) in unadjusted analysis. In HD patients with BMI < 24 kg/m(2), no
      significant association was observed between adiponectin and mortality (P =
      .989). Cross-sectional analysis showed that in the subgroup of patients in whom
      the protective effect of adiponectin was observed (BMI >= 24 kg/m(2)), a positive
      linear association existed between adiponectin and IL-10 levels (r = 0.345, P =
      .027) as well as a negative association with IL-6 levels (r = -0.322, P = .040).
      No association was observed in patients with BMI < 24 kg/m(2), neither with IL-10
      nor with IL-6. CONCLUSIONS: Obesity possibly modifies the effect of adiponectin
      on all-cause mortality in HD patients, thus explaining the published conflicting
      results in recent literature regarding the association of plasma adiponectin
      levels and mortality in chronic kidney disease patients.

PMID- 22406124
TI  - Assessment of body composition using dry mass index and ratio of total body water
      to estimated volume based on bioelectrical impedance analysis in chronic kidney
      disease patients.
AB  - OBJECTIVE: Body mass index (BMI) is commonly used for assessment of nutritional
      status. However, changes in BMI in chronic kidney disease (CKD) patients are
      affected not only by muscle and fat but also by fluid volume. The ratio of
      extracellular water (ECW(BIA)) to total body water (TBW(BIA)) in multifrequency
      bioelectrical impedance analysis is commonly used for assessing abnormal fluid
      status. This study reexamines ECW(BIA)/TBW(BIA) and evaluates the reliability of
      TBW(BIA)/TBW(watson) and dry mass index (DMI) in the assessment of fluid and
      nutritional status. DESIGN, SETTING, AND SUBJECTS: TBW(BIA), intracellular water
      (ICW(BIA)), and ECW(BIA) were measured in 45 randomly selected CKD patients.
      Participants were surveyed for age, gender, BMI, blood pressure, serum albumin,
      estimated glomerular filtration rate, and proteinuria. DMI was calculated by the
      formula ([weight--TBW(BIA)]/height(2)) and TBW(BIA)/TBW(watson) using an
      anthropometric formula (Watson). Fluid and nutritional status were assessed using
      ECW(BIA)/TBW(BIA), TBW(BIA)/TBW(watson), and DMI. RESULTS: TBW(BIA)/TBW(watson)
      positively correlated with weight, BMI, and diastolic blood pressure and
      negatively correlated with age and serum albumin level. In contrast,
      ECW(BIA)/TBW(BIA) correlated with ICW deficit, aging, and body weight loss. On
      the basis of DMI and TBW(BIA)/TBW(watson), participants were categorized as
      follows: 1 obese patient with hypovolemia and 2 with euvolemia; 17 overweight
      patients with hypovolemia (n = 6), euvolemia (n = 8), or hypervolemia (n = 3); 24
      patients of optimal weight with hypovolemia (n = 10), euvolemia (n = 9), or
      hypervolemia (n = 5); and 1 underweight patient with euvolemia. CONCLUSIONS: A
      combination of DMI, BMI, and TBW(BIA)/TBW(watson) makes it possible to include
      assessment of fluid volume to the physique index. In addition, ECW(BIA)/TBW(BIA)
      is not a reliable marker of edematous state in CKD patients.

PMID- 22406125
TI  - De novo biosynthesis of starch chains without a primer and the mechanism for its
      biosynthesis by potato starch-synthase.
AB  - The starch-synthase enzymes used in this study were the second acetone
      precipitate and Fractions 21 and 23, Table 1, [Mukerjea, Ru.; Falconer, D. J.;
      Yoon, S.-H.; Robyt, J. F. Carbohydr. Res. 2010, 345, 1555-1563]. Fractions 21 and
      23 had high specific activities of 544 and 944 International Units/mg,
      respectively. When the enzymes and buffer and substrate were treated with
      immobilized alpha-amylase and glucoamylase for 30 min, they all had the same
      activity, before and after treatment, indicating that the enzymes were free of
      putative primers and synthesized amylose chains de novo, without the addition of
      primers. Starch-synthase was immobilized and reacted with ADP-[(14)C]Glc; the
      immobilized enzyme was removed, washed and treated at pH 2 and 50  degrees C for
      30 min, giving the release of (14)C-D-glucopyranose and (14)C-amylose, showing
      that during catalysis they were covalently attached to the enzyme active-site.
      Pulse and chase reactions of starch-synthase with ADP-[(14)C]Glc and ADPGlc,
      respectively, followed by reduction and acid hydrolysis of the starch-chain
      product, gave (14)C-D-glucitol from the pulse reaction and a significant decrease
      of (14)C-D-glucitol from the chase reaction, showing that the addition of D
      glucose from ADPGlc was to the reducing-ends of the growing amylose chains.
      Reactions of four different concentrations of starch-synthase, with constant
      ADPGlc concentration and temperature, gave four amylose chains, each with
      different number average molecular weights that were inversely proportional to
      the concentration of the enzyme, indicating that the synthesis was processive.
      From the results, a two catalytic-site, insertion mechanism is proposed for the
      biosynthesis of starch chains.

PMID- 22406126
TI  - Long term effects of the daily wear of senofilcon a silicone hydrogel contact
      lenses on eyelid tissues.
AB  - PURPOSE: Eyelid changes have been reported with silicone hydrogel contact lenses.
      It is hypothesized that those changes are associated with the mechanical
      interaction between the contact lens front surface and eyelid tissues and, are
      specific to contact lens type rather than a general effect of the lens category.
      The purpose of this study was to assess the effect of refitting into a silicone
      hydrogel on a daily wear basis to current contact lens wearers, lapsed wearers
      and neophytes on eyelid physiology. METHODS: The investigation was a 2-year
      prospective investigation of ACUVUE(r) OASYS(r) with HYDRACLEAR(r) Plus
      (senofilcon A) used with care systems, representative of current practice.
      RESULTS: 90 subjects were enrolled of whom 64 subjects completed the
      investigation. The results obtained were as follows: CONCLUSIONS: The results of
      the study demonstrated that senofilcon A, worn on a daily wear basis and replaced
      every 2 weeks, did not produce any eyelid tissue changes in previous non-contact
      lens wearers at baseline and revealed no change or a slight improvement of the
      eyelid tissues of established contact lens wearers.

PMID- 22406127
TI  - [High-fat diets and body composition over two generations. An experimental
      study].
AB  - INTRODUCTION AND OBJECTIVE: Despite recent findings reported on the nutritional
      factors that induce epigenetic changes, little information is available at early
      ages. This study analyzed in an experimental model, over two generations,
      potential changes in body composition and potential expression of epigenetic
      changes as the result of the intake of isoenergetic diets with different fat
      levels. MATERIALS AND METHODS: At weaning, Wistar female rats were divided into
      two groups that were fed either a control diet (fat=7% w/w) or a high-fat diet
      (15% w/w). Rats were mated at 70 days (M(1)) and their pups (P(1)) were the first
      generation; P(1) rats were mated at 70 days (M(2)) and their pups (P(2))
      represented the second generation. At weaning, mothers and pups (M(1), M(2) and
      P(1), P(2)) were measured body weight (W) and composition (% body fat, %BF), and
      total skeleton bone mineral content (BMC), expressed as %BMC, using chemical and
      DXA methods respectively. RESULTS: At weaning, high-fat diet groups M(2) and P(2)
      showed significant increases in W and %BF (p<0.05); increased %BF values were
      already found in the M(1) and P(1) groups (p<0.001). By contrast, %BMC
      significantly decreased in M(2) and P(2) rats (p<0.001). CONCLUSION: This study
      demonstrates the need to review certain eating habits to avoid perpetuation of
      unhealthy patterns generation after generation.

PMID- 22406128
TI  - Induction of protective immunity in chickens immunized with plant-made chimeric
      Bamboo mosaic virus particles expressing very virulent Infectious bursal disease
      virus antigen.
AB  - Very virulent Infectious bursal disease virus (vvIBDV) causes a highly contagious
      disease in young chickens and leads to significant economic loss in the poultry
      industry. Effective new vaccines are urgently needed. Autonomously replicating
      plant virus-based vector provides attractive means for producing chimeric virus
      particles (CVPs) in plants that can be developed into vaccines. In this study, we
      demonstrate the potential for vaccine development of Bamboo mosaic virus (BaMV)
      epitope-presentation system, where the antigen from vvIBDV VP2 was fused to the N
      terminus of BaMV coat protein. Accordingly, an infections plasmid, pBIBD2, was
      constructed. Inoculation of the recombinant BaMV clone pBIBD2 enabled the
      generation of chimeric virus, BIBD2, and stable expression of IBDV VP2 antigen on
      its coat protein. After intramuscular immunization with BIBD2 CVPs, chickens
      produced antibodies against IBDV and were protected from vvIBDV (V263/TW strain)
      challenges. These results corroborate the feasibility of BaMV-based CVP platform
      in plants for the development and production of vaccines against IBDV.

PMID- 22406129
TI  - Unique variations of Epstein-Barr virus-encoded BARF1 gene in nasopharyngeal
      carcinoma biopsies.
AB  - The Epstein-Barr virus (EBV) BamHI-A rightward frame 1 (BARF1) gene is frequently
      expressed in EBV-associated epithelial malignancies and involves in oncogenicity
      and immunomodulation. To characterize the variations of BARF1 gene in different
      populations, the sequences of BARF1 gene in Northern Chinese nasopharyngeal
      carcinoma (NPC), EBV-associated gastric carcinoma (EBVaGC) and healthy donors
      were analyzed. The correlation of BARF1 variation with polymorphisms of BamHI F
      fragment (type F and f variants) and EBV-coded viral interleukin-10 (vIL-10) gene
      (B95-8 and SPM patterns) was also explored. Two major subtypes of BARF1 gene,
      designated as B95-8 and V29A, were identified. B95-8 subtype had identical amino
      acid sequence to B95-8 and was the dominant subtype among the EBV isolates from
      Northern China. V29A subtype, with one consistent amino acid change at residue 29
      (V->A) and several nucleotide changes, showed higher frequency in NPC cases
      (25.3%, 20/79) than in EBVaGC cases (0/45) or healthy donors (4.3%, 2/46) (NPC
      vs. EBVaGC: P=0.0001; NPC vs. healthy donor: P=0.004). A preferential linkage
      between BamHI F and BARF1/vIL-10 polymorphisms was found. Type f isolates was
      specially correlated with the V29A/SPM genotype in NPC isolates and type
      f/V29A/SPM was preferentially found in NPC. BARF1/c-fms homology domain,
      transforming domain and cytotoxic T lymphocyte (CTL) epitopes of BARF1 were
      highly conserved in most isolates, suggesting the important role of BARF1 in
      virus infection and the potential usefulness in EBV-targeting immunotherapy of
      EBV-associated tumors. The relatively higher prevalence of type f/V29A/SPM
      strains in NPC may also suggest the association between these variations in
      multiple viral genes and NPC.

PMID- 22406130
TI  - A reverse genetic study of the adaptation of human enterovirus 71 to growth in
      Chinese hamster ovary cell cultures.
AB  - We selected Chinese hamster ovary (CHO) cell-adapted strains of human enterovirus
      71 (HEV71) belonging to sub-genogroups B5 (HEV71-B5) and C2 (HEV71-C2) by serial
      passage in CHO cells at a high multiplicity of infection. During the course of
      CHO cell passage, virus growth improved significantly, with increasing virus
      titres and the presence of cytopathic effect observed. A study of virus growth
      kinetics revealed that the CHO cell-adapted strains of HEV71-B5 (CHO-B5) and
      HEV71-C2 (CHO-C2) grew efficiently in CHO cells with maximum titres >100-fold
      higher than unadapted parental virus. Both CHO-B5 and CHO-C2 harboured single
      amino acid mutations within the VP2 capsid protein gene. CHO-B5 has an amino acid
      substitution of K(149)->I in VP2 and CHO-C2 has an amino acid substitution of
      K(149)->M in VP2. An isolate of sub-genogroup C4 (HEV71-C4) failed to adapt to
      CHO cells during serial passage. Infectious cDNA clone-derived populations of
      HEV71-C4 containing the mutations K(149)->I or K(149)->M in VP2 were generated by
      site-directed mutagenesis. Both mutations resulted in the ability of the virus to
      replicate efficiently in CHO cells, indicating that amino acid position 149 in
      VP2 is critical for the adaptation of HEV71 to growth in CHO cells.

PMID- 22406131
TI  - ZnO thin film with nanorod arrays applied to fluid sensor.
AB  - A ZnO guiding layer with nanorod arrays grown on a 90 degrees -rotated ST-cut (42
      degrees 45) quartz substrate was used to fabricate a Love wave fluid sensor. ZnO
      nanorod arrays synthesized on the guiding layer enhance the sensitivity of the
      flow rate. ZnO thin films were deposited by radio frequency magnetron sputtering
      and ZnO nanorod arrays were then synthesized on the thin films via the
      hydrothermal method. The crystalline structure and surface morphology of ZnO thin
      films and nanorod arrays were examined by X-ray diffraction and scanning electron
      microscopy. The effects of the thickness of ZnO thin film and the surface
      morphology of ZnO nanorod arrays on the sensitivity of flow rate were
      investigated. A linear response between flow rate and the return loss of the
      sensor with one-port resonator type can be obtained by adjusting the thickness of
      ZnO thin film and the length of nanorod arrays.

PMID- 22406132
TI  - Nonlinear response to ultrasound of encapsulated microbubbles.
AB  - The acoustic backscatter of encapsulated gas-filled microbubbles immersed in a
      weak compressible liquid and irradiated by ultrasound fields of moderate to high
      pressure amplitudes is investigated theoretically. The problem is formulated by
      considering, for the viscoelastic shell of finite thickness, an isotropic
      hyperelastic neo-Hookean model for the elastic contribution in addition to a
      Newtonian viscous component. First and second harmonic scattering cross-sections
      have been evaluated and the quantitative influence of the driving pressure
      amplitude on the harmonic resonance frequencies for different initial equilibrium
      bubble sizes and for different encapsulating physical properties has been
      determined. Conditions for optimal second harmonic imaging have been also
      investigated and some regions in the parameters space where the second harmonic
      intensity is dominant over the fundamental have been identified. Results have
      been obtained for albumin, lipid and polymer encapsulating shells, respectively.

PMID- 22406133
TI  - Bringing prevention in geriatrics: evidences from cardiovascular medicine
      supporting the new challenge.
AB  - Aging is a dynamic and systemic process, with high inter-individual
      heterogeneity, likely partially adaptive. Cardiovascular disease and hypertension
      are among the leading conditions causing disabilities in older subjects. If, in
      accordance with most recent definition, prevention is any intervention before the
      patient receives a diagnosis, prevention is possible at any age. Additionally,
      disability and CV disease in the elderly may be prevented by targeting factors
      underlying and modulating the arterial aging process. Cross-talk between arterial
      and brain aging will be discussed in this context as a paradigmatic clinical
      model fostering prevention in older subjects.

PMID- 22406134
TI  - Calorie restriction in mice overexpressing UCP3: evidence that prior
      mitochondrial uncoupling alters response.
AB  - Calorie restriction (CR) without malnutrition is the only intervention to
      consistently increase lifespan in all species tested, and lower age-related
      pathologies in mammals including humans. It has been suggested that uncoupling of
      mitochondrial oxidative phosphorylation, using chemical uncouplers, mimics CR,
      and that overlapping mechanisms underlie the phenotypic changes induced by
      uncoupling and CR. We aimed to critically assess this using a unique mouse model
      of skeletal muscle-targeted UCP3-induced uncoupling (UCP3Tg), and focused our
      studies mainly on skeletal muscle mitochondria. Compared to ad libitum fed Wt
      mice, skeletal muscle mitochondria from ad libitum fed UCP3Tg mice showed higher
      basal uncoupling and lower H(2)O(2) emission, with unchanged maximal oxidative
      phosphorylation, and mitochondrial content. UCP3Tg CR mice showed some tendency
      for differential adaptation to CR, with lowered H(+) leak conductance and
      evidence for higher H(2)O(2) emission from skeletal muscle mitochondria following
      2 weeks CR, and failure to lower H(2)O(2) emission after 1 month CR. Differential
      adaptation was also apparent at the whole body level: while UCP3Tg CR mice lost
      as much weight as Wt CR mice, the proportion of muscle lost was higher in UCP3Tg
      mice. However, a striking outcome of our studies was the absence of change with
      CR in many of the parameters of mitochondrial function and content that we
      measured in mice of either genotype. Overall, our study raises the question of
      whether CR can consistently modify skeletal muscle mitochondria; alterations with
      CR may only be apparent under certain conditions such as during the 2 wk CR
      intervention in the UCP3Tg mice.

PMID- 22406135
TI  - Lines and circles: pictorial review of cross-sectional imaging of active bleeding
      and pseudoaneurysm in the abdomen and pelvis.

PMID- 22406136
TI  - Dose-length product to effective dose conversion factors for common computed
      tomography examinations based on Canadian clinical experience.

PMID- 22406137
TI  - Consumer inhalation exposure to formaldehyde from the use of personal care
      products/cosmetics.
AB  - We measured consumer exposure to formaldehyde (FA) from personal care products
      (PCP) containing FA-releasing preservatives. Six study subjects applied facial
      moisturiser, foundation, shower gel, shampoo, deodorant, hair conditioner, hair
      styling gel or body lotion at the 90th percentile amount of EU PCP consumer use.
      FA air concentrations were measured in the empty room, in the presence of study
      subjects prior to PCP use, and for one hour (breathing zone, area monitoring)
      after PCP use. The mean FA air concentration in the empty bathroom was 1.32 +/-
      0.67 MUg/m3, in the presence of subjects it was 2.33 +/- 0.86 MUg/m3). Except for
      body lotion and hair conditioner (6.2 +/- 0.1.9 or 4.5 +/- 0.1.5 MUg/m3,
      respectively), mean 1-h FA air concentrations after PCP use were similar to
      background. Peak FA air concentrations, ranging from baseline values (2.2 MUg/m3;
      shower gel) to 11.5 MUg/m3 (body lotion), occurred during 0-5 to 5-10 min after
      PCP use. Despite of exaggerated exposure conditions, FA air levels were a
      fraction of those considered to be safe (120 MUg/m3), occurring in indoor air (22
      124 MUg/m3) or expired human breath (1.4-87 MUg/m3). Overall, our data yielded
      evidence that inhalation of FA from the use of PCP containing FA-releasers poses
      no risk to human health.

PMID- 22406138
TI  - Social behavior, chemical communication, and adult neurogenesis: studies of scent
      mark function in Podarcis wall lizards.
AB  - Lacertid lizards have been hailed as a model system for the study of reptilian
      chemical communication. However, results obtained with the genus Podarcis, a
      diverse group of wall lizards with complex systematics, challenge emerging
      paradigms and caution against hasty generalizations. Here we review the available
      evidence on the role of chemical stimuli in male-female and male-male
      interactions in Iberian Podarcis. Males of several species can discriminate
      between chemicals left on substrates by females of their own or a different
      species, suggesting that differences in female chemical cues may underlie species
      recognition in this group. Females, on the other hand, do not respond
      differentially to conspecific and congeneric male scent marks. Males of Podarcis
      liolepis use scent marks to recognize rivals individually, evaluate their
      competitive ability (i.e., body size), and assess the threat posed by each
      individual rival neighbor. In contrast, females do not exhibit a preference for
      territories scent marked by larger (i.e., more competitive) males, which suggests
      a limited role for male scent marks in pre-copulatory mate choice. This
      behavioral sex difference is consistent with detailed neuro-ethological evidence
      showing that chemosensory brain areas in P. liolepis are sexually dimorphic. The
      accessory olfactory bulbs are larger (both in absolute and relative terms) in
      males than in females, probably as a result of sex-specific rates of adult
      neurogenesis. In both sexes, cell proliferation undergoes seasonal cycles that
      may have evolved to satisfy increased chemosensory demands at particular times of
      the year. Overall, and against recent generalizations, these results suggest that
      male scent marks have been shaped mainly by strong intrasexual selection.

PMID- 22406139
TI  - HJURP uses distinct CENP-A surfaces to recognize and to stabilize CENP-A/histone
      H4 for centromere assembly.
AB  - Centromeres are defined by the presence of chromatin containing the histone H3
      variant, CENP-A, whose assembly into nucleosomes requires the chromatin assembly
      factor HJURP. We find that whereas surface-exposed residues in the CENP-A
      targeting domain (CATD) are the primary sequence determinants for HJURP
      recognition, buried CATD residues that generate rigidity with H4 are also
      required for efficient incorporation into centromeres. HJURP contact points
      adjacent to the CATD on the CENP-A surface are not used for binding specificity
      but rather to transmit stability broadly throughout the histone fold domains of
      both CENP-A and H4. Furthermore, an intact CENP-A/CENP-A interface is a
      requirement for stable chromatin incorporation immediately upon HJURP-mediated
      assembly. These data offer insight into the mechanism by which HJURP
      discriminates CENP-A from bulk histone complexes and chaperones CENP-A/H4 for a
      substantial portion of the cell cycle prior to mediating chromatin assembly at
      the centromere.

PMID- 22406140
TI  - Spindle position in symmetric cell divisions during epiboly is controlled by
      opposing and dynamic apicobasal forces.
AB  - Orientation of cell division is a vital aspect of tissue morphogenesis and
      growth. Asymmetric divisions generate cell fate diversity and epithelial
      stratification, whereas symmetric divisions contribute to tissue growth,
      spreading, and elongation. Here, we describe a mechanism for positioning the
      spindle in symmetric cell divisions of an embryonic epithelium. We show that
      during the early stages of epiboly, spindles in the epithelium display dynamic
      behavior within the plane of the epithelium but are kept firmly within this plane
      to give a symmetric division. This dynamic stability relies on balancing
      counteracting forces: an apically directed force exerted by F-actin/myosin-2 via
      active cortical flow and a basally directed force mediated by microtubules and
      myosin-10. When both forces are disrupted, spindle orientation deviates from the
      epithelial plane, and epithelial surface is reduced. We propose that this dynamic
      mechanism maintains symmetric divisions while allowing the quick adjustment of
      division plane to facilitate even tissue spreading.

PMID- 22406141
TI  - Molecular characterization of the NSP4 gene of human group A rotavirus strains
      circulating in Tunisia from 2006 to 2008.
AB  - Non-structural protein 4 (NSP4), encoded by group A rotavirus (RVA) genome
      segment 10, is a multifunctional protein and the first recognized virus-encoded
      enterotoxin. Recently, a new classification system for RVAs was proposed and a
      total of 14 NSP4 genotypes (E1-E14) are currently described. The most common NSP4
      genotypes in humans are Wa-like E1 and DS-1-like E2. This report represents the
      first investigation on the genetic diversity of RVA NSP4 genes in Tunisia from
      2006 to 2008. In the present study, the NSP4-encoding genes of human RVA strains
      with different G/P-genotype combinations were analyzed. NSP4 genes of 261 RVA
      positive fecal samples were analyzed using a semi-nested reverse transcriptase
      polymerase chain reaction and in addition the NSP4 gene of 46 representative RVA
      strains were sequenced. Phylogenetic analysis of the Tunisian NSP4 nucleotide
      sequences revealed the presence of two NSP4 genotypes. Genotype E1 was found to
      be associated with G1P[8], G3P[6], G3P[8], G4P[6] and G4P[8], whereas genotype E2
      was associated with G2P[4], G2P[6] and G6P[9] samples. These results support the
      hypothesis that P[8] carrying RVA strains usually possess the E1 genotype,
      whereas P[4] carrying RVA strains usually possess the E2 genotype. P[6] carrying
      strains were found with both E1 and E2. The unusual G6P[9] strains possessed a E2
      genotype with a possible animal origin. These results underline the need for
      further investigations to assess the validity of NSP4 as a suitable target for
      epidemiologic surveillance of RVA infections and vaccine development.

PMID- 22406142
TI  - Membrane effects of lysozyme amyloid fibrils.
AB  - The influence of mature lysozyme fibrils on the structural and physical
      properties of model membranes composed of phosphatidylcholine (PC) and its
      mixtures with cardiolipin (CL) (10 mol%) and cholesterol (Chol) (30 mol%) was
      studied using fluorescent probes DPH, pyrene, Laurdan and MBA. Analysis of pyrene
      fluorescence spectra along with the measurements of DPH fluorescence anisotropy
      revealed that the structure of hydrocarbon chains region of lipid bilayer is not
      affected by the fibrillar aggregates of lysozyme. In contrast, probing the
      membrane effects by Laurdan and MBA showed the rise of both the generalized
      polarization of Laurdan and the MBA fluorescence anisotropy, suggesting that
      amyloid protein induces reduction of bilayer hydration and increase of lipid
      packing in the interfacial region of model membranes.

PMID- 22406143
TI  - Ethanol infusion in the vein of Marshall facilitates mitral isthmus ablation.
AB  - BACKGROUND: Treatment of perimitral flutter (PMF) requires bidirectional mitral
      isthmus (MI) block, which can be difficult with radiofrequency ablation (RFA).
      The vein of Marshall (VOM) is located within the MI. OBJECTIVE: To test whether
      VOM ethanol infusion could help achieve MI block. METHODS: Perimitral conduction
      was studied in patients undergoing ablation of atrial fibrillation. Group 1
      included 50 patients with a previous atrial fibrillation ablation undergoing
      repeat ablation, 30 of whom had had MI ablation. Spontaneous (8 of 50) or
      inducible PMF (21 of 50) was confirmed by activation mapping. Group 2 included 21
      patients undergoing de novo VOM ethanol infusion. The VOM was cannulated with a
      quadripolar catheter for pacing and with an angioplasty balloon to deliver up to
      four 1-mL infusions of 98% ethanol. Voltage maps were created before and after
      VOM ethanol infusion. Bidirectional MI block was verified by differential pacing.
      RFA times required to achieve it were assessed. RESULTS: In group 1, VOM ethanol
      infusion acutely terminated PMF in 5 of 29 patients. RFA needed to achieve
      bidirectional MI block was 2.2 +/- 1.6 minutes. Presence of PMF or previous MI
      ablation did not affect RFA times. In group 2, RFA needed to achieve
      bidirectional MI block was 2.0 +/- 1.6 minutes (P = NS). Five patients had
      bidirectional MI block achieved solely by VOM ethanol infusion without RFA. In
      both groups, ablation after VOM ethanol infusion was required in the annular
      aspect of the MI. There were no acute complications. CONCLUSION: VOM ethanol
      infusion is useful in the treatment of PMF and assists in reliably achieving
      bidirectional MI block.

PMID- 22406145
TI  - Relationship between the CHADS(2) score and risk of very late recurrences after
      catheter ablation of paroxysmal atrial fibrillation.
AB  - BACKGROUND: Catheter ablation of paroxysmal atrial fibrillation has been
      performed for more than 10 years. However, data about the long-term results were
      limited. OBJECTIVES: To evaluate the long-tem efficacy following paroxysmal
      atrial fibrillation ablation and to investigate whether there were different
      patterns of recurrences in patients with different CHADS(2) scores. METHODS: A
      total of 238 patients with paroxysmal atrial fibrillation who received a catheter
      ablation from 2004 to 2007 were enrolled. Free of recurrence was defined as the
      absence of atrial arrhythmias without using any antiarrhythmic agents after
      ablation. RESULTS: There were 121 patients (50.8%) suffering from recurrences
      after the first ablation procedure during a median follow-up period of 5 years.
      The CHADS(2) score and left atrial diameter were significant predictors of
      recurrences in the multivariate analysis. Different patterns of recurrence were
      observed in different groups of patients categorized on the base of CHADS(2)
      score. Among patients with a CHADS(2) score of >=3 without recurrences at 2 years
      postablation, 63.6% experienced episodes of arrhythmias during the subsequent
      follow-up period. In contrast, in patients with a CHADS(2) score of 0 without
      recurrences at 2 years postablation, the future recurrence rate was only 2.7%.
      CONCLUSIONS: After a successful ablation, recurrences may continue to occur
      without reaching a plateau during the long-term follow-up, especially in patients
      with a high CHADS(2) score. The optimal follow-up strategy may differ and should
      be individualized for patients with different scores.

PMID- 22406144
TI  - Remodeling of mechanical junctions and of microtubule-associated proteins
      accompany cardiac connexin43 lateralization.
AB  - BACKGROUND: Desmosomes and adherens junctions provide mechanical continuity
      between cardiac cells, whereas gap junctions allow for cell-cell
      electrical/metabolic coupling. These structures reside at the cardiac
      intercalated disc (ID). Also at the ID is the voltage-gated sodium channel (VGSC)
      complex. Functional interactions between desmosomes, gap junctions, and VGSC have
      been demonstrated. Separate studies show, under various conditions, reduced
      presence of gap junctions at the ID and redistribution of connexin43 (Cx43) to
      plaques oriented parallel to fiber direction (gap junction "lateralization").
      OBJECTIVE: To determine the mechanisms of Cx43 lateralization, and the fate of
      desmosomal and sodium channel molecules in the setting of Cx43 remodeling.
      METHODS: Adult sheep were subjected to right ventricular pressure overload
      (pulmonary hypertension). Tissue was analyzed by quantitative confocal microscopy
      and by transmission electron microscopy. Ionic currents were measured using
      conventional patch clamp. RESULT: Quantitative confocal microscopy demonstrated
      lateralization of immunoreactive junctional molecules. Desmosomes and gap
      junctions in lateral membranes were demonstrable by electron microscopy.
      Cx43/desmosomal remodeling was accompanied by lateralization of 2 microtubule
      associated proteins relevant for Cx43 trafficking: EB1 and kinesin protein Kif5b.
      In contrast, molecules of the VGSC failed to reorganize in plaques discernable by
      confocal microscopy. Patch-clamp studies demonstrated change in amplitude and
      kinetics of sodium current and a small reduction in electrical coupling between
      cells. CONCLUSIONS: Cx43 lateralization is part of a complex remodeling that
      includes mechanical and gap junctions but may exclude components of the VGSC. We
      speculate that lateralization results from redirectionality of microtubule
      mediated forward trafficking. Remodeling of junctional complexes may preserve
      electrical synchrony under conditions that disrupt ID integrity.

PMID- 22406146
TI  - Pacemap of delta wave for successful ablation of traumatized atrioventricular
      accessory pathway.

PMID- 22406147
TI  - A new therapeutic approach for postoperative systemic inflammation: effectiveness
      of epicardial ganglionated plexus stimulation.

PMID- 22406148
TI  - Fish oil for atrial fibrillation prevention: can we intervene soon enough to make
      a difference?

PMID- 22406149
TI  - Early repolarization pattern is associated with ventricular fibrillation in
      patients with acute myocardial infarction.
AB  - BACKGROUND: For years early repolarization (ER) has been considered as a benign
      electrocardiographic finding. However, recent reports show that ER is associated
      with a higher incidence of ventricular fibrillation (VF) and sudden cardiac death
      in patients without structural heart disease. Sporadic case studies have pointed
      out that ER might be related to an adverse outcome in patients with stable
      coronary artery disease. OBJECTIVE: To evaluate the incidence of ER in patients
      with acute myocardial infarction complicated by VF. METHODS: The study population
      consisted of 60 patients (80% men; mean age 61.8 +/- 13.1 years) with acute
      myocardial infarction. Thirty consecutive patients (80% men; mean age 63.3 +/- 12
      years) admitted to our hospital had documented VF during myocardial infarction
      and were successfully resuscitated before hospital admission. A matched control
      group consisted of 30 patients (80% men; mean age 60.2 +/- 14.2 years) with
      myocardial infarction without ventricular tachyarrhythmias. Twelve-lead
      electrocardiograms were analyzed for ER defined as J-point elevation >= 0.1 mV
      and "notching" and "slurring" of the terminal part of the QRS complex in at least
      2 lateral or inferior leads. RESULTS: The ER pattern was observed in 18 of the 60
      patients with acute myocardial infarction. Mean elevation of the J point was
      0.151 +/- 0.46 mV. Notching of the J wave was observed in 14 of the 18 patients
      and slurring in 4 of the 18 patients. ER was more common in patients with
      myocardial infarction complicated by VF than in patients with myocardial
      infarction without ventricular tachyarrhythmias (47% vs 13%; P = .005). There
      have been no statistical differences in the distribution of ER in the 12-lead
      electrocardiogram (inferior 39% vs lateral 33% vs inferolateral 28%; P >.05).
      CONCLUSION: Early repolarization pattern seems to be associated with ventricular
      tachyarrhythmias in the setting of acute myocardial infarction.

PMID- 22406150
TI  - Synthesis and properties of cationic 2'-O-[N-(4-aminobutyl)carbamoyl] modified
      oligonucleotides.
AB  - 2'-O-[N-(4-Aminobutylcarbamoyl)]uridine (U(abcm)) was synthesized and
      incorporated into oligonucleotides. The oligonucleotides incorporating U(abcm)
      formed more stable duplexes with their complementary and mismatched RNAs than
      those containing 2'-O-carbamoyluridine (U(cm)). The stability of duplex with a
      U(abcm)-rG base pair showed higher thermostability than the duplex having
      unmodified U-rG base pair. The U(abcm) residue showed enhanced resistance to
      snake venome phosphodiesterase.

PMID- 22406151
TI  - Design and synthesis of orally available MEK inhibitors with potent in vivo
      antitumor efficacy.
AB  - The structure-based design, synthesis, and biological evaluation of two novel
      series of potent and selective MEK kinase inhibitors are described herein. The
      elaboration of a lead pyrrole derivative to a bicyclic dihydroindolone core
      provided compounds with high potency and good drug-like pharmaceutical
      properties. Further scaffold modification afforded a series of
      dihydroindolizinone inhibitors, including an orally available advanced
      preclinical MEK inhibitor with potent in vivo antitumor efficacy.

PMID- 22406152
TI  - Structure aided design of chimeric antibiotics.
AB  - The rise of antibiotic resistance is of great clinical concern. One approach to
      reducing the development of resistance is to co-administer two or more
      antibiotics with different modes of action. However, it can be difficult to
      control the distribution and pharmacokinetics of two drugs to ensure both
      concentrations remain within the range of therapeutic efficacy whilst avoiding
      adverse effects. Hybrid drugs, where two drugs are linked together with a
      flexible linker, have been explored, but the resultant large, flexible molecules
      can have poor bioavailability. We have developed a chimeric approach using click
      chemistry where the pharmacophores of two drugs are overlapped into a single
      smaller, more drug-like molecule. Design and selection of compounds were assisted
      by in silico structural docking. We prepared a series of compounds that include
      candidates showing activity against the targets of both trimethoprim;
      dihydrofolate reductase, and ciprofloxacin; DNA gyrase and topoisomerase IV. The
      resultant triazole containing molecules show modest, but broad spectrum
      activities against drug sensitive and resistant Gram-negative and Gram-positive
      bacteria, with no observable cytotoxicity.

PMID- 22406153
TI  - Facile synthesis of triterpenoid saponins bearing beta-Glu/Gal-(1->3)-beta-GluA
      methyl ester and their cytotoxic activities.
AB  - Convenient synthetic strategy toward spinasaponin A methyl ester 1 and
      calenduloside G methyl ester 2, two natural oleanane-type triterpenoid saponins
      bearing an unique beta-D-glucosyl/galactosyl-(1->3)-beta-D-glucuronic acid methyl
      ester disaccharide moiety, was established. Based on this facile approach, four
      structurally modified congeners 3-6 with ursolic acid and glycyrrhetinic acid as
      aglycones were efficiently synthesized. MTT assay revealed the cytotoxicities
      against cancer cells of the synthesized saponins were varied with the change of
      aglycones and sugar units. Saponin 2 possessing the most potent cytotoxic effects
      could induce apoptosis of MCF-7 cells, which was detected by confocal micrographs
      using DAPI staining and flow cytometry using Annexin V and PI double staining.
      Furthermore, 2-induced apoptosis in MCF-7 cells was associated with ROS
      generation and loss of the mitochondria membrane potential (Deltapsi(m)).

PMID- 22406154
TI  - Characteristics of non-clustered tuberculosis in a low burden country.
AB  - Molecular genotyping studies often focus on clustered tuberculosis and recent
      transmission. Less attention has been paid to non-clustered tuberculosis.
      However, non-clustered cases also contribute significantly to the tuberculosis
      burden, especially in low-incidence countries. The objective of this study is to
      characterize non-clustered tuberculosis cases in Denmark and point out potential
      implications for tuberculosis control. The study is based on nationwide IS6110
      RFLP genotyping of tuberculosis cases from 1992 through 2004, corresponding to
      98% of culture verified cases. Of 3988 cases, 45% were non-clustered. Both Danes
      and immigrants had a peak incidence of non-clustered tuberculosis at older ages,
      80-89 years (4.3 cases/10(5) population/year) and 60-69 years (28.8 cases/10(5)
      population/year), respectively. In addition, immigrants had a peak at 20-29 years
      (43.2 cases/10(5) inhabitants/year). In Danes, the incidence of non-clustered
      tuberculosis decreased during the study period and was predominantly found in
      elderly persons, presumably reactivating infection acquired during 1910-40, when
      tuberculosis incidence was high. In immigrants, the incidence was high at all
      ages, presumably reflecting reactivation of imported infections. In the future,
      the number of non-clustered tuberculosis cases will decrease, as older Danes die,
      and as time since primary infection increases for immigrants residing in Denmark.
      TB control should include focus on non-clustered cases.

PMID- 22406155
TI  - Anti-phospholipid antibody levels as biomarker for monitoring tuberculosis
      treatment response.
AB  - Standard methods to monitor tuberculosis (TB) treatment response rely on sputum
      microscopy and culture conversion. Alternatives to these methods are needed for
      those patients whose sputum tests are smear or culture negative. Here, we examine
      anti-phospholipid IgM antibody level changes as a biomarker for treatment
      response in smear positive TB patients. Serum samples were obtained from 40
      pulmonary TB patients at the start and end of the intensive phase treatment (IPT)
      from the CDC-TB Trials Consortium randomized clinical trial in Kampala, Uganda.
      Samples were screened by ELISA for IgM levels against five phospholipids found in
      Mycobacterium tuberculosis and host cells. Lipid antigens included cardiolipin
      (CL), phosphatidyl inositol (PI), phosphatidyl ethanolamine (PE), phosphatidyl
      choline (PTC), and sphingolipid (SL). Levels of IgM against all phospholipids
      significantly decreased (p = 0.034, 0.001, 0.008 0.008, 0.040, respectively)
      following anti-TB drug treatment in patients without lung cavitary disease at
      baseline. The mean sensitivity of this test in these patients was 83% when the
      IgM response to a single lipid antigen was used; it was >90% when responses to 2
      or more lipids were assessed. In contrast, cavitary TB patients showed an overall
      IgM increase, with a significant rise against PE (p = 0.025). There was no
      significant difference in the change in antibody levels between patients who
      remained culture-positive and those who culture-converted after 40 doses of drug
      therapy. The measurement of IgM anti-phospholipid antibodies may be a useful
      biomarker to monitor treatment response in non-cavitary TB patients.

PMID- 22406156
TI  - [Prader-Willi and Angelman syndromes: 21 years of experience].
AB  - INTRODUCTION: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) were the
      first syndromes in humans that were known to originate from the phenomenon of the
      genomic imprinting. We review our experience of 21 years with PWS and AS that
      were confirmed with the genetically. RESULTS: Of the 13,875 patients recorded
      during the study period, 11 were diagnosed with PWS (18%), 7 males (63.6%) and 4
      females (36.4%), with a mean age of 9.06 years (+/- 6.92, range: 0.68-21.6). The
      time of the follow up of this group was 3.83 years (+/- 4.03, range: 0.49-15.3),
      and the age at diagnosis was 4.4 years (+/- 6.84, range: 0.03-19.38). Almost
      three quarters (72.7% of the PWS patients had a uniparental dysomy and 27.3% a
      paternal deletion. Six patients (8%) were diagnosed with AS, 4 females (66.6%)
      and 2 males (33.4%), with a mean age of 14.65 years (+/- 11.89, range: 1.3-30.7).
      The time of follow up was 6.76 years (+/- 5.89,range: 0.16-15), and the age at
      diagnosis was 8.84 years (+/- 9.11, range: 1.10-23). A maternal deletion was
      present in 83.3% of the AS patients and 16.7% had a maternal dysomy. DISCUSSION:
      As genetic advances are made these pathologies are confirmed before. Unlike the
      data in the literature, in our series most patients diagnosed with PWS (72'3%)
      had uniparental disomy. Recent studies correlation genotype with phenotype, in
      PWS is more serious if it occurs a deletion and in SA is milder in the case of
      uniparental disomy. CONCLUSIONS: Genetic studies must be performed in view of the
      established clinical symptoms: neonatal hypotonia of unknown cause in PWS and
      psychomotor deficits with autism features, particularly associated with epilepsy,
      must be evaluated in AS to prevent diagnostic uncertainties, unnecessary
      complementary examinations and to provide early genetic counselling.

PMID- 22406157
TI  - [Recommendations issued by the Spanish Society of Pediatric Infectious Diseases
      for the follow-up of the child exposed to the human immunodeficiency virus and to
      antiretroviral drugs during pregnancy and the neonatal period].
AB  - Human immunodeficiency virus vertical transmission in developed countries has
      dramatically decreased to less than 2% over the last 15 years due to the
      consecutive implementation of different prophylactic measures, including the use
      of antiretrovirals, elective cesarean section and refraining from breastfeeding.
      The follow-up of these otherwise healthy children is, by far, the most common
      situation related to HIV infection that general pediatricians currently face in
      routine clinical care in Spain. These recommendations issued by the Spanish
      Society of Pediatric Infectious Diseases attempt to summarize the main aspects of
      this follow-up, including birth management, type of feeding, neonatal
      antiretroviral prophylaxis, HIV infection diagnosis, common early comorbidities,
      short- and mid-term toxicities, vaccination and other prophylactic measures and
      long-term follow-up.

PMID- 22406159
TI  - [Do paediatricians perform lumbar puncture correctly? Review of recommendations
      and analysis the technique in Spain].
AB  - INTRODUCTION: Lumbar puncture (LP) is a commonly performed procedure in
      paediatrics. Performing this technique properly can avoid the most common
      associated complications. OBJECTIVE: To assess whether paediatricians and
      paediatric residents in Spain follow current recommendations for the LP
      technique. MATERIAL AND METHODS: A cross-sectional study was conducted by sending
      a questionnaire by mail through the Spanish Society of Paediatric Emergencies,
      collecting demographic information and responses to multiple choice questions
      about LP technique. RESULTS: A total of 206 questionnaires were analysed, of
      which 143 (69.5%) were answered by paediatricians, and 63 (30.5%) by paediatric
      residents. The majority (128; 62.1%) of physicians did not allow parents to be
      present during LP, 198 (96.1%) routinely use analgesia and sedation; 84 (42%)
      only used local anaesthesia. The majority of respondents used standard Quincke
      needles (126; 62.7%). The bevel was correctly positioned when puncturing the dura
      mater by 22 residents (36.1%) and 21 paediatricians (15.1%), a variation that was
      statistically significant (P=.001). For neonatal lumbar punctures, 63
      paediatricians (46%) and 19 paediatric residents used a butterfly needle which
      did not contain a stylet, and this difference was also statistically significant
      (P=.035). Of those surveyed, 190 (92.2%) re-inserted the stylet when re
      orientating the needle, and 186 (93%) re-oriented this when removing it. The
      recommendation of bed rest was made by 195 (94.7%) physicians. CONCLUSIONS: The
      majority of paediatricians orient the bevel wrongly when inserting the needle
      during LP, and still use "butterfly" needles in newborns, despite warnings to the
      contrary. Paediatric residents and less experienced paediatricians follow the
      recommendations more frequently.

PMID- 22406158
TI  - [Moderate cerebral hypothermia in hypoxic-ischaemic encephalopathy: Experience
      after one year].
AB  - INTRODUCTION: Moderate cerebral hypothermia has been shown to be an effective
      intervention in decreasing mortality and major disabilities in infants with
      moderate-severe hypoxic-ischaemic encephalopathy (HIE). OBJECTIVES: To describe
      our experience within the first year of implementation, and to evaluate the
      feasibility and safety of this intervention. METHODS: Retrospective study of 20
      patients with moderate-severe HIE treated with whole body hypothermia in the
      Agrupacion Sanitaria Hospital Sant Joan de Deu-Hospital Clinic, between January
      2009 and June 2010. RESULTS: During this period, 50 patients with perinatal HIE,
      26 of them moderate- severe, were admitted to our units. Twenty patients received
      hypothermia (13 with severe and 7 with moderate HIE). All of them had at least
      one risk factor for perinatal hypoxia-ischaemia, and clinical signs of HIE.
      Fifteen had clinical and/or EEG seizures. Core temperature was maintained at 33.5
      +/- 0.5 degrees C in 76.5% of determinations for infants cooled with a manual
      control device, and in 93.6% for those cooled with a servo-controlled device
      (P<.0001). Re-warming took a median time of 10.5 hours. No potentially severe
      complications related to hypothermia were observed. Seven patients (35%) died,
      all of them with severe HIE. CONCLUSIONS: There were no difficulties in any of
      the steps of this intervention, and no potentially severe complications related
      to it were recorded. Both manual and servo-control methods are equally effective
      on maintaining the target temperature, although temperature shows less
      variability using the servo-controlled equipment.

PMID- 22406160
TI  - [Fibroma due to irritation].

PMID- 22406161
TI  - [Assessment of primary care paediatricians performance in a paediatric trauma
      simulation].
AB  - INTRODUCTION: Training by means of advanced simulation can improve the
      paediatrician's abilities in the management of paediatric trauma patients, as
      well as decreasing errors and increasing patient safety. The initial management
      is an essential factor in the outcome of an injured child. MATERIAL AND METHODS:
      A trauma patient scenario was included in a national simulation training program.
      The performances of 156 paediatric primary care providers, divided into 39 teams,
      who participated in the courses carried out from May 2008 until February 2010
      were retrospectively analysed. The evaluation of the scenario was based both on
      the primary survey suggested by the Working Group on Trauma of the SECIP, and in
      the 8 main targets of a simulation evaluation tool from the Cincinnati Children's
      Hospital trauma care program. RESULTS: A pulse oximeter was placed, the
      intravenous/intraosseous access was indicated, the blood pressure was checked,
      and the oxygen was applied In 100% of the scenarios. An intravenous fluid bolus
      was indicated in 87% of the scenarios. The Glasgow scale was performed in 5.1%,
      and the appropriate warming measures in 25.6%. The bilateral cervical
      immobilisation was incorrect in 35% of the scenarios (89.7%). The primary survey
      (ABCDE) was checked correctly in only one scenario. With a top score of 16, based
      on Cincinnati Hospital, the teams mean score was 5.3 +/-1.8. CONCLUSIONS: Primary
      care paediatricians have problems applying the primary ABCDE trauma care sequence
      and the cervical spine precautions in a trauma simulation scenario. Educational
      programs for paediatricians must improve the practical check points of the
      initial approach to trauma management.

PMID- 22406162
TI  - Effect of mitral valve repair on mitral-aortic coupling: a real-time three
      dimensional transesophageal echocardiography study.
AB  - BACKGROUND: The aortic valve and the mitral valve (MV) are coupled via fibrous
      tissue. Simultaneous dynamic analysis of the two valves' annuli has demonstrated
      that they have synchronous and reciprocal behavior. Accordingly, the aims of this
      study were to characterize mitral-aortic coupling (MAC) in three-dimensional
      space before and after MV repair and to identify the untoward effects of
      annuloplasty rings on MAC compared with normal valvular function. METHODS: Real
      time three-dimensional transesophageal echocardiography was performed on 28
      consecutive patients with degenerative MV disease and severe mitral regurgitation
      before and after MV repair and in 25 age-matched control subjects. Custom
      software was used to semiautomatically identify the mitral and aortic annuli
      throughout the cardiac cycle and to measure parameters describing valvular
      dynamics. RESULTS: Patients with mitral regurgitation before MV repair were
      characterized by altered morphology and function of the MV but preserved MAC
      because of the maintained ability of the mitral annulus to change size and
      position. MV repair together with annuloplasty ring implantation forced the
      mitral annulus to be smaller and less pulsatile, with decreased displacement
      ability compared with normal mitral annuli. Because of this alteration in MAC,
      the "unaffected" aortic annulus became less pulsatile and less mobile.
      CONCLUSIONS: This study shows unwanted and unexpected changes in aortic annular
      function secondary to mitral valve repair with an annuloplasty ring due to
      altered MAC mechanisms. These changes may alter the dynamic mechanism of the
      aortic root that facilitates blood ejection, so MAC should be considered and
      evaluated from diagnosis to treatment in MV disease.

PMID- 22406163
TI  - Global left ventricular longitudinal systolic strain for early risk assessment in
      patients with acute myocardial infarction treated with primary percutaneous
      intervention.
AB  - BACKGROUND: Left ventricular systolic function is a key determinant of outcome
      after ST-segment elevation myocardial infarction (STEMI). The aim of this study
      was to study speckle-tracking global longitudinal strain (GLS) for early risk
      evaluation in STEMI and compare it with left ventricular ejection fraction
      (LVEF), wall motion score index (WMSI), and end-systolic volume index (ESVI).
      METHODS: Five-hundred seventy-six patients underwent echocardiography <=24 hours
      after primary percutaneous coronary intervention for STEMI. The end point was the
      composite of death, hospitalization with reinfarction, congestive heart failure,
      or stroke. Associations with outcome were assessed by multivariate Cox regression
      with adjustment for clinical parameters. Hazard ratios (HRs) for events within
      the first year are reported per absolute percentage GLS increase. RESULTS: During
      a median follow-up period of 24 months, 162 patients experienced at least one
      event. GLS was associated with the composite end point (adjusted HR, 1.20; 95%
      confidence interval [CI], 1.12-1.29) and also when controlling for LVEF (adjusted
      HR, 1.17; 95% CI, 1.07-1.29) and ESVI (adjusted HR, 1.18; 95% CI, 1.08-1.28).
      Although WMSI was significantly associated with outcome beyond any association
      accounted for by GLS, a borderline significant association was found after
      controlling for WMSI (adjusted HR for GLS, 1.10; 95% CI, 1.00-1.21). When GLS or
      WMSI was known, there was no significant association between LVEF or ESVI and
      outcome. CONCLUSIONS: In a large population of patients with STEMI, GLS and WMSI
      were comparable and both superior for early risk assessment compared with volume
      based left ventricular function indicators such as LVEF and ESVI. Compared with
      WMSI, the advantage of GLS is the provision of a semiautomated quantitative
      measure.

PMID- 22406164
TI  - Prevalence of non-cardiac pathology on clinical transthoracic echocardiography.
AB  - BACKGROUND: Non-cardiac findings (NCFs) are seen in more than a third of cardiac
      computed tomographic and cardiac magnetic resonance imaging studies. The
      prevalence and importance of NCFs in transthoracic echocardiographic (TTE)
      imaging is unknown. The aim of this study was to determine the prevalence of NCFs
      on TTE imaging. METHODS: The subcostal images of all comprehensive adult TTE
      studies performed at one institution in December 2008 were retrospectively
      reviewed for NCFs by a radiologist with fellowship training in cardiovascular and
      abdominal radiology and blinded to the TTE report findings and clinical
      histories. Additional TTE image orientations were assessed in a subset of 300
      studies. NCFs were categorized as benign (e.g., simple hepatic cyst),
      indeterminate (e.g., ascites), or worrisome (e.g., liver metastases). If an
      indeterminate or worrisome NCF was identified, the patient's electronic medical
      record was reviewed to determine if the NCF was previously known. RESULTS: Of
      1,008 TTE studies (443 inpatient, 565 outpatient) in 922 patients, 77 NCFs were
      identified in 69 patients (7.5%). These included 20 benign (26%), 52
      indeterminate (67%), and five worrisome (7%) NCFs. Intermediate and worrisome
      NCFs were more common in inpatient TTE studies (9% vs 3% outpatient, P = .002).
      The additional views demonstrated 2% more NCFs. Record review demonstrated that
      60% of worrisome and 67% of indeterminate NCFs were previously known. No unknown
      NCF ultimately led to a change in patient management. CONCLUSIONS: Clinical TTE
      studies demonstrate NCFs in 7.5% of all patients, with an increased prevalence on
      inpatient studies. Although 75% of NCFs were potentially management changing, the
      majority of these were previously known and very unlikely to lead to management
      changes. Further study is needed to validate these findings in other populations
      and to assess their clinical impact.

PMID- 22406165
TI  - Omega-3 biotechnology: Thraustochytrids as a novel source of omega-3 oils.
AB  - Thraustochytrids are large-celled marine heterokonts and classified as oleaginous
      microorganisms due to their production of docosahexaenoic (DHA) and
      eicosapentaenoic (EPA) omega-3-fatty acids. The applications of microbial DHA and
      EPA for human health are rapidly expanding, and a large number of clinical trials
      have been carried out to verify their efficacy. The development of refined
      isolation and identification techniques is important for the cultivation of
      thraustochytrids. With a high proportion of lipid biomass, thraustochytrids are
      also amenable to various production strategies which increase omega-3 oil output.
      Modifications to the existing lipid extraction methods and utilisation of
      sophisticated analytical instruments have increased extraction yields of DHA and
      EPA. Other metabolites such as enzymes, carotenoids and extracellular
      polysaccharides can also be obtained from these marine protists. Approaches such
      as the exploration for more diverse isolates having fast growth rates, metabolic
      engineering including gene cloning, and growing thraustochytrids on alternate low
      cost carbon source, will further enhance the biotechnological potential of
      thraustochytrids.

PMID- 22406166
TI  - Measurement of human latent Transforming Growth Factor-beta1 using a latency
      associated protein-reactive ELISA.
AB  - Human Transforming Growth Factor (TGF)-beta1, one of three TGF-beta isoforms, is
      a pleotropic cytokine critical for many physiological and immunological
      processes. TGF-beta1 is secreted in a latent form, linked to Latency Associated
      Protein (LAP). Analysis of Latent TGF-beta1 by TGF-beta1 ELISA requires
      dissociation of TGF-beta1 from LAP, e.g. by acidification of samples. The ELISA
      then measures total TGF-beta1, equivalent to dissociated Latent TGF-beta1 plus
      any free TGF-beta1 present prior to acidification. Evolutionary conservation of
      TGF-beta1 across mammals also renders TGF-beta1 ELISAs reactive with TGF-beta1 in
      bovine serum often used in human cell cultures. To enable a direct analysis of
      Latent TGF-beta1, monoclonal antibodies were made against LAP from human Latent
      TGF-beta1 and used to develop a LAP ELISA detecting Latent TGF-beta1. The ELISA
      did not react with LAP from human Latent TGF-beta2 or 3, respectively, nor with
      Latent TGF-beta in bovine serum. EDTA-containing plasma from healthy subjects
      (n=20) was analyzed by conventional TGF-beta1 ELISA and LAP ELISA. By TGF-beta1
      ELISA, total TGF-beta1 were detected in all samples (median 133 pM, range 34-348
      pM); low levels of free TGF-beta1 found in 8/20 non-acidified samples showed that
      >98.5% of the total TGF-beta1 derived from Latent TGF-beta1. Latent TGF-beta1
      found in non-acidified samples by LAP ELISA (median 154 pM, range 48-403 pM) was
      comparable in molar levels to, and correlated with, total TGF-beta1 (r(s) 0.96,
      p<0.0001). A similar agreement between the total TGF-beta1 and the LAP ELISA was
      found with citrate- and heparin-containing plasma. The LAP ELISA facilitates
      analysis of Latent TGF-beta1 without sample acidification and is not compromised
      by the presence of bovine serum in human cell supernatants.

PMID- 22406167
TI  - Biosynthesis of ethyl oleate, a primer pheromone, in the honey bee (Apis
      mellifera L.).
AB  - Honey bees undergo a physiological transition from nursing to foraging
      approximately 21 days after adult emergence. This transition is delayed by ethyl
      oleate (EO), a primer pheromone produced by foragers when exposed to ethanol from
      fermented nectar. We demonstrate here that two secreted alpha/beta-hydrolases
      (BeeBase ID: GB11403 and GB13365) are responsible for the reversible
      esterification of ethanol with oleic acid, giving EO. Expression of hydrolase
      GB11403 was shown to be significantly up-regulated in foragers, relative to
      nurses. Tissue perfusion experiments with labeled substrates consistently
      localized the highest level of EO production in the head, whereas in situ imaging
      revealed expression of relevant EO biosynthetic genes and enzymatic activity
      along the esophagus, the site of ethanol exposure during nectar intake. Both
      alpha/beta-hydrolases were expressed in Pichia pastoris, purified and were shown
      produce EO in vitro. Experiments with live bees fed ethanol demonstrated that EO
      formed in regurgitate accumulates in the honey crop and exudes to the
      exoskeleton, from where it exerts its primer effect on younger bees.

PMID- 22406168
TI  - Sildenafil, a phosphodiesterase type 5 inhibitor, enhances the activity of two
      atypical antidepressant drugs, mianserin and tianeptine, in the forced swim test
      in mice.
AB  - Sildenafil, a selective phosphodiesterase type 5 inhibitor, has recently been
      reported to abolish anti-immobility action of antidepressant drugs, i.e.,
      bupropion, venlafaxine and S-citalopram, in the forced swim test in mice. The
      present study was designed to investigate the influence of sildenafil on the
      potential of two atypical antidepressants, namely mianserin and tianeptine. Swim
      sessions were conducted by placing mice in glass cylinders filled with water for
      6 min and the duration of the behavioral immobility during the last 4 min of the
      test was evaluated. Locomotor activity was measured with photoresistor
      actimeters. To evaluate the potential pharmocokinetic interaction, total brain
      concentrations of the studied antidepressants were determined by HPLC method.
      Sildenafil at a dose of 2.5 mg/kg did not affect the activity of mianserin (20
      mg/kg) in the forced swim test. Interestingly, at higher doses (5 and 10 mg/kg),
      sildenafil significantly enhanced the anti-immobility action of mianserin.
      Likewise, sildenafil (5, 10 and 20 mg/kg) robustly augmented the antidepressant
      activity of tianeptine (30 mg/kg). Mianserin alone, as well as in a combination
      with sildenafil at the highest dose, caused a potent reduction in locomotor
      activity. However, the changes in motor activity did not interfere with the data
      obtained in the forced swim test. Sildenafil significantly increased the total
      brain tianeptine concentration. No alteration in mianserin level in the brain
      after sildenafil co-administration was observed. The present study suggests that
      sildenafil enhances the activity of mianserin and tianeptine in the forced swim
      test in mice. The changes in the antidepressant activity of mianserin evoked by
      sildenafil co-administration were related to pharmacodynamic interaction while
      the interaction between tianeptine and sildenafil was, at least in part,
      pharmacokinetic in nature.

PMID- 22406169
TI  - Complex phenotypes in mosquitoes and mice associated with neutralization escape
      of a Dengue virus type 1 monoclonal antibody.
AB  - DENV1-E106 is a monoclonal antibody (MAb) with strong neutralizing activity
      against all five DENV-1 genotypes and therapeutic activity in mice. Here, we
      evaluated the potential for DENV-1 to escape neutralization by DENV1-E106. A
      single mutation in domain III of the envelope protein (T329A) emerged, which
      conferred resistance to DENV1-E106. However, the T329A variant virus had
      differing phenotypes in vitro and in vivo with attenuation in cell culture yet
      increased infectivity in Aedes aegypti mosquitoes. Mice infected with this T329A
      variant still were protected against lethal infection by DENV1-E106 even though
      much of the neutralizing activity was lost. This study reveals the complex
      dynamics of neutralization escape of an inhibitory MAb against DENV, and suggests
      that evaluation of therapeutic MAbs requires detailed investigation in relevant
      hosts.

PMID- 22406170
TI  - Entire posterior process talus fracture: a report of two cases.
AB  - The complex anatomy of the posterior process of the talus includes the medial and
      lateral tubercles extending from the talar body. Review of the current literature
      indicates that fracture of the entire posterior process of the talus is a rare
      injury. Two patients presented to our emergency department after motor vehicle
      accidents, and both were diagnosed with entire posterior process talus fractures.
      After evaluation of each patient, treatment of each was undertaken by means of
      open reduction and internal fixation via the posteromedial approach to fracture.
      Headless screws were used to fixate the reduced posterior tubercle in each case.
      Based on our experience with the patients described in this report, open
      reduction and internal fixation appear to be suitable methods of treatment for
      complete posterior process fractures of the talus.

PMID- 22406171
TI  - Construction of a microbial natural product library for chemical biology studies.
AB  - The RIKEN Natural Products Depository (NPDepo) is a public depository of small
      molecules. Currently, the NPDepo chemical library contains 39,200 pure compounds,
      half of which are natural products and their derivatives. In order to reinforce
      the uniqueness of our chemical library, we have improved our strategies for the
      collection of microbial natural products. Firstly, a microbial metabolite
      fraction library coupled with an MP (microbial products) plot database provides a
      powerful resource for the efficient isolation of microbial metabolites. Secondly,
      biosynthetic studies of microbial metabolites have enabled us to not only access
      ingenious biosynthetic machineries, but also obtain a variety of biosynthetic
      intermediates. Our chemical library contributes to the discovery of molecular
      probes for increasing our understanding of complex biological processes and for
      eventually developing new drug leads.

PMID- 22406173
TI  - Methanogens: a window into ancient sulfur metabolism.
AB  - Methanogenesis is an ancient metabolism that originated on the early anoxic
      Earth. The buildup of O(2) about 2.4 billion years ago led to formation of a
      large oceanic sulfate pool, the onset of widespread sulfate reduction and the
      marginalization of methanogens to anoxic and sulfate-poor niches. Contemporary
      methanogens are restricted to anaerobic habitats and may have retained some
      metabolic relics that were common in early anaerobic life. Consistent with this
      hypothesis, methanogens do not utilize sulfate as a sulfur source, Cys is not
      utilized as a sulfur donor for Fe-S cluster and Met biosynthesis, and Cys
      biosynthesis uses an unusual tRNA-dependent pathway.

PMID- 22406172
TI  - Depth of treatment sensitive noise resistant dynamic artificial neural networks
      model of recall in people with prosopagnosia.
AB  - The Fusiform Face Area (FFA) is the brain region considered to be responsible for
      face recognition. Prosopagnosia is a brain disorder causing the inability to a
      recognise faces that is said to mainly affect the FFA. We put forward a model
      that simulates the capacity to retrieve label associated with faces and objects
      depending on the depth of treatment of the information. Akin to prosopagnosia,
      various localised "lesions" were inserted into the network in order to evaluate
      the degradation of performance. The network is first composed of a Feature
      Extracting Bidirectional Associative Memory (FEBAM-SOM) to represent the
      topological maps allowing the categorisation of all faces. The second component
      of the network is a Bidirectional Heteroassociative Memory (BHM) that links those
      representations to their semantic label. For the latter, specific semantic labels
      were used as well as more general ones. The inputs were images representing faces
      and various objects. Just like in the visual perceptual system, the images were
      pre-processed using a low-pass filter. Results showed that the network is able to
      associate the extracted map with the correct label information. The network is
      able to generalise and is robust to noise. Moreover, results showed that the
      recall performance of names associated with faces decrease with the size of
      lesion without affecting the performance of the objects. Finally, results
      obtained with the network are also consistent with human ones in that higher
      level, more general labels are more robust to lesion compared to low level,
      specific labels.

PMID- 22406174
TI  - Dense IgG4 plasma cell infiltrates associated with chronic infectious aortitis:
      implications for the diagnosis of IgG4-related disease.
AB  - BACKGROUND: IgG4-related aortitis is a newly recognized form of noninfectious
      aortitis that occurs as part of the spectrum of a systemic disease referred to as
      IgG4-related disease. IgG4-related aortitis is distinguished from giant cell
      aortitis and Takayasu aortitis in part by the presence of increased numbers of
      IgG4-expressing plasma cells. Chronic infectious aortitis can also display
      lymphoplasmacytic infiltrates, but the degree of IgG4 expression in these cases
      has not been specifically evaluated. METHODS: Two cases of chronic active
      infectious abdominal aortitis were prospectively identified. Both were due to
      gram-positive bacteria, and at least one of the cases was due to chronic active
      Staphylococcus aureus infection. The degree of IgG4 plasma cell infiltration was
      assessed by immunohistochemistry. RESULTS: Both cases of chronic infectious
      aortitis focally displayed high levels of IgG4-expressing plasma cells, greater
      than 50% of the IgG-expressing plasma cells, and greater than 50 IgG4-expressing
      plasma cells per high-power field. CONCLUSIONS: Focal dense IgG4 plasma cell
      infiltrates can be seen in association with chronic infectious aortitis due to
      gram-positive bacteria, including Staphylococcus aureus. This observation
      supports the proposal that chronic Staphylococcus aureus infection may stimulate
      a Th2-mediated elevation in IgG4. The pathologic diagnosis of IgG4-related
      aortitis should not be based solely on the presence of increased IgG4 plasma cell
      counts from immunohistochemistry, but requires consideration of the overall
      pathology, including careful exclusion of infectious aortitis.

PMID- 22406175
TI  - STAT6 and JAK1 are essential for IL-4-mediated suppression of prostaglandin
      production in human follicular dendritic cells: opposing roles of phosphorylated
      and unphosphorylated STAT6.
AB  - Prostaglandins (PGs) are emerging as important immune mediators. Since our first
      report on the expression of prostacyclin synthase in the germinal centers, we
      have investigated production mechanisms and biological functions of PG using
      human follicular dendritic cell (FDC)-like cells. In the previous report, we
      observed that TGF-beta enhances PG production, and IL-4 prevents this
      upregulation. To elucidate the inhibitory mechanism of IL-4, its effects on the
      key enzyme leading to PG production were analyzed in this study. IL-4 but not IL
      10 inhibited TGF-beta-induced COX-2 expression at both mRNA and protein levels.
      Next the early signaling molecules of IL-4 were identified by siRNA technology.
      IL-4 induced tyrosine phosphorylation of STAT1, 3, and 6, but only JAK1-STAT6
      pathway was responsible for the prevention of COX-2 augmentation and PG
      production. Phosphorylated STAT6 accumulated in the nucleus rapidly upon IL-4
      addition, and the complete inhibition of COX-2 upregulation required 24 h of
      pretreatment with IL-4, implying that newly transcribed molecules mediate the
      inhibitory signals downstream of STAT6. Interestingly, unphosphorylated STAT6
      proteins were constitutively expressed in the nucleus, and depletion of STAT6
      impaired background level expression of COX-2 and PGs. Our results highlight the
      crucial roles of TGF-beta and IL-4 in the regulation of PG production, which lead
      us to suggest that T cells play an important role in FDC production of PGs.

PMID- 22406176
TI  - Icaritin inhibits T cell activation and prolongs skin allograft survival in mice.
AB  - Icaritin is a native compound from Epimedium Genus, a traditional Chinese herbal
      medicine which is effective in treating asthma, autoimmune diseases and viral
      infections. In the present paper, the immunosuppressive effects of icaritin were
      found through in vitro and in vivo studies. Icaritin could dose-dependently
      inhibit murine CD4(+) T cells proliferation stimulated with mitogens or specific
      antigen ovabumin (OVA). Icaritin at 0.25-25MUM could down-regulate T cell
      activation marker CD25 expression and inhibit IL-2 production. It could also
      reduce the Th1 cytokine IFN-gamma production significantly if the T cells were
      activated by ConA or anti-CD3; while the inhibition of IL-4 secretion was only
      seen on anti-CD3 activated T cells treated with low concentrations of icaritin.
      In vivo study showed that treatment of icaritin at 10mg/kg/day on mice could
      suppress the immune response with prolonged allograft skin survival. Further
      study demonstrated that it reduced the alloantigen-induced splenocytes
      proliferation and Th1/Th2 cytokines. It could also increase NF-AT luciferase
      activity in Jurkat-NF-AT-luc T cells. The above results suggested that icaritin
      might be used to treat Th1 dominated immune diseases by interfering T cells
      activation with mechanism different to CsA.

PMID- 22406177
TI  - Contribution of brain dopamine, serotonin and opioid receptors in the mechanisms
      of neuroimmunomodulation: evidence from pharmacological analysis.
AB  - Neuromediators such as dopamine (DA), serotonin (5-HT) and neuroopioids are known
      to be involved in the immune response control. This review has summarized the
      evidence supporting roles for brain DA (D(1), D(2)), 5-HT (5-HT(1A), 5-HT(2A))
      and opioid (mu, delta, kappa) receptor subtypes in regulating immune function.
      Activation of postsynaptic D(1)- and D(2)-receptors produced immunostimulation
      while their blockade or activation of presynaptic D(2)-receptors mediated an
      immunoinhibitory effect. Activation of mu- and delta(1)-opioid receptors also
      increased the immune reaction intensity. Activation of postsynaptic 5-HT(1A)-, 5
      HT(2A)-receptors, delta(2)- and kappa-opioid receptors resulted in
      immunosuppression while the blockade of postsynaptic 5-HT(1A)-, 5-HT(2A)
      receptors or activation of somatodendritic 5-HT(1A)-autoreceptors resulted in the
      immune response stimulation. Immunomodulating effects of drugs acting at various
      mediator and opioid receptor subtypes depend on the initial psychoemotional state
      of animals (aggression, submission, depression). The presented data may have
      implications for the treatment of emotional stress and mental disorders
      associated with changes in activity of brain DA, 5-HT, opioid systems and their
      receptor function as well as immune reactivity.

PMID- 22406178
TI  - A novel and precise method for simultaneous measurement of serum HDL and LDL
      subfractions and lipoprotein (a) cholesterol by ultracentrifugation and high
      performance liquid chromatography.
AB  - BACKGROUND: We developed an ultracentrifugation and high-performance liquid
      chromatography (HPLC) method for simultaneous measurement of cholesterol in serum
      high density lipoprotein (HDL) and low density lipoprotein (LDL) subfractions and
      lipoprotein (a) [Lp(a)]. METHODS: Serum aliquots of 0.05 ml were centrifuged at
      background densities of 1.006, 1.044 kg/l, and in the presence of beta
      mercaptoethanol (ME) at background densities of 1.044, 1.063 and 1.125 kg/l for
      the separation of lipoprotein subfractions and Lp(a). Cholesterol levels in the
      ultracentrifugal bottom fractions were analyzed by HPLC. RESULTS: ME effectively
      dissociated Lp(a) into apolipoprotein (a) and Lp(a) remnant [Lp(a-)]. Lp(a-)
      showed a distinctive density distribution from that of the native Lp(a). Based on
      these data, a method was developed to separate lipoprotein into subfractions and
      Lp(a) by ultracentrifugation. The separated HDL and LDL subfractions were not
      contaminated with Lp(a). This method is highly precise with the total CVs for the
      measurement of HDL2-C, HDL3-C, LDLa-C, LDLb-C and Lp(a)-C 0.85%-2.66%, 0.87%
      3.21%, 0.86%-1.11%, 2.59%-6.35% and 4.42%-12.29%, respectively. CONCLUSION: A new
      method for the separation of HDL and LDL subfractions and Lp(a) and simultaneous
      measurement of cholesterol by ultracentrifugation and HPLC have been established.
      It is precise and sensitive and can be used in research or clinical laboratories
      for lipoprotein profiling.

PMID- 22406179
TI  - Red blood cell distribution width predicts early mortality in patients with acute
      dyspnea.
AB  - BACKGROUND: Red blood cell distribution width (RDW) has been shown to predict
      clinical outcomes in cardiovascular diseases. We studied whether RDW is useful to
      predict early mortality in patients with acute dyspnea at an emergency department
      (ED). METHODS: We retrospectively analyzed 907 patients with acute dyspnea who
      visited the ED from January 2009 to May 2009. Primary outcome was 30-day
      mortality. RESULTS: Acute decompensated heart failure (29.9%) was the most common
      adjudicated discharge diagnosis followed by cancer (14.8%) and pneumonia (12.5%).
      There was a stepwise increase of 30-day mortality risk from lowest (RDW<12.9%) to
      highest (RDW>14.3%) RDW tertiles (1.4% vs. 8.3% vs. 18.3%; log-rank P<0.001). In
      multivariate Cox hazard analysis, RDW was an independent predictor of 30-day
      mortality after adjusting for other risk factors (HR 1.23; 95% CI 1.11-1.36;
      P<0.001). Adding RDW to conventional clinical predictors significantly improved
      prediction for 30-day mortality as measured by the area under the ROC curve (AUC,
      from 0.873 to 0.885; P=0.023) and the net reclassification improvement
      (NRI=14.1%; P<0.001)/integrated discrimination improvement (IDI=0.038; P=0.006).
      CONCLUSIONS: Our findings suggest that RDW measured at ED is an independent and
      additive predictor of early mortality in patients with acute dyspnea.

PMID- 22406180
TI  - Association between HbA1c and dipeptidyl peptidase IV activity in type 2 diabetes
      mellitus.

PMID- 22406181
TI  - Synthetic calibrators for the analysis of total metanephrines in urine:
      revisiting the conditions of hydrolysis.
AB  - BACKGROUND: The quantification of total (free+sulfated) metanephrines in urine is
      recommended to diagnose pheochromocytoma. Urinary metanephrines include
      metanephrine itself, normetanephrine and methoxytyramine, mainly in the form of
      sulfate conjugates (60-80%). Their determination requires the hydrolysis of the
      sulfate ester moiety to allow electrochemical oxidation of the phenolic group.
      Commercially available urine calibrators and controls contain essentially free,
      unhydrolysable metanephrines which are not representative of native urines. The
      lack of appropriate calibrators may lead to uncertainty regarding the completion
      of the hydrolysis of sulfated metanephrines, resulting in incorrect
      quantification. METHODS: We used chemically synthesized sulfated metanephrines to
      establish whether the procedure most frequently recommended for commercial kits
      (pH 1.0 for 30 min over a boiling water bath) ensures their complete hydrolysis.
      RESULTS: We found that sulfated metanephrines differ in their optimum pH to
      obtain complete hydrolysis. Highest yields and minimal variance were established
      for incubation at pH 0.7-0.9 during 20 min. CONCLUSION: Urinary pH should be
      carefully controlled to ensure an efficient and reproducible hydrolysis of
      sulfated metanephrines. Synthetic sulfated metanephrines represent the optimal
      material for calibrators and proficiency testing to improve inter-laboratory
      accuracy.

PMID- 22406182
TI  - Alexithymia and anxiety sensitivity in populations at high risk for panic
      disorder.
AB  - OBJECTIVE: Populations at high risk for panic disorder (PD) probably share with
      subjects with PD an underlying vulnerability involving features like anxiety
      sensitivity (AS) and alexithymia. The present study would verify if PD relatives
      (R) and subjects who have experienced 1 or more panic attacks (PAs) show
      different levels of AS and alexithymia with respect to healthy controls (HC).
      METHODS: One hundred fifty-seven HCs, 30 subjects with PA, 64 R subjects, and 139
      outpatients with PD were evaluated and compared on AS, alexithymia, and control
      variables. RESULTS: Subjects with PD show higher alexithymia and AS levels
      compared with HCs; R subjects do not differ on ASI total score; and R females
      show more alexithymic features. Subjects with PA are comparable with HCs both on
      AS and alexithymia. CONCLUSIONS: Results confirm an impairment in emotional and
      bodily sensations information processing in subjects with PD but partially
      disconfirm the expectation of a difference between R subjects and subjects with
      PA with respect to HCs on AS and alexithymia. Emotional and bodily sensation
      competencies could be protective factors for PD in high-risk populations.

PMID- 22406183
TI  - Vertically aligned carbon nanofiber as nano-neuron interface for monitoring
      neural function.
AB  - Neural chips, which are capable of simultaneous multisite neural recording and
      stimulation, have been used to detect and modulate neural activity for almost
      thirty years. As neural interfaces, neural chips provide dynamic functional
      information for neural decoding and neural control. By improving sensitivity and
      spatial resolution, nano-scale electrodes may revolutionize neural detection and
      modulation at cellular and molecular levels as nano-neuron interfaces. We
      developed a carbon-nanofiber neural chip with lithographically defined arrays of
      vertically aligned carbon nanofiber electrodes and demonstrated its capability of
      both stimulating and monitoring electrophysiological signals from brain tissues
      in vitro and monitoring dynamic information of neuroplasticity. This novel nano
      neuron interface may potentially serve as a precise, informative, biocompatible,
      and dual-mode neural interface for monitoring of both neuroelectrical and
      neurochemical activity at the single-cell level and even inside the cell. FROM
      THE CLINICAL EDITOR: The authors demonstrate the utility of a neural chip with
      lithographically defined arrays of vertically aligned carbon nanofiber
      electrodes. The new device can be used to stimulate and/or monitor signals from
      brain tissue in vitro and for monitoring dynamic information of neuroplasticity
      both intracellularly and at the single cell level including neuroelectrical and
      neurochemical activities.

PMID- 22406184
TI  - Nitric oxide-releasing nanoparticles accelerate wound healing in NOD-SCID mice.
AB  - Wound healing is a complex process, coordinated by various biological factors. In
      immunocompromised states wound healing can be interrupted as a result of
      decreased numbers of immune cells, impairing the production of effector molecules
      such as nitric oxide (NO). Therefore, topical NO-releasing platforms, such as
      diethylenetriamine (DETA NONOate), have been investigated to enhance wound
      healing. Recently, we demonstrated a nanoparticle platform that releases NO (NO
      NPs) in a sustained manner, accelerating wound healing in both uninfected and
      infected murine wound models. Here, NO-NPs were investigated and compared to DETA
      NONOate in an immunocompromised wound model using non-obese, diabetic, severe
      combined immunodeficiency mice. NO-NP treatment accelerated wound closure as
      compared to controls and DETA NONOate treatment. In addition, histological
      assessment revealed that wounds treated with NO-NPs had less inflammation, more
      collagen deposition, and more blood vessel formation as compared to other groups,
      consistent with our previous data in immunocompetent animals. These data suggest
      that NO-NPs may serve as a novel wound-healing therapy in the setting of
      immunocompromised states associated with impaired wound healing. FROM THE
      CLINICAL EDITOR: Wound healing in an immunocompromised host is often incomplete
      and is a source of major concern in such conditions. This work demonstrates in a
      murine model that in these settings NO releasing nanoparticles significantly
      enhance wound healing.

PMID- 22406185
TI  - Acute vascular effects of nanoparticle infusion in isolated perfused skin.
AB  - The majority of studies on the effect of nanomaterials on biological function
      involves either isolated in vitro cell systems or are concerned with in vivo
      effects after inhalational or dermal exposure. The current work reports on an
      intriguing observation of the vascular effects seen in an ex vivo perfused tissue
      preparation, the isolated perfused porcine skin flap (IPPSF), in studies
      conducted to assess nanomaterial biodistribution. Compared with a relatively
      large dataset involving organic chemical infusions (n = 53), infusion of six
      different nanoparticles of diverse sizes and composition (silica or dextran
      coated Fe(2)O(3), silica or citrate coated silver, PEG or carboxylated quantum
      dots [QD]) resulted in statistically significant post-infusion flap weight gain
      and an increase in arterial perfusion pressure (especially with QD-PEG). In
      contrast, infusion with nC(60) nanoparticles did not produce these effects. These
      observations suggest certain nanoparticle infusions may be associated with acute
      vascular physiologic effects that merit further attention. FROM THE CLINICAL
      EDITOR: In this study utilizing a perfused porcine skin flap, specific
      nanoparticle infusions were demonstrated to be associated with significant acute
      vascular physiological effects.

PMID- 22406186
TI  - Tracking T-cells in vivo with a new nano-sized MRI contrast agent.
AB  - Non-invasive in vivo tracking of T-cells by magnetic resonance imaging (MRI) can
      lead to a better understanding of many pathophysiological situations, including
      AIDS, cancer, diabetes, graft rejection. However, an efficient MRI contrast agent
      and a reliable technique to track non-phagocytic T-cells are needed. We report a
      novel superparamagnetic nano-sized iron-oxide particle, IOPC-NH2 series
      particles, coated with polyethylene glycol (PEG), with high transverse relaxivity
      (250 s(-1) mM(-1)), thus useful for MRI studies. IOPC-NH2 particles are the first
      reported magnetic particles that can label rat and human T-cells with over 90%
      efficiency, without using transfection agents, HIV-1 transactivator peptide, or
      electroporation. IOPC-NH2 particles do not cause any measurable effects on T-cell
      properties. Infiltration of IOPC-NH2-labeled T-cells can be detected in a rat
      model of heart-lung transplantation by in vivo MRI. IOPC-NH2 is potentially
      valuable contrast agents for labeling a variety of cells for basic and clinical
      cellular MRI studies, e.g., cellular therapy. FROM THE CLINICAL EDITOR: In this
      study, a novel PEG coated superparamagnetic nano-sized iron-oxide particle was
      investigated as a T-cell labeling agent for MRI studies. The reported particles
      can label T-cells with over 90% efficiency, without using transfection agents,
      HIV-1 transactivator peptide, or electroporation, therefore may enable more
      convenient preclinical call labeling studies.

PMID- 22406188
TI  - Effects of nanoparticle surface-coupled peptides, functional endgroups, and
      charge on intracellular distribution and functionality of human primary
      reticuloendothelial cells.
AB  - The medical use of nanoparticles (NPs) has to consider their interactions with
      the cells of the reticuloendothelial system. In this study the authors used gold
      nanorods coated by PEG chains bearing peptides or charged functional groups to
      study their influence on the uptake, subcellular distribution, and activation of
      human primary reticuloendothelial cells: monocytes, macrophages (MPhi), immature
      and mature dendritic cells (DC), and endothelial cells (EC). We found that beside
      MPhi and immature DC also EC internalize large quantities of NPs and observed an
      increased uptake of positively charged particles. Most notably, NPs accumulated
      in the MHC II compartment in mature DC that is involved in antigen processing.
      Furthermore, surface-coupled peptide sequences RGD and GLF altered the activation
      profile of DC, and modulated cytokine release in both DC and MPhi in a cell
      specific manner. These data suggest that the charge of NPs mainly influences
      their uptake, whereas conjugated peptides alter cell functions. FROM THE CLINICAL
      EDITOR: In this paper the interactions between RES cells and nanoparticles is
      investigated, concluding that in the case of gold nanorods charge determines
      uptake characteristics, whereas conjugated peptides determine their function.

PMID- 22406189
TI  - A new nano-cryosurgical modality for tumor treatment using biodegradable MgO
      nanoparticles.
AB  - A new conceptual modality for nano-cryosurgical ablation of tumors is proposed in
      this article. The main strategy is to apply MgO nanoparticles (NPs), which are
      nontoxic, biodegradable, and have few side-effects on the human body, to mediate
      the freezing procedure effectively. Detailed investigation via animal experiments
      and nucleation analysis demonstrated that delivery of MgO NPs into the target
      tissues would significantly improve the cryosurgical outcome. The formation of an
      iceball during the freezing process is accelerated and enlarged due to the
      excellent thermal properties of MgO NPs. In addition this method could promote
      the generation of ice nuclei and thus enhance cryoinjury to the target cells.
      Therefore, combining the biodegradability and nontoxicity of MgO NPs with their
      relatively lightweight properties, excellent thermal properties would help
      develop a high-performance cryosurgery. These findings may lead to methods for
      safe and targeted nano-cryosurgery and possibly break through the barriers facing
      current clinical treatments of cancer. FROM THE CLINICAL EDITOR: Cryosurgery is a
      promising evolving modality to address malignancies. The work presented in this
      paper may add a novel concept to the field of nanomedicine by demonstrating that
      MgO nanoparticles enable more efficient ice-ball formation and cryoinjury in the
      target tissue.

PMID- 22406187
TI  - NTS-Polyplex: a potential nanocarrier for neurotrophic therapy of Parkinson's
      disease.
AB  - Nanomedicine has focused on targeted neurotrophic gene delivery to the brain as a
      strategy to stop and reverse neurodegeneration in Parkinson's disease. Because of
      improved transfection ability, synthetic nanocarriers have become candidates for
      neurotrophic therapy. Neurotensin (NTS)-polyplex is a "Trojan horse" synthetic
      nanocarrier system that enters dopaminergic neurons through NTS receptor
      internalization to deliver a genetic cargo. The success of preclinical studies
      with different neurotrophic genes supports the possibility of using NTS-polyplex
      in nanomedicine. In this review, we describe the mechanism of NTS-polyplex
      transfection. We discuss the concept that an effective neurotrophic therapy
      requires a simultaneous effect on the axon terminals and soma of the remaining
      dopaminergic neurons. We also discuss the future of this strategy for the
      treatment of Parkinson's disease. FROM THE CLINICAL EDITOR: This review paper
      focuses on nanomedicine-based treatment of Parkinson's disease, a
      neurodegenerative condition with existing symptomatic but no curative treatment.
      Neurotensin-polyplex is a synthetic nanocarrier system that enables delivery of
      genetic cargo to dopaminergic neurons via NTS receptor internalization.

PMID- 22406190
TI  - Protein- and peptide-based electrospun nanofibers in medical biomaterials.
AB  - Electrospun fibers are being studied and developed because they hold considerable
      promise for realizing some advantages of nanostructured materials. The fibers can
      be made of biocompatible and biodegradable polymers. Electrospinning has
      therefore attracted interest in biotechnology and medicine, and there has been
      rapid growth in this area in recent years. This review presents an introduction
      to polymer nanofiber electrospinning, focusing on the use of natural proteins and
      synthetic peptides. We summarize key physical properties of protein-based and
      peptide-based nanofiber mats, survey biomedical applications of these materials,
      identify key challenges, and outline future prospects for development of the
      technology for tissue engineering, drug delivery, wound healing, and biosensors.
      FROM THE CLINICAL EDITOR: This review focuses on polymer nanofiber
      electrospinning using natural proteins and synthetic peptides. The authors
      describe key properties and applications of these materials, and outline future
      prospects for tissue engineering, drug delivery, wound healing, and biosensors
      based on these nanomats and nanofibers.

PMID- 22406191
TI  - Phenotypic heterogeneity in a large Thai slow-channel congenital myasthenic
      syndrome kinship: Correction.

PMID- 22406193
TI  - Insurance and clinical trials.

PMID- 22406192
TI  - Tobacco dependence counseling in a randomized multisite clinical trial.
AB  - Pharmacotherapy trials for treating tobacco dependence would benefit from
      behavioral interventions providing treatment consistent with clinical practice
      guidelines but not directing participants to treatments not evaluated in the
      trial. The Smoke Free and Living It(c) behavioral intervention manual includes
      participant and interventionist guides and is designed to provide both practical
      counseling and intra-treatment support. We utilized this intervention manual in a
      multicenter, randomized clinical trial of smokers with attention deficit
      hyperactivity disorder. In this study, we evaluated how the interventional manual
      performed in a "train-the-trainer" model requiring uniform counseling across 6
      sites and 15 interventionists. We analyzed the skill-adherence of the
      interventionists and the intervention-adherence of the participants. The 255
      randomized participants completed 9.3+/-2.8 sessions (mean+/-SD), with 157
      participants (61.6%) completing all 11 of the sessions and 221 (86.7%) completing
      at least 6 of the 11 sessions. Of the 163 sessions for which the study
      interventionists were evaluated, 156 (95.7%) were rated as adherent to protocol
      and "meeting expectations" on at least 6 of 7 established criteria, illustrating
      that fidelity can be maintained with minimal supervision. The self-help and
      interventionists guides of the Smoke Free and Living It manual can thus be used
      to provide behavioral intervention with a high rate of adherence by both the
      interventionists and the participants. This manual meets the requirements of the
      United States Public Health Service Clinical Practice Guideline, can be adapted
      to specific research protocols, and provides a useful option for behavioral
      intervention during clinical trials for smoking cessation.

PMID- 22406194
TI  - Stochastic formulation of ecological models and their applications.
AB  - The increasing use of computer simulation by theoretical ecologists started a
      move away from models formulated at the population level towards individual-based
      models. However, many of the models studied at the individual level are not
      analysed mathematically and remain defined in terms of a computer algorithm. This
      is not surprising, given that they are intrinsically stochastic and require tools
      and techniques for their study that may be unfamiliar to ecologists. Here, we
      argue that the construction of ecological models at the individual level and
      their subsequent analysis is, in many cases, straightforward and leads to
      important insights. We discuss recent work that highlights the importance of
      stochastic effects for parameter ranges and systems where it was previously
      thought that such effects would be negligible.

PMID- 22406196
TI  - Introducing GRADE across the NICE clinical guideline program.
AB  - OBJECTIVES: Grading of Recommendations Assessment, Development and Evaluation
      (GRADE) is a system for rating the confidence in estimates of effect and grading
      guideline recommendations. It promotes evaluation of the quality of the evidence
      for each outcome and an assessment of balance between desirable and undesirable
      outcomes leading to a judgment about the strength of the recommendation. In 2007,
      the National Institute for Health and Clinical Excellence began introducing GRADE
      across its clinical guideline program to enable separation of judgments about the
      evidence quality from judgments about the strength of the recommendation. STUDY
      DESIGN AND SETTING: We describe the process of implementing GRADE across
      guidelines. RESULTS: Use of GRADE has been positively received by both technical
      staff and guideline development group members. CONCLUSION: A shift in thinking
      about confidence in the evidence was required leading to a more structured and
      transparent approach to decision making. Practical problems were also
      encountered; these have largely been resolved, but some areas require further
      work, including the application of imprecision and presenting results from
      analyses considering more than two alternative interventions. The use of GRADE
      for nonrandomized and diagnostic accuracy studies needs to be refined.

PMID- 22406195
TI  - Differential regulation of EHD3 in human and mammalian heart failure.
AB  - Electrical and structural remodeling during the progression of cardiovascular
      disease is associated with adverse outcomes subjecting affected patients to overt
      heart failure (HF) and/or sudden death. Dysfunction in integral membrane protein
      trafficking has long been linked with maladaptive electrical remodeling. However,
      little is known regarding the molecular identity or function of these
      intracellular targeting pathways in the heart. Eps15 homology domain-containing
      (EHD) gene products (EHD1-4) are polypeptides linked with endosomal trafficking,
      membrane protein recycling, and lipid homeostasis in a wide variety of cell
      types. EHD3 was recently established as a critical mediator of membrane protein
      trafficking in the heart. Here, we investigate the potential link between EHD3
      function and heart disease. Using four different HF models including ischemic rat
      heart, pressure overloaded mouse heart, chronic pacing-induced canine heart, and
      non-ischemic failing human myocardium we provide the first evidence that EHD3
      levels are consistently increased in HF. Notably, the expression of the Na/Ca
      exchanger (NCX1), targeted by EHD3 in heart is similarly elevated in HF. Finally,
      we identify a molecular pathway for EHD3 regulation in heart failure downstream
      of reactive oxygen species and angiotensin II signaling. Together, our new data
      identify EHD3 as a previously unrecognized component of the cardiac remodeling
      pathway.

PMID- 22406197
TI  - [A pre-auricular tumour].

PMID- 22406198
TI  - Proteomic analysis of plasma from a Tau transgenic mouse.
AB  - The neurofibrillary tangles (NFTs) formed by the accumulation of abnormal tau
      filaments have been shown to be involved in Alzheimer's disease (AD) brain
      degeneration. In this study, a tau transgenic mouse (pNSE/htau23) model was used
      to monitor changes in protein levels and to search for novel biomarker candidates
      suitable for the early diagnosis of AD before onset of clinical symptoms. Plasma
      samples from 2-month (n=13, asymptomatic) and 4-month (n=7, symptomatic) tau
      transgenic mice were compared to the control group (n=8) by 2-dimensional gel
      electrophoresis (2-DE) coupled with liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). Three proteins, ATP synthase, Adenosine kinase and
      Regucalcin showed significantly decreased levels in the plasma of tau transgenic
      mouse, which was further confirmed by Western blotting. This study suggests that
      these proteins could be used as candidate biomarkers for early diagnosis of AD in
      combination with previously discovered protein biomarkers.

PMID- 22406199
TI  - Origin of climbing fiber neurons and the definition of rhombic lip.
AB  - Wilhelm His identified the rhombic lip in human embryos a century ago and thought
      that all mossy and climbing fiber neurons are derived from it. This has been
      accepted for more than one hundred years. However, recent genetic fate mapping
      studies have demonstrated that mossy fiber and climbing fiber neurons have
      distinct progenitor pools and originate from different subdomains in the
      ventricular zone of the caudal hindbrain. The majority of climbing fiber neurons
      has been found to derive from more medial parts of the caudal hindbrain although
      its dorsal boundary is unclear currently. Subsequently, several new definitions
      for the rhombic lip have been made according to the expression domain of
      different transcription factors, such as Math1, Wnt1 and Olig3, which have
      different ventral boundaries and make the area of rhombic lip confused.
      Therefore, a precise definition for rhombic lip is still lacking for the main
      reason that the origin of the entire inferior olivary nuclei is still unclear.
      Further genetic fate mapping is needed to determine the origin of all climbing
      fiber neurons which will help to give the rhombic lip an unambiguous definition.

PMID- 22406200
TI  - Exploring the link between self-compassion and body image in university women.
AB  - The purpose of the present research was to examine the relationships between self
      compassion and women's body image. In Study 1, female undergraduates (N=142)
      completed three measures of body image and measures of self-esteem and self
      compassion. Results showed that high self-compassion predicted fewer body
      concerns independently of self-esteem. Moreover, when both self-compassion and
      self-esteem were included as predictors, self-compassion accounted for unique
      variance in body preoccupation and weight concerns whereas self-esteem did not.
      In Study 2, this finding was partially replicated with one component (self
      judgment) of self-compassion uniquely predicting body preoccupation in
      undergraduate women (N=187). High scores on self-compassion also predicted less
      eating guilt independent of self-esteem. Additionally, self-compassion was shown
      to partially mediate the relationship between body preoccupation and depressive
      symptoms. The findings highlight the possibility that a consideration of self
      compassion for body image may contribute to identifying who is most at risk for
      body/shape concerns.

PMID- 22406201
TI  - Effects of anthropogenic inputs on the organic quality of urbanized streams.
AB  - Due to arid conditions, population growth, and anthropogenic impacts from
      agricultural and urban development, wastewater effluent makes up an increasingly
      large percentage of surface water supplies promoting concerns about the potential
      ecological and human health effects associated with the organic quality of
      surface waters receiving treated wastewater discharge. Anthropogenic inputs alter
      the quality and quantity of organic carbon and also affect the ability of aquatic
      ecosystems to retain or transform carbon and other nutrients. In this paper, we
      use pyrolysis-GC/MS (Py-GC/MS) as a tool to examine whether the dissolved organic
      carbon (DOC) in suburban streams influenced by anthropogenic inputs displays an
      organic signature that is structurally different from natural organic material
      (NOM). Py-GC/MS was not only able to differentiate among stream sites that
      received discharge from upstream wastewater treatment plants and those that did
      not, but also distinguished stream sites influenced significantly by storm water.
      Distinct organic signatures were evident in stream waters with upstream
      wastewater treatment plant discharges regardless of the distance from effluent
      discharge, indicative of the persistent nature of effluent-derived organic
      material (EfOM). The pyrolysis fragments of 3-methyl-pyridine, 2-methyl-pyridine,
      pyrrole, and acetamide were identified as indicators of EfOM, supporting previous
      research that has suggested that protein and aminosugar derivitives are possible
      wastewater markers. Furthermore, pyrolysis fragments associated with soil
      polycarboxylic acids correlated highly with stream sites having the least
      anthropogenic influences.

PMID- 22406202
TI  - Profiling bulking and foaming bacteria in activated sludge by high throughput
      sequencing.
AB  - Bulking and foaming bacteria (BFB) are notorious in wastewater treatment although
      they are always presented in the normal activated sludge and playing certain
      roles other than being harmful. Previous studies using microscopy or conventional
      molecular methods could hardly get the full profile of the BFB in the normal
      activated sludge. In this study, high throughput sequencing was adopted to
      investigate the BFB community, which was sub-dominant in activated sludge from 14
      global wastewater treatment plants. The full-length 16S rRNA gene sequences of
      BFB groups were collected from previous studies to build a database for local
      BLAST and subsequent taxonomic assignment. The total BFB percentage in each
      sample ranged from 1.86% to 8.99% according to the 16S rRNA gene V4 pyrotags
      detected at the BLAST similarity cutoff of 97%. The most abundant and frequent
      BFB groups are 'Nostocoida limicola' I and II, Mycobacterium fortuitum, Type
      1863, and 'Microthrix parvicella'. The BFB among the activated sludge samples
      were both biogeographically and technological distributed to some extent. An
      extending application was performed to evaluate and design oligonucleotides
      probes based on the rich information of high similar sequences. Our study also
      gave an exemplified case of investigation on the specific sub-dominant functional
      groups in complex bacterial communities revealed by high throughput sequencing.

PMID- 22406203
TI  - Protective effect of yacon leaves decoction against early nephropathy in
      experimental diabetic rats.
AB  - Nephropathy is the most common cause of morbidity and mortality in diabetic
      patients. Prevention of this complication has a major relevance. Smallanthus
      sonchifolius (yacon) leaves have been shown to ameliorate hyperglycemia in
      streptozotocin-induced diabetic rats. We examined the beneficial effects of yacon
      leaves decoction on diabetic nephropathy and explored the possible underlying
      action mechanism. Streptozotocin-diabetic rats were orally administered 10% yacon
      leaves water decoction (70mg dry extract/kg body weight) once a day for 4weeks.
      Biochemical parameters in blood and urine were analyzed and immunohistochemistry
      staining, western immunoblotting and qRT-PCR were assessed. Yacon decoction
      significantly decreased high blood glucose level in diabetic rats and improved
      insulin production. Diabetic-dependent alterations in urinary albumin excretion,
      creatinine clearance, kidney hypertrophy and basement membrane thickening were
      attenuated by yacon decoction. These findings were associated with a marked
      decrease in TGF-beta1/Smad2/3 signaling. The expression of molecular markers of
      diabetic nephropathy such as collagen IV, laminin-1, fibronectin and collagen III
      were also diminished in the yacon-treated group compared to control diabetic
      group. These results suggest that yacon leaves decoction is a protective agent
      against renal damage in diabetic nephropathy, whose action can be mediated by TGF
      beta/Smads signals.

PMID- 22406204
TI  - Safety assessment of a new multivitamin.
AB  - A newly created multivitamin possesses many protective health functions. To
      investigate its safety when applied in medical treatment and when used as a food
      supplement, we studied its acute oral toxicity and 13-week oral toxicity in mice.
      The results showed that the oral lethal dose, 50% (LD(50)) of the biomass of the
      multivitamin in mice was greater than 2492 mg/kg body weight (BW) and that
      poisoned mice recovered within 72 h. The no observed effect level (NOEL) of long
      term consumption was more than 249.3mg/kg BW for haematological parameters,
      clinical chemistry parameters, histopathological examination of organs, food
      consumption, BW, ratio of organ weight to BW and other physiological parameters
      and conditions. Therefore, we conclude that dosages of up to 249.3 mg/kg BW/day
      of this multivitamin do not cause chronic toxicity in animals. Administration of
      this multivitamin may even improve the resistance of animals to negative
      environmental factors and may be safe for long-term consumption to enhance the
      health of individuals in accordance with the prescribed dosage (1.4 ~ 4.2 mg/kg
      BW/day).

PMID- 22406205
TI  - Fragrance material review on benzyl isobutyrate.
AB  - A toxicologic and dermatologic review of benzyl isobutyrate when used as a
      fragrance ingredient is presented. Benzyl isobutyrate is a member of the
      fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The
      AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with
      a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for benzyl isobutyrate were evaluated, then
      summarized, and includes: physical properties, acute toxicity, skin irritation,
      or skin sensitization data. A safety assessment of the entire AAASAE will be
      published simultaneously with this document. Please refer to Belsito et al.
      (2012) for an overall assessment of the safe use of this material and all AAASAE
      in fragrances.

PMID- 22406207
TI  - Chemical reduction of the mycotoxin beauvericin using allyl isothiocyanate.
AB  - Beauvericin (BEA) is a bioactive compound produced by the secondary metabolism of
      several Fusarium strains and known to have various biological activities. This
      study investigated the reduction of BEA present in the concentration of 25mg/kg
      on a solution model (phosphate buffer saline at pH 4 and 7) and in wheat flour
      using allyl isothiocyanate (AITC) as a reactant. The concentration of the
      mycotoxin studied was evaluated using liquid chromatography coupled to the diode
      array detector (LC-DAD), whereas adducts formed between the BEA and AITC were
      examined by liquid chromatography coupled to mass spectrometry-linear ion trap
      (LC-MS-LIT). In solution, BEA reduction ranged from 20% to 100% on a time
      dependent fashion and no significant differences were evidenced between the two
      pH levels employed. In the food system composed by wheat flour treated with
      gaseous AITC (50, 100 and 500 MUL/L), the BEA reduction varied from 10% to 65%
      and was dose-dependent. Two reaction products between the bioactive compounds
      employed in this study were identified, corresponding to BEA conjugates
      containing one or two AITC molecules.

PMID- 22406206
TI  - A 90-day oral (dietary) toxicity study of arruva, an R, R-monatin salt isomer, in
      Crl:CD-1(ICR) mice.
AB  - R,R-Monatin [2R,4R- isomer of 2-hydroxy-2-(indol-3-ylmethyl)-4-aminoglutaric
      acid] is one of four natural constituent isomers in the root bark of Sclerochitin
      ilicifolius; and "arruva" is the common/usual name that is proposed to represent
      R,R-monatin salt forms, which have potential use as high potency sweetener food
      ingredients. In the present study, groups of male and female Crl:CD-1(ICR) mice
      were exposed to 0 (control), 5000, 10,000, 20,000, or 35,000ppm of arruva in the
      diet for 90days. There were no toxicologically relevant clinical or
      histopathological findings in any of the test article-treated groups.
      Significantly lower mean body weights and cumulative body weight gains were noted
      in the 35,000ppm group when compared to the control group. Mean body weights in
      the 35,000ppm group males and females were 9% and 7% less than the control group,
      respectively, at week 13. In the absence of observations associated with systemic
      toxicity and in consideration of the magnitude of body weight difference, these
      effects were not considered toxicologically significant. Based on the results of
      this study, the dietary no-observed-adverse-effect level (NOAEL) of arruva for
      90days in male and female mice was 35,000ppm (equivalent to an exposure level of
      5764 and 8013mg/kg bw/day, respectively).

PMID- 22406208
TI  - Yersinia--flea interactions and the evolution of the arthropod-borne transmission
      route of plague.
AB  - Yersinia pestis, the causative agent of plague, is unique among the enteric group
      of Gram-negative bacteria in relying on a blood-feeding insect for transmission.
      The Yersinia-flea interactions that enable plague transmission cycles have had
      profound historical consequences as manifested by human plague pandemics. The
      arthropod-borne transmission route was a radical ecologic change from the food
      borne and water-borne transmission route of Yersinia pseudotuberculosis, from
      which Y. pestis diverged only within the last 20000 years. Thus, the interactions
      of Y. pestis with its flea vector that lead to colonization and successful
      transmission are the result of a recent evolutionary adaptation that required
      relatively few genetic changes. These changes from the Y. pseudotuberculosis
      progenitor included loss of insecticidal activity, increased resistance to
      antibacterial factors in the flea midgut, and extending Yersinia biofilm-forming
      ability to the flea host environment.

PMID- 22406210
TI  - Special issue on molecular evolution, epidemiology and pathogenesis of
      Mycobacterium tuberculosis and other mycobacteria.

PMID- 22406209
TI  - Abnormal anterior cingulate cortex activity predicts functional disability in
      schizophrenia.

PMID- 22406211
TI  - Reduction of chronic graft injury with a new HTK-based preservation solution in a
      murine heart transplantation model.
AB  - OBJECTIVE: Aim of this study was to evaluate a new histidine-tryptophan
      ketoglutarate (HTK)-based preservation solution on chronic isograft injury in
      comparison to traditional HTK solution. METHODS: Hearts of C57BL/6J (H-2b) mice
      were stored for 15 h in 0-4  degrees C cold preservation solution and then
      transplanted heterotopically into C57BL/6J (H-2b) mice. Three groups were
      evaluated: HTK, the base solution of a new preservation solution and hearts
      without cold ischemia (control). Time to restoration of heartbeat was measured
      (re-beating time). Strength of the heartbeat was palpated daily and scored on a 4
      level scale (palpation score). Animals were sacrificed after 60 days of
      observation (24 h for TGF-beta expression). The transplanted hearts were
      evaluated histologically for myocardial damage, vasculopathy and interstitial
      fibrosis. TGF-beta expression was assessed immunohistologically. All
      investigators were blinded to the groups. ANOVA and LSD post hoc test were used
      for statistical analysis. RESULTS: The re-beating time was significantly shorter
      in hearts stored in the new solution (10.3+/-2.6 min vs. HTK 14.2+/-4.1 min;
      p<0.05). The palpation score was significantly higher in hearts stored in the new
      solution (2.3+/-0.4 vs. HTK 1.6+/-0.5; p<0.01). Hearts stored in the new solution
      showed a lower myocardial injury score (1.8+/-0.2 vs. HTK 2.2+/-0.7), less
      interstitial fibrosis (4.8+/-1.9% vs. HTK 8.5+/-3.8%, p<0.05), less vasculopathy
      (14.7+/-6.9% vs. 22.0+/-23.2%; p=0.06) and lower TGF-beta1-expression (6.6+/-1.4%
      vs. HTK 12.0+/-4.6%). CONCLUSION: The new HTK-based solution reduces the chronic
      isograft injury. This protective effect is likely achieved through several
      modifications and supplements into the new solution like N-acetyl-L-histidine,
      glycine, alanine, arginine and sucrose.

PMID- 22406212
TI  - Freezing activities of flavonoids in solutions containing different ice
      nucleators.
AB  - In this study, we examined the effects on freezing of 26 kinds of flavonoid
      compounds, which were randomly selected as compounds with structures similar to
      those of flavonoid compounds existing in deep supercooling xylem parenchyma cells
      (XPCs) in trees, in solutions containing different kinds of ice nucleators,
      including the ice nucleation bacterium (INB) Erwinia ananas, INB Xanthomonas
      campestris, silver iodide, phloroglucinol and unidentified airborne impurities in
      buffered Milli-Q water (BMQW). Cumulative freezing spectra were obtained in each
      solution by cooling 2 MUL droplets at 0.2  degrees C/min by a droplet freezing
      assay. Freezing temperature of 50% droplets (FT(50)) was obtained from each
      spectra in a separate analysis with more than 20 droplets and mean FT(50) were
      obtained from more than five separate analyses using more than 100 droplets in
      total in each flavonoid. Supercooling-promoting activities (SCA) or ice
      nucleation-enhancing activities (INA) of these flavonoids were determined by the
      difference in FT(50) between control solutions without flavonoids and
      experimental solutions with flavonoids. In mean values, most of the compounds
      examined exhibited SCA in solutions containing the INB E. ananas, INB X.
      campestris, silver iodide, and phloroglucinol although the magnitudes of their
      activities were different depending on the ice nucleator. In solutions containing
      the INB E. ananas, 10 compounds exhibited SCAs with significant differences
      (p<0.05) in the range of 1.4-4.2  degrees C. In solutions containing silver
      iodide, 23 compounds exhibited SCAs with significant differences in the range of
      2.0-7.1  degrees C. In solutions containing phloroglucinol, six compounds
      exhibited SCAs with significant differences in the range of 2.4-3.5  degrees C.
      In solutions containing the INB X. campestris, only three compounds exhibited
      SCAs with significant differences in the range of 0.9-2.3  degrees C. In
      solutions containing unidentified airborne impurities (BMQW alone), on the other
      hand, many compounds exhibited INA rather than SCA. In mean values, only four
      compounds exhibited SCAs in the range of 2.4-3.2  degrees C (no compounds with
      significant difference at p<0.05), whereas 21 compounds exhibited INAs in the
      range of 0.1-12.3  degrees C (eight compounds with significant difference). It
      was also shown by an emulsion freezing assay that most flavonoid glycosides
      examined did not affect homogeneous ice nucleation temperatures, except for a few
      compounds that become ice nucleators in BMQW alone. These results suggest that
      most flavonoid compounds affect freezing temperatures by interaction with
      unidentified ice nucleators in BMQW as examined by a droplet freezing assay. The
      results of our previous and present studies indicate that flavonoid compounds
      have very complex effects to regulate freezing of water.

PMID- 22406213
TI  - The template technique for breast mound planning when using abdominal flaps for
      breast reconstruction.
AB  - Delayed breast reconstruction with abdominal flaps typically involves a process
      of 'trial and error' when moulding the flap into a satisfactory breast mound.
      This moulding process is crucial to the final aesthetic result. We present a
      template technique to preoperatively plan the skin envelope of each
      reconstruction. Templates are quick and simple to construct, and are tailor-made
      based on several measurements from the contralateral breast. The technique is
      versatile and can be adjusted for use with Wise-pattern breast reduction or
      mastopexy. In our experience, the template technique reliably attains natural
      shape and good symmetry when compared with unplanned flap moulding.

PMID- 22406214
TI  - Inter- and intra-tumoral heterogeneity in DNA damage evaluated by comet assay in
      early breast cancer patients.
AB  - There are no clinical tools to functionally assess degree of DNA damage in breast
      cancer. The comet assay is an accepted research tool for assessing DNA damage,
      however, most cancer studies have assessed lymphocytes as surrogate cells. The
      aim of this pilot study was to use the comet assay in early breast cancer
      directly in tumor tissue to compare DNA damage between and within traditionally
      defined subgroups, and to explore intra-tumoral heterogeneity. Scrapings of tumor
      and healthy breast tissue were obtained at primary surgery from 104 women. Comet
      assay was applied to quantitatively assess DNA damage, revealing substantial
      inter- and intra-subgroup variation. Marked intra-tumoral heterogeneity was
      evident across all subgroups. The degree of DNA damage for an individual could
      not be predicted by breast cancer subgroup. Comet assay warrants further study as
      a potential clinical tool for identification of tumoral DNA damage and
      ultimately, individualised use of DNA damaging therapy.

PMID- 22406216
TI  - The performance evaluation of a movable gamma-ray counting system for radwaste
      measurement.
AB  - Performance tests of a movable gamma-ray waste drum scanning system were carried
      out in this study. The scanner consists of a single HPGe detector on a movable
      cart with a 90 degrees  collimation angle to the observed item. The detection
      efficiency for (137)Cs was determined using the ISOTOPIC software. The activities
      of 35 low-level radioactive waste drums were measured using this system and
      compared with the results of two other measurement systems. This movable scanning
      system gave the same result as the other two systems with a relative spread (one
      standard deviation) of about 7.2%.

PMID- 22406215
TI  - Activation of p53/ATM-dependent DNA damage signaling pathway by shiga toxin in
      mammalian cells.
AB  - In this report, we studied the role of DNA damage signaling pathway in shiga
      toxin (STX)-induced mammalian cell death. Shiga toxin 1 exhibited cytotoxic
      activity in different mammalian cells such as HeLa cells, mouse embryo
      fibroblasts, and Caco-2 cells (a human intestinal primary fibroblast cell line).
      STX-1 was found to induce the release of cytochrome c from the mitochondria,
      nuclear condensation, and fragmentation of chromosomal DNA. STX-1 activated DNA
      damage signaling as determined by induction of H2AX phosphorylation and cleavage
      of PARP. Inhibition of caspase-3 reduced STX-1-induced phosphorylation of H2AX
      and nuclear condensation. It was also found that STX-1-induced p53 expression,
      and activated ATM in mammalian cells. STX-1-induced nuclear condensation
      significantly reduced in p53-, and ATM-knockout cells suggesting an involvement
      of p53 and ATM in transducing signals produced by STX in inducing apoptosis in
      mammalian cells. This is the first demonstration of involvement of ATM/p53 in STX
      inducing mammalian cell death.

PMID- 22406217
TI  - Distribution of 60Co in steel samples from Hiroshima.
AB  - This paper describes ultra low-level gamma-ray spectrometry measurements of the
      (60)Co activity distribution inside one 52 mm and one 41 mm thick steel sample.
      The samples had been exposed to the Hiroshima atomic bomb and were from the Aioi
      bridge and the Yokogawa bridge. Both samples were measured in a recent study
      aiming to back up model calculation of Hiroshima dosimetry. The (60)Co activity
      distributions found in this study support the assumptions made in the previous
      study.

PMID- 22406218
TI  - Prompt gamma neutron activation analysis of toxic elements in radioactive waste
      packages.
AB  - The French Alternative Energies and Atomic Energy Commission (CEA) and National
      Radioactive Waste Management Agency (ANDRA) are conducting an R&D program to
      improve the characterization of long-lived and medium activity (LL-MA)
      radioactive waste packages. In particular, the amount of toxic elements present
      in radioactive waste packages must be assessed before they can be accepted in
      repository facilities in order to avoid pollution of underground water reserves.
      To this aim, the Nuclear Measurement Laboratory of CEA-Cadarache has started to
      study the performances of Prompt Gamma Neutron Activation Analysis (PGNAA) for
      elements showing large capture cross sections such as mercury, cadmium, boron,
      and chromium. This paper reports a comparison between Monte Carlo calculations
      performed with the MCNPX computer code using the ENDF/B-VII.0 library and
      experimental gamma rays measured in the REGAIN PGNAA cell with small samples of
      nickel, lead, cadmium, arsenic, antimony, chromium, magnesium, zinc, boron, and
      lithium to verify the validity of a numerical model and gamma-ray production
      data. The measurement of a ~20kg test sample of concrete containing toxic
      elements has also been performed, in collaboration with Forschungszentrum Julich,
      to validate the model in view of future performance studies for dense and large
      LL-MA waste packages.

PMID- 22406219
TI  - Measurements of relative photon emission intensities and nuclear decay data
      evaluation of 113Sn.
AB  - In the frame of a co-operation between CEA-LIST/LNE-LNHB (France) and IFIN-HH
      (Romania), the relative intensities of the photon emissions following the (113)Sn
      decay were accurately determined at the LNHB using high resolution X- and gamma
      ray spectrometers, characterized by excellent quality efficiency calibrations.
      Two series of measurements were carried out. The intensity of the 255 keV gamma
      ray relative to that of the 392 keV gamma-ray was determined with an uncertainty
      lower than 1%. A new (113)Sn nuclear decay data evaluation was accomplished. The
      main results obtained are presented.

PMID- 22406220
TI  - Semi-automatic version of the potentiometric titration method for
      characterization of uranium compounds.
AB  - The potentiometric titration method was used for characterization of uranium
      compounds to be applied in intercomparison programs. The method is applied with
      traceability assured using a potassium dichromate primary standard. A semi
      automatic version was developed to reduce the analysis time and the operator
      variation. The standard uncertainty in determining the total concentration of
      uranium was around 0.01%, which is suitable for uranium characterization and
      compatible with those obtained by manual techniques.

PMID- 22406221
TI  - 57Co half-life determination.
AB  - The National Laboratory for Metrology of Ionizing Radiation (LNMRI)/Brazil
      participated in the last (57)Co activity measurement comparison organized by
      IAEA, in 2008. This was made in order to realize primary standardization of this
      radionuclide and to reduce the measuring uncertainties in the laboratory.
      Additionally, one sample with 2.6g was taken from the IAEA master solution of
      (57)Co and was prepared to be used in the measurement of the radionuclide's half
      life in an ionization chamber system. The (57)Co half-life was measured to be
      271.82 (17) days.

PMID- 22406222
TI  - Standardization, decay data measurements and evaluation of 64Cu.
AB  - The purposes of this study were to create national activity standards of (64)Cu,
      to make possible the definition of an international key comparison reference
      value and to determine the decay data in order to improve the decay scheme. Four
      laboratories measured the activity of a (64)Cu solution; these results were
      compared through the International Reference System. Moreover, the laboratories
      carried out new measurements of the photon emission intensities and of the half
      life. A new decay scheme was derived from these new values and the previously
      published ones.

PMID- 22406223
TI  - On within sample homogeneity testing using gamma-ray spectrometry.
AB  - Several problems concerning (133)Ba activity distribution in a cylindrical source
      were addressed by measurements with a 47% n-type HPGe detector and by simulation.
      Within-sample homogeneity was tested using the count rates from normal and from
      pure sum peaks. The sensitivity of front versus back source measurements to
      deviations from uniform distribution was studied. In the case of distributions
      symmetric with respect to the median plane of the source quantities that can
      provide information on the distribution of the activity were proposed.

PMID- 22406224
TI  - Abnormal collagen V deposition in dermis correlates with skin thickening and
      disease activity in systemic sclerosis.
AB  - OBJECTIVE: The physiological and mechanical properties of the skin, the primary
      tissue affected by systemic sclerosis, depend on the assembly of collagen types
      I, III and V, which form heterotypic fibers. Collagen V (COLV) regulates
      heterotypic fiber diameter, and the maintenance of its properties is important
      for maintaining normal tissue architecture and function. Based on a COLV-induced
      experimental SSc model, in which overexpression of abnormal COLV was a prominent
      feature, we assumed that this abnormality could be present in SSc patients and
      could be correlated to disease duration, skin thickening and disease activity.
      METHODS: Skin biopsies from 18 patients (6 early-stage and 12 late-stage) and 10
      healthy controls were studied. Skin thickening assessment was performed with the
      Modified Rodnan Skin Score (MRSS), and activity was calculated using the
      Valentini Disease Activity Index. Morphology, morphometry of COLV deposition in
      dermis, as well as, quantitative RT-PCR and 3D-reconstruction of the dermal
      fibroblast culture were performed. RESULTS: Structurally abnormal COLV was
      overexpressed in SSc skin, mainly in the early stages of the disease, when
      compared to normal controls and late-stage. A positive correlation between COLV
      expression and MRSS and disease activity was observed. Collagen V alpha-1 and
      alpha-2 mRNA expression levels were higher in SSc. Tridimensional reconstruction
      of SSc dermal heterotypic fibers confirmed the presence of atypical COLV.
      CONCLUSION: Increased synthesis of abnormal COLV and its correlation with disease
      stage, activity and MRSS suggest that this collagen can be a possible trigger
      involved in the pathogenesis of SSc.

PMID- 22406225
TI  - TB-Lineage: an online tool for classification and analysis of strains of
      Mycobacterium tuberculosis complex.
AB  - This paper formulates a set of rules to classify genotypes of the Mycobacterium
      tuberculosis complex (MTBC) into major lineages using spoligotypes and MIRU-VNTR
      results. The rules synthesize prior literature that characterizes lineages by
      spacer deletions and variations in the number of repeats seen at locus MIRU24
      (alias VNTR2687). A tool that efficiently and accurately implements this rule
      base is now freely available at http://tbinsight.cs.rpi.edu/run_tb_lineage.html.
      When MIRU24 data is not available, the system utilizes predictions made by a
      Naive Bayes classifier based on spoligotype data. This website also provides a
      tool to generate spoligoforests in order to visualize the genetic diversity and
      relatedness of genotypes and their associated lineages. A detailed analysis of
      the application of these tools on a dataset collected by the CDC consisting of
      3198 distinct spoligotypes and 5430 distinct MIRU-VNTR types from 37,066 clinical
      isolates is presented. The tools were also tested on four other independent
      datasets. The accuracy of automated classification using both spoligotypes and
      MIRU24 is >99%, and using spoligotypes alone is >95%. This online rule-based
      classification technique in conjunction with genotype visualization provides a
      practical tool that supports surveillance of TB transmission trends and molecular
      epidemiological studies.

PMID- 22406226
TI  - Hangman BCI: an unsupervised adaptive self-paced Brain-Computer Interface for
      playing games.
AB  - This paper presents a novel user interface suitable for adaptive Brain Computer
      Interface (BCI) system. A customized self-paced BCI architecture is introduced
      where the system combines onset detection system along with an adaptive
      classifier working in parallel. An unsupervised adaptive method based on
      sequential expectation maximization for Gaussian mixture model is employed with
      new timing scheme and an additional averaging step to avoid over-fitting. Sigmoid
      function based post-processing approach is proposed to enhance the classifiers'
      output. The adaptive system is compared to a non-adaptive one and tested on five
      subjects who used the BCI to play the hangman game. The results show significant
      improvement of the True-False difference for all the classes and a reduction in
      the number of steps required to solve the problem.

PMID- 22406227
TI  - Allatotropin, leucokinin and AKH in honey bees and other Hymenoptera.
AB  - In the honey bee no allatotropin gene has been found, even though allatotropin
      stimulates the synthesis of juvenile hormone in this species. We report here that
      honey bees and other Hymenoptera do have a typical allatotropin gene, although
      the peptides predicted have a somewhat different structure from that of other
      insect allatotropins. Polyclonal antisera to honey bee allatotropin reacted with
      material in the neurohemal organs of the segmental nerves of abdominal ganglia.
      We were unable to find the allatotropin peptide using mass spectrometry in
      extracts from these tissues. Thus the expression of this gene in honey bees is
      less important than in other insect species. We also characterized the leucokinin
      gene which similarly appears to be very weakly expressed in worker honey bees.
      Unlike the allatotropin gene, which is conserved within Hymenoptera, the
      leucokinin gene is much more variable in structure and was not found in ants nor
      the parasitic wasp Nasonia vitripennis. The absence of significant expression of
      adipokinetic hormone (AKH) in the honey bee may be due to the existence of a
      second TATA box in the promotor region of the gene, which explains the production
      of an mRNA encoding a putative peptide precursor from which no AKH should be
      released. Such a second TATA box was not found in other Hymenoptera, and may
      therefore be specific for the two Apis species. It is suggested that functional
      disintegration of this important metabolic gene became possible in Apis because
      of the highly evolved social nature of the species.

PMID- 22406229
TI  - C9orf72 repeat expansions in patients with ALS and FTD.

PMID- 22406231
TI  - The role of antioxidants in photoprotection: a critical review.
AB  - Free radicals have long been studied as a contributor to aging and disease
      processes. Endogenous production of radicals from cellular metabolism and
      exogenous sources from ultraviolet radiation and pollution can damage the skin on
      the cellular and tissue levels. Although the body possesses an elegant defense
      system to prevent radical damage, this innate system can be overwhelmed and lead
      to a state of oxidative stress or immunosuppression, and can even trigger
      carcinogenesis. Topical supplementation of antioxidants can provide additional
      protection to neutralize reactive oxygen species from both endogenous and
      exogenous sources. This review will discuss our current understanding of the
      mechanisms of free radical damage and evaluate the potential benefit of topical
      antioxidants in sunscreens and skin care products.

PMID- 22406230
TI  - Sun damage in ultraviolet photographs correlates with phenotypic melanoma risk
      factors in 12-year-old children.
AB  - BACKGROUND: Ultraviolet (UV) photography has been used to motivate sun safety in
      behavioral interventions. The relationship between sun damage shown in UV
      photographs and melanoma risk has not been systematically investigated.
      OBJECTIVE: To examine the relationship between severity of sun damage in UV
      photographs and phenotypic melanoma risk factors in children. METHODS: UV,
      standard visible and cross-polarized photographs were recorded for 585 children.
      Computer software quantified sun damage. Full-body nevus counts, skin color by
      colorimetry, facial freckling, hair and eye color were collected in skin
      examinations. Demographic data were collected in telephone interviews of parents.
      RESULTS: Among 12-year-old children, sun damage shown in UV photographs
      correlated with phenotypic melanoma risk factors. Sun damage was greatest for
      children who were non-Hispanic white and those who had red hair, blue eyes,
      increased facial freckling, light skin and greater number of nevi (all P values <
      .001). Results were similar for standard visible and cross-polarized photographs.
      Freckling was the strongest predictor of sun damage in visible and UV
      photographs. All other phenotypic melanoma risk factors were also predictors for
      the UV photographs. LIMITATIONS: Differences in software algorithms used to score
      the photographs could produce different results. CONCLUSION: UV photographs
      portray more sun damage in children with higher risk for melanoma based on
      phenotype. Therefore sun protection interventions targeting those with greater
      sun damage on UV photographs will target those at higher melanoma risk. This
      study establishes reference ranges dermatologists can use to assess sun damage in
      their pediatric patients.

PMID- 22406228
TI  - Frequency of the C9orf72 hexanucleotide repeat expansion in patients with
      amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional
      study.
AB  - BACKGROUND: We aimed to accurately estimate the frequency of a hexanucleotide
      repeat expansion in C9orf72 that has been associated with a large proportion of
      cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
      METHODS: We screened 4448 patients diagnosed with ALS (El Escorial criteria) and
      1425 patients with FTD (Lund-Manchester criteria) from 17 regions worldwide for
      the GGGGCC hexanucleotide expansion using a repeat-primed PCR assay. We assessed
      familial disease status on the basis of self-reported family history of similar
      neurodegenerative diseases at the time of sample collection. We compared
      haplotype data for 262 patients carrying the expansion with the known Finnish
      founder risk haplotype across the chromosomal locus. We calculated age-related
      penetrance using the Kaplan-Meier method with data for 603 individuals with the
      expansion. FINDINGS: In patients with sporadic ALS, we identified the repeat
      expansion in 236 (7.0%) of 3377 white individuals from the USA, Europe, and
      Australia, two (4.1%) of 49 black individuals from the USA, and six (8.3%) of 72
      Hispanic individuals from the USA. The mutation was present in 217 (39.3%) of 552
      white individuals with familial ALS from Europe and the USA. 59 (6.0%) of 981
      white Europeans with sporadic FTD had the mutation, as did 99 (24.8%) of 400
      white Europeans with familial FTD. Data for other ethnic groups were sparse, but
      we identified one Asian patient with familial ALS (from 20 assessed) and two with
      familial FTD (from three assessed) who carried the mutation. The mutation was not
      carried by the three Native Americans or 360 patients from Asia or the Pacific
      Islands with sporadic ALS who were tested, or by 41 Asian patients with sporadic
      FTD. All patients with the repeat expansion had (partly or fully) the founder
      haplotype, suggesting a one-off expansion occurring about 1500 years ago. The
      pathogenic expansion was non-penetrant in individuals younger than 35 years, 50%
      penetrant by 58 years, and almost fully penetrant by 80 years. INTERPRETATION: A
      common Mendelian genetic lesion in C9orf72 is implicated in many cases of
      sporadic and familial ALS and FTD. Testing for this pathogenic expansion should
      be considered in the management and genetic counselling of patients with these
      fatal neurodegenerative diseases. FUNDING: Full funding sources listed at end of
      paper (see Acknowledgments).

PMID- 22406232
TI  - Ultraviolet photography as a skin cancer risk assessment and intervention tool.

PMID- 22406233
TI  - [The Alice in Wonderland syndrome: an unusual aura in migraine].
AB  - INTRODUCTION: The Alice in Wonderland syndrome consists in a perceptual
      distortion of one's body size and shape. It is rarely encountered in adults,
      where it is mainly associated with migraine with aura and epilepsy. CASE REPORT:
      A 37-year-old woman had had a migraine without aura since puberty. In the months
      following a parturition, she experienced several epidodes of unusual auras
      preceding typical migrainous headache. The aura lasted about 30min and consisted
      in the feeling of lengthening of the trunk and of the four limbs, associated with
      a sensation of well-being. DISCUSSION AND CONCLUSION: Epileptologic and
      experimental data suggest that the Alice in Wonderland syndrome is associated
      with a transient dysfunction of associative somatosensory areas in the parietal
      cortex.

PMID- 22406234
TI  - Soft tissue morphology of the naso-maxillary complex following surgical
      correction of maxillary hypoplasia.
AB  - Orthognathic surgery is undergone to improve facial and dental aesthetics and to
      improve function. Three dimensional (3D) soft tissue analysis based on
      stereophotogrammetry provides a realistic measurement of facial morphology. There
      is a need for objective assessment of surgery outcomes. The study aim was to
      evaluate the 3D naso-maxillary complex soft tissue morphology following Le Fort I
      maxillary advancement and compare the findings with a local reference group. 3D
      images of 112 volunteers were captured using stereophotogrammetry and viewed by 8
      lay people; 40 images (16 males and 24 females) were chosen as the reference
      group to have harmonious facial appearance. The linear and angular measurements
      of this group were compared with 35 patients (19 female and 16 male) who had
      maxillary advancement in the post-surgical group. Facial morphology post-surgery
      was similar to the reference group, except the nasal base width which was wider
      by 2.3mm in males and 2.6mm in females. In the orthognathic group, the females
      had a smaller nasolabial angle by 9.7 degrees  than the reference group. In
      conclusion, 3D imaging is a sensitive tool for analysing facial appearance.
      Compared with a control group, statistical differences were identified in soft
      tissue morphology which should be considered in surgical planning and patient
      consent.

PMID- 22406235
TI  - A comparison of biocompatibility and osseointegration of ceramic and titanium
      implants: an in vivo and in vitro study.
AB  - This study compared the biocompatibility in vitro and the osseointegration in
      vivo of zirconium and titanium implants regarding implant surfaces and the bone
      implant contacts. The different implant surfaces and the biocompatibility of
      zirconium versus titanium implants were determined by vitality and cytotoxic
      tests in vitro. The contact of the osteoblasts to the implant surface was
      determined by scanning electron microscopy (SEM). The in vivo study for
      osseointegration was performed in domestic pigs over 4 and 12 weeks. In each
      animal, 4 zirconium and 4 titanium implants (WhiteSky, BlueSky, Bredent, Germany)
      were inserted in the os frontale and analysed by histomorphometry. Cytotoxicity
      and SEM showed good biocompatibility in relation to the investigated implant
      materials. Histological results showed direct bone-implant contact of the implant
      surfaces. The zirconium implants showed a slight delay in osseointegration in
      terms of bone-implant contact as measured by histomorphometry (after 4 weeks,
      zirconium (59.3 +/- 4.6%) versus titanium (64.1 +/- 3.9%); after 12 weeks,
      zirconium (67.1 +/- 2.3%) versus titanium (73.6 +/- 3.2%). A statistically
      significant difference between the two groups was not observed. The results
      indicated similar biocompatibility and osseointegration for zirconium compared to
      titanium implants.

PMID- 22406236
TI  - Gap26, a connexin mimetic peptide, inhibits currents carried by connexin43
      hemichannels and gap junction channels.
AB  - Connexin mimetic peptides corresponding to short conserved extracellular loop
      sequences of connexins have been used widely as reversible inhibitors of gap
      junctional intercellular communication. These peptides also block movement of ATP
      and Ca(2+) across connexin hemichannels, i.e. hexameric channels yet to dock with
      partners in aligned cells and to generate the gap junction cell-cell conduit. By
      means of electrophysiology, we compared the effects of Gap26, a mimetic peptide
      corresponding to a short linear sequence in the first extracellular loop of
      connexin43, on connexin channel function in HeLa cells expressing connexin43. We
      demonstrate that Gap26 inhibited electrical coupling in cell pairs mediated by
      gap junctions after exposure for 30min. In contrast, Gap26 applied to single
      cells, inhibited hemichannel currents evoked in low Ca(2+) solution with a
      response time of less than 5min. The results further support the view that the
      likely primary and direct inhibitory effect of Gap26 is on connexin hemichannels,
      with gap junctions becoming inhibited later. The mechanism of action of Gap26 in
      blocking hemichannels and gap junction channels is discussed in the context of
      their different functions and locations.

PMID- 22406237
TI  - Identification of reproduction-related proteins and characterization of the
      protein disulfide isomerase A6 cDNA in ovaries of the giant tiger shrimp Penaeus
      monodon.
AB  - Proteomic analysis was carried out for identification of proteins functionally
      involved in ovarian development of the giant tiger shrimp (Penaeus monodon). A
      total of 335 protein spots including 183 spots from vitellogenic (stage II) and
      152 spots from mature (stage IV) ovaries of intact P. monodon broodstock were
      examined. Of these, 75 (40.98%) and 59 (38.82%) spots significantly matched known
      proteins in the databases, respectively. In addition, 270 protein spots including
      167 and 103 spots from respective ovarian stages of eyestalk-ablated broodstock
      were also characterized. A total of 95 (56.89%) and 62 (60.19%) spots matched
      known proteins, respectively. Among differentially expressed reproduction-related
      proteins, the full-length cDNA of protein disulfide isomerase A6 (PmPDIA6) was
      further characterized by RACE-PCR. PmPDIA6 was 1946bp in length containing an
      open reading frame (ORF) of 1293bp corresponding to a polypeptide of 430 amino
      acids. PmPDIA6 was up-regulated at stage III ovaries in intact shrimp (P<0.05).
      Interestingly, eyestalk ablation resulted in a lower expression level of PmPDIA6
      in each stage of ovarian development compared to that of intact broodstock
      (P<0.05). Results in this study clearly indicated the potential of cellular
      proteomic studies and gene expression analysis for identification of
      proteins/genes differentially expressed during ovarian development of P. monodon.

PMID- 22406238
TI  - Commentary to 'Outcome after 7 years of carotid artery stenting and
      endarterectomy in Sweden - single centre and national results'.

PMID- 22406239
TI  - Synergistic antidepressant-like action of gaboxadol and escitalopram.
AB  - According to current theories on the etiopathogenesis and pathophysiology of
      depression, both GABAergic and monoaminergic transmitter systems are perturbed.
      Consequently, the present study addressed the putative antidepressant action of
      the sedative-hypnotic GABAA receptor agonist, gaboxadol, separately and in
      combination with the selective serotonin reuptake inhibitor (SSRI) escitalopram.
      The rat chronic mild stress model was used to test the chronic antidepressant
      properties of gaboxadol in this depression model. Sucrose intake used as a read
      out on anhedonic-like behavior indicated that the drug response rate for
      gaboxadol (5 mg/kg/day, i.p.) was similar to that measured for escitalopram (5
      mg/kg/day, i.p.), however, the rate increased when the two drugs were co
      administered, suggesting a synergistic action. Using in vivo electrophysiological
      recordings in dorsal raphe nucleus (DRN) of anesthetised rats, the present
      results showed that one week treatment with gaboxadol (5 mg/kg/day, i.p.) or with
      escitalopram (5 mg/kg/day, i.p.), followed by a 24 h washout period, did not
      affect DRN 5-HT neuronal firing per se, but in rats treated with both drugs for
      one week, the firing rate of DRN 5-HT neurons was significantly increased.
      Immunohistochemical estimations of cell proliferation in the hippocampal dentate
      gyrus did not reveal any effect of gaboxadol on chronic mild stressed rats,
      indicating that neurogenesis per se is not systematically associated with
      recovery from anhedonic-like behavior. Taken together, our data reveal for the
      first time an antidepressant action of gaboxadol and indicate a synergistic
      mechanism, regarding rapid onset of action and efficacy, when co-administered
      with escitalopram.

PMID- 22406240
TI  - Genetic polymorphisms in the opioid receptor mu1 gene are associated with changes
      in libido and insomnia in methadone maintenance patients.
AB  - Methadone, a synthetic racemic opioid that primarily works as a MU-opioid
      receptor (OPRM1) agonist, is commonly used for the treatment of heroin addiction.
      Genetic association studies have reported that the OPRM1 gene is involved in the
      physiology of heroin and alcohol addiction. Our current study is designed to test
      the hypothesis that genetic polymorphisms in the OPRM1 gene region are associated
      with methadone dosage, plasma concentrations, treatment responses, adverse
      reactions and withdrawal symptoms in a methadone maintenance treatment (MMT)
      cohort from Taiwan. Fifteen OPRM1 single nucleotide polymorphisms (SNPs) were
      selected and genotyped using DNA samples from 366 MMT patients. The plasma
      concentrations of methadone and its metabolite were measured by high performance
      liquid chromatography. The results obtained using dominant model analysis
      indicate that the OPRM1 SNPs rs1074287, rs6912029, rs12209447, rs510769,
      rs3798676, rs7748401, rs495491, rs10457090, rs589046, rs3778152, rs563649, and
      rs2075572 are significantly associated with change-in-libido side effects
      (adjusted p<0.042). Using recessive model analysis, these SNPs were also found to
      be significantly associated with insomnia side effects in this cohort (p<0.009).
      The significance of the insomnia findings was mainly contributed by a subgroup of
      patients who had a positive urine morphine test (p<0.022), and by individuals who
      did not use benzodiazepine hypnotics (p<0.034). Our current data thus suggest
      that genetic polymorphisms in OPRM1 may influence the change-in-libido and
      insomnia side effects sometimes found in MMT patients.

PMID- 22406241
TI  - Assessment of heavy metal contamination in Hindon River sediments: a chemometric
      and geochemical approach.
AB  - The aim of this study was to assess the level of heavy metals (Cd, Cr, Cu, Fe,
      Mn, Ni, Pb, and Zn) in the surface sediments of the Hindon River, India that
      receives both treated and untreated municipal and industrial discharges generated
      in and around Ghaziabad, India. Mean metals concentrations (mg kg(-1)) were in
      the range of; Cu: 21.70-280.33, Cd: 0.29-6.29, Fe: 4151.75-17318.75, Zn: 22.22.50
      288.29, Ni: 13.90-57.66, Mn: 49.55-516.97, Cr: 17.48-33.70 and Pb: 27.56-313.57
      respectively. Chemometric analysis was applied to identify contribution sources
      by heavy metals while geochemical approaches (enrichment factor and geo
      accumulation index) were exploited for the assessment of the enrichment and
      contamination level of heavy metals in the river sediments. Chemometric analysis
      suggested anthropic origin of Cu, Cd, Pb, Zn, and Ni while Fe showed lithogenic
      origin. Mn and Cr was associated and controlled by mixed origin. Geochemical
      approach confirms the anthropogenic influence of heavy metal pollution in the
      river sediments. The study suggests that a complementary approach that integrates
      chemometric analysis, sediment quality criteria, and geochemical investigation
      should be considered in order to provide a more accurate appraisal of the heavy
      metal pollution in river sediments. Consequently, it may serve to undertake and
      design effective strategies and remedial measures to prevent further
      deterioration of the river ecosystem in future.

PMID- 22406242
TI  - A comparative study of the electrochemical oxidation of the herbicide tebuthiuron
      using boron-doped diamond electrodes.
AB  - The thiadiazolylurea derivative tebuthiuron (TBH) is commonly used as an
      herbicide even though it is highly toxic to humans. While various processes have
      been proposed for the removal of organic contaminants of this type from
      wastewater, electrochemical degradation has shown particular promise. The aim of
      the present study was to investigate the electrochemical degradation of TBH using
      anodes comprising boron-doped (5000 and 30,000 ppm) diamond (BDD) films deposited
      onto Ti substrates operated at current densities in the range 10-200 mA cm(-2).
      Both anodes removed TBH following a similar pseudo first-order reaction kinetics
      with k(app) close to 3.2 * 10(-2) min(-1). The maximum mineralization efficiency
      obtained was 80%. High-pressure liquid chromatography with UV-VIS detection
      established that both anodes degraded TBH via similar intermediates. Ion
      chromatography revealed that increasing concentrations of nitrate ions (up to 0.9
      ppm) were formed with increasing current density, while the formation of nitrite
      ions was observed with both anodes at current densities >= 150 mA cm(-2). The BDD
      film prepared at the lower doping level (5000 ppm) was more efficient in
      degrading TBH than its more highly doped counterpart. This unexpected finding may
      be explained in terms of the quantity of impurities incorporated into the diamond
      lattice during chemical vapor deposition.

PMID- 22406243
TI  - Spectroscopic (FT-IR, FT-Raman and 1H and 13C NMR) and theoretical in MP2/6
      311++G(d,p) and B3LYP/6-311++G(d,p) levels study of benzenesulfonic acid and
      alkali metal benzenesulfonates.
AB  - The FT-IR, FT-Raman and NMR ((1)H and (13)C) spectra of benzenesulfonic acid as
      well as lithium, sodium, potassium, rubidium and caesium benzenesulfonates were
      registered, assigned and compared. The molecular structures of ligand and alkali
      metal salts were discussed. On the basis of quantum mechanical calculations in
      MP2/6-311++G(d,p) and B3LYP/6-311++G(d,p) levels the geometric parameters,
      infrared spectra, NMR spectra, the magnetic and geometric aromaticity indices for
      acid and alkali metal benzenesulfonates and benzoates were obtained. The effect
      of alkali metal ions on the electronic charge distribution of benzenesulfonic
      acid was studied and compared with the alkali metal benzoates and benzoic acid.

PMID- 22406244
TI  - The administration of oxytocin during early reperfusion, dose-dependently
      protects the isolated male rat heart against ischemia/reperfusion injury.
AB  - In our previous study, the administration of oxytocin (OT) could precondition the
      heart against ischemia/reperfusion injury. In this study, to investigate the
      cardiac postconditioning effect of oxytocin, isolated rat hearts were mounted on
      a Langendorff perfusion apparatus. In all groups, the hearts underwent 30 min of
      regional ischemia followed by 120 min of reperfusion. In the ischemia/reperfusion
      (IR) group, ischemia and reperfusion was induced. In the ischemic
      postconditioning (Ipost) group, hearts underwent 6 cycles of 10s reperfusion and
      10s ischemia at the beginning of reperfusion. In the other groups (III-IX), OT
      was perfused 5 min before the onset of reperfusion and continued for 25 min with
      following doses (Molar): 10(-12), 5 * 10(-12), 8 * 10(-12), 10(-11), 2 * 10(-11),
      5 * 10(-11), and 10(-10). The infarct size and coronary effluent levels of
      creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and malondialdehyde (MDA)
      were calculated at the end of reperfusion. The infarct size decreased
      considerably in Ipost group compared to IR group (P<0.05). Also, the infusion of
      oxytocin by doses of 8 * 10(-12)M, 10(-11)M and 2 * 10(-11)M dose-dependently
      reduced infarct size (P<0.05) significantly compared to the IR group. LDH level
      in coronary effluent was markedly decreased in Ipost group and treatment with
      oxytocin by doses of 8 * 10(-12)M, 10(-11)M, 2 * 10(-11)M and 5 * 10(-11)M
      (P<0.05) compared to IR group. Ipost, OT 2 * 10(-11)and 10(-11)M significantly
      decreased CK-MB level (P<0.05). Ipost, OT 8 * 10(-12), 10(-11) and 2 * 10(-11)M
      significantly decreased MDA level as compared to IR group. Our study shows that
      oxytocin dose-dependently exerts cardiac postconditioning.

PMID- 22406245
TI  - A note on Melia toosendan Siebold & Zucc.

PMID- 22406246
TI  - An A-T linker adapter polymerase chain reaction method for chromosome walking
      without restriction site cloning bias.
AB  - A-T linker adapter polymerase chain reaction (PCR) was modified and employed for
      the isolation of genomic fragments adjacent to a known DNA sequence. The
      improvements in the method focus on two points. The first is the modification of
      the PO(4) and NH(2) groups in the adapter to inhibit the self-ligation of the
      adapter or the generation of nonspecific products. The second improvement is the
      use of the capacity of rTaq DNA polymerase to add an adenosine overhang at the 3'
      ends of digested DNA to suppress self-ligation in the digested DNA and
      simultaneously resolve restriction site clone bias. The combination of
      modifications in the adapter and in the digested DNA leads to T/A-specific
      ligation, which enhances the flexibility of this method and makes it feasible to
      use many different restriction enzymes with a single adapter. This novel A-T
      linker adapter PCR overcomes the inherent limitations of the original ligation
      mediated PCR method such as low specificity and a lack of restriction enzyme
      choice. Moreover, this method also offers higher amplification efficiency,
      greater flexibility, and easier manipulation compared with other PCR methods for
      chromosome walking. Experimental results from 143 Arabidopsis mutants illustrate
      that this method is reliable and efficient in high-throughput experiments.

PMID- 22406247
TI  - Generation of reporter plasmids containing defined base modifications in the DNA
      strand of choice.
AB  - Physiological effects of DNA bases other than A, G, C, and T as well as ways of
      removal of such bases from genomes are studied intensely. Methods for targeted
      insertion of modified bases into DNA, therefore, are highly demanded in the
      fields of DNA repair and epigenetics. This article describes efficient procedures
      for incorporation of modified DNA bases into a plasmid-borne enhanced green
      fluorescent protein (EGFP) gene. The procedure exploits excision of a stretch of
      18 nt from either the transcribed or nontranscribed DNA strand with the help of
      the sequence-specific nicking endonucleases Nb.Bpu10I and Nt.Bpu10I. The excised
      single-stranded oligonucleotide is then swapped for a synthetic DNA strand
      containing a desired base modification. Base modifications that form Watson-Crick
      type base pairs were efficiently incorporated into plasmid DNA by a
      straightforward strand exchange, which was achieved by local melting in the
      presence of large excesses of the synthetic oligonucleotides and reannealing
      followed by ligation. Base modifications that cause significant distortions of
      the normal DNA structure, such as thymine glycol and uracil mispaired with
      guanine, failed to produce high yields of direct strand exchange but could still
      be incorporated very efficiently when the excised fragment was depleted in an
      intermediate step.

PMID- 22406248
TI  - Binding activity of avidin to the biotin within mesoporous silica materials for
      bioanalytical applications.
AB  - It has been reported that the activity of protein improved when it was adsorbed
      inside the pores of mesoporous silica (MPS). The current study investigated the
      activity of immobilized avidin to the biotin on MPS with various pore sizes
      (diameter=2.4-45.0 nm). The binding amount of immobilized avidin to biotin is 123
      to 160 ng biotin/10 MUg avidin on 2.7- to 5.4-nm pore MPS, but that on 12- to 45
      nm pore MPS was markedly decreased (33-42 ng biotin/10 MUg). Moreover, the
      binding amount was approximately 2- and 3-fold higher on the glycidoxypropyl
      (Gly)-functionalized 5.4- and 45-nm pore MPS in comparison with methyl (Me)
      functionalized 5.4- and 45-nm pore MPS, respectively. Furthermore, avidin
      immobilized in native and Gly-grafted 45-nm pore MPS retained more than 70% and
      50% binding activity to biotin, respectively, after incubating at 90 degrees C
      for 3 h. In contrast, the activity was greatly reduced in the native and Gly
      grafted 5.4-nm pore MPS under the same conditions (<36.9%). The immobilization
      also protected against effects of 0.01 M HCl and 50% MeOH; all of immobilized
      avidin proteins showed high activity (>50%) with biotin compared with that
      observed with free avidin (MeOH [<18.2%] and HCl [<32.7%]).

PMID- 22406249
TI  - Evaluation of the angiogenesis inhibitor KR-31831 in SKOV-3 tumor-bearing mice
      using (64)Cu-DOTA-VEGF(121) and microPET.
AB  - KR-31831 ((2R,3R,4S)-6-amino-4-[N-(4-chloropheyl)-N-(1H-imidazol-2ylmethyl)amino]
      3-hydroxyl-2-methyl-2-dimethoxymethyl-3,4-dihydro-2H-1-benzopyran), an
      angiogenesis inhibitor, was evaluated in tumor-bearing mice using molecular
      imaging technology. Pre-treatment microPET images were acquired on SKOV-3 cell
      implanted nude mice after injection with (64)Cu-DOTA-VEGF(121). KR-31831 (50
      mg/kg) was then injected intraperitoneally into the treatment group (n=3), while
      injection vehicle was injected into the control (n=4) and blocking (n=3) groups.
      After injections occurred daily for 28 days, all groups of mice underwent post
      treatment microPET imaging after injection with (64)Cu-DOTA-VEGF(121). The post
      treatment images showed high tumor uptake in the control group and reduced tumor
      uptake in both the blocking and treatment groups. ROI analysis of the tumor
      images revealed 6.25%+/-1.18% ID/g at 1 h, 6.55%+/-0.69% ID/g at 2 h, and 4.68%+/
      0.63% ID/g at 16 h in the control group; 3.87%+/-0.45% ID/g at 1 h, 4.50%+/-0.44%
      ID/g at 2 h, and 3.63%+/-0.25% ID/g at 16 h in the blocking group; and 4.03%+/
      0.74% ID/g at 1 h, 4.37%+/-0.67% ID/g at 2 h, and 3.83%+/-0.90% ID/g at 16 h in
      the treatment group. Biodistribution obtained after the post-treatment microPET
      imaging also demonstrated high tumor uptake (3.74%+/-0.27% ID/g) in the control
      group and reduced uptakes in both the blocking group (2.69%+/-0.73% ID/g, P<.05)
      and the treatment group (3.11%+/-0.25% ID/g, P<.05), which correlated well with
      microPET imaging data. Immunofluorescence analysis showed higher levels of VEGFR2
      and CD31 expressions in tumor tissues of the control and blocking groups than in
      tumor tissues of the treatment group. These results suggest that the
      antiangiogenic activity of KR-31831 is mediated through VEGFR2 and microPET
      serves as a useful molecular imaging tool for evaluation of a newly developed
      angiogenesis inhibitor, KR-31831.

PMID- 22406250
TI  - Short intermittent hypoxic exposures augment ventilation but do not alter
      regional cerebral and muscle oxygenation during hypoxic exercise.
AB  - This study investigated the effects of four exposures to normobaric hypoxia (SIH
      group; FIO2 = 0.120, N=10) or placebo-control normoxia (Control group; FIO2 =
      0.209, N=9) on cardio-respiratory responses to hypoxic exercise. Before and after
      the exposures all subjects performed a constant power test (CP) to exhaustion in
      hypoxia FIO2 = 0.120 at a work load corresponding to 75% of previously determined
      normoxic VO2 peak. Arterial oxygen saturation (SPO2) and minute ventilation
      (V(E)) were measured continuously. NIRS was used to monitor regional changes in
      oxygenated, de-oxygenated and total hemoglobin concentrations of the frontal
      cortex, vastus lateralis and serratus anterior. Although neither group improved
      CP time, the SIH group exhibited increases in both V(E) (+15%; P<0.05) and SPO2
      (+4%; P<0.05) after intermittent hypoxia. No physiologically significant
      differences were observed during exercise in vastus lateralis, serratus anterior
      and cerebral oxygenation between groups and testing periods. These data suggest
      that normobaric SIH enhances hypoxic exercise V(E) and SPO2 without affecting
      regional oxygenation or time to exhaustion.

PMID- 22406251
TI  - Validation of the Greek version of Confusion Assessment Method for the Intensive
      Care Unit (CAM-ICU).
AB  - OBJECTIVES: Delirium is associated with the most adverse outcomes in critically
      ill patients but it is often undiagnosed and untreated. The Confusion Assessment
      Method for Intensive Care Unit (CAM-ICU) is widely used for delirium assessment.
      This scale, however, has not been translated and validated into the Greek
      language. This paper is a report of the translation and validation of the CAM-ICU
      into Greek. RESEARCH METHODOLOGY: The applicability and validity of CAM-ICU was
      tested in two Greek general ICUs. Each patient was included in the study only
      once. Inter-rater reliability and concurrent validity of both raters compared to
      the gold standard (DSM-IV) was calculated. RESULTS: Study sample consisted of 71
      patients. Based on psychiatric diagnosis the prevalence of delirium was 33.8%.
      Compared to the reference standard for diagnosing delirium, the two study raters
      who used the CAM-ICU had sensitivities of 87.5% and 79.0%, specificities of 91.0%
      and 87.0%, and good inter-rater reliability (kappa=0.75). Cronbach's alpha was
      0.84 (95% CI 0.77-0.89). The mean CAM-ICU administration time was 6 minutes and
      30 seconds. CONCLUSION: CAM-ICU seems to be a valid and reliable instrument for
      delirium detection in Greek intensive care patients, which can be easily
      incorporated in every day clinical practice after appropriate training.

PMID- 22406252
TI  - End of life in intensive care: is transfer home an alternative?
AB  - The past decade has witnessed an increased focus on improving the quality of end
      of life care internationally. This has resulted in the development of specific
      health policy work streams to support patient choice and improve standards of
      care and patient experience. One concept well explored in areas outside of
      critical care is that of home care at the end of life. This paper seeks to
      challenge assumptions and practices about the options for transferring the
      critically ill patient home at end of life. As a piece of collaborative writing
      from a bereaved family member and critical care nursing team, this paper explores
      care given to one gentleman at the end of his life. In this, his journey is
      detailed, the decisions made are outlined and the experience for him and his
      family are examined with a retrospective narrative account from his wife that is
      woven throughout the paper. In this paper, we are not asserting that transfer
      home at end of life is desirable or feasible for all critically ill patients. We
      are challenging practitioners to consider when and how the initiative of
      transferring critically ill patients home at end of life, may occur.

PMID- 22406253
TI  - Functional polymorphisms in the LTF gene and risk of coronary artery stenosis.
AB  - Plasma lactoferrin concentrations are increased in patients with coronary artery
      stenosis. We investigated the effects of LTF gene polymorphisms in 305 healthy
      blood donors and their associations with coronary artery stenosis in 236 patients
      admitted for coronary angiography. Lactoferrin concentrations were determined by
      enzyme immunoassay. Genotyping was performed by polymerase chain reaction and DNA
      sequencing of LTF exons 2 and 4. In the blood donors, the deletion variant of
      rs10662431 and the G allele of rs1126478 were associated with higher plasma
      lactoferrin concentrations. The G allele of rs1126478 was more frequent in
      patients with significant coronary artery stenosis (p = 0.018, p value limit for
      significance by permutation = 0.030). The association remained significant in
      logistic regression with adjustment for clinical risk factors (odds ratio 2.485
      [95% confidence interval 1.116-5.536], p = 0.026), but was weakened upon the
      inclusion of plasma lactoferrin (odds ratio 2.295 [0.949-5.550], p = 0.064).
      Current evidence indicates that rs1126478 affects the antibacterial effect of
      lactoferrin and that lactoferrin is involved in lipid metabolism. The
      relationships among lactoferrin genotypes, lactoferrin concentrations, and
      clinical factors on the risk for atherosclerosis are not fully understood, but
      the G allele of rs1126478 seems to have a detrimental effect in a European
      population.

PMID- 22406254
TI  - C4A deficiency in children and adolescents with recurrent respiratory infections.
AB  - Increased susceptibility to recurrent viral and bacterial respiratory infections
      in children and young adults is not well understood. To evaluate the role of
      complement factor C4 in the defense against respiratory infections, we studied
      complement factor C4 allotypes C4A and C4B and copy numbers of C4A and C4B genes
      in 84 children and young adults with recurrent acute otitis media, sinusitis, or
      pneumonia and in 74 healthy controls. The occurrence of C4A gene deficiency was
      significantly higher in patients compared with controls (26% vs 14%, p = 0.048).
      Girls predominated in the group of patients with C4A deficiency (73% girls and
      27% boys, p = 0.004). The lectin pathway of complement was more often
      functionally impaired in patients with C4A deficiency than in patients with no
      C4A deficiency (41% vs 13%, p = 0.033). Classical and alternative pathways were
      normal in individuals with C4 null alleles. C4A deficiency is 1 of the minor
      defects of the innate immunity that may predispose children and young adults to
      recurrent respiratory infections. C4 gene testing should be added to the list of
      investigations when the cause for recurrent acute otitis media, maxillary
      sinusitis, or pneumonia in children and young adults is sought.

PMID- 22406255
TI  - Differential peptide binding to CD40 evokes counteractive responses.
AB  - The antigen-presenting cell-expressed CD40 is implied in the regulation of
      counteractive immune responses such as induction of pro-inflammatory and anti
      inflammatory cytokines interleukin (IL)-12 and IL-10, respectively. The mechanism
      of this duality in CD40 function remains unknown. Here, we investigated whether
      such duality depends on ligand binding. Based on CD40 binding, we identifed two
      dodecameric peptides, peptide-7 and peptide-19, from the phage peptide library.
      Peptide-7 induces IL-10 and increases Leishmania donovani infection in
      macrophages, whereas peptide-19 induces IL-12 and reduces L. donovani infection.
      CD40-peptide interaction analyses by surface plasmon resonance and atomic force
      microscopy suggest that the functional differences are not associated with the
      studied interaction parameters. The molecular dynamic simulation of the CD40
      peptides interaction suggests that these two peptides bind to two different
      places on CD40. Thus, we suggest for the first time that differential binding of
      the ligands imparts functional duality to CD40.

PMID- 22406257
TI  - Can magnesium supplementation reduce seizures in people with epilepsy? A
      hypothesis.
AB  - Magnesium is required for over 300 enzyme systems and is critical for many
      cellular functions including oxidative phosphorylation, glycolysis, DNA
      transcription and protein synthesis. Studies suggest that the modern Western diet
      and lifestyle may lead to magnesium deficiency, and this appears to be associated
      with a wide range of medical conditions. Magnesium deficiency decreases seizure
      thresholds in animal models of epilepsy and indeed low magnesium concentration in
      the perfusate is a common method of generating spontaneous epileptiform
      discharges from rat hippocampal slices. Magnesium is a potential modulator of
      seizure activity because of its ability to antagonize excitation through the N
      methyl-d-aspartate receptor. Some studies have shown that people with epilepsy
      have lower magnesium levels than people without epilepsy. There are case reports
      of seizures being controlled with magnesium supplementation in people with
      specific conditions, and recently in an open randomized trial, children with
      infantile spasms responded better to adrenocorticotropic hormone (ACTH) plus
      magnesium than to ACTH alone. We hypothesise that magnesium supplementation can
      reduce seizures in people with epilepsy. This hypothesis can be tested in a
      controlled randomised supplementation trial. If proven, magnesium supplementation
      needs to be considered in the overall management of people with refractory
      epilepsy.

PMID- 22406259
TI  - Localization of mRNAs encoding human mitochondrial oxidative phosphorylation
      proteins.
AB  - The mitochondrial oxidative phosphorylation (OXPHOS) proteins are encoded by both
      nuclear and mitochondrial DNA. The nuclear-encoded OXPHOS mRNAs have specific
      subcellular localizations, but little is known about which localize near
      mitochondria. Here, we compared mRNAs in mitochondria-bound polysome fractions
      with those in cytosolic, free polysome fractions. mRNAs encoding hydrophobic
      OXPHOS proteins, which insert into the inner membrane, were localized near
      mitochondria. Conversely, OXPHOS gene which mRNAs were predominantly localized in
      cytosol had less than one transmembrane domain. The RNA-binding protein Y-box
      binding protein-1 is localized at the mitochondrial outer membrane and bound to
      the OXPHOS mRNAs. Our findings offer new insight into mitochondrial co
      translational import in human cells.

PMID- 22406258
TI  - Mistic and TarCF as fusion protein partners for functional expression of the
      cannabinoid receptor 2 in Escherichia coli.
AB  - G protein coupled receptors (GPCRs) are key players in signal recognition and
      cellular communication making them important therapeutic targets. Large-scale
      production of these membrane proteins in their native form is crucial for
      understanding their mechanism of action and target-based drug design. Here we
      report the overexpression system for a GPCR, the cannabinoid receptor subtype 2
      (CB2), in Escherichia coli C43(DE3) facilitated by two fusion partners: Mistic,
      an integral membrane protein expression enhancer at the N-terminal, and TarCF, a
      C-terminal fragment of the bacterial chemosensory transducer Tar at the C
      terminal of the CB2 open reading frame region. Multiple histidine tags were added
      on both ends of the fusion protein to facilitate purification. Using individual
      and combined fusion partners, we found that CB2 fusion protein expression was
      maximized only when both partners were used. Variable growth and induction
      conditions were conducted to determine and optimize protein expression. More
      importantly, this fusion protein Mistic-CB2-TarCF can localize into the E. coli
      membrane and exhibit functional binding activities with known CB2 ligands
      including CP55,940, WIN55,212-2 and SR144,528. These results indicate that this
      novel expression and purification system provides us with a promising strategy
      for the preparation of biologically active GPCRs, as well as general application
      for the preparation of membrane-bound proteins using the two new fusion partners
      described.

PMID- 22406260
TI  - Future strategies in microbicide development.
AB  - The reduction in human immunodeficiency virus (HIV) infection in women
      demonstrated by pericoital use of tenofovir gel has encouraged the continued
      development of microbicides. Novel approaches include new ways to deliver
      tenofovir, as well as products that contain different antiretroviral drugs,
      either as single agents or as combinations of antiretroviral drugs. Indeed,
      emphasis has renewed on the development of multipurpose prevention technologies,
      products designed to address multiple sexually transmitted infections. Dual
      purpose contraceptive antiretroviral products are also being designed to prevent
      HIV and pregnancy. Since consistent and correct use of these products will be
      critical to their effectiveness, the active pharmaceutical ingredients must be
      delivered in acceptable vaginal dosage forms, such as gels, films and sustained
      release vaginal rings. The development of different dosage forms will help ensure
      that women can find a method to protect themselves from HIV, pregnancy, and
      potentially other sexually transmitted infections.

PMID- 22406261
TI  - The partial AlloDerm sling: reducing allograft costs associated with breast
      reconstruction.
AB  - BACKGROUND: Many surgeons now incorporate Acellular Dermal Matrix (ADM) into
      expander-based breast reconstruction. ADM is safe, provides full expander
      coverage, eliminates the need for additional muscular dissection and has improved
      aesthetic outcomes. However, its use increases surgical costs. Whether this cost
      is offset by decreased operative times or a reduced number of revision procedures
      is unknown. METHODS: We have developed a new technique that minimises the amount
      of ADM required in many patients. The 'partial sling' approach has been used for
      145 consecutive patients (197 breasts) by a single surgeon from 2007 to 2010.
      After mastectomy, any portion of the pectoralis major insertion at, or <1 cm
      from, the planned inframmary fold is left intact and becomes the inferior margin
      of the expander pocket. The minimal size of ADM required is then determined by
      measuring from the pectoralis to the lateral breast margin. In this study, we
      exclusively used AlloDerm. Preoperative breast measurements, intra-operative fill
      volume, time to exchange procedure, number of expansion procedures and
      complications were recorded for all patients. RESULTS: Patients were grouped
      according to the surface area (cm(2)) of ADM required. Good aesthetic outcomes
      were obtained in all groups. Two groups had a significant difference in intra
      operative fill volumes but this did not correlate to an increase in the number of
      expansion procedures required. Of 197 reconstructed breasts less than 64 cm(2) of
      ADM was used for 40 breasts (20%). CONCLUSIONS: The partial AlloDerm sling can
      minimise the costs associated with ADM use in breast reconstruction for many
      patients without increasing complications or altering aesthetic outcomes.

PMID- 22406262
TI  - A general framework for analysing multiplayer games in networks using territorial
      interactions as a case study.
AB  - Recently, models of evolution have begun to incorporate structured populations,
      including spatial structure, through the modelling of evolutionary processes on
      graphs (evolutionary graph theory). One limitation of this otherwise quite
      general framework is that interactions are restricted to pairwise ones, through
      the edges connecting pairs of individuals. Yet, many animal interactions can
      involve many players, and theoretical models also describe such multiplayer
      interactions. We shall discuss a more general modelling framework of interactions
      of structured populations with the focus on competition between territorial
      animals, where each animal or animal group has a "home range" which overlaps with
      a number of others, and interactions between various group sizes are possible.
      Depending upon the behaviour concerned we can embed the results of different
      evolutionary games within our structure, as occurs for pairwise games such as the
      Prisoner's Dilemma or the Hawk-Dove game on graphs. We discuss some examples
      together with some important differences between this approach and evolutionary
      graph theory.

PMID- 22406263
TI  - S1P2 receptor mediates sphingosine-1-phosphate-induced fibronectin expression via
      MAPK signaling pathway in mesangial cells under high glucose condition.
AB  - Accumulation of extracellular matrix including fibronectin in mesangium is one of
      the major pathologic characteristics in diabetic nephropathy. In the current
      study, we explored role of sphingosine-1-phosphate (S1P) receptor in fibronectin
      expression and underlying molecular mechanism. Among five S1P receptors the mRNA
      level of S1P2 receptor was the most abundant in kidney of diabetic rats and
      mesangial cells under high glucose condition. S1P augmentation of fibronectin was
      significantly inhibited by S1P2 receptor antagonist JTE-013 and S1P2-siRNA. S1P
      stimulated fibronectin expression was remarkably blocked by ERK1/2 inhibitor
      PD98059 and p38MAPK inhibitor SB203580. Phospho-ERK1/2 and phospho-p38MAPK level
      induced by S1P were markedly abrogated by JTE-013 and S1P2-siRNA. In conclusion,
      S1P2 receptor was significantly up-regulated under diabetic condition. S1P2
      receptor mediated fibronectin expression through the activation of S1P-S1P2-MAPK
      (ERK1/2 and p38MAPK) axis in mesangial cells under high glucose condition,
      suggesting that it might be a potential therapeutic target for diabetic
      nephropathy treatment.

PMID- 22406264
TI  - Protein disulfide isomerase-mediated disulfide bonds regulate the gelatinolytic
      activity and secretion of matrix metalloproteinase-9.
AB  - Matrix metalloproteinase-9 (MMP-9) is one of the major MMPs that can degrade
      extracellular matrix. Besides normal physiological functions, MMP-9 is involved
      in metastasis and tumor angiogenesis. Although several inhibitors of MMP-9 have
      been identified, in vivo regulators of MMP-9 activation are unknown. In the
      present study we intended to investigate novel therapeutic target protein(s) that
      regulate MMP-9 activation and/or secretion. We have identified protein disulfide
      isomerase as a novel upstream regulator of MMP-9. Mass spectrometric analysis of
      post-translational modification in MMP-9 confirmed six disulfide bonds in the
      catalytic domain and one disulfide bond in the hemopexin domain of MMP-9.
      Establishment of cells that overexpressed wild-type and mutant forms of MMP-9
      revealed that 'cysteine-switch' and disulfide bonds within the catalytic domain
      are necessary for the secretion and intracellular trafficking of MMP-9. However,
      the disulfide bond of the hemopexin domain and other cysteines have no
      significant role in secretion. These insights into the secretion of MMP-9
      constitute the basis for the development of potential drugs against metastasis.

PMID- 22406265
TI  - The central role of initiator caspase-9 in apoptosis signal transduction and the
      regulation of its activation and activity on the apoptosome.
AB  - Key structural and catalytic features are conserved across the entire family of
      cysteine-dependent aspartate-specific proteases (caspases). Of the caspases
      involved in apoptosis signal transduction, the initiator caspases-2, -8 and -9
      are activated at multi-protein activation platforms, and activation is thought to
      involve homo-dimerisation of the monomeric zymogens. Caspase-9, the essential
      initiator caspase required for apoptosis signalling through the mitochondrial
      pathway, is activated on the apoptosome complex, and failure to activate caspase
      9 has profound pathophysiological consequences. Here, we review the pertinent
      literature on which the currently prevalent understanding of caspase-9 activation
      is based, extend this view by insight obtained from recent structural and kinetic
      studies on caspase-9 signalling, and describe an emerging model for the
      regulation of caspase-9 activation and activity that arise from the complexity of
      multi-protein interactions at the apoptosome. This integrated view allows us to
      postulate and to discuss functional consequences for caspase-9 activation and
      apoptosis execution that may take centre stage in future experimental cell
      research on apoptosis signalling.

PMID- 22406266
TI  - Spindle positioning in mammalian oocytes.
AB  - To preserve the maternal stores accumulated during oogenesis for further embryo
      development, oocytes divide asymmetrically which minimizes the volume of
      cytoplasm lost with each set of haploid genome. To ensure asymmetric division to
      occur, oocytes have to position their division spindle asymmetrically as well as
      tailor the size of daughter cells to the chromatin mass. In this review, we will
      discuss the recent advances in the field, with emphasis on the control mechanisms
      involved in meiotic spindle positioning in mammalian oocytes.

PMID- 22406267
TI  - Lipid-antigen presentation by CD1d(+) B cells is essential for the maintenance of
      invariant natural killer T cells.
AB  - B cells perform many immunological functions, including presenting lipid antigen
      to CD1d-restricted invariant natural killer T (iNKT) cells, known to contribute
      to maintaining tolerance in autoimmunity. Patients with systemic lupus
      erythematous (SLE) display dysregulated B cell responses and reduced peripheral
      iNKT cell frequencies. The significance of these defects and how they relate to
      SLE pathogenesis remain elusive. We report that B cells are essential for iNKT
      cell expansion and activation in healthy donors but fail to exert a similar
      effect in SLE patients. Defective B cell-mediated stimulation of iNKT cells in
      SLE patients was associated with altered CD1d recycling, a defect recapitulated
      in B cells from healthy donors after stimulation with interferon-alpha (IFN
      alpha) and anti-immunoglobulin (Ig). iNKT cell number and function were restored
      in SLE patients responding to anti-CD20 treatment upon normalization of CD1d
      expression exclusively in repopulated immature B cells. We propose that healthy B
      cells are pivotal for iNKT cell homeostasis.

PMID- 22406268
TI  - Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of
      latent viral reservoir after virus reactivation.
AB  - Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication but
      cannot eliminate the virus because HIV-1 establishes latent infection.
      Interruption of HAART leads to a rapid rebound of viremia, so life-long treatment
      is required. Efforts to purge the latent reservoir have focused on reactivating
      latent proviruses without inducing global T cell activation. However, the killing
      of the infected cells after virus reactivation, which is essential for
      elimination of the reservoir, has not been assessed. Here we show that after
      reversal of latency in an in vitro model, infected resting CD4(+) T cells
      survived despite viral cytopathic effects, even in the presence of autologous
      cytolytic T lymphocytes (CTLs) from most patients on HAART. Antigen-specific
      stimulation of patient CTLs led to efficient killing of infected cells. These
      results demonstrate that stimulating HIV-1-specific CTLs prior to reactivating
      latent HIV-1 may be essential for successful eradication efforts and should be
      considered in future clinical trials.

PMID- 22406269
TI  - Stat3 and Gfi-1 transcription factors control Th17 cell immunosuppressive
      activity via the regulation of ectonucleotidase expression.
AB  - Although Th17 cells are known to promote tissue inflammation and autoimmunity,
      their role during cancer progression remains elusive. Here, we showed that in
      vitro Th17 cells generated with the cytokines IL-6 and TGF-beta expressed CD39
      and CD73 ectonucleotidases, leading to adenosine release and the subsequent
      suppression of CD4(+) and CD8(+) T cell effector functions. The IL-6-mediated
      activation of the transcription factor Stat3 and the TGF-beta-driven
      downregulation of Gfi-1 transcription factor were both essential for the
      expression of ectonucleotidases during Th17 cell differentiation. Stat3 supported
      whereas Gfi-1 repressed CD39 and CD73 expression by binding to their promoters.
      Accordingly, Th17 cells differentiated with IL-1beta, IL-6, and IL-23 but without
      TGF-beta did not express ectonucleotidases and were not immunosuppressive.
      Finally, adoptive transfer of Th17 cells induced by TGF-beta and IL-6 promoted
      tumor growth in a CD39-dependent manner. Thus, ectonucleotidase expression
      supports the immunosuppressive fate of Th17 cells in cancer.

PMID- 22406270
TI  - Fluorescent in vivo detection reveals that IgE(+) B cells are restrained by an
      intrinsic cell fate predisposition.
AB  - IgE antibodies may be protective in parasite immunity, but their aberrant
      production can lead to allergic disease and life-threatening anaphylaxis. Despite
      the importance of IgE regulation, few studies have directly examined the B cells
      that express IgE, because these cells are rare and difficult to detect. Here, we
      describe fluorescent IgE reporter mice and validate a flow cytometry procedure to
      allow sensitive and specific identification of IgE-expressing B cells in vivo.
      Similar to IgG1(+) cells, IgE(+) B cells differentiated into germinal center (GC)
      B cells and plasma cells (PCs) during primary immune responses to a T cell
      dependent hapten-protein conjugate and the helminth Nippostrongylus brasiliensis.
      However, the participation of IgE(+) B cells in GCs was transient. IgE(+) B cells
      had an atypical propensity to upregulate the transcription factor Blimp-1 and
      undergo PC differentiation. Most IgE(+) PCs were short lived and showed reduced
      affinity maturation, revealing intrinsic mechanisms that restrict the IgE
      antibody response.

PMID- 22406271
TI  - Crosstalk between reverse cholesterol transport and innate immunity.
AB  - Although lipid metabolism and host defense are widely considered to be very
      divergent disciplines, compelling evidence suggests that host cell handling of
      self- and microbe-derived (e.g. lipopolysaccharide, LPS) lipids may have common
      evolutionary roots, and that they indeed may be inseparable processes. The innate
      immune response and the homeostatic network controlling cellular sterol levels
      are now known to regulate each other reciprocally, with important implications
      for several common diseases, including atherosclerosis. In the present review we
      discuss recent discoveries that provide new insight into the bidirectional
      crosstalk between reverse cholesterol transport and innate immunity, and
      highlight the broader implications of these findings for the development of
      therapeutics.

PMID- 22406272
TI  - Human parechoviruses are frequently detected in stool of healthy Finnish
      children.
AB  - BACKGROUND: Human parechoviruses (HPeVs) are common viruses mainly infecting
      young children. Most infections are mild, but HPeV3 causes severe CNS infections
      in new-born infants. OBJECTIVES: The aim was to study the epidemiology of HPeVs
      in Finnish general population in the period 1996-2007, with special emphasis on
      the different types circulating in Finland. STUDY DESIGN: A total of 2236 stool
      specimens were collected from 200 healthy Finnish children in a prospective birth
      cohort study, most before the age of 2 years. Samples were tested for the
      presence of HPeV RNA using a specific RT-PCR. The genotype of HPeV was determined
      by sequencing the VP1 genomic region. RESULTS: HPeV RNA was detected in 144
      (6.4%) specimens from 78 (39%) children. The dominant type was HPeV1 (93% of the
      type-identified 105 samples), although types 3 and 6 were also identified. HPeV
      was found sequentially in more than one sample in 43 infections lasting up to 93
      days. The positive findings were distributed equally in young ages and declined
      towards the age of 2 years. Infections clustered around the autumn months with no
      obvious change between years. No significant differences were seen between boys
      and girls. CONCLUSIONS: HPeV is a common virus infecting Finnish children under 2
      years of age. HPeVs circulate throughout the year with clear accumulation on
      autumn, also seen in individual years over the 11-year study period. The virus
      deserves increased attention and should be included in the test panel of clinical
      virus laboratories.

PMID- 22406273
TI  - Activins and inhibins in mammalian testis development: new models, new insights.
AB  - The discovery of activin and inhibins as modulators of the hypothalamic-pituitary
      gonadal axis has set the foundation for understanding their central importance to
      many facets of development and disease. This review contains an overview of the
      processes and cell types that are central to testis development and
      spermatogenesis and then provides an update focussed on information gathered over
      the past five years to address new concepts about how these proteins function to
      control testis development in fetal and juvenile life. Current knowledge about
      the interactive nature of the transforming growth factor-beta (TGFbeta)
      superfamily signalling network is applied to recent findings about activins and
      inhibins in the testis. Information about the regulated synthesis of signalling
      components and signalling regulators in the testis is integrated with new
      concepts that demonstrate their functional significance. The importance of
      activin bioactivity levels or dosage in controlling balanced growth of
      spermatogonial cells and their niche at different stages of testis development is
      highlighted.

PMID- 22406274
TI  - Roles of activin family in pancreatic development and homeostasis.
AB  - The transforming growth factor-beta (TGF-beta) superfamily of ligands have been
      recognized as important signals in vertebrate embryonic development from the
      blastula stage to adulthood. In addition to roles in early development, TGF-beta
      superfamily ligands, and particularly activin family ligands, are involved in
      specification, differentiation, and proliferation of multiple organ systems,
      including the pancreas. More recently, research has suggested that activin family
      ligands, binding proteins, receptors, and Smad signal transducers and modulators
      are involved in regulating adult pancreatic function and maintaining pancreatic
      islet homeostasis in the adult. This article will focus on outlining common
      themes in activin family regulation of embryonic pancreatic development and adult
      pancreatic homeostasis, particularly in activin family involvement in setting and
      maintaining populations of islet cells such as beta-cells.

PMID- 22406275
TI  - From macroscopic measurements to microscopic mechanisms of protein aggregation.
AB  - The ability to relate bulk experimental measurements of amyloid formation to the
      microscopic assembly processes that underlie protein aggregation is critical in
      order to achieve a quantitative understanding of this complex phenomenon. In this
      review, we focus on the insights from classical and modern theories of linear
      growth phenomena and discuss how theory allows the roles of growth and nucleation
      processes to be defined through the analysis of experimental in vitro time
      courses of amyloid formation. Moreover, we discuss the specific signatures in the
      time course of the reactions that correspond to the actions of primary and
      secondary nucleation processes, and outline strategies for identifying and
      characterising the nature of the dominant process responsible in each case for
      the generation of new aggregates. We highlight the power of a global analysis of
      experimental time courses acquired under different conditions, and discuss how
      such an analysis allows a rigorous connection to be established between the
      macroscopic measurements and the rates of the individual microscopic processes
      that underlie the phenomenon of amyloid formation.

PMID- 22406276
TI  - Scaling-up recombinant plasmid DNA for clinical trial: current concern, solution
      and status.
AB  - Gene therapy and vaccines are rapidly developing field in which recombinant
      nucleic acids are introduced in mammalian cells for enhancement, restoration,
      initiation or silencing biochemical function. Beside simplicity in manipulation
      and rapid manufacture process, plasmid DNA-based vaccines have inherent features
      that make them promising vaccine candidates in a variety of diseases. This
      present review focuses on the safety concern of the genetic elements of plasmid
      such as propagation and expression units as well as their host genome for the
      production of recombinant plasmid DNA. The highlighted issues will be beneficial
      in characterizing and manufacturing plasmid DNA for save clinical use.
      Manipulation of regulatory units of plasmid will have impact towards addressing
      the safety concerns raised in human vaccine applications. The gene revolution
      with plasmid DNA by alteration of their plasmid and production host genetics will
      be promising for safe delivery and obtaining efficient outcomes.

PMID- 22406277
TI  - Immunogenicity of one dose of Vero cell culture-derived Japanese encephalitis
      (JE) vaccine in adults previously vaccinated with mouse brain-derived JE vaccine.
AB  - BACKGROUND: There are no data on the use of inactivated Vero cell culture-derived
      Japanese encephalitis (JE) vaccine (JE-VC) as a booster among individuals who
      previously received inactivated mouse brain-derived JE vaccine (JE-MB). METHODS:
      Military personnel who received >=3 doses of JE-MB or were JE vaccine-naive were
      vaccinated with 2 doses of JE-VC on days 0 and 28. Serum neutralizing antibodies
      were measured pre-vaccination and 28 days after each dose. Non-inferiority was
      evaluated for seroprotection rate and geometric mean titer (GMT) between
      previously vaccinated participants post-dose 1 and vaccine-naive participants
      post-dose 2. RESULTS: Fifty-three previously vaccinated and 70 JE vaccine-naive
      participants were enrolled. Previously vaccinated participants had significantly
      higher GMTs pre-vaccination, post-dose 1, and post-dose 2. Seroprotection rates
      among previously vaccinated participants post-dose 1 (44/44, 100%) were
      noninferior to those achieved in previously naive participants post-dose 2
      (53/57, 93%). The GMT was significantly higher in previously vaccinated
      participants post-dose 1 (GMT 315; 95% CI 191-520) compared to previously naive
      participants post-dose 2 (GMT 79; 95% CI 54-114). CONCLUSIONS: Among military
      personnel previously vaccinated with >=3 doses of JE-MB, a single dose of JE-VC
      adequately boosts neutralizing antibody levels and provides at least short-term
      protection. Additional studies are needed to confirm these findings in other
      populations and determine the duration of protection following a single dose of
      JE-VC in prior recipients of JE-MB.

PMID- 22406278
TI  - Immunogenicity and safety of a two-dose regimen of a combined measles, mumps,
      rubella and varicella live vaccine (ProQuad((r))) in infants from 9 months of
      age.
AB  - Vaccination against measles, mumps, rubella and varicella (MMRV) is currently
      recommended in developed countries for infants from 12 months of age. However,
      measles vaccination at 9 months of age is recommended by the WHO in the Expanded
      Program on Immunization (EPI) schedule and it is therefore possible that MMR or
      MMRV vaccines might also be given at this age. This open-label, randomised,
      comparative study evaluated the immunogenicity and safety of a 2-dose schedule of
      ProQuad((r)) (MMRV vaccine) given at a 3-month interval in healthy infants aged
      >=9 months. For measles, the non-inferiority of the response rate post-Dose 2 was
      reached when Dose 1 was administered at 11 months (98%) compared with 12 months
      (99%) but was not reached when Dose 1 was administered at 9 months (95%). The
      response rate to measles post-Dose 1 increased with age, from 73% to 88% and 90%
      at 9, 11 and 12 months, respectively. For mumps, rubella and varicella, response
      rates were not different after Dose 1 (>95%) or Dose 2 (>99%) regardless of
      whether Dose 1 was administered at 9, 11 or 12 months of age. In conclusion, the
      age of administration of the first of a two-dose regimen of ProQuad may be
      lowered to 11 months. Dose 1 may be administered at 9 months if early protection
      is required, but it should be recognised that a second dose is required promptly
      with a minimum of 3-month interval between doses.

PMID- 22406279
TI  - Safety reporting in developing country vaccine clinical trials-a systematic
      review.
AB  - With more vaccines becoming available worldwide, vaccine research is on the rise
      in developing countries. To gain a better understanding of safety reporting from
      vaccine clinical research in developing countries, we conducted a systematic
      review in Medline and Embase (1989-2011) of published randomized clinical trials
      (RCTs) reporting safety outcomes with >=50% developing country participation
      (PROSPERO systematic review registration number: CRD42012002025). Developing
      country vaccine RCTs were analyzed with respect to the number of participants,
      age groups studied, inclusion of safety information, number of reported adverse
      events following immunization (AEFI), type and duration of safety follow-up, use
      of standardized AEFI case definitions, grading of AEFI severity, and the
      reporting of levels of diagnostic certainty for AEFI. The systematic search
      yielded a total number of 50 randomized vaccine clinical trials investigating 12
      different vaccines, most commonly rotavirus and malaria vaccines. In these
      trials, 94,459 AEFI were reported from 446,908 participants receiving 735,920
      vaccine doses. All 50 RCTs mentioned safety outcomes with 70% using definitions
      for at least one AEFI. The most commonly defined AEFI was fever (27), followed by
      local (16) and systemic reactions (14). Logistic regression analysis revealed a
      positive correlation between the implementation of a fever case definition and
      the reporting rate for fever as an AEFI (p=0.027). Overall, 16 different
      definitions for fever and 7 different definitions for erythema were applied.
      Predefined AEFI case definitions by the Brighton Collaboration were used in only
      two out of 50 RCTs. The search was limited to RCTs published in English or German
      and may be missing studies published locally. The reported systematic review
      suggests room for improvement with respect to the harmonization of safety
      reporting from developing country vaccine clinical trials and the implementation
      of standardized case definitions.

PMID- 22406280
TI  - Social cognition and quality of life in schizophrenia.
AB  - Schizophrenia is associated with poor quality of life (QOL). Whereas the effects
      of neurocognitive deficits and psychopathology on QOL of schizophrenia patients
      have recently been elucidated, little is known about social cognitive deficits in
      this regard. This study investigated the influence of social cognition on QOL in
      schizophrenia. A sample of 1032 patients, 1011 of their siblings, and 552 healthy
      controls was recruited from the Dutch Genetic Risk and Outcome in Psychosis
      (GROUP) study. Participants completed a battery of cognitive tests, including
      social cognitive tests on theory of mind and emotion perception. To assess QOL
      the World Health Organization QOL Assessment-BREF (WHOQOL-BREF) was used.
      Schizophrenia symptoms were assessed with the Positive and Negative Syndrome
      Scale (PANSS). Social cognitive performance was significantly worse in patients
      compared to siblings and healthy controls. Patients had the poorest QOL, while
      QOL in healthy controls was better than in siblings. Theory of mind but not
      emotion perception or neurocognition was associated with QOL in patients, whereas
      neurocognition was the only significant predictor of QOL in siblings and healthy
      controls. There was a significant interaction between theory of mind and symptom
      severity with respect to QOL. Our study indicates that social cognition is
      associated with QOL in schizophrenia. Theory of mind rather than emotion
      perception is associated with QOL, and this association is moderated by
      schizophrenia symptoms. In particular, patients with relatively unimpaired theory
      of mind and more severe schizophrenia symptoms have poor QOL and could therefore
      benefit from therapeutic intervention.

PMID- 22406281
TI  - Theory of mind in patients with schizophrenia: is mentalizing delayed?
AB  - OBJECTIVE: Functional imaging studies have used numerous neurocognitive designs
      to investigate brain activation during theory of mind (ToM) tasks in patients
      with schizophrenia. The majority of studies asks participants to retrospectively
      attribute mental states to others. We used a novel animated task to investigate
      implicit mentalizing online. Because behavioral studies have revealed slower ToM
      performance reaction times in patients with schizophrenia, we hypothesized that
      time would influence functional MRI (fMRI) activation patterns also. METHODS: We
      applied the "Moving Shapes" paradigm, which involves two interacting triangles,
      to a functional MRI block design and investigated the neural activation patterns
      of 15 patients with schizophrenia and 14 healthy controls. We additionally
      analyzed the first and second halves of each video separately to assess time
      related differences. RESULTS: Overall, patients with schizophrenia showed
      increased activation in the inferior and middle frontal gyri, the superior
      temporal gyrus, the precuneus and the cerebellum compared with controls during
      ToM versus non-ToM videos. Most importantly, patients with schizophrenia had
      predominantly increased activation in ToM-related brain areas during the second
      half of the ToM paradigm, whereas the activation in areas of the ToM-network in
      healthy controls occurred during the first half of the presentation. CONCLUSIONS:
      Our results confirm recent findings of significantly stronger neural activations
      that encompass the fronto-temporo-parietal cerebral areas in patients with
      schizophrenia compared with controls during ToM tasks. The observation of slower
      cognitive processing in patients with schizophrenia during mentalizing might
      explain some of the contradictory imaging findings in these patients and have
      implications for cognitive remediation.

PMID- 22406282
TI  - Comparative structural analysis of eukaryotic flagella and cilia from
      Chlamydomonas, Tetrahymena, and sea urchins.
AB  - Although eukaryotic flagella and cilia all share the basic 9+2 microtubule
      organization of their internal axonemes, and are capable of generating bending
      motion, the waveforms, amplitudes, and velocities of the bending-motions are
      quite diverse. To explore the structural basis of this functional diversity of
      flagella and cilia, we here compare the axonemal structure of three different
      organisms with widely divergent bending-motions by electron cryo-tomography. We
      reconstruct the 3D structure of the axoneme of Tetrahymena cilia, and compare it
      with the axoneme of the flagellum of sea urchin sperm, as well as with the
      axoneme of Chlamydomonas flagella, which we analyzed previously. This comparative
      structural analysis defines the diversity of molecular architectures in these
      organisms, and forms the basis for future correlation with their different
      bending-motions.

PMID- 22406283
TI  - Regional analysis of the effect of paved roads on sodium and chloride in lakes.
AB  - Salinization of surface water from sodium chloride (road salt) applied to paved
      roads is a widely recognized environmental concern in the northern hemisphere,
      yet practical information to improve winter road management to reduce the
      environmental impacts of this deicer is lacking. The purpose of our study was to
      provide such information by developing baseline concentrations for sodium and
      chloride for lakes in watersheds without paved roads, and then determining the
      relationship between these ions and density, type, and proximity of paved roads
      to shoreline. We used average summer (June-September) sodium and chloride data
      for 138 lakes combined in a watershed based analysis of paved road networks in
      the Adirondack Park of New York, U.S.A. The watersheds used in our study
      represented a broad range in paved road density and type, 56 of which had no
      paved roads. Median lake sodium and chloride concentrations in these 56
      watersheds averaged 0.55 and 0.24 mg/L, respectively. In contrast, the median
      sodium and chloride concentrations for the 82 lakes in watersheds with paved
      roads were 3.60 and 7.22 mg/L, respectively. Paved road density (lane-km/km(2))
      was positively correlated with sodium and chloride concentrations, but only state
      roads were significantly correlated with sodium and chloride while local roads
      were not. State road density alone explained 84 percent of the variation in both
      ions. We also successfully modeled the relationship between road proximity to
      shoreline and sodium and chloride concentrations in lakes, which allowed us to
      identify sections of road that contributed more to explaining the variation in
      sodium and chloride in lakes. This model and our approach could be used as part
      of larger efforts to identify environmentally sensitive areas where alternative
      winter road management treatments should be applied.

PMID- 22406284
TI  - Ammonium recovery and energy production from urine by a microbial fuel cell.
AB  - Nitrogen recovery through NH(3) stripping is energy intensive and requires large
      amounts of chemicals. Therefore, a microbial fuel cell was developed to
      simultaneously produce energy and recover ammonium. The applied microbial fuel
      cell used a gas diffusion cathode. The ammonium transport to the cathode occurred
      due to migration of ammonium and diffusion of ammonia. In the cathode chamber
      ionic ammonium was converted to volatile ammonia due to the high pH. Ammonia was
      recovered from the liquid-gas boundary via volatilization and subsequent
      absorption into an acid solution. An ammonium recovery rate of 3.29 g(N) d(-1) m(
      2) (vs. membrane surface area) was achieved at a current density of 0.50 A m(-2)
      (vs. membrane surface area). The energy balance showed a surplus of energy 3.46
      kJ g(N)(-1), which means more energy was produced than needed for the ammonium
      recovery. Hence, ammonium recovery and simultaneous energy production from urine
      was proven possible by this novel approach.

PMID- 22406285
TI  - Rapid effects of diverse toxic water pollutants on chlorophyll a fluorescence:
      variable responses among freshwater microalgae.
AB  - Chlorophyll a fluorescence of microalgae is a compelling indicator of toxicity of
      dissolved water contaminants, because it is easily measured and responds rapidly.
      While different chl a fluorescence parameters have been examined, most studies
      have focused on single species and/or a narrow range of toxins. We assessed the
      utility of one chl a fluorescence parameter, the maximum quantum yield of PSII
      (F(v)/F(m)), for detecting effects of nine environmental pollutants from a range
      of toxin classes on 5 commonly found freshwater algal species, as well as the
      USEPA model species, Pseudokirchneriella subcapitata. F(v)/F(m) declined rapidly
      over <20 min in response to low concentrations of photosynthesis-specific
      herbicides Diuron((r)) and metribuzin (both <40 nM), atrazine (<460 nM) and
      terbuthylazine (<400 nM). However, F(v)/F(m) also responded rapidly and in a dose
      dependent way to toxins glyphosate (<90 MUM), and KCN (<1 mM) which have modes of
      action not specific to photosynthesis. F(v)/F(m) was insensitive to 30-40 MUM
      insecticides methyl parathion, carbofuran and malathion. Algal species varied in
      their sensitivity to toxins. No single species was the most sensitive to all nine
      toxins, but for six toxins to which algal F(v)/F(m) responded significantly, the
      model species P. subcapitata was less sensitive than other taxa. In terms of
      suppression of F(v)/F(m) within 80 min, patterns of concentration-dependence
      differed among toxins; most showed Michaelis-Menten saturation kinetics, with
      half-saturation constant (K(m)) values for the PSII inhibitors ranging from 0.14
      MUM for Diuron((r)) to 6.6 MUM for terbuthylazine, compared with a K(m) of 330
      MUM for KCN. Percent suppression of F(v)/F(m) by glyphosate increased
      exponentially with concentration. F(v)/F(m) provides a sensitive and easily
      measured parameter for rapid and cost-effective detection of effects of many
      dissolved toxins. Field-portable fluorometers will facilitate field testing,
      however distinct responses between different species may complicate net F(v)/F(m)
      signal from a community.

PMID- 22406286
TI  - Doping of biogenic Pd catalysts with Au enables dechlorination of diclofenac at
      environmental conditions.
AB  - By using the metal reducing capacities of bacteria, Pd nanoparticles can be
      produced in a sustainable way ('bio-Pd'). These bio-Pd nanoparticles can be used
      as a catalyst in, for example, dehalogenation reactions. However, some
      halogenated compounds are not efficiently degraded using a bio-Pd catalyst. This
      study shows that the activity of bio-Pd can be improved by doping with Au(0)
      ('bio-Pd/Au'). In contrast with bio-Pd, bio-Pd/Au could perform the removal of
      the model pharmaceutical compound diclofenac from an aqueous medium in batch
      experiments at neutral pH and with H(2) as the hydrogen donor (first order decay
      constant of 0.078 +/- 0.009 h(-1)). Dehalogenation was for both catalysts the
      only observed reaction. For bio-Pd/Au, a disproportional increase of catalytic
      activity was observed with increasing Pd-content of the catalyst. In contrast,
      when varying the Au-content of the catalyst, a Pd/Au mass ratio of 50/1 showed
      the highest catalytic activity (first order decay value of 0.52 +/- 0.02 h(-1)).
      The removal of 6.40 MUg L(-1) diclofenac from a wastewater treatment plant
      effluent using bio-Pd was not possible even after prolonged reaction time.
      However, by using the most active bio-Pd/Au catalyst, 43.8 +/- 0.5% of the
      initially present diclofenac could be removed after 24 h. This study shows that
      doping of bio-Pd nanoparticles with Au(0) can be a promising approach for the
      reductive treatment of wastewaters containing halogenated contaminants.

PMID- 22406287
TI  - Interaction energy evaluation of soluble microbial products (SMP) on different
      membrane surfaces: role of the reconstructed membrane topology.
AB  - Soluble microbial products (SMP), a majority of organic matter in effluents, play
      a key role in membrane fouling. A series of filtration experiments were
      conducted, and demonstrated that the flux decrement rate was in order of
      cellulose acetate membrane (CA, 65.4%), polyvinylidene fluoride (PVDF, 47.9%) and
      polyether sulfones (PES, 29.2%). Results showed that the fouling behavior of
      membrane should be predicted from the combined knowledge of solution chemistry,
      surface chemical properties and surface morphology. To better understand the
      interactions between the SMP and different membranes, a technique for
      reconstructing the membrane surface topology was developed on the basis of
      statistical parameters obtained from atomic force microscopy. The interaction
      energy, represented by extended Derjaguin-Landau-Verwey-Overbeek (XDLVO)
      potential, was calculated by surface element integration, allowing exploring the
      interaction energy profiles for different surfaces and providing considerable
      insights into the role of such interactions on the macroscopic fouling behavior.
      The resulting interaction energy differed considerably from the corresponding
      interaction between perfectly smooth surfaces. The great influence of protrusion
      on the membrane surface was to reduce the primary energy barrier height, thus
      rendering rough surface more favorable for deposition. An attractive energy
      region was immediately surrounded by each positive asperity as demonstrated in
      the roughness-engendered interaction energy maps. As the SMP approached closer to
      the membrane, they had a high probability of getting trapped in the attractive
      energy region, leading to a more rapid loss of flux than smooth membrane.

PMID- 22406288
TI  - Occurrence and antibiotic resistance of multiple Salmonella serotypes recovered
      from water, sediment and soil on mid-Atlantic tomato farms.
AB  - Salmonella outbreaks associated with the consumption of raw tomatoes have been
      prevalent in recent years. However, sources of Salmonella contamination of
      tomatoes remain poorly understood. The objectives of this study were to identify
      ecological reservoirs of Salmonella on tomato farms, and to test antimicrobial
      susceptibilities of recovered Salmonella isolates. Fourteen Mid-Atlantic tomato
      farms in the U.S. were sampled in 2009 and 2010. Groundwater, irrigation pond
      water, pond sediment, irrigation ditch water, rhizosphere and irrigation ditch
      soil, leaves, tomatoes, and swabs of harvest bins and worker sanitary facilities
      were analyzed for Salmonella using standard culture methods and/or a flow-through
      immunocapture method. All presumptive Salmonella isolates (n=63) were confirmed
      using PCR and the Vitek((r)) 2 Compact System, and serotyped using the
      Premi((r))Test Salmonella and a conventional serotyping method. Antimicrobial
      susceptibility testing was carried out using the SensititreTM microbroth dilution
      system. Four of the 14 farms (29%) and 12 out of 1,091 samples (1.1%) were found
      to harbor Salmonella enterica subsp. enterica. Salmonella was isolated by the
      immunocapture method from soil, while the culture method recovered isolates from
      irrigation pond water and sediment, and irrigation ditch water. No Salmonella was
      detected on leaves or tomatoes. Multiple serotypes were identified from soil and
      water, four of which-S. Braenderup, S. Javiana, S. Newport and S. Typhimurium
      have been previously implicated in Salmonella outbreaks associated with tomato
      consumption. Resistance to sulfisoxazole was prevalent and some resistance to
      ampicillin, cefoxitin, amoxicillin/clavulanic acid, and tetracycline was also
      observed. This study implicates irrigation water and soil as possible reservoirs
      of Salmonella on tomato farms and irrigation ditches as ephemeral habitats for
      Salmonella. The findings point to the potential for pre-harvest contamination of
      tomatoes from contaminated irrigation water or from soil or water splash from
      irrigation ditches onto low-lying portions of tomato plants.

PMID- 22406289
TI  - Mercury speciation in brain tissue of polar bears (Ursus maritimus) from the
      Canadian Arctic.
AB  - Methylmercury (MeHg) is a neurotoxicant that has been found at elevated
      concentrations in the Arctic ecosystem. Little is known about its internal dose
      in wildlife such as polar bears. We measured concentrations of mercury (Hg) in
      three different brain regions (cerebellum, frontal lobe and brain stem) of 24
      polar bears collected from the Nunavik, Canada between 2000 and 2003. Speciation
      of Hg was measured by High Performance Liquid Chromatography coupled to
      Inductively Coupled Plasma Mass Spectroscopy (HPLC-ICP-MS). Concentrations of
      mean total Hg in brain tissue were up to 625 times lower (0.28 +/- 0.07 mg kg(-1)
      dry weight (dw) in frontal lobe, 0.23 +/- 0.07 mg kg(-1) dw in cerebellum and
      0.12 +/- 0.0 3mg kg(-1) dw in brain stem) than the mean total Hg concentration
      previously reported in polar bear liver collected from Eastern Baffin Island.
      Methylmercury (MeHg) accounted for 100% of the Hg found in all three brain
      regions analyzed. These results suggest that polar bear might reduce the toxic
      effects of Hg by limiting the uptake into the brain and/or decrease the rate of
      demethylation so that Hg can be excreted from the brain more easily. The
      toxicokinetics and the blood-brain-barrier mechanisms of polar bears are still
      unknown and further research is required.

PMID- 22406290
TI  - Trunk muscle control in response to (un)expected turns in cart pushing.
AB  - Before altering the travel direction in normal gait, anticipatory activation in
      trunk muscles is observed, followed by a top-down sequence of rotation of body
      segments. Turning while pushing a cart is a more challenging task for the trunk
      because of its low stiffness in pushing while walking and the interaction with
      the high inertia of the cart. 12 healthy subjects pushed a 200 kg cart at
      shoulder and hip height while making turns (gradual, sharp and unexpected sharp).
      The normalized electromyogram amplitudes of left (right) lateral and anterior
      external oblique muscle, and right (left) internal oblique muscle were averaged
      to represent left (right) trunk rotator muscle activity. The baseline values of
      trunk rotator muscle activity before the turn and the peak values after the turn
      were determined. Additionally, peak values of hand forces, twisting moments and
      twisting motions were assessed. Before turning, higher trunk rotator muscle
      activity than in straight pushing without turning was only observed before making
      a turn in the gradual or sharp turn conditions. After the turn, clockwise
      twisting motion was associated with a clockwise twisting moment induced by the
      reaction forces at the left hand. Anticipatory activation was initially absent in
      the unexpected sharp turn, while bilateral trunk rotator muscle activity
      increased after the turn, indicating co-contraction. In the unexpected turn
      condition the combination of an uncontrolled twisting motion with delayed muscle
      activation may increase the potential risk of low-back injury.

PMID- 22406292
TI  - Gait speed is a responsive measure of physical performance for patients
      undergoing short-term rehabilitation.
AB  - Based on its ability to predict consequential outcomes, gait speed has been
      recommended as a "vital sign" for older individuals. Recommendations
      notwithstanding, the value of comfortable gait speed as a measure is limited
      unless clinicians can use it to identify real changes in performance over time.
      The purpose of this study, therefore, was to broadly describe the responsiveness
      of comfortable gait speed measured from patients admitted to short-term
      rehabilitation. For 136 consecutive patients who met inclusion and exclusion
      criteria (mean age=73.6 years), information regarding assistance, device use, and
      speed was obtained. Speed was measured as patients walked at a comfortable speed
      over 5.2m. The admission gait speed was a mean (SD) .40 (.18)m/s. The discharge
      speed was .59 (.20)m/s. The change in speed from admission to discharge (mean
      15.1 days) was .20 (.16)m/s. The minimal detectable change (95%) was .13 m/s. The
      effect size was 1.11; the standardized response mean was 1.25. Based on receiver
      operating characteristic curve analysis, the minimal clinically important
      difference associated with 4 anchors (1 - subjective change in overall walking, 2
      - change in assistance required, 3 - change in assistive device used, and 4 -
      change in speed based classification) ranged from .10 to .18 m/s. On the basis of
      multiple distribution- and anchor-based indicators, comfortable gait speed can be
      considered a responsive measure for patients undergoing short-term
      rehabilitation.

PMID- 22406291
TI  - Effects of biofeedback on secondary-task response time and postural stability in
      older adults.
AB  - Real-time single- and multiple-axis vibrotactile feedback of trunk motion has
      been shown to significantly decrease mean trunk tilt and decrease time spent
      outside a no vibrotactile feedback zone (dead zone) in older adults within a
      laboratory setting. This study aimed to determine if these improvements can
      translate into everyday use, during which other tasks may simultaneously demand
      attention. A dual-task paradigm was used in which 10 community-dwelling older
      adults were asked to perform standing trials in the presence of a secondary task
      (verbal or push-button), vibrotactile feedback, or both (dual-task). Results show
      that subjects significantly increased the percentage of time inside the dead zone
      when feedback was provided compared to when it was not during both verbal
      (+13.6%) and push-button (+10.1%) secondary tasks. Providing feedback also
      decreased RMS of trunk tilt during both secondary tasks (verbal: -0.129 degrees ;
      push-button: -0.138 degrees ). However, response times for secondary tasks
      increased (verbal: +119 ms; push-button: +110 ms) when feedback was provided.
      These results suggest that while vibrotactile feedback does increase attentional
      load in older adults, it can still be used effectively to improve postural
      metrics in high cognitive load situations.

PMID- 22406293
TI  - Functional niche of inflamed synovium for Th17-cell expansion and activation in
      rheumatoid arthritis: implication to clinical therapeutics.
AB  - Th17 cells selectively produce the signature cytokines such as IL-17, IL-21 and
      IL-22, and play a critical role for the chronic inflammatory response and
      subsequent tissue damage in synovial joints of patients with rheumatoid arthritis
      (RA). The preliminary clinical study indicates that IL-17 neutralizing therapy
      can ameliorate inflammatory cascades within peripheral synovial joints in the
      major population of patients with active RA. Multiple cellular and molecular
      modulations for the Th17-cell-polarized responses could exist, however, in the
      inflamed synovium, possibly resulting in a functional niche for the generation
      and activation of pathogenic Th17 cells. This might establish a vicious cycle
      culminating in the striking marginal erosions of cartilage and bone in the RA
      joints, and at least partially abrogate the potential therapeutic benefits
      related to IL-17 antagonizing or Th17-cell depleting therapy. This article is
      aimed to discuss the cellular and molecular pathways critically involved in the
      expansion and activation of pathogenic Th17 cells in RA synovium, with emphasis
      on the potential therapeutic implications for targeting these pathways to the
      present and future RA clinics.

PMID- 22406294
TI  - Impact of probe compound in MRP2 vesicular transport assays.
AB  - MRP2 is an efflux transporter that is expressed mainly in the canalicular
      membrane of hepatocytes, where it expels polar and ionic compounds into the bile.
      MRP2 is also present in the apical membrane of enterocytes and epithelial cells
      of proximal tubules of the kidney. Inhibition of MRP2 transport can lead to the
      accumulation of metabolites and other MRP2 substrates up to toxic levels in these
      cells. The transport properties of MRP2 are frequently studied with the vesicular
      transport assay. The assay identifies compounds that interact with MRP2 by
      measuring the effect of a compound on the transport of a radioactively labeled or
      fluorescent probe. We have compared the effect of eight selected test compounds
      (quercetin, disopyramide, paracetamol, indomethacin, diclofenac, estrone-3
      sulfate, budesonide, and thioridazine) on the MRP2-mediated transport of three
      commonly used probes: 5(6)-carboxy-2,7-dichlorofluorescein, leukotriene C4 and
      estradiol-17-beta-d-glucuronide (E217betaG). Five of the test compounds had
      different probe-dependent effects on the MRP2-mediated transport, suggesting
      differences in the transport mechanism of the probes. Our results underline the
      complexity of substrate recognition by these efflux transporters and the
      difficulties in directly comparing results obtained with different assays,
      especially when different probes are used.

PMID- 22406295
TI  - Supramolecular effects on the antifungal activity of cyclodextrin/di-n
      decyldimethylammonium chloride mixtures.
AB  - Candidiasis infections are growing problem worldwide especially for the
      immunocompromised individuals. Di-n-decyldimethylammonium chloride is one of the
      most common antifungal agents used to clean medical devices. The current study
      examines the antifungal mechanism of di-n-decyldimethylammonium cation and its
      cyclodextrin inclusion complexes. Depending on the type of cyclodextrin (alpha-,
      beta- or gamma-CD), inclusion complexes can be as active as ammonium alone in
      terms of microorganism death (fungicidal activity). Moreover, with beta-CD
      inclusion complexes, synergism is observed against fungus growth (fungistatic
      activity). Based on molecular dynamics, we propose a mechanism supported by cell
      number, selective electrode and zeta-potential measurements as a function of
      time. The mechanism involves four steps: (i) the positively-charged complex
      diffuses through the solution, (ii) it adsorbs onto the fungus membrane surface
      by electrostatic interaction, (iii) then it dissociates and the ammonium inserts
      in the microorganism membrane, and (iv) the change of the cell surface charge
      induces cell lysis.

PMID- 22406296
TI  - High resolution melt analysis to track infections due to ribotype 027 Clostridium
      difficile.
AB  - The increased prevalence of hypervirulent ribotype 027 Clostridium difficile
      requires rapid identification of isolates in order to implement timely infection
      control strategies. High resolution melt (HRM) analysis of PCR products can
      identify strain variation amongst genera of bacteria. The intergenic (16S-23S
      rDNA) spacer region contains sequence regions conserved within genera and other
      sequence region variables between species within genera. We wished to investigate
      whether HRM analysis of PCR ribotyping products could identify ribotype 027 C.
      difficile. Ribotyping was performed on 93 clinical isolates and five control
      strains and band patterns were analysed using GelCompar II (Applied Maths, USA).
      Real-time PCR using ribotyping primers was performed and normalised melt curves
      were generated. The HRM data was then imported into ScreenClust software (QIAGEN)
      to generate principal component analysis graphs depicting clustered relationships
      of strains. Ribotyping produced clear PCR bands for 88/98 isolates tested.
      Dendrograms generated by GelCompar showed a diversity of ribotype patterns
      amongst these 88 isolates with 18 groups identified with 70% homology. One
      clinical isolate showed 100% homology with the control 027 strains. ScreenClust
      analysis of the same 88 HRM results showed clustering of isolates, with 027
      strains identifiable as a unique cluster. HRM analysis correctly identified the
      control 027 stains and the clinical isolate shown to be 027. HRM combined with
      ScreenClust analysis of real-time PCR products of the 16S-23S rDNA spacer region
      successfully identified ribotype 027 strains. For infection control purposes this
      was achieved within 2-3 h of colony isolation.

PMID- 22406297
TI  - IQGAP2, A candidate tumour suppressor of prostate tumorigenesis.
AB  - Loss of IQGAP2 contributes to the tumorigenesis of hepatocellular carcinoma and
      gastric cancer. However, whether IQGAP2 also suppresses prostate tumorigenesis
      remains unclear. We report here that IQGAP2 is a candidate tumour suppressor of
      prostate cancer (PC). Elevated IQGAP2 was detected in prostatic intraepithelial
      neoplasia (PIN), early stages of PCs (Gleason score <=3), and androgen-dependent
      LNCaP PC cells. However, IQGAP2 was expressed at substantially reduced levels not
      only in prostate glands and non-tumorigenic BPH-1 prostate epithelial cells but
      also in advanced (Gleason score 4 or 5) and androgen-independent PCs.
      Furthermore, xenograft tumours that were derived from stem-like DU145 cells
      displayed advanced features and lower levels of IQGAP2 in comparison to xenograft
      tumours that were produced from non stem-like DU145 cells. Collectively, these
      results suggest that IQGAP2 functions in the surveillance of prostate
      tumorigenesis. Consistent with this concept, ectopic IQGAP2 reduced the
      proliferation of DU145, PC3, and 293T cells as well as the invasion ability of
      DU145 cells. While ectopic IQGAP2 up-regulated E-cadherin in DU145 and PC3 cells,
      knockdown of IQGAP2 reduced E-cadherin expression. In primary PC and DU145 cells
      derived xenograft tumours, the majority of tumours with high levels of IQGAP2
      were strongly-positive for E-cadherin. Therefore, IQGAP2 may suppress PC
      tumorigenesis, at least in part, by up-regulation of E-cadherin. Mechanistically,
      overexpression of IQGAP2 significantly reduced AKT activation in DU145 cells and
      inhibition of AKT activation upregulated E-cadherin, suggesting that IQGAP2
      increases E-cadherin expression by inhibiting AKT activation. Taken together, we
      demonstrate here that IQGAP2 is a candidate tumour suppressor of PC.

PMID- 22406299
TI  - IPG-strips versus off-gel fractionation: advantages and limits of two-dimensional
      PAGE in separation of microsomal fractions of frequently used plant species and
      tissues.
AB  - The crucial cellular role of membrane proteins is generally known for all life
      forms. Depending on the species, tissue, compartment, function and physiological
      condition, membranes differ in their protein and lipid profiles. Additionally,
      occurrence of microdomains hampers quantitative protein solubilisation and
      therefore membrane proteomics remain a major challenge. In the present study
      sample preparation (TCA/acetone and methanol/chloroform precipitation with and
      without SDS pre-solubilisation) for two-dimensional PAGE were compared for
      microsomal fractions of leaves (Arabidopsis thaliana, Nicotiana tabaccum, Pisum
      sativum) and roots (P. sativum, Zea mays). Generally, pre-solubilisation with SDS
      impaired the resolution of the gels. All samples showed higher spot yields with
      TCA/acetone precipitation. Finally, we compared the results of conventional 2D
      PAGE (IPG/SDS-PAGE) and the combination of off-gel fractionation in the first
      dimension, 10% urea-SDS-PAGE in the second-dimension. Results showed that more
      spots are present in the alkaline pH range after off-gel fractionation then on
      conventional 2D-PAGE. For the first time, off-gel fractionation was combined with
      SDS/SDS-PAGE and BAC/SDS-PAGE to improve the resolution after off-gel
      fractionation. Transmembrane domains and GRAVY were calculated for all
      significantly identified spots resulting from the MALDI-TOF-TOF mass spectrometry
      showing that in the second dimension after off-gel fractionation 10.3% more
      transmembrane proteins were identified compared to IPG/SDS-PAGE.

PMID- 22406298
TI  - Differences in gait pattern parameters between medial and anterior knee pain in
      patients with osteoarthritis of the knee.
AB  - BACKGROUND: Patients with osteoarthritis of the knee have unique spatiotemporal
      gait alterations. These gait changes have not yet been differentiated according
      to the location of knee pain. The purpose of this study was to compare the gait
      patterns of patients with symptomatic knee osteoarthritis that exhibit either
      anterior or medial joint pain. METHODS: 240 Patients with knee osteoarthritis
      were evaluated at one therapy center. Patients were divided into two groups
      according to the location of greatest pain in their worse knee. Patients
      underwent a computerized spatiotemporal gait analysis. Differences in gait
      patterns between the two knee pain locations were also examined within each
      gender. FINDINGS: Compared with patients with pain in the anterior knee
      compartment, those with pain in the medial knee compartment exhibited a
      significantly slower walking speed (P<0.01), shorter step length (P<0.01), lower
      single-limb-support phase (P<0.01). These differences are witnessed mainly
      between the females in each group, whereas males differed only in single-limb
      support. INTERPRETATION: The results of this study suggested underlying gait
      differences in the nature of medial and anterior knee pain. Furthermore, gender
      differences in gait may exist between patients with medial knee pain compared to
      patients with anterior knee pain.

PMID- 22406300
TI  - Endothelin-1 and -2: two amino acids matter.
AB  - AIMS: Endothelin-1 (ET-1) and endothelin-2 (ET-2; Trp(6)Leu(7)ET-1) are expressed
      by different cell types, but are considered to display identical pharmacological
      properties on endothelin receptors. We studied agonist-dependent aspects of
      endothelin(A) (ET(A))-receptor function and the importance of amino acids 6 and 7
      of ET-1 and ET-2 in this respect. MAIN METHODS: We used isolated rat mesenteric
      resistance arteries in wire myographs, in a setting that minimizes influences of
      endothelium and sensorimotor nerves, to study arterial smooth muscle ET(A)
      receptor-mediated vasomotor responses, to ET-1, ET-2 and chimeras thereof
      (Trp(6)ET-1 and Leu(7)ET-1). KEY FINDINGS: ET-1 and ET-2 cause arterial
      contractions with comparable sensitivities and maximal responses. BQ123 (ET(A)
      antagonist) reduces sensitivity to ET-1 more potently than that to ET-2 (pK(B):
      7.1 +/- 0.2 versus 5.6 +/- 0.4). However, 1 MUM BQ123 relaxes maximal contractile
      responses to ET-2 more markedly than those to ET-1. Leu(7)ET-1 is a contractile
      agonist with lower potency and similar maximal effect compared to ET-1 and
      greater sensitivity to BQ123 than ET-2. Up to 256 nM Trp(6)ET-1 did not cause
      contraction and did not antagonize arterial responses to ET-1. SIGNIFICANCE:
      Arterial smooth muscle ET(A)-receptor function displays agonist-dependent
      aspects. This involves roles of amino acids on position 6 and 7 of the endothelin
      sequence. Agonist-dependent pathologies may benefit from the design of specific,
      agonist-selective ET-receptor antagonists.

PMID- 22406301
TI  - Chronic inhibition of nuclear factor kappa B attenuates aldosterone/salt-induced
      renal injury.
AB  - AIMS: Recent studies suggested that nuclear factor kappa B (NF-kappaB) plays a
      key role in the pathogenesis of renal injury. This study investigated whether NF
      kappaB inhibition attenuates progressive renal damage in aldosterone/salt-induced
      renal injury and its mechanisms. MAIN METHODS: Adult male rats were
      uninephrectomized and treated with one of the following for 4 weeks: vehicle
      (0.5% ethanol, subcutaneously); vehicle/1% NaCl (1% NaCl in drinking solution);
      aldosterone/1% NaCl (1% NaCl in drinking solution and aldosterone, 0.75 MUg/h,
      subcutaneously); or aldosterone/1%NaCl+pyrrolidine dithiocarbamate (PDTC), an
      inhibitor of NF-kappaB (100 mg/kg/day, by gavage). The activity of NF-kappaB was
      measured by EMSA and immunohistochemistry, CTGF and ICAM-1 were measured by
      Western blot and real-time PCR, and TGF-beta and CTGF were measured by
      immunohistochemistry. KEY FINDINGS: Rats that received aldosterone/1% NaCl
      exhibited hypertension and severe renal injury. Renal cortical mRNA levels of
      CTGF, TGF-beta, ICAM-1 and collagen IV, protein expression of CTGF and ICAM-1,
      and NF-kappaB-DNA binding activity were significantly upregulated in rats that
      received aldosterone/1% NaCl. Treatment with PDTC significantly decreased the
      percentage of cells positive for CTGF and TGF-beta; mRNA levels of CTGF, TGF
      beta, ICAM-1 and collagen IV, and protein levels of CTGF and ICAM-1 were also
      inhibited by PDTC. SIGNIFICANCE: These data suggest that the NF-kappaB signal
      pathway plays a role in the progression of aldosterone/salt-induced renal injury.

PMID- 22406302
TI  - Regulation of airway inflammation and remodeling by muscarinic receptors:
      perspectives on anticholinergic therapy in asthma and COPD.
AB  - Acetylcholine is the primary parasympathetic neurotransmitter in the airways and
      an autocrine/paracrine secreted hormone from non-neuronal origins including
      inflammatory cells and airway structural cells. In addition to the well-known
      functions of acetylcholine in regulating bronchoconstriction and mucus secretion,
      it is increasingly evident that acetylcholine regulates inflammatory cell
      chemotaxis and activation, and also participates in signaling events leading to
      chronic airway wall remodeling that is associated with chronic obstructive airway
      diseases including asthma and COPD. As muscarinic receptors appear responsible
      for most of the pro-inflammatory and remodeling effects of acetylcholine, these
      findings have significant implications for anticholinergic therapy in asthma and
      COPD, which is selective for muscarinic receptors. Here, the regulatory role of
      acetylcholine in inflammation and remodeling in asthma and COPD will be discussed
      including the perspectives that these findings offer for anticholinergic therapy
      in these diseases.

PMID- 22406303
TI  - Left main coronary stenting in a non surgical octogenarian population: a possible
      approach.
AB  - Coronary artery bypass grafting is conventionally considered the standard
      treatment for significant left main coronary artery (LMCA) disease. The
      management of LMCA disease in octogenarians is however still debated. The aim of
      this study was to appreciate the safety and effectiveness of percutaneous
      coronary intervention (PCI) for LMCA disease in octogenarians who were denied for
      surgical revascularization. The study included 70 consecutive patients >=80 years
      of age who had undergone PCI for the treatment of LMCA and who were primary
      denied by our center's heart team for surgical revascularization. Mean age was
      83.4+/-2.6 years. Mean Euroscore was 21.1+/-16.7 and mean Syntax score was 28.6+/
      8.7. Overall in-hospital mortality was 11%. Mean follow-up time was 30.5+/-24.2
      months. Overall mortality at the end of follow-up was 28%. Cardiac death was
      found in 18 patients and 2 patients died from terminal renal insufficiency. One
      patient (2%) presented with a new STEMI, 7 (11.3%) with a new non-STEMI, 13 (21%)
      with heart failure, and 2 (3.2%) had minor hemorrhage. There was a percutaneous
      target vessel revascularization in 6 (10%) patients. During follow-up, the total
      major adverse cerebral and cardiovascular event (MACCE including death, non-fatal
      acute myocardial infarction (AMI), target lesion revascularization (TLR), or
      stroke) was 27.4%. Stent implantation was relatively safely applied for the
      treatment of LMCA disease in octogenarians who were refused for surgery and who
      represented a high risk population. Despite a non-negligible rate of MACCE, the
      clinical long term outcome seems correct for this specific population with heavy
      basal status.

PMID- 22406304
TI  - Successful removal of an entrapped and kinked catheter during right transradial
      cardiac catheterization by snaring and unwinding the catheter via femoral access.
AB  - Since its introduction by Campeau in 1989, the transradial approach for coronary
      angiography has gained significant popularity among interventional cardiologists
      due to its lower access site complication rates, cost-effectiveness, and shorter
      hospital course. Although the transradial approach is much safer than the
      transfemoral approach, it has its own inherent rare complications including
      radial artery occlusion, thrombosis, nonocclusive radial artery injury,
      vasospasm, and compartment syndrome. Herein, we present an unusual case of
      entrapment and kinking of a catheter in the radial artery, which was successfully
      removed by using a gooseneck snare via the transfemoral route. The distal and
      proximal tips were then simultaneously rotated in opposite directions, allowing
      for the unkinking and removal of the catheter. To our knowledge, this is the
      first report of this rare complication.

PMID- 22406305
TI  - Sleep duration across the lifespan: implications for health.

PMID- 22406306
TI  - Nitric oxide in the regulation of the sleep-wake states.
AB  - Nitric oxide (NO) production involves four different NO-synthases (NOSs) that are
      either constitutive (neuronal, nNOS; endothelial, eNOS; mitochondrial, mNOS) or
      inducible (iNOS) in nature. Three main processes regulate NO/NOSs output, i.e.,
      the L-arginine/arginase substrate-competing system, the L
      citrulline/arginosuccinate-recycling system and the asymmetric dimethyl
      /monomethyl-L-arginine-inhibiting system. In adult animals, nNOS exhibits a dense
      innervation intermingled with pontine sleep structures. It is well established
      that the NO/nNOS production makes a key contribution to daily homeostatic sleep
      (slow-wave sleep, SWS; rapid eye movement sleep, REM sleep). In the basal
      hypothalamus, the NO/nNOS production further contributes to the REM sleep rebound
      that takes place after a sleep deprivation (SD). This production may also
      contribute to the sleep rebound that is associated with an immobilization stress
      (IS). In adult animals, throughout the SD time-course, an additional NO/iNOS
      production takes place in neurons. Such production mediates a transitory SD
      related SWS rebound. A transitory NO/iNOS production is also part of the immune
      system. Such a production contributes to the SWS increase that accompanies
      inflammatory events and is ensured by microglial cells and astrocytes. Finally,
      with aging, the iNOS expression becomes permanent and the corresponding NO/iNOS
      production is important to ensure an adequate maintenance of REM sleep and, to a
      lesser extent, SWS. Despite such maintenance, aged animals, however, are not able
      to elicit a sleep rebound to deal with the challenge of SD or IS. Sleep
      regulatory processes in adult animals thus become impaired with age. Reduced iNOS
      expression during aging may contribute to accelerated senescence, as observed in
      senescence-accelerated mice (SAMP-8 mice).

PMID- 22406307
TI  - Three-dimensional kinematics of saccadic and pursuit eye movements in humans:
      relationship between Donders' and Listing's laws.
AB  - For Listing's law to be obeyed during eye movements, the "half-angle rule" must
      be satisfied: the eye velocity axis must tilt away from Listing's plane by half
      the angle of eye position eccentricity from primary position. We aimed to
      determine if this rule is satisfied during horizontal and vertical pursuit
      compared with saccades. Three-dimensional (3-d) eye rotation data were acquired
      from five normal head-fixed humans using the search coil technique. Saccades were
      recorded in response to 40 degrees  horizontal or vertical steps in target
      position, at different elevations and azimuths. Pursuit was recorded while
      tracking a target moving horizontally or vertically at 20 degrees /s, with peak
      to-peak amplitude of 40 degrees , at the same elevations and azimuths. First- and
      second-order surfaces were fitted to 3-d eye position data from periods of
      fixation. In all subjects, eye positions did not lie on a planar surface, but on
      a twisted surface in 3-d space. The tilt-angle coefficient (TAC) during saccades
      and pursuit was calculated as the ratio of the angle of eye velocity axis tilt to
      the angle of eye position eccentricity. During horizontal saccades and pursuit,
      mean TACs were 0.58 and 0.64, respectively. During vertical saccades and pursuit,
      mean TACs were 0.35 and 0.43, respectively, and lower than their horizontal
      counterparts (p<0.05). These findings suggest that Listing's law is not perfectly
      satisfied during saccades or pursuit. On the basis of model simulations, we
      propose that the discrepancy in horizontal and vertical TACs causes eye positions
      to lie on a twisted rather than a planar surface.

PMID- 22406308
TI  - Temporal dynamics of the Venetian blind effect.
AB  - When square wave gratings are viewed binocularly with lower luminance or contrast
      in one eye, the individual bars of the grating appear to rotate around a vertical
      axis (Venetian blind effect). The effect has typically been thought to occur due
      to retinal disparities that result from irradiation and, therefore, are entirely
      entoptic. If so, the visual system should process disparities from a luminance or
      contrast disparity and a geometric disparity at the same rate. Studies of motion
      in-depth using geometric disparities have shown that the visual system is unable
      to process depth cues when those cues are oscillated at frequencies greater than
      5 Hz. By changing contrast (experiments one and two) and geometric (experiment
      three) disparity cues over time, the present study measured the frequency at
      which both the perception of motion-in-depth and the perception of depth
      diminish. The perception of motion-in-depth from contrast disparities decreased
      near 1.1 Hz (experiments one and four) and the perception of depth from contrast
      disparities decreased near 1.3 Hz (experiments one, two and four); both of which
      are lower than the frequency where depth from a geometric disparity diminished
      (near 4.8 Hz in experiment three). The differences between the dynamics of depth
      from contrast and geometric disparities suggest that the perception arises from
      separate neural mechanisms.

PMID- 22406309
TI  - Nitric oxide (NO) expression during annual reproductive activity in buffalo
      epididymis: a histochemical and immunocytochemical study.
AB  - The buffalo is one of the few domestic animals that has a seasonal mating cycle,
      influenced by the photoperiod. It is known that the photoperiod regulates gonadal
      function probably via the pineal and/or hypothalamus-pituitary axis. Moreover,
      the hypothalamus (melatonin) and gonads influence the production of the signaling
      transmitter nitric oxide (NO), suggesting that the NO may have an important role
      in the regulation of gonadotropin-releasing hormone secretion. This further
      suggests the hypothesis that NO in the epididymis has an important role in the
      maturation of spermatozoa and their motility and posterior fertilization
      capacity. The aim of the present study is to investigate the seasonal variations
      in the morphology of the epididymis by means histochemical and immunocytochemical
      techniques. We used the NADPH-d, nitric oxide synthase (NOS) I and NOS III to
      clarify the relationship between epididymis function and NO signaling activity.
      The results of this work show that NO is present in the caput of epididymis
      during short photoperiods, i.e., periods of maximum gonadal activity (winter) and
      absent during long photoperiods, i.e., periods of gonadal regression according to
      the previously described role of NO in spermatozoa capacitation and motility in
      the caput epididymis.

PMID- 22406310
TI  - Functional and anatomical remodeling in human retinal detachment.
AB  - Rhegmatogenous retinal detachment is by far the most common indication for
      retinal surgery and a major cause of severe vision loss. Increased levels of
      glutamate found in the vitreous of human patients and persistent remodeling, even
      after reattachment, suggest substantial neurochemical, functional and anatomical
      changes have occurred in the detached retina. Therefore, this study was designed
      to characterize the morphological changes and glutamate receptor functionality in
      human rhegmatogenous retinal detachment. A cation channel permeating probe,
      agmatine (1-amino-4-guanidobutane; AGB), was employed to track endogenous and
      kainate (KA) driven channel functionality combined with immunocytochemical
      characterization of cellular remodeling. In the detached retina increased AGB
      permeability was identified in the outer retina while there was a decrease in the
      inner retina in basal conditions. KA receptors exhibited increased AGB
      permeability in ON bipolar cells and decreased permeability in calbindin labeled
      inner retinal cells. All retinal detachment samples demonstrated ectopic synaptic
      protein expression, photoreceptor processes extending toward the inner retina,
      and other remodeling features of retinal degeneration. These anatomical changes
      have been demonstrated in animal studies and are novel features unreported in
      primary cases of human retinal detachment. We conclude that deafferentation in
      retinal detachment leads to alteration of the glutamatergic pathway.

PMID- 22406311
TI  - Investigating differential binding of polychlorinated dibenzo-p
      dioxins/dibenzofurans in soil and soil components using selective supercritical
      fluid extraction.
AB  - Supercritical fluid extraction (SFE) with pure carbon dioxide was performed at
      increasingly strong conditions to investigate differential binding of
      polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) in two impacted soils,
      in their sieved size fractions, and in small (a few mg) samples of industry
      related waste products separated from impacted soil. The binding strengths of
      PCDD/Fs were shown to be different in the two soils, and in their different soil
      particle size fractions. As might be expected based on surface area
      considerations, one soil showed the strongest binding in the smallest (<5MUm)
      sieved fraction. However, the other soil showed the strongest binding in the
      larger sized fractions, possibly indicating that process-related particles could
      be controlling PCDD/F binding. Selective SFE of various types of particles
      including black carbon and charcoal (separated from soil), and from a suspected
      process anode residue did show different PCDD/F binding behavior ranging from
      quite weak binding (charcoal) to very strong binding (anode particles). Shifts to
      the stronger SFE fractions in the soils after activated carbon treatment agreed
      well with the decreases previously found in the uptake of PCDD/Fs by earthworms,
      as well as decreases in their freely-dissolved aqueous concentrations in
      soil/water slurries. These results show that, as previously demonstrated for PAHs
      and PCBs, selective SFE can be a useful tool to investigate differences in PCDD/F
      binding behaviors in impacted soils and sediments and their component parts, as
      well as a rapid tool for estimating the effectiveness of activated carbon
      treatments on decreasing the bioavailability of PCDD/Fs in soils and sediments.

PMID- 22406312
TI  - Biomonitoring marine habitats in reference to antibiotic resistant bacteria and
      ampicillin resistance determinants from oviductal fluid of the nesting green sea
      turtle, Chelonia mydas.
AB  - During the egg-laying process, oviductal fluid was collected using a non-invasive
      procedure from the cloacal vent of the green turtles. Forty-two independent
      isolates of antibiotic-resistant bacteria from 11 genera were obtained from 20
      turtles during nesting. The dominant isolate was Citrobacter (52.4%), followed by
      Pseudomonas, Proteus, Enterobacter, Salmonella, Escherichia coli, Shigella,
      Edwardsiella, Morganella, Providencia and Arcomobacter. Most of the isolates were
      resistant to ampicillin. Ampicillin-resistant isolates showed variations in their
      resistance for the following classes of beta-lactamases: extended-spectrum beta
      lactamases (EBSLs), AmpC type beta-lactamases C (AmpC), and screen-positive beta
      lactamase. None of the isolates produced metallo beta-lactamase. Some ampicillin
      resistant genes were detected by multiplex polymerase chain reaction (PCR) only.
      Inhibitor based test (IBT) categorized some isolates as AmpC beta-lactamase
      producers. beta-Lactamase genes were detected from a few strains. The sequencing
      of those genes revealed the presence of cephamycinase (CMY) and AmpC beta
      lactamases. The oviductal fluid was used in this study as a source of bacterial
      antibiotic-resistant determinants for biomonitoring marine turtles exposed to
      contaminated effluents. This data can be of value in understanding the decline of
      this endangered species as a result of exposure to marine pollution which is
      threatening their survival.

PMID- 22406313
TI  - Neurophysiological analyses of asterixis utilizing innovative approaches.

PMID- 22406314
TI  - Relaxation dynamics of a protein solution investigated by dielectric
      spectroscopy.
AB  - In the present work, we provide a dielectric study on two differently
      concentrated aqueous lysozyme solutions in the frequency range from 1MHz to 40GHz
      and for temperatures from 275 to 330K. We analyze the three dispersion regions,
      commonly found in protein solutions, usually termed beta-, gamma-, and delta
      relaxations. The beta-relaxation, occurring in the frequency range around 10MHz
      and the gamma-relaxation around 20GHz (at room temperature) can be attributed to
      the rotation of the polar protein molecules in their aqueous medium and the
      reorientational motion of the free water molecules, respectively. The nature of
      the delta-relaxation, which is often ascribed to the motion of bound water
      molecules, is not yet fully understood. Here we provide data on the temperature
      dependence of the relaxation times and relaxation strengths of all three detected
      processes and on the dc conductivity arising from ionic charge transport. The
      temperature dependences of the beta- and gamma-relaxations are closely
      correlated. We found a significant temperature dependence of the dipole moment of
      the protein, indicating conformational changes. Moreover we find a breakdown of
      the Debye-Stokes-Einstein relation in this protein solution, i.e., the dc
      conductivity is not completely governed by the mobility of the solvent molecules.
      Instead it seems that the dc conductivity is closely connected to the hydration
      shell dynamics.

PMID- 22406315
TI  - Cation-leak stomatocytosis in standard schnauzers does not cosegregate with
      coding mutations in the RhAG, SLC4A1, or GLUT1 genes associated with human
      disease.
AB  - Autosomal dominant overhydrated cation-leak stomatocytosis in humans has been
      associated with missense mutations in the erythroid membrane transport genes AE1,
      RhAG, and GLUT1. Syndromic stomatocytosis has been reported in three dog breeds,
      but stomatocytosis in Standard Schnauzers is usually asymptomatic, and is
      accompanied by minimal if any anemia. We have extended the evaluation of a cohort
      of schnauzers. We found that low-level stomatocytosis was accompanied by
      increased MCV and increased red cell Na content, and minimal or no
      reticulocytosis. Red cells from two affected dogs exhibited increased currents in
      on-cell patches measured in symmetrical NaCl solutions, but Na,K-ATPase and NKCC
      mediated cation flux was minimal. Three novel coding polymorphisms found in
      canine RhAG cDNA and three novel polymorphisms found in canine SLC4A1 cDNA did
      not cosegregate with MCV or Na content. The GLUT1 cDNA sequence was normal. We
      conclude that unlike human overhydrated cation-leak stomatocytosis,
      stomatocytosis in this cohort of Standard Schnauzers is not caused by mutations
      in the genes encoding RhAG, SLC4A1, or GLUT1.

PMID- 22406317
TI  - Superoxide plays critical roles in electrotaxis of fibrosarcoma cells via
      activation of ERK and reorganization of the cytoskeleton.
AB  - Direct-current electrical field (DCEF) induces directional migration in many cell
      types by activating intracellular signaling pathways. However, the mechanisms
      coupling the extracellular electric stimulation to the intracellular signals
      remain largely unknown. In this study, we show that DCEF directs migration of HT
      1080 fibrosarcoma cells to the cathode, stimulates generation of hydrogen
      peroxide and superoxide through the activation of NADPH oxidase, induces anode
      facing cytoskeleton polarization, and activates ERK signaling. Subsequent studies
      demonstrate that the electrotaxis of HT-1080 fibrosarcoma cells is abolished by
      NADPH oxidase inhibitor and overexpression of manganese superoxide dismutase
      (MnSOD), an enzyme that hydrolyzes superoxide. In contrast, overexpression of
      catalases, which hydrolyze hydrogen peroxide, does not affect electrotaxis. MnSOD
      overexpression also eliminates cytoskeleton polarization as well as the
      activation of AKT, ERKs, and p38. In contrast, under catalase overexpression, the
      cytoskeleton still polarizes and p38 activation is affected. Finally, we show
      that inhibition of ERK activation also abolishes DCEF-induced directional
      migration and cytoskeleton polarization. Collectively, our results indicate that
      superoxide plays critical roles in DCEF-induced directional migration of
      fibrosarcoma cells, possibly by regulating the activation of ERKs. This study
      provides novel insights into the current understanding of DCEF-mediated cancer
      cell directional migration and metastasis.

PMID- 22406316
TI  - The role of death effector domain-containing proteins in acute oxidative cell
      injury in hepatocytes.
AB  - Apoptosis is a mechanism that regulates hepatic tissue homeostasis and
      contributes to both acute and chronic injury in liver disease. The apoptotic
      signaling cascade involves activation of the death-inducing signaling complex
      (DISC) and subsequent recruitment of proteins containing death effector domains
      (DED), which regulate downstream effector molecules. Prominent among these are
      the Fas-associated death domain (FADD) and the cellular caspase 8-like inhibitory
      protein (cFLIP), and alterations in these proteins can lead to severe disruption
      of physiological processes, including acute liver failure or hepatocellular
      carcinoma. Their role in cell signaling events independent of the DISC remains
      undetermined. Oxidative stress can cause cell injury from direct effects on
      molecules or by activating intracellular signaling pathways including the mitogen
      activated protein kinases (MAPKs). In this context, prolonged activation of the
      cJun N-terminal kinase (JNK)/AP-1/cJun signaling pathway promotes hepatocellular
      apoptosis, whereas activation of the extracellular signal-regulated kinase (Erk)
      exerts protection. We investigated the roles of FADD and cFLIP in acute oxidant
      stress induced by the superoxide generator menadione in hepatocytes. Menadione
      resulted in dose-dependent predominantly necrotic cell death. Hepatocytes
      expressing a truncated, dominant-negative FADD protein were partially protected,
      whereas cFLIP-deficient hepatocytes displayed increased cell death from
      menadione. In parallel, Erk phosphorylation was enhanced in hepatocytes
      expressing dnFADD and decreased in cFLIP-deficient hepatocytes. Hepatocyte injury
      was accompanied by increased release of proapoptotic factors and increased
      JNK/cJun activation. Thus, FADD and cFLIP contribute to the regulation of cell
      death from acute oxidant stress in hepatocytes involving MAPK signaling. This
      implies that DED-containing proteins are involved in the regulation of cellular
      survival beyond their role in cell death receptor-ligand-mediated apoptosis.

PMID- 22406318
TI  - Fast repair of protein radicals by urate.
AB  - The repair of tryptophan and tyrosine radicals in proteins by urate was studied
      by pulse radiolysis. In chymotrypsin, urate repairs tryptophan radicals
      efficiently with a rate constant of 2.7 * 10(8)M(-1)s(-1), ca. 14 times higher
      than the rate constant derived for N-acetyltryptophan amide, 1.9 * 10(7)M(-1)s(
      1). In contrast, no repair of tryptophan radicals was observed in pepsin, which
      indicates a rate constant smaller than 6 * 10(7)M(-1)s(-1). Urate repairs
      tyrosine radicals in pepsin with a rate constant of 3 * 10(8)M(-1)s(-1)-ca. 12
      times smaller than the rate constant reported for free tyrosine-but not in
      chymotrypsin, which implies an upper limit of 1 * 10(6)M(-1)s(-1) for the
      corresponding rate constant. Intra- and intermolecular electron transfer from
      tyrosine residues to tryptophan radicals is observed in both proteins, however,
      to different extents and with different rate constants. Urate inhibits electron
      transfer in chymotrypsin but not in pepsin. Our results suggest that urate
      repairs the first step on the long path to protein modification and prevents
      damage in vivo. It may prove to be a very important repair agent in tissue
      compartments where its concentration is higher than that of ascorbate. The
      product of such repair, the urate radical, can be reduced by ascorbate. Loss of
      ascorbate is then expected to be the net result, whereas urate is conserved.

PMID- 22406319
TI  - Off-target thiol alkylation by the NADPH oxidase inhibitor 3-benzyl-7-(2
      benzoxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine (VAS2870).
AB  - Specific inhibitors of the production of reactive oxygen species (ROS) by the
      NADPH oxidases (Nox's) are potentially important therapeutic agents in the wide
      range of human diseases that are characterized by excessive ROS production. It
      has been proposed that VAS2870 (3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-
      triazolo[4,5-d]pyrimidine), identified as an inhibitor of Nox2 by small-molecule
      screening, may serve as an example of such an agent. Here we show that VAS2870
      inhibits ROS production in the sarcoplasmic reticulum (SR) of mammalian skeletal
      muscle, previously identified with Nox4, and thereby abrogates O(2)-coupled redox
      regulation of the ryanodine receptor-Ca(2+) channel (RyR1). However, we also find
      that VAS2870 modifies directly identified cysteine thiols within RyR1. Mass
      spectrometric analysis of RyR1 exposed in situ to VAS2870 and of VAS2870-treated
      glutathione indicated that thiol modification is through alkylation by the
      benzyltriazolopyrimidine moiety of VAS2870. Thus, VAS2870 exerts significant off
      target effects, and thiol alkylation by VAS2870 (and closely related Nox
      inhibitors) may in fact replicate some of the effects of ROS on cellular thiol
      redox status. In addition, we show that SR-localized Nox4 is inhibited by other
      thiol-alkylating agents, consistent with a causal role for cysteine modification
      in the inhibition of ROS production by VAS2870.

PMID- 22406320
TI  - Molecular mechanisms of ALDH3A1-mediated cellular protection against 4-hydroxy-2
      nonenal.
AB  - Evidence suggests that aldehydic molecules generated during lipid peroxidation
      (LPO) are causally involved in most pathophysiological processes associated with
      oxidative stress. 4-Hydroxy-2-nonenal (4-HNE), the LPO-derived product, is
      believed to be responsible for much of the cytotoxicity. To counteract the
      adverse effects of this aldehyde, many tissues have evolved cellular defense
      mechanisms, which include the aldehyde dehydrogenases (ALDHs). Our laboratory has
      previously characterized the tissue distribution and metabolic functions of
      ALDHs, including ALDH3A1, and demonstrated that these enzymes may play a
      significant role in protecting cells against 4-HNE. To further characterize the
      role of ALDH3A1 in the oxidative stress response, a rabbit corneal keratocyte
      cell line (TRK43) was stably transfected to overexpress human ALDH3A1. These
      cells were studied after treatment with 4-HNE to determine their abilities to:
      (a) maintain cell viability, (b) metabolize 4-HNE and its glutathione conjugate,
      (c) prevent 4-HNE-protein adduct formation, (d) prevent apoptosis, (e) maintain
      glutathione homeostasis, and (f) preserve proteasome function. The results
      demonstrated a protective role for ALDH3A1 against 4-HNE. Cell viability assays,
      morphological evaluations, and Western blot analyses of 4-HNE-adducted proteins
      revealed that ALDH3A1 expression protected cells from the adverse effects of 4
      HNE. Based on the present results, it is apparent that ALDH3A1 provides
      exceptional protection from the adverse effects of pathophysiological
      concentrations of 4-HNE such as may occur during periods of oxidative stress.

PMID- 22406321
TI  - Oxidative protein folding and unfolded protein response elicit differing redox
      regulation in endoplasmic reticulum and cytosol of yeast.
AB  - Oxidative protein folding can exceed the cellular secretion machinery, inducing
      the unfolded protein response (UPR). Sustained endoplasmic reticulum (ER) stress
      leads to cell stress and disease, as described for Alzheimer, Parkinson, and
      diabetes mellitus, among others. It is currently assumed that the redox state of
      the ER is optimally balanced for formation of disulfide bonds using glutathione
      as the main redox buffer and that UPR causes a reduction of this organelle. The
      direct effect of oxidative protein folding in the ER, however, has not yet been
      dissected from UPR regulation. To measure in vivo redox conditions in the ER and
      cytosol of the yeast model organism Pichia pastoris we targeted redox-sensitive
      roGFP variants to the respective organelles. Thereby, we clearly demonstrate that
      induction of the UPR causes reduction of the cytosol in addition to ER reduction.
      Similarly, a more reduced redox state of the cytosol, but not of the ER, is
      observed during oxidative protein folding in the ER without UPR induction, as
      demonstrated by overexpressing genes of disulfide bond-rich secretory proteins
      such as porcine trypsinogen or protein disulfide isomerase (PDI1) and ER oxidase
      (ERO1). Cytosolic reduction seems not to be caused by the action of glutathione
      reductase (GLR1) and could not be compensated for by overexpression of cytosolic
      glutathione peroxidase (GPX1). Overexpression of GPX1 and PDI1 oxidizes the ER
      and increases the secretion of correctly folded proteins, demonstrating that
      oxidative protein folding per se is enhanced by a more oxidized ER and is
      counterbalanced by a more reduced cytosol. As the total glutathione concentration
      of these strains does not change significantly, but the ratio of GSH to GSSG is
      altered, either transport or redox signaling between the glutathione pools of ER
      and cytosol is assumed. These data clearly demonstrate that protein folding and
      ER stress have a severe impact on the cytosolic redox balance, which may be a
      major factor during development of folding-related diseases.

PMID- 22406322
TI  - Organotellurium and organoselenium compounds attenuate Mn-induced toxicity in
      Caenorhabditis elegans by preventing oxidative stress.
AB  - Organochalcogens have been widely studied given their antioxidant activity, which
      confers neuroprotection, antiulcer, and antidiabetic properties. Given the
      complexity of mammalian models, understanding the cellular and molecular effects
      of organochalcogens has been hampered. The nematode worm Caenorhabditis elegans
      is an alternative experimental model that affords easy genetic manipulations,
      green fluorescent protein tagging, and in vivo live analysis of toxicity. We
      previously showed that manganese (Mn)-exposed worms exhibit oxidative-stress
      induced neurodegeneration and life-span reduction. Here we use Mn-exposed worms
      as a model for an oxidatively challenged organism to investigate the underlying
      mechanisms of organochalcogen antioxidant properties. First, we recapitulate in
      C. elegans the effects of organochalcogens formerly observed in mice, including
      their antioxidant activity. This is followed by studies on the ability of these
      compounds to afford protection against Mn-induced toxicity. Diethyl-2-phenyl-2
      tellurophenyl vinyl phosphonate (DPTVP) was the most efficacious compound, fully
      reversing the Mn-induced reduction in survival and life span. Ebselen was also
      effective, reversing the Mn-induced reduction in survival and life span, but to a
      lesser extent compared with DPTVP. DPTVP also lowered Mn-induced increases in
      oxidant levels, indicating that the increased survival associated with exposure
      to this compound is secondary to a decrease in oxidative stress. Furthermore,
      DPTVP induced nuclear translocation of the transcriptional factor DAF-16/FOXO,
      which regulates stress responsiveness and aging in worms. Our findings establish
      that the organochalcogens DPTVP and ebselen act as antiaging agents in a model of
      Mn-induced toxicity and aging by regulating DAF-16/FOXO signaling and attenuating
      oxidative stress.

PMID- 22406323
TI  - The infant behavioral assessment and intervention program in very low birth
      weight infants; outcome on executive functioning, behaviour and cognition at
      preschool age.
AB  - BACKGROUND: The Infant Behavioral Assessment and Intervention Program (IBAIP(c))
      improved motor function at 24 months, and mental and behavioural development in
      high risk subgroups of very low birth weight (VLBW) infants. AIM: To determine
      IBAIP's effects on executive functioning, behaviour and cognition at preschool
      age. STUDY DESIGN: Follow-up of a randomised controlled trial (RCT). SUBJECTS: At
      44 months corrected age, all 176 VLBW infants were invited for follow-up. Forty
      one term born children were assessed for comparison. OUTCOME MEASURES: Visual
      Attention Task (VAT), Gift delay, Peabody Picture Vocabulary Test III-NL (PPVT),
      Visual motor integration tests and Miller assessment for preschoolers. Parents
      completed Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) and
      Child Behavior Checklist (CBCL). RESULTS: At preschool age, 76 (88%) children of
      the intervention group and 75 (83%) children of the control group participated.
      There were no significant differences between the intervention and the control
      group. However, positive interaction effects between intervention and infants
      with bronchopulmonary dysplasia, infants born at gestational age<28 weeks, and
      infants of low educated mothers were found on CBCL, CBCL and BRIEF-P, and PPVT
      respectively. Most interaction effects exceeded 1 standard deviation in favour of
      the intervention children. The 151 VLBW children performed significantly worse
      than the term born children on the VAT, BRIEF-P and CBCL. CONCLUSION: IBAIP
      effects in VLBW children did not sustain until preschool age on executive
      functioning, behaviour and cognition. However, the most vulnerable children had a
      clinical relevant profit from IBAIP. VLBW children performed worse than the term
      born children. This study is a follow-up at preschool age of the multi-centre RCT
      of IBAIP versus usual care in VLBW infants. The RCT was performed in Amsterdam,
      The Netherlands (IBAIP).

PMID- 22406324
TI  - Construction and characterization of the infectious clone of
      Reticuloendotheliosis virus carrying a genetic marker.
AB  - Reticuloendotheliosis virus (REV) causes an immunosuppressive and oncogenic
      disease, which posed substantial threats to the commercial poultry industry.
      However, researches on the molecular epidemiology and the pathogenic mechanism of
      REV are still scant. In this study, a full-length genome cDNA of
      Reticuloendotheliosis virus (REV) strain HLJR0901, which was isolated from layer
      in China, was cloned, sequenced, and analyzed. The genome of HLJR0901 was 8284 bp
      long, and the GenBank accession number is GQ415646. Sequence analysis showed that
      HLJR0901 was more similar to some REV strains that are common in the USA and
      Taiwan than to the early Chinese REV isolate. Next, the first efficient and
      genetically stable infectious clone with the genetic markers of the layer strain
      of REV was developed. The rescued and parental viruses had similar biological
      characteristics in vitro and in vivo. This study not only contributes to novel
      molecular epidemiology data, but also facilitates researching the gene functions
      and evolution of REV.

PMID- 22406325
TI  - Molecular characterisation of dicot-infecting mastreviruses from Australia.
AB  - Monocotyledonous and dicotyledonous plant infecting mastreviruses threaten
      various agricultural systems throughout Africa, Eurasia and Australasia. In
      Australia three distinct mastrevirus species are known to infect dicotyledonous
      hosts such as chickpea, bean and tobacco. Amongst 34 new "dicot-infecting"
      mastrevirus full genome sequences obtained from these hosts we discovered one new
      species, four new strains, and various variants of previously described
      mastrevirus species. Besides providing additional support for the hypothesis that
      evolutionary processes operating during dicot-infecting mastrevirus evolution
      (such as patterns of pervasive homologous and non-homologous recombination, and
      strong purifying selection acting on all genes) have mostly mirrored those found
      in their monocot-infecting counterparts, we find that the Australian dicot
      infecting viruses display patterns of phylogeographic clustering reminiscent of
      those displayed by monocot infecting mastrevirus species such as Panicum streak
      virus and Maize streak virus.

PMID- 22406326
TI  - Lupeol protects against acetaminophen-induced oxidative stress and cell death in
      rat primary hepatocytes.
AB  - Drug induced hepatotoxicity is a major problem where phytochemicals hold promise
      for its abrogation. This study was carried out to explore cytoprotective
      potential of lupeol, a triterpene, against acetaminophen (AAP)-induced toxicity
      in rat hepatocytes. AAP exposure significantly (p<0.05) reduced cell viability,
      disturbed Bcl-2 family pro/anti-apoptotic protein balance, increased ROS
      production and altered redox homeostasis. It also induced mitochondria-mediated
      hepatocellular injury by significant mitochondrial depolarization, caspase-9/3
      activation and subsequent DNA fragmentation. Our results suggest that lupeol pre
      treatment effectively restored antioxidant enzyme levels, decreased lipid
      peroxidation, inhibited ROS generation and depolarization of mitochondria. Lupeol
      also attenuated mitochondria-mediated signaling pathway and DNA damage as evident
      from TUNEL assay and cell cycle studies leading to prevention of cytotoxicity.
      This study confirms the efficacy of lupeol, a food derived antioxidant, in
      abrogating ROS generation, maintaining redox balance and providing significant
      protection against mitochondria-mediated cell death during AAP-induced toxicity.

PMID- 22406327
TI  - Bioaccessibility of cadmium in fresh and cooked Agaricus blazei Murill assessed
      by in vitro biomimetic digestion system.
AB  - Bioaccessibility of cadmium (Cd) in fresh and cooked Agaricus blazei Murill (AbM)
      was studied by an in vitro biomimetic digestion system in this paper. The results
      showed that the Cd content in fresh AbM was 10.27 mg kg(-1) DM. The cooking
      treatments of boiling and microwaving with water significantly decreased Cd
      contents in fresh AbM by 36.4% and 30.2% (P<0.05), respectively. Cd in fresh AbM
      showed the highest bioaccessibility of 77.8% during the biomimetic digestion in
      stomach, followed by that of 69.4% from the gastrointestinal digestion. Cooking
      treatments also significantly lowered the bioaccessibility of Cd (P<0.05). Cd in
      boiled AbM showed 50.7% and 46.1% bioaccessibility during the gastric and
      gastrointestinal procedures. While, Cd in microwaved AbM showed 58.2% and 50.4%
      bioaccessibility. This study confirmed that the health risk assessment of AbM
      depending on the total Cd levels in fresh AbM was inaccurate, especially for the
      products domestically cooked.

PMID- 22406328
TI  - Toxicokinetics and lack of uterotropic effect of orally administered S-equol.
AB  - S-equol is a natural product that is produced by the microbial biotransformation
      of daidzein, an isoflavone found in soy. Evidence suggests that the health
      benefits of soy may be related to one's ability to produce S-equol, thus S-equol
      is being developed for the treatment of vasomotor symptoms in postmenopausal
      women. The toxicokinetics of S-equol were evaluated in Sprague-Dawley rats and
      cynomolgus monkeys; S-equol was rapidly absorbed with C(max) occurring between
      0.5 h and 1.0 h in the rat and 3h in the monkey. AUC was linear over the doses
      tested with no differences between male and female animals. Conjugated S-equol
      was the major metabolite in plasma with less than 1% present as the unconjugated
      form. S-equol showed a weak induction of liver cytochrome P450s in vivo, and did
      not significantly inhibit the major human cytochrome P450s in vitro. S-equol was
      highly protein bound (>95%) in rat, monkey and man in a concentration-independent
      manner. Orally administered S-equol did not significantly change uterine weight
      or morphology in either the rat or monkey even at the highest doses tested. These
      studies show that S-equol has pharmacokinetic parameters suitable for drug
      development with a low potential for uterotropic effects.

PMID- 22406329
TI  - Heating of BDE-209 and BDE-47 in plant oil in presence of o,p'-DDT or iron(III)
      chloride can produce monochloro-polybromo diphenyl ethers.
AB  - Heating processes of food can alter the concentrations and composition of
      organohalogen compounds. In this study the fate of two polybrominated diphenyl
      ether (PBDE) congeners, decabromodiphenyl ether (BDE-209) and 2,2',4,4'
      tetrabromodiphenyl ether (BDE-47) was analyzed when heated in plant oil with and
      without additional compounds. When the PBDEs were heated in pure plant oil, no
      transformation was observed. Heating of decabromodiphenyl ether (BDE-209)
      together with ortho,para'-dichlorodiphenyltrichloroethane (o,p'-DDT) or iron(III)
      chloride in plant oil resulted in the formation of monochloro-nonabromodiphenyl
      ethers (Br(9)Cl-DEs). Almost 10% of the initial amount of BDE-209 was transferred
      into Br(9)Cl-DEs. Heating BDE-47 in the presence of iron(III) chloride produced
      two monochlorinated transformation products which were tentatively identified as
      2,2',4-tribromo-4'-chlorodiphenyl ether (4'-Cl-BDE-17) and 2,4,4'-tribromo-2'
      chlorodiphenyl ether (2'-Cl-BDE-28). However, the reactivity was smaller and no
      Br->Cl exchange was observed with o,p'-DDT. The conditions used in our
      experiments (200  degrees C; heating 30 min-3 h) indicate that such reactivity
      may also occur during cooking of fish, meat and other food samples.

PMID- 22406330
TI  - Does switching to a tobacco-free waterpipe product reduce toxicant intake? A
      crossover study comparing CO, NO, PAH, volatile aldehydes, "tar" and nicotine
      yields.
AB  - Waterpipe (hookah, narghile, shisha) use has become a global phenomenon, with
      numerous product variations. One variation is a class of products marketed as
      "tobacco-free" alternatives for the "health conscious user". In this study
      toxicant yields from waterpipes smoked using conventional tobacco-based and
      tobacco-free preparations were compared. A human-mimic waterpipe smoking machine
      was used to replicate the puffing sequences of 31 human participants who
      completed two double-blind ad libitum smoking sessions in a controlled clinical
      setting: once with a tobacco-based product of their choosing and once with a
      flavor-matched tobacco-free product. Outcome measures included yields of carbon
      monoxide, nitric oxide, volatile aldehydes, nicotine, tar, and polycyclic
      aromatic hydrocarbons. Smoke from both waterpipe preparations contained
      substantial quantities of toxicants. Nicotine yield was the only outcome that
      differed significantly between preparations. These findings contradict
      advertising messages that "herbal" waterpipe products are a healthy alternative
      to tobacco products.

PMID- 22406331
TI  - Magnetic micelles as a potential platform for dual targeted drug delivery in
      cancer therapy.
AB  - The magnetic nanomicelles as a potential platform for dual targeted (folate
      mediated and magnetic-guided) drug delivery were developed to enhance the
      efficiency and veracity of drug delivering to tumor site. The magnetic
      nanocarriers were synthesized based on superparamagnetic iron oxide nanoparticles
      (SPIONs), biocompatible Pluronic F127 and poly(dl-lactic acid) (F127-PLA)
      copolymer chemically conjugated with tumor-targeting ligand-folic acid (FA) via a
      facile chemical conjugation method. Doxorubicin hydrochloride (DOX.HCl) was
      selected as a model anticancer drug to investigate the in vitro drug release and
      antiproliferative effect of tumor cells in vitro and in vivo in the presence or
      absence of an external magnetic filed (MF) with strength of 0.1T. The Alamar blue
      assay exhibited that these magnetic nanomicelles possessed remarkable cell
      specific targeting in vitro. Additionally this smart system enabling folate
      receptor-mediated uptake into tumor cells, showed strong responsiveness to MF.
      The primary in vivo tumor model study, which was carried out in VX2 tumor-bearing
      male New Zealand white rabbits, demonstrated that the nanomicelles could be
      guided into tumor site more efficiently by application of MF, and further
      represented significant therapeutic efficiency to solid tumor.

PMID- 22406332
TI  - Malaria parasite colonisation of the mosquito midgut--placing the Plasmodium
      ookinete centre stage.
AB  - Vector-borne diseases constitute an enormous burden on public health across the
      world. However, despite the importance of interactions between infectious
      pathogens and their respective vector for disease transmission, the biology of
      the pathogen in the insect is often less well understood than the forms that
      cause human infections. Even with the global impact of Plasmodium parasites, the
      causative agents of malarial disease, no vaccine exists to prevent infection and
      resistance to all frontline drugs is emerging. Malaria parasite migration through
      the mosquito host constitutes a major population bottleneck of the lifecycle and
      therefore represents a powerful, although as yet relatively untapped, target for
      therapeutic intervention. The understanding of parasite-mosquito interactions has
      increased in recent years with developments in genome-wide approaches, genomics
      and proteomics. Each development has shed significant light on the biology of the
      malaria parasite during the mosquito phase of the lifecycle. Less well
      understood, however, is the process of midgut colonisation and oocyst formation,
      the precursor to parasite re-infection from the next mosquito bite. Here, we
      review the current understanding of cellular and molecular events underlying
      midgut colonisation centred on the role of the motile ookinete. Further insight
      into the major interactions between the parasite and the mosquito will help
      support the broader goal to identify targets for transmission-blocking therapies
      against malarial disease.

PMID- 22406333
TI  - Aripiprazole in pediatric psychosis and bipolar disorder: a clinical review.
AB  - BACKGROUND: Aripiprazole is an atypical antipsychotic with unique pharmacological
      properties, used for a variety of indications, including psychotic and mood
      disorders in youth. Existing literature was reviewed to summarize experience with
      this agent in that population. METHODS: A review of relevant literature using the
      key words aripiprazole, children, pediatric, all child, schizophrenia, bipolar
      disorder, and atypical antipsychotics was conducted. RESULTS: A total of 140
      articles and book chapters were identified, of which 7 reported double-blind
      controlled trials with aripiprazole, 5 were meta-analyses of pooled data, 11 were
      open label trials, 10 were chart reviews, and 17 were case reports or case
      series. LIMITATIONS: Although every effort was made to locate all available data,
      some information from posters or researchers was not available. Publication bias
      tends to report positive outcomes with a treatment, while negative studies are
      less likely to be reported. Most trials are of short duration. CONCLUSIONS:
      Treatment with aripiprazole is associated with significant reduction of the
      Positive and Negative Symptom Scale (PANSS) scores in youth with schizophrenia,
      and reductions in items in the negative symptom scores at higher doses (30
      mg/day). Significant reductions in the Young Mania Rating Scale (YMRS) have been
      demonstrated in youth with bipolar disorder. In mixed populations, reductions in
      the Clinical Global Impressions Scale (CGI-S) have also been demonstrated when
      compared with treatment with placebo. Head-to-head comparisons are fewer in
      number, and overall aripiprazole compares favorably with other atypical
      antipsychotics (ATAs) in the populations studied. Treatment with aripiprazole is
      reported to have a lower incidence of weight gain, and less elevation of
      prolactin. At higher doses, it appears more likely to result in extrapyramidal
      symptoms (EPS) and tremor.

PMID- 22406334
TI  - Towards a multifactorial approach for prediction of bipolar disorder in at risk
      populations.
AB  - BACKGROUND: The high prevalence, recurrence rate, chronicity, and illness burden
      in bipolar disorder (BD) are well documented. Moreover, insufficient response
      with conventional pharmacological and manual-based psychosocial interventions, as
      well as evidence of illness progression and acceleration, invite the need for
      early detection and primary prevention. METHODS: Herein we comprehensively review
      extant studies reporting on a bipolar prodrome. The overarching aim is to propose
      a predictive algorithm (i.e. prediction of BD in at-risk populations) integrating
      genetic (i.e. family history), environmental (e.g. childhood maltreatment) and
      biological markers (i.e. BDNF, inflammatory and oxidative stress markers).
      Computerized databases i.e. Pubmed, PsychInfo, Cochrane Library and Scielo were
      searched using the followed terms: bipolar disorder cross-referenced with
      prodromal, preclinical, at risk mental states, clinical high risk, ultra high
      risk, biomarkers, brain-derived neurotrophic factor, inflammation, cytokines,
      oxidative stress, prediction and predictive model. RESULTS: Available evidence
      indicates that a prodrome to bipolar disorder exists. Commonly encountered
      features preceding the onset of a manic episode are affective lability,
      irritability, anger, depression, anxiety, substance use disorders, sleep
      disorders, as well as disturbances in attention and cognition. Non-specificity
      and insufficient sensitivity have hampered the development of an adequate
      prediction algorithm. LIMITATIONS: Limitations include biases associated with
      retrospective studies, poor characterization of clinical high risk, inadequacy of
      prospective studies regarding sample selection and absence of specificity of risk
      states. CONCLUSION: We propose a hypothetical prediction algorithm that is
      combinatorial in approach that attempts to integrate family history, early
      adversity, and selected biomarkers.

PMID- 22406335
TI  - Personal stigma, problem appraisal and perceived need for professional help in
      currently untreated depressed persons.
AB  - BACKGROUND: The role of stigma in help-seeking for depression is unclear. We
      hypothesize that in persons experiencing symptoms of depression, personal
      stigmatizing attitudes impair appraisal of the present condition as mental health
      problem and thus reduce the perceived need for professional help. METHODS: We
      recruited a sample of 25 currently untreated depressed persons from the general
      population using local newspaper articles and emails that listed symptoms of
      depression avoiding the term "depression" or any other potentially stigma
      associated term. We elicited personal stigmatizing attitudes, appraisal of the
      present problem as mental health problem, and perceived need for any medical or
      therapeutic help. RESULTS: In linear regression analyses controlling for
      depression severity and previous help-seeking, high personal stigma was related
      to lower problem appraisal (beta, -0.38; p<0.05) and to lower perceived need
      (beta, -0.59, p<0.01). Lower problem appraisal was associated with lower
      perceived need. Regressing need on both problem appraisal and stigma reduced the
      direct influence of stigma on need, indicating a partial mediation of this
      relationship by problem appraisal. LIMITATIONS: Our small sample prohibited the
      use of path models. CONCLUSIONS: Personal stigmatizing attitudes in persons
      suffering from a depressive syndrome pose an important barrier to help, impairing
      appraisal of depressive symptoms as potential mental health problem and
      decreasing perceived need for professional help.

PMID- 22406336
TI  - Preface: Use of medications for adolescents with psychotic and bipolar disorders.

PMID- 22406337
TI  - Bipolar depression: clinical correlates of receiving antidepressants.
AB  - BACKGROUND: The efficacy and tolerability of antidepressants (ADs) to treat or
      avoid episodes of depression in bipolar disorder (BPD) patients as well as
      reasons for using them remain unresolved. METHODS: We analyzed patient
      characteristics and outcomes of episodes of acute major depression among 290
      adult, DSM-IV BPD patients (71% type-I, 52% women) at the Hospital Clinic of
      Barcelona; 80% were given an AD and 20% were not; 80% of both groups also
      received mood-stabilizers. We evaluated factors associated with AD-treatment
      using bivariate analyses and multiple logistic-regression modeling. RESULTS:
      Factors associated with AD-use by multivariate modeling ranked: [a] more years
      ill, [b] depressive first-lifetime episode, [c] more depressions/year, [d]
      melancholic index episode, and [e] less affective illness in first-degree
      relatives. Within 8weeks, depression improved by >=50%, less often among BPD
      patients given an AD (64.4%; 38.6% without switching into hypo/mania) than not
      (82.1%; 78.6% without switching). CONCLUSIONS: Use of ADs to treat acute BP
      depression was very common and associated with a more severe clinical history.
      Mood-switching was prevalent with AD-treatment even with mood-stabilizers
      present.

PMID- 22406338
TI  - Suicidal ideation and the subjective aspects of depression.
AB  - BACKGROUND: Suicidal ideation is common in depression, but only moderately
      related to depression severity - in part because certain clusters of symptoms,
      such as those related to core mood disturbance, have a differential relationship
      to suicidal thinking. METHODS: 400 medication free participants with current
      major depression were assessed with either or both the Hamilton Depression Rating
      Scale (HDRS, n=396) and Beck Depression Inventory (BDI, n=366), and the Scale for
      Suicide Ideation (SSI). Depression rating scales were decomposed into symptoms
      clusters previously reported (Grunebaum et al., 2005), in order to evaluate their
      association to suicidal thinking. RESULTS: Correlations between overall
      depression severity ratings and the measure of suicidal ideation were modest, and
      reduced when specific items assessing suicidal thinking on these depression
      scales were removed. Symptom clusters assessing Psychic Depression (HDRS),
      Subjective Depression (BDI), and Self-Blame (BDI) were the strongest correlates
      of suicidal ideation; other somatic and vegetative symptoms had little or no
      association to suicidal ideation. Severity of these symptom clusters effectively
      discriminated those with (SSI>0) and without (SSI=0) ideation; severity of these
      symptom clusters was less strongly associated with the severity of ideation once
      ideation was present. LIMITATIONS: This is a cross-sectional study, and the
      dynamic relationship between changes in the severity of various depressive
      symptoms and change in suicidal thinking remains to be explored. CONCLUSIONS:
      Depression severity is moderately associated with suicidal ideation, and
      accounted for primarily by core mood disturbance symptoms and self-punitive
      thinking. These associations may explain why suicide risk might remain high
      during treatment even though somatic and vegetative symptoms improve.

PMID- 22406339
TI  - Identification and developmental profiling of conserved and novel microRNAs in
      Manduca sexta.
AB  - MicroRNAs (miRNAs) are a group of small RNAs involved in translation inhibition
      or mRNA degradation. Due to its large size, Manduca sexta has long been used as a
      model to study insect physiology and biochemistry. While transcriptome studies
      have greatly enriched our knowledge on M. sexta structural genes, little is known
      about posttranscriptional regulation by miRNAs in this lepidopteran species. We
      constructed four small RNA libraries from embryos, 4th instar feeding larvae,
      pupae, and adults, obtained 21 million reads of 18-31 nucleotides by Illumina
      sequencing, and found 163 conserved and 13 novel miRNAs. By searching the M.
      sexta genome assembly, we identified precursors of 82 conserved miRNAs, 76 of
      which had mapped reads in one or more of these libraries. After normalization, we
      compared numbers of miRNA and miRNA-star reads in these libraries and observed
      abundance changes during development. Interestingly, mse-miR-281-star, mse-miR-31
      star, mse-miR-965-star, mse-miR-9a-star, mse-miR-9b-star, mse-miR-2a-star, mse
      miR-92b-star and mse-miR-279c-star are either more abundant or maintained at
      similar levels compared to respective mature miRNA strand. Expression profiling
      of the first set of miRNAs provided insights to their possible involvement in
      developmental regulation. This study will aid in the annotation of miRNA genes in
      the genome.

PMID- 22406340
TI  - Structural basis for the assembly and disassembly of mRNA nuclear export
      complexes.
AB  - Most of the individual components of the nuclear elements of the gene expression
      pathway have been identified and high-resolution structural information is
      becoming available for many of them. Information is also starting to become
      available on the larger complexes they form and is beginning to give clues about
      how the dynamics of their interactions generate function. Although the
      translocation of export-competent messenger ribonucleoprotein particles (mRNPs)
      through the nuclear pore transport channel that is mediated by interactions with
      nuclear pore proteins (nucleoporins) is relatively well understood, the precise
      molecular mechanisms underlying the assembly of export-competent mRNPs in the
      nucleus and their Dbp5-mediated disassembly in the cytoplasm is less well
      defined. Considerable information has been obtained on the structure of Dbp5 in
      its different nucleotide-bound states and in complex with Gle1 or Nup159/NUP214.
      Although the precise manner by which the Dbp5 ATPase cycle is coupled to mRNP
      remodelling remains to be established, current models capture many key details of
      this process. The formation of export-competent mRNPs in the nucleus remains an
      elusive component of this pathway and the precise nature of the remodelling that
      generates these mRNPs as well as detailed understanding of the molecular
      mechanisms by which this step is integrated with the transcriptional, splicing
      and polyadenylation machinery by the TREX and TREX-2 complexes remain obscure.
      This article is part of a Special Issue entitled: Nuclear Transport and RNA
      Processing.

PMID- 22406342
TI  - From plant gene regulatory grids to network dynamics.
AB  - The regulation of gene expression is the most basic level at which genotypes
      encoded in DNA can manifest themselves into observable phenotypes. In eukaryotes,
      gene regulatory networks (GRNs) describe the regulatory web through which
      transcription factors and microRNAs tightly regulate the spatial and temporal
      expression of genes. In yeast, Escherichia coli, and animals the study of GRNs
      has uncovered many of the network properties responsible for creating complex
      regulatory behavior such as organism growth, development, and response to
      environmental stimuli. In plants, the study of GRNs is just starting to gain
      momentum thanks to new high quality genomes and the development of new tools for
      GRN mapping. Here, we review the latest advancements in the study of plant GRNs
      and describe the tools and techniques used to produce them. We also discuss the
      emerging field of network dynamics and the methods currently being developed to
      measure network dynamics and function in plants.

PMID- 22406341
TI  - Coupling polymerase pausing and chromatin landscapes for precise regulation of
      transcription.
AB  - Altering gene expression in response to stimuli is a pivotal mechanism through
      which organisms execute developmental programs and respond to changes in their
      environment. Packaging of promoter DNA into chromatin can greatly impact the
      ability of RNA polymerase II to access and transcribe a gene. Promoter chromatin
      environments thus play a central role in establishing transcriptional output
      appropriate for specific environmental conditions or developmental states. Recent
      genomic studies have illuminated general principles of chromatin organization and
      deepened our understanding of how promoter sequence and nucleosome architecture
      may impact gene expression. Concurrently, pausing of polymerase during early
      elongation has been recognized as an important event influencing transcription of
      genes within stimulus-responsive networks. Promoters regulated by pausing are now
      recognized to possess a distinct chromatin architecture that may facilitate the
      plasticity of gene expression in response to signaling events. Here we review
      advances in understanding chromatin and pausing, and explore how coupling Pol II
      pausing to distinct promoter architectures may help organisms achieve flexible
      yet precise transcriptional control. This article is part of a Special Issue
      entitled: Chromatin in time and space.

PMID- 22406343
TI  - Results of the 2nd scientific workshop of the ECCO (IV): therapeutic strategies
      to enhance intestinal healing in inflammatory bowel disease.
AB  - Evidence supporting the importance of assessment of mucosal healing in
      inflammatory bowel disease has increased in the last years. Mucosal healing has
      been integrated in the assessment of treatment efficacy in ulcerative colitis,
      but in Crohn's disease this thought has arised after biological agents have been
      evaluated in clinical trials. Although a validated definition of mucosal healing
      still does not exist, its use is also assuming an increasingly important role in
      the follow-up of individual patients in clinical practice. Corticosteroids induce
      mucosal healing in a small proportion of patients with Crohn's disease and are of
      no benefit to maintain it. By contrast, mucosal healing in Crohn's disease can be
      achieved and maintained, with varying degrees of evidence and success, with
      thiopurines and biological agents. In ulcerative colitis, the ability of
      corticosteroids to induce mucosal healing is well recognized. 5-aminosalicylates,
      thiopurines and biological agents are also able to induce mucosal healing and,
      additionally, to maintain it. Mucosal healing assessment should be considered in
      clinical practice when symptoms persist despite therapy or when treatment
      discontinuation is being considered. Conversely, in patients whose clinical
      remission is not associated with mucosal healing, intensification of treatment is
      not currently recommended because of lack of evidence.

PMID- 22406344
TI  - Evidence of West Nile virus lineage 2 circulation in Northern Italy.
AB  - A West Nile virus (WNV) strain belonging to lineage 2 was for the first time
      detected in two pools of Culex pipiens collected in the province of Udine and in
      tissues of a wild collared dove (Streptopelia decaocto) found dead in the
      province of Treviso, in North East of Italy. It was molecularly identified by
      group and WNV lineage specific RT-PCRs and characterized by partial sequencing of
      the NS3 and NS5 genes. When compared with the sequences of same fragments of NS3
      and NS5 of the WNV lineage 2 strain isolated from birds of prey in Hungary
      (2004), the phylogenetic analysis of these sequences revealed 100% and 99%
      similarity, respectively. As the Hungarian strain, the NS3 selected sequence
      differed from the 2010 Greek isolate by one amino-acid located at 249 site which
      is the site involved in genetic modulation of WNV pathogenicity. The Italian and
      Hungarian strains have histidine rather than proline at this site. The presence
      of a lineage 2 strain in regions where the lineage 1 strain is still circulating,
      creates a new scenario with unpredictable consequences. In this situation
      comprehensive investigations on the occurrence, ecology, and epidemiology of
      these different WNV strains circulating in Italy become the highest priority.

PMID- 22406345
TI  - ORF1 but not ORF2 dependent differences are important for in vitro replication of
      PCV2 in porcine alveolar macrophages singularly or coinfected with PRRSV.
AB  - The objective of this study was to investigate cytokine expression and in vitro
      replication of porcine circovirus type 2 (PCV2) and porcine reproductive and
      respiratory syndrome virus (PRRSV) in pulmonary alveolar macrophages (PAMs)
      emphasizing PCV2 open-reading frame (ORF) origin (PCV2a or PCV2b) and PRRSV
      strain. Chimeric PCV2 viruses composed of different combinations of ORF1 and ORF2
      of PCV2a or PCV2b (chimera PCV2a-2b and chimera PCV2b-2a) were constructed and
      five different PRRSV isolates were utilized: Type 1 (SD 01-08) or type 2
      (NC16845b, VR-2332, MN-184, JA-142). PAMs were infected singularly or with
      combinations of PCV2b, PCV2a, chimera PCV2a-2b, and chimera PCV2b-2a, and one of
      the five PRRSV isolates. Real-time PCR was used to test PAMs (PCV2 mRNA) and
      supernatants (PRRSV RNA, PCV2 DNA, PCV2 mRNA) harvested at 24, 48, 72 and 96h
      post inoculation (hpi). Levels of IFN-gamma, TNF-alpha and IL-10 were determined
      by quantitative ELISAs. PCV2 replication in PAMs was limited to groups inoculated
      with PCV2 strains containing ORF1 of PCV2a (PCV2a, chimera PCV2a-2b).
      Furthermore, in supernatants, PCV2 mRNA was only detected in groups coinfected
      with PRRSV regardless of strain at 48hpi supporting an enhancing effect of PRRSV
      on PCV2 infection. Changes in cytokine levels were minimal and associated with
      PRRSV strain for TNF-alpha. In summary, in vitro differences in PCV2 replication
      in PAMs inoculated with different PCV2-PRRSV combinations were independent of
      PCV2 ORF2 origin with minimal effects of concurrent PRRSV infection perhaps
      indicating that PCV2-specific changes in ORF1 may be more important than those in
      ORF2.

PMID- 22406346
TI  - Effect of porcine circovirus type 2a or 2b on infection kinetics and
      pathogenicity of two genetically divergent strains of porcine reproductive and
      respiratory syndrome virus in the conventional pig model.
AB  - To determine differences in infection kinetics of two temporally and genetically
      different type 2 porcine reproductive and respiratory syndrome virus (PRRSV)
      isolates in vivo with and without concurrent porcine circovirus (PCV) type 2a or
      2b infection, 62 pigs were randomly assigned to one of seven groups: negative
      controls (n=8); pigs coinfected with a 1992 PRRSV strain (VR-2385) and PCV2a (CoI
      92-2a; n=9), pigs coinfected with VR-2385 and PCV2b (CoI-92-2b; n=9), pigs
      coinfected with a 2006 PRRSV strain (NC16845b) and PCV2a (CoI-06-2a; n=9), pigs
      coinfected with NC16845b and PCV2b (CoI-06-2b; n=9), pigs infected with VR-2385
      (n=9), and pigs infected with NC16845b (n=9). Blood samples were collected before
      inoculation and at day post-inoculation (dpi) 3, 6, 9 and 12 and tested for the
      presence of PRRSV antibody and RNA, PCV2 antibody and DNA, complete blood counts,
      and interferon gamma (IFN-gamma) levels. Regardless of concurrent PCV2 infection,
      VR-2385 initially replicated at higher levels and reached peak replication levels
      at dpi 6. Pigs infected with VR-2385 had significantly higher amounts of viral
      RNA in serum on both dpi 3 and dpi 6, compared to pigs infected with NC16845b.
      The peak of NC16845b virus replication occurred between dpi 9 and dpi 12 and was
      associated with a delayed anti-PRRSV antibody response in these pigs. PCV2
      coinfection resulted in significantly more severe macroscopic and microscopic
      lung lesions and a stronger anti-PRRSV IgG response compared to pigs infected
      with PRRSV alone. This work further emphasizes in vivo replication differences
      among PRRSV strains and the importance of coinfecting pathogens.

PMID- 22406347
TI  - The case of the forgotten toothbrush.
AB  - INTRODUCTION: Although foreign body ingestion is relatively common, toothbrush
      swallowing is rare. A diagnosis of small-bowel perforation, caused by a sharp or
      pointed foreign body, is rarely made preoperatively because the clinical symptoms
      are usually nonspecific and can mimic other surgical conditions, such as
      appendicitis and diverticulitis. PRESENTATION OF CASE: We report a case of a
      swallowed toothbrush which passed past the pylorus and perforated the terminal
      ileum. The patient however presented with a fluctuant mass in the left iliac
      fossa, pyrexia and generalised tenderness mimicking a diverticular abscess.
      DISCUSSION: Ingestion of a foreign body is commonly encountered in the clinic
      among children, adults with intellectual impairment, psychiatric illness or
      alcoholism, and dental prosthetic-wearing elderly subjects. However, toothbrush
      swallowing is rare, with only approximately 40 reported cases. CONCLUSION: Bowel
      perforation by foreign bodies can mimic acute appendicitis and should be
      considered in differential diagnoses. Clinically, patients often do not recall
      ingesting the foreign body, which makes the clinical diagnosis more challenging,
      and a correct diagnosis is frequently delayed. Several radiological
      investigations, such as small-bowel series, ultrasonography, and computed
      tomography scans, may lead to the correct diagnosis, but in most patients, the
      diagnosis is not confirmed until the surgical intervention has been performed.

PMID- 22406348
TI  - The gut-brain dopamine axis: a regulatory system for caloric intake.
AB  - Post-ingestive factors are known to strongly modulate feeding behavior by
      providing feedback signals to the central nervous system on the current
      physiological state of the organism. Of particular interest is the identification
      of the physiological pathways that permit the brain to sense post-ingestive
      signals. We will review recent evidence supporting the concept that direct
      stimulation of the gastrointestinal tract with nutrients induces release of the
      catecholamine neurotransmitter dopamine. In addition, changes in dopamine efflux
      produced by direct stimulation of the gastrointestinal tract were found to
      reflect the caloric load of the infusates, suggesting that dopamine signaling may
      function as a central caloric sensor that mediates adjustments in intake
      according to the caloric density of a meal. Consistent with the above, blockade
      of dopamine signaling disrupts flavor-nutrient associations and impairs the
      regulatory capacity to maintain constant caloric intake during intra-gastric
      feeding. Future research must determine the exact pathways linking gut nutrient
      administration to dopamine efflux. Current evidence points to parallel
      contributions by pre- and post-absorptive pathways, indicating that dopamine
      systems constitute a site of convergence through which distinct physiological
      signals can exert control over ingestive behaviors.

PMID- 22406349
TI  - LC-ESI-MS/MS determination of in vivo metabolites of almotriptan in rat plasma,
      urine and feces: application to pharmacokinetics.
AB  - A highly sensitive and specific liquid chromatography-electrospray ionization
      tandem mass spectrometric (LC-ESI-MS/MS) method for investigating the in vivo
      metabolites of almotriptan in rat plasma, feces and urine was developed.
      Chromatographic separation was achieved on a Lichrospher RP-18 column (250 mm *
      4.6 mm, 5 MUm), using 20mM ammonium acetate (pH 3.5) and acetonitrile (60:40,
      v/v) as a mobile phase at 25 degrees C. MS/MS detection was performed by positive
      ion electrospray ionization using target ions at m/z 336 [M+H]+, m/z 368 and m/z
      282 [M+H]+ for almotriptan and its two metabolites, respectively. Two metabolites
      viz., gamma-aminobutyric acid and sulfonamide were detected in plasma as well as
      feces after 24 h of oral administration of almotriptan, while only gamma
      aminobutyric acid was found in urine. The method was sensitive with a lower limit
      of quantification of 1.43 ng/mL and linear over the range of 1.43-5000 ng/mL in
      plasma. The method was validated and successfully applied to a pharmacokinetic
      study of almotriptan in rat plasma using sumatriptan as an internal standard. The
      peak plasma concentration (C(max)) after 0.3h of 5mg/kg oral dose of almotriptan
      was determined to be 69.85 ng/mL.

PMID- 22406350
TI  - Comparison of IMAC and MOAC for phosphopeptide enrichment by column
      chromatography.
AB  - Automated phosphopeptide enrichment prior to MS analysis by means of Immobilized
      Metal Affinity Chromatography (IMAC) and Metal Oxide Affinity Chromatography
      (MOAC) has been probed with packed columns. We compared POROS-Fe3+ and TiO2
      (respectively IMAC and MOAC media), using a simple mixture of peptides from
      casein-albumin and a complex mixture of peptides isolated from mouse liver. With
      theses samples, selectivity of POROS-Fe3+ and TiO2 were pH dependant. In the case
      of liver extract, selectivity increased from 12-18% to 58-60% when loading buffer
      contained 0.1 M acetic acid or 0.1 M trifluoroacetic acid, respectively. However,
      with POROS-Fe3+ column, the number of identifications decreased from 356
      phosphopeptides with 0.1 M acetic acid to 119 phosphopeptides with 0.1 M TFA.
      This decrease of binding capacity of POROS-Fe3+ was associated with strong Fe3+
      leaching. Furthermore, repetitive use of IMAC-Fe3+ with the 0.5 M NH4OH solution
      required for phosphopeptide elution induced Fe2O3 accumulation in the column. By
      comparison, MOAC columns packed with TiO2 support do not present any problem of
      stability in the same conditions and provide a reliable solution for packed
      column phosphopeptide enrichment.

PMID- 22406351
TI  - Thinking ahead or not? Natural aging and anticipation during reading.
AB  - Despite growing evidence of young adults neurally pre-activating word features
      during sentence comprehension, less clear is the degree to which this generalizes
      to older adults. Using ERPs, we tested for linguistic prediction in younger and
      older readers by means of indefinite articles (a's and an's) preceding more and
      less probable noun continuations. Although both groups exhibited cloze
      probability-graded noun N400s, only the young showed significant article effects,
      indicating probabilistic sensitivity to the phonology of anticipated upcoming
      nouns. Additionally, both age groups exhibited prolonged increased frontal
      positivities to less probable nouns, although in older adults this effect was
      prominent only in a subset with high verbal fluency (VF). This ERP positivity to
      contextual constraint violations offers additional support for prediction in the
      young. For high VF older adults, the positivity may indicate they, too, engage in
      some form of linguistic pre-processing when implicitly cued, as may have occurred
      via the articles.

PMID- 22406352
TI  - Terminal galactosylation of glycoconjugates in Plasmodium falciparum asexual
      blood stages and Trypanosoma brucei bloodstream trypomastigotes.
AB  - There is definitive biochemical evidence for the presence of terminal alpha
      galactosyl residues (alpha-gal) in the N-linked oligosaccharides and
      glycophosphatidylinositol anchors (GPI anchors) of the variant surface
      glycoprotein of Trypanosoma brucei bloodstream trypomastigotes. Indirect evidence
      also exists for alpha-gal in Plasmodium falciparum asexual blood stage
      glycoproteins and glycolipids. The occurrence of alpha-gal in glycoproteins and
      glycolipids of T. brucei bloodstream trypomastigotes and P. falciparum late
      asexual blood stages was investigated by the binding of alpha-gal-specific
      Bandeirea simplicifolia B4 lectin 1 (BSB4), incorporation of [(3)H]galactose from
      UDP-[(3)H]galactose into glycoproteins and glycolipids in microsomes in vitro,
      and bioinformatic searches for galactosyl-transferase coding sequences. The
      findings confirm the presence of alpha-gal in a spectrum of T. brucei bloodstream
      trypomastigote glycoproteins and glycolipids and indicate its relative absence
      from P. falciparum asexual blood stage glycoconjugates.

PMID- 22406353
TI  - Feather pillows and the increased risk of childhood asthma.

PMID- 22406354
TI  - Correlates of perceptual awareness in human primary auditory cortex revealed by
      an informational masking experiment.
AB  - The presence of an auditory event may remain undetected in crowded environments,
      even when it is well above the sensory threshold. This effect, commonly known as
      informational masking, allows for isolating neural activity related to perceptual
      awareness, by comparing repetitions of the same physical stimulus where the
      target is either detected or not. Evidence from magnetoencephalography (MEG)
      suggests that auditory-cortex activity in the latency range 50-250 ms is closely
      coupled with perceptual awareness. Here, BOLD fMRI and MEG were combined to
      investigate at which stage in the auditory cortex neural correlates of conscious
      auditory perception can be observed. Participants were asked to indicate the
      perception of a regularly repeating target tone, embedded within a random multi
      tone masking background. Results revealed widespread activation within the
      auditory cortex for detected target tones, which was delayed but otherwise
      similar to the activation of an unmasked control stimulus. The contrast of
      detected versus undetected targets revealed activity confined to medial Heschl's
      gyrus, where the primary auditory cortex is located. These results suggest that
      activity related to conscious perception involves the primary auditory cortex and
      is not restricted to activity in secondary areas.

PMID- 22406357
TI  - The neural correlates of subjective pleasantness.
AB  - Processing of subjective pleasantness is essential in daily life decision making,
      particularly in the context of cognitive and environmental factors. Pleasure is
      mediated by a neural network and this network has been suggested to be the
      biological basis of pleasure including a whole range of different modalities and
      domains of pleasantness. This quantitative meta-analysis of brain imaging data
      focuses on studies 1) based on correlations between self-reported judgements of
      pleasantness and brain regions and investigates whether 2) immediate (during
      scanning) versus subsequent judgements (after scanning) differ in brain activity.
      We investigated concurrence across 40 studies reporting brain regions correlated
      with self-reported judgements of subjective pleasantness (attractiveness, liking
      or beauty) by means of activation likelihood estimation (ALE). Positive
      correlates of subjective pleasantness were found in mOFC, ventromedial prefrontal
      cortex, left ventral striatum, pregenual cortex, right cerebellum, left thalamus
      and the mid cingulate cortex. Negative correlates were found in left precentral
      gyrus, right cerebellum and right inferior frontal gyrus. A comparison of studies
      with subjective pleasantness judgement during or after scanning revealed no
      significant differences in brain activation. We conclude that subjective
      pleasantness judgements are directly related to brain regions that have been
      described as part of the reward circuitry (mOFC, ventral striatum). The results
      suggest that the evaluation of likability or pleasure is an automatic process and
      that it is neither elicited nor enhanced by instructions to report the outcome of
      these judgements.

PMID- 22406355
TI  - Is there a path beyond BOLD? Molecular imaging of brain function.
AB  - The dependence of BOLD on neuro-vascular coupling leaves it many biological steps
      removed from direct monitoring of neural function. MRI based approaches have been
      developed aimed at reporting more directly on brain function. These include:
      manganese enhanced MRI as a surrogate for calcium ion influx; agents responsive
      to calcium concentrations; approaches to measure membrane potential; agents to
      measure neurotransmitters; and strategies to measure gene expression. This work
      has led to clever design of molecular imaging tools and many contributions to
      studies of brain function in animal models. However, a robust approach that has
      potential to get MRI closer to neurons in the human brain has not yet emerged.

PMID- 22406356
TI  - Impact of L-DOPA treatment on regional cerebral blood flow and metabolism in the
      basal ganglia in a rat model of Parkinson's disease.
AB  - Large increases in regional cerebral blood flow (rCBF) have been measured in
      patients with Parkinson's disease (PD) following the administration of L-DOPA,
      but the underlying mechanisms have remained unknown. In this study, rats with
      unilateral 6-hydroxydopamine (6-OHDA) lesions were used to compare patterns of
      rCBF and regional cerebral glucose utilisation (rCGU) in chronically L-DOPA
      treated subjects following a final injection of L-DOPA or saline. The same animal
      model was used to the leakage of a blood-brain barrier (BBB) tracer molecule at
      60 min vs. 24h following the last L-DOPA injection of a chronic treatment. All
      the parameters under investigation were examined with brain autoradiography
      following intravenous injections of specific radiotracers in awake animals ([14C]
      iodoantipyrine for rCBF, [14C]-2-deoxyglucose for rCGU, and [14C]-alpha
      aminoisobutyric acid for BBB leakage). Significant changes in rCBF and rCGU on
      the side ipsilateral to the 6-OHDA lesion relative to the non-lesioned side were
      seen at 60 min ("ON") but not 24h ("OFF") following L-DOPA administration. These
      changes were not seen in sham-operated rats. In the output nuclei of the basal
      ganglia (the entopeduncular nucleus and the substantia nigra pars reticulata)
      both rCBF and rCGU were elevated both in acutely L-DOPA-treated rats and
      chronically L-DOPA-treated rats displaying dyskinesia, but did not change
      significantly in chronically L-DOPA-treated non-dyskinetic cases. Acutely and
      chronically L-DOPA-treated rats with dyskinesia exhibited increases in rCBF "ON L
      DOPA" also in the motor cortex, the striatum, and the globus pallidus, but the
      corresponding changes in rCGU did not show the same direction, magnitude, and/or
      relative group differences. The uptake of a BBB tracer (studied in the striatum
      and the substantia nigra reticulata in chronically L-DOPA treated rats) was
      significantly higher ON vs. OFF L-DOPA. The present results are the first to show
      that the administration of L-DOPA is followed by transient and robust increases
      in rCBF in the dopamine-denervated basal ganglia. This effect occurs already upon
      acute L-DOPA treatment and persists upon repeated drug administration in animals
      that develop dyskinesia. Increases in rCBF ON L-DOPA are not necessarily
      accompanied by enhanced glucose utilisation in the affected regions, pointing to
      altered mechanisms of neurovascular coupling. Finally, our results show that
      increases in rCBF ON L-DOPA may be accompanied by BBB hyperpermeability in the
      most affected regions.

PMID- 22406358
TI  - From N400 to N300: variations in the timing of semantic processing with
      repetition.
AB  - The present study aimed to explore the variations of semantic processing
      according to the number of target words (i.e., 4, 12 and 24) and according to the
      number of repetitions (i.e, 1 to 15). The number of targets had no impact on the
      N400 brain potential, the index of semantic processing, nor on the late positive
      component (LPC), an index of episodic encoding and retrieval. Analyses of the
      effects of the number of repetitions showed that the duration of semantic
      processes--assessed by measuring N400 latency--was linearly shortened along
      repetitions while their extent--as indexed by N400 amplitude--remained constant
      after the second presentation. In contrast, the extent of episodic processes--as
      indexed by LPC amplitude--was found to increase linearly with repetition. By
      showing that N400 latency may be much less stable than previously thought, these
      results bring new constraints on the functional correlates of this key stage in
      the processing of semantic information. They also suggest that semantic processes
      can be studied at high repetition rates whatever the number of target stimuli.
      Finally, our findings show that each episode of prior presentation has an impact
      on the late processing of a stimulus despite the absence of an explicit memory
      task.

PMID- 22406359
TI  - Role of cyclin D1 amplification and expression in vulvar carcinomas.
AB  - Cyclin D1 (CCND1) belongs to the family of D-type cyclins involved in cell cycle
      progression, transcriptional regulation, and cell migration. CCND1 was found to
      be amplified and overexpressed in a variety of cancers, including some vulvar
      carcinoma cell lines. To determine the relationship of CCND1 copy number changes
      and CCND1 protein expression with clinicopathologic features and prognosis, 183
      vulvar carcinomas were analyzed on a tissue microarray. Amplification was
      observed in 32 (22.4%) vulvar cancer specimens and was statistically related to
      the presence of regional lymph node metastases (P < .001). Detectable CCND1
      expression was found in 139 (83.2%) of vulvar carcinomas, and 76 (45.5%)
      exhibited a moderate or strong expression. Increased levels of CCND1 expression
      were significantly related to higher patient age (P = .013), positive pN category
      (P = .004), and negative human papillomavirus status (P < .001). Basaloid as well
      as verrucous, warty-type, and mixed vulvar carcinomas showed lower CCND1
      expression levels than keratinizing or nonkeratinizing tumors (P < .001 and P =
      .032, respectively). Elevated CCND1 expression levels and amplification of the
      CCND1 gene were closely connected in the present analysis (P < .001). Patient
      prognosis was independent from CCND1 amplification status and expression level (P
      = .57 each). In conclusion, CCND1 is amplified and overexpressed in a substantial
      proportion of vulvar carcinomas and associated with the occurrence of
      locoregional lymph node metastases, especially in human papillomavirus-negative
      tumors.

PMID- 22406360
TI  - Identification of biomarkers to distinguish clear cell sarcoma from malignant
      melanoma.
AB  - Clear cell sarcoma is a rare and malignant soft tissue tumor that shows
      phenotypic and immunohistochemical overlap with cutaneous malignant melanoma;
      identification of biomarkers that differentiate clear cell sarcoma from malignant
      melanoma is therefore needed. In this study, we performed mutation analysis of
      BRAF and NRAS, investigated the EWSR1 gene rearrangement and evaluated the
      protein expression of insulin-like growth factor 2 and insulin-like growth factor
      1R in 31 cases of malignant melanoma and 16 cases of clear cell sarcoma. By
      direct sequencing and high-resolution melting analysis, we identified BRAF and
      NRAS mutations in 51.6% and 12.9% of malignant melanoma cases, respectively,
      while none of clear cell sarcoma harbored BRAF or NRAS mutations. Fluorescence in
      situ hybridization showed that 78.6% of clear cell sarcoma exhibited the
      t(12;22)(q13;q12) translocation. The presence of type 1, 2, and 3 EWSR1/ATF1
      fusion gene transcripts was confirmed by reverse transcriptase polymerase chain
      reaction analysis, but type 4 and EWSR1/CREB1 fusion gene transcripts were not
      found. No fusion transcript could be detected in any of the malignant melanoma
      cases. Additionally, immunohistochemistry showed that the majority of clear cell
      sarcoma and malignant melanoma had insulin-like growth factor 2 and insulin-like
      growth factor receptor 1 expression; however the expression of insulin-like
      growth factor 1R was significantly higher in clear cell sarcoma compared to
      melanoma (p = .006). Our results suggest that the combination of BRAF and NRAS
      mutation analysis with fusion gene detection contributes to diagnosis of
      malignant melanoma and clear cell sarcoma, and that insulin-like growth factor 1R
      might be a novel target for the treatment of these two malignancies.

PMID- 22406362
TI  - Developments in the assessment of venous invasion in colorectal cancer:
      implications for future practice and patient outcome.
AB  - Venous invasion, or "large vessel" invasion, is a known independent prognostic
      indicator of distant recurrence and survival in colorectal cancer. Accurate
      assessment of venous invasion is of particular importance in stage II disease
      because it may influence the decision to administer adjuvant therapy. Venous
      invasion is widely believed to be an underreported finding with significant
      variability in its reported incidence. In the most recent College of American
      Pathologists' cancer reporting protocol, venous invasion is not recorded
      separately from lymphovascular, or "small vessel" invasion, which may not be
      appropriate because these features confer differing prognostic information. The
      presence of extramural venous invasion is strongly predictive of adverse outcome,
      although the prognostic significance of intramural venous invasion remains
      unknown. There are no formal guidelines regarding the pathologic assessment of
      venous invasion or the application of specific reporting criteria. The routine
      use of an elastic stain results in an almost 3-fold increase in the venous
      invasion detection rate when compared with a standard hematoxylin and eosin stain
      and may be a cost-effective means of increasing the diagnostic yield of venous
      invasion. The development of high-resolution magnetic resonance imaging, where
      extramural venous invasion can be detected preoperatively, may also influence the
      manner in which pathologists process specimens. This review focuses on recent
      developments in the assessment of venous invasion and highlights their potential
      impact on future practice.

PMID- 22406361
TI  - The novel monoclonal antibody HPC2 and N-cadherin distinguish pancreatic ductal
      adenocarcinoma from cholangiocarcinoma.
AB  - Metastatic pancreatic ductal adenocarcinoma and primary cholangiocarcinoma are
      morphologically very similar and, therefore, challenging to distinguish in liver
      biopsies. The distinction is important because surgical management and prognosis
      differ significantly. Several immunohistochemical markers have been evaluated to
      aid this diagnosis, but aside from N-cadherin, which labels cholangiocarcinoma,
      few provide the combination of good sensitivity and specificity. Our laboratory
      recently developed the novel monoclonal antibody human pancreatic cancer fusion
      #2 (HPC2) that recognizes pancreatic cancer. We hypothesized that the combination
      of our new marker and N-cadherin can assist in distinguishing metastatic
      pancreatic cancer from cholangiocarcinoma. We immunostained resections of 60
      pancreatic ductal adenocarcinomas and 31 cholangiocarcinomas for the HPC2 and N
      cadherin antigens. We also stained 24 gallbladder adenocarcinomas, 11 ampullary
      adenocarcinomas, and 10 metastatic colonic adenocarcinomas to the liver. Sections
      were independently scored by 2 pathologists with good agreement using both
      markers (kappa statistics, 0.62-0.64; P < .0001). HPC2 was observed in 80% of
      pancreatic cancers (48/60), 82% of ampullary (9/11), and 32% (10/31) of
      cholangiocarcinomas. N-cadherin stained 27% (16/60) of the pancreas cases and 58%
      (18/31) of the cholangiocarcinomas. Gallbladder and colon cancers were usually
      double negative (18/24 and 8/10, respectively). Each marker provided significant
      likelihood ratios to separate pancreatic cancer (HPC2, 2.48 [1.46-4.19]; P <
      .0001) from cholangiocarcinoma (N-cadherin, 2.17 [1.3-3.64]; P < .01). The
      combination of both markers provided even better specificity and positive
      likelihood ratios. We conclude that HPC2 and N-cadherin significantly improve
      accurate classification of pancreatic cancer and cholangiocarcinoma.

PMID- 22406364
TI  - Cytokeratin-positive epithelioid angiosarcoma presenting in the tonsil: a
      diagnostic challenge.
AB  - Primary oral cavity sarcomas are exceedingly rare and may pose a great diagnostic
      challenge. A 71-year-old woman without history of malignancy or radiation to the
      head and neck presented with an antibiotic-refractory diffuse painful swelling of
      the right tonsil necessitating tonsillectomy. Histologic evaluation revealed
      subtotal replacement of the right tonsil by a high-grade epithelioid neoplasm
      displaying extensive ulceration, necrosis, and primitive vasoformation.
      Immunohistochemistry showed strong/diffuse expression of pancytokeratin
      antibodies KL-1 and Lu5, cytokeratin 8, cytokeratin 18, cytokeratin 19, vimentin,
      CD31, ERG, and Freund leukemia integration site 1 (FLI-1). High-molecular-weight
      cytokeratins (cytokeratin 5, 34beta12), cytokeratin 7, cytokeratin 13, and
      cytokeratin 20 were not expressed. Within months, the patient underwent surgical
      resection of multiple bleeding intraoral and gastrointestinal metastases. She is
      currently alive with disease 9 months from diagnosis. To our knowledge, this case
      represents the first well-documented primary epithelioid angiosarcoma of the
      tonsil. The strong cytokeratin expression in epithelioid angiosarcomas represents
      a diagnostic pitfall. Thus, awareness of this rare and highly aggressive neoplasm
      is necessary for distinguishing it from poorly differentiated and acantholytic
      squamous cell carcinoma and diffuse large cell lymphoma.

PMID- 22406363
TI  - High epidermal growth factor receptor immunohistochemical expression in
      urothelial carcinoma of the bladder is not associated with EGFR mutations in
      exons 19 and 21: a study using formalin-fixed, paraffin-embedded archival
      tissues.
AB  - Epidermal growth factor receptor (EGFR) is a member of the erbB tyrosine kinase
      family reported to be overexpressed in a variety of solid malignancies. Mutations
      in exons 19 to 21 of the tyrosine kinase domain have been detected in a subset of
      these tumors and its presence associated with a better response to EGFR
      inhibitors. Several clinical trials are currently underway to evaluate the
      performance of such drugs in patients with bladder cancer, but data on EGFR
      mutation status are limited. The current study assesses EGFR immunohistochemical
      expression and the presence of mutations in exons 19 and 21 by polymerase chain
      reaction in 19 bladder urothelial carcinomas from formalin-fixed, paraffin
      embedded tissues. Representative paraffin sections were microdissected for DNA
      extraction using a pinpoint isolation system. Parallel sections were
      immunostained using a monoclonal anti-EGFR antibody. No mutations in exons 19 and
      21 of EGFR were identified in any of the cases. Immunohistochemical EGFR
      positivity was observed in 14 of 19 cases. In summary, we found EGFR protein
      expression in 74% of urothelial carcinomas, but we failed to detect EGFR
      mutations at exons 19 to 21, suggesting that EGFR overexpression is not related
      to the presence of mutations in the tyrosine kinase domain of the gene. Mutation
      analysis of EGFR exons 19 and 21 is feasible in microdissected paraffin sections
      from archival tissues. Immunohistochemical expression of EGFR may not be useful
      to predict therapeutic response to EGFR inhibitors in patients with urothelial
      carcinomas. To explain EGFR immunohistochemical overexpression, other mechanisms
      besides mutations in the EGFR kinase domain should be investigated in future
      studies.

PMID- 22406365
TI  - Neonatal Fc receptor stimulation induces ubiquitin c-terminal hydrolase-1
      overexpression in podocytes through activation of p38 mitogen-activated protein
      kinase.
AB  - Ubiquitin c-terminal hydrolase-1 is overexpressed in renal podocytes in some
      immune complex-mediated glomerulonephritides, an effect closely related to
      extensive podocyte injury. Neonatal Fc receptor is newly recognized to be present
      on human renal podocytes. It is presumed that neonatal Fc receptor serves as a
      sensor for immune stimulation transduction and is involved in the pathogenesis of
      podocyte injury. In our current study, we found that neonatal Fc receptor was
      constitutively expressed in normal podocytes and up-regulated by immune
      stimulation induced by antithymocyte serum. An increase in neonatal Fc receptor
      expression was observed in human podocytes within diseased glomeruli in 97 cases
      of various glomerulonephritides. The expression percentage was significantly
      higher in immune-mediated disease, including membranous nephropathy (46.7%),
      immunoglobin A nephropathy (66.7%), lupus nephritis (87.5%), and acute
      proliferative glomerulonephritis (100%), than in normal kidney samples (16.7%) (P
      < .05), whereas there was no significant difference between minimal-change
      disease and normal kidney. Further study showed that neonatal Fc receptor up
      regulated the expression of ubiquitin c-terminal hydrolase-1 via activation of
      p38 in podocytes subjected to immune stimulation in vitro. These data suggest
      that neonatal Fc receptor acts as an immune sensor that evokes an inflammatory
      response, which may lead to functional and morphological changes in podocytes in
      glomerulonephritides.

PMID- 22406366
TI  - Pseudomyxoma peritonei (mucinous carcinoma peritonei) preceded by intraductal
      papillary neoplasm of the bile duct.
AB  - Pseudomyxoma peritonei (mucinous carcinoma peritonei) is a rare clinical disease.
      Although most cases derive from appendiceal mucinous tumors, a few are associated
      with pancreatic intraductal papillary mucinous neoplasms. Intraductal papillary
      neoplasms of the bile duct share many similarities with pancreatic intraductal
      papillary mucinous neoplasms and are thought to be their biliary counterparts. We
      report a case of low-grade intraductal papillary neoplasm of the bile duct who
      developed pseudomyxoma peritonei 6 years after surgical treatment of the primary
      biliary tumor. To the best of our knowledge, this is the first case of
      pseudomyxoma peritonei associated with intraductal papillary neoplasm of the bile
      duct. The tumor recurrence in our case may be due to tumor spillage at the time
      of the first surgery, since there is no recurrent biliary tumor in the preserved
      liver lobe. Prevention of spillage of epithelial cell-containing mucin during
      surgical operations is important in treating intraductal papillary neoplasms of
      the bile duct.

PMID- 22406367
TI  - Nuclear factor kappaB predicts poor outcome in patients with hormone-naive
      prostate cancer with high nuclear androgen receptor.
AB  - Despite recent advances in prostate cancer treatments, disease recurrence is
      common and associated with significant morbidity and mortality. The need for more
      effective antitumor agents has led researchers to target signaling pathways that
      drive tumorigenesis by modulating or bypassing androgen receptor signaling-
      attenuation or blockade of which current treatments aim to effect. The
      transcription factor nuclear factor kappaB/p65 has been implicated in prostate
      cancer progression; however, few studies have examined the involvement of nuclear
      factor kappaB in hormone-naive disease. We used immunohistochemistry to
      investigate expression of p65, androgen receptor, Ki-67, and phosphorylation
      status of p65 at serine 536, in 154 tumor samples taken from patients before
      hormone ablation or radical treatment. Nuclear p65 expression was significantly
      associated with disease-specific mortality: P = .005; hazard ratio, 2.2. When
      patients were stratified according to androgen receptor status, this relationship
      was abolished in low androgen receptor-expressing patients and potentiated in
      high androgen receptor-expressing patients: P = .002; hazard ratio, 3.1. Ki-67
      expression was also prognostic of shorter disease-specific mortality: P = .001;
      hazard ratio, 2.3. When the cohort was stratified according to androgen receptor
      status, this relationship held for high androgen receptor expressers but not low
      expressers: P = .0003; hazard ratio, 3.5. Neither androgen receptor nor p65
      phosphorylated at S536 were significantly prognostic when considered
      individually. These data suggest that future prostate cancer treatments that
      target nuclear factor kappaB signaling should be assigned primarily to patients
      with concomitant high nuclear p65 and androgen receptor expression.

PMID- 22406368
TI  - High expression of trimethylated histone H3 lysine 4 is associated with poor
      prognosis in hepatocellular carcinoma.
AB  - Tumor-associated epigenetic alterations including DNA methylation and histone
      modifications are important determinants in the initiation and progression of
      hepatocellular cancer (HCC) and represent promising biomarkers and therapeutic
      targets. Locus-specific trimethylation of histone H3 lysine 4 (H3K4me) is a well
      known modification linked to the enhanced transcriptional expression of many
      genes activated in HCC. Our aim was to assess the cellular expression pattern of
      H3K4me3 in HCC and its association with clinicopathologic variables and outcome.
      Expression of H3K4me3 and the histone methyltransferase (HMT) SET and MYND domain
      containing protein 3 (SMYD3) was studied by Western blotting and
      immunohistochemistry in cell lines and tumor tissue microarray from a well
      characterized series of HCC patients (n = 168). The optimal cut-point of H3K4me3
      expression for prognosis was determined by the X-tile program. The prognostic
      significance was evaluated using Kaplan-Meier survival estimates and log-rank
      tests. Tumor tissue microarray from another independent HCC patients cohort (n =
      147) was used for validation studies. Expression of H3K4me3 and SMYD3 were
      enhanced in HCC cell lines. In tumor specimens, enhanced expression of H3K4me3
      was correlated with reduced overall survival (P < .0001), especially in early
      stage HCC patients (TNM I/II). Furthermore, both univariate and multivariate
      analyses revealed that H3K4me3 level was a significant and independent predictor
      of poor survival (hazard ratio, 3.592; 95% confidence interval, 2.302-5.605). In
      addition, H3K4m3 expression was positively correlated with SMYD3 expression in
      both testing and validation cohorts (P < .0001). In conclusion, H3K4me3 level
      defines unrecognized subsets of HCC patients with distinct epigenetic phenotype
      and clinical outcome and can thus be a novel predictor for poor prognosis of HCC
      patients, especially at TNM I/II stage.

PMID- 22406369
TI  - Frozen section assessment in testicular and paratesticular lesions suspicious for
      malignancy: its role in preventing unnecessary orchiectomy.
AB  - To investigate the role of frozen section assessment in sparing unnecessary
      orchiectomy for suspected lesions, we retrospectively reviewed intraoperative
      testicular and paratesticular frozen section assessments performed at our
      institution between the years 1993 and 2010. Frozen section assessments were
      performed on 45 testicular lesions (age, 5-60 [mean, 32.2] years; lesion size,
      0.5-9.7 [mean, 2.1] cm) and 20 paratesticular lesions (age, 26-76 [mean, 43.5]
      years; lesion size, 0.4-11.0 [mean, 2.8] cm) before the decision to complete
      radical orchiectomy. Benign/malignant frozen section assessment diagnoses were
      reported in 26/19 testicular cases and 17/3 paratesticular cases, respectively.
      Of the 26 benign testicular frozen section assessments, 5 cases resulted in
      orchiectomy, where permanent diagnoses included epidermoid cyst, large cell
      calcifying Sertoli cell tumor, fibrous pseudotumor, abscesses, and sarcoidosis,
      caused by a concern for potential malignancy or questionable viability of the
      testicles. Of the 19 malignant testicular frozen section assessments, orchiectomy
      was performed in 16 cases with germ cell tumor, but not in the remaining 3 cases
      with lymphoma. Of the 17 benign paratesticular frozen section assessments, 2
      cases, both fibrous pseudotumors, resulted in orchiectomy. There were
      statistically significant differences in the size of the testicular (P < .001) or
      paratesticular (P < .001) lesions between benign and malignant frozen section
      assessments. Thus, in 36 (83.7%) of 43 cases with benign frozen section
      assessments, in addition to all 3 cases of lymphoma, orchiectomy was successfully
      avoided. These results suggest that frozen section assessment is useful for
      permitting testicular preservation, especially in men with small, nonpalpable,
      incidentally found masses as well as other benign lesions where a clinical
      diagnosis of malignancy is in doubt.

PMID- 22406370
TI  - CD5-positive mucosa-associated lymphoid tissue (MALT) lymphoma: a
      clinicopathologic study of 14 cases.
AB  - Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT
      lymphoma) is a B-cell neoplasm that is typically CD5 negative. We describe the
      clinicopathologic, immunophenotypic, and cytogenetic features of 14 cases of CD5+
      MALT lymphoma. There were 9 men and 5 women (median age, 68 years; range, 34-87
      years). MALT lymphoma was initially diagnosed in salivary glands (n = 4),
      nasopharynx (n = 2), and 1 case each in conjunctiva, thyroid, stomach, colon,
      skin, lung, kidney, and retroperitoneum. Two patients had localized disease; 9
      had disseminated disease with generalized lymphadenopathy (n = 8), multifocal
      lymphoma (n = 6), or bone marrow involvement (n = 5). No staging information was
      available for the remaining patients. None presented with B symptoms,
      splenomegaly, cytopenias, lymphocytosis, monoclonal gammopathy, or elevated serum
      lactate dehyrogenase. Serum beta2-microglobulin was elevated in 6.
      Morphologically, the neoplasms had features typical of MALT lymphoma being
      composed of small- to medium-sized cells with round to slightly irregular nuclear
      contours and moderate amount of cytoplasm. Lymphoepithelial lesions were noted in
      4 cases. CD5 was positive in all cases by immunohistochemistry (n = 12) and/or
      flow cytometry (n = 11). All cases assessed were negative for cyclin D1 (13/13)
      and CD10 (11/11). Conventional cytogenetics in 7 cases showed trisomy 3 in 3 and
      diploid in 4. With a median follow-up of 71 months (range, 2-131 months), overall
      survival at 5 years was 100%, although 5 patients required chemotherapy. Our
      results show that CD5 expression is rare in MALT lymphoma, and is often
      associated with nongastric disease and an increased tendency to present with
      disseminated disease. Overall survival is excellent with appropriate therapy.

PMID- 22406371
TI  - Cardiac and skeletal myopathy in Fabry disease: a clinicopathologic correlative
      study.
AB  - Skeletal muscle disturbances are commonly reported in patients with Fabry
      disease. Whether they derive from cardiac dysfunction or direct muscle
      involvement is still unclear. Clinical, noninvasive, and invasive cardiac and
      muscle studies, including an endomyocardial and muscle biopsy, were obtained in
      12 patients (mean age, 42.1 +/- 12.6 years; range, 24-58 years) with Fabry
      disease. In the youngest patients (group A, 4 men aged <35 years), results of
      cardiac and skeletal noninvasive studies were normal, except for reduced
      velocities in tissue Doppler imaging. Histologic examination indicated that
      muscle myocytes were unaffected, whereas muscle vessels showed the presence of
      mild glycosphingolipid accumulation in endothelial and smooth muscle cells. In
      the heart, cardiomyocytes and endothelial and smooth muscle cells of intramural
      cardiac vessels were involved by the disease. The oldest patients (group B, 6 men
      and 2 women aged >35 years) showed ultrasound muscle disarray and
      electromyography signs of myopathy, increased left ventricular mass, and normal
      cardiac function. Histologic examination showed that muscle myocytes contained
      mild glycosphingolipid accumulation compared with severe engulfment of
      cardiomyocytes. Moreover, similar infiltration of myocardial and muscle
      intramural vessels, causing lumen narrowing and fibrofatty tissue replacement,
      was observed. Direct muscle involvement occurs in patients with Fabry disease. It
      is milder and delayed compared with that in the heart. The difference in organ
      function and the need of residual alpha-galactosidase A activity are the likely
      causes.

PMID- 22406372
TI  - Predominance of TH2 cells and plasma cells in polyoma virus nephropathy: a role
      for humoral immunity?
AB  - The differential diagnosis of T cell-mediated rejection (TCMR) and BK-virus
      nephropathy (BKVN) in renal transplant biopsies is notoriously difficult.
      Therefore, attempts were made to differentiate between the two by characterizing
      the immune cell infiltrate. Using immunohistochemistry, the distribution of
      immune cell (sub)populations such as CD4(+) T helper (TH), TH1, TH2, CD8(+)
      cytotoxic T cells, regulatory T cells, B cells, plasma cells and follicular
      dendritic cells was determined in a total of 38 renal biopsy specimens. In
      addition, the expression of the HLA class I antigen presentation machinery (APM)
      components was investigated. In general, the frequency of T cells was higher than
      B cells, and TH cells outnumbered cytotoxic T cells with a predominance of TH2
      over TH1 cells. In BKVN, a significantly higher number of plasma cells was
      observed (P = .028), and interstitial fibrosis and tubular atrophy was more
      pronounced in BKVN (P = .007) compared to TCMR. The expression of components of
      the HLA class I APM was not affected by the infection with BK virus compared to
      TCMR. These findings indicate a TH2 shift in renal transplants in the context of
      alloreactive and virus-induced inflammation maybe as a consequence of
      immunosuppression, which usually targets T cell reaction. The predominance of
      plasma cells might underline an important role of humoral immunity in BKVN.
      Moreover, BK virus does not seem to modulate the expression of HLA class I APM as
      a strategy of immune evasion.

PMID- 22406373
TI  - Factors that impact turnaround time of surgical pathology specimens in an
      academic institution.
AB  - Turnaround time of laboratory results is important for customer satisfaction. The
      College of American Pathologists' checklist requires an analytic turnaround time
      of 2 days or less for most routine cases and lets every hospital define what a
      routine specimen is. The objective of this study was to analyze which factors
      impact turnaround time of nonbiopsy surgical pathology specimens. We calculated
      the turnaround time from receipt to verification of results (adjusted for
      weekends and holidays) for all nonbiopsy surgical specimens during a 2-week
      period. Factors studied included tissue type, number of slides per case,
      decalcification, immunohistochemistry, consultations with other pathologists, and
      diagnosis. Univariate and multivariate analyses were performed. A total of 713
      specimens were analyzed, 551 (77%) were verified within 2 days and 162 (23%) in 3
      days or more. Lung, gastrointestinal, breast, and genitourinary specimens showed
      the highest percentage of cases being signed out in over 3 days. Diagnosis of
      malignancy (including staging of the neoplasia), consultation with other
      pathologists, having had a frozen section, and use of immunohistochemical stains
      were significantly associated with increased turnaround time in univariate
      analysis. Decalcification was not associated with increased turnaround time. In
      multivariate analysis, consultation with other pathologists, use of
      immunohistochemistry, diagnosis of malignancy, and the number of slides studied
      continued to be significantly associated with prolonged turnaround time. Our
      findings suggest that diagnosis of malignancy is central to significantly
      prolonging the turnaround time for surgical pathology specimens, thus
      institutions that serve cancer centers will have longer turnaround time than
      those that do not.

PMID- 22406374
TI  - The healing hand.
AB  - The White Coat Ceremony was introduced by the Arnold P. Gold Foundation
      (http://www.humanism-in
      medicine.org/index.php/programs_grants/gold_foundation_programs/white_coat_ceremo
      y) at the Columbia University College of Physicians and Surgeons in 1993; it was
      established at the University of Iowa in 1995. The Gold Foundation is focused on
      making humanism a much higher priority among physicians, and medical students in
      particular, by reestablishing the notion of the caring physician. It includes
      several core attributes, "I.E., C.A.R.E.S.": Integrity, Excellence, Compassion,
      Altruism, Respect, Empathy, and Service. The White Coat Ceremony is but one of
      several programs run by the Foundation, which includes the Leonard Tow Humanism
      in Medicine Awards and the Gold Humanism Honor Society. In 2008, this journal
      introduced a "Humanities in Pathology" section. Since then, there have been
      relatively few articles published in this vein. What follows is a keynote address
      delivered at the White Coat Ceremony at The University of Iowa on August 19,
      2011. At their core, pathologists are physicians, and we must not lose sight of
      our humanity!

PMID- 22406375
TI  - Chromosomal imbalances in primary hepatic carcinosarcoma.
AB  - Hepatic carcinosarcoma is an infrequent biphasic tumor composed of carcinomatous
      and sarcomatous elements, harboring an unfavorable prognosis. The developmental
      origin of both tumor components and possible molecular genetic mechanisms
      involved in tumorigenesis are still unclear. We report here a case of hepatic
      carcinosarcoma in a 76-year-old patient. The tumor was surgically resected and
      examined histopathologically including immunohistochemical staining. Focal
      hepatocellular differentiation was detected in the carcinomatous components but
      also in the pleomorphic undifferentiated spindle cells. Comparative genomic
      hybridization revealed amp 1q, -4q, -5p14pter, -5q13q31, +6p, -6q, -8p12pter, 
      12p, -13q12q14, -14q in the carcinomatous components, and +6p, -10q25qter, -22q
      in the sarcomatous components. The common +6p harbors the serum response factor
      gene encoding a transcription factor involved in cell proliferation, migration,
      and differentiation, confirmed by immunostaining. Hepatic carcinosarcoma is a
      tumor with biphasic morphology but possible monoclonal origin, showing advanced
      tumor progression in the carcinomatous areas.

PMID- 22406376
TI  - Proteomic analysis of blood cells in fish exposed to chemotherapeutics: evidence
      for long term effects.
AB  - Proteomics technology are increasingly used in ecotoxicological studies to
      characterize and monitor biomarkers of exposure. The present study aims at
      identifying long term effects of malachite green (MG) exposure on the proteome of
      peripheral blood mononuclear cells (PBMC) from the Asian catfish, Pangasianodon
      hypophthalmus. A common (0.1 ppm) concentration for therapeutic treatment was
      applied twice with a 72 h interval. PBMC were collected directly at the end of
      the second bath of MG (T1) and after 1 month of decontamination (T2). Analytical
      2D-DIGE gels were run and a total of 2551+/-364 spots were matched. Among them,
      MG induced significant changes in abundance of 116 spots with no recovery after
      one month of decontamination. Using LC-MS/MS and considering single
      identification per spot, we could identify 25 different proteins. Additionally,
      MG residues were measured in muscle and in blood indicating that leuco-MG has
      almost totally disappeared after one month of decontamination. This work
      highlights long term effects of MG treatment on the PBMC proteome from fish
      intended for human consumption.

PMID- 22406377
TI  - Metformin-mediated Bambi expression in hepatic stellate cells induces prosurvival
      Wnt/beta-catenin signaling.
AB  - AMP-activated protein kinase (AMPK) regulates lipid, cholesterol, and glucose
      metabolism in specialized metabolic tissues, such as muscle, liver, and adipose
      tissue. Agents that activate AMPK, such as metformin and 5-aminoimidazole-4
      carboxamide-1-beta-4-ribofuranoside (AICAR), have beneficial effects on liver
      glucose and lipid metabolism. In addition, AMPK activation in proliferating
      hepatic stellate cells (HSC) induces growth arrest and inhibits hepatic fibrosis.
      As metformin and AICAR act in different ways to achieve their effects, our aim
      was to examine the effects of AMPK activation in quiescent HSCs with these two
      agents on HSC function. We found that phospho-AMPK levels were markedly
      upregulated by both AICAR and metformin in quiescent HSCs. However, although
      AICAR treatment induced cell death, cells treated with metformin did not differ
      from untreated controls. AICAR-mediated HSC cell death was paralleled by loss of
      expression of the TGF-beta decoy receptor Bambi, whereas metformin increased
      Bambi expression. Transfection of siRNA-Bambi into HSCs also induced cell death,
      mimicking the effects of AICAR, whereas overexpression of Bambi partially rescued
      AICAR-treated cells. As Bambi has previously been shown to promote cell survival
      through Wnt/beta-catenin signaling, a reporter incorporating binding sites for a
      downstream target of this pathway was transfected into HSCs and was induced. We
      conclude that although AICAR and metformin both activate AMPK in quiescent HSCs,
      AICAR rapidly induced cell death, whereas metformin-treated cells remained
      viable. The finding that metformin increases Bambi expression and activates
      Wnt/beta-catenin signaling provides a possible mechanistic explanation for this
      observation. These results suggest that AICAR and metformin may confer disease
      specific therapeutic benefits.

PMID- 22406380
TI  - Analysis of PLA2G6 gene mutation in sporadic early-onset parkinsonism patients
      from Chinese population.
AB  - Recent studies have shown that PLA2G6 is a causative gene for PARK14-linked
      autosomal recessive early-onset complicated dystonia-parkinsonism, early-onset
      parkinsonism with frontotemporal dementia and autosomal recessive early-onset
      Parkinsonism without added complicated clinical features. In order to investigate
      the characteristics of PLA2G6 gene mutations in Chinese sporadic early-onset
      parkinsonism (EOP) patients, we performed polymerase chain reaction and DNA
      direct sequencing on a cohort of sporadic EOP patients from Chinese population.
      In this study, we found a novel heterozygous varient (p.G679V). Bioinformatics
      demonstrates that p.G679V exhibits highly conserved residues across species,
      which hints it might be a pathogenic mutation. Our result indicated that PLA2G6
      mutations might not be a main cause of Chinese sporadic EOP.

PMID- 22406378
TI  - Microvesicles shed by oligodendroglioma cells and rheumatoid synovial fibroblasts
      contain aggrecanase activity.
AB  - Membrane microvesicle shedding is an active process and occurs in viable cells
      with no signs of apoptosis or necrosis. We report here that microvesicles shed by
      oligodendroglioma cells contain an 'aggrecanase' activity, cleaving aggrecan at
      sites previously identified as targets for adamalysin metalloproteinases with
      disintegrin and thrombospondin domains (ADAMTSs). Degradation was inhibited by
      EDTA, the metalloproteinase inhibitor GM6001 and by tissue inhibitor of
      metalloproteinases (TIMP)-3, but not by TIMP-1 or TIMP-2. This inhibitor profile
      indicates that the shed microvesicles contain aggrecanolytic ADAMTS(s) or related
      TIMP-3-sensitive metalloproteinase(s). The oligodendroglioma cells were shown to
      express the three most active aggrecanases, namely Adamts1, Adamts4 and Adamts5,
      suggesting that one or more of these enzymes may be responsible for the
      microvesicle activity. Microvesicles shed by rheumatoid synovial fibroblasts
      similarly degraded aggrecan in a TIMP-3-sensitive manner. Our findings raise the
      novel possibility that microvesicles may assist oligodendroglioma and rheumatoid
      synovial fibroblasts to invade through aggrecan-rich extracellular matrices.

PMID- 22406381
TI  - Gene expression and arrhythmic risk.

PMID- 22406382
TI  - Acute hemodynamic response to biventricular pacing in heart failure patients with
      narrow, moderately, and severely prolonged QRS duration.
AB  - BACKGROUND: The efficacy of biventricular (BiV) pacing in patients with a narrow
      or moderately prolonged QRS duration remains questionable. OBJECTIVE: To assess
      the hypothesis that electrical dyssynchrony is required to obtain hemodynamic
      benefit from BiV pacing by investigating the relationship between intrinsic QRS
      duration and hemodynamic response to BiV pacing in a patient population covering
      a broad spectrum of QRS duration. METHODS: Eighty-two consecutive heart failure
      patients underwent cardiac resynchronization therapy implantation irrespective of
      their QRS duration. Thirty-four patients had a narrow QRS duration (<120 ms),
      whereas 11 patients had a moderately prolonged QRS duration (>=120 to <150 ms)
      and 37 patients had a severely prolonged QRS duration (>=150 ms). After
      implantation, invasive left ventricular (LV) dP/dt measurements were compared
      between intrinsic rhythm and simultaneous BiV pacing with an optimized
      atrioventricular delay. RESULTS: A high correlation (r = .65; P < .001) was
      observed between baseline QRS duration and changes in LV dP/dt(max) induced by
      BiV pacing. BiV pacing was ineffective in patients with a narrow QRS duration
      (+0.4% +/- 6.1%; P = ns). No significant increase in LV dP/dt(max) was observed
      in patients with a QRS duration of >=120 to <150 ms (+4.4% +/- 6.9%; P = .06),
      whereas patients with a QRS duration of >=150 ms exhibited a significant increase
      in LV dP/dt(max) (+17.1% +/- 13.4%; P <.001). Only 9% of the patients with a
      narrow QRS duration exhibited a >=10% increase in LV dP/dt(max). CONCLUSIONS:
      Baseline QRS duration is linearly related to acute hemodynamic response to BiV
      pacing. Patients with a narrow QRS duration do not derive hemodynamic
      improvement. This improvement is also limited in patients with a moderately
      prolonged QRS duration, raising questions about the potential clinical benefit of
      this therapy in these patients.

PMID- 22406383
TI  - B groups and gray areas for implantable cardioverter-defibrillators: insights
      from the OMNI registry.

PMID- 22406385
TI  - Hitting a moving target: catheter ablation and respiration.

PMID- 22406384
TI  - Clinical utility of microvolt T-wave alternans testing in identifying patients at
      high or low risk of sudden cardiac death.
AB  - BACKGROUND: Previous studies have demonstrated that microvolt T-wave alternans
      (MTWA) testing is a robust predictor of ventricular tachyarrhythmias and sudden
      cardiac death (SCD) in at-risk patients. However, recent studies have suggested
      that MTWA testing is not as good a predictor of "appropriate" implantable
      cardioverter-defibrillator (ICD) therapy as it is a predictor of SCD in patients
      without ICDs. OBJECTIVE: To evaluate the utility of MTWA testing for SCD risk
      stratification in patients without ICDs. METHODS: Patient-level data were
      obtained from 5 prospective studies of MTWA testing in patients with no history
      of ventricular arrhythmia or SCD. In these studies, ICDs were implanted in only a
      minority of patients and patients with ICDs were excluded from the analysis. We
      conducted a pooled analysis and examined the 2-year risk for SCD based on the
      MTWA test result. RESULTS: The pooled cohort included 2883 patients. MTWA testing
      was positive in 856 (30%), negative in 1627 (56%), and indeterminate in 400 (14%)
      patients. Among patients with a left ventricular ejection fraction (LVEF) of
      <=35%, annual SCD event rates were 4.0%, 0.9%, and 4.6% among groups with MTWA
      positive, negative, and indeterminate test results. The SCD rate was
      significantly lower among patients with a negative MTWA test result than in
      patients with either positive or indeterminate MTWA test results (P <.001 for
      both comparisons). In patients with an LVEF of >35%, annual SCD event rates were
      3.0%, 0.3%, and 0.3% among the groups with MTWA positive, negative, and
      indeterminate test results. The SCD rate associated with a positive MTWA test
      result was significantly higher than that associated with either negative (P
      <.001) or indeterminate MTWA test results (P = .003). CONCLUSIONS: In patients
      without ICDs, MTWA testing is a powerful predictor of SCD. Among patients with an
      LVEF of <=35%, a negative MTWA test result is associated with a low risk for SCD.
      Conversely, among patients with an LVEF of >35%, a positive MTWA test result
      identifies patients at significantly heightened SCD risk. These findings may have
      important implications for refining primary prevention ICD treatment algorithms.

PMID- 22406386
TI  - Neuropeptide Y: identification of a novel rat mRNA splice-variant that is
      downregulated in the hippocampus and the prefrontal cortex of a depression-like
      model.
AB  - Neuropeptide Y (NPY) is known to influence emotional processing and decreased NPY
      levels have been associated with mood and anxiety disorders. Alternative splicing
      of pre-messenger RNA is a cellular mechanism that allows for transcriptome
      diversity, yet there is limited knowledge in this respect with regard to Npy.
      Since the hippocampus and the prefrontal cortex play an important role in
      affective disorders, we investigated alternative splicing of Npy in these regions
      of a rat model of depression (Flinders Sensitive Line, FSL) and its controls
      (Flinders Resistant Line, FRL). The existence of different Npy messenger RNA
      (mRNA) variants was examined using 5' and 3' RACE. In addition to the Npy mRNA
      species annotated in GenBank and Ensembl, we identified a novel "short" mRNA
      splice variant. Immunoblotting results argued against a putative translation of
      this "short" mRNA into protein in brain tissue. Compared to the FRL, the FSL had
      reduced "short"Npy mRNA levels in the HIP (P=0.00014) and the PFC (P=0.016). Gene
      expression analyses in five brain regions of an outbred rat strain supported the
      presence of the "short"Npy transcript in all examined regions and showed that it
      is expressed in ~2.4-fold lower levels than the "long"Npy mRNA. Finally,
      sequencing of the 5' RACE products revealed a transcription start site of Npy
      that is different from the currently annotated position. These data add to the
      characterization of the rat Npy mRNA and demonstrate the presence of a novel
      transcript with a so far unknown function.

PMID- 22406387
TI  - Adults may be used to alleviate weaning stress in domestic foals (Equus
      caballus).
AB  - The present study aims to investigate whether the presence of unrelated adult
      horses at weaning would reduce the social stress of weaning and the emergence of
      undesirable behaviours. We tested this hypothesis in 32 domestic foals by
      comparing short and medium term behavioural and physiological responses to
      weaning in foals maintained in homogeneous groups of peers (PW) to those of foals
      grouped with both peers and unrelated adults (AW). In total, three trials were
      conducted, which each trial consisting of one AW group and one PW group. In all
      foals, weaning was followed by increased vocalization, increased locomotion and
      increased salivary cortisol concentration. However, signs of stress were less
      pronounced and shorter in duration in weanlings housed with unrelated adults
      (e.g., whinnies: p<0.05; salivary cortisol: p<0.05). Only foals without adults
      exhibited increased aggressiveness towards peers (p<0.05) and abnormal behaviours
      (p<0.05) such as excessive wood-chewing and redirected sucking towards peers. In
      conclusion, introducing adults to minimize weaning stress in foals and later on
      aggressiveness and abnormal behaviours appears as the most promising approach to
      date.

PMID- 22406389
TI  - Disturbed emotion recognition in patients with narcissistic personality disorder.
AB  - Although theoretically the lack of empathy is a supposed key symptom of
      narcissistic personality disorder (NPD), empirical studies examining empathy in
      NPD are scarce. In the present study it was examined whether patients with NPD
      differ from healthy controls and a psychiatric control group in their empathic
      abilities. In order to examine this question, 20 patients with NPD, 20 patients
      with a personality disorder in the Cluster C spectrum and 20 healthy control
      participants were presented with a questionnaire and a facial recognition task
      designed to measure empathic abilities. It was found that patients with NPD did
      not differ from the two control groups on a self-report questionnaire indicating
      that patients regard themselves as sensitive to the feelings of others. On the
      contrary, it was found NPD patients generally performed worse on a facial emotion
      recognition task compared to both control groups. In addition to this general
      deficit in emotion recognition, patients with NPD showed a specific deficit for
      emotions representing fear and disgust. These results provide the first empirical
      evidence for impaired emotion recognition in patients with NPD.

PMID- 22406388
TI  - Oxytocin receptor and Mecp2 308/Y knockout mice exhibit altered expression of
      autism-related social behaviors.
AB  - The development of tasks measuring behaviors specific to the three major symptom
      categories for autism makes it possible to differentiate mouse models of autism
      spectrum disorders (ASD) in terms of changes in these specific categories. Prior
      studies indicate that BTBR T+tf/J mice, the strain that has been evaluated most
      extensively, show autism-relevant changes in all three symptom categories;
      reciprocal social interactions; communication; and repetitive, ritualized
      behaviors. This report reviews the behaviors of oxytocin receptor (Oxtr) and
      Mecp2(308/Y) wild-type (WT) and knockout (KO) mice, in a number of tests
      specifically designed to provide information on behaviors that may show
      functional parallels to the core symptoms of ASD. Oxtr KO mice show robust
      decreases in reciprocal social interactions, and reduced levels of communication,
      but no changes in repetitive, ritualized behaviors; whereas Mecp2(308/Y) KO mice
      show a slight but consistent enhancement of social behavior and communication,
      and no changes in repetitive, ritualized behaviors. This data base, although
      small, strongly indicates that mouse models can sort the diagnostic symptoms of
      autism, and suggests that biological and physiological analyses of these strains
      may be capable of providing differential information on the brain systems
      involved in particular symptoms of this disorder. Profiles of behavioral changes
      in other mouse models of ASD should provide additional specificity in the search
      for biomarkers associated with particular ASD symptoms and symptom clusters.

PMID- 22406390
TI  - The role of persistent and incident major depression on rate of cognitive
      deterioration in newly diagnosed Alzheimer's disease patients.
AB  - Depression may potentially impair the clinical course of Alzheimer's disease
      (AD). Thus, the aim of this study was to investigate cognitive progression of AD
      patients with or without major depressive episode (MDE). In this 1-year
      longitudinal follow-up study conducted in three Italian memory clinics, 119 newly
      diagnosed probable AD patients of mild severity, who were not undergoing
      treatment with an acetyl-cholinesterase inhibitor (AChEI), and had not been
      treated with psychotropic drugs in the last 2 years, were included. Patients were
      assessed to investigate the effect of baseline and 1-year follow-up MDE (using
      modified DSM-IV diagnostic criteria for MDE in AD) on progression of global
      cognitive deterioration (using Mini-Mental State Examination (MMSE)), adjusted
      for confounding factors. Never being depressed was associated with a 3.1 (95%CI
      1.0-10.1) increased risk of MMSE decline compared to recovered depression. Six
      times more patients with persistent depression had MMSE decline compared to
      patients with recovered depression. However, the largest odds (7.3; 95%CI 1.4
      38.1) of cognitive decline was observed in patients who developed incident
      depression over follow-up. In conclusion, persistent or incident depression
      worsens cognitive outcome while no or recovered depression does not affect it in
      early AD patients.

PMID- 22406391
TI  - External ear abnormalities in existing scales for minor physical anomalies: are
      they enough?
AB  - The pattern of external ear abnormalities in patients with schizophrenia and
      bipolar disorder was studied. Sixty-seven male patients having schizophrenia
      (n=30) and bipolar disorder (n=37) were examined using a scale constructed for
      the study. Stepwise logistic regression analysis showed that 'prominent crux of
      helix' and 'ear lobe crease' could differentiate between schizophrenia and
      bipolar disorder. These external ear abnormalities need further characterization
      and consideration for possible inclusion in scales that assess minor physical
      anomalies.

PMID- 22406392
TI  - A taxometric investigation of the latent structure of eating disorders.
AB  - The present study examined the latent structure of eating disorder symptoms in a
      large sample of patients with a diagnosis of anorexia nervosa restricting type,
      anorexia nervosa binge eating/purging type, and bulimia nervosa (n=3747). Three
      taxometric procedures (MAXimum EIGenvalue (MAXEIG), Mean Above Minus Below A
      (MAMBAC), and Latent-Mode Factor Analysis (L-Mode)) were applied to self-reported
      symptoms of bulimia, drive for thinness, body dissatisfaction, as well as body
      mass index. Taxometric analysis among patients with the restricting and binge
      eating/purging subtype of anorexia and those with bulimia nervosa supported a
      dimensional latent structure of eating disorder symptoms. Taxometric analysis
      also revealed a dimensional latent structure of eating disorder symptoms among
      patients with the restricting and binge eating/purging subtype of anorexia
      suggesting that the two anorexia subtypes may not represent discrete categories.
      These findings suggest that the diagnosis and assessment of eating disorder
      symptoms should be conceptualized from a dimensional framework.

PMID- 22406393
TI  - Gut feelings, deliberative thought, and paranoid ideation: a study of
      experiential and rational reasoning.
AB  - Rapid intuitive hunches or gut feelings may be a compelling source of evidence
      for paranoid ideas. Conversely, a failure to apply effortful analytic thinking
      may contribute to the persistence of such thoughts. Our main aim was to examine
      for the first time the associations of persecutory thinking with experiential and
      rational thinking styles. Five hundred individuals recruited from the general
      population completed self-report assessments of current persecutory ideation,
      general reasoning styles and personality traits. Persecutory ideation was
      independently associated with greater use of experiential reasoning and less use
      of rational reasoning. The correlations were small. Persecutory ideation was also
      positively associated with neuroticism and negatively correlated with
      extraversion, agreeableness and conscientiousness. There was no evidence of an
      interaction between neuroticism and experiential reasoning in the prediction of
      paranoia, but high experiential reasoning in the context of low rational
      reasoning was particularly associated with persecutory ideation. Overall, the
      study provides rare evidence of self-reported general reasoning styles being
      associated with delusional ideation. Perceived reliance on intuition is
      associated with paranoid thinking, while perceived reliance on deliberation is
      associated with fewer such thoughts. The dual process theory of reasoning may
      provide a framework to contribute to the understanding of paranoid thinking.

PMID- 22406394
TI  - Direct and indirect forms of non-suicidal self-injury: evidence for a
      distinction.
AB  - Non-suicidal self-injury (NSSI) involves deliberate acts (such as cutting) that
      directly damage the body but occur without suicidal intent. However, other non
      suicidal behaviors that involve people mistreating or abusing themselves but that
      do not deliberately and directly damage bodily tissue may have much in common
      with NSSI. Such 'indirect' methods of self-injury might include involvement in
      abusive relationships, substance abuse, risky or reckless behavior, or eating
      disordered behavior. Using a community sample (N=156) we compared individuals
      engaging in NSSI (n=50), indirect (non-suicidal) self-injurers (n=38), and
      healthy controls (n=68) on a range of clinical and personality characteristics.
      As predicted, non-suicidal self-injurers and indirect self-injurers showed more
      pathology than healthy controls on all measures. Comparisons of the NSSI and the
      Indirect self-injury groups revealed no significant differences on measures of
      dissociation, aggression, impulsivity, self-esteem, negative temperament,
      depressive symptoms, and borderline personality disorder. However, compared to
      people who engaged only in indirect forms of self-injury, those who engaged in
      NSSI were more self-critical, had higher scores on a measure of suicide
      proneness, and had a history of more suicide attempts. The findings suggest that
      NSSI and indirect self-injury are best viewed as separate and distinct clinical
      phenomena.

PMID- 22406395
TI  - Comparison of objectively measured motor behavior with ratings of the motor
      behavior domain of the Bern Psychopathology Scale (BPS) in schizophrenia.
AB  - Motor symptoms in schizophrenia occur frequently and are relevant to diagnosis
      and antipsychotic therapy. To date motor symptoms are difficult to assess and
      their pathobiology is a widely unresolved issue. The Bern Psychopathology Scale
      for the assessment of system-specific psychotic symptoms (BPS) was designed to
      identify homogenous patient groups by focusing on three domains: language,
      affectivity and motor behavior. The present study aimed to validate the motor
      behavior domain of the BPS using wrist actigraphy. In total, 106 patients were
      rated with the BPS and underwent 24 h continuous actigraphy recording. The
      ratings of the global severity of the motor behavior domain (GSM) as well as the
      quantitative and the subjective items of the motor behavior domain of the BPS
      were significantly associated with actigraphic variables. In contrast, the
      qualitative items of the motor domain failed to show an association with
      actigraphy. Likewise, scores of the language and the affectivity domains were not
      related to actigraphic measures. In conclusion, we provided substantial external
      validity for global, quantitative and subjective ratings of the BPS motor
      behavior domain. Thus, the BPS is suitable to assess the dimension of
      quantitative motor behavior in the schizophrenia spectrum.

PMID- 22406396
TI  - Self-awareness of cognitive functioning in schizophrenia: patients and their
      relatives.
AB  - Cognitive impairment has been recognized since the earliest descriptions of
      schizophrenia as a core feature of the illness and different programmes have been
      developed to remediate these deficits. In all likelihood it is important for
      compliance and adherence to treatment that not only the patients but also their
      relatives be aware of the patients; cognitive deficits. Sixty-two patients with a
      diagnosis of schizophrenia and, for each one of them, one family member and an
      informant from the medical staff, were recruited and administered the
      Schizophrenia Cognition Rating Scale (SCoRS) ratings. Patients were tested for
      cognitive deficits with a neuropsychological battery and their performance was
      compared to the ratings of cognitive functioning provided by the patient himself,
      his family member and the informant. Results show no significant association
      between cognitive performance and SCoRS ratings in patients; only for executive
      functions the patient's performance was found to be predictive of the respective
      judgment on the SCoRS that was given by the relative. This is the first study to
      investigate awareness of the patients' cognitive deficits, both in the patients
      themselves and in their first degree relatives, through a direct comparison
      between subjective clinical ratings and objective measures of cognitive
      performances. When both patients and relatives are unaware of the patients'
      cognitive deficits, this could affect adherence to remediation treatment and need
      to be specifically addressed in future rehabilitation strategies.

PMID- 22406397
TI  - Daily distribution of atrial arrhythmic episodes in sick sinus syndrome patients:
      implications for atrial arrhythmia monitoring.
AB  - AIMS: Disorders such as paroxysmal atrial fibrillation (AF) and atrial
      tachyarrhythmias (AT) are difficult to investigate because of their intermittent,
      and sometimes asymptomatic, nature. The aim of this study was to investigate the
      daily temporal distribution of AT/AF episodes--onset and occurrence--by analysing
      data from 250 pacemaker-implanted, brady-tachy syndrome patients who have been
      enrolled in the Burden II Study. METHODS AND RESULTS: Data were analysed
      accounting for the mode switch list which includes date, time, and duration of
      each mode switch episode. Chi-squared tests for goodness of fit were used to
      determine whether AT/AF episode were uniformly distributed. The population
      analysed in the present study suggests the occurrence of a circadian rhythm of
      paroxysmal AF episodes, similar to that described for other cardiovascular
      diseases, with clustering of events in the morning from 08:00 and (to a lesser
      degree) in the afternoon (03:00 to 18:00). The relative risk of AT/AF onset is
      13% higher during daytime, 40% lower at night (P < 0.000001). CONCLUSION: The use
      of monitoring devices based on daily electrocardiogram (ECG) recording could be
      optimized with these data, thus increasing the probability to detect AT/AF
      episodes.

PMID- 22406398
TI  - 1H NMR-based metabonomics study of the urinary biochemical changes in Kansui
      treated rat.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The dried root of Kansui (Euphorbia kansui L.) is
      a commonly used and effective traditional Chinese medicine (TCM). AIM OF THE
      STUDY: We combined the urinary metabolites alteration and traditional assays of
      Kansui-induced rats to discuss the mechanism of toxicity of Kansui. MATERIALS AND
      METHODS: The Sprague-Dawley rats were dosed with 7.875g Kansui/kg weight and
      15.75g Kansui/kg weight. Urine samples were collected at day -1 (before
      treatment), and days 7, 14 and 21 for NMR analysis. Plasma and liver and kidney
      tissues were collected at day 14 for biochemical assays and histopathological
      examination, respectively. RESULTS: The metabonome of rats treated with Kansui
      differed markedly from that of the controls. This was confirmed by the
      histopathology of liver and kidney tissue and clinical biochemistry analysis. The
      toxicity of Kansui accumulated with dosing time, and persisted even when
      treatment was stopped. The corresponding biochemical pathways alterations
      included inhibited TCA cycle, increased anaerobic glycolysis, and perturbed amino
      acids metabolism. CONCLUSION: The biochemical pathways disorder conjunction with
      histopathology changes provides new clues to evaluate the toxicity of Kansui from
      a systematic and holistic view.

PMID- 22406399
TI  - The obesity paradox: time for a new look at an old paradigm.

PMID- 22406402
TI  - Analysis using fish of sperm and embryos from two carriers of rare rob(13;21) and
      rob(15;22) robertsonian translocation undergoing PGD.
AB  - The majority of fluorescence in situ hybridization (FISH) studies on the meiotic
      segregation of Robertsonian translocations focus on the most common types,
      rob(13; 14) and rob(14; 21). Here we report the first study for carriers of rare
      Robertsonian translocations rob(13; 21) and rob(15; 22) combining analysis of
      meiotic segregation in sperm and blastomeres following pre-implantation genetic
      diagnosis (PGD). Dual-colour FISH was applied to nuclei from spermatozoa and
      blastomeres from PGD embryos using two subterminal contig probes for each
      translocation, and a second round with probes for chromosomes 16 and 18. Patient
      1 had a rob(13; 21) and patient 2 had a rob(15; 22), and 86.3% and 87.5% of
      gametes respectively were consistent with meiotic segregation resulting in a
      normal or balanced chromosome complement. Analysis of embryos showed that for
      patient 1 and 2 respectively, 25% and 46% were balanced, and of the unbalanced
      embryos, 50% and 31% were mosaic or chaotic. Our patients with a rob(13; 21) and
      rob(15; 22) were found to have a similar meiotic segregation pattern to that for
      male carriers of the common Robertsonian translocations. The observed rate in
      unbalanced embryos being mosaic or chaotic may result in an increased risk of
      chromosomal abnormalities. Our results may help to improve the genetic counseling
      for carriers of rare Robertsonian translocations.

PMID- 22406401
TI  - Interstitial deletion of chromosome 2p15-16.1: report of two patients and
      critical review of current genotype-phenotype correlation.
AB  - We report two individuals with developmental delay and dysmorphic features, in
      whom array-based comparative genomic hybridization (array CGH) led to the
      identification of a 2p15p16.1 de novo deletion. In the first patient (Patient 1)
      a familial deletion of 6q12, inherited from her father, was also detected. In the
      second patient (Patient 2) in addition to the 2p15p16.1 microdeletion a de novo
      deletion in Xq28 was detected. Both individuals shared dysmorphic features and
      developmental delay with the six reported patients with a 2p15p16.1 microdeletion
      described in medical literature. CONCLUSION: in the first patient a 642 kb 2p16.1
      deletion (from 60.604 to 61.246 Mb), and a 930 kb 6q12 familial deletion, was
      detected and in the second a 2.5 Mb 2p15p16.1 deletion (from 60.258 to 62.763
      Mb), with a Xq28 deletion, was discovered. The common dysmorphic features and
      neurodevelopmental delay found in these patients are in agreement with the
      clinical phenotype of a microdeletion syndrome involving 2p15p16.1. Our data
      confirm the hypothesis suggesting that 2p15p16.1 deletion is a contiguous gene
      syndrome.

PMID- 22406400
TI  - MicroRNA dysregulation in neuropsychiatric disorders and cognitive dysfunction.
AB  - MicroRNAs (miRNA), a class of non-coding RNAs, are emerging as important
      modulators of neuronal development, structure and function. A connection has been
      established between abnormalities in miRNA expression and miRNA-mediated gene
      regulation and psychiatric and neurodevelopmental disorders as well as cognitive
      dysfunction. Establishment of this connection has been driven by progress in
      elucidating the genetic etiology of these phenotypes and has provided a context
      to interpret additional supporting evidence accumulating from parallel expression
      profiling studies in brains and peripheral blood of patients. Here we review
      relevant evidence that supports this connection and explore possible mechanisms
      that underlie the contribution of individual miRNAs and miRNA-related pathways to
      the pathogenesis and pathophysiology of these complex clinical phenotypes. The
      existing evidence provides useful hypotheses for further investigation as well as
      important clues for identifying novel therapeutic targets.

PMID- 22406403
TI  - Does clinical incident seriousness and receipt of work-based support influence
      mood experienced by nurses at work? A behavioural diary study.
AB  - BACKGROUND: While the relationship between general perceptions of the work
      environment and negative mood is well detailed, little is known about the effect
      of specific clinical incident characteristics on the mood experienced at work by
      nurses. This study examines the effect of incident seriousness and receipt of
      work-based support in the worst event of a shift from managers and colleagues on
      the Negative and Positive Affect experienced by nurses at work. METHODS: We
      approached the total cohort of medical and surgical nurses in 4 large district
      general hospitals in England, 17% volunteered. Some 171 nurses filled end of
      shift and standard entry (every 90 min) computerised behavioural diaries over
      three consecutive shifts. The diaries measured Incident Seriousness, Receipt of
      Managerial and Co-worker Support, Negative Affect and Positive Affect. Results
      were analysed using multilevel modelling (MLwiN 2.19). FINDINGS: Following the
      worst clinical incident of a shift, nurses reported higher Negative Affect
      (beta=1.28, [95%CI: 0.12, 2.45], z=2.17, p<.05) and lower Positive Affect (beta=
      2.39, [95%CI: -3.96, -0.82], z=2.99, p<.005) which persisted for the remainder of
      the shift. Most critically, Negative Affect was more elevated after serious
      incidents (beta=0.07, [95%CI: 0.04, 0.10], z=3.5, p<.005). Nurses who reported
      Receipt of Managerial Support following an incident reported significantly lower
      levels of Positive Affect compared to those reporting no such contact (beta=
      5.30, [95%CI: -9.51, -1.09], z=2.47, p<.05). The interaction between Incident and
      the Receipt of Work-Based Support on NA was not significant (beta=2.34 [95%CI: 
      0.82, 3.95], z=1.45, p>.05). Receipt of Colleague Support had no relationship
      with Negative Affect or Positive Affect. Free text reports mainly revealed the
      negative impact of managerial support, although there were instances of contact
      with managers which were sought following exposure to difficult clinical
      situations. DISCUSSION: Serious clinical incidents have enduring effects on
      Negative Affect and Positive Affect for the remainder of the shift. Nurse
      Positive Affect was significantly worse following the worst clinical incident of
      shift when managerial support was received. Further research is required to
      determine the positive and negative effects of managerial support on the mood
      experienced by nurses at work.

PMID- 22406405
TI  - Translational regulation by the 5'-UTR of thyroid hormone receptor alpha mRNA.
AB  - Thyroid hormone (TH) regulates gene transcription by binding to the thyroid
      hormone receptor (TR) and plays a critical role in the regulation of development,
      growth and metabolism. The ligated TR activates many effector genes, which
      contributes to the orchestrated remodelling of the amphibian metamorphosis.
      However, the mechanisms regulating TRalpha protein level remain unknown. We
      determined the nucleotide sequences of the 5'-untranslated regions (5'-UTRs) in
      amphibian TRalpha mRNAs. The TRalpha 5'-UTR contains evolutionarily conserved
      regions. We demonstrated that a 161-nt stretch of the Xenopus TRalpha 5'-UTR
      strongly represses the translation of the downstream open reading frame in both
      frog and human cell lines, as well as in a cell-free translation system. An
      analysis using successive deletions of the TRalpha 5'-UTR revealed five elements
      possessing translational repressive activity. We analysed two elements, the 14-nt
      GC-rich region and the 15-nt upstream open reading frame (uORF), by introducing
      point mutations. This analysis showed that the GC-rich region, which shares its
      nucleotide sequence with the Sp1-binding site, requires stringent sequence
      specificity at a nucleotide level for translational repression to take place,
      whereas under our study conditions, the uORF does not. This study provides an
      example of complex translational regulation by multiple elements.

PMID- 22406404
TI  - Hormonal therapy in breast cancer: a model disease for the personalization of
      cancer care.
AB  - The treatment of breast cancer is driven by subtype classification, of which the
      assessment of hormone receptor status is one of the important determinants of
      therapy. The use of hormonal therapy to treat estrogen-receptor positive breast
      cancer has been studied for over a century and is one of the well-described uses
      of personalized medicine. In this review, we will describe the classification of
      hormone receptor status and the various endocrine treatment strategies.
      Opportunities for personalization of care are illustrated.

PMID- 22406406
TI  - Membrane-displayed peptide ligand activates the pheromone response pathway in
      Saccharomyces cerevisiae.
AB  - The budding yeast, Saccharomyces cerevisiae, is an attractive host for studying G
      protein-coupled receptors (GPCRs). We developed a system in which a peptide
      ligand specific for GPCR is displayed on yeast plasma membrane. The model system
      described here is based on yeast plasma membrane display of an analogue of alpha
      factor, which is a peptide ligand for Ste2p, the GPCR that activates the yeast
      pheromone response pathway. alpha-Factor analogues, containing linkers of varying
      lengths and produced in yeast cells, became attached to the cell plasma membrane
      by linking to the glycosylphosphatidylinositol (GPI)-anchored plasma membrane
      protein Yps1p. We were able to demonstrate that an optimized alpha-factor
      analogue activated the pheromone response pathway in S. cerevisiae, as assessed
      by a fluorescent reporter assay. Furthermore, it was shown that linker length
      strongly influenced signalling pathway activation. To our knowledge, this is the
      first report documenting functional signalling by a plasma membrane-displayed
      ligand in S. cerevisiae.

PMID- 22406407
TI  - Early membrane initiated transcriptional effects of estrogens in breast cancer
      cells: First pharmacological evidence for a novel membrane estrogen receptor
      element (ERx).
AB  - The complexity of estrogen actions mainly relies to the presence of different
      identified receptors (ERalpha, ERbeta, their isoforms, and GPR30/GPER) and their
      discrete cellular distribution. Depending on the localization of the receptor
      that mediates estrogen effects, nuclear and extra-nuclear actions have been
      described. The latter can trigger a number of signaling events leading also to
      transcriptional modifications. In an attempt to clarify the nature of the
      receptor(s) involved in the membrane initiated effect of estrogens on gene
      expression, we performed a whole transcriptome analysis of breast cancer cell
      lines with different receptor profiles (T47D, MCF7, MDA-MB-231, SK-BR-3). A
      pharmacological approach was conducted with the use of estradiol (E(2)) or
      membrane-impermeable E(2)-BSA in the absence or presence of a specific ERalpha
      beta or GPR30/GPER antagonist. Our results clearly show that in addition to the
      ERalpha isoforms and/or GPR30/GPER that mainly mediate the transcriptional effect
      of E(2)-BSA, there is a specific transcriptional signature (found in T47D and MCF
      7 cells) suggesting the presence of an unidentified membrane ER element (ERx).
      Analysis of its signature and phenotypic verification revealed that important
      cell function such as apoptosis, transcriptional regulation, and growth factor
      signaling are associated with ERx.

PMID- 22406408
TI  - The cultivation of human retinal pigment epithelial cells on Bombyx mori silk
      fibroin.
AB  - We have presently evaluated membranes prepared from Bombyx mori silk fibroin
      (BMSF), for their potential use as a prosthetic Bruch's membrane and carrier
      substrate for human retinal pigment epithelial (RPE) cell transplantation. Porous
      BMSF membranes measuring 3 MUm in thickness were prepared from aqueous solutions
      (3% w/v) containing poly(ethylene oxide) (0.09%). The permeability coefficient
      for membranes was between 3 and 9 * 10(-5) cm/s by using Allura red or 70 kDa
      FITC-dextran respectively. Average pore size (+/-sd) was 4.9 +/- 2.3 MUm and 2.9
      +/- 1.5 MUm for upper and lower membrane surfaces respectively. Optimal
      attachment of ARPE-19 cells to BMSF membrane was achieved by pre-coating with
      vitronectin (1 MUg/mL). ARPE-19 cultures maintained in low serum on BMSF
      membranes for approximately 8 weeks, developed a cobble-stoned morphology
      accompanied by a cortical distribution of F-actin and ZO-1. Similar results were
      obtained using primary cultures of human RPE cells, but cultures took noticeably
      longer to establish on BMSF compared with tissue culture plastic. These findings
      encourage further studies of BMSF as a substrate for RPE cell transplantation.

PMID- 22406409
TI  - Species-level phylogeny of 'Satan's perches' based on discordant gene trees
      (Teleostei: Cichlidae: Satanoperca Gunther 1862).
AB  - Neotropical rivers are home to the largest assemblage of freshwater fishes, but
      little is known about the phylogeny of these fishes at the species level using
      multi-locus molecular markers. Here, we present a phylogeny for all known species
      of the genus Satanoperca, a widespread group of Neotropical cichlid fishes, based
      on analysis of six unlinked genetic loci. To test nominal and proposed species
      limits for this group, we surveyed mtDNA sequence variation among 320 individuals
      representing all know species. Most nominal species were supported by this
      approach but we determined that populations in the Xingu, Tapajos, and
      Araguaia+Parana Rivers are likely undescribed species, while S. jurupari and S.
      mapiritensis did not show clear genetic distinction. To infer a phylogeny of
      these putative species, we conducted maximum likelihood and Bayesian non-clock
      and relaxed clock analyses of concatenated data from three genes (one
      mitochondrial, two nuclear). We also used a multi-species coalescent model to
      estimate a species tree from six unlinked loci (one mitochondrial, five nuclear).
      The topologies obtained were congruent with other results, but showed only
      minimal to moderate support for some nodes, suggesting that more loci will be
      needed to satisfactorily estimate the distribution of coalescent histories within
      Satanoperca. We determined that this variation results from topological
      discordance among separate gene trees, likely due to differential sorting of
      ancestral polymorphisms.

PMID- 22406410
TI  - Re: Molecular characterisation of Staphylococcus aureus carrying the Panton
      Valentine leukocidin gene in northern Spain.

PMID- 22406411
TI  - Hospitalizations from pandemic influenza (pH1N1) infections among patients with
      asthma or COPD in Spain.

PMID- 22406412
TI  - Molecular epidemiology and nasal carriage of Staphylococcus aureus and
      methicillin-resistant S. aureus among young children attending day care centers
      and kindergartens in Hong Kong.
AB  - OBJECTIVES: To investigate the prevalence and molecular epidemiology of
      Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) nasal carriage
      in children. METHODS: We collected nasal and nasopharyngeal swabs from 2211
      children aged 2-5 years attending 79 day care centers (DCCs) and 113
      kindergartens (KGs) in all 18 geographical districts in Hong Kong. RESULTS: The
      overall carriage rates of S. aureus and MRSA were 27.6% (95% confidence interval
      [CI], 24.8-28.5%) and 1.3% (95% CI, 0.8-1.8%), respectively. Molecular typing
      (staphylococcal cassette chromosome mec [SCCmec], sequence type [ST], clonal
      cluster [CC]) showed that all the 28 MRSA isolates had SCCmec IV (n = 13) or V (n
      = 15) including 12 isolates with community-associated-MRSA genotypes (ST59-IV/V,
      ST30-IV and ST88-V), 10 isolates with healthcare-associated-MRSA genotypes (ST45
      IV/V, CC5-IV and ST630-V) and six isolates with novel genotypes (ST10-V and CC1
      IV). Spa typing indicated that there was some within and between DCCs/KGs
      transmission of certain MRSA and methicillin-sensitive S. aureus strains but this
      was not extensive. CONCLUSION: Our findings indicate the potential for DCCs to be
      a reservoir for emerging MRSA genotypes and highlight the need to enhance
      education and infection control measures to reduce their cross-transmission in
      this population.

PMID- 22406415
TI  - Neuroprotective effects of extremely low-frequency electromagnetic fields on a
      Huntington's disease rat model: effects on neurotrophic factors and neuronal
      density.
AB  - There is evidence to suggest that the neuroprotective effect of exposure of
      extremely low-frequency electromagnetic fields (ELF-EMF) may be due, at least in
      part, to the effect of these fields on neurotrophic factors levels and cell
      survival, leading to an improvement in behavior. This study was undertaken to
      investigate the neuroprotective effects of ELFEF in a rat model of 3
      nitropropionic acid (3NP)-induced Huntington's disease. Behavior patterns were
      evaluated, and changes in neurotrophic factor, cell damage, and oxidative stress
      biomarker levels were monitored in Wistar rats. Rats were given 3NP over four
      consecutive days (20 mg/kg body weight), whereas ELFEF (60 Hz and 0.7 mT) was
      applied over 21 days, starting after the last injection of 3NP. Rats treated with
      3NP exhibited significantly different behavior in the open field test (OFT) and
      the forced swim test (FST), and displayed significant differences in neurotrophic
      factor levels and oxidative stress biomarkers levels, together with a neuronal
      damage and diminished neuronal density, with respect neuronal controls. ELFEF
      improved neurological scores, enhanced neurotrophic factor levels, and reduced
      both oxidative damage and neuronal loss in 3NP-treated rats. ELFEF alleviates 3NP
      induced brain injury and prevents loss of neurons in rat striatum, thus showing
      considerable potential as a therapeutic tool.

PMID- 22406413
TI  - Strategies to defeat ketamine-induced neonatal brain injury.
AB  - Studies using animal models have shown that general anesthetics such as ketamine
      trigger widespread and robust apoptosis in the infant rodent brain. Recent
      clinical evidence suggests that the use of general anesthetics on young children
      (at ages equivalent to those used in rodent studies) can promote learning
      deficits as they mature. Thus, there is a growing need to develop strategies to
      prevent this injury. In this study, we describe a number of independent
      approaches to address therapeutic intervention. Postnatal day 7 (P7) rats were
      injected with vehicle (sterile PBS) or the NMDAR antagonist ketamine (20 mg/kg).
      After 8 h, we prepared brains for immunohistochemical detection of the pro
      apoptotic enzyme activated caspase-3 (AC3). Focusing on the somatosensory cortex,
      AC3-positive cells were then counted in a non-biased stereological manner. We
      found AC3 levels were markedly increased in ketamine-treated animals. In one
      study, microarray analysis of the somatosensory cortex from ketamine-treated P7
      pups revealed that expression of activity dependent neuroprotective protein
      (ADNP) was enhanced. Thus, we injected P7 animals with the ADNP peptide fragment
      NAPVSIPQ (NAP) 15 min before ketamine administration and found we could dose
      dependently reverse the injury. In separate studies, pretreatment of P6 animals
      with 20 mg/kg vitamin D(3) or a nontoxic dose of ketamine (5 mg/kg) also
      prevented ketamine-induced apoptosis at P7. In contrast, pretreatment of P7
      animals with aspirin (30 mg/kg) 15 min before ketamine administration actually
      increased AC3 counts in some regions. These data show that a number of unique
      approaches can be taken to address anesthesia-induced neurotoxicity in the infant
      brain, thus providing MDs with a variety of alternative strategies that enhance
      therapeutic flexibility.

PMID- 22406414
TI  - Relation between changes in neural responsivity and reductions in desire to eat
      high-calorie foods following gastric bypass surgery.
AB  - Reductions in reward-related (e.g. striatal) neural activation have been noted
      following obesity surgery. It has been speculated that these postoperative neural
      changes may be related to documented postoperative changes in food preferences;
      however, this relation has not been previously established. In this study,
      functional magnetic resonance imaging and rating scales were used to assess
      neural responsivity, desire to eat (i.e. wanting), and liking for high- and low
      calorie food cues in 14 females one month pre- and one month post-Roux-en-Y
      gastric bypass (RYGB) surgery. Pre- to post-RYGB changes in all variables were
      assessed, and postoperative changes in neural responsivity were regressed on
      postoperative changes in desire to eat and liking of foods. Results revealed
      significant postoperative reductions in mesolimbic (e.g. striatal) neural
      responsivity, desire to eat (wanting), and liking for high- relative to low
      calorie food cues. Postoperative reductions in mesolimbic responsivity were
      associated with postoperative reductions in wanting, but not liking, for high-
      versus low-calorie foods. Interestingly, reductions in food wanting were also
      related to reductions in inhibitory (e.g. dorsolateral prefrontal cortex)
      activation following RYGB. Results are consistent with the hypothesized
      delineation between wanting and liking, supporting the notion that wanting, but
      not liking, is processed through the dopaminergic reward pathway. Concurrent
      reductions in both reward-related and inhibitory activation-predicted reductions
      in desire to eat might suggest that less dietary inhibition was elicited to
      resist potential overconsumption as the anticipated reward value of high-calorie
      foods decreased following RYGB.

PMID- 22406416
TI  - Transduction of E13 murine neural precursor cells by non-immunogenic recombinant
      adeno-associated viruses induces major changes in neuronal phenotype.
AB  - Neural precursor cells (NPCs) provide a cellular model to compare transduction
      efficiency and toxicity for a series of recombinant adeno-associated viruses
      (rAAVs). Results led to the choice of rAAV9 as a preferred candidate to transduce
      NPCs for in vivo transplantation. Importantly, transduction promoted a neuronal
      phenotype characterized by neurofilament M (NFM) with a concomitant decrease in
      the embryonic marker, nestin, without significant change in glial fibrillary
      acidic protein (GFAP). In marked contrast to recent studies for induced
      pluripotent stem cells (iPSCs), exposure to rAAVs is non-immunogenic and these do
      not result in genetic abnormalities, thus bolstering the earlier use of NPCs such
      as those isolated from E13 murine cells for clinical applications. Mechanisms of
      cellular interactions were explored by treatment with genistein, a pan-specific
      inhibitor of protein receptor tyrosine kinases (PRTKs) that blocked the
      transduction and differentiation, thus implying a central role for this pathway
      for inducing infectivity along with observed phenotypic changes and as a method
      for drug design. Implantation of transduced NPCs into adult mouse hippocampus
      survived up to 28 days producing a time line for targeting or migration to
      dentate gyrus and CA3-1 compatible with future clinical applications.
      Furthermore, a majority showed commitment to highly differentiated neuronal
      phenotypes. Lack of toxicity and immune response of rAAVs plus ability for
      expansion of NPCs in vitro auger well for their isolation and suggest potential
      therapeutic applications in repair or replacement of diseased neurons in
      neurodegeneration.

PMID- 22406417
TI  - The inhibitory action of the antimigraine nonsteroidal anti-inflammatory drug
      naproxen on P2X3 receptor-mediated responses in rat trigeminal neurons.
AB  - Enhanced nociceptive firing in trigeminal ganglion neurons is a likely reason for
      migraine pain. In experimental migraine-like conditions induced by the calcitonin
      gene-related peptide (CGRP), P2X3 receptors abundantly expressed in trigeminal
      neurons are highly responsive to the excitatory action of extracellular ATP. In
      this study, we tested whether naproxen, a common antimigraine medicine, could
      affect the function of P2X3 receptors in the presence or absence of the algogen
      nerve growth factor (NGF), the level of which is elevated in patients with
      chronic migraine. We used calcium imaging and patch clamp recordings from rat
      trigeminal neurons, which were activated by a relative specific P2X3 agonist
      alpha,beta-meATP or by high potassium-induced depolarization. In the absence of
      NGF, naproxen dose-dependently (0.1-1 mM) reduced intracellular calcium
      transients elicited by alpha,beta-meATP. Naproxen also led to a slight, but
      significant, reduction in calcium transients induced by potassium ions,
      indicating the involvement of voltage-gated calcium channels. The inhibitory
      action of 1 mM naproxen was enhanced after NGF pretreatment, suggesting that P2X3
      receptors in sensitized neurons are more susceptible to inhibition by high doses
      of this nonsteroidal anti-inflammatory drug (NSAID). Using patch clamp recordings
      from HEK293 cells expressing P2X3 receptors, we tested the direct action of
      naproxen on P2X3 receptor-mediated membrane currents. In clinically relevant
      concentrations of 0.5 mM, naproxen produced a use-dependent blocking effect on
      ATP receptors. Kinetic analysis suggests that naproxen inhibited P2X3 receptors
      via facilitation of fast desensitization, which determines current decay in the
      continuous presence of the agonist. In summary, we present a novel fast mechanism
      for the antimigraine action of naproxen, which can act in synergy with the
      cyclooxygenase inhibition to attenuate headaches.

PMID- 22406418
TI  - Estrogen receptor alpha and beta differentially mediate C5aR agonist evoked Ca2+
      influx in neurons through L-type voltage-gated Ca2+ channels.
AB  - Complement C5a is associated primarily with inflammation. The widespread
      expression of its receptors, C5aR and C5L2 in neuronal cells, however, suggests
      additional regulatory roles for C5a in the CNS. C5aR agonist (PL37-MAP) evokes
      Ca(2+)-influx in GT1-7 neuronal cell line and the Ca(2+)-influx is regulated by
      estradiol. In the present study, we examined further the mechanism of Ca(2+)
      influx and the contribution of the two estrogen receptor (ER) isotypes, ERalpha
      and ERbeta, to estrogenic modulation of intracellular Ca(2+)-content. GT1-7
      neurons were treated with isotype selective ER agonists for 24h then C5aR agonist
      evoked Ca(2+)-responses were measured by Ca(2+)-imaging. Transcriptional changes
      were followed by real-time PCR. We found that not only estradiol (100 pM), but
      the ERalpha selective agonist PPT (100 pM) enhanced the PL37-MAP-evoked Ca(2+)
      influx (E2: 215%, PPT: 175%, compared to the PL37-MAP-evoked Ca(2+)-influx). In
      contrast, the ERbeta selective agonist DPN (100 pM) significantly reduced the
      Ca(2+)-influx (32%). Attenuated Ca(2+)-response (25%) was observed in Ca-free
      environment and depletion of the Ca(2+)-pool by CPA eliminated the remaining
      elevation in the Ca(2+)-content, demonstrating that the majority of Ca(2+)
      originated from the extracellular compartment. L-type voltage-gated Ca(2+)
      channel (L-VGCC) blocker nifedipine abolished the Ca(2+)-influx, while R-type
      Ca(2+)-channel blocker SNX-482 had no effect, exemplifying the predominant role
      of L-VGCC in this process. Acute pre-treatments (8 min) with ER agonists did not
      affect the evoked Ca(2+)-influx, revealing that the observed effects of estrogens
      were genomic. Therefore, we checked estrogenic regulation of C5a receptors and L
      VGCC subunits. ER agonists increased C5aR mRNA expression, whereas they
      differentially regulated C5L2. Estradiol decreased transcription of Ca(v)1.3 L
      VGCC subunit. Based on these results we propose that estradiol may differentially
      modulate C5a-induced Ca(2+)-influx via L-VGCCs in neurons depending on the
      expression of the two ER isotypes.

PMID- 22406419
TI  - LXR and TSPO as new therapeutic targets to increase the levels of neuroactive
      steroids in the central nervous system of diabetic animals.
AB  - Neuroactive steroid levels are decreased in the central nervous system (CNS) of
      streptozotocin (STZ) diabetic rats. In agreement, they exert protective effects
      in this experimental model, counteracting degenerative events occurring in the
      CNS. Therefore, an interesting therapeutic strategy could be to increase their
      levels directly in the CNS. In this study we have evaluated whether activation of
      translocator protein-18kDa (TSPO) or liver X receptors (LXRs) may affect the
      levels of neuroactive steroids present in the CNS of diabetic and non-diabetic
      animals. We observed that the treatment with either Ro5-4864 (i.e., a ligand of
      TSPO) or with GW3965 (i.e., a ligand of LXRs) induced an increase of neuroactive
      steroids in the spinal cord, the cerebellum and the cerebral cortex of STZ-rats,
      but not in the CNS of non-pathological animals. Interestingly, the pattern of
      induction was different among the three CNS areas analyzed and between the two
      pharmacological tools. In particular, the activation of LXRs might represent a
      promising neuroprotective strategy, because the treatment with GW3965, at
      variance to Ro5-4864 treatment, did not induce significant changes in the plasma
      levels of neuroactive steroids. This suggests that activation of LXRs may
      selectively increase the CNS levels of neuroactive steroids avoiding possible
      endocrine side effects exerted by the systemic treatment with these molecules.
      Interestingly GW3965 treatment induced an increase of dihydroprogesterone in the
      spinal cord of diabetic animals in association with an increase of myelin basic
      protein expression. Thus we demonstrated that LXR activation was able to rescue
      CNS symptoms of diabetes.

PMID- 22406420
TI  - Repeat estradiol exposure differentially regulates protein expression patterns
      for estrogen receptor and E-cadherin in older mouse ovarian surface epithelium:
      implications for replacement and adjuvant hormone therapies?
AB  - BACKGROUND: Estrogen replacement therapy increases risk for ovarian epithelial
      cancer, a cancer of mainly older women, yet the response of older ovarian surface
      epithelium (OSE) to repeat estrogen exposure overtime has not been studied. We
      have previously reported significant reductions in estrogen receptor (ER) protein
      expression, particularly the ERbeta1 isoform, in older mouse OSE following a
      single depot estradiol injection. The current study examined OSE from older mice
      following a single, and repeat estradiol injection, given 14 days apart over 28
      days. METHODS: Cohorts of mice were sacrificed 48 hours following each estradiol
      injection, and at three other equidistant time points. Serum and ovarian tissue
      estradiol concentration was correlated to immunohistochemical and morphometric
      parameters used to identify evidence of OSE hyperplasia and hypertrophy. Using
      immunohistochemistry, E-cadherin expression was investigated in OSE 48 hours
      following both estradiol injections, while ERalpha and ERbeta1 expression was
      examined in OSE following repeat estradiol exposure only. RESULTS: First exposure
      to exogenous estradiol resulted in OSE hypertrophy and hyperplasia, and high
      levels of E-cadherin expression. In contrast, repeat estradiol exposure resulted
      in no OSE hyperplasia or hypertrophy, low levels of E-cadherin expression, high
      ERalpha and reduced ERbeta1 protein expression in OSE, and low stromal ERalpha
      expression. Blood and ovarian tissue estradiol levels following repeat estradiol
      injection were half those recorded after a first dose equivalent injection, but
      remained significantly elevated above controls. CONCLUSION: Repeat estradiol
      exposure leads to accumulation of estradiol in ovarian tissue, differentially
      regulating protein expression patterns for E-cadherin in OSE and ER in OSE and
      stroma.

PMID- 22406421
TI  - Desmettianosides A and B, bisdesmosidic furostanol saponins with molluscicidal
      activity from Yucca desmettiana.
AB  - Bioactivity-guided separation of the aqueous methanolic extract of Yucca
      desmettiana leaves, which in a preliminary screening exhibited significant
      molluscicidal activity, led to the isolation and structure elucidation of two new
      steroidal saponins (1 and 2). The structures of desmettianosides A and B,
      identified as bisdesmosidic furostanol glycosides with six and five sugar units,
      respectively, were established by detailed spectroscopic analyses of their NMR
      and MS data. Compounds 1 and 2 exhibited high molluscicidal activity against
      Biomphalaria alexandrina snails with LC100 values of 6 and 11 mg/L, respectively.

PMID- 22406422
TI  - Multiple modes of chromatin remodeling by Forkhead box proteins.
AB  - Forkhead box (FOX) proteins represent a large family of transcriptional
      regulators unified by their DNA binding domain (DBD) known as a 'forkhead' or
      'winged helix' domain. Over 40 FOX genes have been identified in the mammalian
      genome. FOX proteins share significant sequence similarities in the DBD which
      allow them to bind to a consensus DNA response element. However, their modes of
      action are quite diverse as they regulate gene expression by acting as pioneer
      factors, transcription factors, or both. This review focuses on the mechanisms of
      chromatin remodeling with an emphasis on three sub-classes-FOXA, FOXO, and FOXP
      members. FOXA proteins serve as pioneer factors to open up local chromatin
      structure and thereby increase accessibility of chromatin to factors regulating
      transcription. FOXP proteins, in contrast, function as classic transcription
      factors to recruit a variety of chromatin modifying enzymes to regulate gene
      expression. FOXO proteins represent a hybrid subclass having dual roles as
      pioneering factors and transcription factors. A subset of FOX proteins interacts
      with condensed mitotic chromatin and may function as 'bookmarking' agents to
      maintain transcriptional competence at specific genomic sites. The overall
      diversity in chromatin remodeling function by FOX proteins is related to unique
      structural motifs present within the DBD flanking regions that govern selective
      interactions with core histones and/or chromatin coregulatory proteins. This
      article is part of a Special Issue entitled: Chromatin in time and space.

PMID- 22406423
TI  - Comparative cryopreservation of avian spermatozoa: effects of freezing and
      thawing rates on turkey and sandhill crane sperm cryosurvival.
AB  - A comparative approach was used to evaluate semen cooling rates, thawing rates
      and freezing volume on the cryosurvival of avian sperm. Turkey (Meleagris
      gallopavo) and sandhill crane (Grus canadensis) sperm were cryopreserved with
      dimethylacetamide (DMA) concentrations ranging from 6% to 26%. Experiments
      evaluated the efficacy of (1) rapid, moderate and slow cooling rates, (2) rapid
      and slow thawing rates, and (3) final volume of semen frozen (0.2 mL compared to
      0.5 mL). For crane sperm only, additional experiments were conducted to evaluate
      the effect of sucrose on cryosurvival. The functionality of frozen/thawed crane
      sperm was evaluated by fertility trials. For all studies, sperm viability was
      assessed using the nigrosin-eosin stain. Higher percentages of crane and turkey
      sperm maintained intact membranes when frozen with moderate or slow cooling rates
      compared to rapid cooling rates (P<0.05), regardless of DMA concentration. Turkey
      sperm viability was not affected by thawing rate at any DMA concentration
      (P>0.05). Crane sperm viability was only affected by thawing rate for the 24% DMA
      treatment, where moderate thawing was better than slow thawing (P<0.05). Sperm
      viability was not affected by the semen volume used for freezing for either
      species (P>0.05). The percentage of membrane-intact crane sperm at lower DMA
      concentrations was improved by addition of 0.1M sucrose (P<0.05) but not 0.29 M
      NaCl. The mean fertility rate from frozen/thawed crane semen was 57.5%, and 71.4%
      of the fertile eggs hatched. The viability of crane sperm was always greater than
      turkey sperm, regardless of cooling rate, thawing rate or volume of semen frozen.
      These data verify avian-specific differences in sperm cryosurvival, further
      emphasize the need for species specific studies to optimize cryopreservation
      protocols.

PMID- 22406424
TI  - Reproductive aspects of male franciscana dolphins (Pontoporia blainvillei) off
      Argentina.
AB  - As the first study to investigate reproductive aspects of male franciscana
      dolphin -Pontoporia blainvillei - in Argentine waters, the aim of this paper was
      to assess sexual maturity by using histological and morphometric methods. P.
      blainvillei was labeled as "Vulnerable" by the IUCN in 2008. The specimens
      analyzed were either incidentally caught in artisanal fishing nets (n=47) or
      found stranded on the beach (n=3). Testis weight and testicular index of maturity
      were reliable indicators of sexual maturity, being their values: MTW: 1.14 +/-
      0.60-4.49 +/- 1.94; IM: 0.03 +/- 0.01-0.09 +/- 0.03, for immature and mature
      specimens' respectively. It was found that the hierarchical cluster analysis
      (HCA) might be appropriate for establishing sexual maturity stage, based on both
      the body morphometric measurements and age. The values for age, standard length
      and total weight at attainment sexual maturity were 2.92-3.54 years, 126.19
      126.27 cm and 23.47-23.75 kg. Considering the extremely low relative testis
      weight, the reversed sexual length dimorphism, the absence of secondary sexual
      characteristics, and the lack of scars from intrasexual combats in males, the
      hypothesis that sperm competition does not occur in the species, and male combats
      for accessing female reproductive may be rare for P. blainvillei is reinforced.
      All these features fit the species within a serial monogamous mating system.

PMID- 22406425
TI  - Nanoparticle-based adjuvant for enhanced protective efficacy of DNA vaccine Ag85A
      ESAT-6-IL-21 against Mycobacterium tuberculosis infection.
AB  - The goal of this study was to evaluate the protective efficacy of a cationic
      nanoparticle-based DNA vaccine expressing antigen 85A (Ag85A) and 6-kDa early
      secretory antigen target (ESAT-6) of Mycobacterium tuberculosis as well as
      cytokine interleukin-21 (IL-21) against M. tuberculosis infection. The results of
      this indicated that the anti-M. tuberculosis immune responses were induced in
      mice that had received the different DNA vaccines. More importantly, compared
      with using DNA vaccine Ag85A-ESAT-6-IL-21 alone, the nanoparticle-based DNA
      vaccine Ag85A-ESAT-6-IL-21 showed a statistically significant increase in the
      protective efficacy against M. tuberculosis infection in the immunized mice. We
      concluded that the nanoparticle-based DNA vaccine induced a strong immune
      response and markedly inhibited the growth of the M. tuberculosis in the mice.
      These findings highlighted the potential utility of Fe3O4-Glu-polyethyleneimine
      nanoparticles encapsulated with the DNA vaccine as a prophylactic vaccine in the
      M. tuberculosis-infected mouse model. FROM THE CLINICAL EDITOR: This study
      emphasizes the potential utility of Fe3O4-Glu-polyethyleneimine nanoparticles
      encapsulated with DNA vaccine against TB as a prophylactic vaccine. The authors
      demonstrated a strong immune response and marked growth inhibition of
      mycobacterium tuberculosis in the mice.

PMID- 22406426
TI  - Effect of an oral astaxanthin prodrug (CDX-085) on lipoprotein levels and
      progression of atherosclerosis in LDLR(-/-) and ApoE(-/-) mice.
AB  - Oxidative stress and inflammation are key promoters of atherosclerosis and
      myocardial damage. When orally administered, the novel astaxanthin prodrug CDX
      085 delivers high levels of the xanthophyll antioxidant astaxanthin that protects
      LDL from oxidation and reduces primary thrombosis. In this study, we analyzed
      whether delivery of astaxanthin from administration of the CDX-085 prodrug
      reduces plasma lipoprotein levels and the progression of atherosclerosis in low
      density lipoprotein receptor negative (LDLR(-/-)) and apolipoprotein E deficient
      (ApoE(-/-)) mice. METHODS: Relative circulating levels of astaxanthin derived
      from CDX-085 administration compared to administration of pure astaxanthin was
      initially evaluated in a canine model. In mouse Study #1, 16 wild-type and 16
      LDLR(-/-) mice on 0.5% cholesterol diet supplemented with either 0.0%, 0.08%,
      0.2% and 0.4% CDX-085 were used to assess plasma levels and lipoprotein
      biodistribution measured by FPLC after 4 weeks treatment. In Study #2, 36 male
      LDLR(-/-) mice were randomized to a 0.5% cholesterol chow diet (CHOW group, n=12)
      or 0.5% cholesterol chow fortified with 0.08% CDX-085 (n=12) or 0.5% cholesterol
      chow with 0.4% CDX-085 (n=12) for 12 weeks. In Study #3, 34 male ApoE(-/-) mice
      were randomized in the same fashion as the Study #2 and fed similar diets for 9
      weeks. RESULTS: CDX-085 administration was shown to result in significantly
      higher levels of circulating astaxanthin (p<0.001 ANOVA) over a 72 h period
      compared to pure, non-esterified astaxanthin in a single-dose pharmacokinetic
      study in beagles. In Study #1, plasma astaxanthin levels were 5-9-fold higher in
      LDLR(-/-) mice compared to wild-type mice. Astaxanthin was highly distributed
      among all lipoprotein fractions, generally reflecting cholesterol content of
      lipoproteins. In Study #2, administration of CDX-085 resulted in significantly
      lower total cholesterol levels (528+/-68 mg/dL vs. 550+/-67 mg/dL vs. 602+/-80
      mg/dL, p=0.047) and aortic arch atherosclerosis (9.0+/-4.2% vs. 9.8+/-3.5% vs.
      13.2+/-3.6%, p=0.023) in the 0.4% CDX-085 group compared to the 0.08% CDX-085 and
      CHOW groups, respectively. In ApoE(-/-) mice, a 72% reduction in triglycerides in
      the 0.4% CDX-085 group and 50% reduction in the 0.08% CDX-085 groups was noted
      compared to CHOW group (final levels 17+/-11 mg/dL vs. 30+/-15 mg/dL vs. 60+/-32
      mg/dL, respectively, p=0.001). CONCLUSION: Oral administration of the novel
      astaxanthin prodrug CDX-085 shows that it distributes among lipoproteins. CDX-085
      lowers total cholesterol and aortic arch atherosclerosis in LDLR(-/-) mice and
      triglyceride levels in ApoE(-/-) mice and shows promise for further evaluation in
      human studies.

PMID- 22406427
TI  - Secreted phospholipase A(2) group IIA is a neurotoxin released by stimulated
      human glial cells.
AB  - Neuroinflammation, which is one of the hallmarks of neurodegenerative disorders
      such as Alzheimer's disease, involves secretion of pro-inflammatory mediators by
      activated glial cells. Secreted phospholipase A(2) group IIA (sPLA(2)IIA) has
      been implicated as an inflammatory mediator contributing to various peripheral
      inflammatory conditions; however, little is known about the role this enzyme
      plays in neuroinflammation. Human microglia-like promonocytic THP-1 cells and
      human primary astrocytes were used to study sPLA(2)IIA expression, secretion and
      function. Production of sPLA(2)IIA by these cells was induced in response to
      stimulation by pro-inflammatory mediators at both mRNA and protein levels.
      Removal of sPLA(2)IIA from stimulated human microglia-like cell and astrocyte
      supernatants by immunosorbent caused significant reduction of their toxicity
      towards SH-SY5Y neuroblastoma cells. Both sPLA(2)IIA specific and non-specific
      PLA(2) inhibitors exhibited no anti-cytotoxic or neuroprotective effects,
      suggesting that sPLA(2)IIA cytotoxicity is mediated by a non-enzymatic mechanism.
      The data obtained indicate that sPLA(2)IIA may contribute to the pathogenesis of
      neurodegenerative diseases involving neuroinflammation. Agents inhibiting the non
      enzymatic actions of sPLA(2)IIA could be used to slow down progression of
      neurodegenerative processes that are driven by inflammation.

PMID- 22406428
TI  - Ankyrin-B reduction enhances Ca spark-mediated SR Ca release promoting cardiac
      myocyte arrhythmic activity.
AB  - Ankyrin-B (AnkB) loss-of-function may cause ventricular arrhythmias and sudden
      cardiac death in humans. Cardiac myocytes from AnkB heterozygous mice (AnkB(+/-))
      show reduced expression and altered localization of Na/Ca exchanger (NCX) and
      Na/K-ATPase (NKA), key players in regulating [Na](i) and [Ca](i). Here we
      investigate how AnkB reduction affects cardiac [Na](i), [Ca](i) and SR Ca
      release. We found reduced NCX and NKA transport function but unaltered [Na](i)
      and diastolic [Ca](i) in myocytes from AnkB(+/-) vs. wild-type (WT) mice. Ca
      transients, SR Ca content and fractional SR Ca release were larger in AnkB(+/-)
      myocytes. The frequency of spontaneous, diastolic Ca sparks (CaSpF) was
      significantly higher in intact myocytes from AnkB(+/-) vs. WT myocytes (with and
      without isoproterenol), even when normalized for SR Ca load. However, total
      ryanodine receptor (RyR)-mediated SR Ca leak (tetracaine-sensitive) was not
      different between groups. Thus, in AnkB(+/-) mice SR Ca leak is biased towards
      more Ca sparks (vs. smaller release events), suggesting more coordinated openings
      of RyRs in a cluster. This is due to local cytosolic RyR regulation, rather than
      intrinsic RyR differences, since CaSpF was similar in saponin-permeabilized
      myocytes from WT and AnkB(+/-) mice. The more coordinated RyRs openings resulted
      in an increased propensity of pro-arrhythmic Ca waves in AnkB(+/-) myocytes. In
      conclusion, AnkB reduction alters cardiac Na and Ca transport and enhances the
      coupled RyR openings, resulting in more frequent Ca sparks and waves although the
      total SR Ca leak is unaffected. This could enhance the propensity for triggered
      arrhythmias in AnkB(+/-) mice.

PMID- 22406430
TI  - A functional dual-coated (FDC) microtiter plate method to replace the botulinum
      toxin LD50 test.
AB  - Conventional capture ("Sandwich") ELISAs equally detect denatured inactive and
      native active botulinum type A toxin. Light chain endoprotease activity assays
      also fail to distinguish between various inactive molecules including partially
      denatured and fragmented material still retaining this protease activity. By co
      coating microtiter plates with SNAP25 substrate and a monoclonal antibody
      specific for a conformational epitope of the toxin's Hc domain, it was possible
      to develop a highly sensitive (130 aM LoD), precise (1.4% GCV) new assay specific
      for the biologically active toxin molecule. Capture was performed in phosphate
      buffer with a fixed optimal concentration of chaotropic agent (e.g., 1.2 M urea)
      to differentially isolate functional toxin molecules. Addition of enzymatically
      favorable buffer containing zinc and DTT reduced the interchain disulfide bond
      releasing and activating the captured L-chain with subsequent specific cleavage
      of the SNAP25(1-206) substrate. A neoepitope antibody specific for the newly
      exposed Q(197) epitope was used to quantify the cleaved SNAP25(1-197). The
      assay's requirement for the intact toxin molecule was demonstrated with pre
      reduced toxin (heavy and light chains), recombinant LHn fragments, and stressed
      samples containing partially or fully denatured material. This is the first known
      immunobiochemical assay that correlates with in vivo potency and provides a
      realistic alternative.

PMID- 22406429
TI  - Mitochondrial permeability transition in the diabetic heart: contributions of
      thiol redox state and mitochondrial calcium to augmented reperfusion injury.
AB  - Mitochondria from diabetic hearts are sensitized to mitochondrial permeability
      transition pore (PTP) opening, which may be responsible for the increased
      propensity for cardiac injury in diabetic hearts. The purpose of this study was
      to determine if redox-dependent PTP opening contributes to augmented injury in
      diabetic hearts, and if compounds targeted at mitochondrial PTP, ROS, and calcium
      influx protected diabetic hearts from injury. Hearts from control or
      streptozotocin-induced diabetic rats were excised for either whole-heart or
      isolated mitochondria experiments. Myocardial glutathione content was oxidized in
      diabetic hearts when compared to control, and this translated to increased
      oxidation of the adenine nucleotide translocase in diabetic hearts. Diabetic
      mitochondria displayed significantly greater sensitivity to PTP opening than non
      diabetic counterparts, which was reversed with the thiol-reducing agent
      dithiothreitol. The thiol-oxidant diamide increased calcium sensitivity in
      control, but not diabetic mitochondria. Diabetic animals treated with the
      mitochondria-targeted ROS suppressing peptide MTP-131 also showed improved
      resistance to PTP opening. In separate experiments hearts underwent ex vivo
      ischemia/reperfusion (IR). Diabetic hearts were more susceptible to IR injury,
      with infarct sizes of 60 +/- 4% of the area-at-risk (vs. 46 +/- 2% in non
      diabetics; P<0.05). Administration of the PTP blocker NIM811 (5 MUM), MTP-131 (1
      nM) or the mitochondrial calcium uniporter blocker minocycline (1 MUM) at the
      onset of reperfusion reduced infarct sizes in both control and diabetic hearts.
      These findings suggest that augmented susceptibility to injury in the diabetic
      heart is mediated by redox-dependent shifts in PTP opening, and that three novel
      mitochondria-targeted agents administered at reperfusion may be suitable adjuvant
      reperfusion therapies to attenuate injury in diabetic patients.

PMID- 22406431
TI  - Ultra-fast pg/ml anthrax toxin (protective antigen) detection assay based on
      microwave-accelerated metal-enhanced fluorescence.
AB  - Rapid presymptomatic diagnosis of Bacillus anthracis at early stages of infection
      plays a crucial role in prompt medical intervention to prevent rapid disease
      progression and accumulation of lethal levels of toxin. To detect low levels of
      the anthrax protective antigen (PA) exotoxin in biological fluids, we have
      developed a metal-enhanced fluorescence (MEF)-PA assay using a combination of the
      MEF effect and microwave-accelerated PA protein surface absorption. The assay is
      based on a modified version of our "rapid catch and signal" (RCS) technology
      previously designed for the ultra-fast and sensitive analysis of genomic DNA
      sequences. Technologically, the proposed MEF-PA assay uses standard 96-well
      plastic plates modified with silver island films (SiFs) grown within the wells.
      It is shown that the fluorescent probe, covalently attached to the secondary
      antibody, plays a crucial role of indicating complex formation (i.e., shows a
      strong MEF response to the recognition event). Microwave irradiation rapidly
      accelerates PA deposition onto the surface ("rapid catch"), significantly
      speeding up the MEF-PA assay and resulting in a total assay run time of less than
      40 min with an analytical sensitivity of less than 1 pg/ml PA.

PMID- 22406432
TI  - Evaluation of 2,6-dihydroxyacetophenone as matrix-assisted laser
      desorption/ionization matrix for analysis of hydrophobic proteins and peptides.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is
      widely used for analysis of macromolecules like peptides and proteins. The
      analysis procedure is generally simple but must be adapted to the characteristics
      of the analytes. Therefore, specific matrices suitable for, e.g., hydrophobic
      proteins and peptides that are difficult to analyze would be preferable in order
      to optimize the outcome. In the present work, 2,6-dihydroxyacetophenone (DHAP)
      was shown to be beneficial in comparison to DHB for intact bacteriorhodopsin (BR)
      as well as for chemically digested BR.

PMID- 22406433
TI  - Toward engineering functional organ modules by additive manufacturing.
AB  - Tissue engineering is emerging as a possible alternative to methods aimed at
      alleviating the growing demand for replacement tissues and organs. A major pillar
      of most tissue engineering approaches is the scaffold, a biocompatible network of
      synthetic or natural polymers, which serves as an extracellular matrix mimic for
      cells. When the scaffold is seeded with cells it is supposed to provide the
      appropriate biomechanical and biochemical conditions for cell proliferation and
      eventual tissue formation. Numerous approaches have been used to fabricate
      scaffolds with ever-growing complexity. Recently, novel approaches have been
      pursued that do not rely on artificial scaffolds. The most promising ones utilize
      matrices of decellularized organs or methods based on multicellular self
      assembly, such as sheet-based and bioprinting-based technologies. We briefly
      overview some of the scaffold-free approaches and detail one that employs
      biological self-assembly and bioprinting. We describe the technology and its
      specific applications to engineer vascular and nerve grafts.

PMID- 22406434
TI  - Dietary inorganic nitrate mobilizes circulating angiogenic cells.
AB  - Nitric oxide (NO) was implicated in the regulation of mobilization and function
      of circulating angiogenic cells (CACs). The supposedly inert anion nitrate,
      abundant in vegetables, can be stepwise reduced in vivo to form nitrite, and
      consecutively NO, representing an alternative to endogenous NO formation by NO
      synthases. This study investigated whether inorganic dietary nitrate influences
      mobilization of CACs. In a randomized double-blind fashion, healthy volunteers
      ingested 150 ml water with 0.15 mmol/kg (12.7 mg/kg) of sodium nitrate, an amount
      corresponding to 100-300 g of a nitrate-rich vegetable, or water alone as
      control. Mobilization of CACs was determined by the number of CD34(+)/KDR(+) and
      CD133(+)/KDR(+) cells using flow cytometry and the mobilization markers stem cell
      factor (SCF) and stromal cell-derived factor-1a (SDF-1alpha) were determined in
      plasma via ELISA. Nitrite and nitrate were measured using high-performance liquid
      chromatography and reductive gas-phase chemiluminescence, respectively. NOS
      dependent vasodilation was measured as flow-mediated vasodilation. Further
      mechanistic studies were performed in mice after intravenous application of
      nitrite together with an NO scavenger to identify the role of nitrite and NO in
      CAC mobilization. Nitrate ingestion led to a rise in plasma nitrite together with
      an acute increase in CD34(+)/KDR(+) and CD133(+)/KDR(+)-CACs along with increased
      NOS-dependent vasodilation. This was paralleled by an increase in SCF and SDF
      1alpha and the maximal increase in plasma nitrite correlated with CD133(+)/KDR(+)
      CACs (r=0.73, P=0.016). In mice, nitrate given per gavage and direct intravenous
      injection of nitrite led to CAC mobilization, which was abolished by the NO
      scavenger cPTIO, suggesting that nitrite mediated its effect via formation of NO.
      Dietary inorganic nitrate acutely mobilizes CACs via serial reduction to nitrite
      and NO. The nitrate-nitrite-NO pathway could offer a novel nutritional approach
      for regulation of vascular regenerative processes.

PMID- 22406435
TI  - Activation of thromboxane receptor modulates interleukin-1beta-induced monocyte
      adhesion--a novel role of Nox1.
AB  - Activation of thromboxane receptors (TPr) may promote atherosclerosis by
      enhancing oxidative stress and inflammation. This study examined the role of
      Nox1, an NADPH-oxidase subunit, in the enhancement of interleukin (IL)-1beta
      induced monocyte adhesion by TPr. In cultured rat aortic vascular smooth muscle
      cells (VSMCs), U46619, a stable thromboxane A(2) mimetic, together with
      interleukin-1beta significantly enhanced Nox1 mRNA expression, as well as
      adhesion of THP-1 monocytes. Activation of TPr also enhanced IL-1beta-induced
      vascular cell adhesion molecule (VCAM)-1 expression, but inhibited inducible
      nitric oxide synthase (iNOS) expression. Silencing Nox1 expression by siRNA
      prevented the U46619 enhancement of IL-1beta-induced monocyte adhesion, but had
      no significant effect on VCAM-1 or iNOS expression. Furthermore, monocyte
      adhesion was inhibited by superoxide dismutase, enhanced by a specific iNOS
      inhibitor, l-N(6)-(1-iminoethyl)-lysine, but not influenced by catalase. U46619
      inhibited IL-1beta-induced cyclic GMP production, and the inhibition was
      partially prevented by superoxide dismutase. In conclusion, activation of TPr
      enhances IL-1beta-induced Nox1 expression in VSMCs, which is responsible for the
      up-regulation of monocyte adhesion. The effect of Nox1 is independent of the
      changes in VCAM-1 and iNOS expression, but depends on the inactivation of nitric
      oxide via generation of superoxide anion.

PMID- 22406436
TI  - Validation of a GyrolabTM assay for quantification of rituximab in human serum.
AB  - INTRODUCTION: GyrolabTM technology presents a technology breakthrough for large
      molecule bioanalysis to support biologic drug development. The advantages of this
      innovative platform include fully automated nanoscale immunoassay capability,
      better assay reproducibility and data quality, small reagent and sample volumes,
      and rapid assay development and validation as a result of reduced run time.
      Although Gyrolab has been increasingly used in method development in discovery
      environment, few fully validated Gyrolab assays have been reported. Here we
      report a method validation of a Gyrolab assay to determine rituximab levels in
      human serum. METHODS: Rituximab is captured on a BioaffyTM CD by a biotinylated
      rat anti-idiotypic monoclonal antibody against rituximab and detected by an Alexa
      Fluor(r)-labeled anti-human IgG antibody. Assay conditions were optimized to give
      required sensitivity and dynamic range. The assay validation was conducted
      according to the current industry standards for GLP-regulated immunoassays.
      RESULTS: The intrabatch precision and accuracy for the assay were determined
      using spiked human serum samples and shown to have a coefficient of variation
      (CV) of <11% with a mean bias <20%. The interbatch precision (CV) and absolute
      mean bias were both <12% with the total error <25%. Adequate spike recovery was
      demonstrated in serum samples of healthy individuals and solid tumor patients.
      The dilutional linearity test showed that the determined concentrations adjusted
      with various dilution factors had a linear relationship with the expected
      concentrations and that there was no hook effect. The method has been validated
      for the quantification of rituximab in human serum from 90 to 60,000 ng/mL with a
      minimum required dilution of 30. DISCUSSION: The Gyrolab assay was proved to be
      accurate, precise and selective, with a comparable sensitivity to the ELISA
      method, but provided an automated nanoscale assay with a significantly wider
      assay dynamic range for the determination of rituximab in human serum during
      pharmacokinetics/toxicokinetics studies.

PMID- 22406438
TI  - Vitamin D compounds and diabetic nephropathy.
AB  - Vitamin D therapies for renal disease have been used for over a half century and
      are likely to be utilized for many more years. Past roles have been to alter
      calcium and phosphorus metabolism to prevent or lessen bone disease and reduce
      PTH levels in dialysis patients and more recently, pre-dialysis patients.
      However, emerging evidence indicates new applications for vitamin D compounds are
      likely to exist for this patient population. In addition to the possible new
      targets in this therapeutic area, a popularly debated topic is the ideal form of
      vitamin D for use in renal disease. Because the vitamin D metabolism system is
      severely altered in kidney disease, a thorough understanding of the disease
      progression relative to the vitamin D signaling pathway is necessary. The current
      state of knowledge in this area with the primary focus on patients with diabetic
      nephropathy will be the scope of this review.

PMID- 22406437
TI  - Protective role for ovarian glutathione S-transferase isoform pi during 7,12
      dimethylbenz[a]anthracene-induced ovotoxicity.
AB  - 7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles at all
      developmental stages. This study investigated a role for the glutathione S
      transferase (Gst) isoforms alpha (a), mu (m) and pi (p) and the transcription
      factors, Ahr and Nrf2, during DMBA-induced ovotoxicity, and their regulation by
      phosphatidylinositol-3 kinase (PI3K) signaling. Negative regulation of JNK by
      GSTP during DMBA exposure was also studied. Post-natal day (PND) 4 Fischer 344
      rat ovaries were exposed to vehicle control (1% DMSO)+/-DMBA (1 MUM) or vehicle
      control (1% DMSO)+/-LY294002 (PI3K inhibitor; 20 MUM) for 1, 2, 4, or 6 days.
      Total RNA or protein was isolated, followed by RT-PCR or Western blotting to
      determine mRNA or protein level, respectively. Immunoprecipitation using an anti
      GSTP antibody was performed to determine interaction between GSTP and JNK,
      followed by Western blotting to determine JNK and p-c-Jun protein level. DMBA had
      no impact on Gsta, Gstm or Nrf2 mRNA level, but increased Gstp mRNA and protein
      after 2 days. Ahr mRNA and protein increased after 2 and 4 days of DMBA exposure,
      respectively and DMBA increased NRF2 protein level after 4 days. JNK bound to
      GSTP was increased during DMBA exposure, with a concomitant decrease in unbound
      JNK and p-c-Jun. Ahr and Gstp mRNA were decreased (2 days) and increased (4 days)
      by PI3K inhibition, while Gstm mRNA increased (P<0.05) after both time points,
      and there was no effect on Nrf2 mRNA. PI3K inhibition increased AHR, NRF2 and
      GSTP protein level. These findings support involvement of ovarian GSTP during
      DMBA exposure, and indicate a regulatory role for the PI3K signaling pathway on
      ovarian xenobiotic metabolism gene expression.

PMID- 22406439
TI  - Rare but severe concerted punishment that favors cooperation.
AB  - As one of the mechanisms that are supposed to explain the evolution of
      cooperation among unrelated individuals, costly punishment, in which altruistic
      individuals privately bear the cost to punish defection, suffers from such
      drawbacks as decreasing individuals' welfare, inducing second-order free riding,
      the difficulty of catching defection, and the possibility of triggering
      retaliation. To improve this promising mechanism, here we propose an extended
      Public Goods game with rare but severe concerted punishment, in which once a
      defector is caught punishment is triggered and the cost of punishment is equally
      shared among the remainder of the group. Analytical results show that, when the
      probability for concerted punishment is above a threshold, cooperating is, while
      defecting is not, an evolutionarily stable strategy in finite populations, and
      that this way of punishment can considerably decrease the total cost of
      inhibiting defection, especially in large populations.

PMID- 22406441
TI  - Effects of the superoxide dismutase/catalase mimetic EUK-207 in a mouse model of
      Alzheimer's disease: protection against and interruption of progression of
      amyloid and tau pathology and cognitive decline.
AB  - Alzheimer's disease (AD) is characterized by progressive cognitive deficits,
      accumulation of amyloid-beta (Abeta) and intracellular neurofibrillary tangles,
      and neuronal death. Additionally, mitochondrial dysfunction and free radical
      damage are hallmarks of AD brain. Here we set out to define the role of oxidative
      stress in AD pathogenesis and progression by chronically treating 3xTg-AD mice
      with the superoxide dismutase (SOD)/catalase mimetic, EUK-207. Treatment started
      at 4 months before onset of pathology and cognitive deficits, and continued until
      9 months, when the AD phenotype was established. Cognitive performance was
      assessed using fear conditioning, and brain oxidative stress, Abeta, and tau
      pathology were analyzed. At 9 months, 3xTg-AD mice exhibited a decline in
      performance in both contextual and cued fear conditioning, as compared to wild
      type mice. EUK-207-treated 3xTg-AD mice did not display any deficit in fear
      conditioning and exhibited reduced Abeta, tau, and phosphorylated tau
      accumulation in amygdala and hippocampus, as well as brain levels of Abeta42,
      oxidized nucleic acids, and lipid peroxidation. The effects of a 3-month
      treatment after pathology onset at 9 months on cognitive performance, brain
      oxidative stress, Abeta, and tau pathology were also evaluated. EUK-207-treated
      3xTg-AD mice did not display any deficit in fear conditioning and were protected
      against increases in brain levels of oxidized nucleic acids and lipid
      peroxidation; they also had reduced Abeta, tau, and hyperphosphorylated tau
      accumulation in amygdala and hippocampus. Our results confirm a critical role for
      oxidative stress in AD pathogenesis and progression and suggest the potential
      usefulness of EUK-207 in AD treatment.

PMID- 22406440
TI  - Deferiprone reduces amyloid-beta and tau phosphorylation levels but not reactive
      oxygen species generation in hippocampus of rabbits fed a cholesterol-enriched
      diet.
AB  - Accumulation of amyloid-beta (Abeta) peptide and the hyperphosphorylation of tau
      protein are major hallmarks of Alzheimer's disease (AD). The causes of AD are not
      well known but a number of environmental and dietary factors are suggested to
      increase the risk of developing AD. Additionally, altered metabolism of iron may
      have a role in the pathogenesis of AD. We have previously demonstrated that
      cholesterol-enriched diet causes AD-like pathology with iron deposition in rabbit
      brain. However, the extent to which chelation of iron protects against this
      pathology has not been determined. In this study, we administered the iron
      chelator deferiprone in drinking water to rabbits fed with a 2% cholesterol diet
      for 12 weeks. We found that deferiprone (both at 10 and 50 mg/kg/day)
      significantly decreased levels of Abeta40 and Abeta42 as well as BACE1, the
      enzyme that initiates cleavage of amyloid-beta protein precursor to yield Abeta.
      Deferiprone also reduced the cholesterol diet-induced increase in phosphorylation
      of tau but failed to reduce reactive oxygen species generation. While deferiprone
      treatment was not associated with any change in brain iron levels, it was
      associated with a significant reduction in plasma iron and cholesterol levels.
      These results demonstrate that deferiprone confers important protection against
      hypercholesterolemia-induced AD pathology but the mechanism(s) may involve
      reduction in plasma iron and cholesterol levels rather than chelation of brain
      iron. We propose that adding an antioxidant therapy to deferiprone may be
      necessary to fully protect against cholesterol-enriched diet-induced AD-like
      pathology.

PMID- 22406442
TI  - Rates of hemispheric and lobar atrophy in the language variants of frontotemporal
      lobar degeneration.
AB  - Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder which
      presents with either behavioral or language impairment. The two language
      syndromes are known as progressive nonfluent aphasia (PNFA) and semantic dementia
      (SEMD). While cross-sectional imaging patterns of brain atrophy are well
      described in FTLD, fewer studies have investigated longitudinal imaging changes.
      We measured longitudinal hemispheric and lobar atrophy rates using serial MRI in
      a cohort of 18 patients with PNFA and 17 patients with SEMD as well as 14
      cognitively-normal control subjects. We subsequently calculated sample size
      estimates for clinical trials. Rates of left hemisphere atrophy were greater than
      rates of right hemisphere atrophy in both PNFA and SEMD with no significant
      differences between the groups. The disease groups showed asymmetrical atrophy
      (more severe on the left) at baseline with significantly increasing asymmetry
      over time. Within a hemisphere, the fastest rate of atrophy varied between lobes:
      in SEMD temporal > frontal > parietal > occipital, while in PNFA frontal >
      temporal/parietal > occipital. In SEMD, using temporal lobe measures of atrophy
      in clinical trials would provide the lowest sample sizes necessary, while in PNFA
      left hemisphere atrophy measures provided the lowest sample size. These patterns
      provide information about disease evolution in the FTLD language variants that is
      of both clinical and neurobiological relevance.

PMID- 22406443
TI  - A two-year follow-up of cognitive deficits and brain perfusion in mild cognitive
      impairment and mild Alzheimer's disease.
AB  - The 15-Objects Test (15-OT) provides useful gradation of visuoperceptual
      impairment from normal aging through Alzheimer's disease (AD) and correlates with
      temporo-parietal perfusion. The objectives of this study were to analyze
      progression of 15-OT performance in mild cognitive impairment (MCI) and AD, and
      its correlates with cognition and single photon emission computerized tomography
      (SPECT), as well as to examine neuropsychological and SPECT differences between
      the MCI patients who developed AD and those who did not. From the initial 126
      participants (42/group), 38 AD, 39 MCI, and 38 elderly controls (EC) were
      reassessed (SPECT: 35 AD, 33 MCI, 35 EC) after two years. The progression of
      cognitive and SPECT scores during this period was compared between groups, and
      baseline data between converters and non-converters. The 15-OT was the only
      measure of progression that differed between the three groups; worsening scores
      on 15-OT were associated with worsening in verbal and visual retention, and
      decreased perfusion on left postsubicular area. In the MCI patients, cerebral
      perfusion fell over the two years in medial-posterior cingulate and fronto
      temporo-parietal regions; AD showed extensive changes involving almost all
      cerebral regions. No SPECT changes were detected in controls. At baseline, the
      MCI patients who developed AD differed from non-converters in verbal recognition
      memory, but not in SPECT perfusion. In conclusion, SPECT and 15-OT appear to
      provide a potential measure to differentiate between normal aging, MCI, and AD.
      Worsening on 15-OT was related to decreased perfusion in postsubicular area; but
      further longitudinal studies are needed to determine the contribution of 15-OT as
      a predictor of AD from MCI.

PMID- 22406444
TI  - Metabolism and neurotoxicity of homocysteine thiolactone in mice: evidence for a
      protective role of paraoxonase 1.
AB  - Homocysteine (Hcy)-thiolactone is toxic, induces epileptic seizures in rodents,
      and has been implicated in Alzheimer's disease. Paraoxonase 1 (Pon1), a component
      of high-density lipoprotein, hydrolyzes Hcy-thiolactone in vitro. Whether this
      reflects a physiological function and whether Pon1 can protect against Hcy
      thiolactone toxicity was unknown. Here we show that Hcy-thiolactone was elevated
      in brains of Pon1-/- mice (1.5-fold, p = 0.047) and that Pon1-/- mice excrete
      more Hcy-thiolactone than wild type animals (2.4-fold, p = 0.047). The frequency
      of seizures induced by intraperitoneal injections of L-Hcy-thiolactone was
      significantly higher in Pon1-/- mice compared with wild type animals (52.8%
      versus 29.5%, p = 0.042); the latency of seizures was lower in Pon1-/- mice than
      in wild type animals (31.8 min versus 41.2 min, p = 0.019). Using the Pon1 null
      mice, we provide the first direct evidence that a specific Hcy metabolite, Hcy
      thiolactone, rather than Hcy itself is neurotoxic in vivo. Our findings indicate
      that Pon1 protects mice against Hcy-thiolactone neurotoxicity by hydrolyzing it
      in the brain, and suggest a mechanism by which Pon1 can protect against
      neurodegeneration associated with hyperhomocysteinemia and Alzheimer's disease.

PMID- 22406445
TI  - Systematic evaluation of magnetic resonance imaging and spectroscopy techniques
      for imaging a transgenic model of Alzheimer's disease (AbetaPP/PS1).
AB  - Murine models of Alzheimer's disease (AD) provide means to detect and follow
      biomarker changes similar to those observed in humans. Non-invasive biomarkers,
      such as those provided by magnetic resonance imaging (MRI) and spectroscopy (MRS)
      methods are highly desirable, however, systematic studies of in vivo MRI/MRS
      methods to characterize the cerebral morphology and metabolic pattern of these
      mice remain scarce. We investigated sixteen consecutive slices from the brain of
      wild-type and AbetaPP/PS1 mice, obtaining a collection of T2 weighted, diffusion
      weighted and magnetization transfer weighted images as well as 1H PRESS spectra
      from the cortical and subcortical areas. Compared to controls, AbetaPP/PS1 mice
      show significant regional hyperintensities in T2 weighted images of the cerebral
      cortex, significant ventricular enlargement, and decreased hippocampal area and
      fractional magnetization transfer. MRS demonstrated an increase in the ratio of
      choline (Cho) to creatine (Cr) in the cortical and subcortical areas of the
      transgenic animals. A logistic regression classifier was implemented considering
      all parameters investigated, and revealed the most characteristic changes and
      allowed for the correct classification of control and AbetaPP/PS1 mice. In
      summary, the present results provide a useful frame to evaluate optimal MRI/MRS
      biomarkers for the characterization of AD models, potentially applicable in drug
      discovery processes, because of their non-invasive and repeatable nature in
      longitudinal studies.

PMID- 22406446
TI  - Amyloid-beta metabolite sensing: biochemical linking of glycation modification
      and misfolding.
AB  - Glycation is the reaction of a reducing sugar with proteins and lipids, resulting
      in myriads of glycation products, protein modifications, cross-linking, and
      oxidative stress. Glycation reactions are also elevated during metabolic
      dysfunction such as in Alzheimer's disease (AD) and Down's syndrome. These
      reactions increase the misfolding of the proteins such as tau and amyloid-beta
      (Abeta), and colocalize with amyloid plaques in AD. Thus, glycation links
      metabolic dysfunction and AD and may have a causal role in AD. We have
      characterized the reaction of Abeta with reactive metabolites that are elevated
      during metabolic dysfunction. One metabolite, glyceraldehyde-3-phosphate, is a
      normal product of glycolysis, while the others are associated with pathology. Our
      data demonstrates that lipid oxidation products malondialdehyde, hydroxynonenal,
      and glycation metabolites (methylglyoxal, glyceraldehyde, and glyceraldehyde-3
      phosphate) modify Abeta42 and increase misfolding. Using mass spectrometry,
      modifications primarily occurred at the amino terminus. However, the metabolite
      methylglyoxal modified Arg5 in the Abeta sequence. 4-Hydroxy-2-nonenal
      modifications were similar to our previous publication. To place such
      modifications into an in vivo context, we stained AD brain tissue for endproducts
      of glycation, or advanced glycation endproducts (AGE). Similar to previous
      findings, AGE colocalized with amyloid plaques. In summary, we demonstrate the
      glycation of Abeta and plaques by metabolic compounds. Thus, glycation
      potentially links metabolic dysfunction and Abeta misfolding in AD, and may
      contribute to the AD pathogenesis. This association can further be expanded to
      raise the tantalizing concept that such Abeta modification and misfolding can
      function as a sensor of metabolic dysfunction.

PMID- 22406447
TI  - Evidence that the amyloid-beta protein precursor intracellular domain, AICD,
      derives from beta-secretase-generated C-terminal fragment.
AB  - One of the major pathological hallmarks of brains affected with Alzheimer's
      disease (AD) is the senile plaque, an extracellular deposit mainly composed of a
      set of highly insoluble peptides of various lengths (39-43 amino acids) referred
      to as amyloid-beta (Abeta) peptides. Abeta peptides are derived from combined
      proteolytic cleavages undergone on the amyloid-beta protein precursor (AbetaPP)
      by a set of enzymes called secretases. Several lines of anatomical and biological
      evidence suggest that Abeta peptides would not account for all pathological
      stigmata and molecular dysfunctions taking place in AD. In amyloidogenic and non
      amyloidogenic pathways, AbetaPP first undergoes beta- or alpha-secretases
      mediated cleavages yielding C99 and C83, respectively. These two membrane
      embedded C-terminal fragments are both potential targets of subsequent gamma
      secretase-mediated proteolysis. The latter cleavage not only generates either p3
      or Abeta peptides but similarly gives rise to an AbetaPP IntraCellular Domain
      (AICD fragment) that could modulate the transcription of several genes linked to
      AD pathology. It is therefore striking that AICD theoretically derives from both
      amyloidogenic and non-amyloidogenic AbetaPP processing pathways. Here we show
      that AICD predominantly derives from C99 by means of recombinant substrates and
      transiently transfected cells expressing C99. Our data suggest a preferred
      pathogenic pathway for AICD production and suggests that this fragment, in
      addition to C99 and Abeta peptides, could contribute to AD pathology.

PMID- 22406448
TI  - Reduced inflammatory response to Aeromonas salmonicida infection in common carp
      (Cyprinus carpio L.) fed with beta-glucan supplements.
AB  - The objective of the present study was to determine the action of beta-glucans as
      feed additives on the gene expression profile of some inflammatory-related
      cytokines from common carp (Cyprinus carpio L.) during the early stages of a non
      lethal bacterial infection with Aeromonas salmonicida. beta-glucan
      (MacroGard((r))), was administered daily to carp (6 mg per kg body weight) in the
      form of supplemented commercial food pellets for 14 days prior to infection.
      Control and treated fish were then intraperitoneally injected with PBS or 4*10(8)
      bacteria per fish and were sampled at time 0 and 6h, 12h, 1 day, 3 days and 5
      days post-injection. Head kidney and gut were collected and the gene expression
      patterns for tnfalpha1, tnfalpha2, il1beta, il6 and il10 were analyzed by
      quantitative PCR. Results obtained showed that treatment with beta-glucans
      generally down-regulated the expression of all measured genes when compared to
      their corresponding controls. After injection, highest changes in the gene
      expression levels were obtained at 6h; particularly, in head kidney there was
      higher up-regulation of tnfa1 and tnfa2 in infected fish fed beta-glucans in
      comparison to control feed; however, in gut there was a significant down
      regulation of tnfalpha1, tnfalpha2, il1beta and il6 in infected fish fed beta
      glucans. Analysis of carp specific antibodies against A. salmonicida 30 days
      after injection revealed their levels were reduced in the infected beta-glucan
      group. In conclusion, a diet supplemented with beta-glucan (MacroGard((r)))
      reduced the gene expression levels of some inflammation-related cytokines in
      common carp. Such a response appears to be dependent of organ studied and
      therefore the immunostimulant may be preventing an acute and potential dangerous
      response in gut, whilst enhancing the inflammatory response in head kidney when
      exposed to A. salmonicida.

PMID- 22406449
TI  - Blocking the large extracellular loop (LEL) domain of FcTetraspanin-3 could
      inhibit the infection of white spot syndrome virus (WSSV) in Chinese shrimp,
      Fenneropenaeus chinensis.
AB  - Tetraspanins belong to the transmembrane 4 superfamily (TM(4)SF), which span the
      cell membrane 4 times and act as bridges or connectors. Increasing evidences have
      shown that tetraspanins play important role in virus infection. The large
      extracellular loop (LEL) of a tetraspanin is considered as a possible target of
      some virus. Tetraspanins are widely found in invertebrates, but the functional
      roles of most invertebrate tetraspanins have remained unknown. Recently, a
      tetraspanin, called FcTetraspanin-3, was cloned from the cDNA library of Chinese
      shrimp, Fenneropenaeus chinensis. The FcTetraspanin-3 constitutive expression in
      all examined tissues and the expression of the gene were highly induced in
      hepatopancreas, lymphoid organ and intestine by white spot syndrome virus (WSSV)
      challenge. In this study, we expressed and purified the recombinant peptide
      containing the LEL domain of FcTetraspanin-3, and produced the anti-LEL polyclone
      antibody. The expression of FcTetraspanin-3 was observed by real-time PCR and
      Western blot. Also, the localization of FcTetraspanin-3-positive cells in
      intestine and hepatopancreas were revealed by immunofluorescence. The results of
      anti-LEL antibody blocking experiments shown that the antibody can significantly
      reduce the mortality of shrimp challenged by WSSV. Additionally, dsRNA
      interference was utilized to examine the functional role of FcTetraspanin-3 in
      response to WSSV infection, and a sensible decrease of the viral copy number in
      the tetraspanin knockdown shrimp. These results suggested the blocking of LEL
      domain of FcTetraspanin-3 could inhibit the infection of WSSV. FcTetraspanin-3
      might play an important role in response to WSSV infection, and the LEL domain of
      FcTetraspanin-3 might mediate the entry of WSSV.

PMID- 22406450
TI  - Rapid and cost-effective baculovirus sample preparation method as a viable
      alternative to conventional preparation for quantitative real-time PCR.
AB  - The increasing use of the baculovirus expression vector system (BEVS) has
      generated significant interest into techniques for quantifying baculovirus
      stocks. One method involves the use of quantitative real-time polymerase chain
      reaction (PCR). This study investigated simplifying baculovirus sample
      preparation for quantitative Real Time PCR to provide an alternative to current
      kit-based preparation methods. To achieve this goal, combinations of freeze/thaw
      cycles and Triton X-100 treatment were investigated. A treatment with only Triton
      X-100 was found to be sufficient to provide a simple, rapid and cheap alternative
      to kit-based preparation methods. This study also examined other factors such as
      primer choice to further examine the process of baculovirus quantitation by qPCR.

PMID- 22406451
TI  - New cytotoxic quinolone alkaloids from fruits of Evodia rutaecarpa.
AB  - Three new quinolone alkaloids, 1-methyl-2-[7-hydroxy-(E)-9-tridecenyl]-4(1H)
      quinolone (1), 1-methyl-2-[(Z)-4-nonenyl]-4(1H)-quinolone (2), 1-methyl-2
      [(1E,5Z)-1,5-undecadienyl]-4(1H)-quinolone (3) and one new natural product, 1
      methyl-2-[(E)-1-undecenyl]-4(1H)-quinolone (4), were isolated from the dried and
      nearly ripe fruits of Evodia rutaecarpa (Juss.) Benth., along with thirteen known
      compounds (5-17). In addition, one new artificial product, 1-methyl-2-[7-carbonyl
      (E)-9-tridecenyl]-4(1H)-quinolone (1A) was also obtained. The structures of these
      compounds were determined by spectroscopic analyses. The cytotoxic activities of
      all of the compounds against the human cancer cell lines HL-60, N-87, H-460, and
      Hep G(2) cells were evaluated by MTT assay. The results showed that these
      alkaloids inhibited cell proliferation with IC(50) values between 14MUM and
      22MUM.

PMID- 22406453
TI  - Isorhynchophylline: A plant alkaloid with therapeutic potential for
      cardiovascular and central nervous system diseases.
AB  - Uncaria species (Gouteng in Chinese) have been used as a plant medicine to treat
      ailments of cardiovascular and central nervous systems. As the main alkaloid
      constituent of Uncaria species, isorhynchophylline has drawn extensive attention
      toward antihypertensive and neuroprotective activities in recent years.
      Isorhynchophylline mainly acts on cardiovascular and central nervous systems
      diseases including hypertension, brachycardia, arrhythmia, and sedation, vascular
      dementia, and amnesia. Isorhynchophylline also has effects on anticoagulation,
      inhibition vascular smooth muscle cell apoptosis and proliferation, anti
      multidrug resistant of lung cells, anti-endotoxemic, and antispasmodic. The
      active mechanisms are related to modulation on calcium ion channel, protection
      neural and neuroglial cells against beta-amyloid(25-35)-induced neurotoxicity and
      via inducing autophagy. As a candidate drug of several cardiovascular and central
      nervous systems diseases, isorhynchophylline will attract scientists to pursue
      the potential related pharmacological effects and its mechanism with new
      technologies. But relatively few clinical application of isorhynchophylline has
      been conducted on its pharmacological activities. It requires more in vivo
      validations and further investigations of antihypertensive and neuroprotective
      mechanisms of isorhynchophylline.

PMID- 22406452
TI  - The novel Sinupret(r) dry extract exhibits anti-inflammatory effectiveness in
      vivo.
AB  - Sinupret(r) is frequently used as a herbal medicinal product to treat sinusitis,
      and it was assumed that anti-inflammatory effects might contribute to its overall
      beneficial properties. Here, we investigated the effects of a Sinupret(r) drug
      mixture (SIN) as well as of the novel Sinupret(r) dry extract (SIN DE) with the
      latter containing higher concentrations of active ingredients, in an in vivo
      model of acute inflammation, the carrageenan-induced pleurisy in rats. Both SIN
      and SIN DE were administered to rats orally at doses of 100mg/kg (low dose) and
      500mg/kg (high dose) 1h prior to intrapleural injection of carrageenan. Although
      both SIN and SIN DE significantly reduced the exudate volume and leukocyte
      numbers in the pleural exudate at the high and the low dose 4h after carrageenan
      injection, the novel SIN DE was more efficient than SIN at the low dose, implying
      higher efficiency. In parallel, the novel dry extract SIN DE, but not SIN, at
      500mg/kg significantly lowered the levels of prostaglandin (PG)E(2) in the
      exudates and reduced the amounts of cyclooxygenase (COX)-2 protein in the lungs.
      Together, SIN and SIN DE exert significant oral anti-inflammatory effects, which
      rationalize their therapeutic use in the management of sinusitis and other
      viral/microbial nasal infections that are associated with inflammation. Moreover,
      our results suggest that based on the higher efficiency and the accompanied
      reduction of COX-2 expression and PGE(2) formation, the novel dry extract SIN DE
      might be superior over the former SIN drug mixture.

PMID- 22406454
TI  - Three novel beta-carboline alkaloids from Gelsemium elegans.
AB  - Three novel beta-carboline alkaloids characterized with a unique degraded
      monoterpenoid moiety, gelebolines A-C (1-3), together with 11 known alkaloids of
      different types, were isolated from the roots of Gelsemium elegans. The
      structures of new alkaloids were established on the basis of analysis of
      spectroscopic data. It is the first example for report of beta-carboline from
      genus Gelsemium (Loganiaceae).

PMID- 22406455
TI  - Cost of production of live attenuated dengue vaccines: a case study of the
      Instituto Butantan, Sao Paulo, Brazil.
AB  - BACKGROUND: A vaccine to prevent dengue disease is urgently needed. Fortunately,
      a few tetravalent candidate vaccines are in the later stages of development and
      show promise. But, if the cost of these candidates is too high, their beneficial
      potential will not be realized. The price of a vaccine is one of the most
      important factors affecting its ultimate application in developing countries. In
      recent years, new vaccines such as those for human papilloma virus and
      pneumococcal disease (conjugate vaccine) have been introduced with prices in
      developed countries exceeding $50 per dose. These prices are above the level
      affordable by developing countries. In contrast, other vaccines such as those
      against Japanese encephalitis (SA14-14-2 strain vaccine) and meningitis type A
      have prices in developing countries below one dollar per dose, and it is expected
      that their introduction and use will proceed more rapidly. Because dengue disease
      is caused by four related viruses, vaccines must be able to protect against all
      four. Although there are several live attenuated dengue vaccine candidates under
      clinical evaluation, there remains uncertainty about the cost of production of
      these tetravalent vaccines, and this uncertainty is an impediment to rapid
      progress in planning for the introduction and distribution of dengue vaccines
      once they are licensed. METHOD: We have undertaken a detailed economic analysis,
      using standard industrial methodologies and applying generally accepted
      accounting practices, of the cost of production of a live attenuated vaccine,
      originally developed at the US National Institutes of Health (National Institute
      of Allergy and Infectious Diseases), to be produced at the Instituto Butantan in
      Sao Paulo, Brazil. We determined direct costs of materials, direct costs of
      personnel and labor, indirect costs, and depreciation. These were analyzed
      assuming a steady-state production of 60 million doses per year. RESULTS:
      Although this study does not seek to compute the price of the final licensed
      vaccine, the cost of production estimate produced here leads to the conclusion
      that the vaccine can be made available at a price that most ministries of health
      in developing countries could afford. This conclusion provides strong
      encouragement for supporting the development of the vaccine so that, if it proves
      to be safe and effective, licensure can be achieved soon and the burden of dengue
      disease can be reduced.

PMID- 22406456
TI  - Bioencapsulation of the hepatitis B surface antigen and its use as an effective
      oral immunogen.
AB  - Hepatitis B remains a major global health problem despite the availability of a
      safe and effective vaccine. Segments of the population lack access to or respond
      poorly to the parenteral vaccine, perpetuating the infection-transmission cycle.
      A low cost, orally delivered vaccine has the potential to alleviate many of these
      problems. Here we describe the expression of a bioencapsulated hepatitis B
      surface antigen (HBsAg) in maize and its immunogenicity, demonstrating for the
      first time a commercially feasible oral subunit vaccine production system for a
      major disease. This work surmounts previous barriers to plant-produced vaccines
      by expressing HBsAg at much higher levels and retaining antigen immunogenicity
      post-processing: factors which facilitated a robust immune response in mice
      without the need for an adjuvant. This method provides a practical solution to
      the delivery of a low-cost, stable oral vaccine.

PMID- 22406457
TI  - Efficacy of a Gal-lectin subunit vaccine against experimental Entamoeba
      histolytica infection and colitis in baboons (Papio sp.).
AB  - To determine the efficacy of a Gal-lectin based intranasal synthetic peptide
      vaccine, we developed a new experimental primate model of Entamoeba histolytica
      intestinal infection. Release of xenic E. histolytica trophozoites (5*10(6)) into
      the small bowel of baboons (Papio sp.) resulted in a rapid intestinal anti-amebic
      antibody response and a brief infection; however, release of trophozoites
      directly into the cecum (5 baboons) elicited a sustained E. histolytica
      infection, as determined by quantitative fecal PCR, and an ulcerative,
      inflammatory colitis observed on colonoscopy and histopathology. In three
      controlled experiments, baboons received four immunizations at seven day
      intervals of 1600 MUg of the vaccine/nostril, with Cholera toxin, 20 MUg/nostril
      as adjuvant; vaccinated (n=6) and control baboons (n=6) baboons were then
      challenged via colonoscopy with xenic trophozoites (5*10(6)). During 90 days of
      follow up, 250 of 415 (60.24%) fecal samples in control baboons had a (+) PCR for
      E. histolytica, compared to only 36 of 423 (8.51%) samples from vaccinated
      baboons (P<0.001). All 6 vaccinated baboons were free of infection by the 51st
      day after challenge, 5 of 6 controls positive had (+) fecal PCRs for up to 126
      days post-challenge (P=0.019). Inflammatory colitis developed in 4 of 6 control
      baboons post-challenge, with invasive E. histolytica trophozoites present in 2 of
      the 4 on histopathology. There was no evidence of inflammatory colitis or
      parasite invasion in any of the vaccinated baboons; there was a strong inverse
      correlation between positive ELISA OD value indicating the presence of intestinal
      anti-peptide IgA antibodies and baboons having a positive fecal PCR CT value,
      P<0.001. In conclusion, we developed a novel primate model of E. histolytica
      intestinal infection and demonstrated that a Gal-lectin-based intranasal
      synthetic peptide vaccine was highly efficacious in preventing experimental E.
      histolytica infection and colitis in baboons.

PMID- 22406458
TI  - An optimized SIV DNA vaccine can serve as a boost for Ad5 and provide partial
      protection from a high-dose SIVmac251 challenge.
AB  - One limitation in the development of an improved cellular response needed for an
      effective HIV-vaccine is the inability to induce robust effector T-cells capable
      of suppressing a heterologous challenge. To improve cellular immune responses, we
      examined the ability of an optimized DNA vaccine to boost the cellular immune
      responses induced by a highly immunogenic Ad5 prime. Five Chinese rhesus macaques
      received pVax encoding consensus (con) gag/pol/env intramuscularly (IM) with
      electroporation followed by the Merck Ad5 gag/pol/nef vaccine. A second group of
      five animals were vaccinated with Merck Ad5 gag/pol/nef followed by pVax
      gag/pol/env. One year following vaccination, Ad5-prime DNA-boosted monkeys and
      four unvaccinated controls received an intrarectal challenge with 1000 ID50
      SIV(mac)251. The quality and magnitude of the T-cell response was analyzed by
      ELISpot and polyfunctional flow cytometry. We observed that an Ad5-prime DNA
      boost resulted in significantly elevated SIV-specific T-cell responses even
      compared with animals receiving a DNA-prime Ad5-boost. Ad5 prime DNA boosted
      animals were capable of suppressing a pathogenic SIV(mac)251 challenge. Peak
      control correlated with the expansion of HLA-DR(+) CD8(+) T-cells two weeks post
      infection. These data illustrate that high optimization of a DNA vaccine can
      drive of immune responses primed by a robust vector system. This previously
      unachievable feature of these newly optimized DNAs warrants future studies of
      this strategy that may circumvent issues of serology associated with viral vector
      prime-boost systems.

PMID- 22406459
TI  - Vaccination of bovines against Echinococcus granulosus (cystic echinococcosis).
AB  - Hydatid disease is an important human zoonosis. Humans become infected from
      carnivores that are infected with the Echinococcus granulosus tapeworm.
      Carnivores become infected after consuming hydatid cysts from grazing animals,
      which are generally sheep, goats and cattle. A vaccine, known as EG95, can
      protect sheep and goats against cystic echinococcosis. This paper describes the
      adaptation of the EG95 vaccine for use in cattle. The monitoring of results used
      serology and also infection with E. granulosus eggs, followed by necropsy.
      Immunisation with living E. granulosus oncospheres showed that cattle could be
      immunised against E. granulosus. Immunisation of cattle with EG95 plus QuilA was
      also successful. A dose-response and adjuvant trial showed best results were
      achieved with 250 MUg of antigen and 5mg of the adjuvant QuilA, which was 5 times
      the recommended sheep dose. After two vaccinations given one month apart, 90%
      protection was maintained for 12 months. At 12 months a third vaccination boosted
      protection to 99% which was maintained for a further 11 months.

PMID- 22406460
TI  - Influenza A vaccines using linear expression cassettes delivered via
      electroporation afford full protection against challenge in a mouse model.
AB  - Alternative DNA vaccine constructs such as fully synthetic linear expressing
      cassettes (LECs) offer the advantage of accelerated manufacturing techniques as
      well as the lack of both antibiotic resistance genes and bacterial contaminants.
      The speed of manufacture makes LEC technology a possible future vaccination
      strategy for pandemic influenza outbreaks. Previously, we reported on a novel
      concept of DNA delivery to dermal tissue by a minimally invasive electroporation
      (EP) surface device powered using low voltage parameters. This device allows
      electroporation without penetration of electrodes into the skin. In addition to
      enhancing the delivery of traditional plasmid DNA vaccines, this device may also
      offer a safe, tolerable and efficient method to administer LECs. To assess
      immunogenicity and efficacy of EP-enhanced LEC delivery in mice, we designed and
      tested two influenza antigens in the form of LEC constructs delivered using the
      newly developed surface dermal EP device. Strong CTL and antibody responses were
      induced by the LEC versions of the DNA vaccine. When challenged with
      A/Canada/AB/RV1532/2009 viruses, mice immunized with LEC encoding the M2 and NP
      antigens recovered faster than naive or mice immunized ID without EP. Mice
      immunized with equal-molar doses of LEC encoding the M2 and NP antigens
      demonstrated 100% survival following a lethal (100* LD50) challenge of the
      heterologuos and highly pathogenic H5N1 influenza virus (A/Vietnam/1203/04).
      These results suggest that influenza DNA vaccines based on LEC technology
      combined with the surface delivery platform are capable of fully protecting mice
      in a lethal challenge and the LEC based DNA constructs may serve as viable
      vaccine candidates.

PMID- 22406461
TI  - Nutrition in the primary and secondary prevention of stroke.
AB  - Stroke is a worldwide major health issue. As some of the risk factors are
      modifiable, it is of high importance to understand how we can minimize the risk
      for stroke. Multifactorial interventions should be provided to patients in the
      frame of primary and secondary prevention. Obesity is a well-established
      modifiable factor as well as the dietary pattern that mostly depends on the
      social environment, the lifestyle and the habits of each individual. So, dietary
      changes should be part of the holistic approach which includes improvements in
      the regulation of hypertension, hyperlipidaemia and hyperglycaemia. In the
      present review, we try to provide a global approach on how diet can influence the
      risk of stroke and especially the nutritional influence on lipid profile and
      vessel disease and the role of dietary modification in the secondary stroke
      prevention. The importance of salt restriction, DASH and Mediterranean diet low
      in saturated and high in polyunsaturated fats, and the management of obesity seem
      to be the most important dietary priorities.

PMID- 22406462
TI  - Health impact of motorised trips that could be replaced by walking.
AB  - BACKGROUND: We aimed to quantify the number of women and men, in Catalonia, among
      those not achieving physical activity recommendations, making short motorized
      trips which could have been made on foot, and to estimate the annual economic
      benefit due to reducing mortality as a result of replacing one short, daily,
      motorized journey with walking. METHODS: Cross-sectional study. Mobility data
      came from individuals >17 years who reported, in the 2006 Daily Mobility Survey,
      having travelled on the referred working day (N = 80,552). The health economic
      assessment tool for walking (HEAT) from the World Health Organization (WHO)
      Regional Office for Europe was used to calculate the economic benefit. RESULTS:
      Of those not meeting recommendations, 15.6% of men (95% CI 15.2-16.1) and 13.9%
      of women (95% CI 13.5-14.4) would go on to meet them if they were to replace at
      least one short motorized trip per day by walking. If applied to the entire
      population of Catalonia, this change would increase up to 326,557 men (95% CI 313
      373-339,740) and up to 252,509 women (95% CI 240,855-264,163) who would achieve
      recommendations through walking rather than driving. According to HEAT
      estimations, this would suppose a saving of ?124,216,000 (95% CI 120,182,000
      128,250,000) in men and ?84,927,000 (95% CI 81,774,000-88,079,000) in women,
      derived from the reduction in mortality gained from walking accumulated over one
      year. CONCLUSION: This study demonstrates the potential of trips on foot as a
      source of physical activity. It also points out that both benefits for the health
      of the population and a huge economic benefit could have been gained through
      active transportation interventions.

PMID- 22406464
TI  - Association between asleep blood pressure and brain natriuretic peptide during
      antihypertensive treatment:  the Japan Morning Surge-Target Organ Protection (J
      TOP) study.
AB  - BACKGROUND: Asleep blood pressure (BP) has been shown to better reflect
      cardiovascular risk than awake BP in hypertensive patients. This study
      investigated the correlation of brain natriuretic peptide (BNP) to asleep BP
      during antihypertensive treatment. METHODS: In the Japan Morning Surge-Target
      Organ Protection (J-TOP) study, which was an open-label multicenter trial to
      compare bedtime or awakening dosing of candesartan (+ diuretics as needed) among
      individuals with home SBP higher than 135  mmHg, we evaluated 254 hypertensive
      patients who underwent ambulatory BP monitoring, and measured their BNP at
      baseline and after 6th month of treatment. RESULTS: At follow-up, the decrease in
      log-transformed BNP was significantly related to the decrease in asleep SBP (r =
      0.27, P < 0.001); the relationship remained significant (beta = 0.20, P = 0.002)
      even after adjusting for the decrease in the awake SBP (beta = 0.001, P = 0.991).
      When we divided participants by their time of candesartan administration, the
      relationship between the decrease in log-transformed BNP and asleep SBP was still
      significant in both the awakening-dosing group (beta = 0.21, P = 0.028) and the
      bedtime-dosing group (beta = 0.21, P = 0.029). Furthermore, this relationship was
      strong in the participants who were receiving diuretics. CONCLUSION: The decrease
      in BNP is associated with asleep BP reduction by candesartan (+ diuretics as
      needed) over and above the awake BP reduction, regardless of the time of
      administration.

PMID- 22406463
TI  - Position paper on the management of patients with obstructive sleep apnea and
      hypertension: joint recommendations by the European Society of Hypertension, by
      the European Respiratory Society and by the members of European COST (COoperation
      in Scientific and Technological research) ACTION B26 on obstructive sleep apnea.
AB  - This article is aimed at addressing the current state of the art in epidemiology,
      pathophysiology, diagnostic procedures and treatment options for appropriate
      management of obstructive sleep apnea (OSA) in cardiovascular (particularly
      hypertensive) patients, as well as for the management of cardiovascular diseases
      (particularly arterial hypertension) in OSA patients. The present document is the
      result of the work done by a panel of experts participating in the European Union
      COST (COoperation in Scientific and Technological research) ACTION B26 on OSA,
      with the endorsement of the European Respiratory Society (ERS) and the European
      Society of Hypertension (ESH). These recommendations are particularly aimed at
      reminding cardiovascular experts to consider the occurrence of sleep-related
      breathing disorders in patients with high blood pressure. They are at the same
      time aimed at reminding respiration experts to consider the occurrence of
      hypertension in patients with respiratory problems at night.

PMID- 22406465
TI  - Prevalence and associated factors of subclinical hypercortisolism in patients
      with resistant hypertension.
AB  - BACKGROUND: Subclinical hypercortisolism is a secondary cause of hypertension
      that had never been evaluated in resistant hypertensive patients, a subgroup of
      general hypertensive individuals with an expected high prevalence of secondary
      hypertension. METHODS: Four hundred and twenty-three patients with resistant
      hypertension and ages up to 80 years were screened for the presence of
      subclinical hypercortisolism by morning serum cortisol after a midnight 1 mg
      dexamethasone suppression test (DST). Those with morning cortisol of at least 50 
      nmol/l had hypercortisolism confirmed by two salivary cortisol of at least 3.6 
      nmol/l collected at 2300  h. Statistical analysis included bivariate tests
      between those with positive and negative screening test and with and without
      confirmed hypercortisolism, and logistic regressions to assess their independent
      correlates. RESULTS: One hundred and twelve patients (prevalence 26.5%, 95%
      confidence interval 22.0-31.9%) had the screening test positive for suspected
      hypercortisolism. None had overt Cushing syndrome. Patients with positive
      screening were older, more frequently males, had higher prevalences of diabetes
      and target-organ damage and higher nighttime SBPs than patients with normal
      screening test results. Thirty-four patients (total prevalence 8.0%, 95%
      confidence interval: 5.7-11.2%) had confirmed hypercortisolism. Independent
      correlates of a positive DST were older age (P = 0.007), male sex (P = 0.012) and
      presence of cardiovascular diseases (P = 0.002) and chronic kidney disease (P =
      0.016). Correlates of confirmed subclinical hypercortisolism were older age (P =
      0.020), diabetes (P = 0.06) and a nondipping pattern on ambulatory blood pressure
      monitoring (P = 0.04). CONCLUSION: Patients with resistant hypertension had a
      relatively high prevalence of subclinical hypercortisolism, and its presence is
      associated with several markers of worse cardiovascular prognosis.

PMID- 22406466
TI  - Inverted takotsubo cardiomyopathy in a patient with essential thrombocythemia
      exposed to anagrelide and phentermine.

PMID- 22406467
TI  - Models incorporating pin joints are suitable for simulating performance but
      unsuitable for simulating internal loading.
AB  - Simulation models of human movement comprising pin-linked segments have a
      potential weakness for reproducing accurate ground reaction forces during high
      impact activities. While the human body contains many compliant structures such a
      model only has compliance in wobbling masses and in the foot-ground interface. In
      order to determine whether accurate GRFs can be produced by allowing additional
      compliance in the foot-ground interface, a subject-specific angle-driven computer
      simulation model of triple jumping with 13 pin-linked segments was developed,
      with wobbling masses included within the shank, thigh, and trunk segments. The
      foot-ground interface was represented by spring-dampers at three points on each
      foot: the toe, ball, and heel. The parameters of the spring-dampers were varied
      by a genetic algorithm in order to minimise the differences between simulated
      GRFs, and those measured from the three phases of a triple jump in three
      conditions: (a) foot spring compression limited to 20 mm; (b) this compression
      limited to 40 mm; (c) no restrictions. Differences of 47.9%, 15.7%, and 12.4%
      between simulation and recorded forces were obtained for the 20 mm, 40 mm, and
      unrestricted conditions, respectively. In the unrestricted condition maximum
      compressions of between 43 mm and 56 mm were obtained in the three phases and the
      mass centre position was within 4mm of the actual position at these times. It is
      concluded that the unrestricted model is appropriate for simulating performance
      whereas the accurate calculation of internal forces would require a model that
      incorporates compliance elsewhere in the link system.

PMID- 22406468
TI  - Robust estimation of physiological cross-sectional area and geometric
      reconstruction for human skeletal muscle.
AB  - Understanding muscle architecture is crucial to determining the mechanical
      function of muscle during body movements, because architectural parameters
      directly correspond to muscle performance. Accurate parameters are thus essential
      for reliable simulation. Human cadaveric muscle specimen data provides the
      anatomical detail needed for in-depth understanding of muscle and accurate
      parameter estimation. However, as muscle generally has non-uniform architecture,
      parameter estimation, specifically, physiological cross-sectional area (PCSA), is
      rarely straightforward. To deal effectively with this non-uniformity, we propose
      a geometric approach in which a polygon is sought to best approximate the cross
      sectional area of each fascicle by accounting for its three-dimensional
      trajectory and arrangement in the muscle. Those polygons are then aggregated to
      determine PCSA and volume of muscle. Experiments are run using both synthetic
      data and muscle specimen data. From comparison of PCSA using synthetic data, we
      conclude that the proposed method enhances the robustness of PCSA estimation
      against variation in muscle architecture. Furthermore, we suggest reconstruction
      methods to extract 3D muscle geometry directly from fascicle data and estimated
      parameters using the level set method.

PMID- 22406469
TI  - Evidence of changes in load sharing during isometric elbow flexion with ramped
      torque.
AB  - This study aimed to: (1) test the repeatability of Supersonic Shear Imaging
      measures of muscle shear elastic modulus of four elbow flexor muscles during
      isometric elbow flexion with ramped torque; (2) determine the relationship
      between muscle shear elastic modulus and elbow torque for the four elbow flexor
      muscles, and (3) investigate changes in load sharing between synergist elbow
      flexor muscles with increases in elbow flexor torque. Ten subjects performed ten
      isometric elbow flexions consisting of linear torque ramps of 30-s from 0 to 40%
      of maximal voluntary contraction. The shear elastic modulus of each elbow flexor
      muscle (biceps brachii long head [BB(LH)], biceps brachii short head [BB(SH)],
      brachialis [BA], and brachoradialis [BR]) and of triceps brachii long head [TB]
      was measured twice with individual muscles recorded in separate trials in random
      order. A good repeatability of the shape of the changes in shear elastic modulus
      as a function of torque was found for each elbow flexor muscle (r-values: 0.85 to
      0.94). Relationships between the shear elastic modulus and torque were best
      explained by a second order polynomial, except BA where a higher polynomial was
      required. Statistical analysis showed that BB(SH) and BB(LH) had an initial slow
      change at low torques followed by an increasing rate of increase in modulus with
      higher torques. In contrast, the BA shear elastic modulus increased rapidly at
      low forces, but plateaued at higher forces. These results suggest that changes in
      load sharing between synergist elbow flexors could partly explain the non-linear
      EMG-torque relationship classically reported for BB during isometric efforts.

PMID- 22406471
TI  - On the ancestral recruitment of metalloproteinases into the venom of snakes.
AB  - Tracing the evolutionary history of proteins can reveal insights into gene
      alterations responsible for changes in structure and function. Here, the origin
      of snake venom metalloproteinases was rigorously reassessed using phylogenetics
      and the reconstruction of ancestral sequences. Basal SVMPs are most closely
      related to ADAM 7, 28 and decysin-1 proteins. Reconstructing the evolutionary
      history of these proteins and their hypothetical ancestors reveals progressive
      alterations in the amino acid composition and structural characteristics of
      ADAMs/SVMPs through evolutionary time.

PMID- 22406472
TI  - Sponge implant in Swiss mice as a model for studying loxoscelism.
AB  - Envenomation by Loxosceles spider bite leads to a set of signs and symptoms,
      called loxoscelism, which in most cases manifests through the dermonecrotic
      frame. The development of a smaller size animal model, of easy handling and
      maintenance, and lower cost is needed to study the loxoscelism pathogenesis. The
      inflammatory effects of the Loxosceles similis crude venom was evaluated
      considering neutrophil and macrophage activation, vasodilatation, hyperhaemia,
      edema and hemorrhage and TNF-alpha and VEGF production using the murine sponge
      implant model. Thirty two male Swiss mice (6-8 weeks old) were implanted
      subcutaneously with polyether-polyurethane sponge discs. Fourteen days post
      implantation, animals were separated into two groups: (1) control group--16 mice
      received 30 MUL of saline intra-implant; (2) treated group-sixteen mice injected
      with 0.5 MUg/30 MUL of L. similis crude venom intra-implant. The animals were
      euthanized with xylazine/ketamine after 1 and 4 h post- injection.
      Microscopically, implants of the treated groups presented an acute inflammation
      characterized by: neutrophilic infiltrate, edema, vasodilatation hyperhaemia, and
      severe hemorrhage. Some vessels presented ruptured walls. Under morphometric
      analysis, vessel area was bigger in the treated groups compared with the control
      ones. The biochemical parameters, hemoglobin content, inflammatory enzyme
      activities (myeloperoxidase and n-acethyl-beta-D glucosaminidase) and levels of
      the cytokines, TNF-alpha and VEGF, were also significantly higher in the venom
      treated groups. The effects of Loxosceles venom in the granulation tissue of the
      implant in mice were similar to those observed in cutaneous loxoscelism in other
      species (human and rabbits). Consequently, the murine sponge implant model
      provides a new method to investigate cellular/molecular mechanisms associated
      with cutaneous loxoscelism.

PMID- 22406473
TI  - Emotional information in body and background hampers recognition memory for
      faces.
AB  - Emotional influences on memory for events have long been documented yet
      surprisingly little is known about how emotional signals conveyed by contextual
      cues influence memory for face identity. This study investigated how positively
      and negatively valenced contextual emotion cues conveyed by body expressions or
      background scenes influence face memory. The results provide evidence of
      emotional context influence on face recognition memory and show that faces
      encoded in emotional (either fearful or happy) contexts (either the body or
      background scene) are less well recognized than faces encoded in neutral contexts
      and this effect is larger for body context than for scene context. The findings
      are compatible with the hypothesis that emotional signals in visual scenes
      trigger orienting responses which may lead to a less elaborate processing of
      featural details like the identity of a face, in turn resulting in a decreased
      facial recognition memory.

PMID- 22406470
TI  - Orthopoxvirus targets for the development of new antiviral agents.
AB  - Investments in the development of new drugs for orthopoxvirus infections have
      fostered new avenues of research, provided an improved understanding of
      orthopoxvirus biology and yielded new therapies that are currently progressing
      through clinical trials. These broad-based efforts have also resulted in the
      identification of new inhibitors of orthopoxvirus replication that target many
      different stages of viral replication cycle. This review will discuss progress in
      the development of new anti-poxvirus drugs and the identification of new
      molecular targets that can be exploited for the development of new inhibitors.
      The prototype of the orthopoxvirus group is vaccinia virus and its replication
      cycle will be discussed in detail noting specific viral functions and their
      associated gene products that have the potential to serve as new targets for drug
      development. Progress that has been achieved in recent years should yield new
      drugs for the treatment of these infections and might also reveal new approaches
      for antiviral drug development with other viruses.

PMID- 22406474
TI  - Functional networks involved in spatial learning strategies in middle-aged rats.
AB  - Our aim was to assess the way that middle-aged rats solve spatial learning tasks
      that can be performed using different strategies. We assessed the brain networks
      involved in these spatial learning processes using Principal Component Analysis.
      Two tasks were performed in a complex context, a four-arm radial maze, in which
      each group must use either an allocentric or an egocentric strategy. Another task
      was performed in a simple T-maze in which rats must use an egocentric strategy.
      Brain metabolic activity was quantified to evaluate neural changes related to
      spatial learning in the described tasks. Our findings revealed that two
      functional networks are involved in spatial learning in aged rats. One of the
      networks, spatial processing, is composed of brain regions involved in the
      integration of sensory and motivational information. The other network, context
      dependent processing, mainly involves the dorsal hippocampus and is related to
      the processing of contextual information from the environment. Both networks work
      together to solve spatial tasks in a complex spatial environment.

PMID- 22406475
TI  - The Arabidopsis AP2/ERF transcription factor RAP2.11 modulates plant response to
      low-potassium conditions.
AB  - Plants respond to low-nutrient conditions through metabolic and morphology
      changes that increase their ability to survive and grow. The transcription factor
      RAP2.11 was identified as a component in the response to low potassium through
      regulation of the high-affinity K(+) uptake transporter AtHAK5 and other
      components of the low-potassium signal transduction pathway. RAP2.11 was
      identified through the activation tagging of Arabidopsis lines that contained a
      luciferase marker driven by the AtHAK5 promoter that is normally only induced by
      low potassium. This factor bound to a GCC-box of the AtHAK5 promoter in vitro and
      in vivo. Transcript profiling revealed that a large number of genes were up
      regulated in roots by RAP2.11 overexpression. Many regulated genes were
      identified to be in functional categories that are important in low-K(+)
      signaling. These categories included ethylene signaling, reactive oxygen species
      production, and calcium signaling. Promoter regions of the up-regulated genes
      were enriched in the GCCGGC motif also contained in the AtHAK5 promoter. These
      results suggest that RAP2.11 regulates AtHAK5 expression under low-K(+)
      conditions and also contributes to a coordinated response to low-potassium
      conditions through the regulation of other genes in the low-K(+) signaling
      cascade.

PMID- 22406478
TI  - Differentiating patterns of oligoclonal banding in the cerebrospinal fluid
      improves diagnostic utility for multiple sclerosis.
AB  - BACKGROUND: Detection of oligoclonal bands (OCBs) in the cerebrospinal fluid
      (CSF) is an important adjunct to the diagnosis of multiple sclerosis (MS) and
      clinically isolated syndromes (CIS). OCBs are considered present if two or more
      extra IgG bands are present in CSF in comparison to a simultaneously collected
      serum sample. However, using isoelectric focusing and immunofixation with anti
      IgG, we observed two distinct banding patterns, one in which the bands were
      numerous and prominent (which we termed 'delta') and a much more subtle pattern,
      with fewer, more indistinct bands ('theta'). AIM: To perform a prospective study
      to determine the diagnostic implications of the two OCB patterns for multiple
      sclerosis. METHODS: Over a 2-year period, 56 consecutive CSF samples with OCBs
      were identified. Clinical information and radiological data were collected and
      correlated with the two banding patterns. RESULTS: : Of the 56 positive CSF
      samples, 46 (82%) demonstrated a delta pattern, and 10 (18%), a theta pattern.
      The delta pattern was associated with MS/CIS in 34 of 46 (74%) samples, compared
      with zero of the 10 theta samples (0%, p < 0.001). Exclusion of the theta pattern
      samples increased the positive predictive value of OCB testing from 61% to 74%
      for MS/CIS. CONCLUSION: The diagnostic significance of oligoclonal bands in CSF
      for MS/CIS can be improved by restricting interpretation to the delta banding
      pattern alone.

PMID- 22406476
TI  - Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and
      induces autophagy in colorectal cancer cells.
AB  - BACKGROUND & AIMS: Aspirin reduces the incidence of and mortality from colorectal
      cancer (CRC) by unknown mechanisms. Cancer cells have defects in signaling via
      the mechanistic target of rapamycin (mTOR), which regulates proliferation. We
      investigated whether aspirin affects adenosine monophosphate-activated protein
      kinase (AMPK) and mTOR signaling in CRC cells. METHODS: The effects of aspirin on
      mTOR signaling, the ribosomal protein S6, S6 kinase 1 (S6K1), and eukaryotic
      translation initiation factor 4E binding protein 1 (4E-BP1) were examined in CRC
      cells by immunoblotting. Phosphorylation of AMPK was measured; the effects of
      loss of AMPKalpha on the aspirin-induced effects of mTOR were determined using
      small interfering RNA (siRNA) in CRC cells and in AMPK(alpha1/alpha2-/-) mouse
      embryonic fibroblasts. LC3 and ULK1 were used as markers of autophagy. We
      analyzed rectal mucosa samples from patients given 600 mg aspirin, once daily for
      1 week. RESULTS: Aspirin reduced mTOR signaling in CRC cells by inhibiting the
      mTOR effectors S6K1 and 4E-BP1. Aspirin changed nucleotide ratios and activated
      AMPK in CRC cells. mTOR was still inhibited by aspirin in CRC cells after siRNA
      knockdown of AMPKalpha, indicating AMPK-dependent and AMPK-independent mechanisms
      of aspirin-induced inhibition of mTOR. Aspirin induced autophagy, a feature of
      mTOR inhibition. Aspirin and metformin (an activator of AMPK) increased
      inhibition of mTOR and Akt, as well as autophagy in CRC cells. Rectal mucosal
      samples from patients given aspirin had reduced phosphorylation of S6K1 and S6.
      CONCLUSIONS: Aspirin is an inhibitor of mTOR and an activator of AMPK, targeting
      regulators of intracellular energy homeostasis and metabolism. These could
      contribute to its protective effects against development of CRC.

PMID- 22406477
TI  - Zinc fingers and homeoboxes 2 inhibits hepatocellular carcinoma cell
      proliferation and represses expression of Cyclins A and E.
AB  - BACKGROUND & AIMS: Zinc-fingers and homeoboxes 2 (ZHX2) represses transcription
      of several genes associated with liver cancer. However, little is known about the
      role of ZHX2 in the development of hepatocellular carcinoma (HCC). We
      investigated the mechanisms by which ZHX2 might affect proliferation of HCC
      cells. METHODS: We overexpressed and knocked down ZHX2 in HCC cells and analyzed
      the effects on proliferation, colony formation, and the cell cycle. We also
      analyzed the effects of ZHX2 overexpression in growth of HepG2.2.15 tumor
      xenografts in nude mice. Chromatin immunoprecipitation and luciferase reporter
      assays were used to measure binding of ZHX2 target promoters. Levels of ZHX2 in
      HCC samples were evaluated by immunohistochemistry. RESULTS: ZHX2 overexpression
      significantly reduced proliferation of HCC cells and growth of tumor xenografts
      in mice; it led to G1 arrest and reduced levels of Cyclins A and E in HCC cell
      lines. ZHX2 bound to promoter regions of CCNA2 (which encodes Cyclin A) and CCNE1
      (which encodes Cyclin E) and inhibited their transcription. Knockdown of Cyclin A
      or Cyclin E reduced the increased proliferation mediated by ZHX2 knockdown.
      Nuclear localization of ZHX2 was required for it to inhibit proliferation of HCC
      cells in culture and in mice. Nuclear localization of ZHX2 was reduced in human
      HCC samples, even in small tumors (diameter, <5 cm), compared with adjacent
      nontumor tissues. Moreover, reduced nuclear levels of ZHX2 correlated with
      reduced survival times of patients, high levels of tumor microvascularization,
      and hepatocyte proliferation. CONCLUSIONS: ZHX2 inhibits HCC cell proliferation
      by preventing expression of Cyclins A and E, and reduces growth of xenograft
      tumors in mice. Loss of nuclear ZHX2 might be an early step in the development of
      HCC.

PMID- 22406479
TI  - An in depth analysis of histopathological characteristics found in keratoconus.
AB  - AIMS: The aims of this study were to re-assess the histopathology of the disease
      by introducing more modern measuring techniques and to determine if axial stromal
      thinning, which is the most apparent change, is related to the other alterations
      observed. METHODS: Recipient keratoconic corneas from 36 patients following
      corneal transplantation were studied. Haematoxylin and eosin (H&E) and periodic
      acid-Schiff (PAS) staining were used to identify breaks in Bowman's layer and
      Descemet's membrane. Thickness of corneal layers was measured by Leica QWin
      software. Epithelial and stromal thickness were measured in each sample at the
      periphery of the corneal button and at the area of maximal stromal thinning. The
      presence of apoptotic cells in Bowman's layer breaks was detected by terminal
      deoxynucleotidyl transferase mediated dUTP-X nick end labelling. RESULTS: In all
      36 corneal samples the central stroma, at the apex of the cone, was thinner than
      the peripheral. There was a negative correlation between central stromal and
      central epithelial thickness (p = 0.009). Bowman's layer breaks were found in 92%
      of corneas. Apoptotic cells were detected at the level of Bowman's breaks
      membrane. We found a positive correlation between epithelial thickness and the
      number of Bowman's layer breaks (p = 0.009 for central epithelial thickness and p
      = 0.003 for peripheral epithelial thickness). Descemet's membrane deformities
      were observed in 19% of corneas and central stromal thickness of these corneas
      was significantly less than corneas without breaks (p = 0.006). CONCLUSIONS:
      There are various different histopathological features associated with
      keratoconus and some of them are very subtle and not very well studied. Accurate
      measurements also suggest some correlations between them. Stromal thinning is
      associated with the number of breaks in Descemet's membrane, but it is the
      thickening of the epithelium which is associated with breaks in Bowman's layer.

PMID- 22406480
TI  - Serpin B4 isoform overexpression is associated with aberrant epithelial
      proliferation and lung cancer in idiopathic pulmonary fibrosis.
AB  - AIMS: The aim of the study was to evaluate the role of Serpin B3/B4 in advanced
      idiopathic pulmonary fibrosis (IPF) patients, mainly focusing on epithelial
      proliferation. METHODS: Lungs from 48 IPF patients (including cases with cancer
      or high-grade epithelial dysplasia) were studied and compared with other diffuse
      parenchymal diseases and normal lungs. Immunohistochemistry for Serpin B3/B4 and
      Ki-67 was quantified in all cases, distinguishing stained metaplastic cells. In
      IPF patients correlations between Serpin expression and several
      clinicopathological data, including fibrotic remodelling [fibrosis extension and
      transforming growth factor beta expression (TGF-beta)] were performed. Molecular
      analysis was used for Serpin isoform characterisation. RESULTS: In IPF patients
      Serpin B3/B4 and Ki-67 were significantly overexpressed in many metaplastic cells
      (mainly squamous type) compared to control cases. Higher Serpin B3/B4 was found
      in older patients and cases with more impaired respiratory function. Serpin B3/B4
      expression was related to both TGF-beta and Ki-67 and was higher in patients with
      cancer/high-grade dysplasia. Serpin B3 was expressed in all cases, whereas Serpin
      B4 was expressed only in IPF. CONCLUSIONS: Serpin B3/B4, particularly Serpin B4,
      appears to play an important role in aberrant epithelial proliferation.
      Evaluation of Serpin B3/B4 could have prognostic value in predicting disease
      progression, especially in patients with increased susceptibility to lung cancer.

PMID- 22406481
TI  - Utility of p63 and high molecular weight cytokeratin in the distinction between
      urothelial carcinoma with prostatic stromal invasion and urothelial carcinoma
      with colonisation of prostatic ducts and acini.
AB  - AIMS: To evaluate the utility of p63 and high molecular weight cytokeratin in the
      distinction between urothelial carcinoma with prostatic stromal invasion and
      urothelial carcinoma with colonisation of prostatic ducts and acini which may be
      challenging on H&E, especially for general pathologists who may occasionally
      encounter these cases. METHODS: A search of surgical pathology and consultation
      files was made for cystoprostatectomy specimens with confirmed urothelial
      carcinoma with prostatic stromal invasion. Intensity for both p63 and high
      molecular weight cytokeratin within the tumour cells were scored as negative/weak
      or strong. RESULTS: A total of 34 cases were identified, 23 (68%) of which had
      associated foci of urothelial carcinoma with colonisation of prostatic ducts and
      acini. Mean patient age was 68.5 years (range 44-88 years). In all cases, basal
      cells of benign prostatic glands showed strong staining for both p63 and high
      molecular weight cytokeratin. Seventeen of 34 cases (50%) of urothelial carcinoma
      showed no or weak expression of high molecular weight cytokeratin in the tumour
      cells. The other 17 cases (50%) of urothelial carcinoma showed strong expression
      of high molecular weight cytokeratin in the tumour cells. Fourteen of 34 cases
      (41%) showed negative or weak expression of p63 in tumour cells. Twenty of 34
      cases (59%) showed strong expression of p63 in tumour cells. In the 14 of 34
      cases (41%) and 17 of 34 cases (50%) which showed negative/weak expression of p63
      and high molecular weight cytokeratin, respectively, in the tumour cells, the
      positive staining of the basal cells by p63 and high molecular weight cytokeratin
      in the benign prostatic glands and acini or those colonised by urothelial
      carcinoma, aided in the distinction from urothelial carcinoma with prostatic
      stromal invasion. In the remaining 20 of 34 cases (59%) and 17 of 34 cases (50%)
      in which the tumour cells showed strong expression of p63 and high molecular
      weight cytokeratin, respectively, larger malignant tumour cells and smaller
      benign basal cells of the prostatic glands and acini were highlighted with these
      markers, and were easily distinguishable. CONCLUSION: Our study suggests that p63
      and high molecular weight cytokeratin may be utilised in the distinction between
      urothelial carcinoma with prostatic stromal invasion and urothelial carcinoma
      with colonisation of prostatic ducts and acini.

PMID- 22406482
TI  - Microscopic assessment of fresh prostate tumour specimens yields significantly
      increased rates of correctly annotated samples for downstream analysis.
AB  - AIMS: To assess if performing frozen sections of tissue biopsies from fresh
      radical prostatectomy specimens, prior to tissue banking, could improve the
      identification of the banked samples compared to standard fresh tumour banking
      procedures. METHODS: Tissue biopsies banked from 332 fresh prostatectomy
      specimens were assessed for accuracy of diagnosis, comparing two separate methods
      of tumour identification: one in which tumour was identified in the gross
      specimen by visual inspection (n = 155) and one in which rapid frozen sectioning
      was applied (n = 177). The associations with correct tumour annotation and
      clinicopathological variables, including age, pre-operative prostate specific
      antigen (PSA) levels, pathological Gleason score, pathological T stage, tumour
      volume and surgical margins, were examined using univariable and multivariable
      binary logistic regression models. RESULTS: For the gross visual inspection
      cohort the rate of correctly identifying and banking specimens containing
      prostate cancer was 69%. For the cohort assessed with rapid frozen sections, 94%
      of banked specimens actually had cancer. On multivariable analysis, we found that
      only frozen sectioning and tumour volume variables were independent predictors of
      correctly banked tumour specimens whilst all other routinely reported
      pathological variables had no influence on the success rates of fresh prostate
      tumour banking. CONCLUSION: The success rate for correctly banking fresh prostate
      tumour specimens is directly related to the tumour volume. Frozen section
      scrutiny of prostate samples is recommended to prevent misclassification of the
      banked material.

PMID- 22406483
TI  - Telomerase expression as a predictive marker of radiotherapy response in rectal
      cancer.
AB  - AIMS: To investigate telomerase as a predictive marker of radiotherapy response
      in rectal cancer. METHODS: Expression of the telomerase catalytic subunit hTERT
      was quantified with reverse transcription PCR in the radioresistant colorectal
      cancer cell line SW620 following exposure to 5Gy of radiation. Additionally, 52
      rectal cancer cases were pre-operatively treated with either the short (n = 19)
      or long (n = 33) course radiotherapy (SCR, LCR, respectively) regimes, before and
      after which their hTERT expressions were semi-quantified with
      immunohistochemistry (IHC). This was correlated with the histological tumour
      regression in the resected bowel, dichotomised into good and poor responses.
      RESULTS: SW620 cells expressed gradually increasing levels of hTERT after
      radiation. hTERT IHC positivity of <=75% tumour cells in pre-radiotherapied
      cancer was the optimal negative cut-off level [sensitivity 63.2%, specificity
      45.8%, area under curve (AUC) 0.5362] in predicting good tumour response. As
      significantly more LCR cases showed good tumour response (p<0.0001), the SCR
      cases were excluded and AUC re-analysed, which still remained low (0.5357).
      CONCLUSIONS: While our in vitro results suggest that hTERT up-regulation may
      contribute to radiation resistance of colorectal cancer cells, our in vivo
      results demonstrated poor ability of hTERT IHC in predicting histological tumour
      regression in rectal cancer.

PMID- 22406484
TI  - Molecular pathways involved in crosstalk between cancer cells, osteoblasts and
      osteoclasts in the invasion of bone by oral squamous cell carcinoma.
AB  - AIMS: This study investigates whether matrix metalloproteinases (MMPs),
      specifically MMP-2 and MMP-9, interacting with other molecules important in
      osteoblast differentiation and osteoclastogenesis, could play important roles in
      the invasion of bone by oral squamous cell carcinoma (OSCC). METHODS: Supernatant
      (conditioned medium, CM) was collected from OSCC cell lines (SCC15 and SCC25),
      and from cultured osteoblasts (hFOB cell line and a primary culture, OB), and
      used for indirect co-culture: OSCC cells were treated with CM from osteoblasts
      and vice versa. Zymogenic activities of MMP-2 and -9, and protein quantities of
      all molecules studied, were detected by gelatine zymography and Western blotting,
      respectively. Real-time polymerase chain reaction (PCR) analysed mRNA of these
      molecules. Targeted molecules were examined by immunohistochemistry in tissue
      sections of bone-invasive OSCCs. RESULTS: Zymogenic activities of both MMPs were
      increased in OSCC cells following culture with CM from hFOB: Twist1 protein
      expression was increased while Runx2 did not alter. The RANKL/OPG ratio, zymogen
      and protein expression of MMP-9 were increased in hFOB cells cultured with CM
      from OSCC lines, while zymogen expression of MMP-2 was decreased. Real-time PCR
      showed generally similar changes in expression of these molecules. All targeted
      molecules were expressed in invading malignant keratinocytes, and all but OPG
      were expressed in osteoclasts of clinical samples. CONCLUSIONS: Crosstalk between
      different cell types appears to exist in the invasion of bone by OSCC.
      Understanding and ultimately interfering with the molecules involved may provide
      therapeutic approaches to inhibit such bone invasion.

PMID- 22406485
TI  - Cardiomegaly is a common arrhythmogenic substrate in adult sudden cardiac deaths,
      and is associated with obesity.
AB  - BACKGROUND: Both coronary artery disease (CAD) and cardiomyopathy may present
      with sudden cardiac death (SCD). It is generally accepted that CAD is the most
      common cause of SCD in adults, but the frequency of cardiomegaly as a primary or
      contributing cause is less known. METHODS: We retrospectively studied the cardiac
      findings of all cases of adult SCD attributed to cardiomegaly, severe
      atherosclerosis, or both, in the absence of specific cardiomyopathy. Association
      between findings and risk factors was studied. RESULTS: There were 484 sudden
      cardiac deaths, of which 402 met study criteria. Mean age was 49 +/- 13 years,
      with 289 men and 159 African Americans (AAs). Cardiomegaly with presumed
      hypertensive, multifactorial or unknown cause, was the sole arrhythmogenic
      substrate in 38% of men and 49% of women (p = 0.003); CAD was the sole cause of
      SCD in 19% of men and 26% of women, and mixed CAD + cardiomegaly the cause of
      death in 43% of men and 25% of women. Cardiomegaly was associated by univariate
      analysis with younger age (46 +/- 12 years versus 53 +/- 14 for CAD, p < 0.0001),
      AA race (p = 0.004), and body mass index (p < 0.0001). CONCLUSIONS: Among adults
      with a mean age of about 50 years, cardiomegaly is a frequent cause of sudden
      cardiac death, and is highly associated with obesity. Cardiomegaly is also
      frequent in SCD with severe CAD. The causes and classification of cardiomegaly in
      patients without specific cardiomyopathy, and in patients with and without
      hypertension or coronary disease need to be better studied.

PMID- 22406486
TI  - Variation in BCL2 protein expression in follicular lymphomas without t(14;18)
      chromosomal translocations.
AB  - AIM: The hallmark of follicular lymphoma is the t(14;18)(q32;q21) chromosomal
      translocations that lead to deregulation of BCL2 expression in tumour cells.
      However, not all cases of follicular lymphoma express BCL2, nor is the t(14;18)
      translocation always present. Follicular lymphomas lacking the BCL2 rearrangement
      are less well studied with regards to their immunohistochemical and molecular
      features. This study aims to investigate the BCL2 protein expression pattern in
      t(14;18) negative follicular lymphomas. METHODS: BCL2 protein expression pattern
      was analysed in 26 cases of t(14;18) negative follicular lymphoma [determined by
      fluorescence in situ hybridisation (FISH)], using antibodies against two
      different epitopes, i.e., the widely-used antibody BCL2/124 and an alternative
      antibody E17. RESULTS: Two of the t(14;18) negative cases showed evidence of BCL2
      amplification and trisomy 18. A total of 13 cases (50%) lacked BCL2 expression.
      In 10 cases (38%) the expression was heterogeneous and in only three cases (12%)
      the BCL2 expression was strongly positive. These cases could thus be subdivided
      into three subgroups: Group I, normal BCL2 genes (i.e., no evidence of
      translocation or amplification), and BCL2 protein negative; Group II, normal BCL2
      genes but BCL2 protein positive; and Group III, presence of other genetic
      alterations, i.e., BCL2 amplification and trisomy 18, and BCL2 protein positive.
      CONCLUSIONS: This study suggests that it may be possible on the basis of staining
      to predict that the t(14;18) translocation is absent if a case is either negative
      for BCL2 protein with different antibodies or has heterogeneous BCL2 expression,
      possibly acquired through a physiological process of differentiation.

PMID- 22406487
TI  - The liver sieve and atherosclerosis.
AB  - SUMMARY: The 'liver sieve' is a term developed to describe the appearance and the
      role of fenestrations in the liver sinusoidal endothelial cell (LSEC). LSECs are
      gossamer-thin cells that line the hepatic sinusoid and they are perforated with
      pores called fenestrations clustered in sieve plates. There is growing evidence
      that fenestrations act like a permselective ultrafiltration system which is
      important for the hepatic uptake of many substrates, particularly chylomicron
      remnant lipoproteins. The liver sieve is a very efficient exchange system,
      however in conditions such as hepatic cirrhosis and fibrosis, diabetes mellitus
      and old age, there is defenestration of the liver sieve. Such defenestration has
      been shown to influence the hepatic uptake of various substrates including
      lipoproteins. In the future, pharmacological manipulation of the liver sieve may
      play a number of therapeutic roles including the management of dyslipidaemia;
      increasing the efficiency of liver-targeted gene therapy; and improving
      regeneration of old livers.

PMID- 22406488
TI  - Prolonged motor skill learning--a combined behavioural training and theta burst
      TMS study.
AB  - PURPOSE: To assess the behavioural effects of prolonged motor practice in healthy
      volunteers, and the specific impact of inhibiting different motor-related brain
      regions in the late phase of motor learning using continuous theta burst
      transcranial magnetic stimulation (cTBS). METHODS: Twelve subjects trained their
      non-dominant arm in eight arm motor tasks (Arm Ability Training, AAT) once a day
      for three weeks (16 sessions). During the last four days, training was performed
      before and after applying cTBS to either M1, S1, SMA, or PMC. RESULTS: The AAT
      induced substantial and robust motor learning for the trained arm with variations
      across tasks. Considerable motor learning was also observed in the non-trained
      dominant arm with remarkably similar variations across tasks, suggesting that
      practise improved common underlying sensorimotor capacities (abilities) in
      addition to effector-specific effects. When applied after prolonged training,
      inhibitory cTBS showed no detrimental effects on motor performance/learning; M1
      cTBS even improved performance in a labyrinth task. CONCLUSIONS: Prolonged
      training with the non-dominant arm led to profound motor learning across
      abilities with transfer to the non-trained dominant arm. Unlike during early
      stages of motor learning, no detrimental effect of cTBS over M1, S1, PMC, or SMA
      could be substantiated after prolonged motor practice.

PMID- 22406489
TI  - Quantitative analysis of cellular senescence phenotypes using an imaging
      cytometer.
AB  - Until now, various stimuli as well as serial passaging have been known to induce
      cellular senescence in normal human diploid fibroblasts. However, in many cases,
      we have encountered difficulty in quantitatively analyzing the cellular
      senescence phenotypes of senescent cells in a physiological condition. High
      content screening (HCS)-based image analysis is becoming an important and
      powerful research tool. In the present study, an automated and quantitative
      cellular image-analysis system was employed to quantify the cellular senescence
      phenotypes induced in normal human diploid fibroblasts, TIG-1 cells, and found to
      be a powerful tool in the cellular senescence study.

PMID- 22406490
TI  - Studying the effect of crowding and dehydration on DNA G-quadruplexes.
AB  - Intracellular environment is crowded with biomolecules that occupy a significant
      fraction (up to 40%) of the cellular volume, with a total concentration in the
      range 300-400mg/ml. Recently, the effect of crowding/dehydrating agents on the
      DNA G-quadruplexes has become a subject of an increasing interest. Crowding
      and/or dehydrating agents have been used to simulate how G-quadruplexes behave
      under cell-mimicking conditions characterized by a large excluded volume and a
      lower water activity. Indeed, the presence of both steric crowding and a lower
      water activity can affect G-quadruplex stability, their folding/unfolding
      kinetics, as well as their binding processes with proteins or small ligands. Many
      of these effects can be explored experimentally by measuring the dependence of
      the conformational stability, isomerisation kinetics and equilibria on the
      concentration of cosolutes which do not interact with the molecules (G
      quadruplexes) under investigation. Spectroscopic methodologies, like circular
      dichroism, UV and fluorescence, have been widely employed to study G-quadruplexes
      in dilute solution. Here we focus on some aspects that need to be taken into
      account when employing such techniques in the presence of large amount of a
      cosolute. Additionally, we discuss possible problems/artifacts that arise in
      setting experiments in presence of these commonly employed cosolutes and in
      interpreting the results.

PMID- 22406491
TI  - Serodiagnosis of Lyme borreliosis with bead based immunoassays using multiplex
      technology.
AB  - The serological diagnosis of Lyme borreliosis is accomplished by the detection of
      IgG and IgM antibodies specific for relevant antigens of the spirochetal pathogen
      Borrelia burgdorferi. Instead of the usual enzyme immune assay for screening and
      the Western blot technique for confirmation, bead based multiplex assays with
      multiple simultaneously performed distinct reactions can provide quick,
      automatically derived and reliable results in a single run by flow cytometer
      technology. The broad analytical dynamic range of assay signals and the high
      sensitivity and specificity of the multiplex formats allow even for a reliable
      use in CSF based analyses for antibody specificity index in supposed
      neuroborreliosis. Fluorescence intensity of the bead based reactions can be
      transformed into quantified values as U/ml, either for each single antigen or
      summed up for a group of relevant key antigens. Additionally or alternatively
      distinct reactions of single bead populations can be transformed to Western blot
      band equivalents. Internal and external quality controls with the multiplex
      systems show characteristic data equivalent to the conventional assay formats, so
      that the advantages of the multiplex assays are ready for use in the routine
      diagnostic laboratory.

PMID- 22406492
TI  - A streptavidin paramagnetic-particle based competition assay for the evaluation
      of the optical selectivity of quadruplex nucleic acid fluorescent probes.
AB  - Although quadruplex nucleic acids are thought to be involved in many biological
      processes, they are massively overwhelmed by duplex DNA in the cell. Small
      molecules, able to probe quadruplex nucleic acids with high optical selectivity,
      could possibly achieve the visualization of these processes. The aim of the
      method described herein is to evaluate quickly the optical selectivity of
      quadruplex nucleic acid probes, in isothermal conditions, using widely available
      materials, small quantities of oligonucleotides and virtually any kind and
      quantity of biological competitor. The assay relies on the use of streptavidin
      coated paramagnetic particles and biotinylated quadruplex forming
      oligonucleotides, allowing a quick and easy separation of the quadruplex target
      from the competitor. In the present study, two quadruplex nucleic acids (the DNA
      and RNA human telomeric repeats) have been used as targets while a duplex DNA
      oligonucleotide, total DNA, total RNA, another quadruplex nucleic acid and a
      protein have been used as competitors. The optical selectivity of various probes,
      displaying different photophysical properties and binding selectivities, has been
      successfully examined, allowing the identification of a best candidate for
      further cell microscopy experiments. This assay allows a quick and reliable
      assessment of the labeling properties of a quadruplex binder in cellular
      environment conditions. It is an interesting alternative to gel electrophoresis
      experiments since it is performed in solution, has a well-resolved separation
      system and allows easy quantifications.

PMID- 22406493
TI  - Biofilm formation on nanostructured titanium oxide surfaces and a
      micro/nanofabrication-based preventive strategy using colloidal lithography.
AB  - The contamination of implant devices as a result of biofilm formation through
      bacterial infection has instigated major research in this area, particularly to
      understand the mechanism of bacterial cell/implant surface interactions and their
      preventions. In this paper, we demonstrate a controlled method of nanostructured
      titanium oxide surface synthesis using supersonic cluster beam depositions. The
      nanoscale surface characterization using atomic force microscopy and a
      profilometer display a regulated evolution in nanomorphology and physical
      properties. X-ray photoelectron spectroscopy analyses display a stoichiometric
      nanostructured TiO(2) film.  Measurement of the water contact angle shows a
      nominal increase in the hydrophilic nature of ns-TiO(2) films, whereas the
      surface energy increases with decreasing contact angle. Bacterial species
      Staphylococcus aureus and Escherichia coli interaction with nanostructured
      surfaces shows an increase in adhesion and biofilm formation with increasing
      nanoscale morphological properties. Conversely, limiting ns-TiO(2) film
      distribution to micro/nanopatterned designed substrates integrated with bovine
      serum albumin functionalization leads to a reduction in biofilm formations due to
      a globally decreased bacterial cell-surface interaction area. The results have
      potential implications in inhibiting bacterial colonization and promoting
      mammalian cell-implant interactions.

PMID- 22406494
TI  - A clinical study of alveolar bone tissue engineering with cultured autogenous
      periosteal cells: coordinated activation of bone formation and resorption.
AB  - In ongoing clinical research into the use of cultured autogenous periosteal cells
      (CAPCs) in alveolar bone regeneration, CAPCs were grafted into 33 sites (15 for
      alveolar ridge augmentation and 18 for maxillary sinus lift) in 25 cases. CAPCs
      were cultured for 6weeks, mixed with particulate autogenous bone and platelet
      rich plasma, and then grafted into the sites. Clinical outcomes were determined
      from high-resolution three-dimensional computed tomography (3D-CT) images and
      histological findings. No serious adverse events were attributable to the use of
      grafted CAPCs. Bone regeneration was satisfactory even in cases of advanced
      atrophy of the alveolar process. Bone biopsy after bone grafting with CAPCs
      revealed prominent recruitment of osteoblasts and osteoclasts accompanied by
      angiogenesis around the regenerated bone. 3D-CT imaging suggested that remodeling
      of the grafted autogenous cortical bone particles was faster in bone grafting
      with CAPCs than in conventional bone grafting. The use of CAPCs offers cell-based
      bone regeneration therapy, affording complex bone regeneration across a wide
      area, and thus expanding the indications for dental implants. Also, it enables
      the content of particulate autogenous bone in the graft material to be reduced to
      as low as 40%, making the procedure less invasive, or enabling larger amounts of
      graft materials to be prepared. It may also be possible to dispense with the use
      of autogenous bone altogether in the future. The results suggest that CAPC
      grafting induces bone remodeling, thereby enhancing osseointegration and
      consequently reducing postoperative waiting time after dental implant placement.

PMID- 22406495
TI  - Is the association between various emotion-regulation skills and mental health
      mediated by the ability to modify emotions? Results from two cross-sectional
      studies.
AB  - BACKGROUND AND OBJECTIVES: In order to clarify mechanisms underlying the
      association between emotion regulation and psychopathology, we tested whether the
      ability to modify negative emotions mediates the associations of other emotion
      regulation skills with psychopathological symptoms in two studies. METHODS: The
      first study included 151 college students; the second included 121 psychiatric
      inpatients. Bootstrapping-enhanced mediation analyses were utilized to assess
      associations between self-reports of emotion-regulation skills and
      psychopathology, as well as potential mediation effects. RESULTS: In both
      samples, the ability to modify emotions completely mediated the association
      between symptoms and skills for most skills, but not for the skill of
      accepting/tolerating negative emotions. LIMITATIONS: Major limitations include
      the use of a cross-sectional design as well as exclusive use of self-report data.
      CONCLUSIONS: The ability to modify negative emotions may be the common pathway by
      which many emotion-regulation skills exert their influence on mental health;
      however, the skill of accepting/tolerating negative emotions may be beneficial to
      mental health regardless of whether or not it facilitates modification of
      emotions.

PMID- 22406496
TI  - Genome-wide identification of Dicer-like, Argonaute and RNA-dependent RNA
      polymerase gene families and their expression analyses in response to viral
      infection and abiotic stresses in Solanum lycopersicum.
AB  - Dicer, Argonaute and RNA-dependent RNA polymerase form the core components to
      trigger RNA silencing. Although tomato (Solanum lycopersicum) is a dicotyledon
      model plant, no systematic analysis and expression profiling of these genes in
      tomato has been undertaken previously. In this study, seven Dicer-like (SlDCLs),
      15 Argonaute (SlAGOs) and six RNA-dependent RNA polymerase (SlRDRs) genes were
      identified in tomato. These genes were categorized into four subgroups based on
      phylogenetic analyses. Comprehensive analyses of gene structure, genomic
      localization and similarity among these genes were performed. Their expression
      patterns were investigated by means of expression models in different tissues and
      organs using online data and semi-quantitative RT-PCR. Many of the candidate
      genes were up-regulated in response to Tomato yellow leaf curl virus infection
      and abiotic stresses. The expression models of tandem gene duplications among
      SlDCL2s indicated the DCL2 family plays an important role in the evolution of
      tomato.

PMID- 22406497
TI  - Applying DNA barcodes for identification of plant species in the family
      Araliaceae.
AB  - An effective DNA marker in authentication of the family Araliaceae was screened
      out of the five DNA regions (matK, rbcL, ITS2, psbA-trnH and ycf5). In the
      present study, 1113 sequences of 276 species from 23 genera (Araliaceae) were
      collected from DNA sequencing and GenBank, in which 16 specimens were from 5
      provinces in China and Japan. All of the sequences were assessed in the success
      rates of PCR amplifications, intra- and inter-specific divergence, DNA barcoding
      gaps and efficiency of identification. Compared with other markers, ITS2 showed
      superiority in species discrimination with an accurate identification of 85.23%
      and 97.29% at the species and genus levels, respectively, in plant samples from
      the 589 sequences derived from Araliaceae. Consequently, as one of the most
      popular phylogenetic markers, our study indicated that ITS2 was a powerful
      barcode for Araliaceae identification.

PMID- 22406498
TI  - Ellis-van Creveld syndrome in a fetus with rhizomelia and polydactyly. Report of
      a case diagnosed by genetic analysis, and correlation with pathological
      andradiologic findings.
AB  - Ellis-van Creveld syndrome is an autosomal recessive disorder mainly
      characterized by a disproportionate limb dwarfism, chondroectodermal dysplasia,
      congenital heart disease, postaxial polydactyly, and dysplastic fingernails and
      teeth. Only 300 cases have been published worldwide. We report a 21-week fetus
      with rhizomelia and polydactyly detected. Gross photographs, radiologic studies
      and pathological study were performed leading to the clinico-pathological
      suspicion of EvC. DNA from fresh fetal tissue was extracted for sequencing the
      EVC and EVC2 genes. p.W215X and p.R677X mutations were identified in the EVC2
      gene in the fetal sample. Parental sample analysis showed the p.W215X mutation to
      be inherited from the mother and the p.R677X mutation from the father. The
      clinical information is essential not only to arrive at a correct diagnosis in
      fetuses with pathologic ultrasound findings, but also to offer a proper genetic
      counseling to the parents and their relatives.

PMID- 22406499
TI  - Eight-alanine duplication in homeobox D13 in a Chinese family with
      synpolydactyly.
AB  - Human synpolydactyly (SPD), belonging to syndactyly (SD) II, is an inherited
      autosomal-dominant limb malformation characterized by SD of finger 3 or 4 or toe
      4 or 5, usually with digit duplication. Previous studies have demonstrated that
      homeobox protein D13 (HOXD13) is responsible for this Mendelian disorder. In this
      paper, we report on a family with SPD - 7 members show typical SPD malformations.
      We used PCR and Sanger sequencing of DNA from peripheral blood samples and found
      an 8-Ala expansion in exon 1 of HOXD13 by mutation detection; this variant was
      absent in unaffected members and in 50 unaffected non-related subjects. This
      study further confirmed the correlation between SPD and alanine expansion in
      HOXD13.

PMID- 22406500
TI  - Understanding the neural mechanisms involved in sensory control of voice
      production.
AB  - Auditory feedback is important for the control of voice fundamental frequency
      (F0). In the present study we used neuroimaging to identify regions of the brain
      responsible for sensory control of the voice. We used a pitch-shift paradigm
      where subjects respond to an alteration, or shift, of voice pitch auditory
      feedback with a reflexive change in F0. To determine the neural substrates
      involved in these audio-vocal responses, subjects underwent fMRI scanning while
      vocalizing with or without pitch-shifted feedback. The comparison of shifted and
      unshifted vocalization revealed activation bilaterally in the superior temporal
      gyrus (STG) in response to the pitch shifted feedback. We hypothesize that the
      STG activity is related to error detection by auditory error cells located in the
      superior temporal cortex and efference copy mechanisms whereby this region is
      responsible for the coding of a mismatch between actual and predicted voice F0.

PMID- 22406501
TI  - Impact of hemodynamic effects on diffusion-weighted fMRI signals.
AB  - In some recent studies, diffusion weighted functional MRI has been proposed to
      provide contrast immune to vascular changes. Increases in relative signal change
      during neuronal activation observed under increasing diffusion weighting support
      the possible diffusion based origin of this contrast. A recent diffusion tensor
      imaging (DTI) study has also reported the use of Fractional Anisotropy (FA) to
      track activation in white matter. In this study we aimed to establish if
      relatively high diffusion weighting (b=1200 and 1800 s/mm(2)) eliminates the
      strong vascular influences brought about by 100% O(2) and carbogen (95%O(2)+5%
      CO(2)) induced vascular challenges in gray matter (GM) and white matter (WM) of
      rat brain. We also aimed to characterize the influences of these vascular changes
      on FA, both in GM and in WM. Our study endorses previous reports that even
      relatively heavily diffusion weighted data can be significantly influenced by
      hemodynamic changes. However, this was not only observed in GM, but also in WM.
      Moreover, our study demonstrates that the estimator used to calculate the
      relative changes should be carefully chosen in order to avoid biases at low
      signal-to-noise ratios (SNRs) which accompany increasing diffusion weighting.
      With the use of robust estimators, we found no increases in relative change with
      increasing b-value during both vascular challenges. Our data also demonstrate
      that FA can be significantly influenced by hemodynamics, both in GM and in WM.
      The observed influence of diffusion weighting direction on relative signal change
      in GM was shown to be associated with structural differences among various
      regions. If diffusion based functional contrasts immune to hemodynamics do exist,
      our results highlight the difficulty in discerning those diffusion changes from
      accompanying vascular changes.

PMID- 22406502
TI  - Activation amplitude and temporal synchrony among back extensor and abdominal
      muscles during a controlled transfer task: comparison of men and women.
AB  - Muscle synergies are important for spinal stability, but few studies examine
      temporal responses of spinal muscles to dynamic perturbations. This study
      examined activation amplitudes and temporal synergies among compartments of the
      back extensor and among abdominal wall muscles in response to dynamic
      bidirectional moments of force. We further examined whether responses were
      different between men and women. 19 women and 18 men performed a controlled
      transfer task. Surface electromyograms from bilateral sites over 6 back extensor
      compartments and 6 abdominal wall muscle sites were analyzed using principal
      component analysis. Key features were extracted from the measured
      electromyographic waveforms capturing amplitude and temporal variations among
      muscle sites. Three features explained 97% of the variance. Scores for each
      feature were computed for each measured waveform and analysis of variance found
      significant (p<.05) muscle main effects and a sex by muscle interaction. For the
      back extensors, post hoc analysis revealed that upper and more medial sites were
      recruited to higher amplitudes, medial sites responded to flexion moments, and
      the more lateral sites responded to lateral flexion moments. Women had more
      differences among muscle sites than men for the lateral flexion moment feature.
      For the abdominal wall muscles the oblique muscles responded with synergies
      related to fiber orientation, with women having higher amplitudes and more
      responsiveness to the lateral flexion moment than men. Synergies between the
      abdominal and back extensor sites as the moment demands change are discussed.
      These findings illustrate differential activation among erector spinae
      compartments and abdominal wall muscle sites supporting a highly organized
      pattern of response to bidirectional external moments with asynchronies more
      apparent in women.

PMID- 22406503
TI  - Interpersonal and intrapersonal coordinative modes for joint and single task
      performance.
AB  - In recent years, research in the field of social interactions has focused on the
      exploration of the coordinative structures that substantiate joint task
      performance. The current project explores whether interpersonal coordination
      during joint task performance gives rise to a joint coordinative structure across
      individuals, and whether such coordinative structures are affected by task
      demands. Principal component analysis (PCA) is used to identify relevant
      interpersonal and intrapersonal coordinative modes for the single and joint
      performance of a supra-postural task, which varied along its precision and role
      demands. In addition, cross-recurrence quantification analysis (CRQA) was
      combined with PCA in order to quantify the degree and stability of interpersonal
      coordination across intrapersonal coordinative modes. Results indicate that the
      composition and number of coordinative modes varied for joint compared to single
      performance, and that interpersonal coordination across the first coordinative
      mode increased in degree and stability for joint compared to single performance.
      Overall, these findings indicate that joint coordinative structures are affected
      by the nature of the task performed and the constraints it places on joint and
      single performance.

PMID- 22406504
TI  - Inhibition of transient receptor potential melastain 7 channel increases HSCs
      apoptosis induced by TRAIL.
AB  - AIMS: Transient receptor potential melastain 7 (TRPM7) channels are known to have
      a fundamental role in many cellular processes and pathology of various diseases.
      The objective of this study was to investigate the potential relationship between
      TRPM7 and the apoptosis of hepatic stellate cells (HSCs) induced by TNF-related
      apoptosis inducing-ligand (TRAIL). MAIN METHODS: In this study, using a
      combination of Western blotting, RT-PCR and flow cytometric analysis, we
      investigated the influence and potential function of TRPM7 channels on the
      apoptosis induced by TRAIL in HSCs which is the key cell of formation of
      extracellular matrix (ECM) and is also the core link of occurrence of hepatic
      fibrosis (HF). KEY FINDINGS: We observed significant expression of TRPM7 mRNA and
      protein in HSCs. Suppression of TRPM7 channels by 2-aminoethoxydiphenyl borate (2
      APB) or Gd3+ not only markedly eliminated TRPM7 expression, but also increased
      the apoptosis of HSCs induced by TRAIL, a major apoptosis stimulator of HSCs.
      SIGNIFICANCE: Our findings strongly suggest that TRPM7 channels are involved in
      the apoptosis of HSCs induced by TRAIL, probably by regulating the sensitivity of
      HSCs to TRAIL.

PMID- 22406505
TI  - Muscarinic cholinergic signaling in cervical cancer cells affects cell motility
      via ERK1/2 signaling.
AB  - AIMS: The etiology of cervical cancer depends primarily on infection with human
      papillomaviruses, but tobacco smoking is the most important behavioral risk
      factor for this cancer. Therefore, we have previously confirmed involvement of
      nicotinic acetylcholine receptors (nAChRs) in cervical cancer biology. In order
      to comprehensively evaluate the role of cholinergic signaling in cervical cells,
      we have addressed additional participation of muscarinic acetylcholine receptors
      (mAChRs). MAIN METHODS: We have studied the expression of mAChRs and cholinergic
      system components by reverse transcription PCR and Western blots, the motility of
      cervical cancer cells in cell culture, and the signaling from mAChRs via the
      ERK1/2 signaling pathway. KEY FINDINGS: The cervical cancer cells HeLa, SiHa and
      CaSki express four of the five mAChRs, M1, M3, M4, and M5, and the acetylcholine
      (ACh) synthesizing and degrading enzymes choline acetyltransferase (ChAT),
      acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), and vesicular ACh
      transporter (VAChT). mAChR-dependent signaling induces cervical cell motility,
      which requires ERK1/2 activation, and could be abrogated by mAChR antagonists.
      SIGNIFICANCE: The epidemiological finding that tobacco smoke raises the
      prevalence of cervical cancer has led to analysis of the cholinergic signaling in
      cervical biology and carcinogenesis. Cervical cancer cells express several nAChRs
      and mAChRs, whose activation leads to changes of cellular properties such as
      increased motility and proliferation that favor a carcinogenic phenotype. The
      signaling involves intracellular phosphorylation cascades including ERK1/2.

PMID- 22406507
TI  - Polyethylene glycol-containing polyurethane hydrogel coatings for improving the
      biocompatibility of neural electrodes.
AB  - The instability of the interface between chronically implanted neuroprosthetic
      devices and neural tissue is a major obstacle to the long-term use of such
      devices in clinical practice. In this study, we investigate the feasibility of
      polyethylene glycol (PEG)-containing polyurethane (PU) hydrogel as coatings for
      polydimethylsiloxane (PDMS)-based neural electrodes in order to achieve a stable
      neural interface. The influence of PU hydrogel coatings on electrode
      electrochemical behaviour was investigated. Importantly, the biocompatibility of
      PU hydrogel coatings was evaluated in vitro and in vivo. Changes in the
      electrochemical impedance of microelectrodes with PU coatings were negligible.
      The amount of protein adsorption on the PDMS substrate was reduced by 93% after
      coating. Rat pheochromocytoma (PC12) cells exhibited more and longer neurites on
      PU films than on PDMS substrates. Furthermore, PDMS implants with (n=10) and
      without (n=8) PU coatings were implanted into the cortex of rats and the tissue
      response to the implants was evaluated 6 weeks post-implantation. GFAP staining
      for astrocytes and NeuN staining for neurons revealed that PU coatings attenuated
      glial scarring and reduced the neuronal cell loss around the implants. All of
      these findings suggest that PU hydrogel coating is feasible and favourable for
      neural electrode applications.

PMID- 22406506
TI  - Formulation and characterization of poloxamine-based hydrogels as tissue
      sealants.
AB  - In situ cross linkable polyethylene glycol (PEG)-based polymers play an
      increasing role in surgical practice as sealants that provide a barrier to
      fluid/gas leakage and adhesion formation. This study investigated the gelation
      behavior and physical properties of hydrogels formed from homogeneous and blended
      solutions of two acrylated poloxamines (Tetronics(r) T1107 and T904) of various
      molecular weights and hydrophilic/lipophilic balances relative to a PEG control.
      Hydrogels were formed by reverse thermal gelation at physiological temperature
      (T1107-containing formulations) and covalent crosslinking by Michael-type
      addition with dithiothreitol. All poloxamine-based hydrogels exhibited
      thermosensitive behavior and achieved significantly reduced swelling, increased
      tensile properties and increased tissue bond strength relative to the PEG
      hydrogel at physiological temperature. Swelling and tensile properties of all
      poloxamine-based hydrogels were significantly greater at 37 degrees C relative to
      4 degrees C, suggesting that their improved physical properties derive from
      cooperative crosslinking by both noncovalent and covalent mechanisms. Poloxamine
      based hydrogels were cytocompatible and underwent hydrolytic degradation over 2
      5weeks, depending on their T1107/T904 composition. In conclusion, select
      poloxamine-based hydrogels possess a number of properties potentially beneficial
      to tissue sealant applications, including a substantial increase in viscosity
      between room/physiological temperatures, resistance to cell adhesion and
      maintenance of a stable volume during equilibration.

PMID- 22406508
TI  - Magnetic targeting of surface-modified superparamagnetic iron oxide nanoparticles
      yields antibacterial efficacy against biofilms of gentamicin-resistant
      staphylococci.
AB  - Biofilms on biomaterial implants are hard to eradicate with antibiotics due to
      the protection offered by the biofilm mode of growth, especially when caused by
      antibiotic-resistant strains. Superparamagnetic iron oxide nanoparticles (SPIONs)
      are widely used in various biomedical applications, such as targeted drug
      delivery and magnetic resonance imaging. Here, we evaluate the hypothesis that
      SPIONs can be effective in the treatment of biomaterial-associated infection.
      SPIONs can be targeted to the infection site using an external magnetic field,
      causing deep penetration in a biofilm and possibly effectiveness against
      antibiotic-resistant strains. We report that carboxyl-grafted SPIONs,
      magnetically concentrated in a biofilm, cause an approximately 8-fold higher
      percentage of dead staphylococci than does gentamicin for a gentamicin-resistant
      strain in a developing biofilm. Moreover, magnetically concentrated carboxyl
      grafted SPIONs cause bacterial killing in an established biofilm. Thus magnetic
      targeting of SPIONs constitutes a promising alternative for the treatment of
      costly and recalcitrant biomaterial-associated infections by antibiotic-resistant
      strains.

PMID- 22406509
TI  - Neurophysiological impairment in emotional face processing is associated with low
      extraversion in schizophrenia.
AB  - Patients with schizophrenia have low extraversion and high neuroticism. These
      personality traits affect the everyday life of patients with schizophrenia,
      making it important to investigate neurobiological basis of personality traits.
      In healthy people, extraversion is associated with hemodynamic responses in the
      amygdala and electrophysiological brain activity such as event-related potential
      and event-related desynchronization during emotional face processing. Patients
      with schizophrenia show abnormal neural activity during emotional face
      processing, such as an N170 amplitude reduction. However, few studies to date
      have reported an association between personality traits and neural activity
      during emotional face processing in schizophrenia. In the present study, we
      examined N170 during emotional face processing, and association with personality
      traits in patients with schizophrenia. Fifteen male patients with chronic
      schizophrenia and 15 healthy male subjects participated in this study. Patients
      with schizophrenia had reduced N170 amplitudes (p=0.007). While healthy subjects
      had increased N170 amplitudes in response to emotional faces compared with
      neutral faces (p=0.003), patients with schizophrenia showed no difference in N170
      amplitudes between emotional and neutral faces (p=0.60). Reduced N170 amplitude
      in response to neutral faces was correlated with low extraversion scores in
      patients with schizophrenia (r(s)=-0.69, p=0.005). The abnormal N170 and its
      association with extraversion in schizophrenia were found at the right rather
      than the left posterior temporal electrode. An abnormal N170 in schizophrenia may
      reflect impairments in the structural encoding of emotional faces, and
      indiscrimination between emotional and neutral faces at this stage of information
      processing. The association between abnormal N170 amplitudes and extraversion
      suggests that abnormal neural activity in the early stages of emotional face
      processing may underlie low extraversion characteristic of schizophrenia.

PMID- 22406510
TI  - Pain, mind, and movement: unraveling models, shifting paradigms, and the social
      dimension.

PMID- 22406511
TI  - Testosterone and farnesoid X receptor agonist INT-747 counteract high fat diet
      induced bladder alterations in a rabbit model of metabolic syndrome.
AB  - In the male, metabolic syndrome (MetS) is associated to an increased risk of
      benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). A
      recently established rabbit model of high fat diet (HFD)-induced MetS showed
      hypogonadism and the presence of prostate gland alterations, including
      inflammation, hypoxia and fibrosis. The present study investigated whether HFD
      induced MetS might also alter bladder structure and function. Testosterone and
      the farnesoid X receptor (FXR) agonist INT-747, were evaluated for possible
      effects on HFD bladder. MetS rabbits develop bladder alterations, including
      fibrosis (reduced muscle/fiber ratio), hypoxia [2-fold increase as compared to
      regular diet (RD) group], low-grade inflammation (increased leukocyte
      infiltration and inflammatory markers) and RhoA/ROCK hyperactivity. Bladder
      strips from HFD rabbits, pre-contracted with carbachol, showed an overactive
      response to the selective ROCK inhibitor Y-27632. All these HFD-induced bladder
      alterations were partially blunted by testosterone and almost completely reverted
      by INT-747. Both treatments prevented some MetS features (glucose intolerance and
      visceral fat increase), thus suggesting that their effects on bladder could be
      ascribed to an improvement of the metabolic and/or hypogonadal state. However, a
      pathogenetic role for hypogonadism has been ruled out as GnRH analog-induced
      hypogonadal rabbits, fed a regular diet, did not show any detectable bladder
      alterations. In addition, INT-747 did not revert the MetS-induced hypogonadal
      state. FXR mRNA was highly expressed in rabbit bladder and positively associated
      with visceral fat increase. A direct effect of INT-747 on bladder smooth muscle
      was further suggested by inhibition of RhoA/ROCK-mediated activity by in vitro
      experiments on isolated cells. In conclusion, HFD-related MetS features are
      associated to bladder derangements, which are ameliorated by testosterone or INT
      747 administration. INT-747 showed the most marked effects in counteracting MetS
      related RhoA/ROCK overactivity, thus opening novel therapeutic opportunities for
      this drug.

PMID- 22406512
TI  - A flow-modulated comprehensive gas chromatography-mass spectrometry method for
      the analysis of fatty acid profiles in marine and biological samples.
AB  - The present investigation is focused on the development of a flow-modulator (FM)
      comprehensive 2D GC (GC*GC)-quadrupole mass spectrometry (qMS) approach, for the
      analysis of fatty acids. A recently developed flow modulator interfaced an apolar
      polar column set, and was used for the first time with a mass spectrometer.
      Method development was achieved by using a standard mixture, containing fatty
      acid methyl esters (FAMEs). The total run time was approx. 40 min, thus
      relatively rapid. The optimized FM GC*GC-qMS method was applied to marine and
      biological FAMEs. Validation parameters such as intra-day and inter-day
      repeatability, limits of identification (mass spectral quality was evaluated at
      various FAME concentrations), and quantification were measured. Peak assignment
      was performed using pure standard compounds (when available), linear retention
      indices (LRIs), a dedicated FAME MS database, and specific bidimensional
      chromatogram positions. The MS database contained one-dimensional LRI
      information, exploited as a filter during the MS database search procedure. A
      good agreement was observed between database LRI values, and those calculated on
      the twin-column set. The FM GC*GC-qMS method can be considered as a valid
      counterpart, with respect to cryogenically modulated GC*GC, in the fatty acid
      field of research.

PMID- 22406513
TI  - Improving selectivity in multimodal chromatography using controlled pH gradient
      elution.
AB  - Externally generated pH gradients are employed on a multimodal cation exchange
      chromatographic resin to improve the selectivity for a mixture of model proteins.
      By combining controlled pH gradients with the unique selectivities arising from
      the multiple interaction types exhibited by the multimodal resin, the separation
      of the protein mixture is significantly improved as compared to linear salt
      gradient operation. Several gradient conditions are explored and a shallow
      gradient from pH 3.8 to 5.5 is shown to be able to resolve the proteins. This
      work provides proof of concept for the use of pH gradients in multimodal
      chromatography and sets the stage for future applications.

PMID- 22406514
TI  - A recent evaluation of the lethal potencies of ammodytoxins.
AB  - Ammodytoxin A (AtxA) is the most toxic secreted phospholipase A(2) of the three
      isotoxins with presynaptic neurotoxicity, isolated from the venom of the nose
      horned viper (Vipera ammodytes ammodytes), with an LD(50) of 21 MUg/kg in mice.
      The toxic potencies of two other isoforms have been re-evaluated using highly
      purified recombinant proteins, with their intraperitoneal LD(50)s determined as
      960 MUg/kg for AtxB and 310 MUg/kg for AtxC. AtxB and AtxC differ from AtxA in
      only three and two amino acid residues, respectively.

PMID- 22406515
TI  - Quantification of domoic acid in shellfish samples by capillary electrophoresis
      based enzyme immunoassay with electrochemical detection.
AB  - A new method was developed to quantify domoic acid by capillary electrophoresis
      based enzyme immunoassay (CE-EIA) with electrochemical (EC) detection. The method
      was based on noncompetitive immunoreaction between free domoic acid antigen (Ag)
      and excessive amount of horseradish peroxidase (HRP)-labeled antidomoic acid
      antibody tracer (Ab*) in liquid phase. Then the bound enzyme-labeled complex (Ab*
      Ag) and unbound Ab* were separated by CE, and the system of HRP catalyzing
      H(2)O(2)/o-aminophenol (OAP) reaction was adopted for EC detection. Using CE-EIA
      with EC detection, equilibrium was reached in 30 min, and the analytical results
      were obtained within a further 5 min. The linear range and the detection limit
      were 0.1-50 ng/mL and 0.02 ng/mL, respectively. Analytes recoveries were 89.6
      105.8%. The sensitivity of the method was 16 times greater than that of enzyme
      linked immunosorbent assay (ELISA). The developed method was applied to
      quantitatively analysis of domoic acid in contaminated shellfish samples with
      rapid and simple pretreatment, and the results were consistent with the same
      samples analyzed through ELISA. The CE-EIA with EC detection provides a valid and
      sensitive analytical approach, not previously available, for determination of
      domoic acid in shellfish samples.

PMID- 22406517
TI  - Serum levels of angiopoietin-related growth factor (AGF) are increased in
      polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a frequent reproductive and
      metabolic disorder associated with insulin resistance. Recently, angiopoietins
      were identified in the systemic circulation and have been designated
      angiopoietinlike proteins (ANGPTL). More recently, it is shown that angiopoietin
      related growth factor (AGF, also called ANGPTL6) directly regulate lipid,
      glucose, and energy metabolism independent of angiogenic effects in animal
      studies. The aim of this study was to determine whether there is an association
      between AGF and PCOS. METHODS: The study included 55 [corrected] patients with
      PCOS and 30 healthy control women. We analyzed serum levels of AGF and other
      biochemical and anthropometric markers in all the subjects. RESULTS: This study
      showed that serum AGF levels were significantly higher in the subjects with PCOS
      (102.28 ng/mL) than those in the healthy control group (63.08 ng/mL; P < 0.001).
      Body mass index (24.33 vs 22.11 kg/m; P = 0.017), free testosterone (2.81 vs 2.17
      pmol/L; P = 0.009), androstenedione (3.28 vs 2.92 nmol/L; P = 0.033), 17
      hydroxyprogesterone (2.72 vs 2.09 ng/mL; P = 0.039), homeostasis model of
      assessment-insulin resistance (2.65 vs 1.9; P = 0.016), and fasting glucose
      (107.09 vs 96.18 mmol/L; P = 0.001) were found significantly higher in PCOS group
      than in control group. But there was no correlation between AGF and these
      parameters in PCOS group. In addition, no correlation between the AGF and other
      distinctive features of PCOS was found. CONCLUSIONS: Serum AGF levels were
      paradoxically increased in patients with PCOS in comparison with data of animal
      experiments. Further studies are needed to better elucidate the physiologic
      significance of circulating AGF in human disease.

PMID- 22406518
TI  - A diversity-oriented synthesis approach to macrocycles via oxidative ring
      expansion.
AB  - Macrocycles are key structural elements in numerous bioactive small molecules and
      are attractive targets in the diversity-oriented synthesis of natural product
      based libraries. However, efficient and systematic access to diverse collections
      of macrocycles has proven difficult using classical macrocyclization reactions.
      To address this problem, we have developed a concise, modular approach to the
      diversity-oriented synthesis of macrolactones and macrolactams involving
      oxidative cleavage of a bridging double bond in polycyclic enol ethers and
      enamines. These substrates are assembled in only four or five synthetic steps and
      undergo ring expansion to afford highly functionalized macrocycles bearing
      handles for further diversification. In contrast to macrocyclization reactions of
      corresponding seco acids, the ring expansion reactions are efficient and
      insensitive to ring size and stereochemistry, overcoming key limitations of
      conventional approaches to systematic macrocycle synthesis. Cheminformatic
      analysis indicates that these macrocycles access regions of chemical space that
      overlap with natural products, distinct from currently targeted synthetic drugs.

PMID- 22406519
TI  - A fungal ketoreductase domain that displays substrate-dependent
      stereospecificity.
AB  - Iterative highly reducing polyketide synthases from filamentous fungi are the
      most complex and enigmatic type of polyketide synthase discovered to date. Here
      we uncover an unusual degree of programming by the hypothemycin highly reducing
      polyketide synthase, in which a single ketoreductase domain shows
      stereospecificity that is controlled by substrate length. Mapping of the
      structural domains responsible for this feature allowed for the biosynthesis of
      an unnatural diastereomer of the natural product dehydrozearalenol.

PMID- 22406516
TI  - Pancreatic ductal adenocarcinoma:  a review of immunologic aspects.
AB  - With the continued failures of both early diagnosis and treatment options for
      pancreatic cancer, it is now time to comprehensively evaluate the role of the
      immune system on the development and progression of pancreatic cancer. It is
      important to develop strategies that harness the molecules and cells of the
      immune system to treat this disease. This review will focus primarily on the role
      of immune cells in the development and progression of pancreatic ductal
      adenocarcinoma and to evaluate what is known about the interaction of immune
      cells with the tumor microenvironment and their role in tumor growth and
      metastasis. We will conclude with a brief discussion of therapy for pancreatic
      cancer and the potential role for immunotherapy. We hypothesize that the role of
      the immune system in tumor development and progression is tissue specific. Our
      hope is that better understanding of this process will lead to better treatments
      for this devastating disease.

PMID- 22406520
TI  - A new pH-sensitive rectifying potassium channel in mitochondria from the
      embryonic rat hippocampus.
AB  - Patch-clamp single-channel studies on mitochondria isolated from embryonic rat
      hippocampus revealed the presence of two different potassium ion channels: a
      large-conductance (288+/-4pS) calcium-activated potassium channel and second
      potassium channel with outwardly rectifying activity under symmetric conditions
      (150/150mM KCl). At positive voltages, this channel displayed a conductance of
      67.84pS and a strong voltage dependence at holding potentials from -80mV to
      +80mV. The open probability was higher at positive than at negative voltages.
      Patch-clamp studies at the mitoplast-attached mode showed that the channel was
      not sensitive to activators and inhibitors of mitochondrial potassium channels
      but was regulated by pH. Moreover, we demonstrated that the channel activity was
      not affected by the application of lidocaine, an inhibitor of two-pore domain
      potassium channels, or by tertiapin, an inhibitor of inwardly rectifying
      potassium channels. In summary, based on the single-channel recordings, we
      characterised for the first time mitochondrial pH-sensitive ion channel that is
      selective for cations, permeable to potassium ions, displays voltage sensitivity
      and does not correspond to any previously described potassium ion channels in the
      inner mitochondrial membrane. This article is part of a Special Issue entitled:
      17th European Bioenergetics Conference (EBEC 2012).

PMID- 22406521
TI  - Gut microbiome and intestinal barrier failure--the "Achilles heel" in hepatology?

PMID- 22406522
TI  - Dynamics of walking adaptation aftereffects induced in static images of walking
      actors.
AB  - Visual adaptation to walking actions results in subsequent aftereffects that bias
      perception of static images of walkers in different postures so that they are
      interpreted as walking in the opposite direction to the adapting actor. It is not
      clear, however, if the walking aftereffect is comparable to other well studied
      low- and high-level visual aftereffects. We therefore measured the dynamics of
      the walking aftereffect in order to assess the characteristics of the adapting
      mechanism. We found that walking aftereffects showed similar characteristic
      dynamics as for face aftereffects and some motion aftereffects. Walking
      aftereffects could be induced in a broad range of different static images of
      walking actors and were not restricted to images of actors in any particular
      posture. Walking aftereffects increased with adapting stimulus repetition and
      declined over time. The duration of the aftereffect was dependent upon time spent
      observing the adapting stimulus and could be well modelled by a power-law
      function that characterises this relationship in both face and motion
      aftereffects. Increasing the speed of the adapting stimulus by increasing actor
      walk speed increased aftereffect magnitude, as seen for some motion aftereffects.
      The nature of the aftereffects induced by observing walking actors indicates that
      they behave like traditional high-level visual aftereffects.

PMID- 22406523
TI  - A detailed surgical method for mechanical decerebration of the rat.
AB  - Surgical methods currently employed for the mechanical decerebration of a rat are
      only briefly described in the literature; hence, an information void exists for
      researchers wishing to adopt this technique successfully. Decerebration can lead
      to a high rate of mortality owing to cranial bleeding, particularly if the
      operator is inexperienced and uninformed. The illustrated methodology presented
      here describes, in detail, steps in the decerebration process and indicates
      effective approaches, such as reversible occlusion of a carotid artery, the
      combined use of tissue adhesive and haemostatic sponge, and perisurgical
      monitoring of blood pressure, by which to control blood loss and thus maintain
      mean postsurgical blood pressure within acceptable physiological parameters. By
      using this methodology, animal losses can be minimized, particularly in the early
      stages of adoption of the technique, ultimately reducing the numbers required for
      a study of this nature.

PMID- 22406524
TI  - Missed opportunities--low levels of chlamydia retesting at Australian general
      practices, 2008-2009.
AB  - OBJECTIVE: Chlamydia reinfection is common and increases the risk of reproductive
      complications. Guidelines for Australian general practitioners recommend
      retesting 3-12 months after a positive result but not before 6 weeks. The authors
      describe retesting rates among 16-29-year-old patients diagnosed as having
      chlamydia at 25 general practice clinics participating in the Australian
      Collaboration for Chlamydia Enhanced Sentinel Surveillance system. METHODS: The
      authors calculated annual testing and positivity rates for 16-29-year-olds
      attending in 2008-2009, re-attendance and retesting rates within <6 weeks, 1.5-4
      months and 1.5-12 months of a positive test in 2008-2009 and positivity at retest
      (where results were available). Results There were 50,408 individuals (60.4%
      women) who attended in 2008-2009. Annually, 7.4% and 7.3% were tested for
      chlamydia, of whom 9.1% and 8.0% tested positive, respectively. Within 1.5-4
      months of a positive test, 24.6% re-attended and were retested (19% tested
      positive), 31.6% re-attended and were not retested and 43.9% did not re-attend.
      Within 1.5-12 months, 40% re-attended and were retested (16% tested positive),
      40% re-attended and were not retested and 20% did not re-attend. Of individuals
      re-attending in 1.5-12 months but not retested, 50% had re-attended three or more
      times in the period. Within 6 weeks of a positive test, 25% were retested.
      DISCUSSION: A high proportion of 16-29-year-olds re-attended general practices in
      the recommended retest periods, but retesting rates were low and multiple missed
      opportunities were common. The findings highlight the need for strategies such as
      electronic clinician prompts, patient recall systems and promotion of retesting
      guidelines.

PMID- 22406525
TI  - The amino-terminal helix modulates light-activated conformational changes in
      AsLOV2.
AB  - The mechanism of light-triggered conformational change and signaling in light
      oxygen-voltage (LOV) domains remains elusive in spite of extensive investigation
      and their use in optogenetic studies. The LOV2 domain of Avenasativa phototropin
      1 (AsLOV2), a member of the Per-Arnt-Sim (PAS) family, contains a flavin
      mononucleotide chromophore that forms a covalent bond with a cysteine upon
      illumination. This event leads to the release of the carboxy-terminal Jalpha
      helix, the biological output signal. Using mutational analysis, circular
      dichroism, and NMR, we find that the largely ignored amino-terminal helix is a
      control element in AsLOV2's light-activated conformational change. We further
      identify a direct amino-to-carboxy-terminal "input-output" signaling pathway.
      These findings provide a framework to rationalize the LOV domain architecture, as
      well as the signaling mechanisms in both isolated and tandem arrangements of PAS
      domains. This knowledge can be applied in engineering LOV-based photoswitches,
      opening up new design strategies and improving existing ones.

PMID- 22406526
TI  - Time course of DNA adduct formation in peripheral blood granulocytes and
      lymphocytes after drinking alcohol.
AB  - Alcohol consumption is an established risk factor for cancers of the head and
      neck, colorectum, liver and female breast. Acetaldehyde, the primary metabolite
      of ethanol, is suspected to play a major role in alcohol-related carcinogenesis.
      Acetaldehyde binds to DNA resulting in formation of adducts. DNA adducts are
      involved in mutagenesis and carcinogenesis. N (2)-Ethylidenedeoxyguanosine (N (2)
      ethylidene-dGuo) is the major adduct formed in this reaction. Studies have shown
      an association between alcohol drinking and levels of this DNA adduct, suggesting
      its potential use as a biomarker for studying alcohol-related carcinogenesis.
      However, there are no reports on the kinetics of formation and repair of N (2)
      ethylidene-dGuo after alcohol consumption. Therefore, we investigated levels of N
      (2)-ethylidene-dGuo in DNA from human peripheral blood cells at several time
      points after consumption of increasing doses of alcohol. Ten healthy non-smokers
      were recruited and asked to abstain from alcohol consumption except for the study
      doses. The subjects were given measured doses of alcohol once a week for 3 weeks,
      targeting increasing blood alcohol levels. Blood was collected at several time
      points before and after each dose, DNA was isolated from granulocytes and
      lymphocytes and N (2)-ethylidene-dGuo was quantified as its NaBH(3)CN reduction
      product N ( 2 )-ethyldeoxyguanosine by liquid chromatography-electrospray
      ionisation-tandem mass spectrometry. Significant increases in N (2)-ethylidene
      dGuo were observed after all doses and in both cell types. However, there was
      substantial intraindividual variability, indicating that there are other
      important sources of this adduct in peripheral blood DNA. Further studies are
      needed to better understand the origins of N (2)-ethylidene-dGuo in blood cells,
      the exposures it reflects, and thus its potential use as a marker of alcohol's
      genotoxic effects.

PMID- 22406527
TI  - Short-term studies using ceramic scaffolds in lapine model for osteochondral
      defect amelioration.
AB  - This study was undertaken to glean preliminary information on the role of
      triphasic ceramic coated hydroxyapatite (HASi) and biphasic (alpha-tricalcium
      phosphate and hydroxyapatite based) calcium phosphate (BCP) for the development
      of osteochondral constructs. The proposed constructs were tested for performance
      in vitro with rabbit adipose-derived mesenchymal stem cells (RADMSCs) and further
      analysed in vivo in a lapine model for osteochondral defect amelioration.
      Desirable scaffolding architecture ensuring favourable conditions for cell
      attachment, nutrient exchange and neo-tissue organization was achieved by the
      synthesis of porous ceramic blocks and characterizations were carried out using x
      ray diffraction and Fourier transform infrared spectroscopy. The
      cytocompatibility of the scaffold-cell combination product was evaluated using
      microscopy techniques that proved the scaffold to be non-cytotoxic and favourable
      for cell growth and proliferation. Short-term implantation studies were conducted
      with bare cylindrical HASi and BCP scaffolds, press fit deep into the bony bed of
      the median femoral condyles of the rabbit, which resulted in favourable specific
      in vivo response of de novo cartilage-like cells on the surface and sub-surface
      bony trabeculae. The generated pilot data will help to assess the severity of
      proposed procedures before embarking on scaled-up efforts.

PMID- 22406528
TI  - Horny sponges and their affairs: on the phylogenetic relationships of keratose
      sponges.
AB  - The demosponge orders Dictyoceratida and Dendroceratida are historically assigned
      to the keratose (or "horny") sponges, which are mostly devoid of primary skeletal
      elements, but possess an elaborate skeleton of organic fibres instead. This
      paucity of complex mineral skeletal elements makes their unambiguous
      classification and phylogenetic reconstruction based on morphological features
      difficult. Here we present the most comprehensive molecular phylogeny to date for
      the Dendroceratida, Dictyoceratida, and also other sponge orders that largely
      lack a mineral skeleton or skeletal elements at all (i.e. Verongida, Halisarcida,
      Chondrosida), based on independent mitochondrial and nuclear markers. We used
      molecular data to validate the coherence of all recognised orders, families and
      subfamilies that are currently defined using morphological characteristics. We
      discussed the significance of morphological and chemotaxonomic characters for
      keratose sponges, and suggested adapted definitions for the classification of
      dendroceratid, dictyoceratid, and verongid higher taxa. Also, we found that
      chondrosid sponges are non-monophyletic with respect to Halisarcida. Verongida
      and Dendroceratida were monophyletic, however most of their classically
      recognised families were not recovered. This indicated that the current
      distinction between dendritic and mesh-like fibre skeletons is not significant at
      this level of classification. Dysideidae were found to be the sister-group to the
      remaining Dictyoceratida. Irciniidae formed a distinct clade, however Thorectidae
      and Spongiidae could not be separated with the molecular markers used. Finally,
      we are establishing the name Verongimorpha for the clade combining verongid,
      chondrosid and halisarcid taxa and readjust the content of its sister-clade
      Keratosa.

PMID- 22406529
TI  - Adding resolution to ordinal level relationships of tapeworms (Platyhelminthes:
      Cestoda) with large fragments of mtDNA.
AB  - The construction of a stable phylogeny for the Cestoda, indicating the
      interrelationships of recognised orders and other major lineages, has proceeded
      iteratively since the group first received attention from phylogenetic
      systematists. Molecular analyses using nuclear ribosomal RNA gene fragments from
      the small (ssrDNA) and large (lsrDNA) subunits have been used to test competing
      evolutionary scenarios based on morphological data but could not arbitrate
      between some key conflicting hypotheses. To the ribosomal data, we have added a
      contiguous fragment of mitochondrial (mt) genome data (mtDNA) of partial nad1
      trnN-trnP-trnI-trnK-nad3-trnS-trnW-cox1-trnT-rrnL-trnC-partial rrnS, spanning
      4034-4447 bp, where new data for this region were generated for 18 species.
      Bayesian analysis of mtDNA and rDNA as nucleotides, and where appropriate as
      amino acids, demonstrated that these two classes of genes provide complementary
      signal across the phylogeny. In all analyses, except when using mt amino acids
      only, the Gyrocotylidea is sister group to all other Cestoda
      (Nephroposticophora), and Amphilinidea forms the sister group to the Eucestoda.
      However, an earliest-diverging position of Amphilinidea is strongly supported in
      the mt amino acid analysis. Amphilinidea exhibit a unique tRNA arrangement (nad1
      trnI-trnL2-trnP-trnK-trnV-trnA-trnN-nad3), whereas Gyrocotylidea shares that of
      the derived lineages, providing additional evidence of the uniqueness of
      amphilinid genes and genomes. The addition of mtDNA to the rDNA genes supported
      the Caryophyllidea as the sister group to (Spathebothriidea+remaining Eucestoda),
      a hypothesis consistently supported by morphology. This relationship suggests a
      history of step-wise evolutionary transitions from simple monozoic, unsegmented
      tapeworms to the more familiar polyzoic, externally segmented (strobilate) forms.
      All our data partitions recovered Haplobothriidea as the sister group to
      Diphyllobothriidae. The sister-group relationship between Diphyllidea and
      Trypanorhyncha, as previously established using rDNA, is not supported by the mt
      data, although it is supported by the combined mt and rDNA analysis. With regards
      to the more derived taxa, in all except the mt amino acid analysis, the following
      topology is supported: (Bothriocephalidea (Litobothriidea (Lecanicephalidea
      (Rhinebothriidea (Tetraphyllidea, (Acanthobothrium, Proteocephalidea),
      (Nippotaeniidea, Mesocestoididae, Tetrabothriidea, Cyclophyllidea)))))), where
      the Tetraphyllidea are paraphyletic. Evidence from the mt data provides strong
      (nucleotides) to moderate (amino acids) support for Tetraphyllidea forming a
      group to the inclusion of Proteocephalidea, with the latter consistently forming
      the sister group to Acanthobothrium. The interrelationships among Nippotaeniidea,
      Mesocestoididae, Tetrabothriidea and Cyclophyllidea remain ambiguous and require
      further systematic attention. Mitochondrial and nuclear rDNA data provide
      conflicting signal for certain parts of the cestode tree. In some cases mt data
      offer results in line with morphological evidence, such as the interrelationships
      of the early divergent lineages. Also, Tetraphyllidea, although remaining
      paraphyletic with the inclusion of the Proteocephalidea, does not include the
      most derived cestodes; a result which has consistently been obtained with rDNA.

PMID- 22406530
TI  - Phylogeny of the Asian Eutropis (Squamata: Scincidae) reveals an 'into India'
      endemic Indian radiation.
AB  - Recent generic rearrangement of the circumtropical distributed skink genus
      'Mabuya' has raised a lot of debate. According to this molecular phylogeny based
      rearrangement, the tropical Asian members of this genus have been assigned to
      Eutropis. However, in these studies the Asian members of 'Mabuya' were largely
      sampled from Southeast (SE) Asia with very few species from Indian subcontinent.
      To test the validity of this assignment and to determine the evolutionary origin
      of Indian members of this group we sequenced one nuclear and two mitochondrial
      genes from most of the species from the Indian subregion. The nuclear and
      mitochondrial trees generated from these sequences confirmed the monophyly of the
      tropical Asian Eutropis. Furthermore, in the tree based on the combined
      mitochondrial and nuclear dataset an endemic Indian radiation was revealed that
      was nested within a larger Asian clade. Results of dispersal-vicariance analysis
      and molecular dating suggested an initial dispersal of Eutropis from SE Asia into
      India around 5.5-17 million years ago, giving rise to the extant members of the
      endemic Indian radiation. This initial dispersal was followed by two back
      dispersals from India into SE Asia. We also discuss the relationships within the
      endemic Indian radiation and its taxonomic implications.

PMID- 22406531
TI  - G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression
      in human breast cancer.
AB  - Breast cancers are highly heterogeneous but can be grouped into subtypes based on
      several criteria, including level of expression of certain markers. Claudin-low
      breast cancer (CLBC) is associated with early metastasis and resistance to
      chemotherapy, while gene profiling indicates it is characterized by the
      expression of markers of epithelial-mesenchymal transition (EMT) - a phenotypic
      conversion linked with metastasis. Although the epigenetic program controlling
      the phenotypic and cellular plasticity of EMT remains unclear, one contributor
      may be methylation of the E-cadherin promoter, resulting in decreased E-cadherin
      expression, a hallmark of EMT. Indeed, reduced E-cadherin often occurs in CLBC
      and may contribute to the early metastasis and poor patient survival associated
      with this disease. Here, we have determined that methylation of histone H3 on
      lysine 9 (H3K9me2) is critical for promoter DNA methylation of E-cadherin in
      three TGF-beta-induced EMT model cell lines, as well as in CLBC cell lines.
      Further, Snail interacted with G9a, a major euchromatin methyltransferase
      responsible for H3K9me2, and recruited G9a and DNA methyltransferases to the E
      cadherin promoter for DNA methylation. Knockdown of G9a restored E-cadherin
      expression by suppressing H3K9me2 and blocking DNA methylation. This resulted in
      inhibition of cell migration and invasion in vitro and suppression of tumor
      growth and lung colonization in in vivo models of CLBC metastasis. Our study not
      only reveals a critical mechanism underlying the epigenetic regulation of EMT but
      also paves a way for the development of new treatment strategies for CLBC.

PMID- 22406532
TI  - Niacin and biosynthesis of PGD2by platelet COX-1 in mice and humans.
AB  - The clinical use of niacin to treat dyslipidemic conditions is limited by noxious
      side effects, most commonly facial flushing. In mice, niacin-induced flushing
      results from COX-1-dependent formation of PGD2 and PGE2 followed by COX-2
      dependent production of PGE2. Consistent with this, niacin-induced flushing in
      humans is attenuated when niacin is combined with an antagonist of the PGD2
      receptor DP1. NSAID-mediated suppression of COX-2-derived PGI2 has negative
      cardiovascular consequences, yet little is known about the cardiovascular biology
      of PGD2. Here, we show that PGD2 biosynthesis is augmented during platelet
      activation in humans and, although vascular expression of DP1 is conserved
      between humans and mice, platelet DP1 is not present in mice. Despite this, DP1
      deletion in mice augmented aneurysm formation and the hypertensive response to
      Ang II and accelerated atherogenesis and thrombogenesis. Furthermore, COX
      inhibitors in humans, as well as platelet depletion, COX-1 knockdown, and COX-2
      deletion in mice, revealed that niacin evoked platelet COX-1-derived PGD2
      biosynthesis. Finally, ADP-induced spreading on fibrinogen was augmented by
      niacin in washed human platelets, coincident with increased thromboxane (Tx)
      formation. However, in platelet-rich plasma, where formation of both Tx and PGD2
      was increased, spreading was not as pronounced and was inhibited by DP1
      activation. Thus, PGD2, like PGI2, may function as a homeostatic response to
      thrombogenic and hypertensive stimuli and may have particular relevance as a
      constraint on platelets during niacin therapy.

PMID- 22406533
TI  - Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in
      rats.
AB  - The ability of the liver to regenerate is crucial to protect liver function after
      injury and during chronic disease. Increases in hepatocyte growth factor (HGF) in
      liver sinusoidal endothelial cells (LSECs) are thought to drive liver
      regeneration. However, in contrast to endothelial progenitor cells, mature LSECs
      express little HGF. Therefore, we sought to establish in rats whether liver
      injury causes BM LSEC progenitor cells to engraft in the liver and provide
      increased levels of HGF and to examine the relative contribution of resident and
      BM LSEC progenitors. LSEC label-retaining cells and progenitors were identified
      in liver and LSEC progenitors in BM. BM LSEC progenitors did not contribute to
      normal LSEC turnover in the liver. However, after partial hepatectomy, BM LSEC
      progenitor proliferation and mobilization to the circulation doubled. In the
      liver, one-quarter of the LSECs were BM derived, and BM LSEC progenitors
      differentiated into fenestrated LSECs. When irradiated rats underwent partial
      hepatectomy, liver regeneration was compromised, but infusion of LSEC progenitors
      rescued the defect. Further analysis revealed that BM LSEC progenitors expressed
      substantially more HGF and were more proliferative than resident LSEC progenitors
      after partial hepatectomy. Resident LSEC progenitors within their niche may play
      a smaller role in recovery from partial hepatectomy than BM LSEC progenitors,
      but, when infused after injury, these progenitors engrafted and expanded markedly
      over a 2-month period. In conclusion, LSEC progenitor cells are present in liver
      and BM, and recruitment of BM LSEC progenitors is necessary for normal liver
      regeneration.

PMID- 22406534
TI  - The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells
      regulates lymphocyte trafficking in mice.
AB  - The bioactive lysophospholipid mediator sphingosine-1-phosphate (S1P) promotes
      the egress of newly formed T cells from the thymus and the release of immature B
      cells from the bone marrow. It has remained unclear, however, where and how S1P
      is released. Here, we show that in mice, the S1P transporter spinster homolog 2
      (Spns2) is responsible for the egress of mature T cells and immature B cells from
      the thymus and bone marrow, respectively. Global Spns2-KO mice exhibited marked
      accumulation of mature T cells in thymi and decreased numbers of peripheral T
      cells in blood and secondary lymphoid organs. Mature recirculating B cells were
      reduced in frequency in the bone marrow as well as in blood and secondary
      lymphoid organs. Bone marrow reconstitution studies revealed that Spns2 was not
      involved in S1P release from blood cells and suggested a role for Spns2 in other
      cells. Consistent with these data, endothelia-specific deletion of Spns2 resulted
      in defects of lymphocyte egress similar to those observed in the global Spns2-KO
      mice. These data suggest that Spns2 functions in ECs to establish the S1P
      gradient required for T and B cells to egress from their respective primary
      lymphoid organs. Furthermore, Spns2 could be a therapeutic target for a broad
      array of inflammatory and autoimmune diseases.

PMID- 22406535
TI  - RhoGDI2 suppresses lung metastasis in mice by reducing tumor versican expression
      and macrophage infiltration.
AB  - Half of patients with muscle-invasive bladder cancer develop metastatic disease,
      and this is responsible for most of the deaths from this cancer. Low expression
      of RhoGTP dissociation inhibitor 2 (RhoGDI2; also known as ARHGDIB and Ly-GDI) is
      associated with metastatic disease in patients with muscle-invasive bladder
      cancer. Moreover, a reduction in metastasis is observed upon reexpression of
      RhoGDI2 in xenograft models of metastatic cancer. Here, we show that RhoGDI2
      suppresses lung metastasis in mouse models by reducing the expression of isoforms
      V1 and V3 of the proteoglycan versican (VCAN; also known as chondroitin sulfate
      proteoglycan 2 [CSPG2]). In addition, we found that high versican levels
      portended poor prognosis in patients with bladder cancer. The functional
      importance of tumor expression of versican in promoting metastasis was
      established in in vitro and in vivo studies in mice that implicated a role for
      the chemokine CCL2 (also known as MCP1) and macrophages. Further analysis
      indicated that RhoGDI2 suppressed metastasis by altering inflammation in the
      tumor microenvironment. In summary, we demonstrate what we believe to be a new
      mechanism of metastasis suppression that works by reducing host responses that
      promote metastatic colonization of the lung. Therapeutic targeting of these
      interactions may provide a novel adjuvant strategy for delaying the appearance of
      clinical metastasis in patients.

PMID- 22406536
TI  - An NF-kappaB pathway-mediated positive feedback loop amplifies Ras activity to
      pathological levels in mice.
AB  - Genetic mutations that give rise to active mutant forms of Ras are oncogenic and
      found in several types of tumor. However, such mutations are not clear biomarkers
      for disease, since they are frequently detected in healthy individuals. Instead,
      it has become clear that elevated levels of Ras activity are critical for Ras
      induced tumorigenesis. However, the mechanisms underlying the production of
      pathological levels of Ras activity are unclear. Here, we show that in the
      presence of oncogenic Ras, inflammatory stimuli initiate a positive feedback loop
      involving NF-kappaB that further amplifies Ras activity to pathological levels.
      Stimulation of Ras signaling by typical inflammatory stimuli was transient and
      had no long-term sequelae in wild-type mice. In contrast, these stimuli generated
      prolonged Ras signaling and led to chronic inflammation and precancerous
      pancreatic lesions (PanINs) in mice expressing physiological levels of oncogenic
      K-Ras. These effects of inflammatory stimuli were disrupted by deletion of
      inhibitor of NF-kappaB kinase 2 (IKK2) or inhibition of Cox-2. Likewise,
      expression of active IKK2 or Cox-2 or treatment with LPS generated chronic
      inflammation and PanINs only in mice expressing oncogenic K-Ras. The data support
      the hypothesis that in the presence of oncogenic Ras, inflammatory stimuli
      trigger an NF-kappaB-mediated positive feedback mechanism involving Cox-2 that
      amplifies Ras activity to pathological levels. Because a large proportion of the
      adult human population possesses Ras mutations in tissues including colon,
      pancreas, and lung, disruption of this positive feedback loop may be an important
      strategy for cancer prevention.

PMID- 22406537
TI  - A multimodal RAGE-specific inhibitor reduces amyloid beta-mediated brain disorder
      in a mouse model of Alzheimer disease.
AB  - In Alzheimer disease (AD), amyloid beta peptide (Abeta) accumulates in plaques in
      the brain. Receptor for advanced glycation end products (RAGE) mediates Abeta
      induced perturbations in cerebral vessels, neurons, and microglia in AD. Here, we
      identified a high-affinity RAGE-specific inhibitor (FPS-ZM1) that blocked Abeta
      binding to the V domain of RAGE and inhibited Abeta40- and Abeta42-induced
      cellular stress in RAGE-expressing cells in vitro and in the mouse brain in vivo.
      FPS-ZM1 was nontoxic to mice and readily crossed the blood-brain barrier (BBB).
      In aged APPsw/0 mice overexpressing human Abeta-precursor protein, a transgenic
      mouse model of AD with established Abeta pathology, FPS-ZM1 inhibited RAGE
      mediated influx of circulating Abeta40 and Abeta42 into the brain. In brain, FPS
      ZM1 bound exclusively to RAGE, which inhibited beta-secretase activity and Abeta
      production and suppressed microglia activation and the neuroinflammatory
      response. Blockade of RAGE actions at the BBB and in the brain reduced Abeta40
      and Abeta42 levels in brain markedly and normalized cognitive performance and
      cerebral blood flow responses in aged APPsw/0 mice. Our data suggest that FPS-ZM1
      is a potent multimodal RAGE blocker that effectively controls progression of
      Abeta-mediated brain disorder and that it may have the potential to be a disease
      modifying agent for AD.

PMID- 22406538
TI  - EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is
      found in human tumors.
AB  - Epstein-Barr virus (EBV) persistently infects more than 90% of the human
      population and is etiologically linked to several B cell malignancies, including
      Burkitt lymphoma (BL), Hodgkin lymphoma (HL), and diffuse large B cell lymphoma
      (DLBCL). Despite its growth transforming properties, most immune-competent
      individuals control EBV infection throughout their lives. EBV encodes various
      oncogenes, and of the 6 latency-associated EBV-encoded nuclear antigens, only
      EBNA3B is completely dispensable for B cell transformation in vitro. Here, we
      report that infection with EBV lacking EBNA3B leads to aggressive, immune-evading
      monomorphic DLBCL-like tumors in NOD/SCID/gammac-/- mice with reconstituted human
      immune system components. Infection with EBNA3B-knockout EBV (EBNA3BKO) induced
      expansion of EBV-specific T cells that failed to infiltrate the tumors. EBNA3BKO
      infected B cells expanded more rapidly and secreted less T cell-chemoattractant
      CXCL10, reducing T cell recruitment in vitro and T cell-mediated killing in vivo.
      B cell lines from 2 EBV-positive human lymphomas encoding truncated EBNA3B
      exhibited gene expression profiles and phenotypic characteristics similar to
      those of tumor-derived lines from the humanized mice, including reduced CXCL10
      secretion. Screening EBV-positive DLBCL, HL, and BL human samples identified
      additional EBNA3B mutations. Thus, EBNA3B is a virus-encoded tumor suppressor
      whose inactivation promotes immune evasion and virus-driven lymphomagenesis.

PMID- 22406540
TI  - Prenatal diagnosis of a family affected by brachydactyly type A1 with a mutation
      in IHH:  a useful lesson.

PMID- 22406539
TI  - Integrated control of axonemal dynein AAA(+) motors.
AB  - Axonemal dyneins are AAA(+) enzymes that convert ATP hydrolysis to mechanical
      work. This leads to the sliding of doublet microtubules with respect to each
      other and ultimately the generation of ciliary/flagellar beating. However, in
      order for useful work to be generated, the action of individual dynein motors
      must be precisely controlled. In addition, cells modulate the motility of these
      organelles through a variety of second messenger systems and these signals too
      must be integrated by the dynein motors to yield an appropriate output. This
      review describes the current status of efforts to understand dynein control
      mechanisms and their connectivity focusing mainly on studies of the outer dynein
      arm from axonemes of the unicellular biflagellate green alga Chlamydomonas.

PMID- 22406541
TI  - Colorectal surgery: current practice & future developments.

PMID- 22406543
TI  - Integration time for the perception of depth from motion parallax.
AB  - The perception of depth from relative motion is believed to be a slow process
      that "builds-up" over a period of observation. However, in the case of motion
      parallax, the potential accuracy of the depth estimate suffers as the observer
      translates during the viewing period. Our recent quantitative model for the
      perception of depth from motion parallax proposes that relative object depth (d)
      can be determined from retinal image motion (dtheta/dt), pursuit eye movement
      (dalpha/dt), and fixation distance (f) by the formula: d/f~dtheta/dalpha. Given
      the model's dynamics, it is important to know the integration time required by
      the visual system to recover dalpha and dtheta, and then estimate d. Knowing the
      minimum integration time reveals the incumbent error in this process. A depth
      phase discrimination task was used to determine the time necessary to perceive
      depth-sign from motion parallax. Observers remained stationary and viewed a
      briefly translating random-dot motion parallax stimulus. Stimulus duration varied
      between trials. Fixation on the translating stimulus was monitored and enforced
      with an eye-tracker. The study found that relative depth discrimination can be
      performed with presentations as brief as 16.6 ms, with only two stimulus frames
      providing both retinal image motion and the stimulus window motion for pursuit
      (mean range=16.6-33.2 ms). This was found for conditions in which, prior to
      stimulus presentation, the eye was engaged in ongoing pursuit or the eye was
      stationary. A large high-contrast masking stimulus disrupted depth-discrimination
      for stimulus presentations less than 70-75 ms in both pursuit and stationary
      conditions. This interval might be linked to ocular-following response eye
      movement latencies. We conclude that neural mechanisms serving depth from motion
      parallax generate a depth estimate much more quickly than previously believed. We
      propose that additional sluggishness might be due to the visual system's attempt
      to determine the maximum dtheta/dalpha ratio for a selection of points on a
      complicated stimulus.

PMID- 22406542
TI  - Methanotrophic communities of Saanich Inlet: a microcosm perspective.
AB  - Saanich Inlet (British Columbia, Canada) is a seasonally anoxic fjord
      characterized by high rates of both methane production and consumption. In this
      study, the diversity of microbial populations residing in intermediate waters,
      characterized by having a high methane content, was assessed using CH(4)
      microcosm experiments coupled with PCR surveys of phylogenetic (16S rRNA gene)
      and functional gene markers (pmoA and fhcD genes). The experiments revealed that
      bacteria represented by sequences affiliated with Methylomicrobium within the
      Methylococcales, Methylophaga and Cycloclasticus within the Thiotrichales, and
      uncultured Planctomycetes were enriched in response to CH(4) addition.

PMID- 22406544
TI  - Use of speed cues in the detection of moving objects by moving observers.
AB  - When an observer moves through an environment containing stationary and moving
      objects, he or she must be able to determine which objects are moving relative to
      the others in order to navigate successfully and avoid collisions. We
      investigated whether image speed can be used as a cue to detect a moving object
      in the scene. Our results show that image speed can be used to detect moving
      objects as long as the object is moving sufficiently faster or slower than it
      would if it were part of the stationary scene.

PMID- 22406545
TI  - EMT as the ultimate survival mechanism of cancer cells.
AB  - Epithelial cancers make up the vast majority of cancer types and, during the
      transition from benign adenoma to malignant carcinoma and metastasis, epithelial
      tumor cells acquire a de-differentiated, migratory and invasive behavior. This
      process of epithelial-mesenchymal transition (EMT) goes along with dramatic
      changes in cellular morphology, the loss and remodeling of cell-cell and cell
      matrix adhesions, and the gain of migratory and invasive capabilities. EMT itself
      is a multistage process, involving a high degree of cellular plasticity and a
      large number of distinct genetic and epigenetic alterations, as fully
      differentiated epithelial cells convert into poorly differentiated, migratory and
      invasive mesenchymal cells. In the past years, a plethora of genes have been
      identified that are critical for EMT and metastasis formation. Notably, the EMT
      process not only induces increased cancer cell motility and invasiveness but also
      allows cancer cells to avoid apoptosis, anoikis, oncogene addiction, cellular,
      senescence and general immune defense. Notably, EMT seems to play a critical role
      in the generation and maintenance of cancer stem cells, highly consistent with
      the notion that metastatic cells carry the ability to initiate new tumors.

PMID- 22406546
TI  - Awake fiberoptic intubation and self-positioning in patients at risk of secondary
      cervical injury: a pilot study.
AB  - BACKGROUND: This study was designed to document the feasibility of self
      positioning after awake fiberoptic intubation of the trachea using primarily
      effective topical anesthesia rather than sedation. METHODS: We investigated 14
      patients (ASA physical status 1 to 3) with a neurosurgical diagnosis of cervical
      instability or at risk of secondary cervical injury, who were scheduled for awake
      fiberoptic intubation and self-positioning prone. Topical anesthesia was
      accomplished using an oropharyngeal spray of lidocaine alone or in combination
      with a transtracheal injection of lidocaine for awake fiberoptic intubation and
      self-positioning prone. Patients evidencing anxiolysis were given midazolam 2 to
      4 mg, i.v.. We assessed the need for sedation, tolerance of the endotracheal
      tube, patient comfort, incidence of coughing or gagging, and changes in heart
      rate, blood pressure, and oxygen saturation. In addition, patients were
      interviewed on the first postoperative day and asked to categorize the experience
      of awake intubation and positioning as a positive, neutral, or negative
      experience, or to have no recall. RESULTS: Eleven of the 14 patients turned
      themselves prone after awake fiberoptic intubation. No additional sedation was
      necessary for accomplishing positioning. Whereas 50% of the patients (7/14)
      showed mostly slight coughing or gagging during fiberoptic intubation, none of
      the patients who were positioned awake had coughing or gagging during tube
      fixation and prone positioning. The technique was unsuccessful in 3 patients.
      None of the patients viewed this as a negative experience. CONCLUSIONS: Our study
      demonstrates that awake fiberoptic intubation and patient self-positioning was
      feasible in this sample of patients at risk of secondary cervical injury. This
      technique may extend the opportunity of continuous neurological monitoring in
      patients with a risk of position-related cervical injury, especially where
      electrophysiological monitoring is not possible or is unavailable.

PMID- 22406547
TI  - NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans.
AB  - In the adult mammalian CNS, chondroitin sulfate proteoglycans (CSPGs) and myelin
      associated inhibitors (MAIs) stabilize neuronal structure and restrict
      compensatory sprouting following injury. The Nogo receptor family members NgR1
      and NgR2 bind to MAIs and have been implicated in neuronal inhibition. We found
      that NgR1 and NgR3 bind with high affinity to the glycosaminoglycan moiety of
      proteoglycans and participate in CSPG inhibition in cultured neurons. Nogo
      receptor triple mutants (Ngr1(-/-); Ngr2(-/-); Ngr3(-/-); which are also known as
      Rtn4r, Rtn4rl2 and Rtn4rl1, respectively), but not single mutants, showed
      enhanced axonal regeneration following retro-orbital optic nerve crush injury.
      The combined loss of Ngr1 and Ngr3 (Ngr1(-/-); Ngr3(-/-)), but not Ngr1 and Ngr2
      (Ngr1(-/-); Ngr2(-/-)), was sufficient to mimic the triple mutant regeneration
      phenotype. Regeneration in Ngr1(-/-); Ngr3(-/-) mice was further enhanced by
      simultaneous ablation of Rptpsigma (also known as Ptprs), a known CSPG receptor.
      Collectively, our results identify NgR1 and NgR3 as CSPG receptors, suggest that
      there is functional redundancy among CSPG receptors, and provide evidence for
      shared mechanisms of MAI and CSPG inhibition.

PMID- 22406548
TI  - Decorrelation and efficient coding by retinal ganglion cells.
AB  - An influential theory of visual processing asserts that retinal center-surround
      receptive fields remove spatial correlations in the visual world, producing
      ganglion cell spike trains that are less redundant than the corresponding image
      pixels. For bright, high-contrast images, this decorrelation would enhance coding
      efficiency in optic nerve fibers of limited capacity. We tested the central
      prediction of the theory and found that the spike trains of retinal ganglion
      cells were indeed decorrelated compared with the visual input. However, most of
      the decorrelation was accomplished not by the receptive fields, but by nonlinear
      processing in the retina. We found that a steep response threshold enhanced
      efficient coding by noisy spike trains and that the effect of this nonlinearity
      was near optimal in both salamander and macaque retina. These results offer an
      explanation for the sparseness of retinal spike trains and highlight the
      importance of treating the full nonlinear character of neural codes.

PMID- 22406549
TI  - VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous
      neurotransmission.
AB  - Synaptic vesicles in the brain harbor several soluble N-ethylmaleimide-sensitive
      factor attachment protein receptor (SNARE) proteins. With the exception of
      synaptobrevin2, or VAMP2 (syb2), which is directly involved in vesicle fusion,
      the role of these SNAREs in neurotransmission is unclear. Here we show that in
      mice syb2 drives rapid Ca(2+)-dependent synchronous neurotransmission, whereas
      the structurally homologous SNARE protein VAMP4 selectively maintains bulk Ca(2+)
      dependent asynchronous release. At inhibitory nerve terminals, up- or
      downregulation of VAMP4 causes a correlated change in asynchronous release.
      Biochemically, VAMP4 forms a stable complex with SNAREs syntaxin-1 and SNAP-25
      that does not interact with complexins or synaptotagmin-1, proteins essential for
      synchronous neurotransmission. Optical imaging of individual synapses indicates
      that trafficking of VAMP4 and syb2 show minimal overlap. Taken together, these
      findings suggest that VAMP4 and syb2 diverge functionally, traffic independently
      and support distinct forms of neurotransmission. These results provide molecular
      insight into how synapses diversify their release properties by taking advantage
      of distinct synaptic vesicle-associated SNAREs.

PMID- 22406550
TI  - Retinotopic activity in V1 reflects the perceived and not the retinal size of an
      afterimage.
AB  - An afterimage looks larger when one fixates on a distant than on a closer
      surface. We show that the retinotopic activity in the primary visual cortex (V1)
      associated with viewing an afterimage is modulated by perceived size, even when
      the size of the retinal image remains constant. This suggests that V1 has an
      important role in size constancy when the viewing distance of the stimulus
      changes.

PMID- 22406551
TI  - Mapping value based planning and extensively trained choice in the human brain.
AB  - Investigations of the underlying mechanisms of choice in humans have focused on
      learning from prediction errors, leaving the computational structure of value
      based planning comparatively underexplored. Using behavioral and neuroimaging
      analyses of a minimax decision task, we found that the computational processes
      underlying forward planning are expressed in the anterior caudate nucleus as
      values of individual branching steps in a decision tree. In contrast, values
      represented in the putamen pertain solely to values learned during extensive
      training. During actual choice, both striatal areas showed a functional coupling
      to ventromedial prefrontal cortex, consistent with this region acting as a value
      comparator. Our findings point toward an architecture of choice in which
      segregated value systems operate in parallel in the striatum for planning and
      extensively trained choices, with medial prefrontal cortex integrating their
      outputs.

PMID- 22406552
TI  - Dense representation of natural odorants in the mouse olfactory bulb.
AB  - In mammals, odorant molecules are thought to activate only a few glomeruli,
      leading to the hypothesis that odor representation in the olfactory bulb is
      sparse. However, the studies supporting this model used anesthetized animals or
      monomolecular odorants at limited concentration ranges. Using optical imaging and
      two-photon microscopy, we found that natural odorants at their native
      concentrations could elicit dense representations in the olfactory bulb. Both
      anesthesia and odorant concentration were found to modulate the representation
      density of natural odorants.

PMID- 22406553
TI  - Antifungal property of dihydrodehydrodiconiferyl alcohol 9'-O-beta-D-glucoside
      and its pore-forming action in plasma membrane of Candida albicans.
AB  - The aims of this study wereto investigate the antifungal activity as a bioactive
      property of dihydrodehydro-diconiferyl alcohol 9'-O-3-D-glucoside (DDDC9G) and
      the mode of action(s) involved in its effect. Antifungal susceptibility testing
      showed that DDDC9G possessed potent antifungal activities toward various fungal
      strains with almost no hemolytic effect. To understand the antifungal
      mechanism(s) of DDDC9G, we conducted the following experiments in this study
      using Candida albicans. Fluorescence experiments using the probe 1,6-eiphenyl-1,
      3, 5-hexatriene (DPH) and propidium iodide suggested that DDDC9G perturbed the
      fungal plasma membrane. Consecutively, the analysis of the transmembrane
      electrical potential (DeltaPsi) with 3, 3'-dipropylthiadicarbocyanine iodide
      [DiSC3(5)] and bis-(1,3-dibutylbarbituric acid) trimethine oxonol [DiBAC4(3)]
      indicated that DDDC9G induced membrane-depolarization. Furthermore, model
      membrane studies were performed wiith rhodamine-labeled giant unilamellar
      vesicles (GUVs), calcein encapsulating large unilamellar vesicles (ILUVs), and
      FITC-dextran (FD) loaded LUVs. These results demonstrated that the antifungal
      effects of DDDC9G upon the fungal plasma membrane were through the formation of
      pores with the radii between 0.74 nm and 1.4 nm. Finally, in three dimensional
      (3D) flow cytometric contour plots, a reduced cell size was observed as a result
      of osmolarity changes from DDDC9G-induced structural and functional membrane
      damages.Therefore, the present study suggests that DDDC9G exerts its antifungal
      effect by damaging the membrane through pore formation in the fungal plasma
      membrane.

PMID- 22406554
TI  - K+ channels regulate ENaC expression via changes in promoter activity and control
      fluid clearance in alveolar epithelial cells.
AB  - Active Na+ absorption by alveolar ENaC is the main driving force of liquid
      clearance at birth and lung edema resorption in adulthood. We have demonstrated
      previously that long-term modulation of KvLQT1 and KATP K+ channel activities
      exerts sustained control in Na+ transport through the regulation of ENaC
      expression in primary alveolar type II (ATII) cells. The goal of the present
      study was: 1) to investigate the role of the alpha-ENaC promoter, transfected in
      the A549 alveolar cell line, in the regulation of ENaC expression by K+ channels,
      and 2) to determine the physiological impact of K+ channels and ENaC modulation
      on fluid clearance in ATII cells. KvLQT1 and KATP channels were first identified
      in A549 cells by PCR and Western blotting. We showed, for the first time, that
      KvLQT1 activation by R-L3 (applied for 24 h) increased alpha-ENaC expression,
      similarly to KATP activation by pinacidil. Conversely, pharmacological KvLQT1 and
      KATP inhibition or silencing with siRNAs down-regulated alpha-ENaC expression.
      Furthermore, K+ channel blockers significantly decreased alpha-ENaC promoter
      activity. Our results indicated that this decrease in promoter activity could be
      mediated, at least in part, by the repressor activity of ERK1/2. Conversely,
      KvLQT1 and KATP activation dose-dependently enhanced alpha-ENaC promoter
      activity. Finally, we noted a physiological impact of changes in K+ channel
      functions on ERK activity, alpha-, beta-, gamma-ENaC subunit expression and fluid
      absorption through polarized ATII cells. In summary, our results disclose that K+
      channels regulate alpha-ENaC expression by controlling its promoter activity and
      thus affect the alveolar function of fluid clearance.

PMID- 22406555
TI  - MRI-based morphological modeling, synthesis and characterization of cardiac
      tissue-mimicking materials.
AB  - This study uses standard synthetic methodologies to produce tissue-mimicking
      materials that match the morphology and emulate the in vivo murine and human
      cardiac mechanical and imaging characteristics, with dynamic mechanical analysis,
      atomic force microscopy (AFM), scanning electron microscopy (SEM) and magnetic
      resonance imaging. In accordance with such aims, poly(glycerol sebacate) (PGS)
      elastomeric materials were synthesized (at two different glycerol (G)-sebacic (S)
      acid molar ratios; the first was synthesized using a G:S molar ratio of 2:2,
      while the second from a 2:5 G:S molar ratio, resulting in PGS2:2 and PGS2:5
      elastomers, respectively). Unlike the synthesized PGS2:2 elastomers, the PGS2:5
      materials were characterized by an overall mechanical instability in their
      loading behavior under the three successive loading conditions tested. An
      oscillatory response in the mechanical properties of the synthesized elastomers
      was observed throughout the loading cycles, with measured increased storage
      modulus values at the first loading cycle, stabilizing to lower values at
      subsequent cycles. These elastomers were characterized at 4  degrees C and were
      found to have storage modulus values of 850 and 1430 kPa at the third loading
      cycle, respectively, in agreement with previously reported values of the rat and
      human myocardium. SEM of surface topology indicated minor degradation of
      synthesized materials at 10 and 20 d post-immersion in the PBS buffer solution,
      with a noted cluster formation on the PGS2:5 elastomers. AFM nanoindentation
      experiments were also conducted for the measurement of the Young modulus of the
      sample surface (no bulk contribution). Correspondingly, the PGS2:2 elastomer
      indicated significantly decreased surface Young's modulus values 20 d post-PBS
      immersion, compared to dry conditions (Young's modulus = 1160 +/- 290 kPa (dry)
      and 200 +/- 120 kPa (20 d)). In addition to the two-dimensional (2D) elastomers,
      an integrative platform for accurate construction of three-dimensional tissue
      mimicking models of cardiac anatomy from 2D MR images using rapid prototyping
      manufacturing processes was developed. For synthesized elastomers, doping
      strategies with two different concentrations of the MRI contrast agent Dotarem
      allowed independent and concurrent control of the imaging characteristics
      (contrast and relaxivity) during the synthetic process for increased contrast
      agent absorption, with tremendous potential for non-destructive in vivo use and
      applications to cardiovascular and cerebrovascular diseases.

PMID- 22406556
TI  - A task-dependent effect of memory and hand-target on proprioceptive localization.
AB  - We examine whether the task goal affects the accuracy and precision with which
      participants can localize an unseen hand. Proprioceptive localization was
      measured using three different tasks: two goal-directed movement tasks (reaching
      to and reproducing final hand-target location) and a perceptual estimation task
      in which participants judged the location of the hand-target relative to visual
      references. We also assessed whether proprioceptive localization in these
      different tasks is affected by localization from memory, the hand-target being
      localized (left or right) or the movement path of the proprioceptive target (9
      paths, derived from combinations of starting and final hand-target positions). We
      found that participants were less precise when reaching from memory, but not when
      reproducing or estimating remembered final hand-target location. Participants
      also misperceived the felt location of their hands, judging their left hand to be
      more leftward and their right hand to be more rightward when reaching to and when
      estimating final hand-target location, but not when reproducing hand-target
      location. The movement path of the proprioceptive target did not affect
      localization, regardless of the task goal. Overall, localization seems poorer
      when proprioception is used to guide a reach with the opposite hand, particularly
      from memory, and best when merely reproducing the proprioceptive target site.
      This may have an important application in neuro-rehabilitation, whereby one task
      may better establish or re-establish important or failing sensory connections.

PMID- 22406558
TI  - Circulating cell-free DNA is associated with mortality and inflammatory markers
      in nonagenarians: the Vitality 90+ Study.
AB  - Aging is characteristically accompanied by a low-grade inflammatory state and
      increased cellular death. In this study, we analyzed the associations between the
      plasma cell-free DNA (cf-DNA) level and immunoinflammatory factors and 4-year
      mortality. The distribution of qualitative cf-DNA patterns in relation to the
      total cf-DNA concentration and the antinuclear antibody (ANA) serostatus was also
      evaluated. The study population consisted of n=258 nonagenarians who were
      participants in the Vitality 90+ Study. Cf-DNA levels were positively correlated
      with the C-reactive protein (CRP) level, the interleukin-1 receptor antagonist
      (IL-1ra) level, the serum amyloid A (SAA) level and the indoleamine 2,3
      dioxygenase enzyme activity (IDO), weight and chair-stand test time and inversely
      correlated with the HDL cholesterol level. The total cf-DNA concentration also
      remained as an independent predictor of 4-year all-cause mortality. A
      predominance of low-molecular-weight cf-DNA was observed in ANA-seropositive
      subjects but this cf-DNA pattern was not associated with mortality. The cf-DNA
      concentration could thus represent a novel biomarker for systemic inflammation
      and mortality in the elderly.

PMID- 22406557
TI  - Human longevity and variation in GH/IGF-1/insulin signaling, DNA damage signaling
      and repair and pro/antioxidant pathway genes: cross sectional and longitudinal
      studies.
AB  - Here we explore association with human longevity of common genetic variation in
      three major candidate pathways: GH/IGF-1/insulin signaling, DNA damage signaling
      and repair and pro/antioxidants by investigating 1273 tagging SNPs in 148 genes
      composing these pathways. In a case-control study of 1089 oldest-old (age 92-93)
      and 736 middle-aged Danes we found 1 pro/antioxidant SNP (rs1002149 (GSR)), 5
      GH/IGF-1/INS SNPs (rs1207362 (KL), rs2267723 (GHRHR), rs3842755 (INS), rs572169
      (GHSR), rs9456497 (IGF2R)) and 5 DNA repair SNPs (rs11571461 (RAD52), rs13251813
      (WRN), rs1805329 (RAD23B), rs2953983 (POLB), rs3211994 (NTLH1)) to be associated
      with longevity after correction for multiple testing. In a longitudinal study
      with 11 years of follow-up on survival in the oldest-old Danes we found 2
      pro/antioxidant SNPs (rs10047589 (TNXRD1), rs207444 (XDH)), 1 GH/IGF-1/INS SNP
      (rs26802 (GHRL)) and 3 DNA repair SNPs (rs13320360 (MLH1), rs2509049 (H2AFX) and
      rs705649 (XRCC5)) to be associated with mortality in late life after correction
      for multiple testing. When examining the 11 SNPs from the case-control study in
      the longitudinal data, rs3842755 (INS), rs13251813 (WRN) and rs3211994 (NTHL1)
      demonstrated the same directions of effect (p<0.05), while rs9456497 (IGF2R) and
      rs1157146 (RAD52) showed non-significant tendencies, indicative of effects also
      in late life survival. In addition, rs207444 (XDH) presented the same direction
      of effect when inspecting the 6 SNPs from the longitudinal study in the case
      control data, hence, suggesting an effect also in survival from middle age to old
      age. No formal replications were observed when investigating the 11 SNPs from the
      case-control study in 1613 oldest-old (age 95-110) and 1104 middle-aged Germans,
      although rs11571461 (RAD52) did show a supportive non-significant tendency
      (OR=1.162, 95% CI=0.927-1.457). The same was true for rs10047589 (TNXRD1)
      (HR=0.758, 95%CI=0.543-1.058) when examining the 6 SNPs from the longitudinal
      study in a Dutch longitudinal cohort of oldest-old (age 85+, N=563). In
      conclusion, the present candidate gene based association study, the largest to
      date applying a pathway approach, not only points to potential new longevity
      loci, but also underlines the difficulties of replicating association findings in
      independent study populations and thus the difficulties in identifying universal
      longevity polymorphisms.

PMID- 22406559
TI  - Fragrance material review on 1,1-dimethyl-2-phenylethyl propionate.
AB  - A toxicologic and dermatologic review of 1,1-dimethyl-2-phenylethyl propionate
      when used as a fragrance ingredient is presented. 1,1-Dimethyl-2-phenylethyl
      propionate is a member of the fragrance structural group Aryl Alkyl Alcohol
      Simple Acid Esters (AAASAE). The AAASAE fragrance ingredients are prepared by
      reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4
      carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and
      carbonate esters. This review contains a detailed summary of all available
      toxicology and dermatology papers that are related to this individual fragrance
      ingredient and is not intended as a stand-alone document. Available data for 1,1
      dimethyl-2-phenylethyl propionate were evaluated, then summarized, and includes:
      physical properties; acute toxicity; skin irritation; and skin sensitization
      data. A safety assessment of the entire AAASAE will be published simultaneously
      with this document. Please refer to Belsito et al. (submitted for publication)
      for an overall assessment of the safe use of this material and all AAASAE in
      fragrances.

PMID- 22406560
TI  - Fragrance material review on p-isopropylbenzyl acetate.
AB  - A toxicologic and dermatologic review of p-isopropylbenzyl acetate when used as a
      fragrance ingredient is presented. p-Isopropylbenzyl acetate is a member of the
      fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The
      AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with
      a simple carboxylic acid (a chain of 1 to 4 carbons) to generate formate,
      acetate, propionate, butyrate, isobutyrate and carbonate esters. This review
      contains a detailed summary of all available toxicology and dermatology papers
      that are related to this individual fragrance ingredient and is not intended as a
      stand-alone document. Available data for p-isopropylbenzyl acetate were
      evaluated, then summarized, and includes: physical properties, acute toxicity,
      skin irritation, and skin sensitization data. A safety assessment of the entire
      AAASAE will be published simultaneously with this document. Please refer to
      Belsito et al. (2012) for an overall assessment of the safe use of this material
      and all AAASAE in fragrances.

PMID- 22406561
TI  - Fragrance material review on benzyl 2-hydroxypropionate.
AB  - A toxicologic and dermatologic review of benzyl 2-hydroxypropionate when used as
      a fragrance ingredient is presented. Benzyl 2-hydroxypropionate is a member of
      the fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE).
      The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol
      with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate,
      acetate, propionate, butyrate, isobutyrate and carbonate esters. This review
      contains a detailed summary of all available toxicology and dermatology papers
      that are related to this individual fragrance ingredient and is not intended as a
      stand-alone document. Available data for benzyl 2-hydroxypropionate were
      evaluated, then summarized, and includes: physical properties and acute toxicity
      data. A safety assessment of the entire AAASAE will be published simultaneously
      with this document. Please refer to Belsito et al. (2012) for an overall
      assessment of the safe use of this material and all AAASAE in fragrances.

PMID- 22406562
TI  - Fragrance material review on 1,3-dimethyl-3-phenylbutyl acetate.
AB  - A toxicologic and dermatologic review of 1,3-dimethyl-3-phenylbutyl acetate when
      used as a fragrance ingredient is presented. 1,3-Dimethyl-3-phenylbutyl acetate
      is a member of the fragrance structural group Aryl Alkyl Alcohol Simple Acid
      Esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an
      aryl alkyl alcohol with a simple carboxylic acid (a chain of 1 to 4 carbons) to
      generate formate, acetate, propionate, butyrate, isobutyrate and carbonate
      esters. This review contains a detailed summary of all available toxicology and
      dermatology papers that are related to this individual fragrance ingredient and
      is not intended as a stand-alone document. Available data for 1,3-dimethyl-3
      phenylbutyl acetate were evaluated, then summarized, and includes: physical
      properties, acute toxicity, skin irritation, mucous membrane (eye) irritation,
      skin sensitization, elicitation, phototoxicity, and photoallergy data. A safety
      assessment of the entire AAASAE will be published simultaneously with this
      document. Please refer to Belsito et al. (2012) for an overall assessment of the
      safe use of this material and all AAASAE in fragrances.

PMID- 22406563
TI  - Fragrance material review on phenethyl isobutyrate.
AB  - A toxicologic and dermatologic review of phenethyl isobutyrate when used as a
      fragrance ingredient is presented. Phenethyl isobutyrate is a member of the
      fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The
      AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with
      a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate, and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for phenethyl isobutyrate were evaluated, then
      summarized, and includes: physical properties, acute toxicity, skin irritation,
      mucous membrane (eye) irritation, skin sensitization, and genotoxicity data. A
      safety assessment of the entire AAASAE will be published simultaneously with this
      document. Please refer to Belsito et al. (2012) for an overall assessment of the
      safe use of this material and all AAASAE in fragrances.

PMID- 22406564
TI  - Fragrance material review on (4-methoxyphenyl)methyl isobutyrate.
AB  - A toxicologic and dermatologic review of (4-methoxyphenyl)methyl isobutyrate when
      used as a fragrance ingredient is presented. (4-Methoxyphenyl)methyl isobutyrate
      is a member of the fragrance structural group Aryl Alkyl Alcohol Simple Acid
      Esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an
      aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to
      generate formate, acetate, propionate, butyrate, isobutyrate and carbonate
      esters. This review contains a detailed summary of all available toxicology and
      dermatology papers that are related to (4-methoxyphenyl)methyl isobutyrate and is
      not intended as a stand-alone document. Available data were evaluated, then
      summarized, and includes physical properties data. A safety assessment of the
      entire AAASAE will be published simultaneously with this document. Please refer
      to Belsito et al. (2012) for an overall assessment of the safe use of this
      material and all AAASAE in fragrances.

PMID- 22406565
TI  - Fragrance material review on phenethyl propionate.
AB  - A toxicologic and dermatologic review of phenethyl propionate when used as a
      fragrance ingredient is presented. Phenethyl propionate is a member of the
      fragrance structural group aryl alkyl alcohol simple acid esters (AAASAE). The
      AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with
      a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for phenethyl propionate were evaluated, then
      summarized, and includes: physical properties, acute toxicity, skin irritation,
      mucous membrane (eye) irritation, skin sensitization, and elicitation data. A
      safety assessment of the entire AAASAE will be published simultaneously with this
      document. Please refer to Belsito et al. (2012) for an overall assessment of the
      safe use of this material and all AAASAE in fragrances.

PMID- 22406566
TI  - Fragrance material review on 1,1-dimethyl-2-phenylethyl isobutyrate.
AB  - A toxicologic and dermatologic review of 1,1-dimethyl-2-phenylethyl isobutyrate
      when used as a fragrance ingredient is presented. 1,1-Dimethyl-2-phenylethyl
      isobutyrate is a member of the fragrance structural group Aryl Alkyl Alcohol
      Simple Acid Esters (AAASAE). The AAASAE fragrance ingredients are prepared by
      reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4
      carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and
      carbonate esters. This review contains a detailed summary of all available
      toxicology and dermatology papers that are related to this individual fragrance
      ingredient and is not intended as a stand-alone document. Available data for 1,1
      dimethyl-2-phenylethyl isobutyrate were evaluated, then summarized, and includes
      physical properties data. A safety assessment of the entire AAASAE will be
      published simultaneously with this document. Please refer to Belsito et al., 2012
      for an overall assessment of the safe use of this material and all AAASAE in
      fragrances.

PMID- 22406567
TI  - Fragrance material review on benzyl butyrate.
AB  - A toxicologic and dermatologic review of benzyl butyrate when used as a fragrance
      ingredient is presented. Benzyl butyrate is a member of the fragrance structural
      group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The AAASAE fragrance
      ingredients are prepared by reacting an aryl alkyl alcohol with a simple
      carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for benzyl butyrate were evaluated, then
      summarized, and includes: physical properties, acute toxicity, skin irritation,
      skin sensitization, toxicokinetics, and repeated dose data. A safety assessment
      of the entire AAASAE will be published simultaneously with this document. Please
      refer to Belsito et al. (2012) for an overall assessment of the safe use of this
      material and all AAASAE in fragrances.

PMID- 22406568
TI  - Fragrance material review on 1,3-benzodioxole-5-propanol, alpha-methyl-, 5
      acetate.
AB  - A toxicologic and dermatologic review of 1,3-benzodioxole-5-propanol, alpha
      methyl-, 5-acetate when used as a fragrance ingredient is presented. 1,3
      Benzodioxole-5-propanol, alpha-methyl-, 5-acetate is a member of the fragrance
      structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The AAASAE
      fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a
      simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for 1,3-benzodioxole-5-propanol, alpha-methyl-, 5
      acetate were evaluated, then summarized, and includes physical properties. A
      safety assessment of the entire AAASAE will be published simultaneously with this
      document. Please refer to Belsito et al. (2012) for an overall assessment of the
      safe use of this material and all AAASAE in fragrances.

PMID- 22406569
TI  - Fragrance material review on phenethyl formate.
AB  - A toxicologic and dermatologic review of phenethyl formate when used as a
      fragrance ingredient is presented. Phenethyl formate is a member of the fragrance
      structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The AAASAE
      fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a
      simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for phenethyl formate were evaluated, then
      summarized, and includes: physical properties, acute toxicity, skin irritation,
      skin sensitization, and genotoxicity data. A safety assessment of the entire
      AAASAE will be published simultaneously with this document. Please refer to
      Belsito et al. (2012) for an overall assessment of the safe use of this material
      and all AAASAE in fragrances.

PMID- 22406570
TI  - Fragrance material review on alpha-methylbenzyl isobutyrate.
AB  - A toxicologic and dermatologic review of alpha-methylbenzyl isobutyrate when used
      as a fragrance ingredient is presented. alpha-Methylbenzyl isobutyrate is a
      member of the fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters
      (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl
      alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate
      formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This
      review contains a detailed summary of all available toxicology and dermatology
      papers that are related to this individual fragrance ingredient and is not
      intended as a stand-alone document. Available data for alpha-methylbenzyl
      isobutyrate were evaluated, then summarized, and includes physical properties
      data. A safety assessment of the entire AAASAE will be published simultaneously
      with this document. Please refer to Belsito et al. (2012) for an overall
      assessment of the safe use of this material and all AAASAE in fragrances.

PMID- 22406571
TI  - Fragrance material review on phenethyl butyrate.
AB  - A toxicologic and dermatologic review of phenethyl butyrate when used as a
      fragrance ingredient is presented. Phenethyl butyrate is a member of the
      fragrance structural group aryl alkyl alcohol simple acid esters (AAASAE). The
      AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with
      a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for phenethyl butyrate were evaluated, then
      summarized, and includes: physical properties, acute toxicity, skin irritation,
      and skin sensitization data. A safety assessment of the entire AAASAE will be
      published simultaneously with this document. Please refer to Belsito et al.
      (2012) for an overall assessment of the safe use of this material and all AAASAE
      in fragrances.

PMID- 22406572
TI  - Fragrance material review on alpha-methylbenzyl propionate.
AB  - A toxicologic and dermatologic review of alpha-methylbenzyl propionate when used
      as a fragrance ingredient is presented. alpha-Methylbenzyl propionate is a member
      of the fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE).
      The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol
      with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate,
      acetate, propionate, butyrate, isobutyrate, and carbonate esters. This review
      contains a detailed summary of all available toxicology and dermatology papers
      that are related to this individual fragrance ingredient and is not intended as a
      stand-alone document. Available data for alpha-methylbenzyl propionate were
      evaluated, then summarized, and includes: physical properties, acute toxicity,
      skin irritation, skin sensitization data. A safety assessment of the entire
      AAASAE will be published simultaneously with this document. Please refer to
      Belsito et al. (2012) for an overall assessment of the safe use of this material
      and all AAASAE in fragrances.

PMID- 22406573
TI  - Fragrance material review on 1,1-dimethyl-2-phenylethyl formate.
AB  - A toxicologic and dermatologic review of 1,1-dimethyl-2-phenylethyl formate when
      used as a fragrance ingredient is presented. 1,1-Dimethyl-2-phenylethyl formate
      is a member of the fragrance structural group Aryl Alkyl Alcohol Simple Acid
      Esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an
      aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to
      generate formate, acetate, propionate, butyrate, isobutyrate and carbonate
      esters. This review contains a detailed summary of all available toxicology and
      dermatology papers that are related to this individual fragrance ingredient and
      is not intended as a stand-alone document. Available data for 1,1-dimethyl-2
      phenylethyl formate were evaluated, then summarized, and includes: physical
      properties; acute toxicity; skin irritation; mucous membrane (eye) irritation;
      skin sensitization; and genotoxicity data. A safety assessment of the entire
      AAASAE will be published simultaneously with this document. Please refer to
      Belsito et al., 2012 for an overall assessment of the safe use of this material
      and all AAASAE in fragrances.

PMID- 22406574
TI  - Fragrance material review on 1-phenyl-3-methyl-3-pentyl acetate.
AB  - A toxicologic and dermatologic review of 1-phenyl-3-methyl-3-pentyl acetate when
      used as a fragrance ingredient is presented. 1-Phenyl-3-methyl-3-pentyl acetate
      is a member of the fragrance structural group Aryl Alkyl Alcohol Simple Acid
      Esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an
      aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to
      generate formate, acetate, propionate, butyrate, isobutyrate and carbonate
      esters. This review contains a detailed summary of all available toxicology and
      dermatology papers that are related to this individual fragrance ingredient and
      is not intended as a stand-alone document. Available data for 1-phenyl-3-methyl-3
      pentyl acetate were evaluated, then summarized, and includes physical properties,
      acute toxicity, skin irritation, and skin sensitization data. A safety assessment
      of the entire AAASAE will be published simultaneously with this document. Please
      refer to Belsito et al. (2012) for an overall assessment of the safe use of this
      material and all AAASAE in fragrances.

PMID- 22406575
TI  - Fragrance material review on 1,2-ethanediol, 1-phenyl-, 1,2-diacetate.
AB  - A toxicologic and dermatologic review of 1,2-ethanediol, 1-phenyl-, 1,2-diacetate
      when used as a fragrance ingredient is presented. 1,2-Ethanediol, 1-phenyl-, 1,2
      diacetate is a member of the fragrance structural group Aryl Alkyl Alcohol Simple
      Acid Esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting
      an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to
      generate formate, acetate, propionate, butyrate, isobutyrate and carbonate
      esters. This review contains a detailed summary of all available toxicology and
      dermatology papers that are related to this individual fragrance ingredient and
      is not intended as a stand-alone document. Available data for 1,2-ethanediol, 1
      phenyl-, 1,2-diacetate were evaluated, then summarized, and includes physical
      properties data. A safety assessment of the entire AAASAE will be published
      simultaneously with this document. Please refer to Belsito et al. (2012) for an
      overall assessment of the safe use of this material and all AAASAE fragrances.

PMID- 22406576
TI  - Fragrance material review on alpha-methylbenzyl acetate.
AB  - A toxicologic and dermatologic review of alpha-methylbenzyl acetate when used as
      a fragrance ingredient is presented. alpha-Methylbenzyl acetate is a member of
      the fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE).
      The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol
      with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate,
      acetate, propionate, butyrate, isobutyrate and carbonate esters. This review
      contains a detailed summary of all available toxicology and dermatology papers
      that are related to this individual fragrance ingredient and is not intended as a
      stand-alone document. Available data for alpha-methylbenzyl acetate were
      evaluated, then summarized, and includes: physical properties, acute toxicity,
      skin irritation, mucous membrane (eye) irritation, skin sensitization,
      elicitation, and repeated dose data. A safety assessment of the entire AAASAE
      will be published simultaneously with this document. Please refer to Belsito et
      al. (2012) for an overall assessment of the safe use of this material and all
      AAASAE in fragrances.

PMID- 22406577
TI  - Fragrance material review on anisyl propionate.
AB  - A toxicologic and dermatologic review of anisyl propionate when used as a
      fragrance ingredient is presented. Anisyl propionate is a member of the fragrance
      structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The AAASAE
      fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a
      simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for anisyl propionate were evaluated, then
      summarized, and includes: physical properties, acute toxicity, skin irritation,
      and skin sensitization data. A safety assessment of the entire AAASAE will be
      published simultaneously with this document. Please refer to Belsito et al., 2012
      for an overall assessment of the safe use of this material and all AAASAE in
      fragrances.

PMID- 22406578
TI  - Fragrance material review on benzyl formate.
AB  - A toxicologic and dermatologic review of benzyl formate when used as a fragrance
      ingredient is presented. Benzyl formate is a member of the fragrance structural
      group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The AAASAE fragrance
      ingredients are prepared by reacting an aryl alkyl alcohol with a simple
      carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for benzyl formate were evaluated, then
      summarized, and includes physical: properties, acute toxicity, skin irritation,
      mucous membrane (eye) irritation, skin sensitization, and genotoxicity data. A
      safety assessment of the entire AAASAE will be published simultaneously with this
      document. Please refer to Belsito et al., 2012 for an overall assessment of the
      safe use of this material and all AAASAE in fragrances.

PMID- 22406579
TI  - Impact of thermal processing and the Maillard reaction on the basophil activation
      of hazelnut allergic patients.
AB  - Food allergy, an abnormal immunological response due to sensitization to a food
      component, has become an important health problem, especially in industrialized
      countries. The aim of this study was to investigate the impact of thermal
      processing and glycation on the basophil activation by hazelnut proteins using a
      basophil activation test. Patients with systemic allergic reactions (SR; n=6) to
      hazelnut as well as patients with an isolated oral allergy syndrome (OAS; n=4)
      were investigated. Thermal processing of hazelnut proteins either in the presence
      or absence of wheat proteins did not result in major changes in the stimulatory
      activity of the basophils for patients with SR or OAS. For the patients with OAS,
      incubation of hazelnut proteins with glucose led to complete depletion of the
      stimulatory activity of the basophils. An increase in stimulatory activity of the
      basophils for two out of six patients with SR was observed. For the other four
      patients slight or complete abolition of the stimulatory activity was observed.
      These results indicate that some patients with SR to hazelnut are at risk when
      exposed to hazelnut proteins, even in processed foods.

PMID- 22406580
TI  - Baby-led weaning and the family diet. A pilot study.
AB  - Baby-led weaning (BLW) is a style of solid food introduction that emphasizes self
      feeding rather than spoon-feeding. The purpose of this cross-sectional study was
      to determine whether parents using BLW change their dietary intake during
      weaning, and if their babies are offered family foods. Participants kept diet
      diaries at baseline and three months later, post-BLW implementation. Wilcoxon
      tests revealed no significant changes in dietary intake during the first three
      months of weaning, however, parents offered their children 57% of the same foods
      they were consuming. Results suggest that BLW does not lead to dietary changes
      among parents during the weaning process.

PMID- 22406581
TI  - Pancreatic neoplasm in 2012: an update. Tissue is an issue!

PMID- 22406582
TI  - Revising you the staging for pancreatic cancer in 2012.

PMID- 22406583
TI  - Early detection of pancreatic cancer.
AB  - Despite treatment advances pancreatic cancer remains one of the most lethal
      malignancies. It is expected that early detection and screening of high risk
      patient population may have the most significant impact on altering overall
      survival in this disease. Serologic biomarkers may be the most useful in early
      detection and histology-based markers may have the most significant role in
      differentiating benign, pre-malignant and malignant lesions. Here we review
      several serum and tissue-based biomarkers and summarize new data presented at the
      2012 ASCO Gastrointestinal Cancers Symposium (Abstracts #151, #164, #188) on the
      potential role of PAM4 in pancreatic cancer screening and diagnosis.

PMID- 22406584
TI  - Intraductal papillary mucinous neoplasms of the pancreas: clinical surveillance
      and malignant progression, multifocality and implications of a field-defect.
AB  - Intraductal papillary mucinous neoplasms (IPMNs) are a heterogeneous group of
      mucin producing cystic tumors that involve the main pancreatic duct and/or branch
      ducts and may be associated with invasive carcinoma. Predicting the risk of
      malignant transformation of an IPMN lesion can be challenging. The Sendai
      criteria, based in large part on radiographic imaging features, help guide
      surgical intervention based on the stratification of cysts into high and low risk
      lesions for malignancy. Invasive carcinoma may develop in the index IPMN lesion
      or in a separate site within the pancreas, supporting the concept of a field
      defect in IPMN tumorigenesis. This stresses the importance of evaluation of the
      entire pancreas upon diagnosis of IPMN and continued surveillance of the residual
      pancreas following resection. Herein, the authors summarize the data presented at
      the 2012 ASCO Gastrointestinal Cancers Symposium regarding prevalence and site of
      invasive carcinoma detected in patients undergoing surveillance for IPMN
      (Abstract #152).

PMID- 22406585
TI  - Adjuvant strategies for resectable pancreatic cancer: have we made progress?
AB  - Substantial controversy remains regarding the optimal adjuvant treatment for
      patients with resectable pancreatic adenocarcinoma. Despite improvements in
      radiation techniques, systemic therapies, and incorporation of targeted agents,
      the 5-year survival rates for early stage patients remains less than 25% and the
      optimal adjuvant treatment approach remains unclear. Here we summarize the data
      presented at the 2012 American Society of Clinical Oncology (ASCO)
      Gastrointestinal Cancers Symposium regarding controversial issues surrounding the
      role, timing, and selection of patients for adjuvant chemoradiation strategies
      following curative resection for pancreatic adenocarcinoma. (Abstracts #301,
      #333, and #206).

PMID- 22406586
TI  - An update on surgical staging of patients with pancreatic cancer.
AB  - Accurate staging of pancreatic adenocarcinoma is a crucial step in determining
      the appropriate therapeutic approach to pancreatic cancer and to maximizing life
      expectancy. Despite the availability of high-quality abdominal imaging, the use
      of multi-modality imaging and of diagnostic laparoscopy, a portion of surgically
      explored patients fail to undergo resection secondary to metastatic disease. This
      review is an update from the 2012 American Society of Clinical Oncology (ASCO)
      Gastrointestinal Cancers Symposium of new developments in the staging of
      localized pancreatic adenocarcinoma. (Abstracts #168, #177, and #212).

PMID- 22406587
TI  - Management of borderline resectable pancreatic adenocarcinoma.
AB  - Pancreatic adenocarcinoma is the fourth most common cause of cancer-related death
      among U.S. men and women. Despite much effort in translational research,
      pancreatic adenocarcinoma remains a challenging disease with an overall 5-year
      survival rate less than 5%. To date, the only potentially curative treatment for
      managing pancreatic adenocarcinoma is surgical resection. However, more than 80%
      of patients are deemed either unresectable or metastatic upon diagnosis. For
      borderline resectable disease, although there is no high-level evidence
      supporting its use, an initial approach involving neoadjuvant therapy is
      preferred, as opposed to immediate surgery. In this year's ASCO Gastrointestinal
      Cancers Symposium, several studies were presented with approaches towards
      treating borderline resectable pancreatic adenocarcinoma. Retrospective studies
      (Abstract #280, #304, #327) were presented and showed that neoadjuvant
      chemoradiation were associated with higher rates of negative margin resection and
      better survival. The tolerability of accelerated fraction radiotherapy with
      concomitant capecitabine was demonstrated in a phase I study (Abstract #329).
      More effective therapeutic approaches and prospective studies are needed for this
      devastating illness. This highlight article will focus on the management of
      borderline resectable pancreatic adenocarcinoma.

PMID- 22406588
TI  - Resectable pancreatic cancer: is surgery the best first step?
AB  - Controversy exist regarding the potential benefit of the neoadjuvant approach to
      pancreatic cancer as limited retrospective data exists comparing pre- with post
      operative chemoradiation. The optimal treatment approach remains unclear as we
      await prospective randomized clinical trials evaluating the hypothesized benefit
      of the neoadjuvant therapy for resectable pancreatic cancer and as there has been
      no proven survival benefit to date. Here we summarize the data presented at the
      2012 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers
      Symposium providing additional insight into the potential of neoadjuvant therapy
      in the treatment of pancreatic cancer. (Abstracts #156, #162, #168 and #177).

PMID- 22406589
TI  - Locally advanced pancreatic adenocarcinoma: update and progress.
AB  - Pancreatic cancer, the 4th leading cause of cancer death in the U.S., remains a
      challenging disease for the oncology community. Less than 20% of all cases are
      potentially cured by surgical resection, while the large majority of cases are
      deemed either unresectable or metastatic upon diagnosis. Advances in treating
      locally advanced pancreatic cancer have been few and modest. In this year's
      American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium,
      three abstracts (#252, #254, #313) were presented with novel approaches towards
      treating locally advanced pancreatic cancer. Surgery for recurrent disease, a
      promising new chemoradiation regimen, and the application of an exciting multi
      agent regimen (FOLFIRINOX: oxaliplatin, irinotecan, leucovorin, 5-fluorouracil)
      in a non-clinical trial setting, highlight the novel approaches focused on the
      management of this difficult disease.

PMID- 22406590
TI  - First-line treatment of metastatic pancreatic cancer.
AB  - Metastatic pancreatic cancer is an aggressive malignancy that is difficult to
      treat. Gemcitabine monotherapy has been used first line and many contemporary
      treatment approaches have focused on gemcitabine plus experimental agents. The
      2012 ASCO Gastrointestinal Cancers Symposium Abstract #213 is a study of
      gemcitabine with IPI-926, a novel hedgehog pathway inhibitor. Abstract #227 is a
      study of gemcitabine with 90Y-hPAM4 radioimmunotherapy with yttrium labeled anti
      mucin humanized antibody. Abstract #296 is a study of gemcitabine with
      temsirolimus, an mTOR inhibitor. Gemcitabine and erlotinib has shown slight
      advantages to gemcitabine alone. Abstract #253 takes this one step further and
      evaluates gemcitabine and erlotinib with apricoxib, a COX-2 inhibitor. FOLFIRINOX
      has shown superiority to gemcitabine; however, doing so at the cost of
      significantly greater toxicity. Abstract #199, is a study which examines the cost
      effectiveness of first line FOLFIRINOX approaches. Another cost effective study
      is portrayed in Abstract #372, a study evaluating the survival of unresectable
      pancreatic cancer patients treated with gemcitabine and the disease course is
      followed clinically without radiographic follow-up.

PMID- 22406591
TI  - What options are available for refractory pancreatic cancer?
AB  - Currently gemcitabine-based regimens and FOLFIRINOX (5-fluorouracil, leucovorin,
      irinotecan, and oxaliplatin) are widely used standard for first-line treatment of
      patients with advanced pancreatic adenocarcinoma. Refractory patients may receive
      either FOLFOX (5-fluorouracil and oxaliplatin) or gemcitabine based on the first
      line regimen. This review is an update from the 2012 American Society of Clinical
      Oncology (ASCO) Gastrointestinal Cancers Symposium regarding recent developments
      in the treatment of refractory pancreatic cancer, as these were presented in
      Abstracts #248 and #373 of the meeting.

PMID- 22406592
TI  - Novel agents in early phase clinical studies on refractory pancreatic cancer.
AB  - The standard current treatment options in advanced pancreatic cancer have
      demonstrated minimal or modest only efficacy for the majority of patients.
      Unfortunately, the mortality and morbidity remain high crying out for better
      treatments and results. With the exception of erlotinib, which received approval
      by the Food and Drug Administration of the United States in 2005, no other novel
      agents have since been added in our treatment quiver. Therefore, the search for
      novel approaches continuous at the laboratory and clinical level. At the 2012
      American Society of Clinical Oncology Gastrointestinal Symposium, results of some
      interesting early phases clinical studies were presented. First, in Abstract
      #198, toxicity and efficacy results from the phase I/II study of cixutumumab, an
      insulin growth factor-1 receptor (IGF-1R) antibody combined with the standard
      gemcitabine and erlotinib treatment were presented, but the outcomes suggest no
      real clinical benefit. Second, the early safety and clinical data from the novel
      monoclonal antibody (ensituximab) against the mucin epitope NPC-1C in pancreatic
      and colon cancer patients were presented (Abstract #233) and again no particular
      efficacy was observed. Finally, interesting results which definitely deserve
      further exploration were presented in Abstract #211, which tested the combination
      of ipilimumab, an antibody against the cytotoxic T-lymphocyte antigen 4 (CTLA-4),
      with a cell-based vaccine transfected with the granulocyte macrophage colony
      stimulating factor (GM-CSF) gene in advanced refractory pancreatic cancer.
      Though, it seems we have not yet found the culprit and the solution of this
      devastating disease, a small step forward might have been achieved.

PMID- 22406593
TI  - Pancreatic neuroendocrine tumors: entering a new era.
AB  - Neuroendocrine tumors (NETs) describe a heterogeneous group of tumors with a wide
      range of morphologic, functional, and behavioral characteristics. These tumors
      are generally slow growing and behave in an indolent fashion. However, they have
      the potential to spread, primarily to the liver and when they do, they can be
      life threatening and difficult to treat with current modalities. A subset of
      NETs, the pancreatic neuroendocrine tumors (pNET) represent a small percentage of
      all pancreatic tumors (1.3%) but their incidence is rising. Prior to 2011, the
      only approved agent for unresectable pNETs was streptozocin (often used in
      combination with doxorubicin) but the efficacy of this drug was questionable. In
      2011, the landscape of treatment for pNET was changed with the approval of the
      first new agents in 20 years, sunitinib and everolimus, that demonstrated
      improvement in time to progression in patients with progressive pNET. Sunitinib
      is a multikinase inhibitor and everolimus is an inhibitor of the mammalian target
      of rapamycin (mTOR) pathway. These drugs were approved by the Food and Drug
      Administration (FDA) on the basis of separate large randomized placebo-controlled
      trials. Data from these two trials and an additional phase III trial looking at
      everolimus in other neuroendocrine tumors has generated intense interest in this
      challenging disease. At the 2012 American Society of Clinical Oncology (ASCO)
      Gastrointestinal Cancers Symposium, several researchers presented updated data
      regarding the risk stratification, treatment, and outcome for patients with pNET
      in the new era of targeted therapy. Choti et al. (Abstract #187) reviewed
      demographic data from a large set of patients who presented to National
      Comprehensive Cancer Network (NCCN) sites with neuroendocrine tumors. Casciano et
      al. (Abstract #226) and Signorovitch et al. (Abstract #237) presented post
      approval analysis of the relative role of everolimus and sunitinib in the
      treatment of pNET. Alistar et al. (Abstract #166) explored predictive biomarkers
      in pNET, and Yao et al. (Abstract #157) conducted multivariate analysis of
      patients treated with everolimus in the phase III, RADIANT-2 trial which included
      the identification of relevant biomarkers. Hobday et al. (Abstract #260) and
      Bergsland et al. (Abstract #285) reported phase II data from two clinical trials
      looking at novel targeted combinations for the treatment of pNET. Finally the
      role of treatment for poorly differentiated NETs (including pNETs) remains ill
      defined and Yamaguchi et al. (Abstract #274) presented a report reviewing the
      experience at 23 centers in Japan in treating this population. The authors review
      and summarize these abstracts in this article.

PMID- 22406594
TI  - Is there a role of radiotherapy in the management of pancreatic neuroendocrine
      tumors (PNET)?
AB  - Pancreatic neuroendocrine tumors (PNET) represent a heterogeneous group of tumors
      with varying tumor biology and prognosis. Advanced PNETs remain a difficult
      therapeutic challenge because of their high malignant potential and their
      resistance to conventional chemotherapy although there have been recent
      developments with promising results with the use of novel agents for the
      treatment of this disease. Combined modality chemoradiation is not widely used in
      the management of locally advanced pancreatic endocrine tumors. We discuss
      Abstract #335 from 2012 ASCO GI Cancers Symposium and share our experience to
      discuss efficacy and toxicity of concurrent capecitabine or infusional 5
      fluorouracil and radiotherapy in patients with resected, locally advanced and
      metastatic PNET. Prospective studies to investigate the role of radiation and
      chemoradiation are warranted.

PMID- 22406595
TI  - Translational research. New findings and potential future applications in
      pancreatic adenocarcinoma.
AB  - The current achievements in pancreatic cancer diagnosis and treatment are
      disappointing for patients and clinicians alike. Still, in the dawn of 2012, most
      patients are diagnosed at a late stage where cure is not feasible, with the
      majority going to succumb within the same year of diagnosis. Thus, the only hope
      for early and diagnosis and radical treatment is the invention of diagnostic and
      prognostic tests which might predict accurately patients who may develop this
      disease and those who have the most aggressive potential, so clinician adopt the
      appropriate strategy. In this paper we summarize the findings from the three most
      interesting research abstract as presented at the 2012 American Society of
      Clinical Oncology Gastrointestinal Cancers Symposium. In particular, we focus on
      Abstract #160 which shows the diagnostic utility of microRNA serum profiling in
      pancreatic cancer patients, on Abstract #201 which suggests a potential
      prognostic role of transforming growth factor (TGF)-beta pathway in advanced
      pancreatic cancer, and on Abstract #165 which shows that protein S100A4 might be
      a new, potentially useful, predictive biomarker of gemcitabine efficacy.

PMID- 22406596
TI  - BRCA and pancreatic cancer: selection of chemotherapy.
AB  - Germline mutations in BRCA genes are associated with increased risk of pancreatic
      cancer. There are pre clinical data which suggests that DNA cross linking agents
      should be used in pancreatic cancer patients with BRCA mutations. This review is
      an update from the 2012 American Society of Clinical Oncology (ASCO)
      Gastrointestinal Cancers Symposium regarding recent developments in the treatment
      of pancreatic cancer with BRCA mutation. Only one study (Abstracts #217) was
      presented and it is described here.

PMID- 22406597
TI  - Quality of life in patients with pancreatic cancer.
AB  - Pancreatic cancer is a rapidly fatal disease with palliation often serving as the
      main goal of treatment. The end of life is often marked by severe symptoms and
      poor quality of life (QoL). Several studies presented at the 2012 ASCO
      Gastrointestinal Cancers Symposium addressed the importance of symptom
      identification and management for patients with pancreatic cancer: 1) a study
      evaluating the correlation between patient-reported symptoms, disease burden and
      treatment duration in patients with advanced pancreatic cancer undergoing
      gemcitabine-based chemotherapy (Abstract #370); 2) a Japanese study found that
      patients without worsening of pain or sleep symptoms at one month of chemotherapy
      had higher frequency of disease control (Abstract #195); and 3) a study showed
      that fear of cancer recurrence is a substantial problem following resection and
      should be targeted (Abstract #289). The authors summarize the findings and
      discuss the importance of QoL in these patients. The results of these studies may
      facilitate in identifying symptom changes as predictive markers, and improving
      care and QoL for patients with this devastating disease.

PMID- 22406598
TI  - Pancreatic cancer and thromboembolism in the ambulatory community.
AB  - Pancreatic exocrine adenocarcinoma is one of the most common malignancies
      associated with thromboembolism. The authors summarize the two abstracts (#368
      and #273) presented at the 2012 ASCO Gastrointestinal Cancers Symposium which
      were focused on pancreatic thrombosis in ambulatory patients. In addition, they
      discuss the risk of thrombosis associated with malignancy, chemotherapy, and
      erythropoietin stimulating agents and the management and implications thereof.

PMID- 22406599
TI  - Endoscopic management of pancreatic injury due to abdominal trauma.
AB  - CONTEXT: There is limited experience with pancreatic endotherapy in patients with
      pancreatic injury due to trauma. OBJECTIVE: To retrospectively evaluate our
      experience of endoscopic management of pancreatic trauma. PATIENTS: Eleven
      patients (10 males and 1 female; mean age: 21.8+/-11.9 years) with pancreatic
      trauma. INTERVENTION: Endoscopic therapy. Patients with pseudocyst and a
      gastroduodenal bulge were treated with endoscopic transmural drainage.
      Pseudocysts without bulge or patients with external pancreatic fistula were
      treated with transpapillary drainage. RESULTS: Seven patients (6 males, 1 female)
      were treated for symptomatic pseudocyst and 4 patients (all males) were treated
      for persistent external pancreatic fistula. Three patients with external
      pancreatic fistula had partial disruption of pancreatic duct (head: 2 cases;
      tail: 1 case) and were successfully treated with bridging pancreatic stent (2
      cases) or bridging nasopancreatic drain (1 case) with resolution of external
      pancreatic fistula in 4 to 6 weeks. Of seven patients presenting with symptomatic
      pseudocyst (size range: 4-14 cm), two patients were successfully treated with
      cystogastrostomy and there has been no recurrence over a follow up of 20 and 16
      months, respectively. Five patients underwent transpapillary drainage. Three
      patients had partial disruption and two had complete disruption. In the former, a
      bridging nasopancreatic drain was placed in one patient and stent in two
      patients. All three patients had resolution of pseudocyst within 8 weeks and
      there has been no recurrence over a follow-up of 11 to 70 months. In two patients
      with complete disruption, non-bridging stent did not resolve the pseudocysts and
      required surgery. CONCLUSION: Pancreatic injury due to trauma can be effectively
      treated endoscopically.

PMID- 22406600
TI  - Late postpancreatectomy hemorrhage after pancreaticoduodenectomy: is it possible
      to recognize risk factors?
AB  - CONTEXT: Post-pancreatectomy hemorrhage is one of the most common complications
      after pancreaticoduodenectomy. OBJECTIVE: To evaluate the late post
      pancreatectomy hemorrhage rate according to the International Study Group of
      Pancreatic Surgery criteria and to recognize factors related to its onset.
      METHODS: A prospective study of 113 patients who underwent
      pancreaticoduodenectomy was conducted. Late post-pancreatectomy hemorrhage was
      defined according to the criteria of the International Study Group of Pancreatic
      Surgery. Demographic, clinical, surgical and pathological data were considered
      and related to late post-pancreatectomy hemorrhage. RESULTS: Thirty-one (27.4%)
      patients had a post-pancreatectomy hemorrhage. Twenty-five (22.1%) patients
      developed late post-pancreatectomy hemorrhage: 19 (16.8%) grade B, 6 (5.3%) grade
      C. Surgical re-operation was performed in 2 out of the 25 cases with late post
      pancreatectomy hemorrhage (8.0%) grade C associated with postoperative pancreatic
      fistula. At univariate analysis, the only factor significantly related to late
      post-pancreatectomy hemorrhage was postoperative pancreatic fistula (P<0.001).
      Multivariate analysis underlined that the severity of postoperative pancreatic
      fistula (P<0.001) and pancreatic anastomosis (P=0.049) independently increased
      the risk of late hemorrhage. CONCLUSION: In patients undergoing
      pancreaticoduodenectomy, the criteria introduced by International Study Group of
      Pancreatic Surgery to define late postpancreatectomy hemorrhage are related to a
      higher incidence of hemorrhage than previously detected because they considered
      also mild hemorrhage.

PMID- 22406601
TI  - Preoperative serum C-reactive protein levels and post-operative lymph node ratio
      are important predictors of survival after pancreaticoduodenectomy for pancreatic
      ductal adenocarcinoma.
AB  - CONTEXT: There is paucity of data on the prognostic value of pre-operative
      inflammatory response and post-operative lymph node ratio on patient survival
      after pancreatic-head resection for pancreatic ductal adenocarcinoma. OBJECTIVES:
      To evaluate the role of the preoperative inflammatory response and postoperative
      pathology criteria to identify predictive and/or prognostic variables for
      pancreatic ductal adenocarcinoma. DESIGN: All patients who underwent
      pancreaticoduodenectomy for pancreatic ductal adenocarcinoma between 2002 and
      2008 were reviewed retrospectively. The following impacts on patient survival
      were assessed: i) preoperative serum CRP levels, white cell count, neutrophil
      count, neutrophil/lymphocyte ratio, lymphocyte count, platelet/lymphocyte ratio;
      and ii) post-operative pathology criteria including lymph node status and lymph
      node ratio. RESULTS: Fifty-one patients underwent potentially curative resection
      for pancreatic ductal adenocarcinoma during the study period. An elevated
      preoperative CRP level (greater than 3 mg/L) was found to be a significant
      adverse prognostic factor (P=0.015) predicting a poor survival, whereas white
      cell count (P=0.278), neutrophil count (P=0.850), neutrophil/lymphocyte ratio
      (P=0.272), platelet/lymphocyte ratio (P=0.532) and lymphocyte count (P=0.721)
      were not significant prognosticators at univariate analysis. Presence of
      metastatic lymph nodes did not adversely affect survival (P=0.050), however a
      raised lymph node ratio predicted poor survival at univariate analysis (P<0.001).
      The preoperative serum CRP level retained significance at multivariate analysis
      (P=0.011), together with lymph node ratio (P<0.001) and tumour size (greater than
      2 cm; P=0.008). CONCLUSION: A pre-operative elevated serum CRP level and raised
      post-operative lymph node ratio represent significant independent prognostic
      factors that predict poor prognosis in patients undergoing curative resection for
      pancreatic ductal adenocarcinoma. There is potential for future neo-adjuvant and
      adjuvant treatment strategies in pancreatic cancer to be tailored based on
      preoperative and postoperative factors that predict a poor survival.

PMID- 22406602
TI  - Secular trends of fibrocalculous pancreatic diabetes and diabetes secondary to
      alcoholic chronic pancreatitis at a tertiary care diabetes centre in South India.
AB  - CONTEXT: Data on prevalence and trends in diabetes secondary to chronic
      pancreatitis in developing countries is scarce. OBJECTIVE: To compare the secular
      trends in the prevalence of fibrocalculous pancreatic diabetes (FCPD) and
      diabetes secondary to alcoholic chronic pancreatitis (ACP) at a diabetes centre
      in south India. DESIGN: A retrospective analysis was done of all patients
      registered at Dr. Mohan's Diabetes Specialties Centre, Chennai, India between
      January 1991 and December 2010. PATIENTS: A total of 1,079 subjects with diabetes
      secondary to chronic pancreatitis were identified, of whom 47 were excluded
      because of difficulty in classification. MAIN OUTCOME MEASURE: The number of
      patients with FCPD and diabetes secondary to ACP were calculated as a percentage
      of the total number of diabetes patients seen at the centre during five year
      blocks. RESULTS: Of the total of 1,032 cases of diabetes secondary to chronic
      pancreatitis, FCPD comprised 898 (87%) and ACP 134 (13%). The prevalence of FCPD
      decreased from 1.6% during 1991-1995 to 0.2% during 2006-2010 (P<0.001). The
      prevalence of ACP remained constant at 0.1%. The age at diagnosis of FCPD
      increased (P=0.002) while that of ACP decreased (P=0.025) during the study
      period. There was a significant increase in BMI of FCPD P<0.001), but not of ACP
      (P=0.248) patients. CONCLUSIONS: At this centre, FCPD continues to be more common
      than ACP, but there is a decline in its frequency. The age at diagnosis of FCPD
      has increased, while that of ACP has decreased. The decline in FCPD probably
      reflects improved nutrition.

PMID- 22406603
TI  - Transduodenal endosonography-guided biliary drainage and duodenal stenting for
      palliation of malignant obstructive jaundice and duodenal obstruction.
AB  - CONTEXT: Endosonography-guided biliary drainage has been used over the last few
      years as a salvage procedure when endoscopic retrograde cholangiopancreatography
      fails. Malignant gastric outlet obstruction may also be present in these
      patients. We report the results of both procedures during the same session in
      patients with duodenal and biliary obstruction due to malignant disease. METHODS:
      A retrospective review from a prospective collected database. RESULTS: Technical
      success was achieved in all five patients; however, only three patients
      experienced relief of jaundice and gastric outlet obstruction. CONCLUSIONS:
      Endosonography-guided biliary drainage and duodenal stenting in the same session
      is feasible. However, severe complications may limit the procedure. This is a
      challenging procedure and should be done by experts with special attention to
      patient's selection.

PMID- 22406604
TI  - Acute pancreatitis in a patient with vivax malaria.
AB  - CONTEXT: Acute pancreatitis is most commonly linked to gallstone disease or
      alcohol consumption. Occasionally it can follow infectious disease. Malaria,
      especially Plasmodium falciparum infection, has been associated with acute
      pancreatitis. CASE REPORT: We present the case of a 17-year-old male who
      presented with a history of fever, abdominal pain and hypotension and revealing
      acute pancreatitis associated with infection by Plasmodium vivax. CONCLUSION:
      Acute pancreatitis can accompany malaria, including Plasmodium vivax.

PMID- 22406605
TI  - Primary pancreatic choriocarcinoma presenting as pancreatitis.
AB  - CONTEXT: Pancreatic cancers can present with pancreatitis or its complications.
      Pancreatic choriocarcinoma is an extremely rare disease to involve pancreas. CASE
      REPORT: A 27-year-old married woman presented to our facility with abdominal pain
      and fullness of 20-day duration. She was clinically diagnosed as acute
      pancreatitis with pseudocyst as a complication. Serum amylase was elevated with
      CT scan of abdomen showing a cystic lesion involving the pancreas. We approached
      the cyst with endoscopic ultrasonography and cyst fluid was aspirated and
      analyzed. Cyst fluid amylase was elevated and cytology revealed germ cell tumor.
      Serum beta human chorionic gonadotropin was elevated. She had a swelling over the
      jaw which also revealed choriocarcinoma in histopathological examination. Patient
      was started with chemotherapy. CONCLUSION: We report this case of pancreatic
      choriocarcinoma due to its extreme rarity and the diagnostic dilemma it posed.

PMID- 22406606
TI  - Colloid carcinoma of the pancreas: a distinct pancreatic neoplasm with good
      prognosis. Report of a case.
AB  - CONTEXT: Colloid carcinoma is considered a distinct type of pancreatic neoplasia
      with specific histopathological and molecular features, and a better prognosis.
      CASE REPORT: We present the case of a patient with a 15 cm locally invasive
      colloid carcinoma of the pancreas, in which an aggressive surgical approach
      achieved no evidence of disease 24 months after surgery. CONCLUSIONS: If an
      accurate diagnostic approach and surgical resection are performed, the 5-year
      survival rate can reach 60%. Presence of invasive intraductal papillary mucinous
      neoplasm has been reported, and this can affect the prognosis. Adjuvant therapy
      has not demonstrated improvement of survival in surgically-resected patients.

PMID- 22406607
TI  - Rare cause of delayed upper gastrointestinal bleeding after
      pancreaticoduodenectomy.
AB  - CONTEXT: Luminal bleeding after pancreaticoduodenectomy can be present in various
      degrees of acuity in up to 30% of patients. CASE REPORT: In this report, we
      describe a rare and uncommon cause of gastrointestinal bleeding after
      pancreaticoduodenectomy and review of the literature. CONCLUSIONS: Multiple
      biliary procedures with common complications increase the difficulty making the
      correct diagnosis and therefore all possible etiologies of a complication must be
      evaluated.

PMID- 22406608
TI  - VIP and calcitonin-producing pancreatic neuroendocrine tumor with watery
      diarrhea: clinicopathological features and the effect of somatostatin analogue.
AB  - CONTEXT: Pancreatic neuroendocrine tumor (pNET) secretes various peptide
      hormones; however, calcitonin hypersecretion is rare. Its clinicopathological
      significance and treatment is still controversial. CASE REPORT: A 43 year-old
      Japanese man presented severe watery diarrhea and a large mass in the pancreatic
      tail. Blood concentration of VIP was elevated to 649 pg/mL (reference range: 0
      100 pg/mL), and calcitonin to 66,700 pg/mL (reference range: 15-86 pg/mL). There
      was no tumor in other endocrine organs. The resected tumor was composed of 80%
      calcitonin-positive cells and 10% VIP-positive cells. After the operation, the
      levels of VIP and calcitonin were decreased to 44 and 553 pg/mL, respectively,
      and diarrhea was improved. The mRNA of somatostatin receptor (SSTR) subtypes 2, 3
      and 5 in the tumor tissue were increased 22.8, 25.1, and 37.0-fold of those of
      normal pancreas, respectively. At 19 months after the operation, blood calcitonin
      was again raised to 3,980 pg/mL, and metastatic tumors were found in the liver.
      With the treatment of long-acting somatostatin analogue, calcitonin was reduced
      to 803 pg/mL. The patient does not present endocrine symptom, and the size of the
      metastatic tumors appears stable. CONCLUSION: From the world literature to date,
      co-secretion of VIP and calcitonin was documented in only 10 cases of pNET
      including the current case. Although VIP is a primary cause of diarrhea in these
      cases, high level of calcitonin may also influence on the clinical symptoms.
      Somatostatin analogue suppresses the levels of VIP and calcitonin, and the
      control proliferation is also expected when tumor cells express SSTRs.

PMID- 22406609
TI  - Catastrophic arteriovenous thromboembolism as initial manifestation of pancreatic
      cancer.
AB  - CONTEXT: The association between cancer and thrombosis is well-known. Among
      gastrointestinal malignancies, pancreatic cancer has perhaps the strongest
      association with thromboembolic events. However, simultaneous arterial and venous
      thromboses affecting multiple organs at the time of initial diagnosis is rare,
      with an incidence of less than 1%. CASE REPORT: We report herein a case of a 61
      year-old woman who presented with digital ischemia, a non-ST elevation myocardial
      infarction and an ischemic stroke, along with deep vein thromboses and pulmonary
      embolism. She was subsequently diagnosed with metastatic pancreatic cancer.
      DISCUSSION: This report highlights the intriguing association between pancreatic
      cancer biology, tumor metastases, and triggering of venous and arterial
      thromboembolic events. Current evidence points towards early thromboembolic
      phenomena as a harbinger of poor outcome in pancreatic cancer, and studies
      attempting to define the role of prophylactic anticoagulation in these patients
      are ongoing.

PMID- 22406610
TI  - Elevation of pancreatic enzymes in gallbladder bile associated with heterotopic
      pancreas. A case report and review of the literature.
AB  - CONTEXT: This is the first report associating heterotopic pancreas in the
      gallbladder and elevated pancreatic enzymes in bile. CASE REPORT: A 60-year-old
      woman underwent abdominal ultrasonography at a medical check-up, revealing a
      nodular protrusion at the neck of the gallbladder. It seemed likely to be a lymph
      node, but we could not exclude the possibility of gallbladder cancer. In order to
      make a correct diagnosis, laparoscopic cholecystectomy was successfully
      performed. Pathological examination revealed heterotopic pancreatic tissue in the
      gallbladder wall. In addition, we detected elevated levels of amylase and lipase
      in gallbladder bile. CONCLUSIONS: Preoperative diagnosis of heterotopic pancreas
      in the gallbladder is difficult. However, an increase of pancreatic enzymes in
      gallbladder bile may potentially play an important role in the occurrence of
      acalculous cholecystitis and biliary cancer. We need more accumulation of cases
      to know the true significance of this anomaly.

PMID- 22406611
TI  - Total pancreatectomy and islet auto-transplantation as treatment for ampullary
      adenocarcinoma in the setting of pancreatic ductal disruption secondary to acute
      necrotizing pancreatitis. A case report.
AB  - CONTEXT: Ampullary adenocarcinoma is the third most common periampullary
      malignancy. Obstruction of the main pancreatic duct is linked with an increased
      incidence of acute pancreatitis. Acute necrotizing pancreatitis leading to
      pancreatic duct disruption carries significant morbidity. When these conditions
      occur in combination, the treatment can be drastically limited as
      pancreaticoduodenectomy is not a viable option in the setting of friable ductal
      tissue, which precludes pancreatic ductal anastomosis and can lead to the
      complications of leak or stricture. CASE REPORT: Our patient is a 72-year-old
      woman who developed pancreatic ductal disruption and splenic vein thrombosis as a
      result of acute necrotizing pancreatitis. Concurrently, she was found to have an
      ampullary adenoma with high-grade dysplasia. Her treatment options were limited,
      as she was neither a candidate for pancreaticoduodenectomy given the ductal
      disruption nor total pancreatectomy, which would render her a brittle diabetic.
      She was successfully treated with total pancreatectomy and islet auto
      transplantation thereby resecting her ampullary lesion while both avoiding a
      pancreatic anastomosis and preserving pancreatic endocrine beta-cell function.
      CONCLUSION: We report a case where total pancreatectomy and islet auto
      transplantation can be considered as a viable option for treatment of ampullary
      lesions in a setting where standard surgical options are suboptimal.

PMID- 22406612
TI  - An unusual case of double heterotopic pancreatic tissues in the same
      localization.

PMID- 22406613
TI  - Pain in chronic pancreatitis: from the bench to the bedside.

PMID- 22406614
TI  - On equilibrium properties of evolutionary multi-player games with random payoff
      matrices.
AB  - The analysis of equilibrium points in biological dynamical systems has been of
      great interest in a variety of mathematical approaches to biology, such as
      population genetics, theoretical ecology or evolutionary game theory. The maximal
      number of equilibria and their classification based on stability have been the
      primary subjects of these studies, for example in the context of two-player games
      with multiple strategies. Herein, we address a different question using
      evolutionary game theory as a tool. If the payoff matrices are drawn randomly
      from an arbitrary distribution, what are the probabilities of observing a certain
      number of (stable) equilibria? We extend the domain of previous results for the
      two-player framework, which corresponds to a single diploid locus in population
      genetics, by addressing the full complexity of multi-player games with multiple
      strategies. In closing, we discuss an application and illustrate how previous
      results on the number of equilibria, such as the famous Feldman-Karlin conjecture
      on the maximal number of isolated fixed points in a viability selection model,
      can be obtained as special cases of our results based on multi-player
      evolutionary games. We also show how the probability of realizing a certain
      number of equilibria changes as we increase the number of players and number of
      strategies.

PMID- 22406615
TI  - Selective depiction of susceptibility transitions using Laplace-filtered phase
      maps.
AB  - In this work, we aim to demonstrate the ability of Laplace-filtered three
      dimensional (3D) phase maps to selectively depict the susceptibility transitions
      in an object. To realize this goal, it is first shown that both the Laplace
      derivative of the z component of the static magnetic field in an object and the
      Laplacian of the corresponding phase distribution may be expected to be zero in
      regions of constant or linearly varying susceptibility and to be nonzero when
      there is an abrupt change in susceptibility, for instance, at a single point, a
      ridge, an interface, an edge or a boundary. Next, a method is presented by which
      the Laplace derivative of a 3D phase map can be directly extracted from the
      complex data, without the need for phase unwrapping or subtraction of a reference
      image. The validity of this approach and of the theory behind it is subsequently
      demonstrated by simulations and phantom experiments with exactly known
      susceptibility distributions. Finally, the potential of the Laplace derivative
      analysis is illustrated by simulations with a Shepp-Logan digital brain phantom
      and experiments with a gel phantom containing positive and negative focal
      susceptibility deviations.

PMID- 22406616
TI  - New insights in flat oyster Ostrea edulis resistance against the parasite Bonamia
      ostreae.
AB  - Bonamiosis due to the parasite Bonamia ostreae has been associated with massive
      mortality in flat oyster stocks in Europe. Control of the disease currently
      relies on disease management practices and transfer restriction. Previously,
      massal selections based on survival to challenge to infection with B. ostreae
      have been applied to produce flat oyster families with resistant progeny. In an
      attempt to understand the molecular mechanisms involved in disease resistance,
      differentially expressed sequence tags between resistant and wild Ostrea edulis
      haemocytes, both infected with the parasite, were identified using suppression
      subtractive hybridisation. Expression of seven ESTs has been studied using
      quantitative reverse-transcriptase PCR. The base-line expression of an
      extracellular superoxide dismutase, inhibitor of apoptosis (OeIAP), Fas ligand
      (OeFas-ligand) and Cathepsin B was significantly increased, whilst cyclophilin B
      appeared significantly decreased in resistant oysters. Considering their great
      interest for further studies, the open reading frames of the OeFas-ligand and
      OeIAP were completely sequenced.

PMID- 22406617
TI  - Effects of the anti-androgen, bicalutamide, in a reduced life-cycle study with
      the fathead minnow (Pimephales promelas).
AB  - In support of the environmental risk assessment (ERA) of the non-steroidal anti
      androgen bicalutamide, a reduced fish full life-cycle (FFLC) was conducted. The
      traditional FFLC is deemed to be the "gold standard" for evaluating the potential
      environmental impact of human pharmaceuticals, covering all life-stages and
      measuring long term effects. However, such studies require large numbers of
      animals and take considerable effort and time. The reduced FFLC, employed here,
      used fewer animals and was shorter in duration, yet still included sensitive life
      stages and measured long term effects to provide robust information in support of
      the ERA for an endocrine disrupting chemical. Fathead minnows (Pimephales
      promelas) were held in breeding pairs and their reproductive performance assessed
      over 28 days. Embryos from at least two pairs per treatment were subsequently
      grown up until 85 days post hatch and a subset allowed to spawn to assess the
      developmental and reproductive effects of the parental exposure on this F1
      generation. Fish were exposed in a flow-through system, at 25+/-1 degrees C.
      Nominal (mean measured) test concentrations of bicalutamide were 0.01 (0.055),
      0.10 (0.10), 1.0 (0.9), 10 (9.2) and 100 (92.1) MUg L-1. There were no
      significant effects on F0 fecundity or growth (wet weight and standard length),
      but a significant decrease in nuptial tubercle prominence (a secondary sexual
      characteristic, SSC) was observed in male fish exposed to 100 MUg L-1. In the F1
      generation, there were no treatment-related effects on hatching success or SSC,
      but survival was significantly decreased in fish exposed to the top concentration
      (100 MUg L-1. In female fish, wet weight and standard length were also
      significantly increased at this concentration. Gonadal histopathology revealed no
      treatment related effects on sex ratio, sexual differentiation or sexual
      development. However, there was a concentration related effect on gonad lesion
      severity in female fish exposed to 100 MUg L-1 and reproduction (number of eggs
      spawned) was also significantly reduced in breeding groups exposed to this
      concentration. Taking into account these data, the overall no observed effect
      concentration and lowest observed effect concentration values for bicalutamide
      were 10 and 100 MUg L-1, respectively.

PMID- 22406618
TI  - Do pollutants affect insecticide-driven gene selection in mosquitoes?
      Experimental evidence from transcriptomics.
AB  - The control of mosquitoes transmitting infectious diseases relies mainly on the
      use of chemical insecticides. However, the emergence of insecticide resistance
      threatens mosquito control programs. Until now, most research efforts have been
      focused on elucidating resistance mechanisms caused by insecticide treatments.
      Less attention has been paid to the impact of the mosquito chemical environment
      on insecticide-driven selection mechanisms. Here the mosquito Aedes aegypti was
      used as a model species to conduct laboratory experiments combining the exposure
      of mosquito larvae to a sub-lethal concentration of xenobiotics and their
      selection with the insecticide permethrin. After 10 generations, bioassays and a
      transcriptome profiling with a 15 k microarray were performed comparatively on
      all strains. The three selected strains showed a small but significant increase
      of permethrin resistance compared to the susceptible parental strain. Microarray
      analysis revealed that the transcription of many genes was altered by insecticide
      selection. Exposing larvae to sub-lethal concentrations of the pollutant
      fluoranthene or the insecticide permethrin prior to selection at each generation
      affected the selection of several genes, including those involved in
      detoxification, transport and cell metabolism. Genes potentially involved in
      permethrin resistance and cross-responses between xenobiotics and insecticide
      were identified. The present study investigated for the first time the impact of
      the presence of pollutants in mosquito environment on insecticide-driven
      selection mechanisms. Our results revealed that mosquitoes exposed to xenobiotics
      show a different adaptive response to insecticide selection pressure. This
      suggests that insect chemical environment can shape the long-term selection of
      metabolic mechanisms leading to insecticide resistance.

PMID- 22406619
TI  - Tumor angiogenesis mediated by myeloid cells is negatively regulated by CEACAM1.
AB  - Bv8 (prokineticin 2) expressed by Gr1(+)CD11b(+) myeloid cells is critical for
      VEGF-independent tumor angiogenesis. Although granulocyte colony-stimulating
      factor (G-CSF) has been shown to be a key inducer of Bv8 expression, the basis
      for Bv8 production in driving tumor angiogenesis is undefined. Because the cell
      adhesion molecule CEACAM1, which is highly expressed on Gr1(+)CD11b(+) myeloid
      cells, is known to regulate G-CSF receptor (G-CSFR) signaling, we hypothesized
      that CEACAM1 would regulate Bv8 production in these cells. In support of this
      hypothesis, we found that Bv8 expression was elevated in Gr1(+)CD11b(+) cells
      from Ceacam1-deficient mice implanted with B16 melanoma, increasing the
      infiltration of Gr1(+)CD11b(+) myeloid cells in melanoma tumors and enhancing
      their growth and angiogenesis. Furthermore, treatment with anti-Gr1 or anti-Bv8
      or anti-G-CSF monoclonal antibody reduced myeloid cell infiltration, tumor
      growth, and angiogenesis to levels observed in tumor-bearing wild-type (WT) mice.
      Reconstitution of CEACAM1-deficient mice with WT bone marrow cells restored tumor
      infiltration of Gr1(+)CD11b(+) cells along with tumor growth and angiogenesis to
      WT levels. Treatment of tumor-bearing WT mice with anti-CEACAM1 antibody limited
      tumor outgrowth and angiogenesis, albeit to a lesser extent. Tumor growth in
      Ceacam1-deficient mice was not affected significantly in Rag(-/-) background,
      indicating that CEACAM1 expression in T and B lymphocytes had a negligible role
      in this pathway. Together, our findings show that CEACAM1 negatively regulates
      Gr1(+)CD11b(+) myeloid cell-dependent tumor angiogenesis by inhibiting the G-CSF
      Bv8 signaling pathway.

PMID- 22406620
TI  - Novel MT1-MMP small-molecule inhibitors based on insights into hemopexin domain
      function in tumor growth.
AB  - Membrane type-1 matrix metalloproteinase (MT1-MMP) is a promising drug target in
      malignancy. The structure of MT1-MMP includes the hemopexin domain (PEX) that is
      distinct from and additional to the catalytic domain. Current MMP inhibitors
      target the conserved active site in the catalytic domain and, as a result,
      repress the proteolytic activity of multiple MMPs instead of MT1-MMP alone. In
      our search for noncatalytic inhibitors of MT1-MMP, we compared the protumorigenic
      activity of wild-type MT1-MMP with an MT1-MMP mutant lacking PEX (DeltaPEX). In
      contrast to MT1-MMP, DeltaPEX did not support tumor growth in vivo, and its
      expression resulted in small fibrotic tumors that contained increased levels of
      collagen. Because these findings suggested an important role for PEX in tumor
      growth, we carried out an inhibitor screen to identify small molecules targeting
      the PEX domain of MT1-MMP. Using the Developmental Therapeutics Program (National
      Cancer Institute/NIH), virtual ligand screening compound library as a source and
      the X-ray crystal structure of PEX as a target, we identified and validated a
      novel PEX inhibitor. Low dosage, intratumoral injections of PEX inhibitor
      repressed tumor growth and caused a fibrotic, DeltaPEX-like tumor phenotype in
      vivo. Together, our findings provide a preclinical proof of principle rationale
      for the development of novel and selective MT1-MMP inhibitors that specifically
      target the PEX domain.

PMID- 22406621
TI  - The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML and its oncogenic
      counterpart PML-RARA.
AB  - The ubiquitin-like SUMO proteins covalently modify protein substrates and
      regulate their functional properties. In a broad spectrum of cancers, the tumor
      suppressor PML undergoes ubiquitin-mediated degradation primed by CK2
      phosphorylation. Here, we report that the SUMO E3-ligase inhibitor PIAS1
      regulates oncogenic signaling through its ability to sumoylate PML and the PML
      RARA oncoprotein of acute promyelocytic leukemia (APL). PIAS1-mediated
      SUMOylation of PML promoted CK2 interaction and ubiquitin/proteasome-mediated
      degradation of PML, attenuating its tumor suppressor functions. In addition,
      PIAS1-mediated SUMOylation of PML-RARA was essential for induction of its
      degradation by arsenic trioxide, an effective APL treatment. Moreover, PIAS1
      suppression abrogated the ability of arsenic trioxide to trigger apoptosis in APL
      cells. Lastly, PIAS1 was also essential for PML degradation in non-small cell
      lung carcinoma (NSCLC) cells, and PML and PIAS1 were inversely correlated in
      NSCLC cell lines and primary specimens. Together, our findings reveal novel roles
      for PIAS1 and the SUMOylation machinery in regulating oncogenic networks and the
      response to leukemia therapy.

PMID- 22406622
TI  - S-glutathionylated serine proteinase inhibitors as plasma biomarkers in assessing
      response to redox-modulating drugs.
AB  - Many cancer drugs impact cancer cell redox regulatory mechanisms and disrupt
      redox homeostasis. Pharmacodynamic biomarkers that measure therapeutic efficacy
      or toxicity could improve patient management. Using immunoblot analyses and mass
      spectrometry, we identified that serpins A1 and A3 were S-glutathionylated in a
      dose- and time-dependent manner following treatment of mice with drugs that alter
      reactive oxygen or nitrogen species. Tandem mass spectrometry analyses identified
      Cys(256) of serpin A1 and Cys(263) of serpin A3 as the S-glutathionylated
      residues. In human plasma from cancer patients, there were higher levels of
      unmodified serpin A1 and A3, but following treatments with redox active drugs,
      relative S-glutathionylation of these serpins was higher in plasma from normal
      individuals. There is potential for S-glutathionylated serpins A1 and A3 to act
      as pharmacodynamic biomarkers for evaluation of patient response to drugs that
      target redox pathways.

PMID- 22406624
TI  - The toxic effects of Aroclor 1254 exposure on the osteoblastic cell line MC3T3-E1
      and its molecular mechanism.
AB  - Polychlorinated biphenyls (PCBs) are still prevalent in the environment despite
      the fact that they have been banned in many countries for several decades. Recent
      epidemiologic studies have demonstrated a link between PCBs exposure and
      pathological alterations of bone tissues. The aim of this study was to
      investigate the toxic effects of the PCBs mixture Aroclor 1254 on MC3T3-E1
      preosteoblasts and explore the underlying molecular mechanism. Different doses of
      Aroclor 1254 were used to treat MC3T3-E1 and the cell viability, apoptosis, ALP
      activity, intracellular calcium (Ca2+) level and oxidative stress response were
      measured. The expression level of related proteins TRPV6, Apaf-1 and Bax was
      evaluated with Western blot assay. The subcellular distribution of TRPV6 protein
      was detected with immunofluorescence assay. The results indicated that the higher
      dose of Aroclor 1254 (>10 mg/L) could inhibit the cell proliferation and induce
      apoptosis in MC3T3-E1. The ROS level following Aroclor 1254 exposure was elevated
      with the concentration, while the ALP activity and intracellular calcium (Ca2+)
      level decreased. After Aroclor 1254 exposure, the expression level of calcium
      transport related protein TRPV6 was down-regulated, while the expression level of
      apoptosis related proteins Apaf-1 and Bax up-regulated in a dose dependant
      manner. The immunofluorescence assay results showed that the expression of TRPV6
      in the cytoplasm was greatly suppressed after Aroclor 1254 exposure. In
      conclusion, Aroclor 1254 exposure could induce toxic effects in MC3T3-E1 as
      evidenced by inhibition of proliferation, induction of apoptosis and suppression
      of ALP activity. The ROS production and alteration of intracellular Ca2+ level
      induced by down-regulation of TRPV6 might involve the toxic effects, and cell
      apoptosis induced by Aroclor 1254 exposure is associated with the pro-apoptotic
      Apaf-1 pathway as well as alteration of Bcl-2/Bax ratio.

PMID- 22406623
TI  - Actively transported levodopa prodrug XP21279: a study in patients with Parkinson
      disease who experience motor fluctuations.
AB  - OBJECTIVE: The objectives of this study were to assess the pharmacokinetic
      profile, efficacy, and safety of XP21279 administered with carbidopa (CD) in
      subjects with Parkinson disease (PD) experiencing motor fluctuations and explore
      dose correspondence between CD-levodopa (LD) and XP21279 administered with CD.
      METHODS: Subjects received CD-LD 3 or 4 times daily for 2 weeks, followed by
      XP21279 plus CD 3 times daily for 2 weeks at fixed dosing times, allowing dose
      adjustment to optimize clinical response, in this multiple-dose, multicenter,
      open-label, 2-period, sequential-treatment study. Pharmacokinetic parameters,
      including LD exposure, were assessed over 16 hours on the last day of each
      treatment period. Levodopa exposure variability was assessed for each treatment
      using the absolute % deviation from average concentration (Cavg) in each subject.
      Efficacy assessments included daily self-ratings of OFF time, ON time, and
      dyskinesias. RESULTS: XP21279 provided significantly less variability in LD
      concentration compared with CD-LD (P < 0.05) in 10 PD subjects with motor
      fluctuations, consistent with lower peak-to-trough fluctuation for XP21279.
      Patterns of percentage of subjects OFF were consistent with the LD concentration
      time profiles for each respective treatment. Compared with CD-LD treatment, 6 of
      10 study completers experienced reduction of 30% or greater in average daily OFF
      time during the last 4 days in the XP21279 treatment period. XP21279 resulted in
      an increase in the time spent ON without troublesome dyskinesias, and the mean
      time to ON after the first morning XP21279 dose was not delayed, as compared with
      CD-LD. CONCLUSIONS: XP21279 provided improved pharmacokinetic performance
      (highlighted by reduction in variability of LD concentration) compared with CD-LD
      and therefore may provide better control of PD motor fluctuations.

PMID- 22406625
TI  - From red to blue to far-red in Lhca4: how does the protein modulate the spectral
      properties of the pigments?
AB  - The first event of photosynthesis is the harvesting of solar energy by a large
      array of pigments. These pigments are coordinated to proteins that organize them
      to assure efficient excitation energy transfer. The protein plays an essential
      role in tuning the spectroscopic properties of the pigments, by determining their
      site energy and/or by favoring pigment-pigments interactions. Here we investigate
      how the protein modulates the pigment properties by using a single-point-mutation
      approach. We monitor changes in the low-energy absorption/emission band of Lhca4,
      which is well separated from the bulk absorption and thus represents an
      attractive model system. Moreover, it was recently shown that Lhca4 exists in at
      least two conformations, a dominating one emitting at 720 nm and a second one
      emitting at 685 nm (Kruger et al. PNAS 2011). Here we show that a single amino
      acid substitution (from Asn to Gln, which are both chlorophyll-binding residues
      and only differ for one C-C bond), moves the equilibrium almost completely
      towards the 685-nm conformation. This indicates that small changes in the protein
      can have a large effect on the properties of the pigments. We show that His99,
      which was suggested to coordinate a red-absorbing chlorophyll (Melkozernov and
      Blankenship, JBC 2003), is not a chlorophyll ligand. We also show that single
      amino-acid substitutions nearby the chlorophylls allow to tune the emission
      spectrum of the pigments over a wide range of wavelengths and to modulate the
      excited-state lifetimes of the complex. These findings are discussed in the light
      of previously proposed non-photochemical quenching models.

PMID- 22406626
TI  - Probing the role of chloride in Photosystem II from Thermosynechococcus elongatus
      by exchanging chloride for iodide.
AB  - The active site for water oxidation in Photosystem II (PSII) goes through five
      sequential oxidation states (S(0) to S(4)) before O(2) is evolved. It consists of
      a Mn(4)CaO(5) cluster and Tyr(Z), a redox-active tyrosine residue. Chloride ions
      have been known for long time to be required for the function of the enzyme.
      However, X-ray data have shown that they are located about 7A away from the
      Mn(4)CaO(5) cluster, a distance that seems too large to be compatible with a
      direct involvement of chloride in the water splitting chemistry. We have
      investigated the role of this anion by substituting I(-) for Cl(-) in the
      cyanobacterium Thermosynechococcus elongatus with either Ca(2+) or Sr(2+)
      biosynthetically assembled into the Mn(4) cluster. The electron transfer steps
      affected by the exchanges were investigated by time-resolved UV-visible
      absorption spectroscopy, time-resolved EPR at room temperature and low
      temperature cw-EPR spectroscopy. In both Ca-PSII and Sr-PSII, the Cl(-)/I(-)
      exchange considerably slowed down the two S(3)Tyr(Z)(*)->(S(3)Tyr(Z)(*))'->S(0)
      reactions in which the fast phase, S(3)Tyr(Z)(*)->(S(3)Tyr(Z)(*))', reflects the
      electrostatically triggered expulsion of one proton from the catalytic center
      caused by the positive charge near/on Tyr(Z)(*) and the slow phase corresponds to
      the S(0) and O(2) formations and to a second proton release. The t(1/2) for S(0)
      formation increased from 1.1 ms in Ca/Cl-PSII to ~6 ms in Ca/I-PSII and from 4.8
      ms in Sr/Cl-PSII to ~45 ms in Sr/I-PSII. In all cases the Tyr(Z)(*) reduction was
      the limiting step. The kinetic effects are interpreted by a model in which the
      Ca(2+) binding site and the Cl(-) binding site, although spatially distant,
      interact. This interaction is likely mediated by the H-bond and/or water
      molecules network(s) connecting the Cl(-) and Ca(2+) binding sites by which
      proton release may be channelled.

PMID- 22406627
TI  - Effect of mtDNA point mutations on cellular bioenergetics.
AB  - This overview discusses the results of research on the effects of most frequent
      mtDNA point mutations on cellular bioenergetics. Thirteen proteins coded by mtDNA
      are crucial for oxidative phosphorylation, 11 of them constitute key components
      of the respiratory chain complexes I, III and IV and 2 of mitochondrial ATP
      synthase. Moreover, pathogenic point mutations in mitochondrial tRNAs and rRNAs
      generate abnormal synthesis of the mtDNA coded proteins. Thus, pathogenic point
      mutations in mtDNA usually disturb the level of key parameter of the oxidative
      phosphorylation, i.e. the electric potential on the inner mitochondrial membrane
      (Deltapsi), and in a consequence calcium signalling and mitochondrial dynamics in
      the cell. Mitochondrial generation of reactive oxygen species is also modified in
      the mutated cells. The results obtained with cultured cells and describing
      biochemical consequences of mtDNA point mutations are full of contradictions.
      Still they help elucidate the biochemical basis of pathologies and provide a
      valuable tool for finding remedies in the future. This article is part of a
      Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).

PMID- 22406628
TI  - Biomonitoring measures absorption and exposure.

PMID- 22406630
TI  - Asthma induced by exposure to spray polyurethane foam insulation in a residential
      home.

PMID- 22406631
TI  - Validation of the sex difference in the trend of carotid artery intima media
      thickness by the number of metabolic components:  is this a result related to
      occupational factors?

PMID- 22406633
TI  - Post-hire asthma among insect-rearing workers.
AB  - OBJECTIVE: To evaluate the incidence of post-hire asthma (PHA) among insect
      rearing workers, defined as asthma, the symptoms of which appeared after hire at
      the current workplace. METHODS: We surveyed the health of workers at three insect
      rearing facilities and an associated office facility. We calculated the incidence
      and estimated hazard ratios for PHA. RESULTS: Post-hire asthma incidence in 157
      insect-rearing workers was 16.2 per 1000 person-years compared with 9.2 per 1,000
      person-years in 70 office workers. Workers with predominant exposure to
      Lepidoptera had an incidence of 26.9 per 1000 person-years and a hazard ratio of
      5.5 (95% confidence interval: 1.6 to 23.9) adjusted for sex, race, and parental
      asthma. In contrast, the presence of specific immunoglobulin E to Lepidoptera
      antigens was not associated with PHA. CONCLUSION: Insect-rearing workers had a
      high incidence of PHA, primarily accounted for by workplace exposure to
      Lepidoptera.

PMID- 22406634
TI  - What is the ICOH Code of Ethics and how is it different from the ACOEM "Code of
      Ethics"?

PMID- 22406637
TI  - What we have learned about pancreatic cancer from mouse models.

PMID- 22406639
TI  - Indications and long-term clinical outcomes in 282 patients with pelvic
      exenteration for advanced or recurrent cervical cancer.
AB  - OBJECTIVE: The aim of this study was to summarize the clinical experience at our
      clinic with pelvic exenteration as a treatment for cervical cancer with special
      regard to the indications and outcomes of specific patient groups. METHODS:
      Medical records of 282 women who underwent pelvic exenteration to treat cervical
      cancer were analyzed. RESULTS: In total, 70 patients (25%) underwent primary
      exenteration, and 212 (75%) underwent secondary exenteration. Exenteration was
      anterior for 14 (5%) patients, posterior for 6 (2%) and total for 262 (93%). The
      overall survival (OS) of the 282 patients was 41% at 5 years and 37% at 10 years.
      The disease-free survival at 5 years was 61%. For 133 patients for whom pelvic
      exenteration was a curative procedure, the OS was 64% at 5 years and 57% at 10
      years. For cases of pelvic exenteration as a palliative intervention, the OS was
      19% at 5 years and 18% at 10 years. No difference was seen in the OS at 5 years
      between patients who received primary and secondary operations. No significant
      difference in the OS was found regardless of whether the patients had positive
      pelvic lymph nodes, whereas in cases of paraaortic lymph node metastasis, the OS
      was significantly lower. Out of all of the procedures, 139 (49%) involved no
      perioperative or postoperative complications. One major complication was reported
      for 72 (26%) patients, two complications occurred for 42 patients (15%) and more
      than three complications were noted for 29 (10%) patients. CONCLUSION: Pelvic
      exenteration is an effective technique with a high percentage of long-term
      survivors. To the best of our knowledge, our study involves the largest published
      number of patients treated with pelvic exenteration for a single gynecological
      cancer and shows that previous contraindications for pelvic exenteration, such as
      lymph node metastasis (especially when confined to the pelvic lymph nodes), older
      age or palliative intent, should be reconsidered.

PMID- 22406638
TI  - Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or
      peritoneum.
AB  - OBJECTIVE: To determine whether hormonal therapies have efficacy in patients with
      recurrent low-grade serous carcinoma of the ovary or peritoneum. METHODS: We
      searched departmental databases for patients with histologically-confirmed,
      evaluable, recurrent low-grade serous ovarian or peritoneal carcinoma who
      received hormonal therapy at our institution between 1989 and 2009. We
      retrospectively reviewed patients' medical records for demographic, disease,
      hormonal therapy, and estrogen receptor and progesterone receptor expression
      data. We used the Response Evaluation Criteria in Solid Tumors version 1.1 to
      determine patients' responses to hormonal therapy. Because patients could have
      received more than one evaluable hormonal therapy regimen, we chose to define the
      outcome metric as "patient-regimens." Median time to disease progression (TTP)
      and overall survival (OS) were also calculated. Regression analysis was also
      performed. RESULTS: We identified 64 patients with recurrent low-grade serous
      carcinoma of the ovary or peritoneum. Patients' median TTP and median OS were 7.4
      and 78.2 months, respectively. Patients received 89 separate hormonal patient
      regimens, which produced an overall response rate of 9% (6 complete responses and
      2 partial responses). Sixty-one percent of the patient-regimens resulted in a
      progression-free survival duration of at least 6 months. Patient-regimens
      involving ER+/PR+ disease produced a longer median TTP (8.9 months) than patient
      regimens involving ER+/PR- disease did (6.2 months; p=0.053). This difference
      approached but did not reach statistical significance. CONCLUSIONS: Hormonal
      therapies have moderate anti-tumor activity in patients with recurrent low-grade
      serous carcinoma of the ovary or peritoneum. Further study to determine whether
      ER/PR expression status is a predictive biomarker for this rare cancer subtype is
      warranted.

PMID- 22406640
TI  - KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion
      transport in the distal nephron.
AB  - Familial hyperkalemic hypertension (FHHt) is a Mendelian form of arterial
      hypertension that is partially explained by mutations in WNK1 and WNK4 that lead
      to increased activity of the Na(+)-Cl(-) cotransporter (NCC) in the distal
      nephron. Using combined linkage analysis and whole-exome sequencing in two
      families, we identified KLHL3 as a third gene responsible for FHHt. Direct
      sequencing of 43 other affected individuals revealed 11 additional missense
      mutations that were associated with heterogeneous phenotypes and diverse modes of
      inheritance. Polymorphisms at KLHL3 were not associated with blood pressure. The
      KLHL3 protein belongs to the BTB-BACK-kelch family of actin-binding proteins that
      recruit substrates for Cullin3-based ubiquitin ligase complexes. KLHL3 is
      coexpressed with NCC and downregulates NCC expression at the cell surface. Our
      study establishes a role for KLHL3 as a new member of the complex signaling
      pathway regulating ion homeostasis in the distal nephron and indirectly blood
      pressure.

PMID- 22406641
TI  - Generation of functional insulin-producing cells in the gut by Foxo1 ablation.
AB  - Restoration of regulated insulin secretion is the ultimate goal of therapy for
      type 1 diabetes. Here, we show that, unexpectedly, somatic ablation of Foxo1 in
      Neurog3(+) enteroendocrine progenitor cells gives rise to gut insulin-positive
      (Ins(+)) cells that express markers of mature beta cells and secrete bioactive
      insulin as well as C-peptide in response to glucose and sulfonylureas. Lineage
      tracing experiments showed that gut Ins(+) cells arise cell autonomously from
      Foxo1-deficient cells. Inducible Foxo1 ablation in adult mice also resulted in
      the generation of gut Ins(+) cells. Following ablation by the beta-cell toxin
      streptozotocin, gut Ins(+) cells regenerate and produce insulin, reversing
      hyperglycemia in mice. The data indicate that Neurog3(+) enteroendocrine
      progenitors require active Foxo1 to prevent differentiation into Ins(+) cells.
      Foxo1 ablation in gut epithelium may provide an approach to restore insulin
      production in type 1 diabetes.

PMID- 22406642
TI  - Whole-genome analysis of diverse Chlamydia trachomatis strains identifies
      phylogenetic relationships masked by current clinical typing.
AB  - Chlamydia trachomatis is responsible for both trachoma and sexually transmitted
      infections, causing substantial morbidity and economic cost globally. Despite
      this, our knowledge of its population and evolutionary genetics is limited. Here
      we present a detailed phylogeny based on whole-genome sequencing of
      representative strains of C. trachomatis from both trachoma and lymphogranuloma
      venereum (LGV) biovars from temporally and geographically diverse sources. Our
      analysis shows that predicting phylogenetic structure using ompA, which is
      traditionally used to classify Chlamydia, is misleading because extensive
      recombination in this region masks any true relationships present. We show that
      in many instances, ompA is a chimera that can be exchanged in part or as a whole
      both within and between biovars. We also provide evidence for exchange of, and
      recombination within, the cryptic plasmid, which is another key diagnostic
      target. We used our phylogenetic framework to show how genetic exchange has
      manifested itself in ocular, urogenital and LGV C. trachomatis strains, including
      the epidemic LGV serotype L2b.

PMID- 22406643
TI  - Reverse breeding in Arabidopsis thaliana generates homozygous parental lines from
      a heterozygous plant.
AB  - Traditionally, hybrid seeds are produced by crossing selected inbred lines. Here
      we provide a proof of concept for reverse breeding, a new approach that
      simplifies meiosis such that homozygous parental lines can be generated from a
      vigorous hybrid individual. We silenced DMC1, which encodes the meiotic
      recombination protein DISRUPTED MEIOTIC cDNA1, in hybrids of A. thaliana, so that
      non-recombined parental chromosomes segregate during meiosis. We then converted
      the resulting gametes into adult haploid plants, and subsequently into homozygous
      diploids, so that each contained half the genome of the original hybrid. From 36
      homozygous lines, we selected 3 (out of 6) complementing parental pairs that
      allowed us to recreate the original hybrid by intercrossing. In addition, this
      approach resulted in a complete set of chromosome-substitution lines. Our method
      allows the selection of a single choice offspring from a segregating population
      and preservation of its heterozygous genotype by generating homozygous founder
      lines.

PMID- 22406645
TI  - Virulence profiles in uropathogenic Escherichia coli isolated from pregnant women
      and children with urinary tract abnormalities.
AB  - Uropathogenic Escherichia coli is the leading etiologic agent of urinary tract
      infections, encompassing a highly heterogeneous group of strains. Although many
      putative urovirulence factors have been described, none of them appear in all
      uropathogenic E. coli strains, a fact that suggests that this group would be
      composed of different pathogenic subgroups. In this work, a study was performed
      on two collections of E. coli isolates proceeding from urine cultures from two
      groups of patients with urinary tract infection: pregnant women and children with
      urinary tract abnormalities. The isolates were analyzed for their virulence
      content and for their phylogeny by means of PCR determinations and of phenotypic
      assays. Associations among the virulence traits analyzed were searched for and
      this approach led to the identification of five urovirulence profiles. From a
      total of 230 isolates, 123 (53%) could be assigned to one of these profiles. A
      few loci appeared as markers of these profiles so that their presence allowed
      predicting the general virulence content of the strains. It is presumed that
      these conserved associations among the virulence functions would be devoted to
      ensure the coherence of the bacterial pathogenic strategy. In addition, three
      profiles appeared with significantly different frequencies depending on the host
      of origin of the isolates, indicating the existence of a correlation between the
      virulence content of the strains and their host specificity.

PMID- 22406646
TI  - Diving for drugs: tunicate anticancer compounds.
AB  - The marine biosphere boasts tremendous biodiversity replete with structurally
      unique, active and selective secondary metabolites. Bioprospecting for antitumor
      compounds has been rewarding, and tunicates have been especially successful in
      yielding prospective cancer therapies. These compounds are now subjected to
      clinical trials in Europe and the USA. With the ongoing search for potent and
      specific anticancer drugs, in this article we discuss the unique perspectives,
      compounds and opportunities afforded by this rich source of potential
      pharmaceuticals. We discuss marine-derived antitumor drugs, their structures, and
      their various types and levels of antitumor activities in bench and bedside
      efforts.

PMID- 22406644
TI  - Common genetic variants at the 11q13.3 renal cancer susceptibility locus
      influence binding of HIF to an enhancer of cyclin D1 expression.
AB  - Although genome-wide association studies (GWAS) have identified the existence of
      numerous population-based cancer susceptibility loci, mechanistic insights remain
      limited, particularly for intergenic polymorphisms. Here, we show that
      polymorphism at a remote intergenic region on chromosome 11q13.3, recently
      identified as a susceptibility locus for renal cell carcinoma, modulates the
      binding and function of hypoxia-inducible factor (HIF) at a previously
      unrecognized transcriptional enhancer of CCND1 (encoding cyclin D1) that is
      specific for renal cancers characterized by inactivation of the von Hippel-Lindau
      tumor suppressor (pVHL). The protective haplotype impairs binding of HIF-2,
      resulting in an allelic imbalance in cyclin D1 expression, thus affecting a link
      between hypoxia pathways and cell cycle control.

PMID- 22406647
TI  - UTE T2* mapping detects sub-clinical meniscus degeneration.

PMID- 22406648
TI  - Effects of type I collagen coating on titanium osseointegration:
      histomorphometric, cellular and molecular analyses.
AB  - The investigation of titanium (Ti) surface modifications aiming to increase
      implant osseointegration is one of the most active research areas in dental
      implantology. This study was carried out to evaluate the benefits of coating Ti
      with type I collagen on the osseointegration of dental implants. Acid etched Ti
      implants (AETi), either untreated or coated with type I collagen (ColTi), were
      placed in dog mandibles for three and eight weeks for histomorphometric, cellular
      and molecular evaluations of bone tissue response. While the histological aspects
      were essentially the same with both implants being surrounded by lamellar bone
      trabeculae, histomorphometric analysis showed more abundant bone formation in
      ColTi, mainly at three weeks. Cellular evaluation showed that cells harvested
      from bone fragments in close contact with ColTi display lower proliferative
      capacity and higher alkaline phosphatase activity, phenotypic features associated
      with more differentiated osteoblasts. Confirming these findings, molecular
      analyses showed that ColTi implants up-regulates the expression of a panel of
      genes well known as osteoblast markers. Our results present a set of evidences
      that coating AETi with collagen fastens the osseointegration by stimulating bone
      formation at the cellular and molecular levels, making this combination of
      morphological and biochemical modification a promising approach to treat Ti
      surfaces.

PMID- 22406649
TI  - Interventions to improve anticoagulation with warfarin.
AB  - INTRODUCTION: This study aimed to investigate potential drug-drug interactions
      (pDDIs) with warfarin to minimize them, assess the acceptability of
      pharmaceutical interventions by the medical team and the impact on the
      international normalized ratio (INR) results. METHODS: This pertains to a
      prospective study involving inpatients who started warfarin therapy in a
      university hospital located in southern Brazil. The pDDIs with warfarin were
      identified using the interaction screening program Drug-Reax, Micromedex
      Healthcare Series 1.0. RESULTS: Two hundred and two inpatients were monitored.
      The mean of 10 different drugs was prescribed for each patient (SD = 3.6). At
      least 1 major or moderate pDDIs with warfarin per patient was observed, the mean
      was 3.6 (SD = 1.6). The most common pDDIs with warfarin involved in the increase
      of anticoagulation effect were enoxaparin (32.2%), simvastatin (27.6%),
      omeprazole (22.5%), and tramadol (21.5%). For 32 patients (15.8%), interventions
      were rejected, and they had a higher risk (relative risk= 2.17; 95% confidence
      interval 1.10-4.27) for abnormal test results (INR > 5). Multivariate analysis
      showed that age, length of hospital stay, exposure to >=4 major or moderate
      pDDIs, and refusal of pharmacist recommendations contribute significantly to the
      patient's INR result >5. Consequently, the risk of bleeding is increased.
      CONCLUSIONS: Major and moderate pDDIs with warfarin are very common in inpatients
      and are associated with INR results outside the therapeutic range. Pharmaceutical
      interventions concerning the management of interactions by providing information
      to physicians can improve the patient safety.

PMID- 22406650
TI  - Therapeutic drug monitoring of beta-lactam antibiotics in burns patients--a one
      year prospective study.
AB  - BACKGROUND: Beta-lactams are first-line antibiotics for the management of
      superficial infections due to burn injury. There is sparse data available on
      therapeutic drug monitoring (TDM) in patients with burns in a ward setting. This
      study was conducted to evaluate the utility of a beta-lactam TDM program in a
      cohort of burn injury patients in a ward environment. METHODS: Steady-state blood
      samples were collected immediately before a scheduled dose. The therapeutic
      concentration targets assessed were (1) free antibiotic concentrations exceeding
      the minimum inhibitory concentration (MIC; fT > MIC) and (2) free concentrations
      >=4* MIC of the known or suspected pathogen (fT > 4* MIC). The duration of
      therapy was also assessed. RESULTS: A total of 50 patients were included for TDM
      over a 12-month period. The mean (+/-SD) age was 49 +/- 16 years. The mean
      percent total body surface area burn was 17 +/- 13%. The mean serum creatinine
      concentration was 86 +/- 20 MUmole/L. Sixty percent of the patients did not
      achieve fT > MIC, and only 18% achieved the higher target of fT > 4* MIC.
      Although all the patients achieved a positive clinical outcome, the duration of
      antibiotic treatment was shorter in patients who achieved fT > MIC compared with
      those who did not (4.2 +/- 1.1 versus 5.3 +/- 2.3 days; P = 0.03). CONCLUSIONS:
      We found TDM to be a reliable intervention for burn injury patients in a ward
      environment. This study supports pharmacokinetic data that burns patients may be
      at risk of subtherapeutic dosing, which may prolong the duration of antibiotic
      therapy.

PMID- 22406651
TI  - Suspected opioid overdose case resolved by CYP2D6 genotyping.
AB  - A 14-year-old female with suspected narcotic overdose had CYP2D6 genotyping
      performed to verify opiate intoxication. The role of pharmacogenetics in pain
      management and individualization of opiate pharmacotherapy is discussed.

PMID- 22406652
TI  - Intrapatient and interpatient pharmacokinetic variability of raltegravir in the
      clinical setting.
AB  - INTRODUCTION: Raltegravir (RAL) is the first in class integrase inhibitor and is
      licensed for administration at 400 mg twice daily. RAL pharmacokinetics are
      characterized by high interpatient variability and recently RAL plasma exposure
      has been correlated with efficacy. RAL is primarily metabolized by
      glucuronidation via uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and
      UGT1A1*28 considered to be the main genetic variant associated with decreased
      UGT1A1 expression. This study investigated variability in RAL trough plasma
      concentrations (Ctrough) in the clinical setting, the effect of UGT1A1*28 and
      concomitant antiretrovirals. METHODS: A total of 86 patients, from Turin, Italy,
      and Madrid, Spain, were included in the analysis. Blood samples were obtained 10
      14 hours postdose. Genotyping for UGT1A1*28 was conducted by sequencing. RESULTS:
      High interpatient and intrapatient variabilities were observed; 13 patients had
      >=3 samples available, and the median coefficient of variation was 128 (64-265).
      Coadministration of RAL with atazanavir (ATV, n = 9) resulted in higher
      raltegravir Ctrough, 517 (307-2706) ng/mL when compared with patients not
      receiving ATV (n = 77) 223 (95-552; P = 0.02). UGT1A1*28 did not influence RAL
      plasma exposure. DISCUSSION: We have documented large intersubject and
      intrasubject variabilities in RAL plasma concentrations and confirmed the
      interaction with ATV. Further studies are required to better understand the
      mechanisms that influence the pharmacokinetics of RAL.

PMID- 22406653
TI  - Quantification of tacrolimus and three demethylated metabolites in human whole
      blood using LC-ESI-MS/MS.
AB  - BACKGROUND: A bioalanytical method for the quantification of tacrolimus (TAC) and
      3 metabolites, 13-O, 15-O, and 31-O-demethylated TAC (M-I, M-III, and M-II) in
      human whole blood using liquid chromatography, electrospray ionization, tandem
      mass spectrometry (LC-ESI-MS/MS) was developed and validated. METHOD: The
      analytes were extracted from 85 MUL of blood by protein precipitation followed by
      solid-phase extraction and a concentration step. The analytes and the internal
      standard (IS, ascomycin) were separated on a C18 column using a slow gradient
      mobile phase elution, with an analysis time of 3.3 minutes. The ammonium-adduct
      ions with transitions of m/z 821.5 > 768.7 (TAC), 807.5 > 754.7 (M-I, M-III, M
      II), and 809.4 > 756.7 (IS) were measured in selected reaction monitoring mode
      using electrospray ionization. RESULTS: Measuring ranges were 0.1-50 ng/mL for M
      II, M-III, and TAC and 0.15-39 ng/mL for M-I. Imprecision in quantification was
      <20% for all analytes, whereas accuracy was within +/-20%. Recovery was
      calculated to be >50% for all analytes. The sample's stability was proven for 1
      month at -20 degrees C and 72 hours at room temperature. Three freeze-thaw cycles
      had no significant effect on the stability. The prepared samples were stable at
      least 16 hours at 8 degrees C. Analysis of 53 patient samples resulted in average
      concentrations of 7.2 for TAC, 0.8 for M-I, 0.4 for M-III, and 0.2 ng/mL for M
      II. The total metabolite concentration was 17% (4%-52%) of the TAC concentration.
      The TAC concentration measured by LC-MS/MS was 36.1% +/- 27.1% lower than by
      immunochemical (enzyme multiplied immunoassay technique) analysis. When adding
      the metabolite crossreactivity in the presence of TAC, the difference between the
      2 methods was still 29.8% +/- 28.3%, indicating that the overestimation of TAC
      concentration of enzyme multiplied immunoassay technique compared with liquid
      chromatography-tandem mass spectrometry cannot only be ascribed to the
      demethylated metabolites. CONCLUSIONS: An LC-ESI-MS/MS method for the
      quantitative analysis of TAC and 3 metabolites, using a 2-step sample preparation
      was successfully developed, validated, and applied on 53 patient samples.

PMID- 22406654
TI  - Inosine triphosphatase polymorphisms and ribavirin pharmacokinetics as
      determinants of ribavirin-associate anemia in patients receiving standard anti
      HCV treatment.
AB  - BACKGROUND: Functional variants of inosine triphosphatase (ITPA) were recently
      found to protect against ribavirin (RBV)-induced hemolytic anemia. However, no
      definitive data are yet available on the role of plasma RBV concentrations on
      hemoglobin (Hb) decrement. Moreover, no data have been published on the possible
      interplay between these 2 factors. METHODS: A retrospective analysis included 167
      patients. The ITPA variants rs7270101 and rs1127354 were genotyped and tested
      using the chi test for association with Hb reduction at week 4. We also
      investigated, using multivariate logistic regression, the impact of RBV plasma
      exposure on Hb concentrations. RESULTS: Both single nucleotide polymorphisms were
      associated with Hb decrease. The carrier of at least 1 variant allele in the
      functional ITPA single nucleotide polymorphisms was associated with a lower
      decrement of Hb (-1.1 g/dL), as compared with patients without a variant allele (
      2.75 g/dL; P = 4.09 * 10). RBV concentrations were not influenced by ITPA
      genotypes. A cut-off of 2.3 MUg/mL of RBV was found to be associated with anemia
      (area-under-receiver operating characteristic = 0.630, sensitivity = 50.0%, and
      specificity = 69.5%, P = 0.008). In multivariate logistic regression analyses,
      the carrier of a variant allele (P = 0.005) and plasma RBV concentrations <2.3
      MUg/mL (P = 0.016) were independently associated with protection against
      clinically significant anemia at week 4. CONCLUSIONS: Although no direct
      relationship was found between ITPA polymorphisms and plasma RBV concentrations,
      both factors were shown to be significantly associated with anemia. A
      multivariate regression model based on ITPA genetic polymorphisms and RBV trough
      concentration was developed for predicting the risk of anemia. By relying upon
      these 2 variables, an individualized management of anemia seems to be feasible in
      recipients of pegylated interferon-RBV therapy.

PMID- 22406655
TI  - Pharmacokinetic behavior and appraisal of intravenous busulfan dosing in infants
      and older children:  the results of a population pharmacokinetic study from a
      large pediatric cohort undergoing hematopoietic stem-cell transplantation.
AB  - BACKGROUND: Intravenous (IV) busulfan (Bu) dosing approved in Europe based on 5
      body weight (BW) strata has been validated for targeting Bu exposures in children
      undergoing hematopoietic stem-cell transplantation and with mostly malignant
      diseases. The authors conducted an observational study aiming to investigate the
      behavior and ontogeny of IV Bu pharmacokinetic (PK) disposition, and to
      reevaluate the consistency of the BW-based dosing in very young children with
      rare diseases. METHODS: The observational study comprised 115 patients, mostly
      infants with immunodeficiencies and metabolic inherited disorders and with
      altered liver function and/or iron overload. Additional data (90 children, mostly
      malignant diseases) were pooled with the first data set. The overall data (205
      children aged from 10 days to 15 years) were analyzed using population PK
      modeling. RESULTS: The BW remained the main determinant of IV Bu PK, and no
      further covariate effect was identified. Bu clearance (CL) variability was best
      described by BW allometric functions. Increase of drug CL with the child's growth
      was faster in younger children. This pattern is likely related to the maturation
      of GSTA1 enzymes during infancy and was accounted for in the model by estimating
      a higher BW allometric exponent in children <9 kg compared with that in children
      >=9 kg. IV Bu PK was not modified in children with altered liver function and/or
      iron overload, and no disease specific difference was observed. Bu dosing either
      adjusted according to the final model or with the approved EU labeling yields
      similar targeting performances. For both dosing strategies, the percent of
      patients achieving the therapeutic area under the curve window (900-1500
      MUmole.min/L were 60% and 70%-90% in children <9 and >=9 kg, respectively.
      CONCLUSIONS: A population PK model accounting for the highest Bu CL in the
      youngest patients was validated on training and evaluation data sets. The BW
      based dosing strategy recommended in Europe proved to be consistent on a large
      paediatric cohort representative of the population heterogeneity observed in
      hematopoietic stem-cell transplantation.

PMID- 22406656
TI  - Tacrolimus pharmacokinetics of once- versus twice-daily formulations in de novo
      kidney transplantation: a substudy of a randomized phase III trial.
AB  - BACKGROUND: Tacrolimus is a well-established immunosuppressive agent for the
      treatment and prevention of solid organ graft rejection. It is available as an
      immediate-release, twice-daily formulation (Tacrolimus BID) and a prolonged
      release, once-daily formulation (Tacrolimus QD). In a previous study of the
      pharmacokinetics (PK) of these formulations, mean systemic exposure [area under
      the curve from 0 to 24 hours (AUC0-24)] of tacrolimus on day 1 was approximately
      30% lower for Tacrolimus QD than for Tacrolimus BID; by day 14, systemic exposure
      was similar; however, the mean dose of Tacrolimus QD was higher to achieve
      similar systemic exposure as Tacrolimus BID. METHODS: To further compare the PK
      of the tacrolimus formulations during the first 2 weeks posttransplant, a
      substudy was performed in a subset of patients enrolled into a phase III trial in
      de novo kidney transplant recipients comparing Tacrolimus QD and Tacrolimus BID.
      To minimize the difference in exposure observed in the earlier study, tacrolimus
      therapy was initiated before transplant. The PK analysis set comprised 34
      patients (17 patients per treatment group) who had 4 complete PK profiles and no
      major PK-related protocol violations. RESULTS: Mean AUC0-24 of tacrolimus on day
      1 was approximately 16% lower for Tacrolimus QD than for Tacrolimus BID, although
      by day 3 onward, the exposure was similar between treatment groups. Analysis of
      dose-normalized AUC0-24 (dose normalized to 0.1 mg/kg) showed a similar pattern.
      There was a good correlation between AUC0-24 and concentration of tacrolimus at
      24 hours postdose for both formulations (Tacrolimus QD, r = 0.87; Tacrolimus BID,
      r = 0.92), and the slope of the line of best fit was similar. CONCLUSIONS: These
      results suggest that initiating tacrolimus therapy before transplant reduces the
      difference in exposure between Tacrolimus QD and Tacrolimus BID.

PMID- 22406657
TI  - Population pharmacokinetics of carbamazepine in elderly patients.
AB  - BACKGROUND: Carbamazepine is a commonly used antiepileptic drug in elderly
      patients. This study analyzed prospective data collected as part of a randomized,
      double-blinded trial of newly diagnosed epilepsy patients. The aims of this study
      were to determine the pharmacokinetic parameters and their variability of
      carbamazepine in elderly patients and to quantify the effect of covariates on
      these parameters. METHODS: Prospectively collected carbamazepine concentrations
      from 121 patients aged 60 years or older were used to develop a population
      pharmacokinetic model. Data were analyzed by a nonlinear mixed effects model
      (NONMEM). A 1-compartment model with first-order absorption and elimination was
      used to characterize the time course of carbamazepine concentration. Model
      evaluation and the predictive performance of the final model were assessed using
      the nonparametric bootstrap approach. RESULTS: The apparent clearance (CL/F) of
      carbamazepine in this community-dwelling elderly population was estimated to be
      3.59 L/h with an interindividual variability of 18.1%. The CL/F increases 23% in
      patients comedicated with phenytoin. The volume of distribution (V/F) was
      estimated to be 102 L with an interindividual variability of 74.7%. CONCLUSIONS:
      Carbamazepine clearance was not associated with body weight or any
      parameterization of body size nor was age or race or any marker of hepatic or
      renal function in community dwelling elderly patients. Elderly patients on
      concurrent phenytoin therapy may require a smaller 23% higher dose on average,
      about half that reported for younger patients.

PMID- 22406658
TI  - Retrieval per se is not sufficient to trigger reconsolidation of human fear
      memory.
AB  - Ample evidence suggests that consolidated memories, upon their retrieval, enter a
      labile state, in which they might be susceptible to change. It has been proposed
      that memory labilization allows for the integration of relevant information in
      the established memory trace (memory updating). Memory labilization and
      reconsolidation do not necessarily occur when a memory is being reactivated, but
      only when there is something to be learned during memory retrieval (prediction
      error). Thus, updating of a fear memory trace should not occur under retrieval
      conditions in which the outcome is fully predictable (no prediction error). Here,
      we addressed this issue, using a human differential fear conditioning procedure,
      by eliminating the very possibility of reinforcement of the reminder cue. A
      previously established fear memory (picture-shock pairings) was reactivated with
      shock-electrodes attached (Propranolol group, n=18) or unattached (Propranolol No
      Shock Expectation group, n=19). We additionally tested a placebo-control group
      with the shock-electrodes attached (Placebo group, n=18). Reconsolidation was not
      triggered when nothing could be learned during the reminder trial, as
      noradrenergic blockade did not affect expression of the fear memory 24h later in
      the Propranolol No-Shock Expectation group. Only when the outcome of the
      retrieval cue was not fully predictable, propranolol, contrary to placebo,
      reduced the startle fear response and prevented the return of fear
      (reinstatement) the following day. In line with previous studies, skin
      conductance response and shock expectancies were not affected by propranolol.
      Remarkably, a double dissociation emerged between the emotional (startle
      response) and more cognitive expression (expectancies, SCR) of the fear memory.
      Our findings have important implications for reconsolidation blockade as
      treatment strategy for emotional disorders. First, fear reducing procedures that
      target the emotional component of fear memory do not necessarily affect the
      cognitive component and vice versa. Second, mere retrieval of the fear memory is
      not sufficient to induce its labilization and reconsolidation.

PMID- 22406659
TI  - Mice treated with a nontoxic dose of chlorpyrifos oxon have
      diethoxyphosphotyrosine labeled proteins in blood up to 4 days post exposure,
      detected by mass spectrometry.
AB  - Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)
      activity is an established biomarker of exposure to organophosphorus poisons
      (OP). Inhibition of activity is due to covalent binding of the OP to the active
      site serine. Mass spectrometry has made it possible to monitor OP exposure by
      analyzing OP adducts on tyrosine in proteins that have no active site serine. Our
      goal was to test the hypothesis that OP-tyrosine may serve as a biomarker of OP
      exposure in mice. A MALDI-TOF mass spectrometry strategy to analyze
      diethoxyphosphate-tyrosine of m/z 318 was developed. The adduct was synthesized
      by incubating l-tyrosine with chlorpyrifos oxon at pH 8.1. The adduct eluted from
      a reverse phase HPLC column with 22-23% acetonitrile. The fragmentation spectrum
      of the m/z 318 precursor ion confirmed its identity as diethoxyphosphate
      tyrosine. Diethoxyphosphate-tyrosine was isolated from chlorpyrifos oxon treated
      mouse albumin after digesting the protein with pronase. Mice (n=3 per group) were
      treated with a nontoxic dose of chlorpyrifos oxon (3 mg/kg) and a toxic dose (10
      mg/kg transdermally). The pronase digested plasma yielded diethoxyphosphate
      tyrosine up to 120 h after treatment with 3 mg/kg chlorpyrifos oxon and up to 144
      h after 10 mg/kg. In contrast plasma AChE activity returned to normal after 24-72
      h. In conclusion MALDI-TOF mass spectrometry can be used to diagnose exposure to
      chlorpyrifos oxon days after AChE inhibition assays are uninformative.

PMID- 22406660
TI  - Detection and resolution of vanishing optotype letters in central and peripheral
      vision.
AB  - Previous studies of peripheral vision have shown that detection acuity is
      superior to resolution acuity for gratings over a range of contrasts, which is
      attributed to different limiting mechanisms (contrast insufficiency and neural
      undersampling) for the two tasks. To extend the analysis to letters in a way that
      avoided luminance cues, we used "vanishing optotype" characters, conveying second
      order information, and constructed from tripole strokes having the same mean
      luminance as the surround. We measured the minimum letter size for detection and
      identification tasks for two different pairs of vanishing optotype characters (O
      vs. + and orthogonally oriented Landolt-C's) as a function of contrast in central
      and peripheral vision. Foveally there was no significant difference between
      detection acuity and resolution acuity for either pair of letters over a range of
      stimulus contrasts from 20% to 100%, indicating performance is contrast-limited
      for both tasks. The same result was obtained at 30 degrees  eccentricity in the
      peripheral field for the O vs. + letters, again indicating performance is
      contrast-limited for both tasks. However, resolution acuity for the Landolt-C
      letters was significantly worse than detection acuity in the periphery over the
      same range of contrasts, which suggests performance is limited by neural
      undersampling for these letters. All of our experimental results are explained by
      a model of neural sampling in which detection acuity is determined by the size of
      neural receptive fields relative to the dimensions of the tripole responsible for
      spatial contrast, whereas resolution acuity is determined by the spacing of
      receptive fields relative to the spacing between strokes responsible for letter
      form.

PMID- 22406661
TI  - Sound can enhance the suppression of visual target detection in apparent motion
      trajectory.
AB  - Detection performance is impaired for a visual target presented in an apparent
      motion (AM) trajectory, and this AM interference weakens when orientation
      information is inconsistent between the target and AM stimuli. These indicate
      that the target is perceptually suppressed by internal object representations of
      AM stimuli established along the AM trajectory. Here, we showed that transient
      sounds presented together with AM stimuli could enhance the magnitude of AM
      interference. Furthermore, this auditory effect attenuated when frequencies of
      the sounds were inconsistent during AM. We also confirmed that the sounds wholly
      elevated the magnitude of AM interference irrespective of the inconsistency in
      orientation information between the target and AM stimuli when the saliency of
      the sounds was maintained. These results suggest that sounds can contribute to
      the robust establishment and spatiotemporal maintenance of the internal object
      representation of an AM stimulus.

PMID- 22406662
TI  - Investigation of center-surround interaction in motion with reaction time for
      direction discrimination.
AB  - How motion onset asynchrony (MOA) alters the effects of stimulus size on reaction
      time (RT) for direction discrimination of a drifting grating was examined. MOA is
      a delay from the stimulus onset to the onset of motion. Without MOA, RTs were
      found to increase as the stimulus size was increased at high contrast, but
      decrease with it at low contrast or at high noise levels. With MOA, however, RTs
      did not increase as the stimulus size increased even at high contrast. These
      results suggest that sudden stimulus onset evokes the increase of RTs with the
      increase of stimulus size at high contrast. RTs for direction discrimination of a
      drifting Gabor patch (the target) surrounded by a different drifting or a static
      grating as well as RTs for the target that was not surrounded by an additional
      grating were measured. The RTs for the target moving in the same or opposite
      direction as the motion of the surrounding grating were larger than those for the
      target with the static grating or no additional grating at moderate or high
      contrast. There was no significant difference between the RTs for the target
      moving in the same direction as the surrounding grating and the RTs for the
      target moving in the opposite direction. At low contrast and without MOA,
      however, the RTs for the target moving in the same direction as the surrounding
      grating were larger than those for the target moving in the opposite direction.
      These results suggest surround suppression at low contrast under some conditions.
      They also suggest that the decrease of RTs for discriminating motion direction of
      a drifting single Gabor patch with the increase of stimulus size at low contrast
      does not necessarily mean the absence of surround suppression.

PMID- 22406663
TI  - Review of intrauterine adhesiolysis at the Aminu Kano Teaching Hospital, Kano,
      Nigeria.
AB  - BACKGROUND: Hysteroscopic adhesiolysis is shown to significantly improve the
      outcome of intrauterine adhesions (IUA). The Minimally Invasive Surgical Unit
      (MISU) of our Department recently acquired a hysteroscope which is being used for
      hysteroscopic adhesiolysis among others. MATERIALS AND METHODS: There were 57
      patients diagnosed to have IUA of which 54 case notes were available for
      analysis, giving a retrieval rate of 95%. The information extracted includes age,
      parity, and menstrual pattern, predisposing factors, treatment option, outcome,
      complications and the year of the procedure. The data extracted were analyzed
      using Epi info Version 3.4.1. Chi squared test (Fisher's exact test) was used to
      test for statistical difference in the outcome of the modalities of treatment. P
      value of less than 0.05 was considered significant. RESULTS: There were 57 cases
      of IUA out of 4160 gynecological patients seen, giving a prevalence of 14/1000.
      The mean age was 28.9 years (SD 4.5) and mean parity was 1.4 (SD 1.4). Etiologic
      factors include Dilatation and curettage (D and C) (33.3%), Caesarean section
      (C/S) (31.5%), manual removal of placenta and Pelvic Inflammatory Disease (PID)
      (7.4% each), and unexplained (3.7%). Mode of presentation was secondary
      amenorrhoea (50%), oligomenorrhoea (22.2%), and hypomenorrhoea (10%). As for the
      management, 68% had blind procedure while 25.9% had hysteroscopic procedure.
      Lippes loop was used in all except three patients who had pediatric Foleys
      catheter instead. Upon follow-up 59.3% resumed normal menses, 11.1% had
      oligomenorrhoea, hypomenorrhoea 13% and amenorrhoea 5.6%. There was no
      statistical difference in the outcome of treatment between hysteroscopic
      adhesiolysis and the blind procedure when return to normal menses is considered
      as the end point, OR=2.27, CI 0.45-12.65, Fisher exact test (one-tailed)
      P=0.2184818. CONCLUSION: There was no significant difference between the blind
      and hysteroscopic procedures. Dilatation and curettage was found to be the
      commonest cause of IUA.

PMID- 22406664
TI  - Commercial kidney transplantation: trends, outcomes and challenges-a single
      centre experience.
AB  - BACKGROUND/OBJECTIVE: Many experts believe that commercial organ transplants
      continue unabated despite international efforts to curb them. The aim was to
      determine the trends, outcomes and challenges of commercial living unrelated
      renal transplants (LURT) as seen in our institution. MATERIALS AND METHODS: A
      retrospective study of LURT patients on follow-up at our institution. The list of
      all LURT patients was obtained from our renal registry. Inclusion criteria for
      the study were 1) Presentation to our hospital within the first month post
      transplant; 2) Completion of one-year follow-up OR patient or allograft losses
      prior to completing one-year follow-up. SPSS 17.0 was used for data analysis.
      RESULTS: Forty-five patients satisfied the entry criteria; 33 males and 12
      females with age range 13-68 years, and mean +/- SD of 40 + 15 years. The
      majority (28) of the transplants were carried out in Pakistan, the remaining in
      Egypt, Philippines, and China. There has been a steady decline in the number of
      new patients with commercial transplants over a four-year period. Complications
      encountered included infections in 19 (42.2%) patients, biopsy-proven acute
      rejections in nine patients (20%), surgical complications in 10 patients (22.2%),
      post-transplant diabetes in seven (15.6%), delayed graft function in one (2.2%),
      and chronic allograft nephropathy in one (2.2%) patient. Patient survival at one
      year was 97.8% and allograft survival was 88.9%. CONCLUSIONS: Commercial kidney
      transplant is on the decline as seen in our center, likely as a result of
      international efforts to curb it, as well as due to a parallel increase in renal
      transplants in the country. One-year patient and allograft survivals are good but
      there is a relatively high rate of infections.

PMID- 22406665
TI  - Pattern of diabetic retinopathy in Kano, Nigeria.
AB  - BACKGROUND: The aim of the study is to determine the pattern of retinopathy seen
      in diabetic patients attending the outpatient clinic in Aminu Kano Teaching
      Hospital, Kano, Nigeria. MATERIALS AND METHODS: Consecutive patients who were
      attending the diabetic clinic and who consented were examined over a three-month
      period. Information obtained includes patient's bio data, type and duration of
      disease, and findings on eye examination. The fundus was examined with direct and
      indirect ophthalmoscopes, +90 D with slit lamp and fundal photography.
      Retinopathy was graded using the International Clinical Diabetic Retinopathy
      Disease Severity Scale (ICDRDSS). RESULTS: A total of 214 patients were examined
      during the study period. There were 88 males and 126 females (M: F = 1: 1.43).
      The mean age of the study population was 52.14 +/- 13.23 years. The mean age of
      patients without diabetic retinopathy (DR) was 49.14 +/- 13.17 years and the mean
      age of patients with DR was 58.51 +/- 10.94 years. Forty nine patients (23%) had
      insulin-dependent diabetes mellitus (IDDM) while 165 patients (77%) had non
      insulin dependent diabetes mellitus (NIDDM). There was statistically significant
      difference in presence of retinopathy in patients with IDDM compared to those
      with NIDDM [X(2) =29.77 {95% CI}, P=0.000]. DR was significantly more common in
      patients with disease duration of 15 years or more compared with those with
      disease duration of 14 years or less [X(2) = 65.85, {95% CI} P= 0.000]. Based on
      ICDRDSS scale, 136 patients (64%) had no retinopathy and 78 patients (36%) had
      retinopathy. Some patients were visually impaired and the cause of blindness was
      DR in 6 patients (2.8%). Cataract and glaucoma were the cause in 6 patients
      (2.8%). CONCLUSION: Diabetic retinopathy is common in our environment and is more
      frequent in IDDM and those with long disease duration. DR is a cause of visual
      disability although diabetic patients are not exempted from blindness from other
      eye diseases such as cataract and glaucoma. A screening program needs to be
      developed to facilitate early detection and prompt treatment.

PMID- 22406666
TI  - Trichiasis surgical coverage in three local government areas of Sokoto state,
      Nigeria.
AB  - BACKGROUND: Community-based lid surgery for trachomatous trichiasis (TT) is
      provided in 8 local government areas (LGAs) of Sokoto state since 2003 as part of
      a trachoma control programme. This study aims to assess the impact of community
      based lid surgery on the magnitude of TT in 3 LGAs of Sokoto state. MATERIALS AND
      METHODS: A population-based survey was conducted in persons aged 15 years and
      above. A stratified multistage cluster sampling with probability proportional to
      size was used. Trachoma was assessed using the WHO simplified grading system.
      RESULTS: Despite high (13%) refusals, 72% of the minimum sample size was
      examined. The prevalence of blindness ranged from 1.3% to 2.5% in the LGAs while
      the prevalence of TT in persons aged 15 years and above was 2% in the Silame,
      2.7% in the Wamakko and 5.6% in the Kware LGAs, respectively. The prevalence of
      TT in females 15 years and above was 1.1% in the Silame, 4% in the Wamakko and
      6.3% in the Kware LGAs, respectively. The trichiasis surgical coverage is 9.5% in
      the Kware and 12.5% in the other LGAs respectively. The minimum number of TT lid
      surgery required to achieve the elimination level is 873 in the Silame LGA, 2611
      in the Wamakko LGA and 4672 in the Kware LGA. CONCLUSION: The burden of TT is
      high in the study communities while the trichiasis surgical coverage is low.
      There is a need to strengthen the control programme to meet up with existing
      need.

PMID- 22406667
TI  - Left ventricular structure and function in black normotensive type 2 diabetes
      mellitus patients.
AB  - BACKGROUND: Relationship between type 2 DM and cardiovascular disease (CVD) is
      well known, with CVD being the most common cause of mortality in diabetics.
      Significant myocardial injury before overt CVD in DM can be identified early
      using echocardiography. This study therefore aimed at evaluating left ventricular
      structure and function of patients with type 2 DM. MATERIALS AND METHODS: One
      hundred and fifty adult type 2 DM patients were recruited with 150 age- and sex
      matched controls. Patients and subjects with systemic hypertension, pregnancy,
      sickle cell disease and structural heart disease were excluded from the study.
      Participants were evaluated clinically; had anthropometric parameters and
      electrocardiogram taken. Echocardiograms were obtained according to the American
      Society of Echocardiography (ASE) recommendations. RESULTS: Mean age of the
      patients (55.4 +/- 11.6 years) was similar to that of the control (54.2 +/- 9.6
      years) (P=0.348) and the duration of DM was 4.53 years. Left ventricular (LV)
      systolic function was normal in both groups but was higher in patients than
      controls (ejection fraction=70.3 +/- 10.7% and 64.4 +/- 9.4%, P =0.001
      respectively). The prevalence of LV diastolic dysfunction (LVDD) was 72% in the
      patients compared with 6% in controls (P=0.001). Patients' age, body weight,
      duration of DM, LV mass index and left atrial dimension were positive correlates
      of LVDD while patients' age, weight and left atrial dimension were independent
      predictors of LVDD. CONCLUSION: There is high prevalence of alterations in LV
      structure and function in normotensive type 2 DM; and there is a need for early
      intervention to prevent overt LV dysfunction.

PMID- 22406668
TI  - Ultrasound-guided wire localization of lesions detected on screening mammography
      in Osogbo, Nigeria and its impact on breast conservative surgery.
AB  - BACKGROUND: Wire localization for planned surgical treatment in the management of
      breast cancer is underutilized in our environment. The objective of this study is
      to assess the role of ultrasound-guided wire localization of breast masses
      detected on screening mammography and its impact on biopsy and breast
      conservative surgery in our environment. MATERIALS AND METHODS: A prospective
      study of 189 women who presented for screening mammography following a health
      campaign on breast cancer within a six-month period. Wire localization for
      mammographic detected lesions was done under ultrasound guidance. The lesions
      excised were sent for specimen radiography and histology. RESULTS: Ten women had
      wire localization of breast lesions and subsequent excision. Three lesions were
      on the right and 7 on the left; out of which 3 were malignant. The mean volume of
      excised tissue was 74.27 +/- 30.16 cm(3). CONCLUSION: Early detection of breast
      cancer is possible and practicable in our environment. Wire localization of
      detectable lesions on mammography will assist in better surgical management and
      improve prognosis.

PMID- 22406669
TI  - Gender differences in the variables of exercise treadmill test in type 2 diabetes
      mellitus.
AB  - BACKGROUND: Exercise capacity, like some other variables of exercise stress test,
      is a strong predictor of cardiovascular and overall mortality. Many confounding
      factors, including gender, have been found to affect exercise capacity. This
      study evaluated whether exercise capacity differs in age-matched type 2 diabetic
      Nigerian men and their women counterparts and the hemodynamic variables of
      exercise treadmill test that correlate with exercise capacity in them. MATERIALS
      AND METHODS: A total of 61 type 2 diabetics (male = 34; female = 27) aged 30 to
      60 years who were recruited through the Medical Out-patient Department of OAUTHC,
      Ile Ife, Nigeria, underwent symptom-limited maximal treadmill exercise using
      Bruce protocol. RESULT: Patients had comparable clinical and demographic
      patterns. There was no gender difference in the chronotropic response to
      exercise. Males had faster heart rate recovery (HRR) than females. Though both
      sexes had similar resting systolic blood pressure (SBP), males had significantly
      higher peak SBP than females (216.2 +/- 23.7 mmHg vs 203.3 +/- 21.7 mmHg; P =
      0.03). Exercise capacity was significantly higher in males (7.5 +/- 2.0 METs)
      than females (6.4 +/- 1.5 METs); P = 0.01. Significant correlates of exercise
      capacity in both sexes were fasting plasma glucose, resting diastolic blood
      pressure, Duke Treadmill Score, and HRR. Majority of the patients were in
      moderate DUKE risk subgroup and there was no statistically significant difference
      between males and females in this regard. CONCLUSION: Gender difference occurs in
      the exercise capacity of diabetic patients and the factors associated with this
      disparity may be related to gender differences in resting heart rate and HRR,
      both reflecting a withdrawal of vagal tone.

PMID- 22406670
TI  - Age at menarche among school girls in Sokoto, Northern Nigeria.
AB  - BACKGROUND/OBJECTIVES: Menarche, the first menstrual period, is influenced by
      many factors including socio-economic status and rural or urban dwelling. The
      aims of the study were to compare the age at menarche between rural and urban
      girls and evaluate the anthropometric indices at menarche. MATERIALS AND METHODS:
      A cross-sectional study of rural secondary school girls and urban school girls. A
      structured questionnaire was used to obtain information on their age at menarche
      and other relevant data. Their weights and heights were measured using
      computerized scales and calibrated walls. RESULTS: Two hundred and twenty eight
      (228) rural girls and four hundred and eighty (480) urban girls that had attained
      menarche within a year were studied. Mean age at menarche for all the girls was
      15.26 years. Mean menarcheal age for the rural and urban girls were 15.32 years
      and 15.20 years, respectively. Mean weight and height were 47.6 kg and 156.76 cm,
      respectively for the rural girls and 48.12 kg and 156.8 cm, respectively for the
      urban girls. There was no significance difference in age of menarche among the
      groups (P > 0.05). CONCLUSION: The mean age at menarche for the school girls is
      15.26 years. There was no difference in menarcheal age between the rural and
      urban school girls. Further longitudinal studies to compare rural school girls
      and urban school girls in private schools are required.

PMID- 22406671
TI  - Incidence of dog bite injuries and clinical rabies in a tertiary health care
      institution: a 10-year retrospective study.
AB  - BACKGROUND: It is widely recognized that rabies is grossly under-reported even
      though it is a notifiable disease and a lack of accurate figures has rendered
      rabies a low public health and veterinary priority. This study aimed at
      determining the incidence of dog bite injuries and clinical rabies in a tertiary
      health care centre. MATERIALS AND METHODS: Case records of patients managed at
      the accident and emergency unit of Ahmadu Bello University Teaching Hospital,
      Zaria, between June 2000 and May 2010 with diagnosis of dog bite and rabies were
      retrieved. Relevant clinical data were extracted using a structured questionnaire
      designed for the study. RESULTS: Eighty-one persons out of 24,683 consultations
      in the accident and emergency unit presented with dog bite injuries with two
      clinical cases of human rabies. Mean age of victims of dog bite injuries was 21.1
      +/- 14.3 years and the majority (55.6%) were children. Males were more affected
      than females with a male:female ratio of 4.8:1, lower limb/buttock injuries were
      significantly higher in children than adults, but the adults sustained
      significantly more severe (type III) injury. The majority of dog bite injuries
      were washed with soap and irrigated with water or saline and 87.7% of the victim
      of dog bite received postexposure anti-rabies vaccine. CONCLUSION: Hospital
      incidence of dog bite injuries was low, but the use of postexposure prophylaxis
      was high.

PMID- 22406672
TI  - Bilateral tubal ectopic pregnancies: a report of two cases.
AB  - Bilateral tubal ectopic pregnancies are rare occurrences. Two recently managed
      cases are discussed. The first was a single, sexually active 23-year-old
      nullipara with family history of twinning who presented with eight weeks
      amenorrhea, positive pregnancy test, lower abdominal discomfort and other
      clinical and ultrasound findings suggestive of unruptured left tubal pregnancy.
      Intra-operatively, unruptured bilateral tubal pregnancies were found and
      bilateral salpingotomy performed with uneventful recovery. Histology of the
      specimens confirmed the intra-operative diagnosis. She was appropriately
      counseled. Case 2, a 30-year-old multiparous housewife who had been on clomid for
      secondary infertility, presented with signs and symptoms of ruptured tubal
      ectopic. Intra-operatively, ruptured left and unruptured right tubal pregnancies
      were found and salpingectomy and salpingotomy were done respectively, with
      uneventful recovery. The diagnosis was also confirmed histologically and
      counseling given as in case 1. Bilateral tubal ectopic pregnancies appear to be
      increasing with twin proneness and use of fertility drugs as risk factors.
      Whether spontaneous or induced, the hallmarks of good management include early
      presentation, high index of suspicion, meticulous ultrasound scanning, good case
      selection, judicious intra-operative inspection of the contralateral tube,
      histology of specimens and appropriate patient counseling.

PMID- 22406673
TI  - Arrow injuries to the eye.
AB  - Two male siblings aged 10 and 17 years, respectively, presented to our hospital
      with two days history of being shot in the right eyes with arrows. The patients
      presented with severe pains, bleeding, swelling, discharge and loss of vision.
      There was positive history of application of traditional eye medicine and an
      unsuccessful attempt was made to remove the arrows. Both patients presented with
      panophthalmitis. X-rays of the orbits and para nasal sinuses indicated the tip of
      the arrow was lodged to the apex of the orbit in the younger patient, and the
      arrow vertically traverses the eye/ orbit and lodged in the roof of the maxillary
      sinus in the other patient with fluid level in the lower third of the sinus. The
      patients were placed on broad-spectrum systemic antibiotics, had base line
      investigations and prepared for exploration. The patients had evisceration with
      removal of the arrows.

PMID- 22406674
TI  - Chronic kidney disease in sub-Saharan Africa: hypothesis for research demand.

PMID- 22406675
TI  - Giant pulmonary hydatid cyst mimicking elevated diaphragm: a diagnostic dilemma.

PMID- 22406676
TI  - Allosteric modulation balances thermodynamic stability and restores function of
      DeltaF508 CFTR.
AB  - Most cystic fibrosis is caused by a deletion of a single residue (F508) in CFTR
      (cystic fibrosis transmembrane conductance regulator) that disrupts the folding
      and biosynthetic maturation of the ion channel protein. Progress towards
      understanding the underlying mechanisms and overcoming the defect remains
      incomplete. Here, we show that the thermal instability of human DeltaF508 CFTR
      channel activity evident in both cell-attached membrane patches and planar
      phospholipid bilayers is not observed in corresponding mutant CFTRs of several
      non-mammalian species. These more stable orthologs are distinguished from their
      mammalian counterparts by the substitution of proline residues at several key
      dynamic locations in first N-terminal nucleotide-binding domain (NBD1), including
      the structurally diverse region, the gamma-phosphate switch loop, and the
      regulatory insertion. Molecular dynamics analyses revealed that addition of the
      prolines could reduce flexibility at these locations and increase the
      temperatures of unfolding transitions of DeltaF508 NBD1 to that of the wild type.
      Introduction of these prolines experimentally into full-length human DeltaF508
      CFTR together with the already recognized I539T suppressor mutation, also in the
      structurally diverse region, restored channel function and thermodynamic
      stability as well as its trafficking to and lifetime at the cell surface. Thus,
      while cellular manipulations that circumvent its culling by quality control
      systems leave DeltaF508 CFTR dysfunctional at physiological temperature,
      restoration of the delicate balance between the dynamic protein's inherent
      stability and channel activity returns a near-normal state.

PMID- 22406678
TI  - Alternariol induces DNA polymerase beta expression through the PKA-CREB signaling
      pathway.
AB  - Alternariol (AOH) is a mycotoxin of Alternaria alternata and can cause DNA damage
      and gene mutations. Low-dose and long-term treatment with AOH has been linked
      with incidence of esophageal carcinoma. DNA polymerase beta (polbeta) is a key
      enzyme in DNA base excision repair (BER). When it is overexpressed or mutated in
      cells, DNA polbeta can cause genetic instability. Elevated DNA polbeta has also
      been reported in several human cancers. Here, we report that AOH at 2, 10, 20 uM
      induces DNA polbeta expression. In the process, protein kinase A (PKA) catalytic
      subunit activation, nuclear translocation and cAMP response element binding
      protein (CREB) phosphorylation are involved. AOH also increased CREB binding to
      the cAMP response element (CRE) consensus motif, which is present in the DNA
      polbeta gene promoter. The PKA inhibitor H89 was able to block AOH-induced PKA
      CREB activation, CREB DNA binding activity and decrease DNA polbeta expression.
      Our results suggest that AOH can upregulate DNA polbeta expression through the
      PKA-CREB signal transduction pathway.

PMID- 22406677
TI  - CC2D1A is a regulator of ESCRT-III CHMP4B.
AB  - Endosomal sorting complexes required for transport (ESCRTs) regulate diverse
      processes ranging from receptor sorting at endosomes to distinct steps in cell
      division and budding of some enveloped viruses. Common to all processes is the
      membrane recruitment of ESCRT-III that leads to membrane fission. Here, we show
      that CC2D1A is a novel regulator of ESCRT-III CHMP4B function. We demonstrate
      that CHMP4B interacts directly with CC2D1A and CC2D1B with nanomolar affinity by
      forming a 1:1 complex. Deletion mapping revealed a minimal CC2D1A-CHMP4B binding
      construct, which includes a short linear sequence within the third DM14 domain of
      CC2D1A. The CC2D1A binding site on CHMP4B was mapped to the N-terminal helical
      hairpin. Based on a crystal structure of the CHMP4B helical hairpin, two surface
      patches were identified that interfere with CC2D1A interaction as determined by
      surface plasmon resonance. Introducing these mutations into a C-terminal
      truncation of CHMP4B that exerts a potent dominant negative effect on human
      immunodeficiency virus type 1 budding revealed that one of the mutants lost this
      effect completely. This suggests that the identified CC2D1A binding surface might
      be required for CHMP4B polymerization, which is consistent with the finding that
      CC2D1A binding to CHMP4B prevents CHMP4B polymerization in vitro. Thus, CC2D1A
      might act as a negative regulator of CHMP4B function.

PMID- 22406680
TI  - [Clinical economics: a concept to optimize healthcare services].
AB  - Clinical economics strives to support healthcare decisions by economic
      considerations. Making economic decisions does not mean saving costs but rather
      comparing the gained added value with the burden which has to be accepted. The
      necessary rules are offered in various disciplines, such as economy, epidemiology
      and ethics. Medical doctors have recognized these rules but are not applying them
      in daily clinical practice. This lacking orientation leads to preventable errors.
      Examples of these errors are shown for diagnosis, screening, prognosis and
      therapy. As these errors can be prevented by application of clinical economic
      principles the possible consequences for optimization of healthcare are
      discussed.

PMID- 22406679
TI  - [Resection of Klatskin tumors].
AB  - Curative treatment of Klatskin tumors by radical surgical procedures with
      surgical preparation distant to the tumor region results in 5-year survival rates
      of 30-50%. This requires mandatory en bloc liver resection and resection of the
      extrahepatic bile duct often together with vascular resection. Nevertheless, the
      ideal safety margin of 0.5-1 cm remote from the macroscopic tumor extensions
      cannot be achieved in all cases. Based on hilar anatomy the probability of an
      adequate safety margin is higher using extended right hemihepatectomy together
      with portal vein resection compared to left hemihepatectomy. However, due to
      severe atrophy of the left liver lobe solely left-sided hepatectomy is feasible
      in some patients. In cases of eligibility for both procedures right
      hemihepatectomy is preferentially used due to the higher oncological radicality
      if sufficient liver function is present. Postoperative hepatic insufficiency and
      bile leakage after demanding biliary reconstruction, often with several small
      orifices, contribute to the postoperative complication rate of this complex
      surgical disease pattern.

PMID- 22406681
TI  - [Fractures of the humerus head].
AB  - Fractures of the proximal humerus are commonly seen especially in the elderly
      population. High-energy trauma in young people can be distinguished from low
      energy trauma in the elderly resulting from falls of a low height which are
      typically characterized by osteoporosis. A precise analysis of fractures is
      essential for a good understanding of the fracture and an individual therapy for
      which the LEGO-Codman classification provided by Hertel is recommended.
      Nonsurgical therapy is commonly performed and widely accepted not only for simple
      fractures. For osteosynthesis angular stable implants became the gold standard
      but are frequently associated with a high rate of complications some of which can
      be lowered by an improved surgical technique. Even today varus dislocated
      fractures are challenging, especially in combination with destruction of the
      medial column. In those cases where stable osteosynthesis can no longer be
      achieved arthroplasty is indicated. The clinical results of anatomic fracture
      arthroplasty are strongly related with correct ingrowth of the tuberosities.
      Reverse fracture arthroplasty may be considered but indications should be
      interpreted with caution and preferably used in patients older than 75 years.

PMID- 22406682
TI  - Effectors of tridimensional cell morphogenesis and their evolution.
AB  - One of the most challenging problems in biology resides in unraveling the
      molecular mechanisms, hardwired in the genome, that define and regulate the
      multiscale tridimensional organization of organs, tissues and individual cells.
      While works in cultured cells have revealed the importance of cytoskeletal
      networks for cell architecture, in vivo models are now required to explore how
      such a variety in cell shape is produced during development, in interaction with
      neighboring cells and tissues. The genetic analysis of epidermis development in
      Drosophila has provided an unbiased way to identify mechanisms remodeling the
      shape of epidermal cells, to form apical trichomes during terminal
      differentiation. Since hearing in vertebrates relies on apical cell extensions in
      sensory cells of the cochlea, called stereocilia, the mapping of human genes
      causing hereditary deafness has independently identified several factors required
      for this peculiar tridimensional organization. In this review, we summarized
      recent results obtained toward the identification of genes involved in these
      localized changes in cell shape and discuss their evolution throughout
      developmental processes and species.

PMID- 22406683
TI  - New aspects of the Warburg effect in cancer cell biology.
AB  - Altered cellular metabolism is a defining feature of cancer [1]. The best studied
      metabolic phenotype of cancer is aerobic glycolysis--also known as the Warburg
      effect--characterized by increased metabolism of glucose to lactate in the
      presence of sufficient oxygen. Interest in the Warburg effect has escalated in
      recent years due to the proven utility of FDG-PET for imaging tumors in cancer
      patients and growing evidence that mutations in oncogenes and tumor suppressor
      genes directly impact metabolism. The goals of this review are to provide an
      organized snapshot of the current understanding of regulatory mechanisms
      important for Warburg effect and its role in tumor biology. Since several reviews
      have covered aspects of this topic in recent years, we focus on newest
      contributions to the field and reference other reviews where appropriate.

PMID- 22406684
TI  - Aqueous room temperature synthesis of cobalt and zinc sodalite zeolitic
      imidizolate frameworks.
AB  - Sodalite zeolitic imidazolate frameworks containing Co (ZIF-67) and Zn (ZIF-8)
      were synthesized at room temperature under aqueous conditions in 10 min. A
      trialkylamine deprotonated the 2-methylimidazole ligand and nucleated the
      frameworks. Furthermore, the ligand acted as a structure directing agent in place
      of an organic solvent.

PMID- 22406685
TI  - Isolated frontopolar cortex lesion:  a case study.
AB  - BACKGROUND: The frontopolar cortex has been proposed to mediate prospective
      memory functioning, multitasking, relational integration, processing of internal
      states, and self-referential evaluation. These theories are based primarily on
      functional activation studies. The few lesion models reported have not been
      restricted to the frontopolar cortex. AIM: We used neuropsychological tests and
      neuroimaging to study an otherwise healthy woman with an isolated hemorrhagic
      infarct in the frontopolar cortex. METHODS: In addition to a standard stroke work
      up, the patient had cognitive psychometric tests reflecting the theoretical
      frontal functions of initiation, monitoring, inhibition, and working memory, as
      well as a test for emotional intelligence. RESULTS: The midline frontopolar
      intracerebral hemorrhage was isolated, free of other pathology, and almost solely
      within Brodmann area 10. The only psychometric abnormalities concerned awareness
      of, understanding, and expressing emotions. CONCLUSIONS: This report may be the
      first of an isolated bilateral lesion of the frontopolar cortex, Brodmann area
      10, with uniformly normal frontal lobe tests except for 2 abnormal findings of
      emotional intelligence. This lesion study supports the proposal that the medial
      frontopolar cortex is necessary for emotional processing of internal states.

PMID- 22406687
TI  - A caged cyanide.
AB  - A photoactivatable caged cyanide, 1-(2-nitrophenyl)ethyl (NPE) cyanide, was
      synthesized, which upon irradiation in the near UV releases cyanide. It is
      demonstrated that the compound can be used to induce formation of the Fe(III)-CN(
      ) complex in the heme protein nitrophorin 4 from Rhodnius prolixus.

PMID- 22406686
TI  - Molecular mechanisms that control the expression and activity of Bcl-6 in TH1
      cells to regulate flexibility with a TFH-like gene profile.
AB  - The transcription factors T-bet and Bcl-6 are required for the establishment of a
      T helper type 1 cell (T(H)1 cell) and follicular helper T cell (T(FH) cell) gene
      expression profile, respectively. Here we found that high concentrations of
      interleukin 2 (IL-2) inhibited Bcl-6 expression in polarized T(H)1 cells.
      Mechanistically, the low concentrations of Bcl-6 normally found in effector T(H)1
      cells did not repress its target genes because a T-bet-Bcl-6 complex masked the
      Bcl-6 DNA-binding domain. T(H)1 cells increased their Bcl-6/T-bet ratio in
      response to limiting IL-2 conditions, which allowed excess Bcl-6 to repress its
      direct target Prdm1 (which encodes the transcriptional repressor Blimp-1). The
      Bcl-6-dependent repression of Blimp-1 effectively induced a partial T(FH) profile
      because Blimp-1 directly repressed a subset of T(FH) signature genes, including
      Cxcr5. Thus, IL-2-signaling regulates the Bcl-6-Blimp-1 axis in T(H)1 cells to
      maintain flexibility with a T(FH) cell-like gene profile.

PMID- 22406688
TI  - Actinomyces meyeri infection: case report and review of the literature.
AB  - Actinomyces meyeri is an uncommon cause of actinomycosis. We present a patient
      with pneumonia and empyema due to A. meyeri. The patient underwent open
      thoracotomy with decortication and was discharged home on a twelve-month course
      of oral penicillin. Review of the English literature revealed thirty-two cases of
      infection due to A. meyeri. The majority of patients were male, and a significant
      number had poor dental hygiene and a history of alcoholism. More than other
      Actinomyces species, A. meyeri causes pulmonary infection and has a predilection
      for dissemination. Prognosis is favorable with prolonged penicillin therapy
      combined with surgical debridement, if needed.

PMID- 22406689
TI  - Kidney transplantation in an elite HIV controller: limited impact of
      immunosuppressive therapy on viro-immunological status.

PMID- 22406690
TI  - DNA biosensors that reason.
AB  - Despite the many designs of devices operating with the DNA strand displacement,
      surprisingly none is explicitly devoted to the implementation of logical
      deductions. The present article introduces a new model of biosensor device that
      uses nucleic acid strands to encode simple rules such as "IF DNA_strand(1) is
      present THEN disease(A)" or "IF DNA_strand(1) AND DNA_strand(2) are present THEN
      disease(B)". Taking advantage of the strand displacement operation, our model
      makes these simple rules interact with input signals (either DNA or any type of
      RNA) to generate an output signal (in the form of nucleotide strands). This
      output signal represents a diagnosis, which either can be measured using FRET
      techniques, cascaded as the input of another logical deduction with different
      rules, or even be a drug that is administered in response to a set of symptoms.
      The encoding introduces an implicit error cancellation mechanism, which increases
      the system scalability enabling longer inference cascades with a bounded and
      controllable signal-noise relation. It also allows the same rule to be used in
      forward inference or backward inference, providing the option of validly
      outputting negated propositions (e.g. "diagnosis A excluded"). The models
      presented in this paper can be used to implement smart logical DNA devices that
      perform genetic diagnosis in vitro.

PMID- 22406691
TI  - Different patterns of abnormal gamma oscillatory activity in unipolar and bipolar
      disorder patients during an implicit emotion task.
AB  - This study investigates the distinct patterns of local and long-range gamma
      oscillations between patients with bipolar disorder (BD) and major depressive
      disorder (MDD). Twenty BD patients, twenty MDD patients, and twenty normal
      controls participated in this study. For each participant, the event-related
      magnetoencephalographic responses while performing an implicit emotional task
      were recorded and processed with time-frequency analysis. Compared to normal
      controls, the BD patients exhibited the gamma power decease at the right frontal
      and prefrontal regions and yet gamma power increase at the right posterior
      temporal region. The abnormal long-range gamma oscillation between the right
      frontal and parietal-occipital region was also found. These results indicate that
      the BD patients may have hyperactivity in perceptual binding of emotional
      features and tend to be oversensitive to facial features. On the other hand, MDD
      patients displayed increased early gamma activity at the left anterior temporal
      region, which may imply their hyperactivated binding process of emotional
      features at corticolimbic regions. The distinct alterations of gamma patterns
      between the BD and MDD patients implicate that their impairments of binding
      processes are located at different regions. Gamma activity in the parietal and
      left posterior temporal regions may be a potential index to differentiate BD
      patients from MDD patients.

PMID- 22406692
TI  - Age-related loss in attention-based modulation of tactile stimuli at early stages
      of somatosensory processing.
AB  - Normal aging has been linked to impairments in gating of irrelevant sensory
      information and neural markers of diminished cognitive processing. Whilst much of
      the research in this area has focussed on visual and auditory modalities it is
      unclear to what degree these findings apply to somatosensation. Therefore we
      investigated how age impacts early event-related potentials (ERPs) arising from
      relevant or irrelevant vibrotactile stimuli to the fingertips. Specifically, we
      hypothesised that older adults would demonstrate reduced attention-based
      modulation of tactile ERPs generated at early stages of cortical somatosensory
      processing. In accord with previous research we also expected to observe
      diminished P300 responses to attended targets and behavioural deficits.
      Participants received vibrotactile stimulation to the second and fifth digit on
      the left hand and reported target stimuli on one digit only (as instructed) with
      comparisons between two age groups: (1) Young adults (age range 20-39) and (2)
      Older adults (age range 62-89). ERP amplitudes for the P50, N70, P100, N140 and
      long latency positivity (LLP) were quantified for attended and non-attended
      trials at several electrodes (C4, CP4, CP3 and FC4). The P300 in response to
      attended target stimuli was measured at CPZ. There was no effect of attention on
      the P50 and N70 however the P100, N140 and LLP were modulated with attention. In
      both age groups the P100 and LLP were more positive during trials where the
      stimuli were attended to, whilst the N140 was enhanced for non-attended stimuli.
      Comparisons between groups revealed a reduction in P100 attention-based
      modulation for the older adults versus the young adults. This effect was due to a
      loss of suppression of the non-attended stimuli in older subjects. Moreover, the
      P300 was both slower and reduced in peak amplitude for older subjects in response
      to attended targets. Finally, older adults demonstrated impaired performance in
      terms of both reduced target detection accuracy and in reporting more false
      positives. Overall, present results reveal a deficit in suppressing irrelevant
      tactile information during an attention-demanding task which possibly relates to
      reduced markers of performance. Such a loss of inhibitory function is consistent
      with age-related change associated with a decline in executive control via
      prefrontal regions.

PMID- 22406693
TI  - Future thinking in Parkinson's disease: an executive function?
AB  - Contrary to what was originally thought (Hassabis, Kumaran, Vann, & Maguire,
      2007) recent data have shown that imagining the future is not entirely dependent
      on the hippocampus (Squire et al., 2010) and neuroimaging studies have
      demonstrated a frontopolar activation during future thinking tasks (Okuda et al.,
      2003). The present study investigated whether the performance of people with
      Parkinson's disease (PD) on future simulation tasks was dependent on memory or
      executive control. Thirty-one PD patients, asked to imagine possible future
      scenarios, generated fewer future episodic details than matched controls. The
      seven patients who clearly performed below the range of controls in future
      thinking, were also significantly poorer on the Frontal Assessment Battery (FAB),
      a battery assessing executive control, but showed no deficits in immediate or
      delayed memory tests. These results suggest that poor performance in the future
      thinking task is associated with poor executive control and less so with memory
      impairment. Flexible searching activities of past details might be crucial
      capacities for envisaging one's own future.

PMID- 22406694
TI  - Emotional processing and its impact on unilateral neglect and extinction.
AB  - Unilateral spatial neglect is a neurological disorder characterized by impaired
      orienting of attention to stimuli located in the contralesional space, typically
      following right-hemisphere damage. Neuropsychological investigations in the past
      two decades have demonstrated that neglect is caused by deficits affecting a
      widespread cortico-subcortical fronto-parietal network controlling spatial
      attention, but usually sparing early sensory pathways. As a consequence, certain
      residual abilities in sensory processing remain intact and still take place for
      stimuli in the neglected space, such as the extraction and organization of
      coherent or meaningful object features. Moreover, these residual abilities can
      alleviate inattention symptoms when contralesional stimuli are perceptually or
      biologically salient. Here we review recent studies suggesting that the emotional
      content of stimuli may also be processed despite impaired attention towards
      contralesional space, and that such processing may act to enhance attention and
      partly reduce neglect for these stimuli, relative to similar but emotionally
      neutral stimuli. For example, faces with emotional expressions, voices with
      emotional prosody, as well as pictures of scenes or even spiders have been found
      to be less severely extinguished from awareness in conditions of bilateral
      stimulations, and/or lead to fewer omissions in search tasks with multiple
      distracters. Gaze cues and reward learning might also produce similar effects.
      Altogether, these findings suggest that emotionally significant information is
      not only extracted from stimuli at neglected locations through spared pathways,
      but can also induce emotional biases in attention that partly counteract the
      abnormal spatial biases caused by fronto-parietal damage. We discuss results from
      neuropsychology and neuroimaging research suggesting that specific mechanisms for
      emotional attention might exist, centered on the amygdala and other limbic
      regions, and that these mechanisms can operate partly independent from other
      circuits controlling spatial and object-based attention. Although we are only
      beginning to understand these interactive effects of emotion and attention and to
      identify their neuroanatomical substrates, we believe that a deeper knowledge of
      such mechanisms and their conditions of optimal operation will help develop or
      improve therapeutic strategies in neglect patients.

PMID- 22406695
TI  - Metrics and the effective computational scientist: process, quality and
      communication.
AB  - Recent treatments of computational knowledge worker productivity have focused
      upon the value the discipline brings to drug discovery using positive anecdotes.
      While this big picture approach provides important validation of the
      contributions of these knowledge workers, the impact accounts do not provide the
      granular detail that can help individuals and teams perform better. I suggest
      balancing the impact-focus with quantitative measures that can inform the
      development of scientists. Measuring the quality of work, analyzing and improving
      processes, and the critical evaluation of communication can provide immediate
      performance feedback. The introduction of quantitative measures can complement
      the longer term reporting of impacts on drug discovery. These metric data can
      document effectiveness trends and can provide a stronger foundation for the
      impact dialogue.

PMID- 22406696
TI  - Targeting endothelin receptors for pharmacotherapy of ischemic stroke: current
      scenario and future perspectives.
AB  - Increased expression of endothelin (ET) peptide and its receptors following
      ischemic stroke is found to regulate many critical aspects of stroke
      pathophysiology. Many attempts have been made to target ET receptors in various
      animal models of stroke, but it is very difficult to draw a definite line of
      conclusion, because these studies differ in many aspects, such as animal model,
      treatment schedule, parameters and techniques used for assessing these
      parameters. A meta-analysis of all studies showed a significant reduction in the
      lesion volume and improvement in functional outcome in focal cerebral ischemia.
      ET(A) receptor antagonists appear to offer an essential advantage of multiple
      neuroprotective mechanisms, including prevention of blood-brain barrier
      disruption and leukocyte infiltration.

PMID- 22406697
TI  - Alcohol pharmacokinetics and risk-taking behaviour following exercise-induced
      dehydration.
AB  - This study investigated the influence of exercise-induced dehydration on alcohol
      pharmacokinetics, subjective ratings of impairment, and risk-taking behaviours.
      Twelve male volunteers participated in 3 experimental trials completed in a
      randomised cross over design separated by at least 7 days. In one trial,
      participants exercised to cause dehydration of ~2.5% body weight loss. For the
      other trials, participants were required to be in a rested and euhydrated state.
      A set volume of alcohol was then consumed in each trial and participants were
      monitored over a 4h period. Blood (BAC) and breath (BrAC) alcohol samples were
      collected throughout and analysed to calculate pharmacokinetic variables
      associated with the blood alcohol curve. Total urine production, estimates of
      BrAC, and subjective ratings of intoxication and impairment were also recorded
      throughout each trial. No difference was found in the pharmacokinetics of alcohol
      between any of the trial conditions. BrACs were higher than BACs for 2h following
      alcohol consumption, but lower at measures taken 3 and 4 h post ingestion.
      Participants' ratings of confusion and intoxication were significantly lower, and
      they were more willing to drive in the dehydration trial compared with one of the
      euhydration trials. These findings suggest that dehydration or other
      physiological changes associated with exercise may have an ability to influence
      the subjective effects of alcohol and increase the likelihood of risk-taking
      behaviours such as drink-driving. However, further research is required to
      examine the effects of alcohol under conditions of exercise-induced fluid loss in
      order to clarify these findings.

PMID- 22406698
TI  - Prenatally diagnosed coarctation: a more sinister disease?
AB  - Prenatal diagnosis of coarctation may improve survival, but little is known
      regarding its association with severity of left heart hypoplasia and surgical
      outcome. This study compared echocardiographic measurements of left heart
      structures, surgical strategies, and postoperative outcomes between neonates with
      a prenatal diagnosis of coarctation and those with a postnatal diagnosis. All the
      neonates who underwent coarctation repair during 2006-2010 were reviewed. The
      neonates with complex congenital heart disease or an unrestrictive ventricular
      septal defect requiring cardiopulmonary bypass (CPB) for closure were excluded
      from the study. Based on the time of diagnosis, the subjects were divided into
      the following three groups: group 1 (prenatal diagnosis), group 2 (diagnosis at 0
      7 days), and group 3 (diagnosis at 8-28 days). The study population consisted of
      46 neonates: 14 in group 1, 14 in group 2, and 18 in group 3. Compared with group
      3, group 1 had a smaller left ventricular volume index, lower mitral and aortic
      valve diameter z-scores, and lower transverse arch z-scores. Compared with group
      2, group 1 had smaller aortic valve z-scores but otherwise had similar
      measurements. At repair, 64 % of the neonates in group 1 required CPB versus 29 %
      in group 2 (p = 0.12) and 22 % in group 3 (p = 0.03). All the neonates underwent
      biventricular repair, with no surgical mortality. Group 1 had a hospital stay of
      13.4 +/- 10.8 versus 7.5 +/- 4.2 days in group 2 (p = 0.06) and 7.3 +/- 4.5 days
      in group 3 (p = 0.03). The neonates with prenatally diagnosed coarctation had
      smaller left heart structures than the neonates with coarctation diagnosed after
      the first week of age, were more likely to require extensive arch reconstruction
      under CPB, and had longer hospital stays.

PMID- 22406700
TI  - Promoting ISDR to divisional status in IADR.

PMID- 22406701
TI  - Defining the role of Oral Physicians.

PMID- 22406702
TI  - Comparison of apical sealing and periapical extrusion of the ThermaFil obturation
      technique with and without MTA as an apical barrier: an in vitro study.
AB  - AIM: The aim of the study was to compare the conventional ThermaFil obturation
      technique and ThermaFil obturation with mineral trioxide aggregate (MTA) as an
      apical barrier, with regard to apical sealing and extrusion. MATERIALS AND
      METHODS: Twenty extracted human canines were instrumented using a crown-down
      technique and divided into two groups. The experimental group was obturated using
      ThermaFil obturation with MTA as an apical barrier and the control group was
      obturated using the conventional ThermaFil obturation technique. AH Plus sealer
      was used in both the groups. Apical extrusion was recorded. Teeth of both the
      groups were coated with nail polish, except for the apical 3 mm. After 24 h, they
      were suspended in black India ink for 48 h. Canines were decalcified, rendered
      transparent, and linear dye penetration was measured under *40 stereomicroscope.
      RESULTS: There was a significant extrusion noticed in conventional ThermaFil
      obturation technique. Frequency of extrusion of sealer and/or gutta-percha was
      supposed to be evaluated using chi2 test, but since the values of the samples of
      ThermaFil plus MTA group were zero, statistical analysis could not be conducted,
      whereas linear dye leakage was calculated with Mann-Whitney U test because the
      distribution was abnormal. CONCLUSION: Although ThermaFil plus MTA group showed
      microleakage, extrusion of sealer and the core material was prevented in
      comparison with conventional ThermaFil obturation technique. It is advantageous
      to use MTA as an apical plug as there is no fear of apical extrusion and the root
      canal system can then be packed three dimensionally against this barrier using
      any thermoplasticized gutta-percha obturation technique.

PMID- 22406703
TI  - Maturation of permanent teeth in different facial types: a comparative study.
AB  - BACKGROUND: Accurate diagnosis of dental maturation help in diagnosis, treatment
      planning, and timing in orthodontics and dentofacial orthopedics. AIM AND
      OBJECTIVE: The present study is undertaken to compare and correlate chronological
      age and dental age of patients with average, vertical, and horizontal facial
      types, and to find out any sex difference in dental age in different growth
      patterns and to evaluated the reliability of Willem's method in Indian
      population. MATERIALS AND METHODS: Subjects in the age group of 8-10 years were
      screened from Out Patients Department of Orthodontics and Dentofacial Orthopedics
      and from the various school of the City, were subjected to cephalometric
      radiography and orthopentomograms. Angular and linear measurements used included;
      SN Go-Gn angle, J.R. (Jarabak ratio) and LAFH (lower anterior facial height), to
      group total sample of 150 children. Group 1 (average grower), Group 2 (vertical
      grower), and Group 3 (horizontal grower). Then dental age for each child in
      different group was calculated from OPG of each subject and compared with
      chronological age using Student t-test. RESULTS: The results suggest a difference
      in dental age in subject with vertical and horizontal growers. Vertical grower
      showed earlier maturation compared to horizontal growth patterns. There was
      insignificant difference present when vertical grower and horizontal grower were
      compared with average growth pattern. Insignificant difference was found in
      dental age between males and females when compared to same growth pattern.
      CONCLUSION: Subjects with vertical growth pattern matured early than having the
      horizontal growth pattern in the same chronological age.

PMID- 22406704
TI  - Complications of exodontia: a retrospective study.
AB  - PURPOSE: The purpose of this study was to analyze the incidence of various
      complications following routine exodontia performed using fixed protocols.
      MATERIALS AND METHODS: A total of 22,330 extractions carried out in 14,975
      patients, aged between 14 and 82 years, who reported to the Department of Oral
      and Maxillofacial Surgery at Padmashree Dr. D. Y. Patil Dental College and
      Hospital, Nerul, Navi Mumbai, were evaluated for various complications. RESULTS:
      The most common complications encountered were tooth fracture, trismus, fracture
      of cortical plates and dry socket. Wound dehiscence, postoperative pain and
      hemorrhage were encountered less frequently. Luxation of adjacent teeth, fracture
      of maxillary tuberosity, and displacement of tooth into adjacent tissue spaces
      were rare complications. CONCLUSION: The practice of exodontia inevitably results
      in complications from time to time. It is imperative for the clinician to
      recognize impending complications and manage them accordingly.

PMID- 22406705
TI  - Lycopene in the management of oral lichen planus: a placebo-controlled study.
AB  - CONTEXT: Oxidative stress has been implicated in the pathogenesis of lichen
      planus, and a lower level of lycopene has been reported in erosive and atrophic
      oral lichen planus (OLP) patients. However, its efficacy in the management of OLP
      has not been reported. AIM: This study was designed to assess the efficacy of
      systemic lycopene in the management of OLP. SETTINGS AND DESIGN: This
      prospective, randomized, double-blind, placebo-controlled study was done in the
      Oral Medicine Department of a postgraduate teaching dental hospital in India.
      MATERIALS AND METHODS: Thirty symptomatic OLP patients, randomly divided into two
      groups of 15 each, were administered lycopene 8 mg/day and an identical placebo,
      respectively, for 8 consecutive weeks. Burning sensation using visual analogue
      scale and overall treatment response using Tel Aviv-San Francisco scale were
      recorded at every visit. The data obtained were analyzed statistically using
      Wilcoxon Rank test, Mann-Whitney and Fischer's Exact test. RESULTS: A higher
      (84%) reduction in burning sensation was seen in lycopene than in the placebo
      group (67%). All 15 (100%) patients in the lycopene group showed 50% or more
      benefit and 11 (73.3%) patients showed 70-100% benefit, while this number was
      only 10 and 4 (26.7%), respectively, in the placebo group. CONCLUSION: Lycopene
      was very effective in the management of OLP, and oxidative stress may have a role
      in disease pathogenesis.

PMID- 22406706
TI  - Survival of dental implants in native and grafted bone in irradiated head and
      neck cancer patients: a retrospective analysis.
AB  - AIM: To study the long-term survival of dental implants placed in native or
      grafted bone in irradiated bone in subjects who had received radiation for head
      and neck cancer. MATERIALS AND METHODS: A retrospective chart review was
      conducted for all patients who received dental implants following radiation
      treatment for head and neck cancer between May 1, 1987 and July 1, 2008. Only
      patients irradiated with a radiation dose of 50 Gy or greater and those who
      received dental implants in the irradiated field after head and neck radiation
      were included in the study. The associations between implant survival and
      patient/implant characteristics were estimated by fitting univariate marginal Cox
      proportional hazards models. RESULTS: A total of 48 patients who had prior head
      and neck radiation had 271 dental implants placed during May 1987-July 2008.
      There was no statistically significant difference between implant failure in
      native and grafted bone (P=0.76). Survival of implants in grafted bone was 82.3%
      and 98.1% in maxilla and mandible, respectively, after 3 years. Survival of
      implants in native bone in maxilla and mandible was 79.8% and 100%, respectively,
      after 3 years. For implants placed in the native bone, there was a higher
      likelihood of failure in the maxilla compared to the mandible and there was also
      a tendency for implants placed in the posterior region to fail compared to those
      placed in the anterior region. CONCLUSION: There was no significant difference in
      survival when implants were placed in native or grafted bone in irradiated head
      and neck cancer patients. For implants placed in native bone, survival was
      significantly influenced by the location of the implant (maxilla or mandible,
      anterior or posterior).

PMID- 22406707
TI  - Reliability of acridine orange fluorescence microscopy in oral cytodiagnosis.
AB  - CONTEXT AND AIMS: The oral cavity is the most predominant location in the head
      and neck region for primary malignant epithelial tumors. Oral cancer is estimated
      to be the sixth most common malignancy. Early recognition is imperative for
      successful treatment and good prognosis. Exfoliative cytology is a simple and
      reasonably effective technique for rapid initial evaluation of a suspicious oral
      lesion. The present study was conducted to determine the reliability of acridine
      orange fluorescence microscopy for cytodiagnosis as a more rapid and easier
      method for the final evaluation of the cytological specimen. MATERIALS AND
      METHODS: Smears were collected from 20 individuals with oral lesions suspicious
      of malignancy, oral lesions not suggestive of malignancy and normal buccal
      mucosa. One smear was stained with Papanicolaou stain and another one with
      acridine orange stain. The differences in the study group and control group were
      compared by means of the chi2 (Chi-square) test. The results were considered
      statistically significant whenever P was <0.05. RESULTS: The acridine orange
      fluorescence stain reliably demonstrated malignant cells based on the
      differential fluorescence - a cytochemical criterion. The efficacy of the stain
      was higher than the conventional Papanicolaou stain in screening of oral lesions
      suspicious of malignancy. However, the acridine orange fluorescence stain did not
      differentiate effectively between malignant cells and rapidly proliferating
      cells, as the technique is based on the nucleic acid content. CONCLUSION: The
      fluorescent acridine orange method can be used reliably for the screening of
      carcinomas and it is especially helpful in the follow-up detection of recurrent
      carcinoma in previously treated cases.

PMID- 22406708
TI  - Evaluation of treatment for functional posterior crossbite of the deciduous
      dentition using Planas' direct tracks.
AB  - BACKGROUND: Functional posterior crossbites are a common finding in children with
      deciduous teeth and must be treated as soon as they are diagnosed in order to
      avoid unwanted changes in normal growth and development patterns. OBJECTIVE: This
      study objective was to evaluate the changes caused by Planas' direct tracks
      treatment on the arch dimensions of patients with functional posterior crossbite
      in first dentition. MATERIALS AND METHODS: The sample consisted of 20 children, 4
      to 6 years old, divided into two groups, paired up according to age and gender.
      Group test was composed of 10 patients with functional posterior crossbite
      treated with PDT. Group control consisted of 10 children with normal occlusion.
      The evaluation criteria were intercanine and intermolar distances and Carrea's
      analysis (arch perimeter). All data were collected by a pre-calibrated examiner
      on study casts obtained at baseline and after 4 months of treatment. The
      statistical analysis of the data was achieved using GraphPad InStat software,
      version 3.05 for Windows, with the level of significance set at 0.05. For the
      comparison between intercanine and intermolar distances, the Tukey-Kramer
      Multiple Comparisons test was used. When Carrea's analysis was considered, the
      Mann-Whitney test was used. RESULTS: At the beginning of the study, all the
      evaluated criteria showed lower mean values in patients with posterior
      crossbites, and significant differences between test and control groups were
      noticed (P<0.05). After the end of follow-up period, these differences could not
      be verified (P>0.05). CONCLUSIONS: Within the limits of the present study, it is
      possible to conclude that the treatment with Planas' direct tracks was able to
      give back the normal dimensions of deciduous arch in patients with unilateral
      functional posterior crossbites, thus making it possible a better growth pattern.

PMID- 22406709
TI  - Root canal debris removal using different irrigating needles: an SEM study.
AB  - AIM: This study was carried out to compare the efficacy of three irrigating
      needle designs in removal of debris from different parts of the root canal.
      MATERIALS AND METHODS: Thirty human maxillary canines were prepared using HERO
      Shaper rotary system and irrigated with 1 ml of 5.25% sodium hypochlorite (NaOCl)
      after each instrument change. Three 25-gauge irrigation needle designs - brush
      covered Navi Tip FX (Group I), side-vented needle RC Twents (Group II) and single
      beveled (Group III) irrigating needles - were tested for their efficiency in
      debris removal in three different parts of the root canal (n=10 canals per
      group). Following instrumentation, the roots were vertically sectioned and
      divided into coronal, middle and apical thirds for observation under scanning
      electron microscope (*200 magnification). Debris on the canal wall was evaluated
      by using a four-scale scoring system described by Paque and his co-workers.
      RESULTS: The canals irrigated with brush-covered needle Navi Tip FX (Group I)
      showed lower average debris score, indicating greater removal of debris in
      coronal third as compared to middle and apical thirds, whereas the canals
      irrigated with side-vented needle (Group II) and single-beveled needle (Group
      III) exhibited lower average score in the middle third than coronal and apical
      thirds. All the three needle designs exhibited higher debris score in apical
      third of the root canal. Tukey multiple comparisons test was applied at a
      significance level of P>0.05. A statistically significant difference (P<0.05) was
      observed in the debris removal in the coronal and middle thirds of root canals
      irrigated with brush-covered Navi Tip FX (Group I) and side-vented (Group II)
      needles, respectively, when compared with other needle design groups. CONCLUSION:
      Within the limitations of this study, it can be concluded that all the needle
      designs tested were effective in certain regions of the root canal with apical
      third uncleaned. Side-vented needle by creating turbulence removed debris
      effectively in coronal and middle thirds.

PMID- 22406710
TI  - A comparison of lip prints between Aryans-Dravidians and Mongols.
AB  - CONTEXT: Lip prints are very useful in forensic investigation and personal
      identification. Like finger prints, even lip prints can be instrumental in
      identifying a person positively. AIMS: Indians are closer to Mongoloids than to
      Caucasoids or Negroids as indicated by the phylogenetic tree. Most of the studies
      on lip prints are done in their own population. We have compared lip prints of
      Manipuris with other Indians (Aryans and Dravidians) who are both close to
      Mongoloid race and are genetically similar. MATERIALS AND METHODS: A total of 100
      students 50 males and 50 females were selected of whom 30 males and 30 females
      were of Aryan and Dravidian features and 20 males and 20 females showed the
      Mongol features. Study materials used were Red colored lipstick, Lip brush,
      Cellophane tape, White chart paper and Magnifying lens. The lip prints were
      analyzed by dividing them into eight compartments. RESULTS: Analysis of lip
      prints showed that the most common and the least common pattern in both males and
      females (Aryans-Dravidians and Mongols) were the same, but the compartment wise
      distribution of the lip patterns was different. CONCLUSION: In the present study,
      it is established that there is no similarity of lip prints from one individual
      to another individual and between males and females. Regarding the comparison
      with Mongols, more studies with a larger sample size is necessary.

PMID- 22406711
TI  - Dental consultation in patients planned for/undergoing/post radiation therapy for
      head and neck cancers: a questionnaire-based survey.
AB  - BACKGROUND: Mouth and pharyngeal cancers account for approximately 6% of cancers
      worldwide. Radiotherapy is one of the means of treatment of head and neck cancer.
      Consultation with a dental team experienced in caring for patients undergoing
      treatment for head and neck cancer will improve the quality of life of such
      patients. AIMS AND OBJECTIVES: To evaluate the attitude of oncologists toward
      dental consultation to patients planning for/prior to/undergoing/post radiation
      therapy for head and neck cancers and to evaluate the number of radiation
      oncologists who encounter oral complaints and consider worth referring to a
      dentist. MATERIALS AND METHODS: A questionnaire-based study was carried out
      following mailing of covering letter and self-administered questionnaire
      comprising 11 items, to 25 radiation oncology centers selected in India based on
      convenient sampling. RESULTS: Out of the 25 centers, we received response from 20
      centers with 60 completely filled questionnaires. Five centers did not respond
      for further correspondences. CONCLUSION: The study indicated a need for awareness
      and education among radiation oncologists regarding dental consultation in
      patients planned/undergoing /post radiation therapy for head and neck cancer.

PMID- 22406712
TI  - Elongated styloid process: is it a pathologic condition?
AB  - OBJECTIVES: The aims of this study were to evaluate the length, morphology, and
      calcification patterns of the elongated stylohyoid process (ESP) on panoramic
      radiographs and to investigate the symptoms related to it. We then addressed the
      question: Is ESP a pathologic condition or a physiologic phenomenon? MATERIALS
      AND METHODS: In this study, 207 stylohyoid complexes were evaluated based on
      length, radiographic appearance, and calcification pattern on panoramic
      radiographs. Similar to previous studies, we considered 30 mm as a threshold for
      elongation of the process. Complexes were classified into two groups based on
      length: ESP (greater than or equal to 30 mm) and normal (less than 30 mm).
      Clinical symptoms were evaluated by using a questionnaire and clinical
      examination. Data were analyzed by the Kolmogorov-Smilonov test, Mann-Whitney U
      test, and Spearman correlation. RESULTS: The average length of the stylohyoid
      complex was 31.7 mm. The median was 30.0 mm and corresponded to the threshold for
      the ESP. The Spearman correlation between the length of the complex and age was
      0.323 (P=0.0001). "Continuous" and "calcified outline" were the most frequent
      morphology and calcification pattern, respectively, for both groups. Clinical
      symptoms related to ESP were not detected. CONCLUSION: Classification of the
      stylohyoid complexes based on apparent length on panoramic radiographs in
      elongated and normal types appears to be incorrect. Considering that the
      radiographic appearance of the ESP and normal groups was similar and pathologic
      symptoms were not detected and that there was a relationship between age and
      length of the complex, elongation of this complex can be considered as a
      physiologic phenomenon.

PMID- 22406713
TI  - Changes in peripheral innervation and nociception in reticular type and erosive
      type of oral lichen planus.
AB  - BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory lesion in oral
      mucosa. Reticular (OLP-R) and erosive (OLP-E) types of OLP are the common forms
      that have been found in dental clinics. The aim of this investigation is to
      determine the correlation between neurogenic inflammation and nociception
      associated with OLP-R and OLP-E. MATERIALS AND METHODS: The oral mucosal lesions
      from six patients with OLP-E, four with OLP-R and three with noninflamed oral
      mucosa, which represent normal mucosa, were identified by morphometric analysis
      of nerve fibers containing immunoreactive protein gene product (PGP) 9.5. The
      level of inflammation was measured with hematoxylin and eosin staining and the
      level of nociception was analyzed with visual analog scale measurement. RESULTS:
      We found that 1) an increase in peripheral innervation was related to the size of
      the area of inflammatory cell infiltration from both OLP-R and OLP-E; 2) the
      pattern of PGP 9.5-immunoreactivity among OLP-R and OLP-E was not significantly
      different (P=0.23); and 3) the correlation between nociception and an increase in
      PGP 9.5-immunoreactivity was not found in OLP-E and in OLP-R. CONCLUSIONS: Our
      findings suggest that an increase in peripheral innervation may lead to increased
      inflammation, which is part of the immunopathogenesis of OLP. Differences in
      nociception between OLP-R and OLP-E arise from the pathogenesis of each lesion,
      not from the differences in peripheral innervation.

PMID- 22406714
TI  - "Rx--the mistakes we make!!": a short study.
AB  - CONTEXT: There is concern regarding the irrational production, prescription and
      use of drugs in India. AIM: This study aimed to describe the quality of
      prescriptions by dental practitioners of one particular college in a short period
      of time. MATERIALS AND METHODS: A survey of all prescriptions dispensed from the
      various departments of K.L.E.S.'s Institute of Dental Sciences, Belgaum,
      Karnataka, was conducted by collecting them from the patients exiting the college
      premises. The prescriptions were photocopied and handed back to the patients. The
      samples were collected over a period of 7 days. The samples were then analyzed
      for their content based on an ideal prescription format and the results were
      tabulated. RESULTS: The findings of the study suggest that most of the
      prescriptions given are woefully inadequate in content. CONCLUSIONS: It can be
      concluded that a clear policy about the standard of prescriptions and periodic
      internal monitoring is the answer for quality prescriptions. Computerization of
      the prescription format is also a thought-provoking alternative.

PMID- 22406715
TI  - Orofacial manifestation of hematological disorders: hemato-oncologic and immuno
      deficiency disorders.
AB  - The aim of this paper is to review the literature and identify orofacial
      manifestations of hematological diseases with special reference to hemato
      oncologic, immuno-deficiency disorders, and human immunodeficiency virus
      infection. A computerized literature search using MEDLINE was conducted for
      published articles on orofacial manifestations of hematological diseases with
      emphasis on hemato-oncologic and human immunodeficiency virus (HIV) infection.
      Mesh phrases used in the search were: Oral diseases AND hematological disorders;
      orofacial diseases AND leukemias; orofacial lesions AND lymphomas; orofacial
      diseases AND multiple myeloma, orofacial manifestations AND HIV. The Boolean
      operator "AND" was used to combine and narrow the searches. The full texts of
      these articles were thoroughly examined. References in these articles also were
      manually searched non-Medline articles. Only relevant articles were selected for
      the review. Orofacial manifestation of malignant hematological diseases may
      present as primary clinical features due to infiltration of orofacial tissues, or
      as secondary due to the subsequent infiltration of normal bone marrow elements,
      or tertiary due to the side effects of the treatment. HIV-associated orofacial
      lesion may be a clinical indicator of HIV infection in otherwise healthy,
      undiagnosed individuals; an early clinical feature of HIV infection; clinical
      markers for the classification and staging of HIV disease or may be a predictor
      of HIV disease progression. Orofacial manifestations of malignant hematological
      diseases and HIV infection are not uncommon findings in clinical practice. These
      manifestations may be clinical indicators of hematologic disorders in otherwise
      healthy, undiagnosed individuals.

PMID- 22406716
TI  - Periodontal vaccine.
AB  - Vaccine is the name applied generally to a substance of the nature of dead or
      attenuated living infectious material introduced into the body with the object of
      increasing its power to resist or get rid of a disease. Vaccines are generally
      prophylactic, i.e. they ameliorate the effects of future infection. One such
      vaccine considered here is the "Periodontal vaccine". Till date, no preventive
      modality exists for periodontal disease and treatment rendered is palliative.
      Thus, availability of periodontal vaccine would not only prevent and modulate
      periodontal disease, but also enhance the quality of life of people for whom
      periodontal treatment cannot be easily obtained. The aim of the research should
      be development of a multispecies vaccine targeting the four prime periodontal
      pathogens, viz. Porphyromonas gingivalis, T. forsythus, T. denticola and A.
      comitans. Success is still elusive in case of periodontal vaccine due to the
      complex etiopathogenesis of the disease.

PMID- 22406717
TI  - Microscope-aided endodontic treatment of maxillary first premolars with three
      roots: a case series.
AB  - Maxillary premolars have a highly variable root canal morphology. However, the
      presence of three roots is a rare occurrence. This clinical article describes the
      unusual anatomy detected in maxillary premolars during routine endodontic
      treatment using microscope. The diagnosis and clinical management of maxillary
      first premolars with three roots and canals using radiographic interpretation,
      access cavity modification and visual enhancement with operative microscopes is
      discussed in the article.

PMID- 22406718
TI  - Marsupialization of unicystic ameloblastoma: a conservative approach for
      aggressive odontogenic tumors.
AB  - Unicystic ameloblastoma (UA) is known as a distinct entity which has a less
      aggressive behavior when compared with conventional ameloblastoma. In this
      report, we have presented two cases of UAs, (of which one case showed a more
      aggressive behavior with mural invasion into the adjacent tissues and granular
      cell differentiation), both of which were successfully managed with enucleation
      following marsupialization. We aim to highlight how this method can be used for
      the successful management of such cases, rather than following more aggressive
      approaches. In both the cases, marsupialization was done for the UA lesions
      initially and follow-ups were maintained. When the tumor size had regressed on
      radiographic follow up, an enucleation procedure with ostectomy of the margins
      was carried out. Special importance was also given to the endodontic treatment of
      the teeth involved in the area of the lesion. The patients were free of the
      condition and did not show any signs of recurrence on radiographic follow-ups
      even after 30 months of the final procedure. Granular variant of UA is quite rare
      and had been considered to be more aggressive. Marsupialization of UA is an
      alternative treatment option of resection even for more aggressive variants, as
      long as the histological behavior of the lesion was carefully evaluated and
      strict radiographic follow-up is maintained.

PMID- 22406719
TI  - Rare foreign bodies in oro-facial regions.
AB  - Accidental entry of foreign bodies into the oro-facial region could be due to
      trauma, therapeutic interventions or iatrogenic. Various foreign bodies and
      locations have been reported, for example, wood in the orbit, impression material
      in the maxillary sinus, tooth fragments in the orbit. All these cases presented
      with inflammatory reaction and formation of infected granuloma, pus discharging
      sinus and serious complications like intra-cranial abscesses. Foreign bodies
      sometimes migrate within the tissues and become symptomatic after a certain
      period of time. In these cases, it is very difficult to correlate the direct
      relation between the suspected foreign bodies with the present clinical symptoms.
      The removal of foreign bodies is often a surgical challenge due to a combination
      of difficulty in access and close anatomical relationship to vital structures. To
      prevent complications, foreign bodies should be diagnosed and removed on time.

PMID- 22406720
TI  - An innovative technique for customizing the stock acrylic resin ocular
      prosthesis.
AB  - The loss of an eye is a traumatic and common event. The psychological effects of
      losing an eye are frequently more difficult to deal with than its functional
      loss. This article describes the management of a child patient with anopthalmic
      socket, by an innovative technique of customizing the stock acrylic resin ocular
      prosthesis to get improved esthetics, accurate location of iris-pupil complex and
      exact fit in the defect.

PMID- 22406721
TI  - Prosthetic rehabilitation of large nasal septal defect with an intranasal stent:
      a clinical report.
AB  - Nasal septal perforation is a common complication of many nasal diseases such as
      congenital, infectious, trauma, and iatrogenic, and rarely may occur as a
      complication of systemic diseases, etc. The symptoms of uncorrected nasal septal
      perforations include crusting, epistaxis, difficulty in breathing, nasal twang in
      speech, postnasal discharge, foul-smelling, rhinorrhea, and hyposmia. Large nasal
      defects cannot be closed by hard acrylic resin nasal septal obturators because of
      the problems in access and path of insertion. However, obturation can be achieved
      by fabrication of a nasal stent that engages one of the nasal cavities. This
      clinical report describes prosthetic management of a patient with large nasal
      septal defect following septal surgery complication with an intranasal heat
      processed acrylic resin stent. The stent is rendered patent for comfortable
      breathing, improves speech, is esthetically acceptable, dense and hygienic. These
      nasal stents indirectly separate the two nasal cavities with effective obturation
      of large nasal septal defects.

PMID- 22406722
TI  - Mandibular fracture in an 18-month-old child.
AB  - Facial trauma in a child can be a greatly distressing experience for the parents
      as well as the child, causing uncontrollable crying in the child and panic and
      fear in the parents. Facial injuries in children are less common than in adults.
      This case report describes the management of symphysial fracture of the mandible
      in an 18-month-old girl. The fracture was reduced under general anesthesia and
      then stabilized with an acrylic cap splint, utilizing circummandibular wiring.

PMID- 22406723
TI  - Root coverage using epithelial embossed connective tissue graft.
AB  - In periodontal practice, root coverage after marginal soft tissue recession
      requires daily clinical decisions. Numerous longitudinal human studies have been
      presented to support the efficacy and predictability of different mucogingival
      surgical techniques for root coverage. Over the years, root coverage procedure
      using the subepithelial connective tissue graft with variations has emerged as
      the favorite surgical technique. In the case presented in this report,
      subepithelial connective tissue graft with embossed epithelium was used to cover
      Miller's class II gingival recession in the upper right canine. The design is
      such that embossed epithelium exactly fits the recession site and the connective
      tissue portion is tucked below the gingival margin of the recipient site. In this
      technique, coronal advancement of flap is not needed. Wider zone of attached
      gingiva at the recipient site was achieved by this technique.

PMID- 22406724
TI  - Trismus as a first presenting complaint in a case of myasthenia gravis.
AB  - The initial presentation of myasthenia gravis as trismus is very rare and no
      previous reports have been found in the literature. A 35-year-old male presented
      to the outpatient unit of our department with inability to clench well and to
      open his mouth. Physical examination revealed that he had clinical findings
      consistent with the signs and symptoms of myasthenia gravis. He was immediately
      referred to a neurologist, who confirmed that he was in an advanced stage of
      myasthenia gravis with severe deficit to his respiratory muscles and he was
      promptly treated. He is presently on a maintenance drug therapy. To our
      knowledge, this is the first reported case of myasthenia gravis whose initial
      presentation was trismus. This case presents a rare but important diagnosis that
      should be added to the differential diagnosis of trismus.

PMID- 22406725
TI  - In vitro wear of Ionofil Molar AC quick glass-ionomer cement.
AB  - AIM: The aim of this study was to evaluate the three-body wear-resistance of one
      type of restorative glass-ionomer cement (GIC). MATERIALS AND METHODS: Specimen
      including conventional GIC (Ionofil Molar AC Quick: IMACQ), hybrid ionomer (Fuji
      II LC), and composite resin (Heliomolar) were tested in a wearing machine. In
      this machine, a 6 kg load was applied via pressable chromium-cobalt bar at 5,000,
      10,000, 20,000, 40,000, 80,000, 120,000 cycles. Specimen weight was measured by
      an electronical weight balance before and after each cycle. Data were analyzed
      using one-way analysis of variance (ANOVA) followed by a t-test, and a paired t
      test at P<=0.05. RESULTS: The highest weight loss has been found in Fuji II LC,
      then in GIC IMACQ and the least wear rate has been reported in heliomolar
      composite in all cycles except 120,000 cycles. In 120,000 cycles, the highest
      weight loss was seen in GIC IMACQ, then Fuji II LC, and finally heliomolar
      composite. There was a statistically significant difference in weight loss
      between GIC IMACQ and heliomolar composite (P=0/001). CONCLUSION: The wear rate
      of GIC IMACQ was between those of heliomolar composite and Fuji II LC glass
      ionomer in all cycles except 120,000 cycles. The most important advantage of this
      new-generation glass ionomer is its good manipulability and also high wear
      resistance compared to the hybrid ionomer. Therefore, it is suggested that it can
      be used as restorative material in class I restorations in primary teeth.

PMID- 22406726
TI  - A comparative evaluation of the shear bond strength of five different orthodontic
      bonding agents polymerized using halogen and light-emitting diode curing lights:
      an in vitro investigation.
AB  - PURPOSE: With the introduction of photosensitive (light-activated) restorative
      materials in orthodontics, various methods have been suggested to enhance the
      polymerization of the materials used, including use of more powerful light curing
      devices. Bond strength is an important property and determines the amount of
      force delivered and the treatment duration. Many light-cured bonding materials
      have become popular but it is the need of the hour to determine the bonding agent
      that is the most efficient and has the desired bond strength. AIM: To evaluate
      and compare the shear bond strengths of five different orthodontic light cure
      bonding materials cured with traditional halogen light and low-intensity light
      emitting diode (LED) light curing unit. MATERIALS AND METHODS: 100 human
      maxillary premolar teeth, extracted for orthodontic purpose, were used to prepare
      the samples. 100 maxillary stainless steel bicuspid brackets of 0.018 slot of
      Roth prescription, manufactured by D-tech Company, were bonded to the prepared
      tooth surfaces of the mounted samples using five different orthodontic bracket
      bonding light-cured materials, namely, Enlight, Fuji Ortho LC (resin-modified
      glass ionomer cement), Orthobond LC, Relybond, and Transbond XT. The bond
      strength was tested on an Instron Universal testing machine (model no. 5582).
      RESULTS: In Group 1 (halogen group), Enlight showed the highest shear bond
      strength (16.4 MPa) and Fuji Ortho LC showed the least bond strength (6.59 MPa)
      (P value 0.000). In Group 2 (LED group), Transbond showed the highest mean shear
      bond strength (14.6 MPa) and Orthobond LC showed the least mean shear bond
      strength (6.27 MPa) (P value 0.000). There was no statistically significant
      difference in the shear bond strength values of all samples cured using either
      halogen (mean 11.49 MPa) or LED (mean 11.20 MPa), as the P value was 0.713.
      CONCLUSION: Polymerization with both halogen and LED resulted in shear bond
      strength values which were above the clinically acceptable range given by
      Reynolds. The LED light curing units produced comparable shear bond strength to
      that of halogen curing units.

PMID- 22406727
TI  - Comparison of oral manifestations with CD4 count in HIV-infected patients.
AB  - AIM AND OBJECTIVE: This study was carried out with the primary aim of correlating
      oral changes and general changes of HIV-infected patients with their CD4 count.
      MATERIALS AND METHODS: 124 patients were selected, and after taking their
      informed consent, they were subjected to detailed history taking and thorough
      clinical examination. Specific oral lesions and general physical changes were
      recorded. Every patient was subjected to laboratory investigation for CD4 count.
      All these findings were tabulated. The clinical observation and laboratory
      findings were subjected to critical analysis and correlated. Statistical test,
      i.e. Student's " t" test, was applied and objective conclusions were drawn.
      RESULT: Out of 124 patients, 40 had oral candidiasis, 6 had oral hairy
      leukoplakia, 12 had periodontal disease, 20 had xerostomia, 30 had melanin
      pigmentation, while 4 had HSV2, and atypical ulceration. Out of 40 patients with
      oral candidiasis, 28 patients had CD4 count <200 (group A), 10 patients were in
      group, B (CD4 count 200-500 cell/mm 3 ) and 2 patients in group C(CD4 >500
      cell/mm 3 ). Oral hairy leukoplakia occurred in equal proportions in group A and
      B. These periodontal diseases were more commonly in group B; xerostomia and
      melanin pigmentation was equally seen in group A and B. CONCLUSION: Oral
      candidiasis, oral hairy leukoplakia, linear gingival erythema, necrotizing
      ulcerative gingivitis, and necrotizing ulcerative periodontitis are specific oral
      indicators which will definitely suggest to the dental surgeon that the disease
      is running a rapid downhill course and due to this the oral physician is in a
      position to raise a suspicion and alert the general physician regarding the
      declining immune status of patient.

PMID- 22406728
TI  - Evaluation and comparison of castability between an indigenous and imported Ni-Cr
      alloy.
AB  - CONTEXT: Since 1907 casting restorations have been in use in dentistry. Numerous
      companies have been manufacturing and marketing base metal alloys. Gold was a
      major component of casting alloys. But alloys with less than 65% gold tarnished
      easily and the increase in cost of gold post-1970s lead to the revival of base
      metal alloys such as nickel-chromium and cobalt-chromium alloys which were in use
      since 1930s. AIM: This study was conducted to evaluate and compare the
      castability between an indigenous alloy and an imported alloy, as imported base
      metal alloys are considered to be expensive for fabrication of crowns and
      bridges. MATERIALS AND METHODS: This study was conducted to evaluate and compare
      the castability (for the accurate fabrication of crowns and bridges) between an
      indigenous base metal alloy-Non-ferrous Materials Technology Development Centre
      (NFTDC), Hyderabad (Alloy A) -and an imported base metal alloys (Alloy B).
      Castability measurement was obtained by counting the number of completely formed
      line segments surrounding the 81 squares in the pattern and later calculating the
      percentage values. The percentage obtained was taken as the castability value for
      a particular base metal alloy. The percentage of castability was determined by
      counting only the number of completely cast segments in a perfect casting (81 * 2
      = 162), and then multiplying the resulting fraction by 100 to give the percentage
      completeness. STATISTICAL ANALYSIS USED: The Student t-test was used. RESULTS:
      When the castability of alloys A and B was compared, the calculated value was
      less than the tabular value (1.171 < 2.048) leading to the conclusion that
      castability between alloys A and B is insignificant. Therefore we conclude that
      both the alloys have the same castability. CONCLUSIONS: Using the above-mentioned
      materials and following the method to test castability, we were able to derive
      favorable results. As the results were satisfactory, we can conclude that the
      castability of the indigenous alloy is on par with the imported alloy.

PMID- 22406729
TI  - New generation of color bonding: a comparative in vitro study.
AB  - BACKGROUND: Newer available composite resin adhesives have chromatic agents that
      change their color during setting from pink to colorless. It has an advantage of
      easy flash removal thus reducing the amount of plaque accumulation and helping
      patients to maintain better hygiene. AIM: The aim of the present study was to
      compare shear bond strengths of light-cure orthodontic bonding agents, namely
      glass ionomer (FujiOrthoLC, GC Orthodontics), conventional composite resin
      (Transbond XT, 3M Unitek), and color-changing composite resin (Transbond Plus, 3M
      Unitek) with conventional etch and self-etch primer (Transbond PlusSEP, 3M
      Unitek). MATERIALS AND METHODS: Maxillary premolars (n=300) were bonded on the
      facial surface in five groups. The INSTRON machine was used for shear bond
      strength testing. STATISTICAL ANALYSIS: Comparison of the mean rank among the
      groups was done by Kruskal-Wallis one-way analysis of variance (ANOVA). To
      determine the mean difference among groups, the Mann-Whitney test with Bon
      Ferroni adjustment was applied. OBSERVATIONS: It was observed that light-cure
      conventional composite resin with the conventional etchant group had the highest
      and glass ionomer resin adhesive had the lowest shear bond strength. There was no
      statistically significant difference between conventional composite used with
      conventional etchant and color-changing composite resin used with conventional
      etchant or with self-etch primer. CONCLUSION: Considering the advantages of a
      color-changing composite and self-etch primer especially in patients having high
      DMFT scores or physically and mentally compromised patients unable to maintain
      their hygiene properly, it was concluded in the present study that it would be
      the most suitable material for direct bonding.

PMID- 22406730
TI  - eRME--rapid maxillary expansion in the economic way.
AB  - AIM AND OBJECTIVES: Rapid Maxillary Expansion constitutes a routine clinical
      procedure in orthodontics, involving separation of mid-palatine suture which is
      usually done with help of the Hyrax screw. However, because of its high cost, the
      use has been limited, especially in institutions. So, the purpose of this study
      was to construct an economical device which can expand the maxillary arch in
      growing patients. MATERIALS AND METHODS: Six patients having constricted maxilla
      and posterior skeletal crossbite were randomly selected from the Department of
      Orthodontics. A unique, easy and simple alternative device for expanding the
      maxillary arch called economic Rapid Maxillary Expander (eRME) has been
      fabricated at about one-tenth the cost of the conventional Hyrax. Pre- and post
      treatment effects were statistically tested by using paired t-test at 0.05 level
      of significance. RESULTS AND CONCLUSION: The study results showed an average
      expansion in canine, premolar and molar regions of 4.4 mm, 6.8 mm and 9.4 mm,
      respectively, having significant difference pre-and post-treatment. Thus, it
      shows that maxillary expansion is efficiently possible with the application of
      this newly constructed device named eRME. This appliance also acts as a fixed
      retainer to avoid relapse, hence negating the need for a separate retainer.

PMID- 22406731
TI  - Awareness of association between periodontitis and PLBW among selected population
      of practising gynecologists in Andhra Pradesh.
AB  - CONTEXT: Preterm low-birth-weight (PLBW) infants are at a higher risk for a
      number of acute and chronic disorders. Studies point to an association between
      periodontal infection and increased rates of preterm birth, and pregnant mothers
      with periodontal diseases are at increased risk of subsequent preterm birth or
      low birth weight. However, the awareness level of gynecologists about this
      relationship is unknown. AIMS: The aim of the present survey was to assess the
      awareness about the effects of periodontal disease on pregnancy among practicing
      gynecologists, and also compare such awareness between gynecologists in two
      places-Khammam (a district headquarter) and Hyderabad (a state capital). SETTINGS
      AND DESIGN: Random, cross-sectional study in a population of practicing
      gynecologists from Andhra Pradesh. MATERIALS AND METHODS: A random study
      population was selected from the practicing gynecologists in Khammam and
      Hyderabad. Sixty practicing gynecologists, 30 each in Khammam and Hyderabad, were
      approached and they consented to join the study. Data were collected in
      questionnaire format from the subject population. Collected data were
      statistically analyzed. Chi-square test with Yates correction was used to analyze
      the data. A " P" value of <0.05 was taken as a significant difference. RESULTS:
      73.3% of the gynecologists said that their patients complain of bleeding gums,
      swellings and mobility. 58.3% of the gynecologists were aware that gum diseases
      occur at a higher rate in pregnant females. 38.3% of the gynecologists were aware
      that periodontal diseases can affect the outcome of delivery. No significant
      difference was found between the awareness levels of gynecologists in Khammam and
      in Hyderabad. CONCLUSIONS: There is a need for interdisciplinary approach for the
      prevention of PLBW cases by the integration of periodontal care into obstetric
      management. Effort should be made to increase awareness among the gynecologists.

PMID- 22406732
TI  - Evaluation of DNA damage in oral precancerous and squamous cell carcinoma
      patients by single cell gel electrophoresis.
AB  - CONTEXT: Single cell gel electrophoresis (SCGE) or "comet assay" is a rapid and
      very sensitive fluorescent microscopic method for detecting various forms of DNA
      damage at individual cell level. AIMS: The aim of the present study was to detect
      the extent of DNA damage in oral cancer, oral submucous fibrosis (OSMF) and
      leukoplakia in comparison to normal individual. SETTINGS AND DESIGN: A total of
      44 consecutive patients with oral cancer (n=26), leukoplakia (n=12) and OSMF
      (n=6) and 10 healthy normal volunteers with normal oral epithelia (controls) were
      recruited from Dr. R. Ahmed Dental College and Hospital and were assessed for the
      extent of DNA damage using SCGE following clinical diagnosis. MATERIALS AND
      METHODS: Peripheral blood was collected by venepuncture and comet assay was
      performed using SCGE. Mean tail length was compared between diagnostic groups and
      between different oral habit groups using t-tests and analysis of variance
      (ANOVA). Pearson's product moment correlation was used to examine the linear
      association between the extent of DNA damage and oral habit pack-years. Scheffe's
      pair-wise test was employed to adjust for multiple comparisons. RESULTS: None of
      the controls were associated with any oral habits. Mean (+/-SD) tail lengths (in
      mm) for cancer (24.95 +/- 5.09) and leukoplakia (12.96 +/- 2.68) were
      significantly greater than in controls (8.54 +/- 2.55, P<0.05). After adjustment,
      well-, moderately, and poorly differentiated carcinomas had significantly greater
      tail length than controls. Whereas the extent of DNA damage in cancer cases was
      significantly greater in leukoplakia than in compared to OSMF (11.03 +/- 5.92),
      the DNA damage in latter was not different from controls. DNA damage for people
      with any oral habit (19.78 +/- 7.77) was significantly greater than those with no
      habits (8.54 +/- 2.55; P<0.0001). CONCLUSIONS: DNA damage measured by SCGE is
      greater in leukoplakia and squamous cell carcinoma, but not in OSMF. Deleterious
      oral habits are also associated with greater DNA damage.

PMID- 22406733
TI  - Displacement of endodontic instruments in inferior alveolar canal.
AB  - Endodontic instrument breakage is a common occurrence during root canal treatment
      but the displacement of the separated instrument into the inferior alveolar canal
      is rare and has never been reported. We hereby present an unusual case of
      displacement of a separated instrument in the inferior alveolar canal and its
      retrieval by a simple technique.

PMID- 22406734
TI  - Benign hyperplasia of duct-associated lymphoid tissue: report of a case and
      review of literature.
AB  - Focal lymphoid tissue is ubiquitously present in the oral mucosa and serves as a
      barrier for entrapment of antigens. The mucosa-associated lymphoid tissue is
      generally dispersed and sometimes associated with the ducts of the minor salivary
      glands. Proliferation of the duct-associated lymphoid tissue (DALT) is rarely
      reported, though probably of common occurrence. We report a case of benign
      hyperplasia of DALT in the buccal mucosa of a 58-year-old male. The histogenesis
      and pathological implications of this tissue are discussed and the need for
      recognition of this entity is stressed.

PMID- 22406735
TI  - Smoking and non-alcoholic steatohepatitis (NASH): the GREek Atorvastatin and
      Coronary heart disease Evaluation (GREACE) trial.

PMID- 22406736
TI  - Focus: Long-term treatment with lamivudine in HBeAg negative patients with
      chronic hepatitis B: to switch or not to switch?

PMID- 22406737
TI  - Dosage-sensitive network in polycystic kidney and liver disease: multiple
      mutations cause severe hepatic and neurological complications.

PMID- 22406738
TI  - Riboflavin as a photosensitizer. Effects on human health and food quality.
AB  - Riboflavin, vitamin B2, and flavins (as riboflavin building blocks or degradation
      products) are efficient photosensitizers inducing oxidative damage to light
      exposed tissue and food by substrate-dependent mechanisms, for which protection
      is offered by specific nutrients. Phenolic and N-heterocyclic amino acids and
      their peptides and proteins deactivate triplet-excited state riboflavin in
      diffusion controlled processes, efficiently competing with deactivation by
      oxygen, resulting in direct (so called Type I) protein degradation through
      electron transfer or proton-coupled electron transfer. In light-exposed tissue,
      such often long lived protein radicals may as primary photoproducts initiate
      lipid and vitamin oxidation. In contrast, for lipid systems, oxygen deactivation
      of triplet-excited state riboflavin, resulting in formation of singlet oxygen, is
      under aerobic conditions faster than direct deactivation by lipids, which
      otherwise under anaerobic conditions occurs as hydrogen atom transfer from
      polyunsaturated lipids to triplet riboflavin. Singlet oxygen adds to unsaturated
      lipids and forms lipid hydroperoxides as primary lipid oxidation products or
      oxidizes proteins (Type II mechanism). Carotenoids seem not to deactivate triplet
      riboflavin, while chromanols like vitamin E and plant polyphenols are efficient
      in such deactivation yielding protection of proteins and lipids by these phenols.
      Indirect protection against the triplet reactivity of riboflavin is further
      important for polyphenols as riboflavin singlet excited state quenchers in
      effectively preventing riboflavin intersystem crossing to yield the reactive
      triplet state. Riboflavin photosensitization becomes critical for degradation of
      proteins, unsaturated lipids, and folate, thiamine, ascorbate and other vitamins
      during light exposure of food during storage. For skin, eye and other tissue
      exposed to high intensity light, dietary polyphenols like flavonoids are
      important in direct protection against photosensitized oxidation, while dietary
      carotenoids may yield protection through inner-filter effects, through scavenging
      of radicals resulting from Type I photosensitization, and through quenching of
      singlet oxygen formed in Type II photosensitization. Both carotenoids and
      polyphenols accordingly counteract the degenerative effect induced by riboflavin
      exposed to light, although by different mechanisms.

PMID- 22406739
TI  - Anomalously suppressed localization in the two-channel Anderson model.
AB  - We study numerically the localization properties of a two-channel quasi-one
      dimensional Anderson model with uncorrelated diagonal disorder within the nearest
      neighbor tight-binding approximation. We calculate and analyze the disorder
      averaged transmittance and the Lyapunov exponent. We find that the localization
      of the entire system is enhanced by increasing the interchain hopping strength t.
      From the numerical investigation of the energy dependence of the Lyapunov
      exponent for many different interchain hopping strengths, we find that apart from
      the band center anomaly, which usually occurs in strictly one-dimensional
      disordered systems, additional anomalies appear at special spectral points. They
      are found to be associated with the interchain hopping strength and occur at E =
      +/- t/2 and +/- t. We find that the anomalies at E = +/- t are associated with
      the pi-coupling occurring within one energy band and those at E = +/- t/2 are
      associated with the pi-coupling occurring between two different energy bands.
      Despite having a similar origin, these two anomalies have distinct
      characteristics in their dependence on the strength of disorder. We also show
      that for a suitable range of parameter values, effectively delocalized states are
      observed in finite-size systems.

PMID- 22406740
TI  - Glucose sensing by ChREBP/MondoA-Mlx transcription factors.
AB  - The paralogous transcription factors ChREBP and MondoA, together with their
      common binding partner Mlx, have emerged as key mediators of intracellular
      glucose sensing. By regulating target genes involved in glycolysis and
      lipogenesis, they mediate metabolic adaptation to changing glucose levels. As
      disturbed glucose homeostasis plays a central role in human metabolic diseases
      and as cancer cells often display altered glucose metabolism, better
      understanding of cellular glucose sensing will likely uncover new therapeutic
      opportunities. Here we review the regulation, function and evolutionary
      conservation of the ChREBP/MondoA-Mlx glucose sensing system and discuss possible
      directions for future research.

PMID- 22406741
TI  - Genetic origins of low birth weight.
AB  - PURPOSE OF REVIEW: Smaller size at birth is associated with a higher risk of type
      2 diabetes in later life, but the mechanisms behind this association are poorly
      understood. Genetic variants which influence susceptibility to type 2 diabetes
      via effects on insulin secretion or action are good candidates for association
      with birth weight because foetal insulin is a key foetal growth factor. This
      review will focus on recent progress in identifying associations between common
      genetic variants and birth weight. RECENT FINDINGS: Foetal genetic variants at
      two loci (near CCNL1 and in ADCY5) were robustly associated with birth weight via
      the foetal genotype in the first genome-wide association study of birth weight.
      The birth weight-lowering allele at ADCY5 also predisposes to type 2 diabetes. In
      addition, evidence from studies of other type 2 diabetes loci is accumulating for
      association between the foetal risk alleles at CDKAL1 and HHEX-IDE and lower
      birth weight, and the maternal risk alleles at GCK and TCF7L2 and higher birth
      weight. SUMMARY: The associations with birth weight at ADCY5, CDKAL1 and HHEX-IDE
      support the foetal insulin hypothesis, which proposed that type 2 diabetes and
      lower birth weight could be two phenotypes of the same genotype. The associations
      at GCK and TCF7L2 illustrate that maternal genes are also important determinants
      of birth weight.

PMID- 22406742
TI  - Three decades of the WHO code and marketing of infant formulas.
AB  - PURPOSE OF REVIEW: The International Code of Marketing of Breast Milk Substitutes
      states that governments, non-governmental organizations, experts, consumers and
      industry need to cooperate in activities aimed at improving infant nutrition.
      However, the evidence from the last three decades is that of a series of
      disputes, legal proceedings and boycotts. The purpose of this review is to assess
      the overall progress in the implementation of the Code and to examine the
      problematic areas of monitoring, compliance and governance. RECENT FINDINGS:
      There are continuing issues of implementation, monitoring and compliance which
      predominantly reflect weak governance. Many Member States have yet to fully
      implement the Code recommendations and most States do not have adequate
      monitoring and reporting mechanisms. Application of the Code in developed
      countries may be undermined by a lack of consensus on the WHO recommendation of 6
      months exclusive breastfeeding. There is evidence of continuing conflict and
      acrimony, especially between non-government organizations and industry. SUMMARY:
      Measures need to be taken to encourage the Member States to implement the Code
      and to establish the governance systems that will not only ensure effective
      implementation and monitoring of the Code, but also deliver the Code within a
      spirit of participation, collaboration and trust.

PMID- 22406743
TI  - Vitamin A supply to mothers and children:  challenges and opportunities.
AB  - PURPOSE OF REVIEW: Although we are close to the centennial of the discovery of
      vitamin A, our understanding of the functions of this major micronutrient is
      still evolving. Given its major role in fetal development, growth, vision,
      immunity and survival, a subtle balance is required between adequate intake to
      avoid deficiency and excessive intake to avoid toxicity, both in low income and
      industrialized countries. RECENT FINDINGS: This review highlights the potential
      impact of vitamin A supplementation (VAS) in mothers and children suffering from
      vitamin A deficiency (VAD) on mortality and morbidities, and warns against the
      increasingly frequent use of bariatric surgery especially to treat severely obese
      childbearing women, which is known to alter vitamin A status. SUMMARY: Despite
      massive vitamin A supplementation public health policies in developing countries,
      the burden of VAD is still common and efforts should be maintained to better
      target populations at risk, and to develop alternative strategies for
      supplementation based on sustainable and integrated approaches. In industrialized
      countries, VAD due to insufficient intake is scarce, but it may surprisingly
      occur due to the decreased absorption of lipids following antiobesity treatments.
      Specific approaches should be developed to better monitor and supplement obese
      childbearing women who have undergone bariatric surgery.

PMID- 22406744
TI  - Gestational weight gain:  influences on the long-term health of the child.
AB  - PURPOSE OF REVIEW: To address the recent evidence which suggests that
      inappropriate gestational weight gain (GWG) may have consequences that extend to
      the longer term health of the child. RECENT FINDINGS: Inadequate GWG is
      associated with low birthweight, and excessive GWG to delivery of large for
      gestational age infants . Recent studies report relationships between excessive
      GWG and neonatal adiposity, and with childhood and adult obesity. These appear to
      be independent of confounders such as socioeconomic status and a shared family
      environment, or hereditary traits for obesity, supporting the 'developmental
      origins of disease' hypothesis. SUMMARY: Because of periods of developmental
      plasticity, the early life metabolic environment may contribute to the risk of
      metabolic and cardiovascular disease in later life. The mechanisms which explain
      the relationships between maternal GWG and later life obesity remain unknown.
      Large, well conducted, intervention randomized controlled trials in pregnant
      women are required to address relationships between GWG and offspring risk of
      disease, including characterization of potential mediators. These should lead to
      more targeted and effective intervention strategies.

PMID- 22406745
TI  - Functional engraftment of colon epithelium expanded in vitro from a single adult
      Lgr5+ stem cell.
AB  - Adult stem-cell therapy holds promise for the treatment of gastrointestinal
      diseases. Here we describe methods for long-term expansion of colonic stem cells
      positive for leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5(+)
      cells) in culture. To test the transplantability of these cells, we reintroduced
      cultured GFP(+) colon organoids into superficially damaged mouse colon. The
      transplanted donor cells readily integrated into the mouse colon, covering the
      area that lacked epithelium as a result of the introduced damage in recipient
      mice. At 4 weeks after transplantation, the donor-derived cells constituted a
      single-layered epithelium, which formed self-renewing crypts that were
      functionally and histologically normal. Moreover, we observed long-term (>6
      months) engraftment with transplantation of organoids derived from a single
      Lgr5(+) colon stem cell after extensive in vitro expansion. These data show the
      feasibility of colon stem-cell therapy based on the in vitro expansion of a
      single adult colonic stem cell.

PMID- 22406746
TI  - A systems approach identifies HIPK2 as a key regulator of kidney fibrosis.
AB  - Kidney fibrosis is a common process that leads to the progression of various
      types of kidney disease. We used an integrated computational and experimental
      systems biology approach to identify protein kinases that regulate gene
      expression changes in the kidneys of human immunodeficiency virus (HIV)
      transgenic mice (Tg26 mice), which have both tubulointerstitial fibrosis and
      glomerulosclerosis. We identified homeo-domain interacting protein kinase 2
      (HIPK2) as a key regulator of kidney fibrosis. HIPK2 was upregulated in the
      kidneys of Tg26 mice and in those of patients with various kidney diseases. HIV
      infection increased the protein concentrations of HIPK2 by promoting oxidative
      stress, which inhibited the seven in absentia homolog 1 (SIAH1)-mediated
      proteasomal degradation of HIPK2. HIPK2 induced apoptosis and the expression of
      epithelial-to-mesenchymal transition markers in kidney epithelial cells by
      activating the p53, transforming growth factor beta (TGF-beta)-SMAD family member
      3 (Smad3) and Wnt-Notch pathways. Knockout of HIPK2 improved renal function and
      attenuated proteinuria and kidney fibrosis in Tg26 mice, as well as in other
      murine models of kidney fibrosis. We therefore conclude that HIPK2 is a potential
      target for anti-fibrosis therapy.

PMID- 22406747
TI  - Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic
      acid differentiation pathway in acute myeloid leukemia.
AB  - Acute promyelocytic leukemia (APL), a cytogenetically distinct subtype of acute
      myeloid leukemia (AML), characterized by the t(15;17)-associated PML-RARA fusion,
      has been successfully treated with therapy utilizing all-trans-retinoic acid
      (ATRA) to differentiate leukemic blasts. However, among patients with non-APL
      AML, ATRA-based treatment has not been effective. Here we show that, through
      epigenetic reprogramming, inhibitors of lysine-specific demethylase 1 (LSD1, also
      called KDM1A), including tranylcypromine (TCP), unlocked the ATRA-driven
      therapeutic response in non-APL AML. LSD1 inhibition did not lead to a large
      scale increase in histone 3 Lys4 dimethylation (H3K4(me2)) across the genome, but
      it did increase H3K4(me2) and expression of myeloid-differentiation-associated
      genes. Notably, treatment with ATRA plus TCP markedly diminished the engraftment
      of primary human AML cells in vivo in nonobese diabetic (NOD)-severe combined
      immunodeficient (SCID) mice, suggesting that ATRA in combination with TCP may
      target leukemia-initiating cells. Furthermore, initiation of ATRA plus TCP
      treatment 15 d after engraftment of human AML cells in NOD-SCID gamma (with
      interleukin-2 (IL-2) receptor gamma chain deficiency) mice also revealed the ATRA
      plus TCP drug combination to have a potent anti-leukemic effect that was superior
      to treatment with either drug alone. These data identify LSD1 as a therapeutic
      target and strongly suggest that it may contribute to AML pathogenesis by
      inhibiting the normal pro-differentiative function of ATRA, paving the way for
      new combinatorial therapies for AML.

PMID- 22406748
TI  - Down-regulation of OPA1 alters mouse mitochondrial morphology, PTP function, and
      cardiac adaptation to pressure overload.
AB  - AIMS: The optic atrophy 1 (OPA1) protein is an essential protein involved in the
      fusion of the mitochondrial inner membrane. Despite its high level of expression,
      the role of OPA1 in the heart is largely unknown. We investigated the role of
      this protein in Opa1(+/-) mice, having a 50% reduction in OPA1 protein expression
      in cardiac tissue. METHODS AND RESULTS: In mutant mice, cardiac function assessed
      by echocardiography was not significantly different from that of the Opa1(+/+).
      Electron and fluorescence microscopy revealed altered morphology of the Opa1(+/-)
      mice mitochondrial network; unexpectedly, mitochondria were larger with the
      presence of clusters of fused mitochondria and altered cristae. In permeabilized
      mutant ventricular fibres, mitochondrial functional properties were maintained,
      but direct energy channelling between mitochondria and myofilaments was weakened.
      Importantly, the mitochondrial permeability transition pore (PTP) opening in
      isolated permeabilized cardiomyocytes and in isolated mitochondria was
      significantly less sensitive to mitochondrial calcium accumulation. Finally, 6
      weeks after transversal aortic constriction, Opa1(+/-) hearts demonstrated
      hypertrophy almost two-fold higher (P< 0.01) than in wild-type mice with altered
      ejection fraction (decrease in 43 vs. 22% in Opa1(+/+) mice, P< 0.05).
      CONCLUSIONS: These results suggest that, in adult cardiomyocytes, OPA1 plays an
      important role in mitochondrial morphology and PTP functioning. These properties
      may be critical for cardiac function under conditions of chronic pressure
      overload.

PMID- 22406750
TI  - Use of recipient's left colic artery for arterial reconstruction during liver
      transplantation in Alagille syndrome with vasculopathy: a case report.

PMID- 22406751
TI  - Additional evidence to support routine cytomegalovirus prophylaxis for all D+/R+
      renal graft recipients.

PMID- 22406749
TI  - Smooth muscle cell phenotypic switching in atherosclerosis.
AB  - Smooth muscle cells (SMCs) possess remarkable phenotypic plasticity that allows
      rapid adaptation to fluctuating environmental cues, including during development
      and progression of vascular diseases such as atherosclerosis. Although much is
      known regarding factors and mechanisms that control SMC phenotypic plasticity in
      cultured cells, our knowledge of the mechanisms controlling SMC phenotypic
      switching in vivo is far from complete. Indeed, the lack of definitive SMC
      lineage-tracing studies in the context of atherosclerosis, and difficulties in
      identifying phenotypically modulated SMCs within lesions that have down-regulated
      typical SMC marker genes, and/or activated expression of markers of alternative
      cell types including macrophages, raise major questions regarding the
      contributions of SMCs at all stages of atherogenesis. The goal of this review is
      to rigorously evaluate the current state of our knowledge regarding possible
      phenotypes exhibited by SMCs within atherosclerotic lesions and the factors and
      mechanisms that may control these phenotypic transitions.

PMID- 22406752
TI  - In vitro and in vivo proof of tolerance after two-step haploidentical bone marrow
      and kidney transplantation of the same donor.

PMID- 22406753
TI  - Inhibins and activins: towards the future. A tribute to the late Professor Wylie
      W. Vale.

PMID- 22406754
TI  - Atmospheric discharge and dispersion of radionuclides during the Fukushima Dai
      ichi Nuclear Power Plant accident. Part I: Source term estimation and local-scale
      atmospheric dispersion in early phase of the accident.
AB  - The atmospheric release of (131)I and (137)Cs in the early phase of the Fukushima
      Dai-ichi Nuclear Power Plant (FNPP1) accident from March 12 to 14, 2011 was
      estimated by combining environmental data with atmospheric dispersion simulations
      under the assumption of a unit release rate (1 Bq h(-1)). For the simulation,
      WSPEEDI-II computer-based nuclear emergency response system was used. Major
      releases of (131)I (>10(15) Bq h(-1)) were estimated when air dose rates
      increased in FNPP1 during the afternoon on March 12 after the hydrogen explosion
      of Unit 1 and late at night on March 14. The high-concentration plumes discharged
      during these periods flowed to the northwest and south-southwest directions of
      FNPP1, respectively. These plumes caused a large amount of dry deposition on the
      ground surface along their routes. Overall, the spatial pattern of (137)Cs and
      the increases in the air dose rates observed at the monitoring posts around FNPP1
      were reproduced by WSPEEDI-II using estimated release rates. The simulation
      indicated that air dose rates significantly increased in the south-southwest
      region of FNPP1 by dry deposition of the high-concentration plume discharged from
      the night of March 14 to the morning of March 15.

PMID- 22406755
TI  - Genome-wide analysis of long noncoding RNA stability.
AB  - Transcriptomic analyses have identified tens of thousands of intergenic,
      intronic, and cis-antisense long noncoding RNAs (lncRNAs) that are expressed from
      mammalian genomes. Despite progress in functional characterization, little is
      known about the post-transcriptional regulation of lncRNAs and their half-lives.
      Although many are easily detectable by a variety of techniques, it has been
      assumed that lncRNAs are generally unstable, but this has not been examined
      genome-wide. Utilizing a custom noncoding RNA array, we determined the half-lives
      of ~800 lncRNAs and ~12,000 mRNAs in the mouse Neuro-2a cell line. We find only a
      minority of lncRNAs are unstable. LncRNA half-lives vary over a wide range,
      comparable to, although on average less than, that of mRNAs, suggestive of
      complex metabolism and widespread functionality. Combining half-lives with
      comprehensive lncRNA annotations identified hundreds of unstable (half-life < 2
      h) intergenic, cis-antisense, and intronic lncRNAs, as well as lncRNAs showing
      extreme stability (half-life > 16 h). Analysis of lncRNA features revealed that
      intergenic and cis-antisense RNAs are more stable than those derived from
      introns, as are spliced lncRNAs compared to unspliced (single exon) transcripts.
      Subcellular localization of lncRNAs indicated widespread trafficking to different
      cellular locations, with nuclear-localized lncRNAs more likely to be unstable.
      Surprisingly, one of the least stable lncRNAs is the well-characterized
      paraspeckle RNA Neat1, suggesting Neat1 instability contributes to the dynamic
      nature of this subnuclear domain. We have created an online interactive resource
      (http://stability.matticklab.com) that allows easy navigation of lncRNA and mRNA
      stability profiles and provides a comprehensive annotation of ~7200 mouse
      lncRNAs.

PMID- 22406756
TI  - Electrophysiological responses to threat in youth with and without Posttraumatic
      Stress Disorder.
AB  - The current study was designed to examine event-related brain potentials and
      autonomic responses to pictures indicating threat, relative to non-threat, and
      acoustic startle reflexes in traumatized youth diagnosed with PTSD, relative to
      non-exposed children, before and after receiving psychotherapy. Children in the
      control group were individually yoked and demographically matched to the PTSD
      group. Both groups displayed enhanced late positive potentials and more prolonged
      heart rate deceleration to pictures indicating threat, relative to non-threat,
      and larger skin conductance responses to pictures indicating threat, relative to
      non-threat, at time one. At time two, controls appeared to habituate, as
      reflected by an overall attenuated skin conductance response, whereas the PTSD
      group showed little change. Across time points the PTSD group exhibited greater
      acoustic startle reflexes than the control group. Psychotherapy and symptom
      reduction was not associated with electrophysiology. Drawing from the adult
      literature, this study was an attempt to address the scarcity of research
      examining electrophysiological irregularities in childhood PTSD. The overall
      results suggest that children and adolescents allocate more attention to threat
      related stimuli regardless of PTSD status, and exaggerated startle and a possible
      failure to habituate skin conductance responses to threat-related stimuli in
      youth with versus without PTSD.

PMID- 22406757
TI  - Acute alcohol impairs human goal-directed action.
AB  - There are two forms of motivated behaviour. Goal-directed action is mediated by
      knowledge of the consequences whereas habitual action is elicited directly by
      stimuli associated with the action. Alcohol may impair goal-directed control,
      favouring habit. To evaluate this proposal, participants were administered with
      0.4 g/kg of alcohol or placebo before acquiring separate instrumental responses
      for chocolate and water points. Chocolate was then fed to satiety to devalue this
      outcome before choice between the two responses was tested in extinction. Any
      reduction in chocolate choice must be mediated by knowledge of the current
      incentive value of this outcome, i.e. must be goal-directed. Alcohol attenuated
      the devaluation effect on choice in extinction, but had no effect on
      reacquisition performance, the hedonic appraisal of rewards or acquisition of the
      instrumental contingencies. Acute alcohol impaired goal-directed control of
      action selection, favouring habit, which may mediate alcohol effects on under
      controlled behaviour more broadly.

PMID- 22406758
TI  - Stress hormones are associated with the neuronal correlates of instructed fear
      conditioning.
AB  - The effects of sex and stress hormones on classical fear conditioning have been
      subject of recent experimental studies. A correlation approach between basal
      cortisol concentrations and neuronal activation in fear-related structures seems
      to be a promising alternative approach in order to foster our understanding of
      how cortisol influences emotional learning. In this functional magnetic resonance
      imaging study, participants with varying sex hormone status (20 men, 15 women
      taking oral contraceptives, 15 women tested in the luteal phase) underwent an
      instructed fear conditioning protocol with geometrical figures as conditioned
      stimuli and an electrical stimulation as unconditioned stimulus. Salivary
      cortisol concentrations were measured and afterwards correlated with fear
      conditioned brain responses. Results revealed a positive correlation between
      basal cortisol levels and differential activation in the amygdala in men and OC
      women only. These results suggest that elevated endogenous cortisol levels are
      associated with enhanced fear anticipation depending on current sex hormone
      availability.

PMID- 22406759
TI  - An empirical model to predict the distribution of iron micro-particles around an
      injection well in a sandy aquifer.
AB  - The distribution of micro Fe particles injected into a porous medium via a well
      highly depends on flow velocity and slurry properties. Column experiments were
      conducted to predict the filtration behavior and, hence, the micro-iron
      distribution around a well. Packed-bed column experiments were conducted in
      different experimental conditions: seepage velocity, volume of injected
      suspension, iron particle and guar gum concentration (viscosity) were varied.
      Results are used to calculate a parameter "space removal efficiency"
      (eta(space)). Space removal efficiency is defined as the fraction of particle
      concentration lost by the slurry (and retained by the porous medium) while it
      crosses a unit length of the porous medium. eta(space) was found to be inversely
      proportional to seepage velocity and viscosity, while it is independent of the
      volume of injected slurry (or injection time) and particle concentration. The
      obtained relationships for eta(space) are used in an empirical numerical model to
      predict the distribution of iron particles around an injection well at a
      realistic field injection. To this purpose, the flow domain is discretized in
      shells, each characterized by a value of seepage velocity and by a distinct
      volume of slurry that flows through a unit of its surface. The resulting model,
      which is based on a large number of experimental observations (about 50 packed
      bed column tests), overcomes the limit of current approaches for predicting iron
      particle transport, as they consider mono-dimensional flow conditions, while
      during injection the flow field is radial. The proposed approach ought to help
      bridging the gap between laboratory scale research and the field scale
      application of micro-iron particle technology.

PMID- 22406760
TI  - BRCA1/2 mutations and expression: response to platinum chemotherapy in patients
      with advanced stage epithelial ovarian cancer.
AB  - OBJECTIVE: Our objective was to determine the rate of BRCA1/2 deficiency in
      platinum-sensitive and platinum-resistant tumors from a cohort of unselect
      patients with advanced epithelial ovarian cancer (EOH). METHODS: BRCA1/2 mutation
      analysis was performed in 29 patients with platinum-sensitive EOC and 24 patients
      with platinum-resistant disease. Germline DNA was analyzed in mutation carriers
      when normal tissue was available. BRCA expression was ascertained by quantitative
      rt-PCR. Associations between BRCA mutation status and expression levels and
      parameters of platinum response were analyzed. RESULTS: Fifteen of 53 (28.3%) EOC
      tumors had BRCA1/2 mutations. Twelve mutations were in BRCA1, while 3 involved
      BRCA2. Of the 12 mutation-carriers with normal tissue available for DNA analyses,
      33.3% of the mutations were found to be somatic. Three mutations were novel. The
      majority of BRCA mutations (73%) were identified in patients with platinum
      sensitive disease. In total, 38% of platinum-sensitive tumors were found to have
      a BRCA mutation, compared to 17% of the platinum-resistant patients. A
      statistical trend toward platinum-sensitive disease was seen in BRCA mutation
      carriers (p=0.079). Nineteen (36%) study patients had some form of BRCA
      deficiency, and these patients were less likely to have platinum-resistant tumors
      (OR=0.29; p value=0.048). CONCLUSIONS: BRCA mutations occurred more frequently in
      platinum-sensitive EOC than platinum-resistant disease. The high overall
      frequency of BRCA deficiency in EOC underscores the importance of tumor profiling
      as therapies targeting the DNA repair pathway are being investigated.

PMID- 22406761
TI  - [The fate of 20 sea breams. Mycobacterium marinum infection].
AB  - Cutaneous infections with Mycobacterium marinum are rare. They also are known as
      swimming pool or fish tank granulomas. Often the history of contact with
      contaminated water associated with microtrauma of the upper extremities leads to
      the correct diagnosis. Since chlorination of swimming pools has become standard,
      cases of swimming pool granuloma have become rare. Contact with fish tanks now is
      the most common route of infection. Positive culture of skin biopsy leads to the
      correct diagnosis. Moxifloxacin in combination with other antibiotics is often
      effective.

PMID- 22406762
TI  - [Tinea capitis profunda due to Trichophyton verrucosum with cMRSA superinfection
      in an infant].
AB  - A 28-month-old boy developed a cutaneous and subcutaneous lesion of the scalp
      together with alopecia. Treatment with sulfadiazine silver ointment and oral
      administration of cefaclor failed. The boy lived on a farm where cows and calves
      were present. He presented with a 5 cm erythematous, erosive, edematous, and
      sharply defined lesion with yellow crusts and circumscribed alopecia on the
      temporoparietal scalp. Peripheral hairs were easily epilated. Swabs from the
      wound revealed cMRSA (community acquired methicillin-resistant Staphylococcus
      aureus, Panton Valentine Leukocidin [PVL] toxin negative). There was no
      improvement after treatment with cefuroxime intravenously over 3 days. Therapy
      was changed to vancomycin and fosfomycin. Because of the purulent abscess,
      surgical incision was performed. PCR (polymerase chain reaction)-Elisa assay
      detected Trichophyton (T.) interdigitale-DNA from wound secretion and skin
      biopsy. Because of the clinical and molecular diagnosis of tinea capitis, oral
      antifungal therapy with fluconazole 5 mg kg(-1) body weight was started, along
      with cotrimoxazole and fosfomycin for the cMRSA. After 4 weeks incubation, the
      causative agent T. verrucosum was grown on culture and its identity confirmed by
      sequencing of the "internal transcribed spacer" (ITS) region of the ribosomal
      DNA. After 4 weeks of fluconazole, the lesion was nearly healed.

PMID- 22406763
TI  - [Charles Bukowski's acne].
AB  - In his autobiography, Charles Bukowski (1920-1994) describes his severe acne
      conglobata, his experience with therapy, family conflicts and emotional tension.
      Despite the stigmatization by his acne scars, Bukowski became a philobatic writer
      and a true chronist of the American way of life in the second half of the 20th
      century, writing in a coarse and obscene language.

PMID- 22406764
TI  - The reproductive system of Derocheilocaris typica (Crustacea, Mystacocarida).
AB  - Mystacocarids are dioecious. Their gonopores are on the medial side of the third
      thoracic limb. The male's paired testes lie in the thorax and abdomen. They
      develop from paired rows of six small follicles dorsally. In the mature animal
      they fill most of the abdomen. The spermatophores develop within the follicles
      from spermatogonia mixed with follicle cells, which support and nourish the
      spermatocytes and produce the seminal fluid. The short vas deferens runs along
      the bottom of the testes and then continues forward to the gonopore. The vas
      deferens has a small group of cells near the gonopore that becomes a closure
      mechanism. The female has reproductive cells and also support cells that provide
      nutrition and form the wall of the ovary and oviduct. The unpaired female ovary
      begins in the third thoracic segment. During maturation, the oocytes are pushed
      posteriorly. The enormous mature ovum extends into a caudal pocket of the ovary.
      Starting with its anterior end, this ovum is extruded into the short oviduct,
      which extends laterally and ventrally to the gonopore. During extrusion, the
      pocket is reabsorbed from behind. There are no accessory structures connected to
      the reproductive system, nor any external specializations on the third limb.

PMID- 22406765
TI  - Making decisions: the process of HIV disclosure for rural African American men.
AB  - The purpose of this study was to identify and describe the process of HIV
      disclosure for rural African American men-a population disproportionately
      affected by HIV/AIDS. Forty men were interviewed about their experience of making
      an HIV disclosure. Grounded theory methodology guided data collection and
      analysis. The core category or variable that emerged from the data was a process
      Making Decisions: The Process of HIV Disclosure. Five categories accounted for
      variations in disclosures: (a) beliefs and knowledge about HIV/AIDS, (b)
      influencing factors, (c) disclosure decisions, (d) disclosure efficacy, and (e)
      outcomes of disclosure. Most of the men had disclosed to others; however, the
      disclosures were selective, and the decisions were iterative. The majority of the
      men did not disclose their diagnosis for several months to several years. The
      findings provide a framework of the many factors related to HIV disclosure that
      can guide health care providers in counseling persons living with HIV/AIDS in
      making disclosure decisions.

PMID- 22406766
TI  - Hopelessness and sexual risk behavior among adolescent African American males in
      a low-income urban community.
AB  - African American youth bear a disproportionate burden of sexually transmitted
      infections. Environmental stressors may lead to increased hopelessness, which in
      turn can lead to increases in risk-taking behavior. This study explored the
      hypothesis that as hopelessness increases, sexual risk behavior will increase
      specifically, inconsistent condom use and increased number of sex partners. In
      2010, 108 African American men 15 to 24 years old responded to sexual behavior
      questions and Beck's Hopelessness Scale. The associations between hopelessness
      and sexual risk behaviors were evaluated with multivariate logistic regression.
      Increased hopelessness was associated with increased inconsistent condom use with
      non-main sexual partners (adjusted odds ratio = 2.3, 95% confidence interval =
      1.3-4.0). There was no association between hopelessness and condom use with a
      main partner or sex with more than one partner in the past 3 months. These
      findings imply that hopelessness may encourage sexual risk-taking behavior in
      young males.

PMID- 22406767
TI  - Advanced Drug Delivery Reviews (ADDR) is poised to embark on its second quarter
      of a century.

PMID- 22406768
TI  - Microfluidic diagnostics for the developing world.
AB  - For more than a decade, it has been expected that microfluidic technology would
      revolutionize the healthcare industry with simple, inexpensive, effective, and
      ubiquitous miniature diagnostic devices. To date, however, microfluidics has not
      yet been able to live up to these expectations. This fact has led to the recent
      development of new philosophies and methodologies for microfluidic diagnostics.
      In this Focus article, we will discuss some of the latest breakthroughs that
      could significantly impact medical diagnostics in the developing world.

PMID- 22406769
TI  - Quantitative proteomics and metabolomics approaches to demonstrate N-acetyl-D
      glucosamine inducible amino acid deprivation response as morphological switch in
      Candida albicans.
AB  - Candida albicans is a life threatening polymorphic pathogen for immunocompromised
      patients, causing superficial as well as invasive systemic diseases. The mucosal
      membranes of the host, which are the primary sites of its infection, are rich in
      amino sugars like N-acetylglucosamine (GlcNAc). GlcNAc is also one of the potent
      inducers of morphological transition, an important pathogenic trait of C.
      albicans. We thus performed proteomic analysis on total soluble proteins to
      identify the molecules involved in this response. Proteomic analysis using 2-DE
      demonstrated reproducible upregulation of 36 spots from a total of 585 matched
      spots. Mass spectroscopy (MS/MS) analyses of upregulated proteins revealed that
      carbohydrate and amino acid metabolism were the most prominent functional
      classes. Metabolite profiling using GC-MS allowed a quantitative comparison of 58
      metabolites in GlcNAc or glucose grown cells. We observed a significant decrease
      in the intracellular amino acid pool of GlcNAc grown cells. Moreover, GlcNAc
      induces both bZIP transcription factor (GCN4) and eIF2alpha kinase (GCN2) which
      are responsible for the activation of general amino acid control response in C.
      albicans. Inactivation of these genes blocks GlcNAc induced morphogenesis.
      Altogether these results suggest that amino acid starvation is the morphogenetic
      signal in presence of GlcNAc in C. albicans.

PMID- 22406770
TI  - The asymptomatic contralateral hip in unilateral slipped capital femoral
      epiphysis:  morbidity of prophylactic fixation.
AB  - Prophylactic contralateral fixation in unilateral slipped capital femoral
      epiphysis (SCFE) remains a controversial issue. In this study, 66 patients
      treated for unilateral SCFE (July 1997-April 2009) were screened for
      complications with need for surgical reintervention in the asymptomatic
      contralateral hip. Except for one patient, prophylactic fixation was performed in
      all cases. Major complications such as avascular necrosis were not seen; minor
      complications such as wound revision occurred in 4.6% (three of 65). In 16.9%
      (11/65) secondary loss of fixation with need for second fixation occurred. As the
      need for second fixation arose mostly bilaterally (10.7%, 7/65), only four
      patients (6.2%) required an additional surgical procedure for second fixation.
      Children who needed second fixation were significantly younger (11.8 years) than
      those who did not (13.1 years, P=0.013). In conclusion, this retrospective
      analysis shows that prophylactic contralateral fixation in SCFE is a safe
      procedure with no major complications and an acceptable rate of minor
      complications. When Kirschner wires are used for prophylactic pinning, there is a
      possibility of secondary loss of fixation due to length growth at the level of
      the physis. To avoid the need for secondary fixation, screw epiphysiodesis might
      be considered.

PMID- 22406771
TI  - Minocycline: the search for a community hospital acute stroke therapy.

PMID- 22406772
TI  - Genetics of intracerebral hemorrhage: Insights from candidate gene approaches.
AB  - Intracerebral hemorrhage (ICH) is a heterogeneous disease with genetic factors
      playing an important role. Association studies on a wide range of candidate
      pathways suggest a weak but significant effect for several alleles with ICH risk.
      Among the most widely investigated genes are those involved in the renin
      angiotensin-aldosterone system (e.g., angiotensin-converting enzyme), coagulation
      pathway (e.g., Factor XIII, Factor VII, platelet-activating factor
      acetylhydrolase, Factor V Leiden, and beta1-tubulin), lipid metabolism (e.g.,
      apolipoproteins (Apo)E, Apo(a), ApoH), homocysteine metabolism (e.g.,
      methylenetetrahydrofolate reductase), inflammation (e.g., interleukin-6 and tumor
      necrosis-alpha) and other candidate pathways. To identify the robustness of the
      above associations with ICH, a search of Pubmed (1988 through December 2011) was
      performed, with searches limited to English-language studies conducted among
      adult human subjects. This article presents a review of the examined literature
      on the genetics of ICH.

PMID- 22406773
TI  - Atlantoaxial dislocation.
AB  - Atlanto-axial dislocations (AADs) may be classified into four varieties depending
      upon the direction and plane of the dislocation i.e. anteroposterior, rotatory,
      central, and mixed dislocations. However, from the surgical point of view these
      are divided into two categories i.e. reducible (RAADs) and irreducible (IAADs).
      Posterior fusion is the treatment of choice for RAAD. Transarticular screw
      fixation with sub-laminar wiring is the most stable& method of posterior fusion.
      Often, IAAD is due to inadequate extension in dynamic X-ray study which may also
      be due to spasm of muscles. If the anatomy at the occipito-atlanto-axial region
      {O-C1-C2; O: occiput, C1: atlas, C2: axis} is normal on X-ray, the dislocation
      should be reducible. In case congenital anomalies at O-C1-C2 and IAAD are seen on
      flexion/extension studies of the cervical spine, the C1-C2 joints should be seen
      in computerized tomography scan (CT). If the C1-C2 joint facet surfaces are
      normal, the AAD should be reducible by cervical traction or during surgery by
      mobilizing the joints. The entity termed "dolichoodontoid" does not exist. It is
      invariably C2-C3 (C3- third cervical vertebra) fusion which gives an appearance
      of dolichoodontoid on plain X-ray or on mid-saggital section of magnetic
      resonance imaging (MRI) or CT scan. The central dislocation and axial
      invagination should not be confused with basilar invagination. Transoral
      odontoidectomy alone is never sufficient in cases of congenital IAAD, adequate
      generous three-dimensional decompression while protecting the underlying neural
      structures should be achieved. Chronic post-traumatic IAAD are usually Type II
      odontoid fractures which get malunited or nonunited with pseudoarthrosis in
      dislocated position. All these dislocations can be reduced by transoral removal
      of the offending bone, callous and fibrous tissue.

PMID- 22406774
TI  - Predictors of mortality in patients with meningeal tuberculosis.
AB  - BACKGROUND: Meningeal tuberculosis (TB) has higher mortality compared to other
      forms of central nervous system TB. However, data on predictors of mortality is
      limited. AIMS: To determine the predictors of mortality in patients with
      meningeal TB. MATERIALS AND METHODS: This study retrospectively analyzed the data
      of patients admitted with a diagnosis of meningeal TB between January 2006 and
      December 2008. Thwaites' index score of four or less was used for the diagnosis
      of meningeal TB which is a weighted diagnostic index score for dichotomised
      clinical variables. Predictors of mortality were analyzed separately for both
      patients with human immunodeficiency virus (HIV) infection and without.
      STATISTICAL ANALYSIS: Univariate analysis and multinomial logistic regression was
      done. RESULTS: Univariate analysis showed age >40 years, Glasgow Coma Scale (GCS)
      score <8, absence of headache, cerebrospinal fluid (CSF) protein <=60 mg% and
      Medical Research Council (MRC) Stage III at presentation to predict in-hospital
      mortality. In multinomial logistic regression age >40 years was a risk factor for
      mortality when HIV patients were included (P=0.049) as well as when they were
      excluded (P=0.048). CSF protein ? 60 mg% was found to be a significant risk
      factor when both HIV seropositive persons (P=0.011) as well as seronegative
      persons (P=0.004) were included. HIV seropositivity, steroid treatment or delay
      in treatment did not affect mortality. CONCLUSIONS: Identification of factors
      predictive of in-hospital mortality will help to prognosticate patients with
      meningeal TB at the time of admission.

PMID- 22406775
TI  - Efficacy of minocycline in acute ischemic stroke: a single-blinded, placebo
      controlled trial.
AB  - BACKGROUND: Minocycline is a semisynthetic derivative of the tetracycline group
      of antibiotics, which have neuroprotective effects. In animal stroke models,
      minocycline had shown promising evidence to improve clinical and functional
      outcomes. OBJECTIVE: To analyze the effect of oral minocycline in acute ischemic
      stroke patients. MATERIALS AND METHODS: This was a randomized single-blinded open
      label study. The study group received oral minocycline 200 mg/day for 5 days and
      the control group received oral vitamin B capsules. Baseline assessment included
      the following: National Institute of Health Stroke Scale (NIHSS) score, modified
      Barthel Index (mBI), modified Rankin Scale (mRS) score, Magnetic Resonance
      Imaging (MRI) of brain including Diffusion Weighted Imaging (DWI), chest X-ray,
      and routine laboratory investigations. The clinical scales were repeated at days
      1, 7, and 30. The end point was outcomes at 3 months (90 days). Statistical
      analysis was done with SPSS 11.5 (P<0.05). Paired t-test and multiple-measures
      Analysis Of Variance (ANOVA) were used. RESULTS: Fifty patients with acute
      ischemic stroke were included in the study. Of these, 23 patients received
      minocycline and 27 patients received placebo i.e., vitamin B capsules. NIHSS
      score in patients receiving minocycline had shown statistically significant
      improvement at day 30 and 90 as compared with the controls. Similarly, mRS scores
      and BI showed significant improvement in patients receiving minocycline at three
      months as compared to the control group. No mortality, myocardial infarctions,
      recurrent strokes, and hemorrhagic transformations were noted in both groups.
      CONCLUSIONS: Patients with acute ischemic stroke had significantly better outcome
      with minocycline treatment as compared with those administered placebo. The above
      findings suggest that minocycline can be helpful in reducing the clinical
      deficits after acute ischemic stroke.

PMID- 22406776
TI  - Hippocampal volume in children with temporal lobe epilepsy compared to healthy
      children: a magnetic resonance imaging study.
AB  - CONTEXT: There are currently few published studies that compare hippocampal
      volume (HCV) in children with temporal lobe epilepsy (TLE). Aims : T0 o compare
      HCVs in children with TLE and in relation to normal controls (NC), and to analyze
      HCV change in the acute phase in pediatric subjects using magnetic resonance
      imaging (MRI). Setting and Design : T0 he case group (n=24) was matched in gender
      and age range with NC subjects (n=24). Subjects were divided into three groups
      according to age: 2-5.9 years, 6-8.9 years and 9-13 years. MATERIALS AND METHODS:
      M0 anual measurements were used to obtain HCVs on oblique coronary MRI images
      obtained by three-dimensional magnetization-prepared rapid gradient-echo (3D
      MPRAGE) sequence. Statistical Analyses : T0 he HCV was calculated and normalized.
      Paired t-tests were used to compare the right and left HCVs within each study
      group. Analysis of covariance (ANCOVA) was used to consider the impact of age and
      gender on HCVs. RESULTS: T0 wenty-two patients were diagnosed with
      definite/probable TLE, and two were non-syndromic focal epilepsy which was
      distributed in the 2-5.9 years group. The range of left to right mean HCVs of the
      case and NC group aged 2-13 years was 2014.14 +/- 54.32 mm 3 to 2165.31 +/- 80.99
      mm 3 and 2015.46 +/- 26.97 mm 3 to 2100.93 +/- 57.33 mm 3 respectively. There
      were age-related differences in left and right HCV, but no effect of gender.
      Relative to NC subjects, cases group aged 2-5.9 years had significantly different
      HCVs, while no significant difference was found in the other two groups. There
      was significant difference in the right to left HCVs in the case subjects aged 2
      5.9 years, but not in the other age groups. CONCLUSIONS: T0 he heterogeneity in
      the 2-5.9 years age cohort may relate to the increased HCVs. The HCV data from NC
      subjects may be used as a reference to assess hippocampal abnormalities in
      clinical practice.

PMID- 22406777
TI  - The pattern of muscle involvement in ulnar neuropathy at the elbow.
AB  - OBJECTIVE: To determine the pattern of muscle involvement in patients with ulnar
      neuropathy at the elbow. MATERIALS AND METHODS: This study evaluated all patients
      referred for upper limb electrodiagnostic study (EDX) during 2007-2011 and
      included. patients with clinical signs and symptoms of ulnar neuropathy at the
      elbow. All patients had nerve conduction studies (NCS) for ulnar neuropathy.
      Needle electromyography (EMG) of four ulnar innervated muscles, flexor carpi
      ulnaris (FCU), flexor digitrom profoundus (FDP), first dorsal interosseous (FDI)
      and abductor digiti minimi (ADM)) was evaluated. RESULTS: During the study period
      34 (23 males and 11 females) patients were diagnosed with ulnar neuropathy at the
      elbow and three of them had bilateral involvement. Muscle involvement by EMG was
      as follows: FDI: 91.9%, ADM: 91.3%, FCU: 64.9% and FDP: 56.8%. CONCLUSION: In
      this study, EMG abnormalities of nerve damage were presented more commonly in the
      FCU muscle than in the FDP in patients with ulnar nerve lesion at the elbow.

PMID- 22406778
TI  - Validation of the Hindi version of National Institute of Health Stroke Scale.
AB  - AIMS: To determine the reliability and validity of the National Institute of
      Health Stroke Scale (NIHSS) with the Hindi and Indian adaptation of items 9 and
      10. MATERIALS AND METHODS: NIHSS items 9 and 10 were modified and culturally
      adapted at All India Institute of Medical Sciences (AIIMS) and the resulting
      version was termed as Hindi version (HV-NIHSS). HV-NIHSS was applied by two
      independent investigators on 107 patients with stroke. Inter-observer agreement
      and intra-class correlation coefficients were calculated. The predictive validity
      of the HV-NIHSS was calculated using functional outcome after three months in the
      form of modified Rankin Scale (mRS) and Barthel Index (BI). RESULTS: The study
      included 107 patients of stroke recruited from a tertiary referral hospital at
      Delhi between November 1, 2009, and October 1, 2010; the mean age of these
      patients was 56.26+/-13.84 years and 65.4% of them had suffered ischemic stroke.
      Inter-rater reliability was high between the two examiners, with Pearson's r
      ranging from 0.72 to 0.99 for the 15 items on the Scale. Intra-class correlation
      coefficient for the total score was 0.995 (95% CI-0.993-0.997). Concurrent
      construct validity was established between HV-NIHSS and baseline Glasgow Coma
      Scale, with a high correlation (Spearman coefficient = -0.863, P<.001).
      Predictive validity was also established with BI at three months (Spearman's rho:
      -0.829, P<.001) and with mRS at three months (Spearman's rho: 0.851, P<0.001).
      CONCLUSIONS: This study shows that a Hindi language version of the NIHSS
      developed at AIIMS appears reliable and valid when applied to a Hindi-speaking
      population.

PMID- 22406779
TI  - Fenestrations accompanied by intracranial aneurysms assessed with magnetic
      resonance angiography.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to evaluate the anatomical
      changes and investigate the prevalence in intracranial aneurysm with
      fenestrations using magnetic resonance angiography (MRA). MATERIALS AND METHODS:
      Between June 2008 and October 2010, 4652 patients (aged 23-73 years) with
      suspected intracranial aneurysm or other cerebrovascular diseases underwent MRA
      examination. MRA was performed using a three-dimensional time-of-flight technique
      (3D-TOF) with volume rendering (VR) and maximum intensity projection
      reconstruction methods. The presence and location of fenestrations and aneurysms
      was reviewed. When fenestrations were present in combination with aneurysms, we
      noted the relationship of the locations. The classification of fenestration
      accompanied by intracranial aneurysm was divided into three types according to
      the anatomical relationship as follows: Type I, aneurysm adjacent to but not on a
      fenestration; Type II, aneurysm located on the fenestration; type III, aneurysm
      located at a position remote from a fenestration. RESULTS: Among the 4652
      patients examined, 409 patients were defined with 412 intracranial aneurysms, and
      the prevalence of aneurysms was 8.8%. One hundred and forty-one patients were
      identified with fenestrations; 24 of these patients were confirmed with
      intracranial aneurysms. Seven cases were classified as type I, three as type II
      and 14 as type III. The prevalence of intracranial aneurysm with fenestrations
      was 17.0%, with significant statistical difference compared with aneurysms
      unaccompanied with fenestrations (P=0.0064). CONCLUSION: The anatomical
      relationship between fenestrations and intracranial aneurysms was visualized by
      MRA with VR, which displayed pathologies with sufficient clarity to enable
      diagnosis. Furthermore, the results of this study suggest that physicians should
      be alerted to the occurrence of intracranial aneurysm following the detection of
      fenestrations by MRA.

PMID- 22406780
TI  - Does bony hyperostosis in intracranial meningioma signify tumor invasion? A radio
      pathologic study.
AB  - BACKGROUND: While operating intracranial meningiomas, neurosurgeons commonly
      drill the hyperostotic bone and put the bone flap back. OBJECTIVE: To determine
      whether bony changes seen in meningioma are due to tumor invasion or reactionary
      changes. MATERIALS AND METHODS: This prospective study, conducted over 10 months
      (October 2010- July 2011) included consecutive patients with intracranial
      meningiomas. Preoperatively, computed tomography (CT) was done in all patients
      and reviewed by two neurosurgeons for associated bony hyperostosis. During
      surgery, a piece of bone showing hyperostosis was taken for histopathological
      evaluation for tumor invasion. In absence of hyperostosis, the bone sample was
      taken from the bone in contact with the dural attachment of the tumor. RESULTS:
      This study included 40 consecutive patients who underwent resection for
      intracranial meningiomas. Radiological evidence of hyperostosis was present in 30
      (75%) patients. On histopathological examination, tumor invasion of the bone was
      seen in eight (20%) patients. These included seven patients who demonstrated
      hyperostosis and one patient without hyperostosis. Convexity meningiomas (n=12)
      showed the highest rate of bony invasion (33.3%). CONCLUSIONS: A significant
      number of patients with radiological hyperostosis have tumor invasion of the
      bone. The authors recommend that one should remove the bone (flap) whenever
      possible in order to achieve total excision of the tumor and use synthetic
      material to cover the defect.

PMID- 22406781
TI  - Endovascular treatment of complicated ruptured anterior communicating artery
      aneurysms based on the anatomical features of the anterior communicating artery
      complex.
AB  - BACKGROUND: Endovascular therapy of complicated ruptured anterior communicating
      artery (ACoA) aneurysms is difficult due to their small size and unfavorable
      shape. AIM: Based on the anatomical features of the ACoA complex, we investigated
      the feasibility and efficacy of different coil embolism strategies for
      complicated ACoA aneurysms. MATERIALS AND METHODS: Sixteen patients with
      complicated ruptured ACoA aneurysms received endovascular treatment. Aneurysm sac
      plus ACoA embolism or ACoA coil embolism were performed if the bilateral A1
      segment was normally developed or unilateral A1 segment dysplasia (>=1/2 normal
      contralateral diameter) was present. Where unilateral A1 segment dysplasia (<1/2
      normal contralateral diameter) or aplasia was present, sac embolism alone was
      performed. Follow-up angiography was performed, and clinical follow-up data were
      categorized as fully recovered, improved, unchanged or worsened. RESULTS:
      Aneurysm sac plus ACoA (n=5) or ACoA alone (n=2) coil embolism was performed in
      seven patients with normal bilateral A1 segments (n=5) or dysplasia (n=2). Sac
      coil embolism was performed in nine patients with unilateral A1 segment dysplasia
      (n=1) or aplasia (n=8). Immediate angiography indicated total/near-total
      occlusion was achieved in 14 patients. Final angiographic (mean 11.9 +/- 5.1
      months) and clinical (mean 17.7 +/- 5.9 months) follow-up confirmed total/near
      total occlusion in 12 patients, one partial occlusion, two enlarged residual sacs
      and one reopened aneurysm. Clinical symptoms fully recovered in 10 patients,
      improved in four, were unchanged in one and worsened in one patient. CONCLUSION:
      This small middle-term follow-up study demonstrates coil embolism endovascular
      treatment of complicated ruptured ACoA aneurysms, based on the anatomical
      features of the ACoA complex, is feasible and effective.

PMID- 22406782
TI  - Concordance between local, institutional, and central pathology review in
      glioblastoma: implications for research and practice: a pilot study.
AB  - BACKGROUND: There is significant inter-observer variation amongst the neuro
      pathologists in the typing, subtyping, and grading of glial neoplasms for
      diagnosis. Centralized pathology review has been proposed to minimize this inter
      observer variation and is now almost mandatory for accrual into multicentric
      trials. We sought to assess the concordance between neuro-pathologists on
      histopathological diagnosis of glioblastoma. MATERIALS AND METHODS: Comparison of
      local, institutional, and central neuro-oncopathology reporting in a cohort of 34
      patients with newly diagnosed supratentorial glioblastoma accrued consecutively
      at a tertiary-care institution on a prospective trial testing the addition of a
      new agent to standard chemo-radiation regimen. RESULTS: Concordance was sub
      optimal between local histological diagnosis and central review, fair between
      local diagnosis and institutional review, and good between institutional and
      central review, with respect to histological typing/subtyping. Twelve (39%) of 31
      patients with local histological diagnosis had identical tumor type, subtype and
      grade on central review. Overall agreement was modestly better (52%) between
      local diagnosis and institutional review. In contrast, 28 (83%) of 34 patients
      had completely concordant histopathologic diagnosis between institutional and
      central review. The inter-observer reliability test showed poor agreement between
      local and central review (kappa statistic=0.12, 95% confidence interval (CI): 
      0.03-0.32, P=0.043), but moderate agreement between institutional and central
      review (kappa statistic=0.51, 95%CI: 0.17-0.84, P=0.00003). Agreement between
      local diagnosis and institutional review was fair. CONCLUSIONS: There exists
      significant inter-observer variation regarding histopathological diagnosis of
      glioblastoma with significant implications for clinical research and practice.
      There is a need for more objective, quantitative, robust, and reproducible
      criteria for better subtyping for accurate diagnosis.

PMID- 22406783
TI  - Narcolepsy: past, present and future.

PMID- 22406784
TI  - Sleep-related disorders among a healthy population in South India.
AB  - INTRODUCTION: Sleep-related disorders (SRDs) though frequent, are under-reported
      and their implications are often neglected. OBJECTIVE: To estimate SRDs in an
      apparently healthy South Indian population. MATERIALS AND METHODS: Data was
      collected by administering a questionnaire including Sleep Disorders Proforma,
      Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index (PSQI) to 1050
      apparently healthy attendants/relatives of patients attending a tertiary
      healthcare institution. RESULTS: The mean age of the respondents was 35.1+/-8.7
      years with even gender distribution (male: female; 29:21), work hours were 7.8+/
      1.33 h and had regional representation from the southern Indian states. The
      majority of the respondents did not report any significant medical/psychiatric co
      morbidities, hypertension was noted in 42.6%, in one-fourth, the body mass index
      (BMI) was >25, and in 7.7% the neck size was >40 cm. Daily tea (70.3%) and coffee
      (17.9%) consumption was common and 22.2% used tobacco. Average time-to-fall
      asleep was 22 min (range: 5-90 min), average duration-of-actual-sleep was 7 h
      (range: 3.5-9.1 h) with the majority (93.8%) reporting good-quality sleep (global
      PSQI <=5). The reported rates of SRDs varied between 20.0% and 34.2% depending on
      the instrument used in the questionnaire. Insomnia, sleep-related breathing
      disorders (SRBD), narcolepsy, and restless legs syndrome (RLS) were reported by
      18.6%, 18.4%, 1.04% and 2.9%, respectively. Obesity was not strongly associated
      with SRBD. in 51.8% of subjects with SRBD BMI was <25 kg/m 2 . Of the respondents
      with insomnia, 18% had difficulty in initiating sleep, 18% in maintaining sleep
      and 7.9% had early morning awakening. Respondents attributed insomnia to
      depression (11.7%) or anxiety (2.5%). Insomnia was marginally high in females
      when compared to males (10.3% vs. 8.3%) and depression was the major reason. RLS,
      which was maximal at night, was responsible for delayed sleep onset (74.2%).
      Other SRDs included night terrors (0.6%), nightmares (1.5%), somnambulism (0.6%),
      and sleep-talking (2.6%). Family history of SRDs was present in 31.4%
      respondents. While, only 2.2% of the respondents self-reported and acknowledged
      having SRD, health-seeking was extremely low (0.3%). CONCLUSION: SRDs are widely
      prevalent in India. Considering the health implications and poor awareness, there
      is a need to sensitize physicians and increase awareness among the public.

PMID- 22406785
TI  - Clinical and polysomnographic characteristics in 20 North Indian patients with
      narcolepsy: a seven-year experience from a neurology service sleep clinic.
AB  - BACKGROUND: Narcolepsy is not an uncommon sleep disorder in the West. There is,
      however, only one reported case in literature from India. In this study, we
      report characteristics of patients with narcolepsy over a seven-year period.
      MATERIALS AND METHODS: Details of all patients with narcolepsy seen at a Sleep
      Disorders Clinic over seven years were analyzed. Diagnosis had been established
      by clinical history and two or more Sleep Onset Rapid Eye Movement Periods
      (SOREMPs) on Multiple Sleep Latency Test (MSLT) following an overnight
      Polysomnography (PSG), using the International Classification of Sleep Disorders 
      2 (ICSD-2) criteria. Patients fulfilling the criteria, but suffering from other
      disorders were excluded. RESULTS: Data of 20 patients were analyzed and 4
      patients were excluded, as they had other associated conditions. Mean age at
      onset of symptoms was 25+/-10 years; 12 (60%) patients had narcolepsy with
      cataplexy, 4 (20%) patients presented with all cardinal symptoms of narcolepsy, 8
      (40%) with 3 symptoms, while 8 (40%) presented with 2 symptoms. History of
      Excessive Day-Time Sleepiness (EDS) was present in all patients. Three patients
      reported accidents due to sleep attacks, one being life-threatening. On PSG, mean
      sleep efficiency was 79.4+/-12.40%. Mean sleep latency during MSLT was 1.30
      minute (range: 0.30-2.30 minute) and mean REM latency was 2.58+/-0.64 minute.
      CONCLUSION: Narcolepsy with and without cataplexy is infrequently seen in the
      North Indian population; however, clinical and polysomnographic features are
      similar to those observed in Western and other Asian populations.

PMID- 22406786
TI  - Narcolepsy: a case from India with polysomnographic findings.
AB  - Narcolepsy is a common sleep disorder with a prevalence of about 0.02%. However,
      it may remain largely unrecognized in the Indian population owing to the
      perceived low prevalence. To the best of our knowledge there is only one case of
      narcolepsy reported from India so far. We present a case of narcolepsy with
      cataplexy with classical clinical and polysomnographic findings of narcolepsy.

PMID- 22406787
TI  - Analysis of the genotype of diacylglycerol kinase delta single-nucleotide
      polymorphisms in Parkinson disease in the Han Chinese population.
AB  - Numerous Single-Nucleotide Polymorphisms (SNPs) of the Diacylglycerol Kinase
      Delta (DGKD) isoform 1 gene have been associated with Parkinson Disease (PD) in
      the genome-wide association studies of Caucasian population. This association has
      not been proven in the Han Chinese PD patients. This study included 376 unrelated
      Han Chinese PD patients from West China and 273 unrelated healthy controls from
      the same region. Five SNPs (rs2971859, rs1550532, rs2305539, rs2034762, and
      rs2242102) were genotyped using the Sequenom iPLEX Assay technology. No
      significant differences were observed in genotype frequencies and in the Minor
      Allele Frequency (MAF) in the five SNPs between PD patients and controls, early
      onset PD and controls, late-onset PD and controls, and between early-onset and
      late-onset PD patients. The present study is the first to report on the lack of
      association of DGKD SNPs with PD in the Han Chinese population. More related
      studies involving larger numbers of participants are necessary to confirm the
      present finding.

PMID- 22406788
TI  - A study of familial MELAS: evaluation of A3243G mutation, clinical phenotype, and
      magnetic resonance spectroscopy-monitored progression.
AB  - The clinical manifestations of mitochondrial myopathy, encephalopathy, lactic
      acidosis, and stroke-like episodes syndrome (MELAS syndrome) are nonspecific and
      can easily be misdiagnosed. Magnetic resonance spectroscopy (MRS)-based detection
      of lactate in the brain has been found to be of diagnostic help in MELAS
      syndrome, however, the issue of whether MRS features vary by stage remains
      unresolved. We assessed the causative mutation and radiological features of a
      family of MELAS. Four of the family members harbored the A3243G mutation,
      probably of maternal inheritance. However, the clinical phenotypic expression was
      different in these patients. MRS showed a lactate peak, decreased N
      acetylaspartate, choline, and creatine, which became more pronounced with
      progression of the disease, demonstrating that brain-MRS-based detection of
      lactate may be a suitable way to monitor the progression and treatment of MELAS.

PMID- 22406789
TI  - Atypical presentation of pediatric mixed germ cell tumors in the sellar
      suprasellar region.
AB  - Intracranial germ cell tumors constitute a unique group of tumors, more often
      reported from the Asian region. Amongst them, the non-germinomatous variety
      occurs with a lesser frequency than the germinomatous variety. We report two
      children with mixed germ cell tumors with unusual clinical presentations: Central
      diabetes insipidus and recent-onset oculomotor palsy mimicking pituitary
      apoplexy. Unlike in adults, suprasellar lesions with a pituitary apoplexy-like
      picture in the pediatric age group may suggest a possibility of a mixed germ cell
      tumor.

PMID- 22406790
TI  - Dural arteriovenous fistula of crianiocervical junction: Four case reports.
AB  - The clinical characteristics of aggressive craniocervical junction dural
      arteriovenous fistula (CCJDAVF) and effect treatment was studied in four patients
      and all four patients were treated endovascularly with liquid embolic agents.
      Post-embolization angiography documented complete obliteration in one patient and
      partial obliteration in the other three patients. All patients had good recovery
      without any procedure-related complications. Endovascular embolization can be
      used to reduce the rate of flow through CCJDAVFs or as a definitive treatment
      when the fistula is accessible endovascularly.

PMID- 22406791
TI  - Embryonal tumor with multilayered rosettes: Two case reports with a review of the
      literature.
AB  - Embryonal tumor with multilayered rosettes (ETMR) is a well-recognized
      histopathological variant of primitive neurectodermal tumors of the central
      nervous system. This tumor depicts histopathological features that are common to
      both ependymoblastoma (EBL) and neuroblastoma. Here we report two pediatric cases
      of ETMR, one exhibiting dominant neuronal differentiation and the other with
      dominant glial differentiation, thereby expanding the previously known pathologic
      spectrum. The varying histological features, common morphologic diagnostic
      difficulties as well as variable postsurgical survival of this entity compared to
      similar embryonal tumors are highlighted.

PMID- 22406792
TI  - Fat embolism syndrome mimicker of diffuse axonal injury on magnetic resonance
      imaging.

PMID- 22406793
TI  - Sparganosis of the cauda equina: a rare case report and review of the literature.

PMID- 22406794
TI  - Association of unilocular thymic cyst and myasthenia gravis.

PMID- 22406795
TI  - A fatal combo of dengue shock syndrome with acute subdural hematoma.

PMID- 22406796
TI  - Massive vasculitic cerebellar infarction in patient with systemic lupus
      erythematosus.

PMID- 22406797
TI  - Vertebral artery dissection and intractable hiccups: an uncommon presentation.

PMID- 22406798
TI  - "Wine-glass appearance" of pyramidal tracts in a patient with primary lateral
      sclerosis.

PMID- 22406799
TI  - Supratentorial extra-axial anaplastic ependymoma mimicking a meningioma.

PMID- 22406800
TI  - Aneurysmal bone cyst of cervical spine: true 360 degrees  resection with emphasis
      on lateral masses.

PMID- 22406801
TI  - Primary intracranial multicentric angioleiomyomas.

PMID- 22406802
TI  - Foramen magnum extramedullary cavernous hemangioma in a pediatric patient.

PMID- 22406803
TI  - Endovascular management of carotid-cavernous fistula in Ehlers-Danlos syndrome
      Type IV.

PMID- 22406804
TI  - Intraparenchymal mesenchymal chondrosarcoma in an unusual location.

PMID- 22406805
TI  - Intramedullary arachnoid cyst: report of two cases.

PMID- 22406806
TI  - Cervicomedullary compression secondary to proliferation of transverse atlantal
      ligament.

PMID- 22406807
TI  - Giant pediatric aneurysmal bone cyst of the occipital bone: case report and
      review of the literature.

PMID- 22406808
TI  - Subarachnoid hemorrhage from a ruptured proximal lenticulostriate artery
      aneurysm.

PMID- 22406809
TI  - Dorsally placed extradural infected neurenteric cyst in a two-year old with
      paraspinal extension.

PMID- 22406810
TI  - An anaplastic ependymoma presenting as an intrinsic brainstem glioma.

PMID- 22406811
TI  - Angiosarcoma presenting as subdural hematoma.

PMID- 22406812
TI  - Giant thoracolumbar intradural multilobulated arachnoid cyst.

PMID- 22406813
TI  - Dilated Virchow Robin spaces mimicking cystic neoplasm of cingulated gyrus.

PMID- 22406814
TI  - Copper ion liquid-like thermoelectrics.
AB  - Advanced thermoelectric technology offers a potential for converting waste
      industrial heat into useful electricity, and an emission-free method for solid
      state cooling. Worldwide efforts to find materials with thermoelectric figure of
      merit, zT values significantly above unity, are frequently focused on crystalline
      semiconductors with low thermal conductivity. Here we report on Cu(2-x)Se, which
      reaches a zT of 1.5 at 1,000 K, among the highest values for any bulk materials.
      Whereas the Se atoms in Cu(2-x)Se form a rigid face-centred cubic lattice,
      providing a crystalline pathway for semiconducting electrons (or more precisely
      holes), the copper ions are highly disordered around the Se sublattice and are
      superionic with liquid-like mobility. This extraordinary 'liquid-like' behaviour
      of copper ions around a crystalline sublattice of Se in Cu(2-x)Se results in an
      intrinsically very low lattice thermal conductivity which enables high zT in this
      otherwise simple semiconductor. This unusual combination of properties leads to
      an ideal thermoelectric material. The results indicate a new strategy and
      direction for high-efficiency thermoelectric materials by exploring systems where
      there exists a crystalline sublattice for electronic conduction surrounded by
      liquid-like ions.

PMID- 22406816
TI  - On the temperature dependence of ballistic Coulomb drag in nanowires.
AB  - We have investigated within Fermi liquid theory the dependence of Coulomb drag
      current in a passive quantum wire on the applied voltage V across an active wire
      and on the temperature T for any values of eV/k(B)T. We assume that the bottoms
      of the 1D minibands in both wires almost coincide with the Fermi level. We
      conclude that: (1) within a certain temperature interval the drag current can be
      a descending function of the temperature T; (2) the experimentally observed
      temperature dependence T(-0.77) of the drag current can be interpreted within the
      framework of Fermi liquid theory; (3) at relatively high applied voltages the
      drag current saturates as a function of the applied voltage; and (4) the
      screening of the electron potential by metallic gate electrodes can be of
      importance.

PMID- 22406815
TI  - MiR-217 is involved in Tat-induced HIV-1 long terminal repeat (LTR)
      transactivation by down-regulation of SIRT1.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and
      may contribute to the development and progression of many infective diseases
      including human immunodeficiency virus 1 (HIV-1) infection. The Tat protein is
      fundamental to viral gene expression. In this study, our goal was to investigate
      the regulation of a specific miRNA (known as miR-217) in multinuclear activation
      of galactosidase indicator (MAGI) cells and explore the mechanisms by which miR
      217 influenced Tat-induced HIV-1 transactivation through down-regulation of SIRT1
      expression. We showed that miR-217 was up-regulated when Tat was expressed in
      multinuclear activation of galactosidase indicator cells. Forced expression of
      "miR-217 mimics" increased Tat-induced LTR transactivation. In addition, miR-217
      significantly inhibited SIRT1 protein expression by acting on the 3'-UTR of the
      SIRT1 mRNA. In turn, the decrease in SIRT1 protein abundance provoked by miR-217
      affected two important types of downstream signaling molecules that were
      regulated by Tat. Lower expression of SIRT1 caused by miR-217 enhanced Tat
      induced phosphorylation of IKK and p65-NFkB and also exacerbated the loss of AMPK
      phosphorylation triggered by Tat. Our results uncover previously unknown links
      between Tat and a specific host cell miRNA that targets SIRT1. We also
      demonstrate that this regulatory mechanism impinges on p65-NFkB and AMPK
      signaling: two important host cell pathways that influence HIV-1 pathogenesis.
      Our results also suggest that strategies to augment SIRT1 protein expression by
      down-regulation of miR-217 may have therapeutic benefits to prevent HIV-1
      replication.

PMID- 22406817
TI  - Diverse functions of uterine proteoglycans in human reproduction (review).
AB  - Proteoglycans (PGs) are a group of heavily glycosylated proteins that are present
      throughout the mammalian body and are involved in a wide variety of biological
      phenomena, including structural maintenance, tissue remodeling, molecular
      presentation, cell adhesion and signal transmission. Previous studies have
      revealed an increasing number of roles for PGs in human reproduction. Several PGs
      are currently utilized or regarded as biomarkers for the diagnosis of certain
      pathological uterine conditions associated with infertility and obstetrical
      complications. The aim of this review was to discuss the involvement of PGs in
      the human uterus in reproductive biology and pathophysiology.

PMID- 22406818
TI  - Allocation of vascularized composite allografts:  what is it?
AB  - To date, there are more than 80 reports of vascularized composite allografts
      (VCAs; a.k.a. composite tissue allotransplantation). However, the classification
      of this type of transplantation for oversight purposes has not been clarified.
      From a biological and regulatory perspective, we propose that VCA retrieval and
      transplantation is akin to organ transplantation and should be incorporated into
      the organ oversight structure. As VCA becomes more of a clinical reality, the
      need for a methodical approach to allocation and access to more donors will
      develop. Such an allocation system will likely incorporate parameters that
      deviate from those used for organ transplantation. To develop an effective and
      balanced system, the use of existing regulatory agencies that oversee solid
      organs should provide the maximum benefit to the patients and the society.

PMID- 22406819
TI  - Association of cytomegalovirus infection and disease with recurrent hepatitis C
      after liver transplantation.
AB  - BACKGROUND: Cytomegalovirus (CMV) has been inconsistently associated with
      recurrent hepatitis C virus (HCV) after liver transplant (LT). METHODS: A
      retrospective study of 347, donor or recipient CMV seropositive, first LT
      recipients transplanted for HCV was performed to evaluate the associations of CMV
      infection and disease occurring within 1-year of LT with the primary endpoints of
      allograft inflammation grade >=2 and fibrosis stage >=2. Associations were
      evaluated using multivariable Cox regression models. RESULTS: CMV infection and
      disease occurred in 111 (32%) and 24 (7%) patients, respectively. Hepatic
      allograft inflammation grade >=2 and fibrosis stage >=2 occurred in 221 (64%) and
      140 (40%) patients, respectively. CMV infection was associated with increased
      risk of fibrosis stage >=2 (relative risk [RR], 1.52; P=0.033). CMV disease was
      associated with increased risk of inflammation grade >=2 (RR, 3.40; P<0.001), and
      although not significant, with fibrosis stage >=2 (RR, 2.03; P=0.052). These
      associations did not differ significantly according to recipient CMV
      seropositivity. CONCLUSIONS: Our results support an association between CMV
      infection and disease with recurrence of HCV after LT. Investigation of
      prevention of CMV infection and disease as a strategy to mitigate recurrent HCV
      in LT recipients is warranted.

PMID- 22406820
TI  - Regulation of endothelial and hematopoietic development by the ETS transcription
      factor Etv2.
AB  - PURPOSE OF REVIEW: Vasculogenesis and hematopoiesis are essential for
      development. Recently, the ETS domain transcription factor Etv2 has been
      identified as an essential regulator of vasculogenesis and hematopoiesis. Here,
      we review the recent studies that have established the critical role of Etv2 in
      the specification of mesoderm to blood and endothelial cells. RECENT FINDINGS:
      Loss and gain-of-function studies have demonstrated the conserved role of Etv2 in
      endothelial and hematopoietic development. Recent studies have placed Etv2 at or
      near the top of the hierarchy in specification of these lineages and have begun
      to dissect the upstream regulators and downstream effectors of Etv2 function
      using multiple model organisms and experimental systems. SUMMARY: Etv2 is
      essential for the specification of endothelial and hematopoietic lineages.
      Understanding the mechanisms through which Etv2 specifies endothelial and blood
      cells by defining upstream transcriptional regulators and cofactors will lead to
      greater insight into vasculogenesis and hematopoiesis, and may help to identify
      therapeutic targets to treat vascular disorders or to promote or inhibit vessel
      growth.

PMID- 22406822
TI  - Integration of experimental and computational approaches to sprouting
      angiogenesis.
AB  - PURPOSE OF REVIEW: We summarize recent experimental and computational studies
      that investigate molecular and cellular mechanisms of sprouting angiogenesis. We
      discuss how experimental tools have unveiled new opportunities for computational
      modeling by providing detailed phenomenological descriptions and conceptual
      models of cell-level behaviors underpinned by high-quality molecular data. Using
      recent examples, we show how new understanding results from bridging
      computational and experimental approaches. RECENT FINDINGS: Experimental data
      extends beyond the tip cell vs. stalk cell paradigm, and involves numerous
      molecular inputs such as vascular endothelial growth factor and Notch. This data
      is being used to generate and validate computational models, which can then be
      used to predict the results of hypothetical experiments that are difficult to
      perform in the laboratory, and to generate new hypotheses that account for system
      wide interactions. As a result of this integration, descriptions of critical
      gradients of growth factor-receptor complexes have been generated, and new
      modulators of cell behavior have been described. SUMMARY: We suggest that the
      recent emphasis on the different stages of sprouting angiogenesis, and
      integration of experimental and computational approaches, should provide a way to
      manage the complexity of this process and help identify new regulatory paradigms
      and therapeutic targets.

PMID- 22406821
TI  - MicroRNA regulation of smooth muscle gene expression and phenotype.
AB  - PURPOSE OF REVIEW: In this review, we summarize the recent advances regarding
      microRNA (miRNA) functions in the regulation of vascular smooth muscle cell
      (VSMC) differentiation and phenotypic modulation. RECENT FINDINGS: Multiple
      miRNAs are found to be responsible for VSMC differentiation and proliferation
      under physiological or pathological condition. A single miRNA downregulates
      multiple targets, whereas a single gene is regulated by multiple miRNAs to
      modulate a specific aspect of VSMC phenotype. SUMMARY: The phenotype of VSMCs is
      dynamically regulated in response to environmental stimuli. Deregulation of
      phenotype switching is associated with vascular diseases. Several miRNAs have
      been found to be highly expressed in the vasculature, to modulate VSMC phenotype,
      and to be dysregulated in vascular diseases. By regulating mRNA and/or protein
      levels posttranscriptionally, miRNAs provide a delicate regulation in the complex
      molecular networks that regulate the vascular system. Understanding the functions
      of miRNAs in the regulation of VSMC differentiation and phenotype switching
      provides new insights into the mechanisms of vascular development, function, and
      dysfunction.

PMID- 22406823
TI  - Ex-vivo generation of human red cells for transfusion.
AB  - PURPOSE OF REVIEW: The present article reviews the recent data concerning the
      generation of red blood cells from haematopoietic stem cells using laboratory
      culture and discusses the potential for generating cultured red cells in
      sufficient quantity for use in transfusion practice. RECENT FINDINGS: Functional
      human reticulocytes have been generated from adult peripheral blood
      haematopoietic stem cells in laboratory culture without the use of heterologous
      feeder cells and their viability was demonstrated in vivo. Human erythroid
      progenitor cells lines have been produced from cord and human induced pluripotent
      stem cell (hiPSC) haematopoietic progenitors. SUMMARY: Availability of cultured
      human red cells from haematopoietic stem cells in the quantities required for
      transfusion therapy would have a major impact on healthcare provision worldwide.
      Recent studies provide cause for optimism that this ambitious goal is achievable.
      Functional adult reticulocytes have been made in culture and shown to survive in
      vivo. Erythroid progenitor cell lines have been derived from cord blood and from
      human induced pluripotent stem cells, suggesting that large-scale culture of
      erythroid cell lines and their differentiation to reticulocytes will be possible.
      Significant problems remain. More efficient enucleation and induction of
      maturation to an adult phenotype will be required in order to exploit high
      proliferative capacity of human embryonic stem cells and hiPSCs. Novel
      bioengineering solutions will be required to generate cultured red cells in the
      large quantities required, and in this context, use of synthetic three
      dimensional scaffolds to mimic the bone marrow niche holds great promise for the
      future.

PMID- 22406824
TI  - Heme metabolism and erythropoiesis.
AB  - PURPOSE OF REVIEW: Heme biosynthesis requires a series of enzymatic reactions
      that take place in the cytosol and the mitochondria as well as the proper
      intercellular and intracellular trafficking of iron. Heme can also be acquired by
      intestinal absorption and intercellular transport. The purpose of this review is
      to highlight recent work on heme and iron transport with an emphasis on their
      relevance in erythropoiesis. RECENT FINDINGS: Whereas the enzymes responsible for
      heme biosynthesis have been identified, transport mechanisms for iron, heme, or
      heme synthesis intermediates are only emerging. Recent studies have shed light on
      how these molecules are transported among various cellular compartments, as well
      as tissues. Much of this progress can be attributed to the use of model organisms
      such as S. cerevisiae, C. elegans, D. rerio, and M. musculus. Genetic studies in
      these models have led to the identification of several new genes involved in heme
      metabolism. Although our understanding has greatly improved, it is highly likely
      that other regulators exist and additional work is required to characterize the
      pathways by which heme and iron are transported within the erythron. SUMMARY: The
      identification of heme and iron transport mechanisms will improve our
      understanding of blood development and provide new insight into human blood
      disorders.

PMID- 22406825
TI  - Recent advances in vascular development.
AB  - PURPOSE OF REVIEW: This review offers a concise summary of the most recent
      experimental advances in vascular development using the mouse as a model
      organism. RECENT FINDINGS: Recent mouse studies have revealed a spread of
      phenotypic diversity between endothelia of distinct developmental origins and
      organs. For example, expression of unique transcription factors distinguishes
      hemogenic from nonhemogenic endothelium within the same vessel. Vasculature of
      the brain is particularly susceptible to endothelial malformations due to
      combinatorial germline and somatic mutations; surprisingly these mutations can
      afflict the endothelium by either cell autonomous or paracrine effects. Mutant
      mice have been used to understand how multiple signaling pathways integrate and
      refine cellular responses. In particular, we learned how VEGFR3 regulates Notch
      signaling and EphrinB2 coordinates VEGFR2 responses. The regulation of Prox1 by
      miR181 highlighted the contribution of microRNAs in the induction of lymphatic
      endothelium. Information gained on heterotypic interactions has further clarified
      the influence of blood vessels on the morphogenesis of parenchyma and contributed
      to our understanding of organ-specific endothelial differentiation. Finally,
      mouse models have uncovered endothelial cell polarity as a keystone for
      successful vascular lumenization. SUMMARY: Our understanding of the process of
      vascular development has gained significant refinement in the last two years and
      has clarified the origin of several disorders rooted in development.

PMID- 22406826
TI  - Targeted inhibition of tumor proliferation, survival, and metastasis by
      pentacyclic triterpenoids: potential role in prevention and therapy of cancer.
AB  - Over the last two decades, extensive research on plant-based medicinal compounds
      has revealed exciting and important pharmacological properties and activities of
      triterpenoids. Fruits, vegetables, cereals, pulses, herbs and medicinal plants
      are all considered to be biological sources of these triterpenoids, which have
      attracted great attention especially for their potent anti-inflammatory and anti
      cancer activities. Published reports in the past have described the molecular
      mechanism(s) underlying the various biological activities of triterpenoids which
      range from inhibition of acute and chronic inflammation, inhibition of tumor cell
      proliferation, induction of apoptosis, suppression of angiogenesis and
      metastasis. However systematic analysis of various pharmacological properties of
      these important classes of compounds has not been done. In this review, we
      describe in detail the pre-clinical chemopreventive and therapeutic properties of
      selected triterpenoids that inhibit multiple intracellular signaling molecules
      and transcription factors involved in the initiation, progression and promotion
      of various cancers. Molecular targets modulated by these triterpenoids comprise,
      cytokines, chemokines, reactive oxygen intermediates, oncogenes, inflammatory
      enzymes such as COX-2, 5-LOX and MMPs, anti-apoptotic proteins, transcription
      factors such as NF-kappaB, STAT3, AP-1, CREB, and Nrf2 (nuclear factor erythroid
      2-related factor) that regulate tumor cell proliferation, transformation,
      survival, invasion, angiogenesis, metastasis, chemoresistance and
      radioresistance. Finally, this review also analyzes the potential role of novel
      synthetic triterpenoids identified recently which mimic natural triterpenoids in
      physical and chemical properties and are moving rapidly from bench to bedside
      research.

PMID- 22406827
TI  - Targeting autophagy potentiates chemotherapy-induced apoptosis and proliferation
      inhibition in hepatocarcinoma cells.
AB  - Induction of cell death and inhibition of cell growth are the main targets of
      cancer therapy. Here we evaluated the role of autophagy on chemoresistance of
      human hepatocarcinoma (HCC) cell lines, focusing on its crosstalk with cell
      apoptosis and proliferation. In this study, a chemotherapeutic agent (cisplatin
      or 5FU) induced the formation of autophagosomes in three human HCC cell lines and
      upregulated the expression of autophagy protein LC3-II. Inhibition of autophagy
      by 3-methyladenine or si-beclin 1 increased chemotherapy-induced apoptosis in HCC
      cells. Meanwhile, increased damage of the mitochondrial membrane potential was
      also observed in HCC cells when autophagy was inhibited. Furthermore, inhibition
      of autophagy reduced clone formation and impaired cell growth of HCC cells when
      treated with chemotherapy. Co-administration of an autophagy inhibitor
      (chloroquine) and chemotherapy significantly inhibited tumor growth in a mouse
      xenograft tumor model, with greater extent of apoptosis and impaired
      proliferation of tumor cells. This study suggests that autophagy is a potential
      novel target to improve therapy efficiency of conventional chemotherapeutics
      towards HCC.

PMID- 22406829
TI  - Regulation of thrombomodulin expression in prostate cancer cells.
AB  - In carcinomas the expression of thrombomodulin (TM) is inversely correlated with
      tumour progression and metastasis. In the present study a decreased TM expression
      in human prostate cancer cell lines, LNCaP, DU-145, and PC-3, in relation to
      normal prostate epithelial cells (PrEC) is shown. Sequencing and methylation
      specific high resolution melting (MS-HRM) analyses of bisulphite-modified genomic
      DNA indicates a high degree of methylation in DU-145 cells and lesser degrees in
      PC-3 and LNCaP cells, whereas in PrEC the TM promoter is unmethylated. The
      expression of TM is negatively regulated by NF-kappaB- and GSK3-beta-dependent
      signalling pathways and positively regulated by retinoic acid and transcription
      factor Sp1 in PrEC, LNCaP and PC-3 cells, but not in DU-145 cells. However,
      exposure of DU-145 cells to the demethylating agent, 5-aza-2'deoxycytidine,
      restores the TM expression and its control by retinoic acid, NF-kappaB- and GSK3
      beta-dependent signalling. In conclusion, the study establishes that in prostate
      cancer cell lines relative to PrEC the TM is down-regulated and that the TM
      promoter is hypermethylated, which seems to be responsible for the down
      regulation and failed regulation of TM expression in DU-145 cells.

PMID- 22406828
TI  - Epigenetic biomarkers in esophageal cancer.
AB  - The aberrant DNA methylation of tumor suppressor genes is well documented in
      esophageal cancer, including adenocarcinoma (EAC) and squamous cell carcinoma
      (ESCC) as well as in Barrett's esophagus (BE), a pre-malignant condition that is
      associated with chronic acid reflux. BE is a well-recognized risk factor for the
      development of EAC, and consequently the standard of care is for individuals with
      BE to be placed in endoscopic surveillance programs aimed at detecting early
      histologic changes that associate with an increased risk of developing EAC. Yet
      because the absolute risk of EAC in individuals with BE is minimal, a clinical
      need in the management of BE is the identification of additional risk markers
      that will indicate individuals who are at a significant absolute risk of EAC so
      that they may be subjected to more intensive surveillance. The best currently
      available risk marker is the degree of dysplasia in endoscopic biopsies from the
      esophagus; however, this marker is suboptimal for a variety of reasons. To date,
      there are no molecular biomarkers that have been translated to widespread
      clinical practice. The search for biomarkers, including hypermethylated genes,
      for either the diagnosis of BE, EAC, or ESCC or for risk stratification for the
      development of EAC in those with BE is currently an area of active research. In
      this review, we summarize the status of identified candidate epigenetic
      biomarkers for BE, EAC, and ESCC. Most of these aberrantly methylated genes have
      been described in the context of early detection or diagnostic markers; others
      might prove useful for estimating prognosis or predicting response to treatment.
      Finally, special attention will be paid to some of the challenges that must be
      overcome in order to develop clinically useful esophageal cancer biomarkers.

PMID- 22406830
TI  - Selective disruption of the DNA polymerase III alpha-beta complex by the umuD
      gene products.
AB  - DNA polymerase III (DNA pol III) efficiently replicates the Escherichia coli
      genome, but it cannot bypass DNA damage. Instead, translesion synthesis (TLS) DNA
      polymerases are employed to replicate past damaged DNA; however, the exchange of
      replicative for TLS polymerases is not understood. The umuD gene products, which
      are up-regulated during the SOS response, were previously shown to bind to the
      alpha, beta and epsilon subunits of DNA pol III. Full-length UmuD inhibits DNA
      replication and prevents mutagenic TLS, while the cleaved form UmuD' facilitates
      mutagenesis. We show that alpha possesses two UmuD binding sites: at the N
      terminus (residues 1-280) and the C-terminus (residues 956-975). The C-terminal
      site favors UmuD over UmuD'. We also find that UmuD, but not UmuD', disrupts the
      alpha-beta complex. We propose that the interaction between alpha and UmuD
      contributes to the transition between replicative and TLS polymerases by removing
      alpha from the beta clamp.

PMID- 22406831
TI  - Novel insight into the non-coding repertoire through deep sequencing analysis.
AB  - Non-coding RNAs (ncRNA) account for a large portion of the transcribed genomic
      output. This diverse family of untranslated RNA molecules play a crucial role in
      cellular function. The use of 'deep sequencing' technology (also known as 'next
      generation sequencing') to infer transcript expression levels in general, and
      ncRNA specifically, is becoming increasingly common in molecular and clinical
      laboratories. We developed a software termed 'RandA' (which stands for ncRNA Read
      and-Analyze) that performs comprehensive ncRNA profiling and differential
      expression analysis on deep sequencing generated data through a graphical user
      interface running on a local personal computer. Using RandA, we reveal the
      complexity of the ncRNA repertoire in a given cell population. We further
      demonstrate the relevance of such an extensive ncRNA analysis by elucidating a
      multitude of characterizing features in pathogen infected mammalian cells. RandA
      is available for download at http://ibis.tau.ac.il/RandA.

PMID- 22406832
TI  - Genome-wide studies of the multi-zinc finger Drosophila Suppressor of Hairy-wing
      protein in the ovary.
AB  - The Drosophila Suppressor of Hairy-wing [Su(Hw)] protein is a globally expressed,
      multi-zinc finger (ZnF) DNA-binding protein. Su(Hw) forms a classic insulator
      when bound to the gypsy retrotransposon and is essential for female germline
      development. These functions are genetically separable, as exemplified by
      Su(Hw)(f) that carries a defective ZnF10, causing a loss of insulator but not
      germline function. Here, we completed the first genome-wide analysis of Su(Hw)
      binding sites (SBSs) in the ovary, showing that tissue-specific binding is not
      responsible for the restricted developmental requirements for Su(Hw). Mapping of
      ovary Su(Hw)(f) SBSs revealed that female fertility requires binding to only one
      third of the wild-type sites. We demonstrate that Su(Hw)(f) retention correlates
      with binding site affinity and partnership with Modifier of (mdg4) 67.2 protein.
      Finally, we identify clusters of co-regulated ovary genes flanked by Su(Hw)(f)
      bound sites and show that loss of Su(Hw) has limited effects on transcription of
      these genes. These data imply that the fertility function of Su(Hw) may not
      depend upon the demarcation of transcriptional domains. Our studies establish a
      framework for understanding the germline Su(Hw) function and provide insights
      into how chromatin occupancy is achieved by multi-ZnF proteins, the most common
      transcription factor class in metazoans.

PMID- 22406833
TI  - Structural, functional and evolutionary relationships between homing
      endonucleases and proteins from their host organisms.
AB  - Homing endonucleases (HEs) are highly specific DNA-cleaving enzymes that are
      encoded by invasive DNA elements (usually mobile introns or inteins) within the
      genomes of phage, bacteria, archea, protista and eukaryotic organelles. Six
      unique structural HE families, that collectively span four distinct nuclease
      catalytic motifs, have been characterized to date. Members of each family display
      structural homology and functional relationships to a wide variety of proteins
      from various organisms. The biological functions of those proteins are highly
      disparate and include non-specific DNA-degradation enzymes, restriction
      endonucleases, DNA-repair enzymes, resolvases, intron splicing factors and
      transcription factors. These relationships suggest that modern day HEs share
      common ancestors with proteins involved in genome fidelity, maintenance and gene
      expression. This review summarizes the results of structural studies of HEs and
      corresponding proteins from host organisms that have illustrated the manner in
      which these factors are related.

PMID- 22406834
TI  - Extracting regulator activity profiles by integration of de novo motifs and
      expression data: characterizing key regulators of nutrient depletion responses in
      Streptomyces coelicolor.
AB  - Determining transcriptional regulator activities is a major focus of systems
      biology, providing key insight into regulatory mechanisms and co-regulators. For
      organisms such as Escherichia coli, transcriptional regulator binding site data
      can be integrated with expression data to infer transcriptional regulator
      activities. However, for most organisms there is only sparse data on their
      transcriptional regulators, while their associated binding motifs are largely
      unknown. Here, we address the challenge of inferring activities of unknown
      regulators by generating de novo (binding) motifs and integrating with expression
      data. We identify a number of key regulators active in the metabolic switch,
      including PhoP with its associated directed repeat PHO box, candidate motifs for
      two SARPs, a CRP family regulator, an iron response regulator and that for LexA.
      Experimental validation for some of our predictions was obtained using gel-shift
      assays. Our analysis is applicable to any organism for which there is a
      reasonable amount of complementary expression data and for which motifs (either
      over represented or evolutionary conserved) can be identified in the genome.

PMID- 22406836
TI  - Bayesian estimation of bacterial community composition from 454 sequencing data.
AB  - Estimating bacterial community composition from a mixed sample in different
      applied contexts is an important task for many microbiologists. The bacterial
      community composition is commonly estimated by clustering polymerase chain
      reaction amplified 16S rRNA gene sequences. Current taxonomy-independent
      clustering methods for analyzing these sequences, such as UCLUST, ESPRIT-Tree and
      CROP, have two limitations: (i) expert knowledge is needed, i.e. a difference
      cutoff between species needs to be specified; (ii) closely related species cannot
      be separated. The first limitation imposes a burden on the user, since
      considerable effort is needed to select appropriate parameters, whereas the
      second limitation leads to an inaccurate description of the underlying bacterial
      community composition. We propose a probabilistic model-based method to estimate
      bacterial community composition which tackles these limitations. Our method
      requires very little expert knowledge, where only the possible maximum number of
      clusters needs to be specified. Also our method demonstrates its ability to
      separate closely related species in two experiments, in spite of sequencing
      errors and individual variations.

PMID- 22406835
TI  - Drosophila melanogaster linker histone dH1 is required for transposon silencing
      and to preserve genome integrity.
AB  - Histone H1 is an intrinsic component of chromatin, whose important contribution
      to chromatin structure is well-established in vitro. Little is known, however,
      about its functional roles in vivo. Here, we have addressed this question in
      Drosophila, a model system offering many advantages since it contains a single
      dH1 variant. For this purpose, RNAi was used to efficiently deplete dH1 in flies.
      Expression-profiling shows that dH1 depletion affects expression of a relatively
      small number of genes in a regional manner. Furthermore, depletion up-regulates
      inactive genes, preferentially those located in heterochromatin, while active
      euchromatic genes are down-regulated, suggesting that the contribution of dH1 to
      transcription regulation is mainly structural, organizing chromatin for proper
      gene-expression regulation. Up-regulated genes are remarkably enriched in
      transposons. In particular, R1/R2 retrotransposons, which specifically integrate
      in the rDNA locus, are strongly up-regulated. Actually, depletion increases
      expression of transposon-inserted rDNA copies, resulting in synthesis of aberrant
      rRNAs and enlarged nucleolus. Concomitantly, dH1-depleted cells accumulate extra
      chromosomal rDNA, show increased gammaH2Av content, stop proliferation and
      activate apoptosis, indicating that depletion causes genome instability and
      affects proliferation. Finally, the contributions to maintenance of genome
      integrity and cell proliferation appear conserved in human hH1s, as their
      expression rescues proliferation of dH1-depleted cells.

PMID- 22406837
TI  - Carbon and nitrogen isotopic ratios of urine and faeces as novel nutritional
      biomarkers of meat and fish intake.
AB  - PURPOSE: Meat and fish consumption are associated with changes in the risk of
      chronic diseases. Intake is mainly assessed using self-reporting, as no true
      quantitative nutritional biomarker is available. The measurement of plasma fatty
      acids, often used as an alternative, is expensive and time-consuming. As meat and
      fish differ in their stable isotope ratios, delta(13)C and delta(15)N have been
      proposed as biomarkers. However, they have never been investigated in controlled
      human dietary intervention studies. OBJECTIVE: In a short-term feeding study, we
      investigated the suitability of delta(13)C and delta(15)N in blood, urine and
      faeces as biomarkers of meat and fish intake. METHODS: The dietary intervention
      study (n = 14) followed a randomised cross-over design with three eight-day
      dietary periods (meat, fish and half-meat-half-fish). In addition, 4 participants
      completed a vegetarian control period. At the end of each period, 24-h urine,
      fasting venous blood and faeces were collected and their delta(13)C and
      delta(15)N analysed. RESULTS: There was a significant difference between diets in
      isotope ratios in faeces and urine samples, but not in blood samples (Kruskal
      Wallis test, p < 0.0001). In pairwise comparisons, delta(13)C and delta(15)N were
      significantly higher in urine and faecal samples following a fish diet when
      compared with all other diets, and significantly lower following a vegetarian
      diet. There was no significant difference in isotope ratio between meat and half
      meat-half-fish diets for blood, urine or faecal samples. CONCLUSIONS: The results
      of this study show that urinary and faecal delta(13)C and delta(15)N are suitable
      candidate biomarkers for short-term meat and fish intake.

PMID- 22406838
TI  - RWDD1 interacts with the ligand binding domain of the androgen receptor and acts
      as a coactivator of androgen-dependent transactivation.
AB  - During embryogenesis, the development of the male genital is dependent on
      androgens. Their actions are mediated by the androgen receptor (AR), which
      functions as a transcription factor. To identify AR coregulators that support AR
      action during the critical time window of androgen-dependent development in the
      genital tubercle of male mice, we performed yeast two-hybrid screenings with cDNA
      libraries of genital tubercles from male mouse embryos using human AR as bait.
      RWD domain containing 1 (RWDD1) was identified as an AR-interacting protein from
      three independent libraries of the embryonic days E15, E16 and E17. The
      interaction between the AR and RWDD1 was confirmed in vitro and in vivo and the
      ligand binding domain of the AR was shown to be sufficient to mediate the
      interaction. RWDD1 enhanced AR-dependent transactivation in reporter assays with
      promoters of different complexity and in different cell lines. These results
      suggest that RWDD1 functions as a coactivator of androgen-dependent
      transcription.

PMID- 22406839
TI  - The hinge region in androgen receptor control.
AB  - The region between the DNA-binding domain and the ligand-binding domain of
      nuclear receptors is termed the hinge region. Although this flexible linker is
      poorly conserved, diverse functions have been ascribed to it. For the androgen
      receptor (AR), the hinge region and in particular the (629)RKLKKL(634) motif,
      plays a central role in controlling AR activity, not only because it acts as the
      main part of the nuclear translocation signal, but also because it regulates the
      transactivation potential and intranuclear mobility of the receptor. It is also a
      target site for acetylation, ubiquitylation and methylation. The interplay
      between these different modifications as well as the phosphorylation at serine
      650 will be discussed here. The hinge also has an important function in AR
      binding to classical versus selective androgen response elements. In addition,
      the number of coactivators/corepressors that might act via interaction with the
      hinge region is still growing. The importance of the hinge region is further
      illustrated by the different somatic mutations described in patients with
      androgen insensitivity syndrome and prostate cancer. In conclusion, the hinge
      region serves as an integrator for signals coming from different pathways that
      provide feedback to the control of AR activity.

PMID- 22406840
TI  - Change in the electroencephalogram delta wave in the frontal cranial region of
      rats with the hyperventilation.
AB  - Hyperventilation is one way to cause activation on the electroencephalogram (EEG)
      to diagnose brain disorders. The hyperventilation is also known to affect on the
      delta power in EEG. This study divided the total delta wave into low, middle, and
      high bands corresponding to the wave frequency. The power in these three delta
      wave bands was examined in the frontal cranial region of adult male Sprague
      Dawley rats hyperventilated with ventilation (VE) of 360, 540, and 720 ml/min for
      5 min. The control group was ventilated normally with a volume of 160 ml/min. The
      results show that the relative power of the low delta band in the rats
      hyperventilated at 360 ml/min VE was significantly increased compared with powers
      of pre-hyperventilation (p<0.05). The relative power of the middle delta band was
      not significantly affected by hyperventilation at any VE, and in the high delta
      band, all of the relative powers were decreased significantly in all
      hyperventilated rats compared with powers of pre-hyperventilation (p<0.05). We
      concluded that hyperventilation affects the frontal cranial region, by increasing
      the low delta band and decreasing the high delta band.

PMID- 22406841
TI  - Consumers' willingness to pay for beef direct sales. A regional comparison across
      the Pyrenees.
AB  - Willingness to pay (WTP) for direct market of beef is investigated in two Spanish
      and two French regions located on both sides of the Pyrenees. Given the novelty
      of this distribution system, especially in Spain, a contingent valuation approach
      is undertaken, and a double-bounded model is estimated. Different patterns of
      awareness, use and WTP are found across regions. Likewise, the profile of current
      and potential users of direct sale chains is investigated. Experience in the
      different stages involved from choice to final consumption of beef, intensity of
      varied beef consumption, familiarity with direct market of food in general, and
      beef in particular, are some of the relevant factors to explain WTP and the
      probability of getting engaged into a direct distribution system of beef.

PMID- 22406842
TI  - Behaviour of metalloids and metals from highly polluted soil samples when
      mobilized by water--evaluation of static versus dynamic leaching.
AB  - The mobilization behaviour of metalloids and metals when leached by water from
      highly polluted soil/sediment samples was studied using static and dynamic
      approaches employing batch methodology and rotating coiled columns (RCC),
      respectively. Increasing the solution-to-solid ratios during batch leaching
      resulted in different enhanced mobilization rates, which are element-specific and
      matrix-specific. When dynamic leaching is employed with continuous replacement of
      the eluent, a higher portion is mobilized than when using batch elution with an
      identical solid-to-water ratio. Using RCC the time-resolved leaching of the
      elements was monitored to demonstrate the leaching patterns. For the majority of
      elements a significant decrease could be shown in the mobilized portion of the
      elements with ongoing leaching process. The data were discussed targeted at solid
      liquid partitioning coefficients of the metal(loid)s. The capabilities in
      application of K(d) values was demonstrated for dynamic leaching which is
      relevant for environmental processes.

PMID- 22406843
TI  - European-scale modelling of groundwater denitrification and associated N2O
      production.
AB  - This paper presents a spatially explicit model for simulating the fate of
      nitrogen (N) in soil and groundwater and nitrous oxide (N(2)O) production in
      groundwater with a 1 km resolution at the European scale. The results show large
      heterogeneity of nitrate outflow from groundwater to surface water and production
      of N(2)O. This heterogeneity is the result of variability in agricultural and
      hydrological systems. Large parts of Europe have no groundwater aquifers and
      short travel times from soil to surface water. In these regions no groundwater
      denitrification and N(2)O production is expected. Predicted N leaching (16% of
      the N inputs) and N(2)O emissions (0.014% of N leaching) are much less than the
      IPCC default leaching rate and combined emission factor for groundwater and
      riparian zones, respectively.

PMID- 22406844
TI  - Release of non-methane organic compounds during simulated landfilling of
      aerobically pretreated municipal solid waste.
AB  - Characteristics of non-methane organic compounds (NMOCs) emissions during the
      anaerobic decomposition of untreated (APD-0) and four aerobically pretreated (APD
      20, APD-39, APD-49, and APD-63) samples of municipal solid waste (MSW) were
      investigated in laboratory. The cumulative mass of the NMOCs of APD-20, APD-39,
      APD-49, and APD-63 accounted for 15%, 9%, 16%, and 15% of that of APD-0,
      respectively. The intensities of the NMOC emissions calculated by dividing the
      cumulative NMOC emissions by the quantities of organic matter removed (Q(VS))
      decreased from 4.1 mg/kg Q(VS) for APD-0 to 0.8-3.4 mg/kg Q(VS) for aerobically
      pretreated MSW. The lipid and starch contents might have significant impact on
      the intensity of the NMOC emissions. Alkanes dominated the NMOCs released from
      the aerobically pretreated MSW, while oxygenated compounds were the chief
      component of the NMOCs generated from untreated MSW. Aerobic pretreatment of MSW
      prior to landfilling reduces the organic content of the waste and the intensity
      of the NMOC emissions, and increases the odor threshold, thereby reducing the
      environmental impact of landfills.

PMID- 22406845
TI  - Effects of carbonation on the leachability and compressive strength of cement
      solidified and geopolymer-solidified synthetic metal wastes.
AB  - The effects of accelerated carbonation on the compressive strength and
      leachability of fly ash-based geopolymer and ordinary portland cement (OPC) doped
      with Cd(II), Cr(III), Cr(VI), Cu(II), Pb(II) or Zn(II) salts were investigated.
      Cement was effective at immobilizing Cd, Cr(III), Cu, Pb and Zn under both the
      Synthetic Precipitation Leaching Procedure (SPLP) and the Toxicity Characteristic
      Leaching Procedure (TCLP), but ineffective for retaining Cr(VI). Carbonated
      cement maintained its ability to immobilize Cd, Cr(III), Pb and Zn, but, under
      acidic TCLP conditions, was much worse at retaining Cu. Geopolymer was effective
      at immobilizing Cr(III) and Cu, and, to a lesser degree, Cd, Pb and Zn in SPLP
      leaching tests. Only Cr(III) was immobilized under comparatively acidic TCLP
      testing conditions. Carbonation did not change the metal retention capacity of
      the geopolymer matrix. Metal doping caused compressive strengths of both
      geopolymer and cement to decrease. Carbonation increased the compressive strength
      of cement, but decreased that of the geopolymer. Geochemical equilibrium modeling
      provided insight on the mechanisms of metal immobilization.

PMID- 22406846
TI  - Treatment of anaerobic digester effluents of nylon wastewater through chemical
      precipitation and a sequencing batch reactor process.
AB  - Chemical precipitation, in combination with a sequencing batch reactor (SBR)
      process, was employed to remove pollutants from anaerobic digester effluents of
      nylon wastewater. The effects of the chemicals along with various Mg:N:P ratios
      on the chemical precipitation (struvite precipitation) were investigated. When
      brucite and H(3)PO(4) were applied at an Mg:N:P molar ratio of 3:1:1, an ammonia
      removal rate of 81% was achieved, which was slightly more than that (80%)
      obtained with MgSO(4).7H(2)O and Na(2)HPO(4).12H(2)O at Mg:N:P molar ratios
      greater than the stoichiometric ratio. To further reduce the ammonia loads of the
      successive biotreatment, an overdose of phosphate with brucite and H(3)PO(4) was
      applied during chemical precipitation. The ammonia-removal rate at the Mg:N:P
      molar ratio of 3.5:1:1.05 reached 88%, with a residual PO(4)-P concentration of
      16 mg/L. The economic analysis showed that the chemical cost of chemical
      precipitation could be reduced by about 41% when brucite and H(3)PO(4) were used
      instead of MgSO(4).7H(2)O and Na(2)HPO(4).12H(2)O. The subsequent biological
      process that used a sequencing batch reactor showed high removal rates of
      contaminants. The quality of the final effluent met the requisite effluent
      discharging standards.

PMID- 22406847
TI  - Life cycle based analysis of demands and emissions for residential water-using
      appliances.
AB  - Environmental impacts of energy and water demand and greenhouse gas emissions
      from three residential water-using appliances were analyzed using life cycle
      assessment (LCA) based approach in collaboration of economic input-output model.
      This study especially focused on indirect consumption and environmental impacts
      from end-use/demand phase of each appliance. Water-related activities such as
      water supply, water heating and wastewater treatment were included in the
      analysis. The results showed that environmental impacts from end-use/demand phase
      are most significant for the water system, particularly for the energy demand for
      water heating (73% for clothes washer and 93% for showerheads). Reducing
      water/hot water consumption during the end-use/demand phase is expected to
      improve the overall water-related energy burden and water use sustainability. In
      the analysis of optimal lifespan for appliances, the estimated values (8-21
      years) using energy consumption balance approach were found to be lower than that
      using other methods (10-25 years). This implies that earlier replacement with
      efficiency models is encouraged to minimize the environmental impacts of the
      product.

PMID- 22406848
TI  - Simultaneous nitrate and organic matter removal from salmon industry wastewater:
      the effect of C/N ratio, nitrate concentration and organic load rate on batch and
      continuous process.
AB  - Although simultaneous denitrification-anaerobic digestion has been studied
      extensively, the use of salmon effluents as organic matter source has received
      little attention. This study evaluated the effect of C/N ratio, nitrate
      concentration, and organic load rate (OLR) on simultaneous nitrate and organic
      matter removal using salmon effluents. The study was carried out in a batch
      reactor with suspended biomass at 37  degrees C and pH 7.5, and in continuous
      biofilm tubular reactors at 37  degrees C fed with a mixture of a synthetic
      substrate and a saline protein-rich salmon-plant effluent. The results of the
      batch and continuous experiments showed that nitrate abatement was greater than
      95% at all the studied C/N ratios, without effect of the C/N ratio on NO(3)(-)-N
      transformation and ammonia production. An increase of nitrate concentration
      increased organic matter consumption as well as the hydrolytic rate. The organic
      matter reduction varied between 88% and 40% in the continuous process. For a
      continuous process, the increase of the OLR decreases the removal of organic
      matter.

PMID- 22406849
TI  - The impacts of prescribed moorland burning on water colour and dissolved organic
      carbon: a critical synthesis.
AB  - Discolouration of natural surface waters due to the humic component of dissolved
      organic carbon (DOC) is a costly problem for water supply companies. This paper
      reviews what is known about the impacts of prescribed moorland vegetation burning
      on water colour. Relevant research has taken place at three scales: laboratory
      experiments on peat cores, plot scale sampling of soil waters and catchment scale
      sampling of stream waters. While laboratory studies suggest burning increases
      colour production, the evidence from catchment and plot studies is contradictory.
      Plot studies suggest colour production may decrease or remain unchanged following
      burning although there is evidence for some transient changes. Catchment studies
      suggest prescribed moorland burning causes stream water colour to increase,
      although in most cases the evidence is not clear cut since most studies could not
      clearly disentangle the effects of burning from those of vegetation cover. The
      differences in findings between plot and catchment studies may be explained by:
      i) the short-term nature of some studies which do not measure long-term response
      and recovery times to burning; ii) the lack of colour measurements from shallow
      soil depths which contribute more to streamflow than soil water from deeper in
      the peat; and iii) the possibility of hydrological interactions occurring between
      different experimental plots at some sites. Additionally, the increase in recent
      patch burning in some catchments that has been statistically attributed by some
      authors to increases in stream water colour cannot be reconciled with theoretical
      calculations. When dilution with waters derived from other parts of the catchment
      are taken into account, large values of colour have to be theoretically derived
      from those recently burnt areas that occupy a small proportion of the catchment
      area in order to balance the change in stream water colour observed in recent
      years. Therefore, much further process-based work is required to properly
      investigate whether prescribed vegetation burning is a direct driver of enhanced
      colour and DOC in upland streams, rivers and lakes.

PMID- 22406850
TI  - Significant diethyl phthalate (DEP) degradation by combined advanced oxidation
      process in aqueous solution.
AB  - Ultrasound (US) combined with ultraviolet (UV) irradiation and a titanium dioxide
      (TiO(2)) catalyst was used to effectively remove diethyl phthalate (DEP) from
      aqueous solutions. Single (sonolysis, photolysis, photocatalysis) and combined
      (sonophotolysis, sonophotocatalysis) processes were performed to confirm the
      synergistic effects and DEP degradation mechanism. Using only US, the optimum
      frequency for DEP degradation was 283 kHz. At this frequency a high rate of
      hydrogen peroxide (H(2)O(2)) formation was observed of approximately 0.32 mM min(
      1). The pseudo-first order degradation rate constants were 10(-2)-10(-4) min(-1)
      depending on the process. Significant degradation and mineralization (TOC) of DEP
      were observed with the sonophotolytic and sonophotocatalytic processes. Moreover,
      synergistic effects of 1.29 and 1.95 were exhibited at the sonophotocatalytic and
      sonophotolytic DEP degradation, respectively. Furthermore, additional
      advantageous reactions may occur in the heterogeneous sonophotocatalytic process
      due to interactions between US, UV, and the photocatalyst.

PMID- 22406851
TI  - Assessment and implementation of a methodological framework for sustainable
      management: Lake Kinneret as a case study.
AB  - We outlined a methodological framework for sustainable water resource management
      comprising of ecological monitoring, quantified water quality and an ecosystem
      model. We tested the proposed framework on the subtropical Lake Kinneret
      (Israel), a major national water resource. Methodologically, this study linked
      the economic activities in Lake Kinneret and its watershed (i.e. nutrient loads
      and water supply regimes) with lake water quality, sustaining of which was
      considered as the management objective. Based on analysis of the monitoring data
      and model scenario simulations we established quantitative relationships between
      changes to lake water level and nutrient loading and water quality. We assessed a
      set of ranges of nutrient loads from the watershed and water levels that will
      allow conservation of the lake water quality within pre-defined limits thereby
      defining limits for a sustainable management policy for the lake water resources.
      The defined sustainable management policy is in good correspondence with the
      loads and water level permissible ranges estimated from the ecological monitoring
      of the lake.

PMID- 22406852
TI  - Continuous treatment of coloured industry wastewater using immobilized
      Phanerochaete chrysosporium in a rotating biological contactor reactor.
AB  - Coloured industry wastewaters often contain dyes and other toxic ingredients,
      and, therefore, pose serious threat to the receiving environment. Among the
      available methods the eco-friendly biological method has gained maximum attention
      due to its many advantages over the traditional methods. In the present study,
      continuous biological treatment of coloured wastewater from a textile dyeing
      industry was investigated using the white rot fungus Phanerochaete chrysosporium
      in a rotating biological contactor (RBC) reactor. The raw wastewater was diluted
      with an equal volume of either distilled water or media containing glucose at
      varying concentrations to study its effect on the decolourization process.
      Results revealed that the wastewater could be decolourized to an extent of more
      than 64% when diluted with media containing glucose; and, a maximum
      decolourization efficiency of 83% was obtained with 10 g/l glucose concentration.
      COD removal efficiencies were also found to be consistent with the
      decolourization efficiencies of the wastewaters. Further, the results were
      correlated with the enzyme activities of manganese peroxidase (MnP) and lignin
      peroxidase (LiP) by the fungus, which were found to play some significant role in
      decolourization of the wastewater. Results of replacing the costly carbon source
      glucose in the decolourization media with the more cheap molasses, however,
      revealed very high COD removal efficiency, but low decolourization efficiency of
      the industry wastewater.

PMID- 22406853
TI  - Design and application of surface PRBs for PCB remediation in the Canadian
      Arctic.
AB  - Over the course of three years, several surface permeable reactive barriers were
      designed and constructed to deal with leftover site contamination at a site
      located on the summit of Resolution Island, Nunavut, just southeast of Baffin
      Island at 61 degrees  35'N and 60 degrees  40'W. The site was part of a North
      American military defense system established in the 1950s that became heavily
      contaminated with polychlorinated biphenyls (PCBs) during and subsequent to, its
      operational years. Each of the three barrier designs has a different
      configuration, to meet the needs of the targeted remediation area, based on their
      unique contaminant histories. Modifications were made to the barrier designs
      based on both field observations and laboratory results. The comparison of field
      and laboratory results indicated that areas with higher concentrations of PCB
      contamination behaved differently than areas with lower concentrations of PCB
      contaminated soil. Previous laboratory studies only partially replicated field
      observations and results. It had previously been hypothesized that particle
      retention was the most important factor in trapping and capturing PCBs. However,
      rinsed filter samples from the field indicated that partitioning of PCBs between
      contaminated soil and granular activated carbon (GAC) filter particles were
      occurring at levels of 62 +/- 11%, suggesting that sequestration of the PCBs from
      the environment should be a primary focus of the barrier. This sequestration
      requires both particle retention (within the granular sorptive filters) as well
      as maintained contact time between particles for sorption processes to proceed.
      This mechanism--partitioning of PCB to GAC--was more important in areas with
      higher PCB concentration. These results suggest that it may be possible to tailor
      future barrier designs to their unique site histories and locations.

PMID- 22406854
TI  - A statistical assessment of the impact of land uses on surface water quality
      indexes.
AB  - The release of wastewater from various land uses is threatening the quality of
      surface water. Different land uses pose varying degrees of danger to water
      resources. The hazardous extent of each activity depends on the amount and
      characteristics of the wastewater. The concept of the contamination potential
      index (CPI) of an activity is introduced and applied here. The index depends on
      the quantity of wastewater from a single source and on various chemicals in the
      waste whose concentrations are above allowable standards. The CPI concept and the
      land use impact assessment are applied to the surface water conditions in Nakhon
      Nayok Province in the central region of Thailand. The land uses considered in
      this study are residential area, industrial zone, in-season and off-season rice
      farming, and swine and poultry livestock. Multiple linear regression analysis
      determines the impact of the CPIs of these land uses on certain water quality
      characteristics, i.e., total dissolved solids, electrical conductivity,
      phosphate, and chloride concentrations, using CPIs and previous water quality
      measurements. The models are further verified according to the current CPIs and
      measured concentrations. The results of the backward and forward modeling show
      that the land uses that affect water quality are off-season rice farming, raising
      poultry, and residential activity. They demonstrate that total dissolved solids
      and conductivity are reasonable parameters to apply in the land use assessment.

PMID- 22406855
TI  - Controlling gene expression with the Q repressible binary expression system in
      Caenorhabditis elegans.
AB  - We established a transcription-based binary gene expression system in
      Caenorhabditis elegans using the recently developed Q system. This system,
      derived from genes in Neurospora crassa, uses the transcriptional activator QF to
      induce the expression of target genes. Activation can be efficiently suppressed
      by the transcriptional repressor QS, and suppression can be relieved by the
      nontoxic small molecule quinic acid. We used QF, QS and quinic acid to achieve
      temporal and spatial control of transgene expression in various tissues in C.
      elegans. We also developed a split Q system, in which we separated QF into two
      parts encoding its DNA-binding and transcription-activation domains. Each domain
      showed negligible transcriptional activity when expressed alone, but expression
      of both reconstituted QF activity, providing additional combinatorial power to
      control gene expression.

PMID- 22406856
TI  - Synchronization of secretory protein traffic in populations of cells.
AB  - To dissect secretory traffic, we developed the retention using selective hooks
      (RUSH) system. RUSH is a two-state assay based on the reversible interaction of a
      hook protein fused to core streptavidin and stably anchored in the donor
      compartment with a reporter protein of interest fused to streptavidin-binding
      peptide (SBP). Biotin addition causes a synchronous release of the reporter from
      the hook. Using the RUSH system, we analyzed different transport characteristics
      of various Golgi and plasma membrane reporters at physiological temperature in
      living cells. Using dual-color simultaneous live-cell imaging of two cargos, we
      observed intra- and post-Golgi segregation of cargo traffic, consistent with
      observation in other systems. We show preliminarily that the RUSH system is
      usable for automated screening. The system should help increase the understanding
      of the mechanisms of trafficking and enable screens for molecules that perturb
      pathological protein transport.

PMID- 22406857
TI  - Single-molecule mechanical identification and sequencing.
AB  - High-throughput, low-cost DNA sequencing has emerged as one of the challenges of
      the postgenomic era. Here we present the proof of concept for a single-molecule
      platform that allows DNA identification and sequencing. In contrast to most
      present methods, our scheme is not based on the detection of the fluorescent
      nucleotides but on DNA hairpin length. By pulling on magnetic beads tethered by a
      DNA hairpin to the surface, the molecule can be unzipped. In this open state it
      can hybridize with complementary oligonucleotides, which transiently block the
      hairpin rezipping when the pulling force is reduced. By measuring from the
      surface to the bead of a blocked hairpin, one can determine the position of the
      hybrid along the molecule with nearly single-base precision. Our approach can be
      used to identify a DNA fragment of known sequence in a mix of various fragments
      and to sequence an unknown DNA fragment by hybridization or ligation.

PMID- 22406858
TI  - In silico aided metabolic engineering of Streptomyces roseosporus for daptomycin
      yield improvement.
AB  - In silico metabolic network models are valuable tools for strain improvement with
      desired properties. In this work, based on the comparisons of each pathway flux
      under two different objective functions for the reconstructed metabolic network
      of Streptomyces roseosporus, three potential targets of zwf2 (code for glucose-6
      phosphate hydrogenase), dptI (code for alpha-ketoglutarate methyltransferase),
      and dptJ (code for tryptophan oxygenase) were identified and selected for the
      genetic modifications. Overexpression of zwf2, dptI, and dptJ genes increased the
      daptomycin concentration up to 473.2, 452.5, and 489.1 mg/L, respectively.
      Furthermore, co-overexpression of three genes in series resulted in a 34.4%
      higher daptomycin concentration compared with the parental strain, which ascribed
      to the synergistic effect of the enzymes responsible for daptomycin biosynthesis.
      Finally, the engineered strain enhanced the yield of daptomycin up to 581.5 mg/L
      in the fed-batch culture, which was approximately 43.2% higher than that of the
      parental strain. These results demonstrated that the metabolic network based on
      in silico prediction would be accurate, reasonable, and practical for target gene
      identification and strain improvement.

PMID- 22406859
TI  - Improvements in ethanol production from xylose by mating recombinant xylose
      fermenting Saccharomyces cerevisiae strains.
AB  - To improve the ability of recombinant Saccharomyces cerevisiae strains to utilize
      the hemicellulose components of lignocellulosic feedstocks, the efficiency of
      xylose conversion to ethanol needs to be increased. In the present study, xylose
      fermenting, haploid, yeast cells of the opposite mating type were hybridized to
      produce a diploid strain harboring two sets of xylose-assimilating genes encoding
      xylose reductase, xylitol dehydrogenase, and xylulokinase. The hybrid strain
      MN8140XX showed a 1.3- and 1.9-fold improvement in ethanol production compared to
      its parent strains MT8-1X405 and NBRC1440X, respectively. The rate of xylose
      consumption and ethanol production was also improved by the hybridization. This
      study revealed that the resulting improvements in fermentation ability arose due
      to chromosome doubling as well as the increase in the copy number of xylose
      assimilation genes. Moreover, compared to the parent strain, the MN8140XX strain
      exhibited higher ethanol production under elevated temperatures (38  degrees C)
      and acidic conditions (pH 3.8). Thus, the simple hybridization technique
      facilitated an increase in the xylose fermentation activity.

PMID- 22406860
TI  - Photothermal effects of folate-conjugated Au nanorods on HepG2 cells.
AB  - Photothermal cancer therapy, as a prospective approach for local cancer
      treatment, is attracting increasing interests. In this paper, gold nanorods were
      conjugated with folate (folate/AuNRs), and their photothermal effects on
      hepatocellular carcinoma cell line (HepG2) using MTT assay, flow cytometry, as
      well as on the cellular morphology, cytoskeleton, cell surface adhesion, and
      stiffness detected at subcellular level by an atomic force microscope (AFM) were
      investigated. The results indicated that near-infrared laser-induced hyperthermia
      of folate/AuNRs could break the cell membrane integrity and homeostasis and then
      lead to the depolymerization of cytoskeleton and influx of intracellular Ca(2+).
      Thus, folate/AuNRs can be as effective and promising nanomaterials for
      photothermal therapy of folate receptor bearing tumor.

PMID- 22406861
TI  - Isolation of cholesterol- and deoxycholate-degrading bacteria from soil samples:
      evidence of a common pathway.
AB  - Nineteen different steroid-degrading bacteria were isolated from soil samples by
      using selective media containing either cholesterol or deoxycholate as sole
      carbon source. Strains that assimilated cholesterol (17 COL strains) were gram
      positive, belonging to the genera Gordonia, Tsukamurella, and Rhodococcus, and
      grew on media containing other steroids but were unable to use deoxycholate as
      sole carbon source. Surprisingly, some of the COL strains unable to grow using
      deoxycholate as sole carbon source were able to catabolize other bile salts
      (e.g., cholate). Conversely, strains able to grow using deoxycholate as the sole
      carbon source (two DOC isolates) were gram-negative, belonging to the genus
      Pseudomonas, and were unable to catabolize cholesterol and other sterols. COL and
      DOC were included into the corresponding taxonomic groups based on their
      morphology (cells and colonies), metabolic properties (kind of substrates that
      support bacterial growth), and genetic sequences (16S rDNA and rpoB).
      Additionally, different DOC21 Tn5 insertion mutants have been obtained. These
      mutants have been classified into two different groups: (1) those affected in the
      catabolism of bile salts but that, as wild type, can grow in other steroids and
      (2) those unable to grow in media containing any of the steroids tested. The
      identification of the insertion point of Tn5 in one of the mutants belonging to
      the second group (DOC21 Mut1) revealed that the gene knocked-out encodes an A
      ring meta-cleavage dioxygenase needed for steroid catabolism.

PMID- 22406862
TI  - Effective bioremoval and detoxification of textile dye mixture by Alishewanella
      sp. KMK6.
AB  - Alishewanella sp. strain KMK6 was able to degrade mixture of textile dyes (0.5
      2.0 g l(-1)) within 8 h. An initial 28 % reduction in COD was observed
      immediately after decolorization at static anoxic conditions which on further
      incubation at shaking conditions reduced by 90 %. Partially purified azoreductase
      was able to utilize different azo dyes as substrates. The HPLC profile of dye
      degradation showed formation of metabolic products. Further FTIR analysis showed
      significant changes in the peaks corresponding to functional groups present in
      dye mixture and its degradation products. The genotoxicity assessment showed that
      the dye degradation products were non-toxic compared to dye mixture.

PMID- 22406863
TI  - High-level expression, purification, and enzymatic characterization of truncated
      poly(vinyl alcohol) dehydrogenase in methylotrophic yeast Pichia pastoris.
AB  - A 1,965-bp fragment encoding a poly(vinyl alcohol) dehydrogenase (PVADH) from
      Sphingopyxis sp. 113P3 was synthesized based on the codon bias of the
      methylotrophic yeast Pichia pastoris. The fragment was then amplified by
      polymerase chain reaction and inserted into the site between EcoRI and NotI sites
      in pPIC9K, which was under the control of the AOX1 promoter and alpha-mating
      factor signal sequence from Saccharomyces cerevisiae. The recombinant plasmid,
      designated as pPIC9K-PVADH, was linearized using SalI and transformed into P.
      pastoris GS115 by electroporation. The PVADH activity reached 55 U/mL in a shake
      flask and 902 U/mL in a 3-L bioreactor. Surprisingly, the sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analysis and N-terminal sequencing indicated
      that the secreted PVADH was truncated, and it had only 548 amino acid residues
      (an 81-amino acid sequence from the secreted protein was cleaved). The optimum pH
      and temperature ranges for the truncated PVADH were 7.0-8.0 and 41-53  degrees C,
      respectively. The activation energy of the recombinant truncated PVADH was
      approximately 10.36 kcal/mol between 29 and 41  degrees C. Both Ca(2+) and Mg(2+)
      had stimulating effects on the activity of PVADH. With PVA1799 as the substrate,
      the truncated PVADH had a Michaelis constant (K (m)) of 1.89 mg/mL and a maximum
      reaction rate (V (max)) of 34.9 nmol/(min mg protein). To the best of our
      knowledge, this is the first report on the expression of PVADH in P. pastoris,
      and the achieved PVADH yield is the highest ever reported.

PMID- 22406864
TI  - Pseudolaric acid B-driven phosphorylation of c-Jun impairs its role in
      stabilizing HIF-1alpha: a novel function-converter model.
AB  - We have recently discovered that c-Jun executes a non-transcriptional function to
      stabilize hypoxia inducible factor 1alpha (HIF-1alpha) and that pseudolaric acid
      B (PAB) accelerates HIF-1alpha degradation and phosphorylates c-Jun at Ser63/73.
      In this study, PAB was used as a probe to investigate whether and how the
      Ser63/73 phosphorylation of c-Jun regulates its functions. The PAB-induced
      reduction of HIF-1alpha protein was rescued through supplying additional non
      phosphorylated c-Jun. However, c-Jun siRNA, which reduced both the PAB-driven
      phosphorylated c-Jun and the total c-Jun protein, did not prevent the PAB-induced
      decrease in HIF-1alpha. HIF-1alpha was revealed to be co-immunoprecipitated only
      with the non-phosphorylated c-Jun. PAB increased the phosphorylated c-Jun while
      reducing the non-phosphorylated c-Jun at Ser63/73, which impaired its function in
      stabilizing HIF-1alpha. Consequently, PAB led to the degradation of HIF-1alpha,
      thus resulting in the decreased HIF-1alpha-dependent expression of mdr-1 and
      VEGF. We accordingly propose a function-converter model of c-Jun: the Ser63/73
      phosphorylation serves as a function converter to convert c-Jun from its non
      transcriptional function to its transcriptional function.

PMID- 22406865
TI  - Will the real angiotensin converting enzyme please stand up?

PMID- 22406866
TI  - How stiffness and distal interlocking of revision hip stems influence the femoral
      cortical strain pattern.
AB  - BACKGROUND: Stress shielding and nonphysiological load transfer after primary or
      revision total hip replacement (THR) prepare the ground for resorptive bone
      remodeling. The quality of the bone stock influences the risk of periprosthetic
      fractures and the severity of future revision surgeries. The question of whether
      or not bending stiffness and distal screw interlocking influence load transfer of
      a modular revision hip stem with a solid, hollow, and hollow-slotted stem
      extension led to the conception of this experimental study. The results were
      compared with a standard hip stem for primary THR. METHODS: Revision stems were
      implanted in photoelastically coated composite femora. Cortical strain mapping
      was conducted before and after insertion of the implants under standardized
      loading conditions, considering the relevant muscle forces. Statistical analysis
      was based on a 95% confidence interval and a variance analysis for repeated
      measurements. RESULTS: Significant stress shielding was observed after insertion
      of all types of hip stems compared with the intact femora. There was also a
      marked difference between strain alterations induced by standard and revision hip
      stems. With revision stems, the most distinct stress shielding effects were
      registered with the solid stem extension, particularly in the femoral diaphysis.
      Distal interlocking screws only had a local action on strain pattern and tended
      to enhance stress shielding at the midstem area when using the more flexible
      components. CONCLUSION: More flexible revision stems provide a cortical strain
      pattern of the femur closer to the preoperative status. This may reduce
      resorptive bone remodeling in the long term. However, any type of revision stem
      tested in this study caused higher stress shielding than the hip stem for primary
      THR, especially in the diaphyseal region medially and laterally. With sufficient
      proximal anchorage, the influence of distal interlocking screws on the femoral
      strain pattern was localized.

PMID- 22406867
TI  - Midterm results of transtrochanteric anterior rotational osteotomy combined with
      shelf acetabuloplasty for osteonecrosis with acetabular dysplasia: a preliminary
      report.
AB  - BACKGROUND: Transtrochanteric anterior rotational osteotomy for osteonecrosis of
      the femoral head should be performed to obtain >34% of the ratio of transposed
      intact posterior articular surface to the acetabular weight-bearing area.
      Therefore, the presence of acetabular dysplasia is unfavorable in obtaining this
      ratio. Between 1999 and 2005, we performed the modified Spitzy shelf
      acetabuloplasty combined with anterior rotational osteotomy for three patients
      (four hips) with acetabular dysplasia. In this study, we retrospectively
      evaluated the midterm results of this combined surgery. METHODS AND RESULTS:
      Patients comprised one man and two women with a mean age of 29 years at the time
      of surgery. Mean follow-up was 7.5 years. The average preoperative Harris hip
      score of 65.5 points increased to an average of 79.3 points at the latest follow
      up. None of the hips required conversion to total hip arthroplasty during the
      follow-up periods. The average postoperative intact ratio without a shelf
      procedure was 23%, and with a shelf procedure, this ratio increased to be 58%. As
      a result, collapse progression was not observed in any of the four hips.
      CONCLUSIONS: Our results suggest that anterior rotational osteotomy combined with
      shelf acetabuloplasty may be a surgical option for osteonecrosis of the femoral
      head with acetabular dysplasia. Further studies with a larger patient population
      are necessary to clarify appropriate indications and limitations of this combined
      surgery.

PMID- 22406868
TI  - Influence of postpartum supplementation with vitamin A on the levels of
      immunoglobulin A in human colostrum.
AB  - OBJECTIVE: To evaluate the influence of supplementation with retinyl palmitate in
      the immediate postpartum period on the levels of secretory immunoglobulin A
      (SIgA) in colostrum. METHODS: A clinical trial was conducted among 96 recently
      delivered mothers treated at a public maternity hospital, divided into control
      group, which was not supplemented (n = 44), and test group, supplemented on the
      first day postpartum (n = 52). Samples of 2 mL of colostrum were collected on the
      first 2 days postpartum. SIgA was measured by turbidimetry and data were analyzed
      by the Student t test. RESULTS: Before supplementation, the average SIgA was
      829.1+/-337.6 mg/dL in the control group and 827.3+/-249.8 mg/dL in the test
      group (p = 0.52). After supplementation, the average SIgA was 343.9+/-177.2 mg/dL
      in the unsupplemented group and 501.2+/-54.5 mg/dL in the supplemented group (p <
      0.00001). CONCLUSION: The colostrum of women supplemented with retinyl palmitate
      has higher levels of SIgA, which suggests that the production of antibodies is
      modulated by vitamin A.

PMID- 22406870
TI  - A 3-dimensional spiro-functionalized platinum(II) complex to suppress
      intermolecular pi-pi and Pt...Pt supramolecular interactions for a high
      performance electrophosphorescent device.
AB  - A 3-D platinum(II)-based spirometal complex has been designed and synthesized to
      suppress aggregation and excimer emission. A prototype phosphorescent organic
      light-emitting device exhibits the high-performance orange emission with an
      external quantum efficiency of up to 5.2%.

PMID- 22406869
TI  - Evaluation of antitumour activity of tea carbohydrate polymers in hepatocellular
      carcinoma animals.
AB  - Box-Behnken design criterion was applied to identify the significant effects of
      various extraction parameters such as temperature, time, and solvent-solid ratio
      on extraction of tea carbohydrate. Among the three variables tested extraction
      temperature, and solvent-solid ratio were found to have significant effect on tea
      carbohydrate extraction. The most suitable condition for extraction of tea
      carbohydrate was found to be a single step extraction at extraction temperature
      90 degrees C, extraction time 30 min, and solvent-solid ratio 5:1. At these
      optimum extraction parameters, the maximum yield of tea carbohydrate obtained
      experimentally was found to be very close to its predicted value of 3.47% dry
      weight of root. Then, we have studied the influence of tea carbohydrate on
      biochemical parameters in hepatocellular carcinoma (HCC) animals. Hepatocellular
      carcinoma was induced by the injection of 1*10(5) H22 hepatocarcinoma cells into
      right hind thigh muscle in experimental animals. Tea carbohydrate could inhibit
      tumour growth and decrease microvessel density in tumour tissue. The altered
      amount of serum white blood cells (WBC), Interferon-gamma (IFN-gamma) and tumor
      necrosis factor-alpha (TNF-alpha) in HCC animals were dose-dependently increased,
      whereas activities of serum alanine transaminase (ALT), aspartate transaminase
      (AST) and alkaline phosphatase (ALP) were dose-dependently decreased in the drug
      treated animals. In addition, tea carbohydrate administration could decrease
      expression of vascular endothelial growth factor (VEGF) and proliferating cell
      nuclear antigen (PCNA) in H22 tumor tissue. It can be concluded that tea
      carbohydrate displayed strong antitumour activity in animals.

PMID- 22406871
TI  - Retraction. MT1-MMP cleavage of the antiangiogenic proteoglycan decorin: role in
      corneal angiogenesis: retraction.

PMID- 22406872
TI  - Dexamethasone inhibits TGF-beta2-induced migration of human lens epithelial
      cells: implications for posterior capsule opacification prevention.
AB  - The elevation of transforming growth factor-beta2 (TGF-beta2) levels in eye
      tissue is considered as one of the major factors contributing to posterior
      capsule opacification (PCO) in patients undergoing cataract surgery, since TGF
      beta2 is known to stimulate the cell migration of residual human lens epithelial
      cells (HLECs). The present study aimed to test the potential effect of
      dexamethasone (DEX) on TGF-beta2-induced cell migration and the possible cellular
      mechanisms involved in this process. Cultured HLE-B3 cells were treated with TGF
      beta2 (0.1 ng/ml) in the presence or absence of DEX (100 nM). HLE-B3 cell
      migration was determined by the Phagokinetic Track Motility Assay. Activation of
      mitogen-activated protein kinase (MAPK) signaling pathways was determined by
      Western blotting using specific phosphorylation antibodies, matrix
      metalloproteinase (MMP)-2 and MMP-9 mRNA expression, and activities were analyzed
      by RT-PCR and gelatin zymography assay, respectively. In cultured HLE-B3 cells,
      DEX largely inhibited TGF-beta2-induced cell migration and MMP activity, probably
      by inhibiting the ERK/MAPK pathway. We suggest that the use of DEX may be of help
      in the prevention of PCO formation and development.

PMID- 22406873
TI  - Evaluation of viral load in infants hospitalized with bronchiolitis caused by
      respiratory syncytial virus.
AB  - The relationship between viral load, disease severity and antiviral immune
      activation in infants suffering from respiratory syncytial virus (RSV)-associated
      bronchiolitis has not been well identified. The main objective of this study was
      to determine the existence of a correlation between RSV load and disease severity
      and also between different clinical markers and mRNA levels of the interferon
      stimulated gene (ISG)56 in infants hospitalized for bronchiolitis. We also
      evaluated whether viral load tended to be persistent over the course of the RSV
      infection. The levels of RSV-RNA were quantified in nasopharyngeal washings,
      collected from 132 infants infected with RSV as a single (90.15%) or as a dual
      infection with other respiratory viruses (9.85%). Results indicated that viral
      load was positively related to the clinical severity of bronchiolitis, the length
      of hospital stay, the levels of glycemia and the relative gene expression of
      ISG56, whereas an inverse correlation was observed with the levels of hemoglobin.
      We also found that the RSV load significantly decreased between the first and
      second nasopharingeal washings sample in most subjects. These results suggest
      that infants with high RSV load on hospital admission are more likely to have
      both more severe bronchiolitis and a higher airway activation of antiviral immune
      response.

PMID- 22406874
TI  - Phonon properties of CoSb2 single crystals.
AB  - The phonon properties of CoSb(2) have been investigated by Raman scattering
      spectroscopy and lattice dynamics calculations. Sixteen out of eighteen Raman
      active modes predicted by factor-group analysis are experimentally observed and
      assigned. The calculated and measured phonon energies at the Gamma point are in
      very good agreement. The temperature dependence of the A(g) symmetry modes is
      well represented by phonon-phonon interactions without contribution from any
      other phonon or electron related interactions.

PMID- 22406875
TI  - Effects of gender and relationship context in audio narratives on genital and
      subjective sexual response in heterosexual women and men.
AB  - Previous research suggests that heterosexual women's sexual arousal patterns are
      nonspecific; heterosexual women demonstrate genital arousal to both preferred and
      nonpreferred sexual stimuli. These patterns may, however, be related to the
      intense and impersonal nature of the audiovisual stimuli used. The current study
      investigated the gender specificity of heterosexual women's sexual arousal in
      response to less intense sexual stimuli, and also examined the role of
      relationship context on both women's and men's genital and subjective sexual
      responses. Assessments were made of 43 heterosexual women's and 9 heterosexual
      men's genital and subjective sexual arousal to audio narratives describing sexual
      or neutral encounters with female and male strangers, friends, or long-term
      relationship partners. Consistent with research employing audiovisual sexual
      stimuli, men demonstrated a category-specific pattern of genital and subjective
      arousal with respect to gender, while women showed a nonspecific pattern of
      genital arousal, yet reported a category-specific pattern of subjective arousal.
      Heterosexual women's nonspecific genital response to gender cues is not a
      function of stimulus intensity or relationship context. Relationship context did
      significantly affect women's genital sexual arousal--arousal to both female and
      male friends was significantly lower than to the stranger and long-term
      relationship contexts--but not men's. These results suggest that relationship
      context may be a more important factor in heterosexual women's physiological
      sexual response than gender cues.

PMID- 22406876
TI  - Sexual fantasies and viewing times across the menstrual cycle: a diary study.
AB  - Recent research has revealed that many aspects of female sexuality change across
      the menstrual cycle. In this study, we examined changes in sexual fantasies and
      visual sexual interests across the menstrual cycle. A total of 27 single,
      heterosexual women (M age=21.5 years) not using hormonal contraceptives answered
      questions on a web-based diary every day for 30 days about their sexual fantasies
      and behaviors. Twenty-two of them also completed a viewing time task during three
      different menstrual cycle phases (follicular, ovulation, and luteal) to assess
      changes in visual sexual interest. Ovulation status was determined by a self
      administered urine test. Results showed that the frequency and arousability of
      sexual fantasies increased significantly at ovulation. The number of males in the
      fantasies increased during the most fertile period, with no such change for the
      number of females. Fantasy content became more female-like during ovulation,
      focusing more on emotions rather than explicit sexual content. Women displayed a
      category non-specific pattern of viewing time with regard to target age and
      gender, regardless of fertility status. Results were discussed in the context of
      the ovulatory shift hypothesis of female sexuality.

PMID- 22406878
TI  - Evaluation of costs associated with tolvaptan-mediated hospital length of stay
      reduction among US patients with the syndrome of inappropriate antidiuretic
      hormone secretion, based on SALT-1 and SALT-2 trials.
AB  - BACKGROUND: Two randomized clinical trials, the Study of Ascending Levels of
      Tolvaptan in Hyponatremia 1 and 2 (SALT-1 and SALT-2), showed that tolvaptan was
      an efficacious and safe therapy for the treatment of hyponatremic patients with
      the syndrome of inappropriate antidiuretic hormone secretion (SIADH). HYPOTHESIS:
      This study evaluated the potential cost savings associated with tolvaptan usage
      based on the SALT-1 and SALT-2 trials. METHODS: Hospital length of stay (LOS)
      reduction associated with tolvaptan versus placebo was evaluated among
      hyponatremic patients with the SIADH (serum sodium < 135 mEq/L) from the combined
      data of the SALT-1 and SALT-2 trials. The Healthcare Cost and Utilization Project
      2009 Nationwide Inpatient Sample database was used to estimate hospital cost and
      LOS for hospitalizations of adult (age >= 18 years) patients with the SIADH. A
      cost-offset model was constructed to evaluate the impact of tolvaptan on hospital
      cost and LOS, with univariate and multivariate Monte Carlo sensitivity analyses.
      RESULTS: In the SALT-1 and SALT-2 trials, patients with the SIADH receiving
      tolvaptan had a shorter hospital LOS than patients receiving placebo (4.98 vs
      6.19 days, respectively). There were 21 718 hospitalizations for the SIADH
      identified from the Healthcare Cost and Utilization Project Nationwide 2009
      Inpatient Sample database, with a mean LOS of 5.7 days and mean total hospital
      costs of $8667. Using an inpatient tolvaptan treatment duration of 4 days, with a
      daily wholesale acquisition cost of $250, the cost-offset model estimated an LOS
      reduction among SIADH hospitalizations of 1.11 days. The total cost offset,
      including tolvaptan drug cost, was estimated to be $694 per admission. The cost
      neutral break-even duration of tolvaptan therapy is 6.78 days. Univariate and
      multivariate sensitivity analyses demonstrated consistent cost reduction
      associated with tolvaptan usage. Ten thousand cycles of Monte Carlo simulation
      showed the 95% CI for cost offset to be $73 to $1405. CONCLUSION: Based on the
      SALT-1 and SALT-2 trials, tolvaptan usage is associated with a shorter hospital
      LOS than placebo among patients with the SIADH. Including the drug cost for 4
      days of inpatient tolvaptan therapy, tolvaptan is associated with an estimated
      mean hospital cost reduction of $694 per admission in the United States.

PMID- 22406879
TI  - Coronary artery bypass graft surgery in acute coronary syndrome: incidence, cost
      impact, and acute clopidogrel interruption.
AB  - BACKGROUND: Guidelines stipulate that clopidogrel should be interrupted >= 5 days
      prior to elective coronary artery bypass graft (CABG) surgery to reduce the risk
      of bleeding unless the need for revascularization and/or the net benefit of the
      clopidogrel outweighs the potential risks of bleeding. This study describes real
      world patterns of acute clopidogrel use, CABG surgery, and inpatient costs among
      patients with acute coronary syndrome (ACS). METHODS: The study used the
      MarketScan(r) Commercial, Medicare Supplemental, and Hospital Drug databases,
      comprising health care data for > 63 million individuals in the United States.
      Acute coronary syndrome episodes, defined as hospitalizations for ACS (primary
      International Classification of Diseases, Ninth Revision, Clinical Modification
      codes 410.xx, 411.1x) occurring between January 1, 2005 and June 30, 2009, were
      identified from patients aged >= 18 years. Outcomes included cost of and length
      of stay (LOS) for ACS episodes and, among patients experiencing ACS episodes
      treated with acute clopidogrel administration followed by CABG surgery, the
      duration of clopidogrel interruption prior to CABG surgery. Analyses were
      descriptive. RESULTS: A total of 160 168 ACS episodes were identified, and the
      mean patient age was 63.5 years. Coronary artery bypass graft surgery episodes
      comprised 9.3% (14 896 of 160 168) of all ACS episodes. The mean LOS was 9.8
      (standard deviation [SD], 6.8) days per CABG surgery episode, and mean inpatient
      costs were $71 140 (SD, $68 012) per CABG surgery episode. Among patients
      experiencing ACS episodes with inpatient drug data and to whom acute clopidogrel
      was administered followed by CABG surgery (n = 8101), the mean duration of
      clopidogrel interruption was 3.3 (SD, 2.6) days, and the majority (62.1%) of
      these patients underwent surgery within 1 to 3 days after their last acute
      clopidogrel dose. The mean incremental increase in inpatient costs associated
      with 1 extra LOS day was $1991. CONCLUSION: Coronary artery bypass graft surgery
      is used relatively infrequently among patients who experience ACS episodes. When
      CABG surgery is performed in a real-world setting, the majority or procedures are
      performed < 5 days after the last acute clopidogrel dose. However, among patients
      for whom urgent CABG surgery is not indicated, withholding CABG surgery to allow
      for clopidogrel interruption may only minimally affect inpatient costs and must
      be considered in the broader context of patient management.

PMID- 22406877
TI  - Chromosomal defects in infertile men with poor semen quality.
AB  - PURPOSE: To assess the incidence and the type of chromosomal aberrations in males
      with infertility we reviewed cytogenetic results in 76 Tunisian infertile men (54
      nonobstructive azoospermia and 22 oligo-asthenospermia). METHODS: Karyotyping was
      performed on peripheral blood lymphocytes according to the standard methods.
      Molecular diagnosis of classical and partial Y-chromosomal microdeletions was
      performed by amplifying Y-specific STSs markers. RESULTS: Various numerical and
      structural chromosome abnormalities were identified in 15 patients (19.48%). The
      occurrence of chromosomal abnormality in the azoospermics and severe oligo
      asthnospermic was 21.7% and 13.5%, respectively. The most common was Klinefelter
      syndrome, accounting for 10 of the 15 cytogenetic defects. The total frequency of
      Y chromosomal microdeletions was 17.1%, with respective frequencies in
      azoospermic and severe oligospermic groups, 11.1% and 31.8%. The most frequent of
      Y chromosomal deletions were the partial ones (11.1% in azoospermic and 27.2% in
      oligospermic). CONCLUSION: The occurrence of chromosomal abnormalities among
      infertile males strongly suggests the need for routine genetic testing and
      counseling prior to the employment of assisted reproduction techniques.

PMID- 22406880
TI  - Cost-effectiveness analysis of varenicline versus existing smoking cessation
      strategies in Central America and the Caribbean using the BENESCO model.
AB  - OBJECTIVES: In Central American countries, the economic burden of tobacco has not
      been assessed. In Costa Rica, a study demonstrated that tobacco-related diseases
      represent high costs for the health care system. The aim of this study was to
      assess the cost-effectiveness of varenicline compared with other existing
      strategies for smoking cessation within a 10-year time horizon in an adult
      population cohort from Central American and Caribbean countries using the health
      care payer's perspective. METHODS: The Benefits of Smoking Cessation on Outcomes
      simulation model was used for an adult cohort in Costa Rica (n = 2 474 029),
      Panama (n = 2 249 676), Nicaragua (n = 3 639 948), El Salvador (n = 4 537 803),
      and the Dominican Republic (n = 6 528 125) (N = 19 429 581). Smoking cessation
      therapies compared were varenicline (0.5-2 mg/day) versus bupropion (300 mg/day),
      nicotine replacement therapy (5-15 mg/day), and unaided cessation. Effectiveness
      measures were: life-years (LYs) gained and quality-adjusted life-years (QALYs)
      gained. Resource use and cost data were obtained from a country's Ministry of
      Health and/or Social Security Institutions (2008-2010). The model used a 5%
      discount rate for costs (expressed in 2010 US$) and health outcomes.
      Probabilistic sensitivity analyses were conducted and acceptability curves were
      constructed. RESULTS: Varenicline reduced smoking-related morbidity, mortality,
      and health care costs in each country included in the study. Accumulatively,
      mortality in the varenicline arm was reduced by 1190, 1538, and 2902 smoking
      related deaths compared with bupropion, nicotine replacement therapy, and unaided
      cessation, respectively. The net average cost per additional quitter showed that
      varenicline was cost-saving when compared with competing alternatives. Regarding
      LYs and QALYs gained in 10 years, varenicline obtained the greatest number of
      QALYs and LYs in each country, while unaided cessation obtained the fewest. Cost
      effectiveness analyses in all 5 countries showed that varenicline was the
      dominant strategy. Acceptability curves showed that, independent of the
      willingness to pay, the probability that varenicline is cost-effective was 99%
      for this region. The results of the probabilistic sensitivity analyses support
      the robustness of the findings. CONCLUSION: Smoking cessation therapy with
      varenicline is cost-saving for the Central American and Caribbean countries
      included. These results could help to reduce the tobacco-related disease burden
      and align cost-containment policies.

PMID- 22406881
TI  - Cost analysis of varenicline versus bupropion, nicotine replacement therapy, and
      unaided cessation in Nicaragua.
AB  - OBJECTIVES: In Nicaragua, 30% of current morbidities are associated with tobacco
      smoking. Tobacco control policy measures have been initiated in this Central
      American country; however, the population does not have a complete understanding
      of the long-term consequences of tobacco use. The aim of this study was to
      compare the direct medical costs of smoking cessation therapies with varenicline,
      bupropion, nicotine replacement therapy, and unaided cessation in Nicaragua over
      5 time horizons: 2, 5, 10, and 20 years, and lifetime. METHODS: The current
      annual costs of chronic obstructive pulmonary disease, lung cancer, coronary
      heart disease, and stroke were estimated based on the current annual incidence
      for each disease using 1 public hospital database (Hospital Lenin Fonseca, 2010).
      The Benefits of Smoking Cessation on Outcomes simulation model was used to obtain
      the projected direct costs for each strategy. An adult cohort (N = 3 639 948)
      from Nicaragua was used and the assessment was conducted using the health care
      payer's perspective. Costs were discounted at 5% annually. Probabilistic
      sensitivity analyses were conducted using a Monte Carlo second-order approach.
      RESULTS: Varenicline is associated with the highest health care cost-savings
      compared with the other 3 alternatives at 5, 10, and 20 years, and lifetime. At
      lifetime, varenicline would result in savings of US$4 545 008, US$5 859 300, and
      US$11 033 221 when compared with bupropion, nicotine replacement therapy, and
      unaided cessation, respectively. Varenicline also avoided the highest number of
      smoking-related deaths in comparison with the alternatives. At year 10,
      varenicline avoided 96, 124, and 234 more deaths than bupropion, nicotine
      replacement therapy, and unaided cessation, respectively. The results of
      probabilistic sensitivity analyses support these findings. CONCLUSION: The use of
      a smoking cessation therapy with varenicline would generate long-term savings to
      Nicaragua's health care institutions of > US$11 million in the lifetime time
      horizon.

PMID- 22406882
TI  - Antimicrobial prophylaxis in noncardiac prosthetic device recipients.
AB  - BACKGROUND: Secondary antimicrobial prophylaxis involves the use of >= 1
      antimicrobial agent just prior to the time when a diagnostic/therapeutic
      procedure, which may induce infection, is to be performed. In the context of this
      article, antimicrobial agent(s) are administered to patients with >= 1 implanted
      prosthetic device in order to prevent metastatic seeding of the device(s) during
      bacteremia induced by a diagnostic/therapeutic procedure. Antimicrobial agents
      used in this context are only administered periprocedurally. Secondary
      antimicrobial prophylaxis of endocarditis in recipients of cardiac prosthetic
      materials (including valves, shunts, conduits, and patches) has been reasonably
      well established. However, secondary antimicrobial prophylaxis in recipients of
      other types of prosthetic devices has been the subject of much controversy, with
      a wide variety of recommendations being made. OBJECTIVES: The purpose of this
      article was to conduct a narrative review of the published literature on the
      topic of secondary antimicrobial prophylaxis in recipients of noncardiac
      prosthetic devices and make evidence-based recommendations for each type of
      device, where possible. METHODS: Medline/PubMed and EMBASE databases were
      searched for English-language articles published from 1950 to the present
      (January 2012). Search terms included "prophylaxis," "antibiotics,"
      "antimicrobials," "prosthetic devices," "prosthesis-related infections,"
      "bacteremia," the names of the individual types of prosthetic devices, and the
      names of the individual procedures potentially inducing bacteremia. Articles
      dealing with any aspect relevant to this topic were eligible for review. The
      bibliographies of retrieved articles were also carefully scanned to identify any
      articles not previously identified. RESULTS: Based on review of the available
      literature, secondary antimicrobial prophylaxis is justified in only a few
      specific circumstances. For recipients of prosthetic vascular grafts/stents,
      hemodialysis arteriovenous shunts, and ventriculoatrial/ventriculovenous shunts,
      prophylaxis is warranted during the initial 6 months, initial 6 weeks, and at all
      times after implantation/revision, respectively, when dental procedures capable
      of inducing high-level bacteremia are planned. Prosthetic joint recipients should
      receive prophylaxis in the following 3 circumstances: 1) patient is to undergo
      dental procedure(s) capable of inducing high-level bacteremia plus either the
      patient is still within 2 years of device implantation/revision or the patient
      has >= 1 risk factor for hematogenous prosthetic joint infection; 2) patient is
      to undergo genitourinary tract procedure(s) capable of inducing high-level
      bacteremia plus the patient has >= 1 risk factor for high-risk bacteriuria; and
      3) patient is to undergo perforating dermatologic surgery on the oral mucosa or
      at skin sites at increased risk for surgical site infection plus patient has >= 1
      risk factor for hematogenous prosthetic joint infection. The data are inadequate
      to justify secondary antimicrobial prophylaxis for recipients of other types of
      prosthetic devices. On the basis of 9 surveys of prescriber behavior, it is
      apparent that there exists, over a wide geographic area, a wide disconnect
      between clinical practice and the secondary antimicrobial prophylaxis guidelines
      issued by the professional organizations representing these prescribers.
      Antimicrobial agent overuse was especially problematic among orthopedic and
      colorectal surgeons, urologists, and family practitioners. Dentists and
      maxillofacial surgeons followed guidelines more closely. CONCLUSION: Device-,
      procedure-, and patient characteristic-dependent factors elicited over many years
      have narrowed down the secondary antimicrobial prophylaxis recommendations for
      noncardiac prosthetic devices to a small number. Despite this, physician
      prescribers frequently do not follow prophylaxis guidelines established by their
      own professional organizations. Risk-benefit and cost-effectiveness studies have
      found that no prophylaxis is actually superior to universal prophylaxis, likely
      due to known antimicrobial toxicities, such as anaphylactic/anaphylactoid
      reactions and Clostridium difficile-associated disease. Much work remains in
      establishing and extending the scientific basis for secondary antimicrobial
      prophylaxis and transforming this knowledge into appropriate action by the
      clinician.

PMID- 22406883
TI  - Outpatient antibiotic prescribing in a low-risk veteran population with acute
      respiratory symptoms.
AB  - BACKGROUND: Acute respiratory tract infections are usually caused by viruses and
      are self-limited in healthy adults. Providers frequently provide antibiotic
      prescriptions for sinusitis, bronchitis, pharyngitis, and nonspecific upper
      respiratory tract infections, despite no evidence of improved clinical outcomes.
      We sought to determine: 1) primary care providers' antibiotic prescribing
      practices for acute respiratory tract infections in low-risk outpatient veterans
      and 2) short-term health outcome differences between those receiving and not
      receiving an antibiotic prescription. METHODS: We performed a retrospective
      electronic medical record review for veterans presenting to 1 of 3 primary care
      outpatient Veterans Affairs clinics in Portland, OR between July 1, 2008 and June
      30, 2009 for acute respiratory symptoms. Demographics, signs and symptoms,
      antibiotic prescriptions, nonantibiotic prescriptions, and laboratory and imaging
      study variables were abstracted from medical charts. Descriptive frequencies,
      bivariate analyses (t tests, rank sums, Chi square tests, and Fisher's exact
      tests), and multivariate analyses (logistic regression) were performed. RESULTS:
      35.4% of patients received antibiotic prescriptions. Of those antibiotics, 87.8%
      were not indicated. Antibiotic regimen prescriptions varied widely for each
      diagnosis. Short-term outcomes of hospitalization, follow-up visits, later
      antibiotic prescriptions, and death at 30 days were not associated with receipt
      of antibiotics. CONCLUSION: Many low-risk veterans received antibiotics for acute
      respiratory tract infections despite guidelines indicating that symptomatic
      treatment is sufficient for most patients. Novel interventions are required to
      reduce unnecessary and potentially harmful antibiotic use for low-risk
      outpatients with acute respiratory complaints.

PMID- 22406884
TI  - Strategies for prevention of ventilator-associated pneumonia: bundles, devices,
      and medications for improved patient outcomes.
AB  - Ventilator-associated pneumonia is associated with significant patient morbidity,
      mortality, and increased health care costs. In the current economic climate, it
      is crucial to implement cost-effective prevention strategies that have proven
      efficacy. Multiple prevention measures have been proposed by various expert
      panels. Global strategies have focused on infection control, and reduction of
      lower airway colonization with bacterial pathogens, intubation, duration of
      mechanical ventilation, and length of stay in the intensive care unit. Routine
      use of the Institute for Healthcare Improvement ventilator care bundle is
      widespread, and has been clearly demonstrated to be an effective method for
      reducing the incidence of ventilator-associated pneumonia. In this article, we
      examine specific aspects of the Institute for Healthcare Improvement bundle,
      better-designed endotracheal tubes, use of antibiotics and probiotics, and
      treatment of ventilator-associated tracheobronchitis to prevent ventilator
      associated pneumonia.

PMID- 22406885
TI  - Ventilator-associated pneumonia: a review.
AB  - Ventilator-associated pneumonia (VAP) is the most common infection seen in
      intensive care units (ICUs); it accounts for one-fourth of the infections
      occurring in critically ill patients and is the reason for half of antibiotic
      prescriptions in mechanically ventilated patients. In addition to being a
      financial burden on ICUs, it continues to contribute significantly to the
      morbidity and mortality of ICU patients, with an estimated attributable mortality
      rate of 8% to 15%. While the pathophysiology of VAP remains relatively unchanged,
      diagnostic techniques and preventive measures are constantly evolving. The focus
      of this article is on recent trends in VAP epidemiology, modifiable risk factors,
      diagnostic techniques, challenges in management, and current data on the
      prevention of VAP. Important messages that the reader should take away include:
      1) There is no gold standard for the diagnosis of VAP; whenever VAP is suspected,
      if feasible, a quantitative culture should be obtained by invasive or noninvasive
      methods (whichever is more readily available before initiation of antibiotics);
      2) Suspicion based on clinical features should prompt the initiation of a broad
      spectrum of antibiotics depending on suspected pathogens; 3) Close attention
      should be paid to de-escalation of antibiotics once microbiological results
      become available or as the patient starts responding clinically; the ideal
      duration of treatment should be 8 days instead of the conventional 10 to 14 days,
      except in situations where Pseudomonas may be suspected or the patient's
      comorbidities dictate otherwise; and 4) Prevention remains the key to reducing
      the burden of VAP. We promote the proven preventive measures of using noninvasive
      ventilation when possible, semirecumbent patient positioning, continuous
      aspiration of subglottic secretions, and oral chlorhexidine washes along with
      stress ulcer prophylaxis only after careful assessment of the risks versus
      benefits.

PMID- 22406886
TI  - Prevention and management of central line-associated bloodstream infections in
      hospital practice.
AB  - In this article aimed at hospitalists, we examine the literature on preventive
      measures for central line-associated bloodstream infections (CLABSIs) and optimal
      management once a CLABSI has been established. We focus on a number of core
      preventive measures and the contemporary approach of bundling these measures for
      maximal impact in reducing infection rates. We then discuss empiric and pathogen
      specific antibiotic therapy, including the role of newer antimicrobial agents, as
      well as the management of an infected central venous catheter.

PMID- 22406887
TI  - An overview of the diagnosis and management of Clostridium difficile infection.
AB  - The diagnosis and treatment of Clostridium difficile infection are becoming
      increasingly complex with the introduction of novel diagnostic techniques and new
      pharmacologic and nonpharmacologic treatments. The integration of these new
      approaches with older, established methods is a challenge to individual
      clinicians and hospital systems. This article provides an overview of the current
      methods for the diagnosis and treatment of C difficile infection.

PMID- 22406888
TI  - Nosocomial diarrhea: a review of pathophysiology, etiology, and treatment
      strategies.
AB  - Diarrhea is a frequent complication among hospitalized patients. Nosocomial
      diarrhea is generally diagnosed as increased frequency and decreased consistency
      of stools developing after 72 hours of hospitalization. The causes of nosocomial
      diarrhea may be infectious or noninfectious. Noninfectious etiologies occur most
      commonly, and are often adverse effects of medications or enteral nutrition
      therapies. Infectious etiologies are most concerning and include Clostridium
      difficile and norovirus. Patients with nosocomial diarrhea should be placed in
      isolation with contact precautions in place until the presence of C difficile
      infection is determined. Irrespective of etiology, diarrhea can cause serious
      complications in hospitalized patients, including malnutrition, hemodynamic
      instability, metabolic acidosis, and potentially fatal pseudomembranous colitis.
      This article reviews nosocomial diarrhea, including its pathophysiology,
      infectious and noninfectious causes, and treatment strategies based on identified
      cause.

PMID- 22406889
TI  - Clostridium difficile colitis: a review.
AB  - Clostridium difficile has become an increasingly important nosocomial pathogen
      and is one of the most common causes of hospital-acquired diarrhea. The incidence
      of C difficile infection (CDI) is increasing worldwide. Overuse of antibiotics is
      felt to be a major contributing factor leading to the increased incidence of CDI.
      The clinical manifestations of CDI vary from a mild form of the disease to
      fulminant diarrhea, leading to significant patient morbidity and mortality. The
      increasing incidence of CDI has a major impact on increasing health care costs.
      This article will summarize the epidemiology, pathogenesis, clinical
      manifestations, laboratory diagnosis, and treatment options for CDI, as well as
      infection-control measures for the prevention of CDI.

PMID- 22406890
TI  - A review of opioids for in-hospital pain management.
AB  - In the postoperative pain setting, the use of opioid analgesics remains essential
      in achieving effective analgesia and in avoiding the deleterious sequelae of
      uncontrolled pain that can worsen patient outcomes. However, postoperative pain
      remains undertreated in many patients. Choosing the most appropriate use of
      opioids in the postoperative setting, especially for patients undergoing ongoing
      opioid treatment for chronic pain, can pose daunting challenges for many
      clinicians. In this article, we examine the pitfalls that may be encountered when
      implementing postoperative pain management strategies with opioid analgesics,
      especially in patients receiving chronic opioid therapy prior to admission, and
      the critical steps for appropriate and effective analgesia in this setting.

PMID- 22406891
TI  - Evaluating therapeutic benefit in postsurgical analgesia requires global
      assessment: an example from liposome bupivacaine in hemorrhoidectomy.
AB  - BACKGROUND AND OBJECTIVE: Interpreting analgesic efficacy based solely on
      measures of pain intensity can be misleading. Here, we use data from an adult
      hemorrhoidectomy study to demonstrate the importance of evaluating pain intensity
      scores with other outcome measures in interpreting analgesic study results.
      METHODOLOGY: We looked for coordinated outcome measures including pain intensity
      at rest using a numeric rating scale (NRS), postsurgical consumption of rescue
      medication, subject-reported results from the Brief Pain Inventory, subject
      satisfaction with postsurgical analgesia, and adverse events. RESULTS: The
      analgesic efficacy of liposome bupivacaine was reflected in a significant
      reduction in pain intensity scores at each timed assessment during the first 12
      to 24 hours after surgery (mean NRS at 12 hours: liposome bupivacaine, 2.2;
      placebo, 2.9; P = 0.04), and less consumption of opioid rescue medications
      thereafter through 72 hours postsurgery (mean total amount of opioids consumed:
      liposome bupivacaine, 10 mg; placebo, 18 mg; P = 0.0006). These observations are
      supported by results of other outcome measures, including time to first use of
      opioid rescue medication, pain-related interference of subject functionality, and
      subject satisfaction with postsurgical analgesia. CONCLUSION: Liposome
      bupivacaine produced superior analgesia when compared with placebo at early
      postoperative time points, but appropriate use of rescue medication diminished
      this effect after 12 hours. However, based on our assessment of multiple outcome
      measures used in the study, it appears that the therapeutic benefit associated
      with the tested analgesic lasted throughout the 72-hour study period.

PMID- 22406892
TI  - An update in options for the treatment of pain: a review of new opioid
      formulations.
AB  - In the past 2 decades, there has been a significant increase in the use of
      opioids for the management of chronic nonmalignant pain. This increase in usage
      has led to concerns of misuse and abuse of opioids. Also, many of the available
      opioid options were previously only available as oral tablets or capsules,
      further limiting treatment options for health care providers. Several new opioid
      formulations have been developed to address and prevent the misuse and abuse of
      opioids via tampering in the United States. In addition, alternative delivery
      systems have been developed to provide physicians with more options to provide
      adequate pain management for those with chronic pain. This article reviews new
      opioid options for the treatment of pain management and requirements of the Risk
      Evaluation and Mitigation Strategies program.

PMID- 22406893
TI  - Transition of patients with COPD across different care settings: challenges and
      opportunities for hospitalists.
AB  - Hospitalists play an important role in treating current and preventing future
      acute exacerbations of chronic obstructive pulmonary disease (AECOPD), which are
      associated with high rates of medical resource use and morbidity. Comprehensive
      admission screening and diagnostic tests are important in enabling hospitalists
      to reliably identify patients with AECOPD, the severity of the episode, and
      related issues that may prolong patients' hospital length of stay. Recurring
      exacerbations, especially those that require repeated acute care, can reduce
      physical activity and accelerate pulmonary decline and risk of death. Recommended
      pharmacotherapies for AECOPD should include short-acting bronchodilators,
      systemic corticosteroids, and appropriate antibiotics in cases of suspected
      bacterial infection. Patients with demonstrable hypoxemia or respiratory failure
      may benefit from oxygen and/or ventilatory support. Long-term disease management
      with the goal of preventing future exacerbations should include ongoing emphasis
      toward smoking cessation and up-to-date vaccination, in addition to prescribing
      maintenance pharmacotherapies in accordance with respiratory treatment
      guidelines. Additional benefits may be derived from nonpharmacologic therapies,
      such as pulmonary rehabilitation, weight-loss recommendations, and treatment of
      obstructive sleep dyspnea when present. Effective communication among members of
      the inpatient and outpatient health care teams, the patient, and his or her
      caregivers is an important aspect of care transitions. Hospital discharge
      summaries should be transmitted to the patient's primary care physician and be
      readily available at the first follow-up visit. Discharge coaches and other
      allied health care providers can aid hospitalists in reinforcing self-management
      skills and patient education, and in emphasizing the importance of follow-up
      visits. Recent findings suggest that health and cost benefits are associated with
      improved COPD management. This article focuses on the pivotal role of the
      hospitalist in promoting and facilitating the steps toward improving quality
      outcomes and transitions of care for patients with COPD.

PMID- 22406894
TI  - Occurrence and predictors of dexmedetomidine infusion intolerance and failure.
AB  - BACKGROUND: Dexmedetomidine, a selective alpha2 adrenergic receptor agonist,
      exhibits sedative, analgesic, anxiolytic, and sympatholytic effects, and may aid
      in controlling agitation in the intensive care unit (ICU). At our hospital
      (Barnes-Jewish Hospital, St. Louis, MO), dexmedetomidine is commonly used as a
      sedative in the medical ICU. Predictors of dexmedetomidine intolerance or failure
      have not yet been defined. OBJECTIVE: Describe the rate of dexmedetomidine
      infusion intolerance/failure and identify patient predictors of
      intolerance/failure. METHODS: This retrospective single-center cohort study
      evaluated 75 mechanically ventilated adults who received dexmedetomidine
      infusion. Patients were included in the study if they were aged >= 18 years;
      mechanically ventilated for > 24 hours; received dexmedetomidine infusion for >=
      1 hour following > 24 hours of continuous infusions of midazolam, fentanyl, or
      propofol; and were admitted to our medical ICU between August 1, 2009 and August
      1, 2010. Multivariate logistic regression analysis was performed to identify
      independent predictors of intolerance/failure. RESULTS: A total of 85 episodes of
      dexmedetomidine infusion were analyzed (75 total patients). Eighteen episodes
      (21%) met the criteria for intolerance/failure and 67 episodes (79%) met the
      criteria for tolerance/success. The median duration of mechanical ventilation,
      total dexmedetomidine infusion time, and ICU length of stay did not differ
      between groups. Nonblack race was the only variable independently associated with
      treatment failure or intolerance in the logistic regression analysis. CONCLUSION:
      Twenty-one percent of dexmedetomidine infusion episodes met the criteria for
      intolerance/failure. No predictors of intolerance/failure were found to be
      clinically significant.

PMID- 22406895
TI  - Routinely assessed biochemical markers tested on admission as predictors of
      adverse outcomes in hospitalized elderly patients.
AB  - AIM: To explore whether routinely assessed biochemical markers tested on
      admission will predict 3 predefined adverse outcomes for hospitalized elderly
      patients: discharge to a long-term care facility, in-hospital mortality, and
      prolonged hospital length of stay (> 14 days). METHODS: A prospective
      observational study of elderly patients (aged >= 75 years) admitted to an acute
      care geriatric ward over a 6-month period. Patients were assessed on admission
      and baseline characteristics were collected. Activities of daily living were
      assessed by the Barthel Index and cognitive function by the abbreviated mental
      test. Results from biochemical markers tested on admission were downloaded from
      the pathology laboratory database using patient details. Patients were followed
      up with until discharge or in-hospital mortality. RESULTS: A total of 392
      patients formed the study population. Mean (standard deviation) age was 83.2 (+/-
      5.5) years and 283 (72%) patients were men. Thirty-eight (10%) patients were
      discharged to a long-term care facility, 134 (34%) had a prolonged hospital
      length of stay, and 33 (8%) died in the hospital. Results from testing 5
      biochemical markers independently predicted in-hospital mortality:
      hypoalbuminemia (adjusted odds ratio [OR], 2.5; 95% CI, 0.9-6.7; P = 0.04), low
      total cholesterol level (adjusted OR, 2.9; 95% CI, 1.3-6.3; P = 0.01),
      hyperglycemia (adjusted OR, 2.9; 95% CI, 1.2-7.4; P = 0.02), high C-reactive
      protein level (adjusted OR, 4.2; 95% CI, 1.3-13.4; P = 0.01), and renal
      impairment (adjusted OR, 3.8; 95% CI, 1.7-8.7; P = 0.002). High C-reactive
      protein level independently predicted prolonged hospital length of stay (OR, 1.7;
      95% CI, 1.1-2.9; P = 0.03). Hypoalbuminemia predicted discharge to a long-term
      care facility independent of confounding factors except for physical dysfunction
      (OR, 2.4; 95% CI, 1.1-5.1; P = 0.03). Significance was reduced after adjustment
      for Barthel Index score (OR, 1.9; 95% CI, 0.9-4.1; P = 0.08). CONCLUSION: Testing
      of routinely assessed biochemical markers on admission predicted adverse hospital
      outcomes for elderly patients. Their inclusion in a standardized prediction tool
      may help to create interventions to improve such outcomes.

PMID- 22406896
TI  - Posterior reversible encephalopathy syndrome: clinicoradiological spectrum and
      therapeutic strategies.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome of
      encephalopathy, headache, visual disturbance, and seizures. In most cases,
      symptoms present acutely or subacutely in the setting of accelerated
      hypertension, eclampsia, autoimmune disease, immunosuppressive treatment, or
      cancer chemotherapy. One essential feature of PRES is the presence of reversible
      cerebral vasogenic edema that has a predominantly posterior distribution on brain
      imaging. Atypical imaging features are commonly described, including involvement
      of the anterior brain or brainstem and the coexistence of ischemia or hemorrhage.
      In most cases, both clinical and radiological findings are reversible, although
      permanent imaging abnormalities and residual neurological sequelae can be seen in
      a minority of patients. The syndrome is thought to be caused by a breakdown of
      the blood-brain barrier and an extravasation of the intravascular fluid.
      Treatment of hypertension and seizures, and withdrawal of causative agents are
      the mainstays of therapy in PRES.

PMID- 22406897
TI  - Can postoperative cognitive dysfunction be avoided?
AB  - Postoperative cognitive dysfunction (POCD) refers to a postoperative decline in
      cognitive function compared with preoperative cognitive function. Diagnosis
      requires pre- and postoperative testing, the latter of which is usually performed
      both 7 days and 3 months postoperatively. Although several risk factors for POCD
      have been described, age is the only consistently reported risk factor.
      Postoperative cognitive dysfunction is often transient. It may last several
      months, and is associated with leaving the labor market prematurely and increased
      mortality. As the pathophysiology of POCD is still a matter of debate and is
      likely to be multifactorial, there are no widely accepted prophylactic and
      therapeutic interventions. In this article, we discuss POCD's definition, risk
      factors, long-term significance, and pathophysiology. We also present data on
      prophylactic interventions that have been investigated in clinical trials.

PMID- 22406898
TI  - Contemporary management of ST-segment elevation myocardial infarction.
AB  - Coronary heart disease is the leading cause of death worldwide. In the United
      States, approximately 1 of every 6 deaths in 2007 was caused by coronary heart
      disease. Clinical presentation in the acute setting is mostly due to
      atherosclerotic plaque rupture leading to flow limitation in the affected vessel,
      and myocardial ischemia and infarction. ST-segment elevation myocardial
      infarction is usually associated with complete occlusion of the coronary artery
      and carries the worst prognosis in terms of in-hospital mortality. Despite
      various advances in treatment options, including percutaneous coronary
      intervention, ischemic heart disease still carries a significant morbidity and
      mortality. In this article, we aim to provide a summary of a few key advances in
      the management of ST-segment elevation myocardial infarction.

PMID- 22406899
TI  - An update on coronary artery chronic total occlusions.
AB  - A coronary artery chronic total occlusion (CTO) represents a coronary artery that
      has been occluded for a long period of time, typically months. Coronary artery
      CTOs are common and occur in approximately one-third of patients referred for
      coronary angiography. Revascularization of CTO is technically challenging and has
      historically been associated with lower procedural success rates and higher
      complication rates. Technical success of CTO revascularization has significantly
      improved given remarkable advances in interventional cardiology over the past 3
      decades. However, the decision to perform CTO revascularization remains a
      dilemma, given the lack of robust clinical evidence to support its use.

PMID- 22406900
TI  - Evaluation of traditional Chinese medicinal plants for anti-MRSA activity with
      reference to the treatment record of infectious diseases.
AB  - The in vitro antimicrobial activities of 30 Chinese medicinal plants were
      evaluated with reference to the treatment record of infectious diseases in the
      Traditional Chinese Medicine (TCM) literature. The plant materials were extracted
      with 80% ethanol and the extracts were primarily screened against conventional
      clinical pathogens like Staphylococcus aureus, Escherichia coli, Pseudomonas
      aeruginosa and Candida albicans by the agar diffusion method. Their inhibition
      zone diameters (IZDs, mm, 50 mg/mL) ranged from 2,048 by the standard broth
      microdilution method. The seven extracts from M. yunnanensis, S. sinensis, G.
      morella, E. daneillii, M. squamulata, S. arborescens and B. hancei were
      determined as the most active extracts, with MICs of 8-64 MUg/mL. The results
      were in good agreement with their traditional applications in skin and other
      infections.

PMID- 22406901
TI  - Isolation of glycinin (11S) from lipid-reduced soybean flour: effect of
      processing conditions on yields and purity.
AB  - Defatted soybean flour was treated with hexane and ethanol to reduce lipid
      content and heated to inactivate lipoxygenase (LOX, linoleate:oxygen reductase;
      EC 1.13.11.12) to obtain lipid-reduced soybean flour (LRSF). The effects of
      processing conditions such as pH, reducing agent and storage time on yields and
      purity of glycinin (11S) were evaluated in the fractionation of soybean glycinin
      isolated from LRSF. Adjusting the pH of protein extract from 6.2 to 6.6, the
      yield of glycinin decreased by 16.71%, while the purity of the protein increased
      by 4.60%. Sulfhydryl and disulfide content of proteins increased by degrees with
      increasing pH. Compared with dithiothreitol (DTT) or beta-mercaptoethanol (ME) as
      reducing agent, the yield of glycinin was the highest when sodium bisulfite (SBS)
      was added to the protein extract at pH 6.4. The effect of DTT on yields of
      glycinin was the lowest of the three kinds of reducing agent. The purity of
      glycinin was similar when the three kinds of reducing agent were used. These
      results showed that SBS was the best choice for the isolation of 11S-rich
      fraction. Prolonging storage time in the precipitation stage, 10 h was the best
      for yields and purity of glycinin in the experiment, while there was no
      significant difference at P >= 0.05 for total sulfhydryl and disulfide content.
      The decreased free sulfhydryl content of glycinin indicated that the oxidation of
      free sulfhydryls and the formation of disulfide bonds occurred when the
      extraction time was prolonged.

PMID- 22406902
TI  - Isolation and characterization of an antibacterial peptide fraction from the
      pepsin hydrolysate of half-fin anchovy (Setipinna taty).
AB  - Enzymatic proteolysis of food proteins is considered a promising method to
      generate antibacterial peptides. The objective of the present study was to
      isolate and characterize peptide fraction from the pepsin hydrolysate of half-fin
      anchovy (Setipinna taty) with antibacterial activity against Escherichia coli.
      The most active peptide fraction HAHp2-3-I was isolated by a series of
      chromatographic methods, including Sephadex G-25 chromatography, reverse high
      performance liquid chromatography (RP-HPLC) and Source 5RPC ST. Peptides
      identification of HAHp2-3-I was carried out using UPLC-LTQ-Orbitrap mass
      spectrometer. HAHp2-3-I contained five cationic peptides (MLTTPPHAKYVLQW,
      SHAATKAPPKNGNY, PTAGVANALQHA, QLGTHSAQPVPF and VNVDERWRKL) and three anionic
      peptides (LATVSVGAVELCY, NPEFLASGDHLDNLQ and PEVVYECLHW). Prediction of peptide
      secondary structure indicated that these anionic peptides should have extended
      strand and random coil structures, whereas cationic peptides PTAGVANALQHA and
      VNVDERWRKL could form alpha helixes. In addition, results of scanning electron
      microscopy (SEM) revealed that treatment by HAHp2-3-I could cause the
      morphological changes of E. coli and destruction of the cell integrity via
      irreversible membrane damage. The results could provide information for
      investigating the antibacterial model of antibacterial peptides derived from fish
      protein hydrolysates.

PMID- 22406903
TI  - Effect of electrospun non-woven mats of dibutyryl chitin/poly(lactic acid) blends
      on wound healing in hairless mice.
AB  - The aim of this study was to examine the proliferative ability of dibutyryl
      chitin (DBC) on scratch wounds in HaCaT keratinocytes and to evaluate the effect
      of nanoporous non-woven mat (DBCNFM) on skin wound healing in hairless mice using
      the advantages of DBCNFM, such as high porosity and high surface area to volume.
      The cell spreading activity of DBC was verified through a cell spreading assay in
      scratched human HaCaT keratinocytes. Scratch wound experiments showed that DBC
      notably accelerates the spreading rate of HaCaT keratinocytes in a dose dependent
      manner. The molecular aspects of the healing process were also investigated by
      hematoxylin & eosin staining of the healed skin, displaying the degrees of
      reepithelialization and immunostaining on extracellular matrix synthesis and
      remodeling of the skin. Topical application of DBCNFM significantly reduced skin
      wound rank scores and increased the skin remodeling of the wounded hairless mice
      in a dose dependent way. Furthermore, DBCNFM notably increased the expression of
      the type 1 collagen and filaggrin. These results demonstrate that DBC efficiently
      accelerates the proliferation of HaCaT keratinocytes and DBCNFM notably increases
      extracellular matrix synthesis on remodeling of the skin, and these materials are
      a good candidate for further evaluation as an effective wound healing agent.

PMID- 22406904
TI  - Recovery and concentration of antioxidants from winery wastes.
AB  - Grape and wine byproducts have been extensively studied for the recovery of
      phenolic compounds with antioxidant activity and a variety of biological actions.
      The selective recovery and concentration of the phenolic compounds from the
      liquid phase separated from further diluted winery wastes has been proposed.
      Adsorption onto non ionic polymeric resins and further desorption with ethanolic
      solutions was studied. Several commercial food grade resins were screened with
      the aim of selecting the most suited for the practical recovery of phenolic
      compounds with radical scavenging activity. Under the optimized desorption
      conditions (using Sepabeads SP207 or Diaion HP20 as adsorbents and eluting with
      96% ethanol at 50  degrees C) a powdered yellow-light brown product with 50%
      phenolic content, expressed as gallic acid equivalents, was obtained. The radical
      scavenging capacity of one gram of product was equivalent to 2-3 g of Trolox.

PMID- 22406905
TI  - 1H and 13C-NMR data of the simplest plumeran indole alkaloids isolated from
      Aspidosperma species.
AB  - Indole alkaloids are the chemotaxonomic markers of the Aspidosperma genera. Those
      that have the simplest plumeran skeleton are classified as the precursors of
      biosynthetic routes and the intermediates for several synthetic reactions. This
      work aims to review the 1H and 13C-NMR data, up to 2011, describing the skeleton
      of 35 different plumeran indole alkaloids, from a group of 46 of them, and
      highlight the main spectral differences amongst them.

PMID- 22406906
TI  - Metabolic syndrome and quality of life in the elderly: age and gender
      differences.
AB  - PURPOSE: The metabolic syndrome (MetS) is highly prevalent in Western older
      populations. MetS is an intriguing entity, because it includes potentially
      reversible risk factors. Some studies have suggested an inverse correlation
      between MetS and health-related quality of life (HRQoL), but data regarding older
      subjects are scanty and conflicting. The aim of this study was to assess the
      association between HRQoL and MetS in older, unselected community-dwelling
      subjects. METHODS: We analyzed data of 356 subjects aged 75+ living in Tuscania
      (Italy). HRQoL was assessed using the Health Utilities Index, Mark 3. Diagnosis
      of MetS was defined according to the National Cholesterol Education Program's ATP
      III criteria. RESULTS: MetS was reported by 137 (38%) participants. According to
      linear regression analysis, MetS was associated with significantly better HRQoL
      in men (B = 0.19 95% CI = 0.06-0.32; p = 0.006), but not in women. Also, when the
      regression model was analyzed in men, MetS was associated with better HRQoL (B =
      0.17, 95% CI = 0.01-0.32; p = 0.035) only among participants aged 80+. No
      significant associations were found in men between HRQoL and any of the single
      components of MetS. CONCLUSIONS: MetS is not associated with worse HRQoL among
      community-dwelling elderly; it is associated with significantly better HRQoL
      among the oldest men.

PMID- 22406907
TI  - Comparison of the effects of weight loss from a high-protein versus standard
      protein energy-restricted diet on strength and aerobic capacity in overweight and
      obese men.
AB  - PURPOSE: To compare the effects of two low-fat, hypoenergetic diets differing in
      carbohydrate-to-protein ratio, on strength and aerobic capacity measures in
      overweight and obese men. METHODS: In a parallel design, 56 men (age, 45.5 +/-
      8.7 years; BMI, 33.6 +/- 3.9 kg/m(2)) were randomly assigned to a low-fat, energy
      restricted diet (7,000 kJ/day) with either high protein (HP:
      protein/carbohydrate/fat % energy, 35:40:25) or standard protein (SP, 17:58:25).
      Body weight, body composition, muscle strength and aerobic capacity were assessed
      at baseline and after 12 weeks. RESULTS: Forty-two participants completed the
      study (HP, n = 21; SP, n = 21). Both groups experienced similar reductions in
      body weight (HP, -10.7 +/- 5.3 kg [-9.8%]; SP, -8.7 +/- 3.5 kg [-8.4%]) and fat
      free mass (HP, -2.8 +/- 3.6 kg; SP, -3.2 +/- 2.7 kg; P < 0.001 time; P > 0.14
      time * group interaction). There was a trend for a greater reduction in fat mass
      in the HP diet group, (-7.7 +/- 4.3 kg [-21.2%] vs. -5.4 +/- 3.3 kg [-15.1%]; P <
      0.001 time; P = 0.06 time * group interaction). Absolute peak oxygen uptake did
      not change in either group (P = 0.39 time; P = 0.50 time * group interaction).
      Overall, in both groups, relative peak oxygen uptake increased (2.9 +/- 2.8 ml
      kg(-1) min(-1) [8.9%]), peak isometric knee extensor strength increased (14.1 +/-
      35.7 Nm [7.1%]) and peak handgrip strength decreased (-1.6 +/- 4.1 kg [-3%]) (P
      <= 0.02 time for all), with no diet effect (P <= 0.23 time * group interaction).
      CONCLUSION: In overweight and obese men, both a HP and SP diet reduced body
      weight and improved body composition with similar effects on strength and aerobic
      capacity.

PMID- 22406908
TI  - In vivo biostability of polyurethane-organosilicate nanocomposites.
AB  - Organically modified layered silicates were incorporated into a polyether soft
      segment polyurethane to form composites of at least delaminated morphology. The
      primary organic modifier was a quaternary ammonium compound; however, one
      composite included an alternative amino undecanoic acid-modified silicate. The
      composites' biostability was assessed in an in vivo ovine model over a period of
      6 weeks. Attenuated total reflectance-Fourier transform infrared analysis and
      semi-quantitative scanning electron microscopy image rating indicate a
      significant enhancement of the base polyurethane biostability with the inclusion
      of silicate at 3 wt.%. The potential effect at 15 wt.% was confounded by probable
      leaching of the quaternary ammonium compound affecting the tissue response. The
      amino undecanoic acid composite compared favourably with the quaternary ammonium
      compound composite of equivalent silicate loading, and offers the promise of a
      more favourable tissue response.

PMID- 22406909
TI  - A novel approach for blood purification: mixed-matrix membranes combining
      diffusion and adsorption in one step.
AB  - Hemodialysis is a commonly used blood purification technique in patients
      requiring kidney replacement therapy. Sorbents could increase uremic retention
      solute removal efficiency but, because of poor biocompatibility, their use is
      often limited to the treatment of patients with acute poisoning. This paper
      proposes a novel membrane concept for combining diffusion and adsorption of
      uremic retention solutes in one step: the so-called mixed-matrix membrane (MMM).
      In this concept, adsorptive particles are incorporated in a macro-porous membrane
      layer whereas an extra particle-free membrane layer is introduced on the blood
      contacting side of the membrane to improve hemocompatibility and prevent particle
      release. These dual-layer mixed-matrix membranes have high clean-water permeance
      and high creatinine adsorption from creatinine model solutions. In human plasma,
      the removal of creatinine and of the protein-bound solute para-aminohippuric acid
      (PAH) by single and dual-layer membranes is in agreement with the removal
      achieved by the activated carbon particles alone, showing that under these
      experimental conditions the accessibility of the particles in the MMM is
      excellent. This study proves that the combination of diffusion and adsorption in
      a single step is possible and paves the way for the development of more efficient
      blood purification devices, excellently combining the advantages of both
      techniques.

PMID- 22406910
TI  - Ca-Mg-Zn bulk metallic glasses as bioresorbable metals.
AB  - A series of six unique Ca-based bulk metallic glasses were synthesized and
      characterized. The glasses were designed to consist solely of the biocompatible
      elements Ca, Mg and Zn, with the view to their potential use as bioresorbable
      metals for orthopaedic applications. The alloys had a critical casting thickness
      of up to 4.5 mm. Mechanical and thermophysical testing revealed a Young's modulus
      (stiffness) of ~40 GPa. Glass transition temperatures ranged from 119 to 129
      degrees C, above which the alloys can be formed like a thermoplastic polymer. In
      vitro biocorrosion testing using a combination of polarization and mass loss
      techniques revealed that the corrosion rate of these alloys is relatively rapid,
      although, in some cases, it may be tailored through alloy composition.

PMID- 22406911
TI  - Sodium dodecyl sulfate-induced rapid gelation of silk fibroin.
AB  - The in situ formation of injectable silk fibroin (SF) hydrogels have potential
      advantages over various other biomaterials due to the minimal invasiveness during
      application. Biomaterials need to gel rapidly under physiological conditions
      after injection. In the current paper, a novel way to accelerate SF gelation
      using an anionic surfactant, sodium dodecyl sulfate (SDS), as a gelling agent is
      reported. The mechanism of SDS-induced rapid gelation was determined. At low
      surfactant concentrations, hydrophobic interactions among the SF chains played a
      dominant role in the association, leading to decreased gelation time. At higher
      concentrations of surfactant, electrostatic repulsive forces among micellar
      aggregates gradually became dominant and gelation was hindered. Gel formation
      involves the connection of clusters formed by the accumulation of nanoparticles.
      This process is accompanied by the rapid formation of beta-sheet structures due
      to hydrophobic and electrostatic interactions. It is expected that the silk
      hydrogel with short gelation time will be used as an injectable hydrogel in drug
      delivery or cartilage tissue engineering.

PMID- 22406912
TI  - Amphiphilic block co-polymers: preparation and application in nanodrug and gene
      delivery.
AB  - Self-assembly of amphiphilic block co-polymers composed of poly(ethylene oxide)
      (PEO) as the hydrophilic block and poly(ether)s, poly(amino acid)s, poly(ester)s
      and polypropyleneoxide (PPO) as the hydrophobic block can lead to the formation
      of nanoscopic structures of different morphologies. These structures have been
      the subject of extensive research in the past decade as artificial mimics of
      lipoproteins and viral vectors for drug and gene delivery. The aim of this review
      is to provide an overview of the synthesis of commonly used amphiphilic block co
      polymers. It will also briefly go over some pharmaceutical applications of
      amphiphilic block co-polymers as "nanodelivery systems" for small molecules and
      gene therapeutics.

PMID- 22406913
TI  - Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized
      controlled trials.
AB  - Assessments of lysergic acid diethylamide (LSD) in the treatment of alcoholism
      have not been based on quantitative meta-analysis. Hence, we performed a meta
      analysis of randomized controlled trials in order to evaluate the clinical
      efficacy of LSD in the treatment of alcoholism. Two reviewers independently
      extracted the data, pooling the effects using odds ratios (ORs) by a generic
      inverse variance, random effects model. We identified six eligible trials,
      including 536 participants. There was evidence for a beneficial effect of LSD on
      alcohol misuse (OR, 1.96; 95% CI, 1.36-2.84; p = 0.0003). Between-trial
      heterogeneity for the treatment effects was negligible (I2 = 0%). Secondary
      outcomes, risk of bias and limitations are discussed. A single dose of LSD, in
      the context of various alcoholism treatment programs, is associated with a
      decrease in alcohol misuse.

PMID- 22406914
TI  - Collateral flow measurement by phase-contrast magnetic resonance imaging for the
      assessment of systemic venous baffle patency after atrial switch repair for
      transposition of the great arteries.
AB  - PURPOSE: We aimed to describe and compare azygos vein flow patterns of patients
      with obstructed and unobstructed systemic venous baffle after atrial switch
      repair for d-transposition of the great arteries (TGA). We hypothesized that
      phase-contrast magnetic resonance imaging would enable characterization of
      retrograde collateral flow across the azygos vein in cases of systemic venous
      baffle obstruction. MATERIALS AND METHODS: This is a retrospective, cross
      sectional study. Twelve patients with atrial switch repair for TGA were examined.
      Azygos flow index was measured with phase-contrast magnetic resonance imaging;
      comparison was made between patients with documented systemic venous baffle
      obstruction (n=3) and a control group of patients without baffle obstruction
      (n=9). RESULTS: Patients with systemic venous baffle obstruction had a
      distinctive azygos flow pattern that was retrograde and an increased amount of
      azygos flow compared with patients without obstruction [median (range), -436 (
      455/-399) vs. 103 (51/125) mL/min/m2; P=0.01]. CONCLUSIONS: Patients with
      systemic venous baffle obstruction have a characteristic collateral flow across
      the azygos vein. Azygos vein flow measurement may be used for the assessment of
      baffle patency in patients after atrial switch repair for TGA. However,
      diagnostic accuracy needs to be tested in a larger population.

PMID- 22406916
TI  - [Flat panel technology in the orthopaedic trauma operating room].
AB  - The advantages of flat panel detector technology with X-ray sensitive
      semiconductor technology has increasingly gained acceptance in the inpatient
      setting for diagnostic X-ray imaging in recent years and has replaced
      conventional X-ray films. For intraoperative imaging C-arms, not least for cost
      reasons, are still based on conventional image intensifier technology. By
      improving the robustness of the flat panel technology and cost-effective
      production, future spread of these technologies in the OR could be expected.
      Direct digital imaging with improved image quality, with a possible reduction in
      radiation dose while at the same time enlarging the image field, can affect the
      procedural quality of surgery. A return on investment can be achieved in part by
      saving time and avoiding additional postoperative imaging.

PMID- 22406917
TI  - [Intraoperative augmented reality visualization. Current state of development and
      initial experiences with the CamC].
AB  - The intraoperative application of augmented reality (AR) has so far mainly taken
      place in the field of endoscopy. Here, the camera image of the endoscope was
      augmented by computer graphics derived mostly from preoperative imaging. Due to
      the complex setup and operation of the devices, they have not yet become part of
      routine clinical practice. The Camera Augmented Mobile C-arm (CamC) that extends
      a classic C-arm by a video camera and mirror construction is characterized by its
      uncomplicated handling. It combines its video live stream geometrically correct
      with the acquired X-ray. The clinical application of the device in 43 cases
      showed the strengths of the device in positioning for X-ray acquisition, incision
      placement, K-wire placement, and instrument guidance. With its new function and
      the easy integration into the OR workflow of any procedure that requires X-ray
      imaging, the CamC has the potential to become the first widely used AR technology
      for orthopedic and trauma surgery.

PMID- 22406919
TI  - Correlation of non-mass-like abnormal MR signal intensity with pathological
      findings surrounding pediatric osteosarcoma and Ewing's sarcoma.
AB  - OBJECTIVE: The aim of this work was to determine the role of MRI in interpreting
      abnormal signals within bones and soft tissues adjacent to tumor bulk of
      osteosarcoma and Ewing's sarcoma in a pediatric population by correlating MR
      findings with histopathology. MATERIALS AND METHODS: Thirty patients met the
      inclusion criteria, which included (1) osteosarcoma or Ewing's sarcoma, (2) MR
      studies no more than 2 months prior to surgery, (3) presence of abnormal MR
      signal surrounding the tumor bulk, (4) pathological material from resected tumor.
      The patients received standard neoadjuvant chemotherapy. Using grid maps on gross
      pathology specimens, the abnormal MR areas around the tumor were matched with the
      corresponding grid sections. Histopathology slides of these sections were then
      analyzed to determine the nature of the regions of interest. The MR/pathological
      correlation was evaluated using Mann-Whitney U test and Fisher's exact test.
      RESULTS: Twenty-seven patients had osteosarcoma and three patients had Ewing's
      sarcoma. Of the studied areas, 17.4% were positive for tumor (viable or
      necrotic). There was no statistically significant correlation between areas
      positive for tumor and age, gender, signal extent and intensity on MRI, or tissue
      type. There was, however, a statistically significant correlation between
      presence of tumor and the appearance of abnormal soft tissue signals. A feathery
      appearance correlated with tumor-negative areas whereas a bulky appearance
      correlated with tumor-positive regions. CONCLUSIONS: MR imaging is helpful in
      identifying the nature of abnormal signal areas surrounding bone sarcomas that
      are more likely to be tumor-free, particularly when the signal in the soft
      tissues surrounding the tumor is feathery and edema-like in appearance.

PMID- 22406918
TI  - [Emergency anesthesia, airway management and ventilation in major trauma.
      Background and key messages of the interdisciplinary S3 guidelines for major
      trauma patients].
AB  - Patients with multiple trauma presenting with apnea or a gasping breathing
      pattern (respiratory rate  < 6/min) require prehospital endotracheal intubation
      (ETI) and ventilation. Additional indications are hypoxia (S(p)O(2)  < 90%
      despite oxygen insufflation and after exclusion of tension pneumothorax), severe
      traumatic brain injury [Glasgow Coma Scale (GCS)  < 9], trauma-associated
      hemodynamic instability [systolic blood pressure (SBP)  < 90 mmHg] and severe
      chest trauma with respiratory insufficiency (respiratory rate  > 29/min). The
      induction of anesthesia after preoxygenation is conducted as rapid sequence
      induction (analgesic, hypnotic drug, neuromuscular blocking agent). With the
      availability of ketamine as a viable alternative, the use of etomidate is not
      encouraged due to its side effects on adrenal function. An electrocardiogram
      (ECG), blood pressure measurement and pulse oximetry are needed to monitor the
      emergency anesthesia and the secured airway. Capnography is absolutely mandatory
      to confirm correct placement of the endotracheal tube and to monitor tube
      dislocations as well as ventilation in the prehospital and hospital setting.
      Because airway management is often complicated in trauma patients, alternative
      devices need to be available preclinical and a fiber-optic endoscope should be
      available within the hospital. Use of these alternative measures for airway
      management and ventilation should be considered at the latest after a maximum of
      three unsuccessful endotracheal intubation attempts. Emergency medical service
      (EMS) physicians should to be trained in emergency anesthesia, ETI and
      alternative methods of airway management on a regular basis. Within hospitals
      ETI, emergency anesthesia and ventilation are to be conducted by trained and
      experienced anesthesiologists. When a difficult airway or induction of anesthesia
      is expected, endotracheal intubation should be supervised or conducted by an
      anesthesiologist. Normoventilation should be the goal of mechanical ventilation.
      After arrival in the resuscitation room the ventilation will be controlled and
      guided with the help of arterial blood gas analyses. After temporary removal of a
      cervical collar, the cervical spine needs to be immobilized by means of manual in
      line stabilization when securing the airway.

PMID- 22406920
TI  - Psychological treatments for concurrent posttraumatic stress disorder and
      substance use disorder: a systematic review.
AB  - This article gives an overview of research into psychological treatments for
      concurrent posttraumatic stress disorder (PTSD) and substance used disorder
      (SUD), with a special focus on the effectiveness of treatments addressing both
      disorders compared to treatments addressing one of the disorders alone. In
      addition, a distinction is made between trauma-focused versus non-trauma-focused
      therapies for concurrent PTSD and SUD. The databases Embase, Psychinfo, Medline
      and Web of science were searched for relevant articles. In total, seventeen
      studies were identified evaluating ten treatments protocols (six trauma-focused
      and four non-trauma-focused treatment approaches). In general, the studies showed
      pre-post reductions for PTSD and/or SUD symptoms. Although most treatments for
      concurrent PTSD and SUD did not prove to be superior to regular SUD treatments,
      there are some promising preliminary results suggesting that some patients might
      benefit from trauma-focused interventions. However, the lack of methodologically
      sound treatment trials makes it difficult to draw firm conclusions.
      Methodological limitations are discussed, along with recommendations for future
      research.

PMID- 22406921
TI  - Stochastic sensing of proteins with receptor-modified solid-state nanopores.
AB  - Solid-state nanopores are capable of the label-free analysis of single molecules.
      It is possible to add biochemical selectivity by anchoring a molecular receptor
      inside the nanopore, but it is difficult to maintain single-molecule sensitivity
      in these modified nanopores. Here, we show that metallized silicon nitride
      nanopores chemically modified with nitrilotriacetic acid receptors can be used
      for the stochastic sensing of proteins. The reversible binding and unbinding of
      the proteins to the receptors is observed in real time, and the interaction
      parameters are statistically analysed from single-molecule binding events. To
      demonstrate the versatile nature of this approach, we detect His-tagged proteins
      and discriminate between the subclasses of rodent IgG antibodies.

PMID- 22406923
TI  - n-3 polyunsaturated fatty acids inhibit lipopolysaccharide-induced microglial
      activation and dopaminergic injury in rats.
AB  - Increasing evidence indicates that neuroinflammation plays an important role in
      neurotoxins-induced neurodegenerations. Microglia are a type of glial cells in
      the brain and play as the first and main form of active immune defense in the
      central nervous system. Accumulated data suggest that the activation of microglia
      plays a critical role in neurotoxicities induced by environmental toxicants. So
      the inhibition of microglia has been proven to be an effective strategy against
      neurotoxic effects. In the present study, we found that n-3 polyunsaturated fatty
      acids can inhibit both microglial activation and dopaminergic injury in the
      substantia nigra of Sprague-Dawley rats induced by lipopolysaccharide, one of the
      major constituents of the outer membrane of Gram-negative bacteria. Moreover, n-3
      polyunsaturated fatty acids inhibited lipopolysaccharide-induced activation of
      nuclear factor-kappaB, an important transcription factor involved in microglial
      activation. Taken together, our results provided the first in vivo evidence that
      n-3 polyunsaturated fatty acids can inhibit the damage of dopaminergic neurons
      induced by lipopolysaccharide through their inhibitory effects on nuclear factor
      kappaB-dependent microglial activation.

PMID- 22406922
TI  - Interactions between endothelial progenitor cells (EPC) and titanium implant
      surfaces.
AB  - OBJECTIVES: Endothelial cells play an important role in peri-implant angiogenesis
      during early bone formation. Therefore, interactions between endothelial
      progenitor cells (EPCs) and titanium dental implant surfaces are of crucial
      interest. The aim of our in vitro study was to investigate the reactions of EPCs
      in contact with different commercially available implant surfaces. MATERIALS AND
      METHODS: EPCs from buffy coats were isolated by Ficoll density gradient
      separation. After cell differentiation, EPC were cultured for a period of 7 days
      on different titanium surfaces. The test surfaces varied in roughness and
      hydrophilicity: acid-etched (A), sand-blasted-blasted and acid-etched (SLA),
      hydrophilic A (modA), and hydrophilic SLA (modSLA). Plastic and fibronectin
      coated plastic surfaces served as controls. Cell numbers and morphology were
      analyzed by confocal laser scanning microscopy. Secretion of vascular endothelial
      growth factor (VEGF)-A was measured by enzyme-linked immunosorbent assay and
      expressions of iNOS and eNOS were investigated by real-time polymerase chain
      reaction. RESULTS: Cell numbers were higher in the control groups compared to the
      cells of titanium surfaces. Initially, hydrophilic titanium surfaces (modA and
      modSLA) showed lower cell numbers than hydrophobic surfaces (A and SLA). After 7
      days smoother surfaces (A and modA) showed increased cell numbers compared to
      rougher surfaces (SLA and modSLA). Cell morphology of A, modA, and control
      surfaces was characterized by a multitude of pseudopodia and planar cell soma
      architecture. SLA and modSLA promoted small and plump cell soma with little
      quantity of pseudopodia. The lowest VEGF level was measured on A, the highest on
      modSLA. The highest eNOS and iNOS expressions were found on modA surfaces.
      CONCLUSIONS: The results of this study demonstrate that biological behaviors of
      EPCs can be influenced by different surfaces. The modSLA surface promotes an
      undifferentiated phenotype of EPCs that has the ability to secrete growth factors
      in great quantities. CLINICAL RELEVANCE: In correlation with recent clinical
      studies these results underline the hypothesis that EPC could promote and
      increase neovascularization by secreting paracrine factors which support
      osseointegration of dental implants.

PMID- 22406924
TI  - Peginesatide and erythropoietin stimulate similar erythropoietin receptor
      mediated signal transduction and gene induction events.
AB  - Peginesatide is a synthetic, PEGylated, peptide-based erythropoiesis-stimulating
      agent that is designed and engineered to stimulate specifically the
      erythropoietin receptor dimer that governs erythropoiesis. Peginesatide has a
      unique structure that consists of a synthetic peptide dimer (with no sequence
      similarity to erythropoietin) conjugated to a 40-kDa PEG moiety. Peginesatide is
      being developed for the treatment of anemia associated with chronic kidney
      disease in dialysis patients. To compare signaling effects of peginesatide to
      recombinant human erythropoietin (rHuEPO), dose-dependent effects on protein
      phosphorylation and gene expression were evaluated using phosphoproteomics,
      quantitative signal transduction analyses, and gene profiling. After stimulation
      with peginesatide or rHuEPO, cell lysates were prepared from UT-7/EPO cells.
      Liquid chromatography-tandem mass spectrometry and MesoScale arrays were used to
      quantify phosphorylation events. Transcriptional changes were analyzed using
      microarrays and quantitative reverse transcription polymerase chain reaction.
      Peginesatide and rHuEPO were found to regulate the tyrosine phosphorylation of an
      essentially equivalent set of protein substrates, and modulate the expression of
      a similar set of target genes. Consistent with their roles in stimulating
      erythropoiesis, peginesatide and rHuEPO regulate similar cellular pathways.

PMID- 22406925
TI  - Soluble factors secreted by glioblastoma cell lines facilitate recruitment,
      survival, and expansion of regulatory T cells: implications for immunotherapy.
AB  - In patients with glioma, the tumor microenvironment can significantly impact pro
      inflammatory immune cell functions. However, the mechanisms by which this occurs
      are poorly defined. Because immunosuppressive regulatory T cells (Treg) are over
      represented in the tumor microenvironment compared with peripheral blood, we
      hypothesized that the tumor may have an effect on Treg survival, migration,
      expansion, and/or induction of a regulatory phenotype from non-Treg conventional
      CD4+ T cells. We defined the impact of soluble factors produced by tumor cells on
      Treg from healthy patients in vitro to determine mechanisms by which gliomas
      influence T cell populations. We found that tumor-derived soluble factors allowed
      for preferential proliferation and increased chemotaxis of Treg, compared with
      conventional T cells, indicating that these mechanisms may contribute to the
      increased Treg in the tumor microenvironment. Conventional T cells also exhibited
      a significantly increased expression of pro-apoptotic transcripts in the presence
      of tumor-derived factors, indicating that survival of Treg in the tumor site is
      driven by exposure to soluble factors produced by the tumor. Together, these data
      suggest that tumor burden may induce increased Treg infiltration, proliferation,
      and survival, negating productive anti-tumor immune responses in patients treated
      with immunotherapies. Collectively, our data indicate that several mechanisms of
      Treg recruitment and retention in the tumor microenvironment exist and may need
      to be addressed to improve the specificity of immunotherapies seeking to
      eliminate Treg in patients with glioma.

PMID- 22406926
TI  - Impaired survival and long-term neurological problems in benign meningioma.
AB  - PURPOSE: To assess long-term functional outcome and survival among patients with
      meningioma World Health Organization (WHO) grade I. METHODS: Retrospective
      analysis of 205 patients after resection of WHO grade I intracranial meningioma
      from 1985 through 2003. Expected age- and sex-specific survival was calculated by
      applying Dutch life-table statistics to each patient for the individual duration
      of follow-up. Long-term functional outcome was assessed using a mailed
      questionnaire to the general practitioner. RESULTS: The mean duration of follow
      up was 11.5 years. Survival at 5, 10, 15, and 20 years was 92%, 81%, 63%, and
      53%, respectively, which is significantly lower than the expected survival (94%,
      86%, 78%, and 66%, respectively). Survival was worse with higher age (P < .001).
      Survival among patients younger than 45 years and older than 65 years was
      comparable to the expected survival but significantly worse among patients aged
      45-65 years. Analysis of the cause of death suggests an excess mortality
      associated with both brain tumor death and stroke (P = .07). Recurrence rates at
      5, 10, and 15 years were 18%, 26%, and 32%, respectively. Higher Simpson grade (P
      < .001) and lower age (P = .02) were associated with a higher recurrence rate. In
      29 patients (14%) receiving radiotherapy, the 5-year recurrence rate was 18% and
      the 5-year survival was only 58%. Long-term functioning (>= 5 years after last
      treatment) could be assessed in 89 long-term survivors: 29 patients (33%) showed
      no deficits, and 60 (67%) showed at least 1 neurological symptom, of whom 24
      (27%) were unable to perform normal daily activities. CONCLUSION: Long-term
      survival in WHO grade I meningioma is challenged in patients more than 45 years
      of age. Excess mortality seems to be associated with both tumor recurrence and
      stroke. The majority of patients have long-term neurological problems.

PMID- 22406927
TI  - N-Heterocyclic carbenes via abstraction of ammonia: 'normal' carbenes with
      'abnormal' character.
AB  - A new ammonia adduct of a N-heterocyclic carbene (NHC) has been isolated, which
      can be used as a reagent for the synthesis of transition metal carbene complexes.
      It represents the first example of a 1,2,3-triazolylidene with a 1,2,4
      substitution pattern, thus opening a new subclass ('normal' 1,2,3
      triazolylidenes) of sterically and electronically tunable NHCs.

PMID- 22406928
TI  - Circulating miR-17-5p and miR-20a: molecular markers for gastric cancer.
AB  - Circulating miR-17-5p and miR-20a (miR-17-5p/20a) have been demonstrated to be
      elevated in the plasma of gastric cancer patients. However, the clinical
      significance of the circulating levels of these microRNAs (miRNAs), the
      predictive power for prognosis and application for monitoring of chemotherapeutic
      effects remain unclear. To this end, we measured plasma miR-17-5p/20a levels in
      unpaired pre-operative (n=65), post-operative (n=16) and relapse (n=6) gastric
      cancer patient groups. The 3-year overall survival rate for the unpaired pre
      operative patients was recorded. The circulating levels of miR-17-5p/20a were
      also tested in paired pre-operative and post-operative plasma from 14 gastric
      cancer patients. We found that the concentrations of miR-17-5p/20a were
      significantly associated with the differentiation status and TNM stages of
      gastric cancer. The miRNA levels in the different groups reflected pathological
      tumor progression. Kaplan-Meier curve analysis revealed that high expression
      levels of miR-17-5p/20a were significantly correlated with poor overall survival.
      Cox regression analysis demonstrated that the level of plasma miR-20a was an
      independent risk predictor for prognosis. An in vivo mouse tumor model was
      established and antagomirs against miR-17-5p/20a were applied as
      chemotherapeutics to perform tumor treatment. An assay of serum miR-17-5p/20a
      levels showed that the levels of serum miRNAs were notably reduced in post
      treated mice with tumor volume regression. Taken together, the levels of
      circulating miR-17-5p/20a may be a promising non-invasive molecular marker for
      pathological progression, prediction of prognosis and monitoring of
      chemotherapeutic effects for gastric cancer.

PMID- 22406929
TI  - A rhodamine appended tripodal receptor as a ratiometric probe for Hg2+ ions.
AB  - A new rhodamine appended tripodal receptor 1 has been designed and synthesized.
      The receptor selectively recognizes Hg(2+) ions in CH(3)CN-water (4:1, v/v; 10
      MUM tris HCl buffer, pH 7.0) by displaying a ratiometric change in emission.
      Additionally, the visual detection is possible by a sharp change in color. The
      receptor shows in vitro detection of Hg(2+) ions in human cervical cancer (HeLa)
      cells.

PMID- 22406930
TI  - Survival advantage from ventricular fibrillation and pulseless electrical
      activity in women compared to men: the Oregon Sudden Unexpected Death Study.
AB  - OBJECTIVE: Studies evaluating a possible survival advantage from sudden cardiac
      arrest (SCA) in women have produced mixed results possibly due to a lack of
      comprehensive analyses. We hypothesized that race, socioeconomic status (SES),
      and elements of the lifetime clinical history influence gender effects and need
      to be incorporated within analyses of survival. METHODS: Cases of SCA were
      identified from the ongoing, prospective, multiple-source Oregon Sudden
      Unexpected Death Study (population approximately one million). Subjects included
      were age >=18 years who underwent attempted resuscitation by EMS providers.
      Pearson's chi-square tests and independent samples t tests or analysis of
      variance were used for univariate comparisons. We evaluated gender and race
      differences in survival adjusted for age, circumstances of arrest, disease
      burden, and socioeconomic status using a logistic regression model predicting
      survival. RESULTS: A total of 1,296 cases had resuscitation attempted (2002-2007;
      mean age 65 years, male 67%). Women were older than men (68 vs. 63 years, p <
      0.0001) and were more likely to have return of spontaneous circulation (41% vs.
      33%, p = 0.004). Women were more likely to present with pulseless electrical
      activity (PEA) and asystole (p < 0.0001), and overall, PEA was more common among
      African Americans (p = 0.04). Higher survival to hospital discharge was observed
      in women compared to men presenting with ventricular fibrillation/tachycardia
      (34% vs. 24%, p = 0.02) or with PEA (10% vs. 3%, p = 0.007). In a multivariate
      model adjusting for age, race, presenting arrhythmia, arrest circumstances,
      arrest location, disease burden, and SES, women were more likely than men to
      survive to hospital discharge [odds ratio 1.85; 95% confidence interval (1.12
      3.04)]. CONCLUSIONS: Despite older age, higher prevalence of SCA in the home, and
      higher rates of PEA, women had a survival advantage from ventricular fibrillation
      and pulseless electrical activity.

PMID- 22406931
TI  - Point-by-point pulmonary vein antrum isolation guided by intracardiac
      echocardiography and 3D mapping and duty-cycled multipolar AF ablation: effect of
      multipolar ablation on procedure duration and fluoroscopy time.
AB  - PURPOSE: Pulmonary vein antrum isolation (PVAI) guided by intracardiac
      echocardiography and a roaming circular mapping catheter is an effective
      treatment modality for atrial fibrillation. Unfortunately, the complexity of this
      technique leads to long procedure times and high fluoroscopy exposure. Single
      catheter multipolar ablation holds the promise to reduce these parameters. This
      study examined the effect of the conventional point-by-point PVAI with that of
      single-catheter multipolar ablation on the procedural characteristics and
      clinical outcomes of atrial fibrillation ablation. METHODS: Referred patients
      underwent PVAI guided by a magnetic-based 3D mapping (CARTO 3((r)) System; group
      1) or duty-cycled multipolar AF ablation using the pulmonary vein ablation
      catheter (PVAC, group 2) between June 2010 and May 2011. RESULTS: Data were
      analyzed from 19 patients in group 1 and 31 patients in group 2. There was no
      significant difference in the length of the procedure between the two groups (135
      +/- 26 vs 125 +/- 25 min, P = 0.20). Patients who underwent ablation using PVAC
      spent significantly less time in the procedure room pre- and post-procedure than
      those who underwent conventional PVAI (205 +/- 38 vs 179 +/- 30 min, P = 0.02)
      and had a significantly shorter fluoroscopy exposure (50 +/- 16 vs 36 +/- 14 min,
      P = 0.003) and radiofrequency energy delivery time (54 +/- 26 vs 32 +/- 33 min, P
      = 0.02). No differences in safety and efficacy were seen between the groups.
      CONCLUSIONS: Single-catheter multipolar AF ablation was associated with
      significantly lower fluoroscopy duration, radiofrequency energy delivery time,
      and the time the patient spent in the procedure room before and after ablation,
      although measured short-term clinical outcomes were similar.

PMID- 22406932
TI  - Nanog and Oct4 overexpression increases motility and transmigration of melanoma
      cells.
AB  - PURPOSE: Melanoma tumors are highly heterogeneous and can undergo phenotypic
      modifications depending on their plasticity and the microenvironment, with shifts
      between proliferative and invasive states. We have shown that melanoma cells,
      grown as spheroids in a neural crest cell medium, polarize toward an invasive and
      motile phenotype, in agreement with transcriptomic modulations, including the up
      regulation of Nanog and Oct4. Overexpression of these genes was shown to be
      associated with poor prognosis and metastatic forms of some cancers. We thus
      investigated implication of Nanog and Oct4, two embryonic transcription factors,
      in melanoma motility. METHODS: Our team used stable transfection of Nanog or Oct4
      in A375 melanoma cell line to investigate motility in a wound healing assay and a
      transendothelial migration assay. Using semiquantitative RT-PCR, expression of
      two gene panels involved either in mesenchymal motility or in amoeboid migration
      was studied. RESULTS: Strongly enhanced capacities of motility and extravasation
      were observed with cells overexpressing Oct4 and Nanog. The A375 cell line has
      been described as having a mesenchymal migration type. However, in the Oct4 and
      Nanog transfectants, several amoeboid migration markers are strongly induced.
      Accordingly, amoeboid migration inhibitors decrease significantly the
      transmigration of Oct4- and Nanog-expressing cells through endothelial cells.
      CONCLUSIONS: We propose here that Nanog and Oct4 pluripotency marker expression
      in melanoma cells increases the transmigration capacity of these cells through
      the gain of amoeboid motility, leading to higher invasiveness and aggressiveness.

PMID- 22406933
TI  - Creative spaces in palliative care facilities: tradition, culture, and
      experience.

PMID- 22406934
TI  - Effects of the Rashba spin-orbit coupling on Hofstadter's butterfly.
AB  - We study the effect of Rashba spin-orbit coupling on the Hofstadter spectrum of a
      two-dimensional tight-binding electron system in a perpendicular magnetic field.
      We obtain the generalized coupled Harper spin-dependent equations which include
      the Rashba spin-orbit interaction and solve for the energy spectrum and spin
      polarization. We investigate the effect of spin-orbit coupling on the fractal
      energy spectrum and the spin polarization for some characteristic states as a
      function of the magnetic flux alpha and the spin-orbit coupling parameter. We
      characterize the complexity of the fractal geometry of the spin-dependent
      Hofstadter butterfly with the correlation dimension and show that it grows
      quadratically with the amplitude of the spin-orbit coupling. We study some ground
      state properties and the spin polarization shows a fractal-like behavior as a
      function of alpha, which is demonstrated with the exponent close to unity of the
      decaying power spectrum of the spin polarization. Some degree of spin
      localization or distribution around +1 or -1, for small spin-orbit coupling, is
      found with the determination of the entropy function as a function of the spin
      orbit coupling. The excited states show a more extended (uniform) distribution of
      spin states.

PMID- 22406935
TI  - The multiple effects of tumour necrosis factor inhibitors on immune cells: new
      insights on inhibition of activation and cycling.

PMID- 22406937
TI  - Recurrent epigastric pain with obscure GI bleeding; think beyond the bowel?

PMID- 22406936
TI  - Role of Helicobacter pylori CagL in modulating gastrin expression.

PMID- 22406938
TI  - Long-term graft survival in deep anterior lamellar keratoplasty.
AB  - PURPOSE: To determine corneal graft survival rates up to 10 years in a large
      consecutive series of deep anterior lamellar keratoplasties (DALKs). METHODS: A
      retrospective, consecutive, noncomparative cases series of DALK procedures in a
      total of 806 eyes of 711 patients with stromal diseases and healthy endothelium
      performed between 2000 and 2009. Inclusion criterion was surgery performed by a
      single surgeon (660 eyes), with at least 6 months of follow-up. Graft survival
      was analyzed using the Kaplan-Meier method. Endothelial loss was analyzed with
      the Gaussian distribution and the chi methods. Follow-up time, and preoperative
      and postoperative endothelial cell density (ECD) were considered in the analyses.
      RESULTS: Six hundred sixty eyes of 502 patients met the entry criteria. Mean
      length of follow-up was 4.5 years (range, 0.5-10 years). We report an average
      graft survival rate of 99.3% (range, 98.5%-100%); 3 eyes (0.45%) experienced
      graft failure and 1 eye (0.15%) developed late endothelial failure because of an
      intraoperative complication. Predominant indications for DALK in this series were
      keratoconus (74%), postherpetic keratitis scarring (15%), and corneal stromal
      opacities of different etiology (11%). Endothelial loss from preoperative levels
      averaged 11% (range, 10%-13%) at 6 months through 10 years after DALK. ECD was
      unchanged between 6 months postoperatively and the last follow-up visits.
      CONCLUSIONS: DALK is a successful form of transplantation in stromal corneal
      disorders with healthy endothelium, with higher long-term graft survival rates
      and stable ECD 6 months postoperatively. DALK survival rates do not vary
      significantly over time.

PMID- 22406939
TI  - Incidence of presumed iatrogenic graft failure in Descemet stripping automated
      endothelial keratoplasty.
AB  - PURPOSE: To evaluate presumed iatrogenic graft failure (PIGF) in Descemet
      stripping automated endothelial keratoplasty (DSAEK). METHODS: Deidentified data
      were collected retrospectively from the Illinois Eye Bank between April 2007 and
      May 2010. PIGF was defined as cases in which a repeat corneal transplant was
      performed <8 weeks after an initial DSAEK. Data collected for each case included
      days between initial DSAEK and regraft, regraft type (DSAEK vs. penetrating
      keratoplasty), precut versus surgeon-cut tissue, and number of DSAEKs distributed
      to individual surgeons. Ninety-three cases of PIGF were identified for a group of
      46 surgeons who received 2504 corneas. Nine PIGF cases from 4 surgeons in cornea
      fellowships were analyzed separately. Individual surgeon failure rate and overall
      failure rate were calculated. Analysis of the overall failure rate was conducted
      without cases performed by surgeons who train fellows. Effect of surgical
      experience on PIGF was analyzed. RESULTS: Overall presumed iatrogenic DSAEK
      failure rate was 3.66% (84 PIGF cases divided by 2294 corneas). Within the group
      of 4 surgeons that trained fellows, the failure rate was 4.29% (9 cases PIGF
      divided by 210 corneas). Average time to regraft was 27.5 +/- 17.4 days. Initial
      diagnoses included Fuchs dystrophy, pseudophakic bullous keratopathy, edema, and
      other disease states. Average donor and recipient ages were 54.3 +/- 13.0 and
      71.7 +/- 11.3 years, respectively. Use of precut versus surgeon-cut tissue did
      not affect overall failure rates. Failure rates of less experienced surgeons
      (21.8% +/- 10.8%) were higher than more experienced surgeons (1.5% +/- 1.4%).
      CONCLUSIONS: Overall, DSAEK failure rates improve as surgeons gain experience.
      Failure rates in cornea fellowship programs are not excessive.

PMID- 22406940
TI  - What causes keratoconus?
AB  - PURPOSE: The etiology of keratoconus has been the subject of numerous studies.
      Here, we review the body of literature that attempts to determine what causes
      keratoconus. METHODS: A review of the published literature was performed to
      evaluate the possible causes of keratoconus and how the different etiologies may
      play a role in the development of this disease. RESULTS: Peer-reviewed published
      papers and recent abstracts concerning the different etiologies of keratoconus
      were reviewed and discussed. Biochemical, genetic, and environmental factors are
      reviewed. The role of eye rubbing and atopic disease are explored. CONCLUSIONS:
      We agree with the hypothesis that there is a genetic predisposition that requires
      a "second hit" or environmental event to elicit progressive disease in
      keratoconus. Eye rubbing may serve as the "second hit" in some predisposed
      individuals. Inflammatory mediator studies question if keratoconus is really a
      noninflammatory thinning disorder of the cornea.

PMID- 22406941
TI  - Sociodemographic features and risk factor profile of keratomalacia in early
      infancy.
AB  - PURPOSE: To study the clinical spectrum and etiopathogenesis of keratomalacia in
      infants younger than 6 months. METHODS: Case records of children younger than 6
      months presenting with keratomalacia to cornea services of a tertiary care
      ophthalmic center in India from June 2007 through April 2010 were reviewed. The
      parameters evaluated were age, sex, anthropometry, nutritional status,
      socioeconomic status, antenatal history, maternal nutrition, systemic
      associations, immunization, and dietary history. Comprehensive ocular examination
      with emphasis on ocular adnexa, conjunctiva, cornea, and anterior chamber was
      performed. RESULTS: Overall, 33 infants (24 male and 9 female) with mean age of
      2.8 +/- 1.3 months (range = 1-6 months) were included. Eighty-eight percent (29
      of 33) had associated protein energy malnutrition. A total of 31 of 33 children
      (94%) belonged to poor families, and nearly, three fourth of the children were
      not fully immunized as recommended for their age. Inadequate breastfeeding was
      the precipitating cause in 100%. Maternal nutritional status was poor in 82% of
      the cases. The reason for not breastfeeding the infant was inadequate milk
      production in 89.4% of mothers, 64.7% were ill informed, and 1 mother had adopted
      a child. Feeding practices included diluted cow's milk (1:1-1:5) in 21 infants
      (63.6%), toned dairy milk in 9 infants (27.3%), infant lactogen in 2 infants
      (6.1%), and skimmed milk powder in 1 infant (3.0%). CONCLUSION: Keratomalacia in
      early infancy can be attributed to inadequate breastfeeding. Important
      contributory risk factors include lower socioeconomic status, poor maternal
      nutrition, and lack of knowledge about recommended feeding guidelines.

PMID- 22406942
TI  - The lid wiper contains goblet cells and goblet cell crypts for ocular surface
      lubrication during the blink.
AB  - PURPOSE: The conjunctival side of the upper and lower inner eyelid borders,
      termed the lid wiper, has a thickened epithelial lip for apposition to the globe,
      assumed to distribute the preocular tear film. The human lid wiper structure and
      its goblet cells are investigated. METHODS: Conjunctival whole mounts, including
      lid margins from 17 eyes of human body donors, were investigated by routine
      histology and semithin plastic sections, using histology, histochemistry, and
      immunohistochemistry. RESULTS: In routine histology, the conjunctival lid wiper
      epithelium regularly showed goblet cells, single and in clusters, at the luminal
      surface and also deep within the epithelium without apparent surface contact.
      Semithin sections revealed that the deep goblet cells were often connected to
      cryptal epithelial infoldings that opened to the surface, hence making their
      mucins available at the surface. The goblet cells produced mucins of neutral
      (periodic acid-Schiff) and acidic (Alcian blue) type and stained positive for the
      gel-forming mucin MUC5AC. Surprisingly, MUC5AC-negative goblet cells were also
      observed in the lid wiper. CONCLUSIONS: Contrary to conventional assumptions, the
      lid wiper is part of the conjunctiva. It contains previously undescribed goblet
      cell crypts deep in the epithelium, suitable as an internal lubrication system
      for reduction of friction between the lid margin and the globe. This provides the
      first evidence of the morphological basis for the hydrodynamic type of
      lubrication and a more conclusive understanding of lid-margin lubrication and
      tear film distribution. It is another strong indication that the lid wiper is
      that area in apposition with the globe for distributing the thin preocular tear
      film during the blink.

PMID- 22406943
TI  - Comparison of the long-term effects of various topical antiglaucoma medications
      on meibomian glands.
AB  - PURPOSE: To examine the effects of long-term antiglaucoma eye drop treatment on
      meibomian glands. METHODS: The subjects were 71 eyes of 71 glaucoma patients
      (group 1) receiving one type of antiglaucoma eye drops, 61 eyes of 61 glaucoma
      patients (group 2) receiving two types of antiglaucoma eye drops, and 30 eyes of
      30 glaucoma patients (group 3) receiving three types of antiglaucoma eye drops.
      Controls comprised 75 eyes of 75 healthy volunteers. Subjective symptoms were
      evaluated by questionnaire, and lid margin and superficial punctate keratopathy
      were evaluated by slit lamp examination. Meibomian glands of upper and lower
      eyelids were observed and scored using noncontact meibography (meiboscore). Tear
      film break-up time (BUT) was measured and meibum was graded. RESULTS: Lid margin
      abnormality, superficial punctate keratopathy, meiboscore, and meibum scores were
      significantly higher in glaucoma patients than in controls (P < 0.001). BUT and
      Schirmer scores were significantly lower in glaucoma patients than in controls (P
      < 0.001). Subgroup analysis of the parameters in group 1 revealed no significant
      difference between patients receiving prostaglandin and those receiving beta
      blockers, or among groups 1, 2, and 3. Multivariate regression analysis
      demonstrated that meiboscore significantly correlated with lid margin abnormality
      score (P = 0.007) and BUT (P = 0.045) in group 1; with BUT (P = 0.004), symptom
      score (P = 0.003), and age (P = 0.026) in group 2; and with lid margin
      abnormality score (P = 0.001) in group 3. CONCLUSIONS: Long-term use of
      antiglaucoma eye drops was associated with alterations in meibomian gland
      morphology and function.

PMID- 22406944
TI  - The modified Cincinnati procedure: combined conjunctival limbal autografts and
      keratolimbal allografts for severe unilateral ocular surface failure.
AB  - PURPOSE: To describe the technique and present the outcomes of combined
      conjunctival limbal autografts (CLAU) and keratolimbal allografts (KLAL) for the
      treatment of unilateral severe ocular surface failure. METHODS: Interventional
      case series. Eleven eyes of 11 patients who sustained chemical burns (4 alkali
      and 2 acid) and combined chemical/thermal burns (5 eyes) from firework explosions
      had combined CLAU/KLAL surgery. Keratoplasty was performed subsequently for
      residual corneal stromal scarring limiting visual acuity. Inclusion criteria
      included eyes with severe unilateral total ocular surface failure, controlled
      glaucoma, and reasonable eyelid apposition with no exposure. Exclusion criteria
      included patients with any ocular surface abnormality in the fellow eye and those
      with contraindications to systemic immunosuppression (SI). Outcome measures
      included Snellen best-corrected visual acuity (BCVA), ocular surface stability,
      SI exposure, and complications. RESULTS: Preoperative BCVA was 20/400 or worse in
      all eyes. At the final follow-up (mean, 35.8 months; range, 12.1-105.9 months),
      73% (8 of 11) eyes had BCVA of 20/80 or better (range, 20/25 to counting
      fingers), and ocular surface was stable in 82% (9 of 11). Ninety-one percent (10
      of 11) had additional penetrating keratoplasty (PK) with a 60% (6 of 10 eyes)
      success rate. Three cases had subsequent Boston type 1 keratoprosthesis
      implantation after PK failure, and the fourth patient, at the time of his last
      follow-up visit, did not want further intervention for his edematous PK, which
      was a result of noncompliance-related corneal rejection. In eyes with more than 2
      years of follow-up, SI was tapered at a mean of 16 months (range, 8-28 months).
      There were no intraoperative complications. No secondary tumors, cardiac events,
      or deaths occurred while patients were on SI. One patient developed secondary
      glaucoma refractory to medical management after subsequent PK, requiring
      cyclodiode laser. CONCLUSIONS: Combined CLAU/KLAL and staged keratoplasty is
      effective in improving vision and maintaining long-term ocular surface stability
      in patients with severe unilateral ocular surface disease and conjunctival
      deficiency.

PMID- 22406945
TI  - Improved wound stability of top-hat profiled femtosecond laser-assisted
      penetrating keratoplasty in vitro.
AB  - PURPOSE: The femtosecond laser is a new option for cutting corneal tissue at high
      precision. The "top-hat" profile has an overlapping graft-host interface at the
      edge because of a larger inner trephination diameter. This may enhance graft
      fixation, thus improving the outcome and accelerating rehabilitation after
      penetrating keratoplasty. METHODS: Femtosecond laser top-hat keratoplasties with
      overlaps of 0 and 3 mm between inner and outer trephination diameters were
      performed in vitro. After trephination, the excised corneal buttons were
      readapted by different suturing profiles. Pressure in the artificial anterior
      chamber was then raised until we observed wound leakage and ultimately wound
      prolapse. RESULTS: Better wound stability was found in conjunction with all
      profiled trephinations. When using 4 interrupted sutures, wound leakage occurred
      at a median of 13.0 cm H2O (mean, 12.3 cm H2O) and "zero overlap," at 19.0 cm H2O
      (mean, 20.8 cm H2O) and 1-mm overlap, at 32.0 cm H2O (mean, 32.8 cm H2O) and 2-mm
      overlap, and at 48.5 cm H2O (mean, 49.4 cm H2O) and 3-mm overlap. Comparing zero
      overlap with the mean values of 1- to 3-mm overlaps, wound leakage happened at
      13.0 (mean, 12.3) versus 32.0 (mean, 34.3) cm H2O with 4 interrupted sutures, at
      57.5 (mean, 58.3) versus 61.0 (mean, 70.8) cm H2O with 8 interrupted sutures, at
      31.5 (mean, 32.0) versus >97.0 (mean, 75.5) cm H2O with 1 running and 4
      interrupted sutures, and at 34.0 (mean, 32.3) versus 80.0 (mean, 69.9) cm H2O
      with 1 running suture. The analysis of variance revealed a statistically
      significant increase in wound stability for all overlaps independently from the
      size of the overlap. CONCLUSIONS: Femtosecond laser-assisted profiles with even
      small overlaps for penetrating keratoplasty may make fewer sutures and earlier
      suture removal possible because of better wound stability, contributing to
      earlier visual recovery and helping to prevent wound rupture after trauma.
      However, further study is required to identify the optimum profile including the
      various technical parameters.

PMID- 22406946
TI  - Linear interstitial keratitis:  a distinct clinical entity revisited.
AB  - PURPOSE: Few reports in the ophthalmic literature describe rare corneal lesions
      of the stroma that present in a horizontal linear fashion. Although some
      differences exist among the small number of reported cases, we believe that all
      these cases represent a distinct clinical entity appropriately titled linear
      interstitial keratitis. In an attempt to expand the knowledge of this condition
      of unknown etiology, we present 3 cases of linear interstitial keratitis.
      METHODS: Case series (3 cases are presented) and literature review. RESULTS: All
      3 patients (aged 21-22 years) presented with horizontal linear stromal
      infiltrates. One patient presented with a corneal perforation, requiring a
      closure with 3 interrupted sutures. Another patient required a penetrating
      keratoplasty because of a visually significant central scar. All 3 patients
      responded to topical steroids. CONCLUSIONS: Linear interstitial keratitis is a
      rare clinical entity and its histopathologic etiology remains undetermined.
      Current available technology including specular microscopy, anterior segment
      optical coherence tomography, and more sensitive serological testing may permit a
      better understanding of this disease.

PMID- 22406947
TI  - Paste-pinch-cut conjunctivoplasty:  subconjunctival fibrin sealant injection in
      the repair of conjunctivochalasis.
AB  - PURPOSE: To describe a new surgical technique for the repair of
      conjunctivochalasis (CCh) using subconjunctival injection of fibrin sealant
      followed by conjunctival resection and to present a case series demonstrating our
      experience with the paste-pinch-cut technique. METHODS: A total of 139 eyes of 70
      patients (43 women, 27 men) with CCh unresponsive to medical therapy received the
      described surgical treatment. The procedure consists of 3 primary steps-paste:
      fibrin sealant is injected subconjunctivally in a line inferior to the limbus;
      pinch: the conjunctiva is grasped with curved ptosis forceps, gathering the
      excess conjunctiva into a ridge, which is held, allowing the sealant to
      polymerize; and cut: the ridge of excess conjunctiva and sealant is resected.
      Subjective symptoms were assessed after surgery. RESULTS: Conjunctival redundancy
      was absent postoperatively in all eyes, resulting in a smooth conjunctival
      surface and restored tear meniscus. At the 3-month follow-up visit, 91.4% of
      patients reported improvement in symptoms. There were no recurrences or
      significant complications. CONCLUSIONS: The present retrospective,
      noncomparative, consecutive, interventional case series study introduces paste
      pinch-cut conjunctivoplasty as a simple and an effective surgical treatment for
      the repair of CCh in symptomatic patients.

PMID- 22406948
TI  - Effect of chitinase on resistance to fungal pathogens in sea buckthorn, Hippophae
      rhamnoides, and cloning of Class I and III chitinase genes.
AB  - Sea buckthorn (Hippophae rhamnoides L.) is naturally distributed from Asia to
      Europe. It has been widely planted as an ornamental shrub and is rich in
      nutritional and medicinal compounds. Fungal pathogens that cause diseases such as
      dried-shrink disease are threats to the production of this plant. In this study,
      we isolated the dried-shrink disease pathogen from bark and total chitinase
      protein from leaves of infected plants. The results of the Oxford Cup experiment
      suggested that chitinase protein inhibited the growth of this pathogen. To
      improve pathogen resistance, we cloned chitinase Class I and III genes in H.
      rhamnoides, designated Hrchi1 and Hrchi3. The full-length cDNA of the open
      reading frame region of Hrchi1 contained 903 bp encoding 300 amino acids and
      Hrchi3 contained 894 bp encoding 297 amino acids. Active domain analysis, protein
      types, and secondary and 3D structures were predicted using online software.

PMID- 22406951
TI  - Beyond the palaeomicrobiology.
AB  - This month's Genome Watch highlights the power of palaeomicrobiology in
      extracting detailed information about the genomes of ancient microorganisms.

PMID- 22406953
TI  - Comparison between homologous human milk supplements and a commercial supplement
      for very low birth weight infants.
AB  - OBJECTIVES: To describe the methodology for the preparation of two additives
      derived from human milk, liquid and powdered, and to compare this composition
      with the commercial additive FM85(r). METHODS: For the preparation of the liquid
      and powdered supplements, 40 samples of human milk were used. Both supplements
      have been through three preparation phases: skimming, evaporation and lactose
      removal. After these phases, the liquid supplement is ready, and the powdered
      requires a fourth phase - lyophilization. To each sample of the liquid and
      powdered supplements were added, respectively, 80 mL (group I) and 100 mL (group
      II) of pooled banked human milk. For comparison, 20 samples of 100 mL of the pool
      were added to 5 g of the FM85(r) supplement (Nestle) (group III). Analyses of
      carbohydrates, protein, lipids, calcium, phosphorus, sodium, osmolality and
      caloric content were performed, considering a significant difference p < 0.05.
      RESULTS: Groups I, II, and III showed, respectively, the following results:
      protein = 1.81, 2.38 and 1.96 g/dL (p < 0.001); carbohydrates = 6.70, 7.25 and
      10.06 g/dL (p = 0.006); fat = 3.75, 3.75 and 3.73 g/dL (p = 0.96); calcium =
      36.92, 44.75 and 79.37 mg/dL (p = 0.001); phosphorus = 20.02, 23.28 and 56.30
      mg/dL (p = 0.02); sodium = 14.32, 14.40 and 20.33 mEq/L (p = 0.143); osmolality =
      391.45, 412.47 and 431.00 mOsmol/kgH(2)O (p = 0.074); and caloric content =
      67.78, 72.27 and 81.65 kcal (p = 0.001). CONCLUSION: The studied additives differ
      significantly from the commercial additive FM85(r) in some of its components, and
      its composition may or may not meet the quantity of nutrients suggested by the
      most recent recommendations.

PMID- 22406954
TI  - Fine mapping of fw3.2 controlling fruit weight in tomato.
AB  - Tomato (Solanum lycopersicum) is an important crop in the Solanaceae family. One
      of the key traits selected during domestication is fruit mass which is controlled
      by many quantitative trait loci. The fruit weight locus fw3.2 is one of the major
      loci responsible for fruit mass in tomato. Identification of the underlying gene
      will improve our understanding of the molecular mechanism of fruit development
      while also providing insights into genes that were selected during domestication.
      We fine mapped fw3.2 to a 51.4-kb interval corresponding to a region comprising
      seven candidate genes. Gene action showed that the allele from cultivated tomato
      was additive to dominant in giving rise to an enlarged fruit. Fruit shape
      analysis indicated that fw3.2 primarily played a role in controlling fruit
      weight, with a minor effect on fruit shape. Gene expression and nucleotide
      diversity were investigated and the likelihood of the genes control fruit mass is
      discussed.

PMID- 22406955
TI  - Co-mapping studies of QTLs for fruit acidity and candidate genes of organic acid
      metabolism and proton transport in sweet melon (Cucumis melo L.).
AB  - Sweet melon cultivars contain a low level of organic acids and, therefore, the
      quality and flavor of sweet melon fruit is determined almost exclusively by fruit
      sugar content. However, genetic variability for fruit acid levels in the Cucumis
      melo species exists and sour fruit accessions are characterized by acidic fruit
      pH of <5, compared to the sweet cultivars that are generally characterized by
      mature fruit pH values of >6. In this paper, we report results from a mapping
      population based on recombinant inbred lines (RILs) derived from the cross
      between the non-sour 'Dulce' variety and the sour PI 414323 accession. Results
      show that a single major QTL for pH co-localizes with major QTLs for the two
      predominant organic acids in melon fruit, citric and malic, together with an
      additional metabolite which we identified as uridine. While the acidic
      recombinants were characterized by higher citric and malic acid levels, the non
      acidic recombinants had a higher uridine content than did the acidic
      recombinants. Additional minor QTLs for pH, citric acid and malic acid were also
      identified and for these the increased acidity was unexpectedly contributed by
      the non-sour parent. To test for co-localization of these QTLs with genes
      encoding organic acid metabolism and transport, we mapped the genes encoding
      structural enzymes and proteins involved in organic acid metabolism, transport
      and vacuolar H+ pumps. None of these genes co-localized with the major pH QTL,
      indicating that the gene determining melon fruit pH is not one of the candidate
      genes encoding this primary metabolic pathway. Linked markers were tested in two
      additional inter-varietal populations and shown to be linked to the pH trait. The
      presence of the same QTL in such diverse segregating populations suggests that
      the trait is determined throughout the species by variability in the same gene
      and is indicative of a major role of the evolution of this gene in determining
      the important domestication trait of fruit acidity within the species.

PMID- 22406956
TI  - Clinical and biologic features of patients suspected or confirmed to have heparin
      induced thrombocytopenia in a cardiothoracic surgical ICU.
AB  - BACKGROUND: The diagnosis of heparin-induced thrombocytopenia (HIT) is
      problematic in the surgical ICU, as there are multiple potential explanations for
      thrombocytopenia. We conducted a study to assess the incidence, clinical
      presentation, and outcome of HIT in a cardiothoracic surgical ICU. METHODS: From
      January 2005 to December 2010, all patients with suspicion of HIT were
      prospectively identified, and data were collected retrospectively. Detection of
      anti-PF4/heparin antibodies and functional assays were systematically performed.
      RESULTS: During the study period, 5,949 patients were admitted to the ICU (2,751
      after cardiac surgery and 3,198 after thoracic surgery), of whom 101 were
      suspected to have HIT(1.7% [95% CI, 1.4%-2.0%]). Suspicion of HIT occurred at a
      median of 5 (4-9) days after ICU admission. Diagnosis was confirmed in 28 of
      5,949 patients (0.47% [95% CI, 0.33%-0.68%]).Thrombosis was detected in 14
      patients with HIT (50%) and in 12 patients without HIT (16%)( P 5 .0006). After
      receiver operating characteristic analysis (area under curve 5 0.78 0.06),a 4Ts
      score >= 5 had a sensitivity of 86% and a specificity of 70%. Course of platelet
      count was similar between the two groups. Six patients (21%) with HIT and 20
      (27%) without died( P 5 .77). CONCLUSIONS: Even with a prospective platelet
      monitoring protocol, suspicion for HIT arose in <2% of patients in a
      cardiothoracic ICU. Most were found to have other causes of thrombocytopenia,with
      HIT confirmed in 28 of 101 suspected cases (0.47% of all patients in the ICU).
      The 4Ts score may have value by identifying patients who should have laboratory
      testing performed.The mortality of patients with HIT was not different from other
      very ill thrombocytopenic patients in the ICU.

PMID- 22406957
TI  - Obstructive sleep apnea is associated with increased high-sensitivity cardiac
      troponin T levels.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased
      cardiovascular risk. Stress imposed on the myocardium by repeated severe
      hypoxemia and/or BP surges during sleep may result in subclinical myocardial
      injury. A high-sensitivity cardiac troponin T (hs-cTnT) assay has been developed.
      We hypothesized that the severity of OSA, as assessed by the apnea-hypopnea index
      (AHI), is associated with circulating levels of hs-cTnT in the general
      population. METHODS: Five hundred five subjects drawn from the general population
      (age range, 30-65 years; 45% women) underwent in-hospital polysomnography and had
      morning blood samples drawn. Oversampling of subjects at high risk of OSA was
      performed. RESULTS: Overall, hs-cTnT was detectable (>= 3 ng/L) in 216 subjects
      (42.8%). After categorizing subjects according to AHI cutoffs that correspond to
      no, mild to moderate, and severe OSA, the proportion of subjects with detectable
      hs-cTnT levels increased with increasing severity of OSA (P for trend < .001).
      Multivariate logistic regression with detectable hs-cTnT as the dependent
      variable was used to further assess the association between OSA and troponin T.
      After adjustment for significant univariate predictors of detectable hs-cTnT, the
      association between AHI and hs-cTnT was no longer statistically significant.
      CONCLUSIONS: The prevalence of detectable hs-cTnT increases in proportion to OSA
      severity, but this association is likely to be caused by a clustering of
      cardiovascular risk factors among subjects with OSA.

PMID- 22406958
TI  - Patient-ventilator asynchrony during noninvasive ventilation: a bench and
      clinical study.
AB  - BACKGROUND: Different kinds of ventilators are available to perform noninvasive
      ventilation (NIV) in ICUs. Which type allows the best patient-ventilator
      synchrony is unknown. The objective was to compare patient-ventilator synchrony
      during NIV between ICU, transport-both with and without the NIV algorithm engaged
      and dedicated NIV ventilators. METHODS: First, a bench model simulating
      spontaneous breathing efforts was used to assess the respective impact of
      inspiratory and expiratory leaks on cycling and triggering functions in 19
      ventilators. Second, a clinical study evaluated the incidence of patient
      ventilator asynchronies in 15 patients during three randomized, consecutive, 20
      min periods of NIV using an ICU ventilator with and without its NIV algorithm
      engaged and a dedicated NIV ventilator. Patient-ventilator asynchrony was
      assessed using flow, airway pressure, and respiratory muscles surface
      electromyogram recordings. RESULTS: On the bench, frequent auto-triggering and
      delayed cycling occurred in the presence of leaks using ICU and transport
      ventilators. NIV algorithms unevenly minimized these asynchronies, whereas no
      asynchrony was observed with the dedicated NIV ventilators in all except one.
      These results were reproduced during the clinical study: The asynchrony index was
      significantly lower with a dedicated NIV ventilator than with ICU ventilators
      without or with their NIV algorithm engaged (0.5% [0.4%-1.2%] vs 3.7% [1.4%
      10.3%] and 2.0% [1.5%-6.6%], P < .01), especially because of less auto
      triggering. CONCLUSIONS: Dedicated NIV ventilators allow better patient
      ventilator synchrony than ICU and transport ventilators, even with their NIV
      algorithm. However, the NIV algorithm improves, at least slightly and with a wide
      variation among ventilators, triggering and/or cycling off synchronization.

PMID- 22406959
TI  - Incidence and cost of pneumonia in medicare beneficiaries.
AB  - BACKGROUND: Pneumonia is a frequent and serious illness in elderly people, with a
      significant impact on mortality and health-care costs. Lingering effects may
      influence clinical outcomes and medical service use beyond the acute
      hospitalization. This study describes the incidence and mortality of pneumonia in
      elderly Medicare beneficiaries based on treatment setting (outpatient, inpatient)
      and location of origin (health-care associated, community acquired) and estimates
      short- and long-term direct medical costs and mortality associated with an
      inpatient episode of pneumonia. METHODS: Administrative claims from a 5% sample
      of fee-for-service Medicare beneficiaries aged >= 65 years from 2005 through 2007
      were used. Total direct medical costs for patients during and after
      hospitalization for pneumonia compared with similar patients without pneumonia
      (the excess cost of pneumonia) were estimated using propensity score matching.
      RESULTS: The age-adjusted annual cumulative incidence of any pneumonia was 47.4
      per 1,000 beneficiaries (13.3 per 1,000 inpatient primary pneumonia), increasing
      with age; one-half of pneumonia cases were treated in the hospital. Thirty-day
      mortality was twice as high among beneficiaries with health-care-associated
      pneumonia than among those hospitalized with community-acquired pneumonia (13.4%
      vs 6.4%). Total medical costs for beneficiaries during and 1 year following a
      pneumonia hospitalization were $15,682 higher than matched control patients
      without pneumonia. The total annual excess cost of hospital-treated pneumonia as
      a primary diagnosis in the elderly fee-for-service Medicare population in 2010 is
      estimated conservatively at > $7 billion. CONCLUSIONS: Pneumonia in elderly
      people is associated with high acute-care costs and an overall impact on total
      direct medical costs and mortality during and after an acute episode.

PMID- 22406960
TI  - Indwelling pleural catheters reduce inpatient days over pleurodesis for malignant
      pleural effusion.
AB  - BACKGROUND: Patients with malignant pleural effusion (MPE) have limited
      prognoses. They require long-lasting symptom relief with minimal hospitalization.
      Indwelling pleural catheters (IPCs) and talc pleurodesis are approved treatments
      for MPE. Establishing the implications of IPC and talc pleurodesis on subsequent
      hospital stay will influence patient choice of treatment. Therefore, our
      objective was to compare patients with MPE treated with IPC vs pleurodesis in
      terms of hospital bed days (from procedure to death or end of follow-up) and
      safety. METHODS: In this prospective, 12-month, multicenter study, patients with
      MPE were treated with IPC or talc pleurodesis, based on patient choice. Key end
      points were hospital bed days from procedure to death (total and effusion
      related). Complications, including infection and protein depletion, were
      monitored longitudinally. RESULTS: One hundred sixty patients with MPE were
      recruited, and 65 required definitive fluid control; 34 chose IPCs and 31
      pleurodesis. Total hospital bed days (from any causes) were significantly fewer
      in patients with IPCs (median, 6.5 days; interquartile range [IQR] = 3.75-13.0 vs
      pleurodesis, mean, 18.0; IQR, 8.0-26.0; P = .002). Effusion-related hospital bed
      days were significantly fewer with IPCs (median, 3.0 days; IQR, 1.8-8.3 vs
      pleurodesis, median, 10.0 days; IQR, 6.0-18.0; P < .001). Patients with IPCs
      spent significantly fewer of their remaining days of life in hospital (8.0% vs
      11.2%, P < .001, chi(2) = 28.25). Fewer patients with IPCs required further
      pleural procedures (13.5% vs 32.3% in pleurodesis group). There was no difference
      in rates of pleural infection (P = .68) and protein (P = .65) or albumin loss (P
      = .22). More patients treated with IPC reported immediate (within 7 days)
      improvements in quality of life and dyspnea. CONCLUSIONS: Patients treated with
      IPCs required significantly fewer days in hospital and fewer additional pleural
      procedures than those who received pleurodesis. Safety profiles and symptom
      control were comparable.

PMID- 22406961
TI  - Independent association of urinary F2-isoprostanes with survival in pulmonary
      arterial hypertension.
AB  - OBJECTIVES: Within the past decade, biochemical markers have emerged as
      attractive tools to assess pulmonary arterial hypertension (PAH) prognosis, being
      noninvasive and easily repeatable.The objective of this study was to determine
      whether biomarkers measured at initial diagnostic right-sided heart
      catheterization predict 3-year all-cause mortality for incident cases of PAH
      independently of clinical and hemodynamic parameters. METHODS: Patients with
      incident PAH were enrolled between December 2003 and April 2006 in six centers
      from the French Network on Pulmonary Hypertension and followed for 3 years.Venous
      blood samples were taken during right-sided heart catheterization, and analyses
      were centralized. RESULTS: Among 110 enrolled patients, 11 underwent lung or
      heart/lung transplantation, and 27 died during follow-up. The Kaplan-Meier
      estimates of survival were 91%, 78%, and 75% at 1, 2, and 3 years, respectively.
      Plasma big endothelin-1 (hazard ratio [HR] per 1-SD increase, 1.48; 95% CI,1.14
      1.92), serum troponin T . 0.01 mg/L (HR, 2.35; 95% CI, 1.05-5.29), and urinary F
      2 -isoprostanes(15-F2t -isoprostane) (HR per 1-SD increase, 1.76; 95% CI, 1.31
      2.36) were associated with increased unadjusted hazard of death. In multivariate
      analysis adjusting for patient characteristics, the level of urinary F 2 
      isoprostanes was the only biomarker that remained independently associated with
      increased hazard of death (HR per 1-SD increase, 1.82; 95% CI, 1.28-2.60).
      CONCLUSIONS: This study shows that levels of urinary F 2 -isoprostane, a
      biomarker of lipid peroxidation,quantified at initial diagnostic right-sided
      heart catheterization are independently associated with mortality in a cohort of
      patients with incident PAH.

PMID- 22406962
TI  - Guest editors' introduction to feature section: bariatric surgery.

PMID- 22406963
TI  - Readmission to the intensive care unit after cardiac surgery: a single-center
      experience with 7105 patients.
AB  - AIM: Identification of patients at high risk for readmission to the Intensive
      Care Unit (ICU) after cardiac surgery is paramount. We evaluated the clinical
      characteristics of readmitted patients and identified perioperative prognostic
      variables for ICU readmission. METHODS: A total of 7105 patients who underwent
      cardiac surgery between 2007 and 2010 and discharged after a primary stay in the
      ICU were reviewed retrospectively. Of these, 7.8% (554) patients were readmitted.
      The reasons for readmission and postoperative course were analyzed. Perioperative
      risk factors for readmission were determined by multivariate regression analysis.
      RESULTS: Mortality of patients after readmission was 13.6% compared with 0.2%
      without recidivism (P<0.0001). Mean length of stay in hospital of patients
      requiring readmission was 24.9 +/- 19.1 days and significantly longer compared to
      all other patients 12.3+/-8.4 days (P<0.0001). The main reasons for readmission
      were respiratory failure (39.0%) and cardiovascular instability (26.2%). Complex
      cardiac surgery, aortic surgery and extended stay in the ICU were the most
      powerful variables to predict ICU readmission. CONCLUSION: ICU readmission was
      related to complex surgery and associated with impaired outcome. Respiratory
      complications were the most common reasons for readmission. Predictive renal and
      pulmonary risk factors indicate the need of preoperative preconditioning and
      patient selection.

PMID- 22406964
TI  - Conventional carotid endarterectomy versus stenting: comparison of restenosis
      rates in arteries with identical predisposing factors.
AB  - AIM: The aim of the study was to investigate the possible role of individual
      predisposition in the pathogenesis of carotid restenosis. METHODS:Over 1700
      patients have undergone carotid endarterectomy (CEA) in our institute over the
      past 15 years. We retrospectively reviewed the charts of those who also had
      contralateral carotid stenting (CAS) for primary atherosclerotic stenosis and
      recorded the rates of post-CEA and post-CAS restenosis >=50%. RESULTS: In the 29
      cases analyzed (21 men/8 women), CEA was performed with conventional technique
      and direct suturing in most cases. Mean ages at the time of CEA and CAS were
      69.2+/-6.6 and 73+/-6.7 yrs, respectively, and risk profiles at the 2 time points
      were similar: hypertension (96.5%), dyslipidemia (55.2%), smoking (51.7%),
      diabetes (31%), coronary artery disease (48.3%), chronic obstructive pulmonary
      disease (37.9%), and chronic renal failure (13.8%). Antiplatelet therapy
      protocols were identical for the two procedures. During follow-up (mean: 67.25+/
      51.6 months after CEA, 24.6+/-16.9 months after CAS), Duplex scans revealed
      restenosis in 12 patients (9 arteries treated with CEA, 6 managed with CAS). In
      three patients, restenosis was bilateral. Restenosis-free survival rates at five
      years were 85% after CEA and 66% after CAS (P=NS). CONCLUSION: In this selected
      group of patients, CEA and CAS were associated with a similar incidence of
      restenosis. Only 25% of the patients who developed restenosis did so after both
      procedures. These preliminary findings indicate that individual predisposition
      does not play a crucial role in the pathogenesis of restenosis. To confirm this
      conclusion, an analysis of a much larger, multicenter cohort is essential.

PMID- 22406965
TI  - Can the opportunity of cardio-pulmonary bypass be useful in complex general
      thoracic surgery problems? A report of nine cases.
AB  - AIM: We report on nine highly selected patients in whom the resection of the
      tumor was only possible with cardiopulmonary bypass (CPB). METHODS: Between
      November 1996 and November 2009, nine patients with non-cardiac tumors underwent
      surgery under CPB. Indications were: infiltration of the pulmonary vein in the
      left atrium (four cases), one case where the tumor (a paraganglioma apparently
      located in the subcarinal space) was actually in the atrium wall, one mediastinal
      liposarcoma with massive infiltration of the pericardium and the main pulmonary
      artery, and three tracheal tumors (2 cylindromas and 1 carcinoid). RESULTS:
      Indication for CPB was decided preoperatively in 7 cases and intraoperatively in
      the other 2 patients. Cardiac infiltration was confirmed with intraoperative
      transesophageal cardiac echography in 2 patients, which proved to be very useful.
      Concerning postoperative complications, one patient died intraoperatively because
      it was impossible to stop the CPB after reconstruction of the bifurcation of the
      main pulmonary artery. Although the duration of the operation was significantly
      increased by the use of cardiopulmonary by-pass, it did not influence
      postoperative recovery in any of the other eight patients, as far as bleeding or
      infection was concerned. In one patient, a thoracic drain had to be replaced due
      to a partial pneumothorax. In another patient a partial dehiscence of the neo
      carina was conservatively treated. Long-term results were influenced by the
      initial pathology of the patient. CONCLUSION: CPB provides the possibility of
      safely resecting intrathoracic tumors invading cardiac structures that were
      previously inoperable. This can be achieved with an acceptable level of risk and 
      in very selected cases - may achieve long-term survival.

PMID- 22406966
TI  - Abdominal aortic aneurysms with short proximal neck: comparison between standard
      endograft and open repair.
AB  - AIM: Comparing the results of the treatment of abdominal aortic aneurysms (AAA)
      with infra-renal neck length <=1 cm with open repair (OR) and with endovascular
      treatment (EVAR) with standard endograft. METHODS: Patients treated from January
      2005 to December 2009 for infra-renal AAA with neck length <=1 cm, were
      prospectively included. The choice of treatment was made up on anatomical and
      clinical criteria. Cases treated with OR (G1) and EVAR (G2) were compared.
      Primary end-points were: peri-operative mortality/morbidity and re-interventions,
      renal function worsening at discharge, mortality and re-interventions during
      follow-up. Secondary end points were: procedure time, need and time of intensive
      unit care (IUC) hospitalization, need for blood transfusions and hospital days.
      The comparison between groups was estimated by the Long-rank test. RESULTS:
      Eighty-two patients were treated (76 males and 6 females); the mean age was 71.4
      years (range 56-86) and the mean AAA diameter was 6.2 cm. Forty-four patients
      were enrolled in G1 and 38 in G2. The two groups were clinically homogeneous,
      except for: age (G1<G2: P<0.001), chronic obstructive pulmonary disease (COPD)
      (G1<G2: P=0.016) and obesity (G1<G2: P=0.045). The mean follow-up was 26 months
      (range 1-63.6). The overall operative mortality was 3.7%: all deaths (3 cases)
      occurred in G1 (6.8%) while no deaths occurred in G2 (P=NS). The association of
      peri-operative morbidity and mortality was higher in G1 (P=0.012). There were 7
      peri-operative re-interventions, 4 in G1 (9%) and 3 in G2 (7.8%) (P=NS). There
      was no statistical difference in renal function worsening at discharge between
      the two groups. At 36 months overall survival was 84% and the survival of G1 and
      G2 was respectively 80.5% and 87.4% (P=NS). At 36 months, freedom from re
      intervention was 82.6% in G1 and 88.4% in G2 (P=NS). All the secondary end points
      were significantly better in G2. CONCLUSION: These results show that EVAR with
      standard endograft is an effective and reliable option in AAA with neck length
      <=1 cm in short and mid-term follow-up. Long-term follow-up results are needed.

PMID- 22406967
TI  - Diagnostics of primary aldosteronism: is obligatory use of confirmatory tests
      justified?
AB  - INTRODUCTION: Assessment of the renin-angiotensin-aldosterone system has been
      recently granted a much greater role in the evaluation of patients with arterial
      hypertension. There is no single test efficient in selection of patients for
      second-step etiological investigation. METHODS: Altogether, 198 consecutive
      patients--119 women (60%) and 79 men (40%)--hospitalized in years 2009-2011 at
      the Clinical Department of Endocrinology Medical University of Bialystok were
      diagnosed with primary aldosteronism. In each patient, plasma renin activity and
      plasma aldosterone concentration (basic and after 2 l NaCl infusion) were
      evaluated. RESULTS: The percentage of patients with plasma aldosterone
      concentration >= 15 ng/ml was 53 and the percentage of patients with plasma renin
      activity <= 0.1 ng/ml/h was 20. The percentage of patients screened for primary
      aldosteronism in which the aldosterone:renin ratio exceeded consecutive cut-offs
      of 20, 30, 40 and 50 were respectively 57, 45, 34 and 29. Among 15 patients in
      which plasma aldosterone concentration after infusion of 2 l of saline was >= 6.5
      ng/dl (8.6%), 13 (6.6%) were diagnosed with primary aldosteronism. CONCLUSION:
      The obligatory use of tests confirming autonomy of aldosterone secretion in
      patients screened for primary aldosteronism seems cost-effective in limiting the
      number of patients for further diagnosis.

PMID- 22406968
TI  - Representativeness of participants in the cancer care outcomes research and
      surveillance consortium relative to the surveillance, epidemiology, and end
      results program.
AB  - BACKGROUND: The research goals of the Cancer Care Outcomes Research and
      Surveillance (CanCORS) Consortium are to determine how characteristics and
      beliefs of patients, providers, and health care organizations influence the
      treatments and outcomes of individuals with newly diagnosed lung and colorectal
      cancers. As CanCORS results will inform national policy, it is important to know
      how they generalize to the United States population with these cancers. RESEARCH
      DESIGN: This study assessed the representativeness of the CanCORS cohort of
      10,547 patients with lung cancer (LC) or colorectal cancer (CRC) enrolled between
      2003 and 2005. We compared characteristics (sex, race, age, and disease stage)
      with the Surveillance, Epidemiology, and End Results (SEER) population of 234,464
      patients with new onset of these cancers during the CanCORS recruitment period.
      RESULTS: The CanCORS sample is well matched to the SEER Program for both cancers.
      In CanCORS, 41% LC/47% CRC were female versus 47% LC/49% CRC in SEER. African
      American, Hispanic, and Asian cases differed by no more than 5 percentage points
      between CanCORS and SEER. The SEER population is slightly older, with the
      percentage of patients older than 75 years 33.1% LC/37.3% CRC in SEER versus
      26.9% LC/29.4% in CanCORS, and also has a slightly higher proportion of early
      stage patients. We also found that the CanCORS cohort was representative within
      specific SEER regions that map closely to CanCORS sites. CONCLUSIONS: This study
      demonstrates that the CanCORS Consortium was successful in enrolling a
      demographically representative sample within the CanCORS regions.

PMID- 22406969
TI  - Theoretical studies on the interaction of biphenyl inhibitors with Mycobacterium
      tuberculosis protein tyrosine phosphatase MptpB.
AB  - MptpB is an essential secreted virulence factor for M. tuberculosis. Inhibition
      of MptpB impairs mycobacterial survival in host macrophages and thus helps reduce
      tuberculosis infections. However, the binding mode of the biphenyl inhibitors,
      which are known as some of the most potent MptpB inhibitors, remains unclear. In
      this study, to understand the interactions between biphenyl inhibitors and MptpB,
      docking and molecular dynamics simulations were carried out using AutoDock and
      GROMACS softwares. Calculation results show that all the biphenyl inhibitors can
      be docked to the binding site of MptpB, with the acid warheads forming a hydrogen
      bond network at the active site. But the binding modes of other terminals of
      these inhibitors are different. The cyclohexyl and trifluoromethyl substituents
      at R1 and R2 sites are necessary for the inhibitors to adopt their double-site
      binding mechanism. The estimated binding affinities are basically consistent with
      the experimental results. MD simulations show that these binding complexes
      display different stability.

PMID- 22406970
TI  - Lack of oseltamivir-resistance in A/H1N1p-infected patients, Singapore.

PMID- 22406971
TI  - Psychosocial determinants of 2009 pandemic influenza A (H1N1) vaccine
      acceptability among Indian health-care workers during the post-pandemic phase.

PMID- 22406972
TI  - A population-based case-control analysis of the association between herpes zoster
      and erectile dysfunction.
AB  - PURPOSE: To date, the occurrence of erectile dysfunction (ED) associating with
      herpes zoster (HZ) is only based on limited case reports. This case-control study
      aimed at examining the association between HZ and ED using a population-based
      dataset in Taiwan. METHODS: A total of 6429 adults newly diagnosed with ED were
      identified as cases, and 38,574 subjects without any medical history of ED were
      extracted as controls. Conditional logistic regression models were performed.
      RESULTS: In total, 1.03% out of the sampled subjects had been diagnosed with HZ
      within one year prior to the index date; a higher proportion of prior HZ was
      found among cases than controls (2.04% vs. 0.86%, p < 0.001). After adjusting for
      demographic characteristics, hypertension, diabetes, coronary heart disease,
      hyperlipidemia, obesity, and alcohol abuse/alcohol dependence syndrome,
      conditional logistic regression suggested that cases were more likely to have
      previously been diagnosed with HZ than controls (OR = 2.24, 95% CI = 1.82-2.75).
      Furthermore, the odds of having been diagnosed with an HZ infection within one
      year prior to the index date were dramatically higher among patients with ED than
      controls among subjects aged 18-29 (OR = 6.07). CONCLUSIONS: We conclude that ED
      was associated with having been previously diagnosed with HZ, particularly among
      younger males.

PMID- 22406974
TI  - The acid-mediated ring opening reactions of alpha-aryl-lactams.
AB  - 4-Aryl-azetidin-2-ones (beta-lactams) undergo ring opening with triflic acid to
      give cinnamamides which, in benzene, react further to give 3-aryl-3-phenyl
      propionamides. Prolonged reaction times in benzene give 3,3-diphenyl-propionamide
      via an aryl/phenyl exchange. Lactams of ring size 7 and higher also ring open,
      but only 7- and 8-membered rings give pure diphenylalkylamides. AlCl(3) only ring
      opens the 4-aryl-azetidinones.

PMID- 22406973
TI  - A transgenic, mesodermal specific, Dkk1 mouse model recapitulates a spectrum of
      human congenital limb reduction defects.
AB  - Congenital limb reduction defects occurring in isolation of other developmental
      abnormalities continue to be an important medical problem in which little
      progress has been made. Herein we generated transgenic mice expressing Dkk1 in an
      appendicular mesodermal pattern. Prx1-Dkk1 mice recapitulate a full spectrum of
      human congenital limb reduction defects, without other developmental issues, and
      have normal life-spans. Importantly, a close examination of the inheritance
      pattern suggests that there is a significant degree of incomplete penetrance as
      progeny of phenotypically positive or phenotypically negative, but genotypically
      positive Prx1-Dkk1 mice, consistently give rise to both phenotypically positive
      mice and phenotypically normal-appearing mice. Thus, this heterogeneous phenotype
      is reproducible with each generation regardless of the phenotype of the parents.
      We further go on to identify that mesenchymal stem cells from Prx1-Dkk1 mice have
      limited proliferative ability, but normal differentiation potential, which may
      explain the mechanism for the limb reduction defects observed. We believe Prx1
      Dkk1 mice may prove useful in the future to study the mechanisms underlying the
      development of congenital limb reduction defects.

PMID- 22406975
TI  - Distinct activation of tumor necrosis factor-alpha and interleukin-6 in the
      spinal cord after surgical incision in rats.
AB  - In a previous study, we showed that a deep thoracic incision induces the
      segmental upregulation of interleukin-1beta (IL-1beta) in the spinal cord.
      However, whether the cytokines tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) are also activated in response to surgical incision remains
      to be determined. The present study aimed to investigate the expression pattern
      of TNF-alpha and IL-6 in the spinal cord following a deep thoracic incision.
      After surgical incision, the mRNA levels of TNF-alpha and IL-6 in the thoracic
      spinal cord were transiently upregulated as determined by real-time polymerase
      chain reaction (PCR) assay. However, the activation of IL-6 was detected at 1 h
      postoperatively, which was earlier compared to that of TNF-alpha, observed at 6 h
      postoperatively. The activated TNF-alpha was mainly localized in the neurons, but
      not in microglia or astrocytes as determined by immunohistochemistry and confocal
      microscopy. However, the increased IL-6-immunoreactivity was mainly expressed in
      blood vessels. The differential upregulation of TNF-alpha and IL-6 induced by
      incision suggests that the proinflammatory cytokines may play different roles in
      the development of surgical pain.

PMID- 22406976
TI  - The effect of exchange interaction on quasiparticle Landau levels in narrow-gap
      quantum well heterostructures.
AB  - Using the 'screened' Hartree-Fock approximation based on the eight-band k.p
      Hamiltonian, we have extended our previous work (Krishtopenko et al 2011 J.
      Phys.: Condens. Matter 23 385601) on exchange enhancement of the g-factor in
      narrow-gap quantum well heterostructures by calculating the exchange
      renormalization of quasiparticle energies, the density of states at the Fermi
      level and the quasiparticle g-factor for different Landau levels overlapping. We
      demonstrate that exchange interaction yields more pronounced Zeeman splitting of
      the density of states at the Fermi level and leads to the appearance of peak
      shaped features in the dependence of the Landau level energies on the magnetic
      field at integer filling factors. We also find that the quasiparticle g-factor
      does not reach the maximum value at odd filling factors in the presence of large
      overlapping of spin-split Landau levels. We advance an argument that the behavior
      of the quasiparticle g-factor in weak magnetic fields is defined by a random
      potential of impurities in narrow-gap heterostructures.

PMID- 22406977
TI  - A pilot study investigating the effects of remote ischemic preconditioning in
      high-risk cardiac surgery using a randomised controlled double-blind protocol.
AB  - The efficacy of remote ischemic preconditioning (RIPC) in high-risk cardiac
      surgery is uncertain. In this study, 96 adults undergoing high-risk cardiac
      surgery were randomised to RIPC (3 cycles of 5 min of upper-limb ischemia induced
      by inflating a blood pressure cuff to 200 mmHg with 5 min of reperfusion) or
      control. Main endpoints were plasma high-sensitivity troponin T (hsTNT) levels at
      6 and 12 h, worst post-operative acute kidney injury (AKI) based on RIFLE
      criteria, and noradrenaline duration. hsTNT levels were log-normally distributed
      and higher with RIPC than control at 6-h post cross-clamp removal [810 ng/ml (IQR
      527-1,724) vs. 634 ng/ml (429-1,012); ratio of means 1.41 (99.17% CI 0.92-2.17);
      P=0.04] and 12 h [742 ng/ml (IQR 427-1,700) vs. 514 ng/ml (IQR 356-833); ratio of
      means 1.56 (99.17% CI 0.97-2.53); P=0.01]. After adjustment for baseline
      confounders, the ratio of means of hsTNT at 6 h was 1.23 (99.17% CI 0.88-1.72;
      P=0.10) and at 12 h was 1.30 (99.17% CI 0.92-1.84; P=0.05). In the RIPC group,
      35/48 (72.9%) had no AKI, 5/48 (10.4%) had AKI risk, and 8/48 (16.7%) had either
      renal injury or failure compared to the control group where 34/48 (70.8%) had no
      AKI, 7/48 (14.6%) had AKI risk, and 7/48 (14.6%) had renal injury or failure (Chi
      squared 0.41; two degrees of freedom; P = 0.82). RIPC increased post-operative
      duration of noradrenaline support [21 h (IQR 7-45) vs. 9 h (IQR 3-19); ratio of
      means 1.70 (99.17% CI 0.86-3.34); P=0.04]. RIPC does not reduce hsTNT, AKI, or
      ICU-support requirements in high-risk cardiac surgery.

PMID- 22406978
TI  - Acute embolization of ruptured brain arteriovenous malformations.
AB  - BACKGROUND: Ruptured brain arteriovenous malformations (bAVMs) are at increased
      risk of re-hemorrhage but management has historically been conservative. This is
      because: (1) ruptured bAVMs have not been considered as catastrophic as ruptured
      cerebral aneurysms, (2) surgical resection is aided by waiting for brain edema to
      resolve and clot to liquefy and (3) fear exists that partially treated bAVMs may
      be more dangerous than those untreated. The purpose of this study was to
      determine the feasibility and safety of acute embolization in patients with
      ruptured bAVMs. METHODS: 21 consecutive patients who underwent acute embolization
      of ruptured bAVMs from 2007 to 2011 were retrospectively reviewed. All treatments
      consisted of embolization exclusively using Onyx liquid embolic agent.
      Neurological outcomes were assessed using the Glasgow Outcome Scale (GOS) at
      hospital discharge following initial treatment. RESULTS: Nine patients (43%) were
      male, mean age was 38 years (range 8-75) and initial embolization was performed
      at a median of 4 days after ictus (mean 5.8, range 0-19). Spetzler-Martin grades
      ranged from I to VI (mean 3, median 3). In seven patients (33%) the AVM was
      completely occluded with a single treatment. With subsequent embolizations,
      complete occlusion occurred in four additional patients (19%). Six patients (29%)
      had post-embolization AVM resection and one patient (5%) had post-embolization
      gamma knife irradiation. None has suffered subsequent hemorrhages (mean follow-up
      7.5 months). The mean discharge GOS of all patients was 4.4 (range 1-5).
      CONCLUSION: Treatment of ruptured bAVMs is often delayed but our experience with
      Onyx suggests that acute embolization is safe and feasible.

PMID- 22406979
TI  - Adrenomedullin promotes human endothelial cell proliferation via HIF-1alpha.
AB  - Adrenomedullin (ADM) and hypoxia-inducible factor-1alpha (HIF-1alpha) are
      important pro-proliferation genes in response to hypoxic stress. Although it was
      reported that ADM is a target gene for HIF-1, recent studies also showed that ADM
      regulates HIF-1 expression and its activity; however, the mechanism of action
      remains unknown. Two stable human endothelial cell lines with HIF-1alpha
      knockdown by hy926-siHIF-1alpha or HMEC-siHIF-1alpha were established. mRNA and
      protein expression of ADM and HIF-1alpha in EA.hy926 and HMEC1 cells were
      examined under hypoxic stress. Upon ADM treatment, cell proliferation was
      investigated and the expression profiles of HIF-1alpha and its target genes
      (VEGF, PFKP, PGK1, and AK1) were examined. Furthermore, the proline hydroxylase
      (PHD) mRNA level and its activity were investigated. We observed that mRNA and
      protein expression of ADM in hypoxia are earlier events than HIF-1alpha in
      EA.hy926 and HMEC1 cells. ADM-promoted cell proliferation of endothelial cells,
      which was HIF-1alpha dependent. We also found that ADM up-regulated the mRNA and
      protein expressions of HIF-1alpha- and HIF-1-targeted genes, and ADM up-regulated
      the protein expressions of HIF-1alpha through down-regulation of PHD mRNA
      expression and PHD activity.

PMID- 22406980
TI  - Identification of a major QTL for silique length and seed weight in oilseed rape
      (Brassica napus L.).
AB  - Silique length (SL) and seed weight (SW) are two important yield-related traits
      controlled by quantitative trait loci (QTL) in oilseed rape (Brassica napus L.).
      The genetic bases underlying these two traits are largely unknown at present. In
      this study, we conducted QTL analyses for SL and SW using 186 recombinant inbred
      lines (RILs) derived from a cross between S1, an EMS mutant with extremely long
      siliques and large seeds, and S2, an inbred line with regular silique length and
      seed size. RILs were grown in Wuhan in the 2008/09 (SS09) and 2009/10 (SS10)
      growing seasons, and mean SL and SW for each line were investigated. Ten non
      redundant QTL were identified for SL. Of these, a major QTL, cqSLA9, consistently
      explained as much as 53.4% of SL variation across environments. The others are
      minor QTL and individually explained less than 10% of the SL variation. Nine non
      redundant QTL were identified for SW. Of which, one major QTL, cqSWA9, explained
      as much as 28.2% of the total SW variation in the SS09 and SS10 environments. In
      addition, three additive by additive interactions with small effects were
      detected for SL, and no interactions were detected for SW. Interestingly, the two
      major QTL, cqSLA9 for SL and cqSWA9 for SW colocalized in the same chromosomal
      region and were integrated into a unique QTL, uqA9. The S1 allele at this locus
      increases both SL and SW, suggesting that uqA9 has pleiotropic effects on both SL
      and SW. The existence and effect of uqA9 was confirmed in genetically different
      RILs derived from the cross between S1 and No2127, a resynthesized DH line having
      regular silique length and seed size. Individuals in one residual heterozygous
      line for cqSLA9 showed significant difference in silique length. The results in
      this study revealed that silique length in the S1 mutant is mainly controlled by
      the cqSLA9 locus, which will be suitable for fine mapping and marker-assisted
      selection in rapeseed breeding for high yield.

PMID- 22406981
TI  - Mapping QTL for resistance to eyespot of wheat in Aegilops longissima.
AB  - Eyespot is an economically important disease of wheat caused by the soilborne
      fungi Oculimacula yallundae and O. acuformis. These pathogens infect and colonize
      the stem base, which results in lodging of diseased plants and reduced grain
      yield. Disease resistant cultivars are the most desirable control method, but
      resistance genes are limited in the wheat gene pool. Some accessions of the wheat
      wild relative Aegilops longissima are resistant to eyespot, but nothing is known
      about the genetic control of resistance. A recombinant inbred line population was
      developed from the cross PI 542196 (R) * PI 330486 (S) to map the resistance
      genes and better understand resistance in Ae. longissima. A genetic linkage map
      of the S(l) genome was constructed with 169 wheat microsatellite markers covering
      1261.3 cM in 7 groups. F(5) lines (189) were tested for reaction to O. yallundae
      and four QTL were detected in chromosomes 1S(l), 3S(l), 5S(l), and 7S(l). These
      QTL explained 44 % of the total phenotypic variation in reaction to eyespot based
      on GUS scores and 63 % for visual disease ratings. These results demonstrate that
      genetic control of O. yallundae resistance in Ae. longissima is polygenic. This
      is the first report of multiple QTL conferring resistance to eyespot in Ae.
      longissima. Markers cfd6, wmc597, wmc415, and cfd2 are tightly linked to
      Q.Pch.wsu-1S ( l ), Q.Pch.wsu-3S ( l ), Q.Pch.wsu-5S ( l ), and Q.Pch.wsu-7S ( l
      ), respectively. These markers may be useful in marker-assisted selection for
      transferring resistance genes to wheat to increase the effectiveness of
      resistance and broaden the genetic diversity of eyespot resistance.

PMID- 22406982
TI  - Expression of CD40 and growth-inhibitory activity of CD40 agonist in ovarian
      carcinoma cells.
AB  - The CD40 receptor is a member of the tumour necrosis factor receptor family and
      is widely expressed on various cell types. The antitumour activity of CD40
      agonist antibody has been observed in B-cell-derived malignancies, but its
      activity on ovarian cancer remains unclear. However, in this paper, we first
      confirmed that the anti-CD40 agonist antibody could inhibit the growth of ovarian
      cancer cells and induce apoptosis. This study investigated the expression of CD40
      by ovarian carcinoma tissues and cell lines, at the same time, we evaluated the
      effect of a recombinant soluble human CD40L (rshCD40L) and an anti-CD40 agonist
      antibody on cell growth and apoptosis. Flow cytometry and immunohistochemistry
      assay demonstrated that CD40 was expressed on ovarian carcinoma cell lines and
      primary ovarian carcinoma cells derived from ascites, as well as on ovarian
      carcinoma tissues. The growth inhibition of rshCD40L and the anti-CD40 agonist
      antibody on ovarian carcinoma cells was examined by MTT assay, and the proportion
      of apoptotic tumour cells was analysed by flow cytometry and Hoechst staining.
      Our study showed that CD40 was expressed on all ovarian carcinoma cell lines and
      was examined in 86.2% (162/188) of ovarian cancer tissue samples, but not in
      normal ovarian tissues (n = 20). Treatment with rshCD40L or anti-CD40 agonist
      antibody significantly inhibited ovarian carcinoma cell growth and induced
      apoptosis. Theses results suggest that CD40 is expressed on ovarian carcinoma
      cells, moreover, that rshCD40L and anti-CD40 agonist antibody have therapeutic
      potential to inhibit human ovarian cancer growth.

PMID- 22406983
TI  - Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function
      and promotes anti-tumor activity.
AB  - 4-1BB (CD137, TNFRSF9) is a costimulatory receptor expressed on several subsets
      of activated immune cells. Numerous studies of mouse and human T cells indicate
      that 4-1BB promotes cellular proliferation, survival, and cytokine production. 4
      1BB agonist mAbs have demonstrated efficacy in prophylactic and therapeutic
      settings in both monotherapy and combination therapy tumor models and have
      established durable anti-tumor protective T-cell memory responses. PF-05082566 is
      a fully human IgG2 that binds to the extracellular domain of human 4-1BB with
      high affinity and specificity. In preclinical studies, this agonist antibody
      demonstrated its ability to activate NF-kappaB and induce downstream cytokine
      production, promote leukocyte proliferation, and inhibit tumor growth in a human
      PBMC xenograft tumor model. The mechanism of action and robust anti-tumor
      efficacy of PF-05082566 support its clinical development for the treatment of a
      broad spectrum of human malignancies.

PMID- 22406984
TI  - Pain management in victims of conflict.
AB  - PURPOSE OF REVIEW: The purpose of this review is to look at the options available
      for the management of pain in victims of conflict, from the point of wounding,
      through a chain of evacuation, to rehabilitation in the home country. This is
      relevant for all healthcare workers as any could find themselves treating
      veterans and having a clear understanding of what occurred will help. RECENT
      FINDINGS: The article will discuss developments in the prehospital environment,
      the field hospital, during repatriation and back in the home country to include
      neurostimulation in cases of refractory pain. Evidence when available is provided
      and the difficulties in conducting research in this environment are touched upon.
      SUMMARY: The current agents, routes and techniques found in any civilian medical
      service can be brought to bear with great benefit. However, the secret appears to
      lie in a robust approach to the importance of treating pain, encouraged in all
      healthcare professionals, and the recognition of the role of integrating the
      healthcare package throughout the chain of evacuation. Research remains
      difficult.

PMID- 22406985
TI  - Acute pain management in patients with persistent pain.
AB  - PURPOSE OF REVIEW: Over the past 20 years, prescriptions of opioids for chronic
      pain have increased dramatically. This review addresses the difficulties in
      managing acute pain in this growing group of patients and discusses evidence
      relating to opioid tolerance and hyperalgesia and new avenues of research in
      specific painful conditions. RECENT FINDINGS: There is accumulating evidence
      surrounding the dangers of high-dose opioids and the risk of overdose and death.
      Employing nonopioid analgesics and disease-modifying drugs to cover an acute
      exacerbation of pain will thus limit escalating opioid doses. In specific
      diseases, the role of oxidative stress and the disruption of calcium homeostasis
      may provide treatment targets in acute pancreatitis; the identification of
      psychological stressors may decrease the frequency of acute exacerbations of
      abdominal pain; modifying the adhesion of sickle cells to inflamed endothelium
      may reduce vaso-occlusive crises; while vertebroplasty and calcitonin appear to
      improve pain and functioning after osteoporotic vertebral fractures. SUMMARY:
      Much of the evidence regarding the acute pain management of chronic pain patients
      is extrapolated from studies of opioid-naive patients undergoing surgery. More
      focused research is needed to ascertain whether this model is an appropriate one
      to follow for such a complex group of patients.

PMID- 22406986
TI  - Medically unexplained symptoms and pain:  misunderstanding and myth.
AB  - PURPOSE OF REVIEW: The recent resurgence of the notion of psychosomatic
      disorders, grouping together as 'medically unexplained symptoms' all those
      without organic diagnosis and associated with distress, has included all chronic
      (persistent) pain within its remit. As pain is reasonably well explained, within
      an integrated biopsychosocial model, critical analysis of the position is
      required. RECENT FINDINGS: Neuroscientific and translational studies of pain
      mechanisms have strengthened the understanding of pain, providing stronger
      connections between abstract psychological concepts corresponding to observation
      and studies of human clinical populations, neuroscientific findings in clinical
      and analogue studies, and animal research. This situation is contrasted with even
      the most recent reviews of medically unexplained symptoms providing only vague
      and patchily supported mechanisms, with little cognate human analogue or animal
      research. SUMMARY: The implication of subsuming chronic pain under medically
      unexplained symptoms is that the primary care/community physician will try to
      persuade the patient that the symptoms indicate underlying depression, which her
      or she may offer to treat. When pain is instead recognized as a problem in its
      own right, it would be referred for specialist opinion and care, or treated
      directly with evidence-based pain interventions.

PMID- 22406987
TI  - Management of acute and chronic migraine.
AB  - PURPOSE OF REVIEW: We highlight the recent clinical trials for the management of
      acute and chronic migraine. RECENT FINDINGS: In women with menstrual migraine,
      triptans seem to be well tolerated irrespective of whether or not patients are
      taking oestrogen-containing contraceptives or have comorbidities that indicate
      increased cardiovascular risk. The new acute drug, telcagepant, a calcitonin gene
      related peptide (CGRP) antagonist, is safe for long-term use (up to 18 months) in
      migraine patients with stable coronary artery disease in whom the use of triptans
      is not advisable. From the pooled analysis of the two Phase III Research
      Evaluating Migraine Prophylaxis Therapy studies of onabotulinumtoxinA (BOTOX) in
      chronic migraineurs, it clearly emerged that efficacy increases overtime (up to
      56 weeks) and paralleled self-perceived improvement in quality of life.
      Effectiveness was also observed in patients with severely disabling headaches,
      who met criteria for triptan abuse and were refractory to several prophylactic
      treatments. Finally, combination of preventive pharmacological agents with
      different action mechanisms may be the next frontier in therapeutic advancements
      for treating migraine. SUMMARY: Although triptans are safe and well tolerated,
      CGRP antagonists may be an option for nonresponsive patients or those in whom the
      use of triptans is not advisable. New drugs and combinations of old therapeutic
      options may help patients with severe forms of headache.

PMID- 22406988
TI  - 41.5-kDa Cathepsin L protease from Clonorchis sinensis: expression,
      characterization, and serological reactivity of one excretory-secretory antigen.
AB  - Cysteine proteases (CPs) were associated with the pathogenicity and excystment of
      Clonorchis sinensis. Most of them were potential antigens for the immunodiagnosis
      of clonorchiasis. More researches on CPs will let us know more about their
      functions, and further employ them for the development of more efficient
      diagnostic reagent and prevention strategies. In the current study, a full-length
      sequence encoding cathepsin L from C. sinensis (CsCL41.5) was identified from our
      adult cDNA library. Bioinformatic analysis showed that CsCL41.5 included typical
      motifs of cathepsin L (ERFNIN and GNFD motifs) and conserved amino acid positions
      which constituted the active center of the enzyme. The identity of its amino acid
      sequence with the cathepsin L of Schistosoma japonicum was 49.6 %. Recombinant
      CsCL41.5 (rCsCL41.5) was highly expressed in the form of inclusion body in
      Escherichia coli, and soluble rCsCL41.5 was obtained after purification and
      renaturation. Western blotting analysis indicated that CsCL41.5 is an excretory
      secretory antigen of C. sinensis adult. Immunolocalization demonstrated that
      CsCL41.5 is distributed in the intestine and eggs in the uterus of adult worm,
      tegument of metacercaria, oral suck, and tail of cercaria. ELISA assays showed
      that IgG4 was the predominant IgG isotype responding to rCsCL41.5 in sera from
      clonorchiasis patients. The sensitivity and specificity of specific IgG4
      detection with rCsCL41.5 was 62.5 % (15/24) and 81.7 % (49/60), respectively. It
      was concluded that there were differences in biological function, efficiency of
      serodiagnosis, and characterization of immune reactivity between CsCL41.5 and
      other CPs of C. sinensis, combining with previous studies.

PMID- 22406989
TI  - Prevalence of visceral obesity estimated by predictive equation in young women
      from Pernambuco.
AB  - BACKGROUND: The accumulation of visceral fat is considered a major risk factor
      for cardiovascular and metabolic diseases. OBJECTIVE: To determine the prevalence
      of visceral obesity and to assess its association with cardiovascular risk
      factors in young women from the state of Pernambuco. METHODS: Cross-sectional
      study carried out with data from the "III Health and Nutrition State Survey",
      involving women aged 25 to 36 years. The following variables were evaluated: body
      mass index (BMI), Waist Circumference (WC), waist-to-height ratio (WHtR), volume
      of visceral fat (VVF) estimated by a predictive equation, Systolic and Diastolic
      Blood Pressure (SBP, DBP), total cholesterol (TC), Triglycerides (TG), fasting
      glucose (FG). RESULTS: A total of 517 women were evaluated, with a median age of
      29 years (27-32) and prevalence of visceral obesity of 30.6%. BMI, SBP, DBP and
      TG were higher in the group with visceral obesity: BMI = 28.0 kg/m2 (25.0 to
      21.4) vs. 23.9 kg/m2 (21.5 to 26.4) , SBP = 120.0 mmHg (110.0 to 130.0) vs. 112.0
      mmHg (100.0 to 122.0), DBP = 74 mmHg (70-80) vs. 70 mmHg (63-80); TG = 156.0 mg /
      dL (115.0 to 203.2) vs. 131.0 mg / dL (104.0 to 161.0), respectively, p < 0.01.
      Age, SBP, DBP, TG and TC levels were significantly and positively correlated with
      the VVF: r = 0.171, 0.224, 0.163, 0.278, 0.124 respectively, p < 0.005.
      CONCLUSION: A high prevalence of visceral obesity was observed, being
      statistically correlated with cardiovascular risk factors.

PMID- 22406990
TI  - Impact of stenting and oral sirolimus on endothelium-dependent and independent
      coronary vasomotion.
AB  - BACKGROUND: There is no consensus regarding the impact of stenting on long-term
      endothelial function. There have been reports of increased endothelial
      dysfunction with sirolimus-eluting stents as compared to bare metal stenting
      (BMS). OBJECTIVE: This study aims to assess the impact of BMS and the effect of
      oral sirolimus on endothelial function. METHODS: Forty-five patients were
      randomized into three groups: BMS + high-dose oral sirolimus (initial dose of 15
      mg, followed by 6 mg/day for four weeks); BMS + low-dose sirolimus (6 mg followed
      by 2 mg daily for four weeks); and BMS without sirolimus. Changes in
      vasoconstriction or vasodilation in a 15 mm segment starting at the distal stent
      end in response to acetylcholine and nitroglycerin were assessed by quantitative
      angiography. RESULTS: The groups had similar angiographic characteristics. The
      percent variation in diameter in response to acetylcholine was similar in all
      groups at the two time points (p = 0.469). Four hours after stenting, the target
      segment presented an endothelial dysfunction that was maintained after eight
      months in all groups. In all groups, endothelium-independent vasomotion in
      response to nitroglycerin was similar at four hours and eight months, with
      increased target segment diameter after nitroglycerin infusion (p = 0.001).
      CONCLUSION: The endothelial dysfunction was similarly present at the 15 mm
      segment distal to the treated segment, at 4 hours and 8 months after stenting.
      Sirolimus administered orally during 4 weeks to prevent restenosis did not affect
      the status of endothelium-dependent and independent vasomotion.

PMID- 22406991
TI  - Heart rate variability in myotonic dystrophy type 1 patients.
AB  - BACKGROUND: Cardiac involvement is common in myotonic dystrophy (MD) patients.
      Heart rate variability (HRV) is a simple and reliable technique that can be
      useful for studying the influence of the autonomic nervous system on the heart.
      OBJECTIVE: Study heart rate variability in patients with type 1 MD. METHODS: We
      studied HRV during 5-minute recordings in MD patients and in a healthy control
      group. We analyzed frequency domains (LF and HF) in normalized units (nu) and
      sympathovagal balance, in the sitting and supine position. RESULTS: Seventeen
      patients (10 men and 7 women) and seventeen matched healthy individuals (10 men
      and 7 women) were studied. Sympathetic and parasympathetic modulations of the
      heart increased in male MD patients from supine to sitting position in 19% of
      LFnu and the LF/HF ratio rose by 42.3%. In the sitting position, male MD patients
      exhibited significantly higher sympathovagal balances in 50.9% compared to
      healthy control individuals. HRV was influenced by both gender and disease.
      Gender influenced LFnu in the supine position while the LF/HF ratio and HFnu were
      affected in both positions. Post hoc analyses showed that gender significantly
      impacts MD patients and healthy individuals in different ways (p < 0.01). The low
      frequency domain in the sitting position (LFnu) was significantly influenced by
      the disease. CONCLUSION: The results of this study suggest that the sympathetic
      drive in middle-aged male MD patients who are not severely impaired and present
      moderate disease duration seems to be greater than in healthy matched
      individuals.

PMID- 22406992
TI  - Sorafenib and HDAC inhibitors synergize to kill CNS tumor cells.
AB  - The present studies were designed to determine whether the multi-kinase inhibitor
      sorafenib (Nexavar) interacted with histone deacetylase inhibitors to kill
      glioblastoma and medulloblastoma cells. In a dose-dependent fashion sorafenib
      lethality was enhanced in multiple genetically disparate primary human
      glioblastoma isolates by the HDAC inhibitor sodium valproate (Depakote). Drug
      exposure reduced phosphorylation of p70 S6K and of mTOR. Similar data to that
      with valproate were also obtained using the HDAC inhibitor vorinostat (Zolinza).
      Sorafenib and valproate also interacted to kill medulloblastoma and PNET cell
      lines. Treatment with sorafenib and HDAC inhibitors radio-sensitized both GBM and
      medulloblastoma cell lines. Knock down of death receptor (CD95) expression
      protected GBM cells from the drug combination, as did overexpression of c-FLIP-s,
      BCL-XL and dominant negative caspase 9. Knock down of PDGFRalpha recapitulated
      the effect of sorafenib in combination with HDAC inhibitors. Collectively, our
      data demonstrate that the combination of sorafenib and HDAC inhibitors kills
      through activation of the extrinsic pathway, and could represent a useful
      approach to treat CNS-derived tumors.

PMID- 22406993
TI  - Antitumor effects of novel shorter truncated insulin-like growth factor I
      receptors.
AB  - We generated novel truncated insulin-like growth factor I receptors (IGF-IRs)
      designated as 126/STOP, 223/STOP and 325/STOP in order to establish shorter
      soluble IGF-IRs than previously reported 486/STOP without abrogating the same
      antitumor effects. Stable transfection of 223/STOP and 325/STOP, but not 126/STOP
      caused inhibition of anchorage-independent growth of CaOV-3 ovarian cancer cells
      in vitro. This antitumor effect was reproduced when we used recombinant proteins
      of these constructs, suggesting a bystander effect of these shorter truncated IGF
      IRs. Tumorigenesis in vivo of CaOV-3 cells tranfected with 223/STOP or 325/STOP
      was strictly inhibited, and inoculation of these cells in nude mice caused
      massive apoptosis exclusively in vivo. Phosphorylations of IGF-IR and Akt, but
      not Erk were attenuated in 223/STOP- or 325/STOP-transfected CaOV-3 cells, and
      downregulations of IGF-IR and Akt phosphorylation seemed to play at least a
      partial role in the anti-tumor effect of these novel truncated IGF-IRs. Since
      223/STOP and 325/STOP are smaller in size than previously reported 486/STOP, and
      they retain the same antitumor effects, they could be good candidates for
      clinical application in the future.

PMID- 22406994
TI  - Serum calcium, tumor size, and hormone receptor status in women with untreated
      breast cancer.
AB  - Elevated serum levels of calcium are frequently observed in advanced breast
      cancer, but data on serum calcium and breast cancer characteristics at the time
      of breast cancer diagnosis are limited. We conducted a cross-sectional study of
      555 women with newly-diagnosed, untreated breast cancer in North Dakota. We
      examined the relationship between tumor size, serum calcium and other clinical
      characteristics of breast tumors, including age and hormone receptor status,
      using multiple linear regressions. Tumors that were estrogen receptor negative
      tended to be associated with higher serum calcium levels (p = 0.07). We observed
      a significant positive correlation between tumor volume and serum calcium levels
      (adjusted for patient age, body mass index, hormonal receptors, stage at
      diagnosis, and grade). The association between tumor volume and serum calcium was
      limited to post-menopausal women. Our finding that postmenopausal women with
      larger breast tumors had significantly higher serum calcium levels is consistent
      with a calciotropic effect of early breast cancer in postmenopausal women.

PMID- 22406995
TI  - Sorafenib inhibits endogenous and IL-6/S1P induced JAK2-STAT3 signaling in human
      neuroblastoma, associated with growth suppression and apoptosis.
AB  - Neuroblastoma is the most common extracranial solid tumor in the pediatric
      population. Sorafenib (Nexavar), a multikinase inhibitor, blocks cell
      proliferation and induces apoptosis in certain types of cancers. Here, we tested
      antitumor effects of sorafenib (<= 10 uM) on four human neuroblastoma cell lines,
      CHLA255, CHLA171, CHLA90 and SK-N-AS. Sorafenib inhibited cell proliferation and
      induced apoptosis of neuroblastoma tumor cells in a dose-dependent manner.
      Sorafenib inhibited phosphorylation of Signal Transducer and Activator of
      Transcription 3 (STAT3) proteins at Tyr705 in these cells, associated with
      inhibition of phosphorylated JAK2, an upstream kinase that mediates STAT3
      phosphorylation. Expression of a constitutively-activated STAT3 mutant (pSTAT3-C)
      partially blocked the antitumor effects of sorafenib on neuroblastoma cells.
      Sorafenib also inhibited the phosphorylation of STAT3 induced by IL-6 and
      sphingosine-1-phosphate (S1P), a recently identified regulator for STAT3, in
      these tumor cells. Moreover, sorafenib downregulated phosphorylation of MAPK
      (p44/42) in neuroblastoma cells, consistent with inhibition of their upstream
      regulators MEK1/2. Sorafenib inhibited expression of cyclin E, cyclin D1/D2/D3,
      key regulators for cell cycle, and the antiapoptotic proteins Mcl-1 and survivin.
      Finally, sorafenib suppressed the growth of human neuroblastoma cells in a mouse
      xenograft model. Taken together, these findings suggest the potential use of
      sorafenib for the treatment of pediatric neuroblastomas.

PMID- 22406996
TI  - Resveratrol sensitized leukemia stem cell-like KG-1a cells to cytokine-induced
      killer cells-mediated cytolysis through NKG2D ligands and TRAIL receptors.
AB  - Human promyeloblastic leukemia KG-1a cells exhibit many characteristics similar
      to leukemia stem cells, which are resistant to chemotherapeutic drugs and
      hyposensitive to cytotoxic cells. Resveratrol (RES), as a member of plant
      polyphenols, has gained considerable attention due to its ability to prevent
      cancer from progressing. In this study, the potential of RES to sensitize KG-1a
      cells to cytolysis of cytokine-induced killer cells (CIKs) through NKG2D ligands
      and TNF-related apoptosis-inducing ligand (TRAIL) receptors were investigated.
      Twenty-five micromolars RES was found to inhibit approximately 50% of KG-1a cell
      growth and had the least growth-inhibition effect on peripheral blood mononuclear
      cells (PBMCs) after 24 h. Utilizing cytokines including interleukin-2 (IL-2) and
      interleukin-15 (IL-15) to activate PBMCs, we obtained substantial CD3 (+) CD56
      (+) natural killer cell-like T lymphocytes that secreted cytokine interferon
      gamma (IFN-gamma) and expressed NKG2D and TRAIL on their surfaces (i.e., cytokine
      induced killer cells, CIKs). RES was shown to render KG-1a cells susceptible to
      CIK-mediated cytolysis estimated by LDH-release assay. This heightened
      sensitivity correlated with an increase in cell-surface expression of NKG2D
      ligands and death receptor 4 (DR4), coupled with a downregulation of cell-surface
      expression of decoy receptor 1 (DcR1) in KG-1a cells. Blocking NKG2D ligands or
      TRAIL with monoclonal antibodies could abrogate CIKs-mediated cytolysis. These
      results demonstrated that increased sensitivity of KG-1a cells, modulated by RES
      to alloreactive CIKs-mediated cytolysis is a phenomenon attributable to induced
      expression of NKG2D ligands and activation of TRAIL pathway. Thus, resveratrol
      combined with alloreactive CIKs merits clinical evaluation as a novel and
      effective immunotherapy strategy to eliminate residual leukemia stem cells.

PMID- 22406997
TI  - Sensitization of (colon) cancer cells to death receptor related therapies: a
      report from the FP6-ONCODEATH research consortium.
AB  - The objective of the ONCODEATH consortium [EU Research Consortium "ONCODEATH"
      (2006-2010)] was to achieve sensitization of solid tumor cells to death receptor
      related therapies using rational mechanism-based drug combinations of targeted
      therapies. In this collaborative effort, during a period of 42 mo, cell and
      animal model systems of defined oncogenes were generated. Exploitation of
      generated knowledge and tools enabled the consortium to achieve the following
      research objectives: (1) elucidation of tumor components which confer sensitivity
      or resistance to TRAIL-induced cell death; (2) providing detailed knowledge on
      how small molecule Hsp90, Aurora, Choline kinase, BRAF inhibitors, DNA damaging
      agents, HDAC and DNMT inhibitors affect the intrinsic apoptotic amplification and
      execution machineries; (3) optimization of combined action of TRAIL with these
      therapeutics for optimum effects with minimum concentrations and toxicity in
      vivo. These findings provide mechanistic basis for a pharmacogenomic approach,
      which could be exploited further therapeutically, in order to reach novel
      personalized therapies for cancer patients.

PMID- 22406998
TI  - Ginsenoside Rg3 attenuates tumor angiogenesis via inhibiting bioactivities of
      endothelial progenitor cells.
AB  - Accumulating evidence suggests that Ginsenoside Rg3 appears to inhibit tumor
      growth including Lewis lung carcinoma, intestinal adenocarcinomas or B16 melanoma
      by inhibiting cell proliferation, tumor cell invasion and metastasis. Endothelial
      progenitor cells (EPCs) appear to play a key role in the growth of early tumors
      by intervening with the angiogenic switch promoting tumor neovessel formation by
      producing angiogenic cytokines during tumor progression. This paper reports a
      novel mechanism of Ginsenoside Rg3, a candidate anticancer bio-molecule, on tumor
      angiogenesis by inhibiting the multiple bioactivities of EPCs. When Ginsenoside
      Rg3 was applied to the ex vivo cultured outgrowth ECs, a type of EPCs, it
      inhibited the cell proliferation, cell migration and tubular formation of EPCs.
      Importantly, Ginsenoside Rg3 attenuated the phosphorylation cascade of the VEGF
      dependent p38/ERK signaling in vitro. The xenograft tumor model clearly showed
      that Ginsenoside Rg3 suppresses tumor growth and tumor angiogenesis by inhibiting
      the mobilization of EPCs from the bone marrow microenvironment to the peripheral
      circulation and modulates VEGF-dependent tumor angiogenesis. In conclusion, this
      study provides a potential therapeutic molecule, Ginsenoside Rg3, as an
      anticancer drug by inhibiting the EPC bioactivities.

PMID- 22406999
TI  - Hedgehog signaling in glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is the most malignant brain tumor in adults with a
      median survival of 14.6 mo under the best available treatment. New treatment
      strategies are therefore urgently required, for which a profound understanding of
      tumor biology is necessary. Much effort has been devoted to tumor-specific
      aberrant signaling processes. Recently it was discovered that the transcription
      factor Gli1, which is activated by hedgehog signaling, is a highly predictive
      marker in GBM, as determined by immunohistochemistry. To determine whether GBM
      cells have transcriptionally active Gli1, we performed experiments with reporter
      genes with cells isolated from surgically removed human tumors and cell lines. We
      also determined whether the hedgehog signaling inhibitor cyclopamine influences
      reporter gene expression and cell viability, and we determined the expression of
      Gli1, SHH and Patched1 by quantitative real-time RT-PCR. Reporter gene analysis
      of nine cultures and four cell lines demonstrated a significantly enhanced
      transcriptional activity in six tumor cell cultures and all cell lines. Analysis
      of cell viability in the presence of cyclopamine revealed a response of all cell
      cultures with the exception of one primary culture and one cell line, but only
      one cell line responded to cyclopamine with reduced hedgehog signaling activity.
      This indicates that the toxicity of cyclopamine toward GBM cells is independent
      from hedgehog signaling. Since no correlation between hedgehog activity and SHH,
      Gli1 and Patched1 mRNA levels was observed we conclude that other mechanisms
      aside from transcriptional regulation of these factors are responsible for
      hedgehog activity in tumor cells derived from GBM.

PMID- 22407000
TI  - Investigation on synthesis and properties of isosorbide based bis-GMA analogue.
AB  - The aim of this work was to synthesize and investigate properties of a novel
      dimethacrylic monomer based on bioderived alicyclic diol--isosorbide. Its
      potential as a possible substitute of 2,2-bis[4-(2-hydroxy-3
      methacryloyloxypropoxy)phenyl]propane (BISGMA), widely used in dental restorative
      materials and suspected for toxicity was assessed. The novel monomer was obtained
      in a three-step synthesis. First, isosorbide was etherified by a Williamson
      nucleophilic substitution and subsequently oxidized to isosorbide diglycidyl
      ether (ISDGE). A triphenyl phosphine catalyzed addition of methacrylic acid to
      ISDGE resulted in 2,5-bis(2-hydroxy-3-methacryloyloxypropoxy)- 1,4:3,6-dianhydro
      sorbitol (ISDGMA). The monomer obtained was photopolymerized using
      camphorquinone/2-(dimethylamino)ethyl methacrylate initiating system. Next,
      compositions with triethylene glycol dimethacrylate (TEGDMA) were prepared and
      polymerized. Double bond conversion, polymerization shrinkage and water sorption
      of resulting polymers were determined. Selected mechanical (flexular strength and
      modulus, Brinell hardness) and thermomechanical (DMA analysis) properties were
      also investigated. BISGMA based materials were prepared as reference for
      comparison of particular properties.

PMID- 22407001
TI  - Effect of protein concentrations of bovine serum albumin and gamma-globulin on
      the frictional response of a cobalt-chromium femoral head.
AB  - The study aims to identify the concentration-dependent role of bovine serum
      albumin (BSA) and gamma-globulin in the lubricating ability of a cobalt-chromium
      femoral head. The frictional coefficients of the cobalt-chromium femoral head
      decreased with increasing BSA concentrations from 10 to 40 mg/ml and showed
      statistical differences between any of the BSA concentration groups, except
      between the 30 and 40 mg/ml concentration groups. In gamma-globulin, the
      frictional coefficients significantly decreased at concentrations of 2.5 and 5.0
      mg/ml as compared with the PBS control group, but significant increases were
      observed at 7.5 and 12.5 mg/ml. These results suggest that the friction of the
      cobalt-chromium femoral head is dependent on the concentration of both BSA and
      gamma-globulin. However, there is a maximum concentration for BSA to act as an
      effective boundary lubricant, while the lubricating ability of gamma-globulin is
      most effective in the physiological concentration range within human synovial
      fluid.

PMID- 22407002
TI  - Antimicrobial effects of nanofiber poly(caprolactone) tissue scaffolds releasing
      rifampicin.
AB  - This study quantified the antibiotic release kinetics and subsequent bactericidal
      efficacy of rifampicin (RIF) against Gram-positive and Gram-negative bacteria
      under in vitro static conditions. Antibiotic-loaded scaffolds were fabricated by
      electrospinning poly(caprolactone) (PCL) with 10% or 20% (w/w) RIF. Scaffold
      fiber diameter and RIF loading were characterized, and RIF release kinetics were
      measured. RIF-releasing and RIF-free scaffolds were inoculated with Pseudomonas
      aeruginosa and Staphylococcus epidermidis, and the suspended concentration live
      and dead bacteria were determined by fluorescent microscopy. Adherent bacteria
      and biofilm formation were examined using scanning electron microscopy. Mean
      fiber diameters were 557 +/- 399 nm for RIF-free, 402 +/- 225 nm for 10% RIF, and
      665 +/- 402 nm for 20% RIF scaffolds. RIF release kinetics exhibited a short
      burst release during the first hour, followed by a 7 h, zero-order release during
      which both RIF scaffolds released ~50% of their initial RIF mass loading. P.
      aeruginosa and S. epidermidis suspended cell populations proliferated in
      accordance with logarithmic growth models when exposed to control scaffolds;
      however both RIF-containing scaffolds completely inhibited bacterial growth in
      suspension and, subsequently, prevented biofilm formation within the scaffolds
      through the first 6 h.

PMID- 22407003
TI  - Tacrolimus 0.1% vs mometasone furoate topical treatment in allergic contact hand
      eczema: a prospective randomized clinical study.
AB  - Tacrolimus is a macrolide immunosuppressant that has been demonstrated to inhibit
      T-lymphocyte activation without the side-effects of corticosteroids. The safety
      profile of tacrolimus makes it a promising therapeutic option for dermatitis. To
      evaluate and compare the therapeutic ability of tacrolimus 0.1% ointment and
      mometasone furoate 0.1% ointment in patients with chronic hand eczema and
      positive patch tests. Thirty adults with chronic hand eczema and positive patch
      test reaction to relevant contact allergens were treated with tacrolimus 0.1%
      ointment or mometasone furoate 0.1% ointment in a single-centre, randomized
      comparative study. The scores of the evaluated clinical parameters (erythema,
      infiltration, vesiculation, desquamation, presence of cracks and itching) did not
      differ between Groups A and B at any of the four time points (p>0.05).On the
      other hand, in both groups, a significant difference was detected in all
      parameters between baseline and Day 90 recorded values. Tacrolimus is a promising
      alternative therapy for contact dermatitis patients as it is effective from the
      first month of treatment, well tolerated and offers similar therapeutic results
      to topical corticosteroid therapy.

PMID- 22407004
TI  - Study of c-kit immunoexpression in canine cutaneous melanocytic tumors.
AB  - Melanocytic tumors occur as much in humans as in dogs and are frequently
      associated with receptor tyrosine kinase dysregulation. The transmembrane c-kit
      protein is a receptor tyrosine kinase that is crucial in melanocytic homeostasis
      and, when mutated, is associated with tumor development in those cells. In human
      studies, its expression is generally detected in melanocytomas and primary
      malignant melanomas, being lost with tumor progression and metastasis. In this
      study, we aimed to analyze c-kit expression in canine cutaneous melanocytic
      tumors and its association with tumor behavior, in order to investigate the dog's
      potential in comparative pathology and c-kit's potential in the diagnosis of
      these tumors. The expression of c-kit was evaluated immunohistochemically in 39
      canine cutaneous melanocytic tumors and scored in terms of the labeling location,
      extension, and intensity. The labeling location was essentially cytoplasmic, and
      the labeling extension and intensity were generally higher in melanocytomas
      (83.3% diffuse-labeled cells) than those in malignant melanomas (22.2% negative
      labeled cells). The differences found in the labeling extension were
      statistically significant (P < 0.001). There was no association between c-kit
      immunoexpression in malignant melanomas and the clinicopathological criteria,
      except between the labeling intensity and the degree of intralesional
      pigmentation (P = 0.048). Our results for labeling extension are in agreement
      with similar human studies, reinforcing the dog's potential as a model organism
      for investigation in this type of cancer. In addition, the loss of c-kit
      expression in malignant melanomas might be a criterion of tumor aggressiveness,
      indicating that this receptor may be useful in the diagnosis of these tumors.

PMID- 22407005
TI  - Gradient HPLC-DAD stability indicating determination of miconazole nitrate and
      lidocaine hydrochloride in their combined oral gel dosage form.
AB  - The pharmaceutical combination of miconazole nitrate (MZ) and lidocaine
      hydrochloride (LD) is used in the curative and prophylactic therapy of the oral
      and gastro-intestinal infections caused by Candida albicans. To the best of our
      knowledge, no attempts have yet been made to assay this combination by any
      analytical method. A simple and selective high-performance liquid chromatography
      diode array detection (HPLC-DAD) stability-indicating method was developed for
      the simultaneous determination of MZ and LD in their combined formulation.
      Effective chromatographic separation was achieved using a Zorbax SB-C8 column
      with gradient elution of the mobile phase composed of 0.05 M phosphoric acid and
      acetonitrile. The gradient elution started with 25% (by volume) acetonitrile,
      ramped up linearly to 65% in 6 min, then kept constant until the end of the run.
      The mobile phase was pumped at a flow rate of 1 mL/min. The multiple wavelength
      detector was set at 215 nm and analytes were quantified by measuring their peak
      areas. The retention times for LD and MZ were approximately 4.1 and 8.4 min,
      respectively. The reliability and analytical performance of the proposed HPLC
      procedure were statistically validated with respect to linearity, ranges,
      precision, accuracy, selectivity, robustness, detection and quantification
      limits. Calibration curves were linear in the ranges of 5-100 ug/ml for both
      drugs with correlation coefficients > 0.999. Both drugs were subjected to stress
      conditions of hydrolysis, oxidation, photolysis and thermal degradation. The
      proposed method proved to be stability-indicating by the resolution of the two
      analytes from the related substance and potential impurity (2,6-dimethylaniline)
      and from the forced-degradation products. The validated HPLC method was applied
      to the analysis of MZ and LD in the combined oral gel preparation, in which the
      two analytes were successfully quantified and resolved from the pharmaceutical
      additives. The proposed method made use of DAD as a tool for peak identity and
      purity confirmation.

PMID- 22407006
TI  - Optimizing ion channel models using a parallel genetic algorithm on graphical
      processors.
AB  - We have recently shown that we can semi-automatically constrain models of voltage
      gated ion channels by combining a stochastic search algorithm with ionic currents
      measured using multiple voltage-clamp protocols. Although numerically successful,
      this approach is highly demanding computationally, with optimization on a high
      performance Linux cluster typically lasting several days. To solve this
      computational bottleneck we converted our optimization algorithm for work on a
      graphical processing unit (GPU) using NVIDIA's CUDA. Parallelizing the process on
      a Fermi graphic computing engine from NVIDIA increased the speed ~180 times over
      an application running on an 80 node Linux cluster, considerably reducing
      simulation times. This application allows users to optimize models for ion
      channel kinetics on a single, inexpensive, desktop "super computer," greatly
      reducing the time and cost of building models relevant to neuronal physiology. We
      also demonstrate that the point of algorithm parallelization is crucial to its
      performance. We substantially reduced computing time by solving the ODEs
      (Ordinary Differential Equations) so as to massively reduce memory transfers to
      and from the GPU. This approach may be applied to speed up other data intensive
      applications requiring iterative solutions of ODEs.

PMID- 22407007
TI  - Clinical rehabilitation needs the translation from basic neuroscience in daily
      practice.

PMID- 22407008
TI  - An innovative spinal cord injury model for the study of locomotor networks.
AB  - An acute lesion to the spinal cord triggers complex mechanisms responsible for
      amplification of the initial damage and its chronicity. In vitro preparations of
      the rodent spinal cord retain the intrinsic ability to produce locomotor-like
      discharges from lumbar ventral roots and, thus, offer the opportunity to study
      the still unclear process of lesion progression in relation to cell number and
      topography. In addition, these models enable a detailed approach to the molecular
      mechanisms of damage and to pharmacological tools to counteract them. Using the
      rat spinal cord in vitro, our laboratory has shown how to reliably produce
      discrete lesions by applying the glutamate agonist kainate that evokes delayed
      neuronal loss via a non-apoptotic cell death mechanism termed parthanatos.
      Parthanatos is believed to be due to mitochondrial damage and exhaustion of cell
      energy stores caused by hyperactivation of enzymatic systems initially set to
      repair DNA damage. Locomotor network activity is irreversibly destroyed by
      kainate in a virtually all-or-none manner, suggesting destruction of a highly
      vulnerable cell population crucial for the expression of locomotion. Hypoxic
      challenge to the spinal cord together with toxic radicals primarily damages white
      matter cells with deficit (without full suppression) of locomotor network
      function, while neurons are less vulnerable. Pharmacological agents to inhibit
      different targets involved in the early pathophysiology of spinal injury provided
      limited success, indicating that novel approaches based on newly identified steps
      in the biochemical cascade leading to cell death should be investigated for their
      potential to improve the outcome of spinal cord injury.

PMID- 22407010
TI  - A new age for rehabilitation.
AB  - In this review we will describe newly developed techniques that are being used to
      recover levels of motor function after a severe spinal cord injury that have not
      been observed previously. These new approaches include pharmacological
      neuromodulation and/or epidural stimulation of the spinal cord circuitries in
      combination with motor training. By combining the increased levels of
      excitability of the interneuronal spinal circuitries using these interventions
      and the ability of the spinal circuitries to interpret and respond appropriately
      to ongoing complex ensembles of sensory input, the peripheral sensory system can
      become an effective source for the control of motor function. Similar types of
      neuromodulation have been shown to enable the brain to regain functional
      connectivity with the spinal cord circuitries below a clinically complete spinal
      cord lesion. In fact, some level of voluntary control of movement has been
      observed in subjects with complete paralysis in the presence of epidural
      stimulation. The biological mechanisms thought to underlie the recovery of motor
      function after a severe spinal cord injury are based on decades of research on a
      wide range of animal models. Fortunately the extensive conservation of neural
      mechanisms of motor control has provided a window for gaining considerable
      insight into the mechanisms of recovery of motor function in humans.

PMID- 22407009
TI  - Cortical networks subserving upper limb movements in primates.
AB  - In all primates, the cortical control of hand and arm movements is initiated and
      controlled by a network of cortical regions including primary motor cortex (M1),
      premotor cortex (PMC), and posterior parietal cortex (PPC). These interconnected
      regions are influenced by inputs from especially visual and somatosensory
      cortical areas, and prefrontal cortex. Here we discuss recent evidence showing
      M1, PMC, and PPC can be subdivided into a number of functional zones or domains,
      including several that participate in guiding and controlling hand and arm
      movements. Functional zones can be defined by the movement sequences evoked by
      microstimulation within them, and functional zones related to the same type of
      movement in all three cortical regions are interconnected. The inactivation of a
      functional zone in each of the regions has a different impact on motor behavior.
      Finally, there is considerable plasticity within the networks so that behavioral
      recoveries can occur after damage to functional zones within a network.

PMID- 22407011
TI  - Natalizumab-associated complication? First case of peripheral T cell lymphoma.

PMID- 22407013
TI  - Structure of N-terminal domain of ZAP indicates how a zinc-finger protein
      recognizes complex RNA.
AB  - Zinc-finger antiviral protein (ZAP) is a host factor that specifically inhibits
      the replication of certain viruses, such as HIV-1, by targeting viral mRNA for
      degradation. How ZAP recognizes its target RNA has been unclear. Here we report
      the crystal structure of the N-terminal domain of rat ZAP (NZAP225), the major
      functional domain. The overall structure of NZAP225 resembles a tractor, with
      four zinc-finger motifs located at the bottom. Structural and functional analyses
      identified multiple positively charged residues and two putative RNA-binding
      cavities forming a large putative RNA-binding cleft. ZAP molecules interact to
      form a dimer that binds to a ZAP-responsive RNA molecule containing two ZAP
      binding modules. These results provide insights into how ZAP binds specifically
      to complex target RNA.

PMID- 22407012
TI  - Hedgehog-mediated regulation of PPARgamma controls metabolic patterns in neural
      precursors and shh-driven medulloblastoma.
AB  - Sonic hedgehog (Shh) signaling is critical during development and its aberration
      is common across the spectrum of human malignancies. In the cerebellum, excessive
      activity of the Shh signaling pathway is associated with the devastating
      pediatric brain tumor medulloblastoma. We previously demonstrated that
      exaggerated de novo lipid synthesis is a hallmark of Shh-driven medulloblastoma
      and that hedgehog signaling inactivates the Rb/E2F tumor suppressor complex to
      promote lipogenesis. Indeed, such Shh-mediated metabolic reprogramming fuels
      tumor progression, in an E2F1- and FASN-dependent manner. Here, we show that the
      nutrient sensor PPARgamma is a key component of the Shh metabolic network,
      particularly its regulation of glycolysis. Our data show that in primary
      cerebellar granule neural precursors (CGNPs), proposed medulloblastoma cells-of
      origin, Shh stimulation elicits a marked induction of PPARgamma alongside major
      glycolytic markers. This is also documented in the actively proliferating Shh
      responsive CGNPs in the developing cerebellum, and PPARgamma expression is
      strikingly elevated in Shh-driven medulloblastoma in vivo. Importantly,
      pharmacological blockade of PPARgamma and/or Rb inactivation inhibits CGNP
      proliferation, drives medulloblastoma cell death and extends survival of
      medulloblastoma-bearing animals in vivo. This coupling of mitogenic Shh signaling
      to a major nutrient sensor and metabolic transcriptional regulator define a novel
      mechanism through which Shh signaling engages the nutrient sensing machinery in
      brain cancer, controls the cell cycle, and regulates the glycolytic index. This
      also reveals a dominant role of Shh in the etiology of glucose metabolism in
      medulloblastoma and underscores the function of the Shh -> E2F1 -> PPARgamma axis
      in altering substrate utilization patterns in brain cancers in favor of tumor
      growth. These findings emphasize the value of PPARgamma downstream of Shh as a
      global therapeutic target in hedgehog-dependent and/or Rb-inactivated tumors.

PMID- 22407014
TI  - A telomere-dependent DNA damage checkpoint induced by prolonged mitotic arrest.
AB  - Telomere shortening and disruption of telomeric components are pathways that
      induce telomere deprotection. Here we describe another pathway, in which
      prolonged mitotic arrest induces damage signals at telomeres in human cells.
      Exposure to microtubule drugs, kinesin inhibitors, proteasome inhibitors or the
      disruption of proper chromosome cohesion resulted in the formation of damage foci
      at telomeres. Induction of mitotic telomere deprotection coincided with
      dissociation of TRF2 from telomeres, telomeric 3'-overhang degradation and ATM
      activation, and deprotection could be suppressed by TRF2 overexpression or
      inhibition of Aurora B kinase. Normal cells that escaped from prolonged mitotic
      arrest halted in the following G1 phase, whereas cells lacking p53 continued to
      cycle and became aneuploid. We propose a telomere-dependent mitotic-duration
      monitoring system that reacts to improper progression through mitosis.

PMID- 22407016
TI  - Diverse HIV viruses are targeted by a conformationally dynamic antiviral.
AB  - Rhesus macaque TRIMCyp (RhTC) is a potent primate antiviral host protein that
      inhibits the replication of diverse HIV viruses. Here we show that it has
      acquired the ability to target multiple viruses by evolving an active site that
      interconverts between multiple conformations. Mutations that have relieved active
      site constraints allow RhTC to dynamically sample conformational space, including
      radically different conformers that target both HIV-1 and HIV-2 viruses.
      Introduction of a reversible constraint into RhTC allows specificity to be
      switched between a single conformation specific for HIV-1 and a dynamic ensemble
      that targets multiple viruses. These results show that conformational diversity
      can be used to expand the target diversity of innate immune receptors by
      supplementing their limited genetic variability with variability in protein
      structure.

PMID- 22407017
TI  - The emergence of global attention to health systems strengthening.
AB  - After a period of proliferation of disease-specific initiatives, over the past
      decade and especially since 2005 many organizations involved in global health
      have come to direct attention and resources to the issue of health systems
      strengthening. We explore how and why such attention emerged. A qualitative
      methodology, process-tracing, was used to construct a case history and analyse
      the factors shaping and inhibiting global political attention for health systems
      strengthening. We find that the critical factors behind the recent burst of
      attention include fears among global health actors that health systems problems
      threaten the achievement of the health-related Millennium Development Goals,
      concern about the adverse effects of global health initiatives on national health
      systems, and the realization among global health initiatives that weak health
      systems present bottlenecks to the achievement of their organizational
      objectives. While a variety of actors now embrace health systems strengthening,
      they do not constitute a cohesive policy community. Moreover, the concept of
      health systems strengthening remains vague and there is a weak evidence base for
      informing policies and programmes for strengthening health systems. There are
      several reasons to question the sustainability of the agenda. Among these are the
      global financial crisis, the history of pendulum swings in global health and the
      instrumental embrace of the issue by some actors.

PMID- 22407015
TI  - A conserved proline switch on the ribosome facilitates the recruitment and
      binding of trGTPases.
AB  - When elongation factor G (EF-G) binds to the ribosome, it first makes contact
      with the C-terminal domain (CTD) of L12 before interacting with the N-terminal
      domain (NTD) of L11. Here we have identified a universally conserved residue,
      Pro22 of L11, that functions as a proline switch (PS22), as well as the
      corresponding center of peptidyl-prolyl cis-trans isomerase (PPIase) activity on
      EF-G that drives the cis-trans isomerization of PS22. Only the cis configuration
      of PS22 allows direct contact between the L11 NTD and the L12 CTD. Mutational
      analyses of both PS22 and the residues of the EF-G PPIase center reveal their
      function in translational GTPase (trGTPase) activity, protein synthesis and cell
      survival in Escherichia coli. Finally, we demonstrate that all known universal
      trGTPases contain an active PPIase center. Our observations suggest that the cis
      trans isomerization of the L11 PS22 is a universal event required for an
      efficient turnover of trGTPases throughout the translation process.

PMID- 22407018
TI  - Cost-effectiveness of Haemophilus influenzae type b (Hib) vaccine introduction in
      the universal immunization schedule in Haryana State, India.
AB  - OBJECTIVE: In India, Haemophilus influenzae type b (Hib) vaccine introduction in
      the universal immunization programme requires evidence of its potential health
      impact and cost-effectiveness, as it is a costly vaccine. Since childhood
      mortality, vaccination coverage and health service utilization vary across
      states, the cost-effectiveness of introducing Hib vaccine was studied in Haryana
      state. METHODOLOGY: A mathematical model was used to compare scenarios with and
      without Hib vaccination to estimate the cost-effectiveness of Hib vaccine in
      Haryana from 2010 to 2024. Demographic and National Family Health Surveys were
      used to estimate vaccination coverage and mortality rates among children under 5.
      Hib pneumonia, Hib meningitis and invasive Hib disease incidence were based on
      Indian studies. Vaccine and syringe prices of the UNICEF supply division were
      used. Cost-effectiveness from government and societal perspectives was calculated
      as the net incremental cost per unit of health benefit gained [disability
      adjusted life years (DALYs) averted, life years saved, Hib cases averted, Hib
      deaths averted]. Sensitivity analysis was done using variation in parameter
      estimates among different states of India. FINDINGS: The incremental cost of Hib
      vaccine introduction from a government and a societal perspective was estimated
      to be US$81.4 and US$27.5 million, respectively, from 2010 to 2024. Vaccination
      of 73.3, 71.6 and 67.4 million children with first, second and third dose of
      pentavalent vaccine, respectively, would avert 7 067 817 cases, 31 331 deaths and
      994 564 DALYs. Incremental cost per DALY averted from a government (US$819) and a
      societal perspective (US$277) was found to be less than the per capita gross
      national income of India in 2009. In sensitivity analysis, Hib vaccine
      introduction remained cost-effective for India. CONCLUSION: Hib vaccine
      introduction is a cost-effective strategy in India.

PMID- 22407019
TI  - Fukushima nuclear power station: what happened? Why all health care professionals
      need radiation training.

PMID- 22407020
TI  - Inverted u-shaped purse and rotation flaps: correcting the inferoposterior
      deformity of reconstructed ears after canaloplasty of the external auditory
      meatus.
AB  - BACKGROUND: After patients with congenital microtia receive external ear canal
      plasty, the mastoid area usually has insufficient space for ear reconstruction.
      Hence, after ear reconstruction, an inferoposterior position deformity of the ear
      appears to some extent. Using inverted U-shaped purse and rotation flaps can
      correct this deformity effectively. METHODS: From May of 2009 to September of
      2011, five patients received the described procedures in the authors' department.
      Inverted U-shaped purse and rotation flaps were used for all the patients. The
      inverted U-shaped purse flap was used to reduce the area of the canal orifice and
      to lower the position, and the rotation flap was applied to turn the ear in a
      more superoposterior position. Two patients also received full-thickness skin
      grafting to cover the secondary wound. In four patients, V-Y-plasty or Z-plasty
      was used to adjust the flap transition. RESULTS: For the five patients, the
      distances between the ear antihelix and canal orifice were shortened, and the
      areas of the canal orifice were diminished. The retroversion of the auricle was
      corrected in various degrees, and the angles of the long axis of the auricle and
      the horizontal line were increased an average of 14.4 degrees . The vertical
      distance between the top of the helix and the center of the canal orifice was
      increased an average of 15.2 mm. A slight dog ear deformity in front of the crus
      of the helix was left after the operation, but it was alleviated in the follow-up
      period. CONCLUSION: By using inverted U-shaped purse and rotation flaps, the
      inferoposterior position deformity of the reconstructed ear after external ear
      canal plasty in congenital microtia can be resolved effectively. LEVEL OF
      EVIDENCE IV: This journal requires that authors assign a level of evidence to
      each article. For a full description of these Evidence-Based Medicine ratings,
      please refer to the Table of Contents or the online Instructions to Authors
      http://www.springer.com/00266.

PMID- 22407021
TI  - Adjustment disorders: prevalence in a representative nationwide survey in
      Germany.
AB  - OBJECTIVES: This is the first study to estimate the prevalence of adjustment
      disorder (AjD) in the general population. A new conceptualisation of AjD as a
      stress response syndrome was applied, which allowed AjD to be assessed directly
      from its symptom profile, including intrusive, avoidance and failure-to-adapt
      symptoms (Maercker et al., Psychopathology 40:135-146, 2007). METHODS: Prevalence
      rates of distressing life events and AjD were estimated from a representative
      sample of the German general population (n = 2,512) with a broad age range (14-93
      years). A questionnaire including a life events checklist and self-rating
      questions that assessed AjD symptoms and symptom duration were personally handed
      out by an interviewer. RESULTS: The prevalence of AjD fulfilling the criterion of
      clinically significant impairment was 0.9%; a further 1.4% of the sample was
      diagnosed with AjD without fulfilling the impairment criterion. In ~72.5% of AjD
      cases, symptoms had developed 6-24 months prior to assessment. AjD was most often
      associated with acute events such as moving or chronic stressors such as serious
      illness, conflicts at the respondent's job or with friends or neighbours (with
      ~5% conditional probability each). CONCLUSIONS: The results correspond with the
      few other studies that have examined the prevalence of AjD, even though a new
      conceptualisation of the disorder was used. Explorative results regarding the
      duration of AjD syndromes and symptoms call for further redefinition and
      empirical investigation of this under-researched mental condition.

PMID- 22407022
TI  - A cross-sectional, multicentre study of the therapeutic management of multiple
      sclerosis relapses in Italy.
AB  - Despite the existence of therapeutic guidelines, management of multiple sclerosis
      relapse remains heterogeneous. Optimisation of relapse outcome demands an
      improved understanding of the neurologist's therapeutic attitude towards relapse
      management, which is the aim of this study. Neurologists from 13 multiple
      sclerosis centres completed a questionnaire every time they assessed multiple
      sclerosis relapses. The questionnaire requested a guided description of the
      relapse's clinical characteristics and an indication of the prescribed therapy,
      supported with up to 3 out of 20 suggested reasons. Over 3 months, 368
      questionnaires were collected. Median percentage (%) of 21 relapses resulting in
      a prescription was 88.9%. Corticosteroids represented the most frequent
      prescription. A short-course of high-dose intravenous methylprednisolone was the
      most used corticosteroid (73.7%). Treatment was administrated mainly in day case
      unit (80.0%) and at home (13.6%). A tapered therapy was prescribed to 28.8% of
      patients. Neurologists' therapeutic decisions were driven mainly by relapse
      severity (45.3%) and symptom evolution (24.2%). Our study confirms the
      therapeutic attitude of multiple sclerosis specialists in treating relapses with
      high-dose intravenous corticosteroids in a day hospital setting, with a tapering
      in a proportion of cases. The main reasons for prescription are relapse severity
      and symptom evolution.

PMID- 22407023
TI  - Study of a family in the province of Matera presenting with glucose-6-phosphate
      dehydrogenase deficiency and Gilbert's syndrome.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a recessive X-linked trait,
      is the most common enzyme deficiency in the world. The most devastating clinical
      consequence of this deficit is severe neonatal jaundice, which results in
      sensorineural deficit, and severe haemolytic anemia. However, patients may be
      asymptomatic. The most common clinical sign is hyperbilirubinemia (h?), that is
      also related to Gilbert's syndrome, a condition associated with the promoter
      polymorphism of the UDP-glucuronosyltransferase 1 (UGT1A1) gene. The aim of this
      study was to underline (as is usually done by DNA molecular analysis) to detect
      and to clarify the genetic deficiency that is the reason of the disorder in
      question. In this study, different techniques were applied to analyse a family of
      four individuals presenting with hyperbilirubinemia: bilirubinic dosage,
      electrophoresis and enzymatic activity dosage of G6PD; molecular analysis of the
      UGT1A promoter to detect a thymine-adenine (TA) insertion, that causes the
      [A(TA)7TAA] mutation. The results showed that in certain cases, the presence of
      hyperbilirubinemia is not only associated with G6PD deficiency, but may be caused
      by the co-presence of a mutation in the UGTA1 promoter related to Gilbert's
      syndrome. As being affected by these two conditions predisposes to adverse
      effects towards certain drug treatments, it is advisable to study the UGTA1 gene
      before prescribing drugs for specific antineoplastic or retroviral treatment. We
      emphasize that investigating both the UGT1A gene and G6PD activity is the most
      reliable way to make a correct differential diagnosis.

PMID- 22407024
TI  - Interplay between Fe 3d and Ce 4f magnetism and Kondo interaction in CeFeAs(1
      x)P(x)O probed by 75As and 31P NMR.
AB  - A detailed (31)P (I = 1/2) and (75)As (I = 3/2) NMR study on polycrystalline
      CeFeAs(1-x)P(x)O alloys is presented. The magnetism of CeFeAsO changes
      drastically upon P substitution on the As site. CeFePO is a heavy fermion system
      without long-range order whereas CeFeAsO exhibits an Fe 3d SDW type of ordering
      accompanied by a structural transition from tetragonal (TT) to orthorhombic (OT)
      structure. Furthermore, Ce 4f(1) orders antiferromagnetically (AFM) at low
      temperature. At the critical concentration where the Fe magnetism is diminished
      the Ce-Ce interaction changes to a ferromagnetic (FM) type of ordering. Three
      representative samples of the CeFeAs(1-x)P(x)O (x = 0.05, 0.3 and 0.9) series are
      systematically investigated. (1) For the x = 0.05 alloy a drastic change of the
      linewidth at 130 K indicates the AFM-SDW type of ordering of Fe and the
      structural change from the TT to the OT phase. The linewidth roughly measures the
      internal field in the ordered state and the transition is most likely first
      order. The small and nearly constant shift from (31)P and (75)As NMR suggests the
      presence of competing hyperfine interactions between the nuclear spins and the 4f
      and 3d ions of Ce and Fe. (2) For the x = 0.3 alloy, the evolution of the Fe-SDW
      type of order takes place at around 70 K corroborating the results of bulk
      measurement and MUSR. Here we found evidence for phase separation of paramagnetic
      and magnetic SDW phases. (3) In contrast to the heavy fermion CeFePO for the x =
      0.9 alloy a phase transition is found at 2 K. The field-dependent NMR shift gives
      evidence of FM ordering. Above the ordering the spin-lattice relaxation rate
      (31)(1/T(1)) shows unconventional, non-Korringa-like behaviour which indicates a
      complex interplay of Kondo and FM fluctuations.

PMID- 22407025
TI  - Loss-of-function mutations in filaggrin gene associate with psoriasis vulgaris in
      Chinese population.
AB  - Loss-of-function mutations in filaggrin gene (FLG; OMIM #135940) have been
      reported to cause the semi-dominant keratinizing disorders such as ichthyosis
      vulgaris (IV; OMIM #146700) and atopic dermatitis (AD; OMIM #605803). Recent
      linkage analysis and immunohistochemical studies suggest the possible
      contribution of FLG to psoriatic susceptibility. However, no susceptibility
      variant in FLG gene associated with psoriasis (OMIM #177900) has been identified.
      In this study, we identified a non-sense mutation of FLG (p.K4022X) in a Chinese
      psoriasis/IV coexisting family. The homozygous p.K4022X mutation was detected in
      a psoriasis patient, whereas the heterozygous p.K4022X mutation was identified in
      two IV patients and four apparently normal family members. We also genotyped
      p.K4022X variant in 441 sporadic Chinese psoriasis patients and found homozygous
      mutation in two patients, while no homozygous variant was found in 500 control
      individuals. After sequencing the entire coding region of FLG gene in 441
      psoriasis patients, we identified another five mutations (p.R826X, p.W2583X,
      c.7945delA, c.3321delA and p.Q2417X). Although all six FLG mutations as a whole
      was not significantly associated with psoriasis (P = 0.105), mutation p.K4022X
      was significantly associated with psoriasis (P < 0.05). Our data thus indicates
      an association of FLG with psoriasis in Chinese population.

PMID- 22407026
TI  - Coexisting mutations/polymorphisms of the long QT syndrome genes in patients with
      repaired Tetralogy of Fallot are associated with the risks of life-threatening
      events.
AB  - Coexisting long QT gene mutations/polymorphisms in Tetralogy of Fallot (TOF)
      patients may aggravate the repolarization abnormality from cardiac repair. We
      investigated the impact of these genes on the risk of life-threatening events.
      Genetic variants of the three common long QT genes were identified from patients
      with repaired TOF. Life-threatening events were defined as sudden cardiac death
      and hemodynamic unstable ventricular arrhythmia. Biophysical characterization of
      the alleles of the genetic variants was performed using a whole-cell voltage
      clamp with expression in Xenopus oocytes. A total of 84 patients (56.0 % male
      with 1,215 patients-year follow-up) were enrolled. Six rare variants and six non
      synonymous single nucleotide polymorphisms (SNPs) were found in 40 (47.6 %)
      patients. Life-threatening events occurred in five patients; four received
      implantable cardioverter defibrillator and one died of sudden cardiac death. Life
      threatening events occurred more often in those with genetic variants than those
      without (5/40 vs. 0/44, P = 0.021); particularly, the hERG or SCN5A gene
      mutations/polymorphisms (2/5 vs. 3/79, P = 0.027 and 5/27 vs. 0/57, P = 0.003,
      respectively). Among the five patients with life-threatening events, three had
      compound variants (hERG p.M645R/SCN5A p.R1193Q, hERG p.K897T/SCN5A p.H558R, and
      KVLQT1 p.G645S/SCN5A p.P1090L), that also increased the risk of events. Their QTc
      and JTc were all prolonged. Functional study of the novel variant (hERG gene
      p.M645R) from patients with life-threatening events revealed a dominant negative
      effect. In conclusion, in repaired TOF patients, coexisting long QT
      mutations/polymorphisms might have additive effects on the repolarization
      abnormality from surgery and thereby increase the risks of life-threatening
      events.

PMID- 22407027
TI  - Adaptive evolution of loci covarying with the human African Pygmy phenotype.
AB  - African Pygmies are hunter-gatherer populations from the equatorial rainforest
      that present the lowest height averages among humans. The biological basis and
      the putative adaptive role of the short stature of Pygmy populations has been one
      of the most intriguing topics for human biologists in the last century, which
      still remains elusive. Worldwide convergent evolution of the Pygmy size suggests
      the presence of strong selective pressures on the phenotype. We developed a novel
      approach to survey the genetic architecture of phenotypes and applied it to study
      the genomic covariation between allele frequencies and height measurements among
      Pygmy and non-Pygmy populations. Among the regions that were most associated with
      the phenotype, we identified a significant excess of genes with pivotal roles in
      bone homeostasis, such as PPPT3B and the height associated SUPT3H-RUNX2. We
      hypothesize that skeletal remodeling could be a key biological process underlying
      the Pygmy phenotype. In addition, we showed that these regions have most likely
      evolved under positive selection. These results constitute the first genetic hint
      of adaptive evolution in the African Pygmy phenotype, which is consistent with
      the independent emergence of the Pygmy height in other continents with similar
      environments.

PMID- 22407028
TI  - Assessment of Epstein-Barr virus in blood from patients with multiple sclerosis.
AB  - Viruses such as Epstein-Barr virus (EBV) which can establish latent infections in
      the central nervous system or the immune system have been associated with chronic
      neurological disorders, including multiple sclerosis. Results vary, therefore the
      aim of this study was to investigate the presence of EBV using both viral DNA and
      antibody screening techniques, using PCR and ELISA assays respectively, to
      evaluate viral presence in blood from control subjects and patients with multiple
      sclerosis. Viral gene sequences for latent proteins EBNA-1 and LMP-1 and lytic
      gene BamH1-W were present equally in both patients and controls (<7%). Anti-EBV
      VCA IgG positive cases were present in >99% of all study subjects, and anti-EBV
      VCA IgG immune status ratio showed a near-significant positive correlation with
      the EDSS in patients with multiple sclerosis. In contrast, Anti-EBV-VCA IgM
      positive cases were significantly increased in patients (controls: 23.3%;
      patients; 41.9%; P = 0.046). The IgM to IgG immune status ratio was near
      significantly higher in patients with relapse episodes in the year preceding
      blood sampling (P = 0.058). Results from this and previous studies have shown
      higher prevalence rates for EBV evaluating anti-EBV IgM positive cases against
      viral DNA positive cases. Also, IgM, an innate immune response, showed an
      association with relapse episodes, suggesting viral re-activation as a
      contributing factor to these relapses.

PMID- 22407029
TI  - P53 and the proteasome regulate androgen receptor activity.
AB  - Mutual regulation of expression between p53 and AR has been reported. To further
      investigate the role of p53 in the regulation of AR expression, an ARE-Luciferase
      vector was inserted into LNCaP and into LNCaP-sip53 transfectants, and AR
      activity was quantitatively estimated after treatment with proteasome inhibitors.
      LNCaP expresses a mutated form of AR. Therefore, to investigate whether p53 can
      modulate the expression of wild-type (wt) of AR, we transfected PC3-wtAR with a
      p53 vector together with ARE-Luc and showed that p53 expression decreased DHT
      dependent activity of wtAR. Since proteasomes also participate in AR
      transcriptional activity, we investigated the role of p53 in proteasome-dependent
      inhibition of AR activity. More than 80% of AR activity was inhibited by 3 MUM of
      lactacystin in LNCaP whereas no inhibition was noted in LN-sip53. We also found
      that lactacystin decreased AR-DNA binding 3-fold in LNCaP but no binding decrease
      was observed in LN-sip53. Taken together, our data show that the inhibitory
      effects of proteasome inhibitors are dependent on p53 status, at least in
      prostate cancer. Therefore, the role of p53 during treatment with proteasome
      inhibitors in different tumors should be further investigated.

PMID- 22407030
TI  - Vasculogenic mimicry is a marker of poor prognosis in prostate cancer.
AB  - We investigated the role of vasculogenic mimicry (VM) in the progression of
      prostate cancer (PCa). Ninety-six patients who had undergone prostatectomy for
      treatment of PCa and for whom a complete record of clinical and follow-up data
      were available were reviewed. VM and matrix metalloproteinase-2 (MMP-2) were
      detected by immunohistochemical staining in frozen tissue sections. Relationship
      between VM and clinicopathological variables was analyzed statistically.
      Multivariate analyses were performed to assess the prognostic significance of VM.
      Results showed that out of the 96 PCa cases studied here, VM was detectable in 24
      (25%) and was positively correlated with preoperative prostate-specific antigen
      (PSA) level, Gleason score, pathological stage, lymph node metastasis, seminal
      vesicle invasion, distant metastasis and PSA doubling time (PSADT). Univariate
      analysis showed that VM, PSA level, Gleason score, distant metastasis and PSADT
      were correlated with overall survival (OS), while VM, Gleason score, distant
      metastasis, local recurrence and PSADT were correlated with disease-free survival
      (DFS). Multivariable analysis indicated that the presence of VM, higher Gleason
      score and distant metastasis were the adverse predictors of OS and DFS. A higher
      widespread staining for MMP-2 was correlated with the VM-positive subgroup. In
      conclusion, VM mainly exists in the high risk PCa patients and is an independent
      marker of poor prognosis.

PMID- 22407031
TI  - Novel lower critical solution temperature phase transition materials effectively
      control osmosis by mild temperature changes.
AB  - Osmosis can be controlled reversibly and effectively by mild temperature changes
      based on novel thermosensitive solutes with LCST transition. The nBu-TAEA
      thermosensitive solution can draw fresh water from seawater at temperatures less
      than the phase separation temperature, and the osmotic flow was reversed at
      higher temperatures.

PMID- 22407032
TI  - Design of switchable wettability sensor for paraquat based on clicking
      calix[4]arene.
AB  - A calix[4]arene acetylene (C4AE)-modified gold surface is successfully
      constructed in situ via click chemistry. The functionalized surface is used for
      selective recognition of paraquat by a wettability switch. Impedance measurements
      showed that the surface also expresses recognition for paraquat with a high
      sensitivity of 10 pM. The recognition mode, based on host-guest inclusion, is
      studied by computational calculations and the possible mechanism is analyzed.

PMID- 22407033
TI  - Dynamic hyperinflation on exertion: much remains unknown.

PMID- 22407034
TI  - [Let us be cautious and prevent unnecessary patient harm].

PMID- 22407035
TI  - Extracorporeal membrane oxygenation in severe hypoxemia: time for reappraisal?
AB  - In 2009, during the influenza A (H1N1) epidemic, there were many reported cases
      of pulmonary infection with severe hypoxemia that was refractory to the
      ventilatory strategies and rescue therapies commonly used to treat patients with
      severe acute respiratory distress syndrome. Many of those cases were treated with
      extracorporeal membrane oxygenation (ECMO), which renewed international interest
      in the technique. The Extracorporeal Support Study Group was created in order to
      practice ECMO and to employ it in the treatment of patients with severe
      hypoxemia. In this article, we discuss the indications for using ECMO and report
      the case of a patient with refractory hypoxemia who was successfully treated with
      ECMO.

PMID- 22407036
TI  - Dynamic hyperinflation during treadmill exercise testing in patients with
      moderate to severe COPD.
AB  - OBJECTIVE: To characterize the presence, extent, and patterns of dynamic
      hyperinflation (DH) during treadmill exercise testing in patients with moderate
      to severe COPD. METHODS: This was a cross-sectional study involving 30 non
      hypoxemic patients (FEV1= 43 +/- 14% of predicted) who were submitted to a
      cardiopulmonary exercise test on a treadmill at a constant speed (70-80% of
      maximum speed) to the tolerance limit (Tlim). Serial inspiratory capacity (IC)
      maneuvers were used in order to assess DH. RESULTS: Of the 30 patients studied,
      19 (63.3%) presented with DH (DH+ group), having greater pulmonary function
      impairment at rest than did those without DH (DH- group). None of the variables
      studied correlated with exercise tolerance in the DH- group, whereas Tlim, IC,
      and perception of dyspnea during exercise did so correlate in the DH+ group (p <
      0.05). In the DH+ group, 7 and 12 patients, respectively, presented with a
      progressive and a stable pattern of DH (DeltaIC Tlim,2min = -0.28 +/- 0.11 L vs.
      0.04 +/- 0.10 L; p < 0.01). Patients with a progressive pattern of DH presented
      with higher perception of dyspnea/Tlim rate and lower exercise tolerance than did
      those with a stable pattern (354 +/- 118 s and 465 +/- 178 s, respectively; p <
      0.05). CONCLUSIONS: The presence of DH is not a universal phenomenon during
      walking in COPD patients, even in those with moderate to severe airflow
      limitation. In the patients who presented DH, a progressive pattern of DH had a
      greater impact on exercise tolerance than did a stable pattern of DH.

PMID- 22407037
TI  - Occurrence of asthma symptoms and of airflow obstruction in amateur swimmers
      between 8 and 17 years of age.
AB  - OBJECTIVE: To determine the prevalence of asthma symptoms and of airflow
      obstruction in amateur swimmers between 8 and 17 years of age, as well as to
      assess the awareness of asthma and asthma management among these swimmers, their
      parents, and their coaches. METHODS: Our sample comprised 1,116 amateur swimmers
      who completed a modified version of the International Study of Asthma and
      Allergies in Childhood written questionnaire, to which questions regarding the
      reasons to initiate swimming and regarding asthma management had been added. In
      addition, the participants underwent spirometry prior to a swimming competition.
      RESULTS: The prevalence of asthma symptoms in the last 12 months was 11.5%, and
      327 (29.4%) of the participants reported "wheezing or whistling" in the past. Of
      the 223 swimmers who reported "asthma ever" or "bronchitis ever", only 102
      (45.7%) reported having ever been treated: the most common "treatment" was
      swimming (in 37.3%), and only 12.7% used inhaled corticosteroids. Of the 254
      participants (22.7%) with airflow obstruction, only 52 (20.5%) reported having
      asthma symptoms. CONCLUSIONS: Asthma symptoms are present in amateur swimmers,
      and a considerable number of such swimmers have airflow obstruction without
      symptoms. It is therefore likely that the prevalence of asthma is underestimated
      in this population. It is worrisome that, in our study sample, the swimmers
      previously diagnosed with asthma were not using the recommended treatments for
      asthma. The clinical implications of these findings underscore the importance of
      implementing educational measures for amateur swimmers, as well as for their
      parents and coaches, to help them recognize asthma symptoms and the consequent
      risks in the sports environment, in order to allow prompt diagnosis and early
      clinical intervention.

PMID- 22407038
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis
      and staging of mediastinal lymphadenopathy: initial experience in Brazil.
AB  - OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS
      TBNA) is a new method for the diagnosis and staging of mediastinal lymph nodes.
      The objective of this study was to evaluate the preliminary results obtained with
      EBUS-TBNA in the diagnosis of lesions and mediastinal lymph node staging.
      METHODS: We evaluated patients with tumors or mediastinal adenopathy, diagnosed
      with or suspected of having lung cancer. The procedures were performed with the
      patients under sedation or under general anesthesia. Material was collected by
      EBUS-TBNA, after which it was prepared on slides, fixed in either absolute
      alcohol (for cytology) or formalin (for cell-block analysis). RESULTS: We
      included 50 patients (30 males). The mean age was 58.3 +/- 13.5 years. We
      performed 201 biopsies of 81 lymph nodes or mediastinal masses (mean of 2.5
      punctures/biopsy). The quantity of material was considered sufficient for
      cytology in 37 patients (74%), 21 (57%) of whom were thus diagnosed with
      malignancy. Of the remaining 16 patients, 1 was diagnosed with tuberculosis, 6
      entered clinical follow-up, and 9 underwent further investigation (2 diagnosed
      with neoplasm-false-negative results). The yield was higher when the procedure
      was performed for diagnostic purposes, as well as being higher in patients with
      lesions in multiple stations and in biopsies involving the subcarinal lymph node
      station. One patient had endobronchial bleeding, which was resolved with local
      measures. There were no deaths among the patients evaluated. CONCLUSIONS: This
      preliminary experience shows that EBUS-TBNA is a safe procedure. Our diagnostic
      yield, although lower than that reported in the literature, was consistent with
      the learning curve for the method.

PMID- 22407039
TI  - High-resolution computed tomography scores in cystic fibrosis patients colonized
      with Pseudomonas aeruginosa or Staphylococcus aureus.
AB  - OBJECTIVE: To compare HRCT findings in cystic fibrosis (CF) patients chronically
      colonized with Pseudomonas aeruginosa or Staphylococcus aureus using the modified
      Bhalla CT scoring system, as well as to evaluate intraobserver and interobserver
      reliability of the method. METHODS: This was a retrospective cross-sectional
      study involving 41 CF patients, 26 of whom were chronically colonized with P.
      aeruginosa (Pa group), and 15 of whom were colonized with S. aureus (Sa
      group).Two independent radiologists evaluated the HRCT scans of these patients
      using the modified Bhalla CT scoring system in two different moments.
      Intraobserver and interobserver reliability was calculated using the intraclass
      correlation coefficient (ICC). RESULTS: There was good intraobserver and
      interobserver agreement (ICC > 0.8). Scores were higher in the Pa group than in
      the Sa group for observer 1 (mean, 13.50 +/- 3.90; median, 13.5 vs. mean, 5.00 +/
      5.28; median, 3.0) and for observer 2 (mean, 11.96 +/- 5.07; median, 12.0 vs.
      mean, 5.07 +/- 5.65; median, 5.0). In addition, HRCT findings, such as
      bronchiectasis, bronchial wall thickening, mucus plugging, generation of
      bronchial divisions, and mosaic attenuation/perfusion pattern, were more
      prevalent in the Pa group. CONCLUSIONS: The modified Bhalla CT scoring system was
      reproducible and reliable for use in the evaluation of HRCT scans, allowing
      distinctions to be drawn between the two groups of patients under study. The
      higher scores in the Pa group provided evidence of greater pulmonary impairment
      in that group.

PMID- 22407040
TI  - Cystic fibrosis transmembrane conductance regulator gene mutations and
      glutathione S-transferase null genotypes in cystic fibrosis patients in Brazil.
AB  - OBJECTIVE: To determine the effects that mutation of the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene and deletion of the glutathione S
      transferase (GST) genes mu-1 (GSTM1) and theta-1 (GSTT1) have on the clinical
      course of cystic fibrosis (CF) in patients residing in the southeastern region of
      Brazil. METHODS: The study sample consisted of all consecutive CF patients
      treated at the Hospital de Clinicas School of Medical Sciences of the State
      University at Campinas between March of 2002 and March of 2005. We included 66 CF
      patients. Genomic DNA was analyzed by polymerase chain reaction and restriction
      endonuclease digestion for the identification of the genotypes. RESULTS: The
      DF508 mutation of the CFTR gene was found in 44 patients (66.7%). The null
      genotypes GSTM1, GSTT1 and GSTM1/GSTT1 were found in 40.9%, 15.2%, and 3.0% of
      the patients, respectively. The DF508 CFTR mutation was more common in patients
      diagnosed with CF before 2.5 years of age than in those diagnosed later (75.5%
      vs. 41.2%; p = 0.008). The frequency of the DF508 CFTR mutation, as well as of
      the GSTM1 and GSTT1 genotypes, was not found to be associated with gender,
      ethnicity, pulmonary disease status, or pancreatic disease status. CONCLUSIONS:
      When the patients were stratified by clinical and epidemiological features, the
      frequencies of the GSTM1 and GSTT1 null genotypes were similar, suggesting that
      the inherited absence of these enzymatic pathways does not alter the course of
      CF. However, the high frequency of the DF508 CFTR mutation found in younger
      children suggests that it influences the age at diagnosis of CF in this region of
      Brazil.

PMID- 22407041
TI  - Pandemic influenza A (H1N1) 2009: risk factors for hospitalization.
AB  - OBJECTIVE: To evaluate pandemic influenza A (H1N1) 2009 in hospitalized patients
      in order to identify risk factors for hospitalization and, consequently, for the
      worsening of the disease. METHODS: This retrospective observational study was
      conducted between March and December of 2010. The data were collected from the
      Brazilian Ministry of Health National Case Registry Database. We included only
      patients (inpatients and outpatients) in whom H1N1 infection was confirmed (via
      laboratory testing) during the study period. The variables regarding demographic
      and clinical characteristics were statistically evaluated in order to compare the
      hospitalization rates in the presence or absence of these factors. Risk factors
      were identified by logistic regression analysis. RESULTS: We included 4,740
      patients with laboratory confirmation of H1N1 infection. Of these, 1,911
      individuals were hospitalized, and 258 (13.5%) died. The risk factors for
      hospitalization were age (20-29 years), African or Indigenous ethnicity, presence
      of specific comorbidities (heart disease, lung disease, kidney disease,
      hemoglobinopathy, immunosuppression, diabetes, obesity, puerperium, and smoking),
      a high number of comorbidities, and specific symptoms (dyspnea, diarrhea,
      vomiting, chest pain, hemoptysis, pneumonia, and wheezing). Higher levels of
      education and early use of oseltamivir were found to be protective factors.
      Hospitalization contributed to an increase in survival. CONCLUSIONS: Knowledge of
      the epidemiological characteristics that can be associated with hospitalization,
      disease severity, and mortality can be helpful in the adoption of preventive
      measures, as well as in the early diagnosis and treatment of disease, which might
      contribute to the reduction in the numbers of hospitalizations and deaths.

PMID- 22407042
TI  - Streptococcus pneumoniae: susceptibility to penicillin and moxifloxacin.
AB  - OBJECTIVE: To determine the minimum inhibitory concentrations (MICs) of
      parenteral penicillin and moxifloxacin against Streptococcus pneumoniae strains
      isolated at a hospital center. METHODS: In-vitro, prospective study involving 100
      S. pneumoniae isolates collected from patients who had been treated, between
      October of 2008 and July of 2010, at the Hospital das Clinicas complex of the
      University of Sao Paulo School of Medicine, located in the city of Sao Paulo,
      Brazil. The isolates were obtained from respiratory tract cultures or blood
      samples unrelated to meningeal infections, and they were tested for penicillin
      and moxifloxacin susceptibility by E-test. The MIC category interpretations were
      based on updated standards. RESULTS: All isolates were fully susceptible to
      parenteral penicillin (MIC < 2 ug/mL), and, consequently, they were also
      susceptible to amoxicillin, ampicillin, third/fourth generation cephalosporins,
      and ertapenem. Of the S. pneumoniae strains, 99% were also susceptible to
      moxifloxacin, and only one strain showed an MIC = 1.5 ug/mL (intermediate).
      CONCLUSIONS: Our results showed high susceptibility rates to parenteral
      penicillin and moxifloxacin among S. pneumoniae isolates unrelated to meningitis,
      which differs from international reports. Reports on penicillin resistance should
      be based on updated breakpoints for non-meningitis isolates in order to guide the
      selection of an antimicrobial therapy and to improve the prediction of the
      clinical outcomes.

PMID- 22407043
TI  - Smoking among patients hospitalized at a university hospital in the south of
      Brazil: prevalence, degree of nicotine dependence, and motivational stage of
      change.
AB  - OBJECTIVE: To determine the prevalence and profile of smoking among hospitalized
      patients at a university hospital in the south of Brazil. METHODS: This was a
      descriptive cross-sectional study involving patients over 18 years of age
      hospitalized for over 24 h at the Federal University of Santa Catarina University
      Hospital, located in the city of Florianopolis, Brazil. The patients were
      interviewed on two distinct occasions. We collected demographic data,
      socioeconomic data, and data regarding smoking. RESULTS: We interviewed 235
      patients: 44 (18.7%) were smokers; 77 (32.8%) were former smokers; 114 (48.5%)
      were nonsmokers; and 109 (46.7%) were passive smokers. The mean age of the
      smokers was 45.7 +/- 15.2 years, and 29 (65.9%) were male. Among the smokers, the
      median age at smoking initiation was 15 years; the mean smoking history was 32 +/
      30.2 pack-years; 36 (81.9%) smoked up to 20 cigarettes/day; 20 (45.4%) had a
      high or very high degree of nicotine dependence; 32 (72.7%) had already tried to
      quit smoking; 39 (88.7%) would like to quit smoking; 32 (72.7%) would accept
      smoking cessation treatment; 13 (29.5%) smoked during hospitalization; and 13
      (29.5%) suffered withdrawal syndrome. Regarding the motivation to quit smoking,
      the number of patients in the "preparation" and "action" stages of change
      increased from admission to discharge (from 31.8% to 54.8%). CONCLUSIONS: The
      prevalence of smoking in this study was similar to that reported in other studies
      conducted in Brazil. The results suggest that our sample was significant
      regarding the population of hospitalized smokers, who are motivated to quit
      smoking during hospitalization and require a systematized approach for doing so.

PMID- 22407044
TI  - Audiometric evaluation of patients treated for pulmonary tuberculosis.
AB  - OBJECTIVE: To evaluate the hearing status of patients being treated for pulmonary
      tuberculosis at referral hospitals in Brazil. METHODS: This was a descriptive
      study involving 97 male and female inpatients/outpatients between 18 and 60 years
      of age who were undergoing treatment for active pulmonary tuberculosis at one of
      two referral hospitals in the state of Rio de Janeiro. After being interviewed,
      all of the patients underwent pure tone audiometry. RESULTS: Of the 97 patients
      studied, 65 (67%) were male, 52 (54%) were receiving first-line treatment, and 45
      (46%) were receiving second-line treatment, which included aminoglycosides.
      Smoking, alcohol consumption, exposure to noise, and ototoxic medication use were
      identified in 65 (67%), 51 (53%), 53 (55%), and 45 (46.4%) of the patients,
      respectively. The most common auditory and vestibular complaints were dizziness,
      in 28 patients (28.8%); tinnitus, in 27 (27.8%); and hypoacusis, in 23 (23.7%).
      CONCLUSIONS: Due to the great number of patients with hearing loss in the present
      study, we recommend that all patients under tuberculosis treatment be submitted
      to auditory monitoring.

PMID- 22407045
TI  - Predictors of tuberculosis treatment outcomes.
AB  - OBJECTIVE: To analyze tuberculosis treatment outcomes and their predictors.
      METHODS: This was a retrospective longitudinal cohort study involving
      tuberculosis patients treated between 2004 and 2006 at the Instituto de Pesquisa
      Evandro Chagas, in the city of Rio de Janeiro. We estimated adjusted risk ratios
      (ARRs) for the predictors of treatment outcomes. RESULTS: Among 311 patients
      evaluated, the rates of cure, treatment abandonment, treatment failure, and
      mortality were 72%, 19%, 2%, and 6%, respectively. Changes in the treatment
      regimen due to adverse events occurred in 8%. The factors found to reduce the
      probability of cure were alcoholism (ARR, 0.30), use of the
      streptomycin+ethambutol+ofloxacin (SEO) regimen (ARR, 0.32), HIV infection
      without the use of antiretroviral therapy (ART; ARR, 0.36), and use of the
      rifampin+isoniazid+pyrazinamide+ethambutol regimen (ARR, 0.58). Being younger and
      being alcoholic both increased the probability of abandonment (ARR, 3.84 and
      1.76, respectively). It was impossible to determine the ARR for the remaining
      outcomes due to their low prevalence. However, using the relative risk (RR), we
      identified the following potential predictors of mortality: use of the SEO
      regimen (RR, 11.43); HIV infection without ART (RR, 9.64); disseminated
      tuberculosis (RR, 9.09); lack of bacteriological confirmation (RR, 4.00);
      diabetes mellitus (RR, 3.94); and homosexual/bisexual behavior (RR, 2.97). Low
      income was a potential predictor of treatment failure (RR, 11.70), whereas
      disseminated tuberculosis and HIV infection with ART were potential predictors of
      changes in the regimen due to adverse events (RR, 3.57 and 2.46, respectively).
      CONCLUSIONS: The SEO regimen should not be used for extended periods. The data
      confirm the importance of ART and suggest the need to use it early.

PMID- 22407046
TI  - Low tidal volume mechanical ventilation and oxidative stress in healthy mouse
      lungs.
AB  - OBJECTIVE: Mechanical ventilation (MV) itself can directly contribute to lung
      injury. Therefore, the aim of the present study was to investigate early
      biomarkers concerning oxidant/antioxidant balance, oxidative stress, and
      inflammation caused by short-term MV in healthy mouse lungs. METHODS: Twenty male
      C57BL/6 mice were randomly divided into two groups: MV, submitted to low tidal
      volume (V T, 6 mL/kg) MV for 30 min; and spontaneous respiration (SR), used as
      controls. Lung homogenate samples were tested regarding the activity of various
      antioxidant enzymes, lipid peroxidation, and TNF-alpha expression. RESULTS: In
      comparison with the SR group, the MV group showed a significant decrease in the
      activity of superoxide dismutase (~35%; p < 0.05), together with an increase in
      the activity of catalase (40%; p < 0.01), glutathione peroxidase (500%; p <
      0.001), and myeloperoxidase (260%; p < 0.001), as well as a reduction in the
      glutathione/oxidized glutathione ratio (~50%; p < 0.05) and an increase in TNF
      alpha expression in the MV group. Oxidative damage, assessed by lipid
      peroxidation, was also greater in the MV group (45%; p < 0.05). CONCLUSIONS: Our
      results show that short-term low V T MV can directly contribute to lung injury,
      generating oxidative stress and inflammation in healthy mouse lungs.

PMID- 22407047
TI  - Magnetic resonance of the lung: a step forward in the study of lung disease.
AB  - Magnetic resonance imaging (MRI) of the lung has progressed tremendously in
      recent years. Because of improvements in speed and image quality, MRI is now
      ready for routine clinical use. The main advantage of MRI of the lung is its
      unique combination of structural and functional assessment in a single imaging
      session. We review the three major clinical indications for MRI of the lung:
      staging of lung tumors; evaluation of pulmonary vascular disease; and
      investigation of pulmonary abnormalities in patients who should not be exposed to
      radiation.

PMID- 22407048
TI  - The use of step tests for the assessment of exercise capacity in healthy subjects
      and in patients with chronic lung disease.
AB  - Step tests are typically used to assess exercise capacity. Given the diversity of
      step tests, the aim of this review was to describe the protocols that have been
      used in healthy subjects and in patients with chronic lung disease. Step tests
      for use in healthy subjects have undergone a number of modifications over the
      years. In most step tests, the duration is variable (90 s-10 min), but the step
      height (23.0-50.8 cm) and stepping rate (22.5-35.0 steps/min) remain constant
      throughout the test. However, the use of a fixed step height and constant
      stepping rate might not provide adequate work intensity for subjects with
      different levels of fitness, the workload therefore being above or below
      individual capacity. Consequently, step test protocols have been modified by
      introducing changes in step heights and stepping rates during the test. Step
      tests have been used in patients with chronic lung diseases since the late 1970s.
      The protocols are quite varied, with adjustments in step height (15-30 cm),
      pacing (self-paced or externally paced), and test duration (90 s-10 min).
      However, the diversity of step test protocols and the variety of outcomes studied
      preclude the determination of the best protocol for use in individuals with
      chronic lung disease. Shorter protocols with a high stepping rate would seem to
      be more appropriate for assessing exercise-related oxygen desaturation in chronic
      lung disease. Symptom-limited testing would be more appropriate for evaluating
      exercise tolerance. There is a need for studies comparing different step test
      protocols, in terms of their reliability, validity, and ability to quantify
      responses to interventions, especially in individuals with lung disease.

PMID- 22407050
TI  - Carcinoid tumor and pulmonary sequestration.
AB  - Pulmonary sequestration is defined as a mass of lung tissue separated from the
      tracheobronchial tree and irrigated by an anomalous systemic artery. It is rarely
      seen in conjunction with lung neoplasms. We report the case of a 39-year-old
      female patient diagnosed with a carcinoid tumor, located in the intermediate
      bronchus and accompanied by bronchiectasis in the right lower lobe. The patient
      underwent thoracotomy for the resection of the affected area. During surgery, she
      presented with significant hemorrhage resulting from the transection of the
      anomalous artery that irrigated an intralobar pulmonary sequestration, which was
      located in right lower lobe and had not been identified in pre-operative
      examinations.

PMID- 22407049
TI  - Aspergillus fumigatus fungus ball in the pleural cavity.
AB  - OBJECTIVE: To report the cases of 6 patients with fungus ball caused by
      Aspergillus fumigatus (aspergilloma) in the pleural cavity. METHODS: Between 1980
      and 2009, 391 patients were diagnosed with aspergilloma at the Santa Casa
      Hospital Complex in Porto Alegre, Brazil. The diagnosis of aspergilloma in the
      pleural cavity was made through imaging tests revealing effusion and pleural
      thickening with air-fluid level; direct mycological examination revealing septate
      hyphae, consistent with Aspergillus sp.; and positive culture for A. fumigatus in
      the surgical specimen from the pleural cavity. RESULTS: Of the 391 patients
      studied, 6 (2%) met the established diagnostic criteria. The mean age of those 6
      patients was 48 years (range, 29-66 years), and 5 (83%) were male. The most
      common complaints were cough, expectoration, and hemoptysis. Four patients (67%)
      had a history of tuberculosis that had been clinically cured. All of the patients
      were submitted to surgical removal of the aspergilloma, followed by intrapleural
      instillation of amphotericin B, in 4; and 2 received systemic antifungal
      treatment p.o. There was clinical improvement in 5 patients, and 1 died after the
      surgery. CONCLUSIONS: In adult patients with a history of cavitary lung disease
      or pleural fistula, a careful investigation should be carried out and fungal
      infection, especially aspergilloma, should be taken into consideration. In such
      cases, laboratory testing represents the most efficient use of the resources
      available to elucidate the diagnosis.

PMID- 22407051
TI  - Subglottic cyst: a rare cause of laryngeal stridor.

PMID- 22407052
TI  - Protective ventilation and alveolar recruitment maneuver in a patient with
      leptospirosis-induced acute respiratory distress syndrome.

PMID- 22407053
TI  - Sickle cell anemia: a significant potential cause of pulmonary hypertension in
      Brazil.

PMID- 22407054
TI  - The psychophysiology of narrower face processing in autism spectrum conditions.
AB  - Faces are encountered across a huge range of visual conditions, including
      differences in light, distance and visibility. To accurately detect all faces
      under all these conditions, the face detection system must be suitably
      generalized. However, in autism spectrum conditions (ASCs), the typical
      generalization of perceptual learning is narrower. Here, we tested the
      generalization of the face detection system in a sample of adults with ASCs and a
      matched control group without ASCs. We recorded electroencephalography while
      participants viewed images of actual faces, face-like objects and non-face-like
      objects. Analysis of the N170 event-related potential component, which is related
      to the early stages of face detection, showed that the two participant groups
      were comparable in the activation of the N170 to actual faces and face-like
      objects, but that the typical control group showed an increased N170 for non-face
      like objects over the group with ASCs. This indicates that the face detection
      system is less generalized (narrower) in ASCs than in typical development. We
      propose that the reduced social interest characteristic of ASCs is associated
      with a narrower face detection system that is less reliable in detecting all the
      faces in the environment.

PMID- 22407055
TI  - The temporal change in the cortical activations due to salty and sweet tastes in
      humans:  fMRI and time-intensity sensory evaluation.
AB  - It remains unclear how the cerebral cortex of humans perceives taste temporally,
      and whether or not such objective data about the brain show a correlation with
      the current widely used conventional methods of taste-intensity sensory
      evaluation. The aim of this study was to investigate the difference in the time
      intensity profile between salty and sweet tastes in the human brain. The time
      intensity profiles of functional MRI (fMRI) data of the human taste cortex were
      analyzed using finite impulse response analysis for a direct interpretation in
      terms of the peristimulus time signal. Also, time-intensity sensory evaluations
      for tastes were performed under the same condition as fMRI to confirm the
      reliability of the temporal profile in the fMRI data. The time-intensity profile
      for the brain activations due to a salty taste changed more rapidly than those
      due to a sweet taste in the human brain cortex and was also similar to the time
      intensity sensory evaluation, confirming the reliability of the temporal profile
      of the fMRI data. In conclusion, the time-intensity profile using finite impulse
      response analysis for fMRI data showed that there was a temporal difference in
      the neural responses between salty and sweet tastes over a given period of time.
      This indicates that there might be taste-specific temporal profiles of
      activations in the human brain.

PMID- 22407056
TI  - Development of a bacterial artificial chromosome (BAC) recombineering procedure
      using galK-untranslated region (UTR) for the mutation of diploid genes.
AB  - Bacterial artificial chromosome (BAC) recombineering using galK selection allows
      DNA cloned in Escherichia coli to be modified without introducing an unwanted
      selectable marker at the modification site. Genomes of some herpesviruses have a
      pair of inverted repeat sequences that makes it very difficult to introduce
      mutations into diploid (duplicate) genes using the galK selection method. To
      mutate diploid genes, we developed a galK-UTR BAC recombineering procedure that
      blocks one copy of the target diploid gene by insertion of a galK untranslated
      region (UTR), which enables the simple mutation of the other copy. The blocked
      copy can then be replaced with an UTR-specific primer pair. The IR2 gene of
      equine herpesvirus 1 (EHV-1) maps within both the internal (IR) and terminal
      repeat (TR) of the genomic short region and is expressed at low levels because
      its promoter is TATA-less. Both IR2 promoters in EHV-1 BAC were replaced with a
      mutant IR2 promoter containing three Sp1-binding motifs and a consensus TATA box
      by galK-UTR BAC recombineering. The expression level of the IR2 protein
      controlled by the modified promoter increased approximately 4-fold as compared to
      that of wild-type EHV-1. The galK-UTR method will provide a useful tool in
      studies of herpesviruses.

PMID- 22407057
TI  - Three-hour interval drain clamping reduces postoperative bleeding in total knee
      arthroplasty: a prospective randomized controlled trial.
AB  - BACKGROUND: Total knee arthroplasty (TKA) is a common procedure that has a risk
      of significant blood loss and blood transfusion, and carries a substantial risk
      for immunologic reactions and disease transmission. Drain clamping is a popular
      method that is applied to reduce blood loss after TKA. However, the clamping
      protocol remains controversial. Therefore, we established a new protocol, 3-h
      interval clamping, and compared the bleeding control efficacy of this protocol
      following TKA with the non-clamping technique. METHODS: Between March and July
      2008, we enrolled 100 patients (100 knees) who underwent uncomplicated TKA using
      a minimally invasive surgical technique. The patients were randomly assigned into
      two groups based on the draining protocol: non-clamping (group A) and 3-h
      interval clamping (group B). For group A, a vacuum drain was connected to a
      container and was run continuously during the first postoperative day, whereas
      the vacuum was stopped twice (for ~3 h each time) for group B. Demographic
      characteristics and clinical data were collected, including the levels of
      hemoglobin and hematocrit, the total blood loss volume, the number of patients
      who required a blood transfusion, and any complications that developed. The
      perioperative data were compared between the two groups. RESULTS: The drainage
      blood volume in the interval-clamping group (group B) was significantly lower
      than that in the non-clamping group (group A) during the first 48 h following the
      procedure (p < 0.001 and p = 0.005 for first and second postoperative days,
      respectively). The mean fall in hemoglobin levels at 12 h in the interval
      clamping group (2.8 +/- 0.9 g/dL) was also lower than in the non-clamping group
      (3.2 +/- 0.8 g/dL). In the 3-h interval clamping protocol, the number of patients
      requiring a transfusion was 2.2 times less than the number in the non-clamping
      protocol, but was not significantly different (odds ratio = 2.20, p = 0.24), and
      the significant predictor of blood transfusion was the preoperative hemoglobin
      level (odds ratio = 7.73, p < 0.001). No wound infection or clinical venous
      thromboembolisms were detected in our study. CONCLUSION: The 3-h interval
      clamping is a newly developed protocol for reducing blood loss after TKA. The
      protocol lessens the decrease in postoperative hemoglobin levels. This protocol
      can be applied easily without increasing clinical thromboembolic events and wound
      complications.

PMID- 22407058
TI  - Tissue Banking and Transfusion Medicine - a Suitable Cooperation Model.

PMID- 22407059
TI  - Lenalidomide-induced elevated bilirubin.
AB  - Lenalidomide is an immunomodulator used to treat 5q-myelodysplastic syndrome,
      myelofibrosis, and multiple myeloma. We describe a 55-year-old male who was
      started on lenalidomide 10 mg daily for 21 days followed by 7 days off therapy
      for the treatment of early stage post-polycythemia vera myelofibrosis. Following
      initiation of lenalidomide, the patient was noted to have an asymptomatic
      increase in unconjugated bilirubin. Alkaline phosphatase, aspartate transaminase,
      and alanine aminotransferase were normal. During the 7 days off of lenalidomide,
      bilirubin began to trend down. Re-challenge with lenalidomide in subsequent
      cycles results in an asymptomatic elevation in unconjugated bilirubin followed by
      improvement during the 7-day lenalidomide-free period. The patient is a
      heterozygote for the TA7 allele which can decrease expression of uridine
      diphosphate glycuronosyl transferase 1A1, the enzyme responsible for conjugation
      of bilirubin. Therapy with lenalidomide may have unmasked Gilbert's syndrome in
      the patient.

PMID- 22407060
TI  - Expression of miR-133 and miR-30 in chronic atrial fibrillation in canines.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The
      most significant histological property of AF is atrial fibrosis, but the
      underlying mechanism is not clear. In this study we investigated the expression
      of miR-133 and miR-30, anti-fibrotic microRNAs (miRNAs), in chronic AF in
      canines. A total amount of 42 mongrel canines of either gender, weighing between
      20 and 28 kg, were randomly assigned to the sham-operated and AF groups. All
      canines were subjected to weekly physical examinations and electrocardiogram.
      Alterations in tissue structure were assessed in atrial tissue samples by using
      hematoxylin and eosin and Masson's trichrome. The expression of miR-133 and miR
      30 was determined by TaqMan real-time polymerase chain reaction (RT-PCR) and
      northern blot analyses of atrial tissue. The data were analyzed using the program
      SPSS 11.5 for Windows. At follow-up, rapid pacing from the left superior
      pulmonary vein induced sustained AF in the AF group. In the left atrium,
      increased interstitial fibrosis and chronic inflammation were observed. RT-PCR
      and northern blot analyses showed that miR-133 and miR-30 expression was
      downregulated in the AF group. Our results show that both miR-133 and miR-30 play
      an important role in controlling structural changes in chronic AF.

PMID- 22407061
TI  - Lupus erythematosus panniculitis treated with tacrolimus.

PMID- 22407062
TI  - Nitrogen, phosphorus and light effects on growth and allocation of biomass and
      nutrients in wild rice.
AB  - Separating plastic from ontogenetic and growth-limiting responses of plants to
      changes in resource availability can be challenging because there are a total of
      eight combinations of these three types of responses. These can, however, be
      uniquely distinguished on plots of root:shoot ratios against total biomass
      through time. We used this approach to separate ontogenetic, plastic, and growth
      limiting responses of wild rice (Zizania palustris L.) to changes in nitrogen,
      phosphorus, and light availabilities. Relative growth rate was limited primarily
      by nitrogen but responded to increased light and phosphorus after nitrogen
      limitations were alleviated. Nitrogen addition increased relative growth rate
      because it simultaneously increased unit leaf rate, specific leaf area, and leaf
      weight ratio. Increased light did not change relative growth rate because
      decreased specific leaf area and leaf weight ratio compensated the increased unit
      leaf rate. Phosphorus did not change either relative growth rate or its
      underlying components. Plants responded ontogenetically to increased nitrogen and
      light availabilities by accelerating their developmental rate, and plastically by
      decreasing or increasing their root:shoot ratios, respectively. Plants did not
      respond either ontogenetically or plastically to increased phosphorus
      availability. Ontogenetic changes in growth can be separated from plastic and
      growth-limiting responses by plotting root:shoot ratio against total biomass in
      the context of the eight possible responses identified above, and also by
      examining how the underlying components of relative growth rate respond.

PMID- 22407063
TI  - How is the VS (vessel plus surface) classification system applicable to
      magnifying narrow-band imaging examinations of gastric neoplasias initially
      diagnosed as low-grade adenomas?

PMID- 22407064
TI  - Can magnifying endoscopy with narrow band imaging be useful for low grade
      adenomas in preoperative biopsy specimens?
AB  - BACKGROUND: In biopsy specimens with low grade adenomas, it is often difficult to
      identify the presence of high grade adenomas or early carcinomas and low grade
      adenomas preoperatively, and clear guidelines have not yet been defined for the
      applicability of endoscopic treatment to low grade adenomas identified in biopsy
      specimens. METHODS: We aimed to clarify the usefulness of magnifying endoscopy
      with narrow band imaging (NBI) compared to conventional white light endoscopy for
      diagnosing actual high grade adenomas or early carcinomas with low grade
      adenomas, using the VS (microvascular pattern [V] and microsurface pattern [S])
      classification for low grade adenomas in biopsy specimens. The study cohort
      consisted of 135 patients who were diagnosed with low grade adenomas in
      preoperative biopsy specimens and received endoscopic submucosal dissection.
      RESULTS: In the elevated type of lesion, magnifying endoscopy with NBI diagnosed
      high grade adenomas or early carcinomas at a higher sensitivity and specificity
      than conventional white light endoscopy (82.4 vs. 70.6%, P = 0.391, 97.3 vs.
      54.7%, P < 0.0001). In the depressed macroscopic type of lesion, magnifying
      endoscopy with NBI also diagnosed high grade adenomas or early carcinomas at a
      higher sensitivity (95.5 vs. 68.2%, P = 0.0459) than conventional white light
      endoscopy. Although the specificity was high, at 100%, the difference when
      compared to conventional white light endoscopy was not significant (100 vs. 100%,
      P > 0.99). CONCLUSIONS: For low grade adenomas in biopsy specimens, it is vital
      to take sufficient consideration of endoscopic findings and not take action based
      only on the biopsy results. If a decision is made using the VS classification
      with magnifying endoscopy with NBI, actual high grade adenomas or early
      carcinomas can be differentiated from low grade adenomas so that endoscopic
      treatment can be performed more strictly.

PMID- 22407065
TI  - Phase transitions and incommensurability in the layered semiconductor TlInS2--an
      NMR study.
AB  - We report on the first NMR study of powder and single crystal samples of thallium
      indium sulfide, TlInS(2). The crystal under study is a pure single-layer TlInS(2)
      polytype. Our findings show that transformation from the high temperature
      paraelectric phase to the low temperature ferroelectric phase occurs via an
      incommensurate phase that exists in the temperature range from T(c) = 192 K to
      T(i) = 205 K. On approaching the phase transition at T(i) from above, the crystal
      exhibits a soft mode behavior. A discrepancy in the literature data on the phase
      transitions in TlInS(2) is discussed and ascribed to polytypism of the TlInS(2)
      crystals.

PMID- 22407066
TI  - Gnathostomiasis and sushi ingestion.

PMID- 22407067
TI  - Infundibular (follicular) and infundibulocystic squamous cell carcinoma:  a
      clinicopathological and immunohistochemical study.

PMID- 22407068
TI  - "Onycholemmal carcinoma." An unusual case with apocrine and sebaceous
      differentiation. Are these tumors a microcystic nail bed carcinoma?
AB  - Subungual malignant epithelial tumors with tricholemmal keratinization have
      rarely been described as "malignant proliferating onycholemmal cyst" and
      "onycholemmal carcinoma (OC)." We report an additional case of a slow growing OC
      occurring on the middle finger of a 58-year-old man, which was unusual as it
      showed sebaceous-apocrine differentiation, in addition to a nail bed carcinoma
      with tricholemmal microcysts. We therefore consider the descriptive term of
      microcystic nail bed carcinoma more appropriate than OC. It is recognized that
      none of the rare cases of OC meet the classical additional criteria proposed by
      Headington for tricholemmal carcinoma, that is, lobular arrangement, peripheral
      palisading, thickened basement membrane, and glycogen-positive tumors cells. On
      the other hand, we suggest that the term follicular microcysts of the nail bed
      should be retained to describe the true nature of subungual epidermoid
      inclusions, which show usually a limited differentiation toward the follicular
      isthmus. Therefore, the previous cases of OC without sebaceous-apocrine
      differentiation could be best classified as a microcystic nail bed carcinoma
      arising from the follicular microcysts of the nail bed, with a limited
      differentiation toward the keratinization of the follicular isthmus.

PMID- 22407069
TI  - Anogenital sweat gland adenocarcinoma of the vulva:  a diagnostic conundrum.

PMID- 22407070
TI  - Mapping Toll-like receptor activity in different stages of cutaneous T-cell
      lymphoma.
AB  - It is known that human keratinocytes (KCs) express Toll-like receptors (TLRs).
      However, published reports conflict regarding TLR expression in cutaneous T-cell
      lymphoma patient's KCs. To define the pattern of expression and detect any
      differences of TLRs 1-9 and p65 expression in epidermal KCs, tumor infiltrate,
      and endothelial cell types using immunohistochemical stains on fixed and paraffin
      embedded sections of mycosis fungoides (MF) in patch, plaque, and nodular stages.
      MF cases showed no change in pattern of TLRs expressed through different stages
      but increased epidermal staining of TLRs 2, 3, 4, 5, 6, and 8 with higher scores
      associated with more aggressive stages. Endothelial cell staining was increased
      for TLR 4 and 6. Tumor infiltrate staining was strongest with TLRs 5 and 7.
      Individual cases with disease progression showed increased intensity of TLRs 4,
      5, and 6 staining in the epidermis, tumor infiltrate, and endothelial cell. p65
      verified nuclear factor kappa B activation of the TLR pathway with trace staining
      of the epidermis and 1-2+ staining of tumor infiltrate. MF cases showed increased
      epidermal expression of TLRs and increased endothelial cell staining compared
      with controls. TLR expression may be driven by antigenic stimulation and may play
      a role in the activation of neoplastic T cells in the skin. Further definition of
      TLR patterns may refine the use of TLR modifiers for treatment.

PMID- 22407071
TI  - Transient inhibition of the dorsolateral prefrontal cortex disrupts somatosensory
      modulation during standing balance as measured by electroencephalography.
AB  - Several studies have shown that a light fingertip touch on a stable surface
      reduces body sway for individuals standing with their eyes closed even when touch
      forces are too low to offer mechanical support. It has been proposed that this is
      due to the availability of sway-relevant sensory feedback from the hand
      compensating for lost vision. Recently, we revealed modulation of cortical
      sensory transmission of information from the hand depending on the task (e.g.
      relevant or not relevant to balance control). Of interest in the present study is
      the potential origin of task-specific modulation of cortically evoked sensory
      potentials linked to balance control. We aimed to investigate the role of the
      prefrontal cortex by temporarily suppressing this region and observing
      differences in cortical events. Continuous theta-burst stimulation was applied to
      either the prefrontal cortex or a control stimulation site before balance
      testing. During balance testing, individuals stood in tandem on a force plate
      with their eyes closed while lightly touching a stable surface or a sway
      referenced surface with the index finger. Throughout testing, the median nerve
      was stimulated and electroencephalography was used to measure somatosensory
      evoked potentials. As expected, the availability of stable light touch reduced
      the medial-lateral centre of pressure sway. Importantly, in the present study,
      there was a loss of task-related P200 modulation at FCZ following stimulation of
      the prefrontal cortex. The present findings support the hypothesis that the
      prefrontal cortex may serve to regulate task-related sensory reweighting of
      haptic information that may be used during the control of standing balance.

PMID- 22407072
TI  - Failure of percutaneous remodeling of the ligamentum flavum and lamina for
      neurogenic claudication.
AB  - BACKGROUND: Percutaneous remodeling of the ligamentum flavum and lamina (PRLL),
      commercially known as minimally invasive lumbar decompression (mild technique),
      relies on fluoroscopy and epidural contrast to direct surgical instruments via a
      6-mm cannula. OBJECTIVE: To evaluate the safety and efficacy of PRLL and present,
      to our knowledge, the first reported imaging findings after PRLL. METHODS: We
      performed a prospective study of PRLL for neurogenic claudication. Primary
      outcomes were Oswestry Disability Index, Short-Form 12 version 2.0 health survey,
      and visual analog scale for pain at 26 weeks. Analgesic use was also assessed.
      Postoperative magnetic resonance imaging was performed at 12 weeks. Long-term
      failure, defined as the poststudy need for secondary surgery, was assessed up to
      18 months. RESULTS: Ten subjects with an average age of 64 years (range, 41-81
      years) were treated between September 2008 and January 2009. There were no major
      adverse events. Mean postoperative visual analog scale score remained
      significantly reduced throughout 26 weeks (P =.015, analysis of variance). Mean
      postoperative Oswestry Disability Index was also improved by 1 week and remained
      significant throughout 26 weeks (P = .024; analysis of variance). However, there
      was a trend toward increased reliance on narcotic type medications
      postoperatively. Imaging studies did not show significant decompression of the
      spinal canal in any patient. In the poststudy period, recurrent claudication
      requiring laminectomy developed in 6 patients (60%). CONCLUSION: Throughout 26
      weeks, pain and disability scores were decreased; however, PRLL did not improve
      the degree of stenosis on imaging studies. Although PRLL appears to be safe in
      this small cohort of patients, poststudy outcomes indicate that the failure rate
      is unacceptably high.

PMID- 22407073
TI  - Effects of mobile and digital support for a structured, competency-based
      curriculum in neurosurgery residency education.
AB  - BACKGROUND: Changes in neurosurgical practice and graduate medical education
      impose new challenges for training programs. OBJECTIVE: We present our experience
      providing neurosurgical residents with digital and mobile educational resources
      in support of the departmental academic activities. METHODS: A weekly mandatory
      conference program for all clinical residents based on the Accreditation Council
      for Graduate Medical Education competencies, held in protected time, was
      introduced. Topics were taught through didactic sessions and case discussions.
      Faculty and residents prepare high-quality presentations, equivalent to peer
      review leading papers or case reports. Presentations are videorecorded, stored in
      a digital library, and broadcasted through our Website and iTunes U. Residents
      received mobile tablet devices with remote access to the digital library,
      applications for document/video management, and interactive teaching tools.
      RESULTS: Residents responded to an anonymous survey, and performances on the Self
      Assessment in Neurological Surgery examination before and after the intervention
      were compared. Ninety-two percent reported increased time used to study outside
      the hospital and attributed the habit change to the introduction of mobile
      devices; 67% used the electronic tablets as the primary tool to access the
      digital library, followed by 17% hospital computers, 8% home computers, and 8%
      personal laptops. Forty-two percent have submitted operative videos, cases, and
      documents to the library. One year after introducing the program, results of the
      Congress of Neurological Surgeons-Self-Assessment in Neurological Surgery
      examination showed a statistically significant improvement in global scoring and
      improvement in 16 of the 18 individual areas evaluated, 6 of which reached
      statistical significance. CONCLUSION: A structured, competency-based
      neurosurgical education program supported with digital and mobile resources
      improved reading habits among residents and performance on the Congress of
      Neurological Surgeons-Self-Assessment in Neurological Surgery examination.

PMID- 22407074
TI  - Short-term complications associated with surgery for high-grade spondylolisthesis
      in adults and pediatric patients: a report from the scoliosis research society
      morbidity and mortality database.
AB  - BACKGROUND: Although it is generally agreed upon that surgery for high-grade
      spondylolisthesis (HGS) is associated with more complications than low-grade
      spondylolisthesis, its description is primarily based on case reports and
      relatively small case series. OBJECTIVE: To assess short-term complication rates
      associated with the surgical treatment of HGS in pediatric and adult patients and
      to identify factors associated with increased complication rates. METHODS: All
      cases of HGS from the Scoliosis Research Society Morbidity and Mortality database
      for the year 2007 were reviewed. Patients were classified as pediatric (<=18
      years) or adult (>18 years). Complications were tabulated, and the rates were
      compared between the patient groups and based on clinical and surgical factors.
      RESULTS: 165 cases of HGS were reported (88 pediatric, 77 adult). There were 49
      complications (29.7%) in 41 patients (24.8%), with no difference in the
      proportions of pediatric vs adult patients with a complication (P = .86).
      Occurrence of new neurological deficit after surgery was the most common
      complication, seen in 19 (11.5%) patients. Performance of an osteotomy was
      associated with a higher incidence of new neurological deficits in both adult and
      pediatric groups (P = .02 and P = .012, respectively). Although most of the new
      neurological deficits improved over follow-up, 10% had no improvement.
      CONCLUSION: This study provides short-term complication rates associated with
      surgical treatment for HGS in adult and pediatric patients and may prove valuable
      for patient counseling, surgical planning, and in efforts to improve the safety
      of patient care.

PMID- 22407075
TI  - What patients with gilles de la tourette syndrome should be treated with deep
      brain stimulation and what is the best target?
AB  - BACKGROUND: Gilles de la Tourette syndrome (GTS) is a chronic neurodevelopmental
      disorder characterized by tics and associated behavioral symptoms. Over the past
      decade, deep brain stimulation (DBS) has been increasingly advocated as a
      reversible and controllable procedure for selected cases of GTS. OBJECTIVE: We
      set out to answer 2 clinically relevant questions: what patients with GTS should
      be treated with DBS and what is the best target? METHODS: We conducted a
      systematic literature review of the published studies of DBS in GTS and
      critically evaluated the current evidence for both patient and target selection.
      RESULTS: Since 1999, up to 99 cases of DBS in GTS have been reported in the
      scientific literature, with varying selection criteria, stimulation targets, and
      assessment protocols. The vast majority of studies published to date are case
      reports or case series reporting successful outcomes in terms of both tic
      severity improvement and tolerability. The reviewed studies suggest that the best
      candidates are patients with significant functional impairment related to the tic
      symptoms, who did not respond to conventional pharmacological and behavioral
      interventions. The globus pallidus internus and thalamus appear to be the safest
      and most effective targets, especially for patients with "pure" GTS and patients
      with comorbid obsessive-compulsive symptoms, anxiety, and depression. CONCLUSION:
      DBS is a promising treatment option for severe cases of GTS. There is a need to
      reach consensus on the definition of "treatment-refractoriness" and to conduct
      larger double-blind randomized controlled studies on the most promising targets.

PMID- 22407076
TI  - Protein profiling of keloidal scar tissue.
AB  - Clinically, keloids are defined as scars that invade adjacent healthy tissue and
      are caused by tissue injury; however, the clear distinction relating keloids to
      wound healing or to cancer remains elusive. This study profiled protein extracts
      from the regions of keloid tissues to determine the activities within these
      different zones, and to help underpin the activities apparent within different
      regions of the disease. Two-dimensional gel electrophoresis, liquid
      chromatography mass spectrometer (LCMS) and a Mascot online database search were
      employed for comparative proteomic analysis between four sites in keloidal scars
      (KS). Out of 400 spots identified in all gels, 21 were unique to given KS sites.
      These were identified using LCMS and the results showed the presence of
      mitochondrial and structural proteins in the margin, while the top contained
      keratin II. Heat shock protein was the only protein present in the internal
      normal control and margin, while the external normal contain keratin II and the
      voltage-dependent anion-selective channel protein, annexin A6, plus glial
      fibrillary acidic protein. This work is novel since it has identified
      differentially expressed proteins across the tested keloidal scar sites. The
      presence of mitochondrial-associated proteins at the margins suggests that this
      is the most active part of the scar.

PMID- 22407077
TI  - Identification of fibrocytes from mesenchymal stem cells in keloid tissue: a
      potential source of abnormal fibroblasts in keloid scarring.
AB  - Abnormal fibroblasts have been implicated in keloid formation, a benign but
      fibroproliferative skin disorder. However, the exact source of these cells
      remains unknown. Fibrocytes are considered to be hybrid mesenchymal/hematopoietic
      cells, having been identified in various fibrotic disorders as the precursors of
      fibroblasts. Therefore, we hypothesized that a population of fibrocytes is
      present in keloid tissue as opposed to the mesenchymal stem cells (MSCs). We
      compared the proportion of MSCs in keloid versus bone marrow-derived cells and
      compared fibrocytes in keloid as opposed to normal scar tissue. We also
      investigated the propagation of fibrocytes in serum-supplemented versus serum
      free media. Using multicolor fluorescence-activated cell analysis, we found
      distinct populations of MSCs (CD34(-)CD73(+)CD90(+)CD105(+)) that were different
      from CD45RO(+)25F9(+)MRP8/14(+) fibrocytes present in keloid tissue, while very
      few fibrocytes were observed in normal scar tissue. The proportion of keloid
      derived cells in serum-free or serum-supplemented cultures expressing these
      fibrocyte markers was greater than from cultures derived from normal scar tissue
      (p < 0.05). We found that the proliferation of CD45(+)/Col1(+) keloid cells in
      vitro was greater in serum-free media compared to serum-supplemented media. This
      is the first study to have identified fibrocytes isolated from keloid tissue and
      normal scars, utilizing a specific set of markers for fibrocytes. This finding
      may aid our understanding of the origin of abnormal fibroblasts identified in
      keloid scarring. The identification of fibrocyte populations distinct from MSCs
      in keloid scar tissue could lead to novel targets for therapeutic intervention,
      treatment and prevention of recurrence.

PMID- 22407078
TI  - Reverse thioether ligation route to multimeric peptide antigens.
AB  - Multimeric presentation, a rather effective way of enhancing peptide
      immunogenicity, is best exemplified by MAP (multiple antigenic peptide)
      dendrimers consisting of a branched Lys core on which several copies of the
      peptide epitope are displayed. While accessible by solid-phase synthesis, MAPs
      can also be conveniently made in solution, e.g., by linking the epitope (N
      acetylated and with a C-terminal Cys) through a thioether bond onto the alpha and
      epsilon (haloacetyl-activated) positions of the Lys core. We now report the
      reverse version of this approach, whereby a chloroacetyl-derivatised epitope is
      tethered to a thiol-functionalised form of a Lys dendron core. This convergent
      approach can be carried out either in solution or in the solid phase and is
      advantageous because (i) in situ tris(2-carboxyethyl)phosphine (TCEP)-mediated
      reduction of disulfide bonds maintains the thiol platform reactive throughout the
      ligation process; (ii) the low amounts of TCEP used pose minimal risk to
      chloroacetyl groups in the peptide, resulting in (iii) significantly reduced
      byproduct formation, hence cleaner products. For the solid phase version of the
      method, an optimised procedure has been devised to convert the Lys core into a
      tetrathiol dendron.

PMID- 22407079
TI  - A new perspective on anhedonia in schizophrenia.
AB  - OBJECTIVE: Previous research provides evidence for discrepancies in various types
      of emotional self-report in individuals with schizophrenia; patients and healthy
      subjects report similar levels of positive emotion when reporting current
      feelings, yet patients report lower levels of positive emotion when reporting on
      noncurrent feelings. Such apparent discrepancies, which have come to be termed
      the "emotion paradox" in schizophrenia, have complicated our understanding of
      what anhedonia actually reflects in this patient population. The authors sought
      to resolve this paradox. METHOD: The authors reviewed the empirical literature on
      anhedonia and emotional experience in schizophrenia through the lens of the
      accessibility model of emotional self-report, a well-validated model of emotional
      self-report developed in the affective science literature that clarifies the
      sources of emotion knowledge that individuals access when providing different
      types of self-report. The authors used this model to propose a resolution to the
      "emotion paradox" and to provide a new psychological conceptualization of
      anhedonia. RESULTS: Data are presented in support of this new perspective on
      anhedonia and to demonstrate how cognitive impairments may influence reports of
      noncurrent feelings in schizophrenia. CONCLUSIONS: The authors conclude that
      anhedonia should no longer be considered an experiential deficit or a diminished
      "capacity" for pleasure in patients with schizophrenia. Rather, anhedonia
      reflects a set of beliefs related to low pleasure that surface when patients are
      asked to report their noncurrent feelings. Encoding and retrieval processes may
      serve to maintain these beliefs despite contrary real-world pleasurable
      experiences. Implications for assessment and treatment are discussed in relation
      to this new conceptualization of anhedonia.

PMID- 22407080
TI  - Long-term follow-up of the TIPS early detection in psychosis study: effects on 10
      year outcome.
AB  - OBJECTIVE: Early detection in first-episode psychosis confers advantages for
      negative, cognitive, and depressive symptoms after 1, 2, and 5 years, but
      longitudinal effects are unknown. The authors investigated the differences in
      symptoms and recovery after 10 years between regional health care sectors with
      and without a comprehensive program for the early detection of psychosis. METHOD:
      The authors evaluated 281 patients (early detection, N=141) 18 to 65 years old
      with a first episode of nonaffective psychosis between 1997 and 2001. Of these,
      101 patients in the early-detection area and 73 patients in the usual-detection
      area were followed up at 10 years, and the authors compared their symptoms and
      recovery. RESULTS: A significantly higher percentage of early-detection patients
      had recovered at the 10-year follow-up relative to usual-detection patients. This
      held true despite more severely ill patients dropping out of the study in the
      usual-detection area. Except for higher levels of excitative symptoms in the
      early-detection area, there were no symptom differences between the groups. Early
      detection recovery rates were higher largely because of higher employment rates
      for patients in this group. CONCLUSIONS: Early detection of first-episode
      psychosis appears to increase the chances of milder deficits and superior
      functioning. The mechanisms by which this strategy improves the long-term
      prognosis of psychosis remain speculative. Nevertheless, our findings over 10
      years may indicate that a prognostic link exists between the timing of
      intervention and outcome that deserves additional study.

PMID- 22407082
TI  - Mineralocorticoid receptor Iso/Val (rs5522) genotype moderates the association
      between previous childhood emotional neglect and amygdala reactivity.
AB  - OBJECTIVE: The amygdala is especially reactive to threatening stimuli, and the
      degree of reactivity predicts individual differences in the expression of
      depression and anxiety. Emerging research suggests that emotional neglect during
      childhood as well as hypercortisolemia may lead to heightened threat-related
      amygdala reactivity. This raises the possibility that genetic variation affecting
      hypothalamic-pituitary-adrenal (HPA) axis function contributes to individual
      differences in amygdala reactivity, both independently and as a function of
      childhood emotional neglect. METHOD: This study assessed whether the
      mineralocorticoid receptor iso/val polymorphism (rs5522), a functional genetic
      variant affecting HPA axis function, influenced threat-related amygdala
      reactivity in 279 individuals in late childhood and early adolescence. The study
      also explored the extent to which any effects of the genotype on amygdala
      reactivity were contingent upon previous childhood emotional neglect. RESULTS:
      Prior childhood emotional neglect and the val allele were associated with greater
      amygdala reactivity. Moreover, a significant genotype-by-emotional neglect
      interaction was observed whereby greater amygdala reactivity in val allele
      carriers was independent of previous childhood emotional neglect, while greater
      reactivity in iso homozygotes was revealed only in the context of a history of
      elevated emotional neglect. At relatively low levels of previous emotional
      neglect, val carriers had heightened amygdala reactivity relative to iso
      homozygotes. CONCLUSIONS: These results suggest that relatively greater amygdala
      reactivity may represent a biological mechanism through which childhood adversity
      and functional genetic variation in HPA axis responsiveness to stress may mediate
      risk for psychopathology.

PMID- 22407083
TI  - Prevention of postpartum psychosis and mania in women at high risk.
AB  - OBJECTIVE: Women with a history of bipolar disorder or postpartum psychosis are
      at extremely high risk of relapse postpartum. Although lithium prophylaxis has
      demonstrated efficacy in reducing postpartum relapse, the timing of prophylaxis
      remains controversial given the balance of risks and benefits for the mother and
      fetus. The authors compared lithium use during pregnancy to its initiation
      postpartum in women at high risk for postpartum psychosis. METHOD: Between 2003
      and 2010, 70 pregnant women at high risk for postpartum psychosis were referred
      to the authors' psychiatric outpatient clinic. Women who were initially
      medication free were advised to start lithium prophylaxis immediately postpartum.
      Women already taking maintenance lithium during pregnancy were advised to
      continue treatment. RESULTS: All women with a history of psychosis limited to the
      postpartum period (N=29) remained stable throughout pregnancy despite being
      medication free. Of the women with bipolar disorder (N=41), 24.4% relapsed during
      pregnancy, despite prophylaxis use by the majority throughout pregnancy. The
      postpartum relapse rate was highest in women with bipolar disorder who
      experienced mood episodes during pregnancy (60.0%). In contrast, none of the 20
      women with a history of postpartum psychosis only who used postpartum prophylaxis
      relapsed, compared to 44.4% of patients with postpartum psychosis only who
      declined prophylaxis. CONCLUSIONS: The authors recommend initiating prophylactic
      treatment immediately postpartum in women with a history of psychosis limited to
      the postpartum period, to avoid in utero fetal exposure to medication. Patients
      with bipolar disorder require continuous prophylaxis throughout pregnancy and the
      postpartum period to reduce peripartum relapse risk.

PMID- 22407084
TI  - Risk factors for chronic pain after open ventral hernia repair by underlay mesh
      placement.
AB  - BACKGROUND: Incisional hernia is a frequent complication following abdominal
      surgery. Repairs that include the use of mesh have been associated with decreased
      recurrence. The aim of the present study was to determine the outcomes and risk
      factors for chronic pain after ventral hernia repair with underlay placement of a
      composite polypropylene mesh. METHODS: A retrospective study was conducted from
      September 2005 to June 2008. The study included consecutive patients who
      underwent elective incisional hernia repair with underlay composite mesh
      placement. Postoperative course, recurrence, pain, and patient satisfaction were
      assessed by an independent observer. Chronic pain was defined as significant pain
      persisting after 3 months as assessed using a 10-point numeric scale (>= 3:
      chronic pain, >= 7: severe pain). RESULTS: After a mean follow-up period of 24.6
      months, 109 of 121 patients operated on during the period were evaluated. No
      patients experienced small bowel obstructions, enterocutaneous fistulas, or mesh
      infections leading to the need for mesh removal. The recurrence rate was 6.1 % at
      the repair site and 10.5% at another site. Thirty-one patients (28%) had chronic
      pain and seven patients (6.6%) had severe pain. Affective and nociceptive
      components were the majority of complaints. Chronic cough was the only variable
      independently associated with chronic pain in univariate and multivariate
      analyses (OR = 4.8; p = 0.007). CONCLUSIONS: Intraperitoneal composite mesh
      placement after ventral hernia repair is safe with regard to intra-abdominal
      potential complications. Chronic pain is not uncommon, with chronic cough
      identified as the major independent predictor.

PMID- 22407085
TI  - Prognostic nutritional index predicts outcomes of gastrectomy in the elderly.
AB  - BACKGROUND: Owing to the increased life expectancy, elderly patients with gastric
      cancer is also increasing. Onodera's prognostic nutritional index (PNI) is an
      assessment tool for nutritional status of surgical patients and possibly predicts
      prognosis of the patients. The aim of the present study is to clarify the
      predictive and prognostic significance of PNI in elderly patients who underwent
      gastrectomy for gastric cancer. METHODS: Two hundred ninety-five patients,
      including 196 nonelderly patients under 75 years old (group NE) and 99 elderly
      patients (group E), were eligible. We collected the data on nutritional status
      and the outcome of gastrectomy, including morbidity, mortality, and survival of
      these patients. A Cox proportional hazards model was used to evaluate the
      prognostic significance. RESULTS: The PNI was significantly lower in group E than
      in group NE. Both morbidity and mortality rates after gastrectomy were similar
      between the groups. Although PNI could not predict the postoperative events in
      group NE, low PNI might be a risk of mortality and morbidity in the elderly.
      Although survival after gastrectomy was similar among groups divided by the
      median PNI value (49.2) in group NE, the prognosis of PNI-L (<44.7) was
      significantly poorer than PNI-H (PNI ? 44.7) in group E. Multivariate analysis
      demonstrated that PNI-L was an independent prognostic factor in the elderly.
      CONCLUSIONS: The PNI predicts both short-term and long-term outcomes after
      gastrectomy in the elderly.

PMID- 22407086
TI  - Re: Outcome of surgery for primary hyperaldosternonism.

PMID- 22407087
TI  - Does laparoscopic appendectomy impart an advantage over open appendectomy in
      elderly patients?
AB  - BACKGROUND: The use of laparoscopy in the elderly has been increasing in recent
      years. The data comparing laparoscopic (LA) with open appendectomy (OA) in
      elderly patients are minimal. We evaluated outcomes of LA versus OA in perforated
      and nonperforated appendicitis in elderly patients (aged >= 65 years). METHODS:
      Using the Nationwide Inpatient Sample database, clinical data of elderly patients
      who underwent LA and OA for suspected acute appendicitis were evaluated from 2006
      to 2008. RESULTS: A total of 65,464 elderly patients underwent urgent
      appendectomy during this period. The rate of perforated appendicitis was twice as
      high in elderly patients (50 vs. 25%, p < 0.01) and rate of LA in elderly
      patients was lower (52 vs. 63%, p < 0.01) compared with patients younger than
      aged 65 years. Utilization of LA increased 24% from 46.5% in 2006 to 57.8% in
      2008 (p < 0.01). In elderly patients with acute nonperforated appendicitis, LA
      had lower overall complication rate (15.82 vs. 23.49%, p < 0.01), in-hospital
      mortality (0.39 vs. 1.31%, p < 0.01), hospital charges ($30,414 vs. $34,095, p <
      0.01), and mean length of stay (3.0 vs. 4.8 days, p < 0.01) compared with OA.
      Additionally, in perforated appendicitis in elderly patients, LA was associated
      with lower overall complication rate (36.27 vs. 46.92%, p < 0.01), in-hospital
      mortality (1.4 vs. 2.63%, p < 0.01), mean hospital charges ($43,339 vs. $57,943,
      p < 0.01), and shorter mean LOS (5.8 vs. 8.7 days, p < 0.01). CONCLUSIONS:
      Laparoscopic appendectomy can be performed safely with significant advantages
      compared with open appendectomy in the elderly and should be considered the
      procedure of choice for perforated and nonperforated appendicitis in these
      patients.

PMID- 22407088
TI  - Trends in surgical treatment of pilonidal sinus diseases: primary closure or
      flap?

PMID- 22407089
TI  - Cosmesis and body image after minimally invasive or open thyroid surgery.
AB  - BACKGROUND: Minimally invasive techniques, such as laparoscopic appendectomy or
      minimally invasive thyroid surgery, are thought to produce better cosmetic
      results. However, cosmesis in thyroid surgery was rarely investigated using a
      standardized approach. The objectives of this study were to evaluate body image
      and cosmesis in patients who had either minimally invasive (MI) or conventional
      open (CO) thyroid surgery. METHODS: Two hundred fifty patients of 540
      participated (46.3 %): 50 patients (20.0 %) had MI thyroid surgery and 200 (80.0
      %) had CO thyroid surgery. The patients filled out a body image questionnaire
      that investigated body image, cosmesis, and self-confidence. SPSS 19.0 software
      was used for statistical analysis. RESULTS: Although the mean incision size was
      significantly shorter in the MI group than in the CO group (2.8 vs. 3.5 cm), the
      mean scores from the body image questionnaire (body image score, cosmetic score,
      and self-confidence score) were similar for both groups (p > 0.05). No
      significant differences in postoperative complications were observed in these
      groups (p > 0.05). CONCLUSIONS: Studies in the literature that evaluate body
      image and cosmesis in thyroid surgery using standardized methods are scarce. In
      our department, the results of a questionnaire showed that the MI approach has no
      advantage for body image and cosmesis over the CO approach. Further prospective
      randomized studies using different tools with a larger sample size are needed to
      investigate the use of MI procedures for thyroid surgery.

PMID- 22407090
TI  - Effective mass enhancement and spin-glass behaviour in CeCu4Mn(y)Al(1-y)
      compounds.
AB  - We report on the magnetic ac/dc susceptibility and specific heat measurements for
      the CeCu(4)Mn(y)Al(1-y) series of compounds with 0 <= y <= 1. All compounds
      investigated crystallize in the hexagonal CaCu(5)-type structure with the space
      group P6/mmm. The results reveal that the frustration of the interactions
      dominates and leads to a spin-glass (SG) behaviour with a linear change of the
      freezing temperature T(f) as a function of y. The SG state has been confirmed by
      the frequency dependence of the ac magnetic susceptibility, the relaxation of the
      remanent magnetization and the split of the field-cooled-zero-field-cooled dc
      magnetic susceptibility. The electronic specific heat coefficient gamma is
      enhanced for all y and increases with the Al content. Below a threshold at y ~
      0.3, gamma is large even if determined for temperatures above T(f); moreover the
      paramagnetic Curie-Weiss temperature theta(p) changes sign to negative. These
      observations indicate the possible presence of the heavy fermion (HF) state, at
      least below y ~ 0.3, and the possible coexistence of the SG and HF states down to
      y = 0, i.e. for the CeCu(4)Al compound. A tentative magnetic phase diagram for
      CeCu(4)Mn(y)Al(1-y) has been constructed.

PMID- 22407091
TI  - Sex steroid levels temporarily increase in response to acute psychosocial stress
      in healthy men and women.
AB  - It is well known that acute psychosocial stress activates the hypothalamic
      pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). However,
      the effect of acute psychosocial stress on the hypothalamic-pituitary-gonadal
      (HPG) axis and levels of sex steroids are less known. The aim of this study was
      to investigate the effect of acute psychosocial stress on serum concentrations of
      sex steroids in healthy men and women. Twenty men and 19 women (age 30-50 years)
      underwent Trier Social Stress Test (TSST), a tool for investigating
      psychobiological stress responses in a laboratory setting. Blood samples were
      collected before, directly after the stress test, and after 30 min of recovery.
      Concentrations of androgens were measured with high specificity LC-MS/MS method;
      concentrations of cortisol, estradiol and sex hormone-binding globulin were
      determined using immunoassays. In both men and women we observed significantly
      elevated levels of testosterone, estradiol, androstenedione and sex hormone
      binding globulin along with significantly increased adrenocorticotropic hormone
      (ACTH), serum cortisol, heart rate, systolic blood pressure (SBP), and diastolic
      blood pressure (DBP) as a response to the stressor. Thus, even though the HPG
      axis and the production of sex steroids may be inhibited during prolonged periods
      of stress, the sex steroid levels may increase in the initial phase of acute
      psychosocial stress.

PMID- 22407092
TI  - [Evidence-based orthopedics in the practice].

PMID- 22407093
TI  - [Changes of patella position after closed and open wedge high tibial osteotomy:
      review of the literature].
AB  - AIM: High tibial osteotomy (HTO) is an established treatment for varus
      osteoarthritis of the knee. The correction can be achieved by lateral closed
      wedge HTO or medial open wedge HTO techniques. Both techniques can change the
      patella position which influences alignment of the patella. Patella infera may
      compromise the result of secondary total knee prosthesis. An analysis of the
      current literature was carried out focusing on changes of patella position after
      HTO. METHOD: A literature search was performed in PubMed which identified 15
      relevant publications and the Insall-Salvati-index, the Blackburne-Peel-index and
      the Caton-Deschamps-index were analyzed. RESULTS: Results after closed wedge HTO:
      the Insall-Salvati-index decreased in 7 papers, increased in 3 papers and was
      unchanged in 1 paper. The Blackburne-Peel-index increased in 5 papers and
      decreased in 2. The Caton-Deschamps-index decreased in 4 papers and increased in
      2 papers. Results after open wedge HTO: the InsalI-Salvati-index decreased in 5
      papers and increased in 2. The Blackburne-Peel-index decreased in all 7 papers
      and the Caton-Deschamps-index decreased in all 5 papers. The results of these
      studies vary significantly and there was a tendency to patella infera in both
      techniques. The Blackburne-Peel-index and the Caton-Deschamps-index may be biased
      by slope changes but the exact effect is not yet known. The Insall-Salvati-index
      seems to be independent of slope changes. The effect of different rehabilitation
      concepts on patella height is not known. CONCLUSION: The clinical relevance of
      the observed changes in patella position must be clarified by prospective studies
      with strict criteria.

PMID- 22407094
TI  - [Reduction of unstable and dislocated hips applying the Tubingen hip flexion
      splint?].
AB  - BACKGROUND: The indication for the use of the Tubingen hip flexion splint is a
      dysplastic hip without instability. According to current knowledge dysplastic
      unstable or dislocated hips should be treated with a stable retention device such
      as a modified Fettweis cast. The aim of this study was to evaluate the treatment
      effect of the Tubingen hip flexion splint when applied to dysplastic unstable
      hips (type IIc unstable according to the classification of Graf) and dislocated
      hips (types D, III and IV according to the classification of Graf) within the
      first week of life. PATIENTS AND METHODS: All newborns with an unstable hip type
      IIc or worse detected by ultrasound in the first week of life were treated with a
      Tubingen hip flexion splint. A prospective cohort trial was performed between
      November 2007 and December 2010. The initial hip type according to the ultrasound
      classification of Graf, the start and the duration of treatment with the Tubingen
      hip flexion splint as well as the rate of success were evaluated. Due to the
      small number of patients non-parametric tests were used for statistical analysis.
      RESULTS: A total of 50 dysplastic unstable or dislocated hips in 42 newborns were
      treated with the Tubingen hip flexion splint. The distribution of pathological
      hip types was 6 type IIc unstable, 33 type D, 10 type III and 1 type IV. Therapy
      was started on average on day 3.5 (range 1-8 days) of life and 49 out of 50 hips
      were successfully treated with the Tubingen hip flexion splint. Solely the type
      IV hip could not be reduced in the Tubingen hip flexion splint. Thus 98% of the
      dysplastic unstable or dislocated hips were successfully converted into type I
      hips with an alpha-angle of more than 64 degrees  in the splint. The mean time
      for achieving an alpha-angle >= 64 degrees  was 51.6 +/- 18.9 days (range 21-87
      days). No statistically significant relationship was found between the duration
      of therapy and the time when treatment was started, early or late within the
      first week of life (p = 0.152). Furthermore, no correlation was detected between
      the duration of therapy and the initial hip type determined by ultrasound (p =
      0.886). In all successfully treated cases therapy could be discontinued during
      the exponential part of Tschauner's maturation curve of hip development.
      CONCLUSION: When recognized within the first week of life dysplastic unstable
      hips (type IIc unstable according to the classification of Graf) and dislocated
      hips with a cranially dislocated cartilage roof (types D and III according to the
      classification of Graf) can be successfully treated with the Tubingen hip flexion
      splint provided that the parents show good compliance concerning the treatment
      regimen.

PMID- 22407095
TI  - [Outcome 4 years after isolated single-bundle posterior cruciate ligament
      reconstruction].
AB  - BACKGROUND: The purpose of this study was to evaluate the clinical and
      radiological results after isolated reconstruction of the posterior cruciate
      ligament (PCL) using semitendinosus (ST) and gracilis (GT) tendon grafts with the
      arthroscopic single-bundle technique. MATERIALS AND METHODS: Following PCL
      reconstruction using the single-bundle technique performed between 2002 and 2005,
      14 patients (2 women, 12 men) prospectively underwent a standardized follow-up
      examination after an average postoperative time of 4 years. All patients included
      in this study had isolated insufficiency of the PCL and symptomatic instability.
      The exclusion criteria were the presence of a complex knee joint instability and
      the implementation of additional stabilizing measures or another method of PCL
      reconstructive surgery. The mean follow-up time was 47.2 +/- 8.7 months.
      Preoperative and postoperative stress radiographs were taken using the Telos
      stress instrument in order to evaluate the posterior translation. Knee joint
      function and degree of activity were recorded using the Tegner activity score,
      the subjective IKDC score and the overall IKDC score. RESULTS: The posterior
      tibial translation of 10.1 +/- 1.7 mm had an overall average improvement to a
      postoperative value of 4.6 +/- 2.3 mm (p < 0.001). The patients showed a
      significant improvement in the Tegner activity score from an average 2.7 +/- 0.8
      points to 5.7 +/- 1.3 points (p < 0.001). Evaluation of the subjective IKDC
      showed a significant improvement from a preoperative score of 41.32 +/- 11.23
      points to a postoperative score of 65.08 +/- 13.51 points (p < 0.001). In total,
      10 patients (71.5%) exhibited a normal or nearly normal outcome. According to the
      objective IKDC score, 4 patients (28.5%) were categorized as moderate.
      CONCLUSION: The above mentioned reconstruction technique can achieve a stable
      knee function in patients with isolated PCL insufficiency. The isolated single
      bundle PCL reconstruction offers a medium-term improvement regarding the activity
      level and stability of the knee joint.

PMID- 22407096
TI  - [Recurrent hematomas of the iliopsoas muscle after total hip replacement as a
      differential diagnosis for chronic groin pain: case series report].
AB  - BACKGROUND: Chronic and atraumatic groin pain may be due to a variety of
      pathologies local to and distal from the hip joint. Aside from frequent entities,
      such as inguinal hernia, impingement of the iliopsoas muscle by the anterior rim
      of the acetabular component leading to a hematoma can be a potential cause after
      total hip replacement (THR). MATERIAL AND METHODS: This article presents three
      cases of delayed groin pain after THR received due to osteoarthrosis of the hip
      joint several years prior to the onset of symptoms. In all three cases the
      patient suffered from chronic groin pain aggravated by active flexion without
      direct trauma. After thorough clinical, laboratory and radiological (ultrasound,
      x-ray, computed tomography) examination a hematoma of the iliopsoas muscle was
      detected. Furthermore, in all three cases the acetabular component appeared to be
      slightly malpositioned. Considering the least invasive procedure all cases were
      treated with an excavation of the hematoma. After recurrence the indications for
      revision of the malpositioned acetabular component were present. RESULTS: All
      patients clearly showed a reduction of pain after operative revision. There have
      been no further hematomas and the patients could be easily and rapidly
      remobilized. CONCLUSIONS: Persistent atraumatic groin pain connected to a deficit
      in hip flexion after THR needs thorough investigation by the treating physician.
      The differential diagnosis of a delayed hematoma due to impingement of the
      iliopsoas muscle is a rare but more complex entity. After careful consideration
      of the perioperative risks an early indication for revision of a malpositioned
      acetabular component is promising.

PMID- 22407097
TI  - [Approval of a bone bank: an institution's experience].
AB  - The new tissue laws of 2007 created a completely new situation for German
      musculoskeletal tissue banks. The objective of the new regulations in the recent
      German tissue act is to improve safety by reducing the risk of transmission of
      viral and nonviral diseases. Since 2007 tissue banks have to declare their
      intention to continue providing allografts to the local authorities until August
      2011 based on the guidelines of the Federal Medical Association
      (Bundesarztekammer 2001) and according to S 144 of the Pharmaceutical Products
      Act (Arzneimittelgesetz). The Orthopedic University Clinic in Ulm applied for
      registration according to S 20 b and c of the Pharmaceutical Products Act in
      2010. After submitting all the required documents, government officials
      controlled the equipment, distribution of responsible personnel, location of
      operating theatres and the laboratory and quality assurance documentation. After
      alluding to the lack of validation for the use of a hemoculture medium for
      testing ringer lactate solutions, permission according to S 20 b and c was
      granted with the obligation to transfer all serological and microbiological
      testing of tissue donors to another laboratory with its own approval under S 20 c
      of the Pharmaceutical Products Act.

PMID- 22407099
TI  - [Rheumatic joint disease in childhood and adolescence].
AB  - Rheumatic joint disease in childhood and adolescence is relatively rare. In the
      general population, 1 child with juvenile arthritis accounts for 100 adult
      patients with rheumatoid arthritis. At disease onset 50% of affected children are
      between 2 and 6 years of age. Symptoms are often subtle and pain is usually not
      the leading symptom. Early treatment of juvenile arthritis is essential in order
      to prevent long-term sequelae in affected children. Many children are introduced
      to a pediatric rheumatologist only with considerable delay. Therapy is based on
      NSAIDs, intra-articular steroid injections, and immunosuppressive drugs. In
      severe cases patients are treated with biologics. Physical and occupational
      therapy are important supportive measures in the treatment.

PMID- 22407101
TI  - Musculoskeletal: what is different in children? Playing at school: falls into
      bleachers: left arm pain.

PMID- 22407102
TI  - Determinants of gastric CDX2 expression:  a study in Mozambique.
AB  - As CDX2 expression precedes the occurrence of gastric preneoplastic lesions in
      the intestinal differentiation pathway, study of these steps of gastric
      carcinogenesis may contribute toward understanding the early effects of gastric
      cancer determinants. Our aim was to quantify the association between Helicobacter
      pylori infection and other environmental factors and the gastric expression of
      CDX2. Dyspeptic patients undergoing an upper digestive endoscopy
      (Gastroenterology Department, Maputo Central Hospital) were consecutively invited
      to participate in this study and classified as having normal stomach/chronic
      nonatrophic gastritis (NS/CNAG), chronic atrophic gastritis (CAG), or intestinal
      metaplasia (IM). For all patients with CAG or IM and a subsample of NS/CNAG
      patients (sex-matched and age-matched, 1 : 2), H. pylori infection and CDX2 gene
      expression were assessed by histology and PCR and by immunohistochemistry,
      respectively. Age-adjusted, sex-adjusted, education-adjusted, and H. pylori
      infection-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were
      computed. CDX2 expression was observed in 56 NS/CNAG (49.1%), 39 CAG (86.7%), and
      all IM patients (n=12). It was more frequent among the H. pylori-infected
      patients (OR=2.26, 95% CI: 1.00-5.15). Infection with high-virulence strains was
      associated with CDX2 expression in patients with CAG (cagA, OR=3.20, 95% CI: 1.35
      7.52) and IM (vacA m1, OR=5.86, 95% CI: 1.08-31.62). Patients with a lower
      frequency of vegetable consumption had a higher risk of marked CDX2 expression
      (OR=3.64, 95% CI: 1.02-12.95). The virulence of the infecting strains and
      vegetable consumption were associated with CDX2 expression and may play a role in
      the progression to more advanced lesions.

PMID- 22407103
TI  - Tales of decline: reading social pathology into individual suicide in South
      India.
AB  - In the south Indian state of Kerala, the nation's so-called suicide capital,
      suicide can often appear self-evident in meaning and motivation to casual
      onlookers and experts alike. Drawing on explanatory accounts, rumors, and
      speculative tales of suicide collected between 2004 and 2007, this article
      explores the ontological power of certain deaths to assert themselves as always
      already known on the basis of perceived and reported demographic patterns of
      suicide. I demonstrate the ways suicides are commonly read, less through the
      distinct details of their individual case presentations than "up" to broader
      scales of social pathology. Shaped by the intertwined histories of public health
      intervention and state taxonomic knowledge in India, these "epidemic readings" of
      suicide enact a metonymy between individual suffering and ideas of collective
      decline that pushes the suicide case to fit-and thus to stand for-aggregate
      trends at the level of populations. Focusing on how family navigated the generic
      meanings and motivations ascribed to the deaths of their loved ones, I argue that
      the ability of kin to resist, collude with, or strategically deploy epidemic
      readings in their search for truth and closure hinged significantly on their
      classed fluency in the social, legal, and bureaucratic discourses of suicide.

PMID- 22407105
TI  - Altered expression of mitochondrial cytochrome c oxidase I and NADH dehydrogenase
      4 transcripts associated with gastric tumorigenesis and tumor dedifferentiation.
AB  - This study aimed to detect the expression of mitochondrial mRNA in normal and
      cancerous gastric tissues and discuss their association with clinicopathological
      characteristics. Semi-quantitative reverse-transcription PCR was used to analyze
      mitochondrial transcripts in 42 cases of matched cancerous and normal gastric
      tissues. Expression of these genes was then statistically analyzed to determine
      the correlation with the clinicopathological characteristics from the patients.
      Transcripts of cytochrome c oxidase I (CO I) and NADH dehydrogenase 4 (ND4) were
      highly expressed in gastric cancer tissues compared to normal gastric tissues
      (P=0.005 and P=0.001, respectively). The expression levels of CO I and ND4 were
      higher in the diffused type of gastric cancer than in the intestinal type
      (P=0.024 and P=0.0002, respectively). Elevated expression of CO I and ND4 were
      associated with gastric tumorigenesis and tumor dedifferentiation ex vivo.

PMID- 22407106
TI  - Analysis of biomarkers characteristic of porcine liver injury--from biomolecular
      logic gates to an animal model.
AB  - A biocatalytic cascade for the analysis of the simultaneous increase in the
      concentration of two biomarkers characteristic of liver injury (alanine
      transaminase, ALT, and lactate dehydrogenase, LDH) was tested on real samples
      acquired from an animal model (domestic pigs, Sus scrofa domesticus) suffering
      from traumatic liver injury. A two-step reaction biocatalyzed in the presence of
      both enzyme-biomarkers resulted in the oxidation of NADH followed by optical
      absorbance measurements. A simple qualitative, YES/NO, test allowed for
      distinction between animals with and without the presence of liver injury with
      the probability of 92%. These data represent the first demonstration of applying
      binary logic systems for the analysis of real biomedical samples.

PMID- 22407108
TI  - Conventional process for ethanol production from Indian broken rice and pearl
      millet.
AB  - A conventional process for ethanol production involving liquefaction followed by
      simultaneous saccharification and fermentation (SSF) under the yeast fermentation
      conditions, was investigated at 30 and 35% dry solid (DS) of Indian broken rice
      and pearl millet feedstocks. The study followed the typical conventional process
      currently in use by the Indian Ethanol Industry. Liquefaction was carried out
      using a thermostable alpha amylase, and whereas SSF with a glucoamylase with
      additional side activities of pullulanase and protease under the yeast
      fermentation conditions. To measure the enzyme efficacy in the liquefaction
      process, fermentable sugar and liquefact solubility (brix) were monitored at the
      end of the liquefaction process. The liquefact was subjected to SSF with yeast.
      Addition of an acid fungal protease at a concentration of 0.1 kg per metric ton
      of grain during SSF was observed to accelerate yeast growth and ultimately,
      ethanol yield with both feedstocks. With both concentrations of feedstocks, the
      fermentation efficiency and ethanol recovery were determined. This study assesses
      the potential of these enzymes for ethanol production with higher dry solid
      concentration (>=30% w/w DS) of both these feedstocks in the conventional process
      to achieve higher plant throughput without compromising fermentation efficiency
      and ethanol recovery.

PMID- 22407109
TI  - Diagnosing personality disorders.

PMID- 22407107
TI  - Role of monocarboxylate transporters in human cancers: state of the art.
AB  - Monocarboxylate transporters (MCTs) belong to the SLC16 gene family, presently
      composed by 14 members. MCT1-MCT4 are proton symporters, which mediate the
      transmembrane transport of pyruvate, lactate and ketone bodies. The role of MCTs
      in cell homeostasis has been characterized in detail in normal tissues, however,
      their role in cancer is still far from understood. Most solid tumors are known to
      rely on glycolysis for energy production and this activity leads to production of
      important amounts of lactate, which are exported into the extracellular milieu,
      contributing to the acidic microenvironment. In this context, MCTs will play a
      dual role in the maintenance of the hyper-glycolytic acid-resistant phenotype of
      cancer, allowing the maintenance of the high glycolytic rates by performing
      lactate efflux, and pH regulation by the co-transport of protons. Thus, they
      constitute attractive targets for cancer therapy, which have been little
      explored. Here we review the literature on the role of MCTs in solid tumors in
      different locations, such as colon, central nervous system, breast, lung,
      gynecologic tract, prostate, stomach, however, there are many conflicting results
      and in most cases there are no functional studies showing the dependence of the
      tumors on MCT expression and activity. Additional studies on MCT expression in
      other tumor types, confirmation of the results already published as well as
      additional functional studies are needed to deeply understand the role of MCTs in
      cancer maintenance and aggressiveness.

PMID- 22407110
TI  - How good are observational studies in assessing psychiatric treatment outcomes?

PMID- 22407111
TI  - Are adults just big children?

PMID- 22407112
TI  - Silent cerebrovascular events and Alzheimer's disease: an overlooked opportunity
      for prevention?

PMID- 22407113
TI  - Images in psychiatry. Zoroastrian priests: ancient Persian psychiatrists.

PMID- 22407115
TI  - Five new schizophrenia loci may converge on the same cellular mechanism: the AKT
      pathway.

PMID- 22407114
TI  - The effect of gastric bypass on the pharmacokinetics of serotonin reuptake
      inhibitors.
AB  - OBJECTIVE: Morbidly obese patients frequently present with mood and anxiety
      disorders, which are often treated with serotonin reuptake inhibitors (SRIs).
      Having observed that patients treated with SRIs frequently relapse after Roux-en
      Y gastric bypass surgery, the authors sought to assess whether SRI
      bioavailability is reduced postoperatively. METHOD: Twelve gastric bypass
      candidates treated with an SRI for primary mood or anxiety disorders were studied
      prospectively. Timed blood samples for SRI plasma levels were drawn for
      pharmacokinetic studies before surgery and 1, 6, and 12 months afterward. Maximum
      concentration, time to maximum concentration, and area under the
      concentration/time curve (AUC) were determined. RESULTS: In eight of the 12
      patients, AUC values 1 month after surgery dropped to an average of 54% (SD=18)
      of preoperative levels (range=36%-80%); in six of these patients, AUC values
      returned to baseline levels (or greater) by 6 months. Four patients had an
      exacerbation of depressive symptoms, which resolved by 12 months in three of
      them. Three of the four patients had a reduced AUC level at 1 month and either
      gained weight or failed to lose weight between 6 and 12 months. Normalization of
      the AUC was associated with improvement in symptom scores. CONCLUSIONS: Patients
      taking SRIs in this study were at risk for reduced drug bioavailability 1 month
      after Roux-en-Y gastric bypass. The authors recommend close psychiatric
      monitoring after surgery.

PMID- 22407122
TI  - Psychiatric violence risk assessment.

PMID- 22407124
TI  - Maternal request: a reason for rising rates of cesarean section?
AB  - OBJECTIVE: The rising rate of cesarean sections (CS), especially those on
      maternal request, is an important obstetric care issue. The aim of this two-point
      cross-sectional study was to evaluate the prevalence of CS and their indications.
      METHODS: We performed a retrospective chart review of the indications of all CS
      performed at a tertiary care clinic in Switzerland in 2002 and 2008. Chi-square,
      Student's t and Mann-Whitney U tests were performed to identify significant
      differences. RESULTS: The number of CS rose from 23.3% (371 out of 1,594 total
      life births) in 2002 to 27.5% (513 out of 1,866) in 2008 (p = 0.005). Of all
      deliveries, the rate of CS on maternal request and, among these, especially those
      requested after previous CS, increased significantly (2.1 vs. 5.1% and 0.3 vs.
      1.2%, respectively). The number of CS due to previous traumatic birth experience
      nearly doubled (0.7 vs. 1.2%, not significant). Maternal and fetal complications
      were rare but not negligible in the subset of low-risk patients requesting CS.
      CONCLUSIONS: The study demonstrated a significant increase in CS on maternal
      request, especially in case of previous CS. The findings of this study support
      the need for specific counseling strategies for women requesting delivery by CS.

PMID- 22407126
TI  - Solid-phase-assisted synthesis of targeting peptide-PEG-oligo(ethane amino)amides
      for receptor-mediated gene delivery.
AB  - In the forthcoming era of cancer gene therapy, efforts will be devoted to the
      development of new efficient and non-toxic gene delivery vectors. In this regard,
      the use of Fmoc/Boc-protected oligo(ethane amino)acids as building blocks for
      solid-phase-supported assembly represents a novel promising approach towards
      fully controlled syntheses of effective gene vectors. Here we report on the
      synthesis of defined polymers containing the following: (i) a plasmid DNA (pDNA)
      binding domain of eight succinoyl-tetraethylenpentamine (Stp) units and two
      terminal cysteine residues; (ii) a central polyethylene glycol (PEG) chain (with
      twenty-four oxyethylene units) for shielding; and (iii) specific peptides for
      targeting towards cancer cells. Peptides B6 and c(RGDfK), which bind transferrin
      receptor and alpha(v)beta(3) integrin, respectively, were chosen because of the
      high expression of these receptors in many tumoral cells. This study shows the
      feasibility of designing these kinds of fully controlled vectors and their
      success for targeted pDNA-based gene transfer.

PMID- 22407127
TI  - Prognostic value of volumetric parameters measured by F-18 FDG PET/CT in
      surgically resected non-small-cell lung cancer.
AB  - OBJECTIVES: The aim of this study was to evaluate the usefulness of the tumor
      burden as characterized by the metabolic tumor volume (MTV) and total lesion
      glycolysis (TLG) measured by F-18 fluoro-2-deoxyglucose (F-18 FDG) PET-computed
      tomography (CT) in predicting recurrence-free survival (RFS) and overall survival
      (OS) in surgically resected non-small-cell lung cancer (NSCLC) patients. METHODS:
      We retrospectively reviewed 91 patients with pathologically documented stages I
      IIIA NSCLC. MTV and TLG were obtained according to various thresholds of the
      standard uptake value (SUV) of primary tumor using preoperative F-18 FDG PET-CT.
      We used comparison receiver-operating characteristic curve analysis to test the
      statistical significance of the differences among the multiple volumetric
      parameters calculated by various SUV cutoff values. RFS and OS were evaluated
      with the Kaplan-Meier method and Cox regression analysis. RESULTS: On comparison
      receiver-operating characteristic curve analysis, no significant difference was
      found among the volumetric parameters calculated using various thresholds of SUV.
      Regardless of the thresholds, patients with smaller MTV and lower TLG showed
      longer RFS and OS. MTV and TLG measured by F-18 FDG PET-CT were found to have
      better predictive performance than SUVmax for recurrence and death. According to
      multivariate analyses, MTV2.5 was revealed as a significant prognostic factor for
      RFS. Tumor size over 3 cm was selected as a significant prognostic indicator of
      OS. CONCLUSION: Volume-based parameters of F-18 FDG PET-CT may have a role in
      providing prognostic information in NSCLC patients who have received surgical
      treatment.

PMID- 22407128
TI  - Drug eruption due to sodium picosulfate.

PMID- 22407129
TI  - Human and mouse ZFY genes produce a conserved testis-specific transcript encoding
      a zinc finger protein with a short acidic domain and modified transactivation
      potential.
AB  - Mammalian ZFY genes are located on the Y chromosome, and code putative
      transcription factors with 12-13 zinc fingers preceded by a large acidic
      (activating) domain. In mice, there are two genes, Zfy1 and Zfy2, which are
      expressed mainly in the testis. Their transcription increases in germ cells as
      they enter meiosis, both are silenced by meiotic sex chromosome inactivation
      (MSCI) during pachytene, and Zfy2 is strongly reactivated later in spermatids.
      Recently, we have shown that mouse Zfy2, but not Zfy1, is involved in triggering
      the apoptotic elimination of specific types of sex chromosomally aberrant
      spermatocytes. In humans, there is a single widely transcribed ZFY gene, and
      there is no evidence for a specific role in the testis. Here, we characterize ZFY
      transcription during spermatogenesis in mice and humans. In mice, we define a
      variety of Zfy transcripts, among which is a Zfy2 transcript that predominates in
      spermatids, and a Zfy1 transcript, lacking an exon encoding approximately half of
      the acidic domain, which predominates prior to MSCI. In humans, we have
      identified a major testis-specific ZFY transcript that encodes a protein with the
      same short acidic domain. This represents the first evidence that ZFY has a
      conserved function during human spermatogenesis. We further show that, in
      contrast to the full acidic domain, the short domain does not activate
      transcription in yeast, and we hypothesize that this explains the functional
      difference observed between Zfy1 and Zfy2 during mouse meiosis.

PMID- 22407131
TI  - Open-loop band excitation Kelvin probe force microscopy.
AB  - A multidimensional scanning probe microscopy approach for quantitative, cross
      talk free mapping of surface electrostatic properties is demonstrated. Open-loop
      band excitation Kelvin probe force microscopy (OL BE KPFM) probes the full
      response-frequency-potential surface at each pixel at standard imaging rates. The
      subsequent analysis reconstructs work function, tip-surface capacitance gradient
      and resonant frequency maps, obviating feedback-related artifacts. OL BE KPFM
      imaging is demonstrated for several materials systems with topographic, potential
      and combined contrast. This approach combines the features of both frequency and
      amplitude KPFM and allows complete decoupling of topographic and voltage
      contributions to the KPFM signal.

PMID- 22407130
TI  - Identification of CSK as a systemic sclerosis genetic risk factor through Genome
      Wide Association Study follow-up.
AB  - Systemic sclerosis (SSc) is complex autoimmune disease affecting the connective
      tissue; influenced by genetic and environmental components. Recently, we
      performed the first successful genome-wide association study (GWAS) of SSc. Here,
      we perform a large replication study to better dissect the genetic component of
      SSc. We selected 768 polymorphisms from the previous GWAS and genotyped them in
      seven replication cohorts from Europe. Overall significance was calculated for
      replicated significant SNPs by meta-analysis of the replication cohorts and
      replication-GWAS cohorts (3237 cases and 6097 controls). Six SNPs in regions not
      previously associated with SSc were selected for validation in another five
      independent cohorts, up to a total of 5270 SSc patients and 8326 controls. We
      found evidence for replication and overall genome-wide significance for one novel
      SSc genetic risk locus: CSK [P-value = 5.04 * 10(-12), odds ratio (OR) = 1.20].
      Additionally, we found suggestive association in the loci PSD3 (P-value = 3.18 *
      10(-7), OR = 1.36) and NFKB1 (P-value = 1.03 * 10(-6), OR = 1.14). Additionally,
      we strengthened the evidence for previously confirmed associations. This study
      significantly increases the number of known putative genetic risk factors for
      SSc, including the genes CSK, PSD3 and NFKB1, and further confirms six previously
      described ones.

PMID- 22407132
TI  - Susceptibility to weight gain. Eating behaviour traits and physical activity as
      predictors of weight gain during the first year of university.
AB  - The transition to University has been identified as a possible period for weight
      gain but few studies have addressed the extent of this experience in UK
      Universities. The present study was conducted in four Universities in England and
      Scotland to directly measure changes in body weight, waist circumference and body
      composition in students during their first year. Two hundred and fifty first-year
      students completed psychometric eating behaviour questionnaires and a validated
      physical activity survey before attending one of the laboratories for
      standardised assessments of height, body weight, waist circumference and body
      composition at 0, 3, and 12-months. Significant but small and transitory
      increases in all weight outcomes (e.g. body weight=0.83+/-2.1 kg) were observed
      except for fat-free mass. Weight-related measures at baseline predicted changes
      in weight over 12-months but not 3-months. Disinhibition, power of food and binge
      eating were associated with change in fat mass while physical activity, cognitive
      restraint and sensitivity to reward were associated with change in fat-free mass.
      Weight gain occurs in the first year of University in the UK, but appears to be
      small and transitory. Changes in fat mass were related to opportunistic eating
      and the tendency to overconsume, while change in fat-free mass related to
      physical activity and low dietary restraint in conjunction with drive to
      experience reward. Psychological markers underlying changes in body composition
      can inform strategies to promote self-regulation in young adults during a
      critical life period for weight gain.

PMID- 22407133
TI  - Changing micronutrient intake through (voluntary) behaviour change. The case of
      folate.
AB  - The objective of this study was to relate behaviour change mechanisms to
      nutritionally relevant behaviour and demonstrate how the different mechanisms can
      affect attempts to change these behaviours. Folate was used as an example to
      illuminate the possibilities and challenges in inducing behaviour change. The
      behaviours affecting folate intake were recognised and categorised. Behaviour
      change mechanisms from "rational model of man", behavioural economics, health
      psychology and social psychology were identified and aligned against folate
      related behaviours. The folate example demonstrated the complexity of mechanisms
      influencing possible behavioural changes, even though this only targets the
      intake of a single micronutrient. When considering possible options to promote
      folate intake, the feasibility of producing the desired outcome should be related
      to the mechanisms of required changes in behaviour and the possible alternatives
      that require no or only minor changes in behaviour. Dissecting the theories
      provides new approaches to food-related behaviour that will aid the development
      of batteries of policy options when targeting nutritional problems.

PMID- 22407134
TI  - Non-food odorants reduce chocolate cravings.
AB  - The present study compared the relative effectiveness of simple, commercially
      available food and non-food olfactory tasks on chocolate craving reduction.
      Chocolate cravings were induced by a series of coloured photographs and 67
      undergraduate women were asked to smell one of three odours (green apple,
      jasmine, or water). The non-food odorant (jasmine) significantly reduced
      chocolate cravings relative to both the food and control odorants. Thus simple
      non-food odorants offer potential scope as a technique for curbing unwanted food
      cravings.

PMID- 22407135
TI  - More than just a pretty face. The relationship between infant's temperament, food
      acceptance, and mothers' perceptions of their enjoyment of food.
AB  - The goal of the present study was to determine whether mothers' assessment of
      their infants' temperament is associated with objective measures of the infant's
      acceptance patterns and their judgments of the infants' liking of a green
      vegetable. To this end, infants (N=92) were video-recorded as their mothers fed
      them green beans. From these videos, we determined the frequency of facial
      distaste expressions made during the first 2 min of the feeding. Other measures
      included intake, maternal ratings of infants' enjoyment of this vegetable, and
      temperament. Infants who scored high on the approach dimension of the temperament
      questionnaire were less likely to express facial expressions of distaste,
      consumed more food, and were perceived by their mothers as enjoying the food
      more. Mediation analyses revealed that ratings of enjoyment were not directly
      related to the child's approach temperament, but rather the relationship between
      mothers' ratings and temperament was mediated by the amount of time infants spent
      eating the vegetable. Regression analyses suggested that in addition to the
      length of time children ate, mothers' ratings of their infants' enjoyment was
      predicted by the number of squints that the infant expressed during the meal.
      These findings suggest that although certain aspects of children's temperament
      are related to their food acceptance, mothers attend to facial expressions and
      time spent eating independently of these temperamental characteristics when
      judging their infant's enjoyment of a food. Understanding how mothers use this
      information to decide which foods to feed their infants is an important area for
      future research.

PMID- 22407136
TI  - Poultry and livestock exposure and cancer risk among farmers in the agricultural
      health study.
AB  - PURPOSE: The purpose of this study is to evaluate cancer risk associated with
      raising animals as commodities, which is associated with a variety of exposures,
      such as infectious agents and endotoxins. METHODS: Information was available for
      49,884 male farmers in the Agricultural Health Study, who reported livestock and
      poultry production at enrollment (1993-1997). Cancer incidence data were obtained
      through annual linkage to state registries. Using Poisson regression analyses, we
      evaluated whether the number and type of animals raised on the farm impacted
      cancer risk. RESULTS: Overall, 31,848 (63.8%) male farmers reported raising any
      animals. Lung cancer risk decreased with increasing number of livestock on the
      farm (p trend = 0.04) and with raising poultry (Relative Risk (RR) = 0.6; 95%
      confidence interval (CI): 0.4-0.97). Raising poultry was associated with an
      increased risk of colon cancer (RR = 1.4; 95% CI: 0.99-2.0) with further
      increased with larger flocks (p trend = 0.02). Risk of non-Hodgkin lymphoma was
      also elevated in those who raised poultry (RR = 1.6; 95% CI: 1.0-2.4), but there
      was no evidence of increased risk with larger flocks (p trend = 0.5). Raising
      sheep was associated with a significantly increased risk of multiple myeloma (RR
      = 4.9; 95% CI: 2.4-12.0). Performing veterinary services increased the risk of
      Hodgkin lymphoma (RR = 12.2; 95% CI: 1.6-96.3). CONCLUSIONS: We observed an
      inverse association between raising poultry and livestock and lung cancer risk
      and some evidence of increased risk of specific lymphohematopoietic malignancies
      with specific types of animals and performing veterinary services. Further
      research into associations between raising animals and cancer risk should focus
      on identification of etiologic agents.

PMID- 22407137
TI  - Caffeinated beverage and soda consumption and time to pregnancy.
AB  - BACKGROUND: Many epidemiologic studies have evaluated the association between
      caffeine and fertility, with inconsistent results. Some studies suggest that
      various caffeine-containing beverages may affect fertility differently. METHODS:
      We evaluated the relation of caffeine, coffee, tea, and sodas with time to
      pregnancy in a prospective cohort study of 3628 women planning a pregnancy, in
      Denmark (2007-2010). Women reported beverage intake at baseline and every 8 weeks
      during follow-up until they became pregnant or for up to 12 cycles. We used
      discrete-time Cox proportional hazards regression to estimate fecundability
      ratios (FRs) and 95% confidence intervals (CIs), controlling for potential
      confounders. RESULTS: There was little relation between fecundability and
      caffeine intake of 300+ mg/day compared with < 100 mg/day (FR = 1.04 [95% CI =
      0.90-1.21]) or coffee intake of 3+ servings/day compared with none (1.05 [0.85
      1.33]). Soda consumption was associated with reduced fecundability: for all types
      of sodas combined, the adjusted FRs were 0.89 (0.80-0.98), 0.85 (0.71-1.02), 0.84
      (0.57-1.25), and 0.48 (0.21-1.13) for < 1, 1, 2, and 3+ servings per day,
      respectively, compared with none. Tea drinking was associated with a slight
      increase in fecundability, with FR = 1.27 (0.98-1.64) for 2+ servings/day versus
      none. CONCLUSION: In this prospective study of time to pregnancy, the association
      between caffeine intake and fertility differed by beverage type. Although we
      controlled for many confounders, our findings of reduced fecundability among soda
      drinkers and increased fecundability among tea drinkers could have resulted from
      confounding by unmeasured lifestyle characteristics.

PMID- 22407138
TI  - Ambient particulate matter and lung function growth in Chinese children.
AB  - BACKGROUND: Exposure to particulate matter (PM) has been associated with deficits
      in lung function growth among children in Western countries. However, few studies
      have explored this association in developing countries, where PM levels are often
      substantially higher. METHODS: Children (n = 3273) 6-12 years of age were
      recruited from 8 schools in 4 Chinese cities. The lung function parameters of
      forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were
      measured using computerized spirometers twice a year for up to 3 years (1993
      1996). Dichotomous samplers placed in each schoolyard were used to measure PM2.5
      and PM10 (PM with diameter <= 2.5 MUm and <= 10 MUm, respectively). Multivariable
      generalized estimating equations were used to examine the association between the
      quarterly average PM levels and lung function growth during the period of follow
      up. RESULTS: Annual average PM2.5 and PM10 levels in the 4 cities ranged from 57
      to 158 MUg/m and 95 to 268 MUg/m, respectively. In multivariable models, an
      increase of 10 MUg/m of PM2.5 was associated with decreases of 2.7 mL FEV1 (95%
      confidence interval = -3.5 to -2.0), 3.5 mL FVC (-4.3 to -2.7), 1.4 mL/year FEV1
      growth (-1.8 to -0.9), and 1.5 mL/year FVC growth (-2.0 to -1.0). Similar results
      were seen with PM10 exposure. CONCLUSIONS: Exposure to ambient particulate matter
      was associated with decreased growth in lung function among Chinese children.

PMID- 22407139
TI  - Addressing the identification problem in age-period-cohort analysis: a tutorial
      on the use of partial least squares and principal components analysis.
AB  - In the analysis of trends in health outcomes, an ongoing issue is how to separate
      and estimate the effects of age, period, and cohort. As these 3 variables are
      perfectly collinear by definition, regression coefficients in a general linear
      model are not unique. In this tutorial, we review why identification is a
      problem, and how this problem may be tackled using partial least squares and
      principal components regression analyses. Both methods produce regression
      coefficients that fulfill the same collinearity constraint as the variables age,
      period, and cohort. We show that, because the constraint imposed by partial least
      squares and principal components regression is inherent in the mathematical
      relation among the 3 variables, this leads to more interpretable results. We use
      one dataset from a Taiwanese health-screening program to illustrate how to use
      partial least squares regression to analyze the trends in body heights with 3
      continuous variables for age, period, and cohort. We then use another dataset of
      hepatocellular carcinoma mortality rates for Taiwanese men to illustrate how to
      use partial least squares regression to analyze tables with aggregated data. We
      use the second dataset to show the relation between the intrinsic estimator, a
      recently proposed method for the age-period-cohort analysis, and partial least
      squares regression. We also show that the inclusion of all indicator variables
      provides a more consistent approach. R code for our analyses is provided in the
      eAppendix.

PMID- 22407140
TI  - Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative
      marker for representative tissue samples in stereotactic brain tumor biopsies.
AB  - Stereotactic biopsies represent a routine neurosurgical procedure for the
      diagnosis of intracranial lymphomas and selected diffusely infiltrating gliomas.
      Acquisition of tissue samples that do not allow correct tumor typing and grading
      is, however, not uncommon. Five-aminolevulinic acid (5-ALA) has been shown to
      accumulate in malignant tumor tissue. The aim of this study was to prospectively
      investigate the clinical usability of 5-ALA for intraoperative detection of
      representative tissue in stereotactic tumor biopsies. Fifty consecutive patients
      underwent frameless stereotactic biopsy for a suspected brain tumor. 5-ALA was
      administered 4 h before anesthesia. Serial biopsy samples were obtained and
      intraoperatively checked for 5-ALA fluorescence (strong, vague, or none) using a
      modified neurosurgical microscope. All samples were examined for the presence of
      representative tumor tissue according to neuroimaging (MRI, positron emission
      tomography, and/or chemical shift imaging) and histopathological parameters.
      Visible 5-ALA fluorescence was observed in 43/50 patients (strong in 39 and vague
      fluorescence in four cases). At biopsy target, 52/53 samples of glioblastomas,
      9/10 samples of gliomas grade III, and 14/16 samples of lymphomas revealed strong
      5-ALA fluorescence. Samples with strong 5-ALA fluorescence were only observed at,
      but not outside the biopsy target. All tissue samples with strong 5-ALA
      fluorescence were representative according to our neuroimaging and
      histopathological criteria (positive predictive value of 100%). Our data indicate
      that strong 5-ALA fluorescence is a reliable and immediately available
      intraoperative marker of representative tumor tissue of malignant gliomas and
      intracranial lymphomas in stereotactic biopsies. Thereby, the application of 5
      ALA in stereotactic brain tumor biopsies may in future reduce costs for operating
      room and neuropathology and may decrease procedure-related morbidity.

PMID- 22407141
TI  - Clinical review: Spinal imaging for the adult obtunded blunt trauma patient:
      update from 2004.
AB  - PURPOSE: Controversy exists over how to 'clear' (we mean enable the clinician to
      safely remove spinal precautions based on imaging and/or clinical examination)
      the spine of significant unstable injury among clinically unevaluable obtunded
      blunt trauma patients (OBTPs). This review provides a clinically relevant update
      of the available evidence since our last review and practice recommendations in
      2004. METHODS: Medline, Embase. Google Scholar, BestBETs, the trip database, BMJ
      clinical evidence and the Cochrane library were searched. Bibliographies of
      relevant studies were reviewed. RESULTS: Plain radiography has low sensitivity
      for detecting unstable spinal injuries in OBTPs whereas multidetector-row
      computerised tomography (MDCT) approaches 100%. Magnetic resonance imaging (MRI)
      is inferior to MDCT for detecting bony injury but superior for detecting soft
      tissue injury with a sensitivity approaching 100%, although 40% of such injuries
      may be stable and 'false positive'. For studies comparing MDCT with MRI for
      OBTPs; MRI following 'normal' CT may detect up to 7.5% missed injuries with an
      operative fixation in 0.29% and prolonged collar application in 4.3%. Increasing
      data is available on the complications associated with prolonged spinal
      immobilisation among a population where a minority have an actual injury.
      CONCLUSIONS: Given the variability of screening performance it remains acceptable
      for clinicians to clear the spine of OBTPs using MDCT alone or MDCT followed by
      MRI, with implications to either approach. Ongoing research is needed and
      suggestions are made regarding this. It is essential clinicians and institutions
      audit their data to determine their likely screening performances in practice.

PMID- 22407142
TI  - Detecting pediatric delirium: development of a rapid observational assessment
      tool.
AB  - OBJECTIVE: Development of a novel screening tool for the detection of delirium in
      pediatric intensive care unit (PICU) patients of all ages by comparison with
      psychiatric assessment based on the reference standard Diagnostic and Statistical
      Manual of Mental Disorders (DSM-IV) criteria. METHODS: This was a prospective
      blinded pilot study investigating the feasibility of the Cornell Assessment of
      Pediatric Delirium (CAP-D) performed in a PICU at a university hospital. Fifty
      patients, ages 3 months to 21 years, admitted to the PICU over a 6-week period
      were included. No interventions were performed. RESULTS: After informed consent
      was obtained, two study teams independently assessed for delirium by completing
      the CAP-D and by conducting psychiatric evaluation based on the DSM-IV criteria.
      Concordance between the CAP-D and DSM-IV criteria was excellent, at 97%.
      Prevalence of delirium in this sample was 29%. CONCLUSION: The CAP-D may be a
      valid screen for identification of delirium in PICU patients of all ages. Further
      studies are required to explore its validity, inter-rater reliability, and
      feasibility of use as a nursing screen.

PMID- 22407143
TI  - Retraction of "Concomitant measurement of copeptin and high-sensitivity troponin
      for fast and reliable rule out of acute myocardial infarction".

PMID- 22407145
TI  - The role of surrogate markers in the management of men with metastatic castration
      resistant prostate cancer.
AB  - Over the past year, the treatment of metastatic castration-resistant prostate
      cancer (mCRPC) was dramatically altered with the introduction of several novel
      agents. One of these agents, the cancer immunotherapy sipuleucel-T, represents a
      major change in the treatment paradigm for patients with mCRPC. While
      immunotherapies such as sipuleucel-T are associated with a significant
      improvement in overall survival, many questions remain regarding their use.
      Specifically, there are questions as to which endpoints should be used to measure
      benefit with immunotherapy. Clinical trials of sipuleucel-T demonstrated that the
      traditional endpoints normally used in mCRPC trials, such as progression-free
      survival, are not good measures of response with immunotherapy. However,
      measurement of overall survival is difficult in the clinical trial setting. There
      is now a major interest in the identification of surrogate biomarkers of survival
      that could allow the benefit of novel agents to be more precisely determined.
      Many potential biomarkers have been identified, often from studies showing their
      prognostic potential. In this roundtable, experts discuss the role of biomarkers
      in measuring response to immunotherapy for men with mCRPC.

PMID- 22407146
TI  - Of mugs, meals and more: the intricate relations between physicians and the
      medical industry.
AB  - Empirical research has proven the influence exerted by the medical industry on
      physicians' decision-making. Physicians are the gatekeepers who determine how
      money is spent within the healthcare system. Hence, they are the target group of
      powerful lobbies in the field, i.e. the manufacturers of medical devices and the
      pharmaceutical industry. As clinical research lies in the hands of physicians,
      they play an exclusive and central role in launching new medical products. There
      are many ethical problems involved here: physicians may develop a mindset of
      entitlement; biased decisions may put patients at risk; academic interests and
      research activities will no longer be free if they are influenced considerably by
      financial incentives; fair resource allocation may be restricted. An aspect that
      has been neglected so far is the administrators' involvement as they not rarely
      expect physicians to acquire external financial resources from industry as
      benefits often lie with the institutions. To "protect" physicians from undue sway
      may be in the best interest of patients in order to guarantee a fair allocation
      of resources and to prevent the application of technologies (and medications)
      that would not have been used according to current standards of care. The latter
      may and obviously does put patients at risk. On the other hand, medico-industrial
      relations are of great importance. A considerable part of medical progress is
      driven by private industry. Yet, any co-operation between those who care for
      patients and industry ultimately has to serve the patient. Hence, strong policies
      to guide conduct are sorely needed. The following points are held to be pivotal
      in order to secure ethical conduct: (1) professional codes of ethics; (2) a
      stronger academic attitude amongst medical staff, (3) rules of transparency for
      medico-industrial relations including online disclosure and limiting scale of
      payments, (4) establishing rules (and laws) that ban unethical conduct and
      mandate vigorous surveillance of adherence to guidelines.

PMID- 22407148
TI  - A unique MUC1-2-VNTR DNA vaccine suppresses tumor growth and prolongs survival in
      a murine multiple myeloma model.
AB  - Multiple myeloma (MM) is a clonal B-cell malignancy charactered by the aberrant
      proliferation of malignant plasma cells in the bone marrow. MM is still an
      incurable malignancy. In this regard, novel treatments are urgently required.
      MUC1 (mucin 1), a type I transmembrane protein, is overexpressed and aberrantly
      glycosylated in many carcinomas particularly in MM resulting in an antigenically
      distinct molecule and may be a potential target for specific immunotherapy. In
      this study, we first designed a unique DNA vaccine, termed MUC1-2-VNTR (various
      number tandem repeats) to investigate whether the vaccine could specifically
      suppress tumor growth in a murine multiple myloma model. Our results showed that
      the constructed DNA vaccine pcDNA3.1-VNTR elicited both humoral and cellular
      tumor-specific immune responses in the MM mouse model leading to delay in tumor
      growth and prolonged survival of the mice. Consequently, our study indicates that
      this DNA vaccine shows promise to be used as a novel strategy for the treatment
      of MM.

PMID- 22407150
TI  - Glucocorticoid sensitivity and proinflammatory cytokines pattern in pemphigus.
AB  - Glucocorticoids (GC) represent the main treatment for pemphigus; however, some
      patients show GC resistance. GC sensitivity was evaluated in 19 pemphigus
      patients and 41 controls by the number of binding sites [B(max) (fmol/mg
      protein)] and the affinity of GC receptor [Kd (nM)] to dexamethasone (DEX) as
      well as by the pattern of cytokine by DEX-mediated inhibition of concanavalin-A
      (Con-A)-stimulated PBMC proliferation. The Kd (15.7 +/- 2.8 vs.8.1 +/- 1.3) and
      Bmax (6.5 +/- 0.9 vs. 3.9 +/- 0.3) were higher in pemphigus than controls (p =
      0.002). Considering the values above the 95th percentile of normal group as a cut
      off (K(d) > 24.9 nM and B(max) > 8.1 fmol/mg protein), elevated K(d) and B(max)
      were observed in 9.8% and 2.4% of controls and 15.8% and 36.8% of patients (p =
      0.02). PBMC proliferation was stimulated by Con-A and inhibited by DEX (p <
      0.001) in both pemphigus and control groups. IL-6 and TNFalpha (pg/mL) basal
      production were higher in patients than controls. There was an increment of these
      cytokines after Con-A stimulation, and they were inhibited by DEX (p = 0.002) in
      controls and remained elevated in pemphigus (p < 0.02). Patients and controls
      showed no difference in basal and stimulated production of IL-8 and IL-10. There
      is an alteration on GC sensitivity in pemphigus patients and a higher production
      of proinflammatory cytokines. Therefore, in pemphigus patients, proinflammatory
      cytokines might be involved in the mechanism of GC resistance and/or in its
      maintenance.

PMID- 22407151
TI  - Robotically assisted laparoscopy for paraaortic lymphadenectomy: technical
      description and results of an initial experience.
AB  - OBJECTIVE: The objective of this study is to demonstrate the feasibility of
      robotically assisted laparoscopy paraaortic lymphadenectomy (PAL), isolated or
      combined with another procedure using different surgical approaches. METHODS:
      From February 2007 to December 2010, 53 patients underwent paraaortic
      lymphadenectomy up to the left renal vein. We used three different approaches
      with three different positions for the robot in relation to the surgical
      procedure (isolated transperitoneal PAL, isolated extraperitoneal PAL, or
      transperitoneal PAL combined with another procedure). Thirty-nine patients
      underwent isolated lomboaortic lymphadenectomy and 14 a combined procedure.
      Information concerning installation time, operative time, peri- and postoperative
      complications, blood loss, lymph node count, and conversion rate was recorded.
      RESULTS: For the whole population, mean installation time was 33 +/- 18 min, mean
      operative time was 197 +/- 81 min, and mean hospital stay was 3.9 +/- 2.8 days.
      We observed 15.1% lymph node involvement at definitive pathology. Between
      isolated trans- and extraperitoneal PAL, only body mass index (BMI, 27.4 versus
      22 kg/m(2)) was significantly different. No difference was observed concerning
      mean number of lymph nodes or hospital stay. We observed statistical difference
      between combined and isolated PAL concerning mean operative time (256 versus 160
      min), mean number of lymph nodes (7.8 versus 14.6), and hospital stay (5.9 versus
      2.9 days). CONCLUSIONS: Although laparoscopic robotic-assisted PAL is a safe and
      feasible procedure, lymph node staging seems to be better if the procedure is
      isolated. In case of combined procedures, the surgical approach should be
      modified regarding patient BMI and the associated procedure, to increase lymph
      node count.

PMID- 22407152
TI  - Surgical management of acute cholecystitis: results of a 2-year prospective
      multicenter survey in Belgium.
AB  - BACKGROUND: Laparoscopic cholecystectomy is considered nowadays as the standard
      management of acute cholecystitis (AC). However, results from multicentric
      studies in the general surgical community are still lacking. METHODS: A
      prospective multicenter survey of surgical management of AC patients was
      conducted over a 2-year period in Belgium. Operative features and patients'
      clinical outcome were recorded. The impact of independent predictive factors on
      the choice of surgical approach, the risk of conversion, and the occurrence of
      postoperative complications was studied by multivariate logistic regression
      analysis. RESULTS: Fifty-three surgeons consecutively and anonymously included
      1,089 patients in this prospective study. A primary open approach was chosen in
      74 patients (6.8%), whereas a laparoscopic approach was the first option in 1,015
      patients (93.2%). Independent predictive factors for a primary open approach were
      previous history of upper abdominal surgery [odds ratio (OR) 4.13, p < 0.001],
      patient age greater than 70 years (OR 2.41, p < 0.05), surgeon with more than 10
      years' experience (OR 2.08, p = 0.005), and gangrenous cholecystitis (OR 1.71, p
      < 0.05). In the laparoscopy group, 116 patients (11.4%) required conversion to
      laparotomy. Overall, 38 patients (3.5%) presented biliary complications and 49
      had other local complications (4.5%). Incidence of bile duct injury was 1.2% in
      the whole series, 2.7% in the open group, and 1.1% in the laparoscopy group.
      Sixty patients had general complications (5.5%). The overall mortality rate was
      0.8%. All patients who died were in poor general condition [American Society of
      Anesthesiologists (ASA) III or IV]. CONCLUSIONS: Although laparoscopic
      cholecystectomy is currently considered as the standard treatment for acute
      cholecystitis, an open approach is still a valid option in more advanced disease.
      However, overall mortality and incidence of bile duct injury remain high.

PMID- 22407153
TI  - Combined transurethral approach with Versapoint((r)) and laparoscopic treatment
      in the management of bladder endometriosis: technique and 12 months follow-up.
AB  - BACKGROUND: When endometriosis infiltrates more than 5 mm beneath the peritoneum
      it is called deeply infiltrating endometriosis and may involve the bladder. Only
      1-2% of women with endometriosis have urinary involvement, mainly in the bladder.
      Resectoscopic transurethral resection alone is no longer recommended because of
      the surgical risks and recurrence. Usually surgeons prefer a laparotomy or
      laparoscopic approach depending on nodule localization and personal skill. We
      describe a new combined transurethral approach with Versapoint((r)) and
      laparoscopic technique in the management of bladder endometriosis and the 12
      month follow-up. METHODS: We performed a prospective observational study of 12
      women affected by symptomatic bladder endometriosis at the University Hospital of
      Padova. We utilized a transurethral approach using a 5.2-mm endoscope with a 0.6
      mm-diameter bipolar electrode (Gynecare Versapoint((r))). We delimited just the
      edges of the lesion via cystoscopy, penetrating transmurally at 3 or 9 o'clock
      without trespassing into the bladder peritoneum. Then, starting from the lateral
      bladder hole, we excised the lesion by laparoscopy with Harmonic ACE((r)). The
      bladder hole was repaired with a continuous 3-0 monofilament two-layer suture.
      RESULTS: Operating time ranged from 115 to 167 min and mean blood loss ranged
      from 10 to 200 ml. No conversion to laparotomy and no intraoperative
      complications occurred. No dysuria or hematuria were present at follow-up. There
      was one case of persistent suprapubic pelvic pain at the 12-month follow-up.
      CONCLUSIONS: A combined transurethral approach with Versapoint((r)) and
      laparoscopic treatment is a safe and easy technique for the management of bladder
      endometriosis, with low risks and good resolution of symptoms.

PMID- 22407154
TI  - A novel approach for the treatment of pelvic abscess: transrectal endoscopic
      drainage facilitated by transanal endoscopic microsurgery access.
AB  - BACKGROUND: Postoperative pelvic abscesses in patients submitted to colorectal
      surgery are challenging. The surgical approach may be too risky, and image-guided
      drainage often is difficult due to the complex anatomy of the pelvis. This
      article describes novel access for drainage of a pelvic collection using a
      minimally invasive natural orifice approach. METHODS: A 37 year-old man presented
      with sepsis due to a pelvic abscess during the second postoperative week after a
      Hartmann procedure due to perforated rectal cancer. Percutaneous drainage was
      determined by computed tomography to be unsuccessful, and another operation was
      considered to be hazardous. Because the pelvic fluid was very close to the rectal
      stump, transrectal drainage was planned. The rectal stump was opened using
      transanal endoscopic microsurgery (TEM) instruments. The endoscope was advanced
      through the TEM working channel and the rectal stump opening, accessing the
      abdominal cavity and pelvic collection. RESULTS: The pelvic collection was
      endoscopically drained and the local cavity washed with saline through the scope
      channel. A Foley catheter was placed in the rectal stump. The patient's recovery
      after the procedure was successful, without the need for further intervention.
      CONCLUSIONS: Transrectal endoscopic drainage may be an option for selected cases
      of pelvic fluid collection in patients submitted to Hartmann's procedure. The
      technique allows not only fluid drainage but also visualization of the local
      cavity, cleavage of multiloculated abscesses, and saline irrigation if necessary.
      The use of TEM instrumentation allows safe access to the peritoneal cavity.

PMID- 22407155
TI  - Churg-Strauss syndrome presenting with severe cutaneous and intestinal ulcers.

PMID- 22407156
TI  - 90Y PET-based dosimetry after selective internal radiotherapy treatments.
AB  - OBJECTIVES: The decay of 90Y has a minor branch to the O+ first excited state of
      89Zr, the de-excitation of which to the fundamental state is followed by a beta+
      beta- emission that has been used recently for biodistribution assessment after
      selective internal radiotherapy (SIRT) treatments. The purpose of the present
      study is to demonstrate the feasibility of 90Y PET imaging for dose assessment
      after radioembolization with 90Y microspheres. METHODS: Activity quantification
      was validated through preliminary phantom studies using a cylindrical body
      phantom composed of six inserts of different volumes filled with a calibrated
      amount of 90Y microspheres. A GE Discovery ST PET/CT scanner provided with
      bismuth germinate (BGO) crystals was used for image acquisition. Images were
      reconstructed with an ordered subset expectation-maximization method. The effect
      of object size and the effect of the number of iterations on dose evaluation and
      volume recovery were investigated. Microsphere dose distribution was then
      evaluated on one patient (one lesion) who underwent liver SIRT treatment. Dose
      calculations were made with a MATLAB-based code developed in our department.
      Dedicated Monte Carlo calculations were executed to evaluate dose S-values for
      the 90Y source. The activity distribution derived from 90Y PET acquisitions was
      convolved with the voxel S-values to obtain a three-dimensional absorbed dose
      distribution and dose-volume histograms. RESULTS: Dosimetry studies carried out
      on the body phantom with ordered subset expectation-maximization algorithm, three
      iterations, provided an accuracy of 7.62% in determining the absorbed dose in the
      largest insert. The dose difference increases as the insert size reduces.
      Preliminary results on a patient provided a high-resolution absorbed dose
      distribution map. An average dose of 139.3 Gy was evaluated for the tumor area,
      with a maximum dose as high as 237.9 Gy. The absorbed dose to the healthy liver
      was below the tolerance dose of 35 Gy (33.8 Gy). A clear correlation between
      absorbed dose and tumor response was observed at 18F-fluorodeoxyglucose PET
      acquired 6 months after treatment. CONCLUSION: According to our experience, 90Y
      PET is a promising and reliable technique for microsphere dose assessment and
      might pave the way for a patient-specific PET-based dosimetry after liver SIRT
      treatments.

PMID- 22407157
TI  - Postablative reconstruction of vulvar defects with local fasciocutaneous flaps
      and superficial fascial system repair.
AB  - INTRODUCTION: Postablative reconstruction of vulvar defects is a difficult
      challenge because of the functional, locational and cosmetic importance of this
      region. Local flaps carry a high incidence of delayed wound healing as local
      flaps may redistribute but not eliminate local wound tension. Repair of the
      superficial fascial system may avert local complications by minimising tension to
      the skin and increasing the initial biomechanical strength of wound. The aim of
      this study was to determine the clinical outcome of local fasciocutaneous flaps
      used for postablative reconstruction of vulvar defects in which the superficial
      fascial system was repaired. METHODS: A retrospective analysis was conducted of
      patients with vulvar carcinoma in situ or vulvar carcinoma, who underwent
      ablation and immediate reconstruction with local fasciocutaneous flaps and
      superficial fascial system repair. Postoperative complications were recorded and
      clinical outcomes were evaluated. RESULTS: Twelve of the 13 flaps healed
      primarily. Complications included 2 superficial wound infections, both of which
      were treated successfully with antibiotic therapy. One flap was complicated by
      minor wound dehiscence, which healed with conservative treatment. DISCUSSION:
      Local fasciocutaneous flaps with superficial fascial system repair provide
      excellent design flexibility and can be designed and tailored to reconstruct
      postablative vulvar defects with good outcomes and minimal morbidity.

PMID- 22407158
TI  - Retroperitoneal vascular aberrations increase the risk of vascular injury during
      lymphadenectomy in gynecologic cancers.
AB  - PURPOSE: To investigate the frequency of aberrations of retroperitoneal great
      vessels in patients with gynecologic cancers who were scheduled for pelvic and
      paraaortic lymphadenectomy, and to document the vascular complications which
      occurred during lymphadenectomy as well as the relationship of these vascular
      complications with vascular aberrations. METHODS: Patients with gynecologic
      cancers underwent a routine preoperative abdominal multi-detector computer
      tomography, and an intraoperative search for aberrations of the great vessels in
      the retroperitoneal region was undertaken. Intraoperative vascular complications
      were recorded and their relations to vascular aberrations were analyzed. RESULTS:
      The rate of vascular aberrations detected preoperatively by multi-detector
      computed tomography was 24.3 %. Vascular injuries occurred in six patients (16.2
      %) during lymphadenectomy. Rate of intraoperative vascular injuries was
      significantly higher in patients who had vascular aberrations of retroperitoneal
      great vessels (44.4 vs. 7.1 %, p = 0.022). CONCLUSIONS: Aberrations of
      retroperitoneal vessels are not uncommon and may increase the risk of vascular
      complications during lymphadenectomy. The risk of these complications may be
      decreased if aberrations are detected preoperatively.

PMID- 22407159
TI  - On-site chemical reaction lights up protein assemblies in cells.
AB  - Here we report a fast and effective method to visualize interactive proteins
      across intact mammalian cells via on-site formation of fluorescence using instant
      reaction of non-fluorescent fluorescamine with primary amines on proteins.
      Without interference by fluorescence background, this fluorogenic labelling opens
      a way for selective identification of primary amine-rich interacting proteins,
      efficient mapping and real-time monitoring of their spatial distribution in
      assemblies/network, and fast differentiation of cellular types. Without adverse
      effect on biological functions, this labelling method also provides new insights
      to comprehend important aspects of cellular functions of organelles and their
      relation to health imperfections for disease diagnostics and imaging-guided
      therapy.

PMID- 22407160
TI  - The uniform data system for medical rehabilitation: report of patients with
      traumatic spinal cord injury discharged from rehabilitation programs in 2002
      2010.
AB  - OBJECTIVE: This study aimed to provide benchmarking information from a large
      national sample of patients receiving inpatient rehabilitation after a traumatic
      spinal cord injury. DESIGN: This was an analysis of secondary data from 891
      inpatient medical rehabilitation facilities in the United States that contributed
      traumatic spinal cord injury data to the Uniform Data System for Medical
      Rehabilitation from January 2002 to December 2010. Variables analyzed included
      demographic information (age, sex, marital status, race/ethnicity, prehospital
      living setting, discharge setting), hospitalization information (length of stay,
      program interruptions, payer, onset date, rehabilitation impairment group,
      International Classification of Diseases 9 codes for admitting diagnosis, co
      morbidities), and functional status (Functional Independence Measure [FIM]
      instrument ratings at admission and discharge, FIM efficiency, FIM gain).
      RESULTS: The final sample included 47,153 patients with traumatic spinal cord
      injury. Overall, the mean length of stay was 26.2 +/- 23.2 days: yearly means
      ranged from 29.7 +/- 25.4 in 2002 to 22.9 +/- 18.9 in 2009. FIM total admission
      and discharge ratings also declined during the 8-yr study period; admission
      decreased from 60.5 +/- 17.4 to 55.9 +/- 16.3; discharge decreased from 86.1 +/-
      23.8 to 82.4 +/- 23.4. Rehabilitation efficiency (FIM gain per day) remained
      relatively stable over time (1.6 +/- 1.7 points per day). The percentage of all
      patients discharged to the community ranged from 75.8% to 71.5% per year.
      Wheelchair users stayed in rehabilitation longer than did persons who could walk
      (34.6 +/- 217.4 vs. 17.4 +/- 14.1 days) and also experienced less functional
      improvement (21.6 +/- 15.8 vs. 29.6 +/- 16.3 FIM points). CONCLUSIONS: National
      data from persons with traumatic spinal cord injury in 2002-2010 indicate that
      lengths of stay declined, but efficiency in functional independence was stable to
      slightly increased. More than 70% of patients were consistently discharged to
      community settings after inpatient rehabilitation.

PMID- 22407161
TI  - Weight bearing through lower limbs in a standing frame with and without arm
      support and low-magnitude whole-body vibration in men and women with complete
      motor paraplegia.
AB  - OBJECTIVE: The aim of the study was to determine the proportion of body weight
      borne through the lower limbs in persons with complete motor paraplegia using a
      standing frame, with and without the support of their arms. We also examined the
      effect of low-magnitude whole-body vibration on loads borne by the lower limbs.
      DESIGN: Vertical ground reaction forces (GRFs) were measured in 11 participants
      (six men and five women) with paraplegia of traumatic origin (injury level T3
      T12) standing on a low-magnitude vibrating plate using a standing frame. GRFs
      were measured in four conditions: (1) no vibration with arms on standing frame
      tray, (2) no vibration with arms at side, (3) vibration with arms on tray, and
      (4) vibration with arms at side. RESULTS: GRF with arms on tray, without
      vibration, was 0.76 +/- 0.07 body weight. With arms at the side, GRF increased to
      0.85 +/- 0.12 body weight. With vibration, mean GRF did not significantly differ
      from no-vibration conditions for either arm positions. Oscillation of GRF with
      vibration was significantly different from no-vibration conditions (P < 0.001)
      but similar in both arm positions. CONCLUSIONS: Men and women with paraplegia
      using a standing frame bear most of their weight through their lower limbs.
      Supporting their arms on the tray reduces the GRF by approximately 10% body
      weight. Low-magnitude vibration provided additional oscillation of the load
      bearing forces and was proportionally similar regardless of arm position.

PMID- 22407164
TI  - A NMR and computational study of Smac mimics targeting both the BIR2 and BIR3
      domains in XIAP protein.
AB  - In this paper we report an extensive NMR analysis of small ligands (Smac mimics)
      complexed with different constructs of XIAP. The mimics-binding site of XIAP is
      known as the BIR3 domain - primary, and the linker BIR2 region - secondary site.
      Interactions between the BIR3 domain and Smac mimics have been extensively
      studied by X-ray but, as of today, there are scarce data about the interaction
      between BIR2, or the whole linker-BIR2-BIR3 construct, and Smac mimics. In order
      to characterize our Smac mimics, we performed a STD NMR study between our 4
      substituted, 1-aza-2-oxobicyclo[5.3.0]decane scaffold-based molecules and three
      different XIAP fragments: single BIR2 and BIR3 domains, and bifunctional linker
      BIR2-BIR3. The results were integrated with docking calculations and molecular
      dynamics simulations. NMR data, which are consistent with biological tests,
      indicated that the two BIR subunits interact differently with our Smac mimics and
      suggest that the ligands enter into more intimate contact with the linker-BIR2
      BIR3. In conclusion, we observe that the SMAC mimics showed with the construct
      linker-BIR2-BIR3 a series of NOE contacts that were not observed in the mono
      domain ligand:BIR2 or :BIR3 complexes. So, in agreement with the computational
      models we believe that the linker moieties of the binding site play a key role in
      the stability of the protein complex.

PMID- 22407165
TI  - Fabrication of high performance surface enhanced Raman scattering substrates by a
      solid-state ionics method.
AB  - Silver nanostructures were prepared by a solid-state ionics method using fast
      ionic conductor RbAg(4)I(5) films under a direct current electric field (DCEF).
      The surface morphology of the silver nanostructures grown under different
      constant current fields was characterized by scanning electron microscopy (SEM).
      Rhodamine 6G (R6G) aqueous solutions were used as probe molecules to detect the
      Raman enhancement performance of the silver nanostructure substrates. The effect
      of external electric field current intensity on the surface morphology of the
      silver nanostructures during the preparation was studied in detail. The
      enhancement effect of the silver nanostructure surface enhanced Raman scattering
      (SERS) substrates with different surface morphologies toward R6G was determined.
      We found that disordered silver nanowires (DSNW), ordered silver nanowires
      (OSNW), densely arranged silver nanobamboo arrays (SNBA) and compactly arranged
      silver nanobud clusters (SNBC) were respectively obtained when the constant
      current intensity was 3 MUA, 5 MUA, 8 MUA and 12 MUA under the same vacuum
      evaporation plating conditions. The limiting concentrations of R6G for these SERS
      substrates were found to be 10(-7) mol l(-1), 10(-13) mol l(-1), 10(-13) mol l(
      1) and 10(-16) mol l(-1), respectively.

PMID- 22407166
TI  - Ghrelin signaling in heart remodeling of adult obese mice.
AB  - Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHS
      R), has been suggested to be associated to obesity, insulin secretion,
      cardiovascular growth and homeostasis. GHS-R has been found in most of the
      tissues, and among the hormone action it is included the regulation of heart
      energy metabolism. Therefore, hypernutrition during early life leads to obesity,
      induces cardiac hypertrophy, compromises myocardial function, inducing heart
      failure in adulthood. We examined ghrelin signaling process in cardiac remodeling
      in these obese adult mice. The cardiomyocytes (cmy) of left ventricle were
      analyzed by light microscopy and stereology, content and phosphorilation of
      cardiac proteins: ghrelin receptor (growth hormone secretagogue receptor 1a, GHSR
      1a), protein kinase B (AKT and pAKT), phosphatidil inositol 3 kinase (PI3K), AMP
      activated protein kinase (AMPK and pAMPK) and actin were achieved by Western
      blotting. GHSR-1a gene expression was analyzed by Real Time-PCR. We observed
      hyperglycemia and higher liver and visceral fat weight in obese when compared to
      control group. Obese mice presented a marked increase in heart weight/tibia
      length, indicating an enlarged heart size or a remodeling process. Obese mice had
      increased GHSR-1a content and expression in the heart associated to PI3K content
      and increased AKT content and phosphorylation. In contrast, AMPK content and
      phosphorylation in heart was not different between experimental groups. Ghrelin
      plasma levels in obese group were decreased when compared to control group. Our
      data suggest that remodeled myocardial in adult obese mice overnourished in early
      life are associated with higher phosphorylation of GHSR-1a, PI3K and AKT but not
      with AMPK.

PMID- 22407167
TI  - Platycodi Radix suppresses development of atopic dermatitis-like skin lesions.
AB  - Platycodi Radix has been used to treat chronic diseases, such as bronchitis,
      asthma, and hyperlipidemia. In this study, we examined the effect of an aqueous
      extract, Changkil (CK), from the root of Platycodi Radix on 2,4
      dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions.
      Administration of CK onto DNCB-induced AD-like skin lesions in NC/Nga mice
      ameliorated lesion intensity scores, levels of IgE, thymus and activation
      regulated chemokine (TARC), TNF-alpha, and IL-4 in serum and ears. In contrast,
      CK increased level of the immunosuppressive cytokine IL-10. Histopathological
      examination showed reduced thickness of the epidermis/dermis and dermal
      infiltration of inflammatory cells in the ears. CK also suppressed TNF-alpha/IFN
      gamma-induced mRNA expression and production of TARC in HaCaT cells. CK exerts
      beneficial effects on AD symptoms, suggesting that CK is an effective potential
      therapeutic agent for AD.

PMID- 22407168
TI  - The impaired disposition of probe drugs is due to both liver and kidney
      dysfunctions in CCl(4)-model rats.
AB  - The carbon tetrachloride (CCl(4))-treated model involving mature Sprague-Dawley
      rats has been historically relied upon to study liver injury and regeneration and
      to test drug efficacy and disposition. However, there few studies about phase II
      metabolic enzymes changes in CCl(4)-model rats. The metabolic and excretion tests
      of phenacetin and acetaminophen (APAP), and the mRNA test of cytochrome P4501A2
      (CYP1A2) and phase II metabolic enzymes [sulfotransferase 1A1 (SULT1A1) and UDP
      glucuronosyltransferase 1A6 (UGT1A6)] were studied in model rats after CCl(4)
      pretreatment. The result showed that the function and structure of liver and
      kidney was impaired by CCl(4) pretreatment, and a significant difference has been
      observed in the mRNA content of CYP1A2 (p<0.01) in model group, but there was no
      significant difference on the mRNA content of SULT1A1 and UGT1A6 in both groups.
      Compared to the control group, a significant higher content of phenacetin
      (p<0.01) and sulfate-APAP (AS, p<0.01) was observed in the metabolic tests of
      phenacetin and APAP. Statistically significant differences in cumulative urinary
      excretion levels of APAP, AG and AS for CCl(4) model rats were observed also. We
      have shown that impaired disposition of probe drugs in this model was due to both
      liver and kidney dysfunction in CCl(4)-model rats and we should consider the
      development of a new liver damage model without renal impairment.

PMID- 22407169
TI  - A new biological test utilising the yeast Saccharomyces cerevisiae for the rapid
      detection of toxic substances in water.
AB  - This study evaluates the toxic effects of five substances (atropine,
      fenitrothion, potassium cyanide, mercuric chloride and lead nitrate) on the yeast
      Saccharomyces cerevisiae. It describes a new biological toxicity test based on
      inhibition of S. cerevisiae viability and compares it with two standard toxicity
      tests based on Daphnia magna mobility inhibition (EN ISO 6341) and Vibrio
      fischeri bioluminiscence inhibition (EN ISO 11348-2). The new biological test -S.
      cerevisiae lethal test - is cheaper and 24 times faster than the D. magna test.
      The test speed is comparable with the V. fischeri test but the new test is more
      sensitive for some substances. The test indicates reliably the presence of all
      used toxicants in water in concentrations which are significantly lower than the
      concentration in toxic or lethal doses for man. Therefore, this new toxicity test
      could be proposed for rapid detection of toxic substances in water.

PMID- 22407170
TI  - Single-nucleotide polymorphisms in HORMAD1 may be a risk factor for azoospermia
      caused by meiotic arrest in Japanese patients.
AB  - Genetic mechanisms are implicated as a cause of some male infertility, yet are
      poorly understood. Meiosis is unique to germ cells and essential for
      reproduction. The synaptonemal complex is a critical component for chromosome
      pairing, segregation and recombination. Hormad1 is essential for mammalian
      gametogenesis as knockout male mice are infertile. Hormad1-deficient testes
      exhibit meiotic arrest in the early pachytene stage and synaptonemal complexes
      cannot be visualized. To analyze the hypothesis that the human HORMAD1 gene
      defects are associated with human azoospermia caused by meiotic arrest,
      mutational analysis was performed in all coding regions by direct sequence
      analysis of 30 Japanese men diagnosed with azoospermia resulting from meiotic
      arrest. By the sequence analysis, three polymorphism sites, Single Nucleotide
      Polymorphism 1 (c. 163A>G), SNP2 (c. 501T>G) and SNP3 (c. 918C>T), were found in
      exons 3, 8 and 10. The 30 patients with azoospermia and 80 normal pregnancy
      proven, fertile men were analyzed for HORMAD1 polymorphisms. Both SNP1 and SNP2
      were associated with human azoospermia caused by complete early meiotic arrest
      (P<0.05). We suggest that the HORMAD1 has an essential meiotic function in human
      spermatogenesis.

PMID- 22407171
TI  - Effect of chronic CPT-1 inhibition on myocardial ischemia-reperfusion injury
      (I/R) in a model of diet-induced obesity.
AB  - PURPOSE: By increasing circulating free fatty acids and the rate of fatty acid
      oxidation, obesity decreases glucose oxidation and myocardial tolerance to
      ischemia. Partial inhibition of fatty acid oxidation may improve myocardial
      tolerance to ischemia/reperfusion (I/R) in obesity. We assessed the effects of
      oxfenicine treatment on post ischemic cardiac function and myocardial infarct
      size in obese rats. METHODS: Male Wistar rats were fed a control diet or a high
      calorie diet which resulted in diet induced obesity (DIO) for 16 weeks.
      Oxfenicine (200 mg/kg/day) was administered to control and DIO rats for the last
      8 weeks. Isolated hearts were perfused and infarct size and post ischemic cardiac
      function was assessed after regional or global ischemia and reperfusion. Cardiac
      mitochondrial function was assessed and myocardial expression and activity of CPT
      1 (carnitine palmitoyl transferase-1) and IRS-1 (insulin receptor substrate-1)
      was assessed using Western blot analysis. RESULTS: In the DIO rats, chronic
      oxfenicine treatment improved post ischemic cardiac function and reduced
      myocardial infarct size after I/R but had no effect on the cardiac mitochondrial
      respiration. Chronic oxfenicine treatment worsened post ischemic cardiac
      function, myocardial infarct size and basal mitochondrial respiration in control
      rat hearts. Basal respiratory control index (RCI) values, state 2 and state 4
      respiration rates and ADP phosphorylation rates were compromised by oxfenicine
      treatment. CONCLUSION: Chronic oxfenicine treatment improved myocardial tolerance
      to I/R in the obese rat hearts but decreased myocardial tolerance to I/R in
      control rat hearts. This decreased tolerance to ischemia of oxfenicine treated
      controls was associated with adverse changes in basal and reoxygenation
      mitochondrial function. These changes were absent in oxfenicine treated hearts
      from obese rats.

PMID- 22407172
TI  - Group sequential control of overall toxicity incidents in clinical trials - non
      Bayesian and Bayesian approaches.
AB  - In some small clinical trials, toxicity is not a primary endpoint; however, it
      often has dire effects on patients' quality of life and is even life-threatening.
      For such clinical trials, rigorous control of the overall incidence of adverse
      events is desirable, while simultaneously collecting safety information. In this
      article, we propose group sequential toxicity monitoring strategies to control
      overall toxicity incidents below a certain level as opposed to performing
      hypothesis testing, which can be incorporated into an existing study design based
      on the primary endpoint. We consider two sequential methods: a non-Bayesian
      approach in which stopping rules are obtained based on the 'future' probability
      of an excessive toxicity rate; and a Bayesian adaptation modifying the proposed
      non-Bayesian approach, which can use the information obtained at interim
      analyses. Through an extensive Monte Carlo study, we show that the Bayesian
      approach often provides better control of the overall toxicity rate than the non
      Bayesian approach. We also investigate adequate toxicity estimation after the
      studies. We demonstrate the applicability of our proposed methods in controlling
      the symptomatic intracranial hemorrhage rate for treating acute ischemic stroke
      patients. 

PMID- 22407174
TI  - Impact of antiepileptic drugs on thrombocytopenia in glioblastoma patients
      treated with standard chemoradiotherapy.
AB  - Epilepsy in glioblastoma multiforme (GBM) patients is common. Hematological
      toxicity is a potential side effect of antiepileptic drugs (AEDs) and a frequent
      limiting-dose effect of temozolomide (TMZ). The aim of the study was to
      investigate the impact of AEDs on thrombocytopenia in GBM patients treated with
      radiotherapy and TMZ. A cohort of 101 newly diagnosed GBM patients treated with
      radiotherapy and TMZ was reviewed. Clinical data, presence of seizures, AEDs use,
      platelet count, and accumulated TMZ dose were analyzed at each cycle.
      Thrombocytopenia was operationalized as a continuous platelet count and a
      dichotomic variable (cut-off <100.000/mm(3)). This cut-off represents the
      threshold beyond which TMZ treatment is modified. A linear and a probit pooled
      cross-sectional regression analysis were used to study the impact of age, gender,
      AEDs, and accumulated TMZ on thrombocytopenia. Impact of AEDs on survival was
      also analyzed. Thirty-five patients (35%) presented seizures at onset and 18
      (27%) during follow-up. Seven (13%) needed two or more AEDs for seizure control.
      Grade 3-4 thrombocytopenia was found in 8%. Decrease in platelet count was
      related to accumulated TMZ (p < 0.001), age (p < 0.001), and valproate (p =
      0.004). Platelet count <100.000/mm(3) was only associated with accumulated TMZ (p
      = 0.001). Recursive Partitioning Analysis prognostic class was the only variable
      with significant impact on survival. Valproate and age had an independent
      negative effect on total platelet count, although neither had an effect on
      critical thrombocytopenia (<100.000/mm(3)). Therefore, the systematic withhold of
      valproate in GBM patients might not be justified. Nevertheless, this negative
      effect may be taken into account especially in elderly patients.

PMID- 22407175
TI  - Assessment of intra-observer variability in measurement of high-grade brain
      tumors.
AB  - A 25% increase in bidimensional products (BPs) of tumor diameter has been used as
      a criterion for brain tumor progression. We studied intra-observer variability in
      measurements of BPs. Ten patients with contrast-enhancing glioblastoma multiforme
      underwent baseline and follow-up MR imaging. Seven observers measured BPs in
      various planes. Differences in BPs between scans were expressed as a percentage
      of baseline. This calculation was performed for both readings of the baseline and
      follow-up scans. Differences between change from baseline to follow-up on each
      reading (termed D values) were calculated for each reader (total of 196 D
      values). Median D value in each plane was calculated for each reader. Range of D
      values was 12.36-33.64% in axial plane (average 10.63%), 12.18-38.62% in coronal
      plane (average 26.84%) and 15.12-35.48% in sagittal plane (average 26.11%).
      Across all planes, 88 (45%) D values were >25%. When all imaging planes for any
      single observation were combined, in 76% of cases, at least one D value of >25%
      was seen. Based on the high degree of intra-observer variability, tumor
      measurements producing an increase in BP of >25% can routinely be obtained solely
      by chance.

PMID- 22407176
TI  - Development of a novel animal model to differentiate radiation necrosis from
      tumor recurrence.
AB  - Distinguishing tumor progression from radiation necrosis after treatment in
      patients with brain tumors presents a clinical dilemma. A well-characterized,
      orthotopic rodent model of radiation-induced brain necrosis including a tumor is
      not currently available The objective of the study was to create focal radiation
      necrosis in rat brain bearing human glioblastoma (GBM) using stereotactic
      radiosurgery and confirm it by immuno-histological analysis. Nude rats implanted
      with primary GBM cells were irradiated using a stereotactic setup (n = 3) or
      received no radiation (n = 3). Ten weeks after the implantation, growth of the
      tumor was confirmed by magnetic resonance imaging (MRI). For each animal, MRI and
      contrast-enhanced CT images were obtained and fused using registration software.
      The tumor was identified and delineated using the fused CT/MR images. A treatment
      plan was generated using a 4 mm radiosurgery cone such that one portion of the
      tumor receives 100% dose of 60 Gy sufficient to cause necrosis, whereas the tumor
      edge at depth receives only 50% or less dose, allowing for regrowth of the tumor.
      The brains were collected 10 weeks after irradiation and immuno-histological
      analysis was performed. Hematoxylin and eosin staining showed central
      liquefaction necrosis in the high dose region consistent with necrosis and viable
      tumor in the peripheral low dose region. Ki-67 staining showed highly
      proliferative tumor cells surrounding the necrotic parts of the tumor. Luxol fast
      blue and lectin staining showed demyelination and vascular injury in brain tissue
      consistent with radiation necrosis. We have developed a novel model of radiation
      necrosis in rats bearing glioma.

PMID- 22407177
TI  - Phase 1 trial of dasatinib plus erlotinib in adults with recurrent malignant
      glioma.
AB  - To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of
      dasatinib, an inhibitor of the Src family kinase proteins, with erlotinib, an
      epidermal growth factor receptor tyrosine kinase inhibitor, among recurrent
      malignant glioma patients. Once daily dasatinib was escalated in successive
      cohorts while erlotinib was administered daily at established doses based on
      concurrent CYP3A-inducing anticonvulsant (EIAEDS) use. Dasatinib pharmacokinetic
      analyzes were performed. Forty-seven patients enrolled including 37 (79 %) with
      grade IV and 10 (21 %) with grade III malignant glioma. Thirty patients (64 %)
      were at >=second recurrence, while 27 (57 %) had received prior bevacizumab. The
      dasatinib MTD was 180 mg when combined with either 150 mg of erlotinib for
      patients not on EIAEDs, or 450 mg of erlotinib for patients on EIAEDs. The most
      common DLTs were diarrhea and fatigue, while most adverse events were grade 2.
      Pharmacokinetic data suggests that dasatinib exposure increased with increased
      dasatinib dose and concurrent erlotinib administration, while concurrent EIAED
      use diminished dasatinib exposure. No radiographic responses were observed, and
      only one patient (2 %) remained progression-free at 6 months. We demonstrate that
      dasatinib plus erlotinib can be safely co-administered on a continuous, daily
      dosing schedule with erlotinib, and established the recommended dose level of
      this combination.

PMID- 22407178
TI  - Pulse oximeter plethysmograph variation and its relationship to the arterial
      waveform in mechanically ventilated children.
AB  - The variations induced by mechanical ventilation in the arterial pulse pressure
      and pulse oximeter plethysmograph waveforms have been shown to correlate closely
      and be effective in adults as markers of volume responsiveness. The aims of our
      study were to investigate: (1) the feasibility of recording plethysmograph
      indices; and (2) the relationship between pulse pressure variation (DeltaPP),
      plethysmograph variation (DeltaPOP) and plethysmograph variability index (PVI) in
      a diverse group of mechanically ventilated children. A prospective, observational
      study was performed. Mechanically ventilated children less than 11 years of age,
      with arterial catheters, were enrolled during the course of their clinical care
      in the operating room or in the pediatric intensive care unit. Real time monitor
      waveforms and trend data were recorded. DeltaPP and DeltaPOP were manually
      calculated and the relationships between DeltaPP, DeltaPOP and PVI were compared
      using Bland-Altman analysis and Pearson correlations. Forty-nine children were
      recruited; four (8%) subjects were excluded due to poor quality of the
      plethysmograph waveforms. DeltaPP and DeltaPOP demonstrated a strong correlation
      (r = 0.8439, P < 0.0001) and close agreement (Bias = 1.44 +/- 6.4%). PVI was
      found to correlate strongly with DeltaPP (r = 0.7049, P < 0.0001) and DeltaPOP (r
      = 0.715, P < 0.0001). This study demonstrates the feasibility of obtaining
      plethysmographic variability indices in children under various physiological
      stresses. These data show a similarly strong correlation to that described in
      adults, between the variations induced by mechanical ventilation in arterial
      pulse pressure and the pulse oximeter plethysmograph.

PMID- 22407181
TI  - An arthroscopic pleated capsular shift for recurrent anterior dislocation of the
      shoulder.
AB  - PURPOSE: This study examined the clinical results of an arthroscopic simple
      pleated capsular shift to treat severe recurrent anterior dislocation of the
      shoulder. METHODS: Twenty-four patients with anterior labroligamentous periosteal
      sleeve avulsion or advanced lesions who underwent an arthroscopic simple pleated
      capsular shift were included in this study. To create an arthroscopic simple
      pleated capsular shift, redundant capsules, including glenohumeral ligaments,
      were brought at least 1 cm lateral and 1 cm inferior and shifted to the prepared
      glenoid. Four sutures were made at the 5, 4, 3, and 1-2 o'clock positions with
      four anchors. Clinical results were evaluated using a visual analog scale (VAS),
      ROWE scores, active motion, and return to activity. Statistical analyses were
      carried out using paired t tests. RESULTS: Three out of 24 patients had
      complaints. Two patients with recurrent instability underwent a repeat surgery,
      while the other patient complained of a stiff shoulder. There was a significant
      improvement in the VAS and ROWE scores post-operatively versus pre-operatively (p
      < 0.001, p < 0.001, respectively), but no significant differences in active
      motion except for external rotation, which decreased post-operatively (p = 0.02).
      CONCLUSIONS: In patients with severe recurrent anterior dislocation, simple
      pleated capsular shift provided a reliable result. Four capsular shift sutures, 1
      cm lateral and 1 cm inferior from the glenoid, were sufficient to reduce shoulder
      joint volume and restore stability. The arthroscopic capsular shift could be an
      alternative method in the case of no available labral lesion for repair. LEVEL OF
      EVIDENCE: Case series, Therapeutic, Level IV.

PMID- 22407179
TI  - A possible relationship between reliability of thoracic outlet syndrome
      diagnostic testing and the position of the axillary artery.
AB  - PURPOSE: Publications describe variable spatial relationships between the
      axillary artery and brachial plexus whereby the axillary artery may be compressed
      by the median nerve roots when the upper extremity is hyper-abducted. The purpose
      of this study is to quantify the frequency of variant positioning of the axillary
      artery with respect to the brachial plexus, describe and quantify the lengths of
      the median nerve roots, and evaluate intra-arterial pressure in axillary arteries
      of normal and variant cadavers when the upper extremity is hyper-abducted.
      METHODS: Three-hundred and thirty-eight cadaveric axillae were dissected to
      evaluate the spatial relationship between axillary artery and the median nerve
      roots. Three-hundred and twelve cadaveric axillae were dissected to evaluate the
      lengths of the median nerve roots. Twelve cadavers were selected for evaluation
      of the intra-arterial pressure during a hyper-abduction procedure. RESULTS: The
      axillary artery was positioned anterior to the median nerve roots in 6.8% of
      axillae and positioned posterior to the median nerve roots in 93.2% of axillae.
      An experimental cohort, possessing a classic relationship between axillary artery
      and median nerve roots and a proximal union of the median nerve roots, showed an
      increase in intra-arterial pressure during hyper-abduction test. All other
      experimental cohorts exhibited no change in intra-arterial pressure. CONCLUSIONS:
      These findings suggest that the median nerve roots are capable of compressing the
      axillary artery when the upper extremity is hyper-abducted, the axillary artery
      is positioned posterior to the median nerve roots, and the patient possesses a
      more proximal convergence of the median nerve roots.

PMID- 22407182
TI  - Long-term follow-up of patellar tendon grafts or hamstring tendon grafts in
      endoscopic ACL reconstructions.
AB  - PURPOSE: Several studies compare the short- and long-term results of anterior
      cruciate ligament (ACL) reconstruction using bone-patellar tendon-bone (BPTB)
      graft or double-looped semitendinosus and gracilis (DLSG) graft. However, no
      studies evaluate the long-term results of BPTB grafts fixed with metal
      interference screws and DLSG grafts fixed with the Bone Mulch Screw and the
      Washer Loc. This prospective randomized multicentre study has the null hypothesis
      that there is no difference in long-term outcome between the two procedures.
      METHODS: A total of 114 patients with a symptomatic ACL rupture were randomized
      to reconstruction with either a BPTB graft (N = 58) or a DLSG graft (N = 56).
      Follow-up was conducted after one, two and seven years. At the seven-year follow
      up, 102 of the 114 patients (89%) were available for evaluation; however, 16 of
      these by telephone-interview only. RESULTS: Ten patients in the BPTB group and 19
      patients in the DLSG group underwent additional knee surgery (P = 0.048), two and
      three, respectively, of these were ACL revisions (n.s.). The total flexion work
      was lower in the DLSG group (P = 0.001). The mean peak flexion torque and
      extension work, however, showed no difference between the groups. No significant
      differences were found between the groups regarding the Tegner activity score,
      the Lysholm functional score, the Knee injury and osteoarthritis outcome score
      (KOOS), subjective knee function, anterior knee pain or mobility. There was no
      significant difference in laxity between the groups on the Lachman test or the KT
      1,000 maximum manual force test. CONCLUSIONS: Both grafts and fixation methods
      resulted in satisfactory subjective outcome and objective stability. Both these
      methods can therefore be considered as suitable alternatives for ACL
      reconstructions. LEVEL OF EVIDENCE: II.

PMID- 22407183
TI  - Patellofemoral arthroplasty, where are we today?
AB  - PURPOSE: Patellofemoral arthroplasty remains controversial, primarily due to the
      high failure rates reported with early implants. Numerous case series have been
      published over the years detailing results of various first- and second
      generation implants. The purpose of this work is to summarize results published
      to date and identify common themes regarding implants, surgical techniques, and
      indications in order to maximize results of future procedures. METHODS: A
      comprehensive review of the MEDLINE database was carried out to identify all
      clinical studies related to patellofemoral arthroplasty. RESULTS: First
      generation resurfacing implants were associated with relatively high failure
      rates in the medium term. Second-generation implants, with femoral cuts based on
      TKA designs have yielded more promising medium-term results. Surgical indications
      are specific and must be carefully followed to minimize poor results. Short-term
      complications are generally related to patellar maltracking, while long-term
      complications are generally related to progression of osteoarthritis in the
      tibiofemoral joint. Implant loosening and polyethylene wear are rarely reported.
      Short-term results are favourable for new technology including custom implants
      and computer navigated surgery. CONCLUSIONS: Overall, recent improvements in
      implant design and surgical techniques have resulted in improvements in short-
      and medium-term results. More work is required to assess the long-term outcomes
      of modern implant designs. LEVEL OF EVIDENCE: IV.

PMID- 22407184
TI  - Size comparison of ACL footprint and reconstructed auto graft.
AB  - PURPOSE: The purpose of this study was to compare the size of native anterior
      cruciate ligament (ACL) footprints and the size of commonly used auto grafts. The
      hypothesis was that the reconstructed graft size with auto grafts might be
      smaller than the native ACL footprint. METHODS: Fourteen non-paired human cadaver
      knees were used. The semitendinosus tendon (ST) and the gracilis (G) tendon were
      harvested and prepared for ACL grafts. Simulating an ST graft, the ST was cut in
      half. The bigger half was regarded as the antero-medial (AM) bundle, and the
      remaining half was regarded as the postero-lateral (PL) bundle. Simulating an ST
      G graft, the bigger half of the ST and G were regarded as the AM bundle, and the
      smaller half of the ST was regarded as the PL bundle. Each graft diameter was
      measured, and the graft area was calculated. Simulating a rectangular bone
      patella tendon-bone (BPTB) graft, a 10-mm wide BPTB graft was harvested and the
      area calculated. The ACL was carefully dissected, and the size of the femoral and
      tibial footprints was measured using Image J software (National Institution of
      Health). RESULTS: The average areas of the ST, ST-G, and BPTB graft were 52.3 +/-
      7.3, 64.4 +/- 9.2, and 32.7 +/- 6.5 mm(2), respectively. The sizes of the native
      femoral and tibial ACL footprints were 85.4 +/- 26.3 and 145.4 +/- 39.8 mm(2),
      respectively. Only the ST-G graft showed no significant difference in graft size
      when compared with the femoral ACL footprint. CONCLUSION: Only the ST-G auto
      graft was able to reproduce the native size of the ACL footprint on the femoral
      side. None of the auto grafts could reproduce the size of the tibial ACL
      footprint. For clinical relevance, ST-G graft is recommended in order to
      reproduce the native size of the ACL in anatomical ACL reconstruction with auto
      graft.

PMID- 22407185
TI  - Enhanced external counterpulsation for ischemic heart disease:  a look behind the
      curtain.
AB  - Enhanced external counterpulsation (EECP) is a noninvasive treatment for patients
      with coronary artery disease who have angina pectoris that is refractory to
      pharmacotherapy and revascularization. The popular concept is that EECP may
      promote collateral development and improve myocardial perfusion. We hypothesize
      that improvements in peripheral arterial function are responsible for the
      clinical benefits of EECP.

PMID- 22407186
TI  - Expression of high-risk HPV DNA and CK19 in pelvic lymph nodes in stage Ia-IIa
      cervical cancer and their clinical value.
AB  - The aim of this study was to investigate the detection rate and methods of
      micrometastases in early-stage cervical cancer by detecting the expression of
      high-risk HPV DNA and CK19 in pelvic lymph nodes. A total of 104 lymph nodes
      with/without pathologically confirmed metastases, from 28 patients with early
      stage cervical cancer, were included for detection of high-risk HPV DNA and CK19
      expression using in situ hybridization and immunohistochemistry, respectively.
      The detection rate of high-risk HPV DNA and CK19 in lymph nodes in patients with
      pathologically-confirmed lymph node metastases was higher compared to that in
      lymph nodes in patients without pathologically-confirmed lymph node metastases
      (P<0.001). In all 80 pathologically-negative lymph nodes, the positivity rates of
      high-risk HPV DNA and CK19 detection were 45 and 25%, respectively. In 57 lymph
      nodes in patients without pathologically-confirmed lymph node metastases the
      positivity rates of high-risk HPV DNA and CK19 detection were 43.5 and 24.6%. The
      detection rate of high-risk HPV DNA and CDK19 in 15 patients without
      pathologically-confirmed lymph node metastases were 60 and 46.6%, respectively.
      The detection rates of high-risk HPV DNA and CK19 in 104 lymph nodes were 56.7
      and 41.3% (KI=0.46). The results of the two detection methods showed good
      consistency. Both detection of high-risk HPV DNA by in situ hybridization, and
      CK19 by immunohistochemical method detected lymph node micrometastases in early
      stage cervical cancer. As a method of detection on the molecular level, in situ
      hybridization was more sensitive for the detection of lymph node micrometastases
      in early-stage cervical cancer.

PMID- 22407187
TI  - Commentary on: cutaneous amyloidoses and systemic amyloidoses with cutaneous
      involvement (Eur J Dermatol 2010; 20: 152-60).

PMID- 22407188
TI  - Quality of life of patients with asthma related to damp and moldy work
      environments.
AB  - OBJECTIVE: Long-term outcomes of asthma related to exposure to workplace dampness
      are not well known. The aim of this study was to evaluate the quality of life
      (QOL) of patients with asthma related to damp and moldy workplaces and
      characterize factors influencing QOL. METHODS: Using a questionnaire, we followed
      1267 patients previously examined for suspected occupational respiratory disease
      related to exposure to damp and moldy indoor environments. In addition to
      demographic and other background data, the questionnaire included sections on
      current employment status, QOL, anxiety and depression, somatization,
      hypochondria, and asthma medication. We compared the QOL of patients with
      occupational asthma (OA) with that of patients with work-exacerbated asthma (WEA)
      or symptoms without asthma. RESULTS: Impaired QOL was found among patients
      diagnosed with OA when they were compared with patients in corresponding
      environments with WEA or symptoms only. Not working and greater use of asthma
      medication were major determinants of worse QOL. Psychological factors did not
      explain the differences between the groups. CONCLUSIONS: OA induced by exposure
      to workplace moisture and molds is associated with QOL deterioration. The
      impairment is related to being unemployed (due to disability, retirement, job
      loss or other reasons) and the need for medication.

PMID- 22407189
TI  - Histological evaluation of rat larynx in experimental polycystic ovary syndrome
      model.
AB  - This study aimed at studying the histopathological effects of hyperandrogenemia
      and estrogen deficiency on larynx mucosa in experimentally designed polycystic
      ovary syndrome of female rats. Two groups of experimental polycystic ovary
      syndrome model were composed in healthy female rats by per oral letrozole
      administration of for 21 and 42 days. Also a control group which only took
      vehicle (saline) for 42 days was designed. Laryngeal mucosa and ovaries of all
      animals were examined histopathologically by light microscopy and the serum
      hormone levels were analyzed using a solid-phase, two-site chemiluminescent
      enzyme immunometric assay. Statistically significant edema, vascular engorgement,
      inflammation, cilia loss and differentiation of goblet cell distribution were
      observed when the control group and study groups were compared (p < 0.01). In
      serum hormonal analysis there was a significant increase in levels of androgens
      and decrease in levels of estrogens. In addition, polycystic appearance of
      ovaries in letrozole-administered groups and normal appearance of ovaries in
      control group have been proven histopathologically. Polycystic ovary syndrome
      which causes estrogen deficiency and hyperandrogenemia in fertile ages resulted
      in histopathological changes in laryngeal mucosa.

PMID- 22407190
TI  - The value of PET/CT to assess clinically negative necks.

PMID- 22407191
TI  - Study of clinical treatment of esophageal foreign body-induced esophageal
      perforation with lethal complications.
AB  - Esophageal foreign body-induced esophageal perforation is a lethal complication
      and its treatment very complex. We had reviewed 1,428 patients with esophageal
      foreign body, who were hospitalized and treated over the past 25 years. A
      classification summary was made of 121 patients (of these 1,428 cases) who
      presented with esophageal foreign body-induced perforation and complicated
      cervical abscess, mediastinitis, and mediastinal abscess. This summary considered
      foreign body types, location and lodging duration, complications, and surgical
      approaches. Among these 121 patients, esophageal foreign bodies in 81 patients
      were successfully extracted via esophagoscope or fiber optic esophagoscope.
      Cervical esophageal foreign bodies in 22 patients were extracted by esophagoscope
      and lateral cervical incision (n = 6) and simple lateral cervical incision (n =
      16). Thoracotomy was performed to remove thoracic esophageal foreign bodies in 18
      patients with 10 successes and 8 failures. Of the 121 patients, 67 patients with
      cervical abscess were cured by means of lateral cervical abscess incision and
      drainage, esophageal stent placement, and esophageal perforation repair with
      pedicle myolemma or pedicle muscular periosteum flap. 54 patients with
      mediastinitis and/or abscess were all cured, except one mortality, by means of
      mediastinotomy and drainage or/and closed-chest drainage, simple esophageal
      repair, esophageal repair with pedicle myolemma or pedicle muscular periosteum
      flap and stent placement for esophageal perforation, and esophageal exclusion
      plus two-stage gastric-pharyngeal anastomosis. In the treatment of esophageal
      foreign body-induced severe complications, various therapies should be applied
      simultaneously. Lateral cervical incision should be made immediately to remove
      the foreign bodies if the foreign body extraction under esophagoscope proves to
      be a failure after repeated attempts, or esophageal perforation develops during
      the procedure, or should cervical abscess develop. Mediastinotomy and drainage
      or/and closed-chest drainage should be carried out as early as possible when
      mediastinitis and/or mediastinal abscess develops after esophageal foreign body
      ingestion.

PMID- 22407192
TI  - The clinical role of critical pathway implementation for pancreaticoduodenectomy
      in 179 patients.
AB  - BACKGROUND/PURPOSE: In June 2004, a critical pathway for patients undergoing
      pancreaticoduodenectomy (PD) was introduced. The objective of this study was to
      determine the clinical value of critical pathway implementation. METHODS: 256
      consecutive patients who underwent PD between 2000 and 2010 were divided into 4
      groups by date of operation as follows; group A (n = 77), the pre-pathway group;
      group B (n = 51), the CP implementation group who were managed according to
      departmental guidelines; group C (n = 78), the group who had no stenting in the
      reconstruction of PD; and group D (n = 50), the group who had reinforcement of
      the pancreaticojejunostomy. The success rates of clinical outcomes and post
      operative morbidity were compared between each group, year by year and every 50
      patients. RESULTS: The success rates of clinical outcomes, including the timings
      of nasogastric tube removal, discontinuation of prophylactic anti-microbial
      agent, drain removal, starting oral intake, and patient discharge, were
      significantly improved in group B relative to group A, and in group C relative to
      group B. There were no significant differences in mortality and morbidity between
      any of the groups. All clinical outcomes reached a plateau at 2-3 years or 100
      150 patients' operations after critical pathway implementation. CONCLUSIONS: Long
      term use of a critical pathway is associated with improved clinical outcomes. A
      certain period of time or volume of patients is needed for this improvement in
      clinical outcomes to reach a plateau, which indicates achieving standardization
      of peri-operative management.

PMID- 22407193
TI  - Living donor liver transplantation for patients immunized against human leukocyte
      antigen.
AB  - BACKGROUND/PURPOSE: The clinical features and perioperative management of liver
      transplant recipients who are already sensitized against human leukocyte antigen
      (HLA) prior to transplantation are not yet clear. MATERIALS AND METHODS: Medical
      records of living donor liver transplant recipients were reviewed and clinical
      features of the patients possessing anti-HLA antibodies were studied. RESULTS:
      Among the 470 consecutive living donor liver transplant recipients, 6 patients
      (1.3%) had preformed anti-HLA antibodies. A review of the postoperative courses
      of these patients revealed that the problems included platelet transfusion
      refractoriness (PTR) due to immune-mediated destruction of platelet and
      thrombotic microangiopathy (TMA). PTR was observed in patients with anti-HLA
      class I antibodies and only HLA-matched platelet concentrate (HLA-matched PC)
      relieved thrombocytopenia. Intravenous gammaglobulin had an additive effect to
      HLA-matched PC in some cases, and platelet transfusion from close relatives might
      be a substitute for HLA-matched PC in life-threatening situations. Although the
      etiology of TMA is unremarkable, the incidence was high (67%, 4/6) compared with
      that in patients who were not sensitized against HLA (5.6%, 26/464; p < 0.01). Of
      the four patients, three were complicated with late-onset TMA. CONCLUSIONS:
      Considering these clinical features, careful preparation and postoperative
      management are needed for liver transplant candidates with anti-HLA antibodies.

PMID- 22407194
TI  - A chromo- and fluorogenic sensor for probing the cancer biomarker
      lysophosphatidic acid.
AB  - A novel chromo- and fluorogenic sensor, 4-(4-dimethylaminostyryl)-1
      hexadecylpyridinium (DSHP) for lysophosphatidic acid (LPA) was successfully
      developed by incorporating a long alkyl chain into the cyanine molecule. DSHP
      shows excellent selectivity and high sensitivity towards LPA with a detection
      limit of about 7.09 * 10(-7) M based on electrostatic and hydrophobic
      interactions between the sensor and LPA. Upon addition of LPA ranging from 0 to
      7.5 * 10(-4) M, DSHP displays an 'on-off-on' fluorescence response and obvious
      colour change. Good linear relationships between the fluorescence intensity and
      LPA concentrations were achieved in the fluorescence quenching ranges of 0-28 MUM
      and 34-52 MUM, which could be attributed to the combined effects of the
      photoinduced electron transfer and LPA-induced aggregation of the sensor
      molecules.

PMID- 22407195
TI  - Extremely high urine arsenic level after remote seafood ingestion.
AB  - Urine testing for heavy metal concentrations is increasingly performed in the
      outpatient setting as a part of laboratory evaluation for neuropathy. Abnormal
      urine arsenic levels due to dietary intake of organic arsenic can lead to
      unnecessary chelation therapy. A 54-year-old man underwent a 24-hour urine
      collection for heavy metal concentrations in evaluation of paresthesia of the
      right foot. The total arsenic level was 8880 MUg/d with concentrations of 4749
      MUg/L and 3769 MUg/g creatinine. He was urgently referred to the toxicology
      clinic for consideration of chelation therapy. History revealed consumption of 2
      lobster tails 5 days before the testing. Speciation was then performed on the
      original urine specimen and revealed an organic arsenic concentration of 4332
      MUg/L. No inorganic or methylated arsenic was detected. Repeat testing after
      abstaining from seafood demonstrated a total arsenic level of 50 MUg/d with
      concentrations of 30 MUg/L and 21 MUg/g creatinine. Our patient demonstrates the
      highest level of arsenobetaine reported in the literature, and this level is
      higher than expected for a person who had not consumed seafood for 5 days before
      testing. The high levels may be due to consumption of food that he did not
      recognize as containing arsenobetaine or that his clearance of arsenobetaine from
      the ingested lobster is slower than published ranges. This case demonstrates the
      importance of speciation when measuring urine arsenic levels to avoid unnecessary
      chelation therapy. 

PMID- 22407196
TI  - Magnesium sulfate versus ipratropium bromide in chronic obstructive pulmonary
      disease exacerbation: a randomized trial.
AB  - Treatment with short-acting beta2-agonists for exacerbations of chronic
      obstructive pulmonary disease (COPD) results in clinical improvement. It has not
      been established whether combining short-acting beta2-agonists to other
      bronchodilators is more effective than beta2-agonists alone. We conducted a study
      in patients presenting to the emergency department with exacerbation of COPD.
      They were randomized to receive nebulized ipratropium bromide (IB group; n = 62)
      or combined nebulized and intravenous bolus of magnesium sulfate (MgSO4 group; n
      = 62). All nebulized drugs were administered at 30-minute intervals for 2 hours.
      Primary outcome included hospital admission, endotracheal intubation, and
      hospital death rates. Secondary outcome measures were improvement in peak
      expiratory flow, dyspnea score, and arterial blood gas changes within the first 3
      hours. There were no significant differences in primary outcome between MgSO4 and
      IB groups. Patients given IB average 32 L greater improvement in peak expiratory
      flow rate compared with magnesium sulfate (95% confidence interval, 19-43 L) at
      180 minutes. Simultaneously, there was a significant reduction in PaCO2 compared
      with baseline values in IB group but not in MgSO4 group. There was a
      statistically nonsignificant trend toward a decrease in dyspnea score in both
      groups although adverse events were similar. Although the improvement in peak
      expiratory flow rate and arterial blood gas favored nebulized IB over magnesium
      sulfate, there was a nonsignificant difference between both drugs with regard to
      hospital admission, intubation, and hospital death rates in patients with COPD
      treated in the emergency department for acute exacerbation. 

PMID- 22407197
TI  - IV Penicillin G is as effective as IV cefuroxime in treating community-acquired
      pneumonia in children.
AB  - Overuse of broad-spectrum antimicrobials has resulted in bacterial resistance and
      increasing use of relatively expensive antibiotics for community-acquired
      pneumonia (CAP). We hypothesized that CAP requiring parenteral medication is
      still curable with narrow-spectrum and inexpensive penicillin G. A prospective,
      randomized study was performed on 58 children aged 3 months to 15 years with CAP.
      Children were randomly assigned to receive low-dose penicillin G, high penicillin
      G, or cefuroxime intravenously for 4-7 days. The course of illness was monitored
      clinically and with predetermined laboratory and radiological indices for 30
      days. The children recovered at the same rate with no significant differences in
      time to defervescence or duration of hospitalization. Observed differences in
      leukocyte counts and C-reactive protein at discharge were of questionable
      clinical significance. Penicillin G is as effective and safe as cefuroxime for
      CAP in otherwise healthy children, even in moderate doses. 

PMID- 22407198
TI  - Toxicity from repeated doses of acetaminophen in children: assessment of
      causality and dose in reported cases.
AB  - Liver injury has been reported in children treated with repeated doses of
      acetaminophen. The objective of this study was to identify and validate reports
      of liver injury or death in children younger than 6 years who were administered
      repeated therapeutic doses of acetaminophen. We reviewed US Poison Center data,
      peer-reviewed literature, US Food and Drug Administration Adverse Event Reports,
      and US Manufacturer Safety Reports describing adverse effects after acetaminophen
      administration. Reports that described hepatic abnormalities (description of
      liver injury or abnormal laboratory testing) or death after acetaminophen
      administration to children younger than 6 years were included. The identified
      reports were double abstracted and then reviewed by an expert panel to determine
      if the hepatic injury was related to acetaminophen and whether the dose of
      acetaminophen was therapeutic (<=75 mg/kg) or supratherapeutic. Our search
      yielded 2531 reports of adverse events associated with acetaminophen use. From
      these cases, we identified 76 cases of hepatic injury and 26 deaths associated
      with repeated acetaminophen administration. There were 6 cases of hepatic
      abnormalities and no deaths associated with what our panel determined to be
      therapeutic doses. A large proportion of cases could not be fully evaluated due
      to incomplete case reporting. Although we identified numerous examples of liver
      injury and death after repeated doses of acetaminophen, all the deaths and all
      but 6 cases of hepatic abnormalities involved doses more than 75 mg/kg per day.
      This study suggests that the doses of less than 75 mg/kg per day of acetaminophen
      are safe for children younger than 6 years. 

PMID- 22407199
TI  - The role of severity of obstructive sleep apnea measured by apnea-hypopnea index
      in predicting compliance with pressure therapy, a meta-analysis.
AB  - Obstructive sleep apnea (OSA) is associated with diabetes, hypertension, stroke,
      coronary artery disease, and premature death. Positive airway pressure (PAP) is
      the mainstay of therapy. Despite its effective treatment with PAP therapy,
      noncompliance remains high. Many factors determine compliance. The role of
      severity of OSA measured by the apnea-hypopnea index (AHI) remains controversial.
      Meta-analysis of studies examining this role of AHI was performed. A systematic
      review of the medical literature was conducted using PubMed and Cochrane library
      by utilizing different combinations of key words: sleep apnea, AHI, compliance,
      and nonadherence. Inclusion criteria were English articles; Studies with adult
      population; with 2 groups of patients (compliant and noncompliant); Studies
      utilizing objective definition of compliance (PAP usage of >4 hours per night for
      70% of days or usage >5 d/wk and for >4 hours per night). Studies were analyzed
      by standard methods of meta-analysis. The studies were heterogeneous for AHI;
      therefore, the random effect model was used. Six hundred forty-one manuscripts
      were found. Of these, 230 were found to be appropriate for full text evaluation.
      Thirty-one met inclusion criteria. Twelve of these studies used objective
      criteria for PAP compliance and were hence included in meta-analysis. All the
      subjects had OSA determined by polysomnography, for whom PAP was employed.
      Compliance to PAP therapy was evaluated after a period of time ranging from 4
      weeks to 8 years. There were 1438 subjects included in the meta-analysis; 886
      subjects were PAP compliant, whereas 552 subjects were noncompliant. A greater
      AHI was found in PAP compliant patients. The mean difference between compliant
      and noncompliant groups was 5.9 (95% confidence interval: 0.19-11.67, P < 0.05).
      Patients with mild OSA are less likely to be compliant with PAP therapy. These
      patients should receive aggressive management particularly at the start of
      therapy with close follow-up to increase compliance. 

PMID- 22407200
TI  - North Star Summit: the vision for the future.

PMID- 22407201
TI  - Prologue.

PMID- 22407202
TI  - North Star Invitational Summit: state of the science on nurse executive practice
      creating the vision for the future.

PMID- 22407203
TI  - Service and scholarship: an evolutionary examination of nursing administration.
AB  - This article characterizes the evolution and impact of nursing administration
      scholarship on administrative practice over the past several decades. Through a
      critical examination of the literature, this article (1) uncovers how the
      evolution of nursing scholarship has influenced administrative practice over
      time; (2) articulates a current conceptualization of nursing administration by
      describing the responsibilities, necessary expertise, and challenges that
      characterize the work of nurse administrators (NAs); and (3) reflects on these
      findings to raise questions about how to further cultivate synergistic
      relationships between nursing science and administrative practice in the future.
      This synthesis of the literature revealed that partnerships between service and
      scholarship have been at the heart of advancing administrative education and
      practice for many years. While the major responsibilities of NAs have not changed
      significantly over the past several decades, the concepts and measures NAs employ
      have evolved. Nursing scholarship has refined terminology and developed measures
      that have changed the ways in which NAs approach their responsibilities and
      conceptualize their practice. These developments have furthered nurse scholars'
      efforts to conduct research pertinent to administrative practice. Still, there
      are many issues left to be explored, and the opportunities for advancing the
      science in this domain of nursing practice are vast.

PMID- 22407204
TI  - Advancing high value transitional care: the central role of nursing and its
      leadership.
AB  - Addressing the health care needs of older adults coping with multiple conditions
      and their family caregivers in a person- and family-centered, safe, effective,
      efficient, equitable, and timely manner will be a major issue confronting
      America's health care system for the foreseeable future. This article describes
      the efforts of a multidisciplinary team to create a path from system
      fragmentation to integration for this vulnerable population through the design,
      testing, and translation of the Transitional Care Model (TCM). The TCM is a nurse
      led, team-based care delivery system innovation that is designed to increase
      alignment of the care system with the preferences, needs, and values of high-risk
      individuals and their family caregivers and achieve higher-quality outcomes while
      reducing health care costs. A rigorous body of evidence reinforces a tremendous
      opportunity to address the urgent need for higher-value health care, through
      widespread implementation of the TCM for chronically ill older adults.
      Capitalizing on this opportunity will require the investment, commitment, and
      support of nursing and its leadership.

PMID- 22407205
TI  - Achieving a high-reliability organization through implementation of the ARCC
      model for systemwide sustainability of evidence-based practice.
AB  - High-reliability health care organizations are those that provide care that is
      safe and one that minimizes errors while achieving exceptional performance in
      quality and safety. This article presents major concepts and characteristics of a
      patient safety culture and a high-reliability health care organization and
      explains how building a culture of evidence-based practice can assist
      organizations in achieving high reliability. The ARCC (Advancing Research and
      Clinical practice through close Collaboration) model for systemwide
      implementation and sustainability of evidence-based practice is highlighted as a
      key strategy in achieving high reliability in health care organizations.

PMID- 22407206
TI  - The importance of knowledge-based technology.
AB  - Nurse executives are responsible for a workforce that can provide safer and more
      efficient care in a complex sociotechnical environment. National quality
      priorities rely on technologies to provide data collection, share information,
      and leverage analytic capabilities to interpret findings and inform approaches to
      care that will achieve better outcomes. As a key steward for quality, the nurse
      executive exercises leadership to provide the infrastructure to build and manage
      nursing knowledge and instill accountability for following evidence-based
      practices. These actions contribute to a learning health system where new
      knowledge is captured as a by-product of care delivery enabled by knowledge-based
      electronic systems. The learning health system also relies on rigorous scientific
      evidence embedded into practice at the point of care. The nurse executive
      optimizes use of knowledge-based technologies, integrated throughout the
      organization, that have the capacity to help transform health care.

PMID- 22407207
TI  - The transformative power of personal and organizational leadership.
AB  - Transformational leadership has both personal and professional domains. Key
      concepts and research related to transformational leadership are explored, as
      well as a framework for personal and professional leadership, in relation to
      leadership of self, leadership in relation to others, and leadership in relation
      to systems. A review of the issues and trends facing nurse executives results in
      identification of the research gaps in personal and professional leadership as it
      impacts nursing practice, and suggestions about potential research agenda items
      for executive nurse leadership in practice are discussed.

PMID- 22407208
TI  - The organizational transformative power of nurse residency programs.
AB  - Residency programs for newly licensed registered nurses (NLRNs) have been
      strongly advocated by the Institute of Medicine, American Organization of Nurse
      Executives, and other professional organizations. Their cost-effectiveness as
      well as their impact on NLRN retention, job and practice satisfaction, improved
      performance, and reduction in environmental reality shock has been demonstrated.
      This qualitative study sought answers to the question: what people, components,
      processes and activities of Nurse Residency Programs (NRPs), and the work
      environment are instrumental in the transition and integration of NLRNs into the
      professional practice role and into professional communities? In the course of
      interviewing 907 nurses-NLRNs, experienced nurses, managers, and educators
      practicing on clinical units with confirmed "very healthy work environments" in
      20 Magnet hospitals, it became evident that not only did NRPs positively impact
      the professional socialization of NLRNs, they led to transformative changes in
      the organization and in the practice of other health care professionals. The
      organizational transformative changes described by the interviewees are presented
      for each of the 7 major challenges identified by NLRNs-delegation,
      prioritization, managing patient care delivery, autonomous decision-making,
      collaboration with other disciplines, constructive conflict resolution, and
      utilizing feedback to restore self-confidence. If it can be demonstrated that
      these transformative changes stimulated by NRPs also lead to improved patient
      outcomes, NRPs may be the most significant organization transformation instituted
      by nurse leaders in recent years.

PMID- 22407209
TI  - Preparing tomorrow's service leaders: an educational challenge.
AB  - Preparing the leaders of any profession is a challenge, and even more so for
      nursing based on the diversity of settings, the complexity of health care, and
      the lack of advanced education for many of the leadership roles in nursing. As
      education costs continue to rise and many eager college students are unable to be
      accepted into schools of nursing, the number of prospects for leadership is
      growing slowly.

PMID- 22407210
TI  - Epilogue: 2011 North Star Invitational Summit.

PMID- 22407211
TI  - Spectroscopically characterized cadmium sulfide quantum dots lengthening the lag
      phase of Escherichia coli growth.
AB  - The present study reports the effect of cadmium sulfide (CdS) quantum dots on the
      life cycle of Escherichia coli. CdS quantum dots were synthesized by pH sensitive
      organochemical route using cadmium chloride and sodium sulfide as precursors and
      mercaptopropionic acid (MPA) as capping agent. It is observed that varying
      concentration of MPA leads to the production of different sized quantum dots with
      inverse proportionality and increment in the fluorescence quantum yield. The
      investigation also shows that CdS quantum dots have no antibacterial activity
      except it delays the log phase growth of bacteria in terms of size of the
      particles. The largest synthesized particles significantly elongate the lag phase
      growth.

PMID- 22407212
TI  - Interaction between La(III) and proteins on the plasma membrane of horseradish.
AB  - Lanthanum (La) is an important rare earth element in the ecological environment
      of plant. The proteins on the plasma membrane control the transport of molecules
      into and out of cell. It is very important to investigate the effect of La(III)
      on the proteins on the plasma membrane in the plant cell. In the present work,
      the interaction between La(III) and proteins on the plasma membrane of
      horseradish was investigated using optimization of the fluorescence microscopy
      and fluorescence spectroscopy. It is found that the fluorescence of the complex
      system of protoplasts and 1-aniline Kenai-8-sulfonic acid in horseradish treated
      with the low concentration of La(III) is increased compared with that of the
      control horseradish. The opposite effect is observed in horseradish treated with
      the high concentration of La(III). These results indicated that the low
      concentration of La(III) can interact with the proteins on the plasma membrane of
      horseradish, causing the improvement in the structure of proteins on the plasma
      membrane. The high concentration of La(III) can also interact with the proteins
      on the plasma membrane of horseradish, leading to the destruction of the
      structure of proteins on the plasma membrane. We demonstrate that the proteins on
      the plasma membrane are the targets of La(III) action on plant cell.

PMID- 22407213
TI  - Palladium-catalysed aminosulfonylation of aryl-, alkenyl- and heteroaryl halides:
      scope of the three-component synthesis of N-aminosulfonamides.
AB  - By using DABCO.(SO(2))(2), DABSO, as a solid bench-stable SO(2)-equivalent, the
      palladium-catalysed aminosulfonylation of aryl-, alkenyl- and heteroaryl halides
      has been achieved. N,N-Dialkylhydrazines are employed as the N-nucleophiles and
      provide N-aminosulfonamides as the products in good to excellent yields. The
      reactions are operationally simple to perform, requiring only a slight excess of
      SO(2) (1.2-2.2 equiv.), and tolerate a variety of substituents on the halide
      coupling partner. Variation of the hydrazine component is also demonstrated. The
      use of N,N-dibenzylhydrazine as the N-nucleophile delivers N-aminosulfonamide
      products that can be converted into the corresponding primary sulfonamides using
      a high-yielding, telescoped, deprotection sequence. The ability to employ
      hydrazine.SO(2) complexes as both the N-nucleophile and SO(2) source is also
      illustrated.

PMID- 22407214
TI  - [18F]-Fluorodeoxyglucose positron emission tomography in children with
      neurofibromatosis type 1 and plexiform neurofibromas: correlation with malignant
      transformation.
AB  - The objective of this study was to investigate the predictive value of [18F]
      fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting malignant
      transformation of plexiform neurofibromas in children with neurofibromatosis type
      1 (NF1). An electronic search of the medical records was performed to determine
      patients with NF1 who had undergone FDG-PET for plexiform neurofibroma between
      2000 and 2011. All clinical, radiologic, pathology information and operative
      reports were reviewed. Relationship between histologic diagnosis, radiologic
      features and FDG-PET maximum standardized uptake value (SUV(max)) was evaluated.
      This study was approved by the Institutional Review Board of our institution.
      1,450 individual patients were evaluated in our Multidisciplinary
      Neurofibromatosis Program, of whom 35 patients underwent FDG-PET for suspected
      MPNST based on change or progression of clinical symptoms, or MRI findings
      suggesting increased tumor size. Twenty patients had concurrent pathologic
      specimens from biopsy/excision of 27 distinct lesions (mean age 14.9 years).
      Pathologic interpretation of these specimens revealed plexiform and atypical
      plexiform neurofibromas (n = 8 each), low grade MPNST (n = 2), intermediate grade
      MPNST (n = 4), high grade MPNST (n = 2), GIST (n = 1) and non-ossifying fibroma
      (n = 1). SUV(max) of plexiform neurofibromas (including typical and atypical) was
      significantly different from MPNST (2.49 (SD = 1.50) vs. 7.63 (SD = 2.96), p <
      0.001). A cutoff SUV(max) value of 4.0 had high sensitivity and specificity of
      1.0 and 0.94 to distinguish between PN and MPNST. FDG-PET can be helpful in
      predicting malignant transformation in children with plexiform neurofibromas and
      determining the need for biopsy and/or surgical resection.

PMID- 22407218
TI  - A suitable and efficient procedure for the removal of decontaminating antibiotics
      from tissue allografts.
AB  - The presence of residual antibiotics in tissue allografts after decontamination
      with antibiotic cocktails may result in widely documented adverse effects in
      predisposed subjects. Moreover, antibiotic residues may mask contaminating
      microorganisms, resulting in falsely negative sterility tests, with potential
      risk of post-surgical infections. The objective of the present study was to
      define a rinsing procedure capable of eliminating antibiotic residues from
      cardiovascular, bone and skin tissues after decontamination with BASE.128.
      Different washing patterns, employing BASE medium, were applied. The presence of
      antibiotic residues in tissue homogenates was assessed by agar diffusion test at
      different stages of tissue processing. To test whether antibiotic residues can
      result in falsely negative microbiological analysis, we induced a superficial
      tissue contamination with known inoculum concentration. By employing four
      different porcine tissues, we here report direct evidence that the presence of
      even limited amounts of antibiotics in decontaminated tissues interferes with
      sterility testing. This has implications in terms of increased risk of infections
      in allograft recipients. To minimize this risk, we developed a procedure for
      extensive removal of antibiotics from allografts, allowing for subsequent
      detection of microbial contaminations that may occur during transportation,
      storage or processing prior to allograft transplantation. Our study emphasizes
      the importance of validating all processes and analytical methods in tissue
      banking, in order to warrant tissue safety. This will minimize the risks of post
      surgical infections as well as antibiotic-induced anaphylaxis in predisposed
      patients.

PMID- 22407215
TI  - Microdomain heterogeneity in 3D affects the mechanics of neonatal cardiac myocyte
      contraction.
AB  - Cardiac muscle cells are known to adapt to their physical surroundings,
      optimizing intracellular organization and contractile function for a given
      culture environment. A previously developed in vitro model system has shown that
      the inclusion of discrete microscale domains (or microrods) in three dimensions
      (3D) can alter long-term growth responses of neonatal ventricular myocytes. The
      aim of this work was to understand how cellular contact with such a domain
      affects various mechanical changes involved in cardiac muscle cell remodeling.
      Myocytes were maintained in 3D gels over 5 days in the presence or absence of 100
      MUm-long microrods, and the effect of this local heterogeneity on cell behavior
      was analyzed via several imaging techniques. Microrod abutment resulted in
      approximately twofold increases in the maximum displacement of spontaneously
      beating myocytes, as based on confocal microscopy scans of the gel xy-plane or
      the myocyte long axis. In addition, microrods caused significant increases in the
      proportion of aligned myofibrils (<=20 degrees  deviation from long axis) in
      fixed myocytes. Microrod-related differences in axial contraction could be
      abrogated by long-term interruption of certain signals of the RhoA-/Rho
      associated kinase (ROCK) or protein kinase C (PKC) pathway. Furthermore, microrod
      induced increases in myocyte size and protein content were prevented by ROCK
      inhibition. In all, the data suggest that microdomain heterogeneity in 3D appears
      to promote the development of axially aligned contractile machinery in muscle
      cells, an observation that may have relevance to a number of cardiac tissue
      engineering interventions.

PMID- 22407219
TI  - Evaluation of the mean energy deposit during the impact of charged particles on
      liquid water.
AB  - The DNA strand break yield due to the impact of ionizing particles on living
      beings is closely related to the number of inelastic events per unit absorbed
      dose produced by these particles. The higher this number, the higher the
      probability of causing DNA strand breaks per unit absorbed dose. In a previous
      work, it was found that the total number of events produced by primary particles
      and the secondary electrons is almost independent of the type and energy of the
      incident particle (or LET). This finding could be supported by a quasi-constant
      mean energy deposit by inelastic event (epsilon). In this work, epsilon was
      defined and determined for electrons and the non-negative charge states of
      hydrogen (H0,+) and helium (He0,+,2+) species impacting on liquid water.
      Ionization, excitation and charge transfer (up to two-electron transfers)
      processes have been included in present calculations. We found that, for liquid
      water, epsilon is within 13.7 +/- 4.1 eV, 14.2 +/- 1.7 eV and 13.8 +/- 1.4 eV for
      electrons, hydrogen and helium species, respectively, with impact energies
      changing over three orders of magnitude. Unlike the mean excitation energy, the
      mean energy deposit per inelastic event depends not only on the target molecule
      but also on the projectile features. However, this dependence is relatively weak.
      This fact supports the quasi-independent number of inelastic events per unit
      absorbed dose found previously when charged particles impact on matter.

PMID- 22407220
TI  - In situ electrochemical assay of cell surface sialic acids featuring highly
      efficient chemoselective recognition and a dual-functionalized nanohorn probe.
AB  - A novel electrochemical strategy was developed for in situ detection and dynamic
      monitoring of cell surface sialic acids using a highly efficient chemoselective
      labeling technique and a dual-functionalized nanohorn probe for signal
      amplification.

PMID- 22407221
TI  - Learning from storytelling.

PMID- 22407222
TI  - Gender differences in the social functioning of adolescents with inflammatory
      bowel disease.
AB  - Inflammatory bowel disease (IBD) has been associated with social difficulties.
      Boys with IBD may have increased risk for social problems due to delayed growth
      and puberty, but gender differences in social functioning have not been
      investigated. This study examined gender differences in multiple areas of social
      functioning for adolescents with IBD compared to healthy adolescents.
      Participants were 92 adolescents 11-17 years (50 with IBD, 42 healthy) and
      parents who completed questionnaires assessing social functioning. IBD was
      associated with poorer social functioning in the areas of social competence and
      social problems. Boys with IBD had worse social competence, with no gender
      differences for social problems. Gender predicted the use of social contact as a
      coping strategy, but no significant group differences were found for other areas
      of social functioning. Adolescents with IBD experience significant social
      difficulties in some areas, and boys are at risk for poor social competence.
      However, previously reported social difficulties may not extend to all areas of
      social functioning.

PMID- 22407223
TI  - Magnetic resonance imaging in E200K and V210I mutations of the prion protein
      gene.
AB  - Magnetic resonance imaging (MRI), with diffusion-weighted imaging (DWI) and fluid
      attenuated inversion recovery (FLAIR), is a useful diagnostic investigation for
      Creutzfeldt-Jakob disease (CJD). Amendment of the diagnostic criteria for
      sporadic CJD (sCJD) to include defined MRI alterations has just recently been
      proposed. We analyzed MRI scans with FLAIR and/or DWI available of 29 patients
      with the E200K or the V210I mutation, and a control group of 29 sCJD patients to
      compare the MRI lesion profile and evaluate the applicability of new MRI criteria
      to genetic CJD patients. FLAIR images of all 29 patients and controls and DWI
      images of 15 genetic CJD and 13 sCJD were rated by 2 neuroradiologists blinded to
      diagnosis and genetic testing. In genetic CJD (gCJD) patients, hyperintensities
      on FLAIR could be found in the putamen in 55% and the caudate nucleus in 66% and
      on DWI in 33% and 60%, respectively. Lesion profile and frequency of
      hyperintensities did not differ significantly from the findings in sCJD. New
      diagnostic MRI criteria yield similar sensitivity for gCJD and sCJD, being 79%
      and 72%, respectively. MRI provides useful information in E200K and V210I gCJD
      patients. The alterations strongly resembled those seen in sCJD, once again
      demonstrating the similarity of the clinical syndrome in patients with these
      particular mutations.

PMID- 22407224
TI  - Theory of mind and recognition of facial emotion in dementia: challenge to
      current concepts.
AB  - Current literature suggests that theory of mind (ToM) and recognition of facial
      emotion are impaired in behavioral variant frontotemporal dementia (bvFTD). In
      contrast, studies suggest that ToM is spared in Alzheimer disease (AD). However,
      there is controversy whether recognition of emotion in faces is impaired in AD.
      This study challenges the concepts that ToM is preserved in AD and that
      recognition of facial emotion is impaired in bvFTD. ToM, recognition of facial
      emotion, and identification of emotions associated with video vignettes were
      studied in bvFTD, AD, and normal controls. ToM was assessed using false-belief
      and visual perspective-taking tasks. Identification of facial emotion was tested
      using Ekman and Friesen's pictures of facial affect. After adjusting for relevant
      covariates, there were significant ToM deficits in bvFTD and AD compared with
      controls, whereas neither group was impaired in the identification of emotions
      associated with video vignettes. There was borderline impairment in recognizing
      angry faces in bvFTD. Patients with AD showed significant deficits on false
      belief and visual perspective taking, and bvFTD patients were impaired on second
      order false belief. We report novel findings challenging the concepts that ToM is
      spared in AD and that recognition of facial emotion is impaired in bvFTD.

PMID- 22407225
TI  - Relating memory to functional performance in normal aging to dementia using
      hierarchical Bayesian cognitive processing models.
AB  - Determining how cognition affects functional abilities is important in Alzheimer
      disease and related disorders. A total of 280 patients (normal or Alzheimer
      disease and related disorders) received a total of 1514 assessments using the
      functional assessment staging test (FAST) procedure and the MCI Screen. A
      hierarchical Bayesian cognitive processing model was created by embedding a
      signal detection theory model of the MCI Screen-delayed recognition memory task
      into a hierarchical Bayesian framework. The signal detection theory model used
      latent parameters of discriminability (memory process) and response bias
      (executive function) to predict, simultaneously, recognition memory performance
      for each patient and each FAST severity group. The observed recognition memory
      data did not distinguish the 6 FAST severity stages, but the latent parameters
      completely separated them. The latent parameters were also used successfully to
      transform the ordinal FAST measure into a continuous measure reflecting the
      underlying continuum of functional severity. Hierarchical Bayesian cognitive
      processing models applied to recognition memory data from clinical practice
      settings accurately translated a latent measure of cognition into a continuous
      measure of functional severity for both individuals and FAST groups. Such a
      translation links 2 levels of brain information processing and may enable more
      accurate correlations with other levels, such as those characterized by
      biomarkers.

PMID- 22407226
TI  - Distribution of Chlamydia trachomatis serotypes in clinical urogenital samples
      from north-eastern Croatia.
AB  - The purpose of this study was to determine prevalence of Chlamydia trachomatis
      (Ct) urogenital infection and its serotype distribution from clinical samples in
      north-eastern Croatia. During a 3-year period, 2,379 urogenital samples were
      analyzed by real-time polymerase chain reaction (A group), while 4,846 genital
      swabs were analyzed by direct fluorescent antibody test (B group). 132 Ct
      positive specimens were genotyped by omp1 gene sequencing. The prevalence rate of
      Ct was 3.2 % in A and 1 % in B group. The most prevalent chlamydial genotype was
      E (44 %), followed by F (33 %), K (11.5 %), G (8 %), J/UW (5.3 %), D-IC (4.4 %),
      D-B120 (1.8 %), and B/IU, J/IU, Ia/IU (0.9 % each) serotypes. Single-nucleotide
      polymorphisms (SNPs) of omp1 gene were detected in E, K, and G serotypes. Some of
      these SNPs (C/T at position 272 and G/A at position 813 in E strain; C/T at
      position 884 in D strain) might represent novel omp1 variants.

PMID- 22407227
TI  - Comparison of the effects of cholecalciferol and calcitriol on calcium metabolism
      and bone turnover in Chinese postmenopausal women with vitamin D insufficiency.
AB  - AIM: To compare the effects of cholecalciferol (800 IU/d) and calcitriol (0.25
      MUg/d) on calcium metabolism and bone turnover in Chinese postmenopausal women
      with vitamin D insufficiency. METHODS: One hundred Chinese postmenopausal women
      aged 63.8+/-7.0 years and with serum 25-hydroxyvitamin D [25(OH)D] concentration
      <30 ng/mL were recruited. The subjects were divided into 2 groups based on the
      age and serum 25(OH)D concentration: 50 subjects (group A) received
      cholecalciferol (800 IU/d), and 50 subjects (group B) received calcitriol (0.25
      MUg/d) for 3 months. In addition, all the subjects received Caltrate D (calcium
      plus 125 IU cholecalciferol) daily in the form of one pill. The markers of
      calcium metabolism and bone turnover, including the serum levels of calcium,
      phosphorus, alkaline phosphatase, intact parathyroid hormone, 25(OH)D and beta
      CrossLaps of type I collagen containing cross-linked C-telopeptide (beta-CTX),
      were measured before and after the intervention. RESULTS: After the 3-month
      intervention, the serum 25(OH)D concentration in group A was significantly
      increased from 16.01 +/- 5.0 to 20.02 +/- 4.5 ng/mL, while that in group B had no
      significant change. The serum calcium levels in both the groups were
      significantly increased (group A: from 2.36 +/- 0.1 to 2.45 +/- 0.1 mmol/L; group
      B: from 2.36 +/- 0.1 to 2.44 +/- 0.1 mmol/L). The levels of serum intact
      parathyroid hormone in both the groups were significantly decreased (group A:
      from 48.56 +/- 12.8 to 39.59 +/- 12.6 pg/mL; group B: from 53.67 +/- 20.0 to
      40.32 +/- 15.4 pg/mL). The serum levels of beta-CTX in both the groups were also
      significantly decreased (group A: from 373.93 +/- 135.3 to 325.04 +/- 149.0 ng/L;
      group B: from 431.00 +/- 137.1 to 371.74 +/- 185.0 ng/L). CONCLUSION: We
      concluded that both cholecalciferol (800 IU/d) and calcitriol (0.25 MUg/d) plus
      Caltrate D modifies the serum calcium and bone turnover markers in Chinese
      postmenopausal women with vitamin D insufficiency. In addition, cholecalciferol
      (800 IU/d) significantly increased the serum 25(OH)D concentration.

PMID- 22407228
TI  - Perifosine induces protective autophagy and upregulation of ATG5 in human chronic
      myelogenous leukemia cells in vitro.
AB  - AIM: The efficacy of the Akt inhibitor perifosine against chronic myeloid
      leukemia (CML) cells and its mechanisms of action are unknown. In this study, the
      cytotoxic effects of perifosine on CML and acute myeloid leukemia (AML) cell
      lines were compared to elucidate the mechanisms underlying the differences.
      METHODS: Human AML cell lines Kasumi-1 and HL-60, and the CML cell line K562 were
      used. Cell viability was quantitated using MTT assay. Apoptosis was determined
      using Annexin V-FITC/propidium iodide and Hoechst staining, which were followed
      by flow cytometry and fluorescence microscopy analysis, respectively. Caspase
      pathway activation and the expression of autophagy-related genes were examined
      using Western blot. Autophagy was studied using electron microscopy, the acridine
      orange staining method, and GFP-LC3 was examined with fluorescence microscopy.
      RESULTS: In contrast to AML cell lines, the CML cell lines K562 and K562/G (an
      imatinib-insensitive CML cell line) were resistant to perifosine (2.5-20 MUmol/L)
      in respect to inhibiting cell growth and inducing apoptosis. Perifosine (2.5, 5,
      and 10 MUmol/L) inhibited Akt and its phosphorylation in AML cells, but not in
      CML cells. Treatment with perifosine (20 MUmol/L) resulted in autophagy in CML
      cells as shown by the increased formation of acidic vesicular organelles and the
      accumulation of LC3-II. Treatment of CML cells with perifosine (5, 10, and 20
      MUmol/L) dose-dependently upregulated AGT5, but not Beclin 1 at the protein
      level. Furthermore, inhibition of autophagy by chloroquine (40 nmol/L)
      significantly suppressed the cell growth and induced apoptosis in CML cells
      treated with perifosine (20 MUmol/L). CONCLUSION: Our results show that CML cell
      lines were resistant to the Akt inhibitor perifosine in vitro, which is due to
      perifosine-induced protective autophagy and upregulation of ATG5.

PMID- 22407229
TI  - Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium
      channels in cultured rat hippocampal neurons.
AB  - AIM: To investigate the effect of ginsenoside Rb1 on voltage-gated calcium
      currents in cultured rat hippocampal neurons and the modulatory mechanism.
      METHODS: Cultured hippocampal neurons were prepared from Sprague Dawley rat
      embryos. Whole-cell configuration of the patch-clamp technique was used to record
      the voltage-gated calcium currents (VGCCs) from the hippocampal neurons,and the
      effect of Rb1 was examined. RESULTS: Rb1 (2-100 MUmol/L) inhibited VGCCs in a
      concentration-dependent manner, and the current was mostly recovered upon wash
      out. The specific L-type Ca(2+) channel inhibitor nifedipine (10 MUmol/L)
      occluded Rb1-induced inhibition on VGCCs. Neither the selective N-type Ca(2+)
      channel blocker omega-conotoxin-GVIA (1 MUmol/L), nor the selective P/Q-type
      Ca(2+) channel blocker omega-agatoxin IVA (30 nmol/L) diminished Rb1-sensitive
      VGCCs. Rb1 induced a leftward shift of the steady-state inactivation curve of
      I(Ca) to a negative potential without affecting its activation kinetics or
      reversal potential in the I-V curve. The inhibitory effect of Rb1 was neither
      abolished by the adenylyl cyclase activator forskolin (10 MUmol/L), nor by the
      PKA inhibitor H-89 (10 MUmol/L). CONCLUSION: Ginsenoside Rb1 selectively inhibits
      the activity of L-type voltage-gated calcium channels, without affecting the N
      type or P/Q-type Ca(2+) channels in hippocampal neurons. cAMP-PKA signaling
      pathway is not involved in this effect.

PMID- 22407230
TI  - Lentivirus-mediated RNA silencing of c-Met markedly suppresses peritoneal
      dissemination of gastric cancer in vitro and in vivo.
AB  - AIM: To investigate the expression of c-Met in peritoneal free cancer cells
      isolated from human gastric cancer ascites, and its relationship to peritoneal
      dissemination of gastric cancer. METHODS: Peritoneal free cancer cells (PFCCs)
      were isolated from ascites specimens of gastric cancer patients. c-Met expression
      in PFCCs was detected with immunocytochemistry. In human gastric cancer cell line
      SGC7901, c-Met expression was detected using RT-PCR and Western blot, and was
      suppressed with lentivirus-mediated RNAi. The proliferation of SGC7901 cells was
      measured using MTT assay, and the invasion ability was detected with invasion
      assay. The adhesion of SGC7901 cells to peritoneum was observed in human
      peritoneal mesothelial cells (HPMCs) monolayer in vitro and in mice in vivo.
      RESULTS: PFCCs were isolated from ascites of 6 out of 10 gastric cancer patients.
      c-Met expression in PFCCs was detected in 5 of the 6 gastric cancer patients. In
      SGC7901 cells, Lentivirus-mediated RNAi significantly reduced both c-Met mRNA and
      protein expression, which resulted in suppressing the cell proliferation,
      invasion and adhesion to peritoneum. The expression of alpha3beta1 integrin and E
      cadherin was significantly inhibited in SGC7901 cells transfected with Lenti
      miRNAc-Met. In the peritoneal dissemination model of gastric cancer,
      intraperitoneal injection of Lenti-miRNAc-Met markedly suppressed the tumor
      Progression of SGC7901 cells. CONCLUSION: c-Met is expressed in PFCCs from the
      ascites of gastric cancer patients. Down-regulation of c-Met expression markedly
      suppresses the multistep process of peritoneal dissemination, thus may be a
      potential target for the treatment of gastric cancer.

PMID- 22407232
TI  - Is cell-free fetal DNA from maternal blood finally ready for prime time?

PMID- 22407231
TI  - A toxicological and dermatological assessment of aryl alkyl alcohol simple acid
      ester derivatives when used as fragrance ingredients.
AB  - The aryl alkyl alcohol simple acid ester derivatives (AAASAE) group of fragrance
      ingredients was critically evaluated for safety following a complete literature
      search of the pertinent data. For high end users, calculated maximum skin
      exposures vary widely from 0.01% to 4.17%. AAASAE exhibit a common route of
      primary metabolism by carboxylesterases resulting in the formation of the simple
      acid and an aryl alkyl alcohol. They have low acute toxicity. No significant
      toxicity was observed in repeat-dose toxicity tests. There was no evidence of
      carcinogenicity of benzyl alcohol when it was administered in the feed; gavage
      studies resulted in pancreatic carcinogenesis due to the corn oil vehicle. The
      AAASAE are not mutagenic in bacterial systems or in vitro in mammalian cells, and
      have little to no in vivo genotoxicity. Reproductive and developmental toxicity
      data show no indication of adverse effects on reproductive function and NOELs for
      maternal and developmental toxicity are far in excess of current exposure levels.
      The AAASAE are generally not irritating or sensitizing at the current levels of
      exposure. The Panel is of the opinion that there are no safety concerns regarding
      the AAASAE at the current levels of use and exposure.

PMID- 22407233
TI  - Sexual function in women following transvaginal mesh procedures for the treatment
      of pelvic organ prolapse.
AB  - INTRODUCTION AND HYPOTHESIS: Synthetic mesh kits recently adopted in pelvic
      reconstructive surgeries have achieved great surgical efficacy, but the effects
      of transvaginal synthetic mesh procedures on women's sexual function are still
      controversial. This study was conducted to demonstrate sexual function in women
      before and after surgery with transvaginal mesh (TVM) repair for pelvic organ
      prolapse (POP). METHODS: A total of 93 sexually active women scheduled for
      correcting POP with synthetic mesh kits were recruited. In addition to
      urogynecological history, pelvic examination by the Pelvic Organ Prolapse
      Quantification system, and urodynamic testing, consenting participants were asked
      to complete the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire
      (PISQ-12) to evaluate sexual function before and after surgery. RESULTS: At the 3
      month urodynamic studies, among the 25 patients with coexistent urodynamic stress
      incontinence (USI) who had undergone a concomitant transobturator suburethral
      tape procedure (TOT), 1 (4 %) had persistent USI; 8 of 68 (11.8 %) patients with
      a negative pessary test developed postoperative USI. Six-month prolapse
      recurrence rates following TVM alone and TVM with concomitant TOT were 9 and 12
      %, respectively. The total PISQ-12 score after surgery showed worse results in
      the TVM alone group but not in the TVM with concomitant TOT group. The individual
      scores of PISQ-12 after surgery demonstrated prolapse-related items improved in
      both TVM groups; sexual function worsened in dyspareunia and behavior domains.
      CONCLUSIONS: Our data revealed that transvaginal synthetic mesh procedures for
      the treatment of POP generated favorable clinical outcomes, but situations might
      worsen in dyspareunia and behavior domains, thereby invoking a negative emotional
      reaction during intercourse after surgery.

PMID- 22407234
TI  - Obstructing urethral calculus in a woman revealed to be the cause of chronic
      pelvic pain.
AB  - Urethral calculi are extremely rarely reported in Caucasian females and are
      usually associated with an anatomical abnormality such as a diverticulum or a
      stricture. Ureteric calculi can move to become lodged in the urethra, although
      this is rare in women because of their short urethral length. We present a case
      of a 55-year-old woman presenting with urinary retention secondary to an
      obstructing upper tract calculus that had moved into the urethra. Four years
      previously, the patient had been diagnosed with chronic pelvic pain following a
      primary posterior vaginal wall repair. Following treatment of the obstructing
      calculus, her symptoms of pelvic pain completely resolved. We report a very
      unusual case that highlights the importance of investigating chronic pelvic pain.
      This patient's symptom of vaginal pain, though highly localized, was caused by
      pathology elsewhere in the pelvis. Alternative diagnoses should be sought for
      such patients and investigation performed to detect any nonvisible hematuria.

PMID- 22407236
TI  - Intramolecular reductive ketone-alkynoate coupling reaction promoted by (eta2
      propene)titanium.
AB  - Intramolecular reductive coupling of cycloalkanones tethered to alkynoates in the
      presence of (eta(2)-propene)titanium was successfully performed to provide
      hydroxy-esters in a diastereoselective manner. Subsequent lactonization afforded
      angularly fused unsaturated tricyclic lactones which represent relevant
      substructures of numerous bioactive compounds.

PMID- 22407237
TI  - Clinicopathological and prognostic significance of microRNA-107 and its
      relationship to DICER1 mRNA expression in gastric cancer.
AB  - microRNAs (miRNAs) are small non-coding RNAs that regulate target gene
      expression. It is known that miRNA-107 (miR-107) promotes cancer invasion and
      metastasis. However, the relationship between clinicopathological factors and the
      prognostic significance of miR-107 for gastric cancer patients remains elusive.
      In this study, we evaluated the prognostic value of miR-107 using tissue samples
      from gastric cancer patients. Furthermore, the relationship between miR-107 and
      the mRNA levels of its target gene DICER1 was examined. The expression levels of
      miR-107 and DICER1 mRNA in tumor tissues and adjacent normal tissues of 161
      gastric cancer patients were examined (TNM stage I, 29 patients; stage II, 31
      patients; stage III, 51 patients and stage IV, 50 patients). miR-107 levels were
      measured by Taqman microRNA assays, and DICER1 mRNA levels were measured by the
      Taqman real-time RT-PCR method. In the analysis by real-time PCR-based miRNA
      arrays using pooled RNA samples from five gastric cancer patients, expression of
      miR-107, miR-21, miR-196a, miR-26b, miR-9, miR-142-3p, miR-30b, miR-150, miR-191
      and miR-17 was found to be upregulation. The mean expression level of miR-107 was
      significantly higher in the tumor tissues compared to that of normal tissues. In
      the comparison of clinicopathological factors, miR-107 expression showed
      significant association with depth of tumor invasion, lymph node metastasis and
      stage. In Kaplan-Meier survival curve analysis, overall survival rates (OS) and
      disease-free survival rates (DFS) of patients with high miR-107 expression were
      significantly worse than those of patients with low miR-107 expression. In the
      Cox multivariate analysis, it was shown that miR-107 expression in gastric cancer
      tissues was an independent prognostic factor for OS and DFS. Significant inverse
      correlations were demonstrated between miR-107 and DICER1 mRNA. Our results
      indicate that miR-107 may be useful as an effective biomarker for prediction of a
      poor prognosis in gastric cancer patients.

PMID- 22407235
TI  - Orbitofrontal cortex and impulsivity in borderline personality disorder: an MRI
      study of baseline brain perfusion.
AB  - Behavioral and neuroimaging studies in patients with borderline personality
      disorder (BPD) have associated orbitofrontal cortex (OFC) dysfunction with
      distinct symptom clusters such as impulsivity. It is unclear, however, whether
      abnormal patterns of OFC activity are also present during resting-state
      conditions and whether OFC dysfunction is specifically associated with
      impulsivity in BPD. This study tested the hypothesis that BPD patients would
      exhibit changes of OFC baseline perfusion and explored the relationship between
      regional cerebral blood flow and distinct BPD symptom clusters, such as
      impulsivity, dissociation tension and depressive symptoms. Using continuous
      arterial spin labeling magnetic resonance imaging at 3 Tesla, we investigated 16
      women with BPD according to DSM-IV criteria and 16 healthy female control
      participants during resting-state conditions. Between-group comparisons were
      conducted using an analysis of variance (p < 0.05 cluster corrected). Compared to
      controls, BPD patients exhibited decreased blood flow in the medial OFC, whereas
      increased blood flow was found in the left and right lateral OFC. Correlation
      analyses revealed a positive relationship between medial and lateral
      orbitofrontal blood flow and impulsivity scores, whereas measures of dissociation
      tension and depression did not exhibit a significant correlation with OFC
      perfusion. These data suggest that dysfunction of medial and lateral regions of
      the OFC could specifically mediate symptoms of impulsivity in BPD.

PMID- 22407238
TI  - Rapid fluorescent detection of neurogenin3 by CdTe quantum dot aggregation.
AB  - Here we report a facile immunoassay for detecting a synthetic peptide fragment of
      neurogenin3 (amino acid sequence: SKQRRSRRKKANDRERNRMH) by harnessing the
      aggregation-dependent fluorescence property of antibody-conjugated CdTe quantum
      dots in the presence of the target.

PMID- 22407239
TI  - Epidural test dose and tachycardia.

PMID- 22407240
TI  - Oral gastric tube-guided insertion of the ProSealTM laryngeal mask is an easy and
      noninvasive method for less experienced users.
AB  - PURPOSE: The ProSealTM laryngeal mask airway (PLMA) can be more difficult to
      insert than the classic laryngeal mask, especially in patients who have a thin
      palate with a steep oropharyngeal curve. Here, an oral gastric (OG) tube-guided
      technique is considered as a method that makes it easier to successfully insert a
      PLMA. METHODS: Sixty patients who were scheduled to undergo general anesthesia
      without neuromuscular blocking were randomly allocated into two groups: 30
      patients with PLMA inserted by the standard digital technique, and 30 with the
      PLMA inserted by an OG tube-guided technique. Most PLMA insertions were performed
      by less experienced users. The success rate at the first attempt, the time taken
      to insert the PLMA, the difficulty of the procedure, and the incidence of
      oropharyngeal trauma and postoperative sore throat were compared between the two
      groups. RESULTS: PLMA insertion was successfully achieved at the first attempt
      using the OG tube-guided technique in all 30 patients. The OG tube-guided
      insertion required fewer attempts (P = 0.04) and led to a less difficult
      insertion procedure (P = 0.02) than the standard digital insertion. Effective
      ventilation during anesthesia was achieved in all patients, with a lower mean
      cuff pressure in the OG tube-guided technique group (P = 0.02). The frequency of
      blood sticking to the PLMA tube (P < 0.001) and the incidence of postoperative
      sore throat (P = 0.003) were lower in the OG tube-guided group than the standard
      digital technique group. CONCLUSIONS: OG tube-guided PLMA insertion is easier for
      less experienced users, trainees, and experts as well as less invasive for
      patients than the standard digital insertion.

PMID- 22407241
TI  - A novel GATA6 mutation associated with congenital ventricular septal defect.
AB  - Ventricular septal defect (VSD) is the most common form of congenital
      cardiovascular malformation and an important contributor to the substantially
      increased morbidity and mortality in infants. Emerging evidence indicates the
      genetic basis for the pathogenesis of congenital VSD in a significant proportion
      of patients. However, congenital VSD is a genetically heterogeneous disease and
      the genetic defects responsible for VSD in the overwhelming majority of cases
      remain unclear. In this study, the entire coding region of the GATA6 gene, which
      encodes a zinc-finger transcription factor crucial to normal cardiogenesis, was
      sequenced in 130 unrelated patients with congenital VSD. The available relatives
      of the index patient carrying the identified mutation and 200 unrelated
      ethnically matched healthy individuals used as controls were subsequently
      genotyped. The functional characteristics of the mutant GATA6 were assessed in
      contrast to its wild-type counterpart using a luciferase reporter assay system.
      As a result, a novel heterozygous missense GATA6 mutation, p.G220S, was
      identified in a proband with VSD. The variation was absent in 400 control
      chromosomes and the altered amino acid was highly conserved evolutionarily across
      species. Genetic analysis of the family members of the mutation carrier showed
      that the substitution co-segregated with VSD was inherited as an autosomal
      dominant trait. Functional analysis demonstrated that the p.G220S mutation of
      GATA6 was associated with significantly decreased transcriptional activity. The
      findings provide novel insight into the molecular mechanism involved in VSD,
      implying the potential clinical implications in the gene-specific prophylaxis and
      therapy of this common developmental abnormality in neonates.

PMID- 22407242
TI  - A-class prostaglandins: early findings and new perspectives for overcoming tumor
      chemoresistance.
AB  - The antiproliferative properties of cyclopentenone prostaglandins of the A-class
      have long been known. Considerable research has led to the elucidation of some of
      the mechanisms of action of these pleiotropic compounds. A-class prostaglandins
      or derived molecules (A-PG) may block the cell cycle, inhibit anti-apoptotic
      transcription factors, activate apoptotic cascades, induce a stress response and
      inhibit protein synthesis in a cell type-dependent manner. In addition, recent
      reports indicate that A-class PG may interact with various cellular
      detoxification systems and drug metabolizing enzymes used by cancer cells as
      mechanisms of chemoresistance. Some of these findings may open new perspectives
      for the development of strategies aimed at overcoming cancer resistance to widely
      used antitumor drugs. Here we outline the mechanisms of action for the
      antitumoral effects of PGA and related compounds, emphasizing those with impact
      on cellular defence systems which may contribute to cancer chemoresistance. The
      ability of A-PG to form covalent adducts with thiol groups in proteins and in
      glutathione is essential for their biological actions. Therefore, identification
      of the protein targets and elucidation of the interactions of A-PG with the
      glutathione biotransformation system will be critical for understanding the
      antitumoral effects of these compounds per se or through their ability to
      sensitize cancer cells towards other drugs.

PMID- 22407243
TI  - Single cell ganglioside catabolism in primary cerebellar neurons and glia.
AB  - Cell-to-cell heterogeneity in ganglioside catabolism was determined by profiling
      fluorescent tetramethylrhodamine-labeled GM1 (TMR-GM1) breakdown in individual
      primary neurons and glia from the rat cerebellum. Cells isolated from 5 to 6 day
      old rat cerebella were cultured for 7 days, and then incubated for 14 h with TMR
      GM1. Intact cells were recovered from cultures by mild proteolysis,
      paraformaldehyde fixed, and subjected to single cell analysis. Individual cells
      were captured in a capillary, lysed, and the released single-cell contents
      analyzed by capillary electrophoresis with quantitative laser-induced fluorescent
      detection of metabolites. Non-neuronal cells on average took up much more
      exogenous TMR-GM1 than neuronal cells, and catabolized it more extensively. After
      14 h of incubation, non-neuronal cells retained only 14% of the TMR products as
      GM1 and GM2, compared to >50% for neurons. On average, non-neuronal cells
      contained 74% of TMR-labeled product as TMR-ceramide, compared to only 42% for
      neurons. Non-neuronal cells retained seven times as much TMR-GM3 (7%) compared to
      neuronal cells (1%). To confirm the observed single cell metabolomics, we lysed
      and compared TMR-GM1 catabolic profiles from mixed neuron/glial cell cultures and
      from cultures depleted of non-neuronal cells by treatment with the antimitotic
      agent cytosine arabinoside. The lysed culture catabolic profiles were consistent
      with the average profiles of single neurons and glia. We conclude that the
      ultrasensitive analytic methods described accurately reflect single cell
      ganglioside catabolism in different cell populations from the brain.

PMID- 22407245
TI  - [Controlling caesarean-site infection. Collaboration between the obstetric and
      hospital hygiene departments].
AB  - In 1998, the isolation of Staphylococcus aureus resistant to methicillin (MRSA)
      from a sample taken from a post-caesarean surgical site infection (SSI) led the
      obstetrics department to call upon the hospital hygiene team for assistance. A
      retrospective investigation of incidence in the files of 24 women with caesarean
      deliveries showed a SSI rate of 24%. These abnormally high figures led to an
      audit of hygiene practices during these deliveries. OBJECTIVES: To reduce the
      incidence of post-caesarean SSIs at Dreux Hospital Centre. MATERIALS AND METHODS:
      From 1999 through 2005, SSIs have been monitored according to the methods of the
      western France Coordinating Centre for Nosocomial Infections and the guidelines
      of ANAES in France and the U.S. CDC. The data were analysed by Epi Info 6,
      retrospectively. RESULTS: Files of 1972 caesareans performed over a 6-year period
      were analysed. The SSI rate was 24% in 1999; it fell to 7.4% in 2000 and
      stabilized from 2003 through 2005 in the neighbourhood of 2.6%. More than 70% of
      our patients are re-examined within 2 weeks of delivery. CONCLUSION: Close
      cooperation between the Obstetrics and Hospital Hygiene departments led to a
      dramatic reduction in SSI rates, to 2.6% (similar to the national rate), and its
      maintenance over a 3-year period. Implementation of the caesarean hygiene
      protocol has continued since 2006.

PMID- 22407244
TI  - The hypothesis on function of glycosphingolipids and ABO blood groups revisited.
AB  - Twenty-five years ago the author proposed new ideas of glycoprotein (GPs) and
      glycosphingolipid (GSLs) functions at the cell membrane. The GPs, apart from
      their glycan carrying capacity, were assumed to have specific, protein
      associated, functions. In contrast, GSLs such as those of globo and
      neolacto/lacto series, were considered to be energetically cheap membrane packing
      substances, filling in membrane spaces not covered with functional GPs. The
      terminal carbohydrate structures of the neolacto/lacto GSLs, i.e., sialic acid
      residues and ABH glycotopes, were postulated to have either regulatory or
      protective functions, respectively. A special active role was ascribed to
      terminal beta-galactosyl residues of GSLs and GPs. Gangliosides were considered
      to be functional GSLs. In the present review the author discusses these old ideas
      in context of the contemporary knowledge and comes to the conclusion that they
      have not aged.

PMID- 22407246
TI  - [Medical audit of neonatal deaths with the "three delay" model in a pediatric
      hospital in Ouagadougou].
AB  - OBJECTIVE: To determine the causes of neonatal deaths and their contributing
      factors. MATERIAL AND METHODS: We used the "three-delay model" to conduct an
      audit of the neonatal deaths that occurred between January 2006 and December 2010
      at the Charles de Gaulle University Pediatric Hospital, in Ouagadougou. RESULTS:
      The neonatal mortality rate was 12.3%. The main direct causes were infections
      (70%), cerebral distress (10%), respiratory distress (7%), congenital
      malformations (5.5%), prematurity (4.5%) and hemorrhagic syndromes (3%). All
      three delays were found: in decision making in 64.4% of cases, in access to
      health services in 77%, and in receiving appropriate care in 66.9%; they
      multiplied the risk of death by a factor of 4, 3 and 5, respectively. CONCLUSION:
      To reduce deaths of newborn babies, it is necessary to overcome the three delays
      that contribute to it, pending the improvement of socioeconomic conditions of
      populations. This combat requires optimizing the implementation of the subsidies
      for obstetric and neonatal emergency care and strengthening the involvement of
      all stakeholders, specifically, policy makers, the community and health
      professionals.

PMID- 22407247
TI  - [Epidemiology, microbiology, and outcomes of septicemia in children treated at
      the Charles de Gaulle University Pediatric Hospital in Burkina Faso].
AB  - The aim of this study is to describe the epidemiological and microbiological
      characteristics and outcome of children with septicemia at the Charles de Gaulle
      University Pediatric Hospital of Ouagadougou to help improve probabilistic
      antibiotic therapy in this type of infection. This retrospective descriptive
      study covered all the children from 0 to 15 years old seen over a period of 7
      years in any hospital department with suspected bacteriemia and for whom the
      bacteriology laboratory performed a blood culture. During the study period, the
      laboratory received 842 requests for blood cultures and found 154 (18.3%) of them
      to be positive. Files for 81 of the 154 patients could be found and examined. The
      distribution according to age showed septicemia was most frequent among those
      aged 6-15 years (61.7% of the cases). Microbial identification showed the
      dominant species to be Salmonella enterica (serovars paratyphi and typhi) (58%)
      followed by Staphylococcus aureus (12.3%). The salmonella isolates had a high
      rate of resistance to amoxicillin, chloramphenicol and cotrimoxazole.
      Staphylococci were always sensitive to the antibiotics with which they were
      tested, although to a lesser extent for penicillin G. All patients routinely
      received antibiotic treatment, and 81.5% (n=66) were cured (5 children died and
      10 left the hospital against medical advice). This study shows that the bacterial
      epidemiology of septicemia in our setting is dominated by salmonella. Trends in
      bacterial resistance to antibiotics showed that common antibiotics such as
      amoxicillin and cotrimoxazole are no longer acceptable as probabilist therapy
      here. They should be replaced in this type of infection by injectable third
      generation cephalosporin alone or combined with aminoglycosides.

PMID- 22407248
TI  - [Factors associated with overweight and obesity in children in Ouagadougou
      (Burkina Faso)].
AB  - INTRODUCTION: The international community is increasing concerned about obesity,
      which it has become one of the most common noninfectious pandemics worldwide and
      affects a growing number of children. MATERIAL AND METHODS: We conducted an
      analytic cross-sectional study from May 25 to June 16, 2010, among a sample of
      435 randomly selected students in secondary schools in the city of Ouagadougou to
      identify the factors contributing to obesity and overweight. RESULTS: The main
      factors significantly associated with obesity and overweight were family history
      of obesity (OR = 7.4), higher socioeconomic level (OR =  3.8), snacking on candy
      (OR = 5, 3), pastry (OR = 3.5), and chocolate (OR = 12.6), frequent consumption
      of sweets (OR = 2.2), lack of physical activity (OR = 4.4), and conflictual
      family relationships (OR = 3.9). CONCLUSION: Dealing with these factors in
      prevention activities should help to reduce the prevalence of overweight and
      obesity and their morbid consequences later on.

PMID- 22407249
TI  - [Cannabis use in a central region of Tunisia].
AB  - OBJECTIVE: The objective of this study was to determine the sociodemographic
      characteristics of cannabis users, their consumption patterns, and effects.
      METHODS: Our cross-sectional, descriptive study included 205 subjects (191 men,
      14 women, mean age = 25.9 +/- 7.9 years). The consumption of psychotropic drugs
      and/or cannabis was confirmed by toxicological analysis. RESULTS: In our study
      population, 61% were cannabis users. Consumption was significantly higher in
      males (94.4%) than in females. Consumers were young adults, aged 25.8 +/- 8.8
      years, single (81.6%), had primary school educations (62.4%), were employed (72%)
      and lived in urban areas (77.6%); 28.8% had a personal history of psychiatric
      disorders. The mean age of first cannabis use was 20 years. Cannabis use was
      frequently associated with consumption of alcohol and tobacco (72%). Forty
      percent of consumers used cannabis daily. Most of those who had used drugs had
      done so with friends. In most cases, cannabis was regarded as a means of escape
      from problems (29.3%), relaxation (20.2%), experimentation (18.2%) and a source
      of pleasure (16.7%). CONCLUSION: These data suggest the importance of primary
      prevention of early use and rapid treatment of young users.

PMID- 22407250
TI  - Galactosylated gelatin nanovectors of doxorubicin inhibit cell proliferation and
      induce apoptosis in hepatocarcinoma cells.
AB  - We have synthesized and characterized doxorubicin (DOX)-loaded galactosylated
      gelatin nanovectors using in vitro and in vivo for targeting liver cells
      including hepatocarcinoma cells. Galactosylated and nongalactosylated gelatin
      nanovectors (GL-GN-DOX and GN-DOX) were spherical in shape and had mean sizes of
      about 95.1 and 88.3 nm, respectively. In-vitro release of DOX from nanovectors
      followed first-order kinetics and was pH dependent. Galactosylated formulation
      released 95.2% of DOX compared with 86.6% by nongalactosylated formulation at pH
      5.8. However, the release rate was suppressed at pH 7.4. Further, we showed that
      GL-GN-DOX had greater growth inhibitory effect on HepG2 in terms of low
      inhibitory concentration (IC(50); 0.35 ug/ml) compared with GN-DOX (0.75 ug/ml)
      and induced caspase-3-mediated apoptosis in HepG2 cells. This might be due to
      efficient internalization of galactosylated nanovectors by HepG2 cells compared
      with unmodified formulation. Pharmacokinetic and biodistribution analyses show
      that galactosylated formulation deposits 24.5 ug/g of DOX in targeted tissue
      (liver) in comparison with heart (0.3 ug/g) at a single dose of 10 mg/kg. These
      results suggest that DOX-loaded galactosylated gelatin nanovectors warrant future
      in-depth antitumor study to scale-up technology and may be used for the
      management of hepatocarcinoma.

PMID- 22407251
TI  - Bevacizumab is an active agent for recurrent high-grade glioma, but do we need
      randomized controlled trials?
AB  - High-grade gliomas (HGGs), including glioblastoma, are a heterogeneous group of
      primary brain tumors, associated with devastating neurological sequelae and
      limited survival. In 2005, a randomized phase III study established postoperative
      radiotherapy and temozolomide as the standard of care for patients with resected,
      newly diagnosed glioblastoma. Despite this progress, almost all patients relapse
      and therapeutic options in the recurrent setting are limited. The optimum
      approach for recurrent HGG is challenging because of tumor resistance and the
      worsening performance status of the patients. As glioblastoma is a highly
      vascular tumor and has high levels of vascular endothelial growth factor, there
      has been interest in the use of the vascular endothelial growth factor targeting,
      monoclonal antibody bevacizumab. In a series of phase II studies, bevacizumab
      alone or with irinotecan showed improvements in tumor response, disease control,
      and survival compared with historical controls. These results led to the
      licensing of bevacizumab for glioblastoma in the USA, but a contrasting view was
      adopted by the European Medicines Agency, because of (deemed) modest response
      rates and lack of direct comparisons with other agents. Against this background,
      Gil and colleagues conducted a retrospective review of 130 patients with
      recurrent HGG treated with bevacizumab and irinotecan and showed an encouraging
      median progression-free survival of 5.1 months (95% confidence interval, 4.4-5.9)
      and a median overall survival of 9.0 months (95% confidence interval, 6.7-11.2),
      in agreement with other series. In this editorial, the context and implications
      of these results are discussed, with a particular focus on the possible need and
      design of randomized phase III trials.

PMID- 22407252
TI  - Change in iris parameters with physiological mydriasis.
AB  - PURPOSE: A pilot study to analyze the association of change in iris parameters
      with physiological mydriasis in angle closure eyes compared with normal control
      eyes among south Indian participants. METHODS: Sixteen eyes diagnosed with
      primary angle closure and 14 age, gender-matched open-angle control eyes were
      selected. All participants underwent anterior segment imaging using anterior
      segment optical coherence tomography in dim and bright illumination. The iris
      area (IA), iris volume (IV), and pupillary diameter were calculated using
      customized image processing software. RESULTS: The IA and IV were found to be
      lesser in angle closure compared with normal controls. Average IA (dim and
      bright) was found to be 3.4 and 3.7 mm(2) in normals and 3.03 and 3.35 mm(2) in
      angle closure, and average IV (dim and bright) was found to be 24.28 and 26.09
      mm(2) in normals and 21.38 and 22.6 mm(2) in angle closure. The IA and IV
      decreased significantly with pupillary dilation in normals and in angle closures.
      However, decrease in the IA (slope = 0.52 and 0.42; p = 0.012) and IV (slope =
      1.97 and 1.41; p = 0.014) with pupillary dilation was significantly higher in
      normals compared with angle closures, respectively. CONCLUSIONS: IA and IV were
      found to decrease as pupil dilates in normal and angle closure eyes among South
      Indians. Loss in the IV was found to be lower in angle closure eyes.

PMID- 22407253
TI  - Scene perception in age-related macular degeneration:  the effect of contrast.
AB  - PURPOSE: To investigate the effect of contrast on scene perception in people with
      age-related macular degeneration (AMD) and to examine the relationship between
      task performance and macular function. METHODS: Nineteen patients with AMD and
      visual acuity below 20/50 were compared with 16 normally sighted, age-matched
      controls. Complete ophthalmologic examination (visual acuity, intraocular
      pressure measurement, and funduscopy) was performed in both patients and
      controls. In addition, Pelli-Robson contrast sensitivity, fluorescein
      angiography, and visual field size were assessed in the AMD study patients. The
      stimuli were photographs of natural scenes containing or lacking an animal (the
      target). For each scene, the contrast of the original photograph was divided by
      2, 4, and 8 to yield versions with a residual contrast of 50, 25, and 12.5%,
      respectively. The four levels of contrast were presented randomly and
      participants were asked to press a key when they saw an animal. RESULTS: AMD
      patients exhibited a larger drop in target detection performance with the
      decrease in contrast than controls. We found a correlation between visual acuity
      and performance when the contrast was reduced to 50, 25, and 12.5% of the
      original value but not in the normal contrast condition. There were no
      correlations between letter contrast sensitivity, visual field lesion size, and
      performance. CONCLUSIONS: Our results suggest that optimal, stable contrast
      conditions would facilitate object recognition in everyday life for people with
      AMD.

PMID- 22407254
TI  - Optimal image sample size for corneal nerve morphometry.
AB  - PURPOSE: Arbitrary numbers of corneal confocal microscopy images have been used
      for analysis of corneal subbasal nerve parameters under the implicit assumption
      that these are a representative sample of the central corneal nerve plexus. The
      purpose of this study is to present a technique for quantifying the number of
      random central corneal images required to achieve an acceptable level of accuracy
      in the measurement of corneal nerve fiber length and branch density. METHODS:
      Every possible combination of 2 to 16 images (where 16 was deemed the true mean)
      of the central corneal subbasal nerve plexus, not overlapping by more than 20%,
      were assessed for nerve fiber length and branch density in 20 subjects with type
      2 diabetes and varying degrees of functional nerve deficit. Mean ratios were
      calculated to allow comparisons between and within subjects. RESULTS: In
      assessing nerve branch density, eight randomly chosen images not overlapping by
      more than 20% produced an average that was within 30% of the true mean 95% of the
      time. A similar sampling strategy of five images was 13% within the true mean 80%
      of the time for corneal nerve fiber length. CONCLUSIONS: The "sample combination
      analysis" presented here can be used to determine the sample size required for a
      desired level of accuracy of quantification of corneal subbasal nerve parameters.
      This technique may have applications in other biological sampling studies.

PMID- 22407255
TI  - SD-OCT use in myopic retinoschisis pre- and post-vitrectomy.
AB  - PURPOSE: To study the features of posterior retinoschisis in high myopia before
      and after vitrectomy and its correlation with the visual outcome by spectral
      domain optical coherence tomography (SD-OCT). METHODS: In this retrospective case
      series, 11 highly myopic eyes which underwent vitrectomy with internal limiting
      membrane peeling and gas tamponade for retinoschisis during June 2008 to December
      2009 were followed up for 6 months. Visual acuity and SD-OCT (Topcon 3D OCT-1000)
      examination were performed before surgery and 1, 3, and 6 months after surgery.
      RESULTS: Retinoschisis within the outer, middle, and inner layers was noted in
      six eyes, and foveal detachment was found in six eyes by SD-OCT preoperatively.
      The inner and outer segment junctions of the photoreceptor layer showed defects
      in all eyes. At 6 months postoperatively, the retina had reattached and schisis
      resolved in 10 eyes. Two parafoveal holes were noted in one eye after surgery.
      The best-corrected visual acuity increased from 0.15 to 0.8 in one eye, slightly
      improved in two eyes, and remained unchanged in eight eyes. The continuity of
      inner segment-outer segment layer almost completely recovered in the eye with
      best-corrected visual acuity of 0.8 while still showing defects in the other 10
      eyes. CONCLUSIONS: SD-OCT can clearly demonstrate the morphological changes of
      retinoschisis. It provides important evidence as to the advantage of vitrectomy
      with internal limiting membrane peeling and helps to explain the visual outcome
      by documenting the recovery of the inner segment-outer segment layer after
      surgery. An SD-OCT examination should be considered in patients with high myopia
      and decreasing vision, with no obvious fundoscopic findings.

PMID- 22407256
TI  - Do fenestrations affect the performance of orthokeratology lenses?
AB  - PURPOSE: To investigate the effect of lens fenestrations on the performance of
      orthokeratology lenses. METHODS: Twenty-two subjects (aged 11 to 31 years) were
      fitted with identical reverse geometry orthokeratology lenses in the two eyes.
      One eye was randomly designated to wear a lens with three 0.20 mm fenestrations
      at 120 degrees  intervals placed at the junction of the reverse and alignment
      curves. The lens for the other eye was not fenestrated. Subjects were reviewed at
      1 week, 1 month, 3 months, 6 months, and 1 year after fitting. Data were
      collected on refraction, visual performance, incidences and severity of corneal
      staining, lens binding, and corneal pigmented arc. RESULTS: Fifteen subjects
      achieved full correction in OU. There were no statistically significant
      differences in refractive and corneal changes, visual performance, incidences and
      severity of corneal staining and corneal pigmented arc formation between the two
      eyes. The incidence of lens binding was consistently higher in eyes wearing non
      fenestrated lenses but was not statistically significant. Severity of lens
      binding, however, was statistically significant at the 1-, 3-, 6- and 12-month
      visits, with the non-fenestrated lenses causing more severe binding. CONCLUSIONS:
      The addition of fenestrations to orthokeratology lenses has no effect on the
      efficacy of the treatment or outcomes in low to moderate myopic subjects.
      However, the severity of lens binding is reduced. Fenestrating reverse geometry
      lenses may be of assistance in cases where lens binding is a problem.

PMID- 22407257
TI  - Effects of reinforcer magnitude on response acquisition with unsignaled delayed
      reinforcement.
AB  - Sixteen rats received eight 1-h sessions of a tandem fixed-ratio 1 differential
      reinforcement-of-other-behavior 30-s schedule with reinforcer magnitude at one or
      six food pellet(s) across groups of eight rats. The larger reinforcer magnitude
      established the lever press more effectively. First, mean schedule completions
      differed across groups, in terms of both their overall difference and in their
      increase across sessions. Second, whereas the larger reinforcer magnitude
      established reliable response acquisition in all eight rats by the end of the
      experiment, the smaller reinforcer magnitude only established reliable response
      acquisition in four of eight rats. The present results systematically replicate
      earlier findings obtaining more reliable response acquisition with unsignaled
      delayed reinforcement with greater food deprivation. Taken together, this work
      demonstrates the influence of motivational variables on response acquisition with
      unsignaled delayed reinforcement.

PMID- 22407258
TI  - Comparison of basis functions for 3D PET reconstruction using a Monte Carlo
      system matrix.
AB  - In emission tomography, iterative statistical methods are accepted as the
      reconstruction algorithms that achieve the best image quality. The accuracy of
      these methods relies partly on the quality of the system response matrix (SRM)
      that characterizes the scanner. The more physical phenomena included in the SRM,
      the higher the SRM quality, and therefore higher image quality is obtained from
      the reconstruction process. High-resolution small animal scanners contain as many
      as 103-104 small crystal pairs, while the field of view (FOV) is divided into
      hundreds of thousands of small voxels. These two characteristics have a
      significant impact on the number of elements to be calculated in the SRM. Monte
      Carlo (MC) methods have gained popularity as a way of calculating the SRM, due to
      the increased accuracy achievable, at the cost of introducing some statistical
      noise and long simulation times. In the work presented here the SRM is calculated
      using MC methods exploiting the cylindrical symmetries of the scanner,
      significantly reducing the simulation time necessary to calculate a high
      statistical quality SRM and the storage space necessary. The use of cylindrical
      symmetries makes polar voxels a convenient basis function. Alternatively,
      spherically symmetric basis functions result in improved noise properties
      compared to cubic and polar basis functions. The quality of reconstructed images
      using polar voxels, spherically symmetric basis functions on a polar grid, cubic
      voxels and post-reconstruction filtered polar and cubic voxels is compared from a
      noise and spatial resolution perspective. This study demonstrates that polar
      voxels perform as well as cubic voxels, reducing the simulation time necessary to
      calculate the SRM and the disk space necessary to store it. Results showed that
      spherically symmetric functions outperform polar and cubic basis functions in
      terms of noise properties, at the cost of slightly degraded spatial resolution,
      larger SRM file size and longer reconstruction times. However, we demonstrate
      that post-reconstruction smoothing, usually applied in emission imaging to reduce
      the level of noise, can produce a spatial resolution degradation of ~50%, while
      spherically symmetric basis functions produce a degradation of only ~6%, compared
      to polar and cubic voxels, at the same noise level. Therefore, the image quality
      trade-off obtained with blobs is higher than that obtained with cubic or polar
      voxels.

PMID- 22407259
TI  - Teriparatide's role in the management of bisphosphonate-associated osteonecrosis
      of the jaw.

PMID- 22407260
TI  - Osteonecrosis and atypical fractures-common origins?

PMID- 22407261
TI  - Morphological changes in disc herniation in the lower cervical spine: an
      ultrastructural study.
AB  - INTRODUCTION: The basis of disc degeneration is still unknown, but is believed to
      be a cell-mediated process. Apoptosis might play a major role in degenerative
      disc disease (DDD). The aim of this study was to correlate the viability of disc
      cells with the radiological degeneration grades (rDG) in disc herniation.
      MATERIALS AND METHODS: Forty anterior IVD's (C4-C7) from 39 patients with DDD
      were studied histologically and ultrastructurally to quantify healthy, "balloon",
      chondroptotic, apoptotic and necrotic cells. Patients were classified to their
      rDG, as having either prolapse (P: DGII + III) and/or osteochondrosis (O: DGIV +
      V). Similar studies were undertaken on eight control discs. RESULTS: Cell death
      by necrosis (mean 35%) was common but differed not significantly in both groups.
      All patients with a disc prolapse DGII + III revealed balloon cells (iAF: mean
      32%). All appeared alive and sometimes were hypertrophic. However, significantly
      less balloon cells were found in the O-Group. Control samples revealed no
      evidence of "balloon" cells in DGII and only a minor rate in DGIII. CONCLUSION:
      According to the different rDG, quantitative changes were obvious in healthy and
      "balloon" cells, but not for cell death. At the moment it can only be
      hypothesized if "balloon" cells are part of a repair strategy and/or cause of
      disc herniation.

PMID- 22407262
TI  - Single level cervical fusion by an anterior approach using autologous bone graft
      influences the adjacent levels degenerative changes: clinical and radiographic
      results at 10-year minimum follow-up.
AB  - INTRODUCTION: Cervical degenerative pathology can produce pain and disability
      and, in case of failure of conservative treatment surgery is indicated. MATERIALS
      AND METHODS: 107 patients affected by single level cervical degenerative
      pathology were surgically treated by Cloward procedure. On radiographs, the
      sagittal segmental alignment (SSA) of the affected level and sagittal alignment
      of the cervical spine were measured. RESULTS: Preoperatively, mean SSA was 0.6
      degrees  and at the last follow-up 1.8 degrees . In particular, adjacent-level
      degeneration occurred more frequently in Group A than in Group B. CONCLUSION:
      Lordotic SSA angle can be considered a protective factor against adjacent-level
      degeneration.

PMID- 22407263
TI  - Treatment of typical amyelic somatic fractures with kyphoplasty and calcium
      phosphate cement: a critical analysis.
AB  - PURPOSE: Vertebroplasty and more recently kyphoplasty are recognized as
      techniques in the treatment of osteoporotic vertebral fractures and in case of
      pathological fracture like in secondary tumors. The recent introduction of
      calcium phosphate cement (CPC) that offers, at least theoretically, an
      osteointegrative capacity, absent in polymethyl methacrylate (PMMA), has
      generated interest for its use in the treatment of traumatic fractures (type A)
      even in young patients. METHODS: In this study, type A fractures without
      neurological signs were treated. A total of six male patients, of age between 21
      and 55 years (mean age 38 years), were included. Fracture treatment was performed
      with kyphoplasty with balloon (Kyphon) and injection of calcium phosphate cement
      for a total of seven procedures. RESULTS: The results were evaluated according to
      the regional kyphosis angle and the local kyphosis angle. The postoperative X-ray
      control showed an average improvement of the regional kyphosis angle of 7.4
      degrees ; however, this value was reduced by an average of 6.6 degrees  after 45
      days with regard to the postoperative control. The local kyphosis angle showed an
      average improvement of 9 degrees  at the postoperative control with an average
      worsening of 9.2 degrees  in the control after 45 days. CONCLUSIONS: While
      kyphoplasty with the use of CPC in the treatment of type A traumatic fractures
      was effective in the treatment of pain, it has not been so far effective
      concerning the maintenance of the reduction obtained intra-operatively and its
      osteointegrative effect.

PMID- 22407264
TI  - Neurological L5 burst fracture: posterior decompression and lordotic fixation as
      treatment of choice.
AB  - PURPOSE: We report our experience and literature review concerning surgical
      treatment of neurological burst fractures of the fifth lumbar vertebra. MATERIALS
      AND METHODS: Nineteen patients with L5 neurological burst fractures were
      consecutively enrolled; 6 patients had complete motor deficits, and 12 had
      sphincter dysfunction. We performed 18 posterior and one combined approaches. To
      avoid kyphosis, posterior internal fixation was achieved by positioning patients
      on the operating table with hips and knees fully extended. At the latest follow
      up (mean 22 months, range 10-66), neurological recovery, canal remodeling and L4
      S1 angle were evaluated. RESULTS: Vertebral body replacement was difficult, which
      therefore resulted in an oblique position of the cage. Vertebral bodies still
      remained deformed, even though fixation allowed for an acceptable profile (22
      degrees , range 20-35). We observed three cases of paralysis, five complete, and
      three incomplete recoveries. In the remaining eight patients, sphincter
      impairment was the only finding. In 15 patients, pain was absent or occasional;
      in four individuals, it was continuous but not invalidating. Remodeling was
      visible by X-ray and/or CT, without significant secondary stenosis. CONCLUSIONS:
      The L5 burst fractures are rare and mostly due to axial compression. Cauda and/or
      nerve root injuries are absolute indications for surgery. If an anterior approach
      is technically difficult, laminectomy can allow for decompression, and it can be
      easily combined with transpedicular screw fixation. Posterior instrumented
      fusion, also performed with the aim to restore sagittal profile, when associated
      with an accurate spinal canal exploration and decompression, may be looked at as
      an optimal treatment for neurological L5 burst fractures.

PMID- 22407265
TI  - Assessment of prognostic factors in patients with metastatic epidural spinal cord
      compression (MESCC) from solid tumor after surgery plus radiotherapy: a single
      institution experience.
AB  - PURPOSE: To identify potential prognostic factors predicting functional outcome
      and survival after surgery followed by radiotherapy for metastatic spinal cord
      compression due to solid tumors. METHODS: 531 consecutive patients with
      metastatic epidural spinal cord compression (MESCC) were treated at our
      institution. Surgery followed by radiation therapy was performed in 151 patients
      (30%) with various histological diagnoses. Three different surgical procedures
      were performed: minimal resection with or without instrumented fixation,
      curettage, and total tumorectomy. Within 1 month after surgery, RT was performed,
      delivering a total dose of 30-36 Gy (3 Gy per fraction). Ten potential prognostic
      factors were investigated for relationship with functional outcome and survival.
      RESULTS: Clinical remission of pain was obtained in 91% of patients and 94
      (62.5%) had recovery of neurological deficit. Recurrence in the same site of
      treatment occurred in nine (6%) patients. Median survival was 14 months (range 0
      52 months); OS at 1, 2, and 3 years was 43.6, 37, and 21.5%, respectively.
      Survival was significantly associated with the histology of primary tumor (P <
      0.001) and visceral metastases (P < 0.001) in the whole group; for histology, the
      prognostic factors statistically significant were other bone metastases in breast
      cancer, control of primary tumor, and the absence of visceral metastases in NSCLC
      and kind of surgery in the other. CONCLUSIONS: The key element for successful
      treatment of MESCC is multidisciplinary care of the patient, which includes all
      of those prognostic factors that have been, until now, analyzed and compared. In
      our set of patients treated for vertebral metastases, PS, time to development of
      symptoms, and the presence of visceral metastases affected functional outcome and
      survival.

PMID- 22407266
TI  - Sagittal profile control in patients affected by neurological scoliosis using
      Universal Clamps: a 4-year follow-up study.
AB  - PURPOSE: Patients affected by cerebral palsy often develop progressive scoliosis
      that can results in trunk instability with an impairment of both coronal and
      sagittal balance. The aim of this retrospective study was to demonstrate the
      ability of UC to control the sagittal profile in a consecutive series of patients
      affected by neurological scoliosis. METHODS: From 2006 to 2008, 84 patients (57
      F, 27 M) affected by neurological scoliosis were treated surgically. Mean age was
      14 years (range 10-17). The etiology was mainly cerebral palsy. The average pre
      operative Cobb angle was 73 degrees  +/- 16 degrees . Patients were divided into
      three groups according to the pre-operative presence of: physiological kyphosis
      (mean 29 degrees  +/- 8 degrees ), thoracic lordosis (mean 10 degrees  +/- 6
      degrees ) and hyperkyphosis (51 degrees  +/- 8 degrees ). A posterior access was
      performed in all patients using thoracic UC associated with transpedicular lumbar
      screws and a conventional claw at the upper extremity of the construct. RESULTS:
      The average percentage of coronal correction was 72%. In all three groups, we
      observed a common trend toward maintaining or restoring the physiological values.
      Mean follow-up time was 36 months. At the 1-year follow-up, the mean loss of
      correction was 7 degrees  +/- 2 degrees  in the coronal plane and 2 degrees  +/-
      1 degrees  in the sagittal plane with no other change thereafter. CONCLUSIONS:
      The hybrid construct using UC appears effective in neurological scoliosis
      treatment, providing a good correction of the deformity in both coronal and
      sagittal planes. In the present series, physiological thoracic kyphosis has been
      restored in all patients, providing better sitting tolerance in wheelchair-bound
      patients, and retaining standing and walking abilities in ambulatory patients.

PMID- 22407267
TI  - The anterior stand-alone approach (ASAA) during the acute phase of
      spondylodiscitis: results in 40 consecutively treated patients.
AB  - PURPOSE: Spondylodiscitis mainly affects the anterior part of the spine. In this
      paper, we retrospectively analyze our experience with the anterior stand-alone
      approach (ASAA) in the treatment of spinal infections. METHODS: Forty consecutive
      patients with severe spondylodiscitis underwent the ASAA during the acute
      infective phase. Treatment consisted of disease debridement, vertebral body
      reconstruction using titanium expandable prostheses and anterior fixation.
      RESULTS: There was neither mortality nor major morbidity. Successful arthrodesis
      was achieved in 39 out of 40 patients who remained disease free throughout the
      follow-up period. Six months after treatment, one patient experienced
      pseudarthrosis and required supplemented posterior spinal fixation for vertebral
      instability. However, adequate arthrodesis was eventually obtained even in this
      patient. CONCLUSIONS: ASAA with spine reconstruction using synthetic materials
      during the acute infection phase was safe and effective. The infections were
      rapidly defeated, the patients were allowed to stand up early after the procedure
      and the length of hospital stay was significantly reduced.

PMID- 22407268
TI  - Prediction of lower limb functional recovery after laminoplasty for cervical
      myelopathy: focusing on the 10-s step test.
AB  - OBJECTIVE: Operative decompression is indicated for progressive neurological
      deterioration in patients with cervical compressive myelopathy (CCM). However,
      the best timing to ensure clinical recovery has not been determined because of
      the lack of a suitable method. 10 s step ("step") test is an easily performed
      physical test to assess the severity of CCM, particularly for the severity of
      lower limb dysfunction. The purpose of this study was to analyze the predictive
      value of preoperative step test results in relation to the results of expansive
      laminoplasty in patients with CCM. MATERIALS AND METHODS: Clinical and imaging
      data were prospectively collected from 101 patients who underwent cervical
      expansive laminoplasty for CCM. The Japanese Orthopedic Association (JOA) score
      and the lower limb function section of the Japanese Orthopedic Association
      Cervical Myelopathy Evaluation Questionnaire (JOACMEQ-L) were used to evaluate
      surgical outcomes. Cutoff value was determined by receiver operating
      characteristic curve analysis to predict clinical recovery after surgery. JOA
      recovery rate exceeding 50% was defined as an effective clinical result. The
      treatment was judged to be effective in 30 patients based on the JOACMEQ-L. The
      cutoff value of the step test was 14.5 in cases of an effective judgment with JOA
      and JOACMEQ-L. Multivariate analysis showed that preoperative patient age and
      duration of symptoms were predictive parameters for effectively judging JOA
      scores. A preoperative step test result of greater than or equal to 14.5 and male
      gender were significant predictive parameters for an effective judgment with
      JOACMEQ-L. CONCLUSIONS: Preoperative step test results significantly reflected
      the effective results of JOACMEQ-L and were predictive of improved lower limb
      function after laminoplasty in patients with CCM. Patients with a score of
      greater than or equal to 14.5 can experience effective lower limb functional
      recovery.

PMID- 22407269
TI  - Quantifying subtle but persistent peri-spine inflammation in vivo to submicron
      cobalt-chromium alloy particles.
AB  - PURPOSE: We evaluated the consequences of cobalt-chromium alloy (CoCr) wear
      debris challenge in the peri-spine region to determine the inflammation and
      toxicity associated with submicron particulates of CoCr-alloy and nickel on the
      peri-spine. METHODS: The lumbar epidural spaces of (n = 50) New Zealand white
      rabbits were challenged with: 2.5 mg CoCr, 5.0 mg CoCr, 10.0 mg CoCr, a positive
      control (20.0 mg of nickel) and a negative control (ISOVUE-M-300). The CoCr-alloy
      and Ni particles had a mean diameter of 0.2 and 0.6 MUm, respectively. Five
      rabbits per dose group were studied at 12 and 24 weeks. Local and distant tissues
      were analyzed histologically and quantitatively analyzed immunohistochemically
      (TNF-alpha and IL-6). RESULTS: Histologically, wear particles were observed in
      all animals. There was no evidence of toxicity or local irritation noted during
      macroscopic observations in any CoCr-dosed animals. However, Ni-treated control
      animals experienced bilateral hind leg paralysis and were euthanized at Day 2.
      Histopathology of the Ni particle-treated group revealed severe neuropathy.
      Quantitative immunohistochemistry demonstrated a CoCr-alloy dose-dependent
      increase in cytokines (IL-6, TNF-alpha, p < 0.05) at 12 and 24 weeks.
      CONCLUSIONS: Subtle peri-spine inflammation associated with CoCr-alloy implant
      particles was dose dependent and persistent. Neuropathy can be induced by highly
      reactive Ni particles. This suggests peri-spine challenge with CoCr-alloy implant
      debris (e.g., TDA) is consistent with past reports using titanium alloy
      particles, i.e., mild persistent inflammation.

PMID- 22407270
TI  - Biomechanical evaluation of the Total Facet Arthroplasty System(r) (TFAS(r)):
      loading as compared to a rigid posterior instrumentation system.
AB  - PURPOSE: To gain insight into a new technology, a novel facet arthroplasty device
      (TFAS) was compared to a rigid posterior fixation system (UCR). The axial and
      bending loads through the implants and at the bone-implant interfaces were
      evaluated using an ex vivo biomechanical study and matched finite element
      analysis. Kinematic behaviour has been reported for TFAS, but implant loads have
      not. Implant loads are important indicators of an implant's performance and
      safety. The rigid posterior fixation system is used for comparison due to the
      extensive information available about these systems. METHODS: Unconstrained pure
      moments were applied to 13 L3-S1 cadaveric spine segments. Specimens were tested
      intact, following decompression, UCR fixation and TFAS implantation at L4-L5. UCR
      fixation was via standard pedicle screws and TFAS implantation was via PMMA
      cemented transpedicular stems. Three-dimensional 10 Nm moments and a 600 N
      follower load were applied; L4-L5 disc pressures and implant loads were measured
      using a pressure sensor and strain gauges, respectively. A finite element model
      was used to calculate TFAS bone-implant interface loads. RESULTS: UCR experienced
      greater implant loads in extension (p < 0.004) and lateral bending (p < 0.02).
      Under flexion, TFAS was subject to greater implant moments (p < 0.04). At the
      bone-implant interface, flexion resulted in the smallest TFAS (average = 0.20 Nm)
      but greatest UCR (1.18 Nm) moment and axial rotation resulted in the greatest
      TFAS (3.10 Nm) and smallest UCR (0.40 Nm) moments. Disc pressures were similar to
      intact for TFAS but not for UCR (p < 0.04). CONCLUSIONS: These results are most
      applicable to the immediate post-operative period prior to remodelling of the
      bone-implant interface since the UCR and TFAS implants are intended for different
      service lives (UCR--until fusion, TFAS--indefinitely). TFAS reproduced intact
      like anterior column load-sharing--as measured by disc pressure. The highest bone
      implant moment of 3.1 Nm was measured in TFAS and for the same loading condition
      the UCR interface moment was considerably lower (0.4 Nm). For other loading
      conditions, the differences between TFAS and UCR were smaller, with the UCR
      sometimes having larger values and for others the TFAS was larger. The long-term
      physiological meaning of these findings is unknown and demonstrates the need for
      a better understanding of the relationship between spinal arthroplasty devices
      and the host tissue as development of next generation motion-preserving posterior
      devices that hope to more accurately replicate the natural functions of the
      native tissue continues.

PMID- 22407272
TI  - Seasonality of reproduction of wild black-and-white snub-nosed monkeys
      (Rhinopithecus bieti) at Mt. Lasha, Yunnan, China.
AB  - Black-and-white snub-nosed monkeys (Rhinopithecus bieti) inhabit one of the
      harshest habitats by any nonhuman primate. Reliable predictive cues to initiate
      reproduction may be particularly critical for R. bieti because they inhabit such
      seasonally energetically challenging environments. To better understand the
      seasonal distribution of and predictive cues to reproduction, we collected
      breeding and birth data in a population of R. bieti at Mt. Lasha in Yunling
      Nature Reserve, Yunnan, China, from January 2008 to May 2010, using a combination
      of 10-min instantaneous scans and ad libitum observations. We examined variations
      in temperature, rainfall, and food availability, as well as photoperiod
      differences between Mt. Lasha and the more northerly Xiaochangdu to identify
      environmental influences on the timing of reproductive events. Our data show the
      area exhibited distinct seasonal fluctuations in rainfall, temperature, and food
      availability. Mating occurred year-round, but peaked in August, coinciding with
      the end of the period of highest temperatures and food availability, and during
      the peak rainfall. Copulation frequency peaked 1 month after corresponding peaks
      in staple foods, rainfall, and minimum temperatures, and 3-4 months after peaks
      in high-quality foods. Births were significantly seasonal, with a birth peak from
      mid-February to early April, and a mean birth date of 14 March. Eleven births
      occurred in 41 days in 2009, and 16 births occurred in 52 days in 2010. Births
      occurred during periods of increasing temperatures and food availability. Our
      findings are suggestive of at least one environmental control of conception
      timing, and support the notion that food availability during key reproductive
      stages is an ultimate factor for birth seasonality, but provide no supporting
      evidence for photoperiod during the conception season as a proximate cue to
      reproduction in R. bieti.

PMID- 22407271
TI  - Basic fibroblast growth factor in an animal model of spontaneous mammary tumor
      progression.
AB  - Although basic fibroblast growth factor (FGF2) was the first pro-angiogenic
      molecule discovered, it has numerous activities on the growth and differentiation
      of non-vascular cell types. FGF2 is both stimulatory and inhibitory, depending on
      the cell type evaluated, the experimental design used and the context in which it
      is tested. Here, we investigated the effects of manipulating endogenous FGF2 on
      the development of mammary cancer to determine whether its endogenous
      contribution in vivo is pro- or anti-tumorigenic. Specifically, we examined the
      effects of FGF2 gene dosing in a cross between a spontaneous breast tumor model
      (PyVT+ mice) and FGF2-/- (FGF KO) mice. Using these mice, the onset and
      progression of mammary tumors was determined. As predicted, female FGF2 WT mice
      developed mammary tumors starting around 60 days after birth and by 80 days, 100%
      of FGF2 WT female mice had mammary tumors. In contrast, 80% of FGF2 KO female
      mice had no palpable tumors until nearly three weeks later (85 days) at times
      when 100% of the WT cohort was tumor positive. All FGF KO mice were tumor-bearing
      by 115 days. When we compared the onset of mammary tumor development and the
      tumor progression curves between FGF het and FGF KO mice, we observed a
      difference, which suggested a gene dosing effect. Analysis of the tumors
      demonstrated that there were significant differences in tumor size depending on
      FGF2 status. The delay in tumor onset supports a functional role for FGF2 in
      mammary tumor progression, but argues against an essential role for FGF2 in
      overall mammary tumor progression.

PMID- 22407274
TI  - Diagnostic and ethical challenges in disorders of consciousness and locked-in
      syndrome: a survey of German neurologists.
AB  - Diagnosis and decisions on life-sustaining treatment (LST) in disorders of
      consciousness, such as the vegetative state (VS) and the minimally conscious
      state (MCS), are challenging for neurologists. The locked-in syndrome (LiS) is
      sometimes confounded with these disorders by less experienced physicians. We
      aimed to investigate (1) the application of diagnostic knowledge, (2) attitudes
      concerning limitations of LST, and (3) further challenging aspects in the care of
      patients. A vignette-based online survey with a randomized presentation of a VS,
      MCS, or LiS case scenario was conducted among members of the German Society for
      Neurology. A sample of 503 neurologists participated (response rate 16.4%). An
      accurate diagnosis was given by 86% of the participants. The LiS case was
      diagnosed more accurately (94%) than the VS case (79%) and the MCS case (87%, p <
      0.001). Limiting LST for the patient was considered by 92, 91, and 84% of the
      participants who accurately diagnosed the VS, LiS, and MCS case (p = 0.09).
      Overall, most participants agreed with limiting cardiopulmonary resuscitation; a
      minority considered limiting artificial nutrition and hydration. Neurologists
      regarded the estimation of the prognosis and determination of the patients'
      wishes as most challenging. The majority of German neurologists accurately
      applied the diagnostic categories VS, MCS, and LiS to case vignettes. Their
      attitudes were mostly in favor of limiting life-sustaining treatment and slightly
      differed for MCS as compared to VS and LiS. Attitudes toward LST strongly
      differed according to circumstances (e.g., patient's will opposed treatment) and
      treatment measures.

PMID- 22407275
TI  - Co-segregation of DM2 with a recessive CLCN1 mutation in juvenile onset of
      myotonic dystrophy type 2.
AB  - Myotonic dystrophy type 2 (DM2) is a common adult onset muscular dystrophy caused
      by a dominantly transmitted (CCTG)( n ) expansion in intron 1 of the CNBP gene.
      In DM2 there is no obvious evidence for an intergenerational increase of
      expansion size, and no congenital cases have been confirmed. We describe the
      clinical and histopathological features, and provide the genetic and molecular
      explanation for juvenile onset of myotonia in a 14-year-old female with DM2 and
      her affected mother presenting with a more severe phenotype despite a later onset
      of symptoms. Histological and immunohistochemical findings correlated with
      disease severity or age at onset in both patients. Southern blot on both muscle
      and blood samples revealed only a small increase in the CCTG repeat number
      through maternal transmission. Fluorescence in situ hybridization, in combination
      with MBNL1 immunofluorescence on muscle sections, showed the presence of mutant
      mRNA and MBNL1 in nuclear foci; the fluorescence intensity and its area appeared
      to be similar in the two patients. Splicing analysis of the INSR, CLCN1 and MBNL1
      genes in muscle tissue demonstrates that the level of aberrant splicing isoforms
      was lower in the daughter than in the mother. However, in the CLCN1 gene, a
      heterozygous mutation c.501C>G p.F167L was present in the daughter's DNA and
      found to be maternally inherited. Biomolecular findings did not explain the
      unusual young onset in the daughter. The co-segregation of DM2 with a recessive
      CLCN1 mutation provided the explanation for the unusual clinical findings.

PMID- 22407276
TI  - Early biomarkers for post-stroke cognitive impairment.
AB  - The aim of this study was to investigate whether some biomarkers could predict
      cognitive impairment after stroke. One hundred fifty-two first-ever stroke
      patients were recruited within 6-72 h after the onset of symptoms. Blood was
      drawn within 1 h after admission for determining biomarkers. Cognitive function
      was assayed 2 weeks after stroke. The patients were divided into four groups:
      stroke, vascular cognitive impairment with no dementia (VCIND), vascular dementia
      (VaD), and mixed dementia (MD). Forty healthy subjects were used as controls. The
      results indicated that lower soluble receptor levels for advanced glycation end
      products (sRAGE) and higher beta-secretase enzyme (BACE1) and neprilysin (NEP)
      levels were found in the VCIND, VaD, and MD groups. In addition, the percentages
      of epsilon3/epsilon4 genotypes and epsilon4 alleles in the VCIND, VaD, and MD
      groups were higher than in the stroke group. Correlation analysis determined that
      sRAGE, BACE1, and NEP were significantly related to the results of
      neuropsychological assessments. Logistic regression analysis, however, suggested
      that only sRAGE and BACE1 changed ahead of cognitive impairment after stroke. In
      conclusion, only BACE1 and sRAGE, not NEP or APOE genotypes, may be biomarkers
      diagnosing post-stroke cognitive impairment.

PMID- 22407277
TI  - Changes in sexual function and gonadal axis hormones after switching to
      aripiprazole in male schizophrenia patients:  a prospective pilot study.
AB  - Antipsychotic-induced sexual dysfunction is a common problem in patients with
      schizophrenia. The aim of the study was to investigate the effect of switching to
      aripiprazole on sexual dysfunction and the hypothalamic-pituitary-gonadal axis in
      male patients with schizophrenia. In this prospective, open-label study, the
      participants were 10 male schizophrenia patients treated with atypical
      antipsychotics, risperidone, amisulpride, and olanzapine. Before and after
      switching to aripiprazole, they were assessed on the Arizona Sexual Experience
      Scale, and hormonal levels were measured. Our results showed a significant
      improvement in the severity of sexual dysfunction, especially in 'ease of sexual
      arousal' and 'penile erection,' as measured by the Arizona Sexual Experience
      Scale total scores after switching to aripiprazole (chi(2) = 12.45 and P =
      0.002). The serum prolactin level decreased significantly after switching to
      aripiprazole (chi(2) = 11.14 and P = 0.004), but the changes in the total
      testosterone level were not significant (chi(2) = 4.75 and P = 0.93). Our results
      suggest that sexual dysfunction in schizophrenia patients seems to improve after
      switching to aripiprazole from other atypical antipsychotics (risperiodone,
      amisulpride, or olanzapine). This may be associated with a change in dopamine and
      serotonin transmissions and a decrease in the serum prolactin concentration.

PMID- 22407278
TI  - Prenatal and postpartum maternal psychological distress and infant development: a
      systematic review.
AB  - Infant development plays a foundational role in optimal child development and
      health. Some studies have demonstrated an association between maternal
      psychological distress and infant outcomes, although the main emphasis has been
      on postpartum depression and infant-maternal attachment. Prevention and early
      intervention strategies would benefit from an understanding of the influence of
      both prenatal and postpartum maternal distress on a broader spectrum of infant
      developmental outcomes. We conducted a systematic review of studies assessing the
      effect of prenatal and postpartum maternal psychological distress on five aspects
      of infant development: global; cognitive; behavioral; socio-emotional; and
      psychomotor. These findings suggest that prenatal distress can have an adverse
      effect on cognitive, behavioral, and psychomotor development, and that postpartum
      distress contributes to cognitive and socio-emotional development.

PMID- 22407280
TI  - Graphene-based electrochromic systems: the case of Prussian Blue nanoparticles on
      transparent graphene film.
AB  - Prussian Blue nanoparticles were electrodeposited on transparent grapheme film,
      which showed a promising electrochromism with response times in the range of 3.3
      38 s.

PMID- 22407279
TI  - The role of co-occurring disruptive behavior in the clinical presentation of
      children and adolescents with anxiety in the context of autism spectrum
      disorders.
AB  - This study explored the impact of disruptive behavior disorder (DBD) comorbidity
      on theoretically relevant correlates among 87 children and adolescents with
      autism spectrum disorders (ASD) and clinically significant anxiety. Relative to
      youth with ASD and anxiety alone, participants with ASD, anxiety, and DBD: (a)
      presented with significantly more severe anxiety symptoms per clinician-, parent
      , and self-report; (b) were more likely to be prescribed antipsychotic medication
      but were no more likely to receive additional psychosocial and educational
      interventions; and (c) experienced significantly greater functional impairment
      and family interference. These results suggest that co-occurring DBD in the
      context of ASD and anxiety confers greater risk for heightened symptom severity
      and functional impairment, and may be linked with increased prescription of
      antipsychotic medication.

PMID- 22407281
TI  - Preparation of highly polarized nuclear spin systems using brute-force and low
      field thermal mixing.
AB  - Over the years, several strategies have been developed for generating highly
      polarized nuclear spin systems, including dynamic nuclear polarization, optical
      pumping, and methods exploiting parahydrogen. Here, we present an alternative
      strategy, using an enhanced 'brute-force' approach (i.e. exposure to low
      temperatures and high applied magnetic fields). The main problem with this
      approach is that it may take an excessively long time for the nuclear
      polarization to approach thermal equilibrium at low temperatures, since nuclear
      relaxation becomes exceedingly slow due to the loss of molecular motion. We show
      that low-field thermal mixing can alleviate the problem by increasing the rate at
      which slowly-relaxing nuclei reach equilibrium. More specifically, we show that
      polarization can be transferred from a relatively rapidly relaxing (1)H reservoir
      to more slowly relaxing (13)C and (31)P nuclei. The effects are particularly
      dramatic for the (31)P nuclei, which in experiments at a temperature of 4.2 K and
      a field of 2 T show a 75-fold enhancement in their effective rate of approach to
      equilibrium, and an even greater (150-fold) enhancement in the presence of a
      relaxation agent. The mixing step is also very effective in terms of the amount
      of polarization transferred-70-90% of the maximum theoretical value in the
      experiments reported here. These findings have important implications for brute
      force polarization, for the problem becomes one of how to relax the solvent
      protons rather than individual more slowly-relaxing nuclei of interest. This
      should be a much more tractable proposition, and offers the additional attraction
      that a wide range of nuclear species can be polarized simultaneously. We further
      show that the (1)H reservoir can be tapped repeatedly through a number of
      consecutive thermal mixing steps, and that this could provide additional
      sensitivity enhancement in solid-state NMR.

PMID- 22407282
TI  - Anti-atherogenic activity of wild grape (Vitis thunbergii) extract antagonizing
      smooth muscle cell proliferation and migration promoted by neighboring
      macrophages.
AB  - The proliferation and migration of vascular smooth muscle cells (SMCs) play
      critical roles in intimal thickening and neointimal hyperplasia in early-phase
      atherosclerosis. This study tested whether wild grape extract (WGE) suppressed
      the proliferation and migration of human aortic SMCs induced by neighboring
      macrophages. Cellular expression of fibrogenic connective tissue growth factor
      (CTGF) and secretion of collagen IV and matrix metalloproteinase (MMP)-2 were
      determined in SMCs exposed to THP-1-differentiated macrophage-conditioned media.
      Proliferation was enhanced in SMCs exposed to macrophage-conditioned media
      collected during the early stage of differentiation, which was attenuated by
      treatment with >= 10 ug/ml WGE. Increased secretion of CTGF and collagen IV
      macrophage-conditioned media was suppressed in WGE-supplemented SMCs. TGF-beta1
      promoted production of CTGF and collagen IV was suppressed by blocking TGF-beta
      receptors of R1 and R2 in SMCs. WGE repressed macrophage-conditioned media
      upregulated MMP-2 secretion, indicating that WGE had an ability to encumber
      plaque rupture within atherosclerotic lesions. In addition, >= 1 ug/ml WGE
      ameliorated the migration of SMCs promoted by neighboring macrophages. These
      results demonstrate that WGE retarded neointimal hyperplasia and thickening
      within atherosclerotic plaques largely comprising of macrophages and SMCs.
      Therefore, WGE may be developed as an anti-proliferative and anti-migratory agent
      targeting SMCs in the proximity of newly differentiated and resident macrophages.

PMID- 22407283
TI  - Management of Cosmopolites sordidus and Metamasius hemipterus in banana by
      pheromone-based mass trapping.
AB  - Mass trapping Cosmopolites sordidus (Coleoptera, Curculionidae) using a pheromone
      baited pitfall trap and Metamasius hemipterus (Coleoptera, Curculionidae) using a
      pheromone-sugarcane-baited open gallon trap was conducted in commercial banana.
      Four traps for each insect per hectare were placed in each of two 5-hectare plots
      of banana. Two additional 5-hectare plots were designated as controls and treated
      according to the plantation protocol. Capture rates of C. sordidus and M.
      hemipterus declined by >75 % over 10-12 months. In the banana growing region
      studied, corm damage was due primarily to C. sordidus, while only a minor amount
      of damage was attributable to M. hemipterus. Corm damage reduction in trapping
      plots was, thus, attributed primarily to C. sordidus trapping. In trapping plots,
      corm damage decreased by 61-64 % during the experiment. Banana bunch weights
      increased 23 % relative to control plots after 11-12 months of trapping. Fruit
      diameter did not vary between bunches harvested from trapping plots vs. control
      plots. Plant vigor, however, as determined by stem circumference at one meter
      above ground increased in plots with traps compared to control plots. Trapping
      for C. sordidus in two plantations of over 200 hectares each, reduced corm damage
      62-86 % relative to pre-trapping levels. Insecticide control measures in place
      when the experiment commenced resulted in about 20-30 % corm damage, while use of
      pheromone trapping to manage C. sordidus lowered corm damage to 10 % or less. It
      is estimated that the increase in value of increased yield obtained in this trial
      (23 %) is about $4,240 USD per year per hectare, while the cost of pheromone
      trapping is approximately $185 USD per year per hectare. The trapping program
      becomes revenue neutral if bunch weights increase by an average of 1 % per year
      of trapping. Approximately 10 % of all plantation area in Costa Rica use the
      pheromone trapping system described here. The system also is used in Martinique,
      Guadeloupe, and the Canary Islands.

PMID- 22407284
TI  - Perspective.

PMID- 22407285
TI  - Comparison of equipressor doses of norepinephrine, epinephrine, and phenylephrine
      on septic myocardial dysfunction.
AB  - BACKGROUND: Myocardial depression is a frequent event during septic shock and may
      mimic a cardiogenic shock state with decreased cardiac output. Nevertheless, data
      are scarce regarding the myocardial effects of vasopressors used to treat
      hypotension. In this study, the authors compared the effects of three commonly
      used vasopressors acting on different adrenergic receptors on myocardial function
      in a rodent model of septic shock, as explored with conductance catheter and
      positron emission tomography. METHODS: Septic shock was induced in rats by
      peritonitis. Eighteen hours after septic insult, vasopressors were titrated to
      increase mean arterial pressure by 20% compared with baseline values. RESULTS: We
      observed that peritonitis was associated with arterial hypotension and
      systolodiastolic dysfunction. Norepinephrine and epinephrine improved mean
      arterial pressure, cardiac output, and preload recruitable stroke work, a load
      independent measure of systolic function, as well as diastolic function and
      ventriculoarterial coupling. Heart rate, myocardial oxygen consumption, and
      arrhythmia incidence were furthermore increased in the epinephrine group.
      Conversely, phenylephrine, a peripheral alpha-agonist, exhibited deleterious
      effects on systolodiastolic function and ventriculoarterial coupling. Conductance
      catheter and positron emission tomography yielded identical results with regard
      to myocardial function evolution under vasopressor treatment. CONCLUSIONS:
      Phenylephrine, a drug without beta-1 effects, was associated with decreased
      ventricular performance and ventriculoarterial uncoupling, whereas epinephrine
      and norepinephrine improved global hemodynamics and myocardial function in
      severely hypokinetic and hypotensive experimental septic shock. Nevertheless,
      epinephrine was associated with increased myocardial oxygen consumption. Thus,
      norepinephrine appears to be a more reliable and safer strategy as a first-line
      therapy in this particular setting.

PMID- 22407286
TI  - Molecular pathways regulating macrophage polarization: implications for
      atherosclerosis.
AB  - Recent years have seen a tremendous development of our insight into the biology
      of atherosclerosis and its acute thrombotic manifestations. Inflammation now
      takes center stage among traditional risk factors as a decisive factor in
      cardiovascular risk. Consequently, its assessment and modulation have become key
      to clinical care and fundamental research alike. Plaque macrophages orchestrate
      many of the inflammatory processes that occur throughout atherogenesis. These
      cells are characteristically heterogeneous and adopt diverse activation states in
      response to micro-environmental triggers. In this review, macrophage-mediated
      inflammation in atherosclerosis sets the scene for a discussion of the gene
      regulatory mechanisms that facilitate and shape polarized macrophage phenotypes.
      When applicable, we consider these factors within the context of atherosclerosis
      and reflect on opportunities for future application.

PMID- 22407287
TI  - Applications of human pharmacokinetic prediction in first-in-human dose
      estimation.
AB  - Quantitative estimations of first-in-human (FIH) doses are critical for phase I
      clinical trials in drug development. Human pharmacokinetic (PK) prediction
      methods have been developed to project the human clearance (CL) and
      bioavailability with reasonable accuracy, which facilitates estimation of a safe
      yet efficacious FIH dose. However, the FIH dose estimation is still very
      challenging and complex. The aim of this article is to review the common
      approaches for FIH dose estimation with an emphasis on PK-guided estimation. We
      discuss 5 methods for FIH dose estimation, 17 approaches for the prediction of
      human CL, 6 methods for the prediction of bioavailability, and 3 tools for the
      prediction of PK profiles. This review may serve as a practical protocol for PK-
      or pharmacokinetic/pharmacodynamic-guided estimation of the FIH dose.

PMID- 22407288
TI  - Challenges in development of nanoparticle-based therapeutics.
AB  - In recent years, nanotechnology has been increasingly applied to the area of drug
      development. Nanoparticle-based therapeutics can confer the ability to overcome
      biological barriers, effectively deliver hydrophobic drugs and biologics, and
      preferentially target sites of disease. However, despite these potential
      advantages, only a relatively small number of nanoparticle-based medicines have
      been approved for clinical use, with numerous challenges and hurdles at different
      stages of development. The complexity of nanoparticles as multi-component three
      dimensional constructs requires careful design and engineering, detailed
      orthogonal analysis methods, and reproducible scale-up and manufacturing process
      to achieve a consistent product with the intended physicochemical
      characteristics, biological behaviors, and pharmacological profiles. The safety
      and efficacy of nanomedicines can be influenced by minor variations in multiple
      parameters and need to be carefully examined in preclinical and clinical studies,
      particularly in context of the biodistribution, targeting to intended sites, and
      potential immune toxicities. Overall, nanomedicines may present additional
      development and regulatory considerations compared with conventional medicines,
      and while there is generally a lack of regulatory standards in the examination of
      nanoparticle-based medicines as a unique category of therapeutic agents, efforts
      are being made in this direction. This review summarizes challenges likely to be
      encountered during the development and approval of nanoparticle-based
      therapeutics, and discusses potential strategies for drug developers and
      regulatory agencies to accelerate the growth of this important field.

PMID- 22407289
TI  - Immunogenicity to therapeutic proteins: impact on PK/PD and efficacy.
AB  - The development of therapeutic proteins requires the understanding of the
      relationship between the dose, exposure, efficacy, and toxicity of these
      molecules. Several intrinsic and extrinsic factors contribute to the challenges
      for measuring therapeutic proteins in a precise and accurate manner. In addition,
      induction of an immune response to therapeutic protein results in additional
      complexities in the analysis of the pharmacokinetic profile, toxicity, safety,
      and efficacy of this class of molecules. Assessment of immunogenicity of
      therapeutic proteins is a required aspect of regulatory filings for a licensing
      application and for the safe and efficacious use of these compounds. A systematic
      strategy and well-defined criteria for measuring anti-drug antibodies (ADA) have
      been established, to a large extent, through coordinated efforts. These
      recommendations are based on risk assessment and include the determination of ADA
      content (concentration/titer), affinity, immunoglobulin isotype/subtype, and
      neutralization capacity. This manuscript reviews the requirements necessary for
      understanding the nature of an ADA response in order to discern the impact of
      immunogenicity on pharmacokinetics/pharmacodynamics and efficacy.

PMID- 22407290
TI  - Respiratory liver motion estimation and its effect on scanned proton beam
      therapy.
AB  - Proton therapy with active scanning beam delivery has significant advantages
      compared to conventional radiotherapy. However, so far only static targets have
      been treated in this way, since moving targets potentially lead to interplay
      effects. For 4D treatment planning, information on the target motion is needed to
      calculate time-resolved dose distributions. In this study, respiratory liver
      motion has been extracted from 4D CT data using two deformable image registration
      algorithms. In moderately moving patient cases (mean motion range around 6 mm),
      the registration error was no more than 3 mm, while it reached 7 mm for larger
      motions (range around 13 mm). The obtained deformation fields have then been used
      to calculate different time-resolved 4D treatment plans. Averaged over both
      motion estimations, interplay effects can increase the D5-D95 value for the
      clinical target volume (CTV) from 8.8% in a static plan to 23.4% when motion is
      considered. It has also been found that the different deformable registration
      algorithms can provide different motion estimations despite performing similarly
      for the selected landmarks, which in turn can lead to differing 4D dose
      distributions. Especially for single-field treatments where no motion mitigation
      is used, a maximum (mean) dose difference (averaged over three cases) of 32.8%
      (2.9%) can be observed. However, this registration ambiguity-induced uncertainty
      can be reduced if rescanning is applied or if the treatment plan consists of
      multiple fields, where the maximum (mean) difference can decrease to 15.2%
      (0.57%). Our results indicate the necessity to interpret 4D dose distributions
      for scanned proton therapy with some caution or with error bars to reflect the
      uncertainties resulting from the motion estimation. On the other hand, rescanning
      has been found to be an appropriate motion mitigation technique and, furthermore,
      has been shown to be a robust approach to also deal with these motion estimation
      uncertainties.

PMID- 22407291
TI  - Cone-rod dystrophy in Danon disease.

PMID- 22407292
TI  - Individual risk assessment and information technology to optimise screening
      frequency for diabetic retinopathy by Aspelund et al. (2011) Diabetologia 54:2525
      2532.

PMID- 22407293
TI  - The scleral rigidity of eyes with different refractions.
AB  - BACKGROUND: The weakened biomechanical properties of the sclera is an important
      feature of myopic eyes. The quantitative evaluation in vivo of posterior scleral
      resistance to the elongation remains a challenge. METHODS: This study comprised
      172 eyes from 86 subjects with a mean age of 20.6 years (range, 18-28 years).
      Ultrasound biometry was performed using an immersion technique and the A-scan
      device (the Biometer AL-1000 -TOMEY). The axial length of the eye was measured
      twice: before and during the application of an external pressure of 30 g on the
      eye. The difference between two mean values of AL measurements before and during
      the pressure application was considered as a degree of change in the axial length
      that resulted from the IOP elevation. The data were entered into an Excel
      spreadsheet (Microsoft Corp.) for subsequent analysis. Statistical analysis was
      performed using SigmaPlot software (version 11.0, Systat Software, Inc.). A value
      of 0.05 or less was considered statistically significant. RESULTS: The means +/-
      SD of axial changes before and during the external pressure for hyperopia,
      emmetropia, myopia 0.5-3.0 D, myopia 3.25-6.0 D, myopia 6.25-12.0 D and myopia
      over 12.0 D were as follows: 0.03 +/- 0.01 mm, 0.05 +/- 0.01 mm, 0.18 +/- 0.07
      mm, 0.31 +/- 0.02 mm, 0.38 +/- 0.07 mm, and 0.51 +/- 0.9 mm, respectively. The
      difference among groups was statistically significant. CONCLUSIONS: In
      conclusion, our study indicates that the biomechanical properties of the scleral
      coat, in terms of stretching and AL elongation, are measurable. The hypermetropic
      and emmetropic eyes possessed stiff sclera. The extent of AL remained practically
      unchanged during IOP elevation in these eyes. The absolute majority of the myopic
      eyes revealed a biomechanical weakness of the scleral shell. A higher degree of
      myopia was associated with increased AL elongation. Our approach to measuring the
      biomechanical properties of the sclera may have clinical significance in the
      future.

PMID- 22407294
TI  - Codanin-1, mutated in the anaemic disease CDAI, regulates Asf1 function in S
      phase histone supply.
AB  - Efficient supply of new histones during DNA replication is critical to restore
      chromatin organization and maintain genome function. The histone chaperone anti
      silencing function 1 (Asf1) serves a key function in providing H3.1-H4 to CAF-1
      for replication-coupled nucleosome assembly. We identify Codanin-1 as a novel
      interaction partner of Asf1 regulating S-phase histone supply. Mutations in
      Codanin-1 can cause congenital dyserythropoietic anaemia type I (CDAI),
      characterized by chromatin abnormalities in bone marrow erythroblasts. Codanin-1
      is part of a cytosolic Asf1-H3.1-H4-Importin-4 complex and binds directly to Asf1
      via a conserved B-domain, implying a mutually exclusive interaction with the
      chaperones CAF-1 and HIRA. Codanin-1 depletion accelerates the rate of DNA
      replication and increases the level of chromatin-bound Asf1, suggesting that
      Codanin-1 guards a limiting step in chromatin replication. Consistently, ectopic
      Codanin-1 expression arrests S-phase progression by sequestering Asf1 in the
      cytoplasm, blocking histone delivery. We propose that Codanin-1 acts as a
      negative regulator of Asf1 function in chromatin assembly. This function is
      compromised by two CDAI mutations that impair complex formation with Asf1,
      providing insight into the molecular basis for CDAI disease.

PMID- 22407295
TI  - Dehydration stress activates Arabidopsis MPK6 to signal DCP1 phosphorylation.
AB  - Eukaryotic mRNA decapping proteins are essential for normal turnover of mRNA.
      Yet, the mechanism of bulk mRNA turnover during stress responses and its
      importance to stress tolerance are poorly understood. Here, we showed that
      dehydration stress activated MPK6 to phosphorylate serine 237 of Arabidopsis DCP1
      and phospho-DCP1 preferentially associated with DCP5 to promote mRNA decapping in
      vivo. This process was essential for stress adaption as dcp5-1 and DCP1-S237A
      plants were hypersensitive to stress compared with wild-type (WT) plants.
      Microarray analysis revealed that dehydration-induced expression of many stress
      responsive genes was compromised in dcp5-1, whereas a subset of transcripts was
      over-represented in this mutant. Further analysis revealed that this subset of
      transcripts was likely the direct targets of stress-triggered mRNA decapping in
      WT. Our results suggest that mRNA decapping through MPK6-DCP1-DCP5 pathway serves
      as a rapid response to dehydration stress in Arabidopsis.

PMID- 22407296
TI  - Crystal structure of Cwc2 reveals a novel architecture of a multipartite RNA
      binding protein.
AB  - The yeast splicing factor Cwc2 contacts several catalytically important RNA
      elements in the active spliceosome, suggesting that Cwc2 is involved in
      determining their spatial arrangement at the spliceosome's catalytic centre. We
      have determined the crystal structure of the Cwc2 functional core, revealing how
      a previously uncharacterized Torus domain, an RNA recognition motif (RRM) and a
      zinc finger (ZnF) are tightly integrated in a compact folding unit. The ZnF plays
      a pivotal role in the architecture of the whole assembly. UV-induced crosslinking
      of Cwc2-U6 snRNA allowed the identification by mass spectrometry of six RNA
      contacting sites: four in or close to the RRM domain, one in the ZnF and one on a
      protruding element connecting the Torus and RRM domains. The three distinct
      regions contacting RNA are connected by a contiguous and conserved positively
      charged surface, suggesting an expanded interface for RNA accommodation. Cwc2
      mutations confirmed that the connector element plays a crucial role in splicing.
      We conclude that Cwc2 acts as a multipartite RNA-binding platform to bring RNA
      elements of the spliceosome's catalytic centre into an active conformation.

PMID- 22407299
TI  - microRNA-133 inhibits cell proliferation, migration and invasion in prostate
      cancer cells by targeting the epidermal growth factor receptor.
AB  - It has been shown that regulation of EGFR expression in prostate cancer cells is
      mostly at the transcriptional level. microRNA-133 (miR-133) has long been
      recognized as a muscle-specific miRNA which may regulate myoblast differentiation
      and participate in many myogenic diseases. Recently, it has been reported that
      miR-133 is also involved in other tumors, such as bladder cancer, esophageal
      cancer and may regulate cell motility in these cancer cells. In the present
      study, we examined the expression and effects of miR-133 in two hormone
      insensitive prostate cancer cell lines. The expression of miR-133a and miR-133b
      were analyzed by quantitative RT-PCR. After transfection of miR-133a and miR
      133b, cell viability assay, luciferase assay, western blot analysis, cell
      migration and invasion assay were conducted in Du145 and PC3 cells. In this
      study, we showed that miR-133a and miR-133b are expressed at the detection limit
      in two hormone-insensitive prostate cancer cell lines, PC3 and DU145. Ectopic
      expression of miR-133 inhibited cell proliferation, migration and invasion in
      these cells. We also provide the first evidence that miR-133 may target EGFR. Our
      study provided the first glimpse of the functional role of miR-133 in two hormone
      independent prostate cancer cell lines. These results may add to our knowledge on
      the molecular basis of prostate cancer progression.

PMID- 22407300
TI  - A combined quantum mechanics/molecular mechanics study of the one- and two-photon
      absorption in the green fluorescent protein.
AB  - We present for the first time a QM/MM study of the one- and two-photon absorption
      spectra of the GFP chromophore embedded in the full protein environment described
      by an advanced quantum mechanically derived polarizable force field. The
      calculations are performed on a crystal structure of the green fluorescent
      protein (GFP) using the polarizable embedding density functional theory (PE-DFT)
      scheme. The importance of treating the protein environment explicitly with a
      polarizable force field and higher-order multipoles is demonstrated, as well as
      the importance of including water molecules close to the chromophore in the
      protein barrel. For the most advanced description we achieve good agreement with
      experimental findings, with a peak at 405 nm for the neutral and a peak at 475 nm
      for the anionic form of the GFP chromophore. The presence of a dark OPA state, as
      suggested by other studies to explain the discrepancies between OPA and TPA
      spectra, is not supported by our calculations.

PMID- 22407297
TI  - Solution single-vesicle assay reveals PIP2-mediated sequential actions of
      synaptotagmin-1 on SNAREs.
AB  - Synaptotagmin-1 (Syt1) is a major Ca(2+) sensor for synchronous neurotransmitter
      release, which requires vesicle fusion mediated by SNAREs (soluble N
      ethylmaleimide-sensitive factor attachment protein receptors). Syt1 utilizes its
      diverse interactions with target membrane (t-) SNARE, SNAREpin, and
      phospholipids, to regulate vesicle fusion. To dissect the functions of Syt1, we
      apply a single-molecule technique, alternating-laser excitation (ALEX), which is
      capable of sorting out subpopulations of fusion intermediates and measuring their
      kinetics in solution. The results show that Syt1 undergoes at least three
      distinct steps prior to lipid mixing. First, without Ca(2+), Syt1 mediates
      vesicle docking by directly binding to t-SNARE/phosphatidylinositol 4,5
      biphosphate (PIP(2)) complex and increases the docking rate by 10(3) times.
      Second, synaptobrevin-2 binding to t-SNARE displaces Syt1 from SNAREpin. Third,
      with Ca(2+), Syt1 rebinds to SNAREpin, which again requires PIP(2). Thus without
      Ca(2+), Syt1 may bring vesicles to the plasma membrane in proximity via binding
      to t-SNARE/PIP(2) to help SNAREpin formation and then, upon Ca(2+) influx, it may
      rebind to SNAREpin, which may trigger synchronous fusion. The results show that
      ALEX is a powerful method to dissect multiple kinetic steps in the vesicle fusion
      pathway.

PMID- 22407301
TI  - Interference of engineered nanoparticles with in vitro toxicity assays.
AB  - Accurate in vitro assessment of nanoparticle cytotoxicity requires a careful
      selection of the test systems. Due to high adsorption capacity and optical
      activity, engineered nanoparticles are highly potential in influencing classical
      cytotoxicity assays. Here, four common in vitro assays for oxidative stress, cell
      viability, cell death and inflammatory cytokine production (DCF, MTT, LDH and IL
      8 ELISA) were assessed for validity using 24 well-characterized engineered
      nanoparticles. For all nanoparticles, the possible interference with the optical
      detection methods, the ability to convert the substrates, the influence on
      enzymatic activity and the potential to bind proinflammatory cytokines were
      analyzed in detail. Results varied considerably depending on the assay system
      used. All nanoparticles tested were found to interfere with the optical
      measurement at concentrations of 50 MUg cm-2 and above when DCF, MTT and LDH
      assays were performed. Except for Carbon Black, particle interference could be
      prevented by altering assay protocols and lowering particle concentrations to 10
      MUg cm-2. Carbon Black was also found to oxidize H2DCF-DA in a cell-free system,
      whereas only ZnO nanoparticles significantly decreased LDH activity. A dramatic
      loss of immunoreactive IL-8 was observed for only one of the three TiO2 particle
      types tested. Our results demonstrate that engineered nanoparticles interfere
      with classic cytotoxicity assays in a highly concentration-, particle- and assay
      specific manner. These findings strongly suggest that each in vitro test system
      has to be evaluated for each single nanoparticle type to accurately assess the
      nanoparticle toxicity.

PMID- 22407302
TI  - Vitamin D deficiency in HIV-infected and -uninfected women in the United States.

PMID- 22407303
TI  - TMP/SMX is still the preferred empiric antibiotic for methicillin-resistant
      Staphylococcus aureus skin and soft tissue infection in the HIV population.

PMID- 22407304
TI  - Community advisory boards in HIV research: current scientific status and future
      directions.

PMID- 22407305
TI  - Direct-to-Consumer genetic testing: what are we talking about?
AB  - The term Direct-to-Consumer (DTC) genetic testing refers to many different
      categories of testing. This editorial addresses the issues related to DTC testing
      for large effect and small effect variants associated with disease. In
      particular, there are issues of clinical validity and utility, informativeness
      and residual risk. Genetic counselors are poised to address these issues because
      of their training in probability and statistical models. The authors suggest that
      genetic counselors can impact the general public's understanding of DTC test
      results by: including evaluation of DTC concepts in graduate program curricula,
      holding AEC plenary sessions about emerging DTC concepts, and helping other
      professionals understand DTC concepts. Importantly, genetic counselors are
      advised to continue doing and promoting rigorous research on how people access
      and use DTC genetic testing and results, as well as gathering empirical data so
      that discussions of harms and benefits can go beyond theory. It is our hope that
      genetic counselors in practice will continue to critically evaluate claims made
      about emerging new tests, including those marketed DTC, in order to provide the
      best possible services to our patients.

PMID- 22407306
TI  - Understanding of genetic inheritance among Xhosa-speaking caretakers of children
      with hemophilia.
AB  - Hemophilia A and B are X-linked recessive inherited bleeding disorders that have
      a profound impact on the family of affected individuals. Education is vital to
      enable women to appreciate the implications of being a carrier and the
      implications for a prospective child. Prior research has shown that cultural,
      socio-economic and linguistic issues in South Africa are major barriers to
      communication for first-language Xhosa-speakers. This exploratory study aimed to
      investigate the basic knowledge of genetic inheritance among this cultural group
      in order to promote culturally-sensitive, effective genetic counseling. Ten in
      depth interviews were conducted with Xhosa-speaking mothers or caregivers of boys
      with hemophilia. Results suggest that the participants had a very limited
      understanding of the clinical management, genetic consequences and cause of
      hemophilia. While treatment and care by health care service providers was fully
      accepted, several participants believed that traditional methods would provide
      them with more satisfactory explanations. These findings suggest that there is a
      critical need for socio-culturally tailored, language-specific education for
      families with hemophilia.

PMID- 22407307
TI  - Pretreatment with Mycobacterium avium-derived lipids attenuates the response of
      murine macrophages to components of Mycobacterium tuberculosis.
AB  - The high prevalence of Mycobacterium tuberculosis (MTB) despite widely available
      Bacille Calmette-Guerin (BCG) vaccination may be associated with Mycobacterium
      avium (M. avium), which may influence the host response to MTB. In this study, we
      demonstrate that pretreatment of murine macrophages with low-dose Mycobacterium
      avium-derived lipids (MALs), but not Escherichia coli-derived lipids (ELs),
      attenuates the clearance of intracellular Mycobacterium bovis BCG (M. bovis BCG)
      and the production of TNF-alpha, IL-6, IL-12 and nitric oxide (NO) following
      stimulation with purified protein derivatives (PPD) or heat-inactivated M. bovis
      BCG in vitro. Furthermore, a significant decrease in NF-kappaB activity was
      observed in MALs-pretreated RAW264.7 cells that were co-transfected with pSV-beta
      galactosidase and pGL4.32[luc2P/NF-kappaB-RE/Hygro] prior to stimulation with PPD
      or heat-inactivated M. bovis BCG. In contrast, IRAK-M, an inhibitor of NF-kappaB
      activation, was increased in these cells. This observed hyporesponsiveness is not
      related to the expression of Toll-like receptor 2 (TLR2). In conclusion,
      pretreatment with low-dose MALs can induce hyporesponsiveness to MTB components
      in murine macrophages.

PMID- 22407308
TI  - Juvenile toxicity: are we asking the right questions?
AB  - The recent increase in numbers of juvenile toxicity studies over the past few
      years has doubtless added to our knowledge of the development of organ systems in
      the young rodent, but it is perhaps rather more difficult to answer the questions
      as to whether this body of work has served us well in terms of assessing risk in
      the pediatric population. If there are shortcomings, are they the result of poor
      study design or poor sensitivity of the model, or are the wrong questions being
      posed? This article provides a superficial overview of the progress made thus far
      and considers which aspects of study design and model choice currently fail to
      adequately address the major issues surrounding pediatric toxicology.

PMID- 22407309
TI  - Regulatory forum opinion piece: blind reading of histopathology slides in general
      toxicology studies.
AB  - With the intention of reducing bias, a recent European Food Safety Authority
      draft guidance document included a recommendation for blinded evaluation of
      histopathology slides in general toxicology studies (EFSA 2011). Although
      blinding as to treatment status reduces bias in many types of scientific
      experiment and is sometimes also appropriate in toxicologic pathology (Holland
      and Holland 2011), it is most unlikely to help achieve the overall goal of
      improved human safety when used for routine histopathology evaluation of tissues
      in general toxicology studies. This is the case because (1) blinding is not
      applicable to the inductive reasoning process used to identify test article
      effects in the tissues and would dramatically reduce the chances of these being
      successfully identified; and (2) in any case, the bias that would be reduced by
      blinding is actually a bias favoring diagnosis of a toxicological hazard and a
      conservative safety evaluation, which is appropriate in this context. Other
      unintended consequences of blinding histopathology evaluation include reductions
      in sensitivity for a variety of additional reasons and increased subjectivity of
      the pathology data.

PMID- 22407310
TI  - miR-200c inhibits invasion and migration in human colon cancer cells SW480/620 by
      targeting ZEB1.
AB  - MicroRNAs are a class of ~22-nt noncoding single-strand RNAs regulating gene
      expression postscriptionally. Metastasis caused poor prognosis in colorectal
      cancer patients and half of the patients developed metastatic lesions when
      admission. Here we investigated the possible roles of microRNAs in regulating
      metastasis in the paired colon cancer cells SW480 and SW620. Among those
      dysregulated microRNAs, miR-200c was speculated to inhibit metastasis by
      targeting ZEB1. Overexpression of miR-200c was concurrent with downregulation of
      ZEB1 mRNA and protein. Functional assays demonstrated that modulation of miR-200c
      with mimics or inhibitors changed potential of metastasis in SW480/620 cancer
      cells in vitro. Taken together, our study demonstrated that miR-200c inhibits
      metastatic ability by targeting ZEB1 in colon cancer cells SW480/620 and
      suggested that modulation of miR-200c could serve as therapeutic tool for
      inhibiting metastasis in colorectal cancer.

PMID- 22407311
TI  - Robotic transaxillary thyroid lobectomy of a follicular neoplasm.
AB  - PURPOSE: Minimally invasive thyroid surgery using various techniques is well
      described. The purpose of this video is to show a robotic-assisted transaxillary
      right thyroid lobectomy for a follicular neoplasm with intraoperative nerve
      monitoring and stimulation of recurrent laryngeal nerve. Herein, we show our
      experience with the technique and its safety and feasibility. METHODS: We
      performed a right thyroid lobectomy on a 33-year-old patient using the da Vinci
      Si-HD Surgical System. The operation was done via a single axillary incision, 5
      cm in length. The flap creation time was approximately 26 min. The robot docking
      time was 6 min. The recurrent laryngeal nerve was identified and nerve
      stimulation was used to stimulate with 0.5 milliamps. The operative console time
      was 21 min. Total operative time was 69 min. RESULTS: The procedure was
      successfully completed. Blood loss was minimal. Postoperative laryngoscopy showed
      intact and mobile bilateral vocal cords. There were no complications. Patient was
      discharged 4 h after surgery. CONCLUSIONS: Robotic transaxillary endoscopic
      gasless thyroid surgery with monitoring and stimulation of the RLN is feasible
      and safe. This technique eliminates a visible neck scar and affords excellent
      high definition optics of the cervical anatomy. This new technique can be
      accomplished on an outpatient basis.

PMID- 22407312
TI  - MicroRNA-10a is overexpressed in human pancreatic cancer and involved in its
      invasiveness partially via suppression of the HOXA1 gene.
AB  - BACKGROUND: There is increasing evidence that microRNAs are differentially
      expressed in many types of cancers. Despite progress in analyses of microRNAs in
      several types of cancers, the functional contributions of microRNAs to pancreatic
      cancer remain unclear. METHODS: In the present study, the expression levels of
      specific microRNAs identified by microarray analyses were examined in a panel of
      15 pancreatic cancer cell lines. We then investigated the functional roles of
      these microRNAs in the proliferation and invasion of pancreatic cancer cells.
      RESULTS: Based on the microarray data, we found frequent and marked
      overexpression of miR-10a, miR-92, and miR-17-5p in pancreatic cancer cell lines.
      Microdissection analyses revealed that miR-10a was overexpressed in pancreatic
      cancer cells isolated from a subset of primary tumors (12 of 20, 60%) compared
      with precursor lesions and normal ducts (P<.01). In vitro experiments revealed
      that miR-10a inhibitors decreased the invasiveness of pancreatic cancer cells
      (P<.01), but had no effect on their proliferation. Inhibition of HOXA1, a target
      of miR-10a, promoted the invasiveness of pancreatic cancer cells (P<.01).
      CONCLUSIONS: The present data suggest that miR-10a is overexpressed in a subset
      of pancreatic cancers and is involved in the invasive potential of pancreatic
      cancer cells partially via suppression of HOXA1.

PMID- 22407313
TI  - Endoscopic tumor length is an independent prognostic factor in esophageal
      squamous cell carcinoma.
AB  - PURPOSE: To investigate the impact of endoscopic esophageal tumor length on
      survival for patients with resected esophageal squamous cell carcinoma (ESCC).
      METHODS: We retrospectively reviewed the clinicopathologic characteristics of 244
      ESCC patients who underwent curative resection as the primary treatment at Taipei
      Veterans General Hospital between January 2000 and November 2010. The endoscopic
      tumor length was defined as a uniform measurement before completion of the
      esophagectomy. The impact of endoscopic tumor length on a patient's overall
      survival (OS) and disease-free survival (DFS) were assessed. A Cox regression
      model was used to identify prognostic factors. RESULTS: The 1-, 3-, and 5-year OS
      rates were 81.2, 48.2, and 39.6%, respectively, with a median survival time of
      18.0 months. The 1-, 3-, and 5-year DFS rates were 66.2, 34.7, and 32.4%,
      respectively, with a median DFS of 15.0 months. Endoscopic tumor length
      correlated with pathologic tumor length [Pearson correction (r)=0.621; P<0.001]
      Regression trees analyses suggested an optimum cutoff point of >4 cm to identify
      patients with decreased long-term survival. In multivariate survival analysis,
      endoscopic tumor length (more or less than 4 cm) remained an independent
      prognostic factor for both OS (P=0.006) and DFS (P=0.002). CONCLUSIONS:
      Endoscopic tumor length could have a significant impact on both the OS and DFS of
      patients with resected ESCC and may provide additional prognostic value to the
      current tumor, node, and metastasis staging system before patients receive any
      cancer-specific treatment.

PMID- 22407315
TI  - Measuring effort in neuropsychological evaluations of forensic cases of Spanish
      speakers.
AB  - Changing demographics indicate a dramatic growth in Spanish speakers in the USA.
      There is an increasing need to provide valid neuropsychological evaluations to
      these individuals as well as interest in providing the same in Latin American
      countries. This is especially the case with symptom validity testing, in general,
      and those involved with litigation in particular. To address this situation, the
      Dot Counting Test, the Rey 15-Item Test, and the Test of Memory Malingering were
      administered to clinical controls as well as individuals involved in litigation
      forensic non-capital and forensic capital murder cases. The results represent a
      first step toward the determination of the utility of those tests to address
      effort in Spanish speakers in the USA.

PMID- 22407314
TI  - Immunohistochemical evidence of the prognostic value of hedgehog pathway
      components in primary gallbladder carcinoma.
AB  - PURPOSE: The activation of hedgehog (Hh) pathways has been studied extensively in
      many malignant tumors to elucidate their clinical diagnostic and prognostic
      utilities. However, their roles in primary gallbladder carcinoma (GBC) remain
      poorly understood. This study was conducted to clarify the immunoreactivity and
      prognostic value of Hh pathway components in GBC. METHODS: Levels of sonic
      hedgehog (Shh), its receptor, Patched (Ptch1), and its downstream transcription
      factor, Gli1 protein, were measured by immunohistochemistry in 93 specimens from
      patients with GBC. We analyzed the correlations between the expression of these
      factors and clinicopathological features, including prognosis. RESULTS: Among the
      93 GBC specimens, 76 (81.7%), 70 (75.3%) and 66 (70.0%) were positive for Shh,
      Ptch1 and Gli1 expression, respectively. Expressions were significantly
      correlated with stage, lymph node metastasis, venous invasion, hepatic
      infiltration and lymphatic invasion (all P < 0.05). Patients with positive
      staining for Shh, Ptch1 and Gli1 had significantly lower survival rates than
      patients with negative staining. The expression patterns of Shh, Ptch1 and Gli1
      were all associated with a malignant behavior risk category in GBC. CONCLUSIONS:
      To our knowledge, this is the first report to define the role of the Hh pathway
      in GBC. Shh, Ptch1 and Gli1 are frequently expressed in GBC and associated with
      poorer survival. Thus, high expressions of Shh, Ptch1 and Gli1 proteins could
      serve as auxiliary parameters for predicting the malignant behavior of GBC.

PMID- 22407316
TI  - Unique emission from norbornene derived terpyridine--a selective chemodosimeter
      for G-type nerve agent surrogates.
AB  - A new chemodosimeter for a G-type agent that exploits norbornene derived
      terpyridine (NDT)-lanthanide unique emission is reported. The unusual emission
      between terpyridine and norbornene motifs of NDT is attributed to the significant
      difference in the position of the HOMO and LUMO wave functions that prevents the
      non-radiative relaxation pathway. An interesting magenta emission from NDT along
      with Eu(III) is utilized as a new fluorometric chemodosimeter that selectively
      detects (by changing the observed magenta emission to blue) G-type agent
      surrogates. A detection limit of 40 ppb is obtained and the selectivity for
      reactive surrogates over a variety of other close chemical analogs is
      demonstrated.

PMID- 22407317
TI  - Structure and mechanism of a glutamate-GABA antiporter.
AB  - Food-borne hemorrhagic Escherichia coli, exemplified by the strains O157:H7 and
      O104:H4 (refs 1, 2), require elaborate acid-resistance systems (ARs) to survive
      the extremely acidic environment such as the stomach (pH ~ 2). AR2 expels
      intracellular protons through the decarboxylation of L-glutamate (Glu) in the
      cytoplasm and exchange of the reaction product gamma-aminobutyric acid (GABA)
      with extracellular Glu. The latter process is mediated by the Glu-GABA antiporter
      GadC, a representative member of the amino-acid-polyamine-organocation
      superfamily of membrane transporters. The functional mechanism of GadC remains
      largely unknown. Here we show, with the use of an in vitro proteoliposome-based
      assay, that GadC transports GABA/Glu only under acidic conditions, with no
      detectable activity at pH  values higher than 6.5. We determined the crystal
      structure of E. coli GadC at 3.1 A resolution under basic conditions. GadC,
      comprising 12 transmembrane segments (TMs), exists in a closed state, with its
      carboxy-terminal domain serving as a plug to block an otherwise inward-open
      conformation. Structural and biochemical analyses reveal the essential transport
      residues, identify the transport path and suggest a conserved transport mechanism
      involving the rigid-body rotation of a helical bundle for GadC and other amino
      acid antiporters.

PMID- 22407318
TI  - Tissue factor and PAR1 promote microbiota-induced intestinal vascular
      remodelling.
AB  - The gut microbiota is a complex ecosystem that has coevolved with host
      physiology. Colonization of germ-free (GF) mice with a microbiota promotes
      increased vessel density in the small intestine, but little is known about the
      mechanisms involved. Tissue factor (TF) is the membrane receptor that initiates
      the extrinsic coagulation pathway, and it promotes developmental and tumour
      angiogenesis. Here we show that the gut microbiota promotes TF glycosylation
      associated with localization of TF on the cell surface, the activation of
      coagulation proteases, and phosphorylation of the TF cytoplasmic domain in the
      small intestine. Anti-TF treatment of colonized GF mice decreased microbiota
      induced vascular remodelling and expression of the proangiogenic factor
      angiopoietin-1 (Ang-1) in the small intestine. Mice with a genetic deletion of
      the TF cytoplasmic domain or with hypomorphic TF (F3) alleles had a decreased
      intestinal vessel density. Coagulation proteases downstream of TF activate
      protease-activated receptor (PAR) signalling implicated in angiogenesis. Vessel
      density and phosphorylation of the cytoplasmic domain of TF were decreased in
      small intestine from PAR1-deficient (F2r(-/-)) but not PAR2-deficient (F2rl1(-/
      )) mice, and inhibition of thrombin showed that thrombin-PAR1 signalling was
      upstream of TF phosphorylation. Thus, the microbiota-induced extravascular TF
      PAR1 signalling loop is a novel pathway that may be modulated to influence
      vascular remodelling in the small intestine.

PMID- 22407319
TI  - The Shigella flexneri effector OspI deamidates UBC13 to dampen the inflammatory
      response.
AB  - Many bacterial pathogens can enter various host cells and then survive
      intracellularly, transiently evade humoral immunity, and further disseminate to
      other cells and tissues. When bacteria enter host cells and replicate
      intracellularly, the host cells sense the invading bacteria as damage-associated
      molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) by
      way of various pattern recognition receptors. As a result, the host cells induce
      alarm signals that activate the innate immune system. Therefore, bacteria must
      modulate host inflammatory signalling and dampen these alarm signals. How
      pathogens do this after invading epithelial cells remains unclear, however. Here
      we show that OspI, a Shigella flexneri effector encoded by ORF169b on the large
      plasmid and delivered by the type IotaIotaIota secretion system, dampens acute
      inflammatory responses during bacterial invasion by suppressing the tumour
      necrosis factor (TNF)-receptor-associated factor 6 (TRAF6)-mediated signalling
      pathway. OspI is a glutamine deamidase that selectively deamidates the glutamine
      residue at position 100 in UBC13 to a glutamic acid residue. Consequently, the E2
      ubiquitin-conjugating activity required for TRAF6 activation is inhibited,
      allowing S. flexneri OspI to modulate the diacylglycerol-CBM (CARD-BCL10-MALT1)
      complex-TRAF6-nuclear-factor-kappaB signalling pathway. We determined the 2.0 A
      crystal structure of OspI, which contains a putative cysteine-histidine-aspartic
      acid catalytic triad. A mutational analysis showed this catalytic triad to be
      essential for the deamidation of UBC13. Our results suggest that S. flexneri
      inhibits acute inflammatory responses in the initial stage of infection by
      targeting the UBC13-TRAF6 complex.

PMID- 22407320
TI  - Identification and characterization of a bacterial hydrosulphide ion channel.
AB  - The hydrosulphide ion (HS(-)) and its undissociated form, hydrogen sulphide
      (H(2)S), which are believed to have been critical to the origin of life on Earth,
      remain important in physiology and cellular signalling. As a major metabolite in
      anaerobic bacterial growth, hydrogen sulphide is a product of both assimilatory
      and dissimilatory sulphate reduction. These pathways can reduce various oxidized
      sulphur compounds including sulphate, sulphite and thiosulphate. The
      dissimilatory sulphate reduction pathway uses this molecule as the terminal
      electron acceptor for anaerobic respiration, in which process it produces excess
      amounts of H(2)S (ref. 4). The reduction of sulphite is a key intermediate step
      in all sulphate reduction pathways. In Clostridium and Salmonella, an inducible
      sulphite reductase is directly linked to the regeneration of NAD(+), which has
      been suggested to have a role in energy production and growth, as well as in the
      detoxification of sulphite. Above a certain concentration threshold, both H(2)S
      and HS(-) inhibit cell growth by binding the metal centres of enzymes and
      cytochrome oxidase, necessitating a release mechanism for the export of this
      toxic metabolite from the cell. Here we report the identification of a
      hydrosulphide ion channel in the pathogen Clostridium difficile through a
      combination of genetic, biochemical and functional approaches. The HS(-) channel
      is a member of the formate/nitrite transport family, in which about 50
      hydrosulphide ion channels form a third subfamily alongside those for formate
      (FocA) and for nitrite (NirC). The hydrosulphide ion channel is permeable to
      formate and nitrite as well as to HS(-) ions. Such polyspecificity can be
      explained by the conserved ion selectivity filter observed in the channel's
      crystal structure. The channel has a low open probability and is tightly
      regulated, to avoid decoupling of the membrane proton gradient.

PMID- 22407321
TI  - MEGF10 and MEGF11 mediate homotypic interactions required for mosaic spacing of
      retinal neurons.
AB  - In many parts of the nervous system, neuronal somata display orderly spatial
      arrangements. In the retina, neurons of numerous individual subtypes form regular
      arrays called mosaics: they are less likely to be near neighbours of the same
      subtype than would occur by chance, resulting in 'exclusion zones' that separate
      them. Mosaic arrangements provide a mechanism to distribute each cell type evenly
      across the retina, ensuring that all parts of the visual field have access to a
      full set of processing elements. Remarkably, mosaics are independent of each
      other: although a neuron of one subtype is unlikely to be adjacent to another of
      the same subtype, there is no restriction on its spatial relationship to
      neighbouring neurons of other subtypes. This independence has led to the
      hypothesis that molecular cues expressed by specific subtypes pattern mosaics by
      mediating homotypic (within-subtype) short-range repulsive interactions. So far,
      however, no molecules have been identified that show such activity, so this
      hypothesis remains untested. Here we demonstrate in mouse that two related
      transmembrane proteins, MEGF10 and MEGF11, have critical roles in the formation
      of mosaics by two retinal interneuron subtypes, starburst amacrine cells and
      horizontal cells. MEGF10 and 11 and their invertebrate relatives Caenorhabditis
      elegans CED-1 and Drosophila Draper have hitherto been studied primarily as
      receptors necessary for engulfment of debris following apoptosis or axonal
      injury. Our results demonstrate that members of this gene family can also serve
      as subtype-specific ligands that pattern neuronal arrays.

PMID- 22407322
TI  - Crystal structure of a concentrative nucleoside transporter from Vibrio cholerae
      at 2.4 A.
AB  - Nucleosides are required for DNA and RNA synthesis, and the nucleoside adenosine
      has a function in a variety of signalling processes. Transport of nucleosides
      across cell membranes provides the major source of nucleosides in many cell types
      and is also responsible for the termination of adenosine signalling. As a result
      of their hydrophilic nature, nucleosides require a specialized class of integral
      membrane proteins, known as nucleoside transporters (NTs), for specific transport
      across cell membranes. In addition to nucleosides, NTs are important determinants
      for the transport of nucleoside-derived drugs across cell membranes. A wide range
      of nucleoside-derived drugs, including anticancer drugs (such as Ara-C and
      gemcitabine) and antiviral drugs (such as zidovudine and ribavirin), have been
      shown to depend, at least in part, on NTs for transport across cell membranes.
      Concentrative nucleoside transporters, members of the solute carrier transporter
      superfamily SLC28, use an ion gradient in the active transport of both
      nucleosides and nucleoside-derived drugs against their chemical gradients. The
      structural basis for selective ion-coupled nucleoside transport by concentrative
      nucleoside transporters is unknown. Here we present the crystal structure of a
      concentrative nucleoside transporter from Vibrio cholerae in complex with uridine
      at 2.4 A. Our functional data show that, like its human orthologues, the
      transporter uses a sodium-ion gradient for nucleoside transport. The structure
      reveals the overall architecture of this class of transporter, unravels the
      molecular determinants for nucleoside and sodium binding, and provides a
      framework for understanding the mechanism of nucleoside and nucleoside drug
      transport across cell membranes.

PMID- 22407323
TI  - Activation of signaling pathways following localized delivery of systemically
      administered neurotrophic factors across the blood-brain barrier using focused
      ultrasound and microbubbles.
AB  - The brain-derived neurotrophic factor (BDNF) has been shown to have broad
      neuroprotective effects in addition to its therapeutic role in neurodegenerative
      disease. In this study, the efficacy of delivering exogenous BDNF to the left
      hippocampus is demonstrated in wild-type mice (n = 7) through the noninvasively
      disrupted blood-brain barrier (BBB) using focused ultrasound (FUS). The BDNF
      bioactivity was found to be preserved following delivery as assessed
      quantitatively by immunohistochemical detection of the pTrkB receptor and
      activated pAkt, pMAPK, and pCREB in the hippocampal neurons. It was therefore
      shown for the first time that systemically administered neurotrophic factors can
      cross the noninvasively disrupted BBB and trigger neuronal downstream signaling
      effects in a highly localized region in the brain. This is the first time that
      the administered molecule is tracked through the BBB and localized in the neuron
      triggering molecular effects. Additional preliminary findings are shown in wild
      type mice with two additional neurotrophic factors such as the glia-derived
      neurotrophic factor (n = 12) and neurturin (n = 2). This further demonstrates the
      impact of FUS for the early treatment of CNS diseases at the cellular and
      molecular level and strengthens its premise for FUS-assisted drug delivery and
      efficacy.

PMID- 22407324
TI  - Expression of metallothioneins in cutaneous squamous cell carcinoma and actinic
      keratosis.
AB  - Metallothioneins (MT) are low-molecular weight proteins implicated in heavy metal
      detoxification, zinc and cooper homeostasis and cell protection against free
      radicals. In variety of cancers MT-overexpression was shown, but there are just a
      few studies on the role of MT in skin carcinogenesis. Current study was
      undertaken to evaluate MT and Ki-67 expression in pre-cancerous skin lesions as
      well as in fully developed skin cancers. 73 squamous cell carcinomas (SCC), 23
      actinic keratoses (AK) and 20 normal skin samples were included in the study. In
      obtained paraffin sections immunohistochemical reactions were performed. MT
      expression in SCC (mean 2.89 +/- 1.83) was significantly higher than in AK (mean
      1.69 +/- 1.26)(p = 0.006) and higher than in normal skin (mean 2 +/- 0.79) (p =
      0.0075). The MT-expression positively correlated with Ki-67 expression (R = 0.28;
      p = 0.017) in SCC and in AK (R = 0.49; p = 0.018). Various clinico-pathological
      variables, e.g. morphology, size of lesions and the depth of neoplastic
      infiltration were not associated to MT-expression in both SCC and AK. The grade
      of histological differentiation of SCC correlated positively with Ki-67 antigen
      (p < 0.001) and did not correlate with MT-expression (p = 0.06). Ki-67 expression
      was higher in SCC and in AK than in healthy skin (p = 0,003). In SCC and in AK
      expression of Ki-67 antigen correlated positively with MT-expression
      (respectively p = 0.017 and p = 0.018). MT may serve as a good markers of
      proliferation in SCC and AK. MT-overexpression in SCC may suggest a potential
      role of MT in skin carcinogenesis.

PMID- 22407325
TI  - Myeloperoxidase production by macrophage and risk of atherosclerosis.
AB  - Myeloperoxidase (MPO), a member of the heme peroxidase superfamily, is a
      leukocyte-derived enzyme that generates reactive intermediates, leading to
      oxidative damage of host lipids and proteins. It has been shown that MPO is
      present within atherosclerotic plaque in human arteries and contributes to
      atherogenesis by catalyzing oxidative reactions in the vascular wall. This review
      provides an overview of the analytical and pathophysiologic characteristics of
      MPO and summarizes the possible clinical applicability of MPO as a marker for
      diagnosis of acute coronary syndrome and a marker for prediction of
      cardiovascular disease.

PMID- 22407326
TI  - Chemical and nutritional composition of tejate, a traditional maize and cacao
      beverage from the Central Valleys of Oaxaca, Mexico.
AB  - Foam-topped cacao and maize beverages have a long history in Mesoamerica. Tejate
      is such a beverage found primarily in the Zapotec region of the Central Valleys
      of Oaxaca, Mexico. Historically tejate has been ceremonially important but also
      as an essential staple, especially during periods of hard fieldwork. However, the
      nutritional contribution of traditional foods such as tejate has not been
      investigated. We analyzed tejate samples from three Central Valley communities,
      vendors in urban Oaxaca markets and one migrant vendor in California, USA for
      their proximate composition, amino acid content and scores, and mineral and
      methylxanthine content. Nutritional and chemical variation exists among tejate
      recipes, however, the beverage is a source of energy, fat, methylxanthines, K, Fe
      and other minerals although their availability due to presence of phytates
      remains to be determined. Tejate is a source of protein comparable to an equal
      serving size of tortillas, with protein quality similarly limited in both. Tejate
      provides the nutritional benefits of maize, and some additional ones, in a form
      appealing during hot periods of intense work, and year round because of its
      cultural significance. Its substitution by sodas and other high glycemic
      beverages may have negative nutritional, health and cultural consequences.

PMID- 22407327
TI  - Mono- and dinuclear nickel(II) complexes of resolved Schiff-base ligands with
      extended quinoline substituents.
AB  - The coordination chemistry of four enantiopure tetradentate bis(iminoquinoline)
      ligands with nickel(II) salts is reported. The previously reported ligands CBQ,
      CPQ, BBQ, and BPQ result from the condensation of (1R,2R)-cyclohexyldiamine or
      (R)-BINAM with two equivalents of 2-formylbenzo[h]quinoline or 8-isopropyl-2
      quinolinecarboxaldehyde {CBQ = (1R,2R)-cyclohexanediamine-N,N'
      bis(benzo[h]quinoline-2-ylmethylene), CPQ = (1R,2R)-cyclohexanediamine-N,N'
      bis[[(8-isopropyl)-2-quinolinyl]methylene], BBQ = [(R)-1,1'-binaphthalene]-2,2'
      diamine-N,N'-bis(benzo[h]quinoline-2-ylmethylene), BPQ = [(R)-1,1'-binaphthalene]
      2,2'-diamine-N,N'-bis[[(8-isopropyl)-2-quinolinyl]methylene]}. Reaction of NiI(2)
      with the (1R,2R)-cyclohexyl ligands gives the mononuclear distorted trigonal
      bipyramidal (TBP) complexes [Ni(N(3)-CBQ)I(2)] and [Ni(N(3)-CPQ)I(2)]. Incomplete
      iodide abstraction from [Ni(N(3)-CPQ)I(2)] with AgOTf leads to partial
      replacement of the iodide with hydroxide from adventitious water to give [Ni(N(3)
      CPQ)I(1.6)(OH)(0.4)] (distorted TBP). The corresponding reaction with [Ni(N(3)
      CBQ)I(2)] again fails to remove all of the iodide, resulting instead in
      conversion to the syn dinuclear [Ni(2)(CBQ)(MU-X)(2)I(2)] (X = Cl(0.925)I(0.075))
      complex, where chloride abstraction from the solvent (CH(2)Cl(2)) has resulted in
      a mixed halide system and the metal centers are square-pyramidal. Reaction of
      Ni(OTf)(2) with CBQ leads to the isolation of the octahedral cation
      [Ni(CMBQ)(2)](2+), with CMBQ [(1R,2R)-cyclohexanediamine-mono-N
      (benzo[h]quinoline-2-ylmethylene)] being the partial hydrolysis product of CBQ.
      [Ni(CMBQ)(2)][OTf](2) crystallizes as a 1:1 mixture of P and M helical
      diastereomers. The coordination of NiI(2) with the (R)-BINAM derived ligands
      yields the anti dinuclear P-helical complexes [Ni(2)(BBQ)(MU-I)(2)I(2)] and
      [Ni(2)(BPQ)(MU-I)(2)I(2)]: one nickel ion is coordinated in each bidentate
      iminoquinoline pocket and the geometry at the metal centers is distorted square
      pyramidal. Characterisation by (1)H NMR, UV-Vis, electronic circular dichroism
      (ECD) spectroscopy, combustion analysis, and HRMS is reported in addition to
      structural and halide abstraction studies.

PMID- 22407328
TI  - Altered expression of farnesyl pyrophosphate synthase in prostate cancer:
      evidence for a role of the mevalonate pathway in disease progression?
AB  - BACKGROUND: Preclinical studies demonstrated effects of drugs inhibiting the
      mevalonate pathway including nitrogen-containing bisphosphonates (N-BPs) and
      statins on tumor growth and progression. The exact role of this pathway in
      prostate cancer (PC) has not been identified yet. Herein, we evaluate the
      expression of farnesyl pyrophosphate synthase (FPPS), the key enzyme of the
      mevalonate pathway, in PC. PATIENTS AND METHODS: Prostate cancer (PC) and benign
      prostate tissue of 114 men who underwent radical prostatectomy were constructed
      to a tissue microarray. Immunohistochemical staining of FPPS was quantified by
      the Remmele/Stegner immunoreactivity-score. Patients' clinical follow-up was
      assessed. IRS was correlated to pathological and clinical data. The impact of
      FPPS expression on clinical course was assessed univariate and multivariate.
      RESULTS: Mean IRS in PC and benign tissue was 5.7 (95% CI 5.0-6.5) and 2.6 (2.1
      3.0, p < 0.0001). Mean IRS in PC tissue of patients with organ-confined and
      locally advanced disease (pT >= 3) was 5.09 (4.22-5.96) and 6.87 (5.57-8.17, p =
      0.035). IRS of PC tissue significantly correlated with Gleason score (p = 0.03).
      Patients with PC tissue IRS >3 showed shorter recurrence-free survival compared
      to the remaining (p = 0.01). Increased FPPS expression is an independent risk
      factor for early biochemical recurrence (p = 0.032). CONCLUSIONS: This is the
      first study on FPPS in PC specimens. The association of FPPS with established
      histopathological risk parameters and biochemical recurrence implicates a
      contribution of the mevalonate pathway to PC progression. Further functional
      analysis is required to explore the role of this pathway in PC and to investigate
      whether FPPS expression affects the response of PC cells to N-BPs.

PMID- 22407329
TI  - Exercise thermoregulatory responses following a 28-day sleep-high train-low
      regimen.
AB  - The potentiated exercise-sweating rate observed during acute hypoxia is
      diminished after a sleep-high train-low (SH-TL) regimen. We tested the hypothesis
      that this attenuation of the sweating response after SH-TL is compensated for by
      an increase in heat loss via vasodilatation. Nine male subjects participated in a
      28-day SH-TL regimen. Before (pre-), and after (post-) the SH-TL protocol, they
      performed an VO2peak test under normoxia and hypoxia. Additionally, pre- and post
      SH-TL they completed three 30-min constant-work rate trials on a cycle ergometer.
      In one trial, the subjects inspired room air while exercising at 50% of normoxic
      VO2peak (CT). In the remaining trials, subjects exercised in hypoxia (F(I)O2
      12.5%), either at the same absolute (HAT) or relative (50% of hypoxic VO2peak
      work rate (HRT) as in CT. Despite similar exercise core temperature responses
      between pre- and post-SH-TL trials, sweating rate was potentiated in HAT pre-SH
      TL [CT: 1.97 (0.42); HRT: 1.86 (0.31); HAT: 2.55 (0.53) mg cm(-2) min(-1); p <
      0.05]. Post-SH-TL exercise sweating rate was increased for CT, and remained
      unchanged in HRT and HAT [CT: 2.42 (0.76); HRT: 2.01 (0.33); HAT: 2.59 (0.30) mg
      cm(-2) min(-1)]. Pre-SH-TL, the forearm-fingertip skin temperature difference
      (Tsk(f-f)) was higher in HAT than in CT and HRT by ~3.5  degrees C (p < 0.05).
      The inter-condition differences in Tsk(f-f) were diminished post-SH-TL. In
      conclusion, the decrease in sweating rate during hypoxic exercise, following a SH
      TL regimen, was countered by an increase in vasodilatation (reduced Tsk(f-f)),
      whereas SH-TL enhanced the sweating response during normoxic exercise. The
      mechanisms underlying these SH-TL-induced alterations in thermoregulatory
      responses remain to be settled.

PMID- 22407330
TI  - Variation of force amplitude and its effects on local fatigue.
AB  - Trends in industry are leaning toward stereotyped jobs with low workloads.
      Physical variation is an intervention to reduce fatigue and potentially
      musculoskeletal disorders in such jobs. Controlled laboratory studies have
      provided some insight into the effectiveness of physical variation, but very few
      have been devoted to force variation without muscular rest as a component. This
      study was undertaken to determine multiple physiological responses to five
      isometric elbow extension protocols with the same mean amplitude (15% maximum
      voluntary contraction, MVC), cycle time (6 s), and duty cycle (50 %). Sustained
      (15 %Sus) and intermittent contractions including zero force (0-30 %Int) differed
      significantly in 19 of 27 response variables. Contractions varying by half the
      mean force (7.5-22.5 %Int) led to 8 and 7 measured responses that were
      significantly different from 0-30 %Int and 15 %Sus, respectively. A sinusoidal
      condition (0-30 %Sine) resulted in 2 variables that were significantly different
      from 0-30 %Int, and 16 different from 15 %Sus. Finally, ten response variables
      suggested that varying forces with 1 % as the lower contraction level was
      significantly less fatiguing than 15 %Sus, while no responses were significantly
      different from 0-30 %Int. Sustained contractions led to decreased twitch force 24
      h post-exercise, whereas recovery was complete within 60 min after intermittent
      contractions. This suggests that time-varying force may be a useful intervention
      to reduce local fatigue in workers performing low-load tasks, and also that rest
      per se did not seem to cause any extraordinary effects beyond those predictable
      from the force variation amplitude.

PMID- 22407331
TI  - Low Plasma Hdl Cholesterol and Elevated C Reactive Protein further Increase
      Cardiovascular Disease Risk in Latinos with Type 2 Diabetes.
AB  - The purpose of this study was to determine whether low plasma HDL and high C
      reactive protein (CRP) concentrations would further increase cardiovascular
      disease (CVD) risk in Latinos with poorly controlled type-2 diabetes, already at
      high risk for CVD. Subjects (n = 68) were grouped into High-HDL (>= or 1.03 or
      1.3 mmol/L) or Low-HDL (<1.03 or 1.3 mmol/L) for men and women, respectively.
      Following classification, risk factors for CVD including apolipoproteins,
      lipoprotein size and subfraction distribution were assesed. Similarly,
      participants were divided according to their CRP levels (>= or < 3mg/L) and key
      inflammatory markers as well as leptin and adiponectin were analyzed. The Low-HDL
      group had higher concentrations of the atherogenic particles, large and medium
      VLDL and the smaller LDL subfractions compared to the High-HDL group (p<0.001).
      Consistently, VLDL diameter was larger and LDL diameter smaller in the Low HDL
      group (p<0.001). The High-CRP group had larger waist circumference (p<0.001) and
      body mass index (p<0.001) than the Low-CRP group. Leptin was also higher in the
      High- CRP group (p< 0.01). These data suggest that Latinos with type-2 diabetes
      having either Low-HDL or High-CRP concentrations are at a higher risk for
      atherosclerosis and CVD than their counterparts who have High-HDL or Low-CRP.

PMID- 22407332
TI  - Expression of estrogen receptor beta1 in colorectal cancer: correlation with
      clinicopathological variables.
AB  - Colorectal cancer (CRC) is a common malignancy in both genders with a high death
      rate, accounting for about 56,000 each year in the USA only. In this study we
      examined the differences in CRC between the genders. We also looked for
      differences in the staining of the tumors and adjacent colonic mucosa to estrogen
      receptor beta1 and its possible prognostic value. Fifty-five specimens from
      patients who underwent resection of colon cancer in our institute were sectioned
      and stained for estrogen receptor beta1. The histopathological slides were
      evaluated for positive staining in the tumor and the normal colonic mucosa as
      well. The results were statistically analyzed. Positive estrogen receptor beta1
      stain was found in the nuclei of the tumor cells. We noted positive stain also in
      the cytoplasm of the tumor cells. Similar findings were observed in the normal
      colonic mucosa. Statistically significant differences were found regarding the
      positivity of the staining between the deceased and surviving patients, men/women
      and those who had metastases vs. the non-metastatic ones. Our data suggest that
      there is an estrogen influence on the development and progression of colon
      cancer. Furthermore, it was found to be higher in the more severe cases.

PMID- 22407333
TI  - 10th Dresdner Sensor-Symposium--an anniversary to celebrate.

PMID- 22407334
TI  - Acoustic deposition with NIMS as a high-throughput enzyme activity assay.
AB  - Mass spectrometry (MS)-based enzyme assay has been shown to be a useful tool for
      screening enzymatic activities from environmental samples. Recently, reported
      approaches for high-specificity multiplexed characterization of enzymatic
      activities allow for providing detailed information on the range of enzymatic
      products and monitoring multiple enzymatic reactions. However, the throughput has
      been limited by the slow liquid-liquid handling and manual analysis. This rapid
      communication demonstrates the integration of acoustic sample deposition with
      nanostructure initiator mass spectrometry (NIMS) imaging to provide reproducible
      measurements of multiple enzymatic reactions at a throughput that is tenfold to
      100-fold faster than conventional MS-based enzyme assay. It also provides a
      simple means for the visualization of multiple reactions and reaction pathways.

PMID- 22407336
TI  - Rotational dynamics of thiocyanate ions in highly concentrated aqueous solutions.
AB  - The thiocyanate (SCN(-)) anion is known as one of the best denaturants, which is
      also capable of breaking the hydrogen-bond network of water and destabilizing
      native structures of proteins. Despite prolonged efforts to understand the
      underlying mechanism of such Hofmeister effects, detailed dynamics of the ions in
      a highly concentrated solution have not been fully elucidated yet. Here, we used
      a dispersive IR pump-probe spectroscopic method to study the dependence of
      vibrational lifetimes and rotational relaxation times of thiocyanate ions on KSCN
      concentration in D(2)O. The nitrile stretch mode is used as a vibrational probe
      for dispersed IR pump-probe and FTIR measurements. To avoid possible self
      attenuation of the IR pump-probe signal by highly concentrated SCN(-) ions, we
      added a small amount of (13)C-isotope-labeled thiocyanate ions (S(13)CN(-)) and
      focused on the excited-state absorption contribution to the IR pump-probe signal
      of the (13)C-isotope-labeled nitrile stretch mode. Quite unexpectedly, the
      vibrational lifetime of S(13)CN(-) ions is independent of the total KSCN
      concentration in the range from 0.46 m (molality) to 11.8 m while the rotational
      relaxation time of S(13)CN(-) ions is linearly dependent on the total KSCN
      concentration. By combining the present experimental findings with the fact that
      the dissolved ions of KSCN salt have a strong tendency to form a large ion
      cluster in a highly concentrated aqueous solution, we believe that the ion
      clusters consisting of potassium and thiocyanate ion pairs in D(2)O behave like
      ionic liquids and the ions inside ion clusters are weakly bound by electrostatic
      Coulombic interactions. The ability of SCN(-) ions to form ion clusters in
      aqueous protein solutions seems to be a key to understand the Hofmeister ion
      effect. We anticipate that the present experimental results provide a clue for
      further elucidating the underlying mechanism of the Hofmeister ion effects on
      protein stability in the future.

PMID- 22407337
TI  - Polyamines detoxify the anticoagulant effect of acetaldehyde on prothrombin time.
AB  - Naturally occurring bioamines, such as putrescine, cadaverine, agmatine,
      spermidine, and spermine, were tested at pharmacological levels for their
      capacity to affect prothrombin time (PT). Each of the bioamines tested prolonged
      PT with decreasing orders of sensitivity being agmatine > spermidine > spermine >
      putrescine > cadaverine. The respective millimolar concentrations, which
      exhibited prolongation in statistically significant concentrations were 1, 3, 3,
      6, and 10 mM, respectively. Acetaldehyde (AcH) prolongs PT. Because amines react
      with AcH to form Schiff bases, the bioamines were tested for their potential to
      affect the prolongation of PT by AcH. It was observed that mixtures of each of
      the bioamines with AcH, upon preincubation at room temperature for 20 minutes
      before addition to plasma for a further 20 minutes (at room temperature),
      generated a major reduction in the prolongation of clotting time relative to that
      of AcH alone, thereby affecting a detoxication of AcH. Sequential addition of AcH
      first and bioamine second to plasma generally lowered prolongation of PT to a
      lesser extent. These results suggest that interaction of AcH, the highly reactive
      primary intermediate in the metabolism of ethanol, with bioamines may affect the
      physiological and pharmacological roles of the bioamines in vivo by diminishing
      the levels of free amines, in addition to affecting a detoxication of
      acetaldehyde.

PMID- 22407338
TI  - Neurogenic and endothelial nitric oxide regulates blood circulation in lingual
      and other oral tissues.
AB  - Blood flow in oral tissues, including the tongue, salivary glands, gingiva,
      dental pulp, and lip, plays an important role in modulating the complex oral
      functions involved in food intake. Oral tissue circulation is regulated by nitric
      oxide (NO) synthesized by neuronal NO synthase mainly present in parasympathetic
      vasodilator neurons and also by endothelial NO sythase. Electrical stimulation of
      parasympathetic nerves causes vasodilatation and blood flow increase in the
      tongue, submandibular gland, and lip in various mammals in vitro and in vivo.
      Lingual arteries isolated from Japanese monkeys respond to perivascular nerve
      stimulation by electrical pulses and nicotine with relaxations that are mediated
      via neurogenic NO. There is evidence supporting the hypothesis that the superior
      salivatory nucleus delivers central information through the geniculate ganglion
      and greater petrosal nerve to the pterygopalatine ganglion, which sends off
      impulses through nitrergic nerves to oral tissues. Endothelial NO also plays an
      important role in improving oral blood circulation not only in resting conditions
      but also under conditions activated by chemical and physical stimuli in the
      tongue, submandibular and parotid glands, dental pulp/gingiva, and cheek pouch.
      Maintenance of health in oral circulation by minimizing factors responsible for
      impairment of endothelial and neurogenic NO bioavailability would be important
      for the prophylaxis of life-style related diseases.

PMID- 22407339
TI  - Effect of a physical activity intervention on the metabolic syndrome in Pakistani
      immigrant men: a randomized controlled trial.
AB  - Physical activity (PA) is thought to prevent the metabolic syndrome (MetS), which
      is prevalent among south Asian immigrants in Western countries. The purpose of
      this study was to explore whether increasing PA improves the MetS and associated
      components in a group of Pakistani immigrant men living in Norway. One- hundred
      and fifty physically inactive Pakistani immigrant men were randomized to either a
      control group (CG) or an intervention group (IG). The 5 months intervention
      focused on increasing PA level, which was assessed using accelerometer
      recordings. Total PA level (counts min(-1)) increased significantly more in the
      IG than in the CG. The mean difference between the two groups was 49 counts min(
      1), which translates into a 15% (95% CI = 8.7% to 21.2%; P = 0.01) greater
      increase in total PA level in the IG than in the CG. Serum insulin concentration
      and waist circumference decreased more in the IG compared with the CG. Other MetS
      related factors and the prevalence of the MetS did not differ between the groups
      after the intervention. A five- month intervention program can increase PA level
      and cardiorespiratory fitness, and reduce insulin concentration and waist
      circumference. However this intervention program may not lower the prevalence of
      the complete MetS in Pakistani immigrant men.

PMID- 22407340
TI  - Silencing of skeletal metastasis-associated genes impairs migration of breast
      cancer cells and reduces osteolytic bone lesions.
AB  - Bone sialoprotein (BSP) and osteopontin (OPN) are important factors in the
      metastasis of breast cancer, which were examined as targets for antineoplastic
      therapy by siRNA. In addition, the effect of gene silencing on their
      transcription factor Runx2 and their interaction partners integrin beta(3) and
      matrix metalloproteinase 2 was studied. The effect of siRNAs directed against
      these genes was assessed by monitoring expression levels followed by functional
      assays in cell culture as well as skeletal metastases caused by human MDA-MB
      231(luc) breast cancer cells in nude rats. Upon silencing of the targets, cell
      migration was profoundly impaired (p < 0.001 for BSP-siRNA), but the impact on
      proliferation was low. Systemic administration by osmotic mini-pumps of BSP-siRNA
      but not OPN-siRNA decreased osteolytic lesions (p = 0.067). Extraosseous tumour
      growth was not affected. As an alternative approach, non-viral, polymeric based
      formulations of siRNAs in nanoparticles (NP) were developed. Locoregional
      administration of the two siRNAs targeting OPN and BSP encapsulated in these
      biodegradable NP reduced skeletal lesions even more efficiently (p = 0.03).
      Compared to systemic administration, this treatment caused not only a more
      pronounced anti-osteolytic effect at a 25-fold lower total siRNA dose, but also
      had a slight reducing effect on tumour incidence (p = 0.095). In conclusion, the
      siRNA treatment had a small effect on cellular proliferation but a significant
      efficacy against migration of and osteolysis induced by MDA-MB-231 cells. Our
      data underline that siRNA mediated knockdown is a powerful tool for identifying
      targets for pharmacological intervention. In addition, encapsulation of siRNA
      into biodegradable NP is a strategy, which promises well for using siRNA.

PMID- 22407342
TI  - Development and validation of stability-indicating HPLC and UPLC methods for the
      determination of bicalutamide.
AB  - Six new process related impurities (Imp-08, Imp-09, Imp-10, Imp-12, Imp-13 and
      Imp-14) of bicalutamide (BCT) have been reported in this paper. BCT was subjected
      to oxidative, acid, alkaline, hydrolytic, thermal and photolytic degradation
      conditions and found to degrade in alkaline condition, yielding Imp-11. Stability
      indicating high-performance liquid chromatography and ultra-performance liquid
      chromatography methods were developed for the determination of BCT in the
      presence of its 14 process-related impurities and 1 degradant by using Zorbax SB
      phenyl column (150 * 4.6 mm * 3.5 um) and HSS T3 column (100 * 2.1 mm * 1.8 um),
      respectively. Both the methods were validated as per International Conference on
      Harmonization guidelines. Quantitation limits (QL) were found be in the ranges of
      0.02-0.03% for both the methods. Precision was evaluated by replicate analysis in
      which % relative standard deviation (RSD) values for areas were found below 2.0.
      Linearity for the impurities was established in the range of QL to 200% of the
      specification level and the correlation coefficients derived from of the
      respective calibration curves were approximately 0.999. The recoveries obtained
      for purity (90-100%) and assay (98-102%) ensured the accuracy of the developed
      methods.

PMID- 22407343
TI  - Chemometrically assisted development and validation of LC-UV and LC-MS methods
      for simultaneous determination of torasemide and its impurities.
AB  - Complete evaluation of chromatographic behavior and establishment of optimal
      experimental conditions for determination of torasemide and its four impurities
      are determined by experimental design. Fractional factorial and 3(n) full
      factorial design were employed for efficient and rapid optimization of liquid
      chromatography-ultraviolet and liquid chromatography-mass spectrometry (LC-MS)
      methods. Separation is achieved on a Zorbax SB C(18) analytical column (250 x 4.6
      mm, 5 um) with mobile phase consisting of acetonitrile and 10 mM ammonium formate
      (pH 2.5 with formic acid) in gradient mode. The flow rate is 1 mL min(-1), the
      temperature of the column is 25  degrees C and UV detection is performed at 290
      nm. The efficiency of ionization in electrospray ionization is higher than in
      atmospheric pressure chemical ionization mode; therefore, it is further used for
      analysis of torasemide and its impurities. Both methods meet all validation
      criteria. The calibration curves show high linearity with the coefficients of
      correlation (r) greater than 0.9982. The obtained recovery values (95.78-104.92%)
      and relative standard deviation values (0.12-5.56%) indicate good accuracy and
      precision. Lower limit of detection (LOD) and limit of quantitation (LOQ) values
      are obtained with the LC-MS method, indicating higher sensitivity of the proposed
      method.

PMID- 22407344
TI  - HPLC separation of acetaminophen and its impurities using a mixed-mode reversed
      phase/cation exchange stationary phase.
AB  - Determination of acetaminophen and its main impurities: 4-nitrophenol, 4'
      chloroacetanilide, as well as 4-aminophenol and its degradation products, p
      benzoquinone and hydroquinone has been developed and validated by a new high
      performance liquid chromatography method. Chromatographic separation has been
      obtained on a Hypersil Duet C18/SCX column, using gradient elution, with a
      mixture of phosphate buffer (pH = 4.88) and methanol as a mobile phase. Analysis
      time did not exceed 14.5 min and good resolutions, peak shapes and asymmetries
      have resulted. The linearity of the method has been tested in the range of 5.0-60
      ug/mL for acetaminophen and 0.5-6 ug/mL for the other compounds. The limits of
      detection and quantification have been also established to be lower than 0.1
      ug/mL and 0.5 ug/mL, respectively. The method has been successfully applied for
      the analysis of commercial acetaminophen preparations.

PMID- 22407345
TI  - Method development and validation for the determination of indiquinoline
      tartrate, a novel kappa opioid agonist, and its related substances by high
      performance liquid chromatography.
AB  - A stability-indicating reversed-phase high-performance liquid chromatography
      method has been developed and validated for the assay of indiquinoline tartrate
      and its related substances. The method was established by forced degradation
      experiments and system suitability experiments. The chromatographic separation
      was achieved with a Hedera ODS-3 column (5 um, 250 mm * 4.6 mm) and the mobile
      phase was constituted (flow rate 1.0 mL/min) of eluant A, aqueous acetate buffer
      and eluant B, CH(3)OH using a gradient elution. A photodiode array detector set
      at 254 nm was used for detection. The investigated validation elements showed
      that the method has acceptable specificity, accuracy, linearity, precision,
      robustness and high sensitivity with limit of detection and limit of
      quantitation. The method can be used for routine quality control analysis and
      stability testing of indiquinoline tartrate drug substance.

PMID- 22407346
TI  - Qualification and quantification of seventeen natural steroids in plasma by GC-Q
      MS and GC-IT-MS/MS.
AB  - Studying the plasma steroid profile offers information about the possible
      existence of endocrinological alterations. This study describes the development
      and validation of gas chromatographic-mass spectrometric and gas tandem mass
      spectrometric methods for the simultaneous identification of 17 steroid hormones
      in human plasma using five different solvents. The n-hexane/ethyl acetate solvent
      mixture, in a proportion of 70/30 (v/v) provided the best results. The extracts
      were derivatized with N-methyl-N-trimethylsilyl-trifluoroacetamide. The obtained
      limits of detection were below 1 ng/mL in the majority of the studied steroids
      and the limits of quantification were below 5 ng/mL; the method obtained good
      linearity, reproducibility, repeatability, accuracy and recoveries above 95% in
      most cases.

PMID- 22407347
TI  - Separation and identification of volatile compounds from liquid cultures of
      Trichoderma harzianum by GC-MS using three different capillary columns.
AB  - A simple, fast, repeatable and less laborious sample preparation protocol was
      developed and applied for the analysis of biocontrol fungus Trichoderma harzianum
      strain FA1132 by using gas chromatography-mass spectrometry. The match factors
      for sample spectra with respect to the mass spectra library of fungal volatile
      compounds were determined and used to study the complex hydrocarbons and other
      volatile compounds, which were separated by using different capillary columns
      with nonpolar, medium polar and high polar stationary phases. To date, more than
      278 volatile compounds (with spectral match factor at least 90%) such as normal
      saturated hydrocarbons (C7-C30), cyclohexane, cyclopentane, fatty acids,
      alcohols, esters, sulfur-containing compounds, simple pyrane and benzene
      derivatives have been identified. Most of these compounds have not previously
      been reported. The method described in this paper is a more convenient research
      tool for the detection of volatile compounds from the cultures of T. harzianum.

PMID- 22407348
TI  - A stability-indicating ultra-performance liquid chromatographic method for
      estimation of related substances and degradants in paliperidone active
      pharmaceutical ingredient and its pharmaceutical dosage forms.
AB  - A simple, linear gradient, rapid, precise and stability-indicating analytical
      method was developed for the estimation of related substances and degradants of
      paliperidone API and tablets. The chromatographic separations were achieved using
      an Acquity ultra-performance liquid chromatograph (BEH 100 mm, 2.1 mm, 1.7 um C
      18 column) employing 0.01 M potassium dihydrogen phosphate buffer (pH 2.0) as
      mobile phase A and acetonitrile-water (9:1) as mobile phase B. A linear gradient
      (mobile phase A, mobile phase B in the ratio of 84:16) with a 0.45 mL/min flow
      rate was chosen. All six impurities were eluted within five minutes of run time.
      The column temperature was maintained at 25  degrees C and a detector wavelength
      of 238 nm was employed. Paliperidone was exposed to thermal, photolytic,
      hydrolytic and oxidative stress conditions. The stressed samples were analyzed by
      the proposed method. Considerable degradation of the analyte was observed when it
      was subjected to oxidative conditions and impurity F was found to be the major
      degradant. Peak homogeneity data of paliperidone obtained by photodiode array
      (PDA) detection demonstrated the specificity of the method in the presence of
      degradants. The method was validated with respect to linearity, precision,
      accuracy, ruggedness, robustness, limit of detection and limit of quantification.

PMID- 22407349
TI  - Na+/H+-exchanger-1 inhibition counteracts diabetic cataract formation and retinal
      oxidative-nitrative stress and apoptosis.
AB  - The Na+-H+-exchanger-1 (NHE-1) controls intracellular pH and glycolytic enzyme
      activities, and its expression and activity are increased by diabetes and high
      glucose. NHE-1-dependent upregulation of the upper part of glycolysis, under
      conditions of inhibition (lens) or insufficient activation (retina) of
      glyceraldehyde 3-phosphate dehydrogenase, underlies diversion of the excessive
      glycolytic flux towards several pathways contributing to oxidative stress, a
      causative factor in diabetic cataractogenesis and retinopathy. This study
      evaluated the role for NHE-1 in diabetic cataract formation and retinal oxidative
      stress and apoptosis. Control and streptozotocin-diabetic rats were maintained
      with or without treatment with the NHE-1 inhibitor cariporide (Sanofi-Aventis, 10
      mgkg-1d-1) for 3.5 months. In in vitro studies, bovine retinal pericytes and
      endothelial cells were cultured in 5 or 30 mM glucose, with or without 10 uM
      cariporide, for 7 days. A several-fold increase of the by-product of glycolysis,
      alpha-glycerophosphate, indicative of activation of the upper part of glycolysis,
      was present in both rat lens and retina at an early (1-month) stage of
      streptozotocin-diabetes. Cariporide did not affect diabetic hyperglycemia and
      counteracted lens oxidative-nitrative stress and p38 MAPK activation, without
      affecting glucose or sorbitol pathway intermediate accumulation. Cataract
      formation (indirect ophthalmoscopy and slit-lamp examination) was delayed, but
      not prevented. The number of TUNEL-positive cells per flat-mounted retina was
      increased 4.4-fold in diabetic rats (101 +/- 17 vs. 23 +/- 8 in controls ,
      P<0.01), and this increase was attenuated by cariporide (45 +/- 12, P<0.01).
      Nitrotyrosine and poly(ADP-ribose) fluorescence and percentage of TUNEL-positive
      cells were increased in pericytes and endothelial cells cultured in 30 mM
      glucose, and these changes were at least partially prevented by cariporide. In
      conclusion, NHE-1 contributes to diabetic cataract formation, and retinal
      oxidative-nitrative stress and apoptosis. The findings identify a new therapeutic
      target for diabetic ocular complications.

PMID- 22407350
TI  - Thymic papillo-tubular adenocarcinoma containing a cyst: report of a case.
AB  - We report a case of thymic papillo-tubular adenocarcinoma in a 55-year-old man,
      who had no symptoms. Sternotomy revealed a tumor in the anterior mediastinum,
      tightly adhered to the pericardium. It was resected completely. Interestingly,
      the tumor contained a unilocular cyst filled with mucinous fluid, suggesting that
      it originated from a pre-existing thymic cyst. Pathological examination of the
      tumor revealed a primary thymic papillo-tubular adenocarcinoma resembling a tumor
      of gut origin. Thymic adenocarcinomas, particularly of the tubular subtype, are
      extremely rare.

PMID- 22407351
TI  - Wheat grain yield on saline soils is improved by an ancestral Na+ transporter
      gene.
AB  - The ability of wheat to maintain a low sodium concentration ([Na(+)]) in leaves
      correlates with improved growth under saline conditions. This trait, termed Na(+)
      exclusion, contributes to the greater salt tolerance of bread wheat relative to
      durum wheat. To improve the salt tolerance of durum wheat, we explored natural
      diversity in shoot Na(+) exclusion within ancestral wheat germplasm. Previously,
      we showed that crossing of Nax2, a gene locus in the wheat relative Triticum
      monococcum into a commercial durum wheat (Triticum turgidum ssp. durum var.
      Tamaroi) reduced its leaf [Na(+)] (ref. 5). Here we show that a gene in the Nax2
      locus, TmHKT1;5-A, encodes a Na(+)-selective transporter located on the plasma
      membrane of root cells surrounding xylem vessels, which is therefore ideally
      localized to withdraw Na(+) from the xylem and reduce transport of Na(+) to
      leaves. Field trials on saline soils demonstrate that the presence of TmHKT1;5-A
      significantly reduces leaf [Na(+)] and increases durum wheat grain yield by 25%
      compared to near-isogenic lines without the Nax2 locus.

PMID- 22407352
TI  - A randomized trial of genetic information for personalized nutrition.
AB  - Personal genetic information has become increasingly accessible to the public as
      a result of direct-to-consumer (DTC) genetic tests; however, concerns have been
      raised over their value and potential risks. We compared the effects of providing
      genotype-based dietary advice with general recommendations on behavioral outcomes
      using a randomized controlled study. Participants were men and women from the
      Toronto Nutrigenomics and Health Study between the ages of 20-35 years (n = 149)
      who completed a survey to assess their awareness of DTC genetic tests and
      nutrigenomics, as well as potential motivations for undergoing genetic testing.
      Participants were then randomized into an intervention (I) or control (C) group
      and were given either genotype-based personalized dietary advice or general
      dietary advice, respectively. A second survey was administered to assess the
      participants' opinions of the dietary reports they received. A greater proportion
      of participants in the intervention group agreed that they understood the dietary
      advice they were given (93% (I) vs. 78% (C); p = 0.009). Participants in the
      intervention group were more likely to agree that the dietary recommendations
      they received would be useful when considering their diet (88% (I) vs. 72% (C); p
      = 0.02) and wanted to know more about the recommendations (95% (I) vs. 76% (C); p
      < 0.0001). Only 9% of participants in the intervention group reported feeling
      uneasy about learning their genetic information. These findings suggest that
      individuals find dietary recommendations based on genetics more understandable
      and more useful than general dietary advice. Very few feel uneasy about receiving
      their genetic information that relates to personalized nutrition.

PMID- 22407353
TI  - Targeting focal adhesion assembly by ethoxyfagaronine prevents lymphoblastic cell
      adhesion to fibronectin.
AB  - BACKGROUND: Leukemic cell adhesion to proteins of the bone marrow
      microenvironment provides signals which control morphology, motility and cell
      survival. We described herein the ability of ethoxyfagaronine (etxfag), a soluble
      synthetic derivative of fagaronine, to prevent leukemic cell adhesion to
      fibronectin peptide (FN/V). METHODS: Phosphorylation of fak and pyk2 were
      evaluated by immunoblotting. Labelled proteins were localized by confocal
      microscopy. PI 3-kinase activity was evaluated by in vitro kinase assay. RESULTS:
      Subtoxic concentration of etxfag reduced L1210 cell adhesion to FN/V dependently
      of beta1 integrin engagement. Etxfag impaired FN-dependent formation of beta1
      clustering without modifying beta1 expression at the cell membrane. This was
      accompanied by a decrease of focal adhesion number, a diminution of fak and pyk2
      phosphorylation at Tyr-576, Tyr-861 and Tyr-579, respectively leading to their
      dissociations from beta1 integrin and inhibition of PI 3-kinase activity. Etxfag
      also induced a cell retraction accompanied by a redistribution of phosphorylated
      fak and pyk2 in the perinuclear region and lipid raft relocalization. CONCLUSION:
      Through its anti-adhesive potential, etxfag, combined with conventional cytotoxic
      drugs could be potentially designed as a new anti-leukemic drug.

PMID- 22407354
TI  - Is heart rate a treatment target in heart failure?
AB  - Clinical and experimental studies confirmed an association between elevated
      resting heart rate and the risk of mortality in heart failure patients.
      Importantly, elevated heart rate at rest has been identified as a key finding in
      heart failure addressing a major treatment target. This review shows that heart
      rate level at rest and its extent of reduction is a sensitive indicator for
      successful therapy in heart failure patients demonstrating the specific influence
      of heart rate reduction on clinical outcome in the analyzed patients. Currently,
      experimental data provide convincing evidence of a pathophysiological concept of
      heart rate reduction; nevertheless, transition from experimental results to
      clinical evidence needs further clarification, especially in patients with
      diastolic heart failure. Since heart rate can be easily determined during
      physical examination, decrease in heart rate of patients allows a simple hint on
      prognosis and efficiency of heart failure therapy.

PMID- 22407355
TI  - Long-term results of primary and secondary resections in patients with
      retroperitoneal soft tissue sarcoma.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to analyse treatment and
      long-term outcome for primary and recurrent disease in patients with
      retroperitoneal soft tissue sarcoma (RSTS). METHODS: Clinicopathological data
      including tumour stage, grade, and histological subtype, location of the
      principal tumour, completeness of resection and operative procedure were studied.
      Kaplan-Meier estimations and Cox regression analyses were performed. RESULTS:
      Patients comprised a primary resection group (PRG, n = 42), and a secondary
      resection group (SRG, n = 12) which included patients with recurrent RSTS and/or
      metastatic RSTS. Postoperative complications occurred in 15 patients (PRG: n = 13
      (31%); SRG: n = 2, (16.7%)) and overall 30-day mortality was 5.6% (PRG: n = 2
      (4.8%); SRG: n = 1 (8.3%)). Median overall survival was 58 months (PRG 60 months,
      SRG 50 months) with a 5-year survival rate of 39% (PRG 35.7%, SRG 50%) and a 1
      year survival of 74.1% (PRG 71.4%, SRG 83.3%). Multivariate Cox regression
      analyses indicated that histopathological subtype (P = 0.006), completeness of
      resection (P < 0.001) and tumour grade (P = 0.018) were independent prognostic
      variables for overall survival. CONCLUSION: In the absence of effective
      alternative treatment options, patients with RSTS should undergo extended
      resection, even in recurrent disease. Complete surgical resection is still the
      most effective modality for the treatment of retroperitoneal sarcoma.

PMID- 22407356
TI  - Cross-cultural development of an EORTC questionnaire to assess health-related
      quality of life in patients with testicular cancer: the EORTC QLQ-TC26.
AB  - OBJECTIVE: Testicular cancer (TC) is the most common cancer in young men, and its
      incidence is increasing. The low mortality rate makes quality of life (QOL) an
      important issue in this patient group. This study aimed to develop a
      supplementary module of the EORTC QLQ-C30 questionnaire to assess TC-specific
      aspects of QOL. METHODS: Questionnaire development was conducted according to
      guidelines from the EORTC Quality of Life Group. Phase I comprised generation of
      QOL issues relevant to TC patients through a literature search and interviews
      with patients and experts. Phase II included operationalization and assessment of
      item relevance. In phase III, items were pre-tested in a cross-cultural sample to
      assess issues such as understandability and intrusiveness of items. RESULTS: In
      phase I and II, an initial list of 69 QOL issues possibly relevant to TC patients
      was refined through patient and expert interviews. The remaining 37 issues were
      operationalized into items and assessed for relevance and priority in an expert
      sample (n = 28) and a patient sample (n = 62) from Austria, Canada and the
      Netherlands. After revision of the item list, 26 items were considered eligible
      for pre-testing in phase III, in which 156 patients from Australia, Austria,
      Italy and Spain participated. All items passed criteria for pre-testing, thus
      forming the new EORTC QLQ-TC26. CONCLUSION: The newly developed EORTC QLQ-TC26 is
      now available in several languages to assess QOL in TC patients receiving
      treatment and in TC survivors. Phase IV of questionnaire development will
      comprise international field testing, including extensive analysis of
      psychometric characteristics of the EORTC QLQ-TC26.

PMID- 22407357
TI  - Divergent strategies for adaptation to desiccation stress in two Drosophila
      species of immigrans group.
AB  - Water balance mechanisms have been investigated in desert Drosophila species of
      the subgenus Drosophila from North America, but changes in mesic species of
      subgenus Drosophila from other continents have received lesser attention. We
      found divergent strategies for coping with desiccation stress in two species of
      immigrans group--D. immigrans and D. nasuta. In contrast to clinal variation for
      body melanization in D. immigrans, cuticular lipid mass showed a positive cline
      in D. nasuta across a latitudinal transect (10 degrees 46'-31 degrees 43'N).
      Based on isofemale lines variability, body melanization showed positive
      correlation with desiccation resistance in D. immigrans but not in D. nasuta. The
      use of organic solvents has supported water proofing role of cuticular lipids in
      D. nasuta but not in D. immigrans. A comparative analysis of water budget of
      these two species showed that higher water content, reduced rate of water loss
      and greater dehydration tolerance confer higher desiccation resistance in D.
      immigrans while the reduced rate of water loss is the only possible mechanism to
      enhance desiccation tolerance in D. nasuta. We found that carbohydrates act as
      metabolic fuel during desiccation stress in both the species, whereas their rates
      of utilization differ significantly between these two species. Further,
      acclimation to dehydration stress improved desiccation resistance due to increase
      in the level of carbohydrates in D. immigrans but not in D. nasuta. Thus,
      populations of D. immigrans and D. nasuta have evolved different water balance
      mechanisms under shared environmental conditions. Multiple measures of
      desiccation resistance in D. immigrans but reduction in water loss in D. nasuta
      are consistent with their different levels of adaptive responses to wet and dry
      conditions on the Indian subcontinent.

PMID- 22407358
TI  - Molecular drug design, synthesis and structure elucidation of a new specific
      target peptide based metallo drug for cancer chemotherapy as topoisomerase I
      inhibitor.
AB  - To evaluate the biological preference of metallopeptide drugs in cancer cells, a
      new dinuclear copper(II) complex [Cu(2)(glygly)(2)(ppz)(H(2)O)(4)].2H(2)O (1)
      (glygly = glycyl glycine anion and ppz = piperazine), was designed and
      synthesized as topoisomerase I inhibitor. The structural elucidation of the
      complex was done by elemental analysis, spectroscopic methods and single crystal
      X-ray diffraction. The in vitro DNA binding studies of complex 1 with CT DNA were
      carried out by employing different optical methods viz. UV-vis, fluorescence and
      circular dichroism. The molecular docking technique was also utilized to
      ascertain the mechanism and mode of action towards the molecular target DNA and
      enzymes. Complex 1 cleaves pBR322 DNA via an oxidative mechanism and strongly
      binds to the DNA minor groove. Furthermore, complex 1 exhibits significant
      inhibitory effects on the catalytic activity of topoisomerase I at a very low
      concentration, ~12.5 MUM, in addition to its excellent SOD mimics (IC(50)~0.086
      MUM).

PMID- 22407359
TI  - Real-time bioluminescence and tomographic imaging of gastric cancer in a novel
      orthotopic mouse model.
AB  - Gastric cancer is the second leading cause of cancer mortality worldwide.
      Understanding the multistep process of carcinogenesis of gastric cancer is
      pivotal to develop novel therapeutic strategies. Molecular imaging in preclinical
      cancer models bridges the gap of laboratory-based experiment and clinical
      translation. To this end, the human gastric cancer cell line SGC-7901 was
      established to stably express luciferase and GFP by lentiviral transduction
      (SGC7901-Luc-GFP). Preclinical models were developed by orthotopic
      transplantation of SGC-7901-Luc-GFP into the sub-serosal layer of the stomach of
      immunocompromised mice. Tumor progression and therapeutic responses were
      dynamically tracked by bioluminescence imaging (BLI). Bioluminescence tomography
      (BLT) was used to monitor stereoscopic morphological and signal changes during
      tumor progression. Good correlation between cell number and bio
      luminescence/fluorescence intensity was observed (R(2)=0.9983/r(2)=0.9974) in
      vitro. Tumor progression and therapeutic response could be successfully followed
      directly by BLI. Importantly, BLT provided a more accurate spatial location and
      tomographic quantification of the internal lesion. In conclusion, our novel
      bioluminescence-based preclinical gastric cancer models enable superior,
      noninvasive monitoring gastric cancer progression and their drug responses. The
      BLT technique in particular, may have great potential for future oncological
      studies.

PMID- 22407361
TI  - One-step synthesis of three-dimensional Pd polyhedron networks with enhanced
      electrocatalytic performance.
AB  - Three-dimensional Pd polyhedron networks (Pd PNs) have been fabricated for the
      first time through a one-step, Cu(2+)-assisted, solution-chemical approach. These
      as-prepared 3D Pd PNs exhibit high stability and remarkably improved
      electrocatalytic activity toward formic acid oxidation over commercially
      available Pd black.

PMID- 22407360
TI  - Downregulation of the creatine transporter SLC6A8 by JAK2.
AB  - Janus-activated kinase-2 (JAK2) participates in the regulation of the Na+-coupled
      glucose transporter SGLT1 and the Na+-coupled amino acid transporter SLC6A19.
      Concentrative cellular creatine uptake is similarly accomplished by Na+-coupled
      transport. The carrier involved is SLC6A8 (CreaT). The present study thus
      explored whether JAK2 regulates the activity of SLC6A8. To this end, cRNA
      encoding SLC6A8 was injected into Xenopus oocytes with or without cRNA encoding
      wild-type JAK2, constitutively active (V617F)JAK2 or inactive (K882E)JAK2.
      Electrogenic creatine transport was determined in those oocytes by dual-electrode
      voltage-clamp experiments. In oocytes injected with cRNA encoding SLC6A8 but not
      in oocytes injected with water or with cRNA encoding JAK2 alone, addition of 1 mM
      creatine to the extracellular bath generated an inward current (I (crea)). In
      SLC6A8 expressing oocytes I (crea) was significantly decreased by coexpression of
      JAK2 or (V617F)JAK2 but not by coexpression of (K882E)JAK2. According to kinetic
      analysis, coexpression of JAK2 decreased the maximal transport rate without
      significantly modifying the affinity of the carrier. In oocytes expressing SLC6A8
      and (V617F)JAK2 I (crea) was gradually increased by the JAK2 inhibitor AG490 (40
      MUM). In SLC6A8 and JAK2 coexpressing oocytes the decline of I (crea) following
      disruption of carrier insertion with brefeldin A (5 MUM) was similar in the
      absence and presence of JAK2. In conclusion, JAK2 is a novel regulator of the
      creatine transporter SLC6A8, which downregulates the carrier, presumably by
      interference with carrier protein insertion into the cell membrane.

PMID- 22407362
TI  - Mutual humanization: a visual exploration of relationships in medical care.
AB  - In this article, I explore the work of the artist Robert Pope (b.1957- d.1992)
      who published a series of paintings and drawings which documented his decade-long
      experience with Hodgkin's lymphoma. More widely, Pope was interested in 'the
      culture' of cancer within hospitals and the relationships embedded in experiences
      of illness and care. Pope published a book that contains much of this work-
      Illness and Healing: Images of Cancer (1991). Many of the original artworks have
      been toured throughout Canada and the United Kingdom at cancer centres and
      medical schools. Using a visual methodology, I present three of Pope's images to
      examine and understand the experiences of patients within acute care settings. I
      conclude that Pope's work can be efficacious in exploring relationships in acute
      care settings.

PMID- 22407363
TI  - Oxidation of a two-dimensional hexagonal boron nitride monolayer: a first
      principles study.
AB  - Two-dimensional (2D) hexagonal boron-nitride oxide (h-BNO) is a structural
      analogue of graphene oxide. Motivated by recent experimental studies of graphene
      oxide, we have investigated the chemical oxidation of 2D h-BN sheet and the
      associated electronic properties of h-BNO. Particular emphasis has been placed on
      the most favorable site(s) for chemisorption of atomic oxygen, and on the
      migration barrier for an oxygen atom hopping to the top, bridge, or hollow site
      on the h-BN surface, as well as the most likely pathway for the dissociation of
      an oxygen molecule on the h-BN surface. We find that when an oxygen atom migrates
      on the h-BN surface, it is most likely to be over an N atom, but confined by
      three neighbor B atoms (forming a triangle ring). In general, chemisorption of an
      oxygen atom will stretch the B-N bond, and under certain conditions may even
      break the B-N bond. Depending on the initial location of the first chemisorbed O
      atom, subsequent oxidation tends to form an O domain or O chain on the h-BN
      sheet. The latter may lead to a synthetic strategy for the unzipping of the h-BN
      sheet along a zigzag direction. A better understanding of the oxidation of h-BN
      sheet has important implications for tailoring the properties of the h-BN sheet
      for applications.

PMID- 22407364
TI  - RAC1 activation mediates Twist1-induced cancer cell migration.
AB  - Epithelial-mesenchymal transition (EMT), which is characterized by the
      suppression of the adhesion protein E-cadherin, is a crucial process that
      promotes metastasis and stem-like properties of cancer cells. However, the
      dissociation of cellular aggregates is not sufficient to explain why cancer cells
      move, and the motile nature of cancer cells undergoing EMT remains elusive. Here,
      we identify a mechanism in which the EMT inducer Twist1 elicits cancer cell
      movement through activation of RAC1. Twist1 cooperates with BMI1 to suppress let
      7i expression, which results in upregulation of NEDD9 and DOCK3, leading to RAC1
      activation and enabling mesenchymal-mode movement in three-dimensional
      environments. Moreover, the suppression of let-7i contributes to Twist1-induced
      stem-like properties. Clinically, activation of the Twist1-let-7i-NEDD9 axis in
      head and neck cancer patients correlates with tumour invasiveness and worse
      outcome. Our results uncover an essential mechanism to explain how Twist1 induces
      the motile stem-like cancer cell phenotype beyond simply suppressing E-cadherin.

PMID- 22407365
TI  - Direct sensing of systemic and nutritional signals by haematopoietic progenitors
      in Drosophila.
AB  - The Drosophila lymph gland is a haematopoietic organ in which progenitor cells,
      which are most akin to the common myeloid progenitor in mammals, proliferate and
      differentiate into three types of mature cell--plasmatocytes, crystal cells and
      lamellocytes--the functions of which are reminiscent of mammalian myeloid cells.
      During the first and early second instars of larval development, the lymph gland
      contains only progenitors, whereas in the third instar, a medial region of the
      primary lobe of the lymph gland called the medullary zone contains these
      progenitors, and maturing blood cells are found juxtaposed in a peripheral region
      designated the cortical zone. A third group of cells referred to as the posterior
      signalling centre functions as a haematopoietic niche. Similarly to mammalian
      myeloid cells, Drosophila blood cells respond to multiple stresses including
      hypoxia, infection and oxidative stress. However, how systemic signals are sensed
      by myeloid progenitors to regulate cell-fate determination has not been well
      described. Here, we show that the haematopoietic progenitors of Drosophila are
      direct targets of systemic (insulin) and nutritional (essential amino acid)
      signals, and that these systemic signals maintain the progenitors by promoting
      Wingless (WNT in mammals) signalling. We expect that this study will promote
      investigation of such possible direct signal sensing mechanisms by mammalian
      myeloid progenitors.

PMID- 22407367
TI  - Critical Care Nursing Quarterly. Foreword.

PMID- 22407366
TI  - Whacked and Rab35 polarize dynein-motor-complex-dependent seamless tube growth.
AB  - Seamless tubes form intracellularly without cell-cell or autocellular junctions.
      Such tubes have been described across phyla, but remain mysterious despite their
      simple architecture. In Drosophila, seamless tubes are found within tracheal
      terminal cells, which have dozens of branched protrusions extending hundreds of
      micrometres. We find that mutations in multiple components of the dynein motor
      complex block seamless tube growth, raising the possibility that the lumenal
      membrane forms through minus-end-directed transport of apical membrane components
      along microtubules. Growth of seamless tubes is polarized along the proximodistal
      axis by Rab35 and its apical membrane-localized GAP, Whacked. Strikingly, loss of
      whacked (or constitutive activation of Rab35) leads to tube overgrowth at
      terminal cell branch tips, whereas overexpression of Whacked (or dominant
      negative Rab35) causes formation of ectopic tubes surrounding the terminal cell
      nucleus. Thus, vesicle trafficking has key roles in making and shaping seamless
      tubes.

PMID- 22407368
TI  - Diffuse alveolar hemorrhage-induced respiratory failure.
AB  - This case study discusses the management of type I respiratory failure (RF)
      secondary to diffuse alveolar-induced acute lung injury. Type I RF occurs with
      ventilation-perfusion mismatch resulting in inadequate oxygenation. Arterial
      oxygen saturation is usually less than 90% despite supplemental fraction of
      inspired oxygen (FIO(2)) greater than 60%. Type I RF may occur as a result of
      injury to the lung parenchyma caused by infection, toxins, pulmonary edema,
      pulmonary hemorrhage, aspiration of gastric contents, and respiratory distress
      syndrome. Whatever the inciting element, the typical pathophysiology of type I RF
      involves damage to the alveolar-capillary membrane causing an inflammatory
      cascade of events. The extent of lung injury determines its severity as well as
      management. Invasive mechanical ventilation support is required in most cases,
      but when the patient is hemodynamically stable and lung injury is mild or
      moderate, noninvasive positive pressure ventilation may provide adequate
      ventilation support. Despite the ventilation type chosen, management requires a
      multidisciplinary team approach and a high level of care.

PMID- 22407369
TI  - Management of a patient with severe sepsis.
AB  - Severe sepsis and septic shock affect more than 700,000 people annually and
      represent approximately $17 billion annually in health care costs. Mortality in
      patients with 3 or more failed organs is up to 70%. Early identification and
      prevention of severe sepsis and septic shock are key factors in impacting
      mortality rates. Health care providers must be knowledgeable in early
      identification and aggressive management. This case presentation outlines the
      components of care identified in the literature in the early and ongoing
      management of patients with severe sepsis and septic shock.

PMID- 22407370
TI  - Penetrating head injury.
AB  - Traumatic brain injury affects more than 1 million civilians annually. Functional
      outcomes in this population are less than favorable. This case report describes a
      patient with a penetrating injury to the head and brain from a gunshot wound
      including the pathophysiology of injury and outlines evidence-based management
      guidelines to provide comprehensive care.

PMID- 22407371
TI  - Stent thrombosis in a clopidogrel nonresponder.
AB  - Stent thrombosis is a known complication of percutaneous coronary intervention
      (PCI) following coronary stent deployment. Dual antiplatelet therapy is standard
      of care following PCI, however, recent studies demonstrate marked variability in
      platelet response to clopidogrel. This case study explores the management of a
      clopidogrel nonresponder who presented with recurrent stent thrombosis despite
      traditional pharmacologic management.

PMID- 22407372
TI  - Pneumonia and encephalopathy in a patient with progressing Parkinson's disease
      and dementia.
AB  - The aging of the US population poses complex management issues for the health
      care provider in the acute and subacute setting. Although management guidelines
      exist to guide the treatment of individual disease processes, addressing goals of
      care in an aging patient with multiple comorbidities requires conversations
      unique to each patient and family. This case study examines the care of a patient
      with Parkinson's disease, dementia, and pneumonia admitted to the intensive care
      unit for altered mental status and metabolic encephalopathy. The pathophysiology
      and management of Parkinson's disease, dementia, community-acquired pneumonia,
      and dysphagia will be reviewed.

PMID- 22407373
TI  - Acute pulmonary embolism.
AB  - Venous thromboembolism is the third leading cause of cardiovascular death in the
      United States and is the second leading cause of death among hospitalized cancer
      patients. Continued controversy exists regarding the role of thrombolytic therapy
      among patients with acute pulmonary embolism. Limited research exists on
      thrombolytic therapy in this setting, most of which has focused on symptoms,
      including right ventricular function, hemodynamic status, and
      electrocardiographic changes. However, these studies have excluded patients with
      a known malignancy. Presented is an interesting case of a patient, in remission
      from breast cancer, who presented to the emergency department with symptomatic
      pulmonary emboli. The presentation, medical management, and consequences of the
      treatment have been discussed. Also, a brief review of the literature is
      presented regarding the treatment of acute pulmonary embolism.

PMID- 22407374
TI  - Acute chest syndrome of sickle cell disease.
AB  - As patients with sickle cell anemia (SCA) are living longer, health care
      practitioners increasingly manage the chronic effects of the disease. Although
      significant strides in management of children with SCA over the past decade
      resulted in decreased mortality, less research exists to guide the care of the
      adult with complications from the disease. This case study reviews the care of a
      young woman with SCA admitted to the hospital for vaso-occlusive crisis with
      subsequent acute chest syndrome and acute respiratory distress syndrome. The
      pathophysiology and management of SCA, vaso-occlusive crisis, and pulmonary and
      neurologic complications of the disease are discussed.

PMID- 22407375
TI  - Esophageal rupture: Boerhaave syndrome.
AB  - Boerhaave syndrome is a rarely occurring condition with a high mortality rate if
      not diagnosed in a timely manner. Patients with this condition complain primarily
      of chest pain, and practitioners should consider esophageal rupture as a
      differential diagnosis during the initial diagnostic evaluation. Most treatment
      modalities have been derived from case studies, as there are no published reports
      on randomized controlled trials specifically dedicated to the treatment of
      Boerhaave syndrome. This case presentation includes the pathophysiology of
      esophageal rupture and the management pathways that have been shown to be
      successful based on current literature.

PMID- 22407376
TI  - Tube to freedom: use of a venting jejunostomy in a patient with chronic
      intestinal pseudo-obstruction.

PMID- 22407377
TI  - Equivalent outcomes after anatomical and non-anatomical resection of small
      hepatocellular carcinoma in patients with preserved liver function.
AB  - BACKGROUND: Although anatomical resection (AR) is considered better than non
      anatomical resection (NAR) for the treatment for hepatocellular carcinoma (HCC),
      there is only limited evidence in support of this argument. AIM: The aim of this
      study was to investigate whether AR is superior to NAR regarding postoperative
      outcomes in patients with small solitary HCC and preserved liver function.
      METHODS: The study subjects were 92 curatively-resected patients with adequate
      liver function reserve (indocyanine green retention rate at 15 min <15%,
      prothrombin time >70%, serum albumin >3.5 g/dl) and macroscopically small (<=3.0
      cm) solitary HCC without macroscopic vascular invasion; 30 patients underwent AR
      and 62 patients NAR. Postoperative short-term outcomes including mortality and
      morbidity and long-term outcomes were compared in the two groups. RESULTS: There
      was no significant difference in clinicopathological background in the two
      groups. Although resected liver volume was significantly larger in the AR group
      than the NAR group (p < 0.0001), no significant differences were detected in the
      incidence of mortality or morbidity. For long-term outcomes, there were no
      significant differences between the two groups in disease-free survival or
      overall survival. Multivariate analysis showed that the extent of surgical
      procedure was not a significant prognostic factor for disease-free or overall
      survival. CONCLUSIONS: AR of a solitary small HCC did not carry postoperative
      outcome advantages compared with NAR in patients with preserved liver function.
      We recommend NAR for hepatic resection of small solitary HCC in patients with
      preserved liver function.

PMID- 22407378
TI  - Dopamine, the kidney, and hypertension.
AB  - There is increasing evidence that the intrarenal dopaminergic system plays an
      important role in the regulation of blood pressure, and defects in dopamine
      signaling appear to be involved in the development of hypertension. Recent
      experimental models have definitively demonstrated that abnormalities in
      intrarenal dopamine production or receptor signaling can predispose to salt
      sensitive hypertension and a dysregulated renin-angiotensin system. In addition,
      studies in both experimental animal models and in humans with salt-sensitive
      hypertension implicate abnormalities in dopamine receptor regulation due to
      receptor desensitization resulting from increased G-protein receptor kinase 4
      (GRK4) activity. Functional polymorphisms that predispose to increased basal GRK4
      activity both decrease dopamine receptor activity and increase angiotensin II
      type 1 (AT1) receptor activity and are associated with essential hypertension in
      a number of different human cohorts.

PMID- 22407379
TI  - Effects of morning compared with evening bright light administration to
      ameliorate short-photoperiod induced depression- and anxiety-like behaviors in a
      diurnal rodent model.
AB  - The lack of appropriate animal models for affective disorders is a major factor
      hindering better understanding of the underlying pathologies and the development
      of more efficacious treatments. Because circadian rhythms play an important role
      in affective disorders, we recently suggested that diurnal rodents can be
      advantageous as model animals. We found that in diurnal rodents, short
      photoperiod induces depression- and anxiety-like behaviors, with similarities to
      human seasonal affective disorder. In a pilot study we also found that these
      behaviors are ameliorated by morning bright light administration. In the present
      study we further evaluated the effects of morning and evening bright light
      administration on short photoperiod-induced depression- and anxiety-like
      behaviors in diurnal fat sand rats. Animals were maintained under short (5L:19D)
      or neutral (12L:12D) photoperiod and treated with morning or evening bright light
      or red dim light as control. Morning bright light ameliorated the behavioral
      deficits in the elevated plus maze and social interaction tests whereas evening
      bright light was effective only in the social interaction test. This is the first
      detailed presentation of the effects of bright light treatment in an animal model
      and a clear demonstration to the advantages of utilizing diurnal rodents to study
      interactions between circadian rhythms and affect.

PMID- 22407381
TI  - Transnasal endoscopy for direct visual control of esophageal stent placement
      without fluoroscopy.
AB  - Placement of self-expanding metal stents (SEMSs) is a well-established treatment
      for esophageal stenosis and postoperative anastomotic leaks. Conventional
      endoscopic procedures for SEMS placement require fluoroscopic guidance, but
      transnasal endoscopy (TNE) with ultraslim endoscopes may allow precise stent
      release under direct visual control without the need for fluoroscopy. This
      prospectively collected data investigated the feasibility and safety of TNE
      guided SEMS placement without fluoroscopy. Between March 2009 and February 2011,
      20 consecutive patients underwent TNE-guided SEMS placement without fluoroscopy.
      The technical success rate was 100 % and no fluoroscopy was required during the
      procedures. Five patients underwent SEMS placement as a bedside procedure in the
      intensive care unit. The mean intervention time was 13.4 minutes (range 6 - 26)
      and there were no early complications. In summary, TNE-guided SEMS placement
      allows precise stent placement without fluoroscopic control and can therefore be
      performed as a simple bedside procedure.

PMID- 22407380
TI  - Different effects of histone deacetylase inhibitors nicotinamide and trichostatin
      A (TSA) in C17.2 neural stem cells.
AB  - Histone deacetylase inhibitors are involved in proliferation, apoptosis, cell
      cycle, mRNA transcription, and protein expression in various cells. However, the
      molecular mechanism underlying such functions is still not fully clear. In this
      study, we used C17.2 neural stem cell (NSC) line as a model to evaluate the
      effects of nicotinamide and trichostatin A (TSA) on cell characteristics. Results
      show that nicotinamide and TSA greatly inhibit cell growth, lead to cell
      morphology changes, and effectively induce cell apoptosis in a dose-dependent
      manner. Western blot analyses confirmed that nicotinamide significantly decreases
      the expression of bcl-2 and p38. Further insight into the molecular mechanisms
      shows the suppression of phosphorylation in eukaryotic initiation factor 4E
      binding protein 1 (4EBP1) by nicotinamide, whereas, an increased expression of
      bcl-2 and p38 and phosphorylation of 4EBP1 by TSA. However, both nicotinamide and
      TSA significantly increase the expression of cytochrome c (cyt c). These results
      strongly suggest that bcl-2, p38, cyt c, and p-4EBP1 could suppress proliferation
      and induce apoptosis of C17.2 NSCs mediated by histone deacetylase inhibitors,
      nicotinamide and TSA, involving different molecular mechanisms.

PMID- 22407382
TI  - Single-step endoscopic ultrasonography-guided drainage of peripancreatic fluid
      collections with a single self-expandable metal stent and standard linear
      echoendoscope.
AB  - Endoscopic ultrasonography (EUS)-guided drainage of peripancreatic fluid
      collections (PFCs) is a well described alternative to surgery or percutaneous
      drainage. However, it is limited by the requirement for a large working channel
      that allows multiple plastic stent placement, which is only commercially
      available on therapeutic linear echoendoscopes. Herein, we describe the drainage
      of PFCs with a single self-expandable metal stent (SEMS) using a single-step
      technique and standard linear echoendoscope. Seven cases were identified during a
      retrospective chart review, and included all patients who had undergone EUS
      guided drainage of PFCs during a 6-month period. The mean age was 46 years (range
      25 - 70 years) and all patients were symptomatic. The mean diameter of PFCs was 8
      cm (range 4.1 - 12.5 cm). Previous percutaneous drainage had failed in three
      patients. A total of 10 PFCs were drained. Three patients had two cysts drained
      by the same stent and one patient had two separate procedures to drain two
      distinct cysts. The SEMS was in place for a mean of 13 weeks (range 4 - 34
      weeks). Successful placement of SEMS was achieved in all seven cases. Patients
      were followed for a mean of 18 weeks (range 7 - 35 weeks), and symptom
      improvement was achieved in all cases. Complete resolution of PFC was achieved in
      9 /10 cysts. No complications were encountered. Single-step EUS-guided drainage
      of PFCs using a single 10-mm SEMS and a standard linear echoendoscope appears to
      be a feasible endoscopic technique with excellent technical and clinical success
      rates.

PMID- 22407383
TI  - A pilot study to assess mediastinal emphysema after esophageal endoscopic
      submucosal dissection with carbon dioxide insufflation.
AB  - BACKGROUND AND AIMS: Mediastinal emphysema sometimes develops following
      esophageal endoscopic submucosal dissection (ESD) without perforation because the
      esophagus has no serosa. Carbon dioxide (CO2) insufflation during esophageal ESD
      may reduce the incidence of mediastinal emphysema. The aim of the present study
      was to compare the incidence and severity of post-ESD mediastinal emphysema in
      patients receiving CO2 insufflation vs. standard air insufflation during
      esophageal ESD. PATIENTS AND METHODS: A total of 27 patients who had undergone
      esophageal ESD with insufflation of CO2 between July 2009 and March 2010 were
      enrolled in this study (CO2 group). Another 105 patients who had undergone
      esophageal ESD with air insufflation between March 2004 and May 2009 were
      included as historical controls (air group). Multi-detector row computed
      tomography (MDCT) was carried out immediately after ESD. A conventional chest
      radiograph was taken the next day. Mediastinal emphysema findings on MDCT and
      radiography were compared between the groups. RESULTS: Mediastinal emphysema
      detected by chest radiography was 0 % in the CO2 group vs. 6.6 % in the air group
      (n.s.). Mediastinal emphysema on MDCT was significantly less frequent in the CO2
      group compared with the air group (30 % vs. 63 %; P = 0.002). The severity of
      mediastinal emphysema also tended to be lower in the CO2 group. CONCLUSIONS:
      Whereas mediastinal emphysema detected by radiography is not so common, MDCT
      immediately after ESD revealed a certain prevalence of post-ESD mediastinal
      emphysema. Insufflation of CO2 rather than air during esophageal ESD
      significantly reduced postprocedural mediastinal emphysema. CO2 can be considered
      as insufflating gas for esophageal ESD.

PMID- 22407384
TI  - Health Utilities Index Mark 3 (HUI3) demonstrated construct validity in a
      Nigerian population with hypertension.
AB  - PURPOSE: This study seeks to establish the construct validity of Health Utilities
      Index Mark 3 (HUI3)--a health state utility measure--in a Nigerian population of
      hypertensive patients. METHODS: A descriptive cross-sectional study was conducted
      in a population of hypertensive patients in two tertiary hospitals located in
      South-Eastern Nigeria. A priori hypotheses were tested to establish construct
      validity. RESULTS: A total of 384 participants were interviewed. Hypertensive
      patients with stroke or coronary heart disease (CHD) had a lower overall utility
      value compared to those with hypertension alone. There was a significant
      difference in group means of 0.53 (95 % confidence interval of 0.44-0.62); t =
      11.8, p < 0.01, between participants that had hypertension alone and participants
      with hypertension and stroke. Also, there was a significant difference in group
      means of 0.44 (95 % confidence interval of 0.34-0.56); t = 8.2, p < 0.01, between
      participants that had hypertension alone and participants with hypertension and
      CHD. Generally, there was a significant health-related quality of life deficit
      among patients with severe clinical variables compared to those with milder
      clinical variables. CONCLUSION: HUI3 demonstrated constructed validity among a
      population of Nigerian patients with high blood pressure.

PMID- 22407385
TI  - Interdisciplinary endoscopic assisted surgery of a patient with a complete
      transorbital intracranial impalement through the dominant hemisphere.

PMID- 22407386
TI  - Osteogenic response of mesenchymal stem cells to continuous mechanical strain is
      dependent on ERK1/2-Runx2 signaling.
AB  - Mechanical stimuli are responsible for bone remodeling during orthodontic tooth
      movement. The role of mechanical stimulation in the regulation of the fate of
      bone mesenchymal stem cells (BMSCs) is of interest in bone regeneration and
      tissue engineering applications. However, the signaling pathway involved in
      strain-induced biochemical events in BMSCs is not well established and can be
      controversial. This study investigated strain-induced proliferation and
      differentiation of BMSCs, as well as the mechanism of mechanotransduction. BMSCs
      were exposed to continuous mechanical strain (CMS) of 10% at 1 Hz. The results
      showed that CMS reduced the proliferation of BMSCs and stimulated osteogenic
      differentiation by activating Runx2, followed by increased alkaline phosphatase
      (ALP) activity and mRNA expression of osteogenesis-related genes (ALP, collagen
      type I and osteocalcin). Furthermore, the phosphorylation level of extracellular
      regulated protein kinase (ERK)1/2 increased significantly at the onset of strain.
      However, the presence of U0126, a selective inhibitor of ERK1/2, blocked the
      induction of Runx2 and subsequent osteogenic events. These findings demonstrate
      that CMS regulated Runx2 activation and favored osteoblast differentiation
      through activation of the ERK1/2 signaling pathway. These results will contribute
      to a better understanding of strain-induced bone remodeling and will form the
      basis for the correct choice of applied force in orthodontic treatment.

PMID- 22407388
TI  - Factors influencing intermethod agreement between goldmann applanation, pascal
      dynamic contour, and ocular response analyzer tonometry.
AB  - PURPOSE: To examine factors that influence intraocular pressure (IOP) measurement
      agreement between Goldmann applanation (GAT), Ocular Response Analyzer (ORA), and
      Pascal Dynamic Contour tonometers (DCT). PATIENTS AND METHODS: In subjects who
      were diagnosed with primary open-angle glaucoma, ocular hypertension, glaucoma
      suspect, and normal, we used ORA, DCT, and GAT to obtain corneal hysteresis (CH),
      corneal resistance factor (CRF), ocular pulse amplitude, and 4 IOP values (ORA
      IOPcc; ORA-IOPg; DCT-IOP; and GAT-IOP.) We also obtained corneal curvature,
      corneal thickness, axial length, retinal nerve fiber layer thickness, visual
      field parameters, diabetes diagnostic status, and topical IOP-lowering treatment
      data. Analysis of variance, Bland-Altman, and regression analyses were used to
      examine IOP agreement and associated factors. RESULTS: In 243 eyes of the 243
      subjects, mean DCT-IOP (18.73+/-4.92) was not different from mean ORA-IOPcc
      (18.96+/-5.41) but both were significantly higher than ORA-IOPg (16.97+/-5.49)
      and GAT-IOP (16.37+/-4.97). In multivariate regression models, intermethod
      differences between IOPg, IOPcc, and DCT-IOP were explained almost completely by
      variations in CH, CRF, and level of IOP (r(2)=0.98 to 0.99); conversely,
      intermethod variability between GAT-IOP and the other 3 IOP metrics was only
      partially explained by the factors evaluated in this study (r(2)=0.31 to 0.65).
      CONCLUSIONS: Consistent with other studies, we found that the 4 IOP variables
      examined in this study are not interchangeable. The most consistent confounders
      of IOP measurement agreement were the ORA-measured corneal parameters, CH and
      CRF. Thus, accounting for these factors may be important in efforts to obtain
      accurate transcorneal estimates of IOP.

PMID- 22407387
TI  - Genome-wide analysis of microRNAs in rubber tree (Hevea brasiliensis L.) using
      high-throughput sequencing.
AB  - MicroRNAs (miRNAs) are short RNAs with essential roles in gene regulation in
      various organisms including higher plants. In contrast to the vast information on
      miRNAs from many economically important plants, almost nothing has been reported
      on the identification or analysis of miRNAs from rubber tree (Hevea brasiliensis
      L.), the most important natural rubber-producing crop. To identify miRNAs and
      their target genes in rubber tree, high-throughput sequencing combined with a
      computational approach was performed. Four small RNA libraries were constructed
      for deep sequencing from mature and young leaves of two rubber tree clones, PB
      260 and PB 217, which provide high and low latex yield, respectively. 115 miRNAs
      belonging to 56 known miRNA families were identified, and northern hybridization
      validated miRNA expression and revealed developmental stage-dependent and clone
      specific expression for some miRNAs. We took advantage of the newly released
      rubber tree genome assembly and predicted 20 novel miRNAs. Further, computational
      analysis uncovered potential targets of the known and novel miRNAs. Predicted
      target genes included not only transcription factors but also genes involved in
      various biological processes including stress responses, primary and secondary
      metabolism, and signal transduction. In particular, genes with roles in rubber
      biosynthesis are predicted targets of miRNAs. This study provides a basic catalog
      of miRNAs and their targets in rubber tree to facilitate future improvement and
      exploitation of rubber tree.

PMID- 22407389
TI  - Fixation of external drainage device with injectable shape-memory alloy clips.
AB  - PURPOSE: To describe a novel surgical technique and novel surgical
      instrumentation for fixating an extraocular drainage device used for glaucoma
      filtering surgery. MATERIALS AND METHODS: The technique was performed in a
      laboratory setting using ex-vivo porcine eyes. We describe the surgical technique
      of using injectable, 25-gauge shape-memory clip system to fixate an Ahmed
      drainage device. RESULTS: The use of an injectable, shape-memory alloy clip
      provides the advantages of rapid, easy deployment and decreased risk of late
      suture failure. Importantly, the injectable, shape-memory clips can be used in
      surgical situations where suturing is difficult and time intensive, such as those
      encountered during glaucoma drainage device placement. CONCLUSIONS: The use of an
      injectable, shape-memory alloy clip is a promising new surgical tool and
      technique for fixating an extraocular drainage device used for glaucoma surgery.

PMID- 22407390
TI  - Quality of life of medically versus surgically treated glaucoma patients.
AB  - PURPOSE: To assess and compare the impact of medical and surgical glaucoma
      treatments on patients' health-related Quality of Life (QoL). MATERIALS AND
      METHODS: We used the 25-question version of the National Eye Institute Visual
      Functioning Questionnaire (NEI VFQ-25) for this cross-sectional study. Patients
      were divided into 3 groups: 1 (medical treatment); 2 (surgical treatment), and 3
      (medical and surgical treatment). Comparisons among groups were carried out for
      demographic and clinical characteristics and for the NEI VFQ-25 scores. RESULTS:
      Of the 240 invited patients, 225 were enrolled for this study. Groups were
      homogenous for age, sex, race, type of glaucoma, and level of education. The mean
      overall score was 78.46, 65.85, and 60.51 for groups 1, 2, and 3, respectively
      (P<0.001). Type of therapy, visual acuity, and comorbidity were associated with
      QoL scores. When controlled by glaucoma stages, surgery had a negative impact on
      the QoL only in early glaucoma. CONCLUSIONS: Glaucoma surgery is associated with
      a lower QoL in patients with early glaucoma due mainly to the psychological
      burden. In moderate and advanced glaucomas, the QoL scores did not differ between
      the surgical and the medical therapy groups.

PMID- 22407392
TI  - Frequency and risk factors for neovascular glaucoma after vitrectomy in eyes with
      proliferative diabetic retinopathy.
AB  - PURPOSE: To investigate the rate and risk factors for neovascular glaucoma (NVG)
      after vitrectomy in proliferative diabetic retinopathy (PDR). METHODS: Five
      hundred and twelve patients (512 eyes) with PDR who underwent vitrectomy between
      January 1, 2003 and June 30, 2009 at Kumamoto University Hospital, Japan, were
      retrospectively evaluated. Postoperative NVG was defined as neovascularization in
      the anterior segment and intraocular pressure (IOP) >= 22 mm Hg after vitrectomy.
      Kaplan-Meier survival analysis was applied to calculate the rate of NVG after
      vitrectomy. Risk factors for NVG after vitrectomy were identified by
      multivariable analysis using the Cox proportional hazards model. RESULTS: The
      mean follow-up period was 422 days. Twenty-seven of 512 patients (5.3%) developed
      postoperative NVG after vitrectomy. The probability of NVG occurrence at 6 and 12
      months after vitrectomy was 6.0% and 7.1%, respectively. Male sex [relative risk
      (RR)=4.247; P=0.0032), younger age (RR=0.956/y; P=0.0237), higher baseline IOP
      (RR=1.203/mm Hg; P=0.0335), preoperative neovascularization in the anterior
      chamber angle (RR=8.899; P<0.0001), and presence of NVG in the fellow eye
      (RR=5.355; P=0.0013) were significant risk factors for postoperative NVG.
      CONCLUSIONS: The frequency of NVG in PDR eyes within 1 year after vitrectomy was
      estimated as 7.1%. The risk is independently associated with male sex, younger
      age, higher baseline IOP, preoperative neovascularization in the angle, and NVG
      in the fellow eye.

PMID- 22407393
TI  - Comparison of the utility of Pascal dynamic contour tonometry with Goldmann
      applanation tonometry in routine clinical practice.
AB  - PURPOSE: To compare the utility of Pascal dynamic contour tonometry with Goldmann
      applanation tonometry in routine practice METHODS: In a prospective study, 10
      clinicians recruited 97 patients attending outpatient ophthalmology appointments.
      Intraocular pressure was measured with both Pascal and Goldmann tonometry in a
      randomized order. The time taken with each instrument, the number of measurements
      required to obtain a satisfactory Pascal reading (Q1 to Q3) and the quality value
      of this reading were recorded. Both the difficulty experienced by the clinician
      and patient experience for each instrument were assessed. RESULTS: Satisfactory
      Pascal measurements were obtained for 181 of 194 eyes (93%). For these eyes there
      was no significant difference in mean measured intraocular pressure between
      Pascal (15.95+/-3.20) and Goldmann (16.37+/-3.51) (mean difference 0.43 mm Hg,
      P=0.26) tonometry. The median number of attempts required to obtain a
      satisfactory Pascal measurement was 2 (range, 1 to 10). The time taken to obtain
      bilateral satisfactory Pascal readings was 2.76+/-1.53 minutes (range, 0.5 to 7
      min), compared with 0.82+/-0.43 minutes (range, 0.5 to 3 min) for Goldmann
      tonometry (P<0.001). For these patients, clinicians scored the difficulty of
      tonometry as 3.24+/-1.97 for Pascal (1=very easy, 10=very difficult) and 1.28+/
      0.85 for Goldmann (P<0.0001). The mean score (1=no discomfort, 10=extremely
      unpleasant) given by patients was 1.31+/-0.64 for Goldmann and 2.11+/-1.83 for
      Pascal tonometry (P<0.0001). CONCLUSIONS: Clinicians found Pascal tonometry
      significantly more time consuming and difficult than Goldmann tonometry in
      routine practice. Most eyes required repeated Pascal measurements, and for some
      an acceptable result was not obtained. Both types of tonometry were well
      tolerated by patients.

PMID- 22407394
TI  - Changes in anterior segment parameters after insertion of Ex-PRESS miniature
      glaucoma implant.
AB  - PURPOSE: The aim of this study was to evaluate the effect of Ex-PRESS Miniature
      Glaucoma Implant surgery on corneal curvature and anterior segment parameters
      obtained with the Pentacam rotating Scheimpflug camera (Oculus Inc.).
      PATIENTS/METHODS: In this prospective study, a total of 19 eyes of 19 consecutive
      patients (11 men, 8 women) were evaluated preoperatively, on the first
      postoperative day, and at 1 week, 1 month, and 3 months postoperatively with the
      Pentacam. We compared measurements of anterior and posterior corneal curvature,
      anterior and posterior corneal astigmatism, anterior chamber depth (ACD),
      anterior chamber volume (ACV), and anterior chamber angle before and after
      surgery. All study eyes were pseudophakic. RESULTS: Intraocular pressure
      decreased significantly from 31.9+/-10.1 mmHg preoperatively to 6.1+/-5.7 mmHg on
      the first postoperative day (P<0.0001) and 15.7+/-3.6 mmHg at 3 months after
      surgery (P=0.0011). On the first postoperative day, the anterior corneal
      astigmatism increased from 2.6+/-3.3 to 4.7+/-3.1 D (P=0.19), the posterior
      corneal astigmatism increased from 0.4+/-0.2 to 0.9+/-0.5 D (P=0.008), the ACD
      decreased from 4.3+/-0.7 to 3.5+/-1 mm (P=0.015), and the ACV decreased from
      193+/-35 to 160+/-49 mm (P=0.006). All of these changes in anterior segment
      parameters were not statistically significant at 3 months after surgery.
      CONCLUSIONS: Ex-PRESS Miniature Glaucoma Implant surgery significantly decreased
      intraocular pressure and had a transient effect on anterior segment parameters.
      Corneal curvatures, ACD, ACV, and anterior chamber angle were not affected at 3
      months of follow-up.

PMID- 22407395
TI  - Ability of fourier-domain optical coherence tomography to detect retinal ganglion
      cell complex atrophy in glaucoma patients.
AB  - PURPOSE: To evaluate the diagnostic ability of Fourier-domain optical coherence
      tomography (FD-OCT) measurements in both normal individuals and patients with
      different stages of glaucoma. PATIENTS AND METHODS: A total of 113 patients
      diagnosed with glaucoma and classified into different stages of glaucoma
      according to Glaucoma Staging System 2 and 30 healthy individuals were included
      in this study. In all patients, parameters of both the retinal ganglion cell
      complex (GCC) and the peripapillary retinal nerve fiber layer were measured by FD
      OCT (RTVue-100). Comparisons were made from measurements in patients with
      different stages of glaucoma. RESULTS: Both GCC and retinal nerve fiber layer
      thickness values of patients with glaucoma were statistically significantly lower
      compared with those of healthy individuals. As the stage of glaucoma progressed,
      the mean GCC and retinal nerve fiber layer thickness values decreased.
      CONCLUSIONS: GCC and retinal nerve fiber layer thickness measurements performed
      by FD-OCT showed high diagnostic ability in detecting glaucoma. Mean thickness
      values can be determined for each glaucoma stage.

PMID- 22407396
TI  - Expression of ALDH1 in axillary lymph node metastases is a prognostic factor of
      poor clinical outcome in breast cancer patients with 1-3 lymph node metastases.
AB  - BACKGROUND: Recently, evidence in support of the cancer stem cell (CSC)
      hypothesis has been accumulating. On the other hand, it has been reported that
      the expression of aldehyde dehydrogenase 1 (ALDH1) in primary breast cancer is a
      powerful predictor of a poor clinical outcome, and that breast cancer stem cells
      express ALDH1. According to the CSC hypothesis, development of metastases
      requires the dissemination of CSC that may remain dormant and be reactivated to
      cause tumor recurrence. In this study, we investigated whether the detection of
      CSC in axillary lymph node metastases (ALNM) might be a significant prognostic
      factor in patients with breast cancer. METHODS: From 1998 to 2006, 40 primary
      breast cancer patients with ALNM, the number of metastatic nodes varying in
      number from 1 to 3, underwent surgery at Okayama University; of these, 15
      patients developed tumor recurrence. We retrospectively evaluated the common
      clinicopathological features and the expression of ER, HER2, ALDH1, and Ki67 in
      both the primary lesions and the ALNM, and analyzed the correlations between the
      expression of these biological markers and the disease-free survival (DFS).
      RESULTS: Expression of ALDH1 in the ALNM was significantly associated with the
      DFS (P = 0.037). CONCLUSION: Evaluation of biomarker expression in ALNM could be
      useful for prognosis in breast cancer patients with 1-3 metastatic lymph nodes.

PMID- 22407397
TI  - FTY720 mediates activation suppression and G(0)/G (1) cell cycle arrest in a
      concanavalin A-induced mouse lymphocyte pan-activation model.
AB  - OBJECTIVE: FTY720 is a potent drug for multiple sclerosis treatment. To
      biologically address its possible applications to more generalized diseases with
      aberrant inflammation, we are testing whether FTY720 can function as a lymphocyte
      cell cycle blocker and activation suppressor via a concanavalin A (ConA)-mediated
      mouse lymphocyte pan-activation model. METHODS: Mouse lymphocytes were obtained
      from lymph nodes and subjected to ConA and/or FTY720 treatment. Cell viability
      was assayed by MTT and mitochondrial assays. Early and late activation, cell
      cycle, proliferation and intracellular Ca(2+) concentration ([Ca(2+)](i)) were
      analyzed by flow cytometry. RESULTS: At concentrations of less than 500 nM,
      FTY720 significantly down-regulated both CD69 and CD25 expressions of T cells, as
      well as inhibiting proliferation of activated lymphocytes. In addition, FTY720
      blocked the ConA-induced mitogenesis, exhibiting lymphocyte G(0)/G(1) phase cell
      cycle arrest with significant reduction of cells in S and G(2)/M phases.
      Meanwhile, a significant decline in [Ca(2+)](i) was observed. The correlation of
      [Ca(2+)](i) and cell cycle arrest were validated by employing a [Ca(2+)](i)
      inhibitor SK&F 96365 and testing with and without FTY720 treatment. CONCLUSION:
      We demonstrated that FTY720 induces G(0)/G(1) phase cell cycle arrest, resulting
      in proliferation inhibition upon lymphocyte pan-activation, which may be related
      to reduction of overall intracellular Ca(2+) load.

PMID- 22407398
TI  - Evaluation of the anti-oxidant properties of a SOD-mimic Mn-complex in activated
      macrophages.
AB  - SOD-mimics are small complexes that reproduce the activity of superoxide
      dismutases, natural proteins that catalytically dismutate the superoxide anion.
      Activated macrophages, which produce ROS and RNS fluxes, constitute a relevant
      model to challenge antioxidant activity in a cellular context and were used to
      test a Mn-complex which was shown to efficiently alter the flow of O(2)(-), ONOO(
      ) and H(2)O(2).

PMID- 22407399
TI  - A security and privacy preserving e-prescription system based on smart cards.
AB  - In 2002, Ateniese and Medeiros proposed an e-prescription system, in which the
      patient can store e-prescription and related information using smart card.
      Latter, Yang et al. proposed a novel smart-card based e-prescription system based
      on Ateniese and Medeiros's system in 2004. Yang et al. considered the privacy
      issues of prescription data and adopted the concept of a group signature to
      provide patient's privacy protection. To make the e-prescription system more
      realistic, they further applied a proxy signature to allow a patient to delegate
      his signing capability to other people. This paper proposed a novel security and
      privacy preserving e-prescription system model based on smart cards. A new role,
      chemist, is included in the system model for settling the medicine dispute. We
      further presented a concrete identity-based (ID-based) group signature scheme and
      an ID-based proxy signature scheme to realize the proposed model. Main property
      of an ID-based system is that public key is simple user's identity and can be
      verified without extra public key certificates. Our ID-based group signature
      scheme can allow doctors to sign e-prescription anonymously. In a case of a
      medical dispute, identities of the doctors can be identified. The proposed ID
      based proxy signature scheme can improve signing delegation and allows a
      delegation chain. The proposed e-prescription system based on our proposed two
      cryptographic schemes is more practical and efficient than Yang et al.'s system
      in terms of security, communication overheads, computational costs, practical
      considerations.

PMID- 22407400
TI  - Identification of patients likely to benefit from metastasectomy in stage IV
      colorectal cancer.
AB  - PURPOSE: The aim of the present study was to determine selection criteria for
      patients with stage IV colorectal cancer (CRC) who were likely to show survival
      benefits of metastasectomy. METHODS: Clinicopathological data of 119 patients
      with stage IV CRC who underwent primary CRC resection were retrospectively
      reviewed. The prognostic factors were analyzed according to the disease
      resectability status, and patients likely to show survival benefits of
      metastasectomy were identified. RESULTS: Metastasectomy was performed in 63
      patients. Among these patients, R0 resection was reported in 55 patients, who
      comprised the curable group. The other 64 patients comprised the noncurable
      group. For the noncurable group, postoperative chemotherapy was identified as the
      only significant prognostic factor. In the curable group, T stage, histological
      type, elevated serum carcinoembryonic antigen (CEA) level and the presence of
      extra hepatic disease were identified as independent prognostic factors. Patients
      within the curable group were further classified into a low-risk group (zero to
      two prognostic factors) and a high-risk group (three or more prognostic factors).
      The overall survival (OS) of the high risk patients in the curable group was as
      poor as that of the patients in the noncurable group. CONCLUSIONS: Stage IV CRC
      patients consisted of heterogeneous populations who had different prognostic
      factors, stratified by the disease resectability status. No prognostic benefit of
      metastasectomy was observed in high-risk patients undergoing curative
      metastasectomy. These results suggested that patients showing survival benefits
      of metastasectomy can be identified by considering the prognostic factors in
      patients undergoing curative metastasectomy.

PMID- 22407401
TI  - The aza-Morita-Baylis-Hillman reaction of electronically and sterically
      deactivated substrates.
AB  - The aza-Morita-Baylis-Hillman (azaMBH) reaction has been studied for
      electronically and sterically deactivated Michael acceptors. It is found that
      electronically deactivated systems can be converted with electron-rich phosphanes
      and pyridines as catalysts equally well. For sterically deactivated systems
      clearly better catalytic turnover can be achieved with pyridine catalysts. This
      is in accordance with the calculated affinities of the catalysts towards
      different Michael-acceptors.

PMID- 22407402
TI  - Light history modulates antioxidant and photosynthetic responses of biofilms to
      both natural (light) and chemical (herbicides) stressors.
AB  - In multiple stress situations, the co-occurrence of environmental and chemical
      factors can influence organisms' ability to cope with toxicity. In this context,
      the influence of light adaptation on the response of freshwater biofilms to
      sudden light changes or to herbicides exposure was investigated by determining
      various parameters: diatom community composition, photosynthetic parameters,
      chlorophyll a content, antioxidant enzyme activities. Biofilms were grown in
      microcosms under sub-optimal, saturating, and high light intensities and showed
      already described characteristics of shade/light adaptation (community structure,
      photosynthetic adaptation, etc.). Light history modulated antioxidant and
      photosynthetic responses of biofilms to the stress caused by short-term exposure
      to sudden light changes or to herbicides. First biofilms adapted to sub-optimal
      light intensity (shade-adapted) were found to be more sensitive to an increase in
      light intensity than high-light adapted ones to a reduction in light intensity.
      Second, while light history influenced biofilms' response to glyphosate, it had
      little influence on biofilms' response to copper and none on its response to
      oxyfluorfen. Indeed glyphosate exposure led to a stronger decrease in
      photosynthetic efficiency of shade-adapted biofilms (EC(50) = 11.7 mg L(-1)) than
      of high-light adapted communities (EC(50) = 35.6 mg L(-1)). Copper exposure led
      to an activation of ascorbate peroxidase (APX) in biofilms adapted to sub-optimal
      and saturating light intensity while the protein content decreased in all
      biofilms exposed to copper. Oxyfluorfen toxicity was independent of light history
      provoking an increase in APX activity. In conclusion this study showed that both
      previous exposure to contaminants and physical habitat characteristics might
      influence community tolerance to disturbances strongly.

PMID- 22407403
TI  - Differences in organochlorine accumulation accompanying life history in the
      catadromous eel Anguilla japonica and the marine eel Conger myriaster.
AB  - In order to examine the ecological risk for organic pollutants in diadromous fish
      migrating between sea and freshwater, organochlorine compounds (OCs) were
      determined in the catadromous eel Anguilla japonica having marine, estuarine and
      freshwater residence life histories. The eels were collected in Japanese coastal
      areas. We also compared the OCs accumulation with the marine eel Conger
      myriaster, which has a similar life history as A. japonica in the marine
      environment. The ontogenic changes in the otolith strontium (Sr) and calcium (Ca)
      concentrations were examined along the life history transect to discriminate the
      migration type. There were generally three different patterns, which were
      categorized as 'marine residence' (spent most of their life in the sea and did
      not enter freshwater), 'estuarine residence' (inhabited estuaries or switched
      between different habitats), and 'freshwater residence' (entered and remained in
      freshwater river habitats after arrival in the estuary) according to the otolith
      Sr:Ca ratio. There were generally no correlations between OCs such as
      Dichlorodiphenyltrichloroethanes (DDTs), Hexachlorobenzene (HCB),
      Hexachlorocyclohexanes (HCHs) and Chlordanes (CHLs) accumulation and each
      biological characteristic such as TL, BW and age in A. japonica. A positive
      correlation between the lipid content and concentrations of OCs were found.
      Additionally, the concentrations of HCB, ?HCHs, ?CHLs and ?DDTs in A. japonica
      were significantly higher than those of C. myriaster, associating with the higher
      lipid contents (14% on average) in the former than the latter eels (9% on
      average). A negative linear relationship was found between the otolith Sr:Ca
      ratios and concentration of each OCs in A. japonica. The ecological risk of OCs
      increase as the freshwater residence period in the eel becomes longer. It is
      clear that migratory histories and lipid contents directly affected OCs
      accumulation in the anguillid eels.

PMID- 22407404
TI  - Epidemiological survey and genetic evolution of H9 subtype influenza viruses in
      Shanghai, China, from 2006 to 2010.
AB  - The H9N2 influenza virus is endemic in poultry. We report its occurrence in live
      poultry markets, fair-trade markets and poultry farms in the Shanghai region
      between September 2006 and December 2010. An analysis of partial sequences of the
      HA, NA, PB1, PB2 and NP genes of eleven distinct H9N2 isolates revealed that all
      carried an RSSR motif at the cleavage site of HA, diagnostic of low pathogenicity
      in chickens. A phylogenetic analysis indicated that these isolates are derived
      from the lineage represented by Duck/HK/Y280/97, but they have evolved a range of
      reassortments. Their PB1 and NP sequences resembled those of H5N1 strains,
      indicating a hybrid origin involving both H9 and H5 strains. The HA and NA
      sequences present in all eleven isolates resembled those of the Duck/HK/Y280/97
      like lineage. Infection by H9N2 is commonplace in Shanghai live-poultry markets,
      allowing the viruses to have evolved rapidly.

PMID- 22407405
TI  - Sequence and phylogenetic data indicate that an orthobunyavirus recently detected
      in the Yucatan Peninsula of Mexico is a novel reassortant of Potosi and Cache
      Valley viruses.
AB  - We determined the complete nucleotide sequences of the small (S) and medium (M)
      RNA segments of an orthobunyavirus isolated from mosquitoes in the Yucatan
      Peninsula of Mexico. A 528-nt region of the large (L) RNA segment was also
      sequenced. The S RNA segment has greatest nucleotide identity to the homologous
      region of Cache Valley virus (CVV; 98%) followed by Potosi virus (POTV; 89%) and
      Northway virus (86%). The M RNA segment has 96% nucleotide identity to the
      homologous region of POTV, and less than 74% nucleotide identity to the
      homologous regions of all other orthobunyaviruses for which M segment sequence
      data are available. The L RNA segment has greatest nucleotide identity to the
      homologous region of POTV (98%) followed by CVV (82%) and Tensaw virus (77%).
      These data indicate that the virus, tentatively named Cholul virus (CHLV), is a
      novel reassortant that acquired its S RNA segment from CVV and its M and L RNA
      segments from POTV. Phylogenetic data support this conclusion.

PMID- 22407407
TI  - The significance of the alkene size and the nature of the metal ion in metal
      alkene complexes: a theoretical study.
AB  - Cation interactions with pi-systems are a problem of outstanding contemporary
      interest and the nature of these interactions seems to be quite different for
      transition and main group metal ions. In this paper, we have systematically
      analyzed the contrast in the bonding of Cu(+) and main group metal ions. The
      molecular structures and energetics of the complexes formed by various alkenes (A
      = C(n)H(2n), n = 2-6; C(n)H(2n- 2), n = 3-8 and C(n)H(2n + 2), n = 5-10) and
      metal ions (M = Li(+), Na(+), K(+), Ca(2+), Mg(2+), Cu(+) and Zn(2+)) are
      investigated by employing ab initio post Hartree-Fock (MP2/6-311++G**)
      calculations and are reported in the current study. The study, which also aims to
      evaluate the effect of the size of the alkyl portion attached to the pi-system on
      the complexation energy, indicates a linear relationship between the two. The
      decreasing order of complexation energy with various metal ion-alkene complexes
      follows the order Zn(2+)-A > Mg(2+)-A > Ca(2+)-A > Cu(+)-A > Li(+)-A > Na(+)-A >
      K(+)-A. The increased charge transfer and the electron density at (3,-1)
      intermolecular bond critical point corroborates well with the size of the pi
      system and the complexation energy. The observed deviation from the linear
      dependency of the Cu(+)-A complexes is attributed to the dpi->pi* back bonding
      interaction. An energy decomposition analysis via the reduced variational space
      (RVS) procedure was also carried out to analyze which component among
      polarization, charge transfer, coulomb and exchange repulsion contributes to the
      increase in the complexation energy. The RVS results suggest that the
      polarization component significantly contributes to the increase in the
      complexation energy when the alkene size increases.

PMID- 22407406
TI  - Isolation of yellow catfish beta-actin promoter and generation of transgenic
      yellow catfish expressing enhanced yellow fluorescent protein.
AB  - Yellow catfish (Pelteobagrus fulvidraco Richardson) is one of the most important
      freshwater farmed species in China. However, its small size and slow growth rate
      limit its commercial value. Because genetic engineering has been a powerful tool
      to develop and improve fish traits for aquaculture, we performed transgenic
      research on yellow catfish in order to increase its size and growth rate.
      Performing PCR with degenerate primers, we cloned a genomic fragment comprising
      5'-flanking sequence upstream of the initiation codon of beta-actin gene in
      yellow catfish. The sequence is 1,017 bp long, containing the core sequence of
      proximal promoter including CAAT box, CArG motif and TATA box. Microinjecting the
      transgene construct Tg(beta-actin:eYFP) of the proximal promoter fused to
      enhanced yellow fluorescent protein (eYFP) reporter gene into zebrafish and
      yellow catfish embryos, we found the promoter could drive the reporter to express
      transiently in both embryos at early development. Screening the offspring of five
      transgenic zebrafish founders developed from the embryos microinjected with
      Tg(ycbeta-actin:mCherry) or 19 yellow catfish founders developed from the embryos
      microinjected with Tg(beta-actin:eYFP), we obtained three lines of transgenic
      zebrafish and one transgenic yellow catfish, respectively. Analyzing the
      expression patterns of the reporter genes in transgenic zebrafish (Tg(ycbeta
      actin:mCherry)nju8/+) and transgenic yellow catfish (Tg(beta-actin:eYFP)nju11/+),
      we found the reporters were broadly expressed in both animals. In summary, we
      have established a platform to make transgenic yellow catfish using the proximal
      promoter of its own beta-actin gene. The results will help us to create
      transgenic yellow catfish using "all yellow catfish" transgene constructs.

PMID- 22407408
TI  - Association of multidrug resistance-associated protein 2 single nucleotide
      polymorphism rs12762549 with the basal plasma levels of phase II metabolites of
      isoflavonoids in healthy Japanese individuals.
AB  - OBJECTIVES: Multidrug resistance-associated protein 2 (MRP2; ABCC2) is an ATP
      binding cassette transporter that mediates the efflux of anionic drugs and phase
      II metabolites. Our aim was to elucidate the impact of a single nucleotide
      polymorphism, rs12762549 (G>C), on the in-vivo activity of MRP2. METHODS: Plasma
      specimens collected from 18 healthy volunteers were subjected to an untargeted
      metabolomic analysis using liquid chromatography-mass spectrometry. The role of
      MRP2 in the disposition of substances of interest was then examined in vivo in
      Mrp2-deficient mutant rats (Eisai hyperbilirubinemic rats; EHBRs) and in vitro in
      human MRP2-expressing membrane vesicles. RESULTS: A multivariate analysis model
      using liquid chromatography-mass spectrometry data sets successfully
      differentiated the GG and the CC genotypes of rs12762549. The C allele is
      associated with the basal plasma levels of the five phase II metabolites of
      genistein and dihydrogenistein. Such phase II metabolites were also accumulated
      in EHBR, compared with normal rats, partly because of the reduced biliary
      excretion. Following oral administration of genistein and daidzein, the plasma
      concentrations of total genistein and total daidzein, which were mainly accounted
      for by sulfoglucuronide conjugates, were markedly higher in EHBR than in normal
      rats. ATP-dependent uptake of sulfoglucuronides and glucuronides of the
      isoflavonoids was observed only in MRP2-expressing membrane vesicles. CONCLUSION:
      MRP2 plays a significant role in preventing the accumulation of phase II
      metabolites of isoflavonoids. The rs12762549 is associated with an
      interindividual difference in the plasma levels of MRP2 substrates, phase II
      metabolites of isoflavonoids, suggesting that this single nucleotide polymorphism
      is associated with variations in in-vivo MRP2 activity.

PMID- 22407409
TI  - PharmGKB summary:  very important pharmacogene information for CYP3A5.

PMID- 22407411
TI  - [Psychiatry and psychopathology of people with intellectual disability].

PMID- 22407410
TI  - Brain arteriovenous malformation diagnosis: value of time-resolved contrast
      enhanced MR angiography at 3.0T compared to DSA.
AB  - INTRODUCTION: This study was conducted in order to evaluate the value of time
      resolved contrast-enhanced magnetic resonance angiography (TR-CE-MRA) with a 3.0
      T magnetic field compared to digital subtraction angiography (DSA) as the
      reference standard for the diagnosis of brain arteriovenous malformation (bAVM).
      METHODS: Nineteen patients with 19 angiographically confirmed untreated bAVM were
      investigated with both DSA and TR-CE-MRA for the initial diagnosis. Examinations
      were compared by two independent readers. Interobserver agreement and
      intermodality agreement with respect to nidus size, arterial feeders, and venous
      drainage were determined using the K statistic test. Also, the quality of the TR
      CE-MRA images was evaluated. RESULTS: Seventeen of the 19 bAVM (89.5%) detected
      with DSA were diagnosed with TR-CE-MRA. Interobserver agreement for TR-CE-MRA was
      good for nidus size, venous drainage, and arterial feeders (K = 0.75, 95% CI 0.50
      1.00; K = 0.77, 95% CI 0.54-1.00; and K = 0.80, 95% CI 0.59-1.00 respectively).
      Intermodality agreement was good for nidus size and venous drainage (K = 0.75,
      95% CI 0.49-1.00 and K = 0.77, 95% CI 0.54-1.00, respectively) and moderate for
      arterial feeders (K = 0.44, 95% CI 0.17-0.70). CONCLUSION: TR-CE-MRA at 3.0 T has
      a good sensitivity for bAVM detection and good agreement with DSA for determining
      nidus size and the type of venous drainage, suggesting that TR-CE-MRA is
      potentially a reliable tool for the diagnosis and assessment of bAVMs. However,
      it still suffers from low spatial resolution and vessel superposition, making
      differentiation of the arterial feeders of the nidus difficult at times.

PMID- 22407412
TI  - [Mild cognitive impairment and depressive symptoms in patients with Wilson's
      disease under long-term therapy].
AB  - INTRODUCTION: Wilson's disease is a rare autosomal recessive disorder of hepatic
      copper transport leading to a biliary excretion inhibition of copper. Overloading
      of the metal mainly in the liver and basal ganglia leads not only to hepatic but
      also to extrapyramidal motor as well as psychiatric clinical symptoms. Cognitive
      dysfunction is often reported and patients suffer from additional depressive
      symptoms. METHODS: In this study, a cognitive impairment profile with SIDAM
      (SISCO) including mini-mental state, digit span and the trail making test was
      performed in 32 patients with Wilson's disease (24 patients with the neurological
      form, 8 patients with the non-neurological form) undergoing long-term
      medicamentous therapy. The extent of neurological impairment was assessed in a
      neurology score. The Beck depression inventory (BDI) was used for the detection
      of depressive symptoms. Results of cognitive testing and BDI score were
      correlated with the results of the clinical investigation. RESULTS: Median
      results of MMSE, SIDAM, part of digit span and trail-making test are
      significantly worse in patients with the neurological form of Wilson's disease.
      There is no significant difference in median results of BDI, although the number
      of patients with a score suggesting a mild depressive disorder is higher in the
      group with the neurological form. The median result of SIDAM was 52 (45-55) in
      the neurological form and 54 (53-55) points in the non-neurological form. There
      is no statistical significance in the correlation to the severity of the
      neurological score. CONCLUSIONS: Depressive symptoms and cognitive impairment in
      Wilson's disease are frequently reported by patients who are on long-term
      treatment. In particular, the ability to concentrate and undertake executive
      functions are affected in the neurological form of Wilson's disease while
      functions of memory are less impaired. Since movement disorders often have
      improved with therapy, additional observation of cognitive function and
      depressive disorders seems to be useful. However, mild cognitive impairment
      occurs independently of the severity of the neurological symptoms.

PMID- 22407413
TI  - [Botulinum toxin in clinical neurology].

PMID- 22407415
TI  - Intramural idiopathic ventricular arrhythmias originating in the intraventricular
      septum: mapping and ablation.
AB  - BACKGROUND: Intramural septal idiopathic ventricular arrhythmias have not been
      described systematically. METHODS AND RESULTS: In a consecutive group of 93
      patients with idiopathic ventricular arrhythmias referred for ablation, the site
      of origin of ventricular arrhythmias was assessed by activation mapping and pace
      mapping. In 7 of 93 patients (8%), an intramural focus in the interventricular
      septum was identified. All ventricular arrhythmias arising intramurally had a
      left bundle-branch block morphology with inferior axis. The intramural focus was
      effectively ablated from both sides of the septum in 4 patients and from within
      the septum in 1 patient. The ablation procedure of an intramural focus near the
      His bundle failed in 2 of 7 patients. ECG and mapping characteristics of the
      patients with intramural septal ventricular arrhythmias differentiated intramural
      arrhythmias from other sites of origin. CONCLUSIONS: Idiopathic septal
      ventricular arrhythmias can originate from intramural foci. Activation mapping
      from within a perforator branch within the interventricular septum is helpful in
      identifying the site of origin of intramural septal arrhythmias. Ablation within
      the septum or from both sites of the septum may be required to eliminate the
      targeted arrhythmia.

PMID- 22407414
TI  - Electrophysiological characteristics of canine superior vena cava sleeve
      preparations: effect of ranolazine.
AB  - BACKGROUND: In addition to extrasystoles of pulmonary vein (PV) origin, those
      arising from the superior vena cava (SVC) can precipitate atrial fibrillation
      (AF). The present study evaluates the electrophysiological properties of canine
      SVC sleeve preparations and the effect of ranolazine on late phase 3 early and
      delayed afterdepolarization (EAD and DAD)-induced triggered activity in SVC
      sleeves and compares SVC and PV sleeve electrophysiological properties. METHODS
      AND RESULTS: Action potentials (APs) were recorded from superfused SVC and PV
      sleeves using microelectrode techniques. Acetylcholine (1 MUmol/L), isoproterenol
      (1 MUmol/L), high calcium ([Ca(2+)](o)=5.4 mmol/L), or a combination were used to
      induce EADs, DADs, and triggered activity. A marked diversity of action potential
      characteristics was observed in the SVC sleeve, including action potentials with
      short and long APs, with and without phase 4 depolarization. Rapid pacing induced
      hyperpolarization, accentuating the slope of phase 4 depolarization. Phase 4
      depolarization and rapid pacing-induced hyperpolarization were reduced or
      eliminated after atropine (10 MUmol/L) or ranolazine (10 MUmol/L). APs displaying
      phase 4 depolarization (n=19) had longer APDs, smaller amplitude and V(max), and
      a more positive take-off potential than APs lacking phase 4 depolarization
      (n=15). Ranolazine (5-10 MUmol/L) eliminated late phase 3 EAD- and DAD-induced
      triggered activity as well as isoproterenol-induced automaticity elicited in SVC
      sleeves. Compared with PV, SVC sleeves display phase 4 depolarization, smaller
      V(max), and longer APs. CONCLUSIONS: Autonomic influences promote spontaneous
      automaticity and triggered activity in SVC sleeves, thus generating extrasystolic
      activity capable of initiating atrial arrhythmias. Ranolazine can effectively
      suppress these triggers.

PMID- 22407416
TI  - Adsorptive removal of toxic azo dye Amido Black 10B by hen feather.
AB  - PURPOSE AND AIM: Amido Black 10B is an azo dye with very high toxicity. It is now
      established that the dye damages the reparatory system of humans and also causes
      skin and eye irritations. It is therefore considered worthwhile to develop a
      systematic procedure to eradicate Amido Black 10B from its aqueous solution using
      a waste material as adsorbent. Therefore, adsorption of the dye is achieved using
      hen feathers as adsorbent. MATERIALS AND METHODS: Before using hen feather as
      adsorbent material, it is washed, cut into small pieces and activated using
      hydrogen peroxide. Detailed chemical and physical analysis of hen feather was
      also carried out by known analytical techniques. The adsorptive removal of the
      dye was made through batch experiments in 100 mL airtight flasks. The experiment
      is divided in three major categories, the preliminary investigations, adsorption
      isotherm measurements, and kinetic studies. RESULTS: Under preliminary
      investigations, the effect of pH, temperature, concentration of dye, and amount
      of adsorbent were carried out. It was found that with increase in pH, the
      adsorption of Amido Black 10B decreases; while with increasing the amount of hen
      feather, it increases. The isothermal studies indicate that the ongoing
      adsorption process is endothermic in nature and obeys Langmuir, Freundlich,
      Tempkin, and Dubinin-Radushkevitch (D-R) adsorption isotherm models. The Gibb's
      free energy and entropy of the adsorption were also calculated. The D-R isotherm
      model verified the involvement of chemisorption during the adsorption. The
      kinetic measurements indicate operation of pseudo second order process during the
      adsorption and dominance of film diffusion mechanism at all the temperatures.
      CONCLUSIONS: The developed method is highly efficient and ecofriendly. It also
      ascertains a necessitous utilization of waste material hen feather for the
      benefit of the society.

PMID- 22407418
TI  - Mathematical modeling of metabolism and hemodynamics.
AB  - We provide a mathematical study of a model of energy metabolism and hemodynamics
      of glioma allowing a better understanding of metabolic modifications leading to
      anaplastic transformation from low grade glioma. This mathematical analysis
      allows ultimately to unveil the solution to a viability problem which seems quite
      pertinent for applications to medecine.

PMID- 22407417
TI  - The effects of cerium on the growth and some antioxidant metabolisms in rice
      seedlings.
AB  - INTRODUCTION: The aims of the present study are to investigate the effects of
      Ce(3+) on the growth and some antioxidant metabolisms in rice seedlings (Oryza
      sativa L. cv Shengdao 16). MATERIALS AND METHODS: The rice was treated with 0,
      0.05, 0.1, 0.5, 1.0, and 1.5 mM Ce(3+), respectively. The growth index of rice
      was measured. The chlorophyll content; catalase, superoxide dismutase, and
      peroxidase activities; and the level of hydrogen peroxide (H(2)O(2)), superoxide
      anion (O (2) (.-) ), and malondialdehyde were assayed. The accumulation of Ce(3+)
      and the uptake of mineral nutrition elements were analyzed with ICP-SF-MS.
      RESULTS AND DISCUSSION: Hormetic effects of Ce(3+) on the growth and some
      antioxidant metabolisms were found in the roots and shoots of rice. The roots can
      accumulate a much higher content of Ce(3+) than shoots and Ce(3+) mainly located
      in the cell wall of roots. Moreover, the uptake of K, Mg, Ca, Na, Fe, Mn, Zn, Cu,
      and Mo in the roots and shoots was affected with the exposure of different Ce(3+)
      treatments, which indicated that Ce(3+) affected the nutritional status of roots
      and shoots and further affected the growth of rice. CONCLUSION: The appropriate
      amount of Ce(3+) improved the defense system and growth of rice. The roots can
      accumulate a much higher content of Ce(3+) than shoots. Moreover, the uptake of
      K, Mg, Ca, Na, Fe, Mn, Zn, Cu, and Mo in the roots and shoots was affected with
      the exposure of different Ce(3+) treatments.

PMID- 22407419
TI  - Aerosol-derived Ni(1-x)Zn(x) electrocatalysts for direct hydrazine fuel cells.
AB  - This article reports the synthesis and performance of unsupported Ni(1-x)Zn(x)
      electrocatalysts for the oxidation of hydrazine in alkaline media.
      Characterization of these catalysts was achieved using XRD, SEM, and TEM to
      confirm phase compositions, crystal structures, and morphologies. High
      performance was observed for the alpha-Ni(0.87)Zn(0.13) and beta(1)
      Ni(0.50)Zn(0.50) electrocatalysts with an onset potential of -0.15 V (vs. RHE)
      and a mass activity of 4000-3800 A g(cat)(-1) at 0.4 V (vs. RHE), respectively.
      Additionally, in situ IRRAS studies were conducted to understand the mechanism of
      oxidation. These results demonstrate the feasibility of Ni(1-x)Zn(x) catalysts
      for direct hydrazine anionic fuel cells.

PMID- 22407420
TI  - Pulmonary arteriovenous fistula coexisting with secundum atrial septal defect. An
      unusual cause of stroke in a young woman.
AB  - Pulmonary arteriovenous malformations (PAVM) consist of an abnormal connection
      between the pulmonary artery and vein bypassing the pulmonary capillary bed.
      Pulmonary arteriovenous fistulae are characterized by a right-to-left shunt of
      variable magnitude, and they may be accompanied by other congenital anomalies. We
      describe a case of pulmonary arteriovenous fistula with a secundum type atrial
      septal defect (ASD) in a 38-year-old woman, who underwent successful
      transcatheter closure of both the ASD and PAVM.

PMID- 22407421
TI  - Left main coronary artery aneurysm.
AB  - Left main coronary artery aneurysms (LMCA) are usually asymptomatic and are
      rarely encountered during coronary angiography. The most serious complications
      include coronary thrombosis, acute myocardial infarction and sudden death.
      Atherosclerosis is the most common cause, although several autoimmune diseases
      and congenital abnormalities have been associated with the presence of coronary
      aneurysms. The case of a symptom-free 63-year-old man with a giant LMCA and
      severely ectatic coronary arteries is presented.

PMID- 22407422
TI  - Vasospastic angina in a patient with hyperthyroidism.
AB  - A 56-year-old man presented with typical angina pectoris lasting >20 min
      associated with precordial ST-segment elevation. Urgent coronary angiography
      showed critical stenosis in the proximal segment of the left anterior descending
      artery, which resolved with intracoronary nitrate application. He was
      subsequently diagnosed with hyperthyroidism secondary to exposure of iodinated
      contrast agent which is thought to be the cause of the coronary spasm. Symptoms
      resolved upon treatment with propylthiouracil, slow-release diltiazem, isosorbide
      mononitrate, and aspirin. This unusual case highlights the importance of
      considering hyperthyroidism in the differential diagnosis of chest pain and
      coronary artery spasm. We suggest routine thyroid function testing in patients
      with coronary spasm.

PMID- 22407423
TI  - Severe limb pain suppresses chest pain in a patient with anterior myocardial
      infarction.
AB  - Cardiac complications of chest trauma range from arrhythmias and valvular
      avulsions to myocardial contusion, rupture, and--rarely--myocardial infarction.
      Herein, we described a 44-year-old male patient who presented to the hospital
      after receiving a blow from a fist directly to the chest and fingertip amputation
      during a fight; anterior myocardial infarction without any chest pain was
      coincidentally detected. Our case illustrates the importance of
      electrocardiography in the initial evaluation of patients with chest trauma and
      suspected injury to the coronary arteries.

PMID- 22407424
TI  - Huge mediastinal mass surrounding the heart.
AB  - The clinical presentation of oncological malignancies may vary widely. Herein, we
      present a patient with a huge mediastinal mass surrounding the heart, which
      caused the right ventricle to collapse. The mass was diagnosed as T-cell
      lymphoblastic lymphoma. Treatment consisted of intrathecal prednisone, ARA-C,
      methotrexate, and the CHOP chemotherapy regimen. Transthoracic echocardiography
      revealed disappearance of the paracardiac mass in front of the right ventricle at
      the 2-month follow-up.

PMID- 22407425
TI  - Bypass surgery versus percutaneous coronary intervention for the treatment of
      unprotected left main disease. A meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: We performed a meta-analysis of randomized controlled trials to
      compare coronary artery bypass grafting (CABG) and percutaneous coronary
      intervention (PCI) for the treatment of de novo unprotected left main disease.
      BACKGROUND: Although CABG is accepted to be standard of care for
      revascularization of unprotected left main stenosis, PCI is increasingly being
      used as an alternative primary approach. METHODS: We searched for randomized,
      controlled trials comparing CABG and PCI for the treatment of unprotected left
      main disease. Major adverse cardiac and cerebrovascular events (all-cause death,
      myocardial infarction, stroke, and repeat revascularization) were analyzed.
      RESULTS: The search strategy identified 4 randomized controlled trials enrolling
      a total of 1,611 patients. Follow-up ranged between 1 and 2 years. There were no
      significant differences in the risk of death or myocardial infarction between the
      two treatment modalities. While the risk of stroke was significantly lower in
      patients undergoing PCI (risk ratio (RR) 0.26, 95% confidence interval (CI) 0.10
      0.69, p = 0.007), the risk of repeat revascularization was higher among patients
      undergoing PCI (RR 1.94, 95% CI 1.43-2.61, p < 0.001). No relevant statistical
      heterogeneity across studies could be found. CONCLUSION: In this largest series
      of randomized patients with unprotected left main stenosis to date, the risk of
      death and myocardial infarction was comparable between CABG and PCI. However,
      patients undergoing CABG had a higher risk of stroke, whereas patients undergoing
      PCI were at a higher risk for repeat revascularization.

PMID- 22407426
TI  - Patient management after noninvasive cardiac imaging: a commentary on the
      reported results from SPARC.

PMID- 22407427
TI  - Dynamic analysis of epidermal cell divisions identifies specific roles for COP10
      in Arabidopsis stomatal lineage development.
AB  - Stomatal development in Arabidopsis thaliana has been linked to photoreceptor
      perceived light through several components of the photomorphogenic switch, whose
      lack of function is often seedling-lethal. CONSTITUTIVE PHOTOMORPHOGENIC 10
      (COP10) is an important component of this switch, its loss of function producing
      stomatal clusters. Exploiting the reduced lethality of the cop10-1 mutant we
      characterized the developmental basis of its stomatal phenotype. Constitutive,
      light-independent stomata overproduction accounts for half of cop10-1 stomatal
      abundance and appears very early in development. Clusters are responsible for the
      remaining stomata excess and build-up progressively at later stages. Serial
      impressions of living cotyledon epidermis allowed a dynamic, quantitative
      analysis of stomatal lineage types by reconstructing their division histories. We
      found that COP10 adjusts the initiation frequency and extension of stomatal
      lineages (entry and amplifying asymmetric divisions) and represses stomatal fate
      in lineage cells; COP10 also supervises the orientation of spacing divisions in
      satellite lineages, preventing the appearance of stomata in contact. Aberrant
      accumulation of the proliferating stomatal lineage cell marker TMMpro::TMM-GFP
      showed that the abundant cop10-1 stomatal lineages maintained extended and
      ectopic competence for stomatal fate. Expression of stomatal development master
      genes suggests that the mutant does not bypass major molecular actors in this
      process. cop10-1 first leaf produces trichomes and apparently normal pavement
      cells, but functionally and morphologically aberrant stomata; COP10 operates
      genetically in parallel to the stomatal repressor SDD1 and does not generally
      affect epidermal cell differentiation, but seems to operate on stomatal lineages
      where it controls specific cell-lineage and cell-signaling developmental
      mechanisms.

PMID- 22407428
TI  - Therapeutic regimen options for isolated superior mesenteric artery dissection.
AB  - OBJECTIVE: To summarize the reproducible experience obtained during the treatment
      of superior mesenteric artery dissection (SMAD) and to investigate the
      therapeutic options for this condition. METHODS: The clinical data from 10
      patients with SMAD were retrospectively analyzed, including 6 patients receiving
      conservative therapy, 2 patients receiving endovascular stenting, 1 patient
      receiving dissecting aneurysm resection plus vascular prosthesis grafting, and 1
      patient receiving thrombectomy plus intimectomy. RESULTS: For the 6 patients
      subjected to the conservative therapy, the symptoms were thoroughly under control
      without relapse during the follow-up; for the 2 patients receiving endovascular
      stenting, the computed tomography (CT) examination performed during the follow-up
      demonstrated a patent true lumen and an occluded false lumen; for the patient
      with dissecting aneurysm resection plus vascular prosthesis grafting, a short
      dissection was observed at the distal end of the vascular prosthesis but without
      progression during the 14-month follow-up period; for the patient with
      thrombectomy plus intimectomy, postoperatively, the patient experienced diarrhea,
      body weight loss, and hypoproteinemia, and CT scanning demonstrated segmental SMA
      occlusions, which were not fully remitted by conservative therapy until the
      application of endovascular stenting 4 months later. CONCLUSIONS: The therapeutic
      regimen for isolated SMAD should be established based on the clinical symptoms of
      the patient and the hemodynamic status in SMA. The conservative therapy is mainly
      indicated for the asymptomatic patients or those with short-term symptoms, while
      the endovascular or surgical therapy should be recommended for those with
      persistent intestinal ischemia-related symptoms, rupture of artery, and/or
      obvious aneurysmal false lumen dilation at a high risk of rupture.

PMID- 22407429
TI  - Preoperative cardiac evaluation of the vascular surgery patient--an anesthesia
      perspective.
AB  - The morbidity and mortality associated with vascular surgery procedures are
      largely the results of cardiac events. National guidelines have been regularly
      proposed and updated by the American College of Cardiology (ACC)/American Heart
      Association (AHA) to ensure optimal perioperative management and risk
      stratification. Controversy remains between experts and other cardiology
      societies regarding several patient care issues including revascularization
      before surgery, timing of beta-blocker therapy, and the administration of
      antiplatelet therapy. Several landmark articles recently published have helped to
      modify the guidelines in the hope of improving vascular patient outcomes. In this
      review, we searched all recent available literature pertaining to perioperative
      cardiac evaluation before major vascular surgery. We propose an algorithm for
      preoperative cardiac evaluation, which is a modification to the AHA
      recommendations. Incorporated in this algorithm are recent published pivotal
      articles that can help in guiding physicians caring for the vascular patient
      requiring major operative or endovascular interventions.

PMID- 22407430
TI  - Consistency between cross-sectional and longitudinal SNP: blood lipid
      associations.
AB  - Various studies have linked different genetic single nucleotide polymorphisms
      (SNPs) to different blood lipids (BL), but whether these "connections" were
      identified using cross-sectional or longitudinal (i.e., changes over time)
      designs has received little attention. Cross-sectional and longitudinal
      assessments of BL [total, high-, low-density lipoprotein cholesterol (TC, HDL,
      LDL), triglycerides (TG)] and non-genetic factors (body mass index, smoking,
      alcohol intake) were measured for 2,002 Geneva, Switzerland, adults during 1999
      2008 (two measurements, median 6 years apart), and 20 SNPs in 13 BL metabolism
      related genes. Fixed and mixed effects repeated measures linear regression
      models, respectively, were employed to identify cross-sectional and longitudinal
      SNP:BL associations among the 1,516 (76%) study participants who reported not
      being treated for hypercholesterolemia at either measurement time. One-third more
      (12 vs. 9) longitudinal than cross-sectional associations were found [Bonferroni
      adjusted two-tailed p < 0.00125 (=0.05/2)/20) for each of the four ensembles of
      20 SNP:individual BL associations tested under the two study designs]. There was
      moderate consistency between the cross-sectional and longitudinal findings, with
      eight SNP:BL associations consistently identified across both study designs:
      [APOE.2 and APOE.4 (rs7412 and rs429358)]:TC; HL/LIPC (rs2070895):HDL; [APOB
      (rs1367117), APOE.2 and APOE.4 (rs7412 and rs429358)]:LDL; [APOA5 (rs2072560) and
      APOC III (rs5128)]:TG. The results suggest that cross-sectional studies, which
      include most genome-wide association studies (GWAS), can assess the large
      majority of SNP:BL associations. In the present analysis, which was much less
      powered than a GWAS, the cross-sectional study was around 2/3 (67%) as efficient
      as the longitudinal study.

PMID- 22407432
TI  - Determination of naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) in mouse
      blood and tissue after inhalation exposure to 'buzz' smoke by HPLC/MS/MS.
AB  - The disposition of the cannabimimetic naphthalen-1-yl-(1-pentylindol-3
      yl)methanone (JWH-018) in mice following inhalation of the smoke of the herbal
      incense product (HIP) 'Buzz' is presented. A high-pressure liquid chromatography
      with electrospray ionization triple quadrupole mass spectrometer (HPLC/MS/MS)
      method was validated for the analysis of JWH-018 in the specimens using
      deuterated Delta(9) -tetrahydrocannabinol (d(3) -THC) as the internal standard.
      JWH-018 was isolated by cold acetonitrile liquid-liquid extraction.
      Chromatographic separation was performed on a Zorbaz eclipse XDB-C(18) column.
      The assay was linear from 1 to 1000 ng/mL. Six C57BL6 mice were sacrificed 20 min
      after exposure to the smoke of 200 mg 'Buzz' containing 5.4% JWH-018. Specimen
      concentrations of JWH-018 were: blood, 54-166 ng/mL (mean 82 +/- 42 ng/mL);
      brain, 316-708 ng/g (mean 510 +/- 166 ng/g); and liver, 1370-3220 ng/mL (mean
      1990 +/- 752 ng/mL). The mean blood to brain ratio for JWH-018 was 6.8 and ranged
      from 4.2 to 10.9. After exposure, the responses of the mice were consistent with
      cannabinoid receptor type 1 activity: body temperatures dropped 7.3 +/- 1.1 
      degrees C, and catalepsy, hyperreflexia, straub tail and ptosis were observed.
      The brain concentrations and physiological responses are consistent with the
      hypothesis that the behavioral effects of 'Buzz' are attributable to JWH-018.

PMID- 22407433
TI  - Kruppel-like factor 4 negatively regulates beta-catenin expression and inhibits
      the proliferation, invasion and metastasis of gastric cancer.
AB  - Kruppel-like factor 4 (KLF4) is a zinc-finger protein that plays an important
      role in the progression of gastric carcinoma. The abnormal activation of beta
      catenin frequently occurs in gastric cancer and has been associated with the
      promotion of tumor growth, invasion and metastasis. However, the potential
      interaction between KLF4 and beta-catenin during gastric cancer development is
      unknown. In this study, a lentiviral KLF4 expression vector was constructed and
      utilized to transfect the human gastric cancer cell lines, SGC-7901, BGC-823, MKN
      28 and MKN-45. KLF4 and beta-catenin expression levels were measured by
      quantitative real-time RT-PCR and western blot analysis. Cell proliferation,
      colony formation and invasive potential were determined in the KLF4-transfected
      gastric cancer cells. The expression of E-cadherin and matrix metallopeptidase 2
      (MMP2) was determined by western blot analysis. The overexpression of KLF4
      significantly inhibited the expression of beta-catenin in the MKN-45 gastric
      cancer cells. The restored expression of KLF4 suppressed proliferation, colony
      formation and inhibited the invasion and metastatic properties of MKN-45 gastric
      cancer cells. Furthermore, the forced expression of KLF4 in gastric tumor cell
      lines restored E-cadherin expression and inhibited MMP2 expression. Consistent
      with the in vitro findings, the enforced expression of the KLF4 gene in MKN-45
      gastric carcinoma cells by lentiviral vector-mediated gene transfer effectively
      suppressed tumor growth in vivo. Our results show that KLF4 inhibits beta-catenin
      expression and regulates the beta-catenin-mediated biological behaviors of
      gastric cancer cells. The modulation of KLF4 expression may represent a novel
      therapeutic approach for beta-catenin-driven malignancies.

PMID- 22407434
TI  - Deceleration of arginine kinase refolding by induced helical structures.
AB  - Arginine kinase (AK) is a key metabolic enzyme for keeping energy balance in
      invertebrates. Therefore, regulation of the enzymatic activity and the folding
      studies of AK from the various invertebrates have been the focus of
      investigation. We studied the effects of helical structures by using
      hexafluoroisopropanol (HFIP) on AK folding. Folding kinetic studies showed that
      the folding rates of the urea-denatured AKs were significantly decelerated after
      being induced in various concentrations of HFIP. AK lost its activity completely
      at concentrations greater than 60%. The results indicated that the HFIP-induced
      helical structures in the denatured state play a negative role in protein
      folding, and the helical structures induced in 5% (v/v) HFIP act as the most
      effective barrier against AK taking its native structure. The computational
      docking simulations (binding energies for -2.19 kcal/mol for AutoDock4.2 and 
      20.47 kcal/mol for Dock6.3) suggested that HFIP interacts with the several
      important residues that are predicted by both programs. The excessively pre
      organized helical structures not only hampered the folding process, but also
      ultimately brought about changes in the three-dimensional conformation and
      biological function of AK.

PMID- 22407435
TI  - Selective forces for the origin of spliceosomes.
AB  - It has been proposed that eukaryotic spliceosomes evolved from bacterial group II
      introns via constructive neutral changes. However, a more likely interpretation
      is that spliceosomes and group II introns share a common undefined RNA ancestor-
      a proto-spliceosome. Although, the constructive neutral evolution may have
      probably played some roles in the development of complexity including the
      evolution of modern spliceosomes, in fact, the origin, losses and the retention
      of spliceosomes can be explained straight-forwardly mainly by positive and
      negative selection: (1) proto-spliceosomes evolved in the RNA world as a
      mechanism to excise functional RNAs from an RNA genome and to join non-coding
      information (ancestral to exons) possibly designed to be degraded. (2) The
      complexity of proto-spliceosomes increased with the invention of protein
      synthesis in the RNP world and they were adopted for (a) the addition of
      translation signal to RNAs via trans-splicing, and for (b) the exon-shuffling
      such as to join together exons coding separate protein domains, to translate them
      as a single unit and thus to facilitate the molecular interaction of protein
      domains needed to be assembled to functional catalytic complexes. (3) Finally,
      the spliceosomes were adopted for cis-splicing of (mainly) non-coding information
      (contemporary introns) to yield translatable mRNAs. (4) Spliceosome-negative
      organisms (i.e., prokaryotes) have been selected in the DNA-protein world to save
      a lot of energy. (5) Spliceosome-positive organisms (i.e., eukaryotes) have been
      selected, because they have been completely spliceosome-dependent.

PMID- 22407436
TI  - Blocking of beta-adrenergic receptors during the subfertile period inhibits
      spontaneous ovarian cyst formation in rats.
AB  - As aging proceeds, fertility problems arise, and the success rate of in vitro
      fertilization declines. During reproductive aging, rat ovaries present
      spontaneous formation of cysts, followed by a concomitant increase in sympathetic
      nerve activity, causing infertility and cessation of ovarian function. beta2
      Adrenergic receptors, which are activated by noradrenaline (NA), modify
      follicular development and steroid secretions; thus, increased nerve activity has
      been associated with the development and maintenance of cystic structures. The
      purpose of this work was to block the effect of this sympathetic activity through
      in vivo administration of propranolol (a beta-adrenergic receptor antagonist) to
      determine whether it delays cyst formation and cessation of the ovarian function
      in rats that had reached the subfertile period. Propranolol was administrated
      daily to 8- and 10-month-old rats for 2 months. Estrous cycling activity was
      monitored by vaginal smear, serum concentration of the steroidal hormones was
      determined by enzyme-immune assay and morphological analysis of the ovaries was
      performed using 6 MUm tissue slices stained with hematoxylin-eosin. Propranolol
      increased the number of healthy follicles, the ovulation rate, and levels of
      serum sexual steroids (androstenedione, testosterone, and estradiol) and
      recovered estrous cycling activity. It also decreased the number of follicular
      cysts. These results suggest that the blockade of beta-adrenergic receptors
      recovered ovarian function during reproductive aging. It is suggested that
      propranolol induces a time-dependent extension of the subfertile window, and it
      could be used to increase the success rate of fertility programs in aging woman.

PMID- 22407437
TI  - Feasibility of semi-quantitative assessment of left ventricular contractile
      reserve in dilated cardiomyopathy.
AB  - BACKGROUND: We and others have shown previously that left ventricular (LV)
      contractile reserve assessed quantitatively by high-dose dobutamine stress
      echocardiography (DSE) has prognostic implications in patients with dilated
      cardiomyopathy. PURPOSE: To assess the feasibility of semi-quantitative
      assessment of LV contractile reserve by differently skilled operators in patients
      with dilated cardiomyopathy. METHODS: High-dose DSE was performed in 63
      consecutive patients, mean age 50 +/- 10 years and ejection fraction (EF) 19 +/-
      8%. LVEF was calculated 1) using Simpson's biplane formula, and 2) semi
      quantitatively (5% increments) by novice and experienced echocardiographers, and
      by a DSE expert. Patients were considered to have preserved LV contractile
      reserve if LVEF dobutamine-induced change was >=5%. RESULTS: Twenty-seven (45.8%)
      patients died during the 5-year follow-up. The feasibility of the assessment was
      89%, 94%, and 98% for novice and experienced readers and DSE expert,
      respectively. Kaplan-Meier analysis showed that LV contractile reserve assessed
      semi-quantitatively by DSE expert and experienced reader achieved the best
      prognostic separation (log rank 19.63 and 18.99, respectively, p < 0.001 for
      both), followed by quantitative assessment (log rank 9.76, p = 0.0018) and
      assessment by novice reader (log rank 8.76, p = 0.012). Areas under the curves
      were similar for quantitative and semi-quantitative assessment of LV contractile
      reserve. CONCLUSIONS: Our data indicate that semi-quantitative assessment of LV
      contractile reserve is feasible by differently skilled operators.

PMID- 22407438
TI  - Recruitment and retention in an adolescent anorexia nervosa treatment trial.
AB  - OBJECTIVE: To investigate recruitment and retention for a randomized controlled
      trial (RCT) of adolescent anorexia nervosa (AN), as prior studies suggest that
      these are significant hurdles to completing meaningful RCTs in this population.
      METHOD: Retrospective analyses of recruitment and retention rates were conducted
      for a multisite RCT of family-based treatment (FBT) versus adolescent-focused
      therapy (AFT) recruiting adolescents between 12 and 18 years of age with AN.
      RESULTS: Adolescent participants were recruited from a variety of both medical
      and nonmedical sources. Recruitment goals were met in time (October 2004-March
      2007). Percent retention rates were high across both treatment types (84% for FBT
      and 92% for AFT), and these rates did not differ significantly. DISCUSSION: These
      results reveal that recruitment and retention of adolescent patients with AN to
      RCTs are feasible in contrast to the experience in adult studies. It is likely
      that characteristics of our clinical programs make recruitment easier than in
      other settings, e.g., child and adolescent focused, specialized eating disorders
      program with an emphasis on outpatient treatment, recognized leaders in the
      field, and a history of clinical excellence with this population.

PMID- 22407440
TI  - Antioxidative flavonol glycosides from the flowers of Abelmouschus manihot.
AB  - Bioassay-guided fractionation led to the isolation of six new flavonol
      glycosides, floramanosides A (1), B (2), C (3), D (4), E (5), and F (6), from the
      flowers of Abelmouschus manihot. Their structures were elucidated by chemical and
      spectroscopic methods (UV, IR, HRESI-TOF-MS, 1D- and 2D-NMR). Activity screening
      results showed that the compounds had 2,2-diphenyl-1-picrylhydrazyl scavenging
      and aldose reductase inhibitory activities.

PMID- 22407441
TI  - A rapid lactate dehydrogenase histochemical method for the intraoperative
      assessment of Hirschsprung's disease.
AB  - PURPOSE: The aim was to assess the ability of a fast lactate dehydrogenase (LDH)
      staining technique to evaluate the boundary of the abnormal bowel segment in
      Hirschsprung's disease (HD) as a guide for surgical resection. METHODS: Seventy
      children diagnosed with HD were equally divided into two groups. For the study
      group, fast LDH staining was used to confirm the diagnosis and determine the
      boundary of abnormal bowel. Frozen H&E staining was applied to the control group.
      Postoperatively, bowel samples were examined by paraffin H&E staining to confirm
      the intraoperative diagnosis. Patients received a follow-up analysis, and bowel
      function was scored and compared between the two groups. RESULTS: In the study
      group, 19 children were diagnosed with isolated HD, and the remaining had HD in
      combination with HD-allied disorders (HAD). The diagnosis was identical to the
      post-operative H&E staining, and the ganglia cells at the proximal end of the
      resected bowel were normal. In the control group, 30 children were diagnosed with
      isolated HD. However, the paraffin H&E staining showed that only 16 cases had
      isolated HD, and the remaining had a combined diagnosis of HAD. Moreover, 12 of
      these allied disorders were found at the proximal end of the resected bowel.
      Patients received follow-up for 6-15 months. The bowel function score of the
      study group was significantly higher than the control group. CONCLUSIONS: Fast
      LDH staining can clearly identify ganglion cells and rapidly diagnose HD and HAD
      intraoperatively. In addition, this method is helpful for improving patient
      prognosis.

PMID- 22407442
TI  - Endoscopic evaluation of the colon after an episode of diverticulitis: a call for
      a more selective approach.
AB  - PURPOSE: Routine colonic evaluation is advised after an episode of diverticulitis
      to exclude colorectal cancer. In the recent years, the possible relation between
      diverticulitis and colorectal cancer has been subject of debate. The aim of this
      study is to evaluate the benefit of routine colonic endoscopy after an episode of
      diverticulitis. METHODS: Records of all consecutive patients presenting with a
      radiologically confirmed episode of diverticulitis between 2007 and 2010 were
      retrieved from an in-hospital database. Patients who subsequently underwent
      colonic evaluation were included. The endoscopic detection rate of hyperplastic
      polyps, adenomas and advanced colonic neoplasia was assessed. Findings were
      categorized on the basis of the most advanced lesion identified. RESULTS: Three
      hundred and seven patients presented with a radiologically confirmed primary
      episode of diverticulitis. Two hundred and five patients underwent colonic
      evaluation. Hyperplastic polyps were found in15 (6.8 %), adenomas in 18 (8.8 %)
      and advanced neoplastic lesions in 7 (3.4 %) patients. Only two patients had a
      colorectal malignancy. CONCLUSION: There appears to be no benefit in performing
      routine colonic evaluation after an episode of diverticulitis as the incidence of
      colorectal cancer is almost equal to that of the general population. A more
      selective approach might therefore be justified. Potentially, only patients with
      persisting abdominal complaints after an episode of diverticulitis should be
      offered colonic evaluation to definitively exclude causal pathology.

PMID- 22407443
TI  - Life-threatening severe anaphylactic reactions in patients receiving oxaliplatin
      chemotherapy.

PMID- 22407444
TI  - Dysregulation of the beta3 integrin-VEGFR2 complex in Hantaan virus-directed
      hyperpermeability upon treatment with VEGF.
AB  - Hantaviruses infect human endothelial cells (ECs) and are known to cause vascular
      permeability-based diseases, including hemorrhagic fever with renal syndrome
      (HFRS) and hantavirus pulmonary syndrome (HPS). The alphavbeta3 integrins, which
      are highly expressed on the surface of ECs, serve as hantavirus receptors.
      Specifically, the beta3 integrin and vascular endothelial growth factor (VEGF)
      receptor 2 (VEGFR2) form a functional complex and interact with each other.
      Signaling through this complex causes cytoskeletal reorganization, which is one
      of the most important mechanisms underlying hyperpermeability. In this study, we
      show that VEGF dramatically enhances Hantaan virus (HTNV)-directed permeability
      and increases the reorganization of the cytoskeleton and the disruption of
      junctional organizations in an EC monolayer at 3 days postinfection. HTNV
      infection reduced the effect of VEGF on adhesion, migration, and the upregulation
      of beta3 expression, but the infection alone upregulated the expression of beta3
      and VEGFR2. These results indicate that in addition to its role in blocking beta3
      integrin activation as reported previously, HTNV blocks the function of the
      complex of VEGFR2 and beta3 integrin, and the dysfunction of the complex may
      contribute to cytoskeletal reorganization in an HTNV-directed hyperpermeability
      response to VEGF.

PMID- 22407445
TI  - Development and application of one-step multiplex reverse transcription PCR for
      simultaneous detection of five diarrheal viruses in adult cattle.
AB  - A one-step multiplex reverse transcription (RT)-PCR method was developed for the
      simultaneous detection of five viruses causing diarrhea in adult cattle: bovine
      group A rotavirus (GAR), bovine group B rotavirus (GBR), bovine group C rotavirus
      (GCR), bovine coronavirus (BCV), and bovine torovirus (BToV). The detection limit
      of the one-step multiplex RT-PCR for GAR, GCR, BCV, and BToV was 10(2), 10(0),
      10(1), and 10(2) TCID(50)/ml, respectively, and that for GBR was 10(6) copies/ml.
      The one-step multiplex RT-PCR with newly designed primers to detect GAR had
      higher sensitivity than a single RT-PCR with conventional primers, with no false
      positive reactions observed for ten other kinds of bovine RNA viruses To assess
      its field applicability, 59 of 60 fecal samples containing one of these five
      viruses from all 25 epidemic diarrhea outbreaks in adult cattle were positive in
      the one-step multiplex RT-PCR assay. Furthermore, using four additional fecal
      samples containing two viruses (GBR and BCV or BToV), two amplified products of
      the expected sizes were obtained simultaneously. In contrast, all 80 fecal
      samples lacking the five target viruses from normal adult cattle were negative in
      the multiplex assay. Taken together, our results indicate that the one-step
      multiplex RT-PCR developed here for the detection of GAR, GBR, GCR, BCV, and BToV
      can be expected to be a useful tool for the rapid and cost-effective diagnosis
      and surveillance of viral diarrhea in adult cattle.

PMID- 22407446
TI  - Urinary osteocalcin and serum pro-C-type natriuretic peptide predict linear catch
      up growth in infants.
AB  - Preterm (PT) infants are at risk of growth failure despite advanced early care
      and nutrition. In addition to poor weight gain, slow postnatal linear growth also
      is associated with adverse neurological outcome. Markers distinguishing infants
      at risk for impaired catch-up growth are needed. The aim of this longitudinal
      study was to determine the extent to which postnatal levels of circulating
      cartilage (serum pro-C-type natriuretic peptide [S-proCNP]) and urinary bone
      metabolic markers (urinary osteocalcin [MidOC] and two forms of C-terminal cross
      linked telopeptide of type I collagen [U-alpha-CTX-I and U-beta-CTX-I]) predict
      catch-up growth in infancy in 67 PT and 58 full-term (FT) infants. PT infants
      were significantly shorter than FT infants during the first 6 months of life, but
      no statistically significant difference was found at the corrected age of 14
      months (M14). At the age of 3 months (M3), S-ProCNP and U-MidOC levels, but not U
      alpha-CTX-I and U-beta-CTX-I levels, correlated positively with prospective
      growth velocity from M3 to M14 (rho = 0.460, p < 0.001 and rho = 0.710, p <
      0.001, respectively). In predicting slow linear growth (growth velocity at the
      lowest quartile), the area under the S-ProCNP ROC curve was 0.662 and that of U
      MidOC 0.891. Thus, U-MidOC, and to lesser extent S-ProCNP at M3 are predictors of
      catch-up growth in infancy.

PMID- 22407447
TI  - [Severe community-acquired and hospital-acquired pneumonia].
AB  - Severe community-acquired pneumonia and hospital-acquired pneumonia are common
      infectious diseases in Germany. They are associated with high mortality
      especially in the old and multimorbid patient and are thus a challenge in daily
      clinical practice. While the CRB65 is a thoroughly validated score for risk
      stratification in community-acquired pneumonia, there is no comparable score for
      hospital-acquired pneumonia yet. Early initiation of adequate antibiotic
      treatment is essential for a positive outcome. Hospital-acquired pneumonia is
      more often associated with multidrug-resistant bacteria, which should be
      considered in the choice of initial treatment especially if the patient can be
      considered a member of a risk group. This article focuses on severe pneumonia and
      gives an overview of the recent guidelines and discusses newly published results.

PMID- 22407448
TI  - Surgical pathology in sub-Saharan Africa--volunteering in Malawi.
AB  - The breadth of material found in surgical pathology services in African countries
      differs from the common spectrum of "the West". We report our experience of a
      voluntary work in the pathology departments of Blantyre and Lilongwe, Malawi.
      During a 6-week period, 405 cases (378 histology and 27 cytology cases) were
      processed. The vast majority showed significant pathological findings (n = 369;
      91.1 %): 175 cases (47.4 %) were non-tumoral conditions with predominance of
      inflammatory lesions, e.g., schistosomiasis (n = 11) and tuberculosis (n = 11).
      There were 39 (10.6 %) benign tumors or tumor-like lesions. Intraepithelial
      neoplasia of the cervix uteri dominated among premalignant conditions (n = 15;
      4.1 %). The large group of malignancies (n = 140; 37.9 %) comprised 11 pediatric
      tumors (e.g., rhabdomyosarcoma, small blue round cell tumors) and 129 adult
      tumors. Among women (n = 76), squamous cell carcinomas (SCCs) of the cervix uteri
      predominated (n = 25; 32.9 %), followed by breast carcinomas (n = 12; 15.8 %) and
      esophageal SCC (n = 9; 11.8 %). Males (n = 53) most often showed SCC of the
      esophagus (n = 9; 17.0 %) and of the urinary bladder (n = 7; 13.2 %). Lymphomas
      (n = 7) and Kaposi's sarcomas (n = 6) were less frequent. Differences compared to
      the western world include the character of the conditions in general, the
      spectrum of inflammatory lesions, and the young age of adult tumor patients
      (median 45 years; range 18-87 years). Providing pathology service in a low
      resource country may be handicapped by lack of personnel, inadequate material
      resources, or insufficient infrastructure. Rotating volunteers offer a bridge for
      capacity building of both personnel and the local medical service; in addition,
      the volunteer's horizons are broadened professionally and personally.

PMID- 22407450
TI  - Recent advances and applications of iridium-catalysed asymmetric allylic
      substitution.
AB  - Since their discovery in 1997, iridium-catalysed asymmetric allylic substitutions
      have been developed into a broadly applicable tool for the synthesis of chiral
      building blocks via C-C and C-heteroatom bond formation. The remarkable
      generality of these reactions and the high levels of regio- and
      enantioselectivity that are usually obtained in favour of the branched products
      have been made possible by a thorough investigation of the catalyst system and
      its mode of action. Therefore, today the Ir-catalysed asymmetric allylic
      substitution is a powerful reaction in the organic chemist's repertoire and has
      been used extensively for several applications. This article aims to provide an
      overview of the development of iridium catalysts derived from an Ir salt and a
      chiral phosphoramidite and their application to the enantioselective synthesis of
      natural products and biologically relevant compounds.

PMID- 22407449
TI  - Calpain-mediated vimentin cleavage occurs upstream of MT1-MMP membrane
      translocation to facilitate endothelial sprout initiation.
AB  - Endothelial cells normally line the vasculature and remain quiescent. However,
      these cells can be rapidly stimulated to undergo morphogenesis and initiate new
      blood vessel formation given the proper cues. This study reports a new mechanism
      for initiating angiogenic sprout formation that involves vimentin, the major
      intermediate filament protein in endothelial cells. Initial studies confirmed
      vimentin was required for sphingosine 1-phosphate (S1P)- and growth factor (GF)
      induced endothelial cell invasion, and vimentin was cleaved by calpains during
      invasion. Calpains were predominantly activated by GF and were required for
      sprout initiation. Because others have reported membrane type 1-matrix
      metalloproteinase (MT1-MMP) is required for endothelial sprouting responses, we
      tested whether vimentin and calpain acted upstream of MT1-MMP. Both calpain and
      vimentin were required for successful MT1-MMP membrane translocation, which was
      stimulated by S1P. In addition, vimentin complexed with MT1-MMP in a manner that
      required both the cytoplasmic domain of MT1-MMP and calpain activation, which
      increased the soluble pool of vimentin in endothelial cells. Altogether, these
      data indicate that pro-angiogenic signals converge to activate calpain-dependent
      vimentin cleavage and increase vimentin solubility, which act upstream to
      facilitate MT1-MMP membrane translocation, resulting in successful endothelial
      sprout formation in three-dimensional collagen matrices. These findings help
      explain why S1P and GF synergize to stimulate robust sprouting in 3D collagen
      matrices.

PMID- 22407451
TI  - Stroke treatment using intravenous and intra-arterial tissue plasminogen
      activator.
AB  - OPINION STATEMENT: Acute ischemic stroke is the most common cause of adult
      disability in the world and the third most common cause of death. Early
      restoration of perfusion to ischemic brain has been a highly successful strategy
      to decrease the disability associated with acute ischemic stroke. For acute
      stroke, intravenous (IV) tissue plasminogen activator (t-PA) is the only proven
      acute treatment that results in improved clinical outcomes. IV t-PA is indicated
      for ischemic stroke when administered within 4.5 h or less of symptom onset. This
      4.5-hour treatment window represents a significant expansion from the previous 3
      hour treatment window for therapy. Despite a longer time window, patients have
      the greatest chance for an improved outcome when treatment occurs as soon as
      possible from the time of symptom onset. The Emergency Department goal for
      treatment is a door to t-PA administration time of 60 min. In order to facilitate
      rapid evaluation and treatment, systems of care that streamline treatment should
      be developed at every institution that cares for acute ischemic stroke patients.
      For those with contraindications to t-PA and those outside the treatment window,
      catheter-directed intra-arterial (IA) t-PA administration or mechanical clot
      extraction is a potential means of restoring brain perfusion. These therapies
      should not preclude the use of IV t-PA when feasible and are frequently only
      available at tertiary care centers. Technological advances in IA devices for
      mechanical clot extraction make this a promising and growing area for advancing
      stroke therapy but remain under ongoing investigation to establish improved
      clinical outcomes.

PMID- 22407452
TI  - Medication adherence in Greek hemodialysis patients: the contribution of
      depression and health cognitions.
AB  - BACKGROUND: Several studies have shown that non-adherence is a common and
      increasing problem among individuals with chronic illnesses, including
      hemodialysis patients. PURPOSE: The present study aimed to investigate the
      influence of depression and health cognitions on medication adherence among
      patients undergoing hemodialysis. METHOD: A sample of 168 participants was
      recruited from six general hospitals in the broader area of Athens, consisting of
      patients undergoing in-center hemodialysis. Measurements were conducted with the
      following instruments: the Medication Adherence Rating Scale, the Center for
      Epidemiologic Studies Depression Scale (CES-D), and the Multidimensional Health
      Locus of Control (MHLC) scale. RESULTS: The results indicated that medication
      adherence was associated positively with the dimensions of internal and doctor
      attributed health locus of control, measured by the MHLC. It was also related
      negatively to depression, measured by the CES-D. CONCLUSIONS: The present study
      demonstrates the importance of depression in understanding the medication
      adherence of hemodialysis patients, as well as the contribution of heath
      cognitions.

PMID- 22407453
TI  - Familial effects on ischemic stroke: the role of sibling kinship, sex, and age of
      onset.
AB  - BACKGROUND: Previous studies on familial risk of ischemic stroke have supported
      genetic influence on the disease incidence. This study aimed to characterize
      these familial effects in a nationwide population-based study by taking into
      account sibling relations, sex of siblings, and age of onset, with respect to
      ischemic stroke incidence. METHODS AND RESULTS: Incident ischemic stroke cases
      identified from the Swedish Hospital Discharge and Cause of Death Registers
      between 1987 and 2007 were linked to their stroke-free siblings (study
      participants), forming an exposed sib-pair. Each exposed sib-pair was matched up
      to 5 unexposed sib-pairs from the Multi-Generation Registry by birth and calendar
      years. Incident ischemic stroke risk was assessed using hazard estimates obtained
      from stratified Cox regression analyses. A total of 30 735 exposed and 152 391
      unexposed study participants were included in the analyses. The overall risk of
      incident ischemic stroke when exposed was significantly increased (relative risk,
      1.61; 95% confidence interval, 1.48-1.75; P<0.001). Familial risk was higher in
      full (relative risk, 1.64; 95% confidence interval, 1.50-1.81; P<0.001) than in
      half (relative risk, 1.41; 95% confidence interval, 1.10-1.82; P=0.007) siblings.
      Familial risk of early ischemic stroke almost doubled when exposed to early
      ischemic stroke (relative risk, 1.94; 95% confidence interval, 1.41-2.67;
      P<0.001). CONCLUSIONS: There was a 60% increased risk for ischemic stroke in
      individuals having a sibling with prior stroke. The familial effect was even
      higher for full-sibling relations. Familial effects were observed in both male
      and female individuals, and no differential effects depending on the sex of
      either of the siblings were found.

PMID- 22407454
TI  - Desmosome-ion channel interactions and their possible role in arrhythmogenic
      cardiomyopathy.
AB  - Most commonly, arrhythmogenic cardiomyopathy (also known as arrhythmogenic right
      ventricular cardiomyopathy, or ARVC) is caused by mutations in desmosomal
      proteins. The question arises as to the mechanisms by which mutations in
      mechanical junctions, affect the rhythm of the heart. We have proposed that a
      component of the arrhythmogenic substrate may include changes in the function of
      both, gap junctions and sodium channels. Here, we review the relevant literature
      on this subject.

PMID- 22407455
TI  - Novel postoperative use of beta-blocking medication for infants with left
      ventricular outflow obstruction and diastolic myocardial dysfunction.
AB  - Severe left ventricular outflow obstruction often is associated with diastolic
      left ventricular myocardial dysfunction and tachycardia despite successful
      initial treatment. The authors have used esmolol to lower heart rate in this
      setting for successful weaning of patients from ventilation in postoperative
      recovery. Their limited experience supports the beneficial effect of continuous
      esmolol administration on infants with persistent tachycardia and severe left
      ventricular diastolic dysfunction in postoperative cardiac intensive care.

PMID- 22407456
TI  - Late surgical removal of an embolized patent ductus arteriosus device causing
      erosion of the aortic wall.
AB  - We report a case of 2-year-old boy who presented late after PDA device
      embolization to descending aorta. He had mild obstruction with erosion of the
      intimal layer of descending aorta caused by the device that was successfully
      retrieved surgically with reconstruction of the aortic segment.

PMID- 22407457
TI  - Development of a rapid and practical mutation screening assay for human lung
      adenocarcinoma.
AB  - Mortality after initial diagnosis of lung cancer is higher than from any other
      cancer. Although mutations in several genes, such as EGFR and K-ras, have been
      associated with clinical outcome, technical complexity, cost and time have
      rendered routine screening prohibitive for most lung cancer patients prior to
      treatment. In this study, using both novel and established technologies, we
      developed a clinically practical assay to survey the status of three frequently
      mutated genes in lung cancer (EGFR, K-ras and TP53) and two genes (BRAF and beta
      catenin) with known hotspot mutations in many other cancers. A single 96-well
      plate was designed targeting a total of 14 fragments (16 exons) from EGFR, K-ras,
      TP53, BRAF and beta-catenin. In 96 lung adenocarcinoma patients, the mutation
      frequencies of three major genes (EGFR, K-ras and TP53) were between 21-24%.
      Fifty-six out of 96 (58%) patients had a mutation in at least one of the five
      genes. K-ras mutations positively correlated with smoking pack-years (p=0.035).
      EGFR mutations were frequent in never-smokers (p=0.0007), Asians (p=0.0204) and
      non-stage I lung cancer (p=0.016). There was also a trend towards an association
      between the presence of any mutation and improved recurrence-free survival
      (p=0.070). We demonstrate that our novel multigene mutation assay technology can
      rapidly and cost-effectively screen for mutations in lung adenocarcinoma. This
      screening assay can be used in the clinical setting for the large-scale
      validation of prognosis and/or predicting therapeutic response so that the
      majority of lung cancer patients can benefit from leveraging up-to-date knowledge
      on how mutation profiles may influence treatment options.

PMID- 22407458
TI  - Invited commentary: applying psychodynamic developmental assessment to explore
      mental functioning in adolescents.
AB  - Recent publications in the Journal of Youth and Adolescence present a variety of
      topics exploring adolescents' mental functioning in the twenty first century.
      Conceptually, many of the articles address the intriguing, though rarely
      explicit, question of developmental continuities and change from adolescence to
      adulthood. Such investigations, which are particularly prominent in articles that
      discuss personality dispositions such as impulsivity or lack of empathy and their
      relationship to emotionally disturbed or maladaptive interpersonal behaviors,
      examine interactional effects of these dispositions within the personality
      context matrix. From a methodological perspective, however, the major tools used
      for assessing personality dispositions are self-report inventories while
      performance-based methods, previously defined as projective tests, are not used
      at all despite the wide range of empirical studies that provide support for their
      psychometric properties. This commentary suggests that applying a theoretically
      based, multi-method assessment procedure in empirical research would be most
      fruitful for any study aimed at exploring mental functioning in adolescents. As
      an example, I would use the Rorschach Inkblot Method, currently being
      internationally considered as the most frequently applied personality test for
      assessing adolescents. Implications for research, practice and policy decision
      making are discussed.

PMID- 22407459
TI  - Expression of angiotensinogen and receptors for angiotensin and prorenin in the
      monkey and human substantia nigra: an intracellular renin-angiotensin system in
      the nigra.
AB  - We have previously obtained in rodents a considerable amount of data suggesting a
      major role for the brain renin-angiotensin system (RAS) in dopaminergic neuron
      degeneration and potentially in Parkinson's disease. However, the presence of a
      local RAS has not been demonstrated in the monkey or the human substantia nigra
      compacta (SNc). The present study demonstrates the presence of major RAS
      components in dopaminergic neurons, astrocytes and microglia in both the monkey
      and the human SNc. Angiotensin type 1 and 2 and renin-prorenin receptors were
      located at the surface of dopaminergic neurons and glial cells, as expected for a
      tissular RAS. However, angiotensinogen and receptors for angiotensin and renin
      prorenin were also observed at the cytoplasm and nuclear level, which suggests
      the presence of an intracrine or intracellular RAS in monkey and human SNc.
      Although astrocytes and microglia were labeled for angiotensin and prorenin
      receptors in the normal SNc, most glial cells appeared less immunoreactive than
      the dopaminergic neurons. However, our previous studies in rodent models of PD
      and studies in other animal models of brain diseases suggest that the RAS
      activity is significantly upregulated in glial cells in pathological conditions.
      The present results together with our previous findings in rodents suggest a
      major role for the nigral RAS in the normal functioning of the dopaminergic
      neurons, and in the progression of the dopaminergic degeneration.

PMID- 22407460
TI  - Procollagen propeptides: serum markers for atrial fibrosis?
AB  - BACKGROUND: Atrial fibrosis and its spatial heterogeneity are regarded as a
      substrate for the perpetuation of atrial arrhythmias. During collagen synthesis
      and degradation, collagen propeptides and telopeptides are released into the
      blood. This study tested the hypothesis that serum markers of collagen turnover
      correlate with atrial fibrosis. METHODS: We prospectively included 28 patients in
      sinus rhythm undergoing cardiac surgery. Plasma concentrations of the carboxy-
      and amino-terminal propeptide of procollagen type-I (PICP and PINP) and type-III
      (PIIINP), and the C-terminal telopeptide of type-I collagen (ICTP) were
      determined. Interstitial fibrosis of left (n = 10) and right atrial appendages (n
      = 28) was analyzed histologically. RESULTS: We found a correlation between left
      and right atrial fibrosis (r (s) = 0.79, p < 0.01). Interestingly, the higher the
      interstitial collagen content, the higher was the spatial heterogeneity of
      fibrosis (r (s) = 0.90, p < 0.001). However, PICP, PIIINP, and ICTP were not
      correlated to left or right atrial collagen content, or to the spatial
      heterogeneity of atrial fibrosis. There was a weak and even negative correlation
      between the serum PINP concentration and the degree of fibrosis in both the left
      and the right atrium (r (s) = -0.65 (p = 0.04) and r (s) = -0.42 (p = 0.03),
      respectively). CONCLUSIONS: A high degree of interstitial atrial fibrosis
      indicates a high degree of spatial heterogeneity of interstitial collagen.
      Although serum PICP is known to be correlated with ventricular fibrosis, this and
      other serum markers of collagen turnover (PINP, PIIINP, and ICTP) do not directly
      reflect atrial fibrosis in patients with severe cardiac disease.

PMID- 22407461
TI  - Troponin T levels in patients with acute heart failure: clinical and prognostic
      significance of their detection and release during hospitalisation.
AB  - AIMS: Myocardial injury during an episode of acute heart failure (AHF) may be
      important for patents' outcome. We hypothesised that an increase of cardiac
      troponin levels (cTnT) during hospitalisation, in patients with undetectable
      levels on admission (cTnT release), may be a more specific marker of myocardial
      damage. With this aim, we assessed the clinical and prognostic significance of
      high serum cTnT levels at the time of admission and that of cTnT release in 198
      consecutive patients admitted for AHF and with no signs of acute coronary
      syndrome. METHODS AND RESULTS: cTnT levels were serially measured at the time of
      admission, and after 6 and 12 h, in 198 consecutive patients admitted for AHF and
      with no signs of acute coronary syndrome. cTnT was detectable (>0.01 ng/mL) in
      102 patients (52 %) and positive for myocardial necrosis (>0.03 ng/mL) in 78
      patients (39 %). Negative cTnT at the time of admission became positive at 6
      and/or 12 h in 36 (18 %) patients. Patients with increased cTnT levels were more
      likely to have coronary artery disease, hypertension, diabetes, and renal
      dysfunction. During a median follow-up duration of 247 days (IQR 96-480 days),
      the detection of increased cTnT levels was associated with a higher rate of all
      cause deaths and, for cTnT release, all-cause death and cardiovascular
      rehospitalisation rate. CTnT release was an independent predictor of all-cause
      death and cardiovascular rehospitalisation, along with glomerular filtration
      rate, and the administration of inotropic agents during the initial
      hospitalisation. CONCLUSIONS: Increased cTnT levels are a frequent finding in
      patients with AHF. They are more likely to occur in patients with comorbidities
      and are associated with poorer outcomes. cTnT release is an independent predictor
      of poorer outcomes.

PMID- 22407463
TI  - [Antibiotic therapy of acute uncomplicated diverticulitis :  Results of a
      prospective randomized multicenter study].

PMID- 22407462
TI  - Increased coronary vasoconstrictor response to acetylcholine in women with chest
      pain and normal coronary arteriograms (cardiac syndrome X).
AB  - AIMS: Cardiac syndrome X (CSX) is characterized by exercise-induced angina,
      positive exercise stress-test responses and angiographically normal coronary
      arteries. The condition characteristically affects more women than men and is
      often associated with coronary microvascular dysfunction, i.e., abnormal
      vasodilatory responses. Recent clinical observations suggest that increased
      coronary vasoconstriction may have a pathogenic role in CSX. We therefore sought
      to assess the prevalence of increased epicardial and microvascular coronary
      vasoconstriction in women with CSX. METHODS AND RESULTS: Among 1,120 consecutive
      women with angina undergoing diagnostic coronary angiography 39 fulfilled
      criteria for CSX (mean age 63 +/- 9 years) and were included in the study (27
      also complained about rest angina). Five women without angina (mean age 64 +/- 24
      years) and normal coronary arteriograms served as controls. Patients and controls
      underwent intracoronary acetylcholine testing with a standardized protocol.
      Severe (>=75 % diameter reduction) epicardial constriction developed in 12 CSX
      patients (31 %) with reproduction of their angina in 10. All 12 patients showed
      diffuse epicardial constriction affecting mainly the distal coronary segments.
      Twenty-two CSX patients (56 %) experienced their usual angina without epicardial
      constriction of which 21 had ischemic ECG shifts. The remaining five CSX patients
      (13 %) had no angina or constriction in response to acetylcholine. None of the
      control patients had angina or constriction during ACH testing. CONCLUSION:
      Increased epicardial as well as microvascular coronary constriction in response
      to acetylcholine are frequent findings in women with CSX. The results indicate
      that inappropriate coronary constriction is likely to contribute to the anginal
      symptoms of these patients. The ACH-test may be useful in the clinical setting to
      unmask this vasomotor disorder.

PMID- 22407464
TI  - Synthesis and evaluation of novel aza-caged Garcinia xanthones.
AB  - Inspired by the therapeutic potential of the simplified caged xanthones, we have
      developed a chemical strategy for synthesizing novel aza-caged Garcinia analogues
      through a regioselective Claisen/Diels-Alder cascade reaction. The origin of
      regioselectivity has been explained using the DFT method. We have further
      evaluated the cell proliferation and IKKbeta inhibitory activities of these
      compounds and studied their binding mode with IKKbeta by molecular docking. The
      results suggested that the aza-caged scaffold provides a suitable modification
      site and the introduction of a hydrophobic moiety leads to improvement in the
      cytotoxicity and IKKbeta inhibitory activity. The aza-caged compound 6c exhibited
      an IC(50) value of 2.68, 2.10, 8.02 MUM against the HepG2, A549 cells and
      IKKbeta, respectively. Mechanism studies with 6c showed that the aza-caged
      compounds induce apoptosis and cell cycle S phase arrest in A549 cells.

PMID- 22407465
TI  - A proposal for quality standards for measuring medication adherence in research.
AB  - A decade after widespread recognition that adherence to medication regimens is
      key to antiretroviral effectiveness, considerable controversy remains regarding a
      "gold standard" for adherence measurement. Each adherence measurement approach
      has strengths and weaknesses and each rests on specific assumptions. The range of
      assumptions regarding adherence measurement and the diversity with which each
      approach is implemented strongly suggest that the evaluation of a particular
      measure outside of the context in which it was used (e.g. the study's operational
      protocol) may result in undeserved confidence or lack of confidence in study
      results. The purpose of this paper is to propose a set of best practices across
      commonly used measurement methods. Recommendations regarding what information
      should be included in published reports regarding how adherence was measured are
      provided to promote improvement in the quality of measurement of medication
      adherence in research.

PMID- 22407466
TI  - Iron levels change in larval Heliothis virescens tissues following baculovirus
      infection.
AB  - Inductively coupled plasma mass spectrometry and (59)Fe radiotracers were used to
      investigate changes in levels of Fe in the tissues of 4th instar Heliothis
      virescens larvae following infection with Helicoverpa zea single
      nucleopolyhedrovirus (HzSNPV) or with Autographa californica multiple
      nucleopolyhedrovirus. Baculovirus infection led to significant changes in
      hemolymph Fe levels late in infection. (24)Na radiotracer ingested by 4th instar
      larvae was rapidly cleared to nearly undetectable levels 6 h post-ingestion. In
      contrast, (59)Fe radiotracer fed to 4th instar larvae declined within the first
      few hours of ingestion and then remained constant at approximately 60% of the
      initial tracer activity. While Fe radiotracer levels among larval tissues
      changed, whole insect tracer levels did not decline from 6 to 60 h post
      ingestion. Tissues from HzSNPV larvae had higher radiotracer levels in the
      hemolymph and midgut 36 and 60 h post-infection. The protein-bound/free ratio of
      (59)Fe was significantly higher in baculovirus infected hemolymph than in
      uninfected hemolymph at 60 h post-infection, indicating that Fe released from
      damaged cells is protein-bound. In both studies, hemolymph Fe levels were higher
      in HzSNPV infected larvae. This first study of tissue Fe levels during viral
      infection of an insect clearly demonstrates that Fe homeostasis is substantially
      disrupted.

PMID- 22407467
TI  - Effect of different levels of copper and molybdenum supplements on serum lipid
      profiles and antioxidant status in cashmere goats.
AB  - An experiment was conducted to investigate on the effects of different levels of
      copper (Cu: 0, 19, and 38 mg/kg) and molybdenum (Mo: 0 and 5 mg/kg) supplements
      and the interaction of these two factors on serum lipid profiles and antioxidant
      status in cashmere goats during the cashmere fiber growing period. Thirty-six
      Liaoning cashmere goats (approximately 1.5 years of age; 27.53+/-1.38 kg of body
      weight) were assigned to one of six treatments in a completely randomized design
      involving a 2*3 factorial arrangement. Goats were housed in individual pens and
      fed with Chinese wild rye- and alfalfa hay-based diet containing 4.72 mg Cu/kg,
      0.16 mg Mo/kg, and 0.21 % S for 84 days. Blood samples were collected on day 84.
      The triglyceride concentration did not differ among treatments (P>0.05).
      Supplemental Cu, regardless of Mo level, decreased (P<0.05) the concentrations of
      serum total cholesterol and low density lipoprotein cholesterol, and increased
      (P<0.05) the concentration of serum high density lipoprotein cholesterol, but
      there were no differences (P>0.05) in these values between Cu-supplemented
      groups. Supplemental Cu increased (P<0.05) the activities of serum ceruloplasmin
      (Cp), Cu-zinc superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px),
      and decreased (P<0.05) the malondialdehyde content. The serum GSH-Px activity was
      also increased (P<0.05) by Mo supplementation. There was a tendency of the
      interaction effects of Cu and Mo on the activities of Cp (P=0.094), SOD
      (P=0.057), and GSH-Px (P=0.062), and goats fed with 19 mg Cu/kg in the absence of
      Mo tended to show the highest serum SOD activity, while goats fed with 38 mg
      Cu/kg with 5 mg Mo/kg tended to show the highest values of serum Cp and GSH-Px.
      Addition of Cu, Mo, or their interaction had no influence (P>0.05) on the
      activities of serum glutamate oxaloacetate transaminase, glutamate pyruvate
      transaminase, and lactate dehydrogenase, and the concentrations of serum glucose
      and total protein. In conclusion, addition of 19 mg Cu/kg in the absence of Mo
      (the total dietary Cu level of 23.72 mg/kg) was recommended for altering the fat
      metabolism and obtaining the optimal antioxidant activity of cashmere goats,
      while 38 mg Cu/kg should be supplemented when 5 mg Mo/kg was added in the basal
      diet (the total dietary level of 42.72 mg Cu/kg, 5.16 mg Mo/kg, and 0.21 % S)
      during the cashmere growing period.

PMID- 22407468
TI  - In utero and lactational lanthanum exposure induces olfactory dysfunction
      associated with downregulation of betaIII-tubulin and olfactory marker protein in
      young rats.
AB  - We evaluated the role of betaIII-tubulin in the morphology of olfactory receptor
      neuron (ORN) and olfactory dysfunction in offspring caused by prenatal and
      postnatal lanthanum exposure. Pregnant rats were exposed to 0.25% lanthanum
      chloride in drinking water from gestational day (GD) 7 until postnatal day 21.
      From postnatal day 23 until postnatal day 28, pups were examined with buried food
      pellet and olfactory maze test. The ultrastructural features of ORNs in the
      olfactory epithelium (OE) were observed by transmission electron microscope. The
      expression of betaIII-tubulin and olfactory marker protein (OMP) in the tissue
      sections and homogenates of OE were, respectively, measured by immunodetection
      and western blot. Behavioral analysis of olfaction showed that lanthanum chloride
      exposure induced olfactory dysfunction. Offsprings exposed to lanthanum chloride
      showed enlarged ORN knobs and a decreased number of cilia. In addition, the
      levels of OMP and betaIII-tubulin expression in lanthanum chloride exposure
      offsprings significantly decreased. Developmental lanthanum exposure could impair
      olfaction, and this deficit may be attributed to the downregulation of betaIII
      tubulin and OMP in the OE.

PMID- 22407469
TI  - Autophagic activity in the mouse urinary bladder urothelium as a response to
      starvation.
AB  - The urinary bladder urothelium is subjected to mechanical forces during cycles of
      distension and contraction, and its superficial cells are constantly flushed by
      toxic urine. Yet, the urothelium shows a very slow turnover of cells and
      superficial cells are extremely long lived. Autophagy has a well-known role in
      tissue homeostasis and serves as a protective mechanism against cellular stress.
      Therefore, the presence of autophagy as one of possible processes of survival in
      an unpleasant environment and during long lifetime of superficial cells was
      examined in mouse urothelium. We detected and evaluated autophagic activity of
      superficial urothelial cells under normal and stress conditions, caused by short
      term starvation of newborn and 24-h-starved adult mice. Immunolabeling and
      Western blotting of essential effectors of autophagy, LC3 and Beclin 1, showed a
      weak signal in superficial urothelial cells. On the other hand, ultrastructural
      analysis, which proved to be the most reliable method in our study, revealed the
      presence of autophagic vacuoles, some of them containing specific urothelial
      structures, fusiform vesicles. Quantitative analysis showed increased autophagy
      in newborn and starved mice in comparison to a low basic level of autophagy in
      the urothelium of normal mice. Interestingly, some superficial cells of adults
      and neonates exhibit intense immunoreactions against LC3 and Beclin 1 and the
      typical ultrastructural characteristics of autophagy-dependent cell death. We
      conclude that autophagy, despite low basic activity under physiological
      conditions, plays an important role in urothelial homeostasis and stability under
      stress.

PMID- 22407470
TI  - Children and adolescents with fetal alcohol syndrome (FAS): better social and
      emotional integration after early diagnosis.
AB  - BACKGROUND: Alcoholism during pregnancy is one of the most common factors in
      western societies causing persisting congenital and multiple physical as well as
      neurological impairments. Finding the diagnosis at first sight puts medical
      professionals into a demanding situation. Therefore the objective of this study
      was to detect patients' developmental characteristics with the main focus on the
      necessity of the diagnosis itself. PATIENTS: 125 young patients, whose diagnosis
      of fetal alcohol syndrome (FAS) was made at the Muenster University Hospital,
      were followed up. METHODS: Biographic details such as living conditions, health,
      developmental problems and educational career were gathered using a structured
      interview. The diagnosis itself and the impact of this on the patients were also
      explored. RESULTS: Patients displayed characteristics of a less mature trait of
      character. The majority were looked after by foster parents. High rates of social
      and developmental problems could be found. The diagnosis was identified as a
      protective factor, with significantly better outcomes for patients being
      diagnosed in early childhood. A diagnosis established later in life was
      particularly helpful for the families and caregivers. Feelings of failure and
      self-blame could be diminished. CONCLUSIONS: The early detection of affected
      children has to be improved as receiving the correct diagnosis, despite the
      persistent impairments, is of major benefit for both patients and their families.

PMID- 22407471
TI  - [Guideline for antiretroviral therapy of HIV-infected children and adolescents].
AB  - The HIV-infection in adults or children and adolescent differs substantially.
      Differences include the mode of infection, viral dynamics facing a developing
      immune system and the clinical course of the infection. In addition to the
      virological, immunological and epidemiological aspects the psychosocial situation
      is also very different. The above aspects and the decreased number of
      antiretroviral substances underline the need for specific guidelines for HIV
      therapy in children and adolescents. The German Pediatric Working group AIDS
      (PAAD) has formulated this guideline in 2011 based on new study results, changes
      in international recommendations and newly available drugs.

PMID- 22407472
TI  - Left ventricular function impairment in patients with normal-weight obesity:
      contribution of abdominal fat deposition, profibrotic state, reduced insulin
      sensitivity, and proinflammatory activation.
AB  - BACKGROUND: Obesity predisposes to left ventricular (LV) dysfunction and heart
      failure; however, the risk of these complications has not been assessed in
      patients with a normal body mass index (BMI) but increased body fat content
      (normal-weight obesity, NWO). We hypothesized that LV performance in NWO may be
      impaired and sought to investigate potential contributors to cardiac functional
      abnormalities. METHODS AND RESULTS: One hundred sixty-eight subjects (age, 38+/-7
      years) with BMI <25kg/m(2) and no history of any disease affecting the myocardium
      were classified on the basis of body fat content into 2 groups: with NWO and
      without NWO. Echocardiographic indices of LV systolic and diastolic function,
      including myocardial velocities and deformation, serological fibrosis markers,
      indicators of proinflammatory activation, and metabolic control, were evaluated.
      Subjects with NWO demonstrated impaired LV systolic and diastolic function,
      increased fibrosis intensity (assessed by procollagen type I carboxy-terminal
      propeptide [PICP]), impaired insulin sensitivity, and increased proinflammatory
      activation as compared with individuals with normal body fat. The independent
      correlates of LV systolic and diastolic function variables were as follows: for
      strain, IL-18 (beta=-0.17, P<0.006), C-reactive protein (beta=-0.20, P<0.002) and
      abdominal fat deposit (beta=-0.20, P<0.003); for tissue S velocity, PICP (beta=
      0.21, P<0.002) and abdominal fat deposit (beta=-0.43, P<0.0001); for tissue E
      velocity, abdominal fat deposit (beta=-0.30, P<0.0001), PICP (beta=-0.31,
      P<0.0001) and homeostasis model assessment of insulin resistance index (HOMA IR;
      beta=-0.20, P<0.002); and for E/e'-PICP, IL-18 (both beta=0.18, P<0.01) and HOMA
      IR (beta=0.16, P<0.04). CONCLUSIONS: In patients with NWO, subclinical
      disturbances of LV function are independently associated with the extent of
      abdominal fat deposit, profibrotic state (as reflected by circulating PICP),
      reduced insulin sensitivity, and proinflammatory activation.

PMID- 22407473
TI  - Large magnetoresistance in few layer graphene stacks with current perpendicular
      to plane geometry.
AB  - A large magnetoresistance (MR) effect of few-layers graphene between two non
      magnetic metal electrodes with current perpendicular to graphene plane is
      studied. A non-saturation and anisotropic MR with the value over 60% at 14 T is
      observed in a two-layer graphene stack at room temperature. The resistance of the
      device is only tens of ohms, having the advantage of low power consumption for
      magnetic device applications.

PMID- 22407474
TI  - Society position statement : Canadian Cardiovascular Society/Canadian
      Anesthesiologists' Society/Canadian Heart Rhythm Society joint position statement
      on the perioperative management of patients with implanted pacemakers,
      defibrillators, and neurostimulating devices.
AB  - PURPOSE: There are more than 200,000 Canadians living with permanent pacemakers
      or implantable defibrillators, many of whom will require surgery or invasive
      procedures each year. They face potential hazards when undergoing surgery;
      however, with appropriate planning and education of operating room personnel,
      adverse device-related outcomes should be rare. This joint position statement
      from the Canadian Cardiovascular Society (CCS) and the Canadian
      Anesthesiologists' Society (CAS) has been developed as an accessible reference
      for physicians and surgeons, providing an overview of the key issues for the
      preoperative, intraoperative, and postoperative care of these patients. PRINCIPAL
      FINDINGS: The document summarizes the limited published literature in this field,
      but for most issues, relies heavily on the experience of the cardiologists and
      anesthesiologists who contributed to this work. This position statement outlines
      how to obtain information about an individual's type of pacemaker or implantable
      defibrillator and its programming. It also stresses the importance of determining
      if a patient is highly pacemaker-dependent and proposes a simple approach for
      nonelective evaluation of dependency. Although the document provides a
      comprehensive list of the intraoperative issues facing these patients, there is a
      focus on electromagnetic interference resulting from electrocautery and practical
      guidance is given regarding the characteristics of surgery, electrocautery,
      pacemakers, and defibrillators which are most likely to lead to interference.
      CONCLUSIONS: The document stresses the importance of preoperative consultation
      and planning to minimize complications. It reviews the relative merits of
      intraoperative magnet use vs reprogramming of devices and gives examples of
      situations where one or the other approach is preferable.

PMID- 22407475
TI  - Microcirculatory alterations after cardiopulmonary bypass as assessed with near
      infrared spectroscopy: a pilot study.

PMID- 22407476
TI  - Classification of multichannel EEG patterns using parallel hidden Markov models.
AB  - In this paper, a parallel hidden-Markov-model (PHMM)-based approach is proposed
      for the problem of multichannel electroencephalogram (EEG) patterns
      classification. The approach is based on multi-channel representation of the EEG
      signals using a parallel combination of HMMs, where each model represents a
      particular channel. The performance of the proposed algorithm is studied using an
      artificial EEG database, and two real EEG databases: a database of two classes of
      EEGs elicited during a task of imagery of hand upward and downward movements of a
      computer screen cursor (db Ia), and a database of two classes of sensorimotor
      EEGs elicited during a feedback-regulated left-right motor imagery task (db III).
      The results show that the proposed algorithm outperforms other commonly used
      methods with classification rate improvement of 2 and 10% for db Ia and db III,
      respectively. In addition, the proposed method outperforms a support vector
      machine classifier with a linear kernel, when both classifiers utilize the same
      feature set. The results also show that a model architecture which includes a
      left-to-right scheme with no skips, five states and three Gaussians, outperforms
      the other tested architectures due to the fact that it allows a better modeling
      of the temporal sequencing of the EEG components.

PMID- 22407477
TI  - All night analysis of time interval between snores in subjects with sleep apnea
      hypopnea syndrome.
AB  - Sleep apnea-hypopnea syndrome (SAHS) is a serious sleep disorder, and snoring is
      one of its earliest and most consistent symptoms. We propose a new methodology
      for identifying two distinct types of snores: the so-called non-regular and
      regular snores. Respiratory sound signals from 34 subjects with different ranges
      of Apnea-Hypopnea Index (AHI = 3.7-109.9 h(-1)) were acquired. A total number of
      74,439 snores were examined. The time interval between regular snores in short
      segments of the all night recordings was analyzed. Severe SAHS subjects show a
      shorter time interval between regular snores (p = 0.0036, AHI cp: 30 h(-1)) and
      less dispersion on the time interval features during all sleep. Conversely, lower
      intra-segment variability (p = 0.006, AHI cp: 30 h(-1)) is seen for less severe
      SAHS subjects. Features derived from the analysis of time interval between
      regular snores achieved classification accuracies of 88.2 % (with 90 %
      sensitivity, 75 % specificity) and 94.1 % (with 94.4 % sensitivity, 93.8 %
      specificity) for AHI cut-points of severity of 5 and 30 h(-1), respectively. The
      features proved to be reliable predictors of the subjects' SAHS severity. Our
      proposed method, the analysis of time interval between snores, provides promising
      results and puts forward a valuable aid for the early screening of subjects
      suspected of having SAHS.

PMID- 22407478
TI  - Optimization and validation of organochlorine compounds in adipose tissue by SPE
      gas chromatography.
AB  - Scientific evidence has shown an association between organochlorine compounds
      (OCC) exposure and human health hazards. Concerning this, OCC detection in human
      adipose samples has to be considered a public health priority. This study
      evaluated the efficacy of various solid-phase extraction (SPE) and cleanup
      methods for OCC determination in human adipose tissue. Octadecylsilyl endcapped
      (C18-E), benzenesulfonic acid modified silica cation exchanger (SA), poly(styrene
      divinylbenzene (EN) and EN/RP18 SPE sorbents were evaluated. The relative sample
      cleanup provided by these SPE columns was evaluated using gas chromatography with
      electron capture detection (GC-ECD). The C18-E columns with strong homogenization
      were found to provide the most effective cleanup, removing the greatest amount of
      interfering substance, and simultaneously ensuring good analyte recoveries higher
      than 70%. Recoveries > 70% with standard deviations (SD) < 15% were obtained for
      all compounds under the selected conditions. Method detection limits were in the
      0.003-0.009 mg/kg range. The positive samples were confirmed by gas
      chromatography coupled with tandem mass spectrometry (GC-MS/MS). The highest
      percentage found of the OCC in real samples corresponded to HCB, o,p'-DDT and
      methoxychlor, which were detected in 80 and 95% of samples analyzed respectively.

PMID- 22407479
TI  - miR-764-5p promotes osteoblast differentiation through inhibition of CHIP/STUB1
      expression.
AB  - Differentiation of committed precursor cells into the osteoblast lineage is
      tightly regulated by several factors, including Runx2 and BMP2. We previously
      reported that C terminus of Hsc70-interacting protein/STIP1 homology and U-Box
      containing protein 1 (CHIP/STUB1) negatively regulated osteoblast differentiation
      through promoting Runx2 protein degradation. However, how CHIP is regulated
      during osteoblast differentiation remains unknown. In this study, we found that
      miR-764-5p is up-expressed during the osteoblast differentiation in calvarial and
      osteoblast progenitor cells, coupled with down-expression of CHIP protein. We
      observed that forced expression or inhibition of miR-764-5p decreased or
      increased the CHIP protein level through affecting its translation by targeting
      the 3'-UTR region. Perturbation of miR-764-5p resulted in altered differentiation
      fate of osteoblast progenitor cells and the role of miR-764-5p was reversed by
      overexpression of CHIP, whereas depletion of CHIP impaired the effect of miR-764
      5p. Our data showed that miR-764-5p positively regulates osteoblast
      differentiation from osteoblast progenitor cells by repressing the translation of
      CHIP protein.

PMID- 22407480
TI  - An industrial perspective on contemporary applications of PBPK models in drug
      discovery and development.

PMID- 22407481
TI  - Night eating in obese treatment-seeking Hispanic patients with and without binge
      eating disorder.
AB  - OBJECTIVE: To examine the frequency of night eating (NE) and its relation to
      binge eating disorder (BED), eating-disorder psychopathology, depression, and
      metabolic variables in treatment-seeking obese Hispanic men and women. METHOD: A
      consecutive series of 79 obese monolingual Spanish-speaking-only Hispanic
      patients with BED (N = 40) and without BED (N = 39) were reliably assessed by
      bilingual research-clinicians using Spanish-language versions of semistructured
      interviews and measures. RESULTS: Overall, 38% (N = 30) of the 79 patients
      reported regular NE (>=4 days/month). NE and BED were significantly associated;
      70% (21/30) of NE versus 18% (9/49) of non-NE had BED. Patients with NE reported
      greater frequency of binge-eating and higher levels of eating-disorder
      psychopathology and depression than non-NE patients; group differences in eating
      disorder psychopathology and depression levels persisted after controlling for
      BED status. The NE and non-NE groups did not differ significantly in BMI or
      metabolic variables. DISCUSSION: In obese treatment-seeking Hispanic patients, NE
      and BED were significantly associated and NE was associated with heightened
      eating-disorder psychopathology and depression even after controlling for BED
      status.

PMID- 22407482
TI  - Identity processes and coping strategies in college students: short-term
      longitudinal dynamics and the role of personality.
AB  - Coping strategies and identity processes are hypothesized to influence one
      another over time. This three-wave longitudinal study (N = 458; 84.9% women)
      examined, for the first time, how and to what extent identity processes (i.e.,
      commitment making, identification with commitment, exploration in breadth,
      exploration in depth, and ruminative exploration) and coping strategies (i.e.,
      problem solving, social support seeking, and avoidance) predicted one another
      over time. Cross-lagged analyses indicated that processes of identity exploration
      seemed especially to be intertwined with different coping strategies over time,
      suggesting that identity exploration may resemble problem-solving behavior on the
      pathway to an achieved identity. Commitment processes were found to be influenced
      by certain coping strategies, although identification with commitment also
      negatively influenced avoidance coping. These temporal sequences remained
      significant when controlling for baseline levels of Big Five personality traits.
      Hence, evidence was obtained for reciprocal pathways indicating that coping
      strategies and identity processes reinforce one another over time in college
      students.

PMID- 22407483
TI  - Synthesis of aromatic compounds by catalytic C-C bond activation of biphenylene
      or angular [3]phenylene.
AB  - Substituted phenanthrenes and picenes were easily prepared by reaction of
      biphenylene or angular [3]phenylene with various alkynes in the presence of a
      catalytic amount of [IrCl(cod)](2) /dppe (cod=1,5-cyclooctadiene, dppe=1,2
      bis(diphenylphosphino)ethane). The reaction is based on C-C bond activation of
      the cyclobutane ring. The reaction tolerates the presence of bulky groups on the
      alkyne, such as the ferrocene moiety. In addition, a catalytic system based on
      [RhCl(cod)](2)/dppe enabled the, hitherto unreported, reaction of biphenylene
      with nitriles to provide phenanthridines.

PMID- 22407484
TI  - gamma-Glutamylamines and neurodegenerative diseases.
AB  - Transglutaminases catalyze the formation of gamma-glutamylamines utilizing
      glutamyl residues and amine-bearing compounds such as lysyl residues and
      polyamines. These gamma-glutamylamines can be released from proteins by proteases
      in an intact form. The free gamma-glutamylamines can be catabolized to 5-oxo-L
      proline and the free amine by gamma-glutamylamine cyclotransferase. Free gamma
      glutamylamines, however, accumulate in the CSF and affected areas of Huntington
      Disease brain. This observation suggests transglutaminase-derived gamma
      glutamylamines may play a more significant role in neurodegeneration than
      previously thought. The following monograph reviews the metabolism of gamma
      glutamylamines and examines the possibility that these species contribute to
      neurodegeneration.

PMID- 22407485
TI  - Pharmacological characterization of the ghrelin receptor mediating its inhibitory
      action on inflammatory pain in rats.
AB  - Recent research suggests a role for ghrelin in the modulation of inflammatory
      disorders. However, the type of ghrelin receptor (GHS-R) involved in both the
      anti-inflammatory and anti-hyperalgesic actions of ghrelin remains to be
      characterized. In this study, we examined whether the inhibitory effect of
      ghrelin in the development of hyperalgesia and edema induced by intraplantar
      carrageenan administration depends on an interaction with GHS-R1a. Both central
      (1 nmol/rat, i.c.v.) and peripheral (40 nmol/kg, i.p.) administration of the
      selective GHS-R1a agonist EP1572 had no effect on carrageenan-induced
      hyperalgesia measured by Randall-Selitto test and paw edema. Furthermore, pre
      treatment with the selective GHS-R1a antagonist, D-lys(3)-GHRP-6 (3 nmol/rat,
      i.c.v.) failed to prevent the anti-hyperalgesic and anti-inflammatory effects
      exerted by central ghrelin administration (1 nmol/rat), thus indicating that the
      type 1a GHS-R is not involved in these peptide activities. Accordingly, both
      central (1 and 2 nmol/rat, i.c.v.) and peripheral (40 and 80 nmol/kg, i.p.)
      administration of desacyl-ghrelin (DAG), which did not bind GHS-R1a, induced a
      significant reduction of the hyperalgesic and edematous activities of
      carrageenan. In conclusion, we have shown for the first time that DAG shares with
      ghrelin an inhibitory role in the development of hyperalgesia, as well as the paw
      edema induced by carrageenan and that a ghrelin receptor different from type 1a
      is involved in the anti-inflammatory activities of the peptide.

PMID- 22407486
TI  - Down-regulated expression of apoptosis-associated genes APIP and UACA in non
      small cell lung carcinoma.
AB  - The Apaf-1 interacting protein (APIP) and the uveal autoantigen with coiled coil
      domains and ankyrin repeats (UACA) belong to endogenous regulators of the
      apoptosome apparatus, but their role in tumourigenesis and progression of non
      small cell lung carcinoma (NSCLC) is not known. Previous studies demonstrated
      that APIP inhibits the apoptosome-mediated procaspase-9 activation while UACA
      induces translocation of Apaf-1 from the cytoplasm into the nucleus. Here, we
      report for the first time that the expression of APIP and UACA genes is down
      regulated on the level of both mRNA and protein in NSCLC cells and tumours. In
      particular, the expression of APIP protein was strikingly decreased and the
      expression of UACA mRNA and protein was frequently down-regulated in NSCLC
      tumours of different histopathological types. Moreover, stage IA NSCLC tumours
      showed significantly lower expression of UACA mRNA compared to higher stage
      tumours. The weak increase of both APIP and UACA mRNA levels in the 5-aza-2'
      deoxycytidine-treated NSCLC cells indicates that mechanisms other than DNA
      methylation are involved in the regulation of APIP and UACA gene expression in
      these cancer cells. Taken together, the down-regulation of APIP and UACA
      expression suggests that the threshold to activate the apoptosome apparatus may
      be decreased in NSCLC cells due to the lack of APIP-mediated suppression and UACA
      assisted Apaf-1 nuclear entry. Moreover, the loss of UACA-assisted Apaf-1 nuclear
      translocation may underlie the failure of DNA damage checkpoint activation in
      NSCLC cells leading to their genomic instability.

PMID- 22407489
TI  - Reducing health inequalities: new data suggest that the English strategy was
      partially successful.

PMID- 22407488
TI  - Mass spectrometric comparison of N-glycan profiles from Caenorhabditis elegans
      mutant embryos.
AB  - The free-living nematode Caenorhabditis elegans is a well-characterized
      eukaryotic model organism. Recent glycomic analyses of the glycosylation
      potential of this worm revealed an extremely high structural variability of its N
      glycans. Moreover, the glycan patterns of each developmental stage appeared to be
      unique. In this study we have determined the N-glycan profiles of wild-type
      embryos in comparison to mutant embryos arresting embryogenesis early before
      differentiation and causing extensive transformations of cell identities, which
      allows to follow the diversification of N-glycans during development using mass
      spectrometry. As a striking feature, wild-type embryos obtained from liquid
      culture expressed a less heterogeneous oligosaccharide pattern than embryos
      recovered from agar plates. N-glycan profiles of mutant embryos displayed, in
      part, distinct differences in comparison to wild-type embryos suggesting
      alterations in oligosaccharide trimming and processing, which may be linked to
      specific cell fate alterations in the embryos.

PMID- 22407490
TI  - Application of high-speed countercurrent chromatography-evaporative light
      scattering detection for the separation of seven steroidal saponins from
      Dioscorea villosa.
AB  - INTRODUCTION: Steroidal saponins in Dioscorea species are chemically
      characterised as spirostanol and furostanol saponins, and have been used as
      standard marker compounds due to their chemotaxonomical significance and their
      important biological activities. OBJECTIVE: To design a simple, rapid and
      efficient method for the separation of steroidal saponins with a high degree of
      purity using high-speed countercurrent chromatography (HSCCC) coupled with
      evaporative light scattering detection (ELSD). METHODOLOGY: In the first step,
      reversed-phase mode HSCCC (flow rate: 1.5 mL/min; revolution speed: 800 rpm)
      using n-hexane:n-butanol:water [3:7:10 (v/v/v)] was employed to separate
      furostanol saponins from n-butanol soluble extracts of Dioscorea villosa. After
      the first HSCCC run, spirostanol saponins retained in the stationary phase were
      subjected to the second HSCCC (normal-phase mode; flow rate: 2.0 mL/min;
      revolution speed: 800 rpm). A two-phase solvent system composed of
      chloroform:methanol:isopropanol:water [10:6:1:4 (v/v/v/v)] was employed in the
      second HSCCC. The structures of isolates were elucidated by (1) H-NMR, (13)  C
      NMR, ESI-MS and HPLC analysis. RESULTS: Three furostanol saponins, parvifloside
      (27.3 mg), methyl protodeltonin (67.1 mg) and trigofoenoside A-1 (18.5 mg) were
      isolated from the n-butanol soluble extract of D. villosa by the first HSCCC run.
      Subsquent normal-phase HSCCC of the spirostanol-rich extract led to the
      separation of four spirostanol saponins: zingiberensis saponin I (15.2 mg),
      deltonin (31.5 mg), dioscin (7.7 mg) and prosapogenin A of dioscin (3.4 mg).

PMID- 22407491
TI  - Using graphene oxide high near-infrared absorbance for photothermal treatment of
      Alzheimer's disease.
AB  - A novel strategy to dissociate amyloid aggregation is presented, using localised
      heat generation from a clinically used amyloid staining dye, thioflavin-S (ThS)
      modified graphene oxide (GO) under NIR laser irradiation. Compared to traditional
      chemotherapies, photothermal therapy shows reduced side effects and improved
      selectivity and safety.

PMID- 22407492
TI  - Association of nonalcoholic fatty liver disease with low bone mass in
      postmenopausal women.
AB  - Osteoporosis is a disease associated with insulin resistant states such as
      central obesity, diabetes, and metabolic syndrome. Non-alcoholic fatty liver
      disease (NAFLD) is also increased in such conditions. However, little is known
      about whether osteoporosis and nonalcoholic fatty liver disease are etiologically
      related to each other or not. We examined whether bone mineral density (BMD) is
      associated with NAFLD in pre- and postmenopausal women. Four hundred eighty-one
      female subjects (216 premenopausal and 265 postmenopausal) were enrolled. Lumbar
      BMD was measured using dual-energy X-ray absorptiometry. Liver ultrasonography
      was done to check the severity of fatty liver. We excluded subjects with a
      secondary cause of liver disease. Blood pressure, lipid profile, fasting plasma
      glucose, alanine aminotransferase (ALT), aspartate aminotransferase, and body
      mass index were measured in every subject. Mean lumbar BMD was lower in subjects
      with NAFLD than those without NAFLD in postmenopausal women (0.98 +/- 0.01 vs.
      1.01 +/- 0.02 g/cm2, P = 0.046). Multiple correlation analysis revealed a
      significant association between mean lumbar BMD and NAFLD in postmenopausal
      subjects after adjusting for age, body mass index, ALT, smoking status, and
      alcohol consumption (beta coefficient -0.066, 95% CI -0.105 to -0.027, P =
      0.001). Even after adjusting the presence of metabolic syndrome, the significance
      was maintained (beta coefficient -0.043, 95% CI -0.082 to -0.004, P = 0.031).
      Lumbar BMD is related with NAFLD in postmenopausal females. We suggest that
      postmenopausal women with NAFLD may have a higher risk of osteoporosis than those
      without.

PMID- 22407493
TI  - Determining cut-off values for neck circumference as a measure of the metabolic
      syndrome amongst a South African cohort: the SABPA study.
AB  - The aim was to determine receiver operating characteristic (ROC) neck
      circumference (NC) cut offs best associated with the metabolic syndrome (MetS) in
      a South African cohort. We included 409 urban Africans and Caucasians and
      stratified them into gender and age groups (25-45 years; 45-65 years).
      Measurements included anthropometric, fasting overnight urine and biological
      markers for the MetS (systolic and diastolic blood pressure, glucose,
      triglycerides, and high density lipoprotein). ROC analysis determined
      pathological (NC) cut-points of 39 and 35 cm for young and older African men; 32
      and 35 cm for young and old African women; 40 and 41 cm for Caucasian men; 34 and
      33 cm for Caucasian women. Pathological NC cut-points significantly predicted
      MetS in all ethnic-gender-age groups except in African women (ORs 2.3-5.4; 95% CI
      1.36-16.5). Multiple regression analyses revealed that MetS prevalence and ROC
      cut-points were not associated with renal impairment in any groups. ROC NC cut
      points demonstrated that NC may be used as an additional anthropometric marker to
      predict the MetS in a South African cohort but not in African women.

PMID- 22407494
TI  - The effects of resistance training on ApoB/ApoA-I ratio, Lp(a) and inflammatory
      markers in patients with type 2 diabetes.
AB  - The purpose of this study was to investigate the effects of resistance training
      (RT) on novel cardiovascular risk factors in patients with type 2 diabetes
      mellitus (T2DM). We enrolled 52 overweight/obese, type 2 diabetic patients, with
      inadequate glycemic control (HbA1c > 6.5 %), but without overt diabetic vascular
      complications. Participants were randomly assigned into two equivalent groups (n
      = 26): (1) Resistance exercise group: subjects underwent a supervised RT program
      (3-times/week, 60 min/session, 2-3 sets of 8 machine-weight exercises, 60-80 % of
      one-repetition maximum). (2) Control group (CG): at study entrance, they received
      a structured exercise counseling to increase daily physical activity. Clinical
      parameters, cardiorespiratory capacity, glycemic and lipid profile,
      apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), Lipoprotein(a) [Lp(a)],
      insulin resistance (HOMA-IR), high-sensitivity CRP (hsCRP), fibrinogen were
      measured before and after 3 months. RT significantly reduced glycemic indexes,
      insulin resistance and systolic blood pressure, compared to CG (p < 0.05).
      Moreover, exercise-treated patients conferred a remarkable downregulation in ApoB
      levels (from 135.92 +/- 30.97 mg/dL to 85.9 +/- 26.46 mg/dL, p < 0.001) as
      compared to CG (from 126.33 +/- 36.59 mg/dL to 116.23 +/- 27.52 mg/dL, p = 0.872)
      (p < 0.001). Similarly, ApoB/ApoA-I ratio was considerably decreased in REG
      rather than CG (-0.32 +/- 0.09 vs 0.02 +/- 0.01, p < 0.001). Notably, ApoA-I,
      Lp(a), hsCRP, fibrinogen, the rest of lipid parameters, body weight and exercise
      capacity remained unaltered in both groups (p > 0.05). Among variables, HOMA-IR
      reduction was found to be an independent predictor of changes in ApoB/ApoA-I
      ratio (R (2) = 0.406, p = 0.041) in REG. Long-term RT ameliorated glycemic
      control, insulin sensitivity and ApoB/ApoA-I ratio in individuals with T2DM.
      Although we did not observe significant benefits in the rest of cardiovascular
      risk factors, our results indicate a merely beneficial impact of RT.

PMID- 22407497
TI  - Genomic profiling by whole-genome single nucleotide polymorphism arrays in Wilms
      tumor and association with relapse.
AB  - Despite the excellent survival rate of Wilms tumor (WT) patients, only
      approximately one-half of children who suffer tumor recurrence reach second
      durable remission. This underlines the need for novel markers to optimize initial
      treatment. We investigated 77 tumors using Illumina 370CNV-QUAD genotyping
      BeadChip arrays and compared their genomic profiles to detect copy number (CN)
      abnormalities and allelic ratio anomalies associated with the following
      clinicopathological variables: relapse (yes vs. no), age at diagnosis (<= 24
      months vs. >24 months), and disease stage (low stage, I and II, vs. high stage,
      III and IV). We found that CN gains at chromosome region 1q21.1-q31.3 were
      significantly associated with relapse. Additional genetic events, including
      allelic imbalances at chromosome arms 1p, 1q, 3p, 3q, and 14q were also found to
      occur at higher frequency in relapsing tumors. Interestingly, allelic imbalances
      at 1p and 14q also showed a borderline association with higher tumor stages. No
      genetic events were found to be associated with age at diagnosis. This is the
      first genome wide analysis with single nucleotide polymorphism (SNP) arrays
      specifically investigating the role of genetic anomalies in predicting WT relapse
      on cases prospectively enrolled in the same clinical trial. Our study, besides
      confirming the role of 1q gains, identified a number of additional candidate
      genetic markers, warranting further molecular investigations.

PMID- 22407498
TI  - Medical equipment classification: method and decision-making support based on
      paraconsistent annotated logic.
AB  - As technology evolves, the role of medical equipment in the healthcare system, as
      well as technology management, becomes more important. Although the existence of
      large databases containing management information is currently common, extracting
      useful information from them is still difficult. A useful tool for identification
      of frequently failing equipment, which increases maintenance cost and downtime,
      would be the classification according to the corrective maintenance data.
      Nevertheless, establishment of classes may create inconsistencies, since an item
      may be close to two classes by the same extent. Paraconsistent logic might help
      solve this problem, as it allows the existence of inconsistent (contradictory)
      information without trivialization. In this paper, a methodology for medical
      equipment classification based on the ABC analysis of corrective maintenance data
      is presented, and complemented with a paraconsistent annotated logic analysis,
      which may enable the decision maker to take into consideration alerts created by
      the identification of inconsistencies and indeterminacies in the classification.

PMID- 22407499
TI  - Metabolism studies of casticin in rats using HPLC-ESI-MS(n).
AB  - Casticin (3',5-dihydroxy-3, 4',6,7-tetramethoxyflavone) has been revealed to
      possess various kinds of pharmacological activities, including immunomodulatory,
      anti-hyperprolactinemia, anti-tumor and neuroprotetective activities. In order to
      gain an understanding of the biotransformation of casticin in vivo, a systematic
      method based on liquid chromatography-electrospray ionization tandem mass
      spectrometry (LC-ESI-MS(n) ) was developed to identify the metabolites of
      casticin in rats after oral administration of single dose of casticin at 200
      mg/kg. By comparing their changes in molecular masses (DeltaM), retention times
      and spectral patterns with those of the parent drug, the parent compound and 25
      metabolites were identified in rat plasma, urine and six selected tissues. This
      is the first systematic metabolism study of casticin in vivo. The results
      indicated that methylation, demethylation, glucuronidation and sulfation were the
      main biotransformation pathways of casticin in vivo.

PMID- 22407501
TI  - Microbotryozyma collariae gen. nov., sp. nov., a basidiomycetous yeast isolated
      from a plant bug Collaria oleosa (Miridae).
AB  - Two strains of a basidiomycetous yeast were derived from an insect trypanosomatid
      culture isolated from the intestine of a plant bug, Collaria oleosa (Heteroptera:
      Miridae), collected in Costa Rica. The yeast did not form ballistoconidia but
      reproduced only by budding. Teliospores were not observed in individual and
      crossed cultures of each strain. Morphological and other taxonomic
      characteristics of the yeast were similar to those of the species in the
      polyphyletic genus Rhodotorula. However, molecular phylogeny inferred from the
      internal transcribed spacers and D1/D2 region of the large subunit rRNA gene
      showed that the strains represent a new species placed among the smut fungi in
      the family Ustilentylomataceae, which includes Aurantiosporium subnitens,
      Fulvisporium restifaciens, Ustilentyloma fluitans, and Rhodotorula hordea. Given
      the well distinguished phylogenetic position of this novel species within the
      Ustilentylomataceae, we propose Microbotryozyma collariae gen. nov., sp. nov. to
      accommodate the yeast isolated from C. oleosa, with strain American Type Culture
      Collection MYA-4666(T) (= PRA303-1S = CBS 12537) designated as the type strain.

PMID- 22407500
TI  - The effect of adenosine A(2A) receptor antagonists on hydroxyl radical, dopamine,
      and glutamate in the striatum of rats with altered function of VMAT2.
AB  - It has been shown that a decreased vesicular monoamine transporter (VMAT2)
      function and the disruption of dopamine (DA) storage is an early contributor to
      oxidative damage of dopamine neurons in Parkinson's disease (PD). In our previous
      study, we demonstrated that adenosine A(2A) receptor antagonists suppressed
      oxidative stress in 6-hydroxydopamine-treated rats suggesting that this effect
      may account for neuroprotective properties of drugs. In the present study, rats
      were injected with reserpine (10 mg/kg sc) and 18 h later the effect of the
      adenosine A(2A) receptor antagonists 8-(3-chlorostyryl)caffeine (CSC) and 4-(2-[7
      amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM
      241385) on extracellular DA, glutamate and hydroxyl radical formation was studied
      in the rat striatum using in vivo microdialysis. By disrupting VMAT2 function,
      reserpine depleted DA stores, and increased glutamate and hydroxyl radical levels
      in the rat striatum. CSC (1 mg/kg) but not ZM 241385 (3 mg/kg) increased
      extracellular DA level and production of hydroxyl radical in reserpinised rats.
      Both antagonists decreased the reserpine-induced increase in extracellular
      glutamate. L-3,4-Dihydroxyphenylalanine (L-DOPA) (25 mg/kg) significantly
      enhanced extracellular DA, had no effect on reserpine-induced hydroxyl radical
      production and decreased extracellular glutamate concentration. CSC but not ZM
      241385 given jointly with L-DOPA increased the effect of L-DOPA on extracellular
      DA and augmented the reserpine-induced hydroxyl radical production. CSC and ZM
      241385 did not influence extracellular glutamate level, which was decreased by L
      DOPA. It seems that by decreasing the MAO-dependent DA metabolism rate, CSC
      raised cytosolic DA and by DA autoxidation, it induced hydroxyl radical
      overproduction. Thus, the methylxanthine A(2A) receptor antagonists bearing
      properties of MAO-B inhibitor, like CSC, may cause a risk of oxidative stress
      resulting from dysfunctional DA storage mechanism in early PD.

PMID- 22407502
TI  - The innate reactivity of a membrane associated peptide towards lipids: acyl
      transfer to melittin without enzyme catalysis.
AB  - The innate reactivity of the peptide melittin (H-GIGAVLKVLTTGLPALISWIKRKRQQ
      NH(2)) towards membrane lipids has been explored using LC-MS methods. The high
      sensitivity afforded by LC-MS analysis enabled acyl transfer to the peptide to be
      detected, within 4 h, from membranes composed of phosphocholines (PCs). Acyl
      transfer from PCs was also observed from mixtures of PC with phosphoserine (PS)
      or phosphoglycerol (PG). In the latter case, transfer from PG was also detected.
      The half-lives for melittin conversion varied between 24 h and 75 h, being
      fastest for POPC and slowest for DOPC/DMPG mixtures. The order of reactivity for
      amino groups on the peptide was N-terminus > K23 ? K21 > K7. Products arising
      from double-acylation of melittin were detected as minor components, together
      with a putative component derived from transesterification involving S18 of the
      peptide.

PMID- 22407503
TI  - Transforming growth factor-alpha induces endothelin receptor A expression in
      osteoarthritis.
AB  - Previously, our lab identified transforming growth factor-alpha (TGFalpha) as a
      novel factor involved in osteoarthritis (OA) in a surgical model of the disease.
      In the same study, we also observed increased transcript levels for endothelin
      receptor A (ET(A)R), a known contributor to cartilage pathology. To investigate
      the connection between TGFalpha and endothelin signaling in OA, primary articular
      chondrocytes and osteochondral explants were isolated from Sprague-Dawley rats
      and treated with vehicle or TGFalpha. Expression of ET(A)R protein and its
      encoding gene Ednra was assessed. Chondrocytes and cartilage explants were also
      treated with the endothelin receptor A/B antagonist Bosentan, in order to
      determine whether TGFalpha effects could be blocked. TGFalpha induced expression
      of ET(A)R protein and its encoding gene Ednra. In primary chondrocyte cultures,
      Bosentan did not block TGFalpha responses of the anabolic genes Sox9, Agc1, and
      Col2a1, but reduced the induction of Mmp13 and Ednra transcripts by TGFalpha. In
      osteochondral explants, the inhibitor partially blocked TGFalpha reduction of
      type II collagen, as well as induction of MMP-13 and type II collagen
      neoepitopes. TGFalpha induces ET(A)R expression in articular chondrocytes and
      receptor antagonism appears to block some TGFalpha-induced catabolic effects in a
      three-dimensional organ culture system. Thus, TGFalpha may be a therapeutic
      target upstream of ET(A)R in OA.

PMID- 22407504
TI  - Predicting human hepatic clearance from in vitro drug metabolism and transport
      data: a scientific and pharmaceutical perspective for assessing drug-drug
      interactions.
AB  - OBJECTIVES: Membrane transporters and metabolism are major determinants of the
      hepatobiliary elimination of drugs. This work investigates several key questions
      for drug development. Such questions include which drugs demonstrate transporter
      based clearance in the clinic, and which in vitro methods are most suitable for
      drug classification, i.e. transporter- vs metabolism-dependent compound class
      categories. Additional questions posed are: what is the expected quantitative
      change in exposure in the presence of a transporter- and/or metabolism-inhibiting
      drug, and which criteria should trigger follow-up clinical drug-drug interaction
      studies. METHODS: A well-established method for (human) liver clearance
      prediction that considers all four physiological processes driving hepatic drug
      elimination (namely sinusoidal uptake and efflux, metabolism and biliary
      secretion) was applied. Suspended hepatocytes, liver microsomes and sandwich
      cultured hepatocytes were used as in vitro models to determine the individual
      intrinsic clearance for 13 selected compounds with various physicochemical and
      pharmacokinetic properties. RESULTS: Using this in vitro-in vivo extrapolation
      method a good linear correlation was observed between predicted and reported
      human hepatic clearances. Linear regression analysis revealed much improved
      correlations compared with other prediction methods. CONCLUSIONS: The presented
      approach serves as a basis for accurate compound categorization within the
      Biopharmaceutics Drug Disposition Classification System (BDDCS) and was applied
      to anticipate metabolism- and transporter-based drug-drug interactions using
      different static prediction methods. A decision tree proposal is provided and
      helps to guide clinical studies on active processes influencing hepatic
      elimination. All recommendations in this paper are generally intended to support
      early pre-clinical and clinical drug development and the filing of a new drug
      application.

PMID- 22407505
TI  - Disk aromaticity of the planar and fluxional anionic boron clusters B20(-/2-).
AB  - The presence of excess electrons modifies the structural landscape and tends to
      extend the planarity of boron clusters. While the neutral B(20) is tubular, both
      the anion and dianion B(20)(-/2-) become planar. Geometrical features of the
      stable anions suggest the existence of a new type of cluster that is planar and
      doubly cyclic with one atom located at the center (see figure), as well as being
      fluxional.

PMID- 22407506
TI  - Interplay between H-bonding and alkyl-chain ordering in self-assembly of
      monodendritic L-alanine derivatives.
AB  - This paper reports on the synthesis and self-organizing properties of
      monodendrons consisting of L-alanine at the focal point and alkyl chains with
      different length at the periphery. The structures of thin films and monolayers
      are studied by temperature-resolved grazing-incidence X-ray diffraction and
      scanning force microscopy. The interplay between H-bonding and ordering of the
      alkyl chains results in a rich temperature-dependent phase behavior. The
      monodendrons form H-bonded stabilized clusters with the number of molecules
      depending on the length of the aliphatic chains and temperature. The clusters
      play the role of constitutive units in the subsequent self-assembly. Short alkyl
      chains allow the material to form thermodynamically stable crystalline phases.
      The molecules with longer side groups exhibit additional transitions from the
      crystalline phase to thermotropic columnar hexagonal or columnar rectangular
      liquid-crystalline phases. In monolayers deposited on highly ordered pyrolytic
      graphite, the materials show ordering similar to thin films. However, for the
      compound bearing hexadecyl chains the affinity of the alkyl groups to graphite
      dominates the self-assembly and thereby allows epitaxial growth of a 2D lattice
      with flat-on oriented molecules.

PMID- 22407508
TI  - Phase transfer catalyzed enantioselective cyclopropanation of 4-nitro-5
      styrylisoxazoles.
AB  - Heavily substituted cyclopropane esters were prepared in high yields, complete
      diastereoselection and high (up to 96%) enantioselectivity. The reaction
      described herein entailed reacting 4-nitro-5-styrylisoxazoles, a class of
      cinnamate synthetic equivalent, with 2-bromomalonate esters under the catalysis
      of 5 mol% of a Cincona derived phase-transfer catalyst. The reaction allowed
      multi-gram preparation of desired products.

PMID- 22407507
TI  - Poncirin prevents bone loss in glucocorticoid-induced osteoporosis in vivo and in
      vitro.
AB  - Poncirin, a flavonoid isolated from the fruit of Poncirus trifoliata, possesses
      anti-bacterial and anti-inflammatory activities. However, the action of poncirin
      in bone biology is unclear. In this study, the in vivo and in vitro effects of
      poncirin in a glucocorticoid-induced osteoporosis (GIO) mouse model were
      investigated. Seven-month-old male mice were assigned to the following five
      groups: (1) sham-implantation (sham), (2) prednisolone 2.1 mg/kg/day (GC), (3) GC
      treated with 10 mg/kg/day of genistein, (4) GC treated with 3 mg/kg/day of
      poncirin, (5) and GC treated with 10 mg/kg/day of strontium (GC + SrCl(2)). After
      8 weeks, bone loss was measured by microcomputed tomography. Osteocalcin (OC) and
      C-terminal telopeptides of type I collagen (CTX) were evaluated in sera. Runx2
      protein, OC and osteoprotegerin (OPG) mRNA expression, alkaline phosphatase (ALP)
      activity, and mineral nodule assay were performed in C3H10T1/2 or primary bone
      marrow stromal cells. Poncirin significantly increased the bone mineral density
      and improved the microarchitecture. Poncirin increased serum OC, Runx2 protein
      production, expression of OC and OPG mRNA, ALP activity, and mineral nodule
      formation; and decreased serum CTX. These effects were more prominent in the
      poncirin group compared to the other positive control groups (genistein and
      strontium). The poncirin-mediated restoration of biochemical bone markers,
      increased bone mineral density, and improved trabecular microarchitecture likely
      reflect increased bone formation and decreased bone resorption in GIO mice.

PMID- 22407509
TI  - A cross-sectional analysis of the cognitive model of bulimia nervosa.
AB  - OBJECTIVE: The present study aimed to directly test Cooper et al.'s cognitive
      model of the maintenance of bulimia nervosa. METHOD: The major predictions of the
      model were tested cross-sectionally using multiple regression analyses and
      structural equation modeling in a mixed sample comprising nonclinical female
      university students (n = 298) and clinical eating disorder patients (n = 44).
      RESULTS: Consistent with model, negative self-beliefs was associated with
      negative emotion, negative emotion with positive and negative beliefs about
      eating, beliefs about eating with eating behavior, and binge eating with negative
      self-beliefs. However, contrary to hypotheses, results did not consistently
      support a direct link between compensatory behavior and negative self-beliefs.
      Furthermore, the role of permissive thoughts was found to be questionable. Of
      note, results suggested that components of the model may operate to maintain
      bulimic pathology in a slightly different way for purging and nonpurging
      behaviors. DISCUSSION: While the results of this research provide some
      preliminary evidence for the validity of the cognitive model as an explanation of
      the persistence of bulimic symptoms, further work is required to develop the
      model.

PMID- 22407510
TI  - A multicenter randomized placebo-controlled clinical trial of pramipexole for
      Tourette's syndrome.
AB  - BACKGROUND: Dopamine agonists could theoretically normalize the suspected central
      dopamine hypersensitivity in Tourette's syndrome. METHODS: There was a
      multicenter randomized, placebo-controlled, double-blind clinical trial of
      pramipexole given for 6 weeks in 63 children and adolescents with Tourette's
      syndrome. RESULTS: There were no significant differences in the adjusted mean
      change in the Total Tic Score of the Yale Global Tic Severity Scale for patients
      treated with pramipexole (-7.16) and placebo (-7.17). There were no significant
      treatment effects on change from baseline in the Global Severity score of the
      Yale Scale and parent- and investigator-scored Clinical Global Impression of
      Improvement. In patients with attention deficit hyperactivity disorder, there was
      improvement in DuPaul ADHD scale scores for patients receiving pramipexole
      compared with placebo. CONCLUSIONS: There was no evidence that pramipexole has
      efficacy in suppressing tics. Pramipexole may decrease symptoms of associated
      attention deficit hyperactivity disorder.

PMID- 22407511
TI  - [Health services research on paranasal sinus surgery in Thuringia: epidemiologic
      key data and outcome].
AB  - BACKGROUND: Although modern minimal-invasive paranasal sinus surgery is an
      integral part of clinical routine of otorhinolaryngologic surgeons, there are no
      population-based data on incidence and efficiency of this surgery published.
      MATERIAL AND METHODS: 1,582 patients underwent paranasal sinus surgery in the 8
      Thuringian departments of otorhinolaryngology in 2005. All patients were analysed
      regarding patients' characteristics, therapy, complications and further course of
      disease. RESULTS: The incidence of paranasal sinus surgery was 46/100,000 for
      women and higher for men with 72/100,000. Median age was 48 years. Chronic
      sinusitis was the main reason for surgery (94%; including 33% with nasal polyps)
      and was performed dominantly as endoscopic sinus surgery (96%). Surgery was
      performed bilaterally in 75% of the cases and as primary surgery. In most cases
      at least 2 paranasal sinuses per side were approached. Relevant complications
      were observed in 4% of patients. During the follow-up time of 45-51 months a
      recurrence was observed in 9% of cases. Using a multivariate regression analysis,
      revision surgery, allergic subject and diagnosis of a malignant tumor were
      significant independent risk factors to predict a recurrence. Older age and
      longer time of surgery were significant independent risk factors for a
      complication. CONCLUSION: This population based analysis is showing that modern
      paranasal sinus surgery is performed in high incidence, effectively and with low
      risk on a large scale in daily routine of rhinologic surgeons.

PMID- 22407512
TI  - [A rare complication of acute sinusitis].

PMID- 22407513
TI  - Terminal costs, improved life expectancy and future public health expenditure.
AB  - This paper presents an empirical analysis of public health expenditure on
      individuals in Denmark. The analysis separates out the individual effects of age
      and proximity to death (reflecting terminal costs of dying) and employs unique
      micro data from the period 2000 to 2009, covering a random sample of 10% of the
      Danish population. Health expenditure includes treatment in hospitals, subsidies
      to prescribed medication and health care provided by general practitioners and
      specialists and covers about 80% of public health care expenditure on
      individuals. The results confirm findings from previous studies showing that
      proximity to death has a significant impact on health care expenditure. However,
      it is also found that cohort effects (the baby boom generation) as well as
      improvements in life expectancy have a substantial effect on future health care
      expenditure even when proximity to death is controlled for. These results are
      obtained by combining the empirical estimates with a long term population
      forecast. When life expectancy increases, terminal costs are postponed but the
      increases in health expenditure that follow from longer life expectancy are not
      as large as the increase in the number of elderly persons would suggest (due to
      "healthy ageing"). Based on the empirical estimates, healthy ageing is expected
      to reduce the impact of increased life expectancy on real health expenditure by
      50% compared to a situation without healthy ageing.

PMID- 22407514
TI  - Aluminium phosphide poisoning and oxidative stress: serum biomarker assessment.
AB  - According to previous animal studies, aluminium phosphides (AlPs) may induce
      oxidative stress leading to generation of free radicals and alteration in
      antioxidant defense system. This study was conducted to evaluate the existence
      and degree of oxidative stress in patients with acute AlP ingestion. A total of
      44 acute AlP ingested patients as well as 44 age- and sex-matched controls were
      included. All patients had acute poisoning symptoms with AlP at the time of
      presentation and had blood samples analyzed for lipid peroxidation, total
      antioxidant capacity and total thiol. Our findings showed that there is a
      significant increase in lipid peroxidation in AlP ingested group along with a
      reduction in total antioxidant capacity and total thiols groups. These clinical
      data confirm previous experimental models that showed AlP exposure might
      significantly augment lipoperoxidative damage with simultaneous alterations in
      the antioxidant defense system. Hence, our findings might justify use of
      antioxidants in treatment of acute AlP poisoning which needs to be clarified by
      additional clinical trials.

PMID- 22407515
TI  - Renal embolic protection devices improve blood flow after stenting for
      atherosclerotic renal artery stenosis.
AB  - OBJECTIVES: We sought to measure angiographic renal frame counts (RFC), as a
      quantitative angiographic assessment of renal blood flow, to evaluate
      microvascular compromise due to atheroembolism associated with RAS. BACKGROUND:
      Atheroembolism associated with renal artery stenting (RAS) has been implicated as
      a cause for worsening renal function following successful intervention. Use of a
      distal embolic protection device (EPD) during RAS has been shown to be safe with
      debris capture in a high percentage of cases. However, objective benefit for
      renal function with EPD has been difficult to demonstrate. METHODS: A control
      group of 30 consecutive patients (33 kidneys) who underwent RAS without EPD were
      compared with 33 consecutive patients (33 kidneys) who underwent RAS with EPD
      using RFC measurement. RESULTS: The prestent and poststent mean RFC for the
      control group was 30.4 +/- 12.1 vs. 23.7 +/- 9.9 (P = 0.002) and for the EPD
      group it was 42.6 +/- 12.6 vs. 28.3 +/- 9.2 (P < 0.0001). The EPD group had a
      greater improvement in renal blood flow, manifested by a greater reduction of the
      RFC (Delta RFC) 14.2 +/- 15.2 vs. 6.7 +/- 11.7 (P = 0.03) compared with the
      control group. CONCLUSIONS: The use of an EPD was associated with a much larger
      improvement in renal blood flow (lower RFC) following RAS. This suggests that
      EPD's may be effective in preventing renal atheroembolic injury and that a
      controlled trial measuring the impact of EPD's on renal blood flow following RAS
      should be performed.

PMID- 22407516
TI  - Structurally diverse MU-conotoxin PIIIA isomers block sodium channel NaV 1.4.

PMID- 22407517
TI  - Impact of the carbazole derivative wiskostatin on mechanical stability and
      dynamics of motile cells.
AB  - Many essential functions in eukaryotic cells like phagocytosis, division, and
      motility rely on the dynamical properties of the actin cytoskeleton. A central
      player in the actin system is the Arp2/3 complex. Its activity is controlled by
      members of the WASP (Wiskott-Aldrich syndrome protein) family. In this work, we
      investigated the effect of the carbazole derivative wiskostatin, a recently
      identified N-WASP inhibitor, on actin-driven processes in motile cells of the
      social ameba Dictyostelium discoideum. Drug-treated cells exhibited an altered
      morphology and strongly reduced pseudopod formation. However, TIRF microscopy
      images revealed that the overall cortical network structure remained intact. We
      probed the mechanical stability of wiskostatin-treated cells using a microfluidic
      device. While the total amount of F-actin in the cells remained constant, their
      stiffness was strongly reduced. Furthermore, wiskostatin treatment enhanced the
      resistance to fluid shear stress, while spontaneous motility as well as
      chemotactic motion in gradients of cAMP were reduced. Our results suggest that
      wiskostatin affects the mechanical integrity of the actin cortex so that its
      rigidity is reduced and actin-driven force generation is impaired.

PMID- 22407518
TI  - A large-area light-weight dye-sensitized solar cell based on all titanium
      substrates with an efficiency of 6.69% outdoors.
AB  - Light-weight PEDOT-Pt/Ti mesh and Ti/TiO(2)  foil electrodes are prepared. Owing
      to the PEDOT-Pt/Ti photocathode's high transparency, good electrocatalytic
      activity, and low resistance; the Ti/TiO(2)  anode's large specific area and high
      conductivity, a light-weight backside illuminated large-area (100 cm(2) ) dye
      sensitized solar cell achieves an energy conversion efficiency of 6.69% under an
      outdoors sunlight irradiation of 55 mW cm(-2) .

PMID- 22407519
TI  - Single-walled carbon nanotubes as scaffolds to concentrate DNA for the study of
      DNA-protein interactions.
AB  - Genomic DNA in bacteria exists in a condensed state, which exhibits different
      biochemical and biophysical properties from a dilute solution. DNA was
      concentrated on streptavidin-covered single-walled carbon nanotubes (Strep-SWNTs)
      through biotin-streptavidin interactions. We reasoned that confining DNA within a
      defined space through mechanical constraints, rather than by manipulating buffer
      conditions, would more closely resemble physiological conditions. By ensuring a
      high streptavidin loading on SWNTs of about 1 streptavidin tetramer per 4 nm of
      SWNT, we were able to achieve dense DNA binding. DNA is bound to Strep-SWNTs at a
      tunable density and up to as high as 0.5 mg mL(-1) in solution and 29 mg mL(-1)
      on a 2D surface. This platform allows us to observe the aggregation behavior of
      DNA at high concentrations and the counteracting effects of HU protein (a histone
      like protein from Escherichia coli strain U93) on the DNA aggregates. This
      provides an in vitro model for studying DNA-DNA and DNA-protein interactions at a
      high DNA concentration.

PMID- 22407520
TI  - Lifestyle change and high-density lipoprotein change: the US Department of
      Veterans Affairs Normative Aging Study.
AB  - BACKGROUND: We sought to determine whether lifestyle modifications are associated
      with high-density lipoprotein cholesterol (HDL-C) change in a cohort with long
      term follow-up. HYPOTHESIS: Changes in alcohol consumption, smoking, or body mass
      index (BMI) are associated with within-individual changes in HDL-C. METHODS: We
      selected 1420 men with >=2 HDL-C measurements from the US Department of Veterans
      Affairs Normative Aging Study (NAS). Changes in HDL-C (in milligrams/deciliter)
      over a 3-year period were calculated for each pair of exams. For each interval of
      HDL-C change, lifestyle exposures were categorized: participants maintained a
      stable BMI >25 kg/m(2) (reference) or <=25 kg/m(2) since the previous exam, or
      increased or decreased BMI; participants were actively smoking at both exams
      (reference), nonsmokers at both exams, quit, or initiated smoking between exams;
      and participants maintained alcohol intake of <2 (reference) or >=2 drinks daily
      since the previous exam, or increased or decreased alcohol intake. Longitudinal
      analysis was used to examine the relationship between the lifestyle change
      categories and 3-year change in HDL-C for each interval, adjusting for
      comorbidities, lipids, and cholesterol medication. RESULTS: Participants were
      followed for approximately 14.3 years. Increases in HDL-C were associated with
      maintaining alcohol intake of >=2 drinks daily (mean HDL-C increase, 0.86; P =
      0.02), increasing alcohol intake from <2 to >=2 drinks daily (mean, 2.53; P =
      0.0003), and with maintaining a BMI of <=25 kg/m(2) (mean, 0.71; P = 0.04).
      CONCLUSIONS: Increases in alcohol consumption, maintaining moderate alcohol
      intake, and maintaining BMI <=25 kg/m(2) were associated with significant 3-year
      increases in HDL-C.

PMID- 22407521
TI  - Phenomenology of psychogenic movement disorders in children.
AB  - Psychogenic movement disorders are heterogeneous and diagnostically challenging.
      Despite the growing literature on adult forms, clinical features in children have
      received relatively little attention. We retrospectively reviewed medical records
      and video of patients <18 years diagnosed with a psychogenic movement disorder at
      our institute between 2007 and 2010. We identified 14 patients (6 males and 8
      females) with a mean onset age of 11.5 years. Levels of diagnostic confidence
      were documented (2 patients), clinically established (8 patients), and probable
      (4 patients). A single movement disorder was present in 10 patients (71%); 4
      patients (29%) presented an association of two or more movement disorders. Eleven
      patients presented other medically unexplained symptoms associated with their
      movement disorders. Five patients, among 6 with chronic occurrence, performed a
      polymyographic study showing significant modifications of frequency, amplitude,
      and distribution of electromyographic activity, related to distracting maneuvers.
      The present series represents 5% of all movement disorders observed in the
      considered period and 32% of nonorganic neurological manifestations. The most
      frequent movement disorders were tremor (36%) and dystonia (29%). We describe two
      phenotypes not previously reported among psychogenic movement disorders:
      myoclonus and association of myoclonus with dystonia. We remark on the presence
      of psychogenic symptoms associated with movement disorders (79%) as being one of
      the most useful clinical clues as well as on the value of polymyographic study in
      chronic psychogenic movement disorders, which provide evidence of the
      inconsistency of movement disorders.

PMID- 22407522
TI  - The effects of substrate stiffness on the in vitro activation of macrophages and
      in vivo host response to poly(ethylene glycol)-based hydrogels.
AB  - Poly(ethylene glycol) (PEG) hydrogels, modified with RGD, are promising platforms
      for cell encapsulation and tissue engineering. While these hydrogels offer
      tunable mechanical properties, the extent of the host response may limit their in
      vivo applicability. The overall objective was to characterize the effects of
      hydrogel stiffness on the in vitro macrophage response and in vivo host response.
      We hypothesized that stiffer substrates induce better attachment, adhesion, and
      increased cell spreading, which elevates the macrophage classically activated
      phenotype and leads to a more severe foreign body reaction (FBR). PEG-RGD
      hydrogels were fabricated with compressive moduli of 130, 240, and 840 kPa, and
      the same RGD concentration. Hydrogel stiffness did not impact macrophage
      attachment, but elicited differences in cell morphology. Cells retained a round
      morphology on 130 kPa substrates, with localized and dense F-actin and localized
      alpha(V) integrin stainings. Contrarily, cells on stiffer substrates were more
      spread, with filopodia protruding from the cell, a more defined F-actin, and
      greater alpha(V) integrin staining. When stimulated with lipopolysaccharide,
      macrophages had a classical activation phenotype, with increased expression of
      TNF-alpha, IL-1beta, and IL-6, however the degree of activation was significantly
      reduced with the softest hydrogels. A FBR ensued in response to all hydrogels
      when implanted subcutaneously in mice, but 28 days postimplantation the layer of
      macrophages at the implant surface was significantly lower in the softest
      hydrogels. In conclusion, hydrogels with lower stiffness led to reduced
      macrophage activation and a less severe and more typical FBR, and therefore are
      more suited for in vivo tissue engineering applications.

PMID- 22407523
TI  - Short polyglutamine peptide forms a high-affinity binding site for thioflavin-T
      at the N-terminus.
AB  - Thioflavin-T is one of the most important amyloid specific dyes and has been used
      for more than 50 years; however, the molecular mechanism of staining is still not
      understood. Chemically synthesized short polyglutamine peptides (Q(n), n = 5-10)
      were subjected to the thioflavin-T (ThT) staining assay. It was found that the
      minimum Q(n) peptide that stained positive to ThT was Q(6). Two types of ThT
      binding sites, a high-affinity site (k(d1) = 0.1-0.17 MUM) and a low-affinity
      site (k(d2) = 5.7-7.4 MUM), were observed in short polyQs (n = 6-9).
      (13)C{(2)H}REDOR NMR experiments were carried out to extract the local structure
      of ThT binding sites in Q(8) peptide aggregates by observing the intermolecular
      dipolar coupling between [3-Me-d(3)]ThT and natural abundance Q(8) or residue
      specific [1,2-(13)C(2)] labeled Q(8)s. (13)C{(2)H}REDOR difference spectra of the
      [3-Me-d(3)]ThT/natural abundance Q(8) (1/9) complex indicated that all of the
      five carbons of the glutamine residue participated in the formation of ThT
      binding sites. (13)C{(2)H}DQF-REDOR experiments of [3-Me-d(3)]ThT/residue
      specific [1,2-(13)C(2)] labeled Q(8) (1/50) complexes demonstrated that the N
      terminal glutamine residue had direct contact with the ThT molecule at the high
      affinity ThT-binding sites.

PMID- 22407524
TI  - Glenoid cartilage mechanical properties decrease after rotator cuff tears in a
      rat model.
AB  - Rotator cuff repairs are commonly performed to reduce pain and restore function.
      Tears are also treated successfully without surgical intervention; however, the
      effect that a torn tendon has on the glenohumeral cartilage remains unknown.
      Clinically, a correlation between massive rotator cuff tears and glenohumeral
      arthritis has often been observed. This may be due to a disruption in the balance
      of forces at the shoulder, resulting in migration of the humeral head and
      subsequently, abnormal loading of the glenoid. Our lab previously demonstrated
      changes in ambulation and intact tendon mechanical properties following
      supraspinatus and infraspinatus rotator cuff tendon tears in a rat model.
      Therefore, the purpose of this study was to investigate the effects of
      supraspinatus and infraspinatus rotator cuff tears on the glenoid cartilage. Nine
      rats underwent unilateral detachment of the supraspinatus and infraspinatus
      tendons and were sacrificed after 4 weeks. Cartilage thickness significantly
      decreased in the antero-inferior region of injured shoulders. In addition,
      equilibrium elastic modulus significantly decreased in the center, antero
      superior, antero-inferior, and superior regions. These results suggest that
      altered loading after rotator cuff injury may lead to damage to the joint with
      significant pain and dysfunction. Clinically, understanding the mechanical
      processes involved with joint damage will allow physicians to better advise
      patients.

PMID- 22407525
TI  - Diastereo- and enantioselective intramolecular C(sp3)-H arylation for the
      synthesis of fused cyclopentanes.
AB  - All C-H bonds are not equal: The intramolecular arylation of unactivated C(sp(3))
      H bonds in the presence of a chiral Pd/binepine catalyst allows the synthesis of
      fused cyclopentanes efficiently and in an diastereo- and enantioselective manner
      (see scheme).

PMID- 22407526
TI  - Japanese encephalitis and Japanese encephalitis virus in mainland China.
AB  - Japanese encephalitis (JE), caused by Japanese encephalitis virus (JEV)
      infection, is the most important viral encephalitis in the world. Approximately
      35,000-50,000 people suffer from JE every year, with a mortality rate of 10,000
      15,000 people per year. Although the safety and efficacy of JE vaccines
      (inactivated and attenuated) have been demonstrated, China still accounts for 50%
      of the reported JE cases worldwide. In this review, we provide information about
      the burden of JE in mainland China and the corresponding epidemiology from 1949
      to 2010, including the morbidity and mortality of JE; the age, gender, and
      vocational distribution of JE cases; its regional and seasonal distribution; and
      JE immunization. In addition, we discuss the relationships among vectors, hosts,
      and JEV isolates from mainland China; the dominant vector species for JEV
      transmission; the variety of JEV genotypes and the different biological
      characteristics of the different JEV genotypes; and the molecular evolution of
      JEV.

PMID- 22407527
TI  - [Helpful factors in day treatment for alcohol dependent patients--a qualitative
      narrative interview approach].
AB  - Day treatment for alcohol dependent patients is still uncommon in Germany. The
      presented study aims to answer the question how patients experience this kind of
      treatment and which factors they perceive as important for their treatment
      success.7 interviews with alcohol-dependent patients were conducted. Data were
      analysed with qualitative methods and the help of a computer-supported coding
      system.We found several factors that are relevant for patients, especially
      important are factors concerning the therapeutical relationship as well as
      factors that are specific for day treatment.We can conclude that day treatment is
      seen as helpful to improve dependency symptoms by the patients.

PMID- 22407528
TI  - [Steadfast--effectiveness of a cognitive-behavioral self-management program for
      patients with somatoform vertigo and dizziness].
AB  - The aim of the study was to evaluate a psychotherapeutic intervention for
      somatoform vertigo regarding illness perception, severity and
      psychopathology.Patients underwent a waiting-list control group design (n=10
      control group; n=14 intervention group with diagnostics at baseline, post
      intervention, 3- and 12-month follow-up). Psychometric assessments comprised the
      Illness Perception Questionnaire, Vertigo Symptom and Handicap Questionnaire,
      Hospital Anxiety and Depression Scale, and Physical Health Questionnaire.The
      intervention group improved in personal control (p=0.046; d=0.46), and coherency
      (p=0.087; d=0.42). Illness beliefs in organic deteriorations could be corrected
      towards psychosomatic attributions.Steadfast decreased dysfunctional illness
      representations and increased patient empowerment.

PMID- 22407529
TI  - [Body psychotherapy at the university--a needs assessment at psychosomatic
      clinics supports the installment of the first German study major in body
      psychotherapy].
AB  - As part of the accreditation process of a study major in Body Psychotherapy (BPT)
      at the University of Marburg, a needs analysis at 74 German Psychosomatic Clinics
      was conducted. Objective of the analysis was to assess the importance of body
      psychotherapy in psychosomatic clinics and to inquire about a demand for
      therapists with a University Masters Degree in body psychotherapy. Almost two
      thirds (61.3%) of the participating 31 chief physicians valued body psychotherapy
      as "very important" to their treatment program and 77.4% stated a hiring
      preference for a therapist with a Masters Degree in BPT. These positive results
      supported the creation of the study major BPT in question, which is open to
      students since Winter Semester 2010/11.

PMID- 22407530
TI  - Bilateral skin conductance responses to emotional faces.
AB  - Skin conductance responses (SCR) measure objective arousal in response to
      emotionally-relevant stimuli. Central nervous system influence on SCR is exerted
      differentially by the two hemispheres. Differences between SCR recordings from
      the left and right hands may therefore be expected. This study focused on
      emotionally expressive faces, known to be processed differently by the two
      hemispheres. Faces depicting neutral, happy, sad, angry, fearful or disgusted
      expressions were presented in two tasks, one with an explicit emotion judgment
      and the other with an age judgment. We found stronger responses to sad and happy
      faces compared with neutral from the left hand during the implicit task, and
      stronger responses to negative emotions compared with neutral from the right hand
      during the explicit task. Our results suggest that basic social stimuli generate
      distinct responses on the two hands, no doubt related to the lateralization of
      social function in the brain.

PMID- 22407531
TI  - The impact of relationships on the association between sexual orientation and
      disordered eating in men.
AB  - OBJECTIVE: Robust evidence supports that bisexual and gay (BG) men have increased
      eating pathology compared to heterosexual men. BG men may be at greater risk due
      to pressure to attract a male partner; however, the related implication that
      relationships serve as protective factors for BG men remains untested. METHOD: BG
      (n = 42) and heterosexual men (n = 536) completed surveys to determine whether
      relationship status and satisfaction moderate sexual orientation's effect on
      disordered eating. RESULTS: Single BG men had increased restrictive disordered
      eating compared to single heterosexual men, while few differences were found
      between BG and heterosexual men in relationships. Relationship satisfaction was
      not related to restrictive disordered eating; however, low relationship
      satisfaction was associated with increased bulimic symptomatology in BG men
      compared to heterosexual men. DISCUSSION: Being in a relationship, independent of
      whether or not the relationship is satisfying, may be a protective factor for
      restrictive disordered eating in BG men.

PMID- 22407532
TI  - Long-term adaptation of the human lung tumor cell line A549 to increasing
      concentrations of hydrogen peroxide.
AB  - Previously, we demonstrated that A549, a human lung cancer cell line, could be
      adapted to the free radical nitric oxide (NO?). NO? is known to be over expressed
      in human tumors. The original cell line, A549 (parent), and the newly adapted
      A549-HNO (which has a more aggressive phenotype) serve as a useful model system
      to study the biology of NO?. To see if tumor cells can similarly be adapted to
      any free radical with the same outcome, herein we successfully adapted A549 cells
      to high levels of hydrogen peroxide (HHP). A549-HHP, the resulting cell line, was
      more resistant and grew better then the parent cell line, and showed the
      following characteristics: (1) resistance to hydrogen peroxide, (2) resistance to
      NO?, (3) growth with and without hydrogen peroxide, and (4) resistance to
      doxorubicin. Gene chip analysis was used to determine the global gene expression
      changes between A549-parent and A549-HHP and revealed significant changes in the
      expression of over 1,700 genes. This gene profile was markedly different from
      that obtained from the A549-HNO cell line. The mitochondrial DNA content of the
      A549-HHP line determined by quantitative PCR favored a change for a more
      anaerobic metabolic profile. Our findings suggest that any free radical can
      induce resistance to other free radicals; this is especially important given that
      radiation therapy and many chemotherapeutic agents exert their effect via free
      radicals. Utilizing this model system to better understand the role of free
      radicals in tumor biology will help to develop new therapeutic approaches to
      treat lung cancer.

PMID- 22407533
TI  - RNA interference of hypoxia-inducible factor-1 alpha improves the effects of
      transcatheter arterial embolization in rat liver tumors.
AB  - Transcatheter arterial embolization (TAE) and transcatheter arterial
      chemoembolization are widely used palliative treatments for patients with
      nonsurgical hepatocellular carcinoma. TAE has been shown to increase levels of
      hypoxia-inducible factor-1 alpha (HIF-1alpha) in tumors. In this study, we
      investigated whether RNA interference (RNAi) of HIF-1alpha could improve the
      efficacy of TAE to treat HCC. Four treatment groups were assessed using a rat
      allograft model of HCC: RNAi of HIF-1alpha combined with TAE, RNAi of HIF-1alpha
      only, TAE only, and a control group. Rats were treated by TAE by retrograde
      placement of a microcatheter into the gastroduodenal artery. The results
      demonstrated that the RNAi of HIF-1alpha visibly reduced the expression of HIF
      1alpha and vascular endothelial growth factor, suppressed tumor angiogenesis, and
      attenuated metastasis, which were all enhanced by TAE. The RNAi of HIF-1alpha
      synergized with TAE to significantly inhibit tumor growth. In conclusion, RNAi of
      HIF-1alpha augmented the therapeutic effects of TAE and diminished its
      undesirable effects.

PMID- 22407534
TI  - Bilateral oculomotor synkinesis following Miller Fisher syndrome.
AB  - A 64-year-old female presented with ptosis, ophthalmoplegia, ataxia, and
      weakness. She was diagnosed with Miller Fisher syndrome (MFS) and was treated
      with plasmapheresis. Six months later, she developed bilateral oculomotor
      synkinesis, suggesting aberrant regeneration. The pathogenesis of MFS is reviewed
      in light of this unusual finding.

PMID- 22407535
TI  - Optimisation of a capillary zone electrophoresis methodology for simultaneous
      analysis of organic aliphatic acids in extracts of Brachiaria brizantha.
AB  - INTRODUCTION: Aluminum toxicity is commonly verified in acidic soils, and poses a
      severe limitation to plant growth and development. Therefore, Al complexation by
      the root system mucilage, Al complexation by organic compounds that are exuded by
      the roots and internal metabolic processes must be monitored by organic acids
      (OA), since they play a central role in these aluminum tolerance mechanisms.
      OBJECTIVE: To optimise a capillary zone electrophoresis method able to perform
      simultaneous separation of acetic, citric, formic, lactic, malic, oxalic,
      pyruvic, succinic, tartaric and aspartic acid in plant extract solutions.
      METHODOLOGY: Method optimisation was achieved by a chemometric approach through
      experimental designs. The optimal condition found was: 20 mmol/L phthalic acid
      buffer; 0.8 mmol/L cetyltrimethyl-ammonium bromide; pH 3.4 adjusted with
      tris(hydroxymethyl)aminomethane (around 16 mmol/L); -15 kV of voltage; 25 
      degrees C of cartridge temperature; indirect ultraviolet detection at 240 nm; and
      25 mbar injection for 2 s, within an analysis time of 4 min. RESULTS: As a
      repeatability test of the optimal condition, 30 replicates were carried out with
      the same working electrolyte, where the relative standard deviation of each peak
      ranged from 0.081 to 0.36% (for migration time) and from 2.4 to 4.6% (for peak
      area). CONCLUSION: The methodology was successfully applied to simultaneously
      determine citric, malic and aspartic acid in roots and leaves extract solutions
      of Brachiaria brizantha, demonstrating its usefulness to study aluminum
      tolerance.

PMID- 22407536
TI  - Regression analysis based on conditional likelihood approach under semi-competing
      risks data.
AB  - Medical studies often involve semi-competing risks data, which consist of two
      types of events, namely terminal event and non-terminal event. Because the non
      terminal event may be dependently censored by the terminal event, it is not
      possible to make inference on the non-terminal event without extra assumptions.
      Therefore, this study assumes that the dependence structure on the non-terminal
      event and the terminal event follows a copula model, and lets the marginal
      regression models of the non-terminal event and the terminal event both follow
      time-varying effect models. This study uses a conditional likelihood approach to
      estimate the time-varying coefficient of the non-terminal event, and proves the
      large sample properties of the proposed estimator. Simulation studies show that
      the proposed estimator performs well. This study also uses the proposed method to
      analyze AIDS Clinical Trial Group (ACTG 320).

PMID- 22407537
TI  - Reversible ON/OFF nanoswitch for organocatalysis: mimicking the locking and
      unlocking operation of CaMKII.
AB  - Flip a switch: a nanoswitch uses chemical inputs to turn an organocatalytic
      Knoevenagel reaction on and off (see scheme: R=reactant, P=product). To stop
      catalysis the chemical input (pink and green) wraps around the inhibitory segment
      of the nanoswitch to effect release or unlocking of the switch. The process can
      run reversibly over three cycles without loss of activity.

PMID- 22407538
TI  - Mesoporous block copolymer nanoparticles with tailored structures by hydrogen
      bonding-assisted self-assembly.
AB  - A simple, yet robust route to prepare polymer nanoparticles with tunable internal
      structures through supramolecular assembly within emulsion droplets is presented.
      Nanoparticles with various internal morphologies, including dispersed spheres,
      dispersed spirals, stacked toroids, and concentric lamellae, are obtained due to
      the 3D confinement and variation of hydrogen-bonding agent. This method also
      allows us to form mesoporous particles through further disassembly of the
      supramoleclar assemblies by rupturing the hydrogen bonding.

PMID- 22407539
TI  - Role of gonadal hormones in programming developmental changes in thymopoietic
      efficiency and sexual diergism in thymopoiesis.
AB  - There is a growing body of evidence indicating the important role of the neonatal
      steroid milieu in programming sexually diergic changes in thymopoietic
      efficiency, which in rodents occur around puberty and lead to a substantial
      phenotypic and functional remodeling of the peripheral T-cell compartment. This
      in turn leads to an alteration in the susceptibility to infection and various
      immunologically mediated pathologies. Our laboratory has explored interdependence
      in the programming and development of the hypothalamo-pituitary-gonadal axis and
      thymus using experimental model of neonatal androgenization. We have outlined
      critical points in the complex process of T-cell development depending on
      neonatal androgen imprinting and the peripheral outcome of these changes and have
      pointed to underlying mechanisms. Our research has particularly contributed to an
      understanding of the putative role of changes in catecholamine-mediated
      communications in the thymopoietic alterations in adult neonatally androgenized
      rats.

PMID- 22407540
TI  - Rapid methods of detecting the target molecule in immunohistology using a
      bioluminescence probe.
AB  - We demonstrate a novel rapid direct detection method for immunohistochemistry,
      using a bioluminescent probe. An anti-CEA antibody-fused far-red bioluminescent
      protein can monitor the accumulation of this type of probe in tumour tissues. The
      bimodal spectrum (lambda(max) = 460 and 675 nm) of this bioluminescent probe is
      extremely stable under different conditions of pH and ion concentration. The
      sensitivity of our bioluminescent labelling was at the same level of enzymatic
      labelling, e.g. peroxidase, as an indirect system. Our novel technique is simple
      and can shorten the pretreatment time of paraffin sections to around 30 min. The
      utility of our bioluminescent labelling covers all imaging in vitro, in vivo and
      ex vivo, suggesting that our antibody-fused bioluminescent probe has the
      potential to detect tumour antigens with a high sensitivity in routine immune
      histological examinations.

PMID- 22407541
TI  - The collagenolytic action of MMP-1 is regulated by the interaction between the
      catalytic domain and the hinge region.
AB  - The role of the hinge region in the unwinding and cleavage of type I collagen by
      interstitial collagenase (MMP-1) has been studied at 37  degrees C and pH 7.3.
      The collagenolytic processing by MMP-1 displays a very similar overall rate for
      both chains of collagen I, even though the affinity is higher for the alpha-1
      chain and the cleavage rate is faster for the alpha-2 chain. MMP-1 binding to
      collagen I brings about a significant unwinding of the triple-helical arrangement
      only after the first cleavage step of the alpha-1 and alpha-2 chains. The
      proteolytic processing by wild-type MMP-1 on a synthetic substrate and collagen I
      has been compared with that observed for site-directed mutants obtained either by
      truncating the hinge region (?255-272) or by individually replacing the conserved
      amino acids Val268, Gly272, and Lys277 of the hinge region with residues observed
      for the corresponding position in stromelysin-1 (MMP-3), a noncollagenolytic
      metalloproteinase. The ?256-272 mutant has no collagenolytic activity, clearly
      demonstrating the crucial role of this region for the enzymatic processing of
      collagen I. However, among various mutants investigated, only Gly272Asp shows a
      dramatically reduced enzymatic activity both on the synthetic substrate and on
      collagen I. This effect, however, is clearly related to the substituting residue,
      since substitution of Ala or Asn for Gly272 does not have any effect on the
      kinetic properties of MMP-1. These data suggest that the substrate specificity of
      MMP-1 is dictated by the reciprocal structural relationships between the
      catalytic domain and the carboxy-terminal domain through the conformational
      arrangement of the hinge region.

PMID- 22407542
TI  - Role of an isoform-specific serine residue in FMN-heme electron transfer in
      inducible nitric oxide synthase.
AB  - In the crystal structure of a calmodulin (CaM)-bound FMN domain of human
      inducible nitric oxide synthase (NOS), the CaM-binding region together with CaM
      forms a hinge, and pivots on an R536(NOS)/E47(CaM) pair (Xia et al. J Biol Chem
      284:30708-30717, 2009). Notably, isoform-specific human inducible NOS S562 and
      C563 residues form hydrogen bonds with the R536 residue through their backbone
      oxygens. In this study, we investigated the roles of the S562 and C563 residues
      in the NOS FMN-heme interdomain electron transfer (IET), the rates of which can
      be used to probe the interdomain FMN/heme alignment. Human inducible NOS S562K
      and C563R mutants of an oxygenase/FMN (oxyFMN) construct were made by introducing
      charged residues at these sites as found in human neuronal NOS and endothelial
      NOS isoforms, respectively. The IET rate constant of the S562K mutant is notably
      decreased by one third, and its flavin fluorescence intensity per micromole per
      liter is diminished by approximately 24 %. These results suggest that a positive
      charge at position 562 destabilizes the hydrogen-bond-mediated NOS/CaM alignment,
      resulting in slower FMN-heme IET in the mutant. On the other hand, the IET rate
      constant of the C563R mutant is similar to that of the wild-type, indicating that
      the mutational effect is site-specific. Moreover, the human inducible NOS oxyFMN
      R536E mutant was constructed to disrupt the bridging CaM/NOS interaction, and its
      FMN-heme IET rate was decreased by 96 %. These results demonstrated a new role of
      the isoform-specific serine residue of the key CaM/FMN(NOS) bridging site in
      regulating the FMN-heme IET (possibly by tuning the alignment of the FMN and heme
      domains).

PMID- 22407543
TI  - MR-based thermometry of laser induced thermotherapy: temperature accuracy and
      temporal resolution in vitro at 0.2 and 1.5 T magnetic field strengths.
AB  - PURPOSE: To evaluate MR-thermometry using fast MR sequences for laser induced
      interstitial thermotherapy (LITT) at 0.2 and 1.5 T systems. METHODS & MATERIALS:
      In-vitro experiments were performed using Agarose gel mixture and lobes of
      porcine liver. MR-thermometry was performed by means of longitudinal relaxation
      time (T1) and proton resonance frequency shift (PRF) methods under acquisition of
      amplitude and phase shift images. Four different sequences were used for T1
      thermometry: A gradient-echo (GRE), a True Fast Imaging with Steady Precession
      (TRUFI), a Saturation Recovery Turbo-FLASH (SRTF), and an Inversion Recovery
      Turbo-FLASH (IRTF) sequence (FLASH-Fast Low Angle Shot). PRF was measured with
      four sequences: Two fast-spoiled GRE sequences (one as WIP sequence), a Turbo
      FLASH (TFL) sequence (WIP sequence), and a multiecho-TrueFISP sequence.
      Temperature was controlled and verified using a fiber-optic Luxtron device. The
      temperature was correlated with the MR measurement. RESULTS: All sequences showed
      a good linear correlation R(2) = 0.97-0.99 between the measured temperature and
      the MR-thermometry measurements. The only exception was the TRUFI sequence in the
      Agarose phantom that showed a non-linear calibration curve R(2) = 0.39-0.67. At
      1.5 T, the Agarose experiments revealed similar temperature accuracies of 4-6
      degrees C for all sequences excluding TRUFI. During experiments with the liver,
      the PRF sequences showed better performance than the T1, with accuracies of 5-12
      degrees C, contrary to the T1 sequences at 14-18 degrees C. The accuracy of the
      Siemens PRF-FLASH sequence was 5.1 degrees C. At 0.2 T, the Agarose experiments
      provided the highest accuracy of 3.3 degrees C for PRF measurement. At the liver
      experiments the T1 sequences SRTF and FLASH revealed the best accuracies at 6.4
      and 7.0 degrees C. CONCLUSION: The accuracy and speed of MR temperature
      measurements are sufficient for controlling the temperature-based tumor
      destruction. For 0.2 T systems SRTF and FLASH sequences are recommended. For 1.5
      T systems SRTF and FLASH are the most accurate.

PMID- 22407544
TI  - Filtered FCS: species auto- and cross-correlation functions highlight binding and
      dynamics in biomolecules.
AB  - An analysis method of lifetime, polarization and spectrally filtered fluorescence
      correlation spectroscopy, referred to as filtered FCS (fFCS), is introduced. It
      uses, but is not limited to, multiparameter fluorescence detection to
      differentiate between molecular species with respect to their fluorescence
      lifetime, polarization and spectral information. Like the recently introduced
      fluorescence lifetime correlation spectroscopy (FLCS) [Chem. Phys. Lett. 2002,
      353, 439-445], fFCS is based on pulsed laser excitation. However, it uses the
      species-specific polarization and spectrally resolved fluorescence decays to
      generate filters. We determined the most efficient method to generate global
      filters taking into account the anisotropy information. Thus, fFCS is able to
      distinguish species, even if they have very close or the same fluorescence
      lifetime, given differences in other fluorescence parameters. fFCS can be applied
      as a tool to compute species-specific auto- (SACF) and cross- correlation (SCCF)
      functions from a mixture of different species for accurate and quantitative
      analysis of their concentration, diffusion and kinetic properties. The computed
      correlation curves are also free from artifacts caused by unspecific background
      signal. We tested this methodology by simulating the extreme case of ligand
      receptor binding processes monitored only by differences in fluorescence
      anisotropy. Furthermore, we apply fFCS to an experimental single-molecule FRET
      study of an open-to-closed conformational transition of the protein Syntaxin-1.
      In conclusion, fFCS and the global analysis of the SACFs and SCCF is a key tool
      to investigate binding processes and conformational dynamics of biomolecules in a
      nanosecond-to-millisecond time range as well as to unravel the involved molecular
      states.

PMID- 22407545
TI  - Prior incarceration and barriers to receipt of services among entrants to
      alternative to incarceration programs: a gender-based disparity.
AB  - The high levels of health and psychosocial needs among correctional populations
      strongly shape the well-being of the urban communities from which a large number
      of criminal justice-involved individuals come or to which they return. The
      benefits of providing services to correction-involved individuals and linking
      them to providers such as with alternative to incarceration (ATI) programs may be
      limited if they encounter difficulties accessing such services. This study
      identified the types of barriers that have prevented entrants into ATI programs
      from receiving health and psychosocial services. We then tested the association
      between number of prior incarcerations and number of barriers by gender. From a
      random sample of adults (N = 322; 83 women and 239 men) entering ATI programs in
      New York City, data were collected via structured interviews that elicited self
      reported sociodemographics, substance use, prior incarcerations, and barriers
      that had actually prevented a participant from visiting or returning to a service
      provider. Participants reported an average of 3.0 barriers that have prevented
      them from receiving health and psychosocial services. The most prevalent barriers
      predominantly concerned service providers' inability to accommodate constraints
      on participants' time availability or flexibility, transportation, and money.
      Compared to women, men had a significantly different association that was in the
      adverse direction--i.e., more prior incarcerations was associated with more
      barriers--between prior incarcerations and encountering service barriers.
      Findings indicate that ATI program entrants experience many barriers that have
      prevented them from receiving health and/or psychosocial services. Furthermore,
      men with more extensive incarceration histories particularly are disadvantaged.
      ATI programs can improve the public health of urban communities if such programs
      are prepared and resourced to facilitate the receipt of services among program
      participants, especially men who have more extensive incarceration histories.

PMID- 22407546
TI  - Antiviral or proviral action of mycophenolic acid in hepatitis B infection?

PMID- 22407547
TI  - Nine genes that may contribute to partial trisomy (6)(p22->pter) and unique
      presentation of persistent hyperplastic primary vitreous with retinal detachment.
AB  - We report on a newborn girl with facial anomalies, a congenital heart defect,
      severe pre- and postnatal growth retardation, feeding problems, and persistent
      hyperplastic primary vitreous. Cytogenetic analysis by high resolution GTG
      banding showed extra chromosomal material on the short arm of one chromosome 1 of
      the patient, but neither parent. SKY and CGH analysis demonstrated that the
      patient had a de novo 46,XX, der(1)t(1;6)(p36.3; p22). Compared with previously
      reported cases of partial trisomy 6p22 syndrome, this patient exhibited a unique
      condition for this syndrome: persistent hyperplastic primary vitreous (PHPV) with
      retinal detachment. The human genome database was searched for candidate genes
      and we propose the following nine genes located in the 6p22->6pter region for
      their potential contribution to the phenotype of partial trisomy 6p22->pter and
      persistent hyperplastic primary vitreous (PHPV) with retinal detachment: Forkhead
      box Q1 (FOXQ1), FOXF2, FOXC1, NRN1, EDN1, ATXN1, DEK oncogene, E2F3, and NRNS1.

PMID- 22407548
TI  - Pyrolysis and mass spectrometry studies of meteoritic organic matter.
AB  - Meteorites are fragments of extraterrestrial materials that fall to the Earth's
      surface. The carbon-rich meteorites are derived from ancient asteroids that have
      remained relatively unprocessed since the formation of the Solar System 4.56
      billion years ago. They contain a variety of extraterrestrial organic molecules
      that are a record of chemical evolution in the early Solar System and subsequent
      aqueous and thermal processes on their parent bodies. The major organic component
      (>70%) is a macromolecular material that resists straightforward solvent
      extraction. In response to its intractable nature, the most common means of
      investigating this exotic material involves a combination of thermal
      decomposition (pyrolysis) and mass spectrometry. Recently the approach has also
      been used to explore controversial claims of organic matter in meteorites from
      Mars. This review summarizes the pyrolysis data obtained from meteorites and
      outlines key interpretations.

PMID- 22407549
TI  - A case of neurosyphilis presenting with myoclonus, cerebellar ataxia, and speech
      disturbance.

PMID- 22407550
TI  - Coexistence of a lung carcinosarcoma and hydatid cyst.

PMID- 22407551
TI  - The efficacy of medicinal leeches in plastic and reconstructive surgery: a
      systematic review of 277 reported clinical cases.
AB  - BACKGROUND: Although there are numerous case reports and small case series
      describing the experiences of leech therapy in various circumstances, there are
      relatively few large studies evaluating the effectiveness of leeching to relieve
      venous congestion. The therapeutic value of leeching is illustrated by these
      reports but the current literature lacks a cohesive summary of previous
      experiences. METHODS: An electronic search of PubMed, the Cochrane library and
      the Centre for Reviews and Dissemination between 1966 and 2009 was used to
      retrieve human studies published in the English language evaluating outcomes
      following leech therapy. The "success" and "failure" of leech therapy were the
      primary outcome measures and secondary outcomes included complications, number of
      leeches used, pharmacological adjuncts and blood transfusion requirements.
      RESULTS: In total, out of 461 articles, 394 articles met the exclusion criteria.
      The 67 included papers reported on 277 cases of leech use with an age range of 2
      81 years and a male to female ratio of almost 2:1. The overall reported "success"
      rate following leech therapy was 77.98% (216/277). In terms of secondary outcome
      measures, 49.75% of cases (N = 101) required blood transfusions, 79.05% received
      antibiotics (N = 166) and 54.29% received concomitant anticoagulant therapy. The
      overall complication rate was 21.8%. CONCLUSION: In the absence of robust
      randomized controlled trials on which the evidence may be based, this synthesis
      of current best evidence guides clinicians during the process of consenting
      patients and using leeches in their practice.

PMID- 22407552
TI  - Synthesis and characterization of 1,8-naphthalimide with [6]helicene skeleton.
AB  - A 1,8-naphthalimide with [6]helicene derivative scaffold has been designed and
      synthesized. The (P)- and (M)-enantiomers of the [6]helicene derivative were
      resolved by HPLC on a chiral column. The single crystal of the [6]helicene
      derivative exhibits an intermolecular interactions of the 1,8-naphthalimide
      units.

PMID- 22407553
TI  - Brief Multidimensional Students' Life Satisfaction Scale-PTPB Version (BMSLSS
      PTPB): psychometric properties and relationship with mental health symptom
      severity over time.
AB  - Youth life satisfaction is a component of subjective well-being, an important
      part of a strengths-based approach to treatment. This study establishes the
      psychometric properties of the Brief Multidimensional Students' Life Satisfaction
      Scale-PTPB Version (BMSLSS-PTPB). The BMSLSS-PTPB showed evidence of construct
      validity with significant correlations as expected to measures of youth hope and
      youth symptom severity, and no relationship as expected to youth treatment
      outcome expectations. A longitudinal analysis was conducted examining the
      relationship between youth-reported life satisfaction and mental health symptom
      severity (youth-, caregiver-, and clinician-report) for 334 youth (aged 11-18
      years) receiving in-home treatment. Results indicated that life satisfaction
      consistently increased over the course of treatment but increased faster in youth
      whose symptom severity, as rated by all reporters, decreased over the course of
      treatment. Implications, future directions, and limitations of the study are
      discussed.

PMID- 22407554
TI  - Satisfaction with Life Scale (SWLS) in caregivers of clinically-referred youth:
      psychometric properties and mediation analysis.
AB  - This paper presents the psychometric evaluation of the Satisfaction with Life
      Scale (SWLS; Diener et al. in J Personal Assess 49:71-75, 1985) used with a large
      sample (N = 610) of caregivers for youth receiving mental health services.
      Methods from classical test theory, factor analysis, and item response theory
      were utilized. Additionally, this paper investigated whether caregiver strain
      mediates the effect of youth symptom severity on caregiver life satisfaction (N =
      356). Bootstrapped confidence intervals were used to determine the significance
      of the mediated effects. Results indicated that the SWLS is a psychometrically
      sound instrument to be used with caregivers of clinically-referred youth.
      Mediation analyses found that the effect of youth symptom severity on caregiver
      life satisfaction was mediated by caregiver strain but that the mediation effect
      differed based on the type of youth symptoms: caregiver strain was a partial
      mediator when externalizing symptoms were measured and a full mediator when
      internalizing symptoms were measured. Implications for future research and
      clinical practice are discussed.

PMID- 22407555
TI  - The relationship between change in therapeutic alliance ratings and improvement
      in youth symptom severity: whose ratings matter the most?
AB  - This paper presents the psychometric evaluation of brief measures of therapeutic
      alliance (TA) for youths, clinicians and caregivers and a longitudinal analysis
      of relationships between changes in TA and changes in youth symptom and
      functioning severity. Psychometric analyses using methods from Classical Test
      Theory, Item Response Theory, and Factor Analysis indicate that the measures of
      TA used in this study offer something new for both practice and research. The
      measures have variability, sensitivity to change over time, brevity and can be
      used with multiple parties through parallel forms. The longitudinal analyses,
      employing hierarchical linear modeling with time-varying covariates, found that
      TA ratings of the clinician correlated with symptom improvement as rated by the
      clinician, caregiver and youth. Additional analyses showed that decreases in
      clinician-rated youth TA was most important in predicting a lower rate of youth
      improvement. Implications for future research and clinical practice are
      discussed.

PMID- 22407556
TI  - The symptoms and functioning severity scale (SFSS): psychometric evaluation and
      discrepancies among youth, caregiver, and clinician ratings over time.
AB  - This paper describes the development and psychometric evaluation of the symptoms
      and functioning severity scale (SFSS), which includes three parallel forms to
      systematically capture clinician, youth, and caregiver perspectives of youth
      symptoms on a frequent basis. While there is widespread consensus that different
      raters of youth psychopathology vary significantly in their assessment, this is
      the first paper that specifically investigated the discrepancies among clinician,
      youth, and caregiver ratings throughout the treatment process within a community
      mental health setting. Results for all three respondent versions indicated the
      SFSS is a psychometrically sound instrument for use in this population.
      Significant discrepancies in scores existed at baseline among the three
      respondents. Longitudinal analyses reveal the youth-clinician and caregiver
      clinician score discrepancies decreased significantly over time. Differences by
      youth gender existed for caregiver-clinician discrepancies. The average youth
      caregiver score discrepancy remained consistent throughout treatment.
      Implications for future research and clinical practice are discussed.

PMID- 22407557
TI  - Validation and use of the youth and caregiver Treatment Outcome Expectations
      Scale (TOES) to assess the relationships between expectations, pretreatment
      characteristics, and outcomes.
AB  - This study introduces the youth and caregiver versions of the Treatment Outcome
      Expectations Scale (TOES) and presents the results of comprehensive psychometric
      analyses in a large sample of clinically-referred youth (N = 291) ages 11-18 and
      their caregivers (N = 268). This study also examines whether expectations are
      predictive of early or overall treatment change as measured by changes in youth
      symptom severity rated by multiple respondents (youth, caregiver, and clinician).
      Additionally, the relationship between treatment outcome expectations and several
      background, pretreatment, and clinical variables is explored. Finally, this study
      investigates the correspondence in outcome expectations between dyads of youth
      and caregivers. Results demonstrate the TOES is a psychometrically sound measure
      for use in this population. Findings also indicate that while higher youth
      outcome expectations significantly relate to higher youth-rated internalizing
      symptom severity at baseline, they also relate to a faster rate of reduction in
      internalizing symptom severity. Additionally, caregiver age and youth gender were
      significant predictors of youth-rated outcome expectations. Results also
      demonstrate a small, positive correlation between youth and caregiver ratings of
      outcome expectations. Implications, future directions, and limitations of the
      study are discussed.

PMID- 22407558
TI  - Development and psychometric evaluation of the youth and caregiver Service
      Satisfaction Scale.
AB  - There is widespread need for the inclusion of service satisfaction measures in
      mental health services evaluation. The current paper introduces the Service
      Satisfaction Scale (SSS), a practical and freely available measure of global
      youth and adult caregiver service satisfaction. The development process, as well
      as results from a comprehensive psychometric evaluation in a large sample of
      clinically referred youth (N = 490) receiving home-based care, and their
      caregivers (N = 383), are presented. Multiple models for psychometric analyses
      were used including classical test theory, item response theory, and confirmatory
      factor analysis. As expected, SSS total scores were negatively skewed but the
      measure displayed otherwise adequate scale characteristics for both the youth and
      caregiver versions. Thus, the SSS is a brief and psychometrically sound
      instrument for measuring global satisfaction in home-based mental health service
      settings. It has several advantages compared to existing measures including
      brevity, parallel youth and caregiver forms, availability at no cost, and its
      development on a large sample of youth and caregivers with rigorous psychometric
      methodology.

PMID- 22407560
TI  - Why can't mental health services be more like modern baseball?

PMID- 22407559
TI  - Motivation for youth's treatment scale (MYTS): a new tool for measuring
      motivation among youths and their caregivers.
AB  - Treatment motivation can be important for treatment adherence and outcomes, yet
      few measures of motivation are available for youths in mental health settings.
      These authors describe the psychometric properties of the motivation for youth's
      treatment scale (MYTS), an 8-item measure with forms for youths and caregivers
      that assesses their problem recognition and treatment readiness. Results indicate
      that the MYTS offers practitioners and researchers a brief, psychometrically
      sound tool for assessing treatment motivation of youths and their caregivers.
      Multivariate analyses of clinical and non-clinical characteristics of youths and
      caregivers show that youths' symptom severity consistently predicts treatment
      motivation for both groups. However, the strain of caring for the youth adds
      significantly to caregivers' recognition of the youth's troubles. While caregiver
      and youth motivations correlate, their agreement is low. Caregivers are nearly
      always more treatment motivated than youths. The authors discuss the implications
      of their findings for measurement, treatment planning, and future research.

PMID- 22407561
TI  - Validation and use of the Children's Hope Scale-revised PTPB edition (CHS-PTPB):
      high initial youth hope and elevated baseline symptomatology predict poor
      treatment outcomes.
AB  - The present study examined the relationship between initial youth hope, measured
      within the first 4 weeks of mental health treatment, and treatment progress over
      time (self-, caregiver-, and clinician-report of symptom severity) in a clinical
      sample of youth ages 11-18 years (N = 356). The psychometric properties of the
      CHS-PTPB, a revised version of the Children's Hope Scale, are also presented.
      Results indicate the CHS-PTPB is a psychometrically sound measure for use in this
      population. Additionally, results found that while higher levels of hope were
      associated with lower levels of symptom severity at baseline, initial level of
      hope was not significantly related to symptom improvement over time as reported
      by the youth and caregiver. Surprisingly, higher initial hope predicted slower
      treatment progress as rated by clinicians. According to clinician-rated symptom
      severity, youth with high initial hope and high baseline symptom severity show
      the poorest predicted clinical outcome. Implications, future directions, and
      limitations of the study are discussed.

PMID- 22407562
TI  - Measurement Quality of the Caregiver Strain Questionnaire-Short Form 7 (CGSQ
      SF7).
AB  - This study examined the measurement quality of an abbreviated version of the
      Caregiver Strain Questionnaire. The CGSQ-Short Form 7 (CGSQ-SF7) is practical for
      routine assessment of objective and subjective internalized caregiver strain. The
      subjective externalized subscale is not included in the CGSQ-SF7. Findings
      indicate that the reliability and validity of the shortened objective and
      subjective internalized subscales are comparable to the original. Examination of
      construct validity suggested that caregiver, youth, and clinician ratings of
      child clinical severity were related to objective caregiver strain. However,
      youth and clinician ratings of child clinical severity were not related to
      subjective internalized caregiver strain.

PMID- 22407563
TI  - Measuring youths' perceptions of counseling impact: description, psychometric
      evaluation, and longitudinal examination of the Youth Counseling Impact Scale
      v.2.
AB  - The Youth Counseling Impact Scale (YCIS) is an empirically validated treatment
      progress measure that assesses youths' perceptions of the short term
      effectiveness of therapy. Since its initial publication, the original 10-item
      measure has been shortened to ease measurement burden and revised to include a
      question about a youth's insight into his or her strengths. The current study
      describes the development of the revised YCIS (v.2) and evaluates its
      psychometric properties. Additionally, this study examines whether the YCIS (v.2)
      total score or subscale scores change over time and investigates whether there
      are gender or age differences for youths' perceptions of the impact of therapy.
      Results found the revised version obtained comparable information to that of the
      original measure, and that the revised version retained the factor structure of
      the original model with one primary general factor of Counseling Impact and two
      secondary factors (Insight and Change). Results also suggested that while the
      YCIS (v.2) total score and Change subscale score did not change linearly over the
      course of treatment, the Insight subscale score showed a small but significant
      linear increase over time. No significant differences in YCIS scores based on
      youth age or gender were found. The implication of these findings, the clinical
      and empirical utility of this measure, and its limitations are discussed.

PMID- 22407564
TI  - The Session Report Form (SRF): are clinicians addressing concerns reported by
      youth and caregivers?
AB  - This study explores the relationship between clinician-reported content addressed
      in sessions, measured with the Session Report Form (SRF), and multi-informant
      problem alerts stemming from a larger battery of treatment process and progress
      measures. Multilevel Multinomial Logit Models were conducted with 133 clinicians
      and 299 youths receiving home-based treatment (N = 3,143 sessions). Results
      indicate a strong relationship between session content and problems related to
      youth symptoms and functioning as reported by clinicians in the same session.
      Session content was related to emotional, family, and friend/peer problems
      reported by youth and youth behavioral problems reported by caregivers. High-risk
      problems (alcohol/substance use, harm to self or others) were strongly related to
      session content regardless of informant. Session content was not related to
      problem alerts associated with the treatment process, caregiver strain, or
      client/caregiver strengths. The SRF appears to be a useful measure for assessing
      common themes addressed in routine mental health settings.

PMID- 22407565
TI  - Secondary metabolites from the phloem of Piper solmsianum (Piperaceae) in the
      honeydew of Edessa meditabunda.
AB  - INTRODUCTION: The phytochemistry of species of the genus Piper has been studied
      extensively, including Piper solmsianum. However, no studies have addressed the
      phytochemistry of the sap content of Piper species. OBJECTIVE: To evaluate the
      transferring of secondary compounds from the saps of P. solmsianum to the
      honeydew of Edessa meditabunda. METHODOLOGY: The honeydew of E. meditabunda and
      saps of P. solmsianum were analysed by GC-MS, (1) H-NMR and LC-MS. RESULTS: The
      lignan (-)-grandisin and the phenylpropanoid (E)-isoelemicin were detected in
      both saps of P. solmsianum and honeydew of E. meditabunda. CONCLUSION: Analysis
      of honeydew secreted by the sap-sucking insect E. meditabunda indicated that (-)
      grandisin and (E)-isoelemicin are absorbed from the phloem of Piper solmsianum.

PMID- 22407566
TI  - Synthesis of heterobifunctional protein fusions using copper-free click chemistry
      and the aldehyde tag.

PMID- 22407567
TI  - AP-PCR detection of Streptococcus mutans and Streptococcus sobrinus in caries
      free and caries-active subjects.
AB  - The aim of the study was to identify the number and distribution of genotypes of
      Streptococcus mutans (S. mutans) and Streptococcus sobrinus (S. sobrinus)
      isolated from caries-free and caries-active subjects. Non-stimulated saliva,
      buccal smooth surface of the right upper teeth, fissures of sound occlusal
      surface, and carious surface were sampled from 7 caries-free and 7 caries-active
      (DMFT >= 6) students aged 22-24 years. S. mutans and S. sobrinus were isolated
      using Chelex-100 and primarily identified by colony morphology and biochemical
      characteristics. The isolates of S. mutans were genotyped using arbitrarily
      primed polymerase chain reaction. A total of 516 isolates of S. mutans were
      genotyped from 47 sites in 14 students, and 44 different genotypes were
      determined. All of the caries-free individuals harbored S. mutans but not S.
      sobrinus, although individuals 3 and 7 had no S. mutans in their saliva. The CFU
      value of S. mutans on carious surfaces was the highest, and values in saliva,
      fissures, and occlusal surfaces were higher in caries-active individuals than in
      caries-free individuals. We detected 28 genotypes of S. mutans in caries-free
      individuals, each of who carried more than 3 genotypes. However, we found only 16
      genotypes of S. mutans in caries-active individuals, each of who carried no more
      than 3 genotypes. More genotypes are harbored in the saliva, fissures, and smooth
      surfaces of caries-free individuals than of caries-active individuals. The
      proportion of samples positive for S. mutans and S. sobrinus was significantly
      higher in caries-active individuals than in caries-free individuals, and the
      presence of these species is a risk factor for high DMFT in dental caries.
      Isolates of S. mutans exist that have apparent genetic diversity. The genotypes
      of isolates might relate to differences in caries susceptibility.

PMID- 22407568
TI  - Molecular cloning and expression analysis of tyrosinase gene in the skin of
      Jining Gray Goat (Capra hircus).
AB  - Tyrosinase is the key regulatory enzyme of melanogenesis and plays a major role
      in mammal coat color. For the first time, we have sequenced and characterized the
      tyrosinase (TYR) of Jining Gray Goat (Capra hircus), which is the world-famous
      fur-bearing animal with its special color and pattern. The full-length cDNA was
      cloned by a reverse-transcription polymerase chain reaction (RT-PCR) and rapid
      amplification of cDNA end (RACE) method. As a result, one 2131-bp nucleotide
      sequence representing the full-length cDNA of TYR was obtained. The entire open
      reading frame (ORF) of the TYR is 1593 bp and encodes for 530 amino acids, which
      is well conserved compared with TYR of various species with higher degree of
      sequence similarity with other mammalian (74-99 %) than amphibian, aves, and
      fishes (56-73 %). The deduced amino acids contained one signal peptide, one
      transmembrane domain, five N-linked glycosylation sites, and two copper binding
      sites. The result of real-time quantitative PCR showed that the expression level
      of TYR was the highest in the dark-gray goats and the lowest in the light-gray
      ones, while the goats of dark-gray individuals have more than 50 % black fiber
      and light-gray ones less than 30 %. During the whole life of Jining gray goat,
      TYR expression level changes with certain regularity and their coat color will
      change correspondingly by investigating the expression level in ten development
      stages. After comparing the result and the coat phenotype, we presume that it
      seems to have a positive relationship between the color depth of coat and the
      expression level of TYR.

PMID- 22407570
TI  - Ruthenium(II)-polyimine-coumarin light-harvesting molecular arrays: design
      rationale and application for triplet-triplet-annihilation-based upconversion.
AB  - Ru(II)-bis-pyridine complexes typically absorb below 450 nm in the UV spectrum
      and their molar extinction coefficients are only moderate (epsilon<16,000  M(-1) 
      cm(-1)). Thus, Ru(II)-polyimine complexes that show intense visible-light
      absorptions are of great interest. However, no effective light-harvesting
      ruthenium(II)/organic chromophore arrays have been reported. Herein, we report
      the first visible-light-harvesting Ru(II)-coumarin arrays, which absorb at 475 nm
      (epsilon up to 63,300  M(-1)  cm(-1), 4-fold higher than typical Ru(II)-polyimine
      complexes). The donor excited state in these arrays is efficiently converted into
      an acceptor excited state (i.e., efficient energy-transfer) without losses in the
      phosphorescence quantum yield of the acceptor. Based on steady-state and time
      resolved spectroscopy and DFT calculations, we proposed a general rule for the
      design of Ru(II)-polypyridine-chromophore light-harvesting arrays, which states
      that the (1)IL energy level of the ligand must be close to the respective energy
      level of the metal-to-ligand charge-transfer (MLCT) states. Lower energy levels
      of (1)IL/(3)IL than the corresponding (1)MLCT/(3)MLCT states frustrate the
      cascade energy-transfer process and, as a result, the harvested light energy
      cannot be efficiently transferred to the acceptor. We have also demonstrated that
      the light-harvesting effect can be used to improve the upconversion quantum yield
      to 15.2 % (with 9,10-diphenylanthracene as a triplet-acceptor/annihilator),
      compared to the parent complex without the coumarin subunit, which showed an
      upconversion quantum yield of only 0.95 %.

PMID- 22407569
TI  - Characterization of the cytokine expression profiles of the aorta and liver of
      young tumor necrosis factor alpha mutant mice.
AB  - Both the aorta and the liver are major organs that play important roles in lipid
      metabolism, and they are subject to systemic as well as local inflammatory
      responses in metabolic syndrome. Our previous study indicated that TNFalpha
      deficiency influences atherogenesis by reducing inflammation of the aorta. To
      better understand this phenomenon, the mRNA and protein expression profiles of a
      panel of cytokines in the aorta and liver of young TNFalpha-null (TNFalpha(-/-))
      mice were analyzed and compared with age- and gender-matched wild-type (WT)
      control mice. In the aorta, IL-2 and GM-CSF were up-regulated versus WT mice,
      while IL-1beta, IL-4, IL-6, IL-10, MCP-1, IFN-gamma, and the adhesion molecules
      ICAM-1 and VCAM-1 were down-regulated. In the liver, however, the expressions of
      NF-kappaB, IL-1, IL-2, IL-6, IL-10, ICAM-1, and VCAM-1 were significantly up
      regulated in TNFalpha(-/-) mice, while IFN-gamma and IL-4 were down-regulated.
      Out of the 62 cytokines analyzed, 22 in the aorta and 27 in the liver were
      altered by 2-fivefolds at the protein level in TNFalpha(-/-) mice. Our data
      demonstrated that the loss of TNFalpha function led to various changes in the
      levels of cytokine expression in these organs at both the transcriptional and
      translational levels. These results indicated that the changes in cytokine
      expression patterns in the aorta and the liver may further influence the
      progression of systemic or local lipid metabolism dysregulation and pathogenesis
      in animals with TNFalpha dysfunction representing inflammation-related diseases,
      such as atherosclerosis and metabolic syndrome.

PMID- 22407571
TI  - Iron deposition in multiple sclerosis lesions measured by susceptibility-weighted
      imaging filtered phase: a case control study.
AB  - PURPOSE: To investigate phase lesions identified on susceptibility-weighted
      imaging (SWI)-filtered phase images in patients with multiple sclerosis (MS),
      clinically isolated syndrome (CIS) and healthy controls (HC). To relate phase
      lesion characteristics to other clinical and MRI outcomes. MATERIALS AND METHODS:
      95 relapsing-remitting (RR), 40 secondary-progressive (SP) MS patients, as well
      as 19 CIS patients and 49 age- and sex-matched HC, were scanned on a 3T scanner.
      Phase-, T1-, and T2-lesion characteristics were determined. Overlap of T1- and T2
      weighted imaging (WI) lesions with phase lesions (T1P and T2P), as well as brain
      atrophy outcomes, was assessed. RESULTS: MS patients showed significantly greater
      numbers and larger volume of phase lesions, compared with HC (P < 0.001). 23.6%
      of T2 lesions overlapped with phase lesions, whereas the same figure for T1
      lesions was 37.3%. Conversely, 33.4% and 69.7% of phase lesions were not visible
      on T2- or T1-WI, respectively. Phase, T1P and T2P lesions were not related to
      clinical outcomes, but phase lesions were related to ventricular enlargement.
      CONCLUSION: Phase lesions were present in both MS and CIS patients, and showed
      partial overlap with lesions observed using conventional MRI. The role of phase
      lesions in clinical progression remains unclear and should be further explored.

PMID- 22407572
TI  - Parallel factor analysis of ovarian autofluorescence as a cancer diagnostic.
AB  - BACKGROUND AND OBJECTIVES: Endogenous fluorescence from certain amino acids,
      structural proteins, and enzymatic co-factors in tissue is altered by
      carcinogenesis. We evaluate the potential of these changes in fluorescence to
      predict a diagnosis of malignancy and to estimate the risk of developing ovarian
      cancer. STUDY DESIGN/MATERIALS AND METHODS: Ovarian biopsies were interrogated
      over 270-550 nm excitation and fluorescence was collected from 290 to 700 nm. Two
      hundred forty-nine measurements were performed on 49 IRB-consented patients
      undergoing oophorectomy. Data are analyzed using parallel factor analysis to
      determine excitation and emission spectra of the underlying fluorophores that
      contribute to the total detected fluorescence intensity. RESULTS: Using
      multivariate normal distribution fits and cross-validation techniques,
      sensitivity and specificity of 88% and 93%, respectively, are achieved when
      classifying malignant samples versus others, while 88% and 80%, respectively, are
      achieved when classifying normal post-menopausal patients as being either at high
      or low-risk of developing ovarian cancer based on their personal and family
      history of cancer. Performance of classifying cancer increases when the normal
      group does not include benign neoplasm and endometriosis samples. Performance of
      high- versus low-risk classification decreases when normal samples include both
      pre- and post-menopausal women. Excitation over 270-400 and 380-560 nm,
      respectively, have the best diagnostic performance for cancer detection and risk
      status assessment. CONCLUSIONS: Assessing the endogenous fluorescence could be
      useful in screening women at increased risk of developing ovarian cancer.

PMID- 22407573
TI  - Local Structure of ZnO micro flowers and nanoparticles obtained by micro
      segmented flow synthesis.
AB  - The micro-segmented flow technique was applied for continuous synthesis of ZnO
      micro- and nanoparticles with short residence times of 9.4 s and 21.4 s,
      respectively. The obtained particles were characterized by scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM). Small angle X-ray
      scattering (SAXS) and photoluminescence spectroscopy were used to determine the
      size and optical properties of ZnO nanoparticles. In addition, extended X-ray
      absorption fine structure (EXAFS) spectroscopy was employed to investigate local
      structural properties. The EXAFS measurements reveal a larger degree of
      structural disorder in the nanoparticles than the microparticles. These
      structural changes should be taken into consideration while evaluating the size
      dependent visible emission of ZnO nanoparticles.

PMID- 22407574
TI  - Severe drug eruptions revisited.
AB  - Genetic and non-genetic factors can alter the action of a medicinal drug,
      resulting in a wide range of responses in different individuals. Among the many
      potential side effects of therapies, a drug eruption is an adverse drug reaction
      in the skin. Genetic associations between HLA haplotype and drug eruption have
      been reported, and immune responses against latent herpesvirus have also been
      implicated in some forms of this syndrome. We believe that it is essential to
      understand the immune mechanisms by which some drugs induce hypersensitivity so
      that we can better target these pathways to limit drug side effects. The
      identification of patient risk factors for drug eruptions will allow the rational
      design of novel immunotherapies for these life-threatening reactions, and the
      development of alternative interventions for high-risk patients.

PMID- 22407575
TI  - Resistance to TRAIL and how to surmount it.
AB  - Development of resistance to TRAIL-induced toxicity is one of the strategies used
      from tumor cells to escape destruction from the immune system. This process may
      occur through aberrant expression of functional receptors, overexpression of
      decoy receptors on tumor cell membrane, or malfunctioning of downstream signals
      triggered by specific ligation of TRAIL. Numerous cytostatic, but also
      noncytostatic, drugs like protease inhibitors and NO-hybridized molecules have
      been shown to revert sensitivity of neoplastic cells to TRAIL by means of
      different mechanisms. This paper will review the possible routes of
      reconstitution of sensitivity to TRAIL-mediated immune response by specific
      modulation of different signals responsible for the development of resistance at
      both the membrane and the intracellular levels. Moreover, we will review and
      suggest novel strategies, aimed at resetting immune cell efficiency in cancer
      treatment.

PMID- 22407576
TI  - Immune predictors of cancer progression.
AB  - The immune system has multiple, complex, and sometimes opposing roles during
      cancer progression. While immune-compromised individuals have a higher incidence
      of cancers, inflammation is also associated with increased risk of disease
      progression. It is becoming apparent that simple measures of immune responses in
      the blood are of limited use in cancer. Instead, the importance of the exact
      identity and functional characteristics of tumor-infiltrating immune cells is
      increasingly recognized. This realization has led to recent studies that have
      revealed a critical role for chemokine expression in the tumor microenvironment
      and suggested a therapeutic potential of manipulating intratumoral expression of
      chemokines to alter the local immune milieu.

PMID- 22407577
TI  - Peeking into the secret life of neutrophils.
AB  - The migration of neutrophils between tissue compartments is an important aspect
      of innate immune surveillance. This process is regulated by a cascade of cellular
      and molecular signals to avoid unnecessary crowding of neutrophils at the
      periphery, to allow rapid mobilization of neutrophils in response to inflammatory
      stimuli, and to return to a state of homeostasis after the response. Intravital
      microscopy approaches have been fundamental in unraveling many aspects of
      neutrophil behavior, providing important mechanistic information on the processes
      involved in basal and disease states. Here, we provide a broad overview of the
      current state of research on neutrophil biology, describing the processes in the
      typical life cycle of neutrophils, from their first appearance in the bone marrow
      until their eventual destruction. We will focus on novel aspects of neutrophil
      behavior, which had previously been elusive until their recent elucidation by
      advanced intravital microscopy techniques.

PMID- 22407579
TI  - Assessing autistic traits in a Taiwan preschool population: cross-cultural
      validation of the Social Responsiveness Scale (SRS).
AB  - The cross-cultural validity of the Mandarin-adaptation of the social
      responsiveness scale (SRS) was examined in a sample of N = 307 participants in
      Taiwan, 140 typically developing and 167 with clinically-diagnosed developmental
      disorders. This scale is an autism assessment tool that provides a quantitative
      rather than categorical measure of social impairment in the general population.
      SRS total and subscale scores distinguished significantly between autism spectrum
      disorder and other developmental disorders (p < 0.01). Total SRS scores and
      sensitivity and specificity of the scale for diagnosing developmental disorders
      in the Taiwan study were similar to those observed in Western studies. These
      findings support the cross-cultural validity of the SRS scale for detecting
      autistic traits and for distinguishing between autism and other neuropsychiatric
      conditions.

PMID- 22407578
TI  - Disrupted stimulus control but not reward sensitivity in individuals with autism
      spectrum disorders: a matching law analysis.
AB  - The matching law suggests that behavior is emitted in proportion to the level of
      reinforcement available. The current study investigated this effect in
      individuals with autism spectrum disorders (ASD), and focused on the effects of
      magnitude of reinforcement (Study 1), and rate of reinforcement (Studies 2 and
      3), on matching performance. Studies 1 and 2 employed lower functioning children
      with ASD, and demonstrated matching in both groups, but that the group with ASD
      displayed greater levels of stimulus bias. Study 3 employed higher functioning
      children with ASD, and found little evidence of matching, but higher stimulus
      bias in the group with ASD. These effects suggest a disruption of stimulus
      control, but not reward sensitivity, in individuals with ASD.

PMID- 22407581
TI  - Influence of a 3-month training program on muscular damage and neutrophil
      function in male university freshman judoists.
AB  - We studied the effects of a high intensity and high frequency 3-month training
      program on muscle damage and neutrophil function in male judoists. The study
      included 15 male judoists who started intensive judo training program after a 6
      month break. Creatine kinase (CK), neutrophil counts and reactive oxygen species
      (ROS) production capability as well as phagocytic activity (PA) of neutrophils
      were measured at 2 stages; entering university (pre-training) and after 3-month
      training (post-training). At both points, we investigated parameters three times:
      just before, immediately after and 24 h after a 2-h practice session. Practice
      mediated change in CK was lower at post-training than at pre-training. Neutrophil
      count significantly increased after 2-h practice but recovered 24 h later whereas
      it showed no subsequent and further increased at 24 h post-practice. Although
      neutrophil ROS production capability and PA both decreased (breakdown) after
      practice session, ROS production capability increased and PA decreased (well
      adapted) at the post-training. Long-term training strengthened muscular function
      and improved neutrophil reaction against practice-mediated stress.

PMID- 22407580
TI  - Eyewitness testimony in autism spectrum disorder: a review.
AB  - Autism spectrum disorder (ASD) is estimated to affect around 1% of the
      population, and is characterised by impairments in social interaction,
      communication, and behavioural flexibility. A number of risk factors indicate
      that individuals with ASD may become victims or witnesses of crimes. In addition
      to their social and communication deficits, people with ASD also have very
      specific memory problems, which impacts on their abilities to recall eyewitnessed
      events. We begin this review with an overview of the memory difficulties that are
      experienced by individuals with ASD, before discussing the studies that have
      specifically examined eyewitness testimony in this group and the implications for
      investigative practice. Finally, we outline related areas that would be
      particularly fruitful for future research to explore. 

PMID- 22407582
TI  - A 4,5-diphosphino-substituted imidazolium salt: a building block for the modular
      synthesis of mixed diphosphine-NHC heterometallic complexes.
AB  - Fused in the same molecule! An N-heterocyclic carbene and a diphosphine are
      generated and used in the modular synthesis of a variety of target heterometallic
      complexes. The experimental approach involves formation of a unique 4,5
      bis(diphenylphosphino)-1,3-dimethyl-imidazolium salt, simply by starting from 1
      methylimidazole (see scheme; M(1) = Cr, Mn; M(2) = Au, Rh, Pd; LiHMDS =
      LiN(SiMe(3))(2)).

PMID- 22407583
TI  - Rounding up the usual suspects.

PMID- 22407584
TI  - The art in dermatitis.

PMID- 22407586
TI  - Morphological, molecular and cross-breeding analysis of geographic populations of
      coconut-mite associated predatory mites identified as Neoseiulus baraki: evidence
      for cryptic species?
AB  - Surveys were conducted in Brazil, Benin and Tanzania to collect predatory mites
      as candidates for control of the coconut mite Aceria guerreronis Keifer, a
      serious pest of coconut fruits. At all locations surveyed, one of the most
      dominant predators on infested coconut fruits was identified as Neoseiulus baraki
      Athias-Henriot, based on morphological similarity with regard to taxonomically
      relevant characters. However, scrutiny of our own and published descriptions
      suggests that consistent morphological differences may exist between the Benin
      population and those from the other geographic origins. In this study, we
      combined three methods to assess whether these populations belong to one species
      or a few distinct, yet closely related species. First, multivariate analysis of
      32 morphological characters showed that the Benin population differed from the
      other three populations. Second, DNA sequence analysis based on the mitochondrial
      cytochrome oxidase subunit I (COI) showed the same difference between these
      populations. Third, cross-breeding between populations was unsuccessful in all
      combinations. These data provide evidence for the existence of cryptic species.
      Subsequent morphological research showed that the Benin population can be
      distinguished from the others by a new character (not included in the
      multivariate analysis), viz. the number of teeth on the fixed digit of the female
      chelicera.

PMID- 22407585
TI  - Changing clinical practice through patient specific reminders available at the
      time of the clinical encounter: systematic review and meta-analysis.
AB  - OBJECTIVE: To synthesise current evidence for the influence on clinical behaviour
      of patient-specific electronically generated reminders available at the time of
      the clinical encounter. DATA SOURCES: PubMed, Cochrane library of systematic
      reviews; Science Citation Index Expanded; Social Sciences Citation Index; ASSIA;
      EMBASE; CINAHL; DARE; HMIC were searched for relevant articles. STUDY ELIGIBILITY
      CRITERIA, PARTICIPANTS AND INTERVENTIONS: We included controlled trials of
      reminder interventions if the intervention was: directed at clinician behaviour;
      available during the clinical encounter; computer generated (including computer
      generated paper-based reminders); and generated by patient-specific (rather than
      condition specific or drug specific) data. STUDY APPRAISAL AND SYNTHESIS METHODS:
      Systematic review and meta-analysis of controlled trials published since 1970. A
      random effects model was used to derive a pooled odds ratio for adherence to
      recommended care or achievement of target outcome. Subgroups were examined based
      on area of care and study design. Odds ratios were derived for each sub-group. We
      examined the designs, settings and other features of reminders looking for
      factors associated with a consistent effect. RESULTS: Altogether, 42 papers met
      the inclusion criteria. The studies were of variable quality and some were
      affected by unit of analysis errors due to a failure to account for clustering.
      An overall odds ratio of 1.79 [95% confidence interval 1.56, 2.05] in favour of
      reminders was derived. Heterogeneity was high and factors predicting effect size
      were difficult to identify. LIMITATIONS: Methodological diversity added to
      statistical heterogeneity as an obstacle to meta-analysis. The quality of
      included studies was variable and in some reports procedural details were
      lacking. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The analysis suggests a
      moderate effect of electronically generated, individually tailored reminders on
      clinician behaviour during the clinical encounter. Future research should
      concentrate on identifying the features of reminder interventions most likely to
      result in the target behaviour.

PMID- 22407587
TI  - Phenazepam abuse in the UK: an emerging problem causing serious adverse health
      problems, including death.
AB  - OBJECTIVE: Phenazepam (fenazepam; 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4
      benzodiazepin-2-one; PNZ, 'Bonsai') is a benzodiazepine developed in the former
      Soviet Union during the 1970s to treat neurological disorders, epilepsy, and
      alcohol withdrawal syndrome. Its recreational use appears to have increased over
      recent years. Because of the lack of accessible data on this substance, it is
      important that information is made available to health professionals. METHODS: A
      literature search was conducted in relevant databases (Medline, Toxbase,
      PsychInfo, etc.), grey literature (using Google Scholar) and Internet sites to
      identify key data on phenazepam, including epidemiology such as availability,
      price, supply sources, confiscations, and health-related problems. RESULTS:
      Information from these sources indicates the potential for serious adverse health
      consequences for this drug when taken recreationally and that its use is
      spreading in the USA and Europe. Although first use was reported in the UK in
      October 2009, major concerns in the UK arose in summer 2010 when individuals
      across Britain were admitted to hospital following overdose. Nine UK fatalities
      were reported in which phenazepam was detected in post mortem toxicology but not
      implicated in death. The first UK death directly involving phenazepam was
      notified in July and the second in November 2011. CONCLUSIONS: This paper
      summarises the key information about phenazepam abuse and health problems of
      which health professionals, especially those in Emergency Departments, should be
      aware and presents new information in respect of fatalities caused by the drug.

PMID- 22407588
TI  - Gas-phase dissociation of glycosylated peptide ions.
AB  - Among the myriad of protein post-translational modifications (PTMs),
      glycosylation presents a singular analytical challenge. On account of the
      extraordinary diversity of protein-linked carbohydrates and the great complexity
      with which they decorate glycoproteins, the rigorous establishment of glycan
      protein connectivity is often an arduous experimental venture. Consequently,
      elaborating the interplay between structures of oligosaccharides and functions of
      proteins they modify is usually not a straightforward task. A more mature
      biochemical appreciation of carbohydrates as PTMs will significantly hinge upon
      analytical advances in the field of glycoproteomics. Undoubtedly, the analysis of
      glycosylated peptides by tandem mass spectrometry (MS/MS) will play a pivotal
      role in this regard. The goal of this review is to summarize, from an analytical
      and tutorial perspective, the present state of knowledge regarding the
      dissociation of glycopeptide ions as accomplished by various MS/MS methods. In
      addition, this review will endeavor to harmonize some seemingly disparate
      findings to provide a more complete and broadly applicable description of
      glycopeptide ion fragmentation. A fuller understanding of the rich variety of
      glycopeptide dissociation behaviors will allow glycoproteomic researchers to
      maximize the information yielded by MS/MS experiments, while also paving the way
      to new innovations in MS-based glycoproteomics.

PMID- 22407590
TI  - The effects of H-bonding and sterics on the photoreactivity of a trimethyl
      butyrophenone derivative.
AB  - The irradiation of ester 1 in methanol and chloroform does not yield any
      photoproducts, whereas the photolysis of 1 in dry argon-saturated benzene
      produces cyclobutanol 4, which is converted to lactone 5 by the addition of HCl.
      Laser-flash photolysis of ester 1 demonstrates that 1 undergoes intramolecular H
      atom abstraction to form the biradical 2 (lambda(max)~ 310 nm, tau = 200 ns,
      benzene), which intersystem crosses to photoenols, Z-3 (lambda(max)~ 380 nm, tau
      = 30-60 MUs, benzene) and E-3 (lambda(max)~ 380 nm, tau = 11 ms, benzene).
      Density functional theory calculations were performed to support the proposed
      mechanism for forming cyclobutanol 4 and to explain how steric demand facilitates
      photoenol E-3 to form cyclobutanol 4 rather than lactone 5.

PMID- 22407589
TI  - Clinical description of a patient carrying the smallest reported deletion
      involving 10p14 region.
AB  - Haploinsufficiency of a region located distal to 10p14 designated HDR1, is
      responsible for hypoparathyroidism, sensorineural deafness, and renal anomalies
      (HDR syndrome). Haploinsufficiency of a more proximal region, located on 10p13
      10p14, designated as DGCR2 is associated with congenital heart defects and thymus
      hypoplasia/aplasia or T cell defect. We describe a patient showing facial
      dysmorphisms, delayed psychomotor development and bilateral sensorineural hearing
      loss and carrying a 10p14 deletion, the smallest deletion found in the literature
      so far. Our patient, carrying a partial deletion of the DGCR2 region and of the
      HDR1 region, including the GATA3 gene, showed, unexpectedly, only few of the
      clinical features of DiGeorge 2 syndrome (psychomotor retardation, palpebral
      ptosis, epicanthic folds, anteverted nares, cryptorchidism, hand/foot
      abnormalities) and did not show other typical signs, such as cardiac defect,
      cleft palate, and abnormal T cell levels. Of the three characteristic features of
      the HDR syndrome, our patient had only sensorineural deafness. On the basis of
      the revision of the other cases reported in the literature with a deletion
      including the 10p14 region, we suggest that GATA3 haploinsufficiency, although
      not recorded for each patient, is responsible for deafness. The present case
      shows that even this small 10p deletion is responsible for a specific phenotype.
      We also underline the importance of CGH-array, in order to obtain a more precise
      physical mapping of the 10p deletions and an accurate genotype-phenotype
      correlation.

PMID- 22407591
TI  - Atypical venous glomangioma causing chronic compression of the radial sensory
      nerve in the forearm. A case report and review of the literature.
AB  - Extrinsic chronic nerve compression induced by nonendothelium derived vascular
      tumors is a rare occurrence at the forearm level. We present a case of severe
      chronic compression of the radial sensory nerve (RSN) caused by an undiagnosed
      venous glomangioma. The tumor was excised with complete symptoms relief. In the
      presence of severe nerve compression syndromes in young age, without predisposing
      comorbidities, atypical extrinsic compression due to vascular tumors should be
      considered.

PMID- 22407592
TI  - Lesson learned from early and long-term results of 327 cases of coexisting
      surgical abdominal diseases and aortic aneurysms treated in open and endovascular
      surgery.
AB  - Patients with abdominal aortic aneurysm (AAA) frequently have other abdominal
      pathologies of surgical interest (other diseases, OD). Out of 1,375 elective open
      aortic replacements for AAA, 315 cases with OD were subdivided in Group 1 (82
      patients with "clean wound" OD) and Group 2 (233 patients with "clean
      contaminated wound" OD). The results of the sub-groups in which OD was treated at
      the same time as AAA were analysed (1a, 66 cases and 2a, 86 cases) and compared
      with OD not treated at the same time as AAA (1b, 16 cases and 2b, 147 cases).
      EVAR was done in 12 patients with a infrarenal AAA and concomitant abdominal
      disease. In this group post-operative complications occurred in two patients
      (endoleaks) and no sign of endograft infection was developed. Mean follow-up was
      36 months. Mortality was 0% in Group 1a, 1b, 2b and 5.8% in Group 2a. In Group 1a
      there were one haemoperitoneum, one ischaemic colitis and one graft infection. In
      Group 1b there were 4 nefrectomies for renal carcinoma and three emergency hernia
      repairs within 18 months from AAA operation. In Group 2a the follow-up was
      uneventful. In Group 2b there was no acute complication of OD and 57.2% of
      patients were subsequently operated for OD. In the EVAR group the 30-day and late
      mortality rates were 0 and 25%, respectively and all deaths were cancer-related.
      Contemporary correction of OD in open surgery for AAA should be performed in
      clean wound cases, while clean-contaminated operations can be done only in
      selected cases. EVAR is a valid alternative technique to open vascular surgery
      for the concomitant treatment of aortic aneurysms and abdominal pathologies.

PMID- 22407593
TI  - A case of extensive genitourinary tuberculosis: combined augmentation ileo
      cystoplasty, ureteric ileal replacement and buccal mucosal graft urethroplasty.
AB  - Genitourinary tuberculosis (GUTB) is the second most common form of
      extrapulmonary TB after lymph nodes. Advanced GUTB leading to strictures of
      ureters and urethra, and bladder contracture frequently need surgical management.
      These are usually treated by ileal replacement of ureter, substitution
      urethroplasty using buccal mucosal graft (BMG) and augmentation ileo-cystoplasty,
      respectively. These procedures have been well demonstrated individually but all
      these three procedures have never been combined as single procedure in the same
      patient. We report a case of advanced GUTB with ureteric and urethral strictures,
      and bladder contracture which was treated by the ileal replacement of ureter,
      augmentation ileo-cystoplasty combined with BMG substitution urethroplasty in a
      single sitting.

PMID- 22407594
TI  - A glycosyltransferase inhibitor from a molecular fragment library simultaneously
      interferes with metal ion and substrate binding.

PMID- 22407595
TI  - S-adenosyl methionine regulates ubiquitin-conjugating enzyme 9 protein expression
      and sumoylation in murine liver and human cancers.
AB  - Ubiquitin-conjugating enzyme 9 (Ubc9) is required for sumoylation and is
      overexpressed in several malignancies, but its expression in hepatocellular
      carcinoma (HCC) is unknown. Hepatic S-adenosyl methionine (SAMe) levels decrease
      in methionine adenosyltransferase 1A (Mat1a) knockout (KO) mice, which develop
      HCC, and in ethanol-fed mice. We examined the regulation of Ubc9 by SAMe in
      murine liver and human HCC, breast, and colon carcinoma cell lines and specimens.
      Real-time polymerase chain reaction and western blotting measured gene and
      protein expression, respectively. Immunoprecipitation followed by western
      blotting examined protein-protein interactions. Ubc9 expression increased in HCC
      and when hepatic SAMe levels decreased. SAMe treatment in Mat1a KO mice reduced
      Ubc9 protein, but not messenger RNA (mRNA) levels, and lowered sumoylation.
      Similarly, treatment of liver cancer cell lines HepG2 and Huh7, colon cancer cell
      line RKO, and breast cancer cell line MCF-7 with SAMe or its metabolite 5'
      methylthioadenosine (MTA) reduced only Ubc9 protein level. Ubc9 posttranslational
      regulation is unknown. Ubc9 sequence predicted a possible phosphorylation site by
      cell division cycle 2 (Cdc2), which directly phosphorylated recombinant Ubc9.
      Mat1a KO mice had higher phosphorylated (phospho)-Ubc9 levels, which normalized
      after SAMe treatment. SAMe and MTA treatment lowered Cdc2 mRNA and protein
      levels, as well as phospho-Ubc9 and protein sumoylation in liver, colon, and
      breast cancer cells. Serine 71 of Ubc9 was required for phosphorylation,
      interaction with Cdc2, and protein stability. Cdc2, Ubc9, and phospho-Ubc9 levels
      increased in human liver, breast, and colon cancers. CONCLUSION: Cdc2 expression
      is increased and Ubc9 is hyperphosphorylated in several cancers, and this
      represents a novel mechanism to maintain high Ubc9 protein expression that can be
      inhibited by SAMe and MTA.

PMID- 22407596
TI  - Differing Schwann cells and olfactory ensheathing cells behaviors, from
      interacting with astrocyte, produce similar improvements in contused rat spinal
      cord's motor function.
AB  - In recent years, cell behaviors of Schwann cells (SCs) and olfactory ensheathing
      cells (OECs) when interacting with astrocytes was appraised qualitatively in
      vitro and in spinal cord injury model of dorsal crush and transection and in
      normal white matter. In this study, with an attempt to select a candidate for
      cell-mediated repair of the spinal cord injury, SCs or OECs were transplanted
      into contused spinal cord in adult rats. The interaction with host astrocytes was
      assessed at 3 and 6 weeks after transplantation under light and electron
      microscope. The motor function of the rat was appraised with the BBB locomotor
      rating scale and cortical somatosensory evoked potentials (CSEP) recording.
      Within SCs cord, the astrocytes underwent proliferation and hypertrophy. The
      myelinated axons were separated into the groups by the glial membrane. Within
      OECs cord, astrocytes did not undergo the proliferation and hypertrophy. The
      myelinated axons were not divided into groups by the scar tissue. SCs graft,
      compared with OECs graft, induced more enhanced glial fibrillary acidic protein
      (GFAP) immunoreactivity with a distinct astroglial border between the normal and
      injured tissues. The distribution of SCs was more concentrated and less migrated
      than that of OECs. SCs induced weaker NF immunoreactivity and functional recovery
      compared to OECs, but no significant differences between the two groups was
      revealed by the statistical analysis. As we know, this is first time to compare
      behaviors of SCs and OECs in the contusion model, and the data indicates that
      although in vivo cell behaviors of SCs and OECs are different in interacting with
      astrocyte, both cell types can improve the motor function of the contused rats.

PMID- 22407597
TI  - Instantaneous detection of nonadherence: quality, strength, and weakness of an
      electronic prescription database.
AB  - BACKGROUND: The "personal electronic medicine profile" (PEM) is a Web-based tool
      for electronic prescription and monitoring of purchased medicine. It is based on
      the National Prescription Database and contains data on all prescriptions in
      Denmark. It includes information on time of drug purchase, number of tablets, and
      prescribed daily dosage. This allows calculation of the expected time for new
      purchases. PURPOSE: To study the accuracy of the PEM as a tool for monitoring
      drug nonadherence as compared with pill counts (PCs). METHODS: Five hundred
      eighty-three randomly selected elderly Danish citizens older than 65 years taking
      more than four drugs were studied. They were visited three times by a nurse who
      counted their medicine supply. Contingency table analysis was used to compare
      drug nonadherence calculated from PC with that revealed by PEM. For PC and PEM,
      an adherence level of at least 80% was defined as acceptable. RESULTS: PEM could
      not accurately process (non)adherence in 44% of all drugs. The probability of
      identifying drug nonadherence with PEM was low (negative predictive value 23%).
      Incomplete prescription information (34%) and inaccurate dosage registration
      (10%) were the major sources of error. CONCLUSION: PEM is inferior to PC for
      accurate monitoring of drug nonadherence. The inaccuracy is due to erroneous
      prescription information. PEM could be a powerful tool for electronic monitoring
      of drug nonadherence if prescription information was recorded uniformly and
      correctly. To increase the accuracy, we recommend informal free-text dosing
      instruction to be translated into a formal one by use of appropriate software
      such as library of phrases.

PMID- 22407598
TI  - Reconciling the risk of QT interval prolongation in antidepressants.

PMID- 22407600
TI  - Misconceptions regarding the association between Herbalife products and liver
      related case reports in Spain.

PMID- 22407603
TI  - Response to Teschke et al.

PMID- 22407604
TI  - Choosing an appropriate control group for an observational study design.

PMID- 22407606
TI  - Tailoring broadband antireflection on a silicon surface through two-step silver
      assisted chemical etching.
AB  - Combined nanostructure arrays with tailored structural profiles are presented
      (see picture, GN: graded nanostructure). These arrays exhibit a sharp decrease in
      reflectivity when submitted to strong sunlight irradiation, showing great
      potential for diverse applications, such as optical and electro-optical devices
      and other antireflection designs.

PMID- 22407607
TI  - Overcome by weakness.

PMID- 22407608
TI  - Integration of proteomics into systems biology of cancer.
AB  - Deciphering the complexity and heterogeneity of cancer, benefits from integration
      of proteomic level data into systems biology efforts. The opportunities available
      as a result of advances in proteomic technologies, the successes to date, and the
      challenges involved in integrating diverse datasets are addressed in this review.

PMID- 22407609
TI  - A one-step process for the antimicrobial finishing of textiles with crystalline
      TiO2 nanoparticles.
AB  - Titanium oxide (TiO(2)) nanoparticles (NPs) in their two forms, anatase and
      rutile, were synthesized and deposited onto the surface of cotton fabrics by
      using ultrasonic irradiation. The structure and morphology of the nanoparticles
      were analyzed by using characterization methods such as XRD, TEM, STEM, and EDS.
      The antimicrobial activities of the TiO(2)-cotton composites were tested against
      Escherichia coli (gram-negative) and Staphylococcus aureus (gram-positive)
      strains, as well as against Candida albicans. Significant antimicrobial effect
      was observed, mainly against Staphylococcus aureus. In addition, the combination
      of visible light and TiO(2) NPs showed enhanced antimicrobial activity.

PMID- 22407610
TI  - A chromosome 19 locus positively influences the number of retrieved oocytes
      during stimulated cycles in Brazilian women.
AB  - PURPOSE: To evaluate if several genetic loci that are associated with variation
      in normal menopause age and early menopause can account for a poor response to
      controlled ovarian stimulation. METHODS: A total of 71 patients age <=35 years
      old who were undergoing intracytoplasmic sperm injection were genotyped for four
      genetic variants that are associated with normal variation in menopausal age and
      early menopause. The patients were divided into two groups based upon treatment
      response: a poor responder group (PR group, n = 21) and a normal responder group
      (NR group, n = 50). The genetic variants rs244715, rs9379896, rs4806660 and
      rs16991615 were analyzed. RESULTS: There was no significant difference in the
      incidence of the genetic variants between the NR and PR group. The risk allele
      for the chromosome 19 variant (rs4806660) demonstrated a protective effect for a
      poor ovarian response. The presence of a risk allele was associated with an
      increased response to COS, which resulted in an elevated number of follicles
      (Coef: 2.54, P = 0.041) and retrieved oocytes (Coef: 1.41, P = 0.041).
      CONCLUSIONS: The genetic variants rs244715, rs9379896, rs4806660 and rs16991615
      are not risk factors for poor ovarian response in Brazilian women. In contrast,
      rs4806660 is associated with higher number of follicles and retrieved oocytes.
      rs4806660 may be associated with an increased response to gonadotrophin
      stimulation in this population.

PMID- 22407611
TI  - Development of a novel protocol for isolation and purification of human granulosa
      cells.
AB  - PURPOSE: To develop an optimal method of isolation and purification of human
      granulosa cells from ovarian follicular fluid. METHODS: Follicular fluid was
      collected from patients undergoing oocyte retrieval. A series of isolation and
      purification techniques was performed, involving density gradient centrifugation
      and use of different antibody-bead complexes. RESULTS: The highest percent yield
      of live purified granulosa cells came from density gradient centrifugation using
      sucrose polymer followed by positive selection of granulosa cells using primary
      antibody to MISRII and secondary antibody coupled to iron oxide beads.
      CONCLUSIONS: A novel protocol for granulosa cell purification has been developed
      yielding samples that are largely free of nondesirable cells. This protocol
      provides a purification solution, especially for patient samples that have
      significant RBC contamination.

PMID- 22407612
TI  - Fluorescence/bioluminescence resonance energy transfer techniques to study G
      protein-coupled receptor activation and signaling.
AB  - Fluorescence and bioluminescence resonance energy transfer (FRET and BRET)
      techniques allow the sensitive monitoring of distances between two labels at the
      nanometer scale. Depending on the placement of the labels, this permits the
      analysis of conformational changes within a single protein (for example of a
      receptor) or the monitoring of protein-protein interactions (for example, between
      receptors and G-protein subunits). Over the past decade, numerous such techniques
      have been developed to monitor the activation and signaling of G-protein-coupled
      receptors (GPCRs) in both the purified, reconstituted state and in intact cells.
      These techniques span the entire spectrum from ligand binding to the receptors
      down to intracellular second messengers. They allow the determination and the
      visualization of signaling processes with high temporal and spatial resolution.
      With these techniques, it has been demonstrated that GPCR signals may show
      spatial and temporal patterning. In particular, evidence has been provided for
      spatial compartmentalization of GPCRs and their signals in intact cells and for
      distinct physiological consequences of such spatial patterning. We review here
      the FRET and BRET technologies that have been developed for G-protein-coupled
      receptors and their signaling proteins (G-proteins, effectors) and the concepts
      that result from such experiments.

PMID- 22407613
TI  - Dual role of Toll-like receptors in asthma and chronic obstructive pulmonary
      disease.
AB  - During the last decade, significant research has been focused on Toll-like
      receptors (TLRs) in the pathogenesis of airway diseases. TLRs are pattern
      recognition receptors that play pivotal roles in the detection of and response to
      pathogens. Because of the involvement of TLRs in innate and adaptive immunity,
      these receptors are currently being exploited as possible targets for drug
      development. Asthma and chronic obstructive pulmonary disease (COPD) are chronic
      inflammatory airway diseases in which innate and adaptive immunity play an
      important role. To date, asthma is the most common chronic disease in children
      aged 5 years and older. COPD is prevalent amongst the elderly and is currently
      the fifth-leading cause of death worldwide with still-growing prevalence. Both of
      these inflammatory diseases result in shortness of breath, which is treated,
      often ineffectively, with bronchodilators and glucocorticosteroids. Symptomatic
      treatment approaches are similar for both diseases; however, the underlying
      immunological mechanisms differ greatly. There is a clear need for improved
      treatment specific for asthma and for COPD. This review provides an update on the
      role of TLRs in asthma and in COPD and discusses the merits and difficulties of
      targeting these proteins as novel treatment strategies for airway diseases. TLR
      agonist, TLR adjuvant, and TLR antagonist therapies could all be argued to be
      effective in airway disease management. Because of a possible dual role of TLRs
      in airway diseases with shared symptoms and risk factors but different
      immunological mechanisms, caution should be taken while designing pulmonary TLR
      based therapies.

PMID- 22407615
TI  - Conus venom peptide pharmacology.
AB  - Conopeptides are a diverse group of recently evolved venom peptides used for prey
      capture and/or defense. Each species of cone snails produces in excess of 1000
      conopeptides, with those pharmacologically characterized (~ 0.1%) targeting a
      diverse range of membrane proteins typically with high potency and specificity.
      The majority of conopeptides inhibit voltage- or ligand-gated ion channels,
      providing valuable research tools for the dissection of the role played by
      specific ion channels in excitable cells. It is noteworthy that many of these
      targets are found to be expressed in pain pathways, with several conopeptides
      having entered the clinic as potential treatments for pain [e.g., pyroglutamate1
      MrIA (Xen2174)] and one now marketed for intrathecal treatment of severe pain
      [ziconotide (Prialt)]. This review discusses the diversity, pharmacology,
      structure-activity relationships, and therapeutic potential of cone snail venom
      peptide families acting at voltage-gated ion channels (omega-, MU-, MUO-, delta-,
      iota-, and kappa-conotoxins), ligand-gated ion channels (alpha-conotoxins, sigma
      conotoxin, ikot-ikot, and conantokins), G-protein-coupled receptors (rho
      conopeptides, conopressins, and contulakins), and neurotransmitter transporters
      (chi-conopeptides), with expanded discussion on the clinical potential of sodium
      and calcium channel inhibitors and alpha-conotoxins. Expanding the discovery of
      new bioactives using proteomic/transcriptomic approaches combined with high
      throughput platforms and better defining conopeptide structure-activity
      relationships using relevant membrane protein crystal structures are expected to
      grow the already significant impact conopeptides have had as both research probes
      and leads to new therapies.

PMID- 22407617
TI  - Novel pharmacological approaches to the treatment of type 2 diabetes.
AB  - The huge increase in type 2 diabetes is a burden worldwide. Many marketed
      compounds do not address relevant aspects of the disease; they may already
      compensate for defects in insulin secretion and insulin action, but loss of
      secreting cells (beta-cell destruction), hyperglucagonemia, gastric emptying,
      enzyme activation/inhibition in insulin-sensitive cells, substitution or
      antagonizing of physiological hormones and pathways, finally leading to secondary
      complications of diabetes, are not sufficiently addressed. In addition, side
      effects for established therapies such as hypoglycemias and weight gain have to
      be diminished. At present, nearly 1000 compounds have been described, and
      approximately 180 of these are going to be developed (already in clinical
      studies), some of them directly influencing enzyme activity, influencing
      pathophysiological pathways, and some using G-protein-coupled receptors. In
      addition, immunological approaches and antisense strategies are going to be
      developed. Many compounds are derived from physiological compounds (hormones)
      aiming at improving their kinetics and selectivity, and others are chemical
      compounds that were obtained by screening for a newly identified target in the
      physiological or pathophysiological machinery. In some areas, great progress is
      observed (e.g., incretin area); in others, no great progress is obvious (e.g.,
      glucokinase activators), and other areas are not recommended for further
      research. For all scientific areas, conclusions with respect to their impact on
      diabetes are given. Potential targets for which no chemical compound has yet been
      identified as a ligand (agonist or antagonist) are also described.

PMID- 22407618
TI  - PDT in non-surgical treatment of periodontitis in HIV patients: a split-mouth,
      randomized clinical trial.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the clinical and
      microbiological effect of photodynamic therapy (PDT) in the non-surgical
      treatment of periodontitis in HIV patients. METHODS: Twelve HIV patients from the
      CEAPE/UNIP, Brazil, with periodontitis were included in this 6-month, split
      mouth, double-blind, controlled clinical trial. Patients were placed in the
      following groups: Group SRP-scaling and root planning with an ultrasonic device
      (SRP); and Group SRP + PDT-SRP associated with a course of PDT with a diode laser
      with a wavelength of 660 nm and 0.03 W power associated with methylene blue 0.01%
      lasting 133 seconds. All clinical measurements (periodontal probing depth (PPD),
      gingival recession (GR), clinical attachment level (CAL), full-mouth plaque index
      (FMPI), bleeding score (FMBS)), and microbiological parameters (detection of
      Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), and Aggregatibacter
      actinomycetemcomitans (Aa)) were assessed at baseline and at 45 days, and 3 and 6
      months after therapy. The ANOVA/Tukey was used for statistical analysis (alpha =
      5%). RESULTS: There were no differences in any of the investigated parameters
      observed at baseline in the two groups (P > 0.05). Moreover, participants in the
      SRP + PDT group presented a higher PPD reduction and CAL gain than those in the
      SRP group at 45 days and 3 and 6 months. At 6 months, sites receiving SRP + PDT
      showed a significant PPD reduction of 1.4 +/- 0.5 mm, while those in the SRP
      group showed a 0.3 +/- 0.8 mm reduction (P < 0.05). The CAL gain at the sixth
      month was 1.3 +/- 0.5 mm and 0.2 +/- 0.7 mm for participants in the SRP + PDT and
      SRP groups, respectively (P < 0.05). Microbiologically, both therapies presented
      a reduction in the detection of Pg, Tf, and Aa, and there was no difference
      between them (P > 0.05). CONCLUSION: We concluded that PDT therapy used
      adjunctively to SRP could promote additional benefits in the treatment of HIV
      associated periodontitis.

PMID- 22407619
TI  - [Web site of La Tunisie Medicale was created two years ago ...].
AB  - BACKGROUND: La Tunisie Medicale, official journal of Tunisian Society for Medical
      Sciences and Tunisian Medical Organization, born in 1903 with ISSN number 0041
      4131and INIST code 4691 of French Pascal database, had since September 2009 its
      website : www.latunisiemedicale.com AIM: To assess the editorial policy of "La
      Tunisie Medicale" METHODS: A descriptive analysis was performed to evaluate
      different categories of articles and number of papers written with English
      language. mdweb society, which created the website site www.latunisiemedicale.com
      , planned to have instantaneously a descriptive analysis concerning the number of
      consultants per article. The site www.scopus.com helped us to have the number of
      articles citations which was useful to calculate Impact Factor (IF). National
      Center for Biotechnology Information (NCBI) of National Library of Medicine
      provided monthly number of hits. RESULTS: Number of published articles increased
      regularly to reach 250 and 300 between 2009 and 2011. Beside original articles,
      cases report, overviews, continuing medical education and editorials, we
      introduced systematic reviews of literature, letters to editors, historical
      notes, section reserved for images in clinical practice, point of view, technical
      novelty and section for " Pro & Cons" in which readers could present their
      opinions with reply of authors. Articles written in English have increased to
      reach the number of 60 between 2010 and 2011. Visitors number of "la Tunisie
      Medicale" website, from 195 countries, was 465 596 between January 1st 2011 and
      December 22nd 2011. Half of consultants (51.06%) came from several sources such
      as "Google/organic" and "ncbi.nlm.nih.gov/ referral". Number of visits from NCBI
      was about 3000 per month from June 2010 to December 2011. The ten first visited
      articles concerned sexual organ and tuberculosis. Articles citations of
      "laTunisie Medicale" are in constant progress and Impact Factor, increased from
      0.054 in 2004 to 0.277 in 2011. CONCLUSION: We succeeded to increase the number
      of articles written in English. Results are interesting Impact Factor of 2011 is
      0,277; however we should be modest because we still have a very long way, we
      should help authors to perform systematic reviews with a sound methodology.

PMID- 22407620
TI  - [Efficacy and safety of Adalimumab in Crohn's disease].
AB  - BACKGROUND: Adalimumab is the first subcutaneously self administered fully human
      anti-TNFa. AIM: To determine efficacy and safety of Adalimumab therapy in Crohn
      disease. METHODS: Literature review. RESULTS: Adalimumab has been evaluated for
      its effect in inducing and maintaining remission and its steroid-sparing effect
      of refractory Crohn's disease. In addition, it offers a significant treatment
      option in patients who have lost response to or become intolerant to Infliximab.
      Results also suggest efficacy of Adalimumab in fistulising Crohn's disease but
      more studies are needed. Adalimumab was well tolerated and studies show that all
      anti-TNF inhibitors have similar safety profiles.

PMID- 22407616
TI  - Brain-derived neurotrophic factor and neuropsychiatric disorders.
AB  - Brain derived neurotrophic factor (BDNF) is the most prevalent growth factor in
      the central nervous system (CNS). It is essential for the development of the CNS
      and for neuronal plasticity. Because BDNF plays a crucial role in development and
      plasticity of the brain, it is widely implicated in psychiatric diseases. This
      review provides a summary of clinical and preclinical evidence for the
      involvement of this ubiquitous growth factor in major depressive disorder,
      schizophrenia, addiction, Rett syndrome, as well as other psychiatric and
      neurodevelopmental diseases. In addition, the review includes a discussion of the
      role of BDNF in the mechanism of action of pharmacological therapies currently
      used to treat these diseases, such antidepressants and antipsychotics. The review
      also covers a critique of experimental therapies such as BDNF mimetics and
      discusses the value of BDNF as a target for future drug development.

PMID- 22407621
TI  - [Compression treatment for burned skin].
AB  - BACKGROUND: The regularity of a compressive knit is defined as its ability to
      perform its function in a burnt skin. This property is essential to avoid the
      phenomenon of rejection of the material or toxicity problems But: Make knits
      biocompatible with high burnet of human skin. METHODS: We fabric knits of elastic
      material. To ensure good adhesion to the skin, we made elastic material,
      typically a tight loop knitted. The Length of yarn absorbed by stitch and the raw
      matter are changed with each sample. The physical properties of each sample are
      measured and compared. Surface modifications are made to these samples by
      impregnation of microcapsules based on jojoba oil. RESULTS: Knits are compressif,
      elastic in all directions, light, thin, comfortable, and washable for hygiene
      issues. In addition, the washing can find their compressive properties. The
      Jojoba Oil microcapsules hydrated the human burnet skin. This moisturizer is used
      to the firmness of the wound and it gives flexibility to the skin. CONCLUSION:
      Compressive Knits are biocompatible with burnet skin. The mixture of natural and
      synthetic fibers is irreplaceable in terms comfort and regularity.

PMID- 22407614
TI  - Serotonin and blood pressure regulation.
AB  - 5-Hydroxytryptamine (5-HT; serotonin) was discovered more than 60 years ago as a
      substance isolated from blood. The neural effects of 5-HT have been well
      investigated and understood, thanks in part to the pharmacological tools
      available to dissect the serotonergic system and the development of the
      frequently prescribed selective serotonin-reuptake inhibitors. By contrast, our
      understanding of the role of 5-HT in the control and modification of blood
      pressure pales in comparison. Here we focus on the role of 5-HT in systemic blood
      pressure control. This review provides an in-depth study of the function and
      pharmacology of 5-HT in those tissues that can modify blood pressure (blood,
      vasculature, heart, adrenal gland, kidney, brain), with a focus on the autonomic
      nervous system that includes mechanisms of action and pharmacology of 5-HT within
      each system. We compare the change in blood pressure produced in different
      species by short- and long-term administration of 5-HT or selective serotonin
      receptor agonists. To further our understanding of the mechanisms through which 5
      HT modifies blood pressure, we also describe the blood pressure effects of
      commonly used drugs that modify the actions of 5-HT. The pharmacology and
      physiological actions of 5-HT in modifying blood pressure are important, given
      its involvement in circulatory shock, orthostatic hypotension, serotonin syndrome
      and hypertension.

PMID- 22407622
TI  - [Kaposi's sarcoma: epidemiological, clinical, anatomopathological and therapeutic
      features in 75 patients].
AB  - BACKGROUND: Kaposi's sarcoma (KS) is a mutifocal angiogenic process characterized
      by cellular and vascular proliferation. AIM: To identify the epidemio-clinical,
      histological and therapeutic features of KS. METHODS: Retrospective study of 75
      cases of KS at the dermatology department of Rabta hospital in Tunis during a
      period of 25 years (1982-2007). RESULTS: Three epidemio-clinical forms of KS were
      observed in our study: the classic KS (70 cases), the AIDS-related KS (4 cases)
      and the iatrogenic KS (1 case). The mean age of our patients at diagnosis was
      69.16 years with a sex ratio of 2.33. Elective site of cutaneous lesions in the
      classic KS was the limbs (87.1%). The cephalic part was concerned in 17.1% of
      cases. Mucosal involvement was found in 28.5% of patients. Extra dermatological
      localizations of KS were observed in 32.9%. CONCLUSION: Our study identified some
      epidemio-clinical features of the classic KS especially the high frequency of
      mucosal and cephalic involvement as well as extra dermatological localizations.
      Thus further exploration is required even without alarm signs.

PMID- 22407623
TI  - [Ovarian drilling for the treatment of infertility with dystrophic ovaries].
AB  - BACKGROUND: Dystrophic ovaries represent the main cause of female infertility in
      Tunisia. AIM: To assess the contribution of ovarian drilling in the treatment of
      infertility in patients with ovarian dystrophy. METHODS: A retrospective study of
      23 patients with dystrophic ovaries that have benefited through their
      subfertility of laparoscopic ovarian drilling, in the gynecology-obstetrics
      hospital Mahmoud EL Matri, Ariana, Tunisia. Our study spans a period of 3 years
      from January 2004 to December 2006. RESULTS: Among the 23 patients who underwent
      drilling for clomiphene citrate resistance, 9 have been pregnant. The average age
      of patients having had a pregnancy after ovarian drilling was 29.6 years, the
      average delay was 7.1mois. Regarding prognostic factors, only infertility's
      duration lower than 3 years was predictive of a good result. CONCLUSION: Ovarian
      drilling is an interesting alternative to induction by FSH for patients with
      dystrophic ovaries.

PMID- 22407624
TI  - [Prevalence of bone loss in adult celiac disease and associated factors: a
      control case study].
AB  - BACKGROUND: Bone loss in celiac disease (CD) is important and is associated to
      increased risk of fractures. The determining factors of this Bone loss and the
      osteoporosis fracture during this disease remain still unknown. The bone
      remodeling parameters seem to play it an important role. AIM: Through a
      transverse study including 30 patients with adult CD and 30 witnesses, we
      estimated bone mineral density (BMD) profile of these patients and determined
      associated factors to the bone loss. METHODS: Patients and witnesses benefited
      from an BMD measure, serum calcium and phosphore, alkaline phosphatasis,
      parathormone and hydroxyvitamin D dosage, bone remodeling parameters containing
      the osteocalcin, Propeptide N-terminal of the type I procollagen, BTelopeptide C
      terminal ( B-CTX) of the type I procollagen I (bloody and urine CrossLaps). The
      patients benefited from a malabsorption bilan, a radiological examination of
      spine and an evaluation of the adhesion to the regime without gluten with a
      histological control. RESULTS: Our population consists of 3 men (10 %) and 27
      women (90 %) with an average age of 30.4 years (19-50 years). The average delay
      of the diagnosis of the MC is of 46.7 months. The alkaline phosphatases, the P1NP
      and the bloody crossLaps were more raised at the patient's with regard to the
      witnesses with respectively p=0.038, p=0.041 and p=0.021. The parathormone was
      also more raised at the patients but without significant difference 67.8 vs 53.8
      ng / l. The DMO is low at 21 patients (70 %) versus 2 witnesses only (6.6 %),
      with an osteoporosis in 3 patients (10 %) and an osteopenia in 18 patients (60
      %). Factors associated to the BMD decline are low body mass index, nulliparity,
      diagnostic delay > to 2 years, the malabsorption syndrome, exaggerated
      intraepithelial lymphocytosis at the time of the histological control, an
      increase of bone remodeling parameters notably the alkaline phosphatasis,
      osteocalcin and bloody CrossLaps. While the BMD is more raised at the patient's
      having followed gluten regimens during more than 5 years. The age, the sex, the
      symptomatic character or not of the disease, the parathormone, hydroyviamin D and
      fractures are not correlated to the BMD profile patients. CONCLUSION: The bone
      loss is more frequent during the adult CD than in the general population. His
      research has to become integrated into the coverage of this disease notably in
      the presence of risk factors. The absence of correlation between BMD loss and
      fractures underlines the importance of others factors in determining of bone
      fragility during this affection.

PMID- 22407625
TI  - [Delivery in twin pregnancies. The experience of the obstetrics department of
      Aziza Othmana's Hospital, about 117 cases].
AB  - BACKGROUND: The conduct and delivery of twin pregnancies are interspersed with as
      well as maternal fetal and neonatal complications. The obstetrician is faced with
      the birth of 2 children often fragile and a uterus often exposed to dynamic
      dystocia. AIM: To study the maternal and newborn morbidity and mortality in
      twins, in order to clear the optimal route of delivery in such circumstances.
      METHODS: A retrospective study over a period of 3 years (1 January 2005 to
      December 31, 2007), about 117 twin pregnancies. Inclusion criteria were a term
      exceeding 28 weeks and fetuses alive. We analyzed maternal complications during
      and after delivery and neonatal complications. RESULTS: Maternal complications
      were significantly more frequent in case of caesarean section. The frequency of
      perinatal complications (Apgar score, respiratory distress, immediate neonatal
      resuscitation and neonatal intensive care unit transfer) in the first twin was
      not influenced by the route of delivery as opposed to the second twin which Apgar
      score's alters when vaginally. The newborns of low birth weight (<1,500 Kg) and
      those whose term was less than 32 weeks were more at risk of an Apgar score <7
      (at 1 and 5 minutes), respiratory complications, need for immediate resuscitation
      and transfer to intensive care and that statistically significant both for the
      1st and the 2nd twins. CONCLUSION: The twins pregnancies' morbidity appears to be
      more related to prematurity and intra uterine growth retardation) more than to
      the mode of delivery and hence the interest to detect and prevent its anomalies.
      It seems that vaginal delivery has a deleterious effect at least for the second
      twin but cesarean section doesn't seem to be the solution. Better learning
      techniques and obstetric maneuvers would reduce morbidity.

PMID- 22407626
TI  - Liver injuries in children: the role of selective non-operative management.
AB  - BACKGROUND: Trauma remains the leading cause of mortality in the pediatric
      population. Liver injuries occur commonly in blunt abdominal trauma. AIM: To
      assess the selective non-operative management of liver injuries in children.
      METHODS: A retrospective review of 51 patients with a discharge diagnosis of
      traumatic liver injuries at Tunis Children's Hospital, over a 14-year period from
      1996 to 2009. RESULTS: We identified 51 patients with liver trauma. The median
      age was 7 years. Boys accounted for 58% (n= 30), and the most common cause was
      traffic accident. Head injuries were the most common associated injuries. Forty
      nine patients (96%) required non-operative management without complications. The
      mean in-hospital stay was 10 days in this group. The ultrasound demonstrated
      complete resolution and healing after 3-6 months. Two patients underwent surgery
      for hemodynamic instability. The mortality rate was 0.2 %. CONCLUSION: Safe, non
      operative management involves careful serial examination, a CT scanning facility
      and close monitoring of the patient in a fully equipped high-dependency unit with
      trained staff to run it. Even though most patients can be treated non-operatively
      the challenge is to identify the severely injured child early and institute
      aggressive resuscitation and expedite laparotomy.

PMID- 22407627
TI  - Risk factors associated with pancreatic fistula after distal pancreatectomy.
AB  - BACKGROUND: Pancreatic leak (PL) remains a major cause of postoperative morbidity
      in patients undergoing pancreatic resection. AIM: To identify risk factors
      related to pancreatic fistula in patients undergoing distal pancreatectomy (DP).
      METHODS: 35 patients underwent DP during a 10-year period (2000- 2009).
      Informations regarding diagnosis, operative details, and perioperative morbidity
      and mortality were collected. Nine risk factors were examined. RESULTS:
      Indications for DP included primary pancreatic disease (n=23; 66 %) and non
      pancreatic disease (n = 12; 34 %). Postoperative morbidity rate was 43 % and none
      patient died. No patients required a reoperation. Pancreatic fistula was occurred
      in 11 patients (31 %). On univariate analysis, incidence of pancreatic fistula
      rate was not significantly associated with these risk factors: pathology, use of
      prophylactic octreotide therapy, concomitant splenectomy, additional procedures,
      intra operative bleeding and texture of pancreatic parenchyma. We observed
      significant statistical difference between male and female, 47 % of females
      experienced a pancreatic fistula, while 17 % males developed a pancreatic leakage
      (p =0.05). The role of the technique of pancreatic stump closure in the
      development of pancreatic leak remains unclear because of the few number of
      patients on who we used stapler. CONCLUSION: The rate of pancreatic fistula after
      left pancreatectomy is 31 %. The female was identified as a risk factor for
      occurrence of pancreatic fistula after left pancreatectomy. The role implicated
      in the use of a mechanical claw for the treatment of pancreatic stump requires a
      larger number of patients to conclude. The body mass index has not been studied
      in our series.

PMID- 22407628
TI  - [Usefulness of magnetic resonance imaging in the diagnosis of early rheumatoid
      arthritis: a prospective study of 20 cases].
AB  - BACKGROUND: Diagnosing early rheumatoid arthritis is difficult and radiographic
      signs are often late. MRI detects erosions at an early stage and visualizes
      synovitis, bone edema and tenosynovitis. AIM: To assess the value of MRI for
      diagnosis of early forms of rheumatoid arthritis. METHODS: Prospective study
      involving 20 patients who had non erosive rheumatoid arthritis lasting for less
      than 2 years. MRI of the hand was performed by sequences coronal and axial T1
      weighted, T2 with saturated fat signal (FatSat) FatSat and T1 with gadolinium
      injection. RESULTS: The median age of patients was 52 years and sex ratio M/F of
      0.05. The median disease duration was 9 months. Ten patients had antibodies Anti
      Cyclic citrullinated protein positive. The MRI was abnormal in 75% of patients.
      This review found 36 erosions which 50% were in carpal bones, 55 joints with
      synovitis mainly localized midcarpal and metacarpophalangeal. Bone edema was
      found mainly in carpal bones. Tenosynovitis affected most frequently the flexor
      tendons. Seventy percent of patients without anti-Cyclic citrullinated protein
      had a pathological MRI. CONCLUSION: MRI has an important role in detecting
      infraradiological lesions in early RA. This contributes to early diagnosis and
      initiation effective treatment.

PMID- 22407629
TI  - [Thromboembolic complications of childhood nephrotic syndrome].
AB  - BACKGROUND: Vascular thrombosis in the childhood nephrotic syndrome is a rare
      event. It poses major diagnostic and therapeutic problems. The prognosis depends
      on early diagnosis and on precocious anticoagulation. The risk of extension of
      thrombosis and pulmonary embolism is real. AIMS: To consider the major thrombotic
      events associated with childhood nephrotic syndrome and to establish an
      appropriate preventive approach based on objective clinical and laboratory
      parameters. METHODS: This is a retrospective study of all cases of patients
      suffering from idiopathic nephrotic syndrome, during a period of 20 years,
      starting from January 1990 to December 2009. We selected six patients with
      vascular thrombosis. The diagnosis was confirmed by appropriate radiological
      investigation. RESULTS: Six cases of vascular thrombosis were identified among
      260 cases of nephrotic syndrome collected during the period study. Patients are
      divided into five boys and one girl. The mean age was 13.3 years. The
      localisation of thrombosis is venous in all cases. One patient presented a
      massively fatal pulmonary embolism. Sinovenous thrombosis has been objectified in
      3 patients who were all treated with a good therapeutic response. CONCLUSION:
      vascular thrombosis remains one of the most serious complications of nephrotic
      syndrome in children. Early diagnosis and precocious anticoagulation are
      essential for preventing the extension of thrombosis.

PMID- 22407630
TI  - [Medical demography in Tunisia: current situation and perspectives].
AB  - BACKGROUND: Health human resources management is one of the important
      determinants of health care access equity. AIMS: To analyse the trend of Tunisian
      medical density during 2000-2009 and to predict its situation by 2024. METHODS:
      Current medical density was calculated using Bar Council of Physicians of Tunisia
      database. Medical density was calculated and analysed for the period 2000-2009
      then modelled by 2024 (estimate of needs and supply). RESULTS: The active medical
      density raised by 36% during the period 2000-2009 with a higher increase for
      specialists. The proportion of non-active physicians rose from 4.6% to 15.2% in
      2009. Increasing feminization of medical density and persistence of its regional
      disparities. By the year 2024, 217 physicians for 100,000 inhabitants would be
      required while the supply would correspond to 212/100 000 inhabitants.
      CONCLUSION: medical human resources have indeed globally improved. However, some
      lacks remain and adequate measures are required, based on a rational planning
      directed to satisfy the population needs and to allow health equity.

PMID- 22407631
TI  - The natural history of hepatitis B virus cirrhosis after the first hepatic
      decompensation in Tunisia.
AB  - AIM: To define the natural long term course of viral B cirrhosis after the onset
      of hepatic decompensation and to determine the predictive factors of death.
      METHODS: Retrospective longitudinal study including 77 cases of viral B cirrhosis
      among 192 consecutive patients with cirrhosis, hospitalized between 1997 and 2005
      for the first hepatic decompensation. All those patients were followed- up until
      death or until December 2006. The probability of survival after the first hepatic
      decompensation was calculated using the Kaplan Meier method. The predictive
      factors of death were determined through univariate and multivariate analyses
      with the Cox regression model. RESULTS: Fifty four men and 23 women with an
      average age of 54+/-14.9 years were hospitalized for the first decompensation of
      the viral B cirrhosis. The 77 patients had been under observation for an average
      period of 24.2 +/-21.1 months. During that time 64% among them died. The
      probability of survival after decompensation was 47% in 2 years and 22 % in 5
      years. During follow- up, ascites was the most frequent decompensation (85%)
      followed by hepatic encephalopathy (38 %), variceal hemorrhage (34 %), jaundice
      (30%), hepato renal syndrome (27%), hepatocellular carcinoma (21%), and
      spontaneous bacterial peritonitis (14%). At univariate analysis four factors were
      predictive of death: Child Pugh C score (p=0.009), hepatocellular carcinoma
      (p=0.01), rate of serum gammaglobulin superior to18g / l (p=0.008) and
      prothrombin time inferior to 50 % (p=0.02). According to the multivariate
      analysis only the rate of serum gammaglobulin superior to 18g /l was an
      independent predictive factor of mortality (p=0,001) with IC (95 %) [1.623 -
      5.88]. CONCLUSION: In Tunisia, the prognosis of viral B cirrhosis after the first
      decompensation is bad, because a patient on 5 only was able to survive beyond 5
      years. Ascites is the most frequent decompensation. Only the rate of serum
      gammaglobulin superior to 18g / l is an independent predictive factor of
      mortality.

PMID- 22407632
TI  - [Melanoma of the hand].

PMID- 22407633
TI  - Paraganglioma of the nasal cavity.

PMID- 22407634
TI  - [Iatrogenic chest and face opacities!].

PMID- 22407635
TI  - Familial dilated cardiomyopathy associated with celiac disease.

PMID- 22407636
TI  - Sarcomatoid carcinoma of the urinary bladder.

PMID- 22407637
TI  - [Colonovesical fistula complicating colonic diverticulitis].

PMID- 22407638
TI  - Myoid differentiation in dermatofibrosarcoma protuberans.

PMID- 22407639
TI  - [Primary peritoneal amyloidosis revealed by an isolated ascitis and associated
      portal thrombosis secondary to resistance of activated C protein].

PMID- 22407640
TI  - [Retiform Sertoli-Leydig tumor with heterologous mucinous differentiation].

PMID- 22407641
TI  - [Gastric adenocarcinoma producing alpha-fetoprotein].

PMID- 22407642
TI  - Nutcracker syndrome as an incidental finding on computed tomography scan after
      blunt abdominal trauma.
AB  - BACKGROUND: The nutcracker syndrome refers to compression of the left renal vein
      between the aorta and the superior mesenteric artery. It may be asymptomatic for
      long period and constitute casual findings. AIM: To report a new case diagnosed
      by radiological exploration after an abdominal trauma. The diagnosis and
      treatment of nutcracker syndrome are discussed. CASE: A 32-year-old man was a
      victim of traffic accident causing leg and abdominal trauma. Three days after
      orthopedic surgery, he presented an isolated gross hematuria. Abdominal computed
      tomography showed that the left renal vein was compressed between the aorta and
      the superior mesenteric artery. The diagnosis of nutcracker syndrome was
      established. Surveillance was indicated with excellent evolution. CONCLUSION: The
      nutcracker syndrome is a rare entity. It may be asymptomatic. Its diagnosis is
      the privilege of medical imaging. Its treatment is controversial and should be
      discussed case by case.

PMID- 22407643
TI  - First case of subcutaneous dermatomycoses in a Tunisian renal transplant patient.
AB  - BACKGROUND: Dermatophytes are keratinophilic and usually infect the corneal layer
      of the epidermis and appendages On the occasion of immunosuppression, such as
      solid organ transplant, they can invade deeper tissues or cause an infection of
      the skin and subcutaneous disseminated. AIM: To report the first observation of
      subcutaneous dematophytosis in a Tunisian renal transplant patient. CASE REPORT:
      A 29-year-old man had an erythematous lesion of 2 cm at the front of the left
      leg. He was treated with prednisone and tacrolimus. The skin lesion was has been
      neglected. The outcome was the occurrence of oozing whose mycological examination
      showed numerous hyphae and culture was positive for Microsporum canis. Initial
      treatment was voriconazole, but an interaction with tacrolimus has shortened the
      duration of treatment to 1 month. Three months later, the lesion became deeper,
      and then a biopsy was performed. The mycological examination showed the same
      appearance, previously described. The patient was put on fluconazole by adjusting
      the doses of tacrolimus and then underwent surgical excision of the lesions. The
      evolution after 4 months of antifungal treatment was favorable. CONCLUSION: The
      increasing incidence of immunosuppressive therapy has given rise to unusual
      clinical forms of invasive and sometimes serious fungal agents whose
      pathogenicity is usually limited. Clinicians should be mindful of superficial
      fungal infections of the skin in a renal transplant patient.

PMID- 22407644
TI  - Comparative analysis of cerebrovascular resistance in fetuses with single
      ventricle congenital heart disease.
AB  - OBJECTIVE: We sought to determine whether the presence or absence of aortic
      obstruction impacts cerebrovascular resistance in fetuses with single-ventricle
      (SV) congenital heart disease (CHD). METHODS: Pulsatility indices (PIs) were
      recorded for the middle cerebral artery (MCA) and the umbilical artery (UA) from
      18 to 40 weeks' gestation in 59 fetuses (163 examinations) with SV-CHD with
      unobstructed aortic flow, yet decreased pulmonary flow, in 72 fetuses (170
      examinations) with obstructed aortic flow and hypoplastic left heart syndrome
      (HLHS) and in 92 normal fetuses (92 examinations). The cerebral-to-placental
      resistance (CPR) was calculated as the MCA-PI/UA-PI. Z-scores were generated for
      the MCA-PI and the UA-PI in order to make comparisons independent of gestational
      age. Statistical analyses were performed using one-way ANOVA with post-hoc
      testing. Trends in these variables over the course of gestation were assessed
      using linear regression and univariate ANOVA. RESULTS: The MCA-PI and the CPR
      were significantly lower in SV fetuses with aortic obstruction compared with SV
      fetuses with pulmonary obstruction and with normal fetuses. Moreover, the MCA-PI
      decreased significantly for SV fetuses with aortic obstruction over the course of
      gestation. In contrast, the MCA-PI was higher over the course of gestation in SV
      fetuses with pulmonary obstruction compared with normal fetuses. CONCLUSION: In
      fetuses with SV-CHD, cerebrovascular resistance varies substantially between
      fetuses with and without aortic obstruction. Compared with normal fetuses,
      cerebrovascular resistance is decreased in SV fetuses with aortic obstruction,
      yet increased in SV fetuses with pulmonary obstruction. In fetuses with SV
      physiology, inherent differences in cerebral blood flow may underlie postnatal
      neurodevelopmental outcomes.

PMID- 22407645
TI  - Gene expression in Citrus sinensis fruit tissues harvested from huanglongbing
      infected trees: comparison with girdled fruit.
AB  - Distribution of viable Candidatus Liberibacter asiaticus (CaLas) in sweet orange
      fruit and leaves ('Hamlin' and 'Valencia') and transcriptomic changes associated
      with huanglongbing (HLB) infection in fruit tissues are reported. Viable CaLas
      was present in most fruit tissues tested in HLB trees, with the highest titre
      detected in vascular tissue near the calyx abscission zone. Transcriptomic
      changes associated with HLB infection were analysed in flavedo (FF), vascular
      tissue (VT), and juice vesicles (JV) from symptomatic (SY), asymptomatic (AS),
      and healthy (H) fruit. In SY 'Hamlin', HLB altered the expression of more genes
      in FF and VT than in JV, whereas in SY 'Valencia', the number of genes whose
      expression was changed by HLB was similar in these tissues. The expression of
      more genes was altered in SY 'Valencia' JV than in SY 'Hamlin' JV. More genes
      were also affected in AS 'Valencia' FF and VT than in AS 'Valencia' JV. Most
      genes whose expression was changed by HLB were classified as transporters or
      involved in carbohydrate metabolism. Physiological characteristics of HLB
      infected and girdled fruit were compared to differentiate between HLB-specific
      and carbohydrate metabolism-related symptoms. SY and girdled fruit were smaller
      than H and ungirdled fruit, respectively, with poor juice quality. However,
      girdling did not cause misshapen fruit or differential peel coloration.
      Quantitative PCR analysis indicated that many selected genes changed their
      expression significantly in SY flavedo but not in girdled flavedo. Mechanisms
      regulating development of HLB symptoms may lie in the host disease response
      rather than being a direct consequence of carbohydrate starvation.

PMID- 22407647
TI  - Pathways and fluxes: exploring the plant metabolic network.
AB  - The transition from a pathway-centred view of plant metabolism to a network-wide
      perspective is still incomplete. Further progress in this direction requires
      tools to facilitate the structural description of the network on the basis of
      fully annotated genomes, techniques for modelling the properties of the network,
      and experimental methods for constraining the models and verifying their outputs.
      It also requires a focus on metabolic flux as the key to understanding the
      regulation of metabolic activity and the relationship between the inputs and
      outputs of the network. Progress is being made on several fronts and this Special
      Issue on 'Pathways and fluxes: exploring the plant metabolic network' describes
      current developments in the genomic reconstruction of metabolic networks, the
      application of flux-balance analysis to such networks, kinetic modelling, and
      both steady-state-and non-steady state isotope-based measurements of multiple
      fluxes in the network of central carbon metabolism. The papers also highlight
      insights that can be obtained from pathway analysis, particularly in relation to
      the thermodynamic and kinetic efficiency of the predicted and observed flux
      distributions.

PMID- 22407646
TI  - Live imaging of intra- and extracellular pH in plants using pHusion, a novel
      genetically encoded biosensor.
AB  - Changes in pH are now widely accepted as a signalling mechanism in cells. In
      plants, proton pumps in the plasma membrane and tonoplast play a key role in
      regulation of intracellular pH homeostasis and maintenance of transmembrane
      proton gradients. Proton transport in response to external stimuli can be
      expected to be finely regulated spatially and temporally. With the ambition to
      follow such changes live, a new genetically encoded sensor, pHusion, has been
      developed. pHusion is especially designed for apoplastic pH measurements. It was
      constitutively expressed in Arabidopsis and targeted for expression in either the
      cytosol or the apoplast including intracellular compartments. pHusion consists of
      the tandem concatenation of enhanced green fluorescent protein (EGFP) and
      monomeric red fluorescent protein (mRFP1), and works as a ratiometric pH sensor.
      Live microscopy at high spatial and temporal resolution is highly dependent on
      appropriate immobilization of the specimen for microscopy. Medical adhesive often
      used in such experiments destroys cell viability in roots. Here a novel system
      for immobilizing Arabidopsis seedling roots for perfusion experiments is
      presented which does not impair cell viability. With appropriate immobilization,
      it was possible to follow changes of the apoplastic and cytosolic pH in mesophyll
      and root tissue. Rapid pH homeostasis upon external pH changes was reflected by
      negligible cytosolic pH fluctuations, while the apoplastic pH changed
      drastically. The great potential for analysing pH regulation in a whole-tissue,
      physiological context is demonstrated by the immediate alkalinization of the
      subepidermal apoplast upon external indole-3-acetic acid administration. This
      change is highly significant in the elongation zone compared with the root hair
      zone and control roots.

PMID- 22407648
TI  - Use of the correct heat conduction-convection equation as basis for heat-pulse
      sap flow methods in anisotropic wood.
AB  - Heat-pulse methods to determine sap flux density in trees are founded on the
      theory of heat conduction and heat convection in an isotropic medium. However,
      sapwood is clearly anisotropic, implying a difference in thermal conductivity
      along and across the grain, and hence necessitates the theory for an anisotropic
      medium. This difference in thermal conductivities, which can be up to 50%, is,
      however, not taken into account in the key equation leading to the currently
      available heat-pulse methods. Despite this major flaw, the methods remain
      theoretically correct as they are based on derivations of the key equation,
      ruling out any anisotropic aspects. The importance of specifying the thermal
      characteristics of the sapwood according to axial, tangential or radial direction
      is revealed as well as referring to and using the proper anisotropic theory in
      order to avoid confusion and misinterpretation of thermal properties when dealing
      with sap flux density measurements or erroneous results when modelling heat
      transport in sapwood.

PMID- 22407650
TI  - Ammonium-induced loss of root gravitropism is related to auxin distribution and
      TRH1 function, and is uncoupled from the inhibition of root elongation in
      Arabidopsis.
AB  - Root gravitropism is affected by many environmental stresses, including salinity,
      drought, and nutrient deficiency. One significant environmental stress, excess
      ammonium (NH(4)(+)), is well documented to inhibit root elongation and lateral
      root formation, yet little is known about its effects on the direction of root
      growth. We show here that inhibition of root elongation upon elevation of
      external NH(4)(+) is accompanied by a loss in root gravitropism (agravitropism)
      in Arabidopsis. Addition of potassium (K(+)) to the treatment medium partially
      rescued the inhibition of root elongation by high NH(4)(+) but did not improve
      gravitropic root curvature. Expression analysis of the auxin-responsive reporter
      gene DR5::GUS revealed that NH(4)(+) treatment delayed the development of gravity
      induced auxin gradients across the root cap but extended their duration once
      initiated. Moreover, the beta-glucuronidase (GUS) signal intensity in root tip
      cells was significantly reduced under high NH(4)(+) treatment over time. The
      potassium carrier mutant trh1 displayed different patterns of root gravitropism
      and DR5::GUS signal intensity in root apex cells compared with the wild type in
      response to NH(4)(+). Together, the results demonstrate that the effects of
      NH(4)(+) on root gravitropism are related to delayed lateral auxin redistribution
      and the TRH1 pathway, and are largely independent of inhibitory effects on root
      elongation.

PMID- 22407649
TI  - Local and systemic mycorrhiza-induced protection against the ectoparasitic
      nematode Xiphinema index involves priming of defence gene responses in grapevine.
AB  - The ectoparasitic dagger nematode (Xiphinema index), vector of Grapevine fanleaf
      virus (GFLV), provokes gall formation and can cause severe damage to the root
      system of grapevines. Mycorrhiza formation by Glomus (syn. Rhizophagus)
      intraradices BEG141 reduced both gall formation on roots of the grapevine
      rootstock SO4 (Vitis berlandieri*V. riparia) and nematode number in the
      surrounding soil. Suppressive effects increased with time and were greater when
      the nematode was post-inoculated rather than co-inoculated with the arbuscular
      mycorrhizal (AM) fungus. Using a split-root system, decreased X. index
      development was shown in mycorrhizal and non-mycorrhizal parts of mycorrhizal
      root systems, indicating that both local and systemic induced bioprotection
      mechanisms were active against the ectoparasitic nematode. Expression analyses of
      ESTs (expressed sequence tags) generated in an SSH (subtractive suppressive
      hybridization) library, representing plant genes up-regulated during mycorrhiza
      induced control of X. index, and of described grapevine defence genes showed
      activation of chitinase 1b, pathogenesis-related 10, glutathione S-transferase,
      stilbene synthase 1, 5-enolpyruvyl shikimate-3-phosphate synthase, and a heat
      shock proein 70-interacting protein in association with the observed local and/or
      systemic induced bioprotection against the nematode. Overall, the data suggest
      priming of grapevine defence responses by the AM fungus and transmission of a
      plant-mediated signal to non-mycorrhizal tissues. Grapevine gene responses during
      AM-induced local and systemic bioprotection against X. index point to biological
      processes that are related either to direct effects on the nematode or to
      protection against nematode-imposed stress to maintain root tissue integrity.

PMID- 22407652
TI  - Mn(II) -Gd(III) phosphonate cages with a large magnetocaloric effect.

PMID- 22407651
TI  - Nutrition and asthma.
AB  - Over the past four decades, the prevalence of asthma has markedly increased in
      Westernized countries and countries transitioning to this lifestyle. It has been
      hypothesized that these increases are a consequence of changing environmental
      and/or behavioral factors. The modification of dietary habits (ie, decreased
      intake of fruits/vegetables and increased intake of "Westernized" processed
      foods) and a decrease in sun exposure have led to decreased intake of antioxidant
      vitamins and fatty acids and to decreased circulating levels of vitamin D, and
      have been proposed to explain the rise in asthma prevalence. This article
      summarizes the main findings on foods and nutrients connected to asthma based on
      several exhaustive recent reviews on the topic, and examines the evidence for an
      effect of dietary patterns on asthma. Overall, findings underscore the importance
      of conducting prospective studies and clinical trials to better understand the
      role of diet in the etiology of asthma.

PMID- 22407653
TI  - Acaricidal activities of Santolina africana and Hertia cheirifolia essential oils
      against the two-spotted spider mite (Tetranychus urticae).
AB  - BACKGROUND: Many plant essential oils show a broad spectrum of activity against
      pests. This study investigated the effects of two essential oils on Tetranychus
      urticae, one of the most serious pests in the world. RESULTS: The chemical
      composition of the two oils was characterised by GC-MS. The most abundant
      component in the Santolina africana (Jord. & Fourr) oil was terpinen-4-ol
      (54.96%), while thymol (61%) was prevalent in the Hertia cheirifolia (L.) oil.
      Mortality and fecundity were measured upon treatment with oil concentrations
      ranging from 0.07 to 6.75 mg L(-1) with a Potter spray tower. Mite mortality
      increased with oil concentration, with LC(50) values of 2.35 mg L(-1) for S.
      africana and 3.43 mg L(-1) for H. cheirifolia respectively. For both oils, a
      reduction in fecundity was observed at concentrations of 0.07, 0.09 and 0.29 mg
      L(-1) . Artificial blends of constituents of oils were also prepared and tested
      with individual constituents missing from the mixture. The results showed that
      the presence of all constituents was necessary to equal the toxicity of the two
      natural oils. CONCLUSION: S. africana and H. cheirifolia oils can provide
      valuable acaricide activity with significantly lower LC(50) values. Thus, these
      oils cause important mortality and reduce the number of eggs laid by females.

PMID- 22407654
TI  - Prognosis of cerebral vein thrombosis presenting as isolated headache: early vs.
      late diagnosis.
AB  - OBJECTIVE: To analyse the outcome of cerebral venous thrombosis (CVT) patients
      presenting with isolated headache, specifically to compare isolated headache
      patients with early vs. late CVT diagnosis. METHOD: In the International Study on
      Cerebral Vein and Dural Sinus Thrombosis (ISCVT) database we compared the outcome
      of patients with isolated headache and a CVT diagnosed early (<=7 days from
      onset) vs. late (>7 days). We retrieved 100 patients with isolated headache, 52
      patients with early CVT diagnosis (early isolated headache) and 48 with late CVT
      diagnosis (late isolated headache). RESULTS: Neurological worsening was more
      frequent within early isolated headache patients (23% vs. 8%) (p = 0.045). At the
      last follow-up (median 411 days), 93% patients had a complete recovery, and 4%
      were dead or dependent, with no significant difference between early isolated
      headache and late isolated headache. CONCLUSION: The outcome of CVT patients with
      isolated headache diagnosed early or late was similarly favourable, but there was
      a higher proportion of neurological worsening in the acute phase among early
      isolated headache patients, who need close neurological monitoring.

PMID- 22407655
TI  - Osmophobia as an early marker of migraine: a follow-up study in juvenile
      patients.
AB  - BACKGROUND: Osmophobia is frequent in children with migraine (20-35%) but can
      also occur in up to 14% of cases with tension-type headache (TTH). So far, the
      prognostic role of this symptom in children with primary headaches has never been
      evaluated. METHODS: A longitudinal prospective study was conducted on 90 young
      patients with TTH (37 with osmophobia, 53 without osmophobia). We evaluated
      whether osmophobia could predict the diagnosis transformation from TTH to
      migraine after a 3-year follow-up. RESULTS AND DISCUSSION: In our cases the rate
      of diagnosis change was significantly greater in cases with osmophobia (62%) than
      in those without (23%). Osmophobia persisted at a 3-year follow-up in the
      majority of our cases (85%) and it was found to be one of the major predictors
      for the development of migraine; other predictors of evolution to migraine were
      phonophobia, a probable rather than certain diagnosis of TTH and olfactory
      triggers (p < 0.05). CONCLUSION: Our data confirm that osmophobia has an
      important diagnostic and prognostic role in children with primary headaches and
      should be systematically investigated at diagnosis and during follow-up.

PMID- 22407656
TI  - Cluster headache and sleep, is there a connection? A review.
AB  - PURPOSE OF REVIEW: Sleep and the chronobiological disease cluster headache are
      believed to be interconnected. Despite efforts, the precise nature of the
      relationship remains obscured. A better understanding of this relation may lead
      to more effective therapeutic regimes for patients suffering from this
      debilitating disease. This review aims to evaluate the existing literature on the
      subject of cluster headache and sleep. LATEST FINDINGS: Several previous studies
      describe an association between episodic cluster headache and distinct
      macrostructural sleep phases. This association was not confirmed in a recent
      study of seven episodic cluster headache patients, but it was suggested that
      further studies into the correlation between cluster headache attacks and the
      microstructure of sleep are relevant. The connection between cluster headache and
      the hypocretins is currently under investigation. SUMMARY: There is evidence in
      favour of an association between episodic cluster headache and REM sleep whereas
      no such relation to chronic cluster headache has been reported. Particular
      features in the microstructure of sleep and arousal mechanisms could play a role
      in the pathogenesis of cluster headache. Reports indicate that cluster headache
      and obstructive sleep apnoea are associated. Single cases show improvement upon
      treatment of sleep apnoea, but the causal relationship remains in question.

PMID- 22407657
TI  - Migraine and erectile dysfunction: evidence from a population-based case-control
      study.
AB  - BACKGROUND: This case-control study aimed to estimate the association between
      erectile dysfunction (ED) and migraines using a nationwide population-based
      database in Taiwan. METHODS: The data used for this matched case-control study
      were retrieved from the Taiwan Longitudinal Health Insurance Database 2000. We
      identified 5763 patients with ED as the cases and randomly selected 17,289
      patients as the controls. Conditional logistic regression was used to calculate
      the odds ratios (OR) for prior migraine between cases and controls. RESULTS:
      After adjusting for hypertension, diabetes, hyperlipidaemia, renal disease,
      coronary heart disease, obesity, and alcohol abuse/alcohol dependence syndrome,
      conditional logistic regression revealed that among ED patients the odds of
      having been previously diagnosed with migraines was 1.63 (95% CI, 1.39-1.91) that
      of the control group. This risk was more pronounced in younger groups, with the
      highest risk being detected among those aged between 30 and 39 years. After
      adjusting for the above mentioned comorbidities, ED patients aged between 30 and
      39 years were found to be at 1.98 (95% CI, 1.67-2.23) times the risk of controls
      for having been previously diagnosed with migraines. CONCLUSION: We conclude that
      ED is associated with having been previously diagnosed with migraines,
      particularly in younger populations.

PMID- 22407658
TI  - Psychiatric comorbidity and response to preventative therapy in the treatment of
      severe migraine trial.
AB  - INTRODUCTION: Mood and anxiety disorders are comorbid with migraine and commonly
      assumed to portend a poor response to preventive migraine therapies. However,
      there is little evidence to support this assumption. METHOD: We examined impact
      of a mood and/or anxiety disorder diagnosis using American Psychiatric
      Association Diagnostic and Statistical Manual criteria on response to the three
      preventative migraine therapies evaluated in the Treatment of Severe Migraine
      trial (n = 177): beta-blocker, behavioral migraine management, or behavioral
      migraine management +beta-blocker. Daily diaries assessed migraine activity for
      the 16 months of the trial. The Migraine Specific Quality of Life Questionnaire
      and Headache Disability Inventory assessed headache-related disability at regular
      intervals. Mixed models for repeated measures examined changes in these three
      outcomes with preventative migraine therapy in participants with and without a
      mood or anxiety disorder diagnosis. RESULTS: Participants with a comorbid mood or
      anxiety disorder diagnosis recorded larger reductions in migraine days (p < .05)
      and larger reductions in the Migraine Specific Quality of Life Questionnaire (p <
      .001) and Headache Disability Inventory (p < .01) than did participants with
      neither diagnosis. DISCUSSION: Significantly larger reductions in migraine
      activity and migraine-related disability were observed in participants with a
      mood and/or anxiety disorder diagnosis than in participants who did not receive
      either diagnosis.

PMID- 22407660
TI  - Primary continuous unilateral headaches: a nosologic model for hemicrania
      continua.
AB  - BACKGROUND: Hemicrania continua was originally described as a strictly
      unilateral, continuous headache with an absolute response to indomethacin.
      Recognition of an increasing number of patients with the same clinical features
      except for a lack of response to indomethacin has generated controversy about
      whether the responsive/non-responsive phenotypes belong to the same disorder.
      DISCUSSION: We suggest that the non-responsive phenotype should be differentiated
      from the original concept of hemicrania continua, because it probably indicates a
      separate type of headache of undetermined nature, i.e. hemicrania incerta.
      However, differentiating hemicrania incerta from hemicrania continua does not
      imply that the two headaches are unrelated. Both hemicranias may outline a
      continuum, giving rise to a broader diagnostic field. CONCLUSION: There seems to
      be a syndrome of 'primary continuous unilateral headache' with at least two
      distinctive categories: hemicrania continua and hemicrania incerta, which are
      differentiated by their respective response to indomethacin. This division means
      plurality but adds precision, and allows a clear-cut diagnosis of some
      controversial cases.

PMID- 22407661
TI  - Spreading depolarizations in a case of migraine-related stroke.
AB  - BACKGROUND: Cortical spreading depolarization (CSD) has been implicated in the
      pathophysiology of migraine with aura. Patients that suffer from this type of
      migraine have shown a higher risk of developing an ischaemic stroke. CASE: A 42
      year-old female exhibited reoccurring migraine attacks for the first time 1 month
      before suffering an ischaemic infarction. Imaging studies revealed an occlusion
      in the right middle cerebral artery. Other possible disorders were excluded. It
      was possible to register 20 CSDs, of which 12 coincided with high levels of
      glutamate and lactate/pyruvate ratio. Loss of electrocorticographic activity was
      observed for 89 hours after the 8th depolarization. CONCLUSIONS: Migraine with
      aura symptoms may be induced by CSDs triggered by hypoperfusion states. Our case
      supports the idea of the migraine with aura-stroke continuum.

PMID- 22407662
TI  - Facial pain, scotomas and hemihypaesthesia as presenting symptoms of type A
      aortic dissection in a patient with migraine with aura.
AB  - We report the case of a 31-year-old man with a history of migraine with aura who
      was admitted to our emergency department because of a sudden onset of severe
      bilateral facial pain radiating bilaterally into the medial cervical region after
      defecation. The pain was accompanied by scotomas in the right visual field and
      hypaesthesia in both upper limbs. Imaging of the aorta and supra-aortic vessels
      revealed a type A aortic dissection. Subsequently, the patient received an aortic
      valve replacement and an aortic tube graft. After the surgery he experienced
      recurring visual disturbances with a sudden onset mimicking his migraine aura.
      Due to a new onset of atrial fibrillation, he was put on oral anticoagulants. At
      follow-up after 10 months he still reported episodic and mostly isolated visual
      auras with a gradual onset.

PMID- 22407664
TI  - Bone marrow donation perceptions among healthcare workers: a survey at University
      of Toledo Medical Center.

PMID- 22407663
TI  - A pilot study of yogic meditation for family dementia caregivers with depressive
      symptoms: effects on mental health, cognition, and telomerase activity.
AB  - BACKGROUND: This study examined the effects of brief daily yogic meditation on
      mental health, cognitive functioning, and immune cell telomerase activity in
      family dementia caregivers with mild depressive symptoms. METHODS: Thirty-nine
      family dementia caregivers (mean age 60.3 years old (SD = 10.2)) were randomized
      to practicing Kirtan Kriya or listening to relaxation music for 12 min per day
      for 8 weeks. The severity of depressive symptoms, mental and cognitive
      functioning were assessed at baseline and follow-up. Telomerase activity in
      peripheral blood mononuclear cells (PMBC) was examined in peripheral PBMC pre
      intervention and post-intervention. RESULTS: The meditation group showed
      significantly lower levels of depressive symptoms and greater improvement in
      mental health and cognitive functioning compared with the relaxation group. In
      the meditation group, 65.2% showed 50% improvement on the Hamilton Depression
      Rating scale and 52% of the participants showed 50% improvement on the Mental
      Health Composite Summary score of the Short Form-36 scale compared with 31.2% and
      19%, respectively, in the relaxation group (p < 0.05). The meditation group
      showed 43% improvement in telomerase activity compared with 3.7% in the
      relaxation group (p = 0.05). CONCLUSION: This pilot study found that brief daily
      meditation practices by family dementia caregivers can lead to improved mental
      and cognitive functioning and lower levels of depressive symptoms. This
      improvement is accompanied by an increase in telomerase activity suggesting
      improvement in stress-induced cellular aging. These results need to be confirmed
      in a larger sample.

PMID- 22407666
TI  - Hepatic arterial reconstruction with a short-term patency by using micro T-tube
      in rat liver transplantation.

PMID- 22407667
TI  - Efficient copper(II)-catalyzed transamidation of non-activated primary
      carboxamides and ureas with amines.
AB  - Amid(e) them all: primary carboxamides and ureas react with aromatic and
      aliphatic amines in the presence of a copper catalyst to give a wide range of
      functionalized amides.

PMID- 22407668
TI  - Pure dysgerminoma of the ovary: a single institutional experience of 65 patients.
AB  - Ovarian dysgerminomas are rare entity and account for only about 2% of all
      malignant ovarian neoplasm. The aim of this study was to evaluate the
      clinicopathologic characteristics, treatment, long-term survival, and fertility
      outcome of women diagnosed with ovarian dysgerminoma at our institution. Sixty
      five women with histologically proven pure ovarian dysgerminoma were identified
      in this retrospective study. They were treated at King Faisal Specialist
      Hospital, Riyadh; Saudi Arabia between 1976 and 2010. The median age was 20
      years. The most frequent symptoms at presentation were abdominal pain and
      abdominal/pelvic mass. Thirty-three patients (50.7%) presented with stage I, 2
      (3.1%) had stage II, 22 (33.8%) had stage III, and 4 (6.2%) had stage IV (4
      unknown stage). Unilateral oophorectomy was performed in 50 patients (76.9%)
      while bilateral oophorectomy+/-hysterectomy was done in 12 patients (18.4%).
      Three patients had biopsy only. Forty patients (61.5%) received only
      chemotherapy, and 4 patients (6.2%) received radiotherapy alone. Recurrence was
      observed in 6 patients (9.2%). With median follow-up of 54 months, the 5-year
      disease-free survival (DFS) and overall survival (OS) were 88 and 95%,
      respectively. On univariate analysis, adjuvant chemotherapy was independent
      better prognostic factor for DFS (HR, 0.09; 95% CI, 0.01-0.84; P=0.034). Of the
      50 patients treated with fertility-sparing surgery, 16 patients (32%) achieved
      pregnancy with 14 live births. Patients with pure ovarian dysgerminoma have
      excellent long-term outcome. There is no difference at outcome between fertility
      sparing and nonconservative surgeries. Adjuvant chemotherapy was associated with
      significant improvement in DFS. It is possible to maintain good reproductive
      function after conservative surgery followed by chemotherapy in our series.

PMID- 22407669
TI  - Should procalcitonin be used as a routine biomarker of bacterial infection?

PMID- 22407671
TI  - Chelation ability of spironaphthoxazine with metal ions in silica gel.
AB  - Spironaphthoxazine (SNO) and three metal ions, Mg(2+), Zn(2+), and Al(3+), were
      dispersed in silica gels by the sol-gel method. The chelation ability of SNO with
      the metal ions in silica gels was investigated by measuring the fluorescence
      spectra and was compared to that of 8-hydroxyquinoline (8-HQ) in ethanol and
      silica gels. A merocyanine-type isomer photoderived from SNO as well as 8-HQ
      easily formed complexes of the metal ions in the order of Al(3+), Zn(2+), and
      Mg(2+) because the coordination ability of the metal ions to such ligands
      depended on their electron affinity. The changes in the fluorescence spectra of
      the silica gel samples during light irradiation were also investigated. The
      relative band intensity due to the intermediate species between the original SNO
      and the merocyanine species decreased and that of the complex increased with the
      UV irradiation time. The reverse process was observed during visible irradiation.
      The UV irradiation effects on the chelation of SNO and its photochromic property
      also depended on the electron affinity of the metal ions.

PMID- 22407673
TI  - Probing the electronic structure and photoactivation process of nitrogen-doped
      TiO2 using DRS, PL, and EPR.
AB  - The electronic structure and photoactivation process in N-doped TiO(2) is
      investigated. Diffuse reflectance spectroscopy (DRS), photoluminescence (PL), and
      electron paramagnetic resonance (EPR) are employed to monitor the change of
      optical absorption ability and the formation of N species and defects in the heat
      and photoinduced N-doped TiO(2) catalyst. Under thermal treatment below 573 K in
      vacuum, no nitrogen dopant is removed from the doped samples but oxygen vacancies
      and Ti(3+) states are formed to enhance the optical absorption in the visible
      light region, especially at wavelengths above 500 nm with increasing temperature.
      In the photoactivation processes of N-doped TiO(2), the DRS absorption and PL
      emission in the visible spectral region of 450-700 nm increase with prolonged
      irradiation time. The EPR results reveal that paramagnetic nitrogen species
      (N(s)., oxygen vacancies with one electron (V(o).), and Ti(3+) ions are produced
      with light irradiation and the intensity of N(s). species is dependent on the
      excitation light wavelength and power. The combined characterization results
      confirm that the energy level of doped N species is localized above the valence
      band of TiO(2) corresponding to the main absorption band at 410 nm of N-doped
      TiO(2), but oxygen vacancies and Ti(3+) states as defects contribute to the
      visible-light absorption above 500 nm in the overall absorption of the doped
      samples. Thus, a detailed picture of the electronic structure of N-doped TiO(2)
      is proposed and discussed. On the other hand, the transfer of charge carriers
      between nitrogen species and defects is reversible on the catalyst surface. The
      presence of oxygen-vacancy-related defects leads to quenching of paramagnetic
      N(s). species but they stabilize the active nitrogen species N(s)(-).

PMID- 22407672
TI  - The risk of Guillain-Barre syndrome associated with influenza A (H1N1) 2009
      monovalent vaccine and 2009-2010 seasonal influenza vaccines: results from self
      controlled analyses.
AB  - PURPOSE: The Centers for Disease Control and Prevention Emerging Infections
      Program implemented active, population-based surveillance for Guillain-Barre
      syndrome (GBS) following H1N1 vaccines in 10 states/metropolitan areas. We report
      additional analyses of these data using self-controlled methods, which avoid
      potential confounding from person-level factors and co-morbidities. METHODS:
      Surveillance officers identified GBS cases with symptom onset during October 2009
      April 2010 and ascertained receipt of H1N1 vaccines. We calculated self
      controlled relative risks by comparing the number of cases with onset during a
      risk interval 1-42 days after vaccination with cases with onset during fixed
      (days 43-84) or variable (days 43-end of study period) control intervals. We
      calculated attributable risks by applying statistically significant relative
      risks to an independent estimate of GBS incidence. RESULTS: Fifty-nine GBS cases
      received H1N1 vaccine with or without seasonal vaccine. The relative risk was 2.1
      (95%CI 1.2, 3.5) by the variable-window and 3.0 (95%CI 1.4, 6.4) by the fixed
      window analyses. The corresponding attributable risks per million doses
      administered were 1.5 (95%CI 0.3, 3.4) and 2.8 (95%CI 0.6, 7.4). CONCLUSIONS:
      These attributable risks are similar to those of some previous formulations of
      seasonal influenza vaccine (about one to two cases per million doses
      administered), suggesting a low risk of GBS following the H1N1 vaccine that is
      not clearly higher than that of seasonal influenza vaccines.

PMID- 22407670
TI  - Human immunodeficiency virus protease inhibitors modulate Ca2+ homeostasis and
      potentiate alcoholic stress and injury in mice and primary mouse and human
      hepatocytes.
AB  - A portion of human immunodeficiency virus (HIV)-infected patients undergoing
      protease inhibitor (PI) therapy concomitantly consume or abuse alcohol leading to
      hepatic injury. The underling mechanisms are not known. We hypothesize that HIV
      PIs aggravate alcohol-induced liver injury through an endoplasmic reticulum (ER)
      stress mechanism. To address this, we treated mice, primary mouse hepatocytes
      (PMHs), and primary human hepatocytes (PHHs) with alcohol and the HIV PIs
      ritonavir (RIT) and lopinavir (LOP). In mice, RIT and LOP induced mild ER stress
      and inhibition of sarco/ER calcium-ATPase (SERCA) without significant increase in
      serum alanine aminotransferase (ALT) levels. However, a single dose of alcohol
      plus the two HIV PIs caused a more than five-fold increase in serum ALT, a
      synergistic increase in alcohol-induced liver lipid accumulation and ER stress
      response, and a decrease of SERCA. Mice treated with chronic HIV PIs and alcohol
      developed moderate liver fibrosis. In PMHs, the HIV drugs plus alcohol also
      inhibited SERCA expression and increased expression of glucose-regulated protein
      78, C/EBP homologous protein, sterol regulatory element-binding protein 1c, and
      phosphorylated c-Jun N-terminal kinase 2, which were accompanied by a synergistic
      increase in cell death compared with alcohol or the HIV drugs alone. In PHHs,
      treatment with RIT and LOP or alcohol alone increased messenger RNA of spliced X
      box-binding protein 1 and decreased SERCA, which were accompanied by reduced
      levels of intracellular calcium. Alcohol combined with the HIV drugs
      significantly reduced intracellular calcium levels and potentiated cell death,
      which was comparable to the cell death caused by the SERCA inhibitor
      thapsigargin. CONCLUSION: Our findings suggest the possibility that HIV PIs
      potentiate alcohol-induced ER stress and injury through modulation of SERCA and
      maintaining calcium homeostasis could be a therapeutic aim for better care of HIV
      patients.

PMID- 22407674
TI  - Sleep rounds: a multidisciplinary approach to optimize sleep quality and
      satisfaction in hospitalized patients.
AB  - BACKGROUND: Poor sleep has adverse affects on heath, yet few studies have
      addressed the goal of improving sleep among hospitalized patients. We evaluated
      the effectiveness of a sleep-promoting intervention on the quality and quantity
      of sleep among inpatients. METHODS: This study was conducted on a neurological
      ward in a large, tertiary care hospital. Sleep quality, quantity, and disruptors
      were assessed using questionnaires completed by patients during their hospital
      stay and Press Ganey surveys completed retrospectively. Room noise was also
      measured using noise meters. Data from each of 4 chronological phases of the
      study (baseline, basic intervention, "washout," and deluxe intervention) were
      analyzed. In the intervention phases, nurses conducted "Sleep Rounds" at bedtime,
      during which sleep-promoting practices were implemented, including lights out,
      television off, temperature adjustment, and a final restroom usage. RESULTS:
      Patients reported 5 (interquartile range [IQR] 3) hours of sleep per night, awoke
      3 (IQR 3) times nightly, and reported a median sleep latency of 11 to 15 minutes.
      Pain, staff interruptions, and roommates were the most significant barriers to
      good sleep. Noise levels were adequately low (35-40 dB) at night but were not
      positively impacted by our sleep-promoting interventions. Patients perceived
      noise on the unit to be worse during phases of the study in which there was no
      intervention. CONCLUSIONS: Patient perception of sleep experience improved during
      the phases in which Sleep Rounds were implemented, despite the fact that there
      was no measurable improvement in sleep or sleep-disrupting factors.

PMID- 22407675
TI  - A MID1 gene mutation in a patient with Opitz G/BBB syndrome that altered the 3D
      structure of SPRY domain.
AB  - Mutations in the MID1 gene result in X-linked Opitz G/BBB syndrome (OS), a
      disorder that affects development of midline structures and comprises
      hypertelorism, cleft lip/palate, hypospadias, and laryngo-tracheo-esophageal
      abnormalities, and, at times, neurological, anal, and cardiac defects. MID1 gene
      abnormalities include missense, nonsense, and splicing mutations, small
      insertions, small deletions, and complex rearrangements. Here, we present a
      patient with Opitz G/BBB syndrome and a unique MID1 gene point mutation c.1703T<C
      (p. Ile568Thr) in exon 10. This mutation was located in the loop between beta5
      and beta6 beta pleated sheets in the SPRY domain. According to our 3D models
      based on the PRY-SPRY domain of the human TRIM72, the I568T mutation altered the
      conformation in the loops between beta5 and beta6 and between beta7 and beta8.
      Thus, the I568T mutation altered the conformation of surface B of the binding
      pocket and may affect the binding affinity to the PRY domain.

PMID- 22407676
TI  - Development and application of endothelium-targeted microparticles for molecular
      magnetic resonance imaging.
AB  - Molecular imaging of disease states can enhance diagnosis allowing for accurate
      and more effective treatment. By specifically targeting molecules differentially
      expressed in disease states, researchers and clinicians have a means of disease
      characterization at a cellular or tissue level. Targeted micron-sized particles
      of iron oxide (MPIO) have been used as molecule-specific contrast agents for use
      with magnetic resonance imaging (MRI), and early evidence suggests they may be
      suitable for use with other imaging modalities. Targeting of MPIO to markers of
      disease is commonly achieved through the covalent attachment of antibodies to the
      surface of the particles, providing an imaging agent that is both highly specific
      and which binds with high affinity. When comparing micron-sized particles with
      nanometre-sized particles, the former provide substantial signal dropout in MRI
      and confer the sensitivity to detect low levels of target. Furthermore, larger
      particles appear to bind to targets more potently than smaller particles. Animal
      models have also demonstrated favorable blood clearance characteristics of MPIO,
      which are important in achieving favorable signal over background and to attain
      clearance and disposal. Although the current generation of commercially available
      MPIO are not suitable for administration into humans, future work may focus on
      the development of biodegradable and nonimmunogenic MPIO that may allow the use
      of these imaging agents in a clinical setting.

PMID- 22407677
TI  - Cucurbituril-modulated supramolecular assemblies: from cyclic oligomers to linear
      polymers.
AB  - Employing bis(p-sulfonatocalix[4]arenes) (bisSC4A) and N',N''hexamethylenebis(1
      methyl-4,4'-bipyridinium) (HBV(4+)) as monomer building blocks, the assembly
      morphologies can be modulated by cucurbit[n]uril (CB[n]) (n = 7, 8), achieving
      the interesting topological conversion from cyclic oligomers to linear polymers.
      The binary supramolecular assembly fabricated by HBV(4+) and bisSC4A units, forms
      an oligomeric structure, which was characterized by NMR spectroscopy, atomic
      force microscopy (AFM), transmission electron microscopy (TEM), dynamic light
      scattering (DLS), isothermal titration calorimetry (ITC), and gel permeation
      chromatography (GPC) experiments. The ternary supramolecular polymer participated
      by CB[8] is constructed on the basis of host-guest interactions by bisSC4A and
      the [2]pseudorotaxane HBV(4+)@CB[8], which is characterized by means of AFM, DLS,
      NMR spectroscopy, thermogravimetric analysis (TGA), UV/Vis spectroscopy, and
      elemental analysis. CB[n] plays vital roles in rigidifying the conformation of
      HBV(4+), and reinforcing the host-guest inclusion of bisSC4A with HBV(4+), which
      prompts the formation of a linear polymer. Moreover, the CB[8]-participated
      ternary assembly could disassemble into the molecular loop HBV(2+)@CB[8] and free
      bisSC4A after reduction of HBV(4+) to HBV(2+), whereas the CB[7]-based assembly
      remained unchanged after the reduction. CB[8] not only controlled the topological
      conversion of the supramolecular assemblies, but also improved the redox
      responsive assembly/disassembly property practically.

PMID- 22407678
TI  - Imaging in gynecological disease (7): clinical and ultrasound features of Brenner
      tumors of the ovary.
AB  - OBJECTIVES: To describe clinical and ultrasound features of Brenner tumors of the
      ovary. METHODS: In this retrospective study, the databases of the International
      Ovarian Tumor Analysis (IOTA) studies and one tertiary center were searched to
      identify patients who had undergone an ultrasound scan before surgery for an
      adnexal mass that proved to be a Brenner tumor. Twenty-eight patients with 29
      Brenner tumors were included, most of which had been collected within the
      framework of the IOTA studies. An experienced ultrasound examiner reviewed
      available ultrasound images (available for 14 tumors), searching for a pattern
      specific to Brenner tumors. RESULTS: Most patients were postmenopausal and
      asymptomatic. Twenty-four (83%) tumors were benign, two (7%) were borderline and
      three (10%) were malignant. Most benign tumors (17/24, 71%) contained solid
      components and manifested no or minimal blood flow on Doppler examination (19/24,
      79%). Information about calcifications was available for 15 benign tumors, and in
      13 (87%) calcifications were present. The five borderline and invasively
      malignant tumors contained solid components less often than did the benign ones
      (3/5, 60%) and were more richly vascularized on Doppler examination. Information
      about calcifications was available for four borderline or invasively malignant
      tumors, and in three (75%) calcifications were present. CONCLUSION: We failed to
      demonstrate ultrasound features specific to Brenner tumors. A prospective study
      is needed to determine if ultrasound features of calcifications can discriminate
      between Brenner tumors and other types of ovarian tumor.

PMID- 22407679
TI  - Cloning, overexpression in Escherichia coli, and characterization of a
      thermostable fungal acetylxylan esterase from Talaromyces emersonii.
AB  - The gene encoding an acetylxylan esterase (AXE1) from the thermophilic ascomycete
      Talaromyces emersonii was cloned, expressed in Escherichia coli, and
      characterized. This form of AXE1, rTeAXE1, exhibits increased thermostability and
      activity at a higher temperature than other known fungal acetyl esterases, thus
      having huge potential application in biomass bioconversion to high value
      chemicals or biofuels.

PMID- 22407680
TI  - Isolation of potentially novel Brucella spp. from frogs.
AB  - Bacterial isolates from frogs were phenotypically identified as Ochrobactrum
      anthropi, but 16S rRNA sequencing showed up to 100% identity with Brucella
      inopinata. Further analysis of recA, omp2a, omp2b, bcsp31, and IS711 and
      multilocus sequence analysis (MLSA) verified a close relationship with Brucella,
      suggesting the isolates may actually represent novel members of this growing
      genus of zoonotic pathogens.

PMID- 22407681
TI  - Role of the lizard Teira dugesii as a potential host for Ixodes ricinus tick
      borne pathogens.
AB  - PCR screening of ticks and tissue samples collected from 151 Teira dugesii
      lizards seems to indicate a potential role of this lizard species in the
      maintenance and transmission cycle of some Ixodes ricinus tick-borne agents, such
      as Rickettsia monacensis, Rickettsia helvetica, and Borrelia lusitaniae, that are
      circulating on Madeira Island.

PMID- 22407682
TI  - Transcriptional response of the cellobiose dehydrogenase gene to cello- and
      xylooligosaccharides in the basidiomycete Phanerochaete chrysosporium.
AB  - Cellobiose dehydrogenase (CDH) gene transcripts were quantified by reverse
      transcription-PCR (RT-PCR) in cultures of Phanerochaete chrysosporium
      supplemented with various cello- and xylooligosaccharides in order to elucidate
      the mechanism of enhanced CDH production in xylan/cellulose culture. Cellotriose
      and cellotetraose induced cdh expression, while xylobiose and xylotriose induced
      expression of cellobiohydrolase genes, especially cel7C.

PMID- 22407683
TI  - Characterization of extended-spectrum beta-lactamase genes found among
      Escherichia coli isolates from duck and environmental samples obtained on a duck
      farm.
AB  - In this study, we focused on evaluating the occurrence of extended-spectrum beta
      lactamase (ESBL)-producing Escherichia coli in fecal samples of healthy ducks and
      environmental samples from a duck farm in South China. Duck cloacal swabs and
      pond water samples were cultivated on MacConkey agar plates supplemented with
      ceftiofur. Individual colonies were examined for ESBL production. Bacteria
      identified as E. coli were screened for the presence of ESBL and plasmid-borne
      AmpC genes. The genetic relatedness, plasmid replicon type, and genetic
      background were determined. Of 245 samples analyzed, 123 had E. coli isolates
      with ceftiofur MICs higher than 8 MUg/ml (116 [50.4%] from 230 duck samples and 7
      [46.7%] from 15 water samples). bla(CTX-M), bla(SHV-12), bla(CMY-2), and bla(DHA
      1) were identified in 108, 5, 9, and 1 isolates, respectively. The most common
      bla(CTX-M) genes were bla(CTX-M-27) (n = 34), bla(CTX-M-55) (n = 27), bla(CTX-M
      24e) (n = 22), and bla(CTX-M-105) (n = 20), followed by bla(CTX-M-14a), bla(CTX-M
      14b), bla(CTX-M-24a), and bla(CTX-M-24b). Although most of the CTX-M producers
      had distinct pulsotypes, clonal transmission between duck and water isolates was
      observed. bla(CTX-M) genes were carried by transferable IncN, IncF, and
      untypeable plasmids. The novel CTX-M gene bla(CTX-M-105) was flanked by two
      hypothetical protein sequences, partial ISEcp1 upstream and truncated IS903D,
      iroN, orf1, and a Tn1721-like element downstream. It is suggested that the
      horizontal transfer of bla(CTX-M) genes mediated by mobile elements and the
      clonal spread of CTX-M-producing E. coli isolates contributed to the
      dissemination of bla(CTX-M) in the duck farm. Our findings highlight the
      importance of ducks for the dissemination of transferable antibiotic resistance
      genes into the environment.

PMID- 22407684
TI  - Intraradical dynamics of two coexisting isolates of the arbuscular mycorrhizal
      fungus Glomus intraradices sensu lato as estimated by real-time PCR of
      mitochondrial DNA.
AB  - Real-time PCR in nuclear ribosomal DNA (nrDNA) is becoming a well-established
      tool for the quantification of arbuscular mycorrhizal (AM) fungi, but this
      genomic region does not allow the specific amplification of closely related
      genotypes. The large subunit of mitochondrial DNA (mtDNA) has a higher-resolution
      power, but mtDNA-based quantification has not been previously explored in AM
      fungi. We applied real-time PCR assays targeting the large subunit of mtDNA to
      monitor the DNA dynamics of two isolates of Glomus intraradices sensu lato
      coexisting in the roots of medic (Medicago sativa). The mtDNA-based
      quantification was compared to quantification in nrDNA. The ratio of copy numbers
      determined by the nrDNA- and mtDNA-based assays consistently differed between the
      two isolates. Within an isolate, copy numbers of the nuclear and the
      mitochondrial genes were closely correlated. The two quantification approaches
      revealed similar trends in the dynamics of both isolates, depending on whether
      they were inoculated alone or together. After 12 weeks of cultivation,
      competition between the two isolates was observed as a decrease in the mtDNA copy
      numbers of one of them. The coexistence of two closely related isolates, which
      cannot be discriminated by nrDNA-based assays, was thus identified as a factor
      influencing the dynamics of AM fungal DNA in roots. Taken together, the results
      of this study show that real-time PCR assays targeted to the large subunit of
      mtDNA may become useful tools for the study of coexisting AM fungi.

PMID- 22407685
TI  - Genetic analysis of the upper phenylacetate catabolic pathway in the production
      of tropodithietic acid by Phaeobacter gallaeciensis.
AB  - Production of the antibiotic tropodithietic acid (TDA) depends on the central
      phenylacetate catabolic pathway, specifically on the oxygenase PaaABCDE, which
      catalyzes epoxidation of phenylacetyl-coenzyme A (CoA). Our study was focused on
      genes of the upper part of this pathway leading to phenylacetyl-CoA as precursor
      for TDA. Phaeobacter gallaeciensis DSM 17395 encodes two genes with homology to
      phenylacetyl-CoA ligases (paaK1 and paaK2), which were shown to be essential for
      phenylacetate catabolism but not for TDA biosynthesis and phenylalanine
      degradation. Thus, in P. gallaeciensis another enzyme must produce phenylacetyl
      CoA from phenylalanine. Using random transposon insertion mutagenesis of a paaK1
      paaK2 double mutant we identified a gene (ior1) with similarity to iorA and iorB
      in archaea, encoding an indolepyruvate:ferredoxin oxidoreductase (IOR). The ior1
      mutant was unable to grow on phenylalanine, and production of TDA was
      significantly reduced compared to the wild-type level (60%). Nuclear magnetic
      resonance (NMR) spectroscopic investigations using (13)C-labeled phenylalanine
      isotopomers demonstrated that phenylalanine is transformed into phenylacetyl-CoA
      by Ior1. Using quantitative real-time PCR, we could show that expression of ior1
      depends on the adjacent regulator IorR. Growth on phenylalanine promotes
      production of TDA, induces expression of ior1 (27-fold) and paaK1 (61-fold), and
      regulates the production of TDA. Phylogenetic analysis showed that the aerobic
      type of IOR as found in many roseobacters is common within a number of different
      phylogenetic groups of aerobic bacteria such as Burkholderia, Cupriavidis, and
      Rhizobia, where it may also contribute to the degradation of phenylalanine.

PMID- 22407686
TI  - Influence of seasonality on the genetic diversity of Vibrio parahaemolyticus in
      New Hampshire shellfish waters as determined by multilocus sequence analysis.
AB  - Risk of gastric infection with Vibrio parahaemolyticus increases with favorable
      environmental conditions and population shifts that increase prevalence of
      infective strains. Genetic analysis of New Hampshire strains revealed a unique
      population with some isolates similar to outbreak-causing strains and high-level
      diversity that increased as waters warmed.

PMID- 22407687
TI  - Properties and biological role of streptococcal fratricins.
AB  - Competence for natural genetic transformation is widespread in the genus
      Streptococcus. The current view is that all streptococcal species possess this
      property. In addition to the proteins required for DNA uptake and recombination,
      competent streptococci secrete muralytic enzymes termed fratricins. Since the
      synthesis and secretion of these cell wall-degrading enzymes are always coupled
      to competence development in streptococci, fratricins are believed to carry out
      an important function associated with natural transformation. This minireview
      summarizes what is known about the properties of fratricins and discusses their
      possible biological roles in streptococcal transformation.

PMID- 22407689
TI  - Density of the waterborne parasite Ceratomyxa shasta and its biological effects
      on salmon.
AB  - The myxozoan parasite Ceratomyxa shasta is a significant pathogen of juvenile
      salmonids in the Pacific Northwest of North America and is limiting recovery of
      Chinook (Oncorhynchus tshawytscha) and coho (O. kisutch) salmon populations in
      the Klamath River. We conducted a 5-year monitoring program that comprised
      concurrent sentinel fish exposures and water sampling across 212 river kilometers
      of the Klamath River. We used percent mortality and degree-days to death to
      measure disease severity in fish. We analyzed water samples using quantitative
      PCR and Sanger sequencing, to determine total parasite density and relative
      abundance of C. shasta genotypes, which differ in their pathogenicity to
      salmonids. We detected the parasite throughout the study zone, but parasite
      density and genetic composition fluctuated spatially and temporally. Chinook and
      coho mortality increased with density of their specific parasite genotype, but
      mortality-density thresholds and time to death differed. A lethality threshold of
      40% mortality was reached with 10 spores liter(-1) for Chinook but only 5 spores
      liter(-1) for coho. Parasite density did not affect degree-days to death for
      Chinook but was negatively correlated for coho, and there was wider variation
      among coho individuals. These differences likely reflect the different life
      histories and genetic heterogeneity of the salmon populations. Direct
      quantification of the density of host-specific parasite genotypes in water
      samples offers a management tool for predicting host population-level impacts.

PMID- 22407690
TI  - Psychrotolerant Paenibacillus tundrae isolates from barley grains produce new
      cereulide-like depsipeptides (paenilide and homopaenilide) that are highly toxic
      to mammalian cells.
AB  - Paenilide is a novel, heat-stable peptide toxin from Paenibacillus tundrae, which
      colonizes barley. P. tundrae produced 20 to 50 ng of the toxin mg(-1) of cells
      (wet weight) throughout a range of growth temperatures from +5 degrees C to +28
      degrees C. Paenilide consisted of two substances of 1,152 Da and 1,166 Da, with
      masses and tandem mass spectra identical to those of cereulide and a cereulide
      homolog, respectively, produced by Bacillus cereus NS-58. The two components of
      paenilide were separated from those of cereulide by high-performance liquid
      chromatography (HPLC), showing a structural difference suggesting the replacement
      of O-Leu (cereulide) by O-Ile (paenilide). The exposure of porcine spermatozoa
      and kidney tubular epithelial (PK-15) cells to subnanomolar concentrations of
      paenilide resulted in inhibited motility, the depolarization of mitochondria,
      excessive glucose consumption, and metabolic acidosis. Paenilide was similar to
      cereulide in eight different toxicity endpoints with porcine and murine cells. In
      isolated rat liver mitochondria, nanomolar concentrations of paenilide collapsed
      respiratory control, zeroed the mitochondrial membrane potential, and induced
      swelling. The toxic effect of paenilide depended on its high lipophilicity and
      activity as a high-affinity potassium ion carrier. Similar to cereulide,
      paenilide formed lipocations, i.e., lipophilic cationic compounds, with K(+) ions
      already at 4 mM [K(+)], rendering lipid membranes electroconductive. Paenilide
      producing P. tundrae was negative in a PCR assay with primers specific for the
      cesB gene, indicating that paenilide was not a product of plasmid pCER270,
      encoding the biosynthesis of cereulide in B. cereus. Paenilide represents the
      first potassium ionophoric compound described for Paenibacillus. The findings in
      this paper indicate that paenilide from P. tundrae is a potential food-poisoning
      agent.

PMID- 22407691
TI  - Functional robustness of a polycyclic aromatic hydrocarbon metabolic network
      examined in a nidA aromatic ring-hydroxylating oxygenase mutant of Mycobacterium
      vanbaalenii PYR-1.
AB  - In this study, we obtained over 4,000 transposon mutants of Mycobacterium
      vanbaalenii PYR-1 and analyzed one of the mutants, 8F7, which appeared to lose
      its ability to degrade pyrene while still being able to degrade fluoranthene.
      This mutant was identified to be defective in nidA, encoding an aromatic ring
      hydroxylating oxygenase (RHO), known to be involved in the initial oxidation step
      of pyrene degradation. When cultured with pyrene as a sole source of polycyclic
      aromatic hydrocarbon (PAH), high-pressure liquid chromatography analysis revealed
      that the nidA mutant showed a significant decrease in the rate of pyrene
      degradation compared to the wild-type PYR-1, although pyrene was still being
      degraded. However, when incubated with PAH mixtures including pyrene,
      phenanthrene, and fluoranthene, the pyrene degradation rate of the mutant was
      higher than that of the mutant previously incubated with pyrene as a sole source
      of PAH. There was no significant difference between wild-type PYR-1 and the
      mutant in the rates of phenanthrene and fluoranthene degradation. From the whole
      cell proteome analysis of mutant 8F7 induced by pyrene, we identified expression
      of a number of RHO enzymes which are suspected to be responsible for pyrene
      degradation in the nidA mutant, which had no expression of NidA. Taken together,
      results in this study provide direct evidence for the in vivo functional role of
      nidA in pyrene degradation at the level of the ring-cleavage-process (RCP)
      functional module but also for the robustness of the PAH metabolic network (MN)
      to such a genetic perturbation.

PMID- 22407692
TI  - Characterization of the intracellular glutamate decarboxylase system: analysis of
      its function, transcription, and role in the acid resistance of various strains
      of Listeria monocytogenes.
AB  - The glutamate decarboxylase (GAD) system is important for the acid resistance of
      Listeria monocytogenes. We previously showed that under acidic conditions,
      glutamate (Glt)/gamma-aminobutyrate (GABA) antiport is impaired in minimal media
      but not in rich ones, like brain heart infusion. Here we demonstrate that this
      behavior is more complex and it is subject to strain and medium variation.
      Despite the impaired Glt/GABA antiport, cells accumulate intracellular GABA
      (GABA(i)) as a standard response against acid in any medium, and this occurs in
      all strains tested. Since these systems can occur independently of one another,
      we refer to them as the extracellular (GAD(e)) and intracellular (GAD(i))
      systems. We show here that GAD(i) contributes to acid resistance since in a
      DeltagadD1D2 mutant, reduced GABA(i) accumulation coincided with a 3.2-log-unit
      reduction in survival at pH 3.0 compared to that of wild-type strain LO28. Among
      20 different strains, the GAD(i) system was found to remove 23.11% +/- 18.87% of
      the protons removed by the overall GAD system. Furthermore, the GAD(i) system is
      activated at milder pH values (4.5 to 5.0) than the GAD(e) system (pH 4.0 to
      4.5), suggesting that GAD(i) is the more responsive of the two and the first line
      of defense against acid. Through functional genomics, we found a major role for
      GadD2 in the function of GAD(i), while that of GadD1 was minor. Furthermore, the
      transcription of the gad genes in three common reference strains (10403S, LO28,
      and EGD-e) during an acid challenge correlated well with their relative acid
      sensitivity. No transcriptional upregulation of the gadT2D2 operon, which is the
      most important component of the GAD system, was observed, while gadD3
      transcription was the highest among all gad genes in all strains. In this study,
      we present a revised model for the function of the GAD system and highlight the
      important role of GAD(i) in the acid resistance of L. monocytogenes.

PMID- 22407693
TI  - Metabolome and transcriptome of the interaction between Ustilago maydis and
      Fusarium verticillioides in vitro.
AB  - The metabolome and transcriptome of the maize-infecting fungi Ustilago maydis and
      Fusarium verticillioides were analyzed as the two fungi interact. Both fungi were
      grown for 7 days in liquid medium alone or together in order to study how this
      interaction changes their metabolomic and transcriptomic profiles. When grown
      together, decreased biomass accumulation occurs for both fungi after an initial
      acceleration of growth compared to the biomass changes that occur when grown
      alone. The biomass of U. maydis declined most severely over time and may be
      attributed to the action of F. verticillioides, which secretes toxic secondary
      metabolites and expresses genes encoding adhesive and cell wall-degrading
      proteins at higher levels than when grown alone. U. maydis responds to
      cocultivation by expressing siderophore biosynthetic genes and more highly
      expresses genes potentially involved in toxin biosynthesis. Also, higher
      expression was noted for clustered genes encoding secreted proteins that are
      unique to U. maydis and that may play a role during colonization of maize.
      Conversely, decreased gene expression was seen for U. maydis genes encoding the
      synthesis of ustilagic acid, mannosylerythritol D, and another uncharacterized
      metabolite. Ultimately, U. maydis is unable to react efficiently to the toxic
      response of F. verticillioides and proportionally loses more biomass. This in
      vitro study clarifies potential mechanisms of antagonism between these two fungi
      that also may occur in the soil or in maize, niches for both fungi where they
      likely interact in nature.

PMID- 22407694
TI  - A Pseudomonas viridiflava-related bacterium causes a dark-reddish spot disease in
      Glycine max.
AB  - A virulent Pseudomonas viridiflava-related bacterium has been identified as a new
      pathogen of soybean, one of the most important crops worldwide. The bacterium was
      recovered from forage soybean leaves with dark-reddish spots, and damage on
      petioles and pods was also observed. In contrast, common bean was not affected.

PMID- 22407688
TI  - Central role of dynamic tidal biofilms dominated by aerobic hydrocarbonoclastic
      bacteria and diatoms in the biodegradation of hydrocarbons in coastal mudflats.
AB  - Mudflats and salt marshes are habitats at the interface of aquatic and
      terrestrial systems that provide valuable services to ecosystems. Therefore, it
      is important to determine how catastrophic incidents, such as oil spills,
      influence the microbial communities in sediment that are pivotal to the function
      of the ecosystem and to identify the oil-degrading microbes that mitigate damage
      to the ecosystem. In this study, an oil spill was simulated by use of a tidal
      chamber containing intact diatom-dominated sediment cores from a temperate
      mudflat. Changes in the composition of bacteria and diatoms from both the
      sediment and tidal biofilms that had detached from the sediment surface were
      monitored as a function of hydrocarbon removal. The hydrocarbon concentration in
      the upper 1.5 cm of sediments decreased by 78% over 21 days, with at least 60%
      being attributed to biodegradation. Most phylotypes were minimally perturbed by
      the addition of oil, but at day 21, there was a 10-fold increase in the amount of
      cyanobacteria in the oiled sediment. Throughout the experiment, phylotypes
      associated with the aerobic degradation of hydrocarbons, including polycyclic
      aromatic hydrocarbons (PAHs) (Cycloclasticus) and alkanes (Alcanivorax,
      Oleibacter, and Oceanospirillales strain ME113), substantively increased in oiled
      mesocosms, collectively representing 2% of the pyrosequences in the oiled
      sediments at day 21. Tidal biofilms from oiled cores at day 22, however,
      consisted mostly of phylotypes related to Alcanivorax borkumensis (49% of
      clones), Oceanospirillales strain ME113 (11% of clones), and diatoms (14% of
      clones). Thus, aerobic hydrocarbon biodegradation is most likely to be the main
      mechanism of attenuation of crude oil in the early weeks of an oil spill, with
      tidal biofilms representing zones of high hydrocarbon-degrading activity.

PMID- 22407695
TI  - Radiofrequency ablation: technique and clinical applications.
AB  - Radiofrequency ablation is the most commonly used percutaneous ablation    
      technique and well-documented in the literature on focal therapies. It has    
      become the image-guided ablation method of choice because of its efficacy,    
      safety, and ease of use. Radiofrequency ablation has shown promise in treating   
      selected solid tumors, particularly those involving the liver, kidneys, lungs,  
      and the musculoskeletal system. It is a minimally invasive technique often used
      in inoperable patients with other comorbidities. Radiofrequency ablation    
      requires a minimal hospital stay or can be performed on an outpatient basis. The 
      aim of this article is to review radiofrequency ablation techniques and their 
      clinical applications.

PMID- 22407696
TI  - Imaging features of bone metastases in patients with gastrointestinal stromal
      tumors.
AB  - PURPOSE: To determine the prevalence and imaging features of bone metastases in
      patients with gastrointestinal stromal tumors (GISTs). MATERIALS AND METHODS: The
      medical records of 190 patients with pathologically proven GISTs were reviewed,
      and patients with bone metastases were identified. Computed tomography (CT) scans
      of the chest, abdomen, and pelvis were examined for features of bone metastases,
      and findings were correlated with the results of positron-emission tomography
      (PET) and histopathology. RESULTS: Of 190 GIST patients, six (3.2%) had bone
      metastases: four patients had multiple bone metastases, and two patients had a
      solitary metastasis. The maximum diameter of the metastases ranged from 2 to 40
      mm, and they most commonly involved the vertebrae, ribs, pelvic bones, and
      femurs. All lesions were well-marginated and lytic. A soft tissue component was
      identified in three patients. The bone metastases showed intense fluorine-18
      fluorodeoxyglucose (FDG) uptake. After treatment with imatinib mesylate in three
      patients, the bone metastases developed peripheral sclerosis on CT and became
      less FDG-avid on PET. All six primary tumors were morphologically high-grade with
      high mitotic rates and necrosis. CONCLUSION: Bone metastases from GISTs are
      uncommon; when detected with CT, they are characterized by single or multiple
      lytic lesions with or without soft tissue involvement. A sclerotic rim may appear
      around the metastatic lesions in response to treatment. Similar to the disease in
      other sites, bone metastases show intense FDG uptake, which decreases following
      treatment.

PMID- 22407697
TI  - A novel three-component [3+2] cycloannulation process for the rapid and highly
      stereoselective synthesis of pyrrolobenzoxazoles.

PMID- 22407698
TI  - Fertility awareness and parenting attitudes among American male and female
      undergraduate university students.
AB  - BACKGROUND: In the USA, the postponement of childbearing reflects contemporary
      social norms of delaying marriage, pursing educational goals and securing
      economic stability prior to attempting conception. Although university students
      are more likely to delay childbearing, it is unclear to what extent they are
      aware of age-related fertility decline. The current study is the first of its
      kind to assess fertility awareness and parenting attitudes of American
      undergraduate university students. METHODS: Two-hundred forty-six randomly
      selected undergraduate university students (138 females and 108 males) completed
      an online self-report survey adapted from the Swedish Fertility Awareness
      Questionnaire. Students were evenly distributed between the freshman, sophomore,
      junior and senior classes with a mean age of 20.4 years. RESULTS: Participants
      wanted to have their first and last child within the window of a woman's
      fertility. However, participants demonstrated a lack of fertility awareness by
      vastly overestimating the age at which women experience declines in fertility,
      the likelihood of pregnancy following unprotected intercourse and the chances
      that IVF treatments would be successful in the case of infertility. Nearly 9 in
      10 participants want to have children in the future and viewed parenthood as a
      highly important aspect of their future lives. CONCLUSIONS: Delaying childbearing
      based on incorrect perceptions of female fertility could lead to involuntary
      childlessness. Education regarding fertility issues is necessary to help men and
      women make informed reproductive decisions that are based on accurate information
      rather than incorrect perceptions.

PMID- 22407699
TI  - Resources and waste management in a bio-based economy.

PMID- 22407700
TI  - Comparative analysis of solid waste management in 20 cities.
AB  - This paper uses the 'lens' of integrated and sustainable waste management (ISWM)
      to analyse the new data set compiled on 20 cities in six continents for the UN
      Habitat flagship publication Solid Waste Management in the World's Cities. The
      comparative analysis looks first at waste generation rates and waste composition
      data. A process flow diagram is prepared for each city, as a powerful tool for
      representing the solid waste system as a whole in a comprehensive but concise
      way. Benchmark indicators are presented and compared for the three key physical
      components/drivers: public health and collection; environment and disposal; and
      resource recovery--and for three governance strategies required to deliver a well
      functioning ISWM system: inclusivity; financial sustainability; and sound
      institutions and pro-active policies. Key insights include the variety and
      diversity of successful models - there is no 'one size fits all'; the necessity
      of good, reliable data; the importance of focusing on governance as well as
      technology; and the need to build on the existing strengths of the city. An
      example of the latter is the critical role of the informal sector in the cities
      in many developing countries: it not only delivers recycling rates that are
      comparable with modern Western systems, but also saves the city authorities
      millions of dollars in avoided waste collection and disposal costs. This provides
      the opportunity for win-win solutions, so long as the related wider challenges
      can be addressed.

PMID- 22407704
TI  - Introduction to genome biology: features, processes, and structures.
AB  - Genomic analyses increasingly make use of sophisticated statistical and
      computational approaches in investigations of genomic function and evolution.
      Scientists implementing and developing these approaches are often computational
      scientists, physicists, or mathematicians. This article aims to provide a compact
      overview of genome biology for these scientists. Thus, the article focuses on
      providing biological context to the genomic features, processes, and structures
      analysed by these approaches. Topics covered include (1) differences between
      eukaryotic and prokaryotic cells; (2) the physical structure of genomes and
      chromatin; (3) different categories of genomic regions, including those serving
      as templates for RNA and protein synthesis, regulatory regions, repetitive
      regions, and "architectural" or "organisational" regions, such as centromeres and
      telomeres; (4) the cell cycle; (5) an overview of transcription, translation, and
      protein structure; and (6) a glossary of relevant terms.

PMID- 22407703
TI  - Pharmacokinetics of nilotinib in imatinib-resistant/intolerant chronic myeloid
      leukemia patients on hemodialysis for chronic renal failure.

PMID- 22407705
TI  - Diversity of genome organisation.
AB  - Genomes can be organised in different ways. Understanding the extent of the
      diversity of genome organisation, the processes that create it, and its
      consequences is particularly important for two key reasons. Firstly, it is
      relevant for our understanding of the genetic basis for the astounding diversity
      of life on Earth. Elucidating the mechanisms and processes underlying such
      diversity has been, and remains, one of the central goals of biological research.
      Secondly, it helps prepare us for our analysis of new genomes. For example,
      knowing that plasmids can be circular or linear, we know to check for circularity
      or linearity in a plasmid we encounter for the first time (if this is relevant
      for our analysis). This article provides an overview of variation and diversity
      in several aspects of genome organisation and architecture, including the number,
      size, ploidy, composition (RNA or DNA), packaging, and topology of the molecules
      encoding the genome. Additionally, it reviews differences in selected genomic
      features, i.e. telomeres, centromeres, DNA replication origins, and sex
      chromosomes. To put this in context, it incorporates a brief survey of organism
      diversity and the tree of life, and ends with a discussion of mutation mechanisms
      and inheritance, and explanations of key terms used to describe genomic
      variation.

PMID- 22407706
TI  - Probability, statistics, and computational science.
AB  - In this chapter, we review basic concepts from probability theory and
      computational statistics that are fundamental to evolutionary genomics. We
      provide a very basic introduction to statistical modeling and discuss general
      principles, including maximum likelihood and Bayesian inference. Markov chains,
      hidden Markov models, and Bayesian network models are introduced in more detail
      as they occur frequently and in many variations in genomics applications. In
      particular, we discuss efficient inference algorithms and methods for learning
      these models from partially observed data. Several simple examples are given
      throughout the text, some of which point to models that are discussed in more
      detail in subsequent chapters.

PMID- 22407707
TI  - The essentials of computational molecular evolution.
AB  - In this chapter, we give a brief yet self-contained introduction to computational
      molecular evolution. In particular, we present the emergence of the use of
      likelihood-based methods, review the standard DNA substitution models, and
      introduce how model choice operates. We also present recent developments in
      inferring absolute dates and rates on a phylogeny and show how state-of-the-art
      models take inspiration from diffusion theory to link population genetics, which
      traditionally focuses at a taxonomic level under that of species, and molecular
      evolution.

PMID- 22407708
TI  - Next-generation sequencing technologies and fragment assembly algorithms.
AB  - As a classic topic in bioinformatics, the fragment assembly problem has been
      studied for over two decades. Fragment assembly algorithms take a set of DNA
      fragments as input, piece them together into a set of aligned overlapping
      fragments (i.e., contigs), and output a consensus sequence for each of the
      contigs. The rapid advance of massively parallel sequencing, often referred to as
      next-generation sequencing (NGS) technologies, has revolutionized DNA sequencing
      by reducing both its time and cost by several orders of magnitude in the past few
      years, but posed new challenges for fragment assembly. As a result, many new
      approaches have been developed to assemble NGS sequences, which are typically
      shorter with a higher error rate, but at a much higher throughput, than classic
      methods provided. In this chapter, we review both classic and new algorithms for
      fragment assembly, with a focus on NGS sequences. We also discuss a few new
      assembly problems emerging from the broader applications of NGS techniques, which
      are distinct from the classic fragment assembly problem.

PMID- 22407709
TI  - Gene prediction.
AB  - Evolutionary genomics is a field that relies heavily upon comparing genomes, that
      is, the full complement of genes of one species with another. However, given a
      genome sequence and little else, as is now often the case, genes must first be
      found and annotated before downstream analyses can be done. Computational gene
      prediction techniques are brought to bear on the problem of constructing a genome
      annotation as manual annotation is extremely time-consuming and costly. This
      chapter reviews the methods by which the individual components of a typical gene
      structure are detected in genomic sequence and then discusses several popular
      statistical frameworks for integrated gene prediction on eukaryotic genome
      sequences.

PMID- 22407710
TI  - Alignment methods: strategies, challenges, benchmarking, and comparative
      overview.
AB  - Comparative evolutionary analyses of molecular sequences are solely based on the
      identities and differences detected between homologous characters. Errors in this
      homology statement, that is errors in the alignment of the sequences, are likely
      to lead to errors in the downstream analyses. Sequence alignment and phylogenetic
      inference are tightly connected and many popular alignment programs use the
      phylogeny to divide the alignment problem into smaller tasks. They then neglect
      the phylogenetic tree, however, and produce alignments that are not
      evolutionarily meaningful. The use of phylogeny-aware methods reduces the error
      but the resulting alignments, with evolutionarily correct representation of
      homology, can challenge the existing practices and methods for viewing and
      visualising the sequences. The inter-dependency of alignment and phylogeny can be
      resolved by joint estimation of the two; methods based on statistical models
      allow for inferring the alignment parameters from the data and correctly take
      into account the uncertainty of the solution but remain computationally
      challenging. Widely used alignment methods are based on heuristic algorithms and
      unlikely to find globally optimal solutions. The whole concept of one correct
      alignment for the sequences is questionable, however, as there typically exist
      vast numbers of alternative, roughly equally good alignments that should also be
      considered. This uncertainty is hidden by many popular alignment programs and is
      rarely correctly taken into account in the downstream analyses. The quest for
      finding and improving the alignment solution is complicated by the lack of
      suitable measures of alignment goodness. The difficulty of comparing alternative
      solutions also affects benchmarks of alignment methods and the results strongly
      depend on the measure used. As the effects of alignment error cannot be
      predicted, comparing the alignments' performance in downstream analyses is
      recommended.

PMID- 22407711
TI  - Whole-genome alignment.
AB  - Whole-genome alignment (WGA) is the prediction of evolutionary relationships at
      the nucleotide level between two or more genomes. It combines aspects of both
      colinear sequence alignment and gene orthology prediction, and is typically more
      challenging to address than either of these tasks due to the size and complexity
      of whole genomes. Despite the difficulty of this problem, numerous methods have
      been developed for its solution because WGAs are valuable for genome-wide
      analyses, such as phylogenetic inference, genome annotation, and function
      prediction. In this chapter, we discuss the meaning and significance of WGA and
      present an overview of the methods that address it. We also examine the problem
      of evaluating whole-genome aligners and offer a set of methodological challenges
      that need to be tackled in order to make the most effective use of our rapidly
      growing databases of whole genomes.

PMID- 22407712
TI  - Inferring orthology and paralogy.
AB  - The distinction between orthologs and paralogs, genes that started diverging by
      speciation versus duplication, is relevant in a wide range of contexts, most
      notably phylogenetic tree inference and protein function annotation. In this
      chapter, we provide an overview of the methods used to infer orthology and
      paralogy. We survey both graph-based approaches (and their various grouping
      strategies) and tree-based approaches, which solve the more general problem of
      gene/species tree reconciliation. We discuss conceptual differences among the
      various orthology inference methods and databases, and examine the difficult
      issue of verifying and benchmarking orthology predictions. Finally, we review
      typical applications of orthologous genes, groups, and reconciled trees and
      conclude with thoughts on future methodological developments.

PMID- 22407713
TI  - Detecting laterally transferred genes.
AB  - Methods for identifying alien genes in genomes fall into two general classes.
      Phylogenetic methods examine the distribution of a gene's homologues among
      genomes to find those with relationships not consistent with vertical
      inheritance. These approaches include identifying orphan genes which lack
      homologues in closely related genomes and genes with unduly high levels of
      similarity to genes in otherwise unrelated genomes. Rigorous statistical tests
      are available to place confidence intervals for predicted alien genes. Parametric
      methods examine the compositional properties of genes within a genome to find
      those with atypical properties, likely indicating the directional mutational
      pressures of a donor genome. These methods may compare the properties of genes to
      genomic averages, properties of genes to each other, or properties of large,
      multigene regions of the chromosome. Here, we discuss the strengths and
      weaknesses of each approach.

PMID- 22407714
TI  - Genome evolution in outcrossing versus selfing versus asexual species.
AB  - A major current molecular evolution challenge is to link comparative genomic
      patterns to species' biology and ecology. Breeding systems are pivotal because
      they affect many population genetic processes, and thus genome evolution. We
      review theoretical predictions and empirical evidence about molecular
      evolutionary processes under three distinct breeding systems-outcrossing,
      selfing, and asexuality. Breeding systems may have a profound impact on genome
      evolution, including molecular evolutionary rates, base composition, genomic
      conflict, and possibly genome size. However, while asexual species essentially
      conform to theoretical predictions, the situation is less simple in selfing
      species. We discuss the possible reasons to potentially explain this paradox. In
      reverse, comparative and population genomic data and approaches help revisiting
      old questions on the long-term evolution of breeding systems.

PMID- 22407715
TI  - Transposable elements and their identification.
AB  - Most genomes are populated by thousands of sequences that originated from mobile
      elements. On the one hand, these sequences present a real challenge in the
      process of genome analysis and annotation. On the other hand, there are very
      interesting biological subjects involved in many cellular processes. Here, we
      present an overview of transposable elements (TEs) biodiversity and their impact
      on genomic evolution. Finally, we discuss different approaches to the TEs
      detection and analyses.

PMID- 22407716
TI  - Evolution of genome content: population dynamics of transposable elements in
      flies and humans.
AB  - Recent research is starting to shed light on the factors that influence the
      population and evolutionary dynamics of transposable elements (TEs) and TE life
      cycles. Genomes differ sharply in the number of TE copies, in the level of TE
      activity, in the diversity of TE families and types, and in the proportion of old
      and young TEs. In this chapter, we focus on two well-studied genomes with
      strikingly different architectures, humans and Drosophila, which represent two
      extremes in terms of TE diversity and population dynamics. We argue that some of
      the answers might lie in (1) the larger population size and consequently more
      effective selection against new TE insertions due to ectopic recombination in
      flies compared to humans; and (2) in the faster rate of DNA loss in flies
      compared to humans leading to much faster removal of fixed TE copies from the fly
      genome.

PMID- 22407717
TI  - Detection and phylogenetic assessment of conserved synteny derived from whole
      genome duplications.
AB  - Identification of intragenomic conservation of gene compositions in multiple
      chromosomal segments led to evidence of whole genome (WGDs) duplications. The
      process by which WGDs have been maintained and decayed provides us with clues for
      understanding how the genome evolves. In this chapter, we summarize current
      understanding of phylogenetic distribution and evolutionary impact of WGDs,
      introduce basic procedures to detect conserved synteny, and discuss typical
      pitfalls, as well as biological insights.

PMID- 22407718
TI  - Analysis of gene order evolution beyond single-copy genes.
AB  - The purpose of this chapter is to provide a comprehensive review of the field of
      genome rearrangement, i.e., comparative genomics, based on the representation of
      genomes as ordered sequences of signed genes. We specifically focus on the "hard
      part" of genome rearrangement, how to handle duplicated genes. The main questions
      are: how have present-day genomes evolved from a common ancestor? What are the
      most realistic evolutionary scenarios explaining the observed gene orders? What
      was the content and structure of ancestral genomes? We aim to provide a concise
      but complete overview of the field, starting with the practical problem of
      finding an appropriate representation of a genome as a sequence of ordered genes
      or blocks, namely the problems of orthology, paralogy, and synteny block
      identification. We then consider three levels of gene organization: the gene
      family level (evolution by duplication, loss, and speciation), the cluster level
      (evolution by tandem duplications), and the genome level (all types of
      rearrangement events, including whole genome duplication).

PMID- 22407719
TI  - Discovering patterns in gene order.
AB  - Various genetic events during the process of natural evolution shape the
      landscape of the genomes. In this chapter, we explore an approach to
      investigating multiple genomes in order to unravel their complex relationships
      that go beyond their placement on a phylogeny. To this end, we treat genes as the
      smallest syntactic unit on the genome and explore their relative organization
      across multiple genomes. In the first half of the chapter, we discuss
      mathematical models to capture the combinatorial structures of this relative
      organization and statistical models to study their distributions. In the second
      half of the chapter, we apply these models to analyze the relationship between
      three closely related plant genomes.

PMID- 22407720
TI  - Secreted luciferase for in vivo evaluation of systemic protein delivery in mice.
AB  - A naturally secreted Gaussia luciferase (Gluc) has been utilized as a reporter
      for bioluminescence imaging (BLI) evaluation. However, the potential application
      of Gluc for in vivo monitoring of systemic protein delivery, as well as its
      natural biodistribution, has not been studied. To examine Gluc secretion and
      uptake profile, we injected Gluc-encoding plasmids into mice by hydrodynamic tail
      vein injection. Whole-body BLI showed that imaging quantification obtained at
      pawpad was directly correlated to blood Gluc activities. When gene expression was
      restricted to the liver by the use of a hepatic promoter, in vivo Gluc
      biodistribution analysis revealed the kidney/bladder, stomach/intestine, and lung
      as the major uptake organs. Three-dimensional BLI identified liver/stomach and
      lung as the main internal luminescent sources, demonstrating the feasibility of
      detecting major uptake organs in live animals by 3D BLI with high-background
      signals in circulation. Notably, Gluc levels in capillary-depleted brain samples
      from Gluc-injected mice were comparable to controls, suggesting that Gluc may not
      cross the blood-brain barrier. Gluc uptake kinetics and intracellular half-life
      were assessed in various types of cell lines, implicating the involvement of non
      specific pinocytosis. These results suggest that Gluc-based system may provide a
      useful tool for in vivo evaluation of protein/agent biodistribution following
      systemic delivery.

PMID- 22407721
TI  - Extra EF hand unit (DX) mediated stabilization and calcium independency of alpha
      amylase.
AB  - It is the common feature of alpha-amylases that calcium ion is required for their
      structural integrity and thermal stability. All amylases have at least one Ca(2+)
      per molecule; therefore amino acids involved in calcium binding are specific and
      conserved. In this study, sequence analysis revealed the presence of EF-hand-like
      motif in calcium-binding loop of Bacillus megaterium WHO (BMW)-amylase that was
      previously isolated from BMW. The EF-hand motif and its variants (EF-hand-like
      motif) are the most common calcium-binding motifs found in a large number of
      protein families. To investigate the effect of calcium ion on the thermal
      stability and activity of BMW-amylase, we used site-directed mutagenesis to
      replace histidine 58 with Asp (D), Ile (I), Tyr (Y), Phe (F), and Arg (R) at the
      seventh position of EF-hand-like motif. Upon the addition of an extra DX unit to
      the calcium-binding loop in H58D variant, thermal stability, catalytic activity,
      and chelating power of the enzyme improved due to higher affinity toward calcium.
      H58D variant demonstrated calcium independency compared to the wild type and
      other created mutants. Conformational changes in the presence and absence of
      Ca(2+) were monitored using fluorescence technique.

PMID- 22407722
TI  - Evidences for an alternative genealogy of 'Sangiovese'.
AB  - Two different hypothesis for the parentage of 'Sangiovese', the most important
      and widespread Italian winegrape, have been proposed by some previous studies. We
      screened our grapevine collection, mostly comprising south Italian cultivars
      collected to preserve biodiversity, to asses kinships. Surprisingly we found two
      previously unreported candidate parents for 'Sangiovese'. The first putative
      parent is 'Ciliegiolo' a well know variety already addressed as relative of
      'Sangiovese'; the second putative parent is 'Negrodolce', an old local variety we
      recovered and was considered lost during the last century. In order to obtain a
      stronger statistical support for this new kinship, we tested seventy different
      microsatellite markers but only 57 were found reliable. The new proposed
      parentage stood well even with such a in depth molecular analysis whereas only
      one discrepancy was found in one of the 57 microsatellite marker analyzed. This
      discrepancy is certainly due to a null-allele and therefore it should not impair
      our hypothesis but it points out limits of the microsatellites profiling as a
      pedigree research method considering that this is the third different kinship
      proposed so far for 'Sangiovese'. Thus in this article, by means of detailed
      molecular fingerprinting, we provide a completely new strong evidence for a south
      Italian origin of 'Sangiovese' and we discuss our findings comparing our data
      with those previously reported by other authors.

PMID- 22407723
TI  - Optimization of the transductional efficiency of lentiviral vectors: effect of
      sera and polycations.
AB  - Lentiviral vectors are widely used as effective gene-delivery vehicles.
      Optimization of the conditions for efficient lentiviral transduction is of a high
      importance for a variety of research applications. Presence of positively charged
      polycations reduces the electrostatic repulsion forces between a negatively
      charged cell and an approaching enveloped lentiviral particle resulting in an
      increase in the transduction efficiency. Although a variety of polycations are
      commonly used to enhance the transduction with retroviruses, the relative effect
      of various types of polycations on the efficiency of transduction and on the
      potential bias in the determination of titer of lentiviral vectors is not fully
      understood. Here, we present data suggesting that DEAE-dextran provides superior
      results in enhancing lentiviral transduction of most tested cell lines and
      primary cell cultures. Specific type and source of serum affects the efficiency
      of transduction of target cell populations. Non-specific binding of enhanced
      green fluorescent protein (EGFP)-containing membrane aggregates in the presence
      of DEAE-dextran does not significantly affect the determination of the titer of
      EGFP-expressing lentiviral vectors. In conclusion, various polycations and types
      of sera should be tested when optimizing lentiviral transduction of target cell
      populations.

PMID- 22407724
TI  - Antagonism between extreme negative linear compression and spin crossover in
      [Fe(dpp)(2)(NCS)(2)]?py.
AB  - A scissor-like geometric mechanism is responsible for the strongest negative
      linear compression effect yet observed in a molecular material,
      [Fe(dpp)(2)(NCS)(2)]?py (see picture; dpp=dipyrido[3,2-a:2'3'-c]phenazine), C
      gray, N blue, S yellow, Fe red). The same mechanism is also responsible for
      suppressing the high-spin to low-spin transition under pressure.

PMID- 22407725
TI  - Assessment of the high-dose concept and level of control provided by MON 87701 *
      MON 89788 soybean against Anticarsia gemmatalis and Pseudoplusia includens
      (Lepidoptera: Noctuidae) in Brazil.
AB  - BACKGROUND: Genetically modified MON 87701 * MON 89788 soybean (Glycine max),
      which expresses the Cry1Ac and EPSP-synthase proteins, has been registered for
      commercial use in Brazil. To develop an Insect Resistance Management (IRM)
      program for this event, laboratory and field studies were conducted to assess the
      high-dose concept and level of control it provides against Anticarsia gemmatalis
      and Pseudoplusia includens. RESULTS: The purified Cry1Ac protein was more active
      against A. gemmatalis [LC(50) (FL 95%) = 0.23 (0.15-0.34) ug Cry1Ac mL(-1) diet]
      than P. includens [LC(50) (FL 95%) = 3.72 (2.65-4.86) ug Cry1Ac mL(-1) diet]. In
      bioassays with freeze-dried MON 87701 * MON 89788 soybean tissue diluted 25 times
      in an artificial diet, there was 100% mortality of A. gemmatalis and up to 95.79%
      mortality for P. includens. In leaf-disc bioassays and under conditions of high
      artificial infestation in the greenhouse and natural infestation in the field,
      MON 87701 * MON 89788 soybean showed a high level of efficacy against both target
      pests. CONCLUSIONS: The MON 87701 * MON 89788 soybean provides a high level of
      control against A. gemmatalis and P. includes, but a high-dose event only to A.
      gemmatalis.

PMID- 22407727
TI  - Using the magnetosome to model effective gene-based contrast for magnetic
      resonance imaging.
AB  - Formation of iron biominerals is a naturally occurring phenomenon, particularly
      among magnetotactic bacteria which produce magnetite (Fe(3) O(4) ) in a
      subcellular compartment termed the magnetosome. Under the control of numerous
      genes, the magnetosome serves as a model upon which to (1) develop gene-based
      contrast in mammalian cells and (2) provide a mechanism for reporter gene
      expression in magnetic resonance imaging (MRI). There are two main components to
      the magnetosome: the biomineral and the lipid bilayer that surrounds it. Both are
      essential for magnetotaxis in a variety of magnetotactic bacteria, but
      nonessential for cell survival. Through comparative genome analysis, a subset of
      genes characteristic of the magnetotactic phenotype has been found both within
      and outside a magnetosome genomic island. The functions of magnetosome-associated
      proteins reflect the complex nature of this intracellular structure and include
      vesicle formation, cytoskeletal attachment, iron transport, and crystallization.
      Examination of magnetosome genes and structure indicates a protein-directed and
      stepwise assembly of the magnetosome compartment. Attachment of magnetosomes
      along a cytoskeletal filament aligns the magnetic particles such that the cell
      may be propelled along an external magnetic field. Interest in this form of
      magnetotaxis has prompted research in several areas of medicine, including
      magnetotactic bacterial targeting of tumors, MR-guided movement of magnetosome
      bearing cells through vessels and molecular imaging of mammalian cells using MRI,
      and its hybrid modalities. The potential adaptation of magnetosome genes for
      noninvasive medical imaging provides new opportunities for development of
      reporter gene expression for MRI.

PMID- 22407726
TI  - Microcephaly, intellectual impairment, bilateral vesicoureteral reflux,
      distichiasis, and glomuvenous malformations associated with a 16q24.3 contiguous
      gene deletion and a Glomulin mutation.
AB  - Two hereditary syndromes, lymphedema-distichiasis (LD) syndrome and blepharo
      chelio-dontic (BCD) syndrome include the aberrant growth of eyelashes from the
      meibomian glands, known as distichiasis. LD is an autosomal dominant syndrome
      primarily characterized by distichiasis and the onset of lymphedema usually
      during puberty. Mutations in the forkhead transcription factor FOXC2 are the only
      known cause of LD. BCD syndrome consists of autosomal dominant abnormalities of
      the eyelid, lip, and teeth, and the etiology remains unknown. In this report, we
      describe a proband that presented with distichiasis, microcephaly, bilateral
      grade IV vesicoureteral reflux requiring ureteral re-implantation, mild
      intellectual impairment and apparent glomuvenous malformations (GVM).
      Distichiasis was present in three generations of the proband's maternal side of
      the family. The GVMs were severe in the proband, and maternal family members
      exhibited lower extremity varicosities of variable degree. A GLMN (glomulin) gene
      mutation was identified in the proband that accounts for the observed GVMs; no
      other family member could be tested. TIE2 sequencing revealed no mutations. In
      the proband, an additional submicroscopic 265 kb contiguous gene deletion was
      identified in 16q24.3, located 609 kb distal to the FOXC2 locus, which was
      inherited from the proband's mother. The deletion includes the C16ORF95, FBXO31,
      MAP1LC3B, and ZCCHC14 loci and 115 kb of a gene desert distal to FOXC2 and FOXL1.
      Thus, it is likely that the microcephaly, distichiasis, vesicoureteral, and
      intellectual impairment in this family may be caused by the deletion of one or
      more of these genes and/or deletion of distant cis-regulatory elements of FOXC2
      expression.

PMID- 22407728
TI  - Electron microscopic observations on the alterations of tegumental surface of
      Raillietina echinobothrida treated with root-peel extract of Potentilla fulgens.
AB  - Potentilla fulgens, a member of the family Rosaceae, has been known since ancient
      times in Northeast India for its antiparasitic, antitumour and antidiabetic
      properties. The crude ethanolic extract of the plant was assayed against
      Raillietina echinobothrida, the intestinal cestode parasite of domestic fowl to
      authenticate the putative anthelmintic efficacy and cestocidal potential in
      particular of the plant. Treatment of the worm in-vitro with 25, 50 and 100 mg of
      crude extract per ml of phosphate buffered saline caused paralysis leading to
      death taking 4.02-4.20, 3.05-3.75 and 2.05-2.83 h respectively. Scanning electron
      microscopic observations on treated worms revealed deformation of surface
      architecture, particularly in scolex and surface microtriches. Severe distortion
      and disorganization of the tegumental and subtegumental layer along with
      cytoplasmic organelle was also observed under transmission electron microscope.
      The possible use of the plant as a potential anthelmintic against cestode
      parasite is discussed.

PMID- 22407729
TI  - Phenotypic fidelity (or not?) of epithelial cells in the liver.

PMID- 22407730
TI  - Cognitive impairment in late life schizophrenia and bipolar I disorder.
AB  - OBJECTIVE: Evidence in younger populations suggests quantitative but not
      categorical differences in cognitive impairments between schizophrenia and
      bipolar disorder. It is uncertain whether a similar distinction applies to
      patients in later life. METHODS: We compared the cognitive abilities of older,
      community-living schizophrenia patients, controlling for their state of
      symptomatic remission, with those of older euthymic patients with bipolar I
      disorder. The study included 67 patients with schizophrenia (20 in symptomatic
      remission, 47 not in symptomatic remission; mean age 68 years) and 74 euthymic
      bipolar I patients (mean age 70 years), who were compared using analysis of
      covariance on clinical and neuropsychological variables (e.g., attention/working
      memory, verbal memory, executive function and verbal fluency) and contrasted with
      69 healthy controls. RESULTS: Remitted (SR) and non-remitted (SN) schizophrenia
      patients and bipolar I (BP) patients were impaired relative to healthy controls,
      with mostly large effect sizes for verbal memory (Cohen's d: SR 1.34, SN 1.48, BP
      1.09), executive function (Cohen's d: SR 0.87, SN 1.29, BP 0.71) and verbal
      fluency (Cohen's d: SR 1.09, SN 1.25, BP 0.88), but smaller effect sizes for the
      domain of attention/working memory (Cohen's d: SR 0.26, SN 0.18, BP 0.52).
      Differences in cognitive performance between the remitted schizophrenia patients
      and the bipolar I patients were not significant. CONCLUSIONS: In both older
      patients with schizophrenia and with bipolar disorder, serious and pervasive
      cognitive deficits can be demonstrated. Trait-related cognitive deficits in
      schizophrenia and bipolar disorder may share major phenotypic similarity in later
      life.

PMID- 22407731
TI  - Graphene functionalisation with a conjugated poly(fluorene) by click coupling:
      striking electronic properties in solution.
AB  - Graphene flakes covalently modified with a conjugated polymer, poly[(9,9
      dihexylfluorene)-co-alt-(9,9-bis-(6-azidohexyl)fluorene)] (PFA), were efficiently
      synthesised by a Cu-catalysed Huisgen 1,3-dipolar cycloaddition between alkyne
      modified graphene and an azide-functionalised polymer. Two approaches for the
      modification of graphene with alkyne groups were investigated (coupling with a
      diazonium salt generated in situ or an amidation reaction) and the optimum
      conditions determined. The success of the click-coupling approach was confirmed
      by FTIR, (1)H NMR, Raman, and X-ray photoelectron spectroscopy (XPS). The
      absorption and emission spectra of the click product show a strong solvent
      dependency.

PMID- 22407732
TI  - Property-performance control of multidimensional, hierarchical, single
      crystalline ZnO nanoarchitectures.
AB  - Diverse morphologies of multidimensional hierarchical single-crystalline ZnO
      nanoarchitectures including nanoflowers, nanobelts, and nanowires are obtained by
      use of a simple thermal evaporation and vapour-phase transport deposition
      technique by placing Au-coated silicon substrates in different positions inside a
      furnace at process temperatures as low as 550  degrees C. The nucleation and
      growth of ZnO nanostructures are governed by the vapour-solid mechanism, as
      opposed to the commonly reported vapour-liquid-solid mechanism, when gold is used
      in the process. The morphological, structural, compositional and optical
      properties of the synthesized ZnO nanostructures can be effectively tailored by
      means of the experimental parameters, and these properties are closely related to
      the local growth temperature and gas-phase supersaturation at the sample
      position. In particular, room-temperature photoluminescence measurements reveal
      an intense near-band-edge ultraviolet emission at about 386 nm for nanobelts and
      nanoflowers, which suggests that these nanostructures are of sufficient quality
      for applications in, for example, optoelectronic devices.

PMID- 22407733
TI  - Oliveridepsidones A-D, antioxidant depsidones from Garcinia oliveri.
AB  - Four new prenylated depsidones, oliveridepsidones A-D, were isolated from the
      bark of Garcinia oliveri collected in Vietnam. Their structures were elucidated
      using mainly NMR techniques ((1)H and (13)C NMR, HMQC, HMBC and NOE experiments).

PMID- 22407734
TI  - Virtual autopsy by computed tomographic angiography of the fetal heart: a
      feasibility study.
AB  - OBJECTIVE: To determine the feasibility of postmortem computed tomographic (pm
      CT) angiography for fetal heart evaluation. METHODS: Following termination of
      pregnancy (TOP) or intrauterine fetal death (IUFD) beyond 18 weeks' gestation, 33
      fetuses were examined by pm-CT; in eight contrast medium was injected through the
      umbilical cord and in 25 contrast medium was injected directly into the heart.
      Logistic regression analysis was used to investigate the effect on the ability to
      visualize cardiac structures on pm-CT angiography of gestational age at TOP or
      delivery following IUFD, the time delay between fetal death and examination, the
      technique used for contrast-medium injection, the presence of cardiac
      abnormalities and whether or not there was IUFD. The diagnostic accuracy of pm-CT
      angiography for the evaluation of fetal cardiac structures was also evaluated.
      RESULTS: Cardiac anatomy including heart situs, the four-chamber view and great
      vessels could be visualized on pm-CT angiography in 29 out of 33 fetuses (87.9%).
      Logistic regression analysis showed that the ability to visualize cardiac
      structures on pm-CT angiography was positively correlated only with contrast
      medium injected directly into the heart. Twenty-five out of the 33 fetuses
      underwent conventional autopsy. There were five cases with suspected major
      cardiac abnormality at prenatal ultrasound and one with a minor cardiac
      abnormality. In one of these cases, severe leakage into the pleural cavity did
      not allow for visualization of any heart structure on pm-CT angiography and in
      another invasive autopsy was declined. In two of the remaining four cases, the
      findings on pm-CT angiography and invasive autopsy were in agreement, while in
      two a ventricular septal defect was found on invasive autopsy but not on pm-CT.
      None of the 27 cases with normal hearts was falsely classified as abnormal using
      pm-CT angiography. CONCLUSION: Pm-CT angiography by direct injection into the
      heart seems to be a feasible method for its evaluation. The extent to which such
      a technique could be used for the evaluation of congenital heart disease as an
      alternative to classical postmortem autopsy remains to be determined.

PMID- 22407735
TI  - The men of Nelson's navy: a comparative stable isotope dietary study of late 18th
      century and early 19th century servicemen from Royal Naval Hospital burial
      grounds at Plymouth and Gosport, England.
AB  - We present stable isotopic analyses of collagen from 80 servicemen excavated from
      the late 18th/early 19th century naval hospitals at Plymouth (50) and Haslar,
      Gosport (30) in southern England. Historical records suggest that, the diets of
      these two populations should be essentially identical. While delta(15) N of the
      rib collagen confirmed that naval servicemen were relatively well-catered for in
      terms of meat allowance (Plymouth average delta(15) N = 11.10/00, Gosport =
      11.90/00), stable carbon isotope analysis produced average values for the two
      assemblages, which were significantly different (Plymouth average delta(13) C = 
      18.80/00, Gosport = -20.00/00). We postulate that these differences stem from
      divergent naval postings, with a greater proportion of Plymouth individuals
      serving in areas that entailed a greater input of C(4) foodstuffs. By comparison
      with published data from approximately contemporary burials at Snake Hill,
      Ontario, Canada and Chesapeake Bay, Virginia, we suggest that this area is the
      east coast of North America. For 15 of the 30 individuals from Gosport, we have
      data on ribs, femur, and dentine from the same skeleton, which appear to show
      that they came from a variety of locations in their preadolescence, but converged
      in dietary terms onto a "naval average," which is consistent with historical
      evidence for recruitment patterns into the Navy at the time. By comparison with
      published data from skeletons recovered from the wreck of the Mary Rose (sank
      1545), we conclude that this naval diet was virtually unchanged from the 16th
      century to the end of the 18th century.

PMID- 22407738
TI  - Investigation of the immunomodulatory potential of oryzanol isolated from crude
      rice bran oil in experimental animal models.
AB  - Nutrition and nutritional status can influence the development, maintenance and
      optimal functioning of the immune system. Oryzanol (OZ), a commercially important
      bioactive phytochemical component of rice bran oil, has generated global interest
      on account of its several beneficial physiological effects on human health. The
      aim of the present investigation was to examine the effect of OZ, isolated from
      crude rice bran oil (cRBO), on the regulation of the immune response in
      experimental animal models. The isolated OZ was identified with respect to the
      standard by melting point determination, thin-layer chromatography (TLC), UV
      visible spectrophotometry and high-performance liquid chromatography (HPLC).
      Cellular immunity in rats was assessed by carbon clearance assay, delayed-type
      hypersensitivity (DTH) response and cyclophosphamide-induced myelosuppression,
      whereas humoral immunity was analysed by haemagglutinating antibody (HA) titre
      assay. Oryzanol (25, 50 and 100 mg/kg, p.o.) evoked a significant increase in
      antibody titre values in the haemagglutination test and potentiated the delayed
      type hypersensitivity reaction induced by sheep red blood cells. It also
      significantly ameliorated myelosuppression in cyclophosphamide treated rats and
      showed an increase in phagocytic index in the carbon clearance assay. The
      findings from the study indicate that OZ possesses sufficient potential for
      augmenting immune activity by cellular and humoral mediated mechanisms.

PMID- 22407736
TI  - NF-kappaB inhibition significantly upregulates the norepinephrine transporter
      system, causes apoptosis in pheochromocytoma cell lines and prevents metastasis
      in an animal model.
AB  - Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are specific types of
      neuroendocrine tumors that originate in the adrenal medulla or
      sympathetic/parasympathetic paraganglia, respectively. Although these tumors are
      intensively studied, a very effective treatment for metastatic PHEO or PGL has
      not yet been established. Preclinical evaluations of novel therapies for these
      tumors are very much required. Therefore, in this study we tested the effect of
      triptolide (TTL), a potent nuclear factor-kappaB (NF-kappaB) inhibitor, on the
      cell membrane norepinephrine transporter (NET) system, considered to be the
      gatekeeper for the radiotherapeutic agent 131I-metaiodobenzylguanidine (131I
      MIBG). We measured changes in the mRNA and protein levels of NET and correlated
      them with proapoptotic factors and metastasis inhibition. The study was performed
      on three different stable PHEO cell lines. We found that blocking NF-kappaB with
      TTL or capsaicin increased both NET mRNA and protein levels. Involvement of NF
      kappaB in the upregulation of NET was verified by mRNA silencing of this site and
      also by using NF-kappaB antipeptide. Moreover, in vivo treatment with TTL
      significantly reduced metastatic burden in an animal model of metastatic PHEO.
      The present study for the first time shows how NF-kappaB inhibitors could be
      successfully used in the treatment of metastatic PHEO/PGL by a significant
      upregulation of NET to increase the efficacy of 131I-MIBG and by the induction of
      apoptosis.

PMID- 22407739
TI  - Scintigraphy at 3 months after single lung transplantation and observations of
      primary graft dysfunction and lung function.
AB  - Scintigraphy has been used as a tool to detect dysfunction of the lung before and
      after transplantation. The aims of this study were to evaluate the development of
      the ventilation-perfusion relationships in single lung transplant recipients in
      the first year, at 3 months after transplantation, and to investigate whether
      scintigraphic findings at 3 months were predictive for the outcome at 12 months
      in relation to primary graft dysfunction (PGD) and lung function. A retrospective
      study was carried out on all patients who prospectively and consecutively were
      referred for a routine lung scintigraphy procedure 3 months after single lung
      transplantation (SLTX). A total of 41 patients were included in the study: 20
      women and 21 men with the age span of patients at transplantation being 38-66
      years (mean +/- SD: 54.2 +/- 6.0). Patient records also included lung function
      tests and chest X-ray images. We found no significant correlation between lung
      function distribution at 3 months and PGD at 72 h. There was also no significant
      correlation between PGD scores at 72 h and lung function at 6 and 12 months. The
      same applied to scintigraphic scores for heterogeneity at 3 months compared with
      lung function at 6 and 12 months. Fifty-five percent of all patients had
      decreased ventilation function measured in the period from 6 to 12 months. Forty
      nine percent of the patients had normal perfusion evaluations, and 51% had
      abnormal perfusion evaluations at 3 months. For ventilation evaluations, 72% were
      normal and 28% were abnormal. There was a significant difference in the normal
      versus abnormal perfusion and ventilation scintigraphic images evaluated from the
      same patients. Ventilation was distributed more homogenously in the transplanted
      lung than perfusion in the same lung. The relative distribution of perfusion and
      ventilation to the transplanted lung of patients with and without a primary
      diagnosis of fibrosis did not differ significantly from each other. We conclude
      that PGD defined at 72 h does not lead to recognizable changes in ventilation
      perfusion scintigrapy at 3 months, and scintigraphic findings do not correlate
      with development in lung function in the first 12 months.

PMID- 22407740
TI  - Corticosteroids and rituximab as adjunctive treatments for thrombotic
      thrombocytopenic purpura.
AB  - Although treatment with plasma exchange increased the survival of patients with
      thrombotic thrombocytopenia purpura to 80% in the 1980s, no further increase of
      survival occurred over the next 20 years. However, more consistent use of
      adjuvant treatment with corticosteroids and rituximab in recent years has begun
      to further increase survival as well as decrease the frequency of relapse. With
      adjuvant treatment, durable remissions can be achieved more quickly, requiring
      fewer days of plasma exchange. Fewer days of plasma exchange have resulted in
      fewer complications, such as central venous catheter-related systemic infections.
      Future potential options for adjuvant treatment, recombinant ADAMTS13 to correct
      severe ADAMTS13 deficiency, and agents to block von Willebrand factor-mediated
      platelet thrombosis are being investigated.

PMID- 22407741
TI  - Meta-analyses: what they can and cannot do.
AB  - Meta-analyses overcome the limitation of small sample sizes or rare outcomes by
      pooling results from a number of individual studies to generate a single best
      estimate. As long as a meta-analysis is not limited by poor quality of included
      trials, unexplainable heterogeneity and/or reporting bias of individual trials,
      meta-analyses can be instrumental in reliably demonstrating benefit or harm of an
      intervention when results of individual randomised controlled trials are
      conflicting or inconclusive. Therefore meta-analyses should be conducted as part
      of a systematic review, i.e., a systematic approach to answer a focused clinical
      question. Important features of a systematic review are a comprehensive,
      reproducible search for primary studies, selection of studies using clear and
      transparent eligibility criteria, standardised critical appraisal of studies for
      quality, and investigation of heterogeneity among included studies.  Cumulative
      meta-analysis may prevent delays in the introduction of effective treatments and
      may allow for early detection of harmful effects of interventions. As opposed to
      meta-analysis based on aggregate study data, individual patient data meta
      analyses offer the advantage to use standardised criteria across trials and
      reliably investigate subgroup effects of interventions. Network meta-analysis
      allows the integration of data from direct and indirect comparisons in order to
      compare multiple treatments in a comprehensive analysis and determine the best
      treatment among several options.  We conclude that meta-analysis has become a
      popular, versatile, and powerful tool. If rigorously conducted as part of a
      systematic review, it is essential for evidence-based decision making in clinical
      practice as well as on the health policy level.

PMID- 22407742
TI  - Degenerative process and cell death in salivary glands of Rhipicephalus
      sanguineus (Latreille, 1806) (Acari: Ixodidae) semi-engorged female exposed to
      the acaricide permethrin.
AB  - Ticks are ectoparasites of great medical and veterinary importance around the
      world and synthetic chemicals such as permethrin have been used for their
      control. This study provides a cytochemistry analysis of both degenerative and
      cell death processes in salivary glands of the brown dog tick Rhipicephalus
      sanguineus semi-engorged females exposed to 206, 1,031, and 2,062 ppm of
      permethrin. The results presented herein demonstrate that permethrin is a potent
      chemical acaricide that would act on the glandular tissue's morphophysiology in
      this tick species by eliciting severe changes in the acinus shape, intense
      vacuolation of the acinar cells' cytoplasm, marked glandular tissue
      disorganization, culminating in an advanced degenerative stage with consequent
      formation of many apoptotic bodies (cell death). In addition, permethrin induced
      major changes in the acinar cells' nucleus, such as a change both in its shape
      and size, chromatin marginalization, nuclear fragmentation, and appearance of
      picnotic nuclei, especially when the highest concentrations of the product were
      used. Thus, permethrin induced early degeneration of this tissue characterized by
      significant changes in the structure of acinar cells and production of enzymes
      related to the cell death process, in addition to interfering directly in the
      genetic material of these cells.

PMID- 22407743
TI  - Grief reactions in dementia carers: a systematic review.
AB  - OBJECTIVE: Supporting dementia carers is an identified target of the UK
      government, yet we know little about such family carers' grief before and after
      the death of the person with dementia for whom they care. We systematically
      review the existing literature on characteristics, prevalence, predictors and
      associations of grief in dementia carers before and after death. METHODS: We
      searched electronic databases and found 31 publications meeting predetermined
      criteria. RESULTS: Grief in dementia carers, which may be normal or complicated,
      is a complex reaction to losses occurring before and after death. Carers
      experience anticipatory grief as multiple losses for themselves (companionship,
      personal freedom and control) and the person with dementia. Anticipation and
      ambiguity about the future, anger, frustration and guilt are core features.
      Anticipatory grief is greatest in moderate to severe stage dementia and spouse
      carers, especially when the person with dementia is institutionalised. There was
      poor quality evidence about the prevalence of grief; studies reported
      anticipatory grief between 47% and 71%, and complicated grief after death is
      estimated around 20%. Carer depression increases with anticipatory grief. Being a
      spouse carer and being depressed are the strongest predictors of complicated and
      normal grief after death. CONCLUSION: Grief in dementia carers can be expected;
      however, those at risk of distressing anticipatory and complicated grief may be
      identified and targeted for intervention when necessary. Higher quality research
      from a wider range of samples and countries is needed to explore this complex and
      emergent topic.

PMID- 22407744
TI  - Myopathy in a 20-year-old female patient with D4ST-1 deficient Ehlers-Danlos
      syndrome due to a homozygous CHST14 mutation.
AB  - We here report on a 20-year-old female patient with EDS due to a homozygous
      CHST14 single nucleotide deletion resulting in D4ST-1 deficiency, accompanied by
      muscle hypoplasia and muscle weakness. Findings of muscle ultrasound,
      electromyography, and muscle biopsy pointed to a myopathy, similarly as in other
      EDS types. This myopathy probably contributes to the gross motor developmental
      delay in this type of EDS.

PMID- 22407745
TI  - A screening method to assess biological effects of microRNA overexpression in
      Chinese hamster ovary cells.
AB  - MicroRNAs (miRNAs) are a novel class of short non-coding RNAs, which negatively
      regulate target gene expression at post-transcriptional level. They mediate an
      important layer of control in the global regulation of gene networks, controlling
      a broad range of physiological as well as patho-physiological pathways including
      development, cancer, metabolism, proliferation, and stress resistance. So far,
      more than 365 miRNA genes have been identified in CHO cells. The functional
      analysis of the physiological effect of such large numbers of miRNAs, however,
      requires an efficient functional screening method. In the current study, we
      therefore established and evaluated a protocol to perform miRNA overexpression
      and to screen their effect on bio-industrially relevant phenotypes, such as
      growth, viability and productivity, using a recombinant, Epo-Fc producing CHO
      cell line. For protocol optimization, four CHO miRNAs (cgr-miR-17, cgr-miR-221,
      cgr-miR-21, and cgr-miR-210) were cloned into small hairpin vectors including a
      GFP cassette and transfected. After transfection cells were analyzed for growth
      and productivity over a 4-day period. Even from this small set of four miRNAs,
      the overexpression of miR-17, one of the members of the oncogenic miR-17-92
      cluster, gave proof of principle that this method enables the identification of
      miRNA engineering candidates as its overexpression increased the speed of cell
      proliferation without negatively impacting specific productivity. The here
      presented method is applicable for medium-throughput screening for microRNA, miR
      sponge, siRNA, or mRNA overexpression along with detailed functional
      characterization using the same experimental set up. As the same procedure can be
      applied to different production cell lines, the protocol can also be used to test
      for individual, cell line specific responses to microRNAs. Thus our system
      represents a general platform to functionally screen candidates for rational cell
      factory design.

PMID- 22407746
TI  - (1) H NMR Spectra. Part 28: Proton chemical shifts and couplings in three
      membered rings. A ring current model for cyclopropane and a novel dihedral angle
      dependence for (3) J(HH) couplings involving the epoxy proton.
AB  - The (1) H chemical shifts of selected three-membered ring compounds in CDCl(3)
      solvent were obtained. This allowed the determination of the substituent chemical
      shifts of the substituents in the three-membered rings and the long-range effect
      of these rings on the distant protons. The substituent chemical shifts of common
      substituents in the cyclopropane ring differ considerably from the same
      substituents in acyclic fragments and in cyclohexane and were modelled in terms
      of a three-bond (gamma)-effect. For long-range protons (more than three bonds
      removed), the substituent effects of the cyclopropane ring were analysed in terms
      of the cyclopropane magnetic anisotropy and steric effect. The cyclopropane
      magnetic anisotropy (ring current) shift was modelled by (a) a single equivalent
      dipole perpendicular to and at the centre of the cyclopropane ring and (b) by
      three identical equivalent dipoles perpendicular to the ring placed at each
      carbon atom. Model (b) gave a more accurate description of the (1) H chemical
      shifts and was the selected model. After parameterization, the overall root mean
      square error for the dataset of 289 entries was 0.068 ppm. The anisotropic
      effects are significant for the cyclopropane protons (ca 1 ppm) but decrease
      rapidly with distance. The heterocyclic rings of oxirane, thiirane and aziridine
      do not possess a ring current. (3) J(HH) couplings of the epoxy ring proton with
      side-chain protons were obtained and shown to be dependent on both the H-C-C-H
      and H-C-C-O orientations. Both density functional theory calculations and a
      simple Karplus-type equation gave general agreement with the observed couplings
      (root mean square error 0.5 Hz over a 10-Hz range).

PMID- 22407747
TI  - New oral anticoagulants: a view from the laboratory.
AB  - The new oral anticoagulants are rapidly replacing warfarin for several
      indications. In contrast to warfarin, which lowers the functional levels of all
      of the vitamin K-dependent clotting factors, the new agents target either factor
      Xa or thrombin. With targeted inhibition of coagulation, the new oral
      anticoagulants have pharmacological, biochemical, and clinical features distinct
      from those of warfarin. Focusing on laboratory perspectives, this article
      compares and contrasts the pharmacological and biochemical properties of the new
      oral anticoagulants with those of warfarin and uses this information to speculate
      on the underlying mechanisms responsible for the clinical features that
      differentiate the new agents from warfarin.

PMID- 22407748
TI  - Fetal organ weight estimation by postmortem high-field magnetic resonance imaging
      before 20 weeks' gestation.
AB  - OBJECTIVE: To ascertain whether high-field magnetic resonance imaging (MRI)
      allows accurate estimation of the weight of various fetal organs at postmortem
      before 20 weeks' gestation. METHODS: From 23 fetuses at 9-20 weeks, following
      termination of pregnancy or in-utero fetal death (IUFD), 207 assorted fetal
      organs were evaluated by high-field MRI at 9.4 T prior to conventional autopsy.
      Fetal organ density was calculated by correlating volume and weight at autopsy
      using linear regression analysis, and this was used to estimate fetal organ
      weight by MRI. The relative error in MRI estimation of organ weight was
      calculated as follows: (|MRI weight - autopsy weight|/autopsy weight) * 100 (%).
      Multiple regression analysis was used to investigate the effect on the relative
      error of MRI organ weight estimates of gestational age at TOP or delivery
      following IUFD, autopsy weight, fetal organ examined, IUFD and fetal maceration.
      RESULTS: Of the 207 organs evaluated, 133 (64%) were examined for fetal organ
      density and 155 (75%) for fetal organ weight. Fifty-two organs were excluded from
      our analysis; 41 of these were from fetuses with IUFD, with 39 organs macerated.
      In 32 cases, exclusion was due to an inability to assess the organ both on MRI
      and on conventional autopsy. Volume and weight at autopsy correlated
      significantly, following the linear equation: autopsy volume = (0.9947 * autopsy
      weight) - 4.7556, where autopsy volume is in mm(3) and weight is in mg (r = 0.99,
      P < 0.001). Overall the mean relative error in the MRI estimation of organ weight
      was 68%. Multiple regression analysis showed that the relative error in the MRI
      estimation of organ weight was significantly associated with gestational age at
      TOP or delivery following IUFD and fetal maceration, but not with autopsy weight,
      fetal organ examined or IUFD. In the subgroup of non-macerated organs and for
      fetuses above 14 weeks' gestation, the mean relative error in the MRI estimation
      of organ weight was 34%. CONCLUSION: In fetuses before 20 weeks' gestation,
      noninvasive estimation of organ weight is feasible using high-field MRI, but
      there is a mean overestimation. Limitations of the technique occur mainly in
      cases of small macerated fetuses before 14 weeks' gestation.

PMID- 22407749
TI  - Disease-specific phenotypes in dopamine neurons from human iPS-based models of
      genetic and sporadic Parkinson's disease.
AB  - Induced pluripotent stem cells (iPSC) offer an unprecedented opportunity to model
      human disease in relevant cell types, but it is unclear whether they could
      successfully model age-related diseases such as Parkinson's disease (PD). Here,
      we generated iPSC lines from seven patients with idiopathic PD (ID-PD), four
      patients with familial PD associated to the G2019S mutation in the Leucine-Rich
      Repeat Kinase 2 (LRRK2) gene (LRRK2-PD) and four age- and sex-matched healthy
      individuals (Ctrl). Over long-time culture, dopaminergic neurons (DAn)
      differentiated from either ID-PD- or LRRK2-PD-iPSC showed morphological
      alterations, including reduced numbers of neurites and neurite arborization, as
      well as accumulation of autophagic vacuoles, which were not evident in DAn
      differentiated from Ctrl-iPSC. Further induction of autophagy and/or inhibition
      of lysosomal proteolysis greatly exacerbated the DAn morphological alterations,
      indicating autophagic compromise in DAn from ID-PD- and LRRK2-PD-iPSC, which we
      demonstrate occurs at the level of autophagosome clearance. Our study provides an
      iPSC-based in vitro model that captures the patients' genetic complexity and
      allows investigation of the pathogenesis of both sporadic and familial PD cases
      in a disease-relevant cell type.

PMID- 22407750
TI  - Graphene-CdS nanocomposites: facile one-step synthesis and enhanced
      photoelectrochemical cytosensing.
AB  - Graphene-CdS (GR-CdS) nanocomposites were prepared in a one-step synthesis in
      aqueous solution. The synthetic approach was simple and fast, and it may be
      extended for the synthesis of other GR-metal-sulfide nanocomposites. The as
      prepared GR-CdS nanocomposite films inherited the excellent electron-transport
      properties of GR. In addition, the heteronanostructure of the GR-CdS
      nanocomposites facilitated the spatial separation of the charge carriers, thus
      resulting in enhanced photocurrent intensity, which makes it a promising
      candidate for photoelectrochemical applications. This strategy was used for the
      fabrication of an advanced photoelectrochemical cytosensor, based on these GR-CdS
      nanocomposites, by using a layer-by-layer assembly process. This
      photoelectrochemical cytosensor showed a good photoelectronic effect and cell
      capture ability, and had a wide linear range and low detection limit for Hela
      cells. The as-synthesized GR-CdS nanocomposites exhibited obviously enhanced
      photovoltaic properties, which could be an efficient platform for many other high
      performance photovoltaic devices.

PMID- 22407751
TI  - Engineering the atomic structure of carbon nanotubes by a focused electron beam:
      new morphologies at the sub-nanometer scale.
AB  - Carbon atoms are displaced in pre-selected locations of carbon nanotubes by using
      a focused electron beam in a scanning transmission electron microscope. Sub
      nanometer-sized holes are created that change the morphology of double and triple
      walled carbon nanotubes and connect the shells in a unique way. By combining in
      situ transmission electron microscopy experiments with atomistic simulations, we
      study the bonding between defective shells in the new structures which are
      reminiscent of the shape of a flute. We demonstrate that in double-walled
      nanotubes the shells locally merge by forming nanoarches while atoms with
      dangling bonds can be preserved in triple-walled carbon nanotubes. In the latter
      system, nanoarches are formed between the inner- and outermost shells, shielding
      small graphenic islands with open edges between the neighboring shells. Our
      results indicate that arrays of quantum dots may be produced in carbon nanotubes
      by spatially localized electron irradiation, generating atoms with dangling bonds
      that may give rise to localized magnetic moments.

PMID- 22407752
TI  - The gut-liver axis: a busy two-way street.

PMID- 22407753
TI  - Serum DNA methylation for monitoring response to neoadjuvant chemotherapy in
      breast cancer patients.
AB  - Patients with large or nonoperable breast cancers often receive neoadjuvant
      chemotherapy to facilitate full resection of the tumor and enable conservation of
      the breast. However, currently available methods for evaluation of response
      during therapy are limited and the actual effect of the treatment is only
      recognized at surgery upon completion of chemotherapy. Timely assessment of
      response could allow individual tailoring of the treatment and save noneffective
      drugs and unnecessary toxicity. Here, we suggest that tumor derived DNA
      methylation in the serum may reflect changes in tumor burden and allow early
      recognition of responders versus nonresponders. In this pilot study, we collected
      7 consecutive serum samples from 52 patients with locally advanced breast cancer
      during neoadjuvant chemotherapy. We selected RASSF1, which was methylated in more
      than 80% of the tumors, for serum analysis. Using the "methylation sensitive PCR
      and high resolution melting," we detected RASSF1 methylation in the serum of 21
      patients prior to therapy. In four patients who achieved complete pathological
      response, RASSF1 methylation in the serum became undetectable early during
      therapy. In contrast, in 17 patients that had partial or minimal pathological
      response, serum RASSF1 methylation persisted longer or throughout the treatment
      (complete versus partial response p = 0.02). These findings support further
      development of this assay for monitoring response during neoadjuvant therapy.

PMID- 22407754
TI  - Neurodevelopmental features in 2q23.1 microdeletion syndrome: report of a new
      patient with intractable seizures and review of literature.
AB  - 2q23.1 microdeletion syndrome is a recently characterized chromosomal aberration
      disorder uncovered through array comparative genomic hybridization (array CGH).
      Although the cardinal feature is intellectual disability (ID), neurodevelopmental
      features of the syndrome have not been systematically reviewed. We present a 5
      year-old boy with severe psychomotor developmental delay/ID, progressive
      microcephaly with brain atrophy, growth retardation, and several external
      anomalies. He manifested intractable epilepsy, effectively treated with combined
      antiepileptic drug therapy including topiramate. Array CGH demonstrated a de novo
      interstitial deletion of approximately 1 Mb at 2q23.1-q23.2, involving four genes
      including MBD5. Nineteen patients have been reported to have the syndrome,
      including present patient. All patients whose data were available had ID, 17
      patients (89%) had seizures, and microcephaly was evident in 9 of 18 patients
      (50%). Deletion sizes ranged from 200 kb to 5.5 Mb, comprising 1-15 genes. MBD5,
      the only gene deleted in all patients, is considered to be responsible for ID and
      epilepsy. Furthermore, the deletion junction was sequenced for the first time in
      a patient with the syndrome; and homology of three nucleotides, identified at the
      distal and proximal breakpoints, suggested that the deletion might have been
      mediated by recently-delineated genomic rearrangement mechanism Fork Stalling and
      Template Switching (FoSTeS)/microhomology-mediated break-induced replication
      (MMBIR).

PMID- 22407755
TI  - Xanthohumol induces different cytotoxicity and apoptotic pathways in malignant
      and normal astrocytes.
AB  - Cytotoxicity and the mechanisms of cell death induced by xanthohumol (XN) were
      compared in normal and cancerous human cells as the differences may be relevant
      for the potential use of XN in cancer therapy. The cancer cells seemed to be more
      susceptible to the cytotoxicity of XN than normal cells, but a significant
      difference was observed only in astrocytic cells. XN induced a higher rate of
      apoptosis in glioblastoma cells than in normal astrocytes, which was associated
      with activation of p53 and an elevated Bax/Bcl-2 ratio in glioblastoma cells,
      indicating an intrinsic caspase-dependent apoptotic pathway. In contrast, a
      reduced Bax/Bcl-2 ratio was observed in normal human astrocytes. This was also
      associated with higher expression of the cell cycle inhibitor, p21, in
      glioblastoma cells than in normal astrocytes. In addition, at a lower, non
      cytotoxic concentration, XN partially inhibited the invasiveness of glioblastoma
      cells. Due to the selective sensitivity of astrocytic cells to XN, this compound
      should be studied further as a candidate for adjuvant therapy in the treatment of
      glioma.

PMID- 22407756
TI  - Efficacy of in-office bleaching techniques combined with the application of a
      casein phosphopeptide-amorphous calcium phosphate paste at different moments and
      its influence on enamel surface properties.
AB  - OBJECTIVES: The aim of this in vitro study was to investigate the efficacy of in
      office bleaching technique combined with the application of a casein
      phosphopeptide-amorphous calcium phosphate (CPP-ACP) paste (MI Paste-MI) at
      different moments and its influence on enamel surface properties. METHODS: Eighty
      bovine dental crowns were randomly allocated into eight groups (n = 10), and
      bleached with either 35% hydrogen peroxide (HP) or 37% carbamide peroxide (CP).
      Four different protocols of application of MI were considered: without MI, MI
      applied before bleaching, MI applied after bleaching, and MI applied both before
      and after bleaching. Bleaching effectiveness was measured by the VITA EasyShade
      spectrophotometer utilizing the CIEL*a*b* system (DeltaE, DeltaL*, Deltaa*, and
      Deltab*). Color readings were measured at baseline, 7, 14, and 21 days. Hardness
      and roughness were measured at baseline (T0) and immediately after bleaching
      (T14). Data were subjected to the two-way ANOVA for repeated measurements and
      Tukey's test at 5%. RESULTS: HP groups achieved the greatest color change. The
      application of a CPP-ACP paste did not reduce the efficacy of bleaching
      peroxides. Samples bleached with CP showed decreased hardness at T14. Samples
      bleached with HP that received the application of MI before and before/after
      bleaching did not present hardness decrease at T14. Samples bleached with
      peroxides only and received MI after bleaching showed increased roughness at T14.
      CONCLUSIONS: The use of CPP-ACP was able to prevent negative changes in roughness
      and hardness of bovine enamel when associated to hydrogen peroxide, and might be
      applied before/after the bleaching protocol.

PMID- 22407758
TI  - Effect of light intensity on algal biomass accumulation and biodiesel production
      for mixotrophic strains Chlorella kessleri and Chlorella protothecoide cultivated
      in highly concentrated municipal wastewater.
AB  - In this research, the effect of light intensity on biomass accumulation,
      wastewater nutrient removal through algae cultivation, and biodiesel productivity
      was investigated with algae species Chlorella kessleri and Chlorella
      protothecoide. The light intensities studied were 0, 15, 30, 60, 120, and 200
      umol m(-2) s(-1). The results showed that light intensity had profound impact on
      tested responses for both strains, and the dependence of these responses on light
      intensity varied with different algae strains. For C. kessleri, the optimum light
      intensity was 120 umol m(-2) S(-1) for all responses except for COD removal. For
      C. protothecoide, the optimum light intensity was 30 umol m(-2) S(-1). The major
      components of the biodiesel produced from algae biomass were 16-C and 18-C FAME,
      and the highest biodiesel contents were 24.19% and 19.48% of dried biomass for C.
      kessleri and C. protothecoide, respectively. Both species were capable of
      wastewater nutrients removal under all lighting conditions with high removal
      efficiencies.

PMID- 22407757
TI  - Naloxone can act as an analgesic agent without measurable chronic side effects in
      mice with a mutant mu-opioid receptor expressed in different sites of pain
      pathway.
AB  - Midbrain periaqueductal gray (PAG) and spinal cord dorsal horn are major action
      sites of opioid analgesics in the pain pathway. Our previous study has shown that
      opioid antagonists activate MORS196A-CSTA (a mutant of mu-opioid receptor) as
      full agonists in vitro cell models and naloxone showed antinociceptive effects
      after the expression of MORS196A-CSTA in the spinal cord in mice. The purpose of
      this study is to investigate the site-directed antinociceptive effects of
      naloxone in mice injected with dsAAV-MORS196A-CSTA-EGFP at spinal cord or at
      periaqueductal gray. MORS196A-CSTA-EGFP was administered to ICR mice using dsAAV
      as vector. We measured MORS196A-CSTA-EGFP expression by detecting the EGFP
      visualization with a fluorescence microscope. The antinociceptive effect of
      naloxone was determined by tail-flick test and hot plate test. Drug rewarding
      effect was evaluated by the conditioned place preference test. Naloxone (10
      mg/kg, s.c.) elicited both supraspinal and spinal antinociceptive responses in
      mice injected with the virus at PAG while only spinal antinociceptive response
      was observed in mice injected with virus at dorsal horn region. Chronic naloxone
      treatment did not induce physical dependence or rewarding effect in mice injected
      with MORS196A-CSTA-EGFP in spinal cord or PAG. These data suggest that the
      observed naloxone-induced antinociceptive response is the consequence of the
      local expression of MORS196A-CSTA at specific sites of pain pathway. Injection of
      such MOR mutant and the systemic administration of naloxone can be a new strategy
      in the management of chronic pain without the various side effects associated
      with the use of morphine.

PMID- 22407759
TI  - Impact of concomitant anterior vaginal reconstructive surgery on transobturator
      suburethral tape procedures.
AB  - OBJECTIVE: To explore the functional and morphological impact of concomitant
      anterior vaginal reconstructive surgery on outcome of transobturator suburethral
      tape (TOT) procedures. METHODS: This was a retrospective review and analysis of
      data from 196 women who had undergone a TOT procedure with or without concomitant
      anterior vaginal reconstructive surgery during a 30-month period. Retrieved data
      included clinical information and ultrasound findings. Ultrasound examinations
      assessed the tape location and tape tension at rest, on straining and during
      coughing. Ultrasound parameters representing tape location comprised the sagittal
      tape-symphysis pubis distance, sagittal tape-symphysis pubis angle and tape
      percentile (an indication of tape position along the urethra with respect to
      urethral length); those representing tape tension included urethral encroachment,
      sagittal tape-urethra distances at the upper end, central point and lower end of
      the tape and axial urethral central echolucent area at the center of the tape.
      RESULTS: Of the 196 women, 117 had undergone a TOT procedure without concomitant
      anterior vaginal surgery (Group 1), 44 had undergone TOT placement with anterior
      colporrhaphy (Group 2) and 35 had undergone TOT placement with a transobturator
      vaginal mesh procedure (Group 3). At the 3-month follow-up, functional outcomes
      as well as resting and dynamic ultrasound findings were similar between women
      following TOT procedures without (Group 1) and with (Groups 2 and 3) concomitant
      anterior vaginal surgery. However, a significantly higher rate of urethral
      encroachment at rest was noted in Group 2. CONCLUSIONS: Concomitant anterior
      vaginal reconstructive surgery neither aggravates the functional outcome nor
      affects the ultrasound findings of TOT procedures.

PMID- 22407760
TI  - Secondary hyperparathyroidism but stable bone-mineral density in patients with
      chronic myeloid leukemia treated with imatinib.
AB  - Imatinib is currently the standard treatment for chronic myeloid leukemia(CML).
      Previous studies have shown that imatinib affects bone metabolism in CML
      patients. However, these effects are not well-studied prospectively. The authors
      studied bone-mineral density (BMD) and bone metabolism in 17 CML patients and
      matched controls in 2007 and now repeated the analyses prospectively in 2011. All
      CML patients were in complete cytogenetic remission during this 4-year period and
      treated with 400 mg imatinib q.d. (n 5 15) or 600 mg imatinib q.d. (n 5 2). Mean
      treatment duration was 102 months (range 69-129) in 2011. The authors found that
      serum levels of parathyroid hormone increased significantly in the patients
      between 2007 and 2011, and seven out of 17 patients had secondary
      hyperparathyroidism in 2011. However, the mean areal and volumetric BMDs were
      stable in the CML patients over the 4-year-observation period. Moreover, the CML
      patients had significantly higher volumetric BMD in the cortical compartment when
      compared with controls in 2011 and 2007. Thus, despite a high incidence of
      secondary hyperparathyroidism,there were no signs of osteoporosis or osteomalacia
      in imatinib-treated CML patients as suggested earlier.

PMID- 22407761
TI  - A DFT and TD-DFT approach to the understanding of statistical kinetics in
      substitution reactions of M3Q4 (M = Mo, W; Q = S, Se) cuboidal clusters.
AB  - For many years it has been known that the nine water molecules in
      [M(3)Q(4)(H(2)O)(9)](4+) cuboidal clusters (M = Mo, W; Q = S, Se) can be replaced
      by entering ligands, such as chloride or thiocyanate, and kinetic studies carried
      out mainly on the substitution of the first water molecule at each metal centre
      reveal that the reaction at the three metal centres occurs with statistical
      kinetics; that is, a single exponential with a rate constant corresponding to the
      reaction at the third centre is observed instead of the expected three
      exponential kinetic trace. Such simplification of the kinetic equations requires
      the simultaneous fulfilment of two conditions: first that the three consecutive
      rate constants are in statistical ratio, and second that the metal centres behave
      as independent chromophores. The validity of those simplifications has been
      checked for the case of the reaction of [Mo(3)S(4)(H(2)O)(9)](4+) with Cl(-) by
      using DFT and TD-DFT theoretical calculations. The results of those calculations
      are in agreement with the available experimental information, which indicates
      that the H(2)O ligands trans to the MU-S undergo substitution much faster than
      those trans to the MU(3)-S. Moreover, the energy barriers for the substitution of
      the first water molecule at the three metal centres are close to each other, the
      differences being compatible with the small changes in the numerical values of
      the rate constants required for observation of statistical kinetics. TD-DFT
      calculations lead to calculated electronic spectra, which are in reasonable
      agreement with those experimentally measured, but the calculations do not
      indicate that the three metal centres behave as independent chromophores,
      although the mathematical conditions required for simplification of the kinetic
      traces to a single exponential are reasonably well fulfilled at certain
      wavelengths. A re-examination of the kinetics of the reaction by using global
      fitting procedures yields results, which are compatible with statistical
      kinetics, although an alternative interpretation in which substitution only
      occurs at a single metal centre under reversible conditions is also possible.

PMID- 22407762
TI  - Identification of informative metabolic responses using a minibioreactor: a small
      step change in the glucose supply rate creates a large metabolic response in
      Saccharomyces cerevisiae.
AB  - In this study, a previously developed mini-bioreactor, the Biocurve, was used to
      identify an informative stimulus-response experiment. The identified stimulus
      response experiment was a modest 50% shift-up in glucose uptake rate (qGLC) that
      unexpectedly resulted in a disproportionate transient metabolic response. The 50%
      shift-up in qGLC in the Biocurve resulted in a near tripling of the online
      measured oxygen uptake (qO2) and carbon dioxide production (qCO2) rates,
      suggesting a considerable mobilization of glycogen and trehalose. The 50% shift
      up in qGLC was subsequently studied in detail in a conventional bioreactor (4 l
      working volume), which confirmed the results obtained with the Biocurve.
      Especially relevant is the observation that the 50% increase in glucose uptake
      rate led to a three-fold increase in glycolytic flux, due to mobilization of
      storage materials. This explains the unexpected ethanol and acetate secretion
      after the shift-up, in spite of the fact that after the shift-up the qGLC was far
      less than the critical value. Moreover, these results show that the correct in
      vivo fluxes in glucose pulse experiments cannot be obtained from the uptake and
      secretion rates only. Instead, the storage fluxes must also be accurately
      quantified. Finally, we speculate on the possible role that the transient
      increase in dissolved CO2 immediately after the 50% shift-up in qGLC could have
      played a part in triggering glycogen and trehalose mobilization.

PMID- 22407763
TI  - Incidence and risk factors for breast cancer subtypes in three distinct South
      East Asian ethnic groups: Chinese, Malay and natives of Sarawak, Malaysia.
AB  - We determined the incidences of the estrogen receptor (ER), progesterone receptor
      (PR) and human epidermal growth factor receptor 2 (HER2) subtypes among breast
      cancer cases in Sarawak, Malaysia and their correlation with various risk factors
      in the three ethnic groups: Chinese, Malay and native. Subtype status was
      ascertained for 1,034 cases of female breast cancer (93% of all cases diagnosed
      since 2003), and the age-standardized incidence rates (ASRs) of each subtype were
      inferred. Case-case comparisons across subtypes were performed for reproductive
      risk factors. We found 48% luminal A (ER+/PR+/HER2-), 29% triple-negative (ER-/PR
      /HER2-), 12% triple-positive (ER+/PR+/HER2+) and 11% HER2-overexpressing (ER-/PR
      /HER2+) subtypes, with ASRs of 10.6, 6.0, 2.8 and 2.8 per 100,000, respectively.
      The proportions of subtypes and ASRs differed significantly by ethnic groups:
      HER2-positive cases were more frequent in Malays (29%; 95% CI [23;35]) than
      Chinese (22%; [19;26] and natives (21%; [16;26]); triple-negative cases were less
      frequent among Chinese (23%; [20;27]) than Malays (33%; [27;39]) and natives
      (37%; [31;43]). The results of the case-case comparison were in accordance with
      those observed in western case series. Some uncommon associations, such as
      between triple-negative subtype and older age at menopause (OR, 1.59; p < 0.05),
      were found. The triple-negative and HER2+ subtypes predominate in our region,
      with significant differences among ethnic groups. Our results support the idea
      that the risk factors for different subtypes vary markedly. Westernized
      populations are more likely to have factors that increase the risk for the
      luminal A type, while risk factors for the triple-negative type are more frequent
      in local populations.

PMID- 22407765
TI  - Cholangiocarcinoma: a cancer in search of the right classification.

PMID- 22407764
TI  - The tumour suppressor and chromatin-remodelling factor BRG1 antagonizes Myc
      activity and promotes cell differentiation in human cancer.
AB  - BRG1, a member of the SWI/SNF complex, is mutated in cancer, but it is unclear
      how it promotes tumourigenesis. We report that re-expression of BRG1 in lung
      cancer cells up-regulates lung-specific transcripts, restoring the gene
      expression signature of normal lung. Using cell lines from several cancer types
      we found that those lacking BRG1 do not respond to retinoic acid (RA) or
      glucocorticoids (GC), while restoration of BRG1 restores sensitivity. Conversely,
      in SH-SY5Y cells, a paradigm of RA-dependent differentiation, abrogation of BRG1
      prevented the response to RA. Further, our data suggest an antagonistic
      functional connection between BRG1 and MYC, whereby, refractoriness to RA and GC
      by BRG1 inactivation involves deregulation of MYC activity. Mechanistically, some
      of these effects are mediated by BRG1 binding to MYC and MYC-target promoters.
      The BRG1-MYC antagonism was also evident in primary tumours. Finally, BRG1
      restoration significantly dampened invasion and progression and decreased MYC in
      lung cancer cells orthotopically implanted in nude mice. Thus, BRG1 inactivation
      enables cancer cells to sustain undifferentiated gene expression programs and
      prevent its response to environmental stimuli.

PMID- 22407766
TI  - Facile preparation of Ag2S/Ag semiconductor/metal heteronanostructures with
      remarkable antibacterial properties.

PMID- 22407768
TI  - Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its
      nucleolar localization.
AB  - CIGB-300 is a novel anticancer peptide that impairs the casein kinase 2-mediated
      phosphorylation by direct binding to the conserved phosphoacceptor site on their
      substrates. Previous findings indicated that CIGB-300 inhibits tumor cell
      proliferation in vitro and induces tumor growth delay in vivo in cancer animal
      models. Interestingly, we had previously demonstrated that the putative oncogene
      B23/nucleophosmin (NPM) is the major intracellular target for CIGB-300 in a
      sensitive human lung cancer cell line. However, the ability of this peptide to
      target B23/NPM in cancer cells with differential CIGB-300 response phenotype
      remained to be determined. Interestingly, in this work, we evidenced that CIGB
      300's antiproliferative activity on tumor cells strongly correlates with its
      nucleolar localization, the main subcellular localization of the previously
      identified B23/NPM target. Likewise, using CIGB-300 equipotent doses
      (concentration that inhibits 50% of proliferation), we demonstrated that this
      peptide interacts and inhibits B23/NPM phosphorylation in different cancer cell
      lines as evidenced by in vivo pull-down and metabolic labeling experiments.
      Moreover, such inhibition was followed by a fast apoptosis on CIGB-300-treated
      cells and also an impairment of cell cycle progression mainly after 5 h of
      treatment. Altogether, our data not only validates B23/NPM as a main target for
      CIGB-300 in cancer cells but also provides the first experimental clues to
      explain their differential antiproliferative response. Importantly, our findings
      suggest that further improvements to this cell penetrating peptide-based drug
      should entail its more efficient intracellular delivery at such subcellular
      localization.

PMID- 22407767
TI  - Subtelomeric 6.7 Mb trisomy 10p and 5.6 Mb monosomy 21q detected by FISH and
      array-CGH in three related patients.
AB  - Cryptic subtelomeric chromosomal aberrations are responsible for 5-10% of
      moderate/severe and 1% of mild intellectual disability. Unbalanced subtelomeric
      chromosomal rearrangements result in variable phenotypes which seem to be highly
      influenced by both the size of the duplication/deletion and the chromosomes
      involved in the translocation. We report on three related patients with moderate
      intellectual disability, language delay, hypotonia, facial dysmorphism, cardiac
      anomalies, scoliosis, and kyphosis in whom a familial (maternal) unbalanced
      submicroscopic translocation was found by subtelomeric fluorescence in situ
      hybridization (FISH). This rearrangement resulted in a partial trisomy 10pter and
      partial monosomy 21qter. The karyotype was 46,XY.ish der(21)t(10;21)(p14;q22.2).
      Confirmation of a 6.7 Mb size distal duplication of the p15.3-14 region of
      chromosome 10 and a 5.6 Mb distal deletion of the q22.2-22.3 region of chromosome
      21 was obtained by array-CGH. To our best knowledge, such a composition of
      subtelomeric unbalanced translocations has not yet been published. Detection of
      this aberration in successive pregnancies of carrier members of the family by
      prenatal FISH could prevent the recurrence of the disease. Furthermore, detection
      of the rearrangements and identification of genes located in the chromosomal
      regions involved might be of interest.

PMID- 22407769
TI  - Inhibitory effects of key compounds isolated from Corni fructus on BACE1
      Activity.
AB  - Progressive cerebral deposition of Abeta in the brain is a seminal event in the
      pathogenesis of Alzheimer's disease (AD). Abeta is generated from the amyloid
      precursor protein (APP) by proteolytic processing of beta-secretase (BACE1) and
      gamma-secretase. Consequently, BACE1, a key enzyme in the production of Abeta, is
      a prime target for therapeutic intervention in AD. In the course of screening for
      natural BACE1 inhibitors from Corni fructus, the ethyl acetate (EtOAc) fraction
      showed significant inhibitory activity against BACE1. By activity guided
      purification, three compounds of BACE1 inhibitors p-coumaric acid, gallic acid
      and ursolic acid were isolated from Corni fructus EtOAc fraction. All isolated
      compounds suppressed BACE1 in a dose dependent manner. p-Coumaric acid, in
      particular, exhibited significant inhibitory activity against BACE1 with 9.0 *
      10(-5)  m and a K(i) value of 1.9 * 10(-6)  m. Also this compound was non
      competitive with a substrate in the Dixon plot, suggesting that it might bind
      either to the beta-secretase subsite or to another regulatory site. All compounds
      showed no significant attenuation of TACE (alpha-secretase) and other serine
      proteases such as chymotrypsin and trypsin, demonstrating that they were
      relatively selective and specific inhibitors of BACE1. These novel findings
      suggest that Corni fructus contains biologically active components that may be
      used to attenuate the progression and/or prevention of Alzheimer's disease.

PMID- 22407770
TI  - Self-cycling operation increases productivity of recombinant protein in
      Escherichia coli.
AB  - Self-cycling fermentation (SCF), a cyclical, semi-continuous process that induces
      cell synchrony, was incorporated into a recombinant protein production scheme.
      Escherichia coli CY15050, a lac(-) mutant lysogenized with temperature-sensitive
      phage lambda modified to over-express beta-galactosidase, was used as a model
      system. The production scheme was divided into two de-coupled stages. The host
      cells were cultured under SCF operation in the first stage before being brought
      to a second stage where protein production was induced. In the first stage, the
      host strain demonstrated a stable cycling pattern immediately following the first
      cycle. This reproducible pattern was maintained over the course of the
      experiments and a significant degree of cell synchrony was obtained. By growing
      cells using SCF, productivity increased 50% and production time decreased by 40%
      compared to a batch culture under similar conditions. In addition, synchronized
      cultures induced from the end of a SCF cycle displayed shorter lysis times and a
      more complete culture-wide lysis than unsynchronized cultures. Finally, protein
      synthesis was influenced by the time at which the lytic phase was induced in the
      cell life cycle. For example, induction of a synchronized culture immediately
      prior to cell division resulted in the maximum protein productivity, suggesting
      protein production can be optimized with respect to the cell life cycle using
      SCF.

PMID- 22407771
TI  - Observations and descriptions versus explanations--an example: does nature, does
      theory know about steric hindrance?
AB  - Quantum chemical investigations in the literature sometimes underpin traditional
      chemical concepts (such as those of different primary and secondary types of
      chemical bonding or of steric repulsions) but sometimes also seem to undermine
      them. Conceptual pitfalls in recent discussions in this and other leading
      journals, when combining empirically and quantum chemically based reasoning, can
      be avoided when taking four points into account: 1) The construction of
      theoretical concepts should be guided by both, physical rigor and the aim of
      recovering the notions that have been found chemically fruitful. 2) Partitioning
      of a chemical phenomenon into elementary physical steps should not only consider
      the stationary initial and final states but also include non-stationary
      intermediate states that exhibit the physically characteristic internal
      relaxation mechanism. 3) Even if sufficiently accurate, the partitioning into
      large contributions of opposite sign is less valuable for a qualitative chemical
      understanding, as long as the trend of one big decisive term or sum of terms
      cannot be made obvious (for instance on the basis of the variation principle--or
      by chemical intuition). 4) Causal explanatory notions, even if more vague or
      fuzzy than some more rigorous and unique descriptive concepts, have to be
      advanced towards a more fruitful chemical theory.

PMID- 22407772
TI  - Fibrinogen Sumperk II: dysfibrinogenemia in an individual with two coding
      mutations.
AB  - Fibrinogen-a 340-kDa glycoprotein-plays a crucial role in blood coagulation,
      platelet aggregation, wound healing, and other physiological processes. A
      mutation in fibrinogen may lead to congenital dysfibrinogenemia,a rare disease
      characterized by the functional deficiency of fibrinogen. About 580 cases of
      abnormal fibrinogens have been reported worldwide; thereof 335 cases in the
      fibrinogen Aa chain[1]. To our knowledge, only five cases of abnormal fibrinogens
      with two mutations [2-6] and one case of two different mutations in the same
      family [7] have been described earlier. A 52-year-old female was examined for
      bleeding. Routine hemostasis screening resulted in a diagnosis of
      dysfibrinogenemia. Functional testing revealed prolonged fibrin polymerization,
      prolonged lysis of the clot, abnormal fibrin morphology,and fibrinopeptides
      release. Genetic analysis showed two heterozygous nonsense mutations-previously
      described mutation AaGly13Glu and a novel mutation Aa Ser314Cys. The mutation Aa
      Gly13-Glu was found in her brother and niece, but there was no evidence in either
      of the mutation Aa Ser314Cys. While mutation Aa Gly13Glu is responsible for
      abnormal fibrinopeptide release and prolonged thrombin time, the novel mutation
      Aa Ser314Cys seems to affect fibrin morphology and fibrinolysis.

PMID- 22407773
TI  - Misexpression of Dickkopf-1 in endothelial cells, but not in chondrocytes or
      hypertrophic chondrocytes, causes defects in endochondral ossification.
AB  - Developing cartilage serves as a template for long-bone development during
      endochondral ossification. Although the coupling of cartilage and bone
      development with angiogenesis is an important regulatory step for endochondral
      ossification, the molecular mechanisms are poorly understood. One possible
      mechanism involves the action of Dickkopf (DKK), which is a family of soluble
      canonical Wnt antagonists with four members (DKK1-4). We initially observed
      opposite expression patterns of Dkk1 and Dkk2 during angiogenesis and chondrocyte
      differentiation: downregulation of Dkk1 and upregulation of Dkk2. We examined the
      in vivo role of Dkk1 and Dkk2 in linking cartilage/bone development and
      angiogenesis by generating transgenic (TG) mice that specifically express Dkk1 or
      Dkk2 in chondrocytes, hypertrophic chondrocytes, or endothelial cells. Despite
      specific expression pattern during cartilage development, chondrocyte- and
      hypertrophic chondrocyte-specific Dkk1 and Dkk2 TG mice showed normal
      developmental phenotypes. However, Dkk1 misexpression in endothelial cells
      resulted in defects of endochondral ossification and reduced skeletal size. The
      defects are caused by the inhibition of angiogenesis in developing bone and
      subsequent inhibition of apoptosis of hypertrophic chondrocytes and cartilage
      resorption.

PMID- 22407775
TI  - B3N3 borazine substitution in hexa-peri-hexabenzocoronene: computational analysis
      and Scholl reaction of hexaphenylborazine.
AB  - The doping of graphene molecules by borazine (B(3)N(3)) units may modify the
      electronic properties favorably. Therefore, the influence of the substitution of
      the central benzene ring of hexa-peri-hexabenzocoronene (HBC, C(42)H(18)) by an
      isoelectronic B(3)N(3) ring resulting in C(36)B(3)N(3)H(18) (B3N3HBC) is
      investigated by computational methods. For comparison, the isoelectronic and
      isosteric all-B/N molecule B(21)N(21)H(18) (termed BN) and its carbon derivative
      C(6)B(18)N(18)H(18) (C6BN), obtained by substitution of a central B(3)N(3) by a
      C(6) ring, are also studied. The substitution of C(6) in the HBC molecule by a
      B(3)N(3) unit results in a significant change of the computed IR vibrational
      spectrum between 1400 and 1600 cm(-1) due to the polarity of the borazine core.
      The properties of the BN molecule resemble those of hexagonal boron nitride, and
      substitution of the central B(3)N(3) ring by C(6) changes the computed IR
      vibrational spectrum only slightly. The allowed transitions to excited states
      associated with large oscillator strengths shift to higher energy upon going from
      HBC to B3N3HBC, but to lower energy upon going from BN to C6BN. The possibility
      of synthesis of B3N3HBC from hexaphenylborazine (HPB) using the Scholl reaction
      (CuCl(2)/AlCl(3) in CS(2)) is investigated. Rather than the desired B3N3HBC an
      insoluble and X-ray amorphous polymer P is obtained. Its analysis by IR and (11)B
      magic angle spinning NMR spectroscopy reveals the presence of borazine units. The
      changes in the (11)B quadrupolar coupling constant C(Q), asymmetry parameter eta,
      and isotropic chemical shift delta(iso)((11)B) with respect to HPB are in
      agreement with a structural model that includes B3N3HBC-derived monomeric units
      in polymer P. This indicates that both intra- and intermolecular
      cyclodehydrogenation reactions take place during the Scholl reaction of HPB.

PMID- 22407776
TI  - Characteristic patterns of altered DNA methylation predict emergence of human
      hepatocellular carcinoma.
AB  - We aimed to identify the specific subset of tumor suppressor genes (TSGs) that
      are methylation-silenced during the earliest steps of hepatocarcinogenesis, and
      to further evaluate whether these genes can serve as predictive biomarkers of
      hepatocellular carcinoma (HCC) emergence. A total of 482 liver tissues including
      177 pairs of HCCs and matched nontumor livers and 128 liver biopsies from chronic
      hepatitis C (CHC) patients were analyzed for quantitative methylation analysis in
      24 TSG promoters and three MINT loci. The tumors were classified as early, less
      progressed, and highly progressed HCCs using histology and radiological
      approaches. A subset of TSGs that harbored distinctly high levels of methylation
      in early HCCs were selected. Based on the methylation profiles of these genes,
      Kaplan-Meier analyses were performed to determine time-to-HCC occurrence in CHC
      patients. Subsequently, multivariate analysis was performed using age, gender,
      fibrosis stage, and number of methylated TSGs as covariates. Among TSGs analyzed,
      a subset of eight TSGs (HIC1, GSTP1, SOCS1, RASSF1, CDKN2A, APC, RUNX3, and
      PRDM2) demonstrated a distinct cluster by hierarchical clustering and receiver
      operating characteristic analyses. This subset of TSGs showed significantly
      higher methylation levels in the early HCCs (P < 0.0001). In the CHC patients,
      methylation frequencies in these TSGs were associated with shorter time-to-HCC
      occurrence (P < 0.0001), and number of methylated genes was an independent risk
      factor for HCC (hazard ratio = 5.21, 95% confidence interval = 2.25-11.76, P =
      0.0002). CONCLUSION: Epigenetic inactivation of a subset of TSGs plays a critical
      role in the earliest steps of hepatocarcinogenesis. Furthermore, epigenetic
      inactivation of these genes in CHC provides a prognostic value for determining
      the risk for developing HCC later in life.

PMID- 22407777
TI  - Vaccine process technology.
AB  - The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine
      production methods (e.g., in ovo, cell culture) are intimately tied to each
      other. As vaccine technology has advanced, the methods to produce the vaccine
      have advanced and new vaccine opportunities have been created. These technologies
      will continue to evolve as we strive for safer and more immunogenic vaccines and
      as our understanding of biology improves. The evolution of vaccine process
      technology has occurred in parallel to the remarkable growth in the development
      of therapeutic proteins as products; therefore, recent vaccine innovations can
      leverage the progress made in the broader biotechnology industry. Numerous
      important legacy vaccines are still in use today despite their traditional
      manufacturing processes, with further development focusing on improving stability
      (e.g., novel excipients) and updating formulation (e.g., combination vaccines)
      and delivery methods (e.g., skin patches). Modern vaccine development is
      currently exploiting a wide array of novel technologies to create safer and more
      efficacious vaccines including: viral vectors produced in animal cells, virus
      like particles produced in yeast or insect cells, polysaccharide conjugation to
      carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer
      vaccines created by in vitro activation of patient leukocytes. Purification
      advances (e.g., membrane adsorption, precipitation) are increasing efficiency,
      while innovative analytical methods (e.g., microsphere-based multiplex assays,
      RNA microarrays) are improving process understanding. Novel adjuvants such as
      monophosphoryl lipid A, which acts on antigen presenting cell toll-like
      receptors, are expanding the previously conservative list of widely accepted
      vaccine adjuvants. As in other areas of biotechnology, process characterization
      by sophisticated analysis is critical not only to improve yields, but also to
      determine the final product quality. From a regulatory perspective, Quality by
      Design (QbD) and Process Analytical Technology (PAT) are important initiatives
      that can be applied effectively to many types of vaccine processes. Universal
      demand for vaccines requires that a manufacturer plan to supply tens and
      sometimes hundreds of millions of doses per year at low cost. To enable broader
      use, there is intense interest in improving temperature stability to allow for
      excursions from a rigid cold chain supply, especially at the point of
      vaccination. Finally, there is progress in novel routes of delivery to move away
      from the traditional intramuscular injection by syringe approach.

PMID- 22407778
TI  - Microchip capillary gel electrophoresis of multiply PEGylated high-molecular-mass
      glycoproteins.
AB  - PEGylation is the most successful approach, to date, to prolong the in vivo
      survival of recombinant proteins. The conjugation of the polymer to glycoproteins
      results in challenging analysis, and furthermore, requires a wide variety of
      analytical tools for the determination of the extent of PEGylation. Herein, we
      present microchip capillary gel electrophoresis (MCGE) with a non-commercial high
      molecular-weight protein assay for the analysis of the PEGylation degree with a
      focus on multiple PEGylation. To show the potential of the modified MCGE system,
      high-mass PEGylated glycoproteins (e.g. coagulation factor VIII) were analyzed.
      For the von Willebrand factor, the influence of glycans and the hydrodynamic
      radius on migration time and molecular weight determination is shown. The
      modified MCGE assay system is a powerful tool for the rapid assessment of the
      degree of PEGylation, demonstrating conjugate quality or reaction control of
      PEGylated proteins. This is the main advantage over time-consuming conventional
      SDS-PAGE. Furthermore, electrophoretic separation, staining, destaining, and
      fluorescence detection in one step combined with automated data analysis show
      that the MCGE system is a promising technique for high-throughput monitoring. The
      MCGE system can be used for rapid structure confirmation ("MCGE fingerprinting")
      of multiply PEGylated glycoproteins beyond the 230 kDa molecular mass range.

PMID- 22407779
TI  - Neonatal detection of 5p13.2 duplication and delineation of the phenotype.
AB  - A newborn boy with broad forehead, mild microretrognathia, large hands and feet,
      arachnodactyly and a cortical thumb also had left renal agenesis, dysgenesis of
      corpus callosum with psychomotor delay. After olignucleotide array comparative
      genomic hybridization (array-CGH) analysis, we detected a 900 kb duplication in
      cytoband 5p13.2, apperently a first clinical description.

PMID- 22407780
TI  - A randomized, pilot study to assess the efficacy and safety of curcumin in
      patients with active rheumatoid arthritis.
AB  - Curcumin is known to possess potent antiinflammatory and antiarthritic
      properties. This pilot clinical study evaluated the safety and effectiveness of
      curcumin alone, and in combination with diclofenac sodium in patients with active
      rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized
      into three groups with patients receiving curcumin (500 mg) and diclofenac sodium
      (50 mg) alone or their combination. The primary endpoints were reduction in
      Disease Activity Score (DAS) 28. The secondary endpoints included American
      College of Rheumatology (ACR) criteria for reduction in tenderness and swelling
      of joint scores. Patients in all three treatment groups showed statistically
      significant changes in their DAS scores. Interestingly, the curcumin group showed
      the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50
      and 70) and these scores were significantly better than the patients in the
      diclofenac sodium group. More importantly, curcumin treatment was found to be
      safe and did not relate with any adverse events. Our study provides the first
      evidence for the safety and superiority of curcumin treatment in patients with
      active RA, and highlights the need for future large-scale trials to validate
      these findings in patients with RA and other arthritic conditions.

PMID- 22407781
TI  - Sacrificial templating synthesis of hematite nanochains from [Fe18S25](TETAH)14
      nanoribbons: their magnetic, electrochemical, and photocatalytic properties.
AB  - Unique hematite nanochains self-assembled from alpha-Fe(2)O(3) nanoparticles can
      be synthesized by thermal decomposition of [Fe(18)S(25)](TETAH)(14) as an
      appropriate nanoribbon precursor (TETAH = protonated triethylenetetramine).
      Magnetic studies have revealed greatly enhanced coercivity of the 1D hematite
      nanochains compared with that of dispersed alpha-Fe(2)O(3) nanoparticles at low
      temperature, which may be attributed to their increased shape anisotropy and
      magnetocrystalline anisotropy. The photocatalytic properties of the hematite
      nanochains have been studied, as well as their electrochemical properties as
      cathode materials of lithium-ion batteries. The results have shown that both
      properties are dependent on the BET specific surface areas of the 1D hematite
      nanochains.

PMID- 22407782
TI  - The dual role of CXCL8 in human CNS stem cell function: multipotent neural stem
      cell death and oligodendrocyte progenitor cell chemotaxis.
AB  - Research into multiple sclerosis (MS) has shown that cells purportedly important
      to myelin repair within the CNS, namely neural stem cells (NSC) and
      oligodendrocyte progenitor cells (OPC), are recruited to active lesion sites
      during the course of the disease. However, over time these cells appear to become
      depleted or functionally blocked in and around lesions, accompanied by a failure
      of repair mechanisms. We have previously demonstrated elevated CXCL8 in patients
      with MS, and hypothesized that this chemokine may play a role in the pathology of
      this disease. Using NSC and OPC derived in vitro from human embryonic stem cells
      (hESC) we demonstrate here that CXCL8 has a dual role on stem cell biology in
      vitro. CXCL8 caused CXCR1-mediated death of NSC, but not OPC, whilst also acting
      as a potent chemoattractant for both cell types. These data support a context
      dependent role for CXCL8 expression in the CNS in which it may drive recruitment
      of NSC and OPC to sites of inflammation, but as a side-effect could also
      contribute to the failure of myelin repair in MS.

PMID- 22407784
TI  - Fulminant thrombotic microangiopathy in pediatrics: where diagnostic and
      therapeutic dilemmas meet.

PMID- 22407783
TI  - Platelet-derived growth factor-responsive neural precursors give rise to
      myelinating oligodendrocytes after transplantation into the spinal cords of
      contused rats and dysmyelinated mice.
AB  - Spinal cord injury (SCI) results in substantial oligodendrocyte death and
      subsequent demyelination leading to white-matter defects. Cell replacement
      strategies to promote remyelination are under intense investigation; however, the
      optimal cell for transplantation remains to be determined. We previously isolated
      a platelet-derived growth factor (PDGF)-responsive neural precursor (PRP) from
      the ventral forebrain of fetal mice that primarily generates oligodendrocytes,
      but also astrocytes and neurons. Importantly, human PRPs were found to possess a
      greater capacity for oligodendrogenesis than human epidermal growth factor-
      and/or fibroblast growth factor-responsive neural stem cells. Therefore, we
      tested the potential of PRPs isolated from green fluorescent protein (GFP)
      expressing transgenic mice to remyelinate axons in the injured rat spinal cord.
      PRPs were transplanted 1 week after a moderate thoracic (T9) spinal cord
      contusion in adult male rats. After initial losses, PRP numbers remained stable
      from 2 weeks posttransplantation onward and those surviving cells integrated into
      host tissue. Approximately one-third of the surviving cells developed the typical
      branched phenotype of mature oligodendrocytes, expressing the marker APC-CC1. The
      close association of GFP cells with myelin basic protein as well as with Kv1.2
      and Caspr in the paranodal and juxtaparanodal regions of nodes of Ranvier
      indicated that the transplanted cells successfully formed mature myelin sheaths.
      Transplantation of PRPs into dysmyelinated Shiverer mice confirmed the ability of
      PRP-derived cells to produce compact myelin sheaths with normal periodicity.
      These findings indicate that PRPs are a novel candidate for CNS myelin repair,
      although PRP-derived myelinating oligodendrocytes were insufficient to produce
      behavioral improvements in our model of SCI.

PMID- 22407785
TI  - Direct evidence that PKCalpha positively regulates wound re-epithelialization:
      correlation with changes in desmosomal adhesiveness.
AB  - Non-healing wounds cause considerable patient morbidity and represent a
      significant economic burden. Central to wound repair is re-epithelialization, a
      crucial process involving the modulation of cell adhesion to allow keratinocyte
      migration to cover the exposed underlying tissues. The cellular mechanisms
      regulating the earliest stages of re-epithelialization are unclear. We present
      the first direct evidence that protein kinase Calpha (PKCalpha) plays an
      important role in regulating wound re-epithelialization. In PKCalpha(-/-) mice re
      epithelialization is delayed, while in novel bitransgenic mice over-expressing
      constitutively active PKCalpha it is accelerated. These effects are not due to
      changes in keratinocyte proliferation, apoptosis or intrinsic cell motility.
      Instead, they correlate with changes in desmosomal adhesiveness, delay being
      preceded by retained desmosomal hyper-adhesiveness and acceleration with a rapid
      switch to desmosomal Ca(2+) -dependence. We demonstrate mechanistic conservation
      in acute human wounds where PKCalpha localizes to wound edge desmosomes, which
      become Ca(2+) -dependent. However, in chronic wounds PKCalpha remains cytoplasmic
      and desmosomes fail to switch from the hyper-adhesive state. These results throw
      new mechanistic light on the earliest stages of wound re-epithelialization and
      suggest activation of PKCalpha as a new therapeutic strategy for non-healing
      wounds.

PMID- 22407787
TI  - Electrostatics at the origin of the stability of phosphate-phosphate complexes
      locked by hydrogen bonds.
AB  - Stronger than you'd think: Ab initio calculations reveal that hydrogen bonds can
      lock phosphates into stable gas-phase complexes, showing that hydrogen bonding
      can overcome anion-anion repulsion. These complexes present a large energetic
      barrier of dissociation. The stability of the complexes can be explained in terms
      of the electrostatic interaction in the hydrogen-bond region.

PMID- 22407786
TI  - Temporal trends and determinants of longitudinal change in 25-hydroxyvitamin D
      and parathyroid hormone levels.
AB  - Vitamin D is essential for facilitating calcium absorption and preventing
      increases in parathyroid hormone (PTH), which can augment bone resorption. Our
      objectives were to examine serum levels of 25-hydroxyvitamin D [25(OH)D] and PTH,
      and factors related to longitudinal change in a population-based cohort. This is
      the first longitudinal population-based study looking at PTH and 25(OH)D levels.
      We analyzed 3896 blood samples from 1896 women and 829 men in the Canadian
      Multicentre Osteoporosis Study over a 10-year period starting in 1995 to 1997. We
      fit hierarchical models with all available data and adjusted for season. Over 10
      years, vitamin D supplement intake increased by 317 (95% confidence interval [CI]
      277 to 359) IU/day in women and by 193 (135 to 252) IU/day in men. Serum 25(OH)D
      (without adjustment) increased by 9.3 (7.3 to 11.4) nmol/L in women and by 3.5
      (0.6 to 6.4) nmol/L in men but increased by 4.7 (2.4 to 7.0) nmol/L in women and
      by 2.7 (-0.6 to 6.2) nmol/L in men after adjustment for vitamin D supplements.
      The percentage of participants with 25(OH)D levels <50 nmol/L was 29.7% (26.2 to
      33.2) at baseline and 19.8% (18.0 to 21.6) at year 10 follow-up. PTH decreased
      over 10 years by 7.9 (5.4 to 11.3) pg/mL in women and by 4.6 (0.2 to 9.0) pg/mL
      in men. Higher 25(OH)D levels were associated with summer, younger age, lower
      body mass index (BMI), regular physical activity, sun exposure, and higher total
      calcium intake. Lower PTH levels were associated with younger age and higher
      25(OH)D levels in both women and men and with lower BMI and participation in
      regular physical activity in women only. We have observed concurrent increasing
      25(OH)D levels and decreasing PTH levels over 10 years. Secular increases in
      supplemental vitamin D intake influenced both changes in serum 25(OH)D and PTH
      levels.

PMID- 22407788
TI  - Fontimonas thermophila gen. nov., sp. nov., a moderately thermophilic bacterium
      isolated from a freshwater hot spring, and proposal of Solimonadaceae fam. nov.
      to replace Sinobacteraceae Zhou et al. 2008.
AB  - A novel bacterial strain designated HA-01(T) was isolated from a freshwater
      terrestrial hot spring located at Hot Springs National Park, Arkansas, USA. Cells
      were Gram-negative-staining, rod-shaped, aerobic, chemo-organotrophic, oxidase-
      and catalase-positive, non-spore-forming and motile by means of a single polar
      flagellum. Growth occurred at 37-60  degrees C, with an optimum between 45 and 50
      degrees C, and at pH 6.5-8.5, with an optimum between pH 6.5 and 7.0.
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that the closest
      relatives of strain HA-01(T) were Solimonas aquatica NAA-16(T) (93.8 %),
      Solimonas flava CW-KD 4(T) (94.1 %), Solimonas soli DCY12(T) (93.1 %), Solimonas
      variicoloris MN28(T) (94.0 %), Nevskia ramosa Soe1(T) (91.2 %) and
      Hydrocarboniphaga effusa AP103(T) (91.1 %). Major fatty acids consisted of C(16 :
      0), iso-C(16 : 0), C(16 : 1)omega5c and summed feature 8 (C(18 : 1)omega9c, C(18
      : 1)omega7c and C(18 : 1)omega6c). Polar lipids consisted of
      diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine, and
      the major isoprenoid quinone was Q-8. The DNA G+C content was 64.4 mol%. Based on
      phylogenetic, phenotypic and chemotaxonomic evidence, it is proposed that strain
      HA-01(T) represents a novel species in a new genus for which the name Fontimonas
      thermophila gen. nov., sp. nov. is proposed. The type strain of the type species
      is HA-01(T) (= DSM 23609(T) = CCUG 59713(T)). A new family, Solimonadaceae fam.
      nov., is also proposed to replace Sinobacteriaceae Zhou et al. 2008.

PMID- 22407789
TI  - Metschnikowia proteae sp. nov., a nectarivorous insect-associated yeast species
      from Africa.
AB  - A collection of yeasts isolated from nectar of flowers of Protea caffra
      (Proteaceae) and associated scarab beetles (Atrichelaphinis tigrina, Cyrtothyrea
      marginalis, Trichostetha fascicularis and Heterochelus sp.) and drosophilid flies
      in South Africa, contained 28 isolates that could not be assigned to known
      species. Comparisons of the D1/D2 domains of the large subunit rRNA gene
      demonstrated the existence of three separate phylotypes with an affinity to the
      genus Metschnikowia and more specifically to the beetle-associated large-spored
      Metschnikowia clade. Twenty-six strains that had similar D1/D2 sequences were
      mixed in all pairwise combinations. They were found to mate and give rise to
      large asci typical of those in the clade. The name Metschnikowia proteae sp. nov.
      (type strain EBDT1Y1(T) = CBS 12522(T) = NRRL Y-48784(T); allotype strain EBDC2Y2
      = CBS 12521 = NRRL Y-48785) is proposed to accommodate this novel species. The
      ecology of this novel yeast species is discussed in relation to its potential
      plant and insect host species. The additional two single strains isolated from
      Heterochelus sp. represent two novel undescribed species (Candida sp. 1 EBDM2Y3
      and Candida sp. 2 EBDM8Y1). As these single strains are probably haploid mating
      types of Metschnikowia species, their description is deferred until the species
      are sufficiently well sampled to permit meaningful descriptions.

PMID- 22407790
TI  - Budvicia diplopodorum sp. nov. and emended description of the genus Budvicia.
AB  - A Gram-negative, rod-shaped, weakly motile, non-spore-forming bacterium (D9(T))
      was isolated from the gut of Cylindroiulus fulviceps (Diplopoda) on 1/3-strength
      nutrient agar plates. On the basis of 16S rRNA gene sequence similarity, strain
      D9(T) was shown to be phylogenetically closely related to the type strain of
      Budvicia aquatica, the sole species of the genus Budvicia, family
      Enterobacteriaceae. The similarity of the 16S rRNA gene sequences of strain D9(T)
      and B. aquatica DSM 5075(T) was 98.4 %. Other strains that showed high pairwise
      similarities with the isolate belonged to the genus Yersinia: Y. frederiksenii
      ATCC 33641(T) (96.8 % 16S rRNA gene sequence similarity), Y. massiliensis CCUG
      53443(T) (96.8 %), Y. pestis NCTC 5923(T) (96.8 %), Y. pseudotuberculosis ATCC
      29833(T) (96.8 %), Y. similis CCUG 52882(T) (96.7 %) and Y. ruckeri ATCC 29473(T)
      (96.5 %). The similarities of sequences of the housekeeping genes rpoB, hsp60 and
      gyrB between strain D9(T) and B. aquatica DSM 5075(T) and other members of the
      Enterobacteriaceae were less than 94 %. Phylogenetic trees based on all four gene
      sequences unequivocally grouped the isolate with the type strain of B. aquatica
      and separately from the genus Yersinia. Cells contained the quinones Q-8, Q-7 and
      MK-8. The major polar lipids were phosphatidylglycerol and
      phosphatidylethanolamine. The G+C content of the DNA (48.3 mol%) and the whole
      cell fatty acid composition of strain D9(T) (C(14 : 0), C(16 : 1)omega7c, C(16 :
      0), cyclo-C(17 : 0) and C(18 : 1)omega7c as major components) were typical for
      members of the Enterobacteriaceae. DNA-DNA hybridization of strain D9(T) with B.
      aquatica DSM 5075(T) resulted in a relatedness of 30.4 %, indicating that the
      isolate did not belong to B. aquatica. Physiological tests allowed the phenotypic
      differentiation of strain D9(T) from B. aquatica DSM 5075(T) as well as from
      members of the genus Yersinia. From these results, it is concluded that strain
      D9(T) represents a novel species, for which the name Budvicia diplopodorum sp.
      nov. is proposed (type strain D9(T) =DSM 21983(T) = CCM 7845(T)). The description
      of the genus Budvicia is emended.

PMID- 22407791
TI  - Transfer of Pseudomonas flectens Johnson 1956 to Phaseolibacter gen. nov., in the
      family Enterobacteriaceae, as Phaseolibacter flectens gen. nov., comb. nov.
AB  - Pseudomonas flectens Johnson 1956, a plant-pathogenic bacterium on the pods of
      the French bean, is no longer considered to be a member of the genus Pseudomonas
      sensu stricto. A polyphasic approach that included examination of phenotypic
      properties and phylogenetic analyses based on 16S rRNA, rpoB and atpD gene
      sequences supported the transfer of Pseudomonas flectens Johnson 1956 to a new
      genus in the family Enterobacteriaceae as Phaseolibacter flectens gen. nov.,
      comb. nov. Two strains of Phaseolibacter flectens were studied (ATCC 12775(T) and
      LMG 2186); the strains shared 99.8 % sequence similarity in their 16S rRNA genes
      and the housekeeping gene sequences were identical. Strains of Phaseolibacter
      flectens shared 96.6 % or less 16S rRNA gene sequence similarity with members of
      different genera in the family Enterobacteriaceae and only 84.7 % sequence
      similarity with Pseudomonas aeruginosa LMG 1242(T), demonstrating that they are
      not related to the genus Pseudomonas. As Phaseolibacter flectens formed an
      independent phyletic lineage in all of the phylogenetic analyses, it could not be
      affiliated to any of the recognized genera within the family Enterobacteriaceae
      and therefore was assigned to a new genus. Cells were Gram-negative, straight
      rods, motile by means of one or two polar flagella, fermentative, facultative
      anaerobes, oxidase-negative and catalase-positive. Growth occurred in the
      presence of 0-60 % sucrose. The DNA G+C content of the type strain was 44.3 mol%.
      On the basis of phenotypic properties and phylogenetic distinctiveness,
      Pseudomonas flectens Johnson 1956 is transferred to the novel genus
      Phaseolibacter gen. nov. as Phaseolibacter flectens gen. nov., comb. nov. The
      type strain of Phaseolibacter flectens is ATCC 12775(T) = CFBP 3281(T) = ICMP
      745(T) = LMG 2187(T) = NCPPB 539(T).

PMID- 22407793
TI  - N-Terminal acetylation is critical for forming alpha-helical oligomer of alpha
      synuclein.
AB  - The aggregation of the protein alpha-synuclein (AS) is critical to the
      pathogenesis of Parkinson's disease. Although generally described as an
      unstructured monomer, recent evidence suggests that the native form of AS may be
      an alpha-helical tetramer which resists aggregation. Here, we show that N
      terminal acetylation in combination with a mild purification protocol results in
      an oligomeric form of AS with partial alpha-helical structure. N-terminal
      acetylation of AS could have important implications for both the native and
      pathological structures and functions of AS. Through our demonstration of a
      recombinant expression system, our results represent an important step toward
      biochemical and biophysical characterization of this potentially important form
      of AS.

PMID- 22407794
TI  - Metabolite profiling of CHO cells with different growth characteristics.
AB  - Mammalian cell cultures are the predominant system for the production of
      recombinant proteins requiring post-translational modifications. As protein
      yields are a function of growth performance (among others), and performance
      varies greatly between culture medium (e.g., different growth rates and peak cell
      densities), an understanding of the biological mechanisms underpinning this
      variability would facilitate rational medium and process optimization, increasing
      product yields, and reducing costs. We employed a metabolomics approach to
      analyze differences in metabolite concentrations of CHO cells cultivated in three
      different media exhibiting different growth rates and maximum viable cell
      densities. Analysis of intra- and extracellular metabolite concentrations over
      the course of the cultures using a combination of HPLC and GC-MS, readily
      detected medium specific and time dependent changes. Using multivariate data
      analysis, we identified a range of metabolites correlating with growth rate,
      illustrating how metabolomics can be used to relate gross phenotypic changes to
      the fine details of cellular metabolism.

PMID- 22407795
TI  - De novo 6.9 Mb interstitial deletion on chromosome 4q31.1-q32.1 in a girl with
      severe speech delay and dysmorphic features.
AB  - Deletion of the terminal part of long arm of chromosome 4 is a condition
      characterized by facial dysmorphisms, cardiac and limb defects, and developmental
      delay. Deletions usually involve the terminal part of the chromosome and most
      frequently are interstitial. Here, we report a de novo interstitial deletion
      resulting in a microdeletion of 6.9 Mb involving 4q31.3-q32.1 segment, detected
      by SNPs-Array technique in a 4-year-old female showing severe speech delay, mild
      facial dysmorphisms, and joint laxity. Phenotype-genotype relationships looking
      at the genes involved in this part of the chromosome were also carried out and
      data compared with those previously described.

PMID- 22407796
TI  - Biosafety evaluation of recombinant protein production in goat mammary gland
      using adenoviral vectors: preliminary study.
AB  - The production of recombinant proteins in the milk of non-transgenic goats can be
      achieved by transducing the mammary gland with recombinant adenoviral vectors.
      However, this process involves several regulatory issues. The current study
      evaluates the biosafety of this production system. We present a preliminary
      biosafety profile based on detection of adenoviral particles in different body
      fluids and the antibody response after adenoviral transduction of the goat
      mammary gland. In addition, two methods of adenoviral inactivation in milk were
      tested. Although adenoviral particles were detected in the milk until day 4 after
      transduction, they were absent in serum, saliva, urine and feces. Anti-adenovirus
      antibodies were detected in serum and milk. The virus inactivation methods
      neutralized adenoviral particles and preserved the immunological identity of the
      recombinant protein. These results support the idea of a safe production of
      recombinant proteins using adenoviral vectors.

PMID- 22407797
TI  - Screening Indian plant species for antiplasmodial properties-
      ethnopharmacological compared with random selection.
AB  - In the search for biologically active plant species, many studies have shown that
      an ethnopharmacological approach is more effective than a random collection. In
      order to determine whether this is true in the case of plant species used for the
      treatment of malaria in Orissa, India, the antiplasmodial activities of extracts
      prepared from 25 traditionally used species were compared with those of 25
      species collected randomly. As expected, plant species used traditionally for the
      treatment of malaria were more likely to exhibit antiplasmodial activity (21
      species (84%) active against Plasmodium falciparum strain 3D7) than plant species
      collected randomly (9 species (32%)). However, of the nine active randomly
      collected species, eight had not previously been reported to possess
      antiplasmodial activity while one inactive species had been reported to be active
      in another study. Of the 21 active species of traditional antimalarial
      treatments, only six had been reported previously. This study suggests that while
      the selection of traditional medicinal plants is more predictive of
      antiplasmodial study, random collections may still be of value for the
      identification of new antiplasmodial species.

PMID- 22407799
TI  - Rotenone formulation fate in Lake Davis following the 2007 treatment.
AB  - In September 2007, Lake Davis (near Portola, California) was treated by the
      California Department of Fish and Game with CFT Legumine, a rotenone formulation,
      to eradicate the invasive northern pike (Esox lucius). The objective of this
      report is to describe the fate of the five major formulation constituents
      rotenone, rotenolone, methyl pyrrolidone (MP), diethylene glycol monethyl ether
      (DEGEE), and Fennedefo 99-in water, sediment, and brown bullhead catfish
      (Ameiurus nebulosus; a rotenone-resistant species) by determination of their half
      lives (t(1/2)) and pseudo first-order dissipation rate constants (k). The
      respective t(1/2) values in water for rotenone, rotenolone, MP, DEGEE, and
      Fennedefo 99 were 5.6, 11.1, 4.6, 7.7, and 13.5 d; in sediments they were 31.1,
      31.8, 10.0, not able to calculate, and 48.5 d; and in tissues were 6.1, 12.7,
      3.7, 3.2, and 10.4 d, respectively. Components possessing low water solubility
      values (rotenone and rotenolone) persisted longer in sediments (not detectable
      after 157 d) and tissues (<212 d) compared with water, whereas the water-miscible
      components (MP and DEGEE) dissipated more quickly from all matrices, except for
      Fennedefo 99, which was the most persistent in water (83 d). None of the
      constituents was found to bioaccumulate in tissues as a result of treatment. In
      essence, the physicochemical properties of the chemical constituents effectively
      dictated their fate in the lake following treatment.

PMID- 22407800
TI  - DNA architectonics: towards the next generation of bio-inspired materials.
AB  - The use of DNA in nanobiotechnology has advanced to a stage at which almost any
      two or three dimensional architecture can be designed with high precision. The
      choice of the DNA sequences is essential for successful self-assembly, and opens
      new ways of making nanosized monomolecular assemblies with predictable structure
      and size. The inclusion of designer nucleoside analogues further adds
      functionality with addressable groups, which have an influence on the function of
      the DNA nano-objects. This article highlights the recent achievements in this
      emerging field and gives an outlook on future perspectives and applications.

PMID- 22407798
TI  - Adipose tissue and inflammatory bowel disease pathogenesis.
AB  - Creeping fat has long been recognized as an indicator of Crohn's disease (CD)
      activity. Although most patients with CD have normal or low body mass index
      (BMI), the ratio of intraabdominal fat to total abdominal fat is far greater than
      that of controls. The obesity epidemic has instructed us on the inflammatory
      nature of hypertrophic adipose tissue and similarities between mesenteric depots
      in obese and CD patients can be drawn. However, several important physiological
      differences exist between these two depots as well. While the molecular basis of
      the crosstalk between mesenteric adipose and the inflamed intestine in CD is
      largely unknown, novel evidence implicates neuropeptides along with adipocyte
      derived paracrine mediators (adipokines) as potential targets for future
      investigations and highlight adipose tissue physiology as a potential important
      determinant in the course of IBD.

PMID- 22407801
TI  - Nonclinical vaccine safety evaluation: advantages of continuous temperature
      monitoring using abdominally implanted data loggers.
AB  - Fever has been reported as the most common adverse event after vaccination in
      infants and children. For this reason it is important that, prior to clinical
      testing of a new vaccine, change in body temperature following vaccination is
      tested carefully in nonclinical animal studies. Since both the timing and the
      height of the temperature peak after vaccination may differ from vaccine to
      vaccine, it is important that the time point for body temperature measurement
      should be chosen on a case-by-case basis with sufficient knowledge of the
      specific vaccine. In order to determine the best time point for rectal body
      temperature measurement after vaccination with a new vaccine candidate against N.
      meningitidis serogroup B, to be applied in a formal Good Laboratory Practice
      (GLP) toxicology study, miniature temperature data loggers were implanted into
      the peritoneal cavity of rabbits. The continuous body temperature monitoring
      appeared to give a complete picture of the entire body temperature kinetics after
      vaccination. The body temperature peaked at 4 h after vaccination, and this time
      point was subsequently applied in the toxicology study. Measured body temperature
      values at the selected time point of 4 h after vaccination were comparable in the
      continuous temperature setting and in the formal toxicology study, i.e. rectal
      temperature measurement at one time point. In the present study implanted
      temperature loggers were successfully used to define an adequate time point to be
      applied in determining rectal body temperature in a formal GLP toxicology study
      with a new vaccine candidate.

PMID- 22407802
TI  - Stem cell identification--in vivo lineage analysis versus in vitro isolation and
      clonal expansion.
AB  - Recently, a dispute has arisen concerning the operational definition and
      identification of epithelial stem cells. There is a current view which considers
      that epithelial stem cell identification depends solely on the in vitro isolation
      and expansion of cells from the putative stem cell. This article argues strongly
      that this is a perverse and erroneous view, and that lineage labelling, using
      genetic markers, remains the gold standard for identifying epithelial stem cells
      and for analysing their behaviour: in vitro methods show, at best, clonogenic
      potential but not fate, and constitute ancillary support for conclusions drawn
      from lineage analysis.

PMID- 22407803
TI  - Polar constituents of Marrubium thessalum Boiss. & Heldr. (Lamiaceae) and their
      cytotoxic/cytostatic activity.
AB  - The methanol extract of the aerial parts of Marrubium thessalum Boiss. & Heldr.
      (Lamiaceae) afforded 30 phenolic metabolites, belonging to the classes of
      phenylethanoid glycosides, flavonoids and simple phenolic compounds. The crude
      methanol extract as well as the secondary metabolites were screened for their
      cytotoxic/cytostatic effects against four human cancer cell lines, specifically
      HeLa, MCF-7, FM3 and HCT-116 and demonstrated considerable cell growth-inhibitory
      activity. The differential cytotoxicity of the compounds implied possible
      structure-activity relationships. Selected compounds were evaluated for their
      toxicity against human peripheral blood mononuclear cells, where some of them
      showed marginal toxic effects. The results suggest that M. thessalum produces
      secondary metabolites that demonstrate selective anticancer activity
      concomitantly with reduced toxicity on lymphocytes. The structure of such
      compounds can eventually lead to the development of novel pharmaceutical agents.

PMID- 22407805
TI  - Structural and pharmacological characterization of phenylalanine-based AMPA
      receptor antagonists at kainate receptors.
AB  - Continued efforts into the discovery of ligands that target ionotropic glutamate
      receptors (iGluRs) are important for studies of the physiological roles of the
      various iGluR subtypes as well as for the search for drugs that can be used in
      the treatment of diseases of the central nervous system. A new series of
      phenylalanine derivatives that target iGluRs was reported to bind AMPA receptors.
      Herein we report our studies of these compounds at the kainate receptors GluK1-3.
      Several compounds bind with micromolar affinity at GluK1 and GluK3, but do not
      bind GluK2. The crystal structure of the most potent compound in the ligand
      binding domain of GluK1 revealed different modes of binding to GluK1 and GluA2,
      due primarily to residues Ser741 (GluK1) and Met729 (GluA2). The compound was
      shown to be slightly more potent at GluK1 than at AMPA receptors and to induce a
      domain closure similar to that observed in GluK1 structures with partial
      agonists.

PMID- 22407806
TI  - The gut microbiota regulates bone mass in mice.
AB  - The gut microbiota modulates host metabolism and development of immune status.
      Here we show that the gut microbiota is also a major regulator of bone mass in
      mice. Germ-free (GF) mice exhibit increased bone mass associated with reduced
      number of osteoclasts per bone surface compared with conventionally raised (CONV
      R) mice. Colonization of GF mice with a normal gut microbiota normalizes bone
      mass. Furthermore, GF mice have decreased frequency of CD4(+) T cells and
      CD11b(+) /GR 1 osteoclast precursor cells in bone marrow, which could be
      normalized by colonization. GF mice exhibited reduced expression of inflammatory
      cytokines in bone and bone marrow compared with CONV-R mice. In summary, the gut
      microbiota regulates bone mass in mice, and we provide evidence for a mechanism
      involving altered immune status in bone and thereby affected osteoclast-mediated
      bone resorption. Further studies are required to evaluate the gut microbiota as a
      novel therapeutic target for osteoporosis.

PMID- 22407807
TI  - Rapid enantiomeric separation and simultaneous determination of phenethylamines
      by ultra high performance liquid chromatography with fluorescence and mass
      spectrometric detection: application to the analysis of illicit drugs distributed
      in the Japanese market and biological samples.
AB  - A rapid enantiomeric separation and simultaneous determination method based on
      ultra high performance liquid chromatography (UHPLC) was developed for
      phenethylamine-type abused drugs using (R)-(-)-4-(N,N-dimethylaminosulfonyl)-7-(3
      isothiocyanatopyrrolidin-1-yl)-2,1,3-benzoxadiazole ((R)-(-)-DBD-Py-NCS) as the
      chiral fluorescent derivatization reagent. The derivatives were rapidly
      enantiomerically separated by reversed-phase UHPLC using a column of 2.3-um
      octadecylsilica (ODS) particles by isocratic elution with water-methanol or water
      acetonitrile systems as the mobile phase. The proposed method was applied to the
      analysis of products containing illicit drugs distributed in the Japanese market.
      Among the products, 1-(3,4-methylenedioxyphenyl)butan-2-amine (BDB) and 1-(2
      methoxy4,5-methylenedioxyphenyl)propan-2-amine (MMDA-2) were detected in racemic
      form. Furthermore, the method was successfully applied to the analysis of hair
      specimens from rats that were continuously dosed with diphenyl(pyrrolidin-2
      yl)methanol (D2PM). Using UHPLC-fluorescence (FL) detection, (R)- and (S)-D2PM
      from hair specimens were enantiomerically separated and detected with high
      sensitivity. The detection limits of (R)- and (S)-D2PM were 0.12 and 0.21 ng/mg
      hair, respectively (signal-to-noise ratio (S/N) = 3).

PMID- 22407808
TI  - Reduced adsorption of propanil to black carbon: effect of dissolved organic
      matter loading mode and molecule size.
AB  - In the present study, the reduced adsorption of propanil on black carbon (BC)
      influenced by dissolved organic matter (DOM) was verified to be closely related
      to DOM molecule size and loading mode. Two congenetic carbons, a rice-residue
      derived BC and the reduced product (RC), were characterized by similar specific
      surface area and different surface properties. Reduced product exhibits higher
      adsorption of propanil and DOM than BC. A series of model DOMs, including tannic
      acid (TA), pentagalloylglucose (PA), 3-O-galloylmucic acid (OA), and gallic acid
      (GA), characterized by different molecule sizes and molecular weights, were used
      to evaluate the different inhibitory effects. The DOM adsorption (mmol/g) on BC
      and RC follows the order of GA > PA > OA > TA, whereas the reduction of propanil
      adsorption influenced by the model DOM follows the order of PA ~ TA > OA ~ GA.
      The suppressive degree is connected to their molecule sizes rather than to
      molecular weights. Tannic acid and PA weakened propanil adsorption more
      effectively than OA and GA because the large DOM molecules may hinder propanil
      molecules into the micropore regions. Because of the similar molecule size, TA
      and PA present a similar suppressive effect on propanil adsorption. The influence
      of the DOMs was greater when preloaded than when in competition with propanil.
      The preloading of macromolecules (TA and PA) and OA on the carbons may lead to
      secondary and primary micropore blocks, respectively. The preloading of GA may
      cause partial GA molecule sequestration in the primary micropore, thus leading to
      strong attenuation of propanil adsorption on the carbons.

PMID- 22407809
TI  - Recessive RYR1 mutations in a patient with severe congenital nemaline myopathy
      with ophthalomoplegia identified through massively parallel sequencing.
AB  - Nemaline myopathy (NM) is a group of congenital myopathies, characterized by the
      presence of distinct rod-like inclusions "nemaline bodies" in the sarcoplasm of
      skeletal muscle fibers. To date, ACTA1, NEB, TPM3, TPM2, TNNT1, and CFL2 have
      been found to cause NM. We have identified recessive RYR1 mutations in a patient
      with severe congenital NM, through high-throughput screening of congenital
      myopathy/muscular dystrophy-related genes using massively parallel sequencing
      with target gene capture. The patient manifested fetal akinesia, neonatal severe
      hypotonia with muscle weakness, respiratory insufficiency, swallowing
      disturbance, and ophthalomoplegia. Skeletal muscle histology demonstrated
      nemaline bodies and small type 1 fibers, but without central cores or minicores.
      Congenital myopathies, a molecularly, histopathologically, and clinically
      heterogeneous group of disorders are considered to be a good candidate for
      massively parallel sequencing.

PMID- 22407811
TI  - Population-based study of the need for cholecystectomy after obesity surgery.
AB  - BACKGROUND: Weight loss following obesity surgery is associated with gallstone
      formation, but there is limited evidence on whether prophylactic cholecystectomy
      is indicated during obesity surgery. The aim of this study was to clarify the
      need for cholecystectomy following obesity surgery. METHODS: A Swedish
      nationwide, population-based cohort study was conducted during the 22-year
      interval 1987-2008. Need for later cholecystectomy for gallstone disease was
      assessed in patients who had undergone obesity surgery in comparison with the
      general population of corresponding age, sex and calendar year. This need was
      also compared with the need for cholecystectomy in cohorts of patients who had
      undergone antireflux surgery and appendicectomy. Standardized incidence ratios
      (SIRs) with 95 per cent confidence intervals (c.i.) were calculated to estimate
      the relative risk. RESULTS: In the obesity surgery cohort of 13 443 patients, the
      observed number of cholecystectomies (1149, 8.5 per cent) exceeded the expected
      number by over fivefold (SIR 5.5, 95 per cent c.i. 5.1 to 5.8). The observed need
      for imperative cholecystectomy (for cholecystitis, cholangitis, pancreatitis, or
      jaundice; 427, 3.2 per cent) was also greater than expected (SIR 5.2, 4.7 to
      5.7). The SIR peaked 7-24 months after obesity surgery and decreased with longer
      follow-up. The SIRs for cholecystectomy after antireflux surgery and
      appendicectomy were 2.4 (2.2 to 2.6) and 1.7 (1.6 to 1.7) respectively.
      CONCLUSION: An increased need for cholecystectomy after obesity surgery was
      confirmed, but was probably partly due to an increased detection of gallbladder
      disease only because of the surgery; the individual's risk of imperative
      cholecystectomy was low. Therefore, prophylactic cholecystectomy might not be
      recommended during obesity surgery.

PMID- 22407812
TI  - Betulinic acid decreases ER-negative breast cancer cell growth in vitro and in
      vivo: role of Sp transcription factors and microRNA-27a:ZBTB10.
AB  - Betulinic acid (BA), a pentacyclic triterpenoid isolated from tree bark is
      cytotoxic to cancer cells. There is evidence that specificity proteins (Sps),
      such as Sp1, Sp3, and Sp4, are overexpressed in tumors and contribute to the
      proliferative and angiogenic phenotype associated with cancer cells. The
      objective of this study was to determine the efficacy of BA in decreasing the Sps
      expression and underlying mechanisms. Results show that BA decreased
      proliferation and induced apoptosis of estrogen-receptor-negative breast cancer
      MDA-MB-231 cells. The BA-induced Sp1, Sp3, and Sp4 downregulation was accompanied
      by increased zinc finger ZBTB10 expression, a putative Sp-repressor and decreased
      microRNA-27a levels, a microRNA involved in the regulation of ZBTB10. Similar
      results were observed in MDA-MB-231 cells transfected with ZBTB10 expression
      plasmid. BA induced cell cycle arrest in the G2/M phase and increased Myt-1 mRNA
      (a microRNA-27a target gene), which causes inhibition in G2/M by phosphorylation
      of cdc2. The effects of BA were reversed by transient transfection with a mimic
      of microRNA-27a. In nude mice with xenografted MDA-MB-231 cells, tumor size and
      weight were significantly decreased by BA treatment. In tumor tissue, ZBTB10 mRNA
      was increased while mRNA and protein of Sp1, Sp3 and Sp4, as well as mRNA of
      vascular endothelial growth factor receptor (VEGFR), survivin and microRNA-27a
      were decreased by BA. In lungs of xenografted mice, human beta2-microglobulin
      mRNA was decreased in BA-treated animals. These results show that the anticancer
      effects of BA are at least in part based on interactions with the microRNA-27a
      ZBTB10-Sp-axis causing increased cell death.

PMID- 22407813
TI  - Carbon-dot-based dual-emission nanohybrid produces a ratiometric fluorescent
      sensor for in vivo imaging of cellular copper ions.
AB  - A sensitive biosensor: A strategy for the intracellular imaging of Cu(2+)  ions
      has been developed by integrating a recognition molecule, N-(2-aminoethyl)
      N,N,N'tris(pyridin-2-ylmethyl)ethane-1,2-diamine (AE-TPEA), into a hybrid system
      composed of carbon and CdSe/ZnS quantum dots.

PMID- 22407815
TI  - One-pot hydrothermal synthesis of heterostructured ZnO/ZnS nanorod arrays with
      high ethanol-sensing properties.
AB  - ZnO/ZnS heterostructured nanorod arrays with uniform diameter and length were
      synthesized from zinc substrates in a one-pot procedure by using a simple
      hydrothermal method. Structural characterization by HRTEM indicated that the
      heterostructured nanorods were composed of parallel segments of wurtzite-type ZnO
      and zinc-blende ZnS, with a distinct interface along the axial direction, which
      revealed the epitaxial relationship, ZnO (1010) and ZnS (111). The as-prepared
      ZnO/ZnS nanorods showed only two green emissions at around 523 nm and 576 nm. We
      also found that the nanorods exhibited high sensitivity to ethanol at relatively
      low temperatures, owing to their smaller size and structure.

PMID- 22407814
TI  - Structural and enzymatic characterization of BacD, an L-amino acid dipeptide
      ligase from Bacillus subtilis.
AB  - BacD is an ATP-dependent dipeptide ligase responsible for the biosynthesis of L
      alanyl-L-anticapsin, a precursor of an antibiotic produced by Bacillus spp. In
      contrast to the well-studied and phylogenetically related D-alanine: D-alanine
      ligase (Ddl), BacD synthesizes dipeptides using L-amino acids as substrates and
      has a low substrate specificity in vitro. The enzyme is of great interest because
      of its potential application in industrial protein engineering for the
      environmentally friendly biological production of useful peptide compounds, such
      as physiologically active peptides, artificial sweeteners and antibiotics, but
      the determinants of its substrate specificity and its catalytic mechanism have
      not yet been established due to a lack of structural information. In this study,
      we report the crystal structure of BacD in complex with ADP and an intermediate
      analog, phosphorylated phosphinate L-alanyl-L-phenylalanine, refined to 2.5-A
      resolution. The complex structure reveals that ADP and two magnesium ions bind in
      a manner similar to that of Ddl. However, the dipeptide orientation is reversed,
      and, concomitantly, the entrance to the amino acid binding cavity differs in
      position. Enzymatic characterization of two mutants, Y265F and S185A,
      demonstrates that these conserved residues are not catalytic residues at least in
      the reaction where L-phenylalanine is used as a substrate. On the basis of the
      biochemical and the structural data, we propose a reaction scheme and a catalytic
      mechanism for BacD.

PMID- 22407816
TI  - Evaluation of glutathione s-transferase as toxicity indicator for roxarsone and
      arsanilic acid in Eisenia fetida.
AB  - Different compounds can induce stress response by targeting specific genes.
      Studies related to elucidating the detoxification and adaptive responses of
      proteins like glutathione-s-transferase (GST) can be helpful in better
      understanding toxicity. Roxarsone and arsanilic acid, which have been
      exhaustively used as animal and poultry feed additives, pose a threat to the
      environment and human health. GST enzyme bioassay revealed fluctuations in
      response to different concentrations of roxarsone and arsanilic acid at different
      time intervals. The highest GST enzyme activity (40.51%) was observed on day 15
      of treatment with roxarsone. On the other hand, arsanilic acid caused the maximum
      enzyme activity (52.11%) on day 10 of treatment. During this study, the full
      length gene sequence of GST, having the size 984 bp (Genbankno. HQ693699), was
      achieved from Eisenia fetida and established as a biomarker to assess the
      toxicity of roxarsone and arsanilic acid. The deduced protein has a computed
      molecular mass of 23.56 kDa and a predicted isoelectric point of 9.92.
      Quantitative real-time PCR revealed significant differential gene expression in
      response to roxarsone and arsanilic acid treatment as compared with control
      treatment. Roxarsone caused the highest gene expression of 7.0-fold increase over
      control on day 15 of treatment, whereas arsanilic acid resulted in the highest
      gene expression reaching to 14.56-fold as compared with control. This study is
      helpful in understanding the role of GST as a potential biomarker for chemicals
      like roxarsone and arsanilic acid, which can pollute the food chain.

PMID- 22407817
TI  - A new isoflavone glycitein 7-O-beta-D-glucoside 4''-O-methylate, isolated from
      Cordyceps militaris grown on germinated soybeans extract, inhibits EGF-induced
      mucus hypersecretion in the human lung mucoepidermoid cells.
AB  - A new isoflavone glycitein 7-O-beta-d-glucoside 4''-O-methylate (CGLM) has been
      isolated recently from Cordyceps militaris grown on germinated soybean extract
      and has antioxidant activity. In the present study, CGLM was investigated for its
      suppression of airway mucous hyper-secretion in epidermal growth factor (EGF)
      treated human lung mucoepidermoid cells. NCI-H292 cells were treated with CGLM
      for 1 h, followed by EGF treatment for 24 h. The decrease in cyclooxygenase-2
      (COX-2) production was correlated with reduced levels of protein and mRNA of
      inducible matrix metalloproteinase 9 (MMP-9) and also MUC5AC gene expression.
      CGLM directly inhibited down-regulated NF-kappaB activity, and significantly
      inhibited the phosphorylation of p38 and ERK1/2 (p42/p44) in NCI-H292 cells.
      These results suggest that CGLM protects NCI-H292 cells from EGF-induced damage
      by down-regulation of COX-2, MMP-9 and MUC5AC gene expression, mediated via
      blocking the NF-kappa-B and p38/ERK MAPK pathways.

PMID- 22407818
TI  - Aromatase inhibitor treatment of breast cancer cells increases the expression of
      let-7f, a microRNA targeting CYP19A1.
AB  - Aromatase inhibitors (AIs) are considered the gold standard of endocrine therapy
      for oestrogen receptor-positive postmenopausal breast cancer patients. AI
      treatment was reported to result in marked alterations of genetic profiles in
      cancer tissues but its detailed molecular mechanisms have not been elucidated.
      Therefore, we profiled miRNA expression before and after treatment with letrozole
      in MCF-7 co-cultured with primary breast cancer stromal cells. Letrozole
      significantly altered the expression profiles of cancer miRNAs in vitro. Among
      the elevated miRNAs following letrozole treatment, computational analysis
      identified let-7f, a tumour-suppressor miRNA which targeted the aromatase gene
      (CYP19A1) expression. Quantitative real-time PCR assay using MCF-7 and SK-BR-3
      cells as well as clinical specimens of a neoadjuvant study demonstrated a
      significant inverse correlation between aromatase mRNA and let-7f expression. In
      addition, high let-7f expression was significantly correlated with low aromatase
      protein levels evaluated by both immunohistochemistry and the western blotting
      method in breast cancer cases. Results of 3'UTR luciferase assay also
      demonstrated the actual let-7f binding sites in CYP19A1, indicating that let-7f
      directly targets the aromatase gene. Subsequent WST-8 and migration assays
      performed in let-7f-transfected MCF-7 and SK-BR-3 cells revealed a significant
      decrement of their proliferation and migration. These findings all demonstrated
      that let-7f, a tumour suppressor miRNA in breast cancer, directly targeted the
      aromatase gene and was restored by AI treatment. Therefore, AIs may exert tumour
      suppressing effects upon breast cancer cells by suppressing aromatase gene
      expression via restoration of let-7f.

PMID- 22407819
TI  - Detection methods for autologous blood doping.
AB  - The use of blood doping is forbidden by the World Anti-Doping Agency. Several
      practices, such as blood transfusions are used to increase oxygen delivery to
      muscles and all of them are highly pursued. In this regard, the development of
      accurate methodologies for detecting these prohibited practices is one of the
      current aims of the anti-doping control laboratories. Flow cytometry methods are
      able to detect allogeneic blood transfusions but there is no official methodology
      available to detect autologous blood transfusions. This paper reviews protocols,
      including the Athlete Biological Passport, that use indirect markers to detect
      misuse of blood transfusions, especially autologous blood transfusions. The
      methods of total haemoglobin mass measurements and the detection of metabolites
      of blood bags plasticizers in urine are reviewed. The latter seems to be an
      important step forward because it is a fast screening method and it is based on
      urine, a fluid widely available for doping control. Other innovative approaches
      to blood transfusion detection are also mentioned. A combination of the reported
      methodologies and the implementation of the Athlete Biological Passport is
      becoming a promising approach.

PMID- 22407820
TI  - Adalimumab therapy in Crohn's disease of the ileal pouch.
AB  - BACKGROUND: Crohn's disease (CD) of the pouch can develop in patients with ileal
      pouch-anal anastomosis, resulting in significant morbidities, even pouch failure.
      The aim of this study was to evaluate short- and long-term outcome of adalimumab
      (ADA) in treating these patients. METHODS: A total of 48 patients who received
      ADA for CD of the pouch from June 2006 to June 2011 were identified from our
      prospectively maintained Pouchitis Registry Complete clinical response was
      defined as the resolution of symptoms as well as the modified Pouchitis Disease
      Activity Index (mPDAI) score being less than 5. Partial clinical response was
      defined as improvement in symptoms as well as a reduction in mPDAI score of 2 or
      more. Endoscopic mucosal healing status before and after therapy was recorded.
      RESULTS: At a short follow-up of median 8 weeks, 24 (50%) patients had complete
      response, 10 (21%) had partial response, and 14 (29%) had no response. After a
      median follow-up of 25.1 months, 16 (33%) patients had a complete response, 10
      (21%) had a partial response, and 22 (46%) had no response. At the end of the
      follow-up, 13 (27%) patients achieved mucosal healing. A total of nine (19%)
      patients eventually developed pouch failure. Patients with a long-term response
      had a significantly higher mucosal healing rate (60.9% vs. 28.6%, P = 0.032) and
      significantly lower median mPDAI score (2.0 vs. 5.0, P = 0.004) at the first
      follow-up evaluation than those with no long-term response. Multivariate analysis
      showed concurrent endoscopic stricture dilation (hazard ratio = 5.9; 95%
      confidence interval: 1.6, 21.2) increased the chance for the long-term response
      to ADA. One patient developed multiple sclerosis during the therapy. CONCLUSIONS:
      ADA treatment, particularly in conjunction with endoscopic therapy, may help
      rescue a subgroup of patients with CD of the pouch from having surgery.

PMID- 22407821
TI  - Reactivity of bispropargyl sulfones under basic conditions: interplay between
      Garratt-Braverman and Schmittel/Myers-Saito cyclization pathway.
AB  - The preference for Garratt-Braverman (GB) over Myers-Saito (MS) and Schmittel
      (SCM) cyclizations has recently been demonstrated in sulfones capable of
      undergoing all three of the processes. As the GB cyclization is a self-quenching
      process, there is a need to change the selectivity to the non-self-quenching MS
      or SCM pathway so as to enhance the DNA-cleaving efficiency that operates through
      the radical-mediated process. Herein we report a conformational constraint-based
      strategy developed by using computations (M06-2X/6-31+G*) to switch the
      selectivity from GB to MS/SCM pathway which also results in greater DNA-cleavage
      activity. The preference for GB could be brought back by easing the constraint
      with the help of spacers.

PMID- 22407822
TI  - Modular multiple sensors information management for computer-integrated surgery.
AB  - BACKGROUND: In the past 20 years, technological advancements have modified the
      concept of modern operating rooms (ORs) with the introduction of computer
      integrated surgery (CIS) systems, which promise to enhance the outcomes, safety
      and standardization of surgical procedures. With CIS, different types of sensor
      (mainly position-sensing devices, force sensors and intra-operative imaging
      devices) are widely used. Recently, the need for a combined use of different
      sensors raised issues related to synchronization and spatial consistency of data
      from different sources of information. METHODS: In this study, we propose a
      centralized, multi-sensor management software architecture for a distributed CIS
      system, which addresses sensor information consistency in both space and time.
      The software was developed as a data server module in a client-server
      architecture, using two open-source software libraries: Image-Guided Surgery
      Toolkit (IGSTK) and OpenCV. The ROBOCAST project (FP7 ICT 215190), which aims at
      integrating robotic and navigation devices and technologies in order to improve
      the outcome of the surgical intervention, was used as the benchmark. An
      experimental protocol was designed in order to prove the feasibility of a
      centralized module for data acquisition and to test the application latency when
      dealing with optical and electromagnetic tracking systems and ultrasound (US)
      imaging devices. RESULTS: Our results show that a centralized approach is
      suitable for minimizing synchronization errors; latency in the client-server
      communication was estimated to be 2 ms (median value) for tracking systems and 40
      ms (median value) for US images. CONCLUSION: The proposed centralized approach
      proved to be adequate for neurosurgery requirements. Latency introduced by the
      proposed architecture does not affect tracking system performance in terms of
      frame rate and limits US images frame rate at 25 fps, which is acceptable for
      providing visual feedback to the surgeon in the OR.

PMID- 22407823
TI  - Porous scaffold architecture guides tissue formation.
AB  - Critical-sized bone defect regeneration is a remaining clinical concern. Numerous
      scaffold-based strategies are currently being investigated to enable in vivo bone
      defect healing. However, a deeper understanding of how a scaffold influences the
      tissue formation process and how this compares to endogenous bone formation or to
      regular fracture healing is missing. It is hypothesized that the porous scaffold
      architecture can serve as a guiding substrate to enable the formation of a
      structured fibrous network as a prerequirement for later bone formation. An
      ovine, tibial, 30-mm critical-sized defect is used as a model system to better
      understand the effect of the scaffold architecture on cell organization, fibrous
      tissue, and mineralized tissue formation mechanisms in vivo. Tissue regeneration
      patterns within two geometrically distinct macroscopic regions of a specific
      scaffold design, the scaffold wall and the endosteal cavity, are compared with
      tissue formation in an empty defect (negative control) and with cortical bone
      (positive control). Histology, backscattered electron imaging, scanning small
      angle X-ray scattering, and nanoindentation are used to assess the morphology of
      fibrous and mineralized tissue, to measure the average mineral particle thickness
      and the degree of alignment, and to map the local elastic indentation modulus.
      The scaffold proves to function as a guiding substrate to the tissue formation
      process. It enables the arrangement of a structured fibrous tissue across the
      entire defect, which acts as a secondary supporting network for cells.
      Mineralization can then initiate along the fibrous network, resulting in bone
      ingrowth into a critical-sized defect, although not in complete bridging of the
      defect. The fibrous network morphology, which in turn is guided by the scaffold
      architecture, influences the microstructure of the newly formed bone. These
      results allow a deeper understanding of the mode of mineral tissue formation and
      the way this is influenced by the scaffold architecture. (c) 2012 American
      Society for Bone and Mineral Research.

PMID- 22407824
TI  - Malleability in the development of spatial reorientation.
AB  - After becoming disoriented, organisms must re-establish their position in space.
      The core knowledge position argues that reorientation relies only on extended 3D
      surfaces, and that this sensitivity operates automatically and is innately
      present. In contrast, the adaptive combination perspective argues that
      reorientation is experience-expectant and malleable, and depends on both extended
      3D surfaces and 2D feature cues. We test these divergent views by comparing young
      (Experiment 1) and mature (Experiment 2) C57BL/6 mice (Mus musculus) that have
      been housed in circular or rectangular environments. Malleability of feature cues
      was found for young mice. Malleability of incidental geometry coding was found
      for both age groups. The relative dependence on geometric and feature cues
      changed with age. Young mice weighted the feature cue more heavily than adult
      mice. In summary, as predicted by the adaptive combination approach, rearing
      environments influenced the relative use of feature and geometric cues in a
      reorientation task.

PMID- 22407825
TI  - Methionine synthase and thymidylate synthase gene polymorphisms and colorectal
      adenoma risk: the self defense forces study.
AB  - Folate-mediated one-carbon metabolism has been implicated in colorectal
      carcinogenesis. We investigated associations of functional genetic polymorphisms
      of methionine synthase (MTR), MTR reductase (MTRR), and thymidylate synthase (TS)
      with colorectal adenomas. The study subjects were 455 cases of colorectal
      adenomas and 1052 controls with no polyp at colonoscopy. Genotypes were
      determined for MTR A2756G, MTRR A66G and two polymorphisms in the TS gene, 28-bp
      tandem repeat polymorphism in the promoter enhancer region (TSER) and 6-bp
      deletion polymorphism at position 1494 in the 3' untranslated region (TS
      1494del6). We also examined the alcohol-genotype and gene-gene interactions on
      adenoma risk. The GG genotype of MTR A2756G was associated with an increased risk
      of colorectal adenomas; odds ratios for AG and GG versus AA genotype were 0.99
      (95% confidence interval 0.78-1.26) and 1.72 (1.04-2.82), respectively. The
      increase in the risk associated with MTR 2756GG genotype was evident in men with
      high alcohol consumption (>=30 mL/d), but not in those with low alcohol
      consumption (interaction P = 0.03). Men who were homozygous for the TSER double
      repeat allele had a slightly decreased risk of colorectal adenomas as compared
      with those homozygous for the TSER triple-repeat allele. Neither MTRR A66G nor TS
      1494del6 was associated with colorectal adenomas. There was no measurable
      interaction either between MTR A2756G and MTRR A66G or between TSER and TS
      1494del6. MTR A2756G appears to be associated with colorectal adenoma risk
      differently according to alcohol consumption. The MTR-catalyzed reaction may play
      an important role in the development of colorectal adenomas.

PMID- 22407826
TI  - Contaminant driven genetic erosion: a case study with Daphnia longispina.
AB  - Natural populations exposed to pollutants are predicted to experience a loss of
      genetic diversity, especially through genetic drift, gene flow (emigration),
      and/or selection (as sensitive genotypes may be lost). In the present study, the
      authors discuss the use of selectable markers and neutral markers to evaluate a
      contaminant-driven loss of genetic diversity and possible implications of genetic
      erosion on populations' viability. Viability could be reduced by altering life
      history parameters, especially due to fitness costs associated with the
      acquisition of resistance and/or by compromising the resilience and adaptation to
      future environmental changes. This discussion aims at an integrated and critical
      analysis of this topic; it is illustrated by several independent studies (each
      with its own specific objectives) that were carried out at the same location with
      Daphnia longispina populations. To the best of the authors' knowledge, this is
      the most extensively documented case study on genetic erosion of a natural
      zooplankton population. Directional selection has been found to be a main factor
      of microevolution; therefore, genetic erosion was detected by monitoring suitable
      phenotypic markers. Genetic drift was found to be probably irrelevant or masked
      by other factors, especially gene flow. Although the acquisition of resistance
      apparently did not entail genetically determined fitness costs under
      uncontaminated conditions, the present case study suggests the possibility of a
      further loss of genotypes due to some negative linkages between the sensitivity
      to potential ulterior toxicants.

PMID- 22407827
TI  - TIMP-1 deficiency leads to lethal partial hepatic ischemia and reperfusion
      injury.
AB  - Hepatic ischemia and reperfusion injury (IRI) remains an important challenge in
      clinical orthotopic liver transplantation (OLT). Tissue inhibitor of
      metalloproteinase-1 (TIMP-1) is the major endogenous regulator of matrix
      metalloproteinase-9 (MMP-9). In this study we investigated the functional
      significance of TIMP-1 expression in a well-established mouse model of partial
      liver IRI. Compared to wildtype mice, TIMP-1(-/-) mice showed further impaired
      liver function and histological preservation after IRI. Notably, TIMP-1
      deficiency led to lethal liver IRI, as over 60% of the TIMP-1(-/-) mice died
      postreperfusion, whereas all TIMP-1(+/+) mice recovered and survived surgery.
      Lack of TIMP-1 expression was accompanied by markedly high levels of MMP-9
      activity, which facilitates leukocyte transmigration across vascular barriers in
      hepatic IRI. Indeed, TIMP-1(-/-) livers were characterized by massive leukocyte
      infiltration and by up-regulation of proinflammatory mediators, including tumor
      necrosis factor alpha, interferon-gamma, and inducible nitric oxide synthase post
      IRI. The inability of TIMP-1(-/-) mice to express TIMP-1 increased the levels of
      active caspase-3 and depressed the expression of Bcl-2 and the phosphorylation of
      Akt, emphasizing an important role for TIMP-1 expression on hepatocyte survival.
      Using independent parameters of regeneration, 5-bromodeoxyuridine incorporation,
      proliferating cell nuclear antigen expression, and histone H3 phosphorylation, we
      provide evidence that hepatocyte progression into S phase and mitosis was
      impaired in TIMP-1-deficient livers after IRI. Inhibition of the cell cycle
      progression by TIMP-1 deficiency was linked to depressed levels of cyclins-D1 and
      -E and to a disrupted c-Met signaling pathway, as evidenced by reduced
      phosphorylated c-Met expression and elevated c-Met ectodomain shedding postliver
      IRI. CONCLUSION: These results support a critical protective function for TIMP-1
      expression on promoting survival and proliferation of liver cells and on
      regulating leukocyte recruitment and activation in liver IRI.

PMID- 22407828
TI  - Stem-like tumor-initiating cells isolated from IL13Ralpha2 expressing gliomas are
      targeted and killed by IL13-zetakine-redirected T Cells.
AB  - PURPOSE: To evaluate IL13Ralpha2 as an immunotherapeutic target for eliminating
      glioma stem-like cancer initiating cells (GSC) of high-grade gliomas, with
      particular focus on the potential of genetically engineered IL13Ralpha2-specific
      primary human CD8(+) CTLs (IL13-zetakine(+) CTL) to target this therapeutically
      resistant glioma subpopulation. EXPERIMENTAL DESIGN: A panel of low-passage GSC
      tumor sphere (TS) and serum-differentiated glioma lines were expanded from
      patient glioblastoma specimens. These glioblastoma lines were evaluated for
      expression of IL13Ralpha2 and for susceptibility to IL13-zetakine(+) CTL-mediated
      killing in vitro and in vivo. RESULTS: We observed that although glioma
      IL13Ralpha2 expression varies between patients, for IL13Ralpha2(pos) cases this
      antigen was detected on both GSCs and more differentiated tumor cell populations.
      IL13-zetakine(+) CTL were capable of efficient recognition and killing of both
      IL13Ralpha2(pos) GSCs and IL13Ralpha2(pos) differentiated cells in vitro, as well
      as eliminating glioma-initiating activity in an orthotopic mouse tumor model.
      Furthermore, intracranial administration of IL13-zetakine(+) CTL displayed robust
      antitumor activity against established IL13Ralpha2(pos) GSC TS-initiated
      orthotopic tumors in mice. CONCLUSIONS: Within IL13Ralpha2 expressing high-grade
      gliomas, this receptor is expressed by GSCs and differentiated tumor populations,
      rendering both targetable by IL13-zetakine(+) CTLs. Thus, our results support the
      potential usefullness of IL13Ralpha2-directed immunotherapeutic approaches for
      eradicating therapeutically resistant GSC populations.

PMID- 22407829
TI  - Squamous cell carcinoma of the lung: molecular subtypes and therapeutic
      opportunities.
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide. Next to
      adenocarcinoma, squamous cell carcinoma (SCC) of the lung is the most frequent
      histologic subtype in non-small cell lung cancer. Encouraging new treatments
      (i.e., bevacizumab, EGFR tyrosine kinase inhibitors, and ALK inhibitors) have
      afforded benefits to patients with adenocarcinoma, but unfortunately the same is
      not true for SCC. However, many genomic abnormalities are present in SCC, and
      there is growing evidence of their biologic significance. Thus, in the short
      term, the molecular characterization of patients with SCC in modern profiling
      platforms will probably be as important as deciphering the molecular genetics of
      adenocarcinoma. Patients with SCC of the lung harboring specific molecular
      defects that are actionable (e.g., fibroblast growth factor receptor 1
      amplification, discoidin domain receptor 2 mutation, and phosphoinositide 3
      kinase amplification) should be enrolled in prospective clinical trials targeting
      such molecular defects.

PMID- 22407830
TI  - Choosing phase II endpoints and designs: evaluating the possibilities.
AB  - Selecting the phase II design and endpoint to achieve the best possible chance of
      success for a confirmatory phase III study in a particular disease and treatment
      setting is challenging but critical. Simulating from existing clinical trial data
      sets and from mathematical models can be useful tools for evaluating statistical
      properties.

PMID- 22407831
TI  - Survivin is a viable target for the treatment of malignant peripheral nerve
      sheath tumors.
AB  - PURPOSE: To examine the role of survivin as a therapeutic target in preclinical
      models of human malignant peripheral nerve sheath tumors (MPNST) EXPERIMENTAL
      DESIGN: Survivin protein expression levels and subcellular localization were
      examined immunohistochemically in an MPNST tissue microarray. Human MPNST cells
      were studied in vitro and in vivo; real-time PCR, Western blotting, and
      immunocytochemical analyses were used to evaluate survivin expression and
      localization activation. Cell culture assays were used to evaluate the impact of
      anti-survivin-specific siRNA inhibition on cell growth and cell-cycle progression
      and survival. The effect of the small-molecule survivin inhibitor YM155 on local
      and metastatic MPNST growth was examined in vivo. RESULTS: Survivin was found to
      be highly expressed in human MPNSTs; enhanced cytoplasmic subcellular
      localization differentiated MPNSTs from their plexiform neurofibroma premalignant
      counterparts. Human MPNST cell lines exhibited survivin mRNA and protein
      overexpression; expression in both nuclear and cytoplasmic compartments was
      noted. Survivin knockdown abrogated MPNST cell growth, inducing G(2) cell-cycle
      arrest and marked apoptosis. YM155 inhibited human MPNST xenograft growth and
      metastasis in severe combined immunodeficient (SCID) mice. Antitumor effects were
      more pronounced in fast-growing xenografts. CONCLUSIONS: Our studies show an
      important role for survivin in human MPNST biology. Patients with MPNSTs should
      be considered for ongoing or future clinical trials that evaluate anti-survivin
      therapeutic strategies. Most importantly, future investigations should evaluate
      additional pathways that can be targeted in combination with survivin for maximal
      synergistic anti-MPNST effects.

PMID- 22407832
TI  - Dual mTORC1/2 and HER2 blockade results in antitumor activity in preclinical
      models of breast cancer resistant to anti-HER2 therapy.
AB  - PURPOSE: The PI3K/Akt/mTOR pathway is an attractive target in HER2-positive
      breast cancer that is refractory to anti-HER2 therapy. The hypothesis is that the
      suppression of this pathway results in sensitization to anti-HER2 agents.
      However, this combinatorial strategy has not been comprehensively tested in
      models of trastuzumab and lapatinib resistance. EXPERIMENTAL DESIGN: We analyzed
      in vitro cell viability and induction of apoptosis in five different cell lines
      resistant to trastuzumab and lapatinib. Inhibition of HER2/HER3 phosphorylation,
      PI3K/Akt/mTOR, and extracellular signal-regulated kinase (ERK) signaling pathways
      was evaluated by Western blotting. Tumor growth inhibition after treatment with
      lapatinib, INK-128, or the combination of both agents was evaluated in three
      different animal models: two cell-based xenograft models refractory to both
      trastuzumab and lapatinib and a xenograft derived from a patient who relapsed on
      trastuzumab-based therapy. RESULTS: The addition of lapatinib to INK-128
      prevented both HER2 and HER3 phosphorylation induced by INK-128, resulting in
      inhibition of both PI3K/Akt/mTOR and ERK pathways. This dual blockade produced
      synergistic induction of cell death in five different HER2-positive cell lines
      resistant to trastuzumab and lapatinib. In vivo, both cell line-based and patient
      derived xenografts showed exquisite sensitivity to the antitumor activity of the
      combination of lapatinib and INK-128, which resulted in durable tumor shrinkage
      and exhibited no signs of toxicity in these models. CONCLUSIONS: The simultaneous
      blockade of both PI3K/Akt/mTOR and ERK pathways obtained by combining lapatinib
      with INK-128 acts synergistically in inducing cell death and tumor regression in
      breast cancer models refractory to anti-HER2 therapy.

PMID- 22407833
TI  - Analysis of spontaneous tumor-specific CD4 T-cell immunity in lung cancer using
      promiscuous HLA-DR telomerase-derived epitopes: potential synergistic effect with
      chemotherapy response.
AB  - PURPOSE: To investigate the presence and impact of spontaneous telomerase
      specific CD4 T-cell responses in cancer patients. EXPERIMENTAL DESIGN: A
      multistep approach was used to design novel pan-HLA-DR-restricted peptides from
      telomerase. T-cell clones isolated from cancer patients were used to characterize
      the polarization of telomerase-specific CD4 response. The presence of spontaneous
      CD4 T-cell response against telomerase was monitored in 84 metastatic non-small
      cell lung cancer (NSCLC) patients before first-line chemotherapy (CT) using IFN
      gamma ELISPOT assay. Then we analyzed the impact of the pretherapeutic telomerase
      specific CD4 T immunity on clinical outcome in patients according to their
      respective response to CT. RESULTS: We described four novel telomerase-derived
      CD4 epitopes referred as universal cancer peptides (UCP) that effectively bind to
      most commonly found human MHC class II alleles. UCP-specific CD4 T-cell
      repertoire is present in human and UCP-specific CD4 T-cell clones generated from
      cancer patients exhibited high avidity and are Th1 polarized. Significant
      frequency (38%) of naturally occurring UCP-specific T-cell responses were
      detected before CT in advanced NSCLC but not in healthy volunteers. This response
      was shown to significantly increase overall survival (OS) of patients responding
      to CT (Median OS: 53 vs. 40 weeks, P = 0.034). CONCLUSIONS: These results show
      for the first time a potential synergistic effect of telomerase-specific CD4 T
      cell response with CT response in NSCLC and underline the potential role of tumor
      specific CD4 T-cell response on the efficiency of conventional anticancer
      therapy.

PMID- 22407834
TI  - The brain can be thought of as a tool.
AB  - In this paper I argue that the recent tendency to elevate neuropsychology to the
      status of the one true scientific core of studies of people thinking, feeling,
      acting and perceiving is not best understood as a simple mereological fallacy,
      that is the fallacy of ascribing certain properties of wholes to their parts, in
      particular mental concepts to the material brain as a part of a person. In
      defending Svend Brinkmann's way of undermining the claims of neuroscience against
      the criticism offered by Gaeto and Cornejo of the cognitive task-brain as tool
      proposal, I argue that a person's brain is part of the body of that person, but
      that the body is not a part of a person. Hence the use of person-concepts to
      describe brain activity is not a mereological fallacy. Rather human bodies are
      sites for people. Material tools can be fashioned or found at such sites. It is a
      fallacy to present neuroscience as the core of psychology but it is the error of
      deriving an 'ought' from an 'is' as identified by David Hume. Where to look for a
      positive guide to a philosophically respectable psychology, that is a study
      program that does justice to the phenomena of human thinking, feeling, acting and
      perceiving, without falling into logical and semantic traps. I show how to adapt
      Aristotle's schema for 'complete explanation' to this role.

PMID- 22407835
TI  - Tuning N-heterocyclic carbenes in T-shaped Pt(II) complexes for intermolecular C
      H bond activation of arenes.
AB  - Small change matters: T-shaped Pt(II) complexes with less flexible substituents,
      than, for example, isopropyl or tert-butyl groups, on N-heterocyclic carbene
      (NHC) ligands allow for C-H bond activation reactions of aromatic compounds (see
      scheme; BAr(f)(4)(-) =tetrakis[(3,5-trifluoromethyl)phenyl]borate; F yellow, Pt
      red). NHC substituents that are not highly branched prevent agostic interactions
      and reduce the barriers to achieve the C-H bond cleavage.

PMID- 22407836
TI  - Clinical epidemiology of skeletal dysplasias in South America.
AB  - Currently accepted birth prevalence for osteochondrodysplasias (OCD) of about
      2/10,000 is based on few studies from small series of cases. We conducted a study
      based on more than 1.5 million births. OCD cases were detected from 1,544,496
      births occurring and examined in 132 hospitals of ECLAMC (Latin American
      Collaborative Study of Congenital Malformations) between 2000 and 2007. Cases
      were detected and registered according to a pre-established protocol, and then
      ranked in four diagnostic evidence levels (DEL), according to available
      documentation. For the analysis of risk factors, a healthy control sample born in
      the same period was used. OCD was diagnosed in 492 newborns, resulting in a
      prevalence per 10,000 of 3.2 (95% CI: 2.9-3.5). Perinatal lethality (stillbirths
      plus early neonatal deaths) occurred in 50% of cases. Prenatal ultrasound
      diagnosis was made in 73% of cases (n = 359). Among 211 cases from the best
      documented group (DEL-1) and according to international classification, 33% of
      cases fit into the G-25 (osteogenesis imperfecta), 29% in Group-1 (FGFR3), and 8%
      in Group-18 (Bent bones). The prevalence of the main OCD types were: OI-0.74
      (0.61-0.89); thanatophoric dysplasia-0.47 (0.36-0.59); and achondroplasia-0.44
      (0.33-0.55). Paternal age (31.2 +/- 8.5), parity (2.6), and parental
      consanguinity rate (5.4%) were higher in cases than in controls (P < 0.001). In
      conclusion, the OCD overall prevalence of 3.2 per 10,000 found seems to be more
      realistic than previous estimates. This study also confirmed the high perinatal
      mortality, and the association with high paternal age, parity, and parental
      consanguinity rate.

PMID- 22407837
TI  - Robust design and optimization of retroaldol enzymes.
AB  - Enzyme catalysts of a retroaldol reaction have been generated by computational
      design using a motif that combines a lysine in a nonpolar environment with water
      mediated stabilization of the carbinolamine hydroxyl and beta-hydroxyl groups.
      Here, we show that the design process is robust and repeatable, with 33 new
      active designs constructed on 13 different protein scaffold backbones. The
      initial activities are not high but are increased through site-directed
      mutagenesis and laboratory evolution. Mutational data highlight areas for
      improvement in design. Different designed catalysts give different borohydride
      reduced reaction intermediates, suggesting a distribution of properties of the
      designed enzymes that may be further explored and exploited.

PMID- 22407838
TI  - Kavalactone metabolism in the isolated perfused rat liver.
AB  - Metabolic pathways for kavalactone metabolism in humans and rats have been
      identified, but more detailed description of the enzyme kinetics involved is
      lacking. The disposition profiles of three of the six major kavalactones (kavain,
      methysticin and desmethoxyyangonin) and their respective metabolites (p
      hydroxykavain, m,p-dihydroxykavain and p-hydroxy-5,6-dehydrokavain) were examined
      in the perfusate and bile of the isolated perfused rat liver. The metabolism of
      the kavalactones is first-order in nature with similar decay half-lives. p
      Hydroxykavain and m,p-dihydroxykavain were the only metabolites detected in the
      perfusate. Kavalactone biliary excretion was negligible.

PMID- 22407839
TI  - Synthesis, structural characterization, photophysics, and broadband nonlinear
      absorption of a platinum(II) complex with the 6-(7-benzothiazol-2'-yl-9,9-diethyl
      9 H-fluoren-2-yl)-2,2'-bipyridinyl ligand.
AB  - A platinum complex with the 6-(7-benzothiazol-2'-yl-9,9-diethyl-9H-fluoren-2-yl)
      2,2'-bipyridinyl ligand (1) was synthesized and the crystal structure was
      determined. UV/Vis absorption, emission, and transient difference absorption of 1
      were systematically investigated. DFT calculations were carried out on 1 to
      characterize the electronic ground state and aid in the understanding of the
      nature of low-lying excited electronic states. Complex 1 exhibits intense
      structured (1)pi-pi* absorption at lambda(abs)<440 nm, and a broad, moderate
      (1)MLCT/(1)LLCT transition at 440-520 nm in CH(2)Cl(2) solution. A structured
      (3)pi-pi*/(3)MLCT emission at about 590 nm was observed at room temperature and
      at 77 K. Complex 1 exhibits both singlet and triplet excited-state absorption
      from 450 nm to 750 nm, which are tentatively attributed to the (1)pi-pi* and
      (3)pi-pi* excited states of the 6-(7-benzothiazol-2'-yl-9,9-diethyl-9H-fluoren-2
      yl)-2,2'-bipyridine ligand, respectively. Z-scan experiments were conducted by
      using ns and ps pulses at 532 nm, and ps pulses at a variety of visible and near
      IR wavelengths. The experimental data were fitted by a five-level model by using
      the excited-state parameters obtained from the photophysical study to deduce the
      effective singlet and triplet excited-state absorption cross sections in the
      visible spectral region and the effective two-photon absorption cross sections in
      the near-IR region. Our results demonstrate that 1 possesses large ratios of
      excited-state absorption cross sections relative to that of the ground-state in
      the visible spectral region; this results in a remarkable degree of reverse
      saturable absorption from 1 in CH(2)Cl(2) solution illuminated by ns laser pulses
      at 532 nm. The two-photon absorption cross sections in the near-IR region for 1
      are among the largest values reported for platinum complexes. Therefore, 1 is an
      excellent, broadband, nonlinear absorbing material that exhibits strong reverse
      saturable absorption in the visible spectral region and large two-photon-assisted
      excited-state absorption in the near-IR region.

PMID- 22407842
TI  - High-performance inverted polymer solar cells with solution-processed titanium
      chelate as electron-collecting layer on ITO electrode.
AB  - High-performance inverted polymer solar cells (PSCs) with solution-processed
      titanium chelate TIPD as electron collecting layer are reported. The power
      conversion efficiency (PCE) of the inverted PSC with a-TIPD buffer layer with
      thermal annealing at 150  degrees C for 10 min reached 7.4% under the
      illumination of AM1.5, 100 mW/cm(2), which is increased by 16% in comparison with
      that (6.4%) of the device in the conventional structure. The PCE of 7.4% is the
      highest among the inverted PSCs reported so far in the literature.

PMID- 22407843
TI  - Furanocoumarins in celeriac from different farming systems: a 3-year study.
AB  - BACKGROUND: The aim of this 3-year study was to investigate the effect of
      different celeriac cultivation strategies on the content of naturally occurring
      toxicants furanocoumarins, represented by psoralen, bergapten, xanthotoxin and
      isopimpinellin. The products from organic farming in which anaerobically
      fermented pig slurry was used were compared against those obtained from other
      treatment systems: mineral, combined and non-fertilised. RESULTS: The average
      levels of furanocoumarins for all 3 years (determined by gas chromatography-mass
      spectrometry) in varieties Albin and Kompakt were 2.6 mg kg-1 and 10.2 mg kg-1,
      respectively. In all crop years higher levels were found in variety Kompakt. By
      using linear discriminant analysis it was possible to separate the whole data set
      according to variety from 85.7%, in individual crop years the recognition ability
      was more than 90%. According to the crop year, it was possible to separate tested
      samples from 70.8%, for individual variety the separation was 100%. CONCLUSIONS:
      The method of fertilisation did not have a significant effect on the levels of
      plant secondary metabolites, furanocoumarins. The climatic conditions, in
      particular the growing periods and the celeriac variety, had an important role in
      the occurrence of furanocoumarins.

PMID- 22407844
TI  - Tissue factor antisense deoxyoligonucleotide prevents monocrotaline/LPS
      hepatotoxicity in mice.
AB  - Tissue factor (TF) is a membranous glycoprotein that functions as a receptor for
      coagulation factor VII/VIIa and activates the coagulation system when blood
      vessels or tissues are damaged. TF was upregulated in our monocrotaline
      (MCT)/lipopolysaccharide (LPS) hepatotoxicity model. We tested the hypothesis
      that TF-dependent fibrin deposition and lipid peroxidation in the form of
      oxidized low-density-lipoprotein (ox-LDL) accumulation contribute to liver
      inflammation induced by MCT/LPS in mice. In the present study, we blocked TF
      using antisense oligodeoxynucleotides against mouse TF (TF-ASO). TF-ASO (5.6 mg
      kg(-1) ) was given i.v. to ND4 male mice 30 min after administration of MCT (200
      mg kg(-1) ) p.o. followed after 3.5 h by LPS i.p. (6 mg kg(-1) ). Blood alanine
      aminotransferase (ALT), TF, ox-LDL, platelets, hematocrit and keratinocyte
      derived chemokine (KC) levels were evaluated in different treatment groups.
      Fibrin deposition and ox-LDL accumulation were also analyzed in the liver
      sections using immunofluorescent staining. The results showed that TF-ASO
      significantly restored blood ALT, hematocrit and KC levels, distorted after
      MCT/LPS co-treatment, as well as preventing the accumulation of ox-LDL and the
      deposition of fibrin in the liver tissues, and thereby inhibited liver injury
      caused by MCT/LPS. In a separate experiment, TF-ASO administration significantly
      prolonged animal survival. The current study demonstrates that TF is associated
      with MCT/LPS-induced liver injury. Administration of TF-ASO successfully
      prevented this type of liver injury.

PMID- 22407845
TI  - Reaction of frustrated Lewis pairs with ketones and esters.
AB  - The frustrated Lewis pair (FLP) Mes(2)PCH(2)CH(2)B(C(6)F(5))(2) (1) reacts with
      an enolizable conjugated ynone by 1,4-addition involving enolate tautomerization
      to give an eight-membered zwitterionic heterocycle. The conjugated endione PhCO
      CH=CH-COPh reacts with the intermolecular FLP tBu(3)P/B(C(6)F(5))(3) by a simple
      1,4-addition to an enone subunit. The same substrate undergoes a more complex
      reaction with the FLP 1 that involves internal acetal formation to give a
      heterobicyclic zwitterionic product. FLP 1 reacts with dimethyl maleate by
      selective overall addition to the C=C double bond to give a six-membered
      heterocycle. It adds analogously to the triple bond of an acetylenic ester to
      give a similarly structured six-membered heterocycle. The intermolecular FLP P(o
      tolyl)(3)/B(C(6)F(5))(3) reacts analogously with acetylenic ester by trans
      addition to the carbon-carbon triple bond. An excess of the intermolecular FLP
      tBu(3)P/B(C(6)F(5))(3), which contains a more nucleophilic phosphane, reacts
      differently with acetylenic ester examples, namely by O-C(alkyl) bond cleavage to
      give the {R-CO(2)[B(C(6)F(5))(3)](2)(-)}[alkyl-PtBu(3)(+)] salts. Simple aryl or
      alkyl esters react analogously by using the borane-stabilized carboxylates as
      good leaving groups. All essential products were characterized by X-ray
      diffraction.

PMID- 22407847
TI  - Acetazolamide for severe apnea in Pitt-Hopkins syndrome.

PMID- 22407846
TI  - Congenic mice provide in vivo evidence for a genetic locus that modulates
      intrinsic transforming growth factor beta1-mediated signaling and bone
      acquisition.
AB  - Osteoporosis, the most common skeletal disorder, is characterized by low bone
      mineral density (BMD) and an increased risk of fragility fractures. BMD is the
      best clinical predictor of future osteoporotic fracture risk, but is a complex
      trait controlled by multiple environmental and genetic determinants with
      individually modest effects. Quantitative trait locus (QTL) mapping is a powerful
      method for identifying chromosomal regions encompassing genes involved in shaping
      complex phenotypes, such as BMD. Here we have applied QTL analysis to male and
      female genetically-heterogeneous F(2) mice derived from a cross between C57BL/6
      and DBA/2 strains, and have identified 11 loci contributing to femoral BMD.
      Further analysis of a QTL on mouse chromosome 7 following the generation of
      reciprocal congenic strains has allowed us to determine that the high BMD trait,
      which tracks with the DBA/2 chromosome and exerts equivalent effects on male and
      female mice, is manifested by enhanced osteogenic differentiation of mesenchymal
      stem cells (MSCs) in vitro and by increased growth of metatarsal bones in short
      term primary culture. An insertion/deletion DNA polymorphism in Ltbp4 exon 12
      that causes the in-frame removal of 12 codons in the DBA/2-derived gene maps
      within 0.6 Mb of the marker most tightly linked to the QTL. LTBP4, one of four
      paralogous mouse proteins that modify the bioavailability of the transforming
      growth factor beta (TGF-beta) family of growth factors, is expressed in
      differentiating MSC-derived osteoblasts and in long bones, and reduced
      responsiveness to TGF-beta1 is observed in MSCs of mice homozygous for the DBA/2
      chromosome 7. Taken together, our results identify a potential genetic and
      biochemical relationship between decreased TGF-beta1-mediated signaling and
      enhanced femoral BMD that may be regulated by a variant LTBP4 molecule.

PMID- 22407848
TI  - Prevalence of multimorbidity in medical inpatients.
AB  - OBJECTIVE: To validate the estimates of the prevalence of multimorbidity based on
      administrative hospital discharge data, with medical records and chart reviews as
      benchmarks. DESIGN: Retrospective cohort study. SETTING: Medical division of a
      tertiary care teaching hospital. PARTICIPANTS: A total of 170 medical inpatients
      admitted from the emergency unit in January 2009. MAIN MEASURES: The prevalence
      of multimorbidity for three different definitions (>=2 diagnoses, >=2 diagnoses
      from different ICD-10 chapters, and >=2 medical conditions as defined by
      Charlson/Deyo) and three different data sources (administrative data, chart
      reviews, and medical records). RESULTS: The prevalence of multimorbidity in
      medical inpatients derived from administrative data, chart reviews and medical
      records was very high and concurred for the different definitions of
      multimorbidity (>=2 diagnoses: 96.5%, 95.3%, and 92.9% [p = 0.32], >=2 diagnoses
      from different ICD-10 chapters: 86.5%, 90.0%, and 85.9% [p = 0.46], and >=2
      medical conditions as defined by Charlson/Deyo: 48.2%, 50.0%, and 46.5% [p =
      0.81]). The agreement of rating of multimorbidity for administrative data and
      chart reviews and administrative data and medical records was 94.1% and 93.0%
      (kappa statistics 0.47) for >=2 diagnoses; 86.0% and 86.5% (kappa statistics
      0.52) for >=2 diagnoses from different ICD-10 chapters; and 82.9% and 85.3%
      (kappa statistics 0.69) for >=2 medical conditions as defined by Charlson/Deyo.
      CONCLUSION: Estimates of the prevalence of multimorbidity in medical inpatients
      based on administrative data, chart reviews and medical records were very high
      and congruent for the different definitions of multimorbidity. Agreement for
      rating multimorbidity based on the different data sources was moderate to good.
      Administrative hospital discharge data are a valid source for exploring the
      burden of multimorbidity in hospital settings.

PMID- 22407849
TI  - Design of a wireless anchoring and extending micro robot system for
      gastrointestinal tract.
AB  - BACKGROUND: Diagnosis and treatment using a conventional endoscope in the
      gastrointestinal (GI) tract are very common nowadays. However, endoscopy has some
      disadvantages. METHODS: This paper describes a wireless micro-robot for active
      locomotion in the GI tract. After design and analysis of the anchoring-extending
      gait, two mechanisms were developed to meet the gait requirements. These
      actuation and transmission mechanisms were demonstrated in detail to explain the
      gait implementation. The mechanisms were driven by a micro-brush direct current
      motor with a micro-normal module (m = 0.2 mm) gearbox. The force of the
      mechanisms was tested to guarantee the sufficiency of the gait and the safety of
      the robot. After mounting a dedicated video capture unit and wireless power
      receiving coils, in vitro experiments were conducted to show the feasibility of
      locomotion by wireless power supply. RESULTS: The assembled micro-robot was 13 mm
      in diameter and 90 mm in length, with a velocity of 1 mm/s at 500 mW power
      consumption. CONCLUSIONS: The proposed anchoring and extending intestinal micro
      robot met the requirements of intestinal disease diagnosis and treatment.

PMID- 22407850
TI  - PCB concentrations in shrimp from major import markets and the United States.
AB  - Currently, environmental studies describing levels of polychlorinated biphenyls
      (PCBs) in imported shrimp are limited, particularly studies of aquaculture
      shrimp. In the present study, we measured concentrations of the 209 PCB congeners
      in 84 uncooked, warm-water shrimp samples from the United States and 14 other
      countries in three continents. Total PCB and dioxin-like PCB (DL-PCB) levels were
      not significantly different between wild-caught and farm-raised shrimp, and the
      distribution of total PCB levels did not vary considerably by country of origin
      although significant differences were observed in some cases. Regional trends in
      both total PCB and DL-PCB concentrations were observed, with the highest
      concentrations measured in shrimp from North America followed by Asia and then
      South America. The lower chlorinated homologues (i.e., mono-, di-, and tri-PCBs)
      generally comprised a greater fraction of the total levels measured in farm
      raised shrimp and shrimp from Asia and South America whereas higher chlorinated
      homologues (i.e., hepta-, octa-, nona-, and deca-PCBs) contributed more to levels
      in wild-caught shrimp and shrimp from North America. Estimated daily intake of
      PCBs associated with shrimp consumption ranged from 2 pg/kg/d (shrimp from South
      America) to 15 pg/kg/d (shrimp from North America). Results from the present
      study were comparable to other studies conducted recently and demonstrate that
      exposure to PCBs from consumption of farm-raised and wild-caught shrimp imported
      from different regions are not likely to pose any health risks.

PMID- 22407851
TI  - Copper-catalyzed di- and trifluoromethylation of alpha,beta-unsaturated
      carboxylic acids: a protocol for vinylic fluoroalkylations.
AB  - Dual action: the Lewis acid CuF(2) ?2 H(2)O efficiently catalyzes the reaction
      between electrophilic fluoroalkylating agents and alpha,beta-unsaturated
      carboxylic acids by dually activating both reactants, thus affording di- and
      trifluoromethyl alkenes in high yields with excellent E/Z selectivity.

PMID- 22407852
TI  - RAS mutations are frequent in FAB type M4 and M5 of acute myeloid leukemia, and
      related to late relapse: a study of the Japanese Childhood AML Cooperative Study
      Group.
AB  - Mutations in RAS are frequent in acute myeloid leukemia (AML), and are thought to
      contribute to leukemogenesis in a subset of patients; however, their prognostic
      significance has not been firmly established. One hundred and fifty-seven
      pediatric patients with AML were analyzed for NRAS and KRAS mutations around hot
      spots at codons 12, 13, and 61. Twenty-nine patients (18.5%) had an activating
      mutation of RAS. We found KRAS mutations to be more frequent than NRAS mutations
      (18/29, 62.1% of patients with RAS mutation), in contrast to previous reports (18
      40%). The frequency of RAS mutation was higher in French-American-British types
      M4 and M5 than other types (P = 0.02). There were no significant differences in
      other clinical manifestations or distribution in cytogenetic subgroups, or
      aberrations of other genes, including KIT mutation, FLT3-ITD, and MLL-PTD,
      between patients with and without RAS mutations. No significant differences were
      observed in the 3-year overall survival and disease-free survival; however, the
      presence of RAS mutation was related to late relapse. The occurrence of clinical
      events at relatively late period should be monitored for in AML patients with
      mutations in RAS.

PMID- 22407853
TI  - Quantification of PML/RARa transcript after induction predicts outcome in
      children with acute promyelocytic leukemia.
AB  - Reports on the use of the real-time quantitative polymerase chain reaction (RQ
      PCR) for childhood acute promyelocytic leukemia (APL) therapy are scarce. This
      study describes the prognostic significance of quantification of the PML-RARa
      transcript in children with APL. Since January 2004, we have analyzed 40 children
      treated with all-trans-retinoic acid +/- arsenic trioxide in induction. Thirty
      nine patients (97.5%) entered complete remission. The 5-year rates of disease
      free survival (DFS) and overall survival in these patients were 73.1 and 91.4%,
      respectively. By employing a standardized RQ-PCR protocol for minimal residual
      disease (MRD) monitoring, we determined that less than 1 normalized copy number
      (NCN) after induction indicates higher probability of a more favorable treatment
      outcome. After induction therapy, thirteen out of 38 (34.2%) patients in
      hematologic remission showed a negative RQ-PCR result (less than 1 NCN), which
      was correlated with the lower probability of relapse (100 and 55.2% DFS at 5
      years in the negative and positive RQ-PCR groups, respectively; P = 0.018).
      PML/RARa-based MRD monitoring by RQ-PCR may allow us to identify subgroups of
      patients at low risk of relapse after induction.

PMID- 22407854
TI  - Splenic infarction, warm autoimmune hemolytic anemia and antiphospholipid
      antibodies in a patient with infectious mononucleosis.
AB  - An 18-year-old woman with infectious mononucleosis developed splenic infarction
      and severe anemia. Evaluation of her anemia revealed a warm autoantibody and a
      persistently prolonged partial thromboplastin time that ultimately led to the
      identification of antiphospholipid antibodies. Although the warm autoantibody
      disappeared after 2 months, the antiphospholipid antibodies remained persistently
      positive. To our knowledge, this is the first case report in the literature of
      this specific constellation of findings, with infectious mononucleosis, warm
      antibody hemolytic anemia, splenic infarction and persistently positive, high
      titer antiphospholipid antibodies occurring in an individual patient.

PMID- 22407855
TI  - Epigenetics: Concepts and relevance to IBD pathogenesis.
AB  - The purpose of this review is to introduce the exciting field of epigenetics and
      to describe how it could explain the mechanisms by which environmental changes
      induce pathological gene expression and determine cell phenotype and function in
      IBD. We outline how epigenetics research in the context of a variety of clinical
      conditions, but mainly in cancer, has begun to define the role of multiple
      combinations of modifications to chromatin, diverse families of enzymes, and non
      coding RNAs in determining transcriptional outcomes. These findings are
      applicable to understanding the context-specific events that underlie the
      expression of genes in diseases like IBD and have the potential to reveal new
      targets for improved IBD therapy. The current status of epigenetics-based
      therapies is also summarized.

PMID- 22407856
TI  - Maternal care in the African striped mouse Rhabdomys pumilio: a behaviorally
      flexible phenotype that is modified by experience.
AB  - The development of maternal care in mammals can be influenced by the type and
      quality of maternal care received. Using biparental striped mice Rhabdomys
      pumilio, we investigated whether development of maternal care is influenced by
      the mother during early rearing and by an adult female's experience and that of
      her mate. Offspring were raised in one of three treatments, by: both parents;
      mothers alone; and mothers separated from the father with a barrier. Since female
      striped mice increase their care when raising litters alone, which influences
      expression of parental care of their adult sons, we expected daughters to respond
      like sons. However, there was no treatment effect in the development of maternal
      care in daughters. In subsequent experiments, experienced and inexperienced
      females decreased care when raising their offspring with experienced but not
      inexperienced males. Therefore, maternal care in striped mice is modulated in
      response to prevailing environmental and social conditions.

PMID- 22407857
TI  - Hepatic activation of IKK/NFkappaB signaling induces liver fibrosis via
      macrophage-mediated chronic inflammation.
AB  - Liver damage in humans is induced by various insults including alcohol abuse,
      hepatitis B/C virus infection, autoimmune or metabolic disorders and, when
      persistent, leads to development of liver fibrosis. Because the nuclear factor
      kappaB (NF-kappaB) system is activated in response to several of these stresses,
      we hypothesized that NF-kappaB activation in hepatocytes may contribute to
      fibrosis development. To activate the NF-kappaB signaling pathway in a time- and
      cell-type-specific manner in the liver, we crossed transgenic mice carrying the
      tetracycline-responsive transactivator under the control of the liver activator
      protein promotor with transgenic mice carrying a constitutively active form of
      the Ikbkb gene (IKK2 protein [CAIKK2]). Double-transgenic mice displayed
      doxycycline-regulated CAIKK2 expression in hepatocytes. Removal of doxycycline at
      birth led to activation of NF-kappaB signaling, moderate liver damage,
      recruitment of inflammatory cells, hepatocyte proliferation, and ultimately to
      spontaneous liver fibrosis development. Microarray analysis revealed prominent up
      regulation of chemokines and chemokine receptors and this induction was rapidly
      reversed after switching off the CAIKK2 expression. Turning off the transgene
      expression for 3 weeks reversed stellate cell activation but did not diminish
      liver fibrosis. The elimination of macrophages by clodronate-liposomes attenuated
      NF-kappaB-induced liver fibrosis in a liver-injury-independent manner.
      CONCLUSION: Our results revealed that hepatic activation of IKK/NF-kappaB is
      sufficient to induce liver fibrosis by way of macrophage-mediated chronic
      inflammation. Therefore, agents controlling the hepatic NF-kappaB system
      represent attractive therapeutic tools to prevent fibrosis development in
      multiple chronic liver diseases.

PMID- 22407858
TI  - Diagnostic accuracy of point-of-care fecal calprotectin and immunochemical occult
      blood tests for diagnosis of organic bowel disease in primary care: the Cost
      Effectiveness of a Decision Rule for Abdominal Complaints in Primary Care (CEDAR)
      study.
AB  - BACKGROUND: Fecal biomarker tests that differentiate between organic bowel
      disease (OBD) and non-OBD in primary care patients with persistent lower-abdomen
      complaints could reduce the number of unnecessary referrals for endoscopy. We
      quantified the accuracy of fecal calprotectin and immunochemical occult blood
      (iFOBT) point-of-care (POC) tests and a calprotectin ELISA in primary care
      patients with suspected OBD. METHODS: We performed biomarker tests on fecal
      samples from 386 patients with lower-abdomen complaints suggestive for OBD.
      Endoscopic and histological diagnosis served as reference. RESULTS: OBD was
      diagnosed in 99 patients (prevalence 25.9%); 19 had adenocarcinoma, 53 adenoma,
      and 27 inflammatory bowel disease. Sensitivity for OBD was 0.64 (95% CI 0.54
      0.72) for calprotectin POC, 0.56 (0.46-0.66) for iFOBT POC, and 0.74 (0.65-0.82)
      for calprotectin ELISA; specificities were 0.53 (0.48-0.59), 0.83 (0.78-0.87),
      and 0.47 (0.41-0.53), respectively. Negative predictive values (NPVs) were 0.81
      (0.74-0.86), 0.85 (0.80-0.88), and 0.84 (0.78-0.89); positive predictive values
      (PPVs) varied from 0.32 (0.26-0.39) and 0.33 (0.27-0.39) (calprotectin tests) to
      0.53 (0.44-0.63) (iFOBT POC). Combining the 2 POC tests improved sensitivity
      [0.79 (0.69-0.86)] and NPV [0.87 (0.81-0.91)] but lowered specificity [0.49 (0.44
      0.55)] and PPV [0.35 (0.29-0.42)]. When adenomas <=1 cm were considered non-OBD,
      the NPV of all tests improved to >0.90 [combined POC tests, 0.97 (0.93-0.99)].
      CONCLUSIONS: Diagnostic accuracy of the tests alone or combined was insufficient
      when all adenomas were considered OBD. When only adenomas >1 cm were considered
      OBD, all tests could rule out OBD to a reasonable extent, particularly the
      combined POC tests. The tests were less useful for inclusion of OBD.

PMID- 22407859
TI  - Maternal smoking during pregnancy and offspring trajectories of height and
      adiposity: comparing maternal and paternal associations.
AB  - BACKGROUND: Maternal smoking during pregnancy is associated with reduced
      offspring birth length and has been postulated as a risk factor for obesity.
      Causality for obesity is not established. Causality is well-supported for birth
      length, but evidence on persistence of height deficits is inconsistent. METHODS:
      We examined the association between maternal smoking during pregnancy and
      trajectories of offspring height (0-10 years, N = 9424), ponderal index (PI) (0-2
      years, N = 9321) and body mass index (BMI) (2-10 years, N = 8887) in the Avon
      Longitudinal Study of Parents and Children. To strengthen inference, measured
      confounders were controlled for, maternal and partner smoking associations were
      compared, dose-response and associations with post-natal smoking were examined.
      RESULTS: Maternal smoking during pregnancy was associated with shorter birth
      length, faster height growth in infancy and slower growth in later childhood. By
      10 years, daughters of women who smoke during pregnancy are on average 1.11 cm
      (SE = 0.27) shorter after adjustment for confounders and partner smoking; the
      difference is 0.22 cm (SE = 0.22) for partner's smoking. Maternal smoking was
      associated with lower PI at birth, faster PI increase in infancy, but not with
      BMI changes 2-10 years. Associations were stronger for maternal than partner
      smoking for PI at birth and PI changes in infancy, but not for BMI changes after
      2 years. A similar dose-response in both maternal and partner smoking was seen
      for BMI change 2-10 years. CONCLUSION: Maternal smoking during pregnancy has an
      intrauterine effect on birth length, and possibly on adiposity at birth and
      changes in height and adiposity in infancy. We do not find evidence of a specific
      intrauterine effect on height or adiposity changes after the age of 2 years.

PMID- 22407861
TI  - Commentary: obesity and mortality in China: the shape of things to come.

PMID- 22407860
TI  - Epidemiology in Latin America and the Caribbean: current situation and
      challenges.
AB  - BACKGROUND: This article analyses the epidemiological research developments in
      Latin America and the Caribbean (LAC). It integrates the series commissioned by
      the International Epidemiological Association to all WHO Regions to identify
      global opportunities to promote the development of epidemiology. METHODS: Health
      situations of the regions were analysed based on published data on selected
      mortality, morbidity and risk factors. Epidemiological publication output by
      country was estimated by Medline bibliometrics. Internet and literature searches
      and data provided by key informants were used to describe perspectives on
      epidemiological training, research and funding. FINDINGS: Despite important
      advances in recent decades, LAC remains the world's most unequal region. In 2010,
      10% of the LAC's people still lived in conditions of multidimensional poverty,
      with huge variation among countries. The region has experienced fast and complex
      epidemiological changes in past decades, combining increasing rates of non
      communicable diseases and injuries, and keeping uncontrolled many existing
      endemic and emerging diseases. Overall, epidemiological publications per year
      increased from 160 articles between 1961 and 1970 to 2492 between 2001 and 2010.
      The increase in papers per million inhabitants in the past three decades varied
      from 57% in Panama to 1339% in Paraguay. Universities are the main
      epidemiological training providers. There are at least 34 universities and other
      institutions in the region that offer postgraduate programmes at the master's and
      doctoral levels in epidemiology or public health. Most LAC countries rely largely
      on external funding and donors to initiate and sustain long-term research
      efforts. Despite the limited resources, the critical mass of LAC researchers has
      produced significant scientific contributions. FUTURE NEEDS: The health research
      panorama of the region shows enormous regional discrepancies, but great
      prospects. Improving research and human resources capacity in the region will
      require establishing research partnerships within and outside the region, between
      rich and poor countries, promoting collaborations between LAC research
      institutions and universities to boost postgraduate programmes and aligning
      research investments and outputs with the current burden of disease.

PMID- 22407862
TI  - Burden of disease, health indicators and challenges for epidemiology in North
      America.
AB  - BACKGROUND: Commissioned by the International Epidemiological Association, this
      article is part of a series on burden of disease, health indicators and the
      challenges faced by epidemiologists in bringing their discoveries to provide
      equitable benefit to the populations in their regions and globally. This report
      covers the health status and epidemiological capacity in the North American
      region (USA and Canada). METHODS: We assessed data from country-specific sources
      to identify health priorities and areas of greatest need for modifiable risk
      factors. We examined inequalities in health as a function of social deprivation.
      We also reviewed information on epidemiological capacity building and scientific
      contributions by epidemiologists in the region. FINDINGS: The USA and Canada
      enjoy technologically advanced healthcare systems that, in principle, prioritize
      preventive services. Both countries experience a life expectancy at birth that is
      higher than the global mean. Health indicator measures are consistently worse in
      the USA than in Canada for many outcomes, although typically by only marginal
      amounts. Socio-economic and racial/ethnic disparities in indicators exist for
      many diseases and risk factors in the USA. To a lesser extent, these social
      inequalities also exist in Canada, particularly among the Aboriginal populations.
      Epidemiology is a well-established discipline in the region, with many degree
      granting schools, societies and job opportunities in the public and private
      sectors. North American epidemiologists have made important contributions in
      disease control and prevention and provide nearly a third of the global
      scientific output via published papers. CONCLUSIONS: Critical challenges for
      North American epidemiologists include social determinants of disease
      distribution and the underlying inequalities in access to and benefit from
      preventive services and healthcare, particularly in the USA. The gains in life
      expectancy also underscore the need for research on health promotion and
      prevention of disease and disability in older adults. The diversity in
      epidemiological subspecialties poses new challenges in training and accreditation
      and has occurred in parallel with a decrease in research funding.

PMID- 22407863
TI  - Reversible phase transformation and mechanochromic luminescence of Zn(II)
      dipyridylamide-based coordination frameworks.
AB  - A 1D double-zigzag framework, {[Zn(paps)(2)(H(2)O)(2)](ClO(4))(2)}(n) (1; paps =
      N,N'-bis(pyridylcarbonyl)-4,4'-diaminodiphenyl thioether), was synthesized by the
      reaction of Zn(ClO(4))(2) with paps. However, a similar reaction, except that dry
      solvents were used, led to the formation of a novel 2D polyrotaxane framework,
      [Zn(paps)(2)(ClO(4))(2)](n) (2). This difference relies on the fact that water
      coordinates to the Zn(II) ion in 1, but ClO(4)(-) ion coordination is found in 2.
      Notably, the structures can be interconverted by heating and grinding in the
      presence of moisture, and such a structural transformation can also be proven
      experimentally by powder and single-crystal X-ray diffraction studies. The
      related N,N'-bis- (pyridylcarbonyl)-4,4'-diaminodiphenyl ether (papo) and N,N'
      (methylenedi-para-phenylene)bispyridine-4-carboxamide (papc) ligands were reacted
      with Zn(II) ions as well. When a similar reaction was performed with dry
      solvents, except that papo was used instead of paps, the product mixture
      contained mononuclear [Zn(papo)(CH(3)OH)(4)](ClO(4))(2) (5) and the polyrotaxane
      [Zn(papo)(2)(ClO(4))(2)](n) (4). From the powder XRD data, grinding this mixture
      in the presence of moisture resulted in total conversion to the pure double
      zigzag {[Zn(papo)(2)(H(2)O)(2)](ClO(4))(2)}(n) (3) immediately. Upon heating 3,
      the polyrotaxane framework of 4 was recovered. The double-zigzag
      {[Zn(papc)(2)(H(2)O)(2)](ClO(4))(2)}(n) (6) and polyrotaxane
      [Zn(papc)(2)(ClO(4))(2)](n) (7) were synthesized in a similar reaction. Although
      upon heating the double-zigzag 6 undergoes structural transformation to give the
      polyrotaxane 7, grinding solid 7 in the presence of moisture does not lead to the
      formation of 6. Significantly, the bright emissions for double-zigzag frameworks
      of 1 and 3 and weak ones for polyrotaxane frameworks of 2 and 4 also show
      interesting mechanochromic luminescence.

PMID- 22407864
TI  - Inhibition of neutrophil elastase and metalloprotease-9 of human adenocarcinoma
      gastric cells by chamomile (Matricaria recutita L.) infusion.
AB  - This study investigated whether the antiinflammatory effect of chamomile infusion
      at gastric level could be ascribed to the inhibition of metalloproteinase-9 and
      elastase. The infusions from capitula and sifted flowers (250-1500 ug/mL) and
      individual flavonoids (10 uM) were tested on phorbol 12-myristate 13-acetate
      stimulated AGS cells and human neutrophil elastase. The results indicate that the
      antiinflammatory activity associated with chamomile infusions from both the
      capitula and sifted flowers is most likely due to the inhibition of neutrophil
      elastase and gastric metalloproteinase-9 activity and secretion; the inhibition
      occurring in a concentration dependent manner. The promoter activity was
      inhibited as well and the decrease of metalloproteinase-9 expression was found to
      be associated with the inhibition of NF-kB driven transcription. The results
      further indicate that the flavonoid-7-glycosides, major constituents of chamomile
      flowers, may be responsible for the antiinflammatory action of the chamomile
      infusion observed here.

PMID- 22407865
TI  - Latent learning of spatial information is impaired in middle-aged rats.
AB  - The present study determined if the middle age related impairment that occurs
      with nonspatial latent learning also occurs in spatial latent learning. Thirty
      young (3-months-old) and 30 middle-aged (12-months-old) male Sprague-Dawley rats
      were given either pre-exposure to spatial cues surrounding a Barnes maze
      (SpatialPX), or pre-exposure to just the maze (MazePX). They were then given 10
      training trials in which they had to find a hidden escape box while experiencing
      an aversive environment produced by bright lights and wind. Results showed that
      young rats given the SpatialPX condition demonstrated faster escape latencies and
      fewer errors than young rats given the MazePX condition. However, middle-aged
      rats given the SpatialPX condition did not show this improved performance. These
      findings indicate that the middle age learning deficit is not task specific, but
      rather is a general impairment in latent learning, possibly due to the early
      degeneration of the entorhinal cortex.

PMID- 22407866
TI  - Male sex bias in placental dysfunction.
AB  - Several reports suggest a male fetal preponderance in a variety of complications
      of pregnancy attributable to severe placental dysfunction (SPD). However, the
      underlying mechanisms remain unknown. Our primary objective was to explore the
      relationship between fetal sex and the spectrum of conditions implicated in
      abnormal placentation. We identified singleton pregnancies with a fetus delivered
      between 20 + 0 and 32 + 6 weeks of gestation with one or more pregnancy
      complications attributed to SPD (severe pre-eclampsia, intra-uterine fetal death,
      intra-uterine growth restriction, abnormal Doppler studies, abruption) at a
      single institution between 1999 and 2007. Pedigrees of index cases were created
      to define the relationship between fetal sex and the risk of SPD. We identified
      132 index cases, 97/132 (73%) were male. Eighty-four index cases had a total of
      133 sibs, of which 37/133 (28%) were affected with SPD (22 male, 15 female). A
      male sex preponderance persisted across all manifestations of PD in index cases
      with sibs. In families with the absence of maternal chronic hypertension (cHTN; n
      = 70), the index case was 5.9 (95% CI 2.28-16.15; P <0.001) times more likely to
      be male and most (12/14) affected sibs of male index cases were male, while
      female index cases had no affected sibs. Our results confirm a male fetal sex
      preponderance in SPD. In a subgroup analysis of families without cHTN, a
      significant male bias was found to extend to sibs of index cases. This suggests a
      potential genetic mechanism predisposing the male fetus to abnormal placental
      development.

PMID- 22407867
TI  - The clinician administered staging instrument for anorexia nervosa: development
      and psychometric properties.
AB  - OBJECTIVE: To develop and evaluate an instrument to assess severity in anorexia
      nervosa (AN), the Clinician Administered Staging Instrument for Anorexia Nervosa
      (CASIAN). METHOD: Candidate items for the CASIAN were developed in three phases
      (domain, content, and item generation) followed by a pilot study. The
      psychometric properties of the resultant 34-item questionnaire were investigated
      in cross-sectional and longitudinal samples (N = 171) with DSM-IV AN and
      subthreshold AN. RESULTS: Item and factor analysis procedures resulted in a
      refined 23-item CASIAN comprising of six factors ("Motivation," "Weight,"
      "Illness Duration," "Obsessionality," "Bulimic Behaviors," and "Acute Issues").
      The CASIAN had high internal consistency (.811), test-retest (.957), and
      interrater reliability (.973). Preliminary support for the convergent,
      discriminant, concurrent, and predictive validity of the CASIAN was found.
      DISCUSSION: The CASIAN is a psychometrically sound instrument. Further studies
      are needed to confirm the factor structure and assess its clinical and research
      utility.

PMID- 22407868
TI  - A case of anorexia nervosa with disseminated intravascular coagulation syndrome.
AB  - A 36-year-old Japanese woman with anorexia nervosa (AN) was admitted to our
      department because of severe emaciation. Although we were thorough in her
      clinical management and were careful to avoid precipitating refeeding syndrome,
      disseminated intravascular coagulation (DIC) developed 3 weeks after
      hospitalization. We treated her for DIC with sepsis using anticoagulants,
      protease inhibitors, antithrombin, and platelet concentrate transfusion. To treat
      her bacterial infection, we administered antimicrobial drugs and immunoglobulin.
      We began probiotic and prebiotic (synbiotics) treatment for bacterial
      translocation. We think that the prevention of sepsis via bacterial translocation
      is an important aspect of care for patients with severe AN in addition to the
      prevention of refeeding syndrome.

PMID- 22407869
TI  - Differential tolerance of native and nonnative fish exposed to ultraviolet
      radiation and fluoranthene in Lake Tahoe (California/Nevada), USA.
AB  - Within Lake Tahoe (CA/NV), USA, multiple environmental stressors are present that
      can affect both native and nonnative fish species. Stressors include natural
      ultraviolet radiation (UVR) and polycyclic aromatic hydrocarbons (PAHs). Many
      PAHs, such as fluoranthene (FLU) are phototoxic to aquatic organisms in the
      presence of UVR. Decreasing levels of UVR due to eutrophication and increasing
      levels of PAHs due to recreational activities may combine to affect the relative
      ability of native versus nonnative fish species to survive in the lake. The
      objective of the present study was to examine the differential effects of
      exposure to different levels of UVR and phototoxic FLU in native and nonnative
      fish species. Responses to these changes in the native Lahontan redside minnow
      (Richardsonius egregius) and the nonnative warm-water bluegill sunfish (Lepomis
      macrochirus) were compared during toxicity tests, which were conducted in
      controlled outdoor exposures. Physiological defenses were also investigated in an
      attempt to elucidate ways each species may tolerate UVR and UVR + FLU exposures.
      It was determined that the native redside minnow is more tolerant to UVR and UVR
      + FLU exposure when compared to the nonnative bluegill. In addition, a natural
      UVR coping mechanism, increased pigmentation, is exhibited to a greater extent in
      the native redside. The present study will help determine the potential for a
      future successful invasion of the bluegill and similar species in Lake Tahoe and
      other oligotrophic, montane lakes that are susceptible to habitat alteration,
      nutrient inputs, and recreational activity.

PMID- 22407870
TI  - Is a change in vocal loudness a first step towards becoming a medical doctor?
AB  - QUESTIONS UNDER STUDY: Some evidence suggests that a loud voice is a core
      characteristic of medical professionals. It is unknown whether medical students
      talk louder than their non-medical peers and, if so, whether they commence their
      studies with a loud voice, representing a characteristic of admission, or whether
      sound pressure level changes during education, reflecting model learning.
      METHODS: We performed a cross-sectional observation study with 206 students (57%
      female), stratified in 4 groups (medical and non-medical students as freshmen and
      fifth-year students). Habitual loudness was defined as a student's sound pressure
      level, measured with a standardised sound level meter on basis of 2 vocal tasks.
      The hypothesis was tested in a 2-way analysis of variance, with year of study
      (first vs. fifth year) and field by study (medicine vs. non-medicine) as main
      factors. RESULTS: The sound pressure level of freshmen in medicine was, on
      average, 64.4 dB (SD 3.0), that of fifth-year medical students was 66.3 dB (3.7).
      The respective scores of non-medical students were 65.3 (SD 2.7) for freshmen and
      64.0 (3.4) for fifth-year students, resulting in a significant interaction
      between field of study and years of study (F = 12.7; p = 0.0005). CONCLUSIONS:
      The findings of this preliminary study present some evidence that medical
      students, in contrast to their non-medical peers, learn to raise vocal loudness
      during their education in medical school. Habitual loudness of medical students,
      as a way to gain professional dominance and a possible risk for hoarseness in
      later life, deserves more attention.

PMID- 22407871
TI  - Organic food quality: a framework for concept, definition and evaluation from the
      European perspective.
AB  - Consumers buy organic food because they believe in the high quality of the
      product. Furthermore, the EU legal regulatory framework for organic food and
      farming defines high quality of the products as an important goal of production.
      A major challenge is the need to define food quality concepts and methods for
      determination. A background is described which allows embedding of the quality
      definitions as well as evaluation methods into a conceptual framework connected
      to the vision and mission of organic agriculture and food production. Organic
      food quality is defined through specific aspects and criteria. For evaluation
      each criterion has to be described by indicators. The determination of indicators
      should be through parameters, where parameters are described by methods.
      Conversely, the conceptual framework is described according to underlying
      principles and starting definitions are given, but further work has do be done on
      the detailed scientific description of the indicators. Furthermore, parameters
      have to be defined for the evaluation of suitability of these indicators for
      organic food production.

PMID- 22407872
TI  - A caspase 8-based suicide switch induces apoptosis in nanobody-directed chimeric
      receptor expressing T cells.
AB  - In accordance with the two-step hypothesis of T cell activation and the
      observation that stimulation through the T cell receptor (TCR) alone may lead to
      anergy, we focused on the introduction of co-stimulatory signaling to this type
      of receptors to achieve optimal activation. Enhanced mRNA and cell surface
      receptor expression via the co-stimulatory gene fragment (OX40) was confirmed by
      RT-PCR and flow cytometry. Inclusion of the OX40 co-stimulatory signaling region
      in series with the TCR led to enhanced antigen-induced IL-2 production after
      stimulation by MUC1-expressing cancer cell lines as compared to the chimeric
      receptor without OX40. Moreover, with the aim of maintaining high efficiency,
      while providing a means of controlling any possible unwanted proliferation in
      vivo, a regulation system was used. This controls the dimerization of a membrane
      bound caspase 8 protein. Toward that goal, pFKC8 and CAR constructs were co
      transfected into Jurkat cells, and the level of apoptosis was measured. 24 h
      after addition of the dimerizer, a 91% decrease in transfected cells was
      observed.

PMID- 22407873
TI  - Prognostic significance of serum ferritin level at diagnosis in myelodysplastic
      syndrome.
AB  - Myelodysplastic syndrome (MDS) is characterized by peripheral blood cytopenias
      and risk of progression to acute myeloid leukemia. Elevated serum ferritin (SF),
      due to ineffective erythropoiesis and increased iron absorption from the gut, is
      often observed in non-transfused MDS patients, suggesting involvement of iron
      overload in its pathogenesis. However, the prognostic value of the baseline SF is
      unclear. We evaluated baseline SF levels in non-transfused MDS patients. The SF
      level was significantly higher in the 47 MDS patients in this study than in the
      healthy controls (P < 0.001). The SF level of higher-risk MDS patients (int
      2/high) was significantly higher than that of the lower-risk MDS patients
      (low/int-1) (467 +/- 354 vs. 277 +/- 372 ng/ml, P < 0.001). The SF level in MDS
      patients with chromosomal abnormality was significantly higher than that in
      patients with normal karyotype. When patients were divided into the low SF group
      (<500 ng/ml) and high SF group (>=500 ng/mL), the survival time was significantly
      longer in the former group than the latter group (118.8 vs. 10.2 M, P = 0.002).
      Further, leukemia-free survival (LFS) was significantly longer in the low SF
      group than the high SF group (P = 0.010). Baseline SF level may, therefore, be a
      prognostic factor for overall survival and LFS in MDS patients.

PMID- 22407874
TI  - Plasmonic nanobubbles enhance efficacy and selectivity of chemotherapy against
      drug-resistant cancer cells.

PMID- 22407875
TI  - New insights into the biological and synthetic fixation of nitrogen.

PMID- 22407876
TI  - High serum adiponectin predicts incident fractures in elderly men: Osteoporotic
      fractures in men (MrOS) Sweden.
AB  - Adipocytes and osteoblasts share a common progenitor, and there is, therefore,
      potential for both autocrine and endocrine effects of adiponectin on skeletal
      metabolism. The aim of the present study was to determine whether high serum
      adiponectin was associated with an increased risk of fracture in elderly men. We
      studied the relationship between serum adiponectin and the risk of fracture in
      999 elderly men drawn from the general population and recruited to the
      Osteoporotic Fractures in Men (MrOS) study in Gothenburg, Sweden. Baseline data
      included general health questionnaires, lifestyle questionnaires, body mass index
      (BMI), bone mineral density (BMD), serum adiponectin, osteocalcin, and leptin.
      Men were followed for up to 7.4 years (average, 5.2 years). Poisson regression
      was used to investigate the relationship between serum adiponectin, other risk
      variables and the time-to-event hazard function of fracture. Median levels of
      serum adiponectin at baseline were 10.4 ug/mL (interquartile range, 7.7-14.3).
      During follow-up, 150 men sustained one or more fractures. The risk of fracture
      increased in parallel with increasing serum adiponectin (hazard ratio [HR]/SD,
      1.46; 95% confidence interval [CI], 1.23-1.72) and persisted after multivariate
      adjusted analysis (HR/SD, 1.30; 95% CI, 1.09-1.55). Serum adiponectin shows
      graded stepwise association with a significant excess risk of fracture in elderly
      men that was independent of several other risk factors for fracture. Its
      measurement holds promise as a risk factor for fracture in men.

PMID- 22407877
TI  - S(N)1-type substitution reactions of N-protected beta-hydroxytyrosine esters:
      stereoselective synthesis of beta-aryl and beta-alkyltyrosines.
AB  - The title compounds were prepared by aldol reaction of anisaldehyde and the
      respective N,N-dibenzyl glycinates. Deprotection of the nitrogen atom with
      Pearlman's catalyst delivered the unprotected beta-hydroxytyrosine esters, which
      were further N-protected as N,N-phthaloyl (Phth) and N-fluorenylmethylcarbonyloxy
      (Fmoc) derivatives. The Friedel-Crafts reaction with various arenes was studied
      employing these alcohols as electrophiles. It turned out that the facial
      diastereoselectivitiy depends on the nitrogen protecting group and on the ester
      group. The unprotected substrates (NH(2)) gave preferentially syn-products but
      the anti-selectivity increased when going from NHFmoc over NPhth to NBn(2). If
      the ester substituent was varied the syn-preference increased in the order Me <
      Et < iPr. The reactions were shown to be fully stereoconvergent and proceeded
      under kinetic product control. A model is suggested to explain the facial
      diastereoselectivity based on a conformationally locked benzylic cation
      intermediate. The reactions are preparatively useful for the N-unprotected
      isopropyl ester, which gave Friedel-Crafts alkylation products with good syn
      selectivity (anti/syn=21:79 to 7:93), and for the N,N-dibenzyl-protected methyl
      ester, which led preferentially to anti-products (anti/syn=80:20 to >95:5). Upon
      acetylation of the latter compound to the respective acetate, Bi(OTf)(3) 
      catalyzed alkylation reactions became possible, in which silyl enol ethers served
      as nucleophiles. The respective alkylation products were obtained in high yield
      and with excellent anti-selectivitiy (anti/syn>=95:5).

PMID- 22407878
TI  - Early bedside detection of ischemia and rejection in liver transplants by
      microdialysis.
AB  - This study was performed to explore whether lactate, pyruvate, glucose, and
      glycerol levels sampled via microdialysis catheters in the transplanted liver
      could be used to detect ischemia and/or rejection. The metabolites were measured
      at the bedside every 1 to 2 hours after the operation for a median of 10 days.
      Twelve grafts with biopsy-proven rejection and 9 grafts with ischemia were
      compared to a reference group of 39 grafts with uneventful courses. The median
      lactate level was significantly higher in both the ischemia group [5.8 mM
      (interquartile range = 4.0-11.1 mM)] and the rejection group [2.1 mM
      (interquartile range = 1.9-2.4 mM)] versus the reference group [1.5 mM
      (interquartile range = 1.1-1.9 mM), P < 0.001 for both]. The median pyruvate
      level was significantly increased only in the rejection group [185 MUM
      (interquartile range = 155-206 MUM)] versus the reference group [124 MUM
      (interquartile range = 102-150 MUM), P < 0.001], whereas the median
      lactate/pyruvate ratio and the median glycerol level were increased only in the
      ischemia group [66.1 (interquartile range = 23.9-156.7) and 138 MUM
      (interquartile range = 26-260 MUM)] versus the reference group [11.8
      (interquartile range = 10.6-13.6), P < 0.001, and 9 MUM (interquartile range = 9
      24 MUM), P = 0.002]. Ischemia was detected with 100% sensitivity and greater than
      90% specificity when a positive test was repeated after 1 hour. In 3 cases of
      hepatic artery thrombosis, ischemia was detected despite normal blood lactate
      levels. Consecutive pathological measurements for 6 hours were used to diagnose
      rejection with greater than 80% sensitivity and specificity at a median of 4 days
      before the activity of alanine aminotransferase, the concentration of bilirubin
      in serum, or both increased. In conclusion, bedside measurements of intrahepatic
      lactate and pyruvate levels were used to detect ischemia and rejection earlier
      than current standard methods could. Discrimination from an uneventful patient
      course was achieved. Consequently, intrahepatic graft monitoring with
      microdialysis may lead to the earlier initiation of graft-saving treatment.

PMID- 22407879
TI  - Family conflict among Chinese- and Mexican-origin adolescents and their parents
      in the U.S.: an introduction.
AB  - This volume explores how cultural and family contexts inform parent-adolescent
      conflict and adjustment among Chinese- and Mexican-origin families in the United
      States. Collectively, the chapters examine outcomes associated with family
      conflict and provide an in-depth analysis of how and for whom conflict is related
      to adjustment. Findings, for example, illustrate how cultural factors (e.g.,
      acculturation) modify the links between conflict and adjustment. Furthermore, the
      collection allows for a simultaneous examination of normative, everyday parent
      adolescent conflict and conflict that is specific to the process of cultural
      adaptation, and furthers our understanding of how both developmental and cultural
      sources of conflict are linked to adjustment.

PMID- 22407881
TI  - Conflicts and communication between high-achieving Chinese American adolescents
      and their parents.
AB  - Drawing on in-depth interview data collected on 18 high-achieving Chinese
      American students, the authors examine domains of acculturation-based conflicts,
      parent and child internal conflicts, and conflict resolution in their families.
      Their analyses show that well-established negative communication patterns in
      educational expectations, divergent attitudes toward other races and country of
      origin, and cultural and language barriers contributed to parent-child conflicts.
      Their findings also illustrate important internal conflicts both adolescents and
      parents had along the cultural tightrope of autonomy and relatedness. Finally,
      the vertical in-group conflict resolution style that was evidenced in youths'
      accounts raises questions about cultural differences in constructive versus
      destructive conflict resolution styles.

PMID- 22407880
TI  - Acculturation-based and everyday family conflict in Chinese American families.
AB  - Everyday conflict (studied primarily among European American families) is viewed
      as an assertion of autonomy from parents that is normative during adolescence.
      Acculturation-based conflict (studied primarily among Asian- and Latino-heritage
      families) is viewed as a threat to relatedness with parents rather than the
      normative assertion of autonomy. Our overarching goal for the chapter is to
      integrate our knowledge of these two types of family conflict that have been
      studied separately to arrive at a new understanding of what family conflict means
      for Chinese American adolescents and their parents.

PMID- 22407882
TI  - Mother-daughter conflict and adjustment in Mexican-origin families: exploring the
      role of family and sociocultural context.
AB  - This study examined the role of mother-daughter conflict in both mothers' and
      daughters' adjustment. Drawing from ecologically oriented and person-environment
      fit models, the authors investigated how the family context, as defined by the
      transition to adolescent motherhood, and the sociocultural context, as measured
      by mother-daughter discrepancies in cultural orientations, shaped the
      associations between conflict and adjustment in Mexican-origin families. Overall,
      conflict was positively related to mothers' and adolescents' depressive symptoms
      and adolescents' risky behaviors. This relation was strongest when daughters were
      more Mexican-oriented than their mothers, and weakest when mothers were more
      Mexican-oriented than their daughters.

PMID- 22407883
TI  - Guided cognitive reframing of adolescent-father conflict: who Mexican American
      and European American adolescents seek and why.
AB  - Adolescents may seek to understand family conflict by seeking out confidants.
      However, little is known about whom adolescents seek, whether and how such
      support helps youth, and the factors that predict which sources are sought. This
      chapter offers a conceptual model of guided cognitive reframing that emphasizes
      the behavioral, cognitive, and affective implications of confidant support as
      well as individual, family, and cultural factors linked to support seeking. The
      authors present empirical data from 392 families of seventh graders of Mexican
      and European ancestry to predict whether adolescents seek mothers, coresident
      fathers, and other sources and provide directions for subsequent research.

PMID- 22407884
TI  - Gaps, conflicts, and arguments between adolescents and their parents.
AB  - Parent-adolescent conflict appears to be similar across different immigrant
      generations and cultural groups in frequency and implications for adjustment.
      However, the same level of argumentation may mask hidden conflictual feelings
      that are not expressed. Why an acculturation gap leads to such conflictual
      feelings in some adolescents and not others is still not well understood.
      Addressing this and other important issues of parent-adolescent difference by
      clearly separating acculturation gaps, conflictual feelings, and actual arguments
      would go a long way toward helping us to understand the role of family
      relationships in the adaptation and adjustment of adolescents from Asian and
      Latin American backgrounds.

PMID- 22407885
TI  - Primary sclerosing cholangitis is associated with a distinct phenotype of
      inflammatory bowel disease.
AB  - BACKGROUND: Primary sclerosing cholangitis (PSC) is strongly associated with
      inflammatory bowel disease (IBD). The aim of this study was to assess the IBD
      phenotype associated with PSC in a large well-phenotyped population-based PSC
      cohort using endoscopic and histopathologic criteria. METHODS: PSC cases were
      identified and ascertained, fulfilling well-established criteria, in 39 hospitals
      in a geographically defined region of The Netherlands. IBD location was recorded
      according to the Montreal Classification. As this classification does not
      consider segmental inflammation, backwash ileitis, or rectal sparing, an
      additional subgroup analysis was performed in 80 cases and 80 age- and sex
      matched IBD controls, reviewing all endoscopy and pathology reports filed between
      2000 and 2010. RESULTS: In all, 380 (66%) of a total of 579 PSC patients had
      coexistent IBD, mainly ulcerative colitis (UC) (75%). Overall, 207 (83%) of the
      PSC-UC patients had a pancolitis, 32 (13%) a left-sided colitis, and 9 (4%) a
      proctitis only. Seventy (95%) PSC-Crohn's disease (CD) patients had an
      (ileo)colitis and four (5%) ileitis only. In the subgroup analysis 53 (66%) PSC
      UC patients were identified, 24 (30%) PSC-CD patients, and three (4%) PSC-IBD-U
      patients. Fifty (94%) PSC-UC patients had a pancolitis, compared with 32 (62%)
      matched UC patients (P < 0.001). Left-sided colitis was seen in 16 (31%) UC
      controls and in one PSC-UC patient (P < 0.001). Backwash ileitis and rectal
      sparing were rare findings (<10%) in the cohorts under study. CONCLUSIONS: IBD in
      PSC patients represents a distinct phenotype in that pancolitis is observed in
      94% of PSC-UC and colitis in 96% of PSC-CD patients. Backwash ileitis and rectal
      sparing were rare findings in the PSC-UC patients.

PMID- 22407886
TI  - Development and validation of a simple assay for the determination of
      cholinesterase activity in whole blood of laboratory animals.
AB  - Current methods for measuring acetylcholinesterase (AChE) activities in whole
      blood use butyrylcholinesterase (BChE)-selective inhibitors. However, the poor
      selectivity of these inhibitors results in the inhibition of AChE activity to
      some degree, leading to errors in reported values. The goal of this study was to
      develop and validate a simple assay for measuring AChE and BChE activities in
      whole blood from humans as well as experimental animals. Blood was fractionated
      into plasma and erythrocytes, and cholinesterase activities were titrated against
      ethopropazine and (-)-huperzine A to determine the lowest concentration of
      ethopropazine that inhibited BChE completely without affecting AChE activity and
      the lowest concentration of (-)-huperzine A that inhibited AChE completely
      without interfering with BChE activity. Results indicate that 20 um ethopropazine
      can be successfully used for the accurate measurement of AChE activity in blood
      from humans as well as animals. Use of (-)-huperzine A is not required for
      measuring BChE activity in normal or 'exposed' blood samples. The method was
      validated for blood from several animal species, including mice, rats, guinea
      pigs, dogs, minipigs, and African green, cynomolgus and rhesus monkeys. This
      method is superior to all reported methods, does not require the separation of
      erythrocyte and plasma fractions, and is suitable for measuring cholinesterase
      activities in fresh or frozen blood from animals that were exposed to nerve
      agents or those that were administered high doses of BChE. The method is simple,
      direct, reproducible, and reliable and can easily be adapted for high-throughput
      screening of blood samples. Published 2012. This article is a US Government work
      and is in the public domain in the USA.

PMID- 22407887
TI  - Replacement of bovine serum albumin with N-methyl-D-aspartic acid and
      homocysteine improves development, but not live birth.

PMID- 22407888
TI  - Factors mediating remote preconditioning of trauma in the rat heart: central role
      of the cytochrome p450 epoxygenase pathway in mediating infarct size reduction.
AB  - The present study further identified factors involved in the cardioprotective
      phenomenon of remote preconditioning of trauma (RPCT) with special emphasis on
      the role of the epoxyeicosatrienoic acids (EETs) in mediating this phenomenon.
      Remote preconditioning of trauma was produced by an abdominal incision only
      through the skin. Subsequently, all rats were subjected to 30 minutes of left
      coronary artery occlusion followed by 2 hours of reperfusion and the infarct size
      was determined. Remote preconditioning of trauma produced a reduction in infarct
      size expressed as a percentage of the area at risk from 63.0% +/- 1.1% to 44.7%
      +/- 1.4%; P < .01 versus control. To test the 3 major triggers of classical
      preconditioning in mediating RPCT, blockers of the bradykinin B2 receptor (B2BK),
      (S)-4-[2-[Bis(cyclohexylamino)methyleneamino]-3-(2-naphthalenyl)-1
      oxopropylamino]benzyl tributyl phosphonium (WIN 64338, 1 mg/kg, iv), or HOE 140
      (50 MUg/kg, iv), the nonselective opioid receptor blocker, naloxone (3 mg/kg,
      iv), or the adenosine A1 receptor blocker, 8-Cyclopentyl-1,3-dipropylxanthine
      (DPCPX, 1 mg/kg, iv) were administered 10 minutes prior to RPCT. Only the 2 B2BK
      selective antagonists blocked RPCT (60.2% +/- 1.1%, WIN 64338; 62.3% +/- 2.0%,
      HOE 140). To test EETs in RPCT, we administered the EET receptor antagonist 14,15
      Epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, 2.5 mg/kg, iv) or the EET synthesis
      inhibitor, N-(Methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MSPPOH, 3.0
      mg/kg, iv) 10 minutes prior to RPCT. In both groups, the EET antagonists
      completely blocked RPCT (62.0% +/- 0.8%, 14,15-EEZE; 61.8% +/- 1.0%, MSPPOH). The
      EET antagonists also blocked the effect of B2BK activation. We also determined
      whether the sarcolemmal K(ATP) or the mitochondrial K(ATP) channel mediate RPCT
      by pretreating rats with 1-[5-[2-(5-Chloro-o-anisamido)ethyl]-2
      methoxyphenyl]sulfonyl-3 methylthiourea, sodium salt (HMR 1098) or 5
      hydroxydecanoic acid (5-HD), respectively. Interestingly, 5-HD blocked RPCT
      (64.7% +/- 1.3%), whereas, HMR 1098 did not (50.3% +/- 1.3%). The 2 EET
      antagonists completely blocked capsaicin-induced cardioprotection. These results
      clearly suggest that EETs mediate RPCT-, bradykinin- and capsaicin-induced
      cardioprotection in rat hearts.

PMID- 22407889
TI  - Hot off the breath: 'I've a cost for'--the 64 million dollar question.

PMID- 22407891
TI  - Pulmonary complications of intravesicular BCG immunotherapy.

PMID- 22407890
TI  - Predictors of clinical outcome in a national hospitalised cohort across both
      waves of the influenza A/H1N1 pandemic 2009-2010 in the UK.
AB  - BACKGROUND: Although generally mild, the 2009-2010 influenza A/H1N1 pandemic
      caused two major surges in hospital admissions in the UK. The characteristics of
      patients admitted during successive waves are described. METHODS: Data were
      systematically obtained on 1520 patients admitted to 75 UK hospitals between May
      2009 and January 2010. Multivariable analyses identified factors predictive of
      severe outcome. RESULTS: Patients aged 5-54 years were over-represented compared
      with winter seasonal admissions for acute respiratory infection, as were non
      white ethnic groups (first wave only). In the second wave patients were less
      likely to be school age than in the first wave, but their condition was more
      likely to be severe on presentation to hospital and they were more likely to have
      delayed admission. Overall, 45% had comorbid conditions, 16.5% required high
      dependency (level 2) or critical (level 3) care and 5.3% died. As in 1918-1919,
      the likelihood of severe outcome by age followed a W-shaped distribution. Pre
      admission antiviral drug use decreased from 13.3% to 10% between the first and
      second waves (p=0.048), while antibiotic prescribing increased from 13.6% to
      21.6% (p<0.001). Independent predictors of severe outcome were age 55-64 years,
      chronic lung disease (non-asthma, non-chronic obstructive pulmonary disease),
      neurological disease, recorded obesity, delayed admission (>=5 days after illness
      onset), pneumonia, C-reactive protein >=100 mg/litre, and the need for
      supplemental oxygen or intravenous fluid replacement on admission. CONCLUSIONS:
      There were demographic, ethnic and clinical differences between patients admitted
      with pandemic H1N1 infection and those hospitalised during seasonal influenza
      activity. Despite national policies favouring use of antiviral drugs, few
      patients received these before admission and many were given antibiotics.

PMID- 22407892
TI  - Ablation of both organic cation transporter (OCT)1 and OCT2 alters metformin
      pharmacokinetics but has no effect on tissue drug exposure and pharmacodynamics.
AB  - Organic cation transporter (OCT)1 and OCT2 mediate hepatic uptake and secretory
      renal clearance of metformin, respectively. Pharmacokinetic/pharmacodynamic
      (PK/PD) implications of simultaneous impairment of both transporters, such as by
      systemic pan-OCT inhibition, have not been studied directly. At present metformin
      PK/PD, distribution, and excretion were studied in Oct1/Oct2-knockout mice.
      Metformin clearance was reduced 4.5-fold from renal blood flow to unbound
      glomerular filtration rate, and volume of distribution was reduced 3.5-fold in
      Oct1/Oct2-knockout mice. Oral bioavailability was not affected (F = 64 +/- 4
      versus 59 +/- 11; knockout versus wild type). Liver- and kidney-to-plasma
      concentration ratios were decreased in Oct1/Oct2-knockout mice 4.2- and 2.5-fold,
      respectively. The 2.9-fold increase in oral metformin exposure and reduced tissue
      partitioning yielded little to no net change in tissue drug concentrations.
      Absolute kidney exposure was unchanged (knockout/wild type = 1.1 +/- 0.2), and
      liver exposure was only modestly decreased (knockout/wild type = 0.6 +/- 0.1).
      Oral glucose area under the curve (AUC) lowering by metformin was not impaired in
      Oct1/Oct2-knockout mice at the five dose levels tested (ED50 = 151 versus 110
      mg/kg; glucose lowering at highest dose = 42 +/- 1 versus 39 +/- 4%; knockout
      versus wild type); however, higher systemic metformin exposures were necessary in
      knockout mice to elicit the same effect (half-maximal efficacious AUC = 70 versus
      26 MUg x h/ml). Despite major changes in metformin clearance and volume of
      distribution in Oct1/Oct2-knockout mice, tissue drug exposure and PD were not
      affected. These findings challenge the presumption that systemic OCT inhibition
      will affect metformin pharmacology.

PMID- 22407893
TI  - Complete monosomy 21 confirmed by FISH and array-CGH.

PMID- 22407894
TI  - Ophthalmic changes in severe anorexia nervosa: a case series.
AB  - OBJECTIVE: We describe the diagnosis and management of lagophthalmos, or failure
      of eyelid closure, in five patients with severe anorexia nervosa (AN) who
      complained of dry, irritated eyes and photophobia. METHOD: Five patients with
      these findings are described retrospectively. RESULTS: Examination revealed
      lagopthalmos in the setting of ptosis and enophthalmos, with multiple other
      starvation-mediated medical complications. DISCUSSION: These eye findings, as
      complications of AN, have not been described in the literature. With careful
      protective measures, initiation of nutritional rehabilitation, and intensively
      monitored early refeeding, these patients' ocular abnormalities and associated
      symptoms resolved completely. Recognition of this pathology and appropriate
      management can prevent long-term morbidity in the form of permanent loss of
      visual acuity due to corneal abrasions and improve the outcomes for these
      patients with severe AN.

PMID- 22407895
TI  - Beneficial effect of plasma exchange in the treatment of toxic epidermal
      necrolysis: a series of four cases.
AB  - INTRODUCTION: Toxic epidermal necrolysis (TEN) is a rare, life-threatening
      disease with a high mortality rate that is linked to drug toxicity. There is a
      lack of data about the underlying pathophysiologic mechanisms and treatment
      options. The only widely accepted treatment of TEN is withdrawal of the offending
      drug followed by supportive care. The potential roles of corticosteroids,
      intravenous immunoglobulin (IVIG) and plasmapheresis (TPE) remain controversial.
      AIMS: We present four patients with severe TEN (all with >80% involvement of body
      surface) who were treated with TPE following unsuccessful treatment with
      corticosteroids/IVIG. METHODS: TPE was performed using a COBE Spectra blood cell
      separator. ACD-A was used as anticoagulant fluid and the target-washed plasma
      volume was one body volume. Plasma was replaced by a 5% solution of human albumin
      + Ringer's lactate. RESULTS: The mean number of TPE sessions was 5.25 +/- 2.22
      (range 3-8). Drugs were implicated as an etiologic agent in each case. TPE led to
      prompt improvement of acute condition and general health as well as halting of
      disease progression. Additionally, the restoration of the epithelium began in all
      four patients. CONCLUSION: Plasmapheresis should be considered as an alternative
      treatment modality for patients with the most severe form of TEN if initial
      treatment with other agents, including corticosteroids and/or IVIG, fails. Drugs
      were suspected to be the cause of TEN in all four cases.

PMID- 22407896
TI  - Combined use of filtered and edited 1 H NMR spectroscopy to detect 13 C-enriched
      compounds in complex mixtures.
AB  - In conventional metabolism and pharmacokinetic studies, radioactive isotopes are
      used to identify and quantify the breakdown products of xenobiotics. However, the
      stable isotope (13) C provides a cheaper and less hazardous alternative.
      Metabolites of (13) C-enriched xenobiotics can be detected, quantified and
      identified by (13) C-filtered NMR spectroscopy. However, one obstacle to using
      (13) C is its 1.1% natural abundance that produces a background signal in (13) C
      filtered NMR spectra of crude biological extracts. The signal makes it difficult
      to distinguish between (13) C-enriched xenobiotics resonances from endogenous
      metabolites unrelated to the xenobiotic. This study proposes that the (13) C
      background signal can be distinguished from resonances of (13) C-enriched
      xenobiotics by the absence of a (12) C component in the xenobiotic. This is
      detected by combined analysis of (13) C-filtered and -edited NMR spectra. The
      theory underlying the approach is described and the method is demonstrated by the
      detection of sub-microgram amounts of (13) C-enriched phenacetin in crude
      extracts of hepatocyte microsomes.

PMID- 22407897
TI  - 2D porous honeycomb polymers versus discrete nanocubes from trigonal trinuclear
      complexes and ligands with variable topology.
AB  - Trinuclear building block {Fe(2)NiO(Piv)(6)} (Piv = pivalate), which possessed
      pseudo-D(3h) symmetry, was linked by two ligands, pseudo-D(3h) ligand tris-(4
      pyridyl)pyridine (L1) and C(2v) ligand 4-(N,N-dimethylamino)phenyl-2,6-bis(4
      pyridyl)pyridine (L2) into two products with different topologies: 2D
      coordination polymer [Fe(2)NiO(Piv)(6)(L1)](n) (1), and discrete molecule
      [{Fe(2)NiO(Piv)(6)}(8) {L2}(12)], which had a nanocube structure (2). In compound
      1, trinuclear {Fe(2)NiO(Piv)(6)} blocks were linked through ligand L1 into layers
      with honeycomb topology. In compound 2, eight trinuclear blocks were located in
      the vertices of the nanocube, with each L2 ligand linked to two
      {Fe(2)NiO(Piv)(6)} units. In the crystal structure, these nanocubes formed
      infinite catenated chains. Analysis of possible structures that could be
      assembled from these building blocks showed that compounds 1 and 2 corresponded
      to their respective predicted topologies. Compound [1?solvent] possessed a porous
      structure, in which the voids were filled by solvent molecules (DMF or DMSO).
      This structure was retained following desolvation, and compound 1 absorbed
      significant quantities of N(2) and H(2) at 78 K (S(BET) = 730 m(2)  g(-1), H(2)
      sorption capacity: 0.9 % by weight at 865 Torr). Desolvation of [2?solvent] led
      to disorder of its crystal structure, and compound 2 only adsorbed negligible
      quantities of N(2) but adsorbed 0.27 % H(2) (by weight) at 855 Torr and 78 K. The
      magnetic properties of these complexes (temperature dependence of molar magnetic
      susceptibility) were governed by the magnetic properties of the trinuclear
      "building block".

PMID- 22407898
TI  - Novel pyrazole derivatives as anticancer and radiosensitizing agents.
AB  - The present article describes the synthesis of some novel pyrrole, pyrazolo[4,3
      d]oxazole, pyrrolo[2,3-b]pyridine, 1,2,3-triazole and oxoazetidin derivatives
      incorporating pyrazole moiety, the structures of which were confirmed by
      elemental analyses and spectral data. All the target compounds were subjected to
      in-vitro antitumor activity against liver and colon human tumor cell lines (HEPG2
      and HCT), furthermore, the most potent compounds were evaluated for their ability
      to enhance the cell killing effect of gamma-radiation (radiosensitizing
      evaluation). The results of in-vitro anticancer evaluation showed that compounds
      3 and 16a were the most potent compounds on HEPG2 (IC50=2.6 and 4.2 ug/ml) and
      compounds 2 and 10 were the most potent on HCT (IC50=2.7 and 3.9 ug/ml) compared
      to vinblastine (IC50=4.6 on HEPG2 and 2.6 ug/ml on HCT), while, the activity of
      the most potent compounds increased after combination with gamma-radiation and
      they showed no toxicity on normal hepatocytes and colon cells at their effective
      concentrations.

PMID- 22407899
TI  - Antimicrobial therapy and outcome of septicemia patients admitted to a University
      Hospital in Delhi.
AB  - Septicemia is a common clinical condition encountered in most of the hospitals in
      this region of the world. However, limited information is available in the Indian
      literature on antimicrobial usage in patients with suspected or proven cases of
      septicemia. The aim of the present study is on the one hand to describe the
      clinical characteristics of septicemia, the causative pathogens, the current
      pattern of antimicrobial use, the clinical outcome, the acquisition cost of
      commonly used antimicrobial regimens and on the other hand to monitor adverse
      drug reactions (ADRs) during therapy of septicemia patients admitted to a
      University Hospital in Delhi. We prospectively reviewed the antimicrobial therapy
      in 34 clinically diagnosed septicemia cases admitted to a University Hospital
      from July 2009 to December 2009. All study patients presented various clinical
      signs and symptoms, fever, diarrhoea and vomiting were most commonly reported.
      Microorganisms could be identified in 13 (38.2%) of the patients. Escherichia
      coli (41.2%) constituted the most prevalent bacterial pathogen. Among culture
      positive patients, 15.4% received ceftriaxone as the most common empirical
      antimicrobial therapy; among culture negative patients, 19% received cefotaxime
      plus amikacin as the most common empirical antimicrobial therapy. The average
      acquisition cost of the 1st line antimicrobial regimen was higher in culture
      positive than in culture negative patients, but it was reversed for the 2nd line
      therapy. Overall, 67.6% patients were discharged after recovery, 23.5% were
      transferred out and 8.8% died during the course of therapy. 9 (26.5%) patients
      experienced ADRs during the antimicrobial therapy. These findings may have an
      important implication for developing comprehensive, evidence-based guidelines for
      the practical treatment of septicemia, adherence to which may lead to a more
      rational antimicrobial therapy, to cost reduction and to an improved level of
      care of patients with septicemia.

PMID- 22407900
TI  - Relative bioavailability of two 5-mg montelukast sodium chewable tablets: a
      single dose, randomized, open-label, 2-period crossover comparison in healthy
      korean adult male volunteers.
AB  - Montelukast sodium, cysteinyl leukotriene receptor 1 specific antagonist, has
      been marketed in Korea for the treatment of bronchial asthma and allergic
      rhinitis. The aim of this study was to compare the pharmacokinetics and relative
      bioavailability of a test and reference formulation of montelukast 5-mg chewable
      tablets in healthy Korean male volunteers to meet KFDA regulatory criteria for
      marketing of the new generic formulation. This study was designed as a single
      dose, 2-treatment, and 2-period crossover trial with 32 healthy volunteers. Each
      subject was randomly assigned to receive the test (Dong-Kook Montelukast Sodium
      Chewable Tablet 5 mg(r)) or reference (Singulair Chewable Tablet 5 mg(r))
      formulation. The tablet was chewed 20 times, and then swallowed with 240 mL of
      water. Plasma concentrations of montelukast up to 24 h after the dose were
      determined using a validated UPLC-MS/MS method, and the bioequivalence between
      the 2 formulations was assessed by statistical analysis of mean ratios of log
      transformed AUC0-24 h and Cmax. No period or sequence effects were detected. The
      AUC0-24 h was 1 835 ng.h/mL for the test formulation, and 1 930 ng.h/mL for the
      reference formulation. The respective values of AUC0-infinity were 1 917 and 2
      015 ng.h/mL. The Cmax of the test and reference products (247 and 283 ng/mL,
      respectively) reached at 2.25 and 2.72 h, respectively. Then, they gradually
      decreased with the mean terminal t1/2 of 5.25 and 5.30 h for the test and
      reference products, respectively. The 90% CIs for the ratio of log-transformed
      AUC0-24 h and Cmax for the test and reference formulations were 0.92-0.99 and
      0.83-0.91, respectively. No adverse events were reported in this study. This
      single dose study found that the test and reference products met the regulatory
      criteria for bioequivalence in these fasting healthy Korean male volunteers.

PMID- 22407901
TI  - Lewis acid catalyzed intramolecular [4+2] and [3+2] cross-cycloaddition of
      alkynylcyclopropane ketones with carbonyl compounds and imines.

PMID- 22407902
TI  - Real-time observation on dynamic growth/dissolution of conductive filaments in
      oxide-electrolyte-based ReRAM.
AB  - Evolution of growth/dissolution conductive filaments (CFs) in oxide-electrolyte
      based resistive switching memories are studied by in situ transmission electron
      microscopy. Contrary to what is commonly believed, CFs are found to start growing
      from the anode (Ag or Cu) rather than having to reach the cathode (Pt) and grow
      backwards. A new mechanism based on local redox reactions inside the oxide
      electrolyte is proposed.

PMID- 22407903
TI  - Th2 cytokine-mediated methimazole-induced acute liver injury in mice.
AB  - Drug-induced liver injury (DILI) is a major safety concern in drug development
      and clinical practice. The pathogenesis of DILI usually involves the
      participation of the parent drug or metabolites that either affect cellular
      function or elicit an immune response. However, the mechanisms leading to DILI
      are unknown in most cases. Methimazole (MTZ) is used as an antithyroid drug and
      is well known to have induced liver injuries such as cholestatic hepatitis in a
      small number of human cases. Immune-mediated reactions were also suggested to
      play a role in MTZ-induced acute liver injury, but the mechanism underlying this
      process has not been elucidated. To address this issue, we measured plasma
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels,
      hepatic glutathione levels, hepatic expression of CD4+ Th cell-related
      transcriptional factors, cytokines and chemokines, plasma interleukin (IL)-4
      levels and histopathological changes in the liver following MTZ (450 mg kg-1 ,
      p.o.) administration in mice. The hepatic expression of mRNA for Th2 cell-related
      factors, such as GATA-binding protein, macrophage inflammatory protein-2 (MIP-2)
      and plasma IL-4 levels, as well as plasma AST and ALT levels, was significantly
      increased in mice treated with MTZ. These changes were markedly enhanced by pre
      treatment with L-buthionine sulfoximine (3 mmol kg-1, i.p.) and MTZ (15 mg kg-1,
      p.o.). Neutralization of IL-4 using a monoclonal anti-mouse IL-4 antibody (100
      ug/mouse, single i.p.) suppressed the hepatotoxic effect of MTZ. In conclusion,
      this report is the first to demonstrate that Th2 cytokine-mediated immune
      responses are involved in MTZ-induced acute liver injury in mice.

PMID- 22407904
TI  - Development of inflammatory bowel disease in patients with solid organ
      transplant.

PMID- 22407905
TI  - Assessment of training effects on autonomic modulation of the cardiovascular
      system in mature rats using power spectral analysis of heart rate variability.
AB  - OBJECTIVE: To clarify the effects of forced or voluntary exercise on autonomic
      modulation of the cardiovascular system, we monitored changes in autonomic
      nervous activity in a mature rat by spectral analysis of the heart rate (HR)
      during a 10-week training period. METHODS: Male Wistar rats implanted with a
      radio-telemetry system were divided into three groups at 18 weeks of age: (1)
      Control group (n = 8); (2) Voluntary group (n = 6), which were housed separately
      in a cage with a running wheel; (3) Forced group (n = 6), which were exercised on
      a treadmill (35 m/min, 15 min/day, 5 days/week). The electrocardiogram was
      analyzed by the maximum entropy method into two main oscillations, low-frequency
      (LF) and high-frequency (HF) oscillations, respectively. LF and HF are considered
      to be markers of both sympathetic and parasympathetic modulations and
      parasympathetic modulation, respectively. RESULTS: Average running distances of
      the Voluntary group were more than twofold higher than those of the Forced group.
      HR levels in the Forced group were lower than those in the Control group. LF and
      HF levels in the Control and the Forced groups were almost the same during the
      experiment, and those in the Voluntary group showed a tendency to decrease.
      CONCLUSION: The results in the Voluntary and the Forced groups suggest that
      cardiovascular adjustments are not simply caused by the quantity of exercise. In
      the Voluntary group, both sympathetic and parasympathetic activity may decrease
      with a predominance of sympathetic activity. Conversely, in the Forced group, the
      baroreflex may be hyper-activated by the undesired treadmill running and handling
      stress.

PMID- 22407907
TI  - Predictors of complications of free flap reconstruction in head and neck surgery:
      Analysis of 304 free flap reconstruction procedures.
AB  - OBJECTIVES: The objectives of this study were to classify and analyze
      perioperative complications following free flap reconstruction in the head and
      neck and investigate potential predictors of these complications. METHODS: A
      retrospective chart analysis of 304 consecutive free flap reconstructions for
      defects in the head and neck were examined. Patient and operative characteristics
      as well as complications were recorded prospectively and analyzed using ordinal
      logistic regression. RESULTS: The overall complication rate was 32.6% with a
      perioperative mortality rate of 0.3%. The flap loss rate was 2.0% and the partial
      flap necrosis rate was 1.0%. Multivariate analysis demonstrated a significant
      correlation between perioperative complication and tumor stage as well as
      reconstruction site. CONCLUSIONS: The rate and grade of complications with free
      flap reconstruction in the head and neck were found to be low. Higher tumor stage
      and pharyngoesophageal reconstruction were found to be associated with increased
      complication grades, whereas preoperative radiation alone and chemoradiation were
      not. Smoking and alcohol use, age, diabetes mellitus, peripheral vascular
      disease, and preoperative myocardial infarction as well as preoperative
      cerebrovascular accident were not found to be associated with increased
      complications. No statistically significant difference in complication grades was
      found with different flap types or indications for reconstruction.

PMID- 22407906
TI  - Simultaneous changes in high-fat and high-cholesterol diet-induced
      steatohepatitis and severe fibrosis and  those underlying molecular mechanisms in
      novel SHRSP5/Dmcr rat.
AB  - OBJECTIVES: The aim of this study was to identify the molecular mechanisms
      underlying high-fat and high-cholesterol (HFC) diet-induced steatohepatitis and
      associated liver fibrosis progression in a novel stroke-prone, spontaneously
      hypertensive 5/Dmcr (SHRSP5/Dmcr) rat model. METHODS: SHRSP5/Dmcr rats were given
      the control or HFC-diet for 2, 8, and 16 weeks. Plasma and hepatic gene
      expression of key molecules involved in fatty acid oxidation, inflammation,
      oxidative stress, and fibrosis were subsequently analyzed. RESULTS: Rats fed the
      HFC-diet showed increased plasma tumor necrosis factor-alpha (TNF-alpha) and
      hepatic p50/p65 signals, but reduced hepatic Cu(2+)/Zn(2+)-superoxide dismutase
      across the treatment period and reduced plasma total adiponectin at 8 weeks. In
      HFC-diet-fed rats, transforming growth factor-beta1 (TGF-beta1) was elevated
      prior to the appearance of obvious liver fibrosis pathology at 2 weeks, followed
      by elevations in platelet-derived growth factor-B (PDGF-B) and alpha-smooth
      muscle actin (alpha-SMA), corresponding to evident liver fibrosis, at 8 weeks and
      by alpha(1) type I collagen production at 16 weeks. The HFC-diet increased
      hepatic total cholesterol accumulation, although hepatic triglyceride declined by
      0.3-fold from 2 to 16 weeks due to reduced hepatic triglyceride synthesis, as
      suggested by the diacylglycerol acyltransferase 1 and 2 measurements.
      CONCLUSIONS: TNF-alpha and p50/p65 molecular signals appeared to be major factors
      for HFC-diet-induced hepatic inflammation and oxidative stress facilitating liver
      disease progression. While the up-regulation of TGF-beta1 prior to the appearance
      of any evident liver fibrosis could be an early signal for progressive liver
      fibrosis, elevated PDGF-B and alpha-SMA levels signified evident liver fibrosis
      at 8 weeks, and subsequent increased alpha(1) type I collagen production and
      reduced triglyceride synthesis indicated extensive liver fibrosis at 16 weeks in
      this novel SHRSP5/Dmcr model.

PMID- 22407908
TI  - Thermal ammonia activation by cationic transition-metal hydrides of the first row
      -small but mighty.
AB  - The thermal reactions of cationic 3d transition-metal hydrides MH(+) (M=Sc-Zn,
      except V and Cu) with ammonia have been studied by gas-phase experiments and
      computational methods. There are three primary reaction channels: 1) H(2)
      elimination by N-H bond activation, 2) ligand exchange under the formation of
      M(NH(3))(+), and 3) proton transfer to yield NH(4)(+). Computational studies of
      these three reaction channels have been performed for the couples MH(+)/NH(3)
      (M=Sc-Zn) to elucidate mechanistic aspects and characteristic reaction patterns
      of the first row. For N-H activation, sigma-bond metathesis was found to be
      operative.

PMID- 22407909
TI  - Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic
      resonance imaging predicts the histological grade of hepatocellular carcinoma
      only in patients with Child-Pugh class A cirrhosis.
AB  - The aim of this study was to investigate the role of gadolinium ethoxybenzyl
      diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance
      imaging (MRI) in predicting the histological grade of hepatocellular carcinoma
      (HCC) according to the hepatic function. Eighty-one consecutive patients with 122
      histologically proven HCCs who underwent Gd-EOB-DTPA-enhanced MRI before
      resection (45 HCCs in 42 patients) or transplantation (77 HCCs in 39 patients)
      were analyzed retrospectively. We calculated the relative enhancement ratios
      (RER), which is the ratio of the relative intensity of a tumor versus the
      surrounding parenchyma on hepatobiliary phase images to the relative intensity on
      unenhanced MRI scans. We then analyzed the correlation between the RER and the
      tumor differentiation grade in patients with various degrees of hepatic function.
      The degree of tumor enhancement, which included the precontrast relative
      intensity ratio (RIR), the postcontrast RIR, and the RER, for well-differentiated
      (WD) HCCs was significantly higher than the degree of tumor enhancement for
      moderately differentiated and poorly differentiated (PD) HCCs (P = 0.001 and P =
      0.001, respectively, for precontrast RIRs; P < 0.001 and P < 0.001, respectively,
      for postcontrast RIRs; and P = 0.01 and P = 0.001, respectively, for RERs). In a
      subgroup analysis based on liver function, the correlation between the
      histological grade and the enhancement ratio was demonstrated only in the group
      of patients with Child-Pugh class A cirrhosis. The accuracy of postcontrast RIRs
      for predicting WD and PD HCCs was favorable; the areas under the receiver
      operating characteristic curves were 0.896 [95% confidence interval (CI) = 0.817
      0.974] and 0.769 (95% CI = 0.658-0.879), respectively. In conclusion, the
      hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI may help to predict the
      differentiation of HCCs, especially in HCC patients with Child-Pugh class A
      cirrhosis before liver transplantation or resection.

PMID- 22407910
TI  - Bone geometry, density, and microarchitecture in the distal radius and tibia in
      adults with osteogenesis imperfecta type I assessed by high-resolution pQCT.
AB  - Osteogenesis imperfecta (OI) is a hereditary disorder characterized by decreased
      biosynthesis or impaired morphology of type I collagen that leads to decreased
      bone mass and increased bone fragility. We hypothesized that patients with OI
      have altered bone microstructure and bone geometry. In this cross-sectional study
      we compared patients with type I OI to age- and gender-matched healthy controls.
      A total of 39 (13 men and 26 women) patients with OI, aged 53 (range, 21-77)
      years, and 39 controls, aged 53 (range, 21-77) years, were included in the study.
      Twenty-seven of the patients had been treated with bisphosphonates. High
      resolution peripheral quantitative computed tomography (HR-pQCT) at the distal
      radius and distal tibia and dual-energy X-ray absorptiometry of total hip,
      femoral neck, trochanteric region, and the lumbar spine (L1-L4) were performed.
      The patients were shorter than the controls (159 +/- 10 cm versus 170 +/- 9 cm, p
      < 0.001), but had similar body weight. In OI, areal bone mineral density (aBMD)
      was 8% lower at the hip (p < 0.05) and 13% lower at the spine (p < 0.001)
      compared with controls. The trabecular volumetric bone mineral density (vBMD) was
      28% lower in radius (p < 0.001) and 38% lower in tibia (p < 0.001) in OI compared
      with controls. At radius, total bone area was 5% lower in OI than in controls (p
      < 0.05). In the tibia, cortical bone area was 18% lower in OI (p < 0.001). In
      both radius and tibia the number of trabeculae was lower in patients compared to
      the controls (35% and 38%, respectively, p < 0.001 at both sites). Furthermore,
      trabecular spacing was 55% higher in OI in both tibia and radius (p < 0.001 at
      both sites) when compared with controls. We conclude that patients with type I OI
      have lower aBMD, vBMD, bone area, and trabecular number when compared with
      healthy age- and gender-matched controls.

PMID- 22407911
TI  - Frizzled receptors in neurons: from growth cones to the synapse.
AB  - The Wnt signaling pathway has been implicated in several different aspects of
      neural development and function, including dendrite morphogenesis, axonal growth
      and guidance, synaptogenesis and synaptic plasticity. Here, we studied several
      Frizzled Wnt receptors and determined their differential expression during
      hippocampal development. In cultured hippocampal neurons, the cellular
      distributions of Frizzleds vary greatly, some of them being localized at
      neurites, growth cones or synaptic sites. These findings suggest that the Wnt
      signaling pathway might be temporally and spatially fine tuned during the
      development of neuronal circuits through specific Frizzled receptors.

PMID- 22407912
TI  - Eating disorder not otherwise specified presentation in the US population.
AB  - OBJECTIVE: To examine prevalence and clinical correlates of eating disorder not
      otherwise specified (EDNOS) in the US population. METHOD: Two cross-sectional
      surveys of adults and adolescents used the WHO CIDI to assess DSM-IV criteria for
      anorexia nervosa (AN), bulimia nervosa (BN), and EDNOS. RESULTS: Lifetime
      prevalence of EDNOS was 4.78% in adolescents and 4.64% in adults. The majority of
      adolescents and adults with an eating disorder presented with EDNOS. Three
      quarters of participants with EDNOS met criteria for comorbid disorders, while
      one-quarter endorsed suicidality. Severity correlates were equally prevalent in
      EDNOS and AN, whereas comparisons between EDNOS and BN varied by specific
      correlate and sample. Adolescents with subthreshold AN (SAN) endorsed more
      anxiety than AN (p < .05), and adolescents and adults with SAN endorsed more
      suicidal plans than AN (p's < .05). DISCUSSION: Findings increase our
      understanding of the clinical relevance of EDNOS. Eating disorder diagnostic
      nomenclature requires modification to capture the full spectrum. (c) 2012 by
      Wiley Periodicals, Inc. Int J Eat Disord 2012.

PMID- 22407913
TI  - HLA-DQA2 and HLA-DQB2 genes are specifically expressed in human Langerhans cells
      and encode a new HLA class II molecule.
AB  - The precise role of human epidermal Langerhans cells (LCs) in immune response is
      highly controversial. While studying the gene expression profile of these cells,
      we were intrigued to identify the HLA-DQB2 gene as potentially expressed in LCs.
      Despite a strong evolutionary conservation of their sequences, the concomitant
      expression of the poorly polymorphic HLA-DQA2/HLA-DQB2 genes, paralogous to the
      HLA-DQA1/HLA-DQB1 genes, has never been detected in any cell type. We confirmed
      by RT-PCR that the HLA-DQA2 and -DQB2 genes are both expressed in LCs, but not in
      monocyte-derived dendritic cells, or in blood CD1c(+) or plasmacytoid dendritic
      cells. The presence of the HLA-DQbeta2 chain in LCs could be demonstrated by
      Western blotting, whereas immunofluorescence revealed its localization in early
      endosomes. As in the case of other HLA class II molecules, the HLA-DQalpha2 and 
      DQbeta2 chains formed heterodimers that had to associate with the invariant chain
      to reach endosomal compartments. HLA-DQalpha2/beta2 heterodimers were expressed
      at the cell surface, where they could mediate staphylococcal superantigen
      stimulation of T cells. Interestingly, HLA-DQalpha2 and HLA-DQbeta1 chains formed
      mixed heterodimers which efficiently left the endoplasmic reticulum. These
      observations strongly suggest that the poorly polymorphic HLA-DQA2 and -DQB2
      genes should be considered to be of immunological importance. The HLA
      DQalpha2/beta2 molecules could influence the complexity of the repertoire of Ags
      presented by LCs.

PMID- 22407914
TI  - gamma-Herpesvirus reactivation differentially stimulates epitope-specific CD8 T
      cell responses.
AB  - The gamma-herpesviruses are characterized by their ability to establish lifelong
      latency. Subsequent immune suppression leads to viral reactivation from latency
      and the onset of a variety of pathologies, including lymphoproliferative disease
      and cancers. CD8 T cells play a key role in preventing reactivation of latent
      virus. Therefore, to develop effective therapeutic immune strategies, it is
      essential to understand the maintenance of CD8 T cell responses during latency.
      Because the gamma-herpesviruses are highly species-specific and mice cannot be
      infected with the human pathogens, EBV or Kaposi's sarcoma-associated
      herpesvirus, we have used a natural rodent gamma-herpesvirus experimental
      infection model, gamma-herpesvirus-68. In this report, we show that during long
      term latent infection, naive CD8 T cells are recruited into the ongoing immune
      response in an epitope-specific manner. When virus reactivation is induced in
      vivo, the recruitment of CD8 T cells for some, but not all, epitopes is enhanced.
      The variation in recruitment is not due to differences in epitope presentation.
      We also show that CD8 T cells that are newly stimulated during reactivation are
      functionally impaired compared with acutely stimulated cells in terms of cytokine
      production. Thus, our results demonstrate unexpected complexity in the response
      of CD8 T cells specific for different viral epitopes that were stimulated during
      acute infection, quiescent latency, and reactivation.

PMID- 22407915
TI  - A deficiency in nucleoside salvage impairs murine lymphocyte development,
      homeostasis, and survival.
AB  - The homeostasis of the immune system is tightly controlled by both cell-extrinsic
      and -intrinsic mechanisms. These regulators, not all known to date, drive cells
      in and out of quiescence when and where required to allow the immune system to
      function. In this article, we describe a deficiency in deoxycytidine kinase
      (DCK), one of the major enzymes of the nucleoside salvage pathway, which affects
      peripheral T cell homeostatic proliferation and survival. As a result of an N
      ethyl-N-nitrosourea-induced mutation in the last alpha helix of DCK, a
      functionally null protein has been generated in the mouse and affects the
      composition of the hematopoietic system. Both B and T lymphocyte development is
      impaired, leading to a state of chronic lymphopenia and to a significant increase
      in the number of myeloid cells and erythrocytes. In the periphery, we found that
      mutant lymphocytes adopt a CD44(high)CD62L(low) memory phenotype, with high
      levels of proliferation and apoptosis. These phenotypes are notably the result of
      a cell-extrinsic-driven lymphopenia-induced proliferation as wild-type cells
      transferred into DCK-deficient recipients adopt the same profile. In addition,
      DCK also regulates lymphocyte quiescence in a cell-intrinsic manner. These data
      establish dCK as a new regulator of hematopoietic integrity and lymphocyte
      quiescence and survival.

PMID- 22407917
TI  - Regulatory T cells selectively preserve immune privilege of self-antigens during
      viral central nervous system infection.
AB  - Regulatory T cells (Tregs) are important for the attenuation of immune reactions.
      During viral CNS infections, however, an indiscriminate maintenance of CNS immune
      privilege through Treg-mediated negative regulation could prevent autoimmune
      sequelae but impair the control of viral replication. We analyzed in this study
      the impact of Tregs on the development of acute viral encephalomyelitis, T cell
      mediated antiviral protection, and prevention of CNS autoimmunity following
      intranasal infection with the gliatropic mouse hepatitis virus strain A59. To
      assess the contribution of Tregs in vivo, we specifically depleted CD4(+)Foxp3(+)
      T cells in a diphtheria toxin-dependent manner. We found that depletion of Tregs
      had no impact on viral distribution and clearance and did not significantly alter
      virus-specific CD4(+) and CD8(+) T cell responses. However, Treg depletion led to
      a more severe CNS inflammation associated with neuronal damage. Dissection of the
      underlying immunopathological mechanisms revealed the elaborate Treg-dependent
      regulation of self-reactive CD4(+) T cell proliferation within the CNS-draining
      lymph node and downtuning of CXCR3 expression on T cells. Taken together, these
      results suggest that Tregs preserve CNS immune privilege through selective
      control of CNS-specific Th cells while keeping protective antiviral immunity
      fully operative.

PMID- 22407916
TI  - A second TCRdelta locus in Galliformes uses antibody-like V domains: insight into
      the evolution of TCRdelta and TCRMU genes in tetrapods.
AB  - Analyses of the available avian genomes revealed the presence of a second
      TCRdelta locus in the Galliformes. This second TCRdelta locus is nonsyntenic to
      the conventional TCRalpha/delta and is unusual in that the V genes are more
      related to IgH V genes (VH) than to TCR V genes. The second TCRdelta is not found
      in another avian lineage, the passerine zebra finch. Rather the finch's
      conventional TCRalpha/delta locus contains VH genes that are expressed with the
      conventional Cdelta gene, similar to what has been found in amphibians. A
      comparison between Galliformes and Passeriformes genomic organization suggests an
      origin of the second TCRdelta in the former lineage involving gene duplication.
      Expression of these atypical TCRdelta transcripts with a VH domain paired with
      Cdelta was found in lymphoid tissues of both avian lineages. The configuration of
      the second TCRdelta in chicken and turkey is reminiscent of the TCRdelta
      duplication that is present in nonplacental mammals and provides insight into the
      origin of the uniquely mammalian TCRMU locus.

PMID- 22407918
TI  - Enhancing immunostimulatory function of human embryonic stem cell-derived
      dendritic cells by CD1d overexpression.
AB  - Human embryonic stem cell-derived dendritic cells (hESC-DCs) may potentially
      provide a platform to generate "off-the-shelf" therapeutic cancer vaccines. To
      apply hESC-DCs for cancer immunotherapy in a semiallogeneic setting, it is
      crucial for these cells to "jump-start" adaptive antitumor immunity before their
      elimination by host alloreaction. In this study, we investigated whether CD1d
      upregulation in hESC-DCs may exploit invariant NKT (iNKT) cell adjuvant activity
      and boost antitumor immunity. Using a baculoviral vector carrying the CD1d gene,
      we produced CD1d-overexpressing hESC-DCs and demonstrated that the upregulated
      CD1d was functional in presenting alpha-galactosylceramide for iNKT cell
      expansion. Pulsed with melanoma Ag recognized by T cell 1 peptide, the CD1d
      overexpressing hESC-DCs displayed enhanced capability to prime CD8(+) T cells
      without relying on alpha-galactosylceramide loading. Blocking the CD1d with Ab
      reduced the immunogenicity, suggesting the importance of hESC-DC and iNKT cell
      interaction in this context. The CD1d-overexpressing hESC-DCs also induced a
      proinflammatory cytokine profile that may favor the T cell priming. Moreover, a
      similar immunostimulatory effect was observed when the CD1d upregulation strategy
      was applied in human monocyte-derived dendritic cells. Therefore, our study
      suggests that the upregulation of CD1d in hESC-DCs provides a novel strategy to
      enhance their immunogenicity. This approach holds potential for advancing the
      application of hESC-DCs into human cancer immunotherapy.

PMID- 22407919
TI  - Canonical type I IFN signaling in simian immunodeficiency virus-infected
      macrophages is disrupted by astrocyte-secreted CCL2.
AB  - HIV-associated neurologic disorders are a mounting problem despite the advent of
      highly active antiretroviral therapy. To address mechanisms of HIV-associated
      neurologic disorders, we used an SIV pigtailed macaque model to study innate
      immune responses in brain that suppress viral replication during acute infection.
      We previously reported that during acute infection in brain, noncanonical type I
      IFN signaling occurs, where IFN-beta mRNA is induced while IFN-alpha is
      simultaneously suppressed. Two downstream IFN-stimulated genes, MxA and TRAIL,
      also show differential expression patterns. In this study, we show that
      differential signaling is due to interactions between macrophages and astrocytes.
      Astrocytes produce high levels of CCL2 upon SIV infection, which binds to CCR2
      receptors on macrophages, leading to a selective suppression of IFN-alpha and the
      IFN-stimulated gene TRAIL while simultaneously inducing IFN-beta and MxA. The
      interactions between chemokine and cytokine pathways are a novel finding that may
      specifically occur in the CNS.

PMID- 22407920
TI  - Coordination between TLR9 signaling in macrophages and CD3 signaling in T cells
      induces robust expression of IL-30.
AB  - IL-30, the p28 subunit of IL-27, interacts with EBV-induced gene 3 to form IL-27,
      which modulates both proinflammatory and anti-inflammatory responses during
      autoimmune or infectious disease. It also acts as a natural antagonist of gp130,
      thereby attenuating the signals of other gp130-associated cytokines. IL-30
      regulation via LPS has been reported by others, but the intercellular
      communication that induces IL-30 expression is unknown. In this study, we show
      that treatment with anti-CD3/CD28 Abs plus CpG oligodeoxynucleotides induces
      robust expression of IL-30, whereas either treatment alone induces only low
      expression of IL-30. This observation in vitro mirrors the murine model in which
      administration of CpG under inflammatory conditions in vivo induces IL-30
      expression. This robust induction of IL-30 occurs through the coordination of
      helper CD4(+) T cells and innate immune cells (e.g., macrophages) and, to a
      lesser degree, B cells via the CD40/CD154 signaling pathway. These findings
      reveal a previously unrecognized mechanism that integrates signaling pathways
      from T cells and macrophages at the cellular level to induce IL-30 expression.

PMID- 22407921
TI  - HIV-1 proteins preferentially activate anti-inflammatory M2-type macrophages.
AB  - HIV-1 proteins, including Tat, gp120, and Nef, activate macrophages (MPhi), which
      is consistent with the fact that HIV-1 infection is characterized by sustained
      immune activation. Meanwhile, MPhi are functionally classified into two types:
      proinflammatory M1-MPhi and anti-inflammatory M2-MPhi. We show that HIV-1
      proteins, particularly Nef, preferentially activate M2-MPhi. Extracellular Tat,
      gp120, and Nef activated MAPK and NF-kappaB pathways in human peripheral blood
      monocyte-derived MPhi. However, the activation was marked in M-CSF-derived M2
      MPhi but not GM-CSF-derived M1-MPhi. Nef was the most potent activator, and its
      signaling activation was comparable to that by TNF-alpha. Indeed, Nef was
      internalized more rapidly by M2-MPhi than by M1-MPhi. The myristoylation and
      proline-rich motif of Nef were responsible for the observed signaling activation.
      Consistent with the activation of MAPK/NF-kappaB pathways, Nef stimulated the
      production of a number of proinflammatory cytokines/chemokines by M2-MPhi.
      However, Nef reduced the expression of CD163 and phagocytosis, the characteristic
      markers of M2-MPhi, indicating that Nef drives an M2-like to M1-like phenotypic
      shift. Because the differentiation of most tissue MPhi depends on M-CSF and its
      receptor, which is the essential axis for the anti-inflammatory M2-MPhi
      phenotype, the current study reveals an efficient mechanism by which HIV-1
      proteins, such as Nef, induce the proinflammatory MPhi.

PMID- 22407922
TI  - Expression of natural autoantibodies in MRL-lpr mice protects from lupus
      nephritis and improves survival.
AB  - Natural autoantibodies (NAA) and their associated B cells constitute a
      substantial proportion of the normal Ab and B cell repertoire. They often have
      weak reactivity toward a variety of self-Ags such as DNA, nucleoproteins, and
      phospholipids. It remains controversial whether NAA contribute to or protect from
      autoimmune diseases. Using site-directed transgenic (sd-tg) mice expressing a
      prototypic NAA, we investigated the effect of NAA and NAA-producing B cells in
      disease development in the autoimmune-prone MRL/MpJ-Fas(lpr) (MRL-lpr) mice. We
      found that the expression of NAA in MRL-lpr mice prevented proteinuria and
      reduced kidney immune complex formation. The mice had significantly improved
      survival. Administration of the IgM NAA to MRL-lpr mice also delayed the onset of
      nephritis. The sd-tg MRL-lpr mice had decreased levels of anti-dsDNA Abs, anti
      Hep2 nuclear Abs, and anti-Sm/ribonucleoprotein Abs. There is a shift in the IgG
      subclass profile from IgG2a and IgG3 to IgG1 in the sd-tg MRL-lpr mice. The
      CD4(+) T cells from the sd-tg MRL-lpr mice had increased expression of the
      negative costimulatory molecule CTLA-4 and increased production of IL-10 as
      compared with those from the wild-type mice. Furthermore, the NAA B cells
      produced large amounts of IL-10 upon TLR stimulation. These results indicate that
      NAA and NAA-producing B cells play an important role in protection from lupus
      nephritis and suggest that the NAA B cells may have an immune regulatory function
      via the provision of IL-10.

PMID- 22407923
TI  - Phase-adjusted echo time (PATE)-averaging 1 H MRS: application for improved
      glutamine quantification at 2.89 T.
AB  - (1) H MRS investigations have reported altered glutamatergic neurotransmission in
      a variety of psychiatric disorders. The unraveling of glutamate from glutamine
      resonances is crucial for the interpretation of these observations, although this
      remains a challenge at clinical static magnetic field strengths. Glutamate
      resolution can be improved through an approach known as echo time (TE) averaging,
      which involves the acquisition and subsequent averaging of multiple TE steps. The
      process of TE averaging retains the central component of the glutamate methylene
      multiplet at 2.35 ppm, with the simultaneous attenuation of overlapping phase
      modulated coupled resonances of glutamine and N-acetylaspartate. We have
      developed a novel post-processing approach, termed phase-adjusted echo time
      (PATE) averaging, for the retrieval of glutamine signals from a TE-averaged (1) H
      MRS dataset. The method works by the application of an optimal TE-specific phase
      term, which is derived from spectral simulation, prior to averaging over TE
      space. The simulation procedures and preliminary in vivo spectra acquired from
      the human frontal lobe at 2.89 T are presented. Three metabolite normalization
      schemes were developed to evaluate the frontal lobe test-retest reliability for
      glutamine measurement in six subjects, and the resulting values were comparable
      with previous reports for within-subject (9-14%) and inter-subject (14-20%)
      measures. Using the acquisition parameters and TE range described, glutamine
      quantification is possible in approximately 10 min. The post-processing methods
      described can also be applied retrospectively to extract glutamine and glutamate
      levels from previously acquired TE-averaged (1) H MRS datasets.

PMID- 22407924
TI  - Novel brain targeting prodrugs of naproxen based on dimethylamino group with
      various linkages.
AB  - As a preventive and treatment drug for Alzheimer's disease (AD), naproxen's
      clinical application is hampered by its limited distribution in the brain. To
      increase the delivery of naproxen across the blood-brain barrier (BBB), 3
      prodrugs (P1, P2 and P3) of naproxen were synthesized through either ester bond
      or amido bond using the dimethylamino moiety as a brain-targeting ligand. The in
      vitro release of naproxen from the 3 prodrugs was studied in PBS, rat plasma and
      brain homogenate. P3 with an amido bond appeared to be highly stable in all
      incubation media, whereas P1 and P2 with ester bonds were partially hydrolyzed in
      alkaline environment and brain homogenate to yield the parent drug. After i. v.
      administration to rats, the brain concentration of total naproxen (summation of
      released and bound naproxen, TN) of P1, P2 and P3 groups were 28.81, 24.51 and
      15.54 times greater than that of the control naproxen group at 5 min,
      respectively, and the brain AUC0-t were 6.94, 10.06 and 6.70 times greater than
      that of the control naproxen group. In addition, the Cmax of TN in the brain
      after the administration of prodrugs with ester bonds (P1 and P2) was higher than
      that of the amide prodrug (P3). The results highlighted the possibility of brain
      delivery of naproxen using prodrug strategies based on the brain-targeting ligand
      with dimethylamino moiety, in which the linkage between drug and targeting group
      might play an important role in modulating the in vivo behaviors of these
      prodrugs.

PMID- 22407925
TI  - Calcium transport genes are differently regulated in maternal and fetal placenta
      in the knockout mice of calbindin-D(9k) and -D(28k).
AB  - Calbindin-D(9k) (CaBP-9k) and -D(28k) (CaBP-28k) are cytosolic proteins with EF
      hand motifs that have a high affinity for calcium ions. Many types of calcium
      channels and intracellular calcium binding proteins, such as sodium/calcium
      exchangers (NCXs) and transient receptor potential cation channels (TRPVs), have
      been detected in the placenta. In this study, the expression of calcium channels
      involved in maternal-fetal calcium transport were investigated in wild-type mice
      versus CaBP-9k, CaBP-28k, and CaBP-9k/28k double knockout (KO) mouse models. The
      expression of calcium transport genes in three dissected sections of the placenta
      (maternal, central, and fetal) was examined on gestational day 19 (GD 19). The
      expression of CaBP-9k, TRPV6, TRPV5, and NCX1 mRNA was high in fetal compared to
      maternal placenta, while CaBP-28k was abundant in the maternal placenta. CaBP-9k
      was enhanced in all sections of placenta in CaBP-28k KO mice, whereas CaBP-28k
      was reduced in CaBP-9k KO mice. The expression of TRPV6, TRPV5, and NCX1 were
      induced in both maternal and fetal placentas in CaBP-9k KO mice, but were
      upregulated in maternal and central placentas of CaBP-28k KO mice. The levels of
      these proteins showed similar patterns with those of their mRNA. Placental CaBP
      9k, TRPV6, TRPV5, and NCX1 proteins were abundantly expressed in the
      intraplacental yolk sac located in the fetal placenta. CaBP-28k did not
      colocalize with other calcium transport genes, although it was enriched in the
      placental trophoblasts of the decidual zone in the maternal placenta. These
      results indicate that placental TRPV6, TRPV5, and NCX1 compensate for CaBPs in
      CaBP-9k and/or CaBP-28k KO mice, and may take over the roles of CaBP-9k and CaBP
      28k to transfer calcium ions in the placenta. Taken together, these results
      indicate that TRPV6, NCX1, and CaBP-9k in the fetal placenta and CaBP-28k in the
      maternal placenta may play key roles in controlling calcium transport across the
      placenta during pregnancy.

PMID- 22407926
TI  - Measurement of generation-dependent proliferation rates and death rates during
      mouse erythroid progenitor cell differentiation.
AB  - Herein, we describe an experimental and computational approach to perform
      quantitative carboxyfluorescein diacetate succinimidyl ester (CFSE) cell-division
      tracking in cultures of primary colony-forming unit-erythroid (CFU-E) cells, a
      hematopoietic progenitor cell type, which is an important target for the
      treatment of blood disorders and for the manufacture of red blood cells. CFSE
      labeling of CFU-Es isolated from mouse fetal livers was performed to examine the
      effects of stem cell factor (SCF) and erythropoietin (EPO) in culture. We used a
      dynamic model of proliferation based on the Smith-Martin representation of the
      cell cycle to extract proliferation rates and death rates from CFSE time-series.
      However, we found that to accurately represent the cell population dynamics in
      differentiation cultures of CFU-Es, it was necessary to develop a model with
      generation-specific rate parameters. The generation-specific rates of
      proliferation and death were extracted for six generations (G(0) -G(5) ) and they
      revealed that, although SCF alone or EPO alone supported similar total cell
      outputs in culture, stimulation with EPO resulted in significantly higher
      proliferation rates from G(2) to G(5) and higher death rates in G(2) , G(3) , and
      G(5) compared with SCF. In addition, proliferation rates tended to increase from
      G(1) to G(5) in cultures supplemented with EPO and EPO + SCF, while they remained
      lower and more constant across generations with SCF. The results are consistent
      with the notion that SCF promotes CFU-E self-renewal while EPO promotes CFU-E
      differentiation in culture.

PMID- 22407927
TI  - Peroxisome proliferator-activated receptor (PPAR alpha/gamma) agonists as a
      potential target to reduce cardiovascular risk in diabetes.
AB  - The disappointing results of glucose lowering studies have highlighted the
      ongoing need to develop new therapeutic strategies to reduce cardiovascular risk
      in patients with type 2 diabetes. The presence of a range of metabolic
      abnormalities in diabetic patients presents a number of potential targets for
      therapeutic intervention. While modulation of peroxisome proliferator activated
      receptors (PPARs) represents an attractive approach, the results of studies of
      pharmacological agonists have been variable. The findings of these studies and
      rationale for development of dual PPAR-alpha/gamma agonists will be reviewed.

PMID- 22407928
TI  - Synthesis of hindered anilines: copper-catalyzed electrophilic amination of aryl
      boronic esters.
AB  - No longer a hindrance: copper-catalyzed electrophilic amination of aryl boronic
      esters is accomplished under mild reaction conditions using 2.5-5.0 mol % of a
      catalyst derived from copper tert-butoxide and Xantphos ligand. The reaction
      tolerates a wide range of functional groups and can be used to prepare some of
      the most hindered anilines made to date.

PMID- 22407929
TI  - Safe use of allopurinol and low-dose mercaptopurine therapy during pregnancy in
      an ulcerative colitis patient.

PMID- 22407930
TI  - Prospective change control analysis of transfer of platelet concentrate
      production from a specialized stem cell transplantation unit to a blood
      transfusion center.
AB  - BACKGROUND AND OBJECTIVES: Specialized centers claim a need for blood component
      production independent from the general blood transfusion services. We performed
      a prospective change control analysis of the transfer of platelet (PLT)
      production for hematological patients at the University Hospital Basel from the
      Department of Hematology to the Blood Transfusion Centre, Swiss Red Cross, Basel
      in February 2006. We wanted to demonstrate that neither quality nor transfusion
      outcome was affected. MATERIAL AND METHODS: Production quantity and efficiency,
      product quality and transfusion outcome were systematically recorded. A 2-year
      pretransfer period was compared to a 2 year post-transfer period. RESULTS: After
      transfer production quantity at the Blood Transfusion Centre increased from 4,483
      to 6,190 PLT concentrates. Production efficiency increased with a significant
      decrease in the rate of expired products (18% vs. 8%; P < 0.001). Product quality
      showed a slight decrease in median PLT count per unit (2.84 vs. 2.75 * 10(11); P
      < 0.001) and a slight increase in mean storage time prior to transfusion (3.18
      vs. 3.30 days; P < 0.001). Transfusion outcome measured as median corrected count
      increment one hour post-transfusion (10.5 vs. 10.7; P = 0.3) and the rate of
      patients with inadequate post-transfusion increment (31.5% vs. 32.1%; P = 0.6)
      did not differ. CONCLUSION: Supply and quality of PLT products was maintained
      after the transfer of PLT production to the Blood Transfusion Centre. An
      optimization of the supply chain process with markedly decreased expiration rates
      was achieved. These results argue against the need of specialized PLT production
      sites for selected patient groups.

PMID- 22407931
TI  - Clinical usefulness of low-dose dobutamine stress real-time myocardial contrast
      echocardiography for detection of viable myocardium.
AB  - OBJECTIVES: To evaluate and compare the diagnostic accuracy of semi-quantitative
      and quantitative real-time myocardial contrast echocardiography (RT-MCE) with low
      dose dobutamine stress echocardiography (LD-DSE) in detecting viable myocardium.
      METHODS: Thirty in-patients with coronary artery disease and regional wall motion
      abnormalities underwent RT-MCE without and with LD-DSE. Percutaneous coronary
      intervention was performed within 1 week after RT-MCE in all patients. Myocardial
      perfusion was evaluated from A, beta, and A * beta indices from microbubble
      replenishment curves. The motion of each myocardium segment was observed by
      routine echocardiography 1, 3, and 6 months after percutaneous coronary
      intervention and its improvement over time was the criterion of viable
      myocardium. RESULTS: RT-MCE sensitivity and specificity for the assessment of
      viable myocardium were 71.7% and 69.8%, rising to 81.3% and 76.7% (p < 0.05) when
      combined with LD-DSE. Using quantitative RT-MCE with cutoff values of A, beta,
      and A * beta, the sensitivity and specificity were 75.6%, 78.8%, 82.1%, and
      82.4%, 77.9%, 78.6%, respectively. When combined with LD-DSE, the sensitivity and
      specificity were 86.0%, 83.2%; 88.9% and 84.1%; 89.6%, 79.9%, respectively.
      CONCLUSIONS: Quantitative RT-MCE analysis yielded higher sensitivity and
      specificity than semi-quantitative RT-MCE with or without LD-DSE for the
      detection of viable myocardium.

PMID- 22407932
TI  - Subchronic hepatotoxicity evaluation of bromobenzene in Fischer 344 rats.
AB  - Male Fischer 344 (F344) rats were exposed to bromobenzene (BB) for 5 days and 2,
      4 and 13 weeks. BB was administered by gavage (corn oil vehicle) at doses of 0,
      25, 100, 200, 300 and 400 mg kg(-1) per day. Endpoints evaluated included
      clinical observations, body weights, liver weights, serum chemistry, blood BB,
      gross pathology and liver histopathology. There were no BB exposure-related
      clinical signs of toxicity. Mean body weight decreased by 5-10% compared with
      control in the 400 mg kg(-1) per day group. Liver weight increases were dose- and
      exposure time-related and statistically significant at >=25 mg kg(-1) per day.
      Incidence and severity of centrilobular cytoplasmic alteration and hepatocyte
      hypertrophy were related to dose and exposure time. At early time points (5 days
      and 2 weeks), centrilobular inflammation, including granulomatous areas, and
      necrotic and anisokaryocytic hepatocytes were observed in rats of the two highest
      BB dose groups. Blood BB concentrations increased linearly with dose and at 13
      weeks ranged from 8 to 136 ug ml(-1) (25-400 mg kg(-1) per day). In conclusion,
      rats administered BB doses up to 400 mg kg(-1) per day for up to 13 weeks had
      mild liver effects. A NOAEL of 200 mg kg(-1) per day was selected based on the
      statistically significant incidence of hepatocyte hypertrophy at doses >= 400 mg
      kg(-1) per day.

PMID- 22407933
TI  - Controlling reversible dielectric breakdown in metal/polymer nanocomposites.
AB  - Composites comprising metal nanorods encased in a polymer matrix exhibit
      reversible electric breakdown and can be cycled between low- and high-conductance
      states multiple times without permanent damage to the material. The voltage at
      which the breakdown occurs can be adjusted by engineering the properties of the
      polymeric matrix, in particular by doping the polymer with dipole-possessing
      additives whose role is to screen the applied electric fields.

PMID- 22407934
TI  - Anesthesia for liver transplantation in US academic centers: institutional
      structure and perioperative care.
AB  - Investigators at a single institution have shown that the organization of the
      anesthesia team influences patient outcomes after liver transplant surgery.
      Little is known about how liver transplant anesthesiologists are organized to
      deliver care throughout the United States. Therefore, we collected quantitative
      survey data from adult liver transplant programs in good standing with national
      governing agencies so that we could describe team structure and duties.
      Information was collected from 2 surveys in a series of quantitative surveys
      conducted by the Liver Transplant Anesthesia Consortium. All data related to
      duties, criteria for team membership, interactions/communication with the
      multidisciplinary team, and service availability were collected and summarized.
      Thirty-four of 119 registered transplant centers were excluded (21 pediatric
      centers and 13 centers not certified by national governing agencies). Private
      practice sites (26) were later excluded because of a poor response rate. There
      were minimal changes in the compositions of the programs between the 2 surveys.
      All academic programs had distinct liver transplant anesthesia teams. Most had
      set criteria for membership and protocols outlining the preoperative evaluation,
      attended selection committees, and were always available for transplant surgery.
      Fewer were involved in postoperative care or were available for patients needing
      subsequent surgery. Most trends were associated with the center volume. In
      conclusion, some of the variance in team structure and responsibilities is
      probably related to resources available at the site of practice. However,
      similarities in specific duties across all teams suggest some degree of self
      initiated specialization.

PMID- 22407935
TI  - A new, highly conductive, lithium salt/nonionic surfactant, lyotropic liquid
      crystalline mesophase and its application.

PMID- 22407939
TI  - Low-energy fractures of the humeral shaft and bisphosphonate use.
AB  - Atypical fractures of the femur have been reported to occur in patients on long
      term treatment with bisphosphonates; however, causality has not been proven, and
      it is not known whether similar fractures may occur in other long bones. We
      addressed this issue by examining the relationship between humeral shaft
      fractures and bisphosphonate use. We identified all patients aged >=50 years
      consecutively admitted to a single center with a new fracture of the humerus. All
      individual radiographs were examined and fracture site was classified. A case
      control study was undertaken in patients with humeral shaft fractures, and
      controls were sex- and age-matched patients with proximal humeral fractures in a
      1:4 ratio. Patients with shaft fractures and radiographic characteristics similar
      to those of atypical femoral fractures were compared with those with ordinary
      shaft fractures. The association between "atypical" fractures and bisphosphonate
      or glucocorticoid use was examined. A total of 198 patients had a low-energy
      fracture of the humerus; 20 of these patients had a shaft fracture (10%). These
      20 patients (cases) were matched with 80 patients with proximal fractures
      (controls). Bisphosphonates were used by 5% of cases and by 6.3% of controls
      (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.09-6.85); glucocorticoids
      were used by 10% of cases and 8.8% of controls (OR, 1.15; 95% CI, 0.23-5.83).
      There was no difference in cortical thickness between cases and controls and
      bisphosphonate or glucocorticoid users and nonusers. Four of the 20 patients with
      shaft fractures had "atypical" radiographic features, with significantly
      increased cortical thickness, but none of these had ever been treated with
      bisphosphonates or glucocorticoids. Our results show that low-energy fractures of
      the humeral shaft with "atypical" radiographic characteristics are infrequent and
      are not associated with the use of bisphosphonates or glucocorticoids.

PMID- 22407940
TI  - Lipid biomarkers of glioma cell growth arrest and cell death detected by 1 H
      magic angle spinning MRS.
AB  - Biomarkers of early response to treatment have the potential to improve cancer
      therapy by allowing treatment to be tailored to the individual. Alterations in
      lipids detected by in vivo MRS have been suggested as noninvasive biomarkers of
      cell stress and early indicators of cell death. An improved understanding of the
      relationship between MRS lipids and cell stress in vitro would aid in the
      translation of this technique into clinical use. Rat BT4C glioma cells were
      treated with 50 u m cis-dichlorodiammineplatinum II (cisplatin), a commonly used
      chemotherapeutic agent, and harvested at several time points up to 72 h. High
      resolution magic angle spinning (1) H MRS of cells was then performed on a 600
      MHz NMR spectrometer. The metabolites were quantified using a time domain fitting
      method, TARQUIN. Increases were detected in saturated and polyunsaturated fatty
      acid resonances early during the exposure to cisplatin. The fatty acid CH(2)
      /CH(3) ratio was unaltered by treatment after allowing for contributions of
      macromolecules. Polyunsaturated fatty acids increased on treatment, with the
      group -CH=CH-CH(2) -CH=CH- accounting for all the unsaturated fatty acid signals.
      Transmission electron microscopy, in addition to Nile red and 4',6-diamino-2
      phenylindole co-staining, revealed that the lipid increase was associated with
      cytoplasmic neutral lipid droplets. Small numbers of apoptotic and necrotic cells
      were detected by trypan blue, annexin V-fluorescein isothiocyanate-labelled flow
      cytometry and DNA laddering after up to 48 h of cisplatin exposure. Propidium
      iodide flow cytometry revealed that cells accumulated in the G1 stage of the cell
      growth cycle. In conclusion, an increase in the size of the lipid droplets is
      detected in morphologically viable cells during cisplatin exposure. (1) H MRS can
      detect lipid alterations during cell cycle arrest and progression of cell death,
      and has the potential to provide a noninvasive biomarker of treatment efficacy in
      vivo.

PMID- 22407941
TI  - The application of multiplex PCR to detect seven different DNA targets in group B
      streptococci.
AB  - Group B Streptococcus (GBS) causes severe infections in infants and in
      immunocompromised adults. GBS pathogenicity varies between and within serotypes,
      with considerable variation in genetic content between strains. For this reason,
      it is important to be able to carry out immediate and comprehensive diagnostics
      of these infections. Seven genes important for screening of GBS infection were
      detected: cfb gene encoding the CAMP factor presented in every GBS; the cps
      operon genes such as cps1aH, cps1a/2/3IJ, and cps5O specific for capsular
      polysaccharide types Ia, III, and V, respectively; macrolide resistance genes
      ermB and mefA/E; and the gbs2018 S10 region specific for ST17 hypervirulent
      clone. Standardization of multiplex PCR with the use of seven primer pairs was
      performed on 81 bacterial strains representing different GBS isolates (n = 75)
      and other Gram-positive cocci (n = 10). Multiplex PCR can be used as an effective
      screening method to detect different sequences important for the screening of GBS
      infection.

PMID- 22407942
TI  - mTOR is required for asymmetric division through small GTPases in mouse oocytes.
AB  - Mammalian target of rapamycin (mTOR) is central to the control of cell
      proliferation, growth, and survival in mammalian cells. Prolonged treatment with
      rapamycin inhibits mTOR complex 2 (mTORC2) activity, and both the mTORC1-mediated
      S6K1 and 4E-BP1/eIF4E pathways are essential for TORC2-mediated RhoA, Cdc42, and
      Rac1 expression during cell motility and F-actin reorganization. The functions of
      mTOR in the mouse oocyte remain unclear, however. The present study shows that
      rapamycin affects mTOR expression and cytoskeleton reorganization during meiotic
      maturation of mouse oocytes. mTOR mRNA was expressed in germinal vesicles (GV)
      until metaphase I (MI), and increased during metaphase II (MII). Immunostaining
      showed that mTOR localized around the spindle and in the cytoplasm of oocytes.
      Treatment of oocytes with rapamycin decreased mTOR at the RNA and protein level,
      and altered asymmetric division. Formation of the actin cap and the cortical
      granule-free domain were also disrupted after rapamycin treatment, indicating the
      failure of spindle migration. Injection of an anti-mTOR antibody yielded results
      consistent with those obtained for rapamycin treatment, further confirming the
      involvement of mTOR in oocyte polarity. Furthermore, rapamycin treatment reduced
      the mRNA expression of small GTPases (RhoA, Cdc42, and Rac1), which are crucial
      regulatory factors for cytoskeleton reorganization. Taken together, these results
      suggest that rapamycin inhibits spindle migration and asymmetric division during
      mouse oocyte maturation via mTOR-mediated small GTPase signaling pathways.

PMID- 22407943
TI  - ERBB2 overexpression triggers transient high mechanoactivity of breast tumor
      cells.
AB  - Biomechanical properties of tumor cells play an important role for the metastatic
      capacity of cancer. Cellular changes of viscoelastic features are prerequisite
      for cancer progression since they are essential for proliferation and metastasis.
      However, only little is known about the way how expression of oncogenes
      influences these biomechanical properties. To address this aspect we used a
      breast cancer cell line with inducible expression of an oncogenic version of
      ERBB2. ERBB2 is known to be correlated with bad prognosis in breast cancer. Cell
      elasticity was determined by the Optical Stretcher, where suspended cells are
      deformed by two slightly divergent laser beams. We found that induction of ERBB2
      caused remarkable biomechanical alterations of the MCF-7 cells after 24 h: the
      cells actively contracted in response to mechanical stimuli, a phenomenon known
      as mechanoactivation. After this period, as the cells became senescent, the
      mechanoactivity returned to control levels. Time-resolved gene array analysis
      revealed that mechanoactivation was accompanied by temporal upregulation of 46
      cytoskeletal genes. A possible role of these genes in tumor progression was
      investigated by expression analyses of 766 breast cancer patients. This showed an
      association of 12 out of these 46 genes with increased risk of metastasis. Our
      results demonstrate that overexpression of ERBB2 causes mechanoactivation of
      tumor cells, which may enhance tumor cell motility fostering distant metastasis.

PMID- 22407944
TI  - Longitudinal stability of binge-eating type in eating disorders.
AB  - OBJECTIVE: The purpose of this study was to examine the 2-year longitudinal
      stability of objective bulimic (binge eating) episodes (OBEs) and subjective
      bulimic (binge eating) episodes (SBEs) in a multisite eating disorders sample.
      METHOD: Participants included 288 females with eating disorder symptoms who were
      assessed every 6 months using the Eating Disorder Examination. RESULTS: Markov
      modeling revealed considerable longitudinal variability between types of binge
      eating over 6-month time intervals with relatively higher probability estimates
      for consistency between OBEs and SBEs than specific transitions between types for
      the overall sample as well as for eating disorder diagnostic groups. Transition
      patterns examining all five time points indicated notable variability in binge
      eating patterns among participants. DISCUSSION: These findings suggest that
      although longitudinal patterns of binge types are variable among individuals with
      eating disorders, consistency in OBEs and SBEs was the most common pattern
      observed.

PMID- 22407945
TI  - Photocatalytic water reduction and study of the formation of Fe(i)Fe(0) species
      in diiron catalyst systems.
AB  - Noble-metal-free systems with bio-inspired diiron dithiolate mimics of the [FeFe]
      hydrogenase active site, namely, [(MU-pdt)Fe(2) (CO)(5) L]
      [pdt=propanedithiolate; L=P(CH(2) OH)(3) (1), P(CH(3) )(3) (2)], as water
      reduction catalysts with xanthene dyes as photosensitizers and triethylamine as a
      sacrificial electron donor were studied for visible-light-driven water reduction
      to hydrogen. These systems display good catalytic activities with the
      efficiencies in hydrogen evolution of up to 226 turnovers for 1, if Eosin Y was
      used as the photosensitizer in an environmentally benign solvent (EtOH/H(2) O)
      after 15 h of irradiation (lambda>450 nm) under optimal conditions. Under all of
      the conditions adopted, 1 that has a water soluble phosphine ligand, P(CH(2)
      OH)(3) displayed a higher efficiency than 2, which bears a PMe(3) ligand. The
      photoinduced electron transfer in the systems was studied using fluorescence,
      transient absorption, time-resolved UV/Vis, and in situ electron paramagnetic
      resonance (EPR) spectroscopy. A new electron-transfer mechanism is proposed for
      hydrogen evolution by these iron-based photocatalytic systems.

PMID- 22407946
TI  - Transarterial chemoembolization for hepatocellular carcinoma over three decades:
      current progress and perspective.
AB  - Transcatheter arterial chemoembolization has been performed worldwide for
      patients with unresectable hepatocellular carcinoma for three decades. After long
      controversy, survival benefit was revealed by two randomized controlled trials.
      In Japan, chemoembolization accounted for initial treatment of 32% of patients
      and 58% for recurrent foci. The indications of chemoembolization are various:
      they are multinodular tumors in the Barcelona Clinic Liver Cancer staging system
      and two or three tumors >3 cm or four or more tumors in the Japanese guidelines,
      and both indications fulfill the Child-Pugh Class A/B or liver damage A/B and
      exclusion of vascular invasion or extrahepatic spread. Recently, both guidelines
      were identified to have almost similar content. The 4966 patients stratified to
      chemoembolization recommended by the Japanese guidelines showed that 3-year
      survival of patients with two or three tumors >3 cm or four or more tumors was 55
      and 46% in Child-Pugh A, respectively, and 30 and 22% in Class B, respectively.
      These results would help in comparing the outcome of chemoembolization in the
      different backgrounds of the East and West. The modified Response Evaluation
      Criteria in Solid Tumor guideline is now proposed to cover the deficiency of
      Response Evaluation Criteria in Solid Tumor to evaluate the response to
      chemoembolization. Recently, chemoembolization with drug-eluting beads and
      radioembolization with yttrium-90 microspheres have been introduced, and each of
      them showed similar tumor response and median survival compared with conventional
      chemoembolization. Moreover, the combination of chemoembolization and molecular
      targeted agent is now on-going to evaluate the synergistic effect.

PMID- 22407947
TI  - Developmental exposure to manganese chloride induces sustained aberration of
      neurogenesis in the hippocampal dentate gyrus of mice.
AB  - The effect of exogenously administered manganese (Mn) on developmental
      neurogenesis in the hippocampal dentate gyrus was examined in male mice after
      maternal exposure to MnCl(2) (0, 32, 160, or 800 ppm as Mn in diet) from
      gestational day 10 to day 21 after delivery on weaning. Immunohistochemistry was
      performed to monitor neurogenesis and interneuron subpopulations on postnatal
      days (PNDs) 21 and 77 (adult stage). Reelin-synthesizing gamma-aminobutyric acid
      (GABA)ergic interneurons increased in the hilus with >= 160 ppm on weaning to
      sustain to PND 77 at 800 ppm. Apoptosis in the neuroblast-producing subgranular
      zone increased with 800 ppm and TUC4-expressing immature granule cells decreased
      with 800 ppm on weaning, whereas at the adult stage, immature granule cells
      increased. On PND 21, transcript levels increased with Reln and its receptor gene
      Lrp8 and decreased with Dpysl3 coding TUC4 in the dentate gyrus, confirming
      immunohistochemical results. Double immunohistochemistry revealed a sustained
      increase of reelin-expressing and NeuN-lacking or weakly positive immature
      interneurons and NeuN-expressing mature neurons in the hilus through to the adult
      stage as examined at 800 ppm. Brain Mn concentrations increased at both PNDs 21
      and 77 in all MnCl(2)-exposed groups. These results suggest that Mn targets
      immature granule cells causing apoptosis and neuronal mismigration. Sustained
      increases in immature reelin-synthesizing GABAergic interneurons may represent
      continued aberration in neurogenesis and following migration to cause an
      excessive response for overproduction of immature granule cells through to the
      adult stage. Sustained high concentration of Mn in the brain may be responsible
      for these changes.

PMID- 22407948
TI  - Epigenetic alterations may regulate temporary reversal of CD4(+) T cell
      activation caused by trichloroethylene exposure.
AB  - Previous studies have shown that short-term (4 weeks) or chronic (32 weeks)
      exposure to trichloroethylene (TCE) in drinking water of female MRL+/+ mice
      generated CD4(+) T cells that secreted increased levels of interferon (IFN)-gamma
      and expressed an activated (CD44(hi)CD62L(lo)) phenotype. In contrast, the
      current study of subchronic TCE exposure showed that midway in the disease
      process both of these parameters of CD4(+) T cell activation were reversed. This
      phase of the disease process may represent an attempt by the body to counteract
      the inflammatory effects of TCE. The decrease in CD4(+) T cell production of IFN
      gamma following subchronic TCE exposure could not be attributed to skewing toward
      a Th2 or Th17 phenotype or to an increase in Treg cells. Instead, the suppression
      corresponded to alterations in markers used to assess DNA methylation, namely
      increased expression of retrotransposons Iap (intracisternal A particle) and
      Muerv (murine endogenous retrovirus). Also observed was an increase in the
      expression of Dnmt1 (DNA methyltransferase-1) and decreased expression of several
      genes known to be downregulated by DNA methylation, namely Ifng, Il2, and Cdkn1a.
      CD4(+) T cells from a second study in which MRL+/+ mice were treated for 17 weeks
      with TCE showed a similar increase in Iap and decrease in Cdkn1a. In addition,
      DNA collected from the CD4(+) T cells in the second study showed TCE-decreased
      global DNA methylation. Thus, these results described the biphasic nature of TCE
      induced alterations in CD4(+) T cell function and suggested that these changes
      represented potentially reversible alterations in epigenetic processes.

PMID- 22407949
TI  - Perceptions of the painful body: the relationship between body perception
      disturbance, pain and tactile discrimination in complex regional pain syndrome.
AB  - BACKGROUND: Disturbances in body perception are increasingly acknowledged as a
      feature of complex regional pain syndrome (CRPS). Conventional treatments have
      limited success particularly among those with long-standing disease.
      Understanding the relationship between body perception disturbance, pain and
      tactile acuity might provide insight into alternative avenues for treatment. The
      aim of this study was to test the hypotheses that (1) body perception disturbance
      is positively related to pain and (2) decreased tactile acuity is related to
      increased body perception disturbance. METHODS: A controlled observational design
      was used to measure these features among those with CRPS of one arm. The extent
      of body perception disturbance was assessed using the Bath CRPS body perception
      disturbance scale and pain was measured using the neuropathic pain symptom
      inventory. Two-point discrimination threshold testing was performed as a measure
      of tactile acuity. RESULTS: Findings confirmed both hypotheses. Body perception
      disturbance was found to positively correlate with pain such that those in
      greater pain had more extensive body perception disturbance (r = 0.57, p < 0.01).
      Furthermore, a positive correlation was revealed between body perception
      disturbance and two-point discrimination thresholds (r = 0.5, p < 0.025) so those
      with greater body perception disturbance had worse tactile acuity. Interestingly,
      those with longer disease duration had significantly greater body perception
      disturbance (r = 0.66, p < 0.001). CONCLUSION: Aberrant central processing is
      suggested as the neural correlate of body perception disturbance and tactile
      impairment. The exact relationship between body perception disturbance, pain and
      tactile acuity and how they may be modulated for pain relief requires further
      exploration.

PMID- 22407950
TI  - A novel and rapid apoptosis assay based on thiol redox status.
AB  - We present here a novel probe, VitaBright-48, for the evaluation of the cellular
      level of reduced thiols. Using different cell lines and apoptogenic agents we
      show that a decrease in the level of reduced thiols correlates with well-known
      apoptotic markers such as phosphatidylserine translocation and caspase activity.
      The cell population to be investigated is added to the nonfluorescent stain
      VitaBright-48, which immediately permeates the cell membrane and reacts with
      intracellular thiols, forming a fluorescent compound. Quantification of the cell
      fluorescence directly after staining (without washing) can then be used to
      determine the population's cellular thiol level at the single cell level. Based
      on the results presented here, we suggest that measurement of changes in the
      level of free thiols should be added to the list of phenotypes which may be
      investigated in order to detect apoptosis.

PMID- 22407951
TI  - Peak and time-integrated shear rates independently predict flow-mediated
      dilation.
AB  - BACKGROUND: To determine whether peak and time-integrated shear rates
      independently predict flow-mediated dilation (FMD). METHODS: Eleven physically
      active (25 +/- 5 years old) male subjects were tested. FMD was defined as the
      shear rate-diameter relationship. Hierarchical linear modeling was used to
      estimate brachial artery diameter change with repeated measures of shear rate
      nested within each subject. Two models were tested: 1) FMD was induced using
      ischemia-induced hyperemia (2, 4, 6, and 10 minutes); and 2) FMD was induced
      following transient (ischemia) and steady-state (forearm heating and handgrip
      exercise) increases in shear rate. For both models we determined whether peak, in
      addition to time-integrated shear rates, explained a significant portion of
      variation for diameter change. RESULTS: Model 1: Time integrated shear rates
      explained most of the variation for diameter change. However, peak shear rate
      explained an additional significant portion of variation. Model 2: The transient
      condition resulted in significantly (p = 0.012) smaller diameter change per shear
      rate change than the steady-state condition. However, when specifying peak shear
      rate as a covariate, the difference between conditions became nonsignificant (p =
      0.138). CONCLUSIONS: Peak and time-integrated shear rates independently predict
      FMD. Future studies using the FMD test should consider both parameters.

PMID- 22407952
TI  - Ethanol consumption modifies the body turnover of cadmium: a study in a rat model
      of human exposure.
AB  - Ethanol (Et) abusers may also be exposed to excessive amounts of cadmium (Cd).
      Thus, the study was aimed at estimating the influence of Et on the body turnover
      of Cd in a rat model reflecting excessive alcohol consumption in humans
      chronically exposed to moderate and relatively high levels of this metal. For
      this purpose, Cd apparent absorption, retention in the body and concentration in
      the blood, stomach, duodenum, liver, kidney, spleen, brain, heart, testis and
      femur as well as its fecal and urinary excretion in the rats exposed to 5 and
      50mg Cd l(-1) (in drinking water; for 16 weeks from the fifth week of the
      animal's life) and/or Et (5 g kg(-1) b.w. per 24 h, by oral gavage; for 12 weeks
      from the ninth week of life) were estimated. Moreover, the duodenal, liver and
      kidney pool of the nonmetallothionein (Mt)-bound Cd was evaluated. The
      administration of Et during the exposure to 5 or 50mg Cd l(-1) increased Cd
      accumulation in the gastrointestinal tract and its urinary excretion, and
      decreased Cd concentration in the blood, femur and numerous soft tissues
      (including liver and kidney) as well as the total pool of this metal in internal
      organs. Et modified or not the pool of the non-Mt-bound Cd, depending on the
      level of treatment with this metal. The results show that excessive Et
      consumption during Cd exposure may decrease the body burden of this metal, at
      least partly, by its lower absorption and increased urinary excretion. Based on
      this study, it can be concluded that Cd concentration in the blood and tissues of
      alcohol abusers chronically exposed to moderate and relatively high levels of
      this metal may be lower, whereas its urinary excretion is higher than in their
      nondrinking counterparts. However, since Et is toxic itself, the decreased body
      burden of Cd owing to alcohol consumption does not allow for the conclusion that
      the risk of health damage may be lower at co-exposure to these xenobiotics. In a
      further study, it will be investigated how the Et-induced changes in the body
      status of Cd influence the effects of its toxic action.

PMID- 22407953
TI  - Optimizing the charge balance of fluorescent organic light-emitting devices to
      achieve high external quantum efficiency beyond the conventional upper limit.
AB  - The external quantum efficiencies (EQEs) of fluorescent light emitting devices
      are drastically improved by optimizing the charge balance. When N,N'
      di(naphthalene-1-yl)- N,N'-diphenylbenzidine (NPD) is used as a hole-transporting
      layer (HTL) and Alq(3)  as an electron-transporting layer (ETL) with the green
      dopant 2,3,6,7-tetrahydro-1,1,7,7-tetramethyl-1H,5H,11H-10-(2
      benzothiazolyl)quinolizino-[9,9a,1gh]coumarin (C545T), the EQE is observed to be
      approximately 3%. However, when the HTL and ETL materials are optimized, a 7.5%
      external quantum efficiency (EQE) in a green-emitting device and an 8.2% EQE in a
      blue-emitting device are achieved at 100 cd m(-2) .

PMID- 22407954
TI  - Photoactivated directionally controlled transit of a non-symmetric molecular axle
      through a macrocycle.

PMID- 22407955
TI  - Quality and sensory acceptability of a chilled functional apple ready-dessert.
AB  - An apple and dairy based ready-dessert with an added prebiotic was stored and
      chill temperatures and number of quality attributes were monitored during chill
      (4  degrees C) storage for 30 days. All ready-desserts were thermally processed
      by sous vide (P (90) > 10 min). The stability of the dairy component in ready
      desserts was monitored by measuring volatile free fatty acids. Changes in these
      components were more evident in prebiotic-enriched samples compared to controls.
      However, no significant differences were observed over storage in control and
      prebiotic-enriched ready-desserts. This was supported by sensory analysis that
      showed no significant changes over storage in control or prebiotic-enriched
      samples. Of the other quality parameters, the addition of prebiotic inclusions
      resulted in lower L and b values and dry matter (p < 0.05), while increasing (p <
      0.05) soluble solids content compared to control samples. Fluctuations in some of
      the quality parameters were also observed over storage. Rheological
      characteristics, i.e. flow behaviour (n), consistency index (K), storage (G'),
      loss (G") and complex (G*) moduli were unaffected by prebiotic inclusion.
      However, storage affected the rheological characteristics of ready-desserts. A
      decrease (p < 0.05) in flow behaviour (n) led to concomitant increases in
      consistency index (K) and complex modulus (G*) values in control samples.

PMID- 22407956
TI  - Deletion of beta-adrenergic receptor 1, 2, or both leads to different bone
      phenotypes and response to mechanical stimulation.
AB  - As they age, mice deficient for the beta2-adrenergic receptor (Adrb2(-/-) )
      maintain greater trabecular bone microarchitecture, as a result of lower bone
      resorption and increased bone formation. The role of beta1-adrenergic receptor
      signaling and its interaction with beta2-adrenergic receptor on bone mass
      regulation, however, remains poorly understood. We first investigated the
      skeletal response to mechanical stimulation in mice deficient for beta1
      adrenergic receptors and/or beta2-adrenergic receptors. Upon axial compression
      loading of the tibia, bone density, cancellous and cortical microarchitecture, as
      well as histomorphometric bone forming indices, were increased in both Adrb2(-/-)
      and wild-type (WT) mice, but not in Adrb1(-/-) nor in Adrb1b2(-/-) mice.
      Moreover, in the unstimulated femur and vertebra, bone mass and microarchitecture
      were increased in Adrb2(-/-) mice, whereas in Adrb1(-/-) and Adrb1b2(-/-) double
      knockout mice, femur bone mineral density (BMD), cancellous bone volume/total
      volume (BV/TV), cortical size, and cortical thickness were lower compared to WT.
      Bone histomorphometry and biochemical markers showed markedly decreased bone
      formation in Adrb1b2(-/-) mice during growth, which paralleled a significant
      decline in circulating insulin-like growth factor 1 (IGF-1) and IGF-binding
      protein 3 (IGF-BP3). Finally, administration of the beta-adrenergic agonist
      isoproterenol increased bone resorption and receptor activator of NF-kappaB
      ligand (RANKL) and decreased bone mass and microarchitecture in WT but not in
      Adrb1b2(-/-) mice. Altogether, these results demonstrate that beta1- and beta2
      adrenergic signaling exert opposite effects on bone, with beta1 exerting a
      predominant anabolic stimulus in response to mechanical stimulation and during
      growth, whereas beta2-adrenergic receptor signaling mainly regulates bone
      resorption during aging.

PMID- 22407957
TI  - Lactate and glycine-potential MR biomarkers of prognosis in estrogen receptor
      positive breast cancers.
AB  - Breast cancer is a heterogeneous disease with a variable prognosis. Clinical
      factors provide some information about the prognosis of patients with breast
      cancer; however, there is a need for additional information to stratify patients
      for improved and more individualized treatment. The aim of this study was to
      examine the relationship between the metabolite profiles of breast cancer tissue
      and 5-year survival. Biopsies from breast cancer patients (n=98) were excised
      during surgery and analyzed by high-resolution magic angle spinning MRS. The data
      were analyzed by multivariate principal component analysis and partial least
      squares discriminant analysis, and the findings of important metabolites were
      confirmed by spectral integration of the metabolite peaks. Predictions of 5-year
      survival using metabolite profiles were compared with predictions using clinical
      parameters. Based on the metabolite profiles, patients with estrogen receptor
      (ER)-positive breast cancer (n=71) were separated into two groups with
      significantly different survival rates (p=0.024). Higher levels of glycine and
      lactate were found to be associated with lower survival rates by both
      multivariate analyses and spectral integration, and are suggested as biomarkers
      for breast cancer prognosis. Similar metabolic differences were not observed for
      ER-negative patients, where survivors could not be separated from nonsurvivors.
      Predictions of 5-year survival of ER-positive patients using metabolite profiles
      gave better and more robust results than those using traditional clinical
      parameters. The results imply that the metabolic state of a tumor may provide
      additional information concerning breast cancer prognosis. Further studies should
      be conducted in order to evaluate the role of MR metabolomics as an additional
      clinical tool for determining the prognosis of patients with breast cancer.

PMID- 22407958
TI  - Survey of diabetes risk assessment tools: concepts, structure and performance.
AB  - The objective of this study is to review the effectiveness and limitations of
      existing diabetes risk screening tools to assess the need for further developing
      of such tools. An electronic search of the EMBASE, MEDLINE, and Cochrane library
      supplemented by a manual search was performed from 1995-2010. The search
      retrieved a total of 2168 articles reporting diabetes risk assessment tools
      which, after culling, produced 41 tools developed in 22 countries, with the
      majority (n = 26) developed in North America and Europe. All are short
      questionnaires of 2-16 questions incorporating common variables including age,
      gender, waist circumference, BMI, family history of diabetes, history of
      hypertension or antihypertensive medications. While scoring format and cut-offs
      point are diverse between questionnaires, overall accuracy value range of 40-97%,
      24-86% and 62-87% were reported for sensitivity, specificity and receiver
      operating characteristic curve respectively. In summary, there is a trend of
      increasing availability of diabetes prediction tools with the existing risk
      assessment tools being generally a short questionnaire aiming for ease of use in
      clinical practice. The overall performance of existing tools showed moderate to
      high accuracy in their predictive performance. However, further detailed
      comparison of existing questionnaires is needed to evaluate whether they can
      serve adequately as diabetes risk assessment tool in clinical practice.

PMID- 22407959
TI  - Optimizing the perceived benefits and health outcomes of writing about traumatic
      life events.
AB  - Expressive writing, which involves disclosing one's deepest thoughts and feelings
      about a stressful life event by using a first-person perspective, has been linked
      to gains in health and well-being, though effect sizes range widely. Assuming a
      third-person perspective is a natural and effective way of coping with highly
      distressing events. Therefore, the current study examined whether a distanced,
      third-person approach to expressive writing might be more beneficial than a
      traditional, first-person intervention for high baseline levels of event-linked
      intrusive thinking. Randomly assigned participants wrote expressively about
      traumatic life events by using a first-person or third-person-singular
      perspective. Linguistic analyses showed that assuming a first-person perspective
      is linked to higher levels of in-text cognitive engagement, whereas a third
      person perspective is linked to lower cognitive engagement. However, in a context
      of higher levels of intrusive thinking, third-person expressive writing, relative
      to a traditional first-person approach, yielded (1) greater perceived benefits
      and positive, long-lasting effects as well as (2) fewer days of activity
      restriction due to illness. Although more research is needed, these results
      suggest that third-person expressive writing may be an especially fitting
      technique for recovering from traumatic or highly stressful life events.

PMID- 22407960
TI  - Guest-responsive reversible swelling and enhanced fluorescence in a super
      absorbent, dynamic microporous polymer.
AB  - A swell idea! The guest-responsive reversible swelling and fluorescence
      enhancement of a dynamic, microporous polymer network is presented. Guest-induced
      breathing of hydrophobic pores imparts multi-functional properties, such as super
      absorbency, phase-selective swelling of oil from water and encapsulation of C(60)
      (see figure), to this soft micro-porous organic polymer.

PMID- 22407962
TI  - BMP-2 immobilized on nanocrystalline diamond-coated titanium screws;
      demonstration of osteoinductive properties in irradiated bone.
AB  - BACKGROUND: Irradiation results in impaired bone healing. Thus, osteosynthesis
      procedures are afflicted with increased failure rates. To improve
      osseointegration bone morphogenetic protein-2 (BMP-2) immobilized on
      nanocrystalline diamond (NCD)-coated implant surfaces might be 1 solution.
      METHODS: By 4 weeks after irradiation of pig's mandible with a dose of 60 Gy a
      fracture was accomplished. Osteosynthesis was performed either with titanium
      osteosynthesis screws or NCD-coated screws with immobilized BMP-2. Nonirradiated
      animals served as control. After 1, 2, 4, and 8 weeks screws were evaluated
      histologically. Bone biopsies were gained to extract mesenchymal stem or
      precursor cells (MSCs). RESULTS: MSCs after irradiation demonstrated a behavior
      comparable to that of unirradiated cells. Consequently, immobilized BMP-2
      resulted in an initial increased bone contact ratio (p = .014) but demonstrated
      no sustainable effect compared with osseointegration in nonirradiated bone (p =
      .08). CONCLUSION: Immobilized BMP-2 demonstrates an osteoinductive effect in
      irradiated bone. MSCs as effector cells possess protective mechanisms to overcome
      the destructive effect of irradiation.

PMID- 22407963
TI  - Pain following stroke: a prospective study.
AB  - BACKGROUND: Post-stroke pain is common and affects the quality of life of stroke
      survivors, but the incidence and severity of headache, shoulder pain, other joint
      pain and central post-stroke pain following stroke still remain unclear. The aim
      of this prospective study was to determine the incidence and intensity of these
      different types of post-stroke pain. METHODS: A total of 299 consecutive stroke
      patients, admitted to the Department of Neurology at Aarhus University Hospital,
      underwent a structured interview and a short sensory examination within 4 days of
      admission. Follow-up was conducted by phone 3 and 6 months after stroke onset,
      with 275 patients completing the whole study. Pain with onset in relation to
      stroke onset or following stroke was defined as 'newly developed pain'. RESULTS:
      At the 6-month follow-up, newly developed pain was reported by 45.8% of the
      patients; headache by 13.1%, shoulder pain by 16.4%, other joint pain by 11.7%,
      other pain by 20.0% and evoked pain by light touch or thermal stimuli by 8.0%.
      More than one pain type was reported by 36.5% of the patients with newly
      developed pain. According to pre-defined criteria, 10.5% of the patients were
      classified as having possible central post-stroke pain. There was a moderate to
      severe impact on daily life in 33.6% of the patients with newly developed pain.
      CONCLUSIONS: Pain following stroke is common, with almost half of the patients
      reporting newly developed pain 6 months after stroke.

PMID- 22407961
TI  - The microtubule cytoskeleton is required for a G2 cell cycle delay in cancer
      cells lacking stathmin and p53.
AB  - In several cancer cell lines, depleting the microtubule (MT)-destabilizing
      protein stathmin/oncoprotein18 leads to a G2 cell cycle delay and apoptosis.
      These phenotypes are observed only in synergy with low levels of p53, but the
      pathway(s) activated by stathmin depletion to delay the cell cycle are unknown.
      We found that stathmin depletion caused greater MT stability in synergy with loss
      of p53, measured by the levels of acetylated alpha-tubulin and the rate of
      centrosomal MT nucleation. Nocodazole or vinblastine-induced MT depolymerization
      abrogated the stathmin-depletion induced G2 delay, measured by the percentage of
      cells staining positive for several markers (TPX2, CDK1 with inhibitory
      phosphorylation), indicating that MTs are required to lengthen G2. Live cell
      imaging showed that stathmin depletion increased time in G2 without an impact on
      the duration of mitosis, indicating that the longer interphase duration is not
      simply a consequence of a previous slowed mitosis. In contrast, stabilization of
      MTs with paclitaxel (8 nM) slowed mitosis without lengthening the duration of
      interphase, demonstrating that increased MT stability alone is not sufficient to
      delay cells in G2.

PMID- 22407964
TI  - DyeCycle Violet used for side population detection is a substrate of P
      glycoprotein.
AB  - Cancer stem cells (CSC) are increasingly recognized as key target cells for
      cancer therapy because they are both tumorigenic and chemoresistant and,
      therefore, can give rise to recurrent disease. Side population (SP) sorting using
      an ultraviolet (UV) laser is an established method to isolate CSC based on ABC
      drug transporter-dependent (e.g., ABCG2) Hoechst 33342 efflux. We here show that
      Vybrant(r) DyeCycleTM Violet (DCV), a DNA-binding fluorophor allowing SP sorting
      using a non-UV laser (such as violet laser), is transported via P-glycoprotein
      (PgP). Because PgP might be particularly abundant in multidrug-resistant cancer
      cells rather than bona fide CSC, investigators using DCV should be aware that
      this strategy might also detect PgP-expressing non-CSC.

PMID- 22407965
TI  - How many therapists? Practical guidance on investigating therapist effects in
      randomized controlled trials for eating disorders.
AB  - OBJECTIVE: An important question in implementation/dissemination research is
      whether the efficacy of a given treatment varies in part based on the therapist
      delivering the treatment. This study sought to provide practical guidance to
      researchers in the field of eating disorders for building measurement of
      therapist effects into the design of a typical, relatively small randomized
      controlled trial (RCT). METHOD: Using assumptions based on past trials of eating
      disorder treatments, Monte Carlo simulations were used to examine 12 different
      scenarios based on crossing the number of therapists (between two and five) and
      the estimated therapist effect size (small, medium, and large). Patient sample
      size and study design were held constant. RESULTS: There was reasonable power
      (>=70%) to detect the therapist effect with three or four therapists and a large
      effect size. DISCUSSION: Several practical implications for testing therapist
      effects in RCT are discussed.

PMID- 22407966
TI  - Selective production of 1,2-propylene glycol from Jerusalem artichoke tuber using
      Ni-W(2) C/AC catalysts.
AB  - A series of Ni-promoted W(2) C/activated carbon (AC) catalysts were investigated
      for the catalytic conversion of Jerusalem artichoke tuber (JAT) under
      hydrothermal conditions and hydrogen pressure. Even a small amount of Ni could
      greatly promote the conversion of JAT to 1,2-propylene glycol (1,2-PG), whereas
      the pure W(2) C/AC catalyst resulted in the selective formation of acetol. The
      product distribution profiles involving the reaction temperature, time, and H(2)
      pressure indicated that 1,2-PG formed as a result of acetol hydrogenation, which
      was catalyzed by Ni. Thus, there was a synergy between W(2) C and Ni, and the
      best performance yielded 38.5% of 1,2-PG over a 4%Ni-20%W(2) C/AC catalyst at 245
      degrees C, 6 MPa H(2) , and 80 min. To understand the reaction process, some
      important intermediates, such as inulin, fructose, acetol, glyceraldehyde, and
      1,3-dihydroxyacetone, were used as the feedstock. Based on the product
      distributions derived from these intermediates, a reaction pathway was proposed,
      where JAT was first hydrolyzed into a mixture of fructose and glucose under the
      catalysis of H(+) , then the sugars underwent a retro-aldol reaction followed by
      hydrogenation catalyzed by Ni-W(2) C.

PMID- 22407967
TI  - Apoptotic responses of zebrafish (Danio rerio) after exposure with microcystin-LR
      under different ambient temperatures.
AB  - Microcystins (MCs) can cause evident hepatic apoptosis. In vitro studies
      indicated that uptake of MC by isolated hepatocytes was dramatically reduced as
      ambient temperature dropped, and some studies presented a hypothesis that
      differences in core body temperatures in animals result in diverse uptake of MC,
      as well as different toxic effects. Thus far, however, few in vivo studies have
      been conducted to investigate the effects of temperature on MC-induced hepatocyte
      apoptosis in fish, a typical poikilotherm. In the present study, zebrafish were
      treated with MC-LR, an MC metabolite, at three water temperatures (12, 22 and 32 
      degrees C), and evident differences in apoptotic profiles were observed. Damage
      to liver ultrastructures revealed temperature-dependent early-stage patterns of
      apoptosis. Flow-cytometric analysis indicated that hepatocyte apoptotic rates
      varied with a temperature-dependent effect. The transcription levels of some
      apoptosis-related genes were determined using quantitative real-time polymerase
      chain reaction, and significantly elevated gene expressions of P53, Bcl-2, Bax
      and caspase-3 were found in the 12 and 32  degrees C groups. Results of the
      present study indicate that different ambient temperatures can lead to various
      toxic effects of MCs on hepatic apoptosis in fish.

PMID- 22407968
TI  - An in vivo spectral multiplexing approach for the cooperative imaging of
      different disease-related biomarkers with near-infrared fluorescent forster
      resonance energy transfer probes.
AB  - In recent years, much progress has been made in analyzing the molecular origin of
      many diseases in vivo. For most applications, attention has been devoted to the
      detection of single molecules only. In this study, we present a proof of concept
      for the straightforward monitoring of interactions between different molecules
      via Forster resonance energy transfer (FRET) in an in vivo spectral multiplexing
      approach using conventional small organic dyes covalently attached to antibodies.
      METHODS: We coupled the fluorophores DY-682 (donor; absorption [abs]/emission
      [em], 674/712 nm), DY-505 (control donor; abs/em, 498/529 nm), and DY-782
      (acceptor; abs/em, 752/795 nm) to the model antibody IgG. The occurrence of FRET
      between these fluorophores was assessed in vitro for conjugate mixtures adsorbed
      onto membranes, after accumulation into the phagocytic compartment of macrophages
      (J774 cells), and in vivo in a mouse edema model using a whole-body animal
      imaging system with multispectral analysis features. RESULTS: When the free
      acceptor DY-782 was combined with the DY-682 donor, FRET occurred as a
      consequence of small dye-to-dye distances, unlike the case for mixtures of the
      dyes DY-782 and DY-505. Our proof of concept was also transferred to living cells
      after internalization of the DY-682-IgG-DY-782-IgG pair into macrophages and
      finally to animals, where intermolecular FRET was observed after systemic probe
      application in vivo in edema-bearing mice. CONCLUSION: Our simple cooperative
      imaging approach enables the noninvasive detection of the presence of two or
      principally even more neighboring disease-related biomarkers. This finding is of
      high relevance for the in vivo identification of complex biologic processes
      requiring strong spatial interrelations of target molecules in key pathologic
      activation processes such as inflammation, cancer, and neurodegenerative
      diseases.

PMID- 22407969
TI  - Enhancement of photogenerated mechanical force in azobenzene-functionalized
      polyimides.

PMID- 22407970
TI  - Evaluation of trabecular microarchitecture in nonosteoporotic postmenopausal
      women with and without fracture.
AB  - This study compared microscopic magnetic resonance imaging (uMRI) parameters of
      trabecular microarchitecture between postmenopausal women with and without
      fracture who have normal or osteopenic bone mineral density (BMD) on dual-energy
      X-ray absorptiometry (DXA). It included 36 postmenopausal white women 50 years of
      age and older with normal or osteopenic BMD (T-scores better than -2.5 at the
      lumbar spine, proximal femur, and one-third radius on DXA). Eighteen women had a
      history of low-energy fracture, whereas 18 women had no history of fracture and
      served as an age, race, and ultradistal radius BMD-matched control group. A three
      dimensional fast large-angle spin-echo (FLASE) sequence with 137 um * 137 um *
      400 um resolution was performed through the nondominant wrist of all 36 women
      using the same 1.5T scanner. The high-resolution images were used to measure
      trabecular bone volume fraction, trabecular thickness, surface-to-curve ratio,
      and erosion index. Wilcoxon signed-rank tests were used to compare differences in
      BMD and uMRI parameters between postmenopausal women with and without fracture.
      Post-menopausal women with fracture had significantly lower (p < 0.05) trabecular
      bone volume fraction and surface-to-curve ratio and significantly higher (p <
      0.05) erosion index than postmenopausal women without fracture. There was no
      significant difference between postmenopausal women with and without fracture in
      trabecular thickness (p = 0.80) and BMD of the spine (p = 0.21), proximal femur
      (p = 0.19), one-third radius (p = 0.47), and ultradistal radius (p = 0.90).
      Postmenopausal women with normal or osteopenic BMD who had a history of low
      energy fracture had significantly different (p < 0.05) uMRI parameters than an
      age, race, and ultradistal radius BMD-matched control group of postmenopausal
      women with no history of fracture. Our study suggests that uMRI can be used to
      identify individuals without a DXA-based diagnosis of osteoporosis who have
      impaired trabecular microarchitecture and thus a heretofore-unappreciated
      elevated fracture risk.

PMID- 22407971
TI  - The difference of glucostatic parameters according to the remission of diabetes
      after Roux-en-Y gastric bypass.
AB  - BACKGROUND: Gut hormones play a role in diabetes remission after a Roux-en-Y
      gastric bypass (RYGB). Our aim was to investigate differences in gut hormone
      secretion according to diabetes remission after surgery. Second, we aimed to
      identify differences in insulin secretion and sensitivity according to diabetes
      remission after RYGB. METHODS: Twenty-two severely obese patients with type 2
      diabetes underwent RYGB. A meal tolerance test (MTT) was performed 12 months
      after RYGB. The secretions of active glucagon-like peptide-1 (active GLP-1),
      glucose-dependent insulinotropic peptide (GIP), peptide YY, C-peptide and insulin
      during the MTT test were calculated using total area under the curve values
      (AUC). Remission was defined as glycated haemoglobin (A(1C)) of <6.5% and a
      fasting glucose concentration of <126 mg/dL for 1 year or more without active
      pharmacological therapy. RESULTS: Of the 22 patients, 16 (73%) had diabetes
      remission (remission group). The secretion CURVES of active GLP-1, GIP and
      peptide YY were not different between the groups. AUC of insulin and C-peptide
      were also not different. Homeostasis model assessment estimate of insulin
      resistance was significantly lower (1.26 +/- 1.05 versus 2.37 +/- 1.08, p =
      0.006), and Matsuda index of insulin sensitivity was significantly higher in the
      remission group (10.5 +/- 6.2 versus 5.8 +/- 2.1, p = 0.039). The disposition
      index (functional reserve of beta cells) was significantly higher in the
      remission group compared with that in the non-remission group (5.34 +/- 2.74
      versus 1.83 +/- 0.70, p < 0.001). CONCLUSIONS: Remission of diabetes after RYGB
      is not associated with a difference in gut hormone secretion. Patients remaining
      diabetic had higher insulin resistance and decreased beta cell functional
      reserve.

PMID- 22407972
TI  - Analysis of dose-response in flexible dose titration clinical studies.
AB  - Assessing dose-response from flexible-dose clinical trials (e.g., titration or
      dose escalation studies) is challenging and often problematic due to the
      selection bias caused by 'titration-to-response'. We investigate the performance
      of a dynamic linear mixed-effects (DLME) model and marginal structural model
      (MSM) in evaluating dose-response from flexible-dose titration clinical trials
      via simulations. The simulation results demonstrated that DLME models with
      previous exposure as a time-varying covariate may provide an unbiased and
      efficient estimator to recover exposure-response relationship from flexible-dose
      clinical trials. Although the MSM models with independent and exchangeable
      working correlations appeared to be able to recover the right direction of the
      dose-response relationship, it tended to over-correct selection bias and
      overestimated the underlying true dose-response. The MSM estimators were also
      associated with large variability in the parameter estimates. Therefore, DLME may
      be an appropriate modeling option in identifying dose-response when data from
      fixed-dose studies are absent or a fixed-dose design is unethical to be
      implemented.

PMID- 22407973
TI  - Biologics and molecular recognition: Mike Brigham-Burke memorial issue.

PMID- 22407974
TI  - Antigen-binding site anatomy and somatic mutations in antibodies that recognize
      different types of antigens.
AB  - The number of antibody structures co-crystallized with their respective antigens
      has increased rapidly in the last few years, thus offering a formidable source of
      information to gain insight into the structure-function relationships of this
      family of proteins. We have analyzed here 140 unique middle-resolution to high
      resolution (<3 A) antibody structures, including 55 in complex with proteins, 39
      with peptides, and 46 with haptens. We determined (i) length variations of the
      hypervariable loops, (ii) number of contacts with antigen, (iii) solvent
      accessible area buried upon binding, (iv) location and frequency of antigen
      contacting residues, (v) type of residues interacting with antigens, and (vi)
      putative somatic mutations. Except for somatic mutations, distinctive profiles
      were identified for all the variables analyzed. Compared with contacts, somatic
      mutations occurred with less abundance at any given position and extended beyond
      the regions in contact, with no clear difference among antibodies that recognize
      different types of antigens. This observation is consistent with the fact that
      although antigen recognition accomplished by shape and physicochemical
      complementarity is selective in nature, the somatic mutation process is
      stochastic and selection for mutations leading to improved affinity is not
      directly related to contact residues. Thus, the knowledge emerging from this
      study enhances our understanding of the structure-function relationship in
      antibodies while providing valuable guidance to design libraries for antibody
      discovery and optimization.

PMID- 22407975
TI  - Mapping of discontinuous conformational epitopes by amide hydrogen/deuterium
      exchange mass spectrometry and computational docking.
AB  - Understanding antigen-antibody interactions at the sub-molecular level is of
      particular interest for scientific, regulatory, and intellectual property
      reasons, especially with increasing demand for monoclonal antibody therapeutic
      agents. Although various techniques are available for the determination of an
      epitope, there is no widely applicable, high-resolution, and reliable method
      available. Here, a combination approach using amide hydrogen/deuterium exchange
      coupled with proteolysis and mass spectrometry (HDX-MS) and computational docking
      was applied to investigate antigen-antibody interactions. HDX-MS is a widely
      applicable, medium-resolution, medium-throughput technology that can be applied
      to epitope identification. First, the epitopes of cytochrome c-E8, IL-13-CNTO607,
      and IL-17A-CAT-2200 interactions identified using the HDX-MS method were compared
      with those identified by X-ray co-crystal structures. The identified epitopes are
      in good agreement with those identified using high-resolution X-ray
      crystallography. Second, the HDX-MS data were used as constraints for
      computational docking. More specifically, the non-epitope residues of an antigen
      identified using HDX-MS were designated as binding ineligible during
      computational docking. This approach, termed HDX-DOCK, gave more tightly
      clustered docking poses than stand-alone docking for all antigen-antibody
      interactions examined and improved docking results significantly for the
      cytochrome c-E8 interaction.

PMID- 22407976
TI  - Characterization of a high-affinity human antibody with a disulfide bridge in the
      third complementarity-determining region of the heavy chain.
AB  - Disulfide bridges are common in the antigen-binding site from sharks (new antigen
      receptor) and camels (single variable heavy-chain domain, VHH), in which they
      confer both structural diversity and domain stability. In human antibodies,
      cysteine residues in the third complementarity-determining region of the heavy
      chain (CDR-H3) are rare but naturally encoded in the IGHD germline genes. Here,
      by panning a phage display library designed based on human germline genes and
      synthetic CDR-H3 regions against a human cytokine, we identified an antibody (M3)
      containing two cysteine residues in the CDR-H3. It binds the cytokine with high
      affinity (0.4 nM), recognizes a unique epitope on the antigen, and has a distinct
      neutralization profile as compared with all other antibodies selected from the
      library. The two cysteine residues form a disulfide bridge as determined by mass
      spectrometric peptide mapping. Replacing the cysteines with alanines did not
      change the solubility and stability of the monoclonal antibody, but binding to
      the antigen was significantly impaired. Three-dimensional modeling and dynamic
      simulations were employed to explore how the disulfide bridge influences the
      conformation of CDR-H3 and binding to the antigen. On the basis of these results,
      we envision that designing human combinatorial antibody libraries to contain
      intra-CDR or inter-CDR disulfide bridges could lead to identification of human
      antibodies with unique binding profiles.

PMID- 22407977
TI  - Characterization of neutralizing affinity-matured human respiratory syncytial
      virus F binding antibodies in the sub-picomolar affinity range.
AB  - In the human adaptation and optimization of a mouse anti-human respiratory
      syncytial virus neutralizing antibody, affinity assessment was crucial to
      distinguish among potential candidates and to evaluate whether this correlated
      with function in vitro and in vivo. This affinity assessment was complicated by
      the trimeric nature of the antigen target, respiratory syncytial virus F (RSV-F)
      glycoprotein. In the initial affinity screen, surface plasmon resonance was used
      to determine the intrinsic binding affinities of anti-RSV-F Fab and
      immunoglobulin G (IgG) to the extracellular domain of RSV-F. This assessment
      required minimal biotinylation of the RSV-F protein and design of a capture
      strategy to minimize avidity effects. Approximately 30 Fabs were selected from
      three optimization phage display libraries on the basis of an initial ELISA
      screen. Surface plasmon resonance analysis demonstrated the success of
      optimization with some candidates from the screened libraries having low
      picomolar dissociation constants, more than 700-fold tighter than the parental
      monoclonal antibody (B21M). The affinities of these antibodies were further
      evaluated by a kinetic exclusion assay, a solution binding technology. One IgG
      (monoclonal antibody 029) displayed a low picomolar K(D) comparable with that of
      motavizumab, an RSV antibody in clinical study. Kinetic exclusion assay showed
      that two other of the matured IgGs (011 and 019) had sub-picomolar dissociation
      constants that could not be resolved further. We discuss the relevance of these
      interaction analysis results in the light of recently published data on the
      mechanism of F-driven viral fusion during paramyxoviral infection and 101F
      epitope conservation revealed from the recent crystal structure of RSV-F in the
      post-fusion state.

PMID- 22407978
TI  - Avidity confers FcgammaR binding and immune effector function to aglycosylated
      immunoglobulin G1.
AB  - Immunoglobulin G (IgG) antibodies are an integral part of the adaptive immune
      response that provide a direct link between humoral and cellular components of
      the immune system. Insights into relationships between the structure and function
      of human IgGs have prompted molecular engineering efforts to enhance or eliminate
      specific properties, such as Fc-mediated immune effector functions. Human IgGs
      have an N-glycosylation site at Asn297, located in the second heavy chain
      constant region (CH2). The composition of the Fc glycan can have substantial
      impacts on Fc gamma receptor(FcgammaR) binding. The removal of the glycan through
      enzymatic deglycosylation or mutagenesis of the N-linked glycosylation site has
      been reported to "silence" FcgammaR-binding and effector functions, particularly
      with assays that measure monomeric binding. However, interactions between IgGs
      and FcgammaRs are not limited to monomeric interactions but can be influenced by
      avidity, which takes into account the sum of multimeric interactions between
      antigen-engaged IgGs and FcgammaRs. We show here that under in vitro conditions,
      which allowed avidity binding, aglycosylated IgGs can bind to one of the
      FcgammaRs, FcgammaRI, and mediate effector functions. These studies highlight how
      the valency of a molecular interaction (monomeric binding versus avidity binding)
      can influence antibody/FcgammaR interactions such that avidity effects can
      translate very low intrinsic affinities into significant functional outcomes.

PMID- 22407979
TI  - The dimerization of glucagon-like peptide-2 MIMETIBODYTM is linked to leucine-17
      in the glucagon-like peptide-2 region.
AB  - Glucagon-like peptide-2 (GLP-2) is a member of the glucagon multigene family that
      is produced by intestinal enteroendocrine cells in response to food intake. GLP-2
      stimulates growth of the intestinal epithelium, enhances its barrier functions,
      and increases nutrient uptake. Therefore, a GLP-2 agonist may be efficacious in
      human diseases characterized by malabsorption or injury to the gastrointestinal
      epithelium. MIMETIBODYTM refers to a proprietary scaffold developed to extend the
      half-life of rapidly cleared peptides. It consists of a peptide linked to a
      scaffold that contains sequence elements from a human immunoglobulin G including
      those that allow recycling through the FcRn. The GLP-2 sequence was engineered
      into the MIMETIBODYTM scaffold. The primary state of both GLP-2 and the GLP-2
      MIMETIBODYTM in DPBS was a noncovalently associated dimer indicative of self
      interaction. The increased heterogeneity and the decreased lot-to-lot
      reproducibility caused by the self-interaction of therapeutic proteins are a
      challenge to drug development. A similar protein, GLP-1 MIMETIBODYTM, contains
      the related GLP-1 peptide and does not form a dimer under similar conditions.
      Therefore, to minimize or abrogate dimerization, several variants were made by
      substituting GLP-2 amino acids with the corresponding amino acids from GLP-1.
      Molecular weight and secondary structure analyses reveal that substituting
      leucine for glutamine at position 17 (L17Q) reduces dimerization and alpha-helix
      content yet retains bioactivity.

PMID- 22407980
TI  - Proximity energies: a framework for understanding concentrated solutions.
AB  - A high-concentration fluid may be defined as one in which the distance between
      the van der Waals surfaces of the molecules is on the same order of magnitude as
      the size of the molecules. Many biological fluids meet this definition of being
      concentrated. High concentration protein solutions are of commercial interest,
      too. In the biopharmaceutical industry, there is a desire to produce high
      concentration (>100 mg/ml) protein formulations. The goal of this paper is to
      provide an energetic framework for understanding the functional properties (e.g.,
      solubility, stability and viscosity) of high concentration solutions. Using this
      framework not only provides a simple, clear view of protein behavior at high
      concentrations, it also provides insights into how modifications to the protein
      or the solvent affect solution behavior. Thus, the paper provides a starting
      point for the rational manipulation of protein solubility, viscosity and
      stability.

PMID- 22407981
TI  - Probing the solution structure of tumor necrosis factor-alpha homotrimer and
      heterotrimer after complex perturbation using electrospray ionization mass
      spectrometry.
AB  - There are a number of proteins whose active forms are non-covalent multichain
      complexes. Therapeutic intervention involving such complexes has been proposed
      through the use of muteins to form heterostructures. These resulting structures
      would either not be recognized by receptors or would be inactive competitive
      inhibitors to wild-type (wt) proteins. We have used tumor necrosis factor-alpha
      (TNF-alpha) to establish that it is possible to use mass spectrometry to monitor
      the non-covalent solution structure of therapeutically relevant proteins and
      correlate the results with binding data. Mass spectrometry is shown to be able to
      directly monitor the state of the solution complexes to within 5 Da errors mass
      accuracy of theoretical mass at 50 kDa, as well as to resolve homocomplex from
      heterocomplex. Furthermore, it was determined that perturbation of the TNF-alpha
      complex, at or below pH 4.0, results in monomers that cannot reform into the
      multimeric complex, and the resulting protein solution can no longer bind to an
      anti-TNF-alpha antibody. Dissociation and re-association of the trimer was
      possible with the use of dimethyl sulfoxide at pH 5.5 and allowed for the
      resulting detection of both homotrimer and heterotrimer in solution with no
      impact on antibody binding. This work demonstrates that mass spectrometric
      techniques offer a means to monitor native solution interactions of non-covalent
      complexes and to differentiate multiple complexes from each other in solution.
      This method has applicability in the biopharmaceutical arena for monitoring
      engineering non-covalent drug complexes for the purpose of altering biological
      activity.

PMID- 22407982
TI  - Equilibrium and kinetic analysis of human interleukin-13 and IL-13 receptor alpha
      2 complex formation.
AB  - Interleukin 13 (IL-13) is a pleiotropic cytokine secreted by activated T cells.
      Both IL-13 and its polymorphic variant (IL-13-R110Q) have been shown to be
      associated with multiple diseases such as asthma and allergy. Two IL-13 receptors
      have been identified, IL-13R alpha-1 receptor (IL-13Ralpha1) and IL-13R alpha-2
      receptor (IL-13Ralpha2). It has been well established that IL-13 binds to IL
      13Ralpha1 alone with low nM affinity while binding to the IL-13Ralpha1/IL-4R
      receptor complex is significantly tighter (pM). The affinity between IL-13 and IL
      13Ralpha2, however, remains elusive. Several values have been reported in the
      literature varying from 20 pM to 2.5 nM. The affinities previously reported were
      obtained using surface plasmon resonance (SPR) or Scatchard analysis of (125) I
      IL-13 binding data. This report presents the results for the kinetics and
      equilibrium binding analysis studies performed using label-free kinetic exclusion
      assay (KEA) for the interaction of human IL-13 and IL-13Ralpha2. KEA equilibrium
      analysis showed that the affinities of IL-13Ralpha2 are 107 and 56 pM for IL-13
      and its variant (IL-13-R110Q), respectively. KEA kinetic analysis showed that a
      tight and very stable complex is formed between IL-13Ralpha2 and IL-13, as shown
      by calculated dissociation rate constants slower than 5 * 10(-5) per second.
      Kinetic analysis also showed significant differences in the kinetic behavior of
      wild type (wt) versus IL-13-R110Q. IL-13-R110Q not only associates to IL
      13Ralpha2 slower than wt human IL-13 (wt-IL-13), as previously reported, but IL
      13-R110Q also dissociates slower than wt-IL-13. These results show that IL
      13Ralpha2 is a high affinity receptor and provide a new perspective on kinetic
      behavior that could have significant implications in the understanding of the
      role of IL-13-R110Q in the disease state.

PMID- 22407984
TI  - Factors controlling the equilibrium of Pt-catalyzed [1,2]- versus [1,3]-acyloxy
      migration.
AB  - Pick a pathway: Upon activation with an electrophilic transition-metal catalyst,
      a propargylic acetate undergoes competing [1,2]- and [1,3]-acyloxy migration
      depending on the reaction temperature as well as the substituent pattern around
      the alkyne. The nature of the catalyst also affects the reaction course. The
      reactions provided clear evidence for the interconversion between carbenoid and
      allene intermediates (see scheme).

PMID- 22407985
TI  - Sensory and sympathetic correlates of heat pain sensitization and habituation in
      men and women.
AB  - BACKGROUND: Habituation and sensitization are important behavioural responses to
      repeated exposure to painful stimuli, but little is known about the factors
      determining sensory, affective and sympathetic habituation to repeated pain
      stimulation in men and women. METHODS: Thirty volunteers (15 women) underwent a
      standardized heat pain paradigm spread over 8 consecutive days. At the beginning
      of the experiment, personality dimensions, coping strategies and pain
      catastrophizing thoughts were determined. Receiving a series of 10 blocks of six
      painful heat stimuli a day, participants rated pain intensity and unpleasantness.
      Skin conductance was recorded throughout the sessions. RESULTS AND CONCLUSION:
      The results show similar habituation of both the sensory and affective dimensions
      of pain in men and women, although skin conductance did not undergo a significant
      decrease across the eight days. When focusing on single daily sessions, women
      showed pain sensitization but sympathetic habituation, while men showed pain
      sensitization but stable sympathetic activation. Our findings therefore indicate
      that the process of long-term habituation to painful heat stimuli is a common
      feature in both genders, whereas men and women might differently recruit their
      sympathetic nervous system for short-term pain processing. This study could
      potentially help to better evaluate gender-specific mechanisms in pain
      perception.

PMID- 22407986
TI  - Locoregional failure and the risk of distant metastasis after modern radiotherapy
      for head and neck cancer.
AB  - BACKGROUND: Evolving epidemiology and improvements in locoregional therapy
      necessitate reassessment of the relationship between locoregional failure and
      distant metastasis in squamous cell carcinoma of the head and neck (SCCHN).
      METHODS: Retrospective assessments of factors associated with distant metastasis
      free survival were made for 560 patients with SCCHN who received definitive
      radiotherapy (RT) +/- concurrent systemic therapy at our institution between 1995
      and 2007. RESULTS: Fifty-six patients (10.0%) developed distant metastasis. Three
      year actuarial locoregional control and distant metastasis-free survival were 72%
      and 87%, respectively. Multivariate analysis revealed N classification and
      locoregional failure as significant predictors of reduced distant metastasis-free
      survival (p < .001). In patients with distant metastasis detected after
      locoregional failure, the mean interval between these events was 11.6 months.
      CONCLUSION: Locoregional failure may play a causative role for distant metastasis
      in some patients with SCCHN, suggesting a need for continued focus on improving
      locoregional therapies.

PMID- 22407987
TI  - Abstracts of the Society of Hospital Medicine Annual Meeting. April 1-4, 2012.
      San Diego, California, USA.

PMID- 22407988
TI  - Methyl tert butyl ether is anti-angiogenic in both in vitro and in vivo mammalian
      model systems.
AB  - Methyl-tertiary butyl ether (MTBE), a well known gasoline oxygenate, and US Food
      and Drug Administration approved gallstone treatment, has been previously shown
      to specifically target teleost embryonic angiogenesis. The studies reported here
      were to determine whether similar vascular disrupting effects occur in higher
      vertebrate models. Rat brain endothelial cells were isolated and allowed to form
      microcapillary-like tubes on Matrigel. MTBE (0.34-34.0 mm) exposure resulted in a
      dose-dependent reduction of tube formation, with the LOAEL at 0.34 mm, while
      MTBE's primary metabolite, tertiary butyl alcohol had no effect on tube
      formation. HUVECs, a primary cell line representing macrovascular cells, were
      able to form tubes on Matrigel in the presence of MTBE (1.25-80 mm), but the
      tubes were narrower than those formed in the absence of MTBE. In a mouse Matrigel
      plug implantation assay, 34.0 mm MTBE completely inhibited vessel invasion into
      plugs containing endothelial cell growth supplement (ECGS) compared with control
      plugs with ECGS alone. When timed-pregnant Fisher 344 rats were gavaged with MTBE
      (500-1500 mg kg(-1) ) from day 6 of organogenesis through 10 days post
      parturition, no organ toxicity or histological changes in pup vasculature were
      observed. Results of the in vitro cell culture studies show that MTBE is anti
      angiogenic at mm concentrations and has potential use as an anti-angiogenic
      treatment for solid tumors with minimal toxicity.

PMID- 22407989
TI  - Enhanced light harvesting in plasmonic dye-sensitized solar cells by using a
      topologically ordered gold light-trapping layer.
AB  - Dye-sensitized solar cells (DSSCs) are promising low-cost, high-efficiency
      devices with low environmental impact. One of the important methods to improve
      their efficiencies involves increasing the light-harvesting efficiency. Earlier
      work has focused on varying the morphology of the photoanode. With such a
      hierarchical structured photoanode in hand, we modify herein the structure of the
      counter electrode to enhance the optical path length through the plasmonic and
      reflecttion effects. With the introduced topological gold layer, the photocurrent
      and efficiency are increased by 16 % and 18 %, respectively, due to the increased
      light collection. Besides, this effect is effective at both high and low levels
      of solar irradiation.

PMID- 22407990
TI  - Atherosclerotic inferior mesenteric artery stenosis resulting in large intestinal
      hypoperfusion: a paradigm shift in the diagnosis and management of symptomatic
      chronic mesenteric ischemia.
AB  - Symptomatic chronic mesenteric ischemia results from intestinal hypoperfusion and
      is classically thought to result from involvement of two or more mesenteric
      arteries. The celiac artery and superior mesenteric artery are most frequently
      implicated in this disease process, and their involvement usually results in
      symptoms of small intestinal ischemia. Symptomatic chronic mesenteric ischemia
      resulting predominantly from inferior mesenteric artery involvement has largely
      been overlooked but does gives rise to its own, unique clinical presentation with
      symptoms resulting from large intestinal ischemia. We present four patients with
      atherosclerotic inferior mesenteric artery stenosis with symptomatic chronic
      mesenteric ischemia that have unique clinical presentations consistent with large
      intestinal ischemia that resolved following percutaneous endovascular treatment
      of the inferior mesenteric artery stenosis. These cases represent a novel
      approach to the diagnosis and management of this disease process and may warrant
      a further subclassification of chronic mesenteric ischemia into chronic small
      intestinal ischemia and chronic large intestinal ischemia.

PMID- 22407991
TI  - Effective healing of diabetic skin wounds by using nonviral gene therapy based on
      minicircle vascular endothelial growth factor DNA and a cationic dendrimer.
AB  - BACKGROUND: The development of an efficient method to improve the wound healing
      process is urgently required for diabetic patients suffering a threat of limb
      amputations. Various growth factors have been proposed for treatment; however,
      more research still has to be carried out to maintain their curative effect. In
      the present study, we describe a simple nonviral gene therapy method for
      improving wound healing. METHODS: Minicircle plasmid DNA encoding vascular
      endothelial growth factor (VEGF) was combined with an arginine-grafted cationic
      dendrimer, PAM-RG4. The formed complexes were injected subcutaneously into the
      skin wounds of diabetic mice. RESULTS: Actively proliferating cells in wound
      tissue were efficiently transfected, resulting in a high level of VEGF
      expression. Within 6 days after injection, skin wounds in the diabetic mice were
      generally healed and displayed a well-ordered dermal structure, which was
      confirmed by histological staining. CONCLUSIONS: This simple and effective gene
      therapy method may represent a powerful tool for the treatment of diabetic foot
      ulcers and other diseases that are refractory to treatment.

PMID- 22407992
TI  - Hair testing for cocaine and metabolites by GC/MS: criteria to quantitatively
      assess cocaine use.
AB  - A simple, rapid and sensitive method has been developed and validated for the
      determination of cocaine and its main metabolites (benzoylecgonine and
      cocaethylene) in human hair. The method involved solid-phase extraction with an
      Oasis HLB extraction cartridge and subsequent analysis by GC/MS. The limit of
      detection was 0.01 ng mg(-1) for cocaine, 0.04 for benzoylecgonine and 0.03 for
      cocaethylene. The method validation included linearity (with a correlation
      coefficient >0.99 over the range 0.2-50 ng mg(-1) ), intra- and inter-day
      precision (always lower than 12%) and accuracy (mean relative error always below
      17%) to meet the bioanalytical acceptance criteria. The procedure was further
      applied to 40 hair samples from self-reported cocaine users arrested by the
      police who provided a positive urine-analysis for cocaine, and was demonstrated
      to be suitable for its application in forensic toxicology. New approaches were
      raised to detect false-negative results that allow a better interpretation of
      hair testing results.

PMID- 22407993
TI  - Clostridium difficile infection: the scope of the problem.
AB  - Clostridium difficile infection (CDI) is increasingly common, and it is
      associated with significant morbidity, mortality, and cost burden for patients
      and the healthcare system. The severity and rates of recurrent CDI and associated
      mortality are also increasing. This article is an overview of the changes in CDI
      epidemiology that have occurred since the turn of the century and the current
      scope of the problem. The 3 articles that follow in this supplement address the
      diagnosis and treatment of initial and recurrent CDI, and current practice
      guidelines for the prevention and control of CDI in the hospital setting.

PMID- 22407994
TI  - Meeting the challenge of recurrent Clostridium difficile infection.
AB  - Recurrent Clostridium difficile infection (CDI) is a growing problem that poses
      significant management challenges. There is no strong evidence to support a
      particular treatment strategy for recurrent CDI, especially those with multiple
      recurrences. However, a key strategy for reducing recurrent CDI is prompt
      diagnosis and treatment, facilitated by early recognition of patients at risk for
      recurrence.

PMID- 22407995
TI  - Strategies for prevention of Clostridium difficile infection.
AB  - Infection control is the most essential component of an effective overall
      management strategy for prevention of nosocomial Clostridium difficile infection
      (CDI). The cornerstones of CDI prevention are appropriate contact precautions and
      strict hand hygiene. Other important tactics are effective environmental
      cleaning, identification and removal of environmental sources of C. difficile,
      and antibiotic stewardship. Hospitalists, as coordinators of care for each
      patient and advocates for quality care, can spearhead these efforts.

PMID- 22407996
TI  - Current strategies for management of initial Clostridium difficile infection.
AB  - In the past decade, an epidemic strain of Clostridium difficile has led to
      increased incidence and severity of nosocomial C. difficile infections (CDI).
      Responsiveness to standard antimicrobial care for this strain is declining, and
      the morbidity and mortality of CDI and recurrent CDI are rising. Effective
      management requires a coordinated effort among all members of the healthcare team
      to facilitate early identification of patients at risk for CDI, early recognition
      of disease onset and confirmatory testing, prompt initiation of the most
      appropriate management approach, and ongoing monitoring throughout the continuum
      of care. Hospitalists, as coordinators of patient care, are in an ideal position
      to ensure that patients receive prompt and optimal treatment based on current
      clinical evidence and severity of the disease.

PMID- 22407997
TI  - Chemistry of energy conversion and storage.
AB  - Energy is a big issue in our society, fueled by growing awareness of the finite
      resources of liquid fossil fuels and the noticeable changes in our climate
      resulting from its consumption. The general consensus is that there should be a
      well-considered roadmap towards a future energy scenario, with the replacement of
      fossil energy by renewable energies as the final goal. This "Chemistry of Energy
      Conversion and Storage" issue contains papers dealing with the chemistry behind
      renewable energies.

PMID- 22407998
TI  - The mutual dependence between bone and gonads.
AB  - It has long been known that sex steroid hormones regulate bone mass accrual. This
      observation raises the testable hypothesis that bone may in turn regulate the
      synthesis and secretion of sex steroid hormones in one or both genders. This
      hypothesis is comprised within a more general hypothesis that bone mass, energy
      metabolism, and reproduction are regulated coordinately. The identification of
      osteocalcin as an osteoblast-specific secreted molecule allows us to address this
      question in molecular terms. This review details how the regulation of male
      fertility by osteocalcin was unraveled, and how osteocalcin signaling in Leydig
      cells of the testis occurs. It also discusses the implication of this novel mode
      of regulation of testosterone synthesis observed in males but not in females.

PMID- 22407999
TI  - Liposomal doxorubicin-based treatment in a preclinical model of adrenocortical
      carcinoma.
AB  - Adrenocortical carcinoma (ACC) is a rare endocrine tumor entity with poor
      prognosis. Medical treatment is limited to common cytotoxic agents, which are
      associated with low treatment responses. Thus, lack of therapeutic efficacy
      demands innovative treatment options for patients with advanced ACC. Recently, we
      have developed and characterized anti-IGF1 receptor (IGF1-R) immunoliposomes
      (SSLD-1H7) for the treatment of neuroendocrine tumors of the
      gastroenteropancreatic system. As previous results indicated putative
      applicability also for other IGF1-R-overexpressing tumor entities, we initiated
      testing of liposomal preparations in in vitro and in vivo models of ACC.
      Adrenocortical NCIh295 cells were used for in vitro association studies with
      different liposomal formulations. Thereby, flow cytometry revealed high cellular
      association and internalization of anti-IGF1-R immunoliposomes (soy
      phosphatidylcholine (SPC)/cholesterol (Chol)-polyethyleneglycol (PEG)-1H7, 50.1+/
      2.2%). Moreover, internalization of pegylated liposomes (SPC/Chol-PEG, 57.1+/
      2.4%) and an even higher uptake of plain liposomes (84.6+/-0.8%; P<0.0001) were
      detectable in adrenocortical tumor cells. In vivo, liposomal treatments were
      investigated on NCIh295 tumor xenografts in pharmacokinetic and therapeutic
      experiments. A significant reduction in tumor size was detectable in NCIh295
      tumor-bearing mice after a single treatment with SSLD-1H7 (0.89+/-0.15 cm;
      P=0.006) and a diminished efficacy for SSLD-PEG+ (1.01+/-0.19 cm; P=0.04) in
      comparison with untreated controls (1.5+/-0.0 cm). Thus, anti-IGF1-R
      immunoliposomes have been successfully tested in vitro and in vivo in a
      preclinical model for ACCs and could, therefore, represent a promising
      therapeutic approach for this tumor entity. Moreover, a combination of mitotane
      plus liposomally encapsulated cytostatic agents instead of free drugs could also
      be an interesting novel treatment option for ACC in the future.

PMID- 22408000
TI  - Parabens detection in different zones of the human breast: consideration of
      source and implications of findings.
AB  - This article is a discussion of the recent study by Barr, Metaxas, Harbach, Savoy
      and Darbre (2012; J. Appl. Toxicol. 32; doi: 10.1002/jat.1786) reporting residues
      of five paraben esters in the human breast, at concentrations up to the microgram
      per gram tissue range and with highest concentrations in the axilla area (closest
      to the underarm). The conclusion is that the detection of intact esters that have
      escaped the action of esterases is consistent with a local (dermal) exposure
      source since the metabolic capacity of the gut and liver would produce p
      hydroxybenzoic acid as the common metabolite. Whereas the zone concentration
      differences (propylparaben was found at highest concentrations in the axilla)
      support an underarm exposure model, seven subjects reportedly never used underarm
      cosmetics, and other exposure sources, including other cosmetic product types,
      are discussed. The findings are placed into context with the limited regulatory
      toxicology database on parabens, oestrogenic action of the parabens, and status
      of the parabens, cosmetics and human health debate.

PMID- 22408001
TI  - Ultraviolet light-irradiated photocrosslinkable chitosan hydrogel to prevent bone
      formation in both rat skull and fibula bone defects.
AB  - In the field of orthopaedic surgery, an orthopaedic surgeon sometimes requires to
      suppress excessive bone formation, such as ectopic bone formation, ossifying
      myositis and radio-ulnar synostosis, etc. Ultraviolet (UV) light irradiation of a
      photocrosslinkable chitosan (Az-CH-LA) generates an insoluble hydrogel within 30
      s. The purpose of this study was to evaluate the ability of the photocrosslinked
      chitosan hydrogel (PCH) to inhibit bone formation in an experimental model of
      bone defect. Rat calvarium and fibula were surgically injured and PCH was
      implanted into the resultant bone defects. The PCH implants significantly
      prevented bone formation in the bone defects during the 4 and 8 week observation
      periods. In the PCH-treated defects, fibrous tissues infiltrated by inflammatory
      cells were formed by day 7, completely filling the bone defects. In addition to
      these findings, expression of osteocalcin and runt-related gene 2 (RUNX2) mRNA,
      both markers of bone formation, was lower in the PCH-treated defects than in the
      controls. In contrast, collagen type 1alpha2 and alpha-smooth muscle actin (alpha
      SMA) mRNA levels were significantly higher in the PCH-treated defects after 1
      week. PCH stimulated the formation of fibrous tissue in bone defects while
      inhibiting bone formation. Thus, PCH might be a promising new therapeutic
      biomaterial for the prevention of bone formation in orthopaedic surgery.

PMID- 22408002
TI  - The male fight-flight response: a result of SRY regulation of catecholamines?
AB  - The SRY gene, which is located on the Y chromosome and directs male development,
      may promote aggression and other traditionally male behavioural traits, resulting
      in the fight-or-flight reaction to stress.

PMID- 22408003
TI  - Effect of chondroitin sulphate C on the in vitro and in vivo chondrogenesis of
      mesenchymal stem cells in crosslinked type II collagen scaffolds.
AB  - This study evaluates the crosslinkage effect of chondroitin sulphate C (CSC) and
      type II collagen (COL II) on chondrogenesis of mesenchymal stem cells (MSCs) in
      vitro and in vivo. In the in vitro studies, our results show that the weight
      ratio CSC:COL II that reaches 1.2:100 (CSC1.2/100 -COL II scaffold) can provide
      an optimal microenvironment for MSC chondrogenesis. When MSCs are cultured in
      this CSC1.2/100 -COL II scaffold, the chondrogenic gene expression of cultured
      cells is upregulated, while the osteogenic gene expression of these is
      downregulated. In addition, MSCs cultivated in the CSC1.2/100 -COL II scaffold
      are found to express the highest glycosaminoglycans:DNA ratio as compared to
      those in scaffolds of other CSC:COL II ratios. Histological and
      immunohistological evidence also supports the result. In the in vivo study, our
      results show that MSCs cultivated in the CSC1.2/100 -COL II scaffold demonstrate
      a better repair ability on cartilage lesions than does the COL II scaffold. After
      1 month in vivo, the injected MSCs in the CSC1.2/100 -COL II scaffold show lacuna
      structures and stimulate the formation of type II collagen at the defective
      sites. Six months after transplantation, the generated cells in the CSC1.2/100 
      COL II group show higher gene expressions of type II collagen and aggrecan but
      lower gene expression of type I collagen at the defective sites than those in the
      COL II group. The results strongly suggest that CSC1.2/100 -COL II scaffold can
      serve as a potential candidate for cartilage repair and improve the
      chondrogenesis of MSCs in general.

PMID- 22408004
TI  - An analysis of the use of multiple comparison corrections in ophthalmology
      research.
AB  - PURPOSE: The probability of type I error, or a false-positive result, increases
      as the number of statistical comparisons in a study increases. Statisticians have
      developed numerous corrections to account for the multiple comparison problem.
      This study discusses recent guidelines involving multiple comparison corrections,
      calculates the prevalence of corrections in ophthalmic research, and estimates
      the corresponding number of false-positive results reported at a recent
      international research meeting. METHODS: The 6415 abstracts presented at ARVO
      2010 were searched for statistical comparisons (P values) and for use of multiple
      comparison corrections. Studies that reported five or more P values while
      reporting no correction factor were used in a simulation study. The simulation
      study was conducted to estimate the number of false-positive results reported in
      these studies. RESULTS: Overall, 36% of abstracts reported P values and 1.2% of
      abstracts used some form of correction. Whereas 8% of abstracts reported at least
      five P values, only 5% of these used a multiple comparison correction. In these
      highly statistical studies, simulations resulted in 185 false-positive outcomes
      found in 30% of abstracts. CONCLUSIONS: The paucity of multiple comparison
      corrections in ophthalmic research results in inflated type I error and may
      produce unwarranted shifts in clinical or surgical care. Researchers must make a
      conscious effort to decide if and when to use a correction factor to ensure the
      validity of the data.

PMID- 22408005
TI  - Ephrin-a4 is involved in retinal neovascularization by regulating the VEGF
      signaling pathway.
AB  - PURPOSE: Retinal neovascularization (NV) is a major cause of blindness. Recent
      research suggests that factors other than VEGF participate in this process. This
      study aimed to determine the role of ephrin-A4 in retinal NV. METHODS: The
      expression and effect of ephrin-A4 was investigated in a mouse model of oxygen
      induced retinopathy (OIR) and the RF/6A retina endothelial cell line. Ephrin-A4
      expression and VEGF signaling pathway phosphorylation were determined by PCR,
      immunohistochemistry, and western blot analyses. ShRNA was used to silence ephrin
      A4 in vitro and in vivo. Retinal flat mounts and tube formation assays were
      performed to evaluate ephrin-A4 function in the NV process in vivo and in vitro.
      RESULTS: Ephrin-A4 was overexpressed in the retina of OIR mice and in RF/6A and
      RPE cells after CoCl2 stimulation. In vitro, Ephrin-A4/Fc treatment significantly
      increased the tube number of RF/6A cells on a membrane preparation and the
      phosphorylation levels of VEGR2, Akt1, and ERK1/2 in RF/6A cells. Moreover,
      ephrin-A4 knockout markedly suppressed pathologic neovascularization in vivo and
      inhibited the proliferation and tube formation capacity of RF/6A cells in vitro.
      Furthermore, in the absence of ephrin-A4, the phosphorylation of VEGFR2, Akt1,
      and ERK1/2 was defective under VEGF165 stimulation, and the proangiogenic
      function of VEGF165 was also compromised. CONCLUSIONS: This study suggests that
      ephrin-A4 plays an important role in retinal NV and is a potential target against
      retinal NV. The proangiogenic function of ephrin-A4 may be linked to its crucial
      role in the VEGF signaling pathway.

PMID- 22408007
TI  - Angiostatic effect of CXCR3 expressed on choroidal neovascularization.
AB  - PURPOSE: Several recent studies suggest that some chemokines/chemokine receptors
      are involved in choroidal neovascularization (CNV). CXCR3 was the focus of the
      present study because microarray analysis for murine laser-induced CNV model
      showed the increased expression of CXCR3. The purpose of this study was to
      evaluate the effect of CXCR3 on CNV. METHODS: Microarray analysis was performed
      for the mouse eyes with laser-induced CNV. CXCR3 expressions on the CNV were
      evaluated by immunohistochemistry and real-time RT-PCR. CNV was compared between
      CXCR3-deficient mice and wild-type mice, between mice treated with anti
      CXCR3/anti-IP-10 neutralizing antibody and mice treated with control IgG.
      Macrophage recruitment into CNV was also investigated. Ocular expressions of
      vascular endothelial growth factor (VEGF), pigment epithelium-derived factor
      (PEDF), C-C chemokine ligand-2 (CCL2), and complement component-3 (C3) were
      evaluated by real-time PCR. RESULTS: Microarray analysis and real-time RT-PCR
      revealed the elevation of CXCR3 and IP-10 in laser-treated mouse eyes compared
      with control eyes. Immunohistochemistry showed CXCR3 expression on the
      endothelial cells of CNV. Laser-induced CNV of CXCR3-deficient mice was
      significantly larger, with greater leakage in fluorescein angiography, and with
      greater macrophage-infiltration compared with wild-type mice (P < 0.01).
      Intravitreal injection of anti-CXCR3/anti-IP-10 neutralizing antibody exacerbated
      CNV. The CCL2 expression in the laser-treated eyes of CXCR3-deficient mice was
      higher than in those of wild-type mice (P < 0.05), whereas VEGF, PEDF, and C3
      showed no differences. CONCLUSIONS: These results suggested that CXCR3 expressed
      on CNV could have an angiostatic effect on it.

PMID- 22408006
TI  - Tyrosine-mutant AAV8 delivery of human MERTK provides long-term retinal
      preservation in RCS rats.
AB  - PURPOSE: The absence of Mertk in RCS rats results in defective RPE phagocytosis,
      accumulation of outer segment (OS) debris in the subretinal space, and subsequent
      death of photoreceptors. Previous research utilizing Mertk gene replacement
      therapy in RCS rats provided proof of concept for treatment of this form of
      recessive retinitis pigmentosa (RP); however, the beneficial effects on retinal
      function were transient. In the present study, we evaluated whether delivery of a
      MERTK transgene using a tyrosine-mutant AAV8 capsid could lead to more robust and
      longer-term therapeutic outcomes than previously reported. METHODS: An AAV8 Y733F
      vector expressing a human MERTK cDNA driven by a RPE-selective promoter was
      administrated subretinally at postnatal day 2. Functional and morphological
      analyses were performed at 4 months and 8 months post-treatment. Retinal
      vasculature and Muller cell activation were analyzed by quantifying acellular
      capillaries and glial fibrillary acidic protein immunostaining, respectively.
      RESULTS: Electroretinographic responses from treated eyes were more than one
      third of wild-type levels and OS were well preserved in the injection area even
      at 8 months. Rescue of RPE phagocytosis, prevention of retinal vasculature
      degeneration, and inhibition of Muller cell activation were demonstrated in the
      treated eyes for at least 8 months. CONCLUSIONS: This research describes a longer
      and much more robust functional and morphological rescue than previous studies.
      We also demonstrate for the first time that an AAV8 mutant capsid serotype vector
      has a substantial therapeutic potential for RPE-specific gene delivery. These
      results suggest that tyrosine-mutant AAV8 vectors hold promise for the treatment
      of individuals with MERTK-associated RP.

PMID- 22408008
TI  - Matrix metalloproteinase activity creates pro-angiogenic environment in primary
      human retinal pigment epithelial cells exposed to complement.
AB  - PURPOSE: Mechanistic studies have shown that inflammation, complement activation,
      extracellular matrix (ECM) turnover, growth factor imbalance, and oxidative
      stress are fundamental components of age-related macular degeneration (AMD).
      Matrix metalloproteinases (MMPs) mediate ECM turnover but also process various
      bioactive molecules. Here, we tested whether complement attack on RPE monolayers
      changes MMP secretion and activation, thereby altering the availability of growth
      factors in the extracellular space. METHODS: Human embryonic RPE monolayers with
      stable transepithelial resistance (TER) were established. Complement activation
      was induced with H2O2 and normal human serum. MMP-2/9, vascular endothelial
      growth factor (VEGF) and pigment epithelium-derived factor (PEDF) protein, and
      mRNA levels were analyzed by Western blotting, ELISA, and real-time PCR; activity
      of MMP-2/9 by gelatin zymography. RESULTS: Complement activation resulted in a
      loss of TER, which required transient membrane attack complex formation,
      activation of the alternative pathway, and VEGF secretion and signaling. Despite
      the generation of reactive oxygen species, cellular integrity or intracellular
      adenosine triphosphate (ATP) levels were unaffected. However, expression of MMP
      2/9 and their protease activity was elevated. Inhibition of MMP-2/9 activity
      increased PEDF and decreased VEGF levels in the apical and basal supernatants but
      had no effect on their expression levels. VEGF levels in the supernatant
      correlated with the level TER reduction. CONCLUSIONS: These studies suggest that
      complement activation, by altering the expression and activation of MMPs, has the
      ability to generate a proangiogenic environment by altering the balance between
      VEGF and PEDF. Our findings link reported results that have been associated with
      AMD pathogenesis; oxidative stress; complement activation; VEGF/PEDF ratio; and
      MMP activity.

PMID- 22408009
TI  - Genomic profiling reveals Pitx2 controls expression of mature extraocular muscle
      contraction-related genes.
AB  - PURPOSE: To assess the influence of the Pitx2 transcription factor on the global
      gene expression profile of extraocular muscle (EOM) of mice. METHODS: Mice with a
      conditional knockout of Pitx2, designated Pitx2(Deltaflox/Deltaflox) and their
      control littermates Pitx2(flox/flox), were used. RNA was isolated from EOM
      obtained at 3, 6, and 12 weeks of age and processed for microarray-based
      profiling. Pairwise comparisons were performed between mice of the same age and
      differentially expressed gene lists were generated. Select genes from the profile
      were validated using real-time quantitative polymerase chain reaction and protein
      immunoblot. Ultrastructural analysis was performed to evaluate EOM sarcomeric
      structure. RESULTS: The number of differentially expressed genes was relatively
      small. Eleven upregulated and 23 downregulated transcripts were identified common
      to all three age groups in the Pitx2-deficient extraocular muscle compared with
      littermate controls. These fell into a range of categories including muscle
      specific structural genes, transcription factors, and ion channels. The
      differentially expressed genes were primarily related to muscle contraction. We
      verified by protein and ultrastructural analysis that myomesin 2 was expressed in
      the Pitx2-deficient mice, and this was associated with development of M lines
      evident in their orbital region. CONCLUSIONS: The global transcript expression
      analysis uncovered that Pitx2 primarily regulates a relatively select number of
      genes associated with muscle contraction. Pitx2 loss led to the development of M
      line structures, a feature more typical of other skeletal muscle.

PMID- 22408010
TI  - Optic disc swelling in Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: This retrospective observational study was designed to evaluate the
      frequency of, and the factors associated with, optic disc swelling in Vogt
      Koyanagi-Harada disease (VKH). METHODS: A retrospective observational study was
      conducted. We analyzed 116 eyes of 58 patients with VKH. Demographic and clinical
      differences between patients with and without disc swelling were analyzed.
      RESULTS: Thirty-two eyes (27.6%) of 16 VKH patients had disc swelling. The mean
      age of the patients with disc swelling was higher than that of those without disc
      swelling (58.9 vs. 41.4, P = 0.0001). The disc-macula distance to disc diameter
      (DM/DD) ratio of the eyes with disc swelling was higher than that of those
      without disc swelling (2.81 vs. 2.59, P = 0.0007). The cup to disc (C/D) ratio of
      the eyes with disc swelling was smaller than that of those without disc swelling
      (0.18 vs. 0.32, P = 0.000001). The intraocular pressure was lower (P = 0.0084),
      and the refractive error was larger (P = 0.019), in eyes with disc swelling than
      in those without. There was no significant association between the presence of
      disc swelling and the range of retinal detachment, cerebrospinal fluid cell
      count, recurrence rate of VKH, or the incidence of sunset glow fundus. Among the
      eyes with disc swelling, 13 eyes of 7 patients had visual field defects even
      after the inflammation subsided, and these patients were older, had a higher
      DM/DD ratio, and had a smaller C/D ratio than those without visual field defects.
      CONCLUSIONS: The occurrence of disc swelling in VKH was significantly correlated
      with age and disc morphology, rather than the severity of inflammation. Some VKH
      patients with disc swelling develop visual field defects from optic disc
      involvement.

PMID- 22408011
TI  - Latent dry eye disease state variable.
AB  - PURPOSE: Evidence is growing that dry eye represents a common disease process
      resulting from a number of underlying pathologies that impact the ocular surface
      and that clinical estimates of dry eye severity reflect the magnitude of a single
      dry eye disease state variable, Theta. A theory for estimating Theta from scaled
      clinical observations is developed, and the hypothesis is tested that Theta
      exists. METHODS: The theory is developed around three assumptions: (1) a
      monotonic function unique to each person and indicator maps the indicator onto
      Theta, (2) between-person differences in mapping functions are random, and (3)
      observed indicator values include random perturbations. Data recently published
      by Sullivan and his colleagues were digitized from scatter plots of seven
      different indicators versus a composite severity score (square root of summed
      weighted squared indicator scores). RESULTS: The data were analyzed with a model
      derived under the specific assumptions that between-person variance in mapping
      functions is independent of the indicator value and random perturbations in
      observed indicator values are normally distributed. Tear osmolarity was the most
      sensitive indicator, and tear breakup time was the least. The distribution of
      residuals (squared difference between observed and predicted indicator values)
      agreed with model expectations for all indicators except tear osmolarity, which
      had larger residuals than expected, and the composite severity score, which had
      smaller residuals than expected. CONCLUSIONS: The results are consistent with the
      existence of a single latent dry eye disease state variable. Only tear osmolarity
      does not appear to map monotonically and/or unidimensionally onto the latent
      variable.

PMID- 22408012
TI  - Vector analysis of corneal and refractive astigmatism changes following toric
      pseudophakic and toric phakic IOL implantation.
AB  - PURPOSE: To determine the efficacy of the astigmatism correction following toric
      intraocular lens (IOL) and toric phakic IOL (pIOL) implantation in eyes with no
      previous ocular surgery and in postkeratoplasty (PKP) eyes. In addition, changes
      in corneal astigmatism were determined. METHODS: Astigmatism was analyzed in 35
      eyes with an AcrySof toric IOL, 35 eyes with an Artiflex toric pIOL, 50 eyes with
      an Artisan toric pIOL, and 40 PKP eyes with an Artisan toric pIOL. Refractive
      astigmatism was analyzed by using Alpins method. Surgically induced corneal
      astigmatism (SICA) was determined following a superior 2.2-mm, 3.4-mm, or 5.4-mm
      incision. Follow-up was 12 months. RESULTS: Following toric IOL implantation, the
      index of success was 0.14 and overall residual astigmatism, 0.37 diopter (D).
      Following toric pIOL implantation, the index of success was 0.32 (Artiflex) and
      0.18 (Artisan), and overall residual astigmatism was approximately 0.60 D. In PKP
      eyes, Artisan pIOLs resulted in an index of success of 0.28 and overall residual
      astigmatism of 1.56 D. The SICA, following 2.2-mm, 3.4-mm, 5.4-mm (normal eyes),
      and 5.4-mm (PKP eyes) incisions, was -0.25 +/- 0.42 D (P = 0.108), -0.31 +/- 0.43
      D (P < 0.001), -0.48 +/- 0.55 D (P < 0.001), and -0.49 +/- 1.48 D (P = 0.035),
      respectively. CONCLUSIONS: Toric IOLs and pIOLs provide an effective astigmatism
      correction. Incorporating the SICA into the toric IOL power calculation may
      further increase their effectiveness. Therefore, incorporation of 0 D, -0.30 D,
      or -0.50 D of SICA for a 2.2-, 3.4-, or 5.4-mm superior incision, respectively,
      is recommended.

PMID- 22408013
TI  - Induction of posterior capsule opacification by hyaluronic acid in an ex vivo
      model.
AB  - PURPOSE: Because hyaluronic acid (HA) is found in many surgical viscoelastic
      agents, this study aimed to determine (1) if HA receptors are present in the
      canine lens, (2) if the rate of lens epithelial cell (LEC) migration is altered
      following treatment with HA, and (3) if introduction of exogenous HA into the
      lens capsule promotes lenticular migration, thus contributing to posterior
      capsule opacification (PCO). METHODS: Normal and cataractous canine LECs were
      evaluated for expression of the HA receptor CD44 and the receptor for HA mediated
      motility (RHAMM) using immunohistochemistry, immunoblotting, and real-time PCR.
      Canine LEC were treated with various concentrations of HA, and induction of
      migration was monitored over time. Commercially available surgical viscoelastics
      were utilized ex vivo, and rates of PCO formation were analyzed. RESULTS: Basal
      protein and mRNA expression of both CD44 and RHAMM was noted. Cataractous canine
      LEC demonstrated significantly (P < 0.01) higher expression of CD44 but not
      RHAMM. Treatment with higher concentrations of HA resulted in a significant (P <
      0.01) increase in CD44 mRNA and increased LEC migration in vitro. Use of CD44
      neutralizing antibodies confirmed the role of CD44 in HA-induced lenticular
      migration. Viscoelastic material containing higher concentrations of HA led to
      increased rates of ex vivo PCO. CONCLUSIONS: Exogenous HA can induce lenticular
      migration and CD44 expression. Use of surgical viscoelastics that contained HA
      resulted in increased rates of ex vivo PCO suggesting that judicious selection
      and use of viscoelastic material during cataract surgery is warranted.

PMID- 22408014
TI  - Release of vancomycin and gentamicin from a contact lens versus a fibrin coating
      applied to a contact lens.
AB  - PURPOSE: To develop a contact lens capable of releasing antibiotics for a minimum
      of 8 hours for the treatment of bacterial keratitis. METHODS: Fibrin gel was
      loaded with vancomycin or gentamicin and then shaped into a curved disc. The disc
      was then used to coat the surface of a commercial contact lens or was sealed
      between two lenses. Separate contact lenses were soaked in solutions of
      vancomycin or gentamicin. The in vitro release kinetics for each system was
      determined using PBS at 37 degrees C and a particle-enhanced turbidimetric
      inhibition immunoassay. The bioactivity of the antibiotics released from the
      fibrin was confirmed by using a microbiological assay. RESULTS: Vancomycin and
      gentamicin were released at similar rates from soaked contact lenses and a
      coating of fibrin gel; however, the amounts of antibiotic delivered by the two
      systems differed considerably. The fibrin coating released over three times more
      gentamicin but less than one-fifth that of the lenses soaked in vancomycin. When
      fibrin was encapsulated between two contact lenses, significantly more controlled
      release was observed. For all systems, bactericidal amounts of vancomycin and
      gentamicin were released throughout the three-day testing period. CONCLUSIONS: As
      a delivery system, fibrin gel loaded with gentamicin performs better than contact
      lenses soaked in gentamicin. The opposite is true for vancomycin, where soaked
      lenses outperform fibrin gel. These systems could potentially be used as a
      treatment for bacterial keratitis.

PMID- 22408015
TI  - Innovation in biological microscopy: current status and future directions.
AB  - The current revolution in biological microscopy stems from the realisation that
      advances in optics and computational tools and automation make the modern
      microscope an instrument that can access all scales relevant to modern biology -
      from individual molecules all the way to whole tissues and organisms and from
      single snapshots to time-lapse recordings sampling from milliseconds to days. As
      these and more new technologies appear, the challenges of delivering them to the
      community grows as well. I discuss some of these challenges, and the examples
      where openly shared technology have made an impact on the field.

PMID- 22408016
TI  - Use of endogenous NADH fluorescence for real-time in situ visualization of
      epicardial radiofrequency ablation lesions and gaps.
AB  - Radiofrequency ablation (RFA) aims to produce lesions that interrupt reentrant
      circuits or block the spread of electrical activation from sites of abnormal
      activity. Today, there are limited means for real-time visualization of cardiac
      muscle tissue injury during RFA procedures. We hypothesized that the fluorescence
      of endogenous NADH could be used as a marker of cardiac muscle injury during
      epicardial RFA procedures. Studies were conducted in blood-free and blood
      perfused hearts from healthy adult Sprague-Dawley rats and New Zealand rabbits.
      Radiofrequency was applied to the epicardial surface of the heart using a 4-mm
      standard blazer ablation catheter. A dual camera optical mapping system was used
      to monitor NADH fluorescence upon ultraviolet illumination of the epicardial
      surface and to record optical action potentials using the voltage-sensitive probe
      RH237. Epicardial lesions were seen as areas of low NADH fluorescence. The
      lesions appeared immediately after ablation and remained stable for several
      hours. Real-time monitoring of NADH fluorescence allowed visualization of viable
      tissue between the RFA lesions. Dual recordings of NADH and epicardial electrical
      activity linked the gaps between lesions to postablation reentries. We found that
      the fluorescence of endogenous NADH aids the visualization of injured epicardial
      tissue caused by RFA. This was true for both blood-free and blood-perfused
      preparations. Gaps between NADH-negative regions revealed unablated tissue, which
      may promote postablation reentry or provide pathways for the conduction of
      abnormal electrical activity.

PMID- 22408017
TI  - Congenital heart disease and the specification of left-right asymmetry.
AB  - Complex congenital heart disease (CHD) is often seen in conjunction with
      heterotaxy, the randomization of left-right visceral organ situs. However, the
      link between cardiovascular morphogenesis and left-right patterning is not well
      understood. To elucidate the role of left-right patterning in cardiovascular
      development, we examined situs anomalies and CHD in mice with a loss of function
      allele of Dnaic1, a dynein protein required for motile cilia function and left
      right patterning. Dnaic1 mutants were found to have nodal cilia required for left
      right patterning, but they were immotile. Half the mutants had concordant organ
      situs comprising situs solitus or mirror symmetric situs inversus. The remaining
      half had randomized organ situs or heterotaxy. Looping of the heart tube, the
      first anatomical lateralization, showed abnormal L-loop bias rather than the
      expected D-loop orientation in heterotaxy and nonheterotaxy mutants. Situs
      solitus/inversus mutants were viable with mild or no defects consisting of azygos
      continuation and/or ventricular septal defects, whereas all heterotaxy mutants
      had complex CHD. In heterotaxy mutants, but not situs solitus/inversus mutants,
      the morphological left ventricle was thin and often associated with a hypoplastic
      transverse aortic arch. Thus, in conclusion, Dnaic1 mutants can achieve situs
      solitus or inversus even with immotile nodal cilia. However, the finding of
      abnormal L-loop bias in heterotaxy and nonheterotaxy mutants would suggest motile
      cilia are required for normal heart looping. Based on these findings, we propose
      motile nodal cilia patterns heart looping but heart and visceral organ
      lateralization is driven by signaling not requiring nodal cilia motility.

PMID- 22408018
TI  - Sympathetic neural responses to 24-hour sleep deprivation in humans: sex
      differences.
AB  - Sleep deprivation has been linked to hypertension, and recent evidence suggests
      that associations between short sleep duration and hypertension are stronger in
      women. In the present study we hypothesized that 24 h of total sleep deprivation
      (TSD) would elicit an augmented pressor and sympathetic neural response in women
      compared with men. Resting heart rate (HR), blood pressure (BP), and muscle
      sympathetic nerve activity (MSNA) were measured in 30 healthy subjects (age, 22
      +/- 1; 15 men and 15 women). Relations between spontaneous fluctuations of
      diastolic arterial pressure and MSNA were used to assess sympathetic baroreflex
      function. Subjects were studied twice, once after normal sleep and once after TSD
      (randomized, crossover design). TSD elicited similar increases in systolic,
      diastolic, and mean BP in men and women (time, P < 0.05; time * sex, P > 0.05).
      TSD reduced MSNA in men (25 +/- 2 to 16 +/- 3 bursts/100 heart beats; P = 0.02),
      but not women. TSD did not alter spontaneous sympathetic or cardiovagal
      baroreflex sensitivities in either sex. However, TSD shifted the spontaneous
      sympathetic baroreflex operating point downward and rightward in men only. TSD
      reduced testosterone in men, and these changes were correlated to changes in
      resting MSNA (r = 0.59; P = 0.04). Resting HR, respiratory rate, and estradiol
      were not altered by TSD in either sex. In conclusion, TSD-induced hypertension
      occurs in both sexes, but only men demonstrate altered resting MSNA. The sex
      differences in MSNA are associated with sex differences in sympathetic baroreflex
      function (i.e., operating point) and testosterone. These findings may help
      explain why associations between sleep deprivation and hypertension appear to be
      sex dependent.

PMID- 22408019
TI  - Two weeks of muscle immobilization impairs functional sympatholysis but increases
      exercise hyperemia and the vasodilatory responsiveness to infused ATP.
AB  - During exercise, contracting muscles can override sympathetic vasoconstrictor
      activity (functional sympatholysis). ATP and adenosine have been proposed to play
      a role in skeletal muscle blood flow regulation. However, little is known about
      the role of muscle training status on functional sympatholysis and ATP- and
      adenosine-induced vasodilation. Eight male subjects (22 +/- 2 yr, Vo(2max): 49 +/
      2 ml O(2).min(-1).kg(-1)) were studied before and after 5 wk of one-legged knee
      extensor training (3-4 times/wk) and 2 wk of immobilization of the other leg. Leg
      hemodynamics were measured at rest, during exercise (24 +/- 4 watts), and during
      arterial ATP (0.94 +/- 0.03 MUmol/min) and adenosine (5.61 +/- 0.03 MUmol/min)
      infusion with and without coinfusion of tyramine (11.11 MUmol/min). During
      exercise, leg blood flow (LBF) was lower in the trained leg (2.5 +/- 0.1 l/min)
      compared with the control leg (2.6 +/- 0.2 l/min; P < 0.05), and it was higher in
      the immobilized leg (2.9 +/- 0.2 l/min; P < 0.05). Tyramine infusion lowers LBF
      similarly at rest, but, when tyramine was infused during exercise, LBF was
      blunted in the immobilized leg (2.5 +/- 0.2 l/min; P < 0.05), whereas it was
      unchanged in the control and trained leg. Mean arterial pressure was lower during
      exercise with the trained leg compared with the immobilized leg (P < 0.05), and
      leg vascular conductance was similar. During ATP infusion, the LBF response was
      higher after immobilization (3.9 +/- 0.3 and 4.5 +/- 0.6 l/min in the control and
      immobilized leg, respectively; P < 0.05), whereas it did not change after
      training. When tyramine was coinfused with ATP, LBF was reduced in the
      immobilized leg (P < 0.05) but remained similar in the control and trained leg.
      Training increased skeletal muscle P2Y2 receptor content (P < 0.05), whereas it
      did not change with immobilization. These results suggest that muscle inactivity
      impairs functional sympatholysis and that the magnitude of hyperemia and blood
      pressure response to exercise is dependent on the training status of the muscle.
      Immobilization also increases the vasodilatory response to infused ATP.

PMID- 22408020
TI  - Cardiac hypertrophy in the newborn delays the maturation of fatty acid beta
      oxidation and compromises postischemic functional recovery.
AB  - During the neonatal period, cardiac energy metabolism progresses from a fetal
      glycolytic profile towards one more dependent on mitochondrial oxidative
      metabolism. In this study, we identified the effects of cardiac hypertrophy on
      neonatal cardiac metabolic maturation and its impact on neonatal postischemic
      functional recovery. Seven-day-old rabbits were subjected to either a sham or a
      surgical procedure to induce a left-to-right shunt via an aortocaval fistula to
      cause RV volume-overload. At 3 wk of age, hearts were isolated from both groups
      and perfused as isolated, biventricular preparations to assess cardiac energy
      metabolism. Volume-overload resulted in cardiac hypertrophy (16% increase in
      cardiac mass, P < 0.05) without evidence of cardiac dysfunction in vivo or in
      vitro. Fatty acid oxidation rates were 60% lower (P < 0.05) in hypertrophied
      hearts than controls, whereas glycolysis increased 246% (P < 0.05). In contrast,
      glucose and lactate oxidation rates were unchanged. Overall ATP production rates
      were significantly lower in hypertrophied hearts, resulting in increased AMP-to
      ATP ratios in both aerobic hearts and ischemia-reperfused hearts. The lowered
      energy generation of hypertrophied hearts depressed functional recovery from
      ischemia. Decreased fatty acid oxidation rates were accompanied by increased
      malonyl-CoA levels due to decreased malonyl-CoA decarboxylase
      activity/expression. Increased glycolysis in hypertrophied hearts was accompanied
      by a significant increase in hypoxia-inducible factor-1alpha expression, a key
      transcriptional regulator of glycolysis. Cardiac hypertrophy in the neonatal
      heart results in a reemergence of the fetal metabolic profile, which compromises
      ATP production in the rapidly maturing heart and impairs recovery of function
      following ischemia.

PMID- 22408021
TI  - Differential effects of high-fat diet on myocardial lipid metabolism in failing
      and nonfailing hearts with angiotensin II-mediated cardiac remodeling in mice.
AB  - Normal myocardium adapts to increase of nutritional fatty acid supply by
      upregulation of regulatory proteins of the fatty acid oxidation pathway. Because
      advanced heart failure is associated with reduction of regulatory proteins of
      fatty acid oxidation, we hypothesized that failing myocardium may not be able to
      adapt to increased fatty acid intake and therefore undergo lipid accumulation,
      potentially aggravating myocardial dysfunction. We determined the effect of high
      fat diet in transgenic mice with overexpression of angiotensinogen in the
      myocardium (TG1306/R1). TG1306/R1 mice develop ANG II-mediated left ventricular
      hypertrophy, and at one year of age approximately half of the mice present heart
      failure associated with reduced expression of regulatory proteins of fatty acid
      oxidation and reduced palmitate oxidation during ex vivo working heart perfusion.
      Hypertrophied hearts from TG1306/R1 mice without heart failure adapted to high
      fat feeding, similarly to hearts from wild-type mice, with upregulation of
      regulatory proteins of fatty acid oxidation and enhancement of palmitate
      oxidation. There was no myocardial lipid accumulation or contractile dysfunction.
      In contrast, hearts from TG1306/R1 mice presenting heart failure were unable to
      respond to high-fat feeding by upregulation of fatty acid oxidation proteins and
      enhancement of palmitate oxidation. This resulted in accumulation of
      triglycerides and ceramide in the myocardium, and aggravation of contractile
      dysfunction. In conclusion, hearts with ANG II-induced contractile failure have
      lost the ability to enhance fatty acid oxidation in response to increased fatty
      acid supply. The ensuing accumulation of lipid compounds may play a role in the
      observed aggravation of contractile dysfunction.

PMID- 22408022
TI  - Diet-induced obesity severely impairs myelinated aortic baroreceptor reflex
      responses.
AB  - Diet-induced obesity (DIO) attenuates the arterial cardiac baroreceptor reflex,
      but the mechanisms and sites of action are unknown. This study tested the
      hypothesis that DIO impairs central aortic baroreceptor pathways. Normal chow
      control (CON) and high-fat-chow obesity-resistant (OR) and obesity-prone (OP)
      rats were anesthetized (inactin, 120 mg/kg) and underwent sinoaortic denervation.
      The central end of the aortic depressor nerve (ADN) was electrically stimulated
      to generate frequency-dependent baroreflex curves (5-100 Hz) during selective
      activation of myelinated (A-fiber) or combined (A- and C-fiber) ADN
      baroreceptors. A mild stimulus (1 V) that activates only A-fiber ADN
      baroreceptors induced robust, frequency-dependent depressor and bradycardic
      responses in CON and OR rats, but these responses were completely abolished in OP
      rats. Maximal activation of A fibers (3 V) elicited frequency-dependent reflexes
      in all groups, but a dramatic deficit was still present in OP rats. Activation of
      all ADN baroreceptors (20 V) evoked even larger reflex responses. Depressor
      responses were nearly identical among groups, but OP rats still exhibited
      attenuated bradycardia. In separate groups of rats, the reduced heart rate (HR)
      response to maximal activation of ADN A fibers (3 V) persisted in OP rats
      following pharmacological blockade of beta(1)-adrenergic or muscarinic receptors,
      suggesting deficits in both parasympathetic nervous system (PNS) and sympathetic
      nervous system (SNS) reflex pathways. However, the bradycardic responses to
      direct efferent vagal stimulation were similar among groups. Taken together, our
      data suggest that DIO severely impairs the central processing of myelinated
      aortic baroreceptor control of HR, including both PNS and SNS components.

PMID- 22408023
TI  - Theoretical comparison of wall-derived and erythrocyte-derived mechanisms for
      metabolic flow regulation in heterogeneous microvascular networks.
AB  - The objective of this study is to compare the effectiveness of metabolic signals
      derived from erythrocytes and derived from the vessel wall for regulating blood
      flow in heterogeneous microvascular networks. A theoretical model is used to
      simulate blood flow, mass transport, and vascular responses. The model accounts
      for myogenic, shear-dependent, and metabolic flow regulation. Metabolic signals
      are assumed to be propagated upstream along vessel walls via a conducted
      response. Arteriolar tone is assumed to depend on the conducted metabolic signal
      as well as local wall shear stress and wall tension, and arteriolar diameters are
      calculated based on vascular smooth muscle mechanics. The model shows that under
      certain conditions metabolic regulation based on wall-derived signals can be more
      effective in matching perfusion to local oxygen demand relative to regulation
      based on erythrocyte-derived signals, resulting in higher extraction and lower
      oxygen deficit. The lower effectiveness of the erythrocyte-derived signal is
      shown to result in part from the unequal partition of hematocrit at diverging
      bifurcations, such that low-flow vessels tend to receive a reduced hematocrit and
      thereby experience a reduced erythrocyte-derived metabolic signal. The model
      simulations predict that metabolic signals independent of erythrocytes may play
      an important role in local metabolic regulation of vascular tone and flow
      distribution in heterogeneous microvessel networks.

PMID- 22408024
TI  - Slackness between vessel and myocardium is necessary for coronary flow reserve.
AB  - Tone regulation in coronary microvessels has largely been studied in isolated
      vessels in the absence of myocardial tethering. Here, the potential effect of
      radial tethering and interstitial space connective tissue (ISCT) between coronary
      microvessels and the surrounding myocardium was studied. We hypothesized that
      rigid tethering between microvessels and the myocardium would constrain the
      active contraction of arterioles and is not compatible with the observed tone
      regulation. The ISCT between coronary microvessels and myocardium in five swine
      was found to increase exponentially from 0.22 +/- 0.02 MUm in capillaries
      (modified Strahler order 0) of the endocardium to 34.9 +/- 7.1 MUm in epicardial
      vessels (order 10). Microvessels with both soft tethering and ISCT gap were
      capable of significant changes in vessel resistance (up to an ~1,600% increase),
      consistent with experimental measurements of high coronary flow reserve.
      Additionally, the mechanical energy required for myogenic contraction was
      estimated. The results indicate that rigid tethering requires up to four times
      more mechanical energy than soft tethering in the absence of a gap. Hence, the
      experimental measurements and model predictions suggest that effectiveness and
      efficiency in tone regulation can be achieved only if the vessel is both softly
      tethered to and separated from the myocardium in accordance with the experimental
      findings of ISCT gap. These results have fundamental implications on future
      simulations of coronary circulation.

PMID- 22408025
TI  - Transcription factor CHF1/Hey2 regulates EC coupling and heart failure in mice
      through regulation of FKBP12.6.
AB  - Heart failure is a leading cause of morbidity and mortality in Western society.
      The cardiovascular transcription factor CHF1/Hey2 has been linked to experimental
      heart failure in mice, but the mechanisms by which it regulates myocardial
      function remain incompletely understood. The objective of this study was to
      determine how CHF1/Hey2 affects development of heart failure through examination
      of contractility in a myocardial knockout mouse model. We generated myocardial
      specific knockout mice. At baseline, cardiac function was normal, but, after
      aortic banding, the conditional knockout mice demonstrated a greater increase in
      ventricular weight-to-body weight ratio compared with control mice (5.526 vs.
      4.664 mg/g) and a significantly decreased ejection fraction (47.8 vs. 72.0%
      control). Isolated cardiac myocytes from these mice showed decreased calcium
      transients and fractional shortening after electrical stimulation. To determine
      the molecular basis for these alterations in excitation-contraction coupling, we
      first measured total sarcoplasmic reticulum calcium stores and calcium-dependent
      force generation in isolated muscle fibers, which were normal, suggesting a
      defect in calcium cycling. Analysis of gene expression demonstrated normal
      expression of most genes known to be involved in myocardial calcium cycling, with
      the exception of the ryanodine receptor binding protein FKBP12.6, which was
      expressed at increased levels in the conditional knockout hearts. Treatment of
      the isolated knockout myocytes with FK506, which inhibits the association of
      FKBP12.6 with the ryanodine receptor, restored contractile function. These
      findings demonstrate that conditional deletion of CHF1/Hey2 in the myocardium
      leads to abnormalities in calcium handling mediated by FKBP12.6 that predispose
      to pressure overload-induced heart failure.

PMID- 22408026
TI  - Ras dexamethasone-induced protein 1 is a modulator of hormone secretion in the
      volume overloaded heart.
AB  - Because of the crucial role of the endocrine heart in maintaining homeostasis,
      considerable effort has been focused on the elucidation of the mechanistic
      underlying gene expression and secretion of the cardiac hormones atrial
      natriuretic factor (ANF) and brain natriuretic peptide (BNP). However, much
      remains to be determined regarding specific molecular events involved in
      cardiocyte secretory function. In this work, we identified genes involved in the
      transcriptional response of the endocrine heart to volume overload (VO) and
      signaling pathways involved in its regulation. To this end, the cardiac atrial
      and ventricular transcriptomes were analyzed in the heart of rats subjected to
      experimentally induced aorto-caval shunt VO. Pathway analysis revealed unique
      gene expression profiles in the VO atria for G-protein signaling, notably a
      significant downregulation of Ras dexamethasone-induced protein 1 (RASD1). In
      vitro, knockdown of RASD1 in the atrial-derived HL-1 cells, significantly
      increased ANF secretion. Concurrent knockdown of RASD1 and its effectors
      Galpha(o1) or Gbeta(1)gamma(2) abrogated the endocrine response, demonstrating a
      previously unknown negative modulator role for RASD1. RASD1 thus emerges as a
      tonic inhibitor of ANF secretion and illustrates for the first time the concept
      of inhibitory protein regulators of ANF release. The novel molecular function
      identified herein for RASD1 is of considerable importance given its therapeutic
      implications for cardiovascular disease.

PMID- 22408027
TI  - Specific inhibition of mitochondrial oxidative stress suppresses inflammation and
      improves cardiac function in a rat pneumonia-related sepsis model.
AB  - Using a mitochondria-targeted vitamin E (Mito-Vit-E) in a rat pneumonia-related
      sepsis model, we examined the role of mitochondrial reactive oxygen species in
      sepsis-mediated myocardial inflammation and subsequent cardiac contractile
      dysfunction. Sepsis was produced in adult male Sprague-Dawley rats via
      intratracheal injection of S. pneumonia (4 * 10(6) colony formation units per
      rat). A single dose of Mito-Vit-E, vitamin E, or control vehicle, at 21.5
      MUmol/kg, was administered 30 min postinoculation. Blood was collected, and heart
      tissue was harvested at various time points. Mito-Vit-E in vivo distribution was
      confirmed by mass spectrometry. In cardiac mitochondria, Mito-Vit-E improved
      total antioxidant capacity and suppressed H(2)O(2) generation, whereas vitamin E
      offered little effect. In cytosol, both antioxidants decreased H(2)O(2) levels,
      but only vitamin E strengthened antioxidant capacity. Mito-Vit-E protected
      mitochondrial structure and function in the heart during sepsis, demonstrated by
      reduction in lipid and protein oxidation, preservation of mitochondrial membrane
      integrity, and recovery of respiratory function. While both Mito-Vit-E and
      vitamin E suppressed sepsis-induced peripheral and myocardial production of
      proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, and
      interleukin-6), Mito-Vit-E exhibited significantly higher efficacy (P < 0.05).
      Stronger anti-inflammatory action of Mito-Vit-E was further shown by its near
      complete inhibition of sepsis-induced myeloperoxidase accumulation in myocardium,
      suggesting its effect on neutrophil infiltration. Echocardiography analysis
      indicated that Mito-Vit-E ameliorated cardiac contractility of sepsis animals,
      shown by improved fractional shortening and ejection fraction. Together, our data
      suggest that targeted scavenging of mitochondrial reactive oxygen species
      protects mitochondrial function, attenuates tissue-level inflammation, and
      improves whole organ activities in the heart during sepsis.

PMID- 22408028
TI  - O-GlcNAc signaling is essential for NFAT-mediated transcriptional reprogramming
      during cardiomyocyte hypertrophy.
AB  - The regulation of cardiomyocyte hypertrophy is a complex interplay among many
      known and unknown processes. One specific pathway involves the phosphatase
      calcineurin, which regulates nuclear translocation of the essential cardiac
      hypertrophy transcription factor, nuclear factor of activated T-cells (NFAT).
      Although metabolic dysregulation is frequently described during cardiac
      hypertrophy, limited insights exist regarding various accessory pathways. One
      metabolically derived signal, beta-O-linked N-acetylglucosamine (O-GlcNAc), has
      emerged as a highly dynamic posttranslational modification of serine and
      threonine residues regulating physiological and stress processes. Given the
      metabolic dysregulation during hypertrophy, we hypothesized that NFAT activation
      is dependent on O-GlcNAc signaling. Pressure overload-induced hypertrophy (via
      transverse aortic constriction) in mice or treatment of neonatal rat cardiac
      myocytes with phenylephrine significantly enhanced global O-GlcNAc signaling.
      NFAT-luciferase reporter activity revealed O-GlcNAc-dependent NFAT activation
      during hypertrophy. Reversal of enhanced O-GlcNAc signaling blunted cardiomyocyte
      NFAT-induced changes during hypertrophy. Taken together, these results
      demonstrate a critical role of O-GlcNAc signaling in NFAT activation during
      hypertrophy and provide evidence that O-GlcNAc signaling is coordinated with the
      onset and progression of cardiac hypertrophy. This represents a potentially
      significant and novel mechanism of cardiac hypertrophy, which may be of
      particular interest in future in vivo studies of hypertrophy.

PMID- 22408029
TI  - Advances in genetics show the need for extending screening strategies for
      autosomal dominant hypercholesterolaemia.
AB  - Aims Autosomal dominant hypercholesterolaemia (ADH) is a major risk factor for
      coronary artery disease. This disorder is caused by mutations in the genes coding
      for the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and
      proprotein convertase subtilisin/kexin 9 (PCSK9). However, in 41% of the cases,
      we cannot find mutations in these genes. In this study, new genetic approaches
      were used for the identification and validation of new variants that cause ADH. 
      Methods and results Using exome sequencing, we unexpectedly identified a novel
      APOB mutation, p.R3059C, in a small-sized ADH family. Since this mutation was
      located outside the regularly screened APOB region, we extended our routine
      sequencing strategy and identified another novel APOB mutation (p.K3394N) in a
      second family. In vitro analyses show that both mutations attenuate binding to
      the LDLR significantly. Despite this, both mutations were not always associated
      with ADH in both families, which prompted us to validate causality through using
      a novel genetic approach.  Conclusion This study shows that advances in genetics
      help increasing our understanding of the causes of ADH. We identified two novel
      functional APOB mutations located outside the routinely analysed APOB region,
      suggesting that screening for mutations causing ADH should encompass the entire
      APOB coding sequence involved in LDL binding to help identifying and treating
      patients at increased cardiovascular risk.

PMID- 22408030
TI  - Should we SHIFT our thinking about digoxin? Observations on ivabradine and heart
      rate reduction in heart failure.
AB  - AIMS: The importance of heart rate in the pathophysiology of heart failure with
      reduced LVEF has recently attracted attention. In particular, the findings of the
      Systolic Heart failure treatment with the I(f) inhibitor ivabradine Trial (SHIFT)
      have put special emphasis on heart rate reduction with ivabradine for improvement
      in clinical outcomes. Of course, there is a much older drug that reduces heart
      rate, i.e. digoxin. METHODS AND RESULTS: In this short commentary, we
      retrospectively analyse the Digitalis Investigation Group (DIG) Trial looking at
      the primary composite endpoint used in SHIFT (i.e. cardiovascular death or
      hospital admission for worsening heart failure) and compare the effect of digoxin
      on this endpoint with that of ivabradine. A remarkably similar risk reduction in
      the composite outcome and in its components appears evident among patients
      receiving the active treatment in both studies (although ivabradine was added to
      a beta-blocker, whereas digoxin was not). CONCLUSIONS: This raises the question
      of whether the Cardiological community dismissed digoxin too readily and if we
      should reappraise its potential role in the treatment of heart failure.

PMID- 22408031
TI  - Clinical experience of entirely subcutaneous implantable cardioverter
      defibrillators in children and adults: cause for caution.
AB  - AIMS: This paper describes our clinical experience of using an entirely
      subcutaneous implantable cardioverter-defibrillator (S-ICD) in children and
      adults. Maintaining lead integrity and long-term vascular access are critical
      challenges of ICD therapy, especially in younger patients. The S-ICD has
      considerable theoretical advantages in selected patients without pacing
      indications, particularly children and young adults. Although sensing in an S-ICD
      may be influenced by age, pathology, and posture, there are currently few
      published data on clinical sensing performance outside the setting of intra
      operative testing or in younger patients. METHODS AND RESULTS: Patients were
      selected by a multi-disciplinary team on clinical grounds for S-ICD implantation
      from a broad population at risk of sudden arrhythmic death. Sixteen patients
      underwent implantation [median age 20 years (range 10-48 years)]. Twelve had
      primary electrical disease and four had congenital structural heart disease.
      There were no operative complications, and ventricular fibrillation (VF)
      induction testing was successful in all cases. During median follow-up of 9
      months (range 3-15 months), three children required re-operation. Eighteen
      clinical shocks were delivered in six patients. Ten shocks in four patients were
      inappropriate due to T-wave over-sensing. Within the eight shocks for ventricular
      arrhythmia, three were delivered for VF, among which two had delays in detection
      with time to therapy of 24 and 27 s. CONCLUSION: The S-ICD is an important new
      option for some patients. However, these data give cause for caution in light of
      the limited published data regarding clinical sensing capabilities, particularly
      among younger patients.

PMID- 22408032
TI  - The beat goes on: on the importance of heart rate in chronic heart failure.

PMID- 22408033
TI  - Cancer in cardiovascular drug trials and vice versa: a personal perspective.

PMID- 22408034
TI  - Effects of celecoxib on restenosis after coronary intervention and evolution of
      atherosclerosis (Mini-COREA) trial: celecoxib, a double-edged sword for patients
      with angina.
AB  - AIMS: In the previous COREA-TAXUS trial, a 6-month adjunctive use of celecoxib
      reduced target-lesion revascularization (TLR) without increased thrombotic risk.
      We aimed to confirm the effects of 3-month celecoxib in patients receiving drug
      eluting stent (DES) implantation in the larger prospective, randomized trial.
      METHODS AND RESULTS: Patients (n = 909) treated for native coronary lesions were
      randomized into four groups: the control or the celecoxib group with
      stratification by stents: paclitaxel-eluting stent (PES) or zotarolimus-eluting
      stent (ZES). In the celecoxib group, 200 mg of celecoxib was given twice daily
      for 3 months after the procedure. The primary endpoint was in-stent late loss
      (LL) at 6 months. In-stent LL was significantly lower in the celecoxib group than
      the control group (0.64 +/- 0.54 vs. 0.55 +/- 0.47 mm, P = 0.02). The trend of LL
      reduction in the celecoxib group was maintained in the ZES and PES subgroups,
      although it did not reach statistical significance. There was a trend towards the
      reduced clinically driven TLR in the celecoxib group (5.7 vs. 3.2%, log-rank P =
      0.09), but adverse cardiac events rate did not differ between the two groups
      (composite of cardiac death, non-fatal myocardial infarction, and TLR; 8.6 vs.
      7.7%, log-rank P = 0.84). Non-fatal myocardial infarction and cardiac death
      occurred in 1.6% of the patients in the celecoxib group when compared with 0.2%
      in the control group (log-rank P = 0.03). CONCLUSION: Three-month adjunctive
      celecoxib would be useful to reduce LL of DES. However, this study may raise the
      concern about increased thrombotic risk with celecoxib even in patients receiving
      dual anti-platelet therapy.

PMID- 22408035
TI  - Imaging the right heart: the use of integrated multimodality imaging.
AB  - During recent years, right ventricular (RV) structure and function have been
      found to be an important determinant of outcome in different cardiovascular and
      also pulmonary diseases. Currently, echocardiography and cardiac magnetic
      resonance (CMR) imaging are the two imaging modalities most commonly used to
      visualize the RV. Most structural abnormalities of the RV can be reliably
      described by echocardiography but due its complex geometrical shape,
      echocardiographic assessment of RV function is more challenging. Newer promising
      echocardiographic techniques are emerging but lack of validation and limited
      normal reference data influence their routine clinical application. Cardiac
      magnetic resonance is generally considered the clinical reference technique due
      to its unlimited imaging planes, superior image resolution, and three-dimensional
      volumetric rendering. The accuracy and reliability of CMR measurements make it
      the ideal tool for serial examinations of RV function. Multidetector computed
      tomography (MDCT) plays an important role in the diagnosis of pulmonary emboli
      but can also be used for assessing RV ischaemic disease or as an alternative for
      CMR if contra-indicated. Radionuclide techniques have become more obsolete in the
      current era. The different imaging modalities should be considered complimentary
      and each plays a role for different indications.

PMID- 22408036
TI  - Non-alcoholic fatty liver disease: a new and important cardiovascular risk
      factor?
AB  - Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population
      worldwide and may confer increased cardiometabolic risk with consequent adverse
      cardiovascular outcomes independent of traditional cardiovascular risk factors
      and the metabolic syndrome. It is characterized almost universally by insulin
      resistance and is strongly associated with type 2 diabetes and obesity. Non
      alcoholic fatty liver disease is a marker of pathological ectopic fat
      accumulation combined with a low-grade chronic inflammatory state. This results
      in several deleterious pathophysiological processes including abnormal glucose,
      fatty acid and lipoprotein metabolism, increased oxidative stress, deranged
      adipokine profile, hypercoaguability, endothelial dysfunction, and accelerated
      progression of atherosclerosis. This ultimately leads to a dysfunctional
      cardiometabolic phenotype with cardiovascular mortality representing the main
      mode of premature death in NAFLD. This review is aimed at introducing NAFLD to
      the clinical cardiologist by discussing in-depth the evidence to date linking
      NAFLD with cardiovascular disease, reviewing the likely mechanisms underlying
      this association, as well as summarizing from a cardiologist's perspective,
      current and potential future treatment options for this increasingly prevalent
      disease.

PMID- 22408037
TI  - The impact of prosthesis-patient mismatch on long-term survival after aortic
      valve replacement: a systematic review and meta-analysis of 34 observational
      studies comprising 27 186 patients with 133 141 patient-years.
AB  - AIMS: Numerous studies have linked prosthesis-patient mismatch (PPM) after aortic
      valve replacement (AVR) to adverse outcomes. Its correlation with long-term
      survival has been described but with contradicting results. This systematic
      review and meta-analysis of observational studies aims to determine the hazard of
      PPM after AVR. METHODS AND RESULTS: The Medline and EMBase databases were
      searched for English-language original publications. Two researchers
      independently screened studies and extracted data. Pooled estimates were obtained
      by random effects model. Subgroup analyses were performed to detect sources of
      heterogeneity. The search yielded 348 potentially relevant studies; 34 were
      included comprising 27 186 patients and 133 141 patient-years. Defined by the
      universally accredited indexed effective orifice area <0.85 cm(2)/m(2), 44.2% of
      patients were categorized as having PPM. In 34.2 and 9.8% of patients moderate
      (0.65-0.85 cm(2)/m(2)) and severe (<0.65 cm(2)/m(2)) PPM was present,
      respectively. Prosthesis-patient mismatch was associated with a statistically
      significant increase in all-cause mortality (HR = 1.34, 95% CI: 1.18-1.51), but
      only a trend to an increase in cardiac-related mortality (HR = 1.51, 95% CI: 0.88
      2.60) was recognized. Analysis by severity of PPM demonstrated that both moderate
      and severe PPM increased all-cause mortality (HR = 1.19, 95% CI: 1.07-1.33 and HR
      = 1.84, 95% CI: 1.38-2.45) and cardiac-related mortality (HR = 1.32, 95% CI: 1.02
      1.71 and HR = 6.46, 95% CI: 2.79-14.97). Further analyses showed a consistent
      effect over separate time intervals during follow-up. CONCLUSION: Prosthesis
      patient mismatch is associated with an increase in all-cause and cardiac-related
      mortality over long-term follow-up. We recommend that current efforts to prevent
      PPM should receive more emphasis and a widespread acceptance to improve long-term
      survival after AVR.

PMID- 22408038
TI  - The effects of display time and eccentricity on the detection of amplitude and
      phase degradations in textured stimuli.
AB  - The amplitude and phase spectra of an image contain important information for
      perception, and a large body of work has investigated the effects of manipulating
      these spectra on the recognition or classification of image content. Here, we use
      a novel means of investigating sensitivity to amplitude and phase spectra
      properties, testing the ability of observers to detect degradations of the
      spectral content of synthetic images of textured surfaces that are broadband in
      the frequency domain. The effects of display time and retinal eccentricity on
      sensitivity to these two manipulations are compared using stimuli matched for
      difficulty of detection. We find no difference between the time courses for the
      detection of degradation in the two spectra; in both cases, accuracy rises above
      chance when display times are greater than 80 ms. Increasing retinal eccentricity
      to 8.7 degrees , however, has a significantly stronger effect on the accuracy of
      detecting degradations of the amplitude spectrum than of the phase spectrum.
      Further, sensitivity to phase randomization that is restricted to low spatial
      frequencies is greater in the periphery (at 8.7 degrees  eccentricity) than in
      the fovea. These last two results imply that the fovea and periphery are
      specialized for the processing of phase spectrum information in distinct spatial
      frequency bands.

PMID- 22408040
TI  - How we perceive the trajectory of an approaching object.
AB  - Various equations that describe how observers could recover the trajectory of an
      approaching object have been put forward. Many are relatively complex
      formulations that recover the veridical trajectory by scaling retinal cues, such
      as looming and changing disparity. However, these equations do not seem to
      describe human perception as observers typically misjudge trajectory angles.
      Thus, we examine whether a simpler formulation--one that does not predict
      veridical judgments-may better explain performance. We test the hypothesis that
      perceived trajectory is based on a speed ratio: the ratio of lateral angular
      speed to the sum of looming and changing disparity signals. To discriminate
      between this and alternative proposals, we examined the effect of object size on
      trajectory perception: The speed ratio hypothesis predicts that perceived
      trajectory will become less eccentric with increasing object size, while the
      alternatives predict that perceived trajectory will be independent of object
      size. Observers performed a trajectory judgment task in which they compared the
      trajectory direction of two approaching objects, of the same or different size,
      seen in separate intervals. We estimated perceptually parallel trajectories from
      their responses. In Experiment 1, objects differed in horizontal and vertical
      size, and in Experiment 2, they differed only in vertical size. In both
      experiments, observers' data showed a clear effect of object size and were close
      to predictions of the speed ratio hypothesis. We conclude that the alternate
      proposals we tested were not supported and that the speed ratio account is a
      sufficient account of the data.

PMID- 22408039
TI  - Deconstructing continuous flash suppression.
AB  - In this paper, we asked to what extent the depth of interocular suppression
      engendered by continuous flash suppression (CFS) varies depending on
      spatiotemporal properties of the suppressed stimulus and CFS suppressor. An
      answer to this question could have implications for interpreting the results in
      which CFS influences the processing of different categories of stimuli to
      different extents. In a series of experiments, we measured the selectivity and
      depth of suppression (i.e., elevation in contrast detection thresholds) as a
      function of the visual features of the stimulus being suppressed and the stimulus
      evoking suppression, namely, the popular "Mondrian" CFS stimulus (N. Tsuchiya &
      C. Koch, 2005). First, we found that CFS differentially suppresses the spatial
      components of the suppressed stimulus: Observers' sensitivity for stimuli of
      relatively low spatial frequency or cardinally oriented features was more
      strongly impaired in comparison to high spatial frequency or obliquely oriented
      stimuli. Second, we discovered that this feature-selective bias primarily arises
      from the spatiotemporal structure of the CFS stimulus, particularly within
      information residing in the low spatial frequency range and within the smooth
      rather than abrupt luminance changes over time. These results imply that this CFS
      stimulus operates by selectively attenuating certain classes of low-level signals
      while leaving others to be potentially encoded during suppression. These findings
      underscore the importance of considering the contribution of low-level features
      in stimulus-driven effects that are reported under CFS.

PMID- 22408041
TI  - Modeling center-surround configurations in population receptive fields using
      fMRI.
AB  - Antagonistic center-surround configurations are a central organizational
      principle of our visual system. In visual cortex, stimulation outside the
      classical receptive field can decrease neural activity and also decrease
      functional Magnetic Resonance Imaging (fMRI) signal amplitudes. Decreased fMRI
      amplitudes below baseline-0% contrast-are often referred to as "negative"
      responses. Using neural model-based fMRI data analyses, we can estimate the
      region of visual space to which each cortical location responds, i.e., the
      population receptive field (pRF). Current models of the pRF do not account for a
      center-surround organization or negative fMRI responses. Here, we extend the pRF
      model by adding surround suppression. Where the conventional model uses a
      circular symmetric Gaussian function to describe the pRF, the new model uses a
      circular symmetric difference-of-Gaussians (DoG) function. The DoG model allows
      the pRF analysis to capture fMRI signals below baseline and surround suppression.
      Comparing the fits of the models, an increased variance explained is found for
      the DoG model. This improvement was predominantly present in V1/2/3 and decreased
      in later visual areas. The improvement of the fits was particularly striking in
      the parts of the fMRI signal below baseline. Estimates for the surround size of
      the pRF show an increase with eccentricity and over visual areas V1/2/3. For the
      suppression index, which is based on the ratio between the volumes of both
      Gaussians, we show a decrease over visual areas V1 and V2. Using non-invasive
      fMRI techniques, this method gives the possibility to examine assumptions about
      center-surround receptive fields in human subjects.

PMID- 22408042
TI  - Lung development and the host response to influenza A virus are altered by
      different doses of neonatal oxygen in mice.
AB  - Oxygen exposure in preterm infants has been associated with altered lung
      development and increased risk for respiratory viral infections later in life.
      Although the dose of oxygen sufficient to exert these changes in humans remains
      unknown, adult mice exposed to 100% oxygen between postnatal days 1-4 exhibit
      alveolar simplification and increased sensitivity to influenza virus infection.
      Additionally, two nonlinear thresholds of neonatal oxygen exposures were
      previously identified that promote modest (between 40% and 60% oxygen) and severe
      (between 80% and 100% oxygen) changes in lung development. Here, we investigate
      whether these two thresholds correlate with the severity of lung disease
      following respiratory viral infection. Adult mice exposed to 100% oxygen at
      birth, and to a lesser extent 80% oxygen, demonstrated enhanced body weight loss,
      persistent inflammation, and fibrosis following infection compared with infected
      siblings exposed to room air at birth. In contrast, the host response to
      infection was indistinguishable between mice exposed to room air and 40% or 60%
      oxygen. Interestingly, levels of monocyte chemoattractant protein (MCP)-1 were
      equivalently elevated in infected mice that had been exposed to 80% or 100%
      oxygen as neonates. However, reducing levels of MCP-1 using heterozygous Mcp-1
      mice did not affect oxygen-dependent changes in the response to infection. Thus
      lung development and the host response to respiratory viral infection are
      disrupted by different doses of oxygen. Our findings suggest that measuring lung
      function alone may not be sufficient to identify individuals born prematurely who
      have increased risk for respiratory viral infection.

PMID- 22408043
TI  - Respiratory complications after oesophagectomy for cancer do not affect disease
      free survival.
AB  - OBJECTIVES: Recent studies have suggested that postoperative complications could
      have a potential negative effect on long-term outcome after oesophagectomy for
      cancer. Because respiratory failures represent the most frequent postoperative
      complication, we have investigated the prognostic impact of these complications
      on disease-free survival (DFS). METHODS: From a prospective single-institution
      database of 405 consecutive patients who underwent transthoracic oesophagectomy
      for cancer, we retrospectively analysed medical charts of all patients with
      microscopically complete resection (R0, n = 384 patients). Complications were
      graded according to the modified Clavien classification. Respiratory
      complications were defined as atelectasis, pneumonia or acute respiratory
      distress syndrome in the absence of early surgical complications. Patients with
      grade 5 (postoperative mortality, n = 43, 11%) were excluded from the analysis.
      The remaining 341 patients were analysed for estimation of DFS according to the
      Kaplan-Meier method. Logistic regression analysis was conducted to discriminate
      predictive factors affecting DFS. RESULTS: According to the modified Clavien
      classification, postoperative complications rates were grade 0: 147 (44%), grade
      1: 7 (2%), grade 2: 56 (16%), grade 3: 69 (20%) and grade 4: 62 (18%). Five-year
      DFS rates were not significantly different between grade 0 (no complication, 38%,
      n = 147) and other grades (grade 1, 2, 3 and 4 (64, 45, 56 and 48%,
      respectively)). Respiratory complications occurred in 107 patients (31%) and the
      5-year DFS in this subgroup was 47% compared with 38% observed in grade 0
      patients (P = 0.75). Clavien classification and respiratory complications did not
      come out in the univariate analysis of factors affecting DFS. On logistic
      regression, only two variables affected DFS: c-N stage and extracapular lymph
      node involvement. CONCLUSIONS: When postoperative mortality is excluded,
      postoperative complications do not affect DFS in patients with complete
      resection. This deserves substantial information regarding the prognosis of
      subgroup of patients in critical situations where incrementing intensive care is
      debated.

PMID- 22408044
TI  - No prominent role for terminal complement activation in the early myocardial
      reperfusion phase following cardiac surgery.
AB  - OBJECTIVES: Complement activation is considered an important mediator of
      myocardial ischaemia/reperfusion (I/R) injury. Although complement inhibitors are
      highly effective in animals, clinical trials fail to show a substantial benefit
      in humans. This raises questions on the role of complement activation in human
      myocardial I/R injury. METHODS: Soluble C5b-9, i.e. terminal complement complex,
      and C5a were assessed in patients with non-ischaemic (n = 10) and ischaemic heart
      failure (n = 10), and patients without heart failure (n = 10) undergoing cardiac
      surgery. To study the pathophysiology of human I/R injury, a model of
      arteriovenous measurements over the reperfused heart was applied at consecutive
      time points during the early reperfusion phase. Furthermore, C3d and C5b-9
      depositions in pre-reperfusion myocardial and endomyocardial tissue were
      evaluated and compared to pre-transplantation tissue from myocardial allografts.
      RESULTS: Simultaneous assessment of soluble C5b-9 and C5a in systemical and
      myocardial venous blood samples revealed the absence of net release from the
      reperfused heart in all three patient groups. Biopsies of patients with non
      ischaemic heart failure showed the most abundant myocardial depositions of C3d
      and C5b-9: 4.8 times more C3d (P = 0.008) and 4.7 times more C5b-9 (P = 0.004)
      than donor tissue. Also C3d was abundantly present in endomyocardial tissue of
      both heart failure groups compared to donors (both P = 0.02). CONCLUSIONS: No
      evidence was obtained that terminal complement activation is involved in the
      acute phase following myocardial reperfusion. Since complement deposition was
      already present before reperfusion, human complement inhibition might be more
      beneficial in the preoperative phase than during reperfusion.

PMID- 22408045
TI  - The association of ambient air pollution with airway inflammation in
      schoolchildren.
AB  - The biologic mechanisms involved in airway inflammatory response to air pollution
      are not clearly understood. The authors conducted a longitudinal study to
      investigate whether exposure to ambient air pollutants affected inflammatory
      cells and mediators from nasal lavage in schoolchildren. Study participants were
      100 elementary and middle-school students in New Taipei City, Taiwan. A
      structured respiratory health questionnaire was administered in September 2007,
      followed by monthly measurement of nasal inflammation from October 2007 to
      November 2009. During the study period, daily concentrations of air pollutants
      were obtained from the Environmental Protection Administration monitoring station
      and the Aerosol Supersite. Mixed-effects models were applied to examine the
      association between air pollution and nasal inflammatory cells and mediators,
      including percentages of neutrophils, eosinophils, and monocytes in lavaged cells
      and interleukin-8. A total of 824 measurements were obtained from 100
      participants over a period of 10 months. The level of particulate matter with an
      aerodynamic diameter of 2.5 MUm or less (PM(2.5)) was found to be associated with
      percentage of neutrophils (beta = 3.45%, 95% confidence interval: 0.89, 6.01) and
      interleukin-8 level (beta = 29.98 pg/mL, 95% confidence interval: 3.26, 56.69) in
      the nasal lavage on the day of exposure. In this longitudinal cohort study of
      schoolchildren, results indicated that exposure to PM(2.5) might induce nasal
      inflammation.

PMID- 22408046
TI  - Mosquirix (RTS,S): a novel vaccine for the prevention of Plasmodium falciparum
      malaria.
AB  - OBJECTIVE: To summarize and evaluate the literature for Mosquirix (RTS,S) and
      provide insight into the therapeutic and economic controversies of this novel
      malaria vaccine candidate. DATA SOURCES: A systematic literature search was
      performed using the terms Mosquirix; RTS,S; malaria; vaccine; and Plasmodium in
      MEDLINE (1948-November 2011), EMBASE (1980-November 2011), International
      Pharmaceutical Abstracts (1970-November 2011), Google, and Google Scholar. STUDY
      SELECTION AND DATA EXTRACTION: Clinical trials describing vaccine development,
      pharmacology, pharmacokinetics, efficacy, and safety were reviewed. For efficacy,
      clinical trials were reviewed that reported acquisition of malarial disease.
      Information regarding study design, population, study period, baseline
      characteristics, clinical outcomes, results, and assessors of quality was
      extracted. DATA SYNTHESIS: Five randomized controlled trials and 4 follow-up
      extension studies were identified. In Phase 2 trials, vaccine efficacy rates were
      33-65% in infants and 30-53% in children for preventing the first episode of
      clinical disease. In Phase 3 trials, vaccine efficacy was 56% in children aged 5
      17 months. RTS,S reduced the number of clinical malaria episodes and prevented
      severe malaria in several studies. The follow-up period for vaccine efficacy
      ranged from 6 to 45 months. RTS,S 25 MUg is administered intramuscularly as 3
      injections given 1 month apart for infants and children. RTS,S appears to be
      generally well tolerated. A few cases of meningitis and seizures (within 7 days
      of vaccination) have been reported. CONCLUSIONS: RTS,S has demonstrated efficacy
      and safety in Phase 1, 2, and 3 trials, and has the potential to decrease
      morbidity and mortality from malaria worldwide. Major challenges include
      determination of the duration of immunity, assessment of its cost-effectiveness,
      its use in special populations, and its dissemination in endemic regions. Pending
      further studies, RTS,S has the potential to become the benchmark as the first
      effective vaccine against malaria.

PMID- 22408047
TI  - Disabling synovitis associated with LARS artificial ligament use in anterior
      cruciate ligament reconstruction: a case report.

PMID- 22408048
TI  - A 15-year prospective epidemiological account of acute traumatic injuries during
      official professional soccer league matches in Japan.
AB  - BACKGROUND: Few prospective epidemiological studies on soccer match injuries have
      collected continuous data using subjects from the same group. PURPOSE: To
      investigate long-term injury-induced changes during official matches in the
      professional Japanese soccer league. STUDY DESIGN: Descriptive epidemiological
      study. METHODS: Acute injuries during official matches among top-division
      Japanese professional soccer leaguers were prospectively collected from 1993 to
      2007. Injuries preventing player participation for 7 days or more were defined as
      a reportable injury. Interseasonal variations of injury rate (IR:
      injuries/1000/player hours) and injury pattern (type, location, circumstances,
      severity, injury time, positional role, and relationship to weather) were
      analyzed. RESULTS: Throughout the study period, 2947 injuries from 3984 matches
      occurred. Mean annual IR was 21.77/1000 player hours, and annual variance showed
      gradual decrement throughout the study period. The proportion of injury type and
      location were not significantly changed. Sprain and contusion as injury type and
      thigh and ankle joint as location were the most common in every season. Contact
      related injuries comprised 73.3% on average and were observed to occur more
      frequently during the last 15 minutes and extra time of match play. The
      proportion of foul play-related injuries showed a clear declining trend. The
      proportion of severe injury showed a sporadic increase from 2001 to 2004. The
      second, fifth, and sixth 15-minute match segments showed a higher IR. Goalkeepers
      had a lower IR versus other field players. Matches on rainy days resulted in a
      lower IR than did those held under other weather conditions. CONCLUSION: Long
      term surveillance and statistical feedback of injury characteristics to
      organization members were considered effective in improving safer play awareness
      among players and for referees to reduce injury incidence, particularly foul play
      related injuries.

PMID- 22408050
TI  - Two-stage k-sample designs for the ordered alternative problem.
AB  - In preclinical studies and clinical dose-ranging trials, the Jonckheere-Terpstra
      test is widely used in the assessment of dose-response relationships. Hewett and
      Spurrier (1979) presented a two-stage analog of the test in the context of large
      sample sizes. In this paper, we propose an exact test based on Simon's minimax
      and optimal design criteria originally used in one-arm phase II designs based on
      binary endpoints. The convergence rate of the joint distribution of the first and
      second stage test statistics to the limiting distribution is studied, and design
      parameters are provided for a variety of assumed alternatives. The behavior of
      the test is also examined in the presence of ties, and the proposed designs are
      illustrated through application in the planning of a hypercholesterolemia
      clinical trial. The minimax and optimal two-stage procedures are shown to be
      preferable as compared with the one-stage procedure because of the associated
      reduction in expected sample size for given error constraints.

PMID- 22408052
TI  - Longitudinal variation in adolescent physical activity patterns and the emergence
      of tobacco use.
AB  - OBJECTIVE: The objective of this investigation was to examine how variation in
      adolescent physical activity is related to smoking and alternative tobacco use.
      METHODS: Adolescents (N = 1,384) completed a self-report survey every 6 months
      from ages 14- to 18-years old in a prospective study of health behaviors. The 8
      waves of data were analyzed using General Growth Mixture Modeling (GGMM) 
      RESULTS: GGMM identified five physical activity trajectories including stable
      higher (SHPA), decreased (DPA), stable regular (SRPA), curvilinear (CPA), and
      stable low (SLPA). Across 4 years, the likelihood of smoking was greater among
      adolescents in the DPA, SLPA and SRPA trajectories compared to adolescents
      belonging to the SHPA trajectory. Alternative tobacco use was greatest among
      adolescents in the DPA and SRPA trajectories. CONCLUSIONS: Adolescents with
      decreasing physical activity and even adolescents averaging an hour of physical
      activity a day (SRPA) are important groups to target for tobacco use prevention
      and intervention efforts.

PMID- 22408053
TI  - Identifying individual, cultural and asthma-related risk and protective factors
      associated with resilient asthma outcomes in urban children and families.
AB  - OBJECTIVE: The goal of this study is to identify individual, family/cultural, and
      illness-related protective factors that may minimize asthma morbidity in the
      context of multiple urban risks in a sample of inner-city children and families.
      METHODS: Participating families are from African-American (33), Latino (51) and
      non-Latino white (47) backgrounds. A total of 131 children with asthma (56%
      male), ages 6-13 years and their primary caregivers were included. RESULTS:
      Analyses supported the relationship between cumulative risks and asthma morbidity
      across children of the sample. Protective processes functioned differently by
      ethnic group. For example, Latino families exhibited higher levels of family
      connectedness, and this was associated with lower levels of functional limitation
      due to asthma, in the context of risks. CONCLUSIONS: This study demonstrates the
      utility of examining multilevel protective processes that may guard against urban
      risks factors to decrease morbidity. Intervention programs for families from
      specific ethnic groups can be tailored to consider individual, family
      based/cultural and illness-related supports that decrease stress and enhance
      aspects of asthma treatment.

PMID- 22408054
TI  - Helpful hints: caregiver-generated asthma management strategies and their
      relation to pediatric asthma symptoms and quality of life.
AB  - OBJECTIVE: This mixed-methods study examined the relation between caregiver
      generated asthma management strategies and asthma severity in a sample of 200
      children with persistent asthma (ages 5-12 years). METHODS: Caregivers were
      interviewed about asthma management strategies they found helpful in controlling
      their child's symptoms. A qualitative content analysis was used to identify
      household strategies. Indicators of asthma severity included lung functioning
      (FEV(1)) and functional severity (FSS). Child quality of life was also assessed
      (PQLQ). RESULTS: Six primary household strategies were identified: Reactive,
      Planning Ahead, Social, Emotional, Avoiding Triggers, and Cleaning. In general,
      strategies offered by caregivers did not differ by socioeconomic status.
      Caregivers who endorsed Avoiding Triggers as effective strategies had children
      with better lung functioning. Caregivers who endorsed Planning Ahead or Emotional
      strategies had children with better asthma-related quality of life. CONCLUSION:
      These household strategies hold promise for reducing pediatric asthma symptoms
      and improving child quality of life.

PMID- 22408055
TI  - Social-emotional difficulties in very preterm and term 2 year olds predict
      specific social-emotional problems at the age of 5 years.
AB  - BACKGROUND: Very preterm children have increased risk for social-emotional
      problems. This study examined relationships between early social-emotional
      difficulties and later social-emotional problems, and whether this differed by
      group (very preterm or term). METHODS: Participants were 189 children born less
      than 30 weeks gestation or less than 1,250 g at birth and 78 term-born children.
      Parent-report questionnaires were used to assess social-emotional development at
      2 (infant toddler social emotional assessment) and 5 years of age (strengths and
      difficulties questionnaire). Social risk and children's cognitive development
      were collected at the age of 5 years. RESULTS: Emotional symptoms at the age of 5
      years were predicted by internalizing problems at the age of 2 years, conduct
      problems and hyperactivity/inattention at the age of 5 years were predicted by
      externalizing problems at the age of 2 years, and peer relationship problems and
      prosocial behaviors at the age of 5 years were predicted by social-emotional
      competence at the age of 2 years. Relationships were not moderated by group.
      CONCLUSIONS: Implications for early detection of social-emotional problems and
      provision of targeted interventions are discussed.

PMID- 22408056
TI  - Commentary: medicaid reimbursement and utilization of health and behavior codes:
      year one in Oklahoma.

PMID- 22408057
TI  - Trajectories of maternal mental health: a prospective study of mothers of infants
      with congenital heart defects from pregnancy to 36 months postpartum.
AB  - OBJECTIVE: To chart mothers' trajectories of mental health from pregnancy to 36
      months postpartum in order to investigate the association between infants'
      congenital heart defects (CHD) and compromised maternal mental health. METHODS:
      Mothers of infants with mild, moderate, or severe CHD (n = 141) and mothers (n =
      36,437) enrolled in the Norwegian Mother and Child Cohort Study were assessed at
      regular intervals from pregnancy up to 36 months postpartum, including
      measurements at 6 and 18 months, using an 8-item version of the Hopkins Symptom
      Checklist-25. RESULTS: Mean score trajectories of SCL-8 for mothers of infants
      with severe CHD deviated significantly from cohort controls 6, 18, and 36 months
      postpartum, indicating heightened symptoms of depression and anxiety.
      CONCLUSIONS: Mothers of infants with severe CHD are at risk of compromised mental
      health from delivery to 36 months postpartum. Strain due to CHD-related
      interventions is identified as a possible partial mediator of the distress.

PMID- 22408059
TI  - Selective isotopic unlabeling of proteins using metabolic precursors: application
      to NMR assignment of intrinsically disordered proteins.
AB  - Selective isotopic unlabeling of proteins can provide important residue-type
      information as well as reduce congestion of NMR spectra. However, metabolic
      scrambling often complicates the final isotope-labeling pattern. Here, an array
      of metabolic precursors is used to perform robust, residue-specific unlabeling of
      proteins. The resulting isotopic-labeling patterns are predictable and nicely
      complement NMR experiments that differentiate residue types. This approach has
      widespread applications, but it is particularly relevant for proteins that lack
      sequence complexity or a defined tertiary structure.

PMID- 22408058
TI  - CD133 marks a myogenically primitive subpopulation in rhabdomyosarcoma cell lines
      that are relatively chemoresistant but sensitive to mutant HSV.
AB  - BACKGROUND: Rhabdomyosarcoma (RMS) is characterized by features of skeletal
      muscle and is comprised of two major histological subtypes, embryonal (E-RMS),
      and alveolar (A-RMS). Subsets of each RMS subtype demonstrate resistance to
      multimodal therapy leading to treatment failure. Cancer stem cells or cancer
      initiating cells (CIC) represent a theorized population of cells that give rise
      to tumors and are responsible for treatment resistance. PROCEDURE: We
      investigated the ability of CD133, a putative CIC marker, to distinguish a
      chemoresistant, myogenically primitive population in alveolar (RH30), and
      embryonal (RD) RMS cell lines. We tested CD133+/- cells for sensitivity to
      engineered herpes simplex virus (oHSV). RESULTS: Relative to CD133- cells, CD133+
      A-RMS, and E-RMS cells demonstrate an enhanced colony-forming ability, are less
      differentiated myogenically, and are more resistant to cytotoxic chemotherapy but
      equally sensitive to oHSV oncolysis. Compared to CD133- RD cells, CD133+ cells
      express relatively high levels of genes typically expressed in skeletal muscle
      progenitor satellite cells including PAX7, c-MET, and the GLI effectors of the
      hedgehog signaling pathway. In contrast, CD133+ RH30 cells were not associated
      with enhanced expression of satellite cell markers or Hh targets. CONCLUSIONS:
      Our findings demonstrate that CD133+ cells from A-RMS and E-RMS cell lines are
      characterized by a myogenically primitive phenotype. These cells have the
      capacity to form colonies in vitro and are more resistant to chemotherapy than
      CD133- cells. CD133 expression may denote a subset of RMS cells with an important
      role in tumorigenesis and treatment failure. These resistant cells may be
      effectively targeted by oHSV therapy.

PMID- 22408060
TI  - Pediatric brain tumors: gene X environment interactions providing new clues?

PMID- 22408061
TI  - The 5-hydroxytryptamine4 receptor agonists prucalopride and PRX-03140 increase
      acetylcholine and histamine levels in the rat prefrontal cortex and the power of
      stimulated hippocampal theta oscillations.
AB  - 5-Hydroxytryptamine (5-HT)(4) receptor agonists reportedly stimulate brain
      acetylcholine (ACh) release, a property that might provide a new pharmacological
      approach for treating cognitive deficits associated with Alzheimer's disease. The
      purpose of this study was to compare the binding affinities, functional
      activities, and effects on neuropharmacological responses associated with
      cognition of two highly selective 5-HT(4) receptor agonists, prucalopride and 6,7
      dihydro-4-hydroxy-7-isopropyl-6-oxo-N-[3-(piperidin-1-yl)propyl]thieno[2,3
      b]pyridine-5-carboxamide (PRX-03140). In vitro, prucalopride and PRX-03140 bound
      to native rat brain 5-HT(4) receptors with K(i) values of 30 nM and 110 nM,
      respectively, and increased cAMP production in human embryonic kidney-293 cells
      expressing recombinant rat 5-HT(4) receptors. In vivo receptor occupancy studies
      established that prucalopride and PRX-03140 were able to penetrate the brain and
      bound to 5-HT(4) receptors in rat brain, achieving 50% receptor occupancy at free
      brain exposures of 330 nM and 130 nM, respectively. Rat microdialysis studies
      revealed that prucalopride maximally increased ACh and histamine levels in the
      prefrontal cortex at 5 and 10 mg/kg, whereas PRX-03140 significantly increased
      cortical histamine levels at 50 mg/kg, failing to affect ACh release at doses
      lower than 150 mg/kg. In combination studies, donepezil-induced increases in
      cortical ACh levels were potentiated by prucalopride and PRX-03140.
      Electrophysiological studies in rats demonstrated that both compounds increased
      the power of brainstem-stimulated hippocampal theta oscillations at 5.6 mg/kg.
      These findings show for the first time that the 5-HT(4) receptor agonists
      prucalopride and PRX-03140 can increase cortical ACh and histamine levels,
      augment donepezil-induced ACh increases, and increase stimulated-hippocampal
      theta power, all neuropharmacological parameters consistent with potential
      positive effects on cognitive processes.

PMID- 22408062
TI  - Directed evolution of subtilisin E into a highly active and guanidinium chloride-
      and sodium dodecylsulfate-tolerant protease.
AB  - Proteases have niche applications in diagnostic kits that use cell lysis and
      thereby require high resistance towards chaotropic salts and detergents, such as
      guanidinium chloride (GdmCl) and sodium dodecylsulfate (SDS). Subtilisin E, a
      well-studied serine protease, was selected to be re-engineered by directed
      evolution into a "chaophilic" protease that would be resistance to GdmCl and SDS,
      for application in diagnostic kits. In three iterative rounds of directed
      evolution, variant SeSaM1-5 (S62I/A153V/G166S/I205V) was generated, with improved
      activity (330 %) and increased half life in 1 M GdmCl (<2 min to 4.7 h) or in 0.5
      % SDS (<2 min to 2.7 h). Saturation mutagenesis at each site in the wild-type
      subtilisin E revealed that positions 62 and 166 were mainly responsible for
      increased activity and stability. A double mutant, M2 (S62I/G166M), generated by
      combination of the best single mutations showed significantly improved kinetic
      constants; in 2 M GdmCl the K(m) value decreased (29-fold) from 7.31 to 0.25 mM,
      and the k(cat) values increased (fourfold) from 15 to 61 s(-1) . The catalytic
      efficiency, k(cat)/K(m), improved dramatically (GdmCl: 247 mM(-1)s(-1) (118
      fold); SDS, 179 mM(-1)s(-1) (13-fold)). In addition, the SeSaM1-5 variant showed
      higher stability in 2.0 % SDS when compared to the wild-type (t(1/2) 54.8 min
      (>27-fold)). Finally, molecular dynamics simulations of the wild-type subtilisin
      E showed that Gdm(+) ions could directly interact with active site residues,
      thereby probably limiting access of the substrate to the catalytic centre.

PMID- 22408063
TI  - Perceived control over physical and mental well-being: the effects of gender, age
      and social class.
AB  - In a cross-sectional quota based survey 1013 adults (46% male, 54% female; aged
      16-65+) in Northern Ireland from ABC1, C2 and DE social class groupings were
      asked about the perceived influence they have over their physical and mental
      health, and what types of lifestyle changes can improve health. Findings showed
      participants perceive that they have more control over their physical compared to
      mental health, with physical activity being the behaviour most likely to be
      adopted. Females were more likely than males to make lifestyle changes, including
      meeting friends, talking about things that were bothering them and trying
      relaxation techniques. These findings illustrate the need for health promotion to
      be directed at mental health, and encouraging males to consider adapting healthy
      lifestyle behaviours.

PMID- 22408064
TI  - Bounded autonomy in deciding to seek medical help: carer role, the sick role and
      the case of dementia.
AB  - Social psychological theories of illness and health decision making place the
      individual with the symptoms at the centre. In the case of dementia it is often a
      relative who is first to contact health care professionals. The article
      illustrates how the autonomy of both the individual with symptoms and their
      carers is bounded by the actions of others. An over arching theme of 'bounded
      autonomy in decision making', and four subthemes emerged. Bounded autonomy is
      where a person's actions are constrained or contested by another person. There
      are implications for interventions to bring forward the point at which diagnosis
      occurs.

PMID- 22408065
TI  - Cranial nerve palsies in childhood parameningeal rhabdomyosarcoma.
AB  - BACKGROUND: Children with parameningeal rhabdomyosarcoma (PM RMS) and cranial
      nerve palsy (CNP) are at risk for permanent neurologic dysfunction. Clinicians
      often consider the use of emergent therapies such as expedited radiation and/or
      corticosteroids; however, there is a paucity of information describing the
      natural history of CNP in PM RMS. We sought to describe the clinical features of
      patients with PM RMS plus associated CNP and to evaluate the patient, disease,
      and treatment-related factors that impacted neurologic recovery. METHODS: We
      conducted a retrospective review of PM RMS cases treated at the Hospital for Sick
      Children between 1985 and 2010. RESULTS: Thirty-five children were treated for PM
      RMS, 19 (54%) of whom presented with CNP. Children with CNP were nine times more
      likely to have other high-risk features (cranial base bony erosion and/or
      intracranial extension) at the time of presentation than children without CNP (OR
      9.6, 95% CI 1.69, 54.79, P = 0.013). In addition to commencing chemotherapy, 13
      patients (68%) received expedited RT and corticosteroids, four (21%)
      corticosteroids alone, and two (11%) received only standard chemotherapy and RT.
      At last follow up of the 11 survivors, neurologic recovery was complete in five
      (45%), partial in five (45%), and absent in one (9%). CONCLUSIONS: In our cohort,
      recovery of PM RMS associated CNP was often incomplete despite multi-modal
      therapy. A larger cohort of patients is required to determine the utility of
      emergent initiation of radiation or corticosteroids. This study will facilitate
      the counseling of future families on the long-term neurologic recovery CNP in PM
      RMS.

PMID- 22408066
TI  - Effect of N3 modifications on the affinity of spin label c for abasic sites in
      duplex DNA.
AB  - Noncovalent site-directed spin labeling (NC-SDSL) of abasic sites in duplex DNAs
      with the spin label c, a cytosine analogue, is a promising approach for spin
      labeling nucleic acids for EPR spectroscopy. In an attempt to increase the
      affinity of c for abasic sites, several N3 derivatives were prepared, and their
      binding affinities were determined by EPR spectroscopy. Most of the N3
      substituents had a detrimental effect on binding. The triazole-linked
      polyethylene-glycol derivative (12 a) showed a 15-fold decrease in affinity,
      whereas the binding affinities of ethyl azido (8 b) and hydroxyl (8 c)
      derivatives were five- to sixfold lower. The spin-labeled nucleoside C showed
      only a twofold decrease, thus binding better than 8 c, even though it contains
      the larger 2'-deoxyribose substituent at N3 instead of a 2-hydroxyethyl group. N3
      derivatives that contained the basic ethyl amino (9) or ethyl guanidino (10)
      substituents had both higher binding affinity and solubility, attributed to their
      cationic charge at neutral pH. Compounds 9 and 10 are promising candidates for NC
      SDSL of nucleic acids, for distance measurements by pulsed EPR spectroscopy.

PMID- 22408067
TI  - The importance of distinguishing between black Caribbeans and Africans in
      understanding sexual risk and care-seeking behaviours for sexually transmitted
      infections: evidence from a large survey of people attending genitourinary
      medicine clinics in England.
AB  - BACKGROUND: In the UK, black Caribbean and African populations experience
      disproportionately high rates of sexually transmitted infections (STIs) and HIV.
      Often studies do not differentiate between these populations notwithstanding
      differences in STI epidemiology and sociodemographics. METHODS: Patterns of care
      seeking behaviour for STIs were explored separately for black Caribbean (n =
      345), black African (n = 193) and white people through a cross-sectional survey
      of 2824 people attending five genitourinary medicine (GUM) clinics in England.
      RESULTS: Black Caribbean men were least likely to use, or try to use, their
      general practice surgery prior to GUM clinic attendance (16.6%). Symptomatic
      black Caribbean and African men were least likely to delay seeking care (30.8 and
      26.3%, respectively). Symptomatic black Caribbean men faced the least provider
      delay in accessing care (27.3%). Black Caribbean men and women were most likely,
      and black African men and women least likely, to be diagnosed with an STI (49.7
      and 32.0% versus 26.8 and 16.3%, respectively). Among symptomatic women, black
      Caribbeans and, among symptomatic men, black Africans were most likely to report
      abstaining from sex (46.3 and 73.1%, respectively). CONCLUSIONS: Our analyses
      highlight the importance of distinguishing between black ethnic groups and the
      need for future studies to ensure sufficiently large samples to permit such
      analyses.

PMID- 22408068
TI  - New biodegradable small-diameter artificial vascular prosthesis: a feasibility
      study.
AB  - An in-house built instrument was used to fabricate a small internal diameter (2
      mm) artificial vascular prosthesis from biodegradable chitosan. This new
      artificial vascular prosthesis has shown a good biocompatibility based on the
      studies of its cell compatibility, inflammatory reaction, and platelet adhesion.
      In an animal test, the prosthesis was used to replace a 4-cm-long section of
      femoral artery in each of the seven tested dogs. The patency of the replacement
      was monitored at regular intervals using Doppler ultrasound diagnostics. Nine
      months after the implantation, hematoxylin and eosin staining,
      immunohistochemical study, and scanning electron microscope observation were
      carried out. Complete decomposition of the prosthesis and replacement by a
      natural blood vessel were observed. The results suggests that the artificial
      vascular prosthesis displays many characteristics of the "ideal" small-diameter
      artificial vascular, and have the biocompatibility that can be tailored to match
      those desired in vascular replacement application.

PMID- 22408069
TI  - Toxicological effects of a mixture used in weight loss products: p-synephrine
      associated with ephedrine, salicin, and caffeine.
AB  - p-Synephrine is an adrenergic amine found in Citrus aurantium L. fruits and has
      been used for weight loss in dietary supplements. There are commercial products
      containing this substance associated to caffeine, salicin, and ephedrine. The aim
      of this study was to evaluate the acute toxicity of this mixture in mice of both
      sexes. The significative results observed after acute oral administration to male
      and female mice of 300, 350, and 400 mg/kg total of p-synephrine, ephedrine,
      salicin, plus caffeine in a 10:4:6:80 w/w ratio included a reduction in locomotor
      activity and ptosis in all treated groups for both sexes. Seizures were also
      observed in male (400 mg/kg) and female groups (350 and 400 mg/kg). Gasping and
      tearing were observed in males. Salivation (400 mg/kg), agitation (350 and 400
      mg/kg), and piloerection (all treated groups) were significantly observed only in
      females. Deaths occurred in males at 350 and 400 mg/kg treated groups and the
      necropsy showed cardiopulmonary hemorrhage. A reduction in locomotor activity was
      confirmed through the spontaneous locomotor activity test, in which the number of
      crossings considerably decreased (P < .01) in all treated groups. The rotarod
      test showed a decrease in motor coordination at 400 mg/kg. Body temperature
      decreased significantly (P < .01) in all treated groups compared to controls. The
      results suggested clear signs of toxicity of p-synephrine, ephedrine, salicin,
      and caffeine association; this toxicity augments the attentiveness on commercial
      products containing this mixture, given the expressive number of adverse events
      related to its utilization.

PMID- 22408070
TI  - Improvement of the cytocompatibility of electrospun poly[(R)-3-hydroxybutyrate-co
      (R)-3-hydroxyvalerate] mats by Ecoflex.
AB  - Poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyvalerate] (PHBV) is a nature-derived
      polyester with potential application in tissue engineering scaffolds. However,
      PHBV is associated with disadvantages including high brittleness, slow
      degradation, high hydrophobicity, and unsatisfactory biocompatibility. In this
      study, we sought to improve the properties of PHBV by blending it with Ecoflex, a
      synthetic biopolyester with a high flexibility, fast degradation, and
      comparatively higher hydrophilicity. PHBV was codissolved with Ecoflex in
      dichloromethane at different mass ratios (PHBV/Ecoflex: 100/0, 70/30, 50/50, and
      30/70) and electrospun into mats. Compared with the pure PHBV mat, the Ecoflex
      containing mats showed decreased contact angles with phosphate-buffered saline
      (PBS), accelerated weight loss in PBS, and increased strain at break with
      increasing Ecoflex mass ratios. In vitro cell culture also showed significantly
      improved adhesion and proliferation of human bone marrow stroma cells with the
      introduction of Ecoflex. Blending PHBV with Ecoflex is a simple and effective
      method to improve the chemical, mechanical, and biological properties of PHBV
      simultaneously and thereby to expedite its application in tissue engineering. To
      our knowledge, this is the first report showing the biocompatibility of Ecoflex
      containing materials with human cells.

PMID- 22408071
TI  - Genetic control of seed shattering in rice by the APETALA2 transcription factor
      shattering abortion1.
AB  - Seed shattering is an important agricultural trait in crop domestication. SH4
      (for grain shattering quantitative trait locus on chromosome 4) and qSH1 (for
      quantitative trait locus of seed shattering on chromosome 1) genes have been
      identified as required for reduced seed shattering during rice (Oryza sativa)
      domestication. However, the regulatory pathways of seed shattering in rice remain
      unknown. Here, we identified a seed shattering abortion1 (shat1) mutant in a wild
      rice introgression line. The SHAT1 gene, which encodes an APETALA2 transcription
      factor, is required for seed shattering through specifying abscission zone (AZ)
      development in rice. Genetic analyses revealed that the expression of SHAT1 in AZ
      was positively regulated by the trihelix transcription factor SH4. We also
      identified a frameshift mutant of SH4 that completely eliminated AZs and showed
      nonshattering. Our results suggest a genetic model in which the persistent and
      concentrated expression of active SHAT1 and SH4 in the AZ during early spikelet
      developmental stages is required for conferring AZ identification. qSH1
      functioned downstream of SHAT1 and SH4, through maintaining SHAT1 and SH4
      expression in AZ, thus promoting AZ differentiation.

PMID- 22408072
TI  - Alternative splicing mediates responses of the Arabidopsis circadian clock to
      temperature changes.
AB  - Alternative splicing plays crucial roles by influencing the diversity of the
      transcriptome and proteome and regulating protein structure/function and gene
      expression. It is widespread in plants, and alteration of the levels of splicing
      factors leads to a wide variety of growth and developmental phenotypes. The
      circadian clock is a complex piece of cellular machinery that can regulate
      physiology and behavior to anticipate predictable environmental changes on a
      revolving planet. We have performed a system-wide analysis of alternative
      splicing in clock components in Arabidopsis thaliana plants acclimated to
      different steady state temperatures or undergoing temperature transitions. This
      revealed extensive alternative splicing in clock genes and dynamic changes in
      alternatively spliced transcripts. Several of these changes, notably those
      affecting the circadian clock genes late elongated hypocotyl (LHY) and pseudo
      response regulator7, are temperature-dependent and contribute markedly to
      functionally important changes in clock gene expression in temperature
      transitions by producing nonfunctional transcripts and/or inducing nonsense
      mediated decay. Temperature effects on alternative splicing contribute to a
      decline in LHY transcript abundance on cooling, but LHY promoter strength is not
      affected. We propose that temperature-associated alternative splicing is an
      additional mechanism involved in the operation and regulation of the plant
      circadian clock.

PMID- 22408073
TI  - The Arabidopsis E3 ubiquitin ligase HOS1 negatively regulates CONSTANS abundance
      in the photoperiodic control of flowering.
AB  - The Arabidopsis thaliana early in short days6 (esd6) mutant was isolated in a
      screen for mutations that accelerate flowering time. Among other developmental
      alterations, esd6 displays early flowering in both long- and short-day
      conditions. Fine mapping of the mutation showed that the esd6 phenotype is caused
      by a lesion in the high expression of osmotically responsive genes1 (HOS1) locus,
      which encodes a RING finger-containing E3 ubiquitin ligase. The esd6/hos1
      mutation causes decreased flowering locus C expression and requires CONSTANS (CO)
      protein for its early flowering phenotype under long days. Moreover, CO and HOS1
      physically interact in vitro and in planta, and HOS1 regulates CO abundance,
      particularly during the daylight period. Accordingly, hos1 causes a shift in the
      regular long-day pattern of expression of flowering locus T (FT) transcript,
      starting to rise 4 h after dawn in the mutant. In addition, HOS1 interacts
      synergistically with constitutive photomorphogenic1, another regulator of CO
      protein stability, in the regulation of flowering time. Taken together, these
      results indicate that HOS1 is involved in the control of CO abundance, ensuring
      that CO activation of FT occurs only when the light period reaches a certain
      length and preventing precocious flowering in Arabidopsis.

PMID- 22408074
TI  - Physiological genomics of response to soil drying in diverse Arabidopsis
      accessions.
AB  - Arabidopsis thaliana, like many species, is characterized by abundant genetic
      variation. This variation is rapidly being cataloged at the sequence level, but
      careful dissection of genetic variation in whole-organism responses to stresses
      encountered in the natural environment are lacking; this functional variation can
      be exploited as a natural mutant screen to determine gene function. Here, we
      document physiological and transcriptomic response to soil drying in 17 natural
      accessions of Arabidopsis. By imposing ecologically realistic stress conditions,
      we found that acclimation in Arabidopsis involved a strong signature of increased
      investment in photosynthesis, carbohydrate turnover, and root growth. Our results
      extend previous work in the Columbia accession suggesting that abscisic acid
      signaling pathways play an important role in drought stress response. We also
      identified several mechanisms, including an increase in leaf nitrogen
      concentration and upregulation of two-component signaling relays, that were
      common to most natural accessions but had not been identified in studies using
      only the Columbia accession. Principal component analysis reveals strong
      correlations between suites of genes and specific physiological responses to
      stress. The functional variants we identified may represent adaptive mutations in
      natural habitats and useful variants for agronomic improvement of crop species.

PMID- 22408075
TI  - SHAT1, A new player in seed shattering of rice.

PMID- 22408076
TI  - The MADS29 transcription factor regulates the degradation of the nucellus and the
      nucellar projection during rice seed development.
AB  - The MADS box transcription factors are critical regulators of rice (Oryza sativa)
      reproductive development. Here, we here report the functional characterization of
      a rice MADS box family member, MADS29, which is preferentially expressed in the
      nucellus and the nucellar projection. Suppressed expression of MADS29 resulted in
      abnormal seed development; the seeds were shrunken, displayed a low grain-filling
      rate and suppressed starch biosynthesis, and contained abnormal starch granules.
      Detailed analysis indicated that the abnormal seed development is due to
      defective programmed cell death (PCD) of the nucellus and nucellar projection,
      which was confirmed by a TUNEL assay and transcriptome analysis. Further studies
      showed that expression of MADS29 is induced by auxin and MADS29 protein binds
      directly to the putative promoter regions of genes that encode a Cys protease and
      nucleotide binding site-Leu-rich repeat proteins, thereby stimulating the PCD.
      This study identifies MADS29 as a key regulator of early rice seed development by
      regulating the PCD of maternal tissues. It provides informative clues to
      elucidate the regulatory mechanism of maternal tissue degradation after
      fertilization and to facilitate the studies of endosperm development and seed
      filling.

PMID- 22408077
TI  - A microRNA superfamily regulates nucleotide binding site-leucine-rich repeats and
      other mRNAs.
AB  - Analysis of tomato (Solanum lycopersicum) small RNA data sets revealed the
      presence of a regulatory cascade affecting disease resistance. The initiators of
      the cascade are microRNA members of an unusually diverse superfamily in which
      miR482 and miR2118 are prominent members. Members of this superfamily are
      variable in sequence and abundance in different species, but all variants target
      the coding sequence for the P-loop motif in the mRNA sequences for disease
      resistance proteins with nucleotide binding site (NBS) and leucine-rich repeat
      (LRR) motifs. We confirm, using transient expression in Nicotiana benthamiana,
      that miR482 targets mRNAs for NBS-LRR disease resistance proteins with coiled
      coil domains at their N terminus. The targeting causes mRNA decay and production
      of secondary siRNAs in a manner that depends on RNA-dependent RNA polymerase 6.
      At least one of these secondary siRNAs targets other mRNAs of a defense-related
      protein. The miR482-mediated silencing cascade is suppressed in plants infected
      with viruses or bacteria so that expression of mRNAs with miR482 or secondary
      siRNA target sequences is increased. We propose that this process allows pathogen
      inducible expression of NBS-LRR proteins and that it contributes to a novel layer
      of defense against pathogen attack.

PMID- 22408079
TI  - Commitments, norms and custard creams - a social influence approach to reducing
      did not attends (DNAs).

PMID- 22408078
TI  - The role of a 14-3-3 protein in stomatal opening mediated by PHOT2 in
      Arabidopsis.
AB  - The 14-3-3 lambda isoform is required for normal stomatal opening mediated by
      PHOT2 in Arabidopsis thaliana. Arabidopsis phototropin2 (PHOT2) interacts with
      the lambda-isoform 14-3-3 protein both in yeast two-hybrid screening and in an in
      vitro pull-down assay. Further yeast two-hybrid analysis also showed that the
      PHOT2 C-terminal kinase domain was required for the interaction. Site-directed
      mutagenesis indicated that PHOT2 Ser-747 is essential for the yeast interaction.
      Phenotypic characterization of a loss-of-function 14-3-3 lambda mutant in a phot1
      mutant background showed that the 14-3-3 lambda protein was necessary for normal
      PHOT2-mediated blue light-induced stomatal opening. PHOT2 Ser-747 was necessary
      for complementation of the blue light-activated stomatal response in a phot1
      phot2 double mutant. The 14-3-3 lambda mutant in the phot1 mutant background
      allowed normal phototropism and normal chloroplast accumulation and avoidance
      responses. It also showed normal stomatal opening mediated by PHOT1 in a phot2
      mutant background. The 14-3-3 kappa mutant had no effect on stomatal opening in
      response to blue light. Although the 14-3-3 lambda mutant had no chloroplast
      movement phenotype, the 14-3-3 kappa mutation caused a weaker avoidance response
      at an intermediate blue light intensity by altering the balance between the
      avoidance and accumulation responses. The results highlight the strict
      specificity of phototropin-mediated signal transduction pathways.

PMID- 22408080
TI  - Combined loss of cRel/p50 subunits of NF-kappaB leads to impaired innate host
      response in sepsis.
AB  - NF-kappaB, which comprises homo- and hetero-dimers of the five members of the Rel
      family, plays a crucial role in immunity to infection. The cRel and p50 subunits
      have been implicated in the development and function of the immune cells, but
      their in vivo importance remains poorly explored in sepsis. We aimed to study the
      impact of the combined loss of these two subunits on the innate response to
      infection in a cecal ligation and puncture model of sepsis. We have explored the
      possible defects in host defense, including pathogen clearance, bacterial
      phagocytosis and cytokine plasma release. We also performed gene profiling of
      cRel(-/-)p50(-/-) and wild-type LPS-stimulated peritoneal macrophages. Deficiency
      of cRel and p50 led to enhanced mortality to sepsis that was associated with
      defective macrophages phagocytosis, decreased bacterial clearance and moderate
      cytokine response. Transcription profile analysis revealed a common inflammatory
      response but a significant down-regulated transcription of genes encoding for
      pathogen recognition receptors and antimicrobial molecules, supporting the in
      vivo findings in mice. In conclusion, the cRel and p50 subunits of NF-kappaB play
      an important combined role in the innate response and are crucial for survival
      and pathogen clearance in polymicrobial sepsis.

PMID- 22408081
TI  - Effect of biological/physical stimulation on guided bone regeneration through
      asymmetrically porous membrane.
AB  - Asymmetrically porous polycaprolactone (PCL)/Pluronic F127 guided bone
      regeneration (GBR) membranes were fabricated. The top surface of the membrane had
      nanosize pores (~10 nm) which can effectively prevent invasion by fibrous
      connective tissue but permeate nutrients, whereas the bottom surface had
      microsize pores (~200 MUm) which can enhance the adhesiveness with bone tissue.
      Ultrasound was applied to a bone morphogenetic protein (BMP-2)-immobilized
      PCL/F127 GBR membrane to investigate the feasibility of using dual biological
      (BMP-2) and physical (ultrasound) stimulation for enhancing bone regeneration
      through the membrane. In an animal study using SD rats (cranial defect model),
      the bone regeneration behavior that occurred when using BMP-2-loaded GBR
      membranes with ultrasound treatment (GBR/BMP-2/US) was much faster than when the
      same GBR membrane was used without the ultrasound treatment (GBR/BMP-2), as well
      as when GBR membranes were used without stimulations (GBR). The enhanced bone
      regeneration of the GBR/BMP-2/US group can be interpreted as resulting from the
      synergistic or additive effect of the asymmetrically porous PCL/F127 membrane
      with unique properties (selective permeability, hydrophilicity, and
      osteoconductivity) and the stimulatory effects of BMP-2 and ultrasound
      (osteoinductivity). The asymmetrically porous GBR membrane with dual BMP-2 and
      ultrasound stimulation may be promising for the clinical treatment of delayed and
      insufficient bone healing.

PMID- 22408083
TI  - Technical note: Evaluation of bimodal distribution models to determine meal
      criterion in heifers fed a high-grain diet.
AB  - Meals are clusters of feedbunk visit (BV) events that are differentiated from the
      next meal by a nonfeeding interval that is longer compared with the nonfeeding
      intervals within a meal. The longest nonfeeding interval considered to be part of
      a meal is defined as the meal criterion. The objective of this study was to
      determine which combination of 2 probability density functions [(PDF): Gaussian
      normal (G), Weibull (W), Log-Normal, Gamma, and Gumbel] used in a bimodal
      distribution model had the best fit of nonfeeding interval data collected in beef
      heifers. Feeding behavior traits (572,627 total BV events) were measured in 119
      heifers fed a high-grain diet (3.08 Mcal ME/kg DM), using a GrowSafe system for
      66 d. The frequency and duration of BV events averaged 75 +/- 15 events/d and
      73.0 +/- 22.3 min/d, respectively. The bimodal PDF combinations were fitted to
      the log(10)-transformed interval lengths between BV events for each animal, using
      R mixdist package (2.13). The Akaike Information Criterion (AIC) was used to
      assess goodness of fit of the 25 bimodal PDF combinations. The PDF model with the
      least AIC value was selected as the best fit for each individual. A chi(2)
      analysis of the selected best PDF distribution across individuals revealed that
      78.2% of the heifers best fit were G-W or W-W PDF models. The likelihood
      probability estimates were calculated from the average AIC deviation of each
      model from the standard G-G model. The G-W likelihood probability estimate was
      greater (P = 0.001) than the W-W combination (0.997 vs. 0.727). Our analysis
      indicated the G-W model had a statistically better fit and is most likely the
      best approach to define meal criterion in beef heifers fed high-grain diets.

PMID- 22408082
TI  - Experiences of non-UK-qualified doctors working within the UK regulatory
      framework: a qualitative study.
AB  - OBJECTIVE: To explore the experience of non-UK-qualified doctors in working
      within the regulatory framework of the General Medical Council (GMC) document
      Good Medical Practice. DESIGN: Individual interviews and focus groups. SETTING:
      United Kingdom. PARTICIPANTS: Non-UK-qualified doctors who had registered with
      the GMC between 1 April 2006 and 31 March 2008, doctors attending
      training/induction programmes for non-UK-qualified doctors, and key informants
      involved in training and support for non-UK-qualified doctors. MAIN OUTCOME
      MEASURES: Themes identified from analysis of interview and focus group
      transcripts. RESULTS: Information and support for non-UK qualified doctors who
      apply to register to work in the UK has little reference to the ethical and
      professional standards required of doctors working in the UK. Recognition of the
      ethical, legal and cultural context of UK healthcare occurs once doctors are
      working in practice. Non-UK qualified doctors reported clear differences in the
      ethical and legal framework for practising medicine between the UK and their
      country of qualification, particularly in the model of the doctor-patient
      relationship. The degree of support for non-UK-qualified doctors in dealing with
      ethical concerns is related to the type of post they work in. European doctors
      describe similar difficulties with working in an unfamiliar regulatory framework
      to their non-European colleagues. CONCLUSIONS: Non-UK-qualified doctors
      experience a number of difficulties related to practising within a different
      ethical and professional regulatory framework. Provision of information and
      educational resources before registration, together with in-practice support
      would help to develop a more effective understanding of GMP and its implications
      for practice in the UK.

PMID- 22408084
TI  - Technical note: Can the sulfur hexafluoride tracer gas technique be used to
      accurately measure enteric methane production from ruminally cannulated cattle?
AB  - An experiment was conducted to determine whether using ruminally cannulated
      cattle affects the estimate of enteric methane (CH(4)) emissions when using the
      sulfur hexafluoride (SF(6)) tracer technique with samples taken from a head
      canister. Eleven beef cattle were surgically fitted with several types of ruminal
      cannula (2C, 3C, 3C+washer, 9C; Bar Diamond, Parma, ID). The 2C and 3C models
      (outer and inner flanges with opposite curvature) had medium to high leakage,
      whereas the 9C models (outer and inner flanges with the same curvature) provided
      minimum to moderate leakage of gas. A total of 48 cow-day measurements were
      conducted. For each animal, a permeation tube containing sulfur hexafluoride
      (SF(6)) was placed in the rumen, and a sample of air from around the nose and
      mouth was drawn through tubing into an evacuated canister (head canister). A
      second sample of air was collected from outside the rumen near the cannula into
      another canister (cannula canister). Background concentrations were also
      monitored. The methane (CH(4)) emission was estimated from the daily CH(4) and
      SF(6) concentrations in the head canister (uncorrected). The permeation SF(6)
      release rate was then partitioned based on the proportion of the SF(6)
      concentration measured in the head vs. the cannula canister. The CH(4) emissions
      at each site were calculated using the two release rates and the two CH(4):SF(6)
      concentration ratios. The head and cannula emissions were summed to obtain the
      total emission (corrected). The difference (corrected - uncorrected) in CH4
      emission was attributed to the differences in CH(4):SF(6) ratio at the 2 exit
      locations. The proportions of CH(4) and SF(6) recovered at the head were greater
      (P < 0.001) for the 9C cannulas (64% and 66%) compared with the other cannulas,
      which were similar (P > 0.05; 2C, 6% and 4%; 3C, 17% and 15%; 3C+washer, 19% and
      14%). Uncorrected CH(4) emissions were +/- 10% of corrected emissions for 53% of
      the cow-day measurements. Only when more than 80% of the SF(6) escaped via the
      rumen did the difference between the uncorrected and corrected CH(4) emissions
      exceed 20%. We concluded that using cannulated cattle introduces more variability
      into the SF(6) technique used with a head canister, a technique that is already
      highly variable. Thus, use of cannulated animals is not recommended when using
      the SF(6) technique with head canister. However, if cannulated cattle are used,
      the cannulas need to be tight-fitting to minimize leakage, and large animal
      numbers are needed to overcome the additional variability.

PMID- 22408085
TI  - Effects of housing and feeding systems on performance of neonatal Holstein bull
      calves.
AB  - As the dairy industry continues to grow, more dairy calves are available for
      dairy, beef, and veal purposes. Rearing systems must be highly efficient to make
      this industry cost efficient, making the evaluation of rearing methods important
      to establish the most practical method. A study was designed and conducted to
      evaluate effects of housing and feeding systems on performance of neonatal
      Holstein bull calves. Treatments (2 * 2 factorial arrangement) consisted of: 1)
      individually housed, bottle-fed (n = 5 bull calves); 2) individually housed,
      bucket-fed (n = 5 bull calves); 3) group-housed, bottle-fed (n = 5 pens; 4 bull
      calves/pen); and 4) group-housed, bucket- (trough) fed (n = 5 pens; 3 or 4 bull
      calves/pen). Feeding treatments began on d 7 when calves had been acclimated to
      their new environment. Body weight measurements were collected every 7 d and
      blood samples were collected on d 0, 28, 55, and 66 for beta-hydroxybutyrate
      (BHBA) concentration as a gross indicator of ruminal development. No housing *
      feeding interactions or feeding treatment effects were observed (P > 0.10).
      Average DMI (dry feed plus milk replacer) was increased (P < 0.05) for group
      housed vs. individual animals after d 41, and final BW was greater (P < 0.05) for
      group-housed calves compared with individually housed calves. Feed efficiency and
      ADG, however, remained similar (P > 0.10) for all treatments. Fecal scores (P >
      0.26), CV for BW (P > 0.26), and BHBA concentrations (P > 0.14) showed no
      differences among treatments. Housing system had greater effect on calf
      performance compared with milk feeding regimen.

PMID- 22408086
TI  - Ruminal acidosis challenge impact on ruminal temperature in feedlot cattle.
AB  - The objective of this experiment was to determine if ruminal temperature rise
      coincides with pH reduction using an acidosis challenge model. Twelve ruminally
      cannulated steers (518 +/- 28 kg BW) were administered ruminal temperature
      monitoring devices that recorded temperature every 2 min. Steers were fed a 63%
      concentrate diet at 1.6% BW for 20 d before being randomly assigned to 1 of 3
      acidosis challenge treatments: no dietary change (CON), one-half of daily DMI
      replaced with cracked corn (HALF), or all of daily DMI replaced with cracked corn
      (CORN). The challenge was initiated by ruminally dosing steers with their
      treatment diets. Ruminal pH and rectal temperatures (T(rec)) were recorded every
      3 h for 72 h. All steers were offered CON diets at 24 and 48 h after challenge.
      Ruminal pH showed a treatment * day effect (P = 0.01). Ruminal pH of CORN steers
      was lower (P = 0.03) than that of HALF steers on d 1, was lower (P <= 0.004) than
      that of HALF and CON steers on d 2, and tended to be lower (P <= 0.10) than that
      of HALF and CON steers on d 3. Treatment did not affect (P >= 0.42) RecT. Ruminal
      temperature (T(rum)) showed a treatment . d(-1) . h(-1) after feeding interaction
      (P < 0.01). At 3 h after challenge, T(rum) of CORN and HALF steers was higher (P
      <= 0.01) than that of CON steers. On d 2, T(rum) of CORN steers was higher (P <=
      0.03) than that of CON between 6 and 12 h after feeding. From 15 to 21 h after
      feeding on d 2, T(rum) of HALF steers was higher (P < 0.01) than that of CORN and
      CON steers. On d 3, at the time of feeding until 3 h later, T(rum) of CORN steers
      was lower (P <= 0.04) than that of all other steers. Rectal temperature was
      correlated (P <= 0.01) with T(rum) on all days for CON and CORN steers. Ruminal
      pH was negatively correlated (P <= 0.04) with T(rec) on d 2 and T(rum) on d 1 in
      CORN steers, and T(rum) was negatively correlated (P <= 0.02) with ruminal pH in
      HALF and CON steers on d 1 and 3, respectively. The amount of time above T(rum)
      of 39.0 degrees C or 39.45 degrees C was correlated (P <= 0.05) with the time
      spent below a ruminal pH of 5.5 in CORN steers; however, time above T(rum) of
      39.0 degrees C did not differ (P = 0.87) among treatments. Results indicate that
      there is a negative relationship between T(rum) and ruminal pH during an acidotic
      episode; therefore, T(rum) monitoring can detect a potential acidotic episode.

PMID- 22408087
TI  - Effects of different fresh-cut forages and their hays on feed intake,
      digestibility, heat production, and ruminal methane emission by Boer x Spanish
      goats.
AB  - Twenty-four yearling Boer * Spanish wethers were used to assess effects of
      different forages, either fresh (Exp. 1) or as hay (Exp. 2), on feed intake,
      digestibilities, heat production, and ruminal methane emission. Treatments were:
      1) Sericea lespedeza (SER; Lespedeza cuneata), a legume high in condensed tannins
      (CT; 20% and 15% in fresh forage and hay, respectively), 2) SER supplemented with
      polyethylene glycol (SER-PEG; 25 g/d), 3) alfalfa (Medicago sativa), a legume low
      in CT (ALF), and 4) sorghum-sudangrass (Sorghum bicolor), a grass low in CT
      (GRASS). Experiments were 22 d, which included 16 d for acclimatization followed
      by a 6-d period for fecal and urine collection, and gas exchange measurement
      (last 2 d). Intake of OM was 867, 823, 694, and 691 g/d (SEM = 20.1) with fresh
      forage, and 806, 887, 681, and 607 g/d with hay for SER, SER-PEG, ALF, and GRASS,
      respectively (SEM = 46.6). Apparent total tract N digestion was greater for SER
      PEG vs. SER (P < 0.001) with fresh forage (46.3%, 66.5%, 81.7%, and 73.2%; SEM =
      1.71) and hay (49.7%, 71.4%, 65.4%, and 54.8% for SER, SER-PEG, ALF, and GRASS,
      respectively; SEM = 1.57). Intake of ME was similar among treatments with fresh
      forage (8.24, 8.06, 7.42, and 7.70 MJ/d; SEM = 0.434) and with hay was greater
      for SER-PEG than ALF (P < 0.03) and GRASS (P < 0.001) (8.63, 10.40, 8.15, and
      6.74 MJ/d for SER, SER-PEG, ALF, and GRASS, respectively; SEM = 0.655). The
      number of ciliate protozoa in ruminal fluid was least for SER with fresh forage
      (P < 0.01) (9.8, 20.1, 21.0, and 33.6 * 10(5)/ml; SEM = 2.76) and hay (P < 0.02)
      (6.3, 11.4, 13.6, and 12.5 * 10(5)/ml for SER, SER-PEG, ALF, and GRASS,
      respectively; SEM = 1.43). Methane emission as a percentage of DE intake was
      lower (P < 0.01) for SER vs. ALF and GRASS with fresh forage (6.6, 8.3, 9.4, and
      9.2%; SEM = 0.64) and hay (4.3, 4.9, 6.4, and 6.7% for SER, SER-PEG, ALF, and
      GRASS, respectively; SEM = 0.38). In summary, methane emission in this short-term
      experiment was similar between a legume and grass low in CT as fresh forage and
      hay. The CT in SER markedly decreased N digestibility and elicited a moderate
      decline in ruminal methane emission. Supplementation with PEG alleviated the
      effect of CT on N digestibility but not ruminal methane emission, presumably
      because of different modes of action. In conclusion, potential of using CT
      containing forage as a means of decreasing ruminal methane emission requires
      further study, such as with longer feeding periods.

PMID- 22408088
TI  - Evaluation of Columbia, USMARC-Composite, Suffolk, and Texel rams as terminal
      sires in an extensive rangeland production system: III. Prefabrication carcass
      traits and organ weights.
AB  - To evaluate terminal-sire breeds, harvest BW, prefabrication carcass
      measurements, and organ weights were evaluated over 3 yr for 518 crossbred wether
      lambs (ovis aries). Lambs were produced by single-sire matings of 22 Columbia, 22
      USMARC-Composite (Composite), 21 Suffolk, and 17 Texel rams to adult Rambouillet
      ewes. Lambs were raised to weaning under an extensive western rangeland
      production system and finished in a feedlot on a high-energy finishing diet.
      Wethers were randomly assigned to be harvested at an average BW of 54.4, 61.2, or
      68.0 kg and then transported to The Ohio State University abattoir for harvest.
      Wether BW was recorded before transport (off-test BW) and before harvest.
      Prefabrication carcass measurements and organ weights were recorded either after
      harvest or after an approximate 24-h chill. At comparable numbers of days on
      feed, Suffolk-sired lambs had heavier (P < 0.01) off-test BW, harvest BW, HCW,
      chilled carcass weight (CCW), and kidney weights than lambs sired by the other
      breeds. Suffolk-sired lambs had more (P < 0.01) kidney-pelvic fat than did
      Columbia-sired lambs; Composite- and Texel-sired lambs were intermediate and did
      not differ (P > 0.06) from the other crossbred lambs. Texel- and suffolk-sired
      lambs had larger lm area and greater conformation scores than Columbia-sired
      lambs (P < 0.03). Texel-sired lambs had greater (P < 0.01) body wall thickness,
      quality grades, and leg scores than Columbia-sired lambs. Composite- and Suffolk
      sired lambs did not differ from each other or from lambs sired by any other breed
      for body wall thickness (P > 0.18) and were intermediate for quality grades and
      leg scores. Sire breed did not affect (P > 0.05) shipping shrink, dressing
      percentage, pelt weight, liver weight, and fat depth. Adjusting data to a
      comparable off-test BW or CCW modified sire breed rankings for some measurements.
      Texel-sired lambs were equal or superior to lambs sired by other breeds for HCW,
      CCW, dressing percentage, pelt weight, LM area, quality grade, and leg and
      conformation scores. However, Texel-sired lambs also had values for kidney-pelvic
      fat weight, fat depth, and body wall thickness that were equal to or greater than
      those of lambs sired by the other breeds, indicating increased fatness at
      comparable BW. Producers can use these results to select terminal-sire sheep
      breeds that will complement their production system and improve market lamb
      value.

PMID- 22408089
TI  - Y are you not pregnant: identification of Y chromosome segments in female cattle
      with decreased reproductive efficiency.
AB  - Reproductive efficiency is of economic importance in commercial beef cattle
      production, since failure to achieve pregnancy reduces the number of calves
      marketed. Identification of genetic markers with predictive merit for
      reproductive success would facilitate early selection of females and avoid
      inefficiencies associated with sub-fertile cows. To identify regions of the
      genome harboring variation affecting reproductive success, we applied a genome
      wide association approach based on the >700,000 SNP marker assay. To include the
      largest number of individuals possible under the available budget, cows from
      several populations were assigned to extremes for reproductive efficiency, and
      DNA was pooled within population and phenotype before genotyping. Surprisingly,
      pools prepared from DNA of low reproductive cattle returned fluorescence
      intensity data intermediate between fertile females and males for SNP mapped to
      the Y chromosome (i.e., male sex chromosome). The presence of Y-associated
      material in low reproductive heifers or cows was confirmed by Y-directed PCR,
      which revealed that 21 to 29% of females in the low reproductive category were
      positive by a Y chromosome PCR test normally used to sex embryos. The presence of
      the Y chromosome anomaly was further confirmed with application of additional Y
      specific PCR amplicons, indicating the likelihood of the presence of some portion
      of male sex chromosome in female cattle in various beef cattle herds across the
      U.S. Discovery of this Y anomaly in low reproductive females may make an
      important contribution to management of reproductive failures in beef cattle
      operations.

PMID- 22408090
TI  - Evaluation of Columbia, USMARC-Composite, Suffolk, and Texel rams as terminal
      sires in an extensive rangeland production system: II. Postweaning growth and
      ultrasonic measures of composition for lambs fed a high-energy feedlot diet.
AB  - Over 3 yr, postweaning growth patterns and changes in ultrasonic measurements of
      fat depth (FD) and LM area were assessed for 1,049 crossbred ewe and wether lambs
      (Ovis aries) produced by mating adult Rambouillet ewes to 1 of 22 Columbia, 22
      USMARC-Composite (Composite), 21 Suffolk, or 17 Texel rams and raised to weaning
      under extensive Western rangeland conditions. After weaning, lambs were
      transitioned to a high-energy finishing diet in a feedlot, weighed weekly for 13
      to 16 wk, and scanned using ultrasound at 2-wk intervals to estimate FD and LM
      area between the 12th and 13th ribs. Lambs sired by Suffolk rams were 5 to 12%
      heavier (P < 0.05) at start of test, grew 14 to 22% faster (P < 0.001), and were
      correspondingly 7 to 14% heavier (P < 0.001) after 90 d on test than lambs sired
      by rams of the other 3 breeds. At this time, lambs sired by Texel rams were 5%
      lighter (P < 0.01) than Columbia- or Composite-sired lambs, which did not differ
      (P > 0.20). Columbia-sired lambs had less FD (8.9 mm) but smaller LM areas (15.6
      cm(2)) at 90 d on test (both P < 0.01) than lambs sired by rams of the other
      breeds (average of 9.8 mm for FD and 16.6 cm(2) for LM area), which did not
      differ for either measurement at this time. At 60 kg, predicted FD differed among
      sire breeds (P < 0.001) and were similar for Suffolk- (7.6 mm) and Columbia-sired
      (7.9 mm) lambs, intermediate for Composite-sired lambs (9.1 mm), and largest for
      Texel-sired (10.1 mm) lambs. At a BW of 60 kg, LM area differed between all pairs
      of sire breeds (P < 0.05), and was largest for Texel-sired lambs (16.7 cm(2)),
      followed by Composite-, Suffolk-, and Columbia-sired lambs (15.7, 14.8, and 14.5
      cm(2), respectively). At a predicted FD of 9.1 mm (the boundary between U.S.
      Yield Grades 3 and 4), the predicted LM area for Suffolk-sired lambs (16.2 cm(2))
      was similar (P > 0.10) to that of Texel-sired lambs (16.0 cm(2)) and superior (P
      < 0.01) to that of Composite- (15.7 cm(2)) and Columbia-sired lambs (15.4 cm(2)).
      Lambs sired by Suffolk rams were thus equal or superior to lambs sired by the
      other 3 breeds in growth, FD, and LM area at comparable ages, fatness at 60 kg,
      and LM area at a FD of 9.1 mm, but inferior in LM area to Texel- and Composite
      sired lambs at comparable BW.

PMID- 22408092
TI  - Government to pursue a ban on wild animals in circuses.

PMID- 22408093
TI  - BVA calls for further review of pedigree breed standards.

PMID- 22408091
TI  - Dissecting phosphite-induced priming in Arabidopsis infected with
      Hyaloperonospora arabidopsidis.
AB  - Phosphite (Phi), a phloem-mobile oxyanion of phosphorous acid (H(3)PO(3)),
      protects plants against diseases caused by oomycetes. Its mode of action is
      unclear, as evidence indicates both direct antibiotic effects on pathogens as
      well as inhibition through enhanced plant defense responses, and its target(s) in
      the plants is unknown. Here, we demonstrate that the biotrophic oomycete
      Hyaloperonospora arabidopsidis (Hpa) exhibits an unusual biphasic dose-dependent
      response to Phi after inoculation of Arabidopsis (Arabidopsis thaliana), with
      characteristics of indirect activity at low doses (10 mm or less) and direct
      inhibition at high doses (50 mm or greater). The effect of low doses of Phi on
      Hpa infection was nullified in salicylic acid (SA)-defective plants (sid2-1,
      NahG) and in a mutant impaired in SA signaling (npr1-1). Compromised jasmonate
      (jar1-1) and ethylene (ein2-1) signaling or abscisic acid (aba1-5) biosynthesis,
      reactive oxygen generation (atrbohD), or accumulation of the phytoalexins
      camalexin (pad3-1) and scopoletin (f6'h1-1) did not affect Phi activity. Low
      doses of Phi primed the accumulation of SA and Pathogenesis-Related protein1
      transcripts and mobilized two essential components of basal resistance, Enhanced
      Disease Susceptibility1 and Phytoalexin Deficient4, following pathogen challenge.
      Compared with inoculated, Phi-untreated plants, the gene expression,
      accumulation, and phosphorylation of the mitogen-activated protein kinase MPK4, a
      negative regulator of SA-dependent defenses, were reduced in plants treated with
      low doses of Phi. We propose that Phi negatively regulates MPK4, thus priming SA
      dependent defense responses following Hpa infection.

PMID- 22408095
TI  - Scenarios for the future spread of Schmallenberg virus.

PMID- 22408098
TI  - New alliance to set standards for drugs to treat trypanosomosis.

PMID- 22408099
TI  - Disciplinary case dismissed.

PMID- 22408101
TI  - PRRSV and PCV-2-associated disease cause wasting in pigs.

PMID- 22408102
TI  - From inns and coffee houses to Red Lion Square.

PMID- 22408103
TI  - Is Q fever a significant cause of reproductive failure in cattle?

PMID- 22408104
TI  - Unusual antebrachial pathology in skeletally immature pugs.

PMID- 22408105
TI  - Modernising meat inspection.

PMID- 22408106
TI  - Farm assurance schemes and animal welfare.

PMID- 22408107
TI  - Slaughtering lambs without stunning.

PMID- 22408108
TI  - Supporting the veterinary benevolent fund.

PMID- 22408109
TI  - Identifying an immune signature against invasive Salmonella.

PMID- 22408110
TI  - An accessible method for teaching doctors about death certification.
AB  - The World Health Organization (WHO) recommends that data on mortality in its
      member countries are collected utilising the Medical Certificate of Cause of
      Death published in the instruction volume of the ICD-10. However, investment in
      health information processes necessary to promote the use of this certificate and
      improve mortality information is lacking in many countries. An appeal for support
      to make improvements has been launched through the Health Metrics Network's MOVE
      IT strategy (Monitoring of Vital Events Information Technology) (WHO 2011).
      Despite this international spotlight on the need for capture of mortality data
      and in the use of the ICD-10 to code the data reported on such certificates,
      there is little cohesion in the way that certifiers of deaths receive instruction
      in how to complete the death certificate, which is the main source document for
      mortality statistics. Complete and accurate documentation of the immediate,
      underlying and contributory causes of death of the decedent on the death
      certificate is a requirement to produce standardised statistical information and
      to the ability to produce cause-specific mortality statistics that can be
      compared between populations and across time. This paper reports on a research
      project conducted to determine the efficacy and accessibility of the
      certification module of the WHO's newly-developed web based training tool for
      coders and certifiers of deaths. Involving a population of medical students from
      the Fiji School of Medicine and a pre- and post-research design, the study
      entailed completion of death certificates based on vignettes before and after
      access to the training tool. The ability of the participants to complete the
      death certificates and analysis of the completeness and specificity of the ICD-10
      coding of the reported causes of death were used to measure the effect of the
      students' learning from the training tool. The quality of death certificate
      completion was assessed using a Quality Index before and after the participants
      accessed the training tool. In addition, the views of the participants about
      accessibility and use of the training tool were elicited using a supplementary
      questionnaire. The results of the study demonstrated improvement in the ability
      of the participants to complete death certificates completely and accurately
      according to best practice. The training tool was viewed very positively and its
      implementation in the curriculum for medical students was encouraged.
      Participants also recommended that interactive discussions to examine the
      certification exercises would be an advantage.

PMID- 22408111
TI  - A study of the difference in volume of information in chief complaint and present
      illness between electronic and paper medical records.
AB  - The introduction of an electronic medical record (EMR) has been rapidly
      accelerating in South Korea. The EMR was expected to improve quality of care,
      readability, availability, and the quality of data. However, the reluctance of
      healthcare providers to use the EMR may have caused a reduction of information
      recorded in EMRs. The purpose of this study was to identify whether there was any
      loss of information following the introduction of a narrative text-based EMR in
      the recording of chief complaint and present illness in inpatient medical
      records. Inpatient medical records of a university hospital were retrospectively
      evaluated for one month before and one month after the introduction of the EMR in
      June 2006. The volume of information for chief complaint and present illness was
      measured by number of words in Korean and normalised bytes. Change in volume of
      information was measured by two-way ANOVA and multiple regression analyses,
      controlling for doctors' gender, age, and grade/year of residents, patients'
      readmission status, reasons for admission and service department to assess any
      effect of the introduction of an EMR. Total numbers of paper-based medical
      records (PMRs) and EMRs for analysis were 1,159 and 1,122, respectively. Forty
      three doctors participated in the study. Thirty-one (72%) doctors were less than
      30 years of age. Number of words proved a better outcome measure (R2=22 for CC,
      R2=36 for PI) than normalised bytes (R2=18 for CC, R2=35 for PI) for measuring
      volume of information. Results showed that the volume of information in the chief
      complaint and present illness was not decreased after the introduction of the
      EMR, except when the dependent variable was measured by number of words in the
      present illness. The study showed that the introduction of the EMR did not reduce
      the volume of information documented for chief complaint and present illness in
      inpatient medical records. However, further studies are needed to identify how to
      control the probable loss of information as showed in present illness measured by
      number of words.

PMID- 22408112
TI  - Deploying information technology and continuous control monitoring systems in
      hospitals to prevent medication errors.
AB  - The serious repercussions of healthcare errors on patient safety have led
      hospitals to deploy information technology and continuous control monitoring
      systems to prevent them. Hospitals are moving away from traditional paper-based
      systems and focusing on designing new systems that prevent errors, using
      information technologies to catalyse the process re-engineering. This paper
      presents a case study that analyses the effect of computerised physician order
      entry and automated unit-based medication storage and distribution systems on the
      drug ordering and delivery process. It is concluded that information technology
      and continuous control monitoring systems have led to significant process re
      engineering in the sequential stages of the drug ordering and delivery system.
      The new systems have also provided the opportunity to improve information
      available. This is an exploratory case study and the conclusions drawn from it
      offer possible routes for future research in this field.

PMID- 22408113
TI  - The opioid dependent mother and newborn- an update. The 6th Annual Ivey
      Symposium.
AB  - The sixth Ivey Chair Symposium, held at the University of Western Ontario in
      October 2011, was dedicated to an update on the complex issues surrounding opioid
      dependent mothers and their newborns. The day commenced with Loretta Finnegan who
      provided a historical overview of the complex issues surrounding the addicted
      mother and her baby suffering from neonatal withdrawal syndrome. It is remarkable
      that the tool devised by Dr Finnegan forty years ago is in wide use today,
      capturing accurately the severity of NAS and the need for follow up and
      treatment. She stressed that comprehensive approach to the care of pregnant drug
      dependent mothers and their babies significantly reduces maternal and infant's
      morbidity. The risk of low birth weight and severe withdrawal can be reduced
      substantially when both patients in this dyad are optimally cared for. The seven
      speakers following her provided an update on the medicinal and non drug approach
      to treat the opioid-dependent mother and her newborn, including new Canadian
      guidelines which were just released. 

PMID- 22408114
TI  - Familial occurrence of Caffey-Silverman syndrome.
AB  - Caffey-Silverman syndrome, or infantile hyperostosis, is a rare condition of
      unclear etiology and pathogenesis affecting the skeletal system and the
      surrounding soft tissues. It is characterized by indurated swelling of soft
      tissues and cortical bone hyperostosis. The changes are usually multiple and
      affect such parts as the mandible, scapulae, ribs, clavicles, and forearm and
      shank bones. When long bones are affected, the lesions are typically limited to
      shafts, with the sparing of meta- and epiphyses. The prognosis is usually good
      and, in most patients, the changes resolve spontaneously after several months to
      over a year, leaving no permanent sequelae. Caffey-Silverman syndrome needs to be
      distinguished from osteitis, for which it is most often mistaken.  We present a
      case of an early form of Caffey-Silverman syndrome. The course of disease in this
      form is usually severe, with multifocal lesions, and the typical self-limiting
      regression is not complete. In our patient, a systemic musculoskeletal condition
      was already suspected following the detection of skeletal defects in a prenatal
      US examination.  Physical and radiological work-up in the first weeks of life
      revealed the typical signs of congenital Caffey-Silverman syndrome. Several years
      of follow-up showed gradual regression of the bone deformities with persistent
      lower-extremity bowing. Due to a positive family history for Caffey-Silverman
      syndrome, the patient's pedigree was prepared. On the basis of the history data,
      existing radiographs and in- and outpatient medical records, Caffey-Silverman
      syndrome was confirmed in 10 family members. It was established that the cases of
      Caffey-Silverman syndrome in the patient's family were characterized by diverse
      phenotypic expression and different times of onset.

PMID- 22408115
TI  - Social isolation associated with depression: a case report of hikikomori.
AB  - BACKGROUND: Social isolation is associated with significant morbidity and
      mortality. A severe form of social isolation or social withdrawal, called
      hikikomori in Japan, has been described, but controversy over the etiology and
      universality of the phenomenon remains. METHOD: Case report. RESULTS: Diagnostic
      assessment by structured clinical interview and psychometric tools revealed
      hikikomori and underlying bipolar disorder, in which the patient's social
      withdrawal occurred exclusively during major depressive episodes. The patient
      declined pharmacotherapy, but his hikikomori and depression went into remission
      after 25 sessions of cognitive behavioural therapy targeting his social
      isolation. CONCLUSIONS: This is the first reported case of hikikomori in the
      Americas. It illustrates the association between hikikomori and a mood disorder,
      and suggests the importance of international study of the prevalence and
      potential treatment strategies for severe social isolation.

PMID- 22408116
TI  - Religiousness, religious coping methods and distress level among psychiatric
      patients in Malaysia.
AB  - BACKGROUND: Patients having psychiatric diagnoses often experience high level of
      distress. Religiousness is often used by them as part of their coping mechanism
      and problem-solving strategies. OBJECTIVE: To determine the level of religious
      commitment and coping methods in psychiatric patients and its relationship with
      distress level. METHODS: Religious commitment and coping patterns were measured
      with the Duke University Religious Index (DUREL) and Brief RCOPE, respectively.
      Psychopathology was assessed using the Brief Psychiatric Rating Scale (BPRS) and
      distress level was assessed with the Depressive, Anxiety and Stress Scale (DASS).
      Social support and experiences of recent threatening events were measured with
      the Multidimensional Scale of Perceived Social Support (MSPSS) and Life
      Threatening Events (LTE). RESULTS: A total of 228 patients were included in this
      study with a mean age of 40.2 years. The majority were male, Malay, Muslim,
      single and with psychotic disorder. The subjects had a high level of religious
      commitment and had used more positive coping methods. Negative religious coping,
      psychiatric symptoms and diagnosis of anxiety disorder or major depression were
      significantly associated with high distress level. Higher religious commitment
      was significantly associated with lower distress (p < .05). CONCLUSION:
      Psychiatric patients were religiously committed and used more positive religious
      coping methods. Practices of negative religious coping, severe psychiatric
      symptoms and anxiety/depression were associated with higher distress.

PMID- 22408117
TI  - Parameters of education and the course of depression: an analysis in the Turkish
      sociocultural context.
AB  - BACKGROUND: Major depression (MD) is often marked by an unfavourable course.
      Education repeatedly was found to be associated with better mental health
      variables, but longitudinal data are scarce. This evaluation seeks to identify
      the predictive role of specific aspects of education on the course of depression
      in a socioculturally defined setting. METHODS: A sample of 69 unipolar MD
      outpatients in university and primary health care in Antalya, Turkey were
      observed naturalistically for a mean 11-month period. The baseline examination
      included several psychosocial variables, among them the highest attained
      schooling degree (DEG), possible further but unfulfilled educational aspirations
      (UEA), and the participants' parental educational level (PEL). The depressive
      symptomatology was assessed with the HAM-D-17 at baseline and at four-monthly
      follow-ups. A binary variable differentiated 'non-remissive' from 'remissive'
      courses, the latter displaying at least temporal partial remissions. RESULTS:
      Forty-two per cent of the sample displayed a non-remissive one-year course of MD.
      Half of the participants reported UEA. This was more prevalent among women, and
      qualitative information added causal gender-specific perceptions. In logistic
      regression, DEG proved prognostic impact, but was exceeded by the combination of
      UEA and PEL as the strongest predictor model (Cox & Snell R(2) = 0.217). This
      remained when controlled for place of examination, gender and initial severity of
      depression. As risk factors for low education, a pattern of female gender and
      large family size (itself predicted by rural descent) emerged. CONCLUSIONS: Low
      education proved to be a risk factor for an unfavourable course of MD. Not only
      actual experienced schooling, but also unfulfilled academic aspirations and a low
      parental educational level appear to be of crucial impact.

PMID- 22408118
TI  - Mental illness among journalists: a systematic review.
AB  - BACKGROUND: Mass media depictions of people with mental illness have a strong
      influence on public attitudes, to the extent that changes in these depictions can
      reduce public stigmatization of people with such illness. Journalists' mental
      health may influence their depiction of those with mental illness, but little is
      known about this. AIMS: To investigate mental illness among journalists in five
      key areas: (1) journalists' mental health status; (2) journalists' personal
      attitudes towards mental illness; (3) attitudes and support journalists expect or
      have experienced from colleagues when they have a mental health problem; (4)
      effect of journalism's professional culture on the course of mental illness; and
      (5) effect of journalism's professional culture on mass media depictions of
      people with mental illness. METHODS: We performed a systematic screening of
      MEDLINE, PsycINFO, EMBASE, Web of Science and the Cochrane Library regarding the
      study aims. RESULTS: We identified 19, 12, seven and four studies for aims 1, 2,
      3, and 4, respectively. No articles were found for aim 5. CONCLUSIONS: The
      prevalence of post-traumatic stress disorder (PTSD) among journalists is higher
      than that among the general population. Journalists have positive personal
      attitudes towards mental illness, but there are perceived workplace disincentives
      to disclose mental health problems.

PMID- 22408119
TI  - Perceived human rights violation in persons with mental illness: role of
      education.
AB  - BACKGROUND: People with mental illness are vulnerable to human rights violations
      and people with illiteracy and mental illness are at a double disadvantage.
      OBJECTIVE: To determine the role of education in ascertaining human rights needs
      of people with mental illness. METHODOLOGY: This was a descriptive study carried
      out among randomly selected (N = 100) recovered psychiatric patients with mental
      illness in the past based on the Clinical Global Impression-Improvement scale at
      a tertiary care centre. Data were collected through face-to-face interview using
      structured needs assessment questionnaire comprising two sections related to
      family and community domains. Data were analysed and interpreted using
      descriptive and inferential statistics. FINDINGS: Our findings revealed that
      human rights needs in the physical needs dimension--i.e., access to electricity
      (chi2 = 5.523, p < .019) and safe drinking water facilities (chi2 = 9.665, p <
      .022)--were rated higher in illiterates than in literates. The human rights needs
      in emotional dimension - i.e. feeling separated from their families because of
      their illness (chi2 = 13.118, p < .004), afraid of family members (chi2 = 13.388,
      p < .004) and called filthy nicknames (chi2 = 17.759, p < .000) - were rated
      higher in literates than in illiterates. The human rights needs in the religious
      needs dimension - i.e. allowed to go to temple, church, mosque etc. (chi2 =
      12.000, p < .007) - and in the social needs dimension - i.e. friendliness with
      family members -were rated higher in illiterates than in literates (chi2 = 9.661,
      p < .022). CONCLUSION: Empowering people with mental illness by providing
      adequate opportunity to pursue education will play an important role in
      fulfilling the obligation of the United Nations Convention on the Rights of
      Persons with Disabilities.

PMID- 22408120
TI  - Depression risks in mothers of children with developmental disabilities: a cross
      cultural comparison of Brazil, Colombia, Malaysia and Thailand.
AB  - BACKGROUND: Compared with US or European countries, there are fewer mental health
      services for mothers of children with developmental disabilities in Latin
      American and/or Southeast Asian countries. AIMS: To explore the risk of
      depression in mothers of children with developmental disabilities in countries
      with a lack of mental health professionals, we conducted cross-cultural
      comparisons for four countries: Brazil, Colombia, Malaysia and Thailand. METHODS:
      Using the CES-D, we compared the participants' depressive symptoms, by which we
      also estimated the probability of morbid depression. RESULTS: In every country,
      participants tended to show depressive symptoms. In the CES-D total scores and
      the numbers of mothers who were observed to have a high level of depressive
      symptoms, there were significant differences among countries (F = 4.36, p = .006;
      chi2 = 10.3, p = .015). CONCLUSIONS: Considering cultural models, we could apply
      evidence-based intervention to depressive mothers of children, and conduct
      intervention and treatment for those mothers and evaluate ways of providing
      better mental health services to these individuals.

PMID- 22408121
TI  - Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric
      bypass: the pathophysiological role of GLP1 and its response to a somatostatin
      analogue.
AB  - BACKGROUND: Spontaneous hyperinsulinaemic hypoglycaemia following gastric bypass
      surgery (GBS) is increasingly recognised. However, its pathophysiology remains
      unclear. Some patients require pancreatectomy. Medical therapy with calcium
      channel blockers, acarbose and diazoxide has been reported to be beneficial but
      has variable adherence and response. METHOD: We demonstrate the role of GLP1,
      counter-regulatory hormones and the subsequent response of GLP1 to somatostatin
      analogue therapy in a 42-year-old woman with persistent neuroglycopaenia 6 years
      after GBS. Plasma GLP1, insulin and glucose were measured for 5  h on three
      settings: i) a 75  g oral glucose tolerance test (OGTT); ii) a standard liquid
      test meal (LTM); and iii) an OGTT 30  min after a s.c. injection of 100  MUg
      octreotide. RESULTS: In comparison with obese non-diabetic controls, the patient
      had an elevated fasting and a markedly enhanced GLP1 response during the OGTT,
      followed by an exaggerated insulin response and a subsequent low glucose level.
      The GLP1 response to a LTM was similar but greater. Octreotide given prior to the
      OGTT attenuated both the GLP1 and insulin responses and abolished hypoglycaemia.
      Octreotide therapy significantly improved the patient's neuroglycopaenic
      symptoms. The hormone profile was reassessed after 6 months following the LTM
      preceded by octreotide injection. Peak GLP1 and insulin responses were less
      pronounced than pretreatment responses and without hypoglycaemia. The patient was
      treated with lanreotide and had remained symptom-free and euglycaemic for 4
      years. CONCLUSION: An exaggerated incretin response following altered
      gastrointestinal anatomy was the likely cause of hypoglycaemia in our GBS
      patient. Somatostatin successfully suppressed this response acutely and in the
      long term, thereby avoiding pancreatectomy and its sequelae.

PMID- 22408122
TI  - Glucocorticoid treatment and impaired mood, memory and metabolism in people with
      diabetes: the Edinburgh Type 2 Diabetes Study.
AB  - OBJECTIVE: Both type 2 diabetes and glucocorticoid therapy are highly prevalent.
      Although people with type 2 diabetes may be more susceptible to adverse effects
      of glucocorticoids, and it is recommended that glucocorticoid therapy is avoided
      for fear of worsening glycaemic control, the extent to which this advice is
      followed and the consequences when glucocorticoids are prescribed are poorly
      documented. The aim was to assess the characteristics of people with type 2
      diabetes prescribed glucocorticoids in a real-world setting and to quantify
      resulting adverse effects. DESIGN: Cross-sectional cohort study. METHODS:
      Cardiometabolic variables, body fat distribution, cognitive function and mood
      were studied in the 1066 participants of the Edinburgh Type 2 Diabetes Study, of
      whom 162 (15%) were taking systemic, topical or inhaled glucocorticoids. RESULTS:
      Glucocorticoid therapy was more common in women and in smokers but was not
      avoided in patients with diabetic complications or cardiovascular risk factors.
      People taking glucocorticoids were more centrally obese with slightly higher
      HbA1c and total serum cholesterol but were no more likely to have hepatic
      steatosis or hypertension. Glucocorticoid treatment was associated with
      substantially lower mood and greater anxiety. Women taking glucocorticoid therapy
      were twice as likely to report depressive symptoms compared with those not taking
      treatment. Glucocorticoid therapy was also associated with poorer cognitive
      function among those with subclinical atherosclerosis, as indicated by low ankle
      brachial pressure index. CONCLUSIONS: Glucocorticoids are prescribed commonly for
      people with type 2 diabetes despite being associated with adverse indices of
      glycaemic control, cardiovascular risk factors, mood and cognitive function.

PMID- 22408123
TI  - GH activity and markers of inflammation: a crossover study in healthy volunteers
      treated with GH and a GH receptor antagonist.
AB  - INTRODUCTION: The GH/IGF1 axis may modulate inflammatory processes. However, the
      relationship seems complicated as both pro- and anti-inflammatory effects have
      been demonstrated. METHODS/DESIGN: Twelve healthy volunteers (mean age 36, range
      27-49 years) were treated in random order with increasing doses of GH for 3 weeks
      (first week 0.01  mg/kg per day, second week 0.02  mg/kg per day, and third week
      0.03  mg/kg per day) or a GH receptor antagonist (pegvisomant; first week 10 
      mg/day and last two weeks 15  mg/day), separated by 8 weeks of washout.
      Circulating levels of the pro-inflammatory cytokines tumor necrosis factor alpha
      (TNFalpha (TNFA)), interleukin 6 (IL6), and IL1beta (IL1B) and the acute phase
      proteins (APPs) C-reactive protein (CRP), haptoglobin, orosomucoid, YKL40
      (CHI3L1), and fibrinogen were measured. RESULTS: During GH treatment, IGF1
      (median 131 (Inter-quartile range (IQR) 112-166) vs 390 (322-524) MUg/l, P=0.002)
      increased together with TNFalpha (0.87 (0.74-1.48) vs 1.27 (0.80-1.69) ng/l,
      P=0.003), IL6 (1.00 (0.83-1.55) vs 1.35 (0.80-4.28) ng/l, P=0.045), and
      fibrinogen (9.2 (8.8-9.6) vs 11.1 (9.4-12.4) MUM, P=0.002). By contrast,
      orosomucoid decreased (18.0 (15.5-24.3) vs 15.0 (15.0-17.0) MUM, P=0.018). CRP,
      YKL40, and haptoglobin were unchanged. During pegvisomant treatment, IGF1
      decreased (139 (117-171) vs 91 (78-114) ng/ml, P=0.005). Orosomucoid (21.0 (16.3
      23.8) vs 22.0 (17.0-29.3) MUM, P=0.036) and CRP (1.00 (0.62-1.77) vs 1.43 (0.71
      3.29) mg/l, P=0.074) increased without an increase in pro-inflammatory cytokines.
      CONCLUSIONS: GH/IGF1 action appears to modulate the initial stage of the
      inflammatory response as well as downstream processes elucidated by levels of
      APPs. The data suggest a complicated relationship not allowing any simple
      conclusions as to whether GH/IGF1 actions have mainly pro- or anti-inflammatory
      effects in vivo.

PMID- 22408124
TI  - Pioglitazone increases bone marrow fat in type 2 diabetes: results from a
      randomized controlled trial.
AB  - OBJECTIVE: To determine the effect of pioglitazone on bone marrow fat in humans.
      DESIGN: Twenty participants in a double-blind, randomized, placebo-controlled
      trial of the skeletal effects of pioglitazone 30 mg daily in type 2 diabetes
      mellitus (T2DM) entered a 6-month substudy evaluating bone marrow fat. Main
      outcome measures were bone marrow fat in lumbar spine (L4) and proximal femur
      (intertrochanteric region), measured using magnetic resonance (MR) imaging, and
      bone mineral density (BMD), measured using dual-energy X-ray absorptiometry.
      RESULTS: after 6 months, change in the fourth lumbar vertebra (l4) bone marrow
      lipid fraction, assessed using two different methods, was greater in the
      pioglitazone group than in the placebo group (dixon method: mean (95% CI) change
      from baseline pioglitazone 1.3% (-0.3, 2.9), placebo -0.2% (-0.8, 0.4), P=0.06;
      MR spectroscopy: pioglitazone 2.5% (0.4, 4.7), placebo -1.1% (-3.7, 1.4),
      P=0.02). Similarly, the change in lipid fraction in the intertrochanteric region
      was greater in the pioglitazone group (Dixon method: mean (95% CI) change from
      baseline pioglitazone 1.3% (0.6, 1.9), placebo -0.8% (-1.8, 0.2), P=0.001).
      Within the pioglitazone group, there was no evidence of a significant
      relationship between change in marrow lipid fraction and BMD. CONCLUSIONS: Short
      term treatment with pioglitazone increases bone marrow fat in patients with T2DM.

PMID- 22408125
TI  - Refined age estimates and Paleoanthropological investigation of the Manyara Beds,
      Tanzania.
AB  - The Manyara Beds in the area of Makuyuni Village in the Lake Manyara Basin,
      Tanzania have been studied for nearly a century, but interpretations of their age
      have ranged from Middle Pleistocene to Late Pliocene. New geological,
      paleontological and archeological fieldwork was conducted at the site and has
      provided siginificant new evidence, including refined stratigraphy, radiometric
      age estimates, preliminary paleomagnetic analysis, significant new faunal
      collections, as well as stratigraphic context for some of the lithic artifacts in
      stratigraphic context. These efforts have succesfully constrained the geological
      age estimates for the Manyara Beds to between less than 0.63 to 1.3 Ma, and the
      age of the two hominin bearing localities to between 0.63 and 0.78 Ma. This new
      chronology may impact the taxonomic interpretation of the hominin remains
      recovered from the site. They also suggest that two mammalian taxa,
      Metridiochoerus compactus and Eurygnathohippus, may have some of their youngest
      known occurences in the Manyara Beds. Acheulean lithics were also found in
      stratigraphic context during this more narrow time interval. Furthermore, the
      presence of potential cut-marks on the surface of a bovid mandible may represent
      the first evidence for human modification of bones from the Manyara Beds.

PMID- 22408126
TI  - Right-handedness, lateralization and language in Neanderthals: a comment on
      Frayer et al. (2010).

PMID- 22408129
TI  - Cardiac computed tomography in the evaluation of an intra-pericardial mediastinal
      mass.

PMID- 22408128
TI  - Proteomic signatures of the desmoplastic invasion front reveal collagen type XII
      as a marker of myofibroblastic differentiation during colorectal cancer
      metastasis.
AB  - Cancer-associated fibroblasts (CAFs), represent a pivotal compartment of solid
      cancers (desmoplasia), and are causatively implicated in cancer development and
      progression. CAFs are recruited by growth factors secreted by cancer cells and
      they present a myofibroblastic phenotype, similar to the one obtained by resident
      fibroblasts during wound healing. Paracrine signaling between cancer cells and
      CAFs results in a unique protein expression profile in areas of desmoplastic
      reaction, which is speculated to drive metastasis. In an attempt to decipher
      large-scale proteomic profiles of the cancer invasive margins, we developed an in
      vitro coculture model system, based on tumor-host cell interactions between colon
      cancer cells and CAFs. Proteomic analysis of conditioned media derived from these
      cocultures coupled to mass spectrometry and bioinformatic analysis was performed
      to uncover myofibroblastic signatures of the cancer invasion front. Our analysis
      resulted in the identification and generation of a desmoplastic protein dataset
      (DPD), consisting of 152 candidate proteins of desmoplasia. By using monoculture
      exclusion datasets, a secretome algorithm and gene-expression meta-analysis in
      DPD, we specified a 22-protein "myofibroblastic signature" with putative
      importance in the regulation of colorectal cancer metastasis. Of these proteins,
      we investigated collagen type XII by immunohistochemistry, a fibril-associated
      collagen with interrupted triple helices (FACIT), whose expression has not been
      reported in desmoplastic lesions in any type of cancer. Collagen type XII was
      highly expressed in desmoplastic stroma by and around alpha-smooth muscle actin
      (alpha-SMA) positive CAFs, as well as in cancer cells lining the invasion front,
      in a small cohort of colon cancer patients. Other stromal markers, such as
      collagen type III, were also expressed in stromal collagen, but not in cancer
      cells. In a complementary fashion, gene expression meta-analysis revealed that
      COL12A1 is also an upregulated gene in colorectal cancer. Our proteomic analysis
      identified previously documented markers of tumor invasion fronts and our DPD
      could serve as a pool for future investigation of the tumor microenvironment.
      Collagen type XII is a novel candidate marker of myofibroblasts, and/or cancer
      cells undergoing dedifferentiation.

PMID- 22408130
TI  - Association between self-reported dental health status and onset of dementia: a 4
      year prospective cohort study of older Japanese adults from the Aichi
      Gerontological Evaluation Study (AGES) Project.
AB  - OBJECTIVES: Studies have shown that people with cognitive impairment have poor
      dental health. However, the direction of causality remains unknown. This
      prospective cohort study aimed to determine the association between four self
      reported dental health variables and dementia onset in older Japanese people.
      METHODS: Analysis was conducted on 4425 residents 65 years or older. Four self
      reported dental health variables included the number of teeth and/or use of
      dentures, ability to chew, presence/absence of a regular dentist, and taking care
      of dental health. Data were collected using self-administered questionnaires
      given in 2003. Records of dementia onset during 2003 to 2007 were obtained from
      municipalities in charge of the public long-term care insurance system. Age,
      income, body mass index, present illness, alcohol consumption, exercise, and
      forgetfulness were used as covariates. RESULTS: Dementia onset was recorded in
      220 participants. Univariate Cox proportional hazards models showed significant
      associations between the dental health variables and dementia onset. In models
      fully adjusted for all covariates, hazard ratios (95% confidence intervals) of
      dementia onset of respondents were as follows: 1.85 (1.04-3.31) for those with
      few teeth and without dentures; 1.25 (0.81-1.93) for those who could not chew
      very well; 1.44 (1.04-2.01) for those who did not have a regular dentist; and
      1.76 (0.96-3.20) for those who did not take care of their dental health.
      CONCLUSIONS: Few teeth without dentures and absence of a regular dentist, not
      poor mastication and poor attitudes toward dental health, were associated with
      higher risk of dementia onset in the older Japanese cohort even after adjustment
      for available covariates.

PMID- 22408131
TI  - The effect of trait rumination on adaptation to repeated stress.
AB  - OBJECTIVE: Exaggerated and prolonged cardiovascular responses to mental stress
      have been implicated in the etiology of hypertension. Rumination may play a role
      in the maintenance or reactivation of cardiovascular responses to mental stress
      and prevent cardiovascular adaptation or create sensitization on reexposure. The
      purpose of this study was to evaluate the influence of trait rumination on
      patterns of cardiovascular response adaptation after repeated exposure to a
      mental stressor. METHODS: Cardiovascular data were collected from 82
      undergraduate women during a baseline period and during a 5-minute emotional
      recall task on two separate occasions. Trait rumination was assessed using the
      Stress-Reactive Rumination Scale. RESULTS: A series of session (Sessions 1 and 2)
      by-trait rumination general linear model repeated-measures analyses of covariance
      revealed several session-by-trait rumination interactions, such that participants
      who displayed higher levels of trait rumination showed less SBP (partial eta(2) =
      0.83, p = .01), diastolic blood pressure (partial eta(2) = 0.84, p = .01), and
      heart rate (partial eta(2) = 0.82, p = .02) adaptation to the laboratory mental
      stress task at the second exposure relative to those with lower levels of trait
      rumination. CONCLUSIONS: These findings suggest that trait rumination may
      contribute to sustained increases in blood pressure by influencing adaptation to
      mental stress.

PMID- 22408132
TI  - Chronic mild stress-induced depression-like symptoms in rats and abnormalities in
      catecholamine uptake in small arteries.
AB  - OBJECTIVE: Major depression and cardiovascular diseases have a strong
      comorbidity; however, the reason for this is unknown. In the chronic mild stress
      (CMS) model of depression, only a fraction of rats develop a major feature of
      depression-anhedonia-like behavior, whereas other rats are stress resilient.
      Previous studies suggested that CMS rats also have increased total peripheral
      vascular resistance. METHODS: On the basis of CMS-induced changes of sucrose
      intake, a reliable measure for anhedonia, rats were divided into "resilient" and
      "anhedonic" groups. An interaction between hedonic status and vascular function
      was studied after 4 and 8 weeks of CMS exposure in vitro in wire myograph on
      saphenous arteries and mesenteric small arteries (MSAs) from these rats. RESULTS:
      When comparing the different experimental rat groups, arterial sensitivities to
      noradrenaline (NA) were similar under control conditions, but in the presence of
      the neuronal reuptake inhibitor cocaine, arteries from anhedonic rats were more
      sensitive to NA. No change in perivascular innervation was found, but elevated
      expression of neuronal NA transporter was detected. Inhibition of extraneuronal
      uptake with corticosterone (1 MUM) suggests that this transport is diminished in
      MSAs after CMS. The corticosterone-sensitive transporter organic cation
      cotransporter 2 was shown to be reduced in MSAs after CMS. No CMS-induced changes
      in the corticosterone-sensitive transport were found in saphenous arteries.
      CONCLUSIONS: Our results indicate that CMS-induced depression-like symptoms in
      rats are associated with changes in catecholamine uptake pathways in the vascular
      wall, which potentially modulates the effect of sympathetic innervation of
      resistance arteries.

PMID- 22408133
TI  - An integrative assessment of the psychophysiologic alterations in young women
      with recurrent major depressive disorder.
AB  - OBJECTIVE: Alterations in neuroelectrical activities coincide with major
      depressive disorder (MDD). This study examines the pattern of cerebral activity
      and cardiac autonomic parameters of euthymic women with recurrent MDD. METHODS:
      Resting electroencephalograms and electrocardiograms were recorded from 20 women
      with MDD receiving escitalopram and 40 matched and healthy women. We computed
      frontal alpha asymmetry to evaluate the interhemispheric balance. Parameters of
      heart rate variability were extracted to assess cardiac autonomic control. Sample
      entropy was used to assess the complexity of neurocardiac dynamics. The
      relationship between cardiovagal activity and alpha electroencephalogram was
      examined with a coherence analysis. RESULTS: Multivariable analysis of variance
      revealed a differential pattern of psychophysiologic variables between MDD
      patients and controls (p = .03). MDD was associated with a tendency toward lower
      left frontal activity (-0.06 [standard deviation = 0.14] versus 0.04 [0.17]
      lnMUV(2), p = .04). Discriminant analysis demonstrated more right frontal
      activation, a lower high-frequency heart rate power spectrum, and a higher ratio
      of the low- to high-frequency heart rate power spectrum in patients with MDD
      compared with controls. Residual depressive symptoms (r = -0.09 to 0.11, p = .63
      .99) and escitalopram dosage (r = -0.09 to 0.28, p = .22-.84) were not correlated
      with autonomic measures. Coherence between normalized high-frequency component of
      the heart rate power spectrum and alpha power was not significant (F3, p = .27;
      F4, p = .16). CONCLUSIONS: Euthymic women with recurrent MDD have a distinctive
      psychophysiologic profile. This profile may reflect altered frontal activation
      and a reduced cardiovagal tone in depression.

PMID- 22408134
TI  - Childhood trauma in multiple sclerosis: a case-control study.
AB  - OBJECTIVE: To investigate the association between childhood trauma and multiple
      sclerosis (MS) by comparing histories of child abuse and neglect between patients
      with MS and adults from the general population in a cross-sectional case-control
      study. Previous research has demonstrated a connection between MS and a variety
      of emotional stressors, but childhood trauma, which is known to have long-lasting
      negative consequences for physical health decades into adulthood, has not been
      studied. METHODS: The self-reported Childhood Trauma Questionnaire for the
      assessment of emotional, physical, and sexual abuse and emotional and physical
      neglect was administered to 234 patients with definite MS and 885 adults from the
      general population. RESULTS: After adjusting for sociodemographic factors and
      current depression, patients with MS scored significantly higher in all Childhood
      Trauma Questionnaire subscales apart from physical abuse and neglect than adults
      from the general population. Adjusted odds ratios for these types of childhood
      trauma were higher in the MS group than in controls, ranging from 2.0 for
      emotional neglect (95% confidence interval = 1.3-3.2) to 3.4 for emotional abuse
      (95% confidence interval = 2.0-5.7). Although childhood trauma was not associated
      with the degree of current MS-related disability, patients with MS with histories
      of physical and/or sexual abuse had significantly higher relapse rates than
      patients without early-life stress. CONCLUSIONS: Our findings suggest an
      association between childhood trauma and MS in this cross-sectional study. Larger
      prospective longitudinal studies are needed to clarify the relationship between
      early-life stress and the risk for MS in genetically susceptible individuals.

PMID- 22408135
TI  - Adolescent outcome of child ADHD in primary care setting: stability of diagnosis.
AB  - OBJECTIVE: The aim of the study was to assess the functioning of patients with
      ADHD 6 to 7 years after the diagnosis. One objective was to determine the
      stability of diagnosis, symptoms decline, subtype change, remission, and change
      of diagnosis. METHOD: In all, 101 participants were chosen for testing. All were
      interviewed for the presence of ADHD and social, academic, and peer functioning,
      and completed Youth Self-Report. The caregivers completed a Wender Utah Rating
      Scale and Child Behavior Checklist, and were asked to assess the social,
      academic, and peer functioning of their offspring. RESULTS: A total of 56% (n =
      57) still met the criteria for ADHD and 24.7% (n = 25) still met the criteria for
      hyperkinetic disorder (HKD). Subtype migration was observed. In all, 7.7% (n =
      14) were rediagnosed with Asperger's syndrome, 2.2% (n = 4) received a diagnosis
      of bipolar disorder, 2.2% (n = 4) were diagnosed with mental retardation, 1 with
      schizophrenia, and 1 with genetic disorder. CONCLUSION: The reliability of
      diagnosis was high. The rates of all subtypes of ADHD decreased. More measures
      need to be taken in terms of differential diagnosis of ADHD and Asperger's
      Syndrome.

PMID- 22408136
TI  - Advancing the discussion about systematic classroom behavioral observation, a
      product review of Tenny, J. (2010). eCOVE observation software. Pacific City, OR:
      eCOVE Software, LLC.
AB  - Applied child psychologists and behavioral consultants often use systematic
      behavioral observations to inform the psychological assessment and intervention
      development process for children referred for attention and hyperactivity
      problems. This article provides a review of the 2010 version of the eCOVE
      classroom observation software in terms of its utility in tracking the progress
      of children with attention and hyperactive behaviors and its use in evaluating
      teacher behaviors that may impede or promote children's attention and positive
      behavior. The eCOVE shows promise as an efficient tool for psychologists and
      behavioral consultants who want to evaluate the effects of interventions for
      children with symptoms of ADHD, ODD, mood disorders and learning disorders;
      however, some research-based improvements for future models are suggested. The
      reviewers also share their firsthand experience in using eCOVE to evaluate
      teacher and student behavior exhibited on a television show about teaching urban
      high school students and during a movie about an eccentric new kindergarten
      teacher. Rich examples are provided of using strategic behavioral observations to
      reveal how to improve the classroom environment so as to facilitate attention,
      motivation and positive behavior among youth. Broader implications for enhancing
      the use of systematic behavioral observations in the assessment of children and
      adolescents with attention disorders and related behavioral problems are
      discussed. Key issues are examined such as the use of behavioral observations
      during psychological consultation to prevent the previously found gender bias in
      referrals for ADHD. Using behavioral observations to enhance differential
      diagnosis is also discussed. 

PMID- 22408137
TI  - Essential role for telomerase in chronic myeloid leukemia induced by BCR-ABL in
      mice.
AB  - The telomerase protein is constitutively activated in malignant cells from many
      patients with cancer, including the chronic myeloid leukemia (CML), but whether
      telomerase is essential for the pathogenesis of this disease is not known. Here,
      we used telomerase deficient mice to determine the requirement for telomerase in
      CML induced by BCR-ABL in mouse models of CML. Loss of one telomerase allele or
      complete deletion of telomerase prevented the development of leukemia induced by
      BCR-ABL. However, BCR-ABL was expressed and active in telomerase heterozygous and
      null leukemic hematopoietic stem cells. These results demonstrate that telomerase
      is essential for oncogene-induced reprogramming of hematopoietic stem cells in
      CML development and validate telomerase and the genes it regulates as targets for
      therapy in CML.

PMID- 22408138
TI  - Validation of the National Eye Institute Visual Function Questionnaire-25 (NEI
      VFQ-25) in age-related macular degeneration.

PMID- 22408139
TI  - The effect of the anterior ocular structures on the fluid dynamics in eyes with
      gas tamponades.

PMID- 22408140
TI  - Epidemiology and prognostic determinants of bacteraemic biliary tract infection.
AB  - OBJECTIVES: To determine the epidemiology of bacteraemia due to biliary tract
      infection (BTI) and to identify independent predictors of mortality. METHODS:
      This study was part of a bloodstream infection surveillance study that
      prospectively collected data on consecutive patients with bacteraemia in our
      institution from 1991 to 2010. BTI was the confirmed source of 1373 patients with
      bacteraemia, and the independent prognostic factors of 30 day mortality were
      determined. RESULTS: The mean age of patients with biliary sepsis was 71 years
      (+/- 14 years). The most frequent comorbidities were biliary lithiasis and solid
      organ cancer [484 cases (35%) and 362 cases (26%), respectively]. The BTI was
      healthcare-associated in 33% of patients. Shock and mortality accounted for 209
      and 126 cases, respectively (15% and 9%). The most frequent microorganisms
      isolated were Escherichia coli (749, 55%), Klebsiella spp. (240, 17%),
      Enterococcus spp. (171, 12%), Pseudomonas aeruginosa (86, 6%) and Enterobacter
      spp. (63, 5%). There were 47 (3%) cefotaxime-resistant (CTX-R) E. coli or
      Klebsiella spp. Inappropriate empirical antibiotic treatment was an independent
      factor associated with mortality (OR 1.4, 95% CI 1.1-1.7). Inappropriate
      empirical treatment was more frequent in P. aeruginosa and CTX-R
      Enterobacteriaceae bacteraemia. These microorganisms were significantly more
      common in patients with previous antibiotic therapy, solid-organ cancer or
      transplantation and in healthcare-associated bacteraemia. CONCLUSIONS: In
      patients with bacteraemic BTI, inappropriate empirical therapy was more frequent
      in P. aeruginosa and CTX-R Enterobacteriaceae infection and was associated with a
      higher mortality rate. In patients with bacteraemia due to BTI and solid-organ
      cancer or transplantation, healthcare-associated infection or previous antibiotic
      treatment, initial therapy with piperacillin/tazobactam or a carbapenem would be
      advisable.

PMID- 22408141
TI  - Cardiac dysfunction exacerbated by endocrinopathies in Friedreich ataxia: a case
      series.
AB  - Friedreich ataxia is a neurodegenerative disease characterized by gait
      abnormalities, cardiomyopathy, and diabetes. Congestive heart failure was
      recently reported as the most frequent cause of Friedreich ataxia mortality.
      Cardiac dysfunction is suspected to result from a frataxin deficiency that leads
      to oxidative damage in cardiac tissues and possible metabolic syndrome
      characteristics. In this report, we describe 2 patient cases whose cardiac
      function worsened dramatically in the presence of underlying endocrinopathies. We
      report on one Friedreich ataxia teenager with previously undiagnosed diabetes
      that resulted in diabetic ketoacidosis and rapid progression to severe left
      ventricular dysfunction. We also describe a Friedreich ataxia teenager whose
      underlying Graves disease led to rapid worsening of known cardiomyopathy. Cardiac
      management and treatment for the endocrinopathies returned cardiac function to
      baseline. We conclude that screening for and awareness of underlying
      endocrinopathies in Friedreich ataxia may provide novel therapeutic targets for
      preventing Friedreich ataxia-associated cardiac dysfunction.

PMID- 22408142
TI  - Variations in hospitalization outcomes in children admitted with seizures between
      2003 and 2006.
AB  - Economic factors play an increasingly important role in the management of medical
      conditions. This study evaluated the economic impact of seizures in children in
      the United States using a large national data set known as the Kids' Inpatient
      Database (KID). The aim of this study was to characterize hospitalizations
      including total costs, length of stay, and variations in care. There were 63,719
      pediatric seizure discharges in the 2003 and 2006 Kids' Inpatient Database. The
      mean hospital cost was $4105 in 2003 and $4553 in 2006. Patients with government
      insurance as the primary payer had a significantly longer length of stay compared
      with private insurance or self-pay patients (P < .0001); however, there was no
      significant difference in the total costs of hospitalization between the
      different payer groups. This analysis highlights multiple disparities of health
      care utilization in pediatric seizure management. In a stressful economic
      climate, all health care entities must focus on cost management of pediatric
      seizure.

PMID- 22408143
TI  - Survey of subacute sclerosing panencephalitis in Japan.
AB  - Investigators conducted a retrospective epidemiological study of subacute
      sclerosing panencephalitis, a fatal disease caused by measles infection, over the
      past few years in Japan. Data on 118 cases obtained from a questionnaire sent to
      attending physicians were analyzed. The annual incidence of subacute sclerosing
      panencephalitis was approximately 0.03 cases per million from 2001 to 2005.
      Children infected with measles at a young age (<12 months) showed a high
      incidence of subacute sclerosing panencephalitis, and those infected before 6
      months of age showed earlier onset. Because a positive correlation was found
      between the prevalence of measles and the onset of subacute sclerosing
      panencephalitis, particularly among children infected at an early age, it is
      vital to eradicate measles infection by vaccination.

PMID- 22408144
TI  - Lissencephaly and band heterotopia: LIS1, TUBA1A, and DCX mutations in Hungary.
AB  - The spectrum of lissencephaly ranges from absent (agyria) or decreased
      (pachygyria) convolutions to less severe malformation known as subcortical band
      heterotopia. Mutations involving LIS1 and TUBA1A result in the classic form of
      lissencephaly, whereas mutations of the DCX gene cause lissencephaly in males and
      subcortical band heterotopia in females. This report describes the clinical
      manifestations and imaging and genetic findings in 2 boys with lissencephaly and
      a girl with subcortical band heterotopia. An ovel mutation (c.83_84delAT,
      p.Tyr28Phefs*31) was identified in LIS1 in 1 of the boys with lissencephaly and
      another novel mutation (c.200delG, p.Ile68Leufs*87) was found in DCX in the girl
      with subcortical band heterotopia. The mutations appeared in the first half of
      the genes and are predicted to result in truncated proteins. A mutation was found
      in the TUBA1A gene (c.1205G>A, p.Arg402His) in the other boy. This mutation
      affects the folding of tubulin heterodimers, changing the interactions with
      proteins that bind microtubules.

PMID- 22408145
TI  - Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis mimicking a primary
      psychiatric disorder in an adolescent.
AB  - Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis likely has a wider
      clinical spectrum than previously recognized. This article reports a previously
      healthy 16-year-old girl who was diagnosed with anti-NMDA receptor encephalitis 3
      months after onset of severe depression with psychotic features. She had no
      neurological manifestations, and cerebral magnetic resonance imaging (MRI) was
      normal. Slow background on electroencephalogram and an oligoclonal band in the
      cerebrospinal fluid prompted the search for anti-NMDA receptor antibodies. She
      markedly improved over time but remained with mild neuropsychological sequelae
      after a trial of late immunotherapy. Only a high index of suspicion enables
      recognition of the milder forms of the disease masquerading as primary
      psychiatric disorders.

PMID- 22408146
TI  - Myasthenia mimicking monocular elevation deficiency.
AB  - Monocular elevation deficiency is the inability to elevate the eye in abduction
      and adduction. Myasthenia gravis could mimic any pattern of ophthalmoplegia.
      However, myasthenia gravis mimicking monocular elevation deficiency appears to be
      very rare. A 12-month-old girl presented with the inability to elevate the left
      eye and blepharoptosis from 3 months of age. A neostigmine test showed a weakly
      positive response. Repetitive stimulation of the left orbicularis oculi produced
      no decremental response. Three assays for acetylcholine receptor antibodies were
      negative. Placing ice over the lids definitely improved left blepharoptosis. In
      conclusion, myasthenia gravis could mimic elevation deficiency. An ice test could
      be very helpful in making the diagnosis. Myasthenia gravis should be included in
      the differential diagnosis of monocular elevation deficiency even at a young age.

PMID- 22408147
TI  - Clinical features, survival times and COX-1 and COX-2 expression in cats with
      transitional cell carcinoma of the urinary bladder treated with meloxicam.
AB  - Records of 11 cats with transitional cell carcinoma of the urinary bladder, which
      had been treated with meloxicam, were reviewed for signalment, duration of
      clinical signs prior to diagnosis, results of diagnostic imaging, whether or not
      concurrent surgery was performed and survival. Immunohistochemical expression of
      cyclo-oxygenase-1 (COX-1) and cyclo-oxygenase-2 (COX-2) was assessed in the
      tumours of seven cats. Tumour location varied greatly. The cats had a mean age of
      13 years. Three cats had a previous diagnosis of feline idiopathic cystitis of up
      to 2008 days duration. Ten of the cats showed clinical improvement (reduction of
      haematuria and/or dysuria), with a mean survival time (MST) of 311 days (range 10
      1064); 1-year survival of 50%. All seven bladders assessed for COX staining were
      COX-1 positive and five were COX-2 positive. The MST for the COX-2-positive cats
      was 123 days, the MST for the COX-2-negative cases was 375 days.

PMID- 22408148
TI  - A case of feline primary inflammatory mammary carcinoma: clinicopathological and
      immunohistochemical findings.
AB  - The clinicopathological and immunohistochemical findings of a primary feline
      mammary tumour with features similar to human and canine primary inflammatory
      carcinoma are described for the first time. The cat presented to the clinic for
      the rapid onset of oedema, severe erythema, local pain and warmth of the inguinal
      region, with a pustular-to-nodular cutaneous lesion in association with an ill
      defined underlying mass. An epithelial malignant tumour was diagnosed by
      cytological investigation. Necropsy revealed a thickening of the skin with oedema
      of the subcutis in the right inguinal area, and regional and distant metastases.
      Histology showed an unencapsulated tubulopapillary proliferation of malignant
      epithelial cells, with a massive embolisation in the dermal lymphatics and a mild
      inflammatory infiltrate. Through immunohistochemistry, the tumour was found to be
      oestrogen (ER)-alpha-, androgen (AR)- and progesterone (PR)-negative; neoplastic
      cells were ER-alpha, AR-negative and focally PR-positive. An irregular, mild and
      focal HER-2 immunoreactivity was present (score +1, non-HER-2 overexpressing).
      The neoplastic cells were cyclo-oxygenase-2 and vascular endothelial growth
      factor positive.

PMID- 22408149
TI  - A retrospective analysis of cervical spine radiography in a specialist trauma
      unit for head injury.
AB  - OBJECTIVES: The performance of an adequate and complete series of cervical
      radiographs in the trauma patient is essential in order to ensure safe trauma
      management. Eastern Association for the Surgery of Trauma (EAST) has produced
      widely recognised guidelines with which trauma units should comply. The aim of
      the study is to ascertain the adequacy of cervical spine imaging of trauma
      patients in a specialist trauma unit (head injury) using EAST guidelines as gold
      standard. An additional assessment of institutional reporting accuracy is
      conducted. METHODS: Data were examined from 81 consecutive trauma patients
      requiring cervical spine radiography. EAST guidelines were applied
      retrospectively to this cohort in order to define guideline compliance. An
      additional cohort assessment was conducted addressing the accuracy and adequacy
      of the formal institutional reports associated with these radiographs. RESULTS:
      99% of patients undergoing a full cervical trauma series had at least one
      inadequate initial image. Of these, 85% had at least one inadequate lateral or
      peg view (of which 26% did not have repeat radiographs performed). Over one-third
      of all trauma patients left the emergency department with inadequate cervical
      spine imaging (incomplete cervical spine series or inadequate films). From the
      institutional reporting perspective, only 27% of all inadequate initial and
      repeat lateral or peg views were subsequently explicitly reported as being
      inadequate. DISCUSSION: These findings call into question current practice.
      Clearly, multiple confounders exist in the context of process variability in a
      heterogeneous population such as that attending an emergency department. This
      study offer solutions to address this problem.

PMID- 22408150
TI  - Contact tracing in pulmonary and non-pulmonary tuberculosis.
AB  - AIM: The aim of our study was to determine the effectiveness of contact tracing
      for both pulmonary and non-pulmonary tuberculosis (TB). METHODS: The authors
      studied contact tracing in South East of Scotland, Edinburgh TB Clinic, UK, for 3
      years. New index cases of both pulmonary and non-pulmonary TB were identified
      from reviewing TB nurses records. Pulmonary involvement was excluded from all non
      pulmonary cases. Active TB was diagnosed as per the national TB guidelines.
      Latent TB was diagnosed based on history, tuberculin skin test and interferon
      gamma release assay. TB contacts were identified from reviewing TB nurses notes
      on index TB patients. A positive screening episode was defined as identification
      of either active or latent TB in a contact following relevant investigations.
      RESULTS: Total number of positive screening episodes for pulmonary TB was 43.1%
      and non-pulmonary TB was 26.1%. Of these, 78.8% were household contacts and 21.2%
      were casual contacts. CONCLUSION: Contact tracing in low-prevalence TB countries,
      for both pulmonary and non-pulmonary TB, is an essential intervention to identify
      and reduce the number of infected patients that will progress to active disease.
      This is the key for effective TB control.

PMID- 22408151
TI  - Development and evaluation of a nurse-led transient elastography service for the
      staging of hepatic fibrosis in patients with suspected chronic liver disease.
AB  - BACKGROUND AND AIMS: Establishing the presence of fibrosis and cirrhosis is an
      essential step in the management of patients with chronic liver diseases (CLD).
      Liver stiffness measurement (LSM) based on transient elastography (TE) correlates
      well with the stages of liver fibrosis and has been developed as a non-invasive
      alternative to liver biopsy. The studies performed to date have used physician
      operators. With the potential use of TE for screening of community-based
      populations for liver disease, we aimed to evaluate the performance of nurse
      operators. DESIGN: Retrospective analysis. METHODS: We reviewed the reliability
      and accuracy of LSMs performed by the nurse-led TE service at Queen's Medical
      Centre, Nottingham between May 2009 and January 2011. Consecutive patients with
      suspected CLD who underwent LSM were included. RESULTS: Over the study period 585
      LSMs were performed. Analysis was performed on the 208 patients where LSM could
      be compared with liver biopsy findings. Of these 11 (5.3%) had unreliable LSM
      results (less than 10 valid shots or success rate <60%). There were no LSM
      failures. Inadequate liver biopsy specimen led to exclusion in 26 (12.5%)
      patients. For the detection of significant fibrosis (Ishak stage >2), a
      sensitivity of 0.78 and specificity of 0.81 was obtained, with a cut-off value of
      8 kPa. Using a cut-off value of 13 kPa for detection of cirrhosis, a sensitivity
      and specificity of 0.8 and 0.92 was obtained. CONCLUSION: We have demonstrated
      that a nurse-led TE service can produce a low level of unreliable results and LSM
      failures, with comparable sensitivity and specificity for detecting significant
      fibrosis and cirrhosis to those reported in the literature. The demands on the
      use of TE could potentially be eased through the introduction of nurse-led
      service delivery.

PMID- 22408152
TI  - A 20-year retained guidewire, should it be removed?

PMID- 22408153
TI  - Inequalities in outcomes of acute kidney injury in England.
AB  - BACKGROUND: Renal replacement is managed by renal specialists and is well
      documented in national registries. In contrast, nation-wide data on acute kidney
      injury (AKI) are difficult to capture as it presents in many different ways to
      all acute hospitals. This paucity impacts on the coordination of appropriate
      services. AIMS: We have set out to use all the information submitted by all
      hospitals in England to identify emergency patients in whom AKI was a major
      contributor to their hospital stay. We then examined workload in relation to
      specialist provision and outcomes of care. DESIGN AND METHODS: All English
      hospitals submit a sequential list of International Statistical Classification of
      Diseases and Related Health Problems, 10th Revision (ICD 10) codes to describe
      the diagnosis of each admission. An algorithm was applied to all emergency
      admissions over a 2-year period to identify AKI. The level of renal specialist
      care available within each hospital trust was compared with patient outcomes,
      including 30-day mortality. RESULTS: The incidence of AKI was 1.34% of all
      emergency admissions. The numbers and types of AKI cases were similar in all
      trusts, regardless of the service available. Thirty-day mortality was 30.0%. More
      than half the acute hospitals did not have on-site renal specialists and their
      AKI mortality rates were significantly higher (P < 0.001). These differences
      persisted despite adjusting for multiple variables. CONCLUSION: The country has
      created specialist renal units in 45% of hospital trusts, but AKI presents as
      emergencies to all hospitals and there is an increased risk of mortality in the
      55% of trusts without renal specialists.

PMID- 22408154
TI  - Beau's lines.

PMID- 22408155
TI  - Identification of genes involved in the acetamidino group modification of the
      flagellin N-linked glycan of Methanococcus maripaludis.
AB  - N-linked glycosylation of protein is a posttranslational modification found in
      all three domains of life. The flagellin proteins of the archaeon Methanococcus
      maripaludis are known to be modified with an N-linked tetrasaccharide consisting
      of N-acetylgalactosamine (GalNAc), a diacetylated glucuronic acid (GlcNAc3NAc),
      an acetylated and acetamidino-modified mannuronic acid with a substituted
      threonine group (ManNAc3NAmA6Thr), and a novel terminal sugar residue [(5S)-2
      acetamido-2,4-dideoxy-5-O-methyl-alpha-L-erythro-hexos-5-ulo-1,5-pyranose]. To
      identify genes involved in biosynthesis of the component sugars of this glycan,
      three genes, mmp1081, mmp1082, and mmp1083, were targeted for in-frame deletion,
      based on their annotation and proximity to glycosyltransferase genes known to be
      involved in assembly of the glycan. Mutants carrying a deletion in any of these
      three genes remained flagellated and motile. A strain with a deletion of mmp1081
      had lower-molecular-mass flagellins in Western blots. Mass spectrometry of
      purified flagella revealed a truncated glycan with the terminal sugar absent and
      the threonine residue and the acetamidino group missing from the third sugar. No
      glycan modification was seen in either the Deltammp1082 or Deltammp1083 mutant
      grown in complex Balch III medium. However, a glycan identical to the
      Deltammp1081 glycan was observed when the Deltammp1082 or Deltammp1083 mutant was
      grown under ammonia-limited conditions. We hypothesize that MMP1082 generates
      ammonia and tunnels it through MMP1083 to MMP1081, which acts as the
      amidotransferase, modifying the third sugar residue of the M. maripaludis glycan
      with the acetamidino group.

PMID- 22408156
TI  - The LovK-LovR two-component system is a regulator of the general stress pathway
      in Caulobacter crescentus.
AB  - A conserved set of regulators control the general stress response in Caulobacter
      crescentus, including sigma(T), its anti-sigma factor NepR, the anti-anti-sigma
      factor PhyR, and the transmembrane sensor kinase PhyK. We report that the soluble
      histidine kinase LovK and the single-domain response regulator LovR also function
      within the C. crescentus general stress pathway. Our genetic data support a model
      in which LovK-LovR functions upstream of sigma(T) by controlling the
      phosphorylation state and thus anti-anti-sigma activity of PhyR. Transcription of
      lovK and lovR is independently activated by stress through a mechanism that
      requires sigT and phyR. Conversely, lovK and lovR function together to repress
      transcription of the general stress regulon. Concordant with a functional role of
      the LovK-LovR two-component system as a negative regulator of the general stress
      pathway, lovK-lovR-null mutants exhibit increased cell survival after osmotic
      stress, while coordinate overexpression of lovK and lovR attenuates cell survival
      relative to that of the wild type. Notably, lovK can complement the
      transcriptional and cell survival defects of a phyK-null mutant when lovR is
      deleted. Moreover, in this same genetic background, sigma(T)-dependent
      transcription is activated in response to osmotic stress. This result suggests
      that flavin-binding LOV (light, oxygen, or voltage) histidine kinases are
      competent to perceive cytoplasmic signals in addition to the environmental signal
      blue light. We conclude that the PhyK-PhyR and LovK-LovR two-component signaling
      systems coordinately regulate stress physiology in C. crescentus.

PMID- 22408157
TI  - Characterization of the CRISPR/Cas subtype I-A system of the hyperthermophilic
      crenarchaeon Thermoproteus tenax.
AB  - CRISPR (clustered regularly interspaced short palindromic repeats) elements and
      cas (CRISPR-associated) genes are widespread in Bacteria and Archaea. The
      CRISPR/Cas system operates as a defense mechanism against mobile genetic elements
      (i.e., viruses or plasmids). Here, we investigate seven CRISPR loci in the genome
      of the crenarchaeon Thermoproteus tenax that include spacers with significant
      similarity not only to archaeal viruses but also to T. tenax genes. The analysis
      of CRISPR RNA (crRNA) transcription reveals transcripts of a length between 50
      and 130 nucleotides, demonstrating the processing of larger crRNA precursors. The
      organization of identified cas genes resembles CRISPR/Cas subtype I-A, and the
      core cas genes are shown to be arranged on two polycistronic transcripts: cascis
      (cas4, cas1/2, and csa1) and cascade (csa5, cas7, cas5a, cas3, cas3', and
      cas8a2). Changes in the environmental parameters such as UV-light exposure or
      high ionic strength modulate cas gene transcription. Two reconstitution protocols
      were established for the production of two discrete multipartite Cas protein
      complexes that correspond to their operonic gene arrangement. These data provide
      insights into the specialized mechanisms of an archaeal CRISPR/Cas system and
      allow selective functional analyses of Cas protein complexes in the future.

PMID- 22408158
TI  - Mutations derived from the thermophilic polyhydroxyalkanoate synthase PhaC
      enhance the thermostability and activity of PhaC from Cupriavidus necator H16.
AB  - The thermophile Cupriavidus sp. strain S-6 accumulated polyhydroxybutyrate (PHB)
      from glucose at 50 degrees C. A 9.0-kbp EcoRI fragment cloned from the genomic
      DNA of Cupriavidus sp. S-6 enabled Escherichia coli XL1-Blue to synthesize PHB at
      45 degrees C. Nucleotide sequence analysis showed a pha locus in the clone. The
      thermophilic polyhydroxyalkanoate (PHA) synthase (PhaC(Csp)) shared 81% identity
      with mesophilic PhaC of Cupriavidus necator H16. The diversity between these two
      strains was found dominantly on their N and C termini, while the middle regions
      were highly homologous (92% identity). We constructed four chimeras of mesophilic
      and thermophilic phaC genes to explore the mutations related to its
      thermostability. Among the chimeras, only PhaC(H16beta), which was PhaC(H16)
      bearing 30 point mutations derived from the middle region of PhaC(Csp),
      accumulated a high content of PHB (65% [dry weight]) at 45 degrees C. The chimera
      phaC(H16)(beta) and two parental PHA synthase genes were overexpressed in E. coli
      BLR(DE3) cells and purified. At 30 degrees C, the specific activity of the
      chimera PhaC(H16beta) (172 +/- 17.8 U/mg) was 3.45-fold higher than that of the
      parental enzyme PhaC(H16) (50 +/- 5.2 U/mg). At 45 degrees C, the half-life of
      the chimera PhaC(H16beta) (11.2 h) was 127-fold longer than that of PhaC(H16)
      (5.3 min). Furthermore, the chimera PhaC(H16beta) accumulated 1.55-fold (59% [dry
      weight]) more PHA content than the parental enzyme PhaC(H16) (38% [dry weight])
      at 37 degrees C. This study reveals a limited number of point mutations which
      enhance not only thermostability but also PhaC(H16) activity. The highly
      thermostable and active PHA synthase will provide advantages for its promising
      applications to in vitro PHA synthesis and recombinant E. coli PHA fermentation.

PMID- 22408159
TI  - Functional characterization of UDP-glucose:undecaprenyl-phosphate glucose-1
      phosphate transferases of Escherichia coli and Caulobacter crescentus.
AB  - Escherichia coli K-12 WcaJ and the Caulobacter crescentus HfsE, PssY, and PssZ
      enzymes are predicted to initiate the synthesis of colanic acid (CA) capsule and
      holdfast polysaccharide, respectively. These proteins belong to a prokaryotic
      family of membrane enzymes that catalyze the formation of a phosphoanhydride bond
      joining a hexose-1-phosphate with undecaprenyl phosphate (Und-P). In this study,
      in vivo complementation assays of an E. coli K-12 wcaJ mutant demonstrated that
      WcaJ and PssY can complement CA synthesis. Furthermore, WcaJ can restore holdfast
      production in C. crescentus. In vitro transferase assays demonstrated that both
      WcaJ and PssY utilize UDP-glucose but not UDP-galactose. However, in a strain of
      Salmonella enterica serovar Typhimurium deficient in the WbaP O antigen
      initiating galactosyltransferase, complementation with WcaJ or PssY resulted in O
      antigen production. Gas chromatography-mass spectrometry (GC-MS) analysis of the
      lipopolysaccharide (LPS) revealed the attachment of both CA and O-antigen
      molecules to lipid A-core oligosaccharide (OS). Therefore, while UDP-glucose is
      the preferred substrate of WcaJ and PssY, these enzymes can also utilize UDP
      galactose. This unexpected feature of WcaJ and PssY may help to map specific
      residues responsible for the nucleotide diphosphate specificity of these or
      similar enzymes. Also, the reconstitution of O-antigen synthesis in Salmonella,
      CA capsule synthesis in E. coli, and holdfast synthesis provide biological assays
      of high sensitivity to examine the sugar-1-phosphate transferase specificity of
      heterologous proteins.

PMID- 22408160
TI  - Regulation and function of pilus island 1 in group B streptococcus.
AB  - Group B streptococcus (GBS) pili may enhance colonization and infection by
      mediating bacterial adhesion to host cells, invasion across endothelial and
      epithelial barriers, and resistance to bacterial ingestion and killing by host
      phagocytes. However, it remains unclear how pilus expression is regulated and how
      modulation of pilus production affects GBS interactions with the human host. We
      investigated the regulation and function of pilus island 1 (PI-1) pili in GBS
      strain 2603. We found that PI-1 gene expression was controlled by the CsrRS two
      component system, by Ape1, an AraC-type regulator encoded by a divergently
      transcribed gene immediately upstream of PI-1, and by environmental pH. The
      response regulator CsrR repressed expression of Ape1, which is an activator of PI
      1 gene expression. In addition, CsrR repressed PI-1 gene expression directly,
      independent of its regulation of Ape1. In vitro assays demonstrated specific
      binding of both CsrR and Ape1 to chromosomal DNA sequences upstream of PI-1.
      Pilus gene expression was activated by acidic pH, and this effect was independent
      of CsrRS and Ape1. Unexpectedly, characterization of PI-1 deletion mutants
      revealed that PI-1 pili do not mediate adhesion of strain 2603 to A549
      respiratory epithelial cells, ME180 cervical cells, or VK2 vaginal cells in
      vitro. PI-1 pili reduced internalization and intracellular killing of GBS by
      human monocyte-derived macrophages, by approximately 50%, but did not influence
      complement-mediated opsonophagocytic killing by human neutrophils. These findings
      shed new light on the complex nature of pilus regulation and function in
      modulating GBS interactions with the human host.

PMID- 22408161
TI  - Identification and characterization of a succinyl-coenzyme A (CoA):benzoate CoA
      transferase in Geobacter metallireducens.
AB  - Geobacter metallireducens is a Fe(III)-respiring deltaproteobacterium and serves
      as a model organism for aromatic compound-degrading, obligately anaerobic
      bacteria. In this study, a genetic system was established for G. metallireducens
      using nitrate as an alternative electron acceptor. Surprisingly, disruption of
      the benzoate-induced bamY gene, encoding a benzoate coenzyme A (CoA) ligase,
      reproducibly showed an increased biomass yield in comparison to the wild type
      during growth with benzoate but not during growth with acetate. Complementation
      of bamY in trans converted the biomass yield back to the wild-type level. Growth
      of the bamY mutant with benzoate can be rationalized by the identification of a
      previously unknown succinyl-CoA:benzoate CoA transferase activity; it represents
      an additional, energetically less demanding mode of benzoate activation. The
      activity was highly enriched from extracts of cells grown on benzoate, yielding a
      50-kDa protein band; mass spectrometric analysis identified the corresponding
      benzoate-induced gene annotated as a CoA transferase. It was heterologously
      expressed in Escherichia coli and characterized as a specific succinyl
      CoA:benzoate CoA transferase. The newly identified enzyme in conjunction with a
      benzoate-induced succinyl-CoA synthetase links the tricarboxylic acid cycle to
      the upper benzoyl-CoA degradation pathway during growth on aromatic growth
      substrates.

PMID- 22408162
TI  - Two isoforms of Geobacter sulfurreducens PilA have distinct roles in pilus
      biogenesis, cytochrome localization, extracellular electron transfer, and biofilm
      formation.
AB  - Type IV pili of Geobacter sulfurreducens are composed of PilA monomers and are
      essential for long-range extracellular electron transfer to insoluble Fe(III)
      oxides and graphite anodes. A previous analysis of pilA expression indicated that
      transcription was initiated at two positions, with two predicted ribosome-binding
      sites and translation start codons, potentially producing two PilA preprotein
      isoforms. The present study supports the existence of two functional translation
      start codons for pilA and identifies two isoforms (short and long) of the PilA
      preprotein. The short PilA isoform is found predominantly in an intracellular
      fraction. It seems to stabilize the long isoform and to influence the secretion
      of several outer-surface c-type cytochromes. The long PilA isoform is required
      for secretion of PilA to the outer cell surface, a process that requires
      coexpression of pilA with nine downstream genes. The long isoform was determined
      to be essential for biofilm formation on certain surfaces, for optimum current
      production in microbial fuel cells, and for growth on insoluble Fe(III) oxides.

PMID- 22408163
TI  - Genetic control of osmoadaptive glycine betaine synthesis in Bacillus subtilis
      through the choline-sensing and glycine betaine-responsive GbsR repressor.
AB  - Synthesis of the compatible solute glycine betaine confers a considerable degree
      of osmotic stress tolerance to Bacillus subtilis. This osmoprotectant is produced
      through the uptake of the precursor choline via the osmotically inducible OpuB
      and OpuC ABC transporters and a subsequent two-step oxidation process by the GbsB
      and GbsA enzymes. We characterized a regulatory protein, GbsR, controlling the
      transcription of both the structural genes for the glycine betaine biosynthetic
      enzymes (gbsAB) and those for the choline-specific OpuB transporter (opuB) but
      not of that for the promiscuous OpuC transporter. GbsR acts genetically as a
      repressor and functions as an intracellular choline sensor. Spectroscopic
      analysis of the purified GbsR protein showed that it binds the inducer choline
      with an apparent K(D) (equilibrium dissociation constant) of approximately 165
      MUM. Based on the X-ray structure of a protein (Mj223) from Methanococcus
      jannaschii, a homology model for GbsR was derived. Inspection of this GbsR in
      silico model revealed a possible ligand-binding pocket for choline resembling
      those of known choline-binding sites present in solute receptors of microbial ABC
      transporters, e.g., that of the OpuBC ligand-binding protein of the OpuB ABC
      transporter. GbsR was not only needed to control gbsAB and opuB expression in
      response to choline availability but also required to genetically tune down
      glycine betaine production once cellular adjustment to high osmolarity has been
      achieved. The GbsR regulatory protein from B. subtilis thus records and
      integrates cellular and environmental signals for both the onset and the
      repression of the synthesis of the osmoprotectant glycine betaine.

PMID- 22408164
TI  - Phosphatidylethanolamine of Helicobacter pylori functions as a steroid-binding
      lipid in the assimilation of free cholesterol and 3beta-hydroxl steroids into the
      bacterial cell membrane.
AB  - One of the unique features of Helicobacter pylori is its ability to assimilate
      free-cholesterol (FC) into its membranes. Via FC assimilation, H. pylori
      strengthens the membrane lipid barrier and/or evades the host immune system. No
      previous studies, however, have investigated the FC uptake mechanisms of the H.
      pylori cell. Phosphatidylethanolamine (PE) is the most prevalent lipid component
      of bacteria, including H. pylori, but the function of PE remains unclear. We were
      therefore interested in H. pylori PE (HpPE) and investigated the interaction of
      its PE with cholesterols. The PE isolated from H. pylori underwent a unique
      molecular interaction with FC, cholesterol ester (CE), and 2,6-di-O-methyl-beta
      cyclodextrin (dMbetaCD), a sterol solubilizer. HpPE interacted not only with the
      FC molecule, but also with the FC-dMbetaCD inclusion complex. In contrast,
      Escherichia coli PE (EcPE), prepared as a reference PE, seemed to bind only FC,
      and only via a hydrophobic interaction, without binding dMbetaCD. HpPE was
      clearly more potent than EcPE in binding FC. Intriguingly, HpPE had a negligible
      affinity for CE, while EcPE had a high affinity for CE, comparable to its
      affinity for FC. Further, HpPE interacted with 3beta-OH steroids, pregnenolone
      and dehydroepiandrosterone, in the absence of dMbetaCD. Gas chromatogram-mass
      spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) analyses
      revealed that the fatty acid compositions of HpPE were quite distinct from those
      of EcPE, and the C(14:0) fatty acid in the HpPE molecule was found to be
      significant in binding FC selectively. These results indicate that PE is a key
      candidate of nonesterified steroid-binding lipids in H. pylori.

PMID- 22408165
TI  - The distal ExsA-binding site in Pseudomonas aeruginosa type III secretion system
      promoters is the primary determinant for promoter-specific properties.
AB  - Transcription of the Pseudomonas aeruginosa type III secretion system is
      controlled by ExsA, a member of the AraC/XylS family of regulators. Each ExsA
      dependent promoter contains two adjacent binding sites for monomeric ExsA. The
      promoter-proximal site (binding site 1) consists of highly conserved GnC and
      TGnnA sequences that are individually recognized by the two helix-turn-helix
      (HTH) DNA-binding motifs of an ExsA monomer. While the GnC and TGnnA sequences
      are important for binding to site 1, the promoter-distal binding sites (site 2)
      lack obvious similarity among themselves or with binding site 1. In the present
      study, we demonstrate that site 2 in the P(exsC) promoter region contains a GnC
      sequence that is functionally equivalent to the GnC in site 1 and recognized by
      the first HTH motif of an ExsA monomer. Likewise, the second HTH interacts with
      an adenine residue in binding site 2. Although several candidate GnC sequences
      are also present in site 2 of the P(exsD), P(exoT), and P(pcrG) promoters, the
      GnC sequences were not required for ExsA-dependent transcription or ExsA binding.
      A comparison of hybrid promoters composed of binding site 2 from one promoter
      fused to binding site 1 derived from another promoter indicates that ExsA-binding
      affinity, promoter strength, and the degree of promoter bending are properties
      that are largely determined by binding site 2. Based on these data, we propose
      that the manner in which ExsA interacts with binding site 2 at the P(exsC)
      promoter is distinct from the interactions occurring at other promoters.

PMID- 22408166
TI  - Lactate utilization is regulated by the FadR-type regulator LldR in Pseudomonas
      aeruginosa.
AB  - NAD-independent L-lactate dehydrogenase (l-iLDH) and NAD-independent D-lactate
      dehydrogenase (D-iLDH) activities are induced coordinately by either enantiomer
      of lactate in Pseudomonas strains. Inspection of the genomic sequences of
      different Pseudomonas strains revealed that the lldPDE operon comprises 3 genes,
      lldP (encoding a lactate permease), lldD (encoding an L-iLDH), and lldE (encoding
      a D-iLDH). Cotranscription of lldP, lldD, and lldE in Pseudomonas aeruginosa
      strain XMG starts with the base, C, that is located 138 bp upstream of the lldP
      ATG start codon. The lldPDE operon is located adjacent to lldR (encoding an FadR
      type regulator, LldR). The gel mobility shift assays revealed that the purified
      His-tagged LldR binds to the upstream region of lldP. An XMG mutant strain that
      constitutively expresses D-iLDH and L-iLDH was found to contain a mutation in
      lldR that leads to an Ile23-to-serine substitution in the LldR protein. The
      mutated protein, LldR(M), lost its DNA-binding activity. A motif with a
      hyphenated dyad symmetry (TGGTCTTACCA) was identified as essential for the
      binding of LldR to the upstream region of lldP by using site-directed
      mutagenesis. L-Lactate and D-lactate interfered with the DNA-binding activity of
      LldR. Thus, L-iLDH and D-iLDH were expressed when the operon was induced in the
      presence of L-lactate or D-lactate.

PMID- 22408167
TI  - Orientation of Pseudomonas aeruginosa ExsA monomers bound to promoter DNA and
      base-specific contacts with the P(exoT) promoter.
AB  - ExsA is a transcriptional activator of the Pseudomonas aeruginosa type III
      secretion system (T3SS) and a member of the AraC/XylS protein family. Each of the
      10 ExsA-dependent promoter regions that define the T3SS regulon has two adjacent
      binding sites for monomeric ExsA. Whereas the promoter-proximal sites (binding
      site 1) contain highly conserved GnC and TGnnA sequences that are separated by
      ~10 bp, the promoter-distal sites (binding site 2) share no obvious sequence
      similarity to each other or to the binding site 1 consensus. In the present
      study, we used footprinting with Fe-BABE (a protein-labeling reagent that can be
      conjugated to cysteine residues) to demonstrate that the two ExsA monomers bind
      to the P(exsC), P(exsD), P(exoT), and P(pcrG) promoters in a head-to-tail
      orientation. The footprinting data further indicate that the conserved GnC and
      TGnnA sequences constitute binding site 1. When bound to site 1, the first helix
      turn-helix (HTH) motif of ExsA interacts with the conserved GnC sequence, and the
      second HTH interacts at or near the TGnnA sequences. Genetic data using the
      P(exoT) promoter indicate that residues L198 and T199 in the first HTH motif of
      ExsA contact the guanine in the GnC sequence and that residue K202, also in the
      first HTH motif, contacts the cytosine. Likewise, evidence is presented that
      residues Q248, Y250, T252, and R257 located in the second HTH motif contribute to
      the recognition of the TGnnA sequence. These combined data define interactions of
      ExsA with site 1 on the P(exoT) promoter and provide insight into the nature of
      the interactions involved in recognition of binding site 2.

PMID- 22408168
TI  - H-NS regulation of IraD and IraM antiadaptors for control of RpoS degradation.
AB  - RpoS, the master sigma factor during stationary phase and under a variety of
      stress conditions, is regulated at multiple levels, including regulated
      degradation. Degradation is dependent upon ClpXP and the RssB adaptor protein. H
      NS, a nucleoid-associated protein, affects the regulated degradation of RpoS; in
      the absence of H-NS, RpoS is stable. The mechanisms involved in this regulation
      were not known. We have found that H-NS inhibits the expression of iraD and iraM,
      the genes coding for two antiadaptor proteins that stabilize RpoS when
      overexpressed. The regulation by H-NS of iraM is independent from the previously
      demonstrated regulation by the PhoP/PhoQ two-component system. Moreover,
      differences in the behavior of several hns alleles are explained by a role for
      StpA, an H-NS-like protein, in the regulation of RpoS stability. This finding
      parallels recent observations for a role of StpA in regulation of RpoS stability
      in Salmonella.

PMID- 22408169
TI  - Identification and characterization of a lipopolysaccharide alpha,2,3
      sialyltransferase from the human pathogen Helicobacter bizzozeronii.
AB  - Terminal sialic acid in the lipopolysaccharides (LPSs) of mucosal pathogens is an
      important virulence factor. Here we report the characterization of a Helicobacter
      sialyltransferase involved in the biosynthesis of sialylated LPS in Helicobacter
      bizzozeronii, the only non-pylori gastric Helicobacter species isolated from
      humans thus far. Starting from the genome sequences of canine and human strains,
      we identified potential sialyltransferases downstream of three genes involved in
      the biosynthesis of N-acetylneuraminic acid. One of these candidates showed
      monofunctional alpha,2,3-sialyltransferase activity with a preference for N
      acetyllactosamine as a substrate. The LPSs from different strains were shown by
      SDS-PAGE and high-performance anion-exchange chromatography with pulsed
      amperometric detection (HPAEC-PAD) to contain sialic acid after neuraminidase
      treatment. The expression of this sialyltransferase and sialyl-LPS appeared to be
      a phase-variable characteristic common to both human and canine H. bizzozeronii
      strains. The sialylation site of the LPSs of two H. bizzozeronii strains was
      determined to be NeuAc-Hex-HexNAc, suggesting terminal 3'-sialyl-LacNAc.
      Moreover, serological typing revealed the possible presence of sialyl-Lewis X in
      two additional strains, indicating that H. bizzozeronii could also mimic the
      surface glycans of mammalian cells. The expression of sialyl-glycans may
      influence the adaptation process of H. bizzozeronii during the host jump from
      dogs to humans.

PMID- 22408170
TI  - The presumption of intent for organ donation: trumping patients' constitutional
      rights.

PMID- 22408171
TI  - Translational control of glucose-induced islet amyloid polypeptide production in
      pancreatic islets.
AB  - Dysfunctional islet amyloid polypeptide (IAPP) biosynthesis and/or processing are
      thought contribute to formation of islet amyloid in type 2 diabetes. However, it
      is unclear how normal pro-IAPP biosynthesis and processing are regulated to be
      able to define such dysfunction. Here, it was found that acute exposure to high
      glucose concentrations coordinately regulated the biosynthesis of pro-IAPP,
      proinsulin, and its proprotein convertase PC1/3 in normal isolated rat islets,
      without affecting their respective mRNA levels. Pro-7B2 biosynthesis, like that
      of pro-PC2, did not appreciably change, but this was likely due to a much higher
      expression in pancreatic alpha-cells masking glucose regulation of their
      biosynthesis in beta-cells. Biosynthesis of pro-SAAS, the putative PC1/3
      chaperone, was unaffected by glucose, consistent with its scarce expression in
      beta-cells. We conclude that translational control of pro-IAPP biosynthesis, in
      parallel to the pro-PC1/3, pro-PC2, and pro-7B2 proprotein-processing
      endopeptidases/chaperones, is the predominate mechanism to produce IAPP in islet
      beta-cells.

PMID- 22408172
TI  - Insulin-stimulated glucose uptake occurs in specialized cells within the cumulus
      oocyte complex.
AB  - The oocyte exists within the mammalian follicle surrounded by somatic cumulus
      cells. These cumulus cells metabolize the majority of the glucose within the
      cumulus oocyte complex and provide energy substrates and intermediates such as
      pyruvate to the oocyte. The insulin receptor is present in cumulus cells and
      oocytes; however, it is unknown whether insulin-stimulated glucose uptake occurs
      in either cell type. Insulin-stimulated glucose uptake is thought to be unique to
      adipocytes, skeletal and cardiac muscle, and the blastocyst. Here, we show for
      the first time that many of the components required for insulin signaling are
      present in both cumulus cells and oocytes. We performed a set of experiments on
      mouse cumulus cells and oocytes and human cumulus cells using the
      nonmetabolizable glucose analog 2-deoxy-d-glucose to measure basal and insulin
      stimulated glucose uptake. We show that insulin-stimulated glucose uptake occurs
      in both compact and expanded cumulus cells of mice, as well as in human cumulus
      cells. Oocytes, however, do not display insulin-stimulated glucose uptake.
      Insulin-stimulated glucose uptake in cumulus cells is mediated through
      phosphatidylinositol 3-kinase signaling as shown by inhibition of insulin
      stimulated glucose uptake and Akt phosphorylation with the specific
      phosphatidylinositol 3-kinase inhibitor, LY294002. To test the effect of systemic
      in vivo insulin resistance on insulin sensitivity in the cumulus cell, cumulus
      cells from high fat-fed, insulin-resistant mice and women with polycystic ovary
      syndrome were examined. Both sets of cells displayed blunted insulin-stimulated
      glucose uptake. Our studies identify another tissue that, through a classical
      insulin-signaling pathway, demonstrates insulin-stimulated glucose uptake.
      Moreover, these findings suggest insulin resistance occurs in these cells under
      conditions of systemic insulin resistance.

PMID- 22408173
TI  - Vitamin D deficiency exacerbates experimental stroke injury and dysregulates
      ischemia-induced inflammation in adult rats.
AB  - Vitamin D deficiency (VDD) is widespread and considered a risk factor for
      cardiovascular disease and stroke. Low vitamin D levels are predictive for stroke
      and more fatal strokes in humans, whereas vitamin D supplements are associated
      with decreased risk of all-cause mortality. Because VDD occurs with other
      comorbid conditions that are also independent risk factors for stroke, this study
      examined the specific effect of VDD on stroke severity in rats. Adult female rats
      were fed control or VDD diet for 8 wk and were subject to middle cerebral artery
      occlusion thereafter. The VDD diet reduced circulating vitamin D levels to one
      fifth (22%) of that observed in rats fed control chow. Cortical and striatal
      infarct volumes in animals fed VDD diet were significantly larger, and
      sensorimotor behavioral testing indicated that VDD animals had more severe
      poststroke behavioral impairment than controls. VDD animals were also found to
      have significantly lower levels of the neuroprotective hormone IGF-I in plasma
      and the ischemic hemisphere. Cytokine analysis indicated that VDD significantly
      reduced IL-1alpha, IL-1beta, IL-2, IL-4, IFN-gamma, and IL-10 expression in
      ischemic brain tissue. However, ischemia-induced IL-6 up-regulation was
      significantly higher in VDD animals. In a separate experiment, the therapeutic
      potential of acute vitamin D treatments was evaluated, where animals received
      vitamin D injections 4 h after stroke and every 24 h thereafter. Acute vitamin D
      treatment did not improve infarct volume or behavioral performance. Our data
      indicate that VDD exacerbates stroke severity, involving both a dysregulation of
      the inflammatory response as well as suppression of known neuroprotectants such
      as IGF-I.

PMID- 22408175
TI  - The placenta, a transducer linking maternal nutrition to adult disease in the
      offspring?

PMID- 22408174
TI  - Effects of leptin and melanocortin signaling interactions on pubertal development
      and reproduction.
AB  - Leptin and melanocortin signaling control ingestive behavior, energy balance, and
      substrate utilization, but only leptin signaling defects cause hypothalamic
      hypogonadism and infertility. Although GnRH neurons do not express leptin
      receptors, leptin influences GnRH neuron activity via regulation of immediate
      downstream mediators including the neuropeptides neuropeptide Y and the
      melanocortin agonist and antagonist, alpha-MSH, agouti-related peptide,
      respectively. Here we show that modulation of melanocortin signaling in female
      db/db mice through ablation of agouti-related peptide, or heterozygosity of
      melanocortin 4 receptor, restores the timing of pubertal onset, fertility, and
      lactation. Additionally, melanocortin 4 receptor activation increases action
      potential firing and induces c-Fos expression in GnRH neurons, providing further
      evidence that melanocortin signaling influences GnRH neuron activity. These
      studies thus establish melanocortin signaling as an important component in the
      leptin-mediated regulation of GnRH neuron activity, initiation of puberty and
      fertility.

PMID- 22408176
TI  - Lipocalin 2: a "sexy" adipokine that regulates 17beta-estradiol and obesity.

PMID- 22408177
TI  - The protective side of the mineralocorticoid receptor.

PMID- 22408178
TI  - Infertility in the Southern White Rhino: is diet the source of the problem?

PMID- 22408179
TI  - Tacking toward reconciliation on Tacr3/TACR3 mutations.

PMID- 22408180
TI  - Metabolism of the preimplantation embryo: 40 years on.
AB  - This review considers how our understanding of preimplantation embryo metabolism
      has progressed since the pioneering work on this topic in the late 1960s and
      early 1970s. Research has been stimulated by a desire to understand how metabolic
      events contribute to the development of the zygote into the blastocyst, the need
      for biomarkers of embryo health with which to improve the success of assisted
      conception technologies, and latterly by the 'Developmental Origins of Health and
      Disease' (DOHaD) concept. However, arguably, progress has not been as great as it
      might have been due to methodological difficulties in working with tiny amounts
      of tissue and the low priority assigned to fundamental research on fertility and
      infertility, with developments driven more by technical than scientific advances.
      Nevertheless, considerable progress has been made in defining the roles of the
      traditional nutrients: pyruvate, glucose, lactate, and amino acids; originally
      considered as energy sources and biosynthetic precursors, but now recognized as
      having multiple, overlapping functions. Other nutrients; notably lipids, are
      beginning to attract the attention they deserve. The pivotal role of mitochondria
      in early embryo development and the DOHaD concept, and in providing a cellular
      focus for metabolic events is now recognized. Some unifying ideas are discussed;
      namely 'stress-response models' and the 'quiet embryo hypothesis'; the latter
      aiming to relate the metabolism of individual preimplantation embryos to their
      subsequent viability. The review concludes by updating the state of knowledge of
      preimplantation embryo metabolism in the early 1970s and listing some future
      research questions.

PMID- 22408181
TI  - Transcriptome-wide analysis of small RNA expression in early zebrafish
      development.
AB  - During early vertebrate development, a large number of noncoding RNAs are
      maternally inherited or expressed upon activation of zygotic transcription. The
      exact identity, expression levels, and function for most of these noncoding RNAs
      remain largely unknown. miRNAs (microRNAs) and piRNAs (piwi-interacting RNAs) are
      two classes of small noncoding RNAs that play important roles in gene regulation
      during early embryonic development. Here, we utilized next-generation sequencing
      technology to determine temporal expression patterns for both miRNAs and piRNAs
      during four distinct stages of early vertebrate development using zebrafish as a
      model system. For miRNAs, the expression patterns for 198 known miRNAs within 122
      different miRNA families and eight novel miRNAs were determined. Significant
      sequence variation was observed at the 5' and 3'ends of miRNAs, with most extra
      nucleotides added at the 3' end in a nontemplate directed manner. For the miR-430
      family, the addition of adenosine and uracil residues is developmentally
      regulated and may play a role in miRNA stability during the maternal zygotic
      transition. Similar modification at the 3' ends of a large number of miRNAs
      suggests widespread regulation of stability during early development. Beside
      miRNAs, we also identified a large and unexpectedly diverse set of piRNAs
      expressed during early development.

PMID- 22408184
TI  - Methane production by red-necked wallabies (Macropus rufogriseus).
AB  - The claimed low production of CH(4) by kangaroos and marsupials in general has
      been questioned because of a lack of data. The extent of their CH(4) production
      is of interest both from the point of view of discussing meat production of
      marsupials and as a basis for developing methods to reduce CH(4) production from
      ruminants. In the present experiment, the CH(4) production of 8 red-necked
      wallabies (Macropus rufogriseus) was measured of which 4 were fed 2 different
      diets in an open-circuit respiration chamber. These results were compared with a
      newly developed, inexpensive, and simple method that does not influence the
      behavior of the animal, and where the ratio between CH(4) and CO(2) is measured
      and used together with the calculated CO(2) to quantify the CH(4) production. The
      experiment demonstrated that the wallabies produce CH(4). However, the amount of
      CH(4) produced by these wallabies was between 1.6 and 2.5 L/d equivalent to 1.6
      and 2.5% of GE or 2.2% and 3.5% of DE intake and 0.22 L/BW, kg(0.75). This is
      between 25 and 33% of what can be expected from ruminants fed the same diet.
      Based on the uneven release of CH(4) with time, it is most likely that the CH(4)
      is excreted through flatulence and not through breathing as is seen in ruminants.
      The experiments also showed that a reasonably accurate determination of the CH(4)
      production of a group of animals can be obtained by simply measuring the
      CH(4)/CO(2) ratio over a limited time span. This may represent the situation in a
      natural setting better than measurements in a respiration chamber. It was found
      that the CH(4)/CO(2) ratio in itself represents a reasonable prediction of the
      proportion of feed GE that is lost as CH(4), and that this method offers new
      opportunities for CH(4) measurements on a large number of animals.

PMID- 22408182
TI  - CEF1/CDC5 alleles modulate transitions between catalytic conformations of the
      spliceosome.
AB  - Conformational change within the spliceosome is required between the first and
      second catalytic steps of pre-mRNA splicing. A prior genetic screen for
      suppressors of an intron mutant that stalls between the two steps yielded both
      prp8 and non-prp8 alleles that suppressed second-step splicing defects. We have
      now identified the strongest non-prp8 suppressors as alleles of the NTC (Prp19
      complex) component, CEF1. These cef1 alleles generally suppress second-step
      defects caused by a variety of intron mutations, mutations in U6 snRNA, or
      deletion of the second-step protein factor Prp17, and they can activate
      alternative 3' splice sites. Genetic and functional interactions between cef1 and
      prp8 alleles suggest that they modulate the same event(s) in the first-to-second
      step transition, most likely by stabilization of the second-step spliceosome; in
      contrast, alleles of U6 snRNA that also alter this transition modulate a distinct
      event, most likely by stabilization of the first-step spliceosome. These results
      implicate a myb-like domain of Cef1/CDC5 in interactions that modulate
      conformational states of the spliceosome and suggest that alteration of these
      events affects splice site use, resulting in alternative splicing-like patterns
      in yeast.

PMID- 22408185
TI  - Vertical distributions of 137Cs, 40K, 232Th and 226Ra in soil samples from
      Istanbul and its environs, Turkey.
AB  - Determining the distribution of natural and artificial radionuclides in soil
      profiles as well as the surface layer of the soil is necessary due to the fact
      that radionuclides can enter the food chain from deeper soil layers and also
      contaminate ground water. In the current study, the activity-depth profiles of
      (137)Cs were determined in soil samples from 20 sites in and around the city of
      Istanbul. Naturally  occurring radionuclides were determined at 12 of the
      locations. Uncultivated soil samples were taken in six horizontal layers at each
      location. Activity concentrations were measured with a gamma spectrometer. The
      impacts of texture, organic matter and pH of the soil on the vertical
      distribution of the radionuclides were also studied. The average and standard
      deviations of (137)Cs and (40)K activity concentrations in soil at a depth of 5
      cm were found to be 16.46+/-14.71 and 450.2+/-239.1 Bq kg(-1), respectively. The
      activity concentrations of (40)K, (232)Th and (226)Ra were distributed uniformly
      with regard to soil depth. The depth distribution of (137)Cs generally fitted a
      linear function. The study revealed that >20 y after the Chernobyl disaster of
      1986, 55 % of (137)Cs still remains in the upper 10 cm of soil in the Istanbul
      environment.

PMID- 22408186
TI  - Plant responsiveness to root-root communication of stress cues.
AB  - BACKGROUND AND AIMS: Phenotypic plasticity is based on the organism's ability to
      perceive, integrate and respond to multiple signals and cues informative of
      environmental opportunities and perils. A growing body of evidence demonstrates
      that plants are able to adapt to imminent threats by perceiving cues emitted from
      their damaged neighbours. Here, the hypothesis was tested that unstressed plants
      are able to perceive and respond to stress cues emitted from their drought- and
      osmotically stressed neighbours and to induce stress responses in additional
      unstressed plants. METHODS: Split-root Pisum sativum, Cynodon dactylon, Digitaria
      sanguinalis and Stenotaphrum secundatum plants were subjected to osmotic stress
      or drought while sharing one of their rooting volumes with an unstressed
      neighbour, which in turn shared its other rooting volume with additional
      unstressed neighbours. Following the kinetics of stomatal aperture allowed
      testing for stress responses in both the stressed plants and their unstressed
      neighbours. KEY RESULTS: In both P. sativum plants and the three wild clonal
      grasses, infliction of osmotic stress or drought caused stomatal closure in both
      the stressed plants and in their unstressed neighbours. While both continuous
      osmotic stress and drought induced prolonged stomatal closure and limited
      acclimation in stressed plants, their unstressed neighbours habituated to the
      stress cues and opened their stomata 3-24 h after the beginning of stress
      induction. CONCLUSIONS: The results demonstrate a novel type of plant
      communication, by which plants might be able to increase their readiness to
      probable future osmotic and drought stresses. Further work is underway to
      decipher the identity and mode of operation of the involved communication vectors
      and to assess the potential ecological costs and benefits of emitting and
      perceiving drought and osmotic stress cues under various ecological scenarios.

PMID- 22408187
TI  - Defining the risk of toxicity in phase I oncology trials of novel molecularly
      targeted agents: a single centre experience.
AB  - BACKGROUND: This study defined the risk of serious toxicity in phase I trials of
      molecularly targeted agents (MTA). PATIENTS AND METHODS: A retrospective analysis
      of toxicity data from patients treated in phase I trials of MTAs was carried out
      to define the rate of treatment-related grade 3/4 toxic effects, deaths and risk
      factors associated with grade 3 or more toxicity. RESULTS: Data from 687 patients
      [median age, 59.1 years (range 12.5-85.5)] treated in 36 trials were analysed.
      Two hundred and eleven patients were of Eastern Cooperative Oncology Group
      performance status (PS) zero, 432 of PS one, 38 of PS two and 6 unknown. The rate
      of grade 3 and 4 events was 14.1% (n=97) and 1.9% (n=13), respectively. Twenty
      four percent of events were gastrointestinal, 22% constitutional and 20%
      metabolic. PS two was associated with a higher risk of toxicity [odds ratio (OR),
      2.6; 95% confidence interval (CI) 1.1-6.1; P=0.032] as was receiving >100% of
      maximum tolerated dose or maximum administered dose (OR 2.5; CI 1.6-3.9;
      P<0.001). Mortality rate was 0.43% (n=3). CONCLUSIONS: Therapy with novel MTAs in
      phase I trials is associated with a moderate risk of significant toxicity. This
      appears less than in phase I studies involving cytotoxic agents, particularly in
      relation to grade 4 toxicity. The risk of death is low.

PMID- 22408188
TI  - School children's backpacks, back pain and back pathologies.
AB  - OBJECTIVE: To investigate whether backpack weight is associated with back pain
      and back pathology in school children. DESIGN: Cross-sectional study. SETTING:
      Schools in Northern Galicia, Spain. PATIENTS: All children aged 12-17.
      INTERVENTIONS: Backpack weight along with body mass index, age and gender. MAIN
      OUTCOME MEASURES: Back pain and back pathology. RESULTS: 1403 school children
      were analysed. Of these, 61.4% had backpacks exceeding 10% of their body weight.
      Those carrying the heaviest backpacks had a 50% higher risk of back pain (OR 1.50
      CI 95% 1.06 to 2.12) and a 42% higher risk of back pathology, although this last
      result was not statistically significant (OR 1.42 CI 95% 0.86 to 2.32). Girls
      presented a higher risk of back pain compared with boys. CONCLUSIONS: Carrying
      backpacks increases the risk of back pain and possibly the risk of back
      pathology. The prevalence of school children carrying heavy backpacks is
      extremely high. Preventive and educational activities should be implemented in
      this age group.

PMID- 22408189
TI  - Not seeing the genomes for the DNA.
AB  - This Short Communication highlights the diversity of 'secondary' genome data
      (like mitochondrial and plastid genomes) that can be gleaned from next-generation
      sequencing projects, and encourages researchers to be mindful that these data are
      often as informative and useful as the 'primary' genome data.

PMID- 22408190
TI  - Class-imbalanced classifiers for high-dimensional data.
AB  - A class-imbalanced classifier is a decision rule to predict the class membership
      of new samples from an available data set where the class sizes differ
      considerably. When the class sizes are very different, most standard
      classification algorithms may favor the larger (majority) class resulting in poor
      accuracy in the minority class prediction. A class-imbalanced classifier
      typically modifies a standard classifier by a correction strategy or by
      incorporating a new strategy in the training phase to account for differential
      class sizes. This article reviews and evaluates some most important methods for
      class prediction of high-dimensional imbalanced data. The evaluation addresses
      the fundamental issues of the class-imbalanced classification problem: imbalance
      ratio, small disjuncts and overlap complexity, lack of data and feature
      selection. Four class-imbalanced classifiers are considered. The four classifiers
      include three standard classification algorithms each coupled with an ensemble
      correction strategy and one support vector machines (SVM)-based correction
      classifier. The three algorithms are (i) diagonal linear discriminant analysis
      (DLDA), (ii) random forests (RFs) and (ii) SVMs. The SVM-based correction
      classifier is SVM threshold adjustment (SVM-THR). A Monte-Carlo simulation and
      five genomic data sets were used to illustrate the analysis and address the
      issues. The SVM-ensemble classifier appears to perform the best when the class
      imbalance is not too severe. The SVM-THR performs well if the imbalance is severe
      and predictors are highly correlated. The DLDA with a feature selection can
      perform well without using the ensemble correction.

PMID- 22408191
TI  - The automatic annotation of bacterial genomes.
AB  - With the development of ultra-high-throughput technologies, the cost of
      sequencing bacterial genomes has been vastly reduced. As more genomes are
      sequenced, less time can be spent manually annotating those genomes, resulting in
      an increased reliance on automatic annotation pipelines. However, automatic
      pipelines can produce inaccurate genome annotation and their results often
      require manual curation. Here, we discuss the automatic and manual annotation of
      bacterial genomes, identify common problems introduced by the current genome
      annotation process and suggests potential solutions.

PMID- 22408192
TI  - SMURFLite: combining simplified Markov random fields with simulated evolution
      improves remote homology detection for beta-structural proteins into the twilight
      zone.
AB  - MOTIVATION: One of the most successful methods to date for recognizing protein
      sequences that are evolutionarily related has been profile hidden Markov models
      (HMMs). However, these models do not capture pairwise statistical preferences of
      residues that are hydrogen bonded in beta sheets. These dependencies have been
      partially captured in the HMM setting by simulated evolution in the training
      phase and can be fully captured by Markov random fields (MRFs). However, the MRFs
      can be computationally prohibitive when beta strands are interleaved in complex
      topologies. We introduce SMURFLite, a method that combines both simplified MRFs
      and simulated evolution to substantially improve remote homology detection for
      beta structures. Unlike previous MRF-based methods, SMURFLite is computationally
      feasible on any beta-structural motif. RESULTS: We test SMURFLite on all
      propeller and barrel folds in the mainly-beta class of the SCOP hierarchy in
      stringent cross-validation experiments. We show a mean 26% (median 16%)
      improvement in area under curve (AUC) for beta-structural motif recognition as
      compared with HMMER (a well-known HMM method) and a mean 33% (median 19%)
      improvement as compared with RAPTOR (a well-known threading method) and even a
      mean 18% (median 10%) improvement in AUC over HHPred (a profile-profile HMM
      method), despite HHpred's use of extensive additional training data. We
      demonstrate SMURFLite's ability to scale to whole genomes by running a SMURFLite
      library of 207 beta-structural SCOP superfamilies against the entire genome of
      Thermotoga maritima, and make over a 100 new fold predictions. Availability and
      implementaion: A webserver that runs SMURFLite is available at:
      http://smurf.cs.tufts.edu/smurflite/

PMID- 22408193
TI  - Defining and providing robust controls for microRNA prediction.
AB  - MOTIVATION: microRNAs are short non-coding RNAs that regulate gene expression by
      inhibiting target mRNA genes. Next-generation sequencing combined with
      bioinformatics analyses provide an opportunity to predict numerous novel miRNAs.
      The efficiency of these predictions relies on the set of positive and negative
      controls used. We demonstrate that commonly used positive and negative controls
      may be unreliable and provide a rational methodology with which to replace them.

PMID- 22408194
TI  - Deriving transcriptional programs and functional processes from gene expression
      databases.
AB  - MOTIVATION: A system-wide approach to revealing the underlying molecular state of
      a cell is a long-standing biological challenge. Developed over the last decade,
      gene expression profiles possess the characteristics of such an assay. They have
      the capacity to reveal both underlying molecular events as well as broader
      phenotypes such as clinical outcomes. To interpret these profiles, many gene sets
      have been developed that characterize biological processes. However, the full
      potential of these gene sets has not yet been achieved. Since the advent of gene
      expression databases, many have posited that they can reveal properties of
      activities that are not evident from individual datasets, analogous to how the
      expression of a single gene generally cannot reveal the activation of a
      biological process. RESULTS: To address this issue, we have developed a high
      throughput method to mine gene expression databases for the regulation of gene
      sets. Given a set of genes, we scored it against each gene expression dataset by
      looking for enrichment of co-regulated genes relative to an empirical null
      distribution. After validating the method, we applied it to address two
      biological problems. First, we deciphered the E2F transcriptional network. We
      confirmed that true transcriptional targets exhibit a distinct regulatory profile
      across a database. Second, we leveraged the patterns of regulation across a
      database of gene sets to produce an automatically generated catalog of biological
      processes. These demonstrations revealed the power of a global analysis of the
      data contained within gene expression databases, and the potential for using them
      to address biological questions.

PMID- 22408195
TI  - Nitric oxide in primary ciliary dyskinesia.
AB  - Nitric oxide is continually synthesised in the respiratory epithelium and is
      upregulated in response to infection or inflammation. Primary ciliary dyskinesia
      (PCD) is characterised by recurrent sinopulmonary infections due to impaired
      mucociliary clearance. Despite chronic infections, nasal nitric oxide in such
      patients is markedly reduced and is used as a screening test for this condition.
      These low levels were first described >15 yrs ago but the underlying mechanisms
      have yet to be fully elucidated. We review epithelial nitric oxide synthesis,
      release and measurement in the upper airways with particular reference to PCD.
      The key hypotheses that have been proposed to explain the low nitric oxide levels
      in this condition are explored and the potential benefits of augmenting airway
      nitric oxide levels are considered. Further work in these patients clarifying
      both whether the respiratory epithelium is able to biosynthesise normal levels of
      nitric oxide and the role played by abnormalities in the anatomy of the paranasal
      sinuses is essential. While nitric oxide augmentation is unlikely to be
      beneficial in common PCD phenotypes, it has potential in the treatment of
      secondary dyskinesias and may also improve treatment of bacterial infections,
      particularly where biofilms are implicated.

PMID- 22408196
TI  - Clinical highlights from the 2011 ERS Congress in Amsterdam.
AB  - This article reports on selected papers pertinent to the most important clinical
      problems in the field of respiratory medicine. Expert authors from the Clinical
      Assembly of the European Respiratory Society (ERS) have selected updated reports
      related to presentations given at the 2011 ERS Annual Congress, which was held in
      Amsterdam (the Netherlands) and attended by more than 20,000 participants. The
      hot topics and selected abstracts from the scientific groups of the Clinical
      Assembly are discussed here in the context of recent literature.

PMID- 22408197
TI  - Dose response of continuous positive airway pressure on nasal symptoms,
      obstruction and inflammation in vivo and in vitro.
AB  - Obstructive sleep apnoea is a common condition associated with cardiovascular
      risk. Continuous positive airway pressure (CPAP) is an effective treatment but is
      associated with nasal side-effects, which hinder compliance and may result from
      inflammation. We investigated whether CPAP was pro-inflammatory to human subjects
      in vivo, and to cultured bronchial epithelial cells in vitro. In vivo, we further
      investigated whether induction of nasal inflammation was associated with the
      development of systemic inflammation, nasal symptoms and changes in nasal
      mucociliary clearance. In vitro, CPAP resulted in cytokine release from cultured
      BEAS-2B cells in a time- and dose (pressure)-dependent manner. In vivo, CPAP
      resulted in dose-dependent upregulation of nasal inflammatory markers associated
      with the development of nasal symptoms, and reduced mucociliary clearance. CPAP
      also upregulated selected markers of systemic inflammation. CPAP results in dose
      dependent release of inflammatory cytokines from human epithelial cells in vitro
      and in vivo. In vivo responses were associated with systemic inflammation,
      reductions in nasal mucociliary function and the development of nasal symptoms.
      This emphasises the need for novel strategies to reduce nasal inflammation and
      therefore aid compliance.

PMID- 22408198
TI  - Exercise training reverses exertional oscillatory ventilation in heart failure
      patients.
AB  - Exertional oscillatory ventilation (EOV) is an ominous prognostic sign in chronic
      heart failure (CHF), but little is known about the success of specific
      therapeutic interventions. Our aim was to study the impact of an exercise
      training on exercise capacity and cardiopulmonary adaptation in stable CHF
      patients with left ventricular systolic dysfunction and EOV. 96 stable CHF
      patients with EOV were included in a retrospective analysis (52 training versus
      44 controls). EOV was defined as follows: 1) three or more oscillatory
      fluctuations in minute ventilation (V'(E)) during exercise; 2) regular
      oscillations; and 3) minimal average ventilation amplitude >=5 L. EOV disappeared
      in 37 (71.2%) out of 52 patients after training, but only in one (2.3%) out of 44
      without training (p<0.001). The decrease of EOV amplitude correlated with changes
      in end-tidal carbon dioxide tension (r= -0.60, p<0.001) at the respiratory
      compensation point and V'(E)/carbon dioxide production (V'(CO(2))) slope (r=0.50,
      p<0.001). Training significantly improved resting values of respiratory frequency
      (f(R)), V'(E), tidal volume (V(T)) and V'(E)/V'(CO(2)) ratio. During exercise,
      V'(E) and V(T) reached significantly higher values at the peak, while f(R) and
      V'(E)/V'(CO(2)) ratio were significantly lower at submaximal exercise. No change
      was noted in the control group. Exercise training leads to a significant decrease
      of EOV and improves ventilatory efficiency in patients with stable CHF.

PMID- 22408199
TI  - Does oxidative stress modulate limb muscle atrophy in severe COPD patients?
AB  - Oxidative stress may differentially regulate protein loss within peripheral
      muscles of severe chronic obstructive pulmonary disease (COPD) patients
      exhibiting different body composition. Oxidation levels of proteins, myosin heavy
      chain (MyHC) and myonuclei, superoxide anion, antioxidants, actin, creatine
      kinase, carbonic anhydrase-3, ubiquitin-proteasome system, redox-signalling
      pathways, inflammation and muscle structure, and damage were quantified in limb
      muscles of severe COPD patients with and without muscle wasting, and in sedentary
      controls. Compared with controls, in the quadriceps of muscle-wasted COPD
      patients, levels of protein carbonylation, oxidation of MyHC and myonuclei,
      superoxide anion production, superoxide dismutase, total protein ubiquinitation,
      E2(14k), atrogin-1, FoxO1 and p65 were higher, while content of MyHC, creatine
      kinase, carbonic anhydrase-3, myogenin, and fast-twitch fibre size were
      decreased. Importantly, in nonwasted COPD patients, where MyHC was more oxidised
      than in controls, its content was preserved. Muscle inflammation and glutathione
      levels did not differ between patients and controls. In all patients, muscle
      structure abnormalities were increased, while muscle force and exercise capacity
      were reduced. In severe COPD, while muscle oxidative stress increases regardless
      of their body composition, protein ubiquitination and loss of MyHC were enhanced
      only in patients exhibiting muscle atrophy. Oxidative stress does not seem to
      directly modulate muscle protein loss in these patients.

PMID- 22408200
TI  - The mechanism of deep inspiration-induced bronchoprotection: evidence from a
      mouse model.
AB  - In healthy individuals, deep inspirations (DIs) taken prior to a bronchial
      challenge reduce the bronchoconstrictor response, which is termed
      "bronchoprotection". The mechanism(s) of DI-induced bronchoprotection is unclear.
      The forced oscillation technique was used to assess the effect of prior DI on
      subsequent bronchoconstriction to methacholine (MCh) in BALB/c mice. We assessed
      likely mechanisms for the bronchoprotective effects of DI including reduced
      airway narrowing (from changes in airway resistance) and/or closure (changes in
      tissue elastance) and enhanced bronchodilation to a subsequent DI (% reversal in
      airway narrowing). DI prior to MCh challenge: 1) did not reduce but instead
      enhanced airway narrowing (p<0.05); 2) increased ventilation heterogeneity
      (p<0.05); 3) enhanced the subsequent bronchodilatory response to DI (p<0.05); and
      4) reduced tissue elastance (p<0.05), suggesting opening of closed airways or
      alveoli units. Our findings suggest that DI prior to MCh challenge may elicit a
      series of changes, some of which are beneficial to respiratory function (enhanced
      bronchodilation), while others place greater load on the system (enhanced
      bronchoconstriction and ventilation heterogeneity). It is proposed that the
      relative magnitudes of these opposing physiological and mechanical effects will
      determine the net effect on respiratory function in health and disease.

PMID- 22408201
TI  - Macrolide effects on the prevention of COPD exacerbations.
AB  - The number of senile patients with chronic obstructive pulmonary disease (COPD)
      has recently increased due to an increase in life expectancy, the habit of
      smoking and the inhalation of toxic particles. COPD exacerbations are caused by
      airway bacterial and viral infections, as well as the inhalation of oxidative
      substrates. COPD exacerbations are associated with the worsening of symptoms and
      quality of life, as well as an increased mortality rate. Several drugs, including
      long-acting anti-cholinergic agents, long-acting beta(2)-agonists and inhaled
      corticosteroids, have been developed to improve symptoms in COPD patients and to
      prevent COPD exacerbations. Treatment with macrolide antibiotics has been
      reported to prevent COPD exacerbations and improve patient quality of life and
      symptoms, especially in those patients who have frequent exacerbations. In
      addition to their antimicrobial effects, macrolides have a variety of
      physiological functions, such as anti-inflammatory and anti-viral effects,
      reduced sputum production, the inhibition of biofilm formation and the inhibition
      of bacterial virulence factor production. These unique activities may relate to
      the prevention of exacerbations in COPD patients who receive macrolides. Herein,
      we review the inhibitory effects that macrolides have on COPD exacerbations and
      explore the possible mechanisms of these effects.

PMID- 22408202
TI  - Factors influencing the decline in lung density in a Danish lung cancer screening
      cohort.
AB  - Lung cancer screening trials provide an opportunity to study the natural history
      of emphysema by using computed tomography (CT) lung density as a surrogate
      parameter. In the Danish Lung Cancer Screening Trial, 2,052 participants were
      included. At screening rounds, smoking habits were recorded and spirometry was
      performed. CT lung density was measured as the volume-adjusted 15th percentile
      density (PD15). A mixed effects model was used with former smoking males with <30
      pack-yrs and without airflow obstruction (AFO) at entry as a reference group. At
      study entry, 893 (44%) participants had AFO. For the reference group, PD15 was
      72.6 g.L(-1) with an annual decline of -0.33 g.L(-1). Female sex and current
      smoking increased PD15 at baseline, 17.3 g.L(-1) (p<0.001) and 10 g.L(-1)
      (p<0.001), respectively; and both increased the annual decline in PD15 (female: 
      0.3 g.L(-1); current smoking: -0.4 g.L(-1)). The presence and severity of AFO was
      a strong predictor of low PD15 at baseline (Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) I: -1.4 g.L(-1); GOLD II: -6.3 g.L(-1); GOLD III:
      -17 g.L(-1)) and of increased annual decline in PD15 (GOLD I: -0.2 g.L(-1); GOLD
      II: -0.5 g.L(-1); GOLD III: -0.5 g.L(-1)). Female sex, active smoking and the
      presence of AFO are associated with accelerated decline in lung density.

PMID- 22408203
TI  - Severity assessment of healthcare-associated pneumonia and pneumonia in
      immunosuppression.
AB  - The study compares the ability of the PSI (pneumonia severity index), CURB-65
      (confusion, urea >7 mol.L(-1), respiratory rate >= 30 breaths.min(-1), blood
      pressure <90 mmHg systolic or <= 60 mmHg diastolic, and age >= 65 yrs), CURB and
      CRB-65 scales and the Severe Community-Acquired Pneumonia (SCAP) score to predict
      30-day mortality in healthcare-associated pneumonia (HCAP) patients, and analyses
      differences in the demographics, aetiology and outcomes of community-acquired
      pneumonia (CAP), HCAP and pneumonia in immunocompromised patients. 629
      consecutive patients admitted to a tertiary care university hospital were
      prospectively categorised as having CAP (n=322) or HCAP (n=307), and the HCAP
      patients were further sub-divided into those who were immunocompromised (n=219)
      or immunocompetent (n=88). The 30-day mortality rate was 9.0% in the CAP group
      and 24.1% in the HCAP group. In the HCAP group, the PSI and SCAP scores had
      similar prognostic power (area under the curve (AUC) of 0.68 and 0.67,
      respectively) and performed better than the CURB-65 score (AUC <=0.62). Among the
      immunocompetent HCAP patients, the PSI and CURB-65 scores were more sensitive
      than the others at every threshold, whereas SCAP was more specific than both of
      these. In the immunocompromised group, the PSI was highly sensitive but poorly
      specific at all thresholds. Our results suggest that prognostic tools should be
      designed for subsets of HCAP patients.

PMID- 22408204
TI  - Clinical analysis of 76 patients pathologically diagnosed with pulmonary
      cryptococcosis.
AB  - The aim of the present study was to investigate the clinical characteristics of
      pulmonary cryptococcosis patients in China, with analysis of immunocompetent and
      immunocompromised subjects. We performed a retrospective review of 76 patients
      diagnosed with tissue-confirmed pulmonary cryptococcosis at the Shanghai
      Pulmonary Hospital (Shanghai, China) during a 10-yr period (2001-2010). Of 76
      patients (54 males and 22 females), 41 (53.95%) were immunocompetent and 35 out
      of the 41 were asymptomatic. Approximately 80% of the patients had histories
      suspicious of environmental fungal exposure. Radiological (computed tomography)
      findings showed predominantly peripheral findings (85.53%, 65 out of 76 patients)
      including nodular masses (55.26%, 42 out of 76), pneumonic infiltrates (23.68%,
      18 out of 76) and mixed type (21.05%, 16 out of 76). 43.42% (33 out of 76) were
      initially misdiagnosed, often as cancer by false-positive (18)F
      fluorodeoxyglucose positron emission tomography ((18)FDG-PET) (28 out of 46
      cases). 51 patients received antifungal therapy, 25 patients were clinically
      observed without treatment. As of December 31, 2010, 71 cases showed total
      recovery and four cases showed improvement (efficacy rate of 98.68%, 75 out of
      76). One HIV-positive case died of cryptococcal meningitis. Incidence of
      pulmonary cryptococcosis in China may be related to environmental fungal
      exposures. Most presented as asymptomatic peripheral lung lesions. False-positive
      (18)FDG-PET examinations often lead to initial clinical misdiagnosis of cancer.
      Unlike immunocompromised or clinically symptomatic patients, all immunocompetent
      patients had a good response, either to fluconazole monotherapy or observation,
      with a tendency for spontaneous remissions in the asymptomatic immunocompetent
      subjects.

PMID- 22408205
TI  - Cured meat consumption increases risk of readmission in COPD patients.
AB  - Recent studies have shown that a high dietary intake of cured meat increases the
      risk of chronic obstructive pulmonary disease (COPD) development. However, its
      potential effects on COPD evolution have not been tested. We aimed to assess the
      association between dietary intake of cured meat and risk of COPD readmission in
      COPD patients. 274 COPD patients were recruited during their first COPD admission
      between 2004 and 2006, provided information on dietary intake of cured meat
      during the previous 2 yrs, and were followed until December 31, 2007 (median
      follow-up 2.6 yrs). Associations between cured meat intake and COPD admissions
      were assessed using parametric regression survival-time models. Mean +/- SD age
      was 68 +/- 8 yrs, 93% of patients were male, 42% were current smokers, mean post
      bronchodilator forced expiratory volume in 1 s (FEV(1)) was 53 +/- 16% predicted,
      and median cured meat intake was 23 g . day(-1). After adjusting for age, FEV(1),
      and total caloric intake, high cured meat intake (more than median value)
      increased the risk of COPD readmission (adjusted HR 2.02, 95% CI 1.31-3.12;
      p=0.001). High cured meat consumption increases the risk of COPD readmission in
      COPD patients. The assessment of the effectiveness of healthy diet advice should
      be considered in the future.

PMID- 22408206
TI  - High-intensity knee extensor training restores skeletal muscle function in COPD
      patients.
AB  - Improving reduced skeletal muscle function is important for optimising exercise
      tolerance and quality of life in chronic obstructive pulmonary disease (COPD)
      patients. By applying high-intensity training to a small muscle group, we
      hypothesised a normalisation of muscle function. Seven patients with COPD
      performed 6 weeks (3 days.week(-1)) of high-intensity interval aerobic knee
      extensor exercise training. Five age-matched healthy individuals served as a
      reference group. Muscle oxygen uptake and mitochondrial respiration of the vastus
      lateralis muscle were measured before and after the 6-week training programme.
      Initial peak work and maximal mitochondrial respiration were reduced in COPD
      patients and improved significantly after the training programme. Peak power and
      maximal mitochondrial respiration in vastus lateralis muscle increased to the
      level of the control subjects and were mainly mediated via improved complex I
      respiration. Furthermore, when normalised to citrate synthase activity, no
      difference in maximal respiration was found either after the intervention or
      compared to controls, suggesting normal functioning mitochondrial complexes. The
      present study shows that high-intensity training of a restricted muscle group is
      highly effective in restoring skeletal muscle function in COPD patients.

PMID- 22408207
TI  - Evidence of unexpected oxidative stress in airways of adolescents born very pre
      term.
AB  - Prematurity and its main respiratory complication, bronchopulmonary dysplasia
      (BPD), are potentially associated with lifelong respiratory morbidities and/or
      lung function abnormalities. The mechanisms behind these long-term respiratory
      problems are still unclear. We assessed airway oxidative stress in adolescents
      born very pre-term (<= 32 gestational weeks) by measuring 8-isoprostane
      concentration in exhaled breath condensate (EBC). In addition, the study protocol
      included spirometry and measurement of exhaled nitric oxide fraction (F(eNO)).
      The study groups included 34 ex-pre-term adolescents with BPD, 18 ex-pre-term
      adolescents without BPD and 34 healthy controls born at term. Regardless of a
      history of BPD, the ex-premature adolescents had higher EBC 8-isoprostane levels
      (median (interquartile range) BPD 9.5 (7.3-12.2) pg.mL(-1); pre-term non-BPD 10
      (8.1-16) pg.mL(-1)) than the controls (3.2 (1.9-6.5) pg.mL(-1)) (p<0.001). Forced
      expiratory volume in 1 s was lower in the BPD group (mean +/- sd Z-score -2.1 +/-
      1.58) than in the pre-term non-BPD individuals (-1.13 +/- 1.15), who showed in
      turn significantly lower values than the controls (0.18 +/- 0.83; p<0.001).
      F(eNO) was similar in the three groups (p=0.55). Our data show that, after
      premature birth, evidence of oxidative stress in the airways may be detected into
      adolescence, suggesting that long-term respiratory abnormalities after pre-term
      birth may be associated with an ongoing airway disease and not just a stabilised
      structural lung damage.

PMID- 22408208
TI  - Airway impedance entropy and exacerbations in severe asthma.
AB  - Variability of peak flow measurements has been related to clinical outcomes in
      asthma. We hypothesised that the entropy, or information content, of airway
      impedance over short time scales may predict asthma exacerbation frequency. 66
      patients with severe asthma and 30 healthy control subjects underwent impulse
      oscillometry at baseline and following bronchodilator administration. On each
      occasion, airway impedance parameters were measured at 0.2-s intervals for 150 s,
      yielding a time series that was then subjected to sample entropy (SampEn)
      analysis. Airway impedance and SampEn of impedance were increased in asthmatic
      patients compared with healthy controls. In a logistic regression model, SampEn
      of the resistance at 5 Hz minus the resistance at 20 Hz, a marker of the
      fluctuation of the heterogeneity of airway constriction over time, was the
      variable most strongly associated with the frequent exacerbation phenotype (OR
      3.23 for every 0.1 increase in SampEn). Increased airway impedance and SampEn of
      impedance are associated with the frequent exacerbation phenotype. Prospective
      studies are required to assess their predictive value.

PMID- 22408209
TI  - Interobserver variability in the application of the novel IASLC/ATS/ERS
      classification for pulmonary adenocarcinomas.
AB  - Recently, a novel classification for pulmonary adenocarcinomas (ADCs) was
      published, the cornerstone of which is the quantification of growth patterns.
      Data on reproducibility in the routine diagnostic setting are lacking. 100
      constitutive cases of lung ADC resection specimens from our archives were
      classified independently by five pulmonary pathologists and two residents
      according to the International Association for the Study of Lung Cancer/American
      Thoracic Society/European Respiratory Society classification. The most frequent
      predominant pattern in our cohort was solid (37%), followed by acinar (35%),
      lepidic (20%), papillary (5%) and micropapillary (3%). kappa-values for the
      denomination of the predominant pattern revealed substantial agreement for
      pulmonary pathologists (kappa=0.44-0.72) and fair agreement for residents
      (kappa=0.38-0.47). Interobserver variability was significantly higher in cases
      with higher slide numbers (p=0.028) and was considerably reduced after training.
      Intraobserver variability was low (kappa=0.79-0.87). Papillary and micropapillary
      patterns were the most complicated patterns to evaluate, while evaluation of
      lepidic and solid tumour growth was straightforward. Our data imply that the
      novel classification of pulmonary ADC is applicable with acceptable interobserver
      variability if performed by specifically trained pathologists. Additional efforts
      are needed to harmonise the application of this novel and clinically important
      classification scheme of pulmonary ADC.

PMID- 22408210
TI  - A 3-year longitudinal study of sleep disordered breathing in the elderly.
AB  - Limited and controversial data exist on the natural evolution of sleep disordered
      breathing (SDB) in untreated individuals. This study examines the evolution of
      SDB over a 3-yr period in a community-based sample of elderly subjects. From the
      initial cohort of 854 healthy subjects aged mean +/- SD 68.4 +/- 0.8 yrs, 519
      untreated subjects accepted clinical and instrumental follow-up 3.6 +/- 1.6 yrs
      later. SDB was defined as a respiratory disturbance index (RDI) >15 events . h(
      1). At baseline, 202 (39%) subjects had an RDI <= 15 events . h(-1) and 317 (61%)
      had an RDI >15 events . h(-1). 3 yrs later, 280 (54%) subjects were non-SDB and
      239 (46%) had SDB. Between evaluations, the RDI decreased from 22.3 +/- 16.2 to
      16.4 +/- 13.0 events . h(-1), with a greater decrease in the number of cases with
      an RDI >30 events . h(-1) that in those with RDI >= 30 events . h(-1). In the non
      SDB group, 81% had a stable RDI and 19% increased their RDI by a mean of 13.7
      events . h(-1). In the SDB group, the RDI decreased to values <= 15 events . h(
      1) in 36.6% of cases, 63.4% still having SDB. The RDI changes did not depend on
      weight changes. In healthy elderly subjects, the prevalence and severity of SDB
      did not show a tendency toward natural worsening, some cases having improvement
      or a remission independent of weight changes. These findings also suggest that in
      the elderly, natural SDB progression is still hypothetical.

PMID- 22408211
TI  - Quality of life and behavioural adjustment in childhood hydrocephalus.
AB  - The aim of the paper is to describe parent and teacher reported behavioural
      outcomes and quality of life in childhood hydrocephalus, and to consider the
      implications for future service planning. A community sample of 235 school-aged
      children with hydrocephalus (5-16 years) were identified via a database of
      service users, held by the Scottish Spina Bifida Association. Parent and teacher
      reports of behaviour on the Strengths and Difficulties Questionnaire (SDQ), and
      parent reports of quality of life on the Paediatric Quality-of-Life Generic Core
      (PedsQL Core) and Paediatric Quality-of-Life Fatigue (PedsQL Fatigue) were
      obtained, as were reports of service use and satisfaction.  In total, 35% (n =
      76) of parents and 86% (n = 47) of teachers who were contacted participated in
      the study. Parents reported behavioural difficulties in 57% and teachers in 33%
      of children. Quality of life was significantly reduced in comparison to published
      norms. Children whose parents reported unmet needs had poorer psychosocial
      outcomes, but families rarely accessed appropriate specialist services. In
      conclusion, hydrocephalus is associated with high rates of behaviour problems and
      markedly reduced quality of life. It is important to increase professional
      awareness of psychological need in this chronic neurological condition, and to
      increase access to appropriate psychosocial services.

PMID- 22408212
TI  - Effect of a multistage ultraendurance triathlon on aldosterone, vasopressin,
      extracellular water and urine electrolytes.
AB  - Prolonged endurance exercise over several days induces increase in extracellular
      water (ECW). We aimed to investigate an association between the increase in ECW
      and the change in aldosterone and vasopressin in a multistage ultraendurance
      triathlon, the 'World Challenge Deca Iron Triathlon' with 10 Ironman triathlons
      within 10 days. Before and after each Ironman, body mass, ECW, urinary [Na(+)],
      urinary [K(+)], urinary specific gravity, urinary osmolality and aldosterone and
      vasopressin in plasma were measured. The 11 finishers completed the total
      distance of 38 km swimming, 1800 km cycling and 422 km running within 145.5
      (18.8) hours and 25 (22) minutes. ECW increased by 0.9 (1.1) L from 14.6 (1.5) L
      prerace to 15.5 (1.9) L postrace (P < 0.0001). Aldosterone increased from 70.8
      (104.5) pg/mL to 102.6 (104.6) pg/mL (P = 0.033); vasopressin remained unchanged.
      The increase in ECW was related neither to postrace aldosterone nor to postrace
      vasopressin. In conclusion, ECW and aldosterone increased after this multistage
      ultraendurance triathlon, but vasopressin did not. The increase in ECW and the
      increase in aldosterone were not associated.

PMID- 22408213
TI  - Can telehealth deliver for rural Scotland? Lessons from the Argyll & Bute
      Telehealth Programme.
AB  - Policy-makers consider telehealth to be a potential solution to delivery of care
      in rural Scotland. Telehealth can support patients in the community and may
      reduce emergency admissions to hospital. The Argyll & Bute telehealth initiative,
      which commenced in 2007, trialled home telehealth monitoring of patients with
      chronic obstructive pulmonary disease (COPD), and community- and surgery-based
      monitoring of general wellbeing and hypertension. An evaluation in 2010 assessed
      staff and patient satisfaction by questionnaire, impact on hospital and general
      practice attendance by case record review and detailed opinions on the programme
      by qualitative interviews with key staff. Home monitoring for COPD was associated
      with high levels of patient satisfaction and a reduction in hospital admissions
      and other health service contacts. Delays in implementation and some technical
      challenges compromised evaluation of the surgery and community initiatives.
      Patients and staff were generally enthusiastic but also identified potential
      barriers to development. This paper describes the implementation and outcomes of
      the initiative and identifies issues that clinicians embarking on telehealth
      programmes must consider: technical factors; governance and security; staff
      profiling and training; clinical outcomes; and scalability.

PMID- 22408214
TI  - Premature mortality in Scottish injecting drug users: a life-history approach.
AB  - In Scotland, deaths in drug users are known to be higher than in the rest of the
      UK and most of Europe. Reducing drug-related deaths is currently a national
      priority for the Scottish Government.  This study aimed to present a description
      of the life histories of a group of injecting drug users who have recently died,
      with a view to highlighting areas for further research. The Edinburgh Addiction
      Cohort study recently carried out 432 follow-up interviews between the years 2005
      and 2007. Thirty-three cases who completed this extensive interview detailing
      early life, education, employment, drug use, opiate substitution treatment,
      criminal history, mental health problems and overdose have subsequently died,
      leaving this source of rich information about their lives. The design of the
      interview used the life grid approach. Information was also compiled from full
      primary care records and General Register Office death certificates. Early life
      adversity was apparent for many cases, with a steady progression into early
      criminal behaviour and drug misuse. Poor adult life outcomes illustrated the
      lifelong damaging effects of drug injecting. Death occurred significantly earlier
      than in the general population or those living in deprived communities who did
      not use drugs. In conclusion, a clearer understanding of the life histories of
      problem drug users would be advantageous for health-care professionals and policy
      makers. More qualitative research studies are needed to highlight areas which
      might require early intervention and also complement the existing secondary data
      studies.

PMID- 22408215
TI  - Should rheumatologists be managing fibromyalgia?
AB  - Fibromyalgia has always struggled to be taken seriously. The vague mixture of
      aches, pains, stiffness and fatigue with no clear clinical or investigational
      findings has led many to doubt its very existence. Evidence is accumulating,
      however, of demonstrable abnormalities of pain processing and psychosocial
      factors in fibromyalgia subjects. These may 'prove' its existence, but do they
      suggest it is rheumatological?

PMID- 22408216
TI  - Managing acute medical admissions: the plight of the medical boarder.
AB  - In an ideal system, patients admitted acutely to hospital should have their care
      provided in an area with the most appropriate ward-based medical, nursing and
      allied professional staff profile. Frequently this does not happen due to the
      physical structure and organisation of our hospitals in Scotland. Acute medical
      admissions may be fitted in to the end of many different speciality ward areas
      while still under the care of a single internal medicine team - as 'medical
      boarders'. A survey of local medical and nursing staff revealed that a majority
      would not wish their relatives to be cared for in this way. It remains important
      to provide speciality beds for those patients who require them, but it is also
      necessary to develop a system that enables more patients to receive optimal care
      in the correct environment. In this article, we describe the issue, the problems
      created and some possible solutions.

PMID- 22408217
TI  - The importance of informed consent in patients with wet age-related macular
      degeneration considering intravitreal anti-vascular endothelial growth factor
      treatments.
AB  - Retinal pigment epithelial (RPE) tears are now a documented potential
      complication following the intravitreal injection of anti-vascular endothelial
      growth factor (VEGF) treatments for neovascular age-related macular degeneration.
      Patients are often not well consented regarding this risk and thus we
      retrospectively analyzed the data from all of our patients undergoing this
      treatment over a six month period. Our findings highlighted the fact that the
      three patients (out of thirty) who had developed this RPE tear complication were
      initially all diagnosed with a pigment epithelial detachment (which is a type of
      macular degeneration in question). Therefore, we have adjusted our informed
      consent procedure such that all patients with "wet" macular degeneration and
      especially those with pigment epithelial detachments are now fully consented
      regarding the risks of the intravitreal treatment, which could potentially damage
      their vision further.

PMID- 22408219
TI  - Alcohol and drug misuse, risk of re-admission to a general hospital and
      psychiatric contact.
AB  - Patients with physical problems related to the use of alcohol or drugs often
      present to general hospitals in an unplanned, emergency fashion. In 2005, the
      Kerr report concluded that fundamental changes were needed in our approach,
      shifting the emphasis from a reactive to a more proactive, prevention-based model
      in the treatment of acute medical conditions. We studied patients who had at
      least one alcohol- or drug-related emergency admission, whose most recent
      admission was to Aberdeen Royal Infirmary and who, using the Scottish Patients at
      Risk of Re-admission and Admission (SPARRA) All Ages Tool, were thought to be at
      high risk of further emergency admission. We examined data sets derived from the
      National Health Service National Services Scotland Information Services Division,
      a Liaison Psychiatry database, data from the local psychiatric Patient
      Information Management System and data collected by the hospital alcohol liaison
      nurse to examine this group of patients further and consider the scope for any
      future intervention. Patients who have an alcohol- or drug-related emergency
      admission to the general hospital are at increased risk of re-admission. A
      substantial proportion of these patients has come into contact with the
      psychiatric services, often attracting a substance misuse and/or personality
      disorder diagnosis. A significant proportion also presents in the context of self
      harm. In conclusion, this group of frequent hospital attenders may be difficult
      to engage but may benefit from more proactive intervention, a more joined-up
      management approach and the development of an enhanced general hospital alcohol
      liaison service.

PMID- 22408220
TI  - Pyogenic ventriculitis following enteral bacterial translocation in a patient
      with small bowel obstruction.
AB  - The authors present a rare case of ventriculitis secondary to cerebro spinal
      fluid (CSF) colonization with Escherichia coli species in a 65-year-old woman.
      Passage of bacterial organisms from the lumen of the gastrointestinal tract to
      the bloodstream or lymphatic tissue is known as translocation. Once in the
      bloodstream, particular bacteria are able to cross the blood-brain barrier and
      migrate to CSF. Elective abdominal surgery, intestinal obstruction, colorectal
      cancer, ischaemic reperfusion injury and pancreatitis have all increased the risk
      of this phenomenon. This account highlights particular events in presentation and
      management of such a case, followed by a brief literature review.

PMID- 22408221
TI  - Perianal actinomycosis: a case study of this rare infection associated with
      nicorandil usage.
AB  - Perianal actinomycosis infection is a very rare occurrence and is challenging to
      diagnose. Nicorandil is a potassium channel agonist, which is used in the
      treatment of ischaemic heart disease. Its usage is associated with perianal
      ulceration and delayed surgical wound healing. We report a case of actinomycosis
      complicating a chronic perianal ulcer, which was associated with long-term
      nicorandil usage. It raised the suspicion of malignancy and required over six
      months of antimicrobial treatment to achieve satisfactory healing. Perianal
      actinomycosis results in chronic infection which spreads across tissue planes and
      can resemble an ulcerated malignancy. Nicorandil usage can result in perianal
      ulceration and produces conditions which are conducive to actinomycosis
      infection. In such cases, nicorandil therapy should be discontinued, if possible,
      and long-term systemic antibiotics form the mainstay of treatment.

PMID- 22408222
TI  - Audio-induced psychogenic non-epileptic seizures.
AB  - A 45-year-old woman presented with vague attacks, which consisted of headaches,
      confusion and sleepiness. An electroencephalograph was normal, but subsequent
      scans revealed the presence of a right-sided convexity meningioma. This was
      excised and complications led to the removal of an infected bone flap in a
      separate procedure the following year. Various types of 'seizures' resulted from
      the operation. These were described to involve both tonic-clonic and absence
      seizures. This continued for 18 years, unaffected by medication, until a
      specialist diagnosed pseudo-epilepsy, by fortune of a hospital fire alarm. The
      patient began a psychological intervention programme including cognitive
      behavioural therapy, which has significantly reduced episodes. In conclusion,
      psychogenic non-epileptic seizures may develop after intracranial neurosurgery
      undertaken for indications other than the control of refractory epileptic
      seizures. A diagnosis of psychogenic non-epileptic seizures should be considered
      in patients who develop refractory seizures after neurosurgery and managed
      appropriately.

PMID- 22408223
TI  - Primary necrotizing fasciitis of the breast: a case report and review of the
      literature.
AB  - Primary necrotizing fasciitis of the breast is extremely rare. We describe a case
      of a 51-year-old diabetic smoker who presented with primary necrotizing fasciitis
      of the breast, with signs of severe systemic sepsis. She required intravenous
      antibiotics, radical emergency surgery, intensive care treatment and inotropic
      support. After daily wound inspections and changes of dressings, the wound was
      amenable to delayed primary closure on day 6. We describe this case in detail and
      review the literature on this extremely rare, but potentially fatal, infection.

PMID- 22408224
TI  - Smouldering systemic mastocytosis presenting with cryptic life-threatening
      crises: case report and literature review.
AB  - Systemic mastocytosis (SM) is a rare, clonal disorder of the mast cell (MC) and
      its precursor cells. It is characterized by proliferation and accumulation of MCs
      within various organs, most commonly the skin. The clinical course is variable
      with indolent or smouldering and aggressive forms being described. We report the
      case of a middle-aged male patient with smouldering SM presenting with atypical
      recurrent life-threatening crises. The patient reported a 19-year history of
      chronic symptoms. The patient had four inpatient stays due to atypical life
      threatening crises, during which he has shown end organ damage (cardiac and
      renal). With each crisis the patient reported acute symptoms. The management of
      each of these episodes was complex and made more challenging by the patient's
      longstanding history of hypertension and ischaemic heart disease. In short, SM
      can present with unexplained life-threatening crises which can be confused for an
      infectious disease being acute in nature.

PMID- 22408225
TI  - Electrical phenotypes of calcium transport mutant strains of a filamentous
      fungus, Neurospora crassa.
AB  - We characterized the electrical phenotypes of mutants with mutations in genes
      encoding calcium transporters-a mechanosensitive channel homolog (MscS), a
      Ca(2+)/H(+) exchange protein (cax), and Ca(2+)-ATPases (nca-1, nca-2, nca-3)-as
      well as those of double mutants (the nca-2 cax, nca-2 nca-3, and nca-3 cax
      mutants). The electrical characterization used dual impalements to obtain cable
      corrected current-voltage measurements. Only two types of mutants (the MscS
      mutant; the nca-2 mutant and nca-2-containing double mutants) exhibited lower
      resting potentials. For the nca-2 mutant, on the basis of unchanged conductance
      and cyanide-induced depolarization of the potential, the cause is attenuated H(+)
      ATPase activity. The growth of the nca-2 mutant-containing strains was inhibited
      by elevated extracellular Ca(2+) levels, indicative of lesions in Ca(2+)
      homeostasis. However, the net Ca(2+) effluxes of the nca-2 mutant, measured
      noninvasively with a self-referencing Ca(2+)-selective microelectrode, were
      similar to those of the wild type. All of the mutants exhibited osmosensitivity
      similar to that of the wild type (the turgor of the nca-2 mutant was also similar
      to that of the wild type), suggesting that Ca(2+) signaling does not play a role
      in osmoregulation. The hyphal tip morphology and tip-localized mitochondria of
      the nca-2 mutant were similar to those of the wild type, even when the external
      [Ca(2+)] was elevated. Thus, although Ca(2+) homeostasis is perturbed in the nca
      2 mutant (B. J. Bowman et al., Eukaryot. Cell 10:654-661, 2011), the phenotype
      does not extend to tip growth or to osmoregulation but is revealed by lower H(+)
      ATPase activity.

PMID- 22408226
TI  - The Arthroderma benhamiae hydrophobin HypA mediates hydrophobicity and influences
      recognition by human immune effector cells.
AB  - Dermatophytes are the most common cause of superficial mycoses in humans and
      animals. They can coexist with their hosts for many years without causing
      significant symptoms but also cause highly inflammatory diseases. To identify
      mechanisms involved in the modulation of the host response during infection
      caused by the zoophilic dermatophyte Arthroderma benhamiae, cell wall-associated
      surface proteins were studied. By two-dimensional gel electrophoresis, we found
      that a hydrophobin protein designated HypA was the dominant cell surface protein.
      HypA was also detected in the supernatant during the growth and conidiation of
      the fungus. The A. benhamiae genome harbors only a single hydrophobin gene,
      designated hypA. A hypA deletion mutant was generated, as was a complemented hypA
      mutant strain (hypA(C)). In contrast to the wild type and the complemented
      strain, the hypA deletion mutant exhibited "easily wettable" mycelia and conidia,
      indicating the loss of surface hydrophobicity of both morphotypes. Compared with
      the wild type, the hypA deletion mutant triggered an increased activation of
      human neutrophil granulocytes and dendritic cells, characterized by an increased
      release of the immune mediators interleukin-6 (IL-6), IL-8, IL-10, and tumor
      necrosis factor alpha (TNF-alpha). For the first time, we observed the formation
      of neutrophil extracellular traps against dermatophytes, whose level of formation
      was increased by the DeltahypA mutant compared with the wild type. Furthermore,
      conidia of the DeltahypA strain were killed more effectively by neutrophils. Our
      data suggest that the recognition of A. benhamiae by the cellular immune defense
      system is notably influenced by the presence of the surface rodlet layer formed
      by the hydrophobin HypA.

PMID- 22408227
TI  - Motor protein Myo5p is required to maintain the regulatory circuit controlling
      WOR1 expression in Candida albicans.
AB  - The Candida albicans MYO5 gene encodes myosin I, a protein required for the
      formation of germ tubes and true hyphae. Because the polarized growth of opaque
      phase cells in response to pheromone results in mating projections that can
      resemble germ tubes, we examined the role of Myo5p in this process. We localized
      green fluorescent protein (GFP)-tagged Myo5p in opaque-phase cells of C. albicans
      during both bud and shmoo formation. In vegetatively growing opaque cells, Myo5p
      is found at sites of bud emergence and bud growth, while in pheromone-stimulated
      cells, Myo5p localizes at the growing tips of shmoos. Intriguingly, cells
      homozygous for MTLa in which the MYO5 gene was deleted failed to switch
      efficiently from the white phase to the opaque phase, although ectopic expression
      of WOR1 from the MET3 promoter can convert myo5 mutants into mating-competent
      opaque cells. However, when WOR1 expression was shut off, the myo5-defective
      cells rapidly lost both their opaque phenotype and mating competence, suggesting
      that Myo5p is involved in the maintenance of the opaque state. When MYO5 is
      expressed conditionally in opaque cells, the opaque phenotype, as well as the
      mating ability of the cells, becomes unstable under repressive conditions, and
      quantitative real-time PCR demonstrated that the shutoff of MYO5 expression
      correlates with a dramatic reduction in WOR1 expression. It appears that while
      myosin I is not directly required for mating in C. albicans, it is involved in
      WOR1 expression and the white-opaque transition and thus is indirectly implicated
      in mating.

PMID- 22408228
TI  - Histone H3 Variants in Trichomonas vaginalis.
AB  - The parabasalid protist Trichomonas vaginalis is a widespread parasite that
      affects humans, frequently causing vaginitis in infected women. Trichomonad
      mitosis is marked by the persistence of the nuclear membrane and the presence of
      an asymmetric extranuclear spindle with no obvious direct connection to the
      chromosomes. No centromeric markers have been described in T. vaginalis, which
      has prevented a detailed analysis of mitotic events in this organism. In other
      eukaryotes, nucleosomes of centromeric chromatin contain the histone H3 variant
      CenH3. The principal aim of this work was to identify a CenH3 homolog in T.
      vaginalis. We performed a screen of the T. vaginalis genome to retrieve sequences
      of canonical and variant H3 histones. Three variant histone H3 proteins were
      identified, and the subcellular localization of their epitope-tagged variants was
      determined. The localization of the variant TVAG_185390 could not be
      distinguished from that of the canonical H3 histone. The sequence of the variant
      TVAG_087830 closely resembled that of histone H3. The tagged protein colocalized
      with sites of active transcription, indicating that the variant TVAG_087830
      represented H3.3 in T. vaginalis. The third H3 variant (TVAG_224460) was
      localized to 6 or 12 distinct spots at the periphery of the nucleus,
      corresponding to the number of chromosomes in G(1) phase and G(2) phase,
      respectively. We propose that this variant represents the centromeric marker
      CenH3 and thus can be employed as a tool to study mitosis in T. vaginalis.
      Furthermore, we suggest that the peripheral distribution of CenH3 within the
      nucleus results from the association of centromeres with the nuclear envelope
      throughout the cell cycle.

PMID- 22408230
TI  - Complete genome sequence of porcine reproductive and respiratory syndrome virus
      isolated from piglet stool samples.
AB  - WUH4 is a highly pathogenic North American porcine reproductive and respiratory
      syndrome virus (PRRSV). Unlike previous PRRSV isolates, which were mainly
      recovered from sera or tissues, WUH4 was isolated from a piglet stool sample.
      Here we announce its complete genome sequence.

PMID- 22408231
TI  - Increased risk of uveitis in coeliac disease: a nationwide cohort study.
AB  - BACKGROUND: Case reports suggest a potential association between coeliac disease
      (CD) and uveitis, but larger well-controlled studies are lacking. The aim of this
      study was therefore to examine the risk of uveitis in patients with biopsy
      verified CD. METHODS: Small intestinal biopsy reports performed between July 1969
      and February 2008 were collected from all (n=28) pathology departments in Sweden.
      From these reports, 29,044 patients with CD (equals villous atrophy, Marsh 3)
      were identified. Uveitis was defined according to relevant International
      Classification of Disease codes in the Swedish National Patient Register. Cox
      regression was used to estimate HR for uveitis in individuals with CD compared
      with those in reference individuals matched for age, sex, county and calendar
      year. RESULTS: During follow-up, 148 patients with CD developed uveitis (expected
      count 112), corresponding to a HR of 1.32 (95% CI 1.10 to 1.58). The absolute
      risk of uveitis was 50/100,000 person-years in CD. The risk estimate did not
      change more than marginally when adjusted for type 1 diabetes, rheumatoid
      arthritis and autoimmune thyroid disease (HR 1.30; 95% CI 1.08 to 1.56). The risk
      of uveitis remained significantly increased even 5 years after CD diagnosis (HR
      1.31; 95% CI 1.04 to 1.64). CONCLUSION: A moderately increased risk of uveitis
      was found in patients with biopsy-verified CD. CD might be considered in patients
      with uveitis of unknown aetiology.

PMID- 22408232
TI  - The impact of bilateral or unilateral cataract surgery on visual functioning:
      when does second eye cataract surgery benefit patients?
AB  - AIM: To examine the impact of bilateral or unilateral cataract surgery on visual
      functioning. METHODS: The Singapore Malay Eye Study is a population-based study
      of 3280 Singapore Malay patients aged 40-80 years, of which 3225 had data
      available for inclusion. Cataracts were graded from digital lens photographs
      according to the Wisconsin scale. Study subjects were categorised as having:
      bilateral cataract surgery performed; unilateral cataract surgery performed with
      minimal cataract in the fellow eye; unilateral cataract surgery performed with
      significant cataract in the fellow eye; and bilateral cataract. Visual
      functioning was assessed using the modified VF-9 scale culturally adapted for
      Singaporean individuals, validated by Rasch analysis. The overall Rasch-modified
      vision-specific functioning score was compared across the four groups after
      adjusting for confounders such as age, gender, ocular and systemic comorbidities.
      RESULTS: Persons with bilateral cataract had poorer visual functioning than those
      who had bilateral cataract surgery (mean visual functioning scores 3.38 vs 3.11,
      respectively, p=0.029). When compared with bilateral surgery, visual functioning
      improvements among patients with unilateral cataract surgery depended on the
      status of the fellow eye, with improvements only seen if the fellow eye had
      significant cataract (mean visual functioning scores 2.81 vs 3.25, p=0.019) or
      poor visual acuity (mean visual functioning scores 2.78 vs 3.25, p=0.018) after
      adjusting for confounders. CONCLUSIONS: Bilateral cataract surgery was associated
      with greater visual functioning over unilateral cataract surgery when the fellow
      eye had a significant cataract or poor presenting visual acuity, supporting the
      current practice of second eye surgery depending on the fellow eye's cataract
      status and visual acuity.

PMID- 22408233
TI  - Comment on: the role of the optical coherence tomography in identifying shape and
      size of idiopathic epiretinal membranes.

PMID- 22408234
TI  - Frequency and associated factors of structural progression of open-angle glaucoma
      in the Beijing Eye Study.
AB  - BACKGROUND: To examine factors associated with progression of open-angle glaucoma
      in a population-based setting. METHODS: The population-based Beijing Eye Study,
      which included 4439 subjects with an age of 40+ years in the year 2001, was
      repeated in 2006. Optic disc photographs of the baseline examination versus
      follow-up examination were compared. RESULTS: Out of 111 open-angle glaucoma
      patients examined in 2001, 77 (69%) subjects participated in the follow-up
      examination and 16 (21%) eyes showed glaucoma progression. Glaucoma progression
      was associated with smaller rim area (p=0.001), larger beta zone (p=0.037),
      higher frequency of beta zone increase during follow-up (p=0.01), higher
      prevalence of disc haemorrhages (p=0.01) and higher single intraocular pressure
      (p=0.04). In multiple regression analysis, only smaller rim area remained
      significantly associated with glaucoma progression. Glaucoma progression was not
      associated with optic disc size (p=0.70), mean blood pressure (p=0.43), ocular
      perfusion pressure (p=0.96), retinal vessel diameter and retinal microvascular
      abnormalities (all p>0.10), prevalence of diabetes mellitus (p=0.75) and arterial
      hypertension (p=0.26), prevalence of dyslipidaemia (p=0.28), refractive error
      (p=0.69), and central corneal thickness (p=0.97). CONCLUSIONS: In a population
      based setting in adult Chinese, factors showing an association with open-angle
      glaucoma progression were an advanced stage of the disease (ie, small rim),
      presence of disc haemorrhages, larger area of beta zone and higher frequency of
      beta zone increase, and higher intraocular pressure. Glaucoma progression was not
      significantly associated with optic disc size, central corneal thickness, retinal
      vessel diameter and retinal microvascular abnormalities, and systemic diseases
      such as diabetes mellitus and arterial hypertension.

PMID- 22408235
TI  - Clinical outcome of the artificial iris diaphragm in silicone oil surgery.
AB  - BACKGROUND: Some eyes require long-term silicone oil tamponade. Problems arise in
      aphakic eyes with iris defects or hypotony, because an inferior iridectomy can
      not prevent silicone oil from entering the anterior chamber causing keratopathy
      and glaucoma. The artificial iris diaphragm was developed to prevent these
      complications. METHODS: In this retrospective case series, 94 consecutive aphakic
      eyes of 94 patients received an artificial iris diaphragm and a silicone oil
      tamponade. All eyes had hypotony or iris defects. The primary outcome measure was
      the retention of silicone oil behind the iris diaphragm. Secondary outcome
      measures included visual acuity, intraocular pressure and surgical revisions.
      RESULTS: The mean follow-up time was 586 days. No silicone oil in the anterior
      chamber at the last follow-up visit was found in 58 cases (61.7%). The Kaplan
      Meier survival analysis returned a mean survival time for a functional diaphragm
      of 1227 days. Keratopathy improved in 55.3% at least temporarily, and vision
      improved or remained stable in 38.2% until last follow-up. The diaphragm was more
      successful when the underlying disease was trauma or congenital malformation.
      CONCLUSIONS: The artificial iris diaphragm often retained silicone oil from the
      anterior chamber in severely damaged eyes. It can be useful to prevent phthisis
      and preserve vision.

PMID- 22408236
TI  - Reliability and validity of conjunctival ultraviolet autofluorescence
      measurement.
AB  - BACKGROUND: Conjunctival ultraviolet autofluorescence (UVAF) photography was
      developed to detect and characterise pre-clinical sunlight-induced UV damage. The
      reliability of this measurement and its relationship to outdoor activity are
      currently unknown. METHODS: 599 people aged 16-85 years in the cross-sectional
      Norfolk Island Eye Study were included in the validation study. 196 UVAF
      individual photographs (49 people) and 60 UVAF photographs (15 people) of Norfolk
      Island Eye Study participants were used for intra- and inter-observer reliability
      assessment, respectively. Conjunctival UVAF was measured using UV photography.
      UVAF area was calculated using computerised methods by one grader on two
      occasions (intra-observer analysis) or two graders (inter-observer analysis).
      Outdoor activity category, during summer and winter separately, was determined
      with a UV questionnaire. Total UVAF equalled the area measured in four
      conjunctival areas (nasal/temporal conjunctiva of right and left eyes). RESULTS:
      Intra-observer (rho_c=0.988, 95% CI 0.967 to 0.996, p<0.001), and inter-observer
      concordance correlation coefficients (rho_c=0.924, 95% CI 0.870 to 0.956,
      p<0.001) of total UVAF exceeded 0.900. When grouped according to 10 mm(2) total
      UVAF increments, intra- and inter-observer reliability was very good (kappa=0.81)
      and good (kappa=0.71), respectively. Increasing time outdoors was strongly with
      increasing total UVAF in summer and winter (p(trend) <0.001). CONCLUSION: Intra-
      and inter-observer reliability of conjunctival UVAF is high. In this population,
      UVAF correlates strongly with the authors' survey-based assessment of time spent
      outdoors.

PMID- 22408237
TI  - Same-different categorization in rats.
AB  - Same-different categorization is a fundamental feat of human cognition. Although
      birds and nonhuman primates readily learn same-different discriminations and
      successfully transfer them to novel stimuli, no such demonstration exists for
      rats. Using a spatial discrimination learning task, we show that rats can both
      learn to discriminate arrays of visual stimuli containing all same from all
      different items and transfer this discrimination to arrays composed of novel
      visual items. These results are consistent with rats' engaging in same-different
      categorization. As such, they pave the way for investigations into the
      perceptual, cognitive, and neurobiological substrates of abstract categorization
      behavior.

PMID- 22408238
TI  - Turning residual human biological materials into research collections: playing
      with consent.
AB  - This article focuses on three scenarios in which residual biological materials
      are turned into research collections during the procedure of procuring these
      materials for diagnostic, therapeutic or other non-research purposes. These three
      scenarios differ from each other primarily because they employ different models
      of consent: (a) precautionary consent, which may be secured during the collecting
      procedure; (b) the presumed consent model, which may be applied during the
      collection of materials; and (c) consent for research use of identifiable human
      biological materials, which may be skipped entirely. These scenarios offer
      additional sources of biological samples for research purposes and at the same
      time seem to offer even more flexibility in terms of stringency of consent as
      compared with the more traditional models of broad consent in prospective
      research collections and the waiver of consent in retrospective research. Our
      discussion leads us to think that precautionary consent is preferable to presumed
      consent and no consent when handling issues of consent in the use of residual
      human biological materials for research. However, such precautionary consent
      should not be construed as blanket, unrestricted consent for any future use.

PMID- 22408239
TI  - Draft genome of halomonas species strain GFAJ-1 (ATCC BAA-2256).
AB  - Halomonas strain GFAJ-1 was reported in Science magazine to be a remarkable
      microbe for which there was "arsenate in macromolecules that normally contain
      phosphate, most notably nucleic acids." The draft genome of the bacterium was
      determined (NCBI accession numbers AHBC01000001 through AHBC01000103). It appears
      to be a typical gamma proteobacterium.

PMID- 22408240
TI  - Genome sequence of a serotype b non-JP2 aggregatibacter actinomycetemcomitans
      strain, ANH9381, from a periodontally healthy individual.
AB  - Gram-negative Aggregatibacter actinomycetemcomitans can be distinguished (based
      on the promoter structure of the leukotoxin operon) into JP2 and non-JP2
      genotypes, with the former found to be more pathogenic than the latter. Here we
      report the first complete genome sequence of a serotype b non-JP2 strain of A.
      actinomycetemcomitans.

PMID- 22408241
TI  - Complete genome sequence of the dairy isolate Streptococcus macedonicus ACA-DC
      198.
AB  - The species Streptococcus macedonicus is associated with the food environment,
      especially with fermented dairy products. Here we present the complete 2.1-Mb
      genome sequence of strain ACA-DC 198, which was isolated from naturally fermented
      Greek kasseri cheese.

PMID- 22408242
TI  - Whole-genome sequence of Wolbachia strain wAlbB, an endosymbiont of tiger
      mosquito vector Aedes albopictus.
AB  - Although bacteria of the genus Wolbachia induced significant extended phenotypes
      to infected hosts, most molecular mechanisms involved are still unknown. To gain
      insight into the bacterial genetic determinants, we sequenced the whole genome of
      Wolbachia wAlbB strain, a commensal obligate intracellular of the tiger mosquito
      Aedes albopictus.

PMID- 22408243
TI  - Complete genome sequence of Klebsiella pneumoniae subsp. pneumoniae HS11286, a
      multidrug-resistant strain isolated from human sputum.
AB  - Klebsiella pneumoniae is an important pathogen commonly associated with
      opportunistic infections. Here we report the genome sequence of a strain,
      HS11286, isolated from human sputum in 2011 in Shanghai, China. It contains one
      chromosome (5.3 Mb), three multidrug resistance plasmids (~110 kb), including a
      carbapenemase producer, and three small plasmids (~3 kb).

PMID- 22408244
TI  - Draft genome sequence of Sphingomonas echinoides ATCC 14820.
AB  - Sphingomonas is a Gram-negative, yellow-pigmented, chemoheterotrophic, strictly
      aerobic bacterium. The bacterium is known to be metabolically versatile and can
      utilize a wide range of natural compounds as well as some types of environmental
      contaminants, such as creosote, polychlorinated biphenyls, etc. Here, we report
      the draft genome sequence of Sphingomonas echinoides ATCC 14820, which will
      provide additional information to enhance our understanding of metabolic
      versatility of Sphingomonas.

PMID- 22408245
TI  - Genome sequence of Pseudomonas sp. strain PAMC 25886, isolated from alpine
      glacial cryoconite.
AB  - Pseudomonas spp. have shown characteristics of efficiently metabolizing
      environmental pollutants and also producing exopolysaccharides known as biofilms.
      Here we present the draft genome sequence of Pseudomonas sp. strain PAMC 25886,
      which was isolated from glacier cryoconite in the Alps mountain permafrost region
      and which may provide further insight into biodegradative and/or biofilm
      producing mechanisms in a cold environment.

PMID- 22408246
TI  - The complete genome of Bacillus amyloliquefaciens subsp. plantarum CAU B946
      contains a gene cluster for nonribosomal synthesis of iturin A.
AB  - The genome of the rhizobacterium Bacillus amyloliquefaciens subsp. plantarum CAU
      B946 was 4.02 Mb in size and harbored 3,823 genes (coding sequences [CDS]). Nine
      giant gene clusters were dedicated to nonribosomal synthesis of antimicrobial
      compounds. Remarkably, strain CAU B946 possessed a gene cluster involved in
      synthesis of iturin A.

PMID- 22408247
TI  - Draft genome sequence of Streptomyces acidiscabies 84-104, an emergent plant
      pathogen.
AB  - A draft genome sequence of the plant pathogen Streptomyces acidiscabies 84-104,
      an emergent plant pathogen, is presented here. The genome is among the largest of
      streptomycetes, at more than 11 Mb, and encodes a 100-kb pathogenicity island
      (PAI) shared with other plant-pathogenic streptomycetes. The presence of this
      conserved PAI, and the remnants of a conserved integrase/recombinase at its 3'
      end, supports the hypothesis that S. acidiscabies emerged as a plant pathogen as
      a result of this acquisition.

PMID- 22408248
TI  - Genome sequence of Mycoplasma hyorhinis strain GDL-1.
AB  - Mycoplasma hyorhinis impacts swine health and production in many countries,
      either as a primary pathogen or as a component of a polymicrobial infection.
      Isolates of this species are also common contaminants of tissue culture lines.
      The genome sequence of the cell culture isolate M. hyorhinis GDL-1 is presented
      herein.

PMID- 22408249
TI  - Proteasome inhibition can impair caspase-8 activation upon submaximal stimulation
      of apoptotic tumor necrosis factor-related apoptosis inducing ligand (TRAIL)
      signaling.
AB  - Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can induce
      extrinsic apoptosis, resulting in caspase-8 activation, but may also initiate
      transcription-dependent prosurvival signaling. Proteasome inhibitors were
      suggested to promote TRAIL signal transduction through the death-inducing
      signaling complex (DISC) by modulating the relative abundance of core DISC
      components, thereby enhancing caspase-8 activation and apoptosis. To test this
      hypothesis, we quantified the changes in DISC protein levels as an early
      consequence of proteasome inhibition in HeLa cervical cancer cells and, based on
      these data, mathematically modeled the proapoptotic TRAIL signaling toward
      caspase-8 activation. Modeling results surprisingly suggested that caspase-8
      activation might be delayed in presence of proteasome inhibitors, in particular
      at submaximal TRAIL doses. Subsequent FRET-based single cell time-lapse imaging
      at conditions where transcription dependent prosurvival signaling was blocked
      confirmed this hypothesis: caspase-8 activity was delayed by hours in the
      presence of proteasome inhibitors epoxomicin or bortezomib. Corresponding delays
      were detected for effector caspase processing and cell death. Contrary to current
      models, we therefore provide evidence that synergies between TRAIL and proteasome
      inhibitors do not result from changes in the levels of core DISC signaling
      proteins.

PMID- 22408250
TI  - Extracellular finger domain modulates the response of the epithelial sodium
      channel to shear stress.
AB  - The epithelial sodium channel (ENaC) is regulated by multiple extracellular
      stimuli, including shear stress. Previous studies suggest that the extracellular
      finger domains of ENaC alpha and gamma subunits contain allosteric regulatory
      modules. However, the role of the finger domain in the shear stress response is
      unknown. We examined whether mutations of specific residues in the finger domain
      of the alpha subunit altered the response of channels to shear stress. We
      observed that Trp substitutions at multiple sites within the tract alphaLys-250
      alphaLeu-290 altered the magnitude or kinetics of channel activation by shear
      stress. Consistent with these findings, deletion of two predicted peripheral beta
      strands (alphaIle-251-alphaTyr-268) led to slower channel activation by shear
      stress, suggesting that these structures participate in the shear stress
      response. The effects of mutations on the shear stress response did not correlate
      with their effects on allosteric Na(+) inhibition (i.e. Na(+) self-inhibition),
      indicating a divergence within the finger domain regarding mechanisms by which
      the channel responds to these two external stimuli. This result contrasts with
      well correlated effects we previously observed at sites near the extracellular
      mouth of the pore, suggesting mechanistic convergence in proximity to the pore.
      Our results suggest that the finger domain has an important role in the
      modulation of channel activity in response to shear stress.

PMID- 22408251
TI  - Protein translocase of mitochondrial inner membrane in Trypanosoma brucei.
AB  - Translocases of mitochondrial inner membrane (TIMs) are multiprotein complexes.
      The only Tim component so far characterized in kinetoplastid parasites such as
      Trypanosoma brucei is Tim17 (TbTim17), which is essential for cell survival and
      mitochondrial protein import. Here, we report that TbTim17 is present in a
      protein complex of about 1,100 kDa, which is much larger than the TIM complexes
      found in fungi and mammals. Depletion of TbTim17 in T. brucei impairs the
      mitochondrial import of cytochrome oxidase subunit IV, an N-terminal signal
      containing protein. Pretreatment of isolated mitoplasts with the anti-TbTim17
      antibody inhibited import of cytochrome oxidase subunit IV, indicating a direct
      involvement of the TbTim17 in the import process. Purification of the TbTim17
      containing protein complex from the mitochondrial membrane of T. brucei by tandem
      affinity chromatography revealed that TbTim17 associates with seven unique as
      well as a few known T. brucei mitochondrial proteins. Depletion of three of these
      novel proteins, i.e. TbTim47, TbTim54, and TbTim62, significantly decreased
      mitochondrial protein import in vitro. In vivo targeting of a newly synthesized
      mitochondrial matrix protein, MRP2, was also inhibited due to depletion of
      TbTim17, TbTim54, and TbTim62. Co-precipitation analysis confirmed the
      interaction of TbTim54 and TbTim62 with TbTim17 in vivo. Overall, our data reveal
      that TbTim17, the single homolog of Tim17/22/23 family proteins, is present in a
      unique TIM complex consisting of novel proteins in T. brucei and is critical for
      mitochondrial protein import.

PMID- 22408252
TI  - Induction of autophagy by palmitic acid via protein kinase C-mediated signaling
      pathway independent of mTOR (mammalian target of rapamycin).
AB  - Lipotoxicity refers to the cytotoxic effects of excess fat accumulation in cells
      and has been implicated as one of the contributing factors to diseases like
      obesity, diabetes, and non-alcoholic fatty liver. In this study we sought to
      examine effects of palmitic acid (PA) and oleic acid, two of the common dietary
      fatty acids on the autophagic process. We found that PA, but not oleic acid, was
      able to cause an increase in autophagic flux, evidenced by LC3-II accumulation
      and formation of GFP-LC3 puncta. Notably, PA-induced autophagy was found to be
      independent of mTOR regulation. Next, in search of the mechanism mediating PA
      induced autophagy, we found increased levels of diacylglycerol species and
      protein kinase C (PKC) activation in PA-treated cells. More importantly,
      inhibition of classical PKC isoforms (PKC-alpha) was able to effectively suppress
      PA-induced autophagy. Finally, we showed that inhibition of autophagy sensitized
      the cells to PA-induced apoptosis, suggesting the pro-survival function of
      autophagy induced by PA. Taken together, results from this study reveal a novel
      mechanism underlying free fatty acid-mediated autophagy. Furthermore, the pro
      survival function of autophagy suggests modulation of autophagy as a potential
      therapeutic strategy in protection of cells against lipotoxicity and lipid
      related metabolic diseases.

PMID- 22408254
TI  - Reversible lysine acetylation regulates activity of human glycine N
      acyltransferase-like 2 (hGLYATL2): implications for production of glycine
      conjugated signaling molecules.
AB  - Lysine acetylation is a major post-translational modification of proteins and
      regulates many physiological processes such as metabolism, cell migration, aging,
      and inflammation. Proteomic studies have identified numerous lysine-acetylated
      proteins in human and mouse models (Kim, S. C., Sprung, R., Chen, Y., Xu, Y.,
      Ball, H., Pei, J., Cheng, T., Kho, Y., Xiao, H., Xiao, L., Grishin, N. V., White,
      M., Yang, X. J., and Zhao, Y. (2006) Mol. Cell 23, 607-618). One family of
      proteins identified in this study was the murine glycine N-acyltransferase
      (GLYAT) enzymes, which are acetylated on lysine 19. Lysine 19 is a conserved
      residue in human glycine N-acyltransferase-like 2 (hGLYATL2) and in several other
      species, showing that this residue may be important for enzyme function. Mutation
      of lysine 19 in recombinant hGLYATL2 to glutamine (K19Q) and arginine (K19R)
      resulted in a 50-80% lower production of N-oleoyl glycine and N
      arachidonoylglycine, indicating that lysine 19 is important for enzyme function.
      LC/MS/MS confirmed that Lys-19 is not acetylated in wild-type hGLYATL2,
      indicating that Lys-19 requires to be deacetylated for full activity. The
      hGLYATL2 enzyme conjugates medium- and long-chain saturated and unsaturated acyl
      CoA esters to glycine, resulting in the production of N-oleoyl glycine and also N
      arachidonoyl glycine. N-Oleoyl glycine and N-arachidonoyl glycine are
      structurally and functionally related to endocannabinoids and have been
      identified as signaling molecules that regulate functions like the perception of
      pain and body temperature and also have anti-inflammatory properties. In
      conclusion, acetylation of lysine(s) in hGLYATL2 regulates the enzyme activity,
      thus linking post-translational modification of proteins with the production of
      biological signaling molecules, the N-acyl glycines.

PMID- 22408253
TI  - Functional and structural analysis of the siderophore synthetase AsbB through
      reconstitution of the petrobactin biosynthetic pathway from Bacillus anthracis.
AB  - Petrobactin, a mixed catechol-carboxylate siderophore, is required for full
      virulence of Bacillus anthracis, the causative agent of anthrax. The asbABCDEF
      operon encodes the biosynthetic machinery for this secondary metabolite. Here, we
      show that the function of five gene products encoded by the asb operon is
      necessary and sufficient for conversion of endogenous precursors to petrobactin
      using an in vitro system. In this pathway, the siderophore synthetase AsbB
      catalyzes formation of amide bonds crucial for petrobactin assembly through use
      of biosynthetic intermediates, as opposed to primary metabolites, as carboxylate
      donors. In solving the crystal structure of the B. anthracis siderophore
      biosynthesis protein B (AsbB), we disclose a three-dimensional model of a
      nonribosomal peptide synthetase-independent siderophore (NIS) synthetase.
      Structural characteristics provide new insight into how this bifunctional
      condensing enzyme can bind and adenylate multiple citrate-containing substrates
      followed by incorporation of both natural and unnatural polyamine nucleophiles.
      This activity enables formation of multiple end-stage products leading to final
      assembly of petrobactin. Subsequent enzymatic assays with the nonribosomal
      peptide synthetase-like AsbC, AsbD, and AsbE polypeptides show that the
      alternative products of AsbB are further converted to petrobactin, verifying
      previously proposed convergent routes to formation of this siderophore. These
      studies identify potential therapeutic targets to halt deadly infections caused
      by B. anthracis and other pathogenic bacteria and suggest new avenues for the
      chemoenzymatic synthesis of novel compounds.

PMID- 22408255
TI  - Differential expression of sodium channel beta subunits in dorsal root ganglion
      sensory neurons.
AB  - The small-diameter (<25 MUm) and large-diameter (>30 MUm) sensory neurons of the
      dorsal root ganglion (DRG) express distinct combinations of tetrodotoxin
      sensitive and tetrodotoxin-resistant Na(+) channels that underlie the unique
      electrical properties of these neurons. In vivo, these Na(+) channels are formed
      as complexes of pore-forming alpha and auxiliary beta subunits. The goal of this
      study was to investigate the expression of beta subunits in DRG sensory neurons.
      Quantitative single-cell RT-PCR revealed that beta subunit mRNA is differentially
      expressed in small (beta(2) and beta(3)) and large (beta(1) and beta(2)) DRG
      neurons. This raises the possibility that beta subunit availability and Na(+)
      channel composition and functional regulation may differ in these subpopulations
      of sensory neurons. To further explore these possibilities, we quantitatively
      compared the mRNA expression of the beta subunit with that of Na(v)1.7, a TTX
      sensitive Na(+) channel widely expressed in both small and large DRG neurons.
      Na(v)1.7 and beta subunit mRNAs were significantly correlated in small (beta(2)
      and beta(3)) and large (beta(1) and beta(2)) DRG neurons, indicating that these
      subunits are coexpressed in the same populations. Co-immunoprecipitation and
      immunocytochemistry indicated that Na(v)1.7 formed stable complexes with the
      beta(1)-beta(3) subunits in vivo and that Na(v)1.7 and beta(3) co-localized
      within the plasma membranes of small DRG neurons. Heterologous expression studies
      showed that beta(3) induced a hyperpolarizing shift in Na(v)1.7 activation,
      whereas beta(1) produced a depolarizing shift in inactivation and faster
      recovery. The data indicate that beta(3) and beta(1) subunits are preferentially
      expressed in small and large DRG neurons, respectively, and that these auxiliary
      subunits differentially regulate the gating properties of Na(v)1.7 channels.

PMID- 22408256
TI  - Expression of ABO blood-group genes is dependent upon an erythroid cell-specific
      regulatory element that is deleted in persons with the B(m) phenotype.
AB  - The ABO blood group is of great importance in blood transfusion and organ
      transplantation. However, the mechanisms regulating human ABO gene expression
      remain obscure. On the basis of DNase I-hypersensitive sites in and upstream of
      ABO in K562 cells, in the present study, we prepared reporter plasmid constructs
      including these sites. Subsequent luciferase assays indicated a novel positive
      regulatory element in intron 1. This element was shown to enhance ABO promoter
      activity in an erythroid cell-specific manner. Electrophoretic mobility-shift
      assays demonstrated that it bound to the tissue-restricted transcription factor
      GATA-1. Mutation of the GATA motifs to abrogate binding of this factor reduced
      the regulatory activity of the element. Therefore, GATA-1 appears to be involved
      in the cell-specific activity of the element. Furthermore, we found that a
      partial deletion in intron 1 involving the element was associated with B(m)
      phenotypes. Therefore, it is plausible that deletion of the erythroid cell
      specific regulatory element could down-regulate transcription in the B(m) allele,
      leading to reduction of B-antigen expression in cells of erythroid lineage, but
      not in mucus-secreting cells. These results support the contention that the
      enhancer-like element in intron 1 of ABO has a significant function in erythroid
      cells.

PMID- 22408257
TI  - Reduced intensity conditioning is superior to nonmyeloablative conditioning for
      older chronic myelogenous leukemia patients undergoing hematopoietic cell
      transplant during the tyrosine kinase inhibitor era.
AB  - Tyrosine kinase inhibitors (TKIs) and reduced intensity conditioning
      (RIC)/nonmyeloablative (NMA) conditioning hematopoietic cell transplants (HCTs)
      have changed the therapeutic strategy for chronic myelogenous leukemia (CML)
      patients. We analyzed post-HCT outcomes of 306 CML patients reported to the
      Center for International Blood and Marrow Transplant Research aged 40 years and
      older undergoing RIC/NMA HCT from 2001 to 2007: 117 (38%) aged 40 to 49 years,
      119 (39%) 50 to 59 years, and 70 (23%) 60 years or older. The majority (74%) had
      treatment with imatinib before HCT. At HCT, most patients aged 40 to 49 years
      were in chronic phase (CP) 1 (74%), compared with 31% aged 60 years or older.
      Siblings were donors for 56% aged 40 to 49 years; older cohorts had more
      unrelated donors. The majority received peripheral blood grafts and RIC across
      all age groups. 3 year overall survival (54%, 52%, and 41%), day + 100 grade II
      IV acute GVHD (26%, 32%, and 32%), chronic GVHD (58%, 51%, and 43%), and 1-year
      treatment-related mortality (18%, 20%, and 13%) were similar across ages. The 3
      year relapse incidence (36%, 43%, and 66%) and disease-free survival (35%, 32%,
      and 16%) were inferior in the oldest cohort. Importantly, for CP1 patients,
      relapse and disease-free survival were similar across age cohorts. Allogeneic RIC
      HCT for older patients with CML can control relapse with acceptable toxicity and
      survival in TKI-exposed CML, especially if still in CP1.

PMID- 22408258
TI  - Stem cell heterogeneity: implications for aging and regenerative medicine.
AB  - For decades, hematopoietic stem cells (HSCs) were thought to be a homogeneous
      population of cells with flexible behavior. Now a new picture has emerged: The
      HSC compartment consists of several subpopulations of HSCs each with distinct,
      preprogrammed differentiation and proliferation behaviors. These programs are
      epigenetically fixed and are stably bequeathed to all daughter HSCs on self
      renewal. HSCs within each subset are remarkably similar in their self- renewal
      and differentiation behaviors, to the point where their life span can be
      predicted with mathematical certainty. Three subsets can be distinguished when
      HSCs are classified by their differentiation capacity: myeloid-biased, balanced,
      and lymphoid-biased HSCs. The relative number of the HSC subsets is
      developmentally regulated. Lymphoid-biased HSCs are found predominantly early in
      the life of an organism, whereas myeloid-biased HSCs accumulate in aged mice and
      humans. Thus, the discovery of distinct subpopulations of HSCs has led to a new
      understanding of HCS aging. This finding has implications for other aspects of
      HSC biology and applications in re-generative medicine. The possibility that
      other adult tissue stem cells show similar heterogeneity and mechanisms of aging
      is discussed.

PMID- 22408259
TI  - The FA pathway counteracts oxidative stress through selective protection of
      antioxidant defense gene promoters.
AB  - Oxidative stress has been implicated in the pathogenesis of many human diseases
      including Fanconi anemia (FA), a genetic disorder associated with BM failure and
      cancer. Here we show that major antioxidant defense genes are down-regulated in
      FA patients, and that gene down-regulation is selectively associated with
      increased oxidative DNA damage in the promoters of the antioxidant defense genes.
      Assessment of promoter activity and DNA damage repair kinetics shows that
      increased initial damage, rather than a reduced repair rate, contributes to the
      augmented oxidative DNA damage. Mechanistically, FA proteins act in concert with
      the chromatin-remodeling factor BRG1 to protect the promoters of antioxidant
      defense genes from oxidative damage. Specifically, BRG1 binds to the promoters of
      the antioxidant defense genes at steady state. On challenge with oxidative
      stress, FA proteins are recruited to promoter DNA, which correlates with
      significant increase in the binding of BRG1 within promoter regions. In addition,
      oxidative stress-induced FANCD2 ubiquitination is required for the formation of a
      FA-BRG1-promoter complex. Taken together, these data identify a role for the FA
      pathway in cellular antioxidant defense.

PMID- 22408260
TI  - Regulation of acute graft-versus-host disease by microRNA-155.
AB  - Acute graft-versus-host disease (aGVHD) remains a major complication of
      allogeneic hematopoietic stem cell transplant (alloHSCT), underscoring the need
      to further elucidate its mechanisms and develop novel treatments. Based on recent
      observations that microRNA-155 (miR-155) is up-regulated during T-cell
      activation, we hypothesized that miR-155 is involved in the modulation of aGVHD.
      Here we show that miR-155 expression was up-regulated in T cells from mice
      developing aGVHD after alloHSCT. Mice receiving miR-155-deficient donor
      lymphocytes had markedly reduced lethal aGVHD, whereas lethal aGVHD developed
      rapidly in mice recipients of miR-155 overexpressing T cells. Blocking miR-155
      expression using a synthetic anti-miR-155 after alloHSCT decreased aGVHD severity
      and prolonged survival in mice. Finally, miR-155 up-regulation was shown in
      specimens from patients with pathologic evidence of intestinal aGVHD. Altogether,
      our data indicate a role for miR-155 in the regulation of GVHD and point to miR
      155 as a novel target for therapeutic intervention in this disease.

PMID- 22408261
TI  - The pan-deacetylase inhibitor panobinostat induces cell death and synergizes with
      everolimus in Hodgkin lymphoma cell lines.
AB  - The pan-deacetylase inhibitor panobinostat (LBH589) recently has been shown to
      have significant clinical activity in patients with relapsed Hodgkin lymphoma,
      but its mechanism of action in Hodgkin lymphoma remains unknown. In this study,
      we demonstrate that panobinostat has potent antiproliferative activity against
      Hodgkin lymphoma-derived cell lines. At the molecular level, panobinostat
      activated the caspase pathway, inhibited STAT5 and STAT6 phosphorylation, and
      down-regulated hypoxia-inducible factor 1 alpha and its downstream targets,
      glucose transporter 1 (GLUT1) and vascular endothelial growth factor.
      Paradoxically, panobinostat inhibited LKB1 and AMP-activated protein kinase,
      leading to activation of mammalian target of rapamycin (mTOR) that promotes
      survival. Combining panobinostat with the mTOR inhibitor everolimus (RAD001)
      inhibited panobinostat-induced mTOR activation and enhanced panobinostat
      antiproliferative effects. Collectively, our data demonstrate that panobinostat
      is a potent deacetylase inhibitor against Hodgkin lymphoma-derived cell lines,
      and provide a mechanistic rationale for combining panobinostat with mTOR
      inhibitors for treating Hodgkin lymphoma patients. Furthermore, the effect of
      panobinostat on GLUT1 expression suggests that panobinostat may modulate the
      results of clinical diagnostic imaging tests that depend of functional GLUT1,
      such as fluorodeoxyglucose positron emission tomography.

PMID- 22408262
TI  - Efficacy of vorinostat in a murine model of polycythemia vera.
AB  - The discovery of the JAK2V617F mutation in most patients with Ph-negative
      myeloproliferative neoplasms has led to the development of JAK2 kinase
      inhibitors. However, JAK2 inhibitor therapy has shown limited efficacy and dose
      limiting hematopoietic toxicities in clinical trials. In the present study, we
      describe the effects of vorinostat, a small-molecule inhibitor of histone
      deacetylase, against cells expressing JAK2V617F and in an animal model of
      polycythemia vera (PV). We found that vorinostat markedly inhibited proliferation
      and induced apoptosis in cells expressing JAK2V617F. In addition, vorinostat
      significantly inhibited JAK2V617F-expressing mouse and human PV hematopoietic
      progenitors. Biochemical analyses revealed significant inhibition of
      phosphorylation of JAK2, Stat5, Stat3, Akt, and Erk1/2 in vorinostat-treated,
      JAK2V617F-expressing human erythroleukemia (HEL) cells. Expression of JAK2V617F
      and several other genes, including GATA1, KLF1, FOG1, SCL, C/EPBalpha, PU.1, and
      NF-E2, was significantly down-regulated, whereas the expression of SOCS1 and
      SOCS3 was up-regulated by vorinostat treatment. More importantly, we observed
      that vorinostat treatment normalized the peripheral blood counts and markedly
      reduced splenomegaly in Jak2V617F knock-in mice compared with placebo treatment.
      Vorinostat treatment also decreased the mutant allele burden in mice. Our results
      suggest that vorinostat may have therapeutic potential for the treatment of PV
      and other JAK2V617F-associated myeloproliferative neoplasms.

PMID- 22408264
TI  - Leukemia-initiating cells of patient-derived acute lymphoblastic leukemia
      xenografts are sensitive toward TRAIL.
AB  - Cancer stem cells represent the most important target cells for antitumor
      therapy. TRAIL (TNF-related apoptosis-inducing ligand) is a potential anticancer
      agent that induces apoptosis in a wide variety of tumor cells, but its ability to
      target cancer stem cells is currently unknown. Here we investigated whether TRAIL
      targets leukemia-initiating cells. Limiting dilution transplantation assays were
      performed on xenografts from pediatric patients with precursor B-cell acute
      lymphoblastic leukemia (pre-B ALL) in NSG mice. In vitro treatment of xenograft
      cells with TRAIL significantly reduced and delayed their engraftment and
      procrastinated animal death from leukemia. Systemic TRAIL treatment of mice
      injected with patient-derived pre-B ALL xenograft cells abrogated leukemia in 3
      of 5 mice in 1 sample. In conclusion, our data suggest that TRAIL targets
      leukemia-initiating cells derived from pre-B ALL xenografts in vitro and in vivo,
      and hence constitutes an attractive candidate drug for treatment of ALL.

PMID- 22408265
TI  - The medical management of problem gamblers.

PMID- 22408263
TI  - MYC+ diffuse large B-cell lymphoma is not salvaged by classical R-ICE or R-DHAP
      followed by BEAM plus autologous stem cell transplantation.
AB  - Approximately 5-10% of diffuse large B-cell lymphomas (DLBCL) harbor a 8q24/MYC
      rearrangement (MYC(+)). We determined the prognostic significance of MYC
      rearrangement in patients with relapsed/refractory DLBCL prospectively treated by
      R-ICE or R-DHAP followed by high-dose therapy and autologous stem cell
      transplantation. Twenty-eight (17%) of the 161 patients analyzed presented a
      MYC(+) rearrangement, targeted as either simple hit (25%) or complex hits (n=75%)
      including MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6. Results were statistically
      highly concordant in matched primary and relapsed biopsies (n = 45). Compared to
      the MYC(-) DLBCL patients, the MYC(+) DLBCL patients presented with a more
      elevated lactico-deshydrogenase level (P = .0006) and a more advanced age
      adjusted international prognostic index (P = .0039). The 4-year PFS and OS were
      significantly lower in the MYC(+) DLBCL patients than those in the MYC(-) DLBCL
      patients, with rates of 18% vs 42% (P = .0322), and of 29% vs 62% (P = .0113),
      respectively. Type of treatment, R-DHAP or R-ICE, had no impact on survivals,
      with 4-year PFS rates of 17% vs 19% and 4-year OS rates of 26% vs 31%. In
      conclusion, MYC rearrangement is an early event in DLBCL. MYC(+) DLBCL patients
      have a significant inferior prognosis than MYC(-) DLBCL patients. Their outcome
      was not influenced by the proposed salvage therapy.

PMID- 22408266
TI  - Discontinuation of antidepressants in people with dementia and neuropsychiatric
      symptoms (DESEP study): double blind, randomised, parallel group, placebo
      controlled trial.
AB  - OBJECTIVE: To determine the effect of discontinuing antidepressant treatment in
      people with dementia and neuropsychiatric symptoms. DESIGN: Double blind,
      randomised, parallel group, placebo controlled trial. SETTING: Norwegian nursing
      homes; residents recruited by 16 study centres in Norway from August 2008 to June
      2010. PARTICIPANTS: 128 patients with Alzheimer's disease, dementia or vascular
      dementia, and neuropsychiatric symptoms (but no depressive disorder), who had
      been prescribed escitalopram, citalopram, sertraline, or paroxetine for three
      months or more. We excluded patients with severe somatic disease or terminal
      illness, or who were unable to take tablets or capsules as prescribed.
      INTERVENTIONS: Antidepressant treatment was discontinued over one week in 63
      patients, and continued in 68 patients. We assessed patients at baseline, four,
      seven, 13, and 25 weeks. MAIN OUTCOME MEASURES: Primary outcomes were score
      differences between study groups in the Cornell scale of depression in dementia
      and the neuropsychiatric inventory (10 item version) after 25 weeks. Secondary
      outcomes were score differences in the clinical dementia rating scale, unified
      Parkinson's disease rating scale, quality of life-Alzheimer's disease scale,
      Lawton and Brody's physical self maintenance scale, and severe impairment
      battery. RESULTS: Using a linear multilevel model analysis, we found that the
      discontinued group had significantly higher scores on the Cornell scale after 25
      weeks than the continuation group (difference -2.89 (95% confidence interval 
      4.76 to -1.02); P=0.003). We saw a similar result in the mean total score for the
      neuropsychiatric inventory after 25 weeks, but this difference was non
      significant (-5.96 (-12.35 to 0.44); P=0.068). We confirmed these results by non
      response analysis (>30% worsening on the Cornell scale)--significantly more
      patients worsened in the discontinuation group than in the continuation group (32
      (54%) v 17 (29%); P=0.006). We found no significant differences between the
      groups for secondary outcomes. Forty seven (37%) patients withdrew from the study
      early. CONCLUSIONS: Discontinuation of antidepressant treatment in patients with
      dementia and neuropsychiatric symptoms leads to an increase in depressive
      symptoms, compared with those patients who continue with treatment. TRIAL
      REGISTRATION: ClinicalTrial.gov NCT00594269, EudraCT 2006-002790-43.

PMID- 22408267
TI  - Peers defeat government plans to abolish legal aid for clinical negligence cases.

PMID- 22408268
TI  - The effect of different linkers on target cell catabolism and
      pharmacokinetics/pharmacodynamics of trastuzumab maytansinoid conjugates.
AB  - Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate consisting of the
      anti-HER2 antibody trastuzumab linked via a nonreducible thioether linker to the
      maytansinoid antitubulin agent DM1. T-DM1 has shown favorable safety and efficacy
      in patients with HER2-positive metastatic breast cancer. In previous animal
      studies, T-DM1 exhibited better pharmacokinetics (PK) and slightly more efficacy
      than several disulfide-linked versions. The efficacy findings are unique, as
      other disulfide-linked antibody-drug conjugates (ADC) have shown greater efficacy
      than thioether-linked designs. To explore this further, the in vitro and in vivo
      activity, PK, and target cell activation of T-DM1 and the disulfide-linked T-SPP
      DM1 were examined. Both ADCs showed high in vitro potency, with T-DM1 displaying
      greater potency in two of four breast cancer cell lines. In vitro target cell
      processing of T-DM1 and T-SPP-DM1 produced lysine-N(epsilon)-MCC-DM1, and lysine
      N(epsilon)-SPP-DM1 and DM1, respectively; in vivo studies confirmed these
      results. The in vitro processing rates for the two conjugate to their respective
      catabolites were similar. In vivo, the potencies of the conjugates were similar,
      and T-SPP-DM1 had a faster plasma clearance than T-DM1. Slower T-DM1 clearance
      translated to higher overall tumor concentrations (conjugate plus catabolites),
      but unexpectedly, similar levels of tumor catabolite. These results indicate
      that, although the ADC linker can have clear impact on the PK and the chemical
      nature of the catabolites formed, both linkers seem to offer the same payload
      delivery to the tumor.

PMID- 22408269
TI  - Protective effects of antiretrovirals are confirmed in community setting.

PMID- 22408271
TI  - Anaesthesia and epilepsy.
AB  - Epilepsy is the most common serious neurological disorder, with a prevalence of
      0.5-1% of the population. While the traditional antiepileptic drugs (AEDs) still
      play a significant role in treatment of seizures, there has been an influx of
      newer agents over the last 20 yr, which are now in common usage. Anaesthetists
      are frequently faced with patients with epilepsy undergoing emergency or elective
      surgery and patients suffering seizures and status epilepticus in the intensive
      care unit (ICU). This review examines perioperative epilepsy management, the mode
      of action of AEDs and their interaction with anaesthetic agents, potential
      adverse effects of anaesthetic agents, and the acute management of seizures and
      refractory status epilepticus on the ICU. Relevant literature was identified by a
      Pubmed search of epilepsy and status epilepticus in conjunction with individual
      anaesthetic agents.

PMID- 22408270
TI  - Motor deficits correlate with resting state motor network connectivity in
      patients with brain tumours.
AB  - While a tumour in or abutting primary motor cortex leads to motor weakness, how
      tumours elsewhere in the frontal or parietal lobes affect functional connectivity
      in a weak patient is less clear. We hypothesized that diminished functional
      connectivity in a distributed network of motor centres would correlate with motor
      weakness in subjects with brain masses. Furthermore, we hypothesized that
      interhemispheric connections would be most vulnerable to subtle disruptions in
      functional connectivity. We used task-free functional magnetic resonance imaging
      connectivity to probe motor networks in control subjects and patients with brain
      tumours (n = 22). Using a control dataset, we developed a method for automated
      detection of key nodes in the motor network, including the primary motor cortex,
      supplementary motor area, premotor area and superior parietal lobule, based on
      the anatomic location of the hand-motor knob in the primary motor cortex. We then
      calculated functional connectivity between motor network nodes in control
      subjects, as well as patients with and without brain masses. We used this
      information to construct weighted, undirected graphs, which were then compared to
      variables of interest, including performance on a motor task, the grooved
      pegboard. Strong connectivity was observed within the identified motor networks
      between all nodes bilaterally, and especially between the primary motor cortex
      and supplementary motor area. Reduced connectivity was observed in subjects with
      motor weakness versus subjects with normal strength (P < 0.001). This difference
      was driven mostly by decreases in interhemispheric connectivity between the
      primary motor cortices (P < 0.05) and between the left primary motor cortex and
      the right premotor area (P < 0.05), as well as other premotor area connections.
      In the subjects without motor weakness, however, performance on the grooved
      pegboard did not relate to interhemispheric connectivity, but rather was
      inversely correlated with connectivity between the left premotor area and left
      supplementary motor area, for both the left and the right hands (P < 0.01).
      Finally, two subjects who experienced severe weakness following surgery for their
      brain tumours were followed longitudinally, and the subject who recovered showed
      reconstitution of her motor network at follow-up. The subject who was
      persistently weak did not reconstitute his motor network. Motor weakness in
      subjects with brain tumours that do not involve primary motor structures is
      associated with decreased connectivity within motor functional networks,
      particularly interhemispheric connections. Motor networks become weaker as the
      subjects become weaker, and may become strong again during motor recovery.

PMID- 22408272
TI  - Spinal analgesia for laparoscopic colonic resection using an enhanced recovery
      after surgery programme: better analgesia, but no benefits on postoperative
      recovery: a randomized controlled trial.
AB  - BACKGROUND: This study was undertaken to determine the impact of an intrathecal
      mixture of bupivacaine and morphine, when compared with systemic morphine, on the
      quality of postoperative analgesia and other outcomes in the context of the
      enhanced recovery after surgery (ERAS) programme for laparoscopic colonic
      resection. METHODS: Fifty patients undergoing general anaesthesia were randomly
      allocated to receive either a spinal mixture of bupivacaine and morphine followed
      by oral oxycodone (spinal group) or patient-controlled analgesia (PCA group). The
      primary outcome was consumption of opioids during the first three postoperative
      days. Secondary outcomes were pain scores, return of bowel function and dietary
      intake, readiness to hospital discharge, and length of hospital stay. RESULTS:
      Postoperative opioid consumption in the spinal group was significantly less over
      the first three postoperative days (P<0.001). The quality of analgesia at rest in
      the first 24 h was better in the spinal group (P<0.005). Excessive sedation and
      respiratory depression were reported in two elderly patients with spinal
      analgesia. There were no differences between the two groups in other outcomes
      (return of bowel function and dietary intake, readiness to hospital discharge,
      and length of hospital stay). CONCLUSIONS: When ERAS programme is used for
      laparoscopic colonic resection, an intrathecal mixture of bupivacaine and
      morphine was associated with less postoperative opioid consumption, but has no
      other advantages over systemic opioids.

PMID- 22408273
TI  - Prospective randomized comparison of ultrasound-guided and neurostimulation
      techniques for continuous interscalene brachial plexus block in patients
      undergoing coracoacromial ligament repair.
AB  - BACKGROUND: There are few data comparing the onset time of interscalene brachial
      plexus block performed using ultrasound (US) guidance or nerve stimulation (NS)
      technique for elective coracoacromial ligament repair. METHODS: Fifty ASA I-III
      patients were randomly allocated to receive a continuous interscalene brachial
      plexus block with 20 ml of 1% ropivacaine with either NS or US guidance. The time
      of block performance, number of skin punctures and needle redirections,
      inadvertent vascular punctures, and procedure-related pain scores were recorded.
      The onsets of sensory and motor blocks in the distribution of radial, axillary,
      and musculocutaneous nerves were blindly assessed every 5 min until 30 min from
      the end of local anaesthetic (LA) injection. Intraoperative fentanyl, general
      anaesthesia (GA) requirements, postoperative pain scores, LA consumption, and
      patients' requirements for subcutaneous morphine during the first 24 h were
      compared. RESULTS: Block onset times were similar. The time to complete the block
      and the number of skin punctures and vascular punctures were significantly lower
      in Group US. There were no differences in needle redirections, incidence of
      paraesthesiae, intraoperative fentanyl consumption, and requirements for GA or
      postoperative morphine. The US group required significantly less LA only at 16 h
      after surgery and had lower pain scores at rest at 24 h after surgery.
      CONCLUSIONS: Block onset times and success rate were similar whether NS or US was
      used, although US guidance allowed shorter procedural times, fewer needle
      punctures, and fewer vascular punctures.

PMID- 22408276
TI  - The production of oxygenated polycrystalline graphene by one-step ethanol
      chemical vapor deposition.
AB  - Large-area mono- and bilayer graphene films were synthesized on Cu foil (~ 1
      inch(2)) in about 1 min by a simple ethanol-chemical vapor deposition (CVD)
      technique. Raman spectroscopy and high resolution transmission electron
      microscopy revealed the synthesized graphene films to have polycrystalline
      structures with 2-5 nm individual crystallite size which is a function of
      temperature up to 1000 degrees C. X-ray photoelectron spectroscopy investigations
      showed about 3 atomic% carboxylic (COOH) functional groups were formed during
      growth. The field-effect transistor devices fabricated using polycrystalline
      graphene as conducting channel (L(c)=10 MUm; W(c)=50 MUm) demonstrated a p-type
      semiconducting behavior with high drive current and Dirac point at ~35 V. This
      simple one-step method of growing large area polycrystalline graphene films with
      semiconductor properties and easily functionalizable groups should assist in the
      realization of potential of polycrystalline graphene for nanoelectronics, sensors
      and energy storage devices.

PMID- 22408277
TI  - Estimating progression-free survival in paediatric brain tumour patients when
      some progression statuses are unknown.
AB  - In oncology, progression-free survival time, which is defined as the minimum of
      the times to disease progression or death, often is used to characterize
      treatment and covariate effects. We are motivated by the desire to estimate the
      progression time distribution on the basis of data from 780 paediatric patients
      with choroid plexus tumours, which are a rare brain cancer where disease
      progression always precedes death. In retrospective data on 674 patients, the
      times to death or censoring were recorded but progression times were missing. In
      a prospective study of 106 patients, both times were recorded but there were only
      20 non-censored progression times and 10 non-censored survival times.
      Consequently, estimating the progression time distribution is complicated by the
      problems that, for most of the patients, either the survival time is known but
      the progression time is not known, or the survival time is right censored and it
      is not known whether the patient's disease progressed before censoring. For data
      with these missingness structures, we formulate a family of Bayesian parametric
      likelihoods and present methods for estimating the progression time distribution.
      The underlying idea is that estimating the association between the time to
      progression and subsequent survival time from patients having complete data
      provides a basis for utilizing covariates and partial event time data of other
      patients to infer their missing progression times. We illustrate the methodology
      by analysing the brain tumour data, and we also present a simulation study.

PMID- 22408275
TI  - Progesterone can enhance consolidation and/or performance in spatial, object and
      working memory tasks in Long-Evans rats.
AB  - Progesterone has a ubiquitous role in reproduction and fitness and may influence
      cognitive performance. We examined the effects of administration of progesterone
      (a regimen that facilitates sexual behaviour) on consolidation of complex
      information in Long-Evans rats, Rattus norvegicus, that may be relevant for
      social engagement. We also examined the effects of subcutaneous progesterone
      administration (4 mg/kg versus oil vehicle placebo) on memory of ovariectomized
      rats during various cognitive tasks. Ovariectomized rats that received
      progesterone, versus the vehicle, immediately post-training were better able to
      find a hidden platform in the water maze. In a recognition task, rats that
      received progesterone spent more time in the novel arm of the Y-maze task than
      rats that received the vehicle. Ovariectomized rats that received progesterone
      immediately after training spent significantly more time exploring a novel object
      (compared to a familiar object) than did vehicle-administered rats. When socially
      relevant stimuli (i.e. objects with the scent of familiar or novel conspecifics)
      were used in the social cognition task, ovariectomized rats that received
      progesterone spent more time exploring the object with the novel conspecifics'
      scent than did vehicle-administered rats. Pairing of progesterone, but not the
      vehicle, conditioned a place preference to the originally nonpreferred side of
      the conditioning chamber. We found no significant differences in motor activity
      measures in these tasks due to progesterone treatment. These results suggest that
      progesterone's effects to improve cognitive processes with nonsocial and socially
      relevant stimuli, as well as have reinforcing effects, may underlie some of its
      salient effects on reproduction-related behaviours.

PMID- 22408278
TI  - Principled sure independence screening for Cox models with ultra-high-dimensional
      covariates.
AB  - It is rather challenging for current variable selectors to handle situations
      where the number of covariates under consideration is ultra-high. Consider a
      motivating clinical trial of the drug bortezomib for the treatment of multiple
      myeloma, where overall survival and expression levels of 44760 probesets were
      measured for each of 80 patients with the goal of identifying genes that predict
      survival after treatment. This dataset defies analysis even with regularized
      regression. Some remedies have been proposed for the linear model and for
      generalized linear models, but there are few solutions in the survival setting
      and, to our knowledge, no theoretical support. Furthermore, existing strategies
      often involve tuning parameters that are difficult to interpret. In this paper we
      propose and theoretically justify a principled method for reducing dimensionality
      in the analysis of censored data by selecting only the important covariates. Our
      procedure involves a tuning parameter that has a simple interpretation as the
      desired false positive rate of this selection. We present simulation results and
      apply the proposed procedure to analyze the aforementioned myeloma study.

PMID- 22408279
TI  - Age of word acquisition effects in treatment of children with phonological
      delays.
AB  - The effects of the age of acquisition (AoA) of words were examined in the
      clinical treatment of 10 preschool children with phonological delays. Using a
      single-subject multiple-baseline experimental design, children were enrolled in
      one of four conditions that varied the AoA of the treated words (early vs. late
      acquired) relative to their corresponding word frequency (high vs. low
      frequency). Phonological generalization to treated and untreated sounds in error
      served as the dependent variable. Results showed that late acquired words induced
      greater generalization, with an effect size four times greater than early
      acquired words, whereas the effects of word frequency were minimized. Results are
      discussed relative to hypotheses about the role of AoA in language acquisition
      and the relevance of this variable for phonological learning.

PMID- 22408280
TI  - Trivalent Iron Induced Gelation in Lambda-Carrageenan.
AB  - This communication reports gelation of lambda-carrageenan, for the first time, in
      the presence of trivalent iron ions. Kappa-, iota- and lambda-carrageenans are
      sulfated polysaccharides used extensively in food, pharmaceutical and medical
      applications. Kappa- and iota-carrageenans show gelation in the presence of mono-
      and di-valent ions, but lambda-carrageenan yields only viscous solutions. Our
      results show that gelation in lambda-carrageenan indeed is possible, but with
      trivalent ions. X-ray fiber diffraction patterns of iron (III)-lambda-carrageenan
      are characteristic of highly oriented and polycrystalline fibers containing well
      resolved Bragg reflections. The elastic modulus (G') of the product is far
      greater than the loss modulus (G") indicating the thermal stability of lambda
      carrageenan in the presence of iron (III) ions. This novel finding has potential
      to expand lambda-carrageenan's current utility beyond a viscosifying agent.

PMID- 22408281
TI  - The Influence of Topic Status on Written and Spoken Sentence Production.
AB  - Four experiments investigate the influence of topic status and givenness on how
      speakers and writers structure sentences. The results of these experiments show
      that when a referent is previously given, it is more likely to be produced early
      in both sentences and word lists, confirming prior work showing that givenness
      increases the accessibility of given referents. When a referent is previously
      given and assigned topic status, it is even more likely to be produced early in a
      sentence, but not in a word list. Thus, there appears to be an early mention
      advantage for topics that is present in both written and spoken modalities, but
      is specific to sentence production. These results suggest that information
      structure constructs like topic exert an influence that is not based only on
      increased accessibility, but also reflects mapping to syntactic structure during
      sentence production.

PMID- 22408282
TI  - Decision-making Strategies and Performance among Seniors.
AB  - Using paper and pencil experiments administered in senior centers, we examine
      decision-making performance in multi-attribute decision problems. We
      differentiate the effects of declining cognitive performance and changing
      cognitive process on decision-making performance of seniors as they age. We find
      a significant decline in performance with age due to reduced reliance on common
      heuristics and increased decision-making randomness among our oldest subjects.
      However, we find that increasing the number of options in a decision problem
      increases the number of heuristics brought to the task. This challenges the
      choice overload view that people give up when confronted with too much choice.

PMID- 22408283
TI  - Dispersion of aminoalkylsilyl ester or amine alkyl-phosphonic acid side wall
      functionalized carbon nanotubes in silica using sol-gel processing.
AB  - Aminopropyltriethoxysilane and aminopropyl-phosphonic ester modified carbon
      nanotubes were prepared by reacting fluorinated carbon nanotubes (F-CNTs) with
      the 3-aminopropyltriethoxysilane or 3-aminopropyl-phosphonic acid reagents at 120
      degrees C temperature, using pyridine as the base catalyst. These functionalized
      carbon nanotubes, APTES-CNTs, 1, and APPA-CNTs, 2, were characterized by
      transmission electron microscopy (TEM), infrared spectroscopy (IR), and
      thermogravimetric analysis (TGA). The homogeneous dispersion of these
      functionalized CNTs (0.1%) in silica were also accomplished by sol-gel
      processing. The TEM confirmed uniform dispersion of the functionalized CNT in
      silica.

PMID- 22408284
TI  - Material Hardship and Child Socioemotional Behaviors: Differences by Types of
      Hardship, Timing, and Duration.
AB  - Child behavior problems are associated with long-term detrimental effects. A
      large body of literature looks at the association between income and child
      behavior but few studies examine this association with material hardship, an
      alternative economic indicator. We use data from the Fragile Families and Child
      Wellbeing Study to examine the following questions: (a) Is material hardship
      associated with child socioemotional behavior and are there differences by
      developmental timing, (b) Are particular hardships (bills, utilities, food,
      housing, medical) more strongly associated with child behavior, and (c) Are there
      differences in the association between short-term and long-term material hardship
      and child behavior? We find that children in households experiencing material
      hardship score significantly higher on externalizing and internalizing behaviors.
      Additionally, we find that a mother's inability to pay bills, experience of
      utility interruption, and housing instability are adversely related to child
      behavior. We also find that the association between material hardship and child
      behaviors is stronger at age 5 and that chronic aggregate hardship has a stronger
      association with child behavior.

PMID- 22408285
TI  - Predicting Future PTSD using a Modified New York Risk Score: Implications for
      Patient Screening and Management.
AB  - AIM: We previously developed a posttraumatic stress disorder (PTSD) screening
      instrument - the New York PTSD Risk Score - that was effective in predicting
      PTSD. In the present study, we assessed a 12-month prospective version of this
      risk score, which is important for patient management, follow-up, and for
      emergency medicine.  METHODS: Using data collected in a study of New York City
      adults after the World Trade Center Disaster (WTCD), we developed a new PTSD
      prediction tool. Using diagnostic test methods, including receiver operating
      curve (ROC) and bootstrap procedures, we examined different prediction variables
      to assess PTSD status 12 months after initial assessment among 1,681 trauma
      exposed adults.  RESULTS: While our original PTSD screener worked well in the
      short term, it was not specifically developed to predict long-term PTSD. In the
      current study, we found that the Primary Care PTSD Screener (PCPS), when combined
      with psychosocial predictors from the original NY Risk Score, including
      depression, trauma exposure, sleep disturbance, and healthcare access, increased
      the area under the ROC curve (AUC) from 0.707 to 0.774, a significant improvement
      (p<0.0001). When additional risk-factor variables were added, including negative
      life events, handedness, self-esteem, and pain status, the AUC increased to
      0.819, also a significant improvement (p=0.001). Adding Latino and foreign status
      to the model further increased the AUC to 0.839 (p=0.007).  CONCLUSION: A
      prospective version of the New York PTSD Risk Score appears to be effective in
      predicting PTSD status 12 months after initial assessment among trauma-exposed
      adults. Further research is advised to further validate and expand these
      findings.

PMID- 22408286
TI  - CATALYTIC DYNAMIC RESOLUTION APPLIED TO THE SYNTHESIS OF 2,6-DISUBSTITUTED
      PIPERIDINES: PREPARATION OF (+)-LUPETIDINE AND (-)-EPIDIHYDROPINIDINE.
AB  - The diastereoselective synthesis of trans-2,6-disubstituted piperidines has been
      rendered enantioselective by incorporating a catalytic dynamic resolution into
      the first alkylation step. The method has been applied to the synthesis of (-)
      epidihydropinidine and (+)-trans-lupetidine.

PMID- 22408287
TI  - Examining the Sustainability of an Evidence-Based Preschool Curriculum: The REDI
      Program.
AB  - This study examined the extent to which an evidence-based preschool curriculum
      (Head Start REDI) was sustained by 20 teachers during the year following a
      randomized controlled efficacy trial, when teachers were no longer required by
      the research project to implement the curriculum. Two quantitative measures of
      sustainability (teacher ratings, REDI coach ratings) and a qualitative measure
      (teacher interview) were collected and compared. Sustainability varied by the
      specific curriculum component, with higher rates of sustainability for the social
      emotional component (Preschool PATHS) than for the language and literacy
      components. Estimates of sustainability were affected by the method of
      measurement, with REDI coach ratings and qualitative teacher interviews more
      closely aligned than teacher ratings. Responses from qualitative interviews
      identified the main factors that teachers thought affected sustainability.
      Teacher responses suggest that efforts to promote sustainability are best
      targeted at reducing barriers, such as competing demands, rather than simply
      highlighting the benefits of the new curriculum.

PMID- 22408288
TI  - Understanding Cortisol Reactivity across the Day at Child Care: The Potential
      Buffering Role of Secure Attachments to Caregivers.
AB  - Full-day center-based child care has been repeatedly associated with rising
      cortisol across the child care day. This study addressed the potential buffering
      role of attachment to mothers and lead teachers in 110 preschoolers while at
      child care. Using multi-level modeling and controlling for a number of child,
      family, and child care factors, children with more secure attachments to teachers
      were more likely to show falling cortisol across the child care day. Attachment
      to mothers interacted with child care quality, with buffering effects found for
      children with secure attachments attending higher quality child care.
      Implications for early childhood educators are discussed.

PMID- 22408289
TI  - Mode decomposition evolution equations.
AB  - Partial differential equation (PDE) based methods have become some of the most
      powerful tools for exploring the fundamental problems in signal processing, image
      processing, computer vision, machine vision and artificial intelligence in the
      past two decades. The advantages of PDE based approaches are that they can be
      made fully automatic, robust for the analysis of images, videos and high
      dimensional data. A fundamental question is whether one can use PDEs to perform
      all the basic tasks in the image processing. If one can devise PDEs to perform
      full-scale mode decomposition for signals and images, the modes thus generated
      would be very useful for secondary processing to meet the needs in various types
      of signal and image processing. Despite of great progress in PDE based image
      analysis in the past two decades, the basic roles of PDEs in image/signal
      analysis are only limited to PDE based low-pass filters, and their applications
      to noise removal, edge detection, segmentation, etc. At present, it is not clear
      how to construct PDE based methods for full-scale mode decomposition. The above
      mentioned limitation of most current PDE based image/signal processing methods is
      addressed in the proposed work, in which we introduce a family of mode
      decomposition evolution equations (MoDEEs) for a vast variety of applications.
      The MoDEEs are constructed as an extension of a PDE based high-pass filter
      (Europhys. Lett., 59(6): 814, 2002) by using arbitrarily high order PDE based low
      pass filters introduced by Wei (IEEE Signal Process. Lett., 6(7): 165, 1999). The
      use of arbitrarily high order PDEs is essential to the frequency localization in
      the mode decomposition. Similar to the wavelet transform, the present MoDEEs have
      a controllable time-frequency localization and allow a perfect reconstruction of
      the original function. Therefore, the MoDEE operation is also called a PDE
      transform. However, modes generated from the present approach are in the spatial
      or time domain and can be easily used for secondary processing. Various
      simplifications of the proposed MoDEEs, including a linearized version, and an
      algebraic version, are discussed for computational convenience. The Fourier
      pseudospectral method, which is unconditionally stable for linearized the high
      order MoDEEs, is utilized in our computation. Validation is carried out to mode
      separation of high frequency adjacent modes. Applications are considered to
      signal and image denoising, image edge detection, feature extraction, enhancement
      etc. It is hoped that this work enhances the understanding of high order PDEs and
      yields robust and useful tools for image and signal analysis.

PMID- 22408290
TI  - Estimating carnivoran diets using a combination of carcass observations and scats
      from GPS clusters.
AB  - Scat analysis is one of the most frequently used methods to assess carnivoran
      diets and Global Positioning System (GPS) cluster methods are increasingly being
      used to locate feeding sites for large carnivorans. However, both methods have
      inherent biases that limit their use. GPS methods to locate kill sites are biased
      towards large carcasses, while scat analysis over-estimates the biomass consumed
      from smaller prey. We combined carcass observations and scats collected along
      known movement routes, assessed using GPS data from four African lion (Panthera
      leo) prides in the Kruger National Park, South Africa, to determine how a
      combination of these two datasets change diet estimates. As expected, using
      carcasses alone under-estimated the number of feeding events on small species,
      primarily impala (Aepyceros melampus) and warthog (Phacochoerus africanus), in
      our case by more than 50% and thus significantly under-estimated the biomass
      consumed per pride per day in comparison to when the diet was assessed using
      carcass observations alone. We show that an approach that supplements carcass
      observations with scats that enables the identification of potentially missed
      feeding events increases the estimates of food intake rates for large
      carnivorans, with possible ramifications for predator-prey interaction studies
      dealing with biomass intake rate.

PMID- 22408292
TI  - Extending Ayurveda further....thinking beyond the possibilities....

PMID- 22408293
TI  - Prakriti-based medicine: A step towards personalized medicine.
AB  - The concept of personalized medicine has been around for as long as people have
      been practicing medicine. From Charaka to Hippocrates, all have practiced the
      personalized approach for treating a disease. In the 21(st) century, personalized
      medicine is all about DNA. Whereas the single nucleotide polymorphism (SNP) and
      epigenetic factors influence drug response and form the basis of personalized
      medicine, the tridosha theory forms the basis of Prakriti-based medicine. It is
      well established by now that western allopathic medicine is excellent in handling
      acute medical crises, whereas Ayurveda has successfully demonstrated an ability
      to manage chronic disorders that Western medicine has been unable to cure. With
      effective integration of 'omics' Prakriti-based medicine can play a vital role in
      this changing scenario of global health wisdom as Ayurveda offers its modalities
      by way of ahara (diet), vihara (lifestyle), and aushadhi (medication), which are
      the three pillars of prakriti-based medicine making it a holistic science.
      Prakriti-based medicine and other traditional medicine systems have the potential
      to offer remedies to the challenging health issues like adverse drug reactions,
      drug withdrawals, and economic disparities among few. An integrative global
      approach could do wonders to health sciences benefiting a broad spectrum of
      patients.

PMID- 22408294
TI  - Comparative studies of Bhanumati and Nibandha Samgraha with special reference to
      Arista Vijnana (prognostic science).
AB  - Ayurveda is serving the mankind for centuries with a holistic approach. This
      system has preached to treat the diseases which are only curable by the
      physicians. It has advised the physicians to strictly avoid treating the
      incurable diseases. In order to assess the incurability of the diseases or the
      incurable state of a patient; this system has preached the signs and symptoms of
      incurability which are known as arista-vijnana, which have been described in
      Brhattrayi of Ayurveda. Though Caraka has placed them in a separate section of
      his treatise, Cakrapani and Dalhana have also spent a considerable portion in
      their commentaries dealing with arista-vijnana. They were two renowned scholars
      who have commented with a depth of wisdom on Susruta Samhita. In this paper, the
      author has tried to present the comparative and critical comments of both
      commentators based on Bhanumati and Nibandha Samgraha, respectively, over arista
      vijnana as described in Sutrasthana of Susruta Samhita. Dalhana was greatly
      influenced by Caraka Samhita with regard to the prognostic science. On the other
      hand, Cakrapani repeatedly recognized the superiority of the indriya-sthana of
      Caraka Samhita with regard to analysis of prognostic science.

PMID- 22408295
TI  - A comprehensive outlook of Sannipata.
AB  - Nomenclature of the disease on the basis of vitiation of the body humors is
      stressed in ayurveda. Sannipatika, i.e., 'conglomeration of vitiated tridosa' is
      the final stage of process of manifestation of disease. In this specific state of
      pathogenesis, the disease becomes more advance and mostly irreversible. A
      detailed scientific study of Sannipatika-avastha has been documented in classics.
      Comprehensive analysis of sannipata-state and its ways of presentation is the
      main theme of the current article.

PMID- 22408296
TI  - A survey on etiopathological correlation of Krimi (intestinal helminths) and
      Pandu (anemia).
AB  - A survey study was aimed to find etiopathological status of intestinal helminths
      and also to accomplish its association with clinical condition Pandu. The survey
      samples included population of five schools and two localities in and around
      Jamnagar. The study was conducted on 337 subjects, of whom 36.20% cooperated to
      give stool samples to pathology laboratory; more than half of the samples
      surveyed were suffering with various parasitic infestations and one-third of the
      total subjects were found at risk to develop Pandu. Ascariasis patients were
      found in 71.14%, a potent cause of Pandu. Enterobius vermicularis was found in
      19.05%, while Hymenolepisnana in 6.35%. 77.77% were in the age group of 10 to 20
      years, 58.73% were male, 93.65% patients were Hindu, 80.95% of the patients had
      secondary level of education, dominancy of rural habitat was in 77.77%, and
      39.68% each were from lower and lower middle class.

PMID- 22408297
TI  - Evaluation of diet and life style in etiopathogenesis of senile dementia: A
      survey study.
AB  - Mind and body are inseparable entities and influences each other until death.
      Many factors such as stress, anxiety, depression, negative thoughts, unhealthy
      life style, unwholesome diet etc., disturb mental and physical wellbeing. Senile
      dementia is the mental deterioration, i.e, loss of intellectual ability
      associated with old age. It causes progressive deterioration of mental faculties,
      e.g., memory, intellect, attention, thinking, comprehension and personality, with
      preservation of normal level of consciousness. Two major types of senile dementia
      have been identified, namely that due to generalized atrophy in the cortical area
      of the brain (Alzheimer's type) and that due to vascular disorders mainly due to
      stroke. According to DSM-IV (diagnostic and statistical manual of mental
      disorders), the essential feature of dementia is the development of multiple
      cognitive deficits that include memory impairment and at least one of the
      following cognitive disturbances such as aphasia, apraxia, agnosia, or a
      disturbance in executive function. For the present study, a standardized
      questionnaire in the form of proforma incorporating types of foods (madhura, amla
      and lavana rasayukta ahara etc.) and life style (divaswapna, ratrijagarana and
      manasika bhavas etc) is prepared. To assess manasika bhava, Hamilton Anxiety
      Rating Scale, Hamilton Depression Rating Scale, Brief Psychiatry Rating Scale,
      and standardized gradations of anumana pariksha of manasika bhavas mentioned by
      Charaka at Vimana Sthana 4/8 were adopted. In this study, most of the patients
      had disturbed sleep, tendency to indulge in defective dietary habits and kapha
      vitiating diets and life style. On Hamilton Anxiety Rating Scale, patients had
      anxiety, tension, depression, difficulty in concentration, and memory. On
      Hamilton Depression Rating Scale, these patients had anxiety, depression, and
      hypochondriasis. On Brief Psychiatry Rating Scale, psychological factors affected
      include: anxiety, depression, somatic concern and tension, etc. The data reflects
      that unwholesome diet and disturbed mental health plays an important role in
      etiopathogenesis of senile dementia.

PMID- 22408298
TI  - Clinical evaluation of Vardhamana Pippali Rasayana in the management of Amavata
      (Rheumatoid Arthritis).
AB  - Amavata is described as a difficult to cure (Krichhrasadhya) disease in Ayurveda.
      Pain in joints with swelling is a cardinal feature of this disease. It can be
      correlated with rheumatoid arthritis described in modern medical science. In
      conventional medical science, steroids and some nonsteroidal anti-inflammatory
      drugs are used for its management, but they cause certain dangerous side effects
      in the patients. Ayurveda promises an excellent therapy for it. The present
      clinical trial was conducted with the same objective to provide a safe,
      economical and effective therapy to the patients of Amavata. The present study
      was conducted in 73 patients having classical symptoms of Amavata. The patients
      were given Vardhamana Pippali Rasayana for 15 days. Patients with any other acute
      or chronic systemic illness or infection were excluded from the study. The
      observations and results obtained were analyzed statistically applying the "t"
      test. All the patients experienced up to 50% relief from the signs and symptoms
      of Amavata after the therapy. The drug might have produced its beneficial effects
      in the patients of Amavata due to its Agnideepana, Amapachana, Vatashamaka and
      Rasayana effects in the body. A significant decrease in the erythrocyte
      sedimentation rate in all the patients was also noticed. All the results obtained
      were highly significant statistically. Thus, it can be implicated that the
      Vardhamana Pippali Rasayana has a lot of beneficial effects in the patients of
      Amavata.

PMID- 22408299
TI  - A study on Vasantika Vamana (therapeutic emesis in spring season) - A preventive
      measure for diseases of Kapha origin.
AB  - Panchakarma is the most essential part of Ayurveda treatments. It is preventive,
      preservative, promotive, curative and rehabilitative therapy. Ayurveda believes
      in strong relationship between macrocosm and microcosm and states that the
      seasonal changes will influence the biological systems resulting into the
      accumulation and aggravation of particular Dosha in a particular season like
      accumulation and aggravation of Kapha in Hemant Rutu (winter season) and Vasant
      Rutu (spring season) respectively, accumulation and aggravation of Pitta in
      Varsha Rutu (rainy season) and Sharad Rutu (autumn season) respectively.
      Vasantika Vamana is done in spring season approximately in the month of March and
      April for the elimination of vitiated Kapha Dosha which in turn helps to prevent
      the forth coming Kapha disorders and associated Pitta disorders or diseases
      originating or settled in the place of Kapha like bronchial asthma, allergic
      bronchitis, rhinitis, sinusitis, migraine, hyperacidity, indigestion, anorexia,
      obesity, overweight, dyslipidemia, diabetes mellitus, acne vulgaris, psoriasis,
      eczema, urticaria etc. In this study, a total of 89 persons were registered and
      69 volnteers/patients undergone classical Vamana Karma without any major
      complications. Average minimum, maximum, total dose and total days of Snehapana
      were 36.40 ml, 187.21 ml, 578.59 ml and 5.01 days respectively. Average quantity
      of Madanaphala, Ksheera, Yashtimadhu Phanta and Lavanodaka was 5.81 g, 1130.29
      ml, 3202.9 and 2489.13 ml respectively. The results were encouraging; hence,
      further studies may be conducted including large population in this direction.

PMID- 22408300
TI  - A clinical study of Devadarvyadi-Vati on Grahani Dosha in children.
AB  - Childhood period is considered as the period of rapid growth and development, as
      it is the crucial stage of establishing future. Gastro-intestinal disorders show
      high prevalence in pediatric practice. These conditions generally produce chronic
      illness. Grahanidosha is a disease related with Agnidushti. This condition is
      seen more in childhood period due to faulty dietary habit and changing lifestyle.
      The present paper deals with study on etiopathogenesis of Grahanidosha and
      evaluates the efficacy of Deavadarvyadi-Vati. The etiological factors and
      symptoms were observed carefully to make clear etiopathogenesis. Total 32
      patients (3-12 years) were registered and randomly divided into two groups. In
      Group A Devadarvyadi-Vati (treated group) and in Group B Bhunimbadi-Vati (control
      group) given for 4 weeks with Koshna Jala. In Group A (Devadarvyadi-Vati), marked
      improvement was observed in 21.43% of the patients, moderate improvement was
      observed in 57.14% of patients and mild improvement was observed in 21.43% of
      patients.

PMID- 22408301
TI  - A clinical study on the role of Ksara Vasti and Triphala Guggulu in Raktarsha
      (Bleeding piles).
AB  - Shonitarsha is a common affliction which has been described and treated since the
      beginning of human civilization. Hemorrhoidal cushions are a part of normal
      anatomy but become pathological when swollen or inflamed. Treatment of piles in
      modern medicine is hemorrhoidectomy which results in repeated recurrences.
      Ayurveda provides a cure and prevents recurrences. Present study was carried out
      using a combination of Apamarga Kshara Basti and Triphalaguggulu. The results of
      the clinical assessment of the indigenous formulation on 129 patients with
      bleeding piles are reported in this paper; 55 patients of a total of 129 showed
      marked relief.

PMID- 22408302
TI  - Protective effect of Yashtimadhu (Glycyrrhiza glabra) against side effects of
      radiation/chemotherapy in head and neck malignancies.
AB  - One of the very common side effects of Radiation/Chemotherapy especially of the
      head and neck malignancies is mucositis. Cancer therapy or the cancer itself may
      cause changes in the body chemistry that results in loss of appetite, pain,
      nausea, vomiting, diarrhea and very common mucositis which makes eating
      difficult. Loss of appetite is followed by an undesirable loss of weight due to
      insufficient amount of calories every day which can lead to loss of muscle mass
      and strength and other complications by causing interruptions of medical therapy,
      impeding effective cancer therapy. Mucositis cause decreased immunity and quality
      of life as well as poor tolerance to surgery and altered efficacy of Chemotherapy
      and Radiotherapy. The present study is designed with the objective to minimize
      the radiation induced mucositis, skin reaction, xerostomia, change in voice etc.
      with an Ayurvedic preparation Yashtimadhu Ghrita (processed ghee). Total 75
      patients were randomly divided into four groups and drugs were administered:
      Group A with local application of Yashtimadhu powder and honey in the oral cavity
      for few minutes prior to radiotherapy along with oral intake of Yashtimadhu
      Ghrita; Group B with only local application of the Yashtimadhu powder and honey
      in the oral cavity; Group C patients administered with only local application of
      honey in the oral cavity; Group D on conventional modern medication controlled
      group. All these patients under four groups had received Radiotherapy and
      Chemotherapy for maximum duration of 7 weeks. Mucositis and Skin reactions were
      observed in 100% of patients with varying degree. The intensity of Radiation and
      Chemotherapy induced mucositis was reduced to a great extent by the trial drug.
      Yashtimadhu (Glycyrrhiza glabra) can be used effectively in prevention and
      treatment of oral mucositis post radiation and chemotheraphy in patients of
      cancer, especially of the head and neck region. It proves beneficial in two ways:
      (i) there were no interruptions in the treatment, and (ii) food intake was not
      severely affected leading to maintenance of nutritional status of the patients.

PMID- 22408303
TI  - Conceptual and applied study of Snigdha and Ruksa Guna with special reference to
      Rasa-raktagata Sneha (hyperlipidemia).
AB  - Ayurveda as well as Philosophy accepted the Guna as the basic entity of the
      Sristi. The Maha Gunas, i.e., Sattva, Raja, and Tama are the prime energy, from
      where the universe evolves, along with human beings. Dravya and Guna both have a
      Samavayi relationship in which Gunas reside in Dravya and have a secondary place
      to it. Guna has multifold meanings according to its use, in social, cultural,
      philosophical, and literary fields. The concepts of Ayurveda are expressed with
      Gunas. Samanya and Visesa are usually expressed in terms of Gunas; the
      classification, description, and function of Dravyas depends upon Guna; Karmas
      are manifested forms of Guna and Samavaya is the eternal, intimate relation of
      Dravya and Guna. The principles like Triskandha (Hetu, linga, ousadhi) of
      Ayurveda also narrated by Gunas, Hetus are narrated in the terms of Guna; the
      Laksanas are the reflections in the status of Gunas of bodily elements, and
      Cikitsa is in the form of administration of Viparita Gunas. The increased
      elements are treated by opposite Guna. So if Ruksa Guna is increased then it is
      to be managed by Snigdha Guna and vice-versa. So diseases can be treated by
      applying the Gunas, and drugs for the required patient can be selected by
      applying these Gunas. In support of the above concept, a study on the persons of
      Rasa-raktagata Sneha (hyperlipidemia) has been carried out assuming that the
      condition is an increased state of Snigdha Guna and treatment is done using Ruksa
      property drugs. Patients were divided into two groups, i.e., treatment group
      (Ruksa Guna drugs) and control group (placebo). The results were assessed after
      45 days with the help of a specially prepared pro forma. All the important
      hematological, biochemical, and urine investigations were done. According to
      subjective and objective criteria, significant results were found for Group A as
      compared to Group B.

PMID- 22408304
TI  - Clinical effect of Nirgundi Patra pinda sweda and Ashwagandhadi Guggulu Yoga in
      the management of Sandhigata Vata (Osteoarthritis).
AB  - Sandhigata Vata is one among the 80 Nanatmaja Vata Vyadhies. Sandhigata Vata and
      Osteoarthritis have common symptoms, and hence, both are considered as similar
      entities by a majority of Ayurvedic scholars and same has been adopted here.
      Osteoarthritis is the most common joint disease among human beings today. In this
      study, a total of 116 patients were registered, out of them 101 patients had
      completed the full course of treatment, while 15 patients left against medical
      advice. The 101 patients of Sandhigata Vata were treated in two groups. Group A:
      In this group 50 patients of Sandhigata Vata were treated with Nirgundi Patra
      pinda sweda for 21 days and Ashwagandhadi Guggulu Yoga3 g/day for 45 days was
      given orally. Group B: In this group 51 patients of Sandhigata Vata were treated
      with only Ashwagandhadi Guggulu Yoga 3 g/day for 45 days. To assess the effect of
      the therapy objectively, all the signs and symptoms of Sandhigata Vata were given
      a score, depending upon their severity. Also functional tests like walking time,
      climbing stairs, and joint movement, were measured as a criteria for assessment.
      Both the groups showed good results, but Group B showed better results in
      comparison to group A.

PMID- 22408305
TI  - Efficacy of leech therapy in the management of osteoarthritis (Sandhivata).
AB  - Osteoarthritis (degenerative joint disease) is the most common joint disorder. It
      mostly affects cartilage. The top layer of cartilage breaks down and wears away.
      Osteoarthritis is of two types, primary (idiopathic) and secondary. In idiopathic
      osteoarthritis, the most common form of the disease, no predisposing factor is
      apparent. Secondary OA is pathologically indistinguishable from idiopathic OA but
      is attributable to an underlying cause. In Ayurveda the disease Sandhivata
      resembles with osteoarthritis which is described under Vatavyadhi. The NSAIDs are
      the main drugs of choice in modern medicine which have lots of side effects and
      therefore are not safe for long-term therapy. Raktamokshan, i.e., blood letting
      is one of the ancient and important parasurgical procedures described in Ayurveda
      for treatment of various diseases. Of them, Jalaukavacharana or leech therapy has
      gained greater attention globally, because of its medicinal values. The saliva of
      leech contains numerous biologically active substances, which have
      antiinflammatory as well as anesthetic properties. Keeping this view in mind we
      have started leech therapy in the patients of osteoarthritis and found
      encouraging results.

PMID- 22408306
TI  - Clinical efficacy of "Bhadra Mustadi Paste" and "Nagaradi Kwatha Gandusha" in
      Shitada (Gingivitis).
AB  - Shitada is one of the Dantamulagata Rogas mentioned by Acarya Susruta under the
      heading of Mukha Rogas. It is characterized by symptoms like spontaneous
      bleeding, halitosis, blackish discoloration of gums, and so on. The
      symptomatology of Shitada can be compared with gingivitis, which is caused mainly
      by the accumulation of debris, plaque, and calculus at the tooth margin due to
      ignorance of oral care. It can progress into periodontitis - the disease in which
      the firmness, contour, and position of the gums are altered and teeth become
      mobile. The prevalence of gingivitis is as high as 50% in most of the population.
      In the present study, a total of 33 patients were registered in three groups.
      Bhadramustadi yoga has been used in paste form for local application along with
      Nagaradi Kwatha Gandusa in Group A and in powder form for Pratisarana along with
      Nagaradi Kwatha Gandusa in Group B. In Group C (Control) Sphatika Jala was used.
      The patients were diagnosed and assessed on the basis of Ayurvedic as well as
      modern classical signs and symptoms. Further assessment was done with the
      different indices used in modern dentistry. All the signs and symptoms were given
      a score depending upon the severity, to assess the effect of the drugs
      objectively. The effect of therapy was highly significant in group A in most of
      the signs, symptoms, and indices; and in group B it was highly significant in
      some signs and symptoms.

PMID- 22408307
TI  - Comparative clinical evaluation of Kshara Sutra ligation and hemorrhoidectomy in
      Arsha (hemorrhoids).
AB  - Arsha (hemorrhoids) is engorgement of the hemorrhoidal venous plexus,
      characterized by bleeding per rectum, constipation, pain, prolapse and discharge.
      It is manifested due to improper diet, prolonged standing and faulty habits of
      defecation causing derangement of tridosha, mainly vata dosha. Vitiated dosha
      localizes in guda vali, pradhana dhamani and mansdhara kala and vitiates twak,
      mansa, meda and rakta, resulting in the annavaha sroto dushti. Modern management
      of arsha needs, mainly, a surgical approach, i.e. hemorrhoidectomy, wherein the
      result was found to be less satisfactory. In this regard, to determine a solution
      for satisfactory cure, the kshara sutra ligation method in arsha was studied in
      comparison with hemarrhoidectomy. Kshara sutra ligation in arsha was employed in
      35 patients, and 26 patients were dealt with hemorrhoidectomy. The study revealed
      a better result of the kshara sutra ligation-treated group in comparison with
      hemorrhoidectomy. The observations revealed that maximum advantages like minimum
      hospital stay, no bleeding during or after operation, no post-operative anal
      stenosis, a low cost-effective and more acceptable to different categories of
      people, etc. were recorded in the kshara sutra-treated group. Statistically,
      kshara sutra ligation for arsha was found to be highly significant and effective
      management. No adverse effects were noted during the follow-up period.

PMID- 22408308
TI  - Clinical evaluation of Kushmanda Ghrita in the management of depressive illness.
AB  - Depressive illness has been considered as a problematic mental illness since
      antiquity. The treatment modalities of depressive illness are of many kinds. Use
      of Medhya Rasayana drugs is a unique method of treatment described in Ayurveda
      for depressive illness. Kushmanda (Benincasa hispida) is one of the Medhya
      Rasayana as described by Bhava Mishra. Ghrita is also considered as Medhya
      Rasayana by almost all Acharyas. Keeping this background Kushmanda Ghrita has
      been selected as a trial drug to treat the patients of depressive illness. The
      study was carried out in 35 clinically diagnosed cases of depressive illness by
      using DSM-IV diagnostic criteria of depressive illness. All patients were given
      20 ml of Kushmanda Ghrita in two divided doses morning and evening with 40 ml of
      lukewarm water for a period of one month. It has shown statistically significant
      results with psychometric parameters-Hamilton depression rating scale (t = 24.36,
      P < 0.001), Hamilton anxiety rating scale (t = 26.20, P < .001), immediate memory
      span direct (t = 4.35, P < 0.001), and indirect test (t = 3.43, P < 01) along
      with clinical symptoms.

PMID- 22408309
TI  - Clinical evaluation of Basti administered by Basti Putak (Pressure method), Enema
      pot method (Gravity fed method), and syringe method in Kshinashukra
      (Oligozoospermia).
AB  - The objective of this study was to determine which method of administration of
      Basti is more efficacious. The study design was open randomized clinical trial
      and main outcome measures are Administration time, Retention time, Pervasion of
      Basti, Semenogram study, and Sexual parameters. The result: Sperm count was
      increased by 70.75% in Basti putak group and 54.07% in Enema pot group. Overall
      average retention time of Asthapana Basti and Anuvasana Basti was 1.5 times more
      in Basti putak group than the Enema pot group. The conclusion of this study was
      that Basti putak is more efficacious than Enema pot method.

PMID- 22408310
TI  - A clinical study on the role of Agnimanthadi compound in the management of
      Sthaulya (obesity).
AB  - Sthaulya (obesity) has become so common in the World's population that it is
      beginning to replace undernutrition and infectious diseases as the most
      significant contributor to ill health. It exacerbates a large number of health
      related problems, both independently and in association with other diseases.
      Therefore, this study was carried out at PG Hospital, IPGT and RA, Jamnagar to
      evaluate effect of Agnimanthadi compound in the patients of Sthaulya. For this
      purpose 83 patients of Sthaulya were selected out of which 15 patients were
      dropped out. Remaining 68 patients were treated in two groups. Among these, 38
      patients of Sthaulya were treated with Agnimanthadi compound administered orally
      in the dose of four capsules of 500 mg three times a day with lukewarm water
      before meal. Remaining 30 patients of Sthaulya were kept as placebo control and
      were administered orally two placebo capsules of 500 mg filled with starch, three
      times a day with lukewarm water before meal. The duration of the treatment in
      both the groups was 7 weeks with follow-up for 2 months. Analysis of overall
      effects of both the groups showed that Agnimanthadi compound provided markedly
      better reduction in weight, BMI and other signs and symptoms in the patients of
      obesity in comparison to the control group.

PMID- 22408311
TI  - Pharmacognostic evaluation of leaves of certain Phyllanthus species used as a
      botanical source of Bhumyamalaki in Ayurveda.
AB  - Today, World over, there is a great deal of interest in Ayurvedic system of
      medicine and thus the demand for various medicinal plants in the production of
      Ayurvedic medicines is ever increasing. Due to varied geographical locations
      where these plants grow, a great deal of adulteration or substitution is
      encountered in the commercial markets. Histological studies of the plant drugs
      are not only to study the adulterants but also are indispensable in accurate
      identification. Microscopic observations of the Phyllanthus species revealed the
      occurrence of anisocytic and paracytic type of stomata in Phyllanthus amarus ,
      while only anisocytic type of stomata is present in P. fraternus and P.
      maderaspatensis. Epidermal cell walls of P. amarus and P. fraternus are wavy and
      straight walled epidermal walls are observed in P. maderaspatensis. In India all
      the above-mentioned species of Phyllanthus are called "Bhumyamalaki" and they are
      being used in the treatment of various liver disorders. However, all the species
      of Phyllanthus doesn't have the active constituents responsible for the treatment
      of liver disorders. In the present investigation by using simple micro techniques
      accurate identification of different species of Phyllanthus has been established.

PMID- 22408312
TI  - Pharmacognostic evaluation of leaf of Cordia macleodii Hook., An ethnomedicinally
      important plant.
AB  - Plants of ethnomedicinal importance have contributed for the development of many
      new pharmacologically effective molecules/chemical entities to modern medicine.
      India, the country having one of the richest biodiversity of its flora in its
      forest, with numerous tribal inhabitants, is able to contribute a lot from
      ethnomedicine to the ailing humanity. Cordia macleodii Hook. (Boraginaceae), an
      ethnomedicinal plant has been highlighted for its wound healing, aphrodisiac and
      hepatoprotective activities. It is a medium-sized tree, known as Panki/Shikari by
      the tribals, rarely found in the forests of Orissa, Chhattisgarh and Madhya
      Pradesh. So far, the plant has been studied neither for its pharmacognostical
      characters nor for its pharmacological actions except its hepatoprotective
      activity. Hence, it has been selected for a detailed investigation which includes
      pharmacognostic study of its leaf to find out the diagnostic characters and
      preliminary physicochemical analysis. Results of the study will help in
      identifying the plant pharmacognostically. Presence of alkaloids, glycosides and
      tannins were found during the study.

PMID- 22408313
TI  - Evaluation of comparative free-radical quenching potential of Brahmi (Bacopa
      monnieri) and Mandookparni (Centella asiatica).
AB  - Ayurvedic texts describe rejuvenate measures called Rasayana to impart biological
      sustenance to bodily tissues. Rasayana acting specifically on brain are called
      Medhya Rasayana. Brahmi is one of the most commonly practiced herbs for the same.
      Yet there exist a controversy regarding the exact plant species among Bacopa
      monnieri L. Penn (BM) and Centella asiatica (L.) Urban (CA) to be used as Brahmi
      in the formulations. Though the current literature available has suggested a very
      good nootropic potential of both the drugs, none of the studies have been carried
      out on comparative potential of these herbs to resolve the controversy. Free
      radical scavenging potential for these plants is studied to find out their
      comparative efficacy. The study revealed a very good in vitro free-radical
      scavenging properties of aqueous and ethanolic extracts of both the plants as
      evidenced by FRAP, DPPH, reducing power, and antilipid peroxidation assays. It
      can be concluded from the studies that both the plants, although taxonomically
      totally different at family level, showed similar type of in vitro activities.
      The total phenolic and flavonoid contents also revealed a significant similarity
      in the two plants. The in vitro study supports the Ayurvedic concept of BM and CA
      having a similar potential.

PMID- 22408314
TI  - Preparation of dhatryarishta by dhatri swarasa and dhatri kwatha.
AB  - Dhatryarishta has been described for the first time in Charaka Samhita, in the
      context of Panduroga. The same reference is available in Chakradatta, Bhaishajya
      Ratnavali, and Sahastrayogam too. Generally Dhatri Swarasa [Amalaki (Emblica
      officinalis Gaertn.)] is used in the preparation of Dhatryarishta as per
      classical reference, but fresh Amalaki is not available in every season, so in
      the present study, Amalaki Kwatha (decoction) is used instead of Swarasa. A total
      of 13 batches of Dhatryarishta were prepared, out of which nine batches were
      prepared with Dhatri Swarasa and four batches with Dhatri Kwatha. For
      Dhatryarishta prepared by using Dhatri Swarasa, three methods were applied and in
      Dhatryarishta prepared by using Dhatri Kwatha two methods were applied. The study
      revealed that Dhatryarishta could only be prepared by using Amalaki Swarasa as
      quoted in the classics and not by using Amalaki Kwatha.

PMID- 22408315
TI  - Pro blood clotting activity of Scoparia dulcis in rats.
AB  - Scoparia dulcis Linn (Family: Scrophulariaceae, Sinhala: WalKoththamalli) is a
      perennial herb growing in many tropical countries including Sri Lanka.
      Traditional Physicians in rural down south areas apply crushed S. dulcis plant on
      cuts and bruises to stop bleeding. S. dulcis may also have Rakta Sthambhana
      property. The study on effect of decoction (water extract) of S. dulcis on blood
      clotting time in rats was carried out to investigate this. Two groups of rats, 12
      males and 42 females were used in this experimental study. Forty-two female rats
      were assigned into seven equal groups (n = 6/gp). Different doses of DE (25, 50,
      100, 1000, 1500 mg/kg) (group 1-5) or 2 ml of distilled water (DW) (group 6) were
      orally administered. 0.1 ml of vitamin K was injected intramuscularly (group 7)
      as reference drug to seventh the group. Twelve male rats were assigned into two
      equal groups (n = 6/gp), 2 ml of distilled water (DW) and doses of DE (1500
      mg/kg) were orally administered. Clotting time was determined on the Days 1, 2,
      and 7 using Lee and White method. In the DE treated groups with all doses, there
      was no reduction in clotting time on the Day 1 but a significant reduction of
      clotting time (P < 0.05) was observed on the Days 2 and 7. In the group treated
      with vitamin K, there was no significant reduction in clotting time on Day 1 or
      2, but there was a significant reduction in clotting time on Day 7. It is
      concluded that S. dulcis has proclotting activity (rakthasthambhana property) and
      this was faster than vitamin K.

PMID- 22408316
TI  - Immunomodulatory activity of Vachadhatryadi Avaleha in albino rats.
AB  - The present study is carried out to evaluate the immuno-modulatory activity of
      Vacha Dhatryadi Avaleha in albino rats. Vacha Dhatryadi Avaleha was prepared by
      classical method and evaluated for humoral antibody formation and cell-medicated
      immunity in established experimental models. Test formulation was administered at
      the dose of 900 mg/kg and parameters like hemagglutination titer, ponderal
      changes, histopathology of immunological organs and immunological paw edema were
      recorded. Vacha Dhatryadi Avaleha significantly enhanced antibody formation and
      moderately suppressed the immunological edema. The present study concludes that
      Vachadhatryadi Avaleha has immunopotentiating activity.

PMID- 22408317
TI  - The effect of Emblica officinalis diet on lifespan, sexual behavior, and fitness
      characters in Drosophila melanogaster.
AB  - Drosophila is an excellent organism to test Ayurvedic medicines. The objective of
      our study was to explore the potential of Emblica officinalis drug on longevity,
      sexual behavior, and reproductive fitness of Drosophila melanogaster using adult
      feeding method. Increase in the lifespan, fecundity, fertility, ovarioles number,
      and developmental time was observed in both parents and F1 generation, but not in
      the F2 generation in experimental culture (control + E. officinalis). According
      to the Duncan's multiple range test and ANOVA, there is a significant difference
      between two cultures. It was also noticed that E. officinalis influence some
      fitness characters in Drosophila along with sexual behavior.

PMID- 22408319
TI  - Certainty of forensic evidence.

PMID- 22408318
TI  - Ayurveda and herbs in dental health.

PMID- 22408320
TI  - Maintaining dental records: Are we ready for forensic needs?
AB  - CONTEXT: Dental remains are usually the last to get destroyed among body parts
      after death. They may be useful for personal identification in cases of mass
      disasters and decomposed unidentified bodies. Dental records may help in the
      identification of suspects in criminal investigations and in medicolegal cases.
      Maintenance of dental records is legally mandatory in most of the European and
      American countries. Unfortunately, the law is not very clear in India, and the
      awareness is very poor. AIMS: To assess the awareness regarding the dental record
      maintenance among dentists in Rajasthan, to deduce the quality of average dental
      records kept by them and to evaluate the potential use of their maintained
      records, in any of forensic or medicolegal cases. SETTINGS AND DESIGN: A cross
      sectional survey was conducted among 100 dental practitioners of different cities
      in Rajasthan, India. MATERIALS AND METHODS: Data were collected through a
      structured questionnaire, which was responded by the study population in the
      course of a telephonic interview. The questionnaire addressed on the mode of
      maintaining dental records in their regular practice. STATISTICAL ANALYSIS USED:
      The data so gathered were subjected for descriptive analysis. RESULTS: As for
      knowledge or awareness about maintaining dental records, surprisingly a very low
      percentile (about 38%) of surveyed dentists maintained records. Sixty-two percent
      of the dentists were maintaining no records at all. CONCLUSION: Nonmaintenance or
      poor quality of records maintained indicates that the dentists in Rajasthan are
      not prepared for any kind of forensic and medicolegal need if it arises.

PMID- 22408321
TI  - Sex determination by discriminant function analysis of palatal rugae from a
      population of coastal Andhra.
AB  - OBJECTIVE: The aim of the study was to investigate differences in the palatal
      rugae patterns in males and females of a cross-sectional hospital-based coastal
      Andhra population and application of discriminant function analysis in sex
      identification. MATERIALS AND METHODS: One hundred pre-orthodontic plaster casts,
      equally distributed between males and females belonging to an age range of 15-30
      years, were examined for different rugae patterns. Thomas classification was
      adopted for analysis. Association between rugae patterns and sexual dimorphism
      were tested using Unpaired t test, Chi square test and discriminant function
      analysis developed using SAS package. RESULTS: Difference in unification pattern
      among males and females was found to be statistically significant. The total
      number of the rugae was not statistically significant between the sexes.
      Association between rugae length and shape with sex determination was computed
      using discriminant analysis which enabled sex differentiation in this population
      with an accuracy of 78%. CONCLUSION: Palatal rugae revealed a specific pattern in
      unification among males and females of the coastal Andhra population.
      Discriminant function analysis enabled sex determination of individuals. However,
      these interpretations were precluded by the small sample size and further
      research work on larger samples and use of different classification systems is
      required to validate its use in forensic science.

PMID- 22408322
TI  - Awareness of forensic odontology among dental practitioners in Chennai: A
      knowledge, attitude, practice study.
AB  - OBJECTIVE: The aim of the study is to analyze the knowledge, attitude and
      practice of forensic odontology among dental practitioners in Chennai. MATERIALS
      AND METHODS: A cross-sectional study was conducted in a sample of 322 dental
      practitioners in Chennai and data was collected by means of a questionnaire.
      RESULTS: Twenty-one percent of the dental practitioners did not maintain dental
      records in their clinic/workplace, with only 12% of the practitioners maintaining
      complete records. Ninety-three percent of dental practitioners were not
      maintaining dental records for more than seven years. The significance of ante
      mortem records in identifying deceased suspects was not known to 17% of the
      dental practitioners. Forty percent of the dental practitioners were not aware of
      child abuse and the actions to be taken. Dental age estimation was not known to
      41% of the dental practitioners. Thirty-eight percent of the practitioners were
      unaware of the accurate method of individual identification. About 18% of the
      dental practitioners did not know the significance of bite mark patterns of the
      teeth. Ninety-three percent of the practitioners lacked formal training in
      collecting, evaluating and presenting dental evidence. Thirty percent of dental
      practitioners did not know they can testify as an expert witness in the court of
      law. Forty percent of the dental practitioners were unaware of identifying the
      age and gender of an individual in mass disasters. CONCLUSION: Our study revealed
      inadequate knowledge, poor attitude and lack of practice of forensic odontology
      prevailing among the dental practitioners in Chennai.

PMID- 22408323
TI  - Cheiloscopy: An aid for personal identification.
AB  - AIM: Cheiloscopy is a forensic investigation technique that deals with
      identification of humans based on lips traces. The aim of this study is to
      establish the uniqueness of lip prints which aids in personal identification.
      MATERIALS AND METHODS: The study group comprised of 200 subjects. The materials
      used were dark-colored lipstick, paper, cellophane tape, a brush, and a
      magnifying lens. RESULTS: This study shows that lip prints are unique and
      permanent for each individual, and the lip prints among family members and
      between twins revealed different patterns on the whole with few similar grooves
      suggesting the existence of heredity in the lip prints. CONCLUSION: Our study
      showed that lip prints are unique to each individual and can be used for personal
      identification.

PMID- 22408324
TI  - Efficacy of various materials in recording enamel rod endings on tooth surface
      for personal identification.
AB  - AIM: To analyze efficacy of cellulose acetate film, cellophane tape, and light
      body impression material in recording enamel rod endings on tooth surface for
      personal identification. MATERIALS AND METHODS: Surface enamel rod endings of 30
      extracted teeth were recorded from the same area of the same tooth for two times
      using cellulose acetate film, cellophane tape, and light body impression
      material. Photomicrographs of enamel rod endings were taken and subjected to
      Verifinger standard SDK version 5.0 software for analysis. Minutiae scores of all
      enamel rod end patterns obtained using these three imprint materials were
      statistically analyzed. RESULTS: Cellulose acetate film imprint showed complete
      enamel rod end patterns and the software was able to identify the particular
      tooth with the same previous identification number in subsequent recordings as
      well. Cellophane tape and light body rubber-base impression material imprint
      showed incomplete enamel rod end patterns and the software failed to identify the
      particular tooth with the same previous identification number in subsequent
      recordings. Statistical analysis revealed that cellulose acetate film recorded
      more number of minutiae points compared with the other imprint materials.
      CONCLUSION: Cellulose acetate film is a reliable material for recording enamel
      rod endings on tooth surface for personal identification compared with cellophane
      tape and light body rubber-base impression material.

PMID- 22408325
TI  - Cheiloscopy and its patterns in comparison with ABO blood groups.
AB  - OBJECTIVE: The aim of this study is to determine the distribution of different
      lip print patterns among subjects having different ABO and Rh blood groups and to
      determine the correlation between their characters and blood groups. MATERIALS
      AND METHODS: The present study was done on 150 individuals who were randomly
      selected and blood groups of these subjects were analyzed. RESULTS: The results
      revealed no association between distribution of lip print (cheiloscopy) pattern
      and blood groups. CONCLUSION: Lip print pattern does not show any correlation
      between blood groups.

PMID- 22408326
TI  - Sex determination using mesiodistal dimension of permanent maxillary incisors and
      canines.
AB  - BACKGROUND: Sexual dimorphism refers to the differences in size, shape, etc.,
      between males and females. The dentition's use in sex assessment has been
      explored and advocated owing to its strength and resistance to peri- and post
      mortem insults. OBJECTIVES: The study evaluated permanent maxillary incisors and
      canines for sexual dimorphism and estimated the level of accuracy with which they
      could be used for sex determination. MATERIALS AND METHODS: The study was
      conducted on 100 subjects (50 males, 50 females). The mesiodistal dimension of
      permanent maxillary incisors and canines was measured and the data were subjected
      to statistical analysis. RESULT: Univariate analysis revealed that all permanent
      maxillary incisors and canines exhibited larger mean values of mesiodistal
      dimension in males compared to females but only canines were found to be
      statistically significant for sexual dimorphism. CONCLUSION: The study showed
      maxillary canines exhibiting significant sexual dimorphism and can be used for
      sex determination along with other procedures.

PMID- 22408327
TI  - Dimensional analysis of various rugae patterns in north Indian population subset.
AB  - INTRODUCTION: Rugae patterns are significant markers for analyzing
      anteroposterior changes in adolescence, and forensic investigations. AIM: The
      purpose of this study was to ascertain the gender-wise predisposition of rugae
      patterns and to analyze anteroposterior alterations along with any developmental
      changes in palatal depth. MATERIALS AND METHODS: One hundred pre-treatment study
      cast models were obtained from the archives of the Department of Orthodontics,
      M.M. CDSR, Mullana. Parameters employed were: Division of medial palatal region
      into "a": Distance between incisive papilla length and anterior limit of the
      anteriormost rugae; "b": Distance between incisive papilla and most posterior
      rugae limits; measurement of Lateral rugae dimensions and palatal depth.
      STATISTICAL ANALYSIS: Mean +/- S.D. values were obtained and 'P' values
      calculated. RESULTS: Comparison of "a" and "b" showed a significant difference in
      the P values between the age-groups 12-13 years and >14 years. Rugae patterns
      with separate origins showed a predisposition for female gender. CONCLUSION: A
      significant change in the anteroposterior medial rugae dimensions was seen in
      adolescent age groups alongside no variation in palate depth. Hence, it can be
      concluded that differential growth potential is present in the premaxilla and can
      cause shift in medial palatal dimensions without altering the rugae patterns and
      palatal depth.

PMID- 22408328
TI  - The use of insects in forensic investigations: An overview on the scope of
      forensic entomology.
AB  - Forensic entomology is the study of insects/arthropods in criminal investigation.
      Right from the early stages insects are attracted to the decomposing body and may
      lay eggs in it. By studying the insect population and the developing larval
      stages, forensic scientists can estimate the postmortem index, any change in
      position of the corpse as well as the cause of death. Forensic odontologists are
      called upon more frequently to collaborate in criminal investigations and hence
      should be aware of the possibilities that forensic entomology have to offer and
      use it as an adjunct to the conventional means of forensic investigation.

PMID- 22408329
TI  - A simple and inexpensive bar-coding technique for denture identification.
AB  - A number of commercial methods for identifying dentures are available. They can
      be either invasive or noninvasive techniques. The less sophisticated procedures
      include simple engraving with bur, and more sophisticated procedures use labels
      or chips. Bar coding system is a way of transferring data to the computer and
      huge data can be stored as a record. Bar coding can be easily incorporated during
      acrylization of the denture and thus could be used in individual identification.

PMID- 22408330
TI  - Accuracy of radiographic methods in dental age estimation.

PMID- 22408331
TI  - Reactive oxygen species, anti-oxidant enzymes and smoldering chronic
      inflammation: Relevance to diabetes mellitus, atherosclerosis, and menopausal
      metabolic syndrome.

PMID- 22408332
TI  - Exercise beyond menopause: Dos and Don'ts.
AB  - With a significant number of women belonging to the status of menopause and
      beyond, it is imperative to plan a comprehensive health program for them,
      including lifestyle modifications. Exercise is an integral part of the strategy.
      The benefits are many, most important being maintenance of muscle mass and
      thereby the bone mass and strength. The exercise program for postmenopausal women
      should include the endurance exercise (aerobic), strength exercise and balance
      exercise; it should aim for two hours and 30 minutes of moderate aerobic activity
      each week. Every woman should be aware of her target heart rate range and should
      track the intensity of exercise employing the talk test. Other deep breathing,
      yoga and stretching exercises can help to manage the stress of life and menopause
      related symptoms. Exercises for women with osteoporosis should not include high
      impact aerobics or activities in which a fall is likely. The women and the
      treating medical practitioner should also be aware of the warning symptoms and
      contraindications regarding exercise prescription in women beyond menopause. The
      role of exercise in hot flashes, however, remains inconclusive. Overall,
      exercising beyond menopause is the only noncontroversial and beneficial aspect of
      lifestyle modification and must be opted by all.

PMID- 22408333
TI  - Stress urinary incontinence: What, when, why, and then what?
AB  - Stress urinary incontinence (SUI) has a significant impact on the quality of life
      for many women. Most women do not seek medical attention for this condition.
      Treatment for this problem includes initial conservative therapies and then
      surgery is an option. More than 200 surgical procedures have been described in
      the literature for the treatment of stress incontinence. The gold-standard
      surgical treatment of SUI in patients with a mobile bladder neck and normally
      functioning urethra has been accomplished through a retropubic approach using
      either a Burch or Marshall-Marchetti-Krantz procedure. By the absolute success of
      Trans obturator tape (TOT) application in treatment of SUI and the niche it has
      created for itself in the maze of treatment modalities available for SUI, there
      seems to be little doubt that TOT is all set to become the new Gold Standard for
      treatment of SUI in times to come. It is difficult to imagine any further
      improvements in the midurethral sling procedures or surgeries for SUI. However 10
      years ago, no one could have imagined the progress and development that has been
      seen over these few short years in the treatment of SUI. The future may hold
      promise in technologies such as stem cells that may be injected in or around the
      urethral support structures and provide regeneration of the lacking support
      structures. What so ever, it's definitely time to provide millions of women with
      knowledge that empowers them to make lifestyle changes to decrease their risk of
      SUI and to understand the reality that they are not alone if they have SUI.

PMID- 22408334
TI  - Lumbar spinal mobility changes among adults with advancing age.
AB  - BACKGROUND: Limitations in spinal mobility can interfere with the attainment of
      important functional skills and activities of daily living and restrictions in
      spinal mobility are usually the earliest and reliable indicator of diseases.
      OBJECTIVE: The aim of this study was to determine the differences of lumbar
      spinal mobility among healthy adults with advancing age. MATERIALS AND METHODS:
      The modified Schober's method was used to measure anterior flexion. The guideline
      of the American Academy of Orthopaedic Surgeons was adapted to measure lateral
      flexion and extension. RESULTS: The results of this study indicate that spinal
      mobility decreases with advancing age. The most significant (P < 0.05)
      differences occurred between the two youngest and the two oldest age categories.
      CONCLUSION: Using these data, we developed normative values of spinal mobility
      for each sex and age group. This study helps the clinicians to understand and
      correlate the restrictions of lumbar spinal mobility due to age and differentiate
      the limitations due to disease.

PMID- 22408335
TI  - Glutathione peroxidase activity in obese and nonobese diabetic patients and role
      of hyperglycemia in oxidative stress.
AB  - BACKGROUND: Both hyperglycemia and obesity are known to cause oxidative stress,
      which leads to many complications associated with diabetes mellitus. A large
      number of diabetic patients are obese. Glutathione peroxidase (GPx) is an
      important indicator of level of oxidative stress. MATERIALS AND METHODS: In the
      present study, we assessed GPx levels in 20 healthy controls, obese, and nonobese
      diabetic patients (n=20 each) and analyzed the effect of insulin treatment for 24
      and 48 weeks on GPx activity. GPx activity was measured using biochemical method.
      The GPx activity was also correlated with glycemic status of obese and nonobese
      diabetic patients [fasting plasma glucose (FPG) levels] after insulin therapy.
      Statplus software was used for statistical analysis. RESULTS: We found that there
      is suppression of GPx activity in diabetic patients as compared to healthy
      controls (70.9 +/- 9.6 U/mg protein) and suppression is more in case of obese
      (23.4 +/- 3.8 U/mg protein) than nonobese diabetics (41.5 +/- 3.5 U/mg protein).
      Both obese (26.05 +/- 4.03 U/mg protein) and nonobese (48.7 +/- 4.8 U/mg protein)
      diabetics had increase in GPx activity after 24 weeks of insulin treatment.
      Further, insulin treatment led to improvement in oxidative stress after 48 weeks
      in both obese (28.4 +/- 6.4) as well as nonobese diabetics (51.8 +/- 5.4). The
      nonobese group showed extremely significant (P<0.001) increase in GPx activity
      after 24 and 48 weeks both, while obese group showed significant (P value<0.05)
      increase in GPx activity with insulin treatment only after 48 weeks. A negative
      correlation was found between postinsulin GPx levels and FPG of obese and
      nonobese diabetics. The correlation was more strong in case of nonobese than
      obese diabetics. CONCLUSION: Higher levels of oxidative stress in obese diabetics
      even after control of hyperglycemia by insulin treatment reflect the importance
      of obesity in contributing to oxidative stress.

PMID- 22408336
TI  - Sexual function among married menopausal women in Amol (Iran).
AB  - BACKGROUND: Sexual activity is an important part of the human being's life but
      this instinct could be influenced by some factors such as diseases, drug using,
      aging, and menopause. But information about that is limited. AIM: The aim of this
      study is to determine the status of sexual activity among married menopausal
      women in Amol, Iran. MATERIALS AND METHODS: This descriptive analytical study was
      conducted to describe the sexual activity and sexual dysfunction of women after
      menopause. Data were collected from health centers in Amol from 280 married women
      using a questionnaire (self-completed or by interview). FINDING: Mean age of
      subjects were 55.9 +/- 6.02 years. 23.4% of subjects reported that their sexual
      intercourse had been low. 70% of subjects reported a decrease in their sexual
      activities after menopause. Sexual dysfunctions includes sexual desire disorder
      80% arousal dysfunction 80%, orgasmic dysfunction 25%, dyspareunia 55.6%, and
      lack of sexual satisfaction 43.2%. CONCLUSION: Findings revealed high percentage
      of sexual desire disorder and sexual arousal disorder in menopausal women.
      Therefore, we should have emphasis on counseling and education about sexual
      activities during the menopause period.

PMID- 22408337
TI  - Prevalence and related risk factors of osteoporosis in peri- and postmenopausal
      Indian women.
AB  - AIM: We undertook this study involving 200 peri- and postmenopausal women to
      determine the prevalence of osteoporosis, and in turn increase the awareness,
      education, prevention, and treatment of osteoporosis. SETTING AND DESIGN:
      Postgraduate Institute of Medical Education and Research, UT Chandigarh, India,
      and a clinical study. MATERIALS AND METHODS: A detailed medical, obstetrical,
      menstrual, and drug history was recorded in a proforma designated for the study.
      Height and weight was measured, weight-bearing exercise was assessed, and
      sunlight exposure per day for each woman was recorded. Food intake was estimated
      by using the 24-hour dietary recall method, and calcium and vitamin D consumption
      pattern was assessed. Bone mineral density (BMD) at postero-anterior lumbar spine
      and dual femurs was assessed by densitometer. Women were classified according to
      the WHO criteria. STATISTICAL ANALYSIS USED: Student's t-test, multiple logistic
      regression analysis. RESULTS: The prevalence of low BMD was found in more than
      half of this population (53%). The mean age in group I (normal BMD) was found to
      be 50.56 +/- 5.74 years as compared to 52.50 +/- 5.94 in group II with low BMD
      (P=0.02). The two groups were similar with respect to parity, education,
      socioeconomic status, family history of osteoporosis, hormone replacement
      therapy, and thyroid disorders. 46.8% of the women in group I and 33% of the
      women in group II had low physical activity and there was no statistically
      significant difference in sunlight exposure between the groups. Parity or the
      number of children and type of menopause was not seen to have much association
      with low BMD in our study. Lack of exercise and low calcium diet were
      significantly associated with low BMD. Multiple logistic regression analysis
      showed that age, exercise, menopause, and low calcium diet acted as significant
      predictors of low bone density. CONCLUSION: The findings from the study suggest
      the need for large community-based studies so that high-risk population can be
      picked up and early interventions and other life style changes can be instituted
      if there is delay in implementing national or international health strategies to
      tackle this increasing global health problem. Strategies to identify and manage
      low BMD in the primary care setting need to be established and implemented.

PMID- 22408338
TI  - Delayed menopause due to granulosa cell tumor of the ovary.
AB  - A 52-year-old patient presented with complaints of menorrhagia. Endometrial
      biopsy revealed simple hyperplasia of the endometrium. Total abdominal
      hysterectomy with bilateral oophorectomy was carried out. The ovaries looked
      grossly normal, but histopathology reported granulosa cell tumor of the right
      ovary. Granulosa cell tumors belong to the sexcord stromal category and account
      for approximately 2% of all ovarian tumors. We review the features and treatment
      of granulosa cell tumors and the importance of screening for ovarian tumors in a
      case of endometrial hyperplasia and delayed menopause.

PMID- 22408339
TI  - Basal cell carcinoma of the nipple areola complex.
AB  - Basal cell carcinoma (BCC) of the breast is a rare occurrence. To the best of our
      knowledge, only 34 cases of this rare malignancy have been reported worldwide. We
      report the case of a 48 year old lady who presented with history of rapid
      enlargement of a nevus over breast since three months. On initial examination a
      diagnosis of melanoma was considered. However the histopathology showed features
      suggestive of BCC. This case report highlights an atypical presentation of BCC.

PMID- 22408340
TI  - Management of pressure ulcers - What is new?
AB  - Pressure ulcers (PUs) are an important aspect of geriatrics and palliative care
      that amplifies morbidity of the chronically bed-ridden patients posing a threat
      to health-care economy and resources. PUs can interfere with functional recovery,
      may be complicated by pain and infection and can prolong hospital length of stay.
      Their presence may be a marker of poor overall prognosis and premature mortality.
      The pathogenesis and progress in the management of PUs is discussed.

PMID- 22408341
TI  - Mid-Session Indian Menopause Society, Governing Council Meeting Workshop,
      Lucknow, 2011: Urogynecology and reconstructive pelvic surgery skills, important
      armamentorium in menopause healthcare: A report.

PMID- 22408342
TI  - Therapeutic goal of diabetes mellitus.

PMID- 22408343
TI  - Self-administered osteoporosis risk score.

PMID- 22408344
TI  - Antimicrobial management of intra-abdominal infections: literature's guidelines.
AB  - Antimicrobial management of severe intra-abdominal infections (IAIs) involves a
      delicate balance of optimizing empirical therapy, which has been shown to improve
      clinical outcomes, while simultaneously reducing unnecessary antimicrobial use.
      Two sets of guidelines for the management of intra-abdominal infections were
      recently published. In 2010, the Surgical Infection Society and the Infectious
      Diseases Society of America (SIS-IDSA) created guidelines for the diagnosis and
      management of complicated IAIs. The new SIS-IDSA guidelines replace those
      previously published in 2002 and 2003. The World Society of Emergency Surgery
      (WSES) guidelines represent additional contributions, made by specialists
      worldwide, to the debate regarding proper antimicrobial drug methodology. These
      guidelines represent the conclusions of the consensus conference held in Bologna,
      Italy, in July 2010 during the first congress of the WSES.

PMID- 22408345
TI  - Evaluation of inflammatory activity in Crohn's disease and ulcerative colitis.
AB  - Crohn's disease and ulcerative colitis evolve with a relapsing and remitting
      course. Determination of inflammatory state is crucial for the assessment of
      disease activity and for tailoring therapy. However, no simple diagnostic test
      for monitoring intestinal inflammation is available. Noninvasive markers give
      only indirect assessments of disease activity. Histopathological or endoscopical
      examinations accurately assess inflammatory activity, but they are invasive, time
      consuming and expensive and therefore are unsuitable for routine use. Imaging
      procedures are not applicable for ulcerative colitis. The usefulness of
      ultrasound and Doppler imaging in assessing disease activity is still a matter of
      discussion for Crohn's disease, and an increased interest in computed tomography
      enterograph (CTE) has been seen, mainly because it can delineate the extent and
      severity of bowel wall inflammation, besides detecting extraluminal findings.
      Until now, the available data concerning the accuracy of magnetic resonance
      enterography in detecting disease activity is less than CTE. Due to this,
      clinical activity indices are still commonly used for both diseases.

PMID- 22408346
TI  - DNA methylation and microRNAs in cancer.
AB  - DNA methylation is a type of epigenetic modification in the human genome, which
      means that gene expression is regulated without altering the DNA sequence.
      Methylation and the relationship between methylation and cancer have been the
      focus of molecular biology researches. Methylation represses gene expression and
      can influence embryogenesis and tumorigenesis. In different tissues and at
      different stages of life, the level of methylation of DNA varies, implying a
      fundamental but distinct role for methylation. When genes are repressed by
      abnormal methylation, the resulting effects can include instability of that gene
      and inactivation of a tumor suppressor gene. MicroRNAs have some aspects in
      common with this regulation of gene expression. Here we reviewed the influence of
      gene methylation on cancer and analyzed the methods used to profile methylation.
      We also assessed the correlation between methylation and other epigenetic
      modifications and microRNAs. About 55,845 research papers have been published
      about methylation, and one-fifth of these are about the appearance of methylation
      in cancer. We conclude that methylation does play a role in some cancer types.

PMID- 22408347
TI  - Endoscopic ultrasound-guided elastography in the nodal staging of oesophageal
      cancer.
AB  - AIM: To assess quantitative endoscopic ultrasound (EUS)-guided elastography in
      the nodal staging of oesophago-gastric cancers. METHODS: This was a single
      tertiary centre study assessing 50 patients with established oesophago-gastric
      cancer undergoing EUS-guided fine needle aspiration biopsy (FNAB) of lymph nodes
      between July 2007 and July 2009. EUS-guided elastography of lymph nodes was
      performed before EUS-FNAB. Standard EUS characteristics were also described.
      Cytological determination of whether a lymph node was malignant or benign was
      used as the gold standard for this study. Comparisons of elastography and
      standard EUS characteristics were made between the cytologically benign and
      malignant nodes. The main outcome measure was the accuracy of elastography in
      differentiating between benign and malignant lymph nodes in oesophageal cancers.
      RESULTS: EUS elastography and FNAB were performed on 53 lymph nodes. Cytological
      malignancy was found in 23 nodes, one was indeterminate, one was found to be a
      gastrointestinal stromal tumor and 25 of the nodes were negative for malignancy.
      On 3 occasions insufficient material was obtained for analysis. The area under
      the curve for the receiver operating characteristic curve for elastography strain
      ratio was 0.87 (P < 0.0001). Elastography strain ratio had a sensitivity 83%,
      specificity 96%, positive predictive value 95%, and negative predictive value 86%
      for distinguishing between malignant and benign nodes. The overall accuracy of
      elastography strain ratio was 90%. Elastography was more sensitive and specific
      in determining malignant nodal disease than standard EUS criteria. CONCLUSION:
      EUS elastography is a promising modality that may complement standard EUS and
      help guide EUS-FNAB during staging of upper gastrointestinal tract cancer.

PMID- 22408348
TI  - Histotype-based prognostic classification of gastric cancer.
AB  - AIM: To test the efficiency of a recently proposed histotype-based grading system
      in a consecutive series of gastric cancers. METHODS: Two hundred advanced gastric
      cancers operated upon in 1980-1987 and followed for a median 159 mo were
      investigated on hematoxylin-eosin-stained sections to identify low-grade
      [muconodular, well differentiated tubular, diffuse desmoplastic and high lymphoid
      response (HLR)], high-grade (anaplastic and mucinous invasive) and intermediate
      grade (ordinary cohesive, diffuse and mucinous) cancers, in parallel with a
      previously investigated series of 292 cases. In addition, immunohistochemical
      analyses for CD8, CD11 and HLA-DR antigens, pancytokeratin and podoplanin, as
      well as immunohistochemical and molecular tests for microsatellite DNA
      instability and in situ hybridization for the Epstein-Barr virus (EBV) EBER1 gene
      were performed. Patient survival was assessed with death rates per 100 person
      years and with Kaplan-Meier or Cox model estimates. RESULTS: Collectively, the
      four low-grade histotypes accounted for 22% and the two high-grade histotypes for
      7% of the consecutive cancers investigated, while the remaining 71% of cases were
      intermediate-grade cancers, with highly significant, stage-independent, survival
      differences among the three tumor grades (P = 0.004 for grade 1 vs 2 and P =
      0.0019 for grade 2 vs grade 3), thus confirming the results in the original
      series. A combined analysis of 492 cases showed an improved prognostic value of
      histotype-based grading compared with the Lauren classification. In addition, it
      allowed better characterization of rare histotypes, particularly the three
      subsets of prognostically different mucinous neoplasms, of which 10 ordinary
      mucinous cancers showed stage-inclusive survival worse than that of 20
      muconodular (P = 0.037) and better than that of 21 high-grade (P < 0.001) cases.
      Tumors with high-level microsatellite DNA instability (MSI-H) or EBV infection,
      together with a third subset negative for both conditions, formed the T8 cell
      rich HLR group, the largest group among low-grade histotypes. Coexisting HLR
      proved to be a factor in improved prognosis in tumors with microsatellite
      instability (P = 0.0015 vs HLR-/MSI-H tumors) or DR type human leukocyte antigen
      expression (P = 0.033 vs HLR-/HLA-DR+ tumors). CONCLUSION: Identification of low-
      and high-grade histotypes can improve the prognostic assessment of a substantial
      proportion of gastric cancers in routine diagnostic practice.

PMID- 22408349
TI  - Low-dose steroid pretreatment ameliorates the transient impairment of liver
      regeneration.
AB  - AIM: To determine if liver regeneration (LR) could be disturbed following
      radiofrequency (RF) ablation and whether modification of LR by steroid
      administration occurs. METHODS: Sham operation, partial hepatectomy (PH), and
      partial hepatectomy with radiofrequency ablation (PHA) were performed on adult
      Fisher 344 rats. We investigated the recovery of liver volume, DNA synthetic
      activities, serum cytokine/chemokine levels and signal transducers and activators
      of transcription 3 DNA-binding activities in the nucleus after the operations.
      Additionally, the effects of steroid (dexamethasone) pretreatment in the PH group
      (S-PH) and the PHA group (S-PHA) were compared. RESULTS: The LR after PHA was
      impaired, with high serum cytokine/chemokine induction compared to PH, although
      the ratio of the residual liver weight to body weight was not significantly
      different. Steroid pretreatment disturbed LR in the S-PH group. On the other
      hand, low-dose steroid pretreatment improved LR and suppressed tumor necrosis
      factor (TNF)-alpha elevation in the S-PHA group, with recovery of STAT3 DNA
      binding activity. On the other hand, low-dose steroid pretreatment improved LR
      and suppressed TNF-alpha elevation in the S-PHA group, with recovery of STAT3 DNA
      binding activity. CONCLUSION: LR is disturbed after RF ablation, with high serum
      cytokine/chemokine induction. Low-dose steroid administration can improve LR
      after RF ablation with TNF-alpha suppression.

PMID- 22408350
TI  - S100A4 silencing blocks invasive ability of esophageal squamous cell carcinoma
      cells.
AB  - AIM: To investigate a potential role of S100A4 in esophagus squamous cell
      carcinoma metastasis (ESCCs). METHODS: Expression of S100A4 and E-cadherin were
      analyzed in frozen sections from ESCCs (metastasis, n = 28; non-metastasis, n =
      20) by reverse transcription-polymerase chain reaction, quantitative polymerase
      chain reaction and immunohistochemistry. To explore the influence of S100A4 on
      esophageal cancer invasion and metastasis, S100A4 was overexpressed or silenced
      by S100A4 siRNA in TE-13 or Eca-109 cells in vitro and in vivo. RESULTS: We found
      the mRNA and protein levels of S100A4 expression in ESCCs was significantly
      upregulated, and more importantly, that expression of S100A4 and E cadherin are
      strongly negatively correlated in patients who had metastasis. It was indicated
      that overexpression of S100A4 in TE-13 and Eca-109 cells downregulates the
      expression of E-cadherin, leading to increased cell migration in vitro, whereas
      knockdown of S100A4 inhibited cell migration and upregulation of E-cadherin
      expression. Moreover, the loss of cell metastatic potential was rescued by
      overexpression of E-cadherin completely. In addition, nude mice inoculated with
      S100A4 siRNA-transfected cells exhibited a significantly decreased invasion
      ability in vivo. CONCLUSION: S100A4 may be involved in ESCC progression by
      regulate E-cadherin expression, vector-based RNA interference targeting S100A4 is
      a potential therapeutic method for human ESCC.

PMID- 22408351
TI  - High-fat-induced intestinal permeability dysfunction associated with altered
      fecal bile acids.
AB  - AIM: To investigate whether high-fat-feeding is associated with increased
      intestinal permeability via alterations in bile acid metabolism. METHODS: Male
      C57Bl/6J mice were fed on a high-fat (n = 26) or low-fat diet (n = 24) for 15 wk.
      Intestinal permeability was measured from duodenum, jejunum, ileum and colon in
      an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal
      bile acids were analyzed with gas chromatography. Segments of jejunum and colon
      were analyzed for the expression of farnesoid X receptor (FXR) and tumor necrosis
      factor (TNF). RESULTS: Intestinal permeability was significantly increased by
      high-fat feeding in jejunum (median 0.334 for control vs 0.393 for high-fat, P =
      0.03) and colon (0.335 for control vs 0.433 for high-fat, P = 0.01), but not in
      duodenum or ileum. The concentration of nearly all identified bile acids was
      significantly increased by high-fat feeding (P < 0.001). The proportion of
      ursodeoxycholic acid (UDCA) in all bile acids was decreased (1.4% +/- 0.1% in
      high-fat vs 2.8% +/- 0.3% in controls, P < 0.01) and correlated inversely with
      intestinal permeability (r = -0.72, P = 0.01). High-fat feeding also increased
      jejunal FXR expression, as well as TNF expression along the intestine, especially
      in the colon. CONCLUSION: High-fat-feeding increased intestinal permeability,
      perhaps by a mechanism related to bile acid metabolism, namely a decreased
      proportion of fecal UDCA and increased FXR expression.

PMID- 22408352
TI  - Beneficial effect of sulphate-bicarbonate-calcium water on gallstone risk and
      weight control.
AB  - AIM: To investigate the effect of drinking sulphate-bicarbonate-calcium thermal
      water (TW) on risk factors for atherosclerosis and cholesterol gallstone disease.
      METHODS: Postmenopausal women with functional dyspepsia and/or constipation
      underwent a 12 d cycle of thermal (n = 20) or tap (n = 20) water controlled
      drinking. Gallbladder fasting volume at ultrasound, blood vitamin E, oxysterols
      (7-beta-hydroxycholesterol and 7-ketocholesterol), bile acid (BA), triglycerides,
      total/low density lipoprotein and high density lipoprotein cholesterol were
      measured at baseline and at the end of the study. Food consumption, stool
      frequency and body weight were recorded daily. RESULTS: Blood lipids, oxysterols
      and vitamin E were not affected by either thermal or tap water consumption.
      Fasting gallbladder volume was significantly (P < 0.005) smaller at the end of
      the study than at baseline in the TW (15.7 +/- 1.1 mL vs 20.1 +/- 1.7 mL) but not
      in the tap water group (19.0 +/- 1.4 mL vs 19.4 +/- 1.5 mL). Total serum BA
      concentration was significantly (P < 0.05) higher at the end of the study than at
      baseline in the TW (5.83 +/- 1.24 MUmol vs 4.25 +/- 1.00 MUmol) but not in the
      tap water group (3.41 +/- 0.46 MUmol vs 2.91 +/- 0.56 MUmol). The increased BA
      concentration after TW consumption was mainly accounted for by
      glycochenodeoxycholic acid. The number of pasta (P < 0.001), meat (P < 0.001) and
      vegetable (P < 0.005) portions consumed during the study and of bowel movements
      per day (P < 0.05) were significantly higher in the TW than in the tap water
      group. Body weight did not change at the end of the study as compared to baseline
      in both groups. CONCLUSION: Sulphate-bicarbonate-calcium water consumption has a
      positive effect on lithogenic risk and intestinal transit and allows maintenance
      of a stable body weight despite a high food intake.

PMID- 22408353
TI  - Duodenal stenting for malignant gastric outlet obstruction: prospective study.
AB  - AIM: To evaluate the results of duodenal stenting for palliation of
      gastroduodenal malignant obstruction by using a gastric outlet obstruction score
      (GOOS). METHODS: A prospective, non-randomized study was performed at a tertiary
      center between August 2005 and April 2010. Patients were eligible if they had
      malignant gastric outlet obstruction (GOO) and were not candidates for surgical
      treatment. Medical history and patient demographics were collected at baseline.
      Scheduled interviews were made on the day of the procedure and 15, 30, 90 and 180
      d later or unscheduled as necessary. RESULTS: Fifteen patients (6 male, 9 female;
      median age 61 years) with GOO who had undergone duodenal stenting were evaluated.
      Ten patients had metastasis at baseline (66.6%) and 14 were unable to accept oral
      intake (93.33%), including 7 patients who were using a feeding tube. Laboratory
      data showed biliary obstruction in eight cases (53.33%); all were submitted to
      biliary drainage. Two patients developed obstructive symptoms due to tumor
      ingrowth after 30 d and another due to tumor overgrowth after 180 d. Two cases of
      stent migration occurred. A good response to treatment was observed, with a mean
      time of approximately 1 d (19 h) until toleration of a liquid diet and slightly
      more than 2 d for both soft solids (51 h) and a solid food/normal diet (55 h).
      The mean time to first failure to maintain liquid intake (GOOS >= 1) was 93 d.
      During follow-up, the mean time to first failure to maintain the previously
      achieved GOOS of 2-3 (solid/semi-solid food), considered technical failure, was
      71 d. On the basis of oral intake a GOOS is defined: 0 for no oral intake; 1 for
      liquids only; 2 for soft solids only; 3 for low-residue or full diet. CONCLUSION:
      Enteral stenting to alleviate gastroduodenal malignant obstruction improves
      quality of life in patients with limited life expectancy, which can be evaluated
      by using a GOO scoring system.

PMID- 22408354
TI  - Original single-incision laparoscopic cholecystectomy for acute inflammation of
      the gallbladder.
AB  - AIM: To investigate the safety and feasibility of our original single-incision
      laparoscopic cholecystectomy (SILC) for acute inflamed gallbladder (AIG).
      METHODS: One hundred and ten consecutive patients underwent original SILC for
      gallbladder disease without any selection criteria and 15 and 11 of these were
      diagnosed with acute cholecystitis and acute gallstone cholangitis, respectively.
      A retrospective review was performed not only between SILC for AIG and non-AIG,
      but also between SILC for AIG and traditional laparoscopic cholecystectomy (TLC)
      for AIG in the same period. RESULTS: Comparison between SILC for AIG and non-AIG
      revealed that the operative time was longer in SILC for AIG (97.5 min vs 85.0
      min, P = 0.03). The open conversion rate (2/26 vs 2/84, P = 0.24) and
      complication rate (1/26 vs 3/84, P = 1.00) showed no differences, but a need for
      additional trocars was more frequent in SILC for AIG (5/24 vs 3/82, P = 0.01).
      Comparison between SILC for AIG and TLC for AIG revealed no differences based on
      statistical analysis. CONCLUSION: Our original SILC technique was adequately safe
      and feasible for the treatment of acute cholecystitis and acute gallstone
      cholangitis.

PMID- 22408355
TI  - Biliary reflux detection in anomalous union of the pancreatico-biliary duct
      patients.
AB  - AIM: To demonstrate the imaging findings of biliopancreatic and pancreatico
      biliary reflux in patients with anomalous union of the pancreatico-biliary duct
      (AUPBD) on gadoxetic acid-enhanced functional magnetic resonance cholangiography
      (fMRC). METHODS: This study included six consecutive patients (two men and four
      women; mean age 47.5 years) with AUPBD. All subjects underwent endoscopic
      retrograde cholangiopancreatography (ERCP); one subject also underwent bile
      sampling of the common bile duct (CBD) to measure the amylase level because his
      gadoxetic acid-enhanced fMRC images showed evidence of pancreatico-biliary reflux
      of pancreatic secretions. Of the five patients with choledochal cysts, four
      underwent pylorus-preserving pancreaticoduodenectomy. RESULTS: The five cases of
      choledochal cysts were classified as Todani classification I. In three of the six
      patients with AUPBD, injected contrast media reached the distal CBD and
      pancreatic duct on delay images, suggesting biliopancreatic reflux. In two of
      these six patients, a band-like filling defect was noted in the CBD on pre-fatty
      meal images, which decreased in size on delayed post-fatty meal images,
      suggesting pancreatico-biliary reflux of pancreatic secretions, and the bile
      sampled from the CBD in one patient had an amylase level of 113,000 IU/L. In one
      of the six patients with AUPBD, contrast media did not reach the distal CBD due
      to multiple CBD stones. CONCLUSION: Gadoxetic acid-enhanced fMRC successfully
      demonstrated biliopancreatic reflux of bile and pancreatico-biliary reflux of
      pancreatic secretions in patients with AUPBD with and without choledochal cysts.

PMID- 22408356
TI  - Synergistic effect of multiple predisposing risk factors on the development of
      bezoars.
AB  - AIM: To describe the clinical characteristics of patients with gastric or
      intestinal bezoars recently treated in our hospital. METHODS: In this study, a
      retrospective chart review of consecutive patients with gastrointestinal bezoars,
      who were treated at the Samsun Education and Research Hospital between January
      2006 and March 2011, was conducted. Data on demographic characteristics, clinical
      presentation, history of risk factors, diagnostic procedures, localization of
      bezoars, treatment interventions, and postoperative morbidity and mortality rates
      were collected and evaluated. RESULTS: Forty-two patients [26 (61.9%) males and
      16 (31.1%) females] with a mean +/- SD (range) age of 55.8 +/- 10.5 (37-74) years
      were enrolled in this study. Thirty-six patients (85.7%) had one or more
      predisposing risk factors for gastrointestinal bezoars. The most common
      predisposing risk factor was a history of previous gastric surgery which was
      identified in 18 patients (42.8%). Twenty three patients (54.8%) had multiple
      predisposing risk factors. Phytobezoars were identified in all patients except
      one who had a trichobezoar in the stomach. Non-operative endoscopic fragmentation
      was performed either initially or after unsuccessful medical treatment in 14
      patients with gastric bezoars and was completely successful in 10 patients
      (71.5%). Surgery was the most frequent treatment method in our study, which was
      required in 28 patients (66.7%). Intestinal obstruction secondary to bezoars was
      the most common complication (n = 18, 42.8%) in our study. CONCLUSION: The
      presence of multiple predisposing factors may create a synergistic effect in the
      development of bezoars.

PMID- 22408357
TI  - Genetic characteristics and pathogenicity of human hepatitis E virus in Nanjing,
      China.
AB  - AIM: To investigate the genetic characteristics and pathogenicity of hepatitis E
      virus (HEV) and assess the potential risk factors for sporadic hepatitis E.
      METHODS: Sixty-two serum samples from the patients with acute hepatitis E were
      collected, including 23 cases coinfected with hepatitis B virus. Anti-HEV
      detection and partial HEV RNA amplification were performed by enzyme immunoassays
      and reverse transcription-nested polymerase chain reaction (RT-nPCR) method,
      respectively, and PCR products were sequenced. The isolated human HEV sequences
      were analyzed phylogenetically. RESULTS: The positive rate of serum HEV RNA were
      21.0% (13/62), including 5 cases of liver failure. All the 13 isolates shared a
      82.1%-98.0% nucleotide homology with each other and had identities of 74.7%
      81.0%, 75.3%-78.6%, 75.3%-80.0% and 82.1%-96.1% with the corresponding regions of
      HEV genotypes 1-4, respectively. The human HEV strain GS-NJ-12 shared a 100%
      nucleotide identity with the swine HEV strain swIM6-43 isolated from Inner
      Mongolia, China. CONCLUSION: Swine may be a principal risk factor for occurrence
      of sporadic hepatitis E in eastern China, and genotype 4 HEV can induce acute
      liver failure.

PMID- 22408358
TI  - B7-H1 expression is associated with expansion of regulatory T cells in colorectal
      carcinoma.
AB  - AIM: To investigate the expression of B7-H1 in human colorectal carcinoma (CRC)
      to define its regulating effects on T cells in tumor microenvironment. METHODS:
      One hundred and two paraffin blocks and 33 fresh samples of CRC tissues were
      subject to this study. Immunohistochemistry was performed for B7-H1 and CD3
      staining in CRC tissues. Ficoll-Hypaque density gradient centrifugation was used
      to isolate peripheral blood mononuclear cells of fresh CRC tissues; flow
      cytometry and immunofluorescence staining were used for detection of regulatory T
      cells. Data was analyzed with statistical software. RESULTS: Costimulatory
      molecule B7-H1 was found strongly expressed in CRC tissues, localized in tumor
      cell membrane and cytoplasm, while weak or none expression of B7-H1 was detected
      in pared normal colorectal tissues. Meanwhile, CD3 positive T cells were found
      congregated in CRC tumor nest and stroma. Statistic analysis showed that B7-H1
      expression level was negatively correlated to the total T cell density in tumor
      nest (P < 0.0001) and tumor stroma (P = 0.0200) of 102 cases of CRC tissues.
      Among the total T cells, a variable amount of regulatory T cells with a clear
      Foxp3+ (forkhead box P3) staining could be detected in CRC tissues and patients'
      blood. Interestingly, in the 33 samples (15 cases of B7-H1(high) CRC tissues and
      18 cases of B7-H1(low) CRC tissues) of freshly isolated mononuclear cells from
      CRC tissues, the percentages of CD4+Foxp3+ and CD8+Foxp3+ regulatory T cells were
      found remarkably higher in B7-H1(high) CRC tissues than in B7-H1(low) CRC tissues
      (P = 0.0024, P = 0.0182), indicating that B7-H1 expression was involved in
      proliferation of regulatory T cell. No significant difference was found in CRC
      peripheral blood (P = 0.0863, P = 0.0678). PD-1 is the specific ligand for B7-H1
      pathway transferring inhibitory signal to T cell, which is expressed by activated
      T cell. Our further analysis of PD-1 expression on T cells in CRC tissues showed
      that conventional T cells (CD4+Foxp3-/CD8+Foxp3-), which was thought to
      contribute to the anti-tumor immune response, highly expressed PD-1; while
      regulatory T cells (CD4+Foxp3+/CD8+Foxp3-) almost failed to express PD-1. The
      average percentage of PD-1 expression on regulatory T cells was significantly
      higher than the percentage of PD-1 on conventional T cells (CD4+Foxp3- T cell, P
      < 0.0001; CD8+Foxp3- T cell, P < 0.0001). The diverse expression of PD-1 might
      lead to different fate of T cell subsets in B7-H1 over-expression CRC tumor
      microenvironment. CONCLUSION: B7-H1 expression in tumor cells can inhibit the
      conventional T cell proliferation in tumor microenvironment through the PD-1
      expression on conventional T cells.

PMID- 22408359
TI  - Interleukin-8 associates with adhesion, migration, invasion and chemosensitivity
      of human gastric cancer cells.
AB  - AIM: To investigate the relationship between Interleukin-8 (IL-8) and
      proliferation, adhesion, migration, invasion and chemosensitivity of gastric
      cancer (GC) cells. METHODS: The IL-8 cDNA was stably transfected into human GC
      cell line MKN-45 and selected IL-8-secreting transfectants. The expression of IL
      8 in human GC cell line KATO-III was inhibited by RNA interference. The
      expressions of mRNA and protein of IL-8 in GC cells were detected by real-time
      reverse transcription-polymerase chain reaction or enzyme-linked immunosorbent
      assay (ELISA). RESULTS: The overexpression of IL-8 resulted in an increased cell
      adhesion, migration and invasion, and a significant resistance to oxaliplatin in
      MKN-45 cells. Inhibition of IL-8 expression with small interfering RNA decreased
      the adhesion, migration and invasion functions and oxaliplatin resistance in KATO
      III cells. IL-8 increased NF-kappaB and Akt activities and adhesion molecules
      ICAM-1, VCAM-1, and CD44 expression in GC cells. CONCLUSION: Overexpression of IL
      8 promotes the adhesion, migration, invasion, and chemoresistance of GC cells,
      indicating that IL-8 is an important therapeutic target in GC.

PMID- 22408360
TI  - Serological and molecular study of hepatitis E virus among illegal blood donors.
AB  - AIM: To investigate the seroprevalence and molecular characteristics of hepatitis
      E virus (HEV) in the illegal blood donors (IBDs) of central China in the early
      1990s. METHODS: A total of 546 blood samples were collected from the IBDs in
      Maanshan city, a questionnaire was completed by each subject, detailing the age,
      sex, and periods of blood or plasma donation. Anhui Province and tested for the
      anti-HEV antibodies. The seropositive samples were subjected to nested reverse
      transcription-polymerase chain reaction and sequencing to analyze HEV partial
      genome. RESULTS: The prevalence of IgG and IgM HEV antibody in IBDs was 22.7% and
      1.8%, and genotype 4 was the dominant circulating HEV type in IBDs. The
      prevalence of anti-HEV IgG was significantly related to sex (OR = 4.905, P =
      0.004) and increased with age (OR = 2.78, P = 0.022), which ranged from 13.0% in
      those < 40 years old to 30.6% among older persons aged > 60 years. Moreover,
      frequency of blood donation was significantly associated with HEV seropositivity
      (OR = 2.06, P = 0.006). HEV partial sequences of ORF2 and obtained 3 sequences in
      serum samples of 10 IBDs which developed HEV specific IgM. CONCLUSION: This study
      helps define one of the possible routes of transmission of sporadic HEV infection
      and provides guidance to screen HEV in the blood donors so as to guarantee safe
      blood banks in China.

PMID- 22408361
TI  - Prophylaxis of chronic kidney disease after liver transplantation--experience
      from west China.
AB  - AIM: To evaluate the prophylaxis of chronic kidney disease (CKD) after liver
      transplantation (LT) with low-dose calcineurin inhibitor (CNI) and mycophenolate
      mofetil (MMF). METHODS: From March 1999 to December 2009, a total of 572 patients
      (478 males and 94 females) underwent LT enrolled in the study. Initial
      immunosuppression was by triple-drug regimens that included a CNI, MMF, and
      prednisone. The initial dose of CNI was 0.05-0.10 mg/kg per day for tacrolimus
      (TAC) and 5-10 mg/kg per d for cyclosporine A (CSA) respectively, and was
      gradually reduced based on a stable graft function. The serum trough level of CNI
      was 6-8 ng/mL for TAC and 120-150 ng/mL for CSA 3-mo post-operation, 4-6 ng/mL
      for TAC and 80-120 ng/mL for CSA 1-year after transplantation was expected with
      stable liver function. MMF was personalized between 1.0-1.5 g/d. Glomerular
      filtration rate (GFR) was estimated by an abbreviated Modification of Diet in
      Renal Disease formula. Risk factors of CKD were examined by univariate and
      multivariate logistic regression. RESULTS: With a definition of GFR < 60 mL/min
      per 1.73 m(2), the incidence of CKD was 17.3% 5-year after LT. There were 68.3%
      (293 of 429 cases) patients managed to control their TAC trough concentrations
      within 8 ng/mL and 58.0% (83 of 143 cases) patients' CSA trough concentrations
      within 150 ng/mL. Of the 450 recipients followed-up over 1 year, 55.5% (183 of
      330 cases) of which were treated with TAC had a trough concentration <= 6 ng/mL
      while 65.8% (79 of 120 cases) of which were treated with CSA had a concentration
      <= 120 ng/mL. The incidence of CKD in the groups of lower CNI trough
      concentrations was significantly lower than the groups with CNI concentrations
      above the ideal range. Patients with CKD had much higher CNI trough
      concentrations than that of patients without CKD. MMF was adopted in 359 patients
      (62.8%). Patients administrated with MMF had a relatively low CNI trough
      concentrations but with no significant difference. The graft function remained
      stable during follow-up. No difference was found between different groups of CNI
      trough concentrations. Pre-LT renal dysfunction, ages, acute kidney injury, high
      blood trough concentrations of CNI in 3 mo (TAC > 8 ng/mL, CSA > 150 ng/mL) and
      hypertension after operation were associated with CKD progression, while male
      gender and adoption of MMF were protection factors. CONCLUSION: Low dose of CNI
      combined with MMF managed to prevent CKD after LT with stable graft function.

PMID- 22408362
TI  - Transient small bowel angioedema due to intravenous iodinated contrast media.
AB  - Three cases of transient proximal small bowel angioedema induced by intravenous
      administration of nonionic iodinated contrast media (CM) are presented. Computed
      tomography (CT) images in the venous phase displayed the proximal small bowel
      with circumferential thickening of the wall including the duodenum and proximal
      segment of the jejunum. The bowel wall was normal in non-enhanced images, and
      normal or inconspicuous in arterial phase enhanced images. In one of the three
      cases, the bowel wall was thickened in venous phase but disappeared in the 40 s
      delayed phase images. No filling defect was seen in the lumen of the superior
      mesenteric artery and vein. No peritoneal effusion or mesentery abnormality was
      found. Each of these patients reported only mild abdominal discomfort and
      recovered without specific treatment within a short time. Only one patient
      suffered mild diarrhea after scanning which had resolved by the following day.
      The transient anaphylactic small bowel angioedema due to intravenous iodinated
      contrast media was easily diagnosed based on its characteristic CT findings and
      clinical symptoms. Differential diagnosis may include inflammatory and ischemic
      bowel disease, as well as neoplasms. A three-phase CT protocol and good
      understanding of this disorder are fundamentally important in the diagnosis of
      this condition. The supposed etiology behind the transient anaphylactic reaction
      to intravenous administration of iodinated CM in small bowel is similar to other
      CM-induced hypersensitive immediate reactions. The predilection location of
      transient anaphylactic bowel angioedema is the small intestine, particularly the
      proximal segment. A speculated cause may be the richer supply of vessels in the
      small intestine, ample mucous folds and loose connective tissue in the duodenum
      and the jejunum.

PMID- 22408363
TI  - Social-Emotional Learning Profiles of Preschoolers' Early School Success: A
      Person-Centered Approach.
AB  - Examined how aspects of social-emotional learning (SEL)-specifically, emotion
      knowledge, emotional and social behaviors, social problem-solving, and self
      regulation-clustered to typify groups of children who differ in terms of their
      motivation to learn, participation in the classroom, and other indices of early
      school adjustment and academic success. 275 four-year-old children from private
      day schools and Head Start were directly assessed and observed in these areas,
      and preschool and kindergarten teachers provided information on social and
      academic aspects of their school success. Three groups of children were
      identified: SEL Risk, SEL Competent-Social/Expressive, and SEL Competent
      Restrained. Group members differed on demographic dimensions of gender and center
      type, and groups differed in meaningful ways on school success indices, pointing
      to needed prevention/intervention programming. In particular, the SEL Risk group
      could benefit from emotion-focused programming, and the long-term developmental
      trajectory of the SEL Competent-Restrained group requires study.

PMID- 22408364
TI  - Exploring the Link between Caregiver Affect and Adolescent Sexual Behavior: Does
      Neighborhood Disadvantage Matter?
AB  - In a sample of urban youth (N = 1,070), we examined the links between primary
      caregiver affect (i.e., warmth and hostility) and two measures of sexual behavior
      in adolescence - early sexual initiation and sex with multiple partners. We also
      examined the extent to which neighborhood disadvantage moderated associations
      between caregiver affect and adolescent sexual behavior. We found that caregiver
      hostility was positively associated with early sex and sex with multiple partners
      in neighborhoods characterized by high levels of disadvantage, but inversely
      associated with both sex outcomes in neighborhoods characterized by low levels of
      disadvantage. Caregiver warmth, on the other hand, was inversely associated with
      early sexual initiation and sex with multiple partners in all neighborhoods
      regardless of neighborhood disadvantage.

PMID- 22408365
TI  - Poisson Growth Mixture Modeling of Intensive Longitudinal Data: An Application to
      Smoking Cessation Behavior.
AB  - Intensive longitudinal data (ILD) have become increasingly common in the social
      and behavioral sciences; count variables, such as the number of daily smoked
      cigarettes, are frequently-used outcomes in many ILD studies. We demonstrate a
      generalized extension of growth mixture modeling (GMM) to Poisson-distributed ILD
      for identifying qualitatively distinct trajectories in the context of
      developmental heterogeneity in count data. Accounting for the Poisson outcome
      distribution is essential for correct model identification and estimation. In
      addition, setting up the model in a way that is conducive to ILD measures helps
      with data complexities - large data volume, missing observations, and differences
      in sampling frequency across individuals. We present technical details of model
      fitting, summarize an empirical example of patterns of smoking behavior change,
      and describe research questions the generalized GMM helps to address.

PMID- 22408366
TI  - Using the Spinal Cord Injury Common Data Elements.
AB  - International Spinal Cord Injury (SCI) Data Sets include core, basic, and
      extended data sets. To date, 13 data sets have been published on the Web site of
      the International Spinal Cord Injury Society (ISCoS; www.iscos.org.uk), and
      several more are forthcoming. The data sets are constituted of data elements,
      which may be appropriate to use in trials conducted to test novel therapeutic
      candidates including neuroprotective drugs, various cell types, and
      rehabilitative strategies and devices. The National Institute of Neurological
      Disorders and Stroke (NINDS), the National Institutes of Health (NIH), embarked
      on a Common Data Element (CDE) Project 5 years ago. The mission of the NINDS CDE
      Project is to develop data standards for clinical research. The NINDS CDE team
      has since developed variable names and database structures for the International
      SCI Data Sets (ie, the SCI CDEs;
      http://www.commondataelements.ninds.nih.gov/SCI.aspx). Dataset variable names and
      database structure are exemplified with the International SCI Core Data Set and
      the International SCI Cardiovascular Function Basic Data Set. The consistency of
      the data sets and the CDE format may improve the ability to transfer critical
      medical information electronically from one center to another. The goals of the
      SCI CDE initiative are to increase the efficiency and effectiveness of clinical
      research studies and clinical treatment, increase data quality, facilitate data
      sharing, and help educate new clinical investigators. Pilot testing the SCI CDEs
      is an important step to ensure the SCI CDE effort achieves its goals.

PMID- 22408367
TI  - Quinolinic Acid, an endogenous molecule combining excitotoxicity, oxidative
      stress and other toxic mechanisms.
AB  - Quinolinic acid (QUIN), an endogenous metabolite of the kynurenine pathway, is
      involved in several neurological disorders, including Huntington's disease,
      Alzheimer's disease, schizophrenia, HIV associated dementia (HAD) etc. QUIN
      toxicity involves several mechanisms which trigger various metabolic pathways and
      transcription factors. The primary mechanism exerted by this excitotoxin in the
      central nervous system (CNS) has been largely related with the overactivation of
      N-methyl-D-aspartate receptors and increased cytosolic Ca(2+) concentrations,
      followed by mitochondrial dysfunction, cytochrome c release, ATP exhaustion, free
      radical formation and oxidative damage. As a result, this toxic pattern is
      responsible for selective loss of middle size striatal spiny GABAergic neurons
      and motor alterations in lesioned animals. This toxin has recently gained
      attention in biomedical research as, in addition to its proven excitotoxic
      profile, a considerable amount of evidence suggests that oxidative stress and
      energetic disturbances are major constituents of its toxic pattern in the CNS.
      Hence, this profile has changed our perception of how QUIN-related disorders
      combine different toxic mechanisms resulting in brain damage. This review will
      focus on the description and integration of recent evidence supporting old and
      suggesting new mechanisms to explain QUIN toxicity.

PMID- 22408368
TI  - Vertebrate hepatic lipase genes and proteins: a review supported by bioinformatic
      studies.
AB  - Hepatic lipase (gene: LIPC; enzyme: HL; E.C.3.1.1.3) is one of three members of
      the triglyceride lipase family that contributes to vascular lipoprotein
      degradation and serves a dual role in triglyceride hydrolysis and in facilitating
      receptor-mediated lipoprotein uptake into the liver. Amino acid sequences,
      protein structures, and gene locations for vertebrate LIPC (or Lipc for mouse and
      rat) genes and proteins were sourced from previous reports and vertebrate genome
      databases. Lipc was distinct from other neutral lipase genes (Lipg encoding
      endothelial lipase and Lpl encoding lipoprotein lipase [LPL]) and was located on
      mouse chromosome 9 with nine coding exons on the negative strand. Exon 9 of human
      LIPC and mouse and rat Lipc genes contained "stop codons" in different positions,
      causing changes in C-termini length. Vertebrate HL protein subunits shared 58%
      97% sequence identities, including active, signal peptide, disulfide bond, and N
      glycosylation sites, as well as proprotein convertase ("hinge") and heparin
      binding regions. Predicted secondary and tertiary structures revealed
      similarities with the three-dimensional structure reported for horse and human
      pancreatic lipases. Potential sites for regulating LIPC gene expression included
      CpG islands near the 5"-untranslated regions of the mouse and rat LIPC genes.
      Phylogenetic analyses examined the relationships and potential evolutionary
      origins of the vertebrate LIPC gene family with other neutral triglyceride lipase
      gene families (LIPG and LPL). We conclude that the triglyceride lipase ancestral
      gene for vertebrate neutral lipase genes (LIPC, LIPG, and LPL) predated the
      appearance of fish during vertebrate evolution.

PMID- 22408369
TI  - Fibromyalgia syndrome and spa therapy: myth or reality?
AB  - Fibromyalgia syndrome (FS) is a common musculoskeletal disorder characterized by
      otherwise unexplained chronic widespread pain, a lowered pain threshold, high
      tender point counts, sleep disturbances, fatigue, headache, irritable bowel
      syndrome, morning stiffness, paraesthesias in the extremities, often
      psychological distress and depressed mood. Consequently, FS has a negative impact
      on working capacity, family life, social functioning and quality of life. Because
      of unknown etiology and not clearly understood pathogenesis, there is no standard
      therapy regime for FS. A variety of medical treatments, including
      antidepressants, opioids, analgesic or non-steroidal anti-inflammatory drugs,
      sedatives, muscle relaxants and antiepileptics, have been used to treat FS.
      Currently, no pharmacological treatment for FS is consistently successful.
      According to recent guidelines, the optimal treatment of FS requires a
      multidisciplinary approach with a combination of non-pharmacological and
      pharmacological treatment modalities. Spa therapy is a popular treatment for FS
      in many European countries, as well as in Japan and Israel. However, despite
      their long history and popularity spa treatments are still the subject of debate
      and their role in modern medicine is still not clear. The objective of this
      review is to summarize the currently available information on clinical effects
      and mechanism of action of spa therapy in FS. We also provide some suggestions
      for further development in this area.

PMID- 22408370
TI  - A different way of coronary lesion preparation: stentablation and rotastenting.
AB  - Calcified coronary lesions are challenging to deal with, as they require optimal
      lesion preparation. Direct stenting in this scenario is associated with risk of
      stent-underexpansion, which is related to in-stent restenosis, target lesion
      revascularization and stent-thrombosis. We report on the interventional
      management of an underexpanded bare-metal stent not amenable to high-pressure
      balloon dilation and cutting-balloon. By using rotablation we could abrade the
      underexpanded stent struts and the calcification with subsequent implantation of
      a drug-eluting stent. Follow-up of 6 months revealed good results without
      evidence of significant restenosis. Our clinical experience and case reports in
      the literature suggest that this strategy might be an option for underexpanded
      stents not amenable to conventional techniques.

PMID- 22408372
TI  - Chorea as a first manifestation in young patients with systemic lupus
      erythematosus who was initially diagnosed with rheumatic Fever.
AB  - Chorea is a rare manifestation of systemic lupus erythematosus (SLE). We report
      on a young patient with chorea who was diagnosed initially with rheumatic fever.
      Follow up and further evaluation confirmed the diagnosis of SLE and anti
      phospholipid syndrome. Of special interest were the negative antiphospholipid
      (aPL) antibodies and the initial diagnosis of rheumatic fever which is still not
      uncommon problem in our region. The rarity of such presentation with joint and
      non specific increase of antistreptolysin O (ASO) titer might be the factors that
      led to an incorrect diagnosis. Early diagnosis and treatment of SLE and anti
      phospholipid syndrome are very crucial and should be considered with such
      presentation.

PMID- 22408371
TI  - Stroke Prevention in Atrial Fibrillation: Where are We Now?
AB  - Atrial fibrillation is the commonest arrhythmia worldwide and is a growing
      problem. AF is responsible for 25% of all strokes, and these patients suffer
      greater mortality and disability. Warfarin has traditionally been the only
      successful therapy for stroke prevention, but its limitations have resulted in
      underutilisation. Major progress has been made in AF research, leading to
      improved management strategies. Better risk stratification permits identification
      of truly low-risk patients who do not require anticoagulation and we are able to
      simplify ourevaluation of a patient's bleeding risk.The advent of novel
      anticoagulants means warfarin is no longer the only choice for stroke
      prophylaxis. These drugs circumvent many of warfarin's inconveniences, but
      onlylong-term study and use will conclusively demonstrate how they compare to
      warfarin. The landscape of stroke prevention in AF has changed with effective
      alternatives to warfarin available for the first time in 60 years-but each new
      option brings new considerations.

PMID- 22408373
TI  - Therapeutic options for the treatment of hypertension in children and
      adolescents.
AB  - Primary hypertension in children is increasing in prevalence with many cases
      likely going undiagnosed. The prevalence is currently estimated at between 3%-5%
      in the United States and may be higher in certain ethnic groups. Primary
      hypertension, once felt to be rare in children, is now considered to be about
      five times more common than secondary hypertension. This review provides
      information to guide physicians through an organized approach to: 1) screening
      children and adolescents for hypertension during routine visits; 2) using
      normative percentile data for diagnosis and classification; 3) performing a
      clinical evaluation to identify the presence of co-morbidities; 4) initiating a
      plan of care including subsequent follow-up blood pressure measurements,
      therapeutic lifestyle changes and pharmacologic therapies.

PMID- 22408375
TI  - Malignant ovarian tumors with induced expression of carbonyl reductase show
      spontaneous regression.
AB  - BACKGROUND: The present study investigated tumor proliferation in a tumor model
      using murine ovarian cancer cells with increased carbonyl reductase (CR)
      expression. METHODS: CR cDNA was transfected into murine T-Ag-MOSE ovarian cancer
      cells by lipofection. CR-transfected cells (CR induction group) or empty vector
      treated cells (control group) were injected into the backs of 8-week-old nude
      mice at a concentration of 0.5 * 10(6) per 0.2 mL. Subsequent tumor proliferation
      in both groups was observed for 5 weeks. RESULTS: The control group showed an
      increase in tumor volume during the 5 weeks of observation. However, tumor volume
      in the CR induction group increased up to the second week but then decreased
      continuously until the fifth week of observation. The tumor growth curves for the
      two groups showed a significant difference (Mann-Whitney U test, P < 0.001).
      Histological and biochemical experiments were performed using tumor tissues
      isolated in the third week. Necrosis and inflammatory cell infiltration were
      noted for tumors in the CR induction group. Also, the number of apoptotic cells
      was significantly increased in the CR induction group compared with the control
      group (P < 0.001). Milk fat globule EGF factor 8, an "eat-me" signal for
      phagocytes such as macrophages, was expressed extensively in the tumor cytoplasm
      and interstitial cells of the CR induction group, and engulfment of apoptotic
      cells by macrophages was observed. Vascular endothelial growth factor expression
      in tumors was notably decreased in the CR induction group compared with the
      control group. CONCLUSION: Increased necrosis due to engulfing of apoptotic cells
      by phagocytes attracted by increased milk fat globule EGF factor 8 was considered
      to be the mechanism of spontaneous tumor regression in the CR induction group.

PMID- 22408374
TI  - Clinical efficacy of vorinostat in a patient with leiomyosarcoma.
AB  - Leiomyosarcoma is a heterogeneous tumor group, representing <1% of all new
      cancers diagnosed in United States. Treatment choice is based upon site, grade,
      and extent of disease. However, prognosis for metastatic or unresectable sarcoma
      is very poor with reported median survival of 12 months. Response to chemotherapy
      has been approximately 8% to 39% based upon the chemotherapeutic agent and
      whether used alone or in combination. Vorinostat is an orally active, potent, and
      competitive inhibitor of histone deacetylases approved for cutaneous T-cell
      lymphoma. There are limited preclinical data illustrating the activity of histone
      deacetylase inhibitors in sarcoma. Here is a case of a lady with leiomyosarcoma
      who has progressed through multiple chemotherapeutic agent who has achieved a
      partial response to vorinostat treatment.

PMID- 22408376
TI  - Long-term treatment of metastatic colorectal cancer with panitumumab.
AB  - Colorectal cancer is one of the leading causes of cancer-related deaths
      worldwide. More than 30% patients present with metastases at diagnoses and will
      require systemic chemotherapy. In recent years many anti-EGFR targets have been
      developed. Among them, panitumumab, a fully human IgG2 monoclonal antibody has
      shown important benefits in the treatment of this disease.

PMID- 22408377
TI  - Kikuchi's Disease: A Rare Cause of Fever and Lymphadenopathy.
AB  - Kikuchi's disease is a benign condition that occurs in women. A young woman
      presented to the hospital with fevers and cervical lymphadenopathy. Infectious
      work-up was negative except for streptococcus pharyngitis. Imaging studies
      revealed the presence of diffuse cervical and axillary lymphadenopathy. The
      fevers persisted and she underwent excisional cervical lymph node biopsy that
      revealed histiocytic necrotizing lymphadenitis corresponding to a benign
      diagnosis of Kikuchi's disease. Three months later, the patient was afebrile and
      there was complete resolution of the cervical lymphadenopathy.

PMID- 22408378
TI  - Three new species of Fancy Case caterpillars from threatened forests of Hawaii
      (Lepidoptera, Cosmopterigidae, Hyposmocoma).
AB  - The endemic Hawaiian moth genus Hyposmocoma includes 348 described species and
      perhaps twice as many that remain undescribed. The genus is unusual within
      Lepidoptera in that its larvae create distinctive silk cases in which they
      perambulate while protected and camouflaged. An extraordinary diversity of case
      types exists, and to date more than ten different types have been identified,
      each corresponding roughly to a separate evolutionary lineage. In this study, we
      describe three new species of Hyposmocoma: Hyposmocoma ipohapuusp. n. from Big
      Island, Hyposmocoma makawaosp. n. from Makawao Forest Reserve in Mauiand
      Hyposmocoma tantalasp. n. from Mt. Tantalus, Oahu, all of which produce tubular
      purse cases during their larval stage. We also describe the female of Hyposmocoma
      inversella Walsingham, which was previously undescribed, and re-describe two
      closely related species, Hyposmocoma auropurpurea Walsingham and Hyposmocoma
      nebulifera Walsingham, neither which have been formally described in recent
      years. We present for the first time, primer sequences for a 705 bp fragment of
      CAD, designed for Hyposmocoma and relatives. The molecular phylogeny based on
      mitochondrial and nuclear loci demonstrates that all are distinct species. The
      discovery of a new, endemic species from Mt. Tantalus, an area with many invasive
      species, suggests that even relatively degraded areas in Hawaii would be worthy
      of active conservation efforts.

PMID- 22408379
TI  - A new species of genus Syntactus Forster (Hymenoptera, Ichneumonidae,
      Ctenopelmatinae) with a key to Oriental and Eastern Palearctic species.
AB  - A new species, Syntactus jiulianicus Sun & Sheng, sp.n. belonging to the tribe
      Pionini of the subfamily Ctenopelmatinae (Hymenoptera, Ichneumonidae), collected
      from Jiangxi Province, China, is reported. Illustrations of the new species and
      Syntactus delusor (Linnaeus, 1758), Syntactus minor (Holmgren, 1857) and
      Syntactus varius (Holmgren, 1858) are provided. A key to the species of Syntactus
      known from the Oriental and Eastern Palaearctic Regions is given.

PMID- 22408380
TI  - Antispila oinophylla new species (Lepidoptera, Heliozelidae), a new North
      American grapevine leafminer invading Italian vineyards: taxonomy, DNA barcodes
      and life cycle.
AB  - A grapevine leafminer Antispila oinophylla van Nieukerken & Wagner, sp. n., is
      described both from eastern North America (type locality: Georgia) and as a new
      important invader in North Italian vineyards (Trentino and Veneto Region) since
      2006. The species is closely related to, and previously confused with Antispila
      ampelopsifoliella Chambers, 1874, a species feeding on Virginia creeper
      Parthenocissus quinquefolia (L.) Planchon., and both are placed in an informal
      Antispila ampelopsifoliella group. Wing pattern, genitalia, and DNA barcode data
      all confirm the conspecificity of native North American populations and Italian
      populations. COI barcodes differ by only 0-1.23%, indicating that the Italian
      populations are recently established from eastern North America. The new species
      feeds on various wild Vitis species in North America, on cultivated Vitis
      vinifera L. in Italy, and also on Parthenocissus quinquefolia in Italy. North
      American Antispila feeding on Parthenocissus include at least two other species,
      one of which is Antispila ampelopsifoliella. Morphology and biology of the new
      species are contrasted with those of North American Antispila Hubner, 1825
      species and European Holocacista rivillei (Stainton, 1855). The source population
      of the introduction is unknown, but cases with larvae or pupae, attached to
      imported plants, are a likely possibility. DNA barcodes of the three European
      grapevine leafminers and those of all examined Heliozelidae are highly
      diagnostic. North American Vitaceae-feeding Antispila form two species complexes
      and include several as yet unnamed taxa. The identity of three out of the four
      previously described North American Vitaceae-feeding species cannot be
      unequivocally determined without further revision, but these are held to be
      different from Antispila oinophylla. In Italy the biology of Antispila oinophylla
      was studied in a vineyard in the Trento Province (Trentino-Alto Adige Region) in
      2008 and 2009. Mature larvae overwinter inside their cases, fixed to vine trunks
      or training stakes. The first generation flies in June. An additional generation
      occurs from mid-August onwards. The impact of the pest in this vineyard was
      significant with more than 90% of leaves infested in mid-summer. Since the
      initial discovery in 2006, the pest spread to several additional Italian
      provinces, in 2010 the incidence of infestation was locally high in commercial
      vineyards. Preliminary phylogenetic analyses suggest that Antispila is
      paraphyletic, and that the Antispila ampelopsifoliella group is related to
      Coptodisca Walsingham, 1895, Holocacista Walsingham & Durrant, 1909 and
      Antispilina Hering, 1941, all of which possess reduced wing venation. Vitaceae
      may be the ancestral hostplant family for modern Heliozelidae.

PMID- 22408381
TI  - Predicting patch occupancy in fragmented landscapes at the rangewide scale for an
      endangered species: an example of an American warbler.
AB  - AIM: Our objective was to identify the distribution of the endangered golden
      cheeked warbler (Setophaga chrysoparia) in fragmented oak-juniper woodlands by
      applying a geoadditive semiparametric occupancy model to better assist decision
      makers in identifying suitable habitat across the species breeding range on which
      conservation or mitigation activities can be focused and thus prioritize
      management and conservation planning.  LOCATION: Texas, USA.  METHODS: We used
      repeated double-observer detection/non-detection surveys of randomly selected (n
      = 287) patches of potential habitat to evaluate warbler patch-scale presence
      across the species breeding range. We used a geoadditive semiparametric occupancy
      model with remotely sensed habitat metrics (patch size and landscape composition)
      to predict patch-scale occupancy of golden-cheeked warblers in the fragmented oak
      juniper woodlands of central Texas, USA.  RESULTS: Our spatially explicit model
      indicated that golden-cheeked warbler patch occupancy declined from south to
      north within the breeding range concomitant with reductions in the availability
      of large habitat patches. We found that 59% of woodland patches, primarily in the
      northern and central portions of the warbler's range, were predicted to have
      occupancy probabilities <=0.10 with only 3% of patches predicted to have
      occupancy probabilities >0.90. Our model exhibited high prediction accuracy (area
      under curve = 0.91) when validated using independently collected warbler
      occurrence data.  MAIN CONCLUSIONS: We have identified a distinct spatial
      occurrence gradient for golden-cheeked warblers as well as a relationship between
      two measurable landscape characteristics. Because habitat-occupancy relationships
      were key drivers of our model, our results can be used to identify potential
      areas where conservation actions supporting habitat mitigation can occur and
      identify areas where conservation of future potential habitat is possible.
      Additionally, our results can be used to focus resources on maintenance and
      creation of patches that are more likely to harbour viable local warbler
      populations.

PMID- 22408382
TI  - Diversity arrays technology (DArT) markers in apple for genetic linkage maps.
AB  - Diversity Arrays Technology (DArT) provides a high-throughput whole-genome
      genotyping platform for the detection and scoring of hundreds of polymorphic loci
      without any need for prior sequence information. The work presented here details
      the development and performance of a DArT genotyping array for apple. This is the
      first paper on DArT in horticultural trees. Genetic mapping of DArT markers in
      two mapping populations and their integration with other marker types showed that
      DArT is a powerful high-throughput method for obtaining accurate and reproducible
      marker data, despite the low cost per data point. This method appears to be
      suitable for aligning the genetic maps of different segregating populations. The
      standard complexity reduction method, based on the methylation-sensitive PstI
      restriction enzyme, resulted in a high frequency of markers, although there was
      52-54% redundancy due to the repeated sampling of highly similar sequences.
      Sequencing of the marker clones showed that they are significantly enriched for
      low-copy, genic regions. The genome coverage using the standard method was 55
      76%. For improved genome coverage, an alternative complexity reduction method was
      examined, which resulted in less redundancy and additional segregating markers.
      The DArT markers proved to be of high quality and were very suitable for genetic
      mapping at low cost for the apple, providing moderate genome coverage. ELECTRONIC
      SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11032
      011-9579-5) contains supplementary material, which is available to authorized
      users.

PMID- 22408383
TI  - Genomic organisation of the Mal d 1 gene cluster on linkage group 16 in apple.
AB  - European populations exhibit progressive sensitisation to food allergens, and
      apples are one of the foods for which sensitisation is observed most frequently.
      Apple cultivars vary greatly in their allergenic characteristics, and a better
      understanding of the genetic basis of low allergenicity may therefore allow
      allergic individuals to increase their fruit intake. Mal d 1 is considered to be
      a major apple allergen, and this protein is encoded by the most complex allergen
      gene family. Not all Mal d 1 members are likely to be involved in allergenicity.
      Therefore, additional knowledge about the existence and characteristics of the
      different Mal d 1 genes is required. In the present study, we investigated the
      genomic organisation of the Mal d 1 gene cluster in linkage group 16 of apple
      through the sequencing of two bacterial artificial chromosome clones. The results
      provided new information on the composition of this family with respect to the
      number and orientation of functional and pseudogenes and their physical
      distances. The results were compared with the apple and peach genome sequences
      that have recently been made available. A broad analysis of the whole apple
      genome revealed the presence of new genes in this family, and a complete list of
      the observed Mal d 1 genes is supplied. Thus, this study provides an important
      contribution towards a better understanding of the genetics of the Mal d 1 family
      and establishes the basis for further research on allelic diversity among
      cultivars in relation to variation in allergenicity. ELECTRONIC SUPPLEMENTARY
      MATERIAL: The online version of this article (doi:10.1007/s11032-011-9588-4)
      contains supplementary material, which is available to authorized users.

PMID- 22408384
TI  - Induced point mutations in the phytoene synthase 1 gene cause differences in
      carotenoid content during tomato fruit ripening.
AB  - In tomato, carotenoids are important with regard to major breeding traits such as
      fruit colour and human health. The enzyme phytoene synthase (PSY1) directs
      metabolic flux towards carotenoid synthesis. Through TILLING (Targeting Induced
      Local Lesions IN Genomes), we have identified two point mutations in the Psy1
      gene. The first mutation is a knockout allele (W180*) and the second mutation
      leads to an amino acid substitution (P192L). Plants carrying the Psy1 knockout
      allele show fruit with a yellow flesh colour similar to the r, r mutant, with no
      further change in colour during ripening. In the line with P192L substitution,
      fruit remain yellow until 3 days post-breaker and eventually turn red. Metabolite
      profiling verified the absence of carotenoids in the W180* line and thereby
      confirms that PSY1 is the only enzyme introducing substrate into the carotenoid
      pathway in ripening fruit. More subtle effects on carotenoid accumulation were
      observed in the P192L line with a delay in lycopene and beta-carotene
      accumulation clearly linked to a very slow synthesis of phytoene. The observation
      of lutein degradation with ripening in both lines showed that lutein and its
      precursors are still synthesised in ripening fruit. Gene expression analysis of
      key genes involved in carotenoid biosynthesis revealed that expression levels of
      genes in the pathway are not feedback-regulated by low levels or absence of
      carotenoid compounds. Furthermore, protein secondary structure modelling
      indicated that the P192L mutation affects PSY1 activity through misfolding,
      leading to the low phytoene accumulation.

PMID- 22408385
TI  - Does reflection lead to wise choices?
AB  - Does conscious reflection lead to good decision-making? Whereas engaging in
      reflection is traditionally thought to be the best way to make wise choices,
      recent psychological evidence undermines the role of reflection in lay and expert
      judgement. The literature suggests that thinking about reasons does not improve
      the choices people make, and that experts do not engage in reflection, but base
      their judgements on intuition, often shaped by extensive previous experience. Can
      we square the traditional accounts of wisdom with the results of these empirical
      studies? Should we even attempt to? I shall defend the view that philosophy and
      cognitive sciences genuinely interact in tackling questions such as whether
      reflection leads to making wise choices.

PMID- 22408386
TI  - Mass spectrometry-based carboxyl footprinting of proteins: method evaluation.
AB  - Protein structure determines function in biology, and a variety of approaches
      have been employed to obtain structural information about proteins. Mass
      spectrometry-based protein footprinting is one fast-growing approach. One
      labeling-based footprinting approach is the use of a water-soluble carbodiimide,
      1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and glycine ethyl ester (GEE)
      to modify solvent-accessible carboxyl groups on glutamate (E) and aspartate (D).
      This paper describes method development of carboxyl-group modification in protein
      footprinting. The modification protocol was evaluated by using the protein
      calmodulin as a model. Because carboxyl-group modification is a slow reaction
      relative to protein folding and unfolding, there is an issue that modifications
      at certain sites may induce protein unfolding and lead to additional modification
      at sites that are not solvent-accessible in the wild-type protein. We
      investigated this possibility by using hydrogen deuterium amide exchange (H/DX).
      The study demonstrated that application of carboxyl group modification in probing
      conformational changes in calmodulin induced by Ca(2+) binding provides useful
      information that is not compromised by modification-induced protein unfolding.

PMID- 22408387
TI  - Characterization of Transferrin Glycopeptide Structures in Human Cerebrospinal
      Fluid.
AB  - Transferrin in cerebrospinal fluid (CSF) exists as a mixture of silao and asialo
      glycoforms believed to originate from liver and brain respectively. We have
      previously shown that alteration in the asialo glycoform pattern could be an
      indication of certain anomalies in the central nervous system. Additionally, CSF
      asialo-transferrin has been shown to be a reliable marker to assess cerebrospinal
      leakage in head trauma. Therefore, the CSF transferrin glycoform pattern could be
      a useful diagnostic and prognostic tool. In this study we sought to characterize,
      in-depth, the transferrin glycovariants in cerebrospinal fluid using a
      combination of two-dimensional gel electrophoresis and high precision mass
      spectrometry analysis. Cerebrospinal fluid transferrin was detected as multiple
      spots (seven major spots) with different isoelectric points and slight shift in
      apparent molecular mass. High resolution (>60,000) and high accuracy (< 3 ppm
      error) mass spectrometry analysis revealed that each spot had a unique
      glycopeptide signature. MS(n) analysis enabled characterization of the glycan
      structure directly from the in-gel digested spots. The multiple spots detected
      for cerebrospinal fluid transferrin were mainly due to heterogeneity of di
      antennary and tri-antennary glycans harboring a varying number of terminal N
      acetylneuraminic acids and the existence of a high mannose and high N
      acetylhexosamine glycosylated species.

PMID- 22408388
TI  - Atmospheric Pressure Chemical Ionization Tandem Mass Spectrometry of Carotenoids.
AB  - Carotenoids are natural pigments synthesized by plants and photosynthetic
      microorganisms, some of which, like beta-carotene, are precursors of vitamin A,
      and others such as lutein and lycopene might function in the prevention of age
      related macular degeneration and prostate cancer, respectively. Mass spectrometry
      provides high sensitivity and selectivity for the identification and quantitative
      analysis of carotenoids in biological samples, and previous studies have
      described how atmospheric pressure chemical ionization (APCI) offers distinct
      advantages over electrospray and fast atom bombardment for the analysis of
      specific carotenoids. Since APCI product ion tandem mass spectra have been
      reported for only a few carotenoids, a detailed investigation of twelve carotenes
      and xanthophylls was carried out using both positive ion and negative ion APCI
      tandem mass spectrometry with collision-induced dissociation. Using protonated
      molecules as precursor ions in positive ion mode and radical anions in negative
      ion mode, characteristic fragment ions were identified that may be used to
      distinguish between carotenoids.

PMID- 22408389
TI  - Dissociation Behavior of Tryptic and Intramolecular Disulfide-linked Peptide Ions
      Modified in the Gas Phase via Ion/Ion Reactions.
AB  - Protonated tryptic peptides, somatostatin-14, and oxytocin have been subjected to
      reactions with doubly deprotonated 4-formyl-1,3-benzenedisulfonic acid (FBDSA) in
      the gas phase. The major product is a negatively-charged complex comprised of the
      peptide and the reagent. Upon dehydration of the complex, all peptides show
      evidence for Schiff base formation involving a primary amine of the peptide. Some
      peptides also show evidence for the formation of a relatively strong
      electrostatic interaction without Schiff base formation (i.e., a mixture of
      isomeric precursor ions is generated upon dehydration of the complex). Ion trap
      collision-induced dissociation of the dehydration products from all peptides
      examined gave distinct product ion spectra relative to the deprotonated and
      protonated forms of the peptides. The distinct behavior of the modified ions is
      attributed to the highly stable charge carrying sulfonate group, which tends to
      inhibit intramolecular proton transfer in negatively charged species. Modified
      anions of the peptides with an intramolecular disulfide linkage show evidence for
      cleavage of both the disulfide linkage and an amide bond in the loop defined by
      the disulfide bond. Modification of protonated peptides via charge inversion with
      FBDSA is a useful means for generating novel and distinct ion-types that can
      provide complementary structural information upon subsequent activation to that
      obtained from dissociation of protonated or deprotonated forms of the peptide.

PMID- 22408390
TI  - Chemical reaction of soybean flavonoids with DNA: a computational study using the
      implicit solvent model.
AB  - Genistein, daidzein, glycitein and quercetin are flavonoids present in soybean
      and other vegetables in high amounts. These flavonoids can be metabolically
      converted to more active forms, which may react with guanine in the DNA to form
      complexes and can lead to DNA depurination. We assumed two ultimate carcinogen
      forms of each of these flavonoids, diol epoxide form and diketone form. Density
      functional theory (DFT) and Hartree-Fock (HF) methods were used to study the
      reaction thermodynamics between active forms of flavonoids and DNA guanine.
      Solvent reaction field method of Tomasi and co-workers and the Langevin dipoles
      method of Florian and Warshel were used to calculate the hydration free energies.
      Activation free energy for each reaction was estimated using the linear free
      energy relation. Our calculations show that diol epoxide forms of flavonoids are
      more reactive than the corresponding diketone forms and are hence more likely
      flavonoid ultimate carcinogens. Genistein, daidzein and glycitein show comparable
      reactivity while quercetin is less reactive toward DNA.

PMID- 22408391
TI  - Imidazolines as non-classical bioisosteres of N-acyl homoserine lactones and
      quorum sensing inhibitors.
AB  - A series of selected 2-substituted imidazolines were synthesized in moderate to
      excellent yields by a modification of protocols reported in the literature. They
      were evaluated as potential non-classical bioisosteres of AHL with the aim of
      counteracting bacterial pathogenicity. Imidazolines 18a, 18e and 18f at various
      concentrations reduced the violacein production by Chromobacterium violaceum,
      suggesting an anti-quorum sensing profile against Gram-negative bacteria.
      Imidazoline 18b did not affect the production of violacein, but had a
      bacteriostatic effect at 100 MUM and a bactericidal effect at 1 mM. Imidazoline
      18a bearing a hexyl phenoxy moiety was the most active compound of the series,
      rendering a 72% inhibitory effect of quorum sensing at 100 MUM. Imidazoline 18f
      bearing a phenyl nonamide substituent presented an inhibitory effect on quorum
      sensing at a very low concentration (1 nM), with a reduction percentage of 28%.
      This compound showed an irregular performance, decreasing inhibition at
      concentrations higher than 10 MUM, until reaching 100 MUM, at which concentration
      it increased the inhibitory effect with a 49% reduction percentage. When
      evaluated on Serratia marcescens, compound 18f inhibited the production of
      prodigiosin by 40% at 100 MUM.

PMID- 22408392
TI  - Expression analysis of MYC genes from Tamarix hispida in response to different
      abiotic stresses.
AB  - The MYC genes are a group of transcription factors containing both bHLH and ZIP
      motifs that play important roles in the regulation of abscisic acid (ABA)
      responsive genes. In the present study, to investigate the roles of MYC genes
      under NaCl, osmotic and ABA stress conditions, nine MYC genes were cloned from
      Tamarix hispida. Real-time reverse-transcriptase (RT)-PCR showed that all nine
      MYC genes were expressed in root, stem and leaf tissues, but that the levels of
      the transcripts of these genes in the various tissues differed notably. The MYC
      genes were highly induced in the roots in response to ABA, NaCl and osmotic
      stresses after 3 h; however, in the stem and leaf tissues, MYC genes were highly
      induced only when exposed to these stresses for 6 h. In addition, most of these
      MYC genes were highly expressed in roots in comparison with stems and leaves.
      Furthermore, the MYC genes were more highly induced in roots than in stem and
      leaf tissues, indicating that these genes may play roles in stress responses
      mainly in the roots rather than the stems and leaves. The results of this present
      study suggest that MYCs are involved in salt and osmotic stress tolerances and
      are controlled by the ABA signal transduction pathway.

PMID- 22408393
TI  - Serine hydroxymethyltransferase from the cold adapted microorganism Psychromonas
      ingrahamii: a low temperature active enzyme with broad substrate specificity.
AB  - Serine hydroxymethyltransferase from the psychrophilic microorganism Psychromonas
      ingrahamii was expressed in Escherichia coli and purified as a His-tag fusion
      protein. The enzyme was characterized with respect to its spectroscopic,
      catalytic, and thermodynamic properties. The properties of the psychrophilic
      enzyme have been contrasted with the characteristics of the homologous
      counterpart from E. coli, which has been structurally and functionally
      characterized in depth and with which it shares 75% sequence identity.
      Spectroscopic measures confirmed that the psychrophilic enzyme displays
      structural properties almost identical to those of the mesophilic counterpart. At
      variance, the P. ingrahamii enzyme showed decreased thermostability and high
      specific activity at low temperature, both of which are typical features of cold
      adapted enzymes. Furthermore, it was a more efficient biocatalyst compared to E.
      coli serine hydroxymethyltransferase (SHMT) particularly for side reactions. Many
      beta-hydroxy-alpha-amino acids are SHMT substrates and represent important
      compounds in the synthesis of pharmaceuticals, agrochemicals and food additives.
      Thanks to these attractive properties, this enzyme could have a significant
      potential for biotechnological applications.

PMID- 22408394
TI  - Effect of fiber esterification on fundamental properties of oil palm empty fruit
      bunch fiber/poly(butylene adipate-co-terephthalate) biocomposites.
AB  - A new class of biocomposites based on oil palm empty fruit bunch fiber and
      poly(butylene adipate-co-terephthalate) (PBAT), which is a biodegradable
      aliphatic aromatic co-polyester, were prepared using melt blending technique. The
      composites were prepared at various fiber contents of 10, 20, 30, 40 and 50 wt%
      and characterized. Chemical treatment of oil palm empty fruit bunch (EFB) fiber
      was successfully done by grafting succinic anhydride (SAH) onto the EFB fiber
      surface, and the modified fibers were obtained in two levels of grafting (low and
      high weight percentage gain, WPG) after 5 and 6 h of grafting. The FTIR
      characterization showed evidence of successful fiber esterification. The results
      showed that 40 wt% of fiber loading improved the tensile properties of the
      biocomposite. The effects of EFB fiber chemical treatments and various organic
      initiators content on mechanical and thermal properties and water absorption of
      PBAT/EFB 60/40 wt% biocomposites were also examined. The SAH-g-EFB fiber at low
      WPG in presence of 1 wt% of dicumyl peroxide (DCP) initiator was found to
      significantly enhance the tensile and flexural properties as well as water
      resistance of biocomposite (up to 24%) compared with those of untreated fiber
      reinforced composites. The thermal behavior of the composites was evaluated from
      thermogravimetric analysis (TGA)/differential thermogravimetric (DTG)
      thermograms. It was observed that, the chemical treatment has marginally improved
      the biocomposites' thermal stability in presence of 1 wt% of dicumyl peroxide at
      the low WPG level of grafting. The improved fiber-matrix surface enhancement in
      the chemically treated biocomposite was confirmed by SEM analysis of the tensile
      fractured specimens.

PMID- 22408396
TI  - Compositional variation in sugars and organic acids at different maturity stages
      in selected small fruits from pakistan.
AB  - Selected soluble sugars and organic acids were analyzed in strawberry, sweet
      cherry, and mulberry fruits at different ripening stages by HPLC. The amounts of
      fructose, glucose and sucrose were found to be: strawberry (1.79-2.86, 1.79-2.25
      and 0.01-0.25 g/100 g FW), sweet cherry (0.76-2.35, 0.22-3.39 and 0.03-0.13 g/100
      g) and mulberry (3.07-9.41, 1.53-4.95 and 0.01-0.25 g/100 g) at un-ripened to
      fully-ripened stages, respectively. The strawberry, sweet cherry and mulberry
      mainly contained tartaric, citric and ascorbic acids in the range of 16-55, 70
      1934 and 11-132 mg/100 g; 2-8, 2-10 and 10-17 mg/100 g; 2-118, 139-987 and 2-305
      mg/100 g at un-ripened to fully-ripened stages, respectively. Fructose and
      glucose were established to be the major sugars in all the tested fruit while
      citric and ascorbic acid were the predominant organic acids in strawberry and
      mulberry while tartaric acid was mainly present in sweet cherry. The tested
      fruits mostly showed an increase in the concentration of sugars and organic acids
      with ripening.

PMID- 22408395
TI  - MetastamiRs: non-coding MicroRNAs driving cancer invasion and metastasis.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides that function as
      negative regulators of gene expression by either inhibiting translation or
      inducing deadenylation-dependent degradation of target transcripts. Notably,
      deregulation of miRNAs expression is associated with the initiation and
      progression of human cancers where they act as oncogenes or tumor suppressors
      contributing to tumorigenesis. Abnormal miRNA expression may provide potential
      diagnostic and prognostic tumor biomarkers and new therapeutic targets in cancer.
      Recently, several miRNAs have been shown to initiate invasion and metastasis by
      targeting multiple proteins that are major players in these cellular events, thus
      they have been denominated as metastamiRs. Here, we present a review of the
      current knowledge of miRNAs in cancer with a special focus on metastamiRs. In
      addition we discuss their potential use as novel specific markers for cancer
      progression.

PMID- 22408397
TI  - Acute oral toxicity evaluations of some zinc(II) complexes derived from 1-(2
      salicylaldiminoethyl)piperazine Schiff bases in rats.
AB  - The current study described the synthesis and the in vivo acute oral toxicity
      evaluations in Sprague Dawley rats. The compounds were characterized by elemental
      analyses, LC-MS, FTIR, (1)H NMR, (13)C NMR and UV-visible spectroscopy. In the
      acute toxicity study, a single administration of the compounds was performed
      orally to the rats at the single doses of 2000 mg/kg and they were then monitored
      for possible side effects, mortality or behavioral changes up to 14 days. The
      serum level of aspartate (AST), alanine aminotransferases (ALT), alkaline
      phosphate (ALP), triglyceride, high density lipoprotein (HDL), immunoglobulins
      (GAM) and the C-reactive proteins did not significantly change. The hematological
      indices white blood cells (WBC), haematocrit (HCT), red blood cells (RBC), mean
      corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC), and
      mean corpuscular hemoglobin (MCH) were within the normal range. The renal
      function indices examined were also within the reference range. Generally, the
      compounds exhibited low toxic effects as required for further in vivo therapeutic
      studies.

PMID- 22408398
TI  - Phylogeographical analysis on Squalidus argentatus recapitulates historical
      landscapes and drainage evolution on the island of Taiwan and mainland China.
AB  - Phylogeographical analyses on Squalidus argentatus samples from thirteen
      localities within mainland China and Taiwan were conducted for biogeographic
      studies, as their dispersal strictly depends on geological evolution of the
      landmasses. A total of 95 haplotypes were genotyped for mtDNA cyt b gene in 160
      specimens from nine river systems. Relatively high levels of haplotype diversity
      (h = 0.984) and low levels of nucleotide diversity (pi = 0.020) were detected in
      S. argentatus. Two major phylogenetic haplotype groups, A and B, were revealed
      via phylogenetic analysis. The degree of intergroup divergence (3.96%) indicates
      that these groups diverged about 4.55 myr (million years) ago. Haplotype network
      and population analyses indicated significant genetic structure (F(ST) = 0.775),
      largely concordant with the geographical location of the populations. According
      to SAMOVA analysis, we divided these populations into four units: Yangtze-Pearl,
      Qiantang-Minjiang, Jiulong-Beijiang and Taiwan groups. Mismatch distribution
      analysis, neutrality tests and Bayesian skyline plots indicated a significant
      population expansion for lineage A and B, approximately dated 0.35 and 0.04 myr
      ago, respectively. We found strong geographical organization of the haplotype
      clades across different geographic scales that can be explained by episodes of
      dispersal and population expansion followed by population fragmentation and
      restricted gene flow.

PMID- 22408400
TI  - Isolation and characterization of 21 microsatellite loci in Cardiocrinum
      giganteum var. yunnanense (Liliaceae), an important economic plant in China.
AB  - Twenty-one microsatellite markers from the genome of Cardiocrinum giganteum var.
      yunnanense, an important economic plant in China, were developed with a fast
      isolation protocol by amplified fragment length polymorphism of sequences
      containing repeats (FIASCO). Polymorphism within each locus was assessed in 24
      wild individuals from Gaoligong Mountains in western Yunnan Province, China. The
      number of alleles per locus ranged from 2 to 4 with a mean of 2.9. The expected
      and observed levels of heterozygosity ranged from 0.042 to 0.726 and from 0.000
      to 1.000, with averages of 0.44 and 0.31, respectively. These polymorphic
      microsatellite markers should prove useful in population genetics studies and
      assessments of genetic variation to develop conservation and management
      strategies for this species.

PMID- 22408399
TI  - Chemical composition and in vitro antifungal activity screening of the Allium
      ursinum L. (Liliaceae).
AB  - The objective of the study was to summarize the methods for isolating and
      identifying natural sulfur compounds from Allium ursinum (ramson) and to discuss
      the active constituents with regard to antifungal action. Using chromatographic
      techniques, the active constituents were isolated and subsequently identified.
      Analyses by high-performance liquid chromatography (HPLC) suggested that these
      compounds were sulfur constituents, with a characteristic absorbance at 250 nm.
      Gas chromatography-mass spectrometry (GC-MS) analyses allowed the chemical
      structures of the isolated constituents to be postulated. We adopted the same
      methods to identify the health-giving profiling of ramsons and the effects are
      thought to be primarily derived from the presence and breakdown of the
      alk(en)ylcysteine sulphoxide, alliin and its subsequent breakdown to allicin
      (sulfur-compounds of ramson) in connection with antifungal action. The aim of the
      study was the characterization of the chemical composition of ramsons and the
      testing of the action of the in vitro extracts, on different strains of Candida
      albicans. The main goal was to highlight the most efficient extracts of Allium
      ursinum that can provide long-term antifungal activity without remissions. The
      extracts from Allium ursinum plants, inhibited growth of Candida spp. cells at
      concentrations ranging from 0.5 to 4.0 mg/mL, while that of adherent cells at
      concentrations ranging from 1.0 to > 4.0 mg/mL, depending on the yeast and plant
      species.

PMID- 22408401
TI  - Elevated peripheral blood plasma concentrations of tie-2 and angiopoietin 2 in
      patients with neuroendocrine tumors.
AB  - BACKGROUND: Gastro-entero-pancreatic/neuroendocrine (NET) tumors are highly
      vascularized neoplasms. However, our knowledge concerning circulating levels of
      the angiogenic factors in NET patients still remains insufficient. METHODS: The
      aim of this study was to measure plasma concentrations of VEGF, angiopoietin 1
      (Ang-1), angiopoietin 2 (Ang-2), soluble Tie-2, endostatin, osteopontin (OPN) and
      chromogranin A (CgA) in 36 NET patients and 16 controls. RESULTS: Only the plasma
      concentrations of Tie-2 and CgA were higher in NET patients as compared to
      controls. These levels were within the reference range in controls; however one
      control demonstrated slightly elevated Tie-2 and 4 elevated CgA. Similarly, in
      the subgroup of patients with carcinoid syndrome, only Tie-2 and CgA
      concentrations were higher than those in patients with non-functioning NETs. In
      turn, in the subgroup of metastatic patients, only Ang-2 levels were higher than
      in those with localized disease. A positive correlation was found between Ang-2
      and Tie-2 levels in metastatic patients and between Ang-1 and Tie-2 in localized
      NETs. CONCLUSIONS: The plasma concentration of Tie-2 is proposed as an additional
      marker for NET patients and seems to be similarly effective as the currently used
      CgA level. Moreover, higher plasma levels of Ang-2 together with the positive
      correlation between Ang-2 and Tie-2 levels in metastatic subjects, implies that
      cases with a Tie-2 level above the upper limits, together with higher level of
      Ang-2 seem to be highly predictive of metastases.

PMID- 22408402
TI  - Nanoscopic and photonic ultrastructural characterization of two distinct insulin
      amyloid states.
AB  - Two different conformational isoforms or amyloid strains of insulin with
      different cytotoxic capacity have been described previously. Herein these
      filamentous and fibrillar amyloid states of insulin were investigated using
      biophysical and spectroscopic techniques in combination with luminescent
      conjugated oligothiophenes (LCO). This new class of fluorescent probes has a well
      defined molecular structure with a distinct number of thiophene units that can
      adopt different dihedral angles depending on its binding site to an amyloid
      structure. Based on data from surface charge, hydrophobicity, fluorescence
      spectroscopy and imaging, along with atomic force microscopy (AFM), we deduce the
      ultrastructure and fluorescent properties of LCO stained insulin fibrils and
      filaments. Combined total internal reflection fluorescence microscopy (TIRFM) and
      AFM revealed rigid linear fibrous assemblies of fibrils whereas filaments showed
      a short curvilinear morphology which assemble into cloudy deposits. All studied
      LCOs bound to the filaments afforded more blue-shifted excitation and emission
      spectra in contrast to those corresponding to the fibril indicating a different
      LCO binding site, which was also supported by less efficient hydrophobic probe
      binding. Taken together, the multi-tool approach used here indicates the power of
      ultrastructure identification applying AFM together with LCO fluorescence
      interrogation, including TIRFM, to resolve structural differences between amyloid
      states.

PMID- 22408403
TI  - Pharmacological mechanisms underlying gastroprotective activities of the
      fractions obtained from Polygonum minus in Sprague Dawley rats.
AB  - The leaves of Polygonum minus were fractionated using an eluting solvent to
      evaluate the pharmacological mechanisms underlying the anti-ulcerogenic activity
      of P. minus. Different P. minus fractions were obtained and evaluated for their
      ulcer preventing capabilities using the ethanol induction method. In this study,
      Sprague Dawley rats weighing 150-200 g were used. Different parameters were
      estimated to identify the active fraction underlying the mechanism of the
      gastroprotective action of P. minus: the gastric mucus barrier, as well as
      superoxide dismutase, total hexosamine, and prostaglandin synthesis. Amongst the
      five fractions from the ethanolic extract of P. minus, the ethyl acetate:methanol
      1:1 v/v fraction (F2) significantly (p < 0.005) exhibited better inhibition of
      ulcer lesions in a dose-dependent manner. In addition, rats pre-treated with F2
      showed a significant elevation in superoxide dismutase (SOD), hexosamine and PGE2
      levels in the stomach wall mucosa in a dose-dependent matter. Based on these
      results, the ethyl acetate:methanol 1:1 v/v fraction was considered to be the
      best fraction for mucous protection in the ethanol induction model. The
      mechanisms underlying this protection were attributed to the synthesis of
      antioxidants and PGE2.

PMID- 22408404
TI  - Molecular diagnostic and pathogenesis of hereditary hemochromatosis.
AB  - Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized
      by enhanced intestinal absorption of dietary iron. Without therapeutic
      intervention, iron overload leads to multiple organ damage such as liver
      cirrhosis, cardiomyopathy, diabetes, arthritis, hypogonadism and skin
      pigmentation. Most HH patients carry HFE mutant genotypes: homozygosity for
      p.Cys282Tyr or p.Cys282Tyr/p.His63Asp compound heterozygosity. In addition to HFE
      gene, mutations in the genes that encode hemojuvelin (HJV), hepcidin (HAMP),
      transferrin receptor 2 (TFR2) and ferroportin (SLC40A1) have been associated with
      regulation of iron homeostasis and development of HH. The aim of this review was
      to identify the main gene mutations involved in the pathogenesis of type 1, 2, 3
      and 4 HH and their genetic testing indication. HFE testing for the two main
      mutations (p.Cys282Tyr and p.His63Asp) should be performed in all patients with
      primary iron overload and unexplained increased transferrin saturation and/or
      serum ferritin values. The evaluation of the HJV p.Gly320Val mutation must be the
      molecular test of choice in suspected patients with juvenile hemochromatosis with
      less than 30 years and cardiac or endocrine manifestations. In conclusion, HH is
      an example that genetic testing can, in addition to performing the differential
      diagnostic with secondary iron overload, lead to more adequate and faster
      treatment.

PMID- 22408405
TI  - Olmesartan attenuates the impairment of endothelial cells induced by oxidized low
      density lipoprotein through downregulating expression of LOX-1.
AB  - Oxidized low density lipoprotein (ox-LDL) and its receptor, lectin-Like ox-LDL
      receptor-1 (LOX-1), play important roles in the development of endothelial
      injuries. Olmesartan can protect endothelial cells from the impairment caused by
      various pathological stimulations. In the present study we investigated whether
      olmesartan decreased the impairment of endothelial cells induced by ox-LDL by
      exerting its effects on LOX-1 both in vitro and in vivo. Incubation of cultured
      endothelial cells of neonatal rats with ox-LDL for 24 h or infusion of ox-LDL in
      mice for 3 weeks led to the remarkable impairment of endothelial cells, including
      increased lactate dehydrogenase synthesis, phosphorylation of p38 mitogen
      activated protein kinases (p38 MAPK) and expression of apoptotic genes such as B
      cell leukemia/lymphoma 2 (Bcl-2)-associated X protein (Bax) and caspase-3.
      Simultaneously, the cell vitality and expression of Bcl-2 gene were greatly
      reduced. All these effects, however, were significantly suppressed by the
      treatment with olmesartan. Furthermore, ox-LDL promoted up-regulation of LOX-1
      expression either in cultured endothelial cells or in the aortas of mice, which
      was reversed with the administration of olmesartan. Our data indicated that
      olmesartan may attenuate the impairment of endothelial cell via down-regulation
      of the increased LOX-1 expression induced by ox-LDL.

PMID- 22408406
TI  - Dietary fibers and cardiometabolic diseases.
AB  - The high prevalence of cardiovascular disease (CVD) is largely attributable to
      the contemporary lifestyle that is often sedentary and includes a diet high in
      saturated fats and sugars and low ingestion of polyunsaturated fatty acids
      (PUFAs), fruit, vegetables, and fiber. Experimental data from both animals and
      humans suggest an association between increased dietary fiber (DF) intakes and
      improved plasma lipid profiles, including reduced low density lipoprotein
      cholesterol (LDL-C) concentrations. These observations underline that the intake
      of DF may protect against heart disease and stroke.

PMID- 22408408
TI  - Composition, structure and functional properties of protein concentrates and
      isolates produced from walnut (Juglans regia L.).
AB  - In this study, composition, structure and the functional properties of protein
      concentrate (WPC) and protein isolate (WPI) produced from defatted walnut flour
      (DFWF) were investigated. The results showed that the composition and structure
      of walnut protein concentrate (WPC) and walnut protein isolate (WPI) were
      significantly different. The molecular weight distribution of WPI was uniform and
      the protein composition of DFWF and WPC was complex with the protein aggregation.
      H(0) of WPC was significantly higher (p < 0.05) than those of DFWF and WPI,
      whilst WPI had a higher H(0) compared to DFWF. The secondary structure of WPI was
      similar to WPC. WPI showed big flaky plate like structures; whereas WPC appeared
      as a small flaky and more compact structure. The most functional properties of
      WPI were better than WPC. In comparing most functional properties of WPI and WPC
      with soybean protein concentrate and isolate, WPI and WPC showed higher fat
      absorption capacity (FAC). Emulsifying properties and foam properties of WPC and
      WPI in alkaline pH were comparable with that of soybean protein concentrate and
      isolate. Walnut protein concentrates and isolates can be considered as potential
      functional food ingredients.

PMID- 22408407
TI  - Risks of using antifouling biocides in aquaculture.
AB  - Biocides are chemical substances that can deter or kill the microorganisms
      responsible for biofouling. The rapid expansion of the aquaculture industry is
      having a significant impact on the marine ecosystems. As the industry expands, it
      requires the use of more drugs, disinfectants and antifoulant compounds
      (biocides) to eliminate the microorganisms in the aquaculture facilities. The use
      of biocides in the aquatic environment, however, has proved to be harmful as it
      has toxic effects on the marine environment. Organic booster biocides were
      recently introduced as alternatives to the organotin compounds found in
      antifouling products after restrictions were imposed on the use of tributyltin
      (TBT). The replacement products are generally based on copper metal oxides and
      organic biocides. The biocides that are most commonly used in antifouling paints
      include chlorothalonil, dichlofluanid, DCOIT (4,5-dichloro-2-n-octyl-4
      isothiazolin-3-one, Sea-nine 211((r))), Diuron, Irgarol 1051, TCMS pyridine
      (2,3,3,6-tetrachloro-4-methylsulfonyl pyridine), zinc pyrithione and Zineb. There
      are two types of risks associated with the use of biocides in aquaculture: (i)
      predators and humans may ingest the fish and shellfish that have accumulated in
      these contaminants and (ii) the development of antibiotic resistance in bacteria.
      This paper provides an overview of the effects of antifouling (AF) biocides on
      aquatic organisms. It also provides some insights into the effects and risks of
      these compounds on non-target organisms.

PMID- 22408409
TI  - Functional expression of an orchid fragrance gene in Lactococcus lactis.
AB  - Vanda Mimi Palmer (VMP), an orchid hybrid of Vanda tesselata and Vanda Tan Chay
      Yan is a highly scented tropical orchid which blooms all year round. Previous
      studies revealed that VMP produces a variety of isoprenoid volatiles during
      daylight. Isoprenoids are well known to contribute significantly to the scent of
      most fragrant plants. They are a large group of secondary metabolites which may
      possess valuable characteristics such as flavor, fragrance and toxicity and are
      produced via two pathways, the mevalonate (MVA) pathway or/and the 2-C-methyl-D
      erythritol-4-phosphate (MEP) pathway. In this study, a sesquiterpene synthase
      gene denoted VMPSTS, previously isolated from a floral cDNA library of VMP was
      cloned and expressed in Lactococcus lactis to characterize the functionality of
      the protein. L. lactis, a food grade bacterium which utilizes the mevalonate
      pathway for isoprenoid production was found to be a suitable host for the
      characterization of plant terpene synthases. Through recombinant expression of
      VMPSTS, it was revealed that VMPSTS produced multiple sesquiterpenes and
      germacrene D dominates its profile.

PMID- 22408410
TI  - Antinociceptive and anti-inflammatory effects of octacosanol from the leaves of
      Sabicea grisea var. grisea in mice.
AB  - Sabicea species are used in the Amazon for treatment of fever and malaria, which
      suggests that its chemical constituents may have some effect on pain and
      inflammation. Phytochemical analysis of the hexane fraction obtained from the
      crude ethanol extract from Sabicea grisea var. grisea Cham. & Schltdl
      (Rubiaceae), an endemic plant in Brazil, resulted in the isolation of
      octacosanol. This study investigated the antinociceptive and anti-inflammatory
      effects of the octacosanol in different experimental models. The crude ethanolic
      extract and hexane fraction obtained from the leaves of S. grisea produced an
      inhibition of acetic acid-induced pain. Moreover, octacosanol isolated from the
      hexane fraction produced a significant inhibition of pain response elicited by
      acetic acid. Pre-treatment with yohimbine, an alpha 2-adrenergic receptor
      antagonist, notably reversed the antinociceptive activity induced by octacosanol
      in the abdominal constriction test. Furthermore, mice treated with octacosanol
      did not exhibit any behavioral alteration during the hot plate and rota-rod
      tests, indicating non-participation of the supraspinal components in the
      modulation of pain by octacosanol with no motor abnormality. In the formalin
      test, octacosanol did not inhibit the licking time in first phase (neurogenic
      pain), but significantly inhibited the licking time in second phase (inflammatory
      pain) of mice. The anti-inflammatory effect of octacosanol was evaluated using
      carrageenan-induced pleurisy. The octacosanol significantly reduced the total
      leukocyte count and neutrophils influx, as well as TNF-alpha levels in the
      carrageenan-induced pleurisy. This study revealed that the mechanism responsible
      for the antinociceptive and anti-inflammatory effects of the octacosanol appears
      to be partly associated with an inhibition of alpha 2-adrenergic transmission and
      an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, these
      results demonstrated that the octacosanol from the leaves of S. grisea possesses
      antinociceptive and anti-inflammatory activities, which could be of relevance for
      the pharmacological control of pain and inflammatory processes.

PMID- 22408411
TI  - Tetrachloridocuprates(II)-synthesis and electron paramagnetic resonance (EPR)
      spectroscopy.
AB  - Ionic liquids (ILs) on the basis of metal containing anions and/or cations are of
      interest for a variety of technical applications e.g., synthesis of particles,
      magnetic or thermochromic materials. We present the synthesis and the results of
      electron paramagnetic resonance (EPR) spectroscopic analyses of a series of some
      new potential ionic liquids based on tetrachloridocuprates(II), [CuCl(4)](2-),
      with different sterically demanding cations: hexadecyltrimethylammonium 1,
      tetradecyltrimethylammonium 2, tetrabutylammonium 3 and benzyltriethylammonium 4.
      The cations in the new compounds were used to achieve a reasonable separation of
      the paramagnetic Cu(II) ions for EPR spectroscopy. The EPR hyperfine structure
      was not resolved. This is due to the exchange broadening, resulting from still
      incomplete separation of the paramagnetic Cu(II) centers. Nevertheless, the
      principal values of the electron Zeemann tensor (g(?) and g(?)) of the complexes
      could be determined. Even though the solid substances show slightly different
      colors, the UV/Vis spectra are nearly identical, indicating structural changes of
      the tetrachloridocuprate moieties between solid state and solution. The complexes
      have a promising potential e.g., as high temperature ionic liquids, as precursors
      for the formation of copper chloride particles or as catalytic paramagnetic ionic
      liquids.

PMID- 22408412
TI  - Acidic polysaccharide extracts from Gastrodia Rhizomes suppress the
      atherosclerosis risk index through inhibition of the serum cholesterol
      composition in Sprague Dawley rats fed a high-fat diet.
AB  - Obesity is associated with a broad spectrum of cardio-metabolic disturbances,
      including atherosclerosis and cardiovascular disease (CDV). A high-fat diet has
      been shown to cause an elevation of the plasma cholesterol levels in humans, and
      the control of serum cholesterol has been demonstrated to be important in the
      prevention of CVD and atherosclerosis. The aims of this study were to demonstrate
      that crude and acidic polysaccharide extracts from Gastrodia rhizomes suppress
      atherosclerosis through the regulation of serum lipids in Sprague Dawley (SD)
      rats fed a high-fat diet. We examined the concentrations of serum lipids,
      including total cholesterol, triglycerides, high-density lipoproteins (HDL)
      cholesterol, and low-density lipoproteins (LDL) cholesterol, in SD rats fed a
      high-fat diet and evaluated the atherogenic index. Here, we show that both crude
      and acidic polysaccharide extracts from Gastrodia rhizomes inhibited the total
      cholesterol and LDL levels. Moreover, there was a significantly suppressed
      atherosclerosis risk due to the acidic polysaccharide extract from Gastrodia
      rhizome. Taken together, our results suggested that acidic polysaccharide
      extracts from Gastrodia rhizomes might be beneficial for lowering the incidence
      of CVD and atherosclerosis by reducing the de novo synthesis of total cholesterol
      and the LDL levels.

PMID- 22408413
TI  - Analysis of Snail-1, E-cadherin and claudin-1 expression in colorectal adenomas
      and carcinomas.
AB  - We report the expression of Snail-1, E-cadherin and claudin-1 by indirect
      immunohistochemistry in colonic neoplasia. Snail-1 is a zinc finger transcription
      factor expressed in cells that already have undergone almost complete epithelial
      mesenchymal transition (EMT) and have already evaded from the tumor. The main
      mechanism by which Snail induces EMT is downregulation of E-cadherin, of which
      expression was shown to be frequently downregulated in many different types of
      tumors, where it accompanies the invasiveness and metastatic behavior of
      malignant cells. Moreover, Snail-1 may downregulate the expression of claudin-1,
      a cell-cell adhesion protein which plays a likely role in progression and
      dissemination during tumorigenesis. Snail-1 was expressed in both carcinoma and
      adenoma cells with histologically normal epithelium in the mucosa, adjacent to
      the tumors, without significant differences, and predominant strong intensity of
      staining. Statistically significant differences were revealed between normal and
      tumorous epithelium (p = 0.003) at the subcellular level, where the shift of the
      protein to the cytoplasm with combined cytoplasmic/nuclear or pure cytoplasmic
      expression was observed. E-cadherin expression was present in 100% of cases of
      both adenocarcinomas and adenomas, with prevailing strong membranous
      immunoreactivity and no differences between protein expression in tumors and
      normal mucosa. Predominating strong positivity of claudin-1 was detected in tumor
      cells of adenocarcinomas and adenomas. Marked differences were seen in protein
      localization, where membranous staining, typical for nontumorous epithelium,
      changed to combined membranous/cytoplasmic expression in adenocarcinomas (p =
      0.0001) and adenomas (0.0002), in which cytoplasmic shift was associated with a
      higher degree of dysplasia. Furthermore, membranous/cytoplasmic localization was
      more frequent in the carcinoma group (87%) in comparison with adenomas (51%) (p =
      0.0001). We conclude that dystopic subcellular localizations of Snail-1 and
      claudin-1 may participate in changes of cellular morphology and behavior which
      might be associated with altered effectory pathways of proteins and thus
      substantially contribute to the cancer development.

PMID- 22408414
TI  - Coenzyme Q metabolism is disturbed in high fat diet-induced non-alcoholic fatty
      liver disease in rats.
AB  - Oxidative stress is believed to be a major contributory factor in the development
      of non alcoholic fatty liver disease (NAFLD), the most common liver disorder
      worldwide. In this study, the effects of high fat diet-induced NAFLD on Coenzyme
      Q (CoQ) metabolism and plasma oxidative stress markers in rats were investigated.
      Rats were fed a standard low fat diet (control) or a high fat diet (57%
      metabolizable energy as fat) for 18 weeks. The concentrations of total (reduced +
      oxidized) CoQ9 were increased by >2 fold in the plasma of animals fed the high
      fat diet, while those of total CoQ10 were unchanged. Reduced CoQ levels were
      raised, but oxidized CoQ levels were not, thus the proportion in the reduced form
      was increased by about 75%. A higher percentage of plasma CoQ9 as compared to
      CoQ10 was in the reduced form in both control and high fat fed rats. Plasma
      protein thiol (SH) levels were decreased in the high fat-fed rats as compared to
      the control group, but concentrations of lipid hydroperoxides and low density
      lipoprotein (LDL) conjugated dienes were unchanged. These results indicate that
      high fat diet-induced NAFLD in rats is associated with altered CoQ metabolism and
      increased protein, but not lipid, oxidative stress.

PMID- 22408415
TI  - Preparation of TiO2 nanocrystallite powders coated with 9 mol% ZnO for cosmetic
      applications in sunscreens.
AB  - The preparation of TiO(2) nanocrystallite powders coated with and without 9 mol%
      ZnO has been studied for cosmetic applications in sunscreens by a co
      precipitation process using TiCl(4) and Zn(NO(3))(2).6H(2)O as starting
      materials. XRD results show that the phases of anatase TiO(2) and rutile TiO(2)
      coexist for precursor powders without added ZnO (T-0Z) and calcined at 523 to 973
      K for 2 h. When the T-0Z precursor powders are calcined at 1273 K for 2 h, only
      the rutile TiO(2) appears. In addition, when the TiO(2) precursor powders contain
      9 mol% ZnO (T-9Z) are calcined at 873 to 973 K for 2 h, the crystallized samples
      are composed of the major phase of rutile TiO(2) and the minor phases of anatase
      TiO(2) and Zn(2)Ti(3)O(8). The analyses of UV/VIS/NIR spectra reveal that the
      absorption of the T-9Z precursor powders after being calcined has a red-shift
      effect in the UV range with increasing calcination temperature. Therefore, the
      TiO(2) nanocrystallite powders coated with 9 mol% ZnO can be used as the
      attenuate agent in the UV-A region for cosmetic applications in sunscreens.

PMID- 22408416
TI  - Early exercise affects mitochondrial transcription factors expression after
      cerebral ischemia in rats.
AB  - Increasing evidence shows that exercise training is neuroprotective after stroke,
      but the underlying mechanisms are unknown. To clarify this critical issue, the
      current study investigated the effects of early treadmill exercise on the
      expression of mitochondrial biogenesis factors. Adult rats were subjected to
      ischemia induced by middle cerebral artery occlusion followed by reperfusion.
      Expression of two genes critical for transcriptional regulation of mitochondrial
      biogenesis, peroxisome proliferator-activated receptor coactivator-1 (PGC-1) and
      nuclear respiratory factor-1 (NRF-1), were examined by RT-PCR after five days of
      exercise starting at 24 h after ischemia. Mitochondrial protein cytochrome C
      oxidase subunit IV (COX IV) was detected by Western blot. Neurological status and
      cerebral infarct volume were evaluated as indices of brain damage. Treadmill
      training increased levels of PGC-1 and NRF-1 mRNA, indicating that exercise
      promotes rehabilitation after ischemia via regulation of mitochondrial
      biogenesis.

PMID- 22408417
TI  - Voltage gated ion channel function: gating, conduction, and the role of water and
      protons.
AB  - Ion channels, which are found in every biological cell, regulate the
      concentration of electrolytes, and are responsible for multiple biological
      functions, including in particular the propagation of nerve impulses. The
      channels with the latter function are gated (opened) by a voltage signal, which
      allows Na(+) into the cell and K(+) out. These channels have several positively
      charged amino acids on a transmembrane domain of their voltage sensor, and it is
      generally considered, based primarily on two lines of experimental evidence, that
      these charges move with respect to the membrane to open the channel. At least
      three forms of motion, with greatly differing extents and mechanisms of motion,
      have been proposed. There is a "gating current", a capacitative current preceding
      the channel opening, that corresponds to several charges (for one class of
      channel typically 12-13) crossing the membrane field, which may not require
      protein physically crossing a large fraction of the membrane. The coupling to the
      opening of the channel would in these models depend on the motion. The conduction
      itself is usually assumed to require the "gate" of the channel to be pulled apart
      to allow ions to enter as a section of the protein partially crosses the
      membrane, and a selectivity filter at the opposite end of the channel determines
      the ion which is allowed to pass through. We will here primarily consider K(+)
      channels, although Na(+) channels are similar. We propose that the mechanism of
      gating differs from that which is generally accepted, in that the positively
      charged residues need not move (there may be some motion, but not as gating
      current). Instead, protons may constitute the gating current, causing the gate to
      open; opening consists of only increasing the diameter at the gate from
      approximately 6 A to approximately 12 A. We propose in addition that the gate
      oscillates rather than simply opens, and the ion experiences a barrier to its
      motion across the channel that is tuned by the water present within the channel.
      Our own quantum calculations as well as numerous experiments of others are
      interpreted in terms of this hypothesis. It is also shown that the evidence that
      supports the motion of the sensor as the gating current can also be consistent
      with the hypothesis we present.

PMID- 22408418
TI  - Screening of crude plant extracts with anti-obesity activity.
AB  - Obesity is a global health problem. It is also known to be a risk factor for the
      development of metabolic disorders, type 2 diabetes, systemic hypertension,
      cardiovascular disease, dyslipidemia, and atherosclerosis. In this study, we
      screened crude extracts from 400 plants to test their anti-obesity activity using
      porcine pancreatic lipase assay (PPL; triacylglycerol lipase, EC 3.1.1.3) in
      vitro activity. Among the 400 plants species examined, 44 extracts from plants,
      showed high anti-lipase activity using 2,4-dinitrophenylbutyrate as a substrate
      in porcine pancreatic lipase assay. Furthermore, 44 plant extracts were
      investigated for their inhibition of lipid accumulation in 3T3-L1 cells. Among
      these 44 extracts examined, crude extracts from 4 natural plant species were
      active. Salicis Radicis Cortex had the highest fat inhibitory activity, whereas
      Rubi Fructus, Corni Fructus, and Geranium nepalense exhibited fat inhibitory
      capacity higher than 30% at 100 MUg/mL in 3T3-L1 adipocytes, suggesting anti
      obesity activity. These results suggest that four potent plant extracts might be
      of therapeutic interest with respect to the treatment of obesity.

PMID- 22408419
TI  - The effect of C-terminal helix on the stability of FF domain studied by molecular
      dynamics simulation.
AB  - To investigate the effect of C-terminal helix on the stability of the FF domain,
      we studied the native domain FF3-71 from human HYPA/FBP11 and the truncated
      version FF3-60 with C-terminal helix being deleted by molecular dynamics
      simulations with GROMACS package and GROMOS 43A1 force field. The results
      indicated that the structures of truncated version FF3-60 were evident different
      from those of native partner FF3-71. Compared with FF3-71, the FF3-60 lost some
      native contacts and exhibited some similar structural characters to those of
      intermediate state. The C-terminal helix played a major role in stabilizing the
      FF3-71 domain. To a certain degree, the FF domain had a tendency to form an
      intermediate state without the C-terminal helix. In our knowledge, this was the
      first study to examine the role of C-terminal helix of FF domain in detail by
      molecular dynamics simulations, which was useful to understand the three-state
      folding mechanism of the small FF domain.

PMID- 22408420
TI  - Characterization of catalase from psychrotolerant Psychrobacter piscatorii T-3
      exhibiting high catalase activity.
AB  - A psychrotolerant bacterium, strain T-3 (identified as Psychrobacter piscatorii),
      that exhibited an extraordinarily high catalase activity was isolated from the
      drain pool of a plant that uses H(2)O(2) as a bleaching agent. Its cell extract
      exhibited a catalase activity (19,700 U.mg protein(-1)) that was higher than that
      of Micrococcus luteus used for industrial catalase production. Catalase was
      approximately 10% of the total proteins in the cell extract of the strain. The
      catalase (PktA) was purified homogeneously by only two purification steps, anion
      exchange and hydrophobic chromatographies. The purified catalase exhibited higher
      catalytic efficiency and higher sensitivity of activity at high temperatures than
      M. luteus catalase. The deduced amino acid sequence showed the highest homology
      with catalase of Psycrobacter cryohalolentis, a psychrotolelant bacterium
      obtained from Siberian permafrost. These findings suggest that the
      characteristics of the PktA molecule reflected the taxonomic relationship of the
      isolate as well as the environmental conditions (low temperatures and high
      concentrations of H(2)O(2)) under which the bacterium survives. Strain T-3
      efficiently produces a catalase (PktA) at a higher rate than Exiguobacterium
      oxidotolerans, which produces a very strong activity of catalase (EktA) at a
      moderate rate, in order to adapt to high concentration of H(2)O(2).

PMID- 22408421
TI  - Mitochondrial protection and anti-aging activity of Astragalus polysaccharides
      and their potential mechanism.
AB  - The current study was performed to investigate mitochondrial protection and anti
      aging activity of Astragalus polysaccharides (APS) and the potential underlying
      mechanism. Lipid peroxidation of liver and brain mitochondria was induced by
      Fe(2+)-Vit C in vitro. Thiobarbituric acid (TBA) colorimetry was used to measure
      the content of thiobarbituric acid reactive substances (TBARS). Mouse liver
      mitochondrial permeability transition (PT) was induced by calcium overload in
      vitro and spectrophotometry was used to measure it. The scavenging activities of
      APS on superoxide anion (O(2) (*-)) and hydroxyl radical (*OH), which were
      produced by reduced nicotinamide adenine dinucleotide (NADH)-N-Methylphenazonium
      methyl sulfate (PMS) and hydrogen peroxide (H(2)O(2))-Fe(2+) system respectively,
      were measured by 4-nitrobluetetrazolium chloride (NBT) reduction and Fenton
      reaction colorimetry respectively. The Na(2)S(2)O(3) titration method was used to
      measure the scavenging activities of APS on H(2)O(2). APS could inhibit TBARS
      production, protect mitochondria from PT, and scavenge O(2) (*-), *OH and
      H(2)O(2) significantly in a concentration-dependent manner respectively. The back
      of the neck of mice was injected subcutaneously with D-galactose to induce aging
      at a dose of 100 mg/kg/d for seven weeks. Moreover, the activities of catalase
      (CAT), surperoxide dismutase (SOD) and glutathione peroxidase (GPx) and anti
      hydroxyl radical which were assayed by using commercial monitoring kits were
      increased significantly in vivo by APS. According to this research, APS protects
      mitochondria by scavenging reactive oxygen species (ROS), inhibiting
      mitochondrial PT and increasing the activities of antioxidases. Therefore, APS
      has the effect of promoting health.

PMID- 22408422
TI  - 10-Shogaol, an antioxidant from Zingiber officinale for skin cell proliferation
      and migration enhancer.
AB  - In this work, one of Zingiber officinale components, 10-shogaol, was tested with
      1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, metal chelating ability,
      and reducing power to show antioxidant activity. 10-Shogaol promoted human normal
      epidermal keratinocytes and dermal fibroblasts cell growths. 10-Shogaol enhanced
      growth factor production in transforming growth factor-beta (TGF-beta), platelet
      derived growth factor-alphabeta (PDGF-alphabeta) and vascular endothelial growth
      factors (VEGF) of both cells. In the in vitro wound healing assay for 12 or 24 h,
      with 10-shogaol, the fibroblasts and keratinocytes migrated more rapidly than the
      vehicle control group. Thus, this study substantiates the target compound, 10
      shogaol, as an antioxidant for human skin cell growth and a migration enhancer
      with potential to be a novel wound repair agent.

PMID- 22408423
TI  - Cinnamic acid and its derivatives inhibit fructose-mediated protein glycation.
AB  - Cinnamic acid and its derivatives have shown a variety of pharmacologic
      properties. However, little is known about the antiglycation properties of
      cinnamic acid and its derivatives. The present study sought to characterize the
      protein glycation inhibitory activity of cinnamic acid and its derivatives in a
      bovine serum albumin (BSA)/fructose system. The results demonstrated that
      cinnamic acid and its derivatives significantly inhibited the formation of
      advanced glycation end products (AGEs) by approximately 11.96-63.36% at a
      concentration of 1 mM. The strongest inhibitory activity against the formation of
      AGEs was shown by cinnamic acid. Furthermore, cinnamic acid and its derivatives
      reduced the level of fructosamine, the formation of N(E)-(carboxymethyl) lysine
      (CML), and the level of amyloid cross beta-structure. Cinnamic acid and its
      derivatives also prevented oxidative protein damages, including effects on
      protein carbonyl formation and thiol oxidation of BSA. Our findings may lead to
      the possibility of using cinnamic acid and its derivatives for preventing AGE
      mediated diabetic complications.

PMID- 22408424
TI  - Lipid peroxidative damage on Cisplatin exposure and alterations in antioxidant
      defense system in rat kidneys: a possible protective effect of selenium.
AB  - Cisplatin (Cis-diamminedichloroplatinum II, CP) is an important chemotherapeutic
      agent, useful in the treatment of several cancers, but with several side effects
      such as nephrotoxicity. The present study investigated the possible protective
      effect of selenium (Se) against CP-induced oxidative stress in the rat kidneys.
      Male Wistar albino rats were injected with a single dose of cisplatin (7 mg CP/kg
      b.m., i.p.) and selenium (6 mg Se/kg b.m, as Na(2)SeO(3), i.p.), alone or in
      combination. The obtained results showed that CP increased lipid peroxidation
      (LPO) and decreased reduced glutathione (GSH) concentrations, suggesting the CP
      induced oxidative stress, while Se treatment reversed this change to control
      values. Acute intoxication of rats with CP was followed by statistically
      significant decreased activity of antioxidant defense enzymes: superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione
      reductase (GR) and glutathione-S-transferase (GST). Treatment with Se reversed CP
      induced alterations of antioxidant defense enzyme activities and significantly
      prevented the CP-induced kidney damage.

PMID- 22408426
TI  - Aggregating data for computational toxicology applications: The U.S.
      Environmental Protection Agency (EPA) Aggregated Computational Toxicology
      Resource (ACToR) System.
AB  - Computational toxicology combines data from high-throughput test methods,
      chemical structure analyses and other biological domains (e.g., genes, proteins,
      cells, tissues) with the goals of predicting and understanding the underlying
      mechanistic causes of chemical toxicity and for predicting toxicity of new
      chemicals and products. A key feature of such approaches is their reliance on
      knowledge extracted from large collections of data and data sets in computable
      formats. The U.S. Environmental Protection Agency (EPA) has developed a large
      data resource called ACToR (Aggregated Computational Toxicology Resource) to
      support these data-intensive efforts. ACToR comprises four main repositories:
      core ACToR (chemical identifiers and structures, and summary data on hazard,
      exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a
      compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB
      (detailed human exposure data from observational studies of selected chemicals),
      and ToxCastDB (data from high-throughput screening programs, including links to
      underlying biological information related to genes and pathways). The EPA DSSTox
      (Distributed Structure-Searchable Toxicity) program provides expert-reviewed
      chemical structures and associated information for these and other high-interest
      public inventories. Overall, the ACToR system contains information on about
      400,000 chemicals from 1100 different sources. The entire system is built using
      open source tools and is freely available to download. This review describes the
      organization of the data repository and provides selected examples of use cases.

PMID- 22408427
TI  - Isolation and characterization of activators of ERK/MAPK from citrus plants.
AB  - Extracellular signal-regulated kinases 1/2 (ERK1/2), components of the mitogen
      activated protein kinase (MAPK) signaling cascade, have been recently shown to be
      involved in synaptic plasticity and in the development of long-term memory in the
      central nervous system (CNS). We therefore examined the ability of Citrus
      compounds to activate ERK1/2 in cultured rat cortical neurons, whose activation
      might have a protective effect against neurodegenerative neurological disorders.
      Among the samples tested, extracts prepared from the peels of Citrus grandis
      (Kawachi bankan) were found to have the greatest ability to activate ERK1/2. The
      active substances were isolated by chromatographic separation, and one of them
      was identified to be 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF). HMF significantly
      induced the phosphorylation of cAMP response element-binding protein (CREB), a
      downstream target of activated ERK1/2, which appears to be a critical step in the
      signaling cascade for the structural changes underlying the development of long
      term potentiation (LTP). In addition, the administration of HMF into mice treated
      with NMDA receptor antagonist MK-801 restored the MK-801-induced deterioration of
      spatial learning performance in the Morris mater-maze task. Taken together, these
      results suggest that HMF is a neurotrophic agent for treating patients with
      memory disorders.

PMID- 22408428
TI  - The -308G/A of Tumor Necrosis Factor (TNF)-alpha and 825C/T of Guanidine
      Nucleotide Binding Protein 3 (GNB3) are associated with the onset of acute
      myocardial infarction and obesity in Taiwan.
AB  - Acute myocardial infarction is a highly prevalent cardiovascular disease in
      Taiwan. Among several etiological risk factors, obesity and inflammation are
      strongly associated with the frequency of hypertension, cardiovascular disease,
      diabetes, and myocardial infarction. To discriminate obesity- and inflammation
      related genes and the onset of acute myocardial infarction (AMI), a case-control
      study was conducted to investigate the association of the -308G/A polymorphisms
      of tumor necrosis factor (TNF)-alpha and the C825T polymorphism of guanidine
      nucleotide binding protein 3 (GNB3) with the onset of AMI among Taiwanese
      cohorts. A total of 103 AMI patients and 163 matched normal control samples were
      enrolled in the present study. The genomic DNA was extracted and subjected into
      polymerase chain reaction-based restriction fragment length polymorphism (PCR
      RFLP) analysis. An association between the A homozygosity of the TNF-alpha-308G/A
      polymorphism and the onset of AMI was observed among the male subjects (p =
      0.026; Spearman index = 0.200, p = 0.008). An association between the T
      homozygosity of GNB3 C825T polymorphism and obesity was also observed (Fisher's
      exact, p = 0.009). The TT genotype has a protective effect against acquiring AMI
      among the obese female population in Taiwan (Fisher's exact, p = 0.032). In
      conclusion, TNF-alpha-308G/A and the GNB3 C825T polymorphisms are associated with
      obesity and AMI in the Taiwanese population.

PMID- 22408429
TI  - Yeast mitochondrial interactosome model: metabolon membrane proteins complex
      involved in the channeling of ADP/ATP.
AB  - The existence of a mitochondrial interactosome (MI) has been currently well
      established in mammalian cells but the exact composition of this super-complex is
      not precisely known, and its organization seems to be different from that in
      yeast. One major difference is the absence of mitochondrial creatine kinase
      (MtCK) in yeast, unlike that described in the organization model of MI,
      especially in cardiac, skeletal muscle and brain cells. The aim of this review is
      to provide a detailed description of different partner proteins involved in the
      synergistic ADP/ATP transport across the mitochondrial membranes in the yeast
      Saccharomyces cerevisiae and to propose a new mitochondrial interactosome model.
      The ADP/ATP (Aacp) and inorganic phosphate (PiC) carriers as well as the VDAC (or
      mitochondrial porin) catalyze the import and export of ADP, ATP and Pi across the
      mitochondrial membranes. Aacp and PiC, which appear to be associated with the ATP
      synthase, consist of two nanomotors (F(0), F(1)) under specific conditions and
      form ATP synthasome. Identification and characterization of such a complex were
      described for the first time by Pedersen and co-workers in 2003.

PMID- 22408431
TI  - Presence of CP4-EPSPS component in roundup ready soybean-derived food products.
AB  - With the widespread use of Roundup Ready soya (event 40-3-2) (RRS), the
      traceability of transgenic components, especially protein residues, in different
      soya-related foodstuffs has become an important issue. In this report, transgenic
      components in commercial soya (including RRS) protein concentrates were firstly
      detected by using polymerase chain reaction (PCR) and western blot. The results
      illustrated the different degradation patterns of the cp4-epsps gene and
      corresponding protein in RRS-derived protein concentrates. Furthermore, western
      blot was applied to investigate the single factor of food processing and the
      matrix on the disintegration of CP4-EPSPS protein in RRS powder and soya-derived
      foodstuffs, and trace the degradation patterns during the food production chain.
      Our results suggested that the exogenous full length of CP4-EPSPS protein in RRS
      powder was distinctively sensitive to various heat treatments, including heat,
      microwave and autoclave (especially), and only one degradation fragment (23.4 kD)
      of CP4-EPSPS protein was apparently observed when autoclaving was applied. By
      tracing the protein degradation during RRS-related products, including tofu, tou
      kan, and bean curd sheets, however, four degradation fragments (42.9, 38.2, 32.2
      and 23.4 kD) were displayed, suggesting that both boiling and bittern adding
      procedures might have extensive effects on CP4-EPSPS protein degradation. Our
      results thus confirmed that the distinctive residues of the CP4-EPSPS component
      could be traced in RRS-related foodstuffs.

PMID- 22408430
TI  - The mTOR signalling pathway in human cancer.
AB  - The conserved serine/threonine kinase mTOR (the mammalian target of rapamycin), a
      downstream effector of the PI3K/AKT pathway, forms two distinct multiprotein
      complexes: mTORC1 and mTORC2. mTORC1 is sensitive to rapamycin, activates S6K1
      and 4EBP1, which are involved in mRNA translation. It is activated by diverse
      stimuli, such as growth factors, nutrients, energy and stress signals, and
      essential signalling pathways, such as PI3K, MAPK and AMPK, in order to control
      cell growth, proliferation and survival. mTORC2 is considered resistant to
      rapamycin and is generally insensitive to nutrients and energy signals. It
      activates PKC-alpha and AKT and regulates the actin cytoskeleton. Deregulation of
      multiple elements of the mTOR pathway (PI3K amplification/mutation, PTEN loss of
      function, AKT overexpression, and S6K1, 4EBP1 and eIF4E overexpression) has been
      reported in many types of cancers, particularly in melanoma, where alterations in
      major components of the mTOR pathway were reported to have significant effects on
      tumour progression. Therefore, mTOR is an appealing therapeutic target and mTOR
      inhibitors, including the rapamycin analogues deforolimus, everolimus and
      temsirolimus, are submitted to clinical trials for treating multiple cancers,
      alone or in combination with inhibitors of other pathways. Importantly,
      temsirolimus and everolimus were recently approved by the FDA for the treatment
      of renal cell carcinoma, PNET and giant cell astrocytoma. Small molecules that
      inhibit mTOR kinase activity and dual PI3K-mTOR inhibitors are also being
      developed. In this review, we aim to survey relevant research, the molecular
      mechanisms of signalling, including upstream activation and downstream effectors,
      and the role of mTOR in cancer, mainly in melanoma.

PMID- 22408432
TI  - Glucose-modulated mitochondria adaptation in tumor cells: a focus on ATP synthase
      and inhibitor Factor 1.
AB  - Warburg's hypothesis has been challenged by a number of studies showing that
      oxidative phosphorylation is repressed in some tumors, rather than being inactive
      per se. Thus, treatments able to shift energy metabolism by activating
      mitochondrial pathways have been suggested as an intriguing basis for the
      optimization of antitumor strategies. In this study, HepG2 hepatocarcinoma cells
      were cultivated with different metabolic substrates under conditions mimicking
      "positive" (activation/biogenesis) or "negative" (silencing) mitochondrial
      adaptation. In addition to the expected up-regulation of mitochondrial
      biogenesis, glucose deprivation caused an increase in phosphorylating respiration
      and a rise in the expression levels of the ATP synthase beta subunit and
      Inhibitor Factor 1 (IF1). Hyperglycemia, on the other hand, led to a markedly
      decreased level of the transcriptional coactivator PGC-alpha suggesting down
      regulation of mitochondrial biogenesis, although no change in mitochondrial mass
      and no impairment of phosphorylating respiration were observed. Moreover, a
      reduction in mitochondrial networking and in ATP synthase dimer stability was
      produced. No effect on beta-ATP synthase expression was elicited. Notably,
      hyperglycemia caused an increase in IF1 expression levels, but it did not alter
      the amount of IF1 associated with ATP synthase. These results point to a new role
      of IF1 in relation to high glucose utilization by tumor cells, in addition to its
      well known effect upon mitochondrial ATP synthase regulation.

PMID- 22408434
TI  - Effect of the leaving group and solvent combination on the LFER reaction
      constants.
AB  - Fine effects that influence the variations of the reaction constants s(f) in LFER
      log k = s(f)(N(f) + E(f)) have been summarized here. Increasing solvent polarity
      in the series of binary mixtures increases the solvolysis rates for the same
      factor for all benzhydryl derivatives in which the solvation of the leaving group
      moiety in the transition state is substantial, i.e., log k vs. E(f) correlation
      lines are parallel (same s(f)). For the substrates in which the demand for
      solvation of the leaving groups moiety is reduced, (e.g., carbonates) s(f)
      parameters decrease as the fraction of the water in a given solvent/water mixture
      increases (log k vs. E(f) plots converge), due to decreasing solvation of the
      electrofuge moiety toward bigger electrofugality. The abscissa of the
      intersection of the converging plots might indicate the critical electrofugality
      above which the solvolysis rates should not depend of the water fraction. Larger
      reaction constant s(f) indicate later transition state for structurally related
      substrates only, while s(f) parameters for structurally different substrates
      cannot be compared likely due to different intrinsic barriers. Inversion in
      relative abilities of leaving groups is possible if they have similar
      reactivities and are characterized with different reaction constants.

PMID- 22408435
TI  - Bufalin induces lung cancer cell apoptosis via the inhibition of PI3K/Akt
      pathway.
AB  - Bufalin is a class of toxic steroids which could induce the differentiation and
      apoptosis of leukemia cells, and induce the apoptosis of gastric, colon and
      breast cancer cells. However, the anti-tumor effects of bufalin have not been
      demonstrated in lung cancer. In this study we used A549 human lung adenocarcinoma
      epithelial cell line as the experimental model to evaluate the potential of
      bufalin in lung cancer chemotherapy. A549 cells were treated with bufalin, then
      the proliferation was detected by MTT assay and apoptosis was detected by flow
      cytometry analysis and Giemsa staining. In addition, A549 cells were treated by
      Akt inhibitor LY294002 in combination with bufalin and the activation of Akt and
      Caspase-3 as well as the expression levels of Bax, Bcl-2 and livin were examined
      by Western blot analysis. The results showed that Bufalin inhibited the
      proliferation of A549 cells and induced the apoptosis of A549 cells in a dose and
      time dependent manner. Mechanistically, we found that bufalin inhibited the
      activation of Akt. Moreover, bufalin synergized with Akt inhibitor to induce the
      apoptosis of A549 cells and this was associated with the upregulation of Bax
      expression, the downregulation of Bcl-2 and livin expression, and the activation
      of Caspase-3. In conclusion, our findings demonstrate that bufalin induces lung
      cancer cell apoptosis via the inhibition of PI3K/Akt pathway and suggest that
      bufalin is a potential regimen for combined chemotherapy to overcome the
      resistance of lung cancer cells to chemotherapeutics induced apoptosis.

PMID- 22408436
TI  - Influence of post-treatment with 75% (v/v) ethanol vapor on the properties of
      SF/P(LLA-CL) nanofibrous scaffolds.
AB  - In order to improve the water-resistant ability of silk fibroin (SF) and SF/P(LLA
      CL) blended nanofibrous scaffolds for tissue engineering applications, 75% (v/v)
      ethanol vapor was used to post-treat electrospun nanofibers. SEM indicated that
      the treated SF and SF/P(LLA-CL) nanofibrous scaffolds maintained a nanofibrous
      structure and possessed good water-resistant ability. Characterization of (13)C
      CP-MAS NMR clarified that 75% (v/v) ethanol vapor could induce SF conformation
      from random coil or alpha-helix to beta-sheet. Although the water contact showed
      that treated SF/P(LLA-CL) blended nanofibrous scaffolds were hydrophobic, the
      water uptake demonstrated that their hydrophilicity was greatly superior to those
      of pure P(LLA-CL) nanofibrous scaffolds. Furthermore, the treated SF/P(LLA-CL)
      nanofibrous scaffolds, both in dry state and wet state, could retain good
      mechanical properties. Therefore, 75% (v/v) ethanol vapor treatment might be an
      ideal method to treat SF and SF/P(LLA-CL) nanofibrous scaffolds for biomedical
      applications.

PMID- 22408433
TI  - Tumor heterogeneity: mechanisms and bases for a reliable application of molecular
      marker design.
AB  - Tumor heterogeneity is a confusing finding in the assessment of neoplasms,
      potentially resulting in inaccurate diagnostic, prognostic and predictive tests.
      This tumor heterogeneity is not always a random and unpredictable phenomenon,
      whose knowledge helps designing better tests. The biologic reasons for this
      intratumoral heterogeneity would then be important to understand both the natural
      history of neoplasms and the selection of test samples for reliable analysis. The
      main factors contributing to intratumoral heterogeneity inducing gene
      abnormalities or modifying its expression include: the gradient ischemic level
      within neoplasms, the action of tumor microenvironment (bidirectional interaction
      between tumor cells and stroma), mechanisms of intercellular transference of
      genetic information (exosomes), and differential mechanisms of sequence
      independent modifications of genetic material and proteins. The intratumoral
      heterogeneity is at the origin of tumor progression and it is also the byproduct
      of the selection process during progression. Any analysis of heterogeneity
      mechanisms must be integrated within the process of segregation of genetic
      changes in tumor cells during the clonal expansion and progression of neoplasms.
      The evaluation of these mechanisms must also consider the redundancy and
      pleiotropism of molecular pathways, for which appropriate surrogate markers would
      support the presence or not of heterogeneous genetics and the main mechanisms
      responsible. This knowledge would constitute a solid scientific background for
      future therapeutic planning.

PMID- 22408437
TI  - PCR and magnetic bead-mediated target capture for the isolation of short
      interspersed nucleotide elements in fishes.
AB  - Short interspersed nucleotide elements (SINEs), a type of retrotransposon, are
      widely distributed in various genomes with multiple copies arranged in different
      orientations, and cause changes to genes and genomes during evolutionary history.
      This can provide the basis for determining genome diversity, genetic variation
      and molecular phylogeny, etc. SINE DNA is transcribed into RNA by polymerase III
      from an internal promoter, which is composed of two conserved boxes, box A and
      box B. Here we present an approach to isolate novel SINEs based on these promoter
      elements. Box A of a SINE is obtained via PCR with only one primer identical to
      box B (B-PCR). Box B and its downstream sequence are acquired by PCR with one
      primer corresponding to box A (A-PCR). The SINE clone produced by A-PCR is
      selected as a template to label a probe with biotin. The full-length SINEs are
      isolated from the genomic pool through complex capture using the biotinylated
      probe bound to magnetic particles. Using this approach, a novel SINE family, Cn
      SINE, from the genomes of Coilia nasus, was isolated. The members are 180-360 bp
      long. Sequence homology suggests that Cn-SINEs evolved from a leucine tRNA gene.
      This is the first report of a tRNA(Leu)-related SINE obtained without the use of
      a genomic library or inverse PCR. These results provide new insights into the
      origin of SINEs.

PMID- 22408438
TI  - ACVR1, a therapeutic target of fibrodysplasia ossificans progressiva, is
      negatively regulated by miR-148a.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder of
      skeletal malformations and progressive extraskeletal ossification. There is still
      no effective treatment for FOP. All FOP individuals harbor conserved point
      mutations in ACVR1 gene that are thought to cause ACVR1 constitutive activation
      and activate BMP signal pathway. The constitutively active ACVR1 is also found to
      be able to cause endothelial-to-mesenchymal transition (EndMT) in endothelial
      cells, which may cause the formation of FOP lesions. MicroRNAs (miRNAs) play an
      essential role in regulating cell differentiation. Here, we verified that miR
      148a directly targeted the 3' UTR of ACVR1 mRNA by reporter gene assays and
      mutational analysis at the miRNA binding sites, and inhibited ACVR1 both at the
      protein level and mRNA level. Further, we verified that miR-148a could inhibit
      the mRNA expression of the Inhibitor of DNA binding (Id) gene family thereby
      suppressing the BMP signaling pathway. This study suggests miR-148a is an
      important mediator of ACVR1, thus offering a new potential target for the
      development of therapeutic agents against FOP.

PMID- 22408439
TI  - Neuroprotective effects of pre-treatment with l-carnitine and acetyl-L-carnitine
      on ischemic injury in vivo and in vitro.
AB  - The therapeutic effect of stroke is hampered by the lack of neuroprotective drugs
      against ischemic insults beyond the acute phase. Carnitine plays important roles
      in mitochondrial metabolism and in modulating the ratio of coenzyme A (CoA)/acyl
      CoA. Here, we investigate the neuroprotective effects of l-carnitine (LC) and
      Acetyl-l-carnitine (ALC) pre-treatment on ischemic insults under the same
      experimental conditions. We used a transient middle cerebral artery occlusion
      (MCAO) model to evaluate the protective roles of LC and ALC in acute focal
      cerebral ischemia in vivo and to understand the possible mechanisms using model
      of PC12 cell cultures in vitro. Results showed that ALC, but not LC, decreased
      infarction size in SD rats after MCAO in vivo. However, both LC and ALC
      pretreatment reduced oxygen-glucose deprivation (OGD)-induced cell injury and
      decreased OGD-induced cell apoptosis and death in vitro; at the same time, both
      of them increased the activities of super oxide dismutase (SOD) and ATPase, and
      decreased the concentration of malondialdehyde (MDA) in vitro. Thus, our findings
      suggested that LC and ALC pre-treatment are highly effective in the prevention of
      neuronal cell against ischemic injury in vitro, however, only ALC has the
      protective effect on neuronal cell injury after ischemia in vivo.

PMID- 22408440
TI  - Antioxidant-induced stress.
AB  - Antioxidants are among the most popular health-protecting products, sold
      worldwide without prescription. Indeed, there are many reports showing the
      benefits of antioxidants but only a few questioning the possible harmful effects
      of these "drugs". The normal balance between antioxidants and free radicals in
      the body is offset when either of these forces prevails. The available evidence
      on the harmful effects of antioxidants is analyzed in this review. In summary, a
      hypothesis is presented that "antioxidant-induced stress" results when
      antioxidants overwhelm the body's free radicals.

PMID- 22408441
TI  - The effect of toll-like receptor 4 in the aqueous humor of endotoxin-induced
      uveitis.
AB  - In our previous study, we found that acute anterior uveitis (AAU) could be
      induced in wild-type mice (C3H/HeN), but it could not be induced in TLR4 gene
      deficient mice (C3H/HeJ), we concluded that the translocation of transcription
      factor nuclear factor-kappaB (NF-kappaB) may play an important role. In this
      study, we examined the concentration of different cytokines in the aqueous humor
      of C3H/HeN mice and C3H/HeJ mice with the aim of exploring the role of different
      cytokines in the lipopolysaccharide (LPS) and TLR4-mediated signal transduction
      in the development of AAU.

PMID- 22408442
TI  - Correlation coefficients between different methods of expressing bacterial
      quantification using real time PCR.
AB  - The applications of conventional culture-dependent assays to quantify bacteria
      populations are limited by their dependence on the inconsistent success of the
      different culture-steps involved. In addition, some bacteria can be pathogenic or
      a source of endotoxins and pose a health risk to the researchers. Bacterial
      quantification based on the real-time PCR method can overcome the above-mentioned
      problems. However, the quantification of bacteria using this approach is commonly
      expressed as absolute quantities even though the composition of samples (like
      those of digesta) can vary widely; thus, the final results may be affected if the
      samples are not properly homogenized, especially when multiple samples are to be
      pooled together before DNA extraction. The objective of this study was to
      determine the correlation coefficients between four different methods of
      expressing the output data of real-time PCR-based bacterial quantification. The
      four methods were: (i) the common absolute method expressed as the cell number of
      specific bacteria per gram of digesta; (ii) the Livak and Schmittgen,
      DeltaDeltaCt method; (iii) the Pfaffl equation; and (iv) a simple relative method
      based on the ratio of cell number of specific bacteria to the total bacterial
      cells. Because of the effect on total bacteria population in the results obtained
      using DeltaCt-based methods (DeltaDeltaCt and Pfaffl), these methods lack the
      acceptable consistency to be used as valid and reliable methods in real-time PCR
      based bacterial quantification studies. On the other hand, because of the
      variable compositions of digesta samples, a simple ratio of cell number of
      specific bacteria to the corresponding total bacterial cells of the same sample
      can be a more accurate method to quantify the population.

PMID- 22408443
TI  - cDNA cloning, overexpression, purification and pharmacologic evaluation for
      anticancer activity of ribosomal protein L23A gene (RPL23A) from the Giant Panda.
AB  - RPL23A gene encodes a ribosomal protein that is a component of the 60S subunit.
      The protein belongs to the L23P family of ribosomal proteins, which is located in
      the cytoplasm. The purpose of this paper was to explore the structure and anti
      cancer function of ribosomal protein L23A (RPL23A) gene of the Giant Panda
      (Ailuropoda melanoleuca). The cDNA of RPL23A was cloned successfully from the
      Giant Panda using RT-PCR technology. We constructed a recombinant expression
      vector containing RPL23A cDNA and over-expressed it in Escherichia coli using
      pET28a plasmids. The expression product obtained was purified by using Ni
      chelating affinity chromatography. Recombinant protein of RPL23A obtained from
      the experiment acted on Hep-2 cells and human HepG-2 cells, then the growth
      inhibitory effect of these cells was observed by MTT (3-[4,5-dimethyl-2
      thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide) assay. The result indicated that
      the length of the fragment cloned is 506 bp, and it contains an open-reading
      frame (ORF) of 471 bp encoding 156 amino acids. Primary structure analysis
      revealed that the molecular weight of the putative RPL23A protein is 17.719 kDa
      with a theoretical pI 11.16. The molecular weight of the recombinant protein
      RPL23A is 21.265 kDa with a theoretical pI 10.57. The RPL23A gene can be really
      expressed in E. coli and the RPL23A protein, fusioned with the N-terminally His
      tagged protein, gave rise to the accumulation of an expected 22 KDa polypeptide.
      The data showed that the recombinant protein RPL23A had a time- and dose
      dependency on the cell growth inhibition rate. The data also indicated that the
      effect at low concentrations was better than at high concentrations on Hep-2
      cells, and that the concentration of 0.185 MUg/mL had the best rate of growth
      inhibition of 36.31%. All results of the experiment revealed that the recombinant
      protein RPL23A exhibited anti-cancer function on the Hep-2 cells. The study
      provides a scientific basis and aids orientation for the research and development
      of cancer protein drugs as well as possible anti-cancer mechanisms. Further
      research is on going to determine the bioactive principle(s) of recombinant
      protein RPL23A responsible for its anticancer activity.

PMID- 22408444
TI  - Benzyl and methyl fatty hydroxamic acids based on palm kernel oil as chelating
      agent for liquid-liquid iron(III) extraction.
AB  - Liquid-liquid iron(III) extraction was investigated using benzyl fatty hydroxamic
      acids (BFHAs) and methyl fatty hydroxamic acids (MFHAs) as chelating agents
      through the formation of iron(III) methyl fatty hydroxamate (Fe-MFHs) or
      iron(III) benzyl fatty hydroxamate (Fe-BFHs) in the organic phase. The results
      obtained under optimized conditions, showed that the chelating agents in hexane
      extract iron(III) at pH 1.9 were realized effectively with a high percentage of
      extraction (97.2% and 98.1% for MFHAs and BFHAs, respectively). The presence of a
      large amount of Mg(II), Ni(II), Al(III), Mn(II) and Co(II) ions did affect the
      iron(III) extraction. Finally stripping studies for recovering iron(III) from
      organic phase (Fe-MFHs or Fe-BFHs dissolved in hexane) were carried out at
      various concentrations of HCl, HNO(3) and H(2)SO(4). The results showed that the
      desired acid for recovery of iron(III) was 5 M HCl and quantitative recovery of
      iron(III) was achieved from Fe(III)-MFHs and Fe(III)-BFHs solutions in hexane
      containing 5 mg/L of Fe(III).

PMID- 22408445
TI  - On the electrophilic character of molecules through its relation with
      electronegativity and chemical hardness.
AB  - Electrophilicity is an intrinsic property of atoms and molecules. It probably
      originates logistically with the involvement in the physical process of
      electrostatics of soaked charge in electronic shells and the screened nuclear
      charge of atoms. Motivated by the existing view of conceptual density functional
      theory that similar to electronegativity and hardness equalization, there should
      be a physical process of equalization of electrophilicity during the chemical
      process of formation of hetero nuclear molecules, we have developed a new
      theoretical scheme and formula for evaluating the electrophilicity of hetero
      nuclear molecules. A comparative study with available bench marking reveals that
      the hypothesis of electrophilicity and equalization, and the present method of
      evaluating equalized electrophilicity, are scientifically promising.

PMID- 22408446
TI  - Computational studies of difference in binding modes of peptide and non-peptide
      inhibitors to MDM2/MDMX based on molecular dynamics simulations.
AB  - Inhibition of p53-MDM2/MDMX interaction is considered to be a promising strategy
      for anticancer drug design to activate wild-type p53 in tumors. We carry out
      molecular dynamics (MD) simulations to study the binding mechanisms of peptide
      and non-peptide inhibitors to MDM2/MDMX. The rank of binding free energies
      calculated by molecular mechanics generalized Born surface area (MM-GBSA) method
      agrees with one of the experimental values. The results suggest that van der
      Waals energy drives two kinds of inhibitors to MDM2/MDMX. We also find that the
      peptide inhibitors can produce more interaction contacts with MDM2/MDMX than the
      non-peptide inhibitors. Binding mode predictions based on the inhibitor-residue
      interactions show that the pi-pi, CH-pi and CH-CH interactions dominated by shape
      complimentarity, govern the binding of the inhibitors in the hydrophobic cleft of
      MDM2/MDMX. Our studies confirm the residue Tyr99 in MDMX can generate a steric
      clash with the inhibitors due to energy and structure. This finding may
      theoretically provide help to develop potent dual-specific or MDMX inhibitors.

PMID- 22408447
TI  - Using support vector machine and evolutionary profiles to predict antifreeze
      protein sequences.
AB  - Antifreeze proteins (AFPs) are ice-binding proteins. Accurate identification of
      new AFPs is important in understanding ice-protein interactions and creating
      novel ice-binding domains in other proteins. In this paper, an accurate method,
      called AFP_PSSM, has been developed for predicting antifreeze proteins using a
      support vector machine (SVM) and position specific scoring matrix (PSSM)
      profiles. This is the first study in which evolutionary information in the form
      of PSSM profiles has been successfully used for predicting antifreeze proteins.
      Tested by 10-fold cross validation and independent test, the accuracy of the
      proposed method reaches 82.67% for the training dataset and 93.01% for the
      testing dataset, respectively. These results indicate that our predictor is a
      useful tool for predicting antifreeze proteins. A web server (AFP_PSSM) that
      implements the proposed predictor is freely available.

PMID- 22408448
TI  - A novel LMP1 antibody synergizes with mitomycin C to inhibit nasopharyngeal
      carcinoma growth in vivo through inducing apoptosis and downregulating vascular
      endothelial growth factor.
AB  - Combined therapy emerges as an attractive strategy for cancer treatment. The aim
      of this study was to investigate the inhibitory effects of mitomycin C (MMC)
      combined with a novel antibody fragment (Fab) targeting latent membrane protein 1
      (LMP1) on nasopharyngeal carcinoma (NPC) xenograft nude mice. The inhibitory
      rates of MMC (2 mg/kg), Fab (4 mg/kg), MMC (2 mg/kg) + Fab (4 mg/kg), and MMC (1
      mg/kg) + Fab (4 mg/kg) were 20.1%, 7.3%, 42.5% and 40.5%, respectively. Flow
      cytometry analysis showed that the apoptotic rate of xenograft tumor cells in the
      MMC and Fab combination group was 28 +/- 4.12%, significantly higher than the MMC
      (2 mg/kg) group (P < 0.01). Immunohistochemical staining showed that VEGF
      expression in NPC xenografts was significantly inhibited in the combination group
      compared to the Fab (4 mg/kg) group (P < 0.05). In conclusion, both MMC and Fab
      could inhibit NPC xenograft tumor growth in vivo and combination therapy showed
      apparent synergistic anti-tumor effects, which may be due to the induction of
      tumor cell apoptosis and the downregulation of VEGF expression. These results
      suggest that the novel combined therapy utilizing traditional chemotherapeutics
      and antibody-targeted therapy could be a promising strategy for the treatment of
      NPC.

PMID- 22408450
TI  - Nanosecond T-jump experiment in poly(glutamic acid): a circular dichroism study.
AB  - Poly(glutamic acid) has been studied with a nanosecond T-jump experiment. A new
      experimental set-up based on the frequency-quadrupling of an 82 MHz Titanium
      Sapphire laser allows rapid CD measurements to be performed. Combining time
      resolved absorption and circular dichroism at 204 and 220 nm, we are able to
      measure precisely the unfolding relaxation time as well as the helical fraction
      evolution. We show that only CD at 220 nm is relevant to observe the unfolding of
      an alpha helix whereas no change is observed for CD at 204 nm. Conversely, both
      absorptions yield information on the dynamics of the process.

PMID- 22408449
TI  - Alpha7 nicotinic acetylcholine receptor is a target in pharmacology and
      toxicology.
AB  - Alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) is an important part of
      the cholinergic nerve system in the brain. Moreover, it is associated with a
      cholinergic anti-inflammatory pathway in the termination of the parasympathetic
      nervous system. Antagonists of alpha7 nAChR are a wide group represented by
      conotoxin and bungarotoxin. Even Alzheimer's disease drug memantine acting as an
      antagonist in its side pathway belongs in this group. Agonists of alpha7 nAChR
      are suitable for treatment of multiple cognitive dysfunctions such as Alzheimer's
      disease or schizophrenia. Inflammation or even sepsis can be ameliorated by the
      agonistic acting compounds. Preparations RG3487, SEN34625/WYE-103914, SEN12333,
      ABT-107, Clozapine, GTS-21, CNI-1493, and AR-R17779 are representative examples
      of the novel compounds with affinity toward the alpha7 nAChR. Pharmacological,
      toxicological, and medicinal significance of alpha7 nAChR are discussed
      throughout this paper.

PMID- 22408451
TI  - Seasonal variations of the antioxidant composition in ground bamboo Sasa
      argenteastriatus leaves.
AB  - Sasa argenteastriatus, with abundant active compounds and high antioxidant
      activity in leaves, is a new leafy bamboo grove suitable for exploitation. To
      utilize it more effectively and scientifically, we investigate the seasonal
      variations of antioxidant composition in its leaves and antioxidant activity. The
      leaves of Sasa argenteastriatus were collected on the 5th day of each month in
      three same-sized sample plots from May 2009 to May 2011. The total flavonoids
      (TF): phenolics (TP) and triterpenoid (TT) of bamboo leaves were extracted and
      the contents analyzed by UV-spectrophotometer. Our data showed that all exhibited
      variations with the changing seasons, with the highest levels appearing in
      November to March. Antioxidant activity was measured using DPPH and FRAP methods.
      The highest antioxidant activity appeared in December with the lowest in May.
      Correlation analyses demonstrated that TP and TF exhibited high correlation with
      bamboo antioxidant activity. Eight bamboo characteristic compounds (orientin,
      isoorientin, vitexin, homovitexin and p-coumaric acid, chlorogenic acid, caffeic
      acid, ferulic acid) were determined by RP-HPLC synchronously. We found that
      chlorogenic acid, isoorientin and vitexin are the main compounds in Sasa
      argenteastriatus leaves and the content of isovitexin and chlorogenic acid showed
      a similar seasonal variation with the TF, TP and TT. Our results suggested that
      the optimum season for harvesting Sasa argenteastriatus leaves is between autumn
      and winter.

PMID- 22408452
TI  - Comprehensive and facile synthesis of some functionalized bis-heterocyclic
      compounds containing a thieno[2,3-b]thiophene motif.
AB  - A comprehensive and facile method for the synthesis of new functionalized bis
      heterocyclic compounds containing a thieno[2,3-b]thiophene motif is described.
      The hitherto unknown bis-pyrazolothieno[2,3-b]thiophene derivatives 2a-c, bis
      pyridazin othieno[2,3-b]thiophene derivatives 4, bis-pyridinothieno[2,3
      b]thiophene derivatives 6a,b, and to an analogous bis-pyridinothieno[2,3
      b]thiophene nitrile derivatives 7 are obtained. Additionally, the novel bis
      pyradazinonothieno[2,3-b]thiophene derivatives 9, and nicotinic acid derivatives
      10, 11 are obtained via bis-dienamide 8. The structures of all newly synthesized
      compounds have been elucidated by (1)H, (13)C NMR, GCMS, and IR spectrometry.
      These compounds represent a new class of sulfur and Nitrogen containing
      heterocycles that should also be of interest as new materials.

PMID- 22408453
TI  - Emodin prevents intrahepatic fat accumulation, inflammation and redox status
      imbalance during diet-induced hepatosteatosis in rats.
AB  - High-fat and/or high-carbohydrate diets may predispose to several metabolic
      disturbances including liver fatty infiltration (hepatosteatosis) or be
      associated with necro-inflammation and fibrosis (steatohepatitis). Several
      studies have emphasized the hepatoprotective effect of some natural agents. In
      this study, we investigated the potential therapeutic effects of the treatment
      with emodin, an anthraquinone derivative with anti-oxidant and anti-cancer
      abilities, in rats developing diet-induced hepatosteatosis and steatohepatitis.
      Sprague-Dawley rats were fed a standard diet (SD) for 15 weeks, or a high
      fat/high-fructose diet (HFD/HF). After 5 weeks, emodin was added to the drinking
      water of some of the SD and HFD/HF rats. The experiment ended after an additional
      10 weeks. Emodin-treated HFD/HF rats were protected from hepatosteatosis and
      metabolic derangements usually observed in HFD/HF animals. Furthermore, emodin
      exerted anti-inflammatory activity by inhibiting the HFD/HF-induced increase of
      tumor necrosis factor (TNF)-alpha. Emodin also affected the hepatocytes
      glutathione homeostasis and levels of the HFD/HF-induced increase of
      glutathionylated/phosphorylated phosphatase and tensin homolog (PTEN). In
      conclusion, we demonstrated that a natural agent such as emodin can prevent
      hepatosteatosis, preserving liver from pro-inflammatory and pro-oxidant damage
      caused by HFD/HF diet. These findings are promising, proposing emodin as a
      possible hindrance to progression of hepatosteatosis into steatohepatitis.

PMID- 22408454
TI  - In vitro control of post-harvest fruit rot fungi by some plant essential oil
      components.
AB  - Eight substances that are main components of the essential oils from three
      Mediterranean aromatic plants (Verbena officinalis, Thymus vulgaris and Origanum
      vulgare), previously found active against some phytopathogenic Fungi and
      Stramenopila, have been tested in vitro against five etiological agents of post
      harvest fruit decay, Botrytis cinerea, Penicillium italicum, P. expansum,
      Phytophthora citrophthora and Rhizopus stolonifer. The tested compounds were beta
      fellandrene, beta-pinene, camphene, carvacrol, citral, o-cymene, gamma-terpinene
      and thymol. Citral exhibited a fungicidal action against P. citrophthora;
      carvacrol and thymol showed a fungistatic activity against P. citrophthora and R.
      stolonifer. Citral and carvacrol at 250 ppm, and thymol at 150 and 250 ppm
      stopped the growth of B. cinerea. Moreover, thymol showed fungistatic and
      fungicidal action against P. italicum. Finally, the mycelium growth of P.
      expansum was inhibited in the presence of 250 ppm of thymol and carvacrol. These
      results represent an important step toward the goal to use some essential oils or
      their components as natural preservatives for fruits and foodstuffs, due to their
      safety for consumer healthy and positive effect on shelf life extension of
      agricultural fresh products.

PMID- 22408455
TI  - Expression patterns of genes involved in the defense and stress response of
      Spiroplasma citri infected Madagascar Periwinkle Catharanthus roseus.
AB  - Madagascar periwinkle is an ornamental and a medicinal plant, and is also an
      indicator plant that is highly susceptible to phytoplasma and spiroplasma
      infections from different crops. Periwinkle lethal yellows, caused by Spiroplasma
      citri, is one of the most devastating diseases of periwinkle. The response of
      plants to S. citri infection is very little known at the transcriptome level. In
      this study, quantitative real-time PCR (RT-qPCR) was used to investigate the
      expression levels of four selected genes involved in defense and stress responses
      in naturally and experimentally Spiroplasma citri infected periwinkles.
      Strictosidine beta-glucosidase involved in terpenoid indole alkaloids (TIAs)
      biosynthesis pathway showed significant upregulation in experimentally and
      naturally infected periwinkles. The transcript level of extensin increased in
      leaves of periwinkles experimentally infected by S. citri in comparison to
      healthy ones. A similar level of heat shock protein 90 and metallothionein
      expression was observed in healthy, naturally and experimentally spiroplasma
      diseased periwinkles. Overexpression of Strictosidine beta-glucosidase
      demonstrates the potential utility of this gene as a host biomarker to increase
      the fidelity of S. citri detection and can also be used in breeding programs to
      develop stable disease-resistance varieties.

PMID- 22408456
TI  - Antioxidant and hepatoprotective effects of the red ginseng essential oil in
      H(2)O(2)-treated hepG2 cells and CCl(4)-treated mice.
AB  - The aim of this study was to evaluate the antioxidant mechanisms of red ginseng
      essential oil (REO) in cells as well as in an animal model. REO was prepared by a
      supercritical CO(2) extraction of waste-products generated after hot water
      extraction of red ginseng. In HepG2 cells, REO diminished the H(2)O(2)-mediated
      oxidative stress and also restored both the activity and expression of
      antioxidant enzymes such as superoxide dismutase, catalase and glutathione
      peroxidase. Administration of REO inhibited the phosphorylation of upstream
      mitogen-activated protein kinases (MAPKs) such as c-Jun N-terminal kinase,
      extracellular signal-regulated kinase, and p38. In mice, the CCl(4)-mediated
      elevation of serum aspartate transaminase and alanine transaminase as well as the
      induction of hepatic lipid peroxidation were decreased by REO administration. REO
      treatments also resulted in up-regulation of the antioxidant enzyme expression in
      the liver. Moreover, increased phosphorylations of MAPKs were inhibited after REO
      administration. Overall, REO seems to protect the liver from oxidative stress
      through the activation and induction of antioxidant enzymes via inhibition of
      MAPKs pathways.

PMID- 22408458
TI  - Supercritical carbon dioxide extraction of the Oak Silkworm (Antheraea pernyi)
      Pupal Oil: process optimization and composition determination.
AB  - Supercritical carbon dioxide (SC-CO(2)) extraction of oil from oak silkworm pupae
      was performed in the present research. Response surface methodology (RSM) was
      applied to optimize the parameters of SC-CO(2) extraction, including extraction
      pressure, temperature, time and CO(2) flow rate on the yield of oak silkworm
      pupal oil (OSPO). The optimal extraction condition for oil yield within the
      experimental range of the variables researched was at 28.03 MPa, 1.83 h, 35.31 
      degrees C and 20.26 L/h as flow rate of CO(2). Under this condition, the oil
      yield was predicted to be 26.18%. The oak silkworm pupal oil contains eight fatty
      acids, and is rich in unsaturated fatty acids and alpha-linolenic acid (ALA),
      accounting for 77.29% and 34.27% in the total oil respectively.

PMID- 22408457
TI  - Epigenetic disregulation in oral cancer.
AB  - Squamous cell carcinoma of the oral region (OSCC) is one of the most common and
      highly aggressive malignancies worldwide, despite the fact that significant
      results have been achieved during the last decades in its detection, prevention
      and treatment. Although many efforts have been made to define the molecular
      signatures that identify the clinical outcome of oral cancers, OSCC still lacks
      reliable prognostic molecular markers. Scientific evidence indicates that
      transition from normal epithelium to pre-malignancy, and finally to oral
      carcinoma, depends on the accumulation of genetic and epigenetic alterations in a
      multistep process. Unlike genetic alterations, epigenetic changes are heritable
      and potentially reversible. The most common examples of such changes are DNA
      methylation, histone modification, and small non-coding RNAs. Although several
      epigenetic changes have been currently linked to OSCC initiation and progression,
      they have been only partially characterized. Over the last decade, it has been
      demonstrated that especially aberrant DNA methylation plays a critical role in
      oral cancer. The major goal of the present paper is to review the recent
      literature about the epigenetic modifications contribution in early and later
      phases of OSCC malignant transformation; in particular we point out the current
      evidence of epigenetic marks as novel markers for early diagnosis and prognosis
      as well as potential therapeutic targets in oral cancer.

PMID- 22408460
TI  - Pyrrolo[3,2-d]pyrimidine derivatives as type II kinase insert domain receptor
      (KDR) inhibitors: CoMFA and CoMSIA studies.
AB  - Kinase insert domain receptor (KDR) inhibitors have been proved to be very
      effective anticancer agents. Molecular docking, 3D-QSAR methods, CoMFA and CoMSIA
      were performed on pyrrolo[3,2-d]pyrimidine derivatives as non-ATP competitive KDR
      inhibitors (type II). The bioactive conformation was explored by docking one
      potent compound 20 into the active site of KDR in its DFG-out inactive
      conformation. The constructed CoMFA and CoMSIA models produced statistically
      significant results with the cross-validated correlation coefficients q(2) of
      0.542 and 0.552, non-cross-validated correlation coefficients r(2) of 0.912 and
      0.955, and predicted correction coefficients r(2) (pred) of 0.913 and 0.897,
      respectively. These results ensure the CoMFA and CoMSIA models as a tool to guide
      the design of a series of new potent KDR inhibitors.

PMID- 22408459
TI  - Impaired iron status in aging research.
AB  - Aging is associated with disturbances in iron metabolism and storage. During the
      last decade, remarkable progress has been made toward understanding their
      cellular and molecular mechanisms in aging and age-associated diseases using both
      cultured cells and animal models. The field has moved beyond descriptive studies
      to potential intervention studies focusing on iron chelation and removal.
      However, some findings remain controversial and inconsistent. This review
      summarizes important features of iron dyshomeostasis in aging research with a
      particular emphasis on current knowledge of the mechanisms underlying age
      associated disorders in rodent models.

PMID- 22408461
TI  - Characterization of different functionalized lipidic nanocapsules as potential
      drug carriers.
AB  - Lipid nanocapsules (LNC) based on a core-shell structure consisting of an oil
      filled core with a surrounding polymer layer are known to be promising vehicles
      for the delivery of hydrophobic drugs in the new therapeutic strategies in anti
      cancer treatments. The present work has been designed as basic research about
      different LNC systems. We have synthesized-and physico-chemically characterized
      three different LNC systems in which the core was constituted by olive oil and
      the shell by different phospholipids (phosphatidyl-serine or lecithin) and other
      biocompatible molecules such as Pluronic((r)) F68 or chitosan. It is notable that
      the olive-oil-phosphatidyl-serine LCN is a novel formulation presented in this
      work and was designed to generate an enriched carboxylic surface. This carboxylic
      layer is meant to link specific antibodies, which could facilitate the specific
      nanocapsule uptake by cancer cells. This is why nanoparticles with phosphatidyl
      serine in their shell have also been used in this work to form immuno
      nanocapsules containing a polyclonal IgG against a model antigen (C-reactive
      protein) covalently bounded by means of a simple and reproducible carbodiimide
      method. An immunological study was made to verify that these IgG-LNC complexes
      showed the expected specific immune response. Finally, a preliminary in vitro
      study was performed by culturing a breast-carcinoma cell line (MCF-7) with Nile
      Red-loaded LNC. We found that these cancer cells take up the fluorescent Nile-
      Red molecule in a process dependent on the surface properties of the
      nanocarriers.

PMID- 22408462
TI  - DNA barcodes of Asian Houbara Bustard (Chlamydotis undulata macqueenii).
AB  - Populations of Houbara Bustards have dramatically declined in recent years.
      Captive breeding and reintroduction programs have had limited success in reviving
      population numbers and thus new technological solutions involving molecular
      methods are essential for the long term survival of this species. In this study,
      we sequenced the 694 bp segment of COI gene of the four specimens of Asian
      Houbara Bustard (Chlamydotis undulata macqueenii). We also compared these
      sequences with earlier published barcodes of 11 individuals comprising different
      families of the orders Gruiformes, Ciconiiformes, Podicipediformes and Crocodylia
      (out group). The pair-wise sequence comparison showed a total of 254 variable
      sites across all the 15 sequences from different taxa. Three of the four
      specimens of Houbara Bustard had an identical sequence of COI gene and one
      individual showed a single nucleotide difference (G > A transition at position
      83). Within the bustard family (Otididae), comparison among the three species
      (Asian Houbara Bustard, Great Bustard (Otis tarda) and the Little Bustard (Tetrax
      tetrax)), representing three different genera, showed 116 variable sites. For
      another family (Rallidae), the intra-family variable sites among the individuals
      of four different genera were found to be 146. The COI genetic distances among
      the 15 individuals varied from 0.000 to 0.431. Phylogenetic analysis using 619 bp
      nucleotide segment of COI clearly discriminated all the species representing
      different genera, families and orders. All the four specimens of Houbara Bustard
      formed a single clade and are clearly separated from other two individuals of the
      same family (Otis tarda and Tetrax tetrax). The nucleotide sequence of partial
      segment of COI gene effectively discriminated the closely related species. This
      is the first study reporting the barcodes of Houbara Bustard and would be helpful
      in future molecular studies, particularly for the conservation of this threatened
      bird in Saudi Arabia.

PMID- 22408463
TI  - Enhancing osteoconduction of PLLA-based nanocomposite scaffolds for bone
      regeneration using different biomimetic signals to MSCs.
AB  - In bone engineering, the adhesion, proliferation and differentiation of
      mesenchymal stromal cells rely on signaling from chemico-physical structure of
      the substrate, therefore prompting the design of mimetic "extracellular matrix"
      like scaffolds. In this study, three-dimensional porous poly-L-lactic acid (PLLA)
      based scaffolds have been mixed with different components, including single
      walled carbon nanotubes (CNT), micro-hydroxyapatite particles (HA), and BMP2, and
      treated with plasma (PT), to obtain four different nanocomposites: PLLA + CNT,
      PLLA + CNTHA, PLLA + CNT + HA + BMP2 and PLLA + CNT + HA + PT. Adult bone marrow
      mesenchymal stromal cells (MSCs) were derived from the femur of orthopaedic
      patients, seeded on the scaffolds and cultured under osteogenic induction up to
      differentiation and mineralization. The release of specific metabolites and
      temporal gene expression profiles of marrow-derived osteoprogenitors were
      analyzed at definite time points, relevant to in vitro culture as well as in vivo
      differentiation. As a result, the role of the different biomimetic components
      added to the PLLA matrix was deciphered, with BMP2-added scaffolds showing the
      highest biomimetic activity on cells differentiating to mature osteoblasts. The
      modification of a polymeric scaffold with reinforcing components which also work
      as biomimetic cues for cells can effectively direct osteoprogenitor cells
      differentiation, so as to shorten the time required for mineralization.

PMID- 22408465
TI  - Antioxidant activity of mulberry fruit extracts.
AB  - Phenolic compounds were extracted from the fruits of Morus nigra and Morus alba
      using methanol and acetone. The sugar-free extracts (SFEs) were prepared using
      Amberlite XAD-16 column chromatography. All of the SFEs exhibited antioxidant
      potential as determined by ABTS (0.75-1.25 mmol Trolox/g), DPPH (2,2-diphenyl-1
      picrylhydrazyl) (EC(50) from 48 MUg/mL to 79 MUg/mL), and reducing power assays.
      However, a stronger activity was noted for the SFEs obtained from Morus nigra
      fruits. These extracts also possessed the highest contents of total phenolics:
      164 mg/g (methanolic SFE) and 173 mg/g (acetonic SFE). The presence of phenolic
      acids and flavonoids in the extracts was confirmed using HPLC method and
      chlorogenic acid and rutin were found as the dominant phenolic constituents in
      the SFEs.

PMID- 22408464
TI  - First insights on organic cosolvent effects on FhuA wildtype and FhuA Delta1-159.
AB  - Circular dichroism (CD) and deconvolution were used to study the structural
      integrity of a "plugged" and an "open" FhuA transmembrane channel protein in the
      presence of varied concentrations of tetrahydrofuran (THF), ethanol (EtOH) and
      chloroform/methanol (C/M). FhuA is an Escherichia coli outer membrane protein
      (78.9 kDa) consisting of 22 beta-sheets and an internal globular cork domain
      which acts as an iron transporter. FhuA and the deletion variant FhuA Delta1-159
      showed comparable and remarkable resistance in the presence of THF (<=40 vol%)
      and EtOH (<=10 vol%). In C/M, significant differences in structural resistance
      were observed (FhuA stable <=10 vol%; FhuA Delta1-159 <=1 vol%). Deconvolution of
      CD-spectra for FhuA and FhuA Delta1-159 yielded beta-sheet contents of 61 %
      (FhuA) and 58% (FhuA Delta1-159). Interestingly, FhuA and FhuA Delta1-159 had
      comparable beta-sheet contents in the presence and absence of all three organic
      cosolvents. Additionally, precipitated FhuA and FhuA Delta1-159 (in 40 vol% C/M
      or 65 vol% THF) redissolved by supplementing the detergent n-octyl-oligo
      oxyethylene (oPOE).

PMID- 22408467
TI  - Spectroscopic parameter and molecular constant investigations on low-lying states
      of BeF radical.
AB  - The potential energy curves (PECs) of X(2)?(+), A(2)Pi(r) and B(2)?(+) states of
      BeF radical have been investigated using the complete active space self
      consistent-field (CASSCF) method, followed by the highly accurate valence
      internally contracted multireference configuration interaction (MRCI) approach at
      the correlation-consistent basis sets, cc-pV5Z for Be and aug-cc-pV6Z for F.
      Based on the PECs of X(2)?(+), A(2)Pi(r) and B(2)?(+) states, the spectroscopic
      parameters (D(e), R(e), omega(e), omega(e)chi(e), alpha(e) and B(e)) have also
      been determined in the present work. With the PECs determined at the present
      level of theory, vibrational states have been predicted for each state when the
      rotational quantum number J equals zero (J = 0). The vibrational levels, inertial
      rotation and centrifugal distortion constants are determined for the three
      states, and the classical turning points are also calculated for the X(2)?(+)
      state. Compared with the available experiments and other theories, it can be seen
      that the present spectroscopic parameter and molecular constant results are more
      fully in agreement with the experimental findings.

PMID- 22408466
TI  - The expression profiling of the lipoxygenase (LOX) family genes during fruit
      development, abiotic stress and hormonal treatments in cucumber (Cucumis sativus
      L.).
AB  - Lipoxygenases (LOXs) are non-haem iron-containing dioxygenases that catalyse
      oxygenation of polyunsaturated fatty acids and lipids to initiate the formation
      of a group of biologically active compounds called oxylipins. Plant oxylipins
      play important and diverse functions in the cells. In the current study,
      expression analysis during cucumber development using semi-quantitative RT-PCR
      revealed that 13 of 23 CsLOX genes were detectable, and were tissue specific or
      preferential accumulation. In total, 12 genes were found to be differentially
      expressed during fruit development and have different patterns of expression in
      exocarp, endocarp and pulp at day 5 after anthesis. The expression analysis of
      these 12 cucumber LOX genes in response to abiotic stresses and plant growth
      regulator treatments revealed their differential transcript in response to more
      than one treatment, indicating their diverse functions in abiotic stress and
      hormone responses. Results suggest that in cucumber the expanded LOX genes may
      play more diverse roles in life cycle and comprehensive data generated will be
      helpful in conducting functional genomic studies to understand their precise
      roles in cucumber fruit development and stress responses.

PMID- 22408468
TI  - Isolation and characterization of new microsatellite markers for the invasive
      softshell clam, Mya arenaria (L.) (Bivalvia: Myidae).
AB  - The invasive softshell clam (Mya arenaria Linnaeus, 1758) is native to the
      northwestern region of the Atlantic Ocean. This species has been introduced in
      the northeast Pacific and along the European coasts, due to intense naval
      transports and aquaculture, and it is now present in all the European seas. In
      this paper we describe seven new microsatellite loci for Mya arenaria. The
      isolated loci are polymorphic with a number of alleles per locus between 6 and
      14. The observed and expected heterozygosities ranged from 0.417 to 0.951, and
      from 0.643 to 0.895, with an average of 0.716 and 0.775, respectively. These
      microsatellite markers should be useful in analyzing this species' genetic
      diversity, which could explain various processes of its invasion history.

PMID- 22408469
TI  - Antiproliferative and proapoptotic activities of methanolic extracts from
      Ligustrum vulgare L. as an individual treatment and in combination with palladium
      complex.
AB  - The aim of this study is to examine the growth inhibitory effects of methanolic
      leaf and fruit extracts of L. vulgare on HCT-116 cells over different time
      periods and their synergistic effect with a Pd(apox) complex. The
      antiproliferative activity of plant extracts alone or in combination with the
      Pd(apox) complex was determined using MTT cell viability assay, where the IC(50)
      value was used as a parameter of cytotoxicity. Results show that
      antiproliferative effects of L. vulgare extracts increase with extension of
      exposure time, with decreasing IC(50) values, except for 72 h where the IC(50)
      values for methanolic leaf extract were lower than for the fruit extract. The
      Pd(apox) complex alone had a weak antiproliferative effect, but combination with
      L. vulgare extracts caused stronger effects with lower IC(50) values than with L.
      vulgare extracts alone. The type of cell death was explored by fluorescence
      microscopy using the acridin orange/ethidium bromide method. Treatments with
      plant extracts caused typical apoptotic morphological changes in HCT-116 cells
      and co-treatments with Pd(apox) complex caused higher levels of apoptotic cells
      than treatment with plant extracts alone. The results indicate that L. vulgare is
      a considerable source of natural bioactive substances with antiproliferative
      activity on HCT-116 cells and which have a substantial synergistic effect with
      the Pd(apox) complex.

PMID- 22408470
TI  - A community-based event delivery protocol in publish/subscribe systems for delay
      tolerant sensor networks.
AB  - The basic operation of a Delay Tolerant Sensor Network (DTSN) is to finish
      pervasive data gathering in networks with intermittent connectivity, while the
      publish/subscribe (Pub/Sub for short) paradigm is used to deliver events from a
      source to interested clients in an asynchronous way. Recently, extension of
      Pub/Sub systems in DTSNs has become a promising research topic. However, due to
      the unique frequent partitioning characteristic of DTSNs, extension of a Pub/Sub
      system in a DTSN is a considerably difficult and challenging problem, and there
      are no good solutions to this problem in published works. To ad apt Pub/Sub
      systems to DTSNs, we propose CED, a community-based event delivery protocol. In
      our design, event delivery is based on several unchanged communities, which are
      formed by sensor nodes in the network according to their connectivity. CED
      consists of two components: event delivery and queue management. In event
      delivery, events in a community are delivered to mobile subscribers once a
      subscriber comes into the community, for improving the data delivery ratio. The
      queue management employs both the event successful delivery time and the event
      survival time to decide whether an event should be delivered or dropped for
      minimizing the transmission overhead. The effectiveness of CED is demonstrated
      through comprehensive simulation studies.

PMID- 22408471
TI  - Fiber loop ringdown - a time-domain sensing technique for multi-function fiber
      optic sensor platforms: current status and design perspectives.
AB  - Fiber loop ringdown (FLRD) utilizes an inexpensive telecommunications light
      source, a photodiode, and a section of single-mode fiber to form a uniform fiber
      optic sensor platform for sensing various quantities, such as pressure,
      temperature, strain, refractive index, chemical species, biological cells, and
      small volume of fluids. In FLRD, optical losses of a light pulse in a fiber loop
      induced by changes in a quantity are measured by the light decay time constants.
      FLRD measures time to detect a quantity; thus, FLRD is referred to as a time
      domain sensing technique. FLRD sensors have near real-time response, multi-pass
      enhanced high-sensitivity, and relatively low cost (i.e., without using an
      optical spectral analyzer). During the last eight years since the introduction of
      the original form of fiber ringdown spectroscopy, there has been increasing
      interest in the FLRD technique in fiber optic sensor developments, and new
      application potential is being explored. This paper first discusses the
      challenging issues in development of multi-function, fiber optic sensors or
      sensor networks using current fiber optic sensor sensing schemes, and then gives
      a review on current fiber optic sensor development using FLRD technique. Finally,
      design perspectives on new generation, multi-function, fiber optic sensor
      platforms using FLRD technique are particularly presented.

PMID- 22408472
TI  - A real-time tool positioning sensor for machine-tools.
AB  - In machining, natural oscillations, and elastic, gravitational or temperature
      deformations, are still a problem to guarantee the quality of fabricated parts.
      In this paper we present an optical measurement system designed to track and
      localize in 3D a reference retro-reflector close to the machine-tool's drill. The
      complete system and its components are described in detail. Several tests, some
      static (including impacts and rotations) and others dynamic (by executing linear
      and circular trajectories), were performed on two different machine tools. It has
      been integrated, for the first time, a laser tracking system into the position
      control loop of a machine-tool. Results indicate that oscillations and
      deformations close to the tool can be estimated with micrometric resolution and a
      bandwidth from 0 to more than 100 Hz. Therefore this sensor opens the possibility
      for on-line compensation of oscillations and deformations.

PMID- 22408473
TI  - Description of a portable wireless device for high-frequency body temperature
      acquisition and analysis.
AB  - We describe a device for dual channel body temperature monitoring. The device can
      operate as a real time monitor or as a data logger, and has Bluetooth
      capabilities to enable for wireless data download to the computer used for data
      analysis. The proposed device is capable of sampling temperature at a rate of 1
      sample per minute with a resolution of 0.01  degrees C . The internal memory
      allows for stand-alone data logging of up to 10 days. The device has a battery
      life of 50 hours in continuous real-time mode. In addition to describing the
      proposed device in detail, we report the results of a statistical analysis
      conducted to assess its accuracy and reproducibility.

PMID- 22408474
TI  - Connectivity, coverage and placement in wireless sensor networks.
AB  - Wireless communication between sensors allows the formation of flexible sensor
      networks, which can be deployed rapidly over wide or inaccessible areas. However,
      the need to gather data from all sensors in the network imposes constraints on
      the distances between sensors. This survey describes the state of the art in
      techniques for determining the minimum density and optimal locations of relay
      nodes and ordinary sensors to ensure connectivity, subject to various degrees of
      uncertainty in the locations of the nodes.

PMID- 22408475
TI  - A portable luminometer with a disposable electrochemiluminescent biosensor for
      lactate determination.
AB  - A hand-held luminometer for measuring electrochemiluminescence (ECL) for lactate
      determination and based on one-shot biosensors fabricated using screen-printed
      electrodes is described. The lactate recognition system is based on lactate
      oxidase and the transduction system consists of electro-oxidation of luminol,
      with all the reagents immobilized in a Methocel membrane. The membrane
      composition and reaction conditions have been optimized to obtain adequate
      sensitivity. The luminometer is based on a large silicon photodiode as detector
      and includes a programmable potentiostat to initialize the chemical reaction and
      signal processing circuitry, designed to acquire a low level photocurrent with
      offset cancelation, low pass filtering for noise attenuation and adjustable gain
      up to 10(12) V/A. The one-shot biosensor responds to lactate rapidly, with an
      acquisition time of 2.5 min, obtaining a linear dependence from 8 * 10(-6) to 2 *
      10(-4) M, a detection limit of 2.4 * 10(-6) M and a sensor-to-sensor
      reproducibility (relative standard deviation, RSD) of around 7-10 % at the medium
      level of the range.

PMID- 22408476
TI  - Delay QoS and MAC Aware Energy-Efficient Data-Aggregation Routing in Wireless
      Sensor Networks.
AB  - By eliminating redundant data flows, data aggregation capabilities in wireless
      sensor networks could transmit less data to reduce the total energy consumption.
      However, additional data collisions incur extra data retransmissions. These data
      retransmissions not only increase the system energy consumption, but also
      increase link transmission delays. The decision of when and where to aggregate
      data depends on the trade-off between data aggregation and data retransmission.
      The challenges of this problem need to address the routing (layer 3) and the MAC
      layer retransmissions (layer 2) at the same time to identify energy-efficient
      data-aggregation routing assignments, and in the meantime to meet the delay QoS.
      In this paper, for the first time, we study this cross-layer design problem by
      using optimization-based heuristics. We first model this problem as a non-convex
      mathematical programming problem where the objective is to minimize the total
      energy consumption subject to the data aggregation tree and the delay QoS
      constraints. The objective function includes the energy in the transmission mode
      (data transmissions and data retransmissions) and the energy in the idle mode (to
      wait for data from downstream nodes in the data aggregation tree). The proposed
      solution approach is based on Lagrangean relaxation in conjunction with a number
      of optimization-based heuristics. From the computational experiments, it is shown
      that the proposed algorithm outperforms existing heuristics that do not take MAC
      layer retransmissions and the energy consumption in the idle mode into account.

PMID- 22408477
TI  - Structure and sensor properties of thin ordered solid films.
AB  - Miniaturized gas sensors and biosensors based on nanostructured sensing elements
      have attracted considerable interest because these nanostructured materials can
      be used to significantly improve sensor sensitivity and the response time. We
      report here on a generic, reversible sensing platform based on hybrid nanofilms.
      Thin ordered Langmuir-Blodgett (LB) films built of fluorene derivatives were used
      as effective gas sensors for both oxidative and reductive analytes. A novel
      immobilization method based on thin LB films as a matrix has been developed for
      construction of sensing protein layers. Biomolecules can often be incorporated
      into and immobilized on Langmuir-Blodgett films using adsorption methods or by
      covalent immobilization of proteins. The sensor sensitisation was achieved by an
      amphiphilic N-alkyl-bis(thiophene)arylenes admixed into the film. The interlaced
      derivative was expected to facilitate the electron transfer, thereby enhancing
      the sensor sensitivity. The results suggest that this may be very promising
      approach for exploring the interactions between proteins and high throughput
      detection of phenol derivatives in wastewater.

PMID- 22408478
TI  - Defect Detection in Arc-Welding Processes by Means of the Line-to-Continuum
      Method and Feature Selection.
AB  - Plasma optical spectroscopy is widely employed in on-line welding diagnostics.
      The determination of the plasma electron temperature, which is typically selected
      as the output monitoring parameter, implies the identification of the atomic
      emission lines. As a consequence, additional processing stages are required with
      a direct impact on the real time performance of the technique. The line-to
      continuum method is a feasible alternative spectroscopic approach and it is
      particularly interesting in terms of its computational efficiency. However, the
      monitoring signal highly depends on the chosen emission line. In this paper, a
      feature selection methodology is proposed to solve the uncertainty regarding the
      selection of the optimum spectral band, which allows the employment of the line
      to-continuum method for on-line welding diagnostics. Field test results have been
      conducted to demonstrate the feasibility of the solution.

PMID- 22408479
TI  - Advances in multi-sensor data fusion: algorithms and applications.
AB  - With the development of satellite and remote sensing techniques, more and more
      image data from airborne/satellite sensors have become available. Multi-sensor
      image fusion seeks to combine information from different images to obtain more
      inferences than can be derived from a single sensor. In image-based application
      fields, image fusion has emerged as a promising research area since the end of
      the last century. The paper presents an overview of recent advances in multi
      sensor satellite image fusion. Firstly, the most popular existing fusion
      algorithms are introduced, with emphasis on their recent improvements. Advances
      in main applications fields in remote sensing, including object identification,
      classification, change detection and maneuvering targets tracking, are described.
      Both advantages and limitations of those applications are then discussed.
      Recommendations are addressed, including: (1) Improvements of fusion algorithms;
      (2) Development of "algorithm fusion" methods; (3) Establishment of an automatic
      quality assessment scheme.

PMID- 22408480
TI  - Resonant Magnetic Field Sensors Based On MEMS Technology.
AB  - Microelectromechanical systems (MEMS) technology allows the integration of
      magnetic field sensors with electronic components, which presents important
      advantages such as small size, light weight, minimum power consumption, low cost,
      better sensitivity and high resolution. We present a discussion and review of
      resonant magnetic field sensors based on MEMS technology. In practice, these
      sensors exploit the Lorentz force in order to detect external magnetic fields
      through the displacement of resonant structures, which are measured with optical,
      capacitive, and piezoresistive sensing techniques. From these, the optical
      sensing presents immunity to electromagnetic interference (EMI) and reduces the
      read-out electronic complexity. Moreover, piezoresistive sensing requires an easy
      fabrication process as well as a standard packaging. A description of the
      operation mechanisms, advantages and drawbacks of each sensor is considered. MEMS
      magnetic field sensors are a potential alternative for numerous applications,
      including the automotive industry, military, medical, telecommunications,
      oceanographic, spatial, and environment science. In addition, future markets will
      need the development of several sensors on a single chip for measuring different
      parameters such as the magnetic field, pressure, temperature and acceleration.

PMID- 22408481
TI  - Investigation of SOI Raman Lasers for Mid-Infrared Gas Sensing.
AB  - In this paper, the investigation and detailed modeling of a cascaded Raman laser,
      operating in the midwave infrared region, is described. The device is based on
      silicon-on-insulator optical waveguides and a coupled resonant microcavity.
      Theoretical results are compared with recent experiments, demonstrating a very
      good agreement. Design criteria are derived for cascaded Raman lasers working as
      continuous wave light sources to simultaneously sense two types of gases, namely
      C(2)H(6) and CO(2), at a moderate power level of 130 mW.

PMID- 22408482
TI  - Optimization of TiO(2) and PMAPTAC Concentrations of a Chemical Humidity Sensing
      Mechanism.
AB  - This work aims to achieve an optimization of the TiO(2) and PMAPTAC
      concentrations in a chemical resistive-type humidity sensing mechanism (RHSM).
      Our idea is based primarily on the modeling of the sensing mechanism. This model
      takes into account the parameters of non-linearity, hysteresis, temperature,
      frequency, substrate type. Furthermore, we investigated the TiO(2) and PMAPTAC
      effects concentrations on the humidity sensing properties in our model. Secondly,
      we used the Matlab environment to create a database for an ideal model for the
      sensing mechanism, where the response of this ideal model is linear for any value
      of the above parameters. We have done the training to create an analytical model
      for the sensing mechanism (SM) and the ideal model (IM). After that, the SM and
      IM models are established on PSPICE simulator, where the output of the first is
      identical to the output of the RHSM used and the output of the last is the ideal
      response. Finally a "DIF bloc" was realized to make the difference between the SM
      output and the IM output, where this difference represents the linearity error,
      we take the minimum error, to identify the optimal TiO(2) and PMAPTAC
      concentrations. However, a compromise between concentrations, humidity and
      temperature must be performed. The simulation results show that in low humidity
      and at temperature more than 25  degrees C, sample 1 is the best (in alumina
      substrate). However, the sample 9 represents the best sensor (in PET substrate)
      predominately for the lowest humidity and temperature.

PMID- 22408483
TI  - Integration of an on-axis general sun-tracking formula in the algorithm of an
      open-loop sun-tracking system.
AB  - A novel on-axis general sun-tracking formula has been integrated in the algorithm
      of an open-loop sun-tracking system in order to track the sun accurately and cost
      effectively. Sun-tracking errors due to installation defects of the 25 m(2)
      prototype solar concentrator have been analyzed from recorded solar images with
      the use of a CCD camera. With the recorded data, misaligned angles from ideal
      azimuth-elevation axes have been determined and corrected by a straightforward
      changing of the parameters' values in the general formula of the tracking
      algorithm to improve the tracking accuracy to 2.99 mrad, which falls below the
      encoder resolution limit of 4.13 mrad.

PMID- 22408484
TI  - Synthesis methods, microscopy characterization and device integration of
      nanoscale metal oxide semiconductors for gas sensing.
AB  - A comparison is made between SnO(2), ZnO, and TiO(2) single-crystal nanowires and
      SnO(2) polycrystalline nanofibers for gas sensing. Both nanostructures possess a
      one-dimensional morphology. Different synthesis methods are used to produce these
      materials: thermal evaporation-condensation (TEC), controlled oxidation, and
      electrospinning. Advantages and limitations of each technique are listed.
      Practical issues associated with harvesting, purification, and integration of
      these materials into sensing devices are detailed. For comparison to the nascent
      form, these sensing materials are surface coated with Pd and Pt nanoparticles.
      Gas sensing tests, with respect to H(2), are conducted at ambient and elevated
      temperatures. Comparative normalized responses and time constants for the
      catalyst and noncatalyst systems provide a basis for identification of the
      superior metal-oxide nanostructure and catalyst combination. With temperature
      dependent data, Arrhenius analyses are made to determine activation energies for
      the catalyst-assisted systems.

PMID- 22408485
TI  - Determination of diclofenac on a dysprosium nanowire- modified carbon paste
      electrode accomplished in a flow injection system by advanced filtering.
AB  - A new detection technique called Fast Fourier Transform Square-Wave Voltammetry
      (FFT SWV) is based on measurements of electrode admittance as a function of
      potential. The response of the detector (microelectrode), which is generated by a
      redox processes, is fast, which makes the method suitable for most applications
      involving flowing electrolytes. The carbon paste electrode was modified by
      nanostructures to improve sensitivity. Synthesized dysprosium nanowires provide a
      more effective nanotube-like surface [1-4] so they are good candidates for use as
      a modifier for electrochemical reactions. The redox properties of diclofenac were
      used for its determination in human serum and urine samples. The support
      electrolyte that provided a more defined and intense peak current for diclofenac
      determination was a 0.05 mol L(-1) acetate buffer pH = 4.0. The drug presented an
      irreversible oxidation peak at 850 mV vs. Ag/AgCl on a modified nanowire carbon
      paste electrode which produced high current and reduced the oxidation potential
      by about 100 mV. Furthermore, the signal-to-noise ratio was significantly
      increased by application of a discrete Fast Fourier Transform (FFT) method,
      background subtraction and two-dimensional integration of the electrode response
      over a selected potential range and time window. To obtain the much sensivity the
      effective parameters such as frequency, amplitude and pH was optimized. As a
      result, C(DL) of 2.0 * 10(-9) M and an LOQ of 5.0 * 10(-9) M were found for the
      determination for diclofenac. A good recovery was obtained for assay spiked urine
      samples and a good quantification of diclofenac was achieved in a commercial
      formulation.

PMID- 22408486
TI  - Magnetic Field Sensors Based on Giant Magnetoresistance (GMR) Technology:
      Applications in Electrical Current Sensing.
AB  - The 2007 Nobel Prize in Physics can be understood as a global recognition to the
      rapid development of the Giant Magnetoresistance (GMR), from both the physics and
      engineering points of view. Behind the utilization of GMR structures as read
      heads for massive storage magnetic hard disks, important applications as solid
      state magnetic sensors have emerged. Low cost, compatibility with standard CMOS
      technologies and high sensitivity are common advantages of these sensors. This
      way, they have been successfully applied in a lot different environments. In this
      work, we are trying to collect the Spanish contributions to the progress of the
      research related to the GMR based sensors covering, among other subjects, the
      applications, the sensor design, the modelling and the electronic interfaces,
      focusing on electrical current sensing applications.

PMID- 22408487
TI  - Vehicle Signal Analysis Using Artificial Neural Networks for a Bridge Weigh-in
      Motion System.
AB  - This paper describes the procedures for development of signal analysis algorithms
      using artificial neural networks for Bridge Weigh-in-Motion (B-WIM) systems.
      Through the analysis procedure, the extraction of information concerning heavy
      traffic vehicles such as weight, speed, and number of axles from the time domain
      strain data of the B-WIM system was attempted. As one of the several possible
      pattern recognition techniques, an Artificial Neural Network (ANN) was employed
      since it could effectively include dynamic effects and bridge-vehicle
      interactions. A number of vehicle traveling experiments with sufficient load
      cases were executed on two different types of bridges, a simply supported pre
      stressed concrete girder bridge and a cable-stayed bridge. Different types of WIM
      systems such as high-speed WIM or low-speed WIM were also utilized during the
      experiments for cross-checking and to validate the performance of the developed
      algorithms.

PMID- 22408489
TI  - Micro sensor node for air pollutant monitoring: hardware and software issues.
AB  - Wireless sensor networks equipped with various gas sensors have been actively
      used for air quality monitoring. Previous studies have typically explored system
      issues that include middleware or networking performance, but most research has
      barely considered the details of the hardware and software of the sensor node
      itself. In this paper, we focus on the design and implementation of a sensor
      board for air pollutant monitoring applications. Several hardware and software
      issues are discussed to explore the possibilities of a practical WSN-based air
      pollution monitoring system. Through extensive experiments and evaluation, we
      have determined the various characteristics of the gas sensors and their
      practical implications for air pollutant monitoring systems.

PMID- 22408488
TI  - A label-free electronic biosensor for detection of bone turnover markers.
AB  - This paper describes the development of a biosensor based on label-free
      immunosensing for the detection of the C-terminal telopeptide bone turnover
      marker from type-1 collagen. A self-assembled monolayer (SAM) of
      dithiodipropionic acid was deposited on a gold electrode. Then streptavidin and
      biotinylated anti-human C-terminal telopeptide antibody were successively
      conjugated on the self-assembled monolayer. Electrochemical impedance
      measurements were made to characterize each step of the
      SAM/streptavidin/biotinylated antibody binding. Subsequently, electrochemical
      impedance was measured with different concentrations of C-teminal telopeptide. A
      detection limit of 50 ng/mL and a dynamic range up to 3 MUg/mL were achieved. To
      our knowledge, this is the first attempt to develop a label-free immunosensor
      based on electrochemical impedance with DC bias for detection of bone-related
      degradation and rebuilding products. The electronic biosensor might eventually be
      used for quantitative point-of-care screening of bone health. It is hoped that
      analysis of bone turnover markers can indicate the beginning of bone diseases
      such as osteoarthritis and osteoporosis so that treatment might start early when
      it is most effective.

PMID- 22408490
TI  - A Coupled Field Multiphysics Modeling Approach to Investigate RF MEMS Switch
      Failure Modes under Various Operational Conditions.
AB  - In this paper, the reliability of capacitive shunt RF MEMS switches have been
      investigated using three dimensional (3D) coupled multiphysics finite element
      (FE) analysis. The coupled field analysis involved three consecutive multiphysics
      interactions. The first interaction is characterized as a two-way sequential
      electromagnetic (EM)-thermal field coupling. The second interaction represented a
      one-way sequential thermal-structural field coupling. The third interaction
      portrayed a two-way sequential structural-electrostatic field coupling. An
      automated substructuring algorithm was utilized to reduce the computational cost
      of the complicated coupled multiphysics FE analysis. The results of the
      substructured FE model with coupled field analysis is shown to be in good
      agreement with the outcome of previously published experimental and numerical
      studies. The current numerical results indicate that the pull-in voltage and the
      buckling temperature of the RF switch are functions of the microfabrication
      residual stress state, the switch operational frequency and the surrounding
      packaging temperature. Furthermore, the current results point out that by
      introducing proper mechanical approaches such as corrugated switches and through
      holes in the switch membrane, it is possible to achieve reliable pull-in
      voltages, at various operating temperatures. The performed analysis also shows
      that by controlling the mean and gradient residual stresses, generated during
      microfabrication, in conjunction with the proposed mechanical approaches, the
      power handling capability of RF MEMS switches can be increased, at a wide range
      of operational frequencies. These design features of RF MEMS switches are of
      particular importance in applications where a high RF power (frequencies above 10
      GHz) and large temperature variations are expected, such as in satellites and
      airplane condition monitoring.

PMID- 22408491
TI  - Collaborative distributed scheduling approaches for wireless sensor network.
AB  - Energy constraints restrict the lifetime of wireless sensor networks (WSNs) with
      battery-powered nodes, which poses great challenges for their large scale
      application. In this paper, we propose a family of collaborative distributed
      scheduling approaches (CDSAs) based on the Markov process to reduce the energy
      consumption of a WSN. The family of CDSAs comprises of two approaches: a one-step
      collaborative distributed approach and a two-step collaborative distributed
      approach. The approaches enable nodes to learn the behavior information of its
      environment collaboratively and integrate sleep scheduling with transmission
      scheduling to reduce the energy consumption. We analyze the adaptability and
      practicality features of the CDSAs. The simulation results show that the two
      proposed approaches can effectively reduce nodes' energy consumption. Some other
      characteristics of the CDSAs like buffer occupation and packet delay are also
      analyzed in this paper. We evaluate CDSAs extensively on a 15-node WSN testbed.
      The test results show that the CDSAs conserve the energy effectively and are
      feasible for real WSNs.

PMID- 22408492
TI  - Fabrication of Poly(p-Phenylene)/Zeolite Composites and Their Responses Towards
      Ammonia.
AB  - Poly(p-phenylene) (PPP) was chemically synthesized via oxidative polymerization
      using benzene and doped with FeCl(3). The electrical conductivity response of the
      doped PPP (dPPP) towards CO, H(2) and NH(3) is investigated. dPPP shows no
      electrical conductivity response towards the first two gases (CO and H(2)), but
      it shows a definite negative response towards NH(3). The electrical conductivity
      sensitivity of dPPP increases linearly with increasing NH(3) concentration. To
      improve the sensitivity of the sensor towards NH(3), ZSM-5 zeolite is added into
      the conductive polymer matrix. The electrical sensitivity of the sensor increases
      with increasing zeolite content up to 30%. The effect of the type of cation in
      the zeolite pores is investigated: namely, Na(+), K(+), NH(4) (+) and H(+). The
      electrical conductivity sensitivity of the composites with different cations in
      the zeolite can be arranged in this order: K(+) < no zeolite < Na(+) < NH(4) (+)
      < H(+). The variation in electrical sensitivity with cation type can be described
      in terms of the acid-base interaction, the zeolite pore size and surface area.
      The PPP/Zeolite composite with H(+) possesses the highest electrical sensitivity
      of -0.36 since H(+) has the highest acidity, the highest pore volume and surface
      area, which combine to induce a more favorable NH(3) adsorption and interaction
      with the conductive polymer.

PMID- 22408493
TI  - A radio-aware routing algorithm for reliable directed diffusion in lossy wireless
      sensor networks.
AB  - In Wireless Sensor Networks (WSNs), transmission errors occur frequently due to
      node failure, battery discharge, contention or interference by objects. Although
      Directed Diffusion has been considered as a prominent data-centric routing
      algorithm, it has some weaknesses due to unexpected network errors. In order to
      address these problems, we proposed a radio-aware routing algorithm to improve
      the reliability of Directed Diffusion in lossy WSNs. The proposed algorithm is
      aware of the network status based on the radio information from MAC and PHY
      layers using a cross-layer design. The cross-layer design can be used to get
      detailed information about current status of wireless network such as a link
      quality or transmission errors of communication links. The radio information
      indicating variant network conditions and link quality was used to determine an
      alternative route that provides reliable data transmission under lossy WSNs.
      According to the simulation result, the radio-aware reliable routing algorithm
      showed better performance in both grid and random topologies with various error
      rates. The proposed solution suggested the possibility of providing a reliable
      transmission method for QoS requests in lossy WSNs based on the radio-awareness.
      The energy and mobility issues will be addressed in the future work.

PMID- 22408494
TI  - Identification of tea storage times by linear discrimination analysis and back
      propagation neural network techniques based on the eigenvalues of principal
      components analysis of e-nose sensor signals.
AB  - An electronic nose (E-nose) was employed to detect the aroma of green tea after
      different storage times. Longjing green tea dry leaves, beverages and residues
      were detected with an E-nose, respectively. In order to decrease the data
      dimensionality and optimize the feature vector, the E-nose sensor response data
      were analyzed by principal components analysis (PCA) and the five main principal
      components values were extracted as the input for the discrimination analysis.
      The storage time (0, 60, 120, 180 and 240 days) was better discriminated by
      linear discrimination analysis (LDA) and was predicted by the back-propagation
      neural network (BPNN) method. The results showed that the discrimination and
      testing results based on the tea leaves were better than those based on tea
      beverages and tea residues. The mean errors of the tea leaf data were 9, 2.73,
      3.93, 6.33 and 6.8 days, respectively.

PMID- 22408495
TI  - Efficient aggregation of multiple classes of information in wireless sensor
      networks.
AB  - Congestion in a Wireless Sensor Network (WSN) can lead to buffer overflow,
      resource waste and delay or loss of critical information from the sensors. In
      this paper, we propose the Priority-based Coverage-aware Congestion Control (PCC)
      algorithm which is distributed, priority-distinct, and fair. PCC provides higher
      priority to packets with event information in which the sink is more interested.
      PCC employs a queue scheduler that can selectively drop any packet in the queue.
      PCC gives fair chance to all sensors to send packets to the sink, irrespective of
      their specific locations, and therefore enhances the coverage fidelity of the
      WSN. Based on a detailed simulation analysis, we show that PCC can efficiently
      relieve congestion and significantly improve the system performance based on
      multiple metrics such as event throughput and coverage fidelity. We generalize
      PCC to address data collection in a WSN in which the sensor nodes have multiple
      sensing devices and can generate multiple types of information. We propose a
      Pricing System that can under congestion effectively collect different types of
      data generated by the sensor nodes according to values that are placed on
      different information by the sink. Simulation analysis show that our Pricing
      System can achieve higher event throughput for packets with higher priority and
      achieve fairness among different categories. Moreover, given a fixed system
      capacity, our proposed Pricing System can collect more information of the type
      valued by the sink.

PMID- 22408496
TI  - Neural network emulation of the integral equation model with multiple scattering.
AB  - The Integral Equation Model with multiple scattering (IEMM) represents a well
      established method that provides a theoretical framework for the scattering of
      electromagnetic waves from rough surfaces. A critical aspect is the long
      computational time required to run such a complex model. To deal with this
      problem, a neural network technique is proposed in this work. In particular, we
      have adopted neural networks to reproduce the backscattering coefficients
      predicted by IEMM at L- and C-bands, thus making reference to presently operative
      satellite radar sensors, i.e., that aboard ERS-2, ASAR on board ENVISAT (C-band),
      and PALSAR aboard ALOS (L-band). The neural network-based model has been designed
      for radar observations of both flat and tilted surfaces, in order to make it
      applicable for hilly terrains too. The assessment of the proposed approach has
      been carried out by comparing neural network-derived backscattering coefficients
      with IEMM-derived ones. Different databases with respect to those employed to
      train the networks have been used for this purpose. The outcomes seem to prove
      the feasibility of relying on a neural network approach to efficiently and
      reliably approximate an electromagnetic model of surface scattering.

PMID- 22408497
TI  - Guest Editor's Concluding Remarks-Advances in Usage of ANN, Discussion of an
      Unsolved Problem, and Some Differences between Papers Written by Engineers and by
      Physicians.

PMID- 22408498
TI  - Magnetic nanoparticle sensors.
AB  - Many types of biosensors employ magnetic nanoparticles (diameter = 5-300 nm) or
      magnetic particles (diameter = 300-5,000 nm) which have been surface
      functionalized to recognize specific molecular targets. Here we cover three types
      of biosensors that employ different biosensing principles, magnetic materials,
      and instrumentation. The first type consists of magnetic relaxation switch assay
      sensors, which are based on the effects magnetic particles exert on water proton
      relaxation rates. The second type consists of magnetic particle relaxation
      sensors, which determine the relaxation of the magnetic moment within the
      magnetic particle. The third type is magnetoresistive sensors, which detect the
      presence of magnetic particles on the surface of electronic devices that are
      sensitive to changes in magnetic fields on their surface. Recent improvements in
      the design of magnetic nanoparticles (and magnetic particles), together with
      improvements in instrumentation, suggest that magnetic material-based biosensors
      may become widely used in the future.

PMID- 22408499
TI  - Biomimetic Yeast Cell Typing-Application of QCMs.
AB  - Artificial antibodies represent a key factor in the generation of sensing systems
      for the selective detection of bioanalytes of variable sizes. With biomimetic
      surfaces, the important model organism Saccharomyces cerevisiae and several of
      its growth stages may be detected. Quartz crystal microbalances (QCM) with 10 MHz
      fundamental frequency and coated with polymers imprinted with synchronized yeast
      cells are presented, which are able to detect duplex cells with high selectivity.
      Furthermore, a multichannel quartz crystal microbalance (MQCM) was designed and
      optimized for the measurement in liquids. This one-chip system based on four
      electrode geometry allows the simultaneous detection of four analytes and, thus,
      provides a monitoring system for biotechnology and process control. For further
      standardization of the method, synthetic stamps containing plastic yeast cells in
      different growth stages were produced and utilized for imprinting. Mass-sensitive
      measurements with such MIPs resulted in the same sensor characteristics as
      obtained for those imprinted with native yeast cells.

PMID- 22408500
TI  - Semiconducting metal oxide based sensors for selective gas pollutant detection.
AB  - A review of some papers published in the last fifty years that focus on the
      semiconducting metal oxide (SMO) based sensors for the selective and sensitive
      detection of various environmental pollutants is presented.

PMID- 22408501
TI  - A distributed sensor network for the control of a bioclimatic house in Spain.
AB  - The XXI century home should be a digital habitat, a connected residence, but at
      the same time it should be involved in sustainability and the environment. The
      location of new technologies at home, and its acceptance by the user, requires,
      among other actions, a significant diffusion and activity to be undertaken. This
      work proposes the development of a Smart House network designed for its
      integration into a sustainable and bioclimatic solar house. The paper focuses on
      a specific aspect of the house design, the control system bus, developed for the
      management of the different parameters, variables, sensors and actuators which
      coexist at home. Finally, the system has been installed in a laboratory
      bioclimatic house. Environmental variable experiments based on the control of
      passive elements, such as phase shift gels, are presented. Experimental results
      show that the system is able to benefit from the bioclimatic elements in the
      house by taking into account the user preferences.

PMID- 22408502
TI  - Sensor Calibration Based on Incoherent Optical Fiber Bundles (IOFB) Used For
      Remote Image Transmission.
AB  - Image transmission using incoherent optical fiber bundles (IOFB) requires prior
      calibration to obtain the spatial in-out fiber correspondence in order to
      reconstruct the image captured by the pseudo-sensor. This information is recorded
      in a Look-Up Table (LUT), used later for reordering the fiber positions and
      reconstructing the original image. This paper presents a method based on line
      scan to obtain the in-out correspondence. The results demonstrate that this
      technique yields a remarkable reduction in processing time and increased image
      quality by introducing a fiber detection algorithm, an intensity compensation
      process and finally, a single interpolation algorithm.

PMID- 22408504
TI  - Major improvements of quartz crystal pulling sensitivity and linearity using
      series reactance.
AB  - This paper presents a new method of substantially improving frequency pullability
      and linearity using reactance in series with an AT fundamental crystal operated
      with a series load capacitance in the range of 3 to 50 pF and frequencies in the
      range of 3.5 to 21 MHz. The research describes high quartz pullability and
      linearity by varying the load capacitance. The paper also gives impedance
      circuits for crystal unit (3.5 MHz) together with load capacitance and
      compensation reactance. The experimental results show that the new approach using
      compensation method of quartz crystal connected in series reactance increases the
      frequency pulling range by *25 to *100 depending on the type of oscillator and
      compensation factor "k" in the temperature range of 10 to 40  degrees C.

PMID- 22408503
TI  - Breath analysis using laser spectroscopic techniques: breath biomarkers, spectral
      fingerprints, and detection limits.
AB  - Breath analysis, a promising new field of medicine and medical instrumentation,
      potentially offers noninvasive, real-time, and point-of-care (POC) disease
      diagnostics and metabolic status monitoring. Numerous breath biomarkers have been
      detected and quantified so far by using the GC-MS technique. Recent advances in
      laser spectroscopic techniques and laser sources have driven breath analysis to
      new heights, moving from laboratory research to commercial reality. Laser
      spectroscopic detection techniques not only have high-sensitivity and high
      selectivity, as equivalently offered by the MS-based techniques, but also have
      the advantageous features of near real-time response, low instrument costs, and
      POC function. Of the approximately 35 established breath biomarkers, such as
      acetone, ammonia, carbon dioxide, ethane, methane, and nitric oxide, 14 species
      in exhaled human breath have been analyzed by high-sensitivity laser
      spectroscopic techniques, namely, tunable diode laser absorption spectroscopy
      (TDLAS), cavity ringdown spectroscopy (CRDS), integrated cavity output
      spectroscopy (ICOS), cavity enhanced absorption spectroscopy (CEAS), cavity leak
      out spectroscopy (CALOS), photoacoustic spectroscopy (PAS), quartz-enhanced
      photoacoustic spectroscopy (QEPAS), and optical frequency comb cavity-enhanced
      absorption spectroscopy (OFC-CEAS). Spectral fingerprints of the measured
      biomarkers span from the UV to the mid-IR spectral regions and the detection
      limits achieved by the laser techniques range from parts per million to parts per
      billion levels. Sensors using the laser spectroscopic techniques for a few breath
      biomarkers, e.g., carbon dioxide, nitric oxide, etc. are commercially available.
      This review presents an update on the latest developments in laser-based breath
      analysis.

PMID- 22408505
TI  - Fluorescence enhancement of fluorescein isothiocyanate-labeled protein a caused
      by affinity binding with immunoglobulin g in bovine plasma.
AB  - Fluorescence enhancement of fluorescein isothiocyanate-labeled protein A (FITC
      protein A) caused by the binding with immunoglobulin G (IgG) in bovine plasma was
      studied. FITC-protein A was immobilized onto a glass surface by covalent bonds.
      An increase in fluorescence intensity was dependent on IgG concentration ranging
      from 20 to 78 MUg/mL in both phosphate buffer saline and bovine plasma. This
      method requires no separation procedure, and the reaction time is less than 15
      min. A fluorescence enhancement assay by the affinity binding of fluorescence
      labeled reagent is thus available for the rapid determination of biomolecules in
      plasma.

PMID- 22408506
TI  - Cross-layer active predictive congestion control protocol for wireless sensor
      networks.
AB  - In wireless sensor networks (WSNs), there are numerous factors that may cause
      network congestion problems, such as the many-to-one communication modes, mutual
      interference of wireless links, dynamic changes of network topology and the
      memory-restrained characteristics of nodes. All these factors result in a network
      being more vulnerable to congestion. In this paper, a cross-layer active
      predictive congestion control scheme (CL-APCC) for improving the performance of
      networks is proposed. Queuing theory is applied in the CL-APCC to analyze data
      flows of a single-node according to its memory status, combined with the analysis
      of the average occupied memory size of local networks. It also analyzes the
      current data change trends of local networks to forecast and actively adjust the
      sending rate of the node in the next period. In order to ensure the fairness and
      timeliness of the network, the IEEE 802.11 protocol is revised based on waiting
      time, the number of the node's neighbors and the original priority of data
      packets, which dynamically adjusts the sending priority of the node. The
      performance of CL-APCC, which is evaluated by extensive simulation experiments.
      is more efficient in solving the congestion in WSNs. Furthermore, it is clear
      that the proposed scheme has an outstanding advantage in terms of improving the
      fairness and lifetime of networks.

PMID- 22408507
TI  - Turbidimeter design and analysis: a review on optical fiber sensors for the
      measurement of water turbidity.
AB  - Turbidimeters operate based on the optical phenomena that occur when incident
      light through water body is scattered by the existence of foreign particles which
      are suspended within it. This review paper elaborates on the standards and
      factors that may influence the measurement of turbidity. The discussion also
      focuses on the optical fiber sensor technologies that have been applied within
      the lab and field environment and have been implemented in the measurement of
      water turbidity and concentration of particles. This paper also discusses and
      compares results from three different turbidimeter designs that use various
      optical components. Mohd Zubir and Bashah and Daraigan have introduced a design
      which has simple configurations. Omar and MatJafri, on the other hand, have
      established a new turbidimeter design that makes use of optical fiber cable as
      the light transferring medium. The application of fiber optic cable to the
      turbidimeter will present a flexible measurement technique, allowing measurements
      to be made online. Scattered light measurement through optical fiber cable
      requires a highly sensitive detector to interpret the scattered light signal.
      This has made the optical fiber system have higher sensitivity in measuring
      turbidity compared to the other two simple turbidimeters presented in this paper.
      Fiber optic sensors provide the potential for increased sensitivity over large
      concentration ranges. However, many challenges must be examined to develop
      sensors that can collect reliable turbidity measurements in situ.

PMID- 22408508
TI  - A CMOS-Compatible, Low-Noise ISFET Based on High Efficiency Ion-Modulated Lateral
      Bipolar Conduction.
AB  - Ion-sensitive, field-effect transistors (ISFET) have been useful biosensors in
      many applications. However, the signal-to-noise ratio of the ISFET is limited by
      its intrinsic, low-frequency noise. This paper presents an ISFET capable of
      utilizing lateral-bipolar conduction to reduce low-frequency noise. With a
      particular layout design, the conduction efficiency is further enhanced.
      Moreover, the ISFET is compatible with the standard CMOS technology. All
      materials above the gate-oxide are removed by simple, die-level post-CMOS
      process, allowing ions to modulate the lateral-bipolar current directly. By
      varying the gate-to-bulk voltage, the operation mode of the ISFET is controlled
      effectively, so is the noise performance measured and compared. Finally, the
      biasing conditions preferable for different low-noise applications are
      identified. Under the identified biasing condition, the signal-to-noise ratio of
      the ISFET as a pH sensor is proved to be improved by more than five times.

PMID- 22408509
TI  - Temperature effects and compensation-control methods.
AB  - In the analysis of the effects of temperature on the performance of
      microgyroscopes, it is found that the resonant frequency of the microgyroscope
      decreases linearly as the temperature increases, and the quality factor changes
      drastically at low temperatures. Moreover, the zero bias changes greatly with
      temperature variations. To reduce the temperature effects on the microgyroscope,
      temperature compensation-control methods are proposed. In the first place, a BP
      (Back Propagation) neural network and polynomial fitting are utilized for
      building the temperature model of the microgyroscope. Considering the simplicity
      and real-time requirements, piecewise polynomial fitting is applied in the
      temperature compensation system. Then, an integral-separated PID (Proportion
      Integration Differentiation) control algorithm is adopted in the temperature
      control system, which can stabilize the temperature inside the microgyrocope in
      pursuing its optimal performance. Experimental results reveal that the
      combination of microgyroscope temperature compensation and control methods is
      both realizable and effective in a miniaturized microgyroscope prototype.

PMID- 22408510
TI  - Arrays of regenerated fiber bragg gratings in non-hydrogen-loaded photosensitive
      fibers for high-temperature sensor networks.
AB  - We report about the possibility of using regenerated fiber Bragg gratings
      generated in photosensitive fibers without applying hydrogen loading for high
      temperature sensor networks. We use a thermally induced regenerative process
      which leads to a secondary increase in grating reflectivity. This refractive
      index modification has shown to become more stable after the regeneration up to
      temperatures of 600  degrees C. With the use of an interferometric writing
      technique, it is possible also to generate arrays of regenerated fiber Bragg
      gratings for sensor networks.

PMID- 22408511
TI  - Magneto-optical relaxation measurements of functionalized nanoparticles as a
      novel biosensor.
AB  - Measurements of magneto-optical relaxation signals of magnetic nanoparticles
      functionalized with biomolecules are a novel biosensing tool. Upon transmission
      of a laser beam through a nanoparticle suspension in a pulsed magnetic field, the
      properties of the laser beam change. This can be detected by optical methods.
      Biomolecular binding events leading to aggregation of nanoparticles are
      ascertainable by calculating the relaxation time and from this, the hydrodynamic
      diameters of the involved particles from the optical signal. Interaction between
      insulin-like growth factor 1 (IGF-1) and its antibody was utilized for
      demonstration of the measurement setup applicability as an immunoassay.
      Furthermore, a formerly developed kinetic model was utilized in order to
      determine kinetic parameters of the interaction. Beside utilization of the method
      as an immunoassay it can be applied for the characterization of diverse magnetic
      nanoparticles regarding their size and size distribution.

PMID- 22408512
TI  - Nanomaterials - acetylcholinesterase enzyme matrices for organophosphorus
      pesticides electrochemical sensors: a review.
AB  - Acetylcholinesterase (AChE) is an important cholinesterase enzyme present in the
      synaptic clefts of living organisms. It maintains the levels of the
      neurotransmitter acetylcholine by catalyzing the hydrolysis reaction of
      acetylcholine to thiocholine. This catalytic activity of AChE is drastically
      inhibited by trace amounts of organophosphorus (OP) pesticides present in the
      environment. As a result, effective monitoring of OP pesticides in the
      environment is very desirable and has been done successfully in recent years with
      the use of nanomaterial-based AChE sensors. In such sensors, the enzyme AChE has
      been immobilized onto nanomaterials like multiwalled carbon nanotubes, gold
      nanoparticles, zirconia nanoparticles, cadmium sulphide nano particles or quantum
      dots. These nanomaterial matrices promote significant enhancements of OP
      pesticide determinations, with the thiocholine oxidation occurring at much lower
      oxidation potentials. Moreover, nanomaterial-based AChE sensors with rapid
      response, increased operational and long storage stability are extremely well
      suited for OP pesticide determination over a wide concentration range. In this
      review, the unique advantages of using nanomaterials as AChE immobilization
      matrices are discussed. Further, detection limits, sensitivities and correlation
      coefficients obtained using various electroanalytical techniques have also been
      compared with chromatographic techniques.

PMID- 22408513
TI  - The "Wireless Sensor Networks for City-Wide Ambient Intelligence (WISE-WAI)"
      Project.
AB  - This paper gives a detailed technical overview of some of the activities carried
      out in the context of the "Wireless Sensor networks for city-Wide Ambient
      Intelligence (WISE-WAI)" project, funded by the Cassa di Risparmio di Padova e
      Rovigo Foundation, Italy. The main aim of the project is to demonstrate the
      feasibility of large-scale wireless sensor network deployments, whereby tiny
      objects integrating one or more environmental sensors (humidity, temperature,
      light intensity), a microcontroller and a wireless transceiver are deployed over
      a large area, which in this case involves the buildings of the Department of
      Information Engineering at the University of Padova. We will describe how the
      network is organized to provide full-scale automated functions, and which
      services and applications it is configured to provide. These applications include
      long-term environmental monitoring, alarm event detection and propagation, single
      sensor interrogation, localization and tracking of objects, assisted navigation,
      as well as fast data dissemination services to be used, e.g., to rapidly re
      program all sensors over-the-air. The organization of such a large testbed
      requires notable efforts in terms of communication protocols and strategies,
      whose design must pursue scalability, energy efficiency (while sensors are
      connected through USB cables for logging and debugging purposes, most of them
      will be battery-operated), as well as the capability to support applications with
      diverse requirements. These efforts, the description of a subset of the results
      obtained so far, and of the final objectives to be met are the scope of the
      present paper.

PMID- 22408514
TI  - A distributed geo-routing algorithm for wireless sensor networks.
AB  - Geographic wireless sensor networks use position information for greedy routing.
      Greedy routing works well in dense networks, whereas in sparse networks it may
      fail and require a recovery algorithm. Recovery algorithms help the packet to get
      out of the communication void. However, these algorithms are generally costly for
      resource constrained position-based wireless sensor networks (WSNs). In this
      paper, we propose a void avoidance algorithm (VAA), a novel idea based on
      upgrading virtual distance. VAA allows wireless sensor nodes to remove all stuck
      nodes by transforming the routing graph and forwarding packets using only greedy
      routing. In VAA, the stuck node upgrades distance unless it finds a next hop node
      that is closer to the destination than it is. VAA guarantees packet delivery if
      there is a topologically valid path. Further, it is completely distributed,
      immediately responds to node failure or topology changes and does not require
      planarization of the network. NS-2 is used to evaluate the performance and
      correctness of VAA and we compare its performance to other protocols. Simulations
      show our proposed algorithm consumes less energy, has an efficient path and
      substantially less control overheads.

PMID- 22408515
TI  - Synthesis of the system modeling and signal detecting circuit of a novel vacuum
      microelectronic accelerometer.
AB  - A novel high-precision vacuum microelectronic accelerometer has been successfully
      fabricated and tested in our laboratory. This accelerometer has unique advantages
      of high sensitivity, fast response, and anti-radiation stability. It is a
      prototype intended for navigation applications and is required to feature micro-g
      resolution. This paper briefly describes the structure and working principle of
      our vacuum microelectronic accelerometer, and the mathematical model is also
      established. The performances of the accelerometer system are discussed after
      Matlab modeling. The results show that, the dynamic response of the accelerometer
      system is significantly improved by choosing appropriate parameters of signal
      detecting circuit, and the signal detecting circuit is designed. In order to
      attain good linearity and performance, the closed-loop control mode is adopted.
      Weak current detection technology is studied, and integral T-style feedback
      network is used in I/V conversion, which will eliminate high-frequency noise at
      the front of the circuit. According to the modeling parameters, the low-pass
      filter is designed. This circuit is simple, reliable, and has high precision.
      Experiments are done and the results show that the vacuum microelectronic
      accelerometer exhibits good linearity over -1 g to +1 g, an output sensitivity of
      543 mV/g, and a nonlinearity of 0.94 %.

PMID- 22408516
TI  - A portable and autonomous magnetic detection platform for biosensing.
AB  - This paper presents a prototype of a platform for biomolecular recognition
      detection. The system is based on a magnetoresistive biochip that performs
      biorecognition assays by detecting magnetically tagged targets. All the
      electronic circuitry for addressing, driving and reading out signals from spin
      valve or magnetic tunnel junctions sensors is implemented using off-the-shelf
      components. Taking advantage of digital signal processing techniques, the
      acquired signals are processed in real time and transmitted to a digital analyzer
      that enables the user to control and follow the experiment through a graphical
      user interface. The developed platform is portable and capable of operating
      autonomously for nearly eight hours. Experimental results show that the noise
      level of the described platform is one order of magnitude lower than the one
      presented by the previously used measurement set-up. Experimental results also
      show that this device is able to detect magnetic nanoparticles with a diameter of
      250 nm at a concentration of about 40 fM. Finally, the biomolecular recognition
      detection capabilities of the platform are demonstrated by performing a
      hybridization assay using complementary and non-complementary probes and a
      magnetically tagged 20mer single stranded DNA target.

PMID- 22408517
TI  - Design and Fabrication of a MEMS Flow Sensor and Its Application in Precise
      Liquid Dispensing.
AB  - A high speed MEMS flow sensor to enhance the reliability and accuracy of a liquid
      dispensing system is proposed. Benefitting from the sensor information feedback,
      the system can self-adjust the open time of the solenoid valve to accurately
      dispense desired volumes of reagent without any pre-calibration. First, an
      integrated high-speed liquid flow sensor based on the measurement of the pressure
      difference across a flow channel is presented. Dimensions of the micro-flow
      channel and two pressure sensors have been appropriately designed to meet the
      static and dynamic requirements of the liquid dispensing system. Experiments
      results show that the full scale (FS) flow measurement ranges up to 80 MUL/s,
      with a nonlinearity better than 0.51% FS. Secondly, a novel closed-loop control
      strategy is proposed to calculate the valve open time in each dispensing cycle,
      which makes the system immune to liquid viscosity, pressure fluctuation, and
      other sources of error. Finally, dispensing results show that the system can
      achieve better dispensing performance, and the coefficient of variance (CV) for
      liquid dispensing is below 3% at 1 MUL and below 4% at 100 nL.

PMID- 22408518
TI  - Global oxygen detection in water using luminescent probe on anodized aluminum.
AB  - We have developed anodized-aluminum pressure-sensitive paint (AA-PSP) as a global
      oxygen sensor in water. Platinum (II) meso-tetra(pentafluorophenyl)porphine is
      selected as a luminophore based on a dipping deposition study. The developed AA
      PSP is characterized using water calibration setup by controlling dissolved
      oxygen concentration. It is shown that AA-PSP yields 4.0% change in luminescence
      per 1 mg/L of oxygen concentration at 23 degrees C. Other characteristics, such
      as temperature dependency, photo-degradation, and physical stability, are
      discussed in this paper. This AA-PSP is used to demonstrate its capability of
      global oxygen detection in water using the impingement of oxygen rich water (20
      mg/L). Even though the difference in water is only the concentration of oxygen,
      we can obtain global oxygen information of the jet impingement using a fast frame
      rate camera. Oxygen maps as well as cross-sectional distributions are shown every
      0.1 s.

PMID- 22408519
TI  - Fluorescence Detection and Discrimination of ss- and ds-DNA with a Water Soluble
      Oligopyrene Derivative.
AB  - A novel water-soluble cationic conjugated oligopyrene derivative,
      oligo(N(1),N(1),N(1),N(4),N(4),N(4)-hexamethyl-2-(4-(pyren-1-yl) butane-1,4
      diaminium bromide) (OHPBDB), was synthesized by a combination of chemical and
      electrochemical synthesis techniques. Each oligomer chain has five pyrene
      derivative repeating units and brings 10 positive charges. OHPBDB showed high and
      rapid fluorescence quenching in aqueous media upon addition of trace amounts of
      single-stranded (ss) and double-stranded (ds) DNA. The Stern-Volmer constants for
      ss- and ds-DNA were measured to be as high as 1.3 * 10(8) mol(-1).L and 1.2 *
      10(8) mol(-1).L, respectively. On the other hand, distinct fluorescence
      enhancement of OHPBDB upon addition of large amount of ss-DNA or ds-DNA was
      observed. Furthermore, ss-DNA showed much stronger fluorescence enhancement than
      that of ds-DNA, thus yielding a clear and simple signal useful for the
      discrimination between ss- and ds-DNA in aqueous media.

PMID- 22408520
TI  - Metric Potential of a 3D Measurement System Based on Digital Compact Cameras.
AB  - This paper presents an optical measuring system based on low cost, high
      resolution digital cameras. Once the cameras are synchronised, the portable and
      adjustable system can be used to observe living beings, bodies in motion, or
      deformations of very different sizes. Each of the cameras has been modelled
      individually and studied with regard to the photogrammetric potential of the
      system. We have investigated the photogrammetric precision obtained from the
      crossing of rays, the repeatability of results, and the accuracy of the
      coordinates obtained. Systematic and random errors are identified in validity
      assessment of the definition of the precision of the system from crossing of rays
      or from marking residuals in images. The results have clearly demonstrated the
      capability of a low-cost multiple-camera system to measure with sub-millimetre
      precision.

PMID- 22408521
TI  - Design and evaluation of a wireless sensor network based aircraft strength
      testing system.
AB  - The verification of aerospace structures, including full-scale fatigue and static
      test programs, is essential for structure strength design and evaluation.
      However, the current overall ground strength testing systems employ a large
      number of wires for communication among sensors and data acquisition facilities.
      The centralized data processing makes test programs lack efficiency and
      intelligence. Wireless sensor network (WSN) technology might be expected to
      address the limitations of cable-based aeronautical ground testing systems. This
      paper presents a wireless sensor network based aircraft strength testing (AST)
      system design and its evaluation on a real aircraft specimen. In this paper, a
      miniature, high-precision, and shock-proof wireless sensor node is designed for
      multi-channel strain gauge signal conditioning and monitoring. A cluster-star
      network topology protocol and application layer interface are designed in detail.
      To verify the functionality of the designed wireless sensor network for strength
      testing capability, a multi-point WSN based AST system is developed for static
      testing of a real aircraft undercarriage. Based on the designed wireless sensor
      nodes, the wireless sensor network is deployed to gather, process, and transmit
      strain gauge signals and monitor results under different static test loads. This
      paper shows the efficiency of the wireless sensor network based AST system,
      compared to a conventional AST system.

PMID- 22408522
TI  - RoPEUS: A New Robust Algorithm for Static Positioning in Ultrasonic Systems.
AB  - A well known problem for precise positioning in real environments is the presence
      of outliers in the measurement sample. Its importance is even bigger in
      ultrasound based systems since this technology needs a direct line of sight
      between emitters and receivers. Standard techniques for outlier detection in
      range based systems do not usually employ robust algorithms, failing when
      multiple outliers are present. The direct application of standard robust
      regression algorithms fails in static positioning (where only the current
      measurement sample is considered) in real ultrasound based systems mainly due to
      the limited number of measurements and the geometry effects. This paper presents
      a new robust algorithm, called RoPEUS, based on MM estimation, that follows a
      typical two-step strategy: 1) a high breakdown point algorithm to obtain a clean
      sample, and 2) a refinement algorithm to increase the accuracy of the solution.
      The main modifications proposed to the standard MM robust algorithm are a built
      in check of partial solutions in the first step (rejecting bad geometries) and
      the off-line calculation of the scale of the measurements. The algorithm is
      tested with real samples obtained with the 3D-LOCUS ultrasound localization
      system in an ideal environment without obstacles. These measurements are
      corrupted with typical outlying patterns to numerically evaluate the algorithm
      performance with respect to the standard parity space algorithm. The algorithm
      proves to be robust under single or multiple outliers, providing similar accuracy
      figures in all cases.

PMID- 22408523
TI  - Analysis of the Emitted Wavelet of High-Resolution Bowtie GPR Antennas.
AB  - Most Ground Penetrating Radars (GPR) cover a wide frequency range by emitting
      very short time wavelets. In this work, we study in detail the wavelet emitted by
      two bowtie GPR antennas with nominal frequencies of 800 MHz and 1 GHz. Knowledge
      of this emitted wavelet allows us to extract as much information as possible from
      recorded signals, using advanced processing techniques and computer simulations.
      Following previously published methodology used by Rial et al. [1], which ensures
      system stability and reliability in data acquisition, a thorough analysis of the
      wavelet in both time and frequency domain is performed. Most of tests were
      carried out with air as propagation medium, allowing a proper analysis of the
      geometrical attenuation factor. Furthermore, we attempt to determine, for each
      antenna, a time zero in the records to allow us to correctly assign a position to
      the reflectors detected by the radar. Obtained results indicate that the time
      zero is not a constant value for the evaluated antennas, but instead depends on
      the characteristics of the material in contact with the antenna.

PMID- 22408524
TI  - Extended averaged learning subspace method for hyperspectral data classification.
AB  - Averaged learning subspace methods (ALSM) have the advantage of being easily
      implemented and appear to outperform in classification problems of hyperspectral
      images. However, there remain some open and challenging problems, which if
      addressed, could further improve their performance in terms of classification
      accuracy. We carried out experiments mainly by using two kinds of improved
      subspace methods (namely, dynamic and fixed subspace methods), in conjunction
      with the [0,1] and [-1,+1] normalization methods. We used different performance
      indicators to support our experimental studies: classification accuracy,
      computation time, and the stability of the parameter settings. Results are
      presented for the AVIRIS Indian Pines data set. Experimental analysis showed that
      the fixed subspace method combined with the [0,1] normalization method yielded
      higher classification accuracy than other subspace methods. Moreover, ALSMs are
      easily applied: only two parameters need to be set, and they can be applied
      directly to hyperspectral data. In addition, they can completely identify
      training samples in a finite number of iterations.

PMID- 22408526
TI  - Coronatine Gene Expression In Vitro and In Planta, and Protein Accumulation
      During Temperature Downshift in Pseudomonas syringae.
AB  - The plant pathogenic bacterium Pseudomonas syringae PG4180 synthesizes high
      levels of the phytotoxin coronatine (COR) at the virulence-promoting temperature
      of 18  degrees C, but negligible amounts at 28  degrees C. Temperature-dependent
      COR gene expression is regulated by a modified two-component system, consisting
      of a response regulator, CorR, the histidine protein kinase CorS, and a third
      component, termed CorP. We analyzed at transcriptional and translational levels
      the expression of corS and the cma operon involved in COR biosynthesis after a
      temperature downshift from 28 to 18  degrees C. Expression of cma was induced
      within 20 min and increased steadily whereas corS expression was only slightly
      temperature-dependent. Accumulation of CmaB correlated with accumulation of cma
      mRNA. However, cma transcription was suppressed by inhibition of de novo protein
      biosynthesis. A transcriptional fusion of the cma promoter to a promoterless egfp
      gene was used to monitor the cma expression in vitro and in planta. A steady
      induction of cma::egfp by temperature downshift was observed in both
      environments. The results indicate that PG4180 responds to a temperature decrease
      with COR gene expression. However, COR gene expression and protein biosynthesis
      increased steadily, possibly reflecting adaptation to long-term rather than rapid
      temperature changes.

PMID- 22408527
TI  - An Overview of the Use of the SimSphere Soil Vegetation Atmosphere Transfer
      (SVAT) Model for the Study of Land-Atmosphere Interactions.
AB  - Soil Vegetation Atmosphere Transfer (SVAT) models consist of deterministic
      mathematical representations of the physical processes involved between the land
      surface and the atmosphere and of their interactions, at time-steps acceptable
      for the study of land surface processes. The present article provides a
      comprehensive and systematic review of one such SVAT model suitable for use in
      mesoscale or boundary layer studies, originally developed by [1]. This model,
      which has evolved significantly both architecturally and functionally since its
      foundation, has been widely applied in over thirty interdisciplinary science
      investigations, and it is currently used as a learning resource for students in a
      number of educational institutes globally. The present review is also regarded as
      very timely, since a variation of a method using this specific SVAT model along
      with satellite observations is currently being considered in a scheme being
      developed for the operational retrieval of soil surface moisture by the US
      National Polar-orbiting Operational Environmental Satellite System (NPOESS), in a
      series of satellites that are due to be launched from 2016 onwards.

PMID- 22408528
TI  - Development of membrane selective electrode for determination of the
      antipsychotic sulpiride in pharmaceuticals and urine.
AB  - The construction and electrochemical response characteristics of a poly(vinyl
      chloride) (PVC) membrane selective electrode for the determination of sulpiride
      (SPD) are described. The sensing membrane comprised an ion-exchanger formed
      between the protonated drug and tetraphenylborate (TPB(-)) in a plasticized PVC
      matrix. The influence of membrane composition on the electrode response was
      studied. The electrode showed a fast, stable and Nernstian response over a
      sulpiride concentration range (1 * 10(-4) - 1 * 10(-2) M) with a mean slope of
      58.4 +/- 0.9 mV dec(-1) of concentration, a mean detection limit of 4.2 * 10(-5)
      +/- 1.2 * 10(-5) M, a wide working pH range (2 - 8) and a fast response time (<
      15 s). The electrode showed good selectivity towards sulpiride with respect to
      some inorganic and organic compounds. When the electrode was applied to the
      determination of sulpiride in pharmaceuticals and human urine, a high percentage
      of recovery was attained with no need for sample pretreatment procedures because
      of the lack of interfering matrix effects.

PMID- 22408529
TI  - Solid state gas sensor research in Germany - a status report.
AB  - This status report overviews activities of the German gas sensor research
      community. It highlights recent progress in the field of potentiometric,
      amperometric, conductometric, impedimetric, and field effect-based gas sensors.
      It is shown that besides step-by-step improvements of conventional principles,
      e.g. by the application of novel materials, novel principles turned out to enable
      new markets. In the field of mixed potential gas sensors, novel materials allow
      for selective detection of combustion exhaust components. The same goal can be
      reached by using zeolites for impedimetric gas sensors. Operando spectroscopy is
      a powerful tool to learn about the mechanisms in n-type and in p-type
      conductometric sensors and to design knowledge-based improved sensor devices.
      Novel deposition methods are applied to gain direct access to the material
      morphology as well as to obtain dense thick metal oxide films without high
      temperature steps. Since conductometric and impedimetric sensors have the
      disadvantage that a current has to pass the gas sensitive film, film morphology,
      electrode materials, and geometrical issues affect the sensor signal. Therefore,
      one tries to measure directly the Fermi level position either by measuring the
      gas-dependent Seebeck coefficient at high temperatures or at room temperature by
      applying a modified miniaturized Kelvin probe method, where surface adsorption
      based work function changes drive the drain-source current of a field effect
      transistor.

PMID- 22408530
TI  - Standard CMOS Fabrication of a Sensitive Fully Depleted Electrolyte-Insulator
      Semiconductor Field Effect Transistor for Biosensor Applications.
AB  - Microfabricated semiconductor devices are becoming increasingly relevant for
      detection of biological and chemical components. The integration of active
      biological materials together with sensitive transducers offers the possibility
      of generating highly sensitive, specific, selective and reliable biosensors. This
      paper presents the fabrication of a sensitive, fully depleted (FD), electrolyte
      insulator-semiconductor field-effect transistor (EISFET) made with a silicon-on
      insulator (SOI) wafer of a thin 10-30 nm active SOI layer. Initial results are
      presented for device operation in solutions and for bio-sensing. Here we report
      the first step towards a high volume manufacturing of a CMOS-based biosensor that
      will enable various types of applications including medical and environmental
      sensing.

PMID- 22408531
TI  - Modeling of Aerosol Vertical Profiles Using GIS and Remote Sensing.
AB  - The use of Geographic Information Systems (GIS) and Remote Sensing (RS) by
      climatologists, environmentalists and urban planners for three dimensional
      modeling and visualization of the landscape is well established. However no
      previous study has implemented these techniques for 3D modeling of atmospheric
      aerosols because air quality data is traditionally measured at ground points, or
      from satellite images, with no vertical dimension. This study presents a
      prototype for modeling and visualizing aerosol vertical profiles over a 3D urban
      landscape in Hong Kong. The method uses a newly developed technique for the
      derivation of aerosol vertical profiles from AERONET sunphotometer measurements
      and surface visibility data, and links these to a 3D urban model. This permits
      automated modeling and visualization of aerosol concentrations at different
      atmospheric levels over the urban landscape in near-real time. Since the GIS
      platform permits presentation of the aerosol vertical distribution in 3D, it can
      be related to the built environment of the city. Examples are given of the
      applications of the model, including diagnosis of the relative contribution of
      vehicle emissions to pollution levels in the city, based on increased near
      surface concentrations around weekday rush-hour times. The ability to model
      changes in air quality and visibility from ground level to the top of tall
      buildings is also demonstrated, and this has implications for energy use and
      environmental policies for the tall mega-cities of the future.

PMID- 22408532
TI  - The use of flow-injection analysis with chemiluminescence detection of aqueous
      ferrous iron in waters containing high concentrations of organic compounds.
AB  - An evaluation of flow-injection analysis with chemiluminescence detection (FIA
      CL) to quantify Fe(2+) ((aq)) in freshwaters was performed. Iron-coordinating
      and/or iron-reducing compounds, dissolved organic matter (DOM), and samples from
      two natural water systems were used to amend standard solutions of Fe(2+) ((aq)).
      Slopes of the response curves from ferrous iron standards (1 - 100 nM) were
      compared to the response curves of iron standards containing the amendments.
      Results suggest that FIA-CL is not suitable for systems containing ascorbate,
      hydroxylamine, cysteine or DOM. Little or no change in sensitivity occurred in
      solutions of oxalate and glycine or in natural waters with little organic matter.

PMID- 22408534
TI  - Underwater acoustic sensors based on fiber bragg gratings.
AB  - We report on recent results obtained with a fiber optic hydrophone based on the
      intensity modulation of the laser light in a FBG (Fiber Bragg Grating) under the
      influence of the sound pressure. In order to control the behavior of the
      hydrophone in terms of sensitivity and bandwidth, FBGs have been coated with
      proper materials, characterized by different elastic modulus and shapes. In
      particular, new experiments have been carried out using a cylindrical geometry
      with two different coating, showing that the sensitivity is not influenced by the
      shape but by the transversal dimension and the material characteristics of the
      coating.

PMID- 22408535
TI  - A High Isolation Series-Shunt RF MEMS Switch.
AB  - This paper presents a wide band compact high isolation microelectromechanical
      systems (MEMS) switch implemented on a coplanar waveguide (CPW) with three ohmic
      switch cells, which is based on the series-shunt switch design. The ohmic switch
      shows a low intrinsic loss of 0.1 dB and an isolation of 24.8 dB at 6 GHz. The
      measured average pull-in voltage is 28 V and switching time is 47 MUs. In order
      to shorten design period of the high isolation switch, a structure-based small
      signal model for the 3-port ohmic MEMS switch is developed and parameters are
      extracted from the measured results. Then a high isolation switch has been
      developed where each 3-port ohmic MEMS switch is closely located. The agreement
      of the measured and modeled radio frequency (RF) performance demonstrates the
      validity of the electrical equivalent model. Measurements of the series-shunt
      switch indicate an outstanding isolation of more than 40 dB and a low insertion
      loss of 0.35 dB from DC to 12 GHz with total chip size of 1 mm * 1.2 mm.

PMID- 22408533
TI  - Antibody-based sensors: principles, problems and potential for detection of
      pathogens and associated toxins.
AB  - Antibody-based sensors permit the rapid and sensitive analysis of a range of
      pathogens and associated toxins. A critical assessment of the implementation of
      such formats is provided, with reference to their principles, problems and
      potential for 'on-site' analysis. Particular emphasis is placed on the detection
      of foodborne bacterial pathogens, such as Escherichia coli and Listeria
      monocytogenes, and additional examples relating to the monitoring of fungal
      pathogens, viruses, mycotoxins, marine toxins and parasites are also provided.

PMID- 22408536
TI  - SITHON: A Wireless Network of in Situ Optical Cameras Applied to the Early
      Detection-Notification-Monitoring of Forest Fires.
AB  - The SITHON system, a fully wireless optical imaging system, integrating a network
      of in-situ optical cameras linking to a multi-layer GIS database operated by
      Control Operating Centres, has been developed in response to the need for early
      detection, notification and monitoring of forest fires. This article presents in
      detail the architecture and the components of SITHON, and demonstrates the first
      encouraging results of an experimental test with small controlled fires over
      Sithonia Peninsula in Northern Greece. The system has already been scheduled to
      be installed in some fire prone areas of Greece.

PMID- 22408538
TI  - Multi-Aperture CMOS Sun Sensor for Microsatellite Attitude Determination.
AB  - This paper describes the high precision digital sun sensor under development at
      the University of Naples. The sensor determines the sun line orientation in the
      sensor frame from the measurement of the sun position on the focal plane. It
      exploits CMOS technology and an original optical head design with multiple
      apertures. This allows simultaneous multiple acquisitions of the sun as spots on
      the focal plane. The sensor can be operated either with a fixed or a variable
      number of sun spots, depending on the required field of view and sun-line
      measurement precision. Multiple acquisitions are averaged by using techniques
      which minimize the computational load to extract the sun line orientation with
      high precision. Accuracy and computational efficiency are also improved thanks to
      an original design of the calibration function relying on neural networks.
      Extensive test campaigns are carried out using a laboratory test facility
      reproducing sun spectrum, apparent size and distance, and variable illumination
      directions. Test results validate the sensor concept, confirming the precision
      improvement achievable with multiple apertures, and sensor operation with a
      variable number of sun spots. Specifically, the sensor provides accuracy and
      precision in the order of 1 arcmin and 1 arcsec, respectively.

PMID- 22408537
TI  - An overview of recent strategies in pathogen sensing.
AB  - Pathogenic bacteria are one of the major concerns in food industries and water
      treatment facilities because of their rapid growth and deleterious effects on
      human health. The development of fast and accurate detection and identification
      systems for bacterial strains has long been an important issue to researchers.
      Although confirmative for the identification of bacteria, conventional methods
      require time-consuming process involving either the test of characteristic
      metabolites or cellular reproductive cycles. In this paper, we review recent
      sensing strategies based on micro- and nano-fabrication technology. These
      technologies allow for a great improvement of detection limit, therefore, reduce
      the time required for sample preparation. The paper will be focused on newly
      developed nano- and micro-scaled biosensors, novel sensing modalities utilizing
      microfluidic lab-on-a-chip, and array technology for the detection of pathogenic
      bacteria.

PMID- 22408539
TI  - Building facade reconstruction by fusing terrestrial laser points and images.
AB  - Laser data and optical data have a complementary nature for three dimensional
      feature extraction. Efficient integration of the two data sources will lead to a
      more reliable and automated extraction of three dimensional features. This paper
      presents a semiautomatic building facade reconstruction approach, which
      efficiently combines information from terrestrial laser point clouds and close
      range images. A building facade's general structure is discovered and established
      using the planar features from laser data. Then strong lines in images are
      extracted using Canny extractor and Hough transformation, and compared with
      current model edges for necessary improvement. Finally, textures with optimal
      visibility are selected and applied according to accurate image orientations.
      Solutions to several challenge problems throughout the collaborated
      reconstruction, such as referencing between laser points and multiple images and
      automated texturing, are described. The limitations and remaining works of this
      approach are also discussed.

PMID- 22408540
TI  - Optimal Detection Range of RFID Tag for RFID-based Positioning System Using the k
      NN Algorithm.
AB  - Positioning technology to track a moving object is an important and essential
      component of ubiquitous computing environments and applications. An RFID-based
      positioning system using the k-nearest neighbor (k-NN) algorithm can determine
      the position of a moving reader from observed reference data. In this study, the
      optimal detection range of an RFID-based positioning system was determined on the
      principle that tag spacing can be derived from the detection range. It was
      assumed that reference tags without signal strength information are regularly
      distributed in 1-, 2- and 3-dimensional spaces. The optimal detection range was
      determined, through analytical and numerical approaches, to be 125% of the tag
      spacing distance in 1-dimensional space. Through numerical approaches, the range
      was 134% in 2-dimensional space, 143% in 3-dimensional space.

PMID- 22408541
TI  - Characterization of Long-period Grating Refractive Index Sensors and Their
      Applications.
AB  - The influence of grating length and bend radius of long-period gratings (LPGs) on
      refractive index sensing was examined. Sensitivity to refractive indexes smaller
      than that of silica could be enhanced by bending LPGs. Bent LPGs lost sensitivity
      to refractive indexes higher than that of silica, whereas a 20-mm-long LPG
      arranged in a straight line had considerable sensitivity. These experimental
      results demonstrated that the sensitivity characteristics of LPGs to refractive
      index could be controlled by grating length and bend radius.

PMID- 22408542
TI  - 3D Vision by Using Calibration Pattern with Inertial Sensor and RBF Neural
      Networks.
AB  - Camera calibration is a crucial prerequisite for the retrieval of metric
      information from images. The problem of camera calibration is the computation of
      camera intrinsic parameters (i.e., coefficients of geometric distortions,
      principle distance and principle point) and extrinsic parameters (i.e., 3D
      spatial orientations: omega, phi, kappa, and 3D spatial translations: t(x), t(y),
      t(z)). The intrinsic camera calibration (i.e., interior orientation) models the
      imaging system of camera optics, while the extrinsic camera calibration (i.e.,
      exterior orientation) indicates the translation and the orientation of the camera
      with respect to the global coordinate system. Traditional camera calibration
      techniques require a predefined mathematical-camera model and they use prior
      knowledge of many parameters. Definition of a realistic camera model is quite
      difficult and computation of camera calibration parameters are error-prone. In
      this paper, a novel implicit camera calibration method based on Radial Basis
      Functions Neural Networks is proposed. The proposed method requires neither an
      exactly defined camera model nor any prior knowledge about the imaging-setup or
      classical camera calibration parameters. The proposed method uses a calibration
      grid-pattern rotated around a static-fixed axis. The rotations of the calibration
      grid-pattern have been acquired by using an Xsens MTi-9 inertial sensor and in
      order to evaluate the success of the proposed method, 3D reconstruction
      performance of the proposed method has been compared with the performance of a
      traditional camera calibration method, Modified Direct Linear Transformation
      (MDLT). Extensive simulation results show that the proposed method achieves a
      better performance than MDLT aspect of 3D reconstruction.

PMID- 22408543
TI  - Development of a prototype miniature silicon microgyroscope.
AB  - A miniature vacuum-packaged silicon microgyroscope (SMG) with symmetrical and
      decoupled structure was designed to prevent unintended coupling between drive and
      sense modes. To ensure high resonant stability and strong disturbance resisting
      capacity, a self-oscillating closed-loop circuit including an automatic gain
      control (AGC) loop based on electrostatic force feedback is adopted in drive
      mode, while, dual-channel decomposition and reconstruction closed loops are
      applied in sense mode. Moreover, the temperature effect on its zero bias was
      characterized experimentally and a practical compensation method is given. The
      testing results demonstrate that the useful signal and quadrature signal will not
      interact with each other because their phases are decoupled. Under a scale factor
      condition of 9.6 mV/( degrees )/s, in full measurement range of +/- 300 deg/s,
      the zero bias stability reaches 15( degrees )/h with worse-case nonlinearity of
      400 ppm, and the temperature variation trend of the SMG bias is thus largely
      eliminated, so that the maximum bias value is reduced to one tenth of the
      original after compensation from -40 ( degrees )C to 80 ( degrees )C.

PMID- 22408544
TI  - Exact Weighted-FBP Algorithm for Three-Orthogonal-Circular Scanning
      Reconstruction.
AB  - Recently, 3D image fusion reconstruction using a FDK algorithm along three
      orthogonal circular isocentric orbits has been proposed. On the other hand, we
      know that 3D image reconstruction based on three-orthogonal circular isocentric
      orbits is sufficient in the sense of Tuy data sufficiency condition. Therefore
      the datum obtained from three-orthogonal circular isocentric orbits can derive an
      exact reconstruction algorithm. In this paper, an exact weighted-FBP algorithm
      with three-orthogonal circular isocentric orbits is derived by means of
      Katsevich's equations of filtering lines based on a circle trajectory and a
      modified weighted form of Tuy's reconstruction scheme.

PMID- 22408545
TI  - A new and inexpensive pyranometer for the visible spectral range.
AB  - This paper presents the design, construction and testing of a new photodiode
      based pyranometer for the visible spectral range (approx. 400 to 750 nm), whose
      principal characteristics are: accuracy, ease of connection, immunity to noise,
      remote programming and operation, interior temperature regulation, cosine error
      minimisation and all this at a very low cost, tens of times lower than that of
      commercial thermopile-based devices. This new photodiode-based pyranometer
      overcomes traditional problems in this type of device and offers similar
      characteristics to those of thermopile-based pyranometers and, therefore, can be
      used in any installation where reliable measurement of solar irradiance is
      necessary, especially in those where cost is a deciding factor in the choice of a
      meter. This new pyranometer has been registered in the Spanish Patent and
      Trademark Office under the number P200703162.

PMID- 22408546
TI  - Immobilization of HRP in Mesoporous Silica and Its Application for the
      Construction of Polyaniline Modified Hydrogen Peroxide Biosensor.
AB  - Polyaniline (PANI), an attractive conductive polymer, has been successfully
      applied in fabricating various types of enzyme-based biosensors. In this study,
      we have employed mesoporous silica SBA-15 to stably entrap horseradish peroxidase
      (HRP), and then deposited the loaded SBA-15 on the PANI modified platinum
      electrode to construct a GA/SBA-15(HRP)/PANI/Pt biosensor. The mesoporous
      structures and morphologies of SBA-15 with or without HRP were characterized.
      Enzymatic protein assays were employed to evaluate HRP immobilization efficiency.
      Our results demonstrated that the constructed biosensor displayed a fine linear
      correlation between cathodic response and H(2)O(2) concentration in the range of
      0.02 to 18.5 mM, with enhanced sensitivity. In particular, the current approach
      provided the PANI modified biosensor with improved stability for multiple
      measurements.

PMID- 22408547
TI  - A High Resolution Color Image Restoration Algorithm for Thin TOMBO Imaging
      Systems.
AB  - In this paper, we present a blind image restoration algorithm to reconstruct a
      high resolution (HR) color image from multiple, low resolution (LR), degraded and
      noisy images captured by thin (< 1mm) TOMBO imaging systems. The proposed
      algorithm is an extension of our grayscale algorithm reported in [1] to the case
      of color images. In this color extension, each Point Spread Function (PSF) of
      each captured image is assumed to be different from one color component to
      another and from one imaging unit to the other. For the task of image
      restoration, we use all spectral information in each captured image to restore
      each output pixel in the reconstructed HR image, i.e., we use the most efficient
      global category of point operations. First, the composite RGB color components of
      each captured image are extracted. A blind estimation technique is then applied
      to estimate the spectra of each color component and its associated blurring PSF.
      The estimation process is formed in a way that minimizes significantly the
      interchannel cross-correlations and additive noise. The estimated PSFs together
      with advanced interpolation techniques are then combined to compensate for blur
      and reconstruct a HR color image of the original scene. Finally, a histogram
      normalization process adjusts the balance between image color components,
      brightness and contrast. Simulated and experimental results reveal that the
      proposed algorithm is capable of restoring HR color images from degraded, LR and
      noisy observations even at low Signal-to-Noise Energy ratios (SNERs). The
      proposed algorithm uses FFT and only two fundamental image restoration
      constraints, making it suitable for silicon integration with the TOMBO imager.

PMID- 22408548
TI  - Advances in Hydrogen, Carbon Dioxide, and Hydrocarbon Gas Sensor Technology Using
      GaN and ZnO-Based Devices.
AB  - In this paper, we review our recent results in developing gas sensors for
      hydrogen using various device structures, including ZnO nanowires and GaN High
      Electron Mobility Transistors (HEMTs). ZnO nanowires are particularly interesting
      because they have a large surface area to volume ratio, which will improve
      sensitivity, and because they operate at low current levels, will have low power
      requirements in a sensor module. GaN-based devices offer the advantage of the
      HEMT structure, high temperature operation, and simple integration with existing
      fabrication technology and sensing systems. Improvements in sensitivity,
      recoverability, and reliability are presented. Also reported are demonstrations
      of detection of other gases, including CO(2) and C(2)H(4) using functionalized
      GaN HEMTs. This is critical for the development of lab-on-a-chip type systems and
      can provide a significant advance towards a market-ready sensor application.

PMID- 22408549
TI  - High resolution remote sensing of densely urbanised regions: a case study of Hong
      Kong.
AB  - Data on the urban environment such as climate or air quality is usually collected
      at a few point monitoring stations distributed over a city. However, the synoptic
      viewpoint of satellites where a whole city is visible on a single image permits
      the collection of spatially comprehensive data at city-wide scale. In spite of
      rapid developments in remote sensing systems, deficiencies in image resolution
      and algorithm development still exist for applications such as air quality
      monitoring and urban heat island analysis. This paper describes state-of-the-art
      techniques for enhancing and maximising the spatial detail available from
      satellite images, and demonstrates their applications to the densely urbanised
      environment of Hong Kong. An Emissivity Modulation technique for spatial
      enhancement of thermal satellite images permits modelling of urban microclimate
      in combination with other urban structural parameters at local scale. For air
      quality monitoring, a Minimum Reflectance Technique (MRT) has been developed for
      MODIS 500 m images. The techniques described can promote the routine utilization
      of remotely sensed images for environmental monitoring in cities of the 21(st)
      century.

PMID- 22408550
TI  - Secure cluster head sensor elections using signal strength estimation and ordered
      transmissions.
AB  - In clustered sensor networks, electing CHs (Cluster Heads) in a secure manner is
      very important because they collect data from sensors and send the aggregated
      data to the sink. If a compromised node is elected as a CH, it can illegally
      acquire data from all the members and even send forged data to the sink.
      Nevertheless, most of the existing CH election schemes have not treated the
      problem of the secure CH election. Recently, random value based protocols have
      been proposed to resolve the secure CH election problem. However, these schemes
      cannot prevent an attacker from suppressing its contribution for the change of CH
      election result and from selectively forwarding its contribution for the
      disagreement of CH election result. In this paper, we propose a modified random
      value scheme to prevent these disturbances. Our scheme dynamically adjusts the
      forwarding order of contributions and discards a received contribution when its
      signal strength is lower than the specified level to prevent these malicious
      actions. The simulation results have shown that our scheme effectively prevents
      attackers from changing and splitting an agreement of CH election result. Also,
      they have shown that our scheme is relatively energy-efficient than other
      schemes.

PMID- 22408551
TI  - A review of wireless sensor technologies and applications in agriculture and food
      industry: state of the art and current trends.
AB  - The aim of the present paper is to review the technical and scientific state of
      the art of wireless sensor technologies and standards for wireless communications
      in the Agri-Food sector. These technologies are very promising in several fields
      such as environmental monitoring, precision agriculture, cold chain control or
      traceability. The paper focuses on WSN (Wireless Sensor Networks) and RFID (Radio
      Frequency Identification), presenting the different systems available, recent
      developments and examples of applications, including ZigBee based WSN and
      passive, semi-passive and active RFID. Future trends of wireless communications
      in agriculture and food industry are also discussed.

PMID- 22408552
TI  - Optical slot-waveguide based biochemical sensors.
AB  - Slot-waveguides allow light to be guided and strongly confined inside a nanometer
      scale region of low refractive index. Thus stronger light-analyte interaction can
      be obtained as compared to that achievable by a conventional waveguide, in which
      the propagating beam is confined to the high-refractive-index core of the
      waveguide. In addition, slot-waveguides can be fabricated by employing CMOS
      compatible materials and technology, enabling miniaturization, integration with
      electronic, photonic and fluidic components in a chip, and mass production. These
      advantages have made the use of slot-waveguides for highly sensitive biochemical
      optical integrated sensors an emerging field. In this paper, recent achievements
      in slot-waveguide based biochemical sensing will be reviewed. These include slot
      waveguide ring resonator based refractometric label-free biosensors, label-based
      optical sensing, and nano-opto-mechanical sensors.

PMID- 22408553
TI  - Optimization-based channel constrained data aggregation routing algorithms in
      multi-radio wireless sensor networks.
AB  - In wireless sensor networks, data aggregation routing could reduce the number of
      data transmissions so as to achieve energy efficient transmission. However, data
      aggregation introduces data retransmission that is caused by co-channel
      interference from neighboring sensor nodes. This kind of co-channel interference
      could result in extra energy consumption and significant latency from
      retransmission. This will jeopardize the benefits of data aggregation. One
      possible solution to circumvent data retransmission caused by co-channel
      interference is to assign different channels to every sensor node that is within
      each other's interference range on the data aggregation tree. By associating each
      radio with a different channel, a sensor node could receive data from all the
      children nodes on the data aggregation tree simultaneously. This could reduce the
      latency from the data source nodes back to the sink so as to meet the user's
      delay QoS. Since the number of radios on each sensor node and the number of non
      overlapping channels are all limited resources in wireless sensor networks, a
      challenging question here is to minimize the total transmission cost under
      limited number of non-overlapping channels in multi-radio wireless sensor
      networks. This channel constrained data aggregation routing problem in multi
      radio wireless sensor networks is an NP-hard problem. I first model this problem
      as a mixed integer and linear programming problem where the objective is to
      minimize the total transmission subject to the data aggregation routing, channel
      and radio resources constraints. The solution approach is based on the Lagrangean
      relaxation technique to relax some constraints into the objective function and
      then to derive a set of independent subproblems. By optimally solving these
      subproblems, it can not only calculate the lower bound of the original primal
      problem but also provide useful information to get the primal feasible solutions.
      By incorporating these Lagrangean multipliers as the link arc weight, the
      optimization-based heuristics are proposed to get energy-efficient data
      aggregation tree with better resource (channel and radio) utilization. From the
      computational experiments, the proposed optimization-based approach is superior
      to existing heuristics under all tested cases.

PMID- 22408554
TI  - Effect of cadmium chloride on metallothionein levels in carp.
AB  - Due to anthropogenic activities, heavy metals still represent a threat for
      various trophic levels. If aquatic animals are exposed to heavy metals, we can
      obviously observe considerable toxicity. It is well known that organisms treated
      with heavy metals synthesize low molecular mass compounds rich in cysteine. In
      this work the effects of cadmium chloride (2.5, 5, 7.5, 10 and 12.5 mg/L) on
      common carp (Cyprinus carpio) was investigated. We determined cadmium content in
      tissue of muscle, liver and kidney by atomic absorption spectrometry with
      electrothermal atomization and content of metallothionein (MT) in the same
      tissues by the Brdicka reaction. Electrochemical methods can be considered as
      suitable and sensitive tools for MT determination in carp tissues. Results of our
      study showed a gradually enhancing of cadmium content in muscle with time and
      dose of cadmium chloride in water. MT levels in liver reached both high levels
      (above 130 ng/g) in fish exposed to 2.5, 5 and 7.5 mg/L and low level (to 50
      ng/g) in fish exposed to 10 and 12.5 mg/L of cadmium chloride. This finding
      confirms that the synthesis of metallothioneins and binding capacity of these
      proteins is restricted.

PMID- 22408556
TI  - Medium Access Control for Opportunistic Concurrent Transmissions under Shadowing
      Channels.
AB  - We study the problem of how to alleviate the exposed terminal effect in multi-hop
      wireless networks in the presence of log-normal shadowing channels. Assuming node
      location information, we propose an extension of the IEEE 802.11 MAC protocol
      that sched-ules concurrent transmissions in the presence of log-normal shadowing,
      thus mitigating the exposed terminal problem and improving network throughput and
      delay performance. We observe considerable improvements in throughput and delay
      achieved over the IEEE 802.11 MAC under various network topologies and channel
      conditions in ns-2 simulations, which justify the importance of considering
      channel randomness in MAC protocol design for multi-hop wireless networks.

PMID- 22408555
TI  - Microfluidic systems for pathogen sensing: a review.
AB  - Rapid pathogen sensing remains a pressing issue today since conventional
      identification methodsare tedious, cost intensive and time consuming, typically
      requiring from 48 to 72 h. In turn, chip based technologies, such as microarrays
      and microfluidic biochips, offer real alternatives capable of filling this
      technological gap. In particular microfluidic biochips make the development of
      fast, sensitive and portable diagnostic tools possible, thus promising rapid and
      accurate detection of a variety of pathogens. This paper will provide a broad
      overview of the novel achievements in the field of pathogen sensing by focusing
      on methods and devices that compliment microfluidics.

PMID- 22408557
TI  - On the relevance of using open wireless sensor networks in environment
      monitoring.
AB  - This paper revisits the problem of the readiness for field deployments of
      wireless sensor networks by assessing the relevance of using Open Hardware and
      Software motes for environment monitoring. We propose a new prototype wireless
      sensor network that fine-tunes SquidBee motes to improve the life-time and
      sensing performance of an environment monitoring system that measures
      temperature, humidity and luminosity. Building upon two outdoor sensing
      scenarios, we evaluate the performance of the newly proposed energy-aware
      prototype solution in terms of link quality when expressed by the Received Signal
      Strength, Packet Loss and the battery lifetime. The experimental results reveal
      the relevance of using the Open Hardware and Software motes when setting up
      outdoor wireless sensor networks.

PMID- 22408558
TI  - Applications of remote sensing to alien invasive plant studies.
AB  - Biological invasions can affect ecosystems across a wide spectrum of bioclimatic
      conditions. Therefore, it is often important to systematically monitor the spread
      of species over a broad region. Remote sensing has been an important tool for
      large-scale ecological studies in the past three decades, but it was not commonly
      used to study alien invasive plants until the mid 1990s. We synthesize previous
      research efforts on remote sensing of invasive plants from spatial, temporal and
      spectral perspectives. We also highlight a recently developed state-of-the-art
      image fusion technique that integrates passive and active energies concurrently
      collected by an imaging spectrometer and a scanning-waveform light detection and
      ranging (LiDAR) system, respectively. This approach provides a means to detect
      the structure and functional properties of invasive plants of different canopy
      levels. Finally, we summarize regional studies of biological invasions using
      remote sensing, discuss the limitations of remote sensing approaches, and
      highlight current research needs and future directions.

PMID- 22408559
TI  - A Novel Label-Free Optical Biosensor Using Synthetic Oligonucleotides from E.
      coli O157:H7: Elementary Sensitivity Tests.
AB  - SiO(2)-TiO(2) thin films for use as fiber optic guiding layers of optical DNA
      biosensors were fabricated by the sol-gel dip coating technique. The chemical
      structure and the surface morphology of the films were characterized before
      immobilization. Single probe DNA strands were immobilized on the surface and the
      porosity of the films before the hybridization process was measured. Refractive
      index values of the films were measured using a Metricon 2010 prism coupler. On
      the surface of each film, 12 different spots were taken for measurement and
      calculation of the mean refractive index values with their standard deviations.
      The increased refractive index values after the immobilization of single DNA
      strands indicated that immobilization was successfully achieved. A further
      refractive index increase after the hybridization with target single DNA strands
      showed the possibility of detection of the E. coli O157:H7 EDL933 species using
      strands of 20-mers (5'-TAATATCGGTTGCGGAGGTG -3') sequence.

PMID- 22408560
TI  - Distributed joint source-channel coding in wireless sensor networks.
AB  - Considering the fact that sensors are energy-limited and the wireless channel
      conditions in wireless sensor networks, there is an urgent need for a low
      complexity coding method with high compression ratio and noise-resisted features.
      This paper reviews the progress made in distributed joint source-channel coding
      which can address this issue. The main existing deployments, from the theory to
      practice, of distributed joint source-channel coding over the independent
      channels, the multiple access channels and the broadcast channels are introduced,
      respectively. To this end, we also present a practical scheme for compressing
      multiple correlated sources over the independent channels. The simulation results
      demonstrate the desired efficiency.

PMID- 22408561
TI  - CoCMA: Energy-Efficient Coverage Control in Cluster-Based Wireless Sensor
      Networks Using a Memetic Algorithm.
AB  - Deployment of wireless sensor networks (WSNs) has drawn much attention in recent
      years. Given the limited energy for sensor nodes, it is critical to implement
      WSNs with energy efficiency designs. Sensing coverage in networks, on the other
      hand, may degrade gradually over time after WSNs are activated. For mission
      critical applications, therefore, energy-efficient coverage control should be
      taken into consideration to support the quality of service (QoS) of WSNs.
      Usually, coverage-controlling strategies present some challenging problems: (1)
      resolving the conflicts while determining which nodes should be turned off to
      conserve energy; (2) designing an optimal wake-up scheme that avoids awakening
      more nodes than necessary. In this paper, we implement an energy-efficient
      coverage control in cluster-based WSNs using a Memetic Algorithm (MA)-based
      approach, entitled CoCMA, to resolve the challenging problems. The CoCMA contains
      two optimization strategies: a MA-based schedule for sensor nodes and a wake-up
      scheme, which are responsible to prolong the network lifetime while maintaining
      coverage preservation. The MA-based schedule is applied to a given WSN to avoid
      unnecessary energy consumption caused by the redundant nodes. During the network
      operation, the wake-up scheme awakens sleeping sensor nodes to recover coverage
      hole caused by dead nodes. The performance evaluation of the proposed CoCMA was
      conducted on a cluster-based WSN (CWSN) under either a random or a uniform
      deployment of sensor nodes. Simulation results show that the performance yielded
      by the combination of MA and wake-up scheme is better than that in some existing
      approaches. Furthermore, CoCMA is able to activate fewer sensor nodes to monitor
      the required sensing area.

PMID- 22408562
TI  - Improving temporal coverage of an energy-efficient data extraction algorithm for
      environmental monitoring using wireless sensor networks.
AB  - Collecting raw data from a wireless sensor network for environmental monitoring
      applications can be a difficult task due to the high energy consumption involved.
      This is especially difficult when the application requires specialized sensors
      that have very high energy consumption, e.g. hydrological sensors for monitoring
      marine environments. This paper introduces a technique for reducing energy
      consumption by minimizing sensor sampling operations. In addition, we illustrate
      how a randomized algorithm can be used to improve temporal coverage such that the
      time between the occurrence of an event and its detection can be minimized. We
      evaluate our approach using real data collected from a sensor network deployment
      on the Great Barrier Reef.

PMID- 22408563
TI  - Metal Oxides and Ion-Exchanging Surfaces as pH Sensors in Liquids: State-of-the
      Art and Outlook.
AB  - Novel applications of online pH determinations at temperatures from -35  degrees
      C to 130  degrees C in technical and biological media, which are all but ideal
      aqueous solutions, require new approaches to pH monitoring. The glass electrode,
      introduced nearly hundred years ago, and chemical sensors based on field effect
      transistors (ISFET) show specific drawbacks with respect to handling and long
      time stability. Proton sensitive metal oxides seem to be a promising and
      alternative to the state-of-the-art measuring methods, and might overcome some
      problems of classical hydrogen electrodes and reference electrodes.

PMID- 22408564
TI  - Design of a smart ultrasonic transducer for interconnecting machine applications.
AB  - A high-frequency ultrasonic transducer for copper or gold wire bonding has been
      designed, analyzed, prototyped and tested. Modeling techniques were used in the
      design phase and a practical design procedure was established and used. The
      transducer was decomposed into its elementary components. For each component, an
      initial design was obtained with simulations using a finite elements model (FEM).
      Simulated ultrasonic modules were built and characterized experimentally through
      the Laser Doppler Vibrometer (LDV) and electrical resonance spectra. Compared
      with experimental data, the FEM could be iteratively adjusted and updated. Having
      achieved a remarkably highly-predictive FEM of the whole transducer, the design
      parameters could be tuned for the desired applications, then the transducer is
      fixed on the wire bonder with a complete holder clamping was calculated by the
      FEM. The approach to mount ultrasonic transducers on wire bonding machines also
      is of major importance for wire bonding in modern electronic packaging. The
      presented method can lead to obtaining a nearly complete decoupling clamper
      design of the transducer to the wire bonder.

PMID- 22408565
TI  - Study of Alternative GPS Network Meteorological Sensors in Taiwan: Case Studies
      of the Plum Rains and Typhoon Sinlaku.
AB  - Plum rains and typhoons are important weather systems in the Taiwan region. They
      can cause huge economic losses, but they are also considered as important water
      resources as they strike Taiwan annually and fill the reservoirs around the
      island. There are many meteorological sensors available for investigating the
      characteristics of weather and climate systems. Recently, the use of GPS as an
      alternative meteorological sensor has become popular due to the catastrophic
      impact of global climate change. GPS provides meteorological parameters mainly
      from the atmosphere. Precise Point Positioning (PPP) is a proven algorithm that
      has attracted attention in GPS related studies. This study uses GPS measurements
      collected at more than fifty reference stations of the e-GPS network in Taiwan.
      The first data set was collected from June 1st 2008 to June 7th 2008, which
      corresponds to the middle of the plum rain season in Taiwan. The second data set
      was collected from September 11th to September 17th 2008 during the landfall of
      typhoon Sinlaku. The data processing strategy is to process the measurements
      collected at the reference stations of the e-GPS network using the PPP technique
      to estimate the zenith tropospheric delay (ZTD) values of the sites; thus, the
      correlations between the ZTD values and the variation of rainfall during the plum
      rains and typhoon are analyzed. In addition, several characteristics of the
      meteorological events are identified using spatial and temporal analyses of the
      ZTD values estimated with the GPS network PPP technique.

PMID- 22408566
TI  - A Hop-Count Analysis Scheme for Avoiding Wormhole Attacks in MANET.
AB  - MANET, due to the nature of wireless transmission, has more security issues
      compared to wired environments. A specific type of attack, the Wormhole attack
      does not require exploiting any nodes in the network and can interfere with the
      route establishment process. Instead of detecting wormholes from the role of
      administrators as in previous methods, we implement a new protocol, MHA, using a
      hop-count analysis from the viewpoint of users without any special environment
      assumptions. We also discuss previous works which require the role of
      administrator and their reliance on impractical assumptions, thus showing the
      advantages of MHA.

PMID- 22408567
TI  - Cancer and radiation therapy: current advances and future directions.
AB  - In recent years remarkable progress has been made towards the understanding of
      proposed hallmarks of cancer development and treatment. However with its
      increasing incidence, the clinical management of cancer continues to be a
      challenge for the 21st century. Treatment modalities comprise of radiation
      therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Radiation
      therapy remains an important component of cancer treatment with approximately 50%
      of all cancer patients receiving radiation therapy during their course of
      illness; it contributes towards 40% of curative treatment for cancer. The main
      goal of radiation therapy is to deprive cancer cells of their multiplication
      (cell division) potential. Celebrating a century of advances since Marie Curie
      won her second Nobel Prize for her research into radium, 2011 has been designated
      the Year of Radiation therapy in the UK. Over the last 100 years, ongoing
      advances in the techniques of radiation treatment and progress made in
      understanding the biology of cancer cell responses to radiation will endeavor to
      increase the survival and reduce treatment side effects for cancer patients. In
      this review, principles, application and advances in radiation therapy with their
      biological end points are discussed.

PMID- 22408568
TI  - Isolated biliary cryptococcosis manifesting as obstructive jaundice in an
      immunocompetent adult.
AB  - Cryptococcosis is a symptomatic fungal infection caused by Cryptococcus, which
      frequently occurs in patients who are immunologically compromised or chronically
      ill. Localized involvement of the hepatobiliary system in an immunocompetent
      adult is extremely rare. We report a unique case of isolated biliary
      cryptococcosis manifesting as obstructive jaundice and mimicking hilar
      cholangiocarcinoma in an immunocompetent woman. By integrating surgical and
      antifungal drug therapy, the disease was effectively controlled. Despite an
      increasing incidence of biliary malignancies, hepatobiliary surgeons and
      gastroenterologists must maintain a high index of suspicion for other rare
      possibilities of non-specific biliary inflammation.

PMID- 22408569
TI  - Congenital bronchial atresia: diagnosis and treatment.
AB  - This study aimed to retrospectively summarize the clinical signs, diagnosis, and
      treatment of congenital bronchial atresia (CBA) in 12 patients. Chest radiographs
      and computed tomographic (CT) images of 12 patients with CBA treated in the
      Chinese People's Liberation Army General Hospital were reviewed. Analysis of
      chest radiographs revealed ten patients had hilar mass-like shadows and two had
      pneumonia-like shadows; most patients (n = 8) showed hyperlucency of the
      peripheral lung fields. CT revealed a mucocele in all the patients (n = 12); the
      mucoceles were round in four patients and club-like in eight. In 80% of the cases
      (n = 10), associated anomalies, including occlusions of the bronchus central to
      the mucocele, emphysematous changes of the peripheral lung fields, bronchogenic
      cyst, and anomalous branching of the bronchial tree and vascular structure were
      observed. CBA was detected in the right lobe in eight patients and the left lobe
      in the remaining four. No surgical intervention was performed in 5 CBA patients
      and the remaining 7 patients underwent surgery, including lobectomy in 5 patients
      and local resection in 2 patients. Among these 7 patients, 3 had a preoperative
      diagnosis of malignant disease, and the remaining 4 had severe clinical symptoms
      that could not be effectively treated by medicines. All patients were followed
      up, and none experienced obvious discomfort. CBA is a relatively rare and benign
      malformation disease. Chest CT is the procedure of choice for diagnosis. The
      presence of a bronchocele and surrounding emphysematous changes are typical
      radiologic findings in CBA. Surgery should be reserved only for patients with
      serious complications secondary to the atretic bronchus.

PMID- 22408570
TI  - Strangulated intestinal obstruction secondary to a typical obturator hernia: a
      case report with literature review.
AB  - Obturator hernia is a rare pelvic hernia with incidence of 1%. It's a significant
      cause of intestinal obstruction in emaciated elderly women. Delayed diagnosis and
      surgical intervention contributed to its relatively high morbidity and mortality.
      We present a typical case of obturator hernia with positive Howship-Romberg sign
      and Hannington-Kiff sign. The diagnosis was confirmed by spiral CT
      preoperatively. During the emergency laparotomy, the incarcerated intestine was
      reduced and removed. Obturator foramen was repaired by simple suture. The patient
      recovered uneventfully and no recurrence occurred during the follow-up. The
      obturator hernia should be included in the differential diagnosis if clinically
      suspected. Early diagnosis and prompt surgical treatment are essential to reduce
      the morbidity and mortality associated with obturator hernia.

PMID- 22408571
TI  - Effects of STAT3 gene silencing and rapamycin on apoptosis in hepatocarcinoma
      cells.
AB  - The PI3K/Akt/mTOR and JAK/STAT3 signaling pathways are important for regulating
      apoptosis, and are frequently activated in cancers. In this study, we targeted
      STAT3 and mTOR in human hepatocellular carcinoma Bel-7402 cells and examined the
      subsequent alterations in cellular apoptosis. The expression of STAT3 was
      silenced with small interfering RNA (siRNA)-expressing plasmid. The activity of
      mTOR was inhibited using rapamycin. Following treatment, Annexin V/propidium
      iodide staining followed by flow cytometry and Hoechst33258 immunofluorescence
      staining was used to examine cellular apoptosis. JC-1 staining was used to
      monitor depolarization of mitochondrial membrane (DeltaPsim). Furthermore, the
      expression of activated caspase 3 protein was analyzed by Western blotting.
      Compared to non-treated or control siRNA-transfected cells, significantly higher
      levels of apoptosis were detected in siSTAT3-transfected or rapamycin-treated
      cells (P < 0.05), which was further enhanced in cells targeted for both molecules
      (P < 0.05). The pro-apoptotic effects were accompanied with concomitant
      depolarization of mitochondrial membrane and up-regulation of activated caspase
      3. Combined treatments using rapamycin and STAT3 gene silencing significantly
      increases apoptosis in Bel-7402 cells, displaying more dramatic effect than any
      single treatment. This study provides evidence for targeting multiple molecules
      in cancer therapy.

PMID- 22408572
TI  - Hem-o-lok clip found in common bile duct after laparoscopic cholecystectomy and
      common bile duct exploration: a clinical analysis of 8 cases.
AB  - Currently laparoscopic cholecystectomy (LC) and common bile duct exploration
      (LCBDE) has become the standard surgical procedure for cholecystolithiasis and
      choledocholithiasis. During the operation cystic duct and vessels are usually
      controlled by Hem-o-lok clips. However, recently we found clips dropping into CBD
      in 8 patients during fiberoptic choledochoscope 2-3 months after operation.
      Therefore, there is risk that clip can migrate during postoperative period, which
      probably lead to hemorrhage and bile leakage after LC if this occurs within
      postoperative few days, or even cause recurrent stone in CBD. So, using of Hem-o
      lok clips may be not a safe method to control vessels and cystic duct during LC.
      To our knowledge, this condition has not previously been reported. In our view,
      other more effective and safe method ligating cystic duct and gallbladder
      vessels, such as effective and convenient thread knotting method, should be
      investigated.

PMID- 22408573
TI  - Relations of Early Goal Blockage Response and Gender to Subsequent Tantrum
      Behavior.
AB  - Infants and their mothers participated in a longitudinal study of the sequelae of
      infant goal blockage responses. Four-month-old infants participated in a standard
      contingency learning/goal blockage procedure during which anger and sad facial
      expressions to the blockage were coded. When infants were 12- and 20- months-old,
      mothers completed a questionnaire about their children's tantrums. Tantrum scores
      increased with age and boys tended to show more tantrum behavior than girls.
      Anger expressed to goal blockage at 4 months was unrelated to tantrum behavior.
      There was a gender by sad expression interaction. Girls who expressed sadness in
      response to the goal blockage had lower total tantrum scores than boys; otherwise
      there was no difference. These results suggest that tantrums of infants who
      display sad, not anger expression, in response to goal blockage, are
      differentially influenced by children's gender.

PMID- 22408574
TI  - A reappraisal of Microthyriaceae.
AB  - The family Microthyriaceae sensuLumbsch and Huhndorf 2010 is a poorly known but
      interesting family comprising 50 genera consisting of foliar epiphytes or
      saprobes on dead leaves and stems. We re-visited the family based on examinations
      of generic types where possible. Members are distributed in Aulographaceae,
      Asterinaceae, Microthyriaceae, Micropeltidaceae and Palmulariaceae and notes are
      provided on each of these families. Nine genera are transferred from
      Microthyriaceae to Asterinaceae, and two to Aulographaceae based on the splitting
      or dissolving nature of the thyriothecia to release ascospores. New sequence data
      for a number of species and genera are provided. Microthyriaceous members growing
      on other fungi and lichens differ from Microthyriaceae sensu stricto and the
      family Trichothyriaceae is reinstated to accommodate these taxa. Other genera of
      Microthyriaceae belong in Rhytismataceae, Stictidaceae, Venturiales incertae
      cedis, Dothideomyetes genera incertae cedis, Hypocreales incertae cedis and
      Ascomycota genera incertae cedis. The family Microthyriaceae is reduced to seven
      genera characterised by superficial, flattened thyriothecia, with the cells of
      the upper wall radiating in parallel arrangement from the distinct central
      ostiolar opening, while the lower peridium is generally poorly developed.
      Sequence data is provided for five species with thyriothecia and Paramicrothyrium
      and Neomicrothyrium are described as new genera and Micropeltis zingiberacicola
      is introduced as a new species. Our phylogenetic analysis underscores the high
      genetic diversity for thyriotheciate species and there is no clear clade that can
      be well defined as Microthyriales. Nuclear ribosomal data support multiple
      polyphyletic lineages within Microthyriaceae and Micropeltidaceae. Some
      unexpected DNA based phylogenetic relationships such as those between Muyocopron
      and Saccardoella will require corroboration with more complete taxon sampling as
      well as additional non ribosomal markers. There are few differences between
      Aulographaceae, Asterinaceae and Palmulariaceae and these families may need
      synonymising.

PMID- 22408575
TI  - Frequency distribution signatures and classification of within-object pixels.
AB  - The premise of geographic object-based image analysis (GEOBIA) is that image
      objects are composed of aggregates of pixels that correspond to earth surface
      features of interest. Most commonly, image-derived objects (segments) or objects
      associated with predefined land units (e.g., agricultural fields) are classified
      using parametric statistical characteristics (e.g., mean and standard deviation)
      of the within-object pixels. The objective of this exploratory study was to
      examine the between- and within-class variability of frequency distributions of
      multispectral pixel values, and to evaluate a quantitative measure and
      classification rule that exploits the full pixel frequency distribution of within
      object pixels (i.e., histogram signatures) compared to simple parametric
      statistical characteristics. High spatial resolution Quickbird satellite
      multispectral data of Accra, Ghana were evaluated in the context of mapping land
      cover and land use and socioeconomic status. Results show that image objects
      associated with land cover and land use types can have characteristic, non-normal
      frequency distributions (histograms). Signatures of most image objects tended to
      match closely the training signature of a single class or sub-class. Curve
      matching approaches to classifying multi-pixel frequency distributions were found
      to be slightly more effective than standard statistical classifiers based on a
      nearest neighbor classifier.

PMID- 22408576
TI  - Where to Publish and Find Ontologies? A Survey of Ontology Libraries.
AB  - One of the key promises of the Semantic Web is its potential to enable and
      facilitate data interoperability. The ability of data providers and application
      developers to share and reuse ontologies is a critical component of this data
      interoperability: if different applications and data sources use the same set of
      well defined terms for describing their domain and data, it will be much easier
      for them to "talk" to one another. Ontology libraries are the systems that
      collect ontologies from different sources and facilitate the tasks of finding,
      exploring, and using these ontologies. Thus ontology libraries can serve as a
      link in enabling diverse users and applications to discover, evaluate, use, and
      publish ontologies. In this paper, we provide a survey of the growing-and
      surprisingly diverse-landscape of ontology libraries. We highlight how the
      varying scope and intended use of the libraries a ects their features, content,
      and potential exploitation in applications. From reviewing eleven ontology
      libraries, we identify a core set of questions that ontology practitioners and
      users should consider in choosing an ontology library for finding ontologies or
      publishing their own. We also discuss the research challenges that emerge from
      this survey, for the developers of ontology libraries to address.

PMID- 22408577
TI  - Efficacy of polyethylene glycol adhesion barrier after gynecological laparoscopic
      surgery: Results of a randomized controlled pilot study.
AB  - Postoperative adhesions are the most frequent complication of peritoneal surgery,
      causing small bowel obstruction, female infertility and chronic pain. This pilot
      study assessed the efficacy of a sprayable polyethylene glycol (PEG) barrier in
      the prevention of de novo adhesions. 16 patients undergoing laparoscopic
      gynecological surgery were randomly assigned by shuffled sealed envelopes to
      receive either the adhesion barrier or no adhesion prevention. Incidence and
      severity of adhesions were scored at eight sites in the pelvis and reassessed by
      second look laparoscopy. Adhesion prevention was considered successful if no de
      novo adhesion were found at second look laparoscopy. One patient was excluded
      before randomization. Nine patients were randomized to treatment and six patients
      to control group. De novo adhesions were found in 0/9 patients who received the
      PEG barrier compared to 4/6 without adhesion prevention (0% vs. 67%, P = 0.01).
      Reduction in adhesion score was significantly greater in patients receiving PEG
      barrier (-2.6 vs. -0.06, P = 0.03). Meta-analysis of three randomized trials
      demonstrated that PEG barrier reduces the incidence of adhesions (odds ratio [OR]
      = 0.27; 95% CI 0.11-0.67). From this study, PEG barrier seems effective in
      reducing postoperative formation of de novo adhesions.

PMID- 22408578
TI  - Increasing experience in laparoscopic staging of early ovarian cancer.
AB  - We assessed the effect of increasing experience of a single surgeon (learning
      curve) in the laparoscopic staging procedure for women with early ovarian cancer
      and compared the results with the literature. We retrospectively analysed a total
      of 25 women with apparent early-stage ovarian cancer who underwent a laparoscopic
      staging procedure by the same surgeon. Three time periods, based on date of
      surgery, were compared with respect to operating time, amount of lymph nodes
      harvested and surgical outcome. There was no significant difference in operation
      time, estimated blood loss and hospital stay between the three periods. There
      was, however, a significant increase in the median number of pelvic and para
      aortal lymph nodes harvested (group1 = 6.5, group 2 = 8.0 and group 3 = 21.0; P <
      0.005). For the total period, median operation time was 235 min and median
      estimated blood loss was 100 ml. The median length of hospital stay was 4.0 days.
      Two intraoperative and two postoperative complications occurred. The upstaging
      rate was 32%. The mean interval between initial surgery and laparoscopic staging
      was 51.2 days. Mean duration of follow-up was 43 months, range (1-116 months).
      Five (20%) patients had recurrences, and two (8%) patients died of the disease.
      In conclusion, there is a significant learning curve for the laparoscopic full
      staging procedure in ovarian cancer. In our study this is mainly reflected in the
      amount of lymph nodes harvested and not in the total operating time.

PMID- 22408579
TI  - C-Galactosylceramide: Synthesis and Immunology.
AB  - A synthetic C-glycoside, alpha-C-galactosylceramide, is an active immunostimulant
      in mice. It displays better activity than alpha-O-galactosylceramide in several
      disease models. Syntheses of several alpha-C-galactosylceramides are described.
      Experiments that probe its immunostimulant activity are outlined. Possible
      explanations for its superior activity are discussed.

PMID- 22408580
TI  - The costs of climate change: a study of cholera in Tanzania.
AB  - Increased temperatures and changes in rainfall patterns as a result of climate
      change are widely recognized to entail potentially serious consequences for human
      health, including an increased risk of diarrheal diseases. This study integrates
      historical data on temperature and rainfall with the burden of disease from
      cholera in Tanzania and uses socioeconomic data to control for the impacts of
      general development on the risk of cholera. The results show a significant
      relationship between temperature and the incidence of cholera. For a 1 degree
      Celsius temperature increase the initial relative risk of cholera increases by 15
      to 29 percent. Based on the modeling results, we project the number and costs of
      additional cases of cholera that can be attributed to climate change by 2030 in
      Tanzania for a 1 and 2 degree increase in temperatures, respectively. The total
      costs of cholera attributable to climate change are shown to be in the range of
      0.32 to 1.4 percent of GDP in Tanzania 2030. The results provide useful insights
      into national-level estimates of the implications of climate change on the health
      sector and offer information which can feed into both national and international
      debates on financing and planning adaptation.

PMID- 22408581
TI  - High calorie, low nutrient food/beverage intake and video gaming in children as
      potential signals for addictive behavior.
AB  - Little is known about the co-occurrence of health risk behaviors in childhood
      that may signal later addictive behavior. Using a survey, this study evaluated
      high calorie, low nutrient HCLN intake and video gaming behaviors in 964 fourth
      grade children over 18 months, with stress, sensation-seeking, inhibitory
      control, grades, perceived safety of environment, and demographic variables as
      predictors. SEM and growth curve analyses supported a co-occurrence model with
      some support for addiction specificity. Male gender, free/reduced lunch, low
      perceived safety and low inhibitory control independently predicted both gaming
      and HCLN intake. Ethnicity and low stress predicted HCLN. The findings raise
      questions about whether living in some impoverished neighborhoods may contribute
      to social isolation characterized by staying indoors, and HCLN intake and video
      gaming as compensatory behaviors. Future prevention programs could include skills
      training for inhibitory control, combined with changes in the built environment
      that increase safety, e.g., implementing Safe Routes to School Programs.

PMID- 22408583
TI  - Microbiological evaluation of water quality from urban watersheds for domestic
      water supply improvement.
AB  - Agricultural and urban runoffs may be major sources of pollution of water bodies
      and major sources of bacteria affecting the quality of drinking water. Of the
      different pathways by which bacterial pathogens can enter drinking water, this
      one has received little attention to date; that is, because soils are often
      considered to be near perfect filters for the transport of bacterial pathogens
      through the subsoil to groundwater. The goals of this study were to determine the
      distribution, diversity, and antimicrobial resistance of pathogenic Escherichia
      coli isolates from low flowing river water and sediment with inputs from
      different sources before water is discharged into ground water and to compare
      microbial contamination in water and sediment at different sampling sites. Water
      and sediment samples were collected from 19 locations throughout the watershed
      for the isolation of pathogenic E. coli. Heterotrophic plate counts and E. coli
      were also determined after running tertiary treated water through two tanks
      containing aquifer sand material. Presumptive pathogenic E. coli isolates were
      obtained and characterized for virulent factors and antimicrobial resistance.
      None of the isolates was confirmed as Shiga toxin E. coli (STEC), but as others,
      such as enterotoxigenic E. coli (ETEC). Pulsed field gel electrophoresis (PFGE)
      was used to show the diversity E. coli populations from different sources
      throughout the watershed. Seventy six percent of the isolates from urban sources
      exhibited resistance to more than one antimicrobial agent. A subsequent
      filtration experiment after water has gone through filtration tanks containing
      aquifer sand material showed that there was a 1 to 2 log reduction in E. coli in
      aquifer sand tank. Our data showed multiple strains of E. coli without virulence
      attributes, but with high distribution of resistant phenotypes. Therefore, the
      occurrence of E. coli with multiple resistances in the environment is a matter of
      great concern due to possible transfer of resistant genes from nonpathogenic to
      pathogenic strains that may result in increased duration and severity of
      morbidity.

PMID- 22408584
TI  - The antimicrobial properties of cedar leaf (Thuja plicata) oil; a safe and
      efficient decontamination agent for buildings.
AB  - Cedar leaf oil (CLO), derived from the Western red cedar, Thuja plicata, was
      evaluated as a safe and acceptable broad spectrum antimicrobial agent, with a
      view to its potential applications in buildings, including the alleviation of
      sick building syndrome. Various Gram-positive and Gram-negative human bacteria,
      and two fungal organisms, all known to be common environmental sources of
      potential infection, were selected and tested quantitatively, and all of them
      were found to be susceptible to CLO liquid and vapor. Bacterial spores and
      Aspergillus niger were sensitive, although less so than the vegetative bacteria.
      Similar tests with cultured human lung cells showed that continuous exposure to
      CLO vapor for at least 60 minutes was not toxic to the cells. Based on these
      results, CLO shows promise as a prospective safe, green, broad-spectrum anti
      microbial agent for decontamination of buildings.

PMID- 22408582
TI  - Generational association studies of dopaminergic genes in reward deficiency
      syndrome (RDS) subjects: selecting appropriate phenotypes for reward dependence
      behaviors.
AB  - Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an
      insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome
      (RDS). RDS results from a dysfunction in the "brain reward cascade," a complex
      interaction among neurotransmitters (primarily dopaminergic and opioidergic).
      Individuals with a family history of alcoholism or other addictions may be born
      with a deficiency in the ability to produce or use these neurotransmitters.
      Exposure to prolonged periods of stress and alcohol or other substances also can
      lead to a corruption of the brain reward cascade function. We evaluated the
      potential association of four variants of dopaminergic candidate genes in RDS
      (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine
      transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]). METHODOLOGY: We
      genotyped an experimental group of 55 subjects derived from up to five
      generations of two independent multiple-affected families compared to rigorously
      screened control subjects (e.g., N = 30 super controls for DRD2 gene
      polymorphisms). Data related to RDS behaviors were collected on these subjects
      plus 13 deceased family members. RESULTS: Among the genotyped family members, the
      DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more
      often found in the RDS families vs. controls. The TaqA1 allele occurred in 100%
      of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No
      significant differences were found between the experimental and control positive
      rates for the other variants. CONCLUSIONS: Although our sample size was limited,
      and linkage analysis is necessary, the results support the putative role of
      dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a
      nonspecific RDS phenotype and informs an understanding of how evaluating single
      subset behaviors of RDS may lead to spurious results. Utilization of a
      nonspecific "reward" phenotype may be a paradigm shift in future association and
      linkage studies involving dopaminergic polymorphisms and other neurotransmitter
      gene candidates.

PMID- 22408585
TI  - Extensive internet involvement--addiction or emerging lifestyle?
AB  - In the discussions for the future DSM-5, the Substance-Related Disorders Work
      Group has been addressing "addiction-like" behavioral disorders such as "Internet
      addiction" to possibly be considered as potential additions for the diagnostic
      system. Most research aiming to specify and define the concept of Internet
      addiction (or: Excessive/Compulsive/Problematic Internet Use--PIU), takes its
      point of departure in conventional terminology for addiction, based in
      established DSM indicators. Still, it is obvious that the divide between
      characteristics of addiction and dimensions of new lifestyles built on
      technological progress is problematic and far from unambiguous. Some of these
      research areas are developing from the neurobiological doctrine of addiction as
      not being tied to specific substances. The concept of "behavioral addictions",
      based on biological mechanisms such as the reward systems of the brain, has been
      launched. The problems connected to this development are in this study discussed
      and reflected with data from a Swedish survey on Internet use (n = 1,147). Most
      Swedes (85%) do use the Internet to some degree. The prevalence of excessive use
      parallels other similar countries. Respondents in our study spend (mean value)
      9.8 hours per week online at home, only 5 percent spend more than 30 hours per
      week. There are both positive and negative social effects at hand. Many
      respondents have more social contacts due to the use of Internet, but there is a
      decline in face-to-face contacts. About 40% of the respondents indicate some
      experience of at least one problem related to Internet use, but only 1.8% marked
      the presence of all problems addressed. Most significant predictors for problem
      indicators, except for age, relate to "time" and time consuming activities such
      as gaming, other activities online or computer skills.

PMID- 22408586
TI  - Assessment of indoor air pollution in homes with infants.
AB  - Infants spend most of their indoor time at home; however, residential air quality
      is poorly understood. We investigated the air quality of infants' homes in the
      New England area of the U.S. Participants (N = 53) were parents of infants (0-6
      months) who completed telephone surveys to identify potential pollutant sources
      in their residence. Carbon monoxide (CO), carbon dioxide (CO(2)), particulate
      matter with aerodynamic diameter <=0.5 um (PM(0.5)), and total volatile organic
      compounds (TVOCs) were measured in 10 homes over 4-7 days, and levels were
      compared with health-based guidelines. Pollutant levels varied substantially
      across homes and within homes with overall levels for some homes up to 20 times
      higher than for other homes. Average levels were 0.85 ppm, 663.2 ppm, 18.7
      ug/m(3), and 1626 ug/m(3) for CO, CO(2), PM(0.5), and TVOCs, respectively. CO(2),
      TVOCs, and PM(0.5) levels exceeded health-based indoor air quality guidelines.
      Survey results suggest that nursery renovations and related potential pollutant
      sources may be associated with differences in urbanicity, income, and presence of
      older children with respiratory ailments, which could potentially confound health
      studies. While there are no standards for indoor residential air quality, our
      findings suggest that additional research is needed to assess indoor pollution
      exposure for infants, which may be a vulnerable population.

PMID- 22408587
TI  - Mass casualties and health care following the release of toxic chemicals or
      radioactive material--contribution of modern biotechnology.
AB  - Catastrophic chemical or radiological events can cause thousands of casualties.
      Such disasters require triage procedures to identify the development of health
      consequences requiring medical intervention. Our objective is to analyze recent
      advancements in biotechnology for triage in mass emergency situations. In
      addition to identifying persons "at risk" of developing health problems, these
      technologies can aid in securing the unaffected or "worried well". We also
      highlight the need for public/private partnerships to engage in some of the
      underpinning sciences, such as patho-physiological mechanisms of chemical and
      radiological hazards, and for the necessary investment in the development of
      rapid assessment tools through identification of biochemical, molecular, and
      genetic biomarkers to predict health effects. For chemical agents, biomarkers of
      neurotoxicity, lung damage, and clinical and epidemiological databases are needed
      to assess acute and chronic effects of exposures. For radiological exposures,
      development of rapid, sensitive biomarkers using advanced biotechnologies are
      needed to sort exposed persons at risk of life-threatening effects from persons
      with long-term risk or no risk. The final implementation of rapid and portable
      diagnostics tools suitable for emergency care providers to guide triage and
      medical countermeasures use will need public support, since commercial incentives
      are lacking.

PMID- 22408588
TI  - Controlling access to suicide means.
AB  - BACKGROUND: Restricting access to common means of suicide, such as firearms,
      toxic gas, pesticides and other, has been shown to be effective in reducing rates
      of death in suicide. In the present review we aimed to summarize the empirical
      and clinical literature on controlling the access to means of suicide. METHODS:
      This review made use of both MEDLINE, ISI Web of Science and the Cochrane library
      databases, identifying all English articles with the keywords "suicide means",
      "suicide method", "suicide prediction" or "suicide prevention" and other relevant
      keywords. RESULTS: A number of factors may influence an individual's decision
      regarding method in a suicide act, but there is substantial support that easy
      access influences the choice of method. In many countries, restrictions of access
      to common means of suicide has lead to lower overall suicide rates, particularly
      regarding suicide by firearms in USA, detoxification of domestic and motor
      vehicle gas in England and other countries, toxic pesticides in rural areas,
      barriers at jumping sites and hanging, by introducing "safe rooms" in prisons and
      hospitals. Moreover, decline in prescription of barbiturates and tricyclic
      antidepressants (TCAs), as well as limitation of drugs pack size for paracetamol
      and salicylate has reduced suicides by overdose, while increased prescription of
      SSRIs seems to have lowered suicidal rates. CONCLUSIONS: Restriction to means of
      suicide may be particularly effective in contexts where the method is popular,
      highly lethal, widely available, and/or not easily substituted by other similar
      methods. However, since there is some risk of means substitution, restriction of
      access should be implemented in conjunction with other suicide prevention
      strategies.

PMID- 22408589
TI  - Local heat stroke prevention plans in Japan: characteristics and elements for
      public health adaptation to climate change.
AB  - The adverse health effects from hot weather and heat waves represent significant
      public health risks in vulnerable areas worldwide. Rising temperatures due to
      climate change are aggravating these risks in a context of fast urbanization,
      population growth and societal ageing. However, environmental heat-related health
      effects are largely preventable through adequate preparedness and responses.
      Public health adaptation to climate change will often require the implementation
      of heat wave warning systems and targeted preventive activities at different
      levels. While several national governments have established such systems at the
      country level, municipalities do not generally play a major role in the
      prevention of heat disorders. This paper analyzes selected examples of locally
      operated heat-health prevention plans in Japan. The analysis of these plans
      highlights their strengths, but also the need of local institutions for
      assistance to make the transition towards an effective public health management
      of high temperatures and heat waves. It can also provide useful elements for
      municipal governments in vulnerable areas, both in planning their climate change
      and health adaptation activities or to better protect their communities against
      current health effects from heat.

PMID- 22408590
TI  - Resilience to the health risks of extreme weather events in a changing climate in
      the United States.
AB  - Current public health strategies, policies, and measures are being modified to
      enhance current health protection to climate-sensitive health outcomes. These
      modifications are critical to decrease vulnerability to climate variability, but
      do not necessarily increase resilience to future (and different) weather
      patterns. Communities resilient to the health risks of climate change anticipate
      risks; reduce vulnerability to those risks; prepare for and respond quickly and
      effectively to threats; and recover faster, with increased capacity to prepare
      for and respond to the next threat. Increasing resilience includes top-down
      (e.g., strengthening and maintaining disaster risk management programs) and
      bottom-up (e.g., increasing social capital) measures, and focuses not only on the
      risks presented by climate change but also on the underlying socioeconomic,
      geographic, and other vulnerabilities that affect the extent and magnitude of
      impacts. Three examples are discussed of public health programs designed for
      other purposes that provide opportunities for increasing the capacity of
      communities to avoid, prepare for, and effectively respond to the health risks of
      extreme weather and climate events. Incorporating elements of adaptive management
      into public health practice, including a strong and explicit focus on iteratively
      managing risks, will increase effective management of climate change risks.

PMID- 22408591
TI  - Related factors of insulin resistance in Korean children: adiposity and maternal
      insulin resistance.
AB  - Increased adiposity and unhealthy lifestyle augment the risk for type 2 diabetes
      in children with familial predisposition. Insulin resistance (IR) is an excellent
      clinical marker for identifying children at high risk for type 2 diabetes. This
      study was conducted to investigate parental, physiological, behavioral and socio
      economic factors related to IR in Korean children. This study is a cross
      sectional study using data from 111 children aged 7 years and their parents.
      Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated using
      fasting glucose and insulin level as a marker of IR. All children's adiposity
      indices (r = 0.309-0.318, all P-value = 0.001) and maternal levels of fasting
      insulin (r = 0.285, P-value = 0.003) and HOMA-IR (r = 0.290, P-value = 0.002)
      were positively correlated with children's HOMA-IR level. There was no
      statistical difference of children's HOMA-IR level according to children's
      lifestyle habits and socioeconomic status of families. An increase of 1
      percentage point in body fat was related to 2.7% increase in children's HOMA-IR
      (P-value < 0.001) and an increase of 1% of maternal level of HOMA-IR was related
      to 0.2% increase in children's HOMA-IR (P-value = 0.002). This study shows that
      children's adiposity and maternal IR are positively associated with children's
      IR.

PMID- 22408592
TI  - An updated algorithm for estimation of pesticide exposure intensity in the
      agricultural health study.
AB  - An algorithm developed to estimate pesticide exposure intensity for use in
      epidemiologic analyses was revised based on data from two exposure monitoring
      studies. In the first study, we estimated relative exposure intensity based on
      the results of measurements taken during the application of the herbicide 2,4
      dichlorophenoxyacetic acid (2,4-D) (n = 88) and the insecticide chlorpyrifos (n =
      17). Modifications to the algorithm weighting factors were based on geometric
      means (GM) of post-application urine concentrations for applicators grouped by
      application method and use of chemically-resistant (CR) gloves. Measurement data
      from a second study were also used to evaluate relative exposure levels
      associated with airblast as compared to hand spray application methods. Algorithm
      modifications included an increase in the exposure reduction factor for use of CR
      gloves from 40% to 60%, an increase in the application method weight for boom
      spray relative to in-furrow and for air blast relative to hand spray, and a
      decrease in the weight for mixing relative to the new weights assigned for
      application methods. The weighting factors for the revised algorithm now
      incorporate exposure measurements taken on Agricultural Health Study (AHS)
      participants for the application methods and personal protective equipment (PPE)
      commonly reported by study participants.

PMID- 22408593
TI  - Heatwave early warning systems and adaptation advice to reduce human health
      consequences of heatwaves.
AB  - INTRODUCTION: With climate change, there has been an increase in the frequency,
      intensity and duration of heatwave events. In response to the devastating
      mortality and morbidity of recent heatwave events, many countries have introduced
      heatwave early warning systems (HEWS). HEWS are designed to reduce the avoidable
      human health consequences of heatwaves through timely notification of prevention
      measures to vulnerable populations. OBJECTIVE: To identify the key
      characteristics of HEWS in European countries to help inform modification of
      current, and development of, new systems and plans. METHODS: We searched the
      internet to identify HEWS policy or government documents for 33 European
      countries and requested information from relevant organizations. We translated
      the HEWS documents and extracted details on the trigger indicators, thresholds
      for action, notification strategies, message intermediaries, communication and
      dissemination strategies, prevention strategies recommended and specified target
      audiences. FINDINGS AND CONCLUSIONS: Twelve European countries have HEWS.
      Although there are many similarities among the HEWS, there also are differences
      in key characteristics that could inform improvements in heatwave early warning
      plans.

PMID- 22408594
TI  - Environmental impacts from pesticide use: a case study of soil fumigation in
      Florida tomato production.
AB  - The search for alternative fumigants has been ongoing since the 1992 Parties of
      the Montreal Protocol classified methyl bromide as a Class I controlled substance
      with an ozone depletion potential (ODP) of 0.7 and destined it for phase-out.
      This paper focuses on the hazards from fumigants proposed as alternatives for pre
      plant soil fumigation in tomato production. We use the Environmental Impact
      Quotient (EIQ) developed by Kovach et al. to estimate the hazards from methyl
      bromide and the proposed alternative fumigants to workers, consumers, beneficial
      arthropods, birds, fish, and bees. Our findings indicate that iodomethane 98/2
      has the lowest EIQ index value and field use rating, and is the alternative with
      the lowest relative risk. Among environmental categories, workers and beneficial
      arthropods experience the highest relative risks from the proposed tomato
      fumigants, and fish and consumers the least risks.

PMID- 22408596
TI  - Individual and public-program adaptation: coping with heat waves in five cities
      in Canada.
AB  - Heat Alert and Response Systems (HARS) are currently undergoing testing and
      implementation in Canada. These programs seek to reduce the adverse health
      effects of heat waves on human health by issuing weather forecasts and warnings,
      informing individuals about possible protections from excessive heat, and
      providing such protections to vulnerable subpopulations and individuals at risk.
      For these programs to be designed effectively, it is important to know how
      individuals perceive the heat, what their experience with heat-related illness
      is, how they protect themselves from excessive heat, and how they acquire
      information about such protections. In September 2010, we conducted a survey of
      households in 5 cities in Canada to study these issues. At the time of the
      survey, these cities had not implemented heat outreach and response systems. The
      study results indicate that individuals' recollections of recent heat wave events
      were generally accurate. About 21% of the sample reported feeling unwell during
      the most recent heat spell, but these illnesses were generally minor. Only in 25
      cases out of 243, these illnesses were confirmed or diagnosed by a health care
      professional. The rate at which our respondents reported heat-related illnesses
      was higher among those with cardiovascular and respiratory illnesses, was higher
      among younger respondents and bore no relationship with the availability of air
      conditioning at home. Most of the respondents indicated that they would not
      dismiss themselves as "not at risk" and that they would cope with excessive heat
      by staying in air conditioned environments and keeping well hydrated. Despite the
      absence of heat outreach and education programs in their city, our respondents at
      least a rough idea of how to take care of themselves. The presence of air
      conditioning and knowledge of cooling centers is location-specific, which
      provides opportunities for targeting HARS interventions.

PMID- 22408595
TI  - The centre for healthy weights--shapedown BC: a family-centered,
      multidisciplinary program that reduces weight gain in obese children over the
      short-term.
AB  - The objective was to conduct a program evaluation of the Centre for Healthy
      Weights-Shapedown BC (CHW-SB), a family-centered, multidisciplinary program for
      obese children, by assessing the change in weight trajectories from program
      intake to completion. Secondary outcomes included changes in clinical,
      biochemical and psychological parameters, and in physical activity (PA) levels.
      The CHW-SB program was evaluated over 10 weeks. Data collection included
      anthropometric, metabolic, PA and psychological measures. Longitudinal mixed
      effects regression was performed to evaluate weight change from Phase 1 (before
      program on waitlist) to Phase 2 (during program). 238 children <18 years of age
      were referred to the program of which 119 were eligible for participation. There
      was a significant decrease in weight trajectory in children following program
      entry. Participants experienced an average .89% monthly increase before program
      entry, compared to a .37% monthly decline afterwards, a drop of 1.26% (p <
      0.0001, 95%CI 1.08 to 1.44). zBMI (2.26 +/- 0.33 to 2.20 +/- 0.36, p < 0.001),
      waist circumference (99 +/- 15.7 to 97 +/- 16 cm, p < 0.0001) and fasting insulin
      (137 +/- 94.8 to 121 +/- 83.4 pmol/L, p < 0.001) also decreased in participants
      who attended the final visit. Significant improvements were seen in all measures
      of PA, self-concept, and anxiety. CHW-SB, a government-funded program, is the
      first obesity-treatment program to be evaluated in Canada. While short-term
      evaluation revealed significant improvements in adiposity, PA, and psychological
      measures, the lack of full follow-up is a limitation in interpreting the clinical
      effectiveness of this program, as drop-out may be associated with lack of success
      in meeting program goals. These data also emphasize the need for ongoing
      evaluation to assess the long-term implications of this unique program and
      ultimately optimize utilization of governmental resources.

PMID- 22408597
TI  - Molecular aspects of dopaminergic neurodegeneration: gene-environment interaction
      in parkin dysfunction.
AB  - Parkinson's disease (PD) is a common neurodegenerative movement disorder that is
      characterized pathologically by a progressive loss of midbrain dopaminergic
      neurons and by protein inclusions, designated Lewy bodies and Lewy neurites. PD
      is one of the most common neurodegenerative diseases, affecting almost 1% of the
      population over 60 years old. Although the symptoms and neuropathology of PD have
      been well characterized, the underlying mechanisms and causes of the disease are
      still not clear. Genetic mutations can provide important clues to disease
      mechanism, but most PD cases are sporadic rather than familial; environmental
      factors have long been suspected to contribute to the disease. Although more than
      90% of PD cases occur sporadically and are thought to be due, in part, to
      oxidative stress and mitochondrial dysfunction, the study of genetic mutations
      has provided great insight into the molecular mechanisms of PD. Furthermore,
      rotenone, a widely used pesticide, and paraquat and maneb cause a syndrome in
      rats and mice that mimics, both behaviorally and neurologically, the symptoms of
      PD. In the current review, we will discuss various aspects of gene-environment
      interaction that lead to progressive dopaminergic neurodegenration, mainly
      focusing on our current finding based on stress-mediated parkin dysfunction.

PMID- 22408598
TI  - Perceptions of heat-susceptibility in older persons: barriers to adaptation.
AB  - The increase in the frequency of very hot weather that is a predicted consequence
      of climate change poses an emerging threat to public health. Extreme heat can be
      harmful to the health of older persons who are known to be amongst the most
      vulnerable in the community. This study aimed to investigate factors influencing
      the ability of older persons to adapt to hot conditions, and barriers to
      adaptation. A qualitative study was conducted in Adelaide, Australia, involving
      focus groups and interviews with stakeholders including key personnel involved in
      aged care, community services, government sectors, emergency services and policy
      making. Findings revealed a broad range of factors that underpin the heat
      susceptibility of the aged. These were categorized into four broad themes
      relating to: physiology and an age-related decline in health; socioeconomic
      factors, particularly those influencing air conditioning use; psychological
      issues including fears and anxieties about extreme heat; and adaptive strategies
      that could be identified as both enablers and barriers. As a consequence, the
      ability and willingness to undertake behavior change during heatwaves can
      therefore be affected in older persons. Additionally, understanding the control
      panels on modern air conditioners can present challenges for the aged. Improving
      heat-health knowledge and addressing the social and economic concerns of the
      older population will assist in minimizing heat-related morbidity and mortality
      in a warming climate.

PMID- 22408599
TI  - Determining the maximum cumulative ratios for mixtures observed in ground water
      wells used as drinking water supplies in the United States.
AB  - The maximum cumulative ratio (MCR) developed in previous work is a tool to
      evaluate the need to perform cumulative risk assessments. MCR is the ratio of the
      cumulative exposures to multiple chemicals to the maximum exposure from one of
      the chemicals when exposures are described using a common metric. This tool is
      used to evaluate mixtures of chemicals measured in samples of untreated ground
      water as source for drinking water systems in the United States. The mixtures of
      chemicals in this dataset differ from those examined in our previous work both in
      terms of the predicted toxicity and compounds measured. Despite these
      differences, MCR values in this study follow patterns similar to those seen
      earlier. MCR values for the mixtures have a mean (range) of 2.2 (1.03-5.4) that
      is much smaller than the mean (range) of 16 (5-34) in the mixtures in previous
      study. The MCR values of the mixtures decline as Hazard Index (HI) values
      increase. MCR values for mixtures with larger HI values are not affected by
      possible contributions from chemicals that may occur at levels below the
      detection limits. This work provides a second example of use of the MCR tool in
      the evaluation of mixtures that occur in the environment.

PMID- 22408600
TI  - Biodegradable Magnesium Alloys: A Review of Material Development and
      Applications.
AB  - Magnesium based alloys possess a natural ability to biodegrade due to corrosion
      when placed within aqueous substances, which is promising for cardiovascular and
      orthopedic medical device applications. These materials can serve as a temporary
      scaffold when placed in vivo, which is desirable for treatments when temporary
      supportive structures are required to assist in the wound healing process. The
      nature of these materials to degrade is attributed to the high oxidative
      corrosion rates of magnesium. In this review, a summary is presented for
      magnesium material development, biocorrosion characteristics, as well as a
      biological translation for these results.

PMID- 22408601
TI  - Decoding Finger Movements from ECoG Signals Using Switching Linear Models.
AB  - One of the most interesting challenges in ECoG-based Brain-Machine Interface is
      movement prediction. Being able to perform such a prediction paves the way to
      high-degree precision command for a machine such as a robotic arm or robotic
      hands. As a witness of the BCI community increasing interest toward such a
      problem, the fourth BCI Competition provides a dataset which aim is to predict
      individual finger movements from ECoG signals. The difficulty of the problem
      relies on the fact that there is no simple relation between ECoG signals and
      finger movements. We propose in this paper, to estimate and decode these finger
      flexions using switching models controlled by an hidden state. Switching models
      can integrate prior knowledge about the decoding problem and helps in predicting
      fine and precise movements. Our model is thus based on a first block which
      estimates which finger is moving and another block which, knowing which finger is
      moving, predicts the movements of all other fingers. Numerical results that have
      been submitted to the Competition show that the model yields high decoding
      performances when the hidden state is well estimated. This approach achieved the
      second place in the BCI competition with a correlation measure between real and
      predicted movements of 0.42.

PMID- 22408602
TI  - The hormonal Zeitgeber melatonin: role as a circadian modulator in memory
      processing.
AB  - The neuroendocrine substance melatonin is a hormone synthesized rhythmically by
      the pineal gland under the influence of the circadian system and alternating
      light/dark cycles. Melatonin has been shown to have broad applications, and
      consequently becoming a molecule of great controversy. Undoubtedly, however,
      melatonin plays an important role as a time cue for the endogenous circadian
      system. This review focuses on melatonin as a regulator in the circadian
      modulation of memory processing. Memory processes (acquisition, consolidation,
      and retrieval) are modulated by the circadian system. However, the mechanism by
      which the biological clock is rhythmically influencing cognitive processes
      remains unknown. We also discuss, how the circadian system by generating cycling
      melatonin levels can implant information about daytime into memory processing,
      depicted as day and nighttime differences in acquisition, memory consolidation
      and/or retrieval.

PMID- 22408603
TI  - Synergetic effect of recoverin and calmodulin on regulation of rhodopsin kinase.
AB  - Phosphorylation of photoactivated rhodopsin by rhodopsin kinase (RK or GRK1), a
      first step of the phototransduction cascade turnoff, is under the control of
      Ca(2+)/recoverin. Here, we demonstrate that calmodulin, a ubiquitous Ca(2+)
      sensor, can inhibit RK, though less effectively than recoverin does. We have
      utilized the surface plasmon resonance technology to map the calmodulin binding
      site in the RK molecule. Calmodulin does not interact with the recoverin-binding
      site within amino acid residues M1-S25 of the enzyme. Instead, the high affinity
      calmodulin binding site is localized within a stretch of amino acid residues V150
      K175 in the N-terminal regulatory region of RK. Moreover, the inhibitory effect
      of calmodulin and recoverin on RK activity is synergetic, which is in agreement
      with the existence of separate binding sites for each Ca(2+)-sensing protein. The
      synergetic inhibition of RK by both Ca(2+)-sensors occurs over a broader range of
      Ca(2+)-concentration than by recoverin alone, indicating increased Ca(2+)
      sensitivity of RK regulation in the presence of both Ca(2+)-sensors. Taken
      together, our data suggest that RK regulation by calmodulin in photoreceptor
      cells could complement the well-known inhibitory effect of recoverin on RK.

PMID- 22408604
TI  - Physiology of quantal norepinephrine release from somatodendritic sites of
      neurons in locus coeruleus.
AB  - Norepinephrine (NE) released from the nerve terminal of locus coeruleus (LC)
      neurons contributes to about 70% of the total extracellular NE in primates brain.
      In addition, LC neurons also release NE from somatodendritic sites. Quantal NE
      release from soma of LC neurons has the characteristics of long latency, nerve
      activity-dependency, and autoinhibition by alpha(2)-adrenergic autoreceptor. The
      distinct kinetics of stimulus-secretion coupling in somata is regulated by action
      potential patterns. The physiological significance of soma and dendritic release
      is to produce negative-feedback and to down-regulate neuronal hyperactivity,
      which consequently inhibit NE release from axon terminal of LC projecting to many
      brain areas. Recent discoveries about the LC somatodendritic release may provide
      new insights into the pathogenesis of clinic disease involving LC-NE system
      dysfunction, and may help developing remedy targeted to the LC area.

PMID- 22408605
TI  - The cytochrome c gene proximal enhancer drives activity-dependent reporter gene
      expression in hippocampal neurons.
AB  - The proximal enhancer of the cytochrome c gene (Cycs) contains binding sites for
      both cAMP response element binding proteins (CREB) and Nuclear Respiratory Factor
      1 (NRF1). To investigate how neuronal activity regulates this enhancer region, a
      lentivirus was constructed in which a short-lived green fluorescent protein (GFP)
      was placed under the transcriptional control of the Cycs proximal enhancer linked
      to a synthetic core promoter. Primary hippocampal neurons were infected, and the
      synaptic strengths of individual neurons were measured by whole-cell patch
      clamping. On average the amplitude of miniature postsynaptic currents (mEPSCs)
      was higher in brighter GFP(+) neurons, while the frequency of mEPSCs was not
      significantly different. Inhibiting neural activity by applying a GABAA receptor
      agonist increased GFP expression in most neurons, which persisted after
      homeostatic synaptic scaling as evidenced by a decrease in the amplitude and
      frequency of mEPSCs. Removing the CREB binding sites revealed that calcium influx
      through L-type channels and NMDA receptors, and ERK1/2 activation played a role
      in NRF1-mediated transcription. CREB and NRF1, therefore, combine to regulate
      transcription of Cycs in response to changing neural activity.

PMID- 22408606
TI  - Midbrain dopaminergic neurons generate calcium and sodium currents and release
      dopamine in the striatum of pups.
AB  - Midbrain dopaminergic neurons (mDA neurons) are essential for the control of
      diverse motor and cognitive behaviors. However, our understanding of the activity
      of immature mDA neurons is rudimentary. Rodent mDA neurons migrate and
      differentiate early in embryonic life and dopaminergic axons enter the striatum
      and contact striatal neurons a few days before birth, but when these are
      functional is not known. Here, we recorded Ca(2+) transients and Na(+) spikes
      from embryonic (E16-E18) and early postnatal (P0-P7) mDA neurons with dynamic two
      photon imaging and patch clamp techniques in slices from tyrosine hydroxylase-GFP
      mice, and measured evoked dopamine release in the striatum with amperometry. We
      show that half of identified E16-P0 mDA neurons spontaneously generate non
      synaptic, intrinsically driven Ca(2+) spikes and Ca(2+) plateaus mediated by N-
      and L-type voltage-gated Ca(2+) channels. Starting from E18-P0, half of the mDA
      neurons also reliably generate overshooting Na(+) spikes with an abrupt
      maturation at birth (P0 = E19). At that stage (E18-P0), dopaminergic terminals
      release dopamine in a calcium-dependent manner in the striatum in response to
      local stimulation. This suggests that mouse striatal dopaminergic synapses are
      functional at birth.

PMID- 22408607
TI  - Dynamic regulation of NMDAR function in the adult brain by the stress hormone
      corticosterone.
AB  - Stress and corticosteroids dynamically modulate the expression of synaptic
      plasticity at glutamatergic synapses in the developed brain. Together with alpha
      amino-3-hydroxy-methyl-4-isoxazole propionic acid receptors (AMPAR), N-methyl-D
      aspartate receptors (NMDAR) are critical mediators of synaptic function and are
      essential for the induction of many forms of synaptic plasticity. Regulation of
      NMDAR function by cortisol/corticosterone (CORT) may be fundamental to the
      effects of stress on synaptic plasticity. Recent reports of the efficacy of NMDAR
      antagonists in treating certain stress-associated psychopathologies further
      highlight the importance of understanding the regulation of NMDAR function by
      CORT. Knowledge of how corticosteroids regulate NMDAR function within the adult
      brain is relatively sparse, perhaps due to a common belief that NMDAR function is
      stable in the adult brain. We review recent results from our laboratory and
      others demonstrating dynamic regulation of NMDAR function by CORT in the adult
      brain. In addition, we consider the issue of how differences in the early life
      environment may program differential sensitivity to modulation of NMDAR function
      by CORT and how this may influence synaptic function during stress. Findings from
      these studies demonstrate that NMDAR function in the adult hippocampus remains
      sensitive to even brief exposures to CORT and that the capacity for modulation of
      NMDAR may be programmed, in part, by the early life environment. Modulation of
      NMDAR function may contribute to dynamic regulation of synaptic plasticity and
      adaptation in the face of stress, however, enhanced NMDAR function may be
      implicated in mechanisms of stress-related psychopathologies including
      depression.

PMID- 22408608
TI  - Developmental disorders of the midbrain and hindbrain.
AB  - Malformations of the midbrain (MB) and hindbrain (HB) have become topics of
      considerable interest in the neurology and neuroscience literature in recent
      years. The combined advances of imaging and molecular biology have improved
      analyses of structures in these areas of the central nervous system, while
      advances in genetics have made it clear that malformations of these structures
      are often associated with dysfunction or malformation of other organ systems.
      This review focuses upon the importance of communication between clinical
      researchers and basic scientists in the advancement of knowledge of this group of
      disorders. Disorders of anteroposterior (AP) patterning, cerebellar hypoplasias,
      disorders associated with defects of the pial limiting membrane (cobblestone
      cortex), disorders of the Reelin pathway, and disorders of the primary
      cilium/basal body organelle (molar tooth malformations) are the main focus of the
      review.

PMID- 22408609
TI  - Prediction of Task-Related BOLD fMRI with Amplitude Signatures of Resting-State
      fMRI.
AB  - Blood oxygen contrast-functional magnetic resonance imaging (fMRI) signals are a
      convolution of neural and vascular components. Several studies indicate that task
      related (T-fMRI) or resting-state (R-fMRI) responses linearly relate to
      hypercapnic task responses. Based on the linearity of R-fMRI and T-fMRI with
      hypercapnia demonstrated by different groups using different study designs, we
      hypothesized that R-fMRI and T-fMRI signals are governed by a common
      physiological mechanism and that resting-state fluctuation of amplitude (RSFA)
      should be linearly related to T-fMRI responses. We tested this prediction in a
      group of healthy younger humans where R-fMRI, T-fMRI, and hypercapnic (breath
      hold, BH) task measures were obtained form the same scan session during resting
      state and during performance of motor and BH tasks. Within individual subjects,
      significant linear correlations were observed between motor and BH task responses
      across voxels. When averaged over the whole brain, the subject-wise correlation
      between the motor and BH tasks showed a similar linear relationship within the
      group. Likewise, a significant linear correlation was observed between motor-task
      activity and RSFA across voxels and subjects. The linear rest-task (R-T)
      relationship between motor activity and RSFA suggested that R-fMRI and T-fMRI
      responses are governed by similar physiological mechanisms. A practical use of
      the R-T relationship is its potential to estimate T-fMRI responses in special
      populations unable to perform tasks during fMRI scanning. Using the R-T
      relationship determined from the first group of 12 healthy subjects, we predicted
      the T-fMRI responses in a second group of 7 healthy subjects. RSFA in both the
      lower and higher frequency ranges robustly predicted the magnitude of T-fMRI
      responses at the subject and voxel levels. We propose that T-fMRI responses are
      reliably predictable to the voxel level in situations where only R-fMRI measures
      are possible, and may be useful for assessing neural activity in task non
      compliant clinical populations.

PMID- 22408610
TI  - Dissecting Altered Functional Engagement in TBI and Other Patient Groups through
      Connectivity Analysis: One Goal, Many Paths (A Response to Hillary).

PMID- 22408611
TI  - Tinnitus: pathology of synaptic plasticity at the cellular and system levels.
AB  - Despite being more and more common, and having a high impact on the quality of
      life of sufferers, tinnitus does not yet have a cure. This has been mostly the
      result of limited knowledge of the biological mechanisms underlying this adverse
      pathology. However, the last decade has witnessed tremendous progress in our
      understanding on the pathophysiology of tinnitus. Animal models have demonstrated
      that tinnitus is a pathology of neural plasticity, and has two main components: a
      molecular, peripheral component related to the initiation phase of tinnitus; and
      a system-level, central component-related to the long-term maintenance of
      tinnitus. Using the most recent experimental data and the molecular/system
      dichotomy as a framework, we describe here the biological basis of tinnitus. We
      then discuss these mechanisms from an evolutionary perspective, highlighting
      similarities with memory. Finally, we consider how these discoveries can
      translate into therapies, and we suggest operative strategies to design new and
      effective combined therapeutic solutions using both pharmacological (local and
      systemic) and behavioral tools (e.g., using tele-medicine and virtual reality
      settings).

PMID- 22408613
TI  - Testing the limits of optimizing dual-task performance in younger and older
      adults.
AB  - Impaired dual-task performance in younger and older adults can be improved with
      practice. Optimal conditions even allow for a (near) elimination of this
      impairment in younger adults. However, it is unknown whether such (near)
      elimination is the limit of performance improvements in older adults. The present
      study tests this limit in older adults under conditions of (a) a high amount of
      dual-task training and (b) training with simplified component tasks in dual-task
      situations. The data showed that a high amount of dual-task training in older
      adults provided no evidence for an improvement of dual-task performance to the
      optimal dual-task performance level achieved by younger adults. However, training
      with simplified component tasks in dual-task situations exclusively in older
      adults provided a similar level of optimal dual-task performance in both age
      groups. Therefore through applying a testing the limits approach, we demonstrated
      that older adults improved dual-task performance to the same level as younger
      adults at the end of training under very specific conditions.

PMID- 22408615
TI  - Cellular and circuit mechanisms maintain low spike co-variability and enhance
      population coding in somatosensory cortex.
AB  - The responses of cortical neurons are highly variable across repeated
      presentations of a stimulus. Understanding this variability is critical for
      theories of both sensory and motor processing, since response variance affects
      the accuracy of neural codes. Despite this influence, the cellular and circuit
      mechanisms that shape the trial-to-trial variability of population responses
      remain poorly understood. We used a combination of experimental and computational
      techniques to uncover the mechanisms underlying response variability of
      populations of pyramidal (E) cells in layer 2/3 of rat whisker barrel cortex.
      Spike trains recorded from pairs of E-cells during either spontaneous activity or
      whisker deflected responses show similarly low levels of spiking co-variability,
      despite large differences in network activation between the two states. We
      developed network models that show how spike threshold non-linearities dilute E
      cell spiking co-variability during spontaneous activity and low velocity whisker
      deflections. In contrast, during high velocity whisker deflections, cancelation
      mechanisms mediated by feedforward inhibition maintain low E-cell pairwise co
      variability. Thus, the combination of these two mechanisms ensure low E-cell
      population variability over a wide range of whisker deflection velocities.
      Finally, we show how this active decorrelation of population variability leads to
      a drastic increase in the population information about whisker velocity. The
      prevalence of spiking non-linearities and feedforward inhibition in the nervous
      system suggests that the mechanisms for low network variability presented in our
      study may generalize throughout the brain.

PMID- 22408614
TI  - Non-pharmacological intervention for memory decline.
AB  - Non-pharmacological intervention of memory difficulties in healthy older adults,
      as well as those with brain damage and neurodegenerative disorders, has gained
      much attention in recent years. The two main reasons that explain this growing
      interest in memory rehabilitation are the limited efficacy of current drug
      therapies and the plasticity of the human central nervous and the discovery that
      during aging, the connections in the brain are not fixed but retain the capacity
      to change with learning. Moreover, several studies have reported enhanced
      cognitive performance in patients with neurological disease, following non
      invasive brain stimulation [i.e., repetitive transcranial magnetic stimulation
      and transcranial direct current stimulation to specific cortical areas]. The
      present review provides an overview of memory rehabilitation in individuals with
      mild cognitive impairment and in patients with Alzheimer's disease with
      particular regard to cognitive rehabilitation interventions focused on memory and
      non-invasive brain stimulation. Reviewed data suggest that in patients with
      memory deficits, memory intervention therapy could lead to performance
      improvements in memory, nevertheless further studies need to be conducted in
      order to establish the real value of this approach.

PMID- 22408616
TI  - Gait Modulation in C. elegans: An Integrated Neuromechanical Model.
AB  - Equipped with its 302-cell nervous system, the nematode Caenorhabditis elegans
      adapts its locomotion in different environments, exhibiting so-called swimming in
      liquids and crawling on dense gels. Recent experiments have demonstrated that the
      worm displays the full range of intermediate behaviors when placed in
      intermediate environments. The continuous nature of this transition strongly
      suggests that these behaviors all stem from modulation of a single underlying
      mechanism. We present a model of C. elegans forward locomotion that includes a
      neuromuscular control system that relies on a sensory feedback mechanism to
      generate undulations and is integrated with a physical model of the body and
      environment. We find that the model reproduces the entire swim-crawl transition,
      as well as locomotion in complex and heterogeneous environments. This is achieved
      with no modulatory mechanism, except via the proprioceptive response to the
      physical environment. Manipulations of the model are used to dissect the proposed
      pattern generation mechanism and its modulation. The model suggests a possible
      role for GABAergic D-class neurons in forward locomotion and makes a number of
      experimental predictions, in particular with respect to non-linearities in the
      model and to symmetry breaking between the neuromuscular systems on the ventral
      and dorsal sides of the body.

PMID- 22408612
TI  - Developmental neuroscience of time and number: implications for autism and other
      neurodevelopmental disabilities.
AB  - Estimations of time and number share many similarities in both non-humans and
      man. The primary focus of this review is on the development of time and number
      sense across infancy and childhood, and neuropsychological findings as they
      relate to time and number discrimination in infants and adults. Discussion of
      these findings is couched within a mode-control model of timing and counting
      which assumes time and number share a common magnitude representation system. A
      basic sense of time and number likely serves as the foundation for advanced
      numerical and temporal competence, and aspects of higher cognition-this will be
      discussed as it relates to typical childhood, and certain developmental
      disorders, including autism spectrum disorder. Directions for future research in
      the developmental neuroscience of time and number (NEUTIN) will also be
      highlighted.

PMID- 22408617
TI  - Modeling invariant object processing based on tight integration of simulated and
      empirical data in a Common Brain Space.
AB  - Recent advances in Computer Vision and Experimental Neuroscience provided
      insights into mechanisms underlying invariant object recognition. However, due to
      the different research aims in both fields models tended to evolve independently.
      A tighter integration between computational and empirical work may contribute to
      cross-fertilized development of (neurobiologically plausible) computational
      models and computationally defined empirical theories, which can be incrementally
      merged into a comprehensive brain model. After reviewing theoretical and
      empirical work on invariant object perception, this article proposes a novel
      framework in which neural network activity and measured neuroimaging data are
      interfaced in a common representational space. This enables direct quantitative
      comparisons between predicted and observed activity patterns within and across
      multiple stages of object processing, which may help to clarify how high-order
      invariant representations are created from low-level features. Given the advent
      of columnar-level imaging with high-resolution fMRI, it is time to capitalize on
      this new window into the brain and test which predictions of the various object
      recognition models are supported by this novel empirical evidence.

PMID- 22408618
TI  - The brain's supply and demand in obesity.
AB  - During psychosocial stress, the brain demands extra energy from the body to
      satisfy its increased needs. For that purpose it uses a mechanism referred to as
      "cerebral insulin suppression" (CIS). Specifically, activation of the stress
      system suppresses insulin secretion from pancreatic beta-cells, and in this way
      energy-particularly glucose-is allocated to the brain rather than the periphery.
      It is unknown, however, how the brain of obese humans organizes its supply and
      demand during psychosocial stress. To answer this question, we examined 20 obese
      and 20 normal weight men in two sessions (Trier Social Stress Test and non-stress
      control condition followed by either a rich buffet or a meager salad). Blood
      samples were continuously taken and subjects rated their vigilance and mood by
      standard questionnaires. First, we found a low reactive stress system in obesity.
      While obese subjects showed a marked hormonal response to the psychosocial
      challenge, the cortisol response to the subsequent meal was absent. Whereas the
      brains of normal weight subjects demanded for extra energy from the body by using
      CIS, CIS was not detectable in obese subjects. Our findings suggest that the
      absence of CIS in obese subjects is due to the absence of their meal-related
      cortisol peak. Second, normal weight men were high reactive during psychosocial
      stress in changing their vigilance, thereby increasing their cerebral energy
      need, whereas obese men were low reactive in this respect. Third, normal weight
      subjects preferred carbohydrates after stress to supply their brain, while obese
      men preferred fat and protein instead. We conclude that the brain of obese people
      organizes its need, supply, and demand in a low reactive manner.

PMID- 22408619
TI  - Metabolic studies in brain slices - past, present, and future.

PMID- 22408620
TI  - Sirtuins as regulators of the yeast metabolic network.
AB  - There is growing evidence that the metabolic network is an integral regulator of
      cellular physiology. Dynamic changes in metabolite concentrations, metabolic
      flux, or network topology act as reporters of biological or environmental
      signals, and are required for the cell to trigger an appropriate biological
      reaction. Changes in the metabolic network are recognized by specific sensory
      macromolecules and translated into a transcriptional or translational response.
      The protein family of sirtuins, discovered more than 30 years ago as regulators
      of silent chromatin, seems to fulfill the role of a metabolic sensor during aging
      and conditions of caloric restriction. The archetypal sirtuin, yeast
      silentinformationregulator2 (SIR2), is an NAD(+) dependent protein deacetylase
      that interacts with metabolic enzymes glyceraldehyde-3-phosphate dehydrogenase
      and alcohol dehydrogenase, as well as enzymes involved in NAD(H) synthesis, that
      provide or deprive NAD(+) in its close proximity. This influences sirtuin
      activity, and facilitates a dynamic response of the metabolic network to changes
      in metabolism with effects on physiology and aging. The molecular network
      downstream Sir2, however, is complex. In just two orders, Sir2's metabolism
      related interactions span half of the yeast proteome, and are connected with
      virtually every physiological process. Thus, although it is fundamental to
      analyze single molecular mechanisms, it is at the same time crucial to consider
      this genome-scale complexity when correlating single molecular events with
      complex phenotypes such as aging, cell growth, or stress resistance.

PMID- 22408621
TI  - Aspects of innate immunity and Parkinson's disease.
AB  - Genetic studies on PARK genes have identified dysfunction in proteasomal,
      lysosomal, and mitochondrial enzymes as pathogenic for Parkinson's disease (PD).
      We review the role of these and similar enzymes in mediating innate immune
      signaling. In particular, we have identified that a number of PARK gene products
      as well as other enzymes have roles in innate immune signaling as well as DNA
      repair and regulation, ubiquitination, mitochondrial functioning, and synaptic
      trafficking. PD enzymatic dysfunction is likely to contribute to inadequate
      innate immune responses to a variety of extra- and intra-cellular stimuli, with a
      number of the innate immunity related enzymes found in the characteristic Lewy
      body pathology of PD. The decrease in innate immunity in PD is associated with an
      increase in markers of adaptive immunity, and recent GWAS studies have identified
      variants in human leukocyte antigen region as associated with late-onset sporadic
      PD (Hamza et al., 2010; Hill-Burns et al., 2011). Intriguing new data also
      suggest that peripheral immune responses may be involved, giving some potential
      to alleviate such peripheral dysfunction more directly in patients with PD. It is
      now important to identify the cell type specific immune responses contributing to
      the initial changes that occur in PD, as well as to the propagating immune
      responses important for the progression of PD pathology between cells and within
      the brain. Overall, a complex interplay between different types of immunity
      appear to be involved in the underlying pathology of PD.

PMID- 22408622
TI  - Regulation of aldo-keto reductases in human diseases.
AB  - The aldo-keto reductases (AKRs) are a superfamily of NAD(P)H-linked
      oxidoreductases, which reduce aldehydes and ketones to their respective primary
      and secondary alcohols. AKR enzymes are increasingly being recognized to play an
      important role in the transformation and detoxification of aldehydes and ketones
      generated during drug detoxification and xenobiotic metabolism. Many
      transcription factors have been identified to regulate the expression of human
      AKR genes, which could have profound effects on the metabolism of endogenous
      mediators and detoxication of chemical carcinogens. This review summarizes the
      current knowledge on AKR regulation by transcription factors and other mediators
      in human diseases.

PMID- 22408623
TI  - Bilirubin: An Endogenous Molecule with Antiviral Activity in vitro.
AB  - Bilirubin-IX-alpha (BR) is the final product of heme metabolism through the heme
      oxygenase/biliverdin reductase (HO/BVR) system. Previous papers reported on the
      microbicidal effects of the HO by-products biliverdin-IX-alpha, carbon monoxide
      and iron, through either direct or indirect mechanisms. In this paper the
      evidence of a virucidal effect of BR against human herpes simplex virus type 1
      (HSV-1) and the enterovirus EV71 was provided. Bilirubin-IX-alpha, at
      concentrations 1-10 MUM, close to those found in blood and tissues, significantly
      reduced HSV-1 and EV71 replication in Hep-2 and Vero cell lines, respectively.
      Bilirubin-IX-alpha inhibited viral infection of Hep-2 and Vero cells when given 2
      h before, concomitantly and 2 h after viral infection. Furthermore, BR retained
      its antiviral activity even complexed with a saturating concentration of human
      serum-albumin. Moreover, 10 MUM BR increased the formation of nitric oxide and
      the phosphorylation of c-Jun N-terminal kinase in Vero and Hep-2 cell lines,
      respectively, thus implying a role of these two pathways in the mechanism of
      antiviral activity of the bile pigment. In conclusion, these results support the
      antiviral effect of BR against HSV-1 and enterovirus in vitro, and put the basis
      for further basic and clinical studies to understand the real role of BR as an
      endogenous antiviral molecule.

PMID- 22408624
TI  - Apolipoprotein mimetic peptides: a new approach for the treatment of asthma.
AB  - New treatments are needed for severe asthmatics to improve disease control and
      avoid severe toxicities associated with oral corticosteroids. We have used a
      murine model of house dust mite (HDM)-induced asthma to identify steroid
      unresponsive genes that might represent targets for new therapeutic approaches
      for severe asthma. This strategy identified apolipoprotein E as a steroid
      unresponsive gene with increased mRNA expression in the lungs of HDM-challenged
      mice. Furthermore, apolipoprotein E functioned as an endogenous negative
      regulator of airway hyperreactivity and goblet cell hyperplasia in experimental
      HDM-induced asthma. The ability of apolipoprotein E, which is expressed by lung
      macrophages, to attenuate AHR, and goblet cell hyperplasia is mediated by low
      density lipoprotein (LDL) receptors expressed by airway epithelial cells.
      Consistent with this, administration of an apolipoprotein E mimetic peptide,
      corresponding to amino acids 130-149 of the LDL receptor-binding domain of the
      holo-apoE protein, significantly reduced AHR and goblet cell hyperplasia in HDM
      challenged apoE(-/-) mice. These findings identified the apolipoprotein E - LDL
      receptor pathway as a new druggable target for asthma that can be activated by
      administration of apoE-mimetic peptides. Similarly, apolipoprotein A-I may have
      therapeutic potential in asthma based upon its anti-inflammatory, anti-oxidative,
      and anti-fibrotic properties. Furthermore, administration of apolipoprotein A-I
      mimetic peptides has attenuated airway inflammation, airway remodeling, and
      airway hyperreactivity in murine models of experimental asthma. Thus, site
      directed delivery of inhaled apolipoprotein E or apolipoprotein A-I mimetic
      peptides may represent novel treatment approaches that can be developed for
      asthma, including severe disease.

PMID- 22408625
TI  - Bile pigments in pulmonary and vascular disease.
AB  - The bile pigments, biliverdin, and bilirubin, are endogenously derived substances
      generated during enzymatic heme degradation. These compounds have been shown to
      act as chemical antioxidants in vitro. Bilirubin formed in tissues circulates in
      the serum, prior to undergoing hepatic conjugation and biliary excretion. The
      excess production of bilirubin has been associated with neurotoxicity, in
      particular to the newborn. Nevertheless, clinical evidence suggests that mild
      states of hyperbilirubinemia may be beneficial in protecting against
      cardiovascular disease in adults. Pharmacological application of either bilirubin
      and/or its biological precursor biliverdin, can provide therapeutic benefit in
      several animal models of cardiovascular and pulmonary disease. Furthermore,
      biliverdin and bilirubin can confer protection against ischemia/reperfusion
      injury and graft rejection secondary to organ transplantation in animal models.
      Several possible mechanisms for these effects have been proposed, including
      direct antioxidant and scavenging effects, and modulation of signaling pathways
      regulating inflammation, apoptosis, cell proliferation, and immune responses. The
      practicality and therapeutic-effectiveness of bile pigment application to humans
      remains unclear.

PMID- 22408627
TI  - Low- vs High-Frequency Repetitive Transcranial Magnetic Stimulation as an Add-On
      Treatment for Refractory Depression.
AB  - OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) seems to be
      effective as an antidepressant, however, some confusion remains about the best
      parameters to apply and the efficacy of its association with pharmacological
      antidepressant treatments. METHOD: In a single blind randomized study 14 patients
      with unipolar resistant depression to one antidepressant treatment were enrolled
      to receive, in combination with venlafaxine (150 mg), either 20 sessions of 10 Hz
      rTMS (2000 pulses per session) applied over the left dorsolateral prefrontal
      cortex (DLPFC) or 20 sessions of 1 Hz rTMS (120 stimulations per sessions)
      applied over the right DLPFC. RESULTS: A similar antidepressant effect was
      observed in both groups with a comparable antidepressant delay of action (2
      weeks) and a comparable number of responders (MADRS < 15) after 4 weeks of daily
      rTMS sessions (66 vs 50%). CONCLUSION: Low- and high- frequency rTMS seems to be
      effective as an add-on treatment to venlafaxine as monotherapy in pharmacological
      refractory major depression (stage 1). Due to its short duration (one session of
      1 Hz rTMS lasts 4 min vs 16 for 10 Hz rTMS) and its safety, low frequency rTMS
      may be a useful alternative treatment for patients with refractory depression.

PMID- 22408626
TI  - Microglial activation - tuning and pruning adult neurogenesis.
AB  - NEW NEURONS ARE CONTINUOUSLY GENERATED IN TWO ADULT BRAIN REGIONS: the
      subgranular zone of the hippocampus and the subependyma by the lateral
      ventricles, referred to as the neurogenic niches. During their development from
      neural stem cells to mature functionally integrated neurons numerous choices are
      made, such as proliferation or quiescence, cell survival or death, migration or
      establishment, growth or retraction of processes, synaptic assembly or pruning,
      or tuning of synaptic transmission. The process is altered by physiological
      stimuli as well as several brain diseases. Microglia are located within the
      neurogenic niches and have become interesting candidates for modulating
      neurogenesis in both the healthy and injured brain. They become activated by
      foreign antigens or changes in the brain homeostasis and transform this innate
      immunity into an adaptive immune response by recruiting systemic immune cells.
      Most studies report an acute decrease in the survival of new neurons following
      this classically activated microglia reaction. The long-term effects are more
      complex. In neurodegenerative diseases, microglial activation is more
      heterogeneous and the transformation from a pro- to an anti-inflammatory cytokine
      profile and the deactivation of microglia is not well defined. The diversity is
      reflected by numerous reports describing both beneficial and detrimental effects
      on neurogenesis, primarily on the proliferation, survival, and cell fate.
      However, relatively few studies have investigated alterations at later stages of
      neurogenesis including the functional integration. Though likely, it is not
      established how a fine-tuned cross-talk between microglia and adult-born neurons
      would work and how it changes upon microglia activation. This review will
      therefore launch three hypotheses for how microglia might direct synaptic
      integration of newborn neurons, currently a fast expanding research field.

PMID- 22408628
TI  - The Importance of Being Interpreted: Grounded Words and Children's Relational
      Reasoning.
AB  - Although young children typically have trouble reasoning relationally, they are
      aided by the presence of "relational" words (e.g., Gentner and Rattermann, 1991).
      They also reason well about commonly experienced event structures (e.g., Fivush,
      1984). To explore what makes a word "relational" and therefore helpful in
      relational reasoning, we hypothesized that these words activate well-understood
      event structures. Furthermore, the activated schema must be open enough (without
      too much specificity) that it can be applied analogically to novel problems. Four
      experiments examine this hypothesis by exploring: how training with a label
      influence the schematic interpretation of a scene, what kinds of scenes are
      conducive to schematic interpretation, and whether children must figure out the
      interpretation themselves to benefit from the act of interpreting a scene as an
      event. Experiment 1 shows the superiority of schema-evoking words over words that
      do not connect to schematized experiences. Experiments 2 and 3 further reveal
      that these words must be applied to perceptual instances that require cognitive
      effort to connect to a label rather than unrelated or concretely related
      instances in order to draw attention to relational structure. Experiment 4
      provides evidence that even when children do not work out an interpretation for
      themselves, just the act of interpreting an ambiguous scene is potent for
      relational generalization. The present results suggest that relational words (and
      in particular their meanings) are created from the act of interpreting a
      perceptual situation in the context of a word.

PMID- 22408629
TI  - Linguistically modulated perception and cognition: the label-feedback hypothesis.
AB  - How does language impact cognition and perception? A growing number of studies
      show that language, and specifically the practice of labeling, can exert
      extremely rapid and pervasive effects on putatively non-verbal processes such as
      categorization, visual discrimination, and even simply detecting the presence of
      a stimulus. Progress on the empirical front, however, has not been accompanied by
      progress in understanding the mechanisms by which language affects these
      processes. One puzzle is how effects of language can be both deep, in the sense
      of affecting even basic visual processes, and yet vulnerable to manipulations
      such as verbal interference, which can sometimes nullify effects of language. In
      this paper, I review some of the evidence for effects of language on cognition
      and perception, showing that performance on tasks that have been presumed to be
      non-verbal is rapidly modulated by language. I argue that a clearer understanding
      of the relationship between language and cognition can be achieved by rejecting
      the distinction between verbal and non-verbal representations and by adopting a
      framework in which language modulates ongoing cognitive and perceptual processing
      in a flexible and task-dependent manner.

PMID- 22408630
TI  - How Predictable are "Spontaneous Decisions" and "Hidden Intentions"? Comparing
      Classification Results Based on Previous Responses with Multivariate Pattern
      Analysis of fMRI BOLD Signals.
AB  - In two replication studies we examined response bias and dependencies in
      voluntary decisions. We trained a linear classifier to predict "spontaneous
      decisions" and in the second study "hidden intentions" from responses in
      preceding trials and achieved comparable prediction accuracies as reported for
      multivariate pattern classification based on voxel activities in frontopolar
      cortex. We discuss implications of our findings and suggest ways to improve
      classification analyses of fMRI BOLD signals that may help to reduce effects of
      response dependencies between trials.

PMID- 22408631
TI  - Effects of delayed visual feedback on grooved pegboard test performance.
AB  - Using four experiments, this study investigates what amount of delay brings about
      maximal impairment under delayed visual feedback and whether a critical interval,
      such as that in audition, also exists in vision. The first experiment measured
      the Grooved Pegboard test performance as a function of visual feedback delays
      from 120 to 2120 ms in 16 steps. Performance sharply decreased until about 490
      ms, then more gradually until 2120 ms, suggesting that two mechanisms were
      operating under delayed visual feedback. Since delayed visual feedback differs
      from delayed auditory feedback in that the former induces not only temporal but
      also spatial displacements between motor and sensory feedback, this difference
      could also exist in the mechanism responsible for spatial displacement. The
      second experiment was hence conducted to provide simultaneous haptic feedback
      together with delayed visual feedback to inform correct spatial position. The
      disruption was significantly ameliorated when information about spatial position
      was provided from a haptic source. The sharp decrease in performance of up to
      approximately 300 ms was followed by an almost flat performance. This is similar
      to the critical interval found in audition. Accordingly, the mechanism that
      caused the sharp decrease in performance in experiments 1 and 2 was probably
      mainly responsible for temporal disparity and is common across different modality
      motor combinations, while the other mechanism that caused a rather gradual
      decrease in performance in experiment 1 was mainly responsible for spatial
      displacement. In experiments 3 and 4, the reliability of spatial information from
      the haptic source was reduced by wearing a glove or using a tool. When the
      reliability of spatial information was reduced, the data lay between those of
      experiments 1 and 2, and that a gradual decrease in performance partially
      reappeared. These results further support the notion that two mechanisms operate
      under delayed visual feedback.

PMID- 22408632
TI  - Binding "When" and "Where" Impairs Temporal, but not Spatial Recall in Auditory
      and Visual Working Memory.
AB  - Information about where and when events happen seem naturally linked to each
      other, but only few studies have investigated whether and how they are associated
      in working memory. We tested whether the location of items and their temporal
      order are jointly or independently encoded. We also verified if spatio-temporal
      binding is influenced by the sensory modality of items. Participants were
      requested to memorize the location and/or the serial order of five items
      (environmental sounds or pictures sequentially presented from five different
      locations). Next, they were asked to recall either the item location or their
      order of presentation within the sequence. Attention during encoding was
      manipulated by contrasting blocks of trials in which participants were requested
      to encode only one feature to blocks of trials where they had to encode both
      features. Results show an interesting interaction between task and attention.
      Accuracy in serial order recall was affected by the simultaneous encoding of item
      location, whereas the recall of item location was unaffected by the concurrent
      encoding of the serial order of items. This asymmetric influence of attention on
      the two tasks was similar for the auditory and visual modality. Together, these
      data indicate that item location is processed in a relatively automatic fashion,
      whereas maintaining serial order is more demanding in terms of attention. The
      remarkably analogous results for auditory and visual memory performance, suggest
      that the binding of serial order and location in working memory is not modality
      dependent, and may involve common intersensory mechanisms.

PMID- 22408633
TI  - Shared or separate mechanisms for self-face and other-face processing? Evidence
      from adaptation.
AB  - Evidence that self-face recognition is dissociable from general face recognition
      has important implications both for models of social cognition and for our
      understanding of face recognition. In two studies, we examine how adaptation
      affects the perception of personally familiar faces, and we use a visual
      adaptation paradigm to investigate whether the neural mechanisms underlying the
      recognition of one's own and other faces are shared or separate. In Study 1 we
      show that the representation of personally familiar faces is rapidly updated by
      visual experience with unfamiliar faces, so that the perception of one's own face
      and a friend's face is altered by a brief period of adaptation to distorted
      unfamiliar faces. In Study 2, participants adapted to images of their own and a
      friend's face distorted in opposite directions; the contingent aftereffects we
      observe are indicative of separate neural populations, but we suggest that these
      reflect coding of facial identity rather than of the categories "self" and
      "other."

PMID- 22408634
TI  - Physicians' Knowledge of the Glasgow Coma Scale in a Nigerian University
      Hospital: Is the Simple GCS Still Too Complex?
AB  - OBJECTIVE: The Glasgow Coma Scale, GCS, is a universal clinical means of
      quantifying the level of impaired consciousness. Although physicians usually
      receive undergraduate and postgraduate training in the use of this scale in our
      university hospital we are aware of studies suggesting that the working knowledge
      of the GCS among practising physicians might not be adequate. METHODS: We carried
      out a questionnaire-based survey across all specialties and levels of training of
      physicians in active patient care in a Nigerian university hospital. RESULTS: Of
      the 100 physicians sampled, 98 correctly spelled out what the three-letter
      abbreviation, GCS, stands for. Ninety-three percent also conceded it to be an
      important clinical rating scale. However, only 55-89% of the participants
      correctly identified the three respective clinical variables, (eye opening,
      verbal response, and motor response), of the GCS. More particularly, the
      participants' ability to itemize and correctly score all the respective
      components of each of the three clinical variables ranged from 0 to 35% across
      specialties and levels of training. Performance was best for the four-item eye
      opening variable and, worst for the six-item motor response variable. CONCLUSION:
      In our university hospital, practising physicians' working knowledge of the GCS
      is inadequate and is dependent on the degree of the complexity of each of the
      three clinical variables of the scale.

PMID- 22408635
TI  - Perspectives on creating clinically relevant blast models for mild traumatic
      brain injury and post traumatic stress disorder symptoms.
AB  - Military personnel are returning from Iraq and Afghanistan and reporting non
      specific physical (somatic), behavioral, psychological, and cognitive symptoms.
      Many of these symptoms are frequently associated with mild traumatic brain injury
      (mTBI) and/or post traumatic stress disorder (PTSD). Despite significant
      attention and advances in assessment and intervention for these two conditions,
      challenges persist. To address this, clinically relevant blast models are
      essential in the full characterization of this type of injury, as well as in the
      testing and identification of potential treatment strategies. In this
      publication, existing diagnostic challenges and current treatment practices for
      mTBI and/or PTSD will be summarized, along with suggestions regarding how what
      has been learned from existing models of PTSD and traditional mechanism (e.g.,
      non-blast) traumatic brain injury can be used to facilitate the development of
      clinically relevant blast models.

PMID- 22408636
TI  - Revisiting baclofen for the treatment of severe chronic tinnitus.

PMID- 22408638
TI  - Seasonal changes in methanogenesis and methanogenic community in three peatlands,
      new york state.
AB  - Fluctuating environmental conditions can promote diversity and control dominance
      in community composition. In addition to seasonal temperature and moisture
      changes, seasonal supply of metabolic substrates selects populations temporally.
      Here we demonstrate cascading effects in the supply of metabolic substrates on
      methanogenesis and community composition of anaerobic methanogenic archaea in
      three contrasting peatlands in upstate New York. Fresh samples of peat soils,
      collected about every 3 months for 20 months and incubated at 22 +/- 2 degrees C
      regardless of the in situ temperature, exhibited potential rates of methane
      (CH(4)) production of 0.02-0.2 mmol L(-1) day(-1) [380-3800 nmol g(-1) (dry) day(
      1)). The addition of acetate stimulated rates of CH(4) production in a fen
      peatland soil, whereas addition of hydrogen (H(2)), and simultaneous inhibition
      of H(2)-consuming acetogenic bacteria with rifampicin, stimulated CH(4)
      production in two acidic bog soils, especially, in autumn and winter. The
      methanogenic community structure was characterized using T-RFLP analyses of SSU
      rRNA genes. The E2 group of methanogens (Methanoregulaceae) dominated in the two
      acidic bog peatlands with relatively greater abundance in winter. In the fen
      peatland, the E1 group (Methanoregulaceae) and members of the Methanosaetaceae
      were co-dominant, with E1 having a high relative abundance in spring. Change in
      relative abundance profiles among methanogenic groups in response to added
      metabolic substrates was as predicted. The acetate-amendment increased abundance
      of Methanosarcinaceae, and H(2)-amendment enhanced abundance of E2 group in all
      peat soils studied, respectively. Additionally, addition of acetate increased
      abundance of Methanosaetaceae only in the bog soils. Variation in the supply of
      metabolic substrates helps explain the moderate diversity of methanogens in
      peatlands.

PMID- 22408637
TI  - Iron utilization in marine cyanobacteria and eukaryotic algae.
AB  - Iron is essential for aerobic organisms. Additionally, photosynthetic organisms
      must maintain the iron-rich photosynthetic electron transport chain, which likely
      evolved in the iron-replete Proterozoic ocean. The subsequent rise in oxygen
      since those times has drastically decreased the levels of bioavailable iron,
      indicating that adaptations have been made to maintain sufficient cellular iron
      levels in the midst of scarcity. In combination with physiological studies, the
      recent sequencing of marine microorganism genomes and transcriptomes has begun to
      reveal the mechanisms of iron acquisition and utilization that allow marine
      microalgae to persist in iron limited environments.

PMID- 22408639
TI  - Occurrence of CTX-M Producing Escherichia coli in Soils, Cattle, and Farm
      Environment in France (Burgundy Region).
AB  - CTX-M [a major type of extended-spectrum beta-lactamase (ESBL)] producing
      Escherichia coli are increasingly involved in human infections worldwide. The aim
      of this study was to investigate potential reservoirs for such strains: soils,
      cattle, and farm environment. The prevalence of bla(CTX-M) genes was determined
      directly from soil DNA extracts obtained from 120 sites in Burgundy (France)
      using real-time PCR. bla(CTX-M) targets were found in 20% of the DNA extracts
      tested. Samples of cattle feces (n = 271) were collected from 182 farms in
      Burgundy. Thirteen ESBL-producing isolates were obtained from 12 farms and
      further characterized for the presence of bla genes. Of the 13 strains, five and
      eight strains carried bla(TEM-71) genes and bla(CTX-M-1) genes respectively. Ten
      strains of CTX-M-1 producing E. coli were isolated from cultivated and pasture
      soils as well as from composted manure within two of these farms. The genotypic
      analysis revealed that environmental and animal strains were clonally related.
      Our study confirms the occurrence of CTX-M producing E. coli in cattle and
      reports for the first time the occurrence of such strains in cultivated soils.
      The environmental competence of such strains has to be determined and might
      explain their long term survival since CTX-M isolates were recovered from a soil
      that was last amended with manure 1 year before sampling.

PMID- 22408640
TI  - Invasion of Nostocales (cyanobacteria) to Subtropical and Temperate Freshwater
      Lakes - Physiological, Regional, and Global Driving Forces.
AB  - Similar to the increased number of studies on invasive plants and animals in
      terrestrial and aquatic ecosystems, many reports were recently published on the
      invasion of Nostocales (cyanobacteria) to freshwater environments worldwide.
      Invasion and proliferation of Nostocales in new habitats have the potential to
      significantly alter the structure of the native community and to modify ecosystem
      functioning. But most importantly, they influence the water quality due to a
      variety of toxic compounds that some species produce. Therefore a special
      attention was given to the invasion and persistence of toxic cyanobacteria in
      many aquatic ecosystems. Here we summarize the currently published records on the
      invasion of two Nostocales genera, Cylindrospermopsis and Aphanizomenon, to lakes
      and water reservoirs in subtropical and temperate zones. These invading species
      possess traits thought to be common to many invasive organisms: high growth rate,
      high resource utilization efficiency and overall superior competitive abilities
      over native species when local conditions vary. Assuming that dispersion routes
      of cyanobacteria have not been changed much in recent decades, their recent
      establishment and proliferation in new habitats indicate changes in the
      environment under which they can exploit their physiological advantage over the
      native phytoplankton population. In many cases, global warming was identified as
      the major driving force for the invasion of Nostocales. Due to this
      uncontrollable trend, invasive Nostocales species are expected to maintain their
      presence in new habitats and further expand to new environments. In other cases,
      regional changes in nutrient loads and in biotic conditions were attributed to
      the invasion events.

PMID- 22408641
TI  - Chemosensitization of plant pathogenic fungi to agricultural fungicides.
AB  - A common consequence of using agricultural fungicides is the development of
      resistance by fungal pathogens, which undermines reliability of fungicidal
      effectiveness. A potentially new strategy to aid in overcoming or minimizing this
      problem is enhancement of pathogen sensitivity to fungicides, or
      "chemosensitization." Chemosensitization can be accomplished by combining a
      commercial fungicide with a certain non- or marginally fungicidal substance at
      levels where, alone, neither compound would be effective. Chemosensitization
      decreases the probability of the pathogen developing resistance, reduces the
      toxic impact on the environment by lowering effective dosage levels of toxic
      fungicides, and improves efficacy of antifungal agents. The present study shows
      that the antifungal activity of azole and strobilurin fungicides can be
      significantly enhanced through their co-application with certain natural or
      synthetic products against several economically important plant pathogenic fungi.
      Quadris (azoxystrobin) combined with thymol at a non-fungitoxic concentration
      produced much higher growth inhibition of Bipolaris sorokiniana, Phoma glomerata,
      Alternaria sp. and Stagonospora nodorum than the fungicide alone. The effect of
      Dividend (difenoconazole) applied with thymol significantly enhanced antifungal
      activity against B. sorokiniana and S. nodorum. Folicur (tebuconazole) combined
      with 4-hydroxybenzaldehyde (4-HBA), 2,3-dihydroxybenzaldehyde or thymol
      significantly inhibited growth of Alternaria alternata, at a much greater level
      than the fungicide alone. In addition, co-application of Folicur and 4-HBA
      resulted in a similar enhancement of antifungal activity against Fusarium
      culmorum. Lastly, we discovered that metabolites in the culture liquid of
      Fusarium sambucinum biocontrol isolate FS-94 also had chemosensitizing activity,
      increasing S. nodorum sensitivity to Folicur and Dividend.

PMID- 22408642
TI  - Statistical inference and reverse engineering of gene regulatory networks from
      observational expression data.
AB  - In this paper, we present a systematic and conceptual overview of methods for
      inferring gene regulatory networks from observational gene expression data.
      Further, we discuss two classic approaches to infer causal structures and compare
      them with contemporary methods by providing a conceptual categorization thereof.
      We complement the above by surveying global and local evaluation measures for
      assessing the performance of inference algorithms.

PMID- 22408643
TI  - Perspectives of Long Non-Coding RNAs in Cancer Diagnostics.
AB  - Long non-coding RNAs (lncRNAs) transcribed from intergenic and intronic regions
      of the human genome constitute a broad class of cellular transcripts that are
      under intensive investigation. While only a handful of lncRNAs have been
      characterized, their involvement in fundamental cellular processes that control
      gene expression highlights a central role in cell homeostasis. Not surprisingly,
      aberrant expression of regulatory lncRNAs has been increasingly documented in
      different types of cancer, where they can mediate both oncogenic or tumor
      suppressor effects. Interaction with chromatin remodeling complexes that promote
      silencing of specific genes or modulation of splicing factor proteins seem to be
      two general modes of lncRNA regulation, but it is conceivable that additional
      mechanisms of action are yet to be unveiled. LncRNAs show greater tissue
      specificity compared to protein-coding mRNAs making them attractive in the search
      of novel diagnostics/prognostics cancer biomarkers in body fluid samples. In
      fact, lncRNA prostate cancer antigen 3 can be detected in urine samples and has
      been shown to improve diagnosis of prostate cancer. We suggest that an unbiased
      screening of the presence of RNAs in easily accessible body fluids such as serum
      and urine might reveal novel circulating lncRNAs as potential biomarkers in many
      types of cancer. Annotation and functional characterization of the lncRNA
      complement of the cancer transcriptome will conceivably provide new venues for
      early diagnosis and treatment of the disease.

PMID- 22408644
TI  - Design and implementation of an online weekly journal to study unintended
      pregnancies.
AB  - In this article we describe new research to investigate unintended pregnancies
      during the transition to adulthood. The Relationship Dynamics and Social Life
      (RDSL) study begins with a 60-minute in-person interview about family background
      and current relationship characteristics. At the conclusion of the interview,
      respondents are enrolled in an ongoing journal, which consists of a 5-minute
      survey via web or phone and occurs weekly for 2.5 years. We have enrolled over
      1,000 young women in the study and have experienced excellent baseline response
      rates and high journal participation rates. Below we describe the limitations of
      past research on unintended pregnancy as a background for our study. Then we
      provide a detailed description of the study and its design strengths and
      weaknesses.

PMID- 22408645
TI  - Switching of Self-Assembly in a Peptide Nanostructure with a Specific Enzyme.
AB  - Peptide self-assembly has been shown to be a useful tool for the preparation of
      bioactive nanostructures, and recent work has demonstrated their potential as
      therapies for regenerative medicine. In principle, one route to make these
      nanostructures more biomimetic would be to incorporate in their molecular design
      the capacity for biological sensing. We report here on the use of a reversible
      enzymatic trigger to control the assembly and disassembly of peptide amphiphile
      (PA) nanostructures. The PA used in these studies contained a consensus substrate
      sequence specific to protein kinase A (PKA), a biological enzyme important for
      intracellular signaling that has also been shown to be an extracellular cancer
      biomarker. Upon treatment with PKA, this PA molecule becomes phosphorylated
      causing the high aspect-ratio filamentous PA nanostructures to disassemble.
      Treatment with an enzyme to cleave the phosphate group results in reformation of
      the filamentous nanostructures. We also show that disassembly in the presence of
      PKA allows the enzyme-triggered release of an encapsulated cancer drug. In
      addition, these drug-loaded nanostructures were found to induce preferential
      cytotoxicity in a cancer cell line that is known to secrete high levels of PKA.
      This ability to control nanostructure through an enzymatic switch could allow for
      the preparation of highly sophisticated and biomimetic materials that incorporate
      a biological sensing capability to enable therapeutic specificity.

PMID- 22408647
TI  - Myocardial infarction induced by spontaneous pneumothorax.
AB  - Chest pain is a very common condition. Patients may have a benign condition or
      present with a potentially lethal condition such as acute myocardial infarction,
      aortic dissection or tension pneumothorax. It is important to remember that
      patients may present with more than one serious pathology and that other serious
      conditions may potentially precipitate an acute coronary syndrome in a
      susceptible individual. We report the case of an elderly man with a background of
      chronic obstructive pulmonary disease who presented with sudden onset of chest
      pain and severe dyspnoea. Pneumothorax was diagnosed promptly and a chest drain
      inserted. His electrocardiogram (ECG) was abnormal and it is known that ECG
      changes do occur with spontaneous pneumothorax that have on occasions led to the
      incorrect diagnosis of acute myocardial infarction. Our patient had ongoing chest
      pain and it became evident that he also had developed an acute myocardial
      infarction.

PMID- 22408646
TI  - Are Psychiatric Diagnoses an Obstacle for Research and Practice? Reliability,
      Validity and the Problem of Psychiatric Diagnoses. The Case of GAD.
AB  - The present article focused on the problem of validity, reliability and
      specificity of psychiatric diagnoses.The authors moved by the concept of
      syndrome, defined by Sydenham in the 18th century as a constellation of several
      interrelated symptoms, showing a stable, characteristic structure and a peculiar
      prognosis, in order to analyse the peculiarity of the current psychiatric
      nosology. In our opinion, the current nosographic system based on DSM-IV
      criteria, prevents psychiatry from benefiting of the significant technological
      progress that has led the rest of medical sciences to important clinical
      achievements in the last 20 years. The case of Generalized Anxiety Disorder was
      taken as an example of a disease characterized by unstable diagnostic criteria,
      high rate of comorbidity and uncertain boundaries. An analysis of the data from
      the Sesto Fiorentino study was performed to investigate the presence of common
      mood and anxiety symptoms across the most represented DSM IV diagnoses, in order
      to evaluate the specificity of these symptoms.The results supported the
      hypothesis of a low specificity of these symptoms, suggesting the need for
      psychiatry to find new and more specific markers and instruments.

PMID- 22408648
TI  - Metachronous adenocarcinoma in a gastric tube after radical surgery for
      oesophageal cancer.
AB  - In recent years the prognosis for oesophageal squamous cell carcinoma patients
      has improved. Together with this improvement, the occurrence of second primary
      carcinoma, especially gastric carcinoma, in tubes constructed from the stomach
      after oesophagectomy must be taken into account. We report a case of a patient
      who had this clinical presentation, which was revealed not in the normal follow
      up, but in a consecutive operation carried out because of an anastomotic problem.

PMID- 22408649
TI  - Plausible mechanism of small bowel injury during trocar cystostomy.
AB  - An 86-year-old man presented with urinary retention secondary to detrusor failure
      and bulbar urethral stricture. He had a non-tender, palpable, grossly distended
      bladder and a very poor tone in the muscles of the abdominal wall. He did not
      allow urethral or suprapubic catheterisation under local anaesthesia; hence, a
      trocar cystostomy was performed under a short general anaesthesia, which led to
      injury to the small bowel when least expected. We discuss its subsequent
      management and plausible mechanism underlying this unexpected complication in the
      given circumstances.

PMID- 22408650
TI  - A diabetic with recent blindness and paralysis of one eye.

PMID- 22408653
TI  - NON-INVASIVE MEASUREMENT OF DEEP TISSUE TEMPERATURE CHANGES CAUSED BY APOPTOSIS
      DURING BREAST CANCER NEOADJUVANT CHEMOTHERAPY: A CASE STUDY.
AB  - Treatment-induced apoptosis of cancer cells is one goal of cancer therapy.
      Interestingly, more heat is generated by mitochondria during apoptosis,
      especially the uncoupled apoptotic state,(1,2) compared to the resting state. In
      this case study, we explore these thermal effects by longitudinally measuring
      temperature variations in a breast lesion of a pathological complete responder
      during neadjuvant chemotherapy (NAC). Diffuse Optical Spectroscopic Imaging
      (DOSI) was employed to derive absolute deep tissue temperature using subtle
      spectral features of the water peak at 975 nm.3 A significant temperature
      increase was observed in time windows during the anthracycline and
      cyclophosphamide (AC) regimen but in not paclitaxel and bevacizumab regimen.
      Hemoglobin concentration changes generally did not follow temperature, suggesting
      that the measured temperature increases were likely due to mitochondrial
      uncoupling rather than a direct vascular effect. A simultaneous increase of
      tissue oxygen saturation with temperature was also observed, suggesting that
      oxidative stress also contributes to apoptosis. Although preliminary, this study
      indicates that longitudinal DOSI tissue temperature monitoring provides
      information that can improve our understanding of the mechanisms of tissue
      response during NAC.

PMID- 22408652
TI  - Fibrodysplasia ossificans progressiva: a human genetic disorder of extraskeletal
      bone formation, or--how does one tissue become another?
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare human genetic disease in
      which de novo osteogenesis-a developmental process occurring during embryonic
      skeletal formation-is induced aberrantly and progressively beginning during early
      childhood in soft connective tissues. Episodic initiation of spontaneous bone
      forming lesions occurs over time, affecting a generally predictable sequence of
      body locations following a pattern similar to that of the developing embryonic
      skeleton. The heterotopic (extraskeletal) bone formation in FOP can also be
      induced by connective tissue injury. At the tissue level, an initial tissue
      degradation phase is followed by a tissue formation phase during which soft
      connective tissues are replaced by bone tissue through endochondral osteogenesis.
      This extraskeletal bone is physiologically normal and develops through the same
      series of tissue differentiation events that occur during normal embryonic
      skeletal development. The underlying genetic mutation in FOP alters the signals
      that regulate induction of cell differentiation leading to bone formation. In
      addition to postnatal heterotopic ossification, FOP patients show specific
      malformations of skeletal elements indicating effects on bone formation during
      embryonic development as well. Nearly all cases of FOP are caused by the
      identical mutation in the ACVR1 gene that causes a single amino acid
      substitution, R206H, in the bone morphogenetic protein (BMP) type I receptor
      ACVR1 (formerly known as ALK2). This mutation causes mild constitutive activation
      of the BMP signaling pathway and identifies ACVR1 as a key regulator of cell fate
      decisions and bone formation, providing opportunities to investigate previously
      unrecognized functions for this receptor during tissue development and
      homeostasis.

PMID- 22408651
TI  - Neuroinflammatory Cytokines-The Common Thread in Alzheimer's Pathogenesis.
AB  - This article discusses the potential role of the cytokine cycle and its corollary
      as drivers of the relentless progression of Alzheimer's neuropathologies, whether
      they are the result of gene mutations, gene polymorphisms, and/or environmental
      and comorbid conditions. Based on the discovery of cytokine overexpression as an
      accompaniment to the dementia-related glial activation, the cytokine hypothesis
      was proposed. This states that in response to the negative impact on neurons of
      known and unknown risk factors-which include genetic inheritance, comorbid and
      environmental factors-microglia and astrocytes become activated and produce
      excess amounts of the immune-modulating cytokine interleukin-1 (IL-1) and the
      neuritogenic cytokine S100B, respectively. Finding that these glial events occur
      in fetuses and neonates with Down syndrome provided the first evidence that
      productive immune responses by activated glia precede rather than follow overt AD
      related pathology. This finding can be added to the demonstration of IL-1
      induction of amyloid beta (Abeta) precursor protein and astrocyte activation with
      excess production of neuritogenic factor S100B. This combination suggests that IL
      1 and S100B overexpression would favor the Abeta production and dystrophic
      neurite growth necessary for laying down neuritic Abeta plaques. This, together
      with demonstration of IL-1 induction of excessive production of the precursors of
      other features common in AD prompted a corollary to the cytokine hypothesis. The
      corollary states that regardless of the primary cause of the neuronal insult, the
      result will be chronic glial activation, which in turn will result in further
      neuronal injury, still more glial activation with excess cytokine expression and
      so on. This article discusses known causes, genetic and environmental risk
      factors, and comorbid conditions, and the potential contribution of glial
      activation with excessive cytokine expression to each.

PMID- 22408654
TI  - Prevalence of neurological disorders in children less than 10 years of age in RS
      Pura town of Jammu and Kashmir.
AB  - OBJECTIVE: To determine the prevalence of major neurological disorders in
      children less than 10 years of age. MATERIALS AND METHODS: The study was
      conducted in the framework of a population based, single centre, cross-sectional
      study at Ranbir Singh Pura town, 22 km south-west of Jammu city. RESULTS: Eight
      cases of active epilepsy with a crude prevalence rate of 202 (95% confidence
      interval [CI] 180-220), five cases of Febrile seizures with a crude prevalence of
      126 (95% CI 110-140) and eleven cases of cerebral palsy with a crude prevalence
      rate of 277 (95% CI 245-309) per 100,000 were found. Very few cases of other
      major neurological disorders were found. The prevalence rate of these disorders
      is estimated at same level as for other disorders such as - Post-meningitic
      sequelae, Infantile hemiparesis, Spinal deformity and Tic disorder is at 25 (95%
      CI 15-34) per 100,000. INTERPRETATION: On the basis of the data obtained, the
      present study provides some valuable data on common neurological diseases among
      children in RS Pura town of Jammu district of Jammu and Kashmir.

PMID- 22408655
TI  - Prevalence of migraine and tension-type headache among school children in Yazd,
      Iran.
AB  - OBJECTIVE: The etiology and pathogenesis of migraine and other types of headache
      are still under discussion. The aim of this study was to investigate the
      prevalence of migraine and tension-type headache and its association with
      demographic variables among schoolchildren. MATERIALS AND METHODS: A cross
      sectional study was performed on 930 school children (aged 12-14 years) through
      cluster sampling method. International Headache Society criteria were used for
      diagnosis. Descriptive statistics and logistic regression were used for data
      analysis. RESULTS: The prevalence of migraine headache was 12.3% (95% CI: 10.2
      14.4) and tension-type headache was 4.2% (95% CI: 2.9-5.6). The factor associated
      with migraine in multivariate analysis were age and sleep disturbances.
      CONCLUSIONS: Migraine is common among school children, although it may be under
      recognized. Because children with migraine and tension-type headache have a high
      prevalence of sleep disturbances, they should always be evaluated for the
      presence of sleep problems.

PMID- 22408656
TI  - Neuroradiological findings in GM2 gangliosidosis variant B1.
AB  - GM2 gangliosidosis variant B1 is a very rare lysosomal disorder. As per our
      knowledge, to date, only one article depicting the magnetic resonance imaging
      (MRI) findings of GM2 gangliosidosis variant B1 is available in the literature.
      We are the first to describe the neuroradiological findings in an Indian patient
      diagnosed with GM2 gangliosidosis variant B1.

PMID- 22408657
TI  - Sturge-Weber syndrome with bilateral facial nevus and early cerebral
      calcification.
AB  - Sturge Weber syndrome is characterized by unilateral facial nevus with a tram
      track appearance on CT scan. However different variants have been described. We
      report one such variant in a 14 months old child with bilateral facial nevus and
      bilateral curvilinear calcification. There was also global development delay and
      early onset of seizures reflecting the severe bilateral cortical changes.

PMID- 22408658
TI  - Large occipito-cervical encephalocele with Chiari III malformation.
AB  - Chiari type III is the rarest of the Chiari malformations and is usually
      associated with high morbidity and mortality. Treatment consists of primary
      closure of the encephalocele with or without cerebro-spinal fluid (CSF) shunting.
      In our case, the patient was treated with ventriculoperitoneal shunt followed by
      excision of the encephalocele. We propose that large encephaloceles should be
      treated with CSF shunting prior to repair of the sac so as to achieve optimal
      result.

PMID- 22408659
TI  - Transalar transphenoidal meningoencephalocele: A rare cause of respiratory
      distress in a neonate.
AB  - Respiratory distress in an infant is a common cause of admission in neonatal
      intensive care facility. Obstructive lesions of the airway constitute a minority
      of problems in the new born but present a diagnostic challenge. We present a 30
      day-old male infant admitted with respiratory distress who was diagnosed to have
      an oropharyngeal cystic mass which on further evaluation by computed tomography
      and magnetic resonance imaging revealed a transalar transsphenoidal
      meningoencephalocele herniating into the oral cavity through a congenital split
      palate. The patient was operated successfully using a transpalatal approach
      leading to complete resolution of respiratory distress.

PMID- 22408660
TI  - Iniencephaly clausus: A case report with review of literature.
AB  - Iniencephaly is a rare neural tube defect characterized by extreme retroflexion
      of the head with the absence of neck due to spinal deformities. The important
      features that help us to diagnose a case of iniencephaly are occipital bone
      deficit leading to enlarged foramen magnum, fusion of malformed cervical and
      thoracic vertebrae, and upward turned face with chin continuous with chest
      because of the absence of neck. The differential diagnoses include anencephaly
      with spinal retroflexion, Klippel-Fiel syndrome, nuchal tumors such as teratoma,
      goiter, and lymphangioma and Jarcho-Levin syndrome. Previously many case reports
      on radiological features of iniencephaly are published, but there are very few
      articles on necropsy findings and differential diagnosis. In the present case we
      have discussed in detail the necropsy findings of iniencephaly clausus with
      special reference to differential diagnosis.

PMID- 22408661
TI  - Bulbar dysfunction: An early presentation of congenital myasthenic syndrome in
      three infants.
AB  - Congenital myasthenic syndromes are a group of rare genetic disorders affecting
      neuromuscular transmission. A high index of suspicion is required as clinical
      manifestations can be variable and nonspecific. Clinical phenotype includes
      arthrogryposis, respiratory crises, facial deformities, and weakness. With the
      availability of molecular genetics, this group of conditions can now be more
      clearly delineated and targeted treatment can be initiated. We describe three
      children who presented with bulbar difficulties and had Cholinergic receptor,
      nicotinic, and epsilon or receptor associated protein of the synapse mutations.

PMID- 22408662
TI  - Ictal syncope: A neurologist's perspective.
AB  - Isolated syncope is a rare manifestation of seizures in children and it is a
      poorly localizing sign in the evaluation of seizures in children. Many times,
      such episodes are mistaken as primary cardiac dysrhythmias and we present
      herewith one such case in a child, who succumbed to the illness despite
      treatment.

PMID- 22408663
TI  - Obstructive hydrocephalus resulting from cerebral venous thrombosis.
AB  - Cerebral venous thrombosis is a rare form of stroke in childhood. Increased
      intracranial pressure is a well-defined complication of cerebral venous
      thrombosis but obstructive hydrocephalus as a presentation finding of cerebral
      venous thrombosis is rarely described. A child case of cerebral sinus thrombosis
      presenting with obstructive hydrocephalus and management of clinical condition is
      presented with discussion of reported cases and treatment recommendations.

PMID- 22408664
TI  - Spontaneous spinal extradural hematoma in a child with hemophilia B, surgery or
      medical management - A dilemma?
AB  - Spontaneous spinal extradural hematoma is a rare clinical scenario which may be
      secondary to a variety of etiologies. Spinal epidural hematoma is an extremely
      rare complication in hemophiliacs. It usually runs an acute course often leading
      to rapid onset of neurological deficits. MR imaging is the diagnostic modality of
      choice and early, prompt treatment will often yield fruitful results. We report a
      case of spontaneous spinal EDH in a 5-year-old male child with Hemophilia B, who
      was managed conservatively and was doing well at last follow-up, 2 years after
      treatment. The authors discuss the role of factor replacement therapy vis-a-vis
      surgery in such a scenario.

PMID- 22408665
TI  - Epistaxis as first clinical presentation in a child with giant prolactinoma: Case
      report and review of literature.
AB  - Pituitary tumour have a wide way of presentation. Epistaxis due to pituitary
      adenoma has been rarely reported. There is no report of bleeding from nose as
      clinical first presentation in a child. We report the first case in literature
      where a child had epistaxis for eight months before deterioration of vision. He
      was found to be having a invasive prolactinoma with normal prolactin levels.

PMID- 22408666
TI  - Reversible posterior encephalopathy syndrome due to intravenous immunoglobulin in
      a child with Guillain-Barre syndrome.
AB  - Reversible posterior leukoencephalopathy syndrome is characterized clinically by
      headache, abnormalities of mental status, and visual perception and seizures. We
      report a rare case of acute encephalopathy following intravenous immunoglobulin
      treatment for Guillain-Barre syndrome in whom posterior reversible encephalopathy
      syndrome developed without severe hypertension.

PMID- 22408667
TI  - Jarcho-Levin syndrome with diastematomyelia: A case report and review of
      literature.
AB  - Jarcho-Levin syndrome (JLS) is a type of segmental costovertebral malformation.
      It is a congenital disorder characterized by a variety of vertebral and costal
      anomalies. Only four cases of Jarcho-Levin syndrome with diastematomyelia have
      been reported in the literature. We report the fifth case of Jarcho-Levin
      syndrome with diastematomyelia and review the literature. A one-and-half-year-old
      male child born of full-term normal delivery was brought with complaints of
      progressively increasing weakness in lower limbs with inability to stand since 1
      month. Radiological examination revealed irregular fusion of ribs, spina bifida,
      and diastematomyelia at L2-L3 vertebral level. The patient underwent L1 to L3
      laminectomy. A large bony spur was identified and excised with microrongeurs.
      Spondylocostal dysplasia may be associated with diastematomyelia or other
      surgically correctable occult intraspinal anomalies which may be diagnosed in
      early asymptomatic stage by magnetic resonance image screening of spine.

PMID- 22408668
TI  - Guillain-Barre syndrome with hyperreflexia: A variant.
AB  - Guillain-Barre syndrome (GBS) is a common cause of acute peripheral neuropathy
      and is characterized by hyporeflexia or areflexia. Hyperreflexia has been rarely
      reported with acute motor axonal neuropathy. A 10-year-old boy presented with
      asymmetrical weakness of upper and lower limbs and change of voice. Weakness
      progressed in the hospital with involvement of multiple cranial nerves, preserved
      deep tendon jerks with extensor plantar, and normal abdominal reflexes. He was
      treated with IV immunoglobulin and IV methylprednisolone. He was able to walk
      with support with normal voice at the time of discharge. GBS should be a
      differential diagnosis in patients with acute quadriparesis even if there are
      preserved deep tendon reflexes.

PMID- 22408669
TI  - Striatal necrosis in type 1 glutaric aciduria: Different stages in two siblings.
AB  - Two siblings born of a consanguineous marriage with history of neurologic
      deterioration were imaged. Imaging features are classical of glutaric aciduria
      type 1 (GA-1), acute (striatal necrosis) stage in younger sibling, and chronic
      stage in older sibling. GA-1 is an autosomal recessive disease with typical
      imaging features. Greater awareness about this condition among clinicians and
      radiologists is essential for early diagnosis and prevention of its catastrophic
      consequences. Striatal necrosis with stroke-like signal intensity on imaging
      correlates with clinical stage of patients.

PMID- 22408670
TI  - Transoral extrusion of the ventriculo-peritoneal shunt: A case report and review
      of literature.
AB  - There are several case reports of complications of ventriculo-peritoneal shunt.
      Extrusion of the peritoneal end of the shunt through mouth is extremely rare.
      There are few case reports. We are reporting one such case. A 1-year male child
      was admitted with the peritoneal end of ventriculo-peritoneal shunt coming out
      through mouth since 6 hours after an episode of vomiting. He was conscious and
      had no neurological deficits. The anterior fontanelle was depressed. There was no
      infection. The peritoneal end of the shunt was removed through the mouth. Shunt
      revision was performed. The patient was discharged 10 days after the revision
      without any complications. At 1-year follow-up the patient is doing well.
      Possible mechanisms of bowel perforation are discussed. Pulling the peritoneal
      end through mouth is probably the best way of management as small spontaneous gut
      perforation seals off spontaneously. It also decreases the possibility of
      infection, other morbidities, and hospital stay.

PMID- 22408671
TI  - Preoperative diffuse leptomeningeal spread in a medulloblastoma: Paraplegia
      following surgery for posterior fossa and call for newer management protocols.
AB  - Management of patients with medulloblastoma presenting with multiple metastasis
      in subarachnoid space preoperatively is unclear. An 11-year-old boy presented
      with vermian medulloblastoma with an unusually long segment cervico-dorsal lesion
      and suprasellar lesion. The child underwent a posterior fossa craniotomy (prone
      position) and excision of vermian mass. He developed paraplegia in the immediate
      postoperative period, the possible causes for which are being discussed. Besides,
      treatment options for patients presenting with disseminated disease
      preoperatively have been highlighted. Preoperative chemotherapy to downstage such
      lesions may be tried and such complications could be avoided.

PMID- 22408672
TI  - An interesting case of interparietal encephalocele.

PMID- 22408673
TI  - Dura-based cavernous hemangioma presenting as large intracerebral hematoma in a
      child: A rare clinico-pathological entity.

PMID- 22408674
TI  - Extradural hematoma in an infant of 8 months.

PMID- 22408675
TI  - Aseptic meningitis following intravenous immunoglobulin therapy of common
      variable immunodeficiency.

PMID- 22408676
TI  - Histiocytosis-related cerebellar leukoencephalopathy.

PMID- 22408677
TI  - Magnesium for neuroprotection.

PMID- 22408678
TI  - Response.

PMID- 22408679
TI  - Accidental self-strangulation in a child.

PMID- 22408680
TI  - Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy and PEHO
      like syndrome: Report of two cases.

PMID- 22408681
TI  - Cervical and intracranial MRI findings in tetralogy of Fallot: Association with a
      persistent hypoglossal artery.

PMID- 22408682
TI  - Catastrophic brain metastatic lesions in a child with cutaneous melanoma.

PMID- 22408683
TI  - Over-expression of HER-2 is associated with the stage in carcinomas of the
      urinary bladder.
AB  - BACKGROUND: The frequency of over-expression of human epidermal growth factor
      receptor-2 (HER-2) in bladder cancer is one of the highest among all human
      malignancies. This over-expression is thought to play a role in aberrant
      proliferation of cancer cells. Studies on HER-2 expression in bladder carcinoma
      have shown heterogeneous results. PURPOSE: The aim of the study was to evaluate
      the status of HER-2 protein expression in patients with invasive carcinomas of
      the urinary bladder as related to tumor grade and stage. MATERIALS AND METHODS:
      Archival samples from 39 patients (6 women, 33 males) with urinary bladder cancer
      were analyzed for HER-2 over-expression, using immunohistochemistry with the
      HercepTest. RESULTS: HER-2 over-expression was observed in 23/39 tumors (59%) and
      was more frequent in high-grade than in low-grade carcinomas, but the difference
      was not statistically significant. A significant correlation was established
      between HER-2 over-expression and tumor stage (p=0.011). HER-2 expression was
      more frequent in transitional cell carcinomas (TCC) and adenocarcinomas (AC) as
      compared with squamous cell carcinoma (SCC). Patients' age and sex were not
      related to HER-2 over-expression. CONCLUSION: Over-expression of HER-2 was
      frequent in carcinomas of the urinary bladder. Knowing the HER-2 status would be
      helpful in formulating a rational treatment strategy for patients with urinary
      bladder cancer.

PMID- 22408684
TI  - Infectious diseases are analogous with cancer. Hypothesis and implications.
AB  - We propose to disclose first degree analogous features between cancer and
      infectious diseases and to find out whether these similarities are superficial
      and negligible, due to the use of the same bodily pathways by the two categories
      of disease or if they represent significantly parallel characteristics. We have
      found several primary analogous features, predominantly regarding pathways of
      spread, but to some extent also concerning the interaction with the immune
      system. Some of the implications to our hypothesis are probably available in the
      recent literature, at the experimental or clinical levels. For example
      endostatin, an angiogenic inhibitor has been used to prevent promotion of
      metastasis in cancer and to reduce granulomas formation in schistosomiasis. An
      ECFR antagonist employed to restrain bronchial vessels proliferation in
      pseudomonas infection, has also been used for the treatment of lung cancer.

PMID- 22408685
TI  - Prostate cancers detected during 5alpha-reductase inhibitor use are smaller, de
      differentiated, but confined when compared to controls.
AB  - RATIONALE: To compare cancers detected during use of 5alpha-reductase inhibitors
      (5alphaRI) with cancers detected in untreated controls stratified for tumor size.
      METHODS: Prostate biopsies were performed on 235 consecutive patients "for cause"
      (elevated or rising PSA, positive digital rectal examination, or focal hypoechoic
      lesion). Fifty patients were excluded for a prior diagnosis of cancer, leaving
      185 as the study group (5alphaRI=41, control=144). Patients in the 5alphaRI group
      had been treated for a mean of 3.5 years. Cancer was ultimately diagnosed in
      114/185 patients. RESULTS: Cancer was diagnosed in 31/41 (76%) of patients
      treated with 5alphaRI and 83/144 (58%) of the control group (p=0.04). Control
      tumors were larger (14.3 mm) than those in 5alphaRI treated patients (9.4 mm,
      p=0.0007). No differences in mean PSA or PSA kinetics were detected between
      groups. For tumors less than 1.0 cm, the proportion of high grade cancers
      (Gleason 7-10 and Gleason 4+3-10) was higher in 5alphaRI subjects than in
      controls (p<0.05). Fewer 5alphaRI patients had proven extracapsular extension
      than controls, but this difference did not reach statistical significance
      (p=0.13). Normal DNA ploidy was more likely to be diagnosed in the 5alphaRI group
      versus controls, but this difference was not statistically significant (81% vs.
      65%, p=0.14). CONCLUSIONS: Cancers diagnosed in patients presenting "for cause"
      treated with 5alphaRI drugs are more likely to be de-differentiated compared to
      controls. However, these tumors are also smaller and less likely to have
      extracapsular extension and abnormal DNA ploidy than controls.

PMID- 22408686
TI  - Does the Loss of ARID1A (BAF-250a) Expression in Endometrial Clear Cell
      Carcinomas Have Any Clinicopathologic Significance? A Pilot Assessment.
AB  - SWI/SNF chromatin-modification complexes use the energy of ATP hydrolysis to
      remodel nucleosomes and to affect transcription and several cellular processes.
      Accordingly, their loss of function has been associated with malignant
      transformation. ARID1A (the expression of whose product, BAF250a, a key complex
      component, is lost when mutated) has recently been identified as a tumor
      suppressor gene that is mutated in 46-57% of ovarian clear cell carcinoma (CCC).
      The purposes of this study are to assess the frequency of loss of BAF250a
      expression in endometrial CCC and whether this loss has any discernable
      clinicopathologic implications. 34 endometrial carcinomas with a CCC component
      (including 22 pure CCC, 8 mixed carcinomas with a 10% CCC component, and 4
      carcinosarcomas with a CCC epithelial component), were evaluated by
      immunohistochemistry using a monoclonal antibody directed against the human
      BAF250a protein. 5 (22.7%) of the 22 pure CCC were entirely BAF250a negative,
      whereas the remainder showed diffuse immunoreactivity. None of 4 carcinosarcomas
      and only 1 (12.5%) of the 8 mixed carcinomas were BAF250a negative. There was no
      discernable relationship between BAF250a immunoreactivity status and tumor
      architectural patterns (solid, papillary or tubulocystic areas) or cell type
      (flat, hobnail or polygonal). Of the 22 patients with pure CCC, 14, 2, 3, and 3
      were International Federation of Gynecology and Obstetrics stages 1, II, III and
      IV respectively. Interestingly, all 5 BAF250a negative cases were late stage
      [stages III or IV] as compared with 1 of 17 BAF250a positive cases (p=0.0002).
      Thus, 83% (5/6) of all late stage cases were BAF250a [-], as compared with 0 (0%)
      of the 16 early stage (I or II) cases (p=.0002). BAF250a negative and positive
      cases did not show any statistically significant difference regarding patient age
      and frequency of lymphovascular invasion or myometrial invasion. As may be
      anticipated from the concentration of late stage cases in the BAF250a negative
      group, patient outcomes were worsened in that group on univariate analysis. In
      conclusion, we found in this pilot assessment that 22.7% of endometrial CCC
      displays complete loss of BAF250a expression. There was a disproportionate
      concentration of BAF250a negative cases in the late stage group, with the
      attendant possibility of an associated worsened prognosis for those CCC patients
      whose tumors are BAF250a negative. These preliminary findings suggest the need
      for larger analyses to evaluate the prognostic significance, if any, of the loss
      of BAF250a expression in this rare histotype of endometrial cancer.

PMID- 22408687
TI  - Robot-assisted laparoscopic prostatectomy in a 68-year-old patient with previous
      heart transplantation and pelvic irradiation.
AB  - We report the case of a 68-year-old man who had previously undergone heart
      transplantation and pelvic irradiation for Hodgkin's lymphoma and who was under
      active surveillance for prostate cancer. In response to his increased prostate
      specific antigen levels and elevated Gleason score, he was offered robot-assisted
      laparoscopic prostatectomy. 

PMID- 22408688
TI  - Effect of computational methodology on the conformational dynamics of the protein
      photosensor LOV1 from Chlamydomonas reinhardtii.
AB  - LOV domains are the light-sensitive protein domains of plant phototropins and
      bacteria. They photochemically form a covalent bond between a flavin
      mononucleotide (FMN) chromophore and a cysteine, attached to the apo-protein,
      upon irradiation with blue light, which triggers a signal in the adjacent kinase.
      Although their signaling state has been well characterized through experimental
      means, their signal transduction pathway as well as dark-state activity are
      generally only poorly understood. Here we show results from molecular dynamics
      simulations where we investigated the effect of thermostating and long-range
      electrostatics on the solution structure and dynamical behavior of the wild-type
      LOV1 domain from the green algae Chlamydomonas reinhardtii in the dark. We
      demonstrate that these computational issues can dramatically affect the
      conformational fluctuations of such protein domains by suppressing configurations
      far from equilibrium or destabilizing local configurations, leading to artificial
      changes of the protein secondary structure as well as the H-bond network formed
      by the amino acids and the FMN. By comparing our calculation results with recent
      experimental data, we show that the non-invasive thermostating strategy, where
      the protein solute is only indirectly coupled to the thermostat via the solvent,
      in conjunction with the particle-mesh Ewald technique, provides dark-state
      conformers, which are in consistency with experimental observations. Moreover,
      our calculations indicate that the LOV1 domains can alter the intersystem
      crossing rate and rate of adduct formation by adjusting the population
      distribution of these dark-state conformers. This might permit them to function
      as a modulator of the signal intensity under low light conditions. ELECTRONIC
      SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12154
      011-0060-z) contains supplementary material, which is available to authorized
      users.

PMID- 22408689
TI  - Critical review of norovirus surrogates in food safety research: rationale for
      considering volunteer studies.
AB  - The inability to propagate human norovirus (NoV) or to clearly differentiate
      infectious from noninfectious virus particles has led to the use of surrogate
      viruses, like feline calicivirus (FCV) and murine norovirus-1 (MNV), which are
      propagatable in cell culture. The use of surrogates is predicated on the
      assumption that they generally mimic the viruses they represent; however, studies
      are proving this concept invalid. In direct comparisons between FCV and MNV,
      their susceptibility to temperatures, environmental and food processing
      conditions, and disinfectants are dramatically different. Differences have also
      been noted between the inactivation of NoV and its surrogates, thus questioning
      the validity of surrogates. Considerable research funding is provided globally
      each year to conduct surrogate studies on NoVs; however, there is little
      demonstrated benefit derived from these studies in regard to the development of
      virus inactivation techniques or food processing strategies. Human challenge
      studies are needed to determine which processing techniques are effective in
      reducing NoVs in foods. A major obstacle to clinical trials on NoVs is the
      perception that such trials are too costly and risky, but in reality, there is
      far more cost and risk in allowing millions of unsuspecting consumers to contract
      NoV illness each year, when practical interventions are only a few volunteer
      studies away. A number of clinical trials have been conducted, providing
      important insights into NoV inactivation. A shift in research priorities from
      surrogate research to volunteer studies is essential if we are to identify
      realistic, practical, and scientifically valid processing approaches to improve
      food safety.

PMID- 22408690
TI  - Respiratory motor control disrupted by spinal cord injury: mechanisms,
      evaluation, and restoration.
AB  - Pulmonary complications associated with persistent respiratory muscle weakness,
      paralysis, and spasticity are among the most important problems faced by patients
      with spinal cord injury when lack of muscle strength and disorganization of
      reciprocal respiratory muscle control lead to breathing insufficiency. This
      review describes the mechanisms of the respiratory motor control and its change
      in individuals with spinal cord injury, methods by which respiratory function is
      measured, and rehabilitative treatment used to restore respiratory function in
      those who have experienced such injury. 

PMID- 22408691
TI  - Defining an Acidosis-Based Ischemic Penumbra from pH-Weighted MRI.
AB  - It has been proposed that the spatial mismatch between deficits on perfusion
      weighted imaging (PWI) and diffusion-weighted imaging (DWI) in MRI can be used to
      decide regarding thrombolytic treatment in acute stroke. However, uncertainty
      remains about the meaning and reversibility of the perfusion deficit and even
      part of the diffusion deficit. Thus, there remains a need for continued
      development of imaging technology that can better define a potentially
      salvageable ischemic area at risk of infarction. Amide proton transfer (APT)
      imaging is a novel MRI method that can map tissue pH changes, thus providing the
      potential to separate the PWI/DWI mismatch into an acidosis-based penumbra and a
      zone of benign oligemia. In this totally noninvasive method, the pH dependence of
      the chemical exchange between amide protons in endogenous proteins and peptides
      and water protons is exploited. Early results in animal models of ischemia show
      promise to derive an acidosis penumbra. Possible translation to the clinic and
      hurdles standing in the way of achieving this are discussed. 

PMID- 22408693
TI  - Superior Neuroprotective Efficacy of LAU-0901, a Novel Platelet-Activating Factor
      Antagonist, in Experimental Stroke.
AB  - Platelet-activating factor (PAF) accumulates during cerebral ischemia, and
      inhibition of this process plays a critical role in neuronal survival. Recently,
      we demonstrated that LAU-0901, a novel PAF receptor antagonist, is
      neuroprotective in experimental stroke. We used magnetic resonance imaging in
      conjunction with behavior and immunohistopathology to expand our understanding of
      this novel therapeutic approach. Sprague-Dawley rats received 2 h middle cerebral
      artery occlusion (MCAo) and were treated with LAU-0901 (60 mg/kg) or vehicle 2 h
      from MCAo onset. Behavioral function, T2-weighted imaging (T2WI), and apparent
      diffusion coefficients were performed on days 1, 3, and 7 after MCAo. Infarct
      volume and number of GFAP, ED-1, and NeuN-positive cells were conducted on day 7.
      Behavioral deficit was significantly improved by LAU-0901 treatment compared to
      vehicle on days 1, 3, and 7. Total lesion volumes computed from T2WI were
      significantly reduced by LAU-0901 on days 1, 3, and 7 (by 83%, 90%, and 96%,
      respectively), which was consistent with decreased edema formation.
      Histopathology revealed that LAU-0901 treatment resulted in significant reduction
      of cortical and subcortical infarct volumes, attenuated microglial infiltration,
      and promoted astrocytic and neuronal survival. These findings suggest LAU-0901 is
      a promising neuroprotectant and provide the basis for future therapeutics in
      patients suffering ischemic stroke. 

PMID- 22408692
TI  - Functional MRI and diffusion tensor imaging of brain reorganization after
      experimental stroke.
AB  - The potential of the adult brain to reorganize after ischemic injury is critical
      for functional recovery and provides a significant target for therapeutic
      strategies to promote brain repair. Despite the accumulating evidence of brain
      plasticity, the interaction and significance of morphological and physiological
      modifications in post-stroke brain tissue remain mostly unclear. Neuroimaging
      techniques such as functional MRI (fMRI) and diffusion tensor imaging (DTI)
      enable in vivo assessment of the spatial and temporal pattern of functional and
      structural changes inside and outside ischemic lesion areas. This can contribute
      to the elucidation of critical aspects in post-stroke brain remodeling.
      Task/stimulus-related fMRI, resting-state fMRI, or pharmacological MRI enables
      direct or indirect measurement of neuronal activation, functional connectivity,
      or neurotransmitter system responses, respectively. DTI allows estimation of the
      structural integrity and connectivity of white matter tracts. Together, these MRI
      methods provide an unprecedented means to (a) measure longitudinal changes in
      tissue structure and function close by and remote from ischemic lesion areas, (b)
      evaluate the organizational profile of neural networks after stroke, and (c)
      identify degenerative and restorative processes that affect post-stroke
      functional outcome. Besides, the availability of MRI in clinical institutions as
      well as research laboratories provides an optimal basis for translational
      research on stroke recovery. This review gives an overview of the current status
      and perspectives of fMRI and DTI applications to study brain reorganization in
      experimental stroke models. 

PMID- 22408694
TI  - Urban air pollution: a representative survey of PM(2.5) mass concentrations in
      six Brazilian cities.
AB  - In urban areas of Brazil, vehicle emissions are the principal source of fine
      particulate matter (PM(2.5)). The World Health Organization air quality
      guidelines state that the annual mean concentration of PM(2.5) should be below 10
      MUg m(-3). In a collaboration of Brazilian institutions, coordinated by the
      University of Sao Paulo School of Medicine and conducted from June 2007 to August
      2008, PM(2.5) mass was monitored at sites with high traffic volumes in six
      Brazilian state capitals. We employed gravimetry to determine PM(2.5) mass
      concentrations, reflectance to quantify black carbon concentrations, X-ray
      fluorescence to characterize elemental composition, and ion chromatography to
      determine the composition and concentrations of anions and cations. Mean PM(2.5)
      concentrations and proportions of black carbon (BC) in the cities of Sao Paulo,
      Rio de Janeiro, Belo Horizonte, Curitiba, Recife, and Porto Alegre were 28.1 +/-
      13.6 MUg m(-3) (38% BC), 17.2 +/- 11.2 MUg m(-3) (20% BC), 14.7 +/- 7.7 MUg m(-3)
      (31% BC), 14.4 +/- 9.5 MUg m(-3) (30% BC), 7.3 +/- 3.1 MUg m(-3) (26% BC), and
      13.4 +/- 9.9 MUg m(-3) (26% BC), respectively. Sulfur and minerals (Al, Si, Ca,
      and Fe), derived from fuel combustion and soil resuspension, respectively, were
      the principal elements of the PM(2.5) mass. We discuss the long-term health
      effects for each metropolitan region in terms of excess mortality risk, which
      translates to greater health care expenditures. This information could prove
      useful to decision makers at local environmental agencies.

PMID- 22408695
TI  - Vehicle emissions and PM(2.5) mass concentrations in six Brazilian cities.
AB  - In Brazil, the principal source of air pollution is the combustion of fuels
      (ethanol, gasohol, and diesel). In this study, we quantify the contributions that
      vehicle emissions make to the urban fine particulate matter (PM(2.5)) mass in six
      state capitals in Brazil, collecting data for use in a larger project evaluating
      the impact of air pollution on human health. From winter 2007 to winter 2008, we
      collected 24-h PM(2.5) samples, employing gravimetry to determine PM(2.5) mass
      concentrations; reflectance to quantify black carbon concentrations; X-ray
      fluorescence to characterize elemental composition; and ion chromatography to
      determine the composition and concentrations of anions and cations. Mean PM(2.5)
      concentrations in the cities of Sao Paulo, Rio de Janeiro, Belo Horizonte,
      Curitiba, Porto Alegre, and Recife were 28, 17.2, 14.7, 14.4, 13.4, and 7.3
      MUg/m(3), respectively. In Sao Paulo and Rio de Janeiro, black carbon explained
      approximately 30% of the PM(2.5) mass. We used receptor models to identify
      distinct source-related PM(2.5) fractions and correlate those fractions with
      daily mortality rates. Using specific rotation factor analysis, we identified the
      following principal contributing factors: soil and crustal material; vehicle
      emissions and biomass burning (black carbon factor); and fuel oil combustion in
      industries (sulfur factor). In all six cities, vehicle emissions explained at
      least 40% of the PM(2.5) mass. Elemental composition determination with receptor
      modeling proved an adequate strategy to identify air pollution sources and to
      evaluate their short- and long-term effects on human health. Our data could
      inform decisions regarding environmental policies vis-a-vis health care costs.

PMID- 22408696
TI  - Preliminary clinical evaluation of short fiber-reinforced composite resin in
      posterior teeth: 12-months report.
AB  - This preliminary clinical trial evaluated 12 month clinical performance of novel
      filling composite resin system which combines short fiber-reinforced composite
      resin and conventional particulate filler composite resin in high stress bearing
      applications. A total of 37 class I and II restorations (compound and complex
      type) were placed in 6 premolars and 31 molars. The restorations were reviewed
      clinically at 6 months (baseline) and 12 months using modified USPHS codes change
      criteria for marginal adaptation, post-operative sensitivity, pulpal pain and
      secondary caries criteria. Photographs and x-rays were obtained for restorative
      analysis. Results of 12 months evaluation showed 5 restorations having little
      marginal leakage (B score) and 1 patient had minor pulpal symptom and post
      operative sensitivity (B score). No secondary caries or bulk fracture was
      detected. The majority of restorations exhibited A scores of the evaluated
      criteria. After 12 months, restorations combining base of short fiber reinforced
      composite resin as substructure and surface layer of hybrid composite resin
      displayed promising performance in high load bearing areas.

PMID- 22408697
TI  - AFM Specific Identification of Bacterial Cell Fragments on Biofunctional
      Surfaces.
AB  - Biointerfaces with a highly sensitive surface designed for specific interaction
      with biomolecules are essential approaches for providing advanced biochemical and
      biosensor assays. For the first time, we have introduced a simple AFM-based
      recognition system capable of visualizing specific bacterial nanofragments and
      identifying the corresponding bacterial type. For this we developed AFM-adjusted
      procedures for preparing IgG-based surfaces and subsequently exposing them to
      antigens. The AFM images reveal the specific binding of Escherichia coli cell
      fragments to the prepared biofunctional surfaces. Moreover, the binding of
      bacterial cell fragments to the affinity surfaces can be characterized
      quantitatively, indicating a 30-fold to 80-fold increase in the quantity of bound
      antigenic material in the case of a specific antigen-antibody pair. Our results
      demonstrate significant opportunities for developing reliable sensing procedures
      for detecting pathogenic bacteria, and the cell can still be identified after it
      is completely destroyed.

PMID- 22408698
TI  - A County-Level Examination of the Relationship Between HIV and Social
      Determinants of Health: 40 States, 2006-2008.
AB  - BACKGROUND: Social determinants of health (SDH) are the social and physical
      factors that can influence unhealthy or risky behavior. Social determinants of
      health can affect the chances of acquiring an infectious disease - such as HIV -
      through behavioral influences and limited preventative and healthcare access. We
      analyzed the relationship between social determinants of health and HIV diagnosis
      rates to better understand the disparity in rates between different populations
      in the United States. METHODS: Using National HIV Surveillance data and American
      Community Survey data at the county level, we examined the relationships between
      social determinants of health variables (e.g., proportion of whites, income
      inequality) and HIV diagnosis rates (averaged for 2006-2008) among adults and
      adolescents from 40 states with mature name-based HIV surveillance. RESULTS:
      Analysis of data from 1,560 counties showed a significant, positive correlation
      between HIV diagnosis rates and income inequality (Pearson correlation
      coefficient rho = 0.40) and proportion unmarried - ages >15 (rho = 0.52). There
      was a significant, negative correlation between proportion of whites and rates
      (rho = -0.67). Correlations were low between racespecific social determinants of
      health indicators and rates. CONCLUSIONS/IMPLICATIONS: Overall, HIV diagnosis
      rates increased as income inequality and the proportion unmarried increased, and
      rates decreased as proportion of whites increased. The data reflect the higher
      HIV prevalence among non-whites. Although statistical correlations were moderate,
      identifying and understanding these social determinants of health variables can
      help target prevention efforts to aid in reducing HIV diagnosis rates. Future
      analyses need to determine whether the higher proportion of singles reflects
      higher populations of gay and bisexual men.

PMID- 22408699
TI  - Partner Referral by HIV-Infected Persons to Partner Counseling and Referral
      Services (PCRS) - Results from a Demonstration Project.
AB  - OBJECTIVE: The objectives of this article are to determine factors associated
      with refusal and agreement to provide partner information, and evaluate the
      effectiveness of referral approaches in offering PCRS. METHODS: Index clients
      from 5 sites that used 3 different PCRS approaches were interviewed to obtain
      demographic and risk characteristics and choice of partner referral method for
      PCRS. Logistic regression was used to assess factors associated with providing
      partner information. RESULTS: The percentage of index clients who refused to
      provide partner information varied by site (7% to 88%). Controlling for PCRS
      approach, index clients who were older than 25 years, male, or reported having
      male-male sex in the past 12 months were more likely (p <0.01) to refuse to
      provide partner information. Overall, 72% of named partners referred by index
      clients were located and offered PCRS. The proportion of partners who were
      located and offered PCRS differed by referral approach used, ranging from 38%
      using contract referral (index clients agree to notify their partners within a
      certain timeframe, else a disease intervention specialist or health care provider
      will notify them) to 98% using dual referral (index clients notify their partners
      with a disease intervention specialist or provider present). CONCLUSION: Success
      in obtaining partner information varied by the PCRS approach used and
      effectiveness in locating and notifying partners varied by the referral approach
      selected. These results provide valuable insights for enhancing partner services.

PMID- 22408700
TI  - Induced Pluripotent Stem Cells-A New Foundation in Medicine.
AB  - Generation of induced pluripotent stem (iPS) cells using defined factors has been
      considered a ground-breaking step towards establishing patient-specific
      pluripotent stem cells for various applications. The isolation of human embryonic
      stem (ES) cells set the standard that pluripotent stem cells are attainable as
      potentially immortal cells for regeneration of many types of tissues. Different
      approaches have been tested to obtain pluripotent stem cells by circumventing the
      need for embryos. iPS cells appear to be an ideal substitute for ES cells. Since
      the first demonstration of creating iPS cells in 2006, tremendous efforts have
      been made into improving iPS cell generation methods and understanding the
      reprogramming mechanism as well as the nature of iPS cells. To improve iPS cell
      generation, several approaches have been taken: (1) eliminate the viral vector
      integration after delivering the defined factors; (2) select different cell types
      that more effectively give rise to iPS cells; (3) use of chemicals to facilitate
      reprogramming; (4) use of protein factors to reprogram cells. The iPS cells are
      also being rigorously characterized in comparison to ES cells. All these efforts
      are made for the purpose of making iPS cells closer to clinical applications.
      This article will give an overview of the following areas: (1) mechanisms of iPS
      cell derivation; (2) characterization of iPS cells; (3) iPS cells for cell-based
      therapy; and (4) iPS cells for studying disease mechanism. Questions as to what
      aspects of iPS cells require further understanding before they may be put to
      clinical use are also discussed.

PMID- 22408701
TI  - From ERPs to Academics.
AB  - Standardized tests have been used to forecast scholastic success of school-age
      children, and have been related to intelligence, working memory, and inhibition
      using neuropsychological tests. However, ERP correlates of standardized
      achievement have not been reported. Thus, the relationship between academic
      achievement and the P3 component was assessed in a sample of 105 children during
      performance on a Go/NoGo task. The Wide Range Achievement Test - 3(rd) edition
      was administered to assess aptitude in reading, spelling, and arithmetic.
      Regression analyses indicated an independent contribution of P3 amplitude to
      reading and arithmetic achievement beyond the variance accounted for by IQ and
      school grade. No such relationship was observed for spelling. These data suggest
      that the P3, which reflects attentional processes involved in stimulus evaluation
      and inhibitory control may be a biomarker for academic achievement during
      childhood.

PMID- 22408703
TI  - Common origins and host-dependent diversity of plant and  animal viromes.
AB  - Many viruses infecting animals and plants share common cores of homologous genes
      involved in the key processes of viral replication. In contrast, genes that
      mediate virus-host interactions including in many cases capsid protein (CP) genes
      are markedly different. There are three distinct scenarios for the origin of
      related viruses of plants and animals: first, evolution from a common ancestral
      virus predating the divergence of plants and animals; second, horizontal transfer
      of viruses, for example, through insect vectors; third, parallel origin from
      related genetic elements. We present evidence that each of these scenarios
      contributed, to a varying extent, to the evolution of different groups of
      viruses.

PMID- 22408704
TI  - Incidence of vesicobullous and erosive disorders of neonates.
AB  - BACKGROUND: The entity vesicobullous disorders in neonates encompasses a varied
      spectrum of disorders varying from self limiting to potentially life threatening
      infectious diseases. OBJECTIVE: To analyse the incidence of dermatoses in
      neonates, stress the importance of simple noninvasive diagnostic procedures with
      perspective to actual need of active intervention. PATIENTS AND METHODS: Forty
      four neonates with vesicobullous lesions in departments of dermatology and
      pediatrics were evaluated with respect to diagnosis, required treatments and
      follow ups. RESULTS: Out of total 44 neonates, 29 were males and 15 females.
      Iinfectious dermatoses accounted for: 9% - staphylococcal pyoderma, 4,5% - Group
      A Streptococcal impetigo, 4,5% - neonatal tinea faciei, 2,3% - neonatal
      candidiasis, 2,3% - neonatal varicella/chickenpox and 2,3% - scabies. Transient
      skin lesions were: 41% - erythema toxicum neonatorum, 9% - milia crystallina,
      6.8% - neonatal acne, 4,5% - sucking blisters, 2,3% - transient neonatal pustular
      melanosis, 2,3% - epidermolysis bullosa simplex, 2,3% - incontinentia pigmentii,
      2,3% - eosinophilic pustular folliculitis, 2,3% - pemphigus vulgaris and 2,3% -
      neonatal herpes simplex. CONCLUSIONS: Care has to be instituted to identify
      accurately infectious diseases and distinguish them from benign transient
      neonatal dermatoses. Some disorders first manifesting during the neonatal period
      may also represent harbingers of potential problems during adulthood. Finally, it
      is relevant to judge whether the treatment is required or not.

PMID- 22408705
TI  - Smoking, alcohol consumption and denture use in patients with oral mucosal
      lesions.
AB  - BACKGROUND: Epidemiologic researches about oral mucosal lesions have been
      performed in different populations. But, in dermatology outpatients, oral mucosal
      lesions have not been investigated previously. OBJECTIVE: We aimed to determine
      the prevalence of oral mucosal lesions among dermatology outpatients and the
      relationship between OML and smoking, alcohol intake, denture and dental filling
      use and skin diseases. METHODS: Randomly selected 1041 dermatology outpatients
      were examined for dermatological diseases and oral mucosal lesions. All of the
      patients were questioned about smoking, alcohol intake, denture and dental
      filling use. RESULTS: In 235 patients, oral mucosal lesions were recorded. 268
      (25.7%) of the patients had history of smoking, 42 (4%) drinking alcohol and 180
      (17.3%) denture and dental filling. 32 (64%) of the smokers, 54 (30%) of denture
      users and 10 (23.8%) alcohol consumers had at least one OML. Age and smoking were
      found as significant risk factors for oral mucosal lesions. Fissured tongue was
      the most common oral lesion and it was seen significantly higher in patients with
      denture. Smoking was risk factor for coated tongue and linea alba. CONCLUSIONS:
      Oral mucosa should be examined carefully even if the patients do not attend with
      the complaint of oral lesions, especially in elderly patients, smokers and
      denture users.

PMID- 22408706
TI  - Specific Pregnancy Dermatoses in 1430 females from Northern India.
AB  - BACKGROUND: The specific dermatoses of pregnancy represent a heterogenous group
      of ill-defined pruritic skin diseases, unique to pregnancy and post partum
      period. OBJECTIVE: The aim of our study was epidemiological and clinical
      evaluation of various specific dermatoses of pregnancy. METHODS: All patients
      visiting our antenatal clinic were screened for various pruritic skin conditions
      and those with specific pregnancy dermatoses were identified and evaluated.
      RESULTS: Out of 1430 patients screened, nearly 5% (70 cases) patients had
      specific dermatoses of pregnancy. Intra hepatic cholestasis was the commonest
      specific pregnancy dermatoses. CONCLUSION: Specific dermatoses of pregnancy can
      be diagnosed primarily on the basis of clinical features. All of these, except
      intra hepatic cholestasis, do not have any effect on normal course of pregnancy.

PMID- 22408707
TI  - Bullous pemphigoid triggered by swine flu vaccination: case report and review of
      vaccine triggered pemphigoid.
AB  - BACKGROUND: Bullous pemphigoid (BP) is an acquired autoimmune blistering disease
      mainly affecting the elderly. Recent reports have shown an association with pre
      existing neurodegenerative diseases. Triggers including diseases, medications and
      vaccination have been reported although in most patients no clear trigger is
      identified. MAIN OBSERVATIONS: We report a case of atypical bullous pemphigoid
      which was strongly suspected to have been triggered by the swine flu vaccination.
      This is the first reported case of pemphigoid triggered by this vaccine.
      CONCLUSIONS: The use of the swine flu vaccine is likely to increase in the future
      and it is important that clinicians are aware of the potential adverse effect of
      swine flu vaccination induced bullous pemphigoid.

PMID- 22408708
TI  - Miliary osteoma cutis of the face.
AB  - BACKGROUND: Miliary osteoma cutis (OC) of the face is a rare benign extra
      skeletal bone formation. For our knowledge, only 23 cases have been reported in
      the English literature. These lesions may be primary or secondary. They cause
      diagnostic, therapeutic and cosmetic concern especially in women who are usually
      concerned. Our purpose is to present a case which is completely documented with
      the clinical, histological and radiological findings. We also report a possible
      pathogenic theory according to our histologic findings. MAIN OBSERVATION: We
      report a case of a multiple miliary OC of the face in a 45-year-old woman which
      suffered from gravidarum acne. These lesions were treated by focal surgical
      treatment. CONCLUSIONS: Based on our histological findings, an osteoblastic
      metaplasia seems to be a possible pathogenic theory. This metaplasia seems to be
      secondary to a chronic inflammation. Concerning therapeutic procedures, they are
      non consensual and debated and are based on surgical or medical treatment. More
      reports are needed in order to assess the therapeutic management of this disease
      and its inducing factors.

PMID- 22408709
TI  - Trichoscopy update 2011.
AB  - Trichoscopy performed with a handheld dermoscope or a videodermoscope became an
      indispensable tool in differential diagnosis of hair and scalp diseases. Current
      research is focusing on trichoscopy of: 1) non-cicatricial alopecia, 2)
      cicatricial alopecia, 3) hair shaft disorders, and 4) inflammatory scalp
      diseases. This review summarizes current knowledge in these four fields of
      research. In all non-cicatricial alopecias presence of empty follicular openings
      is a common trichoscopy finding. In alopecia areata black dots and micro
      exclamation mark hairs and tapered hairs correlate with disease activity, whereas
      yellow dots and vellus hairs correlate with disease severity. In androgenic
      alopecia trichoscopy shows hair shaft thickness heterogeneity, multiple thin and
      vellus hairs, yellow dots, perifollicular discoloration, and predominance of
      follicular units with only one hair. These features predominate in the frontal
      area. In all forms of cicatricial alopecia, trichoscopy shows milky-red or ivory
      white areas lacking follicular openings. In classic lichen planopilaris
      trichoscopy shows perifollicular inflammation, tubular perifollicular scaling,
      elongated, concentric blood vessels and "classic white dots", which merge to form
      white areas. Frontal fibrosing alopecia shows mild perifollicular scaling.
      Folliculitis decalvans is characterized by tufted hairs, large follicular
      pustules with emerging hair shafts and perifollicular starburst pattern
      hyperplasia. In dissecting cellulitis characteristic findings are "3D" yellow
      dots imposed over dystrophic hairs, large, yellow amorphous areas and pinpoint
      white dots with a whitish halo. Trichoscopy is particularly useful to diagnose
      hair shaft abnormalities in trichorrhexis nodosa, trichorrhexis invaginata,
      monilethrix, pili torti, and pili annulati. The method may be also useful in
      diagnosing inflammatory scalp diseases. In discoid lupus erythematosus
      trichoscopy shows large arborizing vessels and large hyperkeratotic folliculilar
      yellow dots. Trichoscopy of scalp psoriasis shows regularly distributed twisted
      and lacelike blood vessels, whereas in seborroic dermatitis thin arborizing
      vessels may be observed. In tinea capitis trichoscopy shows comma, corkscrew and
      zigzag hairs. Examination tinea capitis may be facilitated by UV-light enhanced
      trichoscopy (UVET). In conclusion, trichoscopy is a non-invasive method which may
      be applied in differential diagnosis of most hair and scalp diseases.

PMID- 22408710
TI  - Photoletter to the editor: Exfoliative cheilitis associated with titanium dental
      implants and mercury amalgam.
AB  - Exfoliative cheilitis is an uncommon chronic inflammatory condition that
      generally affects the vermilion of the lips. Its cause is still largely unknown
      an there is no effective treatment. Here we report of a case of exfoliative
      cheilitis possibly caused by mercury-containing dental amalgam in close proximity
      to dental titanium implant in a 41-year-old woman. By patch-testing, she was
      tested positive to thimerosal, palladium, gold, nickel, and copper. There was a
      strong temporal relation between last titanium dental implant and the onset of
      exfoliative cheilitis. Clinicians should be aware that exfoliative cheilitis
      might be associated with an allergy to intraoral dental metals and that titanium
      dental implant should not be implanted in the vicinity of the mercury-containing
      dental amalgam filling, even in presence of mercury amalgam as rootend filling
      material.

PMID- 22408711
TI  - AUTOMATED ANALYSIS OF QUANTITATIVE IMAGE DATA USING ISOMORPHIC FUNCTIONAL MIXED
      MODELS, WITH APPLICATION TO PROTEOMICS DATA.
AB  - Image data are increasingly encountered and are of growing importance in many
      areas of science. Much of these data are quantitative image data, which are
      characterized by intensities that represent some measurement of interest in the
      scanned images. The data typically consist of multiple images on the same domain
      and the goal of the research is to combine the quantitative information across
      images to make inference about populations or interventions. In this paper, we
      present a unified analysis framework for the analysis of quantitative image data
      using a Bayesian functional mixed model approach. This framework is flexible
      enough to handle complex, irregular images with many local features, and can
      model the simultaneous effects of multiple factors on the image intensities and
      account for the correlation between images induced by the design. We introduce a
      general isomorphic modeling approach to fitting the functional mixed model, of
      which the wavelet-based functional mixed model is one special case. With suitable
      modeling choices, this approach leads to efficient calculations and can result in
      flexible modeling and adaptive smoothing of the salient features in the data. The
      proposed method has the following advantages: it can be run automatically, it
      produces inferential plots indicating which regions of the image are associated
      with each factor, it simultaneously considers the practical and statistical
      significance of findings, and it controls the false discovery rate. Although the
      method we present is general and can be applied to quantitative image data from
      any application, in this paper we focus on image-based proteomic data. We apply
      our method to an animal study investigating the effects of opiate addiction on
      the brain proteome. Our image-based functional mixed model approach finds results
      that are missed with conventional spot-based analysis approaches. In particular,
      we find that the significant regions of the image identified by the proposed
      method frequently correspond to subregions of visible spots that may represent
      post-translational modifications or co-migrating proteins that cannot be visually
      resolved from adjacent, more abundant proteins on the gel image. Thus, it is
      possible that this image-based approach may actually improve the realized
      resolution of the gel, revealing differentially expressed proteins that would not
      have even been detected as spots by modern spot-based analyses.

PMID- 22408712
TI  - Bayesian Joint Modeling of Multiple Gene Networks and Diverse Genomic Data to
      Identify Target Genes of a Transcription Factor.
AB  - We consider integrative modeling of multiple gene networks and diverse genomic
      data, including protein-DNA binding, gene expression and DNA sequence data, to
      accurately identify the regulatory target genes of a transcription factor (TF).
      Rather than treating all the genes equally and independently a priori in existing
      joint modeling approaches, we incorporate the biological prior knowledge that
      neighboring genes on a gene network tend to be (or not to be) regulated together
      by a TF. A key contribution of our work is that, to maximize the use of all
      existing biological knowledge, we allow incorporation of multiple gene networks
      into joint modeling of genomic data by introducing a mixture model based on the
      use of multiple Markov random fields (MRFs). Another important contribution of
      our work is to allow different genomic data to be correlated and to examine the
      validity and effect of the independence assumption as adopted in existing
      methods. Due to a fully Bayesian approach, inference about model parameters can
      be carried out based on MCMC samples. Application to an E. coli data set,
      together with simulation studies, demonstrates the utility and statistical
      efficiency gains with the proposed joint model.

PMID- 22408713
TI  - Nonparametric and Semiparametric Analysis of Current Status Data Subject to
      Outcome Misclassification.
AB  - In this article, we present nonparametric and semiparametric methods to analyze
      current status data subject to outcome misclassification. Our methods use
      nonparametric maximum likelihood estimation (NPMLE) to estimate the distribution
      function of the failure time when sensitivity and specificity are known and may
      vary among subgroups. A nonparametric test is proposed for the two sample
      hypothesis testing. In regression analysis, we apply the Cox proportional hazard
      model and likelihood ratio based confidence intervals for the regression
      coefficients are proposed. Our methods are motivated and demonstrated by data
      collected from an infectious disease study in Seattle, WA.

PMID- 22408714
TI  - Discovery of 1,3-Diaminobenzenes as Selective Inhibitors of Platelet Activation
      at the PAR1 Receptor.
AB  - A high-throughput screen of the NIH-MLSMR compound collection, along with a
      series of secondary assays to identify potential targets of hit compounds,
      previously identified a 1,3-diaminobenzene scaffold that targets protease
      activated receptor 1 (PAR1). We now report additional structure-activity
      relationship (SAR) studies that delineate the requirements for activity at PAR1
      and identify plasma-stable analogues with nanomolar inhibition of PAR1-mediated
      platelet activation. Compound 4 was declared as a probe (ML161) with the NIH
      Molecular Libraries Program. This compound inhibited platelet aggregation induced
      by a PAR1 peptide agonist or by thrombin but not by several other platelet
      agonists. Initial studies suggest that ML161 is an allosteric inhibitor of PAR1.
      These findings may be important for the discovery of antithrombotics with an
      improved safety profile.

PMID- 22408715
TI  - Neoadjuvant chemotherapy for locally advanced gastric cancer: With or without
      radiation.
AB  - The role of perioperative chemotherapy for gastric cancer has been established
      for gastric cancers in their advanced stage. In most parts of the world, even in
      Japan and Korea, local recurrence of gastric cancer following curative resection
      remains a problem. Should radiation be added to chemotherapy to achieve better
      local and regional control? What is the current evidence? What are the concerns
      regarding neoadjuvant chemoradiation in terms of safety, efficacy and survival
      benefit? After a serious review of the literature, the authors conclude that it
      is still too early to get a definitive answer but radiation seems promising. It
      may bring a higher pathological response rate. Rationally, more high level
      clinical trials are needed to confirm the role of radiotherapy in the neoadjuvant
      setting or to ascertain subsets of patients who may benefit from it. It is of
      note that surgeons should pay attention to possible complicated circumstances
      following radiotherapy, maintain proper nutrition status and minimize the
      occurrence of postoperative complications. As few data are available in Japan and
      Korea, interpretation and implementation of neoadjuvant radiation or
      chemoradiation should be done with caution.

PMID- 22408716
TI  - Number of lymph nodes after neoadjuvant therapy for rectal cancer: How many are
      needed?
AB  - Neoadjuvant chemoradiation is the standard treatment for advanced rectal tumor,
      providing better local control of disease and potentially increasing sphincter
      preservation surgery. Neoadjuvant radiation may affect the number of lymph nodes
      harvested after resection or alter their prognostic value. Over the past 10
      years, standards for lymph node harvests in colorectal cancer have been proposed.
      Several studies have recommend examination of at least 12 lymph nodes (LNs) in
      the specimen and this number is now used as a reflection of surgical quality.
      Nevertheless, recent reports have identified significantly decreased LN harvests
      in patients treated with neoadjuvant radiation. And preoperative chemoradiation
      has a significant effect on the number of nodes harvested in rectal specimens and
      this should be considered in staging of the tumor. In the near future, the total
      number of nodes will be less important than specific biologic markers in
      detecting high-risk patients and improving their prognosis with adjuvant therapy
      tailored.

PMID- 22408717
TI  - Long-term results of choledochoduodenostomy in benign biliary obstruction.
AB  - AIM: To determine the long-term results of choledochodudenostomy in patients with
      benign billiary obstruction. METHODS: This prospective study was conducted at
      Sheri Kashmir Institute of Medical Sciences Srinagar Kashmir, India over a period
      of 10 years from January 1997 to December 2007. The total number of patients who
      underwent choledochoduodenostomy during this period was 270. On the basis of
      etiology of biliary tract obstruction, patients were divided into a calculus
      group, an oriental cholangiohepatitis group, a benign biliary stricture group and
      others. Patients were followed for a variable period of 13 mo to 15 years.
      RESULTS: Choledochoduodenostomy (CDD) with duo-denotomy was performend in four
      patients. CDD with removal of T- tube, CDD with left hepatic lobectomy and CDD
      with removal of intra biliary ruptured hydatid was performed in three patients
      each. In the remaining patients only CDD was performed. Immediate post operative
      complications were seen in 63 (23%) patients, while long-term complications were
      seen in 28 (11%) patients, which were statistically significant. Three patients
      died during hospitalization while four patients died in the late post-operative
      period. CONCLUSION: Our conclusion is that CDD is safe and produces good long
      term results when a permanent biliary drainage procedure is required.

PMID- 22408718
TI  - Hybrid natural orifice transluminal endoscopic surgery for ileocecal resection.
AB  - Although laparoscopic colectomy is commonly performed around the world, an
      operative wound formed during the surgery is large but not sufficient enough to
      convert for the majority of open surgery. Thus, a certain sized skin incision is
      required to remove the resected colon. Here we report the case of a pure
      laparoscopic ileocecal resection which involves transanal specimen extraction. We
      present a case characterized by a laterally spreading type of tumor of the cecum.
      We performed a pure laparoscopic ileocecal resection and the resected specimen
      was removed transanally using colonoscopy. Intracorporeal functional anastomosis
      was then performed using a flexible linear stapling device under supporting
      barbed suture traction. The patient was discharged without complications on
      postoperative day 4. Laparoscopic colectomy performed with minimal incision could
      essentially increase the usage of this surgical technique. Although our method is
      restricted to flat or small lesions, we think it is a feasible and realistic
      solution for minimization of operative invasion because it involves specimen
      extraction through a natural orifice.

PMID- 22408719
TI  - The Synthesis and Evaluation of Dihydroquinazolin-4-ones and Quinazolin-4-ones as
      Thyroid Stimulating Hormone Receptor Agonists.
AB  - We herein describe the rapid synthesis of a diverse set of dihydroquinazolin-4
      ones and quinazolin-4-ones, their biological evaluation as thyroid stimulating
      hormone receptor (TSHR) agonists, and SAR analysis. Among the compounds screened,
      8b was 60-fold more potent than the hit compound 1a, which was identified from a
      high throughput screen of over 73,000 compounds.

PMID- 22408720
TI  - A localized meshless approach for modeling spatial-temporal calcium dynamics in
      ventricular myocytes.
AB  - Spatial-temporal calcium dynamics due to calcium release, buffering and re
      uptaking plays a central role in studying excitation-contraction (E-C) coupling
      in both normal and diseased cardiac myocytes. In this paper, we employ a meshless
      method, namely, the local radial basis function collocation method (LRBFCM), to
      model such calcium behaviors by solving a nonlinear system of reaction-diffusion
      partial differential equations. In particular, a simplified structural unit
      containing a single transverse tubule (T-tubule) and its surrounding half
      sarcomeres is investigated using the meshless method. Numerical results are
      compared with those generated by finite element methods, showing the capability
      and efficiency of the LRBFCM in modeling calcium dynamics in ventricular
      myocytes. The single T-tubule model is also extended to the whole-cell scale with
      T-tubules excluded to demonstrate the scalability of the proposed meshless method
      in handling very large domains. The experiments have shown that the LRBFCM is
      suitable to multiscale modeling of calcium dynamics in ventricular myocytes with
      high accuracy and efficiency.

PMID- 22408721
TI  - The zinc-ribbon domain of Helicobacter pylori HP0958: requirement for RpoN
      accumulation and possible roles of homologs in other bacteria.
AB  - BACKGROUND: Helicobacter pylori HP0958 protein (FlgZ) prevents the rapid turnover
      of RpoN (sigma(54)), a transcription factor required for expression of several
      flagellar genes in H. pylori. FlgZ possesses a zinc-ribbon domain (DUF164) that
      contains two conserved CXXC motifs which coordinate a zinc ion and is thought to
      interact with nucleic acids or proteins. Two conserved cysteine residues in FlgZ
      (Cys-202 and Cys-223) were replaced with serine to assess their significance in
      FlgZ function. After confirming the importance of the CXXC motifs in the DUF164
      domain of FlgZ, the distribution of DUF164 proteins and RpoN homologs in other
      bacteria was examined to determine if a correlation existed for the concurrence
      of the two proteins. RESULTS: Levels of RpoN were greatly reduced in H. pylori
      strains that expressed the FlgZ(C202S) or FlgZ(C223S) variants. The FlgZ(C202S)
      variant, but not the FlgZ(C223S) variant, accumulated at levels similar to the
      wild-type protein. DUF164 proteins are not universally distributed and appear to
      be absent in several major bacterial taxa, including Cyanobacteria as well as
      Alpha-, Beta- and Gammaproteobacteria. With the exception of the Actinobacteria,
      members of which generally lack RpoN, genes encoding DUF164 proteins and RpoN are
      frequently found in the same genome. Interestingly, many of the DUF164 proteins
      in Actinobacteria and Bacteroidetes lack most or even all of the conserved
      cysteine residues. CONCLUSIONS: These findings suggest the importance of the zinc
      ribbon domain of FlgZ in protecting RpoN from turnover. Since many bacteria that
      possess a DUF164 protein also contain RpoN, DUF164 proteins may have roles in
      RpoN protection or function in other bacteria.

PMID- 22408722
TI  - Signatures of natural selection among lineages and habitats in Oncorhynchus
      mykiss.
AB  - Recent advances in molecular interrogation techniques now allow unprecedented
      genomic inference about the role of adaptive genetic divergence in wild
      populations. We used high-throughput genotyping to screen a genome-wide panel of
      276 single nucleotide polymorphisms (SNPs) for the economically and culturally
      important salmonid Oncorhynchus mykiss. Samples included 805 individuals from 11
      anadromous and resident populations from the northwestern United States and
      British Columbia, and represented two major lineages including paired populations
      of each life history within single drainages of each lineage. Overall patterns of
      variation affirmed clear distinctions between lineages and in most instances,
      isolation by distance within them. Evidence for divergent selection at eight
      candidate loci included significant landscape correlations, particularly with
      temperature. High diversity of two nonsynonymous mutations within the peptide
      binding region of the major histocompatibility complex (MHC) class II (DAB) gene
      provided signatures of balancing selection. Weak signals for potential selection
      between sympatric resident and anadromous populations were revealed from genome
      scans and allele frequency comparisons. Our results suggest an important adaptive
      role for immune-related functions and present a large genomic resource for future
      studies.

PMID- 22408723
TI  - Intense harvesting of eastern wolves facilitated hybridization with coyotes.
AB  - Despite ethical arguments against lethal control of wildlife populations, culling
      is routinely used for the management of predators, invasive or pest species, and
      infectious diseases. Here, we demonstrate that culling of wildlife can have
      unforeseen impacts that can be detrimental to future conservation efforts.
      Specifically, we analyzed genetic data from eastern wolves (Canis lycaon) sampled
      in Algonquin Provincial Park (APP), Ontario, Canada from 1964 to 2007. Research
      culls in 1964 and 1965 killed the majority of wolves within a study region of
      APP, accounting for approximately 36% of the park's wolf population at a time
      when coyotes were colonizing the region. The culls were followed by a significant
      decrease in an eastern wolf mitochondrial DNA (mtDNA) haplotype (C1) in the
      Park's wolf population, as well as an increase in coyote mitochondrial and
      nuclear DNA. The introgression of nuclear DNA from coyotes, however, appears to
      have been curtailed by legislation that extended wolf protection outside park
      boundaries in 2001, although eastern wolf mtDNA haplotype C1 continued to decline
      and is now rare within the park population. We conclude that the wolf culls
      transformed the genetic composition of this unique eastern wolf population by
      facilitating coyote introgression. These results demonstrate that intense
      localized harvest of a seemingly abundant species can lead to unexpected
      hybridization events that encumber future conservation efforts. Ultimately,
      researchers need to contemplate not only the ethics of research methods, but also
      that future implications may be obscured by gaps in our current scientific
      understanding.

PMID- 22408724
TI  - Humid tropical rain forest has expanded into eucalypt forest and savanna over the
      last 50 years.
AB  - Tropical rain forest expansion and savanna woody vegetation thickening appear to
      be a global trend, but there remains uncertainty about whether there is a common
      set of global drivers. Using geographic information techniques, we analyzed
      aerial photography of five areas in the humid tropics of northeastern Queensland,
      Australia, taken in the 1950s and 2008, to determine if changes in rain forest
      extent match those reported for the Australian monsoon tropics using similar
      techniques. Mapping of the 1950s aerial photography showed that of the combined
      study area (64,430 ha), 63% was classified as eucalypt forests/woodland and 37%
      as rain forest. Our mapping revealed that although most boundaries remained
      stable, there was a net increase of 732 ha of the original rain forest area over
      the study period, and negligible conversion of rain forest to eucalypt
      forest/woodland. Statistical modeling, controlling for spatial autocorrelation,
      indicated distance from preexisting rain forest as the strongest determinant of
      rain forest expansion. Margin extension had a mean rate across the five sites of
      0.6 m per decade. Expansion was greater in tall open forest types but also
      occurred in shorter, more flammable woodland vegetation types. No correlations
      were detected with other local variables (aspect, elevation, geology, topography,
      drainage). Using a geographically weighted mean rate of rain forest margin
      extension across the whole region, we predict that over 25% of tall open forest
      (a forest type of high conservation significance) would still remain after 2000
      years of rain forest expansion. This slow replacement is due to the convoluted
      nature of the rain forest boundary and the irregular shape of the tall open
      forest patches. Our analyses point to the increased concentration of atmospheric
      CO(2) as the most likely global driver of indiscriminate rain forest expansion
      occurring in northeastern Australia, by increasing tree growth and thereby
      overriding the effects of fire disturbance.

PMID- 22408725
TI  - Macroevolutionary patterns of bumblebee body size: detecting the interplay
      between natural and sexual selection.
AB  - Bumblebees and other eusocial bees offer a unique opportunity to analyze the
      evolution of body size differences between sexes. The workers, being sterile
      females, are not subject to selection for reproductive function and thus provide
      a natural control for parsing the effects of selection on reproductive function
      (i.e., sexual and fecundity selection) from other natural selection. Using a
      phylogenetic comparative approach, we explored the allometric relationships among
      queens, males, and workers in 70 species of bumblebees (Bombus sp.). We found
      hyperallometry in thorax width for males relative to workers, indicating greater
      evolutionary divergence of body size in males than in sterile females. This is
      consistent with the hypothesis that selection for reproductive function, most
      probably sexual selection, has caused divergence in male size among species. The
      slope for males on workers was significantly steeper than that for queens on
      workers and the latter did not depart from isometry, providing further evidence
      of greater evolutionary divergence in male size than female size, and no evidence
      that reproductive selection has accelerated divergence of females. We did not
      detect significant hyperallometry when male size was regressed directly on queen
      size and our results thus add the genus Bombus to the increasing list of clades
      that have female-larger sexual size dimorphism and do not conform to Rensch's
      rule when analyzed according to standard methodology. Nevertheless, by using
      worker size as a common control, we were able to demonstrate that bumblee species
      do show the evolutionary pattern underlying Rensch's rule, that being correlated
      evolution of body size in males and females, but with greater evolutionary
      divergence in males.

PMID- 22408726
TI  - Population decrease of Scirpophaga incertulas Walker (Lepidoptera Pyralidae)
      under climate warming.
AB  - Scirpophaga incertulas Walker is an important agricultural pest in Asia. Only few
      studies are available on its long-term population dynamics under climate warming.
      In this study, we used the linear and generalized additive models (GAMs) to
      analyze the historical dataset of >50 years on this pest at Xinfeng County of
      Jiangxi Province, China. The main objective of this study was to explore the
      effects of density (delayed) dependence and minimum annual temperature (MAT),
      which indirectly reflects climate warming, on the population dynamics of this
      pest. We found that both density dependence and MAT have significant influence on
      the annual population growth rate. The GAMs had relatively better applicability
      to the dataset than the linear models. Nonparametric model provided satisfactory
      goodness-of-fit (R(2) > 0.5). At Xinfeng County, the MAT had a significant effect
      on the annual population growth rate of S. incertulas. The annual population
      growth rate of S. incertulas decreased with increase in MAT. Therefore, S.
      incertulas population becomes smaller and smaller in Southern China due to
      climate warming. The current study has two contributions: (1) providing a
      suitable method for predicting the annual population growth rate of S.
      incertulas, and (2) demonstrating that climate warming could decrease the S.
      incertulas population.

PMID- 22408727
TI  - Ericoid mycorrhizal root fungi and their multicopper oxidases from a temperate
      forest shrub.
AB  - Ericoid mycorrhizal fungi (ERM) may specialize in capturing nutrients from their
      host's litter as a strategy for regulating nutrient cycles in terrestrial
      ecosystems. In spite of their potential significance, we know little about the
      structure of ERM fungal communities and the genetic basis of their saprotrophic
      traits (e.g., genes encoding extracellular enzymes). Rhododendron maximum is a
      model ERM understory shrub that influences the nutrient cycles of montane
      hardwood forests in the southern Appalachians (North Carolina, USA). We sampled
      ERM roots of R. maximum from organic and mineral soil horizons and identified
      root fungi by amplifying and sequencing internal transcribed spacer (ITS)
      ribosomal DNA (rDNA) collected from cultures and clones. We observed 71 fungal
      taxa on ERM roots, including known symbionts Rhizoscyphus ericae and Oidiodendron
      maius, putative symbionts from the Helotiales, Chaetothyriales, and Sebacinales,
      ectomycorrhizal symbionts, and saprotrophs. Supporting the idea that ERM fungi
      are adept saprotrophs, richness of root-fungi was greater in organic than in
      mineral soil horizons. To study the genetic diversity of oxidative enzymes that
      contribute to decomposition, we amplified and sequenced a portion of genes
      encoding multicopper oxidases (MCOs) from ERM ascomycetes. Most fungi possessed
      multiple copies of MCO sequences with strong similarities to known ferroxidases
      and laccases. Our findings indicate that R. maximum associates with a
      taxonomically and ecologically diverse fungal community. The study of MCO gene
      diversity and expression may be useful for understanding how ERM root fungi
      regulate the cycling of nutrients between the host plant and the soil
      environment.

PMID- 22408728
TI  - Sexual selection on song and cuticular hydrocarbons in two distinct populations
      of Drosophila montana.
AB  - Sexual selection has the potential to contribute to population divergence and
      speciation. Most studies of sexual selection in Drosophila have concentrated on a
      single signaling modality, usually either courtship song or cuticular
      hydrocarbons (CHCs), which can act as contact pheromones. We have examined the
      relationship between both signal types and reproductive success using F(1-3)
      offspring of wild-collected flies, raised in the lab. We used two populations of
      the Holarctic species Drosophila montana that represent different phylogeographic
      clades that have been separate for ca. 0.5 million years (MY), and differ to some
      extent in both traits. Here, we characterize the nature and identify the targets
      of sexual selection on song, CHCs, and both traits combined within the
      populations. Three measures of courtship outcome were used as fitness proxies.
      They were the probability of mating, mating latency, and the production of
      rejection song by females, and showed patterns of association with different
      traits that included both linear and quadratic selection. Courtship song
      predicted courtship outcome better than CHCs and the signal modalities acted in
      an additive rather than synergistic manner. Selection was generally consistent in
      direction and strength between the two populations and favored males that sang
      more vigorously. Sexual selection differed in the extent, strength, and nature on
      some of the traits between populations. However, the differences in the
      directionality of selection detected were not a good predictor of population
      differences. In addition, a character previously shown to be important for
      species recognition, interpulse interval, was found to be under sexual selection.
      Our results highlight the complexity of understanding the relationship between
      within-population sexual selection and population differences. Sexual selection
      alone cannot predict differences between populations.

PMID- 22408729
TI  - Clock gene variation in Tachycineta swallows.
AB  - Many animals use photoperiod cues to synchronize reproduction with environmental
      conditions and thereby improve their reproductive success. The circadian clock,
      which creates endogenous behavioral and physiological rhythms typically entrained
      to photoperiod, is well characterized at the molecular level. Recent work
      provided evidence for an association between Clock poly-Q length polymorphism and
      latitude and, within a population, an association with the date of laying and the
      length of the incubation period. Despite relatively high overall breeding
      synchrony, the timing of clutch initiation has a large impact on the fitness of
      swallows in the genus Tachycineta. We compared length polymorphism in the Clock
      poly-Q region among five populations from five different Tachycineta species that
      breed across a hemisphere-wide latitudinal gradient (Fig. 1). Clock poly-Q
      variation was not associated with latitude; however, there was an association
      between Clock poly-Q allele diversity and the degree of clutch size decline
      within breeding seasons. We did not find evidence for an association between
      Clock poly-Q variation and date of clutch initiation in for any of the five
      Tachycineta species, nor did we found a relationship between incubation duration
      and Clock genotype. Thus, there is no general association between latitude,
      breeding phenology, and Clock polymorphism in this clade of closely related
      birds.Figure 1Photos of Tachycineta swallows that were used in this study: A) T.
      bicolor from Ithaca, New York, B) T. leucorrhoa from Chascomus, Argentina, C) T.
      albilinea from Hill Bank, Belize, D) T. meyeni from Puerto Varas, Chile, and E)
      T. thalassina from Mono Lake, California, Photographers: B: Valentina Ferretti;
      A, C-E: David Winkler.

PMID- 22408730
TI  - Structural and functional response of methane-consuming microbial communities to
      different flooding regimes in riparian soils.
AB  - Climate change will lead to more extreme precipitation and associated increase of
      flooding events of soils. This can turn these soils from a sink into a source of
      atmospheric methane. The latter will depend on the balance of microbial methane
      production and oxidation. In the present study, the structural and functional
      response of methane oxidizing microbial communities was investigated in a
      riparian flooding gradient. Four sites differing in flooding frequency were
      sampled and soil-physico-chemistry as well as methane oxidizing activities,
      numbers and community composition were assessed. Next to this, the active
      community members were determined by stable isotope probing of lipids. Methane
      consumption as well as population size distinctly increased with flooding
      frequency. All methane consumption parameters (activity, numbers, lipids)
      correlated with soil moisture, organic matter content, and conductivity. Methane
      oxidizing bacteria were present and activated quickly even in seldom flooded
      soils. However, the active species comprised only a few representatives belonging
      to the genera Methylobacter, Methylosarcina, and Methylocystis, the latter being
      active only in permanently or regularly flooded soils.This study demonstrates
      that soils exposed to irregular flooding harbor a very responsive methane
      oxidizing community that has the potential to mitigate methane produced in these
      soils. The number of active species is limited and dominated by one methane
      oxidizing lineage. Knowledge on the characteristics of these microbes is
      necessary to assess the effects of flooding of soils and subsequent methane
      cycling therein.

PMID- 22408731
TI  - Sex-specific genetic variances in life-history and morphological traits of the
      seed beetle Callosobruchus maculatus.
AB  - Knowledge of heritability and genetic correlations are of central importance in
      the study of adaptive trait evolution and genetic constraints. We use a paternal
      half-sib-full-sib breeding design to investigate the genetic architecture of
      three life-history and morphological traits in the seed beetle, Callosobruchus
      maculatus. Heritability was significant for all traits under observation and
      genetic correlations between traits (r(A)) were low. Interestingly, we found
      substantial sex-specific genetic effects and low genetic correlations between
      sexes (r(MF)) in traits that are only moderately (weight at emergence) to
      slightly (longevity) sexually dimorphic. Furthermore, we found an increased sire
      ([Formula: see text]) compared to dam ([Formula: see text]) variance component
      within trait and sex. Our results highlight that the genetic architecture even of
      the same trait should not be assumed to be the same for males and females.
      Furthermore, it raises the issue of the presence of unnoticed environmental
      effects that may inflate estimates of heritability. Overall, our study stresses
      the fact that estimates of quantitative genetic parameters are not only
      population, time, environment, but also sex specific. Thus, extrapolation between
      sexes and studies should be treated with caution.

PMID- 22408732
TI  - Locus-specific view of flax domestication history.
AB  - Crop domestication has been inferred genetically from neutral markers and
      increasingly from specific domestication-associated loci. However, some crops are
      utilized for multiple purposes that may or may not be reflected in a single
      domestication-associated locus. One such example is cultivated flax (Linum
      usitatissimum L.), the earliest oil and fiber crop, for which domestication
      history remains poorly understood. Oil composition of cultivated flax and pale
      flax (L. bienne Mill.) indicates that the sad2 locus is a candidate domestication
      locus associated with increased unsaturated fatty acid production in cultivated
      flax. A phylogenetic analysis of the sad2 locus in 43 pale and 70 cultivated flax
      accessions established a complex domestication history for flax that has not been
      observed previously. The analysis supports an early, independent domestication of
      a primitive flax lineage, in which the loss of seed dispersal through capsular
      indehiscence was not established, but increased oil content was likely occurred.
      A subsequent flax domestication process occurred that probably involved multiple
      domestications and includes lineages that contain oil, fiber, and winter
      varieties. In agreement with previous studies, oil rather than fiber varieties
      occupy basal phylogenetic positions. The data support multiple paths of flax
      domestication for oil-associated traits before selection of the other
      domestication-associated traits of seed dispersal loss and fiber production. The
      sad2 locus is less revealing about the origin of winter tolerance. In this case,
      a single domestication-associated locus is informative about the history of
      domesticated forms with the associated trait while partially informative on forms
      less associated with the trait.

PMID- 22408733
TI  - Northern refugia and recent expansion in the North Sea: the case of the wrasse
      Symphodus melops (Linnaeus, 1758).
AB  - Pleistocene climate changes have imposed extreme conditions to intertidal rocky
      marine communities, forcing many species to significant range shifts in their
      geographical distributions. Phylogeographic analyses based on both mitochondrial
      and nuclear genetic markers provide a useful approach to unravel phylogeographic
      patterns and processes of species after this time period, to gain general
      knowledge of how climatic changes affect shifts in species distributions. We
      analyzed these patterns on the corkwing wrasse (Symphodus melops, Labridae), a
      rocky shore species inhabiting North Sea waters and temperate northeastern
      Atlantic Ocean from Norway to Morocco including the Azores, using a fragment of
      the mitochondrial control region and the first intron of the nuclear S7 ribosomal
      protein gene. We found that S. melops shows a clear differentiation between the
      Atlantic and the Scandinavian populations and a sharp contrast in the genetic
      diversity, high in the south and low in the north. Within each of these main
      geographic areas there is little or no genetic differentiation. The species may
      have persisted throughout the last glacial maximum in the southern areas as
      paleotemperatures were not lower than they are today in North Scandinavia. The
      North Sea recolonization most likely took place during the current interglacial
      and is dominated by a haplotype absent from the south of the study area, but
      present in Plymouth and Belfast. The possibility of a glacial refugium in or near
      the English Channel is discussed.

PMID- 22408734
TI  - Impact of historical founder effects and a recent bottleneck on MHC variability
      in Commander Arctic foxes (Vulpes lagopus).
AB  - Populations of Arctic foxes (Vulpes lagopus) have been isolated on two of the
      Commander Islands (Bering and Mednyi) from the circumpolar distributed mainland
      population since the Pleistocene. In 1970-1980, an epizootic outbreak of mange
      caused a severe population decline on Mednyi Island. Genes of the major
      histocompatibility complex (MHC) play a primary role in infectious disease
      resistance. The main objectives of our study were to compare contemporary
      variation of MHC class II in mainland and island Arctic foxes, and to document
      the effects of the isolation and the recent bottleneck on MHC polymorphism by
      analyzing samples from historical and contemporary Arctic foxes. In 184
      individuals, we found 25 unique MHC class II DRB and DQB alleles, and identified
      evidence of balancing selection maintaining allelic lineages over time at both
      loci. Twenty different MHC alleles were observed in mainland foxes and eight in
      Bering Island foxes. The historical Mednyi population contained five alleles and
      all contemporary individuals were monomorphic at both DRB and DQB. Our data
      indicate that despite positive and diversifying selection leading to elevated
      rates of amino acid replacement in functionally important antigen-binding sites,
      below a certain population size, balancing selection may not be strong enough to
      maintain genetic diversity in functionally important genes. This may have
      important fitness consequences and might explain the high pathogen susceptibility
      in some island populations. This is the first study that compares MHC diversity
      before and after a bottleneck in a wild canid population using DNA from museum
      samples.

PMID- 22408735
TI  - Phenotypic covariance structure and its divergence for acoustic mate attraction
      signals among four cricket species.
AB  - The phenotypic variance-covariance matrix (P) describes the multivariate
      distribution of a population in phenotypic space, providing direct insight into
      the appropriateness of measured traits within the context of multicollinearity
      (i.e., do they describe any significant variance that is independent of other
      traits), and whether trait covariances restrict the combinations of phenotypes
      available to selection. Given the importance of P, it is therefore surprising
      that phenotypic covariances are seldom jointly analyzed and that the
      dimensionality of P has rarely been investigated in a rigorous statistical
      framework. Here, we used a repeated measures approach to quantify P separately
      for populations of four cricket species using seven acoustic signaling traits
      thought to enhance mate attraction. P was of full or almost full dimensionality
      in all four species, indicating that all traits conveyed some information that
      was independent of the other traits, and that phenotypic trait covariances do not
      constrain the combinations of signaling traits available to selection. P also
      differed significantly among species, although the dominant axis of phenotypic
      variation (p(max)) was largely shared among three of the species (Acheta
      domesticus, Gryllus assimilis, G. texensis), but different in the fourth (G.
      veletis). In G. veletis and A. domesticus, but not G. assimilis and G. texensis,
      p(max) was correlated with body size, while p(max) was not correlated with
      residual mass (a condition measure) in any of the species. This study reveals the
      importance of jointly analyzing phenotypic traits.

PMID- 22408736
TI  - Simulated climate change conditions unveil the toxic potential of the fungicide
      pyrimethanil on the midge Chironomus riparius: a multigeneration experiment.
AB  - Although it has been suggested that temperature increase may alter the toxic
      potential of environmental pollutants, few studies have investigated the
      potential risk of chemical stressors for wildlife under Global Climate Change
      (GCC) impact. We applied a bifactorial multigeneration study in order to test if
      GCC conditions alter the effects of low pesticide concentrations on life history
      and genetic diversity of the aquatic model organism Chironomus riparius.
      Experimental populations of the species were chronically exposed to a low
      concentration of the fungicide pyrimethanil (half of the no-observed-adverse
      effect concentration: NOAEC/2) under two dynamic present-day temperature
      simulations (11.0-22.7 degrees C; 14.0-25.2 degrees C) and one future scenario
      (16.5-28.1 degrees C). During the 140-day multigeneration study, survival,
      emergence, reproduction, population growth, and genetic diversity of C. riparius
      were analyzed. Our results reveal that high temperature and pyrimethanil act
      synergistically on the midge C. riparius. In simulated present-day scenarios, a
      NOAEC/2 of pyrimethanil as derived from a life-cycle toxicity test provoked only
      slight-to-moderate beneficial or adverse effects on C. riparius. In contrast,
      exposure to a NOAEC/2 concentration of pyrimethanil at a thermal situation likely
      for a summer under GCC conditions uncovered adverse effects on mortality and
      population growth rate. In addition, genetic diversity was considerably reduced
      by pyrimethanil in the future scenario, but only slightly under current climatic
      conditions. Our multigeneration study under near-natural (climatic) conditions
      indicates that not only the impact of climate change, but also low concentrations
      of pesticides may pose a reasonable risk for aquatic insects in future.

PMID- 22408737
TI  - Chloroplast genome sequence confirms distinctness of Australian and Asian wild
      rice.
AB  - Cultivated rice (Oryza sativa) is an AA genome Oryza species that was most likely
      domesticated from wild populations of O. rufipogon in Asia. O. rufipogon and O.
      meridionalis are the only AA genome species found within Australia and occur as
      widespread populations across northern Australia. The chloroplast genome sequence
      of O. rufipogon from Asia and Australia and O. meridionalis and O. australiensis
      (an Australian member of the genus very distant from O. sativa) was obtained by
      massively parallel sequencing and compared with the chloroplast genome sequence
      of domesticated O. sativa. Oryza australiensis differed in more than 850 sites
      single nucleotide polymorphism or indel from each of the other samples. The other
      wild rice species had only around 100 differences relative to cultivated rice.
      The chloroplast genomes of Australian O. rufipogon and O. meridionalis were
      closely related with only 32 differences. The Asian O. rufipogon chloroplast
      genome (with only 68 differences) was closer to O. sativa than the Australian
      taxa (both with more than 100 differences). The chloroplast sequences emphasize
      the genetic distinctness of the Australian populations and their potential as a
      source of novel rice germplasm. The Australian O. rufipogon may be a perennial
      form of O. meridionalis.

PMID- 22408738
TI  - Life history traits variation in heterogeneous environment: The case of a
      freshwater snail resistance to pond drying.
AB  - Ecologists and population geneticists have long suspected that the diversity of
      living organisms was connected to the structure of their environment. In
      heterogeneous environments, diversifying selection combined to restricted gene
      flow may indeed lead to locally adapted populations. The freshwater snail, Galba
      truncatula, is a good model to address this question because it is present in a
      heterogeneous environment composed of temporary and permanent waters. In order to
      test the selective importance of those environments, we proposed here to measure
      survival of lineages from both habitats during drought episodes. To this purpose,
      we experimentally submitted adults and juveniles individuals from both habitats
      to drought. We found a difference in desiccation resistance between temporary and
      permanents waters only for adults. Adults from temporary habitats were found more
      resistant to drought. This divergence in desiccation resistance seems to explain
      the unexpected life history traits differences between habitats observed.

PMID- 22408739
TI  - Pheromone production, male abundance, body size, and the evolution of elaborate
      antennae in moths.
AB  - The males of some species of moths possess elaborate feathery antennae. It is
      widely assumed that these striking morphological features have evolved through
      selection for males with greater sensitivity to the female sex pheromone, which
      is typically released in minute quantities. Accordingly, females of species in
      which males have elaborate (i.e., pectinate, bipectinate, or quadripectinate)
      antennae should produce the smallest quantities of pheromone. Alternatively,
      antennal morphology may be associated with the chemical properties of the
      pheromone components, with elaborate antennae being associated with pheromones
      that diffuse more quickly (i.e., have lower molecular weights). Finally, antennal
      morphology may reflect population structure, with low population abundance
      selecting for higher sensitivity and hence more elaborate antennae. We conducted
      a phylogenetic comparative analysis to test these explanations using pheromone
      chemical data and trapping data for 152 moth species. Elaborate antennae are
      associated with larger body size (longer forewing length), which suggests a
      biological cost that smaller moth species cannot bear. Body size is also
      positively correlated with pheromone titre and negatively correlated with
      population abundance (estimated by male abundance). Removing the effects of body
      size revealed no association between the shape of antennae and either pheromone
      titre, male abundance, or mean molecular weight of the pheromone components.
      However, among species with elaborate antennae, longer antennae were typically
      associated with lower male abundances and pheromone compounds with lower
      molecular weight, suggesting that male distribution and a more rapidly diffusing
      female sex pheromone may influence the size but not the general shape of male
      antennae.

PMID- 22408740
TI  - Improbable but true: the invasive inbreeding ambrosia beetle Xylosandrus
      morigerus has generalist genotypes.
AB  - The wide distribution and dominance of invasive inbreeding species in many forest
      ecosystems seems paradoxical in face of their limited genetic variation.
      Successful establishment of invasive species in new areas is nevertheless
      facilitated by clonal reproduction: parthenogenesis, regular self-fertilization,
      and regular inbreeding. The success of clonal lineages in variable environments
      has been explained by two models, the frozen niche variation (FNV) model and the
      general-purpose genotype (GPG) model. We tested these models on a widely
      distributed forest pest that has been recently established in Costa Rica-the
      sibling-mating ambrosia beetle Xylosandrus morigerus. Two deeply diverged
      mitochondrial haplotypes coexist at multiple sites in Costa Rica. We find that
      these two haplotypes do not differ in their associations with ecological factors.
      Overall the two haplotypes showed complete overlap in their resource utilization;
      both genotypes have broad niches, supporting the GPG model. Thus, probable or
      not, our findings suggest that X. morigerus is a true ecological generalist.
      Clonal aspects of reproduction coupled with broad niches are doubtless important
      factors in the successful colonization of new habitats in distant regions.

PMID- 22408741
TI  - Regulatory versus coding signatures of natural selection in a candidate gene
      involved in the adaptive divergence of whitefish species pairs (Coregonus spp.).
AB  - While gene expression divergence is known to be involved in adaptive phenotypic
      divergence and speciation, the relative importance of regulatory and structural
      evolution of genes is poorly understood. A recent next-generation sequencing
      experiment allowed identifying candidate genes potentially involved in the
      ongoing speciation of sympatric dwarf and normal lake whitefish (Coregonus
      clupeaformis), such as cytosolic malate dehydrogenase (MDH1), which showed both
      significant expression and sequence divergence. The main goal of this study was
      to investigate into more details the signatures of natural selection in the
      regulatory and coding sequences of MDH1 in lake whitefish and test for
      parallelism of these signatures with other coregonine species. Sequencing of the
      two regions in 118 fish from four sympatric pairs of whitefish and two cisco
      species revealed a total of 35 single nucleotide polymorphisms (SNPs), with more
      genetic diversity in European compared to North American coregonine species.
      While the coding region was found to be under purifying selection, an SNP in the
      proximal promoter exhibited significant allele frequency divergence in a parallel
      manner among independent sympatric pairs of North American lake whitefish and
      European whitefish (C. lavaretus). According to transcription factor binding
      simulation for 22 regulatory haplotypes of MDH1, putative binding profiles were
      fairly conserved among species, except for the region around this SNP. Moreover,
      we found evidence for the role of this SNP in the regulation of MDH1 expression
      level. Overall, these results provide further evidence for the role of natural
      selection in gene regulation evolution among whitefish species pairs and suggest
      its possible link with patterns of phenotypic diversity observed in coregonine
      species.

PMID- 22408744
TI  - Non-bismuth quadruple therapy for first-line Helicobacter pylori eradication: A
      randomized study in Japan.
AB  - AIM: To find the way to improve the eradication rate of first-line therapy in
      Japanese patients. METHODS: We prospectively compared the effectiveness of 7-d
      quadruple therapy to standard 7 d triple therapy in Japanese patients infected
      with Helicobacter pylori (H. pylori). One hundred and nineteen patients were
      randomly assigned to receive 7-d non-bismuth quadruple therapy with lansoprazole,
      amoxicillin, clarithromycin and metronidazole (LACM7) or 7-d triple therapy with
      lansoprazole, amoxicillin and clarithromycin (LAC7). After three months, H.
      pylori status was analyzed by (13)C-urea breath test. Incidence rates of adverse
      events were evaluated by use of questionnaires. RESULTS: By intention-to-treat
      (ITT) analysis, the eradication rate in the LACM7 group was 94.9%, which was
      significantly higher than the LAC7 group (68.3%, P < 0.001). Per protocol
      analysis also showed a significantly higher eradication rate in the LACM7 group
      (98.3%) than the LAC7 group (73.2%, P < 0.001). Nevertheless, the incidence of
      serious adverse events did not differ between the two groups (RR: 1.10, 95% CI:
      0.70-1.73, P = 0.67). CONCLUSION: Seven day non-bismuth quadruple therapy (LACM7)
      was superior to standard 7-d triple therapy (LAC7) for first-line eradication.

PMID- 22408743
TI  - The Roles of the Paf1 Complex and Associated Histone Modifications in Regulating
      Gene Expression.
AB  - The conserved Paf1 complex (Paf1C) carries out multiple functions during
      transcription by RNA polymerase (pol) II, and these functions are required for
      the proper expression of numerous genes in yeast and metazoans. In the elongation
      stage of the transcription cycle, the Paf1C associates with RNA pol II, interacts
      with other transcription elongation factors, and facilitates modifications to the
      chromatin template. At the end of elongation, the Paf1C plays an important role
      in the termination of RNA pol II transcripts and the recruitment of proteins
      required for proper RNA 3' end formation. Significantly, defects in the Paf1C are
      associated with several human diseases. In this paper, we summarize current
      knowledge on the roles of the Paf1C in RNA pol II transcription.

PMID- 22408747
TI  - Investigation of multichannel phased array performance for fetal MR imaging on
      1.5T clinical MR system.
AB  - Fetal MRI on 1.5T clinical scanner has been increasingly becoming a powerful
      imaging tool for studying fetal brain abnormalities in vivo. Due to limited
      availability of dedicated fetal phased arrays, commercial torso or cardiac phased
      arrays are routinely used for fetal scans, which are unable to provide optimized
      SNR and parallel imaging performance with a small number coil elements, and
      insufficient coverage and filling factor. This poses a demand for the
      investigation and development of dedicated and efficient radiofrequency (RF)
      hardware to improve fetal imaging. In this work, an investigational approach to
      simulate the performance of multichannel flexible phased arrays is proposed to
      find a better solution to fetal MR imaging. A 32 channel fetal array is presented
      to increase coil sensitivity, coverage and parallel imaging performance. The
      electromagnetic field distribution of each element of the fetal array is
      numerically simulated by using finite-difference time-domain (FDTD) method. The
      array performance, including B(1) coverage, parallel reconstructed images and
      artifact power, is then theoretically calculated and compared with the torso
      array. Study results show that the proposed array is capable of increasing B(1)
      field strength as well as sensitivity homogeneity in the entire area of uterus.
      This would ensure high quality imaging regardless of the location of the fetus in
      the uterus. In addition, the paralleling imaging performance of the proposed
      fetal array is validated by using artifact power comparison with torso array.
      These results demonstrate the feasibility of the 32 channel flexible array for
      fetal MR imaging at 1.5T.

PMID- 22408748
TI  - Fashion or Science? How Can Orthodox Biomedicine Explain the Body's Function and
      Regulation?
AB  - The cost of diagnosing and treating disease continues to rise inexorably. Almost
      every new test adds to the complexity and cost of healthcare. There is a need for
      better and less expensive screening, diagnostic and scanning techniques. Medical
      scanning technologies are based upon the body's response to an external stimulus
      e.g. heat, ultrasound, X-rays, magnetic resonance, etc. Biomarker and
      histopathology tests have inherent limitations because diseases are often
      polygenic and/or influence the function of multiple physiological systems. The
      results are compared with expected norms. This makes it difficult to diagnose the
      onset of disease. Such techniques measure only what the clinician wants or
      expects to see. A technique which can provide more information, regarding the
      influence of a medical condition upon the body's whole function, may be
      invaluable to the clinician. There is not yet a clear understanding of how the
      body regulates its function. A greater understanding of how the body responds to
      sensory input, in particular to light, has been incorporated into a mathematical
      model of the physiological systems developed by I.G. Grakov. This has been
      incorporated into a cognitive technology which improves the understanding of how
      the body regulates its function and has led to the development of a better method
      for the diagnosis and treatment of disease(s). This technique, virtual scanning,
      appears able to diagnose at different levels of physiological significance i.e.
      as systems, organs, cells (as morphologies) and molecular (as pathologies). It
      may be a major scientific development, conceivably more advanced than biomarker
      techniques, with the potential to provide far more information about a patient's
      health. It may have the potential to significantly reduce the complexity and cost
      of healthcare. This article reviews the available literature.

PMID- 22408745
TI  - Forebrain glutamatergic neurons mediate leptin action on depression-like
      behaviors and synaptic depression.
AB  - The glutamatergic system has been implicated in the pathophysiology of depression
      and the mechanism of action of antidepressants. Leptin, an adipocyte-derived
      hormone, has antidepressant-like properties. However, the functional role of
      leptin receptor (Lepr) signaling in glutamatergic neurons remains to be
      elucidated. In this study, we generated conditional knockout mice in which the
      long form of Lepr was ablated selectively in glutamatergic neurons located in the
      forebrain structures, including the hippocampus and prefrontal cortex (Lepr cKO).
      Lepr cKO mice exhibit normal growth and body weight. Behavioral characterization
      of Lepr cKO mice reveals depression-like behavioral deficits, including
      anhedonia, behavioral despair, enhanced learned helplessness and social
      withdrawal, with no evident signs of anxiety. In addition, loss of Lepr in
      forebrain glutamatergic neurons facilitates NMDA-induced hippocampal long-term
      synaptic depression (LTD), whereas conventional LTD or long-term potentiation
      (LTP) was not affected. The facilitated LTD induction requires activation of the
      GluN2B subunit as it was completely blocked by a selective GluN2B antagonist.
      Moreover, Lepr cKO mice are highly sensitive to the antidepressant-like
      behavioral effects of the GluN2B antagonist but resistant to leptin. These
      results support important roles for Lepr signaling in glutamatergic neurons in
      regulating depression-related behaviors and modulating excitatory synaptic
      strength, suggesting a possible association between synaptic depression and
      behavioral manifestations of depression.

PMID- 22408746
TI  - TGF-beta receptor II loss promotes mammary carcinoma progression by Th17
      dependent mechanisms.
AB  - We report that IL-17 significantly increases the secretion of CXCL1 and CXCL5
      from mammary carcinoma cells, which is downregulated by TGF-beta through the type
      II TGF-beta receptor (TbetaRII). Carcinoma cells with conditional knockout of
      TbetaRII (Tgfbr2(KO)) have enhanced sensitivity to IL-17a in the stimulation of
      chemokine secretion. During polyoma middle T (PyMT) induced tumor progression,
      levels of Th17 inducing cytokines TGF-beta, IL-6, IL-23 were increased in
      PyMT/Tgfbr2(KO) tumors, which was associated with an increased number of Th17
      cells. IL-17 increased the suppressive function of MDSCs on T cells through the
      upregulation of Arg, IDO, and COX2. Treatment of PyMT/Tgfbr2(KO) mice with anti
      IL-17 Ab decreased carcinoma growth and metastatic burden. Analysis of human
      breast cancer transcriptome databases showed a strong association between IL-17
      gene expression and poor outcome in lymph node positive, estrogen receptor
      negative or luminal B subtypes suggesting potential therapeutic approaches.

PMID- 22408749
TI  - Clinical highlights in the treatment of pancreatic diseases.
AB  - Despite advances in the treatment of pancreatic diseases, they remain clinical
      challenges. In this review article, the author summarized the key abstracts
      presented at 9(th) Congress of the European Hepato-Pancreato-Biliary Association,
      held in Cape Town, South Africa, from April 12(th) to 16(th), 2011. These studies
      include the endoscopy, surgery, complications, and other clinical points of the
      pancreatic treatment.

PMID- 22408750
TI  - Medication adherence and its determinants among patients on concomitant
      tuberculosis and antiretroviral therapy in South west ethiopia.
AB  - BACKGROUND: To benefit from therapy and to avoid contracting treatment resistant
      strains, the individuals must adhere to medications. AIM: The study was designed
      to assess the degree of drug adherence and its determinants in patients living
      with HIV/AIDS and TB comorbidity. MATERIALS AND METHODS: A cross-sectional study
      was conducted to assess the degree of drug adherence and its determinants with
      the help of self-administered questionnaires in Tercha District Hospital in South
      Ethiopia. RESULT: A total of 24 patients were included in the study. The majority
      were females (54.2%) and the mean age was 32.4 (SD+/-9.6) years. Adherence level
      was 95.8% for Antiretroviral (ARV) medications and 79.2% for anti TB medications.
      Educational status was associated with anti TB (P=0.021) medication adherence.
      The reason for the missed doses were mostly lack of money for transport (23.7%
      for antiretroviral therapy (ART), 26.0% for TB treatment) and forgetting to take
      medications (18.4% for ART, 17.4% for TB treatment. CONCLUSION: The adherence
      level obtained for both ARV and anti-TB where high. Transportation costs for
      patients could be reduced by bringing the services close to where they live.

PMID- 22408751
TI  - Pregnant women and non-steroidal anti-inflammatory drugs: knowledge, perception
      and drug consumption pattern during pregnancy in ethiopia.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the widely
      used drugs and are often used by pregnant women. However, they can have
      significant teratogenic effects. The aim of the study was to investigate pregnant
      women's knowledge about NSAIDs use during pregnancy and their perception and
      consumption pattern. MATERIALS AND METHODS: The study was a cross sectional study
      on women waiting for a consultation in the selected maternity hospitals in Addis
      Ababa, Ethiopia. The pregnant women were selected randomly and then interviewed
      by using standardized questionnaires. RESULT: A total of 224 pregnant women were
      involved in the study. Out of those, 203 (90.6%) of them have taken NSAIDs since
      the beginning of their pregnancy. About 201 (89.7%), 198 (88.4%) and 189 (84.4%)
      of the pregnant women considered that ibuprofen, diclofenac and aspirin are not
      NSAIDs respectively. Regarding analgesic effect of NSAIDs, 97 (43.3%) of the
      pregnant women believed that NSAIDs are effective for treating pain.
      Acetaminophen was considered as the most effective treatment for pain by 84
      (37.50%) of the patients. CONCLUSION: Acetaminophen is the most common analgesic
      that was taken by most pregnant women. The knowledge of pregnant women about
      NSAIDs is poor.

PMID- 22408752
TI  - Carotid artery intima media thickness as a surrogate marker of atherosclerosis in
      patient with chronic renal failure on hemodialysis.
AB  - BACKGROUND: In patients with chronic renal failure (CRF), carotid artery intima
      media thickness (CAIMT) is increased when the patients are on hemodialysis.
      Vascular events caused by atherosclerosis are the major cause of death in
      patients undergoing hemodialysis. AIMS: This study was done to find out the
      relationship between carotid artery intima media thickness and hemodialysis in
      chronic renal failure patients independent of classical risk factors and also the
      relationship between CAIMT of hemodialyzed patients and nonhemodialyzed CRF
      patients. MATERIALS AND METHODS: In this observational study, CAIMT of 78 CRF
      patients was examined by B-mode ultrasonography. Glomerular filtration rate (GFR)
      was calculated by using the "Modification of Diet in Renal Disease" formula. CRF
      patients, who had been on regular hemodialysis treatment (treated thrice weekly)
      for at least 6 months, were identified as hemodialyzed patients. Data were
      analyzed by software Statistical package for the social Sciences (SPSS) (17(th)
      version). RESULTS: There was significant positive correlation between CAIMT and
      hemodialysis (P=0.045) independent of traditional risk factors. Hemodialyzed
      patients had higher mean CAIMT (1136.30+/-21.21 MUm, P<0.001) than mean CAIMT of
      age and sex matched nondialyzed patients (959.30+/-23.01 MUm). CONCLUSION:
      Hemodialysis is an independent risk factor for atherosclerosis in CRF patents.
      Hemodialyzed patients have significantly higher CAIMT than nondialyzed CRF
      patients.

PMID- 22408753
TI  - Minimally invasive total knee arthroplasty: a comparative study to the standard
      approach.
AB  - BACKGROUND: Minimally invasive surgery has gained popularity over the past
      several years. Early results have shown better functional outcome with early
      recovery and rapid rehabilitation. AIM: Evaluation of the short-term clinical and
      functional outcome of minimally invasive surgery total knee arthroplasty (MIS
      TKA) compared with the traditional total knee arthroplasty (TKA). MATERIALS AND
      METHODS: During 2009, all cases scheduled for primary TKA through the modified
      mini-mid-vastus approach (MIS group) were studied. This group included 40 knees
      and was compared to a cohort control group of similar number of patients (40
      knees) that underwent the procedure through the standard conventional technique
      (standard group). RESULTS: Patients in the MIS group showed significant decrease
      in postoperative pain, blood loss in first 24 hours, and in hospital stay.
      Furthermore, they achieved motion considerably faster than the standard group
      with earlier return of quadriceps function and greater early flexion. CONCLUSION:
      This study proved that MIS-TPA has the ability to couple the benefits of less
      invasive surgical approach.

PMID- 22408754
TI  - Vitamin e supplementation with rauwolfia vomitoria root bark extract improves
      hematological indices.
AB  - BACKGROUND: Vitamin supplementation in Rauwolfia vomitoria root bark extract
      administration may interact and impact significantly on hematology of albino
      Wistar rats. AIM: In this investigation we studied vitamin E supplementation with
      Rauwolfia vomitoria root bark extract on the hematology of experimental animals.
      MATERIALS AND METHODS: Forty two rats weighing 200 - 230 g were randomly selected
      into six groups of seven animals each. Group 1 animals serve as controls; group 2
      received vitamin E (10 IU/kg body weight). Groups 3 and 4 were given the extract
      (150 and 300 mg/kg body weight) respectively. Groups 5 and 6 were given vitamin E
      (10 IU/kg body weight), the extract (150 and 300 mg/kg body weight) respectively.
      The extract and the vitamin were administered daily by oral intubation. Blood
      samples analyzed for hematological indices. RESULTS: Decrease in white blood cell
      count (WBC) was observed, indicating improved immunity of animals. Extract at 150
      and 300 mg/kg body weight with and without vitamin E affected hemoglobin and
      packed cell volume. CONCLUSION: Rauwolfia vomitoria with or without vitamin E
      improved animal's immunity and enhances their hematology. Interaction of vitamin
      E with the extract affects medicinal therapeutics of this plant.

PMID- 22408755
TI  - Drug-induced hepatotoxicity in a tertiary care hospital in rural South India.
AB  - BACKGROUND: Liver is the main organ for metabolism of drugs and hepatotoxicity is
      a potential adverse effect for most drugs. AIMS: This study was to study the
      frequency of drug-induced hepatotoxicity and to find the common drugs causing
      hepatotoxicity. MATERIALS AND METHODS: The study was conducted at a tertiary care
      hospital in rural India. It is a study based on case series analysis. All
      patients with an abnormal liver function report, between July 2006 and July 2007,
      were included in the study RESULTS: The study included 411 patients. Among them
      141 patients were females and 270 males. The common cause for abnormal liver
      function was alcoholic liver disease (30.4%) followed by drug-induced
      hepatotoxicity (15.8%) and malaria (15.3%). Drug-induced hepatotoxicity was seen
      in 65 patients. It was common in males (55%) compared to females (44%). The mean
      age of the patients with drug-induced hepatotoxicity was 43+/-15.9.
      Antitubercular drugs were the commonly encountered drugs (44%) causing
      hepatotoxicity followed by lipid lowering agents (41%). The others drugs included
      antiretroviral drugs (6%),steroids (5%) and chlorpromazine (2%). CONCLUSION: A
      thorough history of drug intake must be taken in all patients presenting with
      abnormal hepatic function.

PMID- 22408756
TI  - Prevalence and desire for body contouring surgery in postbariatric patients in
      saudi arabia.
AB  - BACKGROUND: Morbid obesity has become a common problem worldwide and as a result
      the demand for bariatric surgery has increased as well. Most patients develop
      skin redundancy and sagging at many body parts after major weight loss procedures
      which increased the demand for body contouring procedures. AIMS: The study was to
      address the prevalence and patient's desire for body contouring procedures.
      MATERIALS AND METHODS: A cross-sectional study targeting the postbariatric
      patients from April 2011 to October 2011 was conducted at our hospital.
      Questionnaire was administered in order to measure frequency and patients desire
      to undergo body contouring surgery after massive weight loss. RESULTS: The total
      number of patients was 128 patients. The mean age of our patients was 37-year old
      (range 18-56 year). The percentage of the desire for body contouring surgery
      after bariatric surgery was 78.1%. There was very pronounced desire to body
      contouring surgery after those who underwent gastric bypass surgery with P-value
      0.001. Only 18 patients (14%) have underwent body contouring surgery, with a
      total of 29 procedures, in which abdominoplasty considered the most commonly
      procedure performed (57%). CONCLUSION: With the increasing number of weight loss
      surgery, there is higher number of patients that desire a body contouring
      surgery, which create huge disparity between demand and accessibility.

PMID- 22408757
TI  - Early determination of human immunodeficiency virus status by routine voluntary
      counseling and testing in benin city, Nigeria.
AB  - BACKGROUND: To reduce the burden of human immunodeficiency virus (HIV), the
      popularization of voluntary counseling and testing (VCT) for early determination
      of human immunodeficiency virus status will be of immense benefit. AIM: To
      evaluate the uptake of voluntary counseling and testing and sero-prevalence of
      human immunodeficiency virus among status naive outpatients and self-presenting
      VCT clients in Benin City, Nigeria. MATERIALS AND METHODS: This study was carried
      out in the period of May 2010 to April 2011 at the University of Benin teaching
      hospital, Benin City. Subjects who consented were included and screened for HIV.
      Pre and post-test counseling was done following the world health organization
      guidelines. RESULTS: Out of 10,533 subjects (7783 outpatients and 2750 self
      presenting VCT clients) counseled for VCT, a total of 4651(44.2%) subjects;
      (3971(51.0%) outpatients and 680 (24.7%) self-presenting VCT clients), consented
      and accepted HIV VCT. Overall HIV prevalence was 6.4%. 270 (6.8%) outpatients and
      29 (4.3%) self-presenting VCT clients were HIV positive. HIV was significantly
      associated with female gender among the outpatients (P<0.001). CONCLUSION: VCT
      uptake was low; the sero-prevalence of HIV was high. The need to employ an
      expanded and more purpose oriented public enlightenment campaign on the
      usefulness of HIV VCT should be a priority for HIV control agencies in our area.

PMID- 22408758
TI  - Unusual case of acute renal failure following multiple wasp stings.
AB  - The wasp stings usually cause local reactions and rarely anaphylaxis. However the
      multiple wasp stings may cause multisystem involvement. We report a case of acute
      renal failure (ARF) following multiple wasp stings. A middle aged healthy
      gentleman presented with pain and swelling of the upper part of the body
      following multiple wasp stings. After 2 days, he developed progressive decrease
      in urine output with high colored urine. Physical examination revealed the
      edematous and tender affected part. On investigating, it was found to have
      sequential elevations in renal function tests. The markers of muscle injury were
      grossly elevated and liver enzymes were deranged. These findings suggest
      multisystem involvement predominantly ARF secondary to rhabdomyolysis. With the
      initiation of the intense hemodialysis, all the above parameters became normal.
      Timely intervention of multiple wasp stings causing ARF with multiorgan
      involvement by hemodialysis not only prevents mortality but also other
      complications.

PMID- 22408759
TI  - HIV and Anemia Among Pregnant.

PMID- 22408760
TI  - Importance of reporting age-adjusted prevalence in epidemiological studies.

PMID- 22408761
TI  - Fostering Youth Engagement on Community Teams.
AB  - Within the youth development field a growing movement exists to establish youth
      member positions on community teams (e.g. organizational boards and planning
      committees). The involvement of youth on decision-making teams is commonly
      referred to as youth engagement. As a relatively new approach to youth and
      community development, the existing research shows the potential positive impacts
      youth engagement efforts may produce and encourages youth practitioners to
      incorporate such efforts into their programs and organizations. In doing so,
      successful youth engagement efforts may be sustained within teams that best adapt
      their organizational structure, policies, and practices to complement the
      developmental needs of youth. Such adaptations begin with the four team
      characteristics presented in this paper: adult support, a youth-friendly
      environment, opportunities to complete meaningful tasks, and opportunities to
      learn and use new skills. When these practices are woven through the work of the
      team, youth engagement may flourish.

PMID- 22408762
TI  - Clinical significance of autoantibodies to p53 protein in patients with
      autoimmune liver diseases.
AB  - BACKGROUND: Autoantibodies to p53 (anti-p53) are rarely present in the sera of
      patients with autoimmune diseases or the sera of patients with malignancies.
      OBJECTIVE: To examine the prevalence of anti-p53 in patients with autoimmune
      liver disease including autoimmune hepatitis (AIH), primary biliary cirrhosis
      (PBC), AIH/PBC overlap syndrome (AIH/PBC OS) and primary sclerosing cholangitis
      (PSC), and to determine the clinical significance of anti-p53 in autoimmune liver
      diseases. METHODS: Forty patients with AIH, 41 patients with PBC, eight patients
      with AIH/PBC OS and five patients with PSC were enrolled. Anti-p53 and antibodies
      to double-stranded DNA (anti-ds-DNA) were analyzed using commercially available
      ELISA kits. Demographic, laboratory and histological data were compared between
      the AIH groups seropositive and seronegative for anti-p53. RESULTS: Six of 40
      (15.0%) patients with AIH and four of eight (50.0%) patients with AIH/PBC OS were
      positive for anti-p53. One of 41 (2.4%) patients with PBC was also positive for
      anti-p53, but all five patients with PSC were negative, indicating a
      significantly higher prevalence of anti-p53 in patients with AIH or AIH/PBC OS
      compared with patients with PBC. None of the AIH patients positive for anti-p53
      progressed to hepatic failure or relapsed after immunosuppressive treatment.
      Titres of anti-ds-DNA in patients with AIH and AIH/PBC OS significantly
      correlated with titres of anti-p53 (r=0.511; P=0.0213). CONCLUSION: The emergence
      of anti-p53 is likely to be useful for discriminating AIH or AIH/PBC OS from PBC
      and helpful for predicting favourable prognoses in patients with AIH. DNA damage
      may trigger the production of anti-p53 in patients with AIH or AIH/PBC OS.

PMID- 22408763
TI  - FIT to be tried.

PMID- 22408764
TI  - Fecal immunochemical tests compared with guaiac fecal occult blood tests for
      population-based colorectal cancer screening.
AB  - Colorectal cancer (CRC) is the second most common cause of cancer deaths in
      Canadian men and women - accounting for almost 12% of all cancer deaths. In
      Ontario, it is estimated that 8100 persons were diagnosed with CRC in 2011, and
      3250 died from the disease. CRC incidence and mortality rates in Ontario are
      among the highest in the world. Screening offers the best opportunity to reduce
      this burden of disease. The present report describes the findings and
      recommendations of Cancer Care Ontario's Fecal Immunochemical Tests (FIT)
      Guidelines Expert Panel, which was convened in September 2010 by the Program in
      Evidence-Based Care. The purpose of the present guideline is to evaluate the
      existing evidence concerning FIT to inform the decision on how to replace the
      current guaiac fecal occult blood test with FIT in the Ontario ColonCancerCheck
      Program. Eleven articles were included in the present guideline, comprising two
      systematic reviews, five articles reporting on three randomized controlled
      trials, and reports of four other studies. Additionally, one laboratory study was
      obtained that reported on several parameters of FIT tests that helped to inform
      the present recommendation. The performance of FIT is superior to the standard
      guaiac fecal occult blood test in terms of screening participation rates and the
      detection of CRC and advanced adenoma. Given greater specimen instability with
      the use of FIT, a pilot study should be undertaken to determine how to implement
      the FIT in Ontario.

PMID- 22408765
TI  - Reassessing the role for lamivudine in chronic hepatitis B infection: a four-year
      cohort analysis.
AB  - BACKGROUND/ OBJECTIVES: Lamivudine is readily available and inexpensive.
      Guidelines recommend other antiviral medications because they achieve superior
      virological suppression with less resistance. These data are based on clinical
      trial populations and may not be representative of typical hepatitis B virus
      (HBV) populations. The authors assessed lamivudine in maintaining long-term viral
      suppression in an adherent, frequently monitored, noninvestigational HBV-infected
      population. METHODS: All HBV patients (n=369) between 2000 and 2010 were
      evaluated in a retrospective, single-centre study. Virological response was
      defined by complete suppression of HBV DNA (<400 copies/mL) and was assessed at
      six to 12 month intervals over four years. Enzymatic and serological outcomes, as
      well as treatment failures were assessed. RESULTS: Forty-seven patients (36 men;
      mean age 44 years, mean alanine aminotransferase level 123 U/L; METAVIR stage 3/4
      [n=21], treatment naive [n=41]) received lamivudine 100 mg to 300 mg daily. The
      mean pretreatment viremia was 5.19 log10 copies/mL, and was above the limit of
      detection (>6.91 log10 copies/mL) in 11 patients (23%). The mean (+/- SD) dosing
      duration was 32+/-22 months. Virological suppression was achieved in 45 (96%)
      patients. Mean viremia declined to 3.06 log10 copies/mL (n=27) and 2.68 log10
      copies/mL (n=18) at 12 and 48 months, respectively, with 78% and 88% with
      undetectable viremia at these time points, respectively. The mean alanine
      aminotransferase level declined to 31 U/L and 36 U/L at 12 and 48 months,
      respectively. Seven of 13 (54%) hepatitis B e antigen-positive patients
      seroconverted. The treatment failure rate was 11%. CONCLUSIONS: In a selected
      group of HBV patients, successful long-term viremia suppression was achieved with
      low treatment failure rates. With strict dosing adherence and monitoring for
      virological breakthrough, sustained virological suppression can be reliably
      achieved with lamivudine in carefully selected patients.

PMID- 22408768
TI  - Primary references for the gingival graft procedure: a note of clarification.

PMID- 22408767
TI  - The utility of Xenon-133 liver scan in the diagnosis and management of
      nonalcoholic fatty liver disease.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an important and common
      condition affecting approximately 20% of the general population. Given the
      limitation of radiological investigations, diagnosis often requires a liver
      biopsy. OBJECTIVE: To compare Xenon-133 (Xe-133) liver scanning with
      ultrasonography in the diagnosis of NAFLD. METHODS: From January 2003 to February
      2007, 258 consecutive patients with suspected NAFLD underwent Xe-133 liver
      scanning at Royal Victoria Hospital (Montreal, Quebec). Of these, 43 patients
      underwent ultrasonography and liver biopsy for the evaluation of NAFLD. Patients
      with other liver diseases and significant alcohol consumption were excluded. Two
      nuclear medicine physicians assessed liver Xe-133 uptake and measured the grade
      of steatosis using a standardized protocol. The degree of steatosis was
      determined from biopsy specimens assessed by two hepatopathologists. RESULTS:
      NAFLD was identified by liver biopsy in 35 of 43 patients (81.4%). Xe-133 scan
      demonstrated 94.3% sensitivity (95% CI 81.4% to 98.4%) and 87.5% specificity (95%
      CI 52.9% to 99.4%) for the presence of NAFLD. The positive and negative
      predictive values for detection of steatosis by Xe-133 scan were 97.1% (95% CI
      85.1% to 99.8%) and 77.8% (95% CI 45.3% to 93.7%), respectively. The positive and
      negative likelihood ratios were 7.54 (95% CI 1.20 to 47.26) and 0.07 (95% CI 0.02
      to 0.26), respectively. Two patients with NAFLD (5.7%) who had a negative Xe-133
      scan result had histologically mild steatosis (<10%). The grade of steatosis on
      liver biopsy was highly correlated with the results of the Xe-133 scan (r=0.87;
      P<0.001). The sensitivity and specificity of ultrasound in diagnosing steatosis
      were 62.9% and 75%, respectively. CONCLUSION: Xe-133 liver scan proved to be a
      safe, reliable, noninvasive method for diagnosing and quantifying hepatic
      steatosis, and was superior to ultrasound.

PMID- 22408766
TI  - Safety of esophagogastroduodenoscopy within 30 days of myocardial infarction: a
      retrospective cohort study from a Canadian tertiary centre.
AB  - BACKGROUND: Patients who experience myocardial infarction (MI) are at risk of
      gastrointestinal (GI) bleeding complications. Endoscopic evaluation may lead to
      cardiopulmonary complications. Guidelines and studies regarding the safety of
      endoscopy in this population are limited. OBJECTIVE: To evaluate the safety of
      endoscopy in a retrospective cohort of post-MI patients at a Canadian tertiary
      centre. METHODS: Using hospital diagnostic/procedure codes, the charts of
      patients meeting the inclusion criteria of having ST elevation MI or non-ST
      elevation MI, and GI bleeding detected at endoscopy were reviewed. The
      information retrieved included demographics, medical history, medications,
      endoscopy details and cardiopulmonary/GI events. RESULTS: A total of 121 patients
      experienced an MI and underwent endoscopy within 30 days. However, only 44 met
      the inclusion criteria and were reviewed. The mean age of the patients was 75
      years, and 55% were female. The mean hemoglobin level was 86 g/L, and 38 of 44
      patients required a transfusion. Comorbidities included hypertension (82%),
      diabetes (46%), heart failure (55%), stroke (21%), lung disease (27%), previous
      MI (46%), cardiac bypass surgery (30%), history of GI bleed (25%), history of
      ulcer (18%) and ejection fraction <50% (48%). The median number of days to
      endoscopy after MI was three. Complications included seven patients with acute
      coronary syndrome, one with arrhythmia, one with respiratory failure, one with
      aspiration pneumonia and two with perforation. Age, hemoglobin level or timing of
      endoscopy did not significantly predict a complication. CONCLUSIONS: Patients
      with GI bleeding after MI often have comorbidities and are on antiplatelet
      agents. Endoscopy is a valuable tool in the diagnosis and management of bleeding
      complications, but must be weighed against the potential risk of other
      complications, which in the present study occurred in more than 25% of
      procedures.

PMID- 22408769
TI  - The effect of cigarette smoking and native bone height on dental implants placed
      immediately in sinuses grafted by hydraulic condensation.
AB  - The purpose of this study was to determine the effect of cigarette smoking and
      residual native bone height on the survival of dental implants placed immediately
      in grafted sinuses. In this retrospective study, 334 subject records were
      screened, and 75 subjects (155 implants) were included. Data collection based on
      treatment notes and radiographs included age, sex, smoking status, sinus floor
      bone height, dental implant information, and implant survival. The survival rates
      of implants for nonsmokers and smokers at stage-two surgery were 93% and 84%,
      respectively. After 12 months of functional loading, the survival rates of
      implants for nonsmokers and smokers were 87% (81 of 93) and 79% (49 of 62),
      respectively (P < .000). Analysis revealed that the effect of smoking on implant
      survival is significant when the preoperative bone height is less than 4 mm, with
      an 82.4% implant survival rate in nonsmokers compared to 60% in smokers (P <
      .05). Smoking should be considered as a high risk factor when implants are placed
      immediately in grafted sinuses, particularly in areas of limited bone height.

PMID- 22408770
TI  - Growth factor-mediated combination therapy to treat large local human alveolar
      ridge defects.
AB  - The purpose of this case report is to demonstrate the effectiveness of a matrix
      consisting of recombinant human platelet-derived growth factor BB (rhPDGF-BB)
      hydrated cancellous allogenic block graft in the reconstruction of large local
      human alveolar ridge defects. The results suggest improved bone regeneration when
      combining rhPDGF-BB with the allogenic block graft. The clinical and histologic
      evidence of new bone formation as well as bone remodeling supports the clinical
      potency of this growth factor-mediated therapy.

PMID- 22408771
TI  - Ankylosis of nonresorbable hydroxyapatite graft material as a contributing factor
      in recurrent periodontitis.
AB  - Many studies have shown that alloplastic bone grafts are clinically stable and
      safe. Nevertheless, postoperative problems such as ankylosis and root resorption
      are associated with alloplastic bone grafts. This report examined two cases of
      ankylosis of nonresorbable hydroxyapatite (NHA) alloplastic grafts associated
      with recurrent periodontitis. There was no clear border between the NHA particles
      and dentin. The particles were irregularly shaped and had plaque on the surfaces.
      It is postulated that ankylosis of NHA particles and dentin is a contributing
      factor in recurrent periodontitis.

PMID- 22408772
TI  - Evaluation of a resorbable collagen matrix infused with rhPDGF-BB in peri-implant
      soft tissue augmentation: a preliminary report with 3.5 years of observation.
AB  - Soft tissue augmentation around dental implants in the esthetic region remains a
      challenging and unpredictable procedure. The ideal surgical technique would
      include of an off-the-shelf product to minimize morbidity after autogenous
      grafting procedures. The aim of this study was to use a resorbable collagen
      matrix (Mucograft) to serve as a scaffold to recombinant human platelet-derived
      growth factor BB (rhPDGF-BB) to increase peri-implant soft tissue volume in
      anterior maxillary sites. A total of six patients who had previously undergone a
      bone regeneration procedure were included in this study. The collagen matrix was
      applied during stage-two surgery (expanded polytetrafluoroethylene membrane
      removal and implant placement). Measurements were performed through customized
      stents by means of endodontic files, and at abutment connection, a soft tissue
      biopsy specimen was harvested for histologic examination. The healing period was
      uneventful in all six patients. Measurements were taken apically, centrally, and
      occlusally for each site. The mean gains in volume from baseline to the 4-month
      measurement at the apical, central, and occlusal aspects were 0.87 +/- 2.13 mm,
      2.14 +/- 3.27 mm, and 0.35 +/- 3.20 mm, respectively. The results showed a
      moderate increase in the soft tissue volume in esthetic peri-implant sites when
      applying a collagen matrix infused with rhPDGF-BB. However, the measuring
      techniques available need to be further improved to record exact changes in the
      soft tissue volume.

PMID- 22408773
TI  - GDF-5 and BMP-2 regulate bone cell differentiation by gene expression of MSX1,
      MSX2, Dlx5, and Runx2 and influence OCN gene expression in vitro.
AB  - Recombinant human growth/differentiation factor 5 (rhGDF-5) and recombinant human
      bone morphogenetic protein 2 (rhBMP-2), as members of the transforming growth
      factor Beta family, influence bone formation and differentiation. This in vitro
      osteoblast cell culture study investigated the molecular biologic effect of these
      growth factors on regulator gene expression of the homebox proteins MSX1 and MSX2
      as well as distal-less homebox 5 (Dlx5) and runt-related transcription factor 2
      (Runx2/Cbfa1). Concerning effector genes, the messenger ribonucleic acids of
      osteocalcin (OCN) were quantified using a reverse transcriptase real-time
      polymerase chain reaction. Over a period of 15 days, osteoblasts were stimulated
      and analyzed at days 1, 2, 5, 10, and 15. rhGDF-5 and rhBMP-2 were applied in
      concentrations of 100, 500, and 1,000 ng/mL. The results showed enhanced gene
      expression of MSX1 and MSX2 by the lower rhGDF-5 concentration (100 ng/mL) during
      the first 48 hours and a marginally enhanced gene expression of Runx2 and OCN in
      a dose-dependent manner. The rhBMP-2 stimulation showed enhanced MSX1 and MSX2
      gene expression with peaks at 24 and 240 hours; Runx2 and OCN were more highly
      expressed than the unstimulated control with the 100-ng/mL concentration. rhGDF-5
      seems to stimulate early osteoblast differentiation and extracellular matrix
      production, while rhBMP-2 seems to boost early and late osteoblast
      differentiation. Low growth factor concentrations appeared to be more effective
      in terms of gene expression.

PMID- 22408774
TI  - High temperature-treated bovine porous hydroxyapatite in sinus augmentation
      procedures: a case report.
AB  - Among the graft materials that can be used clinically, xenografts are the most
      common. Xenografts are of bovine, porcine, or equine origin and require the
      complete removal of proteins to avoid immunologic problems and the risk of
      transmission of prions, viruses, etc. Protein destruction can be achieved by a
      chemical procedure using organic solvents and heat treatment. After this process,
      a carbonated hydroxyapatite similar to human bone remains. The aim of this case
      report is to investigate the bone formation in a sinus augmentation procedure
      using a high temperature-treated bovine porous hydroxyapatite. A 58-year-old
      woman underwent bilateral sinus augmentation using this biomaterial. After 9
      months, during stage-two surgery, two core biopsy specimens were retrieved and
      treated to obtain thin ground undecalcified sections. Microscopically, newly
      formed bone was present at the interface with most particles. The major portion
      of the particles appeared to be completely lined and surrounded by bone. No
      obvious signs of resorption were present on the biomaterial surface. No gaps or
      connective tissue were present at the bone-biomaterial interface. No inflammatory
      infiltrate or fibrous encapsulation of the particles was present.
      Histomorphometry showed that the percentages of newly formed bone, residual
      grafted particles, and marrow spaces were 25.1% +/- 2.3%, 37.3% +/- 1.1%, and
      38.5% +/- 3.1%, respectively. The excellent properties demonstrated by Endobon
      are probably a result of its particular hydroxyapatite porous microstructure with
      a high percentage of interconnected micropores that promote the ingrowth of
      osteogenic cells and vessels, making graft integration easier and faster.

PMID- 22408775
TI  - Clinical evaluation of the effectiveness of different bleaching therapies in
      vital teeth.
AB  - The aims of this in vivo study were to compare the effectiveness and color
      stability of at-home and in-office bleaching techniques and to evaluate whether
      the use of light sources can alter bleaching results. According to preestablished
      criteria, 40 patients were selected and randomly divided into four groups
      according to bleaching treatment: (1) at-home bleaching with 10% carbamide
      peroxide, (2) in-office bleaching with 35% hydrogen peroxide (HP) without a light
      source, (3) in-office bleaching with 35% HP with quartz-tungsten-halogen light,
      and (4) in-office bleaching with 35% HP with a light-emitting diode/laser. Tooth
      shade was evaluated using the VITA Classical Shade Guide before bleaching as well
      as after the first and third weeks of bleaching. Tooth shade was evaluated again
      using the same guide 1 and 6 months after the completion of treatment. The shade
      guide was arranged to yield scores that were used for statistical comparison.
      Statistical analysis using the Kruskal-Wallis test showed no significant
      differences among the groups for any time point (P > .01). There was no color
      rebound in any of the groups. The bleaching techniques tested were equally
      effective. Light sources are unnecessary to bleach teeth.

PMID- 22408776
TI  - Periosteal pocket flap for horizontal bone regeneration: a case series.
AB  - Guided bone regeneration has been shown to be a successful technique to increase
      the ridge width for dental implant placement. However, in cases of severe or
      localized horizontal bone deficiencies, achieving sufficient soft tissue
      mobilization to ensure primary wound closure over the augmented area can be
      difficult. This article describes a buccal periosteal pocket flap proposed to
      overcome these challenges. The flap design results in a periosteal pocket, which
      allows filling of bone-grafting material while facilitating primary tension-free
      soft tissue closure by splitting of the mucosa. The flap gives stability to the
      augmented volume within the pocket. Ridge widths of five patients consecutively
      treated with this technique were recorded before and 24 weeks after augmentation.
      Results from these cases showed a mean 389% +/- 301% gain in bone width (range,
      50% to 1,420%) when the periosteal pocket flap design was used. Data obtained
      from this study suggest that the periosteal pocket flap design could be a
      predictable alternative flap approach for correction of severe or localized
      horizontal bone deficiencies.

PMID- 22408777
TI  - Peri-implant collagen fibers around human cone Morse connection implants under
      polarized light: a report of three cases.
AB  - Most of the histologic studies found in the literature on the peri-implant soft
      tissues have been done in animals and usually have been confined to mandibular
      implants fitted with healing or standard abutments. Few studies have investigated
      human peri-implant soft tissues. Moreover, the structure and dimensions of the
      peri-implant soft tissues in immediately loaded implants have not been
      investigated in depth. Human histologic data are valuable to validate animal
      models. This histologic and histomorphometric study evaluated the peri-implant
      soft tissues around three immediately loaded implants in humans. The implants
      were retrieved using a trephine and treated to obtain thin, ground sections. The
      sulcular epithelium was composed of approximately four to five layers of
      parakeratinized epithelial cells and had a length of approximately 1.2 to 1.3 mm.
      The junctional epithelium was composed of approximately three to four layers of
      epithelial cells and had a length of approximately 1.0 to 1.5 mm. Connective
      tissue attachment had a width of between 400 and 800 MUm. Peri-implant collagen
      fibers, in the form of bundles (1- to 5-MUm thick), began at the crestal bone and
      were oriented perpendicular to the abutment surface until 200 MUm from the
      surface, where they became parallel running in several directions. Collagen
      fibers appeared to form a three-dimensional network around the abutment. No acute
      or chronic inflammatory cell infiltrate was present. Collagen fibers oriented in
      a perpendicular manner and in direct contact with the abutment surface were not
      observed in any of the specimens. This differentiated network of fibers may have
      clinical relevance as a mechanical protection of the underlying bone. These human
      histologic data are extremely valuable to validate and confirm those obtained
      from studies performed on animal models. Moreover, immediate loading of the
      implants did not compromise soft tissue integration.

PMID- 22408778
TI  - Alternative method to fabricating an immediately loaded mandibular hybrid
      prosthesis without impressions: a clinical report.
AB  - Immediate loading procedures may cause discomfort to the patient and increase the
      possibility of damage to the surgical site during prosthetic restorations. The
      aim of this clinical report is to describe an alternative method to fabricating a
      mandibular hybrid prosthesis in 3 days without taking an impression. Five
      implants were placed in the anterior region of an edentulous mandible and
      restored with a definitive mandibular hybrid prosthesis using a unique acrylic
      resin framework. This acrylic resin framework enabled the fabrication of the
      metal framework of the mandibular hybrid prosthesis without taking a final
      impression. The step-by-step technique is described.

PMID- 22408779
TI  - Bone density around endosseous implants in patients taking alendronate: a pilot
      study.
AB  - The purpose of this blind, randomized, controlled pilot investigation was to
      noninvasively determine bone mineral density (BMD) changes around endosseous
      implants placed in healthy patients who were administered the oral
      aminobisphosphonate alendronate. BMD was analyzed using computed tomography (CT)
      and grayscale imaging. Male patients (62 +/- 12 years of age) were selected for
      placement of implants in a two-stage protocol. Patients requiring implants were
      initially seen for placement of half the total number of implants unilaterally in
      the maxilla or mandible, and each patient underwent a baseline CT scan. Six
      months from baseline, contralateral implants were placed with randomization into
      groups receiving 70 mg of alendronate weekly or a placebo, and a second CT scan
      was completed. Alendronate/placebo was discontinued after 6 months, and a CT scan
      was completed at 12 months. Patients returned for an exit evaluation and CT scan
      at 18 months. Hounsfield units were measured at implant placement and nonsurgical
      sites in the maxilla and mandible. Within the limitations of this study, results
      included: a decreasing trend in BMD surrounding an implant when alendronate was
      administered for 6 months starting at the time of implant placement, a less
      evident decreasing trend in BMD surrounding an implant when alendronate was
      administered for 6 months after the implant had successfully undergone
      osseointegration, and a trend suggesting BMD "rebound" when alendronate was
      discontinued for 6 months after initial drug administration starting either at
      the time of implant placement or after the implant had successfully undergone
      osseointegration for 6 months.

PMID- 22408780
TI  - Osteotome versus conventional drilling technique for implant site preparation: a
      comparative study in the rabbit.
AB  - The aim of this research was to study the influence of the osteotome technique on
      insertion torque and stability values when compared with conventional surgical
      drilling of the implant site. A total of 20 implants (4-mm diameter, 8.5-mm long)
      were placed in the distal femural condyle of 10 New Zealand White rabbits. The
      implant sites were prepared by using either the conventional drilling technique
      as a control group (group A) or the osteotome technique (group B). Cutting torque
      and resonance frequency analyses (RFAs) were conducted at and after implant
      placement. The resulting values were subjected to correlation and comparative
      analyses between groups. Insertion torque measurements were conducted at three
      different levels of implant insertion: crestal, middle, and apical. Group B
      showed higher mean insertion torque and RFA values (P < .05). No statistically
      significant correlation could be observed when comparing the mean torque values
      with RFA values (P > .05). Bone condensation before implant insertion in low
      density bone led to higher mean insertion torque and RFA values. Within the
      limits of this experimental study, a benefit in using the osteotome technique was
      observed when dealing with low-density bone. Bone condensation can improve
      primary stabilization of implants.

PMID- 22408781
TI  - Pouch roll technique for implant soft tissue augmentation: a variation of the
      modified roll technique.
AB  - This paper presents three cases of peri-implant mucosal defects that were
      successfully treated with a newly proposed "pouch roll" implant soft tissue
      augmentation technique. This procedure uses a de-epithelialized connective tissue
      layer during the first or second stage of implant surgery over the underlying
      dental implant without the need for sutures. At 2 weeks, healing was remarkable,
      with excellent plaque control. At 3 months, only minimal tissue shrinkage was
      evident. As a result, a 2- to 3-mm increase in the width of the keratinized
      tissue was noted around the augmented implant site. This technique is an
      atraumatic, versatile, and cost-effective surgical modality that enhances the
      peri-implant soft tissue over the ridge with a soft tissue thickness >= 3 mm. The
      pouch roll implant soft tissue augmentation procedure provides an easy and less
      traumatic correction of a mild to moderate buccal ridge deficiency by thickening
      the soft tissue around the dental implant.

PMID- 22408782
TI  - Mandibular reconstruction with tissue engineering in multiple recurrent
      ameloblastoma.
AB  - The aim of this paper is to present a new approach to bone regeneration in a
      patient with multiple recurrent ameloblastoma of the left mandibular angle.
      Through an extraoral approach, complete resection of the tumor was achieved. Bone
      marrow aspirate from the iliac crest was centrifuged to concentrate the
      mesenchymal cellular fraction. Based on a stereolithographic cast, titanium mesh
      was bent preoperatively to accurately reconstruct the mandibular angle. The mesh
      was filled with two blocks of xenogenic material mixed with recombinant bone
      morphogenetic protein 7 (BMP-7) and stem cells. Nine months later, three
      endosseous implants were placed in the regenerated bone to restore the patient's
      masticatory function. At this time, bone samples were obtained for
      histomorphometric analysis. New bone formation was confirmed around the particles
      of xenograft material. The results indicate that adequate esthetics and function
      may be achieved with bone marrow aspirate seeded on a scaffold obtained from
      bovine xenograft blocks and BMP-7. This technique attains new bone formation with
      sufficient quantity and quality to allow for implant placement, with decreased
      patient morbidity and surgical time compared to conventional reconstructive
      methods.

PMID- 22408783
TI  - Clinical wear rate of direct and indirect posterior composite resin restorations.
AB  - The purpose of this randomized clinical trial was to determine the clinical wear
      behavior of three nanofilled composites (Filtek Supreme XT [FS], Tetric EvoCeram
      [TEC], and Aelite Aesthetic [AA]) with two indirect composites (Estenia [E] and
      Tescera ATL [TATL]) on permanent molar teeth. Fifty-four patients whose treatment
      plans included moderate Class I and/or II restorations on molar teeth were
      selected for inclusion in this study. Wear was measured by use of gypsum replicas
      at baseline and 6 and 12 months using three-dimensional scanning and rapid-form
      software to elucidate the wear mechanisms. For statistical analyses, one-way
      analysis of variance and the Scheffe test were used. Statistical results revealed
      that wear behavior of TATL was significantly different from that of AA (P < .05).
      No significant differences were detected between AA and E (P > .05) or between
      TEC, FS, and TATL composite resins (P > .05). The results showed similar clinical
      performance between the five composite resins evaluated. Therefore, composite
      resins may be indicated for the restoration of posterior teeth. However, the
      composition of the composite resin did affect the wear behavior of the composite
      material.

PMID- 22408784
TI  - Effect of postpolymerization method on the color stability of composite resins
      submitted to ultraviolet aging.
AB  - The aim of this research was to evaluate the effect of postpolymerization method
      on the color stability of resin-based composites. Samples of direct and indirect
      restorative materials were polymerized with two photo-curing units (Visio photo
      curing oven system and LED Elipar Freelight 2). All samples were submitted to an
      initial chromatic analysis using a spectrometer and submitted to ultraviolet
      accelerated artificial aging. The direct material showed less color change than
      the indirect material, independent of the photo-activation method used. Samples
      photo cured with the LED system showed less change than those photo cured with
      the Visio system. The postpolymerization oven did not improve the color stability
      of direct and indirect resin-based composites.

PMID- 22408785
TI  - Abstracts of the 11th Biennial Congress of the Latin American Society for Sexual
      Medicine. Buenos Aires, Argentina. September 8-11, 2011.

PMID- 22408786
TI  - Abstracts of the 13th Biennial Meeting of the Asia-Pacific Society for Sexual
      Medicine. Kaohsiung, Taiwan. November 16-20, 2011.

PMID- 22408787
TI  - Modelling of the nanoscale.

PMID- 22408788
TI  - Expert commentary. Teaching case: severe headache in a leukemic.

PMID- 22408789
TI  - Retraction for Johnston and Siderovski. Structural basis for nucleotide exchange
      on Galphai subunits and receptor coupling specificity.

PMID- 22408790
TI  - The life and legacy of Alfred M. Prince, M. D. (1928-2011).

PMID- 22408791
TI  - Stamps of greatness. Dr Wladyslaw Bieganski (1857-1917).

PMID- 22408792
TI  - Stamps of greatness. Sir David Bruce (1885-1931).

PMID- 22408793
TI  - Should doctors feel able to practised according to their personal values and
      beliefs?

PMID- 22408794
TI  - [Cardiac electrode as a cause of the chronic sternal ostheomyelitis].
AB  - Results of the diagnostic concept and treatment of 5 patients with the chronic
      sternal ostheomyelitis after the open cardiac surgery caused by the "forgotten"
      cardiac electrodes were analyzed in the article. The radiologic diagnostic
      criteria and necessity of the computed tomography, in particular, were stated.

PMID- 22408795
TI  - [The distal pancreatic resection with spleen preservation: which collaterals can
      we rely on?].
AB  - The spleen preservation by distal pancreatic resection can be performed either
      with spleen vessels preservation or with the ligation of the least. The
      experiment evolved ligation of all gastric arteries but the short gastric
      arteries in 20 cadaveric organocomplexes, followed by ink perfusion through the
      left gastric and left gastro-epiploic arteries. The study was amplified with the
      intraoperative dopplerography of portal arteries of the spleen after
      crossclamping of the left gastro-epiploic and short gastric arteries. Ten
      patients after distal pancreatic resection with spleen preservation and splenic
      vessels ligation had the CT-angiography before and after the surgery. All the
      conducted studies demonstrated the incapability of short gastric arteries to
      supply the satisfactory spleen perfusion. The left gastro-epiploic artery proved
      to be the main source of splenic blood supply after splenic vessels ligation.

PMID- 22408796
TI  - [The prevention and treatment of the gastroduodenal ulcer bleedings].
AB  - The results of the complex prophylaxis and treatment of 33 458 patients with
      gastric or duodenal ulcer were analyzed. Of the analyzed group, 1002 (2,99%)
      patients experienced ulcer bleeding. The complex out-patient and stationary
      treatment of the ulcer disease allowed of bleeding frequency from 8,6 to 2,1%;
      the decrease of recurrent bleedings from 13,0% to 0; allowed to avoid major
      surgery (the previous frequency was as high as 14,5%) and decreased lethality
      rate from 9 to 1%.

PMID- 22408797
TI  - [The interrelations of the thrombohemorrhagic syndrome and the immune system by
      peritonitis].
AB  - The study aimed the influence of the thrombohemorrhagic syndrome (THS) on the
      immune system in conditions of peritonitis of various severity. The study
      included 120 patients. Main indicators of the cell and humoral immunity were
      correlated with I-III degree of the immune system disorders, which, in turn, was
      correlated with the peritonitis stage. The study proved the importance and
      necessity of the immune correction in patients with severe peritonitis.

PMID- 22408798
TI  - [The Roux reconstruction for the correction of postresectional and
      postgastrectomy syndromes].
AB  - The study substantiates the efficacy of the Roux reconstruction of the upper
      gastrointestinal tract in the surgical treatment of postresectional and
      postgastrectomic syndromes. Such reconstructive operations were performed in 16
      patients. There were no postoperative mortality or specific complications
      registered. The short and long-term follow up demonstrated good compensation of
      the disorders, caused by the earlier radical gastric surgery. Thus, the method of
      the Roux reconstruction, amplified by the creation of functionally active
      sphincters and valves provides the satisfactory relief of the operated stomach
      disease.

PMID- 22408799
TI  - [Diagnostics and treatment of retroperitoneal abscess].
AB  - Etiology of retroperitoneal abscess and flegmona were analyzed in 12 patients.
      The radiological diagnostic capacities in detection of septic process in
      retroperitoneal adipose tissue were explored. Features of surgical treatment,
      depending on the abscess localization were described in detail.

PMID- 22408800
TI  - [The immunogistochemical aspects of the angiogenesis by Ewing's sarcoma].
AB  - Results of observation were analyzed in 68 patients with Ewing's sarcoma.
      Reagents made by DAKO (France) such as CD-31, endothelial cell, clone JC 70A,
      isotype: Lg GI, kappa 02/1 ml were used in the study. It was estimated, that CD31
      expression activity in endothelial elements was inversely proportional and
      reliably correlated with malignant process by the Ewing's sarcoma. Indices of
      lymphoid infiltration in pathological focus were inversely proportional to the
      expression of CD-31 positive cells. Statistically reliable inversely proportional
      relationship was revealed between CD-31 expression of endothelial cells and
      spontaneous tissue necrotization in the Ewing's sarcoma. Reliable direct
      correlation was ascertained between tumor angiogenesis and amount of CD-31.

PMID- 22408801
TI  - [The surgical treatment of the inborn lobar emphysema in children: the
      comparative analysis].
AB  - Results of surgical treatment were comparatively analyzed in children with
      congenital lobar emphysema operated using traditional technique (1 group, 10
      patients) and operated using thoracoscopic technique (2 group, 10 patients). In
      the first group average time of operation amounted 68 +/- 5,8 min., average time
      of plural drainage--3,3 days, average time of postoperative hospitalization--13,6
      days and in the second group--62 +/- 15,6 min., 1,3 days and 7,4 days
      respectively. In the second group postoperative complications were not observed.
      In postoperative period one patient from the first group developed pneumothorax
      eliminated on the 5-th day after operation. Results of investigation indicate the
      advantages of thoracoscopic technique in treatment of children with lobar
      emphysema compared with traditional methods of treatment. Application of
      thoracoscopic technique in children with lobar emphysema is a serious alternative
      to traditional method due to slight postoperative period, lesser amount of
      complications and good cosmetic and functional results.

PMID- 22408802
TI  - [Computer modeling in surgical treatment of rectum cancer].
AB  - 154 patients with rectal cancer were divided into the main group and the control
      group. All of them were investigated using endorectal and intraoperative
      sonography, spiral computer tomography and magnetic resonance tomography. Basing
      on the data of radial diagnostics pelvis model with tumour projection into
      rectum, bladder, ureters, prostate, uterus and vagina was recieved in all
      patients from the main group using Power SHAPE programm. Application of modern
      radial techniques and 3D modeling in diagnostics of rectal cancer contributes to
      adequate extent of surgical treatment adjacent with increased amount of radical
      operations (from 50% to 81,5%) and improvement of prognosis and survival rate in
      postoperative period.

PMID- 22408803
TI  - [The closed injuries of the lower urinary tract: problems of the X-ray
      diagnostics].
AB  - The closed injuries of the lower urinary tract: problems of the X-ray
      diagnostics. Results of X-ray investigation were analyzed in 54 patients with
      urinary bladder trauma and 23 patients with urethral injuries. There were no
      false conclusions during urography in 23 patients with urethral injuries. In one
      patient urography was carried out in late terms due to the underestimation of
      urether trauma by the time of admission to the hospital. Cystography was carried
      out in 38 out of 54 patients to exclude bladder trauma. Presence of trauma was
      confirmed in 36 (94,7%) cases. False conclusion about the absence of bladder
      rupture was given in 2 (5,26%) cases. Type of rupture was misdiagnosed in 5
      (13,1%) patients leading to increased extent of operation in 1 case. The reasons
      for the false conclusions were misconduction of investigation technique and
      underestimation of the obtained X-ray data.

PMID- 22408804
TI  - [Anemia after renal transplantation].
AB  - The study aimed the estimation of posttransplantant anemia (PTA) frequency
      between the recepients of allogenic kidneys and testing the influence of
      different factors on the anemia development. The study was ased on the analysis
      of 129 patients with ERSD, to whom 129 donor kidneys were grafted. An actuarial
      survival of patients and allografts were calculated. The analysis demonstrated
      that a duration of the pretranplant hemodialysis influences the dynamics of
      hemoglobin level and the red blood cells count. The shorter were the dialysis
      terms, the easier was the anemia to correct. Shorter terms of the pretransplant
      dialysis also correlated with the higher rates of the overall survival after the
      transplantation.

PMID- 22408805
TI  - [The clinical picture, diagnostic and treatment of the acute iliopsoitis].
AB  - The treatment results of the acute iliopsoitis in 29 patients were analyzed. The
      right side inflammation was observed more frequently (n=17). The most common
      infectious agent was the Staphylococcus aureus. The source of the inflammation
      was septic lesions of the lower body, whereas the perdisposal factors were
      considered to be the diabetes mellitus, drug abuse and immunodeficiency. The
      cardinal diagnostic sign of the acute iliopsoitis proved to be the psoas-symptom.
      The main diagnostic instruments were the ultrasound investigation, CT and MRI. 1
      patient was successfully treated conservatively, though the rest 28 demanded
      surgical opening and drainage of m. iliopsoas. The lethality rate was 3,4%. 96,6%
      of the treated patients were successfully cured.

PMID- 22408806
TI  - [The efficacy and safety of the early enteral feeding of surgical patients].

PMID- 22408807
TI  - [Estimation of efficiency reamberin in the correction of endogenous intoxication
      syndrome at the patients with the phlegmonous and gangrenous forms of erysipelas
      on background diabetes mellitus at their surgical treatment].
AB  - The influence of modern detoxic preparation reamberin on indicators of the of
      endogenous intoxication syndrome (EIS)--the level of average molecules, malon
      dialdehyde, cyrcukatiry immune complexes and its fractional composition in blood
      serum of the patients with destructive forms of erysipelas--phlegmonous and
      gangrenous on background diabetes mellitus (DM). It is established that the
      inclusion of reamberin in the complex surgical treatment of destructive forms of
      erysipelas on background DM accelerates the elimination of SEI. From this we can
      recommend the use of reamberin in the complex surgical treatment of complicated
      forms of erysipelas on background DM.

PMID- 22408808
TI  - [Prophylaxis and treatment of postoperative nausea and vomiting].

PMID- 22408809
TI  - [The simultaneous surgical treatment of the abdominal aortic aneurism, calculous
      cholecystitis and inguinal hernia].

PMID- 22408810
TI  - [About the magistral vessels injury].

PMID- 22408811
TI  - [S.S. Yudin. To the 120th anniversary of birth].
AB  - In October, 2011 120 years from the birth day of the great surgeon acad. USSR Ac.
      Med. Sci. S.S. Judin. Article include data on S.S.Judin's work and his life in
      Novosibirsk, new materials of the biography of the great surgeon, original
      photos.

PMID- 22408812
TI  - Understanding grief and loss.  Bereavement shares much in common with depression.

PMID- 22408813
TI  - The normal process of grieving.  People often experience fluctuating emotions for
      months.

PMID- 22408814
TI  - Beyond the five stages of grief.  The bereavement process is seldom linear and
      varies from one person to the next.

PMID- 22408815
TI  - A guide to getting through grief.  Focus on the essentials and try to let people
      know what support you need.

PMID- 22408816
TI  - Coping with complicated grief.  Recognizing when mental health treatment may be
      necessary.

PMID- 22408817
TI  - Handling holidays and difficult times.

PMID- 22408818
TI  - I lost my brother several months ago, and there are days when I still feel
      overpowered by sadness.  Is it normal to grieve this long?

PMID- 22408819
TI  - I always knew I'd feel sad when my father died, but I wasn't expecting to feel so
      angry. I snap at everyone. What's wrong with me?

PMID- 22408820
TI  - Breast cancer metastatic to the gastric wall.
AB  - Most gastric tumours are primary carcinomas, but other tumours, including
      metastatic lesions, may also be seen. The most frequent primary location of a
      gastric metastasis is the breast. We present a case of a 55-year-old woman, in
      whom the mammary primary remained clinically unnoticed, and the patient was
      diagnosed with gastric cancer and treated as such. Only after gastrectomy was the
      proper diagnosis established. Although rare, metastatic carcinoma should be taken
      into account in differential diagnosis of less usual patterns gastric tumours.

PMID- 22408821
TI  - Case description.

PMID- 22408822
TI  - 2011 Annual Meeting of the American Society of Primatologists.

PMID- 22408823
TI  - Late pleistocene deposits at Wretton, Norfolk. I. Ipswichian interglacial
      deposits.
AB  - Interglacial deposits found in the low terrace at Wretton, Norfolk, were formed
      in the zones II and III of the Ipswichian interglacial. The variety of sediments
      found is associated with the fluviatile environments of a meandering river.
      During zone II there was a regional mixed oak forest, with the local development
      of alder carr, fen, reedswamp and open water communities. During zone III the
      regional vegetation was more open and Carpinus became an important woodland tree.
      Locally, fen, reedswamp and open-water communities persisted, but alder carr was
      absent. The plants give some indication that the climate may have been more
      continental than at present, a number of species occurring which are not native
      to the British post-glacial flora but which have a wide distribution on the
      Continent. A brief comparison of the vegetational history is made with that of
      other Ipswichian interglacial sites in England and with the correlative Eemian
      interglacial on the Continent. The interglacial sections at Wretton form one of
      the richest Ipswichian sites for non-marine Mollusca so far found in England. The
      presence of a few more southern or more continental species, not now living in
      England, confirms that the climate was probably slightly warmer than at present,
      at least in summer. Numbers are large enough for satisfactory analysis in almost
      all sections, so that the environmental conclusion they suggest can be checked
      against those deduced from the plants. In general, these conclusions match and
      indicate a series of deposits laid down by a plant-rich Fenland river, a true
      ancestor of the present river Wissey, in its channel and neighbouring parts of
      its floodplain. The occurrence of brackish water species of Mollusca allows
      levels of marine influence to be clearly integrated with the vegetational
      history. Brackish horizons occur between - 1.95 m and +0.45 m O.D. in zone II b
      deposits, giving an indication of sea-level at this stage. The zone III deposits,
      although at a lower level, show no trace of brackish influences and a possible
      oscillation of sea-level is inferred.

PMID- 22408824
TI  - The Late-Weichselian Flora of the Isle of Man.
AB  - The last glacial deposits of the Ballaugh-Kirkmichael area in the north-east of
      the Isle of Man have been investigated by analysis of pollen and macroscopic
      fossils and by radiocarbon dating. Assemblages totalling over 160 taxa of
      vascular plants and mosses have been recorded from strata referred to Late
      Weichselian zones I, II and III. Among the most noteworthy species are 46 not now
      living on the island; these include Dianthus deltoides, Juncus balticus, Lychnis
      viscaria, Ranunculus hyperboreus, Sibbaldia procumbens, Meesia tristicha,
      Helodium blandowii and Polytrichum norvegicum. The vegetation comprised a great
      diversity of communities of open, largely calcareous grassland, snow beds, mires
      both base-rich and base-poor, flushes, freshwater, inundated flats and calcareous
      dunes. Saline conditions are indicated by Glaux maritima and Triglochin maritima.
      Trees were represented only by Betula and the taller shrubs by Juniperus and
      Salix.

PMID- 22408825
TI  - The optic lobes of Lepidoptera.
AB  - Variants of the Golgi-Colonnier (1964) selective silver procedure have been used
      to show up neurons in insect brains. Neural elements are particularly clearly
      impregnated in the optic lobes. Three classes of nerve cells can be
      distinguished; perpendicular (class I), tangential (class II) and amacrine cells
      (class III). There are many types of neurons in each class which together have a
      very wide variety of form. Their components are related to specific strata in the
      optic lobe regions. Short visual cells from the retina terminate in the lamina in
      discrete groups of endings (optic cartridges). Pairs of long visual fibres from
      ommatidia pass through the lamina and end in the medulla. Class I cells link
      these two regions in parallel with the long visual fibres and groups of these
      elements define columns in the medulla. These in turn give rise to small-field
      fibres that project to the lobula complex. Tangential processes intersect the
      parallel arrays of class I cells at characteristic levels. Some are complex in
      form and may invade up to three regions. Another type provides a direct link
      between the ipsi- and contralateral optic lobe. Amacrine cells are intrinsic to
      single lobe regions and have processes situated at the same levels as those of
      classes I and II cells. A fifth optic lobe region, the optic tubercle, is
      connected to the medulla and lobula and also receives a set of processes from the
      mid-brain. There are at least six separate types of small-field relays which
      could represent the retina mosaic arrangement in the lobula.

PMID- 22408826
TI  - The optic lobes of Diptera.
AB  - The optic lobes of Diptera have been examined by variants of the Golgi-Colonnier
      selective staining techniques and by reduced silver procedures. All, bar one, of
      the elements described by the earlier authors (Vigier 1908; Zawarzin 1913; Cajal
      & Sanchez 1915) have been seen, in part or in their entirely, in these
      preparations. Many other forms, hitherto unrecognized, have been found. Their
      perpendicular topographical relationships have been reconstructed in the optic
      lobe regions. Some lateral relationships have also been reconstructed between
      elements in regions whose columnar arrangement is clearly discernible in Golgi
      preparations; these include the lamina and the medulla. In the Diptera the
      projection pattern of the retina mosaic into the lamina neuropil involves complex
      chiasmata between the two regions (Braitenberg 1967); these have been confirmed
      from these species. The retina-lamina mosaic is, essentially, homotopically
      preserved in the columnar medulla, via long visual fibres and monopolar cells.
      The medullary mosaic is preserved through its strata by transmedullary cells and
      the longest small-field amacrine cells. The mosaic is projected to the two
      regions of the lobula complex by class I cells (see part I). The organization of
      the tangential cell processes suggests that some of them may interact with large
      or whole field aggragates of the relayed retinal mosaic. Others, especially in
      the lobula, may interact with small oval or narrow strip-field aggragates.
      Although there are many differences of neural form and number of neurons between
      species, both the Lepidoptera and Diptera have the same fundamental plan of
      neuroarchitecture.

PMID- 22408827
TI  - Further observations on the Lower Devonian Plant, Gosslingia breconensis Heard.
AB  - The first description of this plant was published by Heard (1927). The present
      writer has collected more material from the type locality and has used a
      comparatively new technique on the petrified axes present. This involved sawing
      the axes into thin sections, grinding these smooth with carborundum powder and
      then polishing them in chromic oxide powder. These permanent preparations have
      yielded more precise data on the anatomy of the axes. The spores are described
      for the first time. A reconstruction of the aerial parts of the plant is given.
      The results have been incorporated into an emended diagnosis of the genus and a
      lectotype has been designated. The taxonomic position of Gosslingia is discussed
      in relation to a new classification of the psilophytes proposed by Banks. One of
      the most interesting features in Gosslingia is the axillary tubercle, a small
      protuberance occurring below each dichotomy. A survey of other Devonian plants
      bearing this structure is given and its morphological nature is discussed in the
      light of evidence produced here and in other recent work.

PMID- 22408828
TI  - The fine structure of the digestive tubules of the Marine Bivalve Cardium edule.
AB  - The epithelium lining the digestive tubules of Cardium edule consists of three
      cell types, namely mature digestive cells, mature secretory cells and immature
      flagellated cells. Both the secretory and flagellated cells exhibit a pronounced
      basiphilia and occur in well-defined crypts. The secretory cells are pyramidal in
      shape and characterized by the possession of a well-developed granular
      endoplasmic reticulum and Golgi apparatus. Golgi vesicles derived from the latter
      migrate to the apical region of the cell where they release their contents into
      the lumen of the tubules. It is possible that the secretion contains enzymes and
      although it is likely that such enzymes would function primarily in the lumen of
      the tubules they may also be the source of the weak proteolytic activity which
      has been recorded in the gastric fluid of many bivalves. The immature flagellated
      cells are columnar in shape and possess a poorly developed endoplasmic reticulum
      and numerous free ribosomes. Although no evidence for this was obtained it is
      suggested that they may serve to replace either or both of the mature cell types.
      The digestive cells vary from cuboidal to columnar, possess distinctive Golgi
      elements with characteristic intracisternal membranous elements, and are capable
      of ingesting exogenous material from the lumen of the tubule. The process of
      ingestion was examined following feeding experiments with (a) a mixture of iron
      oxide and colloidal graphite (Aquadag), (b) whole blood from pigeon and (c)
      ferritin. Individual particles of graphite were enclosed in phagosomes by a
      process of phagocytosis, while the proteins haemoglobin and ferritin were
      ingested by a process of pinocytosis; the membrane enclosing the pinocytic
      vesicles possesses a characteristic outer granular coat. The contents of both the
      phagocytic and pinocytic vesicles were transferred to larger bodies considered to
      be primarily phagosomes in the sub-apical regions of the cell. These possess an
      interconnecting system of membrane-bound channels which ramifies through the
      apical cytoplasm. Phagolysosomes deeper in the cytoplasm of the cell were
      identified by the presence of exogenous material and a positive reaction to tests
      for acid phosphatase activity. They showed changes in appearance which could be
      put into a series suggestive of the progressive intracellular digestion of the
      ingested material.

PMID- 22408829
TI  - Organization of the outer plexiform layer of the primate retina: electron
      microscopy of Golgi-impregnated cells.
AB  - Golgi-impregnated retinae of rhesus monkeys have been examined by serial section
      electron microscopy to establish in a quantitative manner the neural connexions
      in the outer plexiform layer. The results have shown that there are two types of
      midget bipolar cell, here called the invaginating midget bipolar and the flat
      midget bipolar. Both types of midget bipolar are exclusive to a single cone. The
      invaginating midget bipolar has been found to fit a dendritic terminal process
      into every invagination in the cone pedicle base. The flat midget bipolar has
      dendritic terminals that make superficial contact on the cone pedicle base. There
      are twice as many dendritic terminals and points of contact with the cone pedicle
      on a flat midget bipolar top as compared with an invaginating midget bipolar top.
      These observations, together with light microscope counts of the numbers of the
      two types of midget bipolars, suggest that there are two midget bipolars per
      cone. The diffuse cone bipolar (the flat bipolar) also makes superficial contacts
      on the cone pedicle base, and serial sections have shown that a flat bipolar
      contacts about six cones. Rod bipolars connect exclusively to rods and their
      dendritic terminals always end as one of the central processes that penetrate the
      invagination. Horizontal cell dendrites end exclusively in cone pedicles and
      their axon terminals end in rod spherules. The point of contact with both the
      types of receptor is as the lateral elements of the invaginations. A single small
      horizontal cell contacts about seven cones and a large horizontal cell contacts
      about twelve cones. The numbers of contacts per cone pedicle decrease from the
      centre to the periphery of the horizontal cell's dendritic field, suggesting
      there is an overlap of four to six horizontal cells onto a single cone pedicle.
      The horizontal cell axon terminals are too numerous to assess in absolute numbers
      but there is only one terminal to a given rod spherule from any particular axon.

PMID- 22408830
TI  - Review lecture: on the organization of reflecting surfaces in some marine
      animals.
AB  - Reflecting surfaces of fish are formed of stacks of thin, flat crystals composed
      of guanine, as the major component, and hypoxanthine, as the minor component. The
      broad surfaces of these crystals are not, in general, parallel to the surfaces in
      which they lie in the fish but they are orientated at angles which depend on the
      function which they serve. The stacks of crystals in different situations also
      differ in the number and thickness of crystals and in spectral reflectivity. The
      organization of these crystals is described, in relation to function, for the
      silvery surfaces of bony fish, the herring and mackerel, for the reflecting
      tapeta found in the shark and dogfish, for the photophores of the deep-sea
      hatchet fish and, finally, for the eye of the scallop.

PMID- 22408831
TI  - Fusimotor innervation in the cat.
AB  - The motor innervation of cat spindles was examined in hindlimb muscles using a
      variety of techniques employed in light and electron microscopy. Observations
      were made on teased, silver preparations of 267 spindles sampled from the
      peroneal, flexor hallucis longus, and soleus muscles, hereafter referred to as
      the PER/FHL/SOL series. The gamma innervation. Trail endings are almost
      invariably present, and innervate both bag and chain muscle fibres. Trail fibres
      accounted for 64.6 to 74.8% of the total fusimotor supply to samples of spindle
      poles in the PER/FHL/SOL series, the mean number of fibres per pole varying from
      2.7 to 5.0 in the different muscles, and the mean number of ramifications (areas
      of synaptic contact) per fibre being 3.7. By contrast, the p2innervation of a
      spindle pole generally consists of a single fibre supplying only one plate. In
      the above samples p(2) fibres accounted for 4.1 to 28.0% of the total fusimotor
      supply, and the mean number of fibres per pole varied from 0.3 to 1.2 in the
      different muscles. Ninety per cent of p(2) plates innervate bag fibres. The alpha
      innervation. The structure of p1plates as seen in both light and electron
      microscopy compares very closely with that of extrafusal plates. After nerve
      section p1plates degenerate at the same time as extrafusal plates, being the
      first of the three types of fusimotor ending to disappear. The frequency of the
      p1innervation is similar to that of the p2innervation. In the same samples of
      PER/FHL/SOL spindle poles as above p1 fibres accounted for 6.0 to 28.8% of the
      total fusimotor supply, the mean number of fibres per pole varying from 0.25 to
      2.1 in the different muscles. The majority of p1 fibres enter a pole to terminate
      in one plate only. Seventy-five per cent of the plates innervate bag fibres. The
      three types of fusimotor ending are thus not selectively distributed to the two
      types of intrafusal muscle fibre. All three types of fusimotor fibre may branch
      within the spindle so as to innervate both bag and chain fibres. Bag fibres
      receive both types of plate ending as well as trail endings. Most chain fibres
      receive trail endings only; the rest receive either a p1or a p2plate innervation
      in addition, 25% of the p1and 10% of the p2innervation being distributed to chain
      fibres. The significance of this nonselective innervation is interpreted as
      indicating that the type of contraction elicited by stimulating a fusimotor fibre
      depends upon the type of ending initiating it rather than upon the type of muscle
      fibre executing it. Reasons are given for concluding that the dynamic response is
      controlled via the p1and p2plates, and that the static response is controlled by
      the trail endings. The participation of the alpha fibres in mammalian fusimotor
      innervation, previously regarded as a vestigial feature, proved to be widespread
      in the muscles studied and more prevalent in fast muscles (FHL, peroneus digiti
      quinti) than slow (soleus). A low frequency of p1innervation is offset by a high
      frequency of p2(as in peroneus longus), and vice versa (as in FHL). It is
      unlikely that collaterals from slow alpha fibres innervating type B muscle fibres
      are wholly responsible for the high frequency of the p1innervation in FHL, and it
      is suggested that collaterals may also be derived from fast alpha fibres
      innervating type C muscle fibres. The possibility of there being some motor
      fibres of alpha conduction velocity and with an exclusively fusimotor
      distribution is also taken into account.

PMID- 22408832
TI  - Late Pleistocene floras from Earith, Huntingdonshire.
AB  - A pit in fluviatile gravel of the River Ouse at the western edge of the East
      Anglian fenland has exposed several richly organic beds of Last-glacial age. A
      radiocarbon date of 42 000 years from one bed confirms the terrace stratigraphy
      in placing the beds in a fairly early part of the Weichselian. The organic beds
      are succeeded by cryoturbation phenomena and ice wedge casts, indicating a
      severely cold climate with permafrost. The beds represent former pools on the
      flood-plain into which plant detritus was washed from the surroundings, chiefly
      by melt water in the spring. Pollen is sparse, but the macroscopic plant remains
      indicate a vegetation dominated by dwarf willows, accompanied by many herbs of
      base-rich, open habitats. Identification of the macrofossils is discussed and
      comments are made on the ecology and taxonomy of important species. The flora
      contains a mixture of northern and southern distributional types, the southern
      including species requiring a July mean temperature approaching 16  degrees C.
      Halophytes are frequent, and four species are considered to be obligate
      halophytes and to demonstrate the presence of salt in the substrate. The plant
      mixtures are explained as a result of the peculiarly open habitats of the glacial
      landscape and of the climate, which appears to have had warm summers and very
      cold winters, with a mean annual temperature slightly below 0  degrees C,
      resulting in discontinuous permafrost.

PMID- 22408833
TI  - The fine structure of the vertical lobe of octopus brain.
AB  - Although much is known about the structural organization and connexions of the
      various lobes of the octopus brain from light microscopy, this is the first
      attempt at a detailed analysis of one of the lobes- the vertical lobe, with the
      electron microscope. The vertical lobe consists of five lobules. The median
      superior frontal (MSF) axons enter each lobule from the MSF lobe. The MSF axons
      contain both microtubules and neurofilaments. The varicosities of the MSF axons
      contain both agranular and dense-cored vesicles and synapse with trunks of the
      amacrine cells. These trunks run together in bundles termed amacrine tracts into
      the centres of the lobules. The amacrine trunks contain microtubules but no
      neurofilaments. The trunks contain large and small agranular synaptic vesicles
      and synapse with what are in all probability branches of the trunks of the large
      cells. These trunks contain microtubules but no neurofilaments. They run out
      through the bases of the lobules probably without forming synaptic contacts
      within the lobule. Fibres signalling 'pain' (nocifensor) enter the lobules from
      below. They can be recognized by their content of neurofilaments. Their terminals
      contain numerous very small synaptic vesicles and a few larger and dense-cored
      ones. These 'pain' fibres appear to synapse mostly with processes of the large
      cells. J. Z. Young has shown that the vertical lobe is especially concerned with
      the integrative action of the visual system, linked with the chemo-tactile
      system. Electron microscopy supports Young's suggestion that the superior frontal
      and interconnected vertical lobe systems constitute a loop which could sustain a
      positive feed-back mechanism (MSF -- amacrine -- large cell -- lateral superior
      frontal -- MSF) while the 'pain' (nocifensor) input could exert a suppressor
      (inhibitory) effect on the loop by its action on the large cells.

PMID- 22408834
TI  - Abstracts of the Fall Meeting 2011 of the Swiss Chemical Society in Lausanne.
      September 9, 2011, Loussanne, Switzerland.

PMID- 22408836
TI  - Abstracts of the International Congress of Clinical Transfusiology, September 23
      25, 2010, Poland.

PMID- 22408835
TI  - Abstracts of the 64th Annual Conference of the Cardiological Society of India,
      December 2-5, 2010, Kolkata, West bengal.

PMID- 22408837
TI  - Abstracts of the International Students' Conference of Medical Sciences. April 22
      24, 2011, Cracow, Poland.

PMID- 22408838
TI  - Abstracts of the 47th Annual Meeting of the Argentine Society for Biochemistry
      and Molecular Biology Research, October 30-September 2, 2011, San Luis,
      Argentina.

PMID- 22408840
TI  - Journal of Law and Medicine: Consolidated index to volumes 1-18, 1993-2011.

PMID- 22408839
TI  - Abstracts of the 20th Annual Research Conference and Workshop on Breath of
      Change: Asthma, Allergy, and Immunology, November 9-11, 2011, Kingston, Jamaica.

PMID- 22408841
TI  - Journal of Law and Medicine. Consolidated index to volumes 1-17. 1993-2010.

PMID- 22408842
TI  - Towards zero transmission of HIV through blood transfusion.

PMID- 22408843
TI  - Health reform: delivery reform.

PMID- 22408844
TI  - Medical errors and patient safety: reducing medical errors and improving patient
      safety.

PMID- 22408845
TI  - Emergency care.

PMID- 22408846
TI  - Developing alternatives to systemic toxicity testing approaches.

PMID- 22408847
TI  - The National Allergy Survey Assessing Limitations (NASAL): materials and
      respondent characteristics.

PMID- 22408848
TI  - [Tobacco: the killers must pay].

PMID- 22408849
TI  - [Topical treatment adherence for psoriasis].

PMID- 22408850
TI  - [Pseudo tumoral textilome discovered twenty five years after laparotomy].

PMID- 22408851
TI  - [Nuclear medicine procedures in paediatric patients].
AB  - The paediatricians rely primarily scintigraphic examinations in two situations:
      when they need functional information to decide operation (measurement of
      separate function of each kidney for example) or when they want to know if a bone
      disease is involved, in front of a sudden onset of musculoskeletal disorder.
      Kidney and bone scan represent 85% of applications for examinations. Some
      scintigraphic examinations have an essential role in the therapeutic evaluation
      and staging of malignancies such as MIBG-123 scintigraphy in neuroblastoma and
      FDG-18F scintigraphy in lymphoma. This presentation would not be complete without
      mentioning some tests whose indications in children are different from adults
      like the lung scan that evaluates separate functions of both lungs in diseases
      such as lung malformations and thyroid scintigraphy performed in cases of
      congenital hypothyroidism to determine the mechanism of this disease. Finally, to
      locate a Meckel's diverticulum in front of a gastrointestinal bleeding. Because
      of its indications, pediatric nuclear medicine concerns a high proportion of very
      young children, and must take into account the specificities of this age.

PMID- 22408852
TI  - [Neurogenic paraosteoarthropathy].

PMID- 22408853
TI  - [Osteoporosis: being able to recognize its severity].

PMID- 22408854
TI  - [Epidemiology of osteoporosis: the incidence of hip fracture decreased].
AB  - Osteoporosis is a frequent disease characterized by a high morbidity. Also a high
      rate of death has ben demonstrated for hip fractures and to a lesser extent for
      vertebral fractures. In the early 90s all the publications showed that the burden
      of fractures due to osteoporosis (and particularly hip fractures) would
      dramatically increase due to an incresed secular trend for the end of the Second
      World War and also due to the increase of life expectancy. However several
      epidemiological studies done in the USA but also in Europe (Scandinavian
      countries but also France) showed that the incidence of fractures and
      particularly hip fractures decreased over time. The hypotheses leading to these
      findings are not fully elucidated. Obviously the development of DXA scans and the
      use of bisphosphonates since the middle of the 90s played a role. Also the
      improvement of lifestyle and the decrease in the use of tobacco and alcohol also
      play a role for explaining these findings. Although these data are very
      encouraging, osteoporosis is still a severe disease characterized by a high rate
      of death. This latter point was demonstrated for hip and vertebral factures but
      also for all the major fractures.

PMID- 22408855
TI  - [Vertebral fractures].
AB  - Vertebral fractures are well-known fragility fractures related to osteoporosis.
      Assessment of secondary osteoporosis and other causes of bone fragility is
      mandatory. Diagnosis of these fractures is relevant, as they are responsible of
      increased morbidity, and even mortality in frail elderly patients. They are a
      strong risk factor for sustaining other fractures, including hip fractures. There
      is a high level of evidence for efficacy of antiosteoporotic treatments in post
      menopausal patients with osteoporosis and vertebral fractures.

PMID- 22408856
TI  - [Osteoporosis: not only the femoral neck fracture].

PMID- 22408857
TI  - [Drug-induced osteoporosis].
AB  - Optimal care of patients at risk of osteoporosis (low bone density and/or
      fracture) requires the assessment of risk factors of osteoporosis and fracture
      (lifestyle risk factors, chronic diseases and drugs). Among drugs, prior and
      current use of oral corticosteroids is strongly associated with an increased risk
      of fractures. But other medications could be involved and should be assessed in
      patients at risk of fractures. There are a strong evidence for GnRH agonists and
      aromatase inhibitors, antiepileptic, selective serotonin reuptake inhibitors,
      proton pump inhibitors. Further studies are necessary to confirm bone deleterious
      effect of other treatments.

PMID- 22408858
TI  - [Osteoporosis secondary to chronic disease].

PMID- 22408859
TI  - [Laboratory tests in osteoporosis].

PMID- 22408861
TI  - [Osteoporosis without fracture: when do we treat?].
AB  - Osteoporosis without prevalent fracture is defined by a low bone mineral density
      (BMD), which is a risk factor for fracture. We also use the FRAX tool to
      determine treatment indications. The objective of the treatment is to reduce
      fracture risk--which has been defined by BMD and clinical risk factors--with
      various types of therapeutic classes, such as bisphosphonates, strontium
      ranelate, denosumab and raloxifene. Calcium and vitamin D may be a useful
      addition.

PMID- 22408860
TI  - [Osteoporosis in men].
AB  - Epidemiologic studies have shown that 25% of osteoporotic fractures occur in men.
      Their prognosis is poor with one third of deaths in the year following the
      proximal femur fracture. Screening is based on the analysis of risk factors
      (prolonged corticosteroid therapy, anti androgen, smoking or alcohol abuse, liver
      disease or chronic inflammatory diseases), taking into account fracture history
      and bone density measurement. The prescription of bisphosphonates or teriparatide
      must be preceded by an etiologic investigation, a withdrawal of bone loss-induced
      drugs (tobacco, alcohol, steroids), a recovery of walking and a specific action
      on fall risk, especially after 70 years.

PMID- 22408862
TI  - [Indications of bone densitometry].

PMID- 22408863
TI  - [Precautions before starting a treatment for osteoporosis].
AB  - To be optimal, the treatment of osteoporosis must be global, including
      nonpharmacological measures. At the initiation of the treatment, a personalized
      evaluation of the patient must be realized on diet, physical activity, risk of
      fall and adhesion of the patient. Dietary calcium is estimated and advices given
      to attain 1000 in 1200 mg/day and limit excessive coffee, soft drinks and salt
      intake. Dietary calcium is recommended, but if it is impossible, a complement is
      prescribed, adapted to the intensity of the deficiency. Serum 25-(OH)-vitamine D
      is measured and, if below 30 ng/ml, a supplementation prescribed. Low protein
      intake is looked for and corrected if necessary. Advises are given to limit the
      alcohol to 2 units/day, stop smoking and to have a regular and high impact
      physical activity. Subjects at risk of fall must be identified and risk factors
      corrected if possible. Dental recommandations for the use of bisphosphonates in
      osteoporosis must be apply. Finally, patient education could be used to optimize
      patient adherence to pharmacological and non pharmacological anti-osteoporotic
      treatments.

PMID- 22408864
TI  - [Vitamin D: dosage and supplementation].

PMID- 22408865
TI  - [Medical treatment of postmenopausal osteoporosis].
AB  - The primary objective of postmenopausal osteoporosis treatment is to reduce the
      risk of fragility fracture. Therefore, the necessary first step is to identify
      patients at high risk of fracture to treat them in the most efficient manner In
      case of patients with a so-called severe fracture including hip fracture,
      vertebral and humeral fracture, characterized by an increased risk of mortality
      in the following years, it is mandatory to treat osteoporosis. In the other cases
      with or without fracture, the decision will rely on clinical fracture risks and
      the result of densitometry assessment. The treatment will be prescribed for a
      first period of 5 years and then reassessed for deciding whether the treatment
      will be continued or interrupted. Reassessments will then be performed regularly.
      When treating is decided, the choice between the different drugs is based on
      their respective ability to reduce the risk of vertebral or non-vertebral
      fracture, their potential extra-skeletal benefits, tolerance and contra
      indications as well as administration conditions which have an impact on
      adherence to treatment. The latter is important to obtain the expected efficacy
      of the treatment and it has to be clearly explained to the patient and controlled
      during follow-up.

PMID- 22408866
TI  - [New therapeutic targets for osteoporosis].

PMID- 22408867
TI  - [Google-like query].

PMID- 22408868
TI  - [Epidemiology and physiopathogy of Sjogren's syndrome].
AB  - Sjogren's syndrome is defined as an autoimmune disease characterized by a
      progressive sicca syndrome associated with anti-SSA or SSA positivity and/or
      significant infiltrate at minor salivary gland biopsy. This autoimmune disease is
      relatively frequent, with a clinical diagnosis among women after the 5 decade.
      Its physiopathology, complex, associates the intervention of both environmental
      and genetic factors. Salivary epithelial cell is at the center of the
      pathological immune response of primary Sjogren's syndrome, characterized by a
      chronic B cell polyclonal activation potentially leading to the development of B
      cell lymphoma.

PMID- 22408869
TI  - [Sjogren's syndrome: diagnosis and systemic manifestations].
AB  - Sjogren's syndrome is an autoimmune exocrinopathy characterized by
      keratoconjunctivis sicca, xerostomia and immune-inflammatory systemic
      manifestations. The diagnosis is easy to establish when the patient presents with
      sicca complex as a main symptom, or recurring attacks of parotitis. However, it
      is way more complex when the disease begins with extraglandular features, such as
      non erosive polyarticular arthritis, Raynaud's phenomenon, peripheral or central
      nervous system involvement, kidney disease or interstitial pneumonary disease, or
      even vasculitis. In such circumstances, diagnosis is often delayed several years.

PMID- 22408870
TI  - [Diagnostic criteria for Sjogren's syndrome].
AB  - Sjodgrens syndrome is a common autoimmune disease with highly variable clinical
      manifestations, making diagnosis difficult and sometimes delayed. Its specific
      clinical presentation combines oral and ocular dryness, asthenia and joint
      involvement. However, visceral involvement and potentially severe complications,
      including lymphoma, are frequently observed. These can be indicative of the
      disease and should lead to consider Sjogren's syndrome as a diagnosis.
      Internationally agreed upon diagnostic criteria were developed to improve the
      ability to make a definitive diagnosis, in order to provide follow-up and
      appropriate treatment measures as early as possible. These criteria, which
      include clinical, laboratory and histological measures, are easy to use in the
      daily practice, and make it possible to rule out the extensive differential
      diagnosis of sicca syndrome.

PMID- 22408871
TI  - [Evolutive forms of primary Sjogren's syndrome].
AB  - Primary Sjogren's syndrome (pSS) could be restricted in 50% of the cases to
      glandular involvement with a chronic sicca syndrome, with a considerable
      alteration of quality of life. It could be complicated by systemic involvements,
      which are responsible of the visceral severity. Thus systemic complications could
      appear many years after initial pSS diagnosis and justify long-term surveillance.
      Initial parotid gland enlargement, Raynaud phenomenon, cutaneous vasculitis and
      immunological abnormalities (anti-SSA and/or SSB positivity,
      hypergammaglobulinemia, and cryoglobulinemia) are also implicated in systemic
      complications.

PMID- 22408872
TI  - [The risk of lymphoma in Sjogren's syndrome].

PMID- 22408873
TI  - [Treatment of primary Sjogren syndrome].
AB  - Treatment of primary Sjogren's syndrome is adapted to the initial evaluation of
      symptom and extraglandular manifestation according to the damage/activity ratio.
      Symptomatic treatment is systematic, whereas systemic treatment is limited to the
      active extra glandular forms. There is no international treatment consensus.
      Biologics are currently evaluated.

PMID- 22408874
TI  - [Treatment of xerophtalmia in Sjogren's syndrome].

PMID- 22408875
TI  - [Primum non nocere].

PMID- 22408876
TI  - [Quincke's oedema or angioedema].

PMID- 22408877
TI  - [Personalized medicine in oncology: from hope to reality].

PMID- 22408878
TI  - [Malignant epithelial and melanocytic skin tumors].

PMID- 22408879
TI  - [HIV infection].

PMID- 22408880
TI  - [Confusional state and disturbances of consciousness].

PMID- 22408881
TI  - [Intracardiac conduction disturbances].

PMID- 22408882
TI  - [Acute leukemia].

PMID- 22408883
TI  - [Medical recollections. The French health service during the war of 1914-1918].

PMID- 22408884
TI  - More than 3,000 pounds sterling.

PMID- 22408885
TI  - 'Dentistry in a decade': recent lessons from the Adult Dental Health Survey.

PMID- 22408886
TI  - Three generations of LED lights and clinical implications for optimizing their
      use. 1: from past to present.
AB  - In the present era of adhesive dentistry light-curing units are essential pieces
      of surgery equipment for everyday practice. The success and longevity of light
      activated resin sealants, photo-cured restorations and orthodontic treatments are
      related to the efficacy of the light-curing process. Energy efficient blue LED
      lights are rapidly replacing their halogen lamp predecessors as the standard
      light source. Manufacturers are producing materials with different initiators and
      not all of these materials can be properly polymerized with blue LED lights.

PMID- 22408887
TI  - A current update on osteonecrosis of the jaw and bisphosphonates.
AB  - Bisphosphonates are effective drugs used to treat important medical conditions
      affecting the skeleton, such as malignancy and osteoporosis. Bisphosphonate
      associated osteonecrosis of the jaw (BONJ) is a rare but painful condition that
      can affect quality of life. Healthcare professionals need to be aware of this
      potential side-effect of bisphosphonates, as well as ways to minimize its
      occurrence.

PMID- 22408888
TI  - The current status of 3D imaging in dental practice.
AB  - This article aims to describe the current status of 3-dimensional (3D) imaging in
      dental practice. Advances in this field have made 3D imaging far more accessible
      in all dental fields. This paper describes methods of imaging dental hard and
      soft tissues and their clinical uses. In addition, the potential advantages and
      disadvantages of various systems are discussed, as well as expected future
      developments.

PMID- 22408889
TI  - A composite approach to the management of worn maxillary first molar teeth.
AB  - A lady with extrinsic acid erosion was referred to the restorative department at
      Bristol Dental Hospital by her General Dental Practitioner (GDP) for restoration
      of worn maxillary first molar teeth. These teeth were both causing symptoms of
      dentinal sensitivity and two attempts had been made to restore them with
      composite by her GDP. The restorations failed because there was insufficient
      space to bond the composite in place, which was due to dento-alveolar
      compensation of the first molars into the space created by the wear. Following
      relevant preventive advice, the maxillary first molar teeth were restored with
      'high' direct composite resin, which allowed for adequate strength in bulk for
      retention while acting as fixed intrusion devices. These cured the patient's
      sensitivity and within four months her occlusion compensated for the composites
      and had re-established.

PMID- 22408890
TI  - Indications for fissure sealants and their role in children and adolescents.
AB  - The aim of this article is to summarize and interpret present knowledge and
      evidence on the effect of fissure sealing permanent first and second molars in
      children and adolescents with two commonly used materials: resin sealants and
      glass ionomer sealants. Also, to identify important gaps in our knowledge. The
      results show that the conclusions from systematic reviews differ in several
      aspects, and that important knowledge gaps still exist, such as the costs and
      benefits of sealing low- versus high-risk populations. The effect of sealing
      noncavitated caries lesions is uncertain and possible differences in effect
      between resin sealants and the high viscosity glass ionomers need to be
      investigated.

PMID- 22408891
TI  - Incidental finding of sialolithiasis in the sublingual gland: a diagnostic
      dilemma.
AB  - This case describes a 35-year-old female who presented with an incidental finding
      of sublingual gland sialolithiasis. The clinical presentation, investigations and
      management as well as the pathology are described. This case highlights the
      diagnostic dilemma in determining the anatomical position of sialoliths on
      radiographs.

PMID- 22408892
TI  - The use of zirconium, single-retainer, resin-bonded bridges in adolescents.
AB  - This paper presents a series of case reports which demonstrate the replacement of
      the causes of tooth loss which primarily affect children by the use of all
      ceramic resin-bonded bridges.

PMID- 22408893
TI  - Multiple radio-opacities in an OPG: a case report of cavernous haemangioma of
      temporalis muscle with multiple phleboliths.
AB  - Intramuscular haemangiomas of the head and neck region are rare. They may present
      as an incidental finding, a mass or swelling, pain, tenderness, limitation of
      movement or cosmetic deformity. Treatment depends on the clinical signs and
      symptoms. Because of the apparent rarity of this lesion, we report a case of an
      incidental finding of multiple radio-opacities in a dental panoramic tomograph
      that was diagnosed as cavernous haemangioma in temporalis muscle with multiple
      phleboliths.

PMID- 22408895
TI  - Caries and the older patient.

PMID- 22408896
TI  - Dilaceration: an endodontic challenge.

PMID- 22408897
TI  - Oral cancer: comprehending the condition, causes, controversies, control and
      consequences. 12. Radiotherapy and chemotherapy.

PMID- 22408898
TI  - Technique tips--a simple technique to correct tooth rotation.

PMID- 22408899
TI  - Physical signs for the general dental practitioner. Case 90. Purpuric rash.

PMID- 22408900
TI  - Biosynthesis of gold nanoparticles.
AB  - Synthesis of nanoparticles with interesting physico-chemical properties using
      efficient as well as eco-friendly technology is one of the main objectives of
      nanotechnology. Biological systems have been reported to synthesize inorganic
      materials under certain circumstances. Exploiting the biosynthetic potential of
      different organisms, nanoparticles of varying morphologies and sizes have been
      synthesized. Among the nanomaterials, gold has received considerable attention
      owing to its varied applications in the fields of nano-medicine, catalysis,
      electronics, and optics. This review gives an account on the biosynthesis of gold
      nanoparticles from microorganisms, plants, and other biological sources, with
      particular emphasis on the probable mechanisms leading to the formation of gold
      nanoparticles and the extent of control over nanoparticle properties that has
      been achieved so far in the biosynthetic protocols. It has been speculated that
      enzymes and/or proteins secreted by the organisms are involved in the bio
      reduction and stabilization of the nanoparticles. The biosynthetic procedures
      could compete with existing solvent-based chemical synthetic procedures in order
      to achieve stable and monodisperse gold nanoparticles in large scale.

PMID- 22408901
TI  - Synthesis and characterization of Fe3O4@SiO2 core-shell magnetic microspheres for
      extraction of genomic DNA from human whole blood.
AB  - An improved procedure was described for preparation of monodisperse Fe3O4@SiO2
      core-shell magnetic microspheres via solvothermal method followed by a modified
      Stober process. The magnetic composite microspheres were characterized with TEM,
      SEM, FTIR and VSM. Genomic DNA was then extracted from human whole blood using
      the as synthesized magnetic microspheres on the Eppendorf epMotion5075
      workstation. The quality of eluted DNA was evaluated by PCR. The method was very
      expeditious without using toxic compounds such as phenol or chloroform and can be
      used for further molecular biology experiments.

PMID- 22408902
TI  - Aqueous synthesis of Au:CdTe nanocrystals for noninvasive fluorescence imaging in
      living cells.
AB  - The gold-doped cadmium telluride (Au:CdTe) nanocrystals were synthesized by
      aqueous solution route using L-glutathione and L-cysteine as stabilizers. As
      prepared Au:CdTe nanocrystals have good monodispersity and a zinc-blende
      structure. Compared with undoped CdTe nanocrystals, the Au:CdTe nanocrystals
      exhibited improved photostability, higher cellular affinity, and lower
      cytotoxicity. The Au:CdTe nanocrystals were used as probes for long-term
      noninvasive fluorescence imaging in living cells (The human lung epithelial
      carcinoma A549 cells). They could be endocytic uptaken by A549 cells and stably
      labeled the cytoplasm for over a week. By transmission electron microscopy (TEM)
      analysis, the Au:CdTe NCs could be observed in vesicles after being uptaken by
      A549 cells. Doping semiconductor nanocrystals with gold has the potential to
      engineer the photostability and biocompatibility for extensive biomedical
      applications. This work developed a facile aqueous solution route to synthesize
      gold-doped semiconductor nanocrystals and may assist in the design of doped
      nanobiomaterials.

PMID- 22408903
TI  - Effects of nanomaterials on luciferase with significant protection and increased
      enzyme activity observed for zinc oxide nanomaterials.
AB  - This principle goal of this research was to examine the effects of various
      nanomaterials on the activity and behavior of the firefly enzyme luciferase.
      Nanomaterials have been found to stabilize, and in some instances, shown to
      increase the activity of enzymes. In this study gold, manganese oxide (MnO), and
      zinc oxide (ZnO) nanomaterials were utilized in order to test their effects on
      enzyme activity. Luciferase was used because its activity is easy to analyze, as
      it typically produces a large amount of bioluminescence easily detected by a
      Microtiter plate reader. Following incubation with the various nanomaterials,
      luciferase was subjected to degradation by several protein denaturing agents,
      such as heat, SDS, urea, ethanol, protease, hydrogen peroxide, and pH changes.
      Results indicated that luciferase activity is indeed affected when combined with
      nanomaterials, accompanied by both increases and decreases in enzyme activity
      depending on the type of nanomaterial and denaturing agent used. In most of the
      experiments, when incubated with ZnO nanomaterials, luciferase depicted
      significant increases in activity and bioluminescence. Additional experiments, in
      which human A375 cells were treated with luciferase-nanomaterial mixtures, also
      depicted increased enzyme activity and bioluminescence for luciferase incubated
      with ZnO nanomaterials. Ultimately, our findings indicated that when luciferase
      was subjected to multiple types of denaturation, zinc oxide nanomaterials
      dramatically preserved and increased enzyme activity and bioluminescence.

PMID- 22408904
TI  - Disposable biosensor based on Au nanoparticles-modified CdS nanorod arrays for
      detection cytochrome c.
AB  - A novel disposable biosensor is developed based on gold nanoparticles modified
      CdS nanorod arrays. The ordered CdS nanorod arrays firstly have been synthesized
      by a simple hydrothermal method. Then, the CdS nanorod arrays are modified by
      gold nanoparticles, which are directly fabricated into an electrode for detection
      of cytochrome c (Cyc) in solution without any pretreatment. The modified CdS
      nanorod arrays biosensor with the immense surface area and high electrical
      conductivity shows a good sensitivity and linear range. This method may be used
      to construct other electrochemical biosensors using aligned nanorod/nanowire
      films.

PMID- 22408905
TI  - Thermal decomposition behavior of amino groups modified bimodal mesoporous
      silicas as aspirin carrier.
AB  - Two kinds of amino groups were employed to functionalize bimodal mesoporous
      silicas and related drug carriers were prepared. The characterization results of
      XRD, N2 adsorption and desorption, FT-IR and TG all confirmed the structural
      integrity of the bimodal mesopore architecture after introduction treatment of
      functional groups and the successful adsorption of aspirin. In order to
      investigate the interaction among the mesoporous structure, the functional groups
      grafted onto the mesoporous surface and the existential microenvironment of the
      drug molecules inside the mesoporous channels, the thermal decomposition
      behaviors of amino groups modified and aspirin loaded carriers were studied based
      on the thermogravimetric analysis in details. According to the thermogravimetry
      and derivative thermogravimetry results, the apparent activation energies E(a) of
      thermal decomposition for all related samples have been evaluated by Kissinger
      and Flynn-Wall-Ozawa methods. Meanwhile, their thermal decomposition mechanisms
      have been suggested by using Coats and Redfern methods. All these featured
      consequence could provide a deeper understanding for large loading capacity and
      controlled release of drug-carriers in the pharmaceutical application.

PMID- 22408906
TI  - Thermal analysis in the rat glioma model during directly multipoint injection
      hyperthermia incorporating magnetic nanoparticles.
AB  - Hyperthermia incorporating magnetic nanoparticles (MNPs) is a hopeful therapy to
      cancers and steps into clinical tests at present. However, the clinical plan of
      MNPs deposition in tumors, especially applied for directly multipoint injection
      hyperthermia (DMIH), and the information of temperature rise in tumors by DMIH is
      lack of studied. In this paper, we mainly discussed thermal distributions induced
      by MNPs in the rat brain tumors during DMIH. Due to limited experimental
      measurement for detecting thermal dose of tumors, and in order to acquire
      optimized results of temperature distributions clinically needed, we designed the
      thermal model in which three types of MNPs injection for hyperthermia treatments
      were simulated. The simulated results showed that MNPs injection plan played an
      important role in determining thermal distribution, as well as the overall dose
      of MNPs injected. We found that as injected points enhanced, the difference of
      temperature in the whole tumor volume decreased. Moreover, from temperature
      detecting data by Fiber Optic Temperature Sensors (FOTSs) in glioma bearing rats
      during MNPs hyperthermia, we found the temperature errors by FOTSs reduced as the
      number of points injected enhanced. Finally, the results showed that the
      simulations are preferable and the optimized plans of the numbers and spatial
      positions of MNPs points injected are essential during direct injection
      hyperthermia.

PMID- 22408907
TI  - Improved light extraction from large-area vertical light-emitting diodes with
      deep hole-patterns using nanosphere lithography.
AB  - The authors report on an improved light extraction method from large-area
      vertical light emitting diodes (VLEDs) with deep hole-patterns fabricated using
      nanosphere lithography. In order to produce the ordered deep-hole patterns on the
      n-type GaN surface, a 150 nm thick Ni dot mask formed via a lift-off process of
      the Ni coated onto a 500 nm diameter polystylene bead array was employed to
      enable deep etching. Three VLEDs-one as a reference with no patterns, and two
      with periodic 360 nm diameter hole patterns, one with 1.0 microm and the other
      with 1.5 microm depths on the n-type GaN surface, were prepared for comparison.
      The light output power measured for the VLEDs with the hole-patterns increased by
      4.13 and 4.86 times, respectively, as compared to the reference VLED. These
      enhancements are attributed to the multiple scatterings of the light from the
      sidewall of the hole-patterns and to the increased surface area to which the
      light can approach. The higher light output power obtained for the VLEDs with the
      deep hole patterns might be due to a photon reabsorption reduction within the n
      GaN layer.

PMID- 22408908
TI  - Dispersion characteristics of TiO2 particles coated with the SiO2 nano-film by
      atomic layer deposition.
AB  - Deposition of SiO2 nanofilm on TiO2 particles using atomic layer deposition
      method is reported. The SiO2 film was prepared at the room temperature using the
      chemicals Si(OC2H5)4, C2H5N and H2O as precursor, catalyst and reactant gas,
      respectively. The thickness, composition and uniformity of the SiO2 coating on
      TiO2 surface were characterized by FESEM, HRTEM, EDS and XPS measurements. In
      HRTEM analysis, the growth rate was about 0.33 angstroms/cycle. EDS and XPS
      analysis showed the surface composition of TiO2 nanoparticles was silicon oxide.
      Zeta potential, particle size distribution and sedimentation test results
      indicated that dispersibility of coated nanoparticles was higher than that of
      uncoated nanoparticles because of the electrostatic repulsion between the SiO2
      coated layers on the surface of TiO2 nanoparticles. These results suggested that
      the SiO2 coating could modify the surface characteristics of the TiO2
      nanoparticles and improve the dispersibility of the TiO2 primary nanoparticles.

PMID- 22408909
TI  - Chemical functionalization of diatom silica microparticles for adsorption of gold
      (III) ions.
AB  - Diatom silica microparticles from natural diatomaceous earth (DE) silica have
      been functionalized with 3-mercaptopropyltrimethoxysilane (MPTMS) and their
      application for adsorption of gold (III) ions from aqueous solutions is
      demonstrated. Fourier transform infrared spectroscopy (FTIR) and X-ray
      Photoelectron spectroscopy (XPS) analyses of the MPTMS modified diatom
      microparticles revealed that the silane layer with functional group (-SH) was
      successfully introduced to the diatom surface. The adsorption study of Au(III)
      ions using MPTMS-DE indicated that the process depends on initial gold (III)
      concentration and pH showing maximum adsorption capacity at pH = 3. The Au(III)
      adsorption kinetics results showed that the adsorption was very fast and followed
      a pseudo-second-order reaction model. The Langmuir model was used to provide a
      sound mechanistic basis for the theoretical of the adsorption equilibrium data.
      Gold recovery from MPTMS-DE structures was also investigated by using acidified
      thiourea solution and found to be high (> 95%). These results show that
      chemically modified DE microparticles can be used as a new, cost effective and
      environmentally benign adsorbent suitable for adsorption of gold metal ions from
      aqueous solutions.

PMID- 22408910
TI  - Recent development of LiNi1/3Co1/3Mn1/3O2 as cathode material of lithium ion
      battery.
AB  - Layered LiNi1/3Co1/3Mn1/3O2, owing to its excellent electrochemical properties,
      has been used as cathode material for lithium-ion batteries, especially for
      hybrid electric vehicles. It has many merits such as high capacity, long cycle
      life, low cost and little harm to environment. Therefore, LiNi1/3Co1/3Mn1/3O2 has
      become a great concern by scholars on energy and material fields. However, the
      electronic conductivity and the charge-discharge capacity at high current should
      be enhanced before any materials modifications. Here, this paper summarizes the
      main synthetic technologies of LiNi1/3Co1/3Mn1/3O2 in recent years, including
      synthesis methods, doping, surface coating modification, and the future
      development trends discussed.

PMID- 22408911
TI  - Preparation of spinous ZrO2 microspheres with tunable shell and chamber structure
      by controlling pollen as a nanoparticles reactor.
AB  - Spinous hollow and core-shell microspheres constructed from ZrO2 nanoparticles
      and keeping the complex morphology of pollens were prepared by bio-template
      route. Compared with other bio-templates synthesis, the superiority of our
      synthesis is that the growth of nanoparticles can be controlled in particular
      space of template. The theory of pollen as a reactor and a possible formation
      mechanism were proposed which could explain the tunable structure: under a mild
      condition, the pollen wall will be controlled as a nanoparticles bio-reactor to
      form the hollow structure; when under a strenuous condition, pollen wall and
      pollen interior will act as a whole bio-reactor, and the core-shell structure
      could be obtained. At the same time, the shell thickness can be controlled
      through etching pollen wall by different concentrations HCl. These microspheres
      can be used as photocatalyst due to their unique structure. This work provides a
      novel pathway to the synthesis of hollow nanostructure spheres with complicated
      structure and morphology.

PMID- 22408912
TI  - Study on gelatin-silver nanoparticle composite towards the development of bio
      based antimicrobial film.
AB  - Nano-scale silver particle stabilized by gelatin protein was prepared through the
      reduction of aqueous silver nitrate solution by sodium borohydride. Gelatin
      concentration was varied against a fixed concentration of silver nitrate to
      optimize the gelatin to metal ratio. Gelatin-protected Ag-nanoparticle was
      characterized by UV-VIS spectroscopy and transmission electron microscopy (TEM).
      All the samples exhibited similar yellow color with a characteristic plasmonic
      band of silver nanoparticles at 412 nm. TEM micrographs also showed the presence
      of nanoscale silver particles of approximately 3.9 nm. Since silver has strong
      bactericidal properties and at the same time relatively less toxic to human cell,
      silver in various forms is ideally suited for a wide range of applications in
      consumer, industrial and medical products The antimicrobial properties of gelatin
      silver nanocomposites were tested by 'cup-plate zone of inhibition' method. The
      nanocomposites exhibited significant antibacterial and antifungal activity.

PMID- 22408913
TI  - Growth of aligned ZnO nanorod arrays from an aqueous solution: effect of
      additives and substrates.
AB  - We report a simple, versatile, low cost fabrication technique for synthesizing
      nanorod arrays whose architecture is suited for many applications spanning the
      nanometer to micrometer range. Specifically, we have covered the range of nanorod
      diameter from 50 to 1200 nm. From a detailed study of the growth parameters
      involved in the synthesis of the ZnO nanorod arrays from an aqueous solution, we
      report, in particular, the effects of varying the capping agent, substrate and
      substrate-seeding. We find that seeding the substrate and selecting the
      appropriate capping agent play the most crucial roles in the alignment of nanorod
      arrays. Our study on the use of different precursor materials and varied
      substrates for the growth of ZnO nanorod arrays should lead to an enhanced
      understanding of the controllable growth of ZnO crystals and nanostructures.

PMID- 22408914
TI  - Preparation of guanidine group functionalized magnetic nanoparticles and the
      application in preconcentration and separation of acidic protein.
AB  - Guanidine group (Gnd) functionalized magnetic nanoparticles (Fe3O4@SiO2@NH2-Gnd)
      were synthesized and characterized in this work for the first time. The
      characterization of Fe3O4@SiO2@ NH2-Gnd nanoparticles was demonstrated by
      transmission electron microscopy, X-ray diffraction, Fourier transform infrared
      spectra, vibration sample magnetometer, and zeta potential analyzer. The novel
      multifunctional nanoparticles were served as a solid-phase extraction sorbent for
      easy isolation and preconcentration of acidic protein from aqueous solution only
      using a magnet. Bovine serum albumin (BSA) was selected as a model protein and
      the main experimental parameters influencing the adsorption and desorption
      efficiency were investigated and optimized. Under the optimum conditions, the
      particles reached saturated adsorption within 20 min and exhibited significant
      specific recognition for the acidic proteins. Fifteen fold enrichment efficiency
      was achieved and the detection limits was 45 ng x mL(-1) for BSA by capillary
      electrophoresis (CE). The practical application of the novel nanoparticles as a
      sorbent for the isolation and preconcentration of acidic proteins from basic
      proteins was demonstrated by effective separation and enrichment of bovine serum
      albumin from lysozyme and cytochrome C mixture, which was assayed by CE.

PMID- 22408915
TI  - New method for synthesis of Pt nanoparticles embedded in a carbon matrix.
AB  - Platinum (Pt) nanoparticles embedded in a carbon matrix were synthesized for the
      first time in benzene by an electric plasma discharge generated in the cavitation
      field of benzene due to an ultrasonic horn. Transmission electron microscopy
      (TEM) and X-ray diffraction (XRD) were used to study the particle size, structure
      and morphology of the synthesized nanoparticles. The Pt nanoparticles have FCC
      bulk Pt crystal structure. On the average Pt nanoparticle diameter ranged from 8
      nm to 40 nm when synthesized at 4.1 kV and from 5 nm to 25 nm when synthesized at
      3.4 kV. X-ray photoelectron Spectroscopy (XPS) and Energy dispersive X-ray
      Spectroscopy (EDX) were used to study the chemical composition of the synthesized
      nanoparticles. A cost effective new method for carbon supported Pt nanoparticles
      will be of potential interest in fuel cell and catalysis applications.

PMID- 22408916
TI  - Nonlocal continuum model and molecular dynamics for free vibration of single
      walled carbon nanotubes.
AB  - Free transverse, longitudinal and torsional vibrations of single-walled carbon
      nanotubes (SWCNTs) are investigated through nonlocal beam model, nonlocal rod
      model and verified by molecular dynamics (MD) simulations. The nonlocal
      Timoshenko beam model offers a better prediction of the fundamental frequencies
      of shorter SWCNTs, such as a (5, 5) SWCNT shorter than 3.5 nm, than local beam
      models. The nonlocal rod model is employed to study the longitudinal and
      torsional vibrations of SWCNT and found to enable a good prediction of the MD
      results for shorter SWCNTs. Nonlocal and local continuum models provide a good
      agreement with MD results for relatively longer SWCNTs, such as (5, 5) SWCNTs
      longer than 3.5 nm. The scale parameter in nonlocal beam and rod models is
      estimated by calibrations from MD results.

PMID- 22408917
TI  - Molecular interaction and properties of poly(ether ether ketone)/liquid
      crystalline polymer blends incorporated with functionalized carbon nanotubes.
AB  - Multi-walled carbon nanotubes (MWCNTs) were functionalized with a carboxyl group
      (-COOH) to achieve better interfacial adhesions with both phases of the
      poly(ether ether ketone) (PEEK) and liquid crystalline polymer (LCP) in their
      blend. These strong interfacial interactions among the functionalized MWCNTs,
      PEEK and LCP improved the mechanical properties of the polymer blend. Three
      different weight percentages (0.6%, 1.2% and 1.8%) of acid modified CNTs were
      used with PEEK-LCP blend, for the preparation of nanocomposites. In PEEK-LCP
      blend, the ratio of PEEK and LCP was maintained as 10:6 respectively. The tensile
      strength and modulus of the composites were improved by 51% and 73% respectively
      with the incorporation of only 1.2% of MWCNT-COOH as compared to the unfilled
      PEEK/LCP blend. Moreover, careful studies of the molecular interaction,
      morphological, dynamic mechanical and thermal properties confirmed that a better
      miscibility between PEEK and LCP had been constituted in the presence of MWCNT
      COOH. Therefore, it was found that the functionalized MWCNTs not only played the
      traditional role as reinforcing filler, but also performed a novel role as a
      compatibilizer for the PEEK/LCP blends.

PMID- 22408918
TI  - Fabrication and characterization of twin poly-Si thin film transistors EEPROM
      with a nitride charge trapping layer.
AB  - This study investigates the characteristics of the planar twin poly-Si thin film
      transistor (TFT) EEPROM that utilizes a nitride (Si3N4) charge trapping layer. A
      comparison is made of two devices with different gate dielectrics, one a 16 nm
      thick oxide (SiO2) layer for O-structure and the other 5 nm/10 nm-thick
      oxide/nitride layers for O/N-structure. Incorporating a nitride charge trapping
      layer and reducing the tunneling oxide thickness enable the O/N-structure EEPROM
      to enhance the program/erase (P/E) efficiency. Additionally, EEPROM formed with
      the tri-gate nanowires (NWs) structure can further enhance P/E efficiency and a
      large memory window because of its high electric field across the tunneling
      oxide. Reliability results indicated that, since the nitride layer contains
      discrete traps, the memory window can be maintained 2.2 V after 10(4) P/E cycles.
      For retention, the memory window can be maintained 1.9 V, and 30% charge loss for
      ten years of data storage. This investigation indicates that its possibility in
      future system-on-panel (SOP) of thin-film transistor liquid crystal display
      (TFTLCD) and 3-D stacked high-density Flash memory applications.

PMID- 22408919
TI  - Study of carbon nanotube field effect transistors performance based on changes in
      gate parameters.
AB  - Carbon nanotubes are known as an interesting material to be used in the next
      generations of electronic technology, especially at nano regime. Nowadays, carbon
      nanotube field effect transistor or CNTFET is one of the promising devices for
      future electronic applications. A CNTFET which uses carbon nanotube as channel or
      source/drain region is the most promising candidate for replacing the current
      silicon transistor technology. The study of modern manufacturing approach and
      impact of device parameters on its performance is one of the important research
      fields in nanoelectronics. In this paper we study some aspects of changes in gate
      parameters at different channel diameters. This paper shows that for small values
      of diameter, increasing the dielectric constant of gate insulator doesn't help to
      improve the performance as value of dielectric constant of gate insulator reaches
      a certain amount. Also, increasing the oxide thickness of gate insulator doesn't
      always decrease transistor performance. For high diameter values, increasing the
      thickness up to a certain value improves the transistor performance.

PMID- 22408920
TI  - Impact of random dopant fluctuation effect on surrounding gate MOSFETs: from
      atomic level simulation to circuit performance evaluation.
AB  - This paper investigates the impact of random dopant fluctuation effect on
      surrounding gate MOSFET, from atomic statistical simulation of device to circuit
      performance evaluation. The doping profile is generated by an analysis of each
      lattice atom and then the threshold voltage variation is obtained by device Drift
      Diffusion simulation. Then the circuit performance evaluation is performed by
      feeding the result into a surrounding-gate MOSFET model. It is shown that a
      significant fluctuation in threshold voltage is due to the decreasing volume. The
      circuit simulation results also reveal that a surrounding gate MOSFET based 6-T
      SRAM presents a promising resistibility to noise disturbance.

PMID- 22408921
TI  - Optimal design of 3-D carbon microelectrode array for dielectrophoretic
      manipulation of nanoparticles in fluids.
AB  - Manipulation of nanoparticles using nonuniform electric fields is an area of
      growing interest for nanotechnology applications. This article presents a design
      methodology and numerical analysis of electric fields and dielectrophoretic
      forces for 3-dimensional (3-D) carbon microelectrode array, overcoming the
      limitations of previous approaches. A description of the boundary element method
      is developed to compute electric field distribution much precisely. The effects
      of electrode shape, spacing, width and height on field distribution are
      considered. The results show that the gradient magnitude produced by square
      column electrodes is most effective to realize manipulation of nanoparticles in
      fluids. As both the electrode spacing and width are reduced the field gradient
      magnitude increases exponentially. By increasing the height of electrodes, the
      electric field extends largely in the electrode locality, which is advantageous
      to improve the manipulation efficiency with high degree of precision, flexibility
      and throughput. The theoretical predictions will provide design guides for 3-D
      carbon microelectrode array towards manipulation of nanoparticles in fluids,
      which have been shown in reasonable agreement with literature experimental
      reports.

PMID- 22408922
TI  - Hydrothermal synthesis of a highly sensitive T2-weigthed MRI contrast agent: zinc
      doped superparamagnetic iron oxide nanocrystals.
AB  - A highly efficient hydrothermal strategy for the synthesis of zinc-doped
      superparamagnetic iron oxide nanocrystals (SPION:Zn) with lower toxicity and
      improved sensitivity has been demonstrated. The saturation magnetizations of as
      synthesized SPION:Zn were demonstrated to be Zn-dependent and could be tuned from
      41.88 emu/g to 79.23 emu/g by changing the amount of Zn. As-synthesized
      hydrophobic SPION:Zn could be efficiently transferred into water phase through a
      ultrasonic process with the assistance of cetyltrimethylammonium bromide (CTAB)
      surfactant. As-obtained CTAB stabilized SPION:Zn was exploited as a MR enhanced
      contrast agent, and its T2 relaxivity coefficient (r2) was found to be as high as
      342.09 mM(-1)s(-1).

PMID- 22408923
TI  - Hydrothermal synthesis and biocompatibility of hydroxyapatite nanorods.
AB  - A facile micelle precursor having cyclohexane/ethanol/cetyl trimethyl ammonium
      bromide/aqueous phase was treated hydrothermally to form nanohydroxyapatite. The
      synthesized products were characterized by means of X-ray diffraction,
      thermogravimetric analysis, transmission electron microscopy and energy
      dispersive X-ray spectroscopy. The results showed that the synthesized products
      display the crystalline structure and vibration modes of hydroxyapatite.
      Transmission electron micrograph revealed that nanohydroxyapatite exhibits
      elongated rod morphology with large aspect ratios. Nanohydroxyapatite prepared
      from a surfactant of 1.25 millimole showed good thermal stability at 1000 degrees
      C on the basis of thermogravimetric analysis. Simulated body fluid immersion test
      indicated that an apatite layer can be readily deposited on the
      nanohydroxyapatite surface demonstrating its good bio-resorbability.

PMID- 22408924
TI  - Novel all-optical logic gate using an add/drop filter and intensity switch.
AB  - A novel design of all-optical logic device is proposed. An all-optical logic
      device system composes of an optical intensity switch and add/drop filter. The
      intensity switch is formed to switch signal by using the relationship between
      refraction angle and signal intensity. In operation, two input signals are
      coupled into one with some coupling loss and attenuation, in which the
      combination of add/drop with intensity switch produces the optical logic gate.
      The advantage is that the proposed device can operate the high speed logic
      function. Moreover, it uses low power consumption. Furthermore, by using the
      extremely small component, this design can be put into a single chip. Finally, we
      have successfully produced the all-optical logic gate that can generate the
      accurate AND and NOT operation results.

PMID- 22408925
TI  - An electronic nose for amine detection based on polymer/SWNT-COOH nanocomposite.
AB  - An electronic nose (e-nose) system based on polymer/carboxylic-functionalized
      single-walled carbon nanotubes (SWNT-COOH) was developed for sensing various
      volatile amines. The SWNT-COOH dispersed in the matrix of different polymers;
      namely, polyvinyl chloride (PVC), cumene terminated polystyrene-co-maleic
      anhydride (cumene-PSMA), poly(styrenecomaleic acid) partial isobutyl/methyl mixed
      ester (PSE), and polyvinylpyrrolidon (PVP), were deposited on interdigitated gold
      electrodes to make the gas sensors. The response of these sensors to volatile
      amines was studied by both static and dynamic flow measurements. It was found
      that all sensors exhibited behaviors corresponding to Plateau-Bretano-Stevens law
      (R2 = 0.81 to 0.99) as the response to volatile amines. Real-world application
      was demonstrated by applying this e-nose to monitor the odor of sun-dried
      snakeskin gourami that was pre-processed by salting-preservation. This electronic
      nose can discriminate sun-dried fish odors with different stored days using a
      simple pattern recognition based on the principal component analysis (PCA).

PMID- 22408926
TI  - Microdiaphragm resonating biosensors in higher frequency modes.
AB  - Influences of different vibration modes of microdiaphragm resonating biosensors
      on their detecting capability are investigated in this paper. In order to study
      the mass sensing capability of the sensor, gold layers with different thicknesses
      are deposited on the sensor's surface. The frequency shift due to this mass
      deposition in different frequency modes is measured. An increase in the
      sensitivity and the quality factor (Q-factor) is found with the increase in the
      vibration mode number of the sensor. The experimental results demonstrate that
      the mass sensitivity and quality factor of the device are 4.08 Hz/ng and 241.80
      at the ninth mode. These are 2.76 and 10.26 times higher than the mass
      sensitivity and the Q-factor of the device at the first mode. The observations
      lead to this conclusion that the sensitivity of microdiaphragm resonating
      biosensors can be increased by working in higher modes without changing their
      physical parameters.

PMID- 22408927
TI  - Electronic properties of GaP nanowires of different shapes.
AB  - The electronic properties of very thin gallium phosphide nanowires of different
      shapes were studied by ab-initio method using the generalized gradient
      approximation. We consider four different shapes of nanowires viz. linear wire,
      zigzag wire, square wire and hexagonal wire. The geometry optimization and the
      stability of all nanowires were investigated. We explore the minimum energy
      configuration for all the structures. The present study reveals that all of the
      wires are stable but four atom square wires have greater stability in comparison
      to other structures. The analysis of density of states and band structure of
      optimized nanowires predicts that nanowires made from bulk GaP can be either
      metallic, semi-metallic, semiconducting or insulating depending upon the
      geometrical shape of the wire.

PMID- 22408928
TI  - Program and read scaling trade-offs in phase change memories.
AB  - This paper investigates the scaling perspectives of Phase Change Memory
      technology by analyzing the effects of geometrical dimensions reduction and the
      read voltage scaling on program and read operations. To this end, we derive
      analytical expressions which allow us to estimate the dependence of the RESET and
      read current on key geometrical parameters of the memory cell, such as heater
      size and chalcogenide layer thickness.

PMID- 22408929
TI  - A quantum mechanical transport approach to simulation of quadruple gate silicon
      nanowire transistor.
AB  - In this paper we have used quantum mechanical transport approach to analyse
      electrical characteristics of silicon nanowire transistor and have compared the
      results with those obtained using semi classical Boltzmann transport model. The
      analyse employs a three dimensional simulation of Silicon nanowire transistor
      based on self consistent solution of Poisson, Schrodinger equations. Quantum
      mechanical transport model uses the non equilibrium Green's function (NEGF) while
      the semi classic model doesn't account for tunneling current. The results have
      shown that Quantum tunneling is significant in inversion condition especially
      when the channel length is short. For the long devices quantum modeling and semi
      classical model produce the same result, and tunneling is negligible.

PMID- 22408930
TI  - A unified drain current model for nanoscale double-gate and surrounding-gate
      MOSFETs incorporating velocity saturation.
AB  - A unified drain current model for undoped or lightly doped symmetric double-gate
      and surrounding-gate MOSFETs incorporating velocity saturation effect is proposed
      in this paper. The unified charge-based core model for undoped or lightly doped
      double-gate and surrounding-gate MOSFETs is presented first based on the
      previously published separate models. Caughey-Thomas engineering mobility model
      with its exponent factor n = 2 is then integrated self-consistently into the
      unified drain current model development of the two device structures. Extensive
      two dimensional and three dimensional device simulations are performed to
      validate the proposed model. Good agreements of the output and transfer
      characteristics between the unified model and the numerical simulations are
      obtained for both the double-gate and surrounding-gate MOSFETs. Symmetry property
      of the proposed unified current model is obtained with the exponent factor n = 2
      in Cauhey-Thomas Model.

PMID- 22408931
TI  - Analysis and modeling of nano-crystalline silicon TFTs on flexible substrate with
      mechanical strain.
AB  - The gap state density of nano-crystalline silicon active layers on a flexible
      substrate was redistributed with mechanical bending. The weak or broken bonds may
      contribute to the redistribution of trap states. During mechanical strain, the
      deep states redistributed in a Gaussian distribution, and are dissimilar to
      ordinary acceptor-like deep states, which manifest with exponential
      distributions. We conclude that the gap state density with TCAD modeling under
      mechanical strain is the fundamental reliability issue for the development of
      flexible electronics.

PMID- 22408932
TI  - Electron eigenstates in quantum dots revealed by temperature derivative
      capacitance spectroscopy.
AB  - A novel method is presented for detecting confined energy states in quantum dots
      embedded in a junction space charge region, where the reverse bias is used to
      discharge the initially occupied energy levels. By determining the temperature
      derivative of junction capacitance as a function of bias voltage and temperature,
      spectra are obtained with peaks revealing the existence of electron states in
      InGaAs/GaAs quantum dots structure grown by molecular beam epitaxy. The method is
      compared with admittance based techniques and theory used earlier for
      interpretation of experimental data.

PMID- 22408933
TI  - The influences of rapid-thermal annealing on the characteristics of
      Sr0.6Ba0.4Nb2O6 thin film.
AB  - The Sr0.6Ba0.4Nb2O6 (SBN) thin films were successfully prepared on Pt/Ti/Si and
      SiO2/Si/Al substrates and crystallized subsequently using rapid thermal annealing
      (RTA) process in ambient atmosphere for 1 min. The surface morphologies and
      thicknesses of as-deposited and annealed SBN thin films were characterized by
      field emission scanning electron microscopy, and the thickness was about 246 nm.
      As compared with the as-deposited SBN thin films, the RTA-treated process had
      improved the crystalline structures and also had large influence on the
      crystalline orientation. When the annealing temperatures increased from 700
      degrees C to 900 degrees C, the diffraction intensities of (410) and (001) peaks
      apparently increased. Annealed at 900 degrees C, the (001) peak had the maximum
      texture coefficient and SBN thin films showed a highly c-axis (001) orientation.
      The influences of different RTA-treated temperatures on the polarization-applied
      electric field (P-E) curves and the capacitance-voltage (C-V) curves were also
      investigated.

PMID- 22408934
TI  - Temperature control of microheaters for localized carbon nanotube synthesis.
AB  - The temperatures of microheater devices for the localized growth of carbon
      nanotubes (CNTs) were brought under control to a great extent by providing the
      appropriate electric load (direct current or voltage) to the microheater circuit.
      The electrical-thermal coupled field simulations show that high temperatures only
      appear in very local areas under certain electric load. The infrared image of the
      produced microheater device agrees well with the simulation results. By applying
      the selected current to the fabricated microheater device and providing the mixed
      reaction gases, long, dense, and vertically well aligned CNT bundles were
      successfully grown very locally on the substrate. The control of temperatures
      paves the way to the localized growth of CNTs with good compatibility with CMOS
      process, and thus facilitating the direct integration of CNTs into future
      micro/nano electronics as interconnects. What's more, the method will also excite
      more in depth investigations on the applications of microheaters in many other
      fields.

PMID- 22408935
TI  - Cross-section control of stacked nanowires formed by Bosch process and oxidation.
AB  - The cross-sectional shape of the stacked silicon nanowires (SiNWs) formed by the
      Bosch process and stress-limited oxidation is studied in this paper. Under the
      condition of high temperature oxidation, the resulting nanowires highly resemble
      the initial shapes resulting by the Bosch process. The effects of etching and
      passivation in the Bosch process are modeled to provide a guideline to control
      the cross-section of the stacked nanowires.

PMID- 22408936
TI  - Magnetic and optical properties of Mn doped ZnO nanocrystalline films.
AB  - We have investigated the properties of Mn-doped ZnO nanocrystalline film growing
      on zinc foil by the hydrothermal method. X-ray photoelectron spectroscopy shows
      that the manganese ions exist as Mn2+ in the film. From UV-vis spectra, we
      observe a red shift in wavelength of absorption and greater reflectivity due to
      the Mn ion incorporation in ZnO lattices. The photoluminescence spectrum of the
      Mn-doped ZnO film shows two strong new blue peaks centered at 424 nm and 443 nm,
      besides the UV emission peak owing to the band gap of ZnO semiconductor. The
      magnetic property of the Mn-doped ZnO exhibits a room temperature ferromagnetic
      characteristic with a saturation magnetization (Ms) of 0.3902 x 10(-3) emu/cm3
      and a coercive field of 47 Oe. We suggest that the blue emission of the Mn-doped
      ZnO film corresponds to the electron transition from the level of interstitial Zn
      and Mn to the valence band. The defects brought about by Mn ion incorporation are
      the main cause of the room temperature ferromagnetic property.

PMID- 22408937
TI  - Mechanism behind the formation of self-assembled nano-sized clusters in diamond
      like carbon nanocomposite.
AB  - Many studies have shown that Diamond-like carbon (DLC) films with diversified
      material properties are obtainable through doping process but the presence of the
      dopants were reported to form independent nanoclusters within the carbon matrix.
      Using combined analysis from theoretical estimations (Saha's equation and
      coefficient of absorption, alpha(p)), Transport of Ions In Matter (TRIM)
      simulation and experimental results, this work examined the mechanism behind the
      formation of self-assembled nanoclusters in DLC nanocomposite. We showed that the
      presence of metal dopants increased the heat dissipation on DLC, which allowed
      the energetic metal species to diffuse and enhance the formation of nanoclusters
      that increased the surface roughness of the films. In addition, TRIM and X-ray
      Photoelectron Spectroscopy (XPS) hinted the presence of energetic species may
      force the carbon ions to react with the interface to form silicon carbide bonds,
      which may be a more dominant factor compared to internal stress reduction in
      improving the adhesion strength of DLC.

PMID- 22408938
TI  - Tunable magnetic resonance in double layered metallic structures.
AB  - Double layered metallic gratings have been investigated both theoretically and
      experimentally. The authors have reported that tunable magnetic resonance (MR)
      can be achieved by modulating the vertical chirped width dh which could be
      controlled conveniently in the common electron and/or ion beam microfabrications.
      The linear relationship between MR wavelength and dh has been reported. By
      introducing the difference of electric and magnetic penetration depth, an
      analytic formula deduced from a modified LC model has shown good agreement with
      the simulation results, and an effective width for trapezoidal sandwiched
      microstructures has been presented. Our results may provide an alternative choice
      for tunable MR and broad bandwidth of magnetic metamaterials.

PMID- 22408939
TI  - Tunable microring resonator based on dielectric-loaded surface plasmon polariton
      waveguides.
AB  - Integrated optical ring resonators are essential elemental components for
      integrated optical circuits. An ultrasmall thermo-optical microring resonator
      with two bus waveguide-configuration based on surface plasmon polariton waveguide
      is theoretically analyzed. The thermo-optical coefficient, the temperature
      dependent amplitude attenuation coefficient and the temperature distribution
      properties of the waveguide are investigated numerically by finite element
      method. The critical resonant conditions of the microring resonator are discussed
      by considering the propagation losses in the plasmonic ring cavity. The
      transmission characteristics and the tunability of the ring resonator with
      different structural parameters are investigated. The results show that the
      proposed ring resonator with a low driving power and high efficient tunability
      has potential to develop nano-scope wavelength tunable channel drop filters, low
      power optical switches, attenuators, and other high compact integrated optical
      devices.

PMID- 22408940
TI  - Characteristics of carbon nanotubes based micro-bubble generator for thermal jet
      printing.
AB  - We propose a conceptional thermal printhead with dual microbubble generators
      mounted parallel in each nozzle chamber, where multiwalled carbon nanotubes are
      adopted as heating elements with much higher energy efficiency than traditional
      approaches using noble metals or polysilicon. Tailing effect of droplet can be
      excluded by appropriate control of grouped bubble generations. Characteristics of
      the corresponding micro-fabricated microbubble generators were comprehensively
      studied before the formation of printhead. Electrical properties of the
      microheaters on glass substrate in air and performance of bubble generation
      underwater focusing on the relationships between input power, device resistance
      and bubble behavior were probed. Proof-of-concept bubble generations grouped to
      eliminate the tailing effect of droplet were performed indicating precise pattern
      with high resolution could be realized by this kind of printhead. Experimental
      results revealed guidance to the geometric design of the printhead as well as its
      fabrication margin and the electrical control of the microbubble generators.

PMID- 22408941
TI  - Influence of radial stress on the performance of gate-all-around Ge(110) NW FETs
      with HfO2 dielectric.
AB  - In this work, a simulation method from strained valence band structures to
      strained mobility calculation to consider a radial stress at the boundary of HfO2
      gate dielectric surrounding Ge(110) nanowire is developed. The simulation
      implements the radial stress to strain distribution calculation via finite
      element method and then to valence band calculation. The radial stress at the
      boundary of gate dielectric pushes the valence subbands downwards in contrast
      with lattice mismatch strain effects between Ge NW and gate dielectric. The
      impact of the radial stress on the hole effective masses and density of states of
      HfO2 gate dielectric surrounding Ge(110) nanowire are also investigated. The
      potential distribution and holes density distribution are calculated by solving
      the 2D Poisson equation and Schrodinger equation self-consistently in NW cross
      section. Hole mobility is obtained by modified Kubo-Greenwood formula. Based on
      strained valence band structures, the hole density distribution in cross
      sectional Ge(110) NW reduces with larger radial stress value. The phonon
      scattering-limited hole mobility in NW significantly increases as the radial
      stress increases.

PMID- 22408942
TI  - Comparative analysis of trap-based program/erase behaviors with different tunnel
      barriers.
AB  - In this study, we comparatively analyze the trap-based memory characteristics of
      Oxide-Nitride-Oxide (ONO) devices with different tunnel dielectrics. We
      fabricated two kinds of ONO devices-one is the conventional single tunnel oxide
      structure and the other is the bandgap engineered structure in which the
      modulated tunnel dielectric replaces the single tunnel oxide. The charge storage
      layer is 9 nm and the blocking oxide is 7 nm in both two kinds of ONO devices.
      Based on experimental results, we find that the memory speed is promoted to 2-4
      times and 10-year data retention greatly improves in the bandgap engineered
      device comparing to those in the conventional device. As a result, the bandgap
      engineered tunnel barrier device embodies both fast P/E operation speeds and
      excellent long-term data retention characteristics, hence, the bandgap engineered
      tunnel barrier is expected to conduct performance optimization for the future
      scaled SONOS flash memory.

PMID- 22408943
TI  - Facile fabrication of Si nanowire arrays for solar cell application.
AB  - Large-area Si nanowire arrays have been fabricated on phosphorus doped Si surface
      by a facile silver-catalyzed chemical etching process. The solar cell
      incorporated with Si nanowire arrays shows a power conversion efficiency of 6.69%
      with an open circuit voltage of 558 mV and a short circuit current density of
      25.13 mA/cm2 under AM 1.5 G illumination without using any extra antireflection
      layer and surface passivation technique. The high power conversion efficiency of
      Si nanowires based-solar cell is attributed to the low reflectance loss of Si
      nanowire arrays for incident sunlight. Optimization of electrical contact and
      phosphorus diffusion process will be critical to improve the performance of Si
      nanowires-based solar cell in the future.

PMID- 22408944
TI  - Decrease of the OFF state current of carbon nanotube field effect transistors via
      continuous repeated gate sweeping.
AB  - Continuous repeated gate sweeping incorporated with substrate etching step is
      utilized to decrease the OFF state current in single-walled carbon nanotube field
      effect transistors with bundled carbon nanotubes. In particular, the effects of
      continuous repeated gate sweeping on transfer characteristic of transistors are
      examined. The etching step creates suspension in transistors at contact with
      metal electrodes as well as causing some single-walled carbon nanotubes to
      dramatically burn off by electrical current. By repeating gate sweeping, source
      drain current gets smaller and smaller. This will eventually lead to the OFF
      state current less than 2 nA. Defects in the lattice of single-walled carbon
      nanotubes introduced by multiple gate sweeping could be the reason for this
      phenomenon. Contribution from possible hole trapping is also considered.

PMID- 22408945
TI  - Reduction of ordering temperature of self-assembled FePt nanoparticles by
      addition of Au and Ag.
AB  - The [FePt]94Au6 and [FePt]90Ag10 nanoparticle arrays were synthesized on Si
      substrates by a reverse micellar method, combined with plasma treatment and in
      situ deposition of a SiO2 overlayer, and the post annealing step was performed to
      drive the face-centered cubic to tetragonal phase transition. These FePt
      nanoparticles exhibit a quasi-hexagonal order with tailored inter-particle
      spacing and particle size. The effects of the Ag and Au on the structural and
      magnetic properties of FePt were investigated. The results indicate that both Au
      and Ag additives can remarkably enhance the coercivity and reduce the ordering
      temperature, however, the optimum composition is different for them. The optimum
      composition is determined to be [FePt]94Au6 and [FePt]90Ag10, respectively, for
      which the ordering temperature of FePt nanoparticles is reduced by -100 degrees
      C. After 600 degrees C annealing, the [FePt]94Au6 and [FePt]90Ag10 nanoparticles
      are totally ferromagnetic with apparent larger coercivities of -7.0 kOe, which is
      about 3.8 kOe larger than that of the pure FePt nanoparticles. The mechanism of
      the chemical ordering acceleration may be attributed to the defects and strains
      caused by the Au/Ag additives.

PMID- 22408946
TI  - Reduced distribution of threshold voltage shift in double layer NiSi2
      nanocrystals for nano-floating gate memory applications.
AB  - We report on the fabrication and capacitance-voltage characteristics of double
      layer nickel-silicide nanocrystals with Si3N4 interlayer tunnel barrier for nano
      floating gate memory applications. Compared with devices using SiO2 interlayer,
      the use of Si3N4 interlayer separation reduced the average size (4 nm) and
      distribution (+/- 2.5 nm) of NiSi2 nanocrystal (NC) charge traps by more than 50%
      and giving a two fold increase in NC density to 2.3 x 10(12) cm(-2). The
      increased density and reduced NC size distribution resulted in a significantly
      decrease in the distribution of the device C-V characteristics. For each program
      voltage, the distribution of the shift in the threshold voltage was reduced by
      more than 50% on average to less than 0.7 V demonstrating possible multi-level
      cell operation.

PMID- 22408947
TI  - Reversible ferromagnetism study in un-doped ZnO thin films.
AB  - Room temperature ferromagnetism in pure ZnO thin films prepared by spin-coating
      method was observed. X-ray photoelectron spectroscopy and inductively coupled
      plasma-mass spectrometry showed no or extremely little presence of impurities,
      which were unlikely to be responsible for the large magnetization moment
      observed. In order to study the origin of ferromagnetism, ZnO thin films were
      rapidly annealed in N2 and O2 ambient in a repetitive way. Electrical and
      magnetic performance after each annealing was measured. It is found that
      ferromagnetism is diminished and re-appeared, in accordance with the decrease and
      increase of conductivity. Cathodoluminescence spectra show evidence of reversible
      variation of oxygen vacancy defect in the annealing process. These results
      provide strong evidence that oxygen vacancies play a significant role in inducing
      ferromagnetism in ZnO thin films.

PMID- 22408948
TI  - Crystallization and electrical characteristics of 0.95 (Na0.5Bi0.5)TiO3-0.05
      BaTiO3 thin films under different annealing temperature and atmosphere.
AB  - 0.95 (Na0.5Bi0.5)TiO3-0.05 BaTiO3 +1 wt% Bi2O3 (NBT-BT3) ceramic is used as
      target to deposit the NBT-BT3 thin films. The excess 1wt% Bi2O3 is used to
      compensate the vaporization of Bi2O3 during the sintering and annealing
      processes. NBT-BT3 thin films are successfully deposited using radio frequency
      (RF) magnetron sputter method and crystallized subsequently using a conventional
      furnace annealing (CFA) process. The annealed process is conducted in air and in
      oxygen atmosphere at temperatures ranging from 600-800 degrees C for 60 min. As
      compared with the as-deposited NBT-BT3 thin films, the CFA-treated process has
      improved the grain growth and crystallization. We will show that the annealing
      atmosphere is the more important parameter to influence the grain growth and
      crystallization of NBT-BT3 thin films than the annealing temperature. The
      influences of CFA-treated temperature and atmosphere on the electrical
      characteristics of NBT-BT3 thin films, including the polarization characteristics
      (Pr, Ps, and Ec values), the capacitance-voltage (C-V) curves, and the leakage
      current density-electric field (J-E) curves, are also investigated in this study.

PMID- 22408949
TI  - The influences of particle sizes on the dielectric properties of
      PEI/(Ba0.8Sr0.2)(Ti0.9Zr0.1)O3 composites.
AB  - In order to investigate the embedded capacitors with higher capacitance value in
      the future, two technologies of increasing the dielectric constant of filler and
      decreasing the thickness of capacitors can be combined to develop a best method.
      For that, the high dielectric constant of (Ba0.8Sr0.2)(Ti0.9Zr0.1)O3 (BSTZ)
      ceramic powders with three different sizes (3 microm, 200 nm, and 100 nm) are
      used as the filler to mix with polyetherimide (PEI) to form the PEI/BSTZ
      composites. The dielectric constants and loss tangents of PEI/BSTZ composites
      with different contents of BSTZ ceramic powders are measured using the plate
      method. As the contents of BSTZ powders increase from 10 wt% to 70 wt%, the
      dielectric constants and loss tangents of PEI/BSTZ composites increase with the
      increase content of BSTZ ceramic powders, independent on the particle sizes. As
      the BSTZ content is less than and equal to 50 wt% and same loading ratio is used,
      the dielectric constants of PEI/200 nm-BSTZ and PEI/100 nm-BSTZ composites are
      large than those of PEI/3 microm-BSTZ composites. In this study, the Lichtenecker
      logarithmic mixing rule is also used to fit the measured results and predict the
      dielectric constants of PEI/BSTZ composites.

PMID- 22408950
TI  - The research of manufacture of flexible conductive tracks at room temperature.
AB  - Nano silver is widely used in conductive lines for its advantages, nano size, low
      melt temperature and excellent conductivity. In general, nano silver of less than
      50 nm need be sintered at 200 centigrade in order to acquire conductivity, but it
      limits the choice of the substrates, only high temperature resistant substrate
      can be used, for example, PI film and glass. In order to acquire flexible tracks
      with excellent conductivity at room temperature on paper and PET, nano silver
      emulsion of 2 percent silver content was prepared through liquid phase chemical
      reduction, and then the concentration of silver was improved to 17 percent by
      centrifuging at high speed. And the emulsion was adjusted to meet the demand of
      inkjet printing, such as surface tension, and viscosity, pH value, then was
      jetted onto photo paper and PET film. High conductivity was acquired after
      treated by 830 nm infrared laser, and the sheet resistance is less than 2
      omega/(see symbol). After aging test, the conductivity was stable. The method can
      be used in solar cells, flexible LED, intelligent packaging and can replace the
      traditional screen printing method at low cost.

PMID- 22408951
TI  - Temperature dependence of silver nanostructure for surface enhanced Raman
      scattering application.
AB  - We study the fabrication and application of the fractal silver nanostructure
      using an electrochemical process. Scanning electron microscope and high
      resolution transmission electron microscope images show the morphology of silver
      nanostructure can be well controlled via the various reaction times. The surface
      enhanced Raman scattering of 10 microM aqueous Rhodamine 6G (R6G) solutions
      conducted in as-fabricated silver nanostructure achieved an enhancement factor
      approximately 10(5) at room temperature. Meanwhile, an approximately 10(4)
      enhancement factor of SERS signal can be kept under 200 degrees C in present
      study. This study can help us to integrate the nano-metals and nano-particles for
      advanced nano devices.

PMID- 22408952
TI  - Polymer film selection for corrosion protection of data storage magnetic
      materials.
AB  - Due to the current requirement of high recording density of hard disk drive, the
      thickness of DLC layer which is the protective layer is needed to be reduced.
      Therefore, the corrosion of read-write elements that are fabricated from soft
      magnetic materials is more critical. During the photolithography process, polymer
      photoresist is playing the major role on controlling the corrosion of soft
      magnetic materials. Two different types of polymer photoresists are selected to
      investigate, noted as wet photoresist and dry photoresist, respectively. Contact
      angle measurement, AFM and SEM are techniques using to determine the quality of
      polymer photoresists. Furthermore, the direct corrosion is also studied by using
      potentiostat/galvanostat-based measurements. The result suggested that the wet
      photoresist, AZ4999 Clariant, is better as compared to that of dry photoresist.
      No surface degradation as well as surface defects of the wet photoresist was
      found after lithography process. The corrosion rate of the specimen coated by
      this corresponding wet film is found to be only 1.44 x 10(-6) mm/y. In addition,
      the wet photoresist surface is hydrophobic posed of more than 75 degree of
      contact angle.

PMID- 22408953
TI  - Photoreflectance study of strained GaAsN/GaAs T-junction quantum wires grown by
      metal-organic vapor phase epitaxy.
AB  - Strained GaAsN T-junction quantum wires (T-QWRs) with different N contents grown
      on GaAs by two steps metal-organic vapor phase epitaxy in [001] and [110]
      directions, namely QW1 and QW2 respectively, have been investigated by
      photoreflectance (PR) spectroscopy. Two GaAsN T-QWRs with different N contents
      were formed by T-intersection of (i) a 6.4-nm-thick GaAs0.89N0.011 QW1 and a 5.2
      nm-thick GaAs0.968N0.032 QW2 and (ii) a 5.0-nm-thick GaAs0.985N0.015 QW1 and a
      5.2-nm-thick GaAs0.968N0.032 QW2. An evidence of a one-dimensional structure at T
      intersection of the two QWs on the (001) and (110) surfaces was established by PR
      resonances associated with extended states in all the QW and T-QWR samples. It is
      found that larger lateral confinement energy than 100 meV in both of [001] and
      [110] directions were achieved for GaAsN T-QWRs. With increasing temperature, the
      transition energy of GaAsN T-QWRs decreases with a faster shrinking rate compared
      to that of bulk GaAs. Optical quality of GaAsN T-QWRs is found to be affected by
      the N-induced band edge fluctuation, which is the unique characteristic of dilute
      III-V-nitrides.

PMID- 22408954
TI  - An artificial nose based on M-porphyrin (M = Mg, Zn) thin film and optical
      spectroscopy.
AB  - Artificial nose has recently become an emerging instrument for quality assurance
      in the food industry. These paper present the optical gas sensors based on
      Magnesium-5, 10, 15, 20-tetra phenyl-porphyrin (MgTPP) and Zinc-5, 10, 15, 20
      tetra phenyl-porphyrin (ZnTPP) thin films and their application as an artificial
      nose. Based on the measurement of optical absorbance response using a general UV
      Vis spectroscopy, this artificial nose was tested to discriminate various
      volatile organic compounds (VOCs) and Thai beverages. Atomic force microscopy
      (AFM) and X-rays diffraction (XRD) were used to confirm the polycrystalline
      structure of the sensing materials. Density functional theory (DFT) calculations
      reveal that MgTPP interacts more strongly with the VOCs than ZnTPP, especially
      with methanol. The classification results of VOCs and Thai beverage vapors using
      the principal component analysis indicate that both MgTPP and ZnTPP-based
      artificial noses can be an efficient tool for quality assurance of alcoholic
      beverages.

PMID- 22408955
TI  - Stress-induced wurtzite to hexagonal phase transformation in zinc oxide
      nanowires.
AB  - The stress-induced wurtzite to hexagonal phase transformation in [0110] oriented
      zinc oxide nanowires were investigated using a molecular dynamics simulation and
      reactive force field potentials. The yield strength of the 2.13 x 1.93 nm
      wurtzite nanowires is 12 GPa at 50 K. The wurtzite to hexagonal phase
      transformation was successfully observed at stress plateaus (5-5.5 GPa at 50 K)
      located after the yield point of the wurtzite phase. The wurtzite to hexagonal
      phase transformation was a result of the propagation of {0111} twinning
      boundaries. During the phase transformation, the wurtzite and hexagonal phases
      were clearly separated by the {0111} twinning boundaries. To analyze the
      difference between ceramic and metallic systems, all the calculation data of
      wurtzite to hexagonal transformation were compared with stress-induced phase
      transformation in metallic nanowires such as CuZr and NiA1. As the result of the
      [0110] tensile loading of the ZnO nanowires, the hexagonal phase was obtained.

PMID- 22408956
TI  - Surface property change of C doped TiO2 nano-pillars by O2 plasma treatment.
AB  - TiO2 surface is led to super-hydrophilic surface by modifying to hydroxyl group.
      The super-hydrophilic surface can be applied to anti-fogging, because of
      preventing formation of water droplet on the surface. Super-hydrophilic coatings
      are made of metal oxides, polymers, or their mixtures. In this study, columnar
      structured C doped TiO2 nano-pillars were grown on glass substrates by MOCVD
      method. For change of surface properties, grown columnar-structured C-TiO2 nano
      pillars were treated by oxygen plasma. After oxygen plasma treatment, the surface
      property of grown columnar structured C-TiO2 nano-pillars changed from
      hydrophobic surface to super hydrophilic surface. For determination of this
      mechanism, scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray
      photoelectron spectroscopy (XPS), FT-IR spectroscopy, and contact angle analyzer
      were employed.

PMID- 22408957
TI  - Roll to roll fabrication of thin film silicon solar cells on nano-textured
      substrates.
AB  - ECN is developing a novel fabrication process for thin film silicon solar cells
      on steel foil. Key features in this process are: (1) application of an insulating
      barrier layer which enables monolithic interconnection and texturization of the
      rear contact with submicron structures for light trapping; (2) Si deposition with
      remote, linear PECVD; (3) series interconnection by laser scribing and printing
      after deposition of all layers, which reduces the total number of process steps.
      The barrier layer is essential for the monolithic series interconnection of
      cells, but we show that it also enables optimum light trapping in the solar
      cells. We can fabricate any arbitrary sub-micron surface profile by hot embossing
      the barrier layer. For deposition of doped and intrinsic silicon layers we use
      novel remote, linear plasma sources, which are excellently suited for continuous
      roll-to-roll processing. We have been able to fabricate device-quality amorphous
      and microcrystalline silicon layers with these sources. The first nip a-Si cells
      were made on steel substrates with flat barrier layer and had initial
      efficiencies of 6.3%, showing the potential of the concept.

PMID- 22408958
TI  - Effects of QD concentrations and thermal annealing on the performance of self
      assembly QD-OLEDs.
AB  - We have fabricated and investigated the effect of CdSe/ZnS quantum dot (QD)
      concentrations on the performance of self-assembly hybrid inorganic/organic light
      emitting diodes (QD-OLEDs). The uniform distribution of QDs with controllable
      density was achieved using the conventional spin-coating method. There was a QD
      threshold concentration for the emission of QDs in QD-OLED. Below that threshold
      concentration we did not observe the QD emission from the QD-OLED. The best
      performance of QD-OLED was found for the QD concentration of -9 x 10(11) cm(-2).
      The QD electroluminescence intensity was increased about three times after the
      annealing of QD-OLED at 80 degrees C for about 20 minutes in nitrogen atmosphere.
      The QD electroluminescence peak energy was remain same before and after the
      annealing of QD-OLED. The maximum external quantum efficiency was around 2.1%.
      The effect of process parameters and the QD emission mechanism are discussed.

PMID- 22408959
TI  - Electronic structures of well-aligned Er-doped ZnO nanorod arrays.
AB  - Electronic structures of well-aligned Er-doped ZnO (ZnO:Er) nanorod arrays (NRAs)
      synthesized by a solution-based hydrothermal process were characterized by high
      resolution transmission electron microscopy (HRTEM) and X-ray absorption fine
      structure (XAFS). HRTEM and angular dependent X-ray absorption near-edge
      structure analysis at O K and Zn L3 edges indicates that the spontaneous
      polarization is along the [0001] direction. The analysis of Er L3-edge XAFS
      demonstrates that the local structure around Er in the ZnO:Er NRAs was
      transformed from O(h) to C(4v), after annealing.

PMID- 22408960
TI  - Effect of nano anhydrous magnesium carbonateon fire-retardant performance of
      polylactic acid/bamboo fibers composites.
AB  - Polylactic acid/bamboo fibers (PLA/BF) composites, which are extremely flammable,
      must be carried out fire-retardant processing. However, traditional organic flame
      retardants release certain amount of pollutant to the environment, and inorganic
      flame retardants require more addition, which influenced the mechanical
      properties of composites. Therefore, nano inorganic flame retardants, which have
      some characteristics of small size, uniform shape and high specific surface area,
      can bring good flame-retardant effect with relatively few addition. Meanwhile, it
      can enhance the interaction of composites interface, and disperse more evenly in
      polylactic acid matrix. Furthermore, it has light influence on the physical
      mechanical properties. In this study, nano anhydrous magnesium carbonate (NAMC)
      is used as flame retardant, Cone Calorimeter and Dynamic Thermal Mechanical
      Analyzer are adopted for studying the fire-retardant properties and the dynamic
      thermodynamic parameters of the polylactic acid/bamboo fiber composites,
      respectively. Results show that nano anhydrous magnesium carbonate flame
      retardant have good fire-retardant performance for the polylactic acid/bamboo
      fiber composites, considering practicality and economy, its ideal addition is 5%.

PMID- 22408961
TI  - Metal (Li, Al, Ca and Ti) absorbed graphene with defects for hydrogen storage:
      first-principles calculations.
AB  - The characteristics of Li, Al, Ca and Ti metal adsorption on graphene with boron
      substitution and various vacancy defects are investigated using density
      functional theory calculation. Hydrogen adsorption characteristics and electronic
      structure of H2/metal adsorbed graphene were also calculated. It was found that
      Li, Al, Ca and Ti metal atoms are well dispersed on the graphene and can form a
      (2 x 2) pattern because clustering of metal atoms is hindered by the repulsive
      Coulomb interaction between the metal adatoms and the strong bonding force
      between the dispersed metal atom and graphene. Ca and Ti metal adatom show strong
      binding energy with the graphene in the cases of B substitution and specific
      vacancy, respectively. Ca and Ti were also found to be able to 8H2 molecules on
      the double side of the boron substituted graphene. This allows for a storage
      capacity of a 8.5 and 7.9 wt% hydrogen for Ca and Ti adatom, respectively.

PMID- 22408962
TI  - RecA protein mediated nano-scale patterning of DNA scaffolds.
AB  - Molecular lock-and-key functionality inherent to a large number of biological
      molecules is arguably one of the most promising potential routes for building
      complex nanostructures and eventually nano-electronic devices by self-assembly.
      Here, we report the use of the DNA-binding protein RecA as a tool for patterning
      DNA scaffolds site-specifically and in a programmable way at the nanometre-scale.
      This is demonstrated by patterning a 3 kilo-base-pair double-stranded DNA
      molecule at ten different locations with nanometre-sized RecA-based nucleoprotein
      filaments. This protein-based molecular patterning technique, which is site
      specific, programmable, and scalable, offers a potential basis for molecular
      lithography applications, and opens previously inaccessible routes towards the
      fabrication of complex functional nano-electronic devices by self-assembly.

PMID- 22408963
TI  - A portable electrochemical sensor for caffeine and (-)epigallocatechin gallate
      based on molecularly imprinted poly(ethylene-co-vinyl alcohol) recognition
      element.
AB  - The U.S. Food and Drug Administration allows a maximum of 72 mg of caffeine per
      12 oz. serving (6 mg/oz). Consuming 400 mg of caffeine 3 times daily for 7 days
      may develop sleep disruption effects. However, it is still very hard for people
      to estimate how much caffeine is intake daily. Moreover, (-)epigallocatechin
      gallate (EGCG) is studied a potent antioxidant that may have therapeutic
      properties for anti-aging and cancer. Conventionally, both caffeine and EGCG
      could be measured by the protocols of high performance liquid chromatography;
      however, high precision instruments are required. In this work, the caffeine and
      EGCG are used as the template molecules and imprinted into poly(ethylene-co-vinyl
      alcohol), EVAL, via solvent evaporation. The EVAL membrane is then used as the
      sensing element for electrochemical analysis after templates removal. From the
      cyclic voltammetry measurement of the caffeine, the peak oxidation potential is
      shifted from 0.36 to 0.46 V when the final concentration of caffeine is from 0.01
      to 1 mg/mL, and the highest current density is about 0.18 microA/cm2. The
      caffeine and EGCG concentrations measured in three real samples are about 0.10
      0.13 mg/mL and 0.49-1.74 mg/mL, respectively. This molecularly imprinted
      polymeric coated electrode is potential employed as a home-care system.

PMID- 22408964
TI  - Surface cleaning of the nanowire field-effect transistor for gene detection.
AB  - The efficiency of DNA immobilization by using various surface cleaning methods is
      studied in this work. The degree of surface cleaning is evaluated by the surface
      tension measurement to reveal the contribution from the polar and apolar terms.
      The observation from the fluorescent microscope images indicates the
      effectiveness of surface clean by the acetone and ethanol mixtures, as well as
      the sulphuric acid and hydrogen peroxide mixtures. We also fabricate a series of
      back-gated, 60-nm nanowired (NW) field-effect transistor (FET) sensors for
      mutation gene detection by following the developed acetone and ethanol mixtures.
      Electrical properties of the NWFET sensor demonstrate the n-channel depletion
      characteristics. The current of the sensor is reduced once the attachment of
      negative charge molecules. The single-stranded capture DNA is chemically
      immobilized onto the surface of silicon NWFET by three-step reactions. The sensor
      surface demonstrates the great performance of current shift after the suitable
      cleaning. The NWFET sensor is successfully applied to detect the BRAF(V599E)
      mutation genes from the hybridized processes. The sensing behaviour estimated
      from the electrical signal reaches the femtomolar level.

PMID- 22408965
TI  - Mechanical, thermal and bioactive behaviors of polyamide 6/hydroxyapatite
      nanocomposites.
AB  - Polyamide-6 nanocomposites filled with different hydroxyapatite nanorod contents
      were injection molded. The thermal and tensile properties as well as bioactivity
      of such nanocomposties were investigated. The results showed that the thermal
      stabilities of polyamide-6 improve considerably by adding hydroxyapatite
      nanorods. Tensile measurements demonstrated that nanorods reinforce polyamide-6
      effectively but reduce its tensile elongation and impact strength. Cell
      cultivation and viability tests showed that mouse osteoblasts adhere and
      proliferate readily on the nanocomposites containing high filler contents.
      Therefore, polyamide-6/hydroxyapatite nanocomposites show potential application
      in orthopedics for bone tissue replacements.

PMID- 22408966
TI  - Al doped ZnO nanogranular film fabricated by layer-by-layer self-assembly method
      and its application for gas sensors.
AB  - ZnO is one of the most promising materials for gas sensor. Nanogranular films
      with ultrahigh surface-to-volume ratio have great potential in gas sensor
      application. In this paper, Al doped ZnO nanogranular films were fabricated by
      layer-by-layer (LBL) self-assembly method and the gas sensitivity of ZnO films
      were investigated. The results show that sensitivity of Al:ZnO gas sensors is up
      to 12 against 20000 ppm hydrogen, while the response time and recovery time of
      the sensor are only 12 s and 25 s respectively. The high sensitivity is
      attributed to the high surface-to-volume ratio of nanogranular and porous
      structure of self-assembled films.

PMID- 22408967
TI  - Crystallization kinetics of amorphous Ga-Sb films extended for phase-change
      memory.
AB  - Performance of phase-change materials based on Ga-Te-Sb was found getting better
      with decreasing Te content in our earlier studies. We concerned much properties
      of Te-free, Sb-rich binary Ga-Sb, which has been known to possess extremely fast
      crystallization behavior. Non-isothermal and isothermal crystallization kinetics
      of amorphous Sb-rich Ga-Sb films were explored by temperature dependent
      electrical resistance measurements. The crystallization temperature (183 to 261
      degrees C) increases with decreasing Sb content (91 to 77 at%). The activation
      energy and rate-factor vary with Sb contents and reach the maximum at Ga19Sb81.
      The kinetic exponent is smaller than 1.5 at Sb < 85 at% denoting that the
      mechanism is one-dimensional crystal-growth from nuclei. The temperature
      corresponding to 10-year data-retention, evaluated from films, is 180 degrees C
      (Ga19Sb81) and 137 degrees C (Ga13Sb87), respectively. We verified memory
      performance using test-devices made of Ga16Sb84 working at voltages with 100 ns
      pulse-width.

PMID- 22408968
TI  - Dependence of electrical properties on thermal temperature in nanocrystalline
      SnO2 thin films.
AB  - Nanocrystalline SnO2 thin films were prepared by pulsed laser deposition
      techniques on clean glass substrates, and the films were then annealed for 30 min
      from 50 to 550 degrees C with a step of 50 degrees C, respectively. The
      investigation of X-ray diffraction confirmed that the various SnO2 thin films
      were consisted of nanoparticles with average grain size in the range of 23.7-28.9
      nm. Root-mean-square surface roughness of the as-prepared SnO2 thin film was
      measured to be 25.6 nm which decreases to 16.2 nm with thermal annealing.
      Electrical resistivity and refractive index were measured as a function of
      annealing temperature, and found to lie between 1.24 to 1.45 momega-cm, and 1.502
      to 1.349, respectively. The results indicate that nearly opposite actions to root
      mean-square surface roughness and electrical resistivity make a unique
      performance with thermal annealing temperature. The post annealing shows greater
      tendency to affect the structural and electrical properties of SnO2 thin films
      which composed of nanoparticles.

PMID- 22408969
TI  - Effects of device and peripheral parameters on transconductance of silicon
      nanowire transistors.
AB  - This paper presents a general analysis over the transconductance function in
      silicon nanowire transistors (SNWTs). The transconductance function in SNWTs has
      been well-discussed and the relation between this function and the physical and
      peripheral parameters of the SNWT has been precisely investigated. The
      transconductance expression has been derived as a function of device parameters
      (e.g., oxide capacitor, electron effective-mass) and applied voltage biases,
      which helps to understand the essential physics of one-dimensional (1D) nanowire
      FETs and to interpret numerical simulation results. These simulations demonstrate
      the transconductance formulation as a function of environmental temperature,
      voltage biases and oxide layer thickness.

PMID- 22408970
TI  - Electrical conductivity of polyvinylidene fluoride nanocomposites with carbon
      nanotubes and nanofibers.
AB  - Polyvinylidene fluoride nanocomposites with low loading levels of pristine
      multiwalled carbon nanotubes, carboxyl functionalized multiwalled carbon
      nanotubes and vapor grown carbon nanofibers were prepared by a versatile
      coagulation method. The alternating current electrical conductivity of these
      composites in the frequency range of 40-12 MHz was investigated. The alternating
      current conductivity of percolating nanocomposites followed a universal dynamic
      response. Therefore, both the direct current plateau and frequency dependent
      regime were observed. The percolation threshold of three composite systems was
      determined to be 1.0, 0.98, and 1.46 vol.%, respectively. Moreover, the
      percolative nanocomposites exhibited nonlinear current-voltage responses,
      demonstrating the presence of tunneling conduction.

PMID- 22408971
TI  - Improved infrared emissions of Er(3+)-Tm3+ co-doped Al2O3 thin films: the role of
      cross relaxation among rare earth ions.
AB  - We report the infrared emissions of Er(3+)-Tm3+ co-doped amorphous Al2O3 thin
      films pumped at 791 nm by a Ti:sapphire laser. The as-deposited films were
      annealed to improve the photoluminescence performance. Three cross relaxation
      channels among Er(3+)-Tm3+ and Tm(3+)-Tm3+ ions incorporated in the films were
      investigated as annealing temperature increases especially from 800 to 850
      degrees C. In order to understand the Stark effect and cross relaxations, the
      photoluminescence spectra were deconvoluted by Gaussian fittings. Our results
      indicate that the luminescence intensity of 1.62 microm in comparison to 1.5
      microm can be enhanced by the cross relaxation process [Er3+ (4I13/2) + Tm3+
      (3H6) --> Er3+ (4I15/2) + Tm3+ (3F4)], and the longer-wavelength side of Er3+
      emission can be improved by the CR process [Er3+ (4I15/2) + Tm3+ (3H4) --> Er3+
      (4I3/2) + Tm3+ (3F4) at expense of the Tm3+ 1.47 microm emission which is also
      maybe quenched by the CR effect between themselves. These results suggest one
      possible approach to achieve broadband infrared emissions at the wavelength
      region of 1.45-1.65 microm from the Er(3+)-Tm3+ co-doped systems.

PMID- 22408972
TI  - Fabrication of ion-induced carbon-cobalt nanocomposite fibers: effect of cobalt
      supply rate.
AB  - Graphite surfaces were irradiated by argon (Ar+) ions at 1 keV with a
      simultaneous cobalt (Co) supply at room temperature. Various kinds of carbon
      nanocomposites, such as nanocones with and without single nanofibers on their
      tops, nanorods and fish-scale-like nanoprotrusions, were formed depending on Co
      supply rates. It has been observed that with increasing the Co supply rate the
      formation of nanoprotrusions without nanofibers became prominent. Both nanofibers
      and nanoprotrusions were surely composed of carbon and Co, as confirmed by energy
      dispersive X-ray analysis. The cobalt carbon nanocomposite fibers (CCNFs), -1.5
      microm in average length, were grown on the top of the nanocones at the Co supply
      rate of 1.0 nm/min. The field electron emission characteristics of CCNFs thus
      grown indicated that there is an optimum parameter for the CCNF growth to achieve
      the better emission performance than that of pristine Ar(+)-induced carbon
      nanofibers.

PMID- 22408973
TI  - Investigation of influence of synthesis parameters on length and purity of the
      carbon nanotubes.
AB  - In this article, a systematic study was conducted to understand the influences of
      various synthesis parameters, such as catalyst pretreatment time, growth time,
      growth temperature, reaction gas flow rate on length and quality of the carbon
      nanotubes grown by thermal chemical vapor deposition (TCVD). Carbon nanotube
      (CNT) grown on Fe deposited on silicon substrates were characterized by scanning
      electron microscope and Raman spectroscopy. It was found that all of the
      synthesis parameters investigated had effects on both length and quality of the
      carbon nanotube. After optimizing the various thermal chemical vapor deposition
      synthesis parameters, long carbon nanotube arrays of up to 150 microm in length
      were successfully synthesized and possess the potential application in multi
      level interconnects.

PMID- 22408974
TI  - Fabrication of CoPt ultra-sharp single atom tips.
AB  - Two kinds of new nano tips with potential to magnetic application are fabricated.
      One is a PtCo alloy pyramidal tip formed by surface faceting, the other is a Pt
      based Co tip formed by the epitaxy with a proper growth mode. Ultra high vacuum
      field ion microscopy with atomic resolution is used to investigate the atomic
      structures of the tip apex after various sharpen treatments.

PMID- 22408975
TI  - Photocatalytic decompositions of gaseous HCHO over Ag/TiO2 nanotube arrays.
AB  - TiO2 nanotube arrays prepared by electrochemical anodization method attract
      considerable interest as a practical air purifier, as the nanotube arrays may
      form a TiO2 film with a porous surface and straight gas diffusion channel. Here,
      the TiO2 and Ag/TiO2 nanotube arrays with different Ag amount are used to degrade
      gaseous HCHO pollutants. The photocatalytic results confirm that the HCHO
      degrading efficiency of the TiO2 nanotube arrays may vary with the amount of Ag
      nanoparticles, and the Ag amount within a certain range significantly improves
      the degradation rate of HCHO molecules. The main final product after HCHO
      degradation is detected to be CO2. Ag nanoparticles effectively act as electron
      trappers prohibiting the recombination of photo-excited electrons and holes,
      hence increasing the photocatalytic efficiency. However, excessive Ag
      nanoparticles form new recombination center of photo-excited electrons and holes
      to decrease the photocatalytic efficiency.

PMID- 22408976
TI  - Nearly monodispersed perylene nanotablets: easy fabrication and unique optical
      properties.
AB  - Here we describe a simple physical vapor deposition (PVD) method to prepare large
      quantity of highly monodispersed perylene nanotablets with a deposition
      temperature controlled approach. The nanotablets produced are 1 microm octagon
      with 100-200 nm thickness. Confocal microscopic images of the nanotablets excited
      with a UV light show not only yellow color emission which is quite different from
      perylene monomers but also the obvious light-wave guiding properties. The
      formation of beta form nanocrystals shows that our method is highly selective for
      only one kind of perylene nanocrystals, which makes sure the uniform optical and
      electronic properties of the whole thin film. The morphology of the unique
      perylene nanotablets is significantly decided by the strictly required
      temperature of the depositing substrates. This approach is simple and template
      free and the as-prepared nanotablets possess smooth surface. The coating of the
      nanotablets can change the superhydrophilic surface to a superhydrophobic one
      which is an important application property for fabricating stable nanodevices.

PMID- 22408977
TI  - High performance light-colored nitrile-butadiene rubber nanocomposites.
AB  - High mechanical performance nitrile-butadiene rubber (NBR) with light color was
      fabricated by the method of in situ formation of zinc disorbate (ZDS) or
      magnesium disorbate (MDS). The in situ formed ZDS and its polymerization via
      internal mixing was confirmed by X-ray diffaraction. The mechanical properties,
      ageing resistance, morphology and the dynamic mechanical analysis were fully
      studied. It was found that with increasing loading of metallic disorbate both the
      curing rate and the ionic crosslink density was largely increased. The modulus,
      tensile strength and tear strength were largely increased. With a comparison
      between internal mixing and opening mixing, the mechanical performance for the
      former one was obviously better than the latter one. The high performance was
      ascribed to the finely dispersion nano domains with irregular shape and obscure
      interfacial structures. Except for the NBR vulcanizate with a high loading of
      MDS, the others' ageing resistance with incorporation of these two metallic
      disorbate was found to be good. Dynamic mechanical analysis (DMA) showed that,
      with increasing loading of metallic disorbate, the highly increased storage
      modulus above -20 degrees C, the up-shifted glass transition temperature (Tg) and
      the reduced mechanical loss were ascribed to strengthened interfacial
      interactions.

PMID- 22408978
TI  - Synthesis of BaCO3 nanowires and their humidity sensitive property.
AB  - Barium carbonate (BaCO3) nanowires have been synthesized for the first time by
      using the composite hydroxide mediated (CHM) method. The products are
      characterized by X-ray diffraction (XRD), field emission scanning electron
      microscopy (FE-SEM), and transmission electron microscopy (TEM). Humidity sensors
      based on BaCO3 nanowires have been fabricated. The response to humidity in static
      and dynamic measurement proves the ultrasensitive property of the sensors. The
      resistance changes from 386 M(omega) to 7.1 M(omega) as the relative humidity
      (RH) increases from 20% to 95%. The response and recovery time of the resistance
      is 16 s and 56 s versus the changes of relative humidity from 25% to 85%. These
      results indicate promising applications of BaCO3 nanowires in a highly sensitive
      environmental monitoring and humidity control electronic device.

PMID- 22408979
TI  - Electronic structure, electron field emission and magnetic behaviors of carbon
      nanotubes fabricated on La0.66Sr0.33MnO3 (LSMO) for spintronics application.
AB  - This work elucidates the electronic structure, electron field emission and
      magnetic anisotropic behaviors of single wall carbon nanotubes (SWCNTs) for the
      spin-electronics device application grown on the La0.66Sr0.33MnO3 (LSMO)/SrTiO3
      (STO) substrate. Micro-Raman spectroscopy, X-ray absorption near-edge structure
      (XANES) and valence-band photoemission spectroscopy (VBPES) were used for the
      study of electronics structure. The field emission characteristics were studied
      from the electron field emission current density (J) versus applied electric
      field (E(A)) from which the turn-on electric field (E(TOE)) was evaluated. The
      magnetization behaviors are also presented by the M-H hysteresis loop and were
      obtained by applying the magnetic field in the parallel and perpendicular
      direction of the CNTs at 305 K and 5 K temperatures. A magnetic measurement shows
      that the coercivity of the CNTs/LSMO/STO is higher and has hig anisotropic-nature
      than the composite LSMO/STO that could be the good material for the future
      possible spin-electronics device applications.

PMID- 22408980
TI  - Strong-coupling in inorganic-organic hybrid embedded single and coupled metallic
      microcavities.
AB  - Here we fabricated and studied highly-layered Inorganic-Organic Multiple Quantum
      Well structures and later placed them into metallic low quality factor
      microcavities. Room-temperature strong exciton-photon coupling is achieved in
      such single and coupled microcavities. Upon angle tuning, the broad photonic mode
      of the microcavities is clearly split into two modes at the exciton resonant
      absorption of hybrid perovskite. The large Rabi splitting upto -213 meV is
      obtained in good agreement with the theoretical models.

PMID- 22408981
TI  - Enhanced middle-infrared light transmission through Au/SiO(x)N(y)/Au aperture
      arrays.
AB  - The enhanced middle-infrared light transmission through Au/SiO(x)N(y)/Au aperture
      arrays by changing the refractive index and the thickness of a dielectric layer
      was studied experimentally. The results indicated that the transmission spectra
      was highly dependent on the refractive index and the thickness of SiO(x)N(y). We
      found that the transmission peaks redshifted regularly along with the refractive
      index from 1.6 to 1.8, owing to the role of surface plasmon polaritons (SPP)
      coupling in the Au/SiO(x)N(y)/Au cascaded metallic structure. Simultaneously, a
      higher transmission efficiency and narrower transmission peak was obtained in
      Au/SiO2.1N0.3/Au cascaded metallic structure with small refractive index (1.6)
      than in Au/SiO0.6N1/Au cascaded metallic structure with large refractive index
      (1.8). When the thickness of SiO(x)N(y) changes from 0.2 to 0.4 microm, the shape
      of transmission spectra exhibits a large change. It was found that a higher
      transmission efficiency and narrower transmission peak was obtained in
      Au/SiO(x)N(y)/Au cascaded metallic structure with a thin dielectric film (0.2
      microm), with the increase of SiO(x)N(y) film's thickness, the transmission peak
      gradually widened and disappeared finally. This effect is useful in applications
      of biochemical sensing and tunable integrated plasmonic devices in the middle
      infrared region.

PMID- 22408982
TI  - Near field imaging from multilayer lens.
AB  - Multilayer superlens has been reported that it had advantages over the single
      metal layer superlens. In this work, single silver layer and Ag-SiO2 multilayer
      superlens devices working at wavelength of 365 nm were fabricated using standard
      photolithography method. Grating objects with line/space (190 nm/190 nm)
      resolution could be resolved through both kinds of lens structures with working
      distance up to 128 nm. However, Ag-SiO2 multilayer lens shows higher
      transmittance and image contrast than the single silver layer device, the
      experimental result proves the theoretical calculation.

PMID- 22408983
TI  - Efficiency enhancement InGaP/GaAs dual-junction solar cell with subwavelength
      antireflection nanorod arrays.
AB  - The enhanced conversion efficiency of the InGaP/GaAs dual-junction solar cell was
      demonstrated utilizing broad-band and omnidirectional antireflection nanorod
      arrays. The nanorod arrays were fabricated by self-assembled Ni clusters,
      followed by inductively-coupled-plasma reactive ion etching. The conversion
      efficiency measured under one-sun air mass 1.5 global illuminations at room
      temperature was improved by 10.8%. The light absorption efficiencies of the top
      InGaP and bottom GaAs cells were also studied under the influence of nanorod
      arrays. The enhanced absorption efficiency was mostly contributed from the short
      wavelength absorption by top cell. Surface nanorod arrays served not only as
      broad-band omnidirectional antireflection layers but also scattering sources. The
      structure can be further optimized to obtain the maximum conversion efficiency.

PMID- 22408984
TI  - Optical and structural features of silicon-rich hydrogenated amorphous silicon
      nitride thin films.
AB  - A systematic study of fabrication and effect of post-deposition processing on the
      optical and structural features of silicon-rich hydrogenated amorphous silicon
      nitride thin films deposited by Hg-sensitized Photo-Chemical Vapour Deposition
      technique is presented. Both deposition parameters and post-deposition thermal
      treatment resulted into substantial change in the refractive index associated
      with the densification of the film. Our studies reveal that the presence of
      hydrogen and its out-diffusion upon thermal treatment play a crucial role in the
      overall structural evolution, specially the stabilization of individual phases
      such as Si and Si3N4. We further report the room-temperature photoluminescence
      from as-deposited films, which is due to formation of silicon nanostructures in
      crystalline and amorphous forms. These studies are of great interest from the
      prospective of commercially viable Si-based technology.

PMID- 22408985
TI  - Solution processed small molecule-based green phosphorescent organic light
      emitting diodes using polymer binder.
AB  - The authors have demonstrated efficient green organic light-emitting diodes
      (OLEDs) by using polymer binder. We fabricated small molecular green OLEDs and
      mixed polymer as a binder such as polystyrene (PS) or poly(N-vinylcarbazole)
      (PVK). The 4,4'-N,N'-dicarbazole-biphenyl (CBP) is a small molecular material
      with excellent electrical properties however it become crystalline at high
      temperature. Polymer binder prevents crystallization of CBP and lead to high
      efficiency. Therefore, we added PS or PVK into CBP as a polymer binder. As a
      result, we obtained maximum luminous efficiency, power efficiency and quantum
      efficiency of 22.8 cd/A, 11.6 Im/W and 6.61% at 23% PS added device.

PMID- 22408986
TI  - Fabrication of nano-structured HA/CNT coatings on Ti6Al4V by electrophoretic
      deposition for biomedical applications.
AB  - In order to improve the bone bioactivity and osteointegration of metallic
      implants, hydroxyapatite (HA) is often coated on their surface so that a real
      bond with the surrounding bone tissue can be formed. In the present study,
      cathodic electrophoretic deposition (EPD) has been attempted for depositing
      nanostructured HA coatings on titanium alloy Ti6Al4V followed by sintering at 800
      degrees C. Nano-sized HA powder was used in the EPD process to produce dense
      coatings. Moreover, multiwalled carbon nanotubes (CNTs) were also used to
      reinforce the HA coating for enhancing its mechanical strength. The surface
      morphology, compositions and microstructure of the monolithic coating of HA and
      nanocomposite coatings of HA with different CNT contents (4 to 25%) on Ti6Al4V
      were investigated by scanning-electron microscopy, energy-dispersive X-ray
      spectroscopy and Xray diffractometry, respectively. Electrochemical corrosion
      behavior of the various coatings in Hanks' solution at 37 degrees C was
      investigated by means of open-circuit potential measurement and cyclic
      potentiodynamic polarization tests. Surface hardness, adhesion strength and bone
      bioactivity of the coatings were also studied. The HA and HA/CNT coatings had a
      thickness of about 10 microm, with corrosion resistance higher than that of the
      substrate and adhesion strength higher than that of plasma sprayed HA coating.
      The properties of the composite coatings were optimized by varying the CNT
      contents. The enhanced properties could be attributed to the use of nano-sized HA
      particles and CNTs. Compared with the monolithic HA coating, the CNT-reinforced
      HA coating markedly increased the coating hardness without deteriorating the
      corrosion resistance or adhesion strength.

PMID- 22408987
TI  - Preparation and characterization of well ordered mesoporous diopside
      nanobiomaterial.
AB  - Well ordered mesoporous diopside (OMD) nanobiomaterial was synthesized by a sol
      gel process. The in vitro bioactivity of the OMD was evaluated by investigating
      the apatite-forming ability in simulated body fluid (SBF), and the hemostatic
      activity of the OMD was determined by measuring the activated partial
      thromboplastin time (APTT) and prothrombin time (PT) in vitro. The results
      suggested that the OMD exhibited excellent in vitro bioactivity, with surface
      apatite formation for OMD exceeding that of non-mesoporous diopside (n-MD) at 7
      days. Moreover, the OMD with high surface area possessed good hemostatic property
      because it could absorb a large number of water from the blood. In conclusion,
      the prepared OMD had excellent bioactivity and hemostatic activity, which can not
      only be applied as bone repair biomaterial for bone regeneration, but also as
      hemostatic agent for surgery hemostasis.

PMID- 22408988
TI  - Control release of bactericidal ion by an electronically driven system.
AB  - There is a dramatic proliferation of research related to electronically generated
      metallic bactericidal ions. Unfortunately, there are no literature reviews or
      discussions concerning metallic-nanoparticle suspension as a drug reservoir for
      iontophoretic applications. Heavy metals, especially silver, are frequently used
      to treat infection before the development of systemic antimicrobial agents. For
      medical applications, the conversion of colloidal silver into its ionic form is
      required; however, it does not directly use silver salts to provide the silver
      ions, due to the counter-ion (e.g., NO3-, SO4-) content of silver salts, which
      may cause severe problems to the body as the silver ion is consumed. The goal of
      this research is to develop an electronic dissociation system (EDS), which can
      provide a relatively safe bactericidal ion (Ag+) solution from the silver
      nanoparticles that has a controllable electric field. In this study, an ionic
      selective electrode (ISE) was used to observe and identify the details of the
      system activity throughout the course of the experiment. Both qualitative and
      quantitative data analyses were performed. The experimental data indicated that
      EDS can control the parameters of ion-releasing profiles, including the area
      under curve (AUC, dosage), rate of profile rise and fall, total dissociation
      time, peak time, and peak level concentration by a constant voltage (CV) mode or
      constant current (CC) mode. However, the CC mode was proved to be more
      controllable (an increase of 200 microA, equal to an increase of 1 ppm/hour), as
      the premeditated driving force is more precise, and relies on the current not
      voltage. This technology will be used to develop a chemical residue-free
      administration of control-released medical devices for iontophoretic
      applications.

PMID- 22408989
TI  - Preparation of a new nanosized As2O3/Mn0.5Zn0.5Fe2O4 thermosensitive
      magnetoliposome and its antitumor effect on MDA_MB_231 cells.
AB  - The purpose of our research is to explore the preparation method of a new
      nanosized As2O3/Mn0.5Zn0.5Fe2O4 thermosensitive magnetoliposome and study its
      antitumor effect on MDA_MB_231 cells. The liposomes prepared by the method of
      rotatory film and high-pressure homogenization were detected by transmission
      electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive
      spectrometry (EDS), nano-particles detector, atom fluorescence spectrophotometer
      and differential scanning calorimetry (DSC). The therapeutic effects of the
      nanosized thermosensitive magnetoliposomes combined hyperthermia on human
      MDA_MB_231 cells in vitro were evaluated by MTT assay and flow cytometry assay.
      The results indicated that the nanosized As2O3/Mn0.5Zn0.5Fe2O4 thermosensitive
      magnetoliposomes were prepared successfully. The liposomes were spherical, and
      most of them were single-room. The exat average diameter of them was 103.8 nm.
      EDS showed each nanosized As2O3/Mn0.5Zn0.5Fe2O4 thermosensitive magnetoliposome
      contained P, Mn, Zn, Fe, and As elements, and this proved liposomes have
      successfully entrapped As2O3 and Mn0.5Zn0.5Fe2O4. The encapsulation ratio of
      As2O3 detected by atom fluorescence spectrophotometer was 82.16%. The result of
      heating test showed that Mn0.5Zn0.5Fe2O4 can serve as a heating source upon
      alternating magnetic field (AMF) exposure leading the nanosized thermosensitive
      liposomes to reach its phase transition temperature (42.52 degrees C) and release
      As2O3. MTT assay and flow cytometry assay revealed that the therapeutic effect of
      the nanosized As2O3/Mn0.5Zn0.5Fe2O4 thermosensitive magnetoliposomes combined
      with hyperthermia upon AMF on MDA_MB_231 cells was much better than other groups.

PMID- 22408990
TI  - RGD-conjugated PLA-PLL nanoparticles targeting to Bacp-37 breast cancer
      xenografts in vivo.
AB  - Targeted delivery carriers are receiving considerable attention, the development
      of a more precise targeted delivery carrier is critical for the advancement of
      cancer chemotherapy. In this study, we evaluated the effects of RGD-conjugated
      poly (lactic acid-co-lysine)-(Arginine-Glycine-Aspartic) nanoparticles (PLA-PLL
      RGD NPs) on targeted delivery to Bacp-37 breast cancer bearing mice. PLA-PLL-RGD
      NPs were prepared by using the emulsion-solvent evaporation method. A subsequent
      MTT assay indicated that the NPs were non-toxic and had good biocompatibility. In
      vitro, the results of Confocal Laser Scanning Microscope (CLSM) and FAC Scan flow
      cytometry (FACS) indicated that the PLA-PLL-RGD NPs can bind more significantly
      to human umbilical vein endothelial cells, compared to PLA-PLL NPs. In vivo, the
      results of target imaging and biodistribution showed that PLA-PLL-RGD can
      significantly target to tumor of Bacp-37 breast cancer bearing mice. These
      results demonstrated that PLA-PLL-RGD NPs can effectively enhance targeted
      efficiency in vivo, and have the potential to be used as targeted delivery
      carrier.

PMID- 22408991
TI  - In situ comparative studies of self-assembly adsorption of bovine serum albumin
      on nano films by atomic force microscopy.
AB  - The self-assembly adsorption of function protein on crystal surfaces, as a common
      phenomenon, broadly takes place in many applications of biosensors, biocapsules
      and bioMEMS/bioNEMS. To systematically investigate the different adsorption
      characteristic of the same function protein on two different crystal surfaces
      under the identical environment, a hybrid surface composing silica and
      discontinuous Gold Nano Film (GNF) was fabricated by Physical Vapor Deposition
      (PVD) and ultrasonic cleaning method, where the dynamic process of the self
      assembly adsorption of Bovine Serum Albumin (BSA) was in situ observed by Atomic
      Force Microscope (AFM). The variations on the junction area of the two different
      surfaces were studied in the aqueous solution before and after injecting BSA with
      0.05 mg/ml concentration. It was found that silica, compared with same
      hydrophilic GNF, took on a fairly weak adsorption force. The results indicated
      that the adsorption strength of BSA on the hydrophilic crystal surface was
      determined not only by hydrophilic property, but also other interaction forces,
      like Van der Waals and so on. Moreover, observed under the contact mode of AFM,
      BSA adsorbed on GNF had great tendency to forming a ridge-like topography. These
      results may be helpful in the application of immunosensors and other areas.

PMID- 22408992
TI  - Nano-structured titanium coating for improving biological performance.
AB  - Nano-structured titanium coating was obtained by alkali treating the vacuum
      plasma sprayed samples following hot water immersing for 24 h. The influences of
      the surface microstructure on the biological performance were studied. A canine
      model was applied for in vivo evaluation of the bone bonding ability of the
      coatings. The histological examination results demonstrate that new bone was
      formed more rapidly on the nano-structured coating implants and grew into the
      porosity than the as-sprayed one. After 4 weeks implantation, the nano-structured
      implants were found to appose directly to the surrounding bone while large
      lacunae could still be observed at the interface between the as-sprayed samples
      and bone. All these results indicate that a nano-structured surface on the porous
      titanium coating is favorable for bone bonding.

PMID- 22408993
TI  - Effect of anodization voltage on electron field emission from carbon nanotubes in
      anodized alumina template.
AB  - In this work, electron field emission from AAO-CNT structure is studied as a
      function of anodizing voltage. It is found that the turn-on electric field of AAO
      CNTs reduces from 5 V/microm to 4 V/microm as anodization voltage increase from
      20 to 30 V. On the other hand, CNTs the turn-on electric field of AAO-CNTs
      increases from 4 V/microm to 6 V/microm as anodization voltage increase from 30
      to 40 V. Thus, anodization voltage of 30 V provides an optimal AAO-CNTs structure
      for electron field emission. The emission data have been analyzed based on the
      Fowler Nordhiem (F-N) model. AAO template prepared with 30 V anodization voltage
      is found to yield CNT nanoarray with optimum alignment and spacing that increase
      field enhancement factor by the lowering of field screening effect without
      significant lowering of CNTs density.

PMID- 22408994
TI  - Effect of electrodes on geometric and transport properties of the graphene-based
      nanomolecular devices.
AB  - Graphene-based nanomolecular devices are formed by connecting one of the
      prototype molecular materials of graphene nanoribbons to two Au electrodes. The
      geometric structure and electronic properties are calculated by using density
      functional theory. Basing on the optimized structure and the electronic
      distributions, we obtain the transport properties of the devices by using the
      Green's functional method. It is found that that the geometry structures of the
      molecule and the transport properties are sensitive to the distance between
      source and drain electrodes. With increasing the distances, the curvature radius
      of the atomic plane is increased, and the deformation energy is decreased. The
      current versus voltage curves have almost same threshold voltage with different
      distances between the electrodes. The transmission probability, the density of
      states and the external bias voltage play important role in determining the
      transport properties of the molecular devices.

PMID- 22408995
TI  - The model of nano-scale copper particle removal from silicon surface in high
      pressure CO2 + H2O and CO2 + H2O + IPA cleaning solutions.
AB  - This study focuses on the description of the static forces in CO2-H2O and CO2-H2O
      IPA cleaning solutions with a separate fluid phase entrapped between nano-scale
      copper particles and a silicon surface. Calculations demonstrate that increasing
      the pressure of the cleaning system decreases net adhesion force (NAF) between
      the particle and silicon. The NAF of a particle for in CO2-H2O-IPA system is less
      than that in CO2-H2O system, suggesting that the particles enter into bulk layer
      more easily as the CO2-H2O cleaning system is added IPA.

PMID- 22408996
TI  - Nucleation sequence of InAs quantum dots on cross-hatch patterns.
AB  - InAs quantum dots (QDs) are grown via molecular beam epitaxy on cross-hatch
      pattern (CHP) templates that result from lattice-mismatched epitaxy of In(x)Ga(1
      x)As on (100)-GaAs substrates. Growth of InAs on low-(x = 0.10) and medium-(x =
      0.13) mismatch CHPs with InAs thickness grading from sub- to beyond critical
      thickness show different stages of QD nucleation that is dictated mainly by
      surface steps. Tangential surface stress fields arising from the buried network
      of (110) misfit dislocations (MDs) at the InGaAs/GaAs interface are simulated in
      two dimensions and found to have a direct correlation to QD height at various
      locations, implying sequential QD nucleation at the surface intersection of the
      glide plane of dislocation T-section, cross-hatch intersection, threading
      dislocation, [1-10] MD line, and [110] MD line, followed by nucleation on the
      flat areas. Deviations from this nominal sequence is possible due to material
      anisotropy and are accounted for in the stress calculation by dislocation
      specific scaling factors.

PMID- 22408997
TI  - Anisotropic scattering of elongated GaSb/GaAs quantum dots embedded near two
      dimensional electron gas.
AB  - Geometrically anisotropic GaSb/GaAs quantum dots elongated along [110] direction,
      with a lateral aspect ratio of 2-3, are embedded in the vicinity of AIGaAs/GaAs
      two-dimensional electron gas, using the molecular beam epitaxy by carefully
      controlling the Sb4 beam flux and As4 background pressure. The electron
      mobilities micro parallel, micro perpendicular parallel and perpendicular to the
      direction of dot elongation axis are measured as functions of electron
      concentration n(2D) at 4.2 K, respectively. As the increase of n(2D), the
      mobility discrepancy (micro parallel-micro perpendicular) is found to be getting
      larger. This mobility difference is believed to be due to the anisotropic
      scattering potential of the elongated GaSb quantum dots. Under Born
      approximation, we propose a model with the constant squared-barrier potential to
      calculate the n(2D) dependence of mobility and reasonable agreement is achieved
      between the experimental results and theoretical simulation.

PMID- 22408998
TI  - Effect of annealing on magnetic properties of Ni80Fe20 permalloy nanoparticles
      prepared by polyol method.
AB  - Ni80Fe20 permalloy nanoparticles with narrow size distribution and homogeneous
      composition have been prepared by the polyol processing at 180 degrees C for 2 h
      and their particle sizes can be tunable in the size range of 20-440 nm by proper
      addition of K2PtCI4 agent. X-ray diffraction results show that the NiFe
      nanoparticles are of face centered cubic structure. The addition of K2PtCl4 does
      not affect the composition of NiFe NPs but decreases the particle size
      remarkably. Both saturation magnetization and coercivity of the as-prepared NiFe
      nanoparticles decrease with decreasing particle size. Annealed at 280 degrees C,
      however, the saturation magnetization of various sized NiFe nanoparticles
      increases drastically and approaches to the bulk for the -440 nm NiFe particles,
      and a maximum coercivity (-270 Oe) happens at a critical size of -50 nm. The
      magnetic property dependency of these NiFe nanoparticles on annealing has been
      discussed by considering the surface chemistry.

PMID- 22408999
TI  - TEM study and magnetic measurements of precipitates formed in Cu-Fe-Ni alloys.
AB  - The precipitation behavior of Cu-Fe alloys with Ni addition on isothermal
      annealing at 878 K was investigated by means of transmission electron microscopy
      (TEM), electron dispersive X-ray spectroscopy (EDS), and field-emission scanning
      electron microscopy (FE-SEM). Magnetic element atoms were segregated from the
      solid solution in supersaturated state, and nano-scale magnetic particles were
      randomly formed in the copper matrix at the initial stage of annealing at 873 K.
      With increasing the isothermal annealing time, however, the striking feature that
      two or more nano-scale magnetic particles with a cubic shape aligned linearly
      along (100) directions were observed upon the isothermal annealing at 873 K. To
      investigate the relationship between micro-structures and magnetic properties of
      the heterogeneous Cu-Fe-Ni alloys, magnetic measurements such as M-H measurements
      were also carried out, using a superconducting quantum interference device
      (SQUID) magnetometer. In this study, it was revealed that the magnetic properties
      of the specimen presented the ferromagnetic behavior, during the precipitation
      process in a Cu-Fe-Ni alloy.

PMID- 22409000
TI  - Optical and electrical properties of Ga-doped ZnO nanorod arrays fabricated by
      thermal evaporation.
AB  - Well-aligned Ga-doped ZnO nanorod arrays with high optical and electrical
      property were fabricated by catalyst-free thermal evaporation on p-silicon
      substrate. As the Ga/Zn atom ratio in the source material was tuned from 0 to
      0.2, wurtzite structure ZnO nanorod arrays were realized with length of -6 microm
      and growth direction along c-axis. With the addition of Ga, the intensity of the
      near-band-edge emission was enhanced and the deep-level emissions maintained
      neglectable. As the Ga/Zn atom ratio increased from 0 to 0.1, the red shift of
      the near-band-edge emission occurred due to Ga-doping induced band gap
      renormalization effect related with the enhancement of the carrier density, while
      the blue shifts of the emission were found once the Ga/Zn ratio is higher than
      0.1 resulting from Burstein-Moss effect. The configuration of the vertical
      aligned Ga-doped ZnO nanorod arrays on p-Si substrate makes it straightforward
      for the fabrication of p-n nanodiode, which shows an excellent rectifying
      characteristic with threshold voltage as low as -4.7 V with the Ga/Zn atomic
      ratio of 0.2.

PMID- 22409001
TI  - Analytic model of a silicon nanowire pH sensor.
AB  - A simple analytic model of a silicon-nanowire (Si-NW) pH sensor is proposed; this
      model is based on the solution of the Poisson equation in cylindrical coordinates
      and the nonlinear Poisson-Boltzmann equation for the Si-NW and an electrolyte,
      respectively. The simulation results obtained using the proposed model agree well
      with the experimental data. By using the proposed analytic model, the dependence
      of the electrical properties on the Si-NW diameter and doping concentration is
      investigated.

PMID- 22409002
TI  - Improved charge separation properties of organic hetero-junction solar cells by
      self-assembled monolayers anchored Ag nanoparticles.
AB  - We investigate the effect of self-assembled monolayers and localized surface
      plasmons of silver nano-particles on an organic solar cell consisting of zinc
      phthalocyanine as an active layer. The device was fabricated by covalent
      attachment of silver nanoparticles on n-type silicon substrates using self
      assembled monolayer of 4-mercaptophenol. Power conversion efficiency is increased
      up to 8 times as compared to a reference device with merely 0.13% photo
      conversion efficiency containing no self-assembled monolayers and silver nano
      particles. We believe that improved conductivity at the interface due to the
      aromatic self-assembled monolayer and the increased local electric field
      experienced by the active layer in presence of silver nano-particles act in
      synergy towards the higher population of excitons and dissipation of charge.

PMID- 22409003
TI  - Field emission from nanostructured AlN/GaN films on Si substrate prepared by
      pulsed laser deposition.
AB  - Nanostructured AIN/GaN films with different thickness are synthesized on Si
      substrates by pulsed laser deposition (PLD). GaN and AIN single-layer films are
      also deposited for comparison. It is found that the turn-on field of the
      nanostructured AIN/GaN films is considerably decreased 2 orders of magnitude than
      that of single-layer films. The improvement of field emission (FE)
      characteristics is attributed to the quantum structure effects, which supplies a
      favorable location of electron emission and enhances tunneling ability. We show
      that by tuning the thickness of AIN/GaN, various FE characteristics can be
      obtained. It indicates that the optimal thickness of the nanostructured AIN/GaN
      films exists for their best field emission performance.

PMID- 22409004
TI  - Polymer-assisted deposition of co-doped zinc oxide thin films for the detection
      of aromatic organic compounds.
AB  - Co-doped Zinc oxide thin films are deposited onto SiO2/Si substrate by polymer
      assisted deposition method. The surface morphology, structures and chemical
      states of the thin films are examined by scanning electron microscopy, X-ray
      diffraction, and X-ray photoelectron spectroscopy. The gas-sensing properties of
      the thin films upon exposure to aromatic organic compound vapors are also
      investigated. Co-doping is shown to be very effective in enhancing the response
      of ZnO thin film to aromatic organic compound.

PMID- 22409005
TI  - Fabrication and characterization of silicon quantum dots in Si-rich silicon
      carbide films.
AB  - Amorphous Si-rich silicon carbide films were prepared by magnetron co-sputtering
      and subsequently annealed at 900-1100 degrees C. After annealing at 1100 degrees
      C, this configuration of silicon quantum dots embedded in amorphous silicon
      carbide formed. X-ray photoelectron spectroscopy was used to study the chemical
      modulation of the films. The formation and orientation of silicon quantum dots
      were characterized by glancing angle X-ray diffraction, which shows that the
      ratio of silicon and carbon significantly influences the species of quantum dots.
      High-resolution transmission electron microscopy investigations directly
      demonstrated that the formation of silicon quantum dots is heavily dependent on
      the annealing temperatures and the ratio of silicon and carbide. Only the
      temperature of about 1100 degrees C is enough for the formation of high-density
      and small-size silicon quantum dots due to phase separation and thermal
      crystallization. Deconvolution of the first order Raman spectra shows the
      existence of a lower frequency peak in the range 500-505 cm(-1) corresponding to
      silicon quantum dots with different atom ratio of silicon and carbon.

PMID- 22409006
TI  - Synthesis and photoelectric properties of V3O7 x H2O and V3O7, nanobelts.
AB  - V3O7 x H2O nanobelts have been synthesized via a hydrothermal route. Monoclinic
      V3O7, nanobelts could be obtained by thermal decomposition of V3O7 x H2O
      nanobelts at 400 degrees C. The synthesized products were characterized by X-ray
      diffraction, scanning electron microscopy, and transmission electron microscopy.
      It was found that the V3O7 x H2O is of orthorhombic phase and single crystalline
      nanobelts with width of 100-500 nm and length up to 100 microm. The formation
      mechanism of the V3O7 x H2O nanobelts was discussed. Light sensitivity in
      exposure to a simulated sunlight in different intensity and biases have been
      investigated on the electrode made from the V3O7 x H2O and V3O7, nanobelts. The
      results show that the photocurrent intensity of the V3O7 nanobelts is much larger
      than that of the V3O7 x H2O nanobelts. The fast current response has been
      observed under alternative control of light on and off at 2 s interval.

PMID- 22409007
TI  - V2O5/polypyrrole core-shell nanotubes for gas sensor.
AB  - V2O5/polypyrrole core-shell nanotubes have been synthesized through an in situ
      polymerization of pyrrole monomers in the presence of prepared vanadium oxide
      nanotubes. Formation of polypyrrole in core-shell structure was endorsed by FTIR
      spectral analyses. Transmission electron microscopy images revealed that one
      dimensional morphology of vanadium oxide nanotubes remained undisturbed upon
      coating of polypyrrole, and polypyrrole was uniformly coated on the surface of
      vanadium oxide nanotubes, with a thickness of 30 nm. XRD suggested certain
      synergetic interaction existed in the core-shell structure, probably resulting in
      the enhanced thermal stability of polypyrrole coatings. The gas tests showed that
      the core-shell structure exhibited a high response, good stability and a short
      response/recovery time in the detection of different concentrations of ethanol at
      room temperature, implying its potential application for gas sensors. The
      enhanced gas sensing properties due to the synergic interaction between
      intimately contacted polypyrrole and vanadium oxide nanotubes lead to the
      formation of a hetero p-n junction with a depletion region, which is similar to a
      field effect transistor. The gas effects a change of the depletion region and
      thus modulates the conductivity of the junction.

PMID- 22409008
TI  - Stable aqueous dispersions of ZnO nanoparticles for ink-jet printed gas sensors.
AB  - For the preparation of printed devices based on ZnO nanoparticles (ZnO NPs),
      stable colloidal dispersions of these materials are highly desirable. ZnO NPs
      have been synthesized by Chemical Vapor Synthesis. The particles have a spherical
      shape with a narrow size distribution. Stable aqueous dispersions of the ZnO NPs
      have been successfully prepared after the addition of a polymeric stabilizer.
      These stable dispersions have been used to print ZnO NP films on interdigital
      gold structures on silicon by ink-jet printing. The printing parameters have been
      optimized for forming layers with high quality. Close-packed ZnO NP thin films
      with a thickness between 100-250 nm have been prepared. Impedance spectroscopy
      has been used to study the gas sensing properties of the printed films at
      different temperatures in air and in hydrogen. The impedance spectra show the
      semi-circles typical for semiconducting materials. The conductance of the printed
      films has been measured at room temperature with high accuracy. In hydrogen gas,
      the conductance is larger as expected and this behavior is reversible.

PMID- 22409009
TI  - Magnetic hollow mesoporous silica nanospheres: facile fabrication and ultrafast
      immobilization of enzymes.
AB  - Hollow mesoporous silica nanospheres with large pore size of around 11 nm have
      been synthesized by a structural difference based selective etching strategy, and
      the highly dispersed hydrophobic Fe3O4 nanoparticles with a particle size of 5 nm
      were then impregnated into hollow cores of nanospheres through these large pores
      by a vacuum impregnation technique. The structural characteristics of obtained
      magnetic composites were characterized by X-ray diffraction (XRD), Fourier
      Transform Infrared (FTIR), Transmission Electron Microscopy (TEM), Scanning
      Electron Microscopy (SEM), Selected Area Electron Diffraction (SAED), Ultraviolet
      visible (UV-Vis) and Vibrating Sample Magnetometer (VSM). The results show that
      the obtained Fe3O4-hollow mesoporous silica composites exhibit superparamagnetic
      property with saturation magnetization value of 4.17 emu/g. Furthermore, the
      obtained supports show ultrafast immobilization of hemoglobin and the immobilized
      enzymes are not denatured, indicating that the superparamagnetic hollow
      mesoporous silica spheres are excellent support for immobilization of enzymes
      with magnetic recycling property.

PMID- 22409010
TI  - Gas ionization sensors with carbon nanotube/nickel field emitters.
AB  - Gas ionization sensors based on the field emission properties of the carbon
      nanotube/nickel (CNT/Ni) field emitters were first developed in this work. It is
      found that the breakdown electric field (E(b)) slightly decreases from 2.2
      V/microm to 1.9 V/microm as the pressure of H2 gas increases from 0.5 Torr to 100
      Torr. On the contrary, E(b) obviously increases from 2.9 V/microm to 6.5 V/microm
      as O2 gas pressure increases from 0.5 Torr to 100 Torr. This may be explained by
      the depression of the electron emission that caused by the adsorption of the O2
      gas on the CNT emitters. The Raman spectra of the CNT/Ni emitters also show that
      more defects were generated on the CNTs after O2 gas sensing. The Joule heating
      effect under high current density as performing H2 sensing was also observed.
      These effects may contribute the pressure dependence on the breakdown electric
      field of the CNT/Ni gas ionization sensors.

PMID- 22409011
TI  - Investigation based on nano-electromechanical system double Si3N4 resonant beam
      pressure sensor.
AB  - This paper presents a type of NEMS (Nano-Electromechanical System) double Si3N4
      resonant beams pressure sensor. The mathematical models are established in
      allusion to the Si3N4 resonant beams and pressure sensitive diaphragm. The
      distribution state of stress has been analyzed theoretically based on the
      mathematical model of pressure sensitive diaphragm; from the analysis result, the
      position of the Si3N4 resonant beams above the pressure sensitive diaphragm was
      optimized and then the dominance observed after the double resonant beams are
      adopted is illustrated. From the analysis result, the position of the Si3N4
      resonant beams above the pressure sensitive diaphragm is optimized, illustrating
      advantages in the adoption of double resonant beams. The capability of the
      optimized sensor was generally analyzed using the ANSYS software of finite
      element analysis. The range of measured pressure is 0-400 Kpa, the coefficient of
      linearity correlation is 0.99346, and the sensitivity of the sensor is 498.24
      Hz/Kpa, higher than the traditional sensors. Finally the processing techniques of
      the sensor chip have been designed with sample being successfully processed.

PMID- 22409012
TI  - Microstructure and resistivity of machinable AIN/h-BN ceramic nanocomposites.
AB  - The microstructure and resistivity of AIN/BN ceramic nano-composites and micro
      composites were investigated. The results showed that because the nano-BN
      crystals were homogeneously dispersed around the AIN grains of the matrix, the
      conductive glass phase surround AIN grains were separated, and it was difficult
      to form the electric conductible consecutive passageway (than micro composites),
      the leakage conductance of nano-composites was far lower than micro-composites.

PMID- 22409013
TI  - Modified morphology of graphene sheets by Argon-atom bombardment: molecular
      dynamics simulations.
AB  - By a molecular dynamics method, we simulated the process of Argon-atom
      bombardment on a graphene sheet with 2720 carbon atoms. The results show that,
      the damage of the bombardment on the graphene sheet depends not only on the
      incident energy but also on the particle flux density of Argon atoms. To compare
      and analyze the effect of the incident energy and the particle flux density in
      the Argon-atom bombardment, we defined the impact factor on graphene sheet by
      calculating the broken-hole area. The results indicate that, there is an
      exponential accumulated-damage for the impact of both the incident energy and the
      particle flux density and there is a critical incident energy ranging from 20-30
      eV/atom in Argon-atom bombardment. Different configurations, such as sieve-like
      and circle-like graphene can be formed by controlling of different particle flux
      density as the incident energy is more than the critical value. Our results
      supply a feasible method on fabrication of porous graphene-based materials for
      gas-storages and molecular sieves, and it also helps to understand the damage
      mechanism of graphene-based electronic devices under high particle radiation.

PMID- 22409014
TI  - A facile approach to the synthesis of graphene nanosheets under ultra-low
      exfoliation temperature.
AB  - High specific surface area graphene nanosheets have been obtained from graphite
      oxide by using an effective modified exfoliation method under vacuum, the
      exfoliation temperature (135 degrees C) is much lower than that conventionally
      applied (1050 degrees C) to obtain monolayer graphene sheets via rapid thermal
      shock. These products have fluffy and highly porous structure and with a lateral
      size typically of a few micrometers. Transmission electron microscopy (TEM)
      observation shows that it looks like a wrinkled transparent ultrathin film
      consisting of single or few-layer graphene sheets, and their Brunauer-Emmett
      Teller surface area is as large as 750 m2/g. Simultaneously, X-ray photoelectron
      spectroscopy analysis revealed that considerable amount of oxygen-containing
      groups (C/O ratio, 5:1) retained on the graphene sheets after exfoliation
      process, which would provide convenience for further modification of the surface
      properties and chemistry of graphene sheets. This work offers a facile and
      scalable approach to fabricate graphene oxide and opens up a new vista of various
      potential applications electronics and composite materials.

PMID- 22409015
TI  - The device performance of Cu(In, Ga)Se2 solar cells influenced by the type
      inverted layer.
AB  - The type-inversion to n-type at the surface of p-type Culn(1-x)Ga(x)Se2 absorber
      layer is taken as an important factor for the high efficiency of Culn(1
      x)Ga(x)Se2 (CIGS) with low Ga content, however, the further increase of Ga
      content makes the n-type doping difficult and the type-inverted layer vanish,
      which may have a negative effect on the device performance. Previous first
      principles calculation had shown that the donor density becomes lower and level
      deeper when Ga content increases, while it's not clear how significantly the
      changes in the type-inverted layer influence the device performance. Through
      device simulation, we show that the efficiency decreases obviously as the donor
      density becomes lower and the level deeper in the inversion layer, thus they are
      important factors responsible for the limitation of the efficiency of CIGS solar
      cell, i.e., the efficiency decreases as Ga content exceeds 30%. Our work gives a
      good example in how to combine the electronic structure calculation of materials
      and device simulation to explain the experimental observation.

PMID- 22409016
TI  - Multi-resonant plasmonic transmission in a dual-periodically arranged metal
      insulator-metal waveguide.
AB  - A metallic heterowaveguide array, which is alternatively stacked by two kinds of
      metal-insulator-metal waveguides in a dual-periodic arrangement, has been
      investigated numerically. Based on the transfer matrix method and the principle
      of plasmon Bragg reflector, multi-resonant surface plasmon modes with high
      quality factors have been predicted in the structure. The number of the resonant
      modes, the corresponding center wavelengths as well as the mode intervals can be
      controlled flexibly by adjusting the structure parameters. Numerical simulations
      performed by the finite element method show good agreement with the predication
      of the transfer matrix method. Our results could be applied for the future
      surface-plasmon based wavelength division multiplexers at the telecommunication
      band, multi-channel filters, and multi-wavelength light-emitting diodes.

PMID- 22409017
TI  - Third-order optical nonlinearity of cadmium sulfide nanoparticles loaded in
      mesostructured silica materials.
AB  - Cadmium sulfide nanoparticles have been successfully incorporated in three forms
      of CTAB-templated mesoporous silica materials: one is the mesoporous silica
      spheres suspended in ethanol solution, the other is the mesoporous silica spheres
      spin-coated on glass slide, and the third is the dip-coated mesoporous silica
      thin film. The mesostructures were characterized by XRD and TEM, respectively.
      Linear optical properties were investigated using UV-visible spectra, and the
      diameter of the incorporated CdS nanoparticles was measured to be around 3.1 nm.
      Z-scan technique manifested that these three composites exhibited distinct third
      order optical nonlinearities due to the different preparation techniques. Reverse
      saturation absorption could be detected in the CdS-loaded mesoporous silica
      spheres suspended in solution, while those dispersed on glass slide presented
      saturation absorption. The difference in nonlinear absorption of the two
      mesoporous silica sphere samples could be attributed to defect-related
      transitions. On the contrary, the CdS-loaded mesoporous silica thin film showed
      self-defocusing behavior with no nonlinear absorption signals. Compared to that
      of the CdS nanoparticles with larger size previously reported, the intrinsic
      microscopic third-order nonlinear optical susceptibility of those incorporated in
      CTAB-templated mesoporous thin film was increased as predicted by the quantum
      theory, and the third-order optical nonlinearity was further determined to arise
      from intraband transitions induced by quantum confinement.

PMID- 22409018
TI  - Localized-surface-plasmon enhanced emission from porous silicon by gold
      nanoparticles.
AB  - The porous silicon (PS) samples, decorated by Au nanoparticles (NPs) possessing
      localized-surface-plasmon (LSP) resonance, are prepared by the conventional
      anodization method. Photoluminescence (PL) is studied systematically, in
      particular, its dependence on the excitation power. It is found that undecorated
      PS samples exhibit a saturation behavior in PL intensity with increasing the
      pumping laser power, while the luminescence of Au-decorated PS hybrid samples
      have a purely linear dependence on the excitation power. In the linear response
      region of PS samples, addition of metal NPs layer moderately suppresses the
      emission while, in the saturation region, the net emission is enhanced by
      approximately up to 4-fold. Several possible mechanisms are discussed. We believe
      that the observed PL enhancement in saturation region is dominantly due to the
      resonant coupling between the LSP of Au NPs and the electronic excitation of PS,
      which inhibits the nonradiative Auger recombination process at high excitation
      power. These results indicate that the plasmon effect could be useful for
      designing even more efficient optoelectronic devices such as super bright light
      emitting devices and solar cells with high efficiencies. Despite many challenges,
      Au NPs can potentially be applied to introduce LSP resonance for the future
      silicon-based optoelectronics or photonics.

PMID- 22409019
TI  - Functionalized bio-artifact fabricated via selective slurry extrusion. Part 1:
      Preparation of slurry containing tourmaline superfine powders.
AB  - The far infrared dental porcelain slurry for fabricating artificial tooth via
      selective slurry extrusion (SSE) of solid freeform fabrication (also known as
      rapid prototyping) techniques was prepared by using tourmaline as additive and
      employing ball-milling approach. After characterization by transmission electron
      microscopy, X-ray diffraction, and Fourier transform infrared spectrometry, it
      was found that the far infrared emission properties of the dental porcelain were
      apparently improved in the ranges of 2000-1201 cm(-1) and 881-600 cm(-1). This is
      due to the increase of the number of infrared active bonds that are from the
      tourmaline superfine powders. Moreover, it was also found that the tourmaline
      superfine powders can improve the pseudo-plastic properties of dental porcelain
      slurries, which results from the increase of the absolute value of zeta potential
      of the suspensions. Slurries with pseudo-plastic behavior are highly desirable in
      controlling the shape of the extrudate during solid freeform fabrication. With
      the functionalized material, a variety of bio-artifacts beneficial to body health
      can be built by using selective slurry extrusion machine.

PMID- 22409020
TI  - Decoration of carbon nanotube with SiO2 nanoparticles to improve polyelectrolyte
      membrane performance.
AB  - To overcome the poor mechanical performance and the low proton conductivity at
      high temperature (> 80 degrees C) which hinder the utilization of Nafion
      membranes for use in PEM Fuel Cell, SiO2 nanoparticle decorated multi-walled
      carbon nanotubes (MWCNTs) were developed to reinforce both the mechanical
      property and the water retention capability of Nafion membranes. Results show
      that the composite membrane is approximately 10% and 5-10% higher than that of
      recast Nafion membrane in proton conductivity and water retention, respectively.
      These could be explained by the bifunction of SiO2 which performs both
      hydrophilicity and proton conductivity. In addition, the mechanical performance
      was greatly enhanced in the presence of SiO2 decorated MWCNTs.

PMID- 22409021
TI  - The Coulomb interaction and volume compression effect on spin and orbital
      magnetic moment of NiO.
AB  - This calculation focuses on the effect of the Coulomb interaction U and the
      volume compression (VC) on both spin (m(s)) and orbital (m(o)) magnetic moment of
      NiO by using the local spin density approximation plus the Coulomb interaction
      (LSDA + U) method within full potential linear muffin-tin orbital (FP-LMTO). Our
      calculated results indicated that both spin and orbital magnetic moment strongly
      correlated to U and VC. The relevant results exhibited the increasing spin and
      orbital magnetic moments with increasing Coulomb interaction and decreasing
      volume compression. The interesting behavior appears when volume compression is
      greater than 70% at which m(s) collapses whereas m(o) linearly decreases. Further
      increase of volume compression to be at 80% leads to the disappearance of both
      magnetic moments. The present results exhibit the good correspondence to the
      experimental data at the normal pressure and U value of 6 eV.

PMID- 22409022
TI  - Photoluminescence and energy transfer study of Er3+ and Dy3+ codoped tellurite
      glasses.
AB  - Photoluminescence properties of the Er(3+)-Dy3+ codoped tellurite glasses were
      studied by absorption and visible emission spectra, which revealed luminescence
      bands of both Er3+ and Dy3+ when pumping with the wavelength of 325 nm. The
      concentration quenching occurred as Dy3+ concentration increased beyond 3 mol%.
      The dependence of Er3+ characteristic emission on Dy3+ concentration indicated
      energy transfer process between Er3+ and Dy3+. The chromaticity coordinates of
      these glasses are close to white light, which implies that these glasses might be
      potential candidates for white lighting through an appropriate combination.

PMID- 22409023
TI  - Ultraviolet-enhanced wettability and bioactivity of self-organized TiO2 nanotube
      layer.
AB  - TiO2 nanotube layers were prepared by anodic oxidation of commercial pure Ti in
      aqueous solutions containing 1 M (NH4)2SO4 and 0.15 M NH4F at 20 V for 2 h. The
      as-anodized layers were annealed at 450 degrees C for 3 h, and a part of the
      annealed layers were subsequently irradiated by Ultraviolet (UV) light in air for
      2 h at room temperature. Hydrophilicity and the apatite-forming ability of TiO2
      nanotube layers were evaluated. The results show that the as-anodized layer
      consists of self-organized TiO2 nanotubes with amorphous structure, which
      transforms to anatase after annealing at 450 degrees C for 3 h. The annealing
      treatment of the nanotube layer can significantly enhance its hydrophilicity and
      bioactivity. Furthermore, UV irradiation of the annealed TiO2 nanotube layer does
      not alter its surface morphology and phase component, however, can improve
      hydrophilicity and bioactivity. The enhanced hydrophilicity and bioactivity are
      thought to result from the abundant basic Ti-OH groups on the UV-irradiated TiO2
      nanotube layer.

PMID- 22409024
TI  - Formation and bioactivity of porous and nanostructured TiO2/beta-TCP coating on
      titanium.
AB  - Titanium and its alloys have been widely used as hard tissue implants due to
      their excellent mechanical properties and biocompatibility. However, their near
      bio-inertness and metallic ion release are still the problems with clinical uses.
      In this paper, porous and nanostructured TiO2/beta-tricalcium phosphate (beta
      TCP) composite coatings were prepared on titanium substrates by plasma
      electrolytic oxidation (PEO) in a Ca and P-containing electrolyte. The influence
      of PEO electric current density on phase composition and bioactivity of the
      coatings were studied. X-ray diffraction, scanning electron microscopy and
      Fourier transfer infrared spectroscopy were utilized to characterize the phase
      composition and microstructure of the coatings. Simulated body fluid immersion
      tests were employed on the coatings to evaluate their bioactivity. The results
      reveal that TiO2/beta-TCP composite coating with pores size less than 10 microm
      and grains of 50-100 nm in size was prepared. The electric current density of PEO
      is an important factor in the formation of the composite coating. The TiO2/beta
      TCP composite coating shows good bioactivity, which are attributed to the
      incorporation of beta-TCP.

PMID- 22409025
TI  - Study of novel self-alignment method for silicon nanowire.
AB  - A novel phenomenon on silicon nanowire (SiNW) is discussed here, which is related
      to its self-alignment characteristic when a temperature gradient field appears
      assisted by electric field. For the SiNW grown by vapor-liquid-solid method, it
      suffers an alignment force when its two terminals' temperature is different.
      Experiments about this effect have been observed and it has been anticipated that
      this property can be used in assembling SiNW array. Furthermore, some
      explanations on this effect have been made in this paper.

PMID- 22409026
TI  - Microstructure and crystallization kinetics analysis of the (In15Sb85)(100
      x)Zn(x) phase change recording thin films.
AB  - The (In15Sb85)(100-x)Zn(x) films (x = 0 - 17.4) were deposited on nature oxidized
      Si wafer and glass substrate at room temperature by magnetron co-sputtering of Sb
      target and InZn composite target. The thermal property of the films was examined
      by a homemade reflectivity thermal analyzer. Microstructures of the films were
      analyzed by transmission electron microscope (TEM). We examined the effects of Zn
      addition on the thermal property, crystallization kinetics, and crystallization
      mechanism of the In15Sb85 recording film. As x = 0 - 17.4, thermal analysis shows
      that the (In15Sb85)(100-x)Zn(x) films have two phase transition temperature
      ranges which are 189 degrees C-215 degrees C and 300 degrees C-350 degrees C. It
      is found that the activation energy is increased with Zn content. This indicates
      that the thermal stability of amorphous state is improved by doping Zn. The
      optical contrasts of the films are all larger than 15%, as x = 0 - 6.2,
      indicating that the films have the potential in blue laser optical recording
      media application.

PMID- 22409027
TI  - Toluidine red nanoparticles and their application in electrophoretic display.
AB  - Toluidine red pigment nanoparticles were prepared by anti-solvent precipitation
      and were modified by different surfactants aimed to use as the electrophoretic
      particles. Experimental conditions have been discussed in this paper including
      the effect of different surfactants, the concentration of surfactants, the
      reaction temperature and the agitation rate. Binary mixtures of organic solvents
      have been selected as suspending medium to improve the dispersion stability of
      the prepared particles. The produced nanoparticles have been characterized by
      scanning electron microscopy, laser diffractometer and electrophoretic display
      measuring system. The results indicated that the prepared particles modified by
      alkyl hydroxy oximido acid are in the average size of 80 nm with a spherical
      shape within narrow particle size distribution. The optimum content of AHOA,
      reaction temperature agitation rate are 3.75 g/L, 20 degrees C and 900 rpm,
      respectively. The prepared nanoparticles exhibit superior electrophoretic
      properties. Finally, the sedimentation of prepared particles dispersed into
      binary mixtures of tetrachloroethylene (C2Cl4) and cyclohexane is 4.76% for 2
      months.

PMID- 22409028
TI  - Preparation of gold nano-cones as surface-enhanced Raman scattering sensors for
      molecule detection.
AB  - Surface-enhanced Raman spectroscopy (SERS) is a powerful novel analytical tool
      which integrates high levels of sensitivity for trace analysis of chemical and
      biomolecular species due to the massive enhancement of Raman signals by using
      nanometre-sized metal particles. However, SERS can be envisaged as an analytical
      tool only if substrates with strong, predictable and reproducible SERS
      enhancement can be produced. Here we have developed one simple Ar+ ions
      sputtering technology to prepare gold nano-cones array on silicon substrates as
      surface-enhanced Raman scattering (SERS)-active substrates. The tip of the gold
      cone-structures exhibited an extremely sharp curvature with an apex diameter of
      20 nm and the interior apex angle of the nanocones was around 20 degrees. These
      samples were evaluated as potential SERS substrates using Rhodamine 6G molecules
      as molecule probe and exhibited SERS enhancement factor of greater than 10,
      originated from the localized electron field enhancement around the apex of cones
      and the surface plasmon coupling of periodic structures.

PMID- 22409029
TI  - Low-temperature fabrication of bunch-shaped ZnO nanowires using a sodium
      hydroxide aqueous solution.
AB  - Bunch-shaped ZnO nanowires film was successfully fabricated by the forced
      hydrolysis-initiated-nucleation of anhydrous zinc acetate in an aqueous solution
      of zinc acetate and sodium hydroxide at low temperature. X-ray diffraction and a
      field emission scanning electron microscope clarified their formation mechanism
      and morphology development. The morphology was controllable by adjusting the
      solution temperature and deposition time. ZnO nanowires obtained at 65 degrees C
      for 6 h have a high aspect ratio of about 106. The smaller diameter with higher
      aspect ratio of ZnO nanowires, the easier the formation of bunch shapes by the
      capillary force during the drying process. This fabrication technique indicated
      that bunched ZnO film was prepared at low cost, and fittable to low heat
      resistance substrates such as a polymer substarte.

PMID- 22409030
TI  - Microstructures and photoluminescence properties of three-dimensional multi
      layered ZnO flowers by surfactant-free hydrothermal method.
AB  - In this paper, a large-scale of three-dimensional multi-layered ZnO flowers
      constructed by porous nanosheets were fabricated on Zn foils through a surfactant
      free hydrothermal method. The morphology and microstructures of precursors and
      the mesoporous ZnO flowers were revealed by scanning electron microscopy. Based
      on the urea hydrolyzation, a possible growth mechanism of etching-deposition was
      proposed. The quantities and sizes of ZnO petals can be turned by urea
      concentration variations. The optical properties of the multi-layered ZnO flowers
      prepared with variety urea contents were also investigated by room temperature
      photoluminescence spectroscopy and showed the lower urea added sample has better
      crystalline quality.

PMID- 22409031
TI  - Fabrication of ferromagnetic nanoconstriction using atomic force microscopy
      nanoscratching.
AB  - Nanolithography used in conjunction with atomic force microscopy (AFM) has
      attracted considerable attention as a technique for fabricating nanoscale
      structures. To obtain nanostructures and devices, AFM nanoscratching was
      performed on a photoresist and on NiFe at various values of the applied force,
      scan speed, and number of scan cycles. The scratching process was carried out
      using a diamond-coated tip on NiFe and a Si tip on the photoresist. By conducting
      scratching processes on NiFe and on the photoresist, we investigated the
      dependence of the size of the scratched part on the scratching parameters. These
      results show that the width and depth of the scratched part increase as the
      applied force and number of scan cycles increase, but not as the scan speed
      increases. This means that it is possible to control the size of the scratched
      parts by adjusting the applied force and number of scan cycles. AFM
      nanoscratching was then used to directly fabricate a nanoconstricted area with a
      width of 139 nm and a cross-sectional area of less than 300 nm2 was fabricated.

PMID- 22409032
TI  - Enhanced wet etching of patterned GaN with ion implantation.
AB  - We present the enhanced wet etching of GaN epilayer implanted with Au+ ion.
      Patterned GaN with 2 microm-wide sink-like strips was achieved by using 500 keV
      Au+ ion implantation and KOH etching. The Dependence of etching depth on etching
      time for the implantation at different ion fluences was investigated. The
      experiment showed that the damaged GaN area could be almost etched out at high
      ion fluence, and the etching depth could exceed the project range of incident 500
      keV Au+ ion. The etch pits could be observed at the bottom of the etched area.
      The -400 nm depth etching could be achieved with high fluence implantation after
      a long etching time, and the edge of etched area could remain clear until the
      etching process had passed 40 min. As-deposited SiO2 spheres were used to mask
      the GaN sample in implantation process to investigate the etching effect. -70 nm
      wave of the GaN surface was observed. The results of our experiments may suggest
      an approach to the fabricating of GaN devices.

PMID- 22409033
TI  - Surface hardening of NiTi shape memory alloy induced by the nanostructured layer
      after surface mechanical attrition treatment.
AB  - To conduct grain refinement induced by plastic deformation, NiTi shape memory
      alloy is processed by surface mechanical attrition treatment. The process leads
      to surface nanocrystallization and consequently surface hardening. The cross
      sectional microhardness of the treated NiTi is measured and compared to those of
      annealed NiTi specimens with residual stress relaxation and recrystallization.
      Our results show that surface nanocrystallization induced by surface mechanical
      attrition treatment is an effective method to enhance the surface hardness and
      anti-wear properties of NiTi shape memory alloy for the biomedical application.

PMID- 22409034
TI  - Styrene-butadiene rubber/halloysite nanotubes composites modified by epoxidized
      natural rubber.
AB  - The reinforcement effects of halloysite nanotubes on styrene-butadiene rubber and
      the modification effect of epoxidized natural rubber on styrene-butadiene
      rubber/halloysite nanotubes composites were studied. The structure, morphology
      and properties of styrene-butadiene rubber/halloysite nanotubes composites before
      and after the incorporation of epoxidized natural rubber were investigated. The
      results indicated that epoxidized natural rubber can promote the dispersion and
      orientation of halloysite nanotubes in styrene-butadiene rubber matrix at
      nanoscale and strengthen interfacial combination between halloysite nanotubes and
      styrene-butadiene rubber by the formation of covalent bonds and hydrogen bonds
      between epoxidized natural rubber and halloysite nanotubes. Consequently
      epoxidized natural rubber can improve the mechanical properties of the
      vulcanizates of styrene-butadiene rubber/halloysite nanotubes composites. Besides
      epoxidized natural rubber can decrease the rolling resistance of the vulcanizates
      and increase the wet grip property of the vulcanizates.

PMID- 22409035
TI  - Synthesis of crystalline beta-FeSi2 under high-temperature and high-pressure.
AB  - In this paper, we report the synthesis of crystalline beta-FeSi2 via the reaction
      of Si and Fe powders under high-temperature and high-pressure. X-ray diffraction
      and Raman scattering results confirm formation of the beta-FeSi2 phase. Scanning
      electron microscopy, high-resolution transmission electron microscopy, and
      selected-area electron diffraction patterns show that the beta-FeSi2 phase
      coexists with Si phase with small nanocrystal sizes. The formation of the beta
      FeSi2 phase is a result of Si diffusion into Fe region. The obtained results
      suggest that the removal of Si phase can be reached through increasing Fe content
      and prolonging the duration of high-pressure thermal treatment.

PMID- 22409036
TI  - Influence of stacking fault energy on defect structures and microhardness of Cu
      and Cu alloys.
AB  - Nano-structured Cu, Cu-10 wt%Zn and Cu-2 wt%Al with stacking fault energies (SFE)
      of 78, 35 and 37 mJ/m2, respectively, were preprared through high energy ball
      milling. X-ray diffraction and Vickers microharness test were used to investigate
      the microstructure and microhardness of all the samples after ball milling. X-ray
      diffraction measurements indicate that lower SFEs lead both to decrease in grain
      size and increase in microstrain, dislocation and twin densities for Cu-10 wt%Zn
      and Cu-2 wt%Al after 5 h of ball milling. The microhardnesses of Cu-10 wt%Zn and
      Cu-2 wt%Al reach to nearly the same values of 2.5 GPa after 5 h of ball milling,
      which is higher than that of Cu of 2.0 GPa. Two factors are considered to
      contribute to the finer grian size and higher microhardness of Cu-10 wt%Zn and Cu
      2 wt%Al: (1) the effect of solid solution strengthening, which result in the
      interaction of solute atoms with screw dislocations; (2) the introduction of
      deformation twins during ball milling process by the decreasing of SFE, which
      results in the grain refinement.

PMID- 22409037
TI  - Nanostructured TiO2 films for dye-sensitized solar cells prepared by the sol-gel
      method.
AB  - TiO2 films were prepared on glass substrates using the sol-gel process for a dye
      sensitized solar cell application. The TiO2 sol was prepared using
      hydrolysis/polycondensation. Titanium (IV) Tetra Isopropoxide (TTIP) was used as
      precursor and Nitric acid (HNO3) was used as a catalyst for the peptization. The
      crystal structure and morphology of the prepared materials were characterized by
      XRD, and an SEM. The observations confirmed the nanocrystalline nature of the
      TiO2. The reaction parameters, such as the catalyst concentrations, the
      calcination time, and the calcination temperature were varied during the
      synthesis in order to achieve nanosize TiO2 particles. The prepared TiO2
      particles were coated onto FTO glass using a screen printing technique. The
      prepared TiO2 films were characterized by UV-vis. The TiO2 particles calcinated
      at low temperatures showed an anatase phase they grew into a rutile phase when
      the calcination temperature increased. The size and structure of the TiO2
      particles were adjusted to specific surface areas. It was found that the
      conversion efficiency of the DSSC was highly affected by the properties of the
      TiO2 particles.

PMID- 22409038
TI  - Photoconductive characteristic in individual WO(3-x) nanowire.
AB  - Tungsten Oxide nanowires, with their natural excellent structure, possess unique
      physical and chemical properties. In this paper, photoconductivity of single
      tungsten trioxide nanowire (WO3 NW) and single tungsten suboxide nanowire (WO(3
      x) NW) have been studied respectively on a photoconductivity testing system.
      Under 514 nm wavelength laser illumination, an unsaturated photocurrent and a
      slow photoconductive responsivity could be expressed in single WO3 NW device. In
      WO(3-x) NW device, photoconductive responsivity was determined by the
      illuminating position. About 100 nA photocurrent could be generated and a fast
      optoelectric responsivity with a recover time about 90 ms from the device was
      observed. Not only photoconductive effect but also the photovoltaic effect was
      obtained from individual WO(3-x) NW device. According to the results of X-ray
      photoelectron spectroscopy, the mechanisms of photoconductive and photovoltaic
      effects in these two kinds of devices have been discussed and the oxygen vacancy
      played an important role in the photoconductive phenomenon. All these effects
      could be of practical use in the design and fabrication of photodetectors based
      on single tungsten oxide nanowire.

PMID- 22409039
TI  - The near field properties of colloidal polystyrene microspheres on silicon.
AB  - We have investigated the optical resonance and near field inside and under
      absorptive polystyrene (PS) microspheres on Si wafers. Near field flat plane
      images of PS microspheres were numerically simulated. Nanostructures were
      prepared on Si substrates using the regular two dimensional (2D) arrays by a
      single pulsed laser irradiation (KrF, lambda = 248 nm). Periodical PS
      nanoparticle, PS nanoflowers and Si nanobumps were fabricated by different laser
      fluence. Mechanisms for PS particle size reduction and Si nanobump formation by
      laser irradiation were discussed on the base of the theoretical calculations.
      Good agreement between theoretical calculations and experimental results has been
      observed.

PMID- 22409040
TI  - Effect of ending surface on energy and Young's modulus of an armchair single
      walled carbon nanotubes.
AB  - The energy and Young's modulus as a function of tube length for (10, 10) armchair
      single-walled carbon nanotubes (SWCNTs) are investigated by using a linear
      scaling self-consistent-charge density functional tight binding (SCC-DFTB)
      method. It is found that the formula derived from total energy for a zigzag SWCNT
      [Physica B404, 3930 (2009)] can be also used to explain these calculated length
      dependent properties. Moreover, a transition occurs from fast change of length
      dependent properties of the SWCNT to their slow change. This transition
      corresponds to the SWCNT's length of about 5 nm. The length for the armchair
      SWCNT is about one half of that of the corresponding Zigzag SWCNTs. In addition,
      a definition of volume for a short SWCNT is discussed.

PMID- 22409041
TI  - Preparation of polymeric micelles consisting of poly(propylene glycol) and
      poly(caprolactone).
AB  - The ring-opening polymerization of epsilon-caprolactone (CL) was carried out with
      polypropylene glycol (PPG) as an initiator in the presence of the monomer
      activator HCl. Et2O to synthesize poly(epsilon-caprolactone)
      poly(propyleneglycol)-poly(epsilon-caprolactone) (PCL-PPG-PCL) triblock
      copolymers with change of length PPG and PCL. The micelle formation of PCL-PPG
      PCL triblock copolymers in an aqueous phase was confirmed by NMR, dynamic light
      scattering and fluorescence techniques. The critical micelle concentration (CMC)
      of the PCL-PPG-PCL triblock copolymers, determined from fluorescence
      measurements, was in range of 1.4 x 10(-3)-4.6 x 10(-3) mg/ml with dependence on
      block lengths of PPG and PCL. The partition equilibrium constant, K(v), which is
      an indicator of the hydrophobicity of the micelles of the PCL-PPG-PCL triblock
      copolymers in aqueous media, was also changed with dependence on length PPG and
      PCL. We confirmed that the PCL-PPG-PCL triblock copolymers formed micelles and
      hence may be potential hydrophobic drug carriers.

PMID- 22409042
TI  - Tissue distribution of intravenously administrated hydroxyapatite nanoparticles
      labeled with 125I.
AB  - Hydroxyapatite nanoparticles (HANPs) have been developed for biomedical use due
      to its extraordinary properties. However, the side effects of HANPs on human body
      have also been concerned, especially in vivo. Now it is still unknown how about
      the distribution and biobehavior of HANPs in vivo is, though it's very important
      for application in biosystem. This study was to establish a new method of 125I
      radiolabeling on HANPs at 80 nm, investigate the long-term tissue distribution of
      HANPs quantitatively after intravenously administrated HANPs labeled with 125I
      and the subcellular distribution in liver and spleen by TEM. The results
      indicated the labeled HANPs had high stability in vitro, and could accumulate
      mainly in the liver and spleen and decrease in time dependent manner, but still
      retain in body for more than 28 days. This stagnation most probably attribute to
      the endocytosis by macrophages in these tissues. The results implied the
      radioactive iodine labeling was an effective and sensitive method for tracing and
      analyzing the distribution of NPs in vivo. Liver and spleen should be the main
      target organ reached when HANPs were injected into circulation system. Because
      HANPs could stay in vivo for over one month, the biosafety shouldn't be
      neglected.

PMID- 22409043
TI  - Toxicity of carbon nanotubes to p21 and hus1 gene deficient mammalian cells.
AB  - Carbon nanotubes including single wall and multi wall carbon nanotubes (SWNT and
      MWNT) are attractive nanomaterials with great promise in industrial and medical
      applications. However, little is known about the role of p21 and hus1 gene in the
      toxic response of SWNT and MWNT to mammalian cells. The aim of this study is to
      investigate the role of the p21 and hus1 genes in the toxicity of carbon
      nanotubes. Comparison of micronucleus fraction between the wild type and p21 -/-
      , hus1 +/+ mouse embryo fibroblast (MEF) cells was performed experimentally. Our
      results show that the yield of the micronucleus ratio in p21 gene knock-out MEF
      cells is lower than that in the wild type counterpart, indicating that p21 may
      play as anti-apoptosis factor during the signal transduction of DNA damage caused
      by carbon nanotubes in mammalian cells.

PMID- 22409044
TI  - Simulation study on a new dual-material nanowire MOS surrounding-gate transistor.
AB  - In this paper, a novel field effect nanowire MOS transistor taking advantage of
      both dual-material gate and surrounding gate is proposed and performance
      characteristics are demonstrated numerically in detail. Surrounding-gate
      transistor is known to be used to enhance the electrostatic control of the
      channel, and dual-material-gate structure is extended from split-gate field
      effect transistor to obtain larger current and better short-channel performance.
      Three dimensional device simulations with Sentaurus Device are performed on this
      dual-material surrounding-gate transistor. Higher driving current, high ION/IOFF
      ratio and suppressed short-channel effects are obtained with this novel device
      structure.

PMID- 22409045
TI  - Direct growth of horizontally aligned carbon nanotubes between electrodes and its
      application to field-effect transistors.
AB  - This paper presents direct growth of horizontally-aligned carbon nanotubes (CNTs)
      between two predefined various inter-spacing up to tens of microns of electrodes
      (pads) and its use as CNT field-effect transistors (CNT-FETs). Using the
      conventional photolithography technique followed by thin film evaporation and
      lift off, the catalytic electrodes (pads) were prepared, consisting of Pt, Al and
      Fe triple layers on SiO2/Si substrate. The grown CNTs were horizontally-aligned
      across the catalytic electrodes on the modified gold image furnace hot stage
      (thermal CVD) at 800 degrees C by using an alcohol vapor as the carbon source.
      Scanning and transmission electron microcopies (SEM/TEM) were used to observe the
      structure, growth direction and density of CNTs, while Raman spectrum analysis
      was used to indicate the degree of amorphous impurity and diameter of CNTs. Both
      single- and multi-wall CNTs with diameters of 1.1-2.2 nm were obtained and the
      CNT density was controlled by thickness of Fe catalytic layer. Following
      horizontally-aligned growth of CNTs, the electrical properties of back-gate CNT
      FETs were measured and showd p-type conduction behaviors of FET.

PMID- 22409046
TI  - Nanotube substituted source/drain regions for carbon nanotube transistors for
      VLSI circuits.
AB  - Aggressive scaling of silicon technology over the years has pushed CMOS devices
      to their fundamental limits. Pioneering works on carbon nanotube during the last
      decade possessing exceptional electrical properties have provided an intriguing
      solution for high performance integrated circuits. So far, at best, carbon
      nanotubes have been considered only for the channel, with metal electrodes being
      used for source/drain. Here, alternative schemes of 'All-Nanotube' transistor are
      presented where even the transistor components are derived from carbon nanotubes
      which hold the promise for smaller, faster, denser and more power efficient
      electronics.

PMID- 22409047
TI  - Electron field emission characteristics of different surface morphologies of ZnO
      nanostructures coated on carbon nanotubes.
AB  - The optimal carbon nanotube (CNT) bundles with a hexagonal arrangement were
      synthesized using thermal chemical vapor deposition (TCVD). To enhance the
      electron field emission characteristics of the pristine CNTs, the zinc oxide
      (ZnO) nanostructures coated on CNT bundles using another TCVD technique.
      Transmission electron microscopy (TEM) images showed that the ZnO nanostructures
      were grown onto the CNT surface uniformly, and the surface morphology of ZnO
      nanostructures varied with the distance between the CNT bundle and the zinc
      acetate. The results of field emissions showed that the ZnO nanostructures grown
      onto the CNTs could improve the electron field emission characteristics. The
      enhancement of field emission characteristics was attributed to the increase of
      emission sites formed by the nanostructures of ZnO grown onto the CNT surface,
      and each ZnO nanostructure could be regarded as an individual field emission
      site. In addition, ZnO-coated CNT bundles exhibited a good emission uniformity
      and stable current density. These results demonstrated that ZnO-coated CNTs is a
      promising field emitter material.

PMID- 22409048
TI  - Preparation of SnO2 nanoparticles by hard template method for high selectivity
      gas sensors.
AB  - In this paper, SnO2 nanoparticles were synthesized by the impregnation method
      with SnCl2 x 2H2O as the inorganic precursor and mesoporous silica MCM-41 as the
      hard template. The physical and chemical properties of the products were
      characterized by X-ray diffraction (XRD) and transmission electron microscopy
      (TEM). The SnO2 nanoparticles grew into the ordered channels of MCM-41. After
      removing the silica template, the products exhibited good rutile structure. The
      gas sensing properties of the SnO2 nanoparticles were also studied. The results
      indicated that these SnO2 nanoparticle sensors showed high selectivity towards
      ethanol.

PMID- 22409049
TI  - Synthesis and self-assembly of ultrathin Ni(x)Fe(1-x)(OH)2 nanodiscs via a wet
      chemistry method.
AB  - Self-assembled ultrathin Ni(x)Fe(1-x)(OH)2 nanodiscs have been synthesized by
      using a wet-chemistry method. The uniformity and the assembly of Ni(x)Fe(1
      x)(OH)2 nanostructures are sensitive to the iron ion concentration in the
      precursor. An optimum iron concentration of 10% results in the formation of
      uniform ultrathin Ni(x)Fe(1-x)(OH)2 nanodiscs with a typical side length of 50 nm
      and a thickness of 10 nm. They are also self-assembled by connecting their (001)
      facets with in-plane orientation and form a chain-like microstructure. Lattice
      relaxation is present within several atomic layers at the interfaces between two
      adjacent nanodiscs, which introduces about 6 degrees misalignment of these
      nanocrystals. Analytical electron microscopy analysis reveals that the iron
      additive atoms distribute uniformly in the nanodiscs and they are substitution
      atoms of Ni atoms. It has been found that the iron species is critical to the
      formation and assembly of the hexagonal nanodiscs.

PMID- 22409050
TI  - Growth of metal-free carbon nanotubes on glass substrate with an amorphous carbon
      catalyst layer.
AB  - We have investigated the direct growth of metal-free carbon nanotubes (CNTs) on
      glass substrates with microwave-plasma enhanced chemical vapor deposition
      (MPECVD). Amorphous carbon (a-C) films were used as a catalyst layer to grow
      metal-free CNTs. The a-C films were deposited on Corning glass substrates using
      RF magnetron sputtering with the use of a carbon target (99.99%) at room
      temperature. They were pretreated with hydrogen plasma using a microwave PECVD at
      600 degrees C. Then, CNTs were prepared using microwave PECVD with a mixture of
      methane (CH4) and hydrogen (H2) gases. The CNTs were grown at different substrate
      temperatures (400 degrees C, 500 degrees C, and 600 degrees C) for 30 minutes.
      Other conditions were fixed. The growth trends of CNTs against substrate
      temperature were observed by field emission scanning electron microscopy (FE
      SEM). The structure of a-C catalyst layer and grown CNTs were measured by Raman
      spectroscopy. High-resolution transmission electron microscopy (HR-TEM) images
      showed that the CNTs had bamboo-like multi-walled structures. Energy dispersive
      spectroscopy (EDS) measurements confirmed that the CNTs consisted of only carbon.

PMID- 22409051
TI  - Fabrication and structure characterization of te butterfly nanostructures.
AB  - Te nanowires and butterfly nanostructures have been fabricated by template-free
      electrodeposition (TFED) in aqueous solution. By high-resolution transmission
      electron microscopy (HRTEM) study, the favored growth directions of the nanowires
      and the wings of the butterfly nanostructures were determined to be along the
      [0001] direction of trigonal Te, and the twinning plane of the butterfly
      nanostructures was (11-22). The cathodoluminescence measurements carried out at
      different positions of the butterfly nanostructure indicated that the twin
      boundaries influenced the photoemission efficiency.

PMID- 22409052
TI  - Estimation of AFM tip shape and status in linewidth and profile measurement.
AB  - An atomic force microscopy image is a dilation of the specimen surface with the
      probe tip. Tips wear or are damaged as they are used. And AFM tip shape and
      position status make AFM images distorted. So it is necessary to characterize AFM
      tip shape and position parameters so as to reconstruct AFM images. A geometric
      model-based approach is presented to estimate AFM tip shape and position status
      by AFM images of test specimens and scanning electron microscope (SEM) images of
      AFM tip. In this model, the AFM tip is characterized by using a dynamic cone
      model. The geometric relationship between AFM tip and the sample structure is
      revealed in linewidth and profile measurement. The method can easily calculate
      the tip parameters including half-cone angle, installation angle, scanning
      tilting angle and curvature radius, and easily estimate the position status of
      AFM tip when AFM tip moves on the specimen. The results of linewidth and profile
      measurement are amended accurately through this approach.

PMID- 22409053
TI  - Investigation of inner surface of silicon microchannels fabricated by
      electrochemical method.
AB  - Various silicon-based microchannels with different internal surface morphologies
      were investigated to improve the growth of carbon nanotubes on the inner surface
      of the pore wall. The morphology of the samples prepared under different
      conditions was characterized by scanning electron microscopy. Parameters such as
      concentration of hydrofluoric acid, potential, current density, temperature and
      so on were found to affect the inner surface of the pore wall. Experiments showed
      that certain etchant concentration, current density and temperature were
      important to the fabrication of samples with the regular structure and good
      morphology. By considering these factors, samples with the proper internal pore
      surface could be fabricated. Nickel was adopted as the metallic catalyst during
      electroless deposition onto the surface of the pore wall and bottom. The
      nickel/silicon microchannels were characterized and found to be suitable for the
      fabrication of carbon nanotubes by thermal chemical vapor deposition.

PMID- 22409054
TI  - Effect of annealing on the formation of p-type conductivity in nano
      Zn0.92Mn0.08O:N films.
AB  - P-type conductive Mn-N co-doped ZnO films were prepared by annealing N(+)
      implanted Zn0.92Mn0.08O films in a N2 ambient. Effect of the annealing on the
      structural, surface morphological, electrical and local chemical states of the
      films were investigated by X-ray diffraction (XRD), high-resolution field
      emission scanning electron microscopy (FE-SEM), Hall-effect and X-ray
      photoelectron spectroscopy (XPS) measurements, respectively. The results indicate
      that all the samples were single phase and well oriented along the c-axis. The as
      implanted samples were n-type semiconductors, while after thermal annealing at
      650 degrees C ranging from 10 to 30 minutes, they were converted to p-type
      conductivity with the hole concentration of 10(16)-10(17) cm(-3). But with
      further increasing the annealing time or the temperature, it was observed that
      the p-type conductivity decreased and ultimately reverted to n-type conductivity
      again. The change of conductive type may be ascribed to the local chemical states
      evolution of nitrogen in the process of thermal annealing.

PMID- 22409055
TI  - Tip-enhanced Rayleigh scattering and photoluminescence from semiconductor
      nanoparticles.
AB  - Tip-enhanced Rayleigh scattering images of Ge quantum dots grown on a Si
      substrate have been observed at room temperature. Changing the wavelength of the
      incidence light from 405 to 590 nm, the contrast of the images is reversed. It is
      found that the scattering intensity depends on the dielectric constants of the
      materials under the probe. By changing the wavelength of the incident light, we
      have obtained information about the dielectric constant dispersion of single Ge
      quantum dots. The spectral peak position of single Ge quantum dots is found to
      shift to higher energy, compared to that of bulk Ge. Tip-enhanced
      photoluminescence from an In0.25Ga0.75N film at room temperature has also been
      reported. The strong local enhancement of the photoluminescence of the localized
      excitons has been observed in the vicinity of a gold nano-particle attached to
      the end of the probe. A coupling to plasmons in the gold nano-particle yields
      strong enhancement of the photoluminescence.

PMID- 22409056
TI  - TiO2-based nano-wells for fabricating nanocrystals.
AB  - This paper reports a convenient bottom-up method to fabricate robust and inert
      TiO2-based nanowells for growing nanocrystals. These TiO2-based nanowells are
      fabricated in three steps: fabricating a thin film of self-organized TiO2
      nanotubes by the convenient electrochemical anodization method (Step 1), striping
      the fabricated nanotube thin film to expose the ordered array of nanowells
      underneath (Step 2), and surface modifying the exposed nanowells to adjust their
      surface hydrophobicity and hydrophilicity (Step 3). These fabricated nanowells
      can then be used to template the growth of an ordered array of nanocrystals by
      trapping a tiny droplet of precursor solution inside each nanowell. The diameter
      and surface hydrophobicity and hydrophilicity of the TiO2-based nanowells can be
      easily tailored by controlling the anodization parameters used in Step 1 and
      surface modifying parameters used in Step 3, respectively, thus enabling these
      TiO2-based nanowells a promising template substrate for growing a wide range of
      nanocrystals with adjustable sizes from aqueous and organic solvent systems.

PMID- 22409058
TI  - Synthesis and cellular biocompatibility of two nanophase hydroxyapatite with
      different Ca/P ratio.
AB  - The cellular biocompatibility of two types of nanophase hydroxyapatites including
      nanophase standard hydroxyapatite (n-HA) and nanophase calcium deficient
      hydroxyapatite (n-CDHA) synthesized by a wet chemical method were assessed using
      primary cultured osteoblasts. Cytotoxicity of both materials was investigated
      with L929 cell line. The MTT method was used to evaluate the proliferation of
      osteoblasts on the third day and ALP activity assay was carried out on the fifth
      day. SEM was used to observe the morphology of the osteoblasts on the third day.
      Two types of nanophase hydroxyapatite both showed no cytotoxicity. Higher cell
      proliferation was observed on n-CDHA than n-HA. At the same time, cells spread
      more actively on the n-CDHA group. The ALP level of n-CDHA was also significantly
      higher on the former. Our results show that the n-CDHA is more suitable for
      osteoblasts growth and is also helpful for ALP synthesis.

PMID- 22409057
TI  - Electrochemical behavior of gold nanoparticles modified nitrogen incorporated
      tetrahedral amorphous carbon and its application in glucose sensing.
AB  - Gold nanoparticles (NPs) with 10-50 nm in diameter were synthesized on nitrogen
      incorporated tetrahedral amorphous carbon (ta-C:N) thin film electrode by
      electrodeposition. The deposition and nucleation processes of Au on ta-C:N
      surface were investigated by cyclic voltammetry and chronoamperometry. The
      morphology of Au NPs was characterized by scanned electron microscopy. The
      electrochemical properties of Au NPs modified ta-C:N (ta-C:N/Au) electrode and
      its ability to sense glucose were investigated by voltammetric and amperometric
      measurements. The potentiostatic current-time transients showed a progressive
      nucleation process and diffusion growth of Au on the surface of ta-C:N film
      according to the Scharifker-Hills model. The Au NPs acted as microelectrodes
      improved the electron transfer and electrocatalytic oxidation of glucose on ta
      C:N electrode. The ta-C:N/Au electrode exhibited fast current response, a linear
      detection range of glucose from 0.5 to 25 mM and a detection limit of 120 microM,
      which hinted its potential application as a glucose biosensor.

PMID- 22409059
TI  - Binding studies of L-tryptophan to human serum albumin with nanogold-structured
      sensor by piezoelectric quartz crystal impedance analysis.
AB  - Nanogold-modified sensor was constructed and applied to study the binding of L
      tryptophan to human serum albumin (HSA) in situ by piezoelectric quartz crystal
      impedance (PQCI) analysis. It was interesting that the as-prepared nanogold
      modified sensor was more sensitive and biocompatible than bare gold electrode.
      The frequency changes due to protein adsorption on the nanogold-modified sensor
      might be described as a sum of two exponential functions and detailed explanation
      was given. Additionally, the kinetics of the binding process was also
      investigated. The binding constant (K) and the number of binding site (n) for the
      binding process without competitor are fitted to be 1.07 x 10(4) (mol l(-1))(-1)
      s(-1) and 1.13, respectively, and 2.24 x 10(3) (mol l-(1))(-1) s(-1) and 1.18,
      respectively for the binding process with competitor.

PMID- 22409060
TI  - Investigation on mechanism of growth arrest induced by iron oxide nanoparticles
      in PC12 cells.
AB  - Iron oxide nanoparticles (Fe3O4 NPs) have recently received increasing interest
      in the biotechnology and life science. However, little is known about the
      nanoneurotoxicity of Fe3O4 NPs following exposure to neurons. This study was to
      elucidate the cytotoxicity and DNA damage of Fe3O4 NPs on PC12 cells line which
      derived from Rattus norvegicus pheochromocytoma. The cell viability was observed
      by MTS assay and cell cycle status was analyzed using flow cytometry. DNA damage
      related gene (P53) and its downstream targets (P21 and GADD45) were determined by
      semiquantitative RT-PCR. The results showed that exposure to Fe3O4 NPs at dosage
      levels between 25 and 200 microg/ml decreased cell viability respectively. The
      nanoparticles treatment caused cell cycle arrest in G2/M phase and the mRNA
      levels of P53 increased when PC12 cells were incubated with different
      concentrations Fe3O4 NPs. However, P21 and GADD45, the downstream targets of P53,
      were not affected. In summary, exposure to Fe3O4 NPs resulted in a dose-dependent
      cytotoxicity in cultured PC12 cells that was associated with increased P53 gene
      expression and much attention should be paid to the potential impact of Fe3O4 NPs
      on the central nervous system.

PMID- 22409061
TI  - Electrochemical deposition of high density gold nanoparticles on indium/tin oxide
      electrode for fabrication of biosensors.
AB  - High density gold nanoparticles (GNPs) on indium tin oxide (ITO) film coated
      glass have been prepared by one-step electrochemical deposition from KAu(CN)2 in
      phosphate buffer (pH 8.0) solution. The resulting electrode surface was
      characterized by scanning electron microscopy (SEM), UV-vis spectroscopy, X-ray
      diffraction (XRD) and electrochemical method. Experimental results revealed that
      the number density of the nanoparticles was increased by the negative shift of
      the applied potential, while the coverage of the deposited GNPs on ITO substrate
      surface was also increased by means of the increasing deposition cycles. The
      presence of GNPs with high coverage improved the electrochemical response of
      Fe(CN)6 (3-/4-). This high coverage GNP/ITO substrate was applied to
      immobilization superoxide dismutase (SOD) for fabrication of electrochemical
      biosensors. The direct electron transfer between enzyme and electrode was
      realized, and the electrochemical performance of the SOD electrode was improved
      with the high coverage of GNPs. The biosensor exhibited a rapid and high response
      to superoxide anion.

PMID- 22409062
TI  - Superparamagnetic iron oxide nanoparticles for delivery of tissue plasminogen
      activator.
AB  - Magnetic nanoparticle (MNP) modified by carboxymethyl dextran (CMD) was
      synthesized and characterized by Fourier transform infrared spectroscopy,
      transmission electron microscopy, superconducting quantum interference device,
      dynamic light-scattering, thermogravimetric analysis, and X-ray diffraction. CMD
      coating on the particle surface provides abundant -COOH functional groups for
      conjugating with a thrombolytic drug, recombinant tissue plasminogen activator
      (rtPA). CMD-coated MNP (CMD-MNP) prepared with higher CMD/MNP ratios had higher
      CMD content, less iron content, more -COOH surface groups, smaller hydrodynamic
      diameter, and smaller saturation magnetization. The in vitro biocompatibility
      study using lactate dehydrogenase assays indicated that CMD-MNP elicited no cell
      cytotoxicity. The optimum drug loading could be achieved by contacting 0.25 mg
      rtPA with 5 mg CMD-MNP where all rtPA is immobilized to the magnetic nanocarrier
      with full retention of its thrombolytic activity.

PMID- 22409063
TI  - Determination of the transmission coefficients for quantum structures using FDTD
      method.
AB  - The purpose of this work is to develop a simple method to incorporate quantum
      effect in traditional finite-difference time-domain (FDTD) simulators. Witch
      could make it possible to co-simulate systems include quantum structures and
      traditional components. In this paper, tunneling transmission coefficient is
      calculated by solving time-domain Schrodinger equation with a developed FDTD
      technique, called FDTD-S method. To validate the feasibility of the method, a
      simple resonant tunneling diode (RTD) structure model has been simulated using
      the proposed method. The good agreement between the numerical and analytical
      results proves its accuracy. The effectness and accuracy of this approach makes
      it a potential method for analysis and design of hybrid systems includes quantum
      structures and traditional components.

PMID- 22409064
TI  - Formation of Cu or Cu2O nanoparticles embedded in a polyimide film for
      nanofloating gate memory.
AB  - Cu and Cu2O nanoparticles were fabricated in polyimide by curing the stacked
      polyamic acid/Cu/polyamic acid on Si wafer and post heat treatment. Nanoparticle
      distribution in polyimide (a monolayer of vertically aligned nanoparticles or the
      randomly dispersed nanoparticles) can be controlled by changing the reactivity of
      Cu with PAA and curing atmosphere. About 6-7 nm sized Cu or Cu2O nanoparticles
      were observed in the polyimide film. The capacitance-voltage curves were measured
      with Al/particles in polyimide/p-Si(100) specimens at 300 K, and the capacitance
      hystereses were observed at different sweep voltage ranges, which indicates that
      Cu2O or Cu nanoparticles can be utilized in next generation flash memories.

PMID- 22409065
TI  - Theoretical study on the peanut-shaped dimers and nanotubes consisted of C50
      cages.
AB  - The structures and electronic properties of the peanut-shaped dimers and
      nanotubes consisted of C50 cages are investigated based on the ab initio self
      consistent field molecular and crystal orbital calculations. It is found that the
      formation of peanut-shaped dimers is energeticlly favorable. The corresponding
      peanut-shaped nanotubes are semiconductors due to existence of the energy gaps.
      These peanut-shaped nanotubes are predicted to have smaller Young moduli than the
      single-walled carbon nanotube. The anionic peanut-shaped nanotubes are also
      calculated in this paper, as well as the infrared spectra of the peanut-shaped
      dimers.

PMID- 22409066
TI  - Preparation of nanorod-like anatase TiO2 nanocrystals and their photovoltaic
      properties.
AB  - Anatase TiO2 nanocrystals with the high specific surface area were prepared by
      the hydrothermal treatment of anatase TiO2 sols at the temperature of 150 degrees
      C and above. When TiO2 sols with a lower content of TiO2 and at a relatively high
      pH value were hydrothermal treated, the dispersible and nanorod-like TiO2
      nanocrystals were formed via the oriented attachment. The nanorod-like TiO2
      nanocrystals with an aspect ratio of larger than 5 and a mean diameter of less
      than 7 nm were obtained in the absence of organic compounds. The as-prepared TiO2
      nanocrystals were characterized with X-ray diffraction, transmission electron
      microscopy and BET surface area techniques. The TiO2 nanostructures were
      deposited on the FTO conductive glass as the anodic electrode for the dye
      sensitized solar cells (DSSCs) and assembled into solar cells. The derived solar
      cells showed a conversion efficiency of 6.12% under 1 sun illumination of
      simulated sunlight and external quantum efficiency (EQE) of more than 60% at the
      wavelength of 550 nm. The DSSCs from the anatase nanorods has a higher open
      circuit voltage compared to the spherical nanocrystals.

PMID- 22409067
TI  - Preparation of SnO2 nanowires by solvent-free method using mesoporous silica
      template and their gas sensitive properties.
AB  - In this paper, a facile method was presented to synthesize tin dioxide (SnO2)
      nanowires by solvent-free method using SnCl2 x 2H2O as precursor and mesoporous
      silica SBA-15 as the hard template. No solvent was used in the processing. The
      products were characterized by X-ray powder diffraction (XRD), transmission
      electron microscopy (TEM), energy dispersive spectroscopy (EDS) and N2
      adsorption/desorption isotherms. The results indicated that SnO2 nanowires
      fabricated by this method have a diameter of about 8 nm and a relatively high
      surface area 73.0 m2/g. The gas sensing properties of SnO2 nanowires were
      measured. The response and recovery time of this sensor were 6 s and 12 s,
      respectively. With the concentration of toluene increasing, the response of the
      sensor doubled increase. Compared with bulk SnO2, SnO2 nanowires showed much
      higher response to toluene.

PMID- 22409068
TI  - High frequency characteristics of Fe65Co35 alloy cluster-assembled films prepared
      by energetic cluster deposition.
AB  - Size-monodispersed Fe65Co35 alloy clusters whose average sizes ranged from 7 to
      12 nm were produced by a plasma-gas-condensation (PGC)-type cluster deposition
      apparatus. Fe65Co35 alloy cluster-assembled films were further prepared at room
      temperature by energetic cluster deposition method. Positively charged clusters
      in a cluster beam were accelerated electrically and deposited onto a negatively
      biased substrate together with neutral clusters from the same cluster source,
      leading to the formation of a high-density Fe65Co35 alloy cluster-assembled films
      with good soft magnetic properties. High frequency magnetic characteristics of
      these films were studied at room temperature using a high-frequency permeameter
      (RMF-3000, Ryowa). The real part (micro') of permeability for the Fe65Co35 alloy
      cluster-assembled films prepared at bias voltage V(a) = -20 kV has a large value
      of micro' = 135 at f = 1.5 GHz, and imaginary part (micro") of permeability has a
      maximum (micro" approximately 190) at about 2.5 GHz.

PMID- 22409069
TI  - A compact model for multi-island single electron transistors.
AB  - Multi-island single electron transistor is an important kind of the single
      electron transistor, which is convenient to realize the controllable room
      temperature operation. A novel semi-empirical compact model for the Multi-island
      single electron transistor is proposed. The new approach combines the orthodox
      theory of the single electron tunneling through single coulomb island and a novel
      empirical analysis procedure for the chain of multi coulomb islands to solve the
      current of the whole multi-island single electron transistor. The tunneling rates
      are calculated based on the orthodox theory for the single electron tunneling.
      The tunneling currents representing the first splitted peaks in the coulomb
      oscillation curves are calculated according to the assumption that the currents
      through all the coulomb islands are equal to each other at the stable states,
      while the currents representing the other splitted peaks are constructed and
      merged together according to the empirical analysis. The model is verified by the
      traditional SET simulator SIMON and shows much faster calculation speed than
      SIMON. Therefore, the novel compact model is suitable for the large scale MISET
      circuit simulation.

PMID- 22409070
TI  - Template-free synthesis and self-assembly of aligned nickel nanochains under
      magnetic fields.
AB  - Well-aligned and uniform Nickel nanochains with diameters ranging from 20 to 110
      nm have been synthesized using a simple template-free solution-phase method using
      environment friendly reagents under diverse temperature and magnetic field. Our
      results indicate that the size and morphology of as-prepared nanochains can be
      controlled by adjusting the reaction temperature and the applied magnetic fields,
      respectively. The formation of the aligned chains can be explained by the
      interactions of magnetic dipoles in the presence of magnetic field. Systematical
      magnetic measurements demonstrate that the saturation magnetization of the
      synthesized samples depends crucially on the particle size. Furthermore, the
      magnetic anisotropy of the well-aligned nickel nanochains is dominated by the
      shape anisotropy.

PMID- 22409071
TI  - Effects of Os inserted layers on the microstructures and magnetic properties of
      the FePt films.
AB  - The microstructure and magnetic properties of multilayer [Os(t)/FePt(x)]n films
      on a glass substrate with a 10 nm Os buffer layer by ion beam sputtering have
      been studied as a function of the annealing temperatures between 300 and 800
      degrees C. Here, t = 0.2, 1 or 5 nm and x varied from 10, 20, 25, 50, to 100 nm
      with its associated n value of 10, 5, 4, 2, and 1, respectively. No diffusion
      evidence was found in samples with a thin Os layer and t > or = 1 nm. The average
      grain size of the multilayer films can be well controlled by both annealing
      temperature and thickness of the FePt layer by a very thin Os space layer with t
      > or = 1 nm. The enhancement of H(c) can be understood from the fact that for a
      FePt film with an Os spacer layers, the increasing number of Os layer will
      inhibit the grain growth of FePt grains and enriches the grain boundary. We have
      experimentally demonstrated that even with a very thin 1 nm Os spacer layers, the
      [Os(t)/FePt(x)]n multilayer films can exhibit good hard magnetic properties and
      are attractive candidates for ultrahigh density magnetic recording media.

PMID- 22409072
TI  - Crystallization mechanisms of phase change (GeSbSn)(100-x)Co(x) optical recording
      films.
AB  - In this study, the (GeSbSn)(100-x0Co(x) films (x = 0-13.3) were deposited on
      natural oxidized silicon wafer and glass substrate by dc magnetron co-sputtering
      of GeSbSn and Co targets. The ZnS-SiO2 films were used as protective layers. The
      thicknesses of the (GeSbSn)(100-x)Co(x) films and protective layer were 100 nm
      and 30 nm, respectively. We investigated the effects of Co addition on the
      thermal property, crystallization kinetics, and crystallization mechanism of the
      GeSbSn recording film. The crystallization temperatures of (GeSbSn)(100-x)Co(x)
      films were decreased with Co content. It was found that the activation energy of
      the (GeSbSn)(100-x)Co(x) films will decrease from 1.53 eV to 0.55 eV as Co
      content increased from 0 at.% to 13.3 at.%.

PMID- 22409073
TI  - Synthesis and NO2-sensing properties of one-dimensional tungsten oxide nanowire
      bundles.
AB  - Tungsten oxide nanowires were synthesized by solvothermal method with tungsten
      hexachloride (WCl6) as precursor. X-ray diffraction, field emission scanning
      electron microscope and transmission electron microscope characterizations
      indicated that the as-synthesized nanowires are single phase monoclinic W18O49.
      With WCl6 concentration increasing, the bundled nanowire became shorter and
      thicker. The gas-sensing properties of W18O49 nanowire towards NO2 gas were
      evaluated and the results showed that the optimal gas sensitivity is achieved at
      150 degrees C and the thinner nanowire exhibits the higher sensitivity. The
      results indicate that tungsten oxide nanowire is a promising gas-sensing material
      for high performance and low power cost NO2 gas sensor.

PMID- 22409074
TI  - Fabrication and photoluminescence of Er(3+)-doped Al2O3 thin films with sol-gel
      method.
AB  - Erbium doped Al2O3 thin films were fabricated on quartz substrates in dip-coating
      process by sol-gel method, using the aluminum isopropoxide [Al(OC3H7)3]-derived
      AlOOH sols with the addition of erbium nitrate [Er(NO3)3 x 5H2O]. The as
      deposited films, which erbium concentration was between 20 and 43 mol%, were
      annealed in air from 600 to 1200 degrees C. The phase structure was detected by X
      ray diffraction (XRD) and the PL spectra in the wavelength range of 1400-1700 nm
      were investigated by spectrophotometer, which was exited by a 760 nm
      semiconductor LD. The PL spectrum shows a broadband extending from 1.430 to 1.670
      microm and centered at 1.55 microm, corresponding to the intra-4f transition
      between the first excited (4I(13/2)) and the ground state (4I(15/2)) of Er3+. The
      full width at half maximum (FWHM) of PL peaks increase from 60 to 100 nm with
      temperature increased from 600 to 1200 degrees C.

PMID- 22409075
TI  - Influence of substrates on the formation of the TiSi nanowire by atmosphere
      pressure chemical vapor deposition.
AB  - TiSi nanowires were deposited on both Si(111) and glass substrates by using SiH4,
      TiCl4 and N2 as the Si, Ti precursors and diluted gas respectively through
      atmosphere pressure chemical vapor deposition (APCVD) method. Effects of the
      substrates on formation of the nanowires were investigated. The results show that
      the nanowires can be formed on both Si(111) and glass substrates at ratio of
      SiH4/TiCl4 of 4. However, the quantities of the TiSi nanowires that formed with
      glass substrate are less than that with Si(111) substrate. The nanowires formed
      with glass substrate has length of 2-3 microm and diameters of 15-25 nm while
      that is 4-5 microm and 25-35 nm respectively with Si(111) substrate. Great
      quantities of the titanium silicide nanowires with relative higher contents of
      the C54 TiSi2 crystalline phase underneath can be obtained through improving the
      deposition conditions.

PMID- 22409076
TI  - Theoretical analyzing of monomers adsorbing in nano-slits.
AB  - A revised model based on Aranovich-Donohue Theory was built in this paper and was
      used to indicate the adsorbing behaviors of monomers in nano slits. This work
      tried to establish a theoretical model and get the fundamental mechanisms of the
      in situ-monomer-intercalation process which is the most common production method
      of polymer-layer silicate intercalated nanocomposite. According to the results,
      the multilevel adsorption and 3D phase transition phenomenon in nano slits
      predicted by Aranovich-Donohue Theory do not exit in reality. They are probably
      aroused by system errors caused by simple mean field approximation treatments.
      The nano slits have obvious boundary effects on density profile distribution of
      monomers. When the pore size increase, the density differences will be
      diminished. The adsorbing amounts will go up sharply in a narrow low-bulk
      concentration region and will decrease rapidly at most bulk-concentration-regions
      accompanied by the increasing of interaction energies of adsorbates. This should
      attribute to the capillary condensation phenomenon. The newly established model
      will be definitely helpful to reveal the fundamental mechanisms of in situ
      monomer-intercalation process for polymer-layer silicate intercalated
      nanocomposite.

PMID- 22409077
TI  - Preparation of layered inorganic/organic nanocomposites by nanosecond pulsed
      laser ablation of Ag in liquids.
AB  - A novel layered AgBr-based nanocomposite (designated as AgBr-NC) was prepared
      using nanosecond pulsed laser ablation in liquids (PLAL) in the presence of
      cetyltrimethylammonium bromide (CTAB). The obtained layered AgBr-NC possesses
      well-defined 2D shape. X-ray diffraction (XRD) pattern was composed of a series
      of peaks that could be indexed to (001) reflections of a layered structure, and
      the basal spacing of 20.0 angstroms indicated that the surfactant was included
      between the AgBr interlayers in an interdigitated bilayer arrangement. In this
      work, we provide an experimental proof for the synthesis of a novel layered two
      dimensional (2D) AgBr-NC nanosheet using PLAL in the presence of CTAB. The
      formation mechanism of 2D nanocomposites is also discussed.

PMID- 22409078
TI  - Polymer microspheres with active carboxyl groups: preparation, structure and
      hydrophilicity.
AB  - A quantitative research of microspheres, poly(ethylene glycol dimethacrylate-co
      acrylic acid) (P(EGDMA-co-AA)) and poly(divinvlbenzene-80-co-acrylic acid) (P(DVB
      co-AA)), with active carboxyl groups on surface prepared by distillation
      precipitation polymerization was presented in this paper. The loading capacity of
      active carboxyl group on microspheres which was investigated by titration
      technique would be increased and the contact angle was decreased following the
      increase of the feed ratio of acrylic acid (AA) monomer. This phenomenon
      indicated that the hydrophilicity of particles was mainly determined by the feed
      ration of hydrophilic AA monomer. However, when the AA fraction was at a fixed
      level, a slight difference of the loading capacity of carboxyl groups on
      microsphere surfaces with different crosslinkers existed. The microspheres with
      EGDMA as crosslinker had a higher loading capacity of carboxyl groups and lower
      contact angle than those of P(DVB-co-AA) microspheres, which indicated that
      P(EGDMA-co-AA) microspheres were more hydrophilic than P(DVB-co-AA) microspheres.

PMID- 22409079
TI  - Effect of Ag underlayer on microstructures and perpendicular magnetic properties
      of CoPt nanocomposite thin films.
AB  - CoPt/Ag films were prepared by magnetron sputtering on glass substrates and
      subsequent annealing. The dependence of degree of ordering and magnetic
      properties on Ag film thickness and annealing conditions were investigated. It
      was found that the Ag underlayer played a dominant role in inducing the (001)
      texture of the CoPt film after annealing. CoPt films with a thickness about 20 nm
      and Ag underlayers with a thickness about 70 nm are easy to obtain a large degree
      of ordering and a perpendicular magnetic anisotropy after annealing at 700
      degrees C for 30 min. CoPt/Ag films with out-of-plane coercivity (Hc
      (perpendicular)) in the range of 13.5-14.0 kOe and a out-of-plane squareness
      (S(perpendicular)) of 0.97 were obtained after annealing at 700 degrees C for 30
      min. Ag underlayer is beneficial to enhance the Hc(perpendicular)and
      S(perpendicular) of CoPt film significantly. The degree of ordering and
      perpendicular magnetic properties of the CoPt films which deposited on Ag
      underlayer are larger than those of the single layer CoPt films.

PMID- 22409080
TI  - Surface nanomechanical behavior of ZrN and ZrCN films deposited on NiTi shape
      memory alloy by magnetron sputtering.
AB  - Surface nanomechanical behavior under nanoindentation of ZrN and ZrCN film on
      NiTi substrate was studied. The surface hardness and modulus of the films
      increase initially with larger nanoindentation depths and then reach their
      maximum values. Afterwards, they diminish gradually and finally reaching plateau
      values which are the composite modulus and composite hardness derived from the
      ZrN/ZrCN film and NiTi substrate. They are higher than those of electropolished
      NiTi SMA due to the properties of ZrN and ZrCN. In comparison, the surface
      nanomechanical properties of electropolished NiTi exhibit a different change with
      depths.

PMID- 22409081
TI  - Facile synthesis of straight and branched CdTe nanowires using CdO as precursor.
AB  - High-quality colloidal CdTe nanowires (NWs) containing both straight and branched
      ones were controllably prepared via a solution-based approach, using a low
      melting Bi nanoparticles as catalysts, CdO and tributylphosphine telluride (TBP
      Te) as precursors, and a tri-n-octylphosphine oxide/tri-n-octylphosphine
      (TOPO/TOP) mixture as solvent. The resulting straight CdTe NWs have typical
      diameters below 20 nm accompanying with lengths exceeding 10 microm. In the case
      of branched CdTe NWs, tripod, V-shaped and y-shaped morphologies are obtained by
      decreasing the apparent Cd/Te molar ratio. It is found that, as the surface
      capping ligands, di-n-octylphosphinic acid (DOPA) is superior to decylphosphonic
      acid (DPA) in the reproducible growth of high-quality CdTe NWs. Since highly
      toxic dimethylcadmium, a cadmium precursor widely used in literatures, is
      replaced by CdO and the amount of the TOPO/TOP solvent mixture is significantly
      reduced, a relative safe and economical synthetic approach of high-quality
      colloidal CdTe NWs with controllable morphology is thus presented.

PMID- 22409082
TI  - Effects of potassium hydroxide post-treatments on the field-emission properties
      of thermal chemical vapor deposited carbon nanotubes.
AB  - In this study, a simple potassium hydroxide treatment was applied to
      functionalize the surface and to modify the structure of multi-walled carbon
      nanotubes grown on silicon substrates by thermal chemical vapor deposition.
      Scanning electron microscopy, transmission electron microscopy, Raman
      spectroscopy, and energy dispersive spectrometry were employed to investigate the
      mechanism causing the modified field-emission properties of carbon nanotubes.
      From our experimental data, the emitted currents of carbon nanotubes after
      potassium hydroxide treatment are enhanced by more than one order of magnitude
      compared with those of untreated carbon nanotubes. The emitted current density of
      carbon nanotubes increases from 0.44 mA/cm2 to 7.92 mA/cm2 after 30 minutes KOH
      treatment. This technique provides a simple, economical, and effective way to
      enhance the field-emission properties of carbon nanotubes.

PMID- 22409083
TI  - The growth of porous ZnO nanowires by thermal oxidation of ZnS nanowires.
AB  - The growth of porous ZnO nanowires (NWs) via phase transformation of ZnS NWs at
      500-850 degrees C in air was studied. The ZnS NWs were first synthesized by
      thermal evaporation of ZnS powder at 1100 degrees C in Ar. On subsequent
      annealing at 500 degrees C in air, discrete ZnO epilayers formed on the surface
      of ZnS NWs. At 600 degrees C, polycrystalline ZnO and the crack along the (0001)
      interface between the ZnO epilayer and ZnS NW were observed. At 700-750 degrees C
      ZnS NWs transformed to ZnO NWs, meanwhile nanopores and interfacial cracks were
      observed in the ZnO NWs. Two factors, the evaporation of SO2 and SO3 and the
      stress induced by the incompatible structure at the interface of ZnO epilayer and
      ZnS NW, can be responsible for the formation of porous ZnO NWs from ZnS NW
      templates on annealing at 700-750 degrees C in air. Rapid growth of ZnO at 850
      degrees C could heal the pores and cracks and thus resulted in the well
      crystallized ZnO NWs.

PMID- 22409084
TI  - Microwave-assisted synthesis and characterization of zinc oxide/carbon nanotube
      composites.
AB  - A composite material of zinc oxide and carbon nanotubes were successfully
      synthesized via a sol process using zinc acetate dihydrate and treated multi-wall
      carbon nanotubes under microwave irradiation. The morphology, microstructure and
      chemical bonding of as-obtained composites were well characterized using X-ray
      diffraction, scanning electron microscope, transmission electron microscope, and
      Fourier transform infrared spectroscopy. Zinc oxide nanoparticles were
      dispersively coated on the surface of carbon nanotube when the precursor was
      dried under microwave irradiation without post-annealing. X-ray diffraction
      results obviously showed the mixture of two phases of carbon nanotube and wurzite
      zinc oxide whose size is approximately 15 nm. The formation of zinc oxide
      nanoparticles on carbon nanotube surface in the composite prepared by microwave
      heating is much better than the composite heated by conventional annealing.
      Fourier transform infrared spectroscopic results suggest that carboxylic groups
      and uniform heating by microwave heating could play key roles on the nucleation
      of zinc oxide on carbon nanotube surface.

PMID- 22409085
TI  - Influence of structure parameters and crystalline phase on the photocatalytic
      activity of TiO2 nanotube arrays.
AB  - Titanium oxide nanotube arrays (TiO2-NTAs) with different diameters and lengths
      are prepared by anodization of titanium foils in a water/ethylene glycol solution
      (5:95 V/V) containing 0.3 wt% NH4F. The effects of the diameters, lengths and
      crystalline phases of the NTAs on the photocatalytic (PC) activity are
      systematically evaluated. Larger pore diameter results in higher PC activity. The
      PC activity increases initially and then decreases with lengths for TiO2-NTAs and
      the optimal length that yields the highest PC activity is observed to be 6.2
      microm. The crystalline phase and corresponding PC activity depend on the
      calcination temperature and their relationship is also investigated. The
      amorphous-to-anatase and anatase-to-rutile phase transitions initially occur at
      300 and 500 degrees C, respectively. The PC activity of TiO2-NTAs initially
      increases with calcination temperature from 250 to 500 degrees C and then
      decreases at higher calcination temperature. The enhanced PC activity observed
      from the samples annealed at 250-450 degrees C is attributed to the better
      anatase crystalline structure at higher calcination temperature. The highest PC
      activity with regard to photodecomposition of methyl orange is observed from TiO2
      NTAs calcined at 500 degrees C, which coincides with the anatse-to-rutile phase
      transformation. The synergistic effect of the anatase TiO2-NTAs and rutile
      barrier layers facilitate interfacial electron transfer consequently enhancing
      the PC activity. Further elevation of the calcination temperatures to 550 and 600
      degrees C exhibits diminished PC activity because the NTs become shorter due to
      conversion of the bottom of anatase NTs into rutile film.

PMID- 22409086
TI  - A comprehensive model of electrical noise in AlGaAs/GaAs long-wavelength quantum
      well infrared photodetectors.
AB  - We present the results of a comprehensive model for the electric noise simulation
      of a kind of nano-optoelectronics device: AIGaAs/GaAs long-wavelength quantum
      well infrared photodetectors (LW-QWIPs) in dark conditions by assuming a three
      dimensional carrier transport in the barriers where the electrical field are
      obtained in a self-consistent way. This model takes into account all the
      fundamental mechanisms involved in the device detection process. The electrical
      field distribution, dark currents, electrical noise are carefully calculated and
      analyzed. The numerical results also explain well our experimental observations.

PMID- 22409087
TI  - Photophysical and electrochemical properties of donor-acceptor conjugated
      oligomers based on 3,4-ethylenedioxythiophene and deficient rings.
AB  - The photophysical and electrochemical properties of four novel donor-accepter (D
      A) conjugated oligomers a-d based on 3,4-ethylenedioxythiophene (EDOT) and
      electrondeficient heterocycle rings were investigated. The UV-vis absorption
      spectroscopy, fluorescence emission spectroscopy and cyclic voltammertry studies
      suggest that the oligomers are expected to provide enhanced charge-transporting
      properties for the development of efficient electroluminescent materials.
      Furthermore, the third-order nonlinear optical (NLO) measurements made by Z-scan
      technique indicate that they have good third-order NLO response and are desired
      materias for fabricating nonlinear photonic devices. In the solid state of these
      oligomers, a strong tendency of self-assembled structure was also revealed by X
      ray diffraction (XRD) patterns in powder.

PMID- 22409088
TI  - Hydrogen dependent surface morphology study of plasma deposited SiN(x):H films
      for two gas systems SiH4/NH3 and SiH4/N2.
AB  - Partially amorphous silicon nitride thin films were deposited using plasma
      enhanced chemical vapor deposition technique using the two gas systems: SiH4/NH3
      and SiH4/N2. Fourier Transform infrared spectroscopy was employed to derive the
      relative changes in the bonded hydrogen content with increasing flow rates of NH3
      and N2. Surface morphology was monitored using atomic force microscopy. Root mean
      square surface roughness was found to be dependent on the NH3 and N2 flow rates,
      unlike silicon nitride films deposited by rf magnetron sputtering with variation
      in (N2/Ar) (Li et al. Thin Solid Films 334 (1998) 140). The discrepancy has been
      explained in the light of bonded hydrogen content in these films. The X-ray
      diffraction technique has also been used to observe the phases of the nitride
      films which showed the presence of silicon nitride grains oriented in (200),
      (400) and (221) directions in the predominantly amorphous as-deposited SiN(x):H
      films.

PMID- 22409089
TI  - Effect of micro/nano-scale rough surface on power dissipation of the waveguide:
      model and simulate.
AB  - A model and simulate research about the effect of roughness in micro/nano-scale
      on waveguide inner surface was presented in this paper. The roughness in
      micro/nano-scale of the waveguide was simulated by an improved two-dimensional
      fractal function to investigate its power dissipation. The numerical integration
      method and the finite element method were employed as well as two approximate
      formulas were deduced to calculate the power dissipation of the local and global
      roughness respectively. As verification, a simulation experiment by a rectangle
      waveguide was involved. The comparison of two-dimensional fractal and two
      classical models (rectangle and one-dimensional fractal) indicated that the
      result of the two-dimensional fractal model was more close to the test data in
      high working frequency. The surface density had little influence on power
      dissipation, while the influence of fractal dimension was very strong. Following
      the increase of surface roughness, the power dissipation of the rough surface
      increased and the maximum of the increase was 1.8 times than that of the smooth
      surface.

PMID- 22409090
TI  - Effect of strain on ferroelectric and magnetic behavior in Pb(Zr0.52Ti0.48)O3
      based magnetoelectric heterostructures.
AB  - In this paper, the "sandwich" structured magnetoelectric composite films of
      Pb(Zr0.52Ti0.48)O3/ NiFe2O4/Pb(Zr0.52Ti0.48)O3 and
      Pb(Zr0.52Ti0.48)O3/CoFe2O4/Pb(Zr0.52Ti0.48)O3 are epitaxially grown on
      SrRuO3/SrTiO3 substrates by pulsed-laser deposition. The crystalline quality and
      microstructures of these heterostructures are investigated by X-ray diffraction
      technique. The effects of strain on the ferroelectric, magnetic and
      magnetoelectric coupling properties of these thin films are systematically
      studied. The results show that the strain effect induced by lattice mismatch
      between the ferroelectric/ferromagnetic layers plays an important role in the
      ferroelectric and magnetic properties of these composite films. Compared to the
      strained Pb(Zr0.52Ti0.48)O3/ CoFe2O4/Pb(Zr0.52Ti0.48)O3 heterostructure, improved
      ferroelectric properties with an out-of-plane polarization (2P(r)) of 34.2
      microC/cm2 and electric coercivity field of 158 kV/cm are obtained in the strain
      free Pb(Zr0.52Ti0.48)O3/NiFe2O4/Pb(Zr0.52Ti0.48)O3 heterostructure. The ME
      measurement results not only show that the strain induced by lattice mismatch has
      great influence on the ME behavior, but also provide an understanding of the
      multilayers with full control over the interface structure at the atomic-scale.

PMID- 22409091
TI  - Executive function and medical non-adherence: a different perspective.
AB  - Medical non-adherence is multifactorial: cost, convenience, side effect profile,
      and cognitive impairment are all implicated in medical nonadherence. We explore
      impaired executive function (EF) as a cause for medical non-adherence when other
      causes can be ruled out. EF describes the coordination and manipulation of higher
      order cognitive processes involved in problem-solving, planning, and decision
      making. EF has three components: working memory, mental flexibility, and
      inhibitory control. The latter, inhibitory control, when impaired will affect an
      individual's ability to make choices to produce long-term benefits, in favor of
      short-term gratification. When applied to adults with chronic diseases, like
      diabetes, that require lifestyle modification and, at times, complicated medical
      regimens to forestall long term complications, an intact EF has a role in
      adherence. EF development is protracted with behavioral corollaries observable
      from early childhood. Thus, teachers, family physicians, and pediatricians will
      be the professionals to first encounter and manage such individuals. We suggest
      screening tests for children in the doctor's office to detect impaired EF, and
      postulate a cognitive behavioral therapeutic approach for adults with
      uncontrolled DM and impaired EF.

PMID- 22409092
TI  - Cytokine levels as potential biomarkers for predicting the development of
      posttraumatic stress symptoms in casualties of accidents.
AB  - BACKGROUND: Traumatic injuries are usually associated with increased secretion of
      pro-inflammatory cytokines, and are sometimes followed by the development of
      acute stress symptoms (ASS) and posttraumatic stress symptoms (PTSS). AIMS: To
      measure serum pro- and anti-inflammatory cytokines in accident casualties and to
      associate it with ASS at hospitalization, and with PTSS 1 month later. METHODS:
      Participants were 48 patients, aged 20-60, hospitalized following various
      orthopedic injuries including bone fractures, and 13 healthy volunteers matched
      for gender. At hospitalization (Time 1), 30 ml heparinized venous blood were
      drawn and cytokines levels in serum were assessed; participants filled out the
      Acute Stress Disorder Inventory (ASDI), COPE, and injury-related questionnaires.
      One month later (Time 2), 26 participants filled out the Posttraumatic Disorder
      Symptom Scale (PDS). RESULTS: High serum levels of IL-6, IL-8, and TGF-beta and
      low levels of serum IL-4 and IL-10 were found in injured patients as compared
      with controls, When controlling for age and severity of injury in the regression
      analysis, higher levels of IL-6 and IL-8 and lower TGF-beta were predicted by
      higher ASS and higher use of and emotion-focused coping. Higher PTSS scores at
      Time 2 were predicted by higher levels of IL-8, lower levels of TGF-beta, and
      higher ASS measured at Time 1. CONCLUSIONS: High levels of the pro-inflammatory
      cytokine IL-6 and IL-8 and lower levels of the regulatory cytokine TGF-beta
      should be further assessed as a possible risk factor or a bio-marker of PTSS in
      accident casualties.

PMID- 22409093
TI  - What do primary care doctors get out of a year-long postgraduate course in
      community psychological medicine?
AB  - OBJECTIVE: There are increasing expectations on primary care doctors to care for
      patients with common mental health problems. This study examines the outcomes of
      a postgraduate training course in psychological medicine for primary care
      doctors. METHODS: A questionnaire developed by the research team was sent to the
      Course graduates (year 2003-2007). A retrospective design was adopted to compare
      their clinical practice characteristics before and after the Course. Differences
      in the ratings by the respondents before and after the Course were analyzed using
      the nonparametric Wilcoxon signed rank test. RESULTS: Sixty-nine graduates
      replied with a response rate of 58.5% (69/118). Most respondents were confident
      of diagnosing (96.9%) and managing (97.0%) common mental health problems after
      the Course, compared to 50.0% and 50.7%, respectively, before the Course. Most
      graduates had modified their approach, increased their attention and empathy to
      patients with mental health problems. The percentage of respondents having enough
      time to treat these patients had increased from 55.8% to 72.1%. The median number
      of patients with mental health problems seen per week was in the range of 3-6
      before, and had increased to the range of 7-10 after the Course. The proportion
      of respondents being confident of making appropriate referrals had increased from
      72.8% to 97.0%, while the number of referrals to psychiatrists had dropped
      significantly. CONCLUSIONS: The Course is effective in improving graduates'
      confidence, attitude, and skills in treating patients with common mental health
      problems. There are significant increases in the number of mental health patients
      handled, increased confidence in making referrals to psychiatrists, and decreased
      percentage of patients being referred.

PMID- 22409094
TI  - The effects of a psychoneuroimmunology (PNI) based lifestyle intervention in
      modifying the progression of depression in clinically depressed adults.
AB  - OBJECTIVE: Uncontrolled stress can lead to poorly controlled upsurges of cortisol
      and deregulation of the hypothalamus pituitary-adrenal axis (HPA), thereby
      leading to major depression. Psychoneuroimmunology (PNI) is the area of medicine
      dealing with the bidirectional pathways connecting the influences of brain,
      neuroendocrine, and immune system. Individual PNI-based lifestyle interventions
      such as humor and guided imagery have been shown to modulate the stress response.
      However, researchers have not examined the composite effect of a PNI-based
      lifestyle intervention among clinically depressed adults. METHOD: This randomized
      interventional study examined the composite effect(s) of a PNI-based lifestyle
      intervention: progressive muscle relaxation, spiritual guided imagery, and humor
      as an adjunct therapy to modifying the progression of depression. Forty-one
      participants recruited from doctors' offices in San Bernardino and Riverside
      counties in Southern California, were randomized into two groups: treatment (N =
      20) and control (N = 21). For a period of three weeks, participants in the
      treatment group listened to a 12-minute progressive muscle relaxation and
      spiritual guided imagery CD daily and watched 10 minutes of humorous DVDs.
      Participants in both groups were also receiving cognitive behavioral therapy and
      pharmacotherapy. RESULTS: Depression, spirituality, humor, and stress were
      assessed at baseline and week 3. Depression significantly decreased from severe
      to mild from baseline to week 3 in the treatment group. Spirituality
      significantly increased in the treatment group but remained unchanged in the
      controls. CONCLUSIONS: These findings offer depressed patients alternative
      approaches to preventing complications and managing their illness in the context
      of whole-person lifestyle optimization and integration of mind-body-spirit.

PMID- 22409095
TI  - A comparison of the acute stress reactions between the Han and Tibetan ethnic
      groups in responding to devastating earthquakes.
AB  - OBJECTIVE: The purpose of the present study was to investigate whether there were
      differences in the acute stress reaction (ASR) between the Tibetan and the Han
      ethnic groups after experiencing devastating earthquakes. METHODS: One hundred
      twelve Han survivors of the Wenchuan earthquake and 112 Tibetan survivors of the
      Yushu earthquake were rated using the PTSD Checklist-Civilian (PCL-C) according
      to their trauma experiences, ages, genders, severity levels of injuries, and
      medical services received. RESULTS: Injured Tibetans had lower scores across
      symptom clusters of avoidance, numbing, and the total score of PCL-C as compared
      to Hans. Among Tibetans, severe ASR was associated with a higher education level
      and earthquake experience, whereas only earthquake experience was associated with
      severe ASR among injured Hans. CONCLUSION: Cultural factors may play significant
      roles in the acute stress reaction of survivors with different cultural
      backgrounds following an earthquake.

PMID- 22409096
TI  - Dipping status and hostility in newly diagnosed essential hypertension.
AB  - AIM: Personality traits, including hostility, play an important role in the
      development of cardiovascular disease. Moreover, abnormalities in blood pressure
      circadian pattern, such as a lack of nocturnal BP fall, are related with target
      organ damage and increased cardiovascular risk. The aim of this study was to
      investigate the impact of hostility and its dimensions on dipping status, in
      newly diagnosed hypertensive patients. METHODS: The study population consisted of
      114 newly diagnosed untreated essential hypertensives. All participants underwent
      24-hour ambulatory blood pressure monitoring (ABPM) in order to assess dipping
      status. Hostility was assessed by Hostility and Direction of Hostility
      Questionnaire (HDHQ). The study population was divided in terms of dipping status
      in two groups, "dippers" and "non-dippers." RESULTS: The statistical analysis
      revealed that dippers presented significantly higher score of extrapunitiveness
      (13.2 +/- 4.9 vs 11.4 +/- 3.9, p = 0.032), as well as significantly higher score
      of the dimension "urge to act out hostility (AH)" (4 +/- 3 vs 3 +/- 2, p = 0.025)
      compared to non-dippers. Multivariate regression analysis revealed
      extrapunitiveness as the only independent predictor of dipping status. The odds
      ratio (OR) for dipping status associated with each point increase in
      extrapunitiveness was 0.912 (95% CI: 0.832-0.992; p = 0.048). CONCLUSION: The
      present findings may suggest that hostility and its features affect the circadian
      variation of blood pressure in hypertensive patients, providing a promising
      objective for future investigations linking psychological factors and dipping
      status in essential hypertension.

PMID- 22409097
TI  - Identifying symptom profiles of depression and anxiety in patients with an acute
      coronary syndrome using latent class and latent transition analysis.
AB  - OBJECTIVE: To identify symptom profiles of depression and anxiety in patients
      with an acute coronary syndrome (ACS), to examine changes in symptom profiles
      over time, and finally, to examine the effects of age and sex on patients'
      symptom profiles. METHODS: One hundred ACS patients with mild to severe symptoms
      of depression and/or anxiety at 1 month post-hospital discharge were enrolled in
      a randomized trial of cognitive behavioral therapy. Latent class and latent
      transition analyses were used to identify symptom profiles and describe change
      over the time in profile membership. RESULTS: A two-class solution was selected
      to describe depression and anxiety symptom profiles. Class I (76% of patients at
      baseline) was labeled "depression and some anxiety symptoms." Class II (24% of
      patients at baseline) was labeled "anxiety and some depression symptoms."
      Approximately 25% of patients in the treatment condition transitioned from the
      depression and some anxiety symptoms class to the anxiety and some depression
      symptoms class at follow-up compared to 10% of patients in the control condition
      at follow-up; nearly 50% of patients in the control condition showed worsening of
      symptoms as compared to 28% in the treatment condition. Results suggested age
      differences in the probabilities of transitioning between the classes; older
      patients were more likely to continue having depression and some anxiety symptoms
      at the time of follow-up. CONCLUSIONS: Identifying symptom profiles of depression
      and anxiety in patients with an ACS may improve diagnostic practices and help to
      design tailored interventions.

PMID- 22409098
TI  - Early heelstrike kinetics are indicative of slip potential during walking over a
      contaminated surface.
AB  - OBJECTIVE: The objective of this study is to examine ground kinetics early in
      stance while walking on a contaminated surface and assess the potential of
      kinetics to quantify risk of slipping. BACKGROUND: Prior studies of slipping have
      dismissed early ground kinetic data,and therefore no prior literature has been
      able to assess the viability of using these data to quantify slip potential.
      METHOD: A total of 11 healthy male participants volunteered to walk over a force
      plate that was at random times contaminated with soap.Ground kinetics were
      measured by the force plate (2400 Hz), and heel displacement was quantified using
      high-speed video cameras (240 Hz) and retro-reflective markers. RESULTS: The
      results indicated a significant reduction in shear force as early as 0.42 ms
      after heelstrike for contaminated trials, whereas for utilized coefficient of
      friction, a significant reduction was not seen until 11.34 ms. Heel displacements
      considered "safe" in the literature (< 30 mm) demonstrated proportionally
      different thresholds for shear force and utilized coefficient of friction.
      CONCLUSION: The authors suggest that shear force in early stance shows more
      promise in quantifying slip potential as compared to utilized coefficient of
      friction given that (a) significant differences are seen earlier in shear than
      utilized coefficient of friction and (b) the threshold for utilized coefficient
      of friction, over which heel displacement stabilized to a"safe" value, exceeded
      values for utilized coefficient of friction that have been recommended as "safe".
      APPLICATION: These results have wide implications for standards related to the
      design and testing of interventions to prevent injuries because of slipping.

PMID- 22409099
TI  - Low conspicuity of motorcycles for car drivers: dominant role of bottom-up
      control of visual attention or deficit of top-down control?
AB  - OBJECTIVE: The aim of this study was to evaluate whether the low visibility of
      motorcycles is the result of their low cognitive conspicuity and/or their low
      sensory conspicuity for car drivers. BACKGROUND: In several cases of collision
      between a car and a motorcycle, the car driver failed to detect the motorcyclist
      in time to avoid the collision. METHOD: To test the low cognitive conspicuity
      hypothesis, 42 car drivers (32.02 years old) including 21 motorcyclist motorists
      and 21 non-motorcyclist motorists carried out a motorcycle detection task in a
      car-driving simulator.To test the low sensory conspicuity hypothesis, the authors
      studied the effect of the color contrast between motorcycles and the road surface
      on the ability of car drivers to detect motorcycles when they appear from
      different parts of the road. RESULTS: A high level of color contrast enhanced the
      visibility of motorcycles when they appeared in front of the participants.
      Moreover, when motorcyclists appeared from behind the participants,the
      motorcyclist motorists detected oncoming motorcycles at a greater distance than
      did the non-motorcyclist motorists. Motorcyclist motorists carry out more
      saccades and rapidly capture information (on their rearview mirrors and on the
      road in front of them). CONCLUSION: The results related to the sensory
      conspicuity and cognitive conspicuity of motorcycles for car drivers are
      discussed from the viewpoint of visual attention theories. APPLICATION: The
      practical implications of these results and future lines of research related to
      training methods for car drivers are considered.

PMID- 22409100
TI  - Individual differences in the benefits of feedback for learning.
AB  - OBJECTIVE: Research on learning from feedback has produced ambiguous guidelines
      for feedback design--some have advocated minimal feedback, whereas others have
      recommended more extensive feedback that highly supported performance. The
      objective of the current study was to investigate how individual differences in
      cognitive resources may predict feedback requirements and resolve previous
      conflicted findings. METHOD: Cognitive resources were controlled for by comparing
      samples from populations with known differences, older and younger adults.To
      control for task demands, a simple rule-based learning task was created in which
      participants learned to identify fake Windows pop-ups. Pop-ups were divided into
      two categories--those that required fluid ability to identify and those that
      could be identified using crystallized intelligence. RESULTS: In general, results
      showed participants given higher feedback learned more. However, when analyzed by
      type of task demand, younger adults performed comparably with both levels of
      feedback for both cues whereas older adults benefited from increased feedbackfor
      fluid ability cues but from decreased feedback for crystallized ability cues.
      CONCLUSION: One explanation for the current findings is feedback requirements are
      connected to the cognitive abilities of the learner-those with higher abilities
      for the type of demands imposed by the task are likely to benefit from reduced
      feedback. APPLICATION: We suggest the following considerations for feedback
      design: Incorporate learner characteristics and task demands when designing
      learning support via feedback.

PMID- 22409101
TI  - Conceptualization and measurement of team workload: a critical need.
AB  - OBJECTIVE: The purpose of this article is to present and expand on current
      theories and measurement techniques for assessing team workload. BACKGROUND: To
      date, little research has been conducted on the workload experienced by teams. A
      validated theory describing team workload, which includes an account of its
      relation to individual workload, has not been articulated. METHOD: The authors
      review several theoretical approaches to team workload.Within the team research
      literature, attempts to evaluate team workload have typically relied on measures
      of individual workload. This assumes that such measures retain their validity at
      the team level of measurement, but empirical research suggests that this method
      may lack sensitivity to the drivers of team workload. RESULTS: On the basis of
      these reviews, the authors advance suggestions concerning a comprehensive theory
      of team workload and methods for assessing it in team settings. The approaches
      reviewed include subjective, performance, physiological, and strategy shift
      measures. Theoretical and statistical difficulties associated with aggregating
      individual-level workload responses to a team-level measure are discussed.
      CONCLUSION: Conception and measurement of team workload have not significantly
      matured alongside developments in individual workload. APPLICATION: Team workload
      remains a complex research area without simple measurement solutions, but as a
      research domain it remains open for contributions from interested and
      enterprising researchers.

PMID- 22409102
TI  - Thumb motor performance varies by movement orientation, direction, and device
      size during single-handed mobile phone use.
AB  - OBJECTIVE: The aim of this study was to determine if thumb motor performance
      metrics varied by movement orientation, direction, and device size during single
      handed use of a mobile phone device. BACKGROUND: With the increased use of mobile
      phones, understanding how design factors affect and improve performance can
      provide better design guidelines. METHOD: A repeated measures laboratory
      experiment of 20 right-handed participants measured the thumb tip's 3-D position
      relative to a phone during reciprocal tapping tasks across four phone designs and
      four thumb tip movement orientations. Each movement orientation included two
      movement directions: an "outward" direction consisting in CMC (carpometacarpal)
      joint flexion or abduction movements and an "inward" direction consisting in CMC
      joint extension or adduction movements. Calculated metrics of the thumb's motor
      performance were Fitts' effective width and index of performance. RESULTS: Index
      of performance varied significantly across phones, with performance being
      generally better for the smaller devices. Performance was also significantly
      higher for adduction-abduction movement orientations compared to flexion
      extension, and for "outward" compared to "inward" movement directions.
      CONCLUSION: For single-handed device use, adduction-abduction-type movements on
      smaller phones lead to better thumb performance. APPLICATION: The results from
      this study can be used to design new mobile phone devices and keypad interfaces
      that optimize specific thumb motions to improve the user-interface experience
      during single-handed use.

PMID- 22409103
TI  - Detecting confusion using facial electromyography.
AB  - OBJECTIVE: The ability to detect confusion using facial electromyography (EMG)
      was evaluated. BACKGROUND: Facial EMG has been useful in detecting various
      emotional states. Another state potentially detectable from facial musculature is
      confusion. Confusion reflects a loss of understanding or, in a dynamic
      environment, a loss of situation understanding or situation awareness. METHOD:
      For this study, 24 participants listened to a confusing and a neutral audio
      passage while they were monitored with EMG. Electrical activity of the right and
      left corrugator supercilii, the right zygomaticus major, and right depressor
      anguli oris was recorded. Participants also reported whether they felt confused
      during the experimental passage. Finally, they were asked to pose facial
      expressions. Two raters assessed responses in the graphed EMG data for evidence
      of activation near a confusing sentence in the passage. RESULTS: EMG revealed
      confusion in 21 of 24 (87.5%) participants, even in some participants who did not
      admit confusion. Posed expressions of confusion differed somewhat from
      spontaneous expressions elicited during the experimental passage. CONCLUSION: EMG
      was effective in detecting confusion, regardless of operator self-report. Not all
      muscles in the face were important for the detection of confusion: The
      zygomaticus major led to a large number of false positives. APPLICATION: EMG can
      be an effective addition to a sensor suite designed to monitor the cognitive
      state of operators of systems.

PMID- 22409104
TI  - Dealing with task interruptions in complex dynamic environments: are two heads
      better than one?
AB  - OBJECTIVE: This study examined whether teaming up mitigates individual
      vulnerability to task interruptions in complex dynamic situations. BACKGROUND:
      Omnipresent in everyday multitasking environments, task interruptions are usually
      detrimental to individual performance. This is particularly crucial in dynamic
      command and control (C2) safety-critical contexts because of the additional
      challenge imposed by the continually evolving situation during the interruption.
      METHOD: We employed a firefighting microworld to simulate C2 in the context of
      supervisory control to examine the relative impact of interruptions on
      participants working in a functional dyad versus operators working alone.
      RESULTS: Although task interruption was detrimental to participants' efficacy of
      monitoring resources, the negative impact of interruption was reduced for those
      working in teams. Teaming up translated into faster resumption time, but only if
      both teammates were interrupted simultaneously. Interrupting only one team member
      was associated with increased postinterruption communications and slower
      resumption time. CONCLUSION: These findings suggest that in complex dynamic
      situations working in a small team confers more resistance to task interruption
      than working alone by virtue of the reduced individual workload typical of
      teamwork. The benefit of collaborative work seems nevertheless mediated by the
      coordination and communication overhead associated with teamwork. APPLICATION:
      The present findings have practical implications for operators dealing with
      unexpected events such as task interruptions in C2 environments.

PMID- 22409105
TI  - Team knowledge research: emerging trends and critical needs.
AB  - OBJECTIVE: This article provides a systematic review of the team knowledge
      literature and guidance for further research. BACKGROUND: Recent research has
      called attention to the need for the improved study and understanding of team
      knowledge. Team knowledge refers to the higher level knowledge structures that
      emerge from the interactions of individual team members. METHOD: We conducted a
      systematic review of the team knowledge literature, focusing on empirical work
      that involves the measurement of team knowledge constructs. For each study, we
      extracted author degree area, study design type, study setting, participant type,
      task type, construct type, elicitation method, aggregation method, measurement
      timeline, and criterion domain. RESULTS: Our analyses demonstrate that many of
      the methodological characteristics of team knowledge research can be linked back
      to the academic training of the primary author and that there are considerable
      gaps in our knowledge with regard to the relationships between team knowledge
      constructs, the mediating mechanisms between team knowledge and performance, and
      relationships with criteria outside of team performance, among others. We also
      identify categories of team knowledge not yet examined based on an organizing
      framework derived from a synthesis of the literature. CONCLUSION: There are clear
      opportunities for expansion in the study of team knowledge; the science of team
      knowledge would benefit from a more holistic theoretical approach. APPLICATION:
      Human factors researchers are increasingly involved in the study of teams. This
      review and the resulting organizing framework provide researchers with a summary
      of team knowledge research over the past 10 years and directions for improving
      further research.

PMID- 22409106
TI  - Human-human reliance in the context of automation.
AB  - OBJECTIVE: The current study examined human-human reliance during a computer
      based scenario where participants interacted with a human aid and an automated
      tool simultaneously. BACKGROUND: Reliance on others is complex, and few studies
      have examined human-human reliance in the context of automation. Past research
      found that humans are biased in their perceived utility of automated tools such
      that they view them as more accurate than humans. Prior reviews have postulated
      differences in human-human versus human-machine reliance, yet few studies have
      examined such reliance when individuals are presented with divergent information
      from different sources. METHOD: Participants (N = 40) engaged in the Convoy
      Leader experiment.They selected a convoy route based on explicit guidance from a
      human aid and information from an automated map. Subjective and behavioral human
      human reliance indices were assessed. Perceptions of risk were manipulated by
      creating three scenarios (low, moderate, and high) that varied in the amount of
      vulnerability (i.e., potential for attack) associated with the convoy routes.
      RESULTS: Results indicated that participants reduced their behavioral reliance on
      the human aid when faced with higher risk decisions (suggesting increased
      reliance on the automation); however, there were no reported differences in
      intentions to rely on the human aid relative to the automation. CONCLUSION: The
      current study demonstrated that when individuals are provided information from
      both a human aid and automation,their reliance on the human aid decreased during
      high-risk decisions. APPLICATION: This study adds to a growing understanding of
      the biases and preferences that exist during complex human-human and human
      machine interactions.

PMID- 22409107
TI  - Enhanced perception and performance by multimodal threat cueing in simulated
      combat vehicle.
AB  - OBJECTIVE: In a simulated combat vehicle, uni-, bi-, and trimodal cueing of
      direction to threat were compared with the purpose to investigate whether
      multisensory redundant information may enhance dynamic perception and
      performance. BACKGROUND: Previous research has shown that multimodal display
      presentation can enhance perception of information and task performance. METHOD:
      Two experiments in a simulated combat vehicle were performed under the
      instructions to turn the vehicle toward the threat as fast and accurately as
      possible after threat cue onset. In Experiment 1, direction to threat was
      presented by four display types: visual head-down display, tactile belt, 3-D
      audio, and trimodal with the three displays combined. In Experiment 2, direction
      to threat was presented by three display types: visual head-up display (HUD)-3-D
      audio, tactile belt-3-D audio, and trimodal with HUD, tactile belt, and 3-D audio
      combined. RESULTS: In Experiment I,the trimodal display provided overall best
      performance and perception of threat direction. In Experiment 2, both the
      trimodal and HUD--3-D audio displays led to overall best performance, and the
      trimodal display provided overall the best perception of threat direction. None
      of the trimodal displays induced higher mental workload or secondary task
      interference. CONCLUSION: The trimodal displays provided overall enhanced
      perception and performance in the dynamically framed threat scenario and did not
      entail higher mental workload or decreased spare capacity. APPLICATION: Trimodal
      displays with redundant information may contribute to safer and more reliable
      peak performance in time-critical dynamic tasks and especially in more extreme
      and stressful situations with high perceptual or mental workload.

PMID- 22409108
TI  - Constrained path tracking at varying angles in a mouse tracking task.
AB  - OBJECTIVE: This study was aimed to determine the effects of direction and path
      length on movement time when traversing a constrained path of width, W, in a
      mouse tracking task. BACKGROUND: Tracking within constrained paths has been
      demonstrated to hold in many applications. Movement time and velocity of movement
      have shown very similar relationships, possibly because of the lack of extreme
      testing conditions. Most previous research evaluated conditions with only
      constant path length (A) of movement. METHOD: A total of 15 participants
      performed a mouse steering task within a constrained path at various angles. The
      independent variables were track width (W), path length, and path angle. Movement
      time was the dependent variable. RESULTS: Analyses showed a significant effect of
      movement direction on movement time, and the relationship was approximately
      sinusoidal and symmetrical about the horizontal axis. Path length had a
      significant effect on speed of movement, which was not that apparent on movement
      time. At low A/W values, movements appeared to be ballistic. CONCLUSION: Tracking
      within constrained paths can be modeled to account for the effect of path angle.
      APPLICATION: Vertical hand movements, especially within constrained paths, may
      not be ideal from a performance and biomechanical standpoint. The performance
      curve gradients are a good way to evaluate and standardize the testing of input
      devices and to define acceptable speeds for various tolerances in computer and
      industrial tasks that involve angular motions. The results of this experiment
      will help designers to optimize products and training programs.

PMID- 22409109
TI  - Reflections.

PMID- 22409110
TI  - Encore! Encore!

PMID- 22409111
TI  - Raising health care provider awareness of sexually transmitted disease in
      patients over age 50.
AB  - An increase in sexual activity among persons over age 50 has resulted in a
      dramatically increased prevalence of sexually transmitted diseases (STDs),
      including higher rates of HIV/AIDS, syphilis, gonorrhea, and chlamydia. Raising
      awareness of health care providers regarding STDs in this age group is essential
      for appropriate prevention and treatment.

PMID- 22409112
TI  - A qualitative study of phlebotomy device selection.
AB  - Limited research exists comparing Vacutainer versus butterfly phlebotomy devices.
      The purpose of this study was to examine decision processes staff use when
      choosing a device. A qualitative, purposive sampling was used and determined a
      gap between correct device use and reported practice. Applied findings can
      enhance employee safety.

PMID- 22409113
TI  - Assessment of nurses' and therapists' occupational musculoskeletal injuries.
AB  - INTRODUCTION: Occupational musculoskeletal injuries are serious issues facing
      health care professionals and health care facilities in the United States today.
      PURPOSE: The purpose of the study was to investigate health care worker
      occupational injury patterns to gain better understanding of the injuries.
      METHOD: A descriptive study was conducted at a 497-bed hospital to investigate
      the patterns of occupational injuries of nursing and therapy personnel. A
      secondary data analysis was conducted on data collected by the occupational
      health department of a hospital. FINDINGS: Two years of occupational injury
      reports were analyzed. The evidence showed the overall injury rate between nurses
      and therapists was similar. Health care professionals ages 50 to 59 were
      employees injured most frequently. The most injuries occurred between 9:30 a.m.
      and 11:30 a.m., and Wednesday was the most frequent day of injury. Most employees
      reported the injury on the day of the injury and did not lose work time from the
      event. Surgical services department had the most injuries, and back injuries were
      the most common type of musculoskeletal injury. CONCLUSION: By recognizing the
      type of injuries, location of injuries, time of injuries, and impact of injuries,
      nurses can make changes to decrease work-related musculoskeletal injuries and
      improve work environments.

PMID- 22409114
TI  - Are patients with breast cancer satisfied with their decision making? A pilot
      study.
AB  - This pilot study measured participants' comfort with their decision making to
      have a lumpectomy and radiation or total mastectomy to treat their breast cancer.
      Findings showed 87% of the patients believed they had made an informed choice and
      were satisfied with their decision making regarding their surgical procedure
      selection.

PMID- 22409115
TI  - Patient education on heart attack response: is rehearsal the critical factor in
      knowledge retention?
AB  - Recognition and prompt response to signs and symptoms of an acute myocardial
      infarction are among the most important areas of patient education for nurses in
      any setting. This study supports the use of one-to-one teaching with rehearsal
      for knowledge acquisition needed by patients and families to improve the ability
      to recognize and respond to symptoms of a heart attack.

PMID- 22409116
TI  - Factors influencing the implementation of a point-of-care screening tool for
      delirium.
AB  - Given the ample evidence delirium in hospitalized older adults is underdiagnosed
      and not recognized by nurses up to 85% of the time, interventions are needed at
      the point of care to assist nurses in recognizing delirium. In this qualitative
      study, factors that might influence the implementation of a point-of-care
      screening tool for delirium were examined.

PMID- 22409117
TI  - Clinical support for the off-shift nurse and the graduate nurse: the clinical
      rock stars.
AB  - Turnover of medical-surgical nurses can be distressing and costly Establishment
      of the clinical resource specialist role can provide a valuable resource to off
      shift RNs and have a positive impact on job satisfaction.

PMID- 22409118
TI  - The impact of nurse rounding on patient satisfaction in a medical-surgical
      hospital unit.
AB  - This study, led by the chief nursing officer and the patient advocate of a
      community hospital, set out to determine the impact of nurse rounding on
      inpatients in a medical-surgical unit. The introduction of the 4 P Program, a
      nurse rounding program designed to anticipate and meet basic patient needs at
      least every 2 hours, had an almost immediate impact as measured by overall
      patient satisfaction.

PMID- 22409119
TI  - Nurse migration: what is its impact?

PMID- 22409120
TI  - Whipple pancreatoduodenectomy surgery for the treatment of pancreatic cancer.

PMID- 22409121
TI  - Comprehensive case study--diabetic ketoacidosis.

PMID- 22409122
TI  - The 2-minute warning part IV: close out the game and then celebrate!

PMID- 22409123
TI  - T-tests.

PMID- 22409124
TI  - Reducing risk factors.

PMID- 22409125
TI  - Where are the spirits of yesteryear?

PMID- 22409126
TI  - Emergency medical services in stroke care: a Rhode Island perspective.

PMID- 22409127
TI  - Intra-arterial therapy for acute stroke: trials and tribulations.
AB  - Intra-arterial therapy (IAT) for acute ischemic stroke has undergone great
      evolution during the past decade. While intra-venous therapy remains the standard
      of care for eligible patients, there are those patients in whom IV tPA is
      contraindicated, or those who fail to improve following IV tPA. In those cases,
      patients with accessible arterial occlusions may benefit from IAT, especially
      when recanalization can occur within six hours from symptom onset. Future
      advancements in device development and patient selection may further improve
      outcomes.

PMID- 22409128
TI  - Novel stroke rehabilitation interventions.

PMID- 22409129
TI  - Primary stroke prevention and community education.

PMID- 22409130
TI  - Secondary stroke prevention in 2011: an update on available options.

PMID- 22409131
TI  - The importance of stroke units.

PMID- 22409132
TI  - The 'golden hour' treatment of acute ischemic stroke.

PMID- 22409133
TI  - Sexual orientation and health risk behaviors among Rhode Island public high
      school students, 2009.

PMID- 22409134
TI  - The harsh vocabulary of intemperance.

PMID- 22409135
TI  - A little touch of heresy.

PMID- 22409136
TI  - Free riders.

PMID- 22409137
TI  - Saliva tests now can accurately predict age.

PMID- 22409138
TI  - Lipid characterization of human saliva.
AB  - Salivary lipids have been scarcely studied, and the reported results present
      disparities. This literature review is presented based on the importance of
      saliva as a diagnostic and/or prognostic medium for various diseases, its lipid
      content, and on its potential use for the analysis of nutritional markers that
      contribute to the study of diseases related to lipid consumption and metabolism.

PMID- 22409139
TI  - A simple technique for increasing the occlusal vertical dimension of removable
      denture wearers.
AB  - This article describes a simple and efficient technique for increasing the
      occlusal vertical dimension of removable denture wearers. Functionally generated
      path technique is carried out by using gothic arch tracing, and the existing
      mandibular overdenture is modified for interim use.

PMID- 22409140
TI  - Clinical management of a unique case of fusion between supernumerary canine and
      maxillary first premolar.
AB  - Fusion is one of the few developmental disorders that may account for alteration
      in morphology and number of teeth in the dental arch. This case report presents a
      unique case of fusion between supernumerary canine and maxillary first premolar,
      the associated problems, and their comprehensive clinical management.

PMID- 22409141
TI  - Correlation between cervical vertebral and dental maturity in Iranian subjects.
AB  - Determination of the skeletal maturation is extremely important in clinical
      orthodontics. Cervical vertebral maturation is an effective diagnostic tool for
      determining the adolescent growth spurt. The aim of this study was to investigate
      the correlation between the stages of calcification of teeth and the cervical
      vertebral maturity stages.

PMID- 22409142
TI  - Anti-viral inhibitor binding to influenza neuraminidase by MALDI mass
      spectrometry.
AB  - A matrix-assisted laser desorption ionization (MALDI) mass spectrometry-based
      approach is applied to identify active site domains within influenza
      neuraminidase that bind the antiviral inhibitors zanamivir (ZANA) and 2-deoxy-2,3
      didehydro-N-acetylneuraminic acid (DANA). Combined data from the tryptic and Glu
      C endoproteinase digests of neuraminidase-inhibitor complexes have identified
      binding peptides that contain the active site residues Arg118, Glu119, Arg156,
      Glu276, and Tyr406. The binding of these residues was confirmed from the analysis
      of available X-ray crystal structures. The ability to identify peptides within
      the active sites of proteins and likely binding residues provides both a rapid
      and relatively high throughput approach with which to screen protein-drug
      interactions by MALDI mass spectrometry.

PMID- 22409143
TI  - Effects of a coactor's focus of attention on task performance.
AB  - Coactors take into account certain aspects of each other's tasks even when this
      is not required to perform their own task. The present experiments investigated
      whether the way a coactor allocates attention affects one's own attentional
      relation to stimuli that are attended jointly (Experiment 1), individually
      (Experiment 2), or in parallel (Experiments 3 and 4). Pairs of participants
      sitting next to each other performed a two-choice Navon task, responding to the
      identity of letters. Participants' tasks either required the same focus of
      attention (e.g., both attending to local stimulus features) or different foci of
      attention (e.g., one attending to local and the other to global features).
      Results revealed a significant slow-down of responses when participants focused
      on different features, suggesting that the coactor's attentional focus induced a
      conflict that affected the selection of one's own focus. This effect disappeared
      when no other person was present, and when mutual visual access to each other's
      stimuli was disrupted, but did not depend on a triangular relationship between
      participants and stimuli. Our findings extend previous research on joint
      attention and task corepresentation in revealing that representations of a
      coactor's task can include a specification of her focus of attention.

PMID- 22409144
TI  - Effect of viewing plane on perceived distances in real and virtual environments.
AB  - Three experiments examined perceived absolute distance in a head-mounted display
      virtual environment (HMD-VE) and a matched real-world environment, as a function
      of the type and orientation of the distance viewed. In Experiment 1, participants
      turned and walked, without vision, a distance to match the viewed interval for
      both egocentric (viewer-to-target) and exocentric (target-to-target) extents.
      Egocentric distances were underestimated in the HMD-VE while exocentric distances
      were estimated similarly across environments. Since egocentric distances were
      displayed in the depth plane and exocentric distances in the frontal plane, the
      pattern of results could have been related to the orientation of the distance or
      to the type of distance. Experiments 2 and 3 tested these alternatives.
      Participants estimated exocentric distances presented along the depth or frontal
      plane either by turning and walking (Experiment 2) or by turning and throwing a
      beanbag to indicate the perceived extent (Experiment 3). For both Experiments 2
      and 3, depth intervals were underestimated in the HMD-VE compared to the real
      world. However, frontal intervals were estimated similarly across environments.
      The findings suggest anisotropy in HMD-VE distance perception such that distance
      underestimation in the HMD-VE generalizes to intervals in the depth plane, but
      not to intervals in the frontal plane.

PMID- 22409145
TI  - Selective attention to perceptual dimensions and switching between dimensions.
AB  - In the present experiments, the question being addressed was whether switching
      attention between perceptual dimensions and selective attention to dimensions are
      processes that compete over a common resource? Attention to perceptual dimensions
      is usually studied by requiring participants to ignore a never-relevant
      dimension. Selection failure (Garner's Interference, GI) is indicated by poorer
      performance in the filtering condition (when this dimension varies) as compared
      with baseline (when it is fixed). Switching between perceptual dimensions is
      usually studied with the task switching paradigm. In the present experiments,
      attention switching was manipulated by using single-task blocks and blocks in
      which participants switched between tasks or dimensions in reaction to task cues,
      and attention to dimensions was assessed by including a third, never-relevant
      dimension that was either fixed or varied randomly. In Experiments 1 (long cue
      target interval, CTI) and 2 (short CTI), the tasks involved shape and color and
      the never-relevant dimension (texture) was chosen to be separable from them. In
      Experiments 3 (long CTI) and 4 (short CTI), the tasks involved shape and
      brightness and the never-relevant dimension, saturation, was chosen to be
      separable from shape and integral with brightness. Task switching did not
      generate GI but a short CTI did. Thus, switching and filtering generally do not
      compete over central limited resources unless under tight time pressure.
      Experiment 3 shows GI in the brightness task but not in the shape task,
      suggesting that participants switched their attention between brightness and
      shape when they switched tasks.

PMID- 22409146
TI  - On the photomagnetism of nitronyl nitroxide, imino nitroxide, and verdazyl
      substituted azobenzene.
AB  - The cis- and trans-azobenzenes are known as photochromic isomers with the trans-
      converting into the cis-form and vice versa upon irradiation with specific
      wavelengths. We have quantum chemically investigated the cis- and trans-forms of
      substituted azobenzene diradicals, with two nitronyl nitroxides, imino nitoxides,
      or verdazyls at para positions and serving as monoradical centers, to determine
      whether they can exhibit a photoassisted magnetic crossover. Geometries of both
      substituted and unsubstituted molecules have been optimized by density functional
      (DF) method UB3LYP using the 6-311G(d,p) basis set. Optimization of the geometry
      of the cis isomers has required special care. Single point singlet, triplet, and
      broken symmetry calculations have been done using 6-311++G(3df, 3pd) basis set.
      The magnetic exchange coupling constants have been estimated from the broken
      symmetry calculations. Absorption wavelengths have been estimated for both
      substituted and unsubstituted species from time-dependent DF treatment using
      restricted spin-polarized methodology RB3LYP and 6-311++G(3df, 3pd) basis set.
      From the similarity in the calculated absorption wavelengths for the
      unsubstituted and substituted azobenzenes, and the increased oscillator strengths
      (f) for the substituted species, we predict that the diradical isomers would be
      strongly photochromic. From our triplet state and broken symmetry calculations,
      we predict that both the cis- and the trans-diradicals are antiferromagnetically
      coupled. This prediction is consistent with the spin alternation rule, and the
      possibility of a magnetic crossover is nonexistent for these species.

PMID- 22409147
TI  - Phosphine-free Suzuki-Miyaura cross-coupling in aqueous media enables access to 2
      C-aryl-glycosides.
AB  - A general strategy for the synthesis of 2-aryl-glycals and their elaboration to 2
      C-aryl-alpha-glycosides and 1,5-anhydro-2-C-aryl-2-deoxy alditols are described.
      The use of reliable, efficient phosphine-free Suzuki-Miyaura cross-coupling of 2
      iodoglycals in aqueous media as a key step proceeds with complete
      regioselectivity at C-2 and enables access to 2-aryl-glycals with different
      configurations in excellent yields.

PMID- 22409148
TI  - Cytotoxic diterpenoids from Sapium insigne.
AB  - Chemical investigation into the twigs and leaves of Sapium insigne afforded seven
      new diterpenoids, sapinsignoids A-G (1-7), together with 10 known diterpenoids.
      The structures of 1-7 were assigned on the basis of detailed spectroscopic
      analysis and chemical degradation. Compounds 1-4 exhibited significant
      cytotoxicity against the A-549 tumor cell line (IC(50) 0.2-1.8 MUM), while
      compounds 1-3 showed moderate cytotoxicity against the HL-60 cell line (IC(50)
      2.7-6.5 MUM).

PMID- 22409149
TI  - Pulsed plasmachemical deposition of highly proton conducting composite sulfonic
      acid-carboxylic acid films.
AB  - Graft polymerization of sulfonic acid monomers onto structurally well-defined
      pulsed plasma poly(maleic anhydride) layers yields a composite carboxylic acid
      sulfonic acid network. These bifunctional films are shown to exhibit high proton
      conductivity (125 mS cm(-1)) as well as good stability in water.

PMID- 22409150
TI  - Topical simvastatin improves the pro-angiogenic and pro-osteogenic properties of
      bioglass putty in the rat calvaria critical-size model.
AB  - Abstract   Objective: To describe the effect of bioactive glass putty with and
      without topical simvastatin on new bone formation in critical-sized defects of
      rat calvaria. Study design: A calvarial bone defect was created in 20 male Wistar
      rats and filled with bioactive glass alone (n=10) or combined with simvastatin
      (n=10). After 4 weeks, the defects were histomorphometrically evaluated for
      volume fraction (Vv) of woven bone, vessel density, bioglass quantity, and
      inflammation.  Results:  Compared to the bioglass-only group, rats treated with
      simvastatin had greater Vv of blood vessels (3.3%+0.7 vs 1.6%+0.1, P=0.0002) and
      new bone (2.3%+0.2 vs 1.8%+2.5, P=0.003). The Vv of the bioglass remnants in the
      bioglass-only group was higher than in the group treated with simvastatin (2.4%
      +0.08 vs 1.7%+0.3, P<0.0004). Chronic inflammation was noted in one rat from each
      group.  Conclusion: Topical simvastatin seems to improve the pro-angiogenic and
      pro-osteogenic properties of bioglass putty in rat calvaria critical-size defects
      without significant inflammation.

PMID- 22409151
TI  - Addition of time-dependent covariates to a survival model significantly improved
      predictions for daily risk of hospital death.
AB  - RATIONAL, AIMS AND OBJECTIVES: The study aims to determine the extent to which
      the addition of post-admission information via time-dependent covariates improved
      the ability of a survival model to predict the daily risk of hospital death.
      METHOD: Using administrative and laboratory data from adult inpatient
      hospitalizations at our institution between 1 April 2004 and 31 March 2009, we
      fit both a time-dependent and a time-fixed Cox model for hospital mortality on a
      randomly chosen 66% of hospitalizations. We compared the predictive performance
      of these models on the remaining hospitalizations. RESULTS: All comparative
      measures clearly indicated that the addition of time-dependent covariates
      improved model discrimination and prominently improved model calibration. The
      time-dependent model had a significantly higher concordance probability (0.879
      versus 0.811) and predicted significantly closer to the number of observed deaths
      within all risk deciles. Over the first 32 admission days, the integrated
      discrimination improvement (IDI) and net reclassification improvement (NRI) were
      consistently above zero (average IDI of +0.0200 and average NRI of 62.7% over the
      first 32 days). CONCLUSIONS: The addition of time-dependent covariates
      significantly improved the ability of a survival model to predict a patient's
      daily risk of hospital death. Researchers should consider adding time-dependent
      covariates when seeking to improve the performance of survival models.

PMID- 22409152
TI  - Cleaning potential of glycine air-flow application in an in vitro peri
      implantitis model.
AB  - OBJECTIVES: The study aimed to assess the accessibility of a glycine powder
      blasting device to implant surfaces in models imitating different peri
      implantitis defects. The null hypothesis was that the device allows for complete
      surface decontamination in all defect types. MATERIALS AND METHODS: Eighteen
      implants were dip-coated and placed in resin blocks with different defect
      morphologies. Vertical bone angulations of 90 degrees , 60 degrees , 30 degrees 
      and 15 degrees  were chosen and the implants were treated for 10 s using an air
      flow device employing glycine powder. Once removed, photographs from the implants
      were taken in three directions: perpendicularly (90 degrees ) to the implant axis
      and with an angulation of 60 degrees  and 120 degrees , the latter ones to assess
      the coronal and apical thread areas. The area with residual color represented
      areas, which were not accessible to the powder. This area was planimetrically
      assessed. Medians and inter-quartile ranges (IQR) of the percentage of uncleaned
      surfaces were calculated and nonparametric paired and unpaired statistical
      analyses were performed. RESULTS: The median percentages (IQR in brackets) of
      uncleaned areas in the 90 degrees , 60 degrees , 30 degrees  and 15 degrees 
      defects were of 3%(A) (6), 8%(A) (4), 24%(B) (8), and 51%(C) (13), respectively
      (different superscript capital letters represent statistically significant
      differences; P < 0.0001). The upper aspects of the threads (coronal faces) were
      significantly better cleaned than the lower ones (P < 0.001). This finding was
      more pronounced in narrower defects. CONCLUSION: Although a complete surface
      decontamination could not be performed in any of the defects, the biggest part of
      the surface could be cleaned in the larger defects. Especially in narrow defects
      and under the threads, residually stained areas remain on the implant surfaces.

PMID- 22409153
TI  - Comparison of the effectiveness of nonablative fractional laser versus ablative
      fractional laser in thyroidectomy scar prevention: A pilot study.
AB  - A scar is a mark that remains after the healing of a wound or other morbid
      processes. In the past, treatment was mainly focused on severe scarring, such as
      the hypertrophic and burn scars. However, scars from relatively minor wounds can
      also be stressful. The site of an open thyroidectomy is the anterior neck, a
      prominently exposed part of the body, where postoperative scarring can cause
      patients distress. The cosmetic outcome of the scar after thyroidectomy is of
      particular importance to women, who constitute the majority of patients with
      thyroid disease. Active prevention is more likely to yield better cosmetic
      results and would require fewer treatment sessions and less expense than scar
      revision procedures. Many interventions have been proposed, but there is yet no
      universal consensus on optimal treatment. Recently, focus has been made on 'laser
      scar prevention', where various types of lasers have been used to improve the
      appearance of scars. The purpose of this study was to improve the appearance of
      scars, by laser intervention of the wound healing process. In this pilot study,
      we comparatively examined the effect of non-ablative 1550-nm fractional Er: glass
      laser and ablative 2940-nm fractional Er: YAG laser on fresh surgical scars of
      patients with Fitzpatrick skin type III-IV.

PMID- 22409154
TI  - The larger exercise stroke volume in endurance-trained men does not result from
      increased left ventricular early or late inflow or tissue velocities.
AB  - AIM: To determine whether the larger exercise stroke volume in senior endurance
      trained athletes results from an attenuation of age-related alterations in left
      ventricular (LV) early diastolic filling or a more vigorous late filling.
      METHODS: Body composition (DEXA), VO(2)peak, stroke volume (CO(2) rebreathing)
      and Doppler measures of early and late mitral inflow and mitral annular
      velocities were collected at seated upright rest and heart rate-matched exercise
      (100 and 120 bpm) in trained and untrained younger (18-30 years) men and trained
      and untrained older (60-80 years) healthy men. RESULTS: Ageing had a greater
      effect than training status on seated rest mitral inflow and tissue Doppler
      imaging parameters, as shown by a lower peak early-to-late mitral inflow velocity
      ratio (E/A ratio) and slower peak early mitral annular velocity (Em) in older
      compared with younger men. Exercise stroke volume was unaffected by healthy
      ageing; however, Em, an index of early LV lengthening rate and relaxation, was
      slower (P < 0.001), while measures of atrial systole were increased (P < 0.001)
      during exercise in older men. Stroke volume during exercise was larger in the
      trained men (P < 0.001); however, early and late mitral inflow and tissue
      velocities were not different between trained and untrained men. CONCLUSION: The
      larger exercise stroke volume in trained older male athletes does not seem to be
      related to faster filling or lengthening velocities during early or late filling.
      Thus, a larger, more compliant left ventricle in combination with an increased
      blood volume may explain the larger LV filling volumes in trained seniors.

PMID- 22409155
TI  - Structure dependence of charged states in "linear" polyaniline as studied by in
      situ ATR-FTIR spectroelectrochemistry.
AB  - The electrochemical doping of emeraldine salt and emeraldine bases with different
      weight average molecular weights was studied by in situ Fourier transform
      infrared (FTIR) spectroelectrochemistry using attenuated total reflection (ATR)
      technique. The formation and stabilization of charge carriers in polyaniline
      during p-doping was followed in dependence of the chain branching. The potential
      dependence of the IR bands during the oxidation of the polymer clearly
      demonstrates the formation of the different charged polymer structures (pi
      dimers, polarons, and bipolarons). It is shown that IR bands usually attributed
      to a semiquinoid polaron lattice correspond in fact to doubly charged species, pi
      dimers, which are face-to-face complexes of two polarons. Bands corresponding
      exclusively to polarons have been identified at 1266, 1033, and 1010 cm(-1),
      suggesting that polarons are predominantly stabilized on the linear segments near
      the polymer branches by phenazine.

PMID- 22409156
TI  - Assessment of antibiofilm activity of magnesium fluoride nanoparticles-stabilized
      oil-in-water nanosized emulsion.
AB  - CONTEXT: Magnesium fluoride (MgF(2)) nanoparticles-stabilized oil-in-water
      nanosized emulsion was prepared and assessed for its antiadherent and antibiofilm
      activities over glass coupons against pathogenic microorganisms like Escherichia
      coli and Staphylococcus aureus. OBJECTIVE: The major objectives of this paper are
      to synthesis MgF(2) nanoparticles, to prepare MgF(2) nanoparticles-stabilized
      nanosized emulsion, to coat glass coupons with MgF(2) nanoparticles and
      nanoparticles-stabilized emulsion, to challenge the emulsion or nanoparticles
      coated and uncoated glass surfaces with fresh bacterial cultures over 18 h for
      biofilm formation, and to evaluate the extended antibiofilm activity of the
      coupons coated with either nanoparticles or emulsion in restricting the bacterial
      growth and biofilm formation. RESULTS AND DISCUSSION: Uncoated surfaces supported
      a massive biofilm formation (12.6 * 10(11) and 11.6 * 10(11) CFU cm(-2) for E.
      coli and S. aureus respectively for the 3rd day) while emulsion-coated surfaces
      dramatically restricted bacterial colonization (9.3 and 8.0 CFU cm(-2) for E.
      coli and S. aureus respectively). These results suggested that MgF(2)
      nanoparticles-stabilized emulsion is effective in restraining bacterial
      colonization on glass surfaces. CONCLUSION: Although the glass coupons are
      selected as a model biomaterial surface, similar or increased antibiofilm action
      would be expected when this 'hybrid' nanoparticulate system is coated on other
      types of biomaterial surfaces such as intraocular lenses, catheters, etc.

PMID- 22409157
TI  - Burkholderia phytofirmans PsJN acclimates grapevine to cold by modulating
      carbohydrate metabolism.
AB  - Low temperatures damage many temperate crops, including grapevine, which, when
      exposed to chilling, can be affected by symptoms ranging from reduced yield up to
      complete infertility. We have previously demonstrated that Burkholderia
      phytofirmans PsJN, a plant growth-promoting rhizobacteria (PGPR) that colonizes
      grapevine, is able to reduce chilling-induced damage. We hypothesized that the
      induced tolerance may be explained at least partly by the impact of bacteria on
      grapevine photosynthesis or carbohydrate metabolism during cold acclimation. To
      investigate this hypothesis, we monitored herein the fluctuations of
      photosynthesis parameters (net photosynthesis [P(n)], intercellular CO(2)
      concentration, stomatal conductances, PhiPSII, and total chlorophyll
      concentration), starch, soluble sugars (glucose, fructose, saccharose, mannose,
      raffinose, and maltose), and their precursors during 5 days of chilling exposure
      (4 degrees C) on grapevine plantlets. Bacterization affects photosynthesis in a
      non-stomatal dependent pattern and reduced long-term impact of chilling on P(n).
      Furthermore, all studied carbohydrates known to be involved in cold stress
      tolerance accumulate in non-chilled bacterized plantlets, although some of them
      remained more concentrated in the latter after chilling exposure. Overall, our
      results suggest that modification of carbohydrate metabolism in bacterized
      grapevine plantlets may be one of the major effects by which this PGPR reduces
      chilling-induced damage.

PMID- 22409158
TI  - Effect of Aspergillus oryzae-challenged germination on soybean isoflavone content
      and antioxidant activity.
AB  - Application of microbial stress to soybean during germination induces the
      accumulation of phytoalexins, which have many health benefits. In this study, the
      effects of stress induced by Aspergillus oryzae on the phytochemical composition
      of germinating soybeans were investigated, and their radical scavenging activity
      was compared with those of ungerminated (US) and germinated (GS) soybeans.
      Additionally, the antioxidant activity of coumestrol, a soybean phytoalexin,
      against hydrogen peroxide-induced reactive oxygen species (ROS) was investigated
      in HepG2 cells. A. oryzae exposure significantly decreased the total isoflavone
      content and induced coumestrol and glyceollin I. A. oryzae-challenged germinated
      soybeans exhibited the highest radical scavenging activity (IC(50) = 0.55 mg/mL)
      as compared to US and GS. Coumestrol exhibited significantly higher radical
      scavenging activity than daidzein and genistein. Furthermore, coumestrol
      significantly prevented hydrogen peroxide-induced ROS production and lipid
      peroxidation and inhibited decreases in cell viability, intracellular glutathione
      (GSH) levels, and superoxide dismutase (SOD) activity. These results indicate
      that using food-grade A. oryzae to elicit the biosynthesis of phytoalexins alters
      the secondary metabolite profiles of the soybeans and offers enhanced bioactivity
      of soybean as a functional food ingredient.

PMID- 22409160
TI  - Correlates of intimate partner psychological aggression perpetration in a
      clinical sample of alcoholic men.
AB  - This study longitudinally examined correlates of intimate partner psychological
      aggression in a sample of 178 men seeking treatment for alcoholism and their
      partners, building on a previous investigation examining correlates of intimate
      partner physical aggression (Taft et al., 2010). The men were largely Caucasian;
      average age was 41.0 years. Participants completed a battery of questionnaires
      that assessed distal and proximal predictors of psychological aggression
      perpetration. Distal factors, assessed at baseline, included initial alcohol
      problem severity, beliefs about alcohol, and antisocial personality
      characteristics. Proximal factors, assessed at baseline and at follow-ups 6 and
      12 months later, included alcohol and drug use, relationship adjustment, and
      anger. Psychological aggression was assessed at all three time points. Findings
      showed that both groups of variables were associated with psychological
      aggression perpetration. Beliefs that drinking causes relationship problems and
      variables related to alcohol consumption exhibited the strongest associations
      with psychological aggression. The findings are consistent with theoretical
      models that emphasize both distal and proximal effects of drinking on intimate
      partner aggression. Implications for clinical interventions and directions for
      future research are discussed.

PMID- 22409161
TI  - Patient and partner correlates of couple relationship functioning in bipolar
      disorder.
AB  - Extensive research in unipolar depressed and population-based samples has shown
      cross-partner associations between depressive symptoms and relationship
      adjustment. Yet despite evidence that bipolar disorder (BPD) is a more chronic
      and severe illness than unipolar depression, that individuals with BPD are at
      risk for interpersonal dysfunction, and that critical, unsupportive relationships
      are predictive of the course of depressive symptoms in BPD, there have been
      limited efforts to understand the correlates of relationship functioning within
      BPD. The current study addresses this gap in the literature by examining the
      associations between the depressive and manic symptoms of individuals with BPD,
      their partner's depressive symptoms, and relationship functioning, using a
      multimethod, multi-informant approach. Results revealed that the depressive
      symptoms of the individual with BPD were associated with poorer relationship
      functioning, particularly when the partner without BPD also had elevated
      depressive symptoms. In addition, an interaction between the individual with
      BPD's depressive and manic symptoms was observed, such that manic symptoms were
      associated with increased observed hostility and poorer partner relationship
      adjustment, but only when depressive symptoms were also elevated. These effects
      persisted even after overall mental health of both partners was controlled.

PMID- 22409159
TI  - The emotion paradox in the aging brain.
AB  - This paper reviews age differences in emotion processing and how they may relate
      to age-related changes in the brain. Compared with younger adults, older adults
      react less to negative situations, ignore irrelevant negative stimuli better, and
      remember relatively more positive than negative information. Older adults'
      ability to insulate their thoughts and emotional reactions from negative
      situations is likely due to a number of factors, such as being less influenced by
      interoceptive cues, selecting different emotion regulation strategies, having
      less age-related decline in prefrontal regions associated with emotional control
      than in other prefrontal regions, and engaging in emotion regulation strategies
      as a default mode in their everyday lives. Healthy older adults' avoidance of
      processing negative stimuli may contribute to their well-maintained emotional
      well-being. However, when cardiovascular disease leads to additional prefrontal
      white matter damage, older adults have fewer cognitive control mechanisms
      available to regulate their emotions, making them more vulnerable to depression.
      In general, although age-related changes in the brain help shape emotional
      experience, shifts in preferred strategies and goal priorities are also important
      influences.

PMID- 22409163
TI  - Assessment of the human faecal microbiota: I. Measurement and reproducibility of
      selected enzymatic activities.
AB  - BACKGROUND: The intestinal microbial community has major effects on human health,
      but optimal research methods are unsettled. To facilitate epidemiologic and
      clinical research, we sought to optimize conditions and to assess reproducibility
      of selected core functions of the distal gut microbiota, beta-glucuronidase and
      beta-glucosidase bioactivities. METHODS AND RESULTS: A colorimetric kinetic
      method was optimized and used to quantify activities of beta-glucuronidase and
      beta-glucosidase in human faeces. Enzyme detection was optimal with neutral pH,
      snap freezing in liquid nitrogen and rapid thawing to 37  degrees C before
      protein extraction. Enzymatic stability was assessed by delayed freezing for 2-48
      h to mimic field settings. Activities decayed approximately 20% within 2 h and
      40% within 4 h at room temperature. To formally assess reproducibility, 51
      volunteers (25 men; mean age 39) used two devices to self-collect and rapidly
      chill four replicates of a stool. Devices were compared for mean enzymatic
      activities and intraclass correlation coefficients (ICC) in paired replicates of
      the self-collected specimens. Reproducibility was excellent with both devices for
      beta-glucuronidase (ICC 0.92). The larger collection device had significantly
      higher reproducibility for beta-glucosidase (ICC 0.92 vs. 0.76, P < 0.0001) and
      higher mean activities for both enzymes (P < 0.0001). CONCLUSIONS: Optimal
      measurement of these core activities of the microbiota required a sufficient
      quantity of rapidly chilled or frozen specimens collected in phosphate buffered
      saline at pH7.0. Application of these methods to clinical and epidemiologic
      research could provide insights on how the intestinal microbiota affects human
      health.

PMID- 22409165
TI  - Anemia in chronic obstructive pulmonary disease: a readmission prognosis factor.
AB  - OBJECTIVE: The prevalence of comorbid anemia in patients with COPD ranges from
      7.5% to 34%. The aim of this study is to determine if anemia is a risk factor for
      readmission in COPD patients. METHODS: This study analyzed the hospital data of
      289,077 adults with acute exacerbations of COPD admitted to the hospital at any
      public center in Spain, in 2006 and 2007. We calculated the prevalence of anemia
      and compared readmissions between COPD patients with and without anemia. Multiple
      regression analyses were carried out with the aim of determining the risk of
      readmission attributable to anemia, after the correction of possible confounding
      variables. RESULTS: Of the patients with COPD, 9.8% (n = 26,899) had a diagnosis
      of anemia. Anemic patients were older, more likely to be female and had a greater
      comorbidity burden than non-anemic individuals. Multiple regression modeling
      revealed that multiple independent factors were associated with an increased risk
      of readmission in persons with COPD. Anemia was one of the greatest risks: anemic
      patients had a 25% higher risk of readmission than non-anemic patients (odds
      ratio [OR], 1.25; 95% confidence interval [CI] 1.21-1.29). CONCLUSION: Utilizing
      an administrative database the authors found that anemia correlates independently
      with readmission in COPD patients. LIMITATIONS: This is a retrospective cohort
      study and thus subject to multiple forms of bias. Although spirometric evidence
      of COPD was not available, our case identification methods have been previously
      validated and found to be accurate in recognizing COPD.

PMID- 22409166
TI  - It's a small world after all: contrasting hierarchical and edge networks in a
      simulated intelligence analysis task.
AB  - This article presents the rationale behind an important enhancement to a socio
      technical model of organisations and teams derived from military research. It
      combines this with empirical results which take advantage of these enhancements.
      In Part 1, a new theoretical legacy for the model is developed based on
      Ergonomics theories and insights. This allows team communications data to be
      plotted into the model and for it to demonstrate discriminate validity between
      alternative team structures. Part 2 presents multinational data from the
      Experimental Laboratory for Investigating Collaboration, Information-sharing, and
      Trust (ELICIT) community. It was surprising to see that teams in both traditional
      hierarchical command and control and networked 'peer-to-peer' organisations
      operate in broadly the same area of the model, a region occupied by networks of
      communication exhibiting 'small world' properties. Small world networks may be of
      considerable importance for the Ergonomics analysis of team organisation and
      performance. PRACTITIONER SUMMARY: This article is themed around macro and
      systems Ergonomics, and examines the effects of command and control structures.
      Despite some differences in behaviour and measures of agility, when given the
      freedom to do so, participants organised themselves into a small world network.
      This network type has important and interesting implications for the Ergonomics
      design of teams and organisations.

PMID- 22409167
TI  - Following ergonomics guidelines decreases physical and cardiovascular workload
      during cleaning tasks.
AB  - The aim was to investigate the effect of ergonomics guidelines on muscular
      activity, postural and cardiovascular load during cleaning. Eighteen cleaners
      performed 10 min of cleaning tasks in two locations; three min in a laboratory
      and seven min in a lecture room. All participants performed the task with or
      without focusing on ergonomics guidelines (ergonomics/non-ergonomics session).
      Bipolar surface electromyography was recorded bilaterally from upper trapezius
      and erector spinae muscles. A tri-axial accelerometer package was mounted on the
      low back (L5-S1) to measure postural changes, and the cardiovascular load was
      estimated by electrocardiogram. Ergonomics sessions resulted in lower muscular
      load, a more complex pattern of muscular activity, lower range of motion and
      angular velocity of the trunk as well as lower cardiovascular load compared with
      non-ergonomics sessions (p < 0.05). The study highlighted the multiple
      musculoskeletal and cardiovascular benefits of following ergonomics guidelines
      during cleaning tasks. PRACTITIONER SUMMARY: This study investigated the effects
      of following instructive ergonomics guidelines during cleaning tasks (daily
      curriculum of cleaning including mopping, sweeping, changing trash bins and
      cleaning of desks and blackboards). Following the ergonomics guidelines reduces
      the general workload and induces a more complex pattern of muscular activity. The
      study contributes with novel knowledge concerning ergonomics guidelines and work
      techniques.

PMID- 22409164
TI  - Messenger functions of the bacterial cell wall-derived muropeptides.
AB  - Bacterial muropeptides are soluble peptidoglycan structures central to recycling
      of the bacterial cell wall and messengers in diverse cell signaling events.
      Bacteria sense muropeptides as signals that antibiotics targeting cell-wall
      biosynthesis are present, and eukaryotes detect muropeptides during the innate
      immune response to bacterial infection. This review summarizes the roles of
      bacterial muropeptides as messengers, with a special emphasis on bacterial
      muropeptide structures and the relationship of structure to the biochemical
      events that the muropeptides elicit. Muropeptide sensing and recycling in both
      Gram-positive and Gram-negative bacteria are discussed, followed by muropeptide
      sensing by eukaryotes as a crucial event in the innate immune response of insects
      (via peptidoglycan-recognition proteins) and mammals (through Nod-like receptors)
      to bacterial invasion.

PMID- 22409168
TI  - Comparison of different methods to extract the required coefficient of friction
      for level walking.
AB  - The required coefficient of friction (RCOF) is an important predictor for slip
      incidents. Despite the wide use of the RCOF there is no standardised method for
      identifying the RCOF from ground reaction forces. This article presents a
      comparison of the outcomes from seven different methods, derived from those
      reported in the literature, for identifying the RCOF from the same data. While
      commonly used methods are based on a normal force threshold, percentage of stance
      phase or time from heel contact, a newly introduced hybrid method is based on a
      combination of normal force, time and direction of increase in coefficient of
      friction. Although no major differences were found with these methods in more
      than half the strikes, significant differences were found in a significant
      portion of strikes. Potential problems with some of these methods were identified
      and discussed and they appear to be overcome by the hybrid method. PRACTITIONER
      SUMMARY: No standard method exists for determining the required coefficient of
      friction (RCOF), an important predictor for slipping. In this study, RCOF values
      from a single data set, using various methods from the literature, differed
      considerably for a significant portion of strikes. A hybrid method may yield
      improved results.

PMID- 22409169
TI  - Effects of prolonged load carriage on ground reaction forces, lower limb
      kinematics and spatio-temporal parameters in female recreational hikers.
AB  - The effect of load carriage on female recreational hikers has received little
      attention. This study collected lower limb sagittal plane kinematic, spatio
      temporal and ground reaction force (GRF) data from 15 female hikers carrying four
      loads (0%, 20%, 30% and 40% body weight (BW)) over 8 km. Increasing load resulted
      in a proportional increase in GRF up to 30% BW, increased stance time, and
      greater mediolateral impulse with 30% and 40% BW. Also seen were decreased
      velocity and cadence and increased double support and knee flexion when carrying
      load compared to no load. Increased distance resulted in increased knee flexion
      and ankle plantar flexion at initial foot-ground contact. It was concluded that,
      as load mass and distance increased, female hikers modified their gait to
      attenuate the lower limb impact forces. When carrying 30% and 40% BW loads,
      however, the changes aimed at attenuating the higher GRF may result in a less
      stable gait. PRACTITIONER SUMMARY: Limited research has investigated the
      biomechanical responses of female recreational hikers to prolonged load carriage.
      This study provides a better understanding of the effects of increasing load on
      lower limb kinematics, spatio-temporal parameters and the GRF generated by female
      hikers during prolonged load carriage. The results have implications for the
      development of load carriage guidelines to minimise the risk of injury to females
      who carry backpacks and to improve performance for this population.

PMID- 22409170
TI  - Gender differences in work-related risk factors associated with low back
      symptoms.
AB  - The prevalence of low back symptoms (LBS) in many working populations is high and
      differences in prevalence between genders are inconsistent. However, gender
      specific risk factors for LBS have seldom been examined. Hence, the aim of the
      present study was to indicate gender-specific LBS risk factors. A sample of 3003
      people was interviewed by telephone to get information about current workplace
      exposure and LBS. The risk of LBS for the whole population increased with work in
      awkward/tiring positions (OR 1.37, 95% CI 1.12-1.68) and very/extremely stressful
      jobs (OR 1.46, 95% CI 1.05-2.03). None of the explanatory variables were
      significantly associated with LBS for males but working in awkward/tiring
      positions (OR 1.51, 95% CI 1.04-2.20), dissatisfaction with contact and
      cooperation with management (OR 1.68, 95% CI 1.02-2.78) and finding their job to
      be very/extremely stressful (OR 2.27, 95% CI 1.46-3.52) were significantly
      associated with LBS for females. Interventions to reduce LBS in workplaces should
      focus on reducing working in awkward/tiring positions, improving contact and
      cooperation with management, and reducing stressful jobs, especially amongst
      females. PRACTITIONER SUMMARY: Strategies to prevent or reduce LBS should focus
      on reducing exposure to awkward or tiring positions at work, improving contact
      and cooperation with management, and reducing stressful jobs, especially for
      females.

PMID- 22409171
TI  - Maximum acceptable weight of lift reflects peak lumbosacral extension moments in
      a functional capacity evaluation test using free style, stoop and squat lifting.
AB  - It is unclear whether the maximum acceptable weight of lift (MAWL), a common
      psychophysical method, reflects joint kinetics when different lifting techniques
      are employed. In a within-participants study (n = 12), participants performed
      three lifting techniques--free style, stoop and squat lifting from knee to waist
      level--using the same dynamic functional capacity evaluation lifting test to
      assess MAWL and to calculate low back and knee kinetics. We assessed which knee
      and back kinetic parameters increased with the load mass lifted, and whether the
      magnitudes of the kinetic parameters were consistent across techniques when
      lifting MAWL. MAWL was significantly different between techniques (p = 0.03). The
      peak lumbosacral extension moment met both criteria: it had the highest
      association with the load masses lifted (r > 0.9) and was most consistent between
      the three techniques when lifting MAWL (ICC = 0.87). In conclusion, MAWL reflects
      the lumbosacral extension moment across free style, stoop and squat lifting in
      healthy young males, but the relation between the load mass lifted and
      lumbosacral extension moment is different between techniques. PRACTITIONER
      SUMMARY: Tests of maximum acceptable weight of lift (MAWL) from knee to waist
      height are used to assess work capacity of individuals with low-back disorders.
      This article shows that the MAWL reflects the lumbosacral extension moment across
      free style, stoop and squat lifting in healthy young males, but the relation
      between the load mass lifted and lumbosacral extension moment is different
      between techniques. This suggests that standardisation of lifting technique used
      in tests of the MAWL would be indicated if the aim is to assess the capacity of
      the low back.

PMID- 22409172
TI  - Cost efficiency comparison of four video-based techniques for assessing upper arm
      postures.
AB  - Many video-based techniques for assessing postures at work have been developed.
      Choosing the most appropriate technique should be based on an evaluation of
      different alternatives in terms of their ability to produce posture information
      at low input costs, i.e. their cost efficiency. This study compared four video
      based techniques for assessing upper arm postures, using cost and error data from
      an investigation on hairdressers. Labour costs associated with the posture
      assessments from the video recordings were the dominant factor in the cost
      efficiency comparison. Thus, a work sampling technique associated with relatively
      large errors appeared, in general, to be the most cost-efficient because it was
      labour-saving. Measurement bias and other costs than labour cost for posture
      assessment influenced the ranking and economic evaluation of techniques, as did
      the applied measurement strategy, i.e. the numbers of video recordings and
      repeated assessments of them. PRACTITIONER SUMMARY: The cost efficiency of four
      video-based techniques for assessing upper arm postures was compared. Work
      sampling techniques were in general more cost efficient than continuous
      observations since they were labour-saving. Whilst a labour cost dominated the
      comparison, 'hidden costs', bias and measurement strategy also influenced this
      dominance.

PMID- 22409173
TI  - The effects of joint torque, pace and work:rest ratio on powered hand tool
      operations.
AB  - Repetitive use of hand-held power tools is associated with work-related upper
      extremity musculoskeletal disorders. Using a pneumatic nutrunner, 21 men
      completed twelve 360 repetitive fastener-driving sessions on three joints (hard,
      soft and control) at slow and fast pace, and two different work:rest patterns.
      Handgrip force and perceived exertions were collected throughout each session.
      For the control joint, the mean grip force exerted was 39.6% of maximum voluntary
      exertion (MVE) whereas during hard and soft joint sessions it was 48.9% MVE and
      56.9% MVE, respectively. Throughout each session, the grip force decreased, more
      while operating soft and hard joints as compared with the control joint
      (regression slope: -0.022 and -0.023, compared with -0.007 N/drive,
      respectively), suggesting considerable upper extremity muscular effort by
      participants during torque buildup. Fast work pace resulted in higher average
      grip forces by participants but a greater decrease in the force as the session
      progressed. Providing rest breaks reduced perceived exertions. The findings gain
      additional knowledge for assembly task design to possibly reduce the hand/arm
      injury risks for the operator.    Practitioner Summary: Powered hand tools are
      widely used in assembly and manufacturing industries. However, the nature of
      their repetitive use on human operator biomechanical and perceptual responses is
      not fully understood. This study examined work-related risk factors such as joint
      torque, pace and work:rest ratios on powered hand tool performance.

PMID- 22409175
TI  - Obituary. Ted Megaw.

PMID- 22409176
TI  - Ted Megaw: an appreciation.

PMID- 22409178
TI  - Editorial: Functional complementation, molecular targeted strategies, and
      chemo/immuno-sensitization in cancer treatment: hurdles and solutions.

PMID- 22409177
TI  - Integrating candidate gene and quantitative genetic approaches to understand
      variation in timing of breeding in wild tit populations.
AB  - Two commonly used techniques for estimating the effect of genes on traits in wild
      populations are the candidate gene approach and quantitative genetic analyses.
      However, whether these two approaches measure the same underlying processes
      remains unresolved. Here, we use these two methods to test whether they are
      alternative or complementary approaches to understanding genetic variation in the
      timing of reproduction - a key trait involved in adaptation to climate change -
      in wild tit populations. Our analyses of the candidate gene Clock show weak
      correlates with timing variables in blue tits, but no association in great tits,
      confirming earlier results. Quantitative genetic analyses revealed very low
      levels of both direct (female) and indirect (male) additive genetic variation in
      timing traits for both species, in contrast to previous studies on these traits,
      and much lower than generally assumed. Hence, neither method suggests strong
      genetic effects on the timing of breeding in birds, and further work should seek
      to assess the generality of these conclusions. We discuss how differences in the
      genetic control of traits, species life-history and confounding environmental
      variables may determine how useful integrating these two techniques is to
      understand the phenotypic variation in wild populations.

PMID- 22409179
TI  - Botulinum toxin A in prostate disease: a venom from bench to bed-side.
AB  - Botulinum toxin is one of the most toxic natural substances; it acts by blocking
      the neuromuscular transmission by inhibiting Acetylcholine (Ach) releasing from
      the motor nerve into the neuromuscular junction. Although the toxin inhibits ACh
      release, other transmitters can also be inhibited. Botulinum toxin, specifically
      toxin type A (BONT-A) has been used since the 1970s to treat many different
      disorders, such as general spasticity resulting from stroke, multiple sclerosis
      or cerebral palsy, strabismus, hyperhidrosis or excessive sweating, pain, and it
      is effective in combating migraine and tension headaches. Since prostate gland is
      under the influence of autonomic innervation and associated neurotransmitters,
      the effects of BONT-A on the prostate have gained attention in the urological
      community and it has been studied in different species, including rats, dogs and
      humans. The aim of this paper is to review the mechanism of action of botulinum
      toxin and to discuss in particular the results of BONT-A treatment for benign
      prostatic hyperplasia (BPH), providing perspectives on potential therapy
      according to actual knowledge.

PMID- 22409180
TI  - Constructing preference from experience: the endowment effect reflected in
      external information search.
AB  - People often attach a higher value to an object when they own it (i.e., as
      seller) compared with when they do not own it (i.e., as buyer)--a phenomenon
      known as the endowment effect. According to recent cognitive process accounts of
      the endowment effect, the effect is due to differences between sellers and buyers
      in information search. Whereas previous investigations have focused on search
      order and internal search processes (i.e., in memory), we used a sampling
      paradigm to examine differences in search termination in external search. We
      asked participants to indicate selling and buying prices for monetary lotteries
      in a within-subject design. In an experience condition, participants had to learn
      about the possible outcomes and probabilities of the lotteries by experiential
      sampling. As hypothesized, sellers tended to terminate search after sampling high
      outcomes, whereas buyers tended to terminate search after sampling low outcomes.
      These differences in stopping behavior translated into samples of the lotteries
      that were differentially distorted for sellers and buyers; the amount of the
      distortion was predictive of the resulting size of the endowment effect. In
      addition, for sellers search was more extended when high outcomes were rare
      compared with when low outcomes were rare. Our results add to the increasing
      evidence that the endowment effect is due, in part, to differences in
      predecisional information search.

PMID- 22409181
TI  - A role for self-referential processing in tasks requiring participants to imagine
      survival on the savannah.
AB  - This paper examines the role of self-reference as a possible mechanism underlying
      the superior recall found with survival processing. I suggest that previous
      failures to find comparable recall with self-referential encoding may be due to
      neglecting to ensure that task instructions require episodic retrieval. The
      studies reported herein show that when instructions explicitly request episodic
      retrieval, self-referential processing promotes recall that is statistically
      equivalent to that found with survival processing tasks. I conclude that the role
      of self-referential processing remains a viable component of the excellent memory
      produced by survival encoding instructions.

PMID- 22409182
TI  - Directed forgetting and directed remembering in visual working memory.
AB  - A defining characteristic of visual working memory is its limited capacity. This
      means that it is crucial to maintain only the most relevant information in visual
      working memory. However, empirical research is mixed as to whether it is possible
      to selectively maintain a subset of the information previously encoded into
      visual working memory. Here we examined the ability of participants to use cues
      to either forget or remember a subset of the information already stored in visual
      working memory. In Experiment 1, participants were cued to either forget or
      remember 1 of 2 groups of colored squares during a change-detection task. We
      found that both types of cues aided performance in the visual working memory task
      but that observers benefited more from a cue to remember than a cue to forget a
      subset of the objects. In Experiment 2, we show that the previous findings, which
      indicated that directed-forgetting cues are ineffective, were likely due to the
      presence of invalid cues that appeared to cause observers to disregard such cues
      as unreliable. In Experiment 3, we recorded event-related potentials and show
      that an electrophysiological index of focused maintenance is elicited by cues
      that indicate which subset of information in visual working memory needs to be
      remembered, ruling out alternative explanations of the behavioral effects of
      retention-interval cues. The present findings demonstrate that observers can
      focus maintenance mechanisms on specific objects in visual working memory based
      on cues indicating future task relevance.

PMID- 22409183
TI  - Inhibiting CD164 expression in colon cancer cell line HCT116 leads to reduced
      cancer cell proliferation, mobility, and metastasis in vitro and in vivo.
AB  - BACKGROUND: CD164 (Endolyn) is a sialomucin, which has been found to play roles
      in regulating proliferation, adhesion, and differentiation of hematopoietic stem
      cells. Possible association of CD164 with solid cancer development remains
      unknown. METHODS AND RESULTS: We first studied CD164 expression in biopsies from
      colorectal cancer, breast, and ovary cancer patients by semi-quantitative
      immunohistochemistry, and found that CD164 was strongly expressed in all the
      colorectal cancer samples compared to the matching normal colon tissues. The
      possible roles of CD164 in colon cancer development were further investigated
      using a well-established human colon cancer cell line HCT116. We found that
      knockdown of CD164 expression in HCT116 cells significantly inhibited cell
      proliferation, mobility, and metastasis in vitro and in vivo. The knockdown of
      CD164 expression was associated with decreased chemokine receptor CXCR4
      expression HCT116 cell surface and immunoprecipitation studies showed that CD164
      formed complexes with CXCR4. CONCLUSIONS: CD164 is highly expressed in the colon
      cancer sites, and it promotes HCT116 colon cancer cell proliferation and
      metastasis both in vitro and in vivo, and the effects may act through regulating
      CXCR4 signaling pathway. Therefore, CD164 may be a new target for diagnosis and
      treatment for colon cancer.

PMID- 22409184
TI  - The value of medical education research in Saudi Arabia.

PMID- 22409185
TI  - Effect of students' learning styles on classroom performance in problem-based
      learning.
AB  - INTRODUCTION: Since problem-based learning (PBL) sessions require a combination
      of active discussion, group interaction, and inductive and reflective thinking,
      students with different learning styles can be expected to perform differently in
      the PBL sessions. METHODOLOGY: Using "Learning Style Inventory Questionnaire,"
      students were divided into separate active and reflective learner groups. Tutors
      were asked to observe and assess the students' behavioral performance during the
      PBL sessions for a period of 5 weeks. A questionnaire of 24 items was developed
      to assess students' behavioral performance in PBL sessions. RESULTS: Active
      students tended to use multiple activities to obtain the needed information were
      more adjusted to the group norms and regulation and more skillful in using
      reasoning and problem-solving skills and in participation in discussion. On the
      other hand, reflective students used independent study more, listened actively
      and carefully to others and used previously acquired information in the
      discussion more frequently. Formative assessment quizzes did not indicate better
      performance of either group. There were no significant gender differences in PBL
      behavioral performance or quizzes' scores. CONCLUSION: Active and reflective
      learners differ in PBL class behavioral performance but not in the formative
      assessment. We recommend that students should be informed about their learning
      style and that they should learn strategies to compensate for any lacks in PBL
      sessions through self-study. Also, educational planners should ensure an adequate
      mix of students with different learning styles in the PBL groups to achieve PBL
      desired objectives.

PMID- 22409186
TI  - Supporting traditional PBL with online discussion forums: a study from Qassim
      Medical School.
AB  - BACKGROUND: The Qassim Medical School first year curriculum includes a 5-week
      problem-based learning (PBL) block. Student evaluation has highlighted inadequate
      feedback and lack of student-student and student-tutor interactions. An online
      intervention may alleviate this. METHODOLOGY: For each problem, a discussion
      forum (DF) was created with 14 threads (one for each group) in virtual PBL rooms.
      Students' and tutors' perceived satisfaction of the intervention was evaluated
      and types of posts were classified. RESULTS: By the end of the block, all
      academic staff involved and 123 students (95%) had participated in the DFs. There
      were around 2800 posts and 28,500 views. All 14 tutors and 102 (78%) students
      completed the online questionnaire. Of the students, 66 (76%) male and 36 (92%)
      female students responded. Overall, both students and tutors perceived the
      intervention positively. Posts included: reforming and finalizing learning
      objectives, posting the concept map constructed in the face-to-face session and
      questioning, encouraging and motivating each other. In addition, posts included
      tutors' feedback and redirection. CONCLUSIONS: Blending e-learning with
      conventional PBL may help overcome student-perceived shortcomings of conventional
      PBL and improve the learning experience, making learning more interactive and
      interesting.

PMID- 22409187
TI  - Using DREEM to compare graduating students' perceptions of learning environments
      at medical schools adopting contrasting educational strategies.
AB  - BACKGROUND: In response to growing concerns about conventional modes of teaching
      and learning in medicine, some medical schools in Saudi Arabia have converted to
      hybrid problem-based learning (PBL) curricula while others continue to implement
      traditional discipline-based curricula. Understanding students' perceptions of
      traditional versus PBL learning environments can be helpful for evaluating
      program strengths and weaknesses and should promote curriculum development. AIM:
      The purpose of this study was therefore to evaluate the educational environments
      of two medical schools in Riyadh, Saudi Arabia from perspectives of graduating
      medical students using the Dundee Ready Education Environment Measure (DREEM)
      inventory. RESULTS: Compared to medical school implementing a hybrid PBL
      curriculum, the overall score on the inventory for the conventional school was
      statistically significantly less (p < 0.001). In addition, students experiencing
      the hybrid-PBL curriculum held significantly higher perceptions in the learning,
      academic self-perception and atmosphere sub-domains of the inventory (p < 0.001).
      Overall, our results align with previous studies pertaining to DREEM scores of
      other regional conventional and international PBL medical schools. CONCLUSION: We
      conclude that applying DREEM as a diagnostic tool provides important insights and
      understanding of learning environments where different educational strategies are
      adopted and which may be in need of development and change. Implications for
      curriculum development and improvement of learning environments in health
      professions education institutions are discussed.

PMID- 22409188
TI  - The prevalence and correlates of depressive symptoms from an Arabian setting: a
      wake up call.
AB  - It has been shown that medical students have a higher rate of depressive symptoms
      than the general population and age- and sex-matched peers. This study aimed to
      estimate the prevalence of depressive symptoms among the medical students of a
      large school following a traditional curriculum and its relation to personal
      background variables. A descriptive-analytic, cross-sectional study was conducted
      in a medical school in Riyadh, Saudi Arabia. The medical students of King Saud
      University in Riyadh, Saudi Arabia, were screened for depressive symptoms using
      the 21-item Beck Depression Inventory. A high prevalence of depressive symptoms
      (48.2%) was found, it was either mild (21%), moderate (17%), or severe (11%). The
      presence and severity of depressive symptoms had a statistically significant
      association with early academic years (p < 0.000) and female gender (p < 0.002).
      The high prevalence of depressive symptoms is an alarming sign and calls for
      remedial action, particularly for the junior and female students.

PMID- 22409189
TI  - Sleep disorder among medical students: relationship to their academic
      performance.
AB  - BACKGROUND: Medical students are exposed to a significant level of pressure due
      to academic demands. Their sleep pattern is characterized by insufficient sleep
      duration, delayed sleep onset, and occurrence of napping episodes during the day.
      OBJECTIVE: To examine the prevalence of sleep disorder among medical students and
      investigate any relationship between sleep disorder and academic performance.
      METHODS: This is a cross-sectional self-administered questionnaire-based study.
      The participants were medical students of the first, second, and third academic
      years. The Epworth Sleepiness Scale (ESS) was also included to identify sleep
      disorder and grade point average was recorded for academic performance. RESULTS:
      There were 491 responses with a response rate of 55%. The ESS score demonstrated
      that 36.6% of participants were considered to have abnormal sleep habits, with a
      statistically significant increase in female students (p = 0.000). Sleeping
      between 6-10 h per day was associated with normal ESS scores (p = 0.019) as well
      as the academic grades >= 3.75. Abnormal ESS scores were associated with lower
      academic achievement (p = 0.002). CONCLUSION: A high prevalence of sleep disorder
      was found in this group of students, specifically female students. Analysis of
      the relationship between sleep disorder and academic performance indicates a
      significant relationship between abnormal ESS scores, total sleeping hours, and
      academic performance.

PMID- 22409190
TI  - Medical education in Saudi Arabia: an exciting journey.

PMID- 22409191
TI  - Exploring assessment factors contributing to students' study strategies:
      literature review.
AB  - "Assessment steers students' learning" is a statement that has been used
      repeatedly without solid evidence in the literature. This manuscript aims to
      evaluate the published literatures on the effect of teaching learning environment
      in particular, the implemented assessment on students' learning approaches. A
      literature review was performed on the effect of assessment on students learning
      approaches. English language literatures were searched in Pubmed, PsycINFO, and
      Medline without restriction to type or date of publication. Reviewing the
      literature, the most prominent identified theme was assessment function
      characterized in summative and formative assessment and general effect of
      assessment on students' learning approaches. The literature review has pointed
      clearly to the complexity of the relationship between learning environment,
      students' perceptions of assessment demands, and students' approaches to
      learning. Many factors (extrinsic and intrinsic) were theoretically proposed to
      mediate students' approaches to learning in response to their assessment.
      However, few of these factors were researched in the published literature.
      Formative assessment is likely to contribute to students' deep approach to
      learning while summative is likely to contribute to their surface approach.
      However, these effects are not definite and further research about the complex
      relationship between assessment and students' learning is required.

PMID- 22409192
TI  - Specialty preferences: trends and perceptions among Saudi undergraduate medical
      students.
AB  - BACKGROUND: The exploration of specialty choices by medical students is a hot
      debate as it affects several important determinants of health care delivery. This
      study was carried out to determine variation in specialty preferences during
      medical school training and the perceptions that affect students' specialty
      choice. METHODS: A cross-sectional questionnaire-based study was performed on 590
      students with a 93.22% response rate and covered queries on demography, specialty
      choices, and perceptions influencing specialty choices. Class-wise analysis of
      specialty choices was carried out. RESULTS: The most preferred specialty
      expressed by male students was surgery, followed by internal medicine and
      orthopedics, while most preferred by female students were surgery, followed by
      pediatrics and ophthalmology. Male students' emphasized factors like less
      competitive field, shortage of specialists, and diversity of patients while the
      prestige of specialty and teaching opportunities had a greater impact on female
      students. CONCLUSIONS: Surgery, internal medicine, pediatrics, orthopedics, and
      ophthalmology were the most preferred specialty choices. Gender preference was
      observed to affect choices of few specialties such as orthopedics and
      obstetrics/gynecology. Perceptions which have an impact on specialty selection of
      male and female students may reflect a different tempo of growing up in men and
      women.

PMID- 22409193
TI  - Development and evaluation of study guide template for an integrated
      cardiovascular module.
AB  - The undergraduate medical curriculum in the King Abdulaziz University in Jeddah,
      Saudi Arabia, was reformed in 2002. It is integrated, organized in courses and
      modules, and has an increasing proportion of problem-based and self-directed
      learning. The new curriculum has presented the faculty and students with specific
      challenges. Accustomed to a traditional teacher-centred approach, and because the
      language of instruction is English, students needed much more support and
      encouragement in taking advantages of independent learning than their western
      counterparts would require. A well-designed study guide may be more effective
      student learning tool in the new integrated curriculum. This article describes to
      simplify and modern approach to the production of study guides. The approach is
      based on the development and the use of a study guide template. The guide is
      evaluated by second year medical students at King Abdulaziz University. The study
      guide is highly appreciated by student evaluations and 'study guide template'
      that includes a well-designed layout is a useful aid for medical teachers who
      have had no experience in producing a study guide. The template allows medical
      teachers to invest their time in the production of the content rather than in the
      layout and format of the guide.

PMID- 22409194
TI  - Faculty development program: a guide for medical schools in Arabian Gulf (GCC)
      countries.
AB  - The effective faculty development (FD) program is the most essential component
      for creating successful educational innovation. The purpose of having any FD
      program is to enable faculty to accomplish their goals, and through accomplishing
      these goals, the missions of their departments, colleges, and universities would
      be accomplished. FD programs will need to provide an extensive set of
      developmental-educational skills and strategies in order to serve faculty members
      who come from various disciplines and at different stages of their careers, have
      different faculty responsibilities, backgrounds, appointments, and bring unique
      personal circumstances to their work. Although, there are quite a large number of
      medical schools in Arabian Gulf (GCC) countries, still the FD programs are
      extremely lacking. To analyze the situation in Gulf medical schools with regards
      to FD programs, we would emphasize the following needs: (1) FD committees or
      departments; (2) formal programs in FD for new or junior and for also senior and
      established faculty members; and (3) funding support has to be devoted to improve
      the skills of faculty members in academia. This aimed at presenting a proposed FD
      program to be considered as a tool for qualitative improvement in medical schools
      of GCC countries.

PMID- 22409195
TI  - Evaluating a masters of medical education program: attaining minimum quality
      standards?
AB  - BACKGROUND: As more Masters of Medical Education programs (MMEPs) become
      available, the quality of these programs will be under increased scrutiny. AIMS:
      We applied World Federation for Medical Education (WFME) quality standards in an
      internal evaluation process involving participants and faculty to determine: (i)
      if our MMEP met minimum quality standards (ii) if WFME standards provided a
      useful framework to evaluate minimum standards in our context and (iii) whether
      the program was perceived as developing future educational leaders. METHODS: A
      cross-sectional researcher developed survey, interviews and secondary data
      analysis were utilized for data collection. Quantitative data were analyzed using
      SPSS version 16. Descriptive statistics were generated. Fisher's exact test
      determined statistically significant differences between groups. Qualitative data
      were analyzed using a framework analysis. RESULTS: All students attending the
      MMEP 2007-2010 (n = 67) and faculty (n = 11) were invited to participate; 48%
      students and 91% faculty responded. Quantitative and qualitative results
      demonstrated positive perspectives regarding all three aspects of our enquiry.
      Nevertheless, needed improvements were identified in the areas of availability of
      human and physical resources, feedback and aspects of the research experience.
      CONCLUSIONS: Impact on quality of health professions education in the Kingdom and
      participant educational leadership development are particularly important social
      responsiveness features of the program. Refinement of the evaluation instrument
      and WFME standards to ensure clarity and relevance to local contexts as well as a
      future expected imperative to move beyond social responsiveness to social
      accountability in health professions education, are future challenges discussed.

PMID- 22409196
TI  - A matter of degrees: the introduction of clinical doctorates to the Saudi higher
      education system and a comparative prospective from the American model.
AB  - Recent unprecedented growth in Saudi population challenged its infrastructure and
      intensified demand for higher education and healthcare. In response, both the
      government and the private sector founded numerous colleges and universities,
      increasing the overall number from 8 to 49 institutions of higher education. A
      significant portion of the expansion has been in the health professions higher
      education, which also included the establishment of new teaching hospitals and
      other medical training facilities. As part of this growth, practice (clinical)
      doctorates have conspicuously made their presence felt in Saudi Arabia. The
      doctor of pharmacy is the first clinical doctorate that has been formally adopted
      as the terminal professional degree in the field. Others are in the works.
      Results are presented using descriptive methods. Data were collected from reviews
      of the literature and individual institutional websites of Saudi colleges,
      universities and salient governmental regulatory and national accrediting
      agencies. This article will introduce clinical doctorates, their status and state
      of implementation in the American health professions higher education system as a
      possible model. The article will review the current status of clinical
      doctorates' implementation in Saudi Arabia. It will conclude with a
      recommendation for concerned stake holders, including policy makers, educators,
      and practitioners.

PMID- 22409197
TI  - Evaluation of Saudi family medicine training program: the application of CIPP
      evaluation format.
AB  - The Saudi Diploma in Family Medicine (SDFM) was enacted in 2007 to fulfill the
      needs of qualified Primary Health Care providers in Saudi Arabia. Evaluation is
      not only an integral process for designing educational training programs, but an
      effective evaluation strategy that helps achieve program objectives and enhances
      the quality of learning objectives: (1) Construct a self-administered
      questionnaire based on Context, input, process and product (CIPP) format to seek
      trainees' perceptions about the SDFM program; (2) identify the strengths and
      weaknesses of the SDFM program in relation to the learning outcomes; and (3)
      define the main obstacles to achieve the outcomes. A self-administered
      questionnaire was designed based on the CIPP evaluation format after. its
      validity and reliability were tested through piloting. Then, all the SDFM program
      trainees were included. The study response rate was 91.2%. More than 77% of the
      trainees stated that they had achieved the program objectives; a significant
      difference was found among Saudis and non-Saudis (p = 0.002). The training period
      was reported by 84% as a main barrier to achieve the program objectives,
      particularly the hospital rotation period. Results indicate an overall
      satisfaction with the training objectives and the teaching methods used. These
      findings can be useful for the policy makers to implement the suggested
      recommendations and deal with obstacles to improve the SDFM program in order to
      provide effective and efficient primary care services.

PMID- 22409198
TI  - How medical professionalism is conceptualised in Arabian context: a validation
      study.
AB  - Professionalism has been increasingly recognised as an explicit component of
      medical education, especially in the western world. Professionalism is culture
      sensitive. Few efforts have been made to conceptualise professionalism in
      relation to the Arabian context. The aim of this study is to validate the
      components of professionalism framework of the American Board of Internal
      Medicine (ABIM) to the Arabian context. The authors invited a heterogeneous group
      of native Arab health professionals and academics to contribute to a reference
      panel. They represented a variety of disciplines, and seniority levels, and from
      different healthcare institutions and medical schools in Egypt, Saudi Arabia and
      United Arab Emirates. They were queried about their perception of the importance
      of each domain of professionalism as proposed by the ABIM, and were encouraged to
      suggest new domains if they thought it necessary. Thirty two out of the 45
      invited health professionals and educators (71%) contributed to the reference
      panel. The panel confirmed the appropriateness of the six ABIM domains to the
      Arabian context, and further proposed the Autonomy of professionals as an
      additional domain. The modified framework, based on ABIM domains, demonstrated
      the Arabian conceptualisation of professionalism.

PMID- 22409199
TI  - Preparation and irradiation of Pluronic F127-based thermoreversible and
      mucoadhesive hydrogel for local delivery of naproxen.
AB  - To improve physical properties and modulate the mucoadhesive hydrogel formulation
      via cross-linking by radiation, hydrogels were prepared using thermoreversible
      polymer Pluronic F127 (PF127) and mucoadhesive polymer carbopol 934P (C934P). As
      a model drug, naproxen was loaded in the hydrogel formulation. Sol-gel transition
      temperatures of hydrogels were measured by the tube-inversion method. The
      mucoadhesive potential of each formulation was determined by measuring the force
      required to detach the formulation from oral mucosal tissue. To strengthen the
      mechanical properties, the formulations were irradiated using an electronic beam.
      Drug release from the hydrogels and the cytotoxicity of each formulation were
      investigated. Sol-gel transition temperatures of the formulations were decreased
      by the addition of carbopol and were close to body temperature. The mucoadhesive
      force of the PF127 formulation was increased by addition of carbopol. In vitro
      release was sustained and the release rate was reduced by the addition of
      carbopol. After irradiation, the mucoadhesive force was increased about five-fold
      especially in the case of PF127 23% (9.7 kPa) and in vitro release was not
      sustained further. In conclusion, the use of a PF127 formulation incorporating a
      mucoadhesive polymer could effectively and safely improve oral residence time and
      absorption of naproxen. Irradiated formulations showed permanent cross-linking
      and improved properties. 

PMID- 22409200
TI  - Electrothermal supercharging of proteins in native electrospray ionization.
AB  - The formation of high charge-state protein ions with nanoelectrospray ionization
      (nESI) from purely aqueous ammonium bicarbonate solutions at neutral pH, where
      the proteins have native or native-like conformations prior to ESI droplet
      formation, is demonstrated. This "electrothermal" supercharging method depends on
      the temperature of the instrument entrance capillary, the nESI spray potential,
      and the solution ionic strength and buffer, although other factors almost
      certainly contribute. Mass spectra obtained with electrothermal supercharging
      appear similar to those obtained from denaturing solutions where charging beyond
      the total number of basic sites can be achieved. For example, a 17+ ion of bovine
      ubiquitin was formed by nESI of a 100 mM ammonium bicarbonate, pH 7.0, solution,
      which is three more charges than the total number of basic amino acids plus the N
      terminus. Heating of the ESI droplets in the vacuum/atmosphere interface and the
      concomitant denaturation of the protein in the ESI droplets prior to ion
      formation appears to be the primary origin of the very high charge-state ions
      formed from these purely aqueous, buffered solutions. nESI mass spectra
      resembling those obtained under traditional native or denaturing conditions can
      be reversibly obtained simply by toggling the spray voltage between low and high
      values.

PMID- 22409202
TI  - Measuring patient satisfaction changes patient satisfaction.

PMID- 22409201
TI  - On the morphology of viral capsids: elastic properties and buckling transitions.
AB  - The morphology of icosahedral viruses ranges from highly spherical to highly
      faceted, and for some viruses a shape transition occurs during the viral life
      cycle. This phenomena is predicted from continuum elasticity, via the buckling
      transition theory by Nelson (Phys. Rev. E 2003, 68, 051910), in which the shape
      is dependent on the Foppl-von Karman number (gamma), which is a ratio of the two
      dimensional Young's modulus (Y) and the bending modulus (kappa). However, until
      now, no direct calculations have been performed on atomic-level capsid structures
      to test the predictions of the theory. In this study, we employ a previously
      described multiscale method by May and Brooks (Phys. Rev. Lett. 2011, 106,
      188101) to calculate Y and kappa for the bacteriophage HK97, which undergoes a
      spherical to faceted transition during its viral life cycle. We observe a change
      in gamma consistent with the buckling transition theory and also a significant
      reduction in kappa, which facilitates formation of the faceted state. We go on to
      examine many capsids from the T = 3 and 7 classes using only elastic network
      models, which allows us to calculate the ratio Y/kappa, without the expense of
      all-atom molecular dynamics. We observe for the T = 7 capsids, there is strong
      correlation between the shape of the capsid and gamma; however, there is no such
      correlation for the smaller T = 3 viruses.

PMID- 22409203
TI  - Eighteen years of continuously sustained elimination of iodine deficiency in the
      Islamic Republic of Iran: the vitality of periodic monitoring.
AB  - BACKGROUND: Two decades ago the Islamic Republic of Iran was among countries most
      severely affected by iodine deficiency. Iran has since achieved great success in
      the control and elimination of iodine deficiency disorders (IDDs) following the
      national salt iodization program, initiated in 1989. The aim of the study was to
      evaluate the effectiveness of sustained consumption of iodized salt by Iranian
      households and the current status of iodine nutrition in all 30 provinces of
      Iran. METHODS: Goiters-measured by palpation-and urinary iodine concentration of
      children were assessed. In this descriptive cross-sectional study, 36,000
      schoolchildren (18,000 girls and 18,000 boys), aged 8-10 years, were randomly
      selected, from October 2007 to February 2008, from 30 provinces of the country.
      Goiter prevalence and urinary iodine excretion in schoolchildren and the iodine
      content of salt at household, factory, and distribution site levels were
      measured. RESULTS: The goiter rate in the country was 6.5% (6% grade 1 and 0.5%
      grade 2), and the weighted goiter rate was 5.7%. The total goiter rate in
      Hamedan, Zanjan, Kermanshah, Mazandaran, and Gilan provinces was over 10%. The
      median urinary iodine was 140 MUg/L. Urinary iodine levels of 20-50, 50-99, and
      >=100 MUg/L were noted in 15.3%, 19.8%, and 64.9% of the samples, respectively.
      In four provinces, the median urinary iodine was lower than 100 MUg/L. The mean
      (+/-SD) and median salt iodine values were 23.2 (+/-13.8) and 34.7 ppm,
      respectively, at the production level, and 32.4 (+/-14.7) and 32.3 ppm,
      respectively, at the distribution level. Ninety-eight percent of households
      consumed iodized salt, 58% of households had appropriate salt storage, and 27% of
      the household salts contained <20 ppm. CONCLUSIONS: Iran has achieved much in the
      development of universal salt iodization strategy and elimination of IDDs and
      currently meets all criteria for sustainable elimination of iodine deficiency.
      However, the lack of adequate iodine nutrition in some provinces necessitates
      special attention and proper monitoring.

PMID- 22409205
TI  - Termination of psychodynamic psychotherapy with adolescents: A review and
      contemporary perspective.
AB  - In psychodynamic psychotherapy with adolescents, termination-the phase of
      treatment during which the patient and his or her parents end a therapeutic
      relationship with a therapist-has received limited attention in the extant
      literature. Despite this oversight, termination is of critical clinical
      importance. This phase of psychotherapy with adolescents is heralded by the
      integration and consolidation of progress, relational changes, and the
      relinquishing of the symptoms that brought the adolescent to treatment. Herein,
      the relevant literature surrounding termination in psychodynamic
      psychotherapeutic work with adolescents will be reviewed. Important aspects of
      termination will be highlighted and discussed, including (1) criteria for
      termination, (2) techniques for working with parents, (3) "forced terminations,"
      (4) countertransference, and (5) common complications that arise during this
      phase of treatment. Finally, the complexities of the termination process as well
      as recent contributions to our understanding of this critically important process
      from attachment theory and intersubjectivity will be illustrated with clinical
      material.

PMID- 22409204
TI  - Key stakeholder perceptions regarding acute care psychiatry in distressed
      publicly funded mental health care markets.
AB  - The role of acute care inpatient psychiatry, public and private, has changed
      dramatically since the 1960s, especially as recent market forces affecting the
      private sector have had ripple effects on publicly funded mental health care. Key
      stakeholders' experiences, perceptions, and opinions regarding the role of acute
      care psychiatry in distressed markets of publicly funded mental health care were
      examined. A qualitative research study was conducted using semi-structured
      thematic interviews with 52 senior mental health system administrators, clinical
      directors and managers, and nonclinical policy specialists. Participants were
      selected from markets in six regions of the United States that experienced recent
      significant closures of acute care psychiatric beds. Qualitative data analyses
      yielded findings that clustered around three sets of higher order themes:
      structure of care, service delivery barriers, and outcomes. Structure of care
      suggests that acute care psychiatry is seen as part of a continuum of services;
      service delivery barriers inhibit effective delivery of services and are
      perceived to include economic, regulatory, and political factors; outcomes
      include fragmentation of mental health care services across the continuum, the
      shift of mental health care to the criminal justice system, and market-specific
      issues affecting mental health care. Findings delineate key stakeholders'
      perceptions regarding the role acute care psychiatry plays in the continuum of
      care for publicly funded mental health and suggest that public mental health care
      is inefficacious. Results carry implications for policy makers regarding
      strategies/policies to improve optimal utilization of scarce resources for mental
      health care, including greater focus on psychotherapy.

PMID- 22409206
TI  - A novel methodology for identifying emerging themes in small group dynamics.
AB  - An understanding of group dynamics, such as the dynamics in family psychotherapy,
      is of great importance to mental health practitioners and other experts who seek
      to understand the group as a working whole. In this context, identifying themes
      emerging from the dynamics is of prime importance. However, the lack of formal
      tools makes it difficult to validly identify emerging themes. The current article
      presents a novel methodology for identifying themes emerging from group dynamics.
      With this methodology, the verbal utterances of group members are automatically
      analyzed to produce a "group matrix." Motifs that emerge in the complex network
      of signs that is generated by the group are analyzed by means of a computer
      program, and the explanatory value of the identified motifs is elaborated. The
      methodology and its benefits are presented and illustrated through the analysis
      of (1) the family dynamics in a literary piece, Tennessee Williams's The Glass
      Menagerie and (2) the group dynamics of Israeli and Palestinian participants
      discussing the notion of forgiveness.

PMID- 22409207
TI  - Psychodynamic psychotherapy for posttraumatic stress disorder related to
      childhood abuse--Principles for a treatment manual.
AB  - In this article, the authors present a psychodynamically oriented psychotherapy
      approach for posttraumatic stress disorder (PTSD) related to childhood abuse.
      This neurobiologically informed, phase-oriented treatment approach, which has
      been developed in Germany during the past 20 years, takes into account the broad
      comorbidity and the large degree of ego-function impairment typically found in
      these patients. Based on a psychodynamic relationship orientation, this treatment
      integrates a variety of trauma-specific imaginative and resource-oriented
      techniques. The approach places major emphasis on the prevention of vicarious
      traumatization. The authors are presently planning to test the approach in a
      randomized controlled trial aimed at strengthening the evidence base for
      psychodynamic psychotherapy in PTSD.

PMID- 22409209
TI  - Photoisomerization and relaxation dynamics of a structurally modified biomimetic
      photoswitch.
AB  - Recent experimental and theoretical studies on N-alkylated indanylidene pyrroline
      Schiff bases (NAIP) show that these compounds exhibit biomimetic
      photoisomerization analogous to that in the chromophore of rhodopsin. The NAIP
      compounds studied previously isomerize rapidly and often evolve coherently on the
      ground-electronic surface after reaction. We present the results of transient
      electronic absorption spectroscopy on dMe-OMe-NAIP, a newly synthesized NAIP
      analogue that differs from other NAIP compounds in the substituents on its
      pyrrolinium ring. Following excitation with 400 nm light, dMe-OMe-NAIP relaxes
      from the electronic-excited state in less than 500 fs, which is slower than in
      other analogues, and does not show the prominent oscillations observed in other
      NAIP compounds. A reduction in the amount of twisting between the rings caused by
      removal of the methyl group is likely responsible for the slower isomerization.
      Measurements in solvents of varying viscosity and structure suggest that
      intramolecular processes dominate the relaxation of nascent photoproducts.

PMID- 22409210
TI  - Computer programs to estimate overoptimism in measures of discrimination for
      predicting the risk of cardiovascular diseases.
AB  - BACKGROUND: Development of chronic disease risk prediction models has become a
      growing area of research in recent years. The internal validity of such models is
      sometimes lower than estimated from the development sample. Overfitting or
      overoptimism of the developed model and/or differences between the samples are
      likely causes for this. For modelling of an uncommon outcome, bootstrapping for
      overoptimism is the preferred method for afterwards shrinking of regression
      coefficients and the model's discrimination and calibration for overoptimism.
      However, computer programs for different types of bootstrap validation are not
      readily available. We developed two SAS macro programs--one for the simple
      bootstrap that compares the discriminatory performance of the Cox proportional
      hazards model from the original sample in bootstrap samples; and another (which
      is more efficient), known as stepwise bootstrap validation, that makes the same
      comparison but from models developed by variable selection from bootstrap samples
      in the original sample. These are illustrated through an example from
      cardiovascular disease (CVD) risk prediction. METHODS: Two SAS macro programs for
      Cox proportional hazards model using Proc PHREG were developed for estimating
      overoptimism in Harrell's C and Somers' D statistics. The computer programs were
      applied to data on CVD incidence for a Framingham cohort that combined both the
      original and offspring exams. The risk factors considered were current smoking,
      diabetes, age, sex, systolic blood pressure, diastolic blood pressure, total
      cholesterol, high-density lipoprotein cholesterol, triglycerides and body mass
      index. RESULTS: The degree of overoptimism in both Harrell's C and Somers' D
      statistics were low. Both these statistics were corrected for overoptimism by
      subtracting overoptimism from their observed values. Between the two bootstrap
      validation algorithms, the degree of overoptimism was estimated to be higher for
      stepwise bootstrap validation. CONCLUSION: The programs are very useful for
      evaluating the 'overoptimism corrected' predictive performance of Cox
      proportional hazards model.

PMID- 22409211
TI  - Heart rate-lowering efficacy and respiratory safety of ivabradine in patients
      with obstructive airway disease: a randomized, double-blind, placebo-controlled,
      crossover study.
AB  - BACKGROUND: There is substantial evidence that heart rate (HR) is a powerful
      predictor of mortality in both normal individuals and in patients with
      cardiovascular disease. The use of beta-adrenoceptor antagonists (beta-blockers)
      has confirmed the importance of lowering elevated HR in a patient's prognosis.
      However, these agents can have undesirable adverse effects (AEs) and due to the
      risk of bronchoconstriction are contraindicated in patients with obstructive
      airway disease. A selective bradycardic agent, without such undesirable effects,
      could be of therapeutic interest. Ivabradine, a new I(f) inhibitor that acts
      specifically on the sino-atrial node, is a pure HR-lowering agent. OBJECTIVE: The
      objective of this study was to assess HR-lowering efficacy and respiratory safety
      of ivabradine in patients with asthma and chronic obstructive pulmonary disease
      (COPD). METHODS: This was a randomized, single-center, double-blind, placebo
      controlled, crossover trial. Enrolment began in May 2009, and the last patient
      completed the study in January 2011. The study was conducted in an ambulatory
      setting. A total of 40 patients completed the study (20 asthmatic patients and 20
      COPD patients). Inclusion criteria were: documented diagnosis of asthma or COPD
      according to international guidelines, age 18-75 years, and mean HR on Holter ECG
      recording of >=60 beats/min. Exclusion criteria included disease exacerbation in
      a previous month or inability to understand instructions on the study procedures.
      All patients received ivabradine 7.5 mg twice daily for 5 days and placebo twice
      daily for 5 days in a crossover manner, in one of the two arms of the study, with
      at least 2 days of washout between treatments. The main outcome measures included
      the difference in HR between ivabradine and placebo treatment and change in HR in
      comparison with baseline. Other evaluated outcomes were differences in the peak
      expiratory flow rate (PEFR), the daily symptom score, rescue medication
      consumption, and AEs. RESULTS: Ivabradine produced significantly lower mean HR
      than placebo in both groups of patients: asthma 67.4 +/- 8.38 versus 82.85 +/-
      11.19 beats/min (p < 0.001) and COPD 69.75 +/- 8.9 versus 81.05 +/- 9.75
      beats/min (p < 0.001). Similar results were observed for the minimal HR as well
      as for the maximal noted HR. In comparision with baseline, ivabradine
      significantly reduced HR in both groups of studied patients (all p < 0.05),
      whereas placebo did not have such an effect. No significant difference, in either
      the asthma or the COPD group, was found between ivabradine and placebo in morning
      and evening peak expiratory flow rate, peak expiratory flow diurnal variability,
      daily symptom scores, and rescue medication usage (all p > 0.05). Both treatments
      were well tolerated. The incidence of AEs was low and generally similar in both
      periods of treatment, except for visual symptoms during treatment with
      ivabradine, which was reported by 5% of the patients. CONCLUSION: Our study
      demonstrated that selective HR reduction with ivabradine is effective in patients
      with asthma and COPD, with no alteration in respiratory function or symptoms over
      the duration of the study. Ivabradine offers an interesting alternative, as an HR
      lowering agent, in patients with respiratory disease and contraindications to
      beta-blockers. CLINICAL TRIAL REGISTRATION: Registered at www.clinicaltrials.gov
      (NCT01365286).

PMID- 22409212
TI  - Qualitative and quantitative characterization of volatile organic compound
      emissions from cut grass.
AB  - Mechanical wounding of plants triggers the release of a blend of reactive
      biogenic volatile organic compounds (BVOCs). During and after mowing and
      harvesting of managed grasslands, significant BVOC emissions have the potential
      to alter the physical and chemical properties of the atmosphere and lead to ozone
      and aerosol formation with consequences for regional air quality. We show that
      the amount and composition of BVOCs emitted per unit dry weight of plant material
      is comparable between laboratory enclosure measurements of artificially severed
      grassland plant species and in situ ecosystem-scale flux measurements above a
      temperate mountain grassland during and after periodic mowing and harvesting. The
      investigated grassland ecosystem emitted annually up to 130 mg carbon m(-2) in
      response to cutting and drying, the largest part being consistently represented
      by methanol and a blend of green leaf volatiles (GLV). In addition, we report the
      plant species-specific emission of furfural, terpenoid-like compounds (e.g.,
      camphor), and sesquiterpenes from cut plant material, which may be used as
      tracers for the presence of given plant species in the ecosystem.

PMID- 22409213
TI  - Phylogeography of the Cape velvet worm (Onychophora: Peripatopsis capensis)
      reveals the impact of Pliocene/Pleistocene climatic oscillations on Afromontane
      forest in the Western Cape, South Africa.
AB  - Habitat specialists such as soft-bodied invertebrates characterized by low
      dispersal capability and sensitivity to dehydration can be employed to examine
      biome histories. In this study, the Cape velvet worm (Peripatopsis capensis) was
      used to examine the impacts of climatic oscillations on historical Afromontane
      forest in the Western Cape, South Africa. Divergence time estimates suggest that
      the P. capensis species complex diverged during the Pliocene epoch. This period
      was characterized by dramatic climatic and topographical change. Subsequently,
      forest expansion and contraction cycles led to diversification within P.
      capensis. Increased levels of genetic differentiation were observed along a west
      to-south-easterly trajectory because the south-eastern parts of the Cape Fold
      Mountain chain harbour larger, more stable fragments of forest patches, have more
      pronounced habitat heterogeneity and have historically received higher levels of
      rainfall. These results suggest the presence of three putative species within P.
      capensis, which are geographically discreet and genetically distinct.

PMID- 22409214
TI  - Pravastatin and simvastatin improves acetylsalicylic acid-mediated in vitro blood
      platelet inhibition.
AB  - BACKGROUND: Insight into the pathophysiology of atherothrombosis indicates that
      an integrated risk factor approach, focusing particularly on the management of
      dyslipidaemia (with statins) and thrombosis (with ASA), may constitute an optimal
      therapeutic approach. We investigated whether pravastatin, simvastatin and
      atorvastatin may directly modulate under in vitro conditions the reactivity of
      blood platelets originating from healthy volunteers. In addition, we analysed the
      influence of statins on the platelet sensitivity to ASA under such conditions.
      MATERIALS AND METHODS: We monitored collagen- or ADP-induced platelet
      aggregation, CD36, PAC-1 and CD62 expression on platelet surface and thromboxane
      generation after incubation with pravastatin, simvastatin, atorvastatin and/or
      ASA. RESULTS: The incubation of whole blood with simvastatin and pravastatin
      significantly decreased CD36 expression. In the presence of 50 MUM ASA,
      simvastatin and pravastatin significantly reduced the PAC-1 expression (30%
      reduction for simvastatin, P < 0.01, and 15% reduction for pravastatin, P <
      0.01), platelet aggregation (20% reduction for both statins, P < 0.01) and
      thromboxane generation (35% reduction for simvastatin, P < 0.001, and 30%
      reduction for pravastatin, P < 0.001) compared to ASA alone. Atorvastatin changed
      neither baseline platelet aggregation nor ASA-mediated platelet inhibition.
      CONCLUSIONS: Our results suggested that statins may directly interact with
      platelet membranes or may modulate a signalling pathway in platelets (the
      pleiotropic effects of statins). It is possible that the statin effect on CD36
      and ASA-mediated protein acetylation can be reached by the modulation of a
      distribution or a function of membrane-associated proteins. Further studies are
      certainly needed to better elucidate the mechanism(s) underlying the statins'
      effects on platelet sensitivity to ASA.

PMID- 22409215
TI  - Genetic and environmental risk factors for submucous cleft palate.
AB  - A multifactorial aetiology with genetic and environmental factors is assumed for
      orofacial clefts. Submucous cleft palate (SMCP), a subgroup of cleft palates with
      insufficient median fusion of the muscles of the soft palate hidden under the
      mucosa, has a prevalence of 1:1,250-1:5,000. We described the prevalence of risk
      factors among 103 German patients with the subtype SMCP and genotyped 24 single
      nucleotide polymorphisms (SNPs) from 12 candidate genes for orofacial clefts.
      Analysis of risk factors yielded a positive history for maternal cigarette
      smoking during pregnancy in 25.2% of the patients, and this was significantly
      more frequent than in the normal population. The group of patients differed in
      allele frequencies at SNP rs3917192 of the gene TGFB3 (nominal P = 0.053) and at
      SNP rs5752638 of the gene MN1 (nominal P = 0.075) compared with 279 control
      individuals. Our results indicate a potential role of maternal smoking during
      pregnancy for the formation of SMCP. The analysis of genetic variants hints at
      the contribution of TGFB3 and MN1 in the aetiology of SMCPs.

PMID- 22409216
TI  - Enamel defects associated with coeliac disease: putative role of antibodies
      against gliadin in pathogenesis.
AB  - Enamel defects in the permanent teeth of patients with coeliac disease (CD) are
      often reported as an atypical manifestation, sometimes being suggestive of an
      undiagnosed atypical disease. We proposed to explore the pathogenesis of these
      oral defects, which are poorly studied. Sequence analyses of proteins from gluten
      (gliadins) and of proline-rich enamel proteins (amelogenin and ameloblastin)
      suggested the presence of common antigenic motifs. Therefore, we analyzed, by
      ELISA and western blotting, the reactivity of sera from patients with CD against
      gliadin and enamel-derived peptides. Correlation analyses between the levels of
      specific antibodies against gliadin and enamel derived peptides and inhibition
      experiments confirmed the presence of cross-reactive antibodies. Immunoblot
      analysis revealed that the most prominent component in enamel matrix derivative
      (of approximately 18.6 kDa), identified by an amelogenin-specific antibody, is
      recognized by sera from patients with CD; in addition, several fractions of pure
      gliadin were recognized by amelogenin-specific antibody. In agreement, sera from
      mice immunized with enamel matrix-derived proteins generated antibodies that
      recognized a peptide (of approximately 21.2 kDa) derived from gliadin. In
      conclusion, antibodies against gliadin generated in patients with CD can react in
      vitro with a major enamel protein. The involvement of anti-gliadin serum in the
      pathogenesis of enamel defects in children with untreated CD can be hypothesized
      on the basis of these novel results.

PMID- 22409217
TI  - Biophysical characterization of synthetic amelogenin C-terminal peptides.
AB  - Amelogenin plays a key role in the formation of the highly mineralized structure
      of tooth enamel. During the secretory stage, amelogenin is cleaved gradually by a
      protease, matrix metalloproteinase-20 (MMP-20), releasing hydrophilic C-terminal
      peptides. In this study, the biophysical properties of synthetic C-terminal
      peptides (of 28, 17, and 11 residues), mimicking native peptides, were explored
      in vitro. A sudden decrease was observed in the zeta (zeta)-potential upon the
      addition of calcium or phosphates, which was also accompanied by an increased
      aggregation propensity of the peptides. Under most of the experimental
      conditions, the particle size increased at a pH 2-3 units higher than the
      isoelectric point (pI) of the peptides, while the peptides existed as smaller
      particles (<2 nm) near their pI values and in the acidic range. They showed poor
      affinity for calcium and phosphates, comparable to full-length amelogenin and
      variants. The secondary structure determination showed that the 11-amino-acid
      peptide contained defined secondary structure comprising beta-sheets and turns.
      Atomic force microscopy analysis revealed the presence of thin, disk-like
      nanostructures of 54.4 nm diameter for the 28-amino-acid peptide and 54.9 nm
      diameter for the 11-amino acid peptide, whereas no definite structures were
      observed for the 17-amino-acid peptide. It is concluded that the amelogenin C
      terminal peptides are capable of interacting with calcium and phosphate ions, of
      self-assembly into nanostructures, and may have some secondary structure, and
      hence may have some role in enamel synthesis.

PMID- 22409218
TI  - Exocyst subunits are involved in isoproterenol-induced amylase release from rat
      parotid acinar cells.
AB  - Exocytosis of secretory granules in parotid acinar cells requires multiple
      events: tethering, docking, priming, and fusion with a luminal plasma membrane.
      The exocyst complex, which is composed of eight subunits (Sec3, Sec5, Sec6, Sec8,
      Sec10, Sec15, Exo70, and Exo84) that are conserved in yeast and mammalian cells,
      is thought to participate in the exocytotic pathway. However, to date, no exocyst
      subunit has been identified in salivary glands. In the present study, we
      investigated the expression and function of exocyst subunits in rat parotid
      acinar cells. The expression of mRNA for all eight exocyst subunits was detected
      in parotid acinar cells by RT-PCR, and Sec6 and Sec8 proteins were localized on
      the luminal plasma membrane. Sec6 interacted with Sec8 after 5 min of stimulation
      with isoproterenol. In addition, antibodies to-Sec6 and Sec8 inhibited
      isoproterenol-induced amylase release from streptolysin O-permeabilized parotid
      acinar cells. These results suggest that an exocyst complex of eight subunits is
      required for amylase release from parotid acinar cells.

PMID- 22409219
TI  - The green tea polyphenol (-)-epigallocatechin gallate precipitates salivary
      proteins including alpha-amylase: biochemical implications for oral health.
AB  - Green tea is a popular drink throughout the world, and it contains various
      components, including the green tea polyphenol (-)-epigallocatechin gallate
      (EGCG). Tea interacts with saliva upon entering the mouth, so the interaction
      between saliva and EGCG interested us, especially with respect to EGCG-protein
      binding. SDS-PAGE revealed that several salivary proteins were precipitated after
      adding EGCG to saliva. Matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry (MALDI-TOF MS) peptide mass fingerprinting indicated that the
      major proteins precipitated by EGCG were alpha-amylase, S100, and cystatins.
      Surface plasmon resonance revealed that EGCG bound to alpha-amylase at
      dissociation constant (K(d)) = 2.74 * 10(-6) M, suggesting that EGCG interacts
      with salivary proteins with a relatively strong affinity. In addition, EGCG
      inhibited the activity of alpha-amylase by non-competitive inhibition, indicating
      that EGCG is effective at inhibiting the formation of fermentable carbohydrates
      involved in caries formation. Interestingly, alpha-amylase reduced the
      antimicrobial activity of EGCG against the periodontal bacterium Aggregatibacter
      actinomycetemcomitans. Therefore, we considered that EGCG-salivary protein
      interactions might have both protective and detrimental effects with respect to
      oral health.

PMID- 22409220
TI  - Effect of various pH values, ionic strength, and temperature on papain hydrolysis
      of salivary film.
AB  - Stimulated human whole saliva (WS) was used to study the dynamics of papain
      hydrolysis at defined pH, ionic strength, and temperature with the view of
      reducing an acquired pellicle. A quartz crystal microbalance with dissipation
      (QCM-D) was used to monitor the changes in frequency caused by enzyme hydrolysis
      of WS films, and the hydrolytic parameters were calculated using an empirical
      model. The morphological and conformational changes of the salivary films before
      and after enzymatic hydrolysis were characterized by atomic force microscopy
      (AFM) imaging and grazing-angle Fourier transform infrared (GA-FTIR ) spectra,
      respectively. The characteristics of papain hydrolysis of WS films were pH-,
      ionic strength-, and temperature-dependent. The WS films were partially removed
      by the action of papain, resulting in thinner and smoother surfaces. The infrared
      data suggested that hydrolysis-induced deformation did not occur on the remnants
      of salivary films. The processes of papain hydrolysis of WS films can be
      controlled by properly regulating pH, ionic strength, and temperature.

PMID- 22409222
TI  - Effects of time and socio-economic status on the determinants of oral health
      related behaviours of parents of preschool children.
AB  - The oral health-related beliefs of parents have an important impact on the oral
      health status of their children; however, they are not stable over time. This
      study aimed to assess the changes, over time, in the determinants of parental
      oral health-related behaviour based on the Theory of Planned Behaviour and to
      investigate socio-economic inequalities. The cohort consisted of the parents -
      mainly the mothers - of 1,057 children born in 2003 and 2004 in Flanders
      (Belgium). According to the Theory of Planned Behaviour, validated
      questionnaires, completed at children's birth and at age 3 and 5 yr, assessed
      parental attitudes, social norms, perceived behavioural control, and intention
      towards three behaviours: dietary habits, oral hygiene habits, and dental
      attendance. Linear mixed-model analyses were applied. Positive parental attitudes
      towards oral health-related behaviours increased between birth and 3 yr of age,
      whereas the scores for subjective norms and intentions decreased. Scores remained
      stable for children between three and 5 yr of age. Highly educated mothers had
      significantly higher scores for attitudes, perceived behavioural control, and
      intentions than less-educated mothers. Health promotion campaigns should take
      these natural changes and inequalities of dental beliefs into account when
      developing and evaluating interventions.

PMID- 22409221
TI  - Root resorption of primary molars without successor teeth. An experimental study
      in the beagle dog.
AB  - Tooth agenesis is a common craniofacial congenital malformation in humans, but
      little is known about the mechanisms of root resorption in this condition. The
      purpose of this study was to investigate the mechanisms of root resorption in
      primary molars without successors. An animal model without permanent tooth germs
      was established by surgery in beagles. The times of onset of primary molar root
      resorption, with and without successors, were compared. The distribution of
      immune cells, odontoclasts, and their activating factors were determined by
      histochemistry and immunohistochemistry. Root resorption of primary mandibular
      molars without successors began later than physiological resorption. In primary
      molars without permanent germs, odontoclasts and immune cells were present mainly
      in the apical pulp at the start of root resorption, whereas in control teeth
      receptor activator of nuclear factor-kappaB ligand (RANKL)-positive cells were
      found mainly in the region of the periodontal ligament. CD14(+) and CD3(+) cells
      were found in both the pulp and the periodontal ligament region. These results
      suggest that the dental pulp of primary molars, as well as immune cells, may play
      an important role in root resorption in primary molars without permanent tooth
      germs.

PMID- 22409223
TI  - Influence of cavity design on the biomechanics of direct composite resin
      restorations in Class IV preparations.
AB  - This study evaluated the effect of cavity design on stress distribution and
      fracture resistance of direct composite resin restorations in Class IV
      preparations. A finite element analysis (FEA) model of the maxillary central
      incisor with a Class IV cavity was established. Five model variations were
      studied: (i) a 1-mm bevel (ii) a 2-mm bevel, (iii) a plain chamfer, (iv) a stair
      step chamfer, and (v) butt joints (a control configuration). All FEA variations
      modeled a tooth restored with composite resin loaded under 100 N at an angle of
      45 degrees  to the longitudinal axis. The interfacial von Mises stress was
      evaluated. The FEA was complemented with an in vitro assessment. Fracture
      resistance of direct composite resin restorations was tested with a universal
      testing machine and fracture patterns were observed. Finite element analysis
      showed that stress in chamfer and stair-step chamfer models was more homogenously
      distributed, while stress in bevel models was relatively concentrated at lingual
      regions. Fracture resistance of a 1-mm bevel preparation was lower than for the 2
      mm bevel, plain chamfer, and stair-step chamfer preparations, but was higher than
      for butt joints. The stair-step chamfer group presented the most favorable
      failure pattern. Considering biomechanics and esthetics, the present study
      indicates that the stair-step chamfer and 2-mm bevel should be recommended for
      clinical restoration.

PMID- 22409224
TI  - Influence of air-abrasion executed with polyacrylic acid-Bioglass 45S5 on the
      bonding performance of a resin-modified glass ionomer cement.
AB  - The aim of this study was to test the microtensile bond strength (MUTBS), after 6
      months of storage in PBS, of a resin-modified glass ionomer cement (RMGIC) bonded
      to dentine pretreated with Bioglass 45S5 (BAG) using various etching and air
      abrasion techniques. The RMGIC (GC Fuji II LC) was applied onto differently
      treated dentine surfaces followed by light curing for 30 s. The specimens were
      cut into matchsticks with cross-sectional areas of 0.9 mm(2). The MUTBS of the
      specimens was measured after 24 h or 6 months of storage in PBS and the results
      were statistically analysed using two-way anova and the Student-Newman-Keuls test
      (alpha = 0.05). Further RMCGIC-bonded dentine specimens were used for interfacial
      characterization, micropermeability, and nanoleakage analyses by confocal
      microscopy. The RMGIC-dentine interface layer showed no water absorption after 6
      months of storage in PBS except for the interdiffusion layer of the silicon
      carbide (SiC)-abraded/polyacrylic acid (PAA)-etched bonded dentine. The RMGIC
      applied onto dentine air-abraded with BAG/H(2)O only or with BAG/PAA-fluid
      followed by etching procedures (10% PAA gel) showed no statistically significant
      reduction in MUTBS after 6 months of storage in PBS. The abrasion procedures
      performed using BAG in combination with PAA might be a suitable strategy to
      enhance the bonding durability and the healing ability of RMGIC bonded to
      dentine.

PMID- 22409225
TI  - Effect of alpha-thalassaemia on exercise-induced oxidative stress in sickle cell
      trait.
AB  - AIM: Alpha-thalassaemia is known to reduce intra-erythrocyte HbS (sickle
      haemoglobin) concentration in sickle cell trait (SCT) subjects. Because HbS was
      shown to increase oxidative stress, the purpose of this study was to assess the
      effects of the coexistence of alpha-thalassaemia and SCT on oxidative stress
      markers and nitric oxide (NO) metabolism after an acute physical exercise.
      METHODS: Forty subjects (age: 23.5 +/- 2.21 years), SCT carriers (HbAS) or
      healthy subjects (HbAA), with (-alphaT) or without (-NalphaT) an associated alpha
      thalassaemia took part in the study. Plasma markers of oxidative stress [advanced
      oxidation protein products (AOPP), protein carbonyl, malondialdehyde (MDA) and
      nitrotyrosine], anti-oxidant defences and NO metabolism (NOx) were measured at
      rest (T(rest)), immediately following an incremental maximal exercise test
      (T(ex)) and during recovery (T(1h), T(2h) and T(24h)). RESULTS: Malondialdehyde
      expressed as the percentage of changes from baseline was significantly higher in
      the HbAS-NalphaT compared with HbAS-alphaT during recovery (+36.3 +/- 14.1% vs. 
      1.8 +/- 13.2% at T(1h), P = 0.02; +36.6 +/- 13.4% vs. -11.4 +/- 12.5% at T(2h), P
      = 0.004 and +24.1 +/- 12.3% vs. -14.4 +/- 11.5% at T(24h), P = 0.02 in HbAS
      NalphaT vs. HbAS-alphaT). Compared with HbAS-NalphaT, HbAS-alphaT had a higher
      NOx change from baseline at T(ex) (-23.4 +/- 20.6% vs. +57.7 +/- 19.3%,
      respectively; P = 0.005) and lower nitrotyrosine change from baseline at T(1h)
      (+7.2 +/- 22.2% vs. +93.5%+/-29.3%, respectively; P = 0.04). CONCLUSION: All
      these data suggest that the presence of alpha-thalassaemia may blunt the higher
      level of oxidative stress and the impaired bioavailability of NO observed in the
      SCT carriers.

PMID- 22409226
TI  - Signet-ring cell differentiation in FNA cytology of a primitive thyroid
      carcinoma.

PMID- 22409227
TI  - Indignity, exclusion, pain and hunger: the impact of musculoskeletal impairments
      in the lives of children in Malawi.
AB  - PURPOSE: To develop a conceptual model representing the impact of musculoskeletal
      impairments (MSIs) in the lives of children in Malawi. METHOD: A total of 169
      children with MSIs (CMSIs), family and other community members participated in 57
      interviews, focus groups and observations. An inductive approach to data analysis
      was used to conceptualise the impact of MSIs in children's day-to-day lives.
      RESULTS: The main themes that emerged were Indignity, Exclusion, Pain and Hunger.
      Indignity represents various affronts to children's sense of inherent equal worth
      as human beings, for example when bullied by peers. Exclusion refers to CMSIs
      being excluded from three core daily activities: school, play and household
      chores. Some CMSIs experienced Pain, for example as an outcome of striving to
      participate. Children with severe mobility impairments were at increased risk of
      Hunger, having less access to food outside the home and placing a burden of care
      on the family that could restrict household productivity. Household Poverty was
      therefore included in the model, as this household impact was inseparable from
      the impact on CMSIs. CONCLUSION: It is recommended that rehabilitation
      interventions are planned and evaluated with consideration to their impact on
      Exclusion, Indignity, Pain, Hunger and Household Poverty using multi-faceted
      partnerships.

PMID- 22409228
TI  - A paradigm for enzyme-catalyzed proton transfer at carbon: triosephosphate
      isomerase.
AB  - Triosephosphate isomerase (TIM) catalyzes the stereospecific 1,2-proton shift at
      dihydroxyacetone phosphate (DHAP) to give (R)-glyceraldehyde 3-phosphate through
      a pair of isomeric enzyme-bound cis-enediolate phosphate intermediates. The
      chemical transformations that occur at the active site of TIM were well
      understood by the early 1990s. The mechanism for enzyme-catalyzed isomerization
      is similar to that for the nonenzymatic reaction in water, but the origin of the
      catalytic rate acceleration is not understood. We review the results of
      experimental work that show that a substantial fraction of the large 12 kcal/mol
      intrinsic binding energy of the nonreacting phosphodianion fragment of TIM is
      utilized to activate the active site side chains for catalysis of proton
      transfer. Evidence is presented that this activation is due to a phosphodianion
      driven conformational change, the most dramatic feature of which is closure of
      loop 6 over the dianion. The kinetic data are interpreted within the framework of
      a model in which activation is due to the stabilization by the phosphodianion of
      a rare, desolvated, loop-closed form of TIM. The dianion binding energy is
      proposed to drive the otherwise thermodynamically unfavorable desolvation of the
      solvent-exposed active site. This reduces the effective local dielectric constant
      of the active site, to enhance stabilizing electrostatic interactions between
      polar groups and the anionic transition state, and increases the basicity of the
      carboxylate side chain of Glu-165 that functions to deprotonate the bound carbon
      acid substrate. A rebuttal is presented to the recent proposal [Samanta, M.,
      Murthy, M. R. N., Balaram, H., and Balaram, P. (2011) ChemBioChem 12, 1886-1895]
      that the cationic side chain of K12 functions as an active site electrophile to
      protonate the carbonyl oxygen of DHAP.

PMID- 22409229
TI  - Diffusion of 1,2-dimethoxyethane and 1,2-dimethoxypropane through
      phosphatidycholine bilayers: a molecular dynamics study.
AB  - In this paper, a theoretical study of 1,2-dimethoxyethane (DME) and 1,2
      dimethoxypropane (DMP) at water/n-heptane and 1,2-dimyristoyl-sn-glycero-3
      phospatidycholine (DMPC) lipid bilayer/water interfaces using the umbrella
      sampling method is reported. Recently proposed GROMOS96/OPLS compatible models
      for DME and DMP have been used for the simulation studies. The percolation free
      energy barrier of one DME and DMP molecule from water to n-heptane phase
      calculated using the umbrella sampling method turned out to be equal to ~18.5
      kJ/mol and ~6 kJ/mol, respectively. In the case of the DMPC lipid bilayer,
      overall free energy barriers of ~20 kJ/mol and ~12 kJ/mol were obtained for DME
      and DMP, respectively. The spontaneous diffusion of DME and DMP in the lipid
      bilayer has also been investigated using unconstrained molecular dynamics
      simulations at the water/DMPC interface and inside the lipid bilayer. As expected
      from the estimated percolation barriers, simulation results show that DME,
      contrary to DMP, spontaneously diffuse into the aqueous solution from the lipid
      interior. In addition, simulations with multiple DME or DMP molecules at the
      interface show spontaneous diffusion within 50 ns inside the DMPC layer only for
      DMP.

PMID- 22409230
TI  - The effect of study type on body weight and tumor incidence in B6C3F1 mice fed
      the NTP-2000 diet.
AB  - The B6C3F1 mouse is the standard mouse strain used in National Toxicology Program
      (NTP) carcinogenesis studies. Over time, increased liver tumorigenesis that was
      correlated with elevated body weights was noted in males and females. NTP
      therefore replaced the NIH-07 diet with the NTP-2000 diet and returned to group
      housing of females as lower body weights were noted in group housed mice.
      However, recent studies reported study-type differences in body weights at 3
      months using the NTP-2000 diet with higher weights evident in drinking water and
      inhalation studies compared to feed studies. Therefore, body weight and tumor
      incidence data were collected for untreated control mice from all 2-year NTP feed
      (12), drinking water (8), water gavage (6) and inhalation (10) studies that used
      the NTP-2000 diet in order to assess the impact of study type on body weights and
      tumor incidences. Results show statistically significant elevated body weights
      and liver tumor incidences in males and females from drinking water, water gavage
      and inhalation studies compared to results from feed studies. Thus, the elevated
      body weights and liver tumorigenesis noted in mice using the NIH-07 diet were
      also evident using the NTP-2000 diet, which was introduced to address body weight
      elevations. Given the study-type dependent effects noted, these results emphasize
      the importance of carefully selecting historical control data for B6C3F1 mice.
      Moreover, because of the association between body weight and liver tumorigenesis,
      these results may have implications regarding dose-level selection for
      carcinogenicity studies involving B6C3F1 mice based on the maximum tolerated
      dose.

PMID- 22409231
TI  - Cost-effectiveness of denosumab vs zoledronic acid for prevention of skeletal
      related events in patients with solid tumors and bone metastases in the United
      States.
AB  - OBJECTIVE: With increasing healthcare resource constraints, it has become
      important to understand the incremental cost-effectiveness of new medicines.
      Subcutaneous denosumab is superior to intravenous zoledronic acid (ZA) for the
      prevention of skeletal-related events (SREs) in patients with advanced solid
      tumors and bone metastases. This study sought to determine the lifetime cost
      effectiveness of denosumab vs ZA in this setting, from a US managed-care
      perspective. METHODS: A lifetime Markov model was developed, with relative rate
      reductions in SREs for denosumab vs ZA derived from three pivotal Phase 3 trials
      involving patients with castration-resistant prostate cancer (CRPC), breast
      cancer, and non-small-cell lung cancer (NSCLC), and bone metastases. The real
      world SRE rates in ZA-treated patients were derived from a large commercial
      database. SRE and treatment administration quality-adjusted life year (QALY)
      decrements were estimated with time-trade-off studies. SRE costs were estimated
      from a nationally representative commercial claims database. Drug, drug
      administration, and renal monitoring costs were included. Costs and QALYs were
      discounted at 3% annually. One-way and probabilistic sensitivity analyses were
      conducted. RESULTS: Across tumor types, denosumab was associated with a reduced
      number of SREs, increased QALYs, and increased lifetime total costs vs ZA. The
      costs per QALY gained for denosumab vs ZA in CRPC, breast cancer, and NSCLC were
      $49,405, $78,915, and $67,931, respectively, commonly considered good value in
      the US. Costs per SRE avoided were $8567, $13,557, and $10,513, respectively.
      Results were sensitive to drug costs and SRE rates. LIMITATIONS: Differences in
      pain severity and analgesic use favoring denosumab over ZA were not captured.
      Mortality was extrapolated from fitted generalized gamma function beyond the
      trial duration. CONCLUSION: Denosumab is a cost-effective treatment option for
      the prevention of SREs in patients with advanced solid tumors and bone metastases
      compared to ZA. The overall value of denosumab is based on superior efficacy,
      favorable safety, and more efficient administration.

PMID- 22409232
TI  - Health services research in heart failure patients treated with a remote
      monitoring device in Germany-a retrospective database analysis in evaluating
      resource use.
AB  - OBJECTIVES: Heart failure is an increasing burden for all healthcare systems with
      prevalence reaching over 20 million patients worldwide and direct costs of
      disease requiring ~1% of healthcare budget expenditures. Beyond traditional
      pharmaceutical treatment, medical devices and remote monitoring tools were
      introduced to ensure a closely managed control of patients. In this context, a
      decision-maker needs to know whether the new technology provides clinical benefit
      towards patients and what resource use is attached to them. METHODS: Health
      services research is a complementary approach to clinical trials providing
      results to the impact of the technology in real life settings. As an example this
      study reports of a secondary data analysis of one of the largest health insurance
      companies in Germany, comparing resource use of heart failure patients receiving
      a cardiac resynchronization therapy (CRT) device coupled with a fluid status
      monitoring and alert function with patients receiving conventional CRT, ICD
      (implantable cardioverter defibrillator), or no intervention. RESULTS: Disease
      associated expenses can be attributed to far more than 50% to heart failure.
      Although implementation of the CRT device with alert function was most expensive
      (31,794 Euros compared to 27,659 Euros in the conventional CRT group, 24,128
      Euros in the ICD group, and 3735 Euros in the no intervention group) in the first
      year after implementation, the least costs have been caused in this group (7000
      Euros compared to more than 11,000 Euros in all other groups). CONCLUSION: This
      article highlights potential health services research approaches focusing on the
      example of a CRT device coupled with a pulmonary diagnostic and alert function.
      Although this retrospective analysis holds a number of limitations (e.g., small
      number of patients in intervention group, cost calculations only from the payer
      perspective), and despite the need for randomized controlled trials, it was shown
      that secondary data research in this field is a valuable approach.

PMID- 22409233
TI  - Development of a microsatellite-based method for the differentiation of European
      wild boar (Sus scrofa scrofa) from domestic pig breeds (Sus scrofa domestica) in
      food.
AB  - Twenty microsatellites (simple sequence repeats, SSR) were used to discriminate
      wild boar from domestic pig and to identify mixtures of the two. Reference groups
      of wild boar and pig samples were collected from the UK and Europe for genetic
      assignment tests. Bayesian Analysis of Populations software (BAPs) gave 100%
      correct assignment for blind wild boar and pig samples and correctly identified
      mixed samples. DNA was extracted from 12 commercial food samples (11 labeled as
      containing wild boar) including pates, salamis, and sausage, and good SSR
      profiles were obtained. Eleven samples were correctly assigned as pig, and two as
      mixed meats. One sample sold as wild boar meat was clearly assigned as pig. A
      further 10 blind samples of meat cuts were analyzed, eight wild boar and two pig,
      and all were correctly assigned.

PMID- 22409234
TI  - The regulatory network menin-microRNA 26a as a possible target for RNA-based
      therapy of bone diseases.
AB  - MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression,
      interplaying with transcription factors in complex regulatory networks. Menin is
      the product of the MEN1 oncosuppressor gene, responsible for multiple endocrine
      neoplasia type 1 syndrome. Recent data suggest that menin functions as a general
      regulator of transcription. Menin expression modulates mesenchymal cell
      commitment to the myogenic or osteogenic lineages. The microRNA 26a (miR-26a)
      modulates the expression of SMAD1 protein during the osteoblastic differentiation
      of human adipose tissue-derived stem cells (hADSCs). We used siRNA silencing
      against MEN1 mRNA and pre-miR-26 mimics to study the interplay between them and
      to investigate the interplay between menin and miR-26a as regulators of
      osteogenic differentiation in the hADSCs. We found that in hADSCs the siRNA
      induced silencing of MEN1 mRNA resulted in a down regulation of miR-26a, with a
      consequent up-regulation of SMAD1 protein. Chromatin immunoprecipitation (ChIP)
      showed that menin occupies the miR-26-a gene promoter, thus inducing its
      expression and confirming that menin is a positive regulator of miR-26a. In
      conclusion, results from this study evidenced, for the first time, a direct
      interaction between menin transcription factor and miRNA, interaction that seems
      to play a pivotal role during the hADSCs osteogenesis, thus suggesting a novel
      target for bone disease RNA-based therapy.

PMID- 22409235
TI  - Peptide-based in vivo delivery agents for oligonucleotides and siRNA.

PMID- 22409236
TI  - 3D coupling of fibronectin fibril arrangement with topology of ventral plasma
      membrane.
AB  - Interaction of integrins with extracellular matrices is essential for cell
      adhesion to substrata. Ventral surfaces of fibroblasts adhering to flat substrata
      are not flat but have uneven 3D topology. However, spatial relationship between
      the topology of the ventral cell surface and arrangement of extracellular matrix
      fibrils remains unclear. Here, we report a novel and simple method based on total
      internal reflection fluorescence microscopy to quantify the distance between the
      ventral plasma membrane and the glass substratum. We observe that the distance
      varies from < 25 nm at focal adhesions to 40-50 nm at close contacts and > 80 nm
      in other regions. Furthermore, by applying this novel method, we show that
      fibronectin fibrils are also separated from the substratum in regions where the
      ventral cell surface-substratum distance is > 80 nm. Our results reveal that
      fibronectin fibrils are not simply adsorbed to the glass substratum but follow
      the ventral cell surface topology.

PMID- 22409237
TI  - Infrared laser ablation sample transfer for MALDI imaging.
AB  - An infrared laser was used to ablate material from tissue sections under ambient
      conditions for direct collection on a matrix assisted laser desorption ionization
      (MALDI) target. A 10 MUm thick tissue sample was placed on a microscope slide and
      was mounted tissue-side down between 70 and 450 MUm from a second microscope
      slide. The two slides were mounted on a translation stage, and the tissue was
      scanned in two dimensions under a focused mid-infrared (IR) laser beam to
      transfer material to the target slide via ablation. After the material was
      transferred to the target slide, it was analyzed using MALDI imaging using a
      tandem time-of-flight mass spectrometer. Images were obtained from peptide
      standards for initial optimization of the system and from mouse brain tissue
      sections using deposition either onto a matrix precoated target or with matrix
      addition after sample transfer and compared with those from standard MALDI mass
      spectrometry imaging. The spatial resolution of the transferred material is
      approximately 400 MUm. Laser ablation sample transfer provides several new
      capabilities not possible with conventional MALDI imaging including (1) ambient
      sampling for MALDI imaging, (2) area to spot concentration of ablated material,
      (3) collection of material for multiple imaging analyses, and (4) direct
      collection onto nanostructure assisted laser desorption ionization (NALDI)
      targets without blotting or ultrathin sections.

PMID- 22409238
TI  - Plasma factor VII-activating protease antigen levels and activity are increased
      in ischemic stroke.
AB  - BACKGROUND: Factor VII-activating protease (FSAP) is a recently discovered plasma
      protease with a role in the regulation of hemostasis and vascular remodeling
      processes. Higher levels and activity of FSAP have been reported in patients with
      deep vein thrombosis, but there are no data on plasma FSAP in ischemic stroke
      (IS). OBJECTIVE: To investigate whether FSAP antigen levels and activity are
      associated with IS and/or etiologic subtypes of IS. PATIENTS AND METHODS: To
      assess the potential association between FSAP and IS, plasma FSAP antigen levels
      and activity were measured in 600 consecutive IS patients and 600 population
      based controls from the case-control study the Sahlgrenska Academy Study on
      Ischemic Stroke (SAHLSIS). Blood sampling was performed in the acute phase and 3
      months after the index stroke. FSAP was also investigated at the genetic level by
      genotyping of 33 single-nucleotide polymorphisms. RESULTS: Increased FSAP antigen
      level and activity, at both time-points, were independently associated with IS.
      Subtype analysis revealed similar associations for both FSAP measures, at both
      time-points, in all main IS subtypes. FSAP genotypes showed association with both
      FSAP plasma measurements, but not with IS. CONCLUSIONS: Increased plasma FSAP
      antigen levels and activity were associated with IS and all main etiologic
      subtypes, suggesting a possible role for FSAP in the pathophysiology of IS,
      irrespective of the underlying etiology.

PMID- 22409239
TI  - Modifying the fullerene surface using endohedral noble gas atoms: density
      functional theory based molecular dynamics study of C70O3.
AB  - We have performed a series of ab initio molecular orbital and molecular dynamics
      calculations to ascertain the influence of an endohedral noble gas atom on the
      reactivity of the surface of the model system C(70)O(3). Our simulations show
      that the minimum energy pathways for the ozone ring-opening reaction are
      influenced by the presence of the endohedral atom. The effect is isomer
      dependent, with the enthalpy of the reaction increasing for a,b-C(70)O(3) and
      decreasing for e,e-C(70)O(3) when doped with the heavy noble gas atoms Xe and Rn.

PMID- 22409240
TI  - Clinical risk management in hospitals: strategy, central coordination and
      dialogue as key enablers.
AB  - OBJECTIVE: The study aims to identify key enablers fostering clinical risk
      management (CRM) in hospitals to guide health care in this vital area of patient
      safety. METHOD: A cross-sectional survey was conducted at the national level in
      324 Swiss hospitals in 2007-2008 to assess the relationship between key elements
      and systematic CRM. Therefore, a comprehensive monitoring instrument for CRM was
      used for the first time. Organizational factors (e.g. strategy, coordination,
      resources) and structural conditions (e.g. hospital size) were tested as key
      elements. CRM was assessed by evaluating its maturity (i.e. the level of CRM
      development) by 12 theoretically derived indices joining together essential
      aspects of CRM at the hospital level and the service level. Chi-square measures
      were used to analyse the relationships between organizational factors or
      structural conditions and maturity of CRM. RESULTS: Participation in this
      voluntary survey was good, with CRM experts of 138 out of 324 hospitals
      responding (response rate 43%). Three key enablers for CRM were identified:
      implementing a function for central CRM coordination, assuring dialogue with and
      between the different hospital services, and developing strategic CRM objectives.
      CONCLUSIONS: This study offers, for the first time, an assessment of the maturity
      of hospitals' CRM and identifies key enablers related to CRM. This is a feasible
      first step in guiding hospitals to shape their CRM and presents a basis for
      future studies, for example, linking CRM to outcome data.

PMID- 22409241
TI  - The high-throughput yeast deletion fitness data and the theories of dominance.
AB  - The development of high-throughput fitness measurement methods provides
      unprecedented power to test evolutionary theories. However, with this comes new
      challenges regarding data quality and data analysis. We illustrate this by
      reanalysing the fitness distribution in several environments of yeast mutants
      (homo- and heterozygous) from the yeast deletion project. Originally created to
      study functional properties of genes, evolutionary biologists took advantage of
      this database to study evolutionary questions, such as dominance for fitness of
      mutations. We uncover several problems in this data set strongly affecting these
      questions that have remained unnoticed despite the numerous studies based on it.
      High-throughput methodologies are necessarily challenging, both experimentally
      and for data analysis: our point is not to criticize these approaches, but to
      pinpoint these challenges and to propose several improvements that may help avoid
      several shortcomings. Further, in the light of this finding, we question the
      conclusions regarding theories of dominance that have been made using this data
      set. We show that the data on deletion of small effects are not sufficiently
      reliable to be informative on this question. On the other hand, deletions of
      large effect exhibit no correlation between homo- and heterozygous fitness
      effects, a pattern that sheds new light on the h-s correlation issue, with
      several consequences for the debate over the different theories of dominance.

PMID- 22409242
TI  - Common skin conditions in children with HIV/AIDS.
AB  - The most recent Joint United Nations Programme on HIV/AIDS (UNAIDS) data inform
      us that approximately 2.3 million children were infected with HIV at the end of
      2009. The greatest burden of this infection is thrust squarely on the most
      impoverished healthcare systems in the world. Sub-Saharan Africa is home to at
      least 68% of the global total of HIV infection of 22.5 million. Although a scale
      up of antiretrovirals has been one of the UNAIDS priorities, and access to
      services to prevent mother-to-child transmission has increased, an estimated
      370,000 children were newly infected in 2009. Hence, infected mothers continue
      giving birth to HIV-infected children who require appropriate healthcare to
      diagnose and treat their underlying immunodeficiency and related disorders. Skin
      lesions are common in these children as they present with infections common in
      the general population, albeit more severe. Those lesions that are markers of HIV
      or AIDS are important signs heralding an improving or declining immune system and
      the success of antiretrovirals. Cutaneous manifestations of HIV/AIDS can be
      classified broadly as infections and infestations, inflammatory conditions,
      tumors, and antiretroviral related. This manuscript discusses the more common
      skin conditions seen in children infected with HIV so as to improve the diagnosis
      and therapy administered by healthcare professionals especially in sub-Saharan
      Africa.

PMID- 22409243
TI  - Grid refinement in Cartesian coordinates for groundwater flow models using the
      divergence theorem and Taylor's series.
AB  - Grid refinement is introduced in a numerical groundwater model to increase the
      accuracy of the solution over local areas without compromising the run time of
      the model. Numerical methods developed for grid refinement suffered certain
      drawbacks, for example, deficiencies in the implemented interpolation technique;
      the non-reciprocity in head calculations or flow calculations; lack of accuracy
      resulting from high truncation errors, and numerical problems resulting from the
      construction of elongated meshes. A refinement scheme based on the divergence
      theorem and Taylor's expansions is presented in this article. This scheme is
      based on the work of De Marsily (1986) but includes more terms of the Taylor's
      series to improve the numerical solution. In this scheme, flow reciprocity is
      maintained and high order of refinement was achievable. The new numerical method
      is applied to simulate groundwater flows in homogeneous and heterogeneous
      confined aquifers. It produced results with acceptable degrees of accuracy. This
      method shows the potential for its application to solving groundwater heads over
      nested meshes with irregular shapes.

PMID- 22409244
TI  - Formation of layered Fe(II)-Al(III)-hydroxides during reaction of Fe(II) with
      aluminum oxide.
AB  - The reactivity of aqueous Fe(II) with aluminum oxide in anoxic solutions was
      investigated with batch kinetic experiments combined with Fe K edge X-ray
      absorption spectroscopy measurements to characterize Fe(II) sorption products.
      Formation of Fe(II)-Al(III)-layered double hydroxides with an octahedral sheet
      structure similar to nikischerite (NaFe(II)(6) Al(3)(SO(4))(2)(OH)(18)
      (H(2)O)(12)) was observed within a few hours during sorption at pH 7.5 and
      aqueous Fe(II) concentrations of 1-3 mM. These Fe(II) phases are composed of
      brucite-like Fe(II)(OH)(2) sheets with partial substitution of Al(III) for
      Fe(II), charge balanced by anions coordinated along the basal planes. Their fast
      rate of formation suggests that these previously unrecognized Fe(II) phases,
      which are structurally and compositionally similar to green rust, may be an
      important sink of Fe(II) in suboxic and anoxic geochemical environments, and
      impact the fate of structurally compatible trace metals, such as Co(II), Ni(II),
      and Zn(II), as well as redox-reactive species including Cr(VI) and U(VI). Further
      studies are required to assess the thermodynamics, formation kinetics, and
      stability of these Fe(II) minerals under field conditions.

PMID- 22409245
TI  - Use of an interactive video gaming program compared with conventional
      physiotherapy for hospitalised older adults: a feasibility trial.
AB  - PURPOSE: To assess the feasibility of a physiotherapy intervention using an
      interactive gaming program compared with conventional physiotherapy for
      hospitalised older people. METHODS: Randomised controlled pilot study in a
      geriatric rehabilitation unit within an acute public hospital. Participants were
      randomly allocated to physiotherapy using an interactive gaming program (n = 22)
      or conventional physiotherapy in a ward-based gym (n = 22). Feasibility was
      assessed by comparing the effects of the intervention on clinical outcome
      measures (primary outcome: mobility as assessed by the Timed Up and Go test,
      secondary outcomes: safety, adherence levels, eligibility and consent rates).
      RESULTS: Participants (n = 44) had a mean age of 85 years (SD 4.5) and the
      majority (80%) were women. Univariable analyses showed no significant difference
      between groups following intervention. However, multivariable analyses suggested
      that participants using the interactive gaming program improved more on the Timed
      Up and Go test (p = 0.048) than participants receiving conventional
      physiotherapy. There were no serious adverse events and high levels of adherence
      to therapy were evident in both groups. Only a small proportion of patients
      screened were recruited to the study. CONCLUSIONS: In this feasibility study, the
      use of a commercially available interactive gaming program by physiotherapists
      with older people in a hospital setting was safe and adherence levels were
      comparable with conventional therapy. Preliminary results suggest that further
      exploration of approaches using games as therapy for older people could include
      commonly used measures of balance and function.

PMID- 22409246
TI  - Psychometric evaluation of the HIV symptom distress scale.
AB  - The objective of this article is to psychometrically validate the HIV symptom
      distress scale (SDS), an instrument that can be used to measure overall HIV
      symptom distress or clinically relevant groups of HIV symptoms. A secondary data
      analysis was conducted using the Collaborations in HIV Outcomes Research US
      Cohort (CHORUS). Inclusion criteria required study participants (N=5521) to have
      a valid baseline measure of the AIDS Clinical Trial Group Symptom Distress
      Module, with an SF-12 or SF-36 completed on the same day. Psychometric testing
      assessed unidimensionality, internal consistency, and factor structure using
      exploratory and confirmatory factor analysis, and structural equation modeling
      (SEM). Construct validity examined whether the new measure discriminates across
      clinical significance (CD4 and HIV viral load). Findings show that the SDS has
      high reliability (alpha=0.92), and SEM supports a correlated second-order factor
      model (physical and mental distress) with acceptable fit (GFI=0.88, AGFI=0.85,
      NFI=0.99, NNFI=0.99; RMSEA=0.06, [90% CI 0.06 - 0.06]; Satorra Bentler scaled, C
      (2) =3274.20; p=0.0). Construct validity shows significant differences across
      categories for HIV-1 viral load (p<0.001) and CD4 (p<0.001). Differences in mean
      SDS scores exist across gender (p<0.001), race/ethnicity (p<0.05), and
      educational attainment (p<0.001). Hence, the HIV SDS is a reliable and valid
      instrument, which measures overall HIV symptoms or clinically relevant groups of
      symptoms.

PMID- 22409247
TI  - A mass lesion in the skull after radiotherapy for medulloblastoma.

PMID- 22409248
TI  - p38 mitogen-activated protein kinase is not activated in the quadriceps of
      patients with stable chronic obstructive pulmonary disease.
AB  - Quadriceps weakness is associated with a poor prognosis in COPD. Several data
      suggest that immobility and muscle wasting may be related through up-regulation
      of the p38 Mitogen associated protein kinase (MAPK) signalling pathway. We
      therefore hypothesised that this might occur in the quadriceps of COPD patients.
      We studied 105 stable COPD outpatients (mean FEV(1) 43.9% predicted) and 27 age
      and gender matched controls. We measured fat-free mass, quadriceps strength and
      daily physical activity using triaxial accelerometry. A quadriceps biopsy was
      obtained in which components of the p38-MAPK signalling pathway were examined.
      Patients had reduced fat-free mass index (16.1 (2.2) kg/m(2) vs 17.2 (2.2)
      kg/m(2), p = 0.02) and exhibited quadriceps weakness (mean (SD) maximal voluntary
      contraction force 72.1% (18.7) predicted and 82.3% (7.1) predicted for patients
      and controls respectively, p = 0.01). Physical activity was significantly reduced
      in the patient group; in particular mean (SD) locomotion time was 101 (48)
      minutes/12 hours in controls and 48 (31) minutes in patients (p < 0.0001).
      However, in biopsies obtained from these patients, no differences were observed
      for total or phosphorylated HSP27 or p38 MAPK protein or p38 MAPK mRNA (MAPK14);
      of the downstream products both GADD45beta and c-jun mRNA were reduced in COPD
      patients while c-myc was not different from controls. No parameter correlated
      with physiological data within the patient group. We conclude that, despite the
      presence of reduced fat-free mass, quadriceps weakness and inactivity, p38 MAPK
      signalling was not up-regulated in skeletal muscle of stable out-patients with
      COPD.

PMID- 22409249
TI  - Receptor binding by influenza virus: using computational techniques to extend
      structural data.
AB  - Influenza attaches to host cells via hemagglutinin binding of cell-surface
      glycans. These relatively low-affinity interactions involving flexible ligands
      are critical in determining tissue and host specificity, but their dynamic nature
      complicates structural characterization of hemagglutinin-receptor complexes.
      Molecular simulation can assist in analyzing glycan and protein flexibility in
      crystallized complexes, assessing how binding might change under mutation or
      altered glycosylation patterns, and evaluating how soluble ligands may relate to
      physiological presentation on the plasma membrane. Molecular dynamics simulation
      also has the potential to help integrate structural and dynamic data sources.
      Here we review recent progress from analysis of molecular dynamics simulation and
      outline challenges for the future.

PMID- 22409250
TI  - Eculizumab in the treatment of refractory idiopathic thrombotic thrombocytopenic
      purpura.

PMID- 22409251
TI  - Preventive eye health approach and elimination of avoidable blindness in remote
      rural areas - a vision health guardian approach.

PMID- 22409253
TI  - Temporary impairment of reticulocyte haemoglobin content in subjects with
      community-acquired pneumonia.
AB  - INTRODUCTION: In the case of inflammation, imbalance of iron homoeostasis is
      caused by increased retention of iron within cells of the reticuloendothelial
      system. Iron-restricted erythropoiesis occurs because of decreased availability
      of iron for haemoglobin (Hb) synthesis in erythroid progenitor cells. Deviations
      in reticulocyte haemoglobin (Ret-He) content are investigated together with
      inflammation markers in subjects with community-acquired pneumonia (CAP). Short
      term alterations with regard to Ret-He during and after completing antibiotic
      treatment are investigated. METHODS: A total of 75 patients, classified into
      three subgroups with CURB-65 scores of <=1, 2 and >=3, participated in the study.
      RESULTS: Within the three subgroups, Hb results demonstrate a decline from the
      day of admission until day 4. From day 4, an increase towards higher values is
      observed at day 14. Within 24 h after admission, Ret-He results are situated
      within the lower quartile region of the reference range interval. Until day 4 of
      hospital admission, a steady trend towards a decline of 3-8% is established.
      During antibiotic treatment, an increase in reticulocyte count occurs from 0.039
      +/- 0.014 * 10(12) /L at day 4 to 0.057 +/- 0.020 * 10(12) /L at day 14 (mean +/-
      SD). Recovery of Hb and Ret-He occurs towards values within the reference range.
      CONCLUSION: In subjects with CAP, acute inflammation results in impairment of Ret
      He at an early stage. After onset of pneumonia, decreased results of Ret-He and
      Ret-He/RBC-He ratio are demonstrated, reflecting acute erythropoietic
      dysfunction, which are amongst others caused by functional iron depletion.

PMID- 22409254
TI  - Role of naofen in apoptosis of hepatocytes induced by lipopolysaccharide through
      mitochondrial signaling in rats.
AB  - AIM:   Lipopolysaccharide (LPS) causes apoptosis of hepatocytes, which is
      probably mediated by inflammatory substances released from Kupffer cells (KCs).
      Recently, we have reported that naofen, a newly found intracellular WD40-repeat
      protein, has a role in inducing the apoptosis in HEK293 cells. Hence, the present
      study was undertaken to investigate a role of naofen in the LPS-induced apoptosis
      of rat hepatocytes. METHODS:   Rats were treated with i.v. injections of LPS, and
      livers were extirpated to evaluate expression of naofen and apoptosis. In in
      vitro experiments, hepatocytes and KCs were separately isolated from rat livers.
      The incubation medium for KCs treated with LPS (KC-CM) was used for hepatocyte
      culture. RESULTS:   Intravenous injections of LPS enhanced the expression of
      naofen in the livers. Livers showed terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL)-positive staining, and elevated caspase-3
      activity. In isolated KCs or hepatocytes, LPS hardly affected naofen expression
      and caspase-3 activity, whereas incubation of hepatocytes with KC-CM enhanced
      both naofen expression and caspase-3 activation. Transfection of hepatocyte with
      naofen siRNA prevented such effects of KC-CM, and clearly eliminated KC-CM
      induced reduction of Bcl-2 and Bcl-xL. In contrast, overexpression of naofen in
      hepatocytes downregulated Bcl-2 and Bcl-xL, released cytochrome c from
      mitochondria, and activated caspase-3. CONCLUSION:   These results indicate that
      LPS may induce the hepatic apoptosis in association with enhanced naofen
      expression, and that naofen may mediate the activation of caspase-3 through
      downregulating the Bcl-2 and Bcl-xL expression, and releasing cytochrome c from
      mitochondria to cytoplasm.

PMID- 22409255
TI  - Perturbation of the EphA2-EphrinA1 system in human prostate cancer cells by
      colonic (poly)phenol catabolites.
AB  - The Eph tyrosine kinase receptors and their ephrin ligands play a central role in
      human cancer as their deregulated expression induces tumorigenesis with
      aggressive phenotypes. To evaluate their potential contribution to EphA2-ephrinA1
      modulation, several colonic catabolites of dietary (poly)phenolics, known to be
      generated in vivo, were screened using an ELISA-based binding assay. Some of the
      catabolites inhibited the binding in a dose-dependent manner (IC(50) values from
      0.26 to 43 MUM). Functional studies on prostate adenocarcinoma cells revealed
      that pyrogallol and protocatechuic acid specifically antagonized ephrinA1-Fc
      induced EphA2 phosphorylation at concentrations that were not cytotoxic. The
      active concentrations of pyrogallol appear to be close to what can be reached in
      vivo under physiological conditions. Finally, because of the roles played by the
      Eph-ephrin system not only in cancer development but also in neurodegeneration
      and diabetes, pyrogallol and protocatechuic acid are candidates for more detailed
      functional studies to elucidate their role in these pathophysiological processes.

PMID- 22409256
TI  - Nontargeted nucleotide analysis based on benzoylhistamine labeling-MALDI-TOF/TOF
      MS: discovery of putative 6-oxo-thymine in DNA.
AB  - A method for nontargeted analysis of modified nucleotides in DNA (and RNA) is
      reported based on labeling with benzoylhistamine (BH) followed by MALDI-MS. The
      method provides deoxynucleotide-specific detection, accurate measurement of
      molecular ions, high sensitivity, semiquantitation, and, to the extent studied to
      date, normalization of response within a factor of <3.

PMID- 22409257
TI  - Mechanisms and fitness effects of antibacterial defences in a carrion beetle.
AB  - Parents of many species care for their offspring by protecting them from a wide
      range of environmental hazards, including desiccation, food shortages, predators,
      competitors, and parasites and pathogens. Currently, little is known about the
      mechanisms and fitness consequences of parental defences against bacterial
      pathogens and competitors. Here, we combine approaches from microbiology and
      behavioural ecology to investigate the role and mechanistic basis of
      antibacterial secretions applied to carcasses by parents of the burying beetle
      Nicrophorus vespilloides. This species rears its larvae on vertebrate carcasses,
      where larvae suffer significant fitness costs due to competition with bacterial
      decomposers. We first confirm that anal secretions produced by parents are
      potently bactericidal and that their effects are specific to gram-positive
      bacteria. Next, we identify the source of bacterial killing as a secreted
      lysozyme and show that its concentration changes throughout the breeding cycle.
      Finally, we show that secreted lysozyme is crucial for larval development,
      increasing survival by nearly two-fold compared to offspring reared in its
      absence. These results demonstrate for the first time that anal secretions
      applied to carrion is a form of parental care and expand the mechanistic
      repertoire of defences used by parent insects to protect dependent offspring from
      microbial threats.

PMID- 22409259
TI  - Hydrogen bond energies and cooperativity in substituted calix[n]arenes (n = 4,
      5).
AB  - Hydrogen-bonded interactions in para-substituted calix[n]arenes (CX[n]) (n = 4,
      5) and their thia analogues are analyzed using the recently proposed molecular
      tailoring approach. The cooperative contribution toward the hydrogen-bonding
      network within the CX[5] host is shown to be nearly 5 times larger than that in
      its thia analogue. Hydrogen bond strengths in the O-H...O network are enhanced on
      substitution of an electron-donating group. The cooperativity contributions are
      reflected in the electron density at the bond critical point in the quantum
      theory of atoms in molecules.

PMID- 22409258
TI  - Analysis and elimination of a bias in targeted molecular dynamics simulations of
      conformational transitions: application to calmodulin.
AB  - The popular targeted molecular dynamics (TMD) method for generating transition
      paths in complex biomolecular systems is revisited. In a typical TMD transition
      path, the large-scale changes occur early and the small-scale changes tend to
      occur later. As a result, the order of events in the computed paths depends on
      the direction in which the simulations are performed. To identify the origin of
      this bias, and to propose a method in which the bias is absent, variants of TMD
      in the restraint formulation are introduced and applied to the complex open <->
      closed transition in the protein calmodulin. Due to the global best-fit rotation
      that is typically part of the TMD method, the simulated system is guided
      implicitly along the lowest-frequency normal modes, until the large spatial
      scales associated with these modes are near the target conformation. The
      remaining portion of the transition is described progressively by higher
      frequency modes, which correspond to smaller-scale rearrangements. A
      straightforward modification of TMD that avoids the global best-fit rotation is
      the locally restrained TMD (LRTMD) method, in which the biasing potential is
      constructed from a number of TMD potentials, each acting on a small connected
      portion of the protein sequence. With a uniform distribution of these elements,
      transition paths that lack the length-scale bias are obtained. Trajectories
      generated by steered MD in dihedral angle space (DSMD), a method that avoids best
      fit rotations altogether, also lack the length-scale bias. To examine the
      importance of the paths generated by TMD, LRTMD, and DSMD in the actual
      transition, we use the finite-temperature string method to compute the free
      energy profile associated with a transition tube around a path generated by each
      algorithm. The free energy barriers associated with the paths are comparable,
      suggesting that transitions can occur along each route with similar
      probabilities. This result indicates that a broad ensemble of paths needs to be
      calculated to obtain a full description of conformational changes in
      biomolecules. The breadth of the contributing ensemble suggests that energetic
      barriers for conformational transitions in proteins are offset by entropic
      contributions that arise from a large number of possible paths.

PMID- 22409260
TI  - The influence of emotional stimuli on attention orienting and inhibitory control
      in pediatric anxiety.
AB  - BACKGROUND: Anxiety disorders are highly prevalent in children and adolescents,
      and are associated with aberrant emotion-related attention orienting and
      inhibitory control. While recent studies conducted with high-trait anxious adults
      have employed novel emotion-modified antisaccade tasks to examine the influence
      of emotional information on orienting and inhibition, similar studies have yet to
      be conducted in youths. METHODS: Participants were 22 children/adolescents
      diagnosed with an anxiety disorder, and 22 age-matched healthy comparison youths.
      Participants completed an emotion-modified antisaccade task that was similar to
      those used in studies of high-trait anxious adults. This task probed the
      influence of abruptly appearing neutral, happy, angry, or fear stimuli on
      orienting (prosaccade) or inhibitory (antisaccade) responses. RESULTS: Anxious
      compared to healthy children showed facilitated orienting toward angry stimuli.
      With respect to inhibitory processes, threat-related information improved
      antisaccade accuracy in healthy but not anxious youth. These findings were not
      linked to individual levels of reported anxiety or specific anxiety disorders.
      CONCLUSIONS: Findings suggest that anxious relative to healthy children manifest
      enhanced orienting toward threat-related stimuli. In addition, the current
      findings suggest that threat may modulate inhibitory control during adolescent
      development.

PMID- 22409261
TI  - From adults to children: simulation-based choice of an appropriate sparse
      sampling schedule.
AB  - BACKGROUND: According to the International Conference on Harmonisation guideline
      E11, pharmacokinetic (PK) bridging studies can be applied to support pediatric
      drug development. However, for PK studies in infants and children the sampling
      schedule needs to be optimized to minimize the number of blood samples per
      individual. OBJECTIVE: The aim of this study was to describe how clinical trial
      simulations (CTS) based on adult data were used to select an appropriate sparse
      sampling schedule for a future pediatric population PK (popPK) study. METHODS: A
      popPK model for gadobutrol (Gadovist(r)) was developed using data from a phase I
      study in adults. This model was used for CTS to select the most appropriate
      sparse-sampling schedule that met predefined acceptance criteria. This sampling
      schedule was applied in a pediatric clinical phase I/III study. Non-linear mixed
      effects modeling was used for PK modeling and simulations. RESULTS: An
      appropriate sampling schedule requiring only three blood samples per patient was
      selected and successfully applied in a pediatric study with a gadobutrol standard
      dose of 0.1 mmol/kg bodyweight. A popPK analysis was performed to determine
      individual PK parameters in the pediatric study population. CONCLUSIONS: A priori
      evaluation of selected sampling schedules by simulation from adult data provides
      a useful tool for efficient planning of pediatric studies.

PMID- 22409262
TI  - A randomized phase II trial of apixaban for the prevention of thromboembolism in
      patients with metastatic cancer.
AB  - BACKGROUND: Cancer patients receiving chemotherapy are at increased risk for
      thrombosis. Apixaban, a factor Xa inhibitor, is oral and does not require
      laboratory monitoring. OBJECTIVES: A pilot study was conducted to evaluate
      whether apixaban would be well tolerated and acceptable in cancer patients
      receiving chemotherapy. PATIENTS/METHODS: Subjects receiving either first-line or
      second-line chemotherapy for advanced or metastatic lung, breast,
      gastrointestinal, bladder, ovarian or prostate cancers, cancer of unknown origin,
      myeloma or selected lymphomas were randomized to 5 mg, 10 mg or 20 mg once daily
      of apixaban or placebo in a double-blind manner for 12 weeks. Use of the study
      drug began within 4 weeks of the start of chemotherapy. The primary outcome was
      either major bleeding or clinically relevant non-major (CRNM) bleeding. Secondary
      outcomes included venous thromboembolism (VTE) and grade III or higher adverse
      events related to the study drug. Thirty-two patients received 5 mg, 30 patients
      10 mg, 33 patients 20 mg, and 30 patients placebo. In these groups, there were 0,
      0, 2 and 1 major bleeds, respectively. The corresponding data for CRNM bleeds
      were 1, 1, 2, and 0. The rate of major bleeding in the 93 apixaban patients was
      2.2% (95% confidence interval 0.26-7.5%). There were no fatal bleeds. Three
      placebo patients had symptomatic VTE. CONCLUSIONS: Apixaban was well tolerated in
      our study population. These results support further study of apixaban in phase
      III trials to prevent VTE in cancer patients receiving chemotherapy.

PMID- 22409263
TI  - Flavin-containing monooxygenase 3 gene polymorphisms in Turkish population.
AB  - Flavin-containing monooxygenases (FMOs) represent the second most important human
      monooxygenase system, after cytochrome P450s (CYPs) and catalyze the oxygenation
      of many chemicals containing nitrogen-, sulphur-, phosphorous-, selenium- and
      other nucleophilic heteroatoms. FMO3 is the prominent FMO form in adult human
      liver. For FMO3, both interindividual variability within a single ethnic group
      and variability between ethnic groups have been reported. In our study, three
      prevalent functional FMO3 variants (E158K, V257M, and E308G) were genotyped in
      healthy Turkish people by polymerase chain reaction (PCR)-restriction fragment
      length polymorphism (RFLP) methods. The frequencies of alleles and haplotypes
      were compared with those obtained from different populations. It was found that
      FMO3 158K, 257M and 308G alleles, demonstrate impaired metabolism toward many
      FMO3 substrates, were observed frequently in Turkish population similar to the
      other populations. Also, the frequencies of haplotypes were determined based on
      individual allelic frequencies and it was observed that the most common
      haplotypes were haplotip EVE and KVE (E158K/V257M/E308G), which together
      accounted for 80% of all haplotypes. The obtained data from the present study
      could be useful for further studies assessing sensitivity to therapeutic drugs,
      environmental toxicants and common disease.

PMID- 22409264
TI  - Debunking vaccination myths: strong risk negations can increase perceived
      vaccination risks.
AB  - OBJECTIVE: Information about risks is often contradictory, especially in the
      health domain. A vast amount of bizarre information on vaccine-adverse events
      (VAE) can be found on the Internet; most are posted by antivaccination activists.
      Several actors in the health sector struggle against these statements by negating
      claimed risks with scientific explanations. The goal of the present work is to
      find optimal ways of negating risk to decrease risk perceptions. METHODS: In two
      online experiments, we varied the extremity of risk negations and their source.
      Perception of the probability of VAE, their expected severity (both variables
      serve as indicators of perceived risk), and vaccination intentions. RESULTS:
      Paradoxically, messages strongly indicating that there is "no risk" led to a
      higher perceived vaccination risk than weak negations. This finding extends
      previous work on the negativity bias, which has shown that information stating
      the presence of risk decreases risk perceptions, while information negating the
      existence of risk increases such perceptions. Several moderators were also
      tested; however, the effect occurred independently of the number of negations,
      recipient involvement, and attitude. Solely the credibility of the information
      source interacted with the extremity of risk negation: For credible sources
      (governmental institutions), strong and weak risk negations lead to similar
      perceived risk, while for less credible sources (pharmaceutical industries) weak
      negations lead to less perceived risk than strong negations. CONCLUSIONS: Optimal
      risk negation may profit from moderate rather than extreme formulations as a
      source's trustworthiness can vary.

PMID- 22409265
TI  - Phytoremediation of trichlorophenol by Phase II metabolism in transgenic
      Arabidopsis overexpressing a Populus glucosyltransferase.
AB  - Trichlorophenol (TCP) and its derivatives are introduced into the environment
      through numerous sources, including wood preservatives and biocides.
      Environmental contamination by TCPs is associated with human health risks,
      necessitating the development of cost-effective remediation techniques. Efficient
      phytoremediation of TCP is potentially feasible because it contains a hydroxyl
      group and is suitable for direct phase II metabolism. In this study, we present a
      system for TCP phytoremediation based on sugar conjugation by overexpressing a
      Populus putative UDP-glc-dependent glycosyltransferase (UGT). The enzyme
      PtUGT72B1 displayed the highest TCP-conjugating activity among all reported UGTs.
      Transgenic Arabidopsis demonstrated significantly enhanced tolerances to 2,4,5
      TCP and 2,4,6-TCP. Transgenic plants also exhibited a strikingly higher capacity
      to remove TCP from their media. This work indicates that Populus UGT
      overexpression in Arabidopsis may be an efficient method for phytoremoval and
      degradation of TCP. Our findings have the potential to provide a suitable
      remediation strategy for sites contaminated by TCP.

PMID- 22409266
TI  - Assessing education in pulmonary rehabilitation: the Understanding COPD (UCOPD)
      questionnaire.
AB  - There is currently no questionnaire available that comprehensively assesses
      patients' understanding, self-efficacy and satisfaction with the education
      component of pulmonary rehabilitation. The aim of this study was to develop the
      Understanding COPD (UCOPD) questionnaire. The key stages in the development of
      the UCOPD questionnaire were: (i) Generation of questions, and assessment of face
      and content validity, user-centredness, acceptability and feasibility; (ii)
      Assessment of plain English and readability; (iii) Assessment of structural
      validity; (iv) Assessment of test-retest reliability and internal consistency;
      (v) Assessment of the responsiveness, convergent validity and floor and ceiling
      effects. The UCOPD questionnaire assesses understanding, self-efficacy and use of
      key self-management skills (Section A) and satisfaction (Section B). It has good
      validity and practical properties, and readability was acceptable. It has good
      test-retest reliability (Section A: ICC range: 0.87 to 0.96; Section B: Wilcoxon:
      p > 0.05) and internal consistency (Cronbach's Alpha range: 0.78 to 0.95). It is
      responsive to pulmonary rehabilitation (Mean change: About COPD: 18.26 [12.12 to
      24.40]%, Managing Symptoms 20.94 [13.86 to 28.01]%, Accessing Help and Support
      24.06 [14.53 to 33.60]%, Total 20.59 [14.43 to 26.75]%, p < 0.001). It had a
      moderate correlation with the Bristol COPD Knowledge Questionnaire (BCKQ): pre
      pulmonary rehabilitation: r = 0.41, p = 0.02; post-pulmonary rehabilitation: r =
      0.35, p = 0.047. In conclusion, the UCOPD questionnaire offers the opportunity to
      assess the benefit of the education component of pulmonary rehabilitation in
      terms of its effect on understanding, self-efficacy and satisfaction. Further
      research is needed across different pulmonary rehabilitation settings to
      demonstrate the robustness of the UCOPD questionnaire, and to establish the
      minimum clinically important difference.

PMID- 22409267
TI  - Distribution, elimination, and renal handling of (99m)technetium-Demogastrin 1.
AB  - Radiolabeled cholecystokinin/gastrin (CCK) receptor-targeting peptides are
      promising compounds for radiodiagnosis and radiotherapy of certain malignancies.
      This study evaluated the pharmacokinetic profile of a CCK-2 receptor-specific
      peptide, Demogastrin 1, labeled with technetium-99m ((99m)Tc-Demogastrin 1), in
      rats. To investigate the fate of (99m)Tc-Demogastrin 1 in the rat,
      biodistribution and elimination studies in vivo were performed, and elimination
      parameters in perfused rat liver and kidney were determined. Biodistribution
      studies showed that (99m)Tc-Demogastrin 1 was rapidly cleared from the blood and
      most organs. A significant amount of radioactivity was detected in the CCK-2
      receptor-rich organs, such as the stomach. Low radioactivity was found in the CCK
      1 receptor-rich organs. Radioactivity in bowels and stomach declined relatively
      slowly. High and long-term retention of radioactivity in the kidneys was
      observed. Elimination of (99m)Tc-Demogastrin 1 via the bile was negligible. A
      high and rapid renal excretion was observed in elimination experiments in vivo.
      In the perfused kidney, glomerular filtration was found to be the main renal
      excretion mechanism of (99m)Tc-Demogastrin 1. Demogastrin 1 was distributed
      preferentially to the organs expressing CCK-2 receptors. The decisive elimination
      route of (99m)Tc-Demogastrin 1 in rats was urinary excretion. A high and
      prolonged renal retention may limit potential clinical use of the compound.

PMID- 22409268
TI  - Ponatinib may overcome resistance of FLT3-ITD harbouring additional point
      mutations, notably the previously refractory F691I mutation.
AB  - Fms-like tyrosine kinase (FLT3) mutations are the most frequent mutations in
      patients with acute myeloid leukaemia (AML) that confer a poor prognosis.
      Constitutively active FLT3-ITD (internal tandem duplications) mutations define a
      promising target for therapeutic approaches using small molecule inhibitors.
      However, several point mutations of the FLT3 tyrosine kinase domain (FLT3-TKD)
      have been identified to mediate resistance towards FLT3 tyrosine kinase
      inhibitors (FLT3-TKI), including secondary mutations of FLT3. We investigated the
      cellular effects of the recently characterised FLT3-TKI ponatinib (AP24534) on
      murine myeloid cells transfected with FLT3-ITD with or without additional point
      mutations of the FLT3-TKD including the (so far) multi-resistant F691I mutation.
      Ponatinib effectively induced apoptosis not only in the parental FLT3-ITD cell
      line but also in all stably transfected subclones harbouring additional FLT3-TKD
      point mutations (N676D, F691I or G697R). These observations correlated with a
      strong inhibition of FLT3-ITD and its downstream targets STAT5, AKT and ERK1/2
      upon ponatinib incubation, as determined by Western blotting. We conclude that
      ponatinib represents a promising FLT3-TKI that should be further investigated in
      clinical trials. The targeted therapy of FLT3-ITD-positive AML with ponatinib
      might be associated with a lower frequency of secondary resistance caused by
      acquired FLT3-TKD mutations.

PMID- 22409269
TI  - Selective bladder preservation with curative intent for muscle-invasive bladder
      cancer: a contemporary review.
AB  - Radical cystectomy plus urinary diversion, the reference standard treatment for
      muscle-invasive bladder cancer, associates with high complication rates and
      compromises quality of life as a result of long-term effects on urinary,
      gastrointestinal and sexual function, and changes in body image. As a society
      ages, the number of elderly patients unfit for radical cystectomy as a result of
      comorbidity will increase, and thus the demand for bladder-sparing approaches for
      muscle-invasive bladder cancer will also inevitably increase. Trimodality bladder
      sparing approaches consisting of transurethral resection, chemotherapy and
      radiotherapy (Sigma 55-65 Gy) yield overall survival rates comparable with those
      of radical cystectomy series (50-70% at 5 years), while preserving the native
      bladder in 40-60% of muscle-invasive bladder cancer patients, contributing to an
      improvement in quality of life for such patients. Limitations of the trimodality
      therapy include (i) muscle-invasive bladder cancer recurrence in the preserved
      bladder, which most often arises in the original muscle-invasive bladder cancer
      site; (ii) potential lack of curative intervention for regional lymph nodes; and
      (iii) increased morbidity in the event of salvage radical cystectomy for
      remaining or recurrent disease as a result of high-dose pelvic irradiation.
      Consolidative partial cystectomy with pelvic lymph node dissection followed by
      induction chemoradiotherapy at lower dose (e.g. 40 Gy) is a rational strategy for
      overcoming such limitations by strengthening locoregional control and reducing
      radiation dosage. Molecular profiling of the tumor and functional imaging might
      play important roles in optimal patient selection for bladder preservation.
      Refinement of radiation techniques, intensified concurrent or adjuvant
      chemotherapy, and novel sensitizers, including molecular targeting agent, are
      also expected to improve outcomes and consequently provide more muscle-invasive
      bladder cancer patients with favorable quality of life.

PMID- 22409271
TI  - The busiest of all ribosomal assistants: elongation factor Tu.
AB  - During translation, the nucleic acid language employed by genes is translated
      into the amino acid language used by proteins. The translator is the ribosome,
      while the dictionary employed is known as the genetic code. The genetic
      information is presented to the ribosome in the form of a mRNA, and tRNAs connect
      the two languages. Translation takes place in three steps: initiation,
      elongation, and termination. After a protein has been synthesized, the components
      of the translation apparatus are recycled. During each phase of translation, the
      ribosome collaborates with specific translation factors, which secure a proper
      balance between speed and fidelity. Notably, initiation, termination, and
      ribosomal recycling occur only once per protein produced during normal
      translation, while the elongation step is repeated a large number of times,
      corresponding to the number of amino acids constituting the protein of interest.
      In bacteria, elongation factor Tu plays a central role during the selection of
      the correct amino acids throughout the elongation phase of translation.
      Elongation factor Tu is the main subject of this review.

PMID- 22409272
TI  - Mechanisms of HIV-1 latency post HAART treatment area.

PMID- 22409270
TI  - Antimicrobial peptides: agents of border protection for companion animals.
AB  - Over the past 20 years, there have been significant inroads into understanding
      the roles of antimicrobial peptides in homeostatic functions and their
      involvement in disease pathogenesis. In addition to direct antimicrobial
      activity, these peptides participate in many cellular functions, including
      chemotaxis, wound healing and even determination of canine coat colour. Various
      biological and genetic approaches have helped to elucidate the role of
      antimicrobial peptides with respect to innate immunity and host defense.
      Associations of antimicrobial peptides with various skin diseases, including
      psoriasis, rosacea and atopic dermatitis, have been documented in humans. In the
      longer term, therapeutic modulation of antimicrobial peptide expression may
      provide effective new treatments for disease. This review highlights current
      knowledge about antimicrobial peptides of the skin and circulating leukocytes,
      with particular focus on relevance to physiology and disease in companion
      animals.

PMID- 22409273
TI  - Compound heterozygote condition in beta thalassemia major due to a novel single
      nucleotide deletion (-T) at codon 69 in association with IVS 1-5 (G>C) mutation.

PMID- 22409274
TI  - Interplay between bone marrow and liver in the pathogenesis of hepatic fibrosis.
AB  - Recent advances in the technologies of both molecular biology and regenerative
      medicine have made it possible to identify bone marrow (BM)-derived cells
      migrating into various fibrotic organs including the liver. A number of studies
      have reported that BM-derived cells migrating into fibrotic liver tissue exhibit
      a myofibroblast-like phenotype and may participate in the progression of liver
      fibrosis. On the other hand, it has also been shown that BM-derived cells express
      matrix metalloproteinases and contribute to the regression of experimental liver
      fibrosis. These contradictory results may arise, at least in part, from the
      uncertainty of various different methods that have been used in those studies. In
      this review article, we describe the interplay between BM and liver in the
      progression and regression of liver fibrosis, with an emphasis on the necessity
      of qualified methods with high specificity and sensitivity to evaluate the role
      of BM-derived cells in collagen production.

PMID- 22409275
TI  - Content comparison of questionnaires and scales used in low back pain based on
      the international classification of functioning, disability and health: a
      systematic review.
AB  - PURPOSE: To identify questionnaires and scales that measure functioning and
      disability in low-back pain (LBP) and determine whether the measurements are
      comparable with the International Classification of Functioning, Disability and
      Health (ICFDH). METHODS: We searched MEDLINE, EMBase, CINAHL and PEDro in
      English, and CNKI and Wanfang Data in Chinese in a period from the date of the
      database establishment to September 2010. From the identified literature,
      questionnaires and scales used to assess LBP-related functioning and disability
      were collected and classified. Each item in each questionnaire and scale was
      extracted and classified according to the ICFDH categories. RESULTS: We have
      reviewed 7968 published articles and identified a total of fifteen
      questionnaires. A total of 219 items were analyzed and a total of 354 concepts
      contained in these items and 345 could be linked to ICFDH components, 138 linked
      to body function, 20 to body structure, 174 to activities and participation, and
      13 to environmental factors, and 9 to a non-classifiable cluster. In the body
      functions component, only the single category "sensation of pain" was covered by
      most questionnaires. In the activity and participation component, "changing basic
      body position"; "walking" and "maintaining a body position" were covered by most
      questionnaires. Analyzing individual questionnaires, we found that two
      questionnaires (Clinical Back Pain Questionnaire and Million Disability
      Questionnaire) demonstrate a well-balanced distribution of items across different
      ICFDH components. CONCLUSION: This study may help researchers and clinicians to
      choose the most appropriate questionnaires for a specific purpose as well as help
      compare studies that have used different questionnaires for low back pain
      assessment and provide valuable information on the content quality of these
      questionnaires for them. Furthermore, based on our results, more comprehensive
      and balanced instruments may be developed for more accurate assessment of
      functioning in LBP and perhaps other clinical conditions.

PMID- 22409276
TI  - Improvement in mortality of very low birthweight infants and the changing pattern
      of neonatal mortality: the 50-year experience of one perinatal centre.
AB  - AIM: Neonatology is a relatively new sub-specialty so we aimed to review survival
      data in the context of advances in neonatal care. METHOD: Review of neonatal
      survival for very low birthweight babies over the last 50 years. RESULTS: In the
      data collected from a single tertiary neonatal unit, survival for babies 501-1000
      g improved from below 10% in 1959 to over 60% in 2009. Similarly, survival for
      babies 1001 to 1500 g has improved from approximately 50% to over 90%. During the
      study period, death due to extreme prematurity or cardiorespiratory problems,
      namely respiratory distress syndrome, fell from 90% in 1964 to only 45% of
      neonatal deaths in 2008. CONCLUSION: In addition to reporting the remarkable
      improvement in neonatal survival over this period, we have highlighted items of
      historical context.

PMID- 22409277
TI  - An evaluation of gene-gene interaction between the CYP2C9 and VKORC1 genotypes
      affecting the anticoagulant effect of phenprocoumon and acenocoumarol.
AB  - BACKGROUND: Previous studies have provided contradictory results regarding the
      interaction between the CYP2C9 and VKORC1 genotypes affecting various outcome
      measures. OBJECTIVES: We aimed to provide a definite answer regarding the
      question whether there exists a gene-gene interaction between the CYP2C9 and
      VKORC1 genotypes affecting the anticoagulant effect of phenprocoumon and
      acenocoumarol. PATIENTS/METHODS: The EU-PACT cohort dataset, which contains data
      on 624 phenprocoumon and 471 acenocoumarol patients, was used. Patient
      characteristics, pharmacogenetic data, International Normalized Ratios (INRs) and
      dosages were available. We investigated whether there was an interaction between
      the CYP2C9 and VKORC1 genotypes affecting the maintenance dose, time to severe
      over-anticoagulation and time to achieve stability during the first 180 days of
      phenprocoumon and acenocoumarol therapy, in addition to the effect of the
      separate genotypes. The interaction effect was investigated by adding the product
      term of the CYP2C9 and VKORC1 genotype classes for four different commonly used
      CYP2C9 classifications to the linear regression model - for the outcome measure
      maintenance dose - or to the Cox regression models - for the outcome measures
      time to severe over-anticoagulation and time to achieve stability. RESULTS: No
      significant interactions - all P-values above 0.23 for phenprocoumon and 0.30 for
      acenocoumarol - were observed for all outcome measures. CONCLUSIONS: There are no
      interactions between the CYP2C9 and VKORC1 genotypes affecting the maintenance
      dose, time to severe over-anticoagulation and time to achieve stability for
      phenprocoumon and acenocoumarol.

PMID- 22409278
TI  - Preparation of molecular imprinted hydrophobic polymeric nanoparticles having
      structural memories for lysozyme recognition.
AB  - This study is related to the preparation of lysozyme-imprinted poly(hydroxyethyl
      methacrylate-N-methacryloyl-(L)-tyroptophan methylester) [nano-MIP] nanoparticles
      for purification of lysozyme. Nano-MIP particles were found to be 261 nm in
      diameter with a surface area of 1648 m(2)/g. According to the elemental analysis
      results, the particles contained 0.85 MUmol MATrp/g polymer. The maximum lysozyme
      adsorption capacity was 1182.8 mg/g. Adsorbed lysozyme was desorbed with 94%
      recovery. It was observed that after five adsorption-desorption cycles there was
      no significant loss in adsorption capacity. In order to show the selectivity of
      the Lys-MIP nanoparticles, adsorption of lysozyme, bovine serum albumin (BSA),
      and cytochrome c were investigated.

PMID- 22409279
TI  - Different multiple regeneration capacities of motor and sensory axons in
      peripheral nerve.
AB  - After peripheral nerve injury, axons often project sprouts from the node of
      Ranvier proximal to the damage site. It is well known that one parent axon can
      sprout and maintain several regenerating axons. If enough endoneurial tubes in
      the distal stump are present for the regenerating axons to grow along, then the
      number of mature myelinated nerve fibers in the distal stump will be greater than
      the number in the proximal stump. "Multiple regeneration" is used to describe
      this phenomenon in the peripheral nerve. According to previous studies, a
      prominent nerve containing many axons can be repaired by the multiple
      regenerating axons sprouting from another nerve that contains fewer axons. Most
      peripheral nerves contain a mixture of myelinated motor and sensory axons as well
      as unmyelinated sensory and autonomic axons. In this study, a multiple
      regeneration animal model was developed by bridging the proximal common peroneal
      nerve with the distal common peroneal nerve and the tibial nerve. Differences in
      the multiple regeneration ratio of motor and sensory nerves were evaluated using
      histomorphometry one month after ablating the dorsal root ganglion (DRGs) and
      ventral roots, respectively. The results suggest that the motor nerves have a
      significantly larger multiple regeneration ratio than the sensory nerves at two
      different time points.

PMID- 22409280
TI  - Surface modification of PBT nonwoven fabrics used for blood filtration and their
      blood compatibility study.
AB  - It is necessary to remove residual leukocytes to prevent the blood transfusion
      related adverse reactions. This paper describes a facile approach for the surface
      modification of commercial PBT nonwoven fabrics (PBTNF), used for blood
      filtration, followed by immobilizing polyvinylpyrrolidone (PVP). The whole blood
      filtration results revealed that the five types of PBTNF-PVPs' leucocytes
      retention rates and erythrocyte recovery rates increased to 96% and 92% compared
      with the untreated PBTNF. The blood compatibilities results indicated that PVP
      modified PBTNFs have good blood compatibility, suggesting that PVP-modified PBTNF
      is a very promising blood filter for selective removal of leukocytes.

PMID- 22409282
TI  - Optical manipulation of nano-micro needle array for large volume molecular
      diagnosis.
AB  - Optical vorticesare generated and controlled to form trapping tools in the same
      way as optical tweezers. By using the intense optical vortices generated within
      the PANDA ring resonator, the required atoms/molecules can be trapped and moved
      (transported) dynamically within the wavelength router or network. The advantage
      of the proposed system is that a transmitter and receiver can be formed within
      the same system, which is available for atoms/molecules storage and
      transportation based on methods that have been proposed to deliver drugs into
      cells for specific diagnosis.

PMID- 22409281
TI  - From artificial red blood cells, oxygen carriers, and oxygen therapeutics to
      artificial cells, nanomedicine, and beyond.
AB  - The first experimental artificial red blood cells have all three major functions
      of red blood cells (rbc). However, the first practical one is a simple
      polyhemoglobin (PolyHb) that only has an oxygen-carrying function. This is now in
      routine clinical use in South Africa and Russia. An oxygen carrier with
      antioxidant functions, PolyHb-catalase-superoxide dismutase, can fulfill two of
      the three functions of rbc. Even more complete is one with all three functions of
      rbc in the form of PolyHb-catalase-superoxide dismutase-carbonic anhydrase. The
      most advanced ones are nanodimension artificial rbc with either PEG-lipid
      membrane or PEG-PLA polymer membrane. Extensions into oxygen therapeutics include
      a PolyHb-tyrosinase that suppresses the growth of melanoma in a mice model.
      Another is a PolyHb-fibrinogen that is an oxygen carrier with platelet-like
      function. Research has now extended well beyond the original research on
      artificial rbc into many areas of artificial cells. These include nanoparticles,
      nanotubules, lipid vesicles, liposomes, polymer-tethered lipid vesicles,
      polymersomes, microcapsules, bioencapsulation, nanocapules, macroencapsulation,
      synthetic cells, and others. These are being used in nanotechnology,
      nanomedicine, regenerative medicine, enzyme/gene therapy, cell/stem cell therapy,
      biotechnology, drug delivery, hemoperfusion, nanosensers, and even by some groups
      in agriculture, industry, aquatic culture, nanocomputers, and nanorobotics.

PMID- 22409283
TI  - Effective solid contact for ion-selective electrodes: tetrakis(4
      chlorophenyl)borate (TB-) anions doped nanocluster films.
AB  - We report on a novel material, tetrakis(4-chlorophenyl)borate (TB(-)) anion doped
      nanocluster films, as the solid contact (SC) for producing well-defined,
      electrochemically reversible, and nonpolarizable double interfaces on it.
      Detailed studies have unambiguously revealed that, for the first time, the
      developed SC can fully overcome all the signal stability problems of ion
      selective electrodes (ISEs), offering a reliable and universal platform for the
      development of high quality SC-ISEs. As an exemplification, the developed
      monolayer-protected cluster (MPC) based K(+)-ISEs have advantages of excellent
      analytical performances, e.g., the low potential drift (10.1 +/- 0.3 MUV h(-1)
      over 72 h measured in 0.1 M KCl and 10.8 +/- 0.5 MUV h(-1) over 96 h rechecked in
      0.1 M KCl after 1 month) and the stable and reproducible linear range,
      sensitivity, and standard potential (few changes within the first 6 weeks). This
      evidence suggests that the developed MPC films are the most promising SC
      transducers among all the reported ones to the best of our knowledge.

PMID- 22409284
TI  - The predictive validity of criminogenic needs for male and female offenders:
      comparing the relative impact of needs in predicting recidivism.
AB  - Most instruments used to assess offenders' risk of recidivism were developed and
      validated on male samples. Use of these instruments with female offenders is,
      however, common practice. This use with female offenders implies the assumption
      that the risk of recidivism can be predicted on the basis of the same risk
      factors for women as for men. Yet, this implied gender-neutrality of offender
      risk instruments has been the topic of much debate. This study compared
      criminogenic needs in male and female offenders and their relevance in predicting
      recidivism. A large sample of male and female offenders (N = 16,239) charged with
      a range of index offenses was studied. Results mainly support the gender
      neutrality of existing offender risk and needs assessment. However, results do
      suggest that some criminogenic needs may indeed have a different impact on
      recidivism for men and women. Problems with accommodation, education and work,
      and relationships with friends were more strongly correlated to general
      recidivism in men than in women. For women, difficulties with emotional well
      being had a stronger correlation with recidivism than for men. In addition,
      relative to all other criminogenic needs, problems with emotional well-being were
      more important for women than for men in predicting general as well as violent
      recidivism. However, because the bivariate correlation for female offenders
      between emotional difficulties and recidivism is weak (as it is for male
      offenders), the question remains whether the relative importance of emotional
      difficulties in predicting recidivism in women actually has clinical relevance.

PMID- 22409286
TI  - Structural investigations on sodium-lead borophosphate glasses doped with vanadyl
      ions.
AB  - Electron paramagnetic resonance (EPR), optical absorption, and FT-IR spectra of
      vanadyl ions in the sodium-lead borophosphate (Na(2)O-PbO-B(2)O(3)-P(2)O(5))
      (SLBP) glass system have been studied. EPR spectra of all the glass samples
      exhibit resonance signals characteristic of VO(2+) ions. The spin Hamiltonian
      parameters g and A are found to be independent of the V(2)O(5) content and
      temperature. The values of the spin Hamiltonian parameters indicate that the
      VO(2+) ions in SLBP glasses are present in octahedral sites with tetragonal
      compression. The population difference between Zeeman levels (N) is calculated as
      a function of temperature for an SLBP glass sample containing 1.0 mol % VO(2+)
      ions. From the EPR data, the paramagnetic susceptibility (chi) is calculated at
      different temperatures, and the Curie constant (C) is calculated from the 1/chi
      versus T graph. The optical absorption spectra of the glass samples show two
      absorption bands, and they are attributed to V(3+) and V(4+) ions. The optical
      band gap energy (E(opt)) and Urbach energy (DeltaE) are calculated from their
      ultraviolet absorption edges. It is observed that, as the vanadium ion
      concentration increases, E(opt) decreases and DeltaE increases. The study of the
      IR absorption spectrum depicts the presence of BO(3), BO(4), PO(3), PO(4), and
      VO(5) structural units.

PMID- 22409285
TI  - Thiol-redox antioxidants protect against lung vascular endothelial cytoskeletal
      alterations caused by pulmonary fibrosis inducer, bleomycin: comparison between
      classical thiol-protectant, N-acetyl-L-cysteine, and novel thiol antioxidant,
      N,N'-bis-2-mercaptoethyl isophthalamide.
AB  - Lung vascular alterations and pulmonary hypertension associated with oxidative
      stress have been reported to be involved in idiopathic lung fibrosis (ILF).
      Therefore, here, we hypothesize that the widely used lung fibrosis inducer,
      bleomycin, would cause cytoskeletal rearrangement through thiol-redox alterations
      in the cultured lung vascular endothelial cell (EC) monolayers. We exposed the
      monolayers of primary bovine pulmonary artery ECs to bleomycin (10 ug) and
      studied the cytotoxicity, cytoskeletal rearrangements, and the macromolecule
      (fluorescein isothiocyanate-dextran, 70,000 mol. wt.) paracellular transport in
      the absence and presence of two thiol-redox protectants, the classic water
      soluble N-acetyl-L-cysteine (NAC) and the novel hydrophobic N,N'-bis-2
      mercaptoethyl isophthalamide (NBMI). Our results revealed that bleomycin induced
      cytotoxicity (lactate dehydrogenase leak), morphological alterations (rounding of
      cells and filipodia formation), and cytoskeletal rearrangement (actin stress
      fiber formation and alterations of tight junction proteins, ZO-1 and occludin) in
      a dose-dependent fashion. Furthermore, our study demonstrated the formation of
      reactive oxygen species, loss of thiols (glutathione, GSH), EC barrier
      dysfunction (decrease of transendothelial electrical resistance), and enhanced
      paracellular transport (leak) of macromolecules. The observed bleomycin-induced
      EC alterations were attenuated by both NAC and NBMI, revealing that the novel
      hydrophobic thiol-protectant, NBMI, was more effective at uM concentrations as
      compared to the water-soluble NAC that was effective at mM concentrations in
      offering protection against the bleomycin-induced EC alterations. Overall, the
      results of the current study suggested the central role of thiol-redox in
      vascular EC dysfunction associated with ILF.

PMID- 22409287
TI  - Dimensions of oppositional defiant disorder in 3-year-old preschoolers.
AB  - BACKGROUND: To test the factor structure of oppositional defiant disorder (ODD)
      symptoms and to study the relationships between the proposed dimensions and
      external variables in a community sample of preschool children. METHOD: A sample
      of 1,341 3-year-old preschoolers was randomly selected and screened for a double
      phase design. In total, 622 families were assessed with a diagnostic semi
      structured interview and questionnaires on psychopathology, temperament and
      executive functioning completed by parents and teachers. RESULTS: Using
      categorical and dimensional symptoms of ODD it was possible to confirm, cross
      informant and cross-method, distinct dimensions for defining the structure of
      ODD: one made up of irritable and headstrong and the other of negative affect,
      oppositional behaviour and antagonistic behaviour. Specific associations with DSM
      IV disorders were found, and irritable was associated with anxiety disorders,
      whereas headstrong was associated with disruptive disorders, including aggressive
      and non-aggressive CD symptoms. Also, negative affect was associated with anxiety
      disorders and non-aggressive CD symptoms, oppositional behaviour with disruptive
      disorders and aggressive CD symptoms, and antagonistic behaviours with disruptive
      disorders and, in boys, with mood disorders. The dimensions correlated with
      specific scales of psychopathology, temperament and executive functioning.
      CONCLUSIONS: Oppositional defiant disorder is a heterogeneous disorder from
      preschool age. Different dimensions, with moderate to acceptable reliability and
      convergent and discriminant validity with other psychological constructs, can be
      identified early in life.

PMID- 22409288
TI  - Detecting motor vehicle travel in accelerometer data.
AB  - Chronic Obstructive Pulmonary Disease (COPD) frequently has a significant impact
      on patients' everyday activity. Because of this, accurate measurement of daily
      activity is of particular interest. Although accelerometers are an objective
      means of measuring daily activity, these devices sense vibrations and erroneously
      score motor vehicle travel (MVT) as moderate physical activity. It is the
      objective of this study to develop a new method to analyze accelerometry data
      that would accurately classify MVT as non-acceleration, or sitting/standing. As
      sitting/standing has a different pattern of count-to-count variability than
      walking, we hypothesized that a rolling standard deviation (RSD), which is a
      measurement of volatility in the data, would more accurately classify periods of
      MVT than analysis based on activity counts alone. Twenty-two subjects with COPD
      were studied. A training set of 15% of the dataset was used to establish an RSD
      threshold during MVT based on the upper 95%-confidence interval. The accuracy of
      the RSD thresholds were tested and presented as sensitivity, specificity and
      receiver operating curves. Results demonstrated high sensitivity and specificity
      suggesting that the RSD not only accurately classified MVT, but had a low rate of
      misclassification. The RSD analysis scored more MVT as sitting/standing than
      assessment by VMU alone. The accuracy of accelerometers to define the profile of
      daily activity in sedentary populations, such as those with COPD, is greatly
      improved.

PMID- 22409289
TI  - Preservation of (-)-epigallocatechin-3-gallate antioxidant properties loaded in
      heat treated beta-lactoglobulin nanoparticles.
AB  - (-)-Epigallocatechin-3-gallate (EGCG) was loaded in heat treated beta
      lactoglobulin (beta-Lg) for the preservation of antioxidant activity. The effects
      of pH (2.5-7.0), the heating temperature of beta-Lg (30-85  degrees C), the molar
      ratio of beta-Lg to EGCG (1:2-1:32), and the beta-Lg concentration (1-10 mg/mL)
      on the properties of beta-Lg-EGCG complexes were studied. All four factors
      significantly influenced the particle size, the zeta-potential, and the
      entrapment efficiency of EGCG and EGCG loading in beta-Lg particles. A stable and
      clear solution system could be obtained at pH 6.4-7.0. The highest protection of
      EGCG antioxidant activity was obtained with beta-Lg heated at 85  degrees C and
      the molar ratio of 1:2 (beta-Lg: EGCG). beta-Lg-EGCG complexes were found to have
      the same secondary structure as native beta-Lg.

PMID- 22409290
TI  - Cost effectiveness of pharmacological maintenance treatment for chronic
      obstructive pulmonary disease: a review of the evidence and methodological
      issues.
AB  - BACKGROUND: Over 200 million people have chronic obstructive pulmonary disease
      (COPD) worldwide. The number of disease-year equivalents and deaths attributable
      to COPD are high. Guidelines for the pharmacological treatment of the disease
      recommend an individualized step-up approach in which treatment is intensified
      when results are unsatisfactory. OBJECTIVE: Our objective was to present a
      systematic review of the cost effectiveness of pharmacological maintenance
      treatment for COPD and to discuss the methodological strengths and weaknesses of
      the studies. METHODS: A systematic literature search for economic evaluations of
      drug therapy in COPD was performed in MEDLINE, EMBASE, the Economic Evaluation
      Database of the UK NHS (NHS-EED) and the European Network of Health Economic
      Evaluation Databases (EURONHEED). Full economic evaluations presenting both costs
      and health outcomes were included. RESULTS: A total of 40 studies were included
      in the review. Of these, 16 were linked to a clinical trial, 14 used Markov
      models, eight were based on observational data and two used a different approach.
      The few studies on combining short-acting bronchodilators were consistent in
      finding net cost savings compared with monotherapy. Studies comparing inhaled
      corticosteroids (ICS) with placebo or no maintenance treatment reported
      inconsistent results. Studies comparing fluticasone with salmeterol consistently
      found salmeterol to be more cost effective. The cost-effectiveness studies of
      tiotropium versus placebo, ipratropium or salmeterol pointed towards a reduction
      in total COPD-related healthcare costs for tiotropium in many but not all
      studies. All of these studies reported additional health benefits of tiotropium.
      The cost-effectiveness studies of the combination of inhaled long-acting beta2
      agonists and ICS all report additional health benefits at an increase in total
      COPD-related costs in most studies. The cost-per-QALY estimates of this
      combination treatment vary widely and are very sensitive to the assumptions on
      mortality benefit and time horizon. CONCLUSIONS: The currently available economic
      evaluations indicate differences in cost effectiveness between COPD maintenance
      therapies, but for a more meaningful comparison of results it is important to
      improve the consistency with respect to study methodology and choice of
      comparator.

PMID- 22409291
TI  - Cost effectiveness of anticoagulation in acute coronary syndromes.
AB  - BACKGROUND: The benefit of unfractionated heparin (UFH) added to aspirin in
      patients with acute coronary syndromes (ACS) was described more than 20 years
      ago. Ever since, a wide variety of anticoagulant drugs have become available for
      clinical use, including low-molecular-weight heparins (LMWH), direct thrombin
      inhibitors and selective factor Xa inhibitors. OBJECTIVE: The aim of this study
      was to critically review the available evidence on the cost and incremental cost
      effectiveness of anticoagulants in patients with ACS. METHODS: Studies were
      identified using specialist databases (UK NHS Economic Evaluation Database [NHS
      EED] and Cost-Effectiveness Analysis [CEA] Registry), PubMed and the reference
      lists of recovered articles. Only studies based on randomized controlled trials
      were considered for inclusion. Finally, 22 studies were included in the review.
      RESULTS: Enoxaparin is the only LMWH that has been shown to reduce the risk of
      death or myocardial infarction in patients with non-ST-elevation ACS (NSTE-ACS).
      In economic studies based on the ESSENCE trial conducted in the late 1990s,
      enoxaparin was consistently associated with a lower risk of coronary events, a
      reduction in the number of revascularization procedures and a lower cost per
      patient than UFH. However, these results refer to patients managed
      conservatively, with little use of thienopyridines and glycoprotein IIb/IIIa
      inhibitors, and the results are difficult to extrapolate to moderate-to-high-risk
      patients managed with the present day early invasive strategy. Available studies
      of LMWH in ACS with persistent elevation of ST-segment (STE-ACS) are limited to
      patients treated with thrombolysis. In this scenario, enoxaparin was shown to be
      a dominant alternative compared with UFH in a study based on the ASSENT-3 study
      and was considered an economically attractive alternative in three studies based
      on the ExTRACT-TIMI 25 study. However, these results should be interpreted
      cautiously due to the heterogeneity of the supportive randomized trials and the
      possible underestimation of bleeding costs. The effectiveness and safety of
      bivalirudin, a direct thrombin inhibitor, were evaluated in the ACUITY study
      (NSTE-ACS patients managed invasively) and the HORIZONS-AMI study (STE acute
      myocardial infarction patients planned for primary percutaneous coronary
      intervention). Bivalirudin monotherapy was not inferior to heparin plus a
      glycoprotein IIb/IIIa inhibitor and reduced the risk of major bleeding. The
      economic evaluations based on these studies suggest that bivalirudin is an
      attractive alternative to heparin plus a glycoprotein-IIb/IIIa inhibitor. In the
      OASIS-5 trial, compared with enoxaparin, fondaparinux reduced the mortality in
      patients with NSTE-ACS, probably because of a reduced risk of bleeding. In three
      economic evaluations of fondaparinux versus enoxaparin based on this trial,
      fondaparinux was the dominant strategy in two of them, and still economically
      attractive in a third. Taken as a whole, the usefulness of economic studies of
      anticoagulants in patients with ACS is undermined by the quality of the evidence
      about their effectiveness and safety; the narrow spectrum of the analysed
      scenarios; the lack of economic evaluations based on systematic reviews; the
      limitations of sensitivity analyses reported by the available economic
      evaluations; and their substantial risk of commercial bias. CONCLUSIONS: The
      available studies suggest that enoxaparin is an economically attractive
      alternative compared with UFH in patients with NSTE-ACS treated conservatively
      and STE-ACS patients treated with thrombolysis. Bivalirudin in patients with ACS
      treated invasively is cost effective compared with heparin plus a glycoprotein
      IIb/IIIa inhibitor. In patients with NSTE-ACS, fondaparinux is cost effective
      compared with enoxaparin. The usefulness of these results for decision making in
      contemporary clinical practice is limited due to problems of internal and
      external validity.

PMID- 22409292
TI  - Selecting a mix of prevention strategies against cervical cancer for maximum
      efficiency with an optimization program.
AB  - BACKGROUND: Screening and vaccination against human papillomavirus (HPV) can
      protect against cervical cancer. Neither alone can provide 100% protection.
      Consequently it raises the important question about the most efficient
      combination of screening at specified time intervals and vaccination to prevent
      cervical cancer. OBJECTIVE: Our objective was to identify the mix of cervical
      cancer prevention strategies (screening and/or vaccination against HPV) that
      achieves maximum reduction in cancer cases within a fixed budget. METHODS: We
      assessed the optimal mix of strategies for the prevention of cervical cancer
      using an optimization program. The evaluation used two models. One was a Markov
      cohort model used as the evaluation model to estimate the costs and outcomes of
      52 different prevention strategies. The other was an optimization model in which
      the results of each prevention strategy of the previous model were entered as
      input data. The latter model determined the combination of the different
      prevention options to minimize cervical cancer under budget, screening coverage
      and vaccination coverage constraints. We applied the model in two countries with
      different healthcare organizations, epidemiology, screening practices, resource
      settings and treatment costs: the UK and Brazil. 100,000 women aged 12 years and
      above across the whole population over a 1-year period at steady state were
      included. The intervention was papanicolaou (Pap) smear screening programmes
      and/or vaccination against HPV with the bivalent HPV 16/18 vaccine (Cervarix(r)
      [Cervarix is a registered trademark of the GlaxoSmithKline group of companies]).
      The main outcome measures were optimal distribution of the population between
      different interventions (screening, vaccination, screening plus vaccination and
      no screening or vaccination) with the resulting number of cervical cancer and
      associated costs. RESULTS: In the base-case analysis (= same budget as today),
      the optimal prevention strategy would be, after introducing vaccination with a
      coverage rate of 80% in girls aged 12 years and retaining screening coverage at
      pre-vaccination levels (65% in the UK, 50% in Brazil), to increase the screening
      interval to 6 years (from 3) in the UK and to 5 years (from 3) in Brazil. This
      would result in a reduction of cervical cancer by 41% in the UK and by 54% in
      Brazil from pre-vaccination levels with no budget increase. Sensitivity analysis
      shows that vaccination alone at 80% coverage with no screening would achieve a
      cervical cancer reduction rate of 20% in the UK and 43% in Brazil compared with
      the pre-vaccination situation with a budget reduction of 30% and 14%,
      respectively. In both countries, the sharp reduction in cervical cancer is seen
      when the vaccine coverage rate exceeds the maximum screening coverage rate, or
      when screening coverage rate exceeds the maximum vaccine coverage rate, while
      maintaining the budget. As with any model, there are limitations to the value of
      predictions depending upon the assumptions made in each model. CONCLUSIONS:
      Spending the same budget that was used for screening and treatment of cervical
      cancer in the pre-vaccination era, results of the optimization program show that
      it would be possible to substantially reduce the number of cases by implementing
      an optimal combination of HPV vaccination (80% coverage) and screening at pre
      vaccination coverage (65% UK, 50% Brazil) while extending the screening interval
      to every 6 years in the UK and 5 years in Brazil.

PMID- 22409293
TI  - Transfer and subsequent growth and metabolism of Lactobacillus plantarum in
      orange juice medium during storage at 4 and 30 degrees C.
AB  - AIM:   To investigate the physicochemical changes produced from growth and
      metabolism of Lactobacillus plantarum N4 in orange juice medium stored at 4 and
      30 degrees C after transferring from artificially inoculated oranges peel during
      extraction. METHODS AND RESULTS:   Lower than 2.0% of total of the N4 strain was
      recovered in juice extracted from inoculated oranges (about of 10(9 ) CFU ml(-1)
      ) under assayed conditions. After that, the N4 strain grew 2.43 +/- 0.09 log
      cycles in 48 h at 30 degrees C. Sugars such as glucose and fructose and l-malic
      and citric acids were utilized, although at different rates and extent, yielding
      significant lactate and acetate amounts with a concomitant pH reduction. Ethanol,
      diacetyl, acetoin or 2,3 butilenglicol were undetected. During juice storage at 4
      degrees C bacterial counts, sugars composition and pH remained significantly
      unchanged as well as its sensory attributes. CONCLUSION:   The transfer rate of
      L. plantarum N4 to freshly squeezed juice under adequate hygienic condition was
      low. At 30 degrees C, the micro-organism rapidly initiated growth, producing
      acids but not butter flavour compounds neither ethanol. SIGNIFICANCE AND IMPACT
      OF THE STUDY:   The ability of this strain to survive in refrigerated juice
      without cause spoilage warrants further investigation to explore its potential
      use for biotechnology applications.

PMID- 22409294
TI  - Role of intravitreal inflammatory cytokines and angiogenic factors in
      proliferative diabetic retinopathy.
AB  - OBJECTIVE: Inflammatory reaction has been shown to involve the progress of type 2
      (non-insulin-dependent) diabetes. We, therefore, examined the effects of
      inflammatory cytokines and angiogenic factors in the pathogenesis of
      proliferative diabetic retinopathy (PDR) in type 2 diabetes. PATIENTS AND
      METHODS: Vitreous fluid samples were obtained by vitrectomy from 62 eyes of PDR
      patients with type 2 diabetes and from 20 eyes of age-matched non-diabetic
      patients. The concentrations of interleukin 1 beta (IL1B), IL6, IL8, IL10,
      chemokine (C-C motif) ligand 2 (CCL2), endothelin 1 (EDN1), vascular endothelial
      growth factor (VEGF), and tumor necrosis factor (TNF) in the vitreous samples
      were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The
      concentrations of LI1B, IL6, IL8, CCL2, EDN1, VEGF, and TNF in the vitreous
      samples were considerably higher in PDR patients in comparison with the controls.
      However, the level of IL10 in PDR patients was similar to that obtained in the
      controls. Analysis of the correlations of the studied factors revealed the
      correlation of VEGF and IL6, VEGF and EDN1, IL8 and CCL2, and EDN1 and TNF in PDR
      patients. In addition, a significant positive correlation was observed between
      vitreous TNF as well as EDN1 and serum HbA(1)c levels in PDR patients.
      CONCLUSIONS: The inflammatory cytokines and angiogenic factors IL1B, IL6, IL8,
      CCL2, EDN1, VEGF, and TNF are increased in the vitreous of PDR patients without
      an increase in IL-10. These results add support to the role of inflammatory
      cytokines and angiogenic factors in the genesis of PDR. Understanding the
      implication of these cytokines may provide diagnostic tools and therapeutic
      targets for treatment and prevention of PDR.

PMID- 22409295
TI  - Chemoimmunotherapy with ofatumumab in combination with CHOP in previously
      untreated follicular lymphoma.
AB  - An international, Phase II trial was conducted to assess two doses of ofatumumab,
      a human CD20 monoclonal antibody, combined with cyclophosphamide (750 mg/m(2) ),
      doxorubicin (50 mg/m(2) ), prednisone (100 mg days 3-7) and vincristine (1.4
      mg/m(2) ) (O-CHOP), as frontline treatment for follicular lymphoma (FL). 59
      patients with previously untreated FL were randomized to ofatumumab 500 mg (n =
      29) or 1000 mg (n = 30) day 1, with CHOP on day 3 every 3 weeks for six cycles.
      Median duration of FL was 0.1 years for both dose groups; 34% and 38% of patients
      had high-risk Follicular Lymphoma International Prognostic Index (FLIPI) scores
      in the 500- and 1000-mg dose groups, respectively. Overall response rate was 90%
      for the 500-mg group and 100% for the 1000-mg group. 62% of patients achieved
      complete response (CR)/unconfirmed CR (CRu). 76% of patients with FLIPI score 3-5
      attained CR/CRu. Longer follow-up time is needed for analysis of survival end
      points. The most common Common Terminology Criteria grade 3-4 investigator
      reported adverse events were leucopenia (29%) and neutropenia (22%). No deaths
      have been reported. O-CHOP was safe and efficacious in patients with previously
      untreated FL, including high-risk FLIPI groups. This trial was registered at
      www.clinicaltrials.gov (NCT00494780).

PMID- 22409296
TI  - Portal hypertension in children: expert pediatric opinion on the report of the
      Baveno v Consensus Workshop on Methodology of Diagnosis and Therapy in Portal
      Hypertension.
AB  - Complications of portal hypertension in children lead to significant morbidity
      and are a leading indication for consideration of liver transplantation.
      Approaches to the management of sequelae of portal hypertension are well
      described for adults and evidence-based approaches have been summarized in
      numerous meta-analyses and conferences. In contrast, there is a paucity of data
      to guide the management of complications of portal hypertension in children. An
      international panel of experts was convened on April 8, 2011 at The Children's
      Hospital of Pittsburgh of UPMC to review and adapt the recent report of the
      Baveno V Consensus Workshop on the Methodology of Diagnosis and Therapy in Portal
      Hypertension to the care of children. The opinions of that expert panel are
      reported.

PMID- 22409297
TI  - Two novel acentric borate fluorides: M3B6O11F2 (M = Sr, Ba).
AB  - Two novel, noncentrosymmetric borate fluorides, Sr(3)B(6)O(11)F(2) and
      Ba(3)B(6)O(11)F(2), have been synthesized hydrothermally and their structures
      determined. The compounds are isostructural, crystallizing in space group P2(1),
      having lattice parameters of a = 6.4093 (13) A, b = 8.2898 (17) A, c = 9.3656
      (19) A, and beta = 101.51 (3) degrees  for Sr(3)B(6)O(11)F(2) and a = 6.5572 (13)
      A, b = 8.5107 (17) A, c = 9.6726 (19) A, and beta = 101.21 (3) degrees  for
      Ba(3)B(6)O(11)F(2). The structure consists of a complex triple-ring borate
      framework having aligned triangular [BO(3)] groups that impart polarity. Fluorine
      atoms are bound only to the alkaline-earth metals and are not part of the borate
      framework, resulting in a vastly different structure from those of the hydrated
      borates Sr(3)B(6)O(11)(OH)(2) and Ba(3)B(6)O(11)(OH)(2) with similar formulas.
      The title compounds are transparent to nearly 200 nm, making them potentially
      useful for deep-ultraviolet nonlinear-optical applications.

PMID- 22409298
TI  - Editorial comment to clinical outcome analysis of male and female genital burn
      injuries: a 15-year experience at a level-1 burn center.

PMID- 22409299
TI  - Anticancer therapy-induced adverse events: practicing damage control.

PMID- 22409301
TI  - African fluid bolus study: implications for practice.
AB  - The Fluid Expansion as Supportive Therapy (FEAST) trial in an African setting
      without intensive care facilities found that bolus fluid therapy for severe
      infections (including malaria and viral infections) resulted in a significantly
      higher mortality than those not given a bolus. This was a high-quality study of
      3170 children with 48 h mortality as the primary outcome. Despite the different
      setting and diseases than in a developed country context, it could be argued that
      this study calls into question the wisdom of bolus fluid regimes for sepsis, and
      perhaps even the concept of 'compensated shock' in the Advanced Paediatric Life
      Support protocol. Some have tried to attack the ethics of the study, but this is
      unjustified. The implications for paediatric practice in Africa are that
      intravenous fluids need to be monitored more closely, and the practice of giving
      boluses to every 'query septic infant and child' needs to be examined more
      critically.

PMID- 22409300
TI  - Translocation of E. coli RecQ helicase on single-stranded DNA.
AB  - A member of the SF2 family of helicases, Escherichia coli RecQ, is involved in
      the recombination and repair of double-stranded DNA breaks and single-stranded
      DNA (ssDNA) gaps. Although the unwinding activity of this helicase has been
      studied biochemically, the mechanism of translocation remains unclear. To this
      end, using ssDNA of varying lengths, the steady-state ATP hydrolysis activity of
      RecQ was analyzed. We find that the rate of ATP hydrolysis increases with DNA
      length, reaching a maximum specific activity of 38 +/- 2 ATP/RecQ/s. Analysis of
      the rate of ATP hydrolysis as a function of DNA length implies that the helicase
      has a processivity of 19 +/- 6 nucleotides on ssDNA and that RecQ requires a
      minimal translocation site size of 10 +/- 1 nucleotides. Using the T4 phage
      encoded gene 32 protein (G32P), which binds ssDNA cooperatively, to decrease the
      lengths of ssDNA gaps available for translocation, we observe a decrease in the
      rate of ATP hydrolysis activity that is related to lattice occupancy. Analysis of
      the activity in terms of the average gap sizes available to RecQ on the ssDNA
      coated with G32P indicates that RecQ translocates on ssDNA on average 46 +/- 11
      nucleotides before dissociating. Moreover, when bound to ssDNA, RecQ hydrolyzes
      ATP in a cooperative fashion, with a Hill coefficient of 2.1 +/- 0.6, suggesting
      that at least a dimer is required for translocation on ssDNA. We present a
      kinetic model for translocation by RecQ on ssDNA based on this characterization.

PMID- 22409302
TI  - Putative early manifestations of bipolar II disorder emerge later in the initial
      prodrome than manifestations hypothesized to be unrelated: an exploratory study.
AB  - AIM: Symptom instances characterized as episodic or chronic, and as exaggerated
      responses to life events or inexplicable (e.g. mood swings,
      irritability/aggressiveness), may be the most likely early manifestations of the
      first episode of bipolar II disorder (BD-II). Assuming that symptoms that emerge
      late in the prodrome, to a larger extent, are early manifestations of the
      disorder itself, we explore the time of onset and the duration of instances
      classified as 'likely', 'possible' and 'unlikely' early manifestations. METHODS:
      Retrospective interviews of 15 BD-II patients and 22 family members. RESULTS:
      'Likely' early manifestations do, to a larger extent than other symptom
      instances, emerge late in the prodrome. The mean time interval between symptom
      onset and the first episode is shorter for the 'likely' than for the 'unlikely'
      early manifestations but is similar to the 'possible' ones. CONCLUSIONS: Symptom
      instances classified as 'likely' early manifestations may be the most useful to
      prospectively predict BD-II.

PMID- 22409303
TI  - Contactless NMR spectroscopy on a chip.
AB  - Inductively coupled planar resonators offer convenient integration of high
      resolution NMR spectroscopy with microfluidic lab-on-a-chip devices. Planar
      spiral resonators are fabricated lithographically either by gold electroplating
      or by etching Cu laminated with polyimide. Their performance is characterized by
      NMR imaging as well as spectroscopy. A single-scan limit of detection LOD(t) =
      0.95 nmol s(1/2) was obtained from sample volumes around 1 MUL. The sensitivity
      of this approach is similar to that obtained by microstripline and microslot
      probes.

PMID- 22409304
TI  - Correlates of the CBCL-dysregulation profile in preschool-aged children.
AB  - BACKGROUND: A growing literature indicates that the Child Behavior Checklist
      Dysregulation Profile (CBCL-DP) identifies youths with heightened risk for severe
      psychopathology, comorbidity, and impairment. However, this work has focused on
      school-age children and adolescents; no studies have examined whether preschool
      aged children with the CBCL-DP exhibit a similar constellation of problems.
      METHOD: Using a community sample of preschoolers, we compared children with (N =
      61) and without (N = 488) the CBCL-DP on a broad range of variables assessed
      using multiple methods. RESULTS: Univariate analyses revealed numerous
      differences between children with the CBCL-DP and their peers on psychiatric
      symptomatology, temperament, parenting behavior, and parental personality,
      psychopathology, and marital functioning. In multivariate analyses, children with
      the CBCL-DP exhibited greater temperamental negative affectivity and lower
      effortful control. They also had more depressive and oppositional defiant
      symptoms, as well as greater functional impairment. Parents of CBCL-DP children
      reported engaging in more punitive, controlling parenting behavior than parents
      of non-profile children. CONCLUSIONS: In a non-clinical sample of preschoolers,
      the CBCL-DP is associated with extensive emotional and behavioral dysregulation
      and maladaptive parenting.

PMID- 22409306
TI  - Comparative mutant prevention concentration and mechanism of resistance to
      veterinary fluoroquinolones in Staphylococcus pseudintermedius.
AB  - BACKGROUND: The problem of antibacterial drug resistance is increasing worldwide,
      in part due to the therapeutic concentrations currently used based on the minimal
      inhibitory concentration (MIC) as a measure of potency are often the very
      concentrations required to selectively enrich the resistant mutant portion of the
      population. A mutant prevention concentration (MPC)-based dosing strategy is
      suggested to improve the therapeutic outcome based on the MIC. OBJECTIVE: Our aim
      was to investigate the MPC and mechanism of resistance to various
      fluoroquinolones using recent Staphylococcus pseudintermedius isolates from
      canine pyoderma. METHODS: The broth microdilution method for MIC and a series of
      agar plates containing different concentrations of fluoroquinolones were
      inoculated with ~10(10) colony-forming units of the bacterial culture for MPC
      were used. PCR was used to identify mutation in the resistant isolates. RESULTS:
      The rank order of potency based on MIC and MPC was ciprofloxacin = enrofloxacin
      >= marbofloxacin > difloxacin >= orbifloxacin. Integrating our data with reported
      pharmacokinetic data at the recommended dose ranges revealed that only high doses
      of ciprofloxacin, enrofloxacin and marbofloxacin could achieve a maximal plasma
      concentration (C(max)) greater than the MPC of 90% of isolates (C(max)/MPC(90)).
      The overall rank of potency against S. pseudintermedius, based on C(max)/MIC,
      C(max)/MPC, the area under concentration-time curve (AUC)/MIC and AUC/MPC values,
      was in decreasing order: enrofloxacin > ciprofloxacin >= marbofloxacin >=
      orbifloxacin = difloxacin. Sequencing of the quinolone resistant determining
      region of gyrA, gyrB, grlA and grlB of resistant strains showed a base-pair
      substitution in both gyrA and gyrB that resulted in Ser-84 to Leu and Ser-80 to
      Arg amino acid changes, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: High
      doses of ciprofloxacin, enrofloxacin and marbofloxacin could minimize the
      selection of resistant mutants, whereas the possibility of selecting mutants with
      the conventional doses of difloxacin and orbifloxacin, and low clinical doses of
      all fluoroquinolones, seems high.

PMID- 22409307
TI  - Identification of a novel glycoside, leptosin, as a chemical marker of manuka
      honey.
AB  - As a preliminary study, we have found that honey from manuka (Leptospermum
      scoparium) in New Zealand inhibits myeloperoxidase (MPO) activity. In this study,
      using a chromatographic technique, we isolated two active compounds for MPO
      inhibition from manuka honey. One is methyl syringate (MSYR), and the other was
      identified as a novel glycoside of MSYR, methyl syringate 4-O-beta-D-gentiobiose,
      which has been named "leptosin" after the genus Leptospermum . The amount of the
      glycoside ranged from 0.2 to 1.2 MUmol/g honey. Leptosin was only found in honeys
      from the Oceania region, and abundantly in manuka honey including jelly bush
      honey from Leptospermum polygalifolium in Australia. Therefore, leptosin may be a
      good chemical marker for manuka honey. Interestingly, the concentration of
      leptosin in manuka honey was positively correlated with the unique manuka factor
      (UMF) value, which is expressed as phenol equivalents of its bactericidal
      activity.

PMID- 22409308
TI  - Flexible nanocrystal-coated glass fibers for high-performance thermoelectric
      energy harvesting.
AB  - Recent efforts on the development of nanostructured thermoelectric materials from
      nanowires (Boukai, A. I.; et al. Nature 2008, 451, (7175), 168-171; Hochbaum, A.
      I.; et al. Nature 2008, 451, (7175), 163-167) and nanocrystals (Kim, W.; et al.
      Phys. Rev. Lett. 2006, 96, (4), 045901; Poudel, B.; et al. Science 2008, 320,
      (5876), 634-638; Scheele, M.; et al. Adv. Funct. Mater. 2009, 19, (21), 3476
      3483; Wang, R. Y.; et al. Nano Lett. 2008, 8, (8), 2283-2288) show the comparable
      or superior performance to the bulk crystals possessing the same chemical
      compositions because of the dramatically reduced thermal conductivity due to
      phonon scattering at nanoscale surface and interface. Up to date, the majority of
      the thermoelectric devices made from these inorganic nanostructures are
      fabricated into rigid configuration. The explorations of truly flexible composite
      based flexible thermoelectric devices (See, K. C.; et al. Nano Lett. 2010, 10,
      (11), 4664-4667) have thus far achieved much less progress, which in principle
      could significantly benefit the conversion of waste heat into electricity or the
      solid-state cooling by applying the devices to any kind of objects with any kind
      of shapes. Here we report an example using a scalable solution-phase deposition
      method to coat thermoelectric nanocrystals onto the surface of flexible glass
      fibers. Our investigation of the thermoelectric properties yields high
      performance comparable to the state of the art from the bulk crystals and proof
      of-concept demonstration also suggests the potential of wrapping the
      thermoelectric fibers on the industrial pipes to improve the energy efficiency.

PMID- 22409309
TI  - A lower starting dose of eltrombopag is efficacious in Japanese patients with
      previously treated chronic immune thrombocytopenia.
AB  - BACKGROUND: Eltrombopag is an oral, non-peptide thrombopoietin receptor agonist
      that has shown efficacy and safety in chronic immune thrombocytopenia (ITP).
      However, ethnic differences in eltrombopag exposure have been reported: area
      under the curve exposure to eltrombopag was 87% greater among ITP patients of
      East Asian descent than among ITP patients of non-East Asian ITP descent.
      OBJECTIVES: To evaluate the efficacy and safety of eltrombopag by using, in
      Japanese ITP patients, lower starting (12.5 mg) and maximum (50 mg) doses of
      eltrombopag than the standard starting (50 mg) and maximum (75 mg) doses approved
      in the USA and Europe. PATIENTS: We examined 23 Japanese patients with previously
      treated chronic ITP with a platelet count of < 30,000 MUL(-1) in a multicenter
      study comprising a randomized, double-blind, placebo-controlled phase for 6-week
      evaluation (15 eltrombopag, and eight placebo) and an open-label phase for 6
      month evaluation (23 eltrombopag). RESULTS AND CONCLUSIONS: The response rate
      (platelet count of >= 50,000 MUL(-1) ) at week 6 of the 6-week double-blind phase
      was 60% in eltrombopag-treated patients and 0% in placebo-treated patients. Ten
      of 23 patients (43.5%) responded for >= 75% of predefined assessment visits
      during the 6-month open-label phase. Notably, 22% (5/23) of patients responded to
      12.5 mg of eltrombopag, which was administered within the first 3 weeks of
      eltrombopag treatment. Bleeding decreased with eltrombopag treatment as compared
      with baseline. Eltrombopag was generally well tolerated; one patient experienced
      a transient ischemic attack on day 9. Eltrombopag (12.5-50 mg) is effective for
      the management of Japanese patients with chronic ITP (NCT00540423).

PMID- 22409310
TI  - Biochemical and immunological basis of silymarin effect, a milk thistle (Silybum
      marianum) against ethanol-induced oxidative damage.
AB  - Ethanol metabolism induces generation of excessive amount of reactive oxygen
      species (ROS) which results in immune dysfunction. We examined the efficacy of
      silymarin on ethanol-induced oxidative stress, immunomodulatory activity, and
      vascular function in mice blood. Effectiveness of silymarin was compared with
      potent antioxidant ascorbic acid. In the present study, 8- to 10-week-old male
      BALB/c mice (20-30 g) were divided into the four groups of six each. One group
      were fed with ethanol (1.6 g/kg body weight), while second group were fed with
      ethanol (1.6 g/kg body weight) and silybin (250 mg/kg body weight), and the third
      group were exposed to ethanol (250 mg/kg body weight) and ascorbic acid (250
      mg/kg body weight) per day for 12 weeks. The control group was fed with
      isocaloric glucose solution instead of ethanol. Ethanol exposure significantly
      increased thiobarbituric acid reactive substance (TBARS) and nitrite levels
      besides glutathione-S-transferase (GST) activity, and significantly decreased
      reduced glutathione (GSH) content and the activities of superoxide dismutase
      (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase
      (GPx) in whole blood hemolyzate, while silymarin treatment significantly
      normalized these altered parameters. Silymarin significantly prevented ethanol
      induced, elevated activities of interleukin (IL)-10, tumor necrosis factor (TNF)
      alpha, gamma interferon (IFN-gamma), vascular endothelial growth factor (VEGF)-A,
      and transforming growth factor (TGF)-beta1, as well as decreased IL-4 activity in
      mice blood. These results were comparable with the activity of ascorbic acid.

PMID- 22409311
TI  - Mnemonic strategy training improves memory for object location associations in
      both healthy elderly and patients with amnestic mild cognitive impairment: a
      randomized, single-blind study.
AB  - OBJECTIVE: To evaluate the efficacy of mnemonic strategy training versus a
      matched-exposure control condition and to examine the relationship between
      training-related gains, neuropsychological abilities, and medial temporal lobe
      volumetrics in patients with amnestic mild cognitive impairment (aMCI) and age
      matched healthy controls. METHOD: Twenty-three of 45 screened healthy controls
      and 29 of 42 screened patients with aMCI were randomized to mnemonic strategy or
      matched-exposure groups. Groups were run in parallel, with participants blind to
      the other intervention. All participants completed five sessions within 2 weeks.
      Memory testing for object-location associations (OLAs) was performed during
      sessions one and five and at a 1-month follow-up. During Sessions 2-4,
      participants received either mnemonic strategy training or a matched number of
      exposures with corrective feedback for a total of 45 OLAs. Structural magnetic
      resonance imaging was performed in most participants, and medial temporal lobe
      volumetrics were acquired. RESULTS: Twenty-one healthy controls and 28 patients
      with aMCI were included in data analysis. Mnemonic strategy training was
      significantly more beneficial than matched exposure immediately after training, p
      = .006, partial eta2 = .16, and at 1 month, p < .001, partial eta2 = .35,
      regardless of diagnostic group (healthy group or aMCI group). Although patients
      with aMCI demonstrated gains comparable to the healthy control groups, their
      overall performance generally remained reduced. Mnemonic strategy-related
      improvement was correlated positively with baseline memory and executive
      functioning and negatively with inferior lateral ventricle volume in patients
      with aMCI; no significant relationships were evident in matched-exposure
      patients. CONCLUSION: Mnemonic strategies effectively improve memory for specific
      content for at least 1 month in patients with aMCI.

PMID- 22409312
TI  - The effects of environmental conditions on persistence and inactivation of
      Brucella suis on building material surfaces.
AB  - AIMS: The purpose of this study was to evaluate the effects of environmental
      conditions and material type on persistence and inactivation of Brucella suis.
      METHODS AND RESULTS: Brucella suis (approx. 1 * 10(8) CFU) was spiked onto
      surfaces (glass, aluminium and wood) by liquid inoculation. Persistence was
      evaluated over 56 days at 22 +/- 2 degrees C, 40 +/- 15% r.h. and 5 +/- 3 degrees
      C, 30 +/- 15% r.h. In addition, three readily available decontaminants (pH
      adjusted bleach, 70% ethanol and 1% citric acid) were evaluated for their
      effectiveness at inactivating Br. suis on these materials. Decontaminations were
      conducted following 0 and 28 days exposure to the two conditions. Results
      indicated that Br. suis can persist on environmental surfaces for at least 56
      days. Persistence was highest at low temperature. Decontamination was most
      challenging on wood with all three decontaminants. CONCLUSIONS: Following a Br.
      suis contamination incident, passive decontamination (through attenuation) may
      not be feasible, as this organism can persist for months. In addition, the
      results suggest that some sporicidal decontaminants may be ineffective on
      materials such as wood, even for vegetative biological agents such as Br. suis.
      SIGNIFICANCE AND IMPACT OF STUDY: This study aids incident commanders and
      remediation experts to make informed decisions regarding decontamination after a
      biological contamination incident.

PMID- 22409313
TI  - The conformationally constrained N-methanocarba-dT analogue adopts an unexpected
      C4'-exo sugar pucker in the structure of a DNA hairpin.
AB  - Incorporation of a bicyclo[3.1.0]hexane scaffold into the nucleoside sugar was
      devised to lock the embedded cyclopentane ring in conformations that mimic the
      furanose North and South sugar puckers. To analyze the effects of North
      methanocarba-2'-deoxythymidine (N-MCdT) on the B-form DNA, we crystallized
      d(CGCGAA[mcTmcT]CGCG) with two N-MCdTs. Instead of a duplex, the 12mer forms a
      tetraloop hairpin, whereby loop N-MCdTs adopt the C4'-exo pucker (NE; P = 50
      degrees ). Thus, the bicyclic framework does not limit the pucker to the
      anticipated C2'-exo range (NNW; P = -18 degrees ).

PMID- 22409314
TI  - Generation, spectroscopy, and structure of cyanoformyl chloride and cyanoformyl
      bromide, XC(O)CN.
AB  - Cyanoformyl chloride and cyanoformyl bromide, XC(O)CN (X = Cl and Br), have been
      investigated in the gas phase by UV photoelectron and mid-infrared
      spectroscopies. The ground-state geometries of the neutral molecules have been
      obtained from quantum-chemical calculations at the B3LYP and CCSD(T) levels using
      the aug-cc-pVTZ basis set. The individual spectroscopies provide a detailed
      investigation into the vibrational and electronic character of the molecules and
      are supported by quantum-chemical calculations. The results are compared to data
      for structurally and chemically related molecules.

PMID- 22409315
TI  - The COPD pipeline XV.

PMID- 22409316
TI  - Treatment of Congenitally Missing Maxillary Lateral Incisors:  An
      Interdisciplinary Approach.
AB  - Abstract   Not needed-Clinical Letter.

PMID- 22409317
TI  - Syndrome of inappropriate antidiuretic hormone secretion associated with primary
      cutaneous anaplastic large cell lymphoma.

PMID- 22409318
TI  - Triclinic-cubic phase transition and negative expansion in the actinide IV (Th,
      U, Np, Pu) diphosphates.
AB  - The AnP(2)O(7) diphosphates (An = Th, U, Np, Pu) have been synthesized by various
      routes depending on the stability of the An(IV) cation and its suitability for
      the unusual octahedral environment. Synchrotron and X-ray diffraction, thermal
      analysis, Raman spectroscopy, and (31)P nuclear magnetic resonance reveal them as
      a new family of diphosphates which probably includes the recently studied
      CeP(2)O(7). Although they adopt at high temperature the same cubic archetypal
      cell as the other known MP(2)O(7) diphosphates, they differ by a very faint
      triclinic distortion at room temperature that results from an ordering of the
      P(2)O(7) units, as shown using high-resolution synchrotron diffraction for
      UP(2)O(7). The uncommon triclinic-cubic phase transition is first order, and its
      temperature is very sensitive to the ionic radius of An(IV). The conflicting
      effects which control the thermal variations of the P-O-P angle are responsible
      for a strong expansion of the cell followed by a contraction at higher
      temperature. This inversion of expansion occurs at a temperature significantly
      higher than the phase transition, at variance with the parent compounds with
      smaller M(IV) cations in which the two phenomena coincide. As shown by various
      approaches, the P-O(b)-P linkage remains bent in the cubic form.

PMID- 22409319
TI  - Distribution of the vanG-like gene cluster in  Clostridium difficile  clinical
      isolates.
AB  - Treatment of  Clostridium difficile  infections generally requires cessation of
      their causative antibiotic and subsequent administration of metronidazole or
      vancomycin. Intriguingly, the genome of C. difficile 630 contains a cryptic gene
      cluster homologous to the vanG-type operon of  Enterococcus faecalis  BM4518. We
      detected this cluster by PCR in 35 out of 41 clinical isolates, confirming its
      large prevalence in this species. The cluster was found to be located in a unique
      locus. Comparison of this locus with that of strains devoid of the vanG-like
      cluster indicated that acquisition of the gene cluster occurred in a perfect 19
      bp inverted repeat, in the absence of a detectable mobile structure.

PMID- 22409320
TI  - Evaluation of small molecule tuberculostats for targeting tuberculosis infections
      of the central nervous system.
AB  - Tuberculosis infection of the central nervous system is a serious and frequently
      fatal disease. Four drugs have been found to very efficiently inhibit the growth
      of Mycobacterium tuberculosis and are examined for molecular properties that
      enable penetration of the blood-brain barrier. Drugs 1, 2, and 3 are aromatic
      compounds having a single bromine atom in ortho, meta, and para-position,
      respectively, relative to the hydrazide group (-C(O)NHNH2). A paraposition for
      bromine enabled the strongest inhibition of Mycobacterium tuberculosis. Drug 4 is
      a hydrazide derivative of ciprofloxacin. All drugs showed molecular properties
      suitable for targeting tuberculosis infections of the central nervous system.
      Drugs 1, 2, 3, 4, and isoniazid showed zero violations of the Rule of 5 and
      potential capability for oral administration. Values of BB (Cbrain/Cblood)
      suggested that drugs 1, 2, and 3 will be able to penetrate the brain
      approximately three times greater than isoniazid. Similarly, the calculated value
      of BB for drug 4 is comparable to that of isoniazid. Calculated values of polar
      surface area for drugs 1, 2, 3, and isoniazid indicated a potential rate of
      intestinal absorption of greater than 75% of drug amount present. The intestinal
      absorption of drug 4 is predicted to be greater than 50% of total amount present.
      Drug concentrations necessary for achieving MIC50 for 1, 2, 3, 4, and isoniazid
      are determined to be 65.9 MUg/mL, 29.5 MUg/mL, 21.5 MUg/mL, 36.4 MUg/mL, and 16.7
      MUg/mL, respectively. The position of the bromine atom within drugs 1, 2, and 3
      appears to substantially influence the effectiveness of growth inhibition. These
      compounds show substantial potential for targeting tuberculosis infections within
      the central nervous system.

PMID- 22409321
TI  - In vitro antimicrobial activity of miconazole and polymyxin B against canine
      meticillin-resistant Staphylococcus aureus and meticillin-resistant
      Staphylococcus pseudintermedius isolates.
AB  - BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) and meticillin
      resistant Staphylococcus pseudintermedius (MRSP) infections are increasingly
      reported in dogs, and these bacteria may be isolated from ear infections.
      HYPOTHESIS/OBJECTIVES: The main aim of the present study was to investigate the
      in vitro antimicrobial activity of miconazole, polymyxin B and a combination of
      both against 24 canine MRSA and 50 canine MRSP isolates. The minimal inhibitory
      concentration (MIC) values of 12 other antimicrobial agents were also determined.
      METHODS: All MIC values were determined according to a broth microdilution assay.
      RESULTS: Acquired resistance was found to all tested agents, except for
      linezolid, miconazole and polymyxin B. The MIC values for miconazole and
      polymyxin B against MRSA were in the range of 4-8 and 8-64 MUg/mL, respectively,
      while the MIC values for miconazole and polymyxin B against MRSP were in the
      range of 1-2 and 0.25-4 MUg/mL, respectively. Using a combination of miconazole
      and polymyxin B, there was no evidence for enhanced in vitro activity of the
      combination (i.e. synergy) of both products. Nevertheless, MIC(90) values of the
      combination of these antimicrobial agents and of a commercial product containing
      both agents were at least 1000 times lower than the concentration present in the
      commercial product. CONCLUSIONS AND CLINICAL IMPORTANCE: These results indicate
      that the topical use of a combination of miconazole and polymyxin B in a 43.5:1
      ratio may have potential for the treatment of MRSA-mediated and MRSP-associated
      otitis externa in dogs.

PMID- 22409322
TI  - Odontostomatologic involvement in juvenile localised scleroderma of the face.
AB  - AIM: Localised scleroderma of the face (LSF) can lead to significant aesthetical
      and functional abnormalities. Despite their quite frequent clinical observation,
      the odontostomatologic complications are not thoroughly described. Aim of the
      study was to describe the clinical features of the most frequent
      odontostomatologic abnormalities of LSF and to propose clinical and radiologic
      criteria for the assessment and follow-up of these complications. METHODS:   We
      performed a cross-sectional, multicenter study involving a multidisciplinary team
      formed by paediatric rheumatologists, orthodontists and radiologists. Patients
      with a diagnosis of LSF underwent a comprehensive rheumatologic evaluation,
      dental examination, conventional radiology (orthopantomography, teleradiography)
      and cone beam computed tomography. RESULTS: 16 patients, nine F, seven M, aged
      6.5-21.9 years, were investigated. The mean disease duration was 7.7 years, 62.5%
      had extracutaneous complications. All patients reported at least one
      odontostomatologic complication. The main alterations were: malocclusion (94%),
      overgrowth tendency of the anterior lower third of the face (82%), gnatologic
      alterations (69%), dental anomalies (63%), skeletal asymmetry (56%), bone
      involvement (50%) and temporomandibular joint involvement (19%). CONCLUSIONS: We
      found a high incidence of odontostomatologic abnormalities in LSF. Cone beam
      computed tomography represents a new feasible technique to evaluate and monitor
      soft and hard tissue changes in LSF. The observed findings highlight the
      importance of a multidisciplinary and standardised management of this challenging
      and rare condition.

PMID- 22409323
TI  - Spectral clustering in peptidomics studies allows homology searching and
      modification profiling: HomClus, a versatile tool.
AB  - Many genomes of nonmodel organisms are yet to be annotated. Peptidomics research
      on those organisms therefore cannot adopt the commonly used database-driven
      identification strategy, leaving the more difficult de novo sequencing approach
      as the only alternative. The reported tool uses the growing resources of publicly
      or in-house available fragmentation spectra and sequences of (model) organisms to
      elucidate the identity of peptides of experimental spectra of nonannotated
      species. Clustering algorithms are implemented to infer the identity of unknown
      peak lists based on their publicly or in-house available counterparts. The
      reported tool, which we call the HomClus-tool, can cope with post-translational
      modifications and amino acid substitutions. We applied this tool on two locusts
      (Schistocerca gregaria and Locusta migratoria) LC-MALDI-TOF/TOF datasets.
      Compared to a Mascot database search (using the available UniProt-KB proteins of
      these species), we were able to double the amount of peptide identifications for
      both spectral sets. Known bioactive peptides from Drosophila melanogaster (i.e.,
      fragmentations spectra generated in silico thereof) were used as a starting point
      for clustering, trying to reveal their experimental homologues' counterparts.

PMID- 22409325
TI  - Peracetylated (-)-epigallocatechin-3-gallate (AcEGCG) potently suppresses dextran
      sulfate sodium-induced colitis and colon tumorigenesis in mice.
AB  - Previous studies reported that peracetylated (-)-epigallocatechin-3-gallate
      (AcEGCG) has antiproliferative and anti-inflammatory activities. Here, we
      evaluated the chemopreventive effects and underlying molecular mechanisms of
      dietary administration of AcEGCG and EGCG in dextran sulfate sodium (DSS)-induced
      colitis in mice. The mice were fed a diet supplemented with either AcEGCG or EGCG
      prior to DSS induction. Our results indicated that AcEGCG administration was more
      effective than EGCG in preventing the shortening of colon length and the
      formation of aberrant crypt foci (ACF) and lymphoid nodules (LN) in mouse colon
      stimulated by DSS. Our study observes that AcEGCG treatment inhibited histone 3
      lysine 9 (H3K9) acetylation but did not affect histone acetyltransferase (HAT)
      activity and acetyl- CREB-binding protein (CBP)/p300 levels. In addition,
      pretreatment with AcEGCG decreased the proinflammatory mediator levels by down
      regulating of PI3K/Akt/NFkappaB phosphorylation and p65 acetylation. We also
      found that treatment with AcEGCG increased heme oxygenase-1(HO-1) expression via
      activation of extracellular signal-regulated protein kinase (ERK)1/2 signaling
      and acetylation of NF-E2-related factor 2 (Nrf2), thereby abating DSS-induced
      colitis. Moreover, dietary feeding with AcEGCG markedly reduced colitis-driven
      colon cancer in mice. Taken together, these results demonstrated for the first
      time the in vivo chemopreventive efficacy and molecular mechanisms of dietary
      AcEGCG against inflammatory bowel disease (IBD) and potentially colon cancer
      associated with colitis. These findings provide insight into the biological
      actions of AcEGCG and might establish a molecular basis for the development of
      new cancer chemopreventive agents.

PMID- 22409328
TI  - Portal hypertension after combined liver and intestinal transplantation, a
      diagnostic and therapeutic challenge?
AB  - A widely accepted technique to transplant the liver-bowel bloc is first to
      perform a piggyback anastomosis of the donor suprahepatic vena cava to the
      recipient vena cava; second to restore the arterial blood supply through an
      aortic interposition graft; and third to ensure venous drainage of the native
      foregut. The venous drainage of the native foregut can be restored through an end
      to-end portocaval anastomosis between the donor infrahepatic vena cava and the
      recipient portal vein. Stenosis of this anastomosis can lead to portal
      hypertension presenting with upper GI congestion, bleeding, and hypersplenism. We
      report the successful treatment of this complication using an e-PTFE-covered
      stent inserted following balloon angioplasty.

PMID- 22409329
TI  - The identification of two unusual types of homemade ammunition.
AB  - Illegal homemade ammunition is commonly used by criminals to commit crimes in
      Taiwan. Two unusual types of homemade ammunition that most closely resembling
      genuine ammunition are studied here. Their genuine counterparts are studied as
      the control samples for the purpose of comparison. Unfired ammunition is
      disassembled, and the morphological, dimensional, and compositional features of
      the bullet and cartridge case are examined. Statistical tests are employed to
      distinguish the dimensional differences between homemade and genuine ammunitions.
      Manufacturing marks on head stamps of the cartridge case are carefully examined.
      Compositional features of propellant powders, primer mixtures, and gunshot
      residues are also analyzed. The results reveal that the morphological,
      dimensional, and compositional features of major parts of the ammunition can be
      employed to differentiate homemade cartridges from genuine ones. Among these
      features, tool marks on the head stamps left by the bunter can be used to trace
      the origin of ammunition.

PMID- 22409330
TI  - Atomic force microscopy imaging reveals the domain structure of polycystin-1.
AB  - Mutation of polycystin-1 (PC1) is the major cause of autosomal dominant
      polycystic kidney disease. PC1 has a predicted molecular mass of ~460 kDa
      comprising a long multidomain extracellular N-terminal region, 11 transmembrane
      regions, and a short C-terminal region. Because of its size, PC1 has proven
      difficult to handle biochemically, and structural information is consequently
      sparse. Here we have isolated wild-type PC1, and several mutants, from
      transfected cells by immunoaffinity chromatography and visualized individual
      molecules using atomic force microscopy (AFM) imaging. Full-length PC1 appeared
      as two unequally sized blobs connected by a 35 nm string. The relative sizes of
      the two blobs suggested that the smaller one represents the N-terminus, including
      the leucine-rich repeats, the first polycystic kidney disease (PKD) domain, and
      the C-type lectin motif, while the larger one is the C-terminus, including the
      receptor for egg jelly (REJ) domain, all transmembrane domains, and the
      cytoplasmic tail. The intervening string would then consist of a series of tandem
      PKD domains. The structures of the various PC1 mutants were all consistent with
      this model. Our results represent the first direct visualization of the structure
      of PC1, and reveal the architecture of the protein, with intriguing implications
      for its function.

PMID- 22409331
TI  - Advantages of self-tailored mesh for vaginal prolapse.

PMID- 22409332
TI  - A highly elastic, capacitive strain gauge based on percolating nanotube networks.
AB  - We present a highly elastic strain gauge based on capacitive sensing of parallel,
      carbon nanotube-based percolation electrodes separated by a dielectric elastomer.
      The fabrication, relying on vacuum filtration of single-walled carbon nanotubes
      and hydrophobic patterning of silicone, is both rapid and inexpensive. We
      demonstrate reliable, linear performance over thousands of cycles at up to 100%
      strain with less than 3% variability and the highest reported gauge factor for a
      device of this class (0.99). We further demonstrate use of this sensor in a
      robotics context to transduce joint angles.

PMID- 22409333
TI  - Risk-related issues.

PMID- 22409334
TI  - On frequency.

PMID- 22409337
TI  - The affect heuristic, correspondence analysis, and understanding LULUs.

PMID- 22409338
TI  - The content and not only the valence of spontaneous associations should be
      analyzed.

PMID- 22409340
TI  - Examining frontotemporal connectivity and rTMS in healthy controls: implications
      for auditory hallucinations in schizophrenia.
AB  - OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has been shown to
      have clinically beneficial effects in altering the perception of auditory
      hallucinations (AH) in patients with schizophrenia. However, the mode of action
      is not clear. Recent neuroimaging findings indicate that rTMS has the potential
      to induce not only local effects but also changes in remote, functionally
      connected brain regions. Frontotemporal dysconnectivity has been proposed as a
      mechanism leading to psychotic symptoms in schizophrenia. The current study
      examines functional connectivity between temporal and frontal brain regions after
      rTMS and the implications for AH in schizophrenia. METHOD: A connectivity
      analysis was conducted on the fMRI data of 11 healthy controls receiving rTMS,
      compared with 11 matched subjects receiving sham TMS, to the temporoparietal
      junction, before engaging in a task associated with robust frontotemporal
      activation. RESULTS: Compared to the control group, the rTMS group showed an
      altered frontotemporal connectivity with stronger connectivity between the right
      temporoparietal cortex and the dorsolateral prefrontal cortex and the angular
      gyrus. CONCLUSION: This finding provides preliminary evidence for the hypothesis
      that normalizing the functional connectivity between the temporoparietal and
      frontal brain regions may underlie the therapeutic effect of rTMS on AH in
      schizophrenia.

PMID- 22409339
TI  - Changes in response bias with different study-test delays: evidence from young
      adults, older adults, and patients with Alzheimer's disease.
AB  - OBJECTIVE: Along with impaired discrimination, patients with Alzheimer's disease
      (AD) often show an abnormally liberal response bias (greater tendency to respond
      "old"). Previously we matched discrimination by varying study-test list length
      and found that participants' usual bias is maintained, such that patients with AD
      were more liberal than healthy controls. However, this pattern could be a result
      of the way in which discrimination was matched. In this experiment, we examined
      whether matching discrimination with the use of a delay would lead to a liberal
      response bias in healthy younger and older adults as it might lead to the use of
      more similar memorial processing to the patients with AD. METHOD: Younger adults,
      older adults, and patients with AD were run in 2 study-test sessions, with study
      and recognition test separated by either a 1-min or 1-day delay. RESULTS: With
      the 1-min delay, both younger adults and healthy older adults showed a
      conservative response bias, while patients with AD showed a liberal response
      bias. When discrimination was matched between patients with AD and controls by
      the use of a delay, response bias was also matched, with all participants showing
      a more liberal response bias. CONCLUSIONS: The current study suggests that how
      discrimination is matched between patients with AD and controls matters greatly.
      Potentially, this liberal bias is a result of healthy younger and older adults
      relying primarily on familiarity at the longer delay, thus using more similar
      memorial processes to patients with AD who are dependent on familiarity at any
      delay.

PMID- 22409341
TI  - A systematic review of the effectiveness of videoconference-based tele-education
      for medical and nursing education.
AB  - BACKGROUND: Rural nurses and doctors typically have little opportunity to further
      their education and training. Studies have shown high participant satisfaction
      with the use of educational technology, such as videoconferencing, for education.
      A review of effectiveness of videoconference-based tele-education for medical and
      nursing education was conducted. AIMS: The aims of this study were to: (1)
      systematically review the literature and critique the research methods on studies
      addressing the review question: "How effective is videoconference-based education
      for the education of doctors and nurses?" (2) summarize the existing evidence on
      the effectiveness of videoconference education for medical and nursing staff; and
      (3) apply the findings to South Africa and other countries across the globe.
      METHODS: Research citations from 1990 to 2011 from cumulative index of nursing
      and allied health literature, Medline, Pubmed, PsycInfo, EBSCOhost, SABINET,
      Cochrane Database of Systematic Reviews, the Cochrane Controlled Trial Registry,
      Database of Abstracts of Reviews of Effectiveness, unpublished abstracts through
      NEXUS and Internet search engines (Google/Google scholar) were searched. Review
      methods included searching, sifting, abstraction, and quality assessment of
      relevant studies by two reviewers. Studies were evaluated for sample, design,
      intervention, threats to validity, and outcomes. No meta-analysis was conducted
      as the studies provided heterogeneous outcome data. RESULTS: Five studies were
      reviewed. Videoconference and face-to-face education is at least equivalent and
      one study reported an increase in knowledge and knowledge integration.
      RECOMMENDATIONS: Despite the methodological limitations and heterogeneity of the
      reviewed studies, there appears to be sufficient evidence of effectiveness to
      provide a rigorous Grade B evidence-based recommendation of moderate support.
      CONCLUSIONS: The use of videoconferencing for nursing and medical education
      should be encouraged along with guidelines for the use of videoconferencing. The
      paucity of studies and the lack of empirical precision in evaluating
      effectiveness of these interventions necessitate future rigorously designed
      experimental studies.

PMID- 22409343
TI  - Mechanism of JNK signal regulation by placental HSP70 and HSP90 in endothelial
      cell during preeclampsia.
AB  - CONTEXT: Preeclampsia is a placenta related disorder of during pregnancy
      resulting in pre- and post-partum complications of the both mother and fetus. It
      is associated with improper trophoblast invasion and maternal endothelial cell
      dysfunction leading to a placental dysregulation resulting in premature delivery.
      OBJECTIVE: Aim of the present study is to elucidate of the protective role of
      chaperones (HSP70 and 90) in preeclampsia and to test whether it is associated
      with oxidative stress level in placental tissue. MATERIALS AND METHODS:
      Endothelial cell from normotensive and preeclamptic placenta were analyzed for
      variation in viability and expression of signaling molecules. RESULTS: A
      significant decrease in viability of endothelial cell (p < 0.05) was noted in
      preeclamptic samples when compared to normotensive samples. The results indicate
      that there were increases in HSP70 and HSP90 (p <0.01), HSF1 (p <0.01), NF-kappaB
      (p <0.05), JNK1 (p <0.05), JNK2 (p> 0.05) and Bcl2 (p <0.05). DISCUSSION: The
      significant change in the viability of endothelial cell has not predominantly
      affected the live fetal delivery during preeclampsia. This is governed by
      alterations in expression of nuclear transcription factors like HSF1, NF-kappaB
      and signaling molecules like JNK1/2 and Bcl2 in preeclamptic endothelial cell.
      CONCLUSION: This HSP mediated signal changes may contribute to live fetal
      delivery in spite of existing endothelial cell complication during preeclampsia.

PMID- 22409345
TI  - Gas-phase oxidation reactions of Ta2+: synthesis and properties of TaO(2+) and
      TaO2(2+).
AB  - Gas-phase reactions of Ta(2+) and TaO(2+) with oxidants, including
      thermodynamically facile O-atom donor N(2)O and ineffective donor CO, as well as
      intermediate donors C(2)H(4)O (ethylene oxide), H(2)O, O(2), CO(2), NO, and
      CH(2)O, were studied by Fourier transform ion cyclotron resonance mass
      spectrometry. All oxidants reacted with Ta(2+) by electron transfer yielding
      Ta(+), in accord with the high second ionization energy of Ta (ca. 16 eV).
      TaO(2+) was also produced with N(2)O, H(2)O, O(2), and CO(2), oxidants with
      ionization energies above 12 eV; CO reacted only by electron transfer. The
      following charge separation products were also observed: TaN(+) and TaO(+) with
      N(2)O; and TaO(+) with O(2), CO(2), and CH(2)O. TaOH(2+), formed with H(2)O,
      reacted with a second H(2)O by proton transfer. TaO(2+) abstracted an electron
      from N(2)O, H(2)O, O(2), CO(2), and CO. Oxidation of TaO(2+) by N(2)O was also
      observed to produce TaO(2)(2+); on the basis of density functional theory (DFT)
      results, this species is a dioxide, {O-Ta-O}(2+). TaO(2)(2+) reacted by electron
      transfer with N(2)O, CO(2), and CO to give TaO(2)(+). Additionally, it was found
      that TaO(2)(2+) oxidizes CO to CO(2) and that it acts as a catalyst in the
      oxidation of CO by N(2)O. TaO(2)(2+) also activates H(2) to form TaO(2)H(2+). On
      the basis of the rates of electron transfer from N(2)O, CO(2), and CO to Ta(2+),
      TaO(2+), and TaO(2)(2+), the following estimates were made for the second
      ionization energies of Ta, TaO, and TaO(2): IE[Ta(+)] = 15.8 +/- 0.3 eV,
      IE[TaO(+)] = 16.0 +/- 0.5 eV, and IE[TaO(2)(+)] = 16.9 +/- 0.4 eV. These IEs,
      together with recently reported bond dissociation energies, D[Ta(+)-O] and
      D[OTa(+)-O], result in the following bond energies: D[Ta(2+)-O] = 657 +/- 58 kJ
      mol(-1) and D[OTa(2+)-O] = 500 +/- 63 kJ mol(-1), the first of which is in good
      agreement with the value obtained by DFT.

PMID- 22409342
TI  - Protein kinases: emerging therapeutic targets in chronic lymphocytic leukemia.
AB  - INTRODUCTION: Although protein kinases are primary targets for inhibition in
      hematological malignancies, until recently their contribution to chronic
      lymphocytic leukemia (CLL) was poorly understood. Insights into B-cell receptor
      signaling and its role in regulating key cellular functions have shed light on
      candidate protein kinases that are aberrantly activated in CLL. In this regard,
      protein kinases are now considered as potential drug targets in CLL. AREA
      COVERED: This review has covered signaling pathways and associated protein
      kinases in CLL and the kinase inhibitors currently available in preclinical and
      clinical investigations. Individual protein kinases that are abnormally active in
      CLL and the functional consequences of their inhibition are discussed. EXPERT
      OPINION: A growing body of evidence suggests that protein kinases are druggable
      targets for patients with CLL. The emergence of novel and bio-available kinase
      inhibitors and their promising clinical activity in CLL underscore the oncogenic
      role of kinases in leukemogenesis. Further investigations directed towards their
      role as single agents or in combinations may provide insight into understanding
      the substantial role of kinase-mediated signal transduction pathways and their
      inhibition in B- CLL.

PMID- 22409346
TI  - Renal iron load in sickle cell disease is influenced by severity of haemolysis.
AB  - Spin density projection-assisted R2-magnetic resonance imaging (R2-MRI;
      FerriScan((r))) scans from 40 chelation-naive sickle cell patients were used to
      assess renal iron load by measuring renal R2 (R-R2). Clinical data were collected
      retrospectively for the 2-year period preceding the scan. R-R2 showed no
      significant correlation with transfusional iron load (assessed by liver iron
      concentration), but correlated significantly with serum bilirubin (R = 0.61, P <
      0.0001) and lactate dehydrogenase (R = 0.58, P < 0.0001). Mean (+/-standard
      deviation) R-R2 was higher (P = 0.02) in patients with renal hyperfiltration
      (29.8 +/- 10.3/s) than those without (23.11 +/- 6.6/s). Five patients had
      significantly lower signal intensity in the renal cortex, as compared to the
      medulla. These patients had a significantly higher (P < 0.0001) mean R-R2 than
      those showing no cortico-medullary difference. We postulate that the increased R
      R2 is associated with haemolysis rather than transfusional iron load in sickle
      cell disease.

PMID- 22409347
TI  - Alternatives to conventional antimicrobial drugs: a review of future prospects.
AB  - BACKGROUND: Growing antimicrobial resistance poses the threat that before long no
      suitable drugs will be available for treatment of common infections. This review
      examines promising new strategies for treatment and control of microbial
      diseases, with an emphasis on staphylococcal infection. NEW DRUGS AND TARGETS:
      Advances in microbial genomics have provided tools identifying many new targets
      for antimicrobial drugs. Of particular interest amongst these are inhibition of
      microbial efflux pump activity, interruption or diversion of riboswitches
      controlling bacterial metabolism, and metagenomics, which allows analysis of
      genes from unculturable organisms. BIOLOGICAL APPROACHES: Advances are also being
      made in biological systems for disease control, with the exploitation of
      antimicrobial peptides to attack micro-organisms and modulate immune responses,
      and the use of bacteriophages or their lysins to eliminate bacteria. There are
      new approaches in the development and targeting of vaccines and immunoglobulin
      preparations based on advanced knowledge of microbial physiology and
      immunoregulation. WORKING WITH THE BIOME: With increasing recognition of the
      value of the normal microbiota in modulating immunity and the establishment of
      pathogens, there is growing interest in understanding the mammalian microbiome.
      Strategies are being developed to promote or maintain the normal microbiota,
      including the use of probiotics, and there is re-evaluation of the potential of
      bacterial interference. LOOKING AHEAD: Whilst these approaches are likely to
      generate new methods of disease control, few will yield usable products within
      the near future. There will be a continuing need for careful use of existing
      drugs based on firm diagnosis, rigorous hygiene and prudent antimicrobial
      stewardship.

PMID- 22409349
TI  - Role of maize hybrids and their chemical composition in Fusarium infection and
      fumonisin production.
AB  - This study was designed to investigate the role of hybrids in maize Fusarium
      section Liseola interaction and fumonisin production, with particular emphasis on
      the occurrence and accumulation of hidden fumonisins in maize (masking
      phenomenon). In this 2 year study, naturally infected field crops were chosen
      with 10 maize hybrids, six of them grown in both years. Maize samples collected
      in 2010 showed a higher incidence of fungal infection as well as higher fumonisin
      contamination than those obtained in 2009 but a very similar incidence of F.
      section Liseola. Fumonisin masking was confirmed in raw maize, with a lower
      amount of hidden forms as compared to free fumonisins detected in the year with
      higher contamination. The chemical composition of the different hybrids was
      determined and correlated with the contamination data: the results obtained
      highlight the main role of fatty acids, with a higher fumonisin contamination in
      hybrids showing a higher linoleic acid content and a higher masking action in
      hybrids with higher oleic to linoleic ratio. These results represent a good basis
      to explain maize hybrid susceptibility to F. section Liseola infection, fumonisin
      contamination, and masking not related to a specific commercial hybrid but
      extendable to all hybrids.

PMID- 22409348
TI  - Multiple binding sites for fatty acids on the potassium channel KcsA.
AB  - Interactions of fatty acids with the potassium channel KcsA were studied using
      Trp fluorescence quenching and electron paramagnetic resonance (EPR) techniques.
      The brominated analogue of oleic acid was shown to bind to annular sites on KcsA
      and to the nonannular sites at each protein-protein interface in the
      homotetrameric structure with binding constants relative to
      dioleoylphosphatidylcholine of 0.67 +/- 0.04 and 0.87 +/- 0.08, respectively.
      Mutation of the two Arg residues close to the nonannular binding sites had no
      effect on fatty acid binding. EPR studies with a spin-labeled analogue of stearic
      acid detected a high-affinity binding site for the fatty acid with strong
      immobilization. Fluorescence quenching studies with the spin-labeled analogue
      showed that the binding site detected in the EPR experiments could not be one of
      the annular or nonannular binding sites. Instead, it is proposed that the EPR
      studies detect binding to the central hydrophobic cavity of the channel, with a
      binding constant in the range of ~0.1-1 MUM.

PMID- 22409350
TI  - Facile synthesis of BaTiO3 nanotubes and their microwave absorption properties.
AB  - Uniform BaTiO(3) nanotubes were synthesized via a simple wet chemical route at
      low temperature (50  degrees C). The as-synthesized BaTiO(3) nanotubes were
      characterized using powder X-ray diffraction, field-emission scanning electron
      microscopy, transmission electron microscopy, Raman spectroscopy, and X-ray
      photoelectron spectroscopy. The results show that the BaTiO(3) nanotubes formed a
      cubic phase with an average diameter of ~10 nm and wall thickness of 3 nm at room
      temperature. The composition of the mixed solvent (ethanol and deionized water)
      was a key factor in the formation of these nanotubes; we discuss possible
      synthetic mechanisms. The microwave absorption properties of the BaTiO(3)
      nanotubes were studied at microwave frequencies between 0.5 and 15 GHz. The
      minimum reflection loss of the BaTiO(3) nanotubes/paraffin wax composite
      (BaTiO(3) nanotubes weight fraction = 70%) reached 21.8 dB (~99.99% absorption)
      at 15 GHz, and the frequency bandwidth less than -10 dB is from 13.3 to 15 GHz.
      The excellent absorption property of BaTiO(3) nanotubes at high frequency
      indicates that these nanotubes could be promising microwave-absorbing materials.

PMID- 22409351
TI  - Divalent lanthanide complexes supported by the bridged bis(amidinates) L
      Me3SiN(Ph)CN(CH2)3NC(Ph)NSiMe3]: synthesis, molecular structures and one-electron
      transfer reactions.
AB  - Metathesis reactions of YbI(2) with Li(2)L (L =
      Me(3)SiN(Ph)CN(CH(2))(3)NC(Ph)NSiMe(3)) in THF at a molar ratio of 1:1 and 1:2
      both afforded the Yb(II) iodide complex [{YbI(DME)(2)}(2)(MU(2)-L)] (1), which
      was structurally characterized to be a dinuclear Yb(II) complex with a bridged L
      ligand. Treatment of EuI(2) with Li(2)L did not afford the analogous
      [{EuI(DME)(2)}(2)(MU(2)-L)], or another isolable Eu(II) complex, but the
      hexanuclear heterobimetallic cluster [{Li(DME)(3)}(+)](2)[{(EuI)(2)(MU(2)
      I)(2)(MU(3)-L)(2)(Li)(4)}(MU(6)-O)](2-) (2) was isolated as a byproduct in a
      trace yield. The rational synthesis of cluster 2 could be realized by the
      reaction of EuI(2) with Li(2)L and H(2)O in a molar ratio of 1:1.5:0.5. The
      reduction reaction of LLnCl(THF)(2) (Ln = Yb and Eu) with Na/K alloy in THF gave
      the corresponding Ln(II) complexes [Yb(3)(MU(2)-L)(3)] (3) and [Eu(MU(2)
      L)(THF)](2) (4) in good yields. An X-ray crystal structure analysis revealed that
      each L in complex 3 might adopt a chelating ligand bonding to one Yb atom and
      each Yb atom coordinates to an additional amidinate group of the other L and acts
      as a bridging link to assemble a macrocyclic structure. Complex 4 is a dimer in
      which the two monomers [Eu(MU(2)-L)(THF)] are connected by two MU(2)-amidinate
      groups from the two L ligands. Complex 3 reacted with CyN?C?NCy and
      diazabutadienes [2,6-(i)Pr(2)C(6)H(3)N?CRCR?NC(6)H(3)(i)Pr(2)-2,6] (R?H, CH(3))
      (DAD) as a one-electron reducing agent to afford the corresponding Yb(III)
      derivatives: the complex with an oxalamidinate ligand
      [LYb{(NCy)(2)CC(NCy)(2)}YbL] (5) and the complexes containing a diazabutadiene
      radical anion [LYb((i)Pr(2)C(6)H(3)NCRCRNC(6)H(3)(i)Pr(2))] (R = H (6), R = CH(3)
      (7)). Complexes 5-7 were confirmed by an X-ray structure determination.

PMID- 22409353
TI  - Radiographic comparison of a fractured clavicle exhibiting a pseudo-arthrosis.
AB  - Bone remodeling is a natural process that is potentially problematic for
      radiographic comparisons because it can occur after antemortem (AM) imaging, thus
      interfering with the comparability of AM and postmortem (PM) radiographs from the
      same individual. While the effects of age-related remodeling have been studied,
      limited attention has been given to trauma-related remodeling with respect to
      radiographic comparisons. This report adds to the latter topic by presenting a
      case of AM clavicle fracture that developed into a pseudo-arthrosis over a 12
      month period prior to the individual's death. Even though remodeling was
      discernable along the fracture margins, adjacent skeletal features on the PM
      radiograph remained unaltered and constituted compelling evidence for the
      identification. This case illustrates the potential of using both normal and
      pathological anatomy concurrently to maximize the surety of findings from
      radiographic comparisons.

PMID- 22409352
TI  - Proteomic profiling of germ cell cancer cells treated with aaptamine, a marine
      alkaloid with antiproliferative activity.
AB  - Aaptamine is a marine compound isolated from the sponge Aaptos aaptos showing
      antiproliferative properties via an undefined mode of action. We analyzed the
      effects of aaptamine treatment on the proliferation and protein expression of the
      pluripotent human embryonal carcinoma cell line NT2. Effects on proliferation,
      cell cycle distribution, and induction of apoptosis were analyzed. At lower
      concentrations, including the IC50 of 50 MUM, aaptamine treatment resulted in a
      G2/M phase cell cycle arrest, whereas at higher concentrations, induction of
      apoptosis was seen. Differentially expressed proteins were assessed by 2D-PAGE
      and mass spectrometry, followed by verification and analysis of protein
      modifications of the most significantly up- and down-regulated proteins.
      Aaptamine treatment at the IC50 for 48 h resulted in alteration of 10 proteins,
      of which five each showed up- and down-regulation. Changes in the 2D map were
      frequently noticed as a result of post-transcriptional modifications, e.g., of
      the hypusine modification of the eukaryotic initiation factor 5A (eIF5A).
      Observed alterations such as increased expression of CRABP2 and hypusination of
      eIF5A have previously been identified during differentiation of pluripotent
      cells. For the first time, we describe changes in protein expression caused by
      aaptamine, providing valuable information regarding the mode of action of this
      compound.

PMID- 22409354
TI  - Combination laser-assisted liposuction and minimally invasive skin tightening
      with temperature feedback for treatment of the submentum and neck.
AB  - BACKGROUND: There is need for better nonsurgical treatment of excessive neck fat
      and skin laxity. OBJECTIVE: To assess combination laser-assisted liposuction
      (LAL) and minimally invasive skin tightening (MIST) of the submentum and neck
      under direct temperature control. DESIGN: Randomized, prospective, three-arm
      study of single LAL-MIST treatment comparing 1,064, 1,319 nm, and blended 1,064
      and 1,319 nm. METHODS: Twelve subjects were randomized to three arms. LAL was
      fiber administered into the adipose layer, followed by aspiration. MIST was laser
      fiber administered into the subdermal plane. Multiple passes were administered
      until uniform 45-48 degrees C was attained in the targeted plane. Energy delivery
      totalled 5,000-7,000 J. Subjects were photographed at baseline and 1, 2, 3, 4, 5,
      and 6 months after treatment and assessed using a 4-point quantitative laxity
      grading scale and fat aspirate quantitation. RESULTS: Mean +/- standard deviation
      baseline, follow-up, and difference in laxity grades and percentage improvement
      over baseline for the three study arms and total were 3.19 +/- 0.38%, 1.88 +/-
      0.85%, 1.31 +/- 0.55%, and 43.8 +/- 18.5%, respectively, for 1,064 nm; 3.75 +/-
      0.29%, 2.38 +/- 0.25%, 1.38 +/- 0.25%, and 36.6 +/- 5.9%, respectively, for 1,319
      nm; 3.38 +/- 0.48%, 2.13 +/- 0.63%, 1.25 +/- 0.29%, and 39.3 +/- 12.9%,
      respectively, for 1,064/1,319 nm; and 3.44 +/- 0.43%, 2.13 +/- 0.61%, 1.31 +/-
      0.36%, and 39.4 +/- 12.1%, respectively, total. Mean fat aspirate volumes were
      6.13 +/- 3.28 mL for 1,064 nm, 8.25 +/- 2.50 mL for 1,319 nm, and 6.50 +/- 5.74
      mL for 1,064/1,319 nm. Clinical improvement was consistent across all subjects;
      all before-and-after photographs are presented (save a recognizable subject for
      privacy). No blistering, scarring, or dyspigmentation was observed. CONCLUSION:
      Combination temperature-controlled LAL-MIST treats excess fat and skin laxity of
      the submentum and neck with excellent safety and efficacy.

PMID- 22409355
TI  - Broad diversity of conjugative plasmids in integron-carrying bacteria from
      wastewater environments.
AB  - In this study we assessed the occurrence, diversity and conjugative potential of
      plasmids in integron-carrying Aeromonas and Enterobacteriaceae from wastewaters.
      Sixty-six strains were included as donors in mating assays using rifampicin
      resistant Escherichia coli and Pseudomonas putida recipient strains. The
      diversity of plasmids from donors and transconjugants (resistant to tetracycline
      or streptomycin) was evaluated by restriction analysis and replicon typing
      targeting 19 incompatibility groups. Restriction patterns revealed a diverse
      plasmid pool present in these strains. Plasmids were assigned to FrepB (Aeromonas
      salmonicida, Aeromonas veronii, Aeromonas sp., E. coli, Enterobacter sp.), FIC
      (A. salmonicida, Aeromonas sp.), FIA (Shigella sp.), I1 (A. veronii, Aeromonas
      sp., E. coli), HI1 (E. coli) and U (Aeromonas media) replicons. Nevertheless, 50%
      of the plasmids could not be assigned to any replicon type. Among integron
      positive transconjugants, FrepB, I1 and HI1 replicons were detected. Results
      showed that wastewaters enclose a rich plasmid pool associated with integron
      carrying bacteria, capable of conjugating to different bacterial hosts. Moreover,
      replicons detected in this study in Aeromonas strains expand our current
      knowledge of plasmid diversity in this genus.

PMID- 22409356
TI  - D90A-SOD1 ALS mimicking monoclonal gammopathy-associated ALS.

PMID- 22409357
TI  - Gonadectomy and dehydroepiandrosterone (DHEA) do not modulate disease progression
      in the G93A mutant SOD1 rat model of amyotrophic lateral sclerosis.
AB  - Epidemiological studies have shown a higher incidence of amyotrophic lateral
      sclerosis (ALS) in men than women. Interestingly, there are clear gender
      differences in disease onset and progression in rodent models of familial ALS
      overexpressing mutated human superoxide dismutase-1 (SOD1-G93A). In the present
      study we sought to determine whether the alterations of serum steroid levels by
      gonadectomy or chronic treatment of neuroprotective neurosteroids can modulate
      disease onset and progression in a rat model of ALS (SOD1-G93A transgenic rats).
      Presymptomatic SOD1-G93A rats were gonadectomized or treated with a neurosteroid
      dehydroepiandrosterone (DHEA) using silastic tubing implants. Disease onset and
      progression of the animals were determined by the routine analyses of locomotor
      testing using the Basso-Beattie-Bresnahan (BBB) score. Although sexual dimorphism
      was observed in intact and gonadectomized SOD1-G93A rats, there was no
      significant effect of gonadectomy on disease onset and progression. DHEA
      treatment did not alter disease progression or survival in SOD1-G93A rats. Our
      results indicate that gonadal steroids or neurosteroids are not one of the
      possible modulators for the occurrence or disease progression in a rat model of
      ALS. Further analysis will be necessary to understand how sexual dimorphism is
      involved in ALS disease progression.

PMID- 22409358
TI  - Analysis of European case-control studies suggests that common inherited
      variation in mitochondrial DNA is not involved in susceptibility to amyotrophic
      lateral sclerosis.
AB  - While some cases of familial ALS can be entirely attributed to known inherited
      variation, the majority (~ 90%) are sporadic, where the cause(s) are not entirely
      understood. Both genetic and environmental factors may contribute to
      susceptibility. Mitochondrial damage, a common feature of neurodegenerative
      disease, is observed in most patients and inherited polymorphism in the
      mitochondrial genome has been suggested as a contributing factor. We used an
      economic and efficient method to test whether such involvement is probable. We
      genotyped 22 mtDNA coding region SNPs and sequenced the mtDNA hypervariable
      region 1 to determine the position of each mitochondrial genome within the
      genealogy of mitochondrial haplotypes in samples of ALS patients (n = 700) and
      controls (n = 462) from two European populations. We compared haplotype and
      haplogroup distribution in cases and controls drawn from the same populations. No
      statistical difference was observed between cases and controls at either the
      haplogroup or haplotype level (p = >=  0.2). In conclusion, it is unlikely that
      common, shared genetic variants in the mitochondrial genome contribute
      substantially to ALS. Combining the data with other studies will allow meta
      analysis to look for variants with modest effect sizes. The sequencing of
      complete mitochondrial genomes will be required to assess the role of rare
      mutations.

PMID- 22409359
TI  - Marked intrafamilial phenotypic variation in a family with SOD1 C111Y mutation.
AB  - Our objectives were to identify the disease-causing mutation in, and report on
      the clinical features of, a Japanese family that had coexisting phenotypes of
      amyotrophic lateral sclerosis and spinal muscular atrophy. The family comprised
      nine patients (six men and three women). We reviewed their clinical records and
      performed mutation analysis of the copper/zinc superoxide dismutase (SOD1) gene
      in some of these patients. The patients either had a rapid (n=7) or an extremely
      long (n=2) clinical course. The mean age at onset was 39.0+/-13.7 years (range 20
      68 years). The initial symptoms were bulbar palsy (n=2), upper (n=4) or lower
      (n=2) limb muscle weakness, or leg cramps (n=1). The total disease duration
      varied widely, ranging from one year to >69 years. We identified a SOD1 C111Y
      mutation among patients in this family. In conclusion, the family showed a marked
      intrafamilial phenotypic variation associated with the SOD1 C111Y mutation.
      Elucidating the biological basis of disease expression in patients with the SOD1
      C111Y mutation may provide us with useful information to develop therapeutic
      approaches and to prevent disease progression.

PMID- 22409360
TI  - Prevalence of Huntington's disease gene CAG repeat alleles in sporadic
      amyotrophic lateral sclerosis patients.
AB  - A higher prevalence of intermediate ataxin-2 CAG repeats in amyotrophic lateral
      sclerosis (ALS) patients has raised the possibility that CAG expansions in other
      polyglutamine disease genes could contribute to ALS neurodegeneration. We sought
      to determine whether expansions of the CAG repeat of the HTT gene that causes
      Huntington's disease, are associated with ALS. We compared the HTT CAG repeat
      length on a total of 3144 chromosomes from 1572 sporadic ALS patients and 4007
      control chromosomes, and also tested its possible effects on ALS-specific
      parameters, such as age and site of onset and survival rate. Our results show
      that the CAG repeat in the HTT gene is not a risk factor for ALS nor modifies its
      clinical presentation. These findings suggest that distinct neuronal degeneration
      processes are involved in these two different neurodegenerative disorders.

PMID- 22409361
TI  - Neuroanatomical patterns of cerebral white matter involvement in different motor
      neuron diseases as studied by diffusion tensor imaging analysis.
AB  - This study was designed to investigate differences of white matter (WM)
      involvement patterns in various motor neuron disorders (MND) by use of diffusion
      tensor imaging (DTI).DTI was acquired in ALS (n = 20), primary lateral sclerosis
      (n = 20), pure hereditary spastic paraparesis (HSP) (n = 20), and complicated HSP
      (n = 12). The data analysis was performed by voxelwise comparison of fractional
      anisotropy (FA) maps at group level together with fibre tracking in regions of
      interest (ROI) accompanied by tractwise fractional anisotropy statistics. DTI
      analysis revealed widespread patterns of alterations with a predominant
      deterioration of the motor system. These alterations encompassed, as the key
      structures, not only the corticospinal tracts (CST) but also distinct areas of
      the corpus callosum (CC), in particular its motor segment III. In conclusion,
      whole brain-based and tract-based DTI analysis was able to define a distinct WM
      pathoanatomy of different MND. These results may serve as an additional guidance
      in the identification of MRI-based parameters by showing a consistent CST and CC
      involvement, with differences in the extent of pathology, across a range of
      clinically different disorders. For potential future developments in MRI
      diagnostics in MND, a (perhaps multiparametric) ROI-based approach should include
      CST and the CC motor segment.

PMID- 22409362
TI  - Incidence of amyotrophic lateral sclerosis in Sicily: A population based study.
AB  - Our objective was to investigate incidence of amyotrophic lateral sclerosis (ALS)
      in Sicily, southern Italy, by means of a population based study. We included
      people with ALS resident in five Sicilian provinces, whose onset occurred in the
      two-year period 2005-2006 (population at 31 December 2006: 3,481,096
      inhabitants). A multisource case-finding procedure was adopted and patients were
      classified as affected by ALS according to revised El Escorial criteria. During
      the two-year surveillance period, 97 patients meeting eligibility criteria
      included 57 males (58.8%) and 40 females (41.2%). Crude annual incidence rate was
      1.4/100,000 person years (95% CI 1.33-1.47). The incidence rate was higher in
      males (1.71/100,000; CI 1.61-1.81) than in females (1.11/100,000; CI 1.01-1.21).
      Standardized incidence rate for the total population in the 45-74-years-old age
      group was 3.22 (CI 3.11-3.33). Prevalence rate was 6.0/100,000 (CI 5.97-6.03),
      higher in males (7.1/100,000; CI 7.02-7.18) than females (4.9/100,000; CI 4.86
      4.94). In conclusion, ALS rates observed in the present study are higher in males
      than females, with a peak of incidence at 70 years of age in both genders. These
      findings are consistent with those of other population based European studies.

PMID- 22409363
TI  - Stem cell niche: from concept to reality.

PMID- 22409364
TI  - Striping by striding: synthetic approaches toward pattern formation.

PMID- 22409365
TI  - beta-catenin in metastatic melanoma--the smoking gun reloaded.

PMID- 22409366
TI  - The Yin-Yang of RAF inhibitors.

PMID- 22409367
TI  - MicroRNAs and signaling, complex interaction by feedback loops.

PMID- 22409368
TI  - 2012 European guideline for the management of anogenital warts.
AB  - BACKGROUND: Although new HPV vaccines have been developed and are in the process
      of implementation, anogenital warts remain a very frequent problem in clinical
      practice. OBJECTIVE: We wished to update previously published European guidelines
      for the management of anogenital warts. METHODS: We performed a systematic review
      of randomized controlled trials for anogenital warts. The primary data were
      analyzed and collated, and the findings were formulated within the structure of a
      clinical guideline. The IUSTI Europe Editorial Board reviewed the draft guideline
      which was also posted on the web for comments which we incorporated into the
      final version of the guideline. RESULTS: The data confirm that only surgical
      therapies have primary clearance rates approaching 100%. Recurrences, including
      new lesions at previously treated or new sites, occur after all therapies, and
      rates are often 20-30% or more. All therapies are associated with local skin
      reactions including itching, burning, erosions and pain. CONCLUSIONS: Physicians
      treating patients with genital warts should develop their own treatment
      algorithms which include local practice and recommendations. Such patient level
      management protocols should incorporate medical review of cases at least every 4
      weeks, with switching of treatments if an inadequate response is observed. First
      episode patients should be offered sexually transmitted disease screening.
      Management should include partner notification and health promotion.

PMID- 22409369
TI  - Magnetically guided nano-micro shaping and slicing of silicon.
AB  - Silicon is one of the most important materials for modern electronics, telecom,
      and photovoltaic (PV) solar cells. With the rapidly expanding use of Si in the
      global economy, it would be highly desirable to reduce the overall use of Si
      material, especially to make the PVs more affordable and widely used as a
      renewable energy source. Here we report the first successful direction-guided,
      nano/microshaping of silicon, the intended direction of which is dictated by an
      applied magnetic field. Micrometer thin, massively parallel silicon sheets, very
      tall Si microneedles, zigzag bent Si nanowires, and tunnel drilling into Si
      substrates have all been demonstrated. The technique, utilizing narrow array of
      Au/Fe/Au trilayer etch lines, is particularly effective in producing only
      micrometer-thick Si sheets by rapid and inexpensive means with only 5 MUm level
      slicing loss of Si material, thus practically eliminating the waste (and also the
      use) of Si material compared to the ~200 MUm kerf loss per slicing and ~200 MUm
      thick wafer in the typical saw-cut Si solar cell preparation. We expect that such
      nano/microshaping will enable a whole new family of novel Si geometries and
      exciting applications, including flexible Si circuits and highly antireflective
      zigzag nanowire coatings.

PMID- 22409370
TI  - Cardiac magnetic resonance imaging in children with chronic kidney disease and
      renal transplantation.
AB  - CV disease is the major cause of death in patients with CKD. Recently, CMR
      imaging emerges as a complementary method providing advantages in cardiac
      assessment; however, data on CMR in pediatric CKD are scarce. We performed CMR in
      15 children: two with CKD, six on peritoneal dialysis, seven on hemodialysis, and
      in 18 children 5.1 (0.4-15.4) yr after kidney Tx. Eight children underwent CMR
      six months before and after Tx. Results are presented as mean z score +/- SD. LV
      EF was higher and in the normal range in Tx patients compared with CKD (-0.3 +/-
      1 vs. -2.1 +/- 1.6, respectively, p < 0.05), whereas RV EF was similar (-0.9 +/-
      1.4 vs. -0.9 +/- 1.8, p = n.s.). End-diastolic and end-systolic LV volume index
      (0 +/- 1.7 vs. 2.1 +/- 3.1; 0.2 +/- 1.2 vs. 3.1 +/- 3.7, both p < 0.05) and LV
      mass index (1.4 +/- 1.5 vs. 3.4 +/- 2.9, p < 0.05) were lower in Tx children. All
      parameters improved in the eight children after Tx. In conclusion, our CMR
      analysis suggests marked improvement of cardiac function and morphology in
      children after kidney Tx. CMR might be an appropriate complementary method for
      measuring detailed cardiac status in children with CKD.

PMID- 22409371
TI  - Acute exacerbations of COPD in the United States: inpatient burden and predictors
      of costs and mortality.
AB  - Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a
      leading cause of hospitalizations in the United States and the major cost driver
      of COPD. This study determined the national inpatient burden of AECOPD and
      assessed the association of co-morbidities and hospital characteristics with
      inpatient costs and mortality. Discharge records from the Agency for Healthcare
      Research and Quality (AHRQ) Healthcare Cost and Utilization Project (HCUP)
      Nationwide Inpatient Sample for 2006 was utilized. Outcomes of costs and
      mortality were assessed for AECOPD hospitalizations in cases >=40 years of age.
      Multivariate regression analyses using a generalized linear model framework were
      conducted to determine predictors of inpatient costs and mortality controlling
      for patient demographics, primary payer, co-morbidity index, length of stay,
      hospital region, mechanical ventilation, and admission period. Overall, 1,254,703
      hospitalizations for AECOPD were observed with mean costs of $9545(+/-12,700) and
      total costs of $11.9 billion. In-hospital mortality was 4.3% (N = 53,748).
      Discharges averaged 70.6 (+/-11.9) years of age. The majority were female (52.8%)
      and of white race (83.6% of reported race). Several co-morbidities were
      significantly associated with both costs and mortality (p < 0.001): acute
      myocardial infarction; congestive heart failure; cerebrovascular disease; lung
      cancer; cardiac arrhythmias; pulmonary circulation disorders; and weight loss.
      Significantly higher costs (p < 0.001) were associated with large and urban
      hospitals. The importance of co-morbidities in AECOPD is indicated in their
      association with prognosis and inpatient costs. Future research should determine
      if better management of these conditions can favorably impact the COPD disease
      burden.

PMID- 22409372
TI  - Association between circulating cytokine levels, diabetes and insulin resistance
      in a population-based sample (CoLaus study).
AB  - OBJECTIVE: The associations between inflammation, diabetes and insulin resistance
      remain controversial. Hence, we assessed the associations between diabetes,
      insulin resistance (using HOMA-IR) and metabolic syndrome with the inflammatory
      markers high-sensitive C-reactive protein (hs-CRP), interleukin-1 beta (IL
      1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha).
      DESIGN: Cross-sectional study. PARTICIPANTS: Two thousand eight hundred and
      eighty-four men and 3201 women, aged 35-75, participated in this study. METHODS:
      C-reactive protein was assessed by immunoassay and cytokines by multiplexed flow
      cytometric assay. In a subgroup of 532 participants, an oral glucose tolerance
      test (OGTT) was performed to screen for impaired glucose tolerance (IGT).
      RESULTS: IL-6, TNF-alpha and hs-CRP were significantly and positively correlated
      with fasting plasma glucose (FPG), insulin and HOMA-IR. Participants with
      diabetes had higher IL-6, TNF-alpha and hs-CRP levels than participants without
      diabetes; this difference persisted for hs-CRP after multivariate adjustment.
      Participants with metabolic syndrome had increased IL-6, TNF-alpha and hs-CRP
      levels; these differences persisted after multivariate adjustment. Participants
      in the highest quartile of HOMA-IR had increased IL-6, TNF-alpha and hs-CRP
      levels; these differences persisted for TNF-alpha and hs-CRP after multivariate
      adjustment. No association was found between IL-1beta levels and all diabetes and
      insulin resistance markers studied. Finally, participants with IGT had higher hs
      CRP levels than participants with a normal OGTT, but this difference disappeared
      after controlling for body mass index (BMI). CONCLUSION: We found that subjects
      with diabetes, metabolic syndrome and increased insulin resistance had increased
      levels of IL6, TNF-alpha and hs-CRP, while no association was found with IL
      1beta. The increased inflammatory state of subjects with IGT is partially
      explained by increased BMI.

PMID- 22409373
TI  - Chemopreventive efficacy of hesperetin (citrus flavonone) against 1,2
      dimethylhydrazine-induced rat colon carcinogenesis.
AB  - BACKGROUND: Colorectal carcinogenesis is one of the most common cancers/lethal
      diseases. Chronic inflammation is considered a risk factor for colorectal cancer.
      Hesperetin, a flavonone found in citrus fruits and oranges is shown to possess
      potent growth inhibitory effects against various human cancer cells. It possesses
      anti-inflammatory and antioxidant properties. AIM OF THE SCOPE: In the present
      study, we have evaluated the chemopreventive efficacy of hesperetin against rat
      colon carcinogenesis in male Wistar rats. METHODS: Group 1 served as control,
      received modified pellet diet and group 2 rats received 20 mg/kg body weight of
      hesperetin p.o. every day. Groups 3-6 rats were given subcutaneous injections of
      1,2-dimethylhydrazine (DMH, 20 mg/kg body weight) once a week for 15 consecutive
      weeks. In addition, rats in group 4 received hesperetin as in group 2 for the
      first 15 weeks (initiation), group 5 rats received hesperetin as in group 2 after
      the last injection of DMH and continued till the end of the experimental period
      (postinitiation). Group 6 rats received hesperetin as in group 2 throughout the
      entire experimental period of 32 weeks. RESULTS: Detection of cell proliferation
      markers such as proliferating cell nuclear antigen (PCNA) (immunohistochemistry),
      argyrophilic nucleolar organizer regions (AgNORs) (silver staining); apoptosis
      (immunoblotting and immunohistochemistry); angiogenic growth factors (ELISA)
      indicated decreased cell proliferation and increased apoptotic markers in the
      colon. In addition, decreased angiogenic growth factors such as vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF),
      epidermal growth factor (EGF), and downregulation of mRNA Cyclooxygenase-2 (COX
      2) expressions were observed in mucosal and fecal samples of hesperetin
      supplemented rats. CONCLUSIONS: Hesperetin supplementation showed an inhibition
      of cell proliferation markers, angiogenic growth factors, COX-2 mRNA expression
      and induction of apoptosis. Thus, hesperetin can be used as a potent
      chemopreventive agent against DMH-induced colon cancer.

PMID- 22409374
TI  - Telehomecare communication and self-care in chronic conditions: moving toward a
      shared understanding.
AB  - BACKGROUND: Remote telemonitoring of patients' vital signs is a rapidly
      increasing practice. Although methods of communication in remote electronic
      monitoring differ from those in traditional home health care, the understanding
      shared by the nurse, patient, and family members remains the same: patients' self
      care behaviors affect exacerbations of chronic health conditions. The purpose of
      this paper is to examine the relationship between communication and information
      integration into the daily lives of patients with chronic illnesses and offer
      best practice recommendations for telehomecare nurses (THN). METHODS: The
      original study used the Social Relations Model to examine relationships within 43
      triads composed of patients with chronic conditions, home helpers, and their
      nurse involved in telehomecare at three Veterans Health Administration sites.
      This secondary descriptive and correlational analysis compared 43 patients' and
      nine THNs' ratings of themselves and each other on communication (frequency,
      timeliness, and understanding) and the use of patients' daily telemonitored
      information. RESULTS: There was almost no correlation between patients'
      perception of THNs' communication (frequency [r=0.05], timeliness [r=0.09], and
      understandability [r=0.03]) and patients' integration of information into daily
      health practices. However, significant correlations were found between the THNs'
      perception of patients' communication frequency and timeliness, and integration,
      (p=0.02; p<0.001) respectively. CONCLUSIONS: This study suggests that frequent
      phone communication may lead the remote THN to believe patients are integrating
      blood pressure, weight, and other information into daily self-care behaviors,
      when in fact the patient reports that they are not. The influence of a halo
      effect on the THN may cloud an accurate perception of what is actually occurring.
      Remote communication may require more attention to THNs educating patients about
      shared understandings when using telemonitoring. Best practices for THN should
      include explicit goals and intentions for telemonitored home care with
      individualized instructions about how to use the information for self-care.

PMID- 22409375
TI  - Infrequent detection of papillomaviral DNA within canine cutaneous squamous cell
      carcinomas, haemangiosarcomas and healthy skin on the ventrum of dogs.
AB  - BACKGROUND: Canine squamous cell carcinomas (SCCs) most frequently develop on the
      ventral abdomen and are thought to be caused by ultraviolet (UV) light.
      Papillomaviruses (PVs) have been associated with cutaneous SCCs in multiple
      species, including dogs. HYPOTHESIS: That PVs act as cofactors in canine UV
      induced SCCs. ANIMALS: The study was performed on skin from the ventrum of 60
      dogs. These samples included 20 SCCs, 20 haemangiosarcomas and 20 samples of
      clinically normal skin. Two canine viral plaques were included as positive
      controls for PV. METHODS: PCR was used to amplify PV DNA from all samples.
      Primers used included two sets of consensus primers and two sets of primers that
      were designed specifically to amplify PV DNA sequences detected in the viral
      plaques. RESULTS: The MY09/11 consensus primers amplified PV DNA from both viral
      plaques. One plaque contained a DNA sequence (CfPV-JM) that had been previously
      reported from a dog with multiple cutaneous SCCs. The other plaque contained a
      previously unreported PV DNA sequence. No PV DNA was amplified by either
      consensus primer from any of the ventrum skin samples. Primers designed
      specifically to amplify the CfPV-JM sequence amplified DNA from one SCC, but no
      other sample. No PV DNA was amplified using the other specific PCR primer set.
      CONCLUSIONS AND CLINICAL IMPORTANCE: These results do not support a significant
      role for PVs in SCC development from the ventrum of dogs. However, they
      contribute another PV sequence to the list of PVs that have been associated with
      viral plaque development in dogs.

PMID- 22409377
TI  - Metabolites from Aspergillus fumigatus, an endophytic fungus associated with
      Melia azedarach, and their antifungal, antifeedant, and toxic activities.
AB  - Thirty-nine fungal metabolites 1-39, including two new alkaloids, 12beta-hydroxy
      13alpha-methoxyverruculogen TR-2 (6) and 3-hydroxyfumiquinazoline A (16), were
      isolated from the fermentation broth of Aspergillus fumigatus LN-4, an endophytic
      fungus isolated from the stem bark of Melia azedarach. Their structures were
      elucidated on the basis of detailed spectroscopic analysis (mass spectrometry and
      one- and two-dimensional NMR experiments) and by comparison of their NMR data
      with those reported in the literature. These isolated compounds were evaluated
      for in vitro antifungal activities against some phytopathogenic fungi, toxicity
      against brine shrimps, and antifeedant activities against armyworm larvae
      (Mythimna separata Walker). Among them, sixteen compounds showed potent
      antifungal activities against phytopathogenic fungi (Botrytis cinerea, Alternaria
      solani, Alternaria alternata, Colletotrichum gloeosporioides, Fusarium solani,
      Fusarium oxysporum f. sp. niveum, Fusarium oxysporum f. sp. vasinfectum, and
      Gibberella saubinettii), and four of them, 12beta-hydroxy-13alpha
      methoxyverruculogen TR-2 (6), fumitremorgin B (7), verruculogen (8), and helvolic
      acid (39), exhibited antifungal activities with MIC values of 6.25-50 MUg/mL,
      which were comparable to the two positive controls carbendazim and hymexazol. In
      addition, of eighteen that exerted moderate lethality toward brine shrimps,
      compounds 7 and 8 both showed significant toxicities with median lethal
      concentration (LC(50)) values of 13.6 and 15.8 MUg/mL, respectively. Furthermore,
      among nine metabolites that were found to possess antifeedant activity against
      armyworm larvae, compounds 7 and 8 gave the best activity with antifeedant
      indexes (AFI) of 50.0% and 55.0%, respectively. Structure-activity relationships
      of the metabolites were also discussed.

PMID- 22409379
TI  - Outcomes in older adults with acute lymphoblastic leukaemia (ALL): results from
      the international MRC UKALL XII/ECOG2993 trial.
AB  - Although the incidence rate of acute lymphoblastic leukaemia (ALL) is slightly
      higher in older than in younger adults, response rates to induction chemotherapy
      and survival rates are poorer. The contribution of disease-related versus
      treatment-related factors remains unclear. We analysed 100 older patients (aged
      55-65 years) treated on the UKALLXII/ECOG2993 trial compared with 1814 younger
      patients (aged 14-54 years). Baseline characteristics, induction chemotherapy
      course, infections, drug reductions and survival outcomes were compared. There
      were more Philadelphia-positive (Ph+) patients in the older group (28% vs. 17%, P
      = 0.02), and a trend towards higher combined cytogenetic risk score (46% vs. 35%,
      P = 0.07). The complete remission rate in older patients was worse (73% vs. 93%,
      P < 0.0001) as was 5-year overall survival (21% vs. 41%, P < 0.0001) and event
      free survival (EFS) (19% vs. 37%, P < 0.0001). Older patients had more infections
      during induction (81% vs. 70%, P = 0.05), and drug reductions (46% vs. 28%, P =
      0.0009). Among older patients, Ph+ and cytogenetic risk category as well as
      infection during induction predicted for worse EFS. Poorer outcomes in these
      patients are partly due to cytogenetic risk, but there is significant morbidity
      and mortality during induction chemotherapy with frequent delays and drug
      reductions. New approaches, including better risk stratification and use of
      targeted therapies, could improve treatment for these patients.

PMID- 22409376
TI  - Structural studies of E73 from a hyperthermophilic archaeal virus identify the
      "RH3" domain, an elaborated ribbon-helix-helix motif involved in DNA recognition.
AB  - Hyperthermophilic archaeal viruses, including Sulfolobus spindle-shaped viruses
      (SSVs) such as SSV-1 and SSV-Ragged Hills, exhibit remarkable morphology and
      genetic diversity. However, they remain poorly understood, in part because their
      genomes exhibit limited or unrecognizable sequence similarity to genes with known
      function. Here we report structural and functional studies of E73, a 73-residue
      homodimeric protein encoded within the SSV-Ragged Hills genome. Despite lacking
      significant sequence similarity, the nuclear magnetic resonance (NMR) structure
      reveals clear similarity to ribbon-helix-helix (RHH) domains present in numerous
      proteins involved in transcriptional regulation. In vitro double-stranded DNA
      (dsDNA) binding experiments confirm the ability of E73 to bind dsDNA in a
      nonspecific manner with micromolar affinity, and characterization of the K11E
      variant confirms the location of the predicted DNA binding surface. E73 is
      distinct, however, from known RHH domains. The RHH motif is elaborated upon by
      the insertion of a third helix that is tightly integrated into the structural
      domain, giving rise to the "RH3" fold. Within the homodimer, this helix results
      in the formation of a conserved, symmetric cleft distal to the DNA binding
      surface, where it may mediate protein-protein interactions or contribute to the
      high thermal stability of E73. Analysis of backbone amide dynamics by NMR
      provides evidence of a rigid core, fast picosecond to nanosecond time scale NH
      bond vector motions for residues located within the antiparallel beta-sheet
      region of the proposed DNA-binding surface, and slower microsecond to millisecond
      time scale motions for residues in the alpha1-alpha2 loop. The roles of E73 and
      its SSV homologues in the viral life cycle are discussed.

PMID- 22409381
TI  - Light-harvesting cross-linked polymers for efficient heterogeneous
      photocatalysis.
AB  - Nonporous, phosphorescent cross-linked polymers (Ru-CP and Ir-CP) were
      synthesized via Pd-catalyzed Sonogashira cross-coupling reactions between tetra(p
      ethynylphenyl)methane and dibrominated Ru(bpy)(3)(2+) or Ir(ppy)(2)(bpy)(+),
      respectively. The resultant particulate cross-linked polymer (CP) materials have
      very high catalyst loadings (76.3 wt % for Ru-CP and 71.6 wt % for Ir-CP), and
      are nonporous with negligibly small surface areas (2.9 m(2)/g for Ru-CP and 2.7
      m(2)/g for Ir-CP). Despite their nonporous nature, the insoluble CP materials
      serve as highly active and recyclable heterogeneous photocatalysts for a range of
      organic transformations such as aza-Henry reaction, aerobic amine coupling, and
      dehalogenation of benzyl bromoacetate. An efficient light-harvesting mechanism,
      which involves collection of photons by exciting the (3)MLCT states of the
      phosphors and migration of the excited states to the particle surface, is
      proposed to account for the very high catalytic activities of these nonporous
      CPs. Steady-state and time-resolved emission data, as well as the reduced
      catalytic activity of Os(bpy)(3)(2+)-doped Ru-CPs supports efficient excited
      state migration for the CP frameworks. This work uncovers a new strategy in
      designing highly efficient photocatalysts based on light-harvesting cross-linked
      polymers.

PMID- 22409380
TI  - Influence of Rangelia vitalii (Apicomplexa: Piroplasmorida) on copper, iron, and
      zinc bloodstream levels in experimentally infected dogs.
AB  - The aim of this study was to evaluate the concentrations of copper, iron, and
      zinc in blood serum of dogs experimentally infected with Rangelia vitalii (n  = 
      7) compared with uninfected controls (n  =  5). Serum metal levels were
      determined in blood samples collected at days 0, 10, 15, and 20 post-infection
      (PI). Inductively coupled plasma optical emission spectrometry was used to
      measure the levels of copper, iron, and zinc. Significant differences (P < 0.05)
      were observed among groups PI. Increased levels of copper and decreased levels of
      iron and zinc were observed in the infected animals. The infection by R. vitalii
      may, therefore, alter the serum metal levels, resulting in metabolic disorders in
      dogs. These metals are directly involved in many enzymatic systems; accordingly,
      alterations in their blood concentrations may also influence the pathogenesis of
      disease.

PMID- 22409382
TI  - Digital UV/IR photography for tattoo evaluation in mummified remains.
AB  - The presence and location of tattoos can be an important component in the
      identification of remains in the extended postmortem period if remnants of skin
      persist. However, when there is significant mummification, visualization of
      tattoos can be problematic. Multiple methods have been proposed to make tattoos
      more visible, but all have limitation. In this case report, a mummified body was
      discovered. The presumptive victim was reported to have a small tattoo on her
      hand but it was not visible to the naked eye. The hand was photographed using
      ultraviolet (UV) and infrared (IR) light. A tattoo matching the description was
      noted in the photographs. In contrast to film-based IR and UV photography,
      digital UV and IR photography allows rapid visual evaluation of results and
      optimization of image utility. The ability to quickly modify photographic
      parameters quickly greatly increases the utility of IR and UV photography in the
      autopsy suite.

PMID- 22409383
TI  - Impact of ustekinumab on health-related quality of life in Japanese patients with
      moderate-to-severe plaque psoriasis: results from a randomized, double-blind,
      placebo-controlled phase 2 / 3 trial.
AB  - This study evaluates the effect of ustekinumab on health-related quality of life
      (HRQoL) in Japanese patients with moderate-to-severe plaque psoriasis through 64
      weeks. A total of 158 patients were randomized to receive subcutaneous injections
      of ustekinumab 45 mg (n = 64) or 90 mg (n = 62) at weeks 0, 4, and every-12
      weeks, or placebo (n = 32) with crossover to ustekinumab at week 12. Secondary
      study endpoints included change in Dermatology Life Quality Index (DLQI) at week
      12. Other assessments included the 36-item Short Form health survey to assess
      Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, and
      Psoriasis Disability Index (PDI), a psoriasis-specific instrument to assess
      HRQoL. Baseline demographic and disease characteristics were similar across
      randomized treatment groups. Ustekinumab-treated patients had significantly
      greater mean improvements in DLQI from baseline to week 12 (45 mg: 8.0 +/- 6.5;
      90 mg: 7.4 +/- 6.5) than placebo-treated patients (0.3 +/- 5.3; P < 0.0001 for
      each), and these improvements were maintained through week 64. Also at week 12,
      significant improvements from baseline in PDI scores were observed in ustekinumab
      treated patients (45 mg: 8.6 +/- 9.6; 90 mg: 12.0 +/- 11.8) compared with placebo
      treated patients (-0.1 +/- 4.2). Improvements in the PCS (45 mg: 7.8 +/- 14.5; 90
      mg: 5.1 +/- 12.0) and MCS (45 mg: 5.3 +/- 9.8; 90 mg: 5.8 +/- 10.5) scores were
      also observed in ustekinumab-treated patients at week 12. Placebo-treated
      patients who crossed-over to ustekinumab achieved improvements in HRQoL
      comparable to those observed in patients originally randomized to ustekinumab.
      Ustekinumab significantly improves HRQoL in Japanese patients with moderate-to
      severe plaque psoriasis through week 64.

PMID- 22409384
TI  - Spectroscopic, structural, and theoretical studies of halide complexes with a
      urea-based tripodal receptor.
AB  - A urea-based tripodal receptor L substituted with p-cyanophenyl groups has been
      studied for halide anions using (1)H NMR spectroscopy, density functional theory
      (DFT) calculations, and X-ray crystallography. The (1)H NMR titration studies
      suggest that the receptor forms a 1:1 complex with an anion, showing a binding
      trend in the order of fluoride > chloride > bromide > iodide. The interaction of
      a fluoride anion with the receptor was further confirmed by 2D NOESY and (19)F
      NMR spectroscopy in DMSO-d(6). DFT calculations indicate that the internal halide
      anion is held by six NH...X interactions with L, showing the highest binding
      energy for the fluoride complex. Structural characterization of the chloride,
      bromide, and silicon hexafluoride complexes of [LH(+)] reveals that the anion is
      externally located via hydrogen bonding interactions. For the bromide or chloride
      complex, two anions are bridged with two receptors to form a centrosymmetric
      dimer, while for the silicon hexafluoride complex, the anion is located within a
      cage formed by six ligands and two water molecules.

PMID- 22409385
TI  - A multicenter, double-blind, placebo-controlled trial of autologous fibroblast
      therapy for the treatment of nasolabial fold wrinkles.
AB  - BACKGROUND: Changes associated with aging are partly due to loss of collagen and
      elastin. Treatment with autologous fibroblasts grown in culture (azficel-T) can
      help correct the appearance of aging by replacing lost dermal constituents.
      OBJECTIVE: To demonstrate the safety and effectiveness of autologous fibroblasts
      in the treatment of nasolabial fold (NLF) wrinkles. METHODS AND MATERIALS: Adults
      with moderate to very severe NLF wrinkles were randomized to receive three
      treatments with autologous fibroblasts or placebo at 5-week intervals. Blinded
      evaluators and subjects assessed efficacy using a validated wrinkle assessment
      scale. RESULTS: Three hundred seventy-two subjects were enrolled and underwent
      treatment. Seventy-eight percent of subjects treated with autologous fibroblast
      therapy and 48% of subjects treated with placebo achieved at least a 1-point
      improvement on the subject assessment at 6 months (p < 0.001), and 64% of
      subjects treated with autologous fibroblast therapy and 36% of those treated with
      placebo showed at least a 1-point improvement evaluator's assessment (p < 0.001).
      Adverse events were generally mild, and the treatment was well tolerated.
      CONCLUSION: Autologous fibroblast therapy is safe and effective for the treatment
      of NLF wrinkles. The availability of autologous cell therapy marks the beginning
      of a new phase in aesthetic therapy.

PMID- 22409386
TI  - Nanoscale InGaSb heterostructure membranes on Si substrates for high hole
      mobility transistors.
AB  - As of yet, III-V p-type field-effect transistors (p-FETs) on Si have not been
      reported, due partly to materials and processing challenges, presenting an
      important bottleneck in the development of complementary III-V electronics. Here,
      we report the first high-mobility III-V p-FET on Si, enabled by the epitaxial
      layer transfer of InGaSb heterostructures with nanoscale thicknesses.
      Importantly, the use of ultrathin (thickness, ~2.5 nm) InAs cladding layers
      results in drastic performance enhancements arising from (i) surface passivation
      of the InGaSb channel, (ii) mobility enhancement due to the confinement of holes
      in InGaSb, and (iii) low-resistance, dopant-free contacts due to the type III
      band alignment of the heterojunction. The fabricated p-FETs display a peak
      effective mobility of ~820 cm(2)/(V s) for holes with a subthreshold swing of
      ~130 mV/decade. The results present an important advance in the field of III-V
      electronics.

PMID- 22409387
TI  - Differences of cardiac output measurements by open-circuit acetylene uptake in
      pulmonary arterial hypertension and chronic thromboembolic pulmonary
      hypertension: a cohort study.
AB  - BACKGROUND: As differences in gas exchange between pulmonary arterial
      hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) have
      been demonstrated, we asked if cardiac output measurements determined by
      acetylene (C2H2) uptake significantly differed in these diseases when compared to
      the thermodilution technique. METHOD: Single-breath open-circuit C2H2 uptake,
      thermodilution, and cardiopulmonary exercise testing were performed in 72 PAH and
      32 CTEPH patients. RESULTS: In PAH patients the results for cardiac output
      obtained by the two methods showed an acceptable agreement with a mean difference
      of -0.16 L/min (95% CI -2.64 to 2.32 L/min). In contrast, the agreement was
      poorer in the CTEPH group with the difference being -0.56 L/min (95% CI -4.96 to
      3.84 L/min). Functional dead space ventilation (44.5 +/- 1.6 vs. 32.2 +/- 1.4%, p
      < 0.001) and the mean arterial to end-tidal CO2 gradient (9.9 +/- 0.8 vs. 4.1 +/-
      0.5 mmHg, p < 0.001) were significantly elevated among CTEPH patients.
      CONCLUSION: Cardiac output evaluation by the C2H2 technique should be interpreted
      with caution in CTEPH, as ventilation to perfusion mismatching might be more
      relevant than in PAH.

PMID- 22409388
TI  - A randomized, 14-day, double-blind study evaluating conversion from
      hydrocodone/acetaminophen (Vicodin) to buprenorphine transdermal system 10 MUg/h
      or 20 MUg/h in patients with osteoarthritis pain.
AB  - OBJECTIVE: The objective of this study was to evaluate continued pain control and
      tolerability of converting patients from Vicodin (hydrocodone/acetaminophen;
      HCD/APAP) to the buprenorphine transdermal system (BTDS). METHODS: Adult patients
      with pain from osteoarthritis receiving a stable dosage of HCD/APAP (i.e., 15 -
      30 mg hydrocodone/day) were switched to an equivalent or near-equivalent dosage
      of open-label Vicodin for 7 days. Patients maintaining acceptable analgesia were
      stratified based on their Vicodin dosage and randomized to receive either
      titratable BTDS 10 MUg/h or fixed-dose BTDS 20 MUg/h. The primary efficacy
      variable was completion of the 14-day double-blind phase. Tolerability was
      assessed. RESULTS: A total of 84.3% of patients met the primary end point,
      completion of the 14-day double-blind phase (167/198 patients, 95% CI 79.3 -
      89.4). Adverse events were consistent with those associated with the use of
      opioid analgesics and transdermal patches. CONCLUSION: There was a similar
      analgesic and tolerability profile when patients treated with Vicodin for
      osteoarthritis pain were switched to 7-day BTDS treatment.

PMID- 22409389
TI  - Development in children with achondroplasia: a prospective clinical cohort study.
AB  - AIM: Achondroplasia is characterized by delays in the development of
      communication and motor skills. While previously reported developmental profiles
      exist across gross motor, fine motor, feeding, and communication skills, there
      has been no prospective study of development across multiple areas
      simultaneously. METHOD: This Australasian population-based study utilized a
      prospective questionnaire to quantify developmental data for skills in children
      born from 2000 to 2009. Forty-eight families from Australia and New Zealand were
      asked to report every 3 months on their child's attainment of 41 milestones.
      Results include reference to previously available prospective information.
      RESULTS: Information from questionnaires was used to develop an achondroplasia
      specific developmental recording form. The 25th, 50th, 75th, and 90th centiles
      were plotted to offer clear guidelines for development across gross motor, fine
      motor, feeding, and communication skills in children with achondroplasia.
      INTERPRETATIONS: Consistent with results from previous research, children with
      achondroplasia are delayed in development of gross motor and ambulatory skills.
      Young children with achondroplasia demonstrate a number of unique movement
      strategies that appear compensatory for the biomechanical changes. While delays
      were seen in development of later communication items, there were fewer delays
      seen across development of early communication, fine motor, and feeding skills.

PMID- 22409390
TI  - Empowering leaders optimize working conditions for engagement: a multilevel
      study.
AB  - Using a multilevel framework, this study examined the role of empowering
      leadership at the group level by fire brigade captains in facilitating the
      individual level motivational processes that underpin work engagement in
      volunteer firefighters. Anonymous mail surveys were completed by 540 volunteer
      firefighters from 68 fire brigades and, separately, by 68 brigade captains. As
      predicted on the basis of the Job Demands-Resources model, increased levels of
      cognitive demands and cognitive resources partially mediated the relationship
      between empowering leadership and work engagement. In a three-way Leadership *
      Demands * Resources interaction, empowering leadership also had the effect of
      optimizing working conditions for engagement by strengthening the positive effect
      of a work context in which both cognitive demands and cognitive resources were
      high. Our findings shed light on a process through which leaders can empower
      workers and enhance well-being: via their influence on and interaction with the
      work environment. They also underscore the need to examine work engagement from a
      multilevel theoretical perspective.

PMID- 22409391
TI  - Racial/ethnic harassment and discrimination, its antecedents, and its effect on
      job-related outcomes.
AB  - A general model of workplace prejudice acts, their antecedents, and their
      consequences is proposed and examined in the context of racial/ethnic harassment
      and discrimination (REHD). Antecedents proposed and tested here include context
      and climate, whereas consequences proposed and tested here include work,
      supervisor, and opportunity satisfaction and turnover intentions. The theoretical
      model is first tested and cross-validated in two ethnically diverse subsamples
      (approximately 2,000 each). Then, hierarchical multigroup modeling was conducted
      to determine whether the relationships among REHD, its antecedents, and its
      outcomes are equivalent across five racial/ethnic groups (N = 1,000 per group) in
      the U.S. military. This addresses the issue of differential exposure (i.e.,
      varying amounts of stressors across groups) versus differential vulnerability
      (i.e., discrepant impact of a stressor on outcomes across groups) across
      racial/ethnic groups. Consistent with expectations, results suggest that although
      racial/ethnic groups differ in their mean exposure to REHD, the relationships
      among REHD and its outcomes are the same across race/ethnicity, supporting the
      differential exposure view. In addition, the results show some differences
      between antecedents and REHD across race/ethnicity.

PMID- 22409393
TI  - Promotion of low-humidity proton conduction by controlling hydrophilicity in
      layered metal-organic frameworks.
AB  - We controlled the hydrophilicity of metal-organic frameworks (MOFs) to achieve
      high proton conductivity and high adsorption of water under low humidity
      conditions, by employing novel class of MOFs,
      {NR(3)(CH(2)COOH)}[MCr(ox)(3)].nH(2)O (abbreviated as R-MCr, where R = Me
      (methyl), Et (ethyl), or Bu (n-butyl), and M = Mn or Fe): Me-FeCr, Et-MnCr, Bu
      MnCr, and Bu-FeCr. The cationic components have a carboxyl group that functions
      as the proton carrier. The hydrophilicity of the cationic ions was tuned by the
      NR(3) residue to decrease with increasing bulkiness of the residue:
      {NMe(3)(CH(2)COOH)}(+) > {NEt(3)(CH(2)COOH)}(+) > {NBu(3)(CH(2)COOH)}(+). The
      proton conduction of the MOFs increased with increasing hydrophilicity of the
      cationic ions. The most hydrophilic sample, Me-FeCr, adsorbed a large number of
      water molecules and showed a high proton conductivity of ~10(-4) S cm(-1), even
      at a low humidity of 65% relative humidity (RH), at ambient temperature. Notably,
      this is the highest conductivity among the previously reported proton-conducting
      MOFs that operate under low RH conditions.

PMID- 22409394
TI  - Comparison of root resorption between self-ligating and conventional preadjusted
      brackets using cone beam computed tomography.
AB  - OBJECTIVE: To compare the magnitude of external apical root resorption (EARR) of
      incisors in patients undergoing the initial phase of orthodontic treatment with
      two sets of brackets. MATERIALS AND METHODS: According to the results of the
      power analysis for sample size calculation, 19 Angle Class I patients (anterior
      crowding: 3 to 5 mm; mean age: 20.6 years) were included in the study and
      randomly divided into two groups: group I (n  =  11, self-ligating brackets) and
      group II (n  =  8, conventional preadjusted brackets). The degree of EARR was
      detected in 152 upper and lower incisors by using cone-beam computed tomography
      (CBCT) scans and a three-dimensional program (Dolphin 11.5, Dolphin Imaging &
      Management Solutions, Chatsworth, Calif) with 25% level of sensitivity. The CBCT
      scans were obtained before (T1) and 6 months after initiation of treatment (T2).
      Differences between and within groups were analyzed by nonpaired and paired t
      test, respectively, with 5% significance level. RESULTS: Significant differences
      were found for both groups between T1 and T2. However, no differences in the
      degree of EARR were detected between the groups studied. CONCLUSIONS: Although
      EARR has occurred in all teeth evaluated, the bracket design (self-ligating or
      conventional) did not demonstrate any influence on the results observed.

PMID- 22409395
TI  - Self-ligating vs conventional brackets as perceived by orthodontists.
AB  - OBJECTIVE: To determine if there are significant clinical differences between
      self-ligating brackets (SLB) and conventional brackets (CB) during orthodontic
      treatment, as perceived by orthodontists. MATERIALS AND METHODS: A survey was
      developed and distributed to evaluate how SLB compare to CB in terms of
      orthodontists' perceptions (n  =  430). RESULTS: SLB were preferred during the
      initial stage of treatment based on the shorter adjustment appointments and
      faster initial treatment progress they provided (P < .0001). On the other hand,
      practitioners preferred CB during the finishing and detailing stages of treatment
      (P < .0001). CB were also preferred over SLB because they were cheaper and
      resulted in fewer emergency appointments. CONCLUSIONS: The orthodontists'
      preference was significantly influenced by (1) the proportion of patients treated
      with SLB (P < .0001), (2) the number of cases it took them to become accustomed
      to SLB (P < .0001), and (3) the average appointment intervals associated with SLB
      (P < .0001).

PMID- 22409396
TI  - Cutis laxa-like mycosis fungoides.
AB  - Mycosis fungoides is the most common form of primary cutaneous T-cell lymphoma.
      Several clinical and clinicopathological variants of mycosis fungoides have been
      reported. A 75-year-old woman presenting with multiple ill-defined areas of
      marked cutaneous wrinkling on the trunk and extremities is reported.
      Histopathological examination showed characteristic features of mycosis fungoides
      along with an interstitial dermal infiltrate composed predominantly of atypical
      lymphocytes with histiocytes intermingled within the collagen bundles. A focal
      reduction and fragmentation of elastic fibers was demonstrated. This observation
      illustrates a peculiar and previously unreported clinicopathological presentation
      of mycosis fungoides: cutis laxa-like mycosis fungoides, expanding the spectrum
      of mycosis fungoides variants associated with abnormalities of the dermal elastic
      fibers.

PMID- 22409398
TI  - Improvement of isolated rat pancreatic islets function by combination of cerium
      oxide nanoparticles/sodium selenite through reduction of oxidative stress.
AB  - Insulin Dependent Diabetes Mellitus (IDDM) is a disease with high incidence with
      no pure cure therapy yet. In most of cases, these patients need pancreatic islets
      transplantation that is not completely successful because of oxidative stress
      happening during isolation and transplantation procedures. In the present study,
      effective factors in transplantation procedure such as viability, insulin
      secretion, production of reactive oxygen molecules (ROM), and mitochondrial
      energy as ATP/ADP ratio were examined in the isolated islets exposed to sodium
      selenite (Na2SeO3; 0 30 nmol/L), metal form of cerium oxide (100 nm), cerium
      oxide nanoparticles (100 nm) and combination of Na2SeO3 (30 nmol/L)/cerium oxide
      nanoparticles (100 nm) in a time course (1, 2, 4 and 6 days posttreatment)
      manner. The results showed a significant increase of cells viability, secretion
      of insulin, and ATP/ADP ratio and a reduction in ROM by use of sodium selenite,
      cerium oxide nanoparticles, and especially combination of cerium oxide
      nanoparticles/sodium selenite. Interestingly, not only no improvement was found
      with metal form of cerium oxide but also deterioration occurred in tested
      markers. Results suggest that pretreatment with combination of cerium oxide
      nanoparticles/sodium selenite can improve transplantation outcome and graft
      function by control of oxidative stress damage.

PMID- 22409397
TI  - What influences the use of dental services by adults in the UK?
AB  - OBJECTIVES: Optimizing access to and utilization of dental services remains a
      major public health challenge. The aim of this study was to use Andersen's
      behavioural model to investigate the factors that influence utilization of dental
      services and predict oral health outcomes, and to identify how access could be
      improved. METHODS: Secondary analysis was conducted of data from a regional
      postal survey (n = 10 864) of adults in the UK. Items were chosen to reflect
      variables of Andersen's behavioural model including predisposing characteristics
      (deprivation), enabling resources (perceived difficulty accessing a dentist),
      need (perceived treatment need), health behaviours (reason for attendance and
      time since the last visit to the dentist) and oral health outcomes (oral health
      impacts (symptoms, functional limitation and social) and global oral health).
      Structural equation modelling was used to estimate the direct and indirect
      pathways between the variables within the model. RESULTS: When a combination of
      indirect and direct effects were taken into account, perceived difficulty
      accessing the dentist was associated with higher perceived treatment need (beta =
      0.25, P < 0.01), increased oral health impacts (beta = -0.23, P < 0.01) and worse
      global oral health (beta = -0.21, P < 0.01). Overall, the variables included
      within this model explained 17.4% of the variance for dental attendance, 55.4% of
      the variance for the length of time since people had last visited the dentist,
      21.7% of the variance for oral health impacts and 42.9% of the variance for
      people's global oral health. CONCLUSIONS: Perceived treatment need and difficulty
      accessing dental services were found to be key predictors of oral health
      outcomes. Further research is needed to develop and evaluate effective
      interventions to improve access to dental services.

PMID- 22409399
TI  - Probing the effects of DNA-protein interactions on DNA hole transport: the N
      terminal histone tails modulate the distribution of oxidative damage and chemical
      lesions in the nucleosome core particle.
AB  - The ability of DNA to transport positive charges, or holes, over long distances
      is well-established, but the mechanistic details of how this process is
      influenced by packaging into DNA-protein complexes have not been fully
      delineated. In eukaryotes, genomic DNA is packaged into chromatin through its
      association with the core histone octamer to form the nucleosome core particle
      (NCP), a complex whose structure can be modulated through changes in the local
      environment and the histone proteins. Because (i) varying the salt concentration
      and removing the histone tails influence the structure of the NCP in known ways
      and (ii) previous studies have shown that DNA hole transport (HT) occurs in the
      nucleosome, we have used our previously described 601 sequence NCPs to test the
      hypothesis that DNA HT dynamics can be modulated by structural changes in a DNA
      protein complex. We show that at low salt concentrations there is a sharp
      increase in long-range DNA HT efficiency in the NCP as compared to naked DNA.
      This enhancement of HT can be negated by either removal of the histone tails at
      low salt concentrations or disruption of the interaction of the packaged DNA and
      the histone tails by increasing the buffer's ionic strength. Association of the
      histone tails with 601 DNA at low salt concentrations shifts the guanine damage
      spectrum to favor lesions like 8-oxoguanine in the NCP, most likely through
      modulation of the rate of the reaction of the guanine radical cation with oxygen.
      These experimental results indicate that for most genomic DNA, the influence of
      DNA-protein interactions on DNA HT will depend strongly on the level of
      protection of the DNA nucleobases from oxygen. Further, these results suggest
      that the oxidative damage arising from DNA HT may vary in different genomic
      regions depending on the presence of either euchromatin or heterochromatin.

PMID- 22409401
TI  - Frequency of urinary tract infection in dogs with inflammatory skin disorders
      treated with ciclosporin alone or in combination with glucocorticoid therapy: a
      retrospective study.
AB  - BACKGROUND: Few studies have investigated the frequency of urinary tract
      infection (UTI) in dogs receiving long-term ciclosporin therapy.
      HYPOTHESIS/OBJECTIVES: The goal of the study was to investigate the frequency of
      UTI in dogs receiving ciclosporin with or without glucocorticoids. A secondary
      goal was to determine whether bacteriuria, pyuria and urine specific gravity were
      good predictors of UTI, and if ciclosporin dose, concurrent ketoconazole therapy,
      sex or duration of therapy affected the frequency of UTI. Animals -  Eighty-seven
      dogs with various inflammatory skin disorders and 59 control dogs with
      inflammatory skin conditions that had not received glucocorticoids or ciclosporin
      for 6 months were enrolled. METHODS: This study was retrospective. The first
      urine culture from dogs receiving ciclosporin was compared with control dogs
      using Fisher's exact test. A logistic mixed model was used to test for
      association between a positive bacterial culture and duration of treatment, dose
      of ciclosporin, concurrent ketoconazole therapy and sex. The sensitivities and
      specificities for bacteriuria, pyuria and urine specific gravity were determined.
      RESULTS: Twenty-six of 87 (30%) ciclosporin-treated dogs had at least one
      positive culture. Compared with 3% positive control samples, 15% were positive in
      treated dogs (P=0.027). The sensitivity and specificity were, respectively, 64.1
      and 98.1% for bacteriuria, 74.4 and 70.9% for pyuria, and 56.4 and 65.3% for
      urine specific gravity. All other analysed parameters were not significantly
      different. CONCLUSIONS AND CLINICAL IMPORTANCE: The results suggest that routine
      urine cultures and assessment of bacteriuria by cystocentesis should be part of
      the monitoring for dogs on long-term ciclosporin with and without
      glucocorticoids.

PMID- 22409400
TI  - Gem1 and ERMES do not directly affect phosphatidylserine transport from ER to
      mitochondria or mitochondrial inheritance.
AB  - In yeast, a protein complex termed the ER-Mitochondria Encounter Structure
      (ERMES) tethers mitochondria to the endoplasmic reticulum. ERMES proteins are
      implicated in a variety of cellular functions including phospholipid synthesis,
      mitochondrial protein import, mitochondrial attachment to actin, polarized
      mitochondrial movement into daughter cells during division, and maintenance of
      mitochondrial DNA (mtDNA). The mitochondrial-anchored Gem1 GTPase has been
      proposed to regulate ERMES functions. Here, we show that ERMES and Gem1 have no
      direct role in the transport of phosphatidylserine (PS) from the ER to
      mitochondria during the synthesis of phosphatidylethanolamine (PE), as PS to PE
      conversion is not affected in ERMES or gem1 mutants. In addition, we report that
      mitochondrial inheritance defects in ERMES mutants are a secondary consequence of
      mitochondrial morphology defects, arguing against a primary role for ERMES in
      mitochondrial association with actin and mitochondrial movement. Finally, we show
      that ERMES complexes are long-lived, and do not depend on the presence of Gem1.
      Our findings suggest that the ERMES complex may have primarily a structural role
      in maintaining mitochondrial morphology.

PMID- 22409402
TI  - Photocytotoxicity and magnetic relaxivity responses of dual-porous gamma
      Fe2O3@meso-SiO2 microspheres.
AB  - Novel high magnetization microspheres with porous gamma-Fe(2)O(3) core and porous
      SiO(2) shell were synthesized using a templating method, whereas the size of the
      magnetic core and the thickness of the porous shell can be controlled by tuning
      the experimental parameters. By way of an example, as-prepared gamma
      Fe(2)O(3)@meso-SiO(2) microspheres (170 nm) display excellent water-dispersity
      and show photonic characteristics under externally applied a magnetic field. The
      magnetic property of the gamma-Fe(2)O(3) porous core enables the microspheres to
      be used as a contrast agent in magnetic resonance imaging with a high r(2) (76.5
      s(-1) mM(-1) Fe) relaxivity. The biocompatible composites possess a large BET
      surface area (222.3 m(2)/g), demonstrating that they can be used as a
      bifunctional agent for both MRI and drug carrier. Because of the high substrate
      loading of the magnetic, dual-porous materials, only a low dosage of the
      substrate will be acquired for potential practical applications. Hydrophobic
      zinc(II) phthalocyanine (ZnPC) photosensitizing molecules have been encapsulated
      into the dual-porous microspheres to form gamma-Fe(2)O(3)@meso-SiO(2)-ZnPC
      microspheres. Biosafety, cellular uptake in HT29 cells, and in vitro MRI of these
      nanoparticles have been demonstrated. Photocytotoxicity (lambda > 610 nm) of the
      HT29 cells uptaken with gamma-Fe(2)O(3)@meso-SiO(2)-ZnPC microspheres has been
      demonstrated for 20 min illumination.

PMID- 22409403
TI  - Effect of sample preparation on the measurement of sugars, organic acids, and
      polyphenols in apple fruit by mid-infrared spectroscopy.
AB  - The objectives of this study were (i) to test different conditions of freezing,
      thawing, and grinding during sample preparation and (ii) to evaluate the
      possibility of using mid-infrared spectroscopy for analyzing the composition of
      sugars, organic acids, and polyphenols in apples. Seven commercial apple
      cultivars were chosen for their large variability in composition (total
      polyphenols from 406 to 1033 mg kg(-1) fresh weight). The different conditions of
      sample preparation affected only the phenolic compounds and not sugars or organic
      acids. The regression models of the mid-infrared spectra showed a good ability to
      estimate sugar and organic acid contents (R(2) >= 0.96), except for citric acid.
      Good predictions were obtained for total phenolic, flavan-3-ols, and procyanidins
      (R(2) >= 0.94) provided oxidation was avoided during sample preparation. A rapid
      and simple procedure was then proposed for phenolic compounds using sodium
      fluoride during sample homogenization at ambient temperature and freeze-drying
      before spectra acquisition.

PMID- 22409404
TI  - Palladium-catalyzed amination of chloromethylnaphthalene and
      chloromethylanthracene derivatives with various amines.
AB  - Palladium-catalyzed amination of chloromethylnaphthalene and
      chloromethylanthracene derivatives to produce naphthylamines and anthrylamines in
      satisfactory to good yields has been developed. The unprecedented amination
      reactions proceeded smoothly under mild conditions in the presence of
      Pd(PPh(3))(4) as a catalyst.

PMID- 22409405
TI  - Spinal cysticercosis mimicking a tumor in a pediatric patient.
AB  - Parasitic infections of the central nervous system (CNS) occur mostly in
      underdeveloped regions of the world. Neurocysticercosis (NC) occurs when the
      larval form of the T. solium tapeworm invades the CNS. Spinal cysticercosis is an
      extremely rare type of NC and occurs when the cyst occupies the subarachnoid
      space of the spinal column. Previous cases have been successfully treated through
      both surgical and medical means. The current case describes the symptoms,
      diagnosis, and treatment of a patient with this extremely uncommon manifestation
      of neurocysticercosis.

PMID- 22409406
TI  - Splenic cysts in the pediatric population: a report of 21 cases with review of
      the literature.
AB  - Splenic cysts are rare lesions that can occur in parasitic and non-parasitic
      forms. Because they are uncommon, the classification, pathogenesis, and
      management techniques are still debated. The continual review of splenic cyst
      cases in the pediatric population is essential for establishing a clear diagnosis
      and course of treatment. This report presents 21 cases of pediatric splenic cysts
      observed at Children's Healthcare of Atlanta over an 18 year period (1993-2011).
      The cases include both parasitic and and nonparasitic cysts. The current splenic
      cyst classification and treatment methods are analyzed through a review of the
      current theories and based on our experiences.

PMID- 22409407
TI  - Revisiting the histopathologic spectrum of congenital pulmonary developmental
      disorders.
AB  - A retrospective analysis of lobectomy, pneumonectomy, cystectomy specimens (10
      years) and stillbirth/neonatal autopsies (5 years) was carried out to analyze the
      histologic spectrum of congenital pulmonary developmental
      disorders/malformations. The autopsy data was analyzed to identify the lesions
      that are more diffuse and not amenable to surgical management. A total of 166
      cases of pulmonary developmental disorders/ malformation were found. Out of 2,155
      stillbirth/neonatal autopsies, there were 105 cases of pulmonary hypoplasia, 2
      cases of congenital pulmonary lymphangiectasis, 2 cases of extralobar
      sequestration, and 3 cases of congenital pulmonary airway malformation (CPAM).
      Among the surgical specimens, there were 21 cases of CPAM, 11 cases of intralobar
      sequestration, 5 cases of congenital lobar emphysema and 17 cases of bronchogenic
      cyst. All these malformations have been described in reference to the latest
      updated classification of developmental disorders/malformations.

PMID- 22409408
TI  - Commonest overgrowth syndromes.
AB  - Overgrowth syndromes, although rare, are diagnosed more frequently lately. Major
      progress, such as the identification of genetic causes, has recently enhanced the
      delineation of the characteristic and noncharacteristic manifestations, phenotype
      genotype correlations and knowledge of the underlying pathophysiologic
      mechanisms. This review provides a summary of the most important overgrowth
      syndromes aiming to familiarize the treating physician with the cardinal clinical
      features involved in these syndromes that encompass overgrowth, but also have a
      variety of other clinical manifestations (neurologic, musculoskeletal, skin, and
      accompanying tumors).

PMID- 22409410
TI  - Power tools for Alzheimer's disease - an electrochemical preamp for Abeta.

PMID- 22409412
TI  - Bright light and early darkness, reflections on the life of Tiziano Baccetti: an
      appreciation.

PMID- 22409411
TI  - Pseudoscorpion mitochondria show rearranged genes and genome-wide reductions of
      RNA gene sizes and inferred structures, yet typical nucleotide composition bias.
AB  - BACKGROUND: Pseudoscorpions are chelicerates and have historically been viewed as
      being most closely related to solifuges, harvestmen, and scorpions. No
      mitochondrial genomes of pseudoscorpions have been published, but the
      mitochondrial genomes of some lineages of Chelicerata possess unusual features,
      including short rRNA genes and tRNA genes that lack sequence to encode arms of
      the canonical cloverleaf-shaped tRNA. Additionally, some chelicerates possess an
      atypical guanine-thymine nucleotide bias on the major coding strand of their
      mitochondrial genomes. RESULTS: We sequenced the mitochondrial genomes of two
      divergent taxa from the chelicerate order Pseudoscorpiones. We find that these
      genomes possess unusually short tRNA genes that do not encode cloverleaf-shaped
      tRNA structures. Indeed, in one genome, all 22 tRNA genes lack sequence to encode
      canonical cloverleaf structures. We also find that the large ribosomal RNA genes
      are substantially shorter than those of most arthropods. We inferred secondary
      structures of the LSU rRNAs from both pseudoscorpions, and find that they have
      lost multiple helices. Based on comparisons with the crystal structure of the
      bacterial ribosome, two of these helices were likely contact points with tRNA T
      arms or D-arms as they pass through the ribosome during protein synthesis.The
      mitochondrial gene arrangements of both pseudoscorpions differ from the ancestral
      chelicerate gene arrangement. One genome is rearranged with respect to the
      location of protein-coding genes, the small rRNA gene, and at least 8 tRNA genes.
      The other genome contains 6 tRNA genes in novel locations. Most chelicerates with
      rearranged mitochondrial genes show a genome-wide reversal of the CA nucleotide
      bias typical for arthropods on their major coding strand, and instead possess a
      GT bias. Yet despite their extensive rearrangement, these pseudoscorpion
      mitochondrial genomes possess a CA bias on the major coding strand. Phylogenetic
      analyses of all 13 mitochondrial protein-coding gene sequences consistently yield
      trees that place pseudoscorpions as sister to acariform mites. CONCLUSION: The
      well-supported phylogenetic placement of pseudoscorpions as sister to Acariformes
      differs from some previous analyses based on morphology. However, these two
      lineages share multiple molecular evolutionary traits, including substantial
      mitochondrial genome rearrangements, extensive nucleotide substitution, and loss
      of helices in their inferred tRNA and rRNA structures.

PMID- 22409413
TI  - Re: Nasal obstruction causes a decrease in lip-closing force. Angle Orthod.
      2011;81:750-753, by Sabashi K, Washino K, Saitoh I, Yamasaki Y, Kawabata A, Mukai
      Y, Kitai N.

PMID- 22409415
TI  - Yoshiki and KS222.

PMID- 22409416
TI  - New guidelines for treatment of avulsed permanent teeth.

PMID- 22409417
TI  - International Association of Dental Traumatology guidelines for the management of
      traumatic dental injuries: 2. Avulsion of permanent teeth.
AB  - Avulsion of permanent teeth is one of the most serious dental injuries, and a
      prompt and correct emergency management is very important for the prognosis. The
      International Association of Dental Traumatology (IADT) has developed a consensus
      statement after a review of the dental literature and group discussions.
      Experienced researchers and clinicians from various specialties were included in
      the task group. The guidelines represent the current best evidence and practice
      based on literature research and professionals' opinion. In cases where the data
      did not appear conclusive, recommendations were based on the consensus opinion or
      majority decision of the task group. Finally, the IADT board members were giving
      their opinion and approval. The primary goal of these guidelines is to delineate
      an approach for the immediate or urgent care of avulsed permanent teeth.

PMID- 22409418
TI  - Meta-analysis on the comparison between two topical calcineurin inhibitors in
      atopic dermatitis.
AB  - Topical calcineurin inhibitors have proved to be suitable for the treatment of
      AD. We conducted a meta-analysis comparing efficacy and tolerance of tacrolimus
      with pimecrolimus in treatment of AD. According to our meta-analysis, tacrolimus
      0.1% was more effective than pimecrolimus 1% in adult patients (week 3: risk
      ratio [RR] 0.55, 95% confidence interval [CI] 0.42-0.73), and tacrolimus (a
      combination of 0.03% and 0.1%) was also more effective than pimecrolimus 1% in
      pediatric patients (week 6/end of study: RR 0.76, 95% CI 0.63-0.92). Regardless
      of age or illness severity, tacrolimus 0.1% had higher efficacy than pimecrolimus
      1% in the treatment of AD (week 3: RR 0.55, 95% CI 0.42-0.72). In adult patients,
      tacrolimus 0.1% had more adverse events than pimecrolimus 1% (RR 1.30, 95% CI
      1.02-1.66), but the incidence of adverse events between tacrolimus 0.1% (or
      0.03%) and pimecrolimus 1% was not significantly different in pediatric patients.
      No matter whether the patients were adult or pediatric, more pimecrolimus-treated
      patients withdrew from the trials because of a lack of efficacy. Regardless of
      age and illness severity, more pimecrolimus 1%-treated patients withdrew from the
      trials because of a lack of efficacy, compared with tacrolimus 0.1% (or 0.03%)
      treated patients. More pimecrolimus-treated pediatric patients withdrew from the
      trials because of adverse events (RR 0.26, 95% CI 0.1-0.68). More pimecrolimus 1%
      treated patients withdrew from the trials because of adverse events, compared
      with tacrolimus 0.03%-treated patients, regardless of age (RR 0.1, 95% CI 0.02
      0.53). In conclusion, tacrolimus ointment has higher efficacy and better
      tolerance than pimecrolimus cream in treatment of AD.

PMID- 22409419
TI  - Near-infrared imaging of veins in facial injection of botulinum toxin and
      hyaluronic acid.

PMID- 22409420
TI  - p-Type polymer-hybridized high-performance piezoelectric nanogenerators.
AB  - Enhancing the output power of a nanogenerator is essential in applications as a
      sustainable power source for wireless sensors and microelectronics. We report
      here a novel approach that greatly enhances piezoelectric power generation by
      introducing a p-type polymer layer on a piezoelectric semiconducting thin film.
      Holes at the film surface greatly reduce the piezoelectric potential screening
      effect caused by free electrons in a piezoelectric semiconducting material.
      Furthermore, additional carriers from a conducting polymer and a shift in the
      Fermi level help in increasing the power output. Poly(3-hexylthiophene) (P3HT)
      was used as a p-type polymer on piezoelectric semiconducting zinc oxide (ZnO)
      thin film, and phenyl-C(61)-butyric acid methyl ester (PCBM) was added to P3HT to
      improve carrier transport. The ZnO/P3HT:PCBM-assembled piezoelectric power
      generator demonstrated 18-fold enhancement in the output voltage and tripled the
      current, relative to a power generator with ZnO only at a strain of 0.068%. The
      overall output power density exceeded 0.88 W/cm(3), and the average power
      conversion efficiency was up to 18%. This high power generation enabled red,
      green, and blue light-emitting diodes to turn on after only tens of times bending
      the generator. This approach offers a breakthrough in realizing a high
      performance flexible piezoelectric energy harvester for self-powered electronics.

PMID- 22409421
TI  - Caution is warranted in interpreting data from a recent trial of modified
      constraint-induced therapy.

PMID- 22409422
TI  - Monodisperse lanthanide fluoride nanocrystals: synthesis and luminescent
      properties.
AB  - Three types of high-quality, monodisperse lanthanide fluoride colloidal
      nanocrystals (NCs) including LnF(3) (Ln = La-Pr), NaLnF(4) (Ln = Sm-Er), and
      Na(5)Ln(9)F(32) (Ln = Tm-Lu) with two crystal phases (hexagonal and cubic) and a
      rich variety of morphologies have been synthesized in high boiling organic
      solvents oleic acid and 1-octadecene, via a thermal decomposition pathway. The as
      synthesized NCs were well characterized by X-ray diffraction (XRD), transmission
      electron microscopy (TEM), high resolution transmission electron microscopy
      (HRTEM), Fourier transform infrared spectroscopy (FT-IR), and photoluminescence
      (PL) spectra, respectively. It is found that the as-synthesized NCs consist of
      monodisperse nanoparticles with diverse shapes and narrow size distribution,
      which can easily disperse in nonpolar cyclohexane solvent. Additionally, a
      possible mechanism of NC nucleation and growth has been proposed. The results
      reveal that the formation of monodisperse NCs closely correlates with the
      inherent nature of lanthanide series from La to Lu. Under 980 nm NIR excitation,
      as-synthesized Yb(3+)/Ln(3+) (Ln = Er, Tm, Ho)-doped NaGdF(4) and Na(5)Lu(9)F(32)
      colloidal NCs show the respective characteristic up-conversion (UC) emissions of
      Er(3+), Tm(3+), and Ho(3+), which are promising for applications in biolabels,
      bioimaging, displays, and other optical technologies.

PMID- 22409423
TI  - Acellular dermal matrix graft with or without enamel matrix derivative for root
      coverage in smokers: a randomized clinical study.
AB  - AIM: The aim of this randomized controlled clinical study was to compare the use
      of an acellular dermal matrix graft (ADMG) with or without the enamel matrix
      derivative (EMD) in smokers to evaluate which procedure would provide better root
      coverage. MATERIAL AND METHODS: Nineteen smokers with bilateral Miller Class I or
      II gingival recessions >=3 mm were selected. The test group was treated with an
      association of ADMG and EMD, and the control group with ADMG alone. Probing
      depth, relative clinical attachment level, gingival recession height, gingival
      recession width, keratinized tissue width and keratinized tissue thickness were
      evaluated before the surgeries and after 6 months. Wilcoxon test was used for the
      statistical analysis at significance level of 5%. RESULTS: No significant
      differences were found between groups in all parameters at baseline. The mean
      gain recession height between baseline and 6 months and the complete root
      coverage favored the test group (p = 0.042, p = 0.019 respectively). CONCLUSION:
      Smoking may negatively affect the results achieved through periodontal plastic
      procedures; however, the association of ADMG and EMD is beneficial in the root
      coverage of gingival recessions in smokers, 6 months after the surgery.

PMID- 22409424
TI  - Community scale 15N isoscapes: tracing the spatial impact of an exotic N2 -fixing
      invader.
AB  - Plant-plant interactions are key processes shaping plant communities, but methods
      are lacking to accurately capture the spatial dimension of these processes.
      Isoscapes, i.e. spatially continuous observations of variations in stable isotope
      ratios, provide innovative methods to trace the spatial dimension of ecological
      processes at continental to global scales. Herein, we test the usefulness of
      nitrogen isoscapes (delta(15) N) for quantifying alterations in community
      functioning following exotic plant invasion. Nitrogen introduced by an exotic
      N(2) -fixing acacia could be accurately traced through the ecosystem and into the
      surrounding native vegetation by combining native species foliar delta(15) N with
      spatial information regarding plant location using geostatistical methods. The
      area impacted by N-addition was at least 3.5-fold greater than the physical area
      covered by the invader. Thus, downscaling isoscapes to the community level opens
      new frontiers in quantifying the spatial dimension of functional changes
      associated with invasion and in resolving the spatial component of within
      community interactions.

PMID- 22409425
TI  - Matrix metalloprotease 2-responsive multifunctional liposomal nanocarrier for
      enhanced tumor targeting.
AB  - A novel "smart" multifunctional drug delivery system was successfully developed
      to respond to the up-regulated matrix metalloprotease 2 (MMP2) in the tumor
      microenvironment and improve cancer cell-specific delivery of loaded drugs. The
      system represents a surface-functionalized liposomal nanocarrier, for which two
      functional polyethylene glycol (PEG)-lipid conjugates were synthesized and
      characterized. The functionalized liposome was further modified with the tumor
      cell-specific antinucleosome monoclonal antibody (mAb 2C5). In the resulting
      system, several drug delivery strategies were combined in the same nanocarrier in
      a simple way and coordinated in an optimal fashion. The functions of the
      nanocarrier include (i) the hydrophilic and flexible long PEG chains to prevent
      nanocarrier nonspecific interactions and prolong its circulation time; (ii) a
      nanoscale size of the system that allows for its passive tumor targeting via the
      enhanced permeability and retention (EPR) effect; (iii) a mAb 2C5 to allow for
      the specific targeting of tumor cells; (iv) a matrix metalloprotease 2-sensitive
      bond between PEG and lipid that undergoes cleavage in the tumor by the highly
      expressed extracellular MMP2 for the removal of PEG chains; (v) cell-penetrating
      peptide (TATp) triggering of the enhanced intracellular delivery of the system
      after long-chain PEG removal and exposure of the previously hidden surface
      attached TATp. It is shown that such a design can enhance the targetability and
      internalization of nanocarriers in cancer cells.

PMID- 22409426
TI  - Hepatoprotective activity of methanolic extract of Hiptage bengalensis leaves
      against CCl4-induced hepatotoxicity in rats.
AB  - The objective of the present study was to evaluate hepatoprotective activity of
      methanolic extract of Hiptage bengalensis (L.) kurz (MEHB) in rats. Hepatic
      damage was induced by administration of carbontetrachloride(1 ml/kg, b.w, p.o.)
      in combination with liquid paraffin (1:1) as a single dose on 7th day. The extent
      of liver damage was studied by estimating biochemical parameters. Administration
      of MEHB (200 mg & 400 mg/kg) for 6 days before carbontetrachloride administration
      showed a significant reduction (p < 0.01) of serum liver damage enzymes markers
      aspartate transaminase, alanine transaminase, total bilirubin and alkaline
      phosphatase (ALP). Histopathological changes of hepatic tissue were also
      evaluated in control and MEHB treated groups. Results also indicated that MEHB
      possessed potential antioxidant effect by increasing the levels of glutathione
      and also possessed free radical scavenging activities. The hepatoprotective
      effect of Hiptage bengalensis (L.) kurz was comparable to standard drug silymarin
      (50 mg/kg).

PMID- 22409427
TI  - Identification of exosite residues of factor Xa involved in recognition of PAR-2
      on endothelial cells.
AB  - Recent results have indicated that factor Xa (FXa) cleaves protease-activated
      receptor 2 (PAR-2) to elicit protective intracellular signaling responses in
      endothelial cells. In this study, we investigated the molecular determinants of
      the specificity of FXa interaction with PAR-2 by monitoring the cleavage of PAR-2
      by FXa in endothelial cells transiently transfected with a PAR-2 cleavage
      reporter construct in which the extracellular domain of the receptor was fused to
      cDNA encoding for alkaline phosphatase. Comparison of the cleavage efficiency of
      PAR-2 by a series of FXa mutants containing mutations in different surface loops
      indicated that the acidic residues of 39-loop (Glu-36, Glu-37, and Glu-39) and
      the basic residues of 60-loop (Lys-62 and Arg-63), 148-loop (Arg-143, Arg-150,
      and Arg-154), and 162-helix (Arg-165 and Lys-169) contribute to the specificity
      of receptor recognition by FXa on endothelial cells. This was evidenced by
      significantly reduced activity of mutants toward PAR-2 expressed on transfected
      cells. The extent of loss in the PAR-2 cleavage activity of FXa mutants
      correlated with the extent of loss in their PAR-2-dependent intracellular
      signaling activity. Further characterization of FXa mutants indicated that, with
      the exception of basic residues of 162-helix, which play a role in the
      recognition specificity of the prothrombinase complex, none of the surface loop
      residues under study makes a significant contribution to the activity of FXa in
      the prothrombinase complex. These results provide new insight into mechanisms
      through which FXa specifically interacts with its macromolecular substrates in
      the clotting and signaling pathways.

PMID- 22409428
TI  - Efficient, chemoenzymatic process for manufacture of the Boceprevir bicyclic
      [3.1.0]proline intermediate based on amine oxidase-catalyzed desymmetrization.
AB  - The key structural feature in Boceprevir, Merck's new drug treatment for
      hepatitis C, is the bicyclic [3.1.0]proline moiety "P2". During the discovery and
      development stages, the P2 fragment was produced by a classical resolution
      approach. As the drug candidate advanced through clinical trials and approached
      regulatory approval and commercialization, Codexis and Schering-Plough (now
      Merck) jointly developed a chemoenzymatic asymmetric synthesis of P2 where the
      net reaction was an oxidative Strecker reaction. The key part of this reaction
      sequence is an enzymatic oxidative desymmetrization of the prochiral amine
      substrate.

PMID- 22409429
TI  - Facile fabrication of gold nanoparticles-poly(vinyl alcohol) electrospun water
      stable nanofibrous mats: efficient substrate materials for biosensors.
AB  - Electrospun nanofibrous mats are intensively studied as efficient scaffold
      materials applied in the fields of tissue engineering, catalysis, and biosensors
      due to their flexibility and porosity. In this paper, we report a facile route to
      fabricate gold nanoparticles-poly(vinyl alcohol) (Au NPs-PVA) hybrid water stable
      nanofibrous mats with tunable densities of Au NPs and further demonstrate the
      potential application of as-prepared Au NPs-PVA nanofibrous mats as efficient
      biosensor substrate materials. First, through the designed in situ cross-linkage
      in coelectrospun PVA-glutaraldehyde nanofibers, water insoluble PVA nanofibrous
      mats with suitable tensile strength were successfully prepared. Then, 3
      mercaptopropyltrimethoxysilane (MPTES) was modified on the surface of obtained
      PVA nanofibrous films, which triggered successful homogeneous decoration of Au
      NPs through gold-sulfur bonding interactions. Finally, the Au NPs-PVA nanofibrous
      mats embedded with horseradish peroxidase (HRP) by electrostatic interactions
      were used as biosensor substrate materials for H(2)O(2) detection. The fabricated
      HRP-Au NPs/PVA biosensor showed a highly sensitive detection of H(2)O(2) with a
      detection limit of 0.5 MUM at a signal-to-noise ratio of 3. By modifying other
      different functional nanaoparticles or enzyme on the PVA nanofibrous film will
      further expand their potential applications as substrate materials of different
      biosensors.

PMID- 22409431
TI  - A personal recollection of Yoshiki Hotta as a mentor.

PMID- 22409430
TI  - The evolution of cardiolipin biosynthesis and maturation pathways and its
      implications for the evolution of eukaryotes.
AB  - BACKGROUND: Cardiolipin (CL) is an important component in mitochondrial inner and
      bacterial membranes. Its appearance in these two biomembranes has been considered
      as evidence of the endosymbiotic origin of mitochondria. But CL was reported to
      be synthesized through two distinct enzymes--CLS_cap and CLS_pld in eukaryotes
      and bacteria. Therefore, how the CL biosynthesis pathway evolved is an
      interesting question. RESULTS: Phylogenetic distribution investigation of CL
      synthase (CLS) showed: most bacteria have CLS_pld pathway, but in partial
      bacteria including proteobacteria and actinobacteria CLS_cap pathway has already
      appeared; in eukaryotes, Supergroup Opisthokonta and Archaeplastida, and Subgroup
      Stramenopiles, which all contain multicellular organisms, possess CLS_cap
      pathway, while Supergroup Amoebozoa and Excavata and Subgroup Alveolata, which
      all consist exclusively of unicellular eukaryotes, bear CLS_pld pathway;
      amitochondriate protists in any supergroups have neither. Phylogenetic analysis
      indicated the CLS_cap in eukaryotes have the closest relationship with those of
      alpha proteobacteria, while the CLS_pld in eukaryotes share a common ancestor but
      have no close correlation with those of any particular bacteria. CONCLUSIONS: The
      first eukaryote common ancestor (FECA) inherited the CLS_pld from its bacterial
      ancestor (e. g. the bacterial partner according to any of the hypotheses about
      eukaryote evolution); later, when the FECA evolved into the last eukaryote common
      ancestor (LECA), the endosymbiotic mitochondria (alpha proteobacteria) brought in
      CLS_cap, and then in some LECA individuals the CLS_cap substituted the CLS_pld,
      and these LECAs would evolve into the protist lineages from which multicellular
      eukaryotes could arise, while in the other LECAs the CLS_pld was retained and the
      CLS_cap was lost, and these LECAs would evolve into the protist lineages
      possessing CLS_pld. Besides, our work indicated CL maturation pathway arose after
      the emergence of eukaryotes probably through mechanisms such as duplication of
      other genes, and gene duplication and loss occurred frequently at different
      lineage levels, increasing the pathway diversity probably to fit the complicated
      cellular process in various cells. Our work also implies the classification
      putting Stramenopiles and Alveolata together to form Chromalveolata may be
      unreasonable; the absence of CL synthesis and maturation pathways in
      amitochondriate protists is most probably due to secondary loss.

PMID- 22409432
TI  - Health during pregnancy and beyond: Fetal trophoblast cells as chief co
      ordinators of intrauterine growth and reproductive success.
AB  - Abstract   Differentiation of extra-embryonic tissues and organs, notably the
      placenta, is vital for embryonic development and growth throughout gestation,
      starting from a few days after fertilization when the trophoblast cell lineage
      arises until parturition. In utero metabolic programming events may even extend
      the impact of placental function well into adulthood as they may predispose the
      offspring to common pathologies such as diabetes and cardiovascular disease. This
      review summarizes key steps that lead up to formation of a functional placenta.
      It highlights recent insights that have advanced our view of how early
      trophoblast expansion is achieved and how sufficient maternal blood supply to the
      developing fetus is secured. Exciting cumulative data have revealed the
      importance of a close cross-talk between the embryo proper and extra-embryonic
      trophoblast cells that involves extracellular matrix components in the
      establishment of a stem cell-like niche and proliferation compartment.
      Remarkably, placental function also relies on beneficial interactions between
      trophoblast cells and maternal immune cells at the implantation site. Our growing
      knowledge of the molecular mechanisms involved in trophoblast differentiation and
      function will help to devise informed approaches aimed at deciphering how
      placentation is controlled in humans as an essential process for reproductive
      success and long-term health.

PMID- 22409433
TI  - Induced systemic resistance in Arabidopsis thaliana against Pseudomonas syringae
      pv. tomato by 2,4-diacetylphloroglucinol-producing Pseudomonas fluorescens.
AB  - Pseudomonas fluorescens strains that produce the polyketide antibiotic 2,4
      diacetylphloroglucinol (2,4-DAPG) are among the most effective rhizobacteria that
      suppress root and crown rots, wilts, and damping-off diseases of a variety of
      crops, and they play a key role in the natural suppressiveness of some soils to
      certain soilborne pathogens. Root colonization by 2,4-DAPG-producing P.
      fluorescens strains Pf-5 (genotype A), Q2-87 (genotype B), Q8r1-96 (genotype D),
      and HT5-1 (genotype N) produced induced systemic resistance (ISR) in Arabidopsis
      thaliana accession Col-0 against bacterial speck caused by P. syringae pv.
      tomato. The ISR-eliciting activity of the four bacterial genotypes was similar,
      and all genotypes were equivalent in activity to the well-characterized strain P.
      fluorescens WCS417r. The 2,4-DAPG biosynthetic locus consists of the genes phlHGF
      and phlACBDE. phlD or phlBC mutants of Q2-87 (2,4-DAPG minus) were significantly
      reduced in ISR activity, and genetic complementation of the mutants restored ISR
      activity back to wild-type levels. A phlF regulatory mutant (overproducer of 2,4
      DAPG) had ISR activity equivalent to the wild-type Q2-87. Introduction of DAPG
      into soil at concentrations of 10 to 250 MUM 4 days before challenge inoculation
      induced resistance equivalent to or better than the bacteria. Strain Q2-87
      induced resistance on transgenic NahG plants but not on npr1-1, jar1, and etr1
      Arabidopsis mutants. These results indicate that the antibiotic 2,4-DAPG is a
      major determinant of ISR in 2,4-DAPG-producing P. fluorescens, that the genotype
      of the strain does not affect its ISR activity, and that the activity induced by
      these bacteria operates through the ethylene- and jasmonic acid-dependent signal
      transduction pathway.

PMID- 22409434
TI  - Modeling sporulation of Fusicladium carpophilum on nectarine twig lesions:
      relative humidity and temperature effects.
AB  - The production of conidia by Fusicladium carpophilum on twig lesions was
      quantitatively modeled as a function of temperature and duration of high relative
      humidity. During peak sporulation periods in 2007, 2008, and 2009, 1-year-old
      twigs bearing abundant overwintering lesions were removed from a heavily infected
      'Redgold' nectarine orchard, placed in trays at high relative humidity (>95%),
      and incubated at eight constant temperatures for seven durations, resulting in a
      factorial design of 56 treatment combinations. Conidia numbers were estimated
      with a hemacytometer. Results from a six-stage modeling process indicated that,
      at any given temperature, spore production during high relative humidity periods
      increased in a monomolecular- to Gompertz-like pattern. The Richards model, with
      shape parameters of 0.79 to 0.90, was found to provide the best overall fit. When
      the asymptote and rate parameters were derived as functions of temperature using
      Gaussian and quadratic models, respectively, the duration of high relative
      humidity and temperature described 90 to 94% of the variation in conidia
      production. Predictions of the final models were highly correlated with observed
      levels of sporulation (r > 0.94; P < 0.0001), indicating an excellent fit to the
      data. The optimum temperature for sporulation, based on fitting a Gaussian model
      to the maximum sporulation levels at each temperature, was 17.9 to 20.2 degrees
      C, with an overall average of 18.8 degrees C. The derived models give a
      quantitative description of sporulation by F. carpophilum and may have potential
      use in simulators and forecasting systems.

PMID- 22409435
TI  - Prevention of postoperative pulmonary complications through intensive
      preoperative respiratory rehabilitation in patients with esophageal cancer.
AB  - Postoperative pulmonary complications (PPCs) after esophagectomy have been
      reported to occur in 15.9-30% of patients and lead to increased postoperative
      morbidity and mortality, prolonged duration of hospital stay, and additional
      medical costs. The purpose of this retrospective cohort study was to investigate
      the possible prevention of PPCs by intensive preoperative respiratory
      rehabilitation in esophageal cancer patients who underwent esophagectomy. The
      subjects included 100 patients (87 males and 13 females with mean age 66.5 +/-
      8.6 years) who underwent esophagectomy. They were divided into two groups: 63
      patients (53 males and 10 females with mean age 67.4 +/- 9.0 years) in the
      preoperative rehabilitation (PR) group and 37 patients (34 males and 3 females
      with mean age 65.0 +/- 7.8 years) in the non-PR (NPR) group. The PR group
      received sufficient preoperative respiratory rehabilitation for >7 days, and the
      NPR group insufficiently received preoperative respiratory rehabilitation or none
      at all. The results of the logistic regression analysis and multivariate analysis
      to correct for all considerable confounding factors revealed the rates of PPCs of
      6.4% and 24.3% in the PR group and NPR group, respectively. The PR group
      demonstrated a significantly less incidence rate of PPCs than the NPR group (odds
      ratio: 0.14, 95% confidential interval: 0.02~0.64). [Correction added after
      online publication 25 June 2012: confidence interval has been changed from -1.86~
      -0.22] This study showed that the intensive preoperative respiratory
      rehabilitation reduced PPCs in esophageal cancer patients who underwent
      esophagectomy.

PMID- 22409436
TI  - Colorful InAs nanowire arrays: from strong to weak absorption with geometrical
      tuning.
AB  - One-dimensional nanostructure arrays can show fascinatingly different, tunable
      optical response compared to bulk systems. Here we study theoretically and
      demonstrate experimentally how to engineer the reflection and absorption of light
      in epitaxially grown vertical arrays of InAs nanowires (NWs). A striking
      observation is optically visible colors of the array, which we show can be tuned
      depending on the geometrical parameters of the array. Specifically, larger
      diameter NW arrays absorb light more effectively out to a longer wavelength
      compared to smaller diameter arrays. Thus, controlling the diameter provides a
      way to tune the optically observable color of an array. We also find that arrays
      with a larger amount of InAs material reflect less light (or absorb more light)
      than arrays with less material. On the basis of these two trends, InAs NW arrays
      can be designed to absorb light either much more or much less efficiently than a
      thin film of an effective medium containing the same amount of InAs as the NW
      array. The tunable absorption and low area filling factor of the NW arrays
      compared to thin film bode well for III-V photovoltaics and photodetection.

PMID- 22409437
TI  - Cardiovascular and autonomic responses to sexual activity in the rabbit.
AB  - 1. Sexual intercourse is associated with an increased risk of death from
      arrhythmia development, myocardial infarction or stroke. It is unclear whether
      this increased risk is due to physical exertion alone or whether it is an
      inherent aspect of sexual activity itself. 2. Using a telemetric approach, we
      show that sexual activity is associated with transient (8-14 s) but profound
      increases in renal sympathetic nerve activity (RSNA; up to 22-fold that of
      baseline) in both male and female rabbits. This increase was significantly
      greater than that observed during physical exertion (three- to sixfold increase
      in RSNA). 3. In addition, we observed rapid transitions in male rabbits from
      tachycardia (422 +/- 21 b.p.m.; P < 0.01) to bradycardia (186 +/- 28 b.p.m.; P <
      0.05) during and immediately following coitus. This suggests simultaneous
      activation of both the sympathetic and parasympathetic nervous systems. 4. The
      present study provides the first real-time insight into the extreme variation in
      neural and cardiovascular function occurring during sexual activity in normal
      healthy rabbits. Little is known about how the physiological responses to sexual
      activity may change under disease or drug-treatment states, and these findings
      may prove of use to these areas in future.

PMID- 22409438
TI  - Neurovascular disorders in children: a 21st century challenge for paediatric
      neurologists.

PMID- 22409439
TI  - Photochromic metal complexes of N-methyl-4,4'-bipyridinium: mechanism and
      influence of halogen atoms.
AB  - Photochromism of N-methyl-4,4'-bipyridinium (MQ(+)) salts and their metal
      complexes has never been reported. A series of MQ(+) coordinated halozinc
      complexes [(MQ)ZnX(3)] (X = Cl (1), Br (2), I (3)) and
      [(MQ)ZnCl(1.53)I(1.47)](2)(MQ)ZnCl(1.68)I(1.32) (4), with better physicochemical
      stability than halide salts of the MQ(+) cation, have been found to exhibit
      different photochromic behaviors. Compounds 1-3 are isostructural, but only 1 and
      2 show photochromism. Introduction of partial Cl atoms to nonphotochromic
      compound 3 yields compound 4, which also displays photochromism. The photochromic
      response of 1, 2, and 4 indicates the presence of their long-lived charge
      separation states, which originate from X -> MQ(+) electron transfer according to
      ESR and XPS measurements. Studies on the influence of different coordinated
      halogen atoms demonstrate that the Cl atom may be a more suitable electron donor
      than Br and I atoms to design redox photochromic metal complexes.

PMID- 22409440
TI  - Frequency distributions of 174 fractures of the distal condyles of the third
      metacarpal and metatarsal bones in 167 Thoroughbred racehorses (1999-2009).
AB  - REASONS FOR PERFORMING STUDY: Although fractures of the metacarpal and metatarsal
      condyles are the most common long-bone fractures of Thoroughbred horses in
      training, limited data on variations in morphology and incidence have been
      published. Additionally, grouped analyses of previous studies from the UK and USA
      would permit comparison between study groups and the creation of a substantial
      pool of international data. METHODS: Retrospective analysis of case records of
      horses with fractures of the distal condyles of third metacarpal/metatarsal bones
      seen over the last 10 years at Newmarket Equine Hospital. The current series was
      compared with a prior series from the UK; pooled analyses of these, and series
      from the USA were also compared. RESULTS: One hundred and seventy-four fractures
      were identified in 167 racehorses. The current series contained a significantly
      lower proportion of medial condylar fractures than in a similar population 17
      years earlier. Fractures that originated more abaxially tended to be shorter, and
      a significant proportion of lateral condylar fractures arose outside of the
      condylar groove. There was also some apparent seasonality of fractures of the
      lateral condyles in 2-year-old horses, but not so in older horses or those with
      medial condylar fractures. CONCLUSIONS AND POTENTIAL RELEVANCE: A substantial
      portion (approximately 50%) of fractures in the present series cannot be
      explained by unifying theories of aetiopathogenesis, which suggest that fractures
      usually arise within the condylar groove, as a focus of cumulative fatigue and
      failure of adaptation of bone. A separate aetiopathogenesis may be responsible
      for a proportion of condylar fractures encountered in racehorses, and further
      work is required to elucidate this. Changes in the number of medial condylar
      fractures encountered may reflect the introduction of artificial racing and
      training surfaces, and also may reflect changes in the age demographic of horses
      racing in the UK since the introduction of year-round 'all-weather' racing.

PMID- 22409441
TI  - Components of the COPD Assessment Test (CAT) associated with a diagnosis of COPD
      in a random population sample.
AB  - The aim of this study was to determine if components of the COPD Assessment Test
      (CAT), a validated health status impairment instrument, had additional utility in
      identifying patients at risk for COPD in whom spirometry testing is appropriate.
      This study was part of the Canadian Obstructive Lung Disease prevalence study.
      Consenting participants >= 40 years of age were identified by random digit
      dialing. Smoking history, 8-item CAT scores, and post-bronchodilator spirometry
      were recorded for each. Stepwise logistic regression analysis was used to
      identify variables related to the presence of airway obstruction and a final
      logistic model was developed which best predicted COPD in this sample. Of the 801
      individuals approached, 532 were included: 51 (9.6%) had COPD, the majority (92%)
      of whom fit GOLD I or II severity criteria. Items that correlated significantly
      with a COPD diagnosis included the CAT total score (p = 0.01) and its
      breathlessness (p < 0.0001) and phlegm (p = 0.001) components. The final logistic
      model included: age (<55 or >=55 years), smoking status (current, former, never)
      and the CAT breathlessness score (ordinal scale 0-5). The area under the receiver
      operating characteristic curve for this model was 0.77, sensitivity was 77.6%,
      specificity was 64.9% and the positive likelihood ratio was 2.21. In summary, the
      triad of smoking history, age at least 55 years and the presence of exertional
      breathlessness were key elements of a simple model which had reliable measurement
      properties when tested in a random population. This may help identify patients at
      risk for COPD for whom spirometry testing is recommended.

PMID- 22409442
TI  - Insight into the 3D architecture and quasicrystal symmetry of multilayer nanorod
      assemblies from Moire interference patterns.
AB  - Vertical nanorod assembly over three dimensions is shown to result in the
      formation of Moire interference patterns arising from rotational offsets between
      respective monolayer sheets. Six distinct patterns are observed in HRTEM and
      angular dark-field STEM (DF-STEM) images, allowing the exact angle of rotation to
      be determined from their respective size and repeat order. At large rotation
      angles approaching 30 degrees , the aperiodicity in the structure of the nanorod
      supercrystals becomes apparent, resulting in 12-fold ordering characteristics of
      a quasicrystal. The rotational offsets are further elucidated from Fourier
      transform and small angle electron diffraction, allowing interpretation of
      several multilayers when combined with DF-STEM and SEM. Pattern formation owing
      to angular rotation is differentiated from those occurring from a lateral shift,
      providing an important insight into the complex multilayered structures in
      assembled rods that may have an impact on their collective electronic or photonic
      properties. We also show how random tetrapods when present at low concentrations
      in colloidal nanorod solutions act as termination points for 2D sheet
      crystallization, impacting the size and shape of the resultant assemblies. The
      occurrence of Moire patterns in rod assemblies demonstrates the extraordinary
      order achievable in their assembly and offers a nondestructive technique to
      precisely map the placement of each nanorod in this important nanoarchitecture.

PMID- 22409443
TI  - Linking environmental processes to the in situ functioning of microorganisms by
      high-resolution secondary ion mass spectrometry (NanoSIMS) and scanning
      transmission X-ray microscopy (STXM).
AB  - Environmental microbiology research increasingly focuses on the single microbial
      cell as the defining entity that drives environmental processes. The interactions
      of individual microbial cells with each other, the environment and with higher
      organisms shape microbial communities and control the functioning of whole
      ecosystems. A single-cell view of microorganisms in their natural environment
      requires analytical tools that measure both cell function and chemical speciation
      at the submicrometre scale. Here we review the technical capabilities and
      limitations of high-resolution secondary ion mass spectrometry (NanoSIMS) and
      scanning transmission (soft) X-ray microscopy (STXM) and give examples of their
      applications. Whereas NanoSIMS can be combined with isotope-labelling, thereby
      localizing the distribution of cellular activities (e.g. carbon/nitrogen
      fixation/turnover), STXM provides information on the location and chemical
      speciation of metabolites and products of redox reactions. We propose the
      combined use of both techniques and discuss the technical challenges of their
      joint application. Both techniques have the potential to enhance our
      understanding of cellular mechanisms and activities that contribute to
      microbially mediated processes, such as the biogeochemical cycling of elements,
      the transformation of contaminants and the precipitation of mineral phases.

PMID- 22409444
TI  - Decontamination of clothing and building materials associated with the
      clandestine production of methamphetamine.
AB  - This study was designed to determine how easily methamphetamine can be removed
      from clothing and building materials, utilizing different cleaning materials and
      methods. The study also addressed the penetration of methamphetamine into drywall
      and the ability of paints to encapsulate the methamphetamine on drywall. Clothing
      and building materials were contaminated in a stainless steel chamber by
      aerosolizing methamphetamine in a beaker heater. The amount of methamphetamine
      surface contamination was determined by sampling a grid pattern on the material
      prior to attempting to clean the materials. After cleaning, the materials were
      again sampled, and the degree of decontamination noted. We found that household
      clothing and response gear worn by first responders was easily decontaminated
      using a household detergent in a household washing machine. A single wash removed
      over 95% of the methamphetamine from these materials. The study also indicated
      that methamphetamine-contaminated, smooth non-porous surfaces can be easily
      cleaned to below detectable levels using only mild cleaners. More porous surfaces
      such as plywood and drywall were unlikely to be decontaminated to below
      regulatory levels even with three washes using a mild cleaner. This may be due to
      methamphetamine penetration into the paint on these surfaces. Evaluation of
      methamphetamine contamination on drywall indicated that approximately 40% of the
      methamphetamine was removed using a wipe, while another 60% remained in the paint
      layer. Stronger cleaners such as those with active ingredients including sodium
      hypochlorite or quaternary ammonia and commercial decontamination agents were
      more effective than mild detergent-based cleaners and may reduce methamphetamine
      contamination to below regulatory levels. Results from the encapsulation studies
      indicate that sprayed on oil-based paint will encapsulate methamphetamine on
      drywall and plywood surfaces up to 4.5 months, while latex paints were less
      effective.

PMID- 22409445
TI  - Uniform, dense arrays of vertically aligned, large-diameter single-walled carbon
      nanotubes.
AB  - Precisely controlled reactive chemical vapor synthesis of highly uniform, dense
      arrays of vertically aligned single-walled carbon nanotubes (SWCNTs) using
      tailored trilayered Fe/Al(2)O(3)/SiO(2) catalyst is demonstrated. More than 90%
      population of thick nanotubes (>3 nm in diameter) can be produced by tailoring
      the thickness and microstructure of the secondary catalyst supporting SiO(2)
      layer, which is commonly overlooked. The proposed model based on the atomic force
      microanalysis suggests that this tailoring leads to uniform and dense arrays of
      relatively large Fe catalyst nanoparticles on which the thick SWCNTs nucleate,
      while small nanotubes and amorphous carbon are effectively etched away. Our
      results resolve a persistent issue of selective (while avoiding multiwalled
      nanotubes and other carbon nanostructures) synthesis of thick vertically aligned
      SWCNTs whose easily switchable thickness-dependent electronic properties enable
      advanced applications in nanoelectronic, energy, drug delivery, and membrane
      technologies.

PMID- 22409446
TI  - Quantification of protein incorporated into electrospun polycaprolactone tissue
      engineering scaffolds.
AB  - The surface modification of synthetic tissue engineering scaffolds is essential
      to improving their hydrophilicity and cellular compatibility. Plasma treatment is
      an effective way to increase the hydrophilicity of a surface, but the
      incorporation of biomolecules is also important to control cellular adhesion and
      differentiation, among many other outcomes. In this work, oriented
      polycaprolactone (PCL) electrospun fibers were modified by air-plasma treatment,
      followed by the covalent attachment of laminin. The amount of protein
      incorporated onto the fiber surface was controlled by varying the reaction time
      and the protein solution concentration. The protein concentration and coverage
      were quantified using X-ray photoelectron spectroscopy (XPS), solid-state
      ultraviolet-visible spectroscopy (UV-vis) and two fluorescence-based assays. XPS
      results showed a nearly linear increase in protein coverage with increasing
      protein soaking solution concentration until a monolayer was formed. Results from
      XPS and the NanoOrange fluorescence assay revealed multilayer protein coverage at
      protein solution concentrations between 25 and 50 MUg/mL, whereas the UV-vis
      assay demonstrated multilayer coverage at lower protein solution concentrations.
      The effect of protein concentration on the neurite outgrowth of neuron-like PC12
      cells was evaluated, and outgrowth rates were found to be positively correlated
      to increasing protein concentration.

PMID- 22409447
TI  - Association of single nucleotide polymorphic sites in candidate genes with
      aggressiveness and deoxynivalenol production in Fusarium graminearum causing
      wheat head blight.
AB  - BACKGROUND: Fusarium graminearum sensu stricto (s.s.) is an ubiquitous pathogen
      of cereals. The economic impact of Fusarium head blight (FHB) is characterized by
      crop losses and mycotoxin contamination. Our objective was to associate SNP
      diversity within candidate genes with phenotypic traits. A total of 77 F.
      graminearum s.s. isolates was tested for severity of fungal infection (=
      aggressiveness) and deoxynivalenol (DON) production in an inoculated field
      experiment at two locations in each of two years. For seven genes known to
      control fungal growth (MetAP1, Erf2) or DON production (TRI1, TRI5, TRI6 TRI10
      and TRI14) single nucleotides polymorphic sites (SNPs) were determined and
      evaluated for the extent of linkage disequilibrium (LD). Associations of SNPs
      with both phenotypic traits were tested using linear mixed models. RESULTS: Decay
      of LD was in most instances fast. Two neighboring SNPs in MetAP1 and one SNP in
      Erf2 were significantly (P < 0.05) associated with aggressiveness explaining
      proportions of genotypic variance (pG) of 25.6%, 0.5%, and 13.1%, respectively.
      One SNP in TRI1 was significantly associated with DON production (pG = 4.4).
      CONCLUSIONS: We argue that using the published sequence information of Fusarium
      graminearum as a template to amplify comparative sequence parts of candidate
      genes is an effective method to detect quantitative trait loci. Our findings
      underline the potential of candidate gene association mapping approaches to
      identify functional SNPs underlying aggressiveness and DON production for F.
      graminearum s.s populations.

PMID- 22409448
TI  - Valproic acid attenuates blood-spinal cord barrier disruption by inhibiting
      matrix metalloprotease-9 activity and improves functional recovery after spinal
      cord injury.
AB  - The disruption of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI)
      elicits an intensive local inflammation by the infiltration of blood cells such
      as neutrophils and macrophages, leading to cell death and permanent neurological
      disability. SCI activates matrix metalloprotease-9 (MMP-9), which is known to
      induce BSCB disruption. Here, we examined whether valproic acid (VPA), a histone
      deacetylase inhibitor, would attenuate BSCB disruption by inhibiting MMP-9
      activity, leading to improvement of functional outcome after SCI. After moderate
      spinal cord contusion injury at T9, VPA (300 mg/kg) were immediately injected
      subcutaneously and further injected every 12 h for 5 days. Our data show that VPA
      inhibited MMP-9 activity after injury, and attenuated BSCB permeability and
      degradation of tight junction molecules such as occludin and ZO-1. In addition,
      VPA reduced the expression of inflammatory mediators including tumor necrosis
      factor-alpha. Furthermore, VPA increased the levels of acetylated histone 3,
      pAkt, and heat-shock protein 27 and 70, which have anti-apoptotic functions after
      SCI. Finally, VPA inhibited apoptotic cell death and caspase 3 activation,
      reduced the lesion volume and improved functional recovery after injury. Thus,
      our results demonstrated that VPA improves functional recovery by attenuating
      BSCB disruption via inhibition of MMP-9 activity after SCI.

PMID- 22409449
TI  - Evaluating the properties of the Evidence-Based Practice Attitude Scale (EBPAS)
      in health care.
AB  - The Evidence-Based Practice Attitude Scale (EBPAS; Aarons, 2004) is a relatively
      new construct for the study of attitudes toward the adoption of innovation and
      evidence-based practices (EBPs) in mental health service settings. Despite
      widespread interest in measuring the attitudes of health care providers in
      conjunction with the adoption of EBPs, no prior research has used the EBPAS with
      medical doctors, a different population than that with which the scale was
      originally developed. In the present study, the factor structure, reliability,
      and validity of EBPAS scores were tested with a sample of 534 medical doctors
      working in 14 Greek hospitals. In addition, associations of health care provider
      characteristics (age, gender, medical specialty, information and communication
      technology use and knowledge) with EBPAS total scores are examined. Confirmatory
      factor analyses support the 4-factor structure of the EBPAS and provide
      convincing evidence for the validity of the scale. Implications and future
      directions are discussed.

PMID- 22409451
TI  - Local heat application enhances glycogenesis.
AB  - The purpose of this study was to determine the impact of increased local muscle
      temperature independent of core temperature on glycogenesis during recovery from
      exercise when adequate carbohydrate provisions were supplied. Nine recreationally
      active males (age, 23 +/- 4 years; height, 178 +/- 6 cm; weight 79 +/- 9 kg)
      cycled for 92 min and recovered for 4 h. During recovery the subject's legs were
      randomly assigned as the heated limb (heat pack application) and control limb
      (exposed to room air). Participants received 2 carbohydrate feedings (1.8 g.kg(
      1) of body weight) at 0 and 2 h of recovery. Core temperature, intramuscular
      temperature, and leg circumference were monitored throughout recovery. Skeletal
      muscle biopsies samples of the vastus lateralis were obtained at the beginning
      and end of the 4-h recovery period on both legs and analyzed for glycogen and
      lactate. Core temperature did not change from throughout recovery. Muscle
      temperature in the heated limb was higher by 15 min and remained elevated
      throughout recovery compared with the control limb (p < 0.05). Leg circumference
      was not different between limbs. Lactate increased from postexercise to 4 h
      postexercise regardless of trial (p < 0.05). Muscle glycogen concentration
      increased with recovery and carbohydrate feeding in both limbs (p < 0.05) but was
      22% higher in the heated limb compared with the control limb (p < 0.05). This
      study demonstrates increased glycogenesis when local muscle temperature is
      increased independent of core temperature.

PMID- 22409452
TI  - 17beta-estradiol attenuates neural cell apoptosis through inhibition of JNK
      phosphorylation in SCI rats and excitotoxicity induced by glutamate in vitro.
AB  - We investigated whether 17beta-estradiol (E2) treatment could prevent the
      apoptosis of neural cells after spinal cord injury (SCI) and cultured cortical
      cells through inhibition of JNK (c-Jun N-terminal kinase) phosphorylation. SCI
      induced rats were randomly divided into three groups: control, E2-treated, and
      sham-treated. Five rats from each group were sacrificed at 2, 4, 6, 12, or 24 h
      postinjury. Apoptotic neural cells were assessed using the TUNEL method. JNK
      phosphorylation was detected with immunohistochemistry. Cultured cortical cells
      were pretreated with E2 and the specific JNK inhibitor SP600125 and then treated
      with glutamate-induced cytotoxicity in vitro. Neuron viability was determined
      with an methyl thiazolyl tetrazolium (MTT) assay, morphology of apoptotic cells
      was observed with 4',6-diamidino-2-phenylindole (DAPI) staining, and JNK
      phosphorylation was detected using Western blot analysis. Treatment with E2
      reduced neuron apoptosis and inhibited JNK phosphorylation. Moreover, the number
      of apoptotic cells was correlated with JNK phosphorylation 24 h after the rats
      suffered the SCI. Pretreatment with E2 significantly maintained neural cell
      viability, attenuated apoptosis, and inhibited JNK phosphorylation induced by
      glutamate in vitro. These neuroprotective effects of E2 on neural cells were
      blocked by the co-administration of SP600125. Our results suggest that
      neuroprotection from E2 is partially mediated by the inhibition of JNK
      phosphorylation.

PMID- 22409453
TI  - Minoxidil use in dermatology, side effects and recent patents.
AB  - Minoxidil, a vasodilator medication known for its ability to slow or stop hair
      loss and promote hair regrowth, was first introduced, exclusively as an oral
      drug, to treat high blood pressure. It was however discovered to have the
      important side-effect of increasing growth or darkening of fine body hairs; this
      led to the development of a topical formulation as a 2% concentration solution
      for the treatment of female androgenic alopecia or 5% for treating male
      androgenic alopecia. Measurable changes disappear within months after
      discontinuation of treatment. The mechanism by which it promotes hair growth is
      not fully understood. Minoxidil is a potassium channel opener, causing
      hyperpolarization of cell membranes and it is also a vasodilator, it is
      speculated that, by widening blood vessels and opening potassium channels, it
      allows more oxygen, blood and nutrients to the follicle. This can also cause
      follicles in the telogen phase to shed, usually soon to be replaced by new,
      thicker hairs in a new anagen phase. It needs to be applied regularly, once or
      twice daily, for hair gained to be maintained, and side effects are common. The
      most common adverse reactions of the topical formulation are limited to irritant
      and allergic contact dermatitis on the scalp. There have been cases of allergic
      reactions to the nonactive ingredient propylene glycol, which is found in some
      topical solution especially if they are galenic. Increased hair loss which can
      occur during Minoxidil use, is due to the synchronization of the hair cycle that
      the treatment induces. In this review, we described its mechanism of action, use
      in dermatology and some patents related to alternative treatment of allergic
      reactions due to its use.

PMID- 22409454
TI  - Outcome and complications of long-term self-expanding esophageal stenting.
AB  - Esophageal stenting with self-expanding plastic or covered metal stents is
      believed to be safe and effective. As data on the outcome of patients with long
      term stenting are not available, this study was conducted to evaluate the safety
      and efficacy of long-term esophageal stenting. From 2002 to 2008, 70 patients
      with long-term esophageal stenting for various indications from a prospective
      database were included into further analysis. The median stent period was 297
      (124-1980) days during a mean follow-up time of 55 +/- 52.4 months. Overall
      complication rate was 30% with a primary success rate of 97.2%. The stent-related
      total reintervention rate was 17.1%. There were no correlations between stent
      characteristics and the risk of complication or migration. No stent-related death
      was observed. Our data provide evidence that long-period esophageal stenting is
      safe and effective for various indications.

PMID- 22409455
TI  - Apoptosis and microRNA aberrations in cancer.
AB  - Carcinogenesis arises from the malfunction of genes that control cell growth and
      division. Therefore, the most effective method of hindering tumourigenesis is to
      induce the death of immortalized cancer cells. Apoptosis or programmed cell death
      has shown the most promises in impairing cancer growth. A variety of proteins is
      involved in the regulation of apoptosis and the malfunction of any these
      regulators may cause cell proliferation. The microRNAs have been shown to play a
      central role in the regulation of the cell cycle, including apoptosis. The
      microRNAs are involved in post-transcriptional gene suppression and have been
      implicated in the regulation of cell differentiation and development. Aberrations
      in the microRNA regulation of apoptosis lead to tumourigenesis. The present
      review assesses the current knowledge of apoptotic regulation in cancer and the
      effect of microRNA aberrations in tumourigenesis.

PMID- 22409456
TI  - BINAPHANE-catalyzed asymmetric synthesis of trans-beta-lactams from disubstituted
      ketenes and N-tosyl arylimines.
AB  - The development of a BINAPHANE-catalyzed formal [2 + 2]-cycloaddition of
      disubstituted ketenes and inexpensive N-tosyl arylimines that provides access to
      a variety of highly substituted beta-lactams (16 examples) is described. The
      BINAPHANE catalytic system displays moderate to excellent enantioselectivity (up
      to 98% ee) and high diastereoselectivity in most cases, favoring formation of the
      trans-diastereomer (13 examples with dr >= 90:10).

PMID- 22409457
TI  - Fighting fire with fire: rewiring tumor cells for oncolytic virotherapy.

PMID- 22409458
TI  - FoxM1: a potential drug target for glioma.

PMID- 22409460
TI  - Evaluation of MVA-5T4 as a novel immunotherapeutic vaccine in colorectal, renal
      and prostate cancer.
AB  - This paper reviews the development of the combination of modified vaccinia Ankara
      (MVA) to deliver the tumor-associated antigen 5T4 as a novel immunotherapeutic
      vaccine. The oncofetal antigen 5T4 is highly expressed in 80% of breast, kidney,
      colorectal, prostate and ovarian carcinomas, making it an ideal antigen for
      vaccine therapy. To date, more than 3000 doses of MVA-5T4 have been administered
      to colorectal, renal and prostate cancer patients, with rare occurrences of grade
      3 or 4 vaccination-related adverse events being observed. Studies have
      demonstrated that MVA-5T4 is safe and highly immunogenic, both as monotherapy and
      in combination with other standard of care therapies. Although an immune response
      has been observed, antitumor activity has been modest or absent in clinical
      trials. A Phase III trial resulted in the development of an immune response
      surrogate that is to be applied to all future MVA-5T4 clinical trials. With
      minimal side effects and the ability to produce a strong immunogenic response,
      MVA-5T4 is a viable addition to the cancer therapy arsenal.

PMID- 22409461
TI  - Surgical considerations in patients receiving neoadjuvant systemic therapy.
AB  - Neoadjuvant chemotherapy is being increasingly used in the treatment of patients
      presenting with early-stage, operable breast cancer. Neoadjuvant chemotherapy
      downsizes most tumors, allowing appropriately selected patients to undergo breast
      conserving therapy. Management of the axilla in patients receiving neoadjuvant
      chemotherapy is dictated by whether patients present with clinically node
      negative or node-positive disease. Patients with clinically node-negative disease
      can undergo sentinel lymph node dissection after neoadjuvant chemotherapy, with
      axillary lymph node dissection reserved for patients with a positive sentinel
      lymph node. For patients with clinically node-positive disease at presentation,
      the current standard of care is axillary lymph node dissection. An ongoing
      cooperative group trial is investigating the utility of sentinel lymph node
      surgery in the clinically node-positive population.

PMID- 22409462
TI  - Cortical dysplasia: a possible substrate for brain tumors.
AB  - The similarities between brain tumor stem cells and neural stem cells suggest a
      possible stem cell origin of tumorigenesis. Recently, cells with features of stem
      cells have been observed in lesions of adult and pediatric cortical dysplasia
      (CD). Given the evidence for a close relationship between CD and certain brain
      tumors, together with the finding that CD neural stem cells/progenitors are
      abnormally developed, we propose that CD is a possible substrate for brain
      tumors. The neural stem cells/progenitors in CD have accumulating abnormalities,
      and these abnormal stem/progenitor cells may be the initiating, transformed cells
      of brain tumors, when subsequently exposed to a carcinogen.

PMID- 22409464
TI  - Endocrine resistance in breast cancer: molecular pathways and rational
      development of targeted therapies.
AB  - Endocrine resistance presents a major challenge in the management of estrogen
      receptor (ER)-positive breast cancer and is an area under intense investigation.
      Although the underlying mechanism is still poorly understood, many studies point
      towards the 'cross-talk' between ER and growth factor receptor signaling pathways
      as the key in the development of estrogen-independent growth in breast cancer.
      This review aims to provide the reader our current understanding of various
      molecular pathways that mediate endocrine resistance and that are being evaluated
      as therapeutic targets for ER-positive breast cancer. While most of the agents
      that target these pathways have only been tested in Phase I or small Phase II
      trials, some have shown encouraging results. A critical issue that remains is the
      development of research strategies and clinical trials that take into account the
      molecular heterogeneity of ER-positive breast cancer.

PMID- 22409463
TI  - High-throughput screening strategies for targeted identification of therapeutic
      compounds in colorectal cancer.
AB  - Recent advancements in understanding the role of both genetics and molecular
      pathways in the formation and progression of colorectal cancer have allowed the
      identification of factors that may be targeted for drug discovery. During the
      past decade, various approaches have been developed to target specific steps or
      components of these pathways in order to prevent the development and progression
      of colorectal cancer and to treat this disease. The innovation and optimization
      of high-throughput screening methods, as well as the recent emphasis from the NIH
      on translational sciences, have enabled rapid progress in drug discovery in many
      fields, including colorectal cancer. Here we present a summary of the recent
      efforts of targeted high-throughput drug discovery directed at pathways affected
      in colorectal cancer.

PMID- 22409465
TI  - Systemic treatment of malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma is a rare malignancy with a dismal prognosis. The
      clinical management of most of the patients with this disease is quite
      challenging, and, overall, the therapeutic strategy has not yet benefited from
      the recent advances in molecular biology. Randomized evidence supports the use of
      cisplatin in combination with pemetrexed or raltitrexed as first-line treatments.
      In elderly patients with comorbidities cisplatin may be replaced by carboplatin
      because of a lesser burden of toxicities. The role of second-line chemotherapy is
      unproven, although pemetrexed can be regarded as the standard option in
      pemetrexed-naive patients and therapeutic rechallenge with pemetrexed may be
      considered in selected patients with prolonged disease control after first-line
      therapy. Targeted therapies failed to demonstrate any substantial activity;
      however, immunotherapies may complement other treatment strategies. In summary,
      there is an unmet clinical need and innovative approaches to select new
      potentially active drugs are highly warranted.

PMID- 22409466
TI  - Optical spectroscopy: current advances and future applications in cancer
      diagnostics and therapy.
AB  - Optical spectroscopy (OS) is a tissue-sensing technique that could enhance cancer
      diagnosis and treatment in the near future. With OS, tissue is illuminated with a
      selected light spectrum. Different tissue types can be distinguished from each
      other based on specific changes in the reflected light spectrum that are a result
      of differences on a molecular level between compared tissues. Therefore, OS has
      the potential to become an important optical tool for cancer diagnosis and
      treatment monitoring. In recent years, significant progress has been made in the
      discriminating abilities of OS techniques between normal and cancer tissues of
      multiple human tissue types. This article provides an overview of the advances
      made with diffuse reflectance, fluorescence and Raman spectroscopy techniques in
      the field of clinical oncology, and focuses on the different clinical
      applications that OS could enhance.

PMID- 22409467
TI  - The current role of circulating tumor cells in the diagnosis and management of
      bone metastases in advanced prostate cancer.
AB  - Prostate-specific antigen (PSA) has been used for over two decades as a serum
      marker for adenocarcinoma of the prostate. Although PSA screening remains an
      important part of disease screening and monitoring in early prostate cancer (PC),
      its utility in monitoring disease progression in advanced PC is undetermined.
      Furthermore, the role of PSA monitoring in the management of patients with PC and
      bone metastases appears limited. The purpose of this review is to evaluate the
      role of circulating tumor cells (CTCs) as potential novel biomarkers in advanced
      PC. We present a review of CTC testing and the clinical data supporting the
      prognostic potential of CTCs in this setting. We propose that combination of CTCs
      and PSA velocity or doubling-time assessments may offer insights into the
      prognosis and management of advanced PC.

PMID- 22409468
TI  - Anal metastasis from breast cancer: a case report and review of the literature.
AB  - Breast cancer usually metastasizes towards the lymph nodes, lung, bone, liver or
      brain; metastatic gastrointestinal involvement is rare and anal metastases are
      extremely rare. Necroscopic studies report a 6-18% incidence of extra-hepatic
      gastrointestinal metastases, and the most frequent sites of the GI tract involved
      are the stomach and the small intestine. We report a case with anal metastasis
      from breast cancer and a review of the associated literature.

PMID- 22409470
TI  - Acrodynia and hypertension in a young girl secondary to elemental mercury
      toxicity acquired in the home.
AB  - Acrodynia, also known as pink disease, erythredema polyneuropathy, Feer syndrome,
      and raw-beef hands and feet, is thought to be a toxic reaction to elemental
      mercury and less commonly to organic and inorganic forms. Occurring commonly in
      the early 20th century, acrodynia is now a seemingly extinct disease in the
      modern world because of regulations to eliminate mercury from personal care
      products, household items, medications, and vaccinations. We present a case of a
      3-year-old girl with acrodynia secondary to toxic exposure to elemental mercury
      in the home environment.

PMID- 22409471
TI  - Generalized pustular psoriasis in a child: observation of long-term combination
      therapy with etretinate and calcipotriol for 16 years.
AB  - Generalized pustular psoriasis (GPP) is a rare condition in young children. It is
      difficult to treat and may require long-term systemic therapy. We report the long
      term course of a 3-year-old boy whose onset of psoriasis dated to age 7 months.
      He was treated with etretinate and psoralen plus ultraviolet A therapy initially
      and then with etretinate alone, and at age 12, topical calcipotriol was added. At
      the age of 19, he had been taking oral retinoids for 16 years, with a mean dose
      of etretinate of 0.22 mg/kg per day, a total amount of approximately 37 g,
      without evidence of stunted growth, ligamentous calcification, hyperostosis, or
      hepatic toxicity.

PMID- 22409472
TI  - A giant congenital plaque.

PMID- 22409473
TI  - Painful vulvar nodule.

PMID- 22409474
TI  - Fourteen-month-old girl with facial skin thinning.

PMID- 22409475
TI  - Wells' syndrome presenting as a noninfectious bullous cellulitis in a child.
AB  - Wells' syndrome is a rare disease that is even more uncommon in childhood. This
      case report illustrates the potential devastating extent of the disease and
      highlights the unusual presentation of bullae in a child. It is imperative to
      consider Wells' syndrome in patients with presumed cellulitis and eosinophilia
      who fail to respond to antibiotics.

PMID- 22409476
TI  - Long-term follow-up of previously reported case of trichomegaly associated with
      alopecia areata in a 3-year-old girl.

PMID- 22409477
TI  - Induction of cytokines in a macrophage cell line by proteins of Clostridium
      difficile.
AB  - Clostridium difficile is a major cause of nosocomial diarrhoea. The toxins
      produced by C. difficile are responsible for the characteristic pathology
      observed in C. difficile disease, but several surface-associated proteins of C.
      difficile are also recognized by the immune system and could modulate the immune
      response in infection. The aim of this study was to assess the induction of
      cytokines in a macrophage cell line in response to different antigens prepared
      from five C. difficile strains: the hypervirulent ribotype 027, ribotypes 001 and
      106 and reference strains VPI 10463 and 630 (ribotype 012). PMA-activated THP-1
      cells were challenged with surface-layer proteins, flagella, heat-shock proteins
      induced at 42 and 60  degrees C and culture supernatants of the five C. difficile
      strains. The production of the pro-inflammatory cytokines such as TNF-alpha, IL
      1beta, IL-6, IL-8 and IL-12p70 was observed in response to the surface-associated
      proteins, and high levels of TNF-alpha, IL-1beta and IL-8 were detected in
      response to challenge with culture supernatants. The immune response triggered by
      the surface-associated proteins was independent of the strain from which the
      antigens were derived, suggesting that these proteins might not be related to the
      varying virulence of the hypervirulent ribotype 027 or ribotypes 001 and 106.
      There was no interstrain difference observed in response to the culture
      supernatants of the tested C. difficile strains, but this was perhaps due to
      toxicity induced in the macrophages by large amounts of toxin A and toxin B.

PMID- 22409478
TI  - Light energy conversion by mesoscopic PbS quantum dots/TiO2 heterojunction solar
      cells.
AB  - Solid state PbS quantum dots (QDs)/TiO(2) heterojunction solar cells were
      produced by depositing PbS QDs on a 500 nm thick mesoscopic TiO(2) films using
      layer-by-layer deposition. Importantly, the PbS QDs act here as photosensitizers
      and at the same time as hole conductors. The PbS QDs/TiO(2) device produces a
      short circuit photocurrent (J(sc)) of 13.04 mA/cm(2), an open circuit
      photovoltage (V(oc)) of 0.55 V and a fill factor (FF) of 0.49, corresponding to a
      light to electric power conversion efficiency (eta) of 3.5% under AM1.5
      illumination. The electronic processes occurring in this device were investigated
      by transient photocurrent and photovoltage measurements as well as impedance
      spectroscopy in the dark and under illumination. The investigations showed a high
      resistivity for the QD/metal back contact, which reduces drastically under
      illumination. EIS also indicated a shift of the depletion layer capacitance under
      illumination related to the change of the dipole at this interface.

PMID- 22409479
TI  - Giving anemia a boost with inhibitors of prolyl hydroxylase.
AB  - There is much current interest in the development of inhibitors of the prolyl
      hydroxylase (PHD) enzymes that regulate the hypoxia-inducible transcription
      factor (HIF), which in turn stimulates the production of erythropoietin and
      ultimately red blood cells, as a treatment for anemia. A recent paper reports the
      synthesis and evaluation of a novel class of potent spirohydantoin-based pan-PHD
      inhibitors for this purpose. The paper is an exemplar of drug development from
      high-throughput screen to clinical candidate.

PMID- 22409480
TI  - Reactivity of a tin(II) (iminophosphinoyl)(thiophosphinoyl)methanediide complex
      toward sulfur: synthesis and 119Sn Mossbauer spectroscopic studies of [{(MU
      S)SnC(PPh2?NSiMe3)(PPh2?S)}3Sn(MU3-S)].
AB  - Reaction of [(PPh(2)?NSiMe(3))(PPh(2)?S)CSn:](2) (1) with elemental sulfur in
      toluene afforded [{(MU-S)Sn(IV)C(PPh(2)?NSiMe(3))(PPh(2)?S)}(3)Sn(II)(MU(3)-S)]
      (2) and [CH(2)(PPh(2)?NSiMe(3))(PPh(2)?S)] (3). Compound 2 comprises a Sn(II)S
      moiety coordinated with the Sn(IV) and S atoms of a trimeric 2
      stannathiomethendiide {(PPh(2)?NSiMe(3))(PPh(2)?S)CSn(MU-S)}(3). Compound 2 has
      been characterized by NMR spectroscopy, (119)Sn Mossbauer studies, X-ray
      crystallography, and theoretical studies. (119)Sn NMR spectroscopy and Mossbauer
      studies show the presence of Sn(IV) and Sn(II) atoms in 2. X-ray crystallography
      suggests that the Sn(II)S moiety does not have multiple bond character.
      Theoretical studies illustrate that the C(methanediide)-Sn bonds comprise a lone
      pair orbital on each C(methanediide) atom and an C-Sn occupied sigma orbital.

PMID- 22409481
TI  - Was the military operation "Cast Lead" a risk factor for preterm deliveries?
AB  - OBJECTIVE: To investigate the influence of operation "Cast Lead" on rates of
      preterm delivery (PTD) and other adverse pregnancy outcomes at the main region
      under missile attack during the operation. METHODS: A retrospective cohort study
      comparing pregnancy and delivery outcomes of women who gave birth at the time of
      the military operation "Cast Lead" with women who gave birth at the same time
      period 1 and 2 years before and after the war. RESULTS: Out of 1272 women exposed
      to stress during the war, there were 126 preterm deliveries (9.9%) as compared
      with 381 preterm deliveries (9.6%) among the 3984 women of the control group (p =
      0.719). The group exposed to stress of the military campaign had significantly
      more preterm deliveries at gestational age 32-34 weeks (1.6% vs. 0.8%; RR = 2.04,
      p = 0.011). CONCLUSION: Military operation period was adversely associated with
      an increase in the rate of early PTD (<34 weeks gestation). From a public health
      perspective, pregnant women should be considered a special population and should
      be taken into account in a preparedness program for an emergency crisis and must
      be an important part of the public agenda and the state's infrastructure.

PMID- 22409482
TI  - Reduced palatability in drug-induced taste aversion: II. Aversive and rewarding
      unconditioned stimuli.
AB  - Drugs of abuse are known to reduce intake of a taste conditioned stimulus
      (conditional stimulus, CS), a behavioral response sometimes seen as paradoxical
      because the same drugs also serve as rewards in other behavioral procedures. In
      the present study we compared patterns of intake and palatability (assessed using
      microstructural analysis of licking) for a standard saccharin CS paired with the
      following: lithium chloride, morphine, amphetamine, or sucrose. We found that
      morphine and amphetamine, like lithium-induced illness, each suppressed CS intake
      and caused a reduction in saccharin palatability. Sucrose, a rewarding stimulus,
      did not reduce the palatability of the saccharin CS. We interpret these finds as
      evidence that drugs of abuse induce conditioned taste aversions.

PMID- 22409483
TI  - The reliability of hospital and pharmaceutical data to assess prevalent cases of
      chronic obstructive pulmonary disease.
AB  - Identifying chronic obstructive disease (COPD) cases is required to estimate COPD
      prevalence, to enroll COPD cohorts and to estimate air pollution health effects.
      Administrative health data are frequently used to identify COPD cases, though
      their validity has not been satisfactorily assessed. This paper aims to assess
      the contribution of pharmaceutical data in detecting COPD cases and to estimate
      the reliability of hospital/mortality databases in detecting COPD cases.
      Prevalent COPD cases among 35-plus-year-olds were estimated in four Italian areas
      in 2006 from hospital/mortality registries and adding pharmaceutical data. Age
      specific and age-standardized prevalence rates were calculated in each area.
      Internal validity of COPD diagnoses from hospital and mortality databases was
      assessed. Pharmaceutical database was used to confirm the hospital/mortality COPD
      cases and to examine the selection and misclassification of hospitalized cases.
      Possible misclassification between COPD and asthma cases was estimated using
      hospital data. Prevalent COPD cases were 77,098 from hospital/mortality
      registries, 172,357 when respiratory prescriptions were added. Prevalence ranged
      from 4.0%-6.7%. Only 22.7% of pharmaceutical COPD cases were hospitalized or died
      and only 37.2% of hospital/mortality cases consumed respiratory medicines; this
      last proportion increased to 64.5% among the older cases with a principal
      diagnosis. COPD cases with a contemporary asthma diagnosis were 3.1%. We found
      that pharmaceutical data increases COPD prevalence estimates 2.2-2.5 times.
      Hospitalization does not necessarily indicate COPD severity, COPD as a principal
      diagnosis confirmed with medicine prescription more likely represented true
      cases. Misclassification affects asthma cases to greater extent than COPD cases.

PMID- 22409484
TI  - The tomato SlIAA15 is involved in trichome formation and axillary shoot
      development.
AB  - The Aux/IAA genes encode a large family of short-lived proteins known to regulate
      auxin signalling in plants. Functional characterization of SlIAA15, a member of
      the tomato (Solanum lycopersicum) Aux/IAA family, shows that the encoded protein
      acts as a strong repressor of auxin-dependent transcription. The physiological
      significance of SlIAA15 was addressed by a reverse genetics approach, revealing
      that SlIAA15 plays multiple roles in plant developmental processes. The SlIAA15
      down-regulated lines display lower trichome number, reduced apical dominance with
      associated modified pattern of axillary shoot development, increased lateral root
      formation and decreased fruit set. Moreover, the leaves of SlIAA15-inhibited
      plants are dark green and thick, with larger pavement cells, longer palisade
      cells and larger intercellular space of spongy mesophyll cells. The SlIAA15
      suppressed plants exhibit a strong reduction in type I, V and VI trichome
      formation, suggesting that auxin-dependent transcriptional regulation is required
      for trichome initiation. Concomitant with reduced trichome formation, the
      expression of some R2R3 MYB genes, putatively involved in the control of trichome
      differentiation, is altered. These phenotypes uncover novel and specialized roles
      for Aux/IAAs in plant developmental processes, clearly indicating that members of
      the Aux/IAA gene family in tomato perform both overlapping and specific
      functions.

PMID- 22409485
TI  - Understanding savant skills in autism.

PMID- 22409486
TI  - In vitro assessment of alkylglyceryl-functionalized chitosan nanoparticles as
      permeating vectors for the blood-brain barrier.
AB  - A series of O-substituted alkylglyceryl chitosans with systematically varied
      alkyl chain length and degree of grafting has been employed for the formulation
      of aqueous nanoparticulate systems, which were in turn investigated for their
      effects on a modeled blood-brain-barrier system of mouse-brain endothelial cells.
      Barrier function measurements employing electric cell-substrate impedance sensing
      and analyses of tight junction-specific protein profiles have indicated that the
      alkylglyceryl-modified chitosan nanoparticles impact upon the integrity of the
      model blood-brain barrier, whereas confocal microscopy experiments have
      demonstrated the efficient cellular uptake and the perinuclear localization of
      these nanoparticles. The application of nanoparticles to the model blood-brain
      barrier effected an increase in its permeability, as demonstrated by following
      the transport of the tracer molecule fluorescein isothiocyanate.

PMID- 22409487
TI  - The role of prevention focus under stereotype threat: Initial cognitive
      mobilization is followed by depletion.
AB  - Previous research has demonstrated that stereotype threat induces a prevention
      focus and impairs central executive functions. The present research examines how
      these 2 consequences of stereotype threat are related. The authors argue that the
      prevention focus is responsible for the effects of stereotype threat on executive
      functions and cognitive performance. However, because the prevention focus is
      adapted to deal with threatening situations, the authors propose that it also
      leads to some beneficial responses to stereotype threat. Specifically, because
      stereotype threat signals a high risk of failure, a prevention focus initiates
      immediate recruitment of cognitive control resources. The authors further argue
      that this response initially facilitates cognitive performance but that the
      additional cognitive demands associated with working under threat lead to
      cognitive depletion over time. Study 1 demonstrates that stereotype threat (vs.
      control) facilitates immediate cognitive control capacity during a stereotype
      relevant task. Study 2 experimentally demonstrates the process by showing that
      stereotype threat (vs. control) facilitates cognitive control as a default, as
      well as when a prevention focus has been experimentally induced, but not when a
      promotion focus has been induced. Study 3 shows that stereotype threat
      facilitates initial math performance under a prevention focus, whereas no effect
      is found under a promotion focus. Consistent with previous research, however,
      stereotype threat impaired math performance over time under a prevention focus,
      but not under a promotion focus.

PMID- 22409488
TI  - Genomic variation in Salmonella enterica core genes for epidemiological typing.
AB  - BACKGROUND: Technological advances in high throughput genome sequencing are
      making whole genome sequencing (WGS) available as a routine tool for bacterial
      typing. Standardized procedures for identification of relevant genes and of
      variation are needed to enable comparison between studies and over time. The core
      genes--the genes that are conserved in all (or most) members of a genus or
      species--are potentially good candidates for investigating genomic variation in
      phylogeny and epidemiology. RESULTS: We identify a set of 2,882 core genes
      clusters based on 73 publicly available Salmonella enterica genomes and evaluate
      their value as typing targets, comparing whole genome typing and traditional
      methods such as 16S and MLST. A consensus tree based on variation of core genes
      gives much better resolution than 16S and MLST; the pan-genome family tree is
      similar to the consensus tree, but with higher confidence. The core genes can be
      divided into two categories: a few highly variable genes and a larger set of
      conserved core genes, with low variance. For the most variable core genes, the
      variance in amino acid sequences is higher than for the corresponding nucleotide
      sequences, suggesting that there is a positive selection towards mutations
      leading to amino acid changes. CONCLUSIONS: Genomic variation within the core
      genome is useful for investigating molecular evolution and providing candidate
      genes for bacterial genome typing. Identification of genes with different degrees
      of variation is important especially in trend analysis.

PMID- 22409489
TI  - Influence of season and location on pulmonary response to California's San
      Joaquin Valley airborne particulate matter.
AB  - Season and location have documented impacts on particulate matter (PM)-induced
      morbidity and mortality. Seasonal and regional influences on the physical and
      chemical properties of PM2.5 (also known as fine/ultrafine PM) contribute to
      differences in exposure burden and adverse respiratory health outcomes
      experienced in California's San Joaquin Valley (SJV), which ranks among the worst
      in the nation for PM pollution. Current regulations are driven by the association
      between mass concentrations and adverse health outcomes. However, this
      association is difficult to reproduce in toxicological studies and suggests a
      role for other parameters, such as chemical composition, involved in PM-induced
      adverse pulmonary health effects. Pulmonary toxicity of summer/winter and
      rural/urban SJV PM was evaluated given the unique geography, metereology and
      sources of the region. Healthy juvenile male mice inhaled summer/winter and
      urban/rural concentrated ambient PM (CAP) or ambient PM for 6 h/d for 10 d, and
      pulmonary inflammatory responses were measured 48 h postexposure. Exposure
      concentrations ranged from 10 to 20 MUg/m3 for ambient air control mice and from
      86 to 284 MUg/m3. Mice exposed to rural but not urban CAP, displayed significant
      neutrophil influx that was more than 50-fold greater than control levels, which
      ranged from 21 to 60 neutrophils/ml for all experiments. Pulmonary neutrophilic
      inflammation was measured despite lower CAP concentrations in the rural compared
      to the urban location and in the absence of cytotoxicity, oxidative stress, or
      elevations in cytokine and chemokines expression. Further, the inflammatory
      responses induced by rural winter CAP were associated with the highest levels of
      organic carbon (OC) and nitrates (NO3-). Evidence indicates that
      regional/seasonal influences on PM chemical composition rather than PM mass may
      be associated with increased PM-induced adverse health effects.

PMID- 22409490
TI  - Lead (Pb) in biota and perceptions of Pb exposure at a recently designated
      Superfund beach site in New Jersey.
AB  - The Raritan Bay Slag Site (New Jersey) was designated a Superfund site in 2009
      because the seawall, jetties, and sediment contained lead (Pb). Our objective was
      to compare Pb and mercury (Hg) levels in biota and public perceptions of exposure
      at the Superfund and reference sites. Samples (algae, invertebrates, fish) were
      collected from the Raritan Bay Slag Site and reference sites and analyzed for Pb
      and Hg. Waterfront users were interviewed using a standard questionnaire. Levels
      of Pb in aquatic organisms were compared to ecological and human health safety
      standards. Lead levels were related to location, trophic level, and mobility.
      Lead levels in biota were highest at the western side of the West Jetty. Mean Pb
      levels were highest for algae (Fucus = 53,600 +/- 6990 ng/g = ppb [wet weight],
      Ulva = 23,900 +/- 2430 ppb), intermediate for grass shrimp (7270 +/- 1300 ppb,
      11,600 +/- 3340 ppb), and lowest for fish (Atlantic silversides 218 +/- 44 ppb).
      Within species, Pb levels varied significantly across the sampling sites. Lead
      levels in algae, sometimes ingested by individuals, were sufficiently high to
      exceed human safety levels. Mercury levels did not differ between the Superfund
      and reference sites. Despite the fence and warnings, people (1) used the
      Superfund and reference sites similarly, (2) had similar fish consumption rates,
      and (3) were not concerned about Pb, although most individuals knew the metal was
      present. The fish sampled posed no apparent risk for human consumers, but the
      algae did.

PMID- 22409491
TI  - Determination of tissue to blood partition coefficients for nonvolatile
      herbicides, insecticides, and fungicides using negligible depletion solid-phase
      microextraction (nd-SPME) and ultrafiltration.
AB  - Partition coefficients (PCs) are used in physiologically based pharmacokinetic
      (PBPK) models to estimate the free concentration of a chemical in specific blood
      or organs. Biological PC(tissue:blood) (tissue to blood) values were determined
      for a series of nonvolatile herbicides, insecticides, and fungicides in liver,
      brain, skin, fat, kidneys, and muscle of male Sprague-Dawley rats using two
      different analytical methods. The free phase concentration (in phosphate-buffered
      saline) of a given chemical was measured in the presence and absence of tissue
      (including blood) and used to calculate the PC, defined as the ratio of the
      concentration of the chemical in saline to the concentration in the tissue. PCs
      were determined for 13 compounds with aqueous solubility ranging from 20 to 4100
      mg/L, molecular weights from 187.3 to 342.2 g/mol, and log K (ow) values from 
      0.18 to 3.9. An ultrafiltration high-performance liquid chromatography (HPLC)
      method was implemented for compounds with log K (ow) near 0.1 or less and a
      negligible depletion solid-phase microextraction (nd-SPME) method for compounds
      with higher log K (ow). PC(tissue:saline) coefficients of variation were 0.13 (n
      = 3 compounds) on average for the HPLC method and 0.29 (n = 10 compounds) for the
      nd-SPME method. Presented here is one of the most comprehensive data sets of
      biological partition coefficients for herbicides, insecticides, and fungicides.

PMID- 22409492
TI  - Subchronic JP-8 jet fuel exposure enhances vulnerability to noise-induced hearing
      loss in rats.
AB  - Both laboratory and epidemiological studies published over the past two decades
      have identified the risk of excess hearing loss when specific chemical
      contaminants are present along with noise. The objective of this study was to
      evaluate the potency of JP-8 jet fuel to enhance noise-induced hearing loss
      (NIHL) using inhalation exposure to fuel and simultaneous exposure to either
      continuous or intermittent noise exposure over a 4-wk exposure period using both
      male and female Fischer 344 rats. In the initial study, male (n = 5) and female
      (n = 5) rats received inhalation exposure to JP-8 fuel for 6 h/d, 5 d/wk for 4 wk
      at concentrations of 200, 750, or 1500 mg/m3. Parallel groups of rats also
      received nondamaging noise (constant octave band noise at 85 dB(lin)) in
      combination with the fuel, noise alone (75, 85, or 95 dB), or no exposure to fuel
      or noise. Significant concentration-related impairment of auditory function
      measured by distortion product otoacoustic emissions (DPOAE) and compound action
      potential (CAP) threshold was seen in rats exposed to combined JP-8 plus noise
      exposure when JP-8 levels of 1500 mg/m3 were presented with trends toward
      impairment seen with 750 mg/m3 JP-8 + noise. JP-8 alone exerted no significant
      effect on auditory function. In addition, noise was able to disrupt the DPOAE and
      increase auditory thresholds only when noise exposure was at 95 dB. In a
      subsequent study, male (n = 5 per group) and female (n = 5 per group) rats
      received 1000 mg/m3 JP-8 for 6 h/d, 5 d/wk for 4 wk with and without exposure to
      102 dB octave band noise that was present for 15 min out of each hour (total
      noise duration 90 min). Comparisons were made to rats receiving only noise, and
      thosereceiving no experimental treatment. Significant impairment of auditory
      thresholds especially for high-frequency tones was identified in the male rats
      receiving combined treatment. This study provides a basis for estimating
      excessive hearing loss under conditions of subchronic JP-8 jet fuel exposure.

PMID- 22409493
TI  - Deuterium kinetic isotope effects on the dissociation of a protein-fatty acid
      complex in the gas phase.
AB  - Deuterium kinetic isotope effects (KIEs) are reported for the first time for the
      dissociation of a protein-ligand complex in the gas phase. Temperature-dependent
      rate constants were measured for the loss of neutral ligand from the deprotonated
      ions of the 1:1 complex of bovine beta-lactoglobulin (Lg) and palmitic acid (PA),
      (Lg + PA)(n-) -> Lg(n-) + PA, at the 6- and 7- charge states. At 25  degrees C,
      partial or complete deuteration of the acyl chain of PA results in a measurable
      inverse KIE for both charge states. The magnitude of the KIEs is temperature
      dependent, and Arrhenius analysis of the rate constants reveals that deuteration
      of PA results in a decrease in activation energy. In contrast, there is no
      measurable deuterium KIE for the dissociation of the (Lg + PA) complex in aqueous
      solution at pH 8. Deuterium KIEs were calculated using conventional transition
      state theory with an assumption of a late dissociative transition state (TS), in
      which the ligand is free of the binding pocket. The vibrational frequencies of
      deuterated and non-deuterated PA in the gas phase and in various solvents (n
      hexane, 1-chlorohexane, acetone, and water) were established computationally. The
      KIEs calculated from the corresponding differences in zero-point energies account
      qualitatively for the observation of an inverse KIE but do not account for the
      magnitude of the KIEs nor their temperature dependence. It is proposed that the
      dissociation of the (Lg + PA) complex in aqueous solution also proceeds through a
      late TS in which the acyl chain is extensively hydrated such that there is no
      significant differential change in the vibrational frequencies along the reaction
      coordinate and, consequently, no significant KIE.

PMID- 22409495
TI  - Size-dependent cell uptake of protein-coated graphene oxide nanosheets.
AB  - As an emerging applied material, graphene has shown tremendous application
      potential in many fields, including biomedicine. However, the biological behavior
      of these nanosheets, especially their interactions with cells, is not well
      understood. Here, we report our findings about the cell surface adhesion,
      subcellular locations, and size-dependent uptake mechanisms of protein-coated
      graphene oxide nanosheets (PCGO). Small nanosheets enter cells mainly through
      clathrin-mediated endocytosis, and the increase of graphene size enhances
      phagocytotic uptake of the nanosheets. These findings will facilitate biomedical
      and toxicologic studies of graphenes and provide fundamental understanding of
      interactions at the interface of two-dimensional nanostructures and biological
      systems.

PMID- 22409497
TI  - Drugs for Alzheimer's disease.

PMID- 22409499
TI  - Effects of salt and ligand concentrations on the thermal unfolding and refolding
      of halophilic starch-binding domain from Kocuria varians alpha-amylase.
AB  - The starch binding domain of alpha-amlylase from moderate halophile was expressed
      in E. coli with His tag (His- SBD12) and characterized for its halophilic
      properties. His-SBD12 was stable up to 35 degrees C and showed binding activity,
      although at reduced level, to amylose even in the absence of NaCl. Both NaCl and
      specific ligands exhibited insignificant influence on the secondary structure of
      His-SBD12, but showed significant stabilization effects against thermal unfolding
      concentration-dependently, showing its halophilic properties. NaCl increased
      thermal stability of His-SBD12 by 4 degrees C at 0.2 M and 15 degrees C at 2 M,
      and enhanced refolding rate by ~7-fold at 0.2 M and ~170-fold at 2 M. Its
      specific ligands, beta- cyclodextrin (at 3 mM) and maltose (at 470 mM), also
      stabilized the protein by 11 degrees  C, most likely reflecting affinity
      difference between these two ligands. However, they showed marginal effects on
      refolding rate. These observations suggest that although binding of NaCl and
      specific ligands to the native structure can explain their stabilization effects
      on His- SBD12, it is not a sole factor for modulating their effects on folding of
      His-SBD12.

PMID- 22409500
TI  - Properties of a putative cambialistic superoxide dismutase from the aerotolerant
      bacterium Streptococcus thermophilus strain LMG 18311.
AB  - The aerotolerance of the lactic - fermentative bacterium Streptococcus
      thermophilus is mainly based on the key antioxidant function of superoxide
      dismutase (StSOD). In this work, the comparison of recombinant StSOD (rStSOD)
      forms obtained from two different initiation triplets indicated that the enzyme
      from S. thermophilus strain LMG 18311 spans 201 residues. rStSOD is organised as
      a homodimer, even though protein aggregates are formed in concentrated solutions.
      The capability of binding and exchanging Fe or Mn in the active site classifies
      rStSOD as a putative cambialistic enzyme; the moderate preference for iron is
      counteracted by a 1.5-fold higher activity measured for the Mn-containing form.
      The enzyme is thermostable, being its half-inactivation time 10 min at 73.5
      degrees C; the energetic parameters of the heat inactivation process are
      regulated by the level of Mn cofactor. The effect of Mn content on the rStSOD
      sensitivity towards inhibitors and inactivators was also evaluated. Sodium azide
      acts as a weak inhibitor of rStSOD and its Mn content does not greatly affect
      this sensitivity. Concerning the physiological inactivator hydrogen peroxide, the
      Mn-enriched rStSOD displays a great resistance; a moderate sensitivity is instead
      observed in the presence of a low Mn content. Contrary to hydrogen peroxide,
      sodium peroxynitrite is a powerful inactivator, a behaviour enhanced in the Mn
      enriched enzyme. All these results were compared with the corresponding data
      previously reported for the cambialistic SOD from the taxonomically related S.
      mutans. In S. thermophilus the regulation of the enzyme functions by the Mn
      content appears less relevant with respect to S. mutans.

PMID- 22409501
TI  - Sequence preference of alpha-helix N-terminal tetrapeptide.
AB  - The alpha-helix is the most abundant secondary structure in proteins. Due to the
      specific i, i+4 hydrogen bond pattern, the two termini have unsatisfied hydrogen
      bonds, and are less constrained; in order to compensate for this, specific
      residues are preferred for the terminal positions. However, a naive combination
      of the statistically-preferred residues for each position may not result in a
      stable N-terminal helical sequence. In order to provide a set of preferable N
      terminal peptides for alpha-helix design, we have studied the N-terminal
      tetrapeptide sequence motifs that are favorable for helix formation using
      statistical analysis and atomistic simulations. A set of tetrapeptide sequences
      including TEEE and TPEE were found to be favorable motifs. In addition to forming
      more hydrogen bonds in the helical conformation, the favorable motifs also tended
      to form more capping boxes. To empirically test our predictions, we obtained 10
      peptides with different N-terminal motifs and measured their alpha-helical
      content by circular dichroism spectroscopy. The experimental results agreed
      qualitatively with the statistical and simulation results. Furthermore, some of
      the suggested preferable tetrapeptide sequences have been successfully applied in
      de novo protein design.

PMID- 22409502
TI  - The role of bactericidal/permeability-increasing protein in men with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND AND OBJECTIVE: Bactericidal/permeability-increasing protein (BPI) is a
      member of the pattern recognition receptors of the innate immune system.
      Recently, an association between genetic polymorphism in the BPI gene and a risk
      of airflow decline after transplantation was demonstrated, but whether these
      findings are reproducible in nontransplantation populations, such as those with
      COPD, is still unknown. The aim of this study is to explore the role of BPI in
      COPD. METHODS: The genotypes of 107 patients with COPD and 110 control subjects
      were evaluated by polymerase chain reaction and polymorphism analysis of the BPI
      genes and ELISA analysis of the plasma BPI level. All subjects were men over 40
      years old who smoked. RESULTS: BPI mutation PstI (T->C) polymorphism in intron 5
      was associated with an increased risk of developing COPD (OR 3.73, 95%CI: 1.62
      9.10), and the frequency was significantly increased in the COPD group compared
      with the control group (26/107 [24.3%] vs 12/110 [10.9%], p = 0.002). In
      addition, COPD patients exhibited a decreased plasma level of BPI compared with
      the control group (10.6 +/- 2.2 vs 23.4 +/- 2.1 ng/ml, p < 0.0001). CONCLUSIONS:
      BPI mutation (PstI in intron 5) and a decreased plasma BPI level were significant
      risk factors in susceptibility to COPD. These results demonstrate that BPI
      genetic mutation and impaired BPI production or release may result in airflow
      obstruction in smokers.

PMID- 22409503
TI  - What determines the sign reversal of magnetoresistance in a molecular tunnel
      junction?
AB  - The observations of both positive and negative signs in tunneling
      magnetoresistance (TMR) for the same organic spin-valve structure have baffled
      researchers working in organic spintronics. In this article, we provide an answer
      to this puzzle by exploring the role of metal-molecule interface on TMR in a
      single molecular spin-valve junction. A planar organic molecule sandwiched
      between two nickel electrodes is used to build a prototypical spin-valve
      junction. A parameter-free, single-particle Green's function approach in
      conjunction with a posteriori, spin-unrestricted density functional theory
      involving a hybrid orbital-dependent functional is used to calculate the spin
      polarized current. The effect of external bias is explicitly included to
      investigate the spin-valve behavior. Our calculations show that only a small
      change in the interfacial distance at the metal-molecule junction can alter the
      sign of the TMR from a positive to a negative value. By changing the interfacial
      distance by 3%, the number of participating eigenchannels as well as their
      orbital characteristics changes for the antiparallel configuration, leading to
      the sign reversal in TMR.

PMID- 22409504
TI  - Energetic study applied to the knowledge of the structural and electronic
      properties of monofluorobenzonitriles.
AB  - The present work reports an energetic and structural study of 2-fluoro-, 3-fluoro
      , and 4-fluorobenzonitrile. The standard molar enthalpies of formation, in the
      condensed phase, of the three isomers were derived from the standard molar
      energies of combustion, in oxygen, at T = 298.15 K. The standard molar enthalpies
      of vaporization or sublimation (for 4-fluorobenzonitrile), at T = 298.15 K, were
      measured using high-temperature Calvet microcalorimetry. The combination of these
      two parameters yields the standard molar enthalpies of formation in the gaseous
      phase. The vapor-pressure study of the referred compounds was performed by a
      static method, and the enthalpies of phase transition derived from the
      application of the Clarke and Glew equation. Theoretically estimated gas-phase
      enthalpies of formation, basicities, proton and electron affinities, and
      adiabatic ionization enthalpies were calculated from the G3MP2B3 level of theory.
      In order to evaluate the electronic properties, the geometries were reoptimized
      at MP2/cc-pVTZ level, and the QTAIM and NICS were computed. On the basis of the
      donor-acceptor system, another approach for evaluating the electronic effect for
      these compounds, using the NBO is suggested. The UV-vis spectroscopy study for
      the three isomers was performed. The intensities and the band positions were
      correlated with the thermodynamic properties calculated computationally.

PMID- 22409505
TI  - Evaluation of the evidence for the trauma and fantasy models of dissociation.
AB  - The relationship between a reported history of trauma and dissociative symptoms
      has been explained in 2 conflicting ways. Pathological dissociation has been
      conceptualized as a response to antecedent traumatic stress and/or severe
      psychological adversity. Others have proposed that dissociation makes individuals
      prone to fantasy, thereby engendering confabulated memories of trauma. We examine
      data related to a series of 8 contrasting predictions based on the trauma model
      and the fantasy model of dissociation. In keeping with the trauma model, the
      relationship between trauma and dissociation was consistent and moderate in
      strength, and remained significant when objective measures of trauma were used.
      Dissociation was temporally related to trauma and trauma treatment, and was
      predictive of trauma history when fantasy proneness was controlled. Dissociation
      was not reliably associated with suggestibility, nor was there evidence for the
      fantasy model prediction of greater inaccuracy of recovered memory. Instead,
      dissociation was positively related to a history of trauma memory recovery and
      negatively related to the more general measures of narrative cohesion. Research
      also supports the trauma theory of dissociation as a regulatory response to fear
      or other extreme emotion with measurable biological correlates. We conclude, on
      the basis of evidence related to these 8 predictions, that there is strong
      empirical support for the hypothesis that trauma causes dissociation, and that
      dissociation remains related to trauma history when fantasy proneness is
      controlled. We find little support for the hypothesis that the dissociation
      trauma relationship is due to fantasy proneness or confabulated memories of
      trauma.

PMID- 22409506
TI  - Rewards and creative performance: a meta-analytic test of theoretically derived
      hypotheses.
AB  - Although many scholars and practitioners are interested in understanding how to
      motivate individuals to be more creative, whether and how rewards affect
      creativity remain unclear. We argue that the conflicting evidence may be due to
      differences between studies in terms of reward conditions and the context in
      which rewards are offered. Specifically, we examine 5 potential moderators of the
      rewards-creative performance relationship: (a) the reward contingency, (b) the
      extent to which participants are provided information about their past or current
      creative performance, (c) the extent to which the reward and context offer choice
      or impose control, (d) the extent to which the context serves to enhance task
      engagement, and (e) the extent to which the performance tasks are complex. Using
      random-effects models, we meta-analyzed 60 experimental and nonexperimental
      studies (including 69 independent samples) that examined the rewards-creativity
      relationship with children or adults. Our results suggest that creativity
      contingent rewards tend to increase creative performance-and are more positively
      related to creative performance when individuals are given more positive,
      contingent, and task-focused performance feedback and are provided more choice
      (and are less controlled). In contrast, performance-contingent or completion
      contingent rewards tend to have a slight negative effect on creative performance.

PMID- 22409507
TI  - Memory in autistic spectrum disorder.
AB  - Behavioral evidence concerning memory in forms of high-functioning autism (HFA)
      and in moderately low-functioning autism (M-LFA) is reviewed and compared.
      Findings on M-LFA are sparse. However, it is provisionally concluded that memory
      profiles in HFA and M-LFA (relative to ability-matched controls) are similar but
      that declarative memory impairments are more extensive in M-LFA than in HFA.
      Specifically, both groups have diminished memory for emotion- or person-related
      stimuli. Regarding memory for nonsocial stimuli, both groups probably have mental
      age-appropriate nondeclarative memory, and within declarative memory, both groups
      have mental-age-appropriate immediate free recall of within-span or supraspan
      lists of unrelated items, as well as cued recall and paired associate learning.
      By contrast, recognition is largely unimpaired in HFA but moderately impaired in
      M-LFA, and free recall of meaningful or structured stimuli is moderately impaired
      in HFA but more severely impaired in M-LFA. Theoretical explanations of data on
      declarative memory in HFA identify problems in the integrative processing, or the
      consolidation and storage, of complex stimuli or a specific problem of
      recollection. Proposed neural substrates include the following: disconnectivity
      of primary sensory and association areas; dysfunctions of medial prefrontal
      cortex, hippocampus, or posterior parietal lobe; or combinations of these
      associated with neural disconnectivity. Hypothetically, perirhinal dysfunction
      might explain the more extensive declarative memory impairments in M-LFA.
      Foreseeable consequences of uneven memory abilities in HFA and M-LFA are
      outlined, including possible effects on language and learning in M-LFA. Finally,
      priorities for future research are identified, highlighting the urgent need for
      research on memory in lower functioning individuals.

PMID- 22409508
TI  - Is working memory training effective?
AB  - Working memory (WM) is a cognitive system that strongly relates to a person's
      ability to reason with novel information and direct attention to goal-relevant
      information. Due to the central role that WM plays in general cognition, it has
      become the focus of a rapidly growing training literature that seeks to affect
      broad cognitive change through prolonged training on WM tasks. Recent work has
      suggested that the effects of WM training extend to general fluid intelligence,
      attentional control, and reductions in symptoms of ADHD. We present a
      theoretically motivated perspective of WM and subsequently review the WM training
      literature in light of several concerns. These include (a) the tendency for
      researchers to define change to abilities using single tasks, (b) inconsistent
      use of valid WM tasks, (c) no-contact control groups, and (d) subjective
      measurement of change. The literature review highlights several findings that
      warrant further research but ultimately concludes that there is a need to
      directly demonstrate that WM capacity increases in response to training.
      Specifically, we argue that transfer of training to WM must be demonstrated using
      a wider variety of tasks, thus eliminating the possibility that results can be
      explained by task specific learning. Additionally, we express concern that many
      of the most promising results (e.g., increased intelligence) cannot be readily
      attributed to changes in WM capacity. Thus, a critical goal for future research
      is to uncover the mechanisms that lead to transfer of training.

PMID- 22409509
TI  - Hematology and enzyme histochemistry of peripheral blood lymphocytes in domestic
      pigeon (Columba livia f. domestica).
AB  - The purpose of our study was to determine the percentages of alpha-naphthyl
      acetate esterase (ANAE)-positive and acid phosphatase (ACP)-positive peripheral
      blood lymphocytes (PBL) in both sexes of one-year-old domestic pigeons (Columba
      livia f. domestica). Blood samples obtained from 12 healthy domestic pigeons were
      used. The mean percentages of ANAE-positive PBL for females and males were 47.8%
      and 48.8%, respectively, whereas the mean percentages of ACP-positive PBL were
      67.5% and 68.6%, respectively. The proportions of PBL were 49.3% and 48.6% in
      males and females, respectively.

PMID- 22409510
TI  - Enantioselective synthesis of (+)-crocacin C. An example of a highly challenging
      mismatched double asymmetric delta-stannylcrotylboration reaction.
AB  - A concise, enantioselective synthesis of (+)-crocacin C is described, featuring a
      highly diastereoselective mismatched double asymmetric delta
      stannylcrotylboration of the stereochemically demanding chiral aldehyde 9 with
      the bifunctional crotylborane reagent (S)-E-10. The total synthesis of (+)
      crocacin C was accomplished in seven steps (longest linear sequence) starting
      from commercially available precursors.

PMID- 22409511
TI  - A comparative analysis of the attachment of Leptospira interrogans and L.
      borgpetersenii to mammalian cells.
AB  - Leptospirosis, the world's most ubiquitous zoonosis, is caused by pathogenic
      Leptospira. As microbe-host interactions are specific in pathogenesis, it is
      likely that there are several molecules mediating the attachment of the
      Leptospira to mammalian cells. In this study, we analysed the attachment of
      Leptospira interrogans serovar Portlandvere and Leptospira borgpetersenii serovar
      Jules to untreated HEp-2 cells or HEp-2 cells treated with the various enzymes,
      lectins or sugars and to integrins alphaVbeta3 and alpha5beta1, relative to
      control wells. We found that both serovars bound equally well to HEp-2 cells;
      however, serovar Jules showed a higher level of attachment to integrins. Both
      serovars showed an increase in attachment to HEp-2 cells coated with lectins
      peanut agglutinin, Ulex europaeus agglutinin, soybean agglutinin and Erythrina
      cristagalli agglutinin (p < 0.05); in the case of Concanavalin A, Jules showed an
      increase, while Portlandvere showed a significant decrease in attachment.
      Trypsinizing monolayers resulted in a decrease in attachment for both serovars,
      while when chondroitinase, neuraminidase and heparinase were used an increase in
      attachment was recorded. Leptospires coated with sugars showed a decrease in
      attachment. These results show that serovar Jules' general greater affinity for
      the mediators examined may suggest a greater potential for virulence over serovar
      Portlandvere.

PMID- 22409512
TI  - Behavioral plasticity in honey bees is associated with differences in brain
      microRNA transcriptome.
AB  - Small, non-coding microRNAs (miRNAs) have been implicated in many biological
      processes, including the development of the nervous system. However, the roles of
      miRNAs in natural behavioral and neuronal plasticity are not well understood. To
      help address this we characterized the microRNA transcriptome in the adult worker
      honey bee head and investigated whether changes in microRNA expression levels in
      the brain are associated with division of labor among honey bees, a well
      established model for socially regulated behavior. We determined that several
      miRNAs were downregulated in bees that specialize on brood care (nurses) relative
      to foragers. Additional experiments showed that this downregulation is dependent
      upon social context; it only occurred when nurse bees were in colonies that also
      contained foragers. Analyses of conservation patterns of brain-expressed miRNAs
      across Hymenoptera suggest a role for certain miRNAs in the evolution of the
      Aculeata, which includes all the eusocial hymenopteran species. Our results
      support the intriguing hypothesis that miRNAs are important regulators of social
      behavior at both developmental and evolutionary time scales.

PMID- 22409514
TI  - Medical and endoscopic management of high-grade dysplasia in Barrett's esophagus.
AB  - The management of high-grade dysplasia in Barrett's esophagus has clearly changed
      over recent years. The risk of cancer development is still substantial, with
      about one in three patients developing cancer, but a number of patients do not
      develop cancer. The nature of high-grade dysplasia has also been genetically
      elucidated with more evidence of chromosomal instability being present at this
      stage than previously thought. Therapy of the condition has evolved more toward
      endoscopic therapy, given the good results of radio-frequency ablation and
      photodynamic therapy in eliminating dysplasia and decreasing cancer development
      in randomized controlled trial. The best candidates for treatment include
      compliant patients that have relatively short segments of Barrett's esophagus, an
      anatomically straight segment, lack of nodularity, and an intact p16. However,
      even with excellent long-term results similar to surgical resection, the risk of
      recurrence is present in over 14% of patients, which indicates that there will be
      a need to continue surveillance endoscopy in these patients.

PMID- 22409515
TI  - Flowering time and transcriptome variation in Capsella bursa-pastoris
      (Brassicaceae).
AB  - * Flowering is a major developmental transition and its timing in relation to
      environmental conditions is of crucial importance to plant fitness. Understanding
      the genetic basis of flowering time variation is important to determining how
      plants adapt locally. * Here, we investigated flowering time variation of
      Capsella bursa-pastoris collected from different latitudes in China. We also used
      a digital gene expression (DGE) system to generate partial gene expression
      profiles for 12 selected samples. * We found that flowering time was highly
      variable and most strongly correlated with day length and winter temperature.
      Significant differences in gene expression between early- and late-flowering
      samples were detected for 72 candidate genes for flowering time. Genes related to
      circadian rhythms were significantly overrepresented among the differentially
      expressed genes. * Our data suggest that circadian rhythms and circadian clock
      genes play an important role in the evolution of flowering time, and C. bursa
      pastoris plants exhibit expression differences for candidate genes likely to
      affect flowering time across the broad range of environments they face in China.

PMID- 22409517
TI  - The viral aetiology of diabetes: a tribute to Keith Taylor (1929-2012).

PMID- 22409518
TI  - Can epigenetic control explain pronounced within-plant heterogeneity of meiosis
      in a translocation trisome of Secale L.?
AB  - Meiotic metaphase I configuration frequencies were determined in different
      tillers of genetically related plants of rye ( Secale cereale  L.) heterozygous
      for reciprocal translocation T248W (between chromosome arms 1RS and 6RS) and with
      an additional (telocentric) arm 1RS. Seventeen different configurations could be
      recognized, grouped into three categories. Very different configuration
      frequencies were found not only between sister plants from the same parents but
      also between tillers of the same plant grown under identical conditions (climate
      chambers at 15  degrees C and 20  degrees C). The heterogeneity reflects
      variation in chromosome pairing and crossing over, and is variable and
      unpredictable. Anthers within florets were homogeneous. Between tiller
      heterogeneity is insufficient to explain differences between sister plants. It is
      ascribed to random somatic variation in the conditions of the chromatin which, at
      meiosis, govern chromosome pairing. During sexual differentiation, these
      conditions are fixed and subsequent cell lineages have the same pairing and
      crossing over characteristics. As homology search is an activity of DNA, this
      control of pairing and crossing over, consistent over long cell lineages, may be
      considered to be epigenetic even when no realistic suggestions concerning its
      character can be given.

PMID- 22409516
TI  - Genome sequencing of ovine isolates of Mycobacterium avium subspecies
      paratuberculosis offers insights into host association.
AB  - BACKGROUND: The genome of Mycobacterium avium subspecies paratuberculosis (MAP)
      is remarkably homogeneous among the genomes of bovine, human and wildlife
      isolates. However, previous work in our laboratories with the bovine K-10 strain
      has revealed substantial differences compared to sheep isolates. To
      systematically characterize all genomic differences that may be associated with
      the specific hosts, we sequenced the genomes of three U.S. sheep isolates and
      also obtained an optical map. RESULTS: Our analysis of one of the isolates, MAP
      S397, revealed a genome 4.8 Mb in size with 4,700 open reading frames (ORFs).
      Comparative analysis of the MAP S397 isolate showed it acquired approximately 10
      large sequence regions that are shared with the human M. avium subsp. hominissuis
      strain 104 and lost 2 large regions that are present in the bovine strain. In
      addition, optical mapping defined the presence of 7 large inversions between the
      bovine and ovine genomes (~ 2.36 Mb). Whole-genome sequencing of 2 additional
      sheep strains of MAP (JTC1074 and JTC7565) further confirmed genomic homogeneity
      of the sheep isolates despite the presence of polymorphisms on the nucleotide
      level. CONCLUSIONS: Comparative sequence analysis employed here provided a better
      understanding of the host association, evolution of members of the M. avium
      complex and could help in deciphering the phenotypic differences observed among
      sheep and cattle strains of MAP. A similar approach based on whole-genome
      sequencing combined with optical mapping could be employed to examine closely
      related pathogens. We propose an evolutionary scenario for M. avium complex
      strains based on these genome sequences.

PMID- 22409519
TI  - Observation of a tungsten alkane sigma-complex showing selective binding of
      methyl groups using FTIR and NMR spectroscopies.
AB  - The alkane sigma-complex (HEB)W(CO)(2)(pentane) (HEB = eta(6)-hexaethylbenzene)
      is produced from the UV photolysis of (HEB)W(CO)(3) in alkane solvents at low
      temperature. IR and (1)H and (13)C NMR spectroscopic data are reported,
      representing the first NMR data for a group 6 alkane complex. Only binding of the
      methyl functionality of the pentane ligand was observed in
      (HEB)W(CO)(2)(pentane). This contrasts with the previously reported binding of
      pentane to rhenium fragments, wherein both methylene and methyl groups were
      observed to bind, with a slight preference for binding of the former. The reason
      for the preference for binding through the methyl group is investigated, and the
      steric requirement for the pentane to adopt an unfavorable gauche conformation
      when bound via a methylene is identified as a contributing factor.

PMID- 22409520
TI  - Acral histiocytic nodules: a possible new variant of non-X histiocytosis.
AB  - Many types of histiocytoses have been described. We present a case of a 56-year
      old woman who presented with multiple nodules on the hands. On histological
      examination of an excision biopsy, a mainly dermal lesion was seen, with
      scattered mononuclear inflammatory cells and occasional multinucleated cells in
      the background. The tumour was composed of short spindle-shaped histiocyte-like
      cells with vesicular nuclei and small nucleoli. These cells were positive for
      CD68 and focally positive for smooth-muscle actin. There was no lipid or
      haemosiderin pigment, and no cholesterol clefts. Further investigations did not
      find evidence of bony or systemic involvement. The non-Langerhans cell
      histiocytoses, also known as non-X histiocytoses, are rare and of unknown
      aetiology. Clinicopathologically, this case does not seem to fit with any of the
      recognized subtypes, and we propose that it may represent a previously
      undescribed variant of the disease.

PMID- 22409521
TI  - An unusual presentation of juvenile systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a multisystem disorder with a diverse
      spectrum of clinical abnormality. Despite advances in our understanding of the
      disease, the aetiology and outcome remains unknown. We describe a 13-year-old boy
      who presented with paronychia, mouth ulcers and associated neutropenia.
      Appropriate investigations including a bone-marrow biopsy revealed a shift to the
      left, and in the absence of any other immunological abnormalities, a diagnosis of
      idiopathic neutropenia was made. The patient was successfully treated with
      granulocyte colony-stimulating factor but subsequently re-presented during the
      winter months with a purpuric facial eruption affecting his cheeks and ears. On
      histological examination of a biopsy taken from the ear, a microvascular
      thrombosis was seen. Laboratory investigations were positive for anticardiolipin
      antibodies, neutropenia and antinuclear antibodies (ANA), suggesting a diagnosis
      of juvenile (J)JSLE with antiphospholipid syndrome. This is an unusual
      presentation of SLE in a prepubertal white boy, with a malar and helical
      vasculopathy as a novel cutaneous presentation of JSLE.

PMID- 22409522
TI  - Increased halogenated tyrosine levels are useful markers of human skin ageing,
      reflecting proteins denatured by past skin inflammation.
AB  - BACKGROUND: Photoageing of skin is thought to be caused by protein denaturation,
      which can be induced by ultraviolet radiation. Previous studies have also
      reported that inflammation is related to protein denaturation; however, the
      influence of inflammation on skin ageing has not been explored in detail. AIM: To
      investigate the possible connection between inflammation and protein
      denaturation, which might lead to skin ageing, we focused on halogenated tyrosine
      as a denatured substance produced during the inflammation process. METHODS: We
      measured halogenated tyrosine in aged human skin. Inflammatory cells and
      halogenated tyrosine were detected by immunohistochemistry using antibodies to
      mast-cell tryptase, neutrophilic myeloperoxidase and halogenated tyrosine.
      Finally, using elastic van Gieson (EVG) staining, we investigated whether the
      sites of halogenated tyrosine coincided with the sites at which proteins were
      denatured. RESULTS: Immunohistochemical analysis indicated that both inflammatory
      cells and halogenated tyrosines increased with ageing in both photoexposed and
      photoprotected skin. EVG staining confirmed that the localization of halogenated
      tyrosine was close to the sites at which protein was denatured. CONCLUSIONS: Our
      investigations indicate a possible connection between skin ageing and
      inflammation, suggesting that halogenated tyrosine could be a useful marker of
      ageing skin.

PMID- 22409524
TI  - Topical photodynamic therapy with 5-aminolaevulinic acid for condylomata
      acuminata on the distal urethra.

PMID- 22409523
TI  - A novel rat model for chemotherapy-induced alopecia.
AB  - BACKGROUND: More than half of all people diagnosed with cancer receive
      chemotherapy, and approximately 65% of these develop chemotherapy-induced
      alopecia (CIA), a side-effect that can have considerable negative psychological
      repercussions. Currently, there are very few animal models available to study the
      mechanism and prevention of CIA. AIM: To develop a clinically relevant adult rat
      model for CIA. METHODS: We first tested whether neonatal pigmented Long-Evans
      (LE) rats developed alopecia in response to the chemotherapeutic agents etoposide
      and cyclophosphamide. We then determined whether the rats developed CIA as
      adults. In the latter experiment, rat dorsal hair was clipped during the early
      telogen stage to synchronize the hair cycle, and starting 15 days later, the rats
      were treated with etoposide for 3 days. RESULTS: Neonatal LE pups developed CIA
      in response to etoposide and cyclophosphamide, similar to other murine models for
      CIA. Clipping of the hair shaft during early telogen resulted in synchronized
      anagen induction and subsequent alopecia after etoposide treatment in the clipped
      areas only. Hair follicles in the clipped areas had the typical chemotherapy
      induced follicular dystrophy (dystrophic catagen). When the hair in the pigmented
      alopecic areas regrew, it had normal pigmentation. CONCLUSIONS: A novel,
      pigmented adult rat model has been established for CIA. By hair-shaft clipping
      during early telogen, synchronized anagen entry was induced, which resulted in
      alopecia in response to chemotherapy. This is the first clinically relevant adult
      rat model for CIA, and will be a useful tool to test agents for the prevention
      and treatment of CIA.

PMID- 22409525
TI  - Asymptomatic whitish papules over both arms in a 28-year-old woman.

PMID- 22409526
TI  - Premature wrinkling of the skin in a 31-year-old woman.

PMID- 22409527
TI  - Asymptomatic patches on the shoulder and upper trunk.

PMID- 22409528
TI  - The different faces of actinomycosis.

PMID- 22409529
TI  - An electrochemically reduced graphene oxide-based electrochemical immunosensing
      platform for ultrasensitive antigen detection.
AB  - We present an electrochemically reduced graphene oxide (ERGO)-based
      electrochemical immunosensing platform for the ultrasensitive detection of an
      antigen by the sandwich enzyme-linked immunosorbent assay (ELISA) protocol.
      Graphene oxide (GO) sheets were initially deposited on the amine-terminated
      benzenediazonium-modified indiun tin oxide (ITO) surfaces through both
      electrostatic and pi-pi interactions between the modified surfaces and GO. This
      deposition was followed by the electrochemical reduction of graphene oxide (GO)
      for preparing ERGO-modified ITO surfaces. These surfaces were then coated with an
      N-acryloxysuccinimide-activated amphiphilic polymer, poly(BMA-r-PEGMA-r-NAS),
      through pi-pi stacking interactions between the benzene ring tethered to the
      polymer and ERGO. After covalent immobilization of a primary antibody on the
      polymer-modified surfaces, sandwich ELISA was carried out for the detection of an
      antigen by use of a horseradish peroxidase (HRP)-labeled secondary antibody.
      Under the optimized experimental conditions, the developed electrochemical
      immunosensor exhibited a linear response over a wide range of antigen
      concentrations with a very low limit of detection (ca. 100 fg/mL, which
      corresponds to ca. 700 aM). The high sensitivity of the electrochemical
      immunosensor may be attributed not only to the enhanced electrocatalytic activity
      owing to ERGO but also to the minimized background current owing to the reduced
      nonspecific binding of proteins.

PMID- 22409530
TI  - Evaluation of coupling reversed phase, aqueous normal phase, and hydrophilic
      interaction liquid chromatography with Orbitrap mass spectrometry for metabolomic
      studies of human urine.
AB  - In this study, we assessed three liquid chromatographic platforms: reversed phase
      (RP), aqueous normal phase (ANP), and hydrophilic interaction (HILIC) for the
      analysis of polar metabolite standard mixtures and for their coverage of urinary
      metabolites. The two zwitterionic HILIC columns showed high-quality
      chromatographic performance for metabolite standards, improved separation for
      isomers, and the greatest coverage of polar metabolites in urine. In contrast, on
      the reversed phase column, most metabolites eluted very rapidly with little or no
      separation. Using an Exactive Orbitrap mass spectrometer with a HILIC liquid
      chromatographic platform, approximately 970 metabolite signals with repeatable
      peak areas (relative standard deviation (RSD) <= 25%) could be putatively
      identified in human urine, by elemental composition assignment within a 3 ppm
      mass error. The ability of the methodology for the verification of nonmolecular
      ions, which arise from adduct formation, and the possibility of distinguishing
      isomers could also be demonstrated. Careful examination of the raw data and the
      use of masses for predicted metabolites produced an extension of the metabolite
      list for human urine.

PMID- 22409531
TI  - Drug-induced alterations in Mg2+ homoeostasis.
AB  - Magnesium (Mg2+) balance is tightly regulated by the concerted actions of the
      intestine, bone and kidneys. This balance can be disturbed by a broad variety of
      drugs. Diuretics, modulators of the EGFR (epidermal growth factor receptor),
      proton pump inhibitors, antimicrobials, calcineurin inhibitors and cytostatics
      may all cause hypomagnesaemia, potentially leading to tetany, seizures and
      cardiac arrhythmias. Conversely, high doses of Mg2+ salts, frequently
      administered as an antacid or a laxative, may lead to hypermagnesaemia causing
      various cardiovascular and neuromuscular abnormalities. A better understanding of
      the molecular mechanisms underlying the adverse effects of these medications on
      Mg2+ balance will indicate ways of prevention and treatment of these adverse
      effects and could potentially provide more insight into Mg2+ homoeostasis.

PMID- 22409532
TI  - Early return visits by primary care patients: a retail nurse practitioner clinic
      versus standard medical office care.
AB  - The purpose of this study was to compare return visits made by patients within 2
      weeks after using retail nurse practitioner clinics to return visits made by
      similar patients after using standard medical office clinics. Retail medicine
      clinics have become widely available. However, their impact on return visit rates
      compared to standard medical office visits for similar patients has not been
      extensively studied. Electronic medical records of adult primary care patients
      seen in a large group practice in Minnesota in 2009 were analyzed for this study.
      Patients who were treated for sinusitis were selected. Two groups of patients
      were studied: those who used one of 2 retail walk-in clinics staffed by nurse
      practitioners and a comparison group who used one of 4 regular office clinics.
      The dependent variable was a return office visit to any site within 2 weeks.
      Multiple logistic regression analysis was used to adjust for case-mix differences
      between groups. Unadjusted odds of return visits were lower for retail clinic
      patients than for standard office care patients. After adjustment for case mix,
      patients with more outpatient visits in the previous 6 months had higher odds of
      return visits within 2 weeks (2-6 prior visits: odds ratio [OR]=1.99, P=0.00; 6
      or more prior visits: OR=6.80, P=0.00). The odds of a return visit within 2 weeks
      were not different by clinic type after adjusting for propensity to use services
      (OR=1.17, P=0.28). After adjusting for case mix differences, return visit rates
      did not differ by clinic type.

PMID- 22409533
TI  - Hydrothermal synthesis and crystal structure of two new hydrated alkaline earth
      metal borates Sr3B6O11(OH)2 and Ba3B6O11(OH)2.
AB  - Two new hydrated borates Sr(3)B(6)O(11)(OH)(2) (1) and Ba(3)B(6)O(11)(OH)(2) (2)
      were hydrothermally synthesized. Their structures were determined by single
      crystal X-ray diffraction and further characterized by IR, powder XRD, and
      DSC/TGA. Compound 1 crystallizes in the triclinic space group P-1 with unit cell
      parameters of a = 6.6275(13) A, b = 6.6706(13) A, c = 11.393(2) A, alpha =
      91.06(3) degrees , beta = 94.50(3) degrees , and gamma = 93.12(3) degrees , while
      compound 2 crystallizes in the noncentrosymmetric monoclinic space group Pc with
      a = 6.958(14) A, b = 7.024(14) A, c = 11.346(2) A, and beta = 90.10(3) degrees .
      In spite of the differences in symmetry and packing of the borate chains, both
      structures consist of the same fundamental building block (FBB) of a
      [B(6)O(11)(OH)(2)](-6) unit and three unique alkaline earth metal atoms.

PMID- 22409534
TI  - Phenotyping COPD using high resolution CT. Is it time to leave it for Watson?

PMID- 22409535
TI  - The complex role of the serotonin transporter in adult neurogenesis and
      neuroplasticity. A critical review.
AB  - OBJECTIVES: Studies on the serotonin transporter (SERT) with regard to
      neurogenesis and neuroplastic effects on the adult brain are scarce. This is
      intriguing since neurogenesis is believed to play a decisive role in modulating
      the effect of selective serotonin reuptake inhibitors (SSRI), which are targeting
      SERT. METHODS: Therefore, we reviewed the current scientific literature about the
      influence of serotonin on neurogenesis with particular emphasis on SERT in
      various settings, both in vivo and in vitro. RESULTS: Experiments using SERT KO
      (knock-out) animal models showed that SERT does not directly or indirectly
      influence neurogenesis in vitro, whereas compensatory mechanism seem to
      participate in vivo. CONCLUSION: At least with regard to adult neural stem cells,
      the impact of serotonin (5-HT) on neuroplasticity and neurogenesis is not due to
      SERT-mediated effcts. Instead, serotonergic fine-tuning may be exerted by a
      number of other different mechanisms including endogenous production of 5-HT in
      adult neural stem cells, uptake of 5-HT into adult neural stem cells by other
      monoamine transporters, and actions of the 5-HT1A receptors present on these
      cells.

PMID- 22409536
TI  - Accessibility, standards and challenges of electroconvulsive therapy in Western
      industrialized countries: a German example.
AB  - OBJECTIVES: The aim of the study was to document the present situation of
      electroconvulsive therapy (ECT) in Germany, compare its handling with regard to
      other industrialized countries and with regard to a survey 12 years ago. METHODS:
      A questionnaire on the frequency and type of administration of ECT in 2008 was
      sent electronically to 423 psychiatric hospitals. As needed, up to five reminders
      were carried out by telephone. On this occasion, the question of whether ECT is
      administered, could be clarified for each hospital. RESULTS: A total of 43%
      (183/423) of hospitals declared to administer ECT; 63% (115/183) reported nearly
      20,000 treatments. A total incidence of 30,000 treatments performed on 2800
      individual patients was estimated. This means that 3.4 patients per 10(5)
      inhabitants, 0.40/00 of all depressed patients, and about 1% of depressed
      inpatients, are treated with ECT in Germany. CONCLUSIONS: The frequency of
      application has increased during the last 12 years by a factor of more than 2.5
      in Germany. In Western industrialized countries, numbers vary by a factor of more
      than 10 amongst the countries with a slow trend of equalization. The mode of
      implementation and the areas of conflict in which the therapy stands seem to be
      similar.

PMID- 22409537
TI  - Rice LGD1 containing RNA binding activity affects growth and development through
      alternative promoters.
AB  - Tiller initiation and panicle development are important agronomical traits for
      grain production in Oryza sativa L. (rice), but their regulatory mechanisms are
      not yet fully understood. In this study, T-DNA mutant and RNAi transgenic
      approaches were used to functionally characterize a unique rice gene, LAGGING
      GROWTH AND DEVELOPMENT 1 (LGD1). The lgd1 mutant showed slow growth, reduced
      tiller number and plant height, altered panicle architecture and reduced grain
      yield. The fewer unelongated internodes and cells in lgd1 led to respective
      reductions in tiller number and to semi-dwarfism. Several independent LGD1-RNAi
      lines exhibited defective phenotypes similar to those observed in lgd1.
      Interestingly, LGD1 encodes multiple transcripts with different transcription
      start sites (TSSs), which were validated by RNA ligase-mediated rapid
      amplification of 5' and 3' cDNA ends (RLM-RACE). Additionally, GUS assays and a
      luciferase promoter assay confirmed the promoter activities of LGD1.1 and LGD1.5.
      LGD1 encoding a von Willebrand factor type A (vWA) domain containing protein is a
      single gene in rice that is seemingly specific to grasses. GFP-tagged LGD1
      isoforms were predominantly detected in the nucleus, and weakly in the cytoplasm.
      In vitro northwestern analysis showed the RNA-binding activity of the recombinant
      C-terminal LGD1 protein. Our results demonstrated that LGD1 pleiotropically
      regulated rice vegetative growth and development through both the distinct
      spatiotemporal expression patterns of its multiple transcripts and RNA binding
      activity. Hence, the study of LGD1 will strengthen our understanding of the
      molecular basis of the multiple transcripts, and their corresponding polypeptides
      with RNA binding activity, that regulate pleiotropic effects in rice.

PMID- 22409538
TI  - Stability of superparamagnetic iron oxide nanoparticles at different pH values:
      experimental and theoretical analysis.
AB  - The detection of superparamagnetic nanoparticles using NMR logging has the
      potential to provide enhanced contrast in oil reservoir rock formations. The
      stability of the nanoparticles is critical because the NMR relaxivity (R(2) =
      1/T(2)) is dependent on the particle size. Here we use a molecular theory to
      predict and validate experimentally the stability of citric acid-coated/PEGylated
      iron oxide nanoparticles under different pH conditions (pH 5, 7, 9, 11). The
      predicted value for the critical surface coverage required to produce a steric
      barrier of 5k(B)T for PEGylated nanoparticles (MW 2000) was 0.078 nm(-2), which
      is less than the experimental value of 0.143 nm(-2), implying that the
      nanoparticles should be stable at all pH values. Dynamic light scattering (DLS)
      measurements showed that the effective diameter did not increase at pH 7 or 9
      after 30 days but increased at pH 11. The shifts in NMR relaxivity (from R(2)
      data) at 2 MHz agreed well with the changes in hydrodynamic diameter obtained
      from DLS data, indicating that the aggregation behavior of the nanoparticles can
      be easily and quantitatively detected by NMR. The unexpected aggregation at pH 11
      is due to the desorption of the surface coating (citric acid or PEG) from the
      nanoparticle surface not accounted for in the theory. This study shows that the
      stability of the nanoparticles can be predicted by the theory and detected by NMR
      quantitatively, which suggests the nanoparticles to be a possible oil-field
      nanosensor.

PMID- 22409539
TI  - Neonatal outcomes in women with sonographically identified uterine leiomyomata.
AB  - OBJECTIVE: We sought to compare perinatal outcomes between women with and without
      leiomyomata. STUDY DESIGN: This is a retrospective cohort study comparing
      neonatal outcomes in women with and without uterine leiomyomata discovered at
      routine second trimester obstetric ultrasonography, all of whom delivered at a
      single institution. Potential confounders such as maternal age, parity, race,
      ethnicity, medical insurance, previous uterine surgery, fetal presentation,
      length of labor, mode of delivery, presence of placenta previa, placental
      abruption, chorioamnionitis, and epidural use were controlled for using
      multivariable logistic regression. RESULTS: From 1993 to 2003, 15,104 women
      underwent routine second trimester prenatal ultrasonography, with 401 (2.7%)
      women identified with at least one leiomyoma. By univariate and multivariable
      analyses, the presence of leiomyomata was associated with statistically
      significant increased risks for preterm delivery at <34 weeks [adjusted odds
      ratio (AOR) 1.7, 95% confidence interval (CI) 1.1-2.6], <32 weeks (AOR 1.9, 95%
      CI 1.2-3.2), and <28 weeks (AOR 2.0, 95% CI 1.1-3.8). An association with
      increased risk for intrauterine fetal demise (IUFD) was also demonstrated (AOR
      2.7, 95% CI 1.0-6.9). When IUFD was examined before and after 32 weeks'
      gestation, the finding only persisted at earlier gestational ages (<32 weeks: AOR
      4.2, 95% CI 1.2-14.7 vs. >32 weeks: AOR 0.82, 95% CI 0.1-6.2). CONCLUSION:
      Regardless of maternal age, ethnicity, and parity, pregnant women with
      leiomyomata are at increased risk for preterm birth and IUFD. This did not
      translate to lower birth weight outcomes among term patients, suggesting that LBW
      is more likely due to preterm birth than growth restriction. These results may be
      useful for preconception and prenatal counseling of women with leiomyomata.

PMID- 22409540
TI  - gammaH2AX, pChk1, and Wip1 as potential markers of persistent DNA damage derived
      from dibenzo[a,l]pyrene and PAH-containing extracts from contaminated soils.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are formed during incomplete combustion
      of organic material and are ubiquitous environmental contaminants. High levels of
      PAHs are commonly found in soils at industrial sites, thereby constituting a risk
      for humans and the environment. However, this risk is often difficult to estimate
      due to the complexity of the contamination. In the present study, we investigated
      the cellular DNA damage response induced by extracts of PAH-contaminated soils
      collected at various industrial sites in Sweden. The results show that
      interactions of PAHs in the soil extracts caused activation of DNA damage
      signaling consistent with persistent DNA damage. Signaling in HepG2 cells exposed
      to soil PAH extracts corresponding to 1 MUM benzo[a]pyrene was similar to that of
      0.1 MUM dibenzo[a,l]pyrene, a highly carcinogenic PAH known to produce persistent
      DNA damage. The response involved prolonged activation of DNA damage marker
      (H2AX), check point kinase (Chk1), and phosphatases (Wip1). Furthermore, blocking
      DNA damage signaling using specific inhibitors and siRNA showed the important
      role of signaling through Chk1 for the level of DNA damage. We conclude that the
      combination of prolonged Chk1 phosphorylation and induced expression of Wip1
      might serve as potential markers for persistent DNA damage induced by complex
      mixtures of environmental PAHs. Discrepancies between mRNA and protein levels of
      Wip1 in response to soil extracts, in parallel with increased microRNA (miR)-16
      levels, suggest a role of miR-16 in the regulation of DNA damage signaling in
      response to PAHs. Taken together, our data indicate that PAH extracts induce
      irreparable DNA damage and that this is consistent with the prolonged activation
      of DNA damage signaling.

PMID- 22409541
TI  - New technologies, tools and approaches for improving crop breeding.

PMID- 22409543
TI  - Molecular-scale surface chemistry of a common metal nanoparticle capping agent:
      triphenylphosphine on Au(111).
AB  - Phosphine-stabilized Au clusters have been extensively studied and are used in
      various applications due to their unique structural, catalytic, and electronic
      properties. Triphenylphosphine (PPh(3)) is a key stabilizing ligand in the
      synthesis of Au nanoclusters. Despite its intense use in nanoparticle synthesis
      protocols, little is known regarding its surface chemistry, monolayer structure,
      density, and packing arrangement, all of which are important descriptors of
      functionality. Here, in contrast to sparse earlier investigations, we report that
      PPh(3) forms very ordered structures on Au(111). Atomic-scale imaging reveals
      that monolayer formation is accompanied by a partial lifting of the Au(111)
      surface reconstruction and ejection of extra Au atoms in the surface layer.
      Interestingly, these atoms are trapped and stabilized as two-dimensional Au
      nanoislands within the molecular layer. This behavior is in contrast to thiols,
      also common capping agents, which tend to remove Au atoms beyond those extra
      atoms present in the native reconstruction and form vacancy islands on the
      surface. Our data illustrate PPh(3)'s milder reactivity and reveal a new picture
      of its packing structure. These results shed new light on the surface chemistry
      of this important ligand for organic, organometallic, and nanoparticle synthesis.

PMID- 22409542
TI  - Photochromism of a diarylethene having an azulene ring.
AB  - Diarylethene derivatives incorporating an azulene ring at the ethene moiety were
      synthesized. One derivative having thiazole rings showed the expected coloration
      reaction by excitation at 313 nm (to a higher singlet state) but not when excited
      at 635 nm (S(0) to S(1) excitation). The system demonstrates that the cyclization
      reaction can be controlled by selective excitation at different wavelengths of
      the absorption spectrum. On the other hand, another derivative having thiophene
      rings did not show any photochromism. The results clearly show the importance of
      the coplanarity of the system for the photoisomerization.

PMID- 22409545
TI  - HRMS: current usage, future directions and the promise of integration with
      unified data streams suited to post-acquisition mining.

PMID- 22409544
TI  - The emergence of high-resolution MS as the premier analytical tool in the
      pharmaceutical bioanalysis arena.

PMID- 22409547
TI  - Conference Report: High-resolution MS in drug discovery and development: current
      applications and future perspectives.
AB  - The evolving use of high-resolution MS (HRMS) across the pharmaceutical industry
      has seen its integrated application into both quantitative and qualitative
      assays. Through an American Association of Pharmaceutical Scientists (AAPS)/
      American Society for Mass Spectrometry (ASMS) workshop, held at AAPS, key
      scientists from world pharma discussed the feasibility of this new paradigm shift
      through examples and visions for the future, assessing impact on drug discovery
      and drug development, as well as educating users new to HRMS in the field. This
      report details selected talks from the 2-day workshop, with particular emphasis
      on their impact, as well as personal conclusions around certain topics.

PMID- 22409548
TI  - Using high-resolution quadrupole TOF technology in DMPK analyses.
AB  - Recent advances in quadrupole TOF (Q-TOF) MS have some bioanalytical scientists
      referring to a 'paradigm shift' in their field. They are speaking of a potential
      move away from workflows based upon triple-quadrupole MS. Gone would be the
      optimizing of numerous parameters in selected-reaction monitoring (SRM)
      experiments, replaced with more generic workflows provided by Q-TOF instruments
      with high data acquisition rates, excellent mass accuracy (<=5 ppm) and high
      resolving power (>=30,000). Such a move could pay real dividends for high
      throughput workflows, especially in drug metabolism and pharmacokinetics analyses
      where quantitation and qualification studies could actually be merged. But, are
      modern Q-TOF-MS instruments, touted as high-resolution MS, ready for this? If
      not, how close is it? This article will examine these questions by reviewing
      recent advances in Q-TOF technology and some fascinating orthogonal technology
      (such as ion mobility) that modern Q-TOFs employ for even greater analytical
      power.

PMID- 22409549
TI  - Application of LC-high-resolution MS with 'intelligent' data mining tools for
      screening reactive drug metabolites.
AB  - Biotransformation of chemically stable compounds to reactive metabolites that can
      bind covalently to macromolecules (such as proteins and DNA) is considered an
      undesirable property of drug candidates. Due to the possible link, which has not
      yet been conclusively demonstrated, between reactive metabolites and adverse drug
      reactions, screening for metabolic activation of lead compounds through in vitro
      chemical trapping experiments has become an integral part of the drug discovery
      process in many laboratories. In this review, we provide an overview of the
      recent advances in the application of high-resolution MS. These advances
      facilitated the development of accurate-mass-based data mining tools for high
      throughput screening of reactive drug metabolites in drug discovery.

PMID- 22409550
TI  - Integrated quantitative and qualitative workflow for in vivo bioanalytical
      support in drug discovery using hybrid Q-TOF-MS.
AB  - BACKGROUND: UHPLC coupled with orthogonal acceleration hybrid quadrupole-TOF (Q
      TOF)-MS is an emerging technique offering new strategies for the efficient
      screening of new chemical entities and related molecules at the early discovery
      stage within the pharmaceutical industry. In the first part of this article, we
      examine the main instrumental parameters that are critical for the integration of
      UHPLC-Q-TOF technology to existing bioanalytical workflows, in order to provide
      simultaneous quantitative and qualitative bioanalysis of samples generated
      following in vivo studies. MATERIAL & METHODS: Three modern Q-TOF mass
      spectrometers, including Bruker maXisTM, Agilent 6540 and Sciex TripleTOFTM 5600,
      all interfaced with UHPLC systems, are evaluated in the second part of the
      article. The scope of this work is to demonstrate the potential of Q-TOF for the
      analysis of typical small molecules, therapeutic peptides (molecular weight <6000
      Da), and enzymatically (i.e., trypsin, chymotrypsin and pepsin) cleaved peptides
      from larger proteins. RESULTS & DISCUSSION: This work focuses mainly on full-scan
      TOF data obtained under ESI conditions, the major mode of TOF operation in
      discovery bioanalytical research, where the compounds are selected based on their
      pharmacokinetic/pharmacodynamic behaviors using animal models prior to selecting
      a few desirable candidates for further development. Finally, important emerging
      TOF technologies that could potentially benefit bioanalytical research in the
      semi-quantification of metabolites without synthesized standards are discussed.
      Particularly, the utility of captive spray ionization coupled with TripleTOF 5600
      was evaluated for improving sensitivity and providing normalized MS response for
      drugs and their metabolites. The workflow proposed compromises neither the
      efficiency, nor the quality of pharmacokinetic data in support of early drug
      discovery programs.

PMID- 22409551
TI  - Large molecule bioanalysis using Q-TOF without predigestion and its data
      processing challenges.
AB  - BACKGROUND: Recent developments in LC-MS have turned it into a viable and valid
      alternative to ligand-binding assays. Large molecule bioanalysis by LC-MS is
      generally performed by tryptic digestion, purification and detection of one or
      more small signature peptides. High-resolution MS instruments offer
      quantification of intact small proteins or peptides and are able to increase the
      selectivity, while maintaining sensitivity. RESULTS: Unlike multiple reaction
      monitoring assays, several factors affecting data processing were presented and
      the optimal parameters to consider during quantification method building were
      also demonstrated. MUC5AC-13 (MW 1709.8 Da), human hepcidin/LEAP-1 (MW 2797.4
      Da), porcine calcitonin (MW 3604 Da) and chicken lysozyme (MW 14.3 kDa) were
      selected as model compounds and the possibility of intact peptide and small
      protein quantification, without tryptic digestion, was demonstrated. CONCLUSION:
      Selectivity and sensitivity were improved using different scan modes, such as TOF
      MS and TOF-MS/MS.

PMID- 22409552
TI  - Automated and unbiased analysis of LC-MS metabolomic data.
AB  - BACKGROUND: LC-MS metabolomics provides a unique approach for evaluation of
      perturbations in biochemical pathways. LC-MS is a key technology for measuring
      endogenous metabolites and, while it has the impressive ability to acquire
      colossal volumes of data, the overall success of a study depends on the ability
      to translate the acquired analytical information into biological knowledge. Thus,
      a significant research effort has been dedicated to the development of
      informatics tools capable of automatically translating the complexity of acquired
      LC-MS datasets into meaningful biochemical sample descriptions. MATERIALS &
      METHODS: This article discusses our methodology for automated analysis of high
      resolution accurate mass LC-MS data applied to a case study of evaluation of the
      effects of fasting in male rats. Blood serum samples from male rats were analyzed
      using an exactive mass spectrometer interfaced with an Accela UHPLC. RESULTS: An
      obtained list of annotated endogenous metabolites through matching of the
      detected components with corresponding profiles of synthetic standards served as
      a basis for statistical evaluation of observed physiological changes. CONCLUSION:
      The observed changes in certain endogenous metabolites prove that fasting could
      be a significant variable in toxicological studies since the fasting status of a
      particular animal may exacerbate or obscure drug-induced metabolic effects.

PMID- 22409553
TI  - Comparison of unit resolution SRM and TOF-MS at 12,000 mass resolution for
      quantitative bioanalysis of 11 steroids from human plasma.
AB  - BACKGROUND: The use of high-resolution MS systems for quantitative bioanalysis is
      a growing field, even though a clear majority of bioanalytical methods are still
      based on MS/MS with triple quadrupole (QqQ) instrumentation. The recent advances
      in TOF-MS technology have provided increased linear range and a high selectivity
      of detection by increased mass resolution and mass accuracy, making these
      instruments attractive for quantitative analysis due to lack of a need for
      compound-specific detection reaction optimization and their capability to collect
      data for a high number of compounds by sensitive wide mass range data
      acquisition. MATERIALS & METHODS: Here, 11 steroids spiked to human plasma were
      analyzed by LC-MS using both a QqQ MS system and a TOF instrument operating at
      12,000 mass resolution. Sample preparation was performed by hybrid SPE
      technology. RESULTS: The LOD were 0.5-5 and 0.5-20 ng/ml in plasma for all
      analytes with QqQ and TOF-MS detection, respectively. CONCLUSION: Although the
      results show wider linear range and slightly better sensitivity for most of the
      compounds with QqQ in comparison to TOF, acceptable performance was obtained for
      most of the compounds within the range of LOD to 2000 ng/ml (in plasma), this was
      also the case with LC-TOF-MS analysis. The main problem in TOF-MS analysis at
      12,000 mass resolution from plasma was selectivity rather than sensitivity or
      linear range.

PMID- 22409554
TI  - Comparison of triple quadrupole and high-resolution TOF-MS for quantification of
      peptides.
AB  - BACKGROUND: With an increased interest in peptides and proteins as potential new
      drug candidates, new approaches for sensitive and selective quantitative analysis
      are required. LC-MS/MS analysis provides a good alternative to immunoassays with
      reduced method development times and increased specificity. RESULTS: We have
      evaluated two state-of-the-art triple quadrupole and high-resolution TOF mass
      spectrometers with respect to their performance for quantification of six
      peptides (glufibrinopeptide B, somatostatin, enfuvirtide, TRI1144, C34 and
      exenatide). The peptides were spiked into protein-precipitated plasma
      supernatant. Triple quadrupole quantification was performed in SRM mode, and in
      high-resolution, MS narrow-width extracted chromatograms were generated for
      quantification. Specificity, accuracy, reproducibility and robustness were found
      to be comparable between the two instruments. The triple quadrupole instrument is
      still the most sensitive instrument for quantification of peptides with a median
      factor of about four-times higher sensitivity (based on LLOQ evaluation).
      CONCLUSION: Based on sensitivity, the newest generation triple quadrupole MS
      systems are still the preferred technology for quantification of peptides. Since
      the sensitivity difference between triple quadrupole instruments and the new
      generation high-resolution TOF-MS instruments is minor, the latter offer a useful
      alternative whenever additional selectivity is preferred or the use of a generic
      approach not requiring method optimization is advantageous.

PMID- 22409555
TI  - Cassette incubation followed by bioanalysis using high-resolution MS for in vitro
      ADME screening assays.
AB  - BACKGROUND: High-resolution MS (HRMS) has recently received a considerable
      interest in quantitative bioanalysis using full-scan acquisition mode. The
      benefits include complete elimination of compound-specific MS method development,
      and simultaneous collection of mass spectral data on both targeted and non
      targeted components. One additional advantage that has not been widely discussed
      is its suitability for simultaneous quantitation of, theoretically, an unlimited
      number of compounds, which is not possible with selected reaction monitoring
      (SRM) on a triple quadrupole mass spectrometer. MATERIALS & METHODS: We took
      advantage of this unique bioanalytical capability of HRMS and developed a novel
      in vitro ADME workflow of cassette incubation of as many as 32 compounds,
      followed by quantitative bioanalysis using full-scan acquisition on an Orbitrap
      HRMS. The workflow was evaluated for a serum protein-binding assay and a parallel
      artificial membrane permeability (PAMPA) assay. RESULTS: The bioanalytical assay
      displayed acceptable sensitivity, selectivity and linearity for all compounds in
      the cassettes, and the biological results obtained using this approach were
      similar to those from discrete incubation and analysis, demonstrating the
      feasibility of the workflow. Additional benefits of this platform include a
      saving of analysis time due to the reduced sample numbers from the cassette
      approach, as well as cost saving due to the reduction in the required assay
      reagents. CONCLUSION: Cassette incubation with bioanalysis using HRMS is a
      feasible approach for high-throughput in vitro ADME assays evaluated in this
      study.

PMID- 22409556
TI  - Identifying metabolite ions of peptide drugs in the presence of an in vivo matrix
      background.
AB  - BACKGROUND: Peptides represent a growing class of potential drugs. Information on
      metabolic clearance can be valuable for peptide drug development but different
      challenges are encountered with the identification of peptide metabolites in
      comparison to the process used for small-molecule therapeutics. RESULTS:
      Enfuvirtide was selected as a test compound and dosed intravenously at 2 mg/kg to
      rats. Plasma samples were collected and analyzed on two different quadrupole-TOF
      instruments in positive and negative ion modes. Different post-acquisition
      processing tools were evaluated to identify the metabolites of a peptide drug in
      the presence of an in vivo matrix. Charge state filtering and ion mobility
      extraction were applied to reduce the matrix background and combined with more
      comprehensive software tools generally used for large molecule analyses as well
      as tools designed for small-molecule metabolite identification work. CONCLUSION:
      Both ion mobility spectrometry and charge state filtration proved to be
      successful in extracting peptide ions and significantly reducing background
      signals. Both small- and large-molecule software tools contain specific
      capabilities that could be usefully combined in a single package for peptide
      metabolite identification.

PMID- 22409557
TI  - Comparison of the quantification of a therapeutic protein using nominal and
      accurate mass MS/MS.
AB  - BACKGROUND: The quantification of proteins and peptides in in vivo samples is a
      critical part of supporting the drug development process for biotherapeutics. LC
      MS/MS using tandem quadrupole mass spectrometers is well established as the
      technology of choice for the quantification of small-molecule drugs and their
      metabolites in biological fluid. The application of accurate mass MS for
      quantification in a DMPK environment has attracted considerable interest in
      recent years. MATERIALS & METHODS: In this article we describe and compare the
      application of LC-high-resolution MS and LC-selected reaction monitoring (SRM)
      for the quantification of a therapeutics proteins. RESULTS: The accurate mass
      instrumentation showed acceptable linearity and sensitivity to quantify the
      protein therapeutic to the level of 10 ng/ml. The accurate mass instrument was
      operated in accurate mass SRM using high resolution (SRM-HR), the assay was
      demonstrated to be linear over three orders of magnitude. By narrowing the mass
      window from 100 mDa to 40 mDa and then to 20 mDa the assay specificity was
      significantly improved, hence increasing the S/N and improving the assay
      sensitivity. CONCLUSION: The high-resolution instrument was demonstrated to be
      reproducible over the course of the assay. The accurate mass method sensitivity
      was determined to be within one order of magnitude of that obtained with a tandem
      quadrupole MS/MS assay.

PMID- 22409558
TI  - Epidemiology of ocular toxoplasmosis.
AB  - Retinal infection with Toxoplasma gondii is the most important cause of posterior
      uveitis, whereby prevalence and incidence of ocular symptoms after infection
      depend on socio-economic factors and the circulating parasite genotypes. Ocular
      toxoplasmosis is more common in South America, Central America, and the Caribbean
      and parts of tropical Africa as compared to Europe and Northern America, and is
      quite rare in China. Ocular disease in South America is more severe than in other
      continents due to the presence of extremely virulent genotypes of the parasite.
      Drinking untreated water is considered the major source of Toxoplasma infection
      in developing countries, whereas in the Western world the consumption of raw or
      undercooked meat (products) is the most important cause. Since acquired infection
      with T. gondii is currently a more important cause of ocular toxoplasmosis
      compared to congenital infection, prevention should be directed not only toward
      pregnant women but toward the general population.

PMID- 22409559
TI  - Central serous chorioretinopathy, corticosteroids, and uveitis.
AB  - Any patient with a diagnosis of central serous chorioretinopathy (CSCR) should be
      questioned to determine any recent corticosteroid use, as the poor visual outcome
      may be due to unrecognized corticosteroid use. Atypical forms of CSCR may be
      misdiagnosed as an inflammatory serous retinal detachment, mainly Vogt-Koyanagi
      Harada disease. CSCR that develops in association with preexisting uveitis could
      be a challenging diagnosis as it might be misinterpreted as a worsening of the
      primary inflammatory condition. Failure to differentiate CSCR from retinal or
      choroidal inflammatory diseases may result in inappropriate use of
      corticosteroids, leading to exacerbation of the condition and permanent visual
      loss. Discontinuation of corticosteroids should be the first step in the
      treatment of CSCR associated with corticosteroid therapy, and the use of
      immunosuppressive or immunomodulatory drugs may be required to control systemic
      or ocular inflammatory disease. The prognosis is usually favorable, but
      persistent visual loss may occur.

PMID- 22409560
TI  - Interferon alpha 2b in the treatment of uveitic cystoid macular edema.
AB  - PURPOSE: To determine the efficacy of interferon alpha 2b in the treatment of
      refractory, uveitic cystoid macular edema (CME). METHODS: Retrospective chart
      review of 4 patients attending the uveitis clinic at the Casey Eye Institute,
      Oregon Health & Science University. RESULTS: All 4 patients had uveitis and
      refractory CME, resistant to a variety of immunosuppressants. All patients,
      except one with severe scleral thinning, had tried and failed therapy with
      locally injected corticosteroids. Treatment with systemic interferon alpha 2b
      produced dramatic improvement in CME (central macular thickness: 563 to 267 um, p
      = .002) and visual acuity (logMAR: +0.81 to +0.45, p = .0004) in all 4 cases. All
      patients have been able to reduce the interferon dosage, but none has
      discontinued it completely. All patients had some mild adverse response that did
      not necessitate stopping therapy. CONCLUSIONS: Interferon alpha 2b is an
      effective option to treat refractory CME secondary to uveitis.

PMID- 22409561
TI  - High-dose intravenous corticosteroids for ocular inflammatory diseases.
AB  - PURPOSE: To evaluate the effectiveness and risk of complications of high-dose
      intravenous pulsed corticosteroids for noninfectious ocular inflammatory
      diseases. METHODS: Retrospective cohort study in which 104 eyes of 70 patients
      who received high-dose intravenous corticosteroids for treatment of active ocular
      inflammation were identified from five centers. The main outcome measures were
      control of inflammation and occurrence of ocular or systemic complications within
      1 month after treatment. RESULTS: Within <=1 month of starting treatment, 57% of
      eyes achieved complete control of inflammation (95% confidence interval (CI): 33
      83%), improving to 82% when near-complete control was included (95% CI: 61-96%).
      Most eyes (85%; 95% CI: 70-95%) gained clinically significant improvement in
      anterior chamber inflammation. One patient developed a colon perforation during
      treatment. No other major complications were recorded. CONCLUSIONS: Treatment of
      ocular inflammation with high-dose intravenous corticosteroids resulted in
      substantial clinical improvement for most cases within 1 month. Complications of
      therapy were infrequent.

PMID- 22409562
TI  - Ocular involvement in hospitalized patients with candidemia: analysis at a Boston
      tertiary care center.
AB  - PURPOSE: To study the prevalence, microbial profile, and risk factors for ocular
      involvement in patients with candidemia. METHODS: The records of all inpatient
      consultations requested at the Brigham and Women's Hospital from October 2009 to
      June 2011 to evaluate for ocular involvement in patients with candidemia were
      retrospectively reviewed. RESULTS: Forty-nine consults were requested to rule out
      ocular involvement in patients with candidemia. The mean patient age was 55
      years. In decreasing frequency, the organisms isolated were Candida albicans
      (42%), Candida parapsilosis (23%), Candida glabrata (17%), Candida tropicalis
      (8%), Candida dublinensis (5%), Candida krusei (3%), and Candida lusitaniae (3%).
      All patients were on antifungal treatment at the time of their initial
      ophthalmologic examination. One patient had evidence of chorioretinitis, and 3
      patients had nonspecific fundus findings. Common risk factors included presence
      of an intravenous catheter, malignancy, and abdominal surgery. CONCLUSIONS:
      Ocular involvement is rare among patients with systemic Candida infection.

PMID- 22409564
TI  - Mycophenolate mofetil in the treatment of chronic non-infectious, non-necrotizing
      scleritis.
AB  - PURPOSE: To determine the effectiveness and corticosteroid (CS) sparing
      capabilities of mycophenolate mofetil (MMF) in the treatment of chronic non
      infectious, non-necrotizing scleritis. METHODS: A retrospective chart review of
      patients treated for scleritis at the Institute of Ophthalmology and Visual
      Science at New Jersey Medical School was performed. Only those patients taking
      MMF for greater than or equal to six consecutive months were included. Main
      outcome measures were rate of inflammation control, CS, and MMF discontinuation,
      as well as visual acuity and side effects. RESULTS: Twenty-two patients (32 eyes)
      were included in the study. Mean +/- SD age was 53.5 +/- 13.3 years. Twenty (91%)
      patients had previously failed some form of immunomodulatory therapy. After 6,
      12, 18, and 24 months of consecutive MMF treatment, 91-100% of patients achieved
      inflammation control. Mean time to resolution of inflammation was 2.8 months,
      while mean duration of inflammation control was 14.8 months. CS sparing was
      achieved in 100% of patients at each time point, with mean starting CS dose
      decreased by 91% at final visit. Vision was stable or improved in 24 (75%) eyes.
      Fourteen (64%) patients reported side effects including leucopenia (n = 7),
      gastrointestinal upset (n = 4), abnormal liver function tests (n = 3), and
      abnormal renal function tests (n = 2). None required hospitalization or medical
      treatment. Four (18%) patients discontinued MMF due to side effects (n = 3) and
      treatment ineffectiveness (n = 1). CONCLUSION: MMF is an effective and well
      tolerated therapy that can successfully reduce inflammation and decrease CS use
      in the treatment of chronic non-infectious, non-necrotizing scleritis.

PMID- 22409565
TI  - Demographic, clinical, and ocular features in patients with late-onset Behcet
      disease.
AB  - PURPOSE: To evaluate demographic, clinical, and ocular features of patients with
      late-onset Behcet disease (BD). METHODS: The study included 26 patients with late
      onset BD. Onset of their first symptoms was before age 40. They fulfilled the
      diagnostic criteria after age 40. Patients were divided into 2 groups: group 1
      had uveitis and group 2 had no uveitis. Clinical and demographic features of the
      groups were compared. Ocular manifestations in group 1 were also evaluated.
      RESULTS: Fourteen patients (53.8%) had uveitis and 12 patients (46.2%) had no
      ocular involvement. The incidence of genital ulcer was higher in group 1. Twelve
      patients (18 eyes) had anterior uveitis and 2 patients (4 eyes) had panuveitis.
      The incidence of anterior uveitis was higher in females. The incidence of
      panuveitis was higher in males. CONCLUSIONS: As compared to potentially
      devastating posterior uveitis, anterior uveitis is more often encountered in
      patients with late-onset BD. Hence, with respect to ocular involvement, the
      prognosis is better.

PMID- 22409566
TI  - The efficacy of topical interferon alpha 2b treatment in refractory vernal
      keratoconjunctivitis.
AB  - PURPOSE: This study aimed to investigate the efficacy and safety of a 2-month
      topical interferon alpha 2b treatment in patients with refractory vernal
      keratoconjunctivitis. METHODS: Twelve (10 male, 2 female) patients with
      refractory vernal keratoconjunctivitis received topical treatment with one
      million IU/mL interferon alpha 2b 4 times a day for 2 months. Symptom and
      ophthalmological examination scores were assessed at baseline and during follow
      up. RESULTS: No significant complications or side effects associated with the use
      of topical interferon alpha 2b were observed. Symptom scores for itching,
      tearing, photophobia, and total symptom score, and objective scores for corneal
      lesion, hyperemia, chemosis, papillary hypertrophy, secretion, and total
      examination score significantly improved during the 2-month treatment.
      Improvements were maintained after discontinuation of the treatment for most
      parameters. CONCLUSIONS: Topical interferon alpha 2b treatment seems to offer a
      safe and effective alternative for the treatment of refractory vernal
      keratoconjunctivitis for a brief period.

PMID- 22409567
TI  - Ocular toxoplasmosis: clinical characteristics in pediatric patients.
AB  - PURPOSE: To describe the clinical features of Ocular Toxoplasmosis in pediatric
      patients. METHODS: A retrospective, non-comparative series of cases was studied.
      We reviewed the clinical records of patients 16 year old or younger diagnosed
      with Ocular Toxoplasmosis. RESULTS: Forty patients (56 eyes) were included. The
      mean age was 9.5 yrs old. Twenty were female. Unilateral involvement was noticed
      in 60% of patients. The most common symptoms were strabismus (32.1%) and reduced
      VA in (23.2%). An inactive retinal scar was observed in most cases (71.4%).
      Panuveitis was found in 8 eyes (14.2%), and posterior uveitis in 7 eyes of 7
      patients (12.5%); one eye presented neuroretinitis. The most frequent location of
      retinochoroidal lesions was the posterior pole (72.7%). CONCLUSIONS: In children,
      ocular toxoplasmosis is most commonly diagnosed during the inactive stage. When
      inflammation is present, it can be severe and frequently associated with other
      complications such vasculitis and papillitis.

PMID- 22409568
TI  - Ophthalmomyiasis externa caused by Muscae fly larva in deserts of the Thar.

PMID- 22409569
TI  - Author response to "Intraocular cysticercosis" by Somsri Wiwanitkit and Viroj
      Wiwanitkit.

PMID- 22409573
TI  - Benzothiazinones: a novel class of adenosine receptor antagonists structurally
      unrelated to xanthine and adenine derivatives.
AB  - 2-(Acyl)amino-4H-3,1-benzothiazin-4-ones and related thienothiazinones were
      identified as structurally novel antagonists at adenosine receptors (ARs). 6
      Methyl-2-benzoylamino-4H-3,1-benzothiazin-4-one (10d) was found to be a balanced
      AR antagonist with affinity for all human (h) subtypes (K(i) hA(1) 65.6 nM;
      hA(2A) 120 nM; hA(2B) 360 nM; hA(3) 30.4 nM), while in rat (r), 10d was a highly
      potent A(1)-selective antagonist (rA(1) 7.7 nM; rA(2A) 546 nM; rA(2B) 679 nM,
      rA(3) >10000 nM). 2-(4-Methylbenzoylamino)-4H-3,1-benzothiazin-4-one (10g) was
      found to be a potent antagonist at human A(2A) (68.8 nM) and A(3) ARs (23.0 nM)
      with high selectivity versus the other human AR subtypes. In contrast to A(1) and
      A(3) ARs, A(2A) and A(2B) ARs tolerated bulky 2-acyl substituents. tert-Butyl (4
      oxo-4H-3,1-benzothiazin-2-ylcarbamoyl)benzylcarbamate (15g, K(i) hA(2B) 186 nM;
      hA(2A) 603 nM) and 4-(4-benzylpiperazine-1-carbonyl)-N-(4-oxo-4H-3,1-benzothiazin
      2-yl)benzamide (15k, hA(2A) 69.5 nM; hA(2B) 178 nM) were highly selective versus
      the other AR subtypes. 2-Acylamino-3,1-benzothiazin-4-ones represent novel
      scaffolds suitable for the development of potent and selective AR antagonists for
      each of the four receptor subtypes.

PMID- 22409572
TI  - Beyond conventional antibiotics for the future treatment of methicillin-resistant
      Staphylococcus aureus infections: two novel alternatives.
AB  - The majority of antibiotics currently used to treat methicillin-resistant
      Staphylococus aureus (MRSA) infections target bacterial cell wall synthesis or
      protein synthesis. Only daptomycin has a novel mode of action. Reliance on
      limited targets for MRSA chemotherapy, has contributed to antimicrobial
      resistance. Two alternative approaches to the treatment of S. aureus infection,
      particularly those caused by MRSA, that have alternative mechanisms of action and
      that address the challenge of antimicrobial resistance are cationic host defence
      peptides and agents that target S. aureus virulence. Cationic host defence
      peptides have multiple mechanisms of action and are less likely than conventional
      agents to select resistant mutants. They are amenable to modifications that
      improve their stability, effectiveness and selectivity. Some cationic defence
      peptides such as bactenecin, mucroporin and imcroporin have potent in vitro
      bactericidal activity against MRSA. Antipathogenic agents also have potential to
      limit the pathogenesis of S aureus. These are generally small molecules that
      inhibit virulence targets in S. aureus without killing the bacterium and
      therefore have limited capacity to promote resistance development. Potential
      antipathogenic targets include the sortase enzyme system, the accessory gene
      regulator (agr) and the carotenoid biosynthetic pathway. Inhibitors of these
      targets have been identified and these may have potential for further
      development.

PMID- 22409574
TI  - Intraoperative lactate levels and postoperative complications of pediatric
      cardiac surgery.
AB  - OBJECTIVES: Correlate arterial lactate levels during the intraoperative period of
      children undergoing cardiac surgery and the occurrence of complications in the
      postoperative period. AIM: Arterial lactate levels can indicate hypoperfusion
      states, serving as prognostic markers of morbidity and mortality in this
      population. BACKGROUND: Anesthesia for cardiac pediatric surgery is frequently
      performed on patients with serious abnormal physiological conditions. During the
      intraoperative period, there are significant variations of blood volume, body
      temperature, plasma composition, and tissue blood flow, as well as the activation
      of inflammation, with important pathophysiological consequences.
      METHODS/MATERIALS: Chart data relating to the procedures and perioperative
      conditions of the patients were collected on a standardized form. Comparisons of
      arterial lactate values at the end of the intraoperative period of the patients
      that presented, or not, with postoperative complications and frequencies related
      to perioperative conditions were established by odds ratio and nonparametric
      univariate analysis. RESULTS: After surgeries without cardiopulmonary bypass
      (CPB), higher levels of arterial lactate upon ICU admission were observed in
      patients who had renal complications (2.96 vs 1.31 mm) and those who died (2.93
      vs 1.40 mm). For surgeries with CPB, the same association was observed for
      cardiovascular (2.90 mm * 2.06 mm), renal (3.34 vs 2.33 mm), respiratory (2.98 vs
      2.12 mm) and hematological complications (2.99 vs 1.95 mm), and death (3.38 vs
      2.40 mm). CONCLUSION: Elevated intraoperative arterial lactate levels are
      associated with a higher morbidity and mortality in low- and medium-risk
      procedures, with or without CPB, in pediatric cardiac surgery.

PMID- 22409563
TI  - Hypotony in patients with uveitis: The Multicenter Uveitis Steroid Treatment
      (MUST) Trial.
AB  - PURPOSE: To assess the prevalence of hypotony in patients with severe forms of
      uveitis. METHODS: The Multicenter Uveitis Steroid Treatment (MUST) Trial, a
      randomized study, enrolled 255 patients. Patients with hypotony at the baseline
      visit were identified. RESULTS: Twenty (8.3%) of 240 patients with sufficient
      data had hypotony. Hypotony was more common in patients with uveitis >=5 years
      duration (odds ratio [OR] = 5.0; p < .01), and in eyes with a history of ocular
      surgery (vitrectomy vs. none, OR = 3.1; p = .03). Hypotony was less in patients
      with older age of uveitis onset (>51 years vs. <51 years, OR = 0.1; p = .02), in
      Caucasian patients (OR = 0.1; p < .01) compared to African American patients.
      Hypotonous eyes were more likely to have visual impairment (OR = 22.9; p < .01).
      CONCLUSIONS: Hypotony is an important complication of uveitis and more commonly
      affects African-American patients, those with uveitis onset at a younger age, and
      those with longer disease duration. It is associated with visual impairment.

PMID- 22409575
TI  - Alien plant species with a wider global distribution are better able to
      capitalize on increased resource availability.
AB  - * A high ability of alien plant species to capitalize on increases in resource
      availability has been suggested as an explanation for being globally successful.
      Here, we tested this hypothesis meta-analytically using existing data from
      experiments manipulating plant resources (light, water and nutrients). * From
      these studies we extracted the response to resource increase of biomass, as an
      indicator of plant performance, and the responses of two traits related to
      resource capture: root : shoot ratio and specific leaf area (SLA). For 211
      species recorded in the Global Compendium of Weeds, we assessed the relationship
      between effect sizes from such studies and the number of global regions where a
      species was established. * We found that globally widespread species exhibited
      greater biomass responses to increases in resources overall, compared to less
      widespread species. Root : shoot ratio and SLA responses to increased resource
      availability were not related to species global distribution. * In general,
      globally widespread alien plant species were better able to capitalize on
      increased availability of resources, through achieving increased growth and
      biomass accumulation, while greater plasticity of key resource-capture traits per
      se did not appear to be related to greater success.

PMID- 22409578
TI  - VGKC-complex antibody mediated encephalitis presenting with psychiatric features
      and neuroleptic malignant syndrome - further expanding the phenotype.

PMID- 22409577
TI  - Competitive [2,3]- and [1,2]-oxonium ylide rearrangements. Concerted or stepwise?
AB  - The axial-equatorial conformational isomer distribution of the reactant
      diazoacetoacetate or its metal carbene intermediate is reflected in Rh(II)
      catalyzed oxonium ylide forming reactions of 3-(trans-2
      arylvinyl)tetrahydropyranone-5-diazoacetoacetates that afford diastereoisomeric
      products for both the symmetry-allowed [2,3]- and the formally symmetry-forbidden
      [1,2]-oxonium ylide rearrangements.

PMID- 22409580
TI  - Quantification of the surface diffusion of tripodal binding motifs on graphene
      using scanning electrochemical microscopy.
AB  - The surface diffusion of a cobalt bis-terpyridine, Co(tpy)(2)-containing tripodal
      compound (1.2PF(6)), designed to noncovalently adsorb to graphene through three
      pyrene moieties, has been studied by scanning electrochemical microscopy (SECM)
      on single-layer graphene (SLG). An initial boundary approach was designed in
      which picoliter droplets (radii ~15-50 MUm) of the tripodal compound were
      deposited on an SLG electrode, yielding microspots in which a monolayer of the
      tripodal molecules is initially confined. The time evolution of the
      electrochemical activity of these spots was detected at the aqueous phosphate
      buffer/SLG interface by SECM, in both generation/collection (G/C) and feedback
      modes. The tripodal compound microspots exhibit differential reactivity with
      respect to the underlying graphene substrate in two different electrochemical
      processes. For example, during the oxygen reduction reaction, adsorbed 1.2PF(6)
      tripodal molecules generate more H(2)O(2) than the bare graphene surface. This
      product was detected with spatial and temporal resolution using the SECM tip. The
      tripodal compound also mediates the oxidation of a Fe(II) species, generated at
      the SECM tip, under conditions in which SLG shows slow interfacial charge
      transfer. In each case, SECM images, obtained at increasing times, show a gradual
      decrease in the electrochemical response due to radial diffusion of the adsorbed
      molecules outward from the microspots onto the unfunctionalized areas of the SLG
      surface. This response was fit to a simple surface diffusion model, which yielded
      excellent agreement between the two experiments for the effective diffusion
      coefficients: D(eff) = 1.6 (+/-0.9) * 10(-9) cm(2)/s and D(eff) = 1.5 (+/-0.6) *
      10(-9) cm(2)/s for G/C and feedback modes, respectively. Control experiments
      ruled out alternative explanations for the observed behavior, such as
      deactivation of the Co(II/III) species or of the SLG, and verified that the
      molecules do not diffuse when confined to obstructed areas. The noncovalent
      nature of the surface functionalization, together with the surface reactivity and
      mobility of these molecules, provides a means to couple the superior electronic
      properties of graphene to compounds with enhanced electrochemical performance, a
      key step toward developing dynamic electrode surfaces for sensing,
      electrocatalysis, and electronic applications.

PMID- 22409581
TI  - Dodecanuclear [Cu(II)6Gd(III)6] nanoclusters as magnetic refrigerants.
AB  - A novel dodecanuclear complex, [{(HL)(L)(DMF)Cu(II)Gd(III)(DMF)(H(2)O)}(6)].6DMF
      (1; DMF = N,N-dimethylformamide), has been obtained using the ligand resulting
      from the condensation of 3-formylsalicylic acid with hydroxylamine (H(3)L). The
      exchange interaction between the phenoxo-bridged Cu(II) and Gd(III) ions is weak
      ferromagnetic (J = +1.01 cm(-1)). The combination of a high-spin ground state
      with small anisotropy leads to a significant magnetocaloric effect [-DeltaS(m)(0
      7 T) = 23.5 J K g(-1) K(-1) at ~2 K].

PMID- 22409582
TI  - Education for impact.

PMID- 22409583
TI  - Peer review under the spotlight in the UK.

PMID- 22409585
TI  - Patterns of care in the management of seminoma stage I: results from a European
      survey.
AB  - Study Type - Therapy (practise pattern survey). Level of Evidence 3b. What's
      known on the subject? and What does the study add? The uncertainties about
      differences in relapse and rates of other late events such as second malignancy
      and cardiovascular events for the three post-orchidectomy strategies in seminoma
      stage I patients has led to debates about whether the three strategies are
      equally effective and safe. The differences in interpretation of the data as well
      as the debates are likely to result in differences in treatment after
      orchidectomy in seminoma stage I patient management. Current care patterns after
      orchidectomy are, however, unknown. We assessed patterns of care for seminoma
      stage I patients after orchidectomy by distributing a survey among doctors
      treating such patients across Europe. The 969 respondents showed large
      differences in care strategies between specialties and countries that indicate
      the need for research into long-term relapse rates and long-term adverse effects
      to standardize and optimize care for seminoma stage I patients. OBJECTIVE: * To
      assess precise patterns of care after orchidectomy in Europe for stage I seminoma
      patients, we aimed to perform a survey among doctors in the various European
      countries. PATIENTS AND METHODS: * We distributed a survey in 2009 and 2010 among
      American Society of Clinical Oncology and European Association of Urology
      members. RESULTS: * In total, 969 questionnaires were included in the analysis.
      More than half of the 969 physicians (58%) currently offer only one post-surgical
      treatment: 18% only surveillance, 19% only radiotherapy and 21% only
      chemotherapy. Thirteen percent of the 969 physicians currently offer all three
      strategies, 25% offer surveillance and adjuvant radiotherapy or chemotherapy, and
      5% offer either adjuvant radiotherapy or chemotherapy without surveillance. * We
      found large differences in care patterns between specialties and countries. Even
      within countries, care after orchidectomy was not standardized. * Before 2005,
      73% of the physicians offered only one treatment and of those 51% gave adjuvant
      radiotherapy. CONCLUSIONS: * Large differences in pattern of care after
      orchidectomy for stage I seminoma patients exist between specialties and
      countries within Europe. * More information on long-term relapse rates and long
      term adverse effects of the three strategies is needed to standardize and
      optimize care after orchidectomy.

PMID- 22409576
TI  - De novo assembly and characterisation of the transcriptome during seed
      development, and generation of genic-SSR markers in peanut (Arachis hypogaea L.).
AB  - BACKGROUND: The peanut (Arachis hypogaea L.) is an important oilseed crop in
      tropical and subtropical regions of the world. However, little about the
      molecular biology of the peanut is currently known. Recently, next-generation
      sequencing technology, termed RNA-seq, has provided a powerful approach for
      analysing the transcriptome, and for shedding light on the molecular biology of
      peanut. RESULTS: In this study, we employed RNA-seq to analyse the transcriptomes
      of the immature seeds of three different peanut varieties with different oil
      contents. A total of 26.1-27.2 million paired-end reads with lengths of 100 bp
      were generated from the three varieties and 59,077 unigenes were assembled with
      N50 of 823 bp. Based on sequence similarity search with known proteins, a total
      of 40,100 genes were identified. Among these unigenes, only 8,252 unigenes were
      annotated with 42 gene ontology (GO) functional categories. And 18,028 unigenes
      mapped to 125 pathways by searching against the Kyoto Encyclopedia of Genes and
      Genomes pathway database (KEGG). In addition, 3,919 microsatellite markers were
      developed in the unigene library, and 160 PCR primers of SSR loci were used for
      validation of the amplification and the polymorphism. CONCLUSION: We completed a
      successful global analysis of the peanut transcriptome using RNA-seq, a large
      number of unigenes were assembled, and almost four thousand SSR primers were
      developed. These data will facilitate gene discovery and functional genomic
      studies of the peanut plant. In addition, this study provides insight into the
      complex transcriptome of the peanut and established a biotechnological platform
      for future research.

PMID- 22409586
TI  - Parecoxib mitigates spatial memory impairment induced by sevoflurane anesthesia
      in aged rats.
AB  - BACKGROUND: Inflammation in brain plays a critical role in the pathogenesis of
      cognitive impairment. Anti-inflammatory therapy may thus constitute a novel
      approach for associated cognitive dysfunction. The present study investigated the
      effects of parecoxib in the prevention of cognitive impairments induced by
      sevoflurane in aged rats. METHODS: Sixty-six aged rats were divided randomly into
      three groups: control group (n = 22, sham anesthesia), sevoflurane group (n = 22,
      received 2% sevoflurane for 5 h) and parecoxib group (n = 22, received
      intraperitoneal injections of 10 mg/kg parecoxib and then exposed to 2%
      sevoflurane for 5 h). Spatial learning performance was tested by Morris water
      maze. The expression of cyclooxygenase-2 protein and ultrastructure of synapse in
      hippocampus were measured. RESULTS: Sevoflurane anesthesia impaired the spatial
      learning and memory in aged rats. Compared with sevoflurane group, parecoxib
      group showed shorter escape latency and more number of crossings over the
      previous platform area. Furthermore, parecoxib treatment also significantly
      prevented the synaptic changes induced by sevoflurane. CONCLUSION: Parecoxib
      mitigates spatial memory impairment induced by sevoflurane anesthesia in aged
      rats. The synaptic morphometry change may be one of the mechanisms involved in
      learning and memory deficit.

PMID- 22409587
TI  - Treatment of coronary bifurcation lesions with drug-eluting stents: insights from
      the first phase of the prospective multicenter german drug-eluting stent
      registry.
AB  - BACKGROUND: Controversy exists about the impact of treating bifurcations on
      overall outcome of coronary interventions using drug-eluting stents (DES). We
      sought to investigate 1-year outcome of the treatment of bifurcation lesions
      using DES in a large "real-world" cohort. METHODS AND RESULTS: Among 5,126
      patients enrolled in phase I of the multicenter German Drug-Eluting Stent
      Registry, 814 (16%) were treated for a bifurcation lesion. Patients with
      bifurcations were compared to those without bifurcations in terms of baseline
      characteristics, major adverse cardiac and cerebrovascular events (MACCE) and
      target vessel revascularization (TVR) at 1 year. Usage of sirolimus-eluting
      stents (SES) versus paclitaxel-eluting stents (PES) was also evaluated. In total,
      1,021 and 5,189 stents were implanted in the bifurcation (1.25 stents/patient)
      and nonbifurcation (1.2 stents/patient) group, respectively, but 64.5% of
      bifurcation lesions were treated with a single stent. More complex lesion and
      procedural characteristics were observed in the bifurcation group. However, there
      was no difference in 1-year MACCE rates (a composite of death, myocardial
      infarction, and stroke) between the bifurcation group and nonbifurcation group
      (8.1% vs. 8.3%, P = 0.85). Rates of TVR (11.2% vs. 10.8%, P = 0.75) and Academic
      Research Consoritum-defined definite stent thrombosis (0.9% vs. 0.8%, P = 0.67)
      were also comparable. MACCE and TVR rates remained similar after adjustment for
      differences in baseline characteristics. MACCE and TVR in SES patients were 7.2%
      and 12.6% versus 8.7% and 10.2% in PES patients (P = 0.46 and P = 0.30,
      respectively). CONCLUSION: In this large multicenter registry, treatment of
      bifurcation lesions with DES appears effective and safe. The presence of
      bifurcations did not affect 1-year outcomes after DES implantation. The outcomes
      for SES and PES were similar.

PMID- 22409588
TI  - Traumatic palatal perforation after orotracheal intubation: a case report and a
      review of the literature.
AB  - In this report, we describe an unusual case of a traumatic palatal perforation
      caused by orotracheal intubation. The paucity of reports of palatal perforation
      resulting from intubation in the literature suggests that it is a rare
      occurrence. However, recognizing this potential complication and managing the
      airway appropriately may reduce patient morbidity. 

PMID- 22409589
TI  - Liquid crystal mediated interactions between nanoparticles in a nematic phase.
AB  - A continuum theory is used to study the interactions between nanoparticles
      suspended in nematic liquid crystals. The free energy functional that describes
      the system is minimized using an Euler-Lagrange approach and an unsymmetric
      radial basis function method. It is shown that nanoparticle liquid-crystal
      mediated interactions can be controlled over a large range of magnitudes through
      changes of the anchoring energy and the particle diameter. The results presented
      in this work serve to reconcile past discrepancies between theoretical
      predictions and experimental observations, and suggest intriguing possibilities
      for directed nanoparticle self-assembly in liquid crystalline media.

PMID- 22409590
TI  - A pilot study on the effects of S-equol compared to soy isoflavones on menopausal
      hot flash frequency.
AB  - BACKGROUND: S-equol, a metabolite of the soy isoflavone daidzein, has been
      proposed as having potential for relief of menopausal symptoms. This study
      compared the efficacy of the natural S-equol supplement, SE5-OH, with isoflavones
      for relieving hot flashes and other menopausal symptoms. METHODS: An 8-week
      randomized, double-blind, active comparator trial with SE5-OH was conducted in
      postmenopausal women (aged 45-65 years), who experienced >=5 hot flashes/day.
      Participants (n=102) were assigned to one of four treatment groups: 10 (n=24), 20
      (n=27), or 40 (n=25) mg S-equol/day or soy isoflavones (n=26). Participants
      recorded their hot flash frequency and rated their menopause symptom severity.
      RESULTS: Reductions in hot flash frequency at week 8 were similar for all
      treatment groups. However, based on analyses of the cumulative effect for the 8
      week period, 40 mg/day S-equol had a greater reduction of hot flash frequency
      compared to isoflavones (p=0.021). A subgroup analysis further indicated that for
      subjects with >8 hot flashes/day at baseline, 20 and 40 mg/day S-equol were
      superior to isoflavones in reducing hot flash frequency (p=0.045 and p=0.001,
      respectively). In addition, 10 and 20 mg/day S-equol improved muscle and joint
      pain score compared with isoflavones (p=0.003 and p=0.005, respectively).
      CONCLUSIONS: S-equol, 10 mg/day, appears to be as effective as soy isoflavones at
      reducing hot flash frequency and more effective for relieving muscle and joint
      pain in postmenopausal women. S-equol, >=20 mg/day, alleviates hot flashes to a
      greater extent than soy isoflavones in those women who experience >8 hot
      flashes/day.

PMID- 22409591
TI  - Recent progress using high-throughput sequencing technologies in plant molecular
      breeding.
AB  - High-throughput sequencing is a revolutionary technological innovation in DNA
      sequencing. This technology has an ultra-low cost per base of sequencing and an
      overwhelmingly high data output. High-throughput sequencing has brought novel
      research methods and solutions to the research fields of genomics and post
      genomics. Furthermore, this technology is leading to a new molecular breeding
      revolution that has landmark significance for scientific research and enables us
      to launch multi-level, multi-faceted, and multi-extent studies in the fields of
      crop genetics, genomics, and crop breeding. In this paper, we review progress in
      the application of high-throughput sequencing technologies to plant molecular
      breeding studies.

PMID- 22409592
TI  - Design of ionic liquid 3-methyl-1-sulfonic acid imidazolium nitrate as reagent
      for the nitration of aromatic compounds by in situ generation of NO(2) in acidic
      media.
AB  - 3-Methyl-1-sulfonic acid imidazolium nitrate ([Msim]NO(3)) as a new Bronsted
      acidic ionic liquid and nitrating agent was prepared and used for the efficient
      nitration of aromatic compounds (even aniline derivatives). The dramatic effect
      of this reagent by in situ generation of nitrogen dioxide as a radical on
      aromatic compounds to give nitroarenes has been studied.

PMID- 22409593
TI  - Microfluidic digital isoelectric fractionation for rapid multidimensional
      glycoprotein analysis.
AB  - Here we present an integrated microfluidic device for rapid and automated
      isolation and quantification of glycoprotein biomarkers directly from biological
      samples on a multidimensional analysis platform. In the first dimension, digital
      isoelectric fractionation (dIEF) uses discrete pH-specific membranes to separate
      proteins and their isoforms into precise bins in a highly flexible spatial
      arrangement on-chip. dIEF provides high sample preconcentration factors followed
      by immediate high-fidelity transfer of fractions for downstream analysis. We
      successfully fractionate isoforms of two potential glycoprotein cancer markers,
      fetuin and prostate-specific antigen (PSA), with 10 min run time, and results are
      compared qualitatively and quantitatively to conventional slab gel IEF. In the
      second dimension, functionalized monolithic columns are used to capture and
      detect targeted analytes from each fraction. We demonstrate rapid two-dimensional
      fractionation, immunocapture, and detection of C-reactive protein (CRP) spiked in
      human serum. This rapid, flexible, and automated approach is well-suited for
      glycoprotein biomarker research and verification studies and represents a
      practical avenue for glycoprotein isoform-based diagnostic testing.

PMID- 22409594
TI  - JAIBA, a class-II HD-ZIP transcription factor involved in the regulation of
      meristematic activity, and important for correct gynoecium and fruit development
      in Arabidopsis.
AB  - The gynoecium is one of the most complex organs of a plant. After fertilization,
      it becomes a fruit, which has two important functions: to protect the seeds while
      they develop and to disperse them at maturity. The development and patterning of
      the gynoecium and later fruit must be finely regulated to ensure the survival of
      the species that produces them. The process that leads to successful fruit
      formation starts at early stages of floral meristem development and follows a
      series of chronologically successive events. In this work we report the
      functional characterization of the class-II homeodomain leucine zipper (HD-ZIP)
      JAIBA (JAB) gene. Mutant jab plants show sporophytic defects in male and female
      reproductive development, and combined with crabs claw cause defects in the
      floral meristem (FM) determination process and gynoecium medial tissue
      development. This suggests that proper FM determination is required for gynoecium
      medial tissue development, and indicates that JAB and CRC are necessary for both
      processes. Furthermore, the JAB protein interacts with transcription factors
      known to regulate meristematic activity, fruit development, and floral meristem
      determinacy. The sporophytic effect on pollen and embryo sac development might be
      an independent and later function of JAB. In summary, we present data that
      indicates that the JAB gene regulates meristematic activity in different tissues,
      and that it is necessary for the correct formation of the gynoecium at different
      stages, contributing to a crucial process in plant life: proper fruit
      development.

PMID- 22409595
TI  - Breast reconstruction in patients with personal and family history of breast
      cancer undergoing contralateral prophylactic mastectomy, a 10-year experience.
AB  - BACKGROUND: The purpose of this study was to evaluate the clinical course of
      breast reconstruction in patients with personal and family history of breast
      cancer undergoing contralateral prophylactic mastectomy (CPM) and elucidate the
      association between reoperation risk and adjuvant treatment. METHODS: A
      descriptive retrospective study of a consecutive series of breast cancer patients
      who underwent CPM with breast reconstruction at Karolinska University Hospital
      between 1998 and 2008 was performed. Reoperation was chosen as an outcome
      variable assessing morbidity and thus documented for each patient and for each
      reconstructed breast. Regression analyses were performed to evaluate the risk of
      reoperation after bilateral breast reconstruction. RESULTS: Ninety-one patients
      underwent CPM during the study period. Their mean age at CPM was 45.3 years (SD
      =9.4). No contralateral breast cancer was diagnosed after CPM during the median
      follow-up period of 3.9 years. All women, but two, received an implant based
      breast reconstruction. The majority (n =75, 82%) underwent CPM with concurrent
      bilateral breast reconstruction. Overall, after bilateral breast reconstruction
      45/75 (60%) required at least one reoperation on the CPM side (n =2, 3%),
      therapeutic mastectomy (TM) side (n =17, 23%) or both sides (n =26, 33%). In the
      paired analyses, the probability of reoperation was significantly higher after TM
      reconstruction as compared to CPM (0.57 vs. 0.37, p =0.001). The mean number of
      reoperations required for completion of TM and CPM reconstruction was 0.84 and
      0.49, respectively (p =0.003). Among all potential risk factors, only
      radiotherapy was associated with reoperation after bilateral breast
      reconstruction (odds ratio [OR]: 4.2, 95% CI, 1.3 to 13.6, p =0.015).
      CONCLUSIONS: Breast reconstruction in patients with personal and family history
      of breast cancer is a complex operation. This study found that the clinical
      course after bilateral breast reconstruction was predominantly affected by
      reoperations on the TM side and given radiotherapy was associated with
      reoperation. Further studies are necessary to examine the possible predictors of
      unanticipated reoperations in candidates for CPM with breast reconstruction.

PMID- 22409596
TI  - Ultrasound guidance allows faster peripheral IV cannulation in children under 3
      years of age with difficult venous access: a prospective randomized study.
AB  - OBJECTIVES: Ultrasound-guided peripheral venous access (USG-PIVA) presents many
      advantages over the reference 'blind' technique in both adults and children in
      emergency situations. AIM: To compare USG-PIVA with the blind technique in
      children <3 years undergoing general anesthesia. METHODS: After obtaining the
      approval of the ethics committee and informed consent from the parents, we
      included all children <3 years scheduled to undergo general anesthesia [surgery,
      magnetic resonance imaging (MRI)], who presented difficult venous access. The
      children were randomized into two groups: the US group (USG-PIVA) and the B group
      (blind). The primary endpoint was time to cannulation (from tourniquet placement
      to successful IV cannulation), compared between USG-PIVA group and B group by
      intention-to-treat analysis. Secondary outcomes were success rate at the first
      puncture, number of punctures, and diameter of the catheters. Cannulations
      requiring >15 min were considered as failures. In case of failure in group B, USG
      PIVA was attempted for a further 15 min. RESULTS: Twenty children were included
      in each group. Groups were comparable for sex, age, and BMI. Significant
      differences were observed in median time to cannulation (63.5 s vs 420.5 s, USG
      PIVA vs B respectively, P < 0.001); median number of punctures (1 vs 2.5, USG
      PIVA vs B, P = 0.004); and success rate at first cannulation (85% vs 35%, USG
      PIVA vs B, P = 0.0012). In contrast, overall success rate did not differ
      significantly between groups (90% vs 85%, USG-PIVA vs B, P = 0.63). CONCLUSIONS:
      Ultrasound-guided peripheral venous access leads to faster peripheral IV access
      and should therefore be recommended in children presenting with difficult venous
      access.

PMID- 22409597
TI  - Alternative sigma factor sigmaH activates competence gene expression in
      Lactobacillus sakei.
AB  - BACKGROUND: Alternative sigma factors trigger various adaptive responses.
      Lactobacillus sakei, a non-sporulating meat-borne bacterium, carries an
      alternative sigma factor seemingly orthologous to sigma(H) of Bacillus subtilis,
      best known for its contribution to the initiation of a large starvation response
      ultimately leading to sporulation. As the role of sigma(H)-like factors has been
      little studied in non-sporulating bacteria, we investigated the function of
      sigma(H) in L. sakei. RESULTS: Transcription of sigH coding for sigma(H) was
      hardly affected by entry into stationary phase in our laboratory conditions.
      Twenty-five genes potentially regulated by sigma(H) in L. sakei 23 K were
      revealed by genome-wide transcriptomic profiling of sigH overexpression and/or
      quantitative PCR analysis. More than half of them are involved in the synthesis
      of a DNA uptake machinery linked to genetic competence, and in DNA metabolism;
      however, sigma(H) overproduction did not allow detectable genetic transformation.
      sigma(H) was found to be conserved in the L. sakei species. CONCLUSION: Our
      results are indicative of the existence of a genetic competence state activated
      by sigma(H) in L. sakei, and sustain the hypothesis that sigma(H)-like factors in
      non sporulating Firmicutes share this common function with the well-known ComX of
      naturally transformable streptococci.

PMID- 22409598
TI  - Mechanism-based inactivation (MBI) of cytochrome P450 enzymes: structure-activity
      relationships and discovery strategies to mitigate drug-drug interaction risks.

PMID- 22409599
TI  - Effects of dietary supplementation of fermented garlic powder on growth
      performance, apparent total tract digestibility, blood characteristics and faecal
      microbial concentration in weanling pigs.
AB  - A total of 144 weanling pigs (5.5 +/- 0.42 kg) were used in a 5-week trial to
      evaluate the effect of fermented garlic powder (FGP) supplementation in weaning
      pigs. Pigs were randomly allocated to the following four dietary treatments: (i)
      control (CON; basal diet), (ii) FGP0.5 (CON + 0.5 g/kg FGP), (iii) FGP1 (CON + 1
      g/kg FGP), (iv) FGP2 (CON + 2 g/kg FGP). There were six replications with six
      pigs (three barrows and three gilts) per pen. Pigs fed FGP0.5 treatments
      increased (p < 0.05) average daily gain (ADG) and average daily feed intake
      (ADFI) during 3-5 and 0-5 week. No difference was observed on gain/ feed (G/F)
      ratio in this study. The inclusion of FGP1 and FGP2 treatments increased DM (p <
      0.05) digestibility compared with the CON treatment throughout the experiment.
      The apparent total tract digestibility of N was (p < 0.05) increased by the
      dietary FGP throughout the experiment. Pigs fed FGP1 and FGP2 treatments
      increased the lymphocyte concentration (p < 0.05) and RBC concentration compared
      with the CON group. Dietary FGP decreased the blood total cholesterol (p < 0.05)
      in comparison with the CON group. The triglyceride (p < 0.05) concentration was
      decreased in FGP1 and FGP2 treatments compared with those in the CON treatment at
      the end of the experiment. Pigs fed FGP1 and FGP2 treatments had a lower number
      of Escherichia coli in faeces on 21 (p < 0.05) and 35 days (p = 0.05) than those
      in the CON treatment. In conclusion, dietary fermented garlic powder (0.5 g/kg)
      can improve ADG and ADFI in weanling pigs, but not at higher levels (1 and 2
      g/kg). Dietary fermented garlic powder can also increase the nutrient
      digestibility, lymphocytes and RBC concentrations, but decrease the faecal E.
      coli concentration in weaning pigs.

PMID- 22409600
TI  - Palladium-catalyzed one-pot diarylamine formation from nitroarenes and
      cyclohexanones.
AB  - The first palladium-catalyzed diarylamine formation from nitroarenes and
      cyclohexanone derivatives using borrowed hydrogen is described. Various
      diarylamines were selectively obtained in good to excellent yields. The reaction
      tolerated a wide range of functionalities. The nitro reduction, cyclohexanone
      dehydrogenation, and imine formation and reduction were realized in a cascade
      without an external reducing reagent and oxidant.

PMID- 22409601
TI  - The structure of savant calendrical knowledge.
AB  - AIM: We aimed to explore the organization of the calendar knowledge base
      underlying date calculation by assessing the ability of savant calendar
      calculators to free recall a series of date lists. METHOD: Four experiments are
      reported that assessed recall of structural and non-structural features of the
      calendar in eight savant calendar calculators (seven males; one female; median
      age 34 y 6 mo; age range 27-47 y), five of whom had a diagnosis on the autism
      spectrum. The inclusion criterion was a genuine calculation ability rather than
      an interest in dates. RESULTS: Mean recall was facilitated for material organized
      according to the structural features of a calendar (leap years, dates falling on
      the same weekday, dates occurring at 28 y intervals) but not for a non-structural
      calendar feature (Easter Sunday). INTERPRETATION: Distinctions are drawn between
      two sources of savant calendar-related knowledge, structural and event related.
      It has been suggested that structural knowledge plays a key role in the
      acquisition and operation of savant date calculation skills.

PMID- 22409602
TI  - Chromosome 15q21-22-related polymorphisms and haplotypes are associated with
      susceptibility to type-2 diabetic nonproliferative retinopathy.
AB  - OBJECTIVE: Diabetic retinopathy (DR) is a microvascular complication of diabetes
      with a complex multifactorial pathogenesis. We aimed to investigate whether
      chromosome 15q21-22-related gene polymorphisms could be used as markers of DR
      susceptibility in type 2 diabetic (T2D) individuals. METHODS: Individuals were
      divided into three groups: (1) T2D with nonproliferative DR (NPDR; n=102); (2)
      T2D with proliferative DR (PDR; n=72); (3) T2D without DR (n=573). Six single
      nucleotide polymorphisms (SNPs) (rs7174997, rs3751624, rs8025011, rs17818837,
      rs2922220, and rs2414520) lying within chromosome 15q21-22 region were genotyped
      by using Illumina HumanHap550-Duo BeadChips. Genotypes/allelic frequencies and
      haplotypes for these polymorphisms in each group were compared. RESULTS: The
      MYO5C related SNP (rs3751624)*A related genotype and allele are associated with
      higher susceptibilities to DR, including PDR and NPDR. The rs3751624*GG/AA+AG
      percentages in each group are (1) 75.5%/24.5%, (2) 73.6%/26.4%, and (3)
      82.5%/17.5%. In contrast, the other five SNPs in each group were not
      significantly different. One haplotype (G-A-G-G-T-G) appears significantly
      different between T2D individuals with and without DR. Other haplotype
      distributions were not significantly different between each group. CONCLUSION:
      The MYO5C related SNP (rs3751624)*A related genotype/allele and haplotype (G-A-G
      G-T-G) might be associated with susceptibility for retinopathy in T2D
      individuals. Some chromosome 15q21-22* related genetic variations might
      contribute to the pathogenesis of DR.

PMID- 22409603
TI  - Kinematic analysis of three water polo front crawl styles.
AB  - During water polo matches, players use different front crawl styles. The purpose
      of this study was to conduct a kinematic analysis of three water polo front crawl
      styles: front crawl with head under water, front crawl with head above water, and
      front crawl when leading the ball. Ten proficient water polo players performed 3
      * 15 m sprints in each front crawl style, which were recorded three-dimensionally
      by two surface and four underwater cameras. The results showed no differences in
      performance and several kinematic characteristics among the water polo front
      crawl styles. However, front crawl when leading the ball showed shorter stroke
      length and greater stroke frequency. Front crawl with head underwater presented
      greater maximal finger depth and elbow angle at mid-stroke position. Front crawl
      with head above water and when leading the ball showed greater trunk obliquity
      and maximal depth of right and left foot, and shorter kick stroke frequency. The
      findings suggest that proficient players learn to master front crawl with head
      above water to achieve top velocity. Despite the common use of the front crawl
      with head underwater as the basis for water polo fast displacement, coaches
      should emphasize the use of the specific water polo styles to attain high
      performance.

PMID- 22409604
TI  - Magnesium azaphthalocyanines: an emerging family of excellent red-emitting
      fluorophores.
AB  - Magnesium(II), zinc(II), and metal-free phthalocyanines (Pcs) and
      azaphthalocyanines (AzaPcs) containing alkylsulfanyl, aryloxy, and dialkylamino
      peripheral substituents have been synthesized. The complexation of magnesium(II)
      by metal-free Pcs and AzaPcs has been studied in detail to determine the optimal
      reaction conditions necessary to ensure a complete conversion. Photophysical and
      photochemical measurements in tetrahydrofuran showed that magnesium(II) AzaPcs
      with aryloxy and alkylsulfanyl substituents have excellent fluorescent properties
      (Phi(F) up to 0.73) and that the corresponding zinc(II) Pcs are efficient singlet
      oxygen producers (Phi(Delta) up to 0.68). The presence of dialkylamino
      substituents causes intramolecular charge transfer within the molecule that
      competes with fluorescence and singlet oxygen formation. Alkylsulfanyl MgAzaPc
      and ZnAzaPc were the most photostable compounds among the series of studied
      derivatives. In addition, high molar absorption coefficients (epsilon ~ 300,000
      M(-1) cm(-1)), absorption (lambda(max) ~ 650 nm), and emission (lambda(em) ~ 660
      nm, high Phi(F)) in the red region suggest that these molecules are potential
      fluorescent probes that are superior to the commercial red cyanine dye Cy5.
      MgAzaPc, when incorporated into lipidic bilayers of liposomes, maintains
      excellent fluorescence properties (Phi(F) = 0.64). Water-soluble MgAzaPc with
      quaternary ammonium peripheral substituents retained a high fluorescence quantum
      yield even in water (Phi(F) = 0.25). The described properties show that
      magnesium(II) AzaPcs are excellent red-emitting fluorophores with potential
      applications as fluorescent probes in sensing or in vitro imaging applications.

PMID- 22409605
TI  - Celluloid devils: a research study of male nurses in feature films.
AB  - AIM: To report a study of how male nurses are portrayed in feature films.
      BACKGROUND: It was hypothesized that male nurses are frequently portrayed
      negatively or stereotypically in the film media, potentially having a negative
      impact on male nurse recruitment and the public's perception of male nurses.
      DESIGN/METHODS: An interpretive, qualitative methodology guided by insights into
      hegemonic masculinity and structured around a set of collective case studies
      (films) was used to examine the portrayal of male nurses in feature films made in
      the Western world from 1900 to 2007. Over 36,000 feature film synopses were
      reviewed (via CINAHL, ProQuest and relevant movie-specific literature) for the
      keyword 'nurse' and 'nursing' with an additional search for films from 1900 to
      2010 for the word 'male nurse'. Identified films were labelled as 'cases' and
      analysed collectively to determine key attributes related to men in nursing and
      explore them for the emergence of concepts and themes related to the image of
      male nurses in films. RESULTS/FINDINGS: A total of 13 relevant cases (feature
      films) were identified with 12 being made in the USA. Most films portrayed male
      nurses negatively and in ways opposed to hegemonic masculinity, as effeminate,
      homosexual, homicidal, corrupt or incompetent. Few film images of male nurses
      show them in traditional masculine roles or as clinically competent or self
      confident professionals. CONCLUSION:   Feature films predominantly portray male
      nurses negatively. Given the popularity of feature films, there may be negative
      effects on recruitment and on the public's perception of male nurses.

PMID- 22409606
TI  - Stabilizing gold adatoms by thiophenyl derivatives: a possible route toward metal
      redispersion.
AB  - Tris(phenylthio)benzene molecules have been synthesized in order to explore their
      ability to trap single Au adatoms on an Au(111) surface. The resulting metal
      organic complexes have been characterized with low-temperature scanning tunneling
      microscopy and infrared reflection absorption spectroscopy; possible structure
      models have been derived from density functional calculations. Upon room
      temperature deposition, the thiophenyl derivatives form dimer structures,
      comprising two molecules and six Au adatoms. Below 100 K, isolated molecules are
      found as well that have trapped up to six Au atoms. On the basis of the
      experimental results and calculated formation energies of the complexes, we
      discuss potential applications of the thioethers for the redispersion of metals
      on a catalyst surface. First experiments performed on Au particle ensembles
      prepared on alumina thin films suggest that the molecular ligands are indeed able
      to change the distribution of gold on the oxide surface.

PMID- 22409607
TI  - Introduction. Promoting evidence-informed practice.

PMID- 22409608
TI  - Building organizational supports for knowledge sharing in county human service
      organizations: a cross-case analysis of works-in-progress.
AB  - Building on the literature related to evidence-based practice, knowledge
      management, and learning organizations, this cross-case analysis presents twelve
      works-in-progress in ten local public human service organizations seeking to
      develop their own knowledge sharing systems. The data for this cross-case
      analysis can be found in the various contributions to this Special Issue. The
      findings feature the developmental aspects of building a learning organization
      that include knowledge sharing systems featuring transparency, self-assessment,
      and dissemination and utilization. Implications for practice focus on the
      structure and processes involved in building knowledge sharing teams inside
      public human service organizations.

PMID- 22409609
TI  - Data mining in children and family services: the Contra Costa County experience.
AB  - Despite access to a comprehensive administrative database that would allow for
      timely data retrieval and utilization, regular use of data to inform service
      provision remained infrequent at one children and family services agency. To
      address this issue, a research and evaluation manager was hired to facilitate
      regular data use and evidence-informed service provision. This led to a shift in
      agency culture that moved from viewing data collection as a burden and threat, to
      now valuing data as a powerful tool for improving programs and outcomes for
      children and families. This case study presents the experiences of this agency,
      describing the process by which the research and evaluation manager was hired,
      how data are now used by the agency, significant changes resulting from the
      agency's new data use practices, and perspectives of the evaluator and staff on
      data use and changes in agency culture.

PMID- 22409611
TI  - Linking an agency strategic review to increase knowledge management: San
      Francisco County Human Service Agency.
AB  - Led by the agency director, the agency engaged in a Strategic Review, based on a
      comprehensive assessment of agency performance that identified strategies to
      improve organizational effectiveness through increased data-informed practice and
      knowledge management. The Strategic Review gathered information on staff
      perceptions, perceptions of external stakeholders, changing citywide and
      neighborhood demographics, policy mandates, and budget and workload issues. The
      need for the review was based upon multiple, substantial changes not addressed in
      the 2000 Strategic Plan, including the 2004 merger of the Department of Human
      Services and the Department of Aging and Adult Services, changes among the
      executive management team, transitions among key political entities, new policy
      mandates and changing budget allocations. This case study describes the Strategic
      Review process and content, summarizing key challenges and lessons related to
      addressing workload demands, fostering positive staff attitudes, balancing
      internal and external information needs, and integrating data use and planning
      processes across the agency.

PMID- 22409610
TI  - Building a culture of learning through organizational development: the
      experiences of the Marin County Health and Human Services Department.
AB  - After determining a need for organizational change informed by changes in
      workforce demographics, community demographics, the socio-political and economic
      environment, and constraints on resources, one agency sought to transform its
      organizational culture into that of a learning organization. An external
      organizational development consultant was hired to work with agency leadership to
      identify ways that would help move the agency's culture towards one that was
      conducive to learning. Specifically, the agency director sought to create a
      culture where communication is encouraged both vertically and horizontally,
      frontline level workers are engaged and their voices heard, cross-departmental
      problem solving is practiced, innovative ideas are supported, and evidence
      informed practice regularly implemented. This case study describes the
      experiences of this agency and the process taken toward engaging an external
      consultant and moving towards the development of a culture of learning.

PMID- 22409612
TI  - Linking departmental priorities to knowledge management: the experiences of Santa
      Cruz County's Human Services Department.
AB  - Federal welfare reform, local service collaborations, and the evolution of
      statewide information systems inspired agency interest in evidence-informed
      practice and knowledge sharing systems. Four agency leaders, including the
      Director, Deputy Director, Director of Planning and Evaluation, and Staff
      Development Program Manager championed the development of a learning organization
      based on knowledge management throughout the agency. Internal department
      restructuring helped to strengthen the Planning and Evaluation, Staff
      Development, and Personnel units, which have become central to supporting
      knowledge sharing activities. The Four Pillars of Knowledge framework was
      designed to capture agency directions in relationship to future knowledge
      management goals. Featuring People, Practice, Technology and Budget, the
      framework links the agency's services, mission and goals to the process of
      becoming a learning organization. Built through an iterative process, the
      framework was created by observing existing activities in each department rather
      than being designed from the top down. Knowledge management can help the
      department to fulfill its mission despite reduced resources.

PMID- 22409613
TI  - Using evidence-based accreditation standards to promote continuous quality
      improvement: the experiences of the San Mateo County Human Services Agency.
AB  - Following a difficult period of service provision, an agency determined that
      drastic changes were needed to improve agency-wide capacity and functioning. The
      agency engaged in an organizational level self-assessment aimed at identifying
      areas for improvement and beginning work towards determining professional
      standards for service. Results of this organizational self-assessment paved the
      way for pursuing accreditation of its services, and the agency became the first
      public agency in its state to be accredited by the Council on Accreditation in
      all eligible services. This case study describes this agency's efforts in
      engaging in an organizational self-assessment, the analysis and codification of
      their practices, and their eventual development of a systematized process for
      capturing, evaluating and improving practice.

PMID- 22409614
TI  - Transforming data into action: the Sonoma County Human Services Department.
AB  - In order to centralize data-based initiatives, the Director of the Department
      worked with the Board of Supervisors and the executive team to develop a new
      Planning, Research, and Evaluation (PRE) division. PRE is establishing rules for
      data-based decision making and consolidating data collection to ensure quality
      and consistency. It aims to target resources toward visionary, pro-active program
      planning and implementation, and inform the public about the role of Human
      Services in creating a healthy, safe and productive environment. PRE staff spent
      several months studying the job functions of staff, to determine how they use
      information to inform practice, consulting other counties about their
      experiences. The PRE team developed Datascript, outlining two agency aims: (a)
      foster a decision-making environment that values and successfully uses empirical
      evidence for strategic change, and (b) manage the role and image of the Human
      Services Department in the external environment. The case study describes action
      steps developed to achieve each aim.

PMID- 22409615
TI  - Knowledge capture and the retirement of the director of finance: succession
      planning in the San Mateo County Human Services Agency.
AB  - Concern over the impending retirement of several top-level managers led a county
      agency to engage in efforts aimed at more efficient succession management.
      Administrators developed plans to prevent the loss of invaluable knowledge and
      wisdom accompanying retirement of experienced agency leaders. The agency's
      Director of Finance (DoF) was one of the first key figures projected to retire,
      and a succession plan was implemented to transfer his knowledge for use after his
      departure. The knowledge transfer process involved three stages, including: (1)
      employing the DoF as teacher, having him develop curricula and conduct trainings;
      (2) engaging the DoF as mentor, allowing an existing staff member and the DoF's
      successor to shadow and be coached by the DoF; and (3) developing a knowledge
      management system that could be used after the DoF departed. This case study
      describes the knowledge transfer process and experiences shared by the DoF and
      this agency.

PMID- 22409616
TI  - A senior manager with a knowledge management portfolio: the Santa Clara County
      experience.
AB  - The agency director sought to create a systematically coordinated department that
      utilizes knowledge management strategies to promote evidence-informed practice.
      In his view, the organization was not providing needed information or
      organizational supports for practitioners to use knowledge effectively. To
      address this issue, he created a Director of Development and Operational Planning
      (DDOP) position with the responsibility to build structures and facilitate
      processes that support knowledge management. The DDOP oversees research and
      planning, government relations, legislative development and support, Board of
      Supervisors communications, staff development and training, community contracts,
      public information and in-house communication. The DDOP is reorganizing units
      under her supervision to create a knowledge management matrix that will implement
      new knowledge sharing strategies related to evaluation, contracts, legislation,
      organizational development, policy and planning, and staff development. The case
      study describes challenges and strategies related to: government regulations,
      size and complexity of the agency, staff resistance, and the developmental nature
      of the process.

PMID- 22409617
TI  - Quality management as knowledge sharing: experiences of the Napa County Health
      and Human Services Agency.
AB  - Lacking a coordinated effort in utilizing data and tracking program outcomes, one
      agency developed a Quality Management (QM) division to facilitate and manage more
      effective data use. To support this process, the agency sought to develop a
      collective, agency-wide understanding and investment in improving and measuring
      client outcomes. Similarly, the agency also focused efforts on creating a culture
      of transparency and accountability, with goals of improving service, increasing
      agency integrity, meeting regulatory compliance, and engaging in effective risk
      management. Operationalizing the QM initiative involved developing procedures,
      systems, and guidelines that would facilitate the generation of reliable and
      accurate data that could be used to inform program change and decision-making.
      This case study describes this agency's experience in successfully creating and
      implementing a QM initiative aimed at engaging in greater knowledge sharing.

PMID- 22409618
TI  - Learning from staff to share knowledge and inform decision-making: the Contra
      Costa County experience.
AB  - In an effort to increase staff engagement and opportunities for greater two-way
      communication between managers and staff, a strategic plan was developed
      involving administration of an agency-wide staff satisfaction survey. A
      comprehensive survey was administered to nearly 1700 employees throughout the
      agency, which encompasses several diverse bureaus ranging from child and family
      services, aging and adult services, and a workforce investment board. The online
      survey included 36 questions aimed at gathering staff perspectives on job
      satisfaction, work expectations, supervision, and information sharing within the
      agency. 825 employees responded to the survey, and findings were analyzed and
      shared agency-wide. Results of the survey have been used to inform ongoing agency
      change and to facilitate continued engagement of staff in organizational goals
      and initiatives.

PMID- 22409619
TI  - The use of key indicators as a foundation for knowledge management: the
      experiences of Monterey County's Social and Employment Services Department.
AB  - While effective knowledge management practices are commonly sought by
      organizations, facilitating the use and ongoing engagement in these practices can
      be challenging. To this end, one agency developed a strategy for
      institutionalizing their knowledge management functions by appointing a team
      responsible for monitoring and implementing knowledge management functions, and
      creating a report for use as a tool by departments agency-wide. Aimed at
      increasing transparency both within the agency and with the surrounding
      community, the report provides an overview of individual departments' programs,
      goals, recent caseload trends, and latest achievements. The report is made
      available online and accessible by the general public. This case study describes
      the development of this team and report, as well as lessons learned and future
      knowledge management goals for the agency.

PMID- 22409620
TI  - Using agency-wide dashboards for data monitoring and data mining: the Solano
      County Health and Social Services Department.
AB  - The Director needed accessible data on critical program areas in order to monitor
      changes presenting potential negative impacts. The Research, Evaluation and
      Planning division spearheaded the Dashboard featuring the seven program areas
      (Employment & Eligibility, Child Welfare Services, Mental Health, Public Health,
      Older Disabled Adult Services, Substance Abuse, and the Special Investigations
      Bureau), and three administrative units. Deputy Directors specified several key
      areas that their divisions were mandated to report or viewed as important for
      monitoring. The Dashboard enables Directors to communicate internally and
      externally about program results, strengths and growth areas, as well as track
      progress in relationship to strategic plan initiatives and intervene in areas
      needing improvement. Executive team members identify critical areas for
      improvement and the Assistant Director for Research and Evaluation implements
      corrective action through the Quality Assurance Committee. Agency lessons relate
      to the importance of automation, data interpretation, and team members'
      understanding of the indicators, related practice strategies, and contextual
      factors.

PMID- 22409621
TI  - Building organizational supports for research-minded practitioners.
AB  - One of the biggest challenges facing human service organizations is the
      proliferation of information from inside and outside the agency that needs to be
      managed if it is to be of use. The concepts of tacit and explicit knowledge can
      inform an approach to this challenge. Tacit knowledge is stored in the minds of
      practitioners (often called practice wisdom) and the explicit knowledge is often
      found in organizational procedure manuals and educational and training materials.
      Building on this perspective, this analysis provides a preliminary definition of
      research-minded practitioners by explicating the elements of curiosity, critical
      reflection, and critical thinking. The organizational implications of developing
      a cadre of research-minded practitioners include the commitment of top management
      to support "link officers", evidence request services, research and development
      units, and service standards. The challenges include the capacity to
      identify/support research-minded practitioners, promote an organizational culture
      of evidence-informed practice, redefine staff development and training, redefine
      job descriptions, and specify the nature of managerial leadership.

PMID- 22409622
TI  - Maintaining the structure of templated porous materials for reactive and high
      temperature applications.
AB  - Nanoporous and nanostructured materials are becoming increasingly important for
      advanced applications involving, for example, bioactive materials, catalytic
      materials, energy storage and conversion materials, photonic crystals, membranes,
      and more. As such, they are exposed to a variety of harsh environments and often
      experience detrimental morphological changes as a result. This article highlights
      material limitations and recent advances in porous materials--three-dimensionally
      ordered macroporous (3DOM) materials in particular--under reactive or high
      temperature conditions. Examples include systems where morphological changes are
      desired and systems that require an increased retention of structure, surface
      area, and overall material integrity during synthesis and processing. Structural
      modifications, changes in composition, and alternate synthesis routes are
      explored and discussed. Improvements in thermal or structural stability have been
      achieved by the isolation of nanoparticles in porous structures through spatial
      separation, by confinement in a more thermally stable host, by the application of
      a protective surface or an adhesive interlayer, by alloy or solid solution
      formation, and by doping to induce solute drag.

PMID- 22409623
TI  - Probing the Ca(2+) switch of the neuronal Ca(2+) sensor GCAP2 by time-resolved
      fluorescence spectroscopy.
AB  - We report fluorescence lifetime and rotational anisotropy measurements of the
      fluorescent dye Alexa647 attached to the guanylate cyclase-activating protein 2
      (GCAP2), an intracellular myristoylated calcium sensor protein operating in
      photoreceptor cells. By linking the dye to different protein regions critical for
      monitoring calcium-induced conformational changes, we could measure fluorescence
      lifetimes and rotational correlation times as a function of myristoylation,
      calcium, and position of the attached dye, while GCAP2 was still able to regulate
      guanylate cyclase in a Ca(2+)-sensitive manner. We observe distinct site-specific
      variations in the fluorescence dynamics when externally changing the protein
      conformation. A clear reduction in fluorescence lifetime suggests that in the
      calcium-free state a dye marker in amino acid position 131 senses a more
      hydrophobic protein environment than in position 111. Saturating GCAP2 with
      calcium increases the fluorescence lifetime and hence leads to larger exposure of
      position 111 to the solvent and at the same time to a movement of position 131
      into a hydrophobic protein cleft. In addition, we find distinct, biexponential
      anisotropy decays reflecting the reorientational motion of the fluorophore dipole
      and the dye/protein complex, respectively. Our experimental data are well
      described by a "wobbling-in-a-cone" model and reveal that for dye markers in
      position 111 of the GCAP2 protein both addition of calcium and myristoylation
      results in a pronounced increase in orientational flexibility of the fluorophore.
      Our results provide evidence that the up-and-down movement of an alpha-helix that
      is situated between position 111 and 131 is a key feature of the dynamics of the
      protein-dye complex. Operation of this piston-like movement is triggered by the
      intracellular messenger calcium.

PMID- 22409624
TI  - Evolution in management of stage I seminoma: the case for patient preference and
      patient/clinician joint internet registration and follow-up study to quantify
      late events.

PMID- 22409625
TI  - Congenital and postnatal factors inducing malocclusions in Japanese unilateral
      cleft lip and palate patients-determination using logistic regression analysis.
AB  - Objective : To assess the congenital and postnatal factors that affect degree of
      malocclusion in patients with unilateral cleft lip and palate using multivariate
      statistical analysis. Design : Retrospective study. Patients : All information on
      135 subjects with unilateral cleft lip and palate was obtained from an oral
      examination and radiograph at the initial examination at an orthodontic clinic
      and from surgical records. Plaster models were taken before orthodontic
      treatment. The ages of the subjects ranged from 5 to 8 years with a mean age of
      6.9 years. All primary surgeries for the patients were performed at a university
      hospital. Main Outcome Measures : The GOSLON Yardstick was used to assess the
      dental arch relationships (degree of malocclusion) in patients. Family history of
      Class III, degree of cleft, and congenitally missing upper lateral incisor on the
      cleft side were chosen as congenital factors inducing malocclusion. Presurgical
      orthopedic treatment, cheiloplasty, and palatoplasty were chosen as postnatal
      factors. Associations between various factors and dental arch relationships were
      assessed using logistic regression analysis. Results : According to adjusted odds
      ratios, family history of Class III is associated with a significantly worse
      dental arch relationship. Palatoplasty using push-back alone correlated to a
      dental arch relationship that was significantly worse than palatoplasty using
      push-back with a buccal flap. Conclusions : Multivariate analysis shows evidence
      that a positive family history of Class III and palatoplasty using push-back
      alone are associated with worse malocclusion of unilateral cleft lip and palate
      patients. 

PMID- 22409626
TI  - Comparison of three-year clinical outcomes with nonextended versus extended dual
      antiplatelet therapy between first- and second-generation drug-eluting stent
      implantation in patients with acute myocardial infarction: data from the infarct
      prognosis study registry.
AB  - BACKGROUND: The difference of the clinical outcomes between nonextended (<=12
      months) and extended (>12 months) dual antiplatelet therapy (DAPT) remains
      unclear in patients with acute myocardial infarction (AMI) implanted by different
      generations of drug-eluting stent (DES). METHODS: We identified 790 consecutive
      patients with AMI who were free from major adverse cardiac events for 12 months
      after first-generation (n = 537) or second-generation DES (n = 253) implantation;
      each DES generation group was further divided into nonextended and extended DAPT.
      RESULTS: During follow-up (median: 40 months), nonextended DAPT in the first
      generation DES group showed a higher rate of cardiac death or MI than was
      observed in the extended DAPT group (14% vs 2%, P < 0.001). However, in the
      second-generation DES group, there was no difference in the occurrence of cardiac
      death and MI between the extended and nonextended groups (4% vs 3%, P = 0.809).
      Nonextended DAPT was the most significant predictor of cardiac death and MI for
      first-generation DES implantation [hazard ratio (HR) = 5.47, 95% confidence
      interval (CI) = 1.53-19.59, P = 0.009] but not for second-generation DES
      implantation [HR = 3.21, 95% CI = 0.21-50.65, P = 0.401]. CONCLUSION: This study
      suggested that the clinical outcomes between nonextended and extended DAPT might
      be different depending on the generation of implanted DESs in patients with AMI.

PMID- 22409628
TI  - Synthesis of bromo-, boryl-, and stannyl-functionalized 1,2
      bis(trimethylsilyl)benzenes via Diels-Alder or C-H activation reactions.
AB  - 1,2-Bis(trimethylsilyl)benzenes are key starting materials for the synthesis of
      benzyne precursors, Lewis acid catalysts, and certain luminophores. We have
      developed efficient, high-yield routes to functionalized 4-R-1,2
      bis(trimethylsilyl)benzenes, starting from either 1,2
      bis(trimethylsilyl)acetylene/5-bromopyran-2-one (2) or 1,2
      bis(trimethylsilyl)benzene (1)/bis(pinacolato)diborane. In the first reaction, 5
      (R = Br) is obtained through a cobalt-catalyzed Diels-Alder cycloaddition. The
      second reaction proceeds via iridium-mediated C-H activation and provides 8 (R =
      Bpin). Besides its use as a Suzuki reagent, compound 8 can be converted into 5
      with CuBr(2) in i-PrOH/MeOH/H(2)O. Lithium-bromine exchange on 5, followed by the
      addition of Me(3)SnCl, gives 10 (R = SnMe(3)), which we have applied for Stille
      coupling reactions. A Pd-catalyzed C-C coupling reaction between 5 and 8 leads to
      the corresponding tetrasilylbiphenyl derivative. The bromo derivative 5 cleanly
      undergoes Suzuki reactions with electron-rich as well as electron-poor
      phenylboronic acids.

PMID- 22409627
TI  - Prieurianin/endosidin 1 is an actin-stabilizing small molecule identified from a
      chemical genetic screen for circadian clock effectors in Arabidopsis thaliana.
AB  - Chemical modulators are powerful tools to investigate biological processes. To
      identify circadian clock effectors, we screened a natural product library in the
      model plant Arabidopsis thaliana. Two compounds, prieurianin (Pri) and
      prieurianin acetate, were identified as causing a shorter circadian period.
      Recently, Pri was independently identified as a vesicle trafficking inhibitor and
      re-named endosidin 1 (ES1). Here we show that Pri primarily affects actin
      filament flexibility in vivo, later resulting in reduced severing and filament
      depolymerization. This stabilization of the actin cytoskeleton subsequently
      causes changes in vesicle trafficking. Pri also affected microfilaments in
      mammalian cells, indicating that its target is highly conserved; however, it did
      not alter actin dynamics in vitro, suggesting that its activity requires the
      presence of actin-associated proteins. Furthermore, well-characterized actin
      inhibitors shortened the period length of the Arabidopsis clock in a similar way
      to Pri, supporting the idea that Pri affects rhythms by altering the actin
      network. We conclude that actin-associated processes influence the circadian
      system in a light-dependent manner, but their disruption does not abolish
      rhythmicity. In summary, we propose that the primary effect of Pri is to
      stabilize the actin cytoskeleton system, thereby affecting endosome trafficking.
      Pri appears to stabilize actin filaments by a different mechanism from previously
      described inhibitors, and will be a useful tool to study actin-related cellular
      processes.

PMID- 22409629
TI  - Discovery of ((S)-5-(methoxymethyl)-7-(1-methyl-1H-indol-2-yl)-2
      (trifluoromethyl)-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl)((S)-2-(3
      methylisoxazol-5-yl)pyrrolidin-1-yl)methanone as a potent and selective I(Kur)
      inhibitor.
AB  - Previously disclosed dihydropyrazolopyrimidines are potent and selective blockers
      of I(Kur) current. A potential liability with this chemotype is the formation of
      a reactive metabolite which demonstrated covalent binding to protein in vitro.
      When substituted at the 2 or 3 position, this template yielded potent I(Kur)
      inhibitors, with selectivity over hERG which did not form reactive metabolites.
      Subsequent optimization for potency and PK properties lead to the discovery of
      ((S)-5-(methoxymethyl)-7-(1-methyl-1H-indol-2-yl)-2-(trifluoromethyl)-4,7
      dihydropyrazolo[1,5-a]pyrimidin-6-yl)((S)-2-(3-methylisoxazol-5-yl)pyrrolidin-1
      yl)methanone (13j), with an acceptable PK profile in preclinical species and
      potent efficacy in the preclinical rabbit atrial effective refractory period
      (AERP) model.

PMID- 22409630
TI  - The one hundred most frequently cited articles in the field of clinical liver
      transplantation.

PMID- 22409631
TI  - Betalain production is possible in anthocyanin-producing plant species given the
      presence of DOPA-dioxygenase and L-DOPA.
AB  - BACKGROUND: Carotenoids and anthocyanins are the predominant non-chlorophyll
      pigments in plants. However, certain families within the order Caryophyllales
      produce another class of pigments, the betalains, instead of anthocyanins. The
      occurrence of betalains and anthocyanins is mutually exclusive. Betalains are
      divided into two classes, the betaxanthins and betacyanins, which produce yellow
      to orange or violet colours, respectively. In this article we show betalain
      production in species that normally produce anthocyanins, through a combination
      of genetic modification and substrate feeding. RESULTS: The biolistic
      introduction of DNA constructs for transient overexpression of two different
      dihydroxyphenylalanine (DOPA) dioxygenases (DODs), and feeding of DOD substrate
      (L-DOPA), was sufficient to induce betalain production in cell cultures of
      Solanum tuberosum (potato) and petals of Antirrhinum majus. HPLC analysis showed
      both betaxanthins and betacyanins were produced. Multi-cell foci with yellow,
      orange and/or red colours occurred, with either a fungal DOD (from Amanita
      muscaria) or a plant DOD (from Portulaca grandiflora), and the yellow/orange foci
      showed green autofluorescence characteristic of betaxanthins. Stably transformed
      Arabidopsis thaliana (arabidopsis) lines containing 35S: AmDOD produced yellow
      colouration in flowers and orange-red colouration in seedlings when fed L-DOPA.
      These tissues also showed green autofluorescence. HPLC analysis of the transgenic
      seedlings fed L-DOPA confirmed betaxanthin production. CONCLUSIONS: The fact that
      the introduction of DOD along with a supply of its substrate (L-DOPA) was
      sufficient to induce betacyanin production reveals the presence of a background
      enzyme, possibly a tyrosinase, that can convert L-DOPA to cyclo-DOPA (or
      dopaxanthin to betacyanin) in at least some anthocyanin-producing plants. The
      plants also demonstrate that betalains can accumulate in anthocyanin-producing
      species. Thus, introduction of a DOD and an enzyme capable of converting tyrosine
      to L-DOPA should be sufficient to confer both betaxanthin and betacyanin
      production to anthocyanin-producing species. The requirement for few novel
      biosynthetic steps may have assisted in the evolution of the betalain
      biosynthetic pathway in the Caryophyllales, and facilitated multiple origins of
      the pathway in this order and in fungi. The stably transformed 35S: AmDOD
      arabidopsis plants provide material to study, for the first time, the
      physiological effects of having both betalains and anthocyanins in the same plant
      tissues.

PMID- 22409632
TI  - ipso-Nitration of arylboronic acids with bismuth nitrate and perdisulfate.
AB  - An efficient and one pot synthetic method of ipso-nitration of arylboronic acids
      has been developed. The high efficiency, general applicability, and broader
      substrate scope including heterocycles and functional groups make this method
      advantageous. Due to its simplicity, we expect to find application of this method
      in synthesis.

PMID- 22409633
TI  - Brain death induced by cerebral haemorrhage - a new porcine model evaluated by CT
      angiography.
AB  - BACKGROUND: Brain death and complications to brain death affects the function of
      organs in the potential donor. Previous animal models of brain death have not
      been able to fully elucidate the mechanisms behind this organ dysfunction, and
      none of the available animal models mimic the most common insult prior to brain
      death: intracerebral haemorrhage. The objective of this study was to develop a
      large animal model of brain death based on a controlled intracerebral haemorrhage
      and verified by computerised tomographic angiography (CTA). METHODS: Twenty pigs
      (range: 26.6-31.2 kg) were randomised to brain death or control. Brain death was
      induced by infusion of blood through a stereotaxically placed needle in the
      internal capsule. Brain death was confirmed by the measured intracranial pressure
      (ICP), lack of corneal and pupillary light reflexes, and atropine test. CTA was
      performed 120-180 min after brain death. The pigs were observed for 8 h after
      brain death. RESULTS: Brain death was declared when the ICP exceeded mean
      arterial pressure after a median of 36 min (range: 28-51 min). Significant
      increases in heart rate, and mean arterial pressure (MAP) were followed by a
      steep decrease. With fluid therapy, the animals demonstrated haemodynamic
      stability. Reflexes disappeared, and atropine did not induce an increase in heart
      rate in the brain dead animals. CTA confirmed loss of cerebral circulation.
      CONCLUSION: This study offers a standardised, clinically relevant porcine model
      of brain death induced by a haemorrhagic attack. Brain death was verified by the
      disappearance of corneal and pupil reflex, atropine test, and CTA.

PMID- 22409634
TI  - A 21-week bone deposition promoting exercise programme increases bone mass in
      young people with Down syndrome.
AB  - AIM: To determine whether the bone mass of young people with Down syndrome may
      increase, following a 21-week conditioning training programme including
      plyometric jumps. METHOD: Twenty-eight participants with Down syndrome (13
      females, 15 males) aged 10 to 19 years were divided into exercise (DS-E; n=14;
      eight females, six males mean age 13y 8mo, SD 2y 6mo) and non-exercise (DS-NE;
      n=14; five females, nine males mean age 15y 5mo, SD 2y 6mo) groups. Total and
      regional (hip and lumbar spine [L1-L4]) bone mineral content (BMC) and total lean
      mass were assessed by dual energy X-ray absorptiometry at baseline and after a 25
      minute training session performed twice a week. Repeated-measures analyses of
      variation were applied to test differences between pre- and posttraining values
      for BMC and total lean mass. Differences between increments were studied with the
      Student's t-test. Linear regression models were fitted to test independent
      relationships. RESULTS: After the intervention, higher increments in total and
      hip BMC, and total lean mass, were observed in the DS-E group (all p<0.05). A
      time * exercise interaction was found for total lean mass (p<0.05). The increment
      in total lean mass, height, and Tanner stage accounted for almost for 60% in the
      increment in total BMC in the DS-NE group (p<0.05). INTERPRETATION: Twenty-one
      weeks of training have a positive effect on the acquisition of bone mass in young
      people with Down syndrome.

PMID- 22409636
TI  - Help across the spectrum: a developmental pediatrician's perspective on
      diagnosing and treating autism spectrum disorders.
AB  - Autism spectrum disorders (ASD), a group of neurodevelopmental disorders
      characterized by marked deficits in social interaction and communication with
      unusually restricted interests, have a tremendous impact on society and are
      increasingly being diagnosed. Increased developmental screening, use of
      standardized diagnostic tests, and a broadening of Diagnostic and Statistical
      Manual of Mental Disorders (American Psychiatric Association, 2000) criteria
      might account for the increased incidence. Evidence-based treatments for children
      with ASD, reviewed by the National Standards Project, are primarily behavioral
      interventions with foundations in the sciences of applied behavior analysis and
      developmental psychology and emphasize improved functional communication and
      social reciprocity.

PMID- 22409635
TI  - Psychosocial factors in adolescent nicotine dependence symptoms: a sample of high
      school juniors who smoke daily.
AB  - Cross-sectionally examined seven theory-guided psychosocial factors associated
      with nicotine dependence symptoms in a representative self-report survey of 794
      Washington State high school junior daily smokers (93% participation). Outcomes
      were four nicotine dependence symptoms. Results showed that low self-efficacy for
      quitting smoking and being around adults who smoke were associated with a 3.48
      10.35 and a 1.47-1.77 times higher odds, respectively, of each of the four
      nicotine dependence symptoms. These results, needing replication in a
      longitudinal study, suggest that interventions designed to enhance self-efficacy
      to quit smoking and counter adult smoking influences might reduce adolescent
      nicotine dependence.

PMID- 22409637
TI  - Disability and employee benefits receipt: evidence from the U.S. Vocational
      Rehabilitation Services Program.
AB  - Studies indicate positive effects of the U.S. Vocational Rehabilitation Services
      (VRS) in assisting people with disabilities to find independent employment.
      Underemployment continues to impact access to adequate health care and other
      benefits. Workers with disabilities receive fewer benefits, overall. With data
      from the Longitudinal Study of Vocational Rehabilitation Services Program
      (LSVRSP), the authors compare the rates of receipt of 6 types of benefits for
      people with physical, mental, and sensory impairments. Although those with
      physical disabilities are most likely to receive benefits, all groups lack
      adequate access to health care, sick leave, and vacation. The authors discuss
      implications for services provision in the current job market.

PMID- 22409638
TI  - Mental health status of the Hmong Americans in 2011: three decades revisited.
AB  - This article provides a comprehensive overview of the Hmong in America and
      encompasses their mental health status for the past 35 years. Since their mass
      arrival to the United States in 1975, limited research has been compiled to track
      the specific mental health issues that affect this collective community alone.
      Major chronological research findings were compiled for this article and specific
      findings concerning the Hmong and their mental health issues were compared to
      findings for other Southeast Asian groups. In conclusion, the findings of this
      article indicate that the Hmong still have higher rates of being diagnosed with
      depression, the lowest help-seeking behaviors in utilizing Western medicine, and
      the lowest arithmetic average of "happiness" scaled on an assessment tool. The
      purpose of this article is to better steer future research projects that entail
      tracking and differentiating the specific mental health domains of the Hmong.

PMID- 22409639
TI  - A community-based organization: the Las Mercedes Project.
AB  - Using the Las Mercedes Project as an example, the aim of this article is to
      discuss the philosophy and practice of community-based projects. At the core of
      such projects is a shift in understanding the nature of community. A community,
      in this case, represents a reality that persons construct that determines the
      character of rules, norms, and the focus and style of interventions.
      Additionally, community-based organizations, such as the Las Mercedes Project,
      are fully participatory, decentered, and carry the imprint of a community's
      members. Community-based projects, in this regard, improve the likelihood of
      creating successful interventions.

PMID- 22409640
TI  - Adhesion of polyelectrolyte multilayers: sealing and transfer of microchamber
      arrays.
AB  - Polyelectrolyte multilayer (PEM) films with array of responsive microchambers are
      promising candidates for site-specific release of chemicals in small and
      precisely defined quantities on demand. It requires effective sealing of the
      microchambers toward a support to prevent leakage of a cargo. In this paper, we
      study the pressure-induced adhesion of poly(allylammonium)-poly(4
      styrenesulfonate) (PAH-PSS) multilayers assembled on different templates toward
      the poly(4-styrenesulfonate)-poly(diallyldimethylammonium) multilayer. The
      tensile bond strength increases from 0.4 to 3.5 MPa upon the increase of PAH-PSS
      bilayers from 10 to 40, if assembled on a silicon template. Weaker tensile bond
      strength of 0.35 MPa between the PAH-PSS multilayer and a
      poly(methylmethacrylate) (PMMA) template results in adhesive break at this
      interface and allows mechanical removal of the template. The successful PEM
      transfer is demonstrated for templates of various geometrical patterns, while the
      tensile break of a multilayer film happens for the others.

PMID- 22409642
TI  - Postdeployment Battlemind training for the U.K. armed forces: a cluster
      randomized controlled trial.
AB  - OBJECTIVE: Combat exposure can increase the risk of subsequent psychological ill
      health in armed forces (AF) personnel. A U.S. postdeployment psycho-educational
      intervention, Battlemind, showed a beneficial effect on mental health in U.S.
      military personnel exposed to high combat levels. We evaluated the effectiveness
      of an anglicized version of postdeployment Battlemind. METHOD: Battlemind was
      adapted for the United Kingdom. The main amendments were to sections about
      carrying weapons, driving, and alcohol misuse. The anglicized Battlemind was
      compared with the U.K. standard postdeployment brief in a cluster randomized
      controlled trial. At baseline, 2,443 U.K. AF personnel returning from Afghanistan
      via Cyprus completed questionnaires about their combat experiences and mental
      health. Of these, 1,616 (66%) completed 6-month follow-up questionnaires. We used
      the Posttraumatic Stress Disorder Checklist (PCL-C) to measure probable
      posttraumatic stress disorder and the General Health Questionnaire (GHQ-12) to
      measure common mental disorders. Secondary outcomes included alcohol misuse,
      assessed with the Alcohol Use Disorders Identification Test (AUDIT), and binge
      drinking. Mixed-effects models were used to account for possible cluster effects.
      RESULTS: We did not find a difference in mental health or overall AUDIT score.
      Those who received Battlemind versus the standard brief were less likely to
      report binge drinking, although the effect size was small (adjusted odds ratio =
      0.73, 95% CI [0.58, 0.92]). CONCLUSIONS: The anglicized Battlemind did not
      improve mental health but had a modest impact on the reporting of binge drinking.
      Alcohol misuse is problematic in military populations; therefore, an intervention
      that reduces binge drinking may be helpful.

PMID- 22409641
TI  - Treatment-specific changes in decentering following mindfulness-based cognitive
      therapy versus antidepressant medication or placebo for prevention of depressive
      relapse.
AB  - OBJECTIVE: To examine whether metacognitive psychological skills, acquired in
      mindfulness-based cognitive therapy (MBCT), are also present in patients
      receiving medication treatments for prevention of depressive relapse and whether
      these skills mediate MBCT's effectiveness. METHOD: This study, embedded within a
      randomized efficacy trial of MBCT, was the first to examine changes in
      mindfulness and decentering during 6-8 months of antidepressant treatment and
      then during an 18-month maintenance phase in which patients discontinued
      medication and received MBCT, continued on antidepressants, or were switched to a
      placebo. In total, 84 patients (mean age = 44 years, 58% female) were randomized
      to 1 of these 3 prevention conditions. In addition to symptom variables, changes
      in mindfulness, rumination, and decentering were assessed during the phases of
      the study. RESULTS: Pharmacological treatment of acute depression was associated
      with reductions in scores for rumination and increased wider experiences. During
      the maintenance phase, only patients receiving MBCT showed significant increases
      in the ability to monitor and observe thoughts and feelings as measured by the
      Wider Experiences (p < .01) and Decentering (p < .01) subscales of the
      Experiences Questionnaire and by the Toronto Mindfulness Scale. In addition,
      changes in Wider Experiences (p < .05) and Curiosity (p < .01) predicted lower
      Hamilton Rating Scale for Depression scores at 6-month follow-up. CONCLUSIONS: An
      increased capacity for decentering and curiosity may be fostered during MBCT and
      may underlie its effectiveness. With practice, patients can learn to counter
      habitual avoidance tendencies and to regulate dysphoric affect in ways that
      support recovery.

PMID- 22409643
TI  - Anxiety and depression in breast cancer survivors of different sexual
      orientations.
AB  - OBJECTIVE: We conducted a study comparing anxiety and depression by sexual
      orientation in long-term breast cancer survivors, testing the hypothesis that
      sexual minority women (e.g., lesbian and bisexual women) have greater levels of
      anxiety and depression. METHOD: From a state cancer registry, we recruited 257
      heterosexual and 69 sexual minority women with a diagnosis of primary,
      nonmetastatic breast cancer. To increase the number of sexual minority
      participants, we used convenience recruitment methods and obtained an additional
      112 sexual minority women who fit the same eligibility criteria as did the
      registry-derived sample. Using a telephone survey, we assessed clinical and
      demographic characteristics of the participants and the outcomes of anxiety and
      depression using the Hospital Anxiety and Depression Scale (Zigmond & Snaith,
      1983). RESULTS: We did not confirm our study hypothesis but found that sexual
      orientation is associated with anxiety and depression through interactions with
      demographic and clinical factors. Younger age and lower socioeconomic status are
      associated with worse anxiety and depression. These factors explain less than 20%
      of the variance in anxiety and depression. CONCLUSIONS: This sample of long-term
      breast cancer survivors shows low levels of psychological morbidity, while some
      sexual minority survivors are more depressed. Future research should examine
      explanatory factors to account for the better-than-expected psychological
      rehabilitation of sexual minority survivors.

PMID- 22409644
TI  - Predictors of treatment response to cognitive-behavioral therapy for depression
      in Parkinson's disease.
AB  - OBJECTIVE: The purpose of this study was to examine predictors of treatment
      response to cognitive-behavioral therapy (CBT) for depression in Parkinson's
      disease (PD). METHOD: The sample comprised 80 depressed (DSM-IV criteria) adults
      with PD (60% male) and their caregivers who participated in an National
      Institutes of Health-sponsored randomized-controlled trial of CBT vs. clinical
      monitoring from April 2007 until July 2010. Individually administered CBT was
      provided to people with PD for 10 weeks, modified to address the unique needs of
      the medical population, and supplemented with up to 4 separate caregiver
      educational sessions. Treatment response was defined a priori as a rating of
      depression much improved or very much improved on the Clinical Global Impression
      Improvement Scale or >= 50% reduction in the baseline Hamilton Depression Rating
      Scale score. It was hypothesized (a priori) that caregiver participation in
      treatment, motor disability, psychiatric comorbidity, and executive functioning
      would be significant predictors of response to CBT at end-of-treatment (Week 10)
      and short-term follow-up (Week 14). RESULTS: At Week 10, caregiver participation
      was the only significant predictor of treatment response in the CBT group. At
      Week 14, both caregiver participation and executive functioning predicted
      response to CBT. Treatment group, baseline depression severity, executive
      functioning, motor disability, psychiatric comorbidity, marital status, and
      caregiver burden were also related to change in depression scores, for all
      participants, in secondary and exploratory models. CONCLUSIONS: Caregiver
      participation may enhance acute treatment response to psychosocial interventions
      for depression in PD. Further research is needed to extend and replicate these
      findings.

PMID- 22409645
TI  - Quantitative computer-based assessment of lip symmetry following cleft lip
      repair.
AB  - Objective : To demonstrate an objective method of measuring lip symmetry after
      cleft lip repair by comparing patients with unilateral cleft lip (UCL) to non
      cleft lip controls using the SymNose computer program. Design : Retrospective
      cohort study comparing several parameters of lip symmetry between UCL cases and
      controls. Participants were represented by digital photographs that were traced
      using SymNose. Setting : This study was performed at the South West Cleft Unit,
      Bristol, U.K. Participants : Forty-four participants aged 10 years (+/-1 year)
      were recruited into and completed the study. A consecutive case series of 22
      patients with UCL +/- palate had previously undergone primary repair. Twenty-two
      age-matched controls were recruited from a local primary school. Main Outcome
      Measures : Lip symmetry, expressed as the percentage mismatch of an overlaying of
      the left upper lip area and upper vermillion border area over the right,
      horizontal lip tilt, and lateral deviation of the lips. Results : A significant
      increase in labial asymmetry was seen in the UCL group in the following
      parameters: upper lip mismatch and upper vermillion border mismatch. No
      significant differences were observed in horizontal lip tilt or lateral lip
      deviation. Conclusion : This study supports the use of SymNose for the objective
      quantitative assessment of lip symmetry as an outcome measure of surgery
      following cleft lip repair. It allows comparison of surgical techniques and can
      be used to perform audits. It is a time-efficient process, relatively
      inexpensive, and straightforward to use.

PMID- 22409646
TI  - Cloning and characterization of SOC1 homologs in barley (Hordeum vulgare) and
      their expression during seed development and in response to vernalization.
AB  - A number of genes are involved in the vernalization pathway, such as VRN1, VRN2
      and VRN3/FT1, whose function has been studied in barley and wheat. However, the
      function of the flowering and vernalization integrator SUPPRESSOR OF
      OVEREXPRESSION OF CONSTANS 1 (SOC1) has not been well studied in Triticeae, and
      particularly in barley. Herein, we cloned and characterized two barley SOC1-like
      homologs, HvSOC1-like1 and HvSOC1-like2. Primary sequence analysis of the
      predicted HvSOC1-like1 and HvSOC1-like2 proteins showed that they are members of
      the type II MADS-box protein family. Phylogenetic analysis placed the predicted
      proteins with other SOC1 and SOC1-like proteins from different species
      neighboring those from other cereal plant species. Primary and secondary
      structures of the predicted proteins are conserved to each other and more distant
      to the recently identified barley ODDSOC1 proteins. Genomic organization of
      HvSOC1-like1 is very similar to the Arabidopsis and Brachypodium SOC1 genes and
      localized in highly syntenic chromosomal regions. Regulatory cis-acting elements
      detected in the HvSOC1-like1 promoter include the CArG-box, implicated in the
      regulation of SOC1 expression in Arabidopsis. Both HvSOC1-like1 and HvSOCI-like2
      are expressed in vegetative and reproductive tissues and at different stages of
      seed development. Both are upregulated in a particular seed developmental stage
      suggesting their possible implication in seed development. Furthermore, HvSOC1
      like1 was induced in two winter barley cultivars after vernalization treatment
      pointing to its probable involvement in the vernalization process. The study of
      the SOC1 genes reported here opens the way for a better understanding of both the
      vernalization process and seed development and germination in this important
      cereal crop.

PMID- 22409647
TI  - Detection, characterization, and screening of heme-binding molecules by mass
      spectrometry for malaria drug discovery.
AB  - Drug screening for antimalarials uses heme biocrystallization inhibition methods
      as an alternative to parasite cultures, but they involve complex processes and
      cannot detect artemisinin-like molecules. The described method detects heme
      binding compounds by mass spectrometry, using dissociation of the drug-heme
      adducts to evaluate putative antiplasmodial activity. Applied to a chemical
      library, it showed a good hit-to-lead ratio and is an efficient early stage
      screening for complex mixtures like natural extracts.

PMID- 22409648
TI  - Antifungal prophylaxis in haematology patients: the role of voriconazole.
AB  - Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in
      haematopoietic stem cell transplant (HCT) recipients and patients with
      haematological malignancies. Early treatment initiation is vital for improving
      survival, but is hampered by difficulties in timely diagnosis. Prophylaxis with a
      broad-spectrum antifungal, such as voriconazole, has the potential to decrease
      the incidence of IFI in haematology patients. Based on a growing body of data,
      voriconazole appears to be effective for the primary and secondary prevention of
      IFIs in HCT recipients, with generally good tolerability.

PMID- 22409649
TI  - Management of vaginal dryness and dyspareunia in estrogen sensitive cancer
      patients.
AB  - Cancer patients suffer from vaginal dryness and dyspareunia earlier and longer
      than the general population, with more severe and distressing symptoms. Life
      style advices are the first step and vaginal lubricants can be tried, but they
      can't completely relieve atrophic symptoms. The most effective therapy is use of
      vaginal estrogens, but compliance and management are particularly difficult in
      estrogen sensitive cancer patients because of their systemic absorption.
      Compliance can be improved if they are begun at a very low dose and gradually
      increased until the lowest effective dose is reached. Promestriene only possesses
      an intramucosal effect, it can be used at very low doses in cancer patients
      suffering from urogenital symptoms.

PMID- 22409650
TI  - Modelling coordination in hospital emergency departments through social network
      analysis.
AB  - Coordination theory provides a theoretical framework for analysing complex
      processes of project groups working towards a common goal. In this study, we
      explore the relationship between coordination and social networks for the
      development of a network-based coordination model. This model is applied to
      measure the performance and quality of complex and dynamic project coordination
      such as in hospital emergency departments. The dataset used for the study was
      collected by the 2004 National Hospital Ambulatory Medical Care Survey--a
      national probability sample survey of visits to emergency and outpatient
      departments of non-Federal, short-stay and general hospitals in the United
      States. Using social network analysis, this study allows us to understand the
      possible causes of inefficient coordination performance and coordination quality
      resulting in access blocks.

PMID- 22409652
TI  - Nasopalatine Duct Cyst, a delayed complication to successful dental implant
      placement: Diagnosis and surgical management.
AB  - Abstract   The dental literature reports frequently on both the success and
      survival of dental implants whereby the focus remains on the hard and soft tissue
      biological response to the implants. The predication and anticipation of adverse
      implant events can then lead to the pre-emption of implant loss. However,
      biological situations can arise that are outside the control of the clinician.
      The author reports a case history of the late manifestation of a Nasopalatine
      Duct Cyst (NPDC) in close proximity to a dental implant and its subsequent
      surgical management.

PMID- 22409651
TI  - Modified vocal function exercises: a case report.
AB  - OBJECTIVES: The aim of this case report is to highlight the modifications made to
      vocal function exercises to suit patient's ability. Study design. Single case
      report-retrospective. METHODS: This case study is about a 77-year-old female with
      vocal fold atrophy who had difficulty demonstrating the vocal function exercises
      regimen. Voice therapy techniques were modified for this patient. RESULTS: Post
      therapy examination showed significant improvement in perceptual, objective, and
      self-perceptual analysis of voice. CONCLUSION: The modified version can be an
      option for those patients unable to follow the instructions of vocal function
      exercises.

PMID- 22409653
TI  - Pyridine ligands as promoters in Pd(II/0)-catalyzed C-H olefination reactions.
AB  - Commercially available pyridine ligands can significantly enhance the rate,
      yield, substrate scope, and site selectivity of arene C-H olefination (Fujiwara
      Moritani) reactions. The use of a 1:1 ratio of Pd/pyridine proved critical to
      maximize reaction rates and yields.

PMID- 22409655
TI  - Ultraslow dynamics at crystallization of a room-temperature ionic liquid, 1-butyl
      3-methylimidazolium bromide.
AB  - We studied the crystallization process of 1-butyl-3-methylimidazolium bromide
      ([C(4)mim]Br) using measurements of supersensitive scanning calorimetry, free
      induction decay (FID) signals of (1)H NMR, and direct observation. These three
      methods provided consistent, complementary results, which showed extremely slow
      dynamics at crystallization. This sample does not crystallize during the cooling
      process, loses mobility, and changes to a coagulated state, which is not the
      thermodynamic glass state. The FID signals and direct observation in the heating
      process indicate that the coagulated sample liquefies just before
      crystallization. The crystallization of [C(4)mim]Br does not occur from
      specialized locations such as the surface or wall of the sample tube but randomly
      in the liquid. The calorimetric measurements show that it takes 150 min for
      approximately 3 mg of this sample to crystallize perfectly. Conformational
      changes of the butyl group continue for approximately 330 min after
      crystallization. Such slow dynamics are thought to be due to the cooperative
      linking of crystallization and complex conformational changes in dense fields
      with high viscosity.

PMID- 22409654
TI  - Phytochrome-imposed oscillations in PIF3 protein abundance regulate hypocotyl
      growth under diurnal light/dark conditions in Arabidopsis.
AB  - Arabidopsis seedlings display rhythmic growth when grown under diurnal
      conditions, with maximal elongation rates occurring at the end of the night under
      short-day photoperiods. Current evidence indicates that this behavior involves
      the action of the growth-promoting bHLH factors PHYTOCHROME-INTERACTING FACTOR 4
      (PIF4) and PHYTOCHROME-INTERACTING FACTOR 5 (PIF5) at the end of the night,
      through a coincidence mechanism that combines their transcriptional regulation by
      the circadian clock with control of protein accumulation by light. To assess the
      possible role of PIF3 in this process, we have analyzed hypocotyl responses and
      marker gene expression in pif single- and higher-order mutants. The data show
      that PIF3 plays a prominent role as a promoter of seedling growth under diurnal
      light/dark conditions, in conjunction with PIF4 and PIF5. In addition, we provide
      evidence that PIF3 functions in this process through its intrinsic
      transcriptional regulatory activity, at least in part by directly targeting
      growth-related genes, and independently of its ability to regulate phytochrome B
      (phyB) levels. Furthermore, in sharp contrast to PIF4 and PIF5, our data show
      that the PIF3 gene is not subject to transcriptional regulation by the clock, but
      that PIF3 protein abundance oscillates under diurnal conditions as a result of a
      progressive decline in PIF3 protein degradation mediated by photoactivated phyB,
      and consequent accumulation of the bHLH factor during the dark period.
      Collectively, the data suggest that phyB-mediated, post-translational regulation
      allows PIF3 accumulation to peak just before dawn, at which time it accelerates
      hypocotyl growth, together with PIF4 and PIF5, by directly regulating the
      induction of growth-related genes.

PMID- 22409656
TI  - Beneficial effects of transcatheter closure of atrial septal defects not only in
      young adults.
AB  - OBJECTIVES: To compare cardiac events and remodeling effects after transcatheter
      closure of atrial septal defects (ASD) in pediatric, adult, and older adult
      patients. METHODS: A retrospective review was conducted of 353 patients who
      underwent transcatheter ASD closure between February 1999 and December 2007 at
      Siriraj Hospital. The patients were divided into 3 groups according to age:
      children (<18 years; n = 99); adults (18-50 years; n = 169); and older adults
      (>50 years; n = 85). Cardiac events at 1 year, and changes in left and right
      ventricular dimensions between preprocedure and 6 months and 1 year postprocedure
      were compared between groups. RESULTS: Of the 353 patients, the average size of
      ASD was 22.1 +/- 6.6 mm. Device: ASD diameter was 1.25 +/- 0.28 mm. At 1 year
      postprocedure, the prevalence of chest discomfort and atrial fibrillation (AF)
      was higher in older adult patients, compared to the other age groups. Device
      embolization, cardiac erosion, pericardial effusion, syncope, migraine, thrombus
      formation, and residual shunt did not differ between groups. Within the first 6
      months, the right ventricular (RV) dimension tended to dramatically decrease,
      while the left ventricular (LV) dimension increased in all age groups. These
      changes leveled off in children and in older adults, but in the adult group (18
      50 years), RV shrinkage and LV expansion continued for 1 year. A low rate of
      early and late complications was noted. CONCLUSION: Transcather closure of ASD
      can cause cardiac remodeling, regardless of the patient's age at the time of the
      procedure. For older adult patients, the long-term risk of AF continuation and
      chest discomfort is likely.

PMID- 22409657
TI  - Selective two-step oxidation of MU2-S ligands in trigonal prismatic unit {Re3(MU6
      C)(MU2-S)3Re3} of the bioctahedral cluster anion [Re12CS17(CN)6]6-.
AB  - An oxidation of cluster anion [Re(12)CS(17)(CN)(6)](6-) by H(2)O(2) in water has
      been investigated. It was shown that selective two-step oxidation of bridging
      MU(2)-S-ligands in trigonal prismatic unit {Re(3)(MU(6)-C)(MU(2)-S)(3)Re(3)}
      takes place. The first stage runs rapidly, whereas the speed of the second stage
      depends on intensity of ultraviolet irradiation of the reaction mixture. Each
      stage of the reaction is accompanied by a change in the solution's color. In the
      first stage of the oxidation, the cluster anion [Re(12)CS(14)(SO(2))(3)(CN)(6)](6
      ) is produced, in which all bridging S-ligands are turned into bridging SO(2)
      ligands. The second stage of the oxidation leads to formation of the anion
      [Re(12)CS(14)(SO(2))(2)(SO(3))(CN)(6)](6-), in which one of the SO(2)-ligands
      underwent further oxidation forming the bridging SO(3)-ligand. Seven compounds
      containing these anions were synthesized and characterized by a set of different
      methods, elemental analyses, IR and UV/vis spectroscopy, and quantum-chemical
      calculations. Structures of some compounds based on similar cluster anions,
      [Cu(NH(3))(5)](3)[Re(12)CS(14)(SO(2))(3)(CN)(6)].9.5H(2)O,
      [Ni(NH(3))(6)](3)[Re(12)CS(14)(SO(2))(3)(CN)(6)].4H(2)O, and
      [Cu(NH(3))(5)](2.6)[Re(12)CS(14)(SO(2))(3)(CN)(6)](0.6)[{Re(12)CS(14)(SO(2))(2)(S
      (3))(CN)(5)(MU-CN)}{Cu(NH(3))(4)}](0.4).5H(2)O, were investigated by X-ray
      analysis of single crystals.

PMID- 22409658
TI  - Rituximab therapy prevents focal and segmental glomerulosclerosis recurrence
      after a second renal transplantation.
AB  - Preventive treatment of focal and segmental glomerulosclerosis (FSGS) allograft
      recurrence in high risk recipients having a prior history of graft loss caused by
      FSGS recurrence is still a challenging question. We retrospectively identified
      four patients who underwent a second renal transplantation because of recurrent
      FSGS and who received Rituximab therapy as a prophylactic treatment. Loss of
      their first allograft was directly related to an early (<3 months) recurrence of
      FSGS that was either resistant to plasmapheresis therapy in two cases or had
      escaped to this therapeutic management in the two others. After the second renal
      transplantation, all patients were free of FSGS recurrence during follow-ups that
      were between 12 and 54 months long. These preliminary results demonstrate for the
      first time that Rituximab therapy may constitute an attractive prophylactic
      option for patients being considered for a second renal transplantation because
      of recurrent FSGS in their first graft.

PMID- 22409659
TI  - Correlations between prescription of anti-hypertensive medication and mortality
      due to stroke.
AB  - BACKGROUND: One of the most important risk factors for stroke is hypertension. A
      number of studies have attempted to identify the most effective anti-hypertensive
      therapeutic group for stroke prevention. Using an epidemiologic approach we aimed
      to find correlations based on Hungarian data on stroke-mortality and on
      prescription routine of anti-hypertensive therapeutics in three different
      counties, showing significant difference in stroke mortality. METHODS: We have
      used the official yearly reports on stroke-mortality for the period 2003-2008.
      Based on the significant differences in the change in mortality due to stroke
      three counties were selected: Baranya, Bekes and Hajdu-Bihar. The usage of
      antihypertensive therapeutic groups was analyzed. The correlation of stroke
      mortality difference and different antihypertensive treatment habits was analyzed
      by using normality test, time series analyses, correlation coefficient, paired
      samples test, one sample test and chi-square test. RESULTS: For the year 2003
      stroke-mortality standardized with the county population number was highest in
      county Bekes, followed by county Baranya and county Hajdu-Bihar. For each year
      stroke mortality has shown significant (p < 0.0001) difference between the three
      counties and the ranking/order of the counties has been preserved over time.
      During the period of our study, an increase in the number of days of treatment
      was observed for most of the anti-hypertensive drugs listed. We have observed
      that the increased use of high-ceiling diuretics resulted in a mortality
      advantage, and the reduction in use of calcium channel blockers with direct
      cardiac effect had negative consequences. CONCLUSIONS: The authors acknowledge
      that by limiting the study to three counties the findings cannot be generalized
      to the whole Hungarian population. Two trends can still be identified:i)
      increased number of days of treatment (and therefore the probable use) of high
      ceiling diuretics is associated with reduction in mortality due to stroke and its
      immediate complications; ii) reduction in the use of non-dihidropiridin CCBs does
      not seem justified, as their use appears to be advantageous in stroke prevention.
      Authors put emphasis on the importance of the adherence of the patients to the
      preventive therapies. Health care professionals could provide an important added
      value to the life long preventive therapies by improving the compliance of their
      patients, giving personalized care and advice.

PMID- 22409660
TI  - Globalization of surgical expertise without losing the human touch: utilising the
      network, old and new.

PMID- 22409661
TI  - Pyruvate dehydrogenase deficiency and the brain.

PMID- 22409662
TI  - Stability and change in markers of core numerical competencies.
AB  - Dot enumeration (DE) and number comparison (NC) abilities are considered markers
      of core number competence. Differences in DE/NC reaction time (RT) signatures are
      thought to distinguish between typical and atypical number development. Whether a
      child's DE and NC signatures change or remain stable over time, relative to other
      developmental signatures, is unknown. To investigate these issues, the DE and NC
      RT signatures of 159 children were assessed 7 times over 6 years. Cluster
      analyses identified within-task and across-age subgroups. DE signatures comprised
      4 parameters: (a) the RT slope within the subitizing range, (b) the RT slope for
      the counting range, (c) the subitizing range (indicated by the point of slope
      discontinuity), and (d) the overall average DE RT response. NC RT signatures
      comprised 2 parameters (NC intercept and slope) derived from RTs comparing
      numbers 1 to 9. Analyses yielded 3 distinct DE and NC profiles at each age.
      Within-age subgroup profiles reflected differences in 3 of the 4 DE parameters
      and only 1 NC parameter. Systematic changes in parameters were observed across
      ages for both tasks, and both tasks broadly identified the same subgroups. Sixty
      nine percent of children were assigned to the same subgroup across age, even
      though parameters themselves changed across age. Subgroups did not differ in
      processing speed or nonverbal reasoning, suggesting that DE and NC do not tap
      general cognitive abilities but reflect individual differences specific to the
      domain of numbers. Indeed, both DE and NC subgroup membership at 6 years
      predicted computation ability at 6 years, 9.5 years, and 10 years.

PMID- 22409663
TI  - Mere exposure revisited: the influence of growth versus security cues on
      evaluations of novel and familiar stimuli.
AB  - Combining regulatory focus theory (Higgins, 1997) and novelty categorization
      theory (Forster, Marguc, & Gillebaart, 2010), we predicted that novel stimuli
      would be more positively evaluated when focused on growth as compared with
      security and that familiar stimuli would be more negatively evaluated when
      focused on growth as compared with security. This would occur, at least in part,
      because of changes in category breadth. We tested effects of several variables
      linked to growth and security on evaluations of novel and familiar stimuli. Using
      a subliminal mere exposure paradigm, results showed novel stimuli were evaluated
      more positively in a promotion focus compared to a prevention focus (Experiments
      1A-1C), with high power compared to low power (Experiment 2A), and with the color
      blue compared to red (Experiment 2B). For familiar stimuli, all effects were
      reversed. Additionally, as predicted by novelty categorization theory, novel
      stimuli were liked better after broad compared to narrow category priming, and
      familiar stimuli were liked better after narrow compared with broad category
      priming (Experiment 3). We suggest, therefore, that although familiarity glows
      warmly in security-related contexts, people prefer novelty when they are
      primarily focused on growth.

PMID- 22409664
TI  - The pot calling the kettle black: distancing response to ethical dissonance.
AB  - Six studies demonstrate the "pot calling the kettle black" phenomenon whereby
      people are guilty of the very fault they identify in others. Recalling an
      undeniable ethical failure, people experience ethical dissonance between their
      moral values and their behavioral misconduct. Our findings indicate that to
      reduce ethical dissonance, individuals use a double-distancing mechanism. Using
      an overcompensating ethical code, they judge others more harshly and present
      themselves as more virtuous and ethical (Studies 1, 2, 3). We show this mechanism
      is exclusive for ethical dissonance and is not triggered by salience of
      ethicality (Study 4), general sense of personal failure, or ethically neutral
      cognitive dissonance (Study 5). Finally, it is characterized by some boundary
      conditions (Study 6). We discuss the theoretical contribution of this work to
      research on moral regulation and ethical behavior.

PMID- 22409665
TI  - Does positive affect broaden and negative affect narrow attentional scope? A new
      answer to an old question.
AB  - The current research challenges the common view that positive affect and negative
      affect generate a broadened or narrowed attentional focus, respectively. Contrary
      to this view, two studies found that the link between affect and attentional
      focus as measured by a traditional flanker task (Study 1) and a modified flanker
      task (Study 2) reflects whatever focus is momentarily dominant. Further, in these
      studies when neither focus was dominant, the link between affect and attentional
      focus vanished. These results demonstrate that, like reward, positive affect and
      negative affect are not dedicated to a particular broadened or narrowed
      attentional scope but rather provide embodied information about the value of
      currently accessible attentional orientations.

PMID- 22409666
TI  - Modern phenotypic drug discovery is a viable, neoclassic pharma strategy.

PMID- 22409667
TI  - Mental health problems, legal involvement, and smoking during pregnancy.
AB  - The current study examined predictors of past 30-day cigarette use among a US
      nationally representative sample of pregnant women over the age of 18 (N =
      1,782). The study consisted of secondary data analysis of the 2005-2007 survey
      years of the National Survey on Drug Use and Health (NSDUH). Logistic regression
      analyses indicated that low-income women, those who experienced mental health
      problems in the past year, and women who experienced legal problems were more
      likely to smoke during pregnancy. Limitations to the study as well as
      implications for future research are discussed.

PMID- 22409668
TI  - Silica encapsulation by miniemulsion polymerization: distribution and
      localization of the silica particles in droplets and latex particles.
AB  - The impact of including hydrophobically modified silica on the morphology of
      miniemulsified monomer mixtures and that of the resulting polymer particles was
      investigated, with emphasis placed on the distribution and localization of the
      inorganic phase. Silica nanoparticles with diameters of 20 and 78 nm were first
      modified with gamma-methacryloxypropyl trimethoxysilane (gamma-MPS) to favor
      their dispersion in methyl methacrylate (MMA)/n-butyl acrylate (BuA) and mixtures
      of varying MMA to BuA weight ratios. The monomer-silica dispersions were then
      emulsified by ultrasonication, and the resulting silica-loaded droplets were
      examined using cryo-transmission electron microscopy (cryo-TEM). This represents
      the first time such silica-loaded nanodroplets were examined in this way. The
      results of the cryo-TEM show that whereas the silica particles could easily be
      dispersed in MMA or a mixture of MMA and BuA to produce stable dispersions, the
      emulsification step promotes the (re)localization of the silica at the oil-water
      interfaces. It was also shown that not all droplets are equal; some droplets and
      particles contain no silica whereas others contain many silica particles. After
      the subsequent polymerization step, the silica was buried inside the latex
      particles.

PMID- 22409669
TI  - Quantum dot (QD)-modified carbon tape electrodes for reproducible
      electrochemiluminescence (ECL) emission on a paper-based platform.
AB  - Stable and sensitive electrochemiluminescence (ECL) detection relies on
      successful immobilization of quantum dots (QDs) on working electrodes. Herein, we
      report a new technique to apply double-sided carbon adhesive tape as the working
      electrode to improve the stability and reproducibility of QD-based ECL emission.
      CdS QD-modified electrodes were prepared by dropping and drying CdS QD suspension
      on the carbon adhesive tape supported by indium tin oxide (ITO) glass. The ECL
      detection was performed with the prepared electrode on a paper-based platform. We
      tested our system using H(2)O(2) of various concentrations and demonstrated that
      consistent ECL emission could be obtained. We attribute stable and reproducible
      ECL emission to the robust attachment of CdS QDs on the carbon adhesive tape. The
      proposed method could be used to quantify the concentration of dopamine from 1
      MUM to 10 mM based on the quenching effect of dopamine on ECL emission of CdS QD
      system using H(2)O(2) as the coreactant. Our approach addressed the problem in
      the integration of stable QD-based ECL detection with portable paper-based
      analytical devices. The similar design offers great potential for low-cost
      electrochemical and ECL analytical instruments.

PMID- 22409670
TI  - Understanding plant cold hardiness: an opinion.
AB  - How plants adapt to freezing temperatures and acclimate to survive the formation
      of ice within their tissues has been a subject of study for botanists and plant
      scientists since the latter part of the 19th century. In recent years, there has
      been an explosion of information on this topic and molecular biology has provided
      new and exciting opportunities to better understand the genes involved in cold
      adaptation, freezing response and environmental stress in general. Despite an
      exponential increase in our understanding of freezing tolerance, understanding
      cold hardiness in a manner that allows one to actually improve this trait in
      economically important crops has proved to be an elusive goal. This is partly
      because of the growing recognition of the complexity of cold adaptation. The
      ability of plants to adapt to and survive freezing temperatures has many facets,
      which are often species specific, and are the result of the response to many
      environmental cues, rather than just low temperature. This is perhaps
      underappreciated in the design of many controlled environment experiments
      resulting in data that reflects the response to the experimental conditions but
      may not reflect actual mechanisms of cold hardiness in the field. The information
      and opinions presented in this report are an attempt to illustrate the many
      facets of cold hardiness, emphasize the importance of context in conducting cold
      hardiness research, and pose, in our view, a few of the critical questions that
      still need to be addressed.

PMID- 22409671
TI  - Don't leave regulation to its own devices.

PMID- 22409672
TI  - Device regulation: what next?

PMID- 22409673
TI  - Coming out: is the Mardi Gras still needed?

PMID- 22409674
TI  - Tertiary education institutions should not offer pseudoscientific medical
      courses.

PMID- 22409675
TI  - Time to debate one-click transparency.

PMID- 22409676
TI  - Transforming Australia's Breast Implant Registry.

PMID- 22409677
TI  - Private specialist practice: the forgotten sector in health care reform.

PMID- 22409678
TI  - Diamantina Health Partners: integrating leadership in research, research
      translation, education and clinical care.
AB  - Many have asked "what is the benefit of the DHP over the current situation?" We
      believe that the responsiveness of research to community health needs and the
      balance of research and teaching outcomes in academic institutions can be
      improved, and stronger incentives to integrate research outcomes into clinical
      practice can be provided. The DHP is thus set up differently to a clinical
      research centre. The aim of our DHP is to improve health outcomes by means of
      coordinated excellence in teaching, research and clinical care. Technical
      efficiencies and excellence in care mean that financial efficiencies will occur.
      Joint clinical, research and teaching initiatives are underway, and plans are
      being developed to teach future clinical staff the science of clinician-directed,
      rational use of medical resources. These include pathology, imaging services,
      pharmaceuticals and patient referrals, assisted by published expert guidelines.
      There are significant administrative and personnel issues to surmount, but
      planning for integration has begun, and plans for turning research outcomes into
      clinical care plans are already emerging.

PMID- 22409679
TI  - What is wrong with Medicare?

PMID- 22409680
TI  - National guidelines for regulation of laser sales, training and use are urgently
      needed.

PMID- 22409681
TI  - Stevens-Johnson syndrome after varicella vaccination.

PMID- 22409682
TI  - Not much need for ambulatory blood pressure monitoring.

PMID- 22409683
TI  - The future of fast-food regulation: new research suggests a novel strategy.

PMID- 22409684
TI  - Major haemorrhage in rural Australia: time for a novel solution to a unique
      problem?

PMID- 22409685
TI  - Evaluating workplace-based assessment of interns in a Queensland hospital: does
      the current instrument fit the purpose?

PMID- 22409686
TI  - Dog bites in Australian children.

PMID- 22409687
TI  - A case series of grevillea seed burns.

PMID- 22409688
TI  - Conflict of interest guidelines for clinical guidelines.

PMID- 22409689
TI  - Appropriate indications for computed tomography coronary angiography.
AB  - Computed tomography coronary angiography (CTCA) has been shown in multicentre
      trials to be reliable in ruling out significant coronary artery disease (CAD). It
      is used most appropriately in symptomatic patients with low to intermediate
      pretest probability of CAD. It should not be used in asymptomatic subjects,
      patients with known significant CAD or patients with a high pretest probability
      of CAD. The radiation dose of CTCA was previously two to three times that of
      invasive coronary angiography but with modern protocols, it is similar or lower.
      Patients generally need to be in sinus rhythm, tolerate Beta-blockers and
      nitrates, have a heart rate < 65 beats per minute, be able to hold their breath
      for 10 seconds, and have normal renal function.

PMID- 22409690
TI  - Calciphylaxis and hypoalbuminaemia.

PMID- 22409691
TI  - Guide-wire fragment embolisation in paediatric peripherally inserted central
      catheters.
AB  - OBJECTIVE: To report guide-wire fragment embolisation of paediatric peripherally
      inserted central catheter (PICC) devices and explore the safety profile of four
      commonly used devices. DESIGN, SETTING AND PARTICIPANTS: Clinical incidents
      involving paediatric PICC devices in Queensland public hospitals were reviewed. A
      PICC user-experience survey was conducted at five public hospitals with 32
      clinicians. A device design evaluation was undertaken, and magnetic resonance
      imaging (MRI) safety was tested by a simulation study. MAIN OUTCOME MEASURES:
      Embolisation events; technical mistakes, multiple attempts and breakages during
      insertion; willingness to use the device; failure modes and risk priority rating;
      movement and/or temperature change on exposure to MRI. RESULTS: Six clinical
      incidents of silent guide-wire embolisation, and four near misses were
      identified; all were associated with one type of device. The survey found that
      this device had a reported broken-wire embolisation rate of 0.9/100 insertions
      with no events in other devices; two of the four devices had a higher all-cause
      embolisation rate (3.3/100 insertions v 0.4/100 insertions) and lower clinician
      acceptance (68%-71% v 91%-100%). All devices had 6-17 identified failure modes;
      the two devices that allowed removal of a guide wire through a septum had the
      highest overall risk rating. Guide-wire exposure to MRI was rated a potential
      safety risk due to movement. CONCLUSIONS: There is marked variation in the safety
      profile of 3 Fr PICC devices in clinical use, and safety performance can be
      linked to design factors. Pre-MRI screening of all children who have previously
      had a PICC device inserted is recommended. We advocate a decision-making model
      for evaluation of device safety.

PMID- 22409692
TI  - Medical device regulation in Australia: safe and effective?
AB  - OBJECTIVE: To describe the frequency, characteristics and outcomes of reports of
      possible harms related to medical devices submitted to the Australian Therapeutic
      Goods Administration (TGA) using data made publicly available on the TGA website.
      DESIGN AND SETTING: A retrospective analysis, conducted in January 2012, of data
      made publicly available on the TGA website from January 2000 to December 2011.
      MAIN OUTCOME MEASURES: The number and nature of reports of medical device
      incidents, recalls and alerts. RESULTS: Up to December 2011, 6812 incidents
      involving medical devices were reported to the TGA, although there were several
      periods where data were unavailable. Incidents were reported more frequently in
      later years, most often by device sponsors, and were often attributed to
      mechanical problems. 295 deaths and 2357 serious injuries have been related to
      incidents, with serious injury (597) highest in 2009. Most incidents involving
      medical devices were not investigated (47.5%), or, after investigation, no
      further action was taken (25.0%). During the same time period, there were 35
      medical device recalls and 34 medical device alerts issued by the TGA, with no
      consistent increase over time. CONCLUSIONS: Despite TGA reform proposals, greater
      transparency is still needed. Issues that have not been addressed include patchy
      and conflicting data in the public domain and lack of explanations for the large
      proportion of uninvestigated reports. To maintain public confidence in the
      national regulatory system these problems need to be resolved.

PMID- 22409693
TI  - Patterns and outcomes of preterm hospital admissions during pregnancy in NSW,
      2001-2008.
AB  - OBJECTIVE: To assess the frequency and outcomes of preterm hospital admissions
      during pregnancy, with a focus on transfers to higher levels of care. DESIGN:
      Population-based cohort study using linked population data. SETTING AND SUBJECTS:
      Women who were admitted to hospital in weeks 20-36 of pregnancy (preterm) and
      gave birth to a liveborn singleton infant in New South Wales during 2001-2008.
      MAIN OUTCOME MEASURE: Numbers of preterm admissions of pregnant women who were
      discharged without giving birth, were transferred to higher care, or who gave
      birth. RESULTS: 110,439 pregnancies (16.0%) involved at least one preterm
      admission. After their initial preterm admission, 71.9% of women were discharged,
      6.3% were transferred and 21.8% gave birth. Median gestational age at admission
      was 33 weeks and median time to discharge, transfer or giving birth was 1 day.
      Most women who were transferred or who gave birth had been admitted for preterm
      rupture of membranes or preterm labour. Of the women who were admitted or were
      transferred with suspected preterm labour, only 29% and 38%, respectively, gave
      birth. Compared with other admitted women, women having a first birth, public
      patients and those living in areas of low socioeconomic status were more likely
      to be transferred or to give birth. As gestational age increased, the proportion
      of women transferred decreased and the proportion giving birth increased. Infants
      born after maternal transfer had lower gestational age and more adverse outcomes
      than those born without maternal transfer. CONCLUSIONS: Preterm hospital
      admission affects one in six women with singleton pregnancies. Methods that could
      improve assessment of labour status have a large potential to reduce the burden
      on maternity services. The increased morbidity for infants born after maternal
      transfer suggests women with high-risk pregnancies are being appropriately
      identified.

PMID- 22409694
TI  - Basal-bolus insulin versus sliding-scale insulin for inpatient glycaemic control:
      a clinical practice comparison.
AB  - OBJECTIVE: To determine if the improvement in inpatient glycaemic control
      observed with basal-bolus insulin (BBI) over sliding-scale insulin (SSI) in the
      formal study setting translates to routine clinical conditions. DESIGN, SETTING
      AND PATIENTS: Cross-sectional study in which capillary blood glucose levels
      (BGLs) were prospectively measured four times daily for up to 8 days in 124
      patients with type 2 diabetes admitted to a tertiary teaching hospital and
      treated with BBI between November 2008 and May 2010. Data from the BBI treatment
      group were compared with retrospective data from 96 patients treated with SSI
      between June 2001 and May 2006. MAIN OUTCOME MEASURES: Mean daily BGL;
      independent effect of insulin regimen on mean daily BGL. RESULTS: Mean baseline
      BGL was not significantly different in patients receiving BBI and SSI (mean +/-
      SD, 11.3 +/- 4.1 v 10.6 +/- 4.3 mmol/L; P = 0.23). After the first full day of
      therapy, mean daily BGL for patients receiving BBI was 1.6 +/- 3.7 mmol/L lower
      than baseline BGL, and it remained 1.6-2.4 mmol/L lower than baseline throughout
      the study (P < 0.001). In contrast, there was no significant change in BGL for
      patients receiving SSI. Random effects regression analysis indicated that BBI was
      associated with a significantly lower mean daily BGL than SSI, independent of
      other variables (P < 0.001). The incidence of hypoglycaemia (BGL < 4 mmol/L) was
      significantly greater in patients receiving BBI than SSI (3.3% v 1.4%; P <
      0.001), but there was no significant difference for severe hypoglycaemia (BGL <
      2.8 mmol/L) (0.3 v 0.5%; P = 0.3). CONCLUSIONS: Under routine clinical
      conditions, BBI is effective and safe across a range of patients and appears to
      be superior to SSI. Clinical improvements reflected those seen in a strict formal
      study setting.

PMID- 22409695
TI  - The first year counts: cancer survival among Indigenous and non-Indigenous
      Queenslanders, 1997-2006.
AB  - OBJECTIVE: To examine the differential in cancer survival between Indigenous and
      non-Indigenous people in Queensland in relation to time after diagnosis,
      remoteness and area-socioeconomic disadvantage. DESIGN, SETTING AND PARTICIPANTS:
      Descriptive study of population-based data on all 150,059 Queensland residents of
      known Indigenous status aged 15 years and over who were diagnosed with a primary
      invasive cancer during 1997-2006. MAIN OUTCOME MEASURES: Hazard ratios for the
      categories of area-socioeconomic disadvantage, remoteness and Indigenous status,
      as well as conditional 5-year survival estimates. RESULTS: Five-year survival was
      lower for Indigenous people diagnosed with cancer (50.3%; 95% CI, 47.8%-52.8%)
      compared with non-Indigenous people (61.9%; 95% CI, 61.7%-62.2%). There was no
      evidence that this differential varied by remoteness (P = 0.780) or area
      socioeconomic disadvantage (P = 0.845). However, it did vary by time after
      diagnosis. In a time-varying survival model stratified by age, sex and cancer
      type, the 50% excess mortality in the first year (adjusted HR, 1.50; 95% CI, 1.38
      1.63) reduced to near unity at 2 years after diagnosis (HR, 1.03; 95% CI, 0.78
      1.35). CONCLUSIONS: After a wide disparity in cancer survival in the first 2
      years after diagnosis, Indigenous patients with cancer who survive these 2 years
      have a similar outlook to non-Indigenous patients. Access to services and
      socioeconomic factors are unlikely to be the main causes of the early lower
      Indigenous survival, as patterns were similar across remoteness and area
      socioeconomic disadvantage. There is an urgent need to identify the factors
      leading to poor outcomes early after diagnosis among Indigenous people with
      cancer.

PMID- 22409696
TI  - Stories of the music of hope.

PMID- 22409697
TI  - Too much care--not enough love?

PMID- 22409699
TI  - Predictors of physical activity among rural and small town breast cancer
      survivors: an application of the theory of planned behaviour.
AB  - The primary objective of this study was to investigate the utility of the two
      component theory of planned behaviour (TPB) in understanding physical activity
      intentions and behaviour in rural and small town breast cancer survivors. The
      secondary objective was to elicit the most common behavioural, normative and
      control beliefs of rural and small town survivors regarding physical activity.
      Using a cross-sectional survey design, 524 rural and small town breast cancer
      survivors completed a mailed survey that assessed physical activity and TPB
      variables. Physical activity intention explained 12% of the variance in physical
      activity behaviour (p < 0.01) while the TPB constructs together explained 43% of
      the variance in physical activity intention (p < 0.01). Unique behavioural,
      normative and control beliefs were elicited from the sample. The two-component
      TPB framework appears to be a suitable model to initiate an understanding of
      physical activity determinants among rural and small town breast cancer
      survivors. These data can be used in the development and establishment of
      physical activity behaviour interventions and health promotion materials designed
      to facilitate physical activity behaviour among rural and small town breast
      cancer survivors.

PMID- 22409701
TI  - The prevalence of metabolic syndrome in clomiphene citrate resistant polycystic
      ovary syndrome.
AB  - OBJECTIVE: To investigate the prevalence of metabolic syndrome in clomiphene
      citrate (CC) resistant polycystic ovary syndrome (PCOS) patients. METHODS: 58 CC
      resistant PCOS patients, 52 CC responders, 53 fertile PCOS and 53 age and body
      mass index-matched normoandrogenic ovulatory fertile women were evaluated for
      metabolic syndrome. RESULTS: Metabolic syndrome prevalence was 41.4% in CC
      resistants, in 23.1% of CC responders, in 11.3% of PCOS fertiles and 0% of
      controls (p < 0.0001). Waist circumference (WC) > 88 cm was 44.8%, systolic blood
      pressure (BP) >= 130 mmHg and diastolic BP >=85 mmHg were 27.6%, TG
      (triglyceride) >=150 mg/dL was 36.2%, HDL(high density lipoprotein) < 50 mg/dL
      was 63.8%, fasting glucose levels >= 100 mg/dL was 20.7% in CC resistant PCOS
      women. There were positive associations between CC resistance and WC >88 cm, BP
      >= 130 >= 85 mmHg, TG >= 150 mg/dL, HDL < 50 mg/dL, fasting glucose >= 100 mg/dL,
      and presence of metabolic syndrome (p < 0.05, for all). Moreover, WC > 88 cm, and
      HDL < 50 mg/dL were independent variables that were associated by CC resistance
      by multivariate regression analysis. CONCLUSIONS: CC resistant PCOS patients have
      high prevalence of metabolic syndrome. These women have an increased risk of
      future cardiovascular disease.

PMID- 22409700
TI  - Emotions and suicidal ideation among depressed women with childhood sexual abuse
      histories.
AB  - Depressed women with sexual abuse histories have a heightened risk of suicidal
      ideation (SI), which may be only in part attributable to psychiatric symptoms of
      depression and posttraumatic stress disorder (PTSD). Emotions and SI were studied
      among 106 women with histories of childhood sexual abuse enrolled in treatment
      trials for major depression. Assessments were conducted at baseline, 10, 24, and
      36 weeks. Sadness, guilt, and shame-proneness were associated with self-reported
      and observer-rated SI across time after adjusting for depressive and PTSD
      symptoms, suicide attempt history, and sociodemographic characteristics
      associated with SI. These findings highlight the need for clinical attention to
      self-directed negative emotions to potentially reduce suicide-related risk.

PMID- 22409703
TI  - Postsynthetic modification of peptides via chemoselective N-alkylation of their
      side chains.
AB  - A chemoselective, mild, and versatile method for performing postsynthetic
      modifications of peptide sequences is described. It requires only activated
      molecular sieves in the presence of an alkyl halide in order to N-alkylate lysine
      side chains. This reaction is fully compatible with most of the peptide
      functionalities, discriminates the reactivity of differently protected lysines,
      and proceeds in good yield. The mild conditions employed were further proved by
      performing the N-alkylation of a peptide containing a disulfide bridge.

PMID- 22409704
TI  - Accuracy of CBCT and 3D Stereolithographic Model in Identifying the Anterior Loop
      of the Mental Nerve: A Study on Cadavers.
AB  - Abstract   AbstractThe objective of this ex vivo cadaver study was to determine
      the accuracy of cone beam computed tomography(CBCT) and 3D
      stereolithographic(STL) model in identifying and measuring the anterior loop
      length(ANLL) of the mental nerve. A total of 12 cadavers (24 mental nerve plexus)
      were used for this study. Standardized CBCT scans of each mandible were obtained
      both with and without radiographic contrast tracer injected into the mental nerve
      plexus. STL models of the two acquired CBCT images were made. ANLL were measured
      using CBCT, STL and anatomy. The measurements obtained from the CBCT images and
      STL models were then analyzed and compared with the direct anatomic measurements.
      Paired sample t-test was used. P values less than .05 was considered
      statistically significant. The mean difference between CBCT and anatomic
      measurement was 0.04mm and not statistically significant (p= .332) while the mean
      difference between STL and anatomic measurement was 0.4mm and statistically
      significant (p=.042). There was also a statistical significant difference between
      CBCT and STL (p=.048) with the mean difference  of 0.35mm. Therefore, CBCT is an
      accurate and reliable method in determining and measuring the ANLL while the STL
      over or underestimated the ANLL by as much as 1.51mm and 1.83mm respectively.

PMID- 22409705
TI  - Thorium(IV)-selenate clusters containing an octanuclear Th(IV) hydroxide/oxide
      core.
AB  - Four Th(IV) hydroxide/oxide clusters have been synthesized from aqueous solution.
      The structures of [Th(8)(MU(3)-O)(4)(MU(2)-OH)(8)(H(2)O)(15)(SeO(4))(8).7.5H(2)O]
      (1), [Th(8)(MU(3)-O)(4)(MU(2)-OH)(8)(H(2)O)(17)(SeO(4))(8).nH(2)O] (2),
      [Th(9)(MU(3)-O)(4)(MU(2)-OH)(8)(H(2)O)(21)(SeO(4))(10)] (3), and Th(9)(MU(3)
      O)(4)(MU(2)-OH)(8)(H(2)O)(21)(SeO(4))(10).nH(2)O (4) were determined using single
      crystal X-ray diffraction. Each structure consists of an octanuclear core,
      [Th(8)O(4)(OH)(8)](16+), that is built from eight Th(IV) atoms (four Th in a
      plane and two up and two down) linked by four "inner" MU(3)-O and eight "outer"
      MU(2)-OH groups. Compounds 3 and 4 additionally contain mononuclear
      [Th(H(2)O)(5)(SeO(4))(4)](4-) units that link the octamers into an extended
      structure. The octanuclear units are invariably complexed by two selenate anions
      that sit in two cavities formed by four planar Th(IV) and four extra-planar
      Th(IV) atoms, thus making [Th(8)O(4)(OH)(8)(SeO(4))(2)](12+) a common building
      block in 1-4. However, changes in hydration as well selenate coordination give
      rise to structural differences that are observed in the extended structures of 1
      4. The compounds were also characterized by Raman spectroscopy. Density
      functional theory calculations were performed to predict the geometries,
      vibrational frequencies, and relative energies of different structures. Details
      of the calculated structures are in good agreement with experimental results, and
      the calculated frequencies were used to assign the experimental Raman spectra. On
      the basis of an analysis of the DFT results, the compound
      Th(8)O(8)(OH)(4)(SeO(4))(6) was predicted to be a strong gas phase acid but is
      reduced to a weak acid in aqueous solution. Of the species studied
      computationally, the dication Th(8)O(6)(OH)(6)(SeO(6))(6)(2+) is predicted to be
      the most stable in aqueous solution at 298 K followed by the monocation
      Th(8)O(7)(OH)(5)(SeO(6))(6)(+).

PMID- 22409706
TI  - Synteny-based mapping-by-sequencing enabled by targeted enrichment.
AB  - Mapping-by-sequencing, as implemented in SHOREmap ('SHOREmapping'), is greatly
      accelerating the identification of causal mutations. The original SHOREmap
      approach based on resequencing of bulked segregants required a highly accurate
      and complete reference sequence. However, current whole-genome or transcriptome
      assemblies from next-generation sequencing data of non-model organisms do not
      produce chromosome-length scaffolds. We have therefore developed a method that
      exploits synteny with a related genome for genetic mapping. We first demonstrate
      how mapping-by-sequencing can be performed using a reduced number of markers, and
      how the associated decrease in the number of markers can be compensated for by
      enrichment of marker sequences. As proof of concept, we apply this method to
      Arabidopsis thaliana gene models ordered by synteny with the genome sequence of
      the distant relative Brassica rapa, whose genome has several large-scale
      rearrangements relative to A. thaliana. Our approach provides an alternative
      method for high-resolution genetic mapping in species that lack finished genome
      reference sequences or for which only RNA-seq assemblies are available. Finally,
      for improved identification of causal mutations by fine-mapping, we introduce a
      new likelihood ratio test statistic, transforming local allele frequency
      estimations into a confidence interval similar to conventional mapping intervals.

PMID- 22409708
TI  - Effect of weave, structural parameters and ultraviolet absorbers on in vitro
      protection factor of bleached cotton woven fabrics.
AB  - INTRODUCTION: The weave, fabric cover, areal density and ultraviolet (UV)
      absorbers are some of the factors which influence the ultraviolet protection
      factor (UPF) of cotton fabrics. It will be of interest to know whether fabric
      cover or fabric areal density is a better predictor of cotton fabric UPF. It will
      also be of interest to know whether the UV absorbers are equally effective for
      all kinds of cotton fabric. OBJECTIVES: To understand the role of weave, fabric
      cover, areal density and UV absorbers on the UPF of cotton fabrics. To establish
      quantitative relationships between the fabric cover, areal density and UPF for
      cotton fabrics. METHODS: Sixty-four woven fabrics were manufactured using
      different weaves, cotton yarn count and picks per centimetre values. Nonlinear
      regression models were developed to relate the fabric cover and areal density
      with the UPF. The role of UV absorbers at different levels of cover has been
      analysed. RESULTS: In case of bleached cotton fabrics woven with 40 Ne warp yarn
      count, 40 ends per cm, different weft yarn count (20-40 Ne) and picks per
      centimetre (15-27), weave does not have a statistically significant effect on the
      UPF. Fabric areal density is a better predictor of UPF than the fabric cover. The
      UV absorbers are more effective when the fabric cover is high. CONCLUSIONS: The
      developed equations relating fabric cover and UPF can be used as a primary
      guideline while selecting fabrics for UV protection.

PMID- 22409709
TI  - Role of non-surgical therapies in the management of periocular basal cell
      carcinoma and squamous intra-epidermal carcinoma: a case series and review of the
      literature.
AB  - BACKGROUND: Basal cell carcinoma (BCC) and squamous intra-epidermal carcinoma
      (IEC) are the most common periocular tumours and can be associated with
      significant morbidity. Five percent of imiquimod cream and photodynamic therapy
      (PDT) are popular non-surgical treatment options but are currently not licensed
      for periocular use. OBJECTIVES: To review our experience with these treatments
      and summarize published literature (PubMed: up to September 2011). PATIENTS AND
      METHODS: We conducted a review of case notes for all patients with periocular BCC
      and IEC treated with either PDT or imiquimod, within National Health Service
      (NHS) Tayside, Scotland, from 1996 to 2009. RESULTS: Six of 13 and five of 12
      lesions treated with imiquimod (median duration of clearance=35 months; range=24
      55 months) and PDT (median duration of clearance=66 months; range=4-80 months),
      respectively, achieved clinical clearance. The majority of patients in our series
      did manage to tolerate and continue both treatments, with no significant longer
      term adverse effects. CONCLUSIONS: Our limited experience along with published
      reports suggests that both imiquimod and PDT are effective in the treatment of
      periocular non-melanoma skin cancers in selected patients. However, surgical
      excision with margin control remains the gold standard for the treatment of
      periocular tumours.

PMID- 22409710
TI  - Validation of a novel high-intensity LED light source for skin phototesting at
      365 nm.
AB  - BACKGROUND: The gold standard for investigation of patients with suspected
      photosensitivity involves phototesting on non-exposed skin with an irradiation
      monochromator (IM). However, this device is bulky, expensive and only available
      at a small number of specialised photodermatology units. We have developed a
      small handheld high output monochromatic light source for phototesting to UVA at
      365 nm using light-emitting diodes (LEDs). METHODS: A UNO light engine (Enfis,
      Swansea, UK) at 365 nm was used to develop a handheld intense source. Seventy
      seven normal healthy volunteers were phototested on the lower back with the LED
      source and with an IM at 365 nm. Minimal erythema dose (MED) at 24 h was assessed
      visually and by a diffuse reflectance erythemameter. RESULTS: In 77 volunteers,
      MED levels for the two sources agreed in 66 out of 77 cases (85.7%). In a further
      10 out of 77 patients, the measured MED elicited by the LED source was 1 dose
      level higher than the monochromator MED. CONCLUSION: A high-intensity portable
      and low cost LED phototesting device was developed. The results confirm that
      phototesting to UVA at 365 nm using this LED light source compares favourably to
      monochromator light testing at this wavelength.

PMID- 22409711
TI  - A comparative study on efficacy of UVA1 vs. narrow-band UVB phototherapy in the
      treatment of vitiligo.
AB  - BACKGROUND/PURPOSE: Narrow-band ultraviolet B (NB-UVB) is considered the most
      effective and safe initial treatment for moderate-to-severe vitiligo but
      phototoxicity and possible carcinogenicity are the reported side effects.
      Ultraviolet A1 (UVA1) phototherapy has overlapping biological effects to NB-UVB
      and is relatively free of side effects associated with other phototherapy
      regimens. METHODS: Forty patients with vitiligo were included in this
      prospective, randomized controlled comparative clinical trial. Twenty patients
      received NB-UVB and 20 received UVA1 three times weekly for 12 weeks. The UVA1
      group was divided into two subgroups. Ten patients received moderate and 10
      received low dose of UVA1. Serum samples were collected before and after 36
      sessions to assess soluble interleukin 2 receptor level. Patients were clinically
      evaluated before therapy then monthly according to Vitiligo Area Scoring Index
      (VASI) and Vitiligo European Task Force (VETF) scores. In addition, extent of
      response was determined by a blinded dermatologist comparing before and after
      therapy photographs. Pattern of response and side effects were recorded. RESULTS:
      NB-UVB was superior to UVA1 with a significant difference in blinded
      dermatological assessment (P<0.001), percentage change in VASI score (P<0.001)
      and percentage change in VETF area score (P=0.001). No significant difference in
      side effects was observed between both groups. Comparing UVA1 subgroups, better
      response in moderate-dose group was found as regard to percentage change in VASI
      (P<0.001) and percentage change in VETF area score (P=0.001), while no
      significant difference was found in blinded dermatological assessment (P=0.121).
      CONCLUSION: NB-UVB phototherapy remains to be an effective and safe therapeutic
      option in vitiligo. Response to UVA1 in vitiligo seems to be dose dependent and
      seems to be of limited value in treatment of vitiligo as a monotherapy. Further
      studies combining it with other lines of therapy such as systemic steroids may
      prove beneficial.

PMID- 22409712
TI  - Prevalence and predictors of low vitamin D status in patients referred to a
      tertiary photodiagnostic service: a retrospective study.
AB  - BACKGROUND/PURPOSE: Low vitamin D levels have been associated with adverse
      effects on health. The primary source of vitamin D is cutaneous production during
      sunlight exposure. Sun avoidance can restrict vitamin D photosynthesis and is
      common practice amongst patients with photosensitivity. Few studies have examined
      vitamin D status in this population, particularly those in northern latitudes.
      The purpose of this study was therefore to investigate the prevalence and
      possible predictors of low vitamin D status in patients referred to a tertiary
      photodiagnostic service. METHODS: A case note review of 165 patients who attended
      the National Photodiagnostic Service for assessment at the Photobiology Unit in
      Dundee, Scotland (latitude 56  degrees N) over 1 year was conducted. Clinical
      information and serum 25-hydroxyvitamin D (25(OH)D) concentration were
      documented. Multivariate analyses were used to identify predictors of vitamin D
      status. RESULTS: Mean 25(OH)D concentration was 41.9 nmol/L [standard deviation
      (SD) 22.0]. Forty percent of patients had insufficient vitamin D levels [25(OH)D
      25-49 nmol/L] and 25% were vitamin D deficient [25(OH)D<25 nmol/L]. Blood
      collection in winter was the strongest predictor of low 25(OH)D status (P<0.001);
      strict photoprotection (P=0.04), onset of symptoms within an hour of sunlight
      exposure (P=0.01) and abnormal monochromator phototesting responses (P=0.009)
      also predicted low vitamin D levels. Supplement use was associated with higher
      vitamin D levels (P<0.001), even amongst patients who strictly avoided sunlight
      (P=0.03). CONCLUSIONS: Patients with photosensitivity who live in northern
      latitudes are at high risk of low vitamin D levels, particularly in winter and
      spring. Increased awareness of this risk is crucial to ensure preventative
      strategies, such as supplementation, are implemented.

PMID- 22409713
TI  - Treatment of oral lichen planus with methylene blue mediated photodynamic therapy
      -a clinical study.
AB  - BACKGROUND/PURPOSE: Oral lichen planus is an autoimmune disorder that has posed a
      challenge in spite of the several treatment modalities available. Here, we have
      proposed yet another treatment modality, photodynamic therapy, for this
      condition. The aim of the study was to treat patients having symptomatic oral
      lichen planus with photodynamic therapy with methylene blue as photosensitizer.
      METHODS: Twenty patients with symptomatic oral lichen planus were included in the
      study. They were treated with 5% methylene blue mediated photodynamic therapy
      (light source: Xenon arc lamp, wavelength: 630 +/- 5 nm, total dose: 120 J/cm(2)
      per sitting) in four sessions (1st, 4th, 7th and 15th day). Follow-up was done on
      second and fourth week after the therapy. RESULTS: There was significant
      improvement in signs and symptoms of the lesion at first and second follow-up
      visits (P-value<0.001). CONCLUSION: There was satisfactory reduction in signs and
      symptoms of oral lichen planus without any side effects. Thus, methylene blue
      mediated photodynamic therapy seems to be a promising alternative for the control
      of oral lichen planus.

PMID- 22409714
TI  - Photodynamic therapy for the treatment of folliculitis decalvans.
AB  - Folliculitis decalvans is a chronic form of deep folliculitis that occurs on the
      scalp as patches of scarring alopecia at the expanding margins of which are
      follicular pustules. Treatment of folliculitis decalvans is extremely difficult
      with a resultant poor prognosis. Photodynamic therapy has been reported to be
      effective in disorders as acne or folliculitis. We report one patient with
      folliculitis decalvans who was successfully treated with photodynamic therapy.

PMID- 22409715
TI  - Photolocalized purpura during levofloxacin therapy.
AB  - Side-effects associated with levofloxacin treatment include phototoxicity,
      hypersensitivity and skin disorders. Purpuric eruptions have rarely been
      reported. We describe the case of a 75-year-old woman who was prescribed a 15-day
      course of levofloxacin (500 mg twice a day) for hemorrhagic cystitis. On exposure
      to sunlight, the patient developed a pruritic purpuric eruption on the lower
      extremities. The acute reaction differed from a classical sunburn, manifesting as
      confluent petechiae limited to sun-exposed areas and accompanied by pruritus.
      This was a rare case of solar capillaritis. Purpuric eruptions on photoexposed
      skin should be considered another unusual side effect of levofloxacin.

PMID- 22409717
TI  - Lower urinary tract symptoms and urinary incontinence in a geriatric cohort - a
      population-based analysis.
AB  - OBJECTIVES: To assess prevalence and severity of lower urinary tract function in
      85-year-old men and women. Little is known on the prevalence of lower urinary
      tract dysfunction in this geriatric age group, which is now the fastest growing
      sector of the population worldwide. PATIENTS AND METHODS: The Vienna Trans-Danube
      Aging study (VITA) is a longitudinal, population-based study initiated in 2000
      that included men/women aged 75 years living in a well-defined area in Vienna.
      The main purpose of the VITA study was to identify risk factors for incident
      Alzheimer's disease. All study participants alive in 2010 were contacted by mail
      to complete a detailed questionnaire on various aspects of lower urinary tract
      symptoms (LUTS) and urinary incontinence (UI). RESULTS: The response rate was
      68%, resulting in a total of 262 questionnaires available for analysis (men n=
      96; women n= 166). All study participants were 85 years of age. Urinary
      incontinence defined as any involuntary loss during the past 4 weeks was reported
      by 24% of men and 35% of women (P= 0.04). Stress UI was more frequent in women
      (39%) than in men (14%, P < 0.01), the difference for urge UI (women 35%, men
      25%) was on the border of statistical significance (P= 0.05). Only four
      individuals (1.5%) needed permanent catheterization. Urgency (women 56%, men 54%)
      and daytime frequency (women 70%, men 74%) were equally distributed (P > 0.05).
      Nocturia more often than twice was more prevalent in men (69%) than in women
      (49%) (P= 0.02). Overactive bladder, according to International Continence
      Society criteria, was present in 55% of women and 50% of men. No difference
      regarding quality of life impairment as the result of LUTS and UI was noticed
      between sexes. A few co-morbidities were identified to correlate with UI and
      storage symptoms. CONCLUSIONS: These data provide insights into the prevalence
      and severity of LUTS and UI in individuals in their eighties, to our knowledge
      the largest population-based study in this age group. Demographic changes in
      upcoming decades underline the importance of a thorough understanding of lower
      urinary tract dysfunction in a geriatric population.

PMID- 22409718
TI  - Comparison of uniaxial and triaxial accelerometry in the assessment of physical
      activity among adolescents under free-living conditions: the HELENA study.
AB  - BACKGROUND: Different types of devices are available and the choice about which
      to use depends on various factors: cost, physical characteristics, performance,
      and the validity and intra- and interinstrument reliability. Given the large
      number of studies that have used uniaxial or triaxial devices, it is of interest
      to know whether the different devices give similar information about PA levels
      and patterns. The aim of this study was to compare physical activity (PA) levels
      and patterns obtained simultaneously by triaxial accelerometry and uniaxial
      accelerometry in adolescents in free-living conditions. METHODS: Sixty-two
      participants, aged 13-16 years, were recruited in this ancillary study, which is
      a part of the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA).
      All participants wore a uniaxial accelerometer (ActiGraph GT1M(r), Pensacola, FL)
      and a triaxial accelerometer (RT3(r), Stayhealthy, Monrovia, CA) simultaneously
      for 7 days. The patterns were calculated by converting accelerometer data output
      as a percentage of time spent at sedentary, light, moderate, and vigorous PA per
      day. Analysis of output data from the two accelerometers were assessed by two
      different tests: Equivalence Test and Bland & Altman method. RESULTS: The
      concordance correlation coefficient between the data from the triaxial
      accelerometer and uniaxial accelerometer at each intensity level was superior to
      0.95. The ANOVA test showed a significant difference for the first three lower
      intensities while no significant difference was found for vigorous intensity. The
      difference between data obtained with the triaxial accelerometer and the uniaxial
      monitor never exceeded 2.1% and decreased as PA level increased. The Bland &
      Altman method showed good agreement between data obtained between the both
      accelerometers (p < 0.05). CONCLUSIONS: Uniaxial and triaxial accelerometers do
      not differ in their measurement of PA in population studies, and either could be
      used in such studies.

PMID- 22409719
TI  - Distinct dimerization for various alloforms of the amyloid-beta protein: Abeta(1
      40), Abeta(1-42), and Abeta(1-40)(D23N).
AB  - The Amyloid-beta protein is related to Alzheimer's disease, and various
      experiments have shown that oligomers as small as the dimer are cytotoxic. Two
      alloforms are mainly produced: Abeta(1-40) and Abeta(1-42). They have very
      different oligomer distributions, and it was recently suggested, from
      experimental studies, that this variation may originate from structural
      differences in their dimer structures. Little structural information is available
      on the Abeta dimer, however, and to complement experimental observations, we
      simulated the folding of the wild-type Abeta(1-40) and Abeta(1-42) dimers as well
      as the mutated Abeta(1-40)(D23N) dimer using an accurate coarse-grained force
      field coupled to Hamiltonian-temperature replica exchange molecular dynamics. The
      D23N variant impedes the salt-bridge formation between D23 and K28 seen in the
      wild-type Abeta, leading to very different fibrillation properties and final
      amyloid fibrils. Our results show that the Abeta(1-42) dimer has a higher
      propensity than the Abeta(1-40) dimer to form beta-strands at the central
      hydrophobic core (residues 17-21) and at the C-terminal (residues 30-42), which
      are two segments crucial to the oligomerization of Abeta. The free energy
      landscape of the Abeta(1-42) dimer is also broader and more complex than that of
      the Abeta(1-40) dimer. Interestingly, D23N also impacts the free energy landscape
      by increasing the population of configurations with higher beta-strand
      propensities when compared against Abeta(40). In addition, while Abeta(1
      40)(D23N) displays a higher beta-strand propensity at the C-terminal, its solvent
      accessibility does not change with respect to the wild-type sequence. Overall,
      our results show the strong impact of the two amino acids Ile41-Ala42 and the
      salt-bridge D23-K28 on the folding of the Abeta dimer.

PMID- 22409720
TI  - Effect of supplemental feeding with glycerol or propylene glycol in early
      lactation on the fertility of Swedish dairy cows.
AB  - The aim of this field study was to evaluate the effect of supplemental feeding
      with glycerol (GLY) or propylene glycol (PG) during early lactation on the
      fertility of Swedish dairy cows. Within 17 commercial dairy herds, 798 cows were
      randomized to three groups that were daily fed supplements with 450 g GLY, 300 g
      PG or nothing (control, C). The supplements were given twice daily during 0-21
      days in milk as a top dress on concentrates. Data on calving date, insemination
      dates, gynaecological examinations, as well as breed, parity and monthly milk
      yield were collected. From a subset of 308 cows in seven herds, milk samples for
      progesterone analysis were taken twice weekly and used to determine the time for
      onset of luteal activity. The effects of supplements on the intervals from
      calving to first luteal activity (FLA), first AI (FAI) and conception (CON),
      respectively, were analysed using semi-parametric survival models (Cox
      proportional hazards models) controlling for the effect of parity, breed, calving
      season, milk yield and the clustering effect of herd. There was no difference in
      time to FLA between the cows in group C and in group GLY or PG. No differences in
      time to FAI or in time to CON were found between cows in group PG and group C.
      However, cows in the GLY group tended to get their FAI later compared with cows
      in the control group but without at subsequent delaying of time to CON.

PMID- 22409721
TI  - Polyelectrolyte multilayers as a platform for luminescent nanocrystal patterned
      assemblies.
AB  - The fabrication of uniform and patterned nanocrystal (NC) assemblies has been
      investigated by exploiting the possibility of carefully tailoring colloidal NC
      surface chemistry and the ability of polyelectrolyte (PE) to functionalize
      substrates through an electrostatic layer-by-layer (LbL) strategy. Appropriate
      deposition conditions, substrate functionalization, and post-preparative
      treatments were selected to tailor the substrate surface chemistry to effectively
      direct the homogeneous electrostatic-induced assembly of NCs. Water-dispersible
      luminescent NCs, namely, (CdSe)ZnS and CdS, were differently functionalized by
      (1) ligand-exchange reaction, (2) growth of a hydrophilic silica shell, and (3)
      formation of a hydrophilic inclusion complex, thus providing functional NCs
      stable in a defined pH range. The electrostatically charged functional NCs
      represent a comprehensive selection of examples of surface-functionalized NCs,
      which enables the systematic investigation of experimental parameters in NC
      assembly processes carried out by combining LbL procedures with microcontact
      printing and also exploiting NC emission, relevant for potential applications, as
      a prompt and effective probe for evaluating assembly quality. Thus, an ample
      showcase of combinations has been investigated, and the spectroscopic and
      morphological features of the resulting NC-based structures have been discussed.

PMID- 22409722
TI  - Helping parents of children with monogenetic disorders understand developmental
      trajectories: lessons from achondroplasia.

PMID- 22409723
TI  - Optimization of potent hepatitis C virus NS3 helicase inhibitors isolated from
      the yellow dyes thioflavine S and primuline.
AB  - A screen for hepatitis C virus (HCV) NS3 helicase inhibitors revealed that the
      commercial dye thioflavine S was the most potent inhibitor of NS3-catalyzed DNA
      and RNA unwinding in the 827-compound National Cancer Institute Mechanistic Set.
      Thioflavine S and the related dye primuline were separated here into their pure
      components, all of which were oligomers of substituted benzothiazoles. The most
      potent compound (P4), a benzothiazole tetramer, inhibited unwinding >50% at 2 +/-
      1 MUM, inhibited the subgenomic HCV replicon at 10 MUM, and was not toxic at 100
      MUM. Because P4 also interacted with DNA, more specific analogues were
      synthesized from the abundant dimeric component of primuline. Some of the 32
      analogues prepared retained ability to inhibit HCV helicase but did not appear to
      interact with DNA. The most potent of these specific helicase inhibitors
      (compound 17) was active against the replicon and inhibited the helicase more
      than 50% at 2.6 +/- 1 MUM.

PMID- 22409725
TI  - Massign: an assignment strategy for maximizing information from the mass spectra
      of heterogeneous protein assemblies.
AB  - Electrospray ionization mass spectrometry (ESI-MS) has evolved into a powerful
      adjunct for structural biology, helping to unravel the quaternary structure of
      protein complexes. Increasing interest has led to the study of ever larger
      multicomponent systems. Investigating these large complexes with ESI has meant
      that progressively more complicated mass spectra have been recorded. Correct
      assignment of these spectra is essential to maximize the information content
      available. Here we present a new assignment strategy and a supporting software
      package that allows the investigation of large heterogeneous systems, previously
      beyond the scope of full spectral assignment due to their complexity. The
      strategy involves two parts. The first includes a peak fitting routine to
      determine charge state distributions and consequently the masses of the various
      subcomplexes. The second module distinguishes between solution and gas phase
      products depending on their mass to charge ratio and assigns these charge states
      to different subunit combinations. These fitting and assignment routines contain
      many internal checks for consistency and reveal mass shifts, dependent upon
      desolvation conditions and small molecule binding. Using a rotary ATPase as a
      working example, we show how this assignment strategy is capable of determining
      the stoichiometry and interactions of the 8 different subunits within this 29
      subunit assembly.

PMID- 22409724
TI  - Analysis of the inhibition and remodeling of islet amyloid polypeptide amyloid
      fibers by flavanols.
AB  - Islet amyloid polypeptide (IAPP, amylin) is responsible for amyloid formation in
      type 2 diabetes and in transplanted islets. The flavanol (-)-epigallocatechin-3
      gallate [EGCG; (2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-1
      benzopyran-3-yl 3,4,5-trihydroxybenzoate] is an effective inhibitor of amyloid
      formation by IAPP; however, the interactions required for the inhibition of IAPP
      amyloid formation and for the remodeling of amyloid fibers are not known. A range
      of features have been proposed to be critical for EGCG protein interactions,
      including interactions with aromatic residues, interactions with amino groups, or
      sulfhydryls. Using a set of IAPP analogues, we show that none of these are
      required. Studies in which EGCG is added to the lag phase of amyloid formation
      shows that it interacts with intermediates as well as with monomers and amyloid.
      The features of EGCG required for effective inhibition were examined. The
      stereoisomer of EGCG, (-)-gallocatechin gallate (GCG), is an effective inhibitor,
      although less so than EGCG. Removing the gallate ester moiety leads to EGC which
      is a less effective inhibitor. Removing only the 3-hydroxyl group of the
      trihydroxyphenyl ring leads to a compound that has more pronounced effects on the
      lag phase than EGC but is less effective at reducing the amount of amyloid.
      Elimination of both the 3-hydroxy group and the gallate ester results in loss of
      activity. EGCG remodels IAPP amyloid fibers but does not fully resolubilize them
      to unstructured monomers, and the remodeling is not the reverse of amyloid
      assembly. The ability of the compounds to remodel IAPP amyloid closely follows
      their relative ability to inhibit amyloid formation.

PMID- 22409727
TI  - Time to scrap the U.S. system of medical device regulation?

PMID- 22409726
TI  - Spermidine application to young developing peach fruits leads to a slowing down
      of ripening by impairing ripening-related ethylene and auxin metabolism and
      signaling.
AB  - Peach (Prunus persica var. laevis Gray) was chosen to unravel the molecular basis
      underlying the ability of spermidine (Sd) to influence fruit development and
      ripening. Field applications of 1 mM Sd on peach fruit at an early developmental
      stage, 41 days after full bloom (dAFB), i.e. at late stage S1, led to a slowing
      down of fruit ripening. At commercial harvest (125 dAFB, S4II) Sd-treated fruits
      showed a reduced ethylene production and flesh softening. The endogenous
      concentration of free and insoluble conjugated polyamines (PAs) increased (0.3
      2.6-fold) 1 day after treatment (short-term response) butsoon it declined to
      control levels; starting from S3/S4, when soluble conjugated forms increased (up
      to five-fold relative to controls at ripening), PA levels became more abundant in
      treated fruits, (long-term response). Real-time reverse transcription-polymerase
      chain reaction analyses revealed that peaks in transcript levels of fruit
      developmental marker genes were shifted ahead in accord with a developmental
      slowing down. At ripening (S4I-S4II) the upregulation of the ethylene
      biosynthetic genes ACO1 and ACS1 was dramatically counteracted by Sd and this led
      to a strong downregulation of genes responsible for fruit softening, such as PG
      and PMEI. Auxin-related gene expression was also altered both in the short term
      (TRPB) and in the long term (GH3, TIR1 and PIN1), indicating that auxin plays
      different roles during development and ripening processes. Messenger RNA amounts
      of other hormone-related ripening-regulated genes, such as NCED and GA2-OX, were
      strongly downregulated at maturity. Results suggest that Sd interferes with fruit
      development/ripening by interacting with multiple hormonal pathways.

PMID- 22409730
TI  - Suppressive effects of nonsteroidal anti-inflammatory drugs diclofenac sodium,
      salicylate and indomethacin on delayed rectifier K+-channel currents in murine
      thymocytes.
AB  - Lymphocytes predominantly express delayed rectifier K(+)-channels (Kv1.3) in
      their plasma membranes, and the channels play crucial roles in the lymphocyte
      activation and proliferation. Since nonsteroidal anti-inflammatory drugs
      (NSAIDs), the most commonly used analgesic and antipyretic drugs, exert
      immunomodulatory effects, they would affect the channel currents in lymphocytes.
      In the present study, employing the standard patch-clamp whole-cell recording
      technique, we examined the effects of diclofenac sodium, salicylate and
      indomethacin on the channel currents in murine thymocytes and the membrane
      capacitance. Diclofenac sodium and salicylate significantly suppressed the pulse
      end currents of the channel. However, indomethacin suppressed both the peak and
      the pulse-end currents with a significant increase in the membrane capacitance.
      This study demonstrated for the first time that NSAIDs, such as diclofenac
      sodium, salicylate and indomethacin, exert inhibitory effects on thymocyte Kv1.3
      channel currents. The slow inactivation pattern induced by indomethacin was
      thought to be associated with microscopic changes in the plasma membrane surface
      detected by the increase in the membrane capacitance.

PMID- 22409731
TI  - Enzymatic reductions for the regio- and stereoselective synthesis of hydroxy-keto
      esters and dihydroxy esters.
AB  - Ketoreductases were utilized for the stereoselective synthesis of delta-hydroxy
      beta-keto esters, beta-hydroxy-delta-keto esters, and beta,delta-dihydroxy
      esters. Seven out of eight possible stereoisomers were obtained from the
      enzymatic reduction of the corresponding beta,delta-diketo ester in high enantio-
      and diastereomeric excess.

PMID- 22409733
TI  - Immediate placement and provisionalization of single-tooth implants involving a
      definitive individual abutment: a clinical and radiographic retrospective study.
AB  - AIM: To assess with a mean follow-up period of 33 months (median: 31 month,
      range: 11-89 month) the treatment outcome after immediate placement and
      provisionalization of single-tooth oral implants involving a definitive
      individual abutment and a provisional crown followed by later placement of a
      definitive crown. MATERIALS AND METHODS: 68 patients with 68 single-tooth
      implants in the esthetic zone were consecutively treated; 55 of these patients
      were included in the study. The treatment involved tooth extraction, implant
      placement, placement of a definitive individual abutment, and a provisional crown
      in the same visit in private practice. The definitive crown was placed after a
      mean period of 7 months. The primary outcome measures included implant survival,
      definitive implant crown survival, and overall treatment survival. The secondary
      outcome measures included probing depth, bleeding on probing, peri-implant
      marginal bone level, marginal bone level of the neighboring tooth surfaces,
      biological complications, and technical complications. RESULTS: Of the inserted
      implants 98% survived and of the definitive crowns mounted a survival of 100% was
      observed. Consequently, the overall treatment survival was 98%. The mean probing
      depth was 2.9 mm at implant level and 63% of the implants were characterized by
      no bleeding on probing. The mean peri-implant marginal bone level was 2 mm. A
      significant mean peri-implant marginal bone level gain of 0.5 mm was observed
      from implant placement to the follow-up (95% CI: 0.07-0.89 mm, P = 0.022). No
      significant changes of the marginal bone level at the neighboring tooth surfaces
      were seen. Four episodes of peri-implant inflammation were identified in three
      patients, while 46 incidents of loosening of the provisional crown occurred in 33
      patients. One abutment screw loosened before placement of the definitive crown.
      Finally, loosening of four definitive crowns occurred in four patients.
      CONCLUSIONS: Immediate placement and provisionalization of single-tooth oral
      implants involving a definitive individual abutment and a provisional crown
      followed by later placement of a definitive crown were characterized by high
      survival of the implant crowns and implants as well as healthy peri-implant
      tissues, after a mean follow-up period of 33 months. Loss of retention of the
      provisional crown occurred frequently.

PMID- 22409732
TI  - Hospital-level associations with 30-day patient mortality after cardiac surgery:
      a tutorial on the application and interpretation of marginal and multilevel
      logistic regression.
AB  - BACKGROUND: Marginal and multilevel logistic regression methods can estimate
      associations between hospital-level factors and patient-level 30-day mortality
      outcomes after cardiac surgery. However, it is not widely understood how the
      interpretation of hospital-level effects differs between these methods. METHODS:
      The Australasian Society of Cardiac and Thoracic Surgeons (ASCTS) registry
      provided data on 32,354 patients undergoing cardiac surgery in 18 hospitals from
      2001 to 2009. The logistic regression methods related 30-day mortality after
      surgery to hospital characteristics with concurrent adjustment for patient
      characteristics. RESULTS: Hospital-level mortality rates varied from 1.0% to 4.1%
      of patients. Ordinary, marginal and multilevel regression methods differed with
      regard to point estimates and conclusions on statistical significance for
      hospital-level risk factors; ordinary logistic regression giving inappropriately
      narrow confidence intervals. The median odds ratio, MOR, from the multilevel
      model was 1.2 whereas ORs for most patient-level characteristics were of greater
      magnitude suggesting that unexplained between-hospital variation was not as
      relevant as patient-level characteristics for understanding mortality rates. For
      hospital-level characteristics in the multilevel model, 80% interval ORs, IOR
      80%, supplemented the usual ORs from the logistic regression. The IOR-80% was
      (0.8 to 1.8) for academic affiliation and (0.6 to 1.3) for the median annual
      number of cardiac surgery procedures. The width of these intervals reflected the
      unexplained variation between hospitals in mortality rates; the inclusion of one
      in each interval suggested an inability to add meaningfully to explaining
      variation in mortality rates. CONCLUSIONS: Marginal and multilevel models take
      different approaches to account for correlation between patients within hospitals
      and they lead to different interpretations for hospital-level odds ratios.

PMID- 22409734
TI  - Dental pain in Brazilian schoolchildren: a cross-sectional study.
AB  - AIM: To estimate the prevalence, intensity and associated factors of dental pain
      in 7- and 8-year-old schoolchildren in a Southern Brazilian city. DESIGN: A cross
      sectional study was carried out involving a representative sample (n=401) of
      schoolchildren of Tubarao, Brazil. The data were obtained through oral
      examinations, following WHO criteria. Dental pain was analysed using a specific
      questionnaire developed to measure it. Prevalence and intensity of spontaneous
      pain and pain caused by cold and hot food and liquids were analysed. Association
      studies were carried out using chi-square test followed by nonconditional
      multiple logistic regression analysis to test for independence of association
      between outcomes and explanatory variables. RESULTS: The prevalence of
      spontaneous dental pain and dental pain caused by cold and hot food and liquids
      was 31.7 and 28.1%, respectively. Females and schoolchildren who had visited the
      dentist at least once showed statistically higher prevalence of spontaneous pain
      and pain caused by cold and hot food and liquids. Eight-year-old schoolchildren
      and those presenting cavities in the primary dentition also showed higher
      prevalence of spontaneous dental pain. CONCLUSIONS: The prevalence and intensity
      of dental pain were considered high. The prevalence showed to be associated with
      female gender, higher age, the presence of cavities in the primary dentition and
      dental visit.

PMID- 22409735
TI  - Health-promoting interventions for persons aged 80 and older are successful in
      the short term--results from the randomized and three-armed Elderly Persons in
      the Risk Zone study.
AB  - OBJECTIVES: To examine the outcomes of the Elderly Persons in the Risk Zone
      study, which was designed to evaluate whether it is possible to delay
      deterioration if a health-promoting intervention is made when an older adult
      (>=80) is at risk of becoming frail and whether a multiprofessional group
      intervention is more effective in delaying deterioration than a single preventive
      home visit with regard to frailty, self-rated health, and activities of daily
      living (ADLs) at 3-month follow-up. DESIGN: Randomized, three-armed, single
      blind, controlled trial performed between November 2007 and May 2011. SETTING:
      Two urban districts of Gothenburg, Sweden. PARTICIPANTS: Four hundred fifty-nine
      community-living adults aged 80 and older not dependent on the municipal home
      help service. INTERVENTION: A preventive home visit or four weekly
      multiprofessional senior group meetings with one follow-up home visit.
      MEASUREMENTS: Change in frailty, self-rated health, and ADLs between baseline and
      3-month follow-up. RESULTS: Both interventions delayed deterioration of self
      rated health (odds ratio (OR) = 1.99, 95% confidence interval (CI) = 1.12-3.54).
      Senior meetings were the most beneficial intervention for postponing dependence
      in ADLs (OR = 1.95, 95% CI = 1.14-3.33). No effect on frailty could be
      demonstrated. CONCLUSION: Health-promoting interventions made when older adults
      are at risk of becoming frail can delay deterioration in self-rated health and
      ADLs in the short term. A multiprofessional group intervention such as the senior
      meetings described seems to have a greater effect on delaying deterioration in
      ADLs than a single preventive home visit. Further research is needed to examine
      the outcome in the long term and in different contexts.

PMID- 22409736
TI  - First manic episode revealing cerebellar stroke.

PMID- 22409737
TI  - Chorea and a frontal lobe syndrome: a rare neurological presentation of
      polycythemia vera; a case report.

PMID- 22409738
TI  - Quality of life as a determinant of frailty phenotype in community-dwelling
      persons with Parkinson's disease.

PMID- 22409739
TI  - The relationship between serum resistin level and the components of metabolic
      syndrome in elderly Chinese men.

PMID- 22409740
TI  - Differentiation of dementia with Lewy bodies from Alzheimer's disease using the
      Japanese version of the Test Your Memory.

PMID- 22409741
TI  - Test Your Memory test, Arabic version: is it practical in a different culture?

PMID- 22409742
TI  - Please tell people with Alzheimer's disease not to drive.

PMID- 22409743
TI  - Better characterization of transient ischemic attack might improve the benefit:
      risk profile of thrombolysis.

PMID- 22409744
TI  - Telomere length and high-density lipoprotein cholesterol.

PMID- 22409747
TI  - Capacity building of nurses providing neonatal care in Rio de Janeiro, Brazil:
      methods for the POINTS of care project to enhance nursing education and reduce
      adverse neonatal outcomes.
AB  - BACKGROUND: Increased survival of preterm infants in developing countries has
      often been accompanied by increased morbidity. A previous study found rates of
      severe retinopathy of prematurity varied widely between different neonatal units
      in Rio de Janeiro. Nurses have a key role in the care of high-risk infants but
      often do not have access to ongoing education programmes. We set out to design a
      quality improvement project that would provide nurses with the training and tools
      to decrease neonatal mortality and morbidity. The purpose of this report is to
      describe the methods and make the teaching package (POINTS of care--six modules
      addressing Pain control; optimal Oxygenation; Infection control; Nutrition
      interventions; Temperature control; Supportive care) available to others.
      METHODS/DESIGN: Six neonatal units, caring for 40% of preterm infants in Rio de
      Janeiro were invited to participate. In Phase 1 of the study multidisciplinary
      workshops were held in each neonatal unit to identify the neonatal morbidities of
      interest and to plan for data collection. In Phase 2 the teaching package was
      developed and tested. Phase 3 consisted of 12 months data collection utilizing a
      simple tick-sheet for recording. In Phase 4 (the Intervention) all nurses were
      asked to complete all six modules of the POINTS of care package, which was
      supplemented by practical demonstrations. Phase 5 consisted of a further 12
      months data collection. In Phase 1 it was agreed to include inborn infants with
      birthweight <= 1500 g or gestational age of <= 34 weeks. The primary outcome was
      death before discharge and secondary outcomes included retinopathy of prematurity
      and bronchopulmonary dysplasia. Assuming 400-450 infants in both pre- and post
      intervention periods the study had 80% power at p = < 0.05 to detect an increase
      in survival from 68% to 80%; a reduction in need for supplementary oxygen at 36
      weeks post menstrual age from 11% to 5.5% and a reduction in retinopathy of
      prematurity requiring treatment from 7% to 2.5%. DISCUSSION: The results of the
      POINTS of Care intervention will be presented in a separate publication. TRIAL
      REGISTRATION: Current Controlled Trials: ISRCTN83110114.

PMID- 22409749
TI  - Phylogenetic studies of three sinipercid fishes (Perciformes: Sinipercidae) based
      on complete mitochondrial DNA sequences.
AB  - The sinipercids are a group of 12 species of freshwater percoid fish endemic to
      East Asia and their phylogenetic placements have perplexed generations of
      taxonomists. We cloned and sequenced the complete mitochondrial DNA (mtDNA) of
      three sinipercid fishes (Siniperca chuatsi, S. kneri, and S. scherzeri) to
      characterize and compare their mitochondrial genomes. The mitochondrial genomes
      of S. chuatsi, S. kneri, and S. scherzeri were 16,496, 17,002, and 16,585 bp in
      length, respectively. The organization of the three mitochondrial genomes is
      similar to those reported from other fish mitochondrial genomes, which contains
      37 genes (13 protein-coding genes, 2 ribosomal RNAs, and 22 transfer RNAs) and a
      major non-coding control region. Among the 13 protein-coding genes of all the
      three sinipercid fishes, three reading-frame overlaps were found on the same
      strand. There is an 81-bp tandem repeat cluster at the end of CSB-3 in the S.
      scherzeri control region. The complete mitochondrial genomes of the three
      sinipercids should be useful for the evolutionary studies of sinipercids and
      other vertebrate species.

PMID- 22409748
TI  - Genetic diversity analysis of Arius manillensis (Siluriformes: Ariidae) using the
      mitochondrial control region.
AB  - Arius manillensis is a Philippine endemic species and is an economically
      important fishery resource in Laguna de Bay, the largest lake in the country.
      Drastic reduction in population sizes of A. manillensis has been recorded in the
      past, which may have resulted in genetic bottleneck. In this study, the genetic
      diversity and population structure of A. manillensis in Laguna de Bay were
      assessed using the mitochondrial DNA control region. Specimens were obtained from
      three localities along Laguna de Bay, namely Binangonan (n = 27), Tanay (n = 29),
      and Calamba (n = 30). Of the 86 DNA sequences generated, 22 distinct haplotypes
      were observed. There were four unique haplotypes for Binangonan, six for Calamba,
      and five for Tanay. There were two haplotypes common to the three sites. The
      maximum likelihood tree and median-joining network showed little geographic
      separation among the haplotypes. Chi-square test showed no significant
      differentiation in A. manillensis from the three sites. The overall computed
      F(ST) was 0.0144, indicating small genetic differentiation in A. manillensis from
      the three localities sampled. Likewise, analysis of molecular variance showed a
      greater percentage of variation within population (98.62%) than variation among
      populations (1.38%; P = 0.21). Total haplotype diversity and nucleotide diversity
      among the specimens from the three sites were 0.775 and 0.013, respectively. The
      high haplotype diversity coupled with low nucleotide diversity observed in this
      study confirms that genetic bottleneck occurred in A. manillensis which was
      followed by population expansion. This is also supported by the non-significant
      values for both Tajima's D and Fu's F. Furthermore, multimodal mismatch
      distribution plots were generated, which is consistent with the model of spatial
      range expansion followed by demographic expansion.

PMID- 22409750
TI  - The complete mitochondrial genomes of largemouth bass of the northern subspecies
      (Micropterus salmoides salmoides) and Florida subspecies (Micropterus salmoides
      floridanus) and their applications in the identification of largemouth bass
      species.
AB  - The largemouth bass belongs to the family Centrarchidae, which includes two
      subspecies: the northern subspecies, Micropterus salmoides salmoides, and the
      Florida subspecies, Micropterus salmoides floridanus. In this study, the complete
      mitochondrial genomes of the two subspecies were sequenced, and their genetic
      differences were identified. The mitogenomes of M. s. salmoides and M. s.
      floridanus are 16,486 and 16,479 bp in length, respectively. The two subspecies
      consisted of 37 genes (13 protein-coding genes, 2 ribosomal RNA, and 22 transfer
      RNA), which are typical for vertebrate mtDNA. Phylogenetic analysis provided
      statistical support for the monophyly of the family Centrarchidae. Comparison of
      the two subspecies' mitogenomes revealed a relatively high number (450) of single
      nucleotide polymorphisms (SNPs) in protein-coding genes. We characterized SNPs in
      the partial cytochrome c oxidase subunit 1 gene of different individuals from
      three cultured populations, one wild northern subspecies population, and one wild
      Florida subspecies population. Twenty-eight SNPs were fixed with alternative
      nucleotides in the two subspecies, which could be used for differentiating them.
      Based on this gene, phylogenetic tree and genetic distance analyses supported
      that cultured largemouth bass in China belongs to the northern subspecies.

PMID- 22409751
TI  - Mitochondrial genome of the Siberian sturgeon Acipenser baerii.
AB  - The complete mitochondrial genome of Siberian sturgeon Acipenser baerii had been
      determined. The total length of the mitogenome was 16,763 bp and had 13 protein
      coding, 22 tRNA, and 2 rRNA genes. Except for the eight tRNA and Nd6 genes, all
      other mitochondrial genes are encoded on the heavy strand. The overall base
      composition of the heavy strand is 30.3% A, 24.3% T, 29.1% C, 16.3% G, with an AT
      content of 54.6%. The DNA sequence of A. baerii shared 97.8, 97.6, 93.5, 91.6,
      93.6, and 87.1% sequence homology with that of Acipenser sinensis, Acipenser
      gueldenstaedtii, Acipenser transmontanus, Acipenser dabryanus, Acipenser
      stellatus, and Polyodon spathula. Molecular data presented here provide a useful
      tool for evolutionary as well as population genetics studied.

PMID- 22409752
TI  - Highly conserved d-loop sequences in woolly mouse opossums Marmosa (Micoureus).
AB  - This study reports the occurrence of highly conserved d-loop sequences in the
      mitochondrial genome of the woolly mouse opossum genus Marmosa subgenus Micoureus
      (Mammalia, Didelphimorphia, Didelphidae). Sixty-six sequences of Marmosa
      (Micoureus) demerarae, Marmosa (Micoureus) constantiae, and Marmosa (Micoureus)
      paraguayanus were amplified using universal d-loop primers and virtually no
      genetic differences were detected within and among species. These sequences
      matched the control region of the mitochondrial marsupial genome. Analyses of
      qualitative aspects of these sequences revealed that their structural composition
      is very similar to the d-loop region of other didelphid species. However, the
      total lack of variability has not been reported from other closely related
      species. The data analyzed here support the occurrence of highly conserved d-loop
      sequences, and we found no support for the hypothesis that these sequences are d
      loop-like nuclear pseudogenes. Furthermore, the control and flanking regions
      obtained with different primers corroborate the lack of variability of the d-loop
      sequences in the mitochondrial genome of Marmosa (Micoureus).

PMID- 22409753
TI  - Complete mitochondrial genome of the Teinopalpus aureus guangxiensis
      (Lepidoptera: Papilionidae) and related phylogenetic analyses.
AB  - In this study, we sequenced the complete mitochondrial genome of Teinopalpus
      aureus guangxiensis (Lepidoptera: Papilionidae), which is considered as an
      endemic species in China. It is listed as a vulnerable species by International
      Union for Conservation of Nature and Natural Resources Red List and also a first
      class endangered species in China. The complete mtDNA from T. aureus guangxiensis
      was 15,235 base pairs in length and contained 13 protein-coding genes (PCGs), 2
      rRNA genes, 22 tRNA genes, and a control region. The T. aureus guangxiensis genes
      were in the same order and orientation as the completely sequenced mitogenomes of
      other lepidopteran species. All PCGs of T. aureus guangxiensis mitogenome start
      with a typical ATN codon and terminate in the common stop codon TAA, except that
      ND1 gene uses TTA, ND3 gene uses ATT, and ND4 and ND4L gene use TAA. The
      phylogenetic relationships were reconstructed with the concatenated sequences of
      the 13 PCGs of the mitochondrial genome, and phylogenetic results confirmed that
      Nymphalidae, Lycaenidae, Papilionidae, Pieridae are monophyletic clades.

PMID- 22409755
TI  - Complete mitochondrial genome of the red drum, Sciaenops ocellatus (Perciformes,
      Sciaenidae): absence of the typical conserved motif in the origin of the light
      strand replication.
AB  - In this study, the complete mitochondrial genome of the red drum Sciaenops
      ocellatus was determined first. The genome was 16,500 bp in length and contained
      13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and 2 main
      non-coding regions (the control region and the origin of the light-strand
      replication); the gene composition and order of which were similar to most other
      vertebrates. The overall base composition of the heavy strand was T 25.5%, C
      30.7%, A 27.5%, and G 16.3%, with a slight AT bias of 53%. Within the control
      region, the discrete and conserved sequence blocks were identified. Motif 5'
      ACCGG-3' rather than 5'-GCCGG-3' was detected in the origin of light-strand
      replication (O(L)) of red drum, which is rare in the mitogenomes of Sciaenidae
      species. These results would play an important role in elucidating sequence
      function relationships of the O(L).

PMID- 22409756
TI  - Complete mitochondrial genome of the Bewick's swan Cygnus columbianus bewickii
      (Aves, Anseriformes, Anatidae).
AB  - The mitochondrial genome of Bewick's swan Cygnus columbianus bewickii was
      completely sequenced and then the resultant data were compared with those of the
      whistling swan Cygnus columbianus columbianus. The complete mitochondrial genome
      sequence of C. c. bewickii was 16,727 bp in length and its gene arrangement
      pattern, gene content, and genome organization were identical to those of Cygnus
      species. The similarities of nucleotide and amino acid sequences between the two
      swans were 99.1% and 99.6%, respectively. Out of the 13 protein-coding genes and
      2 rRNA genes, COIII showed the lowest nucleotide sequence similarity with 98.0%.
      On the other hand, in amino acid sequence similarities, both COII and ATP6 showed
      the lowest with 98.7% in common. The control region has the 97.8% nucleotide
      sequence similarity.

PMID- 22409757
TI  - Complete mitochondrial genome of the peregrine falcon Falco peregrinus (Aves,
      Falconiformes, Falconidae): genetic differences between the two individuals.
AB  - The peregrine falcon Falco peregrinus (Aves, Falconiformes, Falconidae) is one of
      the most common and widespread raptor species in the world. Here, the complete
      mitochondrial genome of F. peregrinus from Korea, which is one of the breeding
      ranges, was sequenced and characterized in detail.

PMID- 22409758
TI  - Complete mitochondrial genome of the longtooth grouper Epinephelus bruneus
      (Perciformes, Serranidae).
AB  - We determined the complete nucleotide sequence of the mitochondrial (mt) genome
      for the longtooth grouper, Epinephelus bruneus (Perciformes, Serranidae). This mt
      genome, consisting of 16,686 base pairs (bp), encoded genes for 13 protein-coding
      genes, 2 ribosomal RNAs, 22 transfer RNAs, and a noncoding control region as
      those found in other vertebrates, with the gene order identical to that of
      typical vertebrates. A major noncoding region between the trnP and trnF genes
      (991 bp) was considered to be the control region (D-loop). Within this sequence,
      22 copies of a 17-bp tandem repeat element, 5'-TGATATTACATATATGC-3', were
      identified in the control region unlike previous reported Epinephelus species.

PMID- 22409759
TI  - The complete mitochondrial genome of the striped field mouse, Apodemus agrarius
      (Rodentia, Murinae) from Korea.
AB  - The striped field mouse, Apodemus agrarius, is the most common rodents in
      temperate forests of the Korean peninsula. We have determined the complete
      mitochondrial genome (JN629047) of A. agrarius from Korea. Apodemus agrarius
      mitogenome is 16,263 bp in length and has a base composition of 33.9% A, 29.9% T,
      23.6% C, and 12.5% G. The total length of the 13 protein-coding genes is 11,398
      bp long.

PMID- 22409760
TI  - Complete mitochondiral genome of the Korean red fox Vulpes vulpes (Carnivora,
      Canidae).
AB  - The complete mitochondrial genome sequence of Vulpes vulpes consists of 13
      protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1 control region (CR). CR
      is located between the tRNA-Pro and tRNA-Phe genes and is 1173 base pairs (bp) in
      length. It consists of a short non-repetitive sequence followed by 8-bp 5'
      ACACACGT-3' tandem repeat between conserved sequence black I and conserved
      sequence black II.

PMID- 22409761
TI  - The complete mitochondrial genome of the Korean red-backed vole, Myodes regulus
      (Rodentia, Murinae) from Korea.
AB  - We have determined the complete mitochondrial genome (NC_016427) of the Korean
      red-backed vole, Myodes regulus, which is distributed in South Korea. The total
      length of the M. regulus mitogenome is 16,379 bp, with a base composition of
      33.0% A, 26.7% T, 27.1% C, and 13.2% G. The total length of the 13 protein-coding
      genes is 11,396 bp long.

PMID- 22409762
TI  - Complete mitochondrial genome of the jackknife clam Solen grandis (Veneroida,
      Solenidae).
AB  - The complete mitochondrial genome sequence of Solen grandis that lives in sub
      tidal waters and being buried in muddy to fine sand substrates, is described in
      this paper. The mitogenome (16,794 bp) consists of 12 protein-coding genes (loss
      of ATPase subunit 8), 22 tRNA genes, 2 rRNA genes and 1 putative control region.
      It is the typical bivalve mitochondrial gene composition.

PMID- 22409763
TI  - Low resolution of mitochondrial COI barcodes for identifying species of the genus
      Larus (Charadriiformes: Laridae).
AB  - We evaluated whether cytochrome c oxidase subunit I (COI) barcodes that have been
      previously suggested for birds are useful for identifying species of the genus
      Larus, which are resident or migratory birds in Korea. We found 31 intra- or
      interspecific COI haplotypes from 12 of 13 Larus species in Korea. Haplotype
      analyses showed that the COI barcodes could not distinguish some interspecific
      haplotypes from 6 of 12 Larus species because there were no nucleotide
      substitutions among their COI haplotypes. The neighbor-joining tree formed
      shallow branches in the clades expected for L. saundersi, L. crassirostris, L.
      canus, L relictus, and L. ridbundus. In the nine Larus species, COI haplotypes
      were not grouped as distinct entities that were correctly assigned to their
      corresponding species, resulting in polytypic clades. These results indicate that
      the COI sequences need to be cautiously selected as a DNA barcode for identifying
      species of Korean Larus birds.

PMID- 22409764
TI  - Contributions of domain-general cognitive resources and different forms of
      arithmetic development to pre-algebraic knowledge.
AB  - The purpose of this study was to investigate the contributions of domain-general
      cognitive resources and different forms of arithmetic development to individual
      differences in pre-algebraic knowledge. Children (n = 279, mean age = 7.59 years)
      were assessed on 7 domain-general cognitive resources as well as arithmetic
      calculations and word problems at start of 2nd grade and on calculations, word
      problems, and pre-algebraic knowledge at end of 3rd grade. Multilevel path
      analysis, controlling for instructional effects associated with the sequence of
      classrooms in which students were nested across Grades 2-3, indicated arithmetic
      calculations and word problems are foundational to pre-algebraic knowledge. Also,
      results revealed direct contributions of nonverbal reasoning and oral language to
      pre-algebraic knowledge, beyond indirect effects that are mediated via arithmetic
      calculations and word problems. By contrast, attentive behavior, phonological
      processing, and processing speed contributed to pre-algebraic knowledge only
      indirectly via arithmetic calculations and word problems.

PMID- 22409766
TI  - Mindfulness training effects for parents and educators of children with special
      needs.
AB  - Parents and teachers of children with special needs face unique social-emotional
      challenges in carrying out their caregiving roles. Stress associated with these
      roles impacts parents' and special educators' health and well-being, as well as
      the quality of their parenting and teaching. No rigorous studies have assessed
      whether mindfulness training (MT) might be an effective strategy to reduce stress
      and cultivate well-being and positive caregiving in these adults. This randomized
      controlled study assessed the efficacy of a 5-week MT program for parents and
      educators of children with special needs. Participants receiving MT showed
      significant reductions in stress and anxiety and increased mindfulness, self
      compassion, and personal growth at program completion and at 2 months follow-up
      in contrast to waiting-list controls. Relational competence also showed
      significant positive changes, with medium-to-large effect sizes noted on measures
      of empathic concern and forgiveness. MT significantly influenced caregiving
      competence specific to teaching. Mindfulness changes at program completion
      mediated outcomes at follow-up, suggesting its importance in maintaining
      emotional balance and facilitating well-being in parents and teachers of children
      with developmental challenges.

PMID- 22409765
TI  - An ecological analysis of the effects of deviant peer clustering on sexual
      promiscuity, problem behavior, and childbearing from early adolescence to
      adulthood: an enhancement of the life history framework.
AB  - The authors propose that peer relationships should be included in a life history
      perspective on adolescent problem behavior. Longitudinal analyses were used to
      examine deviant peer clustering as the mediating link between attenuated family
      ties, peer marginalization, and social disadvantage in early adolescence and
      sexual promiscuity in middle adolescence and childbearing by early adulthood.
      Specifically, 998 youths, along with their families, were assessed at age 11
      years and periodically through age 24 years. Structural equation modeling
      revealed that the peer-enhanced life history model provided a good fit to the
      longitudinal data, with deviant peer clustering strongly predicting adolescent
      sexual promiscuity and other correlated problem behaviors. Sexual promiscuity, as
      expected, also strongly predicted the number of children by ages 22-24 years.
      Consistent with a life history perspective, family social disadvantage directly
      predicted deviant peer clustering and number of children in early adulthood,
      controlling for all other variables in the model. These data suggest that deviant
      peer clustering is a core dimension of a fast life history strategy, with strong
      links to sexual activity and childbearing. The implications of these findings are
      discussed with respect to the need to integrate an evolutionary-based model of
      self-organized peer groups in developmental and intervention science.

PMID- 22409768
TI  - Extreme differences in oxidation states: synthesis and structural analysis of the
      germanide oxometallates A10[Ge9]2[WO4] as well as A(10+x)[Ge9]2[W(1-x)Nb(x)O4]
      with A = K and Rb containing [Ge9]4- polyanions.
AB  - Semitransparent dark-red or ruby-red moisture- and air-sensitive single crystals
      of A(10+x)[Ge(9)](2)[W(1-x)Nb(x)O(4)] (A = K, Rb; x = 0, 0.35) were obtained by
      high-temperature solid-state reactions. The crystal structure of the compounds
      was determined by single-crystal X-ray diffraction experiments. They crystallize
      in a new structure type (P2(1)/c, Z = 4) with a = 13.908(1) A, b = 15.909(1) A, c
      = 17.383(1) A, and beta = 90.050(6) degrees  for
      K(10.35(1))[Ge(9)](2)[W(0.65(1))Nb(0.35(1))O(4)]; a = 14.361(3) A, b = 16.356(3)
      A, c = 17.839(4) A, and beta = 90.01(3) degrees  for
      Rb(10.35(1))[Ge(9)](2)[W(0.65(1))Nb(0.35(1))O(4)]; a = 13.8979(2) A, b =
      15.5390(3) A, c = 17.4007(3) A, and beta = 90.188(1) degrees  for
      K(10)[Ge(9)](2)WO(4); and a = 14.3230(7) A, b = 15.9060(9) A, c = 17.8634(9) A,
      and beta = 90.078(4) degrees  for Rb(10)[Ge(9)](2)WO(4). The compounds contain
      discrete Ge(9)(4-) Wade's nido clusters and WO(4)(2-) (or NbO(4)(3-)) anions,
      which are packed according to a hierarchical atom-to-cluster replacement of the
      Al(2)Cu prototype and are separated by K and Rb cations, respectively. The alkali
      metal atoms occupy the corresponding tetrahedral sites of the Al(2)Cu prototype.
      The amount of the alkali metal atoms on these diamagnetic compounds corresponds
      directly to the amount of W substituted by Nb. Thus, the transition metals W and
      Nb appear with oxidation numbers +6 and +5, respectively, in the vicinity of a
      [Ge(9)](4-) polyanion. The crystals of the mixed salts were further characterized
      by Raman spectroscopy. The Raman data are in good agreement with the results from
      the X-ray structural analyses.

PMID- 22409767
TI  - The effect of tobacco and alcohol and their reduction/cessation on mortality in
      oral cancer patients: short communication.
AB  - BACKGROUND: The use of tobacco is known to increase the incidence of developing
      oral cancer by 6 times, while the additive effect of drinking alcohol further
      increases the risk leading to higher rate of morbidity and mortality. In this
      short communication, we prospectively assessed the effect of tobacco smoking and
      alcohol drinking in oral cancer patients on the overall mortality from the
      disease, as well as the effect of smoking and drinking reduction/cessation at
      time of diagnosis on mortality in the same group. MATERIALS AND METHODS: A
      cohort, involved 67 male patients who were diagnosed with oral squamous cell
      carcinoma, was included in this study. The smoking and drinking habits of this
      group were recorded, in addition to reduction/cessation after diagnosis with the
      disease. Comparisons were made to disease mortality at 3 and 5 years. RESULTS:
      Follow-up resulted in a 3-year survival of 46.8% and a 5-year survival of 40.4%.
      Reduction of tobacco smoking and smoking cessation led to a significant reduction
      in mortality at 3 (P < 0.001) and 5 (P < 0.001) years. Reduction in drinking
      alcohol and drinking cessation led to a significant reduction in mortality at 3
      (P < 0.001) and 5 (P < 0.001) years. CONCLUSION: Chronic smoking and drinking
      does have an adverse effect on patients with oral cancer leading to increased
      mortality from cancer-related causes. Reduction/cessation of these habits tends
      to significantly reduce mortality in this group of patients. Smoking and drinking
      cessation counseling should be provided to all newly diagnosed oral cancer
      patients.

PMID- 22409769
TI  - Persistence with prescribed antimuscarinic therapy for overactive bladder: a UK
      experience.
AB  - Study Type--Therapy (prevalence) Level of Evidence 2b. What's known on the
      subject? and What does the study add? Persistence with long-term medication in
      chronic diseases is typically low and that for overactive bladder medication is
      lower than average. Sub-optimal persistence is a major challenge for the
      successful management of overactive bladder. Using UK prescription data,
      persistence was generally low across the range of antimuscarinics. Patients aged
      60 years and above were more likely to persist with prescribed oral
      antimuscarinic drugs than younger patients (40-59 years). Solifenacin was
      consistently associated with the highest rate of persistence compared with the
      other antimuscarinics included in the study OBJECTIVES: * To describe the level
      of persistence for patients receiving antimuscarinics for overactive bladder
      (OAB) over a 12-month period based on real prescription data from the UK. * To
      investigate patterns of persistence with oral antimuscarinic drugs prescribed for
      OAB, across different age groups. PATIENTS AND METHODS: * UK prescription data
      from a longitudinal patient database were analysed retrospectively to assess
      persistence with darifenacin, flavoxate, oxybutynin (extended release [ER] and
      immediate release [IR]), propiverine, solifenacin, tolterodine (ER/IR) and
      trospium. * Data were extracted from the medical records of >1,200,000 registered
      patients via general practice software, and anonymized prescription data were
      collated for all eligible patients with documented OAB (n = 4833). * Data were
      collected on patients who started treatment between January 2007 and December
      2007 and were collected up to December 2008, to allow each patient a full 12
      month potential treatment period. Failure of persistence was declared after a gap
      of at least 1.5 times the length of the period of the most recent prescription. *
      The analysis included only patients who were new to a course of treatment (i.e.
      who had not been prescribed that particular treatment or dosage for at least 6
      months before the study period). RESULTS: * The number of patients prescribed
      each antimuscarinic drug varied from 23 for darifenacin to 1758 for tolterodine
      ER. * The longest mean persistence was reported for solifenacin (187 days versus
      77-157 days for the other treatments). * At 3 months, the proportions of patients
      still on their original treatment were: solifenacin 58%, darifenacin 52%,
      tolterodine ER 47%, propiverine 47%, tolterodine IR 46%, oxybutynin ER 44%,
      trospium 42%, oxybutynin IR 40%, flavoxate 28%. * At 12 months, the proportions
      of patients still on their original treatment were: solifenacin 35%, tolterodine
      ER 28%, propiverine 27%, oxybutynin ER 26%, trospium 26%, tolterodine IR 24%,
      oxybutynin IR 22%, darifenacin 17%, flavoxate 14%. * In a sub-analysis stratified
      by age, patients aged >= 60 years were more likely to persist with prescribed
      therapy over the 12-month period than those aged <60 years. CONCLUSIONS: * Twelve
      months after the initial prescription, persistence rates with pharmacotherapy in
      the context of OAB are generally low. * Solifenacin was associated with higher
      levels of persistence compared with other prescribed antimuscarinic agents. *
      Older people are more likely than younger patients to persist with prescribed
      therapy. Further studies are required to understand this finding and why patients
      are more likely to persist with one drug rather than another.

PMID- 22409770
TI  - Conference highlights of the 5th international workshop on HIV persistence during
      therapy, 6-9 December 2011, St. Maartin, West Indies.
AB  - The December 2011 5th International Workshop on HIV Persistence during Therapy
      addressed the issue of HIV persistence among 210 scientists from 10 countries
      involved in the study of HIV reservoirs and the search of an HIV cure. High
      quality abstracts were selected and discussed as oral or poster presentations.
      The aim of this review is to distribute the scientific highlights of this
      workshop outside the group as analyzed and represented by experts in
      retrovirology, immunology and clinical research.

PMID- 22409771
TI  - Synthesis of novel 6-(4-substituted piperazine-1-yl)-9-(beta-D
      ribofuranosyl)purine derivatives, which lead to senescence-induced cell death in
      liver cancer cells.
AB  - Novel purine ribonucleoside analogues (9-13) containing a 4-substituted
      piperazine in the substituent at N(6) were synthesized and evaluated for their
      cytotoxicity on Huh7, HepG2, FOCUS, Mahlavu liver, MCF7 breast, and HCT116 colon
      carcinoma cell lines. The purine nucleoside analogues were analyzed initially by
      an anticancer drug-screening method based on a sulforhodamine B assay. Two
      nucleoside derivatives with promising cytotoxic activities (11 and 12) were
      further analyzed on the hepatoma cells. The N(6)-(4
      Trifluoromethylphenyl)piperazine analogue 11 displayed the best antitumor
      activity, with IC(50) values between 5.2 and 9.2 MUM. Similar to previously
      described nucleoside analogues, compound 11 also interferes with cellular ATP
      reserves, possibly through influencing cellular kinase activities. Furthermore,
      the novel nucleoside analogue 11 was shown to induce senescence-associated cell
      death, as demonstrated by the SAbeta-gal assay. The senescence-dependent
      cytotoxic effect of 11 was also confirmed through phosphorylation of the Rb
      protein by p15(INK4b) overexpression in the presence of this compound.

PMID- 22409772
TI  - Electronic absorption line shapes at the water liquid/vapor interface.
AB  - In order to investigate the factors that contribute to the electronic absorption
      line shape of a chromophore adsorbed at the water liquid/vapor interface,
      molecular dynamics simulations of a series of dipolar solutes undergoing various
      electronic transitions at various locations along the interface normal are
      studied. For electronic transitions that involve a change in the permanent dipole
      moment of the solute, the transition from the bulk water to the liquid/vapor
      interface involves a spectral shift consistent with the lower polarity of the
      interface. The change in the spectral width relative to that in the bulk is
      determined by several factors, which, depending on the nature of the transition
      and the dipole moment of the initial state, can result in a narrowing or
      broadening of the spectrum. These factors include the location of the interface
      region (which directly correlates with local polarity), the heterogeneity of the
      local solvation shell, and the width of the surface region. The contribution of
      the heterogeneity of the local solvation shell can be determined by comparing
      surface water with bulk methanol, whose polarity is comparable to one of the
      surface regions.

PMID- 22409773
TI  - Cardiolipin synthase is required for Streptomyces coelicolor morphogenesis.
AB  - The fluid mosaic model has recently been amended to account for the existence of
      membrane domains enriched in certain phospholipids. In rod-shaped bacteria, the
      anionic phospholipid cardiolipin is enriched at the cell poles but its role in
      the morphogenesis of the filamentous bacterium Streptomyces coelicolor is
      unknown. It was impossible to delete clsA (cardiolipin synthase; SCO1389) unless
      complemented by a second copy of clsA elsewhere in the chromosome. When placed
      under the control of an inducible promoter, clsA expression, phospholipid profile
      and morphogenesis became inducer dependent. TLC analysis of phospholipid showed
      altered profiles upon depletion of clsA expression. Analysis of cardiolipin by
      mass spectrometry showed two distinct cardiolipin envelopes that reflected
      differences in acyl chain length; the level of the larger cardiolipin envelope
      was reduced in concert with clsA expression. ClsA-EGFP did not localize to
      specific locations, but cardiolipin itself showed enrichment at hyphal tips,
      branch points and anucleate regions. Quantitative analysis of hyphal dimensions
      showed that the mycelial architecture and the erection of aerial hyphae were
      affected by the expression of clsA. Overexpression of clsA resulted in weakened
      hyphal tips, misshaped aerial hyphae and anucleate spores and demonstrates that
      cardiolipin synthesis is a requirement for morphogenesis in Streptomyces.

PMID- 22409774
TI  - Is blood pressure reduction a valid surrogate endpoint for stroke prevention? An
      analysis incorporating a systematic review of randomised controlled trials, a by
      trial weighted errors-in-variables regression, the surrogate threshold effect
      (STE) and the Biomarker-Surrogacy (BioSurrogate) Evaluation Schema (BSES).
AB  - BACKGROUND: Blood pressure is considered to be a leading example of a valid
      surrogate endpoint. The aims of this study were to (i) formally evaluate systolic
      and diastolic blood pressure reduction as a surrogate endpoint for stroke
      prevention and (ii) determine what blood pressure reduction would predict a
      stroke benefit. METHODS: We identified randomised trials of at least six months
      duration comparing any pharmacologic anti-hypertensive treatment to placebo or no
      treatment, and reporting baseline blood pressure, on-trial blood pressure, and
      fatal and non-fatal stroke. Trials with fewer than five strokes in at least one
      arm were excluded. Errors-in-variables weighted least squares regression modelled
      the reduction in stroke as a function of systolic blood pressure reduction and
      diastolic blood pressure reduction respectively. The lower 95% prediction band
      was used to determine the minimum systolic blood pressure and diastolic blood
      pressure difference, the surrogate threshold effect (STE), below which there
      would be no predicted stroke benefit. The STE was used to generate the surrogate
      threshold effect proportion (STEP), a surrogacy metric, which with the R-squared
      trial-level association was used to evaluate blood pressure as a surrogate
      endpoint for stroke using the Biomarker-Surrogacy Evaluation Schema (BSES3).
      RESULTS: In 18 qualifying trials representing all pharmacologic drug classes of
      antihypertensives, assuming a reliability coefficient of 0.9, the surrogate
      threshold effect for a stroke benefit was 7.1 mmHg for systolic blood pressure
      and 2.4 mmHg for diastolic blood pressure. The trial-level association was 0.41
      and 0.64 and the STEP was 66% and 78% for systolic and diastolic blood pressure
      respectively. The STE and STEP were more robust to measurement error in the
      independent variable than R-squared trial-level associations. Using the BSES3,
      assuming a reliability coefficient of 0.9, systolic blood pressure was a B +
      grade and diastolic blood pressure was an A grade surrogate endpoint for stroke
      prevention. In comparison, using the same stroke data sets, no STEs could be
      estimated for cardiovascular (CV) mortality or all-cause mortality reduction,
      although the STE for CV mortality approached 25 mmHg for systolic blood pressure.
      CONCLUSIONS: In this report we provide the first surrogate threshold effect (STE)
      values for systolic and diastolic blood pressure. We suggest the STEs have face
      and content validity, evidenced by the inclusivity of trial populations, subject
      populations and pharmacologic intervention populations in their calculation. We
      propose that the STE and STEP metrics offer another method of evaluating the
      evidence supporting surrogate endpoints. We demonstrate how surrogacy evaluations
      are strengthened if formally evaluated within specific-context evaluation
      frameworks using the Biomarker- Surrogate Evaluation Schema (BSES3), and we
      discuss the implications of our evaluation of blood pressure on other biomarkers
      and patient-reported instruments in relation to surrogacy metrics and trial
      design.

PMID- 22409775
TI  - Family medicine in post-communist Europe needs a boost. Exploring the position of
      family medicine in healthcare systems of Central and Eastern Europe and Russia.
AB  - BACKGROUND: The countries of Central and Eastern Europe have experienced a lot of
      changes at the end of the 20th century, including changes in the health care
      systems and especially in primary care. The aim of this paper is to
      systematically assess the position of family medicine in these countries, using
      the same methodology within all the countries. METHODS: A key informants survey
      in 11 Central and Eastern European countries and Russia using a questionnaire
      developed on the basis of systematic literature review. RESULTS: Formally, family
      medicine is accepted as a specialty in all the countries, although the levels of
      its implementation vary across the countries and the differences are important.
      In most countries, solo practice is the most predominant organisational form of
      family medicine. Family medicine is just one of many medical specialties (e.g.
      paediatrics and gynaecology) in primary health care. Full introduction of family
      medicine was successful only in Estonia. CONCLUSIONS: Some of the unification of
      the systems may have been the result of the EU request for adequate training that
      has pushed the policies towards higher standards of training for family medicine.
      The initial enthusiasm of implementing family medicine has decreased because
      there was no initiative that would support this movement. Internal and external
      stimuli might be needed to continue transition process.

PMID- 22409776
TI  - Effects of atopy and rhinitis on exhaled nitric oxide values - a systematic
      review.
AB  - BACKGROUND: Atopy and rhinitis are among the factors affecting exhaled nitric
      oxide (FeNO) values and may contribute to difficulties in the clinical
      interpretation of FeNO measurements. However, data assessing their effects on
      FeNO values had never been summarized. This review aims to evaluate the effect of
      atopy and rhinitis in FeNO values in otherwise healthy individuals. METHODS: A
      systematic review was performed in Pubmed, Scopus and ISI Web of Knowledge. A two
      step selection process was completed, and from 2357 references 19 were included.
      The inclusion criteria were: participants without known diseases other than
      rhinitis; atopy assessement by SPT or Specific IgE; and FeNO measurements
      according to ATS/ERS recommendations. RESULTS: The 8 articles measuring FeNO in
      children showed higher values in both allergic rhinitis and atopic children when
      compared with healthy children. The 11 articles performed in adults observed
      higher FeNO in AR patients comparatively with either healthy or atopic
      individuals. However, adult healthy and atopic individuals had similar FeNO
      values. CONCLUSIONS: FeNO values are higher in individuals with rhinitis and/or
      atopy without other health problems. These effects are small, seem to be
      independent and should be further studied using multivariate models. The effect
      of atopy was observed only in children. The combined effect of atopy and rhinitis
      produced higher FeNO values in adults. These results support that both atopy and
      rhinitis should be considered when interpreting or when defining FeNO reference
      values.

PMID- 22409778
TI  - The relative effect of surface strontium chemistry and super-hydrophilicity on
      the early osseointegration of moderately rough titanium surface in the rabbit
      femur.
AB  - OBJECTIVE: It is unclear whether surface bioactive chemistry or hydrophilicity
      plays a more dominant role in the osseointegration of micro-structured titanium
      implants having the same surface topography at the micrometer and submicrometer
      scales. To understand their comparative effect on enhancing the early
      osseointegration of micro-rough-surfaced implants, this study compared the bone
      healing-promoting effect of surface strontium (Sr) chemistry that has been shown
      in numerous studies to super-hydrophilicity in the early osseointegration of
      moderately rough-surfaced clinical oral implants (SLA((r)) implant) in rabbit
      cancellous bone. MATERIAL AND METHODS: Hydrothermal treatment was performed to
      incorporate Sr ions into the surface of clinical SLA implants (SLA/Sr implant).
      The surface characteristics were evaluated by using field emission-scanning
      electron microscopy, X-ray photoelectron spectroscopy and optical profilometry.
      Twenty screw implants (10 control and 10 experimental) were placed in the femoral
      condyles of 10 New Zealand White rabbits. The early osseointegration of the
      SLA/Sr implant was compared with a chemically modified super-hydrophilic SLA
      implant (SLActive((r)) implant) by histomorphometric and resonance frequency
      analysis after 2 weeks of implantation. RESULTS: The SLA/Sr and SLActive implants
      exhibited an identical surface topography and average R(a) values at the micron
      and submicron scales. The SLA/Sr implant displayed a high amount of surface Sr
      content (15.6 at.%). There was no significant difference in the implant stability
      quotient (ISQ) values between the two groups. However, histomorphometric analysis
      revealed a significantly higher bone-to-implant contact percentage in the SLA/Sr
      implants compared with the SLActive implants in rabbit cancellous bone (P <
      0.01). CONCLUSION: The results indicate that the surface Sr chemistry surpasses
      the effect of super-hydrophilicity in promoting the early bone apposition of
      moderately rough Ti surface in cancellous bone.

PMID- 22409777
TI  - Diabetes and oral disease: implications for health professionals.
AB  - "Diabetes and Oral Disease: Implications for Health Professionals" was a one-day
      conference convened by the Columbia University College of Dental Medicine, the
      Columbia University College of Physicians and Surgeons, and the New York Academy
      of Sciences on May 4, 2011 in New York City. The program included an examination
      of the bidirectional relationship between oral disease and diabetes and the
      interprofessional working relationships for the care of people who have diabetes.
      The overall goal of the conference was to promote discussion among the healthcare
      professions who treat people with diabetes, encourage improved communication and
      collaboration among them, and, ultimately, improve patient management of the oral
      and overall effects of diabetes. Attracting over 150 members of the medical and
      dental professions from eight different countries, the conference included
      speakers from academia and government and was divided into four sessions. This
      report summarizes the scientific presentations of the event.

PMID- 22409779
TI  - Clinical significance of infections caused by extended-spectrum beta-lactamase
      producing Enterobacteriaceae blood isolates with inducible AmpC beta-lactamase.
AB  - Few studies have investigated the clinical features and outcomes for extended
      spectrum beta-lactamase (ESBL)-producing Enterobacter spp., Citrobacter spp.,
      Serratia spp., and Morganella morganii (ECSM) bloodstream infections. This study
      was performed to investigate the clinical features and outcomes for ESBL
      producing ECSM bloodstream infections. Patients with ECSM bloodstream infection
      were enrolled from October 2006 to March 2008. Of 124 patients with ECSM
      bacteremia, 30 cases (24.2%) were ESBL-producing isolates. Immunosuppressive
      drugs use within 30 days (p=0.028), indwelling device at the time of bacteremia
      (p=0.042) and antibiotics use within 3 months (p=0.022) were independently
      associated with ESBL production in multivariate analysis. Overall 30-day
      mortality rate was 19.4% (24/124). When the 30-day mortality rate was evaluated,
      no significant difference was found between the ESBL group (16.6%; 5/30) and non
      ESBL group (20.2%; 19/94). Hospitalization was longer in the ESBL group than in
      the non-ESBL group (65.4+/-92.8 vs. 32.9+/-37.8 days, respectively; p=0.007). The
      recent use of antibiotics (especially broad-spectrum cephalosporins and other
      beta-lactam antibiotics) was an important risk factor for ESBL among ECSM
      bacteremia. ESBL production of ECSM isolates was not significantly associated
      with mortality but ESBL-producing organisms have an important impact on the
      duration of hospital stay and subsequent medical cost.

PMID- 22409781
TI  - Editorial: Meeting the health care needs associated with poverty, homelessness
      and social exclusion: the need for an interprofessional approach.

PMID- 22409780
TI  - Reverse iontophoresis of urea in health and chronic kidney disease: a potential
      diagnostic and monitoring tool?
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) need regular monitoring,
      usually by blood urea and creatinine measurements, needing venepuncture, frequent
      attendances and a healthcare professional, with significant inconvenience.
      Noninvasive monitoring will potentially simplify and improve monitoring. We
      tested the potential of transdermal reverse iontophoresis of urea in patients
      with CKD and healthy controls. METHODS: Using a MIC 2((r)) Iontophoresis
      Controller, reverse iontophoresis was applied on the forearm of five healthy
      subjects (controls) and 18 patients with CKD for 3-5 h. Urea extracted at the
      cathode was measured and compared with plasma urea. RESULTS: Reverse
      iontophoresis at 250 MUA was entirely safe for the duration. Cathodal buffer urea
      linearly correlated with plasma urea after 2 h (r = 0.82, P < 0.0001), to 3.5 h
      current application (r = 0.89, P = 0.007). The linear equations y = 0.24x + 1 and
      y = 0.21x + 4.63 predicted plasma urea (y) from cathodal urea after 2 and 3 h,
      respectively. Cathodal urea concentration in controls was significantly lower
      than in patients with CKD after a minimum current application of 2 h (P <
      0.0001), with the separation between the two groups becoming more apparent with
      longer application (P = 0.003). A cathodal urea cut-off of 30 MUM gave a
      sensitivity of 83.3% and positive predictive value of 87% CKD. During
      haemodialysis, the fall in cathodal urea was able to track that of blood urea.
      CONCLUSION: Reverse iontophoresis is safe, can potentially discriminate patients
      with CKD and healthy subjects and is able to track blood urea changes on
      dialysis. Further development of the technology for routine use can lead to an
      exciting opportunity for its use in diagnostics and monitoring.

PMID- 22409782
TI  - Influence of exercise on mood in postmenopausal women.
AB  - AIM AND OBJECTIVE: To evaluate the influence of an exercise programme on
      postmenopausal women with symptoms of anxiety and depression. BACKGROUND: The
      menopause is a period of hormonal changes when mood variations are probably more
      severe than at any other period of women's lives. DESIGN: Prospective study with
      control group and pre- and post-treatment measures, after six months treatment.
      Conducted at two healthcare clinics, in the province of Granada (Spain). METHODS:
      A convenience sample of 60 postmenopausal women aged 60-70 years, with symptoms
      of depression and anxiety, was recruited. The women were randomly divided into
      two groups: (1) control group, no treatment (n = 30); (2) exercise group, which
      carried out a programme of mixed physical exercises with musical support (n =
      30). All subjects answered questionnaires for the Hamilton Anxiety Scale and the
      Brink and Yesavage Geriatric Depression Scale before and after treatment.
      RESULTS: In the exercise group, statistically significant improvements were
      observed in subjects with moderate and severe depression (18 and 22%,
      respectively) and in those with symptoms of anxiety. No such changes were
      observed in the control group. CONCLUSIONS: A controlled programme of physical
      exercise for postmenopausal women alleviates symptoms of anxiety and depression,
      and its inclusion in primary healthcare programmes should be considered.
      RELEVANCE TO CLINICAL PRACTICE: Menopausal women may benefit from physical
      exercise, which attenuates the effects of the physiological and psychological
      changes associated with the menopause and prevents pathologic changes.

PMID- 22409783
TI  - Commentary on Kwong E, Lau A, Lee R & Kwan R (2011) A pressure ulcer prevention
      programme specially designed for nursing homes: does it work? Journal of Clinical
      Nursing 20, 2777-2786.

PMID- 22409784
TI  - Response to Moore Z & Cowman S (2012) Pressure ulcer prevalence and prevention
      practices in care of the older person in the Republic of Ireland, Journal of
      Clinical Nursing 21, 362-371.

PMID- 22409785
TI  - Response to Sasso L (2011) Commentary on Thompson DR & Watson R (2010) Guest
      editorial: h-indexes and the performance of nursing professors of nursing in the
      UK. Journal of Clinical Nursing 19, 2957-2958. Journal of Clinical Nursing 20,
      2685-2686.

PMID- 22409787
TI  - Comparison of the cytotoxic response against ovarian cancer by immune effector
      cells isolated and expanded from normal donors and ovarian cancer patients.
AB  - BACKGROUND/AIMS: The aim of this study was to compare the cytotoxic response
      against ovarian cancer (OC) cells elicited by different immune effector cells in
      combination with the cytokines interleukin (IL)-2 and interferon (IFN) alpha-2b.
      METHODS: OC cells were co-cultured with peripheral blood mononuclear cells (PBMC)
      from normal donors or OC patients and IL-2 or IFN alpha-2b alone or in
      combination, in order to determine the cytotoxicity. T cells were isolated from
      healthy donors to determine T cell cytotoxic activity. PBMC from healthy donors
      and OC patients were expanded in an IL-2/IL-7/IL-12 cocktail with and without
      anti-CD3 antibody, and the cytotoxic activity measured. Flow cytometry was
      performed on primary, selected and expanded cells to determine T, B, and natural
      killer- (NK) cell percentages. RESULTS: Healthy donor PBMC elicited a significant
      cytotoxic response (59%) compared with OC patient PBMC (7%). T cells enriched
      from normal donors elicited a significant cytotoxic response (18%) compared with
      controls lacking effector cells (1.4%); however, the cytotoxicity observed was
      significantly less compared with unselected PBMC. Expanded effector cells
      consisted primarily of T cells (98%) and the fold-expansion was significantly
      higher in the presence of anti-CD3 (19- versus 132-fold). No significant
      difference in the expansion (either fold-expansion or cell type) was observed
      between OC patients and healthy donors. Expanded cells from both healthy donors
      and OC patients elicited a significant cytotoxic response in the presence of IL-2
      (19% and 22%) compared with controls. CONCLUSIONS: PBMC from OC patients do not
      elicit a significant cytotoxic response; however, ex vivo-expanded cells from OC
      patients are capable of cytotoxic killing similar to unexpanded T cells isolated
      from normal donors. These data provide the groundwork for further development of
      cellular therapy against OC.

PMID- 22409790
TI  - Perioperative transoesophageal echocardiography: past, present & future.

PMID- 22409789
TI  - Long-term treatment outcomes of ritonavir-boosted lopinavir monotherapy among HIV
      infected patients who experienced NRTI and NNRTI failure.
AB  - BACKGROUND: We continue the previously described prospective cohort study of
      ritonovir-boosted lopinavir (LPV/r) monotherapy for second-line therapy in HIV
      infected patients with prior failure and extensive resistance to nucleoside
      reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase
      inhibitors (NNRTIs), with the objective being to determine the three-year
      treatment responses. FINDINGS: There were 40 patients with a mean +/- SD age of
      37 +/- 8 years. Median (IQR) baseline CD4 was 123 (37-245) cells/mm3 and median
      (IQR) HIV-1 RNA was 55,800 (9,670-100,000) copies/mL. All patients received twice
      daily LPV/r 400/100 mg and recycled lamivudine 150 mg. By intend-to-treat
      analysis at 144 weeks, 26 (65%) and 22 (56%) patients achieved HIV-1 RNA at < 400
      and < 50 copies/mL, respectively. In as-treated analysis, the corresponding rates
      were 26 of 28 (93%) and 22 of 28 (78%), respectively. Low-level viral rebound
      (HIV-1 RNA 50-400 copies/mL) was found in 6 (15%), 6 (15%), and 4 (10%) patients
      at week 48, 96 and week 144, respectively. Medians CD4 at week 48, 96, and 144
      were 351, 481, and 584 cells/mm3 and significantly changed from baseline (all, P
      < 0.05). There were increments of mean triglycerides at 48 weeks and 144 weeks
      from baseline (P < 0.05). No major protease resistance-associated mutations
      emerged after virologic failure. CONCLUSION: LPV/r monotherapy with recycled
      lamivudine can maintain long-term virologic suppression in a relatively small
      proportion of patients failing NNRTI-based regimen and having limit option for
      active NRTI. More antiretroviral classes are needed be accessible in resource
      limited countries.

PMID- 22409791
TI  - Limiting the dose of local anaesthetic for caesarean section under spinal
      anaesthesia--has the limbo bar been set too low?

PMID- 22409788
TI  - Engaging HIV-HCV co-infected patients in HCV treatment: the roles played by the
      prescribing physician and patients' beliefs (ANRS CO13 HEPAVIH cohort, France).
AB  - BACKGROUND: Treatment for the hepatitis C virus (HCV) may be delayed
      significantly in HIV/HCV co-infected patients. Our study aims at identifying the
      correlates of access to HCV treatment in this population. METHODS: We used 3-year
      follow-up data from the HEPAVIH ANRS-CO13 nationwide French cohort which enrolled
      patients living with HIV and HCV. We included pegylated interferon and ribavirin
      naive patients (N = 600) at enrolment. Clinical/biological data were retrieved
      from medical records. Self-administered questionnaires were used for both
      physicians and their patients to collect data about experience and behaviors,
      respectively. RESULTS: Median [IQR] follow-up was 12[12-24] months and 124
      patients (20.7%) had started HCV treatment. After multiple adjustment including
      patients' negative beliefs about HCV treatment, those followed up by a general
      practitioner working in a hospital setting were more likely to receive HCV
      treatment (OR[95%CI]: 1.71 [1.06-2.75]). Patients followed by general
      practitioners also reported significantly higher levels of alcohol use, severe
      depressive symptoms and poor social conditions than those followed up by other
      physicians. CONCLUSIONS: Hospital-general practitioner networks can play a
      crucial role in engaging patients who are the most vulnerable and in reducing
      existing inequities in access to HCV care. Further operational research is needed
      to assess to what extent these models can be implemented in other settings and
      for patients who bear the burden of multiple co-morbidities.

PMID- 22409792
TI  - EVAR fever: minimally invasive, maximally inclusive?

PMID- 22409793
TI  - An investigation into the causes of unexpected intra-operative transoesophageal
      echocardiography findings.
AB  - There is uncertainty regarding echocardiography before cardiac surgery,
      especially with regard to timing and disease progression as well as potential
      errors. We investigated the causes of unexpected intra-operative transoesophageal
      echocardiography findings by performing a 33-month audit. We found that there
      were 50/797 (6%) unexpected findings that led to an alteration in surgical
      strategy in 34 (4%) patients. Of the unexpected findings, 25 (50%) were unrelated
      to pre-operative pathology. After reviewing pre-operative studies and reports,
      unexpected findings were found to be due to: reporting errors in 20 patients
      (44%); limitations in transthoracic compared to transoesophageal echocardiography
      in 14 patients (30%); disease progression in 10 patients (22%); and inter
      observer variability in two patients (4%). We identified six reports out of 797
      (0.8%) that contained potentially serious errors. Surgical management changed in
      18/20 (90%) patients in whom the unexpected change was due to reporting error,
      compared to 16/30 (53%) patients whose pre-operative echocardiogram was correctly
      reported (p = 0.006). Our study suggests that pre-operative echocardiography
      reporting errors are common and important.

PMID- 22409794
TI  - An alternative to a shoulder roll for infants.

PMID- 22409795
TI  - Oesophageal Doppler monitoring: evidence and hip surgery.

PMID- 22409796
TI  - Oesophageal Doppler monitoring: premature guidance and what about the fluids?

PMID- 22409797
TI  - Oesophageal Doppler monitoring: costly and supported by weak evidence.

PMID- 22409798
TI  - Oesophageal Doppler monitoring: a misguided editorial.

PMID- 22409799
TI  - Oesophageal Doppler monitoring: a not-so-NICE editorial.

PMID- 22409800
TI  - Oesophageal Doppler monitoring: the role of NICE.

PMID- 22409802
TI  - An ADEPT apology.

PMID- 22409804
TI  - Cardiovascular intubation responses with Airway Scope and Macintosh laryngoscope.

PMID- 22409806
TI  - Airtraq insertion requires dexterity.

PMID- 22409807
TI  - Logging the delivery of intravenous lipid emulsion for cocaine and other
      lipophilic drug overdoses.

PMID- 22409808
TI  - Care is never withdrawn.

PMID- 22409809
TI  - Smartphones, Twitter and new learning opportunities at anaesthetic conferences.

PMID- 22409811
TI  - Intracortical injection of endothelin-1 induces cortical infarcts in mice: effect
      of neuronal expression of an adenosine transporter.
AB  - BACKGROUND: Activation of adenosine A1 receptors has neuroprotective effects in
      animal stroke models. Adenosine levels are regulated by nucleoside transporters.
      In vitro studies showed that neuron-specific expression of human equilibrative
      nucleoside transporter 1 (hENT1) decreases extracellular adenosine levels and
      adenosine A1 receptor activity. In this study, we tested the effect of hENT1
      expression on cortical infarct size following intracerebral injection of the
      vasoconstrictor endothelin-1 (ET-1) or saline. METHODS: Mice underwent
      stereotaxic intracortical injection of ET-1 (1 MUl; 400 pmol) or saline (1 MUl).
      Some mice received the adenosine receptor antagonist caffeine (25 mg/kg,
      intraperitoneal) 30 minutes prior to ET-1. Perfusion and T2-weighted magnetic
      resonance imaging (MRI) were used to measure cerebral blood flow (CBF) and
      subsequent infarct size, respectively. RESULTS: ET-1 reduced CBF at the injection
      site to 7.3 +/- 1.3% (n = 12) in hENT1 transgenic (Tg) and 12.5 +/- 2.0% (n = 13)
      in wild type (Wt) mice. At 48 hours following ET-1 injection, CBF was partially
      restored to 35.8 +/- 4.5% in Tg and to 45.2 +/- 6.3% in Wt mice; infarct sizes
      were significantly greater in Tg (9 +/- 1.1 mm3) than Wt (5.4 +/- 0.8 mm3) mice.
      Saline-treated Tg and Wt mice had modest decreases in CBF and infarcts were less
      than 1 mm3. For mice treated with caffeine, CBF values and infarct sizes were not
      significantly different between Tg and Wt mice. CONCLUSIONS: ET-1 produced
      greater ischemic injury in hENT1 Tg than in Wt mice. This genotype difference was
      not observed in mice that had received caffeine. These data indicate that hENT1
      Tg mice have reduced ischemia-evoked increases in adenosine receptor activity
      compared to Wt mice.

PMID- 22409812
TI  - Information flow in interaction networks II: channels, path lengths, and
      potentials.
AB  - In our previous publication, a framework for information flow in interaction
      networks based on random walks with damping was formulated with two fundamental
      modes: emitting and absorbing. While many other network analysis methods based on
      random walks or equivalent notions have been developed before and after our
      earlier work, one can show that they can all be mapped to one of the two modes.
      In addition to these two fundamental modes, a major strength of our earlier
      formalism was its accommodation of context-specific directed information flow
      that yielded plausible and meaningful biological interpretation of protein
      functions and pathways. However, the directed flow from origins to destinations
      was induced via a potential function that was heuristic. Here, with a
      theoretically sound approach called the channel mode, we extend our earlier work
      for directed information flow. This is achieved by constructing a potential
      function facilitating a purely probabilistic interpretation of the channel mode.
      For each network node, the channel mode combines the solutions of emitting and
      absorbing modes in the same context, producing what we call a channel tensor. The
      entries of the channel tensor at each node can be interpreted as the amount of
      flow passing through that node from an origin to a destination. Similarly to our
      earlier model, the channel mode encompasses damping as a free parameter that
      controls the locality of information flow. Through examples involving the yeast
      pheromone response pathway, we illustrate the versatility and stability of our
      new framework.

PMID- 22409813
TI  - Ion mobility mass spectrometry coupled with rapid protein threading predictor
      structure prediction and collision-induced dissociation for probing chemokine
      conformation and stability.
AB  - Unique to ion mobility mass spectrometry (IM-MS) is the ability to provide
      collision cross section (CCS) data and the capacity to delineate any dissociation
      and/or unfolding of protein complexes. The strong correlation of the
      experimentally determined CCS with theory is indicative of the retention of
      native structure in the gas phase, which in turn, qualifies as a means in
      evaluating the IM-MS data. The assessment of IM-MS data, however, is currently
      impeded due to the lack of appropriate structural coordinates to use as input in
      the in silico calculation of theory. To address this issue, this study involves
      the use of rapid protein threading predictor (RAPTOR) to generate tertiary
      structures of closely related monomeric chemokines (MCP-1, MCP-3, MCP-4, and
      eotaxin) and, subsequently, utilize these models to estimate the theoretical
      values. Experimental CCS of both the model proteins and chemokines correlate well
      with theory generated by RAPTOR. All conformations for z = 5+ of chemokines fall
      within theoretical limits. Of the four chemokines, MCP-4 with z = 6+ appears to
      adopt an extended conformation, while eotaxin gradually unfolds, and the extended
      structures of MCP-1 and MCP-3 increase in abundance upon activation. Combining
      RAPTOR with IM-MS and collision-induced dissociation (CID) enables us to
      interrogate the conformations of homologous proteins with very similar tertiary
      structures.

PMID- 22409814
TI  - Ultrasound imaging for the rheumatologist XXXVII. Sonographic assessment of the
      hip in ankylosing spondylitis patients.
AB  - OBJECTIVES: To investigate the prevalence of ultrasound (US) detectable
      inflammation in hips of patients with ankylosing spondylitis (AS) and the
      relationship between US and measures of disease activity and severity. METHODS:
      Consecutive patients with AS attending the rheumatology units involved in this
      study were enrolled. Clinical and demographical data were recorded. US
      examination of bilateral hips was performed at the same time, evaluating anterior
      longitudinal scan to search for synovial hypertrophy (SH), joint effusion (JE) or
      power Doppler (PD) positive synovitis. RESULTS: A total of 56 patients were
      included, median age (interquartile range, IQR) 49 (39, 59.5), median disease
      duration 98 (72, 204) months, 80.3% were treated with TNF-alpha inhibitors,
      median BASDAI 2.65 (1.96, 3.95), 30.3% had hip tenderness. US JE was found in
      26.7% of patients, US SH in 16%, no patient had detectable PD. The concordance
      between clinical findings and US abnormalities was moderate, with a kappa of
      0.44. Patients with detectable US abnormalities had higher median visual analogue
      scale (VAS) pain and C-reactive protein (CRP), while there was no significant
      association with other measures of disease activity and disability. In the
      subgroup of patients with no hip tenderness, US alterations were still
      significantly related to higher CRP levels, while in patients with hip tenderness
      and no US abnormalities CRP was not higher than in the asymptomatic patients.
      CONCLUSIONS: US assessment of hip joint in AS patients can be considered of
      value, as suggested by the correlation with relevant clinical and laboratory
      measures. In asymptomatic patients, US examination might provide further
      information on subclinical involvement.

PMID- 22409816
TI  - Integration of HIV testing in tuberculosis drug resistance surveillance in
      Kazakhstan and Kenya.
AB  - In Kenya and Kazakhstan, integration of human immunodeficiency virus (HIV)
      testing results into the routine surveillance of multidrug-resistant tuberculosis
      (MDR-TB) proved feasible and useful. The integration process improved overall
      data quality and data validation capacity, and integrated  data are a useful
      addition to routine cohort and treatment outcome data. Besides their importance
      for individual patient care, they provide trends on the association of MDR-TB and
      HIV in the routine programme setting. They also form a useful epidemiological
      basis for more specific studies,  such as on nosocomial outbreaks. Whether the
      system itself is sensitive enough to monitor possible outbreaks needs further
      investigation.

PMID- 22409817
TI  - Different incidences of epigenetic but not genetic abnormalities between Wilms
      tumors in Japanese and Caucasian children.
AB  - Epidemiological studies show that the incidence of Wilms tumor (WT) in East-Asian
      children is half of that in Caucasian children. Abnormalities of WT1, CTNNB1,
      WTX, and IGF2 were reported to be involved in Wilms tumorigenesis in Caucasians,
      although none of the studies simultaneously evaluated the four genes. WTX forms
      the beta-catenin degradation complex; however, the relationship between WTX
      abnormality and CTNNB1 mutation was uncertain in WTs. We examined abnormalities
      of the four genes in 114 Japanese with WTs to clarify the relationship between
      genetic and epigenetic factors and the incidence of WTs. We found that
      abnormalities of WTX and CTNNB1 were mutually exclusive, and that although CTNNB1
      mutation was frequent in WTs with WT1 abnormality, but rare in WTs without, the
      incidences of WTX abnormality were similar between WTs with or without WT1
      abnormality. These findings were consistent with those reported in Caucasian
      populations, and indicate multiple roles of WTX abnormality. Abnormalities of
      WT1, WTX and CTNNB1, and loss of IGF2 imprinting (LOI) were detected in 31.6%,
      22.8%, 26.3%, and 21.1% of the 114 WTs, respectively. When we selected 101
      sporadic WTs, the incidences of WT1, CTNNB1, or WTX abnormality were generally
      comparable between the two populations, whereas the incidence of IGF2 LOI was
      lower in Japanese than that of IGF2 LOI reported in Caucasians (P = 0.04). This
      is the first comprehensive study of the four genes, and the results supported the
      hypothesis that the lower incidence of IGF2 LOI contributes to the lower
      incidence of WTs in Japanese children.

PMID- 22409818
TI  - Preface.

PMID- 22409819
TI  - New insights into the biology of molecular subtypes of diffuse large B-cell
      lymphoma and Burkitt lymphoma.
AB  - Diffuse large B-cell lymphoma and Burkitt lymphoma are two distinct lymphoma
      entities recognized by the current World Health Organization classification of
      lymphoid neoplasms. Although diagnostic criteria to distinguish these two
      subtypes have been established, a subset of cases have overlapping
      characteristics and therefore, the distinction can be challenging. Thus, the
      World Health Organization classification introduced an intermediate subtype
      referred as "B-cell lymphoma, unclassifiable, with features intermediate between
      diffuse large B-cell lymphoma and Burkitt lymphoma". This review summarizes our
      current understanding of the biology of these lymphoma subtypes.

PMID- 22409820
TI  - New biomarkers in T-cell lymphomas.
AB  - Peripheral T-cell lymphomas (PTCLs) are heterogeneous and uncommon malignancies
      characterized by an aggressive clinical course and a mostly poor outcome with
      current treatment strategies. The recent genome-wide molecular characterization
      of several entities has provided novel insights into their pathobiology and led
      to the identification of new biomarkers with diagnostic, prognostic or
      therapeutic implications for PTCL patients. Cell lineage and differentiation
      antigens (markers of gammadelta or NK lineage, of cytotoxicity, of follicular
      helper T cells) reflect the tumour's biological behaviour, and their detection in
      tissue samples may refine the diagnostic and prognostic stratification of the
      patients. Previously unrecognized gene rearrangements are being discovered (ITK
      SYK translocation, IRF4/MUM1 and DUSP22 rearrangements), and may serve as
      diagnostic genetic markers. Deregulated molecules within oncogenic pathways (NF
      kappaB, Syk, PDGFRalpha) and immunoreactive cell-surface antigens (CD30, CD52)
      have been brought to the fore as potential targets for guiding the development of
      novel therapies.

PMID- 22409821
TI  - Image-guided needle biopsy for diagnosis and molecular biology in lymphomas.
AB  - Core needle biopsy is increasingly replacing excisional lymph node biopsy in the
      diagnosis and subclassification of malignant lymphomas, with obvious advantages
      in terms of morbidity and costs. This technique has radically altered the
      diagnostic strategy of enlarged lymph nodes at our institution, avoiding
      unnecessary nodal excisions. It represents a viable alternative as long as the
      number and size of cores for morphologic and molecular studies are not
      compromised. This quick and safe technique can be applied to the initial
      diagnostic evaluation of malignant lymphomas as well as the reassessment of
      previously diagnosed malignant lymphomas at time of progression or recurrence.

PMID- 22409822
TI  - Diffuse large B cell lymphoma: how can we cure more patients in 2012?
AB  - Clinically this chapter will focus on 3 important issues critical in the
      management of diffuse large B cell lymphoma (DLBCL) in 2012: risk stratification,
      interim PET-CT scanning and the role of high dose therapy and ASCT in the
      rituximab era for patients with relapsed and primary refractory disease.

PMID- 22409823
TI  - Relapses, treatments and new drugs.
AB  - We now better understand that the treatment of Diffuse Large B-cell lymphoma
      (DLBCL) must take into account individual factors related to the biological
      characteristics of tumors and patients. Treatment failure has dramatically
      reduced with the combination of rituximab and chemotherapy, mostly in the
      germinal center B (GCB) cell-like subset. However, salvage chemotherapy and
      autotransplantation are less effective in patients with previous exposure to
      rituximab. Therefore, new therapies should focus on poor-risk patients or on the
      non-CG subset. After reviewing the recent data on salvage strategy, we aimed to
      focus on novel agents that have been shown to be promising for future therapy of
      DLBCL (e.g., monoclonal antibody-based therapy and small-molecule inhibitors)
      and, lastly, to present perspectives on the use of these new agents in
      combination.

PMID- 22409824
TI  - Autologous or allogeneic transplantation in B- and T-cell lymphomas.
AB  - The roles of HDT/autoSCT and alloSCT in the treatment of B- and T-cell lymphomas
      continue to change. With the wider use of Rituximab in virtually every patient
      with B-cell lymphoma transplantation as part of first-line therapy has been
      challenged. New studies fail to show a benefit of HDT/autoSCT over conventional
      therapy when administered to newly diagnosed patients with aggressive B-cell
      lymphoma; in the other B-cell lymphomas results from randomized studies are not
      yet available. Patients relapsing from first-line therapy including Rituximab do
      not have satisfying results with HDT/autoSCT. Therefore, alloSCT is increasingly
      being considered. In T-cell lymphoma the efficacy of autoSCT seems rather
      limited. Study groups and single institutions are developing new strategies
      including alloSCT to improve the situation for such patients both in the setting
      of first-line and salvage therapy.

PMID- 22409826
TI  - Therapeutic strategies in elderly and very elderly patients.
AB  - Management of the elderly with lymphoma needs specific attention. This means
      supplementary evaluation as regards to younger patients. The objective is to
      identify specific weaknesses of the patients and thus to foresee potential
      unexpected toxicities which may endanger patients' outcome. With this
      information, the hematologist will be able to propose an optimized treatment
      strategy i.e. with an adapted efficacy/toxicity ratio. These general principles
      are consensual but it remains to determine what the practical content of this
      approach is. Recent results suggest some specific tools for the pre-treatment
      evaluation. Some specific indexes have been proposed to categorize patients but
      the ultimate approach remains to be outlined. Finally, while geriatric
      intervention has demonstrated its capacity to improve survival in the general
      elderly population, no such demonstration has been made in cancer patients
      including lymphoma.

PMID- 22409825
TI  - EBV-associated lymphomas in adults.
AB  - Epstein-Barr virus (EBV) is a ubiquitous gamma-herpes virus that infects most
      people but results in life-threatening diseases in only a small subset. Persons
      who are unable to maintain the virus in its latent state can develop uncontrolled
      EBV-driven lymphoproliferative disorders and lymphomas. EBV-associated lymphomas
      are well characterized in patients with known defects in cellular immunity as
      occurs post-transplantation or HIV/AIDS but are increasingly recognized in
      patients without overt immunodeficiencies. Improved understanding of the biology
      of these lymphomas and the role EBV plays in lymphomagenesis offer the
      opportunity for improved therapies targeted at important signaling pathways and
      immunotherapy specific against EBV viral antigens.

PMID- 22409827
TI  - HIV-associated lymphoma.
AB  - The incidence of aggressive lymphoma in the setting of HIV infection is
      significantly increased relative to the general population. Combination
      antiretroviral therapy (cART) for HIV has reduced the incidence of these
      neoplasms and has significantly improved clinical outcome for those who do
      develop lymphoma and require chemotherapy. With the possible exception of those
      individuals with the most severe immunocompromise, patients with HIV-associated
      lymphoma can be treated with the same standard immuno-chemotherapy regimens used
      in the immunocompetent population with similar expectations for good clinical
      outcome. Infusional regimens like dose adjusted EPOCH-R appear to be highly
      effective first-line therapy and for relapsed patients high-dose chemotherapy
      with autologous stem cell support is well-tolerated and effective. However, it
      should be recognized that there are unique risks associated with management of
      lymphoma in this patient population. While opportunistic infections are no longer
      a significant cause of death, antiretroviral agents used for management of HIV
      infection may interact with chemotherapeutic agents and other adjunctive
      therapies making communication between the treating Oncologist and the patient's
      primary HIV treatment provider of prime importance.

PMID- 22409828
TI  - Primary CNS lymphoma.
AB  - Primary CNS lymphoma (PCNSL) is a rare and aggressive brain tumor with an
      unsatisfactory outcome. Therapeutic progress in this field is strongly
      conditioned by the limited biology and the molecular knowledge about this
      disease, which hamperizes the identification of new targeted therapies and the
      poor clinical conditions and performance status of patients, rendering very
      difficult their enrollment in prospective trials. Chemoradiation therapy is the
      most commonly used strategy for patients with PCNSL, which is associated with
      better efficacy rates, but also with high incidence of severe neurotoxicity. As a
      consequence, a dilemma in PCNSL treatment is the choice between strategies
      designed to intensify therapy to improve the cure rate, versus strategies of
      treatment de-escalation to avoid severe neurotoxicity. The efficacy of
      chemotherapy is strongly limited by the special functional and microenvironmental
      characteristics of the CNS, which is variably protected by the blood-brain
      barrier (BBB) and includes extensive chemotherapy sanctuaries where tumor cells
      grow undisturbed. Drugs exhibiting a good capability to cross the BBB and drugs
      that can be safely administered at high doses to obtain therapeutic
      concentrations in the CNS are the most commonly used in the treatment of PCNSL.
      Consolidation after chemotherapy represents the best role for radiotherapy. Since
      this tumor has an infiltrative nature, the whole brain should be irradiated, with
      increased risk of severe neurotoxicity. Some authorities are investigating in
      randomized trials the impact on outcome and neurotolerability of replacing
      consolidation radiotherapy with other strategies, like high dose chemotherapy
      supported by autologous stem cell transplantation. The rationale for the use of
      this strategy is the administration of high doses of cytostatics to achieve
      therapeutic concentrations in sanctuaries, CNS organs and lymphoma tissues and to
      overcome drug resistance mechanisms. Future therapeutic progresses in PCNSL will
      be based on the expansion of molecular and biological knowledge, the improvement
      of therapeutic efficacy and the prevention of iatrogenic neurotoxicity.

PMID- 22409829
TI  - Vitamin C and asthma in children: modification of the effect by age, exposure to
      dampness and the severity of asthma.
AB  - BACKGROUND: We previously found a significant benefit of vitamin C
      supplementation in asthmatic children. PURPOSE: To test whether the effect of
      vitamin C on asthma is heterogeneous over the participant population. METHODS:
      Egyptian asthmatic children between 7 and 10 years of age (n = 60) were included
      in the cross-over trial. They were administered 0.2 grams per day of vitamin C
      and placebo for separate 6-week periods. The variation in the vitamin C effect on
      two clinically relevant outcomes was analyzed: the childhood asthma control test
      (C-ACT), which measures the severity of asthma symptoms (the scale ranges from 0
      to 27 points, < 20 points indicating unsatisfactory asthma control), and FEV1. We
      used linear modeling to examine the variation of the vitamin C effect in the
      subgroups. RESULTS: The effect of vitamin C on the C-ACT was significantly
      modified by age and baseline C-ACT levels. In the children aged 7.0-8.2 years
      with a baseline C-ACT of 18 to 19 points, vitamin C increased the C-ACT score by
      4.2 points (95% CI: 3.3-5.3); whereas in the children aged 8.3-10 years who had a
      baseline C-ACT of 14 to 15 points, vitamin C increased the C-ACT score by only
      1.3 points (95% CI: 0.1-2.5). The effect of vitamin C on the FEV1 levels was
      significantly modified by age and exposure to dampness. In the children aged 7.0
      8.2 years with no exposure to dampness, vitamin C increased the FEV1 level by 37%
      (95% CI: 34-40%), whereas in the children aged 8.3-10 years with exposure to
      dampness or mold in their bedroom more than one year prior to the study, vitamin
      C increased the FEV1 level by only 21% (95% CI: 18-25%). CONCLUSIONS: We found
      strong evidence that the effect of vitamin C on asthmatic children is
      heterogeneous. Further research is needed to confirm our findings and identify
      the groups of children who would receive the greatest benefit from vitamin C
      supplementation.

PMID- 22409830
TI  - Comment: low dental caries rate in Neandertals: the result of diet or the oral
      flora composition?
AB  - Dental caries is an infectious disease caused by oral acidophilic bacteria
      feeding on fermentable sugars, e.g. Streptococcus mutans. The frequency of dental
      caries in Neandertals was very low. This was usually explained as the result of a
      low-sugar diet. Recent research, however, revealed some regional differences
      between European and Near Eastern Neandertals, with the latter consuming
      considerable amounts of plants including highly cariogenic dates. This discovery,
      compared with the results of research on genetic diversity of S. mutans, may
      suggest that this species, and perhaps other most virulent species, were absent
      in the oral flora of Neandertals.

PMID- 22409831
TI  - Nonhuman primate models of thrombosis.
AB  - Arterial thrombosis and its associated clinical diseases make it one of the
      leading causes of death today. The majority of myocardial infarctions are caused
      by arterial thrombosis with acute myocardial infarction being the number one
      killer of individuals at a premature age. Venous thromboembolism (VTE) has a
      national morbidity exceeding 900,000 persons, with approximately 300,000
      fatalities annually. Unfortunately, the incidence of this disease has not
      significantly changed over the past 25 years, possibly due to the increasing
      identification of new cases. The use of nonhuman primate models of vascular
      disease is essential to our understanding of the mechanisms that promote
      thrombogenesis in humans. These large animal models have close phylogenetic,
      anatomic, and physiologic similarities to humans, which make them necessary for
      many translational vascular research applications. Thus, translational animal
      models can help accelerate the development of new pharmacologic and medical
      devices targeted at limiting vascular inflammation and thrombosis. This review
      provides a brief overview of several nonhuman primate models used for the
      development of novel interventions directed at thrombotic diseases.

PMID- 22409832
TI  - Evaluating a team-based approach to research capacity building using a matched
      pairs study design.
AB  - BACKGROUND: There is a continuing need for research capacity building initiatives
      for primary health care professionals. Historically strategies have focused on
      interventions aimed at individuals but more recently theoretical frameworks have
      proposed team-based approaches. Few studies have evaluated these new approaches.
      This study aims to evaluate a team-based approach to research capacity building
      (RCB) in primary health using a validated quantitative measure of research
      capacity in individual, team and organisation domains. METHODS: A non-randomised
      matched-pairs trial design was used to evaluate the impact of a multi-strategy
      research capacity building intervention. Four intervention teams recruited from
      one health service district were compared with four control teams from outside
      the district, matched on service role and approximate size. All were multi
      disciplinary allied health teams with a primary health care role. Random-effects
      mixed models, adjusting for the potential clustering effect of teams, were used
      to determine the significance of changes in mean scores from pre- to post
      intervention. Comparisons of intervention versus control groups were made for
      each of the three domains: individual, team and organisation. The Individual
      Domain measures the research skills of the individual, whereas Team and
      Organisation Domains measure the team/organisation's capacity to support and
      foster research, including research culture. RESULTS: In all three domains
      (individual, team and organisation) there were no occasions where improvements
      were significantly greater for the control group (comprising the four control
      teams, n = 32) compared to the intervention group (comprising the four
      intervention teams, n = 37) either in total domain score or domain item scores.
      However, the intervention group had a significantly greater improvement in
      adjusted scores for the Individual Domain total score and for six of the fifteen
      Individual Domain items, and to a lesser extent with Team and Organisation
      Domains (two items in the Team and one in the Organisation domains). CONCLUSIONS:
      A team-based approach to RCB resulted in considerable improvements in research
      skills held by individuals for the intervention group compared to controls; and
      some improvements in the team and organisation's capacity to support research.
      More strategies targeted at team and organisation research-related policies and
      procedures may have resulted in increased improvements in these domains.

PMID- 22409833
TI  - Prenatal predictors for father-infant attachment after childbirth.
AB  - AIMS AND OBJECTIVES: This study aims to assess expectant fathers' social support,
      marital intimacy and health status during the third trimester of their partners'
      pregnancies. Further, we investigate the predictors of father-infant attachment
      after childbirth. BACKGROUND: Becoming a father is a transition. Research has
      focused more on mothers than on fathers, even though the philosophy of the
      maternal care system is about providing family-centred care. The psychological
      status of first-time fathers and the attachment they have to their infants have
      received little attention in the research. DESIGN: A repeated measures study
      design. METHODS: A total of 195 first-time fathers were recruited during the
      third trimester of their partners' pregnancies. During that time, they completed
      the Social Support Scale, the Marital Intimacy Scale and the Chinese Health
      Questionnaire. After childbirth, they completed the Paternal Attachment Inventory
      during the one-week postpartum period. RESULTS: The fathers who perceived more
      marital intimacy and support from their partners were more attached to their
      infants. Moreover, marital intimacy and partner support were important predictors
      for father-infant attachment. CONCLUSIONS: Future research is warranted to
      determine the prenatal predictors of father-infant attachment for high-risk
      families. RELEVANCE TO CLINICAL PRACTICE: The philosophy of maternal care is
      family oriented; for health professionals, pregnancy is an important time to
      provide information and counsel couples. Interventions should not only target the
      health and well-being of expectant mothers but should also actively invite
      fathers to participate in prenatal care with their partners to facilitate marital
      intimacy and father-infant attachment.

PMID- 22409834
TI  - Buccoadhesive films for once-a-day administration of rivastigmine: systematic
      formulation development and pharmacokinetic evaluation.
AB  - CONTEXT: Rivastigmine, an anti-Alzheimer's drug, suffers from major predicaments
      like low oral bioavailability, severe GI adverse effects related to rapid
      fluctuations in drug plasma levels, and high frequency of dosing. OBJECTIVE: The
      present investigation aims at developing buccoadhesive films capable of
      delivering the drug in vivo in a sustained manner. Augmentation of drug
      bioavailability by the avoidance of first-pass effect through the buccal route
      and reduction in GI side effects would be other key advantages of this system.
      METHODS: Buccoadhesive films of rivastigmine were systematically designed and
      evaluated for in vitro drug release, ex vivo buccal permeation and ex vivo
      buccoadhesive strength. Optimal composition of the polymer blends was rationally
      chosen using a central composite design and overlay plot. In vivo pharmacokinetic
      studies were carried out in rabbits, and attempts were made to establish in
      vitro/ in vivo correlations (IVIVC). RESULTS: Besides possessing the requisite
      drug release regulation, the optimized formulation exhibited excellent
      buccoadhesion, and buccal permeation. Pharmacokinetic studies indicated extension
      of plasma drug levels and level A of IVIVC was successfully established.
      DISCUSSION: Excellent buccal bioadhesion and transmucosal permeation, coupled
      with drug release control, ratify the potential of the optimized formulation to
      deliver the drug in a controlled and site-specific manner. Successful
      establishment of IVIVC substantiated the judicious choice of in vitro dissolution
      media for simulating the in vivo conditions. CONCLUSION: Besides unraveling the
      polymer synergism, the study helped in developing an optimal once-a-day
      buccoadhesive drug delivery system exhibiting excellent trans-buccal permeation
      and buccoadhesive characteristics with improved bioavailability potential.

PMID- 22409836
TI  - Zwitterionic polymer-based platform with two-layer architecture for ultra low
      fouling and high protein loading.
AB  - High resistance to nonspecific adsorption typically accompanies loss of binding
      capacity and vice versa for many surface coatings and applications. In this
      study, a zwitterionic polycarboxybetaine acrylamide (pCB)-based binding platform
      with a "two-layer" structure for ultra low fouling and high protein loading
      properties was developed. The first pCB layer with a high packing density
      prepared under a water-free condition serves as a protective layer to resist
      nonspecific adsorption from complex media. The second pCB layer with a low
      packing density is used to achieve high protein binding capacity. Amounts of
      tetraethylthiuram disulfide (TED) and water in the reaction were varied to
      regulate the packing density and chain length of polymers, respectively, for the
      second pCB layer. The in situ modification of pCB films with antihuman thyroid
      stimulating hormone (TSH) IgG molecules and the detection of TSH antigens were
      employed to demonstrate high protein immobilization and high antigen detection
      capabilities of this "two-layer" structure. Undiluted blood plasma was used to
      test the nonfouling properties of this platform. Nonspecific and specific
      interactions were monitored by a surface plasmon resonance sensor. This work
      demonstrates great promise of this "two-layer" binding platform for the improved
      performance of biosensors.

PMID- 22409835
TI  - Gene expression profiling of peripheral blood mononuclear cells in the setting of
      peripheral arterial disease.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is a relatively common
      manifestation of systemic atherosclerosis that leads to progressive narrowing of
      the lumen of leg arteries. Circulating monocytes are in contact with the arterial
      wall and can serve as reporters of vascular pathology in the setting of PAD. We
      performed gene expression analysis of peripheral blood mononuclear cells (PBMC)
      in patients with PAD and controls without PAD to identify differentially
      regulated genes. METHODS: PAD was defined as an ankle brachial index (ABI) <=0.9
      (n = 19) while age and gender matched controls had an ABI > 1.0 (n = 18).
      Microarray analysis was performed using Affymetrix HG-U133 plus 2.0 gene chips
      and analyzed using GeneSpring GX 11.0. Gene expression data was normalized using
      Robust Multichip Analysis (RMA) normalization method, differential expression was
      defined as a fold change >=1.5, followed by unpaired Mann-Whitney test (P < 0.05)
      and correction for multiple testing by Benjamini and Hochberg False Discovery
      Rate. Meta-analysis of differentially expressed genes was performed using an
      integrated bioinformatics pipeline with tools for enrichment analysis using Gene
      Ontology (GO) terms, pathway analysis using Kyoto Encyclopedia of Genes and
      Genomes (KEGG), molecular event enrichment using Reactome annotations and network
      analysis using Ingenuity Pathway Analysis suite. Extensive biocuration was also
      performed to understand the functional context of genes. RESULTS: We identified
      87 genes differentially expressed in the setting of PAD; 40 genes were
      upregulated and 47 genes were downregulated. We employed an integrated
      bioinformatics pipeline coupled with literature curation to characterize the
      functional coherence of differentially regulated genes. CONCLUSION: Notably,
      upregulated genes mediate immune response, inflammation, apoptosis, stress
      response, phosphorylation, hemostasis, platelet activation and platelet
      aggregation. Downregulated genes included several genes from the zinc finger
      family that are involved in transcriptional regulation. These results provide
      insights into molecular mechanisms relevant to the pathophysiology of PAD.

PMID- 22409838
TI  - [Smoking intervention in patients with cardiovascular diseases].
AB  - Smoking tobacco is the main cardiovascular risk factor and has a dose-dependent
      response. It has been shown that an aggressive policy, not only against
      consumption, achieves a significant decrease in cardiovascular deaths. Thus, we
      must provide and carry out activities to prevent or decrease the incidence of
      smoking (primary prevention), and to the early detection of the smoker and to
      reduce the prevalence (secondary prevention), and lastly to act on the effects of
      tobacco smoke, preventing complication and remissions (tertiary prevention).
      Thus, all health care levels must act in order that smokers do not develop
      cardiovascular disease when they quit smoking, both from Primary, as well as
      specialist care.

PMID- 22409837
TI  - Evaluation of drug administration errors in a teaching hospital.
AB  - BACKGROUND: Medication errors can occur at any of the three steps of the
      medication use process: prescribing, dispensing and administration. We aimed to
      determine the incidence, type and clinical importance of drug administration
      errors and to identify risk factors. METHODS: Prospective study based on
      disguised observation technique in four wards in a teaching hospital in Paris,
      France (800 beds). A pharmacist accompanied nurses and witnessed the preparation
      and administration of drugs to all patients during the three drug rounds on each
      of six days per ward. Main outcomes were number, type and clinical importance of
      errors and associated risk factors. Drug administration error rate was calculated
      with and without wrong time errors. Relationship between the occurrence of errors
      and potential risk factors were investigated using logistic regression models
      with random effects. RESULTS: Twenty-eight nurses caring for 108 patients were
      observed. Among 1501 opportunities for error, 415 administrations (430 errors)
      with one or more errors were detected (27.6%). There were 312 wrong time errors,
      ten simultaneously with another type of error, resulting in an error rate without
      wrong time error of 7.5% (113/1501). The most frequently administered drugs were
      the cardiovascular drugs (425/1501, 28.3%). The highest risks of error in a drug
      administration were for dermatological drugs. No potentially life-threatening
      errors were witnessed and 6% of errors were classified as having a serious or
      significant impact on patients (mainly omission). In multivariate analysis, the
      occurrence of errors was associated with drug administration route, drug
      classification (ATC) and the number of patient under the nurse's care.
      CONCLUSION: Medication administration errors are frequent. The identification of
      its determinants helps to undertake designed interventions.

PMID- 22409839
TI  - Vaccination reduces macrophage infiltration in bronchus-associated lymphoid
      tissue in pigs infected with a highly virulent Mycoplasma hyopneumoniae strain.
AB  - BACKGROUND: Mycoplasma hyopneumoniae is the causative agent of enzootic pneumonia
      and is responsible for significant economic losses to the pig industry. To better
      understand the mode of action of a commercial, adjuvanted, inactivated whole cell
      vaccine and the influence of diversity on the efficacy of vaccination, we
      investigated samples from vaccinated and non-vaccinated pigs experimentally
      infected with either a low (LV) or a highly virulent (HV) M. hyopneumoniae
      strain. Non-vaccinated and sham-infected control groups were included. Lung
      tissue samples collected at 4 and 8 weeks post infection (PI) were
      immunohistochemically tested for the presence of T-lymphocytes, B-lymphocytes and
      macrophages in the bronchus-associated lymphoid tissue (BALT). The number of M.
      hyopneumoniae organisms in bronchoalveolar lavage (BAL) fluid was determined
      using quantitative PCR at 4 and 8 weeks PI. Serum antibodies against M.
      hyopneumoniae were determined at 0, 2, 4, 6 and 8 weeks PI. RESULTS: The
      immunostaining revealed a lower density of macrophages in the BALT of the
      vaccinated groups compared to the non-vaccinated groups. The highest number of M.
      hyopneumoniae organisms in the BAL fluid was measured at 4 weeks PI for the HV
      strain and at 8 weeks PI for the LV strain. Vaccination reduced the number of
      organisms non-significantly, though for the HV strain the reduction was
      clinically more relevant than for the LV strain. At the level of the individual
      pigs, a higher lung lesion score was associated with more M. hyopneumoniae
      organisms in the lungs and a higher density of the investigated immune cells in
      the BALT. CONCLUSIONS: In conclusion, the infiltration of macrophages after
      infection with M. hyopneumoniae is reduced by vaccination. The M. hyopneumoniae
      replication in the lungs is also reduced in vaccinated pigs, though the HV strain
      is inhibited more than the LV strain.

PMID- 22409840
TI  - [The effect of cryoglobulinemia on the antiviral therapy in patients with chronic
      hepatitis C].
AB  - OBJECTIVE: To investigate the possible influence of cryoglobulinemia on the
      antiviral effect in chronic hepatitis C patients, who were treated with
      combination therapy of pegylated interferon alpha-2a and ribavirin. METHODS:
      Forty consecutive patients with chronic hepatitis C (CHC) were enrolled in the
      study. They received pegylated interferon alfa-2a (40kD, 180mug/w) along with
      ribavirin. Baseline cryoglobulins were detected in the sera by cryoprecipitation.
      Hepatitis C virus (HCV) genotyping was performed and HCV viral load was detected
      at baseline, and at 4, 12 weeks during treatment, 24 weeks after cessation of
      treatment. RESULTS: Eighteen (45.0%) patients infected with HCV were
      cryoglobulins positive at baseline. Mean serum HCV RNA level in cryoglobulins
      positive patients was higher than that in cryoglobulins negative patients (6.36+/
      0.63 vs. 5.70+/-1.20, P = 0.032). The rapid virological response (RVR) rate was
      statically different between cryoglobulins positive patients and cryoglobulins
      negative ones (6/18, 33.3% vs. 15/22, 68.2%, P = 0.028). In contrast, no
      difference was found in early virological response (EVR) rate between the
      cryoglobulins positive patients and cryoglobulins negative ones (14/17, 82.4% vs.
      18/21, 85.7%, P = 1.0). Sustained virological response (SVR) rate in
      cryoglobulins positive and cryoglobulins negative was different (0/3, 0 vs 6/6,
      100%, P = 0.012). The rate of patients achieved RVR was different between the
      patients infected with HCV genotype 1 b of two groups (cryoglobulins positive:
      2/13, 15.4% vs cryoglobulins negative 14/21; 66.7%, P = 0.005). However, the rate
      of EVR in patients infected HCV genotype 1 b was not statistically different
      (cryoglobulins positive: 9/12, 75.0% vs. cryoglobulins negative 17/20; 81.2%, P =
      0.647). CONCLUSION: The rates of RVR and SVR achievement in cryoglobulinemia
      positive CHC patients are lower than those in cryoglobulinemia negative CHC
      patients.

PMID- 22409841
TI  - [Detection of core antigen of hepatitis virus C in patients infected with
      hepatitis virus C and B].
AB  - OBJECTIVE: To observe the effect of hepatitis virus B on the detection rate of
      core antigen of hepatitis virus C in sera of chronic hepatitis C patients.
      METHOD: HCVcAg and HCV RNA in sera were detected in 88 patients with chronic
      hepatitis C and 62 patients co-infected with HCV and HBV. At the same time, HBV
      DNA and HBeAg in sera were detected in 62 patients infected with HCV and HBV.
      Then we analyzed the correlation between HCVcAg and HBeAg/HBV DNA. The detection
      rates of HCVcAg in 88 patients with chronic hepatitis C and 62 patients co
      infected with HCV and HBV were 72.7% (64/88) and 38.7% (24/62), respectively (x2
      = 17.358, P less than 0.01). RESULTS: The detection rates of HCV RNA in 88
      patients with chronic hepatitis C and 62 patients co-infected with HCV and HBV
      was 81.8% (72/88) and 53.2% (33/62)respectively (x2=20.110, P less than 0.01). In
      62 patients infected with HCV and HBV, the detection rate of HCVcAg in HBeAg
      positive patients and HBeAg negative patients were 28.6% (12/42) and 60% (12/20),
      respectively (x2 = 7.547, P = 0.011). Moreover, the positive rates of HBV DNA in
      HBeAg positive patients and HBeAg negative patients were 42.9% (18/42) and 80%
      (16/20), respectively (P more than 0.05). The detection rates of HCVcAg in HBV
      DNA positive patients and HBV DNA negative patients were 39.1% (18/46) and 37.5%
      (6/16), respectively (x2 = 0.013, P = 0.908). Compared with the detection rates
      of HCVcAg in patients only infected with HCV, the detection rate of HCVcAg in
      HBeAg or HBV DNA negative patients infected with HCV and HBV were 60% (12/20) (x2
      = 1.266, P = 0.261) and 37.5% (6/16) (x2 =7.635, P less than 0.01), respectively.
      CONCLUSION: The detection rate of HCVcAg in patients infected with HCV and HBV is
      relatively low. The reason is possibly that HBeAg inhibits duplication of HCV and
      decreases the expression of HCVcAg.

PMID- 22409842
TI  - [Analysis of hepatitis C virus (HCV) subtypes in HIV/HCV co-infected and HCV mono
      infected individuals in Guangdong province].
AB  - OBJECTIVE: To explore the transmission routes, genotypes/subtypes distribution
      and genetic character of HCV in HIV/HCV co-infected and HCV mono-infected
      individuals in Guangdong Province. METHODS: Reverse transcription (RT) nested PCR
      was performed to amplify the HCV NS5B gene region from 95 HIV/HCV co-infected and
      99 HCV mono-infected individuals lived in Guangdong province. The PCR products
      were then sequenced for HCV subtyping. Genetic analysis was done by MEGA4
      software. RESULTS: (1) HIV/HCV co-infected individuals infected HCV mostly
      through injection drug use (IDU, 78.9%), the HCV subtypes were identified as 6a
      (53.7%), 3a (17.9%), 1b (15.8%), 3b (11.6%) and 1a (1.0%) respectively, the
      genetic distance within subtype 1b was longer than those within other subtypes,
      the predominant HCV subtype in HIV/HCV co-infected individuals infected through
      IDU was 6a (60.0%). (2) HCV mono-infected individuals infected HCV mostly through
      blood or blood products transfusions (80.8%), the HCV subtypes were identified as
      1b (67.7%), 6a (17.2%), 3a (6.1%), 2a (5.0%), 3b (2.0%), 4a (1.0%) and 5a (1.0%)
      respectively, the genetic distance within subtype 1b was also longer than those
      within other subtypes, the predominant HCV subtype in HCV mono-infected
      individuals infected through blood or blood products transfusions was 1b (76.2%).
      CONCLUSION: The diversity of HCV subtypes in HIV/HCV co-infected and HCV mono
      infected individuals in Guangdong Province was high, both the major transmission
      route and HCV subtype between HIV/HCV co-infected individuals and HCV mono
      infected individuals were different.

PMID- 22409843
TI  - [The impact of early rapid virological response on the outcomes of hepatitis B
      associated acute on chronic liver failure during antiviral treatment].
AB  - OBJECTIVE: To investigate the impact of early rapid virological response on the
      outcomes of hepatitis B associated acute on chronic liver failure during
      antiviral treatment. METHODS: 106 acute on chronic liver failure patients in our
      hospital from January 2008 to July 2010 were enrolled in present study
      retrospectively. Besides internal medicine therapy, all patients received
      lamivudine (100 mg/d) or entecavir (0.5 mg/d) treatment. The profile of liver
      biochemistry, prothrombin time activity and viral load were detected at baseline
      and week 4, respectively. The patients were divided into HBV DNA negative group
      and HBV DNA positive group according to the viral load at week 4. The clinical
      features and treatment outcomes were compared between groups. Frequency variables
      were compared by x2 test or Fisher's exact test. Continuous variables were
      compared using independent samples T-test. The factors that impact on the
      treatment outcomes were determined using stepwise multivariate logistic
      regression analysis. RESULTS: At the week 4, the TBil and PTA in HBV DNA positive
      group [(261.6+/-205.6)mumol/L and 44.7%+/-19.7%, respectively] were significantly
      different from those in HBV DNA negative group [(160.1+/-173.4) mumol/L and
      56.8%+/-23.1%, respectively] ( t = 2.190 and -2.077, respectively, P less than
      0.05). The non-effective rate of HBVDNA positive group (50%, 9/18) was
      significantly higher than that of HBV DNA negative group (14.8%, 13/88) (x2 =
      9.235, P less than 0.01). By using stepwise multivariate logistic regression
      analysis, the disease stage and HBV DNA undetectable at week 4 were the
      independent factor. The OR values of disease stage and HBV DNA undetectable were
      6.559 and 0.209, respectively, and 95% CI was 2.316~18.576 and 0.058~0.747,
      respectively. CONCLUSION: The rapid suppression of viral load by nucleotide
      analogue may improve the efficacy of hepatitis B associated acute on chronic
      liver failure treatment. The early rapid virological response within first 4
      weeks may contribute to the prediction of the treatment outcomes.

PMID- 22409844
TI  - [Predictors and scoring system for sustained complete response to conventional
      interferon-alpha therapy on chronic hepatitis B].
AB  - OBJECTIVE: To establish a predictive scoring system which may serve for the
      prediction of sustained response to conventional interferon-alpha (IFN-alpha)
      treatment on chronic hepatitis B. METHODS: A total of 474 IFN-alpha treated
      hepatitis B virus e antigen (HBeAg)-positive patients were enrolled in the
      present study. The patients' baseline characteristics, such as age, gender,
      aminotransferases, activity grading (G) of intrahepatic inflammation, score (S)
      of liver fibrosis, hepatitis B virus (HBV) DNA and genotype were evaluated;
      therapy duration and response of each patient at the 24th wk after cessation of
      IFN-alpha treatment were also recorded. A predictive scoring system for a
      sustained complete response (CR) to IFN-alpha therapy was established based on
      genetic algorithm. About 10% of the patients were randomly drawn out as the test
      set. Responses to IFN-alpha therapy were divided into CR, partial response (PR)
      and non-response (NR). The mixed set of PR and NR was recorded as PR + NR.
      RESULTS: For the scoring system, the sensitivity and specificity were 78.8% and
      80.6%, respectively. CONCLUSION: This SCR scoring system has satisfying
      prediction efficiency and is easily employed in clinical practice. With this
      scoring system, practitioners can propose individualized decisions that have an
      integrated foundation on both evidence-based medicine and personal
      characteristics.

PMID- 22409845
TI  - [The discrepancy of HBsAg titre and HBV DNA in patients with chronic hepatitis B,
      HBV-related liver cirrhosis and hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the discrepancy of HBsAg titre and correlation of HBV
      DNA levels among patients with chronic hepatitis B (CHB), HBV-related liver
      cirrhosis (LC) and hepatocellular carcinoma (HCC). METHODS: HBsAg titre and HBV
      DNA in serum samples were measured among 47 CHB, 72 LC and 54 HCC cases using
      Abbott chemiluminescence and fluorescence quantitative PCR, respectively.
      Statistical analyses among multiple groups, between two groups and about the
      correlation were performed using Kruskal-Wallis test, Mann-Whitney U test and
      Spearman test, respectively. RESULTS: The median HBsAg titre level in serum
      samples decreased from 2361.10 IU/ml in CHB cohort to 1001.64 IU/ml in LC cohort
      and 594.35 IU/ml in HCC cohort, suggesting a statistically significant difference
      (x2 = 24.394, P less than 0.05). Moreover, HBsAg titre in CHB group was
      significantly higher than that in LC group ( Z = -3.754, P less than 0.05). CHB
      patients had significantly higher HBsAg titre than HCC cases ( Z = -4.630, P less
      than 0.05). However, there was no statistically significant difference in HBsAg
      titre between LC and HCC group. Among HBeAg positive patients, HBsAg titre
      decreased from 3259.83 IU/ml in CHB group to 1077.30 IU/ml in LC group and 789.72
      IU/ml in HCC group, indicating a significant difference (x2 = 15.643, P less than
      0.01). Among HBeAg negative patients, HBsAg titre declined from 1669.00 IU/ml in
      CHB group to 1001.64 IU/ml in LC group and 582.05 IU/ml in HCC group, suggesting
      of a significant difference (x2 = 6.423, P less than 0.05). Positive correlation
      between HBsAg titre and HBV DNA was found in CHB ( r = 0.297, P less than 0.05),
      LC (r = 0.346, P less than 0.05) and HCC (r = 0.452, P less than 0.05),
      respectively. CONCLUSION: HBsAg titre level in serum decreased progressively from
      CHB to LC and HCC group. There were positive correlations between HBsAg titre and
      HBV DNA level in CHB, LC and HCC.

PMID- 22409846
TI  - [Study of the effect and mechanism of spastic paraplegia 21 protein on the
      replication of hepatitis B virus].
AB  - OBJECTIVE: To study the effect of human spastic paraplegia 21 protein (SPG21) on
      the replication of hepatitis B virus(HBV) and its regulatory mechanism. METHODS:
      HBV infectious clone pHBV1.3 and its promoter pHBV-Luc were transfected
      respectively into HepG2 cells with SPG21 of different concentrations, HBsAg and
      HBeAg in the supernatants were measured by enzyme linked immunosorbent assay
      (ELISA), expression of HBV core mRNA and protein were detected by RT-PCR and
      western blot, covalently closed circular DNA(ccc DNA) levels were measured by
      real-time PCR, and HBV promoter activity was measured by luminometer fluorescence
      detector. RESULTS: Expression of HBsAg, HBeAg, HBV core protein and cccDNA were
      upregulated by SPG21 as well as HBV promoter activity in a dose-dependent
      approach. The activity of HBV promoter increased to 1.63, 3.09 and 4.66 times in
      HepG2 cells treated with 50mug/ml, 100mug/ml and 200mug/ml SPG21 respectively
      during 48 hour-treated ( P less than 0.05), as compared to the control group.
      CONCLUSIONS: SPG21 can enhance the replication of HBV in HepG2 cells.

PMID- 22409847
TI  - [Effects of HCV core protein on the expression of hypoxia-inducible factor 1
      alpha and vascular endothelial growth factor].
AB  - OBJECTIVE: To investigate the effect of core protein of hepatitis C virus (HCV)
      on the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular
      endothelial growth factor (VEGF). METHODS: Huh7.5.1 cells were transfected with
      plasmid flag2B-core carrying HCV core gene, expression of HIF-1alpha and VEGF
      were measured by reverse transcription-polymorphism chain reaction (RT-PCR) and
      western blot. Enzyme link immunoabsorbent assay (ELISA) were used to detect the
      level of VEGF in the supernatants. RESULTS: The expression of HIF-1alpha and VEGF
      mRNA and protein were upregulated after flag2B-core was transfected into Huh7.5.1
      cells, and VEGF level in the supernatant was significant elevated as compared to
      controls [(654.5+/-43.7) pg/ml vs (365.9+/-26.8) pg/ml, t = 653.1%, P less than
      0.01]. The expression of HIF-1alpha and VEGF mRNA and protein were downregulated
      after flag2B-core and HIF-1alpha siRNA were co-transfected into Huh7.5.1 cells,
      and VEGF level in the supernatant was significantly reduced as compared to
      controls [(389.2+/-29.6) pg/ml vs (768.8+/-47.3)pg/ml, t = 1330.22, P less than
      0.01]. CONCLUSIONS: HCV core protein enhances the expression of HIF-1alpha and
      VEGF. HCV may regulate the expression of HIF-1alpha and VEGF via the core
      protein.

PMID- 22409848
TI  - [Expressions and significance of COX-2 and P-gp in human hepatocellular carcinoma
      tissues].
AB  - OBJECTIVE: To investigate the effect of the COX-2 gene on the oncogenesis and
      development of the hepatocellular carcinoma and the influence of COX-2 gene on
      the expression of P-gp protein. METHOD: Fifty-two pieces of the hepatocellular
      carcinoma samples and 20 cases of normal liver samples were collected from the
      patients operated from October 2003 to June 2005. RT-PCR and immunohistochemistry
      staining were employed to detect the COX-2 mRNA as well as P-gp protein in the
      normal liver tissues and the carcinoma tissues. Meanwhile, the expression of the
      mdr 1 mRNA in the carcinoma tissues was also determined and the correlation
      between the expressions of the COX-2 and P-gp was investigated. RESULTS: No
      expression of the COX-2 in the normal liver tissue was detected. The positive
      expression of COX-2 in the low and middle differentiated carcinoma was elevated
      significantly as compared with that in the high differentiated carcinoma tissue
      (x2 = 6.80, P less than 0.01). The positive expression of the COX-2 in the HBSAg
      (+) carcinoma tissue was significantly higher as compared with that in the HBSAg
      (-) carcinoma (x2 = 4.70, P less than 0.05), and the carcinoma in combination
      with cirrhosis also showed significantly higher in expression of COX-2 than the
      carcinoma without cirrhosis (x2 = 7.51, P less than 0.01). The mdr1 mRNA was
      found both expressed in the normal and carcinoma tissues. The expression of COX-2
      mRNA was found in the carcinoma, but not found in the normal tissues. The COX-2
      mRNA and mdr1 mRNA was found both expressed in the normal and carcinoma tissues.
      The correlation coefficient between COX-2 and mdr1 mRNA was 0.563 ( P less than
      0.01). CONCLUSION: The results indicated that Cox-2 gene might involved in the
      multidrug resistance of the hepatocellular carcinoma mediated by P-gp.

PMID- 22409849
TI  - [Clinical efficacy and prognostic factors for cryoablation patients with advanced
      hepatocellular carcinoma].
AB  - OBJECTIVES: Investigate the clinical efficacy of cryotherapy ablation treatment
      for advanced hepatocellular carcinoma. analyse the predictive factors of
      cryotherapy ablation treatment. METHODS: There were 190 cases of hepatitis B
      related HCC patients with advanced HCC from 2005 to 2008 in our hospital. By
      using clinical cohort method, they included cryoablation group (147 cases) and
      control group (43 cases), The median survival time and time to disease
      progression were compared. Evaluate clinical significance of age, gender,
      location of portal vein tumor thrombus, HBeAg, tumor histological grade, Child
      Pugh classification, end-stage liver disease (MELD) score, advanced liver cancer
      prediction system (ALCPS) score and the Eastern Cooperative Oncology Group
      performance status (ECOG PS) score for predicting the efficacy of cryoablation.
      Group rates were compared with the x2 test, survival analysis by using Kaplan
      Meier method, survival rates were compared by Log-rank analysis; multiple factor
      survival analysis by using Cox regression model. RESULTS: Median survival time of
      cryoablation group and Control group was 7.5 (4.2 to 14.6) months and 3.2 (1.2 to
      8.6) months, median TTP was 3.5 (2.5 to 4.5) months and 1.5 (1.0 to 3.5 months),
      the differences were statistically significant ( P less than 0.05 ). Median OS
      and TTP of advanced HCC patients who had Well-differentiated tumor, Child-pugh A
      class and low score of MELD score, ALCPS score, ECOG PS score were significantly
      longer than the poorly differentiate, Child-Pugh B-class and the high those
      scores ( P less than 0.05). ECOG PS ( P less than 0.05, 95% CI 1.074 to 2.143)
      and ALCPS (P less than 0.05, 95% CI 1.005 to 2.121) were independent predictors
      for OS of advanced HCC. CONCLUSION: Cryoablation treatment can prolong median OS
      and TTP of advanced HCC; ECOG PS and ALCPS are important predictors for survival
      time of advanced HCC.

PMID- 22409850
TI  - [Effect of Saikosaponins-d on reversing malignant phenotype of HepG2 cells in
      vitro].
AB  - OBJECTIVE: To observe the effect of SSd on reversing the malignant phenotype of
      HepG2 cells and to investigate its mechanism in order to prove that SSd is a new
      choice to prevent and treat HCC. METHODS: HepG2 cells were cultured and treated
      by different concentration (0 mg/L, 2.5 mg/L, 5.0 mg/L, 10.0 mg/L and 20.0 mg/L)
      of SSd for 24 h, and treated by 10 mg/L of SSd for 0 h, 6 h, 12 h, 24 h, 48 h and
      72h respectively. The cell inhibition rates were measured by MTT assay. Then
      cells were treated by 10 mg/L SSd for 48 hr in experimental group and treated by
      no SSd as a control, their morphological changes were observed by contrast phase
      microscope. The concentrations of ALB and AFP in clear supernatant liquid of
      cells were detected by radio-immunity and chemiluminescence. The cell migration
      rates were observed by transwell method, the relative expression levels of p27
      mRNA were measured by RT-PCR. RESULTS: The inhibitive effect of 10 mg/L SSd was
      the most significant among different concentrations ( F = 265.06, P less than
      0.01). The shape of HepG2 from experimental group turned into small and round,
      and their volume ratios of nucleus to plasma decreased. ALB in supernatant liquid
      of HepG2 was higher ( t = 7.83, P less than 0.05, and its AFP was lower ( t = 
      10.72, P less than 0.01) as compared to control group. Cells migrated were fewer
      and p27 mRNA expression of HepG2 was higher in experimental group than that in
      control group (t = 22.00, P less than 0.05). CONCLUSION: SSd could reverse the
      malignant phenotype of HepG2 cells. It was suggested that the up-regulation of
      p27 mRNA expression play an important role in the differentiation of HepG2 cells
      treated by SSd.

PMID- 22409851
TI  - [Effect of hepatitis B virus X protein on expression of lipid metabolism-related
      genes in HepG2 cells].
AB  - OBJECTIVE: To investigate the effect of Hepatitis B Virus X Protein (HBx) on the
      expression of lipid metabolism-related genes and its role in pathogenesis of
      hepatocyte fatty degeneration. METHODS: Hepatitis B Virus X gene eukaryon
      expression vector pIRES2-eGFP-HBx was transfected into HepG2 cells to establish
      HepG2/HBx cell model for HBx expression. HepG2 cells transfected with pIRES2-eGFP
      (HepG2/pIRES2 cell) and non-transfected were used as controls. At 24, 48 and 72
      hours after transfection, the expression of green fluorescent protein (GFP) was
      observed by fluorescence microscope and the triglyceride(TG) content was
      detected. RT-PCR and Western blot were applied to detect the levels of sterol
      regulatory element binding protein-1 (SREBP-1), liver x receptor alpha (LXRalpha)
      mRNA and the levels of HBx, LXRalpha and fatty acid synthase (FAS) protein. At
      24, 48 and 72 hours after transfection, the expression of GFP was found in
      HepG2/HBx and HepG2/pIRES2 cells, and increased gradually. The expression of HBx
      was detected only in HepG2/HBx cells, and was increased with time after
      transfection (F = 32.21, P less than 0.01). These suggested successful obtaining
      of HepG2-HBx cell model for HBx expression. RESULTS: At 24h, 48h and 72h after
      transfection, the expression levels of LXRalpha mRNA (0.386+/-0.055, 0.505+/
      0.071, 0.649+/-0.058 ) and SREBP-1 mRNA (0.395+/-0.055, 0.548+/-0.047, 0.795+/
      0.058), as well as the levels of LXRalpha protein(0.178+/-0.036, 0.263+/-0.047,
      0.347+/-0.058) and FAS protein(0.436+/-0.055, 0.608+/-0.053, 0.827+/-0.046) in
      HepG2-HBx group were dramatically higher than those in the controls at the same
      time points (all P less than 0.05/0.01), and were gradually increased with time
      (all P less than 0.05/0.01). A positive correlationship was observed between HBX
      protein level and the LXRalpha, SREbP-1 mRNA and LXRalpha, FAS protein levels.
      The difference of TG content between HepG2/HBx group and control groups was not
      statistically significant (P more than 0.05). CONCLUSIONS: HBx-LXRalpha-SREBP
      1/FAS pathway suggested regulating transcription and expression of lipid
      metabolism-related genes, which might be one of the important molecular mechanism
      causing hepatocyte fatty degeneration.

PMID- 22409852
TI  - [Based on the low-density cDNA Macroarray for screening of antiviral proteins of
      IFNa tissues].
AB  - OBJECTIVE: To screen the gene expression profiles of IFN-alpha antiviral proteins
      based on a low-density cDNA Macroarray, and to explore the relationship between
      the expression of antiviral protein and the HBV replication. METHODS: The HepG2
      and HepG2.2.15 cells were treated with various concentrations of IFN-alpha (0
      IU/ml, 100 IU/ml, 1000 IU/ml) of IFN-alpha for 6 h, and then the low-density cDNA
      Macroarray was used for analysing the expression profiles of antiviral genes and
      screening differential expressions of antiviral proteins. Meanwhile, the HepG2
      cells were transiently transfected with HBV core protein-expressed plasmid pHBc
      EGFP, and the expressions of antiviral proteins were analysed by RT-PCR assay.
      Moreover, the HepG2.2.15 cells were also transfected with the antiviral protein
      expressed plasmid pcDNA3.1-Flag-MxA. ELISA was used for analysing the secreted
      HBV antigens, while dot blot and Southern blot were applied for analysing the
      extracellular HBV DNA and intracellular replicative intermediate HBV DNA in
      HepG2.2.15 cells. All data were presented as mean+/-SD and analyzed using the t
      test and one-way analysis of variance (ANOVA) in the experiments. RESULTS: The
      Macroarray results suggested that the expression of IFN-alpha antiviral genes
      like 6-16, IFITM1, IFITM2, IFITM3 and RING4 in HepG2.2.15 cells were partially
      inhibited. More importantly, it was found, in this research, the expression of
      antiviral protein MxA in HepG2.2.15 cells was completely suppressed. RT-PCR
      analysis indicated that the expression of MxA was also significantly decreased in
      HepG2 cells transfected with pHBc-EGFP plasmid. Although HepG2.2.15 cells
      transfected with pcDNA3.1-Flag-MxA plasmid could not inhibit extracellular HBV
      DNA and intracellular replicative intermediate HBV DNA, the MxA exerted some
      antiviral activities as it effectively suppressed the secretion of HBsAg and
      HBeAg in HepG2.2.15 cells. CONCLUSIONS: HBV and its antigen components probably
      influence the expression of antiviral proteins. IFN- resistance may be related to
      the down-regulation of antiviral proteins expression.

PMID- 22409853
TI  - [The expression and significance of signal regulatory protein a1 in autoimmune
      hepatitis].
AB  - OBJECTIVE: To observe the expression change of signal regulatory protein alpha1
      (SIRPalpha1) in autoimmune hepatitis (AIH) and approach the relationship between
      SIRPalpha1 and the extent of inflammation. METHODS: Immunohistochemistry is used
      to detect the expression of SIRPalpha1 in the paraffin section preparations of 33
      AIH and 10 normal hepatic tissue. RESULTS: SIRPalpha1 is positive or weakly
      positive expressed in AIH. The staining is localized in the cytoplasm of Kupffer
      cells in the hepatic sinusoid with focal distribution. It is negative in normal
      hepatic tissue. In light AIH, it is negative or weakly positive expressed with a
      36.4 percent of the positive rate (4/11). The positive or strong positive
      expression is found in the moderate AIH with an 84.2 percent of the positive
      rate(16/19). There is statistical significance between both light AIH, moderate
      AIH and severe AIH (P less than 0.001) and moderate AIH and light AIH (P less
      than 0.001). There is no statistical significance between both light AIH and
      severe AIH (P = 0.145 ) and moderate AIH and severe AIH (P = 0.084). CONCLUSIONS:
      As a negative regulatory factor, the expression of SIRPalpha1 in hepatic sinusoid
      Kupffer cells is some associated with the extent of AIH.

PMID- 22409854
TI  - [Validation of transient elastography (Fibroscan) in assessment of hepatic
      fibrosis in autoimmune hepatitis].
AB  - OBJECTIVE: To validate transient elastography (Fibroscan) in assessment of
      hepatic fibrosis in autoimmune hepatitis (AIH). METHODS: Liver stiffness was
      assessed using Fibroscan in totally 30 patients with AIH. We compared the results
      of Fibroscan with the Scheuer fibrosis stage in liver biopsy in each patient.
      RESULTS: 4 patients were shown as liver fibrosis stage S0, 6 as S1, 5 as S2, 11
      as S3 and 4 as S4. Failure of the Fibroscan measurement occurred in 1 case (3.3%)
      because of her increased body mass index (BMI). The stiffness of Fibroscan was
      significantly correlated with the liver biopsy fibrosis stage (r = 0.801, P less
      than 0.001). The liver stiffnesses between mild and moderate fibrosis (S0-2) and
      advanced fibrosis (S3-4) were significantly different (t = -3.937, P = 0.001).
      CONCLUSION: Transient elastography (Fibroscan) is a promising non-invasive method
      for detection of fibrosis in patients with autoimmune hepatitis. Its use for the
      follow up and management of these patients and should be evaluated further.

PMID- 22409855
TI  - Pain processing by spinal microcircuits: afferent combinatorics.
AB  - Pain, itch, heat, cold, and touch represent different percepts arising from
      somatosensory input. How stimuli give rise to these percepts has been debated for
      over a century. Recent work supports the view that primary afferents are highly
      specialized to transduce and encode specific stimulus modalities. However, cross
      modal interactions (e.g. inhibition or exacerbation of pain by touch) support
      convergence rather than specificity in central circuits. We outline how
      peripheral specialization together with central convergence could enable spinal
      microcircuits to combine inputs from distinctly specialized, co-activated
      afferents and to modulate the output signals thus formed through computations
      like normalization. These issues will be discussed alongside recent advances in
      our understanding of microcircuitry in the superficial dorsal horn.

PMID- 22409856
TI  - Synaptopathies: diseases of the synaptome.
AB  - The human synapse proteome is a highly complex collection of proteins that is
      disrupted by hundreds of gene mutations causing over 100 brain diseases. These
      synaptic diseases, or synaptopathies, cause major psychiatric, neurological and
      childhood developmental disorders through mendelian and complex genetic
      mechanisms. The human postsynaptic proteome and its core signaling complexes
      built by the assembly of receptors and enzymes around Membrane Associated
      Guanylate Kinase (MAGUK) scaffold proteins are a paradigm for systematic analysis
      of synaptic diseases. In humans, the MAGUK Associated Signaling Complexes are
      mutated in Autism, Schizophrenia, Intellectual Disability and many other
      diseases, and mice carrying orthologous mutations show relevant cognitive,
      social, motoric and other phenotypes. Diseases with similar phenotypes and
      symptom spectrums arise from disruption of complexes and interacting proteins
      within the synapse proteome. Classifying synaptic disease phenotypes with genetic
      and proteome data provides a new brain disease classification system based on
      molecular etiology and pathogenesis.

PMID- 22409857
TI  - Conventional epidemiology underestimates the incidence of asthma and wheeze-a
      longitudinal population-based study among teenagers.
AB  - BACKGROUND: Because of shifts in the gender ratio and incidence and remission
      rates of asthma during the teen ages, the methodology of incidence studies among
      teenagers is important, i.e. if the time intervals between surveys are too long,
      the incident cases might not be properly identified. The aim was to study the
      impact of study design on the incidence rates of asthma and wheeze during the
      teen ages. METHODS: In a study about asthma and allergic diseases within the OLIN
      studies (Obstructive Lung Disease in northern Sweden), a cohort of school
      children (n = 3,430) was followed annually by questionnaire from age 8 yrs. In
      the endpoint survey (age 18 yrs) 2,582 (75% of original responders) participated.
      Incident cases from age 12-18 yrs were identified by two methods: annual
      questionnaire reports (AR) and baseline-endpoint surveys only (BE). RESULTS: The
      cumulative incidence of asthma and wheeze was significantly higher based on AR
      compared to BE. Compared to the incidence rates based on all the annual surveys,
      the calculated average annual rates based on BE were in general lower both among
      the boys and among the girls. There were no differences between boys and girls in
      incidence rates of asthma or wheeze during the early teen years. However, from
      the age of 15 years, the annual incidence rates were significantly or borderline
      significantly higher among girls than boys. At onset, the additional cases of
      current asthma identified by AR had significantly less severe asthma than those
      identified in BE (p < 0.02). CONCLUSION: the size of the incidence of asthma and
      wheeze during the teen ages was influenced by study design. By using the
      conventional prospective study design with longer follow-up time, the incidence
      was underestimated.

PMID- 22409858
TI  - Variation in thromboembolic complications among patients undergoing commonly
      performed cancer operations.
AB  - OBJECTIVE: There is widespread evidence that cancer confers an increased risk of
      deep venous thrombosis (DVT). This risk is thought to vary among different cancer
      types. The purpose of this study is to better define the incidence of thrombotic
      complications among patients undergoing surgical treatment for a spectrum of
      prevalent cancer diagnoses in contemporary practice. METHODS: All patients
      undergoing one of 11 cancer surgical operations (breast resection, hysterectomy,
      prostatectomy, colectomy, gastrectomy, lung resection, hepatectomy,
      pancreatectomy, cystectomy, esophagectomy, and nephrectomy) were identified by
      Current Procedural Terminology and International Classification of Diseases,
      Ninth Revision codes using the American College of Surgeons National Surgical
      Quality Improvement Program database (2007-2009). The study endpoints were DVT,
      pulmonary embolism (PE), and overall postoperative venous thromboembolic events
      (VTE) within 1 month of the index procedure. Multivariate logistic regression was
      utilized to calculate adjusted odds ratios for each endpoint. RESULTS: Over the
      study interval, 43,808 of the selected cancer operations were performed. The
      incidence of DVT, PE, and total VTE within 1 month following surgery varied
      widely across a spectrum of cancer diagnoses, ranging from 0.19%, 0.12%, and
      0.28% for breast resection to 6.1%, 2.4%, and 7.3%, respectively, for
      esophagectomy. Compared with breast cancer, the incidence of VTE ranged from a
      1.31-fold increase in VTE associated with gastrectomy (95% confidence interval,
      0.73-2.37; P = .4) to a 2.68-fold increase associated with hysterectomy (95%
      confidence interval, 1.43-5.01; P = .002). Multivariate logistic regression
      revealed that inpatient status, steroid use, advanced age (>=60 years), morbid
      obesity (body mass index >=35), blood transfusion, reintubation, cardiac arrest,
      postoperative infectious complications, and prolonged hospitalization were
      independently associated with increased risk of VTE. CONCLUSIONS: The incidence
      of VTE and thromboembolic complications associated with cancer surgery varies
      substantially. These findings suggest that both tumor type and resection
      magnitude may impact VTE risk. Accordingly, such data support diagnosis and
      procedural-specific guidelines for perioperative VTE prophylaxis and can be used
      to anticipate the risk of potentially preventable morbidity.

PMID- 22409859
TI  - Judgments about moral responsibility and determinism in patients with behavioural
      variant of frontotemporal dementia: still compatibilists.
AB  - Do laypeople think that moral responsibility is compatible with determinism?
      Recently, philosophers and psychologists trying to answer this question have
      found contradictory results: while some experiments reveal people to have
      compatibilist intuitions, others suggest that people could in fact be
      incompatibilist. To account for this contradictory answers, Nichols and Knobe
      (2007) have advanced a 'performance error model' according to which people are
      genuine incompatibilist that are sometimes biased to give compatibilist answers
      by emotional reactions. To test for this hypothesis, we investigated intuitions
      about determinism and moral responsibility in patients suffering from behavioural
      frontotemporal dementia. Patients suffering from bvFTD have impoverished
      emotional reaction. Thus, the 'performance error model' should predict that bvFTD
      patients will give less compatibilist answers. However, we found that bvFTD
      patients give answers quite similar to subjects in control group and were mostly
      compatibilist. Thus, we conclude that the 'performance error model' should be
      abandoned in favour of other available model that best fit our data.

PMID- 22409860
TI  - Amphiregulin and Epiregulin mRNA expression in primary colorectal cancer and
      corresponding liver metastases.
AB  - BACKGROUND: Amphiregulin (AREG) and Epiregulin (EREG), ligands of EGFR, are
      reported to be predictive biomarkers of colorectal cancer patients treated with
      Cetuximab, an anti-EGFR antibody. The purpose of this study is to determine the
      correlation of AREG and EREG expression between primary colorectal cancer and
      corresponding liver metastases. METHODS: One hundred twenty colorectal cancer
      patients with liver metastases (100 with synchronous metastases, 20 with
      metachronous) were evaluated. No patients had ever received anti-EGFR antibody
      agents. AREG and EREG mRNA expression from both the primary tumor and liver
      metastases were measured using real-time RT-PCR. KRAS codon 12, 13 mutation
      status was analyzed by direct sequencing. RESULTS: Modest, but significant,
      correlations were observed between primary tumor and corresponding liver
      metastases in both AREG mRNA expression (Rs = 0.54, p < 0.0001) and EREG mRNA
      expression (Rs = 0.58, p < 0.0001). AREG and EREG mRNA expression was strongly
      correlated in both the primary tumor (Rs = 0.81, p < 0.0001) and the liver
      metastases (Rs = 0.87, p < 0.0001). No significant survival difference was
      observed between low and high AREG or EREG patients when all 120 patients were
      analyzed. However, when divided by KRAS status, KRAS wild-type patients with low
      EREG mRNA levels in the primary site showed significantly better overall survival
      rates than those with high levels (p = 0.018). In multivariate analysis, low EREG
      expression was significantly associated with better overall survival (p = 0.006).
      CONCLUSIONS: AREG and EREG expression showed a modest correlation between primary
      tumor and liver metastases. As EREG mRNA expression was associated with decreased
      survival, it is appeared to be a useful prognostic marker in KRAS wild-type
      patients who never received anti-EGFR therapy.

PMID- 22409861
TI  - Healthcare costs and productivity losses directly attributable to ankylosing
      spondylitis.
AB  - OBJECTIVES: To describe the healthcare resource use and productivity losses
      associated with patients with ankylosing spondylitis (AS) and explore the
      relationship between disease severity and total costs. METHODS: A cross-sectional
      postal survey was conducted on a sample of 1,000 patients with AS randomly
      selected from registries at 10 secondary care rheumatology centres in the UK.
      Information on demographic characteristics, disease and functional activity,
      healthcare use and work status (presenteeism and absenteeism) during the previous
      three months was collected. The relationship between disease severity and total
      costs was explored using a two-part regression model, controlling for age, gender
      and disease duration and validated on respondents (n=470) of the second round of
      the survey. RESULTS: Respondents at baseline (n=612) covered the full spectrum of
      AS, had a mean BASDAI of 4.6 and 55.3% of individuals scored at least 4 on the
      BASDAI scale. The mean (median) three month total cost was L2,802 (L1,160). Both
      physical function and disease activity were significant predictors of total
      costs. Mean (median) three month total costs for patients with BASDAI <4, 4-6 and
      >6 were L1,331 (L502), L2,790 (L1,281) and L4,840 (L5,017) respectively. Direct
      National Health Service funded healthcare costs contributed to just 15% of total
      costs while unemployment, absenteeism from work and reduced productivity at work
      accounted for 63.2%, 1.4% and 19.0% of total costs, respectively. CONCLUSIONS:
      This study shows that direct healthcare costs alone do not describe the total
      costs associated with AS and that productivity losses associated with AS are
      considerable.

PMID- 22409862
TI  - Development of novel immune interventions for prostate cancer.
AB  - Prostate cancer is the leading cause of cancer-related morbidity and mortality in
      men in the Western world. Use of traditional and newer therapeutic regimens is
      constrained in terms of tolerance, efficacy, and cross-resistance. There is a
      need for newer therapies without overlapping mechanisms of action and toxicities
      to improve the outcome. Advances in the field of immunology and cancer biology
      have led to an improved understanding of the interactions between the immune
      system and tumors, propelling the field of cancer vaccines to the forefront of
      clinical investigation. Recent US Food and Drug Administration approval of
      sipuleucel-T, an autologous dendritic cell-based vaccine for the treatment of
      castration refractory prostate cancer, represents a significant advancement in
      the field of cancer vaccines. However, the overall survival benefits with
      sipuleucel-T are modest at best, and the field of cancer vaccine therapy is in a
      continuous state of evolution and expansion. Further improvements are expected to
      result from the selection of more appropriate tumor antigens, which circumvent
      immune tolerance, and from the development of more effective immunization
      strategies aimed at inducing an effective cytotoxic T-cell response. This review
      summarizes recent developments in the field of immunotherapy in prostate cancer
      with a focus on dendritic cell vaccines, virus-based vaccines, DNA-based
      vaccines, cell-based vaccines, peptide-based vaccine and therapies blocking
      immune checkpoints to break peripheral immune tolerance.

PMID- 22409863
TI  - A primary signet ring cell carcinoma of the prostate with bone metastasis with
      impressive response to FOLFOX and cetuximab.

PMID- 22409864
TI  - Response of metastatic renal medullary carcinoma to carboplatinum and Paclitaxel
      chemotherapy.

PMID- 22409865
TI  - Spontaneous regression of thoracic metastases while progression of brain
      metastases after stereotactic radiosurgery and stereotactic body radiotherapy for
      metastatic renal cell carcinoma: abscopal effect prevented by the blood-brain
      barrier?

PMID- 22409866
TI  - Welcome to clinical and translational allergy.

PMID- 22409867
TI  - Targeted therapies for advanced non-small cell lung cancer.
AB  - The incorporation of targeted agents has considerably improved the management of
      patients with advanced non-small cell lung cancer (NSCLC) over the last years.
      The main targets include the epidermal growth factor receptor (EGFR) and the
      vascular endothelial growth factor (VEGF). Currently available agents with
      established role in NSCLC include the anti-EGFR tyrosine-kinase inhibitors (TKIs)
      erlotinib/gefitinib and the anti-VEGF monoclonal antibody bevacizumab. Moreover,
      several other agents targeting critical pathways in lung carcinogenesis are
      currently under preclinical or clinical evaluation. This review presents an
      update on the role of targeted agents in advanced NSCLC. In addition, we present
      the main clinical studies investigating the activity of these agents in NSCLC and
      we provide recent data with respect to future therapeutic strategies.

PMID- 22409868
TI  - Bioenergetic role of mitochondrial fusion and fission.
AB  - Mitochondria are highly dynamic organelles. Frequent cycles of fusion and fission
      adapt the morphology of the mitochondrial compartment to the metabolic needs of
      the cell. Mitochondrial fusion is particularly important in respiratory active
      cells. It allows the spreading of metabolites, enzymes, and mitochondrial gene
      products throughout the entire mitochondrial compartment. This serves to optimize
      mitochondrial function and counteracts the accumulation of mitochondrial
      mutations during aging. Fragmented mitochondria are frequently found in resting
      cells, and mitochondrial fission plays an important role in the removal of
      damaged organelles by autophagy. Thus, mitochondrial fusion and fission both
      contribute to maintenance of mitochondrial function and optimize bioenergetic
      capacity. Multiple signalling pathways regulate the machinery of mitochondrial
      dynamics to adapt the shape of the mitochondrial compartment to the metabolic
      conditions of the cell. This article is part of a Special Issue entitled: 17th
      European Bioenergetics Conference (EBEC 2012).

PMID- 22409869
TI  - Policy and programmatic implications of task shifting in Uganda: a case study.
AB  - BACKGROUND: Uganda has a severe health worker shortage and a high demand for
      health care services. This study aimed to assess the policy and programmatic
      implications of task shifting in Uganda. METHODS: This was a qualitative,
      descriptive study through 34 key informant interviews and eight (8) focus group
      discussions, with participants from various levels of the health system. RESULTS:
      Policy makers understood task shifting, but front-line health workers had
      misconceptions on the meaning and intention(s) of task shifting. Examples were
      cited of task shifting within the Ugandan health system, some formalized (e.g.
      psychiatric clinical officers), and some informal ones (e.g. nurses inserting IV
      lines and initiating treatment). There was apparently high acceptance of task
      shifting in HIV/AIDS service delivery, with involvement of community health
      workers (CHW) and PLWHA in care and support of AIDS patients.There was no written
      policy or guidelines on task shifting, but the policy environment was reportedly
      conducive with plans to develop a policy and guidelines on task shifting.Factors
      favouring task shifting included successful examples of task shifting, proper
      referral channels, the need for services, scarcity of skills and focused
      initiatives such as home based management of fever. Barriers to task shifting
      included reluctance to change, protection of professional turf, professional
      boundaries and regulations, heavy workload and high disease burden, poor
      planning, lack of a task shifting champion, lack of guidelines, the name task
      shifting itself, and unemployed health professionals.There were both positive and
      negative views on task shifting: the positive ones cast task shifting as one of
      the solutions to the dual problem of lack of skills and high demand for service,
      and as something that is already happening; while negative ones saw it as a quick
      fix intended for the poor, a threat to quality care and likely to compromise the
      health system. CONCLUSION: There were widespread examples of task in Uganda, and
      task shifting was mainly attributed to HRH shortages coupled with the high demand
      for healthcare services. There is need for clear policy and guidelines to
      regulate task shifting and protect those who undertake delegated tasks.

PMID- 22409870
TI  - Direct plasma metabolite analysis of positron emission tomography radioligands by
      micellar liquid chromatography with radiometric detection.
AB  - Determination of radio-metabolites in plasma samples taken during a positron
      emission tomography (PET) study is an important component in the pharmacokinetic
      evaluation of PET radioligands. We have developed and validated a new analytical
      procedure for the plasma metabolite analysis of PET radioligands based on
      micellar liquid chromatography using an anionic surfactant mobile phase.
      Chromatographic separation was performed on an octadecyl semipreparative column
      (10 mm I.D. * 160 mm, 10 MUm) using 100 mM sodium dodecyl sulfate (SDS) and 1
      butanol in 10 mM sodium-phosphate (pH 7.2) at a flow rate of 5 mL/min. The
      samples taken from monkey or human plasma during PET measurements were directly
      injected into a liquid chromatographic (LC) system coupled to an online
      radiometric detector under micellar conditions using 1-2% (v/v) 1-butanol mobile
      phase to remove plasma proteins and concentrate the analytes at the column head.
      At 2 min, mobile phase was changed to elute and separate PET radioligand and its
      radiometabolites with high peak capacity under high submicellar conditions (10
      25% 1-butanol). This procedure allowed direct plasma injection (up to 2 mL) into
      the LC column without any pretreatment with a short analysis-time of 8-10 min.
      Satisfactory reproducibility, linearity, sensitivity, accuracy and recovery were
      obtained in the validation study. The developed method was successfully applied
      to study the metabolism for diverse groups of PET radioligands and provided
      reliable determination of PET radioligands in human and monkey plasma. This
      method is advantageous in terms of simplifying and shortening the processes
      required to analyze short-lived radioligands as well as in providing a more
      accurate estimation of the metabolite corrected input function, especially for
      the radioligands with lower recoveries or degradation potential during the
      deproteination process in a conventional procedure.

PMID- 22409871
TI  - X-ray diffraction, IR spectroscopy and thermal characterization of partially
      hydrolyzed guar gum.
AB  - Guar gum was hydrolyzed using cellulase from Aspergillus niger at 5.6 pH and 50
      degrees C temperature. Hydrolyzed guar gum sample was characterized using Fourier
      transform infrared spectroscopy, differential scanning calorimetry,
      thermogravimetric analysis, X-ray diffraction, dilute solution viscometry and
      rotational viscometry. Viscometry analysis of native guar gum showed a molecular
      weight of 889742.06, whereas, after enzymatic hydrolysis, the resultant product
      had a molecular weight of 7936.5. IR spectral analysis suggests that after
      enzymatic hydrolysis of guar gum there was no major transformation of functional
      group. Thermal analysis revealed no major change in thermal behavior of
      hydrolyzed guar gum. It was shown that partial hydrolysis of guar gum could be
      achieved by inexpensive and food grade cellulase (Aspergillus niger) having
      commercial importance and utilization as a functional soluble dietary fiber for
      food industry.

PMID- 22409872
TI  - In vitro characterization and osteoblast responses to nanostructured
      photocatalytic TiO2 coated surfaces.
AB  - The aims of the study were to characterize a nanostructured photoactive titanium
      dioxide (TiO(2)) coating and to compare the cellular response of human
      osteoblasts before and after ultraviolet (UV) irradiation of the coating. A
      specific nanostructured TiO(2) powder (Degussa P-25), which consists of
      approximately 80% anatase and 20% rutile, was spin-coated onto commercially pure
      titanium discs, and was heat-treated thereafter. After topographical, chemical
      and photocatalytic property characterizations, human osteoblasts were cultured on
      the coated discs before and after UV irradiation. Cell morphology was evaluated
      by scanning electron microscopy (SEM), and cell viability was analysed by 3-(4,5
      dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay. From the contact
      angle analysis, the wettability significantly improved after UV irradiation. The
      cultured cells were flattened with numerous elongated lammellipodia; however, no
      morphological differences were indicated between -UV and +UV surfaces. The MTT
      assay analysis showed that -UV surface presented significantly higher viability
      compared to the +UV surface except for one cell population group at 3h where
      there were no differences. The nanostructured photoactive TiO(2) surface improved
      its hydrophilicity by UV irradiation, however no enhancing effect in cell
      response was confirmed at the time tested compared to the non-irradiated surface.

PMID- 22409873
TI  - Physical characterization and osteogenic activity of the quaternized chitosan
      loaded PMMA bone cement.
AB  - Gentamicin-loaded polymethylmethacrylate (PMMA), widely used for primary cemented
      arthroplasty and revision surgery for preventing or treating infections, may lead
      to the evolution of antibiotic-resistant bacteria and dysfunction of osteogenic
      cells, which further influence the osteointegration of bone cement. In a previous
      study, we reported that a new quaternized chitosan derivative
      (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) that was loaded into
      PMMA significantly inhibited the formation of biofilms caused by methicillin
      resistant Staphylococcus strains. In the present study, we further investigated
      the surface morphology, hydrophilicity, apatite formation ability and osteogenic
      activity of HACC-loaded PMMA. Chitosan-loaded PMMA, gentamicin-loaded PMMA and
      PMMA without antibiotic were also investigated and compared. The results showed
      that, compared to other PMMA-based cements, HACC-loaded PMMA had improved
      properties such as a lower polymerization temperature, prolonged setting time,
      porous structures after immersion in phosphate-buffered saline, higher
      hydrophilicity, more apatite formation on the surface after immersion in
      simulated body fluid, and better attachment and spreading of the human-marrow
      derived mesenchymal stem cells. We also found better stem cell proliferation,
      osteogenic differentiation, and osteogenesis-associated genes expression on the
      surface of the HACC-loaded PMMA compared to the gentamicin-loaded PMMA.
      Therefore, this new anti-infective bone cement had improved physical properties
      and osteogenic activity, which may lead to better osteointegration of the bone
      cement in cemented arthroplasty.

PMID- 22409874
TI  - The stimulation of proliferation and differentiation of periodontal ligament
      cells by the ionic products from Ca7Si2P2O16 bioceramics.
AB  - The ultimate goal of periodontal tissue engineering is to produce predictable
      regeneration of alveolar bone, root cementum, and periodontal ligament, which are
      lost as a result of periodontal diseases. To achieve this goal, it is of great
      importance to develop novel bioactive materials which could stimulate the
      proliferation, differentiation and osteogenic/cementogenic gene expression of
      periodontal ligament cells (PDLCs) for periodontal regeneration. In this study,
      we synthesized novel Ca(7)Si(2)P(2)O(16) ceramic powders for the first time by
      the sol-gel method and investigated the biological performance of PDLCs after
      exposure to different concentrations of Ca(7)Si(2)P(2)O(16) extracts. The
      original extracts were prepared at 200 mg ml(-1) and further diluted with serum
      free cell culture medium to obtain a series of diluted extracts (100, 50, 25,
      12.5 and 6.25 mg ml(-1)). Proliferation, alkaline phosphatase (ALP) activity, Ca
      deposition, and osteogenesis/cementogenesis-related gene expression (ALP, Col I,
      Runx2 and CEMP1) were assayed for PDLCs on days 7 and 14. The results showed that
      the ionic products from Ca(7)Si(2)P(2)O(16) powders significantly stimulated the
      proliferation, ALP activity, Ca deposition and osteogenesis/cementogenesis
      related gene expression of PDLCs. In addition, it was found that
      Ca(7)Si(2)P(2)O(16) powders had excellent apatite-mineralization ability in
      simulated body fluids. This study demonstrated that Ca(7)Si(2)P(2)O(16) powders
      with such a specific composition possess the ability to stimulate the PDLC
      proliferation and osteoblast/cemenoblast-like cell differentiation, indicating
      that they are a promising bioactive material for periodontal tissue regeneration
      application.

PMID- 22409875
TI  - Phase composition and in vitro bioactivity of porous implants made of bioactive
      glass S53P4.
AB  - This work studied the influence of sintering temperature on the phase
      composition, compression strength and in vitro properties of implants made of
      bioactive glass S53P4. The implants were sintered within the temperature range
      600-1000 degrees C. Over the whole temperature range studied, consolidation took
      place mainly via viscous flow sintering, even though there was partial surface
      crystallization. The mechanical strength of the implants was low but increased
      with the sintering temperature, from 0.7 MPa at 635 degrees C to 10 MPa at 1000
      degrees C. Changes in the composition of simulated body fluid (SBF), the
      immersion solution, were evaluated by pH measurements and ion analysis using
      inductively coupled plasma optical emission spectrometry. The development of a
      calcium phosphate layer on the implant surfaces was verified using scanning
      electron microscopy-electron-dispersive X-ray analysis. When immersed in SBF, a
      calcium phosphate layer formed on all the samples, but the structure of this
      layer was affected by the surface crystalline phases. Hydroxyapatite formed more
      readily on amorphous and partially crystalline implants containing both primary
      Na(2)O.CaO.2SiO(2) and secondary Na(2)Ca(4)(PO(4))(2)SiO(4) crystals than on
      implants containing only primary crystals.

PMID- 22409876
TI  - Capilia test for identification of Mycobacterium tuberculosis in MGITTM-positive
      cultures.
AB  - BACKGROUND: The performance of the Capilia test for rapid identification of
      Mycobacterium tuberculosis complex (MTC) in Mycobacterium Growth Indicator Tube
      (MGIT) positive samples with contaminating organisms is not well documented.
      OBJECTIVE: To assess the diagnostic yield  of the Capilia test in the rapid
      identification of MTC in MGIT-positive cultures. DESIGN: A total of 459 selected
      sputum samples were cultured using BACTECTM MGITTM 960. Tubes flagged positive by
      the MGIT instrument (MGIT-positive) were examined for acid-fast bacilli and
      cording  in smears, spotted on blood agar (BA), subcultured for biochemical tests
      and tested using the Capilia test. Based on smear and growth on BA, MGIT-positive
      tubes were grouped into MGIT true-positive, MGIT-positive with contamination and
      MGIT contamination. Performance parameters of Capilia  test such as sensitivity,
      specificity, efficiency, and positive and negative predictive values (PPV, NPV)
      for each of these groups were determined against biochemical tests as gold
      standard. RESULTS: Of the 346 MGIT-positives, respectively 233, 73 and 40 were
      MGIT true-positive, MGIT-positive  with contamination and MGIT contamination. For
      the three groups, the PPV and NPV of the Capilia test were respectively 97%, 96%
      and 100%, and 32%, 27% and 60%. CONCLUSION: In settings with high contamination
      of MGIT cultures, the performance of the Capilia test is diminished.

PMID- 22409877
TI  - A systematic review of the clinical effectiveness and cost-effectiveness of
      Pharmalgen(r) for the treatment of bee and wasp venom allergy.
AB  - BACKGROUND: Each year in the UK, there are between two and nine deaths from
      anaphylaxis caused by bee and wasp venom. Anaphylactic reactions can occur
      rapidly following a sting and can progress to a life-threatening condition within
      minutes. To avoid further reactions in people with a history of anaphylaxis to
      bee and wasp venom, the use of desensitisation, through a process known as venom
      immunotherapy (VIT), has been investigated and is in use in the UK. VIT consists
      of subcutaneous injections of increasing amounts of purified bee and/or wasp
      venom extract. Pharmalgen(r) products (ALK Abello) have had UK marketing
      authorisation for VIT (as well as diagnosis) of allergy to bee venom (using
      Pharmalgen Bee Venom) and wasp venom (using Pharmalgen Wasp Venom) since March
      1995. OBJECTIVE: This review assessed the clinical effectiveness and cost
      effectiveness of Pharmalgen in providing immunotherapy to individuals with a
      history of type 1 [immunoglobulin E (IgE)-mediated] systemic allergic reaction to
      bee and wasp venom. DATA SOURCES: A comprehensive search strategy using a
      combination of index terms (e.g. Pharmalgen) and free-text words (e.g. allerg$)
      was developed and used to interrogate the following electronic databases: EMBASE,
      MEDLINE, The Cochrane Library. REVIEW METHODS: Papers were included if they
      studied venom immunotherapy using Pharmalgen (PhVIT) in patients who had
      previously experienced a systemic reaction to a bee and/or a wasp sting.
      Comparators were any alternative treatment options available in the NHS without
      VIT. Included outcomes were systemic reactions, local reactions, mortality,
      anxiety related to the possibility of future allergic reactions, health-related
      quality of life (QoL) and adverse reactions (ARs) to treatment. Cost
      effectiveness outcomes included cost per quality-adjusted life-years (QALYs)
      gained. Because of the small number of published randomised controlled trials
      (RCTs), no meta-analyses were conducted. A de novo economic model was developed
      to assess the cost-effectiveness of PhVIT plus high-dose antihistamine (HDA) plus
      adrenaline auto-injector (AAI) plus avoidance advice in relation to two
      comparators. RESULTS: A total of 1065 citations were identified, of which 266
      full-text papers were obtained. No studies were identified that compared PhVIT
      with any of the outlined comparators. When these criteria were widened to include
      different protocols and types of PhVIT administration, four RCTs and five quasi
      experimental studies were identified for inclusion. The quality of included
      studies was poor, and none was conducted in the UK. Eight studies reported re
      sting data (systemic reactions ranged from 0.0% to 36.4%) and ARs (systemic
      reactions ranged from 0.0% to 38.1% and none was fatal). No included studies
      reported quality of life. No published economic evidence relevant to the decision
      problem was identified. The manufacturer of PhVIT did not submit any clinical
      effectiveness or cost-effectiveness evidence to the National Institute for Health
      and Clinical Excellence in support of PhVIT. The results of the Assessment
      Group's (AG) base-case analysis show that the comparison of PhVIT + HDA + AAI
      versus AAI + HDA yields an incremental cost-effectiveness ratio (ICER) of
      L18,065,527 per QALY gained; PhVIT + HDA + AAI versus avoidance advice only
      yields an ICER of L7,627,835 per QALY gained. The results of the sensitivity
      analyses and scenario analyses showed that the results of the base-case economic
      evaluation were robust for every plausible change in parameter made. The results
      of the 'High Risk of Sting Patients' subgroup analysis show that PhVIT + HDA +
      AAI dominates both AAI + HDA and avoidance advice only (i.e. is less expensive
      and more effective). The 'VIT Anxiety QoL Improvement' subgroup analysis shows
      that PhVIT + HDA + AAI versus HDA + AAI has an ICER of L23,868 per QALY gained,
      and PhVIT + HDA + AAI versus avoidance advice only yields an ICER of L25,661 per
      QALY gained. LIMITATIONS: This review is limited to the use of Pharmalgen in the
      treatment of hymenoptera venom allergy and therefore does not assess the
      effectiveness of VIT in general. CONCLUSIONS: The current use of PhVIT in
      clinical practice in the NHS appears to be based on limited and poor-quality
      clinical effectiveness research. Available evidence indicates that sting
      reactions following the use of PhVIT are low and that the ARs related to
      treatment are minor and easily treatable. The results of the AG's de novo
      economic evaluation demonstrate that PhVIT + AAI + HDA compared with AAI + HDA
      and with avoidance advice only yields ICERs in the range of L8-20M per QALY
      gained. Two subgroups ('High Risk of Sting Patients' and 'VIT Anxiety QoL
      Improvement') were considered in the economic evaluation and the AG concludes
      that the use of PhVIT + AAI + HDA may be cost-effective in both groups. Future
      research should focus on clearly identifying groups of patients most likely to
      benefit from treatment and ensure that clinical practice is focussed on these
      groups. Furthermore, given the paucity of UK data in this area it would be
      informative if data could be collected routinely when VIT is administered in the
      NHS (e.g. rates of systemic adverse reactions to VIT, rates of systemic reactions
      to bee/wasp stings). FUNDING: The National Institute for Health Research Health
      Technology Assessment programme.

PMID- 22409878
TI  - Characterization of the antiproliferative activity of Xylopia aethiopica.
AB  - BACKGROUND: Xylopia aethiopica, a plant found throughout West Africa, has both
      nutritional and medicinal uses. The present study aims to characterize the
      effects of extracts of this plant on cancer cells. RESULTS: We report that X.
      aethiopica extract prepared with 70% ethanol has antiproliferative activity
      against a panel of cancer cell lines. The IC50 was estimated at 12 MUg/ml against
      HCT116 colon cancer cells, 7.5 MUg/ml and > 25 MUg/ml against U937 and KG1a
      leukemia cells, respectively. Upon fractionation of the extract by HPLC, the
      active fraction induced DNA damage, cell cycle arrest in G1 phase and apoptotic
      cell death. By using NMR and mass spectrometry, we determined the structure of
      the active natural product in the HPLC fraction as ent-15-oxokaur-16-en-19-oic
      acid. CONCLUSION: The main cytotoxic and DNA-damaging compound in ethanolic
      extracts of Xylopia aethiopica is ent-15-oxokaur-16-en-19-oic acid.

PMID- 22409879
TI  - Mechanisms of allergen-specific immunotherapy.
AB  - Allergen-specific immunotherapy (allergen-SIT) is a potentially curative
      treatment approach in allergic diseases. It has been used for almost 100 years as
      a desensitizing therapy. The induction of peripheral T cell tolerance and
      promotion of the formation of regulatory T-cells are key mechanisms in allergen
      SIT. Both FOXP3+CD4+CD25+ regulatory T (Treg) cells and inducible IL-10- and TGF
      beta-producing type 1 Treg (Tr1) cells may prevent the development of allergic
      diseases and play a role in successful allergen-SIT and healthy immune response
      via several mechanisms. The mechanisms of suppression of different pro
      inflammatory cells, such as eosinophils, mast cells and basophils and the
      development of allergen tolerance also directly or indirectly involves Treg
      cells. Furthermore, the formation of non-inflammatory antibodies particularly
      IgG4 is induced by IL-10. Knowledge of these molecular basis is crucial in the
      understanding the regulation of immune responses and their possible therapeutic
      targets in allergic diseases.

PMID- 22409880
TI  - Ultrasonographic measures of synovitis in an early phase clinical trial: a double
      blind, randomised, placebo and comparator controlled phase IIa trial of GW274150
      (a selective inducible nitric oxide synthase inhibitor) in rheumatoid arthritis.
AB  - OBJECTIVES: To test the sensitivity to change of ultrasonographic endpoints in
      early phase clinical trials in subjects with active rheumatoid arthritis (RA).
      METHODS: A double-blind, placebo and comparator controlled, randomised, two
      centre study investigated the effect on synovial thickness and vascularity of 28
      days repeat daily oral dosing of 60 mg of the inducible nitric oxide synthase
      inhibitor GW274150 or 7.5 mg prednisolone in RA. Fifty patients with DAS28 scores
      >=4.0 were assigned to 3 treatment arms of 17, 19 and 14 (on placebo, GW274150
      and prednisolone respectively). Synovial thickness and vascularity of all 10
      metacarpophalangeal joints were assessed by ultrasonography using a semi
      quantitative scale at baseline (Day 1), Day 15 and Day 28. Vascularity was also
      measured quantitatively by power Doppler area. RESULTS: At Day 28, the GW274150
      group showed a trend towards reduction in synovial thickness compared with
      placebo, with an adjusted mean decrease of 33% (p=0.072); the prednisolone group
      decreased significantly by 44% (p=0.011). Similarly, there was a trend to reduced
      synovial vascularity with GW274150 by 42% compared with placebo (p=0.075);
      prednisolone resulted in a statistically significant decrease of 55% (p=0.012).
      There was a 55% decrease in power Doppler area for GW274150, compared with
      placebo although the result was not statistically significant (p=0.375).
      Prednisolone 7.5 mg resulted in a highly statistically significant decrease of
      95% (p=0.003). CONCLUSIONS: This study advocates the use of ultrasonographic
      measures of metacarpophalangeal joint synovitis as an endpoint for clinical
      studies assessing therapeutic potential of new compounds in small patient cohorts
      over 28 days.

PMID- 22409881
TI  - The model of Palliative Care in the perinatal setting: a review of the
      literature.
AB  - BACKGROUND: The notion of Palliative Care (PC) in neonatal and perinatal medicine
      has largely developed in recent decades. Our aim was to systematically review the
      literature on this topic, summarise the evolution of care and, based on the
      available data, suggest a current standard for this type of care. METHODS: Data
      sources included Medline, the Cochrane Library, CINAHL, and the bibliographies of
      the papers retrieved. Articles focusing on neonatal/perinatal hospices or PC were
      included. A qualitative analysis of the content was performed, and data on the
      lead author, country, year, type of article or design, and direct and indirect
      subjects were obtained. RESULTS: Among the 1558 articles retrieved, we did not
      find a single quantitative empirical study. To study the evolution of the model
      of care, we ultimately included 101 studies, most of which were from the USA.
      Fifty of these were comments/reflections, and only 30 were classifiable as
      clinical studies (half of these were case reports). The analysis revealed a
      gradual conceptual evolution of the model, which includes the notions of family
      centered care, comprehensive care (including bereavement) and early and
      integrative care (also including the antenatal period). A subset of 27 articles
      that made special mention of antenatal aspects showed a similar distribution. In
      this subset, the results of the four descriptive clinical studies showed that, in
      the context of specific programmes, a significant number of couples (between 37
      and 87%) opted for PC and to continue with the pregnancy when the foetus has been
      diagnosed with a lethal illness. CONCLUSIONS: Despite the interest that PC has
      aroused in perinatal medicine, there are no evidence-based empirical studies to
      indicate the best model of care for this clinical setting. The very notion of PC
      has evolved to encompass perinatal PC, which includes, among other things, the
      idea of comprehensive care, and early and integrative care initiated antenatally.

PMID- 22409883
TI  - Risk of allergic reactions to wine, in milk, egg and fish-allergic patients.
AB  - BACKGROUND: European legislators and wine producers still debate on the
      requirement for labeling of wines fined with potentially allergenic food proteins
      (casein, egg white or fish-derived isinglass). We investigated whether wines
      fined with known concentrations of these proteins have the potential to provoke
      clinical allergic reactions in relevant patients. METHODS: In-house wines were
      produced for the study, fined with different concentrations of casein (n = 7),
      egg albumin (n = 1) and isinglass (n = 3). ELISA and PCR kits specific for the
      respective proteins were used to identify the fining agents. Skin prick tests and
      basophil activation tests were performed in patients with confirmed IgE-mediated
      relevant food allergies (n = 24). A wine consumption questionnaire and detailed
      history on possible reactions to wine was obtained in a multinational cohort of
      milk, egg or fish allergic patients (n = 53) and patients allergic to irrelevant
      foods as controls (n = 13). RESULTS: Fining agents were not detectable in wines
      with the available laboratory methods. Nevertheless, positive skin prick test
      reactions and basophil activation to the relevant wines were observed in the
      majority of patients with allergy to milk, egg or fish, correlating with the
      concentration of the fining agent. Among patients consuming wine, reported
      reactions were few and mild and similar with the ones reported from the control
      group. CONCLUSION: Casein, isinglass or egg, remaining in traces in wine after
      fining, present a very low risk for the respective food allergic consumers.
      Physician and patient awareness campaigns may be more suitable than generalized
      labeling to address this issue, as the latter may have negative impact on both
      non-allergic and allergic consumers.

PMID- 22409882
TI  - Identification and characterization of a novel thermostable pyrethroid
      hydrolyzing enzyme isolated through metagenomic approach.
AB  - BACKGROUND: Pyrethroid pesticides are broad-spectrum pest control agents in
      agricultural production. Both agricultural and residential usage is continuing to
      grow, leading to the development of insecticide resistance in the pest and toxic
      effects on a number of nontarget organisms. Thus, it is necessary to hunt
      suitable enzymes including hydrolases for degrading pesticide residues, which is
      an efficient "green" solution to biodegrade polluting chemicals. Although many
      pyrethroid esterases have consistently been purified and characterized from
      various resources including metagenomes and organisms, the thermostable
      pyrethroid esterases have not been reported up to the present. RESULTS: In this
      study, we identified a novel pyrethroid-hydrolyzing enzyme Sys410 belonging to
      familyV esterases/lipases with activity-based functional screening from Turban
      Basin metagenomic library. Sys410 contained 280 amino acids with a predicted
      molecular mass (Mr) of 30.8 kDa and was overexpressed in Escherichia coli BL21
      (DE3) in soluble form. The optimum pH and temperature of the recombinant Sys410
      were 6.5 and 55 degrees C, respectively. The enzyme was stable in the pH range of
      4.5-8.5 and at temperatures below 50 degrees C. The activity of Sys410 decreased
      a little when stored at 4 degrees C for 10 weeks, and the residual activity
      reached 94.1%. Even after incubation at 25 degrees C for 10 weeks, it kept 68.3%
      of its activity. The recombinant Sys410 could hydrolyze a wide range of rho
      nitrophenyl esters, but its best substrate is rho-nitrophenyl acetate with the
      highest activity (772.9 U/mg). The enzyme efficiently degraded cyhalothrin,
      cypermethrin, sumicidin, and deltamethrin under assay conditions of 37 degrees C
      for 15 min, with exceeding 95% hydrolysis rate. CONCLUSION: This is the first
      report to construct metagenomic libraries from Turban Basin to obtain the
      thermostable pyrethroid-hydrolyzing enzyme. The recombinant Sys410 with broad
      substrate specificities and high activity was the most thermostable one of the
      pyrethroid-hydrolyzing esterases studied before, which made it an ideal candidate
      for the detoxification of pyrethroids.

PMID- 22409884
TI  - What factors affect the carriage of epinephrine auto-injectors by teenagers?
AB  - BACKGROUND: Teenagers with allergies are at particular risk of severe and fatal
      reactions, but epinephrine auto-injectors are not always carried as prescribed.
      We investigated barriers to carriage. METHODS: Patients aged 12-18 years old
      under a specialist allergy clinic, who had previously been prescribed an auto
      injector were invited to participate. Semi-structured interviews explored the
      factors that positively or negatively impacted on carriage. RESULTS: Twenty
      teenagers with food or venom allergies were interviewed. Only two patients had
      used their auto-injector in the community, although several had been treated for
      severe reactions in hospital. Most teenagers made complex risk assessments to
      determine whether to carry the auto-injector. Most but not all decisions were
      rational and were at least partially informed by knowledge. Factors affecting
      carriage included location, who else would be present, the attitudes of others
      and physical features of the auto-injector. Teenagers made frequent risk
      assessments when deciding whether to carry their auto-injectors, and generally
      wanted to remain safe. Their decisions were complex, multi-faceted and highly
      individualised. CONCLUSIONS: Rather than aiming for 100% carriage of auto
      injectors, which remains an ambitious ideal, personalised education packages
      should aim to empower teenagers to make and act upon informed risk assessments.

PMID- 22409885
TI  - Methods and metrics challenges of delivery-system research.
AB  - BACKGROUND: Many delivery-system interventions are fundamentally about change in
      social systems (both planned and unplanned). This systems perspective raises a
      number of methodological challenges for studying the effects of delivery-system
      change--particularly for answering questions related to whether the change will
      work under different conditions and how the change is integrated (or not) into
      the operating context of the delivery system. METHODS: The purpose of this paper
      is to describe the methodological and measurement challenges posed by five key
      issues in delivery-system research: (1) modeling intervention context; (2)
      measuring readiness for change; (3) assessing intervention fidelity and
      sustainability; (4) assessing complex, multicomponent interventions; and (5)
      incorporating time in delivery-system models to discuss recommendations for
      addressing these issues. For each issue, we provide recommendations for how
      research may be designed and implemented to overcome these challenges. RESULTS
      AND CONCLUSIONS: We suggest that a more refined understanding of the mechanisms
      underlying delivery-system interventions (treatment theory) and the ways in which
      outcomes for different classes of individuals change over time are fundamental
      starting points for capturing the heterogeneity in samples of individuals exposed
      to delivery-system interventions. To support the research recommendations
      outlined in this paper and to advance understanding of the "why" and "how"
      questions of delivery-system change and their effects, funding agencies should
      consider supporting studies with larger organizational sample sizes; longer
      duration; and nontraditional, mixed-methods designs.A version of this paper was
      prepared under contract with the Agency for Healthcare Research and Quality
      (AHRQ), US Department of Health and Human Services for presentation and
      discussion at a meeting on "The Challenge and Promise of Delivery System
      Research," held in Sterling, VA, on February 16-17, 2011. The opinions in the
      paper are those of the author and do not represent the views or recommendations
      of AHRQ or the US Department of Health and Human Services.1.

PMID- 22409886
TI  - Vaccination against influenza in patients with systemic sclerosis.
AB  - OBJECTIVES: To assess the efficacy and safety of the influenza virus vaccine in
      systemic sclerosis (SSc) patients compared to healthy controls. METHODS: Twenty
      six SSc patients and 16 healthy controls were vaccinated with a trivalent
      influenza subunit vaccine (H1N1 A/Brisbane/59/2007(TGA 2008/81B) (H1N1), H3N2
      A/Uruguay/716/2007 (A/Brisbane/10/2007-like, NIBSC8/124) (H3N2) and B
      B/Brisbane/60/2008 (TGA 2009/82/B) (B)). The subjects were evaluated on the day
      of vaccination and 6 weeks later. Disease activity was assessed by the Rodnan
      score, number of ulcers, number of tender and swollen joints, the presence of
      dyspnea, cough, dyspepsia and dysphagia, and patient (PDAI) and physician (PHDAI)
      disease activity evaluation by the visual activity score (VAS), erythrocyte
      sedimentation rate (ESR) and C-reactive protein (CRP) level. The humoral response
      was evaluated by haemagglutination inhibition (HI). RESULTS: At baseline, 62%,
      15% and 88% of the SSc patients had protective levels against H1N1, H3N2 and B,
      respectively, versus 56%, 62% and 87% for controls. Six weeks later, the
      proportion of responders to H1N1 was significantly higher in the SSc patients
      (73%) compared to controls (37.5%) (p=0.0225). The proportion of responders to
      H3N2 and B was similar in both groups, and both had a significant increase in
      geometric mean titers for each antigen. A lower response to H1N1 was associated
      with interstitial lung disease, while patients on combination calcium channel
      blockers and iloprost therapy showed significantly better response to H1N1 and B
      antigens. Most underlying disease activity parameters remained unchanged.
      CONCLUSIONS: The influenza virus vaccine was safe and generated a satisfactory
      humoral response in SSc patients.

PMID- 22409887
TI  - Clinical outcomes of pyrazinamide-monoresistant Mycobacterium tuberculosis in
      Quebec.
AB  - BACKGROUND: In Quebec, 6.2% of all tuberculosis (TB) isolates from Canadian-born
      patients are resistant to pyrazinamide (PZA) alone. The clinical significance of
      PZA-monoresistant (PZA(MR)) TB is unknown. METHODS: Canadian-born patients with
      PZA(MR) TB diagnosed  between 1 January 1990 and 31 December 2000 and reported in
      a prior study were compared to randomly selected Canadian-born patients with
      fully susceptible isolates diagnosed within the same time period. RESULTS: A
      total of 318 patients were eligible, of whom 40 (12.6%) had missing outcome 
      information. Mean total duration of treatment was respectively 9.0 and 8.9 months
      for those with PZA(MR) and pan-susceptible strains. Respectively 91% and 89% of
      PZA(MR) and pan-susceptible patients received at least 6 months of rifampin
      containing treatment. Among 67 patients  with PZA(MR) TB, 51 (76%) were cured, 3
      (4%) relapsed, none failed treatment, and 16 (24%) died within 6 months of
      diagnosis. Of 211 subjects with fully susceptible isolates, 181 (86%) were cured,
      2 (1%) relapsed, 2 (1%) failed treatment, and 30 (14%) died within 6 months of
      diagnosis.  PZA monoresistance was associated with decreased odds of successful
      clinical outcomes compared with pan-susceptible TB (OR 0.4, 95%CI 0.2-0.8).
      CONCLUSION: Patients with PZA(MR) TB had significantly worse clinical outcomes
      than patients with fully susceptible strains.

PMID- 22409888
TI  - mTOR as a molecular target in HPV-associated oral and cervical squamous
      carcinomas.
AB  - PURPOSE: The incidence of head and neck squamous cell carcinomas (HNSCC)
      associated with human papillomavirus (HPV) infection has increased over the past
      decades in the United States. We aimed at examining the global impact of HPV
      associated HNSCC and whether the established key role of mTOR activation in HNSCC
      is also observed in HPV(+) HNSCC lesions, thereby providing novel treatment
      options for HPV-associated HNSCC patients. EXPERIMENTAL DESIGN: An international
      HNSCC tissue microarray (TMA) was used to analyze the expression of p16(INK4A), a
      surrogate for HPV infection, and Akt-mTOR pathway activation. Results were
      confirmed in a large collection of HPV(-) and HPV(+) HNSCC cases and in a
      cervical cancer (CCSCC) TMA. Observations were validated in HNSCC and CCSCC
      derived cell lines, which were xenografted into immunodeficient mice for
      tumorigenesis assays. RESULTS: Approximately 20% of all HNSCC lesions could be
      classified as HPV(+), irrespective of their country of origin. mTOR pathway
      activation was observed in most HPV(+) HNSCC and CCSCC lesions and cell lines.
      The preclinical efficacy of mTOR inhibition by rapamycin and RAD001 was explored
      in HPV(+) HNSCC and CCSCC tumor xenografts. Both mTOR inhibitors effectively
      decreased mTOR activity in vivo and caused a remarkable decrease in tumor burden.
      These results emphasize the emerging global impact of HPV-related HNSCCs and
      indicate that the activation of the mTOR pathway is a widespread event in both
      HPV(-) and HPV-associated HNSCC and CCSCC lesions. CONCLUSIONS: The emerging
      results may provide a rationale for the clinical evaluation of mTOR inhibitors as
      a molecular targeted approach for the treatment of HPV-associated malignancies.

PMID- 22409890
TI  - [Cancer diagnosis in general practice is like looking for a needle in a
      haystack].

PMID- 22409889
TI  - Allergic diseases in the elderly.
AB  - Demographic distribution of the population is progressively changing with the
      proportion of elderly persons increasing in most societies. This entails that
      there is a need to evaluate the impact of common diseases, such as asthma and
      other allergic conditions, in this age segment. Frailty, comorbidities and
      polymedication are some of the factors that condition management in geriatric
      patients. The objective of this review is to highlight the characteristics of
      allergic diseases in older age groups, from the influence of immunosenescence, to
      particular clinical implications and management issues, such as drug interactions
      or age-related side effects.

PMID- 22409891
TI  - [Uncharacteristic colorectal cancer symptoms and their value in general
      practice].
AB  - Though colorectal cancer is one of the most common cancers in Denmark, there is a
      serious lack of knowledge in general practice about symptom presentation. The
      prevalence and the positive predictive value of the so-called alarm symptoms are
      vague, and screening will only detect a small number of cancers per year. In the
      future, general practice will still play an important role in the diagnosis of
      colorectal cancer; therefore, knowledge about how the disease presents in general
      practice is urgently needed, and intervention studies on how to optimize early
      diagnosis should be encouraged.

PMID- 22409892
TI  - [The genetic background for the eye malformations anophthalmia and
      microphthalmia].
AB  - Anophthalmia and microphthalmia (AO/MO) are rare congenital eye malformations, in
      which the eyeball is apparently absent or smaller than normal, which causes
      various degrees of visual impairment. Over 200 different AO/MO-related syndromes
      have been described, but the genetic background is unknown in many cases. The aim
      of this article is to give an overview of AO/MO, focusing on the genetic
      background. It is illustrated that the future identification of new AO/MO related
      genes will benefit in the genetic counseling of AO/MO patients, and in the
      understanding of eye development and congenital eye malformations.

PMID- 22409893
TI  - [Test of knowledge and skills enhances learning].
AB  - Test-enhanced learning is an evidence-based pedagogical tool for enhancing
      retention of both knowledge and skills. The phenomenon is independent of external
      factors such as feedback and intention to learn. The mechanism is complex and
      possibly related to stress and gender. Tests immediately after learning are most
      effective - and formats that support test-enhanced learning most effectively
      involve composing an answer or actively performing a skill. Use of tests in
      education should be integrated in the curriculum ensuring that the tests
      relevantly complement and enhance learning of knowledge or skills.

PMID- 22409894
TI  - [Sports injuries and arthroscopy--from science to clinical treatment].
AB  - Since the first knee arthroscopy in 1912, it is routine to scope all joints and
      many extra-articular structures. The effect of arthroscopic procedures in overuse
      conditions is sparsely documented and should be investigated in randomized
      studies, but score systems to evaluate clinical effects are lacking. An increased
      understanding of tissue reaction to loading and ligament healing as well as
      neuromuscular control is likely to change the basic principles of treatment and
      prevention in relation to sports injuries.

PMID- 22409895
TI  - [Angio-oedema and medication that interferes with the renin-angiotensin
      aldosterone system--a systematic review].
AB  - Angio-oedema is a rare, but potentially life-threatening side effect to
      medication that interferes with the renin-angiotensin-aldosterone system.
      Clinically controlled trials were reviewed and the incidence assessed. We
      conclude, that treatment with an angiotensin receptor blocker can be tried after
      angiotensin-converting enzyme inhibitor (ACE-I) induced angio-oedema. The
      assessment should be individually based and take the severity of the previous
      attack and the weight of the indication into account. The risk on ACE-I might be
      greater in persons that have had angio-oedema for other reasons.

PMID- 22409896
TI  - [Macrolide resistance in Mycoplasma pneumoniae by recurrence and extended
      illness].
AB  - A 36 year-old female with a Mycoplasma pneumoniae (MP) infection was treated with
      azithromycin. She recovered transitory, but experienced a relapse a few days
      later. After ten days she visited her general practitioner again; she was tired
      and weakened, had a debilitating dry cough and a weight loss of 6 kg. A throat
      swab was positive for MP by a polymerase chain reaction (PCR). It was
      investigated by sequencing and a mutation corresponding to a A2063G transition in
      domain V of the 23S rRNA known to be associated with macrolide resistance was
      detected. Twenty-two days later, MP could still be detected by PCR on a
      nasopharyngeal secretion.

PMID- 22409897
TI  - [Acute compartment syndrome following a total knee arthroplasty].
AB  - Acute compartment syndrome is a rare, but severe complication to knee
      arthroplasty. The main symptoms are extreme pain unrelated to the surgery,
      pulselessness, and tense and pallid skin. The syndrome can be disguised by an
      effective pain management, but due to the consequences, an early diagnosis and
      fasciotomy is important. We describe a case with a patient, who had undergone a
      total knee arthroplasty and after a postoperative period of 5,5 hours she
      developed extreme pain in the limb, below the operated knee. The diagnosis was
      confirmed by sonography, and an acute fasciotomy was performed.

PMID- 22409898
TI  - [Spontaneous bleeding in musculus rectus can be stopped by coil embolisation].
AB  - Spontaneous non-traumatic bleeding could be a fatal condition and the most
      frequent site of bleeding is the rectus sheath or psoas muscle. Successful coil
      embolisation of bleeding epigastric inferior artery and significantly clinical
      improvement in the following days is described.

PMID- 22409899
TI  - [Hip dislocation requires prompt treatment].
AB  - Hip dislocation is an orthopaedic emergency. We report a 79 year-old woman, who
      was brought to the emergency department after falling on her knee at home. An X
      ray confirmed a posterior dislocation of her left hip. A successful prompt
      reduction was performed in the operation room under general anaesthesia. This
      uncommon injury represents an orthopaedic emergency and requires immediate
      reduction to lessen the risk of complications including avascular necrosis of the
      femoral head.

PMID- 22409900
TI  - [Picture of the month: tsutsugamushi disease].

PMID- 22409901
TI  - Subtropical grass pollen allergens are important for allergic respiratory
      diseases in subtropical regions.
AB  - BACKGROUND: Grass pollen allergens are a major cause of allergic respiratory
      disease but traditionally prescribing practice for grass pollen allergen-specific
      immunotherapy has favoured pollen extracts of temperate grasses. Here we aim to
      compare allergy to subtropical and temperate grass pollens in patients with
      allergic rhinitis from a subtropical region of Australia. METHODS: Sensitization
      to pollen extracts of the subtropical Bahia grass (Paspalum notatum), Johnson
      grass (Sorghum halepense) and Bermuda grass (Cynodon dactylon) as well as the
      temperate Ryegrass (Lolium perenne) were measured by skin prick in 233 subjects
      from Brisbane. Grass pollen-specific IgE reactivity was tested by ELISA and cross
      inhibition ELISA. RESULTS: Patients with grass pollen allergy from a subtropical
      region showed higher skin prick diameters with subtropical Bahia grass and
      Bermuda grass pollens than with Johnson grass and Ryegrass pollens. IgE
      reactivity was higher with pollen of Bahia grass than Bermuda grass, Johnson
      grass and Ryegrass. Patients showed asymmetric cross-inhibition of IgE reactivity
      with subtropical grass pollens that was not blocked by temperate grass pollen
      allergens indicating the presence of species-specific IgE binding sites of
      subtropical grass pollen allergens that are not represented in temperate grass
      pollens. CONCLUSIONS: Subtropical grass pollens are more important allergen
      sources than temperate grass pollens for patients from a subtropical region.
      Targeting allergen-specific immunotherapy to subtropical grass pollen allergens
      in patients with allergic rhinitis in subtropical regions could improve treatment
      efficacy thereby reducing the burden of allergic rhinitis and asthma.

PMID- 22409902
TI  - The social gradient in doctor-patient communication.
AB  - OBJECTIVE: In recent years, the importance of social differences in the physician
      patient relationship has frequently been the subject of research. A 2002 review
      synthesised the evidence on this topic. Considering the increasing importance of
      social inequalities in health care, an actualization of this review seemed
      appropriate. METHODS: A systematic search of literature published between 1965
      and 2011 on the social gradient in doctor-patient communication. In this review
      social class was determined by patient's income, education or occupation.
      RESULTS: Twenty original research papers and meta-analyses were included. Social
      differences in doctor-patient communication were described according to the
      following classification: verbal behaviour including instrumental and affective
      behaviour, non-verbal behaviour and patient-centred behaviour. CONCLUSION: This
      review indicates that the literature on the social gradient in doctor-patient
      communication that was published in the last decade, addresses new issues and
      themes. Firstly, most of the found studies emphasize the importance of the
      reciprocity of communication.Secondly, there seems to be a growing interest in
      patient's perception of doctor-patient communication. PRACTICE IMPLICATIONS: By
      increasing the doctors' awareness of the communicative differences and by
      empowering patients to express concerns and preferences, a more effective
      communication could be established.

PMID- 22409903
TI  - Physical growth during the first year of life. A longitudinal study in rural and
      urban areas of Hanoi, Vietnam.
AB  - BACKGROUND: Good infant growth is important for future health. Assessing growth
      is common in pediatric care all over the world, both at the population and
      individual level. There are few studies of birth weight and growth studies
      comparing urban and rural communities in Vietnam. The first aim is to describe
      and compare the birth weight distributions and physical growth (weight and
      length) of children during their first year in one rural and one urban area of
      Hanoi Vietnam. The second aim is to study associations between the anthropometric
      outcomes and indicators of the economic and educational situations. METHODS:
      Totally 1,466 children, born from 1st March, 2009 to June 2010, were followed
      monthly from birth to 12 months of age in two Health and Demographic Surveillance
      Sites; one rural and one urban. In all, 14,199 measurements each of weight and
      length were made. Birth weight was recorded separately. Information about
      demographic conditions, education, occupation and economic conditions of persons
      and households was obtained from household surveys. Fractional Polynomial models
      and standard statistical methods were used for description and analysis. RESULTS:
      Urban infants have higher birth weight and gain weight faster than rural infants.
      The mean birth weight for urban boys and girls were 3,298 grams and 3,203 grams
      as compared to 3,105 grams and 3,057 grams for rural children. At 90 days, the
      urban boys were estimated to be 4.1% heavier than rural boys. This difference
      increased to 7.2% at 360 days. The corresponding difference for girls was 3.4%
      and 10.5%. The differences for length were comparatively smaller. Both birth
      weight and growth were statistically significantly and positively associated with
      economic conditions and mother education. CONCLUSION: Birth weight was lower and
      the growth, weight and length, considerably slower in the rural area, for boys as
      well as for girls. The results support the hypothesis that the rather drastic
      differences in maternal education and economic conditions lead to poor nutrition
      for mothers and children in turn causing inferior birth weight and growth.

PMID- 22409904
TI  - Left ventricular assist device implantation in high risk destination therapy
      patients: an alternative surgical approach.
AB  - Left Ventricular Assist Device (LVAD) for Destination Therapy (DT) is an
      established therapy for end stage heart failure patients who are not transplant
      candidates. Many DT patients requiring LVADs have had prior open heart surgery,
      the majority of whom had prior sternotomy. In addition, DT patients tend to be
      older and more likely to have more significant co-morbidities than their Bridge
      To-Transplant (BTT) counterparts. As such, placement of an implantable LVAD in DT
      patients can be technically hazardous and potentially prone to more perioperative
      complications. The purpose of this report is to describe an alternative
      implantation approach for the implantation of the Heartmate IITM LVAD in high
      risk DT patients.

PMID- 22409905
TI  - Selenium inclusion decreases oxidative stress indicators and muscle injuries in
      sea bass larvae fed high-DHA microdiets.
AB  - The objective of the present study was to determine the effect of Se inclusion in
      high-DHA and vitamin E microdiets (5 g DHA/100 g dry weight and 300 mg vitamin
      E/100 g dry weight; 5 g DHA/100 g dry weight and 300 mg vitamin E/100 g dry
      weight supplemented with Se) in comparison with a control diet (1 g DHA/100 g dry
      weight and 150 mg vitamin E/100 g dry weight) on sea bass larval growth,
      survival, biochemical composition, malonaldehyde (MDA) content, muscle morphology
      and antioxidant enzymes (AOE), insulin-like growth factors (IGF) and myosin
      expression. For a given DHA and vitamin E dietary content, Se inclusion favoured
      larval total length and specific growth rate, and reduced the incidence of
      muscular lesions, MDA contents and AOE gene expression. In contrast, IGF gene
      expression was elevated in the 5/300 larvae, suggesting an increased muscle
      mitogenesis that was corroborated by the increase in mRNA copies of myosin heavy
      chain. The results of the present study denoted the beneficial effect of Se not
      only in preventing oxidative stress, as a glutathione peroxidase cofactor, but
      probably due to other as yet unknown physiological functions.

PMID- 22409906
TI  - Acanthamoeba meningoencephalitis presenting as neuropsychiatric lupus in a
      pediatric patient.
AB  - We present the case of a 16-year-old patient with systemic lupus erythematosus
      who presented with altered mental status and regressive behaviour. She was worked
      up and empirically treated for common and opportunistic infectious agents. All
      work-up was negative and after an extensive course of antibiotics she was treated
      for neuropsychiatric lupus with cytoxan. She initially responded, but this was
      short-lived and she eventually became comatose and passed away. On brain biopsy
      she was found to have numerous trophozoites with round nucleus, prominent
      nucleolus and thin nuclear membrane. Methenamine silver stain showed encysted
      amoeba, corresponding with a diagnosis of acanthamoeba meningoencephalitis.
      Making the diagnosis of acanthamoeba meningoencephalitis requires a high degree
      of suspicion. Specific serum antibodies may not be a reliable measure in
      immunocompromised patients and trophozoites in CSF can be confused with
      monocytes. Brain biopsy may be required to make a definitive diagnosis. It is
      important for clinicians treating immunocompromised patients to keep this agent
      in mind in an immunocompromised patient with neurological manifestations.
      Acanthamoeba infections have only been reported in a small handful of patients
      and, to our knowledge, this is the first reported case in the United States.

PMID- 22409907
TI  - Comparing the effects of two inhaled glucocorticoids on allergen-induced
      bronchoconstriction and markers of systemic effects, a randomised cross-over
      double-blind study.
AB  - BACKGROUND: Inhaled glucocorticoids are efficient in protecting against asthma
      exacerbations, but methods to compare their efficacy vs systemic effects have
      only been attempted in larger multi-centre studies. The aim of the current study
      was therefore to directly compare the effects of two separate inhaled
      glucocorticoids, mometasone and budesonide, to compare the effects on the early
      and late asthmatic responses to inhaled allergen in patients with mild allergic
      asthma, and sputum eosinophils, and to relate the clinical positive effects to
      any systemic effects observed. METHODS: Twelve patients with documented early and
      late asthmatic responses (EAR and LAR) to inhaled allergen at a screening visit
      were randomized in a double-blind fashion to treatment with mometasone (200 MUg *
      2 or 400 MUg * 2), budesonide (400 MUg * 2) or placebo in a double-blind
      crossover fashion for a period of seven days. Challenge with the total allergen
      dose causing both an EAR and LAR was given on the last day of treatment taken in
      the morning. Lung function was assessed using FEV1, and systemic glucocorticoid
      activity was quantified using 24 h urinary cortisol. RESULTS: Mometasone and
      budesonide attenuate both EAR and LAR to allergen to a similar degree. No
      significant dose-related effects on the lung function parameters were observed.
      Both treatments reduced the relative amount of sputum eosinophils (%) after
      allergen. At the dose of 800 MUg daily, mometasone reduced 24 h urinary cortisol
      by approximately 35%. Both drugs were well tolerated. CONCLUSIONS: Mometasone and
      budesonide are equieffective in reducing early and late asthmatic responses
      induced by inhaled allergen challenge. Mometasone 800 MUg given for seven days
      partially affects the HPA axis.

PMID- 22409908
TI  - FAST: towards safe and effective subcutaneous immunotherapy of persistent life
      threatening food allergies.
AB  - The FAST project (Food Allergy Specific Immunotherapy) aims at the development of
      safe and effective treatment of food allergies, targeting prevalent, persistent
      and severe allergy to fish and peach. Classical allergen-specific immunotherapy
      (SIT), using subcutaneous injections with aqueous food extracts may be effective
      but has proven to be accompanied by too many anaphylactic side-effects. FAST aims
      to develop a safe alternative by replacing food extracts with hypoallergenic
      recombinant major allergens as the active ingredients of SIT. Both severe fish
      and peach allergy are caused by a single major allergen, parvalbumin (Cyp c 1)
      and lipid transfer protein (Pru p 3), respectively. Two approaches are being
      evaluated for achieving hypoallergenicity, i.e. site-directed mutagenesis and
      chemical modification. The most promising hypoallergens will be produced under
      GMP conditions. After pre-clinical testing (toxicology testing and efficacy in
      mouse models), SCIT with alum-absorbed hypoallergens will be evaluated in phase
      I/IIa and IIb randomized double-blind placebo-controlled (DBPC) clinical trials,
      with the DBPC food challenge as primary read-out. To understand the underlying
      immune mechanisms in depth serological and cellular immune analyses will be
      performed, allowing identification of novel biomarkers for monitoring treatment
      efficacy. FAST aims at improving the quality of life of food allergic patients by
      providing a safe and effective treatment that will significantly lower their
      threshold for fish or peach intake, thereby decreasing their anxiety and
      dependence on rescue medication. 

PMID- 22409909
TI  - Cortico-cerebellar functional connectivity and sequencing of movements in
      schizophrenia.
AB  - BACKGROUND: Abnormal execution of several movements in a sequence is a frequent
      finding in schizophrenia. Successful performance of such motor acts requires
      correct integration of cortico-subcortical processes, particularly those related
      to cerebellar functions. Abnormal connectivity between cortical and cerebellar
      regions with resulting cognitive dysmetria has been proposed as the core
      dysfunction behind many signs and symptoms of schizophrenia. The aim of the
      present study was to assess if these proposed abnormalities in connectivity are a
      unifying feature of schizophrenia, or, rather, reflect a specific symptom domain
      of a heterogeneous disease. We predicted that abnormal functional connectivity
      between the motor cortex and cerebellum would be linked with abnormal performance
      of movement sequencing. METHODS: We examined 24 schizophrenia patients (SCH) and
      24 age-, sex-, and handedness-matched healthy controls (HC) using fMRI during a
      modified finger-tapping task. The ability to perform movement sequencing was
      tested using the Neurological Evaluation Scale (NES). The subjects were
      categorized into two groups, with (SQ+) and without (SQ-) movement sequencing
      abnormalities, according to the NES-SQ score. The effects of diagnosis and
      movement sequencing abnormalities on the functional connectivity parameters
      between the motor cortex and cerebellum (MC-CRBL) and the supplementary motor
      cortex and cerebellum (SMA-CRBL) activated during the motor task were analyzed.
      RESULTS: We found no effect of diagnosis on the functional connectivity measures.
      There was, however, a significant effect on the SQ group: SQ + patients showed a
      lower level of MC-CRBL connectivity than SQ- patients and healthy controls.
      Moreover, the level of MC-CRBL and SMA-CRBL negatively correlated with the
      magnitude of NES-SQ abnormalities, but with no other NES domain. CONCLUSIONS:
      Abnormal cortico-cerebellar functional connectivity during the execution of a
      motor task is linked with movement sequencing abnormalities in schizophrenia, but
      not with the diagnosis of schizophrenia per se. It seems that specific patterns
      of inter-regional connectivity are linked with corresponding signs and symptoms
      of clinically heterogeneous conditions such as schizophrenia.

PMID- 22409910
TI  - Metabolomic profiles of myocardial ischemia under treatment with salvianolic acid
      B.
AB  - BACKGROUND: Radix Salvia miltiorrhiza (Danshen) has been used as a principal herb
      in treating cardiovascular diseases in Chinese medicine. Salvianolic acid B (SA
      B), a water-soluble active component of Danshen, was found to have anti
      myocardial ischemia (anti-MI) effect. This study aims to investigate mechanisms
      of SA-B on MI. METHODS: Five conventional Western medicines (isosorbide
      dinitrate, verapamil, propranolol, captopril and trimethazine) with different
      mechanisms for treating cardiovascular diseases were selected as positive
      references to compare with SA-B in changing of the metabolomic profiles in MI
      rats under treatment. Potential mechanisms of SA-B were further investigated in
      H9C2 cell line. RESULTS: The metabolomic profiles between SA-B- and propranolol
      treated MI rats were similar, since there was a big overlap between the two
      groups in the PLS-DA score plot. Finally, it was demonstrated that SA-B exhibited
      a protective effect on MI mainly by decreasing the concentration of cyclic
      adenosine monophosphate (cAMP) and Ca2+ and inhibiting protein kinase A (PKA).
      CONCLUSION: SA-B and propanolol exhibited similar metabolomic profiles,
      indicating that the two drugs might have a similar mechanism.

PMID- 22409911
TI  - Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced
      insulin resistance in L6 skeletal muscle cells.
AB  - BACKGROUND: Fatty acid-induced insulin resistance and impaired glucose uptake
      activity in muscle cells are fundamental events in the development of type 2
      diabetes and hyperglycemia. There is an increasing demand for compounds including
      drugs and functional foods that can prevent myocellular insulin resistance.
      METHODS: In this study, we established a high-throughput assay to screen for
      compounds that can improve myocellular insulin resistance, which was based on a
      previously reported non-radioisotope 2-deoxyglucose (2DG) uptake assay. Insulin
      resistant muscle cells were prepared by treating rat L6 skeletal muscle cells
      with 750 MUM palmitic acid for 14 h. Using the established assay, the impacts of
      several fatty acids on myocellular insulin resistance were determined. RESULTS:
      In normal L6 cells, treatment with saturated palmitic or stearic acid alone
      decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co
      treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG
      uptake activity. Using the developed assay with palmitic acid-induced insulin
      resistant L6 cells, we determined the effects of other unsaturated fatty acids.
      We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved
      palmitic acid-decreased 2DG uptake at lower concentrations than the other
      unsaturated fatty acids, including oleic acid, as 10 MUM arachidonic acid showed
      similar effects to 750 MUM oleic acid. CONCLUSIONS: We have found that
      polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids
      prevent palmitic acid-induced myocellular insulin resistance.

PMID- 22409912
TI  - A Westerner's question about traditional Chinese medicine: are the Yinyang
      concept and the Wuxing concept of equal philosophical and medical rank?
AB  - There is no question that the theoretical and practical value of the Yinyang
      concept is by far higher than the value of the Wuxing concept. I consider Yin and
      Yang as one of the greatest discoveries ever made, being deep philosophy as well
      as deep science. Using this concept seems usefull even in combination with the
      most advanced methods of modern pathology, diagnosis and therapy. The Wuxing
      concept, however, I consider as a purely speculative system without logic and
      reason. The probability that it leads to useless or even wrong conclusion seems
      much higher than the possibility to result in something usefull. I know tha many
      TCM authors and practitioners will object. However, I see good reasons to demand
      one thing: that they should prove in detail, why they consider that Wuxing
      concept not only as helpful and useful, but even as essential for the future of
      TCM.

PMID- 22409913
TI  - An updated review on the parasitic herb of Cuscuta reflexa Roxb.
AB  - Cuscuta reflexa Roxb. is a golden yellow, leafless, perennial, parasitic herb of
      the family Convolvulaceae. C. reflexa has been investigated for antispasmodic,
      hemodynamic, anticonvulsant, anti steroidogenic, antihypertensive, muscle
      relaxant, cardiotonic, antiviral, antibacterial, antioxidant, cholinergic,
      diuretic and hair growth activities. Many chemical constituents have been
      isolated from C. reflexa such as cuscutin, amarbelin, beta-sitosterol,
      stigmasterol, kaempferol, dulcitol, myricetin, quercetin, coumarin and oleanolic
      acid. This review presents a detailed survey of the literature on pharmacognosy,
      phytochemistry and traditional and biological medicinal uses of C. reflexa.

PMID- 22409914
TI  - Advances in Smoothened-targeting therapies for pancreatic cancer: implication for
      drug discovery from herbal medicines.
AB  - Smoothened (SMO) is a member of sonic hedgehog homology (SHH) signaling pathway.
      It plays a key role as a bridge between patched-1 (PTCH-1) and Gli. Aberrant SHH
      expression can be detected in various malignant tissues, and the expression in
      pancreatic cancer stem cells is higher apparently. SHH signals are closely
      associated with self-duplication of cancer stem cells, formation of tumor vessels
      as well as matrixes. SMO antagonists such as cyclopamine, GDC-0449 and so on show
      potential to inhibit activity of SHH signaling, and arrest the growth as well as
      metastases of tumors. Recently, a few of SMO antagonists have been studied in
      phase I clinical trials and some are in phase II, meanwhile, phase I or II trials
      of SMO antagonists to treat pancreatic cancer are performed currently. As the
      classical SMO antagonist, cyclopamine is extracted from a medicinal plant.
      Perhaps researchers may be able to determine more effective SMO-targeting drugs
      from herbal medicines in the future.

PMID- 22409915
TI  - [Application of Delphi method in traditional Chinese medicine clinical research].
AB  - In recent years, Delphi method has been widely applied in traditional Chinese
      medicine (TCM) clinical research. This article analyzed the present application
      situation of Delphi method in TCM clinical research, and discussed some problems
      presented in the choice of evaluation method, classification of observation
      indexes and selection of survey items. On the basis of present application of
      Delphi method, the author analyzed the method on questionnaire making, selection
      of experts, evaluation of observation indexes and selection of survey items.
      Furthermore, the author summarized the steps of application of Delphi method in
      TCM clinical research.

PMID- 22409916
TI  - [Modern testing theory and its application in the field of health measurement].
AB  - This paper briefly introduces item response theory (IRT) as a typical
      representation of modern testing theory (MTT), and systematically reviews the
      processes and contents of the application of IRT in the area of health
      measurement, including, for example, item bank development, scale revision and
      computerized adaptive testing. The author presents the potential benefits and the
      notable problems during health measuring by IRT. Then, the author asserts the
      need for thorough assessment of feasibility when using the IRT in patient
      reported outcome research. Further research based on IRT and computerized
      adaptive testing in health measurement will be carried out in the field of
      medical care including traditional Chinese medicine and integrative medicine.

PMID- 22409917
TI  - [Systematic review on methodology of randomized controlled trials of post
      marketing Chinese patent drugs for treatment of type 2 diabetes].
AB  - BACKGROUND: Randomized controlled trial (RCT) is considered as the gold standard
      for the efficacy assessment of medicines. With the increasing number of Chinese
      patent drugs for treatment of type 2 diabetes, the methodology of post-marketing
      RCTs evaluating the efficacy and specific effect has become more important.
      OBJECTIVE: To investigate post-marketing Chinese patent drugs for treatment of
      type 2 diabetes, as well as the methodological quality of post-marketing RCTs.
      SEARCH STRATEGY: Literature was searched from the books of Newly Compiled
      Traditional Chinese Patent Medicine and Chinese Pharmacopeia, the websites of the
      State Food and Drug Administration and the Ministry of Human Resources and Social
      Security of the People's Republic of China, China National Knowledge
      Infrastructure Database, Chongqing VIP Chinese Science and Technology Periodical
      Database, Chinese Biomedical Database (SinoMed) and Wanfang Data. The time period
      for searching ran from the commencement of each database to August 2011.
      INCLUSION CRITERIA: RCTs of post-marketing Chinese patent drugs for treatment of
      type 2 diabetes with intervention course no less than 3 months. DATA EXTRACTION
      AND ANALYSIS: Two authors independently evaluated the research quality of the
      RCTs by the checklist of risk bias assessment and the data collection forms based
      on the CONSORT Statement. Independent double data-extraction was performed.
      RESULTS: The authors identified a total of 149 Chinese patent drugs for treatment
      of type 2 diabetes. According to different indicative syndromes, the Chinese
      patent drugs can be divided into the following types, namely, yin deficiency and
      interior heat (n=48, 32%), dual deficiency of qi and yin (n=58, 39%) and dual
      deficiency of qi and yin combined with blood stasis (n=22, 15%). A total of 41
      RCTs meeting the inclusion criteria were included. Neither multicenter RCTs nor
      endpoint outcome reports were found. Risk bias analysis showed that 81% of the
      included studies reported randomization for grouping without sequence generation,
      98% of these studies did not report concealment of random numbers, 5% used
      placebo, 10% reported outcome attrition bias and no study employed the analysis
      of intention-to-treat and 98% reported the diagnostic criteria for type 2
      diabetes. The participants mainly consisted of outpatients without complications
      (76%). The minimum and maximum sample size was 40 and 300 (106 +/- 60),
      respectively. CONCLUSION: The inclusion and exclusion criteria and outcome
      measures did not match the purposes and contents of post-marketing research in
      the included studies. They also failed to reflect the basic principles of
      traditional Chinese medicine in the process of diagnosis and treatment. The
      demographic characteristics of the patients, the indications for medicine and the
      syndrome differentiation process were not reported sufficiently and
      transparently. In order to improve the post-marketing research and promote the
      rational use of Chinese patent drugs, it is recommended that phase IV clinical
      trials should establish clear research purpose as well as hypothesis first, and
      choose scientific and evidence-based study design and outcome measures. In
      addition, guidelines for implementation of post-marketing research should be
      developed.

PMID- 22409918
TI  - Study strategies for acupuncture treatment of chronic nonbacterial prostatitis.
AB  - By retrospectively reviewing the current status of traditional Chinese medicine
      (TCM) and Western medicine treatments of chronic nonbacterial prostatitis (CNP),
      the TCM understanding of its etiologies and pathogenesis, the therapeutic
      principles and the mechanisms of acupuncture treatment of CNP, the clinical study
      strategies of acupuncture treatment for CNP were further proposed, which could
      provide more scientific basis and support for the definite longer-term
      therapeutic efficacy of acupuncture treatment of CNP. Breakthrough in the
      treatment of CNP will be achieved with the application of acupuncture therapy
      both in clinical practice and experimental research.

PMID- 22409919
TI  - Estimation of sample size and testing power (part 6).
AB  - The design of one factor with k levels (k >= 3) refers to the research that only
      involves one experimental factor with k levels (k >= 3), and there is no
      arrangement for other important non-experimental factors. This paper introduces
      the estimation of sample size and testing power for quantitative data and
      qualitative data having a binary response variable with the design of one factor
      with k levels (k >= 3).

PMID- 22409920
TI  - Evaluation of the immediate effects of manual acupuncture on brachial bicep
      muscle function in healthy individuals and post stroke patients: a study protocol
      of a parallel-group randomized clinical trial.
AB  - BACKGROUND: Stroke is a morbid entity in Chinese medicine recognized for over 2
      000 years with sensory-motor impairments reported by several classical authors.
      However, the majority of controlled clinical trials of acupuncture in the
      treatment of post stroke recovery failed to obtain significant long-term results
      on functional recovery. Moreover, contradictory results have been obtained
      regarding the immediate effects of acupuncture stimulation on the electrical
      activity of human skeletal muscles as observed using surface electromyography.
      These results raise the question of whether acupuncture has any effect on the
      neuromuscular level. This study aims to evaluate the immediate effects of manual
      acupoint stimulation on the electrical activity and strength of the biceps
      brachii of healthy individuals and patients with chronic hypertonic hemiparesis.
      METHODS AND DESIGN: The study proposes a single-blinded randomized clinical trial
      with four parallel groups. Healthy subjects and post stroke patients with chronic
      spastic hemiparesis will be submitted to a single acupuncture intervention
      puncturing either Quchi (LI11) or Tianquan (PC2). The immediate effects on muscle
      function will be assessed by surface electromyography and isometric force of the
      biceps brachii muscle as the primary outcome. Secondary outcomes comprise the
      frequency of patterns in each group, as well as the frequency distribution of
      manifestations. DISCUSSION: The proposed study design includes some improvements
      on common methodological issues on clinical trials with an integrative design.
      This study design is expected to provide new insights on the neuromuscular
      effects of acupuncture stimulation in healthy subjects and post stroke patients.
      TRIAL REGISTRATION: Brazilian Clinical Trials Registry
      (www.ensaiosclinicos.gov.br) in English and Portuguese in October 2011.
      REGISTRATION NUMBER: RBR-5g7xqh.

PMID- 22409921
TI  - [Effects of Chinese herbal medicine Bushen Huoxue Granule on quality of life of
      patients with Parkinson disease: a randomized, double-blinded and placebo
      controlled trial].
AB  - BACKGROUND: The main clinical symptoms of Parkinson disease (PD) are resting
      tremor, muscle rigidity and bradykinesia. There is currently no effective
      treatment for PD, and dyskinesia symptoms affect the quality of life of patients
      with PD. The Chinese medicine therapy used for reinforcing kidney and activating
      blood circulation in treatment of PD was reported to achieve good clinical
      effects. OBJECTIVE: To study the effects of Bushen Huoxue Granule, a compound
      traditional Chinese herbal medicine, on the quality of life of patients with PD.
      DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 120 patients were
      enrolled from General Hospital of the People's Liberation Army in China and
      divided into two groups randomly. Patients in the control group were treated with
      a placebo and in the treatment group with Bushen Huoxue Granule based on treating
      with levodopa. A double-blinded clinical trial was adopted over a 3-month
      treatment with a follow-up period lasting 6 months. MAIN OUTCOME MEASURES:
      Unified Parkinson Disease Rating Scale II (UPDRS II), questionnaire-39 (PDQ-39)
      and Parkinson's disease sleep scale (PDSS) were adopted to measure the quality of
      life at baseline, after 3 months of treatment and at a 6-month follow-up.
      RESULTS: Bushen Huoxue Granule showed a higher efficacy than the control in
      improving life quality of patients with PD by improving scores of UPDRS II, PDQ
      39 and PDSS (P<0.05). No adverse effects were found in this trial. CONCLUSION:
      Bushen Huoxue Granule can markedly improve the quality of life of patients with
      PD.

PMID- 22409922
TI  - [Effects of the Chinese patent medicine, Honghua Injection, on platelet
      glycoprotein IIb/III a receptors in patients with acute coronary syndrome: a
      randomized controlled trial].
AB  - BACKGROUND: Glycoprotein (GP) IIb/IIIa is an important index for assessing the
      function of platelets. To investigate the effects of Honghua Injection, a Chinese
      patent medicine made from extracts of Carthamus tinctorius L, on GP IIb/IIIa is a
      key study in evaluating the inhibition properties of Honghua Injection on
      platelet aggregation. OBJECTIVE: To observe the effects of Honghua Injection on
      platelet GPIIb/IIIa receptors and explore the mechanisms of Honghua Injection in
      inhibiting platelet aggregation in patients with acute coronary syndrome. DESIGN,
      SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 64 patients from Yueyang
      Hospital of Traditional Chinese and Western Medicine affiliated to Shanghai
      University of Traditional Chinese Medicine were randomly divided into Honghua
      Injection group (n=32, routine Western medicine plus Honghua Injection) and
      control group (n=32, routine Western medicine) according to the random number
      table. The patients were treated for 14 d. MAIN OUTCOME MEASURES: The expressions
      of GPIIb/IIIa (CD41), P-selection (CD62p), and lysosome-associated membrane GP
      (CD63) were measured by flow cytometry before and after treatment. Meanwhile the
      therapeutic effects of Huonghua Injection on angina and short-term prognosis were
      observed. RESULTS: The observational period was 14 d and four patients in the
      control group were omitted due to early discharge. The expression of CD41 in both
      the Honghua Injection group and the control group was inhibited after treatment
      (P<0.05, P<0.01). The inhibition of the Honghua Injection group was stronger than
      that of the control group (P<0.05). There was no case of death, myocardial
      infarction and cerebral apoplexy during 14 d of treatment. The improvement of
      angina symptoms and electrocardiographic manifestation in the Honghua Injection
      group was greater than that of the control group (P<0.05). CONCLUSION: Honghua
      Injection can inhibit the expression of GP IIb/IIIa receptors by preventing
      aggregation of platelets and may be considered as an effective traditional
      Chinese medicine for acute coronary syndrome.

PMID- 22409923
TI  - [Effects of added therapy with Chinese herbal medicine Kanli Granule on skeletal
      muscle dysfunction in patients with chronic heart failure].
AB  - BACKGROUND: The pathological changes of skeletal muscle dysfunction in chronic
      heart failure (CHF) have caused widespread concern, and evaluating the functional
      properties of medication to improve these pathological changes has become a
      common area of study for clinicians. OBJECTIVE: To investigate the
      characteristics of skeletal muscle dysfunction in patients with CHF and the
      effects of Kanli Granule, a compound traditional Chinese herbal medicine, on the
      skeletal muscle dysfunction based on Western medical treatment in patients with
      CHF. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: All patients with CHF
      enrolled in this study were outpatients or inpatients in Shuguang Hospital
      affiliated to Shanghai University of Traditional Chinese Medicine from December
      2005 to December 2007. The patients were divided into Western medicine group
      (treatment with Western medicine) and Chinese herbs group (treatment with Kanli
      Granule based on Western medicine) based on their preference. The treatment
      course lasted for 12 weeks. MAIN OUTCOME MEASURES: The grip strength, grasp
      times, rate of perceived exertion (RPE), estimated heart rate, peripheral blood
      lactate levels and lactate dehydrogenase (LDH) isoenzyme activity in patients
      were measured. RESULTS: A total of 92 patients were recruited and 12 patients
      withdrew from the Western medicine group, therefore a total of 80 patients were
      included in the follow-up study. There were 46 cases in the Chinese herbs group
      and 34 cases in the Western medicine group. After treatment, grip strength and
      grasp times increased significantly compared with before treatment. RPE score and
      estimated heart rate significantly decreased in the two groups, showing greater
      changes in the Chinese herbs group than the Western medicine group (P<0.01).
      Peripheral blood lactate levels of the CHF patients in a resting state decreased,
      and the Chinese herbs group displayed a greater decrease than the Western
      medicine group (P<0.05); lactate levels 3 min after exercise decreased after
      treatment in both treatment groups, but no significant difference was found
      compared with before treatment; LDH1 levels in the two treatment groups were
      decreased compared with before treatment but showed no statistically significant
      changes; LDH5 levels in the two treatment groups increased after treatment, and
      an obvious difference was found in the Chinese herbs group (P<0.01). CONCLUSION:
      Treatment with the addition of Kanli Granule can significantly improve the
      function of skeletal muscle in patients with CHF by improving skeletal muscle
      energy metabolism.

PMID- 22409924
TI  - [Effects of a compound Chinese medicine Xinji' erkang on isoproterenol-induced
      ventricular remodeling in mice].
AB  - OBJECTIVE: To investigate the effects of Xinji' erkang (XJEK), a compound Chinese
      herbal medicine, on isoproterenol-induced ventricular remodeling in mice.
      METHODS: Isoproterenol was given subcutaneously (1 mg/kg, twice per day for 7 d)
      to induce ventricular remodeling in mice. Mice were divided into normal control
      group, model group, XJEK low-, medium- and high- dose groups, XJEK water layer
      group, XJEK n-butanol layer group and metoprolol group. All drugs were given by
      intragastric administration. At the end of the 7th day, the hearts of the rats
      were weighted, and myocardial hypertrophy index was expressed as heart
      weight/body weight (HW/BW). The histological changes were observed by hemotoxylin
      eosin and Van Gieson staining. Colorimetric method was used to determine the
      content of hydroxyproline in heart, and the activity of superoxide dismutase
      (SOD) and the content of malondialdehyde (MDA) in serum. RESULTS: Compared with
      the isoproterenol injection only, XJEK potently inhibited cardiomyocyte
      hypertrophy and the increase of hydroxyproline content in heart (P<0.01),
      improved cardiac pathology change, inhibited the decrease of SOD activity and the
      increase of MDA content in serum (P<0.01). XJEK water layer also inhibited the
      increase of cardiomyocyte hypertrophy (P<0.01) while XJEK n-butanol layer
      inhibited cardiomyocyte hypertrophy and fibrosis (P<0.01). CONCLUSION: XJEK
      possesses protective effects against isoproterenol-induced ventricular remodeling
      in mice, which may be related to its actions in reducing the oxidative stress and
      improving the antioxidant activity of the body. XJEK water layer and XJEK n
      butanol layer attenuated ventricular remodeling without significant oxidative
      stress state changing, which indicates that a non-antioxidative stress mechanism
      may exist.

PMID- 22409925
TI  - Potential of the homeopathic remedy, Arnica Montana 30C, to reduce DNA damage in
      Escherichia coli exposed to ultraviolet irradiation through up-regulation of
      nucleotide excision repair genes.
AB  - OBJECTIVE: To examine to what degree an ultra-highly diluted homeopathic remedy,
      Arnica Montana 30C (AM-30C), used in the treatment of shock and injury, can
      modulate the expression of nucleotide excision repair genes in Escherichia coli
      exposed to ultraviolet (UV) irradiation. METHODS: E. coli were cultured to their
      log phase in a standard Luria-Bertani medium and then exposed to sublethal doses
      of UV irradiation at 25 and 50 J/m(2) for 22.5 and 45 s, respectively. The UV
      exposed bacteria were then supplemented with either AM-30C (drug) or placebo (P
      30C). The drug-treated and placebo-treated bacteria were subjected to assay for
      DNA damage and oxidative stress 90 min after UV exposure. Several protocols like
      comet assay, gel electrophoresis for DNA ladder and intracellular reactive oxygen
      species (ROS) generation, and biomarker measurement like superoxide dismutase
      (SOD), catalase (CAT) and reduced glutathione (GSH) were conducted. The mRNA
      expressions of the excision repair genes like ultraviolet repair uvrA, B and C
      genes (or also known as excision repair genes) were estimated by reverse
      transcription-polymerase chain reaction method. RESULTS: The UV-exposed bacteria
      showed DNA damage and oxidative stress, as revealed by an increase in ROS
      generation, and a decrease in SOD, CAT and GSH activities. As compared to
      placebo, the AM-30C-treated bacteria showed less DNA damage and oxidative stress
      as manifested by a decrease in ROS generation, and an increase in SOD, CAT and
      GSH activities. AM-30C also up-regulated the expression of repair genes as
      compared to the control. CONCLUSION: AM-30C helped repair the DNA damage through
      up-regulation of repair genes and also ameliorated the oxidative stress through
      the reduction of ROS generation and suitable modulation of anti-oxidative stress
      enzymes.

PMID- 22409926
TI  - Evaluation of the antidiarrheal activity of the plant extracts of Ficus species.
AB  - OBJECTIVE: The Khandesh region of Jalgaon district, India has a dense forest with
      plenty of medicinal plants which have been used as folklore medicines by the
      local people for many years. They use different parts of Ficus species to treat
      and cure diarrhea. Depending on the traditional use of some plants as
      antidiarrheal by local people of that region, the authors have selected three
      plants (specific parts) to evaluate their antidiarrheal activities in different
      animal models. METHODS: Wistar albino rats weighing 180 to 200 g of either sex
      were used in this study. There were eight groups for each individual study with
      10 animals in each group. The antidiarrheal profile of the ethanolic extracts of
      the bark of Ficus bengalensis and the leaves of Ficus racemosa and Ficus carica
      from the region of Khandesh in Jalgaon district of Maharashtra, India were
      evaluated by different experimental models, namely, castor oil-induced diarrhea,
      gastrointestinal motility test, prostaglandin E2 (PGE2)-induced enteropooling in
      Wistar albino rats. RESULTS: The extracts of F. bengalensis (bark), F. racemosa
      (leaves) and F. carica (leaves) showed significant inhibitory activities against
      castor oil-induced diarrhea and PGE2-induced enteropooling in rats. The ethanolic
      extracts at 400 and 600 mg/kg significantly inhibited diarrhea. There was a
      significant dose-dependent decrease in diarrhea produced by all the three models
      in rats as compared to that of the standard drug group (P<0.01). Based on the
      results in experimental rat models, the ethanolic extract of Ficus species
      demonstrated significant reductions in faecal output and frequency of droppings
      when compared to the castor oil-treated rats (P<0.01). All plant extracts also
      significantly retarded the propulsion of charcoal meal and significantly
      inhibited PGE(2)-induced enteropooling. CONCLUSION: All these plant materials can
      be claimed as potential antidiarrheal agents. The underlying mechanism appears to
      be spasmolytic and an anti-enteropooling property by which the different plant
      extracts produced relief in diarrhea. Tannins and flavonoids present in the plant
      extracts may be responsible for the antidiarrheal activity.

PMID- 22409927
TI  - Comparative study on WHO Western Pacific Region and World Federation of Chinese
      Medicine Societies international standard terminologies on traditional medicine:
      triple energizer pattern identification/syndromes differentiation.

PMID- 22409928
TI  - NAT2 polymorphisms and susceptibility to anti-tuberculosis drug-induced liver
      injury: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Although a series of studies have evaluated the
      potential association between N-acetyltransferase 2 (NAT2) polymorphisms and the
      risk of anti-tuberculosis drug-induced liver injury (ATLI), the results have
      generally been controversial and inadequate,  mainly due to limited power. The
      present meta-analysis sought to resolve this problem. DESIGN: PubMed, Embase and
      Web of Science were searched using the following key words: 'N-acetyltransferase
      2' or 'NAT2' and 'polymorphism' and 'tuberculosis'  or 'TB' and 'hepatotoxicity'
      or 'liver injury'. Crude odds ratios (ORs) with 95% confidence intervals (CIs)
      were summarised in forest plots and set out in a table. RESULTS: A total of 14
      studies, comprising 474 cases and 1446 controls, were included in  the meta
      analysis. A significant association was observed between NAT2 slow acetylators
      and the risk of ATLI. The OR for NAT2 slow acetylators compared with rapid
      acetylators was 4.697 (95%CI 3.291-6.705, P < 0.001). Subgroup analyses indicate
      that both Asian  and non-Asian cases with slow acetylators develop ATLI more
      frequently, which is similar to patients with slow acetylators receiving first
      line combination treatment. On comparing NAT2 intermediate acetylators with rapid
      acetylators, the OR for ATLI was 1.261 (95%CI 0.928-1.712,  P = 0.138).
      CONCLUSIONS: This meta-analysis showed that tuberculosis patients with slow
      acetylators had a higher risk of ATLI than other acetylators. Screening of
      patients for the NAT2 genetic polymorphisms will be useful for the clinical
      prediction and prevention of ATLI.

PMID- 22409929
TI  - Current and emerging concepts on the role of peripheral signals in the control of
      food intake and development of obesity.
AB  - The gastrointestinal peptides are classically known as short-term signals,
      primarily inducing satiation and/or satiety. However, accumulating evidence has
      broadened this view, and their role in long-term energy homeostasis and the
      development of obesity has been increasingly recognised. In the present review,
      the recent research involving the role of satiation signals, especially ghrelin,
      cholecystokinin, glucagon-like peptide 1 and peptide YY, in the development and
      treatment of obesity will be discussed. Their activity, interactions and release
      profile vary constantly with changes in dietary and energy influences, intestinal
      luminal environment, body weight and metabolic status. Manipulation of gut
      peptides and nutrient sensors in the oral and postoral compartments through diet
      and/or changes in gut microflora or using multi-hormone 'cocktail' therapy are
      among promising approaches aimed at reducing excess food consumption and body
      weight gain.

PMID- 22409930
TI  - Prognostic role of coronary calcification in patients with rheumatoid arthritis
      and systemic lupus erythematosus.
AB  - OBJECTIVES: To study the predictive value of coronary calcification score (CCS)
      for future cardiovascular (CVS) events as detected by multi-detector computed
      tomography (MDCT) in patients with rheumatoid arthritis(RA) and systemic lupus
      erythematosus (SLE). METHODS: A total of 152 patients with RA and SLE, and 106
      healthy controls underwent MDCT to measure CCS. All patients were prospectively
      followed up for major CVS events. RESULTS: Compared with controls, patients with
      RA and SLE had a significantly higher mean CCS (42.2+/-154.3 vs. 1.4+/-13.0,
      p<0.01) and prevalence of CCS 1-10, CCS 11-100 and CCS>100 (all p<0.05). After a
      mean period of 4.3+/-0.6 years, major CVS events occurred in 10 patients with RA
      and SLE. In patients with RA and SLE, a higher major CVS events rate occurred in
      patients with CCS 1-10 (5.0%), CCS 11-100 (14.3%) and CCS >100 (40.0%) than those
      with CCS=0 (1.0%, p<0.01). Multivariate Cox regression analysis revealed that
      hypercholesterolemia (hazard ratio (HR) 11.2, confidence interval (CI 1.4-89.3,
      p=0.02) and CCS>100 (HR 11.1, CI 1.31-95.0, p=0.03) were independent predictors
      of combined events. CONCLUSIONS: Coronary calcification detected by MDCT
      independently predicts CVS events in patients with RA and SLE. Risk
      stratification by assessment of CCS may have an important role in patients with
      systemic inflammatory disease.

PMID- 22409931
TI  - Stimulating growth and xylindein production of Chlorociboria aeruginascens in
      agar-based systems.
AB  - Four isolates of Chlorociboria aeruginascens were tested for possible
      stimulatory effects when grown on malt agar media containing wood additives. The
      addition of any of the four types of test wood (Acer saccharum, Populus
      tremuloides, spalted P. tremuloides, and Ailanthus altissima), stimulated colony
      growth and xylindein production in C. aeruginascens. Addition of any amount of
      wood produced more growth than no wood additions, while ground wood produced more
      growth than chopped wood. Of the wood types tested, A. saccharum wood stimulated
      all four isolates, while spalted Populus tremuloides stimulated three of the four
      isolates. High glucose and sucrose amounts may be partially responsible for the
      greater stimulatory affect of some woods over others. The development of this
      simple and reliable method for growth and pigment stimulation of C. aeruginascens
      in laboratory conditions will allow for further development of this fungus for
      decorative and commercial use.

PMID- 22409932
TI  - Membrane vesicle release in bacteria, eukaryotes, and archaea: a conserved yet
      underappreciated aspect of microbial life.
AB  - Interaction of microbes with their environment depends on features of the dynamic
      microbial surface throughout cell growth and division. Surface modifications,
      whether used to acquire nutrients, defend against other microbes, or resist the
      pressures of a host immune system, facilitate adaptation to unique surroundings.
      The release of bioactive membrane vesicles (MVs) from the cell surface is
      conserved across microbial life, in bacteria, archaea, fungi, and parasites. MV
      production occurs not only in vitro but also in vivo during infection,
      underscoring the influence of these surface organelles in microbial physiology
      and pathogenesis through delivery of enzymes, toxins, communication signals, and
      antigens recognized by the innate and adaptive immune systems. Derived from a
      variety of organisms that span kingdoms of life and called by several names
      (membrane vesicles, outer membrane vesicles [OMVs], exosomes, shedding
      microvesicles, etc.), the conserved functions and mechanistic strategies of MV
      release are similar, including the use of ESCRT proteins and ESCRT protein
      homologues to facilitate these processes in archaea and eukaryotic microbes.
      Although forms of MV release by different organisms share similar visual,
      mechanistic, and functional features, there has been little comparison across
      microbial life. This underappreciated conservation of vesicle release, and the
      resulting functional impact throughout the tree of life, explored in this review,
      stresses the importance of vesicle-mediated processes throughout biology.

PMID- 22409933
TI  - Dysfunction of natural killer T cells in patients with active Mycobacterium
      tuberculosis infection.
AB  - Natural killer T (NKT) cells are known to play a protective role in the immune
      responses of mice against a variety of infectious pathogens. However, little is
      known about the detailed information of NKT cells in patients with Mycobacterium
      tuberculosis infection. The aims of this study were to examine NKT cell levels
      and functions in patients with active M. tuberculosis infection, to investigate
      relationships between NKT cell levels and clinical parameters, and to determine
      the mechanism responsible for the poor response to alpha-galactosylceramide
      (alpha-GalCer). NKT cell levels were significantly lower in the peripheral blood
      of pulmonary tuberculosis and extrapulmonary tuberculosis patients, and the
      proliferative responses of NKT cells to alpha-GalCer were also lower in patients,
      whereas NKT cell levels and responses were comparable in latent tuberculosis
      infection subjects and healthy controls. Furthermore, this NKT cell deficiency
      was found to be correlated with serum C-reactive protein levels. In addition, the
      poor response to alpha-GalCer in M. tuberculosis-infected patients was found to
      be due to increased NKT cell apoptosis, reduced CD1d expression, and a defect in
      NKT cells. Notably, M. tuberculosis infection was associated with an elevated
      expression of the inhibitory programmed death-1 (PD-1) receptor on NKT cells, and
      blockade of PD-1 signaling enhanced the response to alpha-GalCer. This study
      shows that NKT cell levels and functions are reduced in M. tuberculosis-infected
      patients and these deficiencies were found to reflect the presence of active
      tuberculosis.

PMID- 22409934
TI  - Peptide immunotherapy for childhood allergy - addressing translational
      challenges.
AB  - Allergic sensitisation usually begins early in life. The number of allergens a
      patient is sensitised to can increase over time and the development of additional
      allergic conditions is increasingly recognised. Targeting allergic disease in
      childhood is thus likely to be the most efficacious means of reducing the overall
      burden of allergic disease. Specific immunotherapy involves administering protein
      allergen to tolerise allergen reactive CD4+ T cells, thought key in driving
      allergic responses. Yet specific immunotherapy risks allergic reactions including
      anaphylaxis as a consequence of preformed allergen-specific IgE antibodies
      binding to the protein, subsequent cross-linking and mast cell degranulation.
      CD4+ T cells direct their responses to short "immunodominant" peptides within the
      allergen. Such peptides can be given therapeutically to induce T cell tolerance
      without facilitating IgE cross-linking. Peptide immunotherapy (PIT) offers
      attractive treatment potential for allergic disease. However, PIT has not yet
      been shown to be effective in children. This review discusses the immunological
      mechanisms implicated in PIT and briefly covers outcomes from adult PIT trials.
      This provides a context for discussion of the challenges for the application of
      PIT, both generally and more specifically in relation to children.

PMID- 22409935
TI  - Course of mental symptoms in patients with stress-related exhaustion: does sex or
      age make a difference?
AB  - BACKGROUND: Long-term sick leave due to mental health problems, especially among
      women, is a substantial problem in many countries, and a major reason for this is
      thought to be psychosocial stress. The recovery period of different patient
      groups with stress-related mental health problems can differ considerably. We
      have studied the course of mental health symptoms during 18 months of multimodal
      treatment in relation to sex and age in a group of patients with stress-related
      exhaustion. METHODS: The study group includes 232 patients (68% women) referred
      to a stress clinic and who fulfilled the criteria for Exhaustion Disorder (ED).
      The majority also fulfilled diagnostic criteria for depression and/or anxiety;
      this was similar among women and men. Symptoms were assessed at baseline, three,
      six, 12 and 18 months by the Shirom-Melamed Burnout Questionnaire (SMBQ) and the
      Hospital Anxiety and Depression scale (HAD). A total SMBQ mean score of >= 4 was
      used to indicate clinical burnout, which correlates well with the clinical
      diagnosis of ED. RESULTS: There were no statistically significant differences
      between women and men or between young and old patients in the self-reported
      symptoms at baseline. The proportion that had high burnout scores decreased over
      time, but one-third still had symptoms of clinical burnout after 18 months.
      Symptoms indicating probable depression or anxiety (present in 34% and 65% of the
      patients at baseline, respectively) declined more rapidly, in most cases within
      the first three months, and were present only in one out of 10 after 18 months.
      The course of illness was not related to sex or age. The duration of symptoms
      before seeking health care, but not the level of education or co-morbid
      depression, was a predictor of recovery from symptoms of burnout after 18 months.
      CONCLUSIONS: The course of mental illness in patients seeking specialist care for
      stress-related exhaustion was not related to sex or age. The burden of mental
      symptoms is high and similar for men and women, and at the 18 month follow-up,
      one-third of the study group still showed symptoms of burnout. A long duration of
      symptoms before consultation was associated with a prolonged time of recovery,
      which underlines the importance of early detection of stress-related symptoms.

PMID- 22409936
TI  - Organization in autism.

PMID- 22409937
TI  - Progressive gait deterioration in adolescents with Dravet syndrome.
AB  - OBJECTIVE: To characterize changes in gait by age in patients with Dravet
      syndrome. DESIGN: Prospective, cross-sectional study. SETTING: Tertiary
      children's hospital. PATIENTS: Twenty-six subjects with Dravet syndrome, aged 2
      to 34 years. Twenty-three patients had mutations of the sodium channel alpha1
      subunit gene, SCN1A. INTERVENTIONS: Assessment via video gait analysis, physical
      examination of the lower limbs, use of the Functional Mobility Scale, and
      radiographs of the pelvis and feet. MAIN OUTCOME MEASURES: Classification of the
      sagittal gait pattern and foot posture, assessment of muscle extensibility and
      joint range, and rating of functional mobility. RESULTS: Children aged 0 to 5
      years had a normal or near-normal gait, whereas 5 of 10 children aged 6 to 12
      years and 8 of 9 children aged 13 years or older had crouch gait. Physical
      examination showed that with increasing age, passive knee extension (P = .008)
      and hip extension (P = .003) decreased, external tibial torsion (P = .007) and
      pes planovalgus (P = .05) increased, and increased hip internal rotation did not
      show age-related change (P = .27). The Functional Mobility Scale showed universal
      independent walking over 5 and 50 m; however, adolescents showed wide variation
      in their ratings over 500 m, indicating mobility ranging from wheelchair use to
      independent walking (P = .02). CONCLUSIONS: Children with Dravet syndrome show
      progressive gait deterioration in the second decade of life, with crouch gait and
      skeletal malalignment comprising increased femoral neck anteversion, external
      tibial torsion, and pes valgus. These age-related changes have a significant
      impact on mobility and independence in the community setting.

PMID- 22409938
TI  - "Blinding" empty sella: can lumbar puncture be avoided?

PMID- 22409939
TI  - Shapes of the trajectories of 5 major biomarkers of Alzheimer disease.
AB  - OBJECTIVE: To characterize the shape of the trajectories of Alzheimer disease
      biomarkers as a function of Mini-Mental State Examination (MMSE) score. DESIGN
      AND SETTING: Longitudinal registries from the Mayo Clinic and the Alzheimer's
      Disease Neuroimaging Initiative. PATIENTS: Two different samples (n = 343 and n =
      598) were created that spanned the cognitive spectrum from normal to Alzheimer
      disease dementia. Subgroup analyses were performed in members of both cohorts (n
      = 243 and n = 328) who were amyloid positive at baseline. MAIN OUTCOME MEASURES:
      The shape of biomarker trajectories as a function of MMSE score, adjusted for
      age, was modeled and described as baseline (cross-sectional) and within-subject
      longitudinal effects. Biomarkers evaluated were cerebrospinal fluid (CSF) Abeta42
      and tau levels, amyloid and fluorodeoxyglucose positron emission tomography
      imaging, and structural magnetic resonance imaging. RESULTS: Baseline biomarker
      values generally worsened (ie, nonzero slope) with lower baseline MMSE score.
      Baseline hippocampal volume, amyloid positron emission tomography, and
      fluorodeoxyglucose positron emission tomography values plateaued (ie, nonlinear
      slope) with lower MMSE score in 1 or more analyses. Longitudinally, within
      subject rates of biomarker change were associated with worsening MMSE score.
      Nonconstant within-subject rates (deceleration) of biomarker change were found in
      only 1 model. CONCLUSIONS: Biomarker trajectory shapes by MMSE score were complex
      and were affected by interactions with age and APOE status. Nonlinearity was
      found in several baseline effects models. Nonconstant within-subject rates of
      biomarker change were found in only 1 model, likely owing to limited within
      subject longitudinal follow-up. Creating reliable models that describe the full
      trajectories of Alzheimer disease biomarkers will require significant additional
      longitudinal data in individual participants.

PMID- 22409940
TI  - Exonic deletions of FXN and early-onset Friedreich ataxia.
AB  - BACKGROUND: Friedreich ataxia (FA) is the most frequent type of autosomal
      recessive cerebellar ataxia, occurring at a mean age of 16 years. Nearly 98% of
      patients with FA present with homozygous GAA expansions in the FXN gene. The
      remaining patients are compound heterozygous for an expansion and a point
      mutation. Patients who are compound heterozygous for an exonic deletion and an
      expansion are exquisitely rare. OBJECTIVES: To describe 6 patients affected with
      FA due to an exonic deletion mutation (FAexdel) and to compare these 6 patients
      with FAexdel with 46 patients consecutively diagnosed with typical FA due to
      homozygous GAA expansion and whose small expansions were within the same range as
      that of the expansions of the patients with FAexdel. DESIGN: Description of a
      series. SETTING: Academic research. PATIENTS: Six patients with FAexdel and 46
      patients with typical FA. INTERVENTION: FXN gene analysis, including assessments
      of GAA expansion and exon sequencing and determination of exonic copy numbers
      using multiplex ligation-dependent probe amplification. RESULTS: We identified 6
      patients with FA who presented with the combination of 1 GAA expansion and 1 FXN
      exonic deletion. The mean (SD) age at onset of the disease was earlier for
      patients with FAexdel (7 [4] years [range, 3-12 years]) than for patients with
      typical FA (15 [5] years [range, 6-30 years]) (P = .001), and the median time to
      confinement to wheelchair was shorter for patients with FAexdel (20 years) than
      for patients with typical FA (28 years) (P = .002). There was no difference
      between the mean (SD) size of the expansion for the patients with FAexdel (780
      [256] GAA triplet repeat sequences [range, 340-1070 GAA triplet repeat
      sequences]) and the mean (SD) size of the short expansion for the patients with
      typical FA (634 [163] GAA triplet repeat sequences [range, 367-1000 GAA triplet
      repeat sequences]) (P = .10). The mean disease duration before becoming
      wheelchair bound was shorter for patients with FAexdel (9 years) than for
      patients with typical FA (13 years), and the incidence of cardiomyopathy was
      higher for patients with FAexdel (84%) than for patients with typical FA (68%).
      However, these differences were not significant, probably owing to the small size
      of the FAexdel group. The other extraneurological signs, such as scoliosis or
      diabetes mellitus, were particularly frequently observed in the FAexdel group.
      One patient presented at 9 years of age with severe angina and marked
      cardiomyopathy that confined her to a wheelchair. Three patients had disabling
      autonomic disturbances. It appears that exonic deletion significantly contributes
      to the clinical picture of patients with FA. CONCLUSIONS: Friedreich ataxia due
      to an exonic deletion mutation corresponds to an early onset and severe variant
      of FA. FXN should be investigated for exonic deletion in patients with early
      onset FA in which only 1 GAA expansion without a point mutation is found.
      Patients with FAexdel have to be carefully observed using cardiological,
      orthopaedic, endocrinological, gastroenterological, and ophthalmological data.
      Friedreich ataxia due to an exonic deletion mutation should be suspected in young
      patients presenting with severe scoliosis.

PMID- 22409941
TI  - 3,4-Diaminopyridine improves neuromuscular transmission in a MuSK antibody
      induced mouse model of myasthenia gravis.
AB  - This study investigated the effect of 3,4-diaminopyridine (3,4-DAP), a potent
      potentiator of transmitter release, on neuromuscular transmission in vivo in a
      mouse model of myasthenia gravis (MG) caused by antibodies against muscle
      specific kinase (MuSK; MuSK-MG) and ex vivo in diaphragm muscle from these mice.
      3,4-DAP significantly improved neuromuscular transmission, predominantly by
      increasing acetylcholine (ACh) release, supporting presynaptic potentiation as an
      effective treatment strategy for MuSK-MG patients who have defective transmitter
      release. In MuSK-MG, we suggest that only low-dose acetylcholinesterase (AChE)
      inhibitors be used to avoid side effects, and we propose that 3,4-DAP may be
      effective as a symptomatic therapy.

PMID- 22409942
TI  - Dynamic regulatory on/off minimization for biological systems under internal
      temporal perturbations.
AB  - BACKGROUND: Flux balance analysis (FBA) together with its extension, dynamic FBA,
      have proven instrumental for analyzing the robustness and dynamics of metabolic
      networks by employing only the stoichiometry of the included reactions coupled
      with adequately chosen objective function. In addition, under the assumption of
      minimization of metabolic adjustment, dynamic FBA has recently been employed to
      analyze the transition between metabolic states. RESULTS: Here, we propose a
      suite of novel methods for analyzing the dynamics of (internally perturbed)
      metabolic networks and for quantifying their robustness with limited knowledge of
      kinetic parameters. Following the biochemically meaningful premise that
      metabolite concentrations exhibit smooth temporal changes, the proposed methods
      rely on minimizing the significant fluctuations of metabolic profiles to predict
      the time-resolved metabolic state, characterized by both fluxes and
      concentrations. By conducting a comparative analysis with a kinetic model of the
      Calvin-Benson cycle and a model of plant carbohydrate metabolism, we demonstrate
      that the principle of regulatory on/off minimization coupled with dynamic FBA can
      accurately predict the changes in metabolic states. CONCLUSIONS: Our methods
      outperform the existing dynamic FBA-based modeling alternatives, and could help
      in revealing the mechanisms for maintaining robustness of dynamic processes in
      metabolic networks over time.

PMID- 22409943
TI  - Nonpain goal pursuit inhibits attentional bias to pain.
AB  - Although dealing with pain is a vital goal to pursue, most individuals are also
      engaged in the pursuit of other goals. The aim of the present experiment was to
      investigate whether attentional bias to pain signals is inhibited when one is
      pursuing a concurrent salient but nonpain task goal. Attentional bias to pain
      signals was measured in pain-free volunteers (n=63) using a spatial cueing task
      with pain cues and neutral cues. The pursuit of a concurrent goal was manipulated
      by including additional trials in which a digit appeared at the middle of the
      screen. Half of the participants (goal group) were instructed to name these
      additional stimuli aloud. In order to increase the affective-motivational value
      of this non-pain-related goal, monetary reward and punishment were made
      contingent upon the performance of this task. Participants of the control group
      did not perform the additional task. As predicted, the results show attentional
      bias to pain signals in the control group, but not in the goal group. This
      indicates that attentional bias to signals of impending pain is inhibited when
      one is engaged in the pursuit of another salient but nonpain goal. The results of
      this study underscore a motivational view on attention to pain, in which the
      pursuit of multiple goals, including nonpain goals, is taken into account.

PMID- 22409944
TI  - Lipid shape is a key factor for membrane interactions of amphipathic helical
      peptides.
AB  - The membrane alignment of the amphiphilic alpha-helical model peptide MSI-103
      (sequence [KIAGKIA]3-NH2) was examined by solid state 2H-NMR in different lipid
      systems by systematically varying the acyl chain length and degree of saturation,
      the lipid head group type, and the peptide-to-lipid molar ratio. In liquid
      crystalline phosphatidylcholine (PC) lipids with saturated chains, the
      amphiphilic helix changes its orientation from a surface-bound "S-state" to a
      tilted "T-state" with increasing peptide concentration. In PC lipids with
      unsaturated chains, on the other hand, the S-state is found throughout all
      concentrations. Using phosphatidylethanolamine lipids with a small head group or
      by addition of lyso-lipids with only one acyl chain, the spontaneous curvature of
      the bilayer was purposefully changed. In the first case with a negative curvature
      only the S-state was found, whereas in systems with a positive curvature the
      peptide preferred the obliquely immersed T-state at high concentration. The
      orientation of MSI-103 thus correlates very well with the shape of the lipid
      molecules constituting the membrane. Lipid charge, on the other hand, was found
      to affect only the initial electrostatic attraction to the membrane surface but
      not the alignment preferences. In bilayers that are "sealed" with 20%
      cholesterol, MSI-103 cannot bind in a well-oriented manner and forms immobilized
      aggregates instead. We conclude that the curvature properties of a membrane are a
      key factor in the interactions of amphiphilic helical peptides in general, whose
      re-alignment and immersion preferences may thus be inferred in a straightforward
      manner from the lipid-shape concept.

PMID- 22409945
TI  - Low fatness, reduced fat intake and adequate plasmatic concentrations of LDL
      cholesterol are associated with high bone mineral density in women: a cross
      sectional study with control group.
AB  - BACKGROUND: Several parameters are associated with high bone mineral density
      (BMD), such as overweight, black background, intense physical activity (PA),
      greater calcium intake and some medications. The objectives are to evaluate the
      prevalence and the main aspects associated with high BMD in healthy women.
      METHODS: After reviewing the database of approximately 21,500 BMD scans performed
      in the metropolitan area of Sao Paulo, Brazil, from June 2005 to October 2010,
      high BMD (over 1400 g/cm2 at lumbar spine and/or above 1200 g/cm2 at femoral
      neck) was found in 421 exams. Exclusion criteria were age below 30 or above 60
      years, black ethnicity, pregnant or obese women, disease and/or medications known
      to interfere with bone metabolism. A total of 40 women with high BMD were
      included and matched with 40 healthy women with normal BMD, paired to weight,
      age, skin color and menopausal status. Medical history, food intake and PA were
      assessed through validated questionnaires. Body composition was evaluated through
      a GE-Lunar DPX MD + bone densitometer. Radiography of the thoracic and lumbar
      spine was carried out to exclude degenerative alterations or fractures.
      Biochemical parameters included both lipid and hormonal profiles, along with
      mineral and bone metabolism. Statistical analysis included parametric and
      nonparametric tests and linear regression models. P < 0.05 was considered
      significant. RESULTS: The mean age was 50.9 (8.3) years. There was no significant
      difference between groups in relation to PA, smoking, intake of calcium and
      vitamin D, as well as laboratory tests, except serum C-telopeptide of type I
      collagen (s-CTX), which was lower in the high BMD group (p = 0.04). In the final
      model of multivariate regression, a lower fat intake and body fatness as well a
      better profile of LDL-cholesterol predicted almost 35% of high BMD in women.
      (adjusted R2 = 0.347; p < 0.001). In addition, greater amounts of lean mass and
      higher IGF-1 serum concentrations played a protective role, regardless age and
      weight. CONCLUSION: Our results demonstrate the potential deleterious effect of
      lipid metabolism-related components, including fat intake and body fatness and
      worse lipid profile, on bone mass and metabolism in healthy women.

PMID- 22409946
TI  - The pharmacogenetic background of hepatitis C treatment.
AB  - Insufficiently treated hepatitis C virus (HCV) infection remains a major
      healthcare issue. Individual therapy responses vary considerably from spontaneous
      clearing of the virus to lethal conditions. Host genetics currently receives a
      major scientific and clinical interest as an important source of interindividual
      variability in treatment. Mainly the associations of interleukin 28B gene (IL28B)
      variants with decreased HCV clearance under standard therapy are considered as
      "state of the art" of hepatitis C pharmacogenetics. However, a search in PubMed
      identified 41 genes reportedly modulating the individual therapy response, e.g.,
      genes coding for major histocompatibility complex (HLA), the tumor necrosis
      factor (TNF), interleukin 10 (IL10), other interferon coding genes than IL28B
      (e.g., IFNAR1, IFNAR2, IFNG), several components of downstream interferon
      signaling as well as genes modulating side effects of current anti-HCV
      therapeutics (e.g., SLC28A3, ITPA involved in ribavirin associated hemolytic
      effects or SLC6A4 and HTR1A involved in serotonin associated psychiatric side
      effects). Applying knowledge discovery methods from the area of data mining and
      machine-learning to this comprehensive set of HCV therapy modulating genes,
      relating the HCV genes to the world wide knowledge on genes given in the form of
      the Gene Ontology (GO) knowledge base, found that the relevant genes belong to
      the GO subcategories of "inflammatory response" and "immune response" and
      "response to virus". This complex approaches to the pharmacogenomics of HCV may
      serve to identify future candidates for a personalization of HCV therapy and
      structured approach to possible new therapeutic targets for the control of
      hepatitis C virus.

PMID- 22409947
TI  - Bisphosphonates combined with sunitinib may improve the response rate,
      progression free survival and overall survival of patients with bone metastases
      from renal cell carcinoma.
AB  - BACKGROUND: Bisphosphonates are used to prevent skeletal events of bone
      metastases, and may exhibit antitumour effects. We aimed to evaluate whether
      bisphosphonates can bring a response rate (RR), progression free survival (PFS)
      and overall survival (OS) benefit to patients with bone metastasis from renal
      cell carcinoma (RCC) that is treated with sunitinib. METHODS: We performed a
      multicentre retrospective study of patients with bone metastases from RCC that
      was treated with sunitinib. The effect of bisphosphonates on RR, PFS and OS was
      tested with adjustment for known prognostic factors using a chi-square test from
      contingency table and partial likelihood test from Cox regression model. RESULTS:
      Between 2004 and 2011, 209 patients with metastatic RCC were treated with
      sunitinib, 76 had bone metastases, 35 bisphosphonates users and 41 non-users. The
      groups of bisphosphonates users and non-users were balanced regarding known
      prognostic factors. Objective response was partial response/stable disease 86% (n
      = 30) versus 71% (n = 29), and progressive disease 14% (n = 5) versus 29% (n =
      12) (p = 0.125, OR 2.48) in users versus non-users, respectively. Median PFS was
      15 versus 5 months (HR = 0.55, p<0.0001), and median OS was not reached (with a
      median follow-up time of 45 months) versus 14 months (HR = 0.4, p = 0.029), in
      favour of users. In multivariate analysis of the entire patient cohort (n = 76),
      factors associated with PFS were bisphosphonates use (HR = 0.58, p = 0.035), and
      pre-treatment neutrophil to lymphocyte ratio >3 (HR = 3.5, p = 0.009). Factors
      associated with OS were bisphosphonates use (HR = 0.5, p = 0.008), elevated pre
      treatment alkaline phosphatase (HR = 2.9, p = 0.003) and sunitinib induced HTN
      (HR = 0.63, p<0.0001). CONCLUSIONS: Bisphosphonates may improve the RR, PFS and
      OS of sunitinib treatment in RCC with bone metastases.

PMID- 22409948
TI  - Comparison of 4 femoral tunnel drilling techniques in anterior cruciate ligament
      reconstruction.
AB  - PURPOSE: The purpose of this study was to determine which femoral tunnel drilling
      technique most closely reproduces the anatomic femoral footprint and has
      acceptable tunnel length and tunnel orientation. METHODS: We divided 20 cadaveric
      knees into 4 equal groups. Arthroscopically, the anatomic femoral footprint was
      marked with an awl as the tunnel starting point. In group 1 the femoral tunnel
      was drilled through a tibial tunnel. In groups 2 and 3 the femoral tunnel was
      drilled through the anteromedial arthroscopy portal, with a rigid drill and
      flexible drill, respectively. In group 4 the femoral tunnel was drilled with the
      outside-in technique over a pin positioned with an arthroscopic femoral guide.
      Measurements of the tunnel length, aperture, and placement were taken from 3
      dimensional computed tomography scans. RESULTS: Tunnel length for groups 1, 2, 3,
      and 4 averaged 42.08 mm, 37.73 mm, 28.92 mm, and 31.96 mm (P = .039). The mean
      coronal angle of the tunnels as measured from the line tangent to the posterior
      femoral condyles was 63.30 degrees , 61.22 degrees , 51.77 degrees , and 45.00
      degrees  (P = .007), and the mean distance from the inferior articular surface to
      the edge of the tunnel was 5.60 mm, 4.36 mm, 2.42 mm, and -0.63 mm (P = .008) for
      groups 1, 2, 3, and 4, respectively. There was no statistical difference in
      footprint length, width, area, or distance from the posterior articular margin.
      CONCLUSION: Drilling by the transtibial technique produces the most vertical and
      longest tunnels. Independent drilling techniques produce the most anatomic
      tunnels but at the expense of tunnel length. CLINICAL RELEVANCE: When the
      orthopaedic surgeon is performing ACL reconstruction, it is critical to achieve
      anatomic placement of the graft, as well as maintain appropriate tunnel length.

PMID- 22409949
TI  - Kerasoft IC compared to Rose-K in the management of corneal ectasias.
AB  - PURPOSE: To determine the efficacy of the KeraSoft((r)) IC (KIC) (Ultravision
      International Limited, Bedfordshire, UK), a silicone hydrogel contact lens, for
      the optical management of non-surgical corneal ectasias and to compare it with
      the Rose-K 2 RGP contact lens. METHODS: In a retrospective study ninety-four eyes
      fitted with KIC (group A) were compared with seventy-seven eyes fitted with Rose
      K((r)) RGP lenses as a control group. Ocular diagnoses, corneal curvature by
      topography, refraction, best spectacle-corrected visual acuity (BSCVA), and age
      at time of fitting were noted. Outcome data included average daily wearing time,
      contact lens complications, visual acuity with the lens (BCLCVA), power of the
      lenses and length of follow-up. RESULTS: Differences in either BCLCVA or wearing
      time could not be statistically established (p = 0.63, p = 0.15) between both
      groups. More biomicroscopic complications were found in the RGP group, basically
      corneal staining (P < 0.0001). In the KIC group, BCLCVA was statistically similar
      between types of ectasia (p = 0.19) as well as in mild and moderate keratoconus
      (p = 0.45). CONCLUSIONS: KIC is a good alternative for the optical management of
      irregular corneal astigmatism in non surgical corneal ectasias such as
      keratoconus and pellucid marginal degeneration.

PMID- 22409950
TI  - Fibre optics sensors in tear electrolyte analysis: towards a novel point of care
      potassium sensor.
AB  - The diagnosis of ocular disease is increasingly important in optometric practice
      and there is a need for cost effective point of care assays to assist in that.
      Although tears are a potentially valuable source of diagnostic information
      difficulties associated with sample collection and limited sample size together
      with sample storage and transport have proved major limitations. Progressive
      developments in electronics and fibre optics together with innovation in sensing
      technology mean that the construction of inexpensive point of care fibre optic
      sensing devices is now possible. Tear electrolytes are an obvious family of
      target analytes, not least to complement the availability of devices that make
      the routine measurement of tear osmolarity possible in the clinic. In this paper
      we describe the design, fabrication and calibration of a fibre-optic based
      electrolyte sensor for the quantification of potassium in tears using the ex vivo
      contact lens as the sample source. The technology is generic and the same
      principles can be used in the development of calcium and magnesium sensors. An
      important objective of this sensor technology development is to provide
      information at the point of routine optometric examination, which would provide
      supportive evidence of tear abnormality.

PMID- 22409951
TI  - [Antibiotics and timing in infectious disease in the emergency department].
AB  - Infectious diseases, besides being a major cause of mortality in developing
      countries, are one of the main reasons for consultation in emergency medicine. In
      the last few years, there have been numerous published studies on the importance
      of starting antibiotic treatment at an early stage in the Emergency Department.
      However, this issue is of great controversy, owing to some contradictory studies
      as well as the implications this may have on the pressure of the patient care.
      This review is presents a summary of the scientific evidence published in this
      regard, and makes some recommendations based on this published evidence to
      improve the initial management of patients with an infection; a question of great
      importance as it can reduce mortality in some specific situations.

PMID- 22409953
TI  - [Microbiological diagnosis of intra-abdominal infections].
AB  - Intra-abdominal infections represent a large and wide group of diseases which
      include intra- and retro-peritoneal infections. Some of them could be defined as
      uncomplicated, where the infectious process is limited to the organ or tissue of
      origin (appendicitis, diverticulitis, cholecystitis...). Complications occur when
      the infection spreads to the peritoneum, triggering localised peritonitis and
      abdominal abscesses. Most intra-abdominal infections are due to perforation or
      inflammation of the intestinal wall. The microorganisms that cause these
      infections come from the gastrointestinal flora, and therefore produce
      polymicrobial infections mixed with a predominance of anaerobic bacteria.
      Microbiological diagnosis is essential to determine the aetiology and the
      susceptibility of antimicrobial agents of the microorganism involved, especially
      in nosocomial infections or in community infections in predisposed patients due
      to increasing bacterial resistance to antimicrobial agents, multidrug resistance
      and fungal involvement. Despite the advances in microbiological diagnosis, in the
      case of intra-abdominal infections it still remains direct, being based on stains
      and cultures, the most notable progress is the introduction of mass spectrometry
      (MALDI-TOF) for the rapid identification of the pathogens involved. This review
      will provide recommendations on the collection, transport and microbiological
      processing of clinical specimens. Comments on the pathogenesis, clinical and
      microbiological diagnosis of peritonitis primary, secondary, tertiary and
      peritonitis (and other infections) associated with peritoneal dialysis, intra
      abdominal abscesses (intraperitoneal, retroperitoneal and visceral), biliary
      tract infections, appendicitis and diverticulitis are also presented.

PMID- 22409952
TI  - [Imported diseases by immigrants and travellers: results from the Cooperative
      Network for the study of Imported Diseases by Immigrants and Travellers +Redivi].
AB  - INTRODUCTION: Imported diseases by travellers and immigrants are a priority in
      the prevention of emerging infectious diseases in the 21st century. There are
      international records on imported diseases, but no such records are available in
      Spain. MATERIAL AND METHODS: The cooperative network +Redivi was created in 2009
      and consists of 11 national healthcare centres. +Redivi collects demographic data
      relating to travel/migration and infectious diseases in brief, computerised
      forms. RESULTS: From January 2009 to October 2011, we collected 4,570 patients
      and recorded the main demographic data (age, sex, presence of immunosuppression),
      travel data (destination, duration, time between the return trip and the
      consultation) and data regarding the migratory process (country of origin, time
      between the arrival in Spain and the first consultation), as well as preventive
      measures that have been taken (pre-travel advice, need for malaria
      chemoprophylaxis, drug that was used and whether it was correct), the reason for
      coming to the consultation, and final diagnoses of the travellers, immigrants and
      immigrants-travellers. Likewise, the most frequent diagnoses of asymptomatic
      patients who came for a check-up are described for each of the three groups.
      CONCLUSIONS: The +Redivi network allows us to identify and quantify the
      geographical origin and the type of patients affected, as well as time pattern of
      infections imported by migrants and travellers. Preliminary data show the
      significant presence of transmissible diseases and the potential reintroduction
      in Spain, as well as the importance of systematic screening in patients that came
      from tropical areas. The objective of +Redivi is to evaluate the impact of
      imported diseases in Spain in order to contribute to improving the care of
      patients, to have an influence on prevention and treatment of the most prevalent
      imported diseases, and to detect possible outbreaks.

PMID- 22409954
TI  - Diagnostic potential of Fasciola gigantica-derived 14.5 kDa fatty acid binding
      protein in the immunodiagnosis of bubaline fascioliasis.
AB  - The 14.5 kDa fatty acid binding protein (FABP) was isolated from the crude
      extract of adult Fasciola gigantica worms. Polyclonal anti-FABP IgG was generated
      in rabbits immunized with prepared FABP antigen. Sandwich enzyme-linked
      immunosorbent assay (ELISA) was applied to detect coproantigen in stools and
      circulating Fasciola antigen (CA) in sera of 126 water buffaloes by using
      purified and horseradish peroxidase (HRP)-conjugated anti-FABP IgG. Sandwich
      ELISA sensitivity was 96.97% and 94.95%; while specificity was 94.12% and 82.35%
      for coproantigen and CA detection, respectively. However, sensitivity and
      specificity of the Kato-Katz technique was 73.74% and 100%, respectively. The
      diagnostic efficacy of sandwich ELISA was 96.55% and 93.1% for coproantigen and
      CA detection, respectively. In contrast, the diagnostic efficacy of the Kato-Katz
      technique was 77.59%. In conclusion, these results demonstrate that the purified
      14.5 kDa FABP provides a more suitable antigen for immunodiagnosis of early and
      current bubaline fascioliasis by using sandwich ELISA.

PMID- 22409955
TI  - Lung function in children and adolescents with juvenile idiopathic arthritis
      during long-term treatment with methotrexate: a retrospective study.
AB  - OBJECTIVES: Methotrexate may cause severe adverse pulmonary side-effects in
      adults with rheumatoid arthritis. Our aim was to examine the long-term effect of
      MTX on lung function in patients with juvenile idiopathic arthritis (JIA).
      METHODS: We retrospectively reviewed the charts of all 68 patients with JIA
      treated with MTX at our centre over a 14-year period. Results of annual pulmonary
      function tests (PFT) were compared using paired t-tests adjusted by Bonferroni
      correction and by linear regression analysis. RESULTS: The patients in our study
      had taken MTX for a median of 6.7 years with a median cumulative dose of 3219 mg.
      In a subgroup of 37 patients PFT had been performed before the onset of MTX. In
      this subgroup there was a significant decrease of mean mid-expiratory flow (MMEF)
      after 3 years (-14.0%, p<0.001) of MTX. Diffusion capacity of the lung for carbon
      monoxide (DLCO) was reduced after the third year (-12.4%, p=0.001). In the total
      group there was a decrease in MMEF between years 3 and 4 after MTX onset (-13.5%,
      p=0.001). Forced expiratory volume (FEV1) showed a slight rise between years 4
      and 5 (+5.5%, p=0.003). All other parameters remained without significant
      changes. There was no correlation of PFT results and cumulative MTX dose or JIA
      subtype. None of our patients developed clinically relevant lung disease.
      CONCLUSIONS: In summary we found some declines of MMEF and DLCO during long-term
      treatment with MTX. Overall our data confirm the relative safety of long-term MTX
      treatment in patients with JIA. We conclude that further data on the development
      of pulmonary function in patients receiving MTX therapy would be helpful.

PMID- 22409956
TI  - Peak expiratory flow as a screening tool to detect airflow obstruction in a
      primary health care setting.
AB  - BACKGROUND: Peak expiratory flow (PEF) measurement is less expensive and requires
      fewer skills than spirometry testing. It is thus expected to be a reasonable
      substitute for spirometry in airflow obstruction screening when spirometry is
      unavailable. OBJECTIVES: To evaluate the validation  of PEF measurement in the
      detection of airflow obstruction using newly established regression equations.
      METHODS: The PEFs of 553 'normal' participants aged 40-85 years were measured
      using mechanical devices. Based on these data, regression equations were
      generated to  predict normal PEF values. Data were then collected from 3379
      subjects. The specificity and sensitivity of the different predicted PEF cut-off
      points for detecting airflow obstruction were evaluated by spirometry, based on
      previously generated regression equations. RESULTS: Using newly  established
      reference values for PEF, PEF had higher sensitivity and specificity than the
      questionnaire in detection of airflow obstruction. That PEF < 80% of predicted
      was more effective in the detection of airflow obstruction was confirmed by the
      lower limit of normal of forced expiratory  volume in 1 second/forced vital
      capacity, Global Initiative for Chronic Obstructive Lung Disease (GOLD), and GOLD
      plus symptom, with a sensitivity of 78.7%, 76.8%, 85.3% and a specificity of
      81.9%, 83.8%, 81.4%, respectively. CONCLUSIONS: Mechanical PEF may be a
      reasonable method of screening  for airflow obstruction in settings where
      spirometry is unavailable.

PMID- 22409958
TI  - Applying mean shift, motion information and Kalman filtering approaches to object
      tracking.
AB  - Contemporary research is developing techniques to tracking objects in videos
      using color features, and the mean shift (MS) algorithm is one of the best. This
      known algorithm is employed to find the location of an object, in image sequence,
      by using a coefficient called the Bhattacharyya coefficient. This coefficient is
      calculated through an object tracking algorithm to present the similarity in
      appearance between an object and its candidate model, where the best
      representation of an object is acquired, once this is could be maximized.
      However, the MS algorithm performance is confounded by color clutter in
      background, various illuminations, occlusion types and other related limitations.
      Because of such effects, the algorithm necessarily decreases the value of the
      Bhattacharyya coefficient, indicating reduced certainty in the object tracking.
      In the present research, an improved convex kernel function is proposed to
      overcome the partial occlusion. Afterwards, in order to improve the MS algorithm
      against the low saturation and also sudden light, changes are made from motion
      information of the desired sequence. By using both the color feature and the
      motion information simultaneously, the capability of the MS algorithm is
      correspondingly increased, in the present approach. Moreover, by assuming a
      constant speed for the object, a robust estimator, i.e., the Kalman filter, is
      realized to solve the full occlusion problem. At the end, experimental results on
      various videos verify that the proposed method has an optimum performance in real
      time object tracking, while the result of the original MS algorithm may be
      unsatisfied.

PMID- 22409957
TI  - Psychiatric disorders and aggression in the printed media: is there a link? A
      central European perspective.
AB  - BACKGROUND: A content analysis was used to describe the association between
      psychiatric disorders and aggression in the printed media in the Czech Republic
      and Slovakia. METHODS: Articles were chosen from the most widely read daily
      newspapers and magazines in both countries during five one-week periods in 2007.
      A coding manual was developed and a content analysis was performed. Aggressive
      behavior was assessed by two separate categories - the role of the mentally ill
      person in the violent act (perpetrator/victim) and the type of aggressive act
      (homicide, suicide). RESULTS: A total of 375 articles were analyzed. MAIN
      FINDINGS: 1) The proportion of articles depicting psychiatric disorders together
      with either self- or other-directed aggressive behavior is 31.2%; 2) Homicide was
      most frequently mentioned in the context of psychotic disorders and
      schizophrenia, while affective disorders were most frequently associated with
      both completed suicides and homicides; 3) Eating disorders and anxiety disorders
      were seldom associated with any kind of aggressive behavior, including self-harm;
      4) The vast majority of articles presented mentally ill people as perpetrators,
      and these articles were more often coded as stigmatizing. 5) Articles with
      aggressive behavior mentioned on the cover are roughly as frequent as those with
      aggressive behavior in the later sections of the media (36.7% vs. 30.7%).
      CONCLUSIONS: The results are similar to the findings in countries with longer
      histories of consistent advocacy for improved depiction of mental illness in the
      media. However, we have shown that persons with mental illness are still over
      portrayed as perpetrators of violent crimes, especially homicides.

PMID- 22409959
TI  - Robotic surgical staging for obese patients with endometrial cancer.
AB  - OBJECTIVE: To compare surgical outcomes for robotic vs laparotomy staging in
      obese endometrial cancer patients. STUDY DESIGN: This was a retrospective cohort
      study of patients with body mass index >=30 kg/m(2) staged in a community
      gynecologic oncology practice. Patients undergoing robotic staging were compared
      with historic laparotomy controls. RESULTS: One hundred twenty-nine patients
      underwent robotic staging, compared with 110 laparotomy patients. The robotic
      cohort had fewer abdominal wound complications (13.9% vs 32.7%, P < .001), but
      more vaginal cuff complications (4.7% vs 0%, P = .032). Blood loss was lower in
      the robotic group (P < .001), as was length of stay (P < .001). Surgical times
      were longer in the robotic group (P < .001). There was no difference in terms of
      percentage of patients undergoing pelvic or paraaortic lymph node dissection.
      CONCLUSION: Robotic staging for endometrial cancer is feasible in obese women,
      with fewer abdominal wound complications, but more vaginal cuff complications.

PMID- 22409960
TI  - H1N1 influenza outcome in rheumatic patients under biological therapy.

PMID- 22409961
TI  - Pictet-Spenglerase involved in tetrahydroisoquinoline antibiotic biosynthesis.
AB  - Nonribosomal peptide synthetase (NRPS) is a programmable modular machinery that
      produces a number of biologically active small-molecule peptides. Saframycin A is
      a potent antitumor antibiotic with a unique pentacyclic tetrahydroisoquinoline
      scaffold. We found that the nonribosomal peptide synthetase SfmC catalyzes a
      seven-step transformation of readily synthesized dipeptidyl substrates with long
      acyl chains into a complex saframycin scaffold. Based on a series of enzymatic
      reactions, we proposed a detailed mechanism involving the reduction of various
      peptidyl thioesters by a single R domain followed by iterative C domain-mediated
      Pictet-Spengler reactions. This shows that NRPSs possess a remarkable capability
      to acquire novel function for diversifying structures of peptide natural
      products.

PMID- 22409962
TI  - Canadian Association of Radiologists Radiation Protection Working Group: review
      of radiation units and the use of computed tomography dose indicators in Canada.

PMID- 22409963
TI  - Induction of long-term B-cell depletion in refractory rheumatoid arthritis
      patients preferentially affects autoreactive more than protective humoral
      immunity.
AB  - INTRODUCTION: B-cell depletion has become a common treatment strategy in anti-TNF
      refractory rheumatoid arthritis (RA). Although the exact mechanism of how B-cell
      depletion leads to clinical amelioration in RA remains to be elucidated,
      repetitive treatment with B-cell-depleting agents leading to long-term B-cell
      depletion has been reported to be beneficial. The latter has led to the
      hypothesis that the beneficial effects of B-cell depletion might act through
      their influence on pathogenic autoreactive plasma cells. METHODS: In this study,
      we investigated the effects of a fixed retreatment regimen with anti-CD20 mAbs on
      the humoral (auto)immune system in a cohort of therapy-refractory RA patients.
      RESULTS: Fixed retreatment led to long-term B-cell depletion in peripheral blood,
      bone marrow and, to a lesser extent, synovium. Also, pathologic autoantibody
      secretion (that is, anticitrullinated peptide antibodies (ACPAs)) was more
      profoundly affected by long-term depletion than by physiological protective
      antibody secretion (that is, against measles, mumps and rubella). This was
      further illustrated by a significantly shorter estimated life span of ACPA-IgG
      secretion compared to total IgG secretion as well as protective antibody
      secretion. CONCLUSION: By studying plasma cell function during an extensive 2
      year period of B-cell depletion, autoantibody secretion was significantly shorter
      lived than physiologically protective antibody secretion. This suggests that the
      longevity of autoreactive plasma cells is different from protective long-lived
      plasma cells and might indicate a therapeutic window for therapies that target
      plasma cells.

PMID- 22409964
TI  - Assessing the impact of diabetes-related comorbidities and care on the
      hospitalization costs for patients with diabetes mellitus in Japan.
AB  - OBJECTIVE: Because diabetes mellitus (DM) has been highlighted in several
      healthcare sectors, variations in the case mix of DM should be evaluated to
      promote effective disease management. Using a Japanese administrative database
      (2003), we investigated the impact of DM-related comorbidities and of their
      relevant care processes on healthcare costs incurred during hospitalization.
      METHODS: Of 283,771 hospital admissions across 174 acute care hospitals, 27,853
      patients with DM were analyzed. The following variables were analyzed according
      to age (<65 or >=65 years), the presence of comorbidities, demographic
      characteristics, procedure-related complications, insulin use, surgical
      procedures (percutaneous minimally invasive intervention, hemodialysis,
      ventilation, and rehabilitation), length of stay (LOS), and total charge (TC;
      US$1=Y90). Multivariate analyses were applied to investigate the effects of DM
      related complications and care processes associated with DM on TC. RESULTS: The
      mortality and procedure-related complication rates were 2.1% and 2.7%,
      respectively. There were significant differences in the frequencies of
      comorbidities by age category. Among DM-related comorbidities, peripheral
      vascular disease had the greatest impact on increasing the LOS or TC. Minimally
      invasive procedures, hemodialysis, ventilation, and procedure-related
      complications were significant determinants of TC. Hemodialysis and invasive
      surgical procedures were independent predictors of procedure-related
      complications. CONCLUSIONS: DM-related comorbidities and care process
      representative of the DM case mix were responsible for variations in healthcare
      costs during hospitalization.

PMID- 22409965
TI  - Structural analysis of eyespots: dynamics of morphogenic signals that govern
      elemental positions in butterfly wings.
AB  - BACKGROUND: To explain eyespot colour-pattern determination in butterfly wings,
      the induction model has been discussed based on colour-pattern analyses of
      various butterfly eyespots. However, a detailed structural analysis of eyespots
      that can serve as a foundation for future studies is still lacking. In this
      study, fundamental structural rules related to butterfly eyespots are proposed,
      and the induction model is elaborated in terms of the possible dynamics of
      morphogenic signals involved in the development of eyespots and parafocal
      elements (PFEs) based on colour-pattern analysis of the nymphalid butterfly
      Junonia almana. RESULTS: In a well-developed eyespot, the inner black core ring
      is much wider than the outer black ring; this is termed the inside-wide rule. It
      appears that signals are wider near the focus of the eyespot and become narrower
      as they expand. Although fundamental signal dynamics are likely to be based on a
      reaction-diffusion mechanism, they were described well mathematically as a type
      of simple uniformly decelerated motion in which signals associated with the outer
      and inner black rings of eyespots and PFEs are released at different time points,
      durations, intervals, and initial velocities into a two-dimensional field of
      fundamentally uniform or graded resistance; this produces eyespots and PFEs that
      are diverse in size and structure. The inside-wide rule, eyespot distortion,
      structural differences between small and large eyespots, and structural changes
      in eyespots and PFEs in response to physiological treatments were explained well
      using mathematical simulations. Natural colour patterns and previous experimental
      findings that are not easily explained by the conventional gradient model were
      also explained reasonably well by the formal mathematical simulations performed
      in this study. CONCLUSIONS: In a mode free from speculative molecular
      interactions, the present study clarifies fundamental structural rules related to
      butterfly eyespots, delineates a theoretical basis for the induction model, and
      proposes a mathematically simple mode of long-range signalling that may reflect
      developmental mechanisms associated with butterfly eyespots.

PMID- 22409966
TI  - Is local ointment or cauterization more effective in childhood recurrent
      epistaxis.
AB  - OBJECTIVES: To compare the efficacy of nasal antiseptic ointment and silver
      nitrate cautery in the treatment of children with recurrent epistaxis. METHODS:
      In this prospective and randomized study, a hundred children with recurrent
      epistaxis were assigned into two groups. In group 1, patients underwent silver
      nitrate cauterization, in group 2 patients were treated with nasal antiseptic
      ointment (oxytetracycline hydrochloride-polymyxin B sulfate); and both groups
      were followed for 3 months. All of the patients were investigated for allergy
      with skin prick test. RESULTS: The ages of patients were similar in both groups
      (group 1: 9.2+/-2.7; group 2: 8.2+/-2.2; p=0.069). Thirty-eight percent of the
      patients in group 1 and 52% of the patients in group 2 had epistaxis in the three
      months follow-up. The difference between groups was not significant (p=0.159).
      Thirteen (26%) of the patients in group 1 and 12 (24%) of the patients in group 2
      were found to have allergic symptoms and positive prick test. The rate of allergy
      was similar in both groups (p=0.817). CONCLUSION: Nasal antiseptic ointment and
      silver nitrate cauterization were found to have similar outcomes in the treatment
      of recurrent epistaxis.

PMID- 22409967
TI  - Dimeric 3,5-bis(benzylidene)-4-piperidones: a novel cluster of tumour-selective
      cytotoxins possessing multidrug-resistant properties.
AB  - A series of bis[3,5-bis(benzylidene)-4-oxo-1-piperidinyl]amides 1 display potent
      cytotoxic properties towards a wide range of tumours. A number of the CC(50) and
      IC(50) values are in the range of 10(-8) M. Specifically, these compounds have
      the following important properties. First, greater toxicity was demonstrated
      towards certain tumours than various non-malignant cells. Second, various
      compounds in series 1 are toxic to a number of human colon cancer and leukaemic
      cells. Third, these compounds reverse P-gp mediated multidrug resistance. Various
      prototypic molecules such as 1a,b and 1i were identified as lead molecules for
      further studies. A representative lead molecule 1b induces apoptosis via
      internucleosomal DNA fragmentation and PARP cleavage in HSC-2 and HL-60 cells
      while flow cytometry revealed that this compound blocked the G2/M and S-phases in
      the cell cycle of human colon cancer HCT-116 cells.

PMID- 22409968
TI  - Synthesis of new troglitazone derivatives: anti-proliferative activity in breast
      cancer cell lines and preliminary toxicological study.
AB  - Breast cancer is the most prevalent cancer in women. The development of
      resistances to therapeutic agents and the absence of targeted therapy for triple
      negative breast cancer motivate the search for alternative treatments. With this
      aim in mind, we synthesised new derivatives of troglitazone, a compound which was
      formerly used as an anti-diabetic agent and which exhibits anti-proliferative
      activity on various cancer cell lines. Among the compounds prepared, some
      displayed micromolar activity against hormone-dependent and hormone-independent
      breast cancer cells. Furthermore, the influence of the compounds on the viability
      of primary cultures of human hepatocytes was evaluated. This enabled us to obtain
      for the first time interesting structure-toxicity relationships in this family of
      compounds, resulting in 6b and 8b, which show good anti-proliferative activities
      and poor toxicity towards hepatocytes, compared to troglitazone.

PMID- 22409969
TI  - Exhaled nitric oxide decreases after positive food-allergen challenge.
AB  - BACKGROUND: Exhaled nitric oxide (FeNO) is a well described marker of airway
      inflammation in asthma and is also known to increase after chronic exposure to
      inhaled allergens. It is not known whether monitoring FeNO could be useful during
      food challenges to detect early or subclinical reactions. METHODS: Forty children
      aged 3 to 16 years undergoing an allergen-food challenge at two centres were
      prospectively recruited for this study. FeNO was assessed before and repeatedly
      after the food-challenge. RESULTS: Data were obtained from a total of 53
      challenges (16 positive, 37 negative) and were compared between the two groups.
      Half of the patients with a positive food challenge exhibited clinical upper
      respiratory symptoms. The FeNO significantly decreased in 7 of 16 patients with a
      positive challenge test within 60 to 90 minutes after the first symptoms of an
      allergic reaction. CONCLUSION: Our results show a significant decrease in FeNO
      after a positive food challenge suggesting involvement of the lower airways
      despite absence of clinical and functional changes of lower airways. Prospective
      blinded studies are needed to confirm these results.

PMID- 22409970
TI  - Gangliosides and chondroitin sulfate desensitize and internalize B2 bradykinin
      receptors.
AB  - Prolonged or repeated agonist activation of G-protein-coupled receptors (GPCRs)
      initiates their desensitization and internalization, rendering them unresponsive
      to agonist activation. We analyzed how gangliosides and chondroitin sulfate
      affect B2 bradykinin (BK) receptors (B2Rs). Gangliosides and chondroitin sulfate
      did not stimulate intracellular Ca(2+) release from B2R-expressing CHO-K1 cells,
      but repeated exposure desensitized B2Rs to BK stimulation. Microscopic
      observation of DsRed-fused B2Rs revealed that several gangliosides and
      chondroitin sulfate C (CSC) effectively internalized B2Rs. Ganglioside-CSC
      treatment of B2R mutant-expressing cells failed to desensitize and internalize
      the mutant receptors. As this mutant lacks the first extracellular domain and
      cannot activate GPCR kinase (GRK), gangliosides and CSC likely initiate B2R
      desensitization and endocytosis through GRK-mediated B2R phosphorylation.

PMID- 22409971
TI  - Gold nanoparticles as high-resolution X-ray imaging contrast agents for the
      analysis of tumor-related micro-vasculature.
AB  - BACKGROUND: Angiogenesis is widely investigated in conjunction with cancer
      development, in particular because of the possibility of early stage detection
      and of new therapeutic strategies. However, such studies are negatively affected
      by the limitations of imaging techniques in the detection of microscopic blood
      vessels (diameter 3-5 MUm) grown under angiogenic stress. We report that
      synchrotron-based X-ray imaging techniques with very high spatial resolution can
      overcome this obstacle, provided that suitable contrast agents are used. RESULTS:
      We tested different contrast agents based on gold nanoparticles (AuNPs) for the
      detection of cancer-related angiogenesis by synchrotron microradiology,
      microtomography and high resolution X-ray microscopy. Among them only bare-AuNPs
      in conjunction with heparin injection provided sufficient contrast to allow in
      vivo detection of small capillary species (the smallest measured lumen diameters
      were 3-5 MUm). The detected vessel density was 3-7 times higher than with other
      nanoparticles. We also found that bare-AuNPs with heparin allows detecting
      symptoms of local extravascular nanoparticle diffusion in tumor areas where
      capillary leakage appeared. CONCLUSIONS: Although high-Z AuNPs are natural
      candidates as radiology contrast agents, their success is not guaranteed, in
      particular when targeting very small blood vessels in tumor-related angiography.
      We found that AuNPs injected with heparin produced the contrast level needed to
      reveal--for the first time by X-ray imaging--tumor microvessels with 3-5 MUm
      diameter as well as extravascular diffusion due to basal membrane defenestration.
      These results open the interesting possibility of functional imaging of the tumor
      microvasculature, of its development and organization, as well as of the effects
      of anti-angiogenic drugs.

PMID- 22409972
TI  - Unilateral lesion of dorsal hippocampus in adult rats impairs contralateral long
      term potentiation in vivo and spatial memory in the early postoperative phase.
AB  - It is well documented that bilateral hippocampal lesions or unilateral
      hippocampal lesion at birth causes impairment of contralateral LTP and long-term
      memory. However, effects of unilateral hippocampal lesion in adults on
      contralateral in vivo LTP and memory are not clear. We here examined the
      influence of unilateral electrolytic dorsal hippocampal lesion in adult rats on
      contralateral LTP in vivo and spatial memory during different postoperative
      phases. We found that acute unilateral hippocampal lesion had no effect on
      contralateral LTP. However, contralateral LTP was impaired at 1 week after
      lesion, and was restored to the control level at postoperative week 4. Similarly,
      spatial memory was also impaired at postoperative week 1, and was restored at
      postoperative week 4. In addition, the rats at postoperative week 1 showed
      stronger spatial exploratory behavior in a novel open-field environment. The sham
      operation had no effects on contralateral LTP, spatial memory and exploration at
      either postoperative week 1 or week 4. These results suggest that unilateral
      dorsal hippocampal lesion in adult rats causes transient contralateral LTP
      impairment and spatial memory deficit.

PMID- 22409973
TI  - Tactile stimulation during development alters behaviour and neuroanatomical
      organization of normal rats.
AB  - The purpose of this study was to examine the anatomical and behavioural sequelae
      in the normal brain associated with tactile stimulation treatment during
      development. Using a split litter design, male and female rats were randomly
      assigned to either the tactile stimulation group (tactile stimulation for 15 min,
      three times/day, from postnatal day 3 to 21), or the no-tactile stimulation
      group. In adulthood, the rats were tested on the Whishaw tray reaching task,
      activity box, novel object recognition, and elevated plus maze. Following
      behavioural testing, rats were sacrificed for Golgi-Cox analysis. Dendritic
      length, dendritic branching, and spine density were analyzed in two areas of the
      prefrontal cortex (mPFC and OFC) and spine density in the amygdala. Tactile
      stimulation significantly altered rat behaviour on the novel object recognition
      task and Whishaw tray reaching task, but failed to have an effect on behaviour in
      the elevated plus maze or activity box. Importantly, tactile stimulation
      dramatically altered dendritic morphology in the prefrontal cortex and amygdala
      of both male and female rats. Tactile stimulation significantly increased
      dendritic branching, dendritic length, and spine density in all brain regions
      examined. These findings demonstrate that similar to early adversity, positive
      experiences early in development can dramatically alter neuroplasticity.

PMID- 22409974
TI  - Prefrontal dopamine release and sensory-specific satiety altered in rats with
      neonatal ventral hippocampal lesions.
AB  - Rats with a neonatal ventral hippocampal lesion (NVHL) have been used to model
      certain features of schizophrenia because they display dopaminergic activity and
      behavioral alterations consistent with a dysfunctional prefrontal cortex after
      puberty. Microdialysis studies in normal rats demonstrated increased prefrontal
      dopamine release during the incentive phase of behavior in an experimental
      situation specifically designed to evidence this behavioral aspect: the so called
      "sensory-specific satiety" procedure. Our hypothesis is that if dopaminergic
      activity in the prefrontal cortex of NVHL rats differs from sham lesioned rats,
      the responsiveness to the aforementioned experimental situation should also be
      different. Extracellular medial prefrontal dopamine outflow increased in hungry
      control rats when they had access to food and decreased across satiety. It
      increased again when a new food was presented, even when the rats were satiated.
      NVHL rats also had increased dopamine prefrontal outflow in these conditions, but
      it remained high after the end of the consumption period. The food consumption
      behavior declined less rapidly and the reinstatement of food consumption, usually
      produced by new food, did not occur in NVHL rats, provided the lesions were
      large. These data were discussed in relation to several theoretical backgrounds
      developed about the incentive aspect of behavior and for understanding the
      pathophysiology of schizophrenia.

PMID- 22409975
TI  - Age-related changes in visual acuity, learning and memory in the APPswe/PS1dE9
      mouse model of Alzheimer's disease.
AB  - Mouse models of Alzheimer's disease (AD) are often tested for learning and memory
      deficits using visuo-spatial tasks such as the Morris water maze. Performance on
      these tasks is dependent on vision and the APPswe/PS1dE9 mouse model has amyloid
      beta plaques in their retinas which might influence their performance in these
      tasks. In a visual learning task, old (20-26 months) transgenic mice and their
      wildtype littermates of both sexes had poorer visual ability than young (5-8
      months) mice and old transgenic mice had poorer visual acuity than old wildtype
      mice. Old transgenic mice also had deficits in visuo-spatial learning and memory
      on the Morris water maze. The transgenic mice had no deficits in the conditioned
      odour preference or conditioned taste aversion memory tests at any age. These
      results indicate that the old APPswe/PS1dE9 mice and their wildtype littermates
      both have a deficit in their visual ability and that visually dependent measures
      alone should not be used to assess learning and memory in this strain.

PMID- 22409976
TI  - Prenatal exposure to chronic mild stress increases corticosterone levels in the
      amniotic fluid and induces cognitive deficits in female offspring, improved by
      treatment with the antidepressant drug amitriptyline.
AB  - Prenatal stress and associated in utero exposure to elevated levels of stress
      hormones can adversely affect the development of the central nervous system,
      thereby increasing the risk of mental illnesses in later life. Here, we examined
      the impact of prenatal exposure to chronic mild stress (CMS) on locomotion,
      anxiety-related behaviour, cognition and hippocampal serotonergic
      neurotransmission in juvenile and adult B6D2F2 mice, and whether antidepressant
      treatment in adulthood could reverse the observed behavioural disturbances.
      Pregnant B6D2F1 female mice were either subjected to CMS or left undisturbed
      until parturition. Three-week and 7-week-old male and female offspring were
      assessed in the open-field, novel object recognition and contextual fear
      conditioning tests. Hippocampal levels of serotonin and its major metabolite were
      then quantified using high-performance liquid chromatography. Some prenatally
      stressed adult females were treated with amitriptyline (20mg/kg/day in drinking
      water) for 10 days, from the day prior to onset of behavioural testing. In a
      separate experiment, amniotic fluid was collected from stressed and non-stressed
      dams on gestational (G) days 13 and 18 to quantify levels of corticosterone. We
      found that prenatal CMS specifically impaired learning and memory performance in
      adult females. Amitriptyline elevated hippocampal serotonin levels and attenuated
      these cognitive deficits. Corticosterone levels in the amniotic fluid were
      increased by CMS on G13 but by G18, the levels in non-stressed dams reached those
      of stressed dams. These results suggest that female mice are particularly
      vulnerable to the adverse developmental effects of prenatal stress which can be
      improved by appropriate treatment strategies including antidepressants.

PMID- 22409977
TI  - The effect of spatial heterogenity on the aggregation of ticks on white-footed
      mice.
AB  - Parasites are often aggregated on a minority of the individuals in their host
      populations. Although host characteristics are commonly presumed to explain
      parasite aggregation on hosts, spatio-temporal aggregation of parasites during
      their host-seeking stages may have a dominant effect on the aggregation on hosts.
      We aimed to quantify, using mixed models, repeatability and autocorrelation
      analyses, the degree to which the aggregation of blacklegged ticks (Ixodes
      scapularis) on white-footed mice (Peromyscus leucopus) is influenced by spatio
      temporal distributions of the host-seeking ticks and by heterogeneity among mice.
      Host-seeking ticks were spatially aggregated at both the larval and nymphal life
      stages. However, this spatial aggregation accounted for little of the variation
      in larval and nymphal burdens observed on mice (3% and 0%, respectively).
      Conversely, mouse identity accounted for a substantial proportion of the variance
      in tick burdens. Mouse identity was a significant explanatory factor as the
      majority of ticks parasitized a consistent set of mice throughout the activity
      seasons. Of the characteristics associated with mouse identity investigated, only
      gender affected larval burdens, and body mass and home range sizes in males were
      correlated with nymphal burdens. These analyses suggest that aggregation of ticks
      on a minority of mice does not result from the distribution of host-seeking ticks
      but from characteristics of the hosts.

PMID- 22409978
TI  - The gap in injury mortality rates between urban and rural residents of Hubei
      Province, China.
AB  - BACKGROUND: Injury is a growing public health concern in China. Injury death
      rates are often higher in rural areas than in urban areas in general. The
      objective of this study is to compare the injury mortality rates in urban and
      rural residents in Hubei Province in central China by age, sex and mechanism of
      injury. METHODS: Using data from the Disease Surveillance Points (DSP) system
      maintained by the Hubei Province Centers for Disease Control and Prevention (CDC)
      from 2006 to 2008, injury deaths were classified according to the International
      Classification of Disease-10th Revision (ICD-10). Crude and age-adjusted annual
      mortality rates were calculated for rural and urban residents of Hubei Province.
      RESULTS: The crude and age-adjusted injury death rates were significantly higher
      for rural residents than for urban residents (crude rate ratio 1.9, 95%
      confidence interval 1.8-2.0; adjusted rate ratio 2.4, 95% confidence interval 2.3
      2.4). The age-adjusted injury death rate for males was 81.6/100,000 in rural
      areas compared with 37.0/100,000 in urban areas; for females, the respective
      rates were 57.9/100,000 and 22.4/100,000. Death rates for suicide (32.4 per
      100,000 vs 3.9 per 100,000), traffic-related injuries (15.8 per 100,000 vs 9.5
      per 100,000), drowning (6.9 per 100,000 vs 2.3 per 100,000) and crushing injuries
      (2.0 per 100,000 vs 0.7 per 100,000) were significantly higher in rural areas.
      Overall injury death rates were much higher in persons over 65 years, with
      significantly higher rates in rural residents compared with urban residents for
      suicide (279.8 per 100,000 vs 10.7 per 100,000), traffic-related injuries, and
      drownings in this age group. Death rates for falls, poisoning, and suffocation
      were similar in the two geographic groups. CONCLUSIONS: Rates of suicide, traffic
      related injury deaths and drownings are demonstrably higher in rural compared
      with urban locations and should be targeted for injury prevention activity. There
      is a need for injury prevention policies targeted at elderly residents,
      especially with regard to suicide prevention in rural areas in Central China.

PMID- 22409979
TI  - Sequential solid-state and submerged cultivation of Aspergillus niger on
      sugarcane bagasse for the production of cellulase.
AB  - Sequential solid-state and submerged cultivation with sugarcane bagasse as
      substrate for cellulase production by Aspergillus niger A12 was assessed by
      measuring endoglucanase activity. An unconventional pre-culture with an initial
      fungal growth phase under solid-state cultivation was followed by a transition to
      submerged fermentation by adding the liquid culture medium to the mycelium grown
      on solid substrate. For comparison, control experiments were conducted using
      conventional submerged cultivation. The cultures were carried out in shake flasks
      and in a 5-L bubble column bioreactor. An endoglucanase productivity of 57 +/- 13
      IU/L/h was achieved in bubble column cultivations prepared using the new method,
      representing an approximately 3-fold improvement compared to conventional
      submerged fermentation. Therefore, the methodology proposed here of a sequential
      fermentation process offers a promising alternative for cellulase production.

PMID- 22409980
TI  - Co-digestion of polylactide and kitchen garbage in hyperthermophilic and
      thermophilic continuous anaerobic process.
AB  - Two series of two-phase anaerobic systems, consisting of a hyperthermophilic (80
      degrees C) reactor and a thermophilic (55 degrees C) reactor, fed with a mixture
      of kitchen garbage (KG) and polylactide (PLA), was compared with a single-phase
      thermophilic reactor for the overall performance. The result indicated that
      ammonia addition under hyperthermophilic condition promoted the transformation of
      PLA particles to lactic acid. The systems with hyperthermophilic treatment had
      advantages on PLA transformation and methane conversion ratio to the control
      system. Under the organic loading rate (OLR) of 10.3 g COD/(L day), the PLA
      transformation ratios of the two-phase systems were 82.0% and 85.2%,
      respectively, higher than that of the control system (63.5%). The methane
      conversion ratios of the two-phase systems were 82.9% and 80.8%, respectively,
      higher than 70.1% of the control system. The microbial community analysis
      indicated that hyperthermophilic treatment is easily installed to traditional
      thermophilic anaerobic digestion plants without inoculation of special bacteria.

PMID- 22409981
TI  - The sorption of pentachlorophenol by aged sediment supplemented with black carbon
      produced from rice straw and fly ash.
AB  - Black carbon (BC) is a potential material for controlling hydrophobic organic
      contaminants in sediment because it has a high sorption capacity. In the present
      study, the sorption of pentachlorophenol (PCP) onto sediments supplemented with
      rice straw biochar (RC) and fly ash (FC) aged for different times and at
      temperatures were investigated. The sorption of PCP increased with increasing
      amounts of BC and decreased with aging time and storage temperature of the BC
      supplemented sediments. The sorption of PCP onto RC-supplemented sediments was
      higher than those supplemented with FC regardless of whether or not BCs were aged
      in sediments. For aged sediments containing 2% BCs, the sorption capacity was
      9.15- and 2.87-fold higher than that of FC when supplemented with RC aged at 25
      and 45 degrees C, respectively. Therefore, biochar is better than fly ash for
      controlling organic pollutants even when the RC was present in sediment for a
      long time.

PMID- 22409982
TI  - Elimination of carbamazepine in a non-sterile fungal bioreactor.
AB  - A properly configured bioreactor is in need to transfer the fungal biodegradation
      of recalcitrant pollutants into real applications. In this study, a novel plate
      bioreactor was designed to eliminate carbamazepine (CBZ), a widely concerned
      pharmaceutical, with the white rot fungus Phanerochaete chrysosporium grown on
      polyether foam under non-sterile conditions. The bioreactor was operated in both
      sequence batch and continuous modes. It was found that the sufficient supply with
      nutrients is crucial for an effective elimination of CBZ. Given the conditions, a
      high elimination of CBZ (60-80%) was achieved. The effective elimination was
      stable in a continuous operation for a long term (around 100 days). The high
      elimination of CBZ could also be achieved under real conditions with the effluent
      from a municipal wastewater treatment plant.

PMID- 22409983
TI  - Construction and characterization of chimeric cellulases with enhanced catalytic
      activity towards insoluble cellulosic substrates.
AB  - The chimeric proteins viz. CBM3-Cel9A, CBM4-Cel9A and CBM30-Cel9A, are
      constructed by fusion of family 3, 4, and 30 cellulose binding modules (CBMs) to
      N-terminus of family 9 endoglucanase (Cel9A) from Alicyclobacillus
      acidocaldrious. The chimeric enzymes were successfully expressed in Escherichia
      coli and purified to homogeneity. The chimeric enzymes showed significant
      increase in Avicel (8-12 folds) and filter paper (7-10 folds) degradation
      activities compared to Cel9A endoglucanase. Computational protein modeling and
      simulation on the chimeric enzymes were applied to analyze the fused CBMs effect
      on the increased insoluble cellulosic substrates degradation activity. Thin layer
      chromatography analysis of the enzymatic hydrolysis products and distribution of
      reducing sugars between soluble and insoluble fractions indicated processive
      cleavage of insoluble cellulosic substrates by the chimeras. The fused CBMs
      played a critical accessory role for the Cel9A catalytic domain and changed its
      character to facilitate the processive cleavage of insoluble cellulosic
      substrates.

PMID- 22409984
TI  - Oral food challenges in a practice setting apart from hospitals and academic
      centers.

PMID- 22409985
TI  - Reply.

PMID- 22409986
TI  - Does "autoreactivity" play a role in atopic dermatitis?
AB  - The role of autoimmunity in atopic dermatitis (AD) is unclear. We sought to
      critically examine the occurrence, correlation with severity, and possible
      causative role of autoreactivity in patients with AD. Our systematic review of
      studies identified from MEDLINE included 31 experiments that described
      autoreactivity in patients with AD. We defined autoreactivity as in vitro or in
      vivo evidence of immune response to autologous human, generic human, or
      recombinant human proteins or other tissue/cellular components. Autoreactivity
      prevalence in patients with AD ranged from 23% to 91% in 14 studies involving
      2644 participants, although it did not appear to vary with age, sex, or disease
      duration. In contrast to studies of AD, IgE autoreactivity was not found in
      healthy subjects or in those with allergic rhinoconjunctivitis, psoriasis,
      systemic lupus erythematosus, or other inflammatory diseases (8 studies of 816
      participants). Two reports found a positive correlation between autoreactivity
      and AD severity. We suggest that autoreactivity might be playing a causative role
      in AD based on the magnitude and specificity of the associations found; plausible
      mechanisms through IgE autoantibodies, IgG autoantibodies, and T(H)1
      autoreactivity; and experimental elicitation of eczematous lesions after
      provocation. Whether autoantibodies contribute to AD chronicity now needs to be
      examined in longitudinal studies.

PMID- 22409987
TI  - CRACM/Orai ion channel expression and function in human lung mast cells.
AB  - BACKGROUND: Influx of extracellular Ca(2+) into human lung mast cells (HLMCs) is
      essential for the FcepsilonRI-dependent release of preformed granule-derived
      mediators and newly synthesized autacoids and cytokines. However, the identity of
      the ion channels underlying this Ca(2+) influx is unknown. The recently
      discovered members of the CRACM/Orai ion channel family that carries the Ca(2+)
      release-activated Ca(2+) current are candidates. OBJECTIVES: To investigate the
      expression and function of CRACM channels in HLMCs. METHODS: CRACM mRNA, protein,
      and functional expression were examined in purified HLMCs and isolated human
      bronchus. RESULTS: CRACM1, -2, and -3 mRNA transcripts and CRACM1 and -2 proteins
      were detectable in HLMCs. A CRACM-like current was detected following FcepsilonRI
      dependent HLMC activation and also in HLMCs dialyzed with 30 MUM inositol
      triphosphate. The Ca(2+)-selective current obtained under both conditions was
      blocked by 10 MUM La(3+) and Gd(3+), known blockers of CRACM channels, and 2
      distinct and specific CRACM-channel blockers-GSK-7975A and Synta-66. Both
      blockers reduced FcepsilonRI-dependent Ca(2+) influx, and 3 MUM GSK-7975A and
      Synta-66 reduced the release of histamine, leukotriene C(4), and cytokines (IL-5/
      8/-13 and TNFalpha) by up to 50%. Synta-66 also inhibited allergen-dependent
      bronchial smooth muscle contraction in ex vivo tissue. CONCLUSIONS: The presence
      of CRACM channels, a CRACM-like current, and functional inhibition of HLMC Ca(2+)
      influx, mediator release, and allergen-induced bronchial smooth muscle
      contraction by CRACM-channel blockers supports a role for CRACM channels in
      FcepsilonRI-dependent HLMC secretion. CRACM channels are therefore a potential
      therapeutic target in the treatment of asthma and related allergic diseases.

PMID- 22409988
TI  - Altered stratum corneum barrier and enhanced percutaneous immune responses in
      filaggrin-null mice.
AB  - BACKGROUND: Loss-of-function mutations in filaggrin are major predisposing
      factors for atopic dermatitis. Although various reports suggest a critical role
      for filaggrin in stratum corneum (SC) barrier formation, the lack of filaggrin
      null (Flg(-/-)) mice has hampered detailed in vivo analysis of filaggrin's
      functions. OBJECTIVE: We sought to generate Flg(-/-) mice and to assess the
      effect of filaggrin loss on SC barrier function and percutaneous immune
      responses. METHODS: We generated Flg(-/-) mice using gene targeting and assessed
      the morphology, hydration, mechanical strength, and antigen permeability of their
      SC. Percutaneous immune responses were evaluated through irritant- and hapten
      induced contact hypersensitivity studies and by measuring humoral responses to
      epicutaneous sensitization with protein antigen. RESULTS: Newborn Flg(-/-) mice
      exhibited dry scaly skin. Despite marked decreases in natural moisturizing factor
      levels, which are filaggrin degradation products, SC hydration and transepidermal
      water loss were normal. Microscopic analyses suggested premature shedding of SC
      layers, and indeed, increased desquamation under mechanical stress was
      demonstrated. Loss of keratin patterns, which are critical for corneocyte
      stabilization, is likely attributable to fragility in the Flg(-/-) SC. Antigens
      penetrated the Flg(-/-) SC more efficiently, leading to enhanced responses in
      hapten-induced contact hypersensitivity and higher serum levels of anti-ovalbumin
      IgG(1) and IgE. CONCLUSION: Complete filaggrin deficiency led to altered barrier
      integrity and enhanced sensitization, which are important factors in early-phase
      atopic dermatitis. Flg(-/-) mice should provide a valuable tool to further
      explore additional factors the dysfunction of which leads to uncontrolled
      inflammation in patients with atopic diseases.

PMID- 22409989
TI  - Pulmonary alveolar proteinosis in patients with adenosine deaminase deficiency.
AB  - BACKGROUND: Inherited defects in the function of adenosine deaminase (ADA) cause
      severe combined immunodeficiency (SCID) and affect many other cells and tissues.
      OBJECTIVES: We sought to characterize the frequency and features of pulmonary
      alveolar proteinosis (PAP) in patients with ADA deficiency. METHODS: Clinical and
      laboratory features of all patients with SCID caused by ADA deficiency in a
      single center were analyzed. Bronchoalveolar lavage (BAL) fluid and lung biopsy
      specimens were stained with hematoxylin and eosin and periodic acid-Schiff,
      visualized by means of electron microscopy, and studied for associated
      infections. As a control group, BAL fluid and biopsy specimens from 22 patients
      with SCID caused by other genetic abnormalities were similarly assessed. RESULTS:
      Among 16 consecutive patients with ADA deficiency, 7 had BAL fluid containing
      periodic acid-Schiff-positive surfactant-like material with macrophages engulfing
      degenerating lamellar bodies and/or lung biopsy specimens with alveolar spaces
      filled with homogeneous granular eosinophilic material and large macrophages. The
      lung pathology was typical of PAP. Identification of various pathogens coincided
      with PAP in 3 of these patients. We have diagnosed PAP among patients with ADA
      deficiency more commonly in the last 10 years than previously (P= .05), likely
      reflecting increased awareness of this condition. There were no significant
      differences in the clinical or immunologic characteristics between patients with
      ADA deficiency with or without PAP. Similar findings of PAP were not found among
      patients with SCID caused by other genetic abnormalities (P= .001). ADA coupled
      to polyethylene glycol or allogeneic hematopoietic stem cell transplantation
      rapidly corrected this pulmonary complication. PAP seems to have contributed to
      the death of only 1 patient with ADA deficiency. CONCLUSIONS: ADA deficiency
      predisposes to the development of PAP, which could be reversed after enzyme
      replacement or transplantation.

PMID- 22409991
TI  - Mental health following traumatic physical injury: an integrative literature
      review.
AB  - AIM: To investigate the state of knowledge on the relationship between physical
      trauma and mental health in patients admitted to hospital with traumatic physical
      injury. BACKGROUND: Adults who sustain traumatic physical injury can experience a
      range of mental health problems related to the injury and subsequent changes in
      physical health and function. However early screening and identification of
      mental health problems after traumatic physical injury is inconsistent and not
      routine during the hospital admission process for the physically injured patient.
      METHODS: Integrative review methods were used. Data were sourced for the period
      1995-2010 from EMBASE, CINAHL, MEDLINE and PsycINFO and hand searching of key
      references. Abstracts were screened by 3 researchers against inclusion/exclusion
      criteria. Forty-one papers met the inclusion criteria. Data were retrieved,
      appraised for quality, analysed, and synthesised into 5 main categories. RESULTS:
      Forty-one primary research papers on the relationship between mental health and
      traumatic physical injury were reviewed. Studies showed that post-traumatic
      stress disorder, depression and anxiety were frequent sequelae associated with
      traumatic physical injury. However, these conditions were poorly identified and
      treated in the acute hospital phase despite their effect on physical health.
      CONCLUSION: There is limited understanding of the experience of traumatic
      physical injury, particularly in relation to mental health. Greater translation
      of research findings to practice is needed in order to promote routine screening,
      early identification and referral to treatment for mental health problems in this
      patient group.

PMID- 22409990
TI  - An ex vivo model of severe asthma using reconstituted human bronchial epithelium.
AB  - BACKGROUND: Structural changes to the airways are features of severe asthma. The
      bronchial epithelium facilitates this remodeling process. Learning about the
      changes that develop in the airway epithelium could improve our understanding of
      asthma pathogenesis and lead to new therapeutic approaches. OBJECTIVE: We sought
      to determine the feasibility and relevance of air-liquid interface cultures of
      bronchial epithelium derived from endobronchial biopsy specimens of patients with
      different severities of asthma for studying the airway epithelium. METHODS: Human
      bronchial epithelial cells derived from endobronchial biopsy specimens of
      patients with mild and severe asthma were maintained in culture for 21 days in an
      air-liquid interface to reproduce a fully differentiated airway epithelium.
      Initially, features of remodeling that included epithelial and subepithelial
      layers, as well as mucus production, were assessed in paraffin-embedded
      endobronchial biopsy specimens to evaluate morphologic characteristics of
      asthmatic patients' epithelia. Ex vivo differentiated epithelia were then
      analyzed for morphology and function based on ultrastructural analysis, IL-8
      release, lipoxin A(4) generation, mucin production, and lipoxygenase gene
      expression. RESULTS: Morphologic and inflammatory imbalances initially observed
      in endobronchial biopsy specimens obtained from patients with severe or mild
      asthma persisted in the air-liquid interface reconstituted epithelium throughout
      the differentiation process to 21 days. Epithelium from patients with severe
      asthma produced greater levels of mucin, released more IL-8, and produced lower
      levels of lipoxin A(4) than that from patients with mild asthma. Expression of 15
      lipoxygenase 2 was increased in epithelium from patients with severe asthma,
      whereas expression levels of MUC5AC, MUC5B, 5-lipoxygenase, and 15-lipoxygeanse 1
      were similar to those of patients with mild asthma. CONCLUSION: Ex vivo cultures
      of fully differentiated bronchial epithelium from endobronchial biopsy specimens
      maintain inherent phenotypic differences specifically related to the severity of
      asthma.

PMID- 22409992
TI  - Functional outcome of nerve transfers for traumatic global brachial plexus
      avulsion.
AB  - BACKGROUND: The treatment of global brachial plexus avulsion is a demanding field
      of hand and upper extremity surgery. The recent development of functional and
      quality-of-life (QOL) assessment tools has improved quantifying these functional
      outcomes after surgery. OBJECTIVE: We sought to combine Medical Research Council
      (MRC) grading with the Disability of the Arm, Shoulder, and Hand (DASH)
      questionnaires and Numerical Rating Scale (NRS) for pain to evaluate the
      functional outcome of patients who suffered complete brachial plexus avulsion
      before and after nerve transfers. METHODS: The author carried out a retrospective
      review of 37 patients with global avulsion of the brachial plexus between 2000
      and 2007. All of them underwent nerve transfers in Hua Shan Hospital in Shanghai.
      They were followed up for over 3 years for physical examination and responding to
      the questionnaires of DASH, NRS, as well as the satisfaction with the surgery.
      RESULTS: The mean time to surgery was less than 6 months and the mean follow-up
      period was 4.59 years (range: 3-9 years). The effective motor recovery rate was
      54%, 86%, 46% and 43%, respectively, in supraspinatus, biceps, triceps and finger
      flexor. Patients who underwent nerve transfers scored consistently better on the
      DASH score and NRS score than those before surgery. There was also a significant
      correlation between the change in NRS scores and patient satisfaction.
      CONCLUSION: This study validated the effect of nerve transfers for global
      brachial plexus avulsions from objective MRC grading combining with patients'
      self-assessments. Neurolysis after neurotisations correlated positively with
      functional outcomes.

PMID- 22409993
TI  - A modified laparoscopic sleeve gastrectomy for the treatment of diabetes mellitus
      type 2 and metabolic syndrome in obesity.
AB  - BACKGROUND: Ghrelin is a gastrointestinal peptide hormone (a 28-amino acid
      peptide) produced primarily by X/A cells in the oxyntic glands of the stomach
      fundus and cells lining the duodenum cavern. It suppresses insulin secretion and
      action and commands a significant role in regulating food intake. The aim of the
      present study was to show that modified laparoscopic sleeve gastrectomy (MLSG),
      in which a significant part of the gastric fundus and body of the stomach is
      removed up to 1 inch from the pylorus vein, may contribute to decreasing
      circulating ghrelin levels. METHODS: A study population consisting of 150
      individuals was monitored after undergoing a MLSG, with individuals chosen based
      on a documented history of diabetes mellitus type 2 and metabolic syndrome,
      clinical results determining a body mass index (BMI) of 35 to 60 kg/m(2), peptide
      C level greater than 1, negative anti-glutamic acid decarboxylase, negative anti
      insulin, and confirmed stability of drug/insulin treatment and glycosylated
      hemoglobin greater than 6.5% for at least 24 and 3 months, respectively, before
      enrollment. RESULTS: Twenty-four months after surgery, 150 patients (86.6%)
      presented with normal glycemic levels between 77 and 99 mg/dL. All patients
      improved average serum insulin levels by 9 mU/L and average glycosylated
      hemoglobin levels by 5.1% (normal range, 4%-6%). All patients tested negative for
      Helicobacter pylori and stopped using insulin, with 3 patients prescribed twice
      daily use of an oral hypoglycemiant. In 14% of cases, patients experienced
      partial hair loss with low serum zinc levels and were prescribed oral zinc
      reposition and topical hair stimulants. The average weight loss recorded was
      44.6% for patients with a BMI less than 45 kg/m(2) and 58% for patients with a
      BMI greater than 50 kg/m(2). CONCLUSIONS: The MLSG is a safe procedure with a low
      morbidity rate (2.7%) (4 cases of fistula and 2 of bleeding) and no surgical
      mortality in this study. This surgery can promote control of diabetes mellitus
      type 2 and aid the treatment of exogenous overweight and morbidly obese
      individuals. The results of this study show that only through resection of the
      ghrelin-producing gastric area can most obesity cases and diabetes type II
      conditions be reverted to nonobese and controlled diabetes.

PMID- 22409995
TI  - Osteoarthritis of the zygapophysial joints: efficacy of percutaneous
      radiofrequency neurotomy in the treatment of lumbar facet joint syndrome.

PMID- 22409994
TI  - Drug resistance: still a daunting challenge to the successful treatment of AML.
AB  - Resistance to chemotherapy remains a challenging issue for patients and their
      physicians. P-glycoprotein (Pgp, MDR1, ABCB1), as well as a family of
      structurally and functionally related proteins, are plasma membrane transporters
      able to efflux a variety of substrates from the cell cytoplasm, including
      chemotherapeutic agents. The discovery of ABCB1 made available a potential target
      for pharmacologic down-regulation of efflux-mediated chemotherapy resistance. In
      patients with acute myeloid leukemia (AML), a neoplasm characterized by
      proliferation of poorly differentiated myeloid progenitor cells, leukemic cells
      often express ABCB1 at high levels, which may lead to the development of
      resistance to chemotherapy. Thus, AML seemed to be a likely cancer for which the
      addition of drug efflux inhibitors to the chemotherapeutic regimen would improve
      outcomes in patients. Despite this rational hypothesis, the majority of clinical
      trials evaluating this strategy have failed to reach a positive endpoint, most
      recently the Eastern Cooperative Oncology Group E3999 trial. Here we review data
      suggesting the importance of ABCB1 in AML, address the failure of clinical trials
      to support a therapeutic strategy aimed at modulating ABCB1-mediated resistance,
      and consider the type of research that should be conducted in this field going
      forward.

PMID- 22409996
TI  - Characterization of synovial angiogenesis in osteoarthritis patients and its
      modulation by chondroitin sulfate.
AB  - INTRODUCTION: This work aimed at comparing the production of inflammatory and pro
      and anti-angiogenic factors by normal/reactive (N/R) or inflammatory (I) areas
      of the osteoarthritic synovial membrane. The effects of interleukin (IL)-1beta
      and chondroitin sulfate (CS) on the expression of pro- and anti-angiogenic
      factors by synovial fibroblasts cells (SFC) were also studied. METHODS: Biopsies
      from N/R or from I areas of osteoarthritic synovial membrane were collected at
      the time of surgery. The inflammatory status of the synovial membrane was
      characterized by the surgeon according to macroscopic criteria, including the
      synovial vascularization, the villi formation and the hypertrophic aspect of the
      tissue. We assessed the expression of CD45, von Willebrand factor and vascular
      endothelial growth factor (VEGF) antigen by immunohistochemistry in both N/R and
      I biopsies. The production of IL-6, -8, VEGF and thrombospondin (TSP)-1 by N/R or
      I synovial cells was quantified by ELISA. SFC were cultured in the absence or in
      the presence of IL-1beta (1 ng/ml) and with or without CS (10, 50, 200 MUg/ml).
      Gene expression of pro-angiogenic factors (VEGF, basic fibroblast growth factor
      (bFGF), nerve growth factor (NGF), matrix metalloproteinase (MMP)-2 and
      angiopoietin (ang)-1) and anti-angiogenic factors (vascular endothelial growth
      inhibitor (VEGI), TSP-1 and -2) were determined by real time RT-PCR. Production
      of VEGI and TSP-1 was also estimated by ELISA. RESULTS: Immunohistochemistry
      showed the increase of lymphocyte infiltration, vascular density and VEGF
      expression in I compared to N/R synovial biopsies. Synovial cells from I areas
      produced more IL-6, IL-8 and VEGF but less TSP-1 than cells isolated from N/R
      synovial biopsies. The expression of pro-angiogenic factors by SFC was stimulated
      by IL-1beta. A time dependent regulation of the expression of anti-angiogenic
      factor genes was observed. IL-1beta stimulated the expression of anti-angiogenic
      factor genes but inhibited it after 24 h. CS reversed the inhibitory effect of IL
      1beta on anti-angiogenic factors, VEGI and TSP-1. CONCLUSIONS: We demonstrated
      that synovial biopsies from I areas expressed a pro-angiogenic phenotype. IL
      1beta induced an imbalance between pro- and anti-angiogenic factors in SFC and CS
      tended to normalize this IL-1beta-induced imbalance, providing a new possible
      mechanism of action of this drug.

PMID- 22409997
TI  - Triaging pandemic flu: pneumonia severity scores are not the answer.
AB  - SETTING: The 2009 H1N1 influenza pandemic caused significant strain on health
      systems worldwide. A tool to triage patients at low risk of requiring intensive
      care services would assist practitioners in safely reducing hospital admission
      rates during pandemic influenza outbreaks. Community-acquired  pneumonia severity
      scores have not been validated for use in pandemic influenza. OBJECTIVE: To
      assess the accuracy of the pneumonia severity index (PSI), CURB-65 and SMRT-CO
      severity scores in predicting patients at low risk of requiring intensive care
      services. DESIGN: Between May and  July 2009, 105 patients admitted with
      laboratory-confirmed pandemic (H1N1) 2009 influenza to Melbourne public hospitals
      were assessed on admission to determine their pneumonia severity scores and
      subsequent need for intensive care unit (ICU) support and length of stay.
      RESULTS: SMRT-CO  was the most accurate score at predicting ICU admission, with
      an area under the curve of the receiver operating characteristic of 0.826. No
      score provided good discrimination of low-risk patients, with respectively 19%,
      21% and 12% requiring ICU admission as predicted by PSI, CURB-65 and SMRT-CO.
      CONCLUSION: Current pneumonia severity scores have insufficient predictive
      ability to safely identify low-risk patients with pandemic (H1N1) 2009 influenza.

PMID- 22409998
TI  - Sensitization to cereals and peanut evidenced by skin prick test and specific IgE
      in food-tolerant, grass pollen allergic patients.
AB  - BACKGROUND: The botanical relation between grass and cereal grains may be
      relevant when diagnosing food allergy to cereals. The aim was to investigate the
      diagnostic specificity of skin prick test (SPT) and specific immunoglobulin E
      (sIgE) tests to cereals and peanut in grass pollen allergic subjects without
      history of, and clinically reactions to foods botanically related to grass.
      METHODS: 70 subjects (41 females; mean age 32 years) and 20 healthy controls (13
      females; mean age 24 years) were tested by open food challenge (OFC) with cereals
      and peanut. SPT and sIgE both with Immulite(r) (Siemens) and ImmunoCAP(r)
      (Phadia) to grass and birch pollen, cereals, peanut and bromelain were performed.
      RESULTS: Of the 65 OFC-negative subjects 29-46% (SPT, depending on cut-off), 20%
      (Immulite) and 38% (ImmunoCAP) had positive results to one or more of the foods
      tested. Controls were negative in all tests. Cross-reactive carbohydrate
      determinants (CCD) as evidenced by reaction to bromelain could explain only a
      minority of the measured IgE-sensitizations. CONCLUSION: Grass pollen allergic
      patients with documented food tolerance to cereals and peanut may express
      significant sensitization. False-positive cereal or peanut allergy diagnoses may
      be a quantitatively important problem both in routine clinical work and
      epidemiological studies.

PMID- 22409999
TI  - The effect of perioperative glucose control on postoperative insulin resistance.
AB  - BACKGROUND & AIMS: Postoperative insulin resistance and the consequent
      hyperglycemia affects clinical outcome. Insulin sensitivity may be modulated by
      preoperative nutrition, adequate pain management and minimal invasive surgery.
      This study aims to disclose the impact of perioperative glucose control on
      postoperative insulin resistance. METHODS: Twenty patients scheduled for elective
      open hepatectomy were enrolled in this prospective, randomized study. In the
      treatment group (n = 9) insulin was administered intravenously to keep blood
      glucose between 6 and 8 mmol/l during surgery. The control group (n = 8) received
      insulin if blood glucose >14 mmol/l. Insulin sensitivity was measured by a
      hyperinsulinemic normoglycemic clamp (0.8 mU/kg/min), performed on all patients
      both on the day before surgery and immediately postoperatively. Plasma cortisol,
      insulin and C-peptide were measured. RESULTS: There was a significant difference
      in mean glucose value during surgery. In the control group 8.8 mmol/l (SD 1.5)
      vs. 6.9 mmol/l (SD 0.4) in the treated group, p = 0.003. In the control group
      insulin sensitivity decreased to 21.9% +/- 16.2% of the preoperative value and in
      the insulin treated group to 46.8 +/- 15.5%, p < 0.005. Insulin levels were
      significantly higher in the treatment group as well as consequently lower C
      peptide levels. CONCLUSIONS: This trial revealed a significant difference in
      postoperative insulin resistance in the group treated with insulin during
      surgery.

PMID- 22410000
TI  - Pulsed ultrasound associated with gold nanoparticle gel reduces oxidative stress
      parameters and expression of pro-inflammatory molecules in an animal model of
      muscle injury.
AB  - BACKGROUND: Nanogold has been investigated in a wide variety of biomedical
      applications because of the anti-inflammatory properties. The purpose of this
      study was to evaluate the effects of TPU (Therapeutic Pulsed Ultrasound) with
      gold nanoparticles (GNP) on oxidative stress parameters and the expression of pro
      inflammatory molecules after traumatic muscle injury. MATERIALS AND METHODS:
      Animals were divided in nine groups: sham (uninjured muscle); muscle injury
      without treatment; muscle injury + DMSO; muscle injury + GNP; muscle injury +
      DMSO + GNP; muscle injury + TPU; muscle injury + TPU + DMSO; muscle injury + TPU
      + GNP; muscle injury + TPU + DMSO + GNP. The ROS production was determined by
      concentration of superoxide anion, modulation of antioxidant defenses was
      determined by the activity of superoxide dismutase, catalase and glutathione
      peroxidase enzymes, oxidative damage determined by formation of thiobarbituric
      acid-reactive substance and protein carbonyls. The levels of interleukin-1beta
      (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were measured as
      inflammatory parameters. RESULTS: Compared to muscle injury without treatment
      group, the muscle injury + TPU + DMSO + GNP gel group promoted a significant
      decrease in superoxide anion production and lipid peroxidation levels (p <
      0.050). It also showed a significant decrease in TNF-alpha and IL-1beta levels (p
      < 0.050) when compared to muscle injury without treatment group. CONCLUSIONS: Our
      results suggest that TPU + DMSO + GNP gel presents beneficial effects on the
      muscular healing process, inducing a reduction in the production of ROS and also
      the expression of pro-inflammatory molecules.

PMID- 22410001
TI  - Biomedical properties and preparation of iron oxide-dextran nanostructures by
      MAPLE technique.
AB  - BACKGROUND: In this work the chemical structure of dextran-iron oxide thin films
      was reported. The films were obtained by MAPLE technique from composite targets
      containing 10 wt. % dextran with 1 and 5 wt.% iron oxide nanoparticles (IONPs).
      The IONPs were synthesized by co-precipitation method. A KrF* excimer laser
      source (lambda = 248 nm, tauFWHM?25 ns, nu = 10 Hz) was used for the growth of
      the hybrid, iron oxide NPs-dextran thin films. RESULTS: Dextran coated iron oxide
      nanoparticles thin films were indexed into the spinel cubic lattice with a
      lattice parameter of 8.36 A. The particle sized calculated was estimated at
      around 7.7 nm. The XPS shows that the binding energy of the Fe 2p3/2 of two thin
      films of dextran coated iron oxide is consistent with Fe3+ oxides. The atomic
      percentage of the C, O and Fe are 66.71, 32.76 and 0.53 for the films deposited
      from composite targets containing 1 wt.% maghemite and 64.36, 33.92 and 1.72
      respectively for the films deposited from composite targets containing 5 wt.%
      maghemite. In the case of cells cultivated on dextran coated 5% maghemite gamma
      Fe2O3, the number of cells and the level of F-actin were lower compared to the
      other two types of thin films and control. CONCLUSIONS: The dextran-iron oxide
      continuous thin films obtained by MAPLE technique from composite targets
      containing 10 wt.% dextran as well as 1 and 5 wt.% iron oxide nanoparticles
      synthesized by co-precipitation method presented granular surface morphology. Our
      data proved a good viability of Hep G2 cells grown on dextran coated maghemite
      thin films. Also, no changes in cells morphology were noticed under phase
      contrast microscopy. The data strongly suggest the potential use of iron oxide
      dextran nanocomposites as a potential marker for biomedical applications.

PMID- 22410002
TI  - A non-peptide receptor inhibitor with selectivity for one of the neutrophil
      formyl peptide receptors, FPR 1.
AB  - The neutrophil formyl peptide receptors (FPR1 and FPR2) are members of the G
      protein coupled receptor family. The signals generated by occupied FPRs are both
      pro-inflammatory and anti-inflammatory. Accordingly, these receptors have become
      a therapeutic target for the development of novel drugs that may be used to
      reduce injuries in inflammatory diseases including asthma, rheumatoid arthritis,
      Alzheimer's disease and cardiovascular diseases. To support the basis for a
      future pharmacological characterization, we have identified a small molecular non
      peptide inhibitor with selectivity for FPR1. We used the FPR1 and FPR2 specific
      ligands fMLF and WKYMVM, respectively, and an earlier described ratio technique,
      to determine inhibitory activity combined with selectivity. We show that the
      compound 3,5-dichloro-N-(2-chloro-5-methyl-phenyl)-2-hydroxy-benzamide
      (BVT173187) fulfills the criteria for an FPR1 inhibitor selective for FPR1 over
      FPR2, and it inhibits the same functional repertoire in neutrophils as earlier
      described peptide antagonists. Accordingly, the new inhibitor reduced neutrophil
      activation with FPR1 agonists, leading to mobilization of adhesion molecules
      (CR3) and the generation of superoxide anion from the neutrophil NADPH-oxidase.
      The effects of a number of structural analogs were determined but these were
      either without activity or less active/specific than BVT173187. The potency of
      the new inhibitor for reduction of FPR1 activity was the same as that of the
      earlier described FPR1 antagonist cyclosporine H, but signaling through the C5aR
      and CXCR (recognizing IL8) was also affected by BVT173187.

PMID- 22410003
TI  - Characterisation of Na(v) types endogenously expressed in human SH-SY5Y
      neuroblastoma cells.
AB  - The human neuroblastoma cell line SH-SY5Y is a potentially useful model for the
      identification and characterisation of Na(v) modulators, but little is known
      about the pharmacology of their endogenously expressed Na(v)s. The aim of this
      study was to determine the expression of endogenous Na(v) alpha and beta subunits
      in SH-SY5Y cells using PCR and immunohistochemical approaches, and
      pharmacologically characterise the Na(v) isoforms endogenously expressed in this
      cell line using electrophysiological and fluorescence approaches. SH-SY5Y human
      neuroblastoma cells were found to endogenously express several Na(v) isoforms
      including Na(v)1.2 and Na(v)1.7. Activation of endogenously expressed Na(v)s with
      veratridine or the scorpion toxin OD1 caused membrane depolarisation and
      subsequent Ca(2+) influx through voltage-gated L- and N-type calcium channels,
      allowing Na(v) activation to be detected with membrane potential and fluorescent
      Ca(2) dyes. MU-Conotoxin TIIIA and ProTxII identified Na(v)1.2 and Na(v)1.7 as
      the major contributors of this response. The Na(v)1.7-selective scorpion toxin
      OD1 in combination with veratridine produced a Na(v)1.7-selective response,
      confirming that endogenously expressed human Na(v)1.7 in SH-SY5Y cells is
      functional and can be synergistically activated, providing a new assay format for
      ligand screening.

PMID- 22410004
TI  - Changes in morphine-induced activation of cerebral Na(+),K(+)-ATPase during
      morphine tolerance: biochemical and behavioral consequences.
AB  - There is ample evidence of the biological changes produced by the sustained
      activation of opioid receptors. We evaluated the adaptive changes of cerebral
      Na(+),K(+)-ATPase in response to the sustained administration of morphine
      (minipumps, 45mg/kg/day, 6 days) in CD-1 mice and the functional role of these
      changes in opioid antinociception. The antinociceptive effect of morphine as
      determined with tail-flick tests was reduced in morphine-tolerant mice. There
      were no significant changes in the density of high-affinity Na(+),K(+)-ATPase
      alpha subunits labeled with [(3)H]ouabain in forebrain membranes from morphine
      tolerant compared to those of morphine-naive animals. Western blot analysis
      showed that there were no significant differences between groups in the changes
      in relative abundance of alpha(1) and alpha(3) subunits of Na(+),K(+)-ATPase in
      the spinal cord or forebrain. However, the morphine-induced stimulation of
      Na(+),K(+)-ATPase activity was significantly lower in brain synaptosomes from
      morphine-tolerant mice (EC(50)=1.79+/-0.10MUM) than in synaptosomes from morphine
      naive mice (EC(50)=0.69+/-0.12MUM). Furthermore, adaptive alterations in the time
      course of basal Na(+),K(+)-ATPase activity were observed after sustained morphine
      treatment, with a change from a bi-exponential decay model (morphine-naive mice)
      to a mono-exponential model (morphine-tolerant mice). In behavioral studies the
      antinociceptive effects of morphine (s.c.) in the tail-flick test were dose
      dependently antagonized by ouabain (1 and 10ng/mouse, i.c.v.) in morphine-naive
      mice, but not in morphine-tolerant mice. These findings suggest that during
      morphine tolerance, adaptive cellular changes take place in cerebral Na(+),K(+)
      ATPase activity which are of functional relevance for morphine-induced
      antinociception.

PMID- 22410005
TI  - A high model for end-stage liver disease score should not be considered a
      contraindication to living donor liver transplantation.
AB  - OBJECTIVE: To analyze the outcomes of patients with high Model for End-Stage
      Liver Disease (MELD) scores who underwent adult-to-adult live donor liver
      transplantation (A-A LDLT). MATERIALS AND METHODS: From September 2002 to October
      2010, a total of 152 adult patients underwent A-A LDLT in our institution.
      Recipients were stratified into a low MELD score group (Group L; MELD score<=30)
      and a high MELD score group (Group H; MELD score>30) to compare short-term and
      long-term outcomes. RESULTS: Of the 152 adult patients who underwent A-A LDLT, 9
      were excluded from the analysis because they received ABO-incompatible grafts.
      Group H comprised 23 and Group L 120 patients. The median follow-up was 21.5
      months (range, 3 to 102 m). The mean MELD score was 15.6 in Group L and 36.7 in
      Group H. There were no significant differences in the mean length of stay in the
      intensive care unit (Group L: 3.01 days vs Group H: 3.09 days, P=.932) or mean
      length of hospital stay (Group L: 17.89 days vs. Group H: 19.91 days, P=0.409).
      There were no significant differences in 1-, 3-, or 5-year survivals between
      patients in Groups L versus H (91.5% vs 94.7%; 86.4% vs 94.7%; and 86.4% vs
      94.7%; P=.3476, log rank). CONCLUSION: The short-term and long-term outcomes of
      patients with high MELD scores who underwent A-A LDLT were similar to those of
      patients with low MELD scores. Therefore, we suggest that high MELD scores are
      not a contraindication to LDLT.

PMID- 22410006
TI  - Analysis of donor risk factors associated with graft outcomes in orthotopic liver
      transplantation.
AB  - BACKGROUND: In orthotopic liver transplantation (OLT), the critical shortage of
      organ donors is the reason for accepting marginal donors. Although the outcome of
      OLT does not entirely seem to have been affected by the use of such donors
      identification of predictive risk factors is challenging. This study sought to
      identify significant risk factors associated with graft outcomes in our
      institute. METHODS: We retrospectively analyzed donor-associated factors for
      recipients who underwent liver transplantation from January 2002 to December 2009
      for displaying primary dysfunction (PDF) as primary nonfunction (PNF) and initial
      poor function (IPF). RESULTS: We examined 97 post-liver transplant patients
      (male:female 70:27) whose average age was 52.74 years. The majority of
      indications for OLT were hepatitis B and/or C cirrhosis, alcoholic cirrhosis, and
      hepatocellular carcinoma. The incidence of PDF was 31.9% (31/97) including 7.2%
      PNF (7/97) and 24.7% IPF (24/97), versus 68.1% (66/97) with immediate function.
      The donors last serum alanine aminotransferase value being more than 65 IU/L was
      the only risk factor for poor graft function (P=.034). Donor peak and last serum
      sodium were potential risk factors. CONCLUSION: Although many factors including a
      high serum sodium level are associated with a marginal liver graft, Last donor
      alanine aminotransferase level was the only significant factor that predicted the
      PDF.

PMID- 22410007
TI  - Magnetic resonance cholangiography in living donor liver transplantation:
      comparison of preenhanced and post-gadolinium-enhanced methods.
AB  - OBJECTIVE: The purpose of this study was to evaluate the image quality and
      diagnostic accuracy of postgadolinium complex of diethylenetriaminepentaacetic
      acid (GD-DTPA)-enhanced magnetic resonance cholangiography (MRC) in donor
      selection. MATERIALS AND METHODS: Donors (n=228) with both preoperative MRC and
      intraoperative cholangiography (IOC) were enrolled in this study. MRC pre- and
      post-GD-DTPA enhancement were performed using 1.5-T magnetic resonance imaging.
      The signal-to-noise ratio (SNR) of liver parenchyma and contrast-to-noise ratio
      of bile duct, as well as the contrast between bile duct and liver parenchyma,
      were calculated. The biliary anatomy correlation with the IOC during hepatectomy
      and patient prognosis were also evaluated. RESULTS: Quantitative results of the
      SNR of the liver parenchyma post-GD-DTPA were statistically significantly lower
      than preenhanced MRC (2.69 times reduced from the preenhanced MRC). The contrast
      of the bile duct and liver parenchyma in post-GD-DTPA were significantly higher
      than the preenhancement MRC. The anatomic diagnostic accuracy rate of post-GD
      DTPA MRC was 92.9%. The sensitivity and specificity of GD-PTPA MRC were 85% and
      96%, respectively. GD-DTPA-enhanced MRC has higher accuracy than the preenhanced
      MRC (92.9% vs 75%). The concurrence between GD-DTPA-enhanced MRC and IOC were
      commendable (kappa=0.9). The posttransplant biliary complication rate was 5.5%,
      and the 3-year survival rate was 91.2% in the recipients. CONCLUSION: GD-DTPA, a
      paramagnetic metal, can shorten the T1 and T2 relaxation values of surrounding
      protons. This decreases the signal of the liver parenchyma and brightens the
      biliary anatomy. It can improve the image quality of MRC and increase the
      diagnostic accuracy of the biliary tract classification. It is mandatory in the
      "donor and recipient surgery during the LDLT".

PMID- 22410008
TI  - Importance of awareness of perioperative social and physical situations of living
      donors for liver transplantation.
AB  - INTRODUCTION: Transplantation in Japan still depends on living donors even after
      the new revised law. We must pay attention to protect living donors. PATIENTS AND
      METHODS: Perioperative qualities of life after living donation for liver
      transplantation were assessed with questionnaires including the Medical Outcomes
      Study 36-Item Short-Form Health Survey version 2 (SF36-v2). Nonparametric Mann
      Whitney tests were used to determine statistical significance. P values<.05 were
      considered significant. RESULTS: Thirty-one among 33 donors answered
      questionnaires (93.9%). The 15 men and 16 women of average age of 39.7 years had
      a median hospital stay of 16 days and median duration after surgery of 78 months.
      Ten of 33 (35.7%) donors considered themselves to be the only possibility. The
      decision to a donor was established prior to informed consent in 23 donors
      (74.1%). Six months were required for them to experience a full recovery after
      donor surgery. Hamilton depression/anxiety score was significantly increased
      among donors who considered themselves to be the only possibility or those who
      had decided prior to informed consent. SF36-v2 revealed a significant decrease in
      social functioning among donors who did not have sufficient time to decide before
      surgery. General health was significantly decreased among donors who required
      more than 6 months for full recovery. Perioperative management of pain influenced
      general health, physical role, bodily pain, and physical functioning. CONCLUSION:
      We must pay attention to depression and anxiety among living donors. More care
      should be focused on pain control and sharing of information of postoperative
      courses.

PMID- 22410009
TI  - Postoperative liver dysfunction in living donors after left-sided graft
      hepatectomy: portal venous occlusion of the medial segment after lateral
      segmentectomy and hepatic venous congestion after left lobe hepatectomy.
AB  - BACKGROUND: The aim of this study was to evaluate how sacrifice of the portal
      vein and/or hepatic vein affects remnant liver dysfunction after lateral
      segmentectomy or left lobe hepatectomy. MATERIALS AND METHODS: Among 130 patients
      who underwent donor hepatectomy between March 2002 and July 2011, we enrolled
      lateral segment (n=15) and left lobe donors (n=40). We evaluated the
      postoperative courses and the territory of venous obstruction or congestion based
      on the sacrificed portal vein or hepatic vein after the donor operation: lateral
      segment grafts (P4a, P4b, LV4) and left lobe grafts (MV5, MV8) according to the
      results analyzed by MeVis Distant Service. RESULTS: Among lateral segment donors,
      the predicted sacrificed territory of portal vein and hepatic vein was 14.3%
      (7.3%-19.4%) in P4a+4b: (P4a: 8.6%, P4b: 5.8%) and 2.9% (0%-8.4%) in LV4,
      respectively. On the other hand, in left lobe donors, the predicted congestive
      territory of the hepatic vein was 17.6% (2.8%-33.0%) in MV5+8 (7.8% in MV5 and
      9.8% in MV8, respectively). The incidence of patients whose postoperative peak
      aspartate aminotransferase (AST) or alanine aminotransferase levels were higher
      than 500 IU/L was 20% in the lateral segment donors and 5% in the left lobe
      donors. The peak postoperative AST levels and territory of MV5+8 showed a
      significant positive correlation (R=0.569, P<.05) among left lobe donors.
      CONCLUSION: Territories of P4 in lateral segment donors and MV5+8 in left lobe
      donors impacted postoperative liver dysfunction. It is important to recognize the
      precise territory of the portal vein and the hepatic vein before the donor
      operation.

PMID- 22410010
TI  - Difference of regeneration potential between healthy and diseased liver.
AB  - BACKGROUND: We sought to evaluate total and segmental liver regeneration by
      comparing preoperative computed tomographic (CT) volumetry and CT volumetry on
      postoperative day (POD) 7 after a right hepatectomy, in patients with various
      status and surgical indications. METHOD: We included 36 patients who underwent
      right lobectomy for living donor liver transplantation (healthy group), and 29
      for hepatocellular carcinoma treatment (disease group). All of the disease group
      patients were Child-Turcotte-Pugh (CTP) class A. The regeneration of lateral,
      medial segment and total remnant liver volumes were assessed on POD 7 using a CT
      based program. Total volumes and segmental volumes were measured for total liver,
      future liver remnant (FLR), and liver remnant. We calculated total and segmental
      early regeneration indexes, defined as [(VLR-VFLR)/VFLR]*100, where VLR is volume
      of the liver remnant and VFLR is volume of the FLR. RESULT: The VLR at POD 7
      showed a 72.9% increase in volume among the healthy versus 55% in the disease
      group, (P=.012) In the disease group, segmental volume and regeneration indexes
      were also significantly lower than among the healthy group: 59.0% versus 46.9% in
      the medial and 86.8% versus 57.7% in the lateral segment (P=.023 and P<.001)
      respectively. CONCLUSION: The volume regeneration potential in diseased livers is
      significantly lower than that of a normal, healthy liver. So, we must consider a
      patient's liver status and volume profile before an extensive liver.

PMID- 22410011
TI  - Donor quality of life after living donor liver transplantation: single-institute
      experience.
AB  - AIM: Living donor liver transplantation (LDLT) has been widely accepted because
      of the severe shortage of hepatic grafts. However, the healthy donor is exposed
      to risks of morbidity and mortality. In this study, we analyzed medical,
      functional, and psychological outcomes of donors after hepatectomy for liver
      donation. PATIENTS AND METHODS: Among 41 donor hepatectomy cases for LDLT
      performed in our institute from January 1994 to May 2011, we reviewed the medical
      records (liver function tests, complications, etc) of 27 subjects who donated to
      recipients older than 12 years. We also performed a questionnaire survey based on
      the Japanese Short Form-36 version 2 Health Survey scales as a measure of
      physical and mental health, to which 31 subjects responded. RESULTS: Six of the
      27 donors experienced prolonged jaundice. Their ratios of graft volume/standard
      donor liver volume (GV/SDLV) were higher than those of the 21 donors without
      prolonged jaundice (60.0% vs 41.5%). According to the questionnaires, social
      functioning among those having undergone emergency hepatectomy as well as general
      health perceptions declined in those with postoperative complications. Physical
      component summary declined among those having undergone emergency hepatectomy and
      with postoperative complications. CONCLUSION: In liver donation from a living
      donor, massive hepatectomy should be avoided. A ratio of GV/SDLV around 50% seems
      reasonable. Donors with emergency transplantations or postoperative complications
      must be more carefully followed after donor hepatectomy.

PMID- 22410012
TI  - Change in donor quality of life after living donor liver transplantation surgery:
      a single-institution experience.
AB  - AIM: Changes in quality of life (QOL) of donors after living donor liver
      transplantation surgery were studied using Short Form 36 (SF-36) to evaluate
      physical health and the Profile of Mood States (POMS) to evaluate mood. METHODS:
      Among the 28 donors who had undergone surgery at our hospital, 21 donors replied
      to our questionnaire (recovery rate: 75%). Changes in the QOL of donors were
      examined based on the results of pre- and postoperative SF-36 and POMS and a
      questionnaire survey. RESULTS: The donors included 12 men and nine women with a
      mean age of 43 years. One donor operation was complicated by biliary stenosis.
      The SF-36 results showed significant postoperative decline in physical function
      and increase in pain, but no other significant changes. The POMS results showed
      no significant differences, with the mean values for anxiety, depression, anger,
      vitality, and confusion all recovering postoperatively. The questionnaire results
      indicated that all subjects had recovered physical function, but 24% of subjects
      felt wound-related physical symptoms and 19% felt anxiety concerning their future
      health. CONCLUSIONS: Some donors had symptoms that persisted for comparatively
      long periods postoperatively and considered that long-term outpatient observation
      was required. No significant psychological changes were found, but donors felt
      anxiety about their future health and considered that patient meetings would be
      useful and that adequate outpatient health guidance should be provided.

PMID- 22410013
TI  - Single-port laparoscopy-assisted donor right hepatectomy in living donor liver
      transplantation: sensible approach or unnecessary hindrance?
AB  - BACKGROUND: Single-port laparoscopic (SPL) surgery has rapidly gained attention
      worldwide. Since May 2008, we have propagated the use of SPL surgery, mainly for
      cholecystectomy and appendectomy. Recently, we have used this modality of
      minimally invasive surgery for various liver surgeries. We hereby discuss our
      outcomes of SPL-assisted donor right hepatectomies. METHODS: The preoperative
      workup is the same as for a standard donor hepatectomy. We retrospectively
      reviewed the data of 150 patients who underwent donor right hepatectomy from
      October 2008 to May 2011. We divided them into 3 groups depending on the type of
      surgical procedure. RESULTS: Among 150 patients, 20 underwent laparoscopy
      assisted donor right hepatectomy (LADRH); 40 underwent single-port laparoscopy
      assisted donor right hepatectomy (SPLADRH); and 90 underwent open donor right
      hepatectomy (ODRH). The donor demographics were comparable among the groups.
      Postoperative complication and reoperation rates revealed no significant
      differences. The SPLADRH group showed the lowest level of postoperative pain,
      thereby leading to a better quality of life postoperatively. CONCLUSIONS: SPLADRH
      seems to be a simple, feasible approach.

PMID- 22410014
TI  - Standardized less invasive living donor hemihepatectomy using the hybrid method
      through a short upper midline incision.
AB  - BACKGROUND: Recently, applications of less invasive liver surgery in living donor
      hepatectomy (LDH) have been reported. The objective of this study was to evaluate
      the safety and efficacy of a hybrid method with a midline incision for LDH.
      METHODS: Hemihepatectomy using the hybrid method was performed in the fifteen
      most recent among 150 living donors who underwent surgery between 1997 and August
      2011. Six donors underwent right hemihepatectomy and 9 underwent left
      hemihepatectomy. An 8-cm subxiphoid midline incision was created for hand
      assistance during liver mobilization and graft extraction. After sufficient
      mobilization of the liver, the hand-assist/extraction incision was extended to 12
      cm for the right hemihepatectomy and 10 cm for a left hemihepatectomy. Encircling
      the hepatic veins and hilar dissection were performed under direct vision.
      Parenchymal transection was performed with the liver hanging maneuver. Bile duct
      division was performed after visualizing the planned transection point by
      encircling the bile duct using a radiopaque marker filament under real-time C-arm
      cholangiography. RESULTS: All procedures were completed without any extra
      subcostal incision. All grafts were safely extracted through the 10-12-cm upper
      midline incision without mechanical injury. No donors required an allogeneic
      transfusion; all of them have returned to their preoperative activity levels.
      CONCLUSION: LDH by the hybrid method with a short upper midline incision is a
      safe procedure.

PMID- 22410015
TI  - Living donor liver transplantation for the patients with portal vein thrombosis:
      use of an interpositional venous graft passed posteriorly to the pancreatic
      parenchyma without using jump graft.
AB  - BACKGROUND: It is difficult to reconstruct the portal vein (PV) using a long
      interpositional venous graft in living donor liver transplant (LDLT) patients
      with portal vein thrombosis (PVT), which involves the confluence of the superior
      mesenteric vein (SMV) and splenic vein (SV). We successfully performed LDLT for
      three patients with PVT using an interpositional vascular conduit passing
      posterior to the pancreas without a jump graft. METHODS: Three of 130 patients
      who underwent LDLT in our hospital between March 2002 and June 2011 required this
      technique. After indentifying the location of the SMV, SV and gastrocolic trunk,
      we ligated and cut the posterior superior pancreaticoduodenal vein and other
      short branches from the PV. The PV was drawn inferiorly to the pancreas and
      transected at the confluence of SMV and SV. The external iliac vein or internal
      jugular vein was sacrificed as a graft for anastomosis to the cut end of the SMV
      using 6-0 polypropylene running sutures. Then the venous graft was drawn
      superiorly to the pancreas by passing it posterior to the pancreas parenchyma for
      anastomosis to the liver graft PV. The interpositional vein was placed posterior
      to the pancreas where the PV used to be. RESULTS: All three patients displayed
      favorable postoperative courses with the Doppler ultrasound demonstrating good
      portal flow perioperatively. The postoperative portogram demonstrated patency of
      the vascular graft. CONCLUSION: This method is easy and helpful to treat portal
      vein thrombosis, by providing the shortest route between the PV of the donor and
      the SMV of the recipient.

PMID- 22410016
TI  - Pain management of living liver donors with morphine with or without ketorolac.
AB  - BACKGROUND: To compare the efficacy and dose requirements for intravenous (IV)
      patient-controlled analgesia (PCA) with morphine only versus morphine with
      ketorolac for living liver donors after partial hepatectomy. PATIENTS AND
      METHODS: Eighty living liver donors who had undergone partial hepatectomy
      received 3 days of IV PCA for postoperative pain control. Some were prescribed a
      PCA with morphine alone (group I) or morphine with ketorolac (group II), while
      both had a rescue dose of IV fentanyl (25 MUg). The daily consumption of
      morphine, pain score, and frequency of rescue fentanyl doses were compared
      retrospectively using the Mann-Whitney U test and the incidence of side effects
      with chi-square tests; a P value of .05 was regarded as significant. All the data
      are shown as mean values+/-standard deviations. RESULTS: The 80 subjects were
      distributed as 57 group I and in 23 group II patients. The daily consumption of
      morphine, Visual Analogue Scale (VAS) and side effects were not different between
      the groups, but group II required significantly fewer rescue doses to achieve
      pain relief. CONCLUSION: Both regimens provided acceptable pain control with
      daily VAS less than 3. The use of ketorolac in the PCA did not reduce the daily
      total morphine requirements with a similar incidence of side effects but a
      significantly reduced requirement for rescue doses, which subsequently reduced
      the work load of personnel in the pain control service.

PMID- 22410017
TI  - Postoperative pain and influencing factors among living liver donors.
AB  - PURPOSE: In Korea, living donor transplantation is increasing steadily as a life
      saving alternative. It is essential to provide living donors the mental and
      physical care they need throughout their lives including postoperative period.
      Therefore, this study explored postoperative pain among living liver donors.
      METHODS: We used a convenience sampling at a university-affiliated hospital from
      March 1 to August 30, 2009 including 102 subjects. Face-to-face interviews with
      questionnaires and medical records were used to assess postoperative pain levels,
      state and trait anxiety as well as satisfaction. Data were analyzed using SPSS
      14.0 (SPSS Inc., Chicago, Ill, USA). RESULTS: Average age of donors was 28.9+/
      7.7 years (ranged 16 to 53) with 70.6% male. Most donors (80.4%, n=82) were
      immediate family members. Ninety-one (89.2%) participants made the decision by
      themselves. To control postoperative pain, all participants had patient
      controlled anesthesia with several types of analgesics as prescribed by
      physician's preference. The mean values of state anxiety, trait anxiety, and
      satisfaction in this study were 2.1+/-1.89, 36.7+/-7.25 and, 8.9+/-1.79,
      respectively. Multivariate analysis showed that trait anxiety and number of
      analgesics use were significantly associated with postoperative pain. Overall,
      approximately 29.7% of total variability in postoperative pain could be explained
      by the nine variables in this model (R2=0.297, F9,102=4.28, (P<.001). There was
      no multicollinearity checked by tolerance, variation inflation factor, or
      condition index. CONCLUSION: This study of postoperative pain among living liver
      donors may contribute to developing the safest, most effective strategy to
      relieve postoperative pain after living liver donation.

PMID- 22410018
TI  - Effect of university of wisconsin and histidine-tryptophan-ketoglutarate
      preservation solutions on blood potassium levels of patients undergoing living
      donor liver transplantation.
AB  - BACKGROUND: The potassium content of University of Wisconsin solution (UW) is 125
      mEq/L and that of histidine-tryptophan-ketoglutarate solution (HTK) only 9 mEq/L.
      The aim of the present study was to analyze their effects to change potassium
      levels on reperfusion among patients undergoing living-donor liver
      transplantation. METHODS: Anesthesia records of adult living-donor liver
      transplant patients were reviewed retrospectively. Patients received liver graft
      preserved in UW were grouped in group I (GI) and HTK in group II (GII). The
      potassium levels in the anheptic phase were compared with those 5 minutes after
      reperfusion using paired Student t tests. P values of <.05 were regarded to be
      significant. RESULTS: Eighty-five GI patients showed the potassium significantly
      decreased from 3.76+/-0.70 to 3.60+/-0.74, whereas the change among 355 GII
      patients was almost unremarkable: 4.00+/-0.57 to 3.96+/-0.06 mEq/L. CONCLUSIONS:
      Although UW contains a higher potassium content, it seems to have no negative
      impact on changes in serum potassium levels; in contrast it decreased the
      potassium level significantly at 5 minutes after reperfusion. Both preservation
      solutions maintain the patients' potassium levels within the normal range.

PMID- 22410020
TI  - Experience using extended criteria donors in first 100 cases of deceased donor
      liver transplantation in Japan.
AB  - Because of the serious organ shortage in Japan, the use of extended criteria (EC)
      donors is inevitable to increase the number of deceased donors. However, the
      influence of this practice on recipient outcomes has not been clarified yet. We
      analyzed donor and recipient factors to determine whether those factors,
      especially from EC donors impacted early recipient outcomes. From February 1999
      to January 2011, 100 deceased liver transplantations were performed in Japan,
      including 85 consecutive adult cases (age>=18 years) who were studied to evaluate
      whether 6 recipient and 16 donor factors affected 3-month (90-day) recipient
      survival. Upon univariate analysis, Model for End-stage Liver Disease (MELD)
      score>=25 (P=.018), donor age>=55 years (P=.040), and cold ischemia time
      (CIT)>=10 hours (P=.00013) significantly reduced 3-month survival. Multivariate
      analysis confirmed the independent contributions of, three adverse factors
      including MELD score>=25 (P=.0133, odds ratio [OR]=12.3, 95% confidence interval
      [CI]=1.7-90.3), donor age>=55 years (P=.013, OR=14.0, 95% CI=1.6-119.5), and
      CIT>=10 hours (P=.0024, OR=67.6, 95% CI=4.5-1024.9). Three-month recipient
      survivals with 0, 1, 2, and 3 positive factors were 100% (n=34), 94.4% (n=36),
      53.8% (n=13), and 0% (n=2), respectively (P<.0001). In conclusion, to improve
      recipient short-term survivals, minimizing CIT is the first priority. In the long
      term, we must promote deceased donation to reduce recipient MELD scores by
      shortening the waiting time, and revise the allocation system to minimize CIT by
      giving priority to the local area.

PMID- 22410019
TI  - Recombinant human soluble thrombomodulin (ART-123) prevents warm ischemia
      reperfusion injury in liver grafts from non-heart-beating donors.
AB  - BACKGROUND: Liver transplantation is an established treatment for end-stage liver
      disease. However, an ongoing problem worldwide concerning this treatment is the
      shortage of grafts. Although transplantation using grafts from non-heart-beating
      donors (NHBDs) is considered a promising solution, some researchers have reported
      that these liver grafts are associated with primary graft nonfunction and biliary
      complications. The purpose of this study was to establish a safe technique
      procuring liver grafts from marginal donors such as NHBDs. MATERIALS AND METHODS:
      Male Wistar rats were divided into three groups: (1) the heart-beating (HB)
      group, whose livers were retrieved from HB donors; (2) the non-HB (NHB) group,
      whose livers were retrieved from NHBDs that had experienced an apnea-induced
      agonal condition (for this group, livers were subjected to warm ischemia for 30
      minutes after cardiac arrest); and (3) the recombinant human soluble
      thrombomodulin (ART-123) group, whose livers were retrieved in the same manner as
      the NHB group but pretreated with ART-123 (1 mg/kg) at the agonal stage. The
      livers were reperfused for 60 minutes with oxygenated Krebs-Henseleit bicarbonate
      buffer after cold preservation for 6 hours. RESULTS: Bile production and portal
      flow volume in the ART-123 group were significantly higher than those in the NHB
      group. Alanine aminotransferase levels in the ART-123 group were significantly
      lower than those in the NHB group. Histological findings showed the narrowing of
      sinusoidal spaces and necroses in the NHB group were more severe than those in
      the ART-123 group. CONCLUSIONS: These results suggest that thrombomodulin may
      improve the viability of liver grafts from NHBDs.

PMID- 22410021
TI  - Propofol attenuates ischemic reperfusion-induced formation of lipid peroxides in
      liver transplant recipients.
AB  - OBJECTIVE: Ischemic reperfusion (IR) injury is known to have an important
      influence on the success of transplant surgery and the occurrence of
      complications. Malondialdehyde (MDA) is an intermediate metabolite of lipid
      peroxidation resulting from IR-induced reactive oxygen species. This study was
      designed to investigate the protective effects of propofol on IR injury in liver
      transplant recipients. METHODS: We analyzed 19 recipients prospectively by
      measuring the blood levels of MDA at nine predefined intervals; before induction
      of anesthesia (baseline, T0), 1 hour after surgical incision (T1), 1 minute
      before reperfusion (T2), 30 seconds after reperfusion (T3), as well as 1, 3, 5,
      30, and 60 minutes thereafter (T4-8). These patients were randomly allocated to
      two groups. The propofol group received an infusion (2 mg/kg per hr) after an
      induction bolus (2 mg/kg). The control group was prescribed midazolam (0.2 mg/kg)
      for induction without intravenous anesthetic infusion for maintenance. RESULTS:
      The highest MDA level occured at T6 in the controls and T7 in the propofol group.
      Compared with the blood levels at baseline, the MDA levels increased
      significantly at T2-T8 among controls versus T2, T3, T4, and T7 in the propofol
      group. Compared to the control group, propofol significantly lowered MDA values
      at T5-T8. CONCLUSION: There were significantly higher MDA levels among the
      control versus the propofol group at 3, 5, 30, and 60 minutes after reperfusion
      in liver transplant recipients.

PMID- 22410022
TI  - The effects of intermittent inflow occlusion and hepatic steatosis on
      postoperative liver functions in living liver donors undergoing right
      hepatectomy.
AB  - BACKGROUND: Intermittent inflow occlusion (IIO) is a safe, effective method to
      reduce blood loss during liver resection and preserve function even among
      patients with underlying diseases such as steatosis and cirrhosis. Therefore, we
      evaluated the impact of IIO on postoperative liver function tests (LFT) and on
      morbidity among living liver donors undergoing a right hepatectomy, including
      donors with mild degrees (5%-30%) of macrovesicular steatosis (MaS). METHODS: We
      retrospectively reviewed the medical records of 186 living liver donors from
      August 2008 to September 2010. Donors were divided into two groups according to
      group IIO (n=81) versus Controls (no IIO, n=105). Within each group, donors were
      subdivided to evaluate Peak values of LFTs and complications into according the
      degree of MaS: group I_5 (n=36); IIO+<5% MaS, group I_30 (n=45); IIO+5%-30% MaS,
      group C_5 (n=55); Control+<5% MaS, and group C_30 (n=50); Control+5%-30% MaS.
      RESULTS: Peak aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
      among IIO were significantly higher than Non-IIO. These values in groups I_5 and
      I_30 were significantly higher than groups C_5 and C_30, respectively (all,
      P<.01). The overall postoperative complications were comparable between groups
      IIO and Non-IIO, but significantly higher among group I_30 than groups I_5
      (P=0.024) and C_30 (P=.012). CONCLUSIONS: Application of IIO in donors with mild
      macrosteatosis undergoing right hepatectomy showed significantly higher
      postoperative peak liver functions tests and number of overall complications than
      those without IIO.

PMID- 22410023
TI  - High model for end-stage liver disease score as a predictor of survival during
      long-term follow-up after liver transplantation.
AB  - BACKGROUND: The allocation of cadaveric livers for transplantation in the United
      States is now based on the severity of illness as determined by the Model for End
      Stage Liver Disease (MELD), which was developed to predict short-term mortality
      in patients with cirrhosis. However, its impact to predict posttransplantation
      survival is controversial. The objective of this study was to determine the
      association of various pretransplantation risk factors, including the MELD score
      and whether its use to allocate organs is likely to lead to overall poorer
      outcomes of liver transplantation. METHODS: The 1,032 consecutive adult liver
      transplantation patients at King's College Hospital between 2 January 1994 and 29
      December 2001 were examined for 9 preoperative risk factors, including MELD
      score, using univariate and multivariate techniques. Based on their
      pretransplantation MELD scores, we categorized recipients as low (<15) medium (15
      25), or high (>25). Kaplan-Meier patient survival analysis was used to identify
      differences in outcomes. RESULTS: The patients had a mean age of 47.2 years and
      mean posttransplantation follow-up of 5.3 years. Univariate analysis showed
      recipient diabetes mellitus, renal dysfunction, and pretransplantation MELD score
      to be associated with patient survival. Multivariate analysis showed the MELD
      score to be significantly associated with death during long-term follow-up.
      CONCLUSIONS: A high pretransplantation MELD score was associated with poor
      posttransplantation outcomes.

PMID- 22410024
TI  - Model for end-stage liver disease and model for end-stage liver disease-Na scores
      predict both before-listing and wait-list mortality.
AB  - BACKGROUND: Due to the organ shortage, many patients die without transplantation,
      even before completing an evaluation for candidacy. We analyzed outcomes after
      patient referral and factors associated with mortality both before and after
      listing for cadaveric donor liver transplantation. METHODS: We analyzed 132
      consecutive patients who were evaluated for candidacy for cadaveric donor liver
      transplantation between 2003 and 2010. RESULTS: The study included 69 men and 63
      women of median age 49 years (range, 1-65). Etiologies of diseases were acute
      hepatic failure (n=19), liver cirrhosis due to hepatitis B or C (n=36), primary
      biliary cirrhosis (n=19), nonviral cirrhosis (n=14), hepatocellular carcinoma
      (n=13), or other causes (n=31). After evaluation for candidacy, we listed 68
      (52%), subjects whereas 24 (18%) died before listing. Factors affecting death
      before listing were the levels of albumin (P<.001), bilirubin (P<.001), sodium
      (P<.001), international normalized ratio (INR; P<.001), Model for End-stage Liver
      Disease (MELD) score (P<.001), MELD-Na score (P<.001), and Child-Pugh-Turcotte
      (CPT) score (P<.001). Based on multivariate Cox regression analysis, MELD score
      (hazard ratio [HR] 1.201, P=.017), MELD-Na score (HR 1.244, P=.014), CPT score
      (HR 1.468, P=.033), and INR (HR 0.491, P=.027) were independently associated with
      death before listing. Among 68 listed candidates, 11 (16%) underwent
      transplantation, whereas 29 (43%) died without transplantation. Based on
      multivariate Cox regression analysis, MELD score (HR 1.102, P=.001), MELD-Na
      score (HR 1.128, P=.001), and CPT score (HR 1.282, P=.038) independently
      predicted wait-list mortality. All 11 patients who underwent cadaveric liver
      transplantation were alive at 29 months (range, 1-55) after transplantation.
      CONCLUSIONS: Patients with a higher MELD, higher MELD-Na, and higher CPT score at
      referral were at greater risk for death without transplantation, especially
      before listing. Evaluation for transplantation candidacy is a time-consuming
      process. Therefore, earlier referral is mandatory to achieve successful listing
      for transplantation.

PMID- 22410025
TI  - Which score system can best predict recipient outcomes after living donor liver
      transplantation?
AB  - INTRODUCTION: Many scoring systems have been suggested to predict the outcomes of
      deceased donor liver transplantations. The aims of this study were to compare the
      Model for End-Stage Liver Disease (MELD) score with respect to other scores among
      patients who underwent living donor liver transplantation (LDLT) seeking to
      evaluate the best system to correlate with postoperative outcomes after LDLT.
      METHODS: We analyzed retrospectively data from 202 adult patients who underwent
      LDLT from January 2008 to July 2010. We calculated preoperative MELD, MELD
      sodium, MELD to serum sodium ratio (MESO), integrated MELD, United Kingdom MELD,
      Child-Turcotte-Pugh, Acute Physiology and Chronic Health evaluation II (APACHE
      II), and Sequential Organ Failure Assessment (SOFA) scores in all patients. We
      analyzed the correlation of each score with postoperative laboratory results, as
      well as survival at 1, 3, 6 and 12 months after LDLT. RESULTS: There was
      significant positive correlation between all scores and peak total bilirubin
      during the first 7 days after LDLT. The MELD score showed the greatest
      correlation with peak total bilirubin (r=0.745). APACHE II and SOFA scores at 6
      months and 1 year after LDLT and MESO score at 1 year after LDLT showed
      acceptable discrimination performance {area under the receiver operating
      characteristic curves (AUC)>0.7, while other scoring systems showed poor
      discrimination. However, the AUCs of each score were not significantly different
      from the MELD score AUC. CONCLUSION: The MELD score most correlated with total
      bilirubin after LDLT, while the APACHE II and SOFA scores seemed to correlate
      with mortality after LDLT.

PMID- 22410026
TI  - Pretransplant Model for End-stage Liver Disease score has no impact on
      posttransplant survival in living donor liver transplantation.
AB  - BACKGROUND: A high Model For End-stage Liver Disease (MELD) score>=25 has been
      reported to be associated with increased posttransplant mortality and morbidity
      among patients undergoing living donor liver transplantation (LDLT). We reviewed
      the results of patients undergoing LDLT at our transplant center for
      decompensated cirrhosis to determine whether a high MELD impacted posttransplant
      survival. METHODS: From April 2002 to May 2011, 86-176 patients (49%) who
      underwent LDLT at our center had the indication of decompensated cirrhosis
      without hepatocellular carcinoma. Data were expressed in mean values+/-standard
      error of the means (range). Patients survival rates were analyzed using Kaplan
      Meier method. RESULTS: Among the 86 patients with decompensated cirrhosis: Age
      was 49+/-2 (1-68) years and 60 (70%) were of male gender. The causes in 25 (29%)
      were hepatitis B and 25 (29%) hepatitis C as well as one each for hepatitis B/C
      and B/D coinfections: 9 (10%), alcoholic cirrhosis. MELD score was 18+/-1
      (range=6-40). In hospital mortality was 6/86 (7%). At 1152+/-95 (range=7-3317)
      days posttransplant follow-up 64 (74%) were alive with 1-, 3-, and 5-year
      survival rates of 84%, 70%, and 70%, respectively. MELD scores did not differ
      between those who survived and those who died (17.5+/-8.0 versus 17.8+/-8.4). No
      difference was noted in those with MELD<25 or >=25. In fact, the recipient with
      the highest MELD score (40) survived. CONCLUSION: A high MELD score had no impact
      on posttransplant survival among cirrhotic patients undergoing LDLT. It should be
      considered to be an urgent indication rather than a contraindication to LDLT.

PMID- 22410027
TI  - Extended criteria for living donor liver transplantation in patients with
      advanced hepatocellular carcinoma.
AB  - BACKGROUND: The purpose of this study was to evaluate the possibility of
      expanding the selection criteria in living donor liver transplantation (LDLT) to
      treat hepatocellular carcinoma (HCC). METHODS: From October 2000 to December
      2010, we retrospectively analyzed 71 patients who had undergone LDLT beyond the
      Milan criteria (MC), among the entire cohort of 199 HCC patients. We evaluated
      the tumor biology as well as overall and disease-free survival (DFS), seeking to
      identify risk factors for recurrence. The median follow-up was 37 months (range 5
      124). RESULTS: Among the 71 patients beyond the MC were 18 recurrences and 30
      deaths. Their 5-year overall and DFS rates were 52.3% and 67.7%, respectively. On
      multivariate analysis, tumor diameter, tumor number, and E-S grade significantly
      influenced overall and DFS. According to our new criteria (size<=7 cm,
      number<=7), 86% of our patients would be included compared with 64% using MC.
      Five-year DFS and overall survival rates according to our criteria were
      comparable with the MC: 86.8% and 72.3% versus 86.8% and 73.4%, respectively.
      CONCLUSION: Our criteria appear to achieve useful cut-off values beyond the MC.

PMID- 22410028
TI  - Effectiveness of locoregional therapy before living donor liver transplantation
      in patients with hepatocellular carcinoma who meet the Milan criteria.
AB  - BACKGROUND: Many patients are diagnosed with hepatocellular carcinoma (HCC)
      within the Milan criteria. In Korea, these patients are preferentially treated
      with locoregional therapy (LRT) instead of living donor liver transplantation. We
      investigated the effectiveness of LRT in liver transplant recipients who met the
      Milan criteria at the time of HCC diagnosis and investigated risk factors for HCC
      recurrence. METHODS: We retrospectively reviewed the medical records of patients
      diagnosed with HCC who met the Milan criteria between 2002 and 2008. RESULTS: We
      performed 101 liver transplants for HCC during the study period. Seventy-one
      patients (70%) underwent pretransplant LRT. The disease-free survival rates at 1,
      3, and 5 years in patients who received LRT were 96.6%, 93.1%, and 93.1%, and in
      those who did not receive LRT, 94.2%, 83.4%, and 83.4%, respectively. There were
      no differences between the 2 groups. Multivariate analysis showed that a low
      Model for End-Stage Liver Disease (MELD) score and microvascular invasion were
      independent predictors of HCC recurrence after transplantation. The MELD scores
      and rate of microvascular invasion were not statistically different in patients
      with or without previous LRT. CONCLUSION: Pretransplant LRT for patients with HCC
      who met the Milan criteria at the time of diagnosis did not provide a clear
      benefit with respect to HCC recurrence after transplantation. If patients have
      suitable living donors, those who meet the Milan criteria should undergo a liver
      transplantation as soon as possible.

PMID- 22410029
TI  - Investigation of histological vascular invasion from preoperative evaluation in
      patients with hepatocellular carcinoma who underwent living donor liver
      transplantation.
AB  - Tumor vascular invasion is one of the worst factors of metastasis and/or
      recurrence in hepatocellular carcinoma (HCC) patients after living donor liver
      transplantation (LDLT), leading to poor outcomes. We investigated the relevance
      between preoperative parameters and histological vascular invasion among HCC
      patients who underwent LDLT. We enrolled 27 HCC patients who underwent LDLT from
      September 2003 to February 2011 in our hospital. Their primary diseases were
      hepatitis C (n=16) hepatitis B (n=9), primary biliary cirrhosis (n=1), and
      cryptogenic liver cirrhosis (n=1). The 2 groups were positive (N=7) versus
      negative (N=20) histological vascular invasion. We compared the greatest size and
      numbers of tumors from preoperative enhanced computerized axial tomography (CAT)
      scans, preoperative serum levels of alpha-fetoprotein (AFP) and protein induced
      by vitamin K absence or antagonist-II (PIVKA-II), as well as preoperative
      anticancer therapy. The preoperative greatest average diameter and numbers of
      tumor were 2.99 cm and 2.43, respectively, among positive patients, and 1.93 cm
      and 1.3, respectively, among patients with negative vascular invasion. The mean
      values of AFP and PIVKA-II were 3568.7 ng/mL and 2511.7 mAU/mL, respectively,
      among positive patients, and 812.8 ng/mL and 134.8 mAU/mL, respectively, among
      patients with negative vascular invasion. Five positive and 11 negative patients
      received preoperative anticancer therapy. Even if the tumor was within Milan
      criteria, namely, maximum size 3 cm and number of tumors 3, preoperative
      treatment may be a preoperative predictive factor for positive histological
      vascular invasion.

PMID- 22410030
TI  - Hepatocellular carcinoma downstaging in liver transplantation.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the leading malignant tumor in
      Taiwan. The majority of HCC patients are diagnosed in late stages and therefore
      in eligible for potentially curative treatments. Locoregional therapy has been
      advocated as an effective treatment for patients with advanced HCCs. PURPOSE: The
      aim of this study was to evaluate the outcomes of HCC downstaged patients after
      locoregional therapy to allow eligibility for liver transplantation. METHODS AND
      MATERIALS: From January 2004 to June 2010, 161 patients with HCCs underwent liver
      transplantation including 51 (31.6%) who exceeded the University of California
      San Francisco (UCSF) who had undergone successful locoregional therapy to be
      downstaged within these criteria. Among the downstaged patients, 48 (94.1%)
      underwent transarterial embolization; 7 (13.8%), percutaneous ethanol injection;
      24 (47.1%), radiofrequency ablation; 15 (29.4%), surgical resection, and 34
      (66.7%), combined treatment. RESULTS: The overall 1- and 5-year survival rates of
      all HCC patients (n=161) were 93.2% and 80.5%. The overall 1- and 5-year survival
      rates of downstaged (n=51) versus non-downstaged (n=110) subjects were 94.1%
      versus 83.7% and 92.7% versus 78.9%, respectively (P=.727). There are 15 (9.2%)
      HCC recurrences. The overall 1- and 5-year tumor-free rates of all HCC patients
      were 94.8% and 87.2%. The overall 1- and 5-year tumor-free rates between
      downstaged versus non-downstaged patients were 93.9% and 90.1% versus 95.2% and
      86.0%, respectively (P=.812). CONCLUSION: Patients with advanced HCC exceeding
      the UCSF/Milan criteria can be downstaged to fit the criteria using locoregional
      therapy. Importantly, successfully downstaged patients who are transplanted show
      excellent tumor-free and overall survival rates, similar to fit-criteria group.

PMID- 22410031
TI  - Clinical value of preoperative coronary risk assessment by computed tomographic
      arteriography prior to adult living donor liver transplantation.
AB  - PURPOSE: Patients with advanced liver diseases are at increased risk of
      cardiovascular events, resulting in a higher incidence of cardiac complications
      following liver transplantation (OLT). We assessed the clinical value of computed
      tomographic coronary arteriography (CTCAG) as a routine preoperative cardiac
      evaluation test in adult patients scheduled for living donor OLT (LDLT). METHODS:
      This single-center, prospective, observational study evaluated 247 adult patients
      being assessed for LDLT from April 2010 to March 2011. CTCAG was performed in
      patients with all-negative findings on routine cardiac workup, including thallium
      single photon emission computed tomography (SPECT). RESULTS: Of the 247 patients
      evaluated, 27 (10.9%) showed abnormal findings on CTCAG, with 18 (7.3%) showing
      mild to moderate involvement of one vessel; 7 (2.8%), two-vessel; and 2 (0.8%),
      three-vessel involvement. Coronary artery calcification was identified in
      patients with significant coronary artery stenosis. No adverse events occurred
      after CTCAG. Noticeable hypotensive episodes during LDLT surgery occurred in 5%
      of patients, mostly related to massive bleeding or postperfusion syndrome. During
      the first 3 months after LDLT, 3% of patients showed stress cardiomyopathy, but
      all recovered with supportive care. CONCLUSIONS: The poor general medical
      condition of LDLT candidates and the diagnostic accuracy of CTCAG suggest that
      this test should be included in the routine pretransplant cardiac workup, along
      with thallium SPECT, for these patients.

PMID- 22410032
TI  - Does lymphocyte cross-matching predict acute rejection and graft survival in
      liver transplantation?
AB  - INTRODUCTION: The role of lymphocyte cross-matches (LCM) remains controversial in
      the liver transplant field. The aim of this study was to correlate the risk for
      acute rejection episodes and graft survival in liver transplantation with
      pretransplant LCM results. PATIENTS AND METHODS: We enrolled 184 adult liver
      transplantation patients, excluding pediatric and second grafts. The 129 living
      donor and 55 deceased donor liver transplantations were divided into 2 groups:
      LCM (+); (n=20) and LCM (-); (n=164). RESULTS: There were no differences in the
      demographic features, such as gender and recipient age, original disease, Model
      for End-Stage Liver Disease score, donor type, number of human leukocyte antigen
      mismatches, and cold ischemia times. There were no hyperacute rejection episodes
      in the LCM (+) group. Also, posttransplant complications such as acute rejection
      episode, biliary complication, or hepatic artery thrombosis were not different.
      Acute rejection episodes occurred in 5.0% of the LCM (+) group and 15.2% of the
      LCM (-) group (P=.317). Bile duct complications after transplantation arose in
      20.0% of the LCM (+) group and in 32.9% of the LCM (-) group (P=.312). The 2
      groups showed no difference in graft survival rate analyzed by the Kaplan-Meier
      method according to LCM results. CONCLUSION: Pretransplant LCM results were not
      associated with overall graft survival or acute rejection episodes in this study.

PMID- 22410033
TI  - Conscious recovery response in post-hepatic transplant as a function of time
      related acute hepatic encephalopathy.
AB  - BACKGROUND: H Coma due to acute hepatic failure produces a high mortality rate
      with rapid progression of cerebral edema and brain herniation. Early
      transplantation increases survival of patients with acute hepatic encephalopathy.
      In previous studies, scant attention has focused on the conscious recovery time
      after living donor liver transplantation (ldlt) and whether the conscious
      recovery time was directly proportional to the length of coma before
      transplantation. PATIENTS AND METHODS: We have reported herein three adult
      patients with decompensated chronic end-stage liver disease who underwent right
      lobe LDLT. Their general conditions had markedly deteriorated; two patients
      displayed massive ascites. All three subjects displayed grade IV encephalopathy
      with endotracheal intubation and intensive care management. Their biochemical
      data revealed hyperammonemia, marked cholestasis, and coagulopathy. RESULTS:
      After LDLT the patients recovered from coma at a mean time similar to that in
      coma. Preoperatively the patients exhibited acute deep coma with respiratory
      failure on preoperative days 5, 3, and 1 with consciousness regained on
      postoperative day 5, 3 and 1, respectively. CONCLUSION: We suggest that patients
      with acute deep coma (grade IV), who were formerly regarded as irreversible,
      benefit with LDLT, preventing worsening of complications, and that shows a time
      dependent recovery the pretransplant comatose status.

PMID- 22410034
TI  - Cardiac output derived from arterial pressure waveform analysis in patients
      undergoing liver transplantation: validity of a third-generation device.
AB  - BACKGROUND: Hemodynamic monitoring is essential to a successful liver
      transplantation procedure. FloTrac, a hemodynamic monitor that uses arterial
      waveform-based pulse contour analysis for cardiac output (CO) measurement, has
      proven useful in many clinical settings. One of the primary foci of FloTrac's
      recent third-generation software upgrade was improving its accuracy in low
      systemic vascular resistance status. We evaluated the accuracy of the upgraded
      FloTrac monitor during liver transplantation. MATERIALS AND METHODS: Twenty-eight
      patients undergoing liver transplantation were enrolled in the study. Two sets of
      CO were measured with a radial arterial line connected to a FloTrac monitor
      (COFT) and a pulmonary artery catheter connected to a continuous cardiac output
      Vigilence monitor (COPAC). Simultaneous CO measurement was performed and recorded
      every 5 minutes throughout the surgery. Bland-Altman analysis was used to
      estimate the accuracy. The comparative method and reference method were
      considered interchangeable if the limits of agreement did not exceed a threshold
      set a priori at the greater of +/-1 L/min, or a percentage error of lesser than
      30%. RESULTS: In all, 3234 paired data were collected. The bias was -0.8 L/min
      and the limits of agreements were -5.6 to 4.0 L/min. Percentage error was 75%.
      Regression analysis of the systemic vascular resistance index (SVRI) and the bias
      between COPAC and COFT showed that the bias was inversely related to the SVRI
      [r2=0.49; P<.001, y=-32.1983+9.9978 Log(x)]. CONCLUSIONS: Despite a software
      upgrade, the effectiveness of the FloTrac artery-derived cardiac output monitor
      for CO measurement during liver transplantation remains limited.

PMID- 22410035
TI  - Stroke volume variation derived by arterial pulse contour analysis is a good
      indicator for preload estimation during liver transplantation.
AB  - BACKGROUND: Accurate determination of preload during liver transplantation is
      essential. Continuous right ventricular end diastolic volume index (RVEDVI) has
      been shown to be a better preload indicator during liver transplantation than the
      filling pressures. However, recent evidence has shown that dynamic variables, in
      this case stroke volume variation (SVV), are also good indicators of preload
      responsiveness. In this study, we evaluated the correlation between SVV, which we
      derived from arterial pulse contour analysis and RVEDVI. METHODS: In this study,
      we looked for possible relationships between SVV obtained through FloTrac/Vigileo
      monitor, central venous pressure (CVP), pulmonary arterial occlusion pressure
      (PAOP), and RVEDVI in 30 patients undergoing liver transplantation. Measurements
      were taken at 11 defined points during different phases across liver
      transplantation. Each set of measurement was taken during a steady state, which
      means at least 15 minutes elpased after any changes occured in either the
      infusion rate of catecholamines or ventilator settings. Pearson's test was used
      for correlation estimation. RESULTS: There was a statistically significant
      (P<.01) relationship between SVV and RVEDVI with a correlation coefficient of 
      0.87. The correlations between CVP (r=0.42), PAOA (r=0.46), and RVEDVI were less
      strong. CONCLUSION: We conclude that SVV is a good indicator for preload
      estimation during liver transplantation. A higher SVV value is associated with a
      more hypovolemic fluid status.

PMID- 22410036
TI  - Cardiac output derived from arterial pressure waveform analysis: validation of
      the third-generation software in patients undergoing orthotopic liver
      transplantation.
AB  - BACKGROUND: The upgraded third-generation software (version 3.02) for the
      FloTrac/Vigileo system has been developed to particularly improve the accuracy of
      cardiac output (CO) measurements in hyperdynamic conditions. The aim of our study
      was to compare the CO values obtained using the FloTrac/Vigileo system during
      orthotopic liver transplantation (OLT) with those obtained in the same
      circumstances using a Swan-Ganz catheter (bolus thermodilution method). METHODS:
      Twenty consecutive recipients scheduled for OLT were studied. Simultaneous CO
      values measured by both devices were obtained at 10 predefined time points
      throughout the surgery. A percentage error of not more than 30% was established
      as the criterion for device interchangeability. RESULTS: A total of 200 paired
      measurements were obtained. The CO values derived from the FloTrac/Viligeo ranged
      from 2.8 to 10.9 L/min, with a mean of 5.91+/-1.81 L/min. The values from bolus
      thermodilution ranged from 2.2 to 13.2 L/min, with a mean of 6.12+/-2.07 L/min.
      The bias was 0.22, and the limits of agreement were -3.13 to 3.56 L/min. The
      percentage error between the FloTrac/Viligeo and bolus thermodilution
      measurements was 54.93%. The percentage errors of paired measurements in three
      surgical phases by subgroup analysis were 43.50% (dissecting phase), 62.9%
      (anhepatic phase), and 56.05% (reperfusion phase), respectively. CONCLUSION: CO
      measurements obtained using the less invasive arterial waveform FloTrac/Vigileo
      system upgraded with the third-generation software had poor intraoperative
      agreement with pulmonary artery thermodilution CO measurements in patients
      undergoing OLT.

PMID- 22410037
TI  - Tying a slipknot to an intubation stylet for facilitating insertion of a
      nasogastric tube in liver transplant recipients: a prospective, randomized study.
AB  - BACKGROUND: It is sometimes difficult and harmful to insert a nasogastric tube
      (NGT) into a patient with a tendency to bleed and anesthetized recipient of liver
      transplantation. As a "Rusch" intubation stylet tied by a slipknot, Highwayman's
      hitch, to the NGT, it is easy to introduce the NGT through nasal cavity and
      oropharyngeal space. We designed this study to evaluate the usage of this novel
      method in the guidance of NGT insertion in liver transplant recipients. METHODS:
      Eighty recipients were randomly allocated to both groups. In the control group
      (group C), the NGT was inserted with the patient's head in neutral position. In
      the stylet group (group S), the NGT was inserted with the assistance of a Rusch
      intubation stylet tied together at the tips. The success rates, duration of
      insertions, and occurrences of complications were recorded. All of the failed
      cases in group C and the rescue success rate with the new technique were also
      evaluated. RESULTS: Successful insertions were recorded in 38/40 patients (95%)
      in group S and in 27/40 patients (67.5%) in group C, and the difference was
      statistically significant. The incidences of kinked NGT were 17.5% in group C and
      2.5% in group S, respectively, and the difference was statistically significant.
      The rates of nasal mucosal bleeding were 22.5% in group C and 25% in group S. The
      rescue success rate of 13 failure cases in the group C was 84.6%. CONCLUSION: The
      intubation stylet-guided method is reliable, with high success rate of NGT
      insertion in patients with a tendency to bleed anesthetized recipients of liver
      transplantation.

PMID- 22410038
TI  - The effects of desflurane and isoflurane on hepatic and renal functions after
      right hepatectomy in living donors.
AB  - PURPOSE: Considering the severe nature of living donor right hepatectomy (removal
      of two thirds of the original liver), identification of an anesthetic agent
      having a minimal impact on postoperative organ function seems important. We
      compared postoperative hepatic and renal functions between 2 inhalational
      anesthetics, desflurane (Des) and isoflurane (Iso) among living donors undergoing
      right hepatectomy. METHOD: Sixty-four adult donors included in this retrospective
      study were divided into a Des group (n=32) and an Iso group (n=32). Before the
      induction of anesthesia, morphine sulfate (400 MUg) was injected intrathecally.
      Anesthesia was maintained with 1 minimum alveolar concentration (MAC) of Des or
      Iso plus intravenous remifentanil. Hepatic and renal function tests were analyzed
      preoperatively, immediately after operation, and on the first, second, third,
      fifth, seventh, and thirtieth postoperative days (POD). RESULTS: Total bilirubin
      showed significant elevations on POD 1, 5, 7, and 30 in the Des group. Estimated
      glomerular filtration rate was significantly lower immediately after operation
      and on POD 1 in the Des group. The postoperative complication rates were similar
      between the 2 groups, and no patient developed hepatic or renal failure.
      CONCLUSION: The present study showed better postoperative hepatic and renal
      function tests with Iso than Des at an equivalent dose of 1 MAC among living
      donors undergoing right hepatectomy.

PMID- 22410039
TI  - The relationship between postoperative intravenous patient-controlled fentanyl
      analgesic requirements and severity of liver disease.
AB  - PURPOSE: Decreased inhalational anesthetic requirements during orthotopic liver
      transplantation (OLT) have been reported according to the severity of the pre
      existent disease as well as decreased opioid requirements thereafter. The aim of
      the present study was to determine the relationship between postoperative opioid
      requirements and severity of liver disease among OLT patients. METHODS: We
      retrospectively reviewed 44 recipients who used intravenous fentanyl-based
      patient-controlled analgesia (PCA) after OLT from November 2009 to May 2010. The
      severity of liver disease was assessed using the model for end-stage liver
      disease (MELD) score. Recipients were divided into a low-MELD group (<20; n=30)
      and a high-MELD group (>=20; n=14). The amounts of PCA infusion and rescue opioid
      up to 3 postoperative days (POD) were compared between the 2 groups. The
      intensity of pain at rest and when coughing was assessed using visual analog
      scale (VAS) scores. RESULTS: The cumulative opioid requirements via PCA on POD 1,
      2, and 3 were significantly lower in the high-MELD than the low-MELD group. The
      amounts of rescue opioid were similar between the 2 groups. However, the
      intensity of pain at both rest and when coughing on POD 1, 2, and 3 were
      significantly less severe in the high-MELD than the low-MELD group. CONCLUSIONS:
      OLT patients with high MELD scores required less postoperative opioids and
      experienced less pain than those with low scores. Therefore, postoperative pain
      control after OLT should be carefully titrated according to the severity of the
      liver disease.

PMID- 22410040
TI  - Hepatic artery reconstruction in living donor liver transplantation: running
      suture under surgical loupes by cardiovascular surgeons in 180 recipients.
AB  - OBJECTIVES: The aim of our study was to retrospectively investigate the outcomes
      of hepatic artery (HA) reconstruction by cardiovascular surgeons in adult-to
      adult living donor liver transplantation (A-A LDLT). METHODS: From April 2007 to
      April 2011, 187 recipients underwent A-A LDLT. After excluding seven ABO
      incompatible transplant recipients, we reviewed the courses of 180 patients
      including 125 men and 55 women of mean age 52.5+/-9.2 years (range=23-71). One
      hundred seventy-seven patients received right-lobe grafts with inclusion of
      middle hepatic vein (MHV); two, right-lobe grafts without MHV; and one, left-lobe
      graft. A continuous, single-stitch, running suture with the parachute technique
      was used for HA reconstruction. The anastomosis was performed by cardiovascular
      surgeons employing surgical loupes with 4.5* magnification. RESULTS: The mean
      time for an arterial reconstruction was 10.7+/-4.0 minutes (median=10, range=4
      30). Hepatic arterial thrombosis (HAT) was encountered in 3 (1.66%) patients. One
      HAT that developed on postoperative day 1 was successfully rescued by the intra
      arterial infusion of urokinase. Another patient required reoperation due to a
      redundant kinked HA. A third HAT patient underwent successful retransplantation
      with a cadaveric graft on postoperative day 6. In our series, no delayed HAT was
      detected and no recipient deaths were related to HAT. CONCLUSION: HA
      reconstruction with a running suture under surgical loupes is a feasible
      technique in A-A LDLT. A speedy reconstruction can be performed by an experienced
      cardiovascular surgeon with a low incidence of HAT.

PMID- 22410041
TI  - Right gastroepiploic artery is the first alternative inflow source for hepatic
      arterial reconstruction in living donor liver transplantation.
AB  - BACKGROUND: Sufficient arterial flow after living donor liver transplantation
      (LDLT) is closely related to graft survival and prevention of postoperative
      complications. However, some unfavorable hepatic arterial conditions in
      recipients preclude reconstruction, requiring alternative stumps. We have used
      the right gastroepiploic artery (RGEA) as a first alternative for hepatic inflow.
      METHODS: From January 2006 to December 2008, we performed 754 LDLTs including 28
      cases of RGEA among hepatic arterial anastomoses. The arterial anastomosis was
      performed by an single surgeon under 859 a microscope using an end-to-end
      interrupted suture technique. RGEA was mobilized over 15 cm from the greater
      curvature of stomach and greater omentum. RESULTS: The indications for RGEA use
      included severe hepatic arterial injury from previous transarterial
      chemoembolization (n=14), need for additional arterial flow in dual-grafts LDLT
      (n=13), poor blood flow from the recipient hepatic artery (n=3), and arterial
      injury during hilar dissection (n=3). The mean diameter of the isolated RGEA was
      2.0+/-0.2 mm (range: 1.0-2.5). Most hepatic arterial anastomoses were performed
      with a significant size discrepancy of more than twofold. All reconstructed
      hepatic arterial flowes showed good; no complication was identified during the
      mean follow-up period of 56 months to date. CONCLUSIONS: Using RGEA as an
      alternative arterial inflow is a simple, reliable procedure for situations of
      inadequate recipient hepatic or multiple graft arteries.

PMID- 22410042
TI  - Long-term outcomes of portal Y-graft interposition for anomalous right portal
      veins in living donor liver transplantation.
AB  - BACKGROUND: Anomalous portal vein (PV) branching in living donor livers is not
      uncommon and usually leads to double PV orifices of the right lobe grafts. We
      have assessed the long-term outcomes of portal Y-graft interposition for adult
      living donor liver transplantation (LDLT). METHODS: We retrospectively assessed
      the outcomes of 79 right-lobe LDLTs using portal Y-graft interposition among the
      2001 adult LDLTs performed at our institution from January 2002 to December 2010.
      RESULTS: Donor PV types were type III except for one case of type II. Sources of
      Y-grafts were recipient autologous PV in 76 LDLTs, fresh iliac vein allografts in
      two, and patch plasty using recipient greater saphenous vein in one. Detailed
      procedures included a portal Y-graft resection with Y-limbs, corner stay sutures,
      tying of suture materials under direct mechanical dilatation, and direct edge-to
      edge anastomosis to the recipient remnant main PV. Early PV stenting was
      necessary in five patients (6.3%) due to stenosis or buckling deformity. During a
      mean follow-up of 42 months, all PVs remained patent until patient death or
      censoring. Overall 1-, 3-, and 5-year patient survival rates were 93.6%, 88.3%,
      and 85.5%, respectively. None of the 79 donors experienced major complications
      requiring reoperation or therapeutic intervention. CONCLUSIONS: Due to their
      technical feasibility and excellent long-term outcome, portal Y-graft
      interposition should be considered a standard procedure for reconstruction of
      right-lobe grafts with double PV orifices.

PMID- 22410043
TI  - Standardization of modified right lobe grafts to minimize vascular outflow
      complications for adult living donor liver transplantation.
AB  - BACKGROUND: After >2000 adult living donor liver transplants (LDLTs), we observed
      minimization of the complication rate using case-by-case modification of venous
      outflow reconstruction in right liver graft (RLG), standardization seeking intend
      to provide a hemodynamic- based, regeneration-compliant hepatic outflow
      reconstruction. METHODS: We retrospectively examined 100 consecutive adult LDLT
      using modified RLG before and after application of RLG standardization to compare
      the 6-month incidences of vascular outflow complications. RESULT: The right
      hepatic vein stenting rate for first 6 months was 5% in the customized group and
      1% in the standardized group (P=.212). The middle hepatic vein stenting rate for
      first 6 months was 9% in the customized group and 4% in the standardized group
      (P=.373). The inferior right hepatic vein stenting rate for first 6 months was
      12.8% in the customized group and 7.1% in the standardized group (P=.472). The
      overall 6-month patient survival rate was 94% in the customized group and 95% in
      the standardized group (P=.867). The overall incidence of significant RLG venous
      outflow complications was 19% in the customized group and 8% in the standardized
      group (P=.023). CONCLUSION: Standardization as a universal graft model seemed to
      be more effective and feasible than conventional graft customization requiring
      individualized case-by-case modification.

PMID- 22410044
TI  - Living donor right hepatectomy with inclusion of the middle hepatic vein: outcome
      in 200 donors.
AB  - Venous congestion of segments V and VIII of the graft is observed frequently in
      right-lobe living donor liver transplants (LDLT) without middle hepatic vein
      (MHV) drainage. It can cause graft dysfunction and failure. Inclusion of the MHV
      in the right lobe graft allows optimal venous drainage but can pose adverse
      effects for the donor. From May 2005 to April 2011, we performed 202 right-lobe
      LDLTs using grafts that all (except two) contained the MHV. The mean duration of
      donor surgery was 558+/-132 minutes (median 540, range 332-1100), and estimated
      blood loss 441+/-309 mL (median 350, range 35-3200). No donor was admitted to the
      intensive care unit postoperatively. The mean hospital stay was 8.7+/-2.1 days
      (median 8, range 6-22). Postoperatively, 39 donors (19.5%) experienced Clavien
      grade I and II complications, mostly minor wound infections or massive ascites
      necessitating diuretic therapy. Seven (3.5%) donors displayed Clavien grade III
      complications, including five bile leakages requiring endoscopic retrograde
      biliary drainage and two abdominal wound dehiscences requiring repair under
      general anesthesia. There was no donor death. In conclusion, inclusion of the MHV
      in a right-lobe LDLT was safe for most donors.

PMID- 22410045
TI  - Anatomic similarity of the hepatic artery and portal vein according to the donor
      recipient relationship.
AB  - INTRODUCTION: Anatomic variants of the hepatic vasculature are common, so precise
      preoperative donor evaluation, including variations in the vasculature, is
      essential. We analyzed the anatomic similarity according to the donor-recipient
      relationship. METHODS: Among the cases who underwent living donor liver
      transplantations from September 2008 to January 2011 we selected 104 cases with
      clearly defined hepatic artery and portal vein on preoperative computed
      tomography. They were classified according to Hiatt et al for the hepatic artery
      and Cheng for the portal vein. We categorized the 104 cases into three groups:
      parents-child (n=40), sibling (n=24) and no-relation (n=40), for analysis of the
      concordance of the hepatic artery and portal vein. RESULT: Anatomic variations
      were observed in 25% of donors and 23.1% of recipients in the hepatic artery and
      6.7% of donors and 10.6% of recipients in the portal vein. There was no
      significant difference in the distribution of the type of hepatic vasculature.
      Identical anatomic variations between donors and recipients were observed in
      62.5% of the parent-child; 66.7% of the sibling and 52.5% of no-related group
      (P=.493) in the hepatic artery and 92.5%, 100%, and 77.5% (P=.014) in the portal
      vein respectively. CONCLUSION: There was no similarity in the anatomic variations
      of the hepatic artery according to the donor-recipient relationship, but a
      similarity in portal venous anatomy according to the donor-recipient
      relationship.

PMID- 22410046
TI  - Is microsurgical technique useful in biliary reconstruction of living donor liver
      transplantation?
AB  - INTRODUCTION: Biliary reconstruction remains the "Achilles' heel" of living donor
      liver transplantation (LDLT). In the last decades, the technical aspects of
      biliary reconstruction have been debated for their impact on biliary
      complications in LDLT. A microsurgical technique in biliary reconstruction is
      more attractive. PATIENTS AND METHODS: From December 2010 to June 2011, 15
      primary LDLTs underwent duct-to-duct biliary reconstruction using a microscopic
      technique. External stents were inserted in all patients. All procedures were
      performed under a microscope by a single transplant microsurgeon. RESULTS: The
      time consumed for bile duct reconstruction using the microscopic technique was 35
      minutes. There were 8 grafts with a single bile duct orifice and seven with two
      orifices. The average duct size was 3 mm in patients with two orifices and 5 mm
      in those with a single orifice. There was no bile leak or biliary stricture
      associated with the biliary reconstruction over a median 5-month follow-up. There
      were two cases of bile leakage from the cut hepatic surface. CONCLUSION: The
      microscopic technique reduced early biliary complications. However, further
      technical advances are needed to decrease the time consumptions for the
      procedure.

PMID- 22410047
TI  - Living donor liver transplantation in children with cholestatic liver disease: a
      single-center experience.
AB  - OBJECTIVES: Cholestatic liver disease (CLD) is the main indication for liver
      transplantation in children. This retrospective study evaluated the outcomes of
      living donor liver transplantation (LDLT) in children with CLD. METHODS: One
      hundred fifty-nine children with CLD who underwent 164 LDLT between May 2001 and
      May 2011 were evaluated. Their original diseases were biliary atresia (n=145,
      91%), Alagille syndrome (n=8, 5%), primary sclerosing cholangitis (n=2), and the
      others (n=4). The mean age and body weight of the recipients at LDLT was 42+/-53
      months and 14.0+/-11.0 kg, respectively. RESULTS: Parents were living donors in
      98%. The left lateral segment was the most common type of graft (77%). There were
      no reoperations and no mortality in any living donor. Recipients' postoperative
      surgical complications consisted mainly of hepatic arterial problems (7%),
      hepatic vein stenosis (5%), portal vein stenosis (13%), biliary stricture (18%),
      intestinal perforation (3%). The overall rejection rate was 31%. Cytomegalovirus
      infection and Epstein-Barr virus disease were observed in 26% and 5%,
      respectively. Retransplantation was performed five times in four patients; the
      main cause was hepatic vein stenosis (n=3). Four patients died; the main cause
      was gastrointestinal perforation (n=2). The body height of Alagille syndrome
      patients less than 2 years old significantly improved compared with older
      patients after LDLT. The 1-, 5-, and 10-year patient survival rates were 98%,
      97%, and 97%, respectively. CONCLUSIONS: LDLT for CLD is an effective treatment
      with excellent long-term outcomes.

PMID- 22410048
TI  - Hemodynamic changes during the anhepatic phase in pediatric patient with biliary
      atresia versus glycogen storage disease undergoing living donor liver
      transplantation.
AB  - OBJECTIVE: The aim of this study was to compare the hemodynamic changes caused by
      clamping of the inferior vena cava and portal vein in biliary atresia (BA) versus
      glycogen storage disease (GSD) patients undergoing living-donor liver
      transplantation (LDLT) without venovenous bypass. METHODS: We reviewed
      retrospectively the anesthesia charts of pediatric LDLT patients. Age, weight,
      height, blood loss, blood product use and fluid replacement between groups were
      compared with Mann-Whitney test, and systolic blood pressure (SBP), heart rate
      (HR), central venous pressure (CVP) before clamping of the inferior vena cava,
      and 4 measurements during anhepatic phase and 5 minutes after reperfusion were
      compared with analysis of variance. RESULTS: One hundred four BA patients (GI)
      and 12 GSD patients (GII) showed mean total blood loss among GI to be more than
      among GII, but the blood products and crystalloids infused during the operation
      were not significantly different. The changes of SBP, HR, and CVP after clamping
      of the IVC were significantly different between groups. CVP of GII was lower than
      GI, indicating that venous return among GII was more affected, subsequently
      showing lower SBP and higher HR. CONCLUSIONS: Total clamping of the inferior vena
      cava resulted a greater decrease in CVP in GII with subsequently lower SBP and
      faster HR compared with GI.

PMID- 22410049
TI  - Biliary complications and management in pediatric living donor liver
      transplantation for underlying biliary atresia.
AB  - BACKGROUND: Biliary complications are a major problem in pediatric liver
      transplantation. The aim of this study was to evaluate the management and
      outcomes of biliary complication after pediatric living donor liver
      transplantation (LDLT). METHODS: From 1994 to 2010, 157 pediatric LDLT due to
      biliary atresia were performed in our center. Doppler ultrasound was initially
      performed daily for 2 weeks postoperatively to evaluate biliary and vascular
      complications. Computed tomography and or magnetic resonance cholangiography were
      performed when complications were suspected. They were treated using radiological
      or surgical interventions. RESULTS: Among the 157 cases, we observed 10 (6.3%)
      biliary complications, which were divided into three groups: bile leakage (n=3);
      biliary stricture without vascular complication (n=4); and biliary stricture with
      vascular complication (n=3). The three cases bile leakages recovered after
      interventional procedures. The seven biliary strictures underwent percutaneous
      transhepatic cholangial drainage (PTCD). All cases without vascular complications
      were completely cured after PTCD or a subsequent surgical re-anastomosis. In the
      vascular complication group, early recorrection of the HA occlusion with
      successful PTCD treatment were performed in two cases, but one other case with
      diffuse ischemic biliary destruction had a poor result. CONCLUSION: Successful
      interventional radiographic approaches are effective for anastomotic biliary
      complications but with poor results in diffuse ischemic biliary destruction.

PMID- 22410050
TI  - Liver transplantation for Wilson's disease in pediatric patients: decision making
      and timing.
AB  - Transplantation for Wilson's disease occupies 1/3 of the cases for metabolic
      diseases in Japan. At the end of 2009, 109 transplantations had been performed
      including three deceased donor cases in the Japanese registry. We herein discuss
      problems of transplantation for Wilson's disease as well as its indication,
      timing, and social care. We retrospectively reviewed four fulminant cases and two
      chronic cases who underwent living donor liver transplantation. There were two
      boys and two girls. Four adolescents of average age 11.3 years underwent living
      donor liver transplantation. Duration from onset to transplantation ranged from
      10 to 23 days. Average Model for End-stage Liver Disease (MELD) score was 27.8
      (range=24-31). All patients were administrated chelates prior to transplantation.
      MELD, New Wilson's index, Japanese scoring for liver transplantation, and liver
      atrophy were useful tools for transplantation decision making; however, none of
      them was an independent decisive tool. Clinical courses after transplantation
      were almost uneventful. One girl, however, developed an acute rejection episode
      due to noncompliance at 3 years after transplantation. All patients currently
      survive without a graft loss. No disease recurrence had been noted even using
      living related donors. Two adults evaluated for liver transplantation were listed
      for deceased donor liver transplantation. Both candidates developed cirrhosis
      despite long-term medical treatment. There were no appropriate living donors for
      them. There are many problems in transplantation for Wilson's disease. The
      indications for liver transplantation should be considered individually using
      some decision-making tools. The safety of the living donor should be paid the
      most attention.

PMID- 22410051
TI  - Hemodynamics of portal venous stenosis before and after treatment in pediatric
      liver transplantation: evaluation with Doppler ultrasound.
AB  - AIM: The aim of this study was to evaluate portal vein stenosis (PVS) in
      pediatric liver transplantation (PLT) using Doppler ultrasound (DUS) before and
      after interventional management for hemodynamic changes. MATERIALS AND METHODS:
      From 2000 to 2010, we encountered 11 PVS cases among 180 PLT that were evaluated
      using DUS and computed tomography (CT) angiography (CTA); all underwent portal
      stenting. DUS was used to monitor portal hemodynamics. For the diagnosis of PVS,
      we investigated multiple parameters including stenotic size (SS), stenotic ratio
      (SR) (SR [%]=PRE-SS/PRE [PRE=stenotic size]), portal flow velocity ratio (VR)
      (VR=VS/PRE [PRE=velocity at prestenotic site; VS=peak velocity at stenotic
      site]), spleen size, and platelet count. RESULTS: The incidence of PVS was 5.6%
      (11/180). The PV was 2.5 mm using DUS and 2.7 mm using CTA. The average SR was
      65% fitting the criterion. Low prestenotic portal flow<12 cm/sec and high peak
      velocity in the stenotic segment (up to 147 cm/sec) were observed in 6 cases. The
      VR value was high at 7.5:1 and there was splenomegaly with thrombocytopenia.
      After portal vein stenting, hyperperfusion occurred might after reopening the
      stenosis: the flow increased to an average of 34 cm/sec and then flow decreased
      slowly to a stable level 2 weeks later. The size of the spleen decreased from 17
      to 12 cm and the thrombocytopenia also improved with platelet counts increasing
      from 67*10(3) to 178*10(3)/MUl at 2 months follow-up. The changes in portal flow,
      portal vein size, spleen size, and platelet count were significant (P<.05).
      CONCLUSION: PVS is diagnosed using DUS by increased intrahepatic PV dilatation,
      peak flow at the stenotic site, discrepant VR. Early portal stenting showed a
      better prognosis. DUS is essential and effective for hemodynamic monitoring and
      management of PVS.

PMID- 22410052
TI  - Clinical experience of more than 200 cases of pediatric liver transplantation at
      a single center: improved patient survival.
AB  - The aim of this study was to present our experience with more than 200 cases of
      orthotopic liver transplantation (OLT) at a single center. We conducted a
      retrospective, single-center assessment of the demographic and clinical factors
      in children who underwent OLT from 1994 to 2010. Two hundred children younger
      than 18 years of age underwent 200 primary and 9 liver re-transplantations. The
      overall patient survival rates before 2003 at 1, 5, and 10 years were 86.4%,
      79.5%, and 78.4%, respectively; whereas after 2003 they were 95.4% and 95.4% at 1
      and 5 years, respectively (P<.05). Our center's results showed durable, improved
      outcomes in recent years.

PMID- 22410053
TI  - Primary versus salvage living donor liver transplantation for patients with
      hepatocellular carcinoma: impact of microvascular invasion on survival.
AB  - OBJECTIVE: Salvage liver transplantation (LT) has been proposed for patients with
      a small hepatocellular carcinoma (HCC) and preserved liver function. Few reports
      have been issued on salvage LT in a living-donor (LD) LT setting. Therefore, we
      performed this study to evaluate differences in tumor invasiveness and other risk
      factors on survival after salvage versus primary LDLT. METHODS: Between September
      1996 and December 2008, 324 patients with HCC underwent LT. We excluded 138
      patient from the analysis, leaving 186 HCC patients for analysis, including 17
      (9.1%) who had undergone earlier resection, the salvage LDLT cohort. The other
      169 patients underwent primary LDLT. RESULTS: Intrahepatic metastasis, Edmonson
      Steiner histologic grade, microscopic vascular invasion, and preoperative serum
      alpha-fetoprotein levels significantly influenced tumor recurrence. Microscopic
      vascular invasion, intrahepatic metastasis, Edmonson-Steiner histologic grade,
      and treatment by salvage LDLT were significantly associated with poor patient
      survival univariate analysis. However, only microscopic vascular invasion was
      significant on multivariate analysis. The treatment modality (primary or salvage
      LDLT) was not observed to affect overall or disease-free survival significantly
      on multivariate analysis. Disease-free survival was significantly better in the
      primary than in the salvage LDLT group. Furthermore, patients in the primary LDLT
      group tended to show better survival. However, when stratified by the presence or
      absence of microscopic vascular invasion, no significant group difference was
      found for overall or disease-free survival among those without versus with
      microscopic vascular invasion. CONCLUSIONS: Five-year overall survival after
      primary versus salvage LDLT were similar when differences in tumor pathologic
      features, such as microscopic vascular invasion, were taken into account.
      Multivariate analysis showed that the treatment itself was not a significant
      prognostic factor for survival.

PMID- 22410054
TI  - Newly defined clinical features and treatment experience of seventh day syndrome
      following living donor liver transplantation.
AB  - AIM: The aim of this study was to describe a unique Seventh-Day Syndrome (7DS) in
      our liver transplantation center. METHODS: We performed a retrospective analysis
      of 244 cases of adult living donor liver transplantations (LDLT) performed in our
      liver transplantation center from January 1995 to January 2009. RESULTS: Since
      2005, we identified 8 cases of 7DS. Previously reported features for 7DS include
      a rapid deterioration of liver function followed by renal failure and a sudden
      peak in liver enzyme levels around day 7. In addition, the following attributes
      have been observed in our patients: (1) all recipients were males while the
      donors included both genders; (2) most patients showed increased levels of
      irritability; (3) color Doppler revealed reduced blood flow or bidirectional
      blood flow in the portal vein; (4) coagulation necrosis was observed with
      disruption of lobular architecture and increased expression of death receptor Fas
      in all examined patients; (5) after onset, a steroid pulse with or without OKT3
      therapy showed minimal effect; (6) a abrupt increase in liver enzymes was noted 1
      2 days after intravenous (IV) methylprednisolone was switched to oral
      immunosuppressants; and (7) extension of IV methylprednisolone treatment delayed
      the occurrence from 8 to 11 days postoperatively. CONCLUSIONS: 7DS is a distinct
      entity associated with early graft dysfunction, which is associated with a high
      rate of mortality and need for retransplantation. Coagulation necrosis and Fas
      receptor activation may be implicated in the occurrence of 7DS. Our study
      supported the hypothesis that 7DS may be associated with an undefined immune
      response. Our experience extending IV methylprednisolone treatment seeking to
      delay occurrence and reduce mortality provided a possible therapeutic approach
      for 7DS.

PMID- 22410056
TI  - Recipient and perioperative risk factors associated with liver transplant graft
      outcomes.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) is currently considered to be
      the ultimate form of therapy for most patients with end-stage liver diseases. The
      identification of recipient and various perioperative factors that may affect the
      graft outcomes is critical. This study sought to analyze the preoperative and
      perioperative factors associated with graft outcomes in our institute. METHODS:
      This retrospective study of liver transplanted patients from January 2002 to
      December 2009 determined the incidence of 2 forms of primary dysfunction (PDF):
      Primary nonfunction (PNF) and initial poor function (IPF). RESULTS: The 97
      posttransplant patients included in the study had an average age of 52.74 years.
      The majority of indications for OLT were hepatitis B and/or C cirrhosis,
      alcoholic cirrhosis, and hepatocellular carcinoma. The incidence of PDF was 31.9%
      (31/97) with 7.2% (7/97) PNF and 24.7% (24/97) IPF. Additionally, we observed
      68.1% (66/97) to display immediate function (IF). Warm ischemic time (WIT) and
      operative time were significantly longer in the PDF compared with the IF group.
      The logistic regression model showed a WIT of >45 minutes to be a risk factor
      leading to PDF (odds ratio, 11.74; P<.05). An operative time of >6 hours and
      operative blood loss of >2 L were possible risk factors. CONCLUSION: Prolonged
      WIT (>45 minutes) was the only significant risk factor among other established
      parameters for graft function. Nevertheless, reduced operative times and blood
      loss may improve the outcomes of OLT.

PMID- 22410055
TI  - Effectiveness of intraportal prostaglandin E1 administration after liver
      transplantation.
AB  - PURPOSE: Prostaglandin E1 (PGE1) has been used to improve hepatic blood flow and
      to reduce ischemia reperfusion injuries of allografts in liver transplantation.
      However, PGE1 undergoes extensive metabolic clearance in the pulmonary and
      splanchnic circulation during intravenous administration. We analyzed the effect
      of intraportally administered PGE1. METHODS: Sixty living-donor liver transplant
      recipients received continuous infusions of PGE1 for 10 days immediately after
      the reperfusion of the allografts. Of them, 40 recipients received PGE1
      intravenously (IV group) via the internal jugular vein, and 20 recipients
      received PGE1 intraportally (IP group) through a catheter in the inferior
      mesenteric vein. Data were collected for 3 weeks postoperatively. RESULTS: The IP
      group exhibited lower initial aspartate aminotransferase and alanine
      aminotransferase levels compared with the IV group. However, no apparent
      differences were recognized in the serum albumin, total bilirubin, alkaline
      phosphatase, r-glutamyl transpeptidase, or prothrombin time levels between the 2
      groups. Chylorous ascites were observed more frequently in the IP group. There
      was no difference in portal venous flow measured by Doppler sonogram between the
      2 groups during the first postoperative week. CONCLUSION: This study demonstrated
      that intraportal administration of PGE1 had a better cytoprotective effect
      against hepatocellular damage than intravenous administration, although it did
      not have additional benefits for perihepatic hemodynamics.

PMID- 22410057
TI  - Simultaneous liver and kidney transplantation from different living donors.
AB  - OBJECTIVES: To present our experience with simultaneous living donor liver and
      kidney (SLK) transplantation from two different living donors. PATIENTS AND
      METHODS: We performed five SLK transplantations from two different living donors
      from November 2006 to December 2010. Four patients were males and one, female.
      Their age range was 47 to 66 years (mean, 55 years). The primary liver diseases
      included hepatitis B virus (n=2), alcoholic liver cirrhosis (n=2), cryptogenic
      liver disease (n=1), and hepatitis C virus with hepatocellular carcinoma (n=1).
      All five patients had chronic renal failure: four were on hemodialysis (H/D) and
      one on chronic ambulatory peritoneal dialysis for 1 to 20 years. Liver
      implantation was performed first, followed by kidney transplantation. The liver
      and kidney teams worked closely to shorten the ischemia time. RESULTS: All
      surgical procedures were performed uneventfully and all recipients and donors
      survived the operations. Good liver graft function was noted in all five
      patients. The patient with both anti-T- and anti-B-cell positive crossmatch tests
      developed hyperacute rejection of the kidney graft requiring its immediate
      removal. This patient was maintained on regular H/D afterward. The other four
      patients displayed good renal function. No evidence of severe acute rejection was
      noted during the follow-up period (range, 9-55 months) among patients treated
      with tacrolimus-based immunosuppression. CONCLUSION: We suggest that SLK
      transplantation be performed with organs from two different instead of a single
      live donor.

PMID- 22410058
TI  - Impact of hepatic macrovesicular and microvesicular steatosis on the
      postoperative liver functions after right hepatectomy in living donors.
AB  - PURPOSE: The aim of this study was to evaluate the impact of macrovesicular (MaS)
      and microvesicular steatosis (MiS) on postoperative liver function in living
      donors undergoing right hepatectomy. METHODS: We retrospectively reviewed the
      medical records of 450 living liver donors who underwent right hepatectomy
      between 2000 and 2009. First, we divided the donors into two groups according to
      the degree of MaS regardless of MiS: group MaS_5 (n=250), donors with <5% MaS and
      group MaS_30 (n=200), donors with 5% to 30% MaS. Second, we stratified donors
      according to the degree of MiS regardless of Mas: group MiS_5 (n=163), donors
      with <5% MiS, group MiS_30 (n=287), and 5%-30% MiS. We evaluated the peak values
      of total bilirubin (TB), aspartate aminotransferase (AST), and alanine
      aminotransferase (ALT) until the thirtieth postoperative day (POD). Next, we
      assessed the relation between MaS or MiS and postoperative peak liver function
      tests using regression analysis. RESULTS: Peak values of postoperative AST (227+/
      77 vs 203+/-67, respectively) and ALT (232+/-85 vs. 198+/-72, respectively) were
      significantly higher in the group MaS_30 than MaS_5. Similarly, the peak values
      of AST (225+/-80 vs 194+/-50, respectively) and ALT (228+/-85 vs 186+/-60,
      respectively) were significantly higher in the group MiS_30 than the group MiS_5.
      Regression models showed a significant modifying influence of MiS (P<0.001) on
      postoperative peak ALT levels in addition to MaS (P<.036), suggesting have
      comparable influences of both MiS and MaS on hepatic injury. CONCLUSION: Our
      results suggested that a mild degree of either MaS or MiS was associated with
      higher postoperative peak AST and ALT values. A regression analysis showed both
      MaS and MiS to display similar impacts on postoperative liver functions after
      living donor right hepatectomy.

PMID- 22410059
TI  - Younger age and presence of macrovascular invasion were independent significant
      factors associated with poor disease-free survival in hepatocellular carcinoma
      patients undergoing living donor liver transplantation.
AB  - OBJECTIVE: Patients with hepatocellular carcinoma (HCC) exceeding the University
      of California, San Francisco (UCSF) criteria are normally rejected for cadaveric
      liver transplants. However, whether they should be allowed to undergo living
      donor liver transplantation (LDLT) has been controversial. We reviewed the
      outcome of patients with advanced HCC who underwent LDLT at our center. METHODS:
      From April 2002 to May 2011, 176 patients underwent LDLT at our center; of these,
      77 (44%) had HCC at the explant liver. Patient overall survival and recurrence
      free survival (RFS) was analyzed using Kaplan-Meier method. Multivariate analysis
      was performed by Cox analysis. RESULTS: Age was 56+/-1 (56, 29-71) years; 62
      (80.5%) were male; Model for End-stage Liver Disease Score was 11+/-1 (9, 6-36),
      alpha fetoprotein (AFP) was 3683+/-2019 (69, 3-139,591) ng/L; maximum tumor size
      was 4.5 (0.5-15) cm. Number or tumor nodules was 5 (1-10), and 32 (42%) had
      macrovascular invasion diagnosed pretransplant. Eleven (14%) were within UCSF
      criteria. After follow-up of 953+/-90 (744, 2-2989) days, 53 (69%) were alive and
      48 (62%) were recurrence-free. One-, 3- and 5-year overall survival (OS) and
      recurrence-free survival (RFS) were 80%, 70%, and 57% and 80%, 65%, and 48%,
      respectively. Five-year OS and RFS for those within UCSF criteria were both 78%
      versus 55% and 46% outside UCSF criteria (P=not significant). At multivariate
      analysis, high AFP, younger age, and macrovascular invasion were associated with
      both poor RFS. CONCLUSION: In HCC patients exceeding UCSF criteria, a reasonable
      5-year overall survival of 55% post-LDLT can be obtained. Patients with HCC
      exceeding the UCSF criteria, especially in the older age group with no portal
      vein invasion and lower AFP level, should be actively considered for LDLT.

PMID- 22410060
TI  - Living donor liver transplantation for hepatocellular carcinoma: current status
      in Korea.

PMID- 22410061
TI  - Pediatric liver transplantation for hepatoblastoma: a single center experience.
AB  - The objective of this study was to review our experience with liver
      transplantation (OLT) for hepatoblastoma (HB) patients. We evaluated
      retrospectively clinical features of seven pediatric patients with HB who
      underwent OLT at our institute from 2007 to February 2011. We investigated
      pretreatment extent of disease (PRETEXT) stage at diagnosis, type of procedure,
      complications, changes in serum alpha-fetoprotein (AFP) level, recurrences and
      metastases. The median age at surgery was 47 months (range, 11 months to 10.3
      years). OLT was performed for PRETEXT stage III with a central location (n=2) and
      for PRETEXT stage IV cases (n=5). Five children underwent live donor OLT (LDLT)
      and two deceased donor OLT including one split deceased donor OLT. One patient
      received a hepatic vein stent insertion due to stenosis and another experienced
      biliary leakage which was treated with percutaneous drainage and conservative
      management. Postoperative serum AFP level remained below 20 ng/mL during follow
      up period in six patients who were free of recurrences or metastases.
      Postoperative serum AFP levels in one patient with pulmonary metastasis were
      never below 20 ng/mL and increased gradually thereafter. A Pulmonary metastasis
      was discovered in the 2nd month post-operative. The other 6 patients are free of
      tumor recurrences with 29.9 month median follow-up. Although the number of cases
      is small without long term follow-up data, OLT for unresectable HB confined to
      the liver following chemotherapy seemed to show good clinical results. The role
      of post transplantation serum AFP levels needs further investigation.

PMID- 22410062
TI  - The risk factors to predict acute rejection in liver transplantation.
AB  - PURPOSE: The aim of this study was to evaluate risk factors for an acute cellular
      rejection episode (ARE) among adult liver transplant (OLT) patients. MATERIALS
      AND METHODS: We retrospectively reviewed 110 consecutive patients who underwent
      OLT between May 2007 and December 2010. The diagnosis of ARE was based upon
      clinical and biochemical data; liver biopsy was only performed when clinical
      presentation was equivocal. We recorded donor and recipient characteristics,
      perioperative immune status, and postoperative laboratory data. Forty patients
      (36.4%) who suffered a clinical rejection episode and received pulsed or recycled
      steroid therapy (R group), were compared with 70 (63.6%) free of rejection (N
      group). RESULTS: The mean age of R recipients was 46.61+/-9.97 years, which was
      younger than the N group (51.86+/-8.37, P=.005). R group patients displayed a
      lower pre-OLT creatinine (P=.016) and higher alanine aminotransferase (P=.048).
      Cox regression model showed recipient age to be the only significant factor to
      predict ARE (odds ratio=1.071, P=.003). The cutpoint of age was 46 years by
      receiver operating characteristic analysis. Patients younger than 46 years showed
      higher initial CD8+ T-cell counts (P=.038). CONCLUSION: Recipient age was
      significantly associated with ARE; younger patients showed higher CD8+ lymphocyte
      counts than older patients. More aggressive immunosuppression should be
      considered for younger recipients to prevent ARE.

PMID- 22410063
TI  - Bortezomib is effective to treat acute humoral rejection after liver
      transplantation.
AB  - INTRODUCTION: Acute humoral rejection (AHR), a rare complication in orthotopic
      liver transplantation (OLT), responds poorly to conventional therapies.
      Bortezomib, a proteasome inhibitor, has been shown to be effective in treating
      plasma cell-derived tumors and acute rejection episodes after renal
      transplantation. Herein, we have reported our clinical experience with bortezomib
      as a novel approach to treat AHR after OLT. METHODS: We retrospectively analyzed
      the 247 adult OLTs performed from January 2007 to April 2011. Patients with AHR
      who were treated with steroid pulses, rituximab (375 mg/m2), and plasmapheresis
      (PP) were assigned to group A. Group B subjects were prescribed steroid pulses,
      rituximab, PP, and bortezomib (1.3 mg/m2), after March 2009. RESULTS: Among the 9
      patients (3.6%) diagnosed with AHR, all subjects in group A (n=3) died within
      several days after AHR, whereas 4/6 (66.7%) group B patients were rescued and 3
      (50%) survived at a mean follow-up 22.3 months (range, 18-26). CONCLUSION:
      Proteasome inhibitor-based therapies provide a more effective strategy to treat
      AHR after OLT.

PMID- 22410064
TI  - Quality of life among liver transplantation patients.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) is the treatment of choice for
      end-stage disease. It offers a chance to return to an active and prolonged life.
      Recently, more attention is being paid to the health-related quality of life
      (HRQoL) of patients and their spouses or caregivers after OLT. The aim of this
      study was to analyze the pre- versus posttransplantation HRQoL of patients and
      their spouses or caregivers using generic and disease-specific health
      questionnaires. MATERIAL AND METHODS: The study was performed between October
      2010 and January 2011 using the Short Form-36 (SF-36) and the Chronic Liver
      Disease Questionnaire (CLDQ) to evaluate the HRQoL. RESULTS: Posttransplantation
      patients (N=59, mean age 53.39 [range, 23 to 76] years, male 63.2%, female 36.8%)
      and their spouses and caregivers showed significantly better generic SF-36 HRQoL
      scores, namely, physical and social functioning, role limitations because of
      physical or emotional problems, bodily pain, vitality, as well as general and
      mental health compared with pretransplantation patients (N=57, mean age 54.56
      (range, 22 to 69) years, male 71.2%, female 28.8%). Similarly, the
      posttransplantation group showed significantly improved CLDQ scores in all
      domains: fatigue, activity, abdominal symptoms, systemic symptoms, emotional
      function, and worry. CONCLUSION: OLT improved HRQoL of end-stage liver patients
      and their spouses or caregivers.

PMID- 22410065
TI  - Dilemmas across different overseas liver transplant stages: Taiwan transplant
      recipient families' perspectives.
AB  - AIMS: This study aimed to explore the dilemmas of Taiwanese overseas liver
      transplant recipient families (OLTRF) across three overseas liver transplant
      (OLT) stages in Taiwan and Mainland China. PATIENTS AND METHODS: An exploratory
      qualitative method was employed using a purposive sample of OLTRF, who received
      guided face-to-face, semistructured interviews. Data were subjected to content
      analysis. RESULTS: Nineteen OLTRF (15 female, 4 male) aged between 29 and 71
      years (mean 55.1) for 19 patients with end-stage liver diseases were interviewed.
      OLT stages including predeparture stage (first stage), stay in China stage
      (second stage), and reentry to Taiwan stage (third stage). Ten kinds of dilemmas
      were encountered: (1) unable to get transplantation immediately (first to second
      stages); (2) dilemma of choosing overseas transplantation (first to second
      stages); (3) uncertainty about the transplantation outcomes (second to third
      stages); (4) care pressure (second to third stages); (5) poor diet adaptation
      (second to third stages); (6) lack of trust in the medical care quality (second
      stage); (7) worry about not fulfilling family responsibilities (second stage);
      (8) lack of information (all stages); (9) financial pressure (all stages); and
      (10) frustration when seeking medical care (all stages). CONCLUSIONS: Taiwanese
      OLTRF's perspectives of their dilemmas through the OLT process were first
      revealed in this study. Both Western and Eastern health professionals might be
      empowered by better understanding of OLTRF's living experiences and concerns
      during the stages of overseas liver transplantation.

PMID- 22410066
TI  - Change in the type of work of postoperative liver transplant patients.
AB  - BACKGROUND: Returning to work has been recognized as an indicator of functional
      recovery. Few studies have aimed to explore whether one's type of work changes
      after transplantation. PURPOSE: This study aims to describe the change in types
      of work in liver transplant patients. METHODS: A retrospective and descriptive
      study was conducted at a medical center in northern Taiwan. The data were
      collected by a self-report questionnaire between July and September 2010.
      Descriptive statistics an correlational analysis were used to analyze the data.
      RESULTS: A convenience sample of 111 adult liver transplant patients was included
      in this study. Of the sample, 20 patients remained unemployed, 44 had a change in
      status by becoming unemployed (n=42) or employed (n=2), and 47 patients remained
      employed after transplantation. At the time of data collection, 49 (44.1%) liver
      transplant patients were gainfully employed, a rate that was lower than that of
      the pretransplantation stage (n=89, 80.2%). The number of workers engaged in
      manual labor decreased from 40 to 18 between pre- and posttransplantation. Of the
      47 still-employed patients, 6 (12.8%) changed their occupation after
      transplantation. CONCLUSION: The rate of gainful employment after liver
      transplantation was low, and those patients who had done manual labor
      pretransplantation were no longer able to do this type of work and were
      unemployed. The still-employed patients who worked in management or were
      professionals did not change their type of work after transplantation; however,
      service and labor workers did change their type of work.

PMID- 22410067
TI  - Intracellular interferon-gamma staining analysis of donor-specific T-cell
      responses in liver transplant recipients.
AB  - OBJECTIVE: Biomarkers that accurately reflect, detect, and/or predict detrimental
      immune responses to grafts are important in organ transplantation. We established
      a new detection method for alloreactive T cells on the basis of intracellular
      staining for interferon (IFN)-gamma, using CD40-activated B cells as stimulators,
      and assessed temporal changes in alloreactive T-cell frequencies in patients who
      received liver transplantation. METHODS: Peripheral blood mononuclear cells and
      CD40-activated B cells were used as responder and stimulator cells, respectively.
      The responder cells were cultured with the stimulator cells for 7 days,
      restimulated for 5 hours, and flow cytometrically tested by intracellular
      staining for IFN-gamma. RESULTS: The relative postoperative-preoperative ratio of
      donor-specific CD8+ T cells in the nonrejection group was significantly lower
      than that in the rejection group and found to be <1 in most individuals of the
      group throughout the postoperative periods, indicating an induction of donor
      specific suppression of the CD8+ T-cell responses. In contrast, such differences
      were not found in the donor-specific CD4+ T cells. These results suggest that the
      relative postoperative-preoperative ratio of the donor-specific CD8+ T cells is a
      good indicator of graft rejection. CONCLUSION: We established a new flow
      cytometric method for the detection of alloreactive T cells by intracellular
      staining for IFN-gamma, using CD40-activated B cells as stimulator cells. Using
      this system, we found that the relative postoperative-preoperative ratio of the
      donor-specific CD8+ T cells is a possible evaluative indicator of the risk for
      graft rejection.

PMID- 22410068
TI  - Optimization of immunosuppressive therapy based on a multiparametric mixed
      lymphocyte reaction assay reduces infectious complications and mortality in
      living donor liver transplant recipients.
AB  - AIM: We investigated the clinical relevance of immune monitoring by a
      multiparametric mixed lymphocyte reaction (MLR) assay, wherein the number and
      phenotype of alloreactive precursors can be quantified by combining the results
      of carboxyfluorescein diacetate succinimidyl ester labeling and flow cytometry
      analysis. METHODS: In 51 adult patients undergoing living donor liver
      transplantation (OLT), immunosuppressive drugs were dosed on the basis of immune
      monitoring by the MLR assay (optimized protocol: group O). In 64 other patients,
      the agents were prescribed according to empirical regimens (empirical protocol:
      group E). In group O, MLR assays were performed at 2- to 4-week intervals until 3
      months after OLT and thereafter at 3- to 6-month intervals. Therapeutic
      adjustments for immunosuppressants were determined by tapering the doses in cases
      of anti-donor hyporesponsiveness for both CD4+ and CD8+ T-cell subsets. RESULTS:
      The 1-year patient and graft survivals in groups O versus E were 90.2% versus
      76.6%, respectively. The incidence of acute rejection episodes (ARE) among group
      O (13.7%) were lower than in cohort E (28.1%). None of the patients in group O
      while four patients (3%) in group E already have shown chronic rejection to date.
      The incidences of bacteremia and fungal infections in group O (9.8% and 7.5%,
      respectively) were lower than in cohort E (18.8% and 12.6%, respectively).
      CONCLUSION: A multiparametric MLR assay may facilitate the development of
      adequate immunosuppressive regimens.

PMID- 22410069
TI  - Regulatory T-cell activation among patients who displayed operational tolerance
      following intra-portal administration of donor-specific antigens in living donor
      liver transplantation.
AB  - Immunologic tolerance is the goal for all transplant surgeons. We have reported
      that repeated donor-specific antigen transfusion (DST) via the portal vein
      allowed rapid reduction of immunosuppressants with decreased acute cellular
      rejection episodes among living donor liver transplantations (LDLT). Moreover, we
      demonstrated that intraportal DST induced macrochimerism of donor type CD56+ T
      cells in the liver graft. We examined the impact of FoxP3+CD4+CD25+ T cells in
      recipients who acquired almost tolerance after LDLT with intraportal DST. We
      defined the amount of immunosuppressants administered less than one time per week
      as "almost tolerance" after LDLT, which occurred among 14% of DST patients after
      adult-to-adult LDLT. Two patients (4%) have gotten been we used from
      immunosuppressants more than 2 years after LDLT 4 years prior. We examined the
      impact of FoxP3+CD4+CD25+ T cells both in recipients with almost daily
      immunosuppressants and those who acquired almost tolerance. The proportion of
      FoxP3+/CD4+CD25+ T cells in the almost tolerance group was significantly higher
      than that in the almost daily immunosuppressant group (P<.05). The increased
      proportion of FoxP3+/CD4+CD25+ T cells significantly correlated with time after
      LRLT (y=0.0964x+42.02, R2=0.8854). Repeated intraportal DST may be a goot tool to
      induce immunologic tolerance after LDLT. Both donor type CD56+ T cells and
      FoxP3+/CD4+CD25+ T cells may act as important regulatory cells for tolerance. The
      period after LDLT is important for acquiring immunologic tolerance.

PMID- 22410070
TI  - Long-term recurrence-free survival after liver transplantation from an ABO
      incompatible living donor for treatment of hepatocellular carcinoma exceeding
      Milano criteria in a patient with hepatitis B virus cirrhosis: a case report.
AB  - The early results of liver transplantations (OLT) in patients with advanced
      hepatocellular carcinoma (HCC) were poor because of frequent tumor recurrence.
      However, OLT has significant, theoretical advantage that it removes both the
      tumor and the organ that is at a risk of malignancy. The Japanese law on organ
      transplantation limited the availability of cadaveric liver donors until its
      revision on July 17, 2011. ABO-incompatible OLT was formerly contraindicated
      because performed anti-A/B antibodies on recipient endothelial cells raised the
      risk of antibody-mediated humoral graft rejection. We have herein described four
      successful cases of steroid withdrawal among adult patients who underwent living
      donor OLT from ABO-incompatible donors. In addition, we transplanted a liver from
      a living donor into an ABO-incompatible recipient on August 9, 2004. The 55-year
      old man with HCC due to hepatitis B virus (HBV) a cirrhosis had a Child-Pugh
      score of C, and Model for End-stage Liver Disease score of 22. Two tumors greater
      than 5 cm, exceeded the Milan criteria. His des-gamma-carboxy prothrombin level
      was 6 mAu/mL, and alpha-fetoprotein, 18.78 ng/mL. Antirejection therapy included
      multiple perioperative plasmaphereses and splenectomy; with an immunosuppressive
      regimen consisting of tacrolimus, methylprednisolone, and mycophenolate mofetil.
      The maintenance dose of immunosuppression did not differ from that of ABO
      identical cases. After transplantation, we used intrahepatic arterial infusion
      therapy with prostaglandin E1 (PG E1). The patient had complications of portal
      vein thrombosis, hepatic artery thrombosis, and acute myocardial infarction,
      which were treated by interventional radiology in the posttransplantation period.
      We controlled the HBsAb titer by administering hepatitis B immunoglobulin and
      lamivudine (200 IU/L doses) for 1 year after OLT and 100 IU/L doses thereafter.
      As a result, the patient achieved long-term, disease-free graft survival without
      steroids. He currently has good liver function and leads a normal lifestyle. Our
      results suggested the feasibility of controlling antibody-mediated humoral
      rejection and other complications in living donor liver transplantations into ABO
      incompatible adults via intrahepatic arterial PG E1 infusion splenectomy, and
      plasmapheresis with regular immunosuppression. Withdrawal of steroids, HBV
      vaccination, and lamivudine, an nucleoside analog reverse transcriptase
      inhibitor, have achieved long-term (7 years) survival without recurrent HBV
      infection or tumor.

PMID- 22410071
TI  - De novo ulcerative colitis and autoimmune hepatitis after living related liver
      transplantation from cytomegalovirus-positive donor to cytomegalovirus-negative
      recipient: a case report.
AB  - BACKGROUND: De novo autoimmune hepatitis (AIH) after liver transplantation (OLT)
      has been reported; however, de novo ulcerative colitis (UC) combined with AIH
      after OLT is rare. MATERIALS AND METHODS: We report a patient who suffered de
      novo UC with AIH after living related OLT (LRLT) due to fulminant hepatitis using
      a cytomegalovirus (CMV)-positive donor to a CMV-negative recipient. RESULTS: A 32
      year-old man underwent LRLT due to fuluminant hepatis 4 years prior. He was
      admitted for colitis with diarrhea, abdominal pain, and high fever in March 2010.
      The abdominal computed tomography revealed severe jejunal edema. Anti-infectious
      therapies for bacterial, fungal, and CMV cases were ineffective. Small bowel
      endoscopy demonstrated erosion, redness, ulceration, and edema from the stomach
      to the jejunum. However, the origin of the colitis was not clear. Thereafter he
      displayed melena with a high fever and abdominal pain. The colon revealed diffuse
      inflammation with pseudopolyposis. De novo UC or CMV infection was suspected. His
      symptoms improved upon administration of salazopyrin and denosine. Moreover, he
      suffered de novo AIH, which was diagnosed by liver biopsy 3 months after the de
      novo UC. Steroid therapy improved the AIH. CONCLUSIONS: It has been reported that
      CMV is involved with UC and rejection. Our case suggested that CMV might induce
      de novo UC or AIH in CMV-negative recipients.

PMID- 22410072
TI  - Complex vascular reconstruction using donor's vessel grafts in orthotopic liver
      transplantation.
AB  - The vascular abnormalities of recipients are associated with reconstructive
      difficulties with an increased risk of postoperative complications. We performed
      an orthotopic liver transplantation that required a complex vascular
      reconstruction using donor vascular grafts. A patient with hepatitis B virus
      cirrhosis received a liver from a brain-dead donor. Dynamic computed tomography
      revealed complete obstruction of the portal vein due to thrombosis as well as
      narrowing of the hepatic arteries. We employed orthotopic liver transplantation
      using the piggy-back technique with complex reconstruction of the portal vein and
      the hepatic arteries. For portal vein reconstruction, we used the donor's iliac
      vein as an interpositional conduit from the recipient's gastric coronary vein to
      graft the portal vein. The hepatic arteries of the graft were reconstructed at
      the back-table before anastomosis to the side of superior mesenteric artery using
      an interpositional conduit of the donor's external iliac artery. All
      postoperative studies revealed good graft function with an excellent blood flow
      through all vascular anastomoses during the first year postoperatively.

PMID- 22410073
TI  - Liver transplantation surgical techniques for extensive retroperitoneal tumor
      with major blood vessel involvement: a case report.
AB  - A case of a 71-year-old man with a huge retroperitoneal tumor situated behind the
      liver, which strongly compressed the liver inferior vena cava (IVC), and
      gastrointestinal tract is described. With the techniques of whole liver
      extraction and autologous orthotopic liver transplantation, we successfully
      removed the tumor. We have the surgical techniques, essential elements, and
      indications for this procedure.

PMID- 22410074
TI  - Using ileocolic artery for successful graft salvage in a recipient with hepatic
      artery thrombosis after living donor liver transplantation: case report.
AB  - Hepatic artery (HA) occlusion is a sinister complication after liver
      transplantation. It frequently leads to graft loss if untreated. Urgent arterial
      reconstruction with thrombectomy may reduce the need for retransplantation.
      Living donor liver transplantation (LDLT) offers further challenges due to
      smaller-caliber vessels, shorter vascular stumps, and occasional multiple HA.
      Alternatives to the HA are needed when the native HA cannot be used or when HA
      complications develop. We describe the use of the recipient's ileocolic artery as
      an alternate HA in adult LDLT. Graft revascularization and timely salvage
      resulted in good patient recovery. A 6-month computed tomography angiography
      follow-up showed patency of the alternate vessels reconstructed.

PMID- 22410075
TI  - Right posterior portal vein stenosis developed after living donor liver
      transplantation using a modified right lobe graft with a type 2 portal vein: a
      case report.
AB  - Portal vein complications after liver transplantation (LT) can lead to graft
      liver failure. In this living donor liver transplantation case a stenosis
      developed in the right posterior branch of the portal vein of the graft liver
      from a living donor with type 2 portal vein variation. A 61-year-old woman
      diagnosed with hepatocellular carcinoma due to hepatitis B received a liver graft
      revealing a single lumen divided by a septum. The portal vein was anastomosed to
      the recipient portal vein without venoplasty. Postoperative Doppler sonogram
      revealed poor flow in the right posterior portal vein with compensatory arterial
      hyperperfusion. The postoperative computed tomography (CT) scan revealed
      narrowing of the proximal part of the right posterior portal vein with periportal
      tracking. Without intervention, the liver enzyme and bilirubin levels decreased
      to normal and the follow-up CT scan showed decreased periportal tracking. The
      patient was discharged without major complications. We believe that the posterior
      portal vein stenosis resulted from the direct anastomosis of the portal vein
      without a further venoplasty. Although there was no major complication due to the
      posterior portal vein stenosis in our patient, we suggest a venoplasty to prevent
      portal vein stenosis when using right lobe grafts with a type 2 portal vein, even
      if a single lumen is present and there is a margin for a direct anastomosis.

PMID- 22410076
TI  - Isolated dissection of the superior mesenteric artery after living donor liver
      transplantation: a case report.
AB  - Isolated dissection of the superior mesenteric artery (SMA) not associated with
      aortic dissection is rare, particularly after living donor liver transplantation
      (LDLT). We experienced a case of isolated dissection of the SMA after LDLT
      performed in a 56-year-old man diagnosed with hepatitis B virus-related cirrhosis
      and hepatocellular carcinoma within the Milan criteria. He had no past history of
      hypertension or diabetes mellitus. At 6 days after LDLT, the patient underwent an
      emergency portal vein thrombectomy with ligation of a huge left gastric vein
      shunt. Thereafter anticoagulant and antiplatelet therapy were initiated. At 12
      days after LDLT, a contrast-enhanced computer assisted tomography (CT) scan
      revealed the presence of a thrombus in a false lumen and a thin flap enlarged in
      the SMA. Because he presented neither abdominal pain nor biochemical data
      suggesting mesenteric ischemia, he was treated with antihypertensive agents in
      addition to anticoagulant and antiplatelet therapy. The thrombus in the false
      lumen was reduced and the intimal flap in the SMA disappeared according to the
      results of a CT scan 4 months after LDLT. He has remained free of symptoms for 4
      years. The strategy to treat isolated SMA dissection is not well established.
      Urgent surgery is indicated for acute symptomatic forms with a suspicion of
      mesenteric ischemia; conservative treatment is indicated for patients with
      minimal, resolving, or no pain, but requires close follow-up.

PMID- 22410077
TI  - The inferior mesenteric vein to the left gonadal vein shunt for gastroesophageal
      varices and extrahepatic portal vein thrombosis after living donor liver
      transplantation: a case report.
AB  - This 59-year-old woman underwent living donor liver transplantation using a left
      lobe graft as an aid for autoimmune hepatitis in 2003. Splenectomy was also
      performed because of blood type incompatibility. Follow-up endoscopic and
      computed tomography examinations showed gastroesophageal varices with extra
      hepatic portal vein thrombosis in 2007 that increased (esophageal varices [EV]:
      locus superior [Ls], moderately enlarged, beady varices [F2], Blue varices [Cb],
      presence of small in number and localized red color sign [RC1] and telangiectasia
      [TE+], gastric varices [GV]: extension from the cardiac orifice to the fornix [Lg
      cf], moderately enlarged, beady varices [F2], white varices [Cw], absence of red
      color sign [RC-]). Portal venous flow to the gastroesophageal varices was also
      confirmed from a large right gastric vein. The splenic vein was thrombosed. Blood
      flow to the liver graft was totally supplied from the hepatic artery. The graft
      was functioning well. Because these gastroesophageal varices had a high risk of
      variceal bleeding, we decided to proceed with a portal reconstruction of a
      surgical portosystemic shunt in 2008. Severe adhesions were observed around the
      portal vein. It was impossible to perform portal reconstruction. There were
      relatively fewes adhesious in the left lower side of the abdominal cavity. We
      decided to create an inferior mesenteric vein to left gonadal vein shunt. The
      portal vein pressure decreased from 31.0 to 21.5 cm H2O thereafter. The
      postoperative course was smooth without any complication. This patient was
      discharged on the postoperative day 15. Follow-up endoscopic study showed the
      improvement in the gastroesophageal varices (EV: Ls, F2, Cb, RC(-), GV: Lg-c, F2,
      Cw, RC-) at 3 months after the operation. We also comfirmed the patency of the
      shunt by serial computed tomography examinations.

PMID- 22410079
TI  - Infant mortality in Brazil, 1980-2000: a spatial panel data analysis.
AB  - BACKGROUND: Infant mortality is an important measure of human development,
      related to the level of welfare of a society. In order to inform public policy,
      various studies have tried to identify the factors that influence, at an
      aggregated level, infant mortality. The objective of this paper is to analyze the
      regional pattern of infant mortality in Brazil, evaluating the effect of
      infrastructure, socio-economic, and demographic variables to understand its
      distribution across the country. METHODS: Regressions including socio-economic
      and living conditions variables are conducted in a structure of panel data. More
      specifically, a spatial panel data model with fixed effects and a spatial error
      autocorrelation structure is used to help to solve spatial dependence problems.
      The use of a spatial modeling approach takes into account the potential presence
      of spillovers between neighboring spatial units. The spatial units considered are
      Minimum Comparable Areas, defined to provide a consistent definition across
      Census years. Data are drawn from the 1980, 1991 and 2000 Census of Brazil, and
      from data collected by the Ministry of Health (DATASUS). In order to identify the
      influence of health care infrastructure, variables related to the number of
      public and private hospitals are included. RESULTS: The results indicate that the
      panel model with spatial effects provides the best fit to the data. The analysis
      confirms that the provision of health care infrastructure and social policy
      measures (e.g. improving education attainment) are linked to reduced rates of
      infant mortality. An original finding concerns the role of spatial effects in the
      analysis of IMR. Spillover effects associated with health infrastructure and
      water and sanitation facilities imply that there are regional benefits beyond the
      unit of analysis. CONCLUSIONS: A spatial modeling approach is important to
      produce reliable estimates in the analysis of panel IMR data. Substantively, this
      paper contributes to our understanding of the physical and social factors that
      influence IMR in the case of a developing country.

PMID- 22410078
TI  - Brain activation during fear conditioning in humans depends on genetic variations
      related to functioning of the hypothalamic-pituitary-adrenal axis: first evidence
      from two independent subsamples.
AB  - BACKGROUND: Enhanced acquisition and delayed extinction of fear conditioning are
      viewed as major determinants of anxiety disorders, which are often characterized
      by a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis. METHOD: In this
      study we employed cued fear conditioning in two independent samples of healthy
      subjects (sample 1: n=60, sample 2: n=52). Two graphical shapes served as
      conditioned stimuli and painful electrical stimulation as the unconditioned
      stimulus. In addition, guided by findings from published animal studies on HPA
      axis-related genes in fear conditioning, we examined variants of the
      glucocorticoid receptor and corticotropin-releasing hormone receptor 1 genes.
      RESULTS: Variation in these genes showed enhanced amygdala activation during the
      acquisition and reduced prefrontal activation during the extinction of fear as
      well as altered amygdala-prefrontal connectivity. CONCLUSIONS: This is the first
      demonstration of the involvement of genes related to the HPA axis in human fear
      conditioning.

PMID- 22410080
TI  - Production of flavor esters catalyzed by CALB-displaying Pichia pastoris whole
      cells in a batch reactor.
AB  - Candida antarctica lipase B (CALB) has been employed as an efficient catalyst in
      the preparation of many flavor esters. A CALB-displaying yeast whole-cell
      biocatalyst could be an attractive alternative to commercial immobilized CALB
      because of its low-cost preparation and high enzymatic activity. We investigated
      the potential application of CALB-displaying Pichia pastoris cells for the
      production of flavor esters. The optimal conditions for flavor esters synthesis
      by this biocatalyst were determined in 50-ml shake flasks. Under optimized
      conditions, the synthesis of 12 kinds flavor esters were scaled up in a 5-l batch
      stirred reactor. Among these, the mole conversions of 10 exceeded 95% after
      reactions for 4h. In addition, this biocatalyst showed good tolerance for high
      substrates concentration and excellent operational stability. Repeated use of the
      cells in 10 batches resulted in an activity loss of less than 10%. Thus, CALB
      displaying P. pastoris whole cells are robust biocatalysts with potential
      commercial application in the large-scale production of flavor esters in non
      aqueous media.

PMID- 22410082
TI  - Time-course recovery of estrogen-responsive genes of a cichlid fish exposed to
      waterborne octylphenol.
AB  - The aim of this study was to describe the time-course of estrogen-induced gene
      expression, corresponding plasma protein detection and histological alterations
      after cessation of octylphenol (OP) exposure of Cichlasoma dimerus, to test
      differential responses of biomarkers suitable for environmental monitoring. Male
      fish were exposed to a nominal concentration of 150 MUg/L OP for 28 days, and
      later transferred to OP-free water aquaria for 1, 3, 7, 14, 21 or 28 days. Blood
      and mucus samples were obtained in order to analyze vitellogenin (VTG) and zona
      pellucida (ZP) proteins by Western blot; liver samples were used for gene
      expression and to assess tissue damage and further recovery of all the analyzed
      endpoints. Partial sequences of C. dimerus VTG and Na+/K+-ATPase were obtained.
      Comparison with VTGs of several teleosts supports that the partial sequence
      obtained for C. dimerus belongs to VTGAb type. ZP and VTG expression was highly
      up-regulated by OP. Immunoreactive (ir-) bands of 62, 52 and 50 kDa for ZP and
      140, 103, 75 and 64 kDa for VTG, were detected after 28 days of OP exposure in
      plasma and mucus samples. After transfer of treated fish to clean water, ZP ir
      bands in plasma disappeared rapidly (day 3), while VTG ir-bands decreased
      gradually; no ir-bands were detected on day 28 of recovery. Similarly, ZPB
      transcripts abruptly returned to background levels (day 3), earlier than for ZPC
      (day 7) or VTG (day 14). Liver from OP treated fish showed tissue disarrangement,
      eccentric and euchromatic hepatocytes nuclei and intense perinuclear basophilia.
      After the recovery period, these changes were still evident though less
      pronounced, accounting for irreversibility of tissue damage or the requirement
      for a longer period of depuration. The present results confirm that for
      biochemical and molecular biomarkers, such as induction of female proteins in
      male fish exposed to OP, complete recovery is achieved after adequate time of
      depuration (28 days). Male ZPB expression reflects a recent exposure to
      estrogenic contaminants, while VTG may reveal past exposures. The combination of
      biomarkers with different temporal responses such as C. dimerus ZP and VTG
      provides a more comprehensive interpretation of pollution status.

PMID- 22410083
TI  - Consequences of linker length alteration of the alpha7 nicotinic acetylcholine
      receptor (nAChR) agonist, SEN12333.
AB  - A series of ligands based on SEN12333, containing either contracted or elongated
      alkyl chains, were synthesized and evaluated in molecular docking studies against
      a homology model of the alpha7 nicotinic acetylcholine receptor (nAChR) subtype.
      The predicted binding of all ligands was highly similar, with the exception of
      the analog containing a 5 methylene unit spacer. However, in vitro competition
      binding assays revealed that the ligands possessed dissimilar binding affinities,
      with a K(i) range of more than an order of magnitude (K(i)=0.50 to >10 MUM), and
      only SEN12333 itself exhibited functional activity at the alpha7 nAChR.

PMID- 22410081
TI  - The Valley of Death in anticancer drug development: a reassessment.
AB  - The past decade has seen an explosion in our understanding of cancer biology and
      with it many new potential disease targets. Nonetheless, our ability to translate
      these advances into therapies is poor, with a failure rate approaching 90%. Much
      discussion has been devoted to this so-called 'Valley of Death' in anticancer
      drug development, but the problem persists. Could we have overlooked some
      straightforward explanations to this highly complex problem? Important aspects of
      tumor physiology, drug pharmacokinetics, preclinical models, drug delivery, and
      clinical translation are not often emphasized, but could be crucial. This
      perspective summarizes current views on the problem and suggests feasible
      alternatives.

PMID- 22410084
TI  - Design and synthesis of a vialinin A analog with a potent inhibitory activity of
      TNF-alpha production and its transformation into a couple of bioprobes.
AB  - Vialinin A (1) is an extremely potent inhibitor against tumor necrosis factor
      (TNF)-alpha production in rat basophilic leukemia (RBL-2H3) cells. This Letter
      describes the design and synthesis of its advanced analog, 5',6'-dimethyl
      1,1':4'1"-terphenyl-2',3',4,4"-tetraol (2) with a comparable inhibitory activity
      (IC(50)=0.02 nM) to that of 1. The synthesis involved double Suzuki-Miyaura
      coupling as a key step, and required only five steps from commercially available
      3,4-dimethylphenol. For identification of the target molecule, fluorescent and
      biotinylated derivatives of 2 were prepared through a 'click' coupling process.

PMID- 22410085
TI  - Measuring free bilirubin: the clinical perspective.

PMID- 22410086
TI  - How safe is the outpatient management of patients with acute chest pain and
      mildly increased cardiac troponin concentrations?
AB  - BACKGROUND: The appropriate management of patients discharged from the emergency
      department (ED) with increased high-sensitivity cardiac troponin T (hs-cTnT) but
      normal or borderline-high conventional cardiac troponin concentrations is
      unknown. METHODS: We investigated 643 consecutive ED patients with acute chest
      pain who had been discharged for outpatient management after acute myocardial
      infarction (AMI) had been ruled out by serial measurements of conventional
      cardiac troponin. hs-cTnT was measured blindly, and we calculated the rates of
      all-cause mortality (primary endpoint) and subsequent AMI (secondary endpoint) at
      30, 90, and 360 days. RESULTS: hs-cTnT concentrations were increased (>14 ng/L)
      in 114 patients (18%) but <30 ng/L in 95% of these patients. Of those 114
      patients, 96 (84%) had an adjudicated noncoronary cause of chest pain. Thirty-day
      mortality (95% CI) was 0.9% (0.1%-6.1%), 90-day mortality was 2.7% (0.9%-8.1%),
      and 360-day mortality was 5.2% (2.2%-11.9%) in patients with increased hs-cTnT;
      respective rates (95% CI) of AMI were 0.0%, 1.9% (0.5%-7.2%), and 7.6% (3.7%
      15.3%). Increased hs-cTnT was associated with increased mortality and AMI at 90
      days (P = 0.006 and P = 0.081, respectively) and 360 days (P = 0.001 for both).
      CONCLUSIONS: hs-cTnT is a strong prognosticator of intermediate and long-term
      mortality and AMI in low-risk patients discharged from the ED after AMI has been
      ruled out. The relatively low rate of 30-day events may suggest that patients
      without acute coronary syndrome and small increases in cardiac troponin are in
      need of further investigations and treatments, but not necessarily immediate
      hospitalization.

PMID- 22410087
TI  - Liquid chromatography-tandem mass spectrometry work flow for parallel
      quantification of methotrexate and other immunosuppressants.

PMID- 22410088
TI  - Systematic evaluation of supported liquid extraction in reducing matrix effect
      and improving extraction efficiency in LC-MS/MS based bioanalysis for 10 model
      pharmaceutical compounds.
AB  - In past a few years, there has been a large increase in the application of
      supported liquid extraction (SLE) for LC-MS/MS based bioanalysis due to its
      distinct practical advantage in reduced time cost, ease of operation and the
      feasibility for automation. The main purpose of this study was to systematically
      evaluate supported liquid extraction in reducing matrix effect and improving
      extraction efficiency/recovery under various extraction conditions with 10 model
      pharmaceutical compounds in liquid chromatography coupled to electrospray tandem
      mass spectrometry (LC-ESI-MS/MS) analysis. Selected compounds have diverse
      physicochemical properties where logP ranges from 0.1 to 6.24 and pK(a) ranges
      from 4.0 to 11.1. The factors that may have the impact on the recovery of
      analytes and phospholipids (PL) were assessed. Over 75% recovery was achieved for
      every analyte under its respectively optimized extraction conditions where the
      selection of the polarity of extraction solvent and buffered pH can be critical
      for efficient recovery. Furthermore, the matrix effect was assessed by
      postextraction spike and postcolumn infusion method. The matrix effect was
      considerably reduced for all analytes under most extraction conditions evaluated
      for SLE, compared with protein precipitation (PPT) method. The correlation
      between matrix effect and residual phospholipids in sample extract was clearly
      shown. Although analyte-dependent matrix effect was observed prominently in
      sample extract prepared by PPT, it was minimized by SLE sample preparation
      process that effectively removes the majority of phospholipids. Sample extracted
      by ethyl acetate contained more phospholipids and demonstrated stronger matrix
      effect than by other organic solvents. Water-miscible organic content, such as
      methanol and acetonitrile in samples prior to loading has significant impact on
      PL recovery when eluting with methyl tert-butyl ether. However, isopropanol does
      not enhance the recovery of PL when adding to dichloromethane for elution. In
      addition, the compromise between improved extraction efficiency by SLE and
      reduced matrix effect is sometimes necessary to yield clean extract with
      acceptable recovery. The effective removal of phospholipids and reduction of
      matrix effect, while achieving good recovery for all pharmaceutical compounds
      with diverse physicochemical properties, demonstrated that SLE is a valuable
      alternative technique to liquid-liquid extraction (LLE) in high throughput LC
      MS/MS based bioanalysis.

PMID- 22410089
TI  - Simultaneous determination of 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)
      uracil (FAU) and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl) 5-methyluracil
      (FMAU) in human plasma by liquid chromatography/tandem mass spectrometry.
AB  - A liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) assay
      was developed and validated for simultaneous determination of 1-(2'-deoxy-2'
      fluoro-beta-D-arabinofuranosyl) uracil (FAU) and its active metabolite 1-(2'
      deoxy-2'-fluoro-beta-D-arabinofuranosyl) 5-methyluracil (FMAU) in human plasma.
      FAU and FMAU were extracted from plasma samples using solid-phase extraction with
      Waters Sep-Pak(r) Vac C18 cartridge. Chromatographic separation was achieved on a
      Waters Atlantis T3 C18 column with a gradient mobile phase consisting of methanol
      and water with 0.45% formic acid (v/v) running at a flow rate of 0.2 ml/min. The
      analytes were monitored by triple quadrupole mass spectrometer under positive
      ionization mode. The lower limit of quantitation (LLOQ) was 10 and 2 ng/ml for
      FAU and FMAU in plasma, respectively. Calibration curves were linear over FAU and
      FMAU plasma concentration range of 10-2000 and 2-1000 ng/ml, respectively. The
      intra-day and inter-day accuracy and precision were within the generally accepted
      criteria for bioanalytical method (<15%). The method has been successfully
      employed to characterize the plasma pharmacokinetics of FAU and FMAU in cancer
      patients receiving 1-h intravenous infusion of FAU 50 mg/m2.

PMID- 22410090
TI  - Ethnoracial differences in anxiety sensitivity: examining the validity of
      competing anxiety sensitivity index subscales.
AB  - Despite the increasing number of Americans who are considered to be a part of an
      ethnoracial minority group, there have been few investigations of the cross
      cultural validity of measures of psychopathology. The limited existing literature
      suggests potential differences between African American (AA) and European
      American (EA) individuals with respect to the utility of self-report measures,
      including anxiety sensitivity. Physical, mental, and social domains of anxiety
      sensitivity are measured using subscales derived from a 3-factor model reported
      in EA samples despite evidence suggesting that anxiety sensitivity in AA samples
      is characterized by more distinct physical concerns. The current study compared
      the concurrent and predictive validity of the traditional anxiety sensitivity
      subscales representing 3 domains and a 4-subscale formulation based on
      predictions about the construct in AA samples. Comparisons of both AA (N=41) and
      EA (N=298) samples are included. Findings suggest some ethnoracial group
      differences in the concurrent and predictive validity of anxiety sensitivity
      subscales, specifically supporting the appropriateness and specificity of the 4
      factor model of anxiety sensitivity in AA samples. Implications are discussed,
      including identification of sociocultural mechanisms that might influence
      psychometric properties of measures of anxiety.

PMID- 22410091
TI  - Family orientation, language, and anxiety among low-income Latino youth.
AB  - There is emerging evidence that Latino youth report higher levels of anxiety
      symptoms than children from other ethnic groups. Although often implicated,
      cultural variables have not been systematically evaluated to determine their
      relationship to anxiety symptoms in Latino youth. The present study examined
      family orientation values, as measured by family obligation and affiliative
      obedience, and their relationship to youth anxiety symptoms. The sample consisted
      of 133 Latino students (grades 5th through 7th) of low-income backgrounds in an
      urban public school setting. Structural equation models revealed that higher
      family orientation was associated with separation anxiety/panic (beta=.32) and
      harm avoidance (beta=.51). Models employing language proficiency and use mirrored
      those employing family orientation, suggesting that language fluency captures, in
      part, family socialization values. The results provide support for the impact of
      culture in the assessment and specific needs of Latino youth with anxiety
      problems.

PMID- 22410092
TI  - Race and ethnicity as central constructs in our assessment and treatment of
      anxiety. Foreword.

PMID- 22410093
TI  - Contextual factors and anxiety in minority and European American youth presenting
      for treatment across two urban university clinics.
AB  - The current study compared ethnic minority and European American clinically
      referred anxious youth (N=686; 2-19 years) on internalizing symptoms (i.e.,
      primary anxiety and comorbid depression) and neighborhood context. Data were
      provided from multiple informants including youth, parents, and teachers.
      Internalizing symptoms were measured by the Multidimensional Anxiety Scale for
      Children, Child Depression Inventory, Child Behavior Checklist and Teacher Report
      Form. Diagnoses were based on the Anxiety Disorders Interview Schedule for
      Children. Neighborhood context was measured using Census tract data (i.e., owner
      occupied housing, education level, poverty level, and median home value). Ethnic
      minority and European American youth showed differential patterns of diagnosis
      and severity of anxiety disorders. Further, ethnic minority youth lived in more
      disadvantaged neighborhoods. Ethnicity and neighborhood context appear to have an
      additive influence on internalizing symptoms in clinically-referred anxious
      youth. Implications for evidence-based treatments are discussed.

PMID- 22410094
TI  - Barriers to treatment among African Americans with obsessive-compulsive disorder.
AB  - African Americans are underrepresented in OCD treatment centers and less likely
      to experience a remission of symptoms. This study examines the barriers that
      prevent African Americans with OCD from receiving treatment. Seventy-one adult
      African Americans with OCD were recruited and administered the modified Barriers
      to Treatment Participation Scale (BTPS) and the Barriers to Treatment
      Questionnaire (BTQ). Comparing the BTQ between a European American Internet
      sample (N=108) and the African American OCD sample (N=71) revealed barriers
      unique to African Americans, including not knowing where to find help and
      concerns about discrimination. A Mokken Scale Analysis of the BTPS in the African
      American participants identified seven major barriers, including the cost of
      treatment, stigma, fears of therapy, believing that the clinician will be unable
      to help, feeling no need for treatment, and treatment logistics (being too busy
      or treatment being too inconvenient). Pearson and point-biserial correlations of
      the scales and demographic and psychological variables were conducted.
      Significant relationships emerged between age, gender, income, education,
      insurance status, and ethnic affirmation/belonging among several of the Mokken
      scales. A one-way ANOVA demonstrated that concerns about cost were significantly
      greater for those without insurance, versus those with public or private plans.
      Suggestions for overcoming barriers are presented, including community education,
      affordable treatment options, and increasing cultural competence among mental
      health providers.

PMID- 22410096
TI  - Correlation of Ataxia-Telangiectasia-Mutated (ATM) gene loss with outcome in head
      and neck squamous cell carcinoma.
AB  - OBJECTIVES: Ataxia-Telangiectasia-Mutated (ATM) gene loss has been associated
      with poor prognosis and treatment resistance in head and neck squamous cell
      carcinomas (HNSCC). We investigated the relationship between ATM loss detected by
      fluorescence in-situ hybridisation (FISH) with patient outcome, and its
      relationship with Human Papillomavirus (HPV)/p16(INK4A) status. MATERIAL AND
      METHODS: Copy number of the ATM gene and chromosome 11 were determined by FISH
      and HPV status was determined using p16(INK4A) immunohistochemistry in 87
      paraffin embedded tumour samples from patients with HNSCC treated with
      chemoradiation at a single institution. ATM loss was correlated with patient
      outcome as both a continuous and dichotomous variable. RESULTS: Of 73 evaluable
      patients, 44 (60.3%) demonstrated loss of the ATM gene. There was no correlation
      between ATM loss (defined as a mean ratio of ATM: chromosome 11<0.75) and overall
      survival (OS, p=0.67) or time to locoregional failure (TTLRF, p=0.72). Similarly,
      when evaluated as a continuous variable there was no significant relationship
      between ATM loss and patient outcome (OS, p=0.89; TTLRF, p=0.21). No significant
      relationship was found between p16(INK4A) status and ATM loss, for patient
      outcome. We found 35.6% (n=26) of patients demonstrated polysomy of chromosome 11
      (defined as the presence of a mean >2.5 copies of chromosome 11) which was
      significantly associated with p16(INK4A) negative status (p=0.0004), but did not
      influence outcome. CONCLUSIONS: ATM loss is a frequent event in HNSCC, however it
      does not impact outcome after treatment with chemoradiation. Polysomy of
      chromosome 11 was significantly associated with p16(INK4A) negative status but
      also lacks prognostic significance.

PMID- 22410095
TI  - The Harvard/Brown Anxiety Research Project-Phase II (HARP-II): rationale,
      methods, and features of the sample at intake.
AB  - We describe the rationale, method, and intake demographic and clinical findings
      of the Harvard/Brown Anxiety Research Project-Phase II (HARP-II). HARP-II is the
      first prospective, observational, longitudinal study to describe the
      characteristics and course of anxiety in African American, Latino, and Non-Latino
      White individuals. Participants met criteria for at least one of the following
      disorders: Generalized Anxiety Disorder, Social Phobia, Panic Disorder with or
      without Agoraphobia, Agoraphobia without history of Panic Disorder, Post
      traumatic Stress Disorder. Initial intake data, collected between 2004 and 2011,
      are presented for 165 African American, 150 Latino, and 172 Non-Latino White
      participants. Participants evidenced substantial psychiatric comorbidity (mean
      number of Axis I disorders=3.4), and moderate to severe symptoms and functional
      impairment. HARP-II will examine clinical course, in the context of potential
      socio-cultural and individual moderators (e.g., discrimination, acculturation,
      negative affect). Results should lead to improved understanding, prognostics, and
      treatment of anxiety in diverse populations.

PMID- 22410097
TI  - Using human-centered design to improve the assault rifle.
AB  - The objective of the present study was to interview infantry soldiers to
      determine their preferences with respect to rifle design and to examine the
      effect of buttstocks on shooting performance. Factor analysis showed that seven
      main factors should be considered in rifle redesign including tactics necessary,
      interface design, saving weight, bullpup configuration, sight design, other
      devices, and bayonet lug. For the shooting experiment, a total of four shooting
      trials were performed with the T-91 rifle, with buttstock lengths of 26 mm, 34
      mm, self-adjusting stock, and bullpup stock. The analysis revealed that buttstock
      length had a significant effect on shooting performance. The redesigned rifle
      weight and total length should be reduced to 3.2 kg and 750 mm, respectively. The
      rifle buttstock should be a non-adjustable bullpup style. The buttstock shape
      should be curved and the hand-guard type should be more deeply and density seams,
      while the trigger handle shape should be slanted.

PMID- 22410098
TI  - Synovial fluid metabolomics in different forms of arthritis assessed by nuclear
      magnetic resonance spectroscopy.
AB  - OBJECTIVES: Currently there are no reliable biomarkers in the synovial fluid
      available to differentiate between septic and non-septic arthritis or to predict
      the prognosis of osteoarthritis, respectively. Nuclear magnetic resonance (NMR)
      spectroscopy is an analytical technique that allows a rapid, high throughput
      metabolic profiling of biological fluids or tissues. METHODS: Proton (1H)-nuclear
      magnetic resonance (NMR) spectroscopy was performed in synovial fluid samples
      from patients with septic arthritis, crystal arthropathy, different forms of
      inflammatory arthritis or osteoarthritis (OA). The metabolic environment based on
      the low molecular weight components was compared in disease subsets and principal
      component analysis (PCA) was performed. RESULTS: Fifty-nine samples from patients
      with OA, gout, calcium pyrophosphate disease, spondylarthritis, septic arthritis
      and rheumatoid arthritis (RA) were analysed. NMR yielded stable and reproducible
      metabolites over time. Thirty-five different metabolites as well as paracetamol
      and ibuprofen were identified in synovial fluid. The metabolic profile of septic
      arthritis assessed by PCA was distinguishable from the other samples whereas no
      differences were seen in OA compared to crystal-associated arthritis, RA or
      spondylarthritis. CONCLUSIONS: 1H-NMR is a fast analytic tool with possible
      implications in synovial fluid diagnostics. A distinctive metabolism is observed
      in septic arthritis whereas metabolites in OA are similar to those in
      inflammatory arthritis.

PMID- 22410099
TI  - Quantification of atopy, lung function and airway hypersensitivity in adults.
AB  - BACKGROUND: Studies in children have shown that concentration of specific serum
      IgE (sIgE) and size of skin tests to inhalant allergens better predict wheezing
      and reduced lung function than the information on presence or absence of atopy.
      However, very few studies in adults have investigated the relationship of
      quantitative atopy with lung function and airway hyperresponsiveness (AHR).
      OBJECTIVE: To determine the association between lung function and AHR and
      quantitative atopy in a large sample of adults from the UK. METHODS: FEV1 and FVC
      (% predicted) were measured using spirometry and airway responsiveness by
      methacholine challenge (5-breath dosimeter protocol) in 983 subjects (random
      sample of 800 parents of children enrolled in a population-based birth cohort
      enriched with 183 patients with physician-diagnosed asthma). Atopic status was
      assessed by skin prick tests (SPT) and measurement of sIgE (common inhalant
      allergens). We also measured indoor allergen exposure in subjects' homes.
      RESULTS: Spirometry was completed by 792 subjects and 626 underwent methacholine
      challenge, with 100 (16.0%) having AHR (dose-response slope>25). Using sIgE as a
      continuous variable in a multiple linear regression analysis, we found that
      increasing levels of sIgE to mite, cat and dog were significantly associated with
      lower FEV1 (mite p = 0.001, cat p = 0.0001, dog p = 2.95 * 10-8). Similar
      findings were observed when using the size of wheal on skin testing as a
      continuous variable, with significantly poorer lung function with increasing skin
      test size (mite p = 8.23 * 10-8, cat p = 3.93 * 10-10, dog p = 3.03 * 10-15,
      grass p = 2.95 * 10-9). The association between quantitative atopy with lung
      function and AHR remained unchanged when we repeated the analyses amongst
      subjects defined as sensitised using standard definitions (sIgE>0.35 kUa/l, SPT-3
      mm>negative control). CONCLUSIONS: In the studied population, lung function
      decreased and AHR increased with increasing sIgE levels or SPT wheal diameter to
      inhalant allergens, suggesting that atopy may not be a dichotomous outcome
      influencing lung function and AHR.

PMID- 22410100
TI  - Inhibition of inflammation but not ankylosis by glucocorticoids in mice: further
      evidence for the entheseal stress hypothesis.
AB  - INTRODUCTION: Studies in the spontaneous ankylosis model in aging male DBA/1 mice
      and in patients with ankylosing spondylitis provide evidence that inflammation
      and new tissue formation leading to joint or spine ankylosis are likely linked
      but largely uncoupled processes. We previously proposed the 'entheseal stress'
      hypothesis that defines microdamage or cell stress in the enthesis as a trigger
      for these disease processes. Here, we further investigated the relationship
      between inflammation and ankylosis by focusing on the early phase of the
      spontaneous arthritis model. METHODS: Aging male DBA/1 mice from different
      litters were caged together at the age of ten weeks and studied for signs of
      arthritis. A group of DBA/1 mice were treated daily with dexamethasone (0.5 MUg/g
      body weight). Severity of disease was assessed by histomorphology and by positron
      emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) as a
      tracer. Bone loss in dexamethasone-treated or control mice was determined by in
      vivo dual-energy X-ray absorptiometry. Chemokine gene expression was studied ex
      vivo in dissected paws and in vitro in mesenchymal cells (periosteal and bone
      marrow stromal cells) by quantitative real-time PCR in the presence or absence of
      bone morphogenetic protein 2 (BMP2) and dexamethasone. RESULTS: Dexamethasone
      treatment did not affect incidence or severity of ankylosis, but led to an
      expected reduction in inflammation in the paws at week 15 as measured by PET
      tracer uptake. Treatment with dexamethasone negatively affected bone mineral
      density. Chemokines attracting neutrophils and lymphocytes were expressed in
      affected paws. In vitro, BMP2 stimulation upregulated chemokines in different
      mesenchymal joint-associated cell types, an effect that was inhibited by
      dexamethasone. CONCLUSIONS: BMP signaling may be a trigger for both inflammation
      and ankylosis in the spontaneous model of ankylosing enthesitis. The lack of
      inhibition by glucocorticoids on new bone formation while causing systemic bone
      loss highlights the paradoxical simultaneous loss and gain of bone in patients
      with ankylosing spondylitis.

PMID- 22410102
TI  - The moderating role of decision authority and coworker- and supervisor support on
      the impact of job demands in nursing homes: a cross-sectional study.
AB  - BACKGROUND: Healthcare workers in nursing homes are faced with high job demands
      that can have a detrimental impact on job-related outcomes, such as job
      satisfaction. Job resources may have a buffering role on this relationship. The
      Demand-Control-Support (DCS) Model offers a theoretical framework to study how
      specific job resources can buffer the adverse effects of high demands, and can
      even activate positive consequences of high demands. OBJECTIVES: The present
      study tests the moderating (i.e. buffering and activating) effects of decision
      authority and coworker- and supervisor support that are assumed by the hypotheses
      of the DCS Model. DESIGN: A national cross-sectional survey was conducted with an
      anonymous questionnaire. SETTING: One hundred and thirty six living arrangements
      that provide nursing home care for people with dementia in the Netherlands.
      PARTICIPANTS: Fifteen healthcare workers per living arrangement. In total, 1147
      people filled out the questionnaires (59% response rate). METHODS: Hierarchical
      multilevel regression analyses were conducted to test the assumption that the
      effect of job demands on the dependent variables is buffered or activated the
      most when both decision authority and social support are high. This moderation is
      statistically represented by three-way interactions (i.e.
      demands*authority*support), while lower-order effects are taken into account
      (i.e. two-way interactions). The hypotheses are supported when three-way
      interaction effects are found in the expected direction. The dependent variables
      studied are job satisfaction, emotional exhaustion, and personal accomplishment.
      RESULTS: The proposed buffering and activation hypotheses of the DCS Model were
      not supported in our study. Three-way interaction effects were found for
      emotional exhaustion and personal accomplishment, though not in the expected
      direction. In addition, two-way interaction effects were found for job
      satisfaction and emotional exhaustion. Decision authority was found to buffer the
      adverse effect of job demands and to activate healthcare staff. Supervisor
      support was found to buffer the adverse effect of job demands on emotional
      exhaustion in situations with low decision authority. Finally, coworker support
      was found to have an adverse effect on personal accomplishment in high strain
      situations. CONCLUSIONS: Findings reveal that decision authority in particular
      makes healthcare workers in nursing homes less vulnerable to adverse effects of
      high job demands, and promotes positive consequences of work.

PMID- 22410101
TI  - Isoniazid preventive therapy in correctional facilities:  a systematic review.
AB  - Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide and
      the main cause of death in correctional facilities in middle- and low-income
      countries. Due to the closed environment and the concentration of individuals
      with TB-related risk factors, effective measures are required to control TB in
      such settings. Isoniazid preventive therapy (IPT) represents an effective and
      cost-effective measure. Despite international recommendations that IPT be
      integral to TB control, it is seldom deployed. A systematic review of
      interventions used to assess IPT initiation and completion in correctional
      facilities was conducted using published studies from two biomedical databases
      and relevant keywords. Additional references were reviewed, resulting in 18
      eligible studies. Most (72%) studies were conducted in the United States and in
      jail settings (60%), with the main objective of improving completion rates inside
      the facility or after release. Studies that provided data about initiation and
      completion rates showed poor success in correctional facilities. Adverse
      consequences and treatment interruption ranged from 1% to 55% (median 5%) in
      reported studies; hepatotoxicity was the most prevalent adverse reaction. Despite
      its accelerating effect on the development of active TB, information on human
      immunodeficiency virus (HIV) status was provided in only half of the studies.
      Among the four studies where IPT effectiveness was assessed, the results mirror
      those described in community settings. Future studies require thorough
      assessments of IPT initiation and completion rates and adverse effects,
      particularly in low- and middle-income countries and where comorbid viral
      hepatitis may contribute significantly to outcomes, and in settings where TB and
      HIV are more endemic.

PMID- 22410103
TI  - A randomised trial of nicotine assisted reduction to stop in pharmacies - the
      RedPharm study.
AB  - BACKGROUND: Public policy and clinical treatment in tobacco addiction in the UK
      has focused on cessation: an abrupt attempt to stop all cigarettes. However,
      recent evidence suggests that allowing more gradual withdrawal from tobacco or
      even permanent partial substitution by nicotine replacement therapy (NRT) could
      lead to net benefits to public health. No jurisdiction has introduced smoking
      reduction programmes in normal clinical care and the best methods for their
      implementation is uncertain. Community pharmacists offering smoking cessation
      services in the UK are ideally placed to implement reduction programmes.This
      pilot study aims therefore to examine the feasibility of implementing smoking
      reduction programme in pharmacies, and also to see if behavioural support and a
      longer treatment affect the success rate for cessation. DESIGN AND METHODS: This
      is a 2 * 2 randomised factorial trial of behavioural support versus no support
      and short versus standard length reduction programme. The pharmacists will
      recruit 16 patients per pharmacy, 160 smokers altogether. Pharmacists will
      randomise each participant by sealed envelopes. In a standard supported
      programme, the pharmacist will give support for 34 weeks, inviting participants
      to set a treatment goal and providing advice on how to reduce cigarette use.
      Participants in the short programme will be given the same advice on how to
      reduce but will reduce smoking over four weeks. Participants in the no support
      arms will be given a leaflet that describes the reduction programmes in 4-week
      and 34-week format. All participants are encouraged to use of NRT to support the
      reduction. These processes will be measured by recording the number of recruited
      smokers; percentage of those who reduce and sustain their consumption to at least
      50% of baseline value, and the proportion of people who attain 4 weeks abstinence
      and 6 months abstinence. Interviews will assess smokers' and pharmacists' views
      on the way the programme ran. DISCUSSION: This is a pilot study to assess the
      feasibility of offering smoking reduction programme within pharmacies that offer
      naturalistic setting to show population benefit from these programmes. Findings
      from this trial will inform the development of evidence-based treatment for
      smokers who want to reduce and best approaches to engage reluctant quitters onto
      the programme. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 2010-019259
      24.

PMID- 22410104
TI  - The song remains the same although the instruments are changing: complications
      following selective non-operative management of blunt spleen trauma: a
      retrospective review of patients at a level I trauma centre from 1996 to 2007.
AB  - BACKGROUND: Despite a widespread shift to selective non-operative management
      (SNOM) for blunt splenic trauma, there remains uncertainty regarding the role of
      adjuncts such as interventional radiological techniques, the need for follow-up
      imaging, and the incidence of long-term complications. We evaluated the success
      of SNOM (including splenic artery embolization, SAE) for the management of blunt
      splenic injuries in severely injured patients. METHODS: Retrospective review
      (1996-2007) of the Alberta Trauma Registry and health records for blunt splenic
      trauma patients, aged 18 and older, with injury severity scores of 12 or greater,
      admitted to the Foothills Medical Centre. RESULTS: Among 538 eligible patients,
      150 (26%) underwent early operative intervention. The proportion of patients
      managed by SNOM rose from 50 to 78% over the study period, with an overall
      success rate of SNOM of 87%, while injury acuity remained unchanged over time.
      Among SNOM failures, 65% underwent surgery within 24 hours of admission. Splenic
      arterial embolization (SAE) was used in only 7% of patients managed non
      operatively, although at least 21% of failed SNOM had contrast extravasation
      potentially amenable to SAE. Among Calgary residents undergoing SNOM, hospital
      readmission within six months was required in three (2%), all of whom who
      required emergent intervention (splenectomy 2, SAE 1) and in whom none had post
      discharge follow-up imaging. Overall, the use of post-discharge follow-up CT
      imaging was low following SNOM (10%), and thus no CT images identified occult
      hemorrhage or pseudoaneurysm. We observed seven cases of delayed splenic rupture
      in our population which occurred from five days to two months following initial
      injury. Three of these occurred in the post-discharge period requiring
      readmission and intervention. CONCLUSIONS: SNOM was the initial treatment
      strategy for most patients with blunt splenic trauma with 13% requiring
      subsequent operative intervention intended for the spleen. Cases of delayed
      splenic rupture occurred up to two months following initial injury. The low use
      of both follow-up imaging and SAE make assessment of the utility of these
      adjuncts difficult and adherence to formalized protocols will be required to
      fully assess the benefit of multi-modality management strategies.

PMID- 22410105
TI  - Reaching out and reaching up - developing a low cost drug treatment system in
      Cambodia.
AB  - Cambodia, confronted by the spread of drug misuse among young people, requested
      support from international agencies to develop a drug treatment programme in
      2000. The initial plan developed by the United Nations Office on Drugs and Crime
      was to set up a number of conventional drug treatment centres in urban areas.
      During the planning phase, however, the project was redesigned as a community
      based outreach programme. Ten Community Counselling Teams have been formed and
      trained in pilot areas, and within the first year of operation 462 drug and
      alcohol users contacted. Comprising former drug users, family members affected by
      drug use and health care staff, they have drug scene credibility, local knowledge
      and connectivity, and a rudimentary level of medical competence. Crucially, they
      enjoy the support of village elders, who are involved in the planning and
      reporting stages. While the Community Counselling Teams with their basic training
      in addiction counselling are in no position as yet to either provide or refer
      clients to treatment, they can provide brief interventions, organise self help
      groups, and most importantly provide an alternative to law enforcement. By taking
      a development centred approach, with emphasis on community, empowerment and
      inclusion, it provides a constructive and inclusive alternative to medical
      approaches and the compulsory drug treatment centres. The paper is based on an
      evaluation involving interviews with a range of stakeholders and a review of
      project documents.

PMID- 22410106
TI  - Establishing indices for groundwater contamination risk assessment in the
      vicinity of hazardous waste landfills in China.
AB  - Groundwater contamination by leachate is the most damaging environmental impact
      over the entire life of a hazardous waste landfill (HWL). With the number of HWL
      facilities in China rapidly increasing, and considering the poor status of
      environmental risk management, it is imperative that effective environmental risk
      management methods be implemented. A risk assessment indices system for HWL
      groundwater contamination is here proposed, which can simplify the risk
      assessment procedure and make it more user-friendly. The assessment framework and
      indices were drawn from five aspects: source term, underground media, leachate
      properties, risk receptors and landfill management quality, and a risk assessment
      indices system consisting of 38 cardinal indicators was established. Comparison
      with multimedia models revealed that the proposed indices system was integrated
      and quantitative, that input data for it could be easily collected, and that it
      could be widely used for environmental risk assessment (ERA) in China.

PMID- 22410107
TI  - Comparison of neuropsychological impairment and vocational outcomes in systemic
      lupus erythematosus and multiple sclerosis patients.
AB  - Systemic lupus erythematosus (SLE) and multiple sclerosis (MS) are chronic
      immunologic diseases that can cause cognitive dysfunction. MS is a central
      nervous system (CNS) disease characterized by demyelination and progressive brain
      atrophy. SLE is an autoimmune disease capable of damaging multiple organ systems,
      including the CNS. Cognitive disturbances are seen in both SLE and MS. The
      present study is concerned with understanding the similarities and differences
      between the cognitive profiles of SLE and MS as well as the relationship between
      cognitive impairment and vocational disability in these patients. We examined 47
      SLE patients, 47 MS patients, and 44 healthy controls. The groups were well
      matched on demographics and the patient groups were also matched on disease
      duration and severity. Group comparisons revealed that generative verbal fluency
      and visual-spatial memory are more profoundly affected in MS than SLE; whereas
      depression, fatigue, and working memory deficits are similarly involved in both
      diseases. Logistic regression analysis revealed that executive function, in
      particular, was predictive of vocational outcomes in SLE and MS patients.

PMID- 22410108
TI  - The essence on mass spectrometry based microbial diagnostics.
AB  - In recent years, matrix-assisted laser desorption/ionisation time-of-flight
      (MALDI-TOF) mass spectrometry has become an important bioanalytical method to
      detect profiles of proteins and peptides derived from whole bacterial cells. This
      accurate molecular-phenotypic method can be easily applied to robustly detect
      bacteria on the genus, species and in some cases on the subspecies level.
      Standardised laboratory protocols for the preparation of abundant bacterial
      proteins and the development of tailored data analysis software, as well as high
      quality databases of microbial reference mass spectra, made the procedure
      attractive to replace phenotypic or biochemical procedures for identification of
      bacteria and other microorganisms. Moreover, genotypic and functional mass
      spectrometry based methods to detect for example bacterial strains or antibiotic
      resistance may become useful in the coming years. In general, mass spectrometry
      is a powerful tool to facilitate routine microbial diagnostics.

PMID- 22410109
TI  - Cell regulation.

PMID- 22410110
TI  - Factors predicting the non-sentinel lymph node involvement in breast cancer
      patients with sentinel lymph node metastases.
AB  - OBJECTIVE: In a significant proportion of patients, the sentinel lymph node (SLN)
      is the only involved axillary node. The goal of the present study was to identify
      predictive factors associated with a positive SLN and with a positive non-SLN in
      patients in whom axillary lymph node dissection (ALND) was performed. METHODS:
      Data was reviewed for patients with T1-2 invasive breast cancer who underwent SLN
      biopsy with or without axillary dissection in a single institution between July
      2000 and May 2010. The SLNs were examined by serial sectioning and H&E staining,
      and by cytokeratin immunostaining in suspicious cases. RESULTS: Of 332 patients
      with SLNB, 134 had SLN positivity, and 116 of them further underwent completion
      axillary dissection. Patients with T2 tumors (OR=3.2; 95% CI, 1.74-5.58), or
      tumors with lymphovascular invasion (OR=8.0; 95% CI, 4.44-14.27), or invasive
      ductal cancer (OR=2.92; 95% CI, 1.1-8.0) were more likely to have a positive SLN.
      In patients with ALND, the non-SLN involvement rates were 10%, 11.5% and 50% in
      patients with isolated tumor cells (ITC), micrometastasis and macrometastasis,
      respectively. Finding of ITC or micrometastasis in SLNs (OR=0.28; 95% CI, 0.08
      0.99) or presence of extracapsular invasion (ECI) in SLN (OR=0.24; 95% CI, 0.09
      0.67) were the predictive factors of not having a non-SLN metastasis in logistic
      regression analysis. CONCLUSIONS: These findings suggest further axillary surgery
      can be best omitted in patients with micrometastasis while validation of
      nomograms including factors such as ECI are still needed to be studied in
      patients with macrometastasis.

PMID- 22410111
TI  - Primary chemo-radiotherapy in the treatment of locally advanced and inflammatory
      breast cancer.
AB  - BACKGROUND: The best management of large, diffuse or inflammatory breast cancers
      is uncertain and the place of radiotherapy and/or surgery is not clearly defined.
      METHODS: A cohort of 123 patients with non-metastatic locally advanced or
      inflammatory breast cancer 3 cm or more in diameter or T4, was treated between
      1989 and 2006. All patients received primary chemotherapy followed by
      radiotherapy, 40 Gy in 15 fractions with 10 Gy boost. Patients with ER positive
      tumours received Tamoxifen. Assessment was carried out 8 weeks post-treatment and
      surgery was reserved for residual or recurrent disease. RESULTS: For each stage
      there were T2/3: 63, T4b: 31 and T4d: 29 patients. 80 had complete clinical
      response (65%) but 18 patients were never free of inoperable local disease. 25
      patients had residual operable disease at assessment and 12 patients who
      initially had a complete response developed operable local recurrence (LR). 37
      Patients (30%) had surgery at a mean of 15 months post diagnosis. At 5 years,
      overall survival (OS) of the two surgical groups was not significantly different
      from those 68 patients who had complete remission without surgery, p=0.218, HR
      1.46 (0.80-2.55). Surgery as an independent variable to predict survival was not
      significant on a Cox proportional hazards model (p=0.97). LR in the surgical
      groups was 13.5% vs 17.5% in the non-surgical patients. The median OS was 64.5
      months and disease-free survival (DFS) was 52.5 months. 5-Year OS was 54% and DFS
      survival 43%. CONCLUSION: In patients with a complete or partial response to
      chemo-radiotherapy for locally advanced or inflammatory breast cancer, reserving
      surgery for those with residual or recurrent local disease did not appear to
      compromise survival. This finding would support examination of this treatment
      strategy by a randomised controlled trial.

PMID- 22410112
TI  - The microstructure and surface morphology of radiopaque tricalcium silicate
      cement exposed to different curing conditions.
AB  - OBJECTIVE: Tricalcium silicate is the major constituent phase in mineral trioxide
      aggregate (MTA). It is thus postulated that pure tricalcium silicate can replace
      the Portland cement component of MTA. The aim of this research was to evaluate
      the microstructure and surface characteristics of radiopaque tricalcium silicate
      cement exposed to different curing conditions namely at 100% humidity or immersed
      in either water or a simulated body fluid at 37 degrees C. METHODS: The materials
      under study included tricalcium silicate and Portland cements with and without
      the addition of bismuth oxide radiopacifier. Material characterization was
      performed on hydrated cements using a combination of scanning electron microscopy
      (SEM) with X-ray energy dispersive (EDX) analyses and X-ray diffraction (XRD)
      analyses. Surface morphology was further investigated using optical profilometry.
      Testing was performed on cements cured at 100% humidity or immersed in either
      water or Hank's balanced salt solution (HBSS) for 1 and 28 days at 37 degrees C.
      In addition leachate analysis was performed by X-ray fluorescence of the storage
      solution. The pH of the storage solution was assessed. RESULTS: All the cements
      produced calcium silicate hydrate and calcium hydroxide on hydration. Tricalcium
      silicate showed a higher reaction rate than Portland cement and addition of
      bismuth oxide seemed to also increase the rate of reaction with more calcium
      silicate hydrate and calcium hydroxide being produced as demonstrated by SEM and
      XRD analysis and also by surface deposits viewed by the optical profilometer.
      Cement immersion in HBSS resulted in the deposition of calcium phosphate during
      the early stages following immersion and extensive calcification after 28 days.
      The pH of all storage solutions was alkaline. The immersion in distilled water
      resulted in a higher pH of the solution than when the cements were immersed in
      HBSS. Leachate analysis demonstrated high calcium levels in all cements tested
      with higher levels in tricalcium silicate and bismuth replaced cements.
      SIGNIFICANCE: Tricalcium silicate cement is more bioactive than Portland cement
      as demonstrated by various characterization techniques. The bioactivity was
      monitored by measuring the production of calcium hydroxide and the formation of
      calcium phosphate when in contact with simulated body fluids.

PMID- 22410113
TI  - Three years in vivo wear: core-ceramic, veneers, and enamel antagonists.
AB  - OBJECTIVES: Test the hypotheses that there are equivalent wear rates for enamel
      versus-enamel and ceramic-versus-enamel, analyzing the in vivo wear of crown
      ceramics, their natural enamel antagonists, and the corresponding two
      contralateral teeth; and, that bite force does not correlate with the wear.
      METHODS: A controlled, clinical trial was conducted involving patients needing
      full coverage crowns opposing enamel antagonists. Bite forces were measured using
      a bilateral gnathodynamometer. Single-unit restorations of metal/ceramic
      (Argedent 62, Argen Corp/IPS d.SIGN veneer); or, core-ceramic/veneer from either,
      Empress2/Eris, or e.max Press core/e.max Ceram glaze (ceramics: Ivoclar Vivadent,
      USA) were randomly assigned, fabricated and cemented. Impressions were made of
      the ceramic crowns, as well as each maxillary and mandibular quadrant at one week
      (baseline) and one, two and three years. Resulting models were scanned (3D laser
      scanner). Maximum wear was calculated by superimposing baseline with annual
      images. RESULTS: There were a total of thirty-six crowns required for thirty-one
      patients. Each restoration had three associated enamel teeth: crown, (1)
      antagonist, (2) contralateral and (3) contralateral-antagonist. SAS PROC MIXED
      (alpha=0.05) indicated no statistical significance for mean maximum wear among
      crown ceramics, enamel antagonists and contralaterals. However, enamel wear was
      statistically significant in relation to intraoral location (p=0.04) and among
      years (p<0.02). Analyzed alone, the enamel contralateral-antagonist exhibited
      significantly greater wear (p<0.001). Considering all wear sites, there was no
      correlation with bite force (p=0.15). SIGNIFICANCE: The ceramics and their
      antagonists exhibited in vivo wear rates within the range of normal enamel.
      Future studies should examine the wear implications of the contralateral
      antagonist enamel.

PMID- 22410114
TI  - Novel cathepsin B-sensitive paclitaxel conjugate: Higher water solubility, better
      efficacy and lower toxicity.
AB  - In order to realize the targeted delivery of paclitaxel (PTX) to tumor through an
      environment-sensitive mechanism, increase its solubility in water and reformulate
      without toxic excipients, a novel PTX conjugate, PEG-VC-PABC-PTX was designed and
      synthesized in this study, using p-aminobenzylcarbonyl (PABC), a spacer, and
      valine-citrulline (VC), a substrate of cathepsin B (C(B)), to link polyethylene
      glycol (PEG) and PTX. Pegylated PTX (PEG-PTX) which was synthesized and Taxol
      formulation were prepared as controls. The conjugates were purified and
      characterized by melting points, (1)H-NMR, ESI-MS or MALDI-TOF-MS. The two
      conjugates were similar in particle size, water solubility and their effects on
      MCF-7 cell line in vitro, and both of them induced no obvious toxicity in vivo.
      The release of PTX from PEG-PTX was faster due to its ester bond, while PEG-VC
      PABC-PTX was proved to be C(B)-sensitive in terms of PTX release and its effect
      on cell cycle. Additionally, PEG-VC-PABC-PTX exhibited significant effects of
      antitumor, anti-angiogenesis and anti-proliferation in vivo, while the control
      conjugate was almost inefficacious at the same in vivo test. On the other hand,
      PTX conjugates demonstrated a thousand-time or more improvement in water
      solubility compared to PTX, suggesting a very easy way in the preparation and use
      of its injection. Without involvement of Cremophore EL and ethanol, the PTX
      conjugate will guarantee less adverse effects as frequently reported for Taxol
      formulation. Taxol formulation had a higher cytoxicity in vitro than PEG-VC-PABC
      PTX likely because of toxic additives. Importantly, the C(B)-sensitive conjugate
      indicated a similar in vivo efficacy with the Taxol control, but much lower in
      vivo toxicity at the same doses evidenced by body weight, animal status, liver
      toxicity and blood count. Moreover, at the tolerant dose, this novel conjugate
      exhibited significantly better antitumor effect than that of Taxol formulation.
      In general, the PEG-VC-PABC-PTX conjugate designed in this study demonstrated
      significant advantages in terms of high water solubility, no toxic surfactant or
      organic solvent, tumor environment-sensitivity and high therapeutic index.

PMID- 22410115
TI  - Co-delivery of TRAIL gene enhances the anti-glioblastoma effect of paclitaxel in
      vitro and in vivo.
AB  - Co-delivery of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      and paclitaxel (PTX) is an attractive strategy to enhance their anti-tumor
      efficacy. As the most aggressive brain tumor, glioblastoma is sensitive to TRAIL
      and PTX. However, their therapeutic efficacy for intracranial glioblastoma is
      significantly impaired by blood-brain barrier (BBB) and blood-tumor barrier
      (BTB). Previously, we have prepared c(RGDyK)-poly(ethylene glycol)
      polyethyleneimine (RGD-PEG-PEI) as a non-viral gene carrier for glioblastoma
      targeted therapy by employing a cyclic RGD peptide (c(RGDyK), cyclic arginine
      glycine-aspartic acid-d-tyrosine-lysine), which binds to integrin alpha(v)beta(3)
      over-expressed neovasculature and U87 glioblastoma cells with high affinities. In
      the present work, it was found that low concentration of paclitaxel (10nM)
      significantly enhanced the gene transfection of RGD-PEG-PEI/pDNA nanoparticle,
      which, in turn, dramatically elevated the anti-glioblastoma effect of paclitaxel
      in vitro. The gene transfection was also elevated in vivo. Co-delivery of brain
      targeted CDX-PEG-PLA-PTX micelle dramatically enhanced gene transfection
      efficiency in the intracranial brain tumor. Due to the change of BBB integrity
      and the formation of BTB, we subsequently investigated the anti-glioblastoma
      effects of RGD-PEG-PEI/pORF-hTRAIL nanoparticle combined with CDX-PEG-PLA-PTX
      micelle (paclitaxel loaded CDX-poly(ethylene glycol)-block-poly(lactic acid)
      micelle). While at the same dosages, the median survival of the intracranial
      glioblastoma-bearing model mice treated with co-delivery (33.5 days) is
      significantly longer than those of solely treated mice with CDX-PEG-PLA-PTX (25.5
      days), RGD-PEG-PEI/pORF-hTRAIL (24.5 days) or physiological saline (21.5 days).
      Herein, we verify the high potency of co-delivery of TRAIL gene and paclitaxel in
      the intervention of intracranial glioblastoma by employing tumor-targeted gene
      carrier RGD-PEG-PEI and brain-targeted micelle CDX-PEG-PLA, respectively.

PMID- 22410116
TI  - Bioactive hydrogels demonstrate mediated release of a chromophore by
      chymotrypsin.
AB  - A model system, alpha-chymotrypsin (Cht) (a protease) and a cleavable peptide
      chromogen (pro-drug) covalently incorporated into a hydrogel, was investigated to
      understand the mechanisms of covalent loading and release by enzymatic cleavage
      in bio-responsive delivery systems. Using EDC and Sulfo-NHS, terminal carboxyl
      groups of N-succinyl-Ala-Ala-Pro-Phe p-nitroanilide, a cleavable chromogen, were
      conjugated to primary amines of a hydrated poly(HEMA)-based hydrogel. Hydrogel
      disks were incubated in buffered Cht causing enzyme-mediated cleavage of the
      peptide and concomitant release of the chromophore for monitoring. To investigate
      substrate loading and the effects of hydrogel morphology on the system, the
      concentration of the amino groups (5, 10, 20, and 30 mol%) and the cross-linked
      density (1, 5, 7, 9 and 12 mol%) were independently varied. Loading-Release
      Efficiency of the chromogen was shown to exhibit a positive relation to
      increasing amino groups (AEMA). The release rates demonstrated a negative
      relation to increasing cross-linked density attributed to decreasing void
      fractions and increasing tortuosities. The diffusion coefficient of Cht,
      D(0,Cht), was determined to be 6.9+/-0.5*10(-7)cm(2)s(-1), and the range of
      D(eff) of Cht for 1 to 12 mol% TEGDA was determined to be 6.9*10(-8) to 0.1*10(
      8)cm(2)s(-1). We show how these parameters may be optimized and used to achieve
      programmed release rates in engineered bio-responsive systems.

PMID- 22410117
TI  - Rottlerin induces apoptosis of HT29 colon carcinoma cells through NAG-1
      upregulation via an ERK and p38 MAPK-dependent and PKC delta-independent
      mechanism.
AB  - Rottlerin, a selective inhibitor of novel isoforms of protein kinase C delta (PKC
      delta), has been shown to exert multiple effects on cancer cells, including
      inhibition of cell proliferation and migration. However, the molecular mechanisms
      responsible for these effects are not fully understood. We found that rottlerin
      dramatically induced non-steroidal anti-inflammatory drug activated gene-1 (NAG
      1) expression in both p53 wild-type and p53-null cancer cell lines, suggesting
      that NAG-1 upregulation is a common response to rottlerin that occurs
      independently of p53 in multiple cell lines. Although rottlerin is known to
      inhibit PKC delta, PKC delta siRNA and overexpression of dominant-negative (DN)
      PKC delta did not affect rottlerin-mediated induction of NAG-1. These results
      suggest that rottlerin induces NAG-1 upregulation via a PKC delta-independent
      pathway. We also observed that CHOP protein levels were significantly increased
      by rottlerin, but CHOP siRNA did not affect rottlerin-induced NAG-1 expression.
      In addition, we demonstrated the involvement of the mitogen-activated protein
      kinase (MAP kinase) signal transduction pathway in rottlerin-induced NAG-1
      expression. Inhibitors of MEK (PD98059) and p38 MAP kinase (SB203580) prevented
      rottlerin-induced NAG-1 expression. Furthermore, we found that down-regulation of
      NAG-1 attenuated rottlerin-induced apoptosis. Collectively, the results of this
      study demonstrate, for the first time, that upregulation of NAG-1 contributes to
      rottlerin-induced apoptosis in cancer cells.

PMID- 22410118
TI  - 1,3-Diphenylpropenone ameliorates TNBS-induced rat colitis through suppression of
      NF-kappaB activation and IL-8 induction.
AB  - In the present study, we examined whether newly synthesized phenylpropenone
      derivatives, by inhibiting NF-kappaB activity, would inhibit IL-8 expression,
      inflammation and abnormal angiogenesis, resulting in amelioration of disease
      conditions. The phenylpropenone derivatives inhibited NF-kappaB transcriptional
      activity, which correlated with their suppressive activity against TNF-alpha
      induced adhesion of U937 human monocytic cells to HT-29 human colonic epithelial
      cells, an in vitro model of IBD. Among the derivatives, 1,3-diphenylpropenone
      (DPhP) was most efficacious, and it significantly suppressed TNF-alpha-induced
      production of IL-8 which is a proinflammatory and proangiogenic cytokine. The
      anti-inflammatory activity of DPhP was also confirmed in the trinitrobenzene
      sulfonic acid (TNBS)-induced rat colitis model. DPhP was protective against the
      TNBS-induced inflammatory responses, which included weight loss, increased
      myeloperoxidase activity and mucosal damage. In the colon tissue, DPhP inhibited
      TNBS-induced NF-kappaB nuclear translocation, IL-8 and TNF-alpha expressions, and
      abnormal angiogenesis. In addition, DPhP also suppressed IL-8-induced
      angiogenesis, which was revealed by an in vivo assay using chick chorioallantoic
      membrane. Furthermore, the level of IL-6, a pleiotropic cytokine which is
      implicated in the pathogenesis of IBD and colitis-associated cancer, was
      suppressed by DPhP in rat colon tissue and serum. In conclusion, the results
      suggest that DPhP is a potential dual-acting IBD drug candidate targeting both
      inflammation and abnormal angiogenesis, possibly through the NF-kappaB and IL-8
      signaling pathway.

PMID- 22410119
TI  - Prediction of pork quality with near infrared spectroscopy (NIRS): 1. Feasibility
      and robustness of NIRS measurements at laboratory scale.
AB  - The objective was to study prediction of pork quality by near infrared
      spectroscopy (NIRS) technology in the laboratory. A total of 131 commercial pork
      loin samples were measured with NIRS. Predictive equations were developed for
      drip loss %, colour L*, a*, b* and pH ultimate (pHu). Equations with R(2)>0.70
      and residual prediction deviation (RPD)>=1.9 were considered as applicable to
      predict pork quality. For drip loss% the prediction equation was developed (R(2)
      0.73, RPD 1.9) and 76% of those grouped superior and inferior samples were
      predicted within the groups. For colour L*, test-set samples were predicted with
      R(2) 0.75, RPD 2.0, colour a* R(2) 0.51, RPD 1.4, colour b* R(2) 0.55, RPD 1.5
      and pHu R(2) 0.36, RPD 1.3. It is concluded that NIRS prediction equations could
      be developed to predict drip loss% and L*, of pork samples. NIRS equations for
      colour a*, b* and pHu were not applicable for the prediction of pork quality on
      commercially slaughtered pigs.

PMID- 22410120
TI  - Indoleamine 2,3-dioxygenase expression in patients with allergic rhinitis: a case
      control study.
AB  - BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan catalyzing enzyme.
      It has been suggested that it has a role in lower airway allergic inflammations,
      but its role in allergic rhinitis has not been investigated. OBJECTIVE: Our aim
      was to evaluate the expression of IDO in the nasal mucosa of allergic rhinitis
      patients allergic to birch pollen during peak exposure to birch pollen allergen
      and compare it to non-atopic patients. METHODS: IDO expression was
      immunohistochemically evaluated from nasal specimens obtained in- and off-season
      from otherwise healthy non-smoking volunteers both allergic to birch pollen
      (having mild or moderate allergic rhinoconjunctivitis) and non-allergic controls.
      RESULTS: The IDO expression levels were low in healthy controls and remained low
      also in patients allergic to birch pollen. There were no differences in the
      expression of IDO in- and off-season in either healthy or allergic subjects.
      CONCLUSIONS: There is a controversy in the role of IDO in upper and lower airways
      during allergic airway disease. It seems that IDO is associated to allergic
      inflammations of the lower airways, but does not have a local role in the nasal
      cavity at least in mild or moderate forms of allergic rhinitis.

PMID- 22410121
TI  - Lack of association between asymmetric dimethylarginine and in vivo microvascular
      and macrovascular endothelial function in patients with rheumatoid arthritis.
AB  - OBJECTIVES: The aim of the present study was to investigate if assymetric
      dimethylarginine (ADMA) is increased in patients with rheumatoid arthritis (RA)
      compared to healthy controls and to examine associations between ADMA, RA disease
      activity and in vivo assessments of microvascular and macrovascular endothelial
      function. METHODS: Sixty-seven RA patients (age [mean +/- standard deviation]: 56
      +/- 12 years, disease duration median [25th-75th percentile]: 8 [3-15] years, 48
      women) and 29 healthy controls (age [mean +/- standard deviation]: 42 +/- 12, 21
      women) underwent assessments of microvascular endothelial function (Laser Doppler
      imaging with iontophoresis of acetylcholine and sodium-nitroprusside), and
      macrovascular endothelial function (flow-mediated dilatation and glyceryl
      trinitrate-mediated dilatation) as well as arterial stiffness. ADMA levels were
      measured in contemporary specimens using an immunoassay ELISA kit. RESULTS: ADMA
      levels were significantly higher (p=0.004) in RA patients compared with healthy
      controls after adjustment for age (difference=0.088, 95% confidence interval
      0.029-0.147). ADMA levels did not correlate with demographic or disease
      characteristics. No correlation was found between ADMA and microvascular and
      macrovascular endothelial function or with arterial stiffness. CONCLUSIONS: ADMA
      levels are increased in patients with RA but there was no significant correlation
      with in vivo assessments of endothelial function. Further studies are needed to
      unfold the pathophysiological role of nitric oxide/ADMA pathway derangement in
      endothelial dysfunction and cardiovascular risk in RA.

PMID- 22410122
TI  - A combination of secondhand cigarette smoke and Chlamydia pneumoniae accelerates
      atherosclerosis.
AB  - OBJECTIVE: Secondhand smoke (SS) induces chronic infection of endothelial cells
      by Chlamydia pneumoniae (Cpn) in vitro. We investigated the in vivo effect on
      atherosclerosis following exposure to SS and infection with Cpn both
      independently and in combination in ApoE-/- mice. METHODS AND RESULTS: Plaques
      were largest in the combined SS+Cpn-exposed mice with 12-57% greater cross
      sectional area compared with all other groups (P<0.03). Quantitative RT-PCR (qRT
      PCR) from aortic roots revealed a synergistic upregulation of both OX40L (CD134L)
      and MyD88 in SS+Cpn mice (P<0.05). This upregulation occurred despite decreased
      numbers of macrophage, dendritic cell, CD4 T cell and smooth-muscle-cell
      infiltrates as determined by quantitative IHC and qRT-PCR. To elucidate whether
      enhanced apoptosis correlated with reduced plaque cellularity, area of Tdt
      mediated dUTP nick labeling positive (TUNEL+) cells and expression of key
      bridging molecules necessary for efferocytosis (Mertk, Tgm2, FasL and C1qa) were
      examined. In SS+Cpn mice, there was an increase of the area of TUNEL+ cells in
      plaque cores (P<0.001) and a downregulation of efferocytosis gene expression
      (P<0.05). Systemic expression of cytokines in sera (Luminex) showed no
      differences between groups, suggesting that focal disease mechanisms within the
      plaque predominated. CONCLUSIONS: The combination of SS exposure and Cpn
      infection enhanced atherosclerosis more than either variable did independently by
      activating inflammatory cells and by promoting growth and maturation of lesions
      via defective phagocytic clearance and accumulation of apoptotic cells.

PMID- 22410123
TI  - Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and
      identification of factors associated with treatment response: a pooled analysis
      of over 21,000 subjects from 27 clinical trials.
AB  - OBJECTIVE: Patients with dyslipoproteinemia constitute the largest risk group for
      development of atherosclerosis and cardiovascular disease (CVD). Despite
      extensive statin use, many patients with CVD risk do not achieve guideline
      recommended low-density lipoprotein cholesterol (LDL-C) targets. This pooled
      analysis of 27 previously published clinical trials conducted between 1999 and
      2008 evaluated the lipid-altering efficacy and factors related to treatment
      response of ezetimibe combined with statin and statin monotherapy. METHODS:
      Patient-level data were combined from double-blind, placebo-controlled or active
      comparator studies randomizing adult subjects to ezetimibe 10mg plus statin
      (n=11,714) versus statin alone (n=10,517) for 6-24 weeks (mean=9 weeks).
      Association of factors with treatment response, percent change from baseline LDL
      C and other lipids, and attainment of guideline-recommended lipid and lipoprotein
      targets were evaluated. RESULTS: Higher baseline LDL-C, diabetes mellitus, Black
      race, greater age, and male gender were associated with small but significantly
      greater percent reductions in LDL-C regardless of treatment. Treatment influenced
      efficacy, with ezetimibe plus statin producing significantly greater reductions
      in LDL-C, total-cholesterol, non-HDL-C, ApoB, triglycerides, lipid ratios, hs
      CRP; significantly larger increases in HDL-C and ApoA1; and significantly higher
      achievement of LDL-C (<70mg/dl, <100mg/dl), non-HDL-C (<100mg/dl, <130mg/dl), and
      ApoB (<80mg/dl, <90mg/dl) targets than statin monotherapy at statin potencies
      compared (p<0.0001 for all). Differential treatment effects were seen with first
      /second-line therapy and statin potency. CONCLUSION: These results suggest that
      patient characteristics have a limited influence on response to lipid-lowering
      therapy and demonstrate the consistent treatment effect of ezetimibe combined
      with statin and statin monotherapy across a diverse patient population.

PMID- 22410124
TI  - Coronary plaque rupture in patients with myocardial infarction after noncardiac
      surgery: frequent and dangerous.
AB  - PURPOSE: The pathophysiology of acute coronary syndromes (ACS) after noncardiac
      surgery is not established yet. Thrombosis over a vulnerable plaque or decreased
      oxygen supply secondary to anemia or hypotension may be involved. The purpose of
      this study was to investigate the pathophysiology of ACS complicating noncardiac
      surgery. METHODS: Clinical and angiographic data were prospectively recorded into
      a database for 120 consecutive patients that had an ACS after noncardiac surgery
      (PACS), for 120 patients with spontaneous ACS (SACS), and 240 patients with
      stable coronary artery disease (CAD). Coronary lesions with obstructions greater
      than 50% were classified based on two criteria: Ambrose's classification and
      complex morphology. The presence of Ambrose's type II or complex lesions were
      compared between the three groups. RESULTS: We analyzed 1470 lesions in 480
      patients. In PACS group, 45% of patients had Ambrose's type II lesions vs. 56.7%
      in SACS group and 16.4% in stable CAD group (P<0.001). Both PACS and SACS
      patients had more complex lesions than patients in stable CAD group (56.7% vs.
      79.2% vs. 31.8%, respectively; P<0.001). Overall, the independent predictors of
      plaque rupture were being in the group PACS (P<0.001, OR 2.86; CI, 1.82-4.52 for
      complex lesions and P<0.001, OR 3.43; CI, 2.1-5.6 for Ambrose's type II lesions)
      or SACS (P<0.001, OR 8.71; CI, 5.15-14.73 for complex lesions and P<0.001, OR
      5.99; CI, 3.66-9.81 for Ambrose's type II lesions). CONCLUSIONS: Nearly 50% of
      patients with perioperative ACS have evidence of coronary plaque rupture,
      characterizing a type 1 myocardial infarction.

PMID- 22410126
TI  - Anger expression in Swiss adolescents: establishing measurement invariance across
      gender in the AX scales.
AB  - The present study examined measurement invariance in the three anger expression
      subscales of the STAXI (Spielberger, 1988) with respect to gender. In a sample of
      576 male and 531 female students, strict measurement invariance was found. For
      all three anger expression factors, no differences in variances or factor
      correlations were found. A large negative relation between Anger-Out and Anger
      Control emerged. Girls reported significantly lower levels in Anger-Out and Anger
      Control than boys. Results suggest that the questionnaire functions the same way
      across gender. Also, boys and girls exhibited the same range of interindividual
      differences in anger expression. The negative relation between Anger-Out and
      Anger-Control suggests that high levels of Anger-Out might be an obstacle in
      controlling anger. Lower levels of Anger-Out and -Control in girls suggest that
      girls might need less control because they express anger less outwardly.

PMID- 22410125
TI  - Silencing of HSulf-2 expression in MCF10DCIS.com cells attenuate ductal carcinoma
      in situ progression to invasive ductal carcinoma in vivo.
AB  - INTRODUCTION: Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous
      group of proliferative cellular lesions that have the potential to become
      invasive. Very little is known about the molecular alterations involved in the
      progression from DCIS to invasive ductal carcinoma (IDC). Heparan endosulfatase
      (HSulf-2) edits sulfate moieties on heparan sulfate proteoglycans (HSPGs) and has
      been implicated in modulating heparin binding growth factor signaling,
      angiogenesis and tumorigenesis. However, the role of HSulf-2 in breast cancer
      progression is poorly understood. MCF10DCIS.com cells (referred as MCF10DCIS)
      express HSulf-2 and form comedo type DCIS and progress to IDC when transplanted
      in immune-deficient mice and, therefore, is an ideal model to study breast cancer
      progression. We evaluated the role of HSulf-2 in progression from DCIS to IDC
      using mouse fat pad mammary xenografts. METHODS: Non-target control (NTC) and
      HSulf-2 knockdown in MCF10DCIS breast cancer cells were achieved by NTC shRNA and
      two different lentiviral shRNA against HSulf-2 respectively. Xenografts were
      established by injecting NTC and HSulf-2 deficient MCF10DCIS cells in mouse
      mammary fat pads. Xenografts were subjected to H&E staining for morphological
      analysis, TUNEL and Propidium iodide staining (to determine the extent of
      apoptosis), Western blot analysis and zymography. RESULTS: Using a mouse mammary
      fat pad derived xenograft model, we observed that compared to control treated
      xenografts, down-regulation of HSulf-2 was associated with significant delays in
      growth at Week 7 (P-value < 0.05). Histological examination of the tumors
      demonstrated substantial differences in comedo necrosis, with marked luminal
      apoptosis and up-regulation of apoptotic markers Bim, cleaved PARP and cleaved
      caspase 3 in HSulf-2 depleted xenografts. Furthermore, HSulf-2 depleted
      xenografts retained the basement membrane integrity with decreased activity and
      expression of matrix metalloproteinase 9 (MMP-9), an enzyme critical for
      degradation of extracellular matrix compared to nontargeted control. CONCLUSION:
      Our data suggest that HSulf-2 expression may be critical for human breast cancer
      progression. Down-regulation of HSulf-2 leads to retention of comedo type DCIS
      and delays the progression of DCIS to IDC. Further studies are necessary to
      determine if therapeutic targeting of HSulf-2 expression might delay the
      progression of DCIS to IDC.

PMID- 22410127
TI  - Condylar subchondral formation of cortical bone in adolescents and young adults.
AB  - We investigated subchondral formation of cortical bone in the condyles of
      adolescents and young adults, and looked for age-related and sex-related
      differences in bony formation with the aid of cone-beam computed tomography data
      in 1438 subjects aged between 10 and 30 years. The scans were part of the
      hospital's clinical protocol for patients seeking orthodontic or orthognathic
      treatment. No patient had signs or symptoms of temporomandibular disorders.
      Central images of the coronal and sagittal planes of the condyle were acquired
      and scored. Subchondral formation of cortical bone was seen as a high-density
      compact linear image, and subjects were classified into complete, partial, and no
      formation. Subchondral formation of cortical bone was first seen at the ages of
      13-14 in boys and 12-13 in girls. Complete cortical bony formation was seen after
      the age of 22 years for men and 21 for women. We conclude that cortical bone
      begins to form around the periphery of the condyles during adolescence (12-14
      years). A continuous, homogeneous, and compact cortical bony layer is established
      in young adults by the age of 21-22, indicating full development of the
      mandibular condyle. The condylar bone developed gradually and was generally fully
      developed a year earlier in women than men.

PMID- 22410128
TI  - Learning anatomy - a pain in the neck?

PMID- 22410129
TI  - Post-operative gait analysis in total hip replacement patients-a review of
      current literature and meta-analysis.
AB  - Gait analysis has been used to measure gait adaptations following total hip
      replacement (THR) for many years. In this time, advances have been made in
      implant technology and surgical procedure. However, gait adaptations persist
      after surgery. This review of seven published studies, where gait characteristics
      were compared between post-operative THR patients and healthy controls, had the
      objective of investigating current practice in gait analysis of this patient
      population and to determine if there is a consensus on post-operative gait
      changes associated with THR. Levels of methodological quality and study design
      were found to be variable. Meta-analyses were performed on all gait variables
      reported by at least three studies to determine overall Cohen's d effect sizes
      and 95% confidence intervals. Reductions in walking velocity (d=-0.79; CI=-1.54, 
      0.04), stride length (d=-1.06; CI=-1.62, -0.49) and sagittal hip range of motion
      (d=-1.58; CI=-2.12, -1.04) were observed. Increases in peak hip flexion (d=0.52;
      CI=-0.01, 1.09) and extension (d=0.54; CI=-0.10, 1.09) moments were found,
      although these were likely to be of less clinical significance. Reduced peak hip
      abduction was also observed (d=-0.58; CI=-1.09, -0.06). Future developments in
      THR technology and surgical methods should therefore aim to reduce the
      differences between patients and controls in terms of walking velocity, stride
      length, hip range of motion and hip abduction moments.

PMID- 22410130
TI  - Quantifying individual muscle contribution to three-dimensional reaching tasks.
AB  - We investigated the individual muscle contribution to arm motion to better
      understand the complex muscular coordination underlying three-dimensional (3D)
      reaching tasks of the upper limb (UL). The individual contributions of biceps,
      triceps, deltoid anterior, medius, posterior and pectoralis major to the control
      of specific degrees of freedom (DOFs) were examined: using a scaled
      musculoskeletal model, the muscle excitations that reproduce the kinematics were
      calculated using computed muscle control and a forward simulation was generated.
      During consequent perturbation analyses, the muscle excitation of selected
      muscles was instantaneously increased and the resulting effect on the specific
      DOF was studied to quantify the muscle contribution. The calculated muscle
      contributions were compared to the responses elicited during electrical
      stimulation experiments. Innovative in our findings is that muscle action during
      reaching clearly depended on the reaching trajectory in 3D space. For the
      majority of the muscles, the magnitude of muscle action changed and even reversed
      when reaching to different heights and widths. Furthermore, muscle effects on non
      spanned joints were reported. Using a musculoskeletal model and forward
      simulation techniques, we demonstrate individual position-dependent muscle
      contributions to 3D joint kinematics of the UL.

PMID- 22410131
TI  - Separate hydrolysis and co-fermentation for improved xylose utilization in
      integrated ethanol production from wheat meal and wheat straw.
AB  - BACKGROUND: The commercialization of second-generation bioethanol has not been
      realized due to several factors, including poor biomass utilization and high
      production cost. It is generally accepted that the most important parameters in
      reducing the production cost are the ethanol yield and the ethanol concentration
      in the fermentation broth. Agricultural residues contain large amounts of
      hemicellulose, and the utilization of xylose is thus a plausible way to improve
      the concentration and yield of ethanol during fermentation. Most naturally
      occurring ethanol-fermenting microorganisms do not utilize xylose, but a
      genetically modified yeast strain, TMB3400, has the ability to co-ferment glucose
      and xylose. However, the xylose uptake rate is only enhanced when the glucose
      concentration is low. RESULTS: Separate hydrolysis and co-fermentation of steam
      pretreated wheat straw (SPWS) combined with wheat-starch hydrolysate feed was
      performed in two separate processes. The average yield of ethanol and the xylose
      consumption reached 86% and 69%, respectively, when the hydrolysate of the
      enzymatically hydrolyzed (18.5% WIS) unwashed SPWS solid fraction and wheat
      starch hydrolysate were fed to the fermentor after 1 h of fermentation of the
      SPWS liquid fraction. In the other configuration, fermentation of the SPWS
      hydrolysate (7.0% WIS), resulted in an average ethanol yield of 93% from
      fermentation based on glucose and xylose and complete xylose consumption when
      wheat-starch hydrolysate was included in the feed. Increased initial cell density
      in the fermentation (from 5 to 20 g/L) did not increase the ethanol yield, but
      improved and accelerated xylose consumption in both cases. CONCLUSIONS: Higher
      ethanol yield has been achieved in co-fermentation of xylose and glucose in SPWS
      hydrolysate when wheat-starch hydrolysate was used as feed, then in co
      fermentation of the liquid fraction of SPWS fed with the mixed hydrolysates.
      Integration of first-generation and second-generation processes also increases
      the ethanol concentration, resulting in a reduction in the cost of the
      distillation step, thus improving the process economics.

PMID- 22410132
TI  - Differential decay kinetics of human cytomegalovirus glycoprotein B genotypes
      following antiviral chemotherapy.
AB  - BACKGROUND: The impact of different cytomegalovirus (HCMV) glycoprotein B (gB)
      genotypes on pathogenesis remains controversial. OBJECTIVES: To investigate the
      effect of gB genotypes either as single infections or as part of multiple
      infections on the early kinetics of response to ganciclovir therapy. METHODS:
      Patients (n=239) enrolled in a study of intravenous ganciclovir or valganciclovir
      for the treatment of HCMV disease were analysed by a gB genotype specific PCR to
      quantify the amount of each gB genotype present at initiation of therapy
      (baseline, day 0) and at days 3, 7, 14 and 21 post therapy. RESULTS AND
      CONCLUSIONS: In all gB groups (individual gB genotype infections and mixed
      genotype infections) there was a biphasic decline in viral load after therapy.
      The first phase half life (days 0-3) was <=1 day and was followed over the next
      18 days by a slower second phase decline with half lives ranging from 3.4 to 4.4
      days. The 1st phase rapid decline in viral load was dependent upon gB genotype
      whereas the ultimate viral load reduction at day 21 was relatively insensitive to
      gB genotype. A strong correlation between 1st phase decline and extent of viral
      load reduction at day 21 was observed (r=0.37; p=0.002). These data imply that
      early reductions in HCMV load after therapy may be useful in predicting the
      duration of drug therapy needed to control HCMV replication.

PMID- 22410133
TI  - Increased frequency of rotavirus G3P[8] and G12P[8] in Argentina during 2008
      2009: whole-genome characterization of emerging G12P[8] strains.
AB  - BACKGROUND: Group A rotaviruses are the leading cause of non-bacterial severe
      diarrhea disease in infants and young children. In humans, the most common
      genotypes are G1-G4 and G9. Recently, G12 strains have been sporadically reported
      in several countries, including Argentina, Brazil and Paraguay. OBJECTIVES: To
      analyze rotavirus strain diversity in Argentina during 2008-2009 and to describe
      the whole genome-based classification of emerging G12P[8] strains detected in our
      country. STUDY DESIGN: Rotavirus positive-samples (n=544) were collected from
      Argentinean children during 2008-2009, as a part of the National Surveillance
      Network for Viral Diarrheas. Specimens were genotyped by reverse transcription
      polymerase chain reaction (RT-PCR) followed by nested-multiplex PCR. Sequencing
      of 11 genome segments was performed in 3 randomly selected G12P[8] strains.
      RESULTS: G9P[8] was the most frequent strain in 2008, but in 2009 G3P[8] and
      G12P[8] were the most frequent strains in different geographical regions of the
      country. The novel emerging G12P[8] strains presented the following combination
      of genes: G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 (i.e. genotype1, Wa-like strains).
      The phylogenetic analysis of the VP7 gene of the G12P[8] strains grouped them
      within lineage III. Previously reported Argentinean G12P[9] strains presented
      genes from genotype 3 (AU-1-like strains) with a VP7 gene from lineage II.
      CONCLUSIONS: The emergence of G12P[8] rotaviruses was due to the introduction of
      a new strain, rather than to a reassortment of the G12P[9] strains previously
      circulating in our country. This study assesses the temporal and geographical
      changes in genotypes prevalence as well as the periodic emergence of unusual G
      genotypes.

PMID- 22410134
TI  - Estimating the probabilities of making a smoking quit attempt in Italy: stall in
      smoking cessation levels, 1986-2009.
AB  - BACKGROUND: No data on annual smoking cessation probability (i.e., the
      probability of successfully quit in a given year) are available for Italy at a
      population level. Mathematical models typically used to estimate smoking
      cessation probabilities do not account for smoking relapse. In this paper, we
      developed a mathematical model to estimate annual quitting probabilities, taking
      into account smoking relapse and time since cessation. METHODS: We developed a
      dynamic model describing the evolution of current, former, and never smokers. We
      estimated probabilities of smoking cessation by fitting the model with observed
      smoking prevalence in Italy, 1986-2009. RESULTS: Annual cessation probabilities
      were higher than 5% only in elderly persons and in women aged < 30 years, while
      in adults aged 30-49 and 50-59 cessations were about 2% and 3-5%, respectively.
      Most of quit probabilities stalled from 1986 to 2009. CONCLUSIONS: Over the last
      20 years, cessation probabilities among Italian smokers, particularly for those
      aged 30-59 years, have been very low and stalled. Quitting in Italy is considered
      as a practicable strategy only by women in the age of pregnancy and by elderly
      persons, when it's likely that symptoms of tobacco-related diseases have already
      appeared. In order to increase cessation probabilities, smoking cessation
      treatment policies (introducing total reimbursement of cessation treatments, with
      a further development of quitlines and smoking cessation services) should be
      empowered and a country-wide mass media campaign targeting smokers aged 30-59
      years and focusing on promotion of quitting should be implemented.

PMID- 22410135
TI  - Varying amounts of different aldehydes present in the cryoprotectants dimethyl
      sulphoxide and 1,2-propanediol.
AB  - Using high-pressure liquid chromatography two cryoprotectant solvents, dimethyl
      sulphoxide (four manufacturers) and 1,2-propanediol (one manufacturer) were
      investigated for aldehyde content. Fractionation of the aldehydes by high
      pressure liquid chromatography identified up to 11 aldehydes and two ketones in
      both cryoprotectant solvents in varying concentrations, which differed between
      manufacturer and container type. Of the 11 aldehydes identified, formaldehyde and
      acetylaldehyde were consistently in the greatest concentrations. As the low
      molecular weight aldehydes identified contain reactive polarised carbonyl groups
      they represent a potential source of intracellular damage when used in oocyte
      cryopreservation.

PMID- 22410136
TI  - Osteopontin upregulation in atherogenesis is associated with cellular oxidative
      stress triggered by the activation of scavenger receptors.
AB  - BACKGROUND: Osteopontin (OPN) is a highly phosphorylated sialoprotein and a
      prominent component of mineralized extracellular matrices of bones and teeth.
      Although the structure of OPN has begun to be elucidated, the role of OPN
      overexpression in tissues distant from the bones and teeth remains poorly
      understood. In the present study, a rabbit model of hypercholesterolemia was
      employed to analyze the relationship between the vascular calcification process
      and OPN overexpression in the neointima of atherosclerotic plaques. METHODS: OPN
      identification in the aorta of experimental animals fed with a high cholesterol
      diet was carried out by immunohistochemical procedures and Western blot analysis
      of tissue homogenates. Transmission electron microscopy was employed to localize
      target-like extracellular structures of atherosclerotic aortas. The human cell
      line T/G HA-VSMC was employed in the establishment of a ROS generation model
      employing the internalization of OxLDL particles. RESULTS: Using
      immunohistochemical and Western blot analysis, OPN overexpression was detected in
      the aortas of rabbits fed a high-cholesterol diet. Results from the
      ultrastructural analysis of the rabbit neointima through transmission electron
      microscopy and from the detection of calcium phosphate precipitates by specific
      histochemical techniques, suggested that OPN may be functionally important as a
      regulator of vascular calcification. OPN was dramatically overexpressed by
      vascular smooth muscle cells in the presence of oxidized and acetylated LDL
      particles bound to scavenger receptors, thereby promoting cytosolic oxidative
      stress. CONCLUSIONS: This study establishes the in vivo role of OPN in the intima
      of the aorta regulating calcium phosphate precipitate deposition in response to
      oxidative stress.

PMID- 22410137
TI  - Latent tuberculosis infection treatment for prison inmates: a randomised
      controlled trial.
AB  - SETTING: A prison in northern Taiwan. OBJECTIVE: To compare safety and the
      completion rate of the 4-month daily rifampicin regimen (4R) vs. the standard 6
      month daily isoniazid regimen (6H) for latent tuberculosis infection (LTBI) in
      prison inmates. DESIGN: This was an open-label  randomised trial among human
      immunodeficiency virus negative male inmates. Inmates without active tuberculosis
      (TB) who tested positive for both the tuberculin skin test and QuantiFERON(r)-TB
      Gold In-Tube were eligible, but those with baseline glutamic pyruvic transaminase
      (GPT) levels >=  120 U/l, bilirubin levels >= 2.4 U/l or a platelet count < 150
      k/mm(3) were excluded. The primary endpoint was any adverse event that resulted
      in discontinuation of LTBI treatment. RESULTS: Participants (n = 373; 14%
      hepatitis B surface antigen positive, 21% anti-hepatitis  C virus [HCV] positive)
      were randomised (stratified by hepatitis B virus, HCV status and 2-year prison
      term) to receive either 4R or 6H under directly observed treatment. The 4R group
      (n = 190) was less likely to experience an adverse event leading to
      discontinuation of treatment (2%  vs. 12%, P < 0.001 for all adverse events; 0%
      vs. 8%, P < 0.001 for hepatotoxicity), and more likely to complete LTBI treatment
      (86% vs. 78%, P = 0.041), compared with the 6H group (n = 183). CONCLUSIONS: 4R
      is safer and has a higher completion rate than  6H as treatment for LTBI among
      male prison inmates.

PMID- 22410138
TI  - Stress and health related quality of life of Nepalese students studying in South
      Korea: a cross sectional study.
AB  - BACKGROUND: In recent years there has been a growing trend among students to
      travel for educational purposes to other countries where there is the possibility
      of experiencing considerable amounts of stress affecting their physical and
      mental functioning. The aims of the current study were to investigate the health
      related quality of life (HRQOL) of Nepalese students studying in South Korea to
      explore the relationship between HRQOL and perceived and acculturative stress,
      and to identify the determinants of HRQOL. METHODS: One hundred and thirty
      students were enrolled in this study. HRQOL was assessed using the Medical
      Outcomes Study Short Forms (SF-12) questionnaire. Perceived stress and
      acculturative stress was measured using the Perceived Stress Scale and
      Acculturative Stress Scale for international students, respectively. Pearson's
      correlation test and multiple regression analysis were performed. RESULTS:
      Perceived stress and acculturative stress were negatively correlated with HRQOL.
      The highest value in the HRQOL was reported for the vitality subscale and the
      lowest value was reported for the role-emotional. In the regression model,
      perceived stress, acculturative stress, relationship with advisor, and marital
      status accounted for a significant (p < .001) portion of the variance (49%) in
      the mental component summary of the HRQOL. CONCLUSIONS: The findings of this
      study indicate that Nepalese students studying in South Korea experience a
      considerable amount of perceived and acculturative stress, which is negatively
      related with their HRQOL. Provision of culture specific counseling and
      orientation programs may benefit the students. The determinants of HRQOL
      identified in this study were perceived stress, acculturative stress,
      relationship with advisor, and marital status.

PMID- 22410139
TI  - Resection of carotid body tumors and the additional choice of intraoperative
      shunt in complicated tumors.
AB  - BACKGROUND: The purpose of this article is to describe an additional choice of
      intraoperative shunt in the surgical repair of complicated carotid body tumors
      (CBTs). METHODS: Between January 2005 and August 2010, 47 CBT resections were
      performed at our division. Thirty-seven patients underwent routine tumor
      resection (78.7%). However, 10 of the tumor resections were complicated because
      of severe adhesions and involvement of the carotid artery. It was difficult to
      excise the tumors using routine methods. Intraoperative shunts were used for
      resection of these 10 complicated tumors (21.3%). RESULTS: All patients underwent
      successful resection of the CBTs. No severe intraoperative or postoperative
      complication was observed in the shunted group. There were two cases with
      hypotension and one case with blood pressure fluctuation in the unshunted group.
      The mean follow-up duration was 35.3 (range, 12-60) months. CONCLUSION: Surgical
      resection is the treatment of choice for CBTs. Shunts are not routinely used in
      the repair and represent just an additional choice for the resection of
      complicated CBTs. In this study, shunts have been shown to maintain cerebral
      circulation, decrease the size of tumor by excluding the vascular supply of the
      external carotid artery, and guide the resection when the tumors were complicated
      and difficult to excise. Shunt insertion was found to be safe and not associated
      with severe cerebrovascular complications.

PMID- 22410140
TI  - Symptomatic fibromuscular dysplasia of the external iliac artery.
AB  - The aim of this article is to report a case of symptomatic fibromuscular
      dysplasia (FMD) involving the external iliac arteries (EIAs). An 88-year-old
      woman was admitted to the vascular service, with a painful right posterior ankle
      ulcer that had progressively worsened during the course of a month. Her medical
      history included diabetes and hypertension. Bilateral lower-extremity pulses were
      absent, and femoral and tibial Doppler waveforms were monophasic. Pelvic and
      bilateral lower-extremity angiograms were obtained, which revealed findings in
      both EIAs consistent with a diagnosis of extrarenal FMD. Percutaneous
      transluminal angioplasty with subsequent stenting of the right EIA was performed,
      using a self-expanding stent. Completion digital subtraction angiography
      demonstrated a widely patent right EIA with brisk flow of contrast across the
      stent. Postprocedural arterial duplex scan showed a biphasic waveform pattern in
      the common femoral artery. FMD can involve the EIA and be associated with
      critical limb ischemia. FMD of the EIA responds well to endovascular management.

PMID- 22410141
TI  - Adoption of endovascular repair of abdominal aortic aneurysm in California:
      lessons for future dissemination of surgical technology.
AB  - BACKGROUND: Knowledge of the pattern of adoption of endovascular approach
      (endovascular aortic repair [EVAR]) to abdominal aortic aneurysm (AAA) could
      direct future dissemination of complex surgical technology. METHODS:
      Retrospective longitudinal analysis of the California Office of Statewide Health
      Planning and Development inpatient database from 2001 to 2008, accompanied by a
      cross-sectional survey of surgeons. The setting was all inpatient hospitals in
      California. Patients were those who underwent repair of AAA. The main outcome
      measure was the endovascular repair of AAA and the training experience of the
      surgeons. RESULTS: Of the 33,277 patients with AAA, 11,755 (35%) underwent
      endovascular repair; 76% were men, mean age was 73 (median, 75) years, 13% of
      aneurysms were ruptured, and 20% were treated at teaching hospitals. The rate of
      EVAR increased from 19% in 2001 to 55% in 2008. On multivariate analysis,
      calendar year, older age, male gender, nonruptured status, teaching hospitals,
      and high-volume hospitals, but not race or insurance status, were identified as
      independent predictors of EVAR. The survey revealed that surgeons with >=15 years
      of experience obtained their training primarily from the manufacturer (58.8%),
      whereas those with <15 years of experience obtained their training primarily
      during residency or fellowship (96.7%). CONCLUSION: Between 2001 and 2008, there
      was a 290% increase in the rate of EVAR for AAA in California. The early adopters
      obtained their training directly or indirectly from the manufacturers. Training
      programs did not begin to offer formal training in this technology until the
      rapid growth was already taking place. This suggests that academic medical
      centers and/or professional organizations should develop plans to play a stronger
      and earlier role in educating physicians about a new technology.

PMID- 22410142
TI  - Long-term results of stenting of the aortic bifurcation.
AB  - BACKGROUND: To evaluate the long-term results in a multicentric continuous series
      of narrowing lesions of the aortic bifurcation treated with a kissing stent.
      METHODS: From January, 1st 1999 to the December, 31st 2001, all of the patients
      (n = 80) presenting with stenosis of the aortic bifurcation (n = 15) and/or the 2
      common iliac arteries (n = 65), treated with a kissing stent, in 8 teaching
      hospitals were collected retrospectively. The risk factors were smoking (91%),
      dyslipidemia (60%), arterial hypertension (42%) and diabetes (27%). In 84% of
      cases, the indication for treatment was claudication. The lesions were stenotic <
      70% (n = 76) and/or thrombotic (n = 18). The associated lesions were external
      iliac stenoses (n = 21), common femoral stenoses (n = 19), femoro-popliteal
      stenoses (n = 42), arteriopathy in the leg (n = 35). Follow-up was clinical
      examination and Doppler US scan. RESULTS: The success rate of the technique was
      89%. There were 4 cases (5.3%) of residual stenosis and 4 cases (5.3%) of
      dissection. The length of the lesions treated in the aorta and the iliac arteries
      was respectively 17.1 +/- 7 and 17.3 +/- 9 mm. The stents were all placed as
      kissing stents, and had a mean diameter and a mean length of 13.75 mm and 56 mm
      in the aorta and 9 mm and 48 mm in the iliac arteries, respectively. At 5 years,
      19 patients had required repeat angioplasty in the treated area, and 13 had
      undergone open surgery. Primary and assisted primary patency at 5 years were
      64.5% and 81.8%, respectively. CONCLUSION: Long-term follow-up of endovascular
      treatment with kissing stents for stenosis of the aortic bifurcation shows that
      this technique gives good results, though it does not justify doing away with
      classical revascularisation surgery, in a population with major cardiovascular
      risk factors.

PMID- 22410143
TI  - Long-term follow-up of endovascular treatment for trans-Atlantic inter-society
      consensus II type B Iliac lesions in patients aged <50 years.
AB  - BACKGROUND: To study the initial and long-term results of endovascular treatment
      in patients aged <50 years with trans-Atlantic inter-society consensus-II type B
      unilateral iliac lesions and chronic limb ischemia. METHODS: From January 2000 to
      February 2010, 60 consecutive endovascular interventions were performed on 23
      women and 37 men aged <=50 years. After successful treatment, all patients were
      followed up at 1, 3, 6, and 12 months after the procedure and every 6 months
      thereafter. RESULTS: Successful percutaneous revascularization of the iliac
      artery was achieved in 56 patients (93.3%). The early vascular-related
      complication rate was 6.7%. The primary patency rates at 1, 3, and 5 years were
      88%, 59%, and 49%, respectively. Cox univariate analysis revealed that an age
      range of 45 to 50 years (hazard ratio [HR]: 0.290; 95% confidence interval [CI]:
      0.152-0.553; P = 0.0001), lower preprocedural ankle-brachial index (HR: 2.438;
      95% CI: 1.04-5.715; P = 0.047), lesion length >5 cm (HR: 0.838; 95% CI: 0.746
      0.943; P = 0.003), and diabetes (HR: 2.005; 95% CI: 1.010-3.980; P = 0.047) had
      significant influence on decreasing primary patency. CONCLUSIONS: Endovascular
      treatment of TASC-II type B iliac lesions in patients aged <50 years is a safe
      procedure with low procedural risk. Primary patency rates at 1, 3, and 5 years
      were 88%, 59%, and 49%, respectively.

PMID- 22410144
TI  - Updated systematic review and meta-analysis of randomized clinical trials
      comparing carotid artery stenting and carotid endarterectomy in the treatment of
      carotid stenosis.
AB  - BACKGROUND: To compare carotid artery stenting (CAS) versus carotid
      endarterectomy (CEA) in the treatment of carotid stenosis, including two recently
      published, large, prospective, randomized trials of these therapies. METHODS: We
      searched electronic databases for prospective, randomized, controlled trials
      involving carotid stenosis patients who underwent CAS or CEA, focusing on studies
      published in 1995 to 2010. Primary outcomes were death, stroke, and myocardial
      infarction. RESULTS: Thirteen trials containing 7,501 patients were analyzed, and
      odds ratios (ORs) were calculated for CAS versus CEA. The risk of stroke or death
      within 30 days was higher after CAS than CEA (OR = 1.57; 95% confidence interval
      [CI] = 1.11-2.22), especially in previously symptomatic patients (OR = 1.89; 95%
      CI = 1.48-2.41). However, the risk of stroke or death within 1 year was
      comparable (OR = 1.12; 95% CI = 0.55-2.30). In a subgroup analysis, the risk of
      death and disabling stroke at 30 days did not differ significantly between CEA
      and CAS (death: OR = 1.43; 95% CI = 0.85-2.40; disabling stroke: OR = 1.28; 95%
      CI = 0.89-1.83), whereas the rate of nondisabling stroke within 30 days was much
      higher in the CAS group (OR = 1.87; 95% CI = 1.40-2.50). The risks of myocardial
      infarction within 30 days and 1 year were significantly less for CAS. CONCLUSION:
      CAS is inferior to CEA with regard to the incidence of stroke or death for
      periprocedural outcomes, especially in symptomatic patients. However, CAS was
      associated with a lower incidence of myocardial infarction. These procedures may
      be considered complementary rather than competing modes of therapy, each of which
      can be optimized with careful patient selection.

PMID- 22410145
TI  - A rare case of visceral arterial stenoses in Williams-Beuren syndrome treated by
      complex revascularization.
AB  - Williams-Beuren syndrome is a rare neurodevelopmental disorder. We present the
      case of a 27-year-old patient with Williams-Beuren syndrome and a juxtarenal
      abdominal aorta coarctation. As arterial hypertension (AHT) was not controlled,
      bilateral renal artery bypasses were performed at the age of 2 years by means of
      a hepatorenal bypass and a splenorenal bypass. Twenty years later, the patient
      presented with abdominal pain, diarrhea, and recurrence of AHT, and severe celiac
      artery and superior mesenteric artery stenoses were discovered. The distal
      arterial complications of this syndrome are uncommon. After 5 years of medical
      treatment, aggravation of the patient's symptoms prompted us to consider possible
      surgical management. The patient was successfully treated using a complex direct
      and indirect procedure that consisted of a bypass between the celiac aorta and
      infrarenal aorta, associated with a celiac artery bypass. Instead of endovascular
      management, this surgical procedure could be considered effective and long
      lasting for treating this rare cause of renal AHT.

PMID- 22410146
TI  - Alteration of the actin cytoskeleton and localisation of the alpha6beta1 and
      alpha3 integrins during regeneration of the rat submandibular gland.
AB  - OBJECTIVES: Actin filaments, which are regulated by signal transduction via
      integrins, play important roles in the regulation of cell differentiation and
      polarity. The aim of this study was to assess alterations in the cytoskeleton and
      the localisation of integrins during regeneration of the rat submandibular gland.
      DESIGN: After obstruction for 7 days, the regenerating glands were collected at
      days 0, 1, 3, 7, 14 after duct release for analysis of regeneration. Alterations
      in the actin filaments were examined using phalloidin, which specifically binds
      to filamentous actin (F-actin), and the distributions of the alpha6beta1 and
      alpha3 integrins were examined immunohistochemically. RESULTS: F-actin was
      strongly localised at the apical region in the intercalated ducts of normal and
      day-14 glands and in duct-like structures during the regenerative process.
      Thereafter, actin accumulated at the basement membrane in mature acinar cells. A
      temporo-spatial correlation was found between the apical distribution of F-actin
      and alpha3 integrin staining. Diffuse alpha6beta1 integrin staining, which
      occurred at a distal site in alpha3 integrin-positive cells, was observed in
      immature cells at day 3. At day 14, alpha6beta1 integrin was detected at the
      basement membrane in terminal differentiated acinar cells. CONCLUSION: These
      findings suggest that duct-like structures have the same properties as
      intercalated ducts, that alterations in alpha3 to alpha6beta1 integrins regulate
      the generation of acinar cells from duct-like structures, and that the
      alpha6beta1 integrin is involved in the differentiation of acinar cells during
      regeneration of the rat submandibular gland.

PMID- 22410147
TI  - Application of eGFP to label human periodontal ligament stem cells in periodontal
      tissue engineering.
AB  - OBJECTIVES: To establish human periodontal ligament stem cells (hPDLSC) with high
      and stable expression of enhanced green fluorescent protein (eGFP) and to obtain
      an ideal vector expression system that suitable for gene therapy in periodontal
      tissue engineering. METHODS: hPDLSCs were transfected with eGFP for 48h via
      different MOI (25, 50, 100, 200 and 400) by lentiviral vector, the transfection
      efficiency was evaluated by fluorescent microscopy and flow cytometry, and
      transfected hPDLSCs proliferation was evaluated by MTT. Pluripotent,
      differentiation capacity and ALP expression status were determined further.
      Osteoblast-associated genes expressions for osteogenesis were evaluated by
      quantitative-PCR. In addition, rat molar periodontal fenestration defect model
      was used for evaluating periodontal tissue engineering. RESULTS: The transfection
      efficiency after 48h were 44.7%, 60.9%, 71.7%, 85.8%, and 86.9% respectively.
      There was no significant effect of transfection (at different MOI levels of 25,
      50, 100, and 200) on the proliferation of hPDLSCs (designated as eGFP-hPDLSCs)
      compared with hPDLSCs (P>0.05). However, proliferation of eGFP hPDLSCs at MOI 400
      became slower (P<0.05). Both eGFP hPDLSCs and hPDLSCs were able to differentiate
      into osteocytes and adipocytes under certain conditioned media. At 7 days,
      expression levels of COL-1, RUNX2 in hPDLSCS were higher than those in eGFP
      hPDLSCs (P<0.05); expression levels of ALP and OPN in eGFP hPDLSCs were similar
      to those in hPDLSCs (P>0.05). Newly regenerated bone formation was observed in
      the defect model used. CONCLUSIONS: Among the transfection conditions, 48h
      transfection at MOI 200 is optimal for labelling hPDLSCs with eGFP in a
      lentiviral vector. There is no change in capability of the eGFP hPDLSCs
      osteogenesis. The lentiviral vector with eGFP is an appropriate expression vector
      system and hPDLSCs are ideal seeding cells for gene therapy in periodontal tissue
      engineering.

PMID- 22410148
TI  - [Our scientific production in the field of spondyloarthritis].
AB  - GRESSER (the Spondyloarthritis Study Group of SER) reunites, since 1999, Spanish
      rheumatologists interested in learning and disseminating knowledge on
      spondyloarthritis, and over the years has maintained an important scientific
      activity based on the development of various research projects (Regisponser and
      follow up cohorts: Early and EA, respondia, the ESPERANZA Program, etc.,) which
      has resulted in interesting scientific publications and high impact
      communications in national and international journals. However, and despite this
      production being very noticeable, Gresser has managed, above all, to draw
      attention to these diseases by Spanish rheumatologists and create an interesting
      field of study that offers new and young professionals, in one way or another,
      access to these intriguing conditions.

PMID- 22410149
TI  - Effect of azithromycin on natural killer cell function.
AB  - Azithromycin (AZM), a macrolide antibiotic for treating mycoplasma infections,
      may exhibit anti-inflammatory activity aside from its antimicrobial effect,
      providing additional therapeutic benefit. Natural killer (NK) cells, a first-line
      innate immune defense against microbial invasions, paradoxically exert a
      detrimental effect in protecting mycoplasma infection. Little was known regarding
      the effect of AZM on NK cells. In the present study, we investigated the ability
      of azithromycin to influence natural killer (NK) cell function with regard to
      activation, apoptosis and cytotoxic function. AZM had little effect on NK
      receptor expression and cytotoxic function of NK-92 cells. However, AZM did show
      a dose-dependent suppression on IL-15-induced CD69 expression of primary NK
      cells. AZM inhibited the cytotoxicity against K562 cells of resting and IL-15
      activated primary NK cells possibly through down-regulation of perforin
      expression, especially on CD16(+)CD56(+) NK subsets. AZM exerted a dose-dependent
      inhibition of IFN-gamma and TNF-alpha production from NK-92 cells, but did not
      affect the cytokine production of IL-15 activated primary NK cells. Taken
      together, AZM down-regulates NK cytotoxicity and cytokine production and may
      provide therapeutic benefits aside from its antimicrobial activity.

PMID- 22410150
TI  - Rescue treatment with tocilizumab for Takayasu arteritis resistant to TNF-alpha
      blockers.
AB  - Anti-TNF-alpha therapy has successfully been used to treat Takayasu arteritis
      (TA) refractory to conventional immunosuppressive treatment. However, some
      patients fail to respond even to TNF-alpha blockers. Interleukin-6 (IL-6) is a
      key player in the pathogenesis of TA. Preliminary data also suggest efficacy of
      the IL-6 receptor inhibitor tocilizumab in patients with large-vessel vasculitis.
      We report a patient with TA refractory to multiple conventional immunosuppressive
      agents and two TNF-alpha blockers successfully treated with monthly tocilizumab
      infusions (8 mg/kg body weight) for 6 consecutive months. Clinical indices of
      disease activity, inflammatory markers, and 18Ffluorodeoxyglucose positron
      emission/computerised tomography findings normalised, while the prednisone dosage
      could be tapered. Serum IL-6 and soluble IL-6 receptor (sIL-6R) levels raised
      during tocilizumab treatment consistent with the mode of action of tocilizumab.
      Tocilizumab holds promise for patients with refractory TA. Larger studies are
      required to confirm our findings.

PMID- 22410151
TI  - Hydrophilic modification of silica-titania mesoporous materials as restricted
      access matrix adsorbents for enrichment of phosphopeptides.
AB  - A new nano-scale restricted-access matrix (RAM) SiO2 (MCM-41) with relatively
      high Ti-content (Ti/Si=0.1), but superior surface area (1129 m2/g), was
      successfully synthesised for the enrichment of phosphopeptides. The TiO2 was
      incorporated into the Si-MCM-41 via a hydrothermal process and the external
      surface was modified with alkyl diol by the successive hydrolysis of gamma
      (glycidyloxypropyl) trimethoxysilane (GPTMS). Scanning electron microscopy,
      transmission electron microscopy, N2 adsorption and Fourier transform infrared
      spectroscopy were used to characterise the alkyl diol-Ti-MCM-41. The appropriate
      pore diameter (2 nm) coupled to the marshy weeds-like hydrophilic external
      surface result in an efficient size-exclusion effect for the adsorption of
      standard cytochrome c with a molecular weight (MW) of ca. 12.4 kDa. At the same
      time, the strong affinity interaction between the incorporated titanium in the
      framework and the phosphoryl groups of phosphopeptides demonstrated a selective
      extract of phosphopeptides from the tryptic digestion. The detection sensitivity
      for phosphopeptides, determined by matrix-assisted laser desorption/ionisation
      time-of-flight mass spectrometry (MALDI-TOF MS) was as low as 5 fmol for standard
      tryptic digest of beta-casein. Therefore, this alkyl diol-Ti-MCM-41 mesoporous
      material can be used as a potential adsorbent for applications in MS-based
      phosphoproteomics.

PMID- 22410152
TI  - Integration parameters and their effects on quantitative results with two-step
      peak summation quantitation in comprehensive two-dimensional gas chromatography.
AB  - Quantification of comprehensive two-dimensional gas chromatographic (GC*GC) data
      in a commercial software package is examined. ChromaTOF((r)) (Leco Instruments)
      includes a smoothing step prior to data integration. Improper choice of
      integration parameters can introduce errors in excess of +/-10% and as high as
      60% in the total peak area. Herein we demonstrate the critical nature of the
      smoothing parameters in this software, particularly the expected peak width in
      the second dimension ((2)w) which should be verified as part of a QA/QC protocol.

PMID- 22410153
TI  - Low-density solvent based ultrasound-assisted emulsification microextraction and
      on-column derivatization combined with gas chromatography-mass spectrometry for
      the determination of carbamate pesticides in environmental water samples.
AB  - A fast and efficient method for the determination of trace level of carbamate
      pesticides using a lower-density-than-water solvent for ultrasound-assisted
      emulsification microextraction coupled to on-column derivatization and analysis
      by GC-MS has been developed and studied. In this approach, a soft plastic Pasteur
      pipette was employed as a convenient extraction device. Fifty microliters of
      extraction solvent, of lower density than water, was injected into the sample
      solution held in the pipette. The latter was immediately immersed in an
      ultrasound water bath to form an emulsion. After 2 min extraction, the emulsion
      was fractionated into two layers by centrifugation. The upper layer (organic
      extract) could be collected conveniently by squeezing the bulb of the pipette,
      now held upside down, to move it into the narrow stem of the device, facilitating
      its retrieval for analysis. The extract was then combined with
      trimethylphenylammonium hydroxide and directly injected into a gas chromatography
      mass spectrometry (GC-MS) system for on-column derivatization and analysis. The
      on-column derivatization provided an added convenience (since a separate step was
      not necessary). Parameters affecting the derivatization and extraction were
      investigated. Under the most favorable conditions, the method demonstrated high
      extraction efficiency with low limits of detection of between 0.01 and 0.1 MUg/L,
      good linearity in the range of 0.05-50 MUg/L, to 0.5-100 MUg/L, and good
      repeatability (RSD below 9.2%, n=5). The proposed method was evaluated by
      determining carbamate pesticides in river water samples.

PMID- 22410154
TI  - High sensitivity measurements of active oxysterols with automated
      filtration/filter backflush-solid phase extraction-liquid chromatography-mass
      spectrometry.
AB  - Oxysterols are important in numerous biological processes, including cell
      signaling. Here we present an automated filtration/filter backflush-solid phase
      extraction-liquid chromatography-tandem mass spectrometry (AFFL-SPE-LC-MS/MS)
      method for determining 24-hydroxysterol and the isomers 25-hydroxycholesterol and
      22S-hydroxycholesterol that enables simplified sample preparation, high
      sensitivity (~25 pg/mL cell lysis sample) and low sample variability. Only one
      sample transfer step was required for the entire process of cell lysis,
      derivatization and determination of selected oxysterols. During the procedure,
      autoxidation of cholesterol, a potential/common problem using standard analytical
      methods, was found to be negligible. The reversed phase AFFL-SPE-LC-MS/MS method
      utilizing a 1mm inner diameter column was validated, and used to determine levels
      of the oxysterol analytes in mouse fibroblast cell lines SSh-LII and NIH-3T3, and
      human cancer cell lines, BxPC3, HCT-15 and HCT-116. In BxPC3 cells, the AFFL-SPE
      LC-MS/MS method was used to detect significant differences in 24S-OHC levels
      between vimentin+ and vimentin- heterogenous sub-populations. The methodology
      also allowed monitoring of significant alterations in 24S-OHC levels upon
      delivery of the Hedgehog (Hh) antagonist MS-0022 in HCT-116 colorectal carcinoma
      cell lines.

PMID- 22410155
TI  - Multi-dimensional gas chromatography with a planar microfluidic device for the
      characterization of volatile oxygenated organic compounds.
AB  - Oxygenated compounds like methanol, ethanol, 1-propanol, 2-propanol, 1-butanol,
      acetaldehyde, crotonaldehyde, ethylene oxide, tetrahydrofuran, 1,4-dioxane, 1,3
      dioxolane, and 2-chloromethyl-1,3-dioxolane are commonly encountered in
      industrial manufacturing processes. Despite the availability of a variety of
      column stationary phases for chromatographic separation, it is difficult to
      separate these solutes from their respective matrices using single dimension gas
      chromatography. Implemented with a planar microfluidic device, conventional two
      dimensional gas chromatography and the employment of chromatographic columns
      using dissimilar separation mechanisms like that of a selective wall-coated open
      tubular column and an ionic sorbent column have been successfully applied to
      resolve twelve industrially significant volatile oxygenated compounds in both gas
      and aqueous matrices. A Large Volume Gas Injection System (LVGIS) was also
      employed for sample introduction to enhance system automation and precision. By
      successfully integrating these concepts, in addition to having the capability to
      separate all twelve components in one single analysis, features associated with
      multi-dimensional gas chromatography like dual retention time capability, and the
      ability to quarantine undesired chromatographic contaminants or matrix components
      in the first dimension column to enhance overall system cleanliness were
      realized. With this technique, a complete separation for all the compounds
      mentioned can be carried out in less than 15 min. The compounds cited can be
      analyzed over a range of 250 ppm (v/v) to 100 ppm (v/v) with a relative standard
      deviation of less than 5% (n=20) with high degree of reliability.

PMID- 22410156
TI  - Liquid chromatography-flame ionisation detection using a nebuliser/spray chamber
      interface. Part 1. Design and testing.
AB  - A nebuliser and spray chamber have been used to link a flow injection analyser to
      a flame ionisation detector, with the potential for the combination to be used as
      a universal detector for liquid chromatography. The hydrogen and air flows were
      adjusted to achieve a stable system. The detector responded to both volatile and
      involatile analytes and to compounds with and without chromophores, including
      alkanes, alkanols, aromatic amides and acids, phenols, amino-acids and
      carbohydrates and gave a linear response for many analytes. However, for
      involatile polar analytes it was necessary to add traces of acid or salt to the
      carrier stream to obtain a linear response.

PMID- 22410157
TI  - Synthesis of sulfo/vinyl biphasic silica hybrid monolithic capillary column and
      its application to on-column preconcentration for capillary
      electrochromatography.
AB  - A novel method to synthesize sulfo/vinyl biphasic silica hybrid monolithic column
      in one step was developed for on-column preconcentration. In this method, sulfo
      based segment is located at the inlet of capillary column, which acts as
      preconcentration column. It is synthesized by polymerization of 3-sulfopropyl
      methacrylate potassium salt (SPMA) and vinyltrimethoxysilane (VTMS) with
      tetramethoxysilane (TOMS). Close to the preconcentration column, a vinyl
      functionalized segment is formed and serves as separation column. It is
      synthesized by polymerization of only VTMS with TOMS. Vinyl groups on vinyl
      functionalized segment are modified with ligand containing sulfhydryl group, such
      as octadecanethiol (C(18)-SH for short), 6-mercapto-1-hexanol (HO-C(6)-SH for
      short), via thiol-ene click reaction. The interface between the two segments is
      seamless and without any dead volume. The applicability of this system is
      demonstrated by successful separation of closely related amines including p
      phenylenediamine, aniline, p-toluidine, N-methyl aniline, N,N'-dimethylaniline,
      and diphenylamine. Good separation and enrichment are obtained. The proposed
      system is also successfully applied to complex biological samples, such as
      peptide, diluted BSA hydrolysate, and the results indicate that the system has a
      capability for preconcentration of low abundance peptides.

PMID- 22410158
TI  - Partial filling affinity capillary electrophoresis using large-volume sample
      stacking with an electroosmotic flow pump for sensitive profiling of glycoprotein
      derived oligosaccharides.
AB  - An online preconcentration technique, large-volume sample stacking with an
      electroosmotic flow pump (LVSEP) was combined with partial filling affinity
      capillary electrophoresis (PFACE) to realize highly sensitive analysis of the
      interaction of glycoprotein-derived oligosaccharides with some plant lectins.
      Oligosaccharides derivatized with 8-aminopyrene-1,3,6-trisulfonic acid (APTS)
      were delivered to an entire neutrally-coated capillary and then lectin solution
      was hydrodynamically introduced from the outlet of the capillary as a short plug.
      A negative voltage was then applied after immersion of both ends of the capillary
      in 100 mM Tris-acetate buffer, pH 7.0 containing 0.5% hydroxypropylcellulose as
      electrophoresis buffers. A low concentration of electrolytes in the sample
      solution causes a significant flow by electroendosmosis from anode to cathode and
      the APTS-labeled oligosaccharides move quickly towards the anode and concentrate
      in the lectin phase. Finally, electroosmotic flow becomes negligible when the
      capillary is filled with the background electrolyte delivered from the anodic
      reservoir and APTS-labeled saccharides pass through the lectin plug and are
      detected at the anodic end. If the APTS-labeled oligosaccharides are recognized
      by the lectin, the migration profiles should be altered. The sensitivity was
      enhanced by a factor of ca. 900 compared to typical hydrodynamic injection (3.45
      kPa, 10s). By this method, increased residence time of APTS-saccharides in the
      lectin plug indicates highly efficient interaction with lectins, which differs
      completely from the results obtained by ordinary lectin PFACE. The run-to-run
      repeatability (n=18) of the migration time and peak area was high, with relative
      standard deviations of less than 0.7% and 6.1%, respectively.

PMID- 22410159
TI  - Sleep measurement and monitoring in children with Down syndrome: a review of the
      literature, 1960-2010.
AB  - Children with Down syndrome (DS) are at risk for sleep disturbances due to the
      anatomical features of the syndrome. Over the past 50 years research studies have
      measured sleep in children with DS to characterize sleep architecture and its
      relation to developmental delay. In the 1980s sleep disordered breathing (SDB)
      was recognized as a major cause of sleep disturbance in DS. The aim of this
      comprehensive review is to synthesize studies and present the historical context
      of evolving technologies, methodologies, and knowledge about SDB and DS. Future
      research opportunities and practice implications are discussed.

PMID- 22410160
TI  - Difference in symptom severity between early and late grass pollen season in
      patients with seasonal allergic rhinitis.
AB  - BACKGROUND: For the development of forecasts for seasonal allergic rhinitis
      symptoms, it is essential to understand the relationship between grass pollen
      concentrations and the symptoms of grass pollen allergic patients. OBJECTIVE: The
      aim of this study was to delineate this relationship between seasonal allergic
      rhinitis symptoms and grass pollen concentrations in the Netherlands. METHODS:
      Grass pollen allergic patients (n = 80 [2007] - 84 [2008]) were enrolled into the
      study. They were asked to enter their seasonal allergic rhinitis symptoms (runny
      nose, sneezing, blocked nose, post nasal drip, and eye symptoms) daily on a scale
      from 0 to 3 to the study centre either by short message service (SMS) or by
      internet from May-July 2007 and April-July 2008. Daily pollen counts were used to
      define the early and the late grass pollen season as the period 'before and
      during' respectively 'after' the first grass pollen peak (more than 150
      pollen/m3). RESULTS: At similar grass pollen concentrations, the daily mean of
      the individual maximum symptom scores reported in the early season were higher as
      compared to that reported in the late season [differences of -0.41 (2007) and 
      0.30 (2008)]. This difference could not be explained by medication use by the
      patients nor by co-sensitization to birch. CONCLUSIONS: We conclude that seasonal
      allergic rhinitis symptoms at similar grass pollen concentrations are more severe
      in the early flowering season as compared to those in the late flowering season.
      This finding is not only relevant for development of forecasts for seasonal
      allergic rhinitis symptoms but also for understanding symptom development and
      planning and analysis of clinical studies.

PMID- 22410161
TI  - Reducing mother-to-child transmission of HIV: findings from an early infant
      diagnosis program in south-south region of Nigeria.
AB  - BACKGROUND: Early diagnosis of HIV in infants provides a critical opportunity to
      strengthen follow-up of HIV-exposed children and assure early access to
      antiretroviral (ARV) treatment for infected children. This study describes
      findings from an Early Infant Diagnosis (EID) program and the effectiveness of a
      prevention of mother-to-child transmission (PMTCT) intervention in six health
      facilities in Cross-River and Akwa-Ibom states, south-south Nigeria. METHODS:
      This was a retrospective study. Records of 702 perinatally exposed babies aged
      six weeks to 18 months who had a DNA PCR test between November 2007 and July 2009
      were reviewed. Details of the ARV regimen received to prevent mother-to-child
      transmission (MTCT), breastfeeding choices, HIV test results, turn around time
      (TAT) for results and post test ART enrolment status of the babies were analysed.
      RESULTS: Two-thirds of mother-baby pairs received ARVs and 560 (80%) babies had
      ever been breastfed. Transmission rates for mother-baby pairs who received ARVs
      for PMTCT was 4.8% (CI 1.3, 8.3) at zero to six weeks of age compared to 19.5%
      (CI 3.0, 35.5) when neither baby nor mother received an intervention. Regardless
      of intervention, the transmission rates for babies aged six weeks to six months
      who had mixed feeding was 25.6% (CI 29.5, 47.1) whereas the transmission rates
      for those who were exclusively breastfed was 11.8% (CI 5.4, 18.1). Vertical
      transmission of HIV was eight times (AOR 7.8, CI: 4.52-13.19) more likely in the
      sub-group of mother-baby pairs who did not receive ARVS compared with mother-baby
      pairs that did receive ARVs. The median TAT for test results was 47 days (IQR: 35
      58). A follow-up of 125 HIV positive babies found that 31 (25%) were enrolled
      into a paediatric ART program, nine (7%) were known to have died before the
      return of their DNA PCR results, and 85 (67%) could not be traced and were
      presumed to be lost-to-follow-up. CONCLUSION: Reduction of MTCT of HIV is
      possible with effective PMTCT interventions, including improved access to ARVs
      for PMTCT and appropriate infant feeding practices. Loss to follow up of HIV
      exposed infants is a challenge and requires strategies to enhance retention.

PMID- 22410163
TI  - Constructing a strategy map for banking institutions with key performance
      indicators of the balanced scorecard.
AB  - This study presents a structural evaluation methodology to link key performance
      indicators (KPIs) into a strategy map of the balanced scorecard (BSC) for banking
      institutions. Corresponding with the four BSC perspectives (finance, customer,
      internal business process, and learning and growth), the most important
      evaluation indicators of banking performance are synthesized from the relevant
      literature and screened by a committee of experts. The Decision Making Trial and
      Evaluation Laboratory (DEMATEL) method, a multiple criteria analysis tool, is
      then employed to determine the causal relationships between the KPIs, to identify
      the critical central and influential factors, and to establish a visualized
      strategy map with logical links to improve banking performance. An empirical
      application is provided as an example. According to the expert evaluations, the
      three most essential KPIs for banking performance are customer satisfaction,
      sales performance, and customer retention rate. The DEMATEL results demonstrate a
      clear road map to assist management in prioritizing the performance indicators
      and in focusing attention on the strategy-related activities of the crucial
      indicators. According to the constructed strategy map, management could better
      invest limited resources in the areas that need improvement most. Although these
      strategy maps of the BSC are not universal, the research results show that the
      presented approach is an objective and feasible way to construct strategy maps
      more justifiably. The proposed framework can be applicable to institutions in
      other industries as well.

PMID- 22410162
TI  - In vivo neuronal firing patterns during human epileptiform discharges replicated
      by electrical stimulation.
AB  - OBJECTIVE: To describe neuronal firing patterns observed during human spontaneous
      interictal epileptiform discharges (IEDs) and responses to single pulse
      electrical stimulation (SPES). METHODS: Activity of single neurons was recorded
      during IEDs and after SPES in 11 consecutive patients assessed with depth EEG
      electrodes and attached microelectrodes. RESULTS: A total of 66 neurons were
      recorded during IEDs and 151 during SPES. We have found essentially similar
      patterns of neuronal firing during IEDs and after SPES, namely: (a) a burst of
      high frequency firing lasting less than 100 ms (in 39% and 25% of local neurons,
      respectively for IED and SPES); (b) a period of suppression in firing lasting
      around 100-1300 ms (in 19% and 14%, respectively); (c) a burst followed by
      suppression (in 10% and 12%, respectively); (d) no-change (in 32% and 50%,
      respectively). CONCLUSIONS: The similarities in neuronal firing patterns
      associated with IEDs and SPES suggest that, although both phenomena are initiated
      differently, they result in the activation of a common cortical mechanism,
      probably initiated by brief synchronised burst firing in some cells followed by
      long inhibition. SIGNIFICANCE: The findings provide direct in vivo human evidence
      to further comprehend the pathophysiology of human focal epilepsy.

PMID- 22410165
TI  - Non-formal educator use of evaluation results.
AB  - Increasing demands for accountability in educational programming have resulted in
      increasing calls for program evaluation in educational organizations. Many
      organizations include conducting program evaluations as part of the job
      responsibilities of program staff. Cooperative Extension is a complex
      organization offering non-formal educational programs through land grant
      universities. Many Extension services require non-formal educational program
      evaluations be conducted by field-based Extension educators. Evaluation research
      has focused primarily on the efforts of professional, external evaluators. The
      work of program staff with many responsibilities including program evaluation has
      received little attention. This study examined how field based Extension
      educators (i.e. program staff) in four Extension services use the results of
      evaluations of programs that they have conducted themselves. Four types of
      evaluation use are measured and explored; instrumental use, conceptual use,
      persuasive use and process use. Results indicate that there are few programmatic
      changes as a result of evaluation findings among the non-formal educators
      surveyed in this study. Extension educators tend to use evaluation results to
      persuade others about the value of their programs and learn from the evaluation
      process. Evaluation use is driven by accountability measures with very little
      program improvement use as measured in this study. Practical implications include
      delineating accountability and program improvement tasks within complex
      organizations in order to align evaluation efforts and to improve the results of
      both. There is some evidence that evaluation capacity building efforts may be
      increasing instrumental use by educators evaluating their own programs.

PMID- 22410164
TI  - Exposure to school and community based prevention programs and reductions in
      cigarette smoking among adolescents in the United States, 2000-08.
AB  - Smoking remains prevalent among US youth despite decades of antismoking efforts.
      Effects from exposure to prevention programs at national level may provide
      informative and compelling data supporting better planning and strategy for
      tobacco control. A national representative sample of youth 12-17 years of age
      from the National Survey on Drug Use and Health was analyzed. A 3-stage model was
      devised to estimate smoking behavior transitions using cross-sectional data and
      the Probabilistic Discrete Event System method. Cigarette smoking measures
      (prevalence rates and odds ratios) were compared between exposed and non-exposed
      youth. More than 95% of the sample was exposed to prevention programs. Exposure
      was negatively associated with lifetime smoking and past 30-day smoking with a
      dose-response relation. Reduction in smoking was related to increased quitting in
      2000-02, to increased quitting and declined initiation in 2003-05, and to
      initiation, quitting and relapse in 2005-08. Findings of this analysis suggest
      that intervention programs in the United States can reduce cigarette smoking
      among youth. Quitting smoking was most responsive to program exposure and relapse
      was most sensitive to funding cuts since 2003. Health policy and decision makers
      should consider these factors in planning and revising tobacco control
      strategies.

PMID- 22410166
TI  - Evaluation of the mandatory construction induction training program in Western
      Australia: unanticipated consequences.
AB  - Since January 1, 2007, Government legislation in Western Australia required all
      workers in construction to complete mandatory safety awareness training before
      they began work on site. During the implementation of this new legislation there
      was considerable resistance from the construction sector due to the mandatory
      nature of the training. The construction industry viewed this as an unnecessary
      impost as they considered that there was already sufficient safety training
      delivered through individual company and site inductions. In 2010, we evaluated
      the new Construction Induction Training (CIT) in the commercial construction
      sector in Western Australia to find that since 2007 there has been an
      unanticipated change in support for the mandatory training. The 2010 study shows
      a shift in the values of the safety culture for the commercial sector of the
      construction industry. In 2010, the industry not only supports the mandatory CIT,
      but is very vocal in its request to re-institute the refresher courses that were
      withdrawn in 2009. Indeed, 79% of respondents claimed there were measurable
      benefits to their business having their employees complete the CIT, while 96%
      claimed the CIT assisted in reducing accidents/incidents on their worksites. This
      2010 study indicates that in this case, mandatory training has had a positive
      effect on safety culture change and gradually reduced work-related injury in the
      industry since 2007 to the present. The paper uses data from two studies
      conducted in 2006 and 2010 to highlight the unanticipated change in perception of
      the value of mandatory safety training in the WA construction industry to one
      which is positive and supportive.

PMID- 22410167
TI  - Pragmatic fluid optimization in high-risk surgery patients: when pragmatism
      dilutes the benefits.
AB  - There is increasing evidence that hemodynamic optimization by fluid loading,
      particularly when performed in the early phase of surgery, is beneficial in high
      risk surgery patients: it leads to a reduction in postoperative complications and
      even to improved long-term outcome. However, it is also true that goal- directed
      strategies of fluid optimization focusing on cardiac output optimization have not
      been applied in the clinical routine of many institutions. Reasons are manifold:
      disbelief in the level of evidence and on the accuracy and practicability of the
      required monitoring systems, and economics. The FOCCUS trial examined
      perioperative fluid optimization with a very basic approach: a standardized
      volume load with 25 ml/kg crystalloids over 6 hours immediately prior to
      scheduled surgery in high-risk patients. The hypothesis was that this
      intervention would lead to a compensation of preoperative fluid deficit caused by
      overnight fasting, and would result in improved perioperative fluid homeostasis
      with less postoperative complications and earlier hospital discharge. However,
      the primary study endpoints did not improve significantly. This observation
      points towards the facts that: firstly, the differentiation between interstitial
      fluid deficit caused by fasting and intravascular volume loss due to acute blood
      loss must be recognized in treatment strategies; secondly, the type of fluid
      replacement may play an important role; and thirdly, protocolized treatment
      strategies should also always be tailored to suit the patients' individual needs
      in every individual clinical situation.

PMID- 22410168
TI  - Helping women but hurting ourselves? Neck and upper back musculoskeletal symptoms
      in a cohort of Australian Midwives.
AB  - OBJECTIVE: To determine the prevalence of neck and upper back musculoskeletal
      symptoms in a group of Australian midwives and explore individual characteristics
      and workplace exposures associated with these symptoms. DESIGN: cross-sectional,
      using data from the Nurses and Midwives e-Cohort Study, a longitudinal,
      electronic survey of midwives and nurses in Australia, New Zealand and the United
      Kingdom. SETTING: data were collected via an online survey in 2006-2008.
      PARTICIPANTS: qualified Australian midwives aged 23-70 years. MEASUREMENTS AND
      FINDINGS: We undertook descriptive analysis of the sample, calculated prevalence
      and examined associations between individual and workplace variables and neck and
      upper back musculoskeletal symptoms. Variables achieving p<0.1 in bivariate
      analysis were entered simultaneously into logistic regression models. Overall
      prevalence rates were 48.8% for neck and 28.2% for upper back musculoskeletal
      symptoms; work-related prevalence was 40.8% (neck) and 24.5% (upper back),
      comparable to reported rates among nurses and physicians. Presence of symptoms in
      the adjacent area was associated with greater than a fourfold increased risk for
      neck and upper back symptoms. Participants with care responsibility for an adult
      dependent were 36% more likely to report neck symptoms. Current shift work and
      total physical activity were associated with decreased likelihood of neck and
      upper back symptoms, respectively. Psychological job demands were only weakly
      associated with upper back symptoms, possibly because the survey tool could not
      capture a sufficiently broad range of psychosocial exposures to present a
      complete picture. A striking finding was that work in awkward postures conferred
      an increased risk of 35% for neck and nearly 50% for upper back symptoms. KEY
      CONCLUSIONS: neck and upper back musculoskeletal symptoms were prevalent in this
      sample. Both individual and workplace factors were significantly associated with
      neck and/or upper back symptoms. Psychological job demands and work in awkward
      postures are potentially modifiable exposures that deserve further examination.
      IMPLICATIONS FOR PRACTICE: midwives who are or may become carers for adult
      dependents should be aware of a possible increased risk for neck symptoms. It may
      be prudent for midwives and those who employ/supervise them to monitor and, where
      possible, jointly develop strategies to mitigate psychological job demands. The
      potential hazard posed by work in awkward postures warrants consideration of how
      midwives may minimize time spent working in these postures.

PMID- 22410169
TI  - Seeing and holding a stillborn baby: mothers' feelings in relation to how their
      babies were presented to them after birth--findings from an online questionnaire.
AB  - OBJECTIVE: to determine if the way caregivers offer opportunities to see and hold
      a stillborn baby impacts a mother's feelings about the experience of seeing and
      holding her newborn. DESIGN AND SETTING: a web questionnaire hosted by the
      Swedish National Infant Foundation from March 2008 to April 2010. PARTICIPANTS:
      840 eligible participants who had experienced a stillbirth after the 22nd
      gestational week from 1955 to 2010 and completed an online questionnaire about
      their experiences. METHODS: descriptive and inferential statistics. FINDINGS:
      when mothers were presented the baby as a normal part of birth without being
      asked if they wanted to see, they more often reported that the experience was
      comfortable compared to mothers who were asked if they wanted to see the baby 86%
      vs. 76% (p=<0.01). The incitation of fear in mothers was 70% vs. 80% (p=0.02) in
      favour of mothers who were not asked. Furthermore the mothers who were not asked
      more often stated that it felt natural and good when compared to those who said
      staff asked if the mother wanted to see, 73% vs. 61% (p=0.07) and (78%) vs. (69%)
      p=0.19, respectively. A trend was seen toward more mothers feeling natural, good,
      comfortable, and less frightened if the provider engaged in 'assumptive bonding',
      that is the baby is simply and naturally presented to the mother without asking
      her to choose. KEY CONCLUSIONS: mothers of stillborn babies felt more natural,
      good, comfortable and less frightened if the staff supported assumptive bonding
      by simply offering the baby to the mother. IMPLICATIONS FOR PRACTICE: care
      providers should approach caring for grieving mothers with tenderness and
      humility, assuming that they will wish to see and hold their stillborn baby.

PMID- 22410170
TI  - Comparison of antibodies and carbohydrates to target vaccines to human dendritic
      cells via DC-SIGN.
AB  - Vaccine efficacy is improved upon specific delivery to professional antigen (Ag)
      presenting cells, such as dendritic cells (DCs). Antigenicity and adjuvanticity
      of vaccine components can be enhanced by encapsulation within nanoparticle (NP)
      vaccine carriers that are targeted to the human DC-specific C-type lectin
      receptor DC-SIGN. Here we used two strategies to target vaccines components to DC
      SIGN: 1) carbohydrates as natural receptor ligands and 2) receptor-specific
      antibodies (Abs). To determine the optimal targeting strategy, we coated NP
      vaccines harboring MHC class I or II-restricted Ags and the TLR ligands (TLRLs)
      poly I:C and resiquimod with either the DC-SIGN ligands Lewis-X (Le(x)),
      mannosylated lipoarabinomannan (ManLAM), glycosylated HIV protein gp120, or three
      distinct DC-SIGN Abs. Although, because of their lower MW, surface coating of NP
      vaccines with carbohydrates resulted in a higher number of surface molecules per
      NP than coating with Abs, NP vaccines carrying Abs were more effectively bound
      and internalized by human DCs than carriers harboring Le(x), ManLAM or gp120.
      Furthermore, NP vaccines harboring TLRLs triggered significant induction of DC
      maturation markers when compared to those without TLRLs, irrespective of the
      targeting moiety. Ab- and gp120-mediated targeting induced equally high levels of
      proinflammatory cytokines and increased presentation of the MHC class I
      restricted epitope. By contrast, presentation of the MHC class II-restricted
      epitope was more efficient upon Ab-mediated targeting than when using gp120,
      Le(x) or ManLAM. From these findings we conclude that receptor-specific Abs are
      more effective than carbohydrates for DC-targeted vaccination strategies.

PMID- 22410171
TI  - Laminin active peptide/agarose matrices as multifunctional biomaterials for
      tissue engineering.
AB  - Cell adhesive peptides derived from extracellular matrix components are potential
      candidates to afford bio-adhesiveness to cell culture scaffolds for tissue
      engineering. Previously, we covalently conjugated bioactive laminin peptides to
      polysaccharides, such as chitosan and alginate, and demonstrated their advantages
      as biomaterials. Here, we prepared functional polysaccharide matrices by mixing
      laminin active peptides and agarose gel. Several laminin peptide/agarose matrices
      showed cell attachment activity. In particular, peptide AG73
      (RKRLQVQLSIRT)/agarose matrices promoted strong cell attachment and the cell
      behavior depended on the stiffness of agarose matrices. Fibroblasts formed
      spheroid structures on the soft AG73/agarose matrices while the cells formed a
      monolayer with elongated morphologies on the stiff matrices. On the stiff
      AG73/agarose matrices, neuronal cells extended neuritic processes and endothelial
      cells formed capillary-like networks. In addition, salivary gland cells formed
      acini-like structures on the soft matrices. These results suggest that the
      peptide/agarose matrices are useful for both two- and three-dimensional cell
      culture systems as a multifunctional biomaterial for tissue engineering.

PMID- 22410172
TI  - Two novel EGFP insertion alleles reveal unique aspects of Pax2 function in
      embryonic and adult kidneys.
AB  - The Pax2 gene encodes a DNA binding protein with multiple functions in the
      developing intermediate mesoderm and urogenital tract. Loss of Pax2 in mice
      results in the complete absence of kidneys, ureters, and sex specific epithelial
      structures derived from the intermediate mesoderm in both males and females. In
      this report, we describe two new alleles of Pax2 created by inserting the
      enhanced green fluorescent protein coding region into the 5' untranslated leader
      sequence. One allele is a hypomorph that generates less protein and exhibits
      structural defects in kidneys and ureters upon homozygosity. A second allele is a
      true null that can be used to image Pax2 expressing cells in a mutant background.
      Organ culture and embryo analyses point to a loss of epithelial cell polarity and
      increased mobility in cells that have deleted Pax2 function. These experiments
      provide new insight into the role of Pax2 protein levels in determining correct
      renal architecture and cell fate. These new Pax2 alleles are valuable genetic
      reagents for in vivo studies of urogenital development.

PMID- 22410173
TI  - MRI findings in patients with central neurocytomas with special reference to
      differential diagnosis from other ventricular tumours near the foramen of Monro.
AB  - We retrospectively evaluated 12 patients with histologically verified central
      neurocytoma (CN) to identify the MRI characteristics associated with this tumour.
      All tumours had heterogeneous signal intensity in their solid components and
      seven had a "soap bubble" or spongy appearance. Spicules were identified at the
      tumour periphery interfacing with the lateral ventricular walls. These spicules
      were formed by walls of multiple cysts of medium size. Undulation of the lateral
      ventricular wall attached to the tumour capsule was seen in nine patients. These
      spicules and undulations resulted in a "scalloping" appearance. In a diagnostic
      experiment to test the differential diagnosis of CN from other neoplasms near the
      foramen of Monro, the identification of scalloping made a greater contribution to
      the specificity and accuracy of the diagnosis than the soap bubble appearance.
      Thus, recognition of multiple cystic interfaces between the solid part of the
      tumour and the lateral ventricular wall on MRI may contribute to a correct
      preoperative diagnosis of CN.

PMID- 22410174
TI  - Malignancies associated with systemic sclerosis.
AB  - The outcome of systemic sclerosis (SSc) has become more favorable during the past
      years. Respiratory failure or renal crisis became less frequent, therefore more
      attention should be paid to long-term comorbidities, such as malignancies
      secondary to scleroderma. The incidence of malignant lymphoproliferative
      diseases, as well as that of solid tumors are higher in a number of rheumatic
      diseases including SSc. Some cytotoxic agents, primarily cyclophosphamide used in
      the treatment of SSc, as well as exposure to chemicals or smoking may further
      increase cancer risk. We also present malignancies in 218 scleroderma patients
      undergoing follow-up in our department were assessed for secondary malignancies.
      Although the number of SSc patients with tumor is relatively small, we compared
      our cohort to the Health for All Hungarian database and calculated standard
      incidence ratios (SIR). We identified 11 cases of malignancy in 10 SSc patients
      (4.6%). One patient had two types of tumor: breast cancer before the onset of SSc
      and later malignant lymphoma. Half of SSc patients with cancer belonged to the
      diffuse cutaneous (dcSSc) subtype. The mean age at onset of SSc was 54.6 years,
      while that at the diagnosis of malignancy was 61.5 years. The mean disease
      duration of scleroderma at the time of cancer diagnosis was 6.6 years. Five
      patients died, 4 due to the underlying malignancy. Among the five surviving
      patients, the mean survival time was 4.9 years. Altogether 3 patients had non
      Hodgkin's lymphoma, 2 had bronchial cancer, 2 had breast cancer, one had
      leiomyosarcoma of the leg, one had esophageal cancer, one had cervix cancer and
      one had skin cancer. In comparison to the Health for All database, the overall
      SIR of all malignancies in SSc was 1.07 (CI: 0.82-1.38) varying between 5.8 and
      52.4 in different tumor types. Only one cancer patient received cyclophosphamide
      therapy. In conclusion, secondary tumors including lung, skin and breast cancer,
      as well as lymphomas are more common in SSc than in the general population. The
      adequate treatment and follow-up of scleroderma patients may help us to lower the
      risk of malignancies secondary to SSc.

PMID- 22410176
TI  - A regulatory approach to assess the potency of substances toxic to the
      reproduction.
AB  - In order to develop a method for setting specific concentration limits (SCLs) for
      substances toxic to the reproduction within the European classification and
      labelling system, this study investigated possible parameters for reproductive
      toxicity potency and the quantitative distribution of those parameters. For that
      purpose, two databases were created comprising substances classified in the
      European Union for developmental toxicity or for effects on sexual function and
      fertility. For these substances six parameters including NOAEL, LOAEL and ED(10)
      were determined for effects on reproduction based on existing data summaries. The
      potency was defined independent of the type of reproductive effect as generally
      severe effects on reproduction warranting classification were already observed at
      the lowest dose showing reproductive effects. The reproductive toxicity potency
      range of substances in the databases was a factor of approximately one million.
      This shows that SCL setting is needed to adjust the classification of mixtures.
      The average potency distribution of substances classified according to the hazard
      classification as required by the European CLP regulation in category 1 versus
      category 2 was similar. The ED10 for effects warranting classification is
      proposed as the best parameter for the potency based on its independence of
      administered dose levels.

PMID- 22410177
TI  - The effects of pain, supination, and grip strength on patient-rated disability
      after operatively treated distal radius fractures.
AB  - PURPOSE: The correlation between physician-observed parameters and patient-rated
      disability in distal radius fractures is complex and poorly understood. Anecdotal
      clinical experience suggests that supination is an important factor in the return
      of functional status after distal radius fracture. To explore this relationship,
      we conducted a retrospective multivariate linear regression analysis of an
      existing patient database to evaluate the hypothesis that range of motion and
      other objective parameters are important determinants of patient-rated
      disability. METHODS: We analyzed a prospectively gathered registry of patients
      undergoing operative fixation of distal radius fractures using physical
      examination parameters measured at each follow-up visit and patient-based
      outcomes including Disabilities of the Arm, Shoulder, and Hand (DASH)
      questionnaire and visual analog scale for pain. We constructed a multivariate
      linear regression model to evaluate the association of range of motion, grip
      strength, and visual analog scale score with the DASH score. RESULTS: We analyzed
      data from 190 patients and 611 total clinic visits. Pain, grip strength, and
      supination were significantly correlated with DASH scores, controlling for all
      other factors. These 3 variables were able to predict 56% of the variability of
      the DASH score. Flexion-extension, radial-ulnar deviation, and pronation had no
      significant correlation to DASH score. CONCLUSIONS: Pain, strength, and
      supination appear to be important determinants of patient-rated outcomes after
      distal radius fracture. Pain and strength continuously improve over time up to 2
      years after surgery, whereas supination plateaus more quickly, usually within the
      first 3 to 6 months. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

PMID- 22410175
TI  - Endothelial progenitor cells and integrins: adhesive needs.
AB  - In the last decade there have been multiple studies concerning the contribution
      of endothelial progenitor cells (EPCs) to new vessel formation in different
      physiological and pathological settings. The process by which EPCs contribute to
      new vessel formation in adults is termed postnatal vasculogenesis and occurs via
      four inter-related steps. They must respond to chemoattractant signals and
      mobilize from the bone marrow to the peripheral blood; home in on sites of new
      vessel formation; invade and migrate at the same sites; and differentiate into
      mature endothelial cells (ECs) and/or regulate pre-existing ECs via paracrine or
      juxtacrine signals. During these four steps, EPCs interact with different
      physiological compartments, namely bone marrow, peripheral blood, blood vessels
      and homing tissues. The success of each step depends on the ability of EPCs to
      interact, adapt and respond to multiple molecular cues. The present review
      summarizes the interactions between integrins expressed by EPCs and their
      ligands: extracellular matrix components and cell surface proteins present at
      sites of postnatal vasculogenesis. The data summarized here indicate that
      integrins represent a major molecular determinant of EPC function, with different
      integrin subunits regulating different steps of EPC biology. Specifically,
      integrin alpha4beta1 is a key regulator of EPC retention and/or mobilization from
      the bone marrow, while integrins alpha5beta1, alpha6beta1, alphavbeta3 and
      alphavbeta5 are major determinants of EPC homing, invasion, differentiation and
      paracrine factor production. beta2 integrins are the major regulators of EPC
      transendothelial migration. The relevance of integrins in EPC biology is also
      demonstrated by many studies that use extracellular matrix-based scaffolds as a
      clinical tool to improve the vasculogenic functions of EPCs. We propose that
      targeted and tissue-specific manipulation of EPC integrin-mediated interactions
      may be crucial to further improve the usage of this cell population as a relevant
      clinical agent.

PMID- 22410178
TI  - Opioid consumption following outpatient upper extremity surgery.
AB  - PURPOSE: After elective outpatient upper extremity surgery, patients' need for
      opioid analgesic medication may be considerably less than typically dispensed.
      Our goal for this study was to evaluate pain control and quantify the amount of
      leftover pain medication. METHODS: We recruited patients scheduled for elective
      outpatient upper extremity surgery, who met the inclusion criteria, to
      participate in a phone interview 7 to 14 days after surgery. Information
      collected included age, gender, procedure performed, analgesic medication and
      regimen prescribed, satisfaction with pain control, number of tablets remaining,
      reasons for not taking medication, other analgesic medications used, payer
      classification, and any adverse drug reactions. RESULTS: A total of 287 eligible
      subjects consented to participate. Of these, 36 patients failed phone contact and
      1 patient canceled surgery, which left 250 patients who completed the study.
      Oxycodone, hydrocodone, and propoxyphene accounted for over 95% of the
      prescription medications, with adequate pain control reported by 230 (92%)
      patients. Patients most frequently received 30 pills. Patients undergoing bone
      procedures reported the highest medication use (14 pills), whereas patients
      undergoing soft tissue procedures reported the lowest use (9 pills). Over half of
      the subjects reported taking the opioid medication for 2 days or less. Medicare
      patients consumed significantly less medication (7 pills, P < .05) than patients
      covered by all other types of insurance. Overall, patients consumed a mean of 10
      opioid pills, whereas 19 pills per subject were reported unused, which resulted
      in 4,639 leftover tablets for the entire cohort. CONCLUSIONS: Our data show that
      excess opioid analgesics are made available after elective upper extremity
      surgery and could potentially become a source for diversion. A prescription of 30
      opioid pills for outpatient surgery appears excessive and unnecessary, especially
      for soft tissue procedures of the hand and wrist. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Prognostic I.

PMID- 22410179
TI  - Hand surgery: considerations in pregnant patients.

PMID- 22410180
TI  - Refractory polymyalgia rheumatica as presenting manifestation of large-vessel
      vasculitis associated to sarcoidosis. Successful response to adalimumab.
AB  - Sarcoidosis may present with musculoskeletal features or mimic rheumatic
      diseases. We report on a patient who had been initially diagnosed as having
      polymyalgia rheumatica. Because of refractory disease associated to atypical
      features such as severe inflammatory low back pain, dull and achy pain in the
      thighs, claudication of the lower limbs and bad response to corticosteroids and
      methotrexate (MTX), an 18F-fluorodeoxyglucosepositron emission tomography with CT
      (FDG PET/CT) was performed. This technique disclosed data suggestive of arteritis
      of large vessels involving the ascending, arch and descending aorta as well as
      high FDG uptake in the femoral and posterior tibial arteries of both lower
      extremities. Also, increased FDG uptake was observed in the right paratracheal,
      retrotracheal, subcarinal, gastrohepatic ligament, coeliac and right renal hilar
      lymph nodes. Four lymph nodes, taken during mediastinoscopy, confirmed a
      diagnosis of sarcoidosis. Treatment with adalimumab (40 mg every 2 weeks
      subcutaneously) along with prednisone and MTX was initiated yielding progressive
      improvement of symptoms and normalisation of laboratory abnormalities. Five
      months after the onset of adalimumab a new FDG PET/CT showed complete absence of
      uptake of lymph nodes as well as decrease of vascular FDG uptake. To our
      knowledge, this is the first patient treated with adalimumab because of a large
      vessel vasculitis in the setting of sarcoidosis refractory to conventional
      therapy. This case reinforces the claim that sarcoidosis should be considered a
      diagnostic challenge in the assessment of patients presenting with inflammatory
      musculoskeletal symptoms.

PMID- 22410182
TI  - Reuse and refurbish: a cost savings delivery model for specialized seating.
AB  - OBJECTIVES: To describe a unique specialized seating delivery model for children
      with disabilities that focuses on cost containment and environmental
      preservation. To determine whether this delivery model achieves cost containment.
      DESIGN: A retrospective cost analysis using data from billing records and annual
      statistical reports of the specialized seating program, for the 2004 to 2009
      billing period. SETTING: The specialized seating program is a service provided on
      a referral basis by the Saskatchewan Abilities Council, which is under contract
      to Saskatchewan Health. PARTICIPANTS: Pediatric patients (N=40) with physical
      disabilities (cerebral palsy, developmental delay, acquired brain injury, spinal
      cord injury, Down syndrome, other) who were referred, assessed, and met inclusion
      criteria. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Relative cost (in
      Canadian dollars) of providing units with recycled components compared with
      purchasing new units. RESULTS: The average cost of a used wheelchair was Can
      $698.11. The average cost of a new chair was $2143.69, leading to an average
      savings per chair of $1445.58. Of the 49 chairs issued, this resulted in a total
      cost savings of $85,393.97. When labor costs were taken into account
      ($50,060.26), the savings amounted to $35,333.71. Overall cost reduction was
      41.3%. CONCLUSIONS: A retrospective analysis shows evidence of cost containment.
      Long-term sustainability of the program requires ongoing analysis of the cost and
      environmental advantages of a recycling program and review of benefits provided
      in relation to the ability to meet patient needs. This delivery model does
      incorporate accountability and a policy framework, which could serve as a model
      for other centers.

PMID- 22410183
TI  - Pyranine-induced self-assembly of colloidal structures using poly(allylamine
      hydrochloride).
AB  - Complexes of dyes and polyelectrolytes have found widespread use in a variety of
      functional materials and interfaces. Here it is found that upon mixing the
      anionic dye pyranine and a cationic polyelectrolyte, poly(allylamine
      hydrochloride), two different colloidal structures may form. Above a certain
      concentration of anionic dye, crosslinking of the polyelectrolyte is initiated,
      and the formation of sheet-like colloidal structures was observed. Addition of
      hydroxyl ions resulted in the formation of micron-sized spherical colloids. It
      was also found that the colloidal shape transition was accompanied by a
      significant red-shift in the fluorescence emission. Combining fluorescence
      measurements with studies of the particle size with time, it was found that red
      shift was related to the crosslinking of the dye and the polyelectrolyte, and was
      not influenced significantly by the aggregation and particle growth. Further
      information about the colloidal behavior and stability was obtained by letting
      droplets dry and follow the kinetics of this process. It was found that the
      particles collapsed near the contact line and formed a ring deposit, in agreement
      with previous studies. However, unlike previous studies, the thickness of the
      ring deposit did not grow significantly with time, due to the peculiar process of
      formation found here.

PMID- 22410184
TI  - A three parameter description of the structure of diffusion limited cluster
      fractal aggregates.
AB  - A three parameter description of fractal aggregates is derived from the pair
      correlation function of the monomeric units that compose the aggregate. The
      parameters describe the mass fractal scaling with linear size (the fractal
      dimension), the packing fraction density of the spherical monomers, and the
      overall shape of the aggregates. Values for these three parameters are determined
      for diffusion limited cluster aggregates (DLCAs) in three dimensions. The effects
      of these parameters are found in terms of measureable quantities in both real and
      reciprocal space.

PMID- 22410181
TI  - Diagnostic tools in Rhinology EAACI position paper.
AB  - This EAACI Task Force document aims at providing the readers with a
      comprehensive and complete overview of the currently available tools for
      diagnosis of nasal and sino-nasal disease. We have tried to logically order the
      different important issues related to history taking, clinical examination and
      additional investigative tools for evaluation of the severity of sinonasal
      disease into a consensus document. A panel of European experts in the field of
      Rhinology has contributed to this consensus document on Diagnostic Tools in
      Rhinology.

PMID- 22410185
TI  - Developing lay health worker policy in South Africa: a qualitative study.
AB  - BACKGROUND: Over the past half decade South Africa has been developing,
      implementing and redeveloping its Lay Health Worker (LHW) policies. Research
      during this period has highlighted challenges with LHW programme implementation.
      These challenges have included an increased burden of care for female LHWs. The
      aim of this study was to explore contemporary LHW policy development processes
      and the extent to which issues of gender are taken up within this process.
      METHODS: The study adopted a qualitative approach to exploring policy development
      from the perspective of policy actors. Eleven policy actors (policy makers and
      policy commentators) were interviewed individually. Data from the interviews were
      analysed thematically. RESULTS: Considerations of LHW working conditions drove
      policy redevelopment. From the interviews it seems that gender as an issue never
      reached the policy making agenda. Although there was strong recognition that the
      working conditions of LHWs needed to be improved, poor working conditions were
      not necessarily seen as a gender concern. Our data suggests that in the process
      of defining the problem which the redeveloped policy had to address, gender was
      not included. There was no group or body who brought the issue of gender to the
      attention of policy developers. As such the issue of gender never entered the
      policy debates. These debates focused on whether it was appropriate to have LHWs,
      what LHW programme model should be adopted and whether or not LHWs should be
      incorporated into the formal health system. CONCLUSION: LHW policy redevelopment
      focused on resolving issues of LHW working conditions through an active process
      involving many actors and strong debates. Within this process the issue of gender
      had no champion and never reached the LHW policy agenda. Future research may
      consider how to incorporate the voices of ordinary women into the policy making
      process.

PMID- 22410186
TI  - Population-based surveillance of extensively drug-resistant tuberculosis in
      Shandong Province, China.
AB  - To investigate the prevalence of extensively drug-resistant tuberculosis (XDR-TB)
      in Chinese populations, we analyzed the drug resistance profiles of 1787
      Mycobacterium tuberculosis isolates through a population-based surveillance
      project in Shandong Province, China. We found  330 (18.5%; 95%CI 16.1-20.3)
      isolates resistant to >=1 first-line drug and 65 (3.6%; 95%CI 2.9-4.6) multidrug
      resistant (MDR) isolates, of which 13 (20.0%; 95%CI 11.9-31.4) were XDR; 47/65
      MDR-TB isolates (70.8%; 95%CI 58.2-81.4) were resistant to fluoroquinolones.  Our
      results indicate that inadequate application of second-line anti-tuberculosis
      drugs has caused increased prevalence of XDR-TB in certain Chinese populations.

PMID- 22410187
TI  - Wetlands in The Netherlands and New Zealand: optimising biodiversity and carbon
      sequestration during urbanisation.
AB  - The halting of biodiversity decline of wetlands necessitates ecosystem
      protection, restoration and re-creation of all wetland types preferably in all
      suitable landscapes. As peat wetlands (bogs and fens) are superior as carbon
      stores, and because of their rarity they have a higher biodiversity value
      relative to other wetland types, they need to be prioritised for protection and
      restoration. The hydrological, pH, and nutrient conditions essential to each type
      of wetland that need to be understood and provided for during development are
      discussed for The Netherlands' and New Zealand. Case studies describe freshwater
      wetland management and challenges during urbanisation in the Stad van de Zon and
      Blauwestad in The Netherlands, and in the Styx valley and Pegasus in
      Christchurch, New Zealand. A summary of the history of urbanisation and wetland
      destruction, and of biodiversity management for each country provides a context
      for the case studies. These case studies demonstrate the degree to which the
      relative values of bogs, fens and swamps, with respect to biodiversity and carbon
      sequestration, are understood and managed using diverse protection measures,
      within the boundaries of new urban developments and in adjacent ecological
      corridors.

PMID- 22410188
TI  - Accumulation of potentially toxic elements in road deposited sediments in
      residential and light industrial neighborhoods of Singapore.
AB  - Road deposited sediments (RDS) are a valuable environmental medium for
      characterizing contaminant levels in urban areas; and their associated
      potentially toxic elements (PTEs) can directly impact both human and aquatic
      health. In this study, RDS were collected from 15 co-located industrial and
      residential roads throughout Singapore to determine the effect of land use on
      contaminant levels. A second pilot study was designed to quantify the efficiency
      of road sweeping in removing different RDS grain size fractions from industrial
      and residential roads. The fine fraction (<63 MUm) of all RDSs was analyzed for
      over 40 elements. Eleven elements that reflect geogenic and anthropogenic sources
      were examined in detail (Al, Co, Cr, Cu, Fe, Ni, Pb, Sb, Sc, Si, and Zn).
      Industrial RDS had statistically higher concentrations of Co, Cr, Fe, and Ni than
      residential RDS. Potentially toxic elements Cu, Pb, Sb, and Zn were enriched >10
      fold at all locations compared to upper continental crust values. Concentrations
      of Cu, Pb and Zn exceeded aquatic sediment probable effect concentration levels,
      suggesting they could generate a toxic response in bottom-dwelling aquatic
      organisms. Traffic was equally heavy at both industrial and residential sites,
      but large trucks and machinery comprised a larger proportion of the traffic in
      the industrial areas. Traffic was not significantly correlated with the PTE
      (i.e., Cu, Pb, Sb and Zn) concentrations. Plausible anthropogenic contaminant
      sources include vehicles (e.g., brake and tire wear, vehicle emissions) and
      several industrial activities including metal works, oil processing, and waste
      incineration. Street sweeping was effective in removal of large organic debris
      and inorganic RDS, but it was ineffective in removing the geochemically important
      fraction, i.e., <125 MUm.

PMID- 22410189
TI  - The role of diffusion in ferritin-induced relaxation enhancement of protons.
AB  - The influence of proton diffusion on nuclear magnetic resonance (NMR) relaxation
      was investigated in the presence of horse spleen ferritin at 7 T. Binary mixtures
      of water and glycerol were used to control diffusion within the range of 0.6-2.0
      * 10(-9)m(2)/s, which was confirmed by pulsed gradient techniques. The effect of
      chemical exchange by hydrolysis between water and glycerol on relaxation was
      characterized with Carr-Purcell-Meiboom-Gill (CPMG) dispersion experiments. The
      relaxation rate enhancement of the protons due to ferritin was found to be
      inversely proportional to the diffusion coefficient. The enhancement increased by
      a factor of 3.6 over the range of diffusion coefficients, while the hydroxyl
      proton concentration decreased by a factor of 1.3. This result is in disagreement
      with the proton exchange dephasing model, which is independent of diffusion but
      predicts an inverse dependence on the hydroxyl concentration. Our data indicate
      that the role of diffusion dominates and must be considered when relaxation rates
      are used to determine iron concentration in vivo.

PMID- 22410190
TI  - A novel hysteroscopic technique for the accurate biopsy of decidua parietalis and
      basalis.
AB  - BACKGROUND: Discrepancies in the results from studies of early events in human
      trophoblast invasion of decidua have been acknowledged and are attributed largely
      to deficiencies in the accuracy of sampling of the decidual tissue used in the
      research. We describe a novel technique of biopsy of decidua parietalis and
      basalis that overcomes the issue of accuracy of site of the biopsy. METHODS &
      RESULTS: The technique is applicable to pregnancies undergoing first trimester
      surgical termination. Following cervical dilatation, a rigid hysteroscope is
      introduced into the cervical canal. The pressure of the saline distending medium
      shears the membranes of the gestation sac away from the decidua parietalis,
      leaving the pregnancy suspended at the site of the early placenta (the decidual
      basalis). Under direct vision a biopsy forceps is used to sample the decidua
      parietalis, and then the forceps is introduced beneath the gestation sac to
      sample the decidua basalis. Morphological and immunohistochemical studies have
      confirmed the accuracyof site and adequacy of the samples, with a 40% myometrial
      spiral artery success rate. CONCLUSION: This is a simple novel technique of
      decidual biopsy under direct vision which allows for high accuracy of the site of
      biopsy material, and therefore has the potential to revolutionize research on
      trophoblast-decidua interactions during the critical early stages of human
      pregnancy.

PMID- 22410191
TI  - Medical advice and diabetes self-management reported by Mexican-American, Black-
      and White-non-Hispanic adults across the United States.
AB  - BACKGROUND: Diabetes has reached epidemic proportions in the United States,
      particularly among minorities, and if improperly managed can lead to medical
      complications and death. Healthcare providers play vital roles in communicating
      standards of care, which include guidance on diabetes self-management. The
      background of the client may play a role in the patient-provider communication
      process. The aim of this study was to determine the association between medical
      advice and diabetes self care management behaviors for a nationally
      representative sample of adults with diabetes. Moreover, we sought to establish
      whether or not race/ethnicity was a modifier for reported medical advice received
      and diabetes self-management behaviors. METHODS: We analyzed data from 654 adults
      aged 21 years and over with diagnosed diabetes [130 Mexican-Americans; 224 Black
      non-Hispanics; and, 300 White non-Hispanics] and an additional 161 with
      'undiagnosed diabetes' [N = 815(171 MA, 281 BNH and 364 WNH)] who participated in
      the National Health and Nutrition Examination Survey (NHANES) 2007-2008. Logistic
      regression models were used to evaluate whether medical advice to engage in
      particular self-management behaviors (reduce fat or calories, increase physical
      activity or exercise, and control or lose weight) predicted actually engaging in
      the particular behavior and whether the impact of medical advice on engaging in
      the behavior differed by race/ethnicity. Additional analyses examined whether
      these relationships were maintained when other factors potentially related to
      engaging in diabetes self management such as participants' diabetes education,
      sociodemographics and physical characteristics were controlled. Sample weights
      were used to account for the complex sample design. RESULTS: Although medical
      advice to the patient is considered a standard of care for diabetes,
      approximately one-third of the sample reported not receiving dietary, weight
      management, or physical activity self-management advice. Participants who
      reported being given medical advice for each specific diabetes self-management
      behaviors were 4-8 times more likely to report performing the corresponding
      behaviors, independent of race. These results supported the ecological model with
      certain caveats. CONCLUSIONS: Providing standard medical advice appears to lead
      to diabetes self-management behaviors as reported by adults across the United
      States. Moreover, it does not appear that race/ethnicity influenced reporting
      performance of the standard diabetes self-management behavior. Longitudinal
      studies evaluating patient-provider communication, medical advice and diabetes
      self-management behaviors are needed to clarify our findings.

PMID- 22410192
TI  - Kinematic and kinetic modifications in walking pattern of hip osteoarthritis
      patients induced by intra-articular injections of hyaluronic acid.
AB  - BACKGROUND: A growing body of evidence points to the efficacy of intra-articular
      injections of hyaluronic acid, in dealing with pain and function in hip
      osteoarthritis. To date, however, no data exist as to this treatment's effect on
      walking pattern. METHODS: We performed a prospective, open study in order to
      verify, in a group of 20 hip osteoarthritis patients (12 men, 8 women, mean age
      60.5, range 47-73), the clinical effects of 3 intra-articular injections of 2 ml
      of hyaluronic acid in the hip (1/week) in terms of pain and function at 1 (T1), 3
      (T2) and 6-month (T3) follow-ups, as well as changes in the kinematics and
      kinetics of gait at 6-month follow-up. FINDINGS: Pain as measured with visual
      analog scale significantly dropped after this procedure (P<0.0001). A significant
      improvement was noted regarding stiffness (P=0.005) and disability (P=0.04), as
      measured by the Western Ontario and McMaster Universities osteoarthritis index.
      As regards gait analysis, patients at T3 walked with higher cadence (P=0.004) and
      stride length (P=0.02) compared to T0. Moreover, a significant increase for the
      pelvic tilt at heel contact (P=0.0004) and for hip flexion-extension moment at
      loading response sub-phases of gait cycle (P=0.02) was noted at T3.
      INTERPRETATION: In line with current literature, our patients display clinical
      improvement 6 months after intra-articular injections of hyaluronic acid,
      accompanied by changes in walking pattern, as measured by instrumental gait
      analysis. The kinematic and kinetic changes observed may be the consequence of
      the therapeutic effect of intra-articular injections of hyaluronic acid.

PMID- 22410193
TI  - Investigation of the antidyskinetic site of action of metabotropic and ionotropic
      glutamate receptor antagonists. Intracerebral infusions in 6-hydroxydopamine
      lesioned rats with levodopa-induced dyskinesia.
AB  - Long-term levodopa replacement therapy in Parkinson's disease is confounded by
      abnormal involuntary movements, known as levodopa induced dyskinesia (LID).
      Dysfunctional glutamatergic neurotransmission has been implicated in the
      pathogenesis of LID making metabotropic and ionotropic glutamate receptors
      attractive novel therapeutic targets. The objective of the present study was to
      investigate the antidyskinetic site of action of different glutamate receptor
      antagonists in the brain. For that purpose, metabotropic glutamate subtype 5 (3
      ((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine hydrochloride, MTEP), NMDA NR2B
      selective ((aR,bS)-a-(4-Hydroxyphenyl)-b-methyl-4-(phenylmethyl)-1
      piperidinepropanol maleate, Ro 25-6981) and AMPA (2,3-Dioxo-6-nitro-1,2,3,4
      tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt, NBQX) receptor
      antagonists or saline were administered by intracerebral infusion in the caudate
      putamen (CPu), the substantia nigra zona reticulata (SNr) or the subthalamic
      nucleus (STN) of 6-hydroxydopamine-lesioned rats exhibiting LID. Dyskinesia was
      assessed with the modified version of the rat Abnormal Involuntary Movements
      scale (AIMS). Ro 25-6981 and to a lesser extent NBQX improved dyskinesia (82% and
      19% reduction in AIM score respectively) after infusion in the caudate-putamen.
      None of the three drugs managed to noticeably reduce AIM score after infusion in
      the SNr. MTEP was the only drug that produced a reduction in AIM score (48%) when
      infused in STN. In conclusion, while the striatum proved important in the
      antidyskinetic action of NMDA and AMPA receptor antagonists, the results of this
      study highlight also the importance of the metabotropic glutamate receptors that
      reside in the STN as therapeutic targets in the treatment of LID.

PMID- 22410194
TI  - Association of muscarinic M3 receptors and Kir6.1 with caveolae in human detrusor
      muscle.
AB  - Caveolae are 50-100 nm large membrane invaginations that play a role in cellular
      signaling. The aim of the present study was to assess whether muscarinic M3
      receptors and the K(ATP) channel subunit Kir6.1 are associated with human
      detrusor caveolae, and to pharmacologically assess the relevance of this
      organization for contractility. Detrusor strips were dissected and used in
      ultrastructural, biochemical and mechanical studies. Caveolae were manipulated by
      cholesterol desorption using mbetacd (methyl-beta-cyclodextrin). Mbetacd
      disrupted caveolae and caused a cholesterol-dependent ~3-fold rightward shift of
      the concentration-response curve for the muscarinic receptor agonist carbachol.
      The effect of mbetacd was inhibited by the K(ATP) blockers glibenclamide,
      repaglinide and PNU-37883, and it was mimicked by the K(ATP) activator
      levcromakalim. Immunoelectron microscopy showed muscarinic M3 receptors and
      Kir6.1 to be enriched in caveolae. In conclusion, pharmacological K(ATP) channel
      inhibition antagonizes the effect of caveolae disruption on muscarinic
      contractility in the human detrusor, and the K(ATP) channel subunit Kir6.1 co
      localizes with M3 receptors in caveolae.

PMID- 22410195
TI  - Developing indicators of pattern identification in patients with stroke using
      traditional Korean medicine.
AB  - BACKGROUND: The traditional Korean medical diagnoses employ pattern
      identification (PI), a diagnostic system that entails the comprehensive analysis
      of symptoms and signs. The PI needs to be standardized due to its ambiguity.
      Therefore, this study was performed to establish standard indicators of the PI
      for stroke through the traditional Korean medical literature, expert consensus
      and a clinical field test. METHODS: We sorted out stroke patterns with an expert
      committee organized by the Korean Institute of Oriental Medicine. The expert
      committee composed a document for a standardized pattern of identification for
      stroke based on the traditional Korean medical literature, and we evaluated the
      clinical significance of the document through a field test. RESULTS: We
      established five stroke patterns from the traditional Korean medical literature
      and extracted 117 indicators required for diagnosis. The indicators were
      evaluated by a field test and verified by the expert committee. CONCLUSIONS: This
      study sought to develop indicators of PI based on the traditional Korean medical
      literature. This process contributed to the standardization of traditional Korean
      medical diagnoses.

PMID- 22410196
TI  - Cyanotic episodes in an infant with known situs inversus: indications for an
      apparent life-threatening event evaluation.

PMID- 22410198
TI  - Mitochondrial quality control: an integrated network of pathways.
AB  - Mitochondria are organelles of eukaryotic cells with various functions. Best
      known is their role in energy transduction leading to the formation of ATP. As
      byproducts of this process, reactive oxygen species (ROS) are formed that can
      damage different types of molecules leading to mitochondrial dysfunction.
      Different quality control (QC) mechanisms keep mitochondria functional. Although
      several components involved in mitochondrial QC have been characterized in some
      detail, others remain to be integrated into what is currently emerging as a
      hierarchical network of interacting pathways. The elucidation of this network
      holds the key to the understanding of complex biological processes such as aging
      and the development of age-related diseases.

PMID- 22410197
TI  - Molecular underpinnings of centromere identity and maintenance.
AB  - Centromeres direct faithful chromosome inheritance at cell division but are not
      defined by a conserved DNA sequence. Instead, a specialized form of chromatin
      containing the histone H3 variant, CENP-A, epigenetically specifies centromere
      location. We discuss current models where CENP-A serves as the marker for the
      centromere during the entire cell cycle in addition to generating the
      foundational chromatin for the kinetochore in mitosis. Recent elegant experiments
      have indicated that engineered arrays of CENP-A-containing nucleosomes are
      sufficient to serve as the site of kinetochore formation and for seeding
      centromeric chromatin that self-propagates through cell generations. Finally,
      recent structural and dynamic studies of CENP-A-containing histone complexes -
      before and after assembly into nucleosomes - provide models to explain underlying
      molecular mechanisms at the centromere.

PMID- 22410199
TI  - The German Environmental Survey for Children (GerES IV): reference values and
      distributions for time-location patterns of German children.
AB  - Children's time-location patterns are important determinants of environmental
      exposure and other health-relevant factors. Building on data of the German
      Environmental Survey for Children (GerES IV), our study aimed at deriving
      reference values and distributions for time-location patterns of 3-14-year-old
      German children. We also investigated if GerES IV data are appropriate for
      evaluating associations with children's health determinants by linking them to
      data of the National Health Interview and Examination Survey for Children and
      Adolescents (KiGGS). Parents reported on the time their children usually spend at
      home, in other indoor environments, and outdoors. This information was
      characterized by statistical parameters, which were also calculated for different
      strata concerning socio-demography and the residential environment. Consequently,
      group differences were evaluated by t-tests and univariate ANOVA. Reference
      distributions were fitted to the time-location data by a Maximum Likelihood
      approach to make them also useable in probabilistic exposure modeling. Finally,
      associations between data on the children's physical activity as well as body
      weight and their outdoor time were investigated by bivariate correlation analysis
      and cross tabulation. On daily average, German children spend 15 h and 31 min at
      home, 4 h and 46 min in other indoor environments, and 3 h and 43 min outdoors.
      Time spent at home and outdoors decreases with age while time spent in other
      indoor environments increases. Differences in time-location patterns were also
      observed for the socio-economic status (SES) and immigration status. E.g.,
      children with a high SES spend 24 min less outdoors than low SES children.
      Immigrants spend on daily average 20 min more at home and 15 min less outdoors
      than non-immigrant children. Outdoor time was associated with parameters of the
      residential environment like the building development. Children living in 1- or 2
      family houses spend more time outdoors than children living in building blocks (3
      h 48 min vs. 3 h 29 min). Physical activity correlates with outdoor time. For
      children with diminished age-specific outdoor time, a higher prevalence of
      obesity was observed (odds ratio: 3.2, 95% CI: 1.5-7.1). GerES IV provides a
      compilation of current time-location reference values and distributions on German
      children. This data hint to substantial differences in time-location patterns
      within the population to be considered in environmental health risk assessment.

PMID- 22410200
TI  - Effect of acute hyperventilation on the venous-arterial PCO2 difference.

PMID- 22410201
TI  - One-year clinical and radiological evolution of a patient with refractory
      Takayasu's arteritis under treatment with tocilizumab.
AB  - A 28-year-old patient with Takayasu's arteritis (TA) failed to respond to high
      doses of prednisone in combination with methotrexate, pulses of cyclophosphamide
      and methylprednisolone, azathioprine, mycophenolate mofetil, adalimumab and
      monthly infusions of infliximab 5 mg/kg. After the beginning of tocilizumab
      therapy (4-8 mg/kg at monthly infusions), an impressive improvement in clinical
      and laboratory parameters of disease activity occurred, allowing the reduction of
      prednisone dose from 30 to 5 mg/day. However, after the 8th dose the patient
      developed symptoms of vertebrobasilar insufficiency, despite maintaining a good
      clinical condition and normal values of inflammatory markers. Angio-computed
      tomography repeated at one year of therapy showed reduction in aortic wall
      thickness, but also narrowing of the luminal diameters of the right subclavian,
      renal arteries, and left vertebral artery. Therefore, despite a significant
      clinical and laboratory improvement, vascular disease may progress in aortic
      branches in TA patients under tocilizumab therapy.

PMID- 22410202
TI  - Performance of a multianalyte test as an aid for the diagnosis of ovarian cancer
      in symptomatic women.
AB  - BACKGROUND: Concomitant with the development of in vitro diagnostic multivariate
      index assays (IVDMIAs) to improve the diagnostic efficiency of ovarian cancer
      detection is the need to identify appropriate biostatistical approaches to assess
      improvements in risk predication. In this study, we assessed the utility of three
      different approaches for comparing diagnostic efficiency of an ovarian cancer
      multivariate assay in a retrospective case--control phase 2 biomarker trial. The
      control cohort included both disease-free women and women with benign
      gynecological conditions to more accurately reflect the target population of
      symptomatic women. METHODS: The study cohort comprised plasma samples from 244
      healthy controls, 223 women with benign gynecological conditions, 53 borderline
      ovarian cancer cases and 222 women with malignant epithelial ovarian cancer. A
      multivariate classification model was developed that incorporated plasma
      concentrations of CA125, C-reactive protein (CRP), serum amyloid-A (SAA),
      interleukin-6 (IL6) and interleukin-8 (IL8) that were measured using in vitro
      diagnostics assays on medical device approved clinical analysers. The posterior
      probability values derived from the implemented algorithm were used for
      comparisons of the diagnostic performance between the multianalyte panel and
      CA125 using multiple methods; area under the curve (AUC) of the receiver
      operating characteristics curve, integrated discrimination improvement (IDI) and
      net reclassification improvement (NRI). RESULTS: Each of the biomarkers displayed
      significantly elevated plasma concentrations in malignant ovarian cancer patients
      compared with either benign or control subjects. For the discrimination of
      borderline and malignant ovarian cancer from control and benign subjects, the
      multivariate classification model showed a significantly greater AUC than that
      for CA125 alone (88.4% versus 84.3%, respectively, p < 0.001). At a posterior
      probability threshold of 0.5, the IVDMIA delivered a specificity of 92.3% and a
      sensitivity of 76.4%. When set at a specificity of 95%, the multimarker
      diagnostic delivered a sensitivity of 69.5% compared with 62.5% for CA125.
      Enhanced diagnostic performance of the IVDMIA over the use of CA125 alone was
      confirmed statistically by alternative comparisons using IDI and NRI.
      CONCLUSIONS: This study confirms in an independent sample set that a blood-based
      multianalyte assay has significant advantages over CA125 for distinguishing
      symptomatic women with borderline and malignant ovarian cancer from controls or
      those with benign disease.

PMID- 22410203
TI  - Quantifying motion for pancreatic radiotherapy margin calculation.
AB  - BACKGROUND AND PURPOSE: Pancreatic radiotherapy (RT) is limited by uncertain
      target motion. We quantified 3D patient/organ motion during pancreatic RT and
      calculated required treatment margins. MATERIALS AND METHODS: Cone-beam computed
      tomography (CBCT) and orthogonal fluoroscopy images were acquired post-RT
      delivery from 13 patients with locally advanced pancreatic cancer. Bony setup
      errors were calculated from CBCT. Inter- and intra-fraction fiducial
      (clip/seed/stent) motion was determined from CBCT projections and orthogonal
      fluoroscopy. RESULTS: Using an off-line CBCT correction protocol, systematic
      (random) setup errors were 2.4 (3.2), 2.0 (1.7) and 3.2 (3.6)mm laterally (left
      right), vertically (anterior-posterior) and longitudinally (cranio-caudal),
      respectively. Fiducial motion varied substantially. Random inter-fractional
      changes in mean fiducial position were 2.0, 1.6 and 2.6mm; 95% of intra
      fractional peak-to-peak fiducial motion was up to 6.7, 10.1 and 20.6mm,
      respectively. Calculated clinical to planning target volume (CTV-PTV) margins
      were 1.4 cm laterally, 1.4 cm vertically and 3.0 cm longitudinally for 3D
      conformal RT, reduced to 0.9, 1.0 and 1.8 cm, respectively, if using 4D planning
      and online setup correction. CONCLUSIONS: Commonly used CTV-PTV margins may
      inadequately account for target motion during pancreatic RT. Our results indicate
      better immobilisation, individualised allowance for respiratory motion, online
      setup error correction and 4D planning would improve targeting.

PMID- 22410204
TI  - Outcomes of HPV-related oropharyngeal cancer patients treated by radiotherapy
      alone using altered fractionation.
AB  - PURPOSE: To report outcome of HPV-related [HPV(+)] oropharyngeal cancer (OPC)
      managed predominantly by altered-fractionation radiotherapy-alone (RT-alone).
      METHODS: OPCs treated with RT-alone (n = 207) or chemoradiotherapy (CRT) (n =
      151) from 2001 to 2008 were included. Overall survival (OS), local (LC), regional
      (RC) and distant (DC) control were compared for HPV(+) vs. HPV-unrelated [HPV(
      )], by RT-alone vs. CRT, and by smoking pack-years (<= 10 vs. >10). Multivariate
      analysis identified predictors. RESULTS: HPV(+) (n = 277) had better OS (81% vs.
      44%), LC (93% vs. 76%), RC (94% vs. 79%) (all p < 0.01) but similar DC (89% vs.
      86%, p = 0.87) vs. HPV(-) (n = 81). HPV(+) stage IV CRT (n = 125) had better OS
      (89% vs. 70%, p < 0.01), but similar LC (93% vs. 90%, p = 0.41), RC (94% vs. 90%,
      p = 0.31) and DC (90% vs. 83%, p = 0.22) vs. RT-alone (n = 96). Both HPV(+) RT
      alone (n = 37) and CRT (n = 67) stage IV minimal smokers had favorable OS (86%
      vs. 88%, p = 0.45), LC (95% vs. 92%, p = 0.52), RC (97% vs. 93%, p = 0.22), and
      DC (92% vs. 86%, p = 0.37). RT-alone and heavy-smoking were independent
      predictors for lower OS but not CSS in multivariate analysis. CONCLUSIONS:
      Overall, HPV(+) RT-alone stage IV demonstrated lower survival but comparable
      disease control vs. CRT, but no difference was apparent among minimal smokers.

PMID- 22410205
TI  - In silico cloning and characterization of the TGA (TGACG MOTIF-BINDING FACTOR)
      transcription factors subfamily in Carica papaya.
AB  - The TGA transcription factors belong to the subfamily of bZIP group D that play a
      major role in disease resistance and development. Most of the TGA identified in
      Arabidopsis interact with the master regulator of SAR, NPR1 that controls the
      expression of PR genes. As a first approach to determine the possible involvement
      of these transcription factors in papaya defense, we characterized Arabidopsis
      TGA orthologs from the genome of Carica papaya cv. SunUp. Six orthologs CpTGA1 to
      CpTGA6, were identified. The predicted CpTGA proteins were highly similar to
      AtTGA sequences and probably share the same DNA binding properties and
      transcriptional regulation features. The protein sequences alignment evidenced
      the presence of conserved domains, characteristic of this group of transcription
      factors. The phylogeny showed that CpTGA evolved into three different subclades
      associated with defense and floral development. This is the first report of basal
      expression patterns assessed by RT-PCR, from the whole subfamily of CpTGA members
      in different tissues from papaya cv. Maradol mature plants. Overall, CpTGA1,
      CpTGA3 CpTGA6 and CpTGA4 showed a basal expression in all tissues tested; CpTGA2
      expressed strongly in all tissues except in petioles while CpTGA5 expressed only
      in petals and to a lower extent in petioles. Although more detailed studies in
      anthers and other floral structures are required, we suggest that CpTGA5 might be
      tissue-specific, and it might be involved in papaya floral development. On the
      other hand, we report here for the first time, the expression of the whole family
      of CpTGA in response to salicylic acid (SA). The expression of CpTGA3, CpTGA4 and
      CpTGA6 increased in response to SA, what would suggest its involvement in the SAR
      response in papaya.

PMID- 22410206
TI  - Apathy in currently nondepressed patients treated with a SSRI for a major
      depressive episode: outcomes following randomized switch to either duloxetine or
      escitalopram.
AB  - Apathy in the context of treated major depressive disorder (MDD) is a common but
      understudied symptom. This multicenter, double-blind, randomized study
      investigated whether switching from a selective serotonin reuptake inhibitor
      (SSRI) to a serotonin-norepinephrine reuptake inhibitor (SNRI), compared with
      switching to another SSRI, improved apathy symptoms in patients who had been
      treated with a SSRI for MDD for >= 3 months, were no longer depressed (Montgomery
      Asberg Depression Rating Scale [MADRS] total score <= 15), and continued to have
      apathy (Apathy Evaluation Scale--Clinician rated version [AES-C] total score
      >30). Following 8 weeks of treatment, both the duloxetine (SNRI, 244 patients)
      and escitalopram (SSRI, 239 patients) groups significantly improved from baseline
      on the AES-C total score (least squares mean change [standard error]: duloxetine 
      13.9 [0.54]; escitalopram -13.5 [0.54], both P < 0.001), and on the secondary
      apathy, depression, and functional outcomes. There were no significant
      differences between the two groups on any measure, including AES-C total score
      (least squares mean difference [95% confidence interval]: -0.4 [-1.87 to 1.10], P
      = 0.612; primary objective). There was a significant within-group improvement in
      apathy in the subgroup who received escitalopram before and during the study.
      There were few differences in safety between the two groups. This study did not
      support the hypothesis that switching from a SSRI to a SNRI has a beneficial
      effect on apathy symptoms. However, given the study limitations, it is possible
      that more specific targeting of the noradrenergic pathway would be of benefit.

PMID- 22410207
TI  - Contribution of spontaneous improvement to placebo response in depression: a meta
      analytic review.
AB  - OBJECTIVES: It is unknown to what degree spontaneous improvement accounts for the
      large placebo response observed in antidepressant trials for Major Depressive
      Disorder (MDD). The purpose of this study was to estimate the spontaneous
      improvement observed in treatment-seeking individuals with acute MDD by
      determining the symptom change in depressed patients assigned to wait-list
      controls in psychotherapy studies. METHOD: The databases PubMed and PsycINFO were
      searched to identify randomized, prospective studies randomizing outpatients to
      psychotherapy or a wait-list control condition for the treatment of acute MDD.
      Standardized effect sizes calculated from each identified study were aggregated
      in a meta-analysis to obtain a summary statistic for the change in depression
      scores during participation in a wait-list control. RESULTS: Ten trials enrolling
      340 participants in wait-list control conditions were identified. The estimated
      effect size for the change in depression scores during wait-list control was
      0.505 (95% CI 0.271-0.739, p < 0.001), representing an average improvement of 4
      points on the Hamilton Rating Scale for Depression. DISCUSSION: Depressed
      patients acutely experience improvement even without treatment, but spontaneous
      improvement is unlikely to account for the magnitude of placebo response
      typically observed in antidepressant trials. These findings must be interpreted
      in light of the small number wait-list control participants available for
      analysis as well as certain methodological heterogeneity in the psychotherapy
      studies analyzed.

PMID- 22410208
TI  - The relationship between age of gambling onset and adolescent problematic
      gambling severity.
AB  - The aim of this study was to characterize the association between problem
      gambling severity and multiple health, functioning and gambling variables in
      adolescents aged 13-18 stratified by age of gambling onset. Survey data in 1624
      Connecticut high school students stratified by age of gambling onset (<= 11 years
      vs. >= 12 years) were analyzed in descriptive analyses and in logistic regression
      models. Earlier age of onset was associated with problem gambling severity as
      indexed by a higher frequency of at-risk/problem gambling (ARPG). Most health,
      functioning and gambling measures were similarly associated with problem gambling
      severity in the earlier- and later-age-of-gambling-onset groups with the
      exception of participation in non-strategic forms of gambling, which was more
      strongly associated with ARPG in the earlier-onset (OR = 1.74, 95%CI = [1.26,
      2.39]) as compared to later-onset (OR = 0.94, 95%CI = [0.60, 1.48]) group
      (Interaction OR = 1.91, 95%CI = [1.18, 3.26]). Post-hoc analysis revealed that
      earlier-onset ARPG was more strongly associated with multiple forms of non
      strategic gambling including lottery (instant, traditional) and slot-machine
      gambling. The finding that problem gambling severity is more closely associated
      with multiple non-strategic forms of gambling amongst youth with earlier-onset
      gambling highlights the relevance of these types of youth gambling. The extent to
      which non-strategic forms of gambling may serve as a gateway to other forms of
      gambling or risk behaviors warrants additional study, and efforts targeting youth
      gambling should consider how best to address non-strategic gambling through
      education, prevention, treatment and policy efforts.

PMID- 22410210
TI  - Barth syndrome in a female patient.
AB  - BACKGROUND: Barth syndrome (BTHS) is an X-linked recessive disorder characterized
      by cardiomyopathy, skeletal myopathy and cyclic neutropenia in male patients. It
      is caused by mutations in the TAZ gene coding for the tafazzin, a protein
      involved in the remodeling of cardiolipin. Loss of cardiolipin in the inner
      mitochondrial membrane results in respiratory chain dysfunction. No specific
      symptom has been identified in female carriers. CASE REPORT: We report the first
      case of BTHS confirmed by TAZ gene analysis in a female patient. This girl
      experienced severe heart failure at 1-month of age. Echocardiography diagnosed
      dilated-hypokinetic and hypertrophic cardiomyopathy with noncompaction of the
      left ventricle. Initial metabolic screening was normal, except for a cyclic
      neutropenia. Respiratory chain analysis performed on skin fibroblasts revealed a
      decreased activity of complexes I, III and IV. Screening on a bloodspot showed
      abnormal monolysocardiolipin:cardiolipin ratio, later confirmed on cultured
      fibroblasts, indicative of BTHS. Genetic analyses finally confirmed the diagnosis
      of BTHS, by showing a large intragenic deletion of exons 1 through 5 in the TAZ
      gene. Cytogenetic analysis showed mosaicism for monosomy X and for a ring X
      chromosome with a large deletion of the long arm including the Xq28 region. The
      girl presented recurrent episodes of severe acute heart failure, progressive
      muscle weakness, and had a fatal septic shock at 3 years. CONCLUSION: This case
      highlights that the diagnosis of BTHS should also be suspected in female patients
      presenting a phenotype similar to affected boys. In these cases, analysis of the
      monolysocardiolipin:cardiolipin ratio in bloodspots is a rapid and sensitive
      screening tool for BTHS. However clinical expression in a carrier female requires
      hemizygosity for the mutated allele of the TAZ gene, which supposes a
      rearrangement of the TAZ gene region on the other X chromosome.

PMID- 22410209
TI  - Not all shellfish "allergy" is allergy!
AB  - The popularity of shellfish has been increasing worldwide, with a consequent
      increase in adverse reactions that can be allergic or toxic. The approximate
      prevalence of shellfish allergy is estimated at 0.5-2.5% of the general
      population, depending on degree of consumption by age and geographic regions. The
      manifestations of shellfish allergy vary widely, but it tends to be more severe
      than most other food allergens.Tropomyosin is the major allergen and is
      responsible for cross-reactivity between members of the shellfish family,
      particularly among the crustacea. Newly described allergens and subtle
      differences in the structures of tropomyosin between different species of
      shellfish could account for the discrepancy between in vitro cross-antigenicity
      and clinical cross-allergenicity. The diagnosis requires a thorough medical
      history supported by skin testing or measurement of specific IgE level, and
      confirmed by appropriate oral challenge testing unless the reaction was life
      threatening.Management of shellfish allergy is basically strict elimination,
      which in highly allergic subjects may include avoidance of touching or smelling
      and the availability of self-administered epinephrine. Specific immunotherapy is
      not currently available and requires the development of safe and effective
      protocols.

PMID- 22410211
TI  - Calcium signatures and signaling in cytosol and organelles of tobacco cells
      induced by plant defense elicitors.
AB  - Calcium signatures induced by two elicitors of plant defense reactions, namely
      cryptogein and oligogalacturonides, were monitored at the subcellular level,
      using apoaequorin-transformed Nicotiana tabacum var Xanthi cells, in which the
      apoaequorin calcium sensor was targeted either to cytosol, mitochondria or
      chloroplasts. Our study showed that both elicitors induced specific Ca(2+)
      signatures in each compartment, with the most striking difference relying on
      duration. Common properties also emerged from the analysis of Ca(2+) signatures:
      both elicitors induced a biphasic cytosolic [Ca(2+)] elevation together with a
      single mitochondrial [Ca(2+)] elevation concomitant with the first cytosolic
      [Ca(2+)] peak. In addition, both elicitors induced a chloroplastic [Ca(2+)]
      elevation peaking later in comparison to cytosolic [Ca(2+)] elevation. In
      cryptogein-treated cells, pharmacological studies indicated that IP(3) should
      play an important role in Ca(2+) signaling contrarily to cADPR or nitric oxide,
      which have limited or no effect on [Ca(2+)] variations. Our data also showed
      that, depending on [Ca(2+)] fluxes at the plasma membrane, cryptogein triggered a
      mitochondrial respiration increase and affected excess energy dissipation
      mechanisms in chloroplasts. Altogether the results indicate that cryptogein
      profoundly impacted cell functions at many levels, including organelles.

PMID- 22410212
TI  - Exposure to common food additive carrageenan leads to reduced sulfatase activity
      and increase in sulfated glycosaminoglycans in human epithelial cells.
AB  - The commonly used food additive carrageenan, including lambda (lambda), kappa
      (kappa) and iota (iota) forms, is composed of galactose disaccharides linked in
      alpha-1,3 and beta-1,4 glycosidic bonds with up to three sulfate groups per
      disaccharide residue. Carrageenan closely resembles the endogenous galactose or N
      acetylgalactosamine-containing glycosaminoglycans (GAGs), chondroitin sulfate
      (CS), dermatan sulfate (DS), and keratan sulfate. However, these GAGs have beta
      1,3 and beta-1,4 glycosidic bonds, in contrast to the unusual alpha-1,3
      glycosidic bond in carrageenan. Since sulfatase activity is inhibited by sulfate,
      and carrageenan is so highly sulfated, we tested the effect of carrageenan
      exposure on sulfatase activity in human intestinal and mammary epithelial cell
      lines and found that carrageenan exposure significantly reduced the activity of
      sulfatases, including N-acetylgalactosamine-4-sulfatase, galactose-6-sulfatase,
      iduronate sulfatase, steroid sulfatase, arylsulfatase A, SULF-1,2, and heparan
      sulfamidase. Consistent with the inhibition of sulfatase activity, following
      exposure to carrageenan, GAG content increased significantly and showed marked
      differences in disaccharide composition. Specific changes in CS disaccharides
      included increases in di-sulfated disaccharide components of CSD (2S6S) and CS-E
      (4S6S), with declines in CS-A (4S) and CS-C (6S). Specific changes in heparin
      heparan sulfate disaccharides included increases in 6S disaccharides, as well as
      increases in NS and 2S6S disaccharides. Study results suggest that carrageenan
      inhibition of sulfatase activity leads to re-distribution of the cellular GAG
      composition with increase in di-sulfated CS and with potential consequences for
      cell structure and function.

PMID- 22410213
TI  - Paclobutrazol treatment as a potential strategy for higher seed and oil yield in
      field-grown Camelina sativa L. Crantz.
AB  - BACKGROUND: Camelina (Camelina sativa L. Crantz) is a non-food oilseed crop which
      holds promise as an alternative biofuel energy resource. Its ability to grow in a
      variety of climatic and soil conditions and minimal requirements of agronomical
      inputs than other oilseed crops makes it economically viable for advanced biofuel
      production. We designed a study to investigate the effect of paclobutrazol [2RS,
      3RS)-1-(4-Chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pentan-3-ol] (PBZ),
      a popular plant growth regulator, on the seed and oil yield of Camelina sativa
      (cv. Celine). RESULTS: A field-based micro-trial setup was established in a
      randomized block design and the study was performed twice within a span of five
      months (October 2010 to February 2011) and five different PBZ treatments
      (Control: T0; 25 mg l-1: T1; 50 mg l-1: T2; 75 mg l-1: T3; 100 mg l-1: T4; 125 mg
      l-1: T5) were applied (soil application) at the time of initiation of flowering.
      PBZ at 100 mg l-1 concentration (T4) resulted in highest seed and oil yield by
      80% and 15%, respectively. The seed yield increment was mainly due to enhanced
      number of siliques per plant when compared to control. The PBZ - treated plants
      displayed better photosynthetic leaf gas exchange characteristics, higher
      chlorophyll contents and possessed dark green leaves which were
      photosynthetically active for a longer period and facilitated higher
      photoassimilation. CONCLUSION: We report for the first time that application of
      optimized PBZ dose can be a potential strategy to achieve higher seed and oil
      yield from Camelina sativa that holds great promise as a biofuel crop in future.

PMID- 22410214
TI  - Salmonella prevalence and antimicrobial susceptibility from the National Animal
      Health Monitoring System Swine 2000 and 2006 studies.
AB  - Concern about Salmonella contamination of food is compounded by fear that
      antimicrobials traditionally used to combat the infection will become useless due
      to rising antibiotic resistance. Livestock, in particular swine, often are blamed
      for illnesses caused by Salmonella  and for increasing antibiotic resistance due
      to use of antibiotics in pigs. As part of the National Animal Health Monitoring
      System Swine 2000 and 2006 studies, swine fecal samples were cultured for
      Salmonella. These samples were collected from 123 operations in 17 states in 2000
      and  from 135 operations in 17 states in 2006. At each operation, 50 and 60 fecal
      samples were collected from late finisher pig pens in 2000 and 2006,
      respectively. Salmonella isolates were characterized to determine serogroup and
      serotype and were tested for susceptibility to a panel of  17 and 15
      antimicrobial drugs in 2000 and 2006, respectively. A total of 5,470 and 7,788
      samples were cultured for Salmonella in 2000 and 2006, respectively. Overall,
      6.2% of the samples and 34.2% of the farms were positive for Salmonella in 2000.
      In 2006, 7.2% of the samples  and 52.6% of the farms were positive. Salmonella
      Derby, Salmonella Typhimurium var. 5- (formerly Salmonella Typhimurium var.
      Copenhagen), and Salmonella Agona were the three serotypes most often recovered
      in both study years. The most common antimicrobial  resistance pattern for
      Salmonella Derby in the two study years was resistance to streptomycin,
      sulfisoxazole, and tetracycline. Most isolates were resistant to tetracycline,
      sulfisoxazole, and streptomycin in both study years. The proportion of Salmonella
      isolates that were susceptible  to all antimicrobials (pansusceptible) was 38.1%
      in 2000 and 20.4% in 2006. The proportion of Salmonella isolates that were
      resistant to three or more antimicrobials (multidrug resistant) was similar in
      2000 and in 2006 (52.8 and 57.7%, respectively).

PMID- 22410215
TI  - Investigation of rpoS and dps genes in sodium hypochlorite resistance of
      Salmonella Enteritidis SE86 isolated from foodborne illness outbreaks in southern
      Brazil.
AB  - In Rio Grande do Sul, southern Brazil, Salmonella Enteritidis is one of the
      principal microorganisms responsible for foodborne disease. The present study was
      conducted to compare the sodium hypochlorite resistance of Salmonella Enteritidis
      SE86 with that of other strains  of Salmonella Enteritidis isolated from
      different regions of the world and to investigate the involvement of the rpoS and
      dps genes in resistance to this disinfectant. We tested five Salmonella
      Enteritidis wild-type (WT) strains isolated from different countries,  two mutant
      strains of Salmonella Enteritidis SE86, and two tagged (3XFLAG) strains of
      Salmonella Enteritidis SE86 for their resistance to sodium hypochlorite (200
      ppm). The survival of the WT and attenuated strains was determined based on
      bacterial counts, and tagged proteins  (Dps and RpoS) were detected by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting with anti
      FLAG antibodies. None of the WT strains of Salmonella Enteritidis were totally
      inactivated after 20 min. The SE86 strain lacking dps was more sensitive  to
      sodium hypochlorite than was the WT SE86 strain, with a 2-log reduction in counts
      after 1 min. The RpoS and Dps proteins were actively expressed under the
      conditions tested, indicating that in Salmonella Enteritidis SE86 these genes,
      which are expressed when in contact with sodium  hypochlorite, are related to
      oxidative stress.

PMID- 22410216
TI  - Propylparaben sensitizes heat-resistant Salmonella Enteritidis and Salmonella
      Oranienburg to thermal inactivation in liquid egg albumen.
AB  - Propyl p-hydroxybenzoic acid (propylparaben [PRPA]) is a phenolic antioxidant,
      known to occur in nature and used as a microbiostat in foods, feeds,
      pharmaceuticals, cosmetics, and medications. The U.S. Department of Agriculture,
      Food Safety and Inspection Service (FSIS) requires  that liquid egg white (LEW)
      be pasteurized at 56.7 degrees C for 3.5 min. This study evaluated the effects of
      PRPA on the pasteurization sensitivity of Salmonella in LEW. When LEW (pH 7.8)
      was pasteurized under FSIS conditions, salmonellae declined by 0.5, 4.6, 4.5, >
      7.0, and > 7.0  log CFU/ml, with 0, 125, 250, 500, or 1,000 ppm of PRPA,
      respectively, and D(56.7 degrees C)-values were 2.99, 1.05, 0.68, 0.26 and <=0.16
      min. Albumen (pH 8.9) pasteurized under FSIS standards incurred salmonellae
      reductions of 3.3, 2.8, 5.2, > 7.0, and > 7.0 log CFU/ml,  with 0, 125, 250, 500,
      or 1,000 ppm of PRPA, respectively, while D(56.7 degrees C)-values were 0.87,
      0.99, 0.66, 0.22, and 0.09 min. Adding 500 ppm of PRPA to albumen (pH 7.8)
      reduced D(56.7 degrees C)-values more than 11-fold, and reduced the time to
      achieve a 5-log  reduction from 15.0 to only 1.3 min. A 7-log reduction in plain
      LEW (pH 7.8) at 56.7 degrees C required 20.9 min, versus only 1.8 and 1.1 min
      with 500 and 1,000 ppm of PRPA, respectively. Furthermore, a 7-log reduction in
      plain LEW (pH 8.9) required 6.1 min, versus only 1.5 and 0.6 min with 500  and
      1,000 ppm of PRPA, respectively. This study is the first to report the efficacy
      of PRPA (pK(a) = 8.4) in sensitizing Salmonella in LEW to thermal pasteurization,
      while documenting that PRPA retains its antibacterial efficacy at pH levels as
      high as 8.9.

PMID- 22410217
TI  - Analysis of the relationship between economic measures and Salmonella testing
      results in young chicken slaughter establishments.
AB  - Food processing establishments incur costs to install, maintain, and operate
      equipment and implement specific food safety practices. During times of economic
      recession, establishments might reduce their food safety efforts to conserve
      resources and reduce costs of operation. This study  was conducted to determine
      whether financial performance measures are systematically associated with
      Salmonella test results. The association between Salmonella test results from 182
      federally inspected young chicken slaughter establishments from 2007 to 2009 and
      financial performance  was examined while controlling for other establishment
      characteristics. Results indicated that the smallest establishments, which
      slaughtered fewer than 0.2 million chickens per year, had three times as many
      positive test results as did the largest establishments, which slaughtered more
      than  86.0 million chickens per year (P < 0.01). Establishments that slaughtered
      more than 0.2 million but fewer than 18.5 million chickens had 1.5 times as many
      positive test results (P = 0.02). Two statistically significant financial
      performance measures were identified, but the  effects were limited.
      Establishments in bankruptcy had 1.4 times as many positive test results as did
      those not in bankruptcy (P = 0.02); however, only five establishments were in
      bankruptcy. Establishments with better payment performance generally had better
      Salmonella test  results, but the effect was significant only in the winter
      season.

PMID- 22410218
TI  - Survival and growth of epidemically successful and nonsuccessful Salmonella
      enterica clones after freezing and dehydration.
AB  - The spread of epidemically successful nontyphoidal Salmonella clones has been
      suggested as the most important cause of salmonellosis in industrialized
      countries. Factors leading to the emergence of success clones are largely
      unknown, but their ability to survive and grow after  physical stress may
      contribute. During epidemiological studies, a mathematical model was developed
      that allowed estimation of a factor (q) accounting for the relative ability of
      Salmonella serovars with different antimicrobial resistances to survive in the
      food chain and cause  human disease. Based on this q-factor, 26 Salmonella
      isolates were characterized as successful or nonsuccessful. We studied the
      survival and growth of stationary- and exponential-phase cells of these isolates
      after freezing for up to 336 days in minced meat. We also investigated  survival
      and growth after dehydration at 10 degrees C and 82% relative humidity (RH) and
      25 degrees C and 49% RH for 112 days. Stationary-phase cells were reduced by less
      than 1 log unit during 1 year of freezing, and growth was initiated with an
      average lag phase of 1.7 h. Survival was lower in exponentialphase  cells, but
      lag phases tended to be shorter. High humidity and low temperature were less
      harmful to Salmonella than were low humidity and high temperature. Tolerance to
      adverse conditions was highest for Salmonella Infantis and one Salmonella
      Typhimurium U292 isolate and  lowest for Salmonella Derby and one Salmonella
      Typhimurium DT170 isolate. Dehydration, in contrast to freezing, was differently
      tolerated by the Salmonella strains in this study, but tolerance to freezing and
      dehydration does not appear to contribute to the emergence of  successful
      Salmonella clones.

PMID- 22410219
TI  - Survival of Salmonella in home-style mayonnaise and acid solutions as affected by
      acidulant type and preservatives.
AB  - Mayonnaise made from contaminated eggs has been linked to outbreaks of Salmonella
      infections. This study was undertaken to determine the fate of salmonellae in
      home-style mayonnaise and acid solutions with or without chemical preservatives.
      Egg yolks were inoculated with different  levels of a three-serotype
      (Typhimurium, Heidelberg, and Enteritidis [untypeable phage type]) mixture of
      Salmonella or a three-phage-type (4, 8, and 13) mixture of Salmonella
      Enteritidis. The inoculated yolks were used to make mayonnaise with 2, 3, or 4
      teaspoons of a commercial  wine vinegar or lemon juice. The mayonnaise was
      sampled for salmonellae over a 15-day period at 4 degrees C, and negative samples
      were tested further by a three-tube most-probable-number assay. The same
      Salmonella mixtures were respectively inoculated into six acid solutions
      including wine  vinegar, lemon juice, and acetic or citric solutions with or
      without chemical preservatives. The Salmonella populations of the Salmonella
      Enteritidis mixture were more persistent than those of the other Salmonella
      mixture in mayonnaise. Both Salmonella mixtures  survived longer in mayonnaise
      made with vinegar than with lemon juice during storage at 4 degrees C. In the
      acid solutions, however, the populations of the two  Salmonella mixtures were not
      significantly different. The numbers of the two Salmonella mixtures in acetic or
      citric acid  solutions with the preservatives were significantly lower than those
      in vinegar, lemon juice, and the solutions without the preservatives. Results
      suggest that Salmonella in contaminated egg yolks could survive the mayonnaise
      making process. The inhibition of Salmonella by vinegar  and lemon juice is due
      to the hurdle effect of organic acids and chemical preservatives.

PMID- 22410220
TI  - Dispersal of Salmonella Typhimurium by rain splash onto tomato plants.
AB  - Outbreaks of Salmonella enterica have increasingly been associated with tomatoes
      and traced back to production areas, but the spread of Salmonella from a point
      source onto plants has not been described. Splash dispersal by rain could be one
      means of dissemination. Green fluorescent protein-labeled, kanamycin-resistant
      Salmonella enterica sv. Typhimurium dispensed on the surface of plastic mulch,
      organic mulch, or soil at 108 CFU/cm2 was used as the point source in the center
      of a rain simulator. Tomato plants in soil with and without plastic or organic
      mulch were placed around the point source, and rain intensities of 60 and 110
      mm/h were applied for 5, 10, 20, and 30 min. Dispersal of Salmonella followed a
      negative exponential model with a half distance of 3 cm at 110 mm/h. Dispersed
      Salmonella survived for 3 days on tomato leaflets, with a total decline of 5 log
      and an initial decimal reduction time of 10 h. Recovery of dispersed Salmonella
      from plants at the maximum observed distance ranged from 3 CFU/g of leaflet after
      a rain episode of 110 mm/h for 10 min on soil to 117 CFU/g of leaflet on plastic
      mulch. Dispersal of Salmonella on plants with and without mulch was significantly
      enhanced by increasing rain duration from 0 to 10 min, but dispersal was reduced
      when rainfall duration increased from 10 to 30 min. Salmonella may be dispersed
      by rain to contaminate tomato plants in the field, especially during rain events
      of 10 min and when plastic mulch is used.

PMID- 22410221
TI  - Comparative examination of Escherichia coli O157:H7 survival on romaine lettuce
      and in soil at two independent experimental sites.
AB  - Little is known about the influence of abiotic factors such as climate and soil
      chemistry on the survival of Escherichia coli O157:H7 in field lettuce. We
      applied a nalidixic acid-resistant derivative of strain ATCC 700728 to field
      grown romaine lettuce in two regions in Canada characterized by large variances
      in soil type and climate. Surviving populations in soil and on lettuce leaves
      were estimated on sorbitol MacConkey agar supplemented with nalidixic acid. Data
      were fitted with the Weibull decline function to permit comparison of decay rates
      in the two experimental sites. E. coli O157:H7 populations fell from 105 to <102
      CFU/g on leaves, and <103 CFU/g in soil within 7 days after inoculation. Analysis
      revealed there was no significant difference between decay rates at the two
      experimental sites in either environment. The results of this study suggest that
      the inherent ecological fitness of E. coli O157:H7 ATCC 700728 determines the
      extent of survival in the production environment.

PMID- 22410224
TI  - Monitoring transmission routes of Listeria spp. in smoked salmon production with
      repetitive element sequence-based PCR techniques.
AB  - Various techniques have been used for tracing the transmission routes of Listeria
      species and for the assessment of hygiene standards in food processing plants.
      The potential of repetitive element sequence-based PCR (Rep-PCR) methods (GTG5
      and REPI + II) for the typing of Listeria isolates (n = 116), including Listeria
      monocytogenes (n = 46), was evaluated in a particular situation arising from the
      relocation of a company producing cold-smoked salmon. Pulsed-field gel
      electrophoresis (PFGE) using three restriction enzymes (ApaI, AscI, and SmaI) was
      used for comparison. Identical transmission scenarios among two companies could
      be identified by cluster analysis of L. monocytogenes isolates that were
      indistinguishable by both Rep-PCR and PFGE. The calculated diversity index (DI)
      indicates that Rep-PCR subtyping of Listeria species with primer sets GTG5 and
      REPI + II has a lower discrimination power than does PFGE. When concatenated Rep
      PCR cluster analysis was used, the DI increased from 0.934 (REPI + II) and 0.923
      (GTG5) to 0.956. The discrimination power of this method was similar to that of
      PFGE typing based on restriction enzyme Apa I (DI = 0.955). Listeria welshimeri
      may be useful as an indicator for monitoring smoked salmon processing
      environments. Rep-PCR meets the expectations of a reasonable, fast, and low-cost
      molecular subtyping method for the routine monitoring of Listeria species. The
      discriminatory power as characterized by the DI sufficiently quantifies the
      probability of unrelated isolates being characterized as different subtypes.
      Therefore, Rep-PCR typing based on two primer systems (GTG5 and REPI + II) may be
      a useful tool for monitoring industrial hygiene.

PMID- 22410222
TI  - Essential oils reduce Escherichia coli O157:H7 and Salmonella on spinach leaves.
AB  - The efficacy of cinnamaldehyde and Sporan for reducing Escherichia coli O157:H7
      and Salmonella on spinach leaves was investigated. Spinach leaves were inoculated
      with a five-strain cocktail of Salmonella or E. coli O157:H7, air dried for ca.
      30 min, and then  immersed in a treatment solution containing 5 ppm of free
      chlorine, cinnamaldehyde, or Sporan (800 and 1,000 ppm) alone or in combination
      with 200 ppm of acetic acid (20%) for 1 min or with water (control). After spin
      drying, treated leaves were analyzed periodically during 14 days of storage  at 4
      degrees C for Salmonella, E. coli O157:H7, total coliforms, mesophilic and
      psychrotrophic bacteria, and yeasts and molds. Treatment effects on color and
      texture of leaves also were determined. Sporan alone (1,000S), Sporan plus acetic
      acid (1,000SV), and cinnamaldehyde-Tween (800T)  reduced E. coli O157:H7 by more
      than 3 log CFU/g (P < 0.05), and 1,000SV treatment reduced Salmonella by 2.5 log
      CFU/g on day 0. E. coli O157:H7 and Salmonella populations on treated spinach
      leaves declined during storage at 4 degrees C. The 1,000SV treatment  was
      superior to chlorine and other treatments for reducing E. coli O157:H7 during
      storage. Saprophytic microbiota on spinach leaves increased during storage at 4
      degrees C but remained lower on leaves treated with Sporan (800S) and Sporan plus
      acetic acid (1,000SV) than on control leaves.  The color and texture of Sporan
      treated leaves were not significantly different from those of the control leaves
      after 14 days. Sporan plus acetic acid (1,000SV) reduced E. coli O157:H7 and
      Salmonella on baby spinach leaves without adverse effects on leaf color and
      texture.

PMID- 22410227
TI  - Molecular characterization of spoilage bacteria as a means to observe the
      microbiological quality of carrot.
AB  - This study characterized the bacteria causing decay of carrots during storage and
      marketing. Spoilage strains were identified by 16S-amplified rDNA restriction
      analysis and intergenic transcribed spacer-PCR-restriction fragment length
      polymorphism (ITS-PCR-RFLP). Genotypic  fingerprinting by RFLP-pulsed-field gel
      electrophoresis was used to assess the genetic diversity of the isolates. A total
      of 252 Pseudomonas isolates from carrots were identified and classified into
      eight separate groups. Most strains belonged to group A (Pseudomonas fluorescens,
      Pseudomonas marginalis, and Pseudomonas veronii) and group B (Pseudomonas
      putida). The strains identified as Pectobacterium carotovorum subsp. carotovorum,
      Pectobacterium atrosepticum, Dickeya chrysanthemi, and Erwinia rhapontici were
      distinguished by  ITS-PCR-RFLP. All isolates belonging to the genera
      Pectobacterium and Erwinia were responsible for carrot spoilage. This work has
      led to the development of new strategies for the identification and genotyping of
      vegetable-spoiling strains of Pseudomonas, Pectobacterium,  and Erwinia. This is
      also the first report describing the occurrence of carrot-spoiling E. rhapontici.
      Early recognition of spoilage bacteria in vegetables is important for the
      implementation of effective handling strategies. Pectolytic bacteria may cause
      considerable financial  losses because they account for a large proportion of
      bacterial rot of fruits and vegetables during storage, transit, and marketing.

PMID- 22410223
TI  - High pressure inactivation of Escherichia coli, Campylobacter jejuni, and
      spoilage microbiota on poultry meat.
AB  - This study evaluated the high pressure inactivation of Campylobacter jejuni,
      Escherichia coli, and poultry meat spoilage organisms. All treatments were
      performed in aseptically prepared minced poultry meat. Treatment of 19 strains of
      C. jejuni at 300 MPa and 30 degrees C revealed  a large variation of pressure
      resistance. The recovery of pressure-induced sublethally injured C. jejuni
      depended on the availability of iron. The addition of iron content to enumeration
      media was required for resuscitation of sublethally injured cells. Survival of C.
      jejuni  during storage of refrigerated poultry meat was analyzed in fresh and
      pressuretreated poultry meat, and in the presence or absence of spoilage
      microbiota. The presence of spoilage microbiota did not significantly influence
      the survival of C. jejuni. Pressure treatment at 400 MPa and  40 degrees C
      reduced cell counts of Brochothrix thermosphacta, Carnobacterium divergens, C.
      jejuni, and Pseudomonas fluorescens to levels below the detection limit. Cell
      counts of E. coli AW1.7, however, were reduced by only 3.5 log (CFU/g) and
      remained stable during subsequent  refrigerated storage. The resistance to
      treatment at 600 MPa and 40 degrees C of E. coli AW1.7 was compared with
      Salmonella enterica, Shiga toxin-producing E. coli and nonpathogenic E. coli
      strains, and Staphylococcus spp. Cell counts of all organisms except  E. coli AW
      1.7 were reduced by more than 6 log CFU/g. Cell counts of E. coli AW1.7 were
      reduced by 4.5 log CFU/g only. Moreover, the ability of E. coli AW1.7 to resist
      pressure was comparable to the pressure-resistant mutant E. coli LMM1030. Our
      results indicate  that preservation of fresh meat requires a combination of high
      pressure with high temperature (40 to 60 degrees C) or other antimicrobial
      hurdles.

PMID- 22410225
TI  - Critical issues in detecting viable Listeria monocytogenes cells by real-time
      reverse transcriptase PCR.
AB  - Rapid and specific detection of viable Listeria monocytogenes cells, particularly
      in processed foods, is a major challenge in the food industry. To assess the
      suitability of using RNA-based detection methods to detect viable cells, several
      sets of PCR primers and florescent probes  were designed targeting the 16S rRNA,
      internalin A, and ribosomal protein L4 genes. One-step real-time reverse
      transcriptase (RT) PCR assays were conducted using RNAs extracted from control
      and heat-treated L. monocytogenes samples. The cycle threshold values were
      significantly higher  in heat-treated cells than in controls. However, real-time
      RT-PCR amplification signals were still detected even in samples stored at room
      temperature for 24 h after lethal treatments, and the intensity of the signals
      was correlated with the cell population. The 16S rRNA molecules were the  most
      stable of the three targets evaluated, and the impact on detection efficacy of
      the relative positions of the PCR primers within the target genes was limited
      under the experimental conditions. These results suggest that real-time RT-PCR
      assays have advantages over conventional PCR assays  for assessing viable L.
      monocytogenes cells, but the results are affected by the stability of the RNA
      molecules targeted. These findings could have a major impact on interpretation of
      RNA-based detection data and gene expression studies.

PMID- 22410228
TI  - Effect of temperature, pH, and NaCl on the inactivation kinetics of murine
      norovirus.
AB  - We investigated the resistance of murine norovirus (MNV) and coliphage MS2, a
      culturable human norovirus surrogate, to temperature, salt, and pH. Virus
      inactivation was measured by plaque, real-time TaqMan reverse transcription (RT)
      PCR, and long-template RT-PCR assays. Both MNV and MS2 were rapidly inactivated
      at temperatures above 60 degrees C. Similarly, MNV tolerated low salt
      concentrations (0.3% NaCl) to a greater degree than high salt concentrations (3.3
      to 6.3% NaCl). MNV was relatively resistant to strong acidic conditions (pH 2)
      and was more tolerant of slightly acidic (pH 4) or neutral (pH 7) conditions. In
      contrast, MS2 was resistant to high salinity. Overall, temperature had a greater
      effect on infectivity than salt or low pH. Additionally, temperature and low pH
      had a synergistic effect on MNV infectivity. Both real-time and long-template RT
      PCR assays significantly underestimated the inactivation by temperature, salt,
      and pH. The inactivation kinetics of both MNV and MS2 under various environmental
      conditions gave a good fit by the Weibull model (R2 > 0.9). This study suggests
      both the capacity of infectious human norovirus to persist in the face of various
      environmental conditions and its sensitivity to high temperatures, which may
      provide a mechanism of protection against this virus.

PMID- 22410226
TI  - Molecular and toxigenic characterization of Bacillus cereus and Bacillus
      thuringiensis strains isolated from commercial ground roasted coffee.
AB  - Thirty samples of roasted ground coffee beans from 10 different commercial brands
      were analyzed to investigate the occurrence and levels of Bacillus cereus and
      Bacillus thuringiensis strains. Strains were evaluated for their genetic
      diversity by repetitive element sequence  polymorphism PCR (Rep-PCR) and for
      their toxigenic profiles, i.e., the presence of hblA, hblC, hblD, nheA, nheB,
      nheC, cytK, ces, and entFM. Survival and multiplication of B. cereus sensu lato
      in the ready-to-drink coffee was determined to evaluate this beverage as a
      possible  vehicle for B. cereus infection. B. cereus was detected in 17 (56.7%)
      of the 30 samples, and B. thuringiensis was detected in 8 (26.7%) of the 30
      samples. Five samples did not produce any characteristic growth. The most common
      gene, entFM, was detected in 23 strains  (92%). The NHE complex (nheA, nheB, and
      nheC genes) was found in 19 strains (76%). The HBL complex (hblA, hblC, and hblD)
      was found in 16 strains (64%). All strains were negative for ces. The cytK gene
      was found in 16 strains (64%). The  computer-assisted cluster analysis of Rep-PCR
      profiles using a clustering criterion of 80% similarity revealed four main
      clusters. Cluster 1 was the predominant and comprised three B. thuringiensis
      strains with 100% similarity, cluster 2 comprised two B. cereus strains (100% 
      similarity), cluster 3 comprised two B. thuringiensis strains (90% similarity),
      and cluster 4 comprised one B. thuringiensis strain and one B. cereus strain (85%
      similarity). The cluster analysis of fingerprints generated by Rep-PCR revealed a
      high genetic diversity among  the B. cereus strains, suggesting that the
      contamination could have originated from different sources. In our experiments,
      when sugar was added and the beverage was kept in thermic bottles there was a
      significant increase in B. cereus sensu lato levels, which may increase the  risk
      of food poisoning. These results highlight the need for additional studies on
      this subject to better evaluate coffee as a food poisoning vehicle.

PMID- 22410229
TI  - Assessment of the efficacy of benzalkonium chloride and sodium hypochlorite
      against Acanthamoeba polyphaga and Tetrahymena spp.
AB  - The efficacy of benzalkonium chloride and sodium hypochlorite against
      Acanthamoeba polyphaga and two Tetrahymena spp. was determined based on the
      European Standard EN 1276:2009 suspension test. Trophozoite viability was
      assessed by determination of the membrane integrity  using flow cytometry as a
      fast screening technique. Bovine serum albumin was added to simulate clean (0.3
      g/liter) and dirty (3 g/liter) conditions. Benzalkonium chloride caused cell
      lysis at concentrations above 50 mg/liter under clean and dirty conditions. A
      concentration of 50 mg of free  chlorine per liter had a strong biocidal effect
      on acanthamoebae and tetrahymenae after 15 min under clean and dirty conditions.
      Our results suggest that benzalkonium chloride and sodium hypochlorite were
      effective against the three microorganisms at concentrations commonly applied in
      the  food industry.

PMID- 22410230
TI  - Bioefficacy of essential and vegetable oils of Zanthoxylum xanthoxyloides seeds
      against Acanthoscelides obtectus (Say) (Coleoptera: Bruchidae).
AB  - Experiments were conducted in the laboratory to evaluate the bioefficacy of
      essential and vegetable oils of Zanthoxylum xanthoxyloides (Rutaceae) against
      Acanthoscelides obtectus (Coleoptera: Bruchidae). The chemical composition of the
      essential oil and the fatty acid composition of the vegetable oil extracted from
      the seeds of Z. xanthoxyloides were determined. The insecticidal activities of
      these oils and the associated aromatized clay powder were evaluated against A.
      obtectus. Both oils were strongly repellent (100% repellency at 0.501 MUl/cm2
      essential oil and 3.144 MUl/cm2 vegetable oil) and highly toxic (LC50 = 0.118
      MUl/cm2 for essential oil) to this beetle after contact on filter paper. The
      vapors of the essential oil were highly toxic to adult insects (LC50 = 0.044
      MUl/cm3), and the aromatized powder made from clay and essential oil was more
      toxic (LD50 = 0.137 MUl/g) than the essential oil alone (LD50 = 0.193 MUl/g)
      after 2 days of exposure on a common bean. Both oils greatly reduced the F1
      insect production and bean weight loss and did not adversely affect the bean seed
      viability. In general, the results obtained indicate that these plant oils can be
      used for control of A. obtectus in stored beans.

PMID- 22410231
TI  - Trends in ownership and usage of food thermometers in the United States, 1998
      through 2010.
AB  - Food safety research has shown that the use of a food thermometer is the best way
      to ensure that meat, poultry, and other foods reach an internal temperature
      sufficient to destroy foodborne pathogens. The 1998, 2001, 2006, and 2010 Food
      Safety Surveys were used to analyze changes in  food thermometer ownership and
      usage for roasts, chicken parts, and hamburgers in the United States. A probit
      regression model was used to evaluate differing trends in ownership across
      demographic subgroups, and probit models with sample selection were used to
      evaluate differing trends in  food thermometer usage for roasts, chicken parts,
      and hamburgers. The Food Safety Surveys are nationally representative telephone
      surveys tracking consumers' food safety attitudes and behaviors. Findings from
      these surveys indicate that the percentage of consumers who own food thermometers
      has increased from 49% in 1998 to 70% in 2010 (P < 0.05). The use of food
      thermometers has also increased over this time period but varies by food type. Of
      those who own food thermometers, a higher percentage reported using thermometers
      for roasts (76% in 1998 and 82% in 2010, P  < 0.05) than for chicken parts (33%
      in 1998 and 53% in 2010, P < 0.05) and hamburgers (14% in 1998 and 23% in 2010, P
      < 0.05). The results also show that men, non-Hispanic whites, those with some
      college education or higher, those with higher incomes, and those 65 years  and
      older were more likely to own food thermometers. After controlling for food
      thermometer ownership, those aged 18 to 29 years were more likely to use a food
      thermometer for roasts and chicken parts than those aged 65 to 101 years. The
      results suggest that educational programs encouraging  food thermometer usage
      should focus first on food thermometer ownership.

PMID- 22410232
TI  - Sanitation and design of lettuce coring knives for minimizing Escherichia coli
      O157:H7 contamination.
AB  - This study was undertaken to examine the effect of ultrasound in combination with
      chlorine on the reduction of Escherichia coli O157:H7 populations on lettuce
      coring knives. Two new coring devices designed to mitigate pathogen attachment
      were fabricated and evaluated. The coring rings of the knives were dip inoculated
      with soil slurry containing 106 E. coli cells and treated with chlorinated water
      with and without ultrasonication for 30, 60, and 120 s. The rough welding joints
      on currently used in-field lettuce coring knives provided a site conducive to
      bacterial attachment and resistant to cell removal during sanitation treatment.
      The two modified coring knives harbored significantly fewer E. coli cells than
      did the currently used commercial model, and the efficacy of the disinfection
      treatment was high (P < 0.05). Ultrasound treatment reduced the E. coli O157:H7
      counts to below the detection limit of 1.10 log CFU/cm2 at both the coring ring
      blade and welding joint within 30 s in 1 ppm of chlorinated water. The redesigned
      coring knives and an ultrasound plus chlorine combination treatment may provide
      practical options for minimizing the microbial safety hazards of lettuce
      processed by core-in-field operations.

PMID- 22410233
TI  - Lack of effect of feeding citrus by-products in reducing salmonella in
      experimentally infected weanling pigs.
AB  - The objective of the current research was to determine if feeding the citrus by
      products(D) -limonene (DL) and citrus molasses would reduce the concentration and
      prevalence of Salmonella in weanling pigs experimentally infected with Salmonella
      Typhimurium. Twenty  crossbred weanling pigs (average body weight [BW], 19.9 kg)
      were randomly assigned to one of four treatments: control, low-dose DL (1.5 ml/kg
      of BW per day), high-dose DL (3.0 ml/kg of BW per day), and citrus molasses (0.05
      kg/kg of BW per day). Treatments were administered in the feed (twice  daily) for
      7 days, with one-half of the dose administered at each feeding. Fecal samples
      were collected twice daily (prior to administration of treatment) and cultured
      for quantitative and qualitative determination of the challenge strain of
      Salmonella. Upon termination of the study,  pigs were euthanized and tissues from
      the stomach, ileum, cecum, spiral colon, and rectum, as well as luminal contents,
      were collected. In addition, the popliteal and ileocecal lymph nodes and liver,
      spleen, and tonsil tissue were collected for qualitative Salmonella culture. No
      significant  treatment differences (P > 0.05) were observed among treatments for
      fecal concentration or prevalence of Salmonella throughout the 7-day collection
      period. Likewise, no treatment differences (P > 0.05) were observed for any of
      the tissue or luminal content samples  collected. Salmonella was not cultured
      from the muscle-bound popliteal lymph node but was cultured from the mesenteric
      ileocecal lymph nodes. While there were no effects in the current experiment,
      future research may examine the effect of a lower challenge dose and/or different
      administration  (dose or duration) of the citrus by-products.

PMID- 22410234
TI  - Survival of Campylobacter jejuni and Salmonella enterica Typhimurium in vacuum
      packed, moisture-enhanced pork.
AB  - The abilities of Campylobacter jejuni and Salmonella enterica Typhimurium to
      survive in vacuum-packaged, moisture-enhanced pork stored at 4 or 10 degrees C
      were examined. Pork loins were surface inoculated with either C. jejuni or
      Salmonella Typhimurium and then  moisture enhanced to a target of 10 or 20%. The
      enhanced pork loins were sliced 1 cm thick and vacuum packaged. A pork loin
      without moisture enhancement was sliced and vacuum packaged as a control. Samples
      were collected, plated, and the numbers of surviving organisms were determined
      periodically  during storage at 4 and 10 degrees C. The numbers of C. jejuni or
      Salmonella Typhimurium in samples with different moisture enhancement levels were
      similar (P > 0.05). No significant differences (P > 0.05) in C. jejuni counts
      were observed between samples  at 10 degrees C and those at 4 degrees C. In
      contrast, the numbers of Salmonella Typhimurium in samples at 10 degrees C had
      significantly (P < 0.05) increased (0.41 log CFU/g) from those at the
      refrigerated temperature of 4 degrees C. Vacuum storage at 4 and 10 degrees C for
      28 days did not result  in dramatic reductions in the mean numbers of C. jejuni
      and Salmonella Typhimurium. Our findings indicate that vacuum packaging under
      chilled conditions will not add substantially to safety for moisture-enhanced
      pork. Strict hygienic practices or the implementation of decontamination 
      technologies is recommended.

PMID- 22410235
TI  - Comparison of swab transport media for recovery of Listeria monocytogenes from
      environmental samples.
AB  - Environmental monitoring is recognized as an important strategy for controlling
      Listeria monocytogenes in food processing facilities. Samples are taken by
      swabbing environmental surfaces, and the swabs are immersed in a medium for
      transport to the laboratory. In this study, buffered  peptone water (BPW), Dey
      Engley neutralizing broth (DE), neutralizing buffer (NB), Letheen broth (LE), and
      newly described MCC buffer (MCC) were evaluated as transport media for recovery
      of sanitizer-stressed L. monocytogenes from inoculated swabs. After storage at 4
      degrees C, the media  performed similarly, but at 25 degrees C relative recovery
      efficiency from the inoculated sponges was DE > LE > BPW > MCC > NB. Recoveries
      from stainless steel surfaces followed similar trends. MCC, DE, and NB were
      compared for L. monocytogenes recovery in the presence of Escherichia  coli,
      Enterococcus faecalis, Lactobacillus plantarum, Pseudomonas fluorescens, and
      Listeria innocua. After 4 degrees C storage, all population levels changed
      little; after 25 degrees C storage, DE allowed the best growth of L.
      monocytogenes regardless of other species present. MCC,  DE, and NB performed
      similarly for recovery of L. monocytogenes from an artificial milk biofilm and
      for recovery of Listeria spp. from swabs obtained from a meat processing
      facility. Transport medium formulation, time and temperature of swab storage, and
      coexistence of other  species affect recovery of sanitizer-stressed L.
      monocytogenes from environmental swabs. The study confirms the need to maintain 4
      degrees C storage conditions during swab transport.

PMID- 22410236
TI  - Ability of inactivated yeast powder to adsorb patulin from apple juice.
AB  - This study aimed to investigate the adsorption of patulin from apple juice, using
      two types of inactivated yeast powder: laboratory-prepared yeast powder (LYP) and
      commercial yeast powder (CYP). The effects of incubation time, pH, incubation
      temperature, adsorbent amount, and initial  concentration of patulin and the
      stability of the yeast-mycotoxin complex were assessed. The results showed that
      the efficiencies of the two yeast types in adsorbing patulin were similar. The
      ability of the powders to remove patulin increased with longer incubation times,
      and patulin concentration  was below detectable levels with LYP and CYP at
      approximately 36 and 30 h, respectively. The highest removal of patulin was
      achieved at pH 5.0 for both powder types, and there were no significant
      differences in patulin decrease at different temperatures (4, 29, and 37 degrees
      C). Additionally,  the adsorption percentage of patulin increased significantly
      with the increase of absorbent amount and decrease of initial concentration of
      patulin. Stability of the yeast-patulin complex was assessed, and patulin was
      more stable when washed in phosphate-buffered saline (pH 4.0) than in absolute 
      ethyl alcohol. These results suggest that inactivated yeast powder has potential
      as a novel and promising adsorbent to bind patulin effectively.

PMID- 22410237
TI  - Biogenic amines and ethyl carbamate in primitivo wine: survey of their
      concentrations in commercial products and relationship with the use of malolactic
      starter.
AB  - This research was conducted to determine the biogenic amine (BA) and ethyl
      carbamate (EC) concentrations in commercial Primitivo wine samples and the
      influence of the use of malolactic starter culture on concentrations of these
      potentially hazardous compounds in this wine. One hundred  sixty bottles of wine
      from eight producers in the Apulia region of southern Italy were purchased at
      retail and analyzed. The most common BAs were histamine, 2-phenylethylamine,
      tyramine, cadaverine, putrescine, spermine, and spermidine. Putrescine (derived
      from ornithine) was the most abundant  BA in all commercial Primitivo wines (5.41
      to 9.51 mg/liter), 2-phenylethylamine was detected in only two commercial wines
      (at less than 2.12 mg/liter), and histamine was found at concentrations of 1.49
      to 16.34 mg/liter. The concentration of EC in commercial Primitivo wine was 6.81
      to 15.62  ppb, which is not considered dangerous for human health. Malolactic
      fermentation (MLF) affected the concentrations of BAs and EC differently. For EC,
      no significant differences were detected between samples of wine produced by
      spontaneous fermentation and wine that was inoculated malolactic  starter. Mean
      EC concentrations were 12 and 14 ppb in two batches tested (always 18 ppb or
      less), regardless of whether the malolactic starter was added. Although present
      at trace levels in wine before the MLF, histamine accumulated during the MLF
      process, regardless of whether the malolactic  starter was added. However, the
      increase in histamine was higher in wines without the malolactic starter. The
      concentrations of putrescine and cadaverine increased after MLF, especially in
      the wine that spontaneously fermented. The use of a selected malolactic starter
      resulted in reductions  in BA concentrations in wine produced by this guided MLF
      compared with wine produced by spontaneous MLF.

PMID- 22410238
TI  - Toxoplasma gondii in commercially available pork meat and cured ham: a
      contribution to risk assessment for consumers.
AB  - Toxoplasmosis is an infection caused by Toxoplasma gondii, whose transmission has
      usually been attributed to ingestion of undercooked or raw meat. Dry-cured ham is
      a high-quality meat product of increasing economic relevance, and epidemiological
      studies point to cured meat products  as a risk factor for acquiring
      toxoplasmosis. With the aim of contributing to the risk assessment process, 50
      samples of fresh pork meat and commercial cured ham were collected in the city of
      Zaragoza (northeastern Spain), and the presence of viable forms of T. gondii was
      analyzed.  A mouse concentration bioassay technique was used, and the presence of
      the parasite in mice was determined by indirect immunofluorescence assay. T.
      gondii was detected in two samples of rib, reflecting a frequency of 8% positive
      fresh pork meat (4% positivity of total samples analyzed).  Brains of
      seropositive mice were analyzed by histology and PCR, although the parasite was
      not isolated in the seroconverted mice. No viable forms were detected either in
      other types of fresh meat or in the samples of cured ham.

PMID- 22410239
TI  - Survival in vitro and virulence of Trypanosoma cruzi in acai pulp in experimental
      acute Chagas disease.
AB  - Chagas disease is a parasitic infection with high socioeconomic impact throughout
      Latin America. Although this severe, incurable disease can be transmitted by
      several routes, oral transmission is currently the most important route in the
      Amazon Basin. Acai pulp has nutritional properties and is popular throughout
      Brazil and abroad. However, this pulp has been associated with microepidemics of
      acute Chagas disease (ACD) in northern Brazil, where acai fruit is the main food
      supplement. In this study, we examined the in vitro survival and in vivo
      virulence of Trypanosoma cruzi Y strain in acai pulp. Aliquots of in natura acai
      pulp produced in Belem city in the northern Brazilian state of Para were mixed
      with 105 trypomastigotes. The samples were incubated at room temperature or at 4
      or -20 degrees C for various periods, and the parasites were isolated by forced
      sieving. The resulting eluates were examined by microscopy, and the
      trypomastigotes were administered intraperitoneally, orally, or by gavage to
      immunodeficient mice (C.B-17-Prkdc(scid)/PasUnib) that had been pretreated with
      antibiotics. Parasitemia was quantified by the Brener method, and mortality was
      recorded daily. All routes of administration resulted in ACD. A 5-day delay in
      the onset of parasitemia occurred with oral administration. The survival and
      virulence of the parasites were unaffected by prior incubation at room
      temperature for 24 h, at 4 degrees C for 144 h, and at -20 degrees C for 26 h.
      These results indicate that T. cruzi can survive and retain its virulence in acai
      pulp under various conditions and that cooling and freezing are not suitable
      methods for preventing foodborne ACD.

PMID- 22410240
TI  - Cronobacter spp. in powdered infant formula.
AB  - Cronobacter species are opportunistic pathogens, and a mortality rate of 40 to
      80% is associated with infections. This pathogen can cause a range of serious
      diseases such as meningitis, septicemia, necrotizing enterocolitis, and brain
      abscesses and has been responsible for a  variety of sequelae such as
      quadriplegia. Although Cronobacter can cause disease in both adults and infants,
      infant infections associated with powdered formula are the focus of this review.
      Since the first reported Cronobacter infection outbreak in 1958, powdered infant
      formula  has been identified as a major source of these outbreaks, resulting in
      many recalls of powdered infant formula worldwide. This contamination has created
      an immense problem for the powdered infant formula industry. In this review, we
      discuss the taxonomy of Cronobacter species, the natural  habitat of Cronobacter
      and its presence in foods, the physiology, pathogenicity, and virulence of
      Cronobacter species, and available detection methods. We also discuss reported
      cases of Cronobacter infection linked to powdered infant formula consumption and
      then focus  specifically on the official World Health Organization guidelines for
      preparation of powdered infant formula.

PMID- 22410241
TI  - Feasibility of a standardized ultrasound examination in patients with rheumatoid
      arthritis: a quality improvement among rheumatologists cohort.
AB  - BACKGROUND: Quality improvement is important to facilitate valid patient
      outcomes. Standardized examination procedures may improve the validity of US.The
      aim of this study was to investigate the learning progress for rheumatologists
      during training of US examination of the hand in patients with rheumatoid
      arthritis (RA). METHODS: Rheumatologists with varying degrees of experience in US
      were instructed by skilled tutors. The program consisted of two days with hands
      on training followed by personal US examinations performed in their individual
      clinics. Examinations were sent to the tutors for quality control. The US
      examinations were evaluated according to a scoring sheet containing 144 items. An
      acceptable examination was defined as > 80% correct scores. RESULTS: Thirteen
      rheumatologists participated in the study. They included a total of 104 patients
      with RA. Only few of the initial examinations were scored below 80%, and as
      experience increased, the scores improved (p = 0.0004). A few participants
      displayed decreasing scores.The mean time spent performing the standardized
      examination procedure decreased from 34 min to less than 10 minutes (p = 0.0001).
      CONCLUSION: With systematic hands-on training, a rheumatologist can achieve a
      high level of proficiency in the conduction of US examinations of the joints of
      the hand in patients with RA. With experience, examination time decreases, while
      the level of correctness is maintained. The results indicate that US may be
      applied as a valid measurement tool suitable for clinical practice and in both
      single- and multi-centre trials.

PMID- 22410242
TI  - Ozone visible symptoms and reduced root biomass in the subalpine species Pinus
      uncinata after two years of free-air ozone fumigation.
AB  - Concentrations of ozone often exceed the thresholds of forest protection in the
      Pyrenees, but the effect of ozone on Pinus uncinata, the dominant species in
      subalpine forests in this mountainous range, has not yet been studied. We
      conducted an experiment of free-air ozone fumigation with saplings of P. uncinata
      fumigated with ambient O(3) (AOT40 May-Oct: 9.2 ppm h), 1.5 * O(3amb) (AOT40 May
      Oct: 19.2 ppm h), and 1.8 * O(3amb) (AOT40 May-Oct: 32.5 ppm h) during two
      growing seasons. We measured chlorophyll content and fluorescence, visible
      injury, gas exchange, and above- and below-ground biomass. Increased exposures to
      ozone led to a higher occurrence and intensity of visible injury from O(3) and a
      24-29% reduction of root biomass, which may render trees more susceptible to
      other stresses such as drought. P. uncinata is thus a species sensitive to O(3),
      concentrations of which in the Pyrenees are already likely affecting this
      species.

PMID- 22410243
TI  - Homeland security: IgA immunity at the frontiers of the body.
AB  - IgA is the most abundant immunoglobulin produced in mammals, and is mostly
      secreted across mucous membranes. At these frontiers, which are constantly
      assaulted by pathogenic and commensal microbes, IgA provides part of a layered
      system of immune protection. In this review, we describe how IgA induction occurs
      through both T-dependent and T-independent mechanisms, and how IgA is generated
      against the prodigious load of commensal microbes after mucosal dendritic cells
      (DCs) have sampled a tiny fraction of the microbial consortia in the intestinal
      lumen. To function in this hostile environment, IgA must be induced behind the
      'firewall' of the mesenteric lymph nodes to generate responses that integrate
      microbial stimuli, rather than the classical prime-boost effects characteristic
      of systemic immunity.

PMID- 22410244
TI  - Proteomic profiling of the substantia nigra demonstrates CNDP2 overexpression in
      Parkinson's disease.
AB  - Despite decades of intensive investigations, the precise sequence of molecular
      events and the specific proteins mediating the degenerative process underlying
      Parkinson's disease (PD) remain unraveled. Proteomic strategies may provide
      unbiased tools to identify novel candidates and explore original mechanisms
      involved in PD. Substantia nigra pars compacta (SN) tissue, whose degeneration is
      the hallmark of PD, was dissected from neuropathologically confirmed PD patients
      (n=3) and control subjects (n=3), before being submitted to a comparative 2-DE
      analysis. The present study revealed a subset of neuronal and/or glial proteins
      that appears to be deregulated in PD and likely to contribute to
      neurodegeneration. Observed alterations not only consolidate well accepted
      concepts surrounding PD pathogenesis such as oxidative stress and mitochondrial
      dysfunction but also point out to novel pathways. Among the latter, cytosolic non
      specific dipeptidase 2 (CNDP2), a relatively unknown protein not yet reported to
      be associated with PD pathogenesis, was shown to be increased in the SN of PD
      patients, as confirmed by Western blot. Immunohistochemical analyses demonstrated
      the presence of CNDP2 within the cytoplasm of SN dopaminergic neurons.
      Altogether, our findings support a key role of CNDP2 in PD neurodegeneration, by
      mechanisms that could involve oxidative stress, protein aggregation or
      inflammation. This article is part of a Special Issue entitled: Translational
      Proteomics.

PMID- 22410245
TI  - Long-term radiographic outcome of nodular bronchiectatic Mycobacterium avium
      complex pulmonary disease.
AB  - BACKGROUND: Although Mycobacterium avium complex pulmonary disease (MAC-PD) is a
      growing health problem, little is known about long-term radiographic outcome and
      factors for deterioration in patients with MAC-PD. METHODS: Data on patients with
      nodular bronchiectatic (NBE)  MAC-PD who underwent regular follow-up for >5 years
      were retrospectively reviewed. Changes in plain chest radiograph (CXR) and
      baseline characteristics were compared between the stable and deteriorated
      groups. RESULTS: Seventy-two patients were investigated, including 30 patients
      who  were examined 10 years after the initial visit. One patient (1.4%) showed
      progressive or remarkably progressive disease on CXR at 1 year; this rate
      increased to 22.2% at 5 years and to 53.3% at 10 years. Body mass index (BMI) at
      the initial visit was lower in the deteriorated group than in  the stable group.
      Cavitary disease and resistance to a macrolide were seen more frequently at the
      initial visit in the deteriorated group than in the stable group. CONCLUSIONS:
      NBE MAC-PD is a slowly but substantially progressive long-term infection (5-10
      years). Our data suggest  that patients with lower BMI, cavitary disease and
      resistance to a macrolide at initial visit are more likely to progress to
      deteriorating disease.

PMID- 22410246
TI  - INTERSEPT study: we still need more clarity.

PMID- 22410247
TI  - Aglycone-focused randomization of 2-difluoromethylphenyl-type sialoside suicide
      substrates for neuraminidases.
AB  - A selective and potent inhibitor of neuraminidases, a hydrolase that is
      responsible for processing sialylated glycoconjugates, is a promising drug
      candidate for various infective diseases. The current study demonstrates that the
      use of an aglycone-focused library of 2-difluoromethylphenyl alpha-sialosides is
      an effective technique to find potent and selective mechanism-based labeling
      reagents for neuraminidases. The focused library was constructed from a 4-azide-2
      difluoromethylphenyl sialoside (2) and an alkyne-terminated compound library by a
      click reaction. The focused library showed different inhibition patterns for two
      neuraminidases, Vibrio cholerae neuraminidase (VCNA) and human neuraminidase 2
      (hNeu2), and the most potent inhibitors for each neuraminidase were selected. A
      kinetic analysis of the selected inhibitors demonstrated that the modification of
      the aglycone moiety improved the K(I) value with little change in the t(1/2)
      value of the enzyme activity relative to the basic skeleton (2).

PMID- 22410248
TI  - Free radical scavenging and antiproliferative properties of Biginelli adducts.
AB  - A series of Biginelli adducts bearing different substituents at C-4 position were
      synthesized by using p-sulfonic acid calix[4]arene as a catalyst. The in vitro
      potential to scavenge reactive nitrogen/oxygen species (RNS and ROS) and the
      ability to inhibit cancer cells growth were then investigated. Four adducts were
      found to be potent scavengers of 2,2-diphenyl-1-picrylhydrazyl (RNS) and/or
      superoxide anion (ROS) radicals. The antiproliferative activity against cancer
      cells was disclosed for the first time for 16 monastrol analogs. The capacity of
      all compounds to inhibit cancer cells growth was dependent on the histological
      origin of cells, except for BA24, which was highly active against all cell lines.
      BA20 and BA33 were as potent as the reference drug doxorubicin against adriamycin
      resistant ovarian and prostate cancer cells, respectively. These results
      highlight some monastrol analogs as lead compounds for the design of new free
      radical scavengers and anticancer agents.

PMID- 22410249
TI  - Synthesis and biological evaluation of novel potent angiotensin II receptor
      antagonists with anti-hypertension effect.
AB  - A series of novel angiotensin II type 1 receptor antagonists were prepared.
      Radioligand binding assay suggested that compounds 1b and 1c could be recognized
      by the AT(1) receptor with an IC(50) value of 1.6 +/- 0.09 nM and 2.64 +/- 0.7
      nM, respectively. In vivo anti-hypertension experiments showed that compounds
      (1a, 1b, 1c, 1e) elicited a significant decrease in SBP and DBP of spontaneous
      hypertensive rats (SHRs). The antihypertensive effects maintained for 10 h, which
      indicated that these compounds had a favorable blood pressure-lowering effect.
      Acute toxicity testing suggested that the LD(50) value of compound 1b was 2316.8
      mg/kg which was lower than valsartan (LD(50)=307.50 mg/kg) but higher than
      losartan (LD(50)=2248 mg/kg). So they could be considered as novel anti
      hypertension candidates and deserved for further investigation.

PMID- 22410250
TI  - The glomerular basement membrane.
AB  - The kidney's glomerular filtration barrier consists of two cells-podocytes and
      endothelial cells-and the glomerular basement membrane (GBM), a specialized
      extracellular matrix that lies between them. Like all basement membranes, the GBM
      consists mainly of laminin, type IV collagen, nidogen, and heparan sulfate
      proteoglycan. However, the GBM is unusually thick and contains particular members
      of these general protein families, including laminin-521, collagen
      alpha3alpha4alpha5(IV), and agrin. Knockout studies in mice and genetic findings
      in humans show that the laminin and type IV collagen components are particularly
      important for GBM structure and function, as laminin or collagen IV gene
      mutations cause filtration defects and renal disease of varying severities,
      depending on the nature of the mutations. These studies suggest that the GBM
      plays a crucial role in establishing and maintaining the glomerular filtration
      barrier.

PMID- 22410252
TI  - [Knowledge of treatments in hospital patients: a necesary tool for safety in
      health care].
AB  - OBJECTIVE: To determine the quantity and quality of drug information that
      patients receive in hospital. METHOD: Cross-sectional study conducted in February
      2011, by designing and conducting a structured questionnaire on 60 patients: 30
      inpatients and 30 outpatients. Descriptive analysis of the results was performed
      including, number and level of knowledge of medication treatment versus the
      "real" one, globally analysed by age and route of administration. RESULTS: A
      total of 234 drugs were analysed in the inpatient group. It was considered that
      45/234 (19.2%;95% CI: 14-25) were known properly by patients. In outpatients,
      this rises to 29/42 (69.0%;95% CI: 53-82). One third (33.3%) of patients check
      the medication before it is administered or provided. Inpatients are more aware
      of orally administered drugs, they knew 28.6% vs 5.1% of parenteral treatments.
      Just under half (45.3%) of inpatients and 2.4% of outpatients completely unknown
      the medication. The average age of patients with no knowledge of their medication
      was 68.5 years (SD=10.1) and had 8.7 drugs prescribed (SD=3.0). A total of 53.3%
      of inpatients and 93.3% of outpatients, considered to have been properly
      informed. Most of patients (96.7%) were satisfied with the information received.
      CONCLUSIONS: The results show an opportunity for improvement in the information
      given to patients, particularly to inpatients. To inform them, would enable them
      to act as a filter to potential medication errors, and as a necessary part to
      improve the safety of care.

PMID- 22410251
TI  - Recent advances involving the renin-angiotensin system.
AB  - The renin-angiotensin system (RAS) exercises fundamental control over sodium and
      water handling in the kidney. Accordingly, dysregulation of the RAS leads to
      blood pressure elevation with ensuing renal and cardiovascular damage. Recent
      studies have revealed that the RAS hormonal cascade is more complex than
      initially posited with multiple enzymes, effector molecules, and receptors that
      coordinately regulate the effects of the RAS on the kidney and vasculature.
      Moreover, recently identified tissue-specific RAS components have pleomorphic
      effects independent of the circulating RAS that influence critical homeostatic
      mechanisms including the immune response and fetal development. Further
      characterization of the diverse interactions between the RAS and other signaling
      pathways within specific tissues should lead to novel treatments for renal and
      cardiovascular disease.

PMID- 22410253
TI  - Evaluation of cloned cells, animal model, and ATRA sensitivity of human
      testicular yolk sac tumor.
AB  - The testicular yolk sac tumor (TYST) is the most common neoplasm originated from
      germ cells differentiated abnormally, a major part of pediatric malignant
      testicular tumors. The present study aimed at developing and validating the in
      vitro and vivo models of TYST and evaluating the sensitivity of TYST to
      treatments, by cloning human TYST cells and investigating the histology, ultra
      structure, growth kinetics and expression of specific proteins of cloned cells.
      We found biological characteristics of cloned TYST cells were similar to the yolk
      sac tumor and differentiated from the columnar to glandular-like or goblet cells
      like cells. Chromosomes for tumor identification in each passage met nature of
      the primary tumor. TYST cells were more sensitive to all-trans-retinoic acid
      which had significantly inhibitory effects on cell proliferation. Cisplatin
      induced apoptosis of TYST cells through the activation of p53 expression and down
      regulation of Bcl- expression. Thus, we believe that cloned TYST cells and the
      animal model developed here are useful to understand the molecular mechanism of
      TYST cells and develop potential therapies for human TYST.

PMID- 22410254
TI  - Resistance to intravenous immunoglobulin (IVIG) in Kawasaki disease: no influence
      of different IVIG lot utilisation.

PMID- 22410255
TI  - Impact of Aspergillus fumigatus in allergic airway diseases.
AB  - For decades, fungi have been recognized as associated with asthma and other
      reactive airway diseases. In contrast to type I-mediated allergies caused by
      pollen, fungi cause a large number of allergic diseases such as allergic
      bronchopulmonary mycoses, rhinitis, allergic sinusitis and hypersensitivity
      pneumonitis. Amongst the fungi, Aspergillus fumigatus is the most prevalent cause
      of severe pulmonary allergic disease, including allergic bronchopulmonary
      aspergillosis (ABPA), known to be associated with chronic lung injury and
      deterioration in pulmonary function in people with chronic asthma and cystic
      fibrosis (CF). The goal of this review is to discuss new understandings of host
      pathogen interactions in the genesis of allergic airway diseases caused by A.
      fumigatus. Host and pathogen related factors that participate in triggering the
      inflammatory cycle leading to pulmonary exacerbations in ABPA are discussed.

PMID- 22410256
TI  - Obstetric management of moderate and late preterm labour.
AB  - Moderate and late preterm births account for the majority of preterm babies. The
      common perception that birth at 32-36 weeks' gestation carries few risks is now
      being challenged, as these babies have increased risk of neonatal mortality and
      morbidity. However, spontaneous labour at this gestation frequently has no
      specific, easily identifiable precursor, although preterm birth per se has a
      number of epidemiological and clinical associations. Prediction and prevention of
      preterm birth is currently largely aimed at identifying women at high risk such
      as those with previous preterm birth, and targeting intervention at this group.
      Both cervical length assessment and fibronectin testing permit some modification
      of the likelihood of preterm birth in this group. Progesterone treatment for the
      prevention of preterm birth is currently being researched widely, and appears a
      potentially promising strategy. Babies born at 32-36 weeks' gestation need
      careful monitoring in labour, with modification of intervention in labour due to
      their prematurity.

PMID- 22410257
TI  - Advanced glycation end products and neurodegenerative diseases: mechanisms and
      perspective.
AB  - The age-related neurodegenerative disorders such as Alzheimer's, Parkinson's, and
      Huntington's diseases are characterized by the abnormal accumulation or
      aggregation of proteins. Advanced glycation end products (AGEs) are proteins or
      lipids that become glycated after exposure to sugars. The formation of AGEs
      promotes the deposition of proteins due to the protease resistant crosslinking
      between the peptides and proteins. Several proteins implicated in
      neurodegenerative diseases such as amyloid beta, tau, alpha-synuclein, and prions
      are glycated and the extent of glycation is correlated with the pathologies of
      the patients. These data suggest that AGEs contribute to the development of
      neurodegenerative diseases. In this review we summarize recent advances on the
      investigation of the roles of AGEs in neurodegenerative diseases, with special
      focus on Alzheimer's and Parkinson's diseases. It is clear that AGEs modification
      triggers the abnormal deposition and accumulation of the modified proteins, which
      in turn sustain the local oxidative stress and inflammatory response, eventually
      leading to the pathological and clinical aspects of neurodegenerative diseases.
      Further characterization of the molecular mechanisms responsible for AGEs
      mediated neurotoxicity will provide important clues on the development of novel
      strategies for the prevention and treatment of neurodegenerative diseases.

PMID- 22410258
TI  - Serum GFAP levels in optic neuropathies.
AB  - BACKGROUND: Complement mediated autoimmunity against aquaporin-4 results in
      astrocytic damage in neuromyelitis optica (NMO). There is evidence for increased
      CSF glial fibrillary acidic protein (GFAP) and S100B levels in acute NMO. Here we
      tested whether the CSF finding also holds true for the diagnostic value of serum
      GFAP and S100B levels in NMO. METHODS: A multicentre study included 322 patients
      from London (n=160), Nijmegen (n=95), Pecs (n=44), and Lyon (n=24). Patients were
      classified into the following diagnostic categories: neurological control
      patients (n=45), MS optic neuritis (MSON, n=38), isolated optic neuritis (ION,
      n=11), relapsing isolated optic neuritis (RION, n=48), chronic relapsing isolated
      optic neuropathy (CRION, n=18), unclassified optic neuritis (UCON, n=39), NMO
      (n=77) and relapsing remitting multiple sclerosis (RRMS, n=47). Serum GFAP and
      S100B levels were quantified using ELISA. RESULTS: Median serum GFAP but not
      S100B levels were significantly higher (p<0.0001, general linear model) in
      patients with NMO (4.83 pg/mL) if compared to MSON (1.5 pg/mL, p=0.0001), UCON
      (1.92 pg/mL, p<0.01), ION (0.0 ng/mL, p<0.05), RION (1.3 pg/mL, p<0.0001) and
      CRION (2.2 pg/mL, p=0.01). Serum GFAP levels in the control cohort (3.6 pg/mL)
      were not significantly different to NMO. There was no relationship between serum
      GFAP levels and any other clinical or demographic parameter. Serum S100B
      concentrations correlated with the number of relapses in MSON (R=0.83, p=0.005).
      CONCLUSION: In contrast to the CSF, neither serum GFAP nor S100B levels were of
      major diagnostic value for the laboratory supported differential diagnosis
      between optic neuritis in the context of NMO and other optic neuropathies.

PMID- 22410259
TI  - Cultivation practices and manufacturing processes to produce Hoodia gordonii
      extract for weight management products.
AB  - Hoodia gordonii (Masson) Sweet ex Decne., is a succulent shrub, indigenous to the
      arid regions of southern Africa. Indigenous people have historically utilised
      certain species of Hoodia, including H. gordonii, as a source of food and water.
      Studies by the Council for Scientific and Industrial Research (CSIR, South
      Africa) identified that extracts of H. gordonii had appetite suppressant activity
      associated with specific steroid glycosides. A programme to develop weight
      management products based around this discovery was implemented in 1998. An
      agronomy programme was established which demonstrated that it was possible to
      cultivate this novel crop on a commercial scale (in excess of 70 ha). In
      parallel, a food grade manufacturing process was developed consisting of four
      main steps: harvesting of H. gordonii plant stems, comminution, drying under
      controlled conditions and extraction using food grade solvents. Appropriate
      Quality Control (QC) procedures were developed. The extraction process is capable
      of delivering a consistent composition despite natural variations in the
      composition of the dried H. gordonii. Specifications were developed for the
      resulting extract. The intended use of the standardised H. gordonii extract was
      as a functional food ingredient for weight management products. Other development
      studies on characterisation, toxicology and pharmacology are reported separately.

PMID- 22410260
TI  - Safety profile of Hoodia gordonii extract: mouse prenatal developmental toxicity
      study.
AB  - Hoodia gordonii extract (0, 5, 15 or 50mg/kg body weight/day, n=24 mice/group)
      was orally administered by gavage to female CD-1 mice from gestation days 5-17.
      On gestation day 18 the females were euthanized and examined. Treatment at
      50mg/kg/day caused a marked reduction in feed intake and body weight gain. Feed
      consumption was sporadically reduced at 15 mg/kg/day. At 50 or 15 mg/kg/day fetal
      weights, ossification of some bones and full and empty uterus weights were
      reduced. There were no clear maternal or fetal effects at 5mg/kg/day.
      Reproductive indices were unaffected at all doses and there were no treatment
      related malformations, anomalies or variations. The overall study no-observed
      adverse-effect level was set at 5mg/kg/day. In summary, at doses that reduced
      maternal feed consumption, H. gordonii extract delayed fetal development. The
      fetal effects seen could be consequent to reduced maternal feed consumption, the
      desired biological activity of the test item.

PMID- 22410261
TI  - Safety profile of Hoodia gordonii extract: rabbit prenatal developmental toxicity
      study.
AB  - Hoodia gordonii extract was orally administered by gavage to groups of 22 female
      New Zealand white rabbits from day 3-28 after mating at doses of 0 (control), 3,
      6 or 12 mg/kg bodyweight/day. These doses were reached by a dose escalation phase
      between days 3 and 7 after mating. As well as a vehicle control group, a control
      group pair-fed to the high dose was also included. On day 29 after mating the
      females were euthanized and examined. Treatment at 6 or 12 mg/kg/day was
      associated with a dose-related reduction in feed intake and bodyweight gain. Feed
      consumption and bodyweight gain was unaffected at 3mg/kg/day. In spite of marked
      maternal effects at 12 mg/kg/day, reproductive indices were unaffected at all
      doses and there were no effects on fetal or placental weights and no
      morphological changes in the fetuses. The no-observed-effect level (NOEL) for
      developmental effects was therefore 12 mg/kg/day, and the maternal NOEL was
      3mg/kg/day. At doses that caused marked maternal effects, H. gordonii extract did
      not affect embryonic or fetal development in a species that is considered
      predictive of developmental toxicity in man.

PMID- 22410262
TI  - Chemical characterisation of Hoodia gordonii extract.
AB  - The chemical composition of a solvent extract of Hoodia gordonii termed
      'H.gordonii extract' has been characterised by hyphenated chromatographic methods
      and traditional analytical techniques. The extract consists of a mixture of
      steroid glycosides, fatty acids, plant sterols and polar organic material. High
      performance liquid chromatography (HPLC) with ultra violet (UV) and mass
      spectrometric (MS) detection was used to quantify and confirm the identity of a
      number of steroid glycosides (73.7% w/w) present in the extract. Gas
      chromatography (GC) with MS and flame ionisation detection (FID) was applied to
      determine the fatty acid (3.12% w/w) sterol (0.39% w/w) and alcohol (0.03% w/w)
      content of a saponified sample of the extract. Polar organic material was
      quantified by gravimetric methodology using C(18) SPE separation and was
      determined to be a minimum of 3% w/w. Moisture content was measured by Karl
      Fischer coulometric titration (0.81% w/w). The protein content was investigated
      by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) with
      SYPRO Ruby staining and a negative result was determined with a limit of
      detection of <0.001%w/w of protein per band. The chemical composition of the
      extract remained stable for 19 months when stored in re-sealable plastic bags at
      ambient (21-24 degrees C) temperature and <60% relative humidity.

PMID- 22410263
TI  - The neural mechanisms of percept-memory comparison in visual working memory.
AB  - Researchers have revealed that comparing the perceptual input with the
      representations stored in visual working memory initiates a rapid attention
      shift, which is predominantly triggered by the relevant-feature change. The
      comprehension of the change contents further necessitates a follow-up comparison
      that contrasts all the object features regardless of the task relevancy. However,
      whether such a distinct stage exists and how the process is carried on need
      further verification. We explored this issue by investigating the underlying
      neural mechanisms of the percept-memory comparison. By recording EEG, we found
      that both the task-relevant and -irrelevant feature changes elicited
      significantly more negative anterior N2 waves (230-340ms) rooting in the anterior
      cingulate cortex (ACC), and meanwhile activated the frontal theta (5-8Hz, 250
      550ms). These results suggest that a distinct comparison stage does exist, which
      is supported by the anterior N2, ACC and frontal theta.

PMID- 22410264
TI  - Cerebral-cortical networking and activation increase as a function of cognitive
      motor task difficulty.
AB  - Excessive increases in task difficulty typically result in marked attenuation of
      cognitive-motor performance. The psychomotor efficiency hypothesis suggests that
      poor performance is mediated by non-essential neural activity and cerebral
      cortical networking (inefficient cortical dynamics). This phenomenon may underlie
      the inverse relationship between excessive task difficulty and performance.
      However, investigation of the psychomotor efficiency hypothesis as it relates to
      task difficulty has not been conducted. The present study used
      electroencephalography (EEG) to examine cerebral cortical dynamics while
      participants were challenged with both Easy and Hard conditions during a
      cognitive-motor task (Tetris((r))). In accord with the psychomotor efficiency
      hypothesis, it was predicted that with increases in task difficulty, participants
      would demonstrate greater 'neural effort,' as indexed by EEG spectral power and
      cortical networking (i.e., EEG coherence) between the premotor (motor planning)
      region and sensory, executive, and motor regions. Increases in neural activation
      and cortical networking were observed during the Hard condition relative to the
      Easy condition, thus supporting the psychomotor efficiency hypothesis. To further
      determine the unique contributions of cognitive versus sensory-motor demands, a
      control experiment was conducted in which cognitive demand was increased while
      sensory-motor demand was held constant. This experiment revealed that regionally
      specific neural activation was influenced by changes in cognitive demand, whereas
      cortical networking to the motor planning region was sensitive only to changes in
      sensory-motor demand. Crucially, the present study is the first, to our
      knowledge, to characterize the separate impact of cognitive versus sensory-motor
      demands on cerebral cortical dynamics. The findings further inform the dynamics
      of the cortical processes that underlie the quality of cognitive-motor
      performance particularly with regard to task difficulty. A broader understanding
      of the brain and muscle interactions during varying levels of challenge may
      inform the design of effective training protocols aimed at optimizing cognitive
      motor performance.

PMID- 22410265
TI  - Cardiac workload and inhibitory control in younger and older adults.
AB  - Our goal was to investigate age differences in the role played by cardiovascular
      regulation in response control. We questioned whether pre-test respiratory sinus
      arrhythmia (RSA; an index of phasic vagal cardiac control) and/or rate pressure
      product (RPP; a measure of cardiac workload) were associated with error rate
      and/or error-related electrocortical responses (ERPs) during a Go/NoGo inhibitory
      control task across three levels of working memory load. ERPs, RSA and RPP were
      indirectly associated with performance in young adults. Within the older group,
      higher resting RPP was directly associated with NoGo errors at all levels of
      load, an association not seen in the younger group. Thus, for older adults,
      excessive hemodynamic demands at rest were more relevant than on-task
      electrocortical responses in the prediction of inhibitory control errors. These
      data support the relevance of autonomic regulation in understanding age-related
      change in higher-order neurocognitive function.

PMID- 22410266
TI  - Immunology of bovine respiratory syncytial virus infection of cattle.
AB  - Bovine respiratory syncytial virus (BRSV) is a respiratory pathogen of cattle
      that causes severe disease in calves alone and as one of several viruses and
      bacteria that cause bovine respiratory disease complex. Like human RSV this virus
      modulates the immune response to avoid stimulation of a vibrant CD8+ T cytotoxic
      cell response and instead promotes a Th2 response. The Th2 skew sometimes results
      in the production of IgE antibodies and depresses production of the Th1 cytokine
      interferon gamma. Innate immune cells have a pivotal role in guiding the adaptive
      response to BRSV, with selective secretion of cytokines by pulmonary dendritic
      cells. Here we review some of the pertinent observations on immune responses to
      BRSV infection and vaccination and illustrate how experimental infection models
      have been used to elucidate the immunopathogenesis of BRSV infection. Recent
      experiments using intranasal vaccination and/or immune modulation with DNA based
      adjuvants show promise for effective vaccination by the stimulation of Th1 T cell
      responses.

PMID- 22410267
TI  - Effect of physical properties on the stability of Lactobacillus bulgaricus in a
      freeze-dried galacto-oligosaccharides matrix.
AB  - The ability of galacto-oligosaccharides (GOS) to protect Lactobacillus
      delbrueckii subsp. bulgaricus upon freeze drying was analyzed on the basis of
      their capacity to form glassy structures. Glass transition temperatures (T(g)) of
      a GOS matrix at various relative humidities (RH) were determined by DSC. Survival
      of L. bulgaricus in a glassy GOS matrix was investigated after freezing, freeze
      drying, equilibration at different RHs and storage at different temperatures. At
      32  degrees C, a drastic viability loss was observed. At 20  degrees C, the
      survival was affected by the water content, having the samples stored at lower
      RHs, the highest survival percentages. At 4 degrees C, no decay in the cells
      count was observed after 45 days of storage. The correlation between molecular
      mobility [as measured by Proton nuclear magnetic resonance (1H NMR)] and loss of
      viability explained the efficiency of GOS as cryoprotectants. The preservation of
      microorganisms was improved at low molecular mobility and this condition was
      obtained at low water contents and low storage temperatures. These results are
      important in the developing of new functional foods containing pre and
      probiotics.

PMID- 22410268
TI  - Sobriety as an admission criterion for transitional housing: a multi-site
      comparison of programs with a sobriety requirement to programs with no sobriety
      requirement.
AB  - BACKGROUND: This study examined whether homeless clients enrolled in transitional
      housing programs that required sobriety (SR) as an admission criterion have
      outcomes comparable to clients enrolled in programs that did not require sobriety
      (NSR) as an admission criterion. METHODS: A total of 1062 military veterans in 40
      transitional housing programs funded by the United States Department of Veterans
      Affairs were grouped based on whether they were in SR or NSR programs and
      followed over a one-year period after program discharge. Participants in SR and
      NSR programs were compared on their ratings of the social climate of the program,
      and housing and psychosocial outcomes. RESULTS: Participants in SR programs
      reported more days housed and better psychosocial outcomes than participants in
      NSR programs, although the differences were small and there were no differences
      in ratings of their social climate. Both participants in SR and NSR programs
      showed improvements on most outcomes after discharge from transitional housing.
      There were no significant differences in outcomes between participants actively
      abusing substances at program entry compared to those who were not. CONCLUSIONS:
      Requiring sobriety as an admission criterion in transitional housing made only a
      small difference in housing outcomes post-discharge. Further study is needed to
      determine whether requiring sobriety at admission in transitional housing is
      necessary for successful client outcomes.

PMID- 22410269
TI  - Civil unrest and birthweight: an exploratory analysis of the 2007/2008 Kenyan
      Crisis.
AB  - For decades, Africa has been plagued by political and ethnic conflict, the health
      ramifications of which are often not investigated. A crisis occurred recently in
      Kenya following the 2007 presidential election. Ethnic violence ensued, targeting
      the incumbent President Kibaki's Kikuyu people. The violence occurred primarily
      in Nairobi and the Rift Valley of Kenya. We sought to examine the association
      between exposure to the 2007/2008 Kenyan Crisis and birthweight. Using the
      2008/2009 Kenyan Demographic and Health Survey (KDHS), we compared birthweights
      of infants in utero or not yet conceived during the 15 months after the political
      turmoil following the 2007 presidential election (exposed) to those who were born
      before the crisis (unexposed). There were 663 "exposed" and 687 "unexposed"
      infants. Multivariate regression was used. We examined the possibility of two-way
      and three-way interactions between exposure status, ethnicity (Kikuyu versus non
      Kikuyu), and region (violent region versus not). Overall, exposure to the Kenyan
      Crisis was associated with lower birthweight. Kikuyu women living in a violent
      region who were exposed during their 2nd trimester had the greatest difference in
      birthweight in comparison to all unexposed infants: 564.4g lower (95% CI 285.1,
      843.6). Infants of Kikuyu exposed during the 2nd trimester and living in a
      violent region weighed 603.6g less (95% CI 333.6, 873.6) than Kikuyu infants born
      during the unexposed period. Political unrest may have implications for the
      birthweight of infants, particularly among targeted populations. Given the
      adverse sequelae associated with lowered birthweight, these results suggest that
      particular attention should be paid to pregnant women and targeted ethnic groups
      following such events.

PMID- 22410270
TI  - Network social capital, social participation, and physical inactivity in an urban
      adult population.
AB  - Research on individual social capital and physical activity has tended to focus
      on the association among physical activity, generalized trust, and social
      participation. Less is known about the association between network social
      capital, i.e., the resources accessed through one's social connections, and
      physical inactivity. Using formal network measures of social capital, this study
      examined which specific dimension of network capital (i.e. diversity, reach and
      range) was associated with physical inactivity, and whether network social
      capital mediated the association between physical inactivity and social
      participation. Data came from the 2008 Montreal (Canada) Neighbourhood Networks
      and Healthy Aging survey, in which 2707 adults 25 years and older in 300 Montreal
      neighbourhoods were surveyed. Physical activity was self-reported using the
      International Physical Activity Questionnaire (IPAQ). IPAQ guidelines provided
      the basis for the physical inactivity cutoff. Network social capital was measured
      with a position generator instrument. Multilevel logistic methods were used to
      examine the association between physical inactivity and individual social capital
      dimensions, while adjusting for socio-demographic and -economic factors. Higher
      network diversity was associated with a decreased likelihood of physical
      inactivity. Consistent with previous findings, individuals who did not
      participate in any formal associations were more likely to be physically inactive
      compared to those with high levels of participation. Network diversity mediated
      the association between physical inactivity and participation. Generalized trust
      and the network components of reach and range were not shown associated with
      physical inactivity. Findings highlight the importance of social participation
      and network social capital and the added value of network measures in the study
      of social capital and physical inactivity. Population-based programs targeting
      physical inactivity among adults might consider ecological-level interventions
      that leverage associational involvement and interpersonal relationships to
      improve population-level physical activity.

PMID- 22410271
TI  - Knowledge, attitude and practice of emergency contraceptive among women who seek
      abortion care at Jimma University specialized hospital, southwest Ethiopia.
AB  - BACKGROUND: In Ethiopia maternal mortality rate is very high more than one in
      five women die from pregnancy or pregnancy related causes. The use of
      contraceptives to prevent unwanted pregnancies and unsafe abortion is an
      important strategy to minimize maternal mortality rate. Among various forms of
      contraception, emergency contraceptives are the only one that can be used after
      sexual intercourse offering chance to prevent unwanted pregnancy. The aim of this
      study was to assess the knowledge, attitude and practice of emergency
      contraceptive among women who seek abortion care at Jimma University specialized
      hospital (JUSH). METHODS: Institution base cross-sectional study on knowledge,
      attitude and practice of emergency contraceptive was conducted at JUSH from April
      to June, 2011 Data was collected using structured questionnaire and analyzed
      using SPSS version 17.0. RESULTS: In this study 89 women were interviewed. More
      than half of them (48) were from urban area and 41 were from rural area.46
      (51.7%) of them were single. Of all the respondents only nine women had awareness
      about emergency contraceptive. Seven of the women mentioned pills as emergency
      contraception and only two of them mentioned both pills and injectable as
      emergency contraception. All of them have positive attitude towards emergency
      contraception but none of them have ever used emergency contraceptives.
      CONCLUSION AND RECOMMENDATION: The finding revealed pregnancy among women of 15
      19 years was very common. The knowledge and practice of emergency contraception
      is very low. But there is high positive attitude towards emergency
      contraceptives. Since there is much deficit on knowledge of women on emergency
      contraceptives, in addition to making them accessible; programs targeted at
      promotion and education of emergency contraceptives is helpful to prevent
      unwanted pregnancy.

PMID- 22410272
TI  - Lip reconstruction: an anthropometric and functional analysis of surgical
      outcomes.
AB  - Postoperative evaluation of results of reconstructive procedures of the lips
      mainly consists of describing the technique, complications and subjectively
      interpreted patient photographs. The authors present a photo-assisted pre- to
      postoperative evaluation of reconstructive procedures of the lips based on
      anthropometric measurements and functional outcome. Forty-eight patients
      underwent partial or full thickness excision of tumours of the lips and
      subsequent reconstruction. An analysis of standardized pre- and postoperative
      photographs included measurements of intercanthal width, mouth width, philtrum
      width, lateral upper lip height, upper and lower lip height, cutaneous upper and
      lower lip height, upper and lower vermilion arc and upper and lower vermilion
      height. Assessment of functional outcome consisted of the evaluation of oral
      competence, changes of oral opening and sensation. The effects on the described
      parameters were analysed, when partial or full thickness reconstruction had to be
      performed. Intercanthal mouth width index, vermilion arc index, vermilion and
      cutaneous total lower lip height index showed statistically significant effects
      postoperatively which indicates a postoperative tightened lower lip, when full
      thickness excision was performed. In all patients the indices were proven
      reproducible and reliable. The standardized measurements described are accurate
      and objective for evaluating postoperative results.

PMID- 22410273
TI  - An improved competitive inhibition enzymatic immunoassay method for tetrodotoxin
      quantification.
AB  - Quantifying tetrodotoxin (TTX) has been a challenge in both ecological and
      medical research due to the cost, time and training required of most
      quantification techniques. Here we present a modified Competitive Inhibition
      Enzymatic Immunoassay for the quantification of TTX, and to aid researchers in
      the optimization of this technique for widespread use with a high degree of
      accuracy and repeatability.

PMID- 22410274
TI  - Health impact of probiotics - vision and opportunities.
AB  - Our understanding of the role of the microbiota in our gut and other sites in
      our body is rapidly emerging and could lead to many new and innovative approaches
      for health care. The promise of the potential role of probiotics for the
      prevention and treatment of enteric and other infections as an effective solution
      needs to be realized. The meeting report summarizes the insights and learning
      from a recent symposium, "Health Impact of Probiotics - Vision and Opportunities"
      conducted in Mumbai by the Yakult India Microbiota and Probiotic Science
      Foundation and P.D. Hinduja National Hospital, Mumbai. The symposium reflected
      its objective of unraveling the potential role of probiotics for health benefits
      through presentations and discussions. Experts clearly highlighted the role of
      probiotics in improving various aspects of health and in immune modulation. The
      report also captures the debate and discussions on the challenges that are likely
      to be encountered for the use of probiotics in the country.

PMID- 22410275
TI  - WITHDRAWN: Ultrastructure of the human retina in aging and various pathological
      states.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 22410276
TI  - Cytopathological potato virus Y structures during Solanaceous plants infection.
AB  - The ultrastructural analysis of tobacco, potato and pepper tissues during
      infection with necrotic strains and the ordinary Potato virus Y strain of
      revealed the presence of virus inclusions not only in the epidermis and mesophyll
      but also in the vascular tissues. For the first time cytoplasmic inclusions were
      documented in companion cells and phloem parenchyma as well as in xylem tracheary
      elements. The ultrastructural features studied in this work consisted of mostly
      laminated inclusions (in the traverse and longitudinal section), which were
      frequently connected with enlarged cisternae of endoplasmic reticulum (ER)
      located in the direct vicinity of the cell wall attached to virus particles
      opposite to plasmodesmata. It was noticed that ER participates in synthesis and
      condensation of the PVY inclusions. During compatible interaction of tobacco and
      potato plants with PVY, amorphous and nuclear inclusions were observed. Such
      forms were not found in pepper tissues and potato revealing the hypersensitivity
      reaction to the infection with PVY necrotic strains. It was stated that the forms
      of cytoplasmic inclusions cannot serve as a cytological criterion to distinguish
      the potato virus Y strains and do not depend on host resistance level. Only in
      compatible interaction in Solanaceous plants tissues cytoplasmic inclusions were
      observed from the moment the morphological symptoms appeared. In the reaction of
      hypersensitivity, the inclusions were found on the 24th day following the
      infection with the PVY necrotic strains, whereas the symptoms were observed 3
      days after the PVY infection.

PMID- 22410277
TI  - Successful pregnancy outcome following gamete intra-Fallopian transfer in a
      patient with Mullerian dysgenesis.
AB  - A 29-year-old lady with Mullerian dysgenesis was keen to have a baby. Clinically,
      she was medium built with well-developed secondary female sexual characteristics.
      There was a short and blind vagina. She had undergone surgery for an imperforated
      hymen. Her FSH and LH concentrations were normal. Laparoscopy revealed a patent
      right Fallopian tube, a rudimentary right uterus and extensive pelvic
      endometriosis. She subsequently underwent gamete intra-Fallopian transfer (GIFT).
      Oocyte retrieval was carried out laparoscopically and a total of nine oocytes
      were retrieved. Four of the oocytes were transferred together with motile
      spermatozoa into the right Fallopian tube and the remaining five oocytes were
      inseminated with spermatozoa for IVF. Three embryos resulted and were frozen. She
      subsequently developed moderate ovarian hyperstimulation syndrome. Serum beta
      human chorionic gonadotrophin concentration 14 days after GIFT was 1612 IU/l. Her
      antenatal care was relatively uneventful until 31 weeks of gestation when she was
      diagnosed to have intrauterine growth retardation and oligohydramnios. She then
      underwent an emergency Caesarean section at 32 weeks of pregnancy delivering a
      normal baby. This case study describes a successful pregnancy outcome following
      gamete intra-Fallopian transfer (GIFT) in a woman with malformation of the vagina
      (Mullerian dysgenesis). A 29-year-old lady with Mullerian dysgenesis diagnosed at
      16 years of age was keen to become pregnant. Upon examination, a decision was
      made for a William's vulvovaginoplasty but as the patient was indecisive the
      surgery was deferred. Clinically, she is a medium-built lady with well-developed
      secondary female sexual characteristics. There was a short and blind vagina. Her
      serum FSH and LH concentrations were normal. Laparoscopy revealed a patent right
      Fallopian tube, a rudimentary right uterus and extensive pelvic endometriosis.
      She subsequently underwent GIFT. Nine oocytes were retrieved through laparoscopy.
      Four of the oocytes were transferred together with motile sperm into the right
      Fallopian tube and the remaining five oocytes were inseminated with sperm for
      IVF. Three embryos resulted and were frozen. Serum beta human chorionic
      gonadotrophin concentration measured 14 days after GIFT was 1612 IU/l. An
      abdominal ultrasonography performed at 5 weeks showed one intrauterine
      gestational sac. Her antenatal care was uneventful until 31 weeks of gestation
      when she developed a deficiency of amniotic fluid in the amniotic sac. She then
      underwent an emergency Caesarean section at 32 weeks of pregnancy. She delivered
      a healthy, normal 1.24 kg baby boy. Her post-natal care was uneventful.

PMID- 22410278
TI  - Impact of non-neurological complications in severe traumatic brain injury
      outcome.
AB  - INTRODUCTION: Non-neurological complications in patients with severe traumatic
      brain injury (TBI) are frequent, worsening the prognosis, but the pathophysiology
      of systemic complications after TBI is unclear. The purpose of this study was to
      analyze non-neurological complications in patients with severe TBI admitted to
      the ICU, the impact of these complications on mortality, and their possible
      correlation with TBI severity. METHODS: An observational retrospective cohort
      study was conducted in one multidisciplinary ICU of a university hospital (35
      beds); 224 consecutive adult patients with severe TBI (initial Glasgow Coma Scale
      (GCS) < 9) admitted to the ICU were included. Neurological and non-neurological
      variables were recorded. RESULTS: Sepsis occurred in 75% of patients, respiratory
      infections in 68%, hypotension in 44%, severe respiratory failure (arterial
      oxygen pressure/oxygen inspired fraction ratio (PaO2/FiO2) < 200) in 41% and
      acute kidney injury (AKI) in 8%. The multivariate analysis showed that Glasgow
      Outcome Score (GOS) at one year was independently associated with age, initial
      GCS 3 to 5, worst Traumatic Coma Data Bank (TCDB) first computed tomography (CT)
      scan and the presence of intracranial hypertension but not AKI. Hospital
      mortality was independently associated with initial GSC 3 to 5, worst TCDB first
      CT scan, the presence of intracranial hypertension and AKI. The presence of AKI
      regardless of GCS multiplied risk of death 6.17 times (95% confidence interval
      (CI): 1.37 to 27.78) (P < 0.02), while ICU hypotension increased the risk of
      death in patients with initial scores of 3 to 5 on the GCS 4.28 times (95% CI:
      1.22 to 15.07) (P < 0.05). CONCLUSIONS: Low initial GCS, worst first CT scan,
      intracranial hypertension and AKI determined hospital mortality in severe TBI
      patients. Besides the direct effect of low GCS on mortality, this neurological
      condition also is associated with ICU hypotension which increases hospital
      mortality among patients with severe TBI. These findings add to previous studies
      that showed that non-neurological complications increase the length of stay and
      morbidity in the ICU but do not increase mortality, with the exception of AKI and
      hypotension in low GCS (3 to 5).

PMID- 22410279
TI  - The leucine aminopeptidase of Staphylococcus aureus is secreted and contributes
      to biofilm formation.
AB  - BACKGROUND: Staphylococcus aureus has emerged as a major drug-resistant pathogen
      in hospital- and community-acquired infections. Leucine aminopeptidase (LAP) is
      known to be essential for survival of the bacteria; however the LAP of S. aureus
      has not been extensively characterized. In this study, we report a detailed
      characterization of the S. aureus LAP. METHODS: LAP from S. aureus was cloned,
      purified, and further biochemically characterized. The expression of LAP was
      analyzed by Western blotting. Growth and biofilm formation were analyzed
      spectrophotometrically. RESULTS: LAP was cloned from S. aureus and expressed as a
      55 kDa protein, whereas the molecular weight of the native protein is
      approximately 600 kDa. LAP showed amidolytic activity against l-leucine p
      nitroanilide. Optimal activity was observed at pH 8.5 and 37 degrees C with a
      V(max) of 2500MUmol/min/mg protein. LAP enzymatic activity was inhibited by ion
      chelators and enhanced by divalent metal ions, specifically Ni. LAP is secreted
      by laboratory as well as clinical strains. Bestatin, an inhibitor of LAP,
      inhibits S. aureus growth and biofilm formation. CONCLUSIONS: To our knowledge,
      this is the first detailed characterization of LAP from S. aureus and suggests
      its importance in survival and pathogenesis.

PMID- 22410280
TI  - Intramyocardial injections of human mesenchymal stem cells following acute
      myocardial infarction modulate scar formation and improve left ventricular
      function.
AB  - Cell therapy is a promising treatment modality to improve heart function in acute
      myocardial infarction. However, the mechanisms of action and the most suitable
      cell type have not been finally determined. We performed a study to compare the
      effects of mesenchymal stem cells (MSCs) harvested  from different tissues on LV
      function and explore their effects on tissue structure by morphometry and
      histological staining for species and lineage relationship. MSCs from skeletal
      muscle (SM-MSCs) and adipose tissue (ADSCs) were injected in the myocardium of
      nude rats 1 week after myocardial  infarction. After 4 weeks of observation, LVEF
      was significantly improved in the SM-MSCs group (39.1%) and in the ADSC group
      (39.6%), compared to the placebo group (31.0%, p < 0.001 for difference in change
      between groups). Infarct size was smaller after cell therapy (16.3% for SM-MSCs, 
      15.8% for ADSCs vs. 26.0% for placebo, p < 0.001), and the amount of highly
      vascularized granulation tissue in the border zone was significantly increased in
      both groups receiving MSCs (18.3% for SM-MSCs, 22.6% for ADSCs vs. 13.1% for
      placebo, p = 0.001). By in situ hybridization,  moderate engraftment of
      transplanted cells was found, but no transdifferentiation to cardiomyocytes,
      endothelial cells, or smooth muscle cells was observed. We conclude that MSC
      injections lead to improved LVEF after AMI in rats predominantly by reduction of
      infarct size. After 4 weeks, we  observed modulation of scar formation with
      significant increase in granulation tissue. Transdifferentiation of MSCs to
      cardiomyocytes or vascular cells did not contribute significantly in this
      process. MSCs from skeletal muscle and adipose tissue had similar effects.

PMID- 22410281
TI  - A fluorescence polarization binding assay to identify inhibitors of flavin
      dependent monooxygenases.
AB  - N-Hydroxylating monooxygenases (NMOs) are essential for pathogenesis in fungi and
      bacteria. NMOs catalyze the hydroxylation of sine and ornithine in the
      biosynthesis of hydroxamate-containing siderophores. Inhibition of kynurenine
      monooxygenase (KMO), which catalyzes the conversion of kynurenine to 3
      hydroxykynurenine, alleviates neurodegenerative disorders such as Huntington's
      and Alzheimer's diseases and brain infections caused by the parasite Trypanosoma
      brucei. These enzymes are examples of flavin-dependent monooxygenases, which are
      validated drug targets. Here, we describe the development and optimization of a
      fluorescence polarization assay to identify potential inhibitors of flavin
      dependent monooxygenases. Fluorescently labeled ADP molecules were synthesized
      and tested. An ADP-TAMRA chromophore bound to KMO with a K(d) value of 0.60 +/-
      0.05 MUM and to the NMOs from Aspergillus fumigatus and Mycobacterium smegmatis
      with K(d) values of 2.1 +/- 0.2 and 4.0 +/- 0.2 MUM, respectively. The assay was
      tested in competitive binding experiments with substrates and products of KMO and
      an NMO. Furthermore, we show that this assay can be used to identify inhibitors
      of NMOs. A Z' factor of 0.77 was calculated, and we show that the assay exhibits
      good tolerance to temperature, incubation time, and dimethyl sulfoxide
      concentration.

PMID- 22410282
TI  - Uveitis with retinal occlusive vasculitis and sensorineural hypoacusia as first
      symptoms of relapsing polychondritis.
AB  - We herein describe an atypical case of relapsing polychondritis, presenting
      initially with isolated ocular signs characterised by uveitis and retinal
      occlusive vasculitis preceded by 10 years of auricular and laringothracheal
      chondritis. This case highlights the importance of considering connective tissue
      inflammatory conditions in any retinal vasculitis. A systemic enquiry is
      invaluable in order to avoid a delayed diagnosis and the subsequent associated
      complications and mortality.

PMID- 22410283
TI  - Primary pulmonary leiomyosarcoma -- a case report.
AB  - Sarcomas are mesenchymal tumors that originate from the stromal elements of the
      bronchial wall or from interstices of lung parenchyma. Pulmonary sarcomatous
      neoplasms are a rare and diagnostically challenging group of tumors. They
      constitute only 0.2%-0.5% of all primary lung malignancies. Primary pulmonary
      leiomyosarcomas are subdivided into those originating from pulmonary parenchyma,
      bronchial tree or pulmonary arteries. Here we present a case of 43-year-old
      African-American female who with chronic cough, fatigue and weight loss. Early
      detection is the key to the successful management of these patients. The
      available treatment option is complete resection of tumor. These cases provide an
      interesting juxtaposition to the management of typical lung cancer.

PMID- 22410284
TI  - Allergy as an epithelial barrier disease.
AB  - The objective of this review is to focus on putative modified epithelial
      functions related to allergy. The dysregulation of the epithelial barrier might
      result in the allergen uptake, which could be the primary defect in the
      pathogenesis of allergic reaction. We review the literature of the role of
      respiratory epithelium as an active barrier, how allergens are transported
      through it and how it senses the hostile environmental allergens and other
      dangerous stimuli.

PMID- 22410285
TI  - Tug 'O' war: challenges of transverse upper gracilis (TUG) myocutaneous free flap
      breast reconstruction.
AB  - Autologous tissue microsurgical breast reconstruction is increasingly requested
      by women following mastectomy. While the abdomen is the most frequently used
      donor site, not all women have enough abdominal tissue excess for a unilateral or
      bilateral breast reconstruction. A secondary choice in such women may be the
      transverse upper gracilis (TUG) myocutaneous flap. This study reviews our
      experience with TUG flap breast reconstruction looking specifically at
      reconstructive success rate and the requirement for secondary surgery. A total of
      16 free TUG flaps were performed to reconstruct 15 breasts in eight patients over
      a period of five years. Data were collected retrospectively by chart review.
      Follow up ranged from 14 to 41 months. During the follow up period, there was one
      (6.3%) complete flap loss in an immediate breast reconstruction patient. Four
      further flaps (25%) failed in their primary aim of breast reconstruction, as they
      required additional significant reconstruction with either deep inferior
      epigastric perforator (DIEP) flaps (two flaps (12.5%), one patient) or
      augmentation with silicone breast implants (two flaps (12.5%), one patient),
      giving a successful breast reconstruction rate with the TUG flap of only 66.7%.
      In all of the remaining reconstructed breasts, deficient flap volume or breast
      contour was seen. Eight flaps were augmented by lipofilling. A total of 62.5% of
      the donor sites had complications, namely sensory disturbance of the medial thigh
      (25%) and poor scar (37.5%) requiring revision. This series demonstrates a high
      rate of reconstructive failure and unsatisfactory outcomes from TUG flap breast
      reconstruction. We feel this reinforces the necessity of adequate pre-operative
      patient assessment and counselling, including discussion regarding the likelihood
      of subsequent revisional surgery, before embarking on this form of autologous
      breast reconstruction.

PMID- 22410286
TI  - Emergence of HIV-1 drug resistance mutations among antiretroviral-naive HIV-1
      infected patients after rapid scaling up of antiretroviral therapy in Thailand.
AB  - BACKGROUND: After rapid scaling up of antiretroviral therapy in HIV-1-infected
      patients, the data of primary HIV-1 drug resistance in Thailand is still limited.
      This study aims to determine the prevalence and associated factors of primary HIV
      1 drug resistance in Thailand. METHODS: A prospective observational study was
      conducted among antiretroviral-naive HIV-1-infected Thai patients from 2007 to
      2010. HIV-1 subtypes and mutations were assayed by sequencing a region of HIV-1
      pol gene. Surveillance drug resistance mutations recommended by the World Health
      Organization for surveillance of transmitted HIV-1 drug resistance in 2009 were
      used in all analyses. Primary HIV-1 drug resistance was defined as the presence
      of one or more surveillance drug resistance mutations. RESULTS: Of 466 patients
      with a mean age of 38.8 years, 58.6% were males. Risks of HIV-1 infection
      included heterosexual (77.7%), homosexual (16.7%), and intravenous drug use
      (5.6%). Median (IQR) CD4 cell count and HIV-1 RNA were 176 (42-317) cells/mm(3)
      and 68,600 (19,515-220,330) copies/mL, respectively. HIV-1 subtypes were CRF01_AE
      (86.9%), B (8.6) and other recombinants (4.5%). The prevalence of primary HIV-1
      drug resistance was 4.9%; most of these (73.9%) had surveillance drug resistance
      mutations to only one class of antiretroviral drugs. The prevalence of patients
      with NRTI, NNRTI, and PI surveillance drug resistance mutations was 1.9%, 2.8%
      and 1.7%, respectively. From logistic regression analysis, there was no factor
      significantly associated with primary HIV-1 drug resistance. There was a trend
      toward higher prevalence in females [odds ratio 2.18; 95% confidence interval
      0.896-5.304; p = 0.086]. CONCLUSIONS: There is a significant emergence of primary
      HIV-1 drug resistance in Thailand after rapid scaling up of antiretroviral
      therapy. Although HIV-1 genotyping prior to antiretroviral therapy initiation is
      not routinely recommended in Thailand, our results raise concerns about the risk
      of early treatment failure in patients with primary HIV-1 drug resistance.
      Interventions to prevent the transmission of HIV-1 drug resistance and
      continuation of surveillance for primary HIV-1 drug resistance in Thailand are
      indicated.

PMID- 22410287
TI  - Insulin stimulates IGFBP-2 expression in 3T3-L1 adipocytes through the PI3K/mTOR
      pathway.
AB  - Insulin-like growth factor binding protein 2 (IGFBP-2) has been implicated in the
      etiology of several diseases, including the metabolic syndrome. Although IGFBP-2
      derives mostly from the liver, recent evidence in mice and humans indicate that
      aging and obesity are associated with altered IGFBP-2 levels in white adipocytes.
      The present study was aimed at determining the mechanisms that control IGFBP-2
      expression in mature adipocytes. IGFBP-2 mRNA and protein expression in serum
      deprived 3T3-L1 adipocytes were twofold increased by acute insulin treatment. Co
      treatments with the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin or
      the mammalian target of rapamycin (mTOR) inhibitor rapamycin blunted the effects
      of insulin. Coherently, IGFBP-2 mRNA levels were robustly increased in adipocytes
      lacking either TSC2 or 4E-BP1. Insulin triggered the recruitment of CAAT/enhancer
      binding protein alpha (C/EBPalpha) to the IGFBP-2 proximal promoter. These
      findings suggest that insulin upregulates IGFBP-2 expression through a
      PI3K/mTOR/C/EBPalpha pathway in white adipocytes.

PMID- 22410288
TI  - Discovery of novel sulfonamides as potent and selective inhibitors against human
      and mouse 11beta-hydroxysteroid dehydrogenase type 1.
AB  - Several classes of non-steroid 11beta-HSD1 inhibitors have been developed as
      promising treatments for Type 2 Diabetes (T2D). Using a human 11beta-HSD1
      selective inhibitor as a starting point, we designed and synthesized a new class
      of derivatives of 1-arylsulfonyl piperidine-3-carboxamides. It was found that the
      large lipophilic group on the amino moiety may lead to cross-species potency
      towards human and mouse, allowing drug development by evaluating compounds in
      rodent model. By exploring structure-activity-relationship, the (R)-(+)
      bornylamine derivative is identified as the most potent inhibitor of mouse enzyme
      11beta-HSD1 with an IC(50) of 18 nM. Docking studies revealed the different
      possible interaction modes of the S-enantiomer and R-enantiomer bound to h11beta
      HSD1, and explained why the S-enantiomer is more active than the R-enantiomer.
      Finally, two potent and isoform-selective compounds, (+)-isopinocampheylamine
      derivative 8m and (R)-(+)-bornylamine derivative 8l, with suitable in vitro
      properties, could be selected for future PK/PD evaluation in rodent models. Then,
      8l was subjected a pharmacodynamics study in vivo with rodent model. It was shown
      that 8l have 71% and 63% inhibition in adipose and liver tissue at 1h after
      administration, but it was a short-acting compound displaying a significant drop
      in potency in the subsequent 3h. This study not only provides compounds as novel
      h11beta-HSD1 inhibitors, but also presents structure-activity relationships for
      designing potent human/mouse 11beta-HSD1 inhibitors suitable for in vivo
      evaluation in rodent models.

PMID- 22410289
TI  - Pharmacokinetic interaction between pitavastatin and valsartan: a randomized,
      open-labeled crossover study in healthy male Korean volunteers.
AB  - BACKGROUND: Pitavastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase, and valsartan, an angiotensin receptor blocker, are used
      concurrently in some patients who are both hyperlipidemic and hypertensive.
      However, to date, no published studies have explored whether there is an
      interaction between pitavastatin and valsartan. OBJECTIVE: The aim of this study
      was to investigate the potential pharmacokinetic interaction between pitavastatin
      and valsartan in healthy male volunteers in Korea. METHODS: A randomized, open
      label crossover study was conducted in healthy male Korean volunteers. In varying
      sequences, each subject received pitavastatin 2 * 2 mg, valsartan 2 * 160 mg, and
      both treatments, once daily for 7 consecutive days, with a 7-day washout period
      between each treatment period. Plasma samples were obtained at steady state for
      the pharmacokinetic evaluation of pitavastatin and valsartan. Pharmacodynamic
      assessment included lipid profiles and vital sign measurements (systolic and
      diastolic blood pressure [SBP and DBP, respectively] and pulse rate [PR]). A
      safety profile assessment, which included vital sign measurements, ECG, and
      clinical laboratory testing, was performed in each subject. RESULTS: A total of
      24 subjects were enrolled (mean age, 30.5 years [range, 23.0-45.0 years]; mean
      body weight, 71.2 kg [range, 56.1-86.0 kg]; and mean body mass index, 23.2
      kg/m(2) [range, 19.2-25.8 kg/m(2)]). The 95% CIs of the geometric mean ratios of
      AUC(tau) and C(max,ss) of pitavastatin were 0.97 to 1.11 and 0.73 to 1.09,
      respectively. The 95% CIs of the geometric mean ratios of AUC(tau) and C(max,ss)
      of valsartan were 0.90 to 1.27 and 0.81 to 1.29. Pitavastatin administered as
      monotherapy and in combination with valsartan was associated with significantly
      lowered total cholesterol and LDL-C compared with valsartan monotherapy (both, P
      < 0.05). Differences in lipid-lowering effects were not statistically significant
      between pitavastatin monotherapy and pitavastatin combined with valsartan.
      Valsartan monotherapy and valsartan combined with pitavastatin were associated
      with significantly lower SBP and DBP compared with baseline (both, P < 0.05),
      although no significant changes in PR were observed. No significant differences
      in BP or PR changes were noted between concurrent administration of valsartan
      monotherapy compared with pitavastatin + valsartan. There were no serious AEs
      reported, and none of the subjects discontinued the study due to AEs.
      CONCLUSIONS: The pharmacokinetic profiles of pitavastatin and valsartan
      administered as monotherapy were comparable to combination treatment in these
      healthy male Korean volunteers, suggesting that individual pharmacokinetic
      properties are not significantly affected by concurrent administration. The
      concurrent administration of pitavastatin and valsartan was generally well
      tolerated. The findings from the present study provide a basis for a larger study
      in hypertensive patients with hyperlipidemia.

PMID- 22410290
TI  - Oral administration of collagen tripeptide improves dryness and pruritus in the
      acetone-induced dry skin model.
AB  - BACKGROUND: Dry skin causes pruritus and discomfort in patients with xerosis and
      atopic dermatitis. General treatment for skin dryness involves the topical
      application of an emollient. However, more effective, simpler therapies are
      desired. Collagen tripeptide (CTP) is a highly purified, non-antigenic, low
      allergenic collagen fraction that is known to have various biological effects.
      OBJECTIVE: To clarify the therapeutic effects of CTP for dry skin using acetone
      induced dry skin model mice. METHODS: ICR mice were treated with acetone followed
      by oral administration of CTP (80 or 500mg/kg/day) for 3 days. Hyaluronic acid
      production induced by CTP was assessed using human dermal fibroblasts in vitro
      and in an acetone-induced dry skin model mice in vivo. Transepidermal water loss
      (TEWL) and scratching behavior were evaluated. Furthermore, the effects of CTP on
      intraepidermal nerve fibers and expression of semaphorin 3A (Sema3A) and nerve
      growth factor (NGF) were examined by immunohistochemistry and quantitative RT
      PCR. RESULTS: CTP enhanced hyaluronic acid production in human dermal fibroblasts
      in vitro and in murine skin in vivo. Oral administration of CTP in acetone
      induced dry skin model mice significantly decreased TEWL and suppressed
      scratching behavior. Intraepidermal nerve growth was dramatically inhibited in
      CTP-treated mice. Quantitative PCR analysis and immunohistochemical study
      revealed that CTP abolished the increased NGF and decreased Sema3A levels induced
      by acetone treatment. CONCLUSION: Oral administration of CTP improves dry skin
      and normalizes axon-guidance factors in the epidermis in addition to reducing
      pruritus. CTP may be used in a new therapeutic strategy against dry skin and
      pruritus.

PMID- 22410291
TI  - Resveratrol attenuates brain damage in a rat model of focal cerebral ischemia via
      up-regulation of hippocampal Bcl-2.
AB  - A number of studies have demonstrated that resveratrol (Res), a natural
      polyphenol compound found in plants, shows potent neuroprotective, anti
      inflammatory and antioxidant effects; however, its ability to prevent ischemia
      induced brain damage remains unclear. Here we tested whether Res played a
      neuroprotective role in a rat brain ischemia model induced by middle cerebral
      artery occlusion (MCAO). Adult male rats were randomly assigned into four
      experimental groups: sham operation (sham), ischemia treatment (MCAO), Res
      treated MCAO (Res+MCAO) and Res alone group (Res+sham). The brain damage size and
      hippocampal apoptotic neurons in each rat were evaluated by triphenyltetrazolium
      chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP
      nick end labeling (TUNEL) staining, respectively. Long-term potentiation (LTP)
      induced by high-frequency stimulation (HFS) in the hippocampus was assessed with
      extracellular recording. The expression of apoptosis-related proteins, i.e., Bcl
      2 and Bax, in the hippocampus was detected by western blot. Our results revealed
      that Res treatment significantly reduced brain infarct volume of MCAO rats as
      compared to MCAO rats without Res treatment. A significant increase in TUNEL
      positive neurons in the hippocampal CA1 region was visualized in the MCAO rats as
      compared to that of the sham group, but this increase was attenuated with Res
      treatment. Functionally, extracellular recordings revealed that MCAO operation
      impaired LTP in the hippocampal CA1 region and the basal synaptic transmission
      between the Schaffer collaterals, whereas Res treatment rescued the impaired LTP
      and facilitated synaptic transmission in the CA1 region of the MCAO rats. Res
      treatment increased the expression of anti-apoptotic protein Bcl-2 and decreased
      the expression of pro-apoptotic protein Bax in the MCAO rats. The findings
      suggest that Res can attenuate the deleterious effects of focal cerebral
      ischemia/reperfusion-induced brain injury and function as a potential
      neuroprotective agent. The neuroprotective qualities of Res, based on our data,
      may be attributable to the up-regulation of Bcl-2 expression and down-regulation
      of Bax expression.

PMID- 22410293
TI  - Properties of I(A) in a neuron of the dorsal raphe nucleus.
AB  - Voltage clamp data were analyzed in order to characterize the properties of the
      fast potassium transient current I(A) for a presumed serotonergic neuron of the
      rat dorsal raphe nucleus (DRN). We obtain maximal conductance, time constants of
      activation and inactivation, and the steady state activation and inactivation
      functions m(infinity) and h(infinity), as Boltzmann curves, defined by half
      activation potentials and slope factors. I(A) is estimated as g-(V-V(rev))m(4)h,
      with g-=20.5nS. For activation, the half-activation potential is V(a)=-52.5mV
      with slope factor k(a)=16.5mV, whereas for inactivation the corresponding
      quantities are -91.5mV and -9.3mV. We discuss the results in terms of the
      corresponding properties of I(A) in other cell types and their possible relevance
      to pacemaking activity in cells of the DRN. Methods of identification of
      serotonergic DRN neurons and the nature of the K(v) channels underlying the A
      type current are also discussed.

PMID- 22410292
TI  - Ethanol reduces the phase locking of neural activity in human and rodent brain.
AB  - How the neuromolecular actions of ethanol translate to its observed intoxicating
      effects remains poorly understood. Synchrony of phase (phase locking) of event
      related oscillations (EROs) within and between different brain areas has been
      suggested to reflect communication exchange between neural networks and as such
      may be a sensitive and translational measure of ethanol's effects. Using a
      similar auditory event-related potential paradigm in both rats and humans we
      investigated the phase variability of EROs collected from 38 young men who had
      participated in an ethanol/placebo challenge protocol, and 46 adult male rats
      given intraperitoneal injections of ethanol/saline. Phase locking was
      significantly higher in the delta frequencies in humans than in rats. Phase
      locking was also higher for the rare (target) tone than the frequent (non-target)
      tone in both species. Significant reductions in phase locking to the rare
      (target) tone in the delta, theta, alpha, beta and gamma frequencies, within and
      between brain sites, was found at 1h following ethanol as compared to
      placebo/saline administration in both rats and humans. Reductions in phase
      locking in the alpha frequencies in the parietal cortex were found to be
      correlated with blood ethanol concentrations. These findings are consistent with
      the hypothesis that ethanol's intoxicating actions in the brain include reducing
      synchrony within and between neuronal networks, perhaps by increasing the level
      of noise in key neuromolecular interactions.

PMID- 22410294
TI  - Expression of mutant N-terminal huntingtin fragment (htt552-100Q) in astrocytes
      suppresses the secretion of BDNF.
AB  - Huntington's disease (HD) is an inheritable neurological disorder caused by an
      abnormal expansion of the polyglutamine tract in the N-terminus of the protein
      huntingtin (htt). Mutant htt (mhtt) leads to selective neurodegeneration that
      preferentially affects striatal medium spiny neurons. Although mhtt is also
      expressed in astrocytes, whether and how astrocyte derived mhtt contributes to
      the neurodegeneration in HD remains largely unknown. In this study, a glia HD
      model, using an adenoviral vector to express wild-type and mutant N-terminal
      huntingtin fragment 1-552 aa (htt552) in rat primary cortical astrocytes, was
      generated. The influence of htt552 on the protein level of brain-derived
      neurotrophic factor (BDNF) in astrocytes was evaluated. Immunofluorescence showed
      that htt552-100Q formed aggregates in some astrocytes. These mhtt aggregates
      sequestered clathrin immunoreactivities and dispersed the Golgi complex. ELISA
      and immunofluorescence demonstrated an increase in BDNF levels in the astrocytes
      expressing htt552-100Q. Western blot analysis showed that there was an increase
      in pro-BDNF, but a decrease in mature BDNF in the astrocytes expressing htt552
      100Q. Furthermore, medium collected from astrocytes expressing htt552-100Q showed
      a lower level of mature BDNF and less activity in supporting neurite development
      of primary cortical neurons. These results suggest that aggregates formed by
      mutant htt552 affect processing and secretion of the BDNF in astrocytes, which
      might contribute to the neuronal dysfunction and degeneration in HD.

PMID- 22410295
TI  - Evaluation of chemiluminescence, toluidine blue and histopathology for detection
      of high risk oral precancerous lesions: A cross-sectional study.
AB  - BACKGROUND: Early detection holds the key to an effective control of cancers in
      general and of oral cancers in particular. However, screening procedures for oral
      cancer are not straightforward due to procedural requirements as well as
      feasibility issues, especially in resource-limited countries. METHODS: We
      conducted a cross-sectional study to compare the performance of
      chemiluminescence, toluidine blue and histopathology for detection of high-risk
      precancerous oral lesions. We evaluated 99 lesions from 55 patients who underwent
      chemiluminescence and toluidine blue tests along with biopsy and
      histopathological examination. We studied inter-as well as intra-rater agreement
      in the histopathological evaluation and then using latent class modeling, we
      estimated the operating characteristics of these tests in the absence of a
      reference standard test. RESULTS: There was a weak inter-rater agreement (kappa <
      0.15) as well as a weak intra-rater reproducibility (Pearson's r = 0.28, intra
      class correlation rho = 0.03) in the histopathological evaluation of potentially
      high-risk precancerous lesions. When compared to histopathology,
      chemiluminescence and toluidine blue retention had a sensitivity of 1.00 and
      0.59, respectively and a specificity of 0.01 and 0.79, respectively. However,
      latent class analysis indicated a low sensitivity (0.37) and high specificity
      (0.90) of histopathological evaluation. Toluidine blue had a near perfect high
      sensitivity and specificity for detection of high-risk lesions. CONCLUSION: In
      our study, there was variability in the histopathological evaluation of oral
      precancerous lesions. Our results indicate that toluidine blue retention test may
      be better suited than chemiluminescence to detect high-risk oral precancerous
      lesions in a high-prevalence and low-resource setting like India.

PMID- 22410296
TI  - Development of decay energy spectroscopy using low temperature detectors.
AB  - We have developed a high-resolution detection technique for measuring the energy
      and activity of alpha decay events using low-temperature detectors. A small
      amount of source material containing alpha-emitting radionuclides was enclosed in
      a 4pi metal absorber. The energy of the alpha particles as well as that of the
      recoiled nuclides, low-energy electrons, and low-energy x-rays and gamma-rays was
      converted into thermal energy of the gold absorber. A metallic magnetic
      calorimeter serving as a fast and sensitive thermometer was thermally attached to
      the metal absorber. In the present report, experimental demonstrations of Q
      spectroscopy were made with a new meander-type magnetic calorimeter. The thermal
      connection between the temperature sensor and the absorber was established with
      annealed gold wires. Each alpha decay event in the absorber resulted in a
      temperature increase of the absorber and the temperature sensor. Using the
      spectrum measured for a drop of (226)Ra solution in a 4pi gold absorber, all of
      the alpha emitters in the sample were identified with a demonstration of good
      detector linearity. The resolution of the (226)Ra spectrum showed a 3.3 keV FWHM
      at its Q value together with an expected gamma escape peak at the energy shifted
      by its gamma-ray energy.

PMID- 22410297
TI  - Investigations on TDCR measurements with the HIDEX 300 SL using a free parameter
      model.
AB  - The Triple to Double Coincidence Ratio (TDCR) method requires a special counting
      system with three photodetectors. The systems currently used by National
      Metrology Institutes for activity standardizations are custom built, and up to
      now the HIDEX 300 SL counter is the only TDCR counter commercially available. At
      PTB, measurements with a special metrology version of this counter were carried
      out to investigate its applicability for activity standardizations. The activity
      results of measurements with the HIDEX counter are compared to those obtained
      with a PTB-TDCR counter, as such a comparison reduces the model dependence. In
      addition, a spectrometry method was applied to measure (109)Cd samples and a new
      TDCR-Cerenkov method was tested with (32)P samples.

PMID- 22410298
TI  - Coincidence summing corrections applied to volume sources.
AB  - The numerical calculation of coincidence summing corrections requires both the
      total and full-energy peak efficiencies to be included in the corrective factors.
      Moreover, in the case of volume sources, the coincidence probability depends on
      the position of the photon emission inside the radioactive sample, thus it is
      necessary to calculate the coincidence summing corrective factors by integrating
      the elemental contributions for the entire volume. The software ETNA calculates
      coincidence summing corrective factors according to a deterministic method, for
      volume sources, two approaches are included in the software: the "simplified"
      calculation uses directly the efficiency of the volume source like in the case of
      point source, and the "complete" calculation performs the volume integration. To
      assess the difference between these, different geometrical cases are tested for
      several radionuclides using both methods.

PMID- 22410299
TI  - SiC surface orientation and Si loss rate effects on epitaxial graphene.
AB  - We have explored the properties of SiC-based epitaxial graphene grown in a cold
      wall UHV chamber. The effects of the SiC surface orientation and silicon loss
      rate were investigated by comparing the characteristics of each formed graphene.
      Graphene was grown by thermal decomposition on both the silicon (0001) and carbon
      (000-1) faces of on-axis semi-insulating 6H-SiC with a "face-down" and "face-up"
      orientations. The thermal gradient, in relation to the silicon flux from the
      surface, was towards the surface and away from the surface, respectively, in the
      two configurations. Raman results indicate the disorder characteristics
      represented by ID/IG down to < 0.02 in Si-face samples and < 0.05 in C-faces over
      the 1 cm2 wafer surface grown at 1,450 degrees C. AFM examination shows a better
      morphology in face-down surfaces. This study suggests that the optimum
      configuration slows the thermal decomposition and allows the graphene to form
      near the equilibrium. The Si-face-down orientation (in opposition to the
      temperature gradient) results in a better combination of low disorder ratio,
      ID/IG, and smooth surface morphology. Mobility of Si-face-down orientation has
      been measured as high as approximately 1,500 cm2/Vs at room temperature.
      Additionally, the field effect transistors have been fabricated on both Si-face
      down and C-face-down showing an ambipolar behavior with more favorable electron
      conduction.

PMID- 22410300
TI  - Surfactant preparations for tuberculosis and other diseases beyond infancy: a
      letter from Russia.

PMID- 22410301
TI  - Perylene dominates the organic contaminant profile in the Berau delta, East
      Kalimantan, Indonesia.
AB  - The geographical distributions of polyaromatic hydrocarbons (PAHs),
      polychlorinated biphenyls (PCBs), hexachlorobenzene, and 1,1-dichloro-2,2-bis(4
      chlorophenyl)ethene (4,4'-DDE) were studied in the Berau delta (East Kalimantan,
      Indonesia), using sediment sampling and passive water sampling with semipermeable
      membrane devices. High concentrations of perylene were observed in sediments (54
      580 ng g(-1) dry weight), and water (1-680 pg L(-1)). Perylene accounted for
      about 60% of the total concentrations of PAHs in the sediment. The relative
      abundance of the other PAHs was indicative of petrogenic sources. Concentrations
      of PCBs, hexachlorobenzene, and 4,4'-DDE in sediments were below or close to the
      detection limit (~ 0.02 ng g(-1)). The analysis of a sediment core revealed no
      appreciable changes in the concentration of target compounds over the past three
      decades. We show that sediment sampling and passive water sampling are
      complementary techniques, and propose to bring the results of both methods to the
      same concentration scale, using locally derived sediment-water partition
      coefficients.

PMID- 22410302
TI  - Prevalence and trends of hepatitis C virus among blood donors in Antananarivo,
      from 2003 to 2009.
AB  - PURPOSE OF THE STUDY: Due to anemia and maternal, childhood and infancy diseases,
      blood transfusion is one of the most important medical cares given in sub-Saharan
      Africa, including Madagascar. World Health Organization encourages worldwide
      countries to maximize transfusion security. Until now, there was no data within a
      large population of blood donors. Therefore, the aim of this study was to assess
      the prevalence and time trends of hepatitis C virus (HCV) among all first-time
      blood donors coming into the National Centre of Transfusion Supply in
      Antananarivo. MATERIAL AND METHODS: This retrospective study was conducted at the
      National Centre of Transfusion Supply in Antananarivo from 2003 to May 2009. We
      looked up to all recorded results of systematic screening of blood donor
      candidates and we took data about all first-time blood donors, including age and
      gender. Forty-seven thousand five hundred and ten of 47,636 first-time blood
      donors were retained, the others were excluded due to lack of some data. RESULTS:
      The mean age of our donors was 33.3 years (35.8 for male, and 32.6 for female;
      P<<0.05). Eighty percent were male (38,225/47,510). HCV prevalence was 0.65%
      during the period of study and HCV positive donor candidates were older than HCV
      negative (mean age: 39.1 vs. 33.2; P<<0.05). It was in fact stable from 2003 to
      2007, and then decreased. HCV prevalence was higher in women than in men (0.9 vs.
      0.6; P<0.05), and it increased by age (P<0.05). CONCLUSION: Our study found a low
      prevalence of HCV among blood donors compared to many countries in Africa.

PMID- 22410303
TI  - Serial soluble neurofilament heavy chain in plasma as a marker of brain injury
      after cardiac arrest.
AB  - INTRODUCTION: Induced hypothermia has been shown to improve outcome after cardiac
      arrest, but early prognostication is hampered by the need for sedation. Here we
      tested whether a biomarker for neurodegeneration, the neurofilament heavy chain
      (NfH), may improve diagnostic accuracy in the first days after cardiac arrest.
      METHODS: This prospective study included 90 consecutive patients treated with
      hypothermia after cardiac arrest. Plasma levels of phosphorylated NfH (SMI35)
      were quantified using standard ELISA over a period of 72 h after cardiac arrest.
      The primary outcome was the dichotomized Cerebral Performance Categories scale
      (CPC). A best CPC 1-2 during 6 months follow-up was considered a good outcome, a
      best CPC of 3-4 a poor outcome. Receiver operator characteristics and area under
      the curve were calculated. RESULTS: The median age of the patients was 65 years,
      and 63 (70%) were male. A cardiac aetiology was identified in 62 cases (69%). 77
      patients (86%) had out-of-hospital cardiac arrest. The outcome was good in 48 and
      poor in 42 patients. Plasma NfH levels were significantly higher 2 and 36 hours
      after cardiac arrest in patients with poor outcome (median 0.28 ng/mL and 0.5
      ng/mL, respectively) compared to those with good outcome (0 ng/mL, p = 0.016, p <
      0.005, respectively). The respective AUC were 0.72 and 0.71. CONCLUSIONS: Plasma
      NfH levels correlate to neurological prognosis following cardiac arrest. In this
      study, 15 patients had neurological co-morbidities and there was a considerable
      overlap of data. As such, neurofilament should not be used for routine
      neuroprognostication until more data are available.

PMID- 22410304
TI  - Effect of simulated gastro-duodenal digestion on the allergenic reactivity of
      beta-lactoglobulin.
AB  - BACKGROUND: Cow's milk (CM) allergy affects about 2% of infants. The
      allergenicity of dietary proteins, including those from CM, has been related to
      their digestibility although the generality of the link and its causality remains
      to be demonstrated. In this study we use an in vitro digestion system, to
      investigate the digestibility of beta-lactoglobulin (blg) during gastrointestinal
      transit and to assess the impact of this process on blg allergenic reactivity in
      CM allergic children. METHODS: Blg digesta were prepared using an in vitro
      digestion protocol simulating either gastric digestion alone or followed by
      duodenal digestion with or without phosphatidylcholine (PC). Biochemical analysis
      of blg digesta was performed by SDS-PAGE and their concentration was measured by
      a sandwich ELISA. Assessment of their allergenic reactivity was done in vitro by
      EAST inhibition, specific basophil activation (basotest) and lymphocyte
      proliferation (PCNA-flow cytometry) assays using sera and cells from patients
      allergic to blg and in vivo by skin prick testing (SPT) of these patients.
      RESULTS: Blg was only broken down to smaller peptides after gastro-duodenal
      digestion although a sizeable amount of intact protein still remained. Digestion
      did not modify the IgE binding capacity of blg except for gastro-duodenal
      digestion performed in the absence of PC. These results are consistent with the
      quantity of intact blg remaining in the digesta. Overall both gastric and
      gastroduodenal digestion enhanced activation of sensitized basophils and
      proliferation of sensitized lymphocytes by blg. However, there was a tendency
      towards reduction in mean diameter of SPT following digestion, the PC alone
      during phase 1 digestion causing a significant increase in mean diameter.
      CONCLUSIONS: Digestion did not reduce the allergenic reactivity of blg to a
      clinically insignificant extent, PC inhibiting digestion and thereby protecting
      blg allergenic reactivity. SPT reactivity was reduced compared to blg
      immunoreactivity in in vitro tests.

PMID- 22410305
TI  - Antiplatelet therapy for patients with diabetes mellitus and acute coronary
      syndrome.
AB  - In diabetes mellitus, platelet hyperreactivity is common and may contribute to
      the high incidence of cardiovascular disease; dual antiplatelet therapy reduces
      the risk of recurrence. Prasugrel or ticagrelor provides a greater, more
      consistent antiplatelet effect than clopidogrel. Prasugrel provides greater
      clinical benefit than clopidogrel in patients with diabetes (hazard ratio [HR],
      0.70; P<0.001) versus those without diabetes (HR, 0.86; P=0.02), due to greater
      reductions in cardiovascular events and no increased major bleeding. Similar
      clinical benefits are seen with ticagrelor versus clopidogrel in patients with
      and without diabetes. Evidence suggests that prasugrel/aspirin may provide
      particular advantages for patients with diabetes mellitus.

PMID- 22410306
TI  - K+ pump: from caterpillar midgut to human cochlea.
AB  - Deafness is a serious condition that affects millions of people and can also lead
      to dementia. Moreover, Karet and associates reported in 1999 that mutations in
      the gene encoding H(+) V-ATPase subunit B(1) lead to deafness. Yet ionic flows
      that enable humans to hear high-pitched sounds at 20,000 cycles/sec (20 kHz) are
      not well understood. Sound is transduced to electrical signals by stereocilia of
      hair cells by influx of Ca(2+) and K(+) as the "transducer channel" opens
      transiently and reduces the ~90 mV (endolymph positive) endocochlear potential
      (EP) by ~20 mV as the receptor potential. The EP as well as concentrations of
      Ca(2+), H(+) and K(+) must remain constant to produce reliable signals. Ca(2+)
      entry is balanced by Ca(2+) exit via a plasma membrane Ca(2+) ATPase (PMCA2a) but
      the Ca(2+) exit is coupled to H(+) entry. Moreover, K(+) entry is balanced by
      K(+) exit via a long diffusion route through several channels which is too slow
      to account for 20 kHz signaling. The problem is solved by a new hypothesis in
      which an H(+) V-ATPase generates the EP and removes the H(+) while a new
      K(+)/H(+) antiporter uses the voltage to drive H(+) back in and the K(+) back
      out. In the new model, Ca(2+), H(+) and K(+) cycle between unstirred layers on
      the endolymph- and cytoplasmic- borders of the stereocilial membrane through
      distances of ~20 nanometers with travel time of ~10 MUs, which is fast enough to
      account for the 50 MUs open/close time for 20 kHz signaling. Central to this
      model is the hypothesis that a K(+) pump which secretes K(+) into a K(+)-rich
      compartment is composed of a voltage producing (electrogenic) H(+) V-ATPase that
      is electrically coupled to a voltage-driven (electrophoretic) K(+)/nH(+)
      antiporter (KHA). Conversely, for an H(+) V-ATPase to secrete K(+) into a K(+)
      rich compartment, it must be coupled to a KHA. Richard Keynes reviewed evidence
      in 1969 that such a K(+) pump, which he called a Type V pump, is present in the
      stria vascularis of cochlea and the goblet cell apical membrane of caterpillars.
      Its signature is a large outside positive potential of ~100 mV, K(+) secretion
      into a K(+) rich compartment and reversible inhibition by anoxia. The key role of
      the Type V K(+) pump in generating the EP was recognized by Sellick and Bock in
      1974 and others but has disappeared from the hearing literature during the past
      decades. Its revival here is based on immunolocalization of KHA2 in the
      stereocilial membrane and Gillespie's generously shared mass spectroscopy
      evidence that all but one of the V(1) ATPase subunits are detected in isolated
      chicken stereocilia but V(o) and KHAs are not detected (implying that KHAs must
      be in the membrane). The new model proposed in the present paper could lead to
      important changes in our understanding of sensory physiology.

PMID- 22410307
TI  - Electrophysiological correlates of processing facial attractiveness and its
      influence on cooperative behavior.
AB  - The present study investigated the temporal features of processing facial
      attractiveness, and its influence on the subsequent cooperative behavior. Event
      related potentials (ERPs) were recorded for both face stimuli (attractive or
      unattractive faces) and feedback stimuli (loss or gain) while participants
      performed a modified trust game task, in which participants decided whether to
      cooperate with fictional partners (attractive or unattractive faces) for a chance
      to earn monetary rewards; feedback (loss or gain) were presented after their
      decisions. The behavioral results showed that participants were more likely to
      cooperate with the attractive partners than with the unattractive partners. The
      ERP analysis for face stimuli showed that a smaller P2 amplitude was elicited by
      attractive faces compared to unattractive faces. In addition, attractive faces
      elicited larger N2 and smaller late positive component (LPC) amplitudes than
      unattractive faces. More interestingly, a larger feedback related negativity
      (FRN) was elicited within the attractive face condition compared with the
      unattractive face condition. Therefore, our findings demonstrate that the
      discrimination of attractive and unattractive faces occurs at the early P2 stage,
      reflecting automatic processing of facial attractiveness. Moreover, the present
      study further demonstrates that facial attractiveness facilitates cooperative
      behavior, and that FRN elicited by outcome stimuli might be used as an index of
      how people judge and predict another's behavior in a social game.

PMID- 22410308
TI  - Genetic characterization of Leptospira spp. from beavers found dead in south-west
      Germany.

PMID- 22410309
TI  - An investigation of a recent outbreak of nocardioform placentitis caused
      abortions in horses.
AB  - Nocardioform placentitis associated with gram positive branching actinomycetes
      caused a record number of abortions in mares diagnosed by the University of
      Kentucky Veterinary Diagnostic Laboratory (UKVDL) affecting the 2011 foal crop
      (2011 foal crop: the cohort of foals conceived during the 2010 breeding season).
      The goal of the present study is to make a comprehensive analysis of this
      outbreak in terms of frequencies of the bacteria causing nocardioform placentitis
      mediated abortions and to investigate the ages of fetuses, abortion months and
      breeding times. In the present study, characteristic slow-growing, pungent/soil
      odor gram positive branching actinomycetes were recovered in high numbers in
      placental specimens in 76 abortion cases diagnosed as nocardioform placentitis by
      pathologists. To determine the type of actinomycetes responsible for the
      abortions, PCR assays were performed on the gram positive branching bacilli. The
      most prominent actinomycetes species were Amycolatopsis spp. (37 cases, 48.7%)
      and Crossiella equi (C. equi) (22 cases, 28.9%). Six cases (7.9%) contained both
      Amycolatopsis spp., and C. equi. 10 isolates were unidentified by PCR assays and
      shown to have high DNA sequence homology to Streptomyces species, Microbacterium
      species, Nocardia species and Allokutzneria species, as evidenced by 16 rRNA gene
      sequencing and phylogenetic analysis. Nocardioform placentitis related abortions
      occurred mostly between December 2010 and April 2011 happening exclusively in the
      last trimester. Breeding time of aborted pregnancies ranged from March 2010 to
      July 2010, suggesting that if transmission of the actinomycetes agents occurred
      during breeding, it was not related to a specific season.

PMID- 22410310
TI  - Chronic laminitis is associated with potential bacterial pathogens in the
      laminae.
AB  - A common sequella of chronic laminitis in horses is repeated abscesses with
      variable lameness and drainage. It is unclear whether the exudate represents the
      debridement phase of a non-septic inflammatory process involving clearance of
      laminar tissue damaged during the acute episode of laminitis, or a response to a
      microbial infection developed by ascent of microbes from the environment to the
      tissue via the white line. The objective of this study was to evaluate the
      possibility that an undiagnosed microbial infection in laminar tissue is present
      in laminar tissue collected from chronically laminitic horses without an active
      hoof abscess. Methods to collect laminar tissue, aseptically, from control (non
      laminitic) horses and those with chronic/recurrent laminitis are described.
      Laminae homogenates were evaluated for the presence of bacteria. Bacteria were
      identified using biochemical tests and sequencing of 16S rRNA and virulence
      genes. Laminae from chronically laminitic horses revealed 100-fold higher levels
      (P=0.002) of bacteria compared to control, non-laminitic horses. Although
      environmental organisms were identified, potential pathogens were identified.
      Included were Gram positive bacteria, Brevibacterium luteolum, coagulase-negative
      Staphylococcus spp. as well as Gram negative bacteria, enterohemorrhagic
      Escherichia coli and Alcaligenes faecalis. Further research is warranted to
      evaluate the role of bacteria in equine chronic laminitis.

PMID- 22410311
TI  - The utility and sensitivity of colour Doppler ultrasound in monitoring changes in
      giant cell arteritis.
AB  - OBJECTIVES: To explore the sensitivity to change of colour Doppler ultrasound
      (CDUS) in giant cell arteritis (GCA). METHODS: This was a blind, prospective
      study composed of 30 consecutive patients diagnosed with GCA. In 25 of the cases
      this was their first episode of GCA, and 13 of the cases were relapses. All
      participants had presented with at least 1 branch involvement in the basal
      sonography, and steroid treatment had been initiated. A CDUS was performed every
      2 weeks during the first month, and every 4 weeks thereafter, until halo
      disappearance was observed in the bilateral parietal and frontal branches of the
      temporal superficial artery. RESULTS: Thirty-eight episodes of GCA in 30
      different patients (19 women and 11 men; mean age, 79.24+/-4.76 years; range 70
      88) were followed. Dark halo disappearance occurred in 95% of cases. The mean
      time until halo disappearance was observed was around 11 weeks, with 50% of cases
      showing halo disappearance within the first 8 weeks. The relapse cases appeared
      to have less arterial wall affectation than the primary GCA cases, reduced
      erythrocyte sedimentation rate ESR and an earlier loss of the halo sign. Patients
      with a smaller number of affected branches required less time for halo
      disappearance. CONCLUSIONS: CDUS shows a sensitivita to change in GCA. Halo
      disappearance is rare before two weeks, and it frequently persists during the
      first two months after initiating steroid therapy. Our data emphasise the
      advantages of using CDUS to monitor GCA activity.

PMID- 22410312
TI  - Effectiveness and safety of 30 mg versus 40 mg stavudine regimens: a cohort study
      among HIV-infected adults initiating HAART in South Africa.
AB  - BACKGROUND: As stavudine remains an important and widely prescribed drug in
      resource-limited settings, the effect of a reduced dose of stavudine (from 40 mg
      to 30 mg) on outcomes of highly active antiretroviral therapy (HAART) remains an
      important public health question. METHODS: We analyzed prospectively collected
      data from the Themba Lethu Clinic in Johannesburg, South Africa. We assessed the
      relationship between stavudine dose and six- and/or 12-month outcomes of
      stavudine substitution, failure to suppress viral load to below 400 copies/ml,
      development of peripheral neuropathy, lipoatrophy and hyperlactatemia/lactic
      acidosis. Since individuals with a baseline weight of less than 60 kg were
      expected to have received the same dose of stavudine throughout the study period,
      analysis was restricted to individuals who weighed 60 kg or more at baseline.
      Data were analyzed using logistic regression. RESULTS: Between 1 April 2004 and
      30 September 2009, 3910 patients were initiated on antiretroviral therapy (ART)
      with a recorded stavudine dose and were included in the analysis. Of these, 2445
      (62.5%) received a 40 mg stavudine dose while 1565 (37.5%) received 30 mg. In
      multivariate analysis, patients receiving a 40 mg dose were more likely to
      discontinue stavudine use (adjusted odds ratio, OR 1.71; 95% confidence limits,
      CI 1.13-2.57) than those receiving 30 mg by 12 months on ART. Additionally,
      patients receiving 40 mg doses of stavudine were more likely to report peripheral
      neuropathy (OR 3.12; 95% CI 1.86-5.25), lipoatrophy (OR 11.8; 95% CI 3.2-43.8)
      and hyperlactatemia/lactic acidosis (OR 8.37; 95% CI 3.83-18.29) in the same time
      period. Failure to suppress HIV viral load within 12 months of HAART initiation
      was somewhat more common among those given 40 mg doses (OR 1.62; 95% CI 0.88,
      2.97) although this result lacked precision. Sensitivity analyses accounting for
      death and loss to follow up generally supported these estimates. CONCLUSIONS:
      Lower stavudine dosage is associated with fewer reports of several stavudine
      associated adverse events and also a lower risk of stavudine discontinuation
      within the first year on ART.

PMID- 22410313
TI  - The 'Mandarin-missionary' strategy: Robert Kennicott, Spencer Fullerton Baird and
      specimen collection in the Hudson's Bay Territory.
AB  - In 1859, Robert Kennicott, one of the most promising specimen collectors and
      young naturalists in the United States, was dispatched to Hudson's Bay Territory
      by Spencer Fullerton Baird, the Assistant Secretary of the Smithsonian. Kennicott
      was chosen because of previous experience in Canada, the familiarity with biota
      of the American Midwest, and because he had a boundless, infectious, enthusiasm
      for natural history that was typical among Baird's closest protegees. Kennicott
      was a natural scientific envoy--or missionary--to the officers of the Hudson's
      Bay Company, and many officers were enthusiastically 'converted' to the cause of
      collecting and/or overseeing the collection of natural history specimens. Due to
      this collaboration between Baird, Kennicott and the officers of the Hudson's Bay
      Company, the Smithsonian became a leading center of Canadian natural history in
      the Western hemisphere.

PMID- 22410314
TI  - Ring distributions leading to species formation: a global topographic analysis of
      geographic barriers associated with ring species.
AB  - BACKGROUND: In the mid 20th century, Ernst Mayr and Theodosius Dobzhansky
      championed the significance of circular overlaps or ring species as the perfect
      demonstration of speciation, yet in the over 50 years since, only a handful of
      such taxa are known. We developed a topographic model to evaluate whether the
      geographic barriers that favor processes leading to ring species are common or
      rare, and to predict where other candidate ring barriers might be found. RESULTS:
      Of the 952,147 geographic barriers identified on the planet, only about 1% are
      topographically similar to barriers associated with known ring taxa, with most of
      the likely candidates occurring in under-studied parts of the world (for example,
      marine environments, tropical latitudes). Predicted barriers separate into two
      distinct categories: (i) single cohesive barriers (< 50,000 km2), associated with
      taxa that differentiate at smaller spatial scales (salamander: Ensatina
      eschscholtzii; tree: Acacia karroo); and (ii) composite barriers - formed by
      groups of barriers (each 184,000 to 1.7 million km2) in close geographic
      proximity (totaling 1.9 to 2.3 million km2) - associated with taxa that
      differentiate at larger spatial scales (birds: Phylloscopus trochiloides and
      Larus (sp. argentatus and fuscus)). When evaluated globally, we find a large
      number of cohesive barriers that are topographically similar to those associated
      with known ring taxa. Yet, compared to cohesive barriers, an order of magnitude
      fewer composite barriers are similar to those that favor ring divergence in
      species with higher dispersal. CONCLUSIONS: While these findings confirm that the
      topographic conditions that favor evolutionary processes leading to ring
      speciation are, in fact, rare, they also suggest that many understudied natural
      systems could provide valuable demonstrations of continuous divergence towards
      the formation of new species. Distinct advantages of the model are that it (i)
      requires no a priori information on the relative importance of features that
      define barriers, (ii) can be replicated using any kind of continuously
      distributed environmental variable, and (iii) generates spatially explicit
      hypotheses of geographic species formation. The methods developed here - combined
      with study of the geographical ecology and genetics of taxa in their environments
      - should enable recognition of ring species phenomena throughout the world.

PMID- 22410315
TI  - Carbamylated erythropoietin ameliorates cyclosporine nephropathy without
      stimulating erythropoiesis.
AB  - The introduction of cyclosporine (CsA) has improved graft survival, but it causes
      nephropathy, which limits its clinical utility. Recently, we reported that
      carbamylated erythropoietin (CEPO) protected kidneys from ischemia reperfusion
      injury as well as EPO. To investigate the clinical  applications of CEPO, we next
      evaluated the long-term therapeutic effect of CEPO using a CsA-induced
      nephropathy model. CsA caused renal dysfunction, while EPO/CEPO administration
      significantly improved renal function. EPO treatment significantly increased Hb
      concentration, while CEPO treatment  neither enhanced nor reduced Hb
      concentration. CsA treatment induced tubular apoptosis, while EPO/CEPO
      administration inhibited it and increased PI3 kinase activation and Akt
      phosphorylation. In parallel, morphological assessment revealed that EPO/CEPO
      significantly reduced CsA-induced interstitial  fibrosis and inhibited
      interstitial macrophage infiltration. In addition, real-time RT-PCR demonstrated
      that cortical mRNA levels of TGF-beta1 and type I collagen were suppressed in the
      EPO/CEPO group. These results suggest a new therapeutic approach using CEPO to
      protect kidneys from CsA-induced  nephropathy.

PMID- 22410316
TI  - Reduced expression of haloperidol conditioned catalepsy in rats by the dopamine
      D3 receptor antagonists nafadotride and NGB 2904.
AB  - Haloperidol, a dopamine (DA) D2 receptor-preferring antagonist, produces
      catalepsy whereby animals maintain awkward posture for a period of time. Sub
      threshold doses of haloperidol fail to produce catalepsy initially, however, when
      the drug is given repeatedly in the same test environment, gradual day-to-day
      increases in catalepsy are observed. More importantly, if sensitized rats are
      injected with saline instead of haloperidol they continue to be cataleptic in the
      test environment suggesting that environment-drug associations may play a role.
      DA D3 receptors have been implicated in a number of conditioned behaviors. We
      were interested if DA D3 receptors contribute to catalepsy sensitization and
      conditioning in rats. We tested this hypothesis using the DA D3 receptor
      selective antagonist NGB 2904 (0.5, 1.8 mg/kg) and the DA D3 receptor-preferring
      antagonist nafadotride (0.1, 0.5 mg/kg). For 10 consecutive conditioning days
      rats were treated with one of the D3 receptor antagonists alone or in combination
      with haloperidol (0.25 mg/kg) and tested for catalepsy, quantified by the time a
      rat remained with its forepaws on a horizontal bar. On test day (day 11), rats
      were injected with saline or the D3 receptor antagonist and tested for
      conditioned catalepsy in the previously drug-paired environment. Rats treated
      with NGB 2904 or nafadotride alone did not develop catalepsy. Rats treated with
      haloperidol or haloperidol plus NGB 2904 or nafadotride developed catalepsy
      sensitization with repeated conditioning. When injected with saline they
      continued to exhibit catalepsy in the test environment--now conditioned. On the
      other hand, NGB 2904 (1.8 mg/kg) or nafadotride (0.5 mg/kg) given on the test day
      (after sensitization to haloperidol) significantly attenuated the expression of
      conditioned catalepsy. Our data suggest that the D3 receptor antagonist NGB 2904
      (1.8 mg/kg) and nafadotride (0.5 mg/kg) significantly attenuate conditioned
      catalepsy in rats when given in test but not when given during sensitization.
      Results implicate DA D3 receptors in regulating the expression of conditioned
      catalepsy.

PMID- 22410317
TI  - Synthetic and semi-synthetic chondroitin sulfate oligosaccharides,
      polysaccharides, and glycomimetics.
AB  - Chondroitin sulfate (CS) is a sulfated polysaccharide involved in a myriad of
      biological processes. Due to the variable sulfation pattern of CS polymer chains,
      the need to study in detail structure-activity relationships regarding CS
      biomedical features has provoked much interest in obtaining synthetic CS species.
      This paper reviews two decades of synthetic and semi-synthetic CS
      oligosaccharides, polysaccharides, and glycomimetics obtained by chemical,
      chemoenzymatic, enzymatic, and microbiological-chemical strategies.

PMID- 22410318
TI  - Understanding theoretically the impact of reporting of disease cases in
      epidemiology.
AB  - In conducting preliminary analysis during an epidemic, data on reported disease
      cases offer key information in guiding the direction to the in-depth analysis.
      Models for growth and transmission dynamics are heavily dependent on preliminary
      analysis results. When a particular disease case is reported more than once or
      alternatively is never reported or detected in the population, then in such a
      situation, there is a possibility of existence of multiple reporting or under
      reporting in the population. In this work, a theoretical approach for studying
      reporting error in epidemiology is explored. The upper bound for the error that
      arises due to multiple reporting is higher than that which arises due to under
      reporting. Numerical examples are provided to support the arguments. This paper
      mainly treats reporting error as deterministic and one can explore a stochastic
      model for the same.

PMID- 22410319
TI  - Streptavidin suppresses T cell activation and inhibits IL-2 production and CD25
      expression.
AB  - Streptavidin is widely used as a detection tool in biology research because of
      its high affinity and specificity binding to biotin. Biotin-streptavidin system
      has also been explored for detection of infection and tumor in clinical medicine.
      Here, we show immunosuppressive property of streptavidin on T cell activation and
      proliferation. Upon CD3 and CD28 stimulation, CD4(+) T cells produce interleukin
      2 (IL-2) and express IL-2 receptor alpha chain (CD25). Addition of streptavidin
      in T cell culture suppressed IL-2 synthesis and CD25 expression with no
      cytotoxicity. The immunosuppressive effect of streptavidin was reversed by
      excessive biotin. Conjugated to a single chain anti-CD7 variable fragment
      (scFvCD7), streptavidin was directly delivered to T cells and showed
      substantially more profound suppressive effect on T cell activation. These
      results suggest that streptavidin could potentially be used as a novel
      immunomodulator.

PMID- 22410320
TI  - Synthesis and crystal structure of hydroxyacetophenone Schiff bases containing
      propargyl moiety: solvent effects on UV-visible spectra.
AB  - Four tetradentate (N(2)O(2)) and tridentate (NO(2)) Schiff base compounds (L1-L4)
      with propargyl moiety were prepared by the condensation of 1-[2-hydroxy-4-(prop-2
      yn-1-yloxy)phenyl]ethanone with various aliphatic amines. The newly synthesized
      compounds (L1-L4) were characterized on the basis of the results of elemental
      analysis, thermal analysis, FT-IR, (1)H NMR spectroscopic studies and single
      crystal X-ray crystallography. The different bands observed in the electronic
      spectra of the compounds in various organic solvents have been assigned to the
      proper electronic transitions. The hydrogen bonding and tautomeric equilibria in
      both of solution and the solid state are explained. The solvatochromism of the
      synthesized compounds in different solvents in the UV-visible spectra are
      discussed.

PMID- 22410321
TI  - Extrapolatable analytical functions for tendon excursions and moment arms from
      sparse datasets.
AB  - Computationally efficient modeling of complex neuromuscular systems for dynamics
      and control simulations often requires accurate analytical expressions for moment
      arms over the entire range of motion. Conventionally, polynomial expressions are
      regressed from experimental data. But these polynomial regressions can fail to
      extrapolate, may require large datasets to train, are not robust to noise, and
      often have numerous free parameters. We present a novel method that
      simultaneously estimates both the form and parameter values of arbitrary
      analytical expressions for tendon excursions and moment arms over the entire
      range of motion from sparse datasets. This symbolic regression method based on
      genetic programming has been shown to find the appropriate form of mathematical
      expressions that capture the physics of mechanical systems. We demonstrate this
      method by applying it to 1) experimental data from a physical tendon-driven
      robotic system with arbitrarily routed multiarticular tendons and 2) synthetic
      data from musculoskeletal models. We show it outperforms polynomial regressions
      in the amount of training data, ability to extrapolate, robustness to noise, and
      representation containing fewer parameters--all critical to realistic and
      efficient computational modeling of complex musculoskeletal systems.

PMID- 22410322
TI  - Wavelet-based localization of oscillatory sources from magnetoencephalography
      data.
AB  - Transient brain oscillatory activities recorded with Eelectroencephalography
      (EEG) or magnetoencephalography (MEG) are characteristic features in
      physiological and pathological processes. This study is aimed at describing,
      evaluating, and illustrating with clinical data a new method for localizing the
      sources of oscillatory cortical activity recorded by MEG. The method combines
      time-frequency representation and an entropic regularization technique in a
      common framework, assuming that brain activity is sparse in time and space.
      Spatial sparsity relies on the assumption that brain activity is organized among
      cortical parcels. Sparsity in time is achieved by transposing the inverse problem
      in the wavelet representation, for both data and sources. We propose an estimator
      of the wavelet coefficients of the sources based on the maximum entropy on the
      mean (MEM) principle. The full dynamics of the sources is obtained from the
      inverse wavelet transform, and principal component analysis of the reconstructed
      time courses is applied to extract oscillatory components. This methodology is
      evaluated using realistic simulations of single-trial signals, combining fast and
      sudden discharges (spike) along with bursts of oscillating activity. The method
      is finally illustrated with a clinical application using MEG data acquired on a
      patient with a right orbitofrontal epilepsy. 

PMID- 22410323
TI  - Modeling the field distribution in deep brain stimulation: the influence of
      anisotropy of brain tissue.
AB  - The neurosurgical method of deep brain stimulation (DBS) is used to treat
      symptoms of movement disorders like Parkinson's disease by implanting stimulation
      electrodes in deep brain areas. The aim of this study was to examine the field
      distribution in DBS and the role of heterogeneous and anisotropic material
      properties in the brain areas where stimulation is applied. Finite element models
      of the human brain were developed comprising tissue heterogeneity and anisotropy.
      The tissue data were derived from averaged magnetic resonance imaging and
      diffusion tensor imaging datasets. Unilateral stimulation of the subthalamic
      nucleus (STN) was computed using an accurate model of an electrode used in
      clinical treatment of DBS extended with an encapsulation layer around the
      electrode body. Computations of anisotropic and isotropic brain models, which
      consider resistive tissue properties for unipolar and bipolar electrode
      configurations, were carried out. Electrode position was varied within an area
      around the stimulation center. Results have shown a deviation of 2% between
      anisotropic and isotropic field distributions in the vicinity of the STN. The
      sensitivity of this deviation referring to the electrode position remained small,
      but increased when the electrode position approached areas of high anisotropy.

PMID- 22410324
TI  - CNT/PDMS composite flexible dry electrodes for long-term ECG monitoring.
AB  - We fabricated a carbon nanotube (CNT)/ polydimethylsiloxane (PDMS) composite
      based dry ECG electrode that can be readily connected to conventional ECG
      devices, and showed its long-term wearable monitoring capability and robustness
      to motion and sweat. While the dispersion of CNTs in PDMS is challenging, we
      optimized the process to disperse untreated CNTs within PDMS by mechanical force
      only. The electrical and mechanical characteristics of the CNT/PDMS electrode
      were tested according to the concentration of CNTs and its thickness. The
      performances of ECG electrodes were evaluated by using 36 types of electrodes
      which were fabricated with different concentrations of CNTs, and with a differing
      diameter and thickness. The ECG signals were obtained by using electrodes of
      diverse sizes to observe the effects of motion and sweat, and the proposed
      electrode was shown to be robust to both factors. The CNT concentration and
      diameter of the electrodes were critical parameters in obtaining high-quality ECG
      signals. The electrode was shown to be biocompatible from the cytotoxicity test.
      A seven-day continuous wearability test showed that the quality of the ECG signal
      did not degrade over time, and skin reactions such as itching or erythema were
      not observed. This electrode could be used for the long-term measurement of other
      electrical biosignals for ubiquitous health monitoring including EMG, EEG, and
      ERG.

PMID- 22410325
TI  - Bayesian hemodynamic parameter estimation by bolus tracking perfusion weighted
      imaging.
AB  - A delay-insensitive probabilistic method for estimating hemodynamic parameters,
      delays, theoretical residue functions, and concentration time curves by computed
      tomography (CT) and magnetic resonance (MR) perfusion weighted imaging is
      presented. Only a mild stationarity hypothesis is made beyond the standard
      perfusion model. New microvascular parameters with simple hemodynamic
      interpretation are naturally introduced. Simulations on standard digital phantoms
      show that the method outperforms the oscillating singular value decomposition
      (oSVD) method in terms of goodness-of-fit, linearity, statistical and systematic
      errors on all parameters, especially at low signal-to-noise ratios (SNRs). Delay
      is always estimated sharply with user-supplied resolution and is purely arterial,
      by contrast to oSVD time-to-maximum TMAX that is very noisy and biased by mean
      transit time (MTT), blood volume, and SNR. Residue functions and signals
      estimates do not suffer overfitting anymore. One CT acute stroke case confirms
      simulation results and highlights the ability of the method to reliably estimate
      MTT when SNR is low. Delays look promising for delineating the arterial occlusion
      territory and collateral circulation.

PMID- 22410326
TI  - Comparison of list-mode and DIRECT approaches for time-of-flight PET
      reconstruction.
AB  - Early clinical results with time-of-flight (TOF) positron emission tomography
      (PET) systems have demonstrated the advantages of TOF information in PET
      reconstruction. Reconstruction approaches in TOF-PET systems include list-mode
      and binned iterative algorithms as well as confidence-weighted analytic methods.
      List-mode iterative TOF reconstruction retains the resolutions of the data in the
      spatial and temporal domains without any binning approximations but is
      computationally intensive. We have developed an approach [DIRECT (direct image
      reconstruction for TOF)] to speed up TOF-PET reconstruction that takes advantage
      of the reduced angular sampling requirement of TOF data by grouping list-mode
      data into a small number of azimuthal views and co-polar tilts and depositing the
      grouped events into histo-images, arrays with the sampling and geometry of the
      final image. All physical effects are included in the system model and deposited
      in the same histo-image structure. Using histo-images allows efficient
      computation during reconstruction without ray-tracing or interpolation
      operations. The DIRECT approach was compared with 3-D list-mode TOF ordered
      subsets expectation maximization (OSEM) reconstruction for phantom and patient
      data taken on the University of Pennsylvania research LaBr (3) TOF-PET scanner.
      The total processing and reconstruction time for these studies with DIRECT
      without attention to code optimization is approximately 25%-30% that of list-mode
      TOF-OSEM to achieve comparable image quality. Furthermore, the reconstruction
      time for DIRECT is independent of the number of events and/or sizes of the
      spatial and TOF kernels, while the time for list-mode TOF-OSEM increases with
      more events or larger kernels. The DIRECT approach is able to reproduce the image
      quality of list-mode iterative TOF reconstruction both qualitatively and
      quantitatively in measured data with a reduced time.

PMID- 22410327
TI  - Predictors of invasive adenocarcinoma after conization for cervical
      adenocarcinoma in situ.
AB  - OBJECTIVE: Modified radical hysterectomy has been advocated for the definitive
      treatment of patients with cervical adenocarcinoma in situ (ACIS) with positive
      conization margins due to the risk of a co-existing invasive cervical
      adenocarcinoma (ICA). We sought to identify patients who can be safely managed
      with an extrafascial hysterectomy based on predictors of invasion in the
      conization specimen. METHODS: Between 1996 and 2010, we identified 33 patients
      who had definitive surgical management for cervical ACIS following conization
      with positive margins and/or positive endocervical curettage (ECC). Demographic
      and pathologic characteristics were collected by chart review. Statistical
      analysis was performed using Fisher's exact test. RESULTS: Among 33 patients, 4
      (12%) had ICA in the hysterectomy specimen. Predictors of ICA included pathologic
      suspicion of invasion (PSI) in the conization specimen and positive ECC. In
      patients with ICA at hysterectomy, PSI and ACIS-positive ECC were found in 75%
      (p=0.32) and 100% (p=0.09) respectively. When PSI was present and the ECC was
      positive, the positive predictive value (PPV) for ICA was 33% (2 of 6). When PSI
      was absent, the negative predictive value (NPV) for ICA was 94% (1 of 16). When
      both PSI and ECC were negative, the NPV for ICA was 100% (0 of 6). CONCLUSIONS:
      Women with cervical ACIS have the highest risk for ICA in the setting of positive
      cone margins, positive ECC, and presence of PSI in the conization specimen.
      Extrafascial hysterectomy remains a viable option for women with positive cone
      margins when ECC is negative and PSI is absent.

PMID- 22410328
TI  - Mucinous histology is a risk factor for nodal metastases in endometrial cancer.
AB  - OBJECTIVES: Mucinous adenocarcinoma of the endometrium (MUC) is a rare
      histological variant of endometrial carcinoma accounting for 1-9% of endometrioid
      tumors. Few studies have characterized its clinical behavior. This is a case
      control study at a single institution comparing the risk factors and clinical
      course of MUC relative to endometrioid adenocarcinoma. METHODS: A case-control
      study was performed including patients treated for endometrial cancer between
      1996 and 2006. 41 cases of mucinous adenocarcinoma were identified. Each case was
      matched with two controls of endometrioid histology by age and histological
      grade. Cases and controls were compared with regard to known risk factors for
      endometrial cancer and the extent of disease at diagnosis. Chi-square tests were
      used to compare proportions and Student's t-tests for the comparison of means.
      Multivariate regression was used to identify the independent predictors of lymph
      node metastases. Overall survival was calculated using the Kaplan-Meier method
      and compared with the Log-rank test. p<.05 was considered significant for all
      tests. RESULTS: Cases and controls were matched by age and FIGO grade and were
      found to be similar in regard to ethnicity, body mass index and medical history.
      No significant difference in myometrial invasion (MI)>50% or the presence of
      lymph-vascular space invasion was found between cases and controls, however, 17%
      of patients with MUC had lymph node metastases compared to 3% of controls
      (p=.01). Multivariate analysis controlling for both tumor grade and depth of MI
      identified mucinous histology as an independent predictor of lymph node
      metastasis (p=.02). There was no difference in adjuvant treatment, recurrence
      rate or survival between the two groups. CONCLUSION: Mucinous differentiation was
      found to be an independent predictor of lymph node metastasis in the study
      population. Comprehensive surgical staging including retroperitoneal node
      dissection should be strongly considered in all endometrial cancer patients with
      predominantly mucinous histology.

PMID- 22410329
TI  - Relapse rates after two versus three consolidation courses of methotrexate in the
      treatment of low-risk gestational trophoblastic neoplasia.
AB  - OBJECTIVE: Methotrexate (MTX) alternating with folinic acid is a commonly used
      treatment regimen for low-risk gestational trophoblastic neoplasia (GTN). In The
      Netherlands, two courses of MTX are administered after normalization of serum
      human chorionic gonadotrophin (hCG) levels (consolidation courses), whereas in
      the United Kingdom, three consolidation courses are given. In a retrospective
      setting we compared relapse rates of women completing MTX therapy for low-risk
      GTN in The Netherlands and the UK. METHODS: From 1980 to 2008, 351 patients were
      collected from the Dutch Central Registry for Hydatidiform Moles and records from
      the Dutch Working Party on Trophoblastic Disease. From the Charing Cross Hospital
      Trophoblast Disease Centre (London), 600 low-risk GTN patients were identified
      from 1992 to 2008. RESULTS: In 4.0% of patients relapse occurred after MTX
      treatment with three consolidation courses, whereas 8.3% of patients relapsed
      after MTX treatment with two consolidation courses (p=0.006). Although patients
      from The Netherlands had a higher level of hCG (p<0.001) and more patients had
      metastases before the start of treatment (p=0.012), the number of courses of MTX
      to achieve a normal hCG did not differ significantly between patients from The
      Netherlands and the UK (p=0.375). CONCLUSIONS: Relapse rates were higher in
      patients treated with two consolidation courses of MTX. Although other factors
      might have influenced the observed difference in relapse rates, three courses of
      consolidation chemotherapy may be preferable to two in the treatment of low-risk
      GTN in order to decrease the risk of disease relapse. A prospective randomized
      study would be required to confirm these findings.

PMID- 22410330
TI  - Allergic rhinitis in northern vietnam: increased risk of urban living according
      to a large population survey.
AB  - BACKGROUND: Little is known about prevalence and risk factors of allergic
      rhinitis and chronic nasal symptoms among adults in Vietnam. We aimed to estimate
      the prevalence, risk factor patterns and co-morbidities of allergic rhinitis and
      chronic nasal symptoms in one urban and one rural area in northern Vietnam.
      METHODS: A cross-sectional questionnaire survey was conducted from August 2007 to
      January 2008 in urban Hoankiem and rural Bavi in Hanoi among adults aged 21-70
      years. Of 7008 randomly selected subjects, 91.7% participated in Bavi and 70.3%
      in Hoankiem. RESULTS: Allergic rhinitis ever or chronic nasal symptoms were
      reported by 50.2%. The prevalence of allergic rhinitis ever was considerably
      higher in Hoankiem compared to Bavi, 29.6% vs 10.0% (p < 0.001). Allergic
      rhinitis ever and chronic nasal symptoms were both significantly associated with
      asthma and respiratory symptoms, respectively (p < 0.001). Exposure to gas, dust
      or fumes at work was significantly associated with allergic rhinitis ever, OR
      1.57 (95% CI 1.34 - 1.84), nasal blocking, OR 1.90 (95% CI 1.68 - 2.15) and runny
      nose, OR 1.32 (95% CI 1.17 - 1.49), while somewhat surprisingly no association
      with smoking was found. Female sex was a significant risk factor for both nasal
      blocking and runny nose. CONCLUSIONS: Allergic rhinitis ever was considerably
      more common in the urban area. Nasal blocking and runny nose was each reported by
      about one third of the studied sample with no major urban-rural difference.
      Further, exposure to air pollution at work was significantly associated with
      allergic rhinitis ever, nasal blocking and runny nose.

PMID- 22410332
TI  - A convex model for nonnegative matrix factorization and dimensionality reduction
      on physical space.
AB  - A collaborative convex framework for factoring a data matrix  X into a
      nonnegative product  AS , with a sparse coefficient matrix   S, is proposed. We
      restrict the columns of the dictionary matrix  A  to coincide with certain
      columns of the data matrix   X, thereby guaranteeing a physically meaningful
      dictionary and dimensionality reduction. We use   l(1, infinity) regularization
      to select the dictionary from the data and show that this leads to an exact
      convex relaxation of  l(0) in the case of distinct noise-free data. We also show
      how to relax the restriction-to- X constraint by initializing an alternating
      minimization approach with the solution of the convex model, obtaining a
      dictionary close to but not necessarily in  X. We focus on applications of the
      proposed framework to hyperspectral endmember and abundance identification and
      also show an application to blind source separation of nuclear magnetic resonance
      data.

PMID- 22410333
TI  - Comment on "Cheating prevention in visual cryptography".
AB  - Visual cryptography (VC), proposed by Naor and Shamir, has numerous applications,
      including visual authentication and identification, steganography, and image
      encryption. In 2006, Horng  showed that cheating is possible in VC, where some
      participants can deceive the remaining participants by forged transparencies.
      Since then, designing cheating-prevention visual secret-sharing (CPVSS) schemes
      has been studied by many researchers. In this paper, we cryptanalyze the Hu-Tzeng
      CPVSS scheme and show that it is not cheating immune. We also outline an
      improvement that helps to overcome the problem.

PMID- 22410334
TI  - Adaptive hypergraph learning and its application in image classification.
AB  - Recent years have witnessed a surge of interest in graph-based transductive image
      classification. Existing simple graph-based transductive learning methods only
      model the pairwise relationship of images, however, and they are sensitive to the
      radius parameter used in similarity calculation. Hypergraph learning has been
      investigated to solve both difficulties. It models the high-order relationship of
      samples by using a hyperedge to link multiple samples. Nevertheless, the existing
      hypergraph learning methods face two problems, i.e., how to generate hyperedges
      and how to handle a large set of hyperedges. This paper proposes an adaptive
      hypergraph learning method for transductive image classification. In our method,
      we generate hyperedges by linking images and their nearest neighbors. By varying
      the size of the neighborhood, we are able to generate a set of hyperedges for
      each image and its visual neighbors. Our method simultaneously learns the labels
      of unlabeled images and the weights of hyperedges. In this way, we can
      automatically modulate the effects of different hyperedges. Thorough empirical
      studies show the effectiveness of our approach when compared with representative
      baselines.

PMID- 22410335
TI  - Progressive significance map and its application to error-resilient image
      transmission.
AB  - Set partition coding (SPC) has shown tremendous success in image compression.
      Despite its popularity, the lack of error resilience remains a significant
      challenge to the transmission of images in error-prone environments. In this
      paper, we propose a novel data representation called the progressive significance
      map (prog-sig-map) for error-resilient SPC. It structures the significance map
      (sig-map) into two parts: a high-level summation sig-map and a low-level
      complementary sig-map (comp-sig-map). Such a structured representation of the sig
      map allows us to improve its error-resilient property at the price of only a
      slight sacrifice in compression efficiency. For example, we have found that a
      fixed-length coding of the comp-sig-map in the prog-sig-map renders 64% of the
      coded bitstream insensitive to bit errors, compared with 40% with that of the
      conventional sig-map. Simulation results have shown that the prog-sig-map can
      achieve highly competitive rate-distortion performance for binary symmetric
      channels while maintaining low computational complexity. Moreover, we note that
      prog-sig-map is complementary to existing independent packetization and channel
      coding-based error-resilient approaches and readily lends itself to other source
      coding applications such as distributed video coding.

PMID- 22410336
TI  - No-reference image quality assessment using visual codebooks.
AB  - The goal of no-reference objective image quality assessment (NR-IQA) is to
      develop a computational model that can predict the human-perceived quality of
      distorted images accurately and automatically without any prior knowledge of
      reference images. Most existing NR-IQA approaches are distortion specific and are
      typically limited to one or two specific types of distortions. In most practical
      applications, however, information about the distortion type is not really
      available. In this paper, we propose a general-purpose NR-IQA approach based on
      visual codebooks. A visual codebook consisting of Gabor-filter-based local
      features extracted from local image patches is used to capture complex statistics
      of a natural image. The codebook encodes statistics by quantizing the feature
      space and accumulating histograms of patch appearances. This method does not
      assume any specific types of distortions; however, when evaluating images with a
      particular type of distortion, it does require examples with the same or similar
      distortion for training. Experimental results demonstrate that the predicted
      quality score using our method is consistent with human-perceived image quality.
      The proposed method is comparable to state-of-the-art general-purpose NR-IQA
      methods and outperforms the full-reference image quality metrics, peak signal-to
      noise ratio and structural similarity index on the Laboratory for Image and Video
      Engineering IQA database.

PMID- 22410337
TI  - Multirate-based fast parallel algorithms for 2-D DHT-based real-valued discrete
      Gabor transform.
AB  - Novel algorithms for the multirate and fast parallel implementation of the 2-D
      discrete Hartley transform (DHT)-based real-valued discrete Gabor transform
      (RDGT) and its inverse transform are presented in this paper. A 2-D multirate
      based analysis convolver bank is designed for the 2-D RDGT, and a 2-D multirate
      based synthesis convolver bank is designed for the 2-D inverse RDGT. The parallel
      channels in each of the two convolver banks have a unified structure and can
      apply the 2-D fast DHT algorithm to speed up their computations. The
      computational complexity of each parallel channel is low and is independent of
      the Gabor oversampling rate. All the 2-D RDGT coefficients of an image are
      computed in parallel during the analysis process and can be reconstructed in
      parallel during the synthesis process. The computational complexity and time of
      the proposed parallel algorithms are analyzed and compared with those of the
      existing fastest algorithms for 2-D discrete Gabor transforms. The results
      indicate that the proposed algorithms are the fastest, which make them attractive
      for real-time image processing.

PMID- 22410339
TI  - cTNM vs. pTNM: the effect of not applying ultrasonography in the identification
      of cervical nodal disease.
AB  - Accurate clinical staging of oral squamous cell cancer can be quite difficult to
      achieve especially if nodal involvement is identified. Radiologically-assisted
      clinical staging is more accurate and informs the clinician of loco-regional and
      distant metastasis.In this study, we compared clinical TNM (cTNM) staging (not
      including ultrasonography) to pathological TNM (pTNM) staging in 245 patients
      presenting with carcinoma of the oral cavity and the oro-pharyngeal region.
      Tumour size differences and nodal involvement were highlighted. US reports of the
      neck were then added to the clinical staging and results compared.Tumour size was
      clinically underestimated in 4 T1, 2 T2 and 2 T3 oral diseases. Also 20 patients
      that were reported as nodal disease free had histological proven N1 or N2 nodal
      involvement; while 3 patients with cTNM showing N1 disease had histologically
      proven N2 disease.Overall the agreement between the 2 systems per 1 site was
      86.6% (Kappa agreement = 0.80), per 2 sites 90.0% (Kappa agreement = 0.68) and
      per 3 sites 90.5% (Kappa agreement 0.62).An accurate clinical staging is of an
      utmost importance. It is the corner stone in which the surgical team build the
      surgical treatment plan and decide whether an adjuvant therapy is required to
      deal with any possible problem that might arise. The failure to achieve an
      accurate staging may lead to incomplete surgical planning and hence unforeseen
      problems that may adversely affect the patient's survival.

PMID- 22410338
TI  - High-frequency neuronal network modulations encoded in scalp EEG precede the
      onset of focal seizures.
AB  - Modulations of neuronal network interactions by seizure precursors are only
      partially understood and difficult to measure, in part due to inherent intra- and
      inter-patient seizure heterogeneities and EEG variability. This study
      investigated preictal neuromodulations associated with seizures originating in
      the temporal and/or frontal lobes, using information theoretic parameters
      estimated from awake scalp EEGs in two frequency ranges, <=100 Hz and >100 Hz,
      respectively. Seizure-related activity at high frequencies has not been
      extensively estimated in awake scalp EEGs. Based on the statistical similarity of
      preictal and ictal information parameters, preictal network interactions appeared
      to be specifically modulated at frequencies >100 Hz, but not at lower
      frequencies. The dynamics of these parameters varied distinctly according to the
      origin of seizure onset (temporal versus frontal). Although preliminary, and
      based on a small patient sample for which the potential heterogeneity of multiple
      anticonvulsive medications was difficult to control, these results suggest that
      preictal modulations may be estimated from high-frequency scalp EEGs using
      directional information measures with high specificity to ictal events, and may
      thus be promising for improving seizure prediction.

PMID- 22410340
TI  - Genetic variants in the MRPS30 region and postmenopausal breast cancer risk.

PMID- 22410341
TI  - GABA(A) and GABA(B) receptors have opposite effects on synaptic glutamate release
      on the nucleus tractus solitarii neurons.
AB  - Cranial visceral afferent nerve transfers information about visceral organs to
      nucleus tractus solitarii (NTS) by releasing the excitatory neurotransmitter
      glutamate. Various endogenous modulators affect autonomic reflex responses by
      changing glutamatergic responses in the NTS. Although the expression of GABA(A)
      and GABA(B) receptors in glutamatergic terminals is known, their functional
      contribution on glutamate release is poorly characterized. Here, we used
      mechanically isolated NTS neurons to examine the mechanisms by which presynaptic
      GABA(A) and GABA(B) receptors modulate glutamatergic excitatory postsynaptic
      currents (EPSCs). EPSC were isolated by clamping voltage at equilibrium potential
      for chloride (-49 mV) without any GABA receptors antagonists. In all neurons,
      GABA(A) agonist, muscimol (1 and 10 MUM), increased EPSC frequency (284.1+/-57%
      and 278.4+/-87% of control, respectively), but the GABA(B) agonist, baclofen (10
      MUM), decreased EPSC frequency (43+/-8% of control). The GABA(A) antagonist,
      gabazine (18 MUM), decreased EPSC frequency in 50% of tested neurons, whereas
      GABA(B) antagonist, CGP (5 MUM), increased the EPSC frequency in 36% of tested
      neurons. External application of GABA (1 and 30 MUM) facilitating the EPSC
      frequency. The facilitation of the GABA(A) receptor-mediated release of glutamate
      was blocked by Na+-K+-Cl- cotransporter type 1 antagonist or Na+ and Ca2+ channel
      inhibitors indicating GABA(A) presynaptic depolarization. Thus, tonically
      released GABA activates GABA(A) and GABA(B) receptors to modulate the release of
      glutamate. These findings provide cellular mechanisms of heterosynaptic GABA
      glutamate integration of peripheral visceral afferent signals in the NTS.

PMID- 22410342
TI  - Antidepressants reduce extinction-induced withdrawal and biting behaviors: a
      model for depressive-like behavior.
AB  - The withholding of expected rewards results in extinction of behavior and,
      hypothetically, to depression-like symptoms. In a test of this hypothesis, we
      examined the effects of extinction of food-reinforced lever-pressing on
      collateral behaviors that might be indices of depression. Operant extinction is
      known to be aversive to the organism and results in avoidance behavior. We
      hypothesized that avoidance of, or withdrawal from, the former source of reward
      may serve as a marker for "despair." Adult male Wistar rats (n=6-7 animals per
      group) were exposed to a Skinner box attached to a second compartment of the same
      size, providing opportunity for the animals to leave the operant chamber and to
      enter the "withdrawal" compartment. The animals spent a portion of the time
      during the extinction trials in this second chamber. To assess the predictive
      validity of this behavior as a potential marker of "despair," we tested the
      effects of chronic administration of two common antidepressant drugs on this
      measure. The tricyclic antidepressant imipramine (20 mg/kg) as well as the
      selective serotonin reuptake inhibitor citalopram (20 mg/kg) reduced the number
      of entries and time spent in the withdrawal compartment. We propose that entries
      into and time spent in the withdrawal compartment may operationalize "avoidance,"
      a core symptom of major depression. Rearing as well as biting behaviors during
      the extinction trials were also attenuated by the antidepressant treatment. These
      results lend support to the hypothesis that extinction of positively reinforced
      operants evokes behaviors that reflect elements of "despair/depression" because
      these behaviors are modulated by antidepressant treatment. The avoidance of the
      operant chamber as a consequence of extinction, together with rearing and biting
      behaviors, may serve as useful measures for the testing of antidepressant
      treatments.

PMID- 22410343
TI  - Oral contraceptive use in women is associated with defeminization of otoacoustic
      emission patterns.
AB  - The production of otoacoustic emissions (OAEs) by the cochlea is a sexually
      dimorphic trait. Although often hypothesized to be influenced by testosterone in
      utero, little attention has been devoted to the possibility that levels of
      circulating sex steroids in adulthood might modulate the sex difference in OAE
      production. The purpose of the current study was to investigate whether oral
      contraceptive (OC) use affects OAE production in women, revisiting a question
      originally posed by McFadden [(2000) Hearing Research 142:23-33]. Forty-five
      males and 50 females were tested. The women were retrospectively classified based
      on whether or not they were using OCs at present. Two types of OAEs were
      quantified: those produced spontaneously (spontaneous otoacoustic emissions or
      SOAEs) and those produced in response to click stimuli (click-evoked otoacoustic
      emissions or CEOAEs). Women currently using OCs showed a defeminized pattern of
      OAE production: they produced fewer SOAEs, SOAEs with significantly less power,
      and smaller CEOAE response amplitudes compared with naturally cycling women who
      were tested irrespective of phase of the menstrual cycle. It is proposed that the
      observed group difference may be mediated by the interaction of circulating
      estradiol with estrogen receptor alpha (ERalpha) or estrogen receptor beta
      (ERbeta) receptors in the cochlea.

PMID- 22410344
TI  - The influence of maltose modified poly(propylene imine) dendrimers on hen egg
      white lysozyme structure and thermal stability.
AB  - In this study the influence of dendrimers' surface modification upon the strength
      of interaction with proteins was examined. Unmodified, cationic poly(propylene
      imine) dendrimer of the fourth generation (PPI G4), two PPI G4 dendrimers,
      partially and fully coated with maltose residues, and anionic polyamidoamine
      dendrimer of the third and a half generation (PAMAM G3.5 dendrimer), were used in
      the study. Hen egg white lysozyme, which possesses a cationic net charge under
      physiological conditions, was chosen as a model protein. The influence of
      dendrimers on the thermal stability of lysozyme was studied using differential
      scanning calorimetry (DSC) and circular dichroism (CD) methods. Additionally, the
      effect of dendrimers on the availability of lysozyme tryptophan residues to
      fluorescence quenchers was examined. It was shown that modification of dendrimer
      surface with maltose reduced its influence on lysozyme properties. However, even
      full surface modification, resulting in a neutral surface charge, did not deprive
      dendrimer of the ability to interact with the protein. It was probably caused by
      the introduction of a large number of hydroxyl groups from maltose residues on
      the surface of the dendrimer. In the study a comparable strength of influence
      exerted on lysozyme by cationic PPI dendrimer and anionic PAMAM G3.5 dendrimer
      was observed. The possible explanation of this fact is the presence of both
      positively and negatively charged areas on the surface of lysozyme. Such areas
      allow dendrimers possessing opposite surface charges to interact with lysozyme.

PMID- 22410345
TI  - A New Biased Discriminant Analysis Using Composite Vectors for Eye Detection.
AB  - We propose a new biased discriminant analysis (BDA) using composite vectors for
      eye detection. A composite vector consists of several pixels inside a window on
      an image. The covariance of composite vectors is obtained from their inner
      product and can be considered as a generalization of the covariance of pixels.
      The proposed composite BDA (C-BDA) method is a BDA using the covariance of
      composite vectors. We construct a hybrid cascade detector for eye detection,
      using Haar-like features in the earlier stages and composite features obtained
      from C-BDA in the later stages. The proposed detector runs in real time; its
      execution time is 5.5 ms on a typical PC. The experimental results for the CMU
      PIE database and our own real-world data set show that the proposed detector
      provides robust performance to several kinds of variations such as facial pose,
      illumination, eyeglasses, and partial occlusion. On the whole, the detection rate
      per pair of eyes is 98.0% for the 3604 face images of the CMU PIE database and
      95.1% for the 2331 face images of the real-world data set. In particular, it
      provides a 99.7% detection rate for the 2120 CMU PIE images without glasses. Face
      recognition performance is also investigated using the eye coordinates from the
      proposed detector. The recognition results for the real-world data set show that
      the proposed detector gives similar performance to the method using manually
      located eye coordinates, showing that the accuracy of the proposed eye detector
      is comparable with that of the ground-truth data. 

PMID- 22410346
TI  - A hybrid decision support model to discover informative knowledge in diagnosing
      acute appendicitis.
AB  - BACKGROUND: The aim of this study is to develop a simple and reliable hybrid
      decision support model by combining statistical analysis and decision tree
      algorithms to ensure high accuracy of early diagnosis in patients with suspected
      acute appendicitis and to identify useful decision rules. METHODS: We enrolled
      326 patients who attended an emergency medical center complaining mainly of acute
      abdominal pain. Statistical analysis approaches were used as a feature selection
      process in the design of decision support models, including the Chi-square test,
      Fisher's exact test, the Mann-Whitney U-test (p < 0.01), and Wald forward
      logistic regression (entry and removal criteria of 0.01 and 0.05, or 0.05 and
      0.10, respectively). The final decision support models were constructed using the
      C5.0 decision tree algorithm of Clementine 12.0 after pre-processing. RESULTS: Of
      55 variables, two subsets were found to be indispensable for early diagnostic
      knowledge discovery in acute appendicitis. The two subsets were as follows: (1)
      lymphocytes, urine glucose, total bilirubin, total amylase, chloride, red blood
      cell, neutrophils, eosinophils, white blood cell, complaints, basophils, glucose,
      monocytes, activated partial thromboplastin time, urine ketone, and direct
      bilirubin in the univariate analysis-based model; and (2) neutrophils,
      complaints, total bilirubin, urine glucose, and lipase in the multivariate
      analysis-based model. The experimental results showed that the model with
      univariate analysis (80.2%, 82.4%, 78.3%, 76.8%, 83.5%, and 80.3%) outperformed
      models using multivariate analysis (71.6%, 69.3%, 73.7%, 69.7%, 73.3%, and 71.5%
      with entry and removal criteria of 0.01 and 0.05; 73.5%, 66.0%, 80.0%, 74.3%,
      72.9%, and 73.0% with entry and removal criteria of 0.05 and 0.10) in terms of
      accuracy, sensitivity, specificity, positive predictive value, negative
      predictive value, and area under ROC curve, during a 10-fold cross validation. A
      statistically significant difference was detected in the pairwise comparison of
      ROC curves (p < 0.01, 95% CI, 3.13-14.5; p < 0.05, 95% CI, 1.54-13.1). The larger
      induced decision model was more effective for identifying acute appendicitis in
      patients with acute abdominal pain, whereas the smaller induced decision tree was
      less accurate with the test data. CONCLUSIONS: The decision model developed in
      this study can be applied as an aid in the initial decision making of clinicians
      to increase vigilance in cases of suspected acute appendicitis.

PMID- 22410347
TI  - Arthritis as a presenting symptom of subclinical Crohn's disease.

PMID- 22410348
TI  - Detection of CMV in pouch mucosa in a patient with acute pouchitis: the real
      enemy or an innocent bystander?

PMID- 22410349
TI  - Elevated levels of serum-soluble triggering receptor expressed on myeloid cells-1
      in patients with IBD do not correlate with intestinal TREM-1 mRNA expression and
      endoscopic disease activity.
AB  - BACKGROUND & AIMS: Triggering receptor expressed on myeloid cells-1 (TREM-1) is a
      potent amplifier of pro-inflammatory responses. We have previously demonstrated a
      substantial increase in TREM-1-expressing macrophages in the inflamed intestinal
      mucosa of patients with inflammatory bowel diseases (IBD). TREM-1 is also
      produced as a soluble receptor (sTREM-1). Here, we aimed to determine whether
      serum sTREM-1 could be used as a surrogate marker of disease activity in patients
      with IBD. METHODS: Intestinal biopsies and concurrently collected sera from
      patients with Crohn's disease (CD) and Ulcerative colitis (UC) enrolled in the
      Swiss IBD cohort study were analyzed for intestinal TREM-1 mRNA and serum sTREM-1
      expression. TREM-1 mRNA and sTREM-1 were correlated with the endoscopically
      determined disease activity. Serum sTREM-1 and TREM-1 mRNA expression levels were
      further determined in sera and colonic tissues collected at various time-points
      post disease induction in an experimental mouse model of colitis and correlated
      with disease activity. RESULTS: Expression of TREM-1 mRNA was upregulated in
      intestinal biopsies from patients with active disease but not in patients with
      quiescent disease. Serum sTREM-1 was elevated in IBD patients compared to normal
      controls. No substantial differences in sTREM-1 expression levels were found in
      patients with active versus quiescent disease. In colitic mice, colonic TREM-1
      mRNA and serum sTREM-1 were also upregulated. While colonic TREM-1 mRNA
      expression levels correlated with disease activity, augmented serum sTREM-1 in
      fact associated with a milder course of disease. CONCLUSIONS: Analysis of sTREM-1
      as a surrogate marker of disease activity in patients with IBD warrants caution.

PMID- 22410350
TI  - Changes in anterior segment morphology after laser peripheral iridotomy: an
      anterior segment optical coherence tomography study.
AB  - PURPOSE: Novel anterior segment optical coherence tomography (ASOCT) parameters
      associated with angle closure include anterior chamber area (ACA), anterior
      chamber volume (ACV), anterior chamber width (ACW), lens vault (LV), iris
      thickness (IT), iris area (I-area), and iris curvature (I-curv). We aimed to
      investigate changes in these parameters after laser peripheral iridotomy (LPI) in
      a cohort of primary angle-closure suspects (PACS). DESIGN: Prospective
      observational study. PARTICIPANTS AND CONTROLS: A total of 176 PACS aged >= 50
      years who underwent LPI in 1 eye. METHODS: We analyzed ASOCT images (Visante,
      Carl Zeiss Meditec, Dublin, CA) from all subjects using customized software
      before and 1 week after LPI. Multivariate linear regression analysis was
      performed for predictors of percentage change in mean angle opening distance
      (AOD750). MAIN OUTCOME MEASURES: Change in ASOCT parameters after LPI. RESULTS:
      The mean age of participants was 63 +/- 7.3 years. The majority of subjects were
      Chinese (95.5%) and women (76.7%). Mean angle width (modified Shaffer grade)
      changed from 0.68 +/- 0.54 at baseline to 1.76+/-0.69 after LPI (P<0.001) with a
      corresponding increase in mean AOD500 (0.12 vs. 0.19 mm, P<0.001), trabecular
      iris surface area (TISA500, 0.06 vs. 0.08 mm(2), P<0.001), and angle recess area
      (ARA, 0.13 vs. 0.17 mm(2), P<0.001). Mean ACA (15.0 vs. 16.0 mm(2), P<0.001) and
      ACV (91.6 vs. 103.0 mm(3), P<0.001) increased significantly after LPI, but there
      was no change in ACW, anterior chamber depth (ACD), or LV. Mean I-curv was
      reduced (0.375 vs. 0.18 mm, P<0.001) after LPI, but there was no significant
      change in IT or I-area. After multivariate analysis, mean LV (beta = 0.286, P =
      0.001), mean IT at 2000 MUm (IT2000, beta = 0.172, P = 0.034), and intraocular
      pressure (beta = 0.159, P = 0.042) at baseline were found to be associated with
      DeltaAOD750. CONCLUSIONS: This study confirms that LPI results in a significant
      increase in the angle width in PACS. The ACA and ACV increased after LPI, but
      there was no change in ACD, ACW, LV, IT, or I-area. The increase in ACA/ACV was
      mainly due to decreased I-curv after LPI.

PMID- 22410351
TI  - Characterization of Coptis japonica CjABCB2, an ATP-binding cassette protein
      involved in alkaloid transport.
AB  - Higher plants produce a large number of secondary metabolites. Among these are
      the alkaloids, a group of small nitrogen-containing molecules. Alkaloids often
      have strong biological activity that protects alkaloid-producing plants from
      herbivores, and often accumulate to high concentrations in a specific organelle
      of a particular organ in the producing plant. However, knowledge of the membrane
      transport mechanism of alkaloids is still limited. Coptis japonica, a perennial
      Ranunculaceous plant, produces the benzylisoquinoline alkaloid berberine. This
      alkaloid, though biosynthesized in root tissues, accumulates in the rhizome,
      suggesting translocation of the molecule via xylem. In this study, a gene
      encoding a ATP-binding cassette (ABC) protein of B-type, Cjabcb2, was isolated
      from C. japonica. Northern analysis showed that Cjabcb2 was preferentially
      expressed in the rhizome, which is the sink organ of berberine. Functional
      analysis of CjABCB2 using yeast suggested that CjABCB2 transports berberine in an
      inward direction. Membrane separation and in situ hybridization data indicated
      that CjABCB2 might be involved in translocation of berberine from the root to the
      rhizome by transporting berberine at the plasma membrane of cells around the
      xylem of the rhizome.

PMID- 22410352
TI  - alpha-Santalol derivatives from Santalum album and their cytotoxic activities.
AB  - A bioassay-guided fractionation of the heartwood of Santalum album led to the
      isolation of seven alpha-santalol derivatives including (9S,10E)-9-hydroxy-alpha
      santalal, (10R,11S)-10,11-dihydroxy-alpha-santalol, (9E)-11,13-dihydroxy-alpha
      santalol, and (10E)-12-hydroxy-alpha-santalic acid. Their structures were
      determined on the basis of results of spectroscopic analysis, including two
      dimensional (2D) NMR spectroscopic data. The isolated compounds and derivatives
      were evaluated for cytotoxicity against HL-60 human promyelocytic leukemia cells
      and TIG-3 normal human diploid fibroblasts. Of these (9S,10E)-9-hydroxy-alpha
      santalal, exhibited tumor-selective cytotoxicity. The apoptosis induction
      properties of sesquiterpenes with cytotoxic potency in HL-60 cells are also
      described.

PMID- 22410353
TI  - Treatment of multidrug-resistant tuberculosis in a high-prevalence region through
      a binational consortium.
AB  - We describe the outcome of treatment of multidrug-resistant tuberculosis (MDR-TB)
      in Baja California, Mexico, by a United States-Mexico consortium. From June 2006
      to December 2010, 42 patients started treatment. Strains were resistant to 4.15
      +/- 1.3 drugs; all patients achieved  culture conversion on treatment after an
      average of 3.4 +/- 1.6 months. A total of 19 patients (47.5%) were discharged as
      cured, 3 died (7.5%) and 1 defaulted (2.5%). MDR-TB cases can be cured under a
      well-organized out-patient program; in this consortium, the US partner introduced
      program  elements that were gradually integrated into the Mexican state TB
      program.

PMID- 22410354
TI  - Should immunosuppressives be stopped in granulomatosis with polyangiitis
      (Wegener's granulomatosis) patients undergoing dialysis?
AB  - Immunosuppressives are frequently stopped in patients with granulomatosis with
      polyangiitis (GPA) (Wegener's granulomatosis) who develop end-stage renal
      disease. This is done because of the high frequency of infections reported among
      dialysis patients under immunosuppressives and the former impression that GPA
      patients no longer experience relapses after the development of end-stage renal
      disease. We present here a 22-year-old male patient with GPA who had
      gastrointestinal, genitourinary and respiratory system involvement. The patient
      died because of a gastrointestinal disease activation that occurred after
      immunosuppressives were stopped at the initiation of dialysis. The decision to
      stop immunosuppressives while starting dialysis should be made on an individual
      basis in patients with GPA, and the risks and benefits should be carefully
      evaluated.

PMID- 22410355
TI  - A novel approach for finding ring species: look for barriers rather than rings.
AB  - Ring species, in which two different forms coexist in one region while being
      connected by a long chain of interbreeding populations encircling a geographic
      barrier, provide clear demonstrations of the evolution of one species into two.
      Known ring species are rare, but now Monahan et al. propose an intriguing new
      approach to discovering them: focus first on geography to find potential
      barriers.See research article http://www.biomedcentral.com/1741-7007/10/20.

PMID- 22410356
TI  - [Acute amoebic appendicitis].

PMID- 22410357
TI  - Letter from the guest editors: thyroid and parathyroid imaging.

PMID- 22410358
TI  - Anatomy and embryology of the thyroid and parathyroid glands.
AB  - The thyroid and parathyroid glands are cervical endocrine glands responsible for
      metabolism-related functions. Radiologists are frequently asked to evaluate
      pathology related to the thyroid and parathyroid glands before planned surgical
      intervention. Knowledge of embryology and anatomy is fundamental in this region
      because rather complex underlying embryology produces substantial anatomic
      variation both in the thyroid bed and elsewhere in the neck and mediastinum.

PMID- 22410359
TI  - Modern approach to surgical intervention of the thyroid and parathyroid glands.
AB  - Operative intervention on the parathyroid and thyroid glands has become more
      minimally invasive and selective over the past decade. This requires high-quality
      preoperative imaging evaluation for better knowledge of the relevant anatomical
      considerations and potential localization. Minimally invasive parathyroidectomy
      has become the operation of choice for most patients presenting with sporadic
      primary hyperparathyroidism (when the suspected parathyroid tumor is localized
      preoperatively). Preoperative imaging helps guide the surgeon as to which
      patients with thyroid pathology require intervention and the extent of resection.
      The imaging modalities reviewed include ultrasonography, technetium-99m sestamibi
      imaging, and four-dimensional computed tomography. Imaging modalities are
      discussed within the categories of benign and neoplastic parathyroid and thyroid
      pathology.

PMID- 22410360
TI  - Imaging of the parathyroid glands.
AB  - Parathyroid imaging is performed in the setting of primary hyperparathyroidism
      with intent to localize adenomatous parathyroid tissue before minimally invasive
      surgery. Available imaging options currently consist of ultrasound, radionuclide
      scanning, magnetic resonance imaging, and both conventional and "4 D" computed
      tomography. Various combinations of these modalities are used based primarily on
      institutional bias, and although highly successful in localizing the common
      single adenoma, they are less effective when there is multiglandular disease or
      glandular ectopia.

PMID- 22410361
TI  - Benign conditions of the thyroid gland.
AB  - Infectious and autoimmune diseases account for the majority of benign conditions
      of the thyroid gland. They are usually diagnosed and followed by clinical
      examination and laboratory analyses, but when imaged, ultrasonography and
      computed tomography are the modalities of choice. In particular, fine needle
      aspiration under ultrasound guidance may be invaluable for diagnostic and
      therapeutic purposes.

PMID- 22410362
TI  - Imaging of thyroid cancer.
AB  - Thyroid cancer is a heterogeneous group of malignancies, including differentiated
      thyroid carcinomas, medullary and anaplastic carcinomas, and non-Hodgkin
      lymphoma. The incidence, presentation, natural history, prognosis, and treatment
      vary greatly among this diverse group of malignancies. The primary role of
      imaging in thyroid cancer is to evaluate for extension of tumor beyond the
      thyroid capsule and to assess for nodal metastases. Ultrasound is the standard
      imaging option for uncomplicated thyroid cancer, but patients with symptoms
      suggesting extrathyroidal extension or palpable lateral lymphadenopathy should be
      considered for cross-sectional imaging with computed tomography or magnetic
      resonance imaging.

PMID- 22410363
TI  - What to do with incidental thyroid nodules on imaging? An approach for the
      radiologist.
AB  - The incidental thyroid nodule is a common finding on cross-sectional imaging of
      the neck and chest. Although the majority of nonpalpable incidental nodules are
      benign, the radiologist must assess the risk of malignancy, intelligently report
      the finding, and potentially direct the subsequent workup. To do so, the
      radiologist requires an understanding of issues around thyroid cancer, costs of
      thyroid nodule workup, and suspicious findings for malignancy. This article
      describes the problem of the incidental thyroid nodule, reviews the imaging
      findings of malignancy, and discusses an approach to reporting the incidental
      thyroid nodule.

PMID- 22410364
TI  - Thyroid nodule fine-needle aspiration.
AB  - Thyroid nodules are a common clinical problem and are noted much more commonly on
      imaging examinations than are apparent by palpation. Fine-needle aspiration
      biopsy (FNA), which yields a cytology specimen for analysis, is the standard test
      to determine whether surgical removal of a detected nodule is recommended. This
      article will review the current guidelines for recommending FNA of thyroid
      nodules, the technique and risk of the procedure, and the implications for
      patient care based on FNA results. FNA has an essential role in the evaluation of
      patients with thyroid nodules to reduce the rate of unnecessary thyroid surgery
      for patients with benign nodules and triage patients with thyroid cancer to
      appropriate surgery. Before the routine use of FNA, approximately 14% of resected
      thyroid nodules were malignant, whereas with the current widespread use of
      thyroid nodule FNA, >50% of resected thyroid nodules are malignant. Historically,
      thyroid nodules were identified by physical examination of the neck, with a
      prevalence of approximately 5%-10% of adults in the United States, and these
      patients underwent palpation-guided FNA in the physician's office. In recent
      years, the increased use of sonography to examine the thyroid as well as cross
      sectional imaging of the neck by computed tomography and magnetic resonance
      imaging has resulted in the detection of many nonpalpable nodules. In older
      adults, thyroid nodules may be detected in >67% of people screened by sonography.
      Fortunately, the vast majority of nodules are benign, but when they are
      discovered, an assessment regarding the need to exclude malignancy using FNA must
      be performed.

PMID- 22410366
TI  - Computational mate choice: theory and empirical evidence.
AB  - The present review is based on the thesis that mate choice results from
      information-processing mechanisms governed by computational rules and that, to
      understand how females choose their mates, we should identify which are the
      sources of information and how they are used to make decisions. We describe mate
      choice as a three-step computational process and for each step we present
      theories and review empirical evidence. The first step is a perceptual process.
      It describes the acquisition of evidence, that is, how females use multiple cues
      and signals to assign an attractiveness value to prospective mates (the
      preference function hypothesis). The second step is a decisional process. It
      describes the construction of the decision variable (DV), which integrates
      evidence (private information by direct assessment), priors (public information),
      and value (perceived utility) of prospective mates into a quantity that is used
      by a decision rule (DR) to produce a choice. We make the assumption that females
      are optimal Bayesian decision makers and we derive a formal model of DV that can
      explain the effects of preference functions, mate copying, social context, and
      females' state and condition on the patterns of mate choice. The third step of
      mating decision is a deliberative process that depends on the DRs. We identify
      two main categories of DRs (absolute and comparative rules), and review the
      normative models of mate sampling tactics associated to them. We highlight the
      limits of the normative approach and present a class of computational models
      (sequential-sampling models) that are based on the assumption that DVs accumulate
      noisy evidence over time until a decision threshold is reached. These models
      force us to rethink the dichotomy between comparative and absolute decision
      rules, between discrimination and recognition, and even between rational and
      irrational choice. Since they have a robust biological basis, we think they may
      represent a useful theoretical tool for behavioural ecologist interested in
      integrating proximate and ultimate causes of mate choice.

PMID- 22410367
TI  - Phosphodiesterase 5 inhibitors in vascular systemic disorders.

PMID- 22410365
TI  - IL-7 in human health and disease.
AB  - IL-7 plays many essential roles in human health and disease. Congenital
      deficiencies in IL-7 signaling result in profound immunodeficiency, polymorphisms
      in IL7Ralpha modulate susceptibility to autoimmune disease, and acquired somatic
      activating mutations in IL7Ralpha contribute to neoplastic transformation in B
      cell and T cell leukemia. In response to lymphopenia, IL-7 accumulates to
      supranormal levels, which alters T cell homeostasis by augmenting T cell
      reactivity toward self and cognate antigens. This physiologic response is now
      routinely exploited to improve the efficacy of adoptive cell therapies for
      cancer. Clinical trials of recombinant IL-7 have demonstrated safety and potent
      immunorestorative effects, and current studies are investigating whether rhIL-7
      therapy can improve outcomes in chronic viral infection and in the context of
      cancer immunotherapies. Building upon the large fund of knowledge regarding the
      basic biology of IL-7, this review will discuss the many and varied roles of IL-7
      in human health and disease.

PMID- 22410368
TI  - Incomplete thymic involution in systemic sclerosis and rheumatoid arthritis.
AB  - OBJECTIVE: The thymus plays a crucial role in immune system homeostasis. Thymic
      abnormalities have been reported in many autoimmune diseases, but data for
      systemic sclerosis (SSc) and rheumatoid arthritis (RA) are sparse. The aim of
      this study was to evaluate the prevalence and correlates of radiological
      incomplete involution of the thymus in SSc and RA patients, and in a non
      autoimmune group of controls. METHODS: All patients were at least 40 years old:
      96 SSc patients (median age 59 years, 80% women) and 65 RA patients (median age
      57 years, 88% women) were compared with 32 control individuals (median age 63
      years, 62% women). Pulmonary CT-scans performed for lung assessment were
      available for all individuals. For the purpose of our study, complete involution
      of the thymus was defined as the absence of a residual thymus or a gland
      thickness, corresponding to the short axis on the axial slice, of less than 7 mm.
      We defined incomplete involution of the thymus as a residual thymic tissue more
      than 7 mm thick. RESULTS: The frequency of incomplete thymus involution was
      significantly higher in SSc and RA patients (respectively 15 and 14%) than in the
      control group (0%; P<0.05). Incomplete thymus involution was associated with
      pulmonary restrictive syndrome in SSc patients, and with biotherapy and an
      absence of antinuclear antibodies in RA patients. CONCLUSION: Our findings show
      that two autoimmune diseases, SSc and RA, are associated with incomplete thymus
      involution.

PMID- 22410370
TI  - Treating multiple sclerosis with vitamin D.

PMID- 22410369
TI  - Expressions of matrix metalloproteinase-9 (MMP-9), dentin sialophosphoprotein
      (DSPP), and osteopontin (OPN) at histologically negative surgical margins may
      predict recurrence of oral squamous cell carcinoma.
AB  - Up to 50% of oral squamous cell carcinomas (OSCCs) recur following surgical
      resections with conventional "histologically-negative" margins. Three members of
      the SIBLING family of proteins: dentin sialophophoprotein (DSPP); bone
      sialoprotein (BSP); and osteopontin OPN are upregulated in OSCCs. In this study,
      we aimed to correlate the expression of DSPP, OPN and BSP as well as three
      SIBLING-partners, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-3
      (MMP-3), and matrix metalloproteinase-9 (MMP-9), at histologically-negative
      margins of OSCCs with tumor recurrence. Immunohistochemical analyses of the
      SIBLINGs and MMP expressions at histologically-negative margins of OSCC was
      carried out in a retrospective study of 20 patients, and the results correlated
      with tumor recurrence. Each protein was dichotomized as "present" (>=10%
      staining) or "absent" (more than 10% staining). The Sensitivity, Specificity,
      Positive Predictive Value(PV+) and Negative Predictive Value (PV-) for recurrence
      was calculated for each protein, along with their overall diagnostic accuracy,
      calculated as: (number of true positives + number of true negatives)/ number of
      patients. OSCC recurred in 9 of 20 patients (45%), a ratio not significantly
      different from the estimated population recurrence rate of 50% (p = 0.664). Among
      the SIBLINGs, DSPP and OPN showed the greatest Accuracy with DSPP being more
      Sensitive (89%) and OPN more Specific (64%). MMP-9 showed the greatest overall
      Accuracy (80%), slightly less Sensitivity (67%) and more Specificity (100%), than
      either DSPP or OPN. MMP-9 showed a superior positive PV than either DSPP or OPN.
      The negative PVs of OPN and MMP-9 were almost identical, and inferior to DSPP. We
      conclude that DSPP, OPN, or MMP-9 expressions at histologically-negative surgical
      margins predict OSCC recurrence with MMP-9 being the preferred predictor. These
      proteins may identify patients who could benefit from more extensive resection,
      or from adjunct treatments such as radiotherapy.

PMID- 22410371
TI  - Chaperones: friend or foe, and to whom?

PMID- 22410372
TI  - Calculating risk in use of disposable contact lenses.

PMID- 22410373
TI  - Severe edema and elevated CA 125 in a 56-year-old woman.

PMID- 22410376
TI  - Bleomycin-induced-flagellate dermatitis.

PMID- 22410375
TI  - Cost-effectiveness of diacetylmorphine versus methadone for chronic opioid
      dependence refractory to treatment.
AB  - BACKGROUND: Although diacetylmorphine has been proven to be more effective than
      methadone maintenance treatment for opioid dependence, its direct costs are
      higher. We compared the cost-effectiveness of diacetylmorphine and methadone
      maintenance treatment for chronic opioid dependence refractory to treatment.
      METHODS: We constructed a semi-Markov cohort model using data from the North
      American Opiate Medication Initiative trial, supplemented with administrative
      data for the province of British Columbia and other published data, to capture
      the chronic, recurrent nature of opioid dependence. We calculated incremental
      cost-effectiveness ratios to compare diacetylmorphine and methadone over 1-, 5-,
      10-year and lifetime horizons. RESULTS: Diacetylmorphine was found to be a
      dominant strategy over methadone maintenance treatment in each of the time
      horizons. Over a lifetime horizon, our model showed that people receiving
      methadone gained 7.46 discounted quality-adjusted life-years (QALYs) on average
      (95% credibility interval [CI] 6.91-8.01) and generated a societal cost of $1.14
      million (95% CI $736,800-$1.78 million). Those who received diacetylmorphine
      gained 7.92 discounted QALYs on average (95% CI 7.32-8.53) and generated a
      societal cost of $1.10 million (95% CI $724,100-$1.71 million). Cost savings in
      the diacetylmorphine cohort were realized primarily because of reductions in the
      costs related to criminal activity. Probabilistic sensitivity analysis showed
      that the probability of diacetylmorphine being cost-effective at a willingness-to
      pay threshold of $0 per QALY gained was 76%; the probability was 95% at a
      threshold of $100,000 per QALY gained. Results were confirmed over a range of
      sensitivity analyses. INTERPRETATION: Using mathematical modelling to extrapolate
      results from the North American Opiate Medication Initiative, we found that
      diacetylmorphine may be more effective and less costly than methadone among
      people with chronic opioid dependence refractory to treatment.

PMID- 22410377
TI  - Who should hold the keys to your DNA?

PMID- 22410378
TI  - Time to end ageism in medical education.

PMID- 22410379
TI  - Who should be privy to your privates?

PMID- 22410380
TI  - A race-based detour to personalized medicine.

PMID- 22410381
TI  - Clinical significance and outcome of polymicrobial Staphylococcus aureus
      bacteremia.
AB  - OBJECTIVES: The clinical significance of polymicrobial Staphylococcus aureus
      bacteremia (SAB) remains unclear. We therefore compared the clinical features and
      outcomes of polymicrobial and monomicrobial SAB. METHODS: A prospective cohort
      study of patients with SAB was performed during a 20-months. Polymicrobial SAB
      was defined as the simultaneous isolation of S. aureus and other microorganisms
      from blood cultures. However, Corynebacterium spp., Bacillus spp., and coagulase
      negative staphylococci were considered contaminants unless they were related to
      device infection and grew in two or more blood cultures. RESULTS: During the
      study period, 44 (10%) patients had polymicrobial and 412 (90%) had monomicrobial
      SAB. A total of 54 microorganisms were isolated from the former, with
      Enterococcus spp. (22%) being the most common. Independent risk factors for
      polymicrobial SAB included neutropenia (odds ratio [OR] 3.5, p = 0.02), biliary
      tract catheters (OR 5.0, p = 0.001), and intra-abdominal infection (OR 10.3, p <
      0.001). Clinical outcomes were significantly worse among patients with
      polymicrobial than monomicrobial SAB, including bacteremia-related and 7-day
      mortality rates. Independent predictors of bacteremia-related mortality were
      solid tumors (HR 2.0, p = 0.03) and polymicrobial SAB (HR 2.8, p = 0.007).
      CONCLUSIONS: Polymicrobial SAB is associated with more severe illness than
      monomicrobial SAB, with neutropenia, biliary tract catheters and intra-abdominal
      infection being significant risk factors for polymicrobial SAB.

PMID- 22410382
TI  - Biomarkers define the clinical response to dexamethasone in community-acquired
      pneumonia.
AB  - OBJECTIVES: Adjuvant dexamethasone treatment in patients with community-acquired
      pneumonia (CAP) can reduce length of hospital stay. Whether there are subgroups
      of patients that especially might benefit from corticosteroids is unknown. We
      hypothesized that a discrepancy between systemic inflammation and cortisol level
      can define a subgroup that lacks a sufficient cortisol response during CAP, and
      therefore particularly might benefit from corticosteroids. METHODS: A secondary
      analysis was performed on data from hospitalized patients with CAP, randomized to
      a four-day course of dexamethasone (5 mg daily) or placebo. Subgroups were made
      based on plasma cytokine levels (interleukin-6 (IL-6), interleukin-8 (IL-8),
      monocyte chemotactic protein-1 (MCP-1)) and total plasma cortisol on
      presentation. Intensive care unit (ICU) admission and mortality were assessed.
      RESULTS: 275 Patients (131 dexamethasone, 144 placebo) were analyzed. In the
      subgroup of patients (n = 23) with a high cytokine response (IL-6 >= 92.5 pg/mL,
      IL-8 >= 14.8 pg/mL and MCP-1 >= 1154.5 pg/mL) and a discrepantly low cortisol
      (lowest 50%), dexamethasone treatment was associated with a significant decrease
      on a combined endpoint of mortality/ICU admission, as compared with placebo (0%
      vs. 43%, p < 0.01). In the subgroup of patients with a high cytokine response and
      high cortisol (n = 23), this favorable effect of dexamethasone was absent (30%
      vs. 39%, p: 0.67). CONCLUSIONS: In CAP patients presenting with a high pro
      inflammatory cytokine response but a discrepantly low cortisol, adjuvant
      dexamethasone treatment was associated with a significant decrease in
      mortality/ICU admission.

PMID- 22410383
TI  - Immune response to hepatitis B vaccination in HIV-positive adults with isolated
      antibodies to HBV core antigen.
AB  - OBJECTIVE: To investigate the merits of vaccination against hepatitis B virus
      (HBV) in HIV-positive individuals with isolated antibodies to hepatitis B core
      antigen (anti-HBc). METHODS: HIV-positive patients with isolated anti-HBc and CD4
      counts >200 cells/mm(3) received HBV vaccination. An antibody titre to hepatitis
      B surface antigen (anti-HBs titres) >=10 IU/L one month post-vaccination was
      termed an anamnestic response; a titre <10 IU/L was termed a primary response.
      Patients with primary responses received a 3-dose vaccine course. Anti-HBs titres
      in all responders were measured 12 and 24 months post-vaccination. RESULTS: 37
      patients were studied: 19 (51%) were co-infected with hepatitis C; median CD4
      count was 443 cells/mm(3). 8/37 patients (22%) elicited an anamnestic response.
      29/37 patients (78%) elicited a primary response. After a 3-dose vaccine course,
      15/25 primary responders (60%) achieved anti-HBs titres >=10 IU/L. HIV
      acquisition through injecting drug use was the only independent predictor of an
      anamnestic response (OR 22.9, CI 1.71-306.74, P=0.018). Median anti-HBs titres
      for anamnestic and primary responders were 51 IU/L (13-127) and 157 IU/L (25-650)
      respectively. Of all responders, 12/23 (52%) retained anti-HBs titres >=10 IU/L
      at 24 months. Anti-HBs duration was not significantly different between
      anamnestic and primary responders. CONCLUSIONS: 23/37 HIV-positive patients (62%)
      with isolated anti-HBc achieved anti-HBs titres >=10 IU/L after 1-3 vaccine
      doses. However, duration of this immune response was short-lived (<two years) in
      over half the responders. The implications regarding re-infection risk in this
      population are yet to be determined.

PMID- 22410384
TI  - The risk of infections in HIV-HCV coinfected patients during antiviral therapy
      with pegIFN+RBV.
AB  - OBJECTIVES: Antiviral treatment with pegIFN/RBV decreases ANC and CD4+ cell
      count. An association between neutropenia, a low CD4+ cell count and infections
      has not been demonstrated so far in HIV-HCV coinfected patients. METHODS: The
      incidence, type, and severity of infections were recorded in 85 HIV-HCV
      coinfected and 164 monoinfected patients receiving pegIFN/RBV for 48 weeks. ANC
      and CD4+ cell count were assessed every 4 weeks during therapy. RESULTS: The
      incidence of infections was significantly higher in HIV-HCV than HCV-Mono (38%
      vs. 15%; p = 0.001). Types of infections: pneumonia (n = 16/n = 24),
      bacteraemia/sepsis (n = 5/n = 2), skin infections (n = 15/n = 12), urinary tract
      infections (n = 4/n = 1), OIs (n = 10/n = 1). The incidence of neutropenia grade
      1, 2 3 or 4 was similar in HIV-HCV and HCV-Mono, respectively. The incidence of
      infections was not associated with neutropenia (HCV-Mono: p = 0.584; HIV-HCV: p =
      0.23) or with CD4+ cell counts <200/MUL (HIV-HCV: p = 0.29). OIs occurred more
      often in HIV-HCV patients with CD4+ cell count <200/MUL (p = 0.024). CONCLUSIONS:
      Up to 38% and 15% of HIV-HCV coinfected and HCV-monoinfected patients develop
      infections during pegIFN+RBV therapy but without any correlation to neutropenia.
      Antibacterial prophylaxis/treatment should be considered early in HIV-HCV
      coinfected patients developing CD4+ cell counts <200/MUL during antiviral therapy
      as these patients have an increased risk of OIs.

PMID- 22410385
TI  - Multimodality treatment and long-term follow-up of the primary pulmonary
      lymphoepithelioma-like carcinoma.
AB  - INTRODUCTION: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a very
      rare subtype of non-small-cell lung cancer. Most cases are reported in Southeast
      Asia and are associated with Epstein-Barr virus infections. Because of its rare
      incidence, the optimal treatment and the results of long-term follow-up are not
      well understood. This study is an attempt to discover the multimodality treatment
      results of the primary pulmonary LELC. METHODS: This retrospective study enrolled
      21 patients with primary pulmonary LELC treated at 2 hospitals with a
      multimodality approach, including surgery, chemotherapy, radiotherapy, and
      targeted therapy. RESULTS: The median follow-up time is 5.9 years and the median
      survival is 6.4 years. The median overall survival for patients with stage III
      and with stage IV disease is 3.4 years. In early-stage primary pulmonary LELC,
      surgery and adjuvant chemotherapy provided good treatment outcome. Advanced
      primary pulmonary LELC is relatively more chemosensitive and radiosensitive.
      CONCLUSION: Patients with primary pulmonary LELC showed better prognosis than
      those with other types of non-small-cell lung cancer and achieved longer survival
      under multimodality treatment. This disease character is similar to that of
      nasopharyngeal carcinoma. Accurate pathologic diagnosis is recommended before the
      treatment. For advanced diseases, platinum-based doublet chemotherapy can be
      considered the first-line treatment. Radiation dose should consider tumor
      location, and 5000 to 7000 cGy is frequently applied for pulmonary LELC.

PMID- 22410386
TI  - Direct comparison of 3 PCR methods in detecting EGFR mutations in patients with
      advanced non-small-cell lung cancer.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are predictive of
      response to EGFR tyrosine kinase inhibitors (TKIs) in NSCLC. Several methods have
      been used to detect EGFR mutations; however, it is not clear which is the most
      suitable for use in the clinic. In this study, we directly compare the clinical
      sensitivity and specificity of 3 PCR methods. PATIENTS AND METHODS: We compared
      the 3 PCR methods (mutant-enriched PCR, PNA-LNA PCR, and PCR clamp) in patients
      with advanced NSCLC. A patient who showed sensitive mutations by at least 1 PCR
      method was treated with gefitinib. A patient who showed no sensitive mutations
      was treated with chemotherapy with cytotoxic agents. RESULTS: Fifty patients with
      advanced NSCLC previously untreated with EGFR-TKIs were enrolled in this trial.
      Seventeen patients were harboring EGFR mutations, 5 of whom showed discrepancies
      between the results of different PCR methods. All 5 patients responded to
      gefitinib. All patients harboring EGFR mutations received gefitinib treatment and
      21 of 33 EGFR-mutation-negative patients received chemotherapy with cytotoxic
      agents. Median progression-free survival of the gefitinib group and the
      chemotherapy group were 8.2 and 5.9 months, respectively. CONCLUSION: We
      considered that all the discrepancies might be false negatives because the
      patients responded to gefitinib. To clarify the reason for the false negatives of
      each PCR method, and establish the clinical sensitivity and specificity of each
      PCR method, a large prospective clinical trial is warranted.

PMID- 22410387
TI  - Evolving kinetics of gene expression in stochastic environments.
AB  - Recent studies have shown that the in vivo dynamics of RNA numbers in bacteria is
      regulated, to a great extent, by the kinetics of rate limiting steps in
      transcription. Strong evidence suggests that the kinetics of these steps is
      sequence dependent. We investigate the selective advantages of rate limiting
      steps of differing kinetics. For that, we model the kinetics of expression of a
      gene responsible for promoting cell division at the expense of resources in the
      environment in individual cells of a population. We model mutations that affect
      the kinetics of the rate limiting steps and selective pressure in various
      environmental conditions. Depletion of resources leads to cell death. We find
      that small changes in the evolutionary constraints can favor widely different
      noise levels in RNA and protein numbers. Increasing the cost in nutrients for
      division favors noisier expression. The results provide a better understanding of
      why different genes differ in the kinetics of production of RNA and proteins.

PMID- 22410388
TI  - Dietary patterns and risk of cardiovascular deaths among middle-aged Japanese:
      JACC Study.
AB  - BACKGROUND AND AIMS: Little evidence showed the association between dietary
      patterns and cardiovascular disease among Japanese. The objective of this study
      was to examine whether dietary patterns are associated with cardiovascular
      disease among middle-aged Japanese. METHODS AND RESULTS: At baseline (1988-1990),
      26,598 men and 37,439 women aged 40-79 years enrolled in the Japan Collaborative
      Cohort (JACC) Study. During the follow-up through 2003, 578 men and 499 women
      died from stroke, and 272 men and 207 women died from coronary heart disease. We
      identified three major dietary patterns, 'vegetable', 'animal food' and 'dairy
      product', by factor analysis for both sexes. The multivariable hazard ratio (HR)
      and 95% confidence intervals of mortality from total cardiovascular disease in
      the highest versus lowest quintiles of the vegetable pattern were 0.93 (0.78
      1.13), p for trend=0.73 for men and 0.82 (0.67-1.00), p for trend=0.04 for women.
      The respective HRs of mortality from stroke in the highest versus lowest
      quintiles of the dairy product pattern were 0.65 (0.49-0.86), p for trend=0.01
      for men and 0.70 (0.51-0.97), p for trend=0.02 for women, and those of total
      cardiovascular disease were 0.89 (0.74-1.08), p for trend=0.23 for men and 0.76
      (0.61-0.94), p for trend=0.01 for women. The animal food pattern was not
      associated with mortality from stroke, coronary heart disease or total
      cardiovascular disease for either sex. CONCLUSION: We found that 'vegetable' and
      'dairy product' patterns were associated with lower morality from cardiovascular
      disease, while the 'animal food' pattern was not associated with mortality from
      cardiovascular disease among Japanese.

PMID- 22410389
TI  - Protocol of a randomized cluster trial to assess the effectiveness of the MOVI-2
      program on overweight prevention in schoolchildren.
AB  - INTRODUCTION AND OBJECTIVES: The MOVI physical activity program has been shown to
      reduce adiposity and to improve serum lipid profiles in schoolchildren. However,
      MOVI may have not achieved its maximum potential effectiveness, as increased
      physical activity on weekdays may have been offset by more sedentary behavior at
      weekends. We therefore developed the MOVI-2 program, which includes physical
      activity at weekends as well. This paper reports the rationale and methods of a
      trial to assess the effectiveness of MOVI-2 in preventing overweight and reducing
      cardiovascular risk in 1200 4th- and 5th-grade primary schoolchildren in Cuenca,
      Spain. METHODS: Ten schools were randomly assigned to MOVI-2 and 10 schools to
      the control group. MOVI-2 consisted of recreational physical activity in after
      school time, including two 90-min sessions on weekdays and one 150-min session on
      Saturdays, during each week of one academic year. The control group was expected
      to follow their usual patterns of physical activity. The primary end points,
      which were assessed at the start and the end of the MOVI-2 program, were weight
      and height, waist circumference, skinfold thickness, body fat percentage, blood
      pressure, lipid profile, and insulin resistance. Secondary end points were
      physical activity, fitness, health-related quality of life, sleep quality,
      academic performance, enjoyment with physical activity, and physical self
      concept. CONCLUSIONS: This study will assess whether MOVI-2 overcomes some
      potential limitations of physical activity interventions in children
      (Clinicaltrials.gov number NCT01277224).

PMID- 22410390
TI  - Is single-port access laparoscopy less painful than conventional laparoscopy for
      adnexal surgery? A comparison of postoperative pain and surgical outcomes.
AB  - OBJECTIVE: This study aimed to compare postoperative pain and surgical outcomes
      after transumbilical single-port access (SPA) and conventional multiport
      laparoscopic surgery for adnexal lesions. METHODS: A retrospective case-control
      study was conducted matched by age, body mass index, and frequency of previous
      abdominal surgery. A total of 110 SPA laparoscopy patients (cases) were matched
      with a cohort of 107 patients who underwent conventional laparoscopy (controls)
      for benign adnexal lesions. SPA system consisted of a wound retractor, surgical
      glove, two 5-mm trocars, and one 11-mm trocar. Postoperative pain scores were
      measured immediately after surgery and at 6, 24, and 48 hours postsurgery using
      the numerical rating scale. RESULTS: Postoperative pain scores did not differ
      between the 2 groups (P = .552). However, higher number of painkiller
      administrations was observed in the SPA laparoscopy group (median 3 vs 1, P <
      .001). The type of surgery and intraoperative blood loss were the significant
      factors influencing the number of painkiller administrations after controlling
      for other parameters by linear regression (P < .0001). The SPA laparoscopy group
      had less intraoperative blood loss (45.3 vs 87.5 mL, P < .001) and shorter
      hospital stay (2.1 +/- 0.8 vs 2.7 +/- 1.0 days, P < .001) compared with the
      conventional laparoscopy group. Operative time and perioperative complications
      did not differ between groups. CONCLUSIONS: There was no difference in pain
      intensity between the SPA and conventional laparoscopic group in this study.
      Future trials are warranted to better define the benefits of SPA surgery in terms
      of postoperative pain.

PMID- 22410391
TI  - Suprapubic appendectomy: a different single-incision approach.
AB  - INTRODUCTION: Appendectomy is performed on almost 700 000 patients per year in
      the European Community, rendering it the most common acute surgical procedure.
      Since the introduction of laparoscopic surgery, there has been increased interest
      in carrying out procedures with fewer incisions and less ports. MATERIALS AND
      METHODS: After the inception of single-port access, it is possible to insert into
      the abdominal cavity multiple instruments through a single device. A total of 15
      patients--mean age 22 years and mean body mass index 27 kg/m(2)--with acute
      appendicitis were included in this study. RESULTS: Mean operative time was 35
      minutes with no conversions. Local suction drain was needed in 2 patients. Mean
      hospital stay was less than 24 hours with no complications. CONCLUSION: Single
      port suprapubic appendectomy is feasible and safe, and can allow a more direct
      vision of the operating field depending on the position of the appendix and
      presents good cosmetic and postoperative outcomes.

PMID- 22410392
TI  - Fitter, healthier, happier families: a partnership to treat childhood obesity in
      the West Midlands.

PMID- 22410393
TI  - Nucleus accumbens D2- and D1-receptor expressing medium spiny neurons are
      selectively activated by morphine withdrawal and acute morphine, respectively.
AB  - Opioids are effective analgesic agents but serious adverse effects such as
      tolerance and withdrawal contribute to opioid dependence and limit their use.
      Opioid withdrawal involves numerous brain regions and includes suppression of
      dopamine release and activation of neurons in the ventral striatum. By contrast,
      acute opioids increase dopamine release. Like withdrawal, acute opioids also
      activate neurons in the ventral striatum, suggesting that different populations
      of ventral striatal neurons may be activated by withdrawal and acute opioid
      actions. Here, immunofluorescence for the activity-related immediate-early gene,
      c-Fos, was examined in transgenic reporter mouse lines by confocal microscopy to
      study the specific populations of ventral striatal neurons activated by morphine
      withdrawal and acute morphine. After chronic morphine, naloxone-precipitated
      withdrawal strongly increased expression of c-Fos immunoreactivity, predominantly
      in D2-receptor (D2R) medium-sized spiny neurons (MSNs) of the nucleus accumbens
      (NAc) core and shell regions. By contrast, a single injection of morphine
      exclusively activated c-Fos immunoreactivity in D1-receptor expressing (D1R) MSNs
      of the core and shell of the NAc. These results reveal a striking segregation of
      neuronal responses occurring in the two populations of MSNs of the NAc in
      response to morphine withdrawal and acute morphine.

PMID- 22410394
TI  - Should rural Latin America align to the international diabetes rise forecasts?

PMID- 22410395
TI  - DPP-IV inhibitory potential of naringin: an in silico, in vitro and in vivo
      study.
AB  - The incretin based therapies are an emerging class of antidiabetic drugs, with
      two categories: one is glucagone like peptide-1 (GLP-1) agonists and the other
      one is dipeptidyl peptidase (CD26; DPP-IV) inhibitors. However, in the DPP-IV
      inhibitors category only few compounds are commercially available and also have
      some undesirable effects. Therefore, in the present work we tried to explore a
      naturally occurring compound naringin for its potential DPP-IV inhibition and
      antidiabetic potential. It is noteworthy that this compound is abundantly present
      in orange peel and thus may provide cost effective treatment for diabetes,
      especially type 2 diabetes mellitus. In the present study, we have conducted
      virtual docking study and observed tight binding of naringin, as shown by higher
      negative values of H bond lengths, while in vitro DPP-IV inhibition assay has
      also shown better inhibition by naringin. In vivo study, in response to 10 days
      administration of 40 mg/kg of naringin twice daily to Wistar albino rats,
      inhibited the serum levels of DPP-IV activity, random glucose concentration with
      concomitant increase in insulin levels. All the comparisons were made with the
      standard commercially available drug sitagliptin.

PMID- 22410396
TI  - The clinical potential of exhaled breath analysis for diabetes mellitus.
AB  - Various compounds in present human breath have long been loosely associated with
      pathological states (including acetone smell in uncontrolled diabetes). Only
      recently, however, the precise measurement of exhaled volatile organic compounds
      (VOCs) and aerosolized particles was made possible at extremely low
      concentrations by advances in several analytical methodologies, described in
      detail in the international literature and each suitable for specific subsets of
      exhaled compounds. Exhaled gases may be generated endogenously (in the pulmonary
      tract, blood, or peripheral tissues), as metabolic by-products of human cells or
      colonizing micro-organisms, or may be inhaled as atmospheric pollutants; growing
      evidence indicates that several of these molecules have distinct cell-to-cell
      signaling functions. Independent of origin and physiological role, exhaled VOCs
      are attractive candidates as biomarkers of cellular activity/metabolism, and
      could be incorporated in future non-invasive clinical testing devices. Indeed,
      several recent studies reported altered exhaled gas profiles in dysmetabolic
      conditions and relatively accurate predictions of glucose concentrations, at
      least in controlled experimental conditions, for healthy and diabetic subjects
      over a broad range of glycemic values. Optimization of this methodology and
      validation in large-scale trials under a wider range of conditions is needed to
      determine its true potential to transition into practical clinical use.

PMID- 22410397
TI  - Performance of the preliminary classification criteria for cryoglobulinaemic
      vasculitis and clinical manifestations in hepatitis C virus-unrelated
      cryoglobulinaemic vasculitis.
AB  - BACKGROUND: Cryoglobulinaemic vasculitis (CV) is often related to hepatitis C
      virus (HCV) infection, but it can develop in other diseases (e.g. other
      infections, connective tissue diseases, malignancies) in the absence of HCV
      infection. A comparison of the performance of the recently published
      classification criteria for the CV was made between HCV-positive and HCV negative
      patients with serum cryoglobulins. METHODS: 500 patients with serum cryoglobulins
      were studied. Their mean age was 60.77+/-13.75 years, they were 356 females
      (71.2%) and 144 males (28.8%). CV was diagnosed in 272 patients (54.4%), while
      other diseases associated with serum cryoglobulins without CV (CwV) were
      diagnosed in 228 patients (45.6%). RESULTS: 117 HCV negative patients were
      collected (23.4%) and they were 42/272 (15.4%) among the CV group, while they
      were 75/228 (32.9%) among the CwV. In HCV negative patients the sensitivity and
      specificity of the classification criteria of CV were 89.5% CI 95% [79.5-99.5]
      and 90.3% CI 95% [82.8-97.8], respectively, while in HCV positive patients they
      were 88.3% CI 95% [83.6%-93.1%] and 96.1% CI 95% [91.8-100], respectively. The
      most frequent disease recognised among the HCV negative patients was Sjogren's
      syndrome (SS) (55/117, 47.0%), and the sensitivity and the specificity of the CV
      classification criteria were 88.9% CI 95% [76.5-100] and 91.3% CI 95% [79.2-100],
      respectively. CONCLUSIONS: The classification criteria for CV showed a good
      performance even in HCV-unrelated patients. A slightly lower specificity was
      observed for the classification of HCV-unrelated CV, since some clinical
      manifestations included in the clinical item for the classification criteria
      occurred more frequently in HCV-negative rather than HCV-positive controls with
      CWV.

PMID- 22410398
TI  - Enzymolysis kinetics and activities of ACE inhibitory peptides from wheat germ
      protein prepared with SFP ultrasound-assisted processing.
AB  - There is a great demand for developing efficient enzymolysis methods in order to
      increase the enzymolysis efficiencies and activities of angiotensin converting
      enzyme (ACE) inhibitory peptides from wheat germ protein. The enzymolysis
      kinetics, ACE inhibitory activity of peptide and conversion rate of protein were
      studied using sweep frequency and pulsed (SFP) ultrasound-assisted enzymolysis
      and the results were compared with traditional enzymolysis. The studied factors
      were enzymolysis time and substrate concentration. By considering the activity of
      ACE inhibitory peptide and operation cost, the recommended conditions of SFP
      ultrasound-assisted enzymolysis were enzymolysis time of 120 min and substrate
      concentration of 24.0 g/L, which gave high conversion rates of protein (60.7%)
      and ACE inhibitory activity of peptide (65.9%). Compared to traditional
      enzymolysis, SFP ultrasound-assisted enzymolysis significantly increased the
      initial reaction rate (V) by 60.0% at substrate concentration of 24.0 g/L,
      increased the apparent breakdown rate constant (k(A)) by 66.7%, decreased the
      apparent constant (K(M)) by 6.9%, and raised the conversion rate of protein by
      35.5% and ACE inhibitory activity of peptides by 35.6% under the recommended
      conditions. It has been concluded that SFP ultrasound can remarkably raise the
      enzymolysis efficiency and activity of ACE inhibitory peptides from wheat germ
      protein.

PMID- 22410399
TI  - Cavitation assisted delignification of wheat straw: a review.
AB  - Wheat is grown in most of the Indian and Chinese regions and after harvesting,
      the remaining straw offers considerable promise as a renewable source most
      suitable for papermaking and as a pulping resource. Delignification of wheat
      straw offers ample scope for energy conservation by way of the application of the
      process intensification principles. The present work reviews the pretreatment
      techniques available for improving the effectiveness of the conventional approach
      for polysaccharide component separation, softening and delignification. A
      detailed overview of the cavitation assisted delignification process has been
      presented based on the earlier literature illustrations and important operational
      guidelines have been presented for overall low-cost and amenable energy
      utilization in the processes. The effectiveness of the methods has been evaluated
      according to yield and properties of the isolated fibers in comparison to the
      conventional treatment. Also the experimental results of one such non
      conventional treatment scheme based on the use of hydrodynamic cavitation have
      been presented for the pulping of wheat straw. The effect of hydrodynamically
      induced cavitation on cell wall matrix and its components have been characterized
      using FT-IR analysis with an objective of understanding the cavitation assisted
      digestion mechanism on straws. It has been observed that the use of hydrodynamic
      cavitation does not degrade the fibrillar structure of cellulose but causes
      relocalisation and partial removal of lignin. Overall it appears that
      considerable improvement can be obtained due to the use of pretreatment or
      alternate techniques for delignification, which is an energy intensive step in
      the paper making industries.

PMID- 22410400
TI  - Effective screening tool to triage recovery rooms for possible tuberculosis
      patients undergoing bronchoscopy.
AB  - SETTING: In 2005, tuberculin skin test conversions were observed following
      exposure to a patient with active pulmonary tuberculosis (TB) who recovered post
      bronchoscopy in an open area at The Ottawa Hospital, Canada. In response, we
      implemented a screening tool to triage patients to  an airborne infection
      isolation (AII) room pre- and post-bronchoscopy. OBJECTIVE: To evaluate the
      performance of the screening tool in detecting patients with culture-confirmed
      TB. DESIGN: All bronchoscopies performed between 1 March 2006 and 31 March 2010
      were retrospectively reviewed. RESULTS: Of 1839 patients included (55.3% of
      bronchoscopies), 210 screened positive, capturing 28 culture-confirmed TB cases.
      Three patients with positive TB cultures screened negative. The sensitivity of
      the screening tool was 90.3%; the negative predictive value was 99.8%. A positive
      screening result  was strongly predictive of a positive TB culture. CONCLUSIONS:
      The screening tool is effective for identifying high-risk patients and triaging
      them to AII rooms. The pre-bronchoscopy screening tool is simple and inexpensive
      to implement and has the potential to reduce intra-institutional  spread of TB.

PMID- 22410401
TI  - Durability of composite repair using different surface treatments.
AB  - OBJECTIVE: To evaluate the surface treatment and hydrophilicity of the bonding
      agent on the composite repair strength (RS), silver nitrate uptake (SNU), surface
      roughness (SR) and estimation of surface area (SA). METHODS: Fifty resin blocks
      (Opallis, FGM) were polished and divided in 5 groups: no treatment (NT);
      roughening with a fine (FDB); medium (MDB); coarse-grit (CDB) and 50-MUm
      aluminium oxide sandblasting (AO). A hydrophobic (Adhesive, Scotchbond Multi
      Purpose Plus, 3M ESPE) or hydrophilic (Adper Single Bond 2, 3M ESPE) adhesive was
      applied, followed by composite placement (Opallis, FGM). Composite-composite
      bonded sticks (0.9 mm2) were tested in tension (1.0mm/min) immediately [IM] or
      after 6 months [6M] of water storage. Two sticks from each tooth, at each time,
      were immersed in a 50% silver nitrate solution and evaluated by SEM. A
      profilometer was used to measure SR. SEM images were used to estimate the SA
      using the Image J software. Data were analysed by ANOVA and Tukey's tests.
      RESULTS: The AO showed the highest CR strength for both adhesives, whilst the NT
      group showed the lowest, irrespective of the storage period. The diamond burs had
      intermediate performance. Silver nitrate deposits were seen after 6M for the
      hydrophilic adhesive. The ranking of SR values (Ra) from the lowest to the
      highest was: NT<FDB<MDB<AO<=CDB. A higher SA was produced by AO treatment.
      CONCLUSIONS: The AO treatment provides the highest CR strength likely due to the
      high SA produced. The bonding agent did not seem to affect the CR strength after
      6M, although early signs of degradation were detected for the hydrophilic system.
      CLINICAL SIGNIFICANCE: Polished composite should be preferred roughened with
      aluminium oxide followed by the application of a hydrophobic intermediate agent
      before composite repair.

PMID- 22410402
TI  - Association between rs4673 (C/T) and rs13306294 (A/G) haplotypes of NAD(P)H
      oxidase p22phox gene and severity of stenosis in coronary arteries.
AB  - Phagocytic NADH/NADPH oxidase is an important enzyme producing reactive oxygen
      species within subendothelial space of vessels. Findings have shown that p22phox
      subunit is an essential element related to the enzyme activity. Since some
      p22phox polymorphisms are thought to have functional roles in the enzyme thus, we
      studied the association between rs4673 (C242T) and rs13306294 (A/G) haplotypes
      and the severity of stenosis in coronary arteries. One hundred eighty-two
      subjects undergoing coronary angiography were recruited on the base of study
      design. Patients (n=114) had at least a stenosed coronary artery (>50% stenosis)
      and subdivided into three subgroups; SVD (n=28), 2VD (n=31) and 3VD (n=55) while
      controls (n=68) had the normal coronary arteries (<5% stenosis). The direct
      haplotyping technique of SNPs was performed using ARMS-RFLP-PCR method.
      Furthermore, alphabet-based tools predicted the changes of secondary structure at
      the rs4673 position. All haplotypes being proposed theoretically were found in
      the study population. The distribution of two-allele haplotypes had no
      significant difference between patients and controls (P=0.1). Although the rs4673
      allele frequency was not significant between the groups (P>0.5), chi square test
      and multinomial regression analysis showed an observed high risk for rs13306294 A
      allele among patients. The bioinformatics tools predicted that the p22phox
      secondary structure is not changed due to the substitution of Tyr->His at the
      rs4673 position. We concluded that the polymorphisms have no allele linkage on
      the chromosome. In addition, the rs13306294 A allele is a potential factor of
      stenosis of coronary arteries that increases susceptibility for the extent of
      disease.

PMID- 22410403
TI  - Making sense of transcribing chromatin.
AB  - Eukaryotic cells package their genomes into a nucleoprotein form called
      chromatin. The basic unit of chromatin is the nucleosome, formed by the wrapping
      of ~147bp of DNA around an octameric complex of core histones. Advances in
      genomic technologies have enabled the locations of nucleosomes to be mapped
      across genomes. This has revealed a striking organisation with respect to
      transcribed genes in a diverse range of eukaryotes. This consists of a nucleosome
      depleted region upstream of promoters, with an array of well spaced nucleosomes
      extending into coding regions. This observation reinforces the links between
      chromatin organisation and transcription. Central to this is the paradox that
      while chromatin is required by eukaryotes to restrict inappropriate access to
      DNA, this must be overcome in order for genetic information to be expressed. This
      conundrum is at its most flagrant when considering the need for nucleic acid
      polymerase's to transit 1000's of based pairs of DNA wrapped as arrays of
      nucleosomes.

PMID- 22410405
TI  - Establishment of an 11-year cohort of 8733 pediatric patients hospitalized at
      United States free-standing children's hospitals with de novo acute lymphoblastic
      leukemia from health care administrative data.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) accounts for almost one quarter of
      pediatric cancer in the United States. Despite cooperative group therapeutic
      trials, there remains a paucity of large cohort data on which to conduct
      epidemiology and comparative effectiveness research studies. RESEARCH DESIGN: We
      designed a 3-step process utilizing International Classification of Diseases-9
      Clinical Modification (ICD-9) discharge diagnoses codes and chemotherapy exposure
      data contained in the Pediatric Health Information System administrative database
      to establish a cohort of children with de novo ALL. This process was validated by
      chart review at 1 of the pediatric centers. RESULTS: An ALL cohort of 8733
      patients was identified with a sensitivity of 88% [95% confidence interval (CI),
      83%-92%] and a positive predictive value of 93% (95% CI, 89%-96%). The 30-day all
      cause inpatient case fatality rate using this 3-step process was 0.80% (95% CI,
      0.63%-1.01%), which was significantly different than the case fatality rate of
      1.40% (95% CI, 1.23%-1.60%) when ICD-9 codes alone were used. CONCLUSIONS: This
      is the first report of assembly and validation of a cohort of de novo ALL
      patients from a database representative of free-standing children's hospitals
      across the United States. Our data demonstrate that the use of ICD-9 codes alone
      to establish cohorts will lead to substantial patient misclassification and
      result in biased outcome estimates. Systematic methods beyond the use of just ICD
      9 codes must be used before analysis to establish accurate cohorts of patients
      with malignancy. A similar approach should be followed when establishing future
      cohorts from administrative data.

PMID- 22410406
TI  - Disparities in receipt of antiretroviral therapy among HIV-infected adults (2002
      2008).
AB  - OBJECTIVE: Prior research has documented sociodemographic disparities in the use
      of antiretroviral therapy (ART). Recent therapeutic developments and changing
      epidemiological profiles may have altered such disparities. We examine the extent
      to which sociodemographic differences in prescribed ART have changed between 2002
      and 2008. METHODS: We analyzed data abstracted from medical records at 13 US
      sites participating in the Human Immunodeficiency Virus Research Network.
      Prescription of ART was assessed for each year in care for each patient. A total
      of 14,092 patients were followed up for 39,251 person-years. We examined ART use
      as a function of sex, race/ethnicity, human immunodeficiency virus risk group,
      age, and CD4 history (no test <500 cells/mm, one or more tests between 500 and
      350 cells/mm, 1 test <=350 cells/mm, and 2 or more tests <=350 cells/mm). Using
      multiple logistic regression, we ascertained interactions between each of these
      variables and calendar year. RESULTS: The overall percentage prescribed ART
      increased from 60% to 80% between 2002 and 2008. Among those with 2 or more CD4
      tests <=350 cells/mm, the percentage increased from 82% to 92%. ART rates were
      higher for those with lower CD4 counts but increased over time for all CD4 groups
      and for all demographic groups. Nevertheless, sex and racial/ethnic disparities
      persisted. Significant interactions were obtained for CD4 history by year, age by
      year, and age by CD4 history. CONCLUSIONS: Although prescription of ART became
      more widespread from 2002 to 2008, patients who were female, black, or younger
      still had lower ART rates than male, white, or older patients.

PMID- 22410407
TI  - Forecasting lifetime and aggregate long-term care spending: accounting for
      changing disability patterns.
AB  - OBJECTIVE: The impact population aging exerts on future levels of long-term care
      (LTC) spending is an urgent topic in which few studies have accounted for
      disability trends. We forecast individual lifetime and population aggregate
      annual LTC spending for the Dutch 55+ population to 2030 accounting for changing
      disability patterns. METHODS: Three levels of (dis)ability were distinguished:
      none, mild, and severe. Two-part models were used to estimate LTC spending as a
      function of age, sex, and disability status. A multistate life table model was
      used to forecast age-specific prevalence of disability and life expectancy (LE)
      in each disability state. Finally, 2-part model estimates and multistate
      projections were combined to obtain forecasts of LTC expenditures. RESULTS: LE is
      expected to increase, whereas life years in severe disability remain constant,
      resulting in a relative compression of severe disability. Mild disability life
      years increase, especially for women. Lifetime homecare spending--mainly
      determined by mild disability--increases, whereas institutional spending remains
      fairly constant due to stable LE with severe disability. Lifetime LTC
      expenditures, largely determined by institutional spending, are thus hardly
      influenced by increasing LE. Aggregate spending for the 55+ population is
      expected to rise by 56.0% in the period of 2007-2030. CONCLUSIONS: Longevity
      gains accompanied by a compression of severe disability will not seriously
      increase lifetime spending. The growth of the elderly cohort, however, will
      considerably increase aggregate spending. Stimulating a compression of disability
      is among the main solutions to alleviate the consequences of longevity gains and
      population aging to growth of LTC spending.

PMID- 22410408
TI  - Doctor and pharmacy shopping for controlled substances.
AB  - BACKGROUND: Prescription drug abuse is a major health concern nationwide, with
      West Virginia having one of the highest prescription drug death rates in the
      United States. Studies are lacking that compare living subjects with persons who
      died from drug overdose for evidence of doctor and pharmacy shopping for
      controlled substances. The study objectives were to compare deceased and living
      subjects in West Virginia for evidence of prior doctor and pharmacy shopping for
      controlled substances and to identify factors associated with drug-related death.
      METHODS: A secondary data study was conducted using controlled substance,
      Schedule II-IV, prescription data from the West Virginia Controlled Substance
      Monitoring Program and drug-related death data compiled by the Forensic Drug
      Database between July 2005 and December 2007. A case-control design compared
      deceased subjects 18 years and older whose death was drug related with living
      subjects for prior doctor and pharmacy shopping. Logistic regression identified
      factors related to the odds of drug-related death. RESULTS: A significantly
      greater proportion of deceased subjects were doctor shoppers (25.21% vs. 3.58%)
      and pharmacy shoppers (17.48% vs. 1.30%) than living subjects. Approximately
      20.23% of doctor shoppers were also pharmacy shoppers, and 55.60% of pharmacy
      shoppers were doctor shoppers. Younger age, greater number of prescriptions
      dispensed, exposure to opioids and benzodiazepines, and doctor and pharmacy
      shopping were factors with greater odds of drug-related death. CONCLUSIONS:
      Doctor and pharmacy shopping involving controlled substances were identified, and
      shopping behavior was associated with drug-related death. Prescription monitoring
      programs may be useful in identifying potential shoppers at the point of care.

PMID- 22410409
TI  - Comparison of complication rates in veterans receiving cataract surgery through
      the Veterans Health Administration and Medicare.
AB  - BACKGROUND: To compare the 90-day rates of select secondary procedures after
      cataract extraction in patients having fee-for-service surgery under Medicare to
      surgeries provided through the Veterans Health Administration (VHA) during the
      same calendar year. METHODS: Medicare, VHA, and VHA Fee Basis Program data for
      calendar year 2007 were merged to identify a cohort of veterans that had
      outpatient cataract surgery. Secondary surgeries were tracked using selected
      Current Procedural Terminology (CPT) codes as surrogate markers for
      complications. Primary surgery and corrective surgeries were linked through right
      and left eye CPT modifier codes. Risks of complications were adjusted for race,
      age, sex, and ocular and medical comorbidities. RESULTS: A total of 223,873
      cataract extractions were performed on veterans during calendar year 2007, 88.4%
      of which were provided through Medicare. The 90-day overall rate of CPT-coded
      secondary procedures was greater for patients having cataract surgery through the
      VHA (37.2 per 1000 surgeries) than Medicare (18.2 per 1000 surgeries). The
      overall rate was influenced primarily by higher rates of vitrectomy and related
      procedures, after both routine and complex cataract extractions. The adjusted
      odds ratio of vitrectomy within 90 days of routine cataract surgery in the VHA
      with reference to Medicare was 3.77 (95% confidence interval, 3.44-4.14).
      CONCLUSIONS: In 2007, the pattern and rates of secondary surgeries after cataract
      extraction varied between the Medicare and the VHA programs. If these results are
      confirmed, further research to identify the sources of higher secondary procedure
      rates is warranted to enhance patient safety.

PMID- 22410410
TI  - The hospital standardized mortality ratio fallacy: a narrative review.
AB  - BACKGROUND: Outcome measures, like hospital standardized mortality ratios
      (HSMRs), are increasingly used to assess quality of care. The validity of HSMRs
      and their accuracy to reflect quality of care is heavily contested. OBJECTIVE: We
      explored apparent and potential shortcomings and adverse effects of the HSMR in
      the assessment of quality of care. RESEARCH DESIGN AND METHODS: For this
      narrative review, relevant articles were collected from Medline databases using
      the following search terms: "hospital standardized mortality ratio,"
      "standardized mortality ratio," "HSMR," "quality of care," and "in-hospital
      mortality." In addition, other important articles were subtracted from the
      reference lists of the primary articles. RESULTS: The current literature exhibits
      important shortcomings of the HSMR that in particular affect hospitals providing
      specialized care of a certain level of complexity. Because of the lack or
      insufficiency of data concerning case-mix, coding variation between hospitals,
      disease severity, referral bias, end-of-life care, and place of death, the
      current HSMR model is not able to adjust adequately for these aspects. This leads
      to incomparability of HSMRs between hospitals. Instead of separate aspects of
      continuity of care, all factors contributing to quality of care should be
      considered. CONCLUSIONS: Given the several shortcomings, use of the HSMR as an
      indicator of quality of care can be considered as a fallacy. Publication of the
      HSMR is not likely to lead to improvement of quality of care and might harm both
      hospitals and patients.

PMID- 22410412
TI  - Effective factors on linguistic disorder during acute phase following traumatic
      brain injury in adults.
AB  - Traumatic brain injury (TBI) has been known to be the leading cause of breakdown
      and long-term disability in people under 45 years of age. This study highlights
      the effective factors on post-traumatic (PT) linguistic disorder and relations
      between linguistic and cognitive function after trauma in adults with acute TBI.
      A cross-sectional design was employed to study 60 post-TBI hospitalized adults
      aged 18-65 years. Post-traumatic (PT) linguistic disorder and cognitive deficit
      after TBI were respectively diagnosed using the Persian Aphasia Test (PAT) and
      Persian version of Mini-Mental State Examination (MMSE) at discharge. Primary
      post-resuscitation consciousness level was determined using the Glasgow Coma
      Scale (GCS). Paracilinical data was obtained by CT scan technique. Multiple
      logistic regression analysis illustrated that brain injury severity was the first
      powerful significant predictor of PT linguistic disorder after TBI and
      frontotemporal lesion was the second. It was also revealed that cognitive
      function score was significantly correlated with score of each language skill
      except repetition. Subsequences of TBI are more commonly language dysfunctions
      that demand cognitive flexibility. Moderate, severe and fronto-temporal lesion
      can increase the risk of processing deficit in linguistic macrostructure
      production and comprehension. The dissociation risk of cortical and subcortical
      pathways related to cognitive-linguistic processing due to intracranial lesions
      can augment possibility of lexical-semantic processing deficit in acute phase
      which probably contributes to later cognitive-communication disorder.

PMID- 22410411
TI  - Sensitivity of Medicare claims data for measuring use of standard multiagent
      chemotherapy regimens.
AB  - PURPOSE: We sought to determine the accuracy with which Medicare billing data
      documents elderly Medicare cancer patients' receipt of common multiagent
      chemotherapy regimens. METHODS: We merged gold-standard clinical trial data from
      406 elderly cancer patients known to be treated on 1 of 6 Cancer and Leukemia
      Group B (CALGB) breast, colorectal, and lung cancer trials (trial numbers; 9344,
      9730, 9235,9732, 80203, 89803) with their Medicare claims data from Centers for
      Medicare and Medicaid Services (CMS). Comparing CMS chemotherapy codes to gold
      standard CALGB treatment data, we estimated Medicare data's sensitivity at
      measuring the correct drugs and schedule for each of the multiagent chemotherapy
      regimens. RESULTS: Overall 92% (375/406) of CALGB patients had contemporaneous
      CMS claims indicating receipt of chemotherapy. The overall sensitivity of CMS
      ambulatory claims for documenting treatment with the correct drugs and on the
      correct schedule (ie, all drugs had to be billed on the same day) for the 5
      common multiagent chemotherapy regimens was 78% (275/354) for those potentially
      treated in the ambulatory setting. The sensitivity was similar for all treatment
      regimens: carboplatin and paclitaxel 83%, 5-fluorouracil and leucovorin 80%,
      fluorouracil, leucovorin, and irinotecan (FOLFIRI) 76%, doxorubicin and
      cyclophosphamide 75%, and cisplatin and etoposide 75%. CONCLUSIONS: We correctly
      identified at least 3-quarters of elderly Medicare cancer patients treated on a
      clinical trial with standard first-line multiagent chemotherapy regimens in the
      ambulatory setting by applying coding algorithms to their CMS claims. The
      algorithms may be useful in identifying cohorts of elderly Medicare patients for
      observational studies of the comparative effectiveness of standard multiagent
      chemotherapy regimens.

PMID- 22410413
TI  - Electrophysiological evidence for a multisensory speech-specific mode of
      perception.
AB  - We investigated whether the interpretation of auditory stimuli as speech or non
      speech affects audiovisual (AV) speech integration at the neural level.
      Perceptually ambiguous sine-wave replicas (SWS) of natural speech were presented
      to listeners who were either in 'speech mode' or 'non-speech mode'. At the
      behavioral level, incongruent lipread information led to an illusory change of
      the sound only for listeners in speech mode. The neural correlates of this
      illusory change were examined in an audiovisual mismatch negativity (MMN)
      paradigm with SWS sounds. In an oddball sequence, 'standards' consisted of
      SWS/onso/coupled with lipread/onso/, and 'deviants' consisted of SWS/onso/coupled
      with lipread/omso/. The AV deviant induced a McGurk-MMN for listeners in speech
      mode, but not for listeners in non-speech mode. These results demonstrate that
      the illusory change in the sound by incongruent lipread information evoked an MMN
      which presumably takes place at a pre-attentive sensory processing stage.

PMID- 22410414
TI  - The timing of individual face recognition in the brain.
AB  - Previous neural research on face perception has mainly focused on the distinction
      between faces and non-face stimuli. However, the brain mechanisms for
      differentiating one face from another are not well understood. In the present
      study, using scalp-recorded event-related potentials (ERPs), we investigated the
      brain responses to faces that varied in identity strength as a result of morphing
      individual faces to an "average" face in steps of 10%. Participants performed a
      face identification task. Behavioral results showed categorical boundaries of
      face identification at 30% and 70%. Face identity strength related to initial
      brain responses occurring shortly after 200 ms in the ventral P2 and the N250
      components: stronger identity strength was associated with a smaller P2 and a
      larger N250. In contrast, the brain responses within 200 ms, as reflected by the
      P1, the N170, and the dorsal P2 component, were not affected by face identity
      strength. Consistent with recent imaging studies and animal research, our results
      provide the ERP evidence for brain responses to variations in face identity
      strength relative to an "average" face. Furthermore, with the high temporal
      resolution of ERPs, our results help to clarify the timing of neural events that
      are associated with the different stages involved in recognizing individual
      faces, thus providing a timeline for the classical face recognition model in the
      brain.

PMID- 22410415
TI  - Survival of HIV-infected patients after starting tuberculosis treatment: a
      prospective cohort study.
AB  - OBJECTIVES: To estimate the probability of survival and to evaluate risk factors
      for death in a cohort of persons living with human immunodeficiency virus (PLHIV)
      who had started tuberculosis (TB) treatment. METHODS: A prospective cohort study
      was conducted between June 2007 and December 2009 with HIV-infected patients who
      had started anti-tuberculosis treatment in the State of Pernambuco, Brazil.
      Survival data were analysed using the Kaplan-Meier estimator, the log-rank test
      and the Cox model. Hazard ratios and their respective 95%CIs were estimated.
      RESULTS: Of a cohort of 2310 HIV-positive individuals, 333 patients who had
      commenced treatment for TB were analysed. The mortality rate was 5.25 per 10,000
      person-years (95%CI 4.15-6.63). The probability of survival at 30 months was 74%.
      Risk factors for death in the study population were being female, age >=30 years,
      having anaemia, not using highly active antiretroviral therapy (HAART) during
      treatment for TB and disseminated TB. Protective factors for death were a CD4
      lymphocyte count >200 cells/mm(3) and treatment for TB having started in an out
      patient clinic. CONCLUSIONS: The use of HAART can prevent deaths among HIV-TB
      patients, corroborating the efficacy of starting HAART early in individuals with
      TB.

PMID- 22410416
TI  - Correlation between chemical composition and antibacterial activity of essential
      oils from fifteen Eucalyptus species growing in the Korbous and Jbel Abderrahman
      arboreta (North East Tunisia).
AB  - The essential oils of fifteen Eucalyptus species harvested from the Jbel
      Abderrahman and Korbous arboreta (North East Tunisia) were screened for their
      antibacterial activities by the agar disc diffusion method. Eighteen major
      components as identified by GC/FID and GC/MS were selected for a study of the
      chemical and biological activity variability. The main one was 1,8-cineole,
      followed by spathulenol, trans-pinocarveol, alpha-pinene, p-cymene, globulol,
      cryptone, beta-phellandrene, viridiflorol, borneol, limonene and isospathulenol.
      The chemical principal component analysis identified five species groups and
      subgroups, where each group constituted a chemotype, however that of the values
      of zone diameter of the inhibition (zdi) identified six groups of Eucalyptus
      oils, characterized by their antibacterial inhibition ability. The strongest
      activity was shown by E. platypus oil against Enterococcus faecalis and by E.
      lamannii oil against Staphylococcus aureus, Pseudomonas aeruginosa and
      Escherichia coli. A correlation between the levels of some major components and
      the antibacterial activities was observed.

PMID- 22410417
TI  - Synthesis of amino core compounds of galactosyl phytosyl ceramide analogs for
      developing iNKT-cell inducers.
AB  - 1-Aminophytosphingosine and 6-aminogalactosyl phytosphingosine were prepared in
      61% and 40% yield libraries with 44 carboxylic acids showed that a 4-butylbenzoic
      acid-derived product exe, respectively. Glycosylation using benzoyl-protected
      lipid resulted in better a-selectivity for ceramide analogs, but the yield was
      less than that obtained with benzyl moieties. Screening the amide rted less
      cytotoxicity. These analogs were purified for validation of immunological
      potencies and the a-GalCer analog but not the sphingosine analog stimulated human
      iNKT cell population.

PMID- 22410418
TI  - Anti-acetylcholinesterase and antioxidant activity of essential oils from
      Hedychium gardnerianum Sheppard ex Ker-Gawl.
AB  - Acetylcholinesterase inhibition, antioxidant and cytotoxic activities of
      Hedychium gardnerianum leaf essential oils from S. Miguel Island were determined.
      All the oils inhibited acetylcholinesterase, with IC(50) values of approximately
      1 mg/mL, showing no statistical differences between collection sites. Three oils
      presented mixed inhibition, whilst one was almost truly competitive. This
      activity can be attributed to the presence of sesquiterpenes, which constituted
      more than 60% of the composition of the oils. Regarding the antioxidant activity
      as measured by the DPPH method, all the oils presented activities similar to
      reference compounds, although with statistical differences between collection
      sites. Cytotoxicity measured using Artemia salina classified these oils as
      moderately toxic, with LC(50) values ranging from 300 to 500 ug/mL. These results
      indicate a possible application of these oils in aromatherapy as coadjuvants in
      the treatment of cognitive diseases such as Alzheimer, since they may contribute
      to increase acetylcholine in cholinergic neurons and simultaneously fight
      deleterious oxidations responsible by neurological degeneration.

PMID- 22410419
TI  - Profiling of phenolic compounds and antioxidant activity of dry extracts from the
      selected Sorbus species.
AB  - The antioxidant efficiency of dry extracts from inflorescences and/or leaves of
      seven Sorbus species was studied using four in vitro tests of SET (single
      electron transfer) and HAT-type (hydrogen atom transfer) mechanisms. The 70%
      methanol extracts and its diethyl ether, ethyl acetate, n-butanol and water
      fractions were tested in parallel with the phenolic standards, e.g., caffeic
      acid, quercetin, BHA, BHT, and Trolox. The SET-type activity of the extracts
      depended primarily on the extraction solvent. The most valuable extracts were n
      butanol and ethyl acetate ones, which activity was high in the DPPH (EC(50) = 3.2
      5.2 MUg/mL), TEAC (2.8-4.0 mmol Trolox/g), and FRAP (9.8-13.7 mmol Fe2+/g) tests,
      and strongly correlated with the total phenolic levels (39.6-58.2% of gallic acid
      equivalents). The HPLC-PDA analysis of the extracts led to the identification of
      chlorogenic acid, isoquercitrin, hyperoside, rutin, quercetin 3-O-sophoroside,
      and sexangularetin 3-O-beta-D-glucopyranoside as the main components. Apart from
      flavonoids and hydroxycinnamic acids, proanthocyanidins have also a significant
      impact on the SET-type activity. The HAT-reactivity of the extracts in the
      linoleic acid peroxidation test (IC(50) = 36.9-228.3 MUg/mL) depended more
      strongly on the plant tissue than on the extraction solvent, and its correlation
      with the phenolic content was weak. Both SET and HAT-type activity of the most
      potent Sorbus extracts was comparable with the activity of the standards,
      indicating their great potential as effective sources for health products.

PMID- 22410420
TI  - Use of spectroscopic, zeta potential and molecular dynamic techniques to study
      the interaction between human holo-transferrin and two antagonist drugs:
      comparison of binary and ternary systems.
AB  - For the first time, the binding of ropinirole hydrochloride (ROP) and aspirin
      (ASA) to human holo-transferrin (hTf) has been investigated by spectroscopic
      approaches (fluorescence quenching, synchronous fluorescence, time-resolved
      fluorescence, three-dimensional fluorescence, UV-vis absorption, circular
      dichroism, resonance light scattering), as well as zeta potential and molecular
      modeling techniques, under simulated physiological conditions. Fluorescence
      analysis was used to estimate the effect of the ROP and ASA drugs on the
      fluorescence of hTf as well as to define the binding and quenching properties of
      binary and ternary complexes. The synchronized fluorescence and three-dimensional
      fluorescence spectra demonstrated some micro-environmental and conformational
      changes around the Trp and Tyr residues with a faint red shift. Thermodynamic
      analysis displayed the van der Waals forces and hydrogen bonds interactions are
      the major acting forces in stabilizing the complexes. Steady-state and time
      resolved fluorescence data revealed that the fluorescence quenching of complexes
      are static mechanism. The effect of the drugs aggregating on the hTf resulted in
      an enhancement of the resonance light scattering (RLS) intensity. The average
      binding distance between were computed according to the forster non-radiation
      energy transfer theory. The circular dichroism (CD) spectral examinations
      indicated that the binding of the drugs induced a conformational change of hTf.
      Measurements of the zeta potential indicated that the combination of
      electrostatic and hydrophobic interactions between ROP, ASA and hTf formed
      micelle-like clusters. The molecular modeling confirmed the experimental results.
      This study is expected to provide important insight into the interaction of hTf
      with ROP and ASA to use in various toxicological and therapeutic processes.

PMID- 22410421
TI  - Hydrolysis of ibuprofen nitrile and ibuprofen amide and deracemisation of
      ibuprofen using Nocardia corallina B-276.
AB  - A novel application of whole cells of Nocardia corallina B-276 for the
      deracemisation of ibuprofen is reported. This microorganism successfully
      hydrolysed ibuprofen nitrile to ibuprofen amide, and ibuprofen amide to
      ibuprofen, using a suspension of cells in a potassium phosphate buffer solution
      (0.1 M, pH = 7.0). These results can be explained by the presence of NHase and
      amidase enzymes, but the reactions are not enantioselective and low ee values
      were obtained. However, (R)-ibuprofen was isolated with > 99% ee by a
      deracemisation process catalysed by N. corallina B-276. This is the first report
      of this kind of catalysis with this microorganism.

PMID- 22410422
TI  - Inhibitory effect of Astragalus polysaccharides on lipopolysaccharide-induced TNF
      a and IL-1beta production in THP-1 cells.
AB  - Astragalus polysaccharides (APS), one of main bioactive components in Astragalus
      membranaceus Bunge, has been reported to possess anti-inflammatory activities,
      but the molecular mechanisms behind this activity are largely unknown. This study
      aimed to investigate expression of inflammatory cytokines and the MAPK/NF-kappaB
      pathway in human THP-1 macrophages induced by lipopolysaccharide (LPS). The
      results showed that the concentrations of TNF-a and IL-1beta released from LPS
      stimulated THP-1 cells increased significantly compared to control (p < 0.01).
      After treatment with APS, the TNF-a and IL-1beta levels were significantly lower
      than those in the LPS group (p < 0.05). The mRNA expression of TNF-a and IL-1beta
      were also inhibited. Mechanistic studies indicated that APS strongly suppressed
      NF-kappaB activation and down-regulated the phosphorylation of ERK and JNK, which
      are important signaling pathways involved in the production of TNF-a and IL
      1beta, demonstrating that APS could suppress the production of TNF-a and IL-1beta
      by LPS stimulated macrophages by inhibiting NF-kappaB activation and ERK and JNK
      phosphorylation.

PMID- 22410423
TI  - Health behaviors associated with use of body building, weight loss, and
      performance enhancing supplements.
AB  - PURPOSE: To identify health-related behaviors associated with potentially harmful
      dietary supplements (DS) - body building (BB), weight loss (WL) and performance
      enhancing (PE), explore common reasons and sources of information for DS use.
      METHODS: Based on the 2005 Survey of 16,146 U.S. military personnel, BB users
      were dichotomized as yes (regular use - taking any supplement of BB at least once
      a week in past 12 months) or no; similarly defined for WL and PE. Weighted
      logistic regression models are used. RESULTS: BB, WL and PE were used by 19.4%,
      17.0%, and 8.0% of participants, respectively. Significantly more users were
      overweight or obese: BMI >=25 (vs. BMI<25); heavy drinkers (vs. abstainers); and
      users of taking steroids in their lifetime (vs. not). Most common reasons of BB,
      WL, and PE users wanted to increase muscle mass, lose weight, and improve
      physical performance (BB: 45.8%, WL: 54.8%, PE: 38.5%). Fewer than 30% discussed
      dietary supplements use with their healthcare providers. The leading source of
      dietary supplements information (BB: 27.8%, WL: 23.6%, PE: 30.0%) was magazines.
      CONCLUSIONS: The dietary supplements: BB, WL and PE were used by significant
      proportions of service members, and associated with risk-taking behaviors that
      may affect overall military readiness and public health.

PMID- 22410424
TI  - Graphene quantum dots: emergent nanolights for bioimaging, sensors, catalysis and
      photovoltaic devices.
AB  - Similar to the popular older cousins, luminescent carbon dots (C-dots), graphene
      quantum dots or graphene quantum discs (GQDs) have generated enormous excitement
      because of their superiority in chemical inertness, biocompatibility and low
      toxicity. Besides, GQDs, consisting of a single atomic layer of nano-sized
      graphite, have the excellent performances of graphene, such as high surface area,
      large diameter and better surface grafting using pi-pi conjugation and surface
      groups. Because of the structure of graphene, GQDs have some other special
      physical properties. Therefore, studies on GQDs in aspects of chemistry,
      physical, materials, biology and interdisciplinary science have been in full flow
      in the past decade. In this Feature Article, recent developments in preparation
      of GQDs are discussed, focusing on the main two approaches (top-down and bottom
      down). Emphasis is given to their future and potential development in bioimaging,
      electrochemical biosensors and catalysis, and specifically in photovoltaic
      devices that can solve increasingly serious energy problems.

PMID- 22410425
TI  - Performance of the Emit(r) II Plus 6-Acetylmorphine Assay on the Viva-E(r)
      analyzer.
AB  - We evaluated the performance of Emit((r)) II Plus 6-Acetylmorphine Assay for
      human urine screening on the Viva-E((r)) analyzer. Precision was evaluated using
      the cutoff and +/-25% controls. Recovery and linearity were studied by spiking 6
      acetylmorphine (6-AM) into human urine pools. Accuracy was evaluated using urine
      specimens and the results were compared to those from GC/MS. Cross-reactivity
      with structurally related drugs was assessed at different cross-reactant
      concentrations. Interferences were assessed in the presence of 7.5 and 12.5 ng/mL
      of 6-AM. The qualitative repeatability coefficients of variation (CV's) ranged
      from 0.3% to 0.4% and the within-lab CV's ranged from 2.0% to 2.2%. In analyte
      units (ng/mL), the repeatability CV's ranged from 1.3% to 2.2% and the within-lab
      CV's ranged from 2.6% to 4.3%. The limit of detection of the assay was found to
      be 2.1 ng/mL. Recovery was within 15% of expected value. Linearity was 2.1-20
      ng/mL. Method comparison showed 99% agreement with GC/MS. The assay had minimal
      cross-reactivity with morphine, morphine-3-glucuronide, morphine-6-glucuronide
      and other opioids. No interference was observed with endogenous interferences and
      structurally unrelated drugs. The assay correctly classified CAP survey samples.
      The Emit((r)) II Plus 6-Acetylmorphine Assay will be a suitable screening method
      for urine specimens in both qualitative and semi-quantitative analyses.

PMID- 22410426
TI  - Survey of pre-hospital therapeutic hypothermia use in France.

PMID- 22410427
TI  - Empirical hospital and professional charges for patient care associated with out
      of hospital cardiac arrest before and after implementation of therapeutic
      hypothermia for comatose survivors.
AB  - OBJECTIVE: The objectives of this study are to characterize the total hospital
      and professional charges for patients with out of hospital cardiac arrest both
      with and without therapeutic hypothermia treatment. METHODS: Retrospective cohort
      study of all adult patients with non-traumatic out of hospital cardiac arrest
      brought to the ED of a single tertiary care hospital over 20 months preceding and
      20 months following implementation of therapeutic hypothermia for comatose
      survivors. Billing and clinical data were obtained from administrative databases
      and the electronic medical record using explicit audited abstraction.
      Demographic, payer characteristics, median charges and reimbursements with
      interquartile ranges are described before and after implementation, stratified by
      patient outcome. RESULTS: Two hundred and twenty-three patients met study
      criteria. The median charge was $3,112 among the 135 patients (60.5%) that did
      not survive to admission and $94,916 among the 88 (39.5%) that did. Median
      charges before and after implementation of therapeutic hypothermia were $6,324
      and $15,537 respectively. Medicare was the most frequent payer. Good neurological
      outcome occurred in 11/115 patients (9.6%) prior to implementation and 22/108
      patients (20.4%) after. Among 23 patients treated with hypothermia, good
      neurological outcome occurred in 11 patients (47.8%). Good neurological outcome
      and treatment with hypothermia were associated with increased procedure
      utilization and higher charges. CONCLUSION: Empirical patient level data confirm
      that charges for patients with out of hospital cardiac arrest are substantial,
      even among patients that do not survive to hospital admission. Treatment with
      therapeutic hypothermia is associated with better outcomes, more procedures, and
      higher charges.

PMID- 22410428
TI  - Obesity: GPR120 dysfunction can cause obesity in mice and humans.

PMID- 22410429
TI  - IBD: IBD specialists identify ten top priorities for comparative effectiveness
      research.

PMID- 22410430
TI  - Hepatitis B: telbivudine protects infants.

PMID- 22410431
TI  - Potential value of nutrigenomics in Crohn's disease.
AB  - Crohn's disease is a chronic relapsing condition that has no certain cure. Both
      genetic susceptibility and nutrition have key roles, but their level of
      involvement varies between patients. Interacting gene pathways influence the
      probability of disease development, but these are affected by stress and various
      environmental factors, including diet. In addition, the role of the gut
      microbiome must not be underestimated, as it is substantially altered in patients
      with Crohn's disease. Although an elemental diet might lead to disease remission,
      reintroducing real foods and sustainable diets in patients with Crohn's disease
      is currently difficult, and would benefit from the sensitivity and rapid feedback
      provided by the field of nutrigenomics. Nutrigenomics utilizes high-throughput
      genomics technologies to reveal changes in gene and protein expression that are
      modulated by the patient's nutrition. The most widely used technique thus far is
      transcriptomics, which permits measurement of changes in the expression of
      thousands of genes simultaneously in one sample. Given the volume of numbers
      generated in such studies, data-basing and bioinformatics are essential to ensure
      the correct application of nutrigenomics at the population level. These methods
      have been successfully applied to animal models of Crohn's disease, and the time
      is right to move them to human studies.

PMID- 22410432
TI  - The effect of task in deaf readers' graphophonological processes: a longitudinal
      study.
AB  - This article reports on an investigation of graphophonological processes in deaf
      readers of French over a 1-year period. Deaf readers are known to have a
      phonological deficit compared to hearing peers, and conclusions from studies on
      this question are often conflicting. Among the different types of phonological
      processing, we can identify graphophonological processes based on correspondences
      between the oral and the written language. In this investigation, we evaluated
      graphophonemic and graphosyllabic processes using, in each case, two different
      tasks varying in their degree of cognitive constraints (CC- vs. CC+). Nineteen 11
      year-old deaf students were compared to younger normal readers of the same
      reading level (RA, n = 17) and to normal readers of the same age (CA, n = 20).
      Two variables were considered in the analyses: accuracy and response latency.
      Results show that deaf readers do process written items at the graphophonological
      level and that graphophonological processes are related to reading ability. Also,
      results indicate main effects of task (CC- vs. CC+), time (T1 vs. T2), and group.
      In general, deaf participants' performances are comparable to those of RA and
      differ from those of CA. Results are discussed within the framework of the study
      of phonology in deaf readers and its relation to reading acquisition.

PMID- 22410434
TI  - Hemodynamics of small aneurysm pairs at the internal carotid artery.
AB  - Cerebral aneurysms carry significant risks because rupture-related subarachnoid
      hemorrhage leads to serious and often fatal consequences. The rupture risk
      increases considerably for multiple aneurysms. Multiple aneurysms can grow from
      the same location of an artery, and the interaction between these aneurysms
      raises the rupture risk even higher. Four aneurysm pair cases at the internal
      carotid artery are investigated for their hemodynamic behaviors using patient
      specific modeling. For each case, aneurysms are separated from the parent artery
      and three models are reconstructed, one with two aneurysms and the other two
      models with only one of the two aneurysms. Results show that the relative
      anatomic location of one aneurysm to the other may determine the hemodynamic
      environment of an aneurysm. The presence of a proximal aneurysm reduces the intra
      aneurysmal flow into the distal aneurysm; the proximal aneurysm and larger
      aneurysm have a greater area under low wall shear stress. The average intra
      aneurysmal inflow ratio ranges from 16% to 41%, and reduction of the inflow ratio
      by an aneurysm pair varies from 6% to 15%. The maximum wall shear stress
      increases for serial aneurysms, but decreases for parallel aneurysms. Interaction
      between parallel aneurysms is not significant; however, the proximal aneurysm in
      serial aneurysms may be subject to a greater rupture risk.

PMID- 22410433
TI  - Regulation of p53: a collaboration between Mdm2 and Mdmx.
AB  - p53 plays an important role in the regulation of the cell cycle, DNA repair, and
      apoptosis and is an attractive cancer therapeutic target. Mdm2 and Mdmx are
      recognized as the main p53 negative regulators. Although it remains unclear why
      Mdm2 and Mdmx are both required for p53 degradation, a model has been proposed
      whereby these two proteins function independent of one another; Mdm2 acts as an
      E3 ubiquitin ligase that catalyzes the ubiquitination of p53 for degradation,
      whereas Mdmx inhibits p53 by binding to and masking the transcriptional
      activation domain of p53, without causing its degradation. However, Mdm2 and Mdmx
      have been shown to function collaboratively. In fact, recent studies have pointed
      to a more important role for an Mdm2/Mdmx co-regulatory mechanism of p53
      regulation than previously thought. In this review, we summarize current progress
      in the field about the functional and physical interaction between Mdm2 and Mdmx,
      their individual and collaborative roles in controlling p53, and inhibitors that
      target Mdm2 and Mdmx as a novel class of anticancer therapeutics.

PMID- 22410435
TI  - Correlation analysis between sulphate content and leaching of sulphates in
      recycled aggregates from construction and demolition wastes.
AB  - In some recycled aggregates applications, such as component of new concrete or
      roads, the total content of soluble sulphates should be measured and controlled.
      Restrictions are usually motivated by the resistance or stability of the new
      structure, and in most cases, structural concerns can be remedied by the use of
      techniques such as sulphur-resistant cements. However, environmental risk
      assessment from recycling and reuse construction products is often forgotten. The
      purpose of this study is to analyse the content of soluble sulphate on eleven
      recycled aggregates and six samples prepared in laboratory by the addition of
      different gypsum percentages. As points of reference, two natural aggregates were
      tested. An analysis of the content of the leachable amount of heavy metals
      regulated by European regulation was included. As a result, the correlation
      between solubility and leachability data allow suggest a limiting gypsum amount
      of 4.4% on recycled aggregates. This limit satisfies EU Landfill Directive
      criteria, which is currently used as reference by public Spanish Government for
      recycled aggregates in construction works.

PMID- 22410436
TI  - Hepatotoxicity during treatment for multidrug-resistant tuberculosis: occurrence,
      management and outcome.
AB  - SETTING: Multidrug-resistant tuberculosis (MDR-TB) treatment program in Tomsk,
      Russia. OBJECTIVE: To describe the incidence and management of hepatotoxicity
      during treatment of MDR-TB, and to assess risk factors associated with its
      development and impact on treatment outcomes. DESIGN: A retrospective case series
      performed among 608 patients. RESULTS: Hepatotoxicity, using American Thoracic
      Society (2006) definitions, was observed in 91/568 patients (16.5%). The median
      time to the first hepatotoxic event was 196 days post treatment commencement.
      Baseline factors associated  with hepatotoxicity included elevated alanine
      aminotransferase/aspartate aminotransferase/bilirubin (OR 53.9, 95%CI 6.30
      438.7), and renal insufficiency (OR 19.6, 95%CI 2.71-141.6). High treatment
      adherence (OR 3.25, 95%CI 2.07-5.09) and starting treatment in prison (OR 1.77, 
      95%CI 1.04-3.01) were associated with treatment success. Smoking (OR 0.44, 95%CI
      0.21-0.92) and bilateral cavitary disease (OR 0.51, 95%CI 0.34-0.77) were
      associated with worse outcomes. For alcohol users, developing hepatotoxicity was
      associated with better outcomes (OR  4.40, 95%CI 1.79-10.81) than not (OR 0.42,
      95%CI 0.25-0.68). One or more medications were permanently stopped in 10/91
      patients, but in no case was treatment entirely discontinued. CONCLUSION: MDR-TB
      treatment in the face of hepatotoxicity during therapy did not result in a 
      statistically significant increase in poor outcomes.

PMID- 22410437
TI  - Where do we go from here?

PMID- 22410438
TI  - Susceptibility of estrogen receptor rapid responses to xenoestrogens:
      Physiological outcomes.
AB  - 17beta-Estradiol (E2) binding induces rapid modification in the conformation of
      its cognate receptors (i.e., ERalpha and ERbeta). These allosteric changes allow
      the association of ERs with cell specific transcriptional cofactors, thus
      determining cellular contexts specific variations in gene expression. In
      addition, E2-ER complexes could also interact with membrane and cytosolic signal
      molecules triggering extra-nuclear signalling pathways. The synergy between these
      mechanisms is necessary for E2-induced pleiotropic actions in target tissues.
      Besides E2, the ER ligand binding domains can accommodate many other natural and
      synthetic ligands. Several of these compounds act as agonist or antagonist of ER
      transcriptional activity due to their ability to modify the interactions between
      ERs and transcriptional co-regulators. However, the ability of natural or manmade
      ER ligands to affect the extra-nuclear interactions of the ERs has been rarely
      evaluated. Here, the ability of two diet-derived flavonoids (i.e., naringenin and
      quercetin) and of the synthetic food-contaminant bisphenol A to modulate
      specifically ER extra-nuclear signalling pathways will be reported. All the
      tested compounds bind to both ER subtypes even if lesser than E2 activating
      divergent signal transduction pathways. In fact, in the presence of ERalpha, both
      naringenin and quercetin decouple ERalpha activities by specifically interfering
      with ERalpha membrane initiating signals. On the other hand, bisphenol A, but not
      flavonoids, maintains ERbeta at the membrane thus impairing the activation of the
      downstream kinases. As a whole, extra-nuclear ER signals are highly susceptible
      to different ligands that, by unbalancing E2-induced cell functions drive cells
      to different functional endpoints.

PMID- 22410439
TI  - Estrogen regulation of epithelial ion transport: Implications in health and
      disease.
AB  - Estrogen, 17beta-estradiol (E2), has been shown to modulate the activity of ion
      channels in a diverse range of epithelial tissues. The channel activation or
      inhibition responses to E2 are often rapid, occurring in seconds to minutes,
      independent of protein synthesis and gene transcription ('non-genomic' response).
      These rapid effects of E2 require activation of specific protein kinases or
      changes in intracellular calcium and pH which in turn modulate the conductance,
      open probability or number of channels in the plasmamembrane. Estrogen has also
      been shown to affect the expression of ion transporters over days ('genotropic'
      response) causing long-term sustained changes in transepithelial ion transport.
      It is now accepted that so called non-genomic responses are not stand-alone
      events and are necessary to prime the latent genomic response and even be
      critical for the full latent response to occur. In a number of epithelia the non
      genomic and genotropic responses to estrogen are sex-specific and variable in
      potency and sensitivity to E2 depending on the stage of the estrous cycle. Of
      increasing interest is the effect these rapid and latent actions of E2 on ion
      transporters have on the physiological functions of epithelia. For example,
      estrogen regulation of a class of voltage-gated K(+) channels (KCNQ1) can
      determine the rate of Cl(-) secretion in the intestine. In whole-body terms, the
      combined effects of estrogen on a variety of ion channels which control fluid and
      electrolyte transport in the kidney, intestine and lung may be necessary for
      endometrial expansion and implantation of the blastocyte.

PMID- 22410440
TI  - Significance of genomic rearrangements in epilepsy.

PMID- 22410441
TI  - Volume transmission-mediated encephalopathies: a possible new concept?
AB  - There is strong evidence that the composition of cerebrospinal fluid (CSF)
      influences brain development, neurogenesis, and behavior. The bidirectional
      exchange of CSF and interstitial fluid (ISF) across the ependymal and pia-glial
      membranes is required for these phenomena to occur. Because ISF surrounds the
      parenchymal compartment, neuroactive substances in the CSF and ISF can influence
      neuronal activity. Functionally important neuroactive substances are distributed
      to distant sites of the central nervous system by the convection and diffusion of
      CSF and ISF, a process known as volume transmission. It has recently been shown
      that pathologically altered CSF from patients with acute traumatic brain injury
      suppresses in vitro neuronal network activity (ivNNA) recorded by multielectrode
      arrays measuring synchronously bursting neural populations. Functionally relevant
      substances in pathologically altered CSF have been biochemically identified, and
      ivNNA has been partially recovered by pharmacologic intervention. It remains
      unclear whether the in vivo parenchymal compartment remains unaffected by
      pathologically altered CSF that significantly impairs ivNNA. We hypothesize that
      pathologic CSF alterations are not just passive indicators of brain diseases but
      that they actively and directly evoke functional disturbances in global brain
      activity through the distribution of neuroactive substances, for instance,
      secondary to focal neurologic disease. For this mechanism, we propose the new
      term volume transmission-mediated encephalopathies (VTE). Recording ivNNA in the
      presence of pure human CSF could help to identify and monitor functionally
      relevant CSF alterations that directly result in VTEs, and the collected data
      might point to therapeutic ways to antagonize these alterations.

PMID- 22410442
TI  - Effect of EPI-743 on the clinical course of the mitochondrial disease Leber
      hereditary optic neuropathy.
AB  - OBJECTIVE: To evaluate the safety and efficacy of a new therapeutic agent, EPI
      743, in Leber hereditary optic neuropathy (LHON) using standard clinical,
      anatomic, and functional visual outcome measures. DESIGN: Open-label clinical
      trial. SETTING: University medical center. Patients  Five patients with
      genetically confirmed LHON with acute loss of vision were consecutively enrolled
      and treated with the experimental therapeutic agent EPI-743 within 90 days of
      conversion. Intervention  During the course of the study, 5 consecutive patients
      received EPI-743, by mouth, 3 times daily (100-400 mg per dose). MAIN OUTCOME
      MEASURES: Treatment effect was assessed by serial measurements of anatomic and
      functional visual indices over 6 to 18 months, including Snellen visual acuity,
      retinal nerve fiber layer thickness measured by optical coherence tomography,
      Humphrey visual fields (mean decibels and area with 1-log unit depression), and
      color vision. Treatment effect in this clinical proof of principle study was
      assessed by comparison of the prospective open-label treatment group with
      historical controls. RESULTS: Of 5 subjects treated with EPI-743, 4 demonstrated
      arrest of disease progression and reversal of visual loss. Two patients exhibited
      a total recovery of visual acuity. No drug-related adverse events were recorded.
      CONCLUSIONS: In a small open-label trial, EPI-743 arrested disease progression
      and reversed vision loss in all but 1 of the 5 consecutively treated patients
      with LHON. Given the known natural history of acute and rapid progression of LHON
      resulting in chronic and persistent bilateral blindness, these data suggest that
      the previously described irreversible priming to retinal ganglion cell loss may
      be reversed.

PMID- 22410443
TI  - Long-term follow-up of acute partial transverse myelitis.
AB  - BACKGROUND: Acute partial transverse myelitis (APTM) may be the first clinical
      symptom of multiple sclerosis (MS) or may remain a monophasic event. OBJECTIVES:
      To evaluate the risk of conversion to MS and long-term disability, and to
      determine prognosis factors for disability. DESIGN: We identified patients with
      no previous history of neurological disease who experienced APTM between January
      1998 and December 2005 and were followed up at 3 university hospitals in France.
      Data on the patients' demographics and clinical states during follow-up, as well
      as data on cerebrospinal fluid (CSF) analysis, brain and spinal cord magnetic
      resonance imaging (MRI), and visual evoked potentials, were analyzed. SETTING:
      Neurology departments of 3 university hospitals in Lille, Strasbourg, and Rouen,
      France, respectively. PATIENTS: A total of 85 patients with no previous history
      of neurological disease who experienced APTM. RESULTS: The mean (SD) follow-up
      period was 104.8 (29.8) months. There were 57 women (67%) and 28 men (33%), with
      a mean (SD) age at onset of 36.7 (11.7) years. At the end of follow-up, 53
      patients (62%) were classified as having MS with a mean (SD) Expanded Disability
      Status Scale score of 2.6 (1.8), 1 patient (1%) was classified as having
      postinfectious myelitis, 1 (1%) as having neuromyelitis optica, 1 (1%) as having
      Sjogren syndrome, and 29 (34%) still had APTM of undetermined etiology.
      Oligoclonal bands in CSF were more frequent in patients with MS (92%) than in
      patients with APTM of undetermined etiology (38%). Brain MRI results were
      abnormal in 87% of patients with MS and 27% of patients with APTM of undetermined
      etiology; visual evoked potentials were abnormal in 43% of patients with MS and
      4% of patients with APTM of undetermined etiology. Oligoclonal bands in CSF (odds
      ratio, 15.76 [95% CI, 2.95-84.24]) and at least 1 MRI-detected brain lesion (odds
      ratio, 7.74 [95% CI, 2.42-24.74]) were independent predictive factors for
      conversion to MS. CONCLUSION: Our study confirms that abnormal brain MRI results
      and the presence of oligoclonal bands in CSF are 2 independent predictive factors
      for conversion to MS. No clinical, biological, or MRI factor at onset was
      predictive of long-term disability.

PMID- 22410444
TI  - Incidence of new-onset seizures in mild to moderate Alzheimer disease.
AB  - OBJECTIVE: To estimate the incidence rate and predictors of seizures in patients
      with mild to moderate Alzheimer disease (AD). DESIGN: Cohort study of patients
      with mild to moderate AD in clinical trials. Risk factors for potential seizures
      were evaluated by stratified descriptive statistics and univariable and
      multivariable Cox proportional hazards regressions. SETTING: Pooled patient-level
      data from 10 Alzheimer Disease Cooperative Study clinical trials in mild to
      moderate AD from 1995 to 2010. PATIENTS: Three thousand seventy-eight subjects
      randomized to the treatment or placebo arms of 10 AD clinical trials. Screening
      Mini-Mental State Examination scores ranged between 10 and 28. RESULTS: Eighteen
      seizures were reported in 3078 randomized subjects, with an incidence rate of 484
      per 100 000 person-years (95% CI, 287-764). Statistically significant independent
      risk factors for seizure were younger age (adjusted hazard ratio, 0.80; 95% CI,
      0.69-0.93 per every 5 years of age), greater cognitive impairment at baseline
      (adjusted hazard ratio, 2.79; 95% CI, 1.06-7.33 for Mini-Mental State Examination
      scores <18 compared with Mini-Mental State Examination scores >=18), and
      antipsychotic use at baseline (adjusted hazard ratio, 3.47; 95% CI, 1.33-9.08).
      CONCLUSIONS: Seizure rates in patients with mild to moderate AD in clinical
      trials are similar to rates observed in longer observational cohort studies, but
      they are greater than expected in the general elderly population. Younger age,
      greater degree of cognitive impairment, and history of antipsychotic use were
      independent risk factors for new-onset seizures in AD.

PMID- 22410445
TI  - Identification of Alzheimer disease risk genotype that predicts efficiency of
      SORL1 expression in the brain.
AB  - OBJECTIVE: To identify SORL1 risk genotypes that determine receptor protein
      expression in the human brain. DESIGN: DNA, RNA, and proteins were extracted from
      brain autopsies of Alzheimer disease cases and used for SORL1 genotyping, RNA
      profiling, and SORLA protein quantification, respectively. SETTING: Specimens
      were provided by the MRC London Brain Bank for Neurodegenerative Diseases and the
      Netherlands Brain Bank. SUBJECTS: Brain autopsy material (frontal cortex) from 88
      confirmed cases of sporadic Alzheimer disease. RESULTS: Our studies identified a
      SORL1 haplotype in the 3' gene region consisting of single-nucleotide
      polymorphisms rs1699102 and rs2070045 that is associated with poor receptor
      expression in the brain of patients with Alzheimer disease. These gene variations
      alter the SORL1 transcript sequence, resulting in a change from frequent to rare
      codon usage in the minor risk genotype. Studies in cultured cells confirm less
      efficient translation of the minor receptor transcripts into protein. CONCLUSION:
      Our findings suggest a functional mechanism that correlates SORL1 genotype with
      efficiency of receptor expression in the human brain.

PMID- 22410446
TI  - Prospective study of statin use and risk of Parkinson disease.
AB  - OBJECTIVE: To prospectively examine whether use of statins is associated with
      altered risk of Parkinson disease (PD). DESIGN, SETTING, AND PARTICIPANTS: A
      prospective study including 38 192 men and 90 874 women participating in 2
      ongoing US cohorts, the Health Professional Follow-up Study and the Nurses'
      Health Study, was conducted. Information on regular cholesterol-lowering drug use
      (>=2 times/wk) was collected in 1994 in both cohorts via questionnaire. Relative
      risks (RRs) and 95% CIs were computed using Cox proportional hazards models
      adjusting for age, smoking, caffeine intake, duration of hypercholesterolemia,
      and other covariates. MAIN OUTCOME MEASURE: Incident PD. RESULTS: During 12 years
      of follow-up (1994-2006), we documented 644 incident PD cases (338 women and 306
      men). The risk of PD was lower among current statin users (adjusted pooled RR =
      0.74; 95% CI, 0.54-1.00; P = .049) relative to nonusers. A significant
      association was observed in participants younger than 60 years at baseline
      (adjusted pooled RR = 0.31; 95% CI, 0.11-0.86; P = .02) but not among those who
      were older (adjusted pooled RR = 0.83; 95% CI, 0.60-1.14; P = .25) (P for
      interaction = .03). CONCLUSIONS: We found that regular use of statins was
      associated with a modest reduction in PD risk. The possibility that some statins
      may reduce PD risk deserves further consideration.

PMID- 22410447
TI  - Relationship between mitochondria and alpha-synuclein: a study of single
      substantia nigra neurons.
AB  - OBJECTIVE: To explore the relationship between alpha-synuclein pathology and
      mitochondrial respiratory chain protein levels within single substantia nigra
      neurons. DESIGN: We examined alpha-synuclein and mitochondrial protein expression
      in substantia nigra neurons of 8 patients with dementia with Lewy bodies, 5
      patients with Parkinson disease, and 8 control subjects. Protein expression was
      determined using immunocytochemistry followed by densometric analysis. PATIENTS:
      We examined single substantia nigra neurons from 5 patients with idiopathic
      Parkinson disease (mean age, 81.2 years), 8 patients with dementia with Lewy
      bodies (mean age, 75 years), and 8 neurologically and pathologically normal
      control subjects (mean age, 74.5 years). The control cases showed minimal Lewy
      body pathology and cell loss. Patients with dementia with Lewy bodies and
      idiopathic Parkinson disease fulfilled the clinical and neuropathologic criteria
      for these diseases. RESULTS: Our results showed that mitochondrial density is the
      same in nigral neurons with and without alpha-synuclein pathology. However, there
      are significantly higher levels of the respiratory chain subunits in neurons
      containing alpha-synuclein pathology. CONCLUSIONS: The finding of increased
      levels of respiratory chain complex subunits within neurons containing alpha
      synuclein does not support a direct association between mitochondrial respiratory
      chain dysfunction and the formation of alpha-synuclein pathology.

PMID- 22410448
TI  - Reduced uptake of FDOPA PET in end-stage liver disease with elevated manganese
      levels.
AB  - OBJECTIVE: To investigate whether manganese toxicity secondary to end-state liver
      disease is associated with nigrastriatal dysfunction as measured by 6
      [(18)F]fluoro-L-DOPA (FDOPA) positron emission tomographic (PET) imaging. DESIGN:
      Observational case report. SETTING: The Movement Disorder Center at Washington
      University, St Louis, Missouri. PATIENT: An individual with manganese toxicity
      secondary to end-stage liver disease. His FDOPA PET was compared with those of 10
      idiopathic Parkinson disease patients and 10 age- and sex-matched healthy
      controls. MAIN OUTCOME MEASURE: The average estimated net FDOPA uptake by Patlak
      graphical analysis for caudate, anterior putamen, and posterior putamen. RESULTS:
      The FDOPA uptake for the patient with secondary manganese toxicity was reduced
      across all regions by more than 2 SDs compared with healthy controls: caudate
      (reduced 24.7%), anterior putamen (28.0%), and posterior putamen (29.3%). The
      ratio of uptake between the caudate/posterior putamen was 0.99 and was different
      from that of idiopathic Parkinson disease patients, in whom the greatest
      reduction of FDOPA was in the posterior putamen (mean [SD] ratio, 1.65 [0.41]).
      CONCLUSIONS: Reduce striatal uptake of FDOPA uptake indicates dysfunction of the
      nigrostriatal pathways in manganese toxicity secondary to end-stage liver
      disease. The pattern of striatal involvement with equal reduction of FDOPA uptake
      in the caudate compared with posterior putamen appears different from those
      previously reported in individuals with occupational manganese toxicity and
      idiopathic Parkinson disease and may be specific to manganese toxicity secondary
      to end-stage liver disease.

PMID- 22410449
TI  - Partial trisomy 4q associated with young-onset dopa-responsive parkinsonism.
AB  - OBJECTIVE: To describe a patient who developed a young-onset, dopa-responsive
      parkinsonism linked to a de novo heterozygous interstitial duplication 4q.
      DESIGN: Case report. SETTING: Movement Disorder Outpatient Clinic at the
      University Hospital Centre, Liege, Belgium. PATIENT: A 31-year-old woman. MAIN
      OUTCOME MEASURES: Clinical, neuroimaging, and genetic data. RESULTS: The
      duplicated region contains 150 known genes, including the alpha-synuclein (SNCA)
      gene locus. Motor and 6-[(18)F]fluoro-L-dopa positron emission tomography
      features are similar to those previously reported in heterozygote SNCA
      duplication carriers. Altered expression of other genes contained in the
      duplicated region may contribute to clinical features that are uncommon in the
      phenotypic spectrum of SNCA multiplications such as delayed developmental
      psychomotor milestones during infancy and musculoskeletal abnormalities.
      CONCLUSION: This case report provides new insights on the genetic basis of
      parkinsonism.

PMID- 22410450
TI  - Primary progressive aphasia and transient global amnesia.
AB  - OBJECTIVE: To describe 3 patients with a history of transient global amnesia
      (TGA) who developed primary progressive aphasia (PPA). DESIGN: Case series.
      SETTING: Tertiary care center. PATIENTS: The study included 3 patients who
      presented to the neurology clinic with language complaints. MAIN OUTCOME MEASURE:
      Presence of recurrent TGA and PPA. RESULTS: Three patients with a history of TGA
      were subsequently diagnosed as having PPA. All patients had recurrent attacks of
      TGA. The diagnoses of PPA were supported by speech pathology evaluations,
      neuropsychometric testing results, and imaging findings. Positron emission
      tomography revealed left posterior frontal hypometabolism in 1 patient and
      predominantly left temporal parietal hypometabolism in 1 patient, while single
      photon emission computed tomography demonstrated decreased perfusion in the
      anterior left temporal and frontal lobes in the third patient. CONCLUSION: There
      may be a relationship between recurrent TGA and the development of PPA.

PMID- 22410452
TI  - Myofasciitis: imaging and pathology.

PMID- 22410451
TI  - Rapid reversal of wall-eyed bilateral internuclear ophthalmoplegia.

PMID- 22410453
TI  - Owl's eye in spinal magnetic resonance imaging.

PMID- 22410454
TI  - Giant aneurysm of the internal carotid artery.

PMID- 22410455
TI  - Ordering of Alzheimer disease biomarkers.

PMID- 22410457
TI  - Personalized management of patients with solid cancers:  moving from patient
      characteristics to tumor biology.
AB  - PURPOSE OF REVIEW: In recent years, there has been a paradigm shift in the
      diagnosis as well as the treatment of solid tumors. This review will detail some
      of the recent findings that led to better subtyping and treatment of cancers,
      some of which were historically refractory. RECENT FINDINGS: Advances in
      molecular biology have recently led to the rapid development of personalized
      cancer management. Molecular markers and gene signatures allow better risk
      definition and treatment prediction, thus, avoiding 'wasted toxicity'. Recent
      understandings in disease pathways are giving new hope to treatment of hard-to
      treat cancers such as melanoma, subtypes of nonsmall cell lung cancer and several
      orphan tumors. SUMMARY: This progress transposed from lab to bedside has made
      personalized cancer care a reality. In addition, this concept is being integrated
      into clinical trial designs with the enrolment of molecularly selected patients,
      hopefully leading to high rates of success.

PMID- 22410456
TI  - Combining immunological and androgen-directed approaches:  an emerging concept in
      prostate cancer immunotherapy.
AB  - PURPOSE OF REVIEW: The autologous antigen-presenting cell immunotherapy,
      sipuleucel-T, was the first and remains the only US Food and Drug Administration
      approved immunotherapy for prostate cancer. In this article, we will summarize
      recent clinical data on several additional immune-directed strategies, some of
      which have now entered phase 3 trials. RECENT FINDINGS: Multiple studies are now
      testing sipuleucel-T in different disease settings and/or in combination with
      conventional and novel hormonal therapies. In addition, a poxviral-based vaccine
      has shown promise in early-phase clinical studies and has now entered phase 3
      testing in men with metastatic prostate cancer. Next, a DNA vaccine has been
      evaluated in men with biochemically recurrent prostate cancer and has shown early
      signs of clinical efficacy. Finally, several studies are evaluating the role of
      immune checkpoint blockade using ipilimumab in pivotal phase 3 trials in prostate
      cancer patients with advanced disease, as well as in earlier phase studies in
      combination with androgen ablation. SUMMARY: The abundance of new treatment
      options for men with advanced prostate cancer will challenge the role of
      immunotherapy in these patients. Future progress may rely on optimal combination
      and sequencing of various immunotherapies with androgen-directed approaches as
      well as with other standard prostate cancer therapies, an effort which is now
      just beginning.

PMID- 22410458
TI  - Vascular disrupting agents:  a delicate balance between efficacy and side
      effects.
AB  - PURPOSE OF REVIEW: Targeting the tumor vasculature is an attractive approach for
      cancer therapy. Vascular disrupting agents (VDAs) are compounds that directly
      target tumor blood vessels and create central tumor necrosis. The current review
      aims to summarize the clinical development (i.e. safety and efficacy) of this
      class of compounds. RECENT FINDINGS: VDAs have demonstrated signs of clinical
      activity in different tumor types [e.g. anaplastic thyroid carcinoma (ATC),
      nonsmall cell lung carcinoma (NSCLC), ovarian cancer, sarcoma]. However, the lack
      of predictive biomarkers to identify patients with a high probability of response
      to VDAs, places this class of compounds at a high risk of failure. This has
      recently been exemplified by several negative phase II/III trials in NSCLC, ATC,
      and castration-refractory metastatic prostate cancer. SUMMARY: VDAs represent a
      unique class of anticancer compounds. Their clinical development is hampered by
      cardiovascular, neurological toxicities as single agent and by hematological
      toxicity in combination with chemotherapy. Molecular predictors of their efficacy
      are crucial for further development. As single agent, only few objective
      responses have been observed in a variety of solid tumors. However, VDAs have
      failed to demonstrate a survival advantage in several phase II/III trials
      especially in combination with chemotherapy.

PMID- 22410459
TI  - WITHDRAWN:New PET imaging agents in the management of solid cancers.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 22410460
TI  - Molecular imaging training for nuclear medicine residents.

PMID- 22410461
TI  - Potential of PET to predict the response to trastuzumab treatment in an ErbB2
      positive human xenograft tumor model.
AB  - Currently, an alteration in the gross volume of a tumor is used to assess its
      response to trastuzumab; however, this approach provides only a late indication
      of response. Tissue-sample ex vivo assays are potentially valuable, but their
      procurement through biopsies is invasive and might be biased by tumor
      heterogeneity. We studied the feasibility of using PET to quantify changes in
      ErbB2 (HER2/neu) expression and to predict the response to trastuzumab in BT474
      breast cancer xenografts with N-[2-(4-(18)F-fluorobenzamido)ethyl]maleimide
      ((18)F-FBEM)-HER(2:342) Affibody. METHODS: Mice bearing BT474 tumors were given
      trastuzumab (50 mg/kg loading dose, 25 mg/kg maintenance dose, administered
      intraperitoneally twice a week) or saline (control) for a total of 5 doses. Tumor
      size was monitored twice a week. Animals were scanned before the treatment, at 48
      h, and 2 wk after the beginning of therapy. After the final scan, PET results
      were correlated with tumor response and immunohistochemical assessment of ErbB2
      level, as well as with vasculature in the treated tumors. RESULTS: Analysis of
      PET images indicated that tracer uptake was significantly reduced after 1 dose of
      trastuzumab, compared with baseline, suggesting applicability as an early
      indicator of changes in ErbB2 expression. After 5 doses of trastuzumab, the
      overall decrease in (18)F-FBEM-HER(2:342) Affibody uptake also correlated with
      tumor response and downregulation of ErbB2 expression by immunohistochemical
      assessment. However, individual animals had different responses. There was a
      correlation between bigger PET changes and a higher vessel count in the tumors,
      suggesting that an increased number of vessels could lead to better trastuzumab
      delivery. We confirmed that the difference in average vessel count in the tumors
      was not related to the size of the tumors and therefore was not due to the
      selection of more vascular tumors. This finding is consistent with previous
      findings demonstrating that the number of vessels in a tumor could be a useful
      prognostic marker for treatment response. CONCLUSION: Our data suggest that
      Affibody-based PET can noninvasively provide specific information on changes in
      receptor expression and could be a valuable strategy for predicting tumor
      response to trastuzumab.

PMID- 22410462
TI  - Radiodosimetric estimates for radioembolic therapy of liver tumors: challenges
      and opportunities.

PMID- 22410463
TI  - Gambogenic acid induces G1 arrest via GSK3beta-dependent cyclin D1 degradation
      and triggers autophagy in lung cancer cells.
AB  - Cyclin D1, an oncogenic G1 cyclin which can be induced by environmental
      carcinogens and whose over-expression may cause dysplasia and carcinoma, has been
      shown to be a target for cancer chemoprevention and therapy. In this study, we
      investigated the effects and underlying mechanisms of action of a polyprenylated
      xanthone, gambogenic acid (GEA) on gefitinib-sensitive and -resistant lung cancer
      cells. We found that GEA inhibited proliferation, caused G1 arrest and repressed
      colony-forming activity of lung cancer cells. GEA induced degradation of cyclin
      D1 via the proteasome pathway, and triggered dephosphorylation of GSK3beta which
      was required for cyclin D1 turnover, because GSK3beta inactivation by its
      inhibitor or specific siRNA markedly attenuated GEA-caused cyclin D1 catabolism.
      GEA induced autophagy of lung cancer cells, possibly due to activation of
      GSK3beta and inactivation of AKT/mTOR signal pathway. These results indicate that
      GEA is a cyclin D1 inhibitor and a GSK3beta activator which may have
      chemopreventive and therapeutic potential for lung cancer.

PMID- 22410464
TI  - Targeting survivin in cancer.
AB  - With almost 4000 citations in Medline in a little over 10 years, survivin has
      certainly kept scores of investigators busy worldwide. Tangible progress has been
      made in revealing the multiple functions of survivin, uncovering their wirings as
      integrated cellular networks, and mapping their exploitation in virtually every
      human tumor, in vivo. Considering the normally long and excruciating timeline of
      oncology drug discovery, it is clearly a resounding success that a better
      understanding of survivin biology has led to several clinical trials of survivin
      based therapeutics in cancer patients. However, the portfolio of survivin
      antagonists available in the clinic remains small, pressing the need for a less
      rigid drug development approach to fully unlock the potential of this unique,
      albeit unconventional oncology drug target.

PMID- 22410465
TI  - Differential expression of peach ERF transcriptional activators in response to
      signaling molecules and inoculation with Xanthomonas campestris pv. pruni.
AB  - Ethylene response factors (ERFs) are a large family of transcription factors
      (TFs) that have diverse functions in plant development and immunity. However,
      very little is known about the molecular regulation of these TFs in stone fruits
      during disease incidence. In the present study, we describe the identification of
      five peach ERFs (Pp-ERFs), aiming to elucidate their potential roles in defense
      against Xanthomonas campestris pv. pruni (Xcp), the causal agent of bacterial
      spot disease. The phylogenetic analysis along with sequence comparisons indicated
      that all Pp-ERFs are transcriptional activators belonging to groups IX and IIV
      ERFs. The transactivation capacity of these proteins was verified in vivo where
      they all induced the expression of the GUS reporter gene and in a GCC-dependent
      manner. The nuclear localization was also confirmed for two of these proteins, Pp
      ERF2.b and Pp-ERF2.c, after their transient expression in onion epidermal cells.
      The induction kinetics of Pp-ERFs after inoculation with Xcp was determined by
      qRT-PCR. Except for Pp-ERF2.b, transcript levels of Pp-ERFs increased strongly
      and rapidly in the resistant 'Venture' compared to the susceptible 'BabyGold 5'
      cultivar after infection with Xcp. In contrast, the expression of Pp-ERF2.b was
      several-fold higher in the susceptible cultivar after bacterial infection. The
      expression of Pp-ERFs was also monitored after treating with signaling compounds;
      salicylic acid (SA) (1 mM), ethephon (1 mM) and methyl jasmonate (MeJA) (50 MUM).
      Although the results generally emphasize the role of ethylene/jasmonic acid
      (ET/JA) signaling pathways in regulating the expression of Pp-ERFs, there was a
      coordination of the timing of ET/JA responses, suggesting compensatory rather
      than synergistic interactions between these pathways during defense against Xcp.

PMID- 22410466
TI  - Abscisic acid substantially inhibits senescence of cucumber plants (Cucumis
      sativus) grown under low nitrogen conditions.
AB  - Low nitrogen (N) availability such as that found in both dry land and tropical
      regions limits plant growth and development. The relationship between the level
      of abscisic acid (ABA) in a plant and its growth under low-N conditions was
      investigated. The level of ABA in cucumber (Cucumis sativus) plants under low-N
      conditions was significantly higher at 10 and 20 d after transplantation compared
      with that under sufficient-N conditions. Chlorophyll was preserved in the aerial
      parts of cucumber plants grown under low-N conditions in the presence of ABA,
      while there was no significant difference between control plants and ABA-applied
      plants under sufficient-N conditions. ABA suppressed the reduction of chlorophyll
      biosynthesis under low-N conditions but not under sufficient-N conditions. On the
      other hand, ABA decreased the expression of the chlorophyll degradation gene in
      older cucumber plants grown under both conditions. In addition, transcript and
      protein levels of a gene encoding a chlorophyll a/b binding protein were
      positively correlated with ABA concentration under low-N conditions. The
      chloroplasts in control plants were round, and the stack of thylakoid membranes
      was reduced compared with that of plants treated with ABA 10(-5) M. These results
      strongly suggest that ABA is accumulated in cucumber plants grown under low-N
      conditions and that accumulated ABA promotes chlorophyll biosynthesis and
      inhibits its degradation in those plants.

PMID- 22410467
TI  - Comparison of endogenous cytokinins and cytokinin oxidase/dehydrogenase activity
      in germinating and thermoinhibited Tagetes minuta achenes.
AB  - Tagetes minuta L. achenes are thermoinhibited at temperatures above 35 degrees C
      and have accelerated radicle emergence (germination) when subsequently
      transferred to an optimal temperature (25 degrees C). Endogenous cytokinins and
      cytokinin oxidase/dehydrogenase (CKX) activity were compared in normally
      germinating (25 degrees C) and thermoinhibited (72h at 36 degrees C then
      transferred to 25 degrees C) T. minuta achenes. Following imbibition, endogenous
      cytokinin concentrations changed in normally germinating T. minuta achenes, with
      a gradual decrease in dihydrozeatin-type (DHZ) cytokinins, a large increase in
      cis-zeatin-type (cZ) cytokinins, a smaller increase in N6-(2-isopentenyl)adenine
      type (iP) cytokinins and a peak of trans-zeatin-type (tZ) cytokinins at 13 h.
      These changes in the isoprenoid cytokinin profile were similar in the
      thermoinhibited achenes imbibed at 36 degrees C, despite the thermal block
      preventing radicle emergence. The exception was the iP-type cytokinins that only
      increased when transferred to 25 degrees C. Profiles of the physiologically
      active free bases showed an increase in tZ prior to radical emergence in both
      normally germinating (13 h) and thermoinhibited achenes. A large transient peak
      in aromatic cytokinins [N6-benzyladenine-type (BA)] occurred during early
      seedling establishment in normally germinating achenes (40 h) while a transient
      maximum in BA-type cytokinins was found prior to radicle emergence in the
      thermoinhibited achenes (24 h). The CKX activity was enhanced in normally
      germinating achenes as the cytokinin concentration increased following
      imbibition. In thermoinhibited achenes, an elevated temperature negatively
      affected the CKX activity that only increased when the achenes were transferred
      to 25 degrees C, corresponding to an increase in iP-type cytokinins. However, the
      favored cytokinin deactivation pathway in T. minuta appears to be 9
      glycosylation, as 9-glucosides accounted for over 50% of the total cytokinin pool
      in both normal and thermoinhibited achenes.

PMID- 22410468
TI  - Chronic obstructive pulmonary disease and metabolic syndrome: a nationwide survey
      in Korea.
AB  - SETTING: Systemic inflammation has been suggested to be involved in the
      pathogenesis of chronic obstructive pulmonary disease (COPD) and metabolic
      syndrome. However, the association between these two conditions is not fully
      understood. OBJECTIVE: To evaluate the relationship between COPD and metabolic
      syndrome. DESIGN: Among subjects aged >=40 years from the 2001 Korean National
      Health and Nutrition Examination Survey, 1215 subjects with two or more
      acceptable spirometry measurements and complete anthropometric/laboratory
      examinations were analysed. RESULTS: A total of 133 subjects (11%, 100 men and 33
      women) were newly diagnosed with COPD (forced expiratory volume in 1
      second/forced vital capacity <= 70%). The prevalence of metabolic syndrome, based
      on the National Cholesterol Education Program Adult Treatment Panel III, was
      significantly higher in COPD subjects compared with non-COPD subjects in both
      sexes (33.0% vs. 22.2% in men and 48.5% vs. 29.6% in women). In men, the risk of
      COPD was higher in subjects with metabolic syndrome than in those without (OR
      2.03, 95%CI 1.08-3.80), after adjusting for potential confounders. There was a
      borderline significant association between COPD and abdominal obesity among the
      individual component of metabolic syndrome (OR 1.95, 95%CI 0.93-4.11).
      CONCLUSION: In the Republic of Korea, metabolic syndrome was associated with COPD
      in men.

PMID- 22410469
TI  - Influence of a prolonged lateral position on induction of spinal anesthesia for
      cesarean delivery: a randomized controlled trial.
AB  - BACKGROUND: Maternal hypotension occurs commonly during cesarean delivery under
      spinal anesthesia. We evaluated whether hypotension due to aortocaval compression
      could be prevented by maintaining a lateral position after an intrathecal
      injection. METHODS: Eighty-six women undergoing elective cesarean delivery were
      enrolled. Spinal anesthesia was conducted in the right lateral position using 8
      mg of hyperbaric bupivacaine and 15 ug of fentanyl. Patients were randomly
      assigned to maintain the right lateral position for 6 min before assuming the
      wedged supine position (group L), or to assume the wedged supine position
      immediately after the spinal injection (group S). Hypotension was defined as a
      decrease in mean arterial pressure to <80% of baseline. Ephedrine was given if
      blood pressure decreased to <70% of baseline. The incidence of hypotension and
      nausea, ephedrine requirement, maximal block height, and neonatal outcomes were
      evaluated. RESULTS: No significant between-group differences were observed in the
      lowest blood pressure, total ephedrine dose, or incidence of hypotension or
      nausea. Onset of hypotension was delayed (6 +/- 2 vs. 10 +/- 3 min, P<0.001), and
      the sensory block level was more cephalad in group L than in group S (T2 [C8-T5]
      vs. T4 [T1-T6], P=0.001). Apgar scores did not differ between the groups.
      CONCLUSION: During spinal anesthesia for elective cesarean delivery, maintaining
      the lateral position for 6 min after an intrathecal injection of hyperbaric
      bupivacaine resulted in a more gradual and higher cephalad sensory block, without
      an increase in the incidence of maternal hypotension.

PMID- 22410470
TI  - Can we study Saturn's rings through binoculars?

PMID- 22410471
TI  - Two Japanese patients with Leigh syndrome caused by novel SURF1 mutations.
AB  - We report two patients with Leigh syndrome that showed a combination of facial
      dysmorphism and MRI imaging indicating an SURF1 deficiency, which was confirmed
      by sequence analysis. Case 1 is a 3-year-old girl with failure to thrive and
      developmental delay. She presented with tachypnea at rest and displayed facial
      dysmorphism including frontal bossing, lateral displacement of inner canthi,
      esotropia, maxillary hypoplasia, slightly upturned nostril, and hypertrichosis
      dominant on the forehead and extremities. Case 2 is an 8-year-old boy with
      respiratory failure. He had been diagnosed as selective complex IV deficiency.
      Case 2 displayed facial dysmorphism and hypertrichosis. Since both patients
      displayed characteristic facial dysmorphism and MRI findings, we sequenced the
      SURF1 gene and identified two heterozygous mutations; c.49+1 G>T and c.752_753del
      in Case 1, and homozygous c.743 C>A in Case 2. For patients with Leigh syndrome
      showing these facial dysmorphism and hypertrichosis, sequence analysis of the
      SURF1 gene may be useful.

PMID- 22410472
TI  - Reversible leukoencephalopathy with stroke-like presentation in a patient with 5
      dihydropyrimidine dehydrogenase deficiency treated with continuous 5-fluorouracil
      infusion.

PMID- 22410473
TI  - Ewing's sarcoma of the small intestine misdiagnosed as a voluminous pedunculated
      uterine leiomyoma.

PMID- 22410474
TI  - Unilateral deep brain stimulation of the pedunculopontine tegmental nucleus
      improves oromotor movements in Parkinson's disease.
AB  - BACKGROUND: Jaw movements are severely affected in Parkinson's disease. Deep
      brain stimulation (DBS) of basal ganglia targets is known to ameliorate oromotor
      control. In this study, we examined the effects of DBS of the pedunculopontine
      tegmental nucleus (PPTg) on jaw movements in selected parkinsonian patients.
      METHODS: The effects of low-frequency (25 Hz) stimulation of the PPTg on jaw
      movements were investigated through electrognathographic analysis in parkinsonian
      patients who were selected for PPTg stimulation. Changes in jaw velocity and
      amplitude during voluntary opening and closing movements of the mouth, as well as
      the maximum frequency of self-paced sequences of opening and closing cycles, were
      analyzed. RESULTS: Low-frequency stimulation of the PPTg in the OFF-drugs
      condition significantly improved the opening and closing velocities, vertical
      amplitude and rhythm of voluntary movements. In some instances, movement
      parameters during stimulation were within the range of those recorded in healthy
      controls. DISCUSSION: This is the first study investigating the impact of PPTg
      DBS on oromotor control in parkinsonian patients. The results show that jaw
      movements may be restored under stimulation and suggest that the pedunculopontine
      nucleus may play a key role in controlling oromotor activity.

PMID- 22410475
TI  - Individual effects of varying stimulation intensity and response criteria on area
      of activation for different muscles in humans. A study using navigated
      transcranial magnetic stimulation.
AB  - BACKGROUND: When using transcranial magnetic stimulation, a stimulation intensity
      defined as a certain level above the threshold for activation of a hand muscle is
      commonly used, disregarding the fact that the areas of activation for different
      muscles may have varying response characteristics intra- and interindividually.
      OBJECTIVE: To study the response characteristics of different muscles and compare
      them within and between individuals. Also to investigate the effect of varying
      stimulation intensity (defined in two different ways) and amplitude criterion for
      response, on the sizes of the activation areas for different muscles. METHODS: A
      system of transcranial magnetic stimulation with navigation capacity where the
      stimulation intensity can be defined in terms of the electric field strength in
      the tissue was used. Four different muscles were investigated in healthy adults.
      The threshold for activation at rest (RMT) of the different muscles and their
      respective areas of activation were quantified using three different stimulus
      intensities (100, 110 and 120% RMT) and two criteria for response amplitude (20
      and 50 MUV). RESULTS: Responses could readily be determined using 20 MUV as
      response limit. The RMTs for different muscles varied within and between
      individuals. The degree to which the area depended on stimulation intensity
      differed between muscles intra- and interindividually. All results were
      statistically significant (P < 0.05 or less). CONCLUSIONS: The response
      characteristics vary between muscles within an individual and between individuals
      for a certain muscle. Thus, for optimal accuracy when delineating the activation
      area, the investigation should be adapted to each particular muscle.

PMID- 22410476
TI  - Modulation of verbal fluency networks by transcranial direct current stimulation
      (tDCS) in Parkinson's disease.
AB  - BACKGROUND: Verbal fluency relies on the coordinated activity between left
      frontal and temporal areas. Patients with Parkinson's disease (PD) present
      phonemic and semantic fluency deficits. Recent studies suggest that transcranial
      direct current stimulation (tDCS) enhances adaptative patterns of brain activity
      between functionally connected areas. OBJECTIVE: The aim of this study was to
      assess the differences in the effects induced by tDCS applied to frontal and
      temporo-parietal areas on phonemic and semantic fluency functional networks in
      patients with PD. METHOD: Sixteen patients were randomized to receive tDCS to
      left dorsolateral prefrontal cortex (DLPFC) and left temporo-parietal cortex
      (TPC) in a counterbalanced order. Immediately following stimulation, patients
      underwent a verbal fluency paradigm inside a fMRI scanner. Changes induced by
      tDCS in activation and deactivation task-related pattern networks were studied
      using free-model independent component analyses (ICA). RESULTS: Functional
      connectivity in verbal fluency and deactivation task-related networks was
      significantly more enhanced by tDCS to DLPFC than to TPC. In addition, DLPFC tDCS
      increased performance on the phonemic fluency task, after adjusting for baseline
      phonemic performance. CONCLUSIONS: These findings provide evidence that tDCS to
      specific brain regions induces changes in large scale functional networks that
      underlay behavioural effects, and suggest that tDCS might be useful to enhance
      phonemic fluency in PD.

PMID- 22410477
TI  - Neurophysiological predictors of non-response to rTMS in depression.
AB  - BACKGROUND: The application of rTMS in Depression has been very well investigated
      over the last few years. However, little is known about predictors of non
      response associated with rTMS treatment. OBJECTIVE: This study examined
      neurophysiological parameters (EEG and ERP) in 90 depressed patients treated with
      rTMS and psychotherapy and sought to identify predictors of non-response.
      METHODS: This study is a multi-site open-label study assessing pre-treatment EEG
      and ERP measures associated with non-response to rTMS treatment. RESULTS: Non
      responders were characterized by 1) Increased fronto-central theta EEG power, 2)
      a slower anterior individual alpha peak frequency, 3) a larger P300 amplitude,
      and 4) decreased pre-frontal delta and beta cordance. A discriminant analysis
      yielded a significant model, and subsequent ROC curve demonstrated an area under
      the curve of 0.814. CONCLUSIONS: Several EEG variables demonstrated clear
      differences between R and NR such as the anterior iAPF, fronto-central Theta and
      pre-frontal cordance in the Delta and Beta band (representative of increased
      relative pre-frontal perfusion). The increased P300 amplitude as a predictor for
      non-response requires further study, since this was the opposite as hypothesized
      and there were no correlations of this measure with clinical improvement for the
      whole sample. Combining these biomarkers in a discriminant analysis resulted in a
      reliable identification of non-responders with low false positive rates. Future
      studies should prospectively replicate these findings and also further
      investigate appropriate treatments for the sub-groups of non-responders
      identified in this study, given that most of these biomarkers have also been
      found in antidepressant medication studies.

PMID- 22410478
TI  - H(2)(15)O PET responses to deep brain stimulation.

PMID- 22410479
TI  - Reply to letter to the editor "H(2)(15)O PET responses to deep brain
      stimulation".

PMID- 22410480
TI  - MRI-targeted repetitive transcranial magnetic stimulation of Heschl's gyrus for
      refractory auditory hallucinations.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has shown promise
      as a treatment for refractory auditory hallucinations (AH) in Schizophrenia. Most
      previous studies have examined the effect of low frequency, left-sided
      stimulation (LFL) (1 Hz) to the temporoparietal cortex (TPC). Priming stimulation
      (6 Hz) prior to LFL stimulation (hereby simply referred to as priming) has been
      shown to enhance the neurophysiological effects of LFL rTMS alone and, as such,
      may lead to greater attenuation of AH. OBJECTIVE: Therefore, this study evaluated
      the efficacy of priming rTMS and LFL rTMS compared to sham rTMS using MRI
      targeting of Heschl's gyrus (HG) within the TPC of subjects with SCZ experiencing
      refractory auditory hallucinations (AH). METHODS: Subjects between the ages of 18
      and 65 were recruited from a tertiary care university hospital. Fifty-four
      subjects with medication resistant AH were randomized to receive LFL, priming, or
      sham rTMS for 20 treatments. The primary outcome was reduction of hallucinatory
      symptoms as indexed by response rates on the Psychotic Symptoms Rating Scale
      (PSYRATS). RESULTS: The response rates did not differ among the three treatment
      groups using an intention to treat analysis. The response rates did not differ in
      any of the secondary outcome measures. The treatment was well tolerated with
      minimal adverse effects including no changes in cognition during the study.
      CONCLUSION: These findings suggest that neither priming nor LFL rTMS of Heschl's
      gyrus are effective at ameliorating refractory AH in schizophrenia.
      ClinicalTrials.gov Identifier: NCT01386918.

PMID- 22410481
TI  - Ultrasensitive detection of adrenocorticotropin hormone (ACTH) using disposable
      phenylboronic-modified electrochemical immunosensors.
AB  - This work reports for the first time an electrochemical immunosensor for the
      determination of adrenocorticotropin hormone (ACTH). The immunoelectrode design
      involves the use of amino phenylboronic acid for the oriented immobilization of
      anti-ACTH antibodies onto screen-printed carbon modified electrode surfaces. A
      competitive immunoassay between the antigen and the biotinylated hormone for the
      binding sites of the immobilized antibody was performed. The electroanalytical
      response was generated by using alkaline phosphatase-labelled streptavidin and 1
      naphtyl phosphate as the enzyme substrate. The electrochemical oxidation of the
      enzyme reaction product, 1-naphtol, measured by differential pulse voltammetry
      was employed to monitor the affinity reaction. Under the optimized working
      conditions, an extremely low detection limit of 18 pg/L was obtained. Cross
      reactivity was evaluated against other hormones (cortisol, estradiol,
      testosterone, progesterone, hGH and prolactin) and the obtained results
      demonstrated an excellent selectivity. The developed immunosensor was applied to
      a human serum sample containing a certified amount of ACTH with good results.

PMID- 22410482
TI  - Bioactivity of horseradish peroxidase entrapped in silica nanospheres.
AB  - Interest in the fabrication of micro/nanoreactors for evaluation of the function
      of biomolecules in biological processes, enzymatic reaction kinetics occurring
      inside the nanospace is rapidly increasing. With a simple reverse-micelle
      microemulsion method, horseradish peroxidase (HRP), a model biomolecule, was
      herein skillfully confined in silica nanoshells (HRP@SiO(2)) and its
      biocatalytical behaviors were investigated in detail. Spectroscopic measurements
      showed that the entrapped HRP molecules retained their native structure and had
      high enzymatic activity toward 3,3',5,5'-tetramethylbenzidine (TMB) with
      Michaelis constant (K(m)) of 3.02 * 10(-5) mol L(-1). The entrapped HRP displayed
      a good direct electron transfer behavior and sensitive electrocatalytic response
      toward the reduction of H(2)O(2), which could be enhanced using thionine and o
      phenylenediamine (o-PD) as electron mediators. When using thionine as mediator,
      the mass transport between the substrates in electrolyte and HRP confined in
      silica nanospheres through the mesoporous tunnels was slower than that of o-PD,
      which slowed down the electron transfer between heme in HRP in the confined
      nanospace and the electrode, and resulted in low sensitivity to H(2)O(2) with
      thionine as mediator when compared to o-PD.

PMID- 22410483
TI  - A study of electrochemical biosensor for analysis of three-dimensional (3D) cell
      culture.
AB  - Cell culture has a fundamental role not only in regenerative medicine but also in
      biotechnology, pharmacology, impacting both drug discovery and manufacturing.
      Although cell culture has been generally developed for only two-dimensional (2D)
      culture systems, three-dimensional (3D) culture is being spotlighted as the means
      to mimic in vivo cellular conditions. In this study, a method for cytotoxicity
      assay using an electrochemical biosensor applying 3D cell culture is presented.
      In order to strengthen the advantage of a 3D cell culture, the experimental
      condition of gelation between several types of sol-gels (alginate, collagen,
      matrigel) and cancer cells can be optimized to make a 3D cell structure on the
      electrode, which will show the reproducibility of electrical measurement for long
      term monitoring. Moreover, cytotoxicity test results applying this method showed
      IC(50) value of A549 lung cancer cells to erlotinib. Thus, this study evaluates
      the feasibility of application of the electrochemical biosensor for 3D cell
      culture to cytotoxicity assay for investigation of 3D cell response to drug
      compounds.

PMID- 22410484
TI  - Real-time analysis of the carbohydrates on cell surfaces using a QCM biosensor: a
      lectin-based approach.
AB  - A novel approach to the study of molecular interactions on the surface of
      mammalian cells using a QCM biosensor was developed. For this study, an
      epidermoid carcinoma cell line (A-431) and a breast adenocarcinoma cell line (MDA
      MB-468) were immobilized onto polystyrene-coated quartz crystals. The binding and
      dissociation between the lectin Con A and the cells as well as the inhibition of
      the binding by monosaccharides were monitored in real time and provided an
      insight into the complex avidic recognition of cell glycoconjugates. The real
      time lectin screening of a range of lectins, including Con A, DBA, PNA and UEA-I,
      enabled the accurate study of the glycosylation changes between cells, such as
      changes associated with cancer progression and development. Furthermore, the
      kinetic parameters of the interaction of Con A with MDA-MB-468 cells were
      studied. This application provides investigators in the field of glycobiology
      with a novel tool to study cell surface glycosylation and may also have impacts
      on drug discovery.

PMID- 22410485
TI  - Bilirubin oxidase from Bacillus pumilus: a promising enzyme for the elaboration
      of efficient cathodes in biofuel cells.
AB  - A CotA multicopper oxidase (MCO) from Bacillus pumilus, previously identified as
      a laccase, has been studied and characterized as a new bacterial bilirubin
      oxidase (BOD). The 59 kDa protein containing four coppers, was successfully over
      expressed in Escherichia coli and purified to homogeneity in one step. This 509
      amino-acid enzyme, having 67% and 26% sequence identity with CotA from Bacillus
      subtilis and BOD from Myrothecium verrucaria, respectively, shows higher turnover
      activity towards bilirubin compared to other bacterial MCOs. The current density
      for O(2) reduction, when immobilized in a redox hydrogel, is only 12% smaller
      than the current obtained with Trachyderma tsunodae BOD. Under continuous
      electrocatalysis, an electrode modified with the new BOD is more stable, and has
      a higher tolerance towards NaCl, than a T. tsunodae BOD modified electrode. This
      makes BOD from B. pumilus an attractive new candidate for application in biofuel
      cells (BFCs) and biosensors.

PMID- 22410486
TI  - Electrocatalytic oxidation and voltammetric determination of levodopa in the
      presence of carbidopa at the surface of a nanostructure based electrochemical
      sensor.
AB  - In the present paper, the use of a carbon paste electrode modified by meso
      tetrakis(3-methylphenyl) cobalt porphyrin (CP) and TiO(2) nanoparticles for the
      determination of levodopa (LD) and carbidopa (CD) was described. Initially,
      cyclic voltammetry was used to investigate the redox properties of this modified
      electrode at various scan rates. Next, the mediated oxidation of LD at the
      modified electrode was described. At the optimum pH of 7.0, the oxidation of LD
      occurs at a potential about 150 mV less positive than that of an unmodified
      carbon paste electrode. Based on differential pulse voltammetry (DPV), the
      oxidation of LD exhibited a dynamic range between 0.1 and 100.0 MUM and a
      detection limit (3sigma) of 69 +/- 2 nM. DPV was used for simultaneous
      determination of LD and CD at the modified electrode, and quantitation of LD and
      CD in some real samples (such as tablets of Parkin-C Fort and Madopar, water,
      urine, and human blood serum) by the standard addition method.

PMID- 22410487
TI  - An integrated microfluidic system for rapid screening of alpha-fetoprotein
      specific aptamers.
AB  - The systematic evolution of ligands by exponential enrichment (SELEX) is a
      screening technique that involves the progressive selection of highly specific
      ligands via repeated rounds of partition and amplification from a large random
      pool of nucleic acid sequences. The products of this selection process are called
      aptamers and are either short single-stranded deoxyribonucleic acid (ssDNA) or
      ribonucleic acid (RNA) molecules with a high binding affinity to a large variety
      of target analytes. However, SELEX is a lengthy, labor-intensive, iterative
      process requiring multiple rounds of extraction and polymerase chain reaction
      (PCR) amplification. In order to address these problems, this study presents a
      new integrated microfluidic system consisting of a magnetic bead-based
      microfluidic SELEX chip and a competitive assay chip to automate the aptamer
      screening process. More importantly, the selected ssDNA sequences were confirmed
      to have a high affinity and specificity to the target molecules, using the
      developed competitive assay chip. With this approach, an aptamer specific to
      alpha-fetoprotein (AFP), which is a biomarker for liver cancers, has been
      successfully selected. The screened aptamer was used as a recognition molecule
      for AFP and has a linear detection range from 12.5 to 800 ng/mL, which was
      suitable for rapid clinical applications.

PMID- 22410488
TI  - A nano-sized Au electrode fabricated using lithographic technology for
      electrochemical detection of dopamine.
AB  - One big challenge of fabricating nanosensors for spatially resolved
      electrochemical detection of neurochemicals, such as dopamine (DA), is the
      difficulty to assembly nanometer-scale patternable and integrated sensors. In
      this work we develop a novel approach to precisely manufacture nano-Au-electrode
      (NAE) using lithographic fabrication technique, and characterize the NAE for DA
      detection. A negative photoresist, SU-8, is used as a substrate and protection
      layer for the 127-nm Au active sensing layer. The cross surface morphology and
      thickness of the Au layer are imaged by scanning electron microscopy and an
      interference microscopy. This NAE could be precisely controlled, repeatedly
      fabricated and conveniently renewed for several times. The electrochemical
      sensitivity and selectivity of the NAE towards DA detection are significantly
      higher than those of a standard Au thin-film electrode. This work demonstrates
      that the NAE could be used as an attractive means for electrochemically sensing
      and recording DA.

PMID- 22410489
TI  - Label-free detection of bacterial RNA using polydiacetylene-based biochip.
AB  - We developed a simple and effective polydiacetylene-based, label-free multiplex
      DNA chip for the detection of various pathogenic microorganisms. A novel
      immobilization method of PDA vesicles on glass slides was exploited using alpha
      cyclodextrin (alpha-CD). The surface topography of the efficiently immobilized
      PDA vesicles was confirmed using scanning electron microscopy (SEM) and atomic
      force microscopy (AFM). Then, oligonucleotides complementary to rRNAs of three
      pathogenic bacteria were conjugated to the PDA vesicles. Finally, crude lysate of
      pathogenic bacteria was applied to the PDA biochip. The pathogenic bacteria were
      specifically detected by DNA-RNA hybridization in an hour. The new PDA sensor was
      effective in detecting multiple pathogenic bacteria easily and accurately without
      rigorous purification, amplification, and labeling of their genetic components.

PMID- 22410490
TI  - Harmonic generation of an obliquely incident ultrasonic wave in solid-solid
      contact interfaces.
AB  - The conventional acoustic nonlinear technique to evaluate the contact acoustic
      nonlinearity (CAN) at solid-solid contact interfaces (e.g., closed cracks), which
      uses the through-transmission of normally incident bulk waves, is limited in that
      access to both the inner and outer surfaces of structures for attaching pulsing
      and receiving transducers is difficult. The angle beam incidence and reflection
      technique, where both the pulsing and receiving transducers are located on the
      same side of the target, may allow the above problem to be overcome. However, in
      the angle incidence technique, mode-conversion at the contact interfaces as well
      as the normal and tangential interface stiffness should be taken into account.
      Based on the linear and nonlinear contact stiffness, we propose a theoretical
      model for the reflection of an ultrasonic wave angularly incident on contact
      interfaces. In addition, the magnitude of the CAN-induced second harmonic wave in
      the reflected ultrasonic wave is predicted. Experimental results obtained for the
      contact interfaces of A16061-T6 alloy specimens at various loading pressures
      showed good agreement with theoretical predictions. Such agreement proves the
      validity of the suggested oblique incidence model.

PMID- 22410491
TI  - Transplantation: Basal insulin therapy may reduce the risk of new-onset diabetes
      after renal transplantation.

PMID- 22410493
TI  - Prevention of contrast-induced AKI--the ongoing saga.
AB  - Comparisons of sodium chloride and sodium bicarbonate for the prevention of
      contrast-induced acute kidney injury have produced inconclusive results. A new
      study by Klima et al. shows that sodium chloride provides greater renal
      protection than does sodium bicarbonate following exposure to contrast medium.
      However, this finding should be interpreted with caution.

PMID- 22410492
TI  - Monocyte subpopulations and cardiovascular risk in chronic kidney disease.
AB  - Chronic microinflammation and its cellular hallmark, monocyte activation,
      contribute substantially to the tremendous burden of cardiovascular disease (CVD)
      in patients with chronic kidney diseases (CKD). Monocyte heterogeneity is widely
      acknowledged. Cell-surface expression of CD14 and CD16 defines three functionally
      and phenotypically distinct subsets of monocytes: classical (CD14(++)CD16(-))
      monocytes, intermediate (CD14(++)CD16(+)) monocytes, and nonclassical
      (CD14(+)CD16(++)) monocytes. A growing body of circumstantial evidence suggests
      that intermediate monocytes, in particular, contribute to the development of
      atherosclerosis in the general population as well as in patients with CKD.
      Intermediate monocytes express a unique pattern of chemokine receptors that have
      been implicated in atherogenesis. Moreover, this subset of monocytes is
      predisposed to secrete proinflammatory cytokines. Findings from epidemiological
      studies indicate that numbers of intermediate monocytes increase with worsening
      renal function, and that high cell counts predict adverse outcomes in patients
      undergoing dialysis as well as in patients at early stages of CKD. Based on
      laboratory and clinical data, intermediate monocytes are a promising therapeutic
      target for CVD in patients with CKD.

PMID- 22410494
TI  - Mineral metabolism outcomes with frequent hemodialysis.

PMID- 22410495
TI  - Venomous mammals: a review.
AB  - The occurrence of venom in mammals has long been considered of minor importance,
      but recent fossil discoveries and advances in experimental techniques have cast
      new light into this subject. Mammalian venoms form a heterogeneous group having
      different compositions and modes of action and are present in three classes of
      mammals, Insectivora, Monotremata, and Chiroptera. A fourth order, Primates, is
      proposed to have venomous representatives. In this review we highlight recent
      advances in the field while summarizing biochemical characteristics of these
      secretions and their effects upon humans and other animals. Historical aspects of
      venom discovery and evolutionary hypothesis regarding their origin are also
      discussed.

PMID- 22410497
TI  - Frequency and aetiology of dermatophytosis in children age 12 and under in the
      state of Amazonas, Brazil.
AB  - BACKGROUND: Few scientific studies have evaluated dermatophytosis among children
      in the state of Amazonas or in the greater northern region of Brazil. AIMS: The
      aim of this study was to research the frequency and aetiology of dermatophytosis
      in children age 12 and under, who were seen between March 1996 and November 2005
      at the Mycology Laboratory of the National Institute of Amazonian Research.
      METHODS: For mycological diagnoses, epidermal scales and/or hairs were used. A
      portion of this material was treated with potassium hydroxide for direct
      examination, and another portion was cultivated in Mycobiotic Agar for the
      isolation of dermatophytes. RESULTS: Of the 590 samples analysed, 210 showed
      positive diagnoses by direct examination and cultivation. Tinea capitis (153
      cases) was the most frequent type of dermatophytosis, and Trichophyton tonsurans
      (121 cases) was the most frequently isolated fungal agent. Tinea corporis was
      observed in 48 cases where the most frequently isolated fungal agent was also T.
      tonsurans (17 cases), and the corporal regions most affected were the face, arms
      and trunk. The laboratory confirmed tinea pedis in 6 cases, and the principal
      fungal agents isolated were Trichophyton rubrum (3) and Trichophyton
      mentagrophytes (3). The presence of tinea cruris was confirmed in 3 cases, and T.
      rubrum, T. tonsurans and Epidermophyton floccosum were isolated from these cases.
      CONCLUSIONS: The children examined were primarily affected by tinea capitis, and
      the main fungal agent for this dermatophytosis was T. tonsurans.

PMID- 22410496
TI  - Vacuolar protein sorting 35 Asp620Asn mutation is rare in the ethnic Chinese
      population with Parkinson's disease.
AB  - Vacuolar protein sorting 35 (VPS35) Asp620Asn mutation has been identified in
      late-onset familial Parkinson's disease (PD) patients of Swiss and Austrian
      descent as well as sporadic PD patients in the United States. In order to
      determine the contribution of VPS35 mutations in mainland Chinese PD patients and
      to better understand the association between VPS35 and PD, we sequenced all 17
      exons of VPS35 in 32 probands of presumed autosomal-dominant, late-onset familial
      PD and 35 normal controls. Meanwhile, we analyzed VPS35 Asp620Asn mutation in 512
      PD patients. A total of 371 subjects without neurological disorders from the same
      region in China were set as a control group. We did not find any VPS35 coding
      region mutation in 32 familial PD patients. VPS35 Asp620Asn mutation was either
      not found in 480 PD patients. Our results suggested that VPS35 Asp620Asn may be
      not associated with PD in Chinese population.

PMID- 22410498
TI  - Microscopy compared to culture for the diagnosis of tuberculosis in induced
      sputum samples: a systematic review.
AB  - BACKGROUND: Resource-limited settings rely on sputum examination using microscopy
      to diagnose tuberculosis (TB); however, the sensitivity of the test is poor and
      case detection rates are low. Sputum induction is proposed as a way to improve
      sample collection and enhance test sensitivity. OBJECTIVE: To undertake a
      systematic review of studies comparing microscopy and culture sensitivity in
      induced sputum samples. METHODS: We ran duplicate searches of databases (up to
      August 2011) and searchable websites of major human immunodeficiency virus (HIV)
      and TB conferences (up to November  2010) to identify studies comparing the
      performance of microscopy compared to culture on induced sputum samples, with
      culture as the reference standard. RESULTS: A total of 23 studies met our
      inclusion criteria. The overall success of the induction was high, ranging from
      76.4% (95%CI 68.5-83.2)  to 100% (95%CI 98.5-100), while adverse events
      associated with sputum induction were infrequent and mild. The sensitivity of
      microscopy compared to culture ranged from 0% to 100%; only eight studies
      reported on the species of mycobacterium isolated in culture. Yield was generally
      higher  for sputum induction compared to nasopharyngeal aspiration and gastric
      lavage, and compared equally well to bronchoalveolar lavage and physiotherapy.
      DISCUSSION: Sputum induction increases TB case detection and is useful for people
      who are negative on spontaneous smear microscopy or unable  to expectorate
      spontaneously. It is well-tolerated by children and adults, irrespective of HIV
      status, and can be used where culture is not available. The use of induced sputum
      samples with molecular tests, such as Xpert((r)) MTB/RIF, warrants further
      investigation.

PMID- 22410499
TI  - Structure elucidation of indole-indoline type alkaloids: a retrospective account
      from the point of view of current NMR and MS technology.
AB  - In this review our aim is to look back on how the structure elucidation of
      bisindoles, especially with focus placed on vinblastine and vincristine
      analogues, has evolved alongside with the development of MS and NMR over the last
      60 years from the perspective of our present-day use of state-of-the-art MS and
      NMR instrumentation and on the basis of our own accumulated views and experience
      in the field.

PMID- 22410500
TI  - Comparative determination of sibutramine as an adulterant in natural slimming
      products by HPLC and HPTLC densitometry.
AB  - A new validated method for the identification and quantification of the
      sibutramine was developed by HPTLC-densitometry at 225 nm and advantages and
      disadvantages compared with HPLC-FLD at 225 nm emission and 316 nm excitation.
      Both methods were applied to the analysis of three natural slimming products in
      the market for the quantitative analysis of illegally added sibutramine. HPTLC
      separations were performed on (20 cm * 10 cm) glass HPTLC plates coated with
      silica gel 60 F(254) using a mobile phase, n-hexane-acetone-ammonia (10:1:0.1,
      v/v/v). For HPLC analysis, a phenyl column (5.0 MUm, 150 mm * 4.6 mm, i.d.) and
      an isocratic mobile phase of acetonitrile-water-formic acid (pH 3.0; 0.19M)
      (45:55:0.78, v/v/v) was used. The calibration curve area versus concentration was
      found to be linear in the range of 250-2000 ng/spot(-1) and 5-200 MUg/ml for
      HPTLC and HPLC, respectively. Both methods were validated for accuracy,
      precision, linearity, selectivity, recovery and short term stability. As a
      conclusion, these methods were found to be useful for the routine analysis of
      illegally added sibutramine in the marketed products.

PMID- 22410501
TI  - Simultaneous determination of antidementia drugs in human plasma: procedure
      transfer from HPLC-MS to UPLC-MS/MS.
AB  - A previously developed high performance liquid chromatography mass spectrometry
      (HPLC-MS) procedure for the simultaneous determination of antidementia drugs,
      including donepezil, galantamine, memantine, rivastigmine and its metabolite NAP
      226-90, was transferred to an ultra performance liquid chromatography system
      coupled to a tandem mass spectrometer (UPLC-MS/MS). The drugs and their internal
      standards ([(2)H(7)]-donepezil, [(13)C,(2)H(3)]-galantamine, [(13)C(2),(2)H(6)]
      memantine, [(2)H(6)]-rivastigmine) were extracted from 250 MUL human plasma by
      protein precipitation with acetonitrile. Chromatographic separation was achieved
      on a reverse phase column (BEH C18 2.1 mm * 50 mm; 1.7 MUm) with a gradient
      elution of an ammonium acetate buffer at pH 9.3 and acetonitrile at a flow rate
      of 0.4 mL/min and an overall run time of 4.5 min. The analytes were detected on a
      tandem quadrupole mass spectrometer operated in positive electrospray ionization
      mode, and quantification was performed using multiple reaction monitoring. The
      method was validated according to the recommendations of international guidelines
      over a calibration range of 1-300 ng/mL for donepezil, galantamine and memantine,
      and 0.2-50 ng/mL for rivastimgine and NAP 226-90. The trueness (86-108%),
      repeatability (0.8-8.3%), intermediate precision (2.3-10.9%) and selectivity of
      the method were found to be satisfactory. Matrix effects variability was inferior
      to 15% for the analytes and inferior to 5% after correction by internal
      standards. A method comparison was performed with patients' samples showing
      similar results between the HPLC-MS and UPLC-MS/MS procedures. Thus, this
      validated UPLC-MS/MS method allows to reduce the required amount of plasma, to
      use a simplified sample preparation, and to obtain a higher sensitivity and
      specificity with a much shortened run-time.

PMID- 22410502
TI  - Risk analysis of analytical validations by probabilistic modification of FMEA.
AB  - Risk analysis is a valuable addition to validation of an analytical chemistry
      process, enabling not only detecting technical risks, but also risks related to
      human failures. Failure Mode and Effect Analysis (FMEA) can be applied, using a
      categorical risk scoring of the occurrence, detection and severity of failure
      modes, and calculating the Risk Priority Number (RPN) to select failure modes for
      correction. We propose a probabilistic modification of FMEA, replacing the
      categorical scoring of occurrence and detection by their estimated relative
      frequency and maintaining the categorical scoring of severity. In an example, the
      results of traditional FMEA of a Near Infrared (NIR) analytical procedure used
      for the screening of suspected counterfeited tablets are re-interpretated by this
      probabilistic modification of FMEA. Using this probabilistic modification of
      FMEA, the frequency of occurrence of undetected failure mode(s) can be estimated
      quantitatively, for each individual failure mode, for a set of failure modes, and
      the full analytical procedure.

PMID- 22410503
TI  - Increased IgA and IgM responses against gut commensals in chronic depression:
      further evidence for increased bacterial translocation or leaky gut.
AB  - BACKGROUND: Recently, we discovered that depression is accompanied by increased
      IgM and IgA responses directed against gram negative gut commensals. The aim of
      this study was to replicate these findings in a larger study group of depressed
      patients and to examine the associations between the IgA and IgM responses to gut
      commensals and staging of depression as well as the fatigue and somatic (F&S)
      symptoms of depression. METHODS: We measured serum concentrations of IgM and IgA
      against the LPS of gram-negative enterobacteria, i.e. Hafnia alvei, Pseudomonas
      aeruginosa, Morganella morganii, Pseudomonas putida, Citrobacter koseri, and
      Klebsiella pneumoniae in 112 depressed patients and 28 normal controls. The
      severity of F&S symptoms was measured using the Fibromyalgia and Chronic Fatigue
      Syndrome Rating Scale. RESULTS: The prevalences and median values of serum IgM
      and IgA against LPS of these commensals were significantly higher in depressed
      patients than in controls. The IgM levels directed against the LPS of these
      commensal bacteria were significantly higher in patients with chronic depression
      than in those without. The immune responses directed against LPS were not
      associated with melancholia or recurrent depression. There was a significant
      correlation between the IgA response directed against LPS and gastro-intestinal
      symptoms. DISCUSSION: The results indicate that increased bacterial translocation
      with immune responses to the LPS of commensal bacteria may play a role in the
      pathophysiology of depression, particularly chronic depression. Bacterial
      translocation may a) occur secondary to systemic inflammation in depression and
      intensify and perpetuate the primary inflammatory response once the commensals
      are translocated; or b) be a primary trigger factor associated with the onset of
      depression in some vulnerable individuals. The findings suggest that
      "translocated" gut commensal bacteria activate immune cells to elicit IgA and IgM
      responses and that this phenomenon may play a role in the pathophysiology of
      (chronic) depression by causing progressive amplifications of immune pathways.

PMID- 22410504
TI  - Dropout rate and associated factors in patients with bipolar disorders.
AB  - OBJECTIVES: Effective, long-term therapy for bipolar disorders is a critical goal
      of mental health care, but achieving this goal is complicated by numerous factors
      in real clinical settings. The aim of this study was to investigate dropout
      patterns and their associated factors in patients with bipolar disorders.
      METHODS: The study participants were 275 patients with DSM-IV bipolar disorders,
      receiving planned maintenance treatment among patients at the Mood Disorders
      Clinic of Seoul National University Bundang Hospital between January 2005 and
      December 2007. The rates of dropout in patients were prospectively examined for 3
      years. The factors affecting the dropouts were analyzed using a Cox regression
      model. RESULTS: The dropout rates were 10.9%, 20.4%, 24.7%, 33.8%, 44.0%, and
      50.2% at 1, 3, 6, 12, 24, and 36 months after treatment entry, respectively. The
      dropout rates increased rapidly during the first three months and slowed after 12
      months. Past psychotic symptoms (HR 0.523, 95% CI 0.339-0.807), longer illness
      duration (HR 0.975, 95% CI 0.955-0.966), past psychiatric diagnoses (bipolar
      disorder, HR 0.242, 95% CI 0.120-0.490; other axis I disorders 0.434, 95% CI
      0.268-0.701), and a past history of dropouts (HR 1.746, 95% CI 1.028-2.965)
      significantly influenced the time to dropout in bipolar patients. The main
      reasons for dropout were 'denial of therapeutic need' (34.8%) and 'lack of
      treatment efficacy' (23.2%). Dropout from the maintenance phase of treatment was
      mainly attributed to the patients' poor understanding of the effects of their
      treatment. CONCLUSION: A high early dropout rate for subjects with bipolar
      disorders was observed in this study, suggesting an increased risk for
      insufficient maintenance treatment. These results may support the role of
      psychoeducational approaches in enhancing adherence to treatment, as well as
      social approaches to improving public awareness. Following the early evaluation
      of a patient's concept of bipolar disorders, individualized psychoeducational
      strategies are necessary to improve the long-term outcomes for subjects with
      bipolar disorders.

PMID- 22410505
TI  - Peeking into the minds of troubled adolescents: the utility of polysomnography
      sleep studies in an inpatient psychiatric unit.
AB  - BACKGROUND: Sleep problems are commonly associated with the primary diagnostic
      criteria for many psychiatric disorders. Evidence suggests sleep disturbances may
      precede development of psychiatric disorders and the severity of psychopathology
      reflects the severity of sleep problems. Polysomnography (PSG) sleep studies in
      child and adolescent psychiatric populations, a particularly at risk group, has
      considerable value but has been more elusive requiring further investigation.
      METHODS: We performed a retrospective chart review of PSG sleep studies and
      psychiatrist evaluations of 106 adolescents aged 7-16 admitted to an involuntary
      adolescent psychiatric inpatient facility. RESULTS: Less than 5% of cases had
      mild/no sleep problems. Hyperarousal hallmarked this population, and severity of
      sleep disturbances trends with the severity of psychopathology. Inpatients with
      multiple psychiatric disorders had greater frequencies of insomnia, decreased
      sleep efficiency, and arousals from SWS (p<0.05). Inpatient's with self-harm
      behavior more frequently had elevated sleep onset latency (SOL), reduced
      efficiency, reduced SWS (p<0.05), increased REM, and reduced REM latency compared
      to inpatients with dysthymia and/or depression. LIMITATIONS: Lacking an a priori
      hypothesis, this study was explorative and uncontrolled for factors such as
      medications. This notwithstanding however, analysis indicates the majority of
      inpatients were taking cocktails that "should" alleviate sleep symptoms
      suggesting greater associations may prevail in unmedicated populations.
      CONCLUSIONS: This study attests to the potential clinical utility of PSG sleep
      studies in the management of adolescent psychiatric disorders and contributes to
      the body of evidence reputing the intimate connection between sleep problems and
      the development and perpetuation of psychopathology with public health
      implications.

PMID- 22410506
TI  - Evolution of perinatal depressive symptoms from pregnancy to two years postpartum
      in a low-risk sample: the MATQUID cohort.
AB  - BACKGROUND: Few studies have explored the evolution of perinatal depressive
      symptoms (PNDS) throughout the perinatal period. AIMS: To evaluate in a low-risk
      sample, whether different evolutive profiles of PNDS exist from pregnancy to 2
      years postpartum, and whether the subgroups differ regarding psychopathological
      and demographic characteristics. METHODS: In a prospective, longitudinal study
      from 8 months pregnancy to 2 years postpartum, repeated measures of PNDS using
      the CES-D were performed on a sample of 579 women at low-risk for PNDS. First,
      semiparametric mixture models were used to identify groups of women with distinct
      trajectories of PNDS. Second, multinomial logistic regressions were used to
      identify risk factors for each group. RESULTS: Four distinct trajectories of PNDS
      evolution were found: (i) 72% of the women never presented with clinically
      significant depressive symptoms; (ii) 4% presented with depressive symptoms only
      during the postnatal period; (iii) 21% presented with depressive symptoms
      throughout the follow-up period, with a higher intensity during pregnancy; (iv)
      3% presented with stable highly intense symptoms throughout the follow-up period.
      Psychosocial risk factors for PNDS were mainly identified in the patients of the
      third group, with an influence of socio-economical variables and anxiety traits.
      LIMITATIONS: The main limitations of the present study are the small size of the
      sample and the low level of risk for PNDS, so the results cannot be extrapolated
      to all types of populations. CONCLUSION: Different subtypes of evolutionary
      profiles of PNDS are found in a low-risk sample, and are associated with
      different profiles of risk factors.

PMID- 22410508
TI  - 49th National Conference, Indian Academy of Pediatrics, Gurgaon, January 19,
      2012.

PMID- 22410507
TI  - Early administration of systemic corticosteroids reduces hospital admission rates
      for children with moderate and severe asthma exacerbation.
AB  - STUDY OBJECTIVE: The variable effectiveness of clinical asthma pathways to reduce
      hospital admissions may be explained in part by the timing of systemic
      corticosteroid administration. We examine the effect of early (within 60 minutes
      [SD 15 minutes] of triage) versus delayed (>75 minutes) administration of
      systemic corticosteroids on health outcomes. METHODS: We conducted a prospective
      observational cohort of children aged 2 to 17 years presenting to the emergency
      department with moderate or severe asthma, defined as a Pediatric Respiratory
      Assessment Measure (PRAM) score of 5 to 12. The outcomes were hospital admission,
      relapse, and length of active treatment; they were analyzed with multivariate
      logistic and linear regressions adjusted for covariates and potential
      confounders. RESULTS: Among the 406 eligible children, 88% had moderate asthma;
      22%, severe asthma. The median age was 4 years (interquartile range 3 to 8
      years); 64% were male patients. Fifty percent of patients received systemic
      corticosteroids early; in 33%, it was delayed; 17% of children failed to receive
      any. Overall, 36% of patients were admitted to the hospital. Compared with
      delayed administration, early administration reduced the odds of admission by 0.4
      (95% confidence interval 0.2 to 0.7) and the length of active treatment by 0.7
      hours (95% confidence interval -1.3 to -0.8 hours), with no significant effect on
      relapse. Delayed administration was positively associated with triage priority
      and negatively with PRAM score. CONCLUSION: In this study of children with
      moderate or severe asthma, administration of systemic corticosteroids within 75
      minutes of triage decreased hospital admission rate and length of active
      treatment, suggesting that early administration of systemic corticosteroids may
      allow for optimal effectiveness.

PMID- 22410509
TI  - Path to polio eradication in India: a major milestone.

PMID- 22410510
TI  - Population level assessments of immunization--when more complex is better.

PMID- 22410511
TI  - Low serum magnesium and obesity--causal role or diet biomarker?

PMID- 22410512
TI  - Environmental exposures and childhood cancer.

PMID- 22410513
TI  - Retinopathy of prematurity promising newer modalities of treatment.
AB  - Retinopathy of prematurity (ROP) is a disorder of neonatal retinal
      vascularization. The incidence is increasing in developing countries like India
      in view of the rising numbers of preterm deliveries and improved neonatal care.
      Traditional modalities of treatment included cryotherapy and laser therapy, which
      were laborious and required special training. Hence, research is on way to find
      novel treatment modalities directed at various levels of pathogenesis for this
      blinding disease. We reviewed the published and unpublished literature on newer
      methods of ROP management. The pathogenesis of ROP has been studied with respect
      to the mediators of angiogenesis. Anti vascular endothelial growth factor (Anti
      VEGF) therapy has been extensively studied and the studies have demonstrated its
      promising role early stages of ROP. The role of Insulin like growth factor (IGF),
      Granulocyte colony stimulating factor (GCSF), and June kinases (JNK) inhibitors
      are being studied by various researchers across the world. Gene therapy holds
      promise in the reversal of ROP changes.

PMID- 22410514
TI  - Persistent earache due  to tonsillolith.
AB  - Tonsilloliths are rare dystrophic calcification formed as a result of chronic
      inflammation of the tonsils. Tonsilloliths tend to occur more commonly with
      increasing age and are relatively rare in children. We report a case of
      unilateral tonsilloliths in an eight-year-old boy, who presented with earaches
      and history of regurgitating tiny yellowish-white foul smelling pellets. The
      tonsilloliths were successfully removed under local anaesthesia following which
      the symptoms subsided.

PMID- 22410515
TI  - Corrosive tracheo-esophageal fistula following button battery ingestion.
AB  - We describe a case of corrosive tracheo-esophageal fistula following button
      battery ingestion in a 1-year old nonverbal pediatric patient. The delay in
      diagnosis was caused by failure to obtain correct history and failure to detect
      opacity of the battery in the neck at the first visit.  The large fistula was
      successfully treated with division and repair with non absorbable sutures, with
      interposition of strap muscles between separated trachea and esophagus.

PMID- 22410516
TI  - Interrupted aortic arch and aortopulmonary window associated with complete
      atrioventricular septal defect.
AB  - We report a rare case of a neonate with interrupted aortic arch, aortopulmonary
      window and complete atrioventricular septal defect. To the best of our knowledge,
      this unusual triad has not been previously described. The main question of the
      surgical strategy for CAVSD, in setting of associated defects, is to classify the
      CAVSD as balanced or unbalanced.

PMID- 22410517
TI  - Jejunal atresia in a neonate due to intrauterine intussusception.
AB  - We report a female neonate, who presented with abdominal distension and failure
      to pass meconium. Antenatal ultrasound at 32 weeks gestation and postnatal
      ultrasound on day1 suggested intestinal obstruction. During laparatomy, atresia
      of distal jejunum was found. The lumen of the distal segment contained an
      intussusceptum. Resection of the blind ends was done and end-to-end anastomosis
      was performed.

PMID- 22410518
TI  - Sporadic hemiplegic migraine.
AB  - We report a 4-year old boy with probable sporadic hemiplegic migraine. The
      present case did not fulfill the International Classification of Headache
      Disorders diagnostic criteria for the disease completely, as it is unclear
      whether the child had any headache or not. The differential diagnoses are
      discussed. The case is reported for its rarity and to increase awareness.

PMID- 22410519
TI  - Charcoal hemoperfusion for phenytoin intoxication.
AB  - Accidental ingestion of phenytoin can lead to severe neurological sequelae.
      Charcoal hemoperfusion decreases phenytoin levels but has never been reported
      before in children. We present a child with accidental ingestion of phenytoin who
      responded to charcoal hemoperfusion.

PMID- 22410520
TI  - Transfusion related acute lung injury in a child with leukemia.
AB  - Transfusion-related acute lung injury is a rare form of acute respiratory
      distress syndrome of possible immune etiology that develops immediately after a
      blood product transfusion. Clinicians need to be aware of this condition as
      prompt recognition and supportive management can prevent unwanted morbidity and
      mortality.

PMID- 22410521
TI  - Parathyroid carcinoma presenting as genu valgum.

PMID- 22410522
TI  - Congenital splenorenal shunt: a dilemma.

PMID- 22410523
TI  - Biliary atresia with cytomegalovirus.

PMID- 22410525
TI  - Biliary atresia and cytomegalovirus infection.

PMID- 22410526
TI  - Why quantity of diphtheria and pertussis vaccines is reduced for children 7 years
      onwards?

PMID- 22410528
TI  - Kawasaki disease in association with urinary tract infection.

PMID- 22410530
TI  - Hyperglycemia in PICU tread with caution.

PMID- 22410531
TI  - Dystrophic epidermolysis bullosa.

PMID- 22410532
TI  - Special issue on the Great East Japan Earthquake and the activities of members
      and alumni of the School of Medicine, Keio University.

PMID- 22410533
TI  - The first clinical trial in Tohoku University Hospital after the Great East Japan
      Earthquake: the heroic efforts of my friend, Professor Masashi Aoki.
AB  - The Great East Japan Earthquake of 2011 seriously jeopardized our collaborative
      research with Professor Masashi Aoki (Tohoku University School of Medicine) on
      the development of new therapies for amyotrophic lateral sclerosis (ALS) using
      hepatocyte growth factor. After the earthquake struck, Professor Aoki made a
      tremendous contribution to saving patients' lives and to recovering from the
      disastrous situation. Thanks to his strong leadership and support from many
      reliable colleagues, we could finally start new clinical trials for ALS patients.
      In this article, I wish to introduce Professor Aoki's heroic efforts.

PMID- 22410534
TI  - The Vision Van, a mobile eye clinic, aids relief efforts in tsunami-stricken
      areas.
AB  - In the wake of the devastating earthquake and tsunami of March 11, our group at
      Keio University worked diligently to bring the Vision Van, a mobile eye clinic,
      from Miami, Florida, to disaster areas where medicines, eyeglasses, and indeed
      all other ophthalmological supplies and services, were nonexistent, thereby
      assisting many tsunami survivors suffering from eye problems. This act was
      encouraging not only to the patients and those working in the disaster-hit areas
      but also to ophthalmologists who wanted to use their medical specialty to assist
      those in need.

PMID- 22410535
TI  - Mental health and psychosocial support after the Great East Japan Earthquake.
AB  - Since the Great East Japan Earthquake, Keio University School of Medicine has, at
      the request of the Tokyo Metropolitan Government, provided mental health and
      psychosocial support to those living in Soma City in Fukushima Prefecture. This
      report covers the types of support provided in Soma City and discusses previous
      studies that were used as the model for current support practice and the results
      gained from actual performance. Also included is a summary of the objectives that
      were or were not achieved for medical support compared with recommendations from
      previous studies. Furthermore, future directions for medical support are also
      discussed.

PMID- 22410536
TI  - The medical association activity and pediatric care after the earthquake disaster
      in Fukushima.
AB  - On March 11, 2011, a gigantic earthquake struck eastern Japan. Utilities such as
      electricity, water, gas and telecommunication were interrupted. In Koriyama, the
      City Hall collapsed and government administration offices had to be moved to a
      nearby baseball stadium that had been designed to include facilities for use
      during a pandemic. An operations center was set up in this stadium. As members of
      the Koriyama Medical Association, we following the disaster protocol and set up
      our operations center in the Koriyama Medical Care Hospital. One large hospital
      with 280 inpatients and another hospital with 150 inpatients had been heavily
      damaged. Transfer of those patients to other hospitals without the use of
      telecommunications was extremely difficult. Many doctors in member hospitals and
      clinics went out of their way to cooperate throughout the crisis. Up to 5,000
      people from the radiation evacuation zone were rushed to Koriyama. They stayed in
      schools and community centers, where we provided them with healthcare. Even in
      Koriyama, which is 60 km away from the Fukushima nuclear power plant, radiation
      levels were high, especially for the first few weeks. Citizens were advised to
      stay at home and keep their doors and windows closed. These drastic measures and
      frequent earthquake aftershocks were very stressful, especially for children. To
      help prevent children from developing posttraumatic stress disorder (PTSD), a
      project team composed of various groups caring for children was developed, and
      this team took action to protect children. Through these efforts we hoped to
      provide children with an appropriate environment to grow normally, even in a zone
      of persistent low-level radiation. We demonstrated once again that our members'
      long history of mutual assistance and cooperation with the administration was the
      main cornerstone to overcome the crisis.

PMID- 22410537
TI  - Nuclear disaster after the earthquake and tsunami of March 11.
AB  - We would like to explain the effects of radiation on human health and discuss the
      actual effects of the contamination with radioactive material present in Tokyo.
      Currently, external exposure doses are within the allowable range in Tokyo and
      will have no adverse health effects on adults or children. As for internal
      exposure doses, there will likely be no problems as regards our ordinary dietary
      intakes. However, hot spots of Cs-134, Sr-90 and others should be monitored
      further.

PMID- 22410538
TI  - Comparison of two large earthquakes: the 2008 Sichuan Earthquake and the 2011
      East Japan Earthquake.
AB  - Between August 15th and 19th, 2011, eight 5th-year medical students from the Keio
      University School of Medicine had the opportunity to visit the Peking University
      School of Medicine and hold a discussion session titled "What is the most
      effective way to educate people for survival in an acute disaster situation
      (before the mental health care stage)?" During the session, we discussed the
      following six points: basic information regarding the Sichuan Earthquake and the
      East Japan Earthquake, differences in preparedness for earthquakes, government
      actions, acceptance of medical rescue teams, earthquake-induced secondary
      effects, and media restrictions. Although comparison of the two earthquakes was
      not simple, we concluded that three major points should be emphasized to
      facilitate the most effective course of disaster planning and action. First, all
      relevant agencies should formulate emergency plans and should supply information
      regarding the emergency to the general public and health professionals on a
      normal basis. Second, each citizen should be educated and trained in how to
      minimize the risks from earthquake-induced secondary effects. Finally, the
      central government should establish a single headquarters responsible for
      command, control, and coordination during a natural disaster emergency and should
      centralize all powers in this single authority. We hope this discussion may be of
      some use in future natural disasters in China, Japan, and worldwide.

PMID- 22410539
TI  - Challenges for diagnosis and control of cystic hydatid disease.
AB  - This paper is based on the experience of the authors, with the aim to define the
      challenges for Echinococcus granulosus (E.g./CE) diagnosis and control for those
      countries that may now or in the future be contemplating control of hydatid
      disease. A variety of methods are available for diagnosis in humans but a
      universal gold standard is lacking. Diagnosis in definitive hosts can avoid
      necropsy by the use of methods such as coproantigen detection but test
      performance is variable between populations. A sylvatic cycle adds challenges in
      some countries and the epidemiology of the parasite in these hosts is poorly
      understood. Control by solely administering praziquantel to dogs is not effective
      in developing countries where the disease is endemic. Additional avenues to
      pursue include the instigation of participatory planning, use of an existing
      vaccination for intermediate hosts and development of a vaccine and long-acting
      anthelmitic implants for definitive hosts. Promoting public acceptance of control
      of the dog population by humane euthanasia and reduced reproduction is also
      essential.

PMID- 22410540
TI  - Environmental factors underlying spatial patterns of sand flies (Diptera:
      Psychodidae) associated with leishmaniasis in southern Sinai, Egypt.
AB  - Although Leishmania major is endemic in parts of the Sinai of Egypt, the ecology
      and distribution of Leishmania sand fly vectors in southern Sinai has not been
      well characterized. Accordingly, additional sand fly samples were obtained at 41
      sites in the southern Sinai region during 1996-1997, and analyzed to improve the
      characterization of risk of sand fly-borne pathogens. Using a Geographic
      Information System (GIS), species-specific spatial distributions that might
      suggest zoonotic cutaneous leishmaniasis (ZCL) risk areas were determined in
      relation to contextual environmental factors, including geology, hydrogeology,
      climate variables and elevation. Southern Sinai was characterized by a diverse
      sand fly fauna (eight Phlebotomus species), probably attributable to highly
      variable landscape and environmental factors. Phlebotomus alexandri, Phlebotomus
      kazeruni and Phlebotomus sergenti were widespread and abundant, Phlebotomus
      papatasi and Phlebotomus bergeroti were less frequent, and Phlebotomus arabicus,
      Phlebotomus major and Phlebotomus orientalis had highly restricted distributions.
      Logistic regression models indicated that elevation and climatic conditions were
      limiting determinants for the distributions of sand flies in southern Sinai.
      Based on the predicted distribution of P. papatasi, a recognized vector of L.
      major, about one-quarter of southern Sinai may be at high risk of ZCL. Risk areas
      for the suspected ZCL vector P. bergeroti had a more patchy distribution. Results
      suggest that future studies should include other factors related to vector
      abundance, vector competence, human population, and parasite and reservoir
      host(s) to produce more comprehensive ZCL transmission risk maps, thus helping in
      planning effective prevention and control strategies.

PMID- 22410541
TI  - Elimination of malaria in country Georgia.
AB  - Malaria is well known in Georgia since ancient times, causing national disasters
      with associated significant mortality and economic losses. By 1970 Georgia
      managed to reach complete and sustained elimination of the disease as a result of
      comprehensive anti-malaria measures undertaken in the country. However from the
      mid-1990s, economic collapse following disintegration of Soviet Union causing
      breakdown of important public health networks including anti-malaria preventive
      and control infrastructure resulted in gradual increase of malaria cases in the
      country with a peak of 437 and 474 cases in 2001 and 2002, respectively. From
      2000 two major anti-malaria efforts were carried out by National Center for
      Disease Control and Public Health, WHO and Global Fund to Fight AIDS,
      tuberculosis and malaria and as result of comprehensive and collaborative work in
      2010 the level of zero cases of local mosquito-borne malaria transmission was
      achieved and the country entered the elimination phase.

PMID- 22410543
TI  - Patient-reported outcomes in rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: In recent years, there has been increasing interest, as
      indicated by a growing number of citations in the medical literature, on the
      assessment of outcomes in patients with rheumatoid arthritis (RA) focusing on the
      patient's perspective. This article describes the domains of patient-reported
      outcomes (PROs), instruments for measuring responses, as well as the use of PRO
      in clinical trials with newer agents, including biologic agents. RECENT FINDINGS:
      At the 10th Outcome Measure in Rheumatology Clinical Trials (OMERACT) conference,
      several methodological issues about the choice of PRO domains, the development of
      instruments measuring these domains, and the methods for assessing response
      criteria were addressed. Composite domains like the RA impact of disease (RAID)
      score and core outcomes for the RA patient priorities for pharmacologic
      interventions (RAPP-PI) were introduced. Minimally clinically important
      differences in various PROs have been used to measure responsiveness to change in
      clinical trials. Many randomized clinical trials show significant improvements in
      PRO, such as the health assessment questionnaire disability index, and the
      medical outcomes study short form with effective treatment. SUMMARY: PRO has
      become an essential part when assessing patients with RA. This trend will likely
      continue into the future, in both clinical trials as well as clinical practice.

PMID- 22410542
TI  - Retention of an autologous endothelial layer on a bioprosthetic valve for the
      treatment of chronic deep venous insufficiency.
AB  - PURPOSE: Percutaneous transcatheter implantation of porcine small intestinal
      submucosa (SIS) bioprosthetic valves has been reported as a treatment for chronic
      deep venous insufficiency (CDVI). Endothelial progenitor outgrowth cells (EOCs),
      isolated from whole ovine blood, were evaluated as a source of in vitro
      autologous seeding for SIS endothelialization. Retention of the EOC monolayer was
      evaluated to test the feasibility of delivering an endothelialized SIS valve.
      MATERIALS AND METHODS: Twenty bioprosthetic venous valves were constructed from
      SIS sutured onto collapsible square stent frames and were seeded with ovine EOCs
      in vitro. Retention of the endothelial monolayer through valve loading and
      delivery (three valves), in vitro flow (three valves), and ex vivo flow (four
      valves) was evaluated with immunofluorescent staining and histologic analysis
      compared with paired unmanipulated control valves. In the ex vivo shunt loop,
      venous blood was pulled from an implanted dialysis catheter, through the valve,
      and returned to the sheep. RESULTS: Immunofluorescent staining of EOCs on the
      valves after in vitro seeding revealed a confluent monolayer (95.6% +/- 2.3%
      confluent) on each side of the valve. When examined by immunofluorescent
      staining, the endothelial monolayer remained intact after loading and delivery
      (97.1% +/- 1.7%) and when subjected to flow in the in vitro loop (96.0% +/-
      3.0%). Histologic analysis of the valves subjected to the ex vivo shunt loop
      revealed retention of the endothelial monolayer. CONCLUSIONS: Endothelial
      monolayers seeded on SIS were retained under loading and delivery, in vitro flow,
      and ex vivo flow. EOCs are a promising cell source for autologous
      endothelialization of bioprosthetic valves for the treatment of CDVI.

PMID- 22410544
TI  - Chronobiology and the treatment of rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: As circadian rhythms and biological signaling occur in a
      complex network with cyclical 24-h period interactions (chronobiology) between
      the central and the autonomic nervous systems, the endocrine glands and the
      immune system, this review will explore the involvement of this emerging network
      in the disease pathophysiology and management. RECENT FINDINGS: Recent advances
      regarding nocturnal hormones such as melatonin and prolactin that activate the
      nighttime immune response, and the successive rise of cortisol that dowregulates
      the ongoing immune reactivity very early in the morning, will be discussed within
      the circadian neuroendocrine immune network. In addition, the role of sleep and
      the daily distribution of body energy, which are important factors for the
      homoeostatic regulation of circadian physiological/pathological processes of the
      immune network will be reviewed.In chronic immune/inflammatory conditions such as
      rheumatoid arthritis (RA), stiffness and functional disability are evident in the
      early morning hours as under the chronic stress of the disease the nighttime
      adrenal cortisol production becomes insufficient to inhibit ongoing nocturnal
      immune/inflammatory activity. SUMMARY: Currently, the most advanced approach to
      optimizing the risk-benefit ratio for long-term glucocorticoid treatment in RA
      seems to be low-dose chronotherapy with modified nighttime release prednisone
      (release at 3 a.m.). A similar chronotherapeutical approach could also be
      effective with disease-modifying antirheumatic drugs such as methotrexate.

PMID- 22410545
TI  - Refractory disease in antineutrophil cytoplasmic antibodies associated
      vasculitis.
AB  - PURPOSE OF REVIEW: Induction treatment of antineutrophil cytoplasmic antibodies
      (ANCA) associated vasculitis (AAV) is not always successful and nonresponding
      patients are considered refractory. RECENT FINDINGS: Refractory disease should be
      subdefined to the treatment that was received. Cyclophosphamide refractory AAV
      occurs in up to 5% of patients. Many more patients develop contraindications to
      cyclophosphamide or relapse frequently. The latter two patient groups might also
      benefit from treatment used for cyclophosphamide refractory AAV. SUMMARY: The
      most promising drug for treating refractory AAV is rituximab.

PMID- 22410546
TI  - The economic burden of tuberculosis care for patients and households in Africa: a
      systematic review.
AB  - OBJECTIVES: To summarise the state of knowledge on the economic impact and
      consequences of tuberculosis (TB) diagnosis and treatment for patients/households
      in Africa, and to highlight any weaknesses in the work conducted to date.
      METHODS: We systematically searched for published  articles in English between
      1990 and June 2010 in eight databases and the World Health Organization (WHO)
      website. Broad search terms were used ('tuberculosis' OR 'tuberculosis/HIV' AND
      'costs' AND 'Africa'). Only studies that reported any costs  of TB care for
      patients/households were retained. All costs were converted to 2009 USD in
      accordance with WHO cost analysis guidelines. RESULTS: Overall, 11 articles from
      eight countries met the inclusion criteria. Only one study met all the quality
      criteria for a cost-of-illness study;  most of the studies focused on urban
      populations, reported incomplete (pre-diagnostic/average) costs, and did not
      report coping costs. Mean patient pre-diagnostic costs varied between US$36 and
      US$196, corresponding to respectively 10.4% and 35% of their annual income.
      Average  patient treatment costs ranged between US$3 and US$662, corresponding to
      0.2-30% of their annual income. Pre-diagnostic household costs accounted for 13%
      and 18.8% of patients' annual household income, while total household treatment
      costs ranged between US$26 and  US$662, accounting for 2.9-9.3% of annual
      household income; 18-61% of patients received financial assistance from outside
      their household to cope with the cost of TB care. CONCLUSION: The average
      patient's/household's pre-diagnostic costs for TB care were catastrophic.  More
      properly designed studies are needed among different populations throughout
      Africa.

PMID- 22410547
TI  - A comparison of the neuroendocrine mechanisms underlying the initiation of the
      preovulatory LH surge in the human, Old World monkey and rodent.
AB  - As recognized for decades, the role of the rodent hypothalamus in timing the LH
      surge is deterministic and mediated by a GnRH discharge that is generated by an
      obligatory interaction in the preoptic area (POA) between a threshold level of
      estradiol and a circadian neural signal: a view consistent with contemporary
      kisspeptinocentric models of the estrous cycle. In higher primates, generation of
      the LH surge is emancipated from control by the POA. Woman represents the
      exemplar of the system in higher primates, as the LH surge appears to unfold in
      the absence of a midcycle GnRH discharge being generated instead by facilitatory
      interaction between a pulsatile GnRH input to the pituitary and an action of
      ovarian estradiol. The neurobiology of GnRH pulse generation is only beginning to
      emerge but from a translational perspective this aspect of hypothalamic function
      is critical for understanding the human menstrual cycle and how it may be
      perturbed.

PMID- 22410549
TI  - Familiarity of environmental sounds is used to establish auditory rules.
AB  - This study addressed the extraction of long-term sound familiarity as a higher
      order feature of complex, environmental sounds. Physically variable, familiar
      animal sounds and spectrotemporally matched, unfamiliar control sounds were
      presented. Participants ignored the acoustic stimuli. Infrequent deviant sounds
      violated the familiarity status established by the standard sounds, but no
      regularity on the basis of physical features. In the auditory event-related
      potential, deviants elicited a negative-going deflection over parietal scalp
      areas around 230 ms. This effect occurred for familiar deviants among unfamiliar
      standards and for unfamiliar deviants among familiar standards. The results
      indicate the establishment of an auditory regularity based on sound familiarity.
      This reflects the extraction of sound familiarity outside the focus of attention.

PMID- 22410548
TI  - Quantitative analysis of gray and white matter in Williams syndrome.
AB  - Williams syndrome is a developmental disorder with a genetic basis, which results
      in an uneven cognitive profile with relatively strong language skills and
      severely impaired visuospatial abilities. To better understand the brain
      structure underlying this profile, we compared individuals with Williams syndrome
      with controls using multimodal neuroimaging data and new analytic methods
      (diffeomorphic mapping and atlas-based analysis). People with Williams syndrome
      had basal ganglia atrophy, while the fusiform, the medium temporal gyri, and the
      cerebellar cortex were relatively preserved. The right superior longitudinal
      fasciculus, the left frontooccipital fasciculus, the caudate, and the cingulum
      demonstrated increased fractional anisotropy, whereas the corticospinal tract
      revealed decreased values. These findings may be linked to the uneven cognitive
      profile evident in Williams syndrome.

PMID- 22410550
TI  - Image inversion spectral-domain optical coherence tomography optimizes choroidal
      thickness and detail through improved contrast.
AB  - PURPOSE: This study was conducted to determine whether there were significant
      differences in choroidal thickness, contrast, outer choroidal vessel (OCV), and
      choroidal-scleral junction (CSJ) visualization in inverted versus upright
      spectral-domain optical coherence tomography (SD-OCT). METHODS: Images were
      captured on Bioptigen SD-OCT, Zeiss Cirrus HD-OCT, and Heidelberg Spectralis in
      42 eyes of 21 healthy subjects. Average choroidal thickness across a fovea
      centered 4-mm segment was determined with MATLAB. Quantitative measures of
      choroidal contrast were measured and CSJ assessed by applying a score of 0 to 3.
      OCV was determined by counting choroidal vessels >= 200 MUm. RESULTS: Mean
      choroidal thickness was greater in inverted versus upright images captured by
      Bioptigen (P <= 0.003) and Spectralis (P <= 0.015). Choroidal thickness varied
      significantly between the three machines (P < 0.05). Contrast was higher in
      inverted versus upright images captured by Bioptigen (P <= 0.02) and Spectralis
      (P < 0.001), but not in Cirrus (P > 0.10, both observers). CSJ score was highest
      in the following: Spectralis inverted = Spectralis EDI > Cirrus upright >
      Bioptigen inverted. Mean OCV was highest in Spectralis inverted mode. CONCLUSION:
      The most favorable modes to visualize CSJ and OCV are the Spectralis EDI,
      Spectralis inverted, Cirrus upright, and Bioptigen inverted. These modes
      demonstrate the highest outer choroidal contrast and choroidal thickness
      measurements. Choroidal thickness cannot be compared between machines due to
      conversion factor differences. Future studies and construction of automated
      segmentation and detection software should take these benefits and pitfalls into
      account.

PMID- 22410551
TI  - Beta-adrenoreceptor agonism influences retinal responses to hypoxia in a model of
      retinopathy of prematurity.
AB  - PURPOSE: In a mouse model of oxygen-induced retinopathy (OIR), a well-established
      model of retinopathy of prematurity (ROP), blocking beta-adrenoreceptors (beta
      ARs), and, in particular, beta2-ARs, counteracts retinal responses to hypoxia. In
      the present work, we determined the effects of the beta-AR agonist isoproterenol
      on retinal angiogenesis and beta-AR signaling to better clarify the role of
      sympathetic transmission in ROP. METHODS: Isoproterenol was administered
      subcutaneously. Protein kinase A activity was determined by a colorimetric assay
      to assess drug effectiveness. Blood pressure and heart-to-body weight ratio were
      measured. Vascular endothelial growth factor (VEGF) and norepinephrine were
      measured with ELISA. Retinal neovascularization was assessed by CD31
      immunohistochemistry. beta-AR-coupled adenylyl cyclase (AC) activity was measured
      with a competition assay. beta-ARs, G-protein-coupled receptor kinase (GRK)2, and
      beta-arrestins were determined by Western blot. Association of beta-arrestins
      with beta2-ARs was assessed by immunoprecipitation. RESULTS: Isoproterenol
      induced modulation of protein kinase A activity suggests that the drug was
      effective at the receptor level. Isoproterenol did not affect cardiovascular
      parameters, but decreased retinal levels of VEGF and reduced pathogenic
      neovascularization, likely through an influence on sympathetic transmission. In
      fact, isoproterenol downregulated beta2-AR expression, recovered the hypoxia
      induced increase in beta-AR-coupled AC activity, and increased GRK2 and beta
      arrestins, which promote beta-AR desensitization through the uncoupling of G
      protein-coupled receptors from G proteins. Immunoprecipitation studies
      demonstrated that beta-AR desensitization involved beta2-ARs. CONCLUSIONS: Our
      findings suggest that hypoxia-induced retinal neovascularization depends at least
      in part on increased sympathetic transmission, as reduction of sympathetic drive
      by agonist-induced beta2-AR desensitization inhibits some of the hallmarks of
      OIR.

PMID- 22410552
TI  - Evaluation of SNPs on chromosome 2p with primary open angle glaucoma in the South
      Indian cohort.
AB  - PURPOSE: Glaucoma comprises a heterogeneous group of optic neuropathies with a
      complex genetic basis. It is the second leading cause of irreversible blindness
      in the world. This study investigates the association of SNPs on chromosome 2p
      with primary open angle glaucoma (POAG) in a Southern Indian population. METHODS:
      Case-control analysis was performed using 220 unrelated POAG cases and 220 age
      matched unaffected controls recruited through the Aravind Eye Hospital and its
      outlying clinics. Five SNPs (rs1533428, rs12994401, rs10202118, rs11125375, and
      rs11889995) on chromosome 2p were evaluated in these two groups and genotyped
      using Taq Man SNP genotyping assay. Statistical analysis was performed using the
      SVS program package by Golden Helix to identify the distributions of allele and
      genotype frequencies, Fisher exact test P values, and odds ratios and to check
      Hardy-Weinberg equilibrium. RESULTS: Among the five SNPs screened, SNP
      rs10202118, showed a P = 0.026 for the basic allelic test, P = 0.004 for the
      genotypic test, and P = 0.0014 for the recessive model. The second suggestive
      marker was rs11125375, which also showed P = 0.033 for the recessive model. The
      associated SNPs formed a common disease haplotype. The remaining three SNPs
      showed insignificant association in this study population. CONCLUSIONS: This was
      the first study to demonstrate the association of SNPs on chromosome 2p in
      patients with POAG in the Indian population. The two tagging SNPs (rs10202118 and
      rs11125375) on chromosome 2p are the most likely sites underlying the significant
      association with POAG in this study population.

PMID- 22410553
TI  - AMG 386, a selective angiopoietin 1/2-neutralizing peptibody, inhibits
      angiogenesis in models of ocular neovascular diseases.
AB  - PURPOSE: To determine whether systemic treatment with AMG 386, a selective
      angiopoietin 1/2-neutralizing peptibody, inhibits neovascular processes in animal
      models of ocular disease. METHODS: AMG 386 was tested in a laser-induced
      choroidal neovascularization (CNV) model in monkeys using fluorescein
      angiography. The biodistribution of (125)I-AMG 386 was determined in cynomolgus
      monkeys by whole-body autoradiography and radioanalysis of ocular tissues. A
      murine retinopathy of prematurity (ROP) model was used to examine the effect of
      AMG 386 on established and newly formed retinal vessels, either as a single agent
      or when combined with VEGF inhibition.AMG 386 pharmacokinetics were evaluated in
      each model. RESULTS: In the CNV model, AMG 386 significantly decreased
      fluorescent angiographic leakage and reduced fibroplasia, indicating an impaired
      healing response consistent with angiogenesis blockade. Radiolabeled AMG 386 was
      widely distributed across ocular tissues, with highest concentrations in the
      choroid, cornea, retinal pigmented epithelium, iris/ciliary body, and sclera. In
      the ROP model, AMG 386 prevented pathologic retinal angiogenesis when
      administered from P8 to P16 but transiently impeded regression of these abnormal
      vessels when administered from P17 to P23. Combining AMG 386 with VEGF inhibition
      led to cooperative prevention of retinal angiogenesis in this model. No AMG 386
      related ocular toxicities occurred, and no treatment-related clinical
      observations were made in any of the studies. CONCLUSIONS: In this study, AMG 386
      inhibited angiogenesis in animal models of CNV and ROP, supporting investigation
      of AMG 386 for the treatment of ocular neovascular diseases in the clinical
      setting.

PMID- 22410554
TI  - TMP prevents retinal neovascularization and imparts neuroprotection in an oxygen
      induced retinopathy model.
AB  - PURPOSE: To evaluate the effects of tetramethylpyrazine (TMP) on retinal
      neovascularization (NV) and neuroprotection in an oxygen-induced retinopathy
      (OIR) model. METHODS: Neonatal C57BL/6J mice were subjected to 75% oxygen from
      postnatal day 7 (P7) to P12 and then returned to room air. TMP (200 mg/kg) or
      normal saline was given daily from P12 to P17. Immunostaining, HE staining, TUNEL
      assay, and RT-PCR were used to assess the effects of TMP on retinal neurovascular
      repair. RESULTS: TMP effectively prevented pathologic NV and accelerated
      physiologic revascularization by enhancing the formation of endothelial tip cells
      at the edges of the repairing capillary networks and preserving the astrocytic
      template in the avascular retina. TMP also prevented morphologic changes and
      significantly decreased TUNEL-positive cells in the avascular retina by rescuing
      neurons such as amacrine, rod bipolar, horizontal, and Muller cells. In TMP
      treated mice retinas, there was a less obvious loss of amacrine cell bodies and
      their distinct bands; the number of both rod bipolar and horizontal cell bodies,
      as well as the density of their dendrites in the outer plexiform layer, was
      greater than that in OIR control mice. TMP not only decreased the loss of
      alignment of Muller cell bodies and distortion of processes but reduced the
      reactive expression of GFAP in Muller cells. Furthermore, HIF-1alpha and VEGF
      mRNA expression were downregulated in TMP-treated mice retinas. CONCLUSIONS: TMP
      improved neurovascular recovery by preventing NV and protecting retinal astroglia
      cells and neurons from ischemia-induced cell death partially due to its
      downregulation of HIF-1alpha and VEGF mRNA expression.

PMID- 22410555
TI  - Incorporating risk factors to improve the assessment of rates of glaucomatous
      progression.
AB  - PURPOSE: To present and evaluate a new method of integrating risk factors into
      the analysis of rates of visual field progression in glaucoma. METHODS: The study
      included 352 eyes of 250 glaucoma patients followed up for an average of 8.1 +/-
      3.5 years. Slopes of change over time were evaluated by the mean deviation (MD)
      from standard automated perimetry. For each eye, the follow-up time was divided
      into two equal periods: the first half was used to obtain the slopes of change
      and the second period was used to test the predictions. Slopes of change were
      calculated with two methods: the conventional approach of ordinary least squares
      (OLS) linear regression and a Bayesian regression model incorporating information
      on risk factors and presence of progressive optic disc damage on
      stereophotographs. The mean square error (MSE) of the predictions was used to
      compare the predictive performance of the different methods. RESULTS: Higher mean
      IOP, thinner central corneal thickness (CCT), and presence of progressive optic
      disc damage were associated with faster rates of MD change. Incorporation of risk
      factor information into the calculation of individual slopes of MD change with
      the Bayesian method resulted in better prediction of future MD values than with
      the OLS method (MSE: 4.31 vs. 8.03, respectively; P < 0.001). CONCLUSIONS: A
      Bayesian regression model incorporating structural and risk factor information
      into the estimation of glaucomatous visual field progression resulted in more
      accurate and precise estimates of slopes of functional change than the
      conventional method of OLS regression. (ClinicalTrials.gov number, NCT00221897.).

PMID- 22410556
TI  - Glaucoma diagnostic ability of quadrant and clock-hour neuroretinal rim
      assessment using cirrus HD optical coherence tomography.
AB  - PURPOSE: The aim of this study was to investigate the glaucoma diagnostic ability
      of quadrant and clock-hour neuroretinal rim assessment by Cirrus HD spectral
      domain optical coherence tomography (OCT). METHODS: Eighty eyes of 80 glaucoma
      patients and 80 eyes of 80 healthy subjects were enrolled. Peripapillary retinal
      nerve fiber layer (RNFL) thickness was measured by Cirrus HD-OCT. Quadrant and
      clock-hour rim areas and thicknesses were obtained from optic nerve head images
      and 360 degrees  circumferential rim thickness curve of Cirrus HD-OCT,
      respectively. Area under receiver operating characteristic curves (AUCs) and
      sensitivities of RNFL thicknesses, rim areas, and rim thicknesses at a 90%
      specificity level were calculated. RESULTS: Quadrant and clock-hour rim area and
      thickness showed good diagnostic ability for glaucoma in all areas (AUCs, 0.877
      0.969; sensitivities, 67.5%-96.3%). When the AUCs of RNFL thicknesses, rim areas,
      and rim thicknesses were compared, no significant difference was found in global
      area and superior and inferior quadrants (P > 0.05). However, in nasal and
      temporal quadrants, rim area and thickness had greater AUCs (AUCs, 0.919-0.945;
      sensitivities, 82.5%-86.3%) than RNFL thickness (AUCs, 0.749-0.776;
      sensitivities, 12.5%-33.8%; P < 0.001). Eyes with moderate to advanced glaucoma
      (mean deviation < -6 dB) had thinner RNFL than mild glaucoma (mean deviation >= 
      6 dB) in global area, superior, inferior, and temporal quadrants (P < 0.003); rim
      area and thickness showed no significant difference in all areas (P > 0.003).
      CONCLUSIONS: Neuroretinal rim assessment in nasal and temporal areas by Cirrus HD
      OCT may enhance glaucoma diagnostic ability. RNFL and rim changes measured by
      Cirrus HD-OCT may be different according to the stages of glaucomatous damage.

PMID- 22410557
TI  - Nerve growth factor promotes endothelial progenitor cell-mediated angiogenic
      responses.
AB  - PURPOSE: In response to ischemia, retinal neuronal cells express nerve growth
      factor (NGF), which can be proangiogenic. Endothelial progenitor cells (EPCs) can
      participate with the resident vasculature to promote angiogenesis. We postulated
      that NGF may stimulate CD34+ EPCs to convert to an angiogenic phenotype. METHODS:
      Human CD34+ cells and human retinal endothelial cells (HRECs) were used to
      examine the effect of NGF on key steps associated with neovascularization. CD34+
      cells and HRECs were stimulated with NGF (1 to 4 pM) for 24, 48, and 72 hours.
      Cell migration was measured using a modified Boyden chamber assay. Expression of
      the receptor for the cytokine stromal derived growth factor 1 (SDF-1), CXCR-4,
      was assessed by flow cytometry. In vitro angiogenesis was tested using a three
      dimensional (3D) extracellular matrix with HRECs/CD34+ cell cocultures. NGF
      receptor activation was assessed by western analysis. RESULTS: NGF promoted
      proliferation of CD34+ cells but not HRECs. Pretreatment of CD34+ cells with NGF
      increased CXCR-4 expression in CD34+ cells, resulting in enhanced migration to
      SDF-1 (P < 0.0001). The enhanced tubule-forming effect of NGF in HRECs was
      further potentiated by coculture with NGF-pretreated CD34+ cells (P < 0.01). The
      beneficial effect of NGF was blocked (P < 0.0001) by the ERK inhibitor PD98059.
      In both CD34+ and HRECs, NGF increased phosphorylation of neurotrophic tyrosine
      kinase receptor type 1 (TrkA) receptor by ERK1 activation (P < 0.01).
      CONCLUSIONS: Our in vitro results suggest that NGF released from ischemic nerves
      in vivo may contribute to the "angiogenic switch" by stimulating the angiogenic
      behavior of CD34+ cells while minimally affecting resident retinal endothelial
      cells.

PMID- 22410559
TI  - Nanoscale topographic and biomechanical studies of the human internal limiting
      membrane.
AB  - PURPOSE: The purpose of this article was to create a nanometer scale topographic
      and biomechanical profile of the human internal limiting membrane (ILM) under
      native conditions. METHODS: ILMs from the posterior pole of postmortem human eyes
      were prepared as flat mounts and investigated by atomic force microscopy (AFM)
      under physiological conditions. Structural analysis was complemented by
      transmission electron microscopy. RESULTS: Average thickness of the fully
      hydrated, native ILMs was 3488 +/- 460 nm. Thickness variations from 100 nm to
      4326 nm characterized the fovea, which displayed a craterlike morphology. Outside
      the fovea, thickness distribution was uniform. Although mean ILM thicknesses were
      similar, standard deviation was higher on the retinal than on the vitreal side,
      indicating greater roughness. Average ILM stiffness was more than fivefold higher
      on the retinal than on the vitreal side (227 vs. 44 kPa). CONCLUSIONS: A detailed
      topographical and nanomechanical profile of native human ILM was generated using
      AFM. Thickness values were significantly higher than in previous studies because
      of the preservation of native conditions. Both thickness and stiffness showed
      marked variations around the fovea but were relatively uniform outside the foveal
      area. Interestingly, the foveal ILM displayed a craterlike morphological
      appearance with four distinct layers separated by comparatively steep thickness
      increments. ILM stiffness was considerably higher on the retinal than on the
      vitreal side. AFM opens new possibilities for investigating native basement
      membranes under physiological and pathological conditions. Transmission electron
      microscopy revealed higher extracellular matrix protein density on the retinal
      than on the vitreal side.

PMID- 22410558
TI  - Blood-derived human iPS cells generate optic vesicle-like structures with the
      capacity to form retinal laminae and develop synapses.
AB  - PURPOSE: We sought to determine if human induced pluripotent stem cells (iPSCs)
      derived from blood could produce optic vesicle-like structures (OVs) with the
      capacity to stratify and express markers of intercellular communication. METHODS:
      Activated T-lymphocytes from a routine peripheral blood sample were reprogrammed
      by retroviral transduction to iPSCs. The T-lymphocyte-derived iPSCs (TiPSCs) were
      characterized for pluripotency and differentiated to OVs using our previously
      published protocol. TiPSC-OVs were then manually isolated, pooled, and cultured
      en masse to more mature stages of retinogenesis. Throughout this stepwise
      differentiation process, changes in anterior neural, retinal, and synaptic marker
      expression were monitored by PCR, immunocytochemistry, and/or flow cytometry.
      RESULTS: TiPSCs generated abundant OVs, which contained a near homogeneous
      population of proliferating neuroretinal progenitor cells (NRPCs). These NRPCs
      differentiated into multiple neuroretinal cell types, similar to OV cultures from
      human embryonic stem cells and fibroblast-derived iPSCs. In addition, portions of
      some TiPSC-OVs maintained their distinctive neuroepithelial appearance and
      spontaneously formed primitive laminae, reminiscent of the developing retina.
      Retinal progeny from TiPSC-OV cultures expressed numerous genes and proteins
      critical for synaptogenesis and gap junction formation, concomitant with the
      emergence of glia and the upregulation of thrombospondins in culture.
      CONCLUSIONS: We demonstrate for the first time that human blood-derived iPSCs can
      generate retinal cell types, providing a highly convenient donor cell source for
      iPSC-based retinal studies. We also show that cultured TiPSC-OVs have the
      capacity to self-assemble into rudimentary neuroretinal structures and express
      markers indicative of chemical and electrical synapses.

PMID- 22410560
TI  - Creatine transporter immunolocalization in aged human and detached retinas.
AB  - PURPOSE: To identify the distribution of creatine transporter (CRT) in the aged
      human retina and how this expression pattern is modified after retinal
      detachment. METHODS: An affinity-purified antibody raised against the CRT was
      used in the immunohistochemical investigation. The anti-CRT antibody was
      colocalized with neuronal markers (calbindin, parvalbumin, Islet-1, calretinin,
      GAD67, Go-alpha), glia markers (glutamine synthetase, glial fibrillary acid
      protein), and a blood vessel basal membrane marker (laminin). Confocal microscopy
      was used to visualize the labeling patterns in retinal sections. The level of CRT
      expression was determined in the retina using a semiquantification method.
      RESULTS: Immunohistochemical assessment of CRT expression in the normal aged
      retina revealed strong labeling in photoreceptor synaptic terminals and in inner
      and outer segments. Labeling was also observed on subpopulations of amacrine
      cells and ganglion cells as well as in the outer and inner plexiform layers. CRT
      labeling was observed in blood vessels, although was absent in glial cells. In
      retinal detachment, the CRT labeling pattern was maintained, although there was
      an apparent decrease in labeling in inner retina and an increase in CRT
      expression in photoreceptors. CONCLUSIONS: CRT is expressed in areas of intense
      metabolic activity, such as photoreceptors, selected cells in the inner retina,
      and sites of creatine transport into the retina (inner retinal blood vessels and
      retinal pigment epithelium). The absence of CRT to Muller cells harmonizes with
      the concept that glial cells are a biosynthetic source of creatine but not a
      source of creatine to other retinal neurons. The increased immunolabeling of CRT
      localized to the outer retina in retinal detachment suggests a regional metabolic
      remodeling occurring in photoreceptor cells.

PMID- 22410561
TI  - Influence of clinically invisible, but optical coherence tomography detected,
      optic disc margin anatomy on neuroretinal rim evaluation.
AB  - PURPOSE: We previously demonstrated that most eyes have regionally variable
      extensions of Bruch's membrane (BM) inside the clinically identified disc margin
      (DM) that are clinically and photographically invisible. We studied the impact of
      these findings on DM- and BM opening (BMO)-derived neuroretinal rim parameters.
      METHODS: Disc stereo-photography and spectral domain optical coherence tomography
      (SD-OCT, 24 radial B-scans centered on the optic nerve head) were performed on 30
      glaucoma patients and 10 age-matched controls. Photographs were colocalized to SD
      OCT data such that the DM and BMO could be visualized in each B-scan. Three
      parameters were computed: (1) DM-horizontal rim width (HRW), the distance between
      the DM and internal limiting membrane (ILM) along the DM reference plane; (2) BMO
      HRW, the distance between BMO and ILM along the BMO reference plane; and (3) BMO
      minimum rim width (MRW), the minimum distance between BMO and ILM. Rank-order
      correlations of sectors ranked by rim width and spatial concordance measured as
      angular distances between equivalently ranked sectors were derived. RESULTS: The
      average DM position was external to BMO in all quadrants, except
      inferotemporally. There were significant sectoral differences among all three rim
      parameters. DM-HRW and BMO-HRW sector ranks were better correlated (median rho =
      0.84) than DM-HRW and BMO-MRW (median rho = 0.55), or BMO-HRW and BMO-MRW (median
      rho = 0.60) ranks. Sectors with the narrowest BMO-MRW were infrequently the same
      as those with the narrowest DM-HRW or BMO-HRW. CONCLUSIONS: BMO-MRW quantifies
      the neuroretinal rim from a true anatomical outer border and accounts for its
      variable trajectory at the point of measurement.

PMID- 22410562
TI  - Scanning laser polarimetry reveals status of RNFL integrity in eyes with optic
      nerve head swelling by OCT.
AB  - PURPOSE: Optical coherence tomography (OCT) shows retinal nerve fiber layer
      (RNFL) thickening in optic nerve head (ONH) swelling, but does not provide
      information on acute axonal disruption. It was hypothesized that scanning laser
      polarimetry (SLP) compared with OCT might reveal the status of axon integrity and
      visual prognosis in acute RNFL swelling. METHODS: Threshold perimetry, OCT, and
      SLP were used to prospectively study eyes with papilledema (24), optic neuritis
      (14), nonarteritic anterior ischemic optic neuropathy (NAION) (21), and ONH
      swelling (average RNFL value by OCT was above the 95th percentile of controls at
      presentation). Regional RNFL was judged reduced if the quadrant measurement was
      below the fifth percentile of controls. RESULTS: At presentation, average RNFL by
      OCT was similar for eyes with papilledema and NAION (P = 0.97), and reduced for
      optic neuritis. Average RNFL by SLP was slightly increased for papilledema and
      optic neuritis, and reduced for NAION (P = 0.02) eyes. The RNFL by SLP was
      reduced in at least one quadrant in 1 eye with papilledema, 1 eye with optic
      neuritis, and in 13 eyes with NAION. In NAION eyes, quadrants with reduced SLP
      had corresponding visual field loss that did not recover. By one month, eyes with
      NAION showed RNFL thinning by OCT (7/17 eyes) and by SLP (14/16 eyes) in contrast
      to optic neuritis (by OCT, 0/12, P = 0.006; and by SLP, 1/12, P = 0.0004).
      CONCLUSIONS: OCT and SLP revealed different aspects of RNFL changes associated
      with ONH swelling. OCT revealed thickening due to edema. SLP revealed a decrease
      in retardance in eyes with axonal injury associated with visual field loss, which
      is unlikely to recover.

PMID- 22410563
TI  - Corneal neurotoxicity due to topical benzalkonium chloride.
AB  - PURPOSE: The aim of this study was to determine and characterize the effect of
      topical application of benzalkonium chloride (BAK) on corneal nerves in vivo and
      in vitro. METHODS: Thy1-YFP+ neurofluorescent mouse eyes were treated topically
      with vehicle or BAK (0.01% or 0.1%). Wide-field stereofluorescence microscopy was
      performed to sequentially image the treated corneas in vivo every week for 4
      weeks, and changes in stromal nerve fiber density (NFD) and aqueous tear
      production were determined. Whole-mount immunofluorescence staining of corneas
      was performed with antibodies to axonopathy marker SMI-32. Western immunoblot
      analyses were performed on trigeminal ganglion and corneal lysates to determine
      abundance of proteins associated with neurotoxicity and regeneration.
      Compartmental culture of trigeminal ganglion neurons was performed in Campenot
      devices to determine whether BAK affects neurite outgrowth. RESULTS: BAK-treated
      corneas exhibited significantly reduced NFD and aqueous tear production, and
      increased inflammatory cell infiltration and fluorescein staining at 1 week (P <
      0.05). These changes were most significant after 0.1% BAK treatment. The extent
      of inflammatory cell infiltration in the cornea showed a significant negative
      correlation with NFD. Sequential in vivo imaging of corneas showed two forms of
      BAK-induced neurotoxicity: reversible neurotoxicity characterized by axonopathy
      and recovery, and irreversible neurotoxicity characterized by nerve degeneration
      and regeneration. Increased abundance of beta III tubulin in corneal lysates
      confirmed regeneration. A dose-related significant reduction in neurites occurred
      after BAK addition to compartmental cultures of dissociated trigeminal ganglion
      cells. Although both BAK doses (0.0001% and 0.001%) reduced nerve fiber length,
      the reduction was significantly more with the higher dose (P < 0.001).
      CONCLUSION: Topical application of BAK to the eye causes corneal neurotoxicity,
      inflammation, and reduced aqueous tear production.

PMID- 22410564
TI  - Corneal and retinal effects of ultraviolet-B exposure in a soft contact lens
      mouse model.
AB  - PURPOSE: To investigate the lipid and DNA oxidative stress as well as corneal and
      retinal effects after ultraviolet B (UV-B) exposure in mice, with or without
      silicon hydrogel soft contact lenses (SCL). METHODS: Twenty-eight C57BL6-strain
      male mice were divided into four groups: group I, control group with no SCL (SCL
      [-]) and no UV-B exposure (UV-B [-]); group II, senofilcon A SCL (senofilcon [+])
      with UV-B exposure (UV-B [+]); group III, lotrafilcon A SCL (lotrafilcon [+])
      with UV-B exposure (UV-B [+]); and group IV, no SCL (SCL [-]), but with UV-B
      exposure (UV-B [+]). All mice except group I received UV-B exposure for 5 days
      for a total dose of 2.73 J/cm(2). All mice underwent tear hexanoyl-lysine (HEL)
      and tear cytokine ELISA measurements, and fluorescein and rose bengal corneal
      staining before and after UV-B exposure. Corneal specimens underwent
      immunohistochemistry staining with CD45, HEL, 4-hydroxynonenal (4-HNE), and 8
      hydroxy-2'-deoxyguanosine (8-OHdG) antibodies and evaluation with electron
      microscopy. RESULTS: All mice without SCL but exposed to UV-B developed corneal
      edema, ulcers, or epithelial damage compared with mice with senofilcon A SCL and
      exposure to UV-B. Tear HEL and cytokine levels significantly increased in mice
      without SCL after UV-B exposure. Immunohistochemistry showed a significantly
      higher number of cells positively stained for CD45, 8-OHdG, HEL, and 4-HNE in the
      corneas of mice without SCLs compared with those with senofilcon A after UV-B
      exposure. CONCLUSION: Silicon hydrogel SCL showed corneal and retinal protective
      effects, owing to UV blocking properties, against oxidative stress-related
      membrane lipid and cellular DNA damage.

PMID- 22410565
TI  - Involvement of plasminogen activator inhibitor-1 in the pathogenesis of atopic
      cataracts.
AB  - PURPOSE: Further to our previous report of a genetic association between
      interferon-gamma (IFN-gamma) receptor 1 gene and atopic cataract, we investigated
      the roles of plasminogen activator inhibitor-1 (PAI-1), a fibrosis-related, IFN
      gamma downstream molecule, in the pathogenesis of atopic cataracts. METHODS:
      Cultured lens epithelial cells (LECs) were stimulated by IFN-gamma and quantified
      by PAI-1 mRNA/protein expression. PAI-1 and TGF-beta mRNA expression was
      quantified using cDNA samples obtained from the lens epithelium of atopic
      cataract patients (n = 7) and of senile cataract patients (n = 8). The anterior
      capsules obtained from atopic cataracts (n = 9) were immunostained with anti-PAI
      1 and anti-alpha smooth muscle actin (alpha-SMA) antibodies. PAI-1 gene
      expression was knocked down by PAI-1 siRNA, and alpha-SMA expression was examined
      under TGF-beta1 stimulation. Expression of alpha-SMA was examined as a
      pathological hallmark of anterior subcapsular cataracts, commonly observed in
      atopic cataracts. RESULTS: The IFN-gamma stimulation induced PAI-1 mRNA/protein
      expression in the LECs from 24 to 48 hours after stimulation. The expression of
      PAI-1 mRNA and TGF-beta1 mRNA was significantly higher in the cDNA samples
      obtained from the atopic cataracts than those obtained from the senile cataracts.
      PAI-1-positive immunostaining was observed at the fibrotic lesion of the atopic
      cataracts, and alpha-SMA-positive myofibroblasts were observed at the vicinity of
      the PAI-1-positive lesion in all nine samples examined. PAI-1 gene knockdown
      resulted in reduced alpha-SMA expression in the LECs. CONCLUSIONS: The findings
      of this study suggest that the IFN-gamma, PAI-1, and TGF-beta1 are involved in
      the pathophysiology of atopic cataracts.

PMID- 22410566
TI  - In situ autofluorescence visualization of human trabecular meshwork structure.
AB  - PURPOSE: To characterize the three-dimensional (3-D) structure of the human
      trabecular meshwork (TM) by two-photon excited (TPEF) autofluorescence (AF) and
      optical sectioning without conventional histologic embedding and sectioning.
      METHODS: Viable human ex vivo explants of the anterior chamber angle containing
      the aqueous humor drainage tissue in situ were imaged by TPEF to localize AF and
      Hoechst 33342 nuclear fluorescence. An autofluorescent marker in Schlemm's Canal
      (SC) aided SC situ visualization. En face and orthogonal views of the TM were
      generated. RESULTS: In the innermost uveal TM, AF signals outlined an intricate 3
      D network of fine branching beams with large openings between the beams. In the
      adjacent corneoscleral TM, beams were thicker and coalesced as plate-like
      structures with pore-like openings. Linear and coiled AF fibers were visible on
      the background AF of beams. Deeper, in the external TM, this organization changed
      to fine fiber arrays orientated in the tissue's longitudinal axis, reminiscent of
      the cribriform plexus of the juxtacanalicular TM (JCT). In the outermost JCT, AF
      of fine fibers was sparse, then undetectable as optical sections approached the
      inner wall of SC. Cell nuclei were closely associated with the TM structural
      extracellular matrix. CONCLUSIONS: We have used TPEF and optical sectioning to
      exploit AF as a useful method to visualize the structure of the human
      conventional aqueous drainage pathway in situ. Ancillary nuclear staining allowed
      cell association with the AF structures to be seen. This approach revealed a
      unique 3-D perspective of the TM that is consistent with known TM structural
      characteristics.

PMID- 22410567
TI  - Conjugate adaptation of smooth pursuit during monocular viewing in strabismic
      monkeys with exotropia.
AB  - PURPOSE: Humans and monkeys are able to adapt their smooth pursuit output when
      challenged with consistent errors in foveal/parafoveal image motion during
      tracking. Visual motion information from the retina is known to be necessary for
      guiding smooth pursuit adaptation. The purpose of this study is to determine
      whether retinal motion signals delivered to one eye during smooth pursuit produce
      adaptation in the fellow eye. We tested smooth pursuit adaptation during
      monocular viewing in strabismic monkeys with exotropia. METHODS: To induce smooth
      pursuit adaptation experimentally, we used a step-ramp tracking with two
      different velocities (adaptation paradigm), where the target begins moving at one
      speed (25 degrees /s) for first 100 ms and then changes to a lower speed (5
      degrees /s) for the remainder of the trial. Typically, 100 to 200 trials were
      used to adapt the smooth pursuit response. Control trials employing single speed
      step-ramp target motion (ramp speed = 25 degrees /s) were used before and after
      adaptation paradigm to estimate adaptation. RESULTS: The magnitude of adaptation
      as calculated by percentage change was not significantly different (P = 0.53) for
      the viewing (mean, 40.3% +/- 5.9%) and the nonviewing (mean, 39.7% +/- 6.2%) eyes
      during monocular viewing conditions, even in cases with large angle (18 degrees 
      20 degrees ) strabismus. CONCLUSIONS: Our results indicate that animals with
      strabismus retain the ability to produce conjugate adaptation of smooth pursuit.
      Therefore, we suggest that a single central representation of retinal motion
      information in the viewing eye drives adaptation for both eyes equally.

PMID- 22410568
TI  - In vivo human choroidal vascular pattern visualization using high-speed swept
      source optical coherence tomography at 1060 nm.
AB  - PURPOSE: To investigate the retinal and choroidal vascular pattern, structure,
      and thickness using high-speed, high axial resolution, swept-source optical
      coherence tomography (SS-OCT) at 1060 nm, demonstrating enhanced penetration
      through all choroidal layers. METHODS: An ophthalmic SS-OCT system was developed
      operating at 57,000 A-lines/s with 5.9 MUm axial resolution and was used to
      collect 3D images with scanning angles up to ~70 degrees  * 35 degrees . The
      similar features were observed in the choroidal layers by imaging three healthy
      volunteers. En face images, extracted at different depths, capture features of
      the retinal and choroidal vasculature networks and substructure. Retinal and
      choroidal thicknesses were measured over scanning angles of ~14 degrees  * 14
      degrees , yielding retinal and choroidal thickness maps. RESULTS: The retinal
      layers, choriocapillaris (CC), Sattler's layer (SL), Haller's layer (HL), and the
      lamina suprachoroid layer (LSL) were delineated in 2D sagittal tomograms. The
      sagittal tomograms and en face reflectance images over a 2-cm(2) field of view
      captured the paraoptic, lateral and medial distal short posterior ciliary artery
      (SPCA) branches as well as the two lateral and medial long posterior ciliary
      arteries (LPCAs). En face images in the HL revealed the superotemporal,
      inferotemporal, superonasal, and inferonasal major choroidal vessels.
      CONCLUSIONS: High-speed, high-resolution SS-OCT centered at 1060 nm enables
      retinal and choroidal vasculature networks visualization, including retina
      vessels, posterior ciliary artery (PCA) branches, and venous vascular patterns.
      This technology offers diagnostic opportunities by monitoring change in these
      networks, substructure, and retinal and choroidal thicknesses during disease
      initiation and progression.

PMID- 22410569
TI  - Multigene methylation analysis of ocular adnexal MALT lymphoma and their
      relationship to Chlamydophila psittaci infection and clinical characteristics in
      South Korea.
AB  - PURPOSE: We investigated the aberrant promoter methylation status of known or
      suspected tumor suppressor genes in ocular adnexal lymphoma (OAL) and the
      possible association with clinical characteristics and Chlamydophila psittaci
      infection. METHODS: Thirty-five cases of ocular adnexal mucosa-associated
      lymphoid tissue (MALT) lymphoma cases were examined for the methylation status of
      nine genes using methylation-specific PCR and for the detection of C. psittaci
      DNA using PCR. The medical records were reviewed retrospectively. Patient
      demographics, clinical characteristics including the response of the lymphoma to
      the therapy, and C. psittaci infection status were evaluated for possible
      association with methylation frequencies. RESULTS: CpG island methylation in nine
      genes was variously found as follows; DAPK (94.3%), ECAD (77.1%), MT1G (48.6%),
      THBS1 (37.1%), RAR-beta (31.4%), p16 (20%), MGMT (5.7%), p14 (0%), and RASSF1A
      (0%). Methylation was not observed in any of 13 control cases. C. psittaci DNA
      was observed in 25 (75.8%) of 33 patients with available tumor tissues, and ECAD
      hypermethylation was significantly higher in C. psittaci-positive cases (P =
      0.041). Promoter hypermethylation status was not correlated with clinical
      characteristics. CONCLUSIONS: Aberrant CpG island methylation of tumor suppressor
      genes is a frequent event in ocular adnexal MALT lymphoma. In particular, high
      frequencies of DAPK and ECAD methylation may be strongly correlated with ocular
      adnexal MALT lymphomagenesis in South Korea. Furthermore, ECAD hypermethylation
      is closely associated with C. psittaci infection, which may shed light on the
      mechanisms of bacterium-induced oncogenesis.

PMID- 22410571
TI  - Peripheral fundus autofluorescence is increased in age-related macular
      degeneration.
AB  - PURPOSE: To evaluate peripheral fundus autofluorescence (FAF) in patients with
      AMD. METHODS: A consecutive series of 71 normal eyes, 71 eyes with neovascular
      AMD having received anti-VEGF treatment, and 43 eyes with untreated AMD were
      investigated. In all subjects, wide-field FAF imaging was performed, applying a
      wide-field scanning laser ophthalmoscope. FAF was quantified by image analysis
      software after defining peripheral and perifoveal central measurement zones with
      a grid scheme; age correction was performed by regression model. RESULTS: Fundus
      autofluorescence increased with age not only in the perifoveal retinal area, but
      also in the retinal periphery. For age-corrected measurements, peripheral FAF was
      significantly increased for both, treated and untreated AMD groups compared with
      normal subjects. No significant difference was observed in peripheral FAF between
      AMD eyes having received anti-VEGF treatment and those without treatment. Age
      corrected normal FAF in the retinal center differed significantly from the anti
      VEGF-treated group (P < 0.01), but not the untreated AMD group. Age-corrected
      peripheral FAF irregularity, defined as the standard deviation in the measurement
      field, was significantly increased in both AMD groups compared with normal
      subjects. CONCLUSIONS: Detection of peripheral in addition to central FAF may
      provide additional information potentially helpful to detect and monitor the
      development of AMD. No differences in autofluorescence were observed in the
      retinal periphery between anti-VEGF-treated and untreated eyes.

PMID- 22410570
TI  - DNA methylation is associated with altered gene expression in AMD.
AB  - PURPOSE: Age-related macular degeneration (AMD) is the leading cause of blindness
      in the elderly. Evidence suggests oxidative stress plays a role in the disease.
      To assess the potential contribution of epigenetic regulation of antioxidant
      genes relevant to AMD pathogenesis, we evaluated DNA methylation, a tissue
      specific genetic modulation that affects gene expression. METHODS: Using the
      Infinium HumanMethylation27 Illumina platform, we performed DNA bisulfite
      sequencing to compare the methylation status in postmortem retina pigment
      epithelium (RPE)/choroid between patients with AMD and age-matched controls. Gene
      expression was assessed with the Affymetrix Exon Array. TaqMan gene expression
      assays were used for relative quantification (RT-PCR) confirmation of the
      expression array results: Glutathione S-transferase isoform mu1 (GSTM1) and mu5
      (GSTM5) promoter methylation was confirmed by CpG island bisulfite
      pyrosequencing. To assess protein levels and localization, we used Western
      analysis, immunohistochemistry, and immunofluorescence with murine and human
      samples. RESULTS: The mRNA levels of GSTM1 and GSTM5 were significantly reduced
      in AMD versus age-matched controls in RPE/choroid and neurosensory retina (NSR),
      which corresponded to hypermethylation of the GSTM1 promoter. mRNA and protein
      levels were decreased (RPE to a greater extent than NSR) in AMD postmortem
      samples, irrespective of age. Immunohistochemistry and immunofluorescence confirm
      the presence of the enzymes in the NSR and RPE. CONCLUSIONS: Comparison of DNA
      methylation, together with mRNA levels, revealed significant differences between
      AMD versus normal retinas. The evidence presented suggests that GSTM1 and GSTM5
      undergo epigenetic repression in AMD RPE/choroid, which may increase
      susceptibility to oxidative stress in AMD retinas.

PMID- 22410573
TI  - The effect of low and ultra-low dosages Thymoglobulin on peripheral T, B and NK
      cells in kidney transplant recipients.
AB  - INTRODUCTION: Rabbit Anti-Thymocyte Globulin (r-ATG) is a polyclonal antibody
      preparation, used to prevent and treat acute rejection episodes after organ
      transplantation. However, despite more than 40 years of clinical use, the optimal
      dose of r-ATG is still not defined. To find a better balance between efficacy and
      infectious complications, we embarked on a controlled study and monitored the
      effect of low and ultra-low dosages Thymoglobulin (Genzyme) on peripheral T, B,
      and NK cells. PATIENTS AND METHODS: Kidney transplant recipients received either
      0.5 mg/kg, 1.0 mg/kg or 2.0 mg/kg on the first 3 consecutive days post
      transplantation. Thus, total doses were 1.5 mg/kg, 3.0 mg/kg and 6.0 mg/kg. A
      total of 40 patients were enrolled, including 11 controls. All patients were
      treated with Prednisolon, Advagraf (Astellas) and Mycophenolate Mofetil (Roche).
      T (CD3+), B (CD19+) and NK (CD3-CD16+56+) cells were analyzed by flow cytometry.
      Baseline cell counts were compared to forty age and sex matched healthy persons.
      Post-transplantation cell counts of the 3 Thymoglobulin groups were compared to
      the 11 control patients, who received no induction therapy. RESULTS: Absolute
      numbers of T, B, and NK cells were comparable in all patients pre
      transplantation, but T and B cells were lower than in healthy persons (p=0.007
      and p=0.0003, Mann Whitney test). In the first week, T cells and NK cells were
      significantly lower in all Thymoglobulin groups compared to controls. B cells
      were not affected. One month after Thymoglobulin NK cells had returned to control
      numbers in all groups, while T cells had already recovered to control counts in
      the 1.5 mg/kg group. During follow-up, T cells in the 3.0mg/kg group also
      returned to control values, but at one year the patients in the 6.0 mg/kg group
      still had significantly lower T cells (p=0.03). Patient and graft survival,
      rejection and infection incidence and renal function did not differ between
      groups. CONCLUSION: Patients with end stage renal disease have significantly
      lower peripheral T and B cell counts than healthy persons. (Ultra-) low
      Thymoglobulin schedules deplete peripheral lymphocytes in a dose dependent way.
      Knowledge of the duration of this depletion contributes to finding the optimal
      immunosuppressive strategy for kidney transplant recipients.

PMID- 22410572
TI  - Lactate-H+ transport is a significant component of the in vivo corneal
      endothelial pump.
AB  - PURPOSE: To confirm the expression of monocarboxylate transporters (MCT) 1, 2,
      and 4 in rabbit CE and to test the hypothesis that cellular buffering contributed
      by HCO3-, NBCe1, and carbonic anhydrase (CA) activity facilitates lactate-H+
      efflux thereby controlling corneal hydration in vivo. METHODS: MCT1-4 expression
      of rabbit endothelium was examined by Western blotting and immunofluorescence
      staining. Lactate-induced acidification (LIA) was measured in perfused CE in the
      presence and absence of HCO3- and acetazolamide (ACTZ) using tissue treated with
      siRNA specific to MCT1, 2, and 4. Corneal thickness and lactate concentration
      were measured in New Zealand White rabbits treated with the topical CA inhibitor
      Azopt, and from eyes that were injected intracamerally with ouabain, disodium
      4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS), and shRNA specific to the
      1Na+:2HCO3- cotransporter NBCe1. RESULTS: MCT1 and MCT4 are localized to the
      lateral membrane, while MCT2 is apical. Cell pH measurements showed LIA in
      response to 40 mM lactate in bicarbonate free (BF) Ringer's that was inhibited by
      niflumic acid and by MCT siRNA knockdown, and significantly reduced in the
      presence of HCO3-. Lactate-dependent proton flux in vitro was not significantly
      greater in the presence of HCO3- or reduced by ACTZ. However, when active
      transport, NBCe1, or CA activity was disrupted in vivo, corneal edema ensued and
      was associated with significant corneal lactate accumulation. CONCLUSIONS: MCT1,
      2, and 4 are expressed in rabbit CE on both the apical and basolateral surfaces
      and function to transport lactate-H+. Lactate-H+ flux is facilitated by active
      transport, HCO3- transport and CA activity, disruption of which causes corneal
      edema in vivo and indicates that facilitation of lactate efflux is a component of
      the endothelial pump.

PMID- 22410574
TI  - "Inverse" synthesis of polymer bioconjugates using soluble supports.
AB  - Well-defined cleavable or non-cleavable soluble polystyrene supports were
      prepared by atom transfer radical polymerization and utilized for the iterative
      synthesis of functional hexapeptides. This approach allowed rapid and efficient
      liquid phase synthesis of peptide-polymer conjugates.

PMID- 22410575
TI  - The effects of temporary ischemia in partial nephrectomy on renal functional
      outcomes: how can effects best be estimated, and can they be mitigated?

PMID- 22410577
TI  - Novel discovery of lamellar papillae on the grooming organ in Synsphyronus
      (Garypidae: Pseudoscorpiones).
AB  - The chelicerae, the first pair of appendages in Chelicerata, exhibit
      morphological and functional variation across arachnid orders. The two-segmented
      chelicerae of pseudoscorpions serve multiple functions including grooming,
      courtship, and grasping prey. Scanning electron microscopy was used to
      investigate structures found on the chelicera; the serrulae interiores and
      exteriores, grooming organs, were given special attention. Functional analogies
      were made between the cheliceral structures documented in pseudoscorpions and
      those found in other arthropods. The novel discovery of vestitural papillae and a
      patch of elongate papillae on the serrula exterior are reported. The focal taxon
      for the study is Synsphyronus (Garypidae), an Australasian genus.

PMID- 22410578
TI  - Endogenous RNA viruses of plants in insect genomes.
AB  - Endogenous viral elements (EVEs) derived from RNA viruses with no DNA stage are
      rare, especially those where the parental viruses possess single-strand positive
      sense (ssRNA+) genomes. Here we provide evidence that EVEs that share a sequence
      similarity to ssRNA+viruses of plants are integrated into the genomes of a number
      of insects, including mosquito, fruit flies, bees, ant, silkworm, pea aphid,
      Monarch butterfly, and wasps. A preliminary phylogenetic analysis places these
      EVEs as divergent relatives of the Virgaviridae and three currently unclassified
      plant viral species.

PMID- 22410580
TI  - Alzheimer disease: Treatment of Alzheimer disease in Down syndrome.

PMID- 22410579
TI  - The genetics of Tourette syndrome.
AB  - Tourette syndrome is a complex neurological disorder that usually becomes evident
      between 4 and 18 years of age. The disorder is characterized by chronic motor and
      phonic tics, often with a variety of behavioural comorbidities; in particular,
      attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and
      impulse control disorder. The cause of Tourette syndrome is poorly understood.
      Although environmental factors are proposed to have a role, genetic factors are
      thought to be the primary contributors to the pathogenesis of this disorder.
      However, identification of the causative gene mutations or risk alleles has
      proved to be difficult. Early studies on the genetics of Tourette syndrome
      focused on multigenerational lineages and suggested Mendelian inheritance, but
      subsequent segregation analyses point to a more-complex inheritance pattern. A
      monogenic inheritance model has been proposed following the identification of
      rare genetic mutations associated with the Tourette syndrome phenotype. Although
      no specific mutations have found to directly cause Tourette syndrome, genetic
      findings may enable identification of the affected pathways, and could lead to
      the development of new treatment strategies. In this Review, we provide an
      overview of the genetics of Tourette syndrome and highlight how this knowledge
      has improved our understanding of the possible pathogenic mechanisms of this
      neurological disorder.

PMID- 22410581
TI  - Epilepsy: Issues with antiepileptic drug use in HIV-infected patients.

PMID- 22410584
TI  - Sounds can alter the perceived direction of a moving visual object.
AB  - Auditory temporal or semantic information often modulates visual motion events.
      However, the effects of auditory spatial information on visual motion perception
      were reported to be absent or of smaller size at perceptual level. This could be
      caused by a superiority of vision over hearing in reliability of motion
      information. Here, we manipulated the retinal eccentricity of visual motion and
      challenged the previous findings. Visual apparent motion stimuli were presented
      in conjunction with a sound delivered alternately from two horizontally or
      vertically aligned loudspeakers; the direction of visual apparent motion was
      always perpendicular to the direction in which the sound alternated. We found
      that the perceived direction of visual motion could be consistent with the
      direction in which the sound alternated or lay between this direction and that of
      actual visual motion. The deviation of the perceived direction of motion from the
      actual direction was more likely to occur at larger retinal eccentricities. These
      findings suggest that the auditory and visual modalities can mutually influence
      one another in motion processing so that the brain obtains the best estimates of
      external events.

PMID- 22410583
TI  - Antithrombotics for secondary prevention of noncardioembolic ischaemic stroke.
AB  - Antiplatelet therapy is more effective than anticoagulation for the prevention of
      noncardioembolic ischaemic stroke. The choice of antiplatelet regimen, however,
      remains contentious. Recent controversies regarding aspirin resistance and the
      optimal dosing of aspirin, as well as recognition of the variable bioactivation
      of clopidogrel, have added further confusion to the debate. The American Heart
      Association (AHA) and American Stroke Association (ASA) recently released their
      third joint guideline in the past 5 years on secondary stroke prevention. The
      European Stroke Organisation has published three guidelines on this issue since
      2000. These frequent updates have been necessary because of rapidly accumulating
      data from clinical trials. Careful consideration of the sometimes confusing trial
      results reveals that the 2011 AHA-ASA guidelines are correct in no longer
      specifying a 'preferred' antiplatelet regimen from among the choices recently
      studied. This recommendation does not, however, mean that all antiplatelet
      regimens should be considered equal. This Review discusses the various
      antiplatelet regimens, and the trials that led to the rapid evolution of the
      guidelines for secondary prevention of ischaemic stroke.

PMID- 22410585
TI  - Effects of reference objects and extra-retinal information about pursuit eye
      movements on curvilinear path perception from retinal flow.
AB  - We have previously shown that when traveling on a circular path, observers use
      the rotation in the retinal velocity field for path curvature estimation and
      recover their path of forward travel relative to their perceived instantaneous
      heading (L. Li, & J. C. K. Cheng, 2011). Here, we examined the contribution of
      reference objects and extra-retinal information about pursuit eye movements to
      curvilinear path perception. In Experiment 1, the display simulated an observer
      traveling on a circular path over a textured ground with and without tall posts
      while looking at a fixed target on the future path, along heading, or along a
      fixed axis in the world. We found that reference objects did not help path
      perception. In Experiment 2, extra-retinal signals about pursuit eye movements
      were introduced in two viewing conditions: one that corresponded to the natural
      case of traveling on a circular path when the body orientation is aligned with
      the instantaneous heading and one that corresponded to the unnatural case of
      traveling when the body orientation is fixed relative to the world. We found that
      extra-retinal signals support accurate path perception only for the natural case
      of self-motion when the body orientation is aligned with heading such that
      pursuit compensation helps stabilize the heading in the body-centric coordinate
      system.

PMID- 22410582
TI  - Modifiable factors that alter the size of the hippocampus with ageing.
AB  - The hippocampus is particularly vulnerable to the neurotoxic effects of obesity,
      diabetes mellitus, hypertension, hypoxic brain injury, obstructive sleep apnoea,
      bipolar disorder, clinical depression and head trauma. Patients with these
      conditions often have smaller hippocampi and experience a greater degree of
      cognitive decline than individuals without these comorbidities. Moreover,
      hippocampal atrophy is an established indicator for conversion from the normal
      ageing process to developing mild cognitive impairment and dementia. As such, an
      important aim is to ascertain which modifiable factors can have a positive effect
      on the size of the hippocampus throughout life. Observational studies and
      preliminary clinical trials have raised the possibility that physical exercise,
      cognitive stimulation and treatment of general medical conditions can reverse age
      related atrophy in the hippocampus, or even expand its size. An emerging concept-
      the dynamic polygon hypothesis--suggests that treatment of modifiable risk
      factors can increase the volume or prevent atrophy of the hippocampus. According
      to this hypothesis, a multidisciplinary approach, which involves strategies to
      both reduce neurotoxicity and increase neurogenesis, is likely to be successful
      in delaying the onset of cognitive impairment with ageing. Further research on
      the constellation of interventions that could be most effective is needed before
      recommendations can be made for implementing preventive and therapeutic
      strategies.

PMID- 22410587
TI  - Trends and challenges in tuberculosis in a medium-sized southern European
      setting.
AB  - Trends in tuberculosis (TB) admissions over 40 years at the Infectious Diseases
      Clinic of Perugia University Hospital, Perugia, Italy, show that in the last
      decade non-Italian TB case admissions outweighed those of Italians, with a large
      number of cases from Eastern Europe (25.2%) and  Africa (23.4%). Non-Italians
      tended to be younger and were generally new pulmonary TB cases, and drug
      resistance was also more common. Overall, the number of multidrug-resistant cases
      increased. Only one case occurred in a native-born Italian, and five of seven
      cases had newly diagnosed TB.  In low TB incidence settings such as Perugia,
      Italy, TB prevention and control programmes for the foreign-born need to be
      reinforced.

PMID- 22410586
TI  - A randomized controlled trial comparing intrathecal morphine with transversus
      abdominis plane block for post-cesarean delivery analgesia.
AB  - BACKGROUND: Intrathecal morphine is an effective analgesic post-cesarean
      delivery; however, it may be contraindicated or unsuitable in some patients. We
      compared the efficacy and side effects of intrathecal morphine with an ultrasound
      guided transversus abdominis plane (TAP) block in a randomized, controlled,
      double-blinded trial. The primary outcome was the morphine equivalents dose used
      in the first 24 h post-surgery. Secondary outcomes were pain scores and side
      effects, including pruritus, sedation, nausea and vomiting. METHODS: Planned
      recruitment was for 90 women; however, the study was terminated early. Sixty-nine
      women undergoing elective cesarean delivery under spinal anesthesia were
      enrolled. They were randomized to receive either intrathecal morphine 100 MUg
      plus a sham TAP block or a TAP block with 0.5% ropivacaine 1.5 mg/kg, to each
      side to a maximum of 20 mL. Women were assessed at 2, 6, 10, 24 h and 3 months
      post-spinal. RESULTS: Sixty-six women completed the trial. The morphine
      equivalents dose used in the TAP block group was greater at 24 h compared with
      the intrathecal morphine group (7.5 mg (95% CI 4.8-10.2) vs. 2.7 mg (95% CI 1.0
      4.3), F [1, 64]=9.62, P=0.003). There was no difference at 2, 6, or 10 h. Pain
      scores on rest and movement were higher in the TAP block group at all times
      although this only reached statistical significance at 10 h (P=0.001). Nausea and
      vomiting (P=0.02) and pruritus (P=0.007) were lower in the TAP block group.
      CONCLUSIONS: In this trial, the TAP block was associated with greater
      supplemental morphine requirements and higher pain scores than intrathecal
      morphine but fewer opioid-related side effects. The TAP block may be a reasonable
      alternative when intrathecal morphine is contraindicated or not appropriate.

PMID- 22410589
TI  - The relationships of positive and negative symptoms with neuropsychological
      functioning and their ability to predict verbal memory in psychotic major
      depression.
AB  - Neuropsychological functioning, in relation to positive and negative symptoms in
      psychotic major depression (PMD), has not been as thoroughly studied as it has
      been in schizophrenia. Thus, the current study investigated the associations
      between positive and negative symptoms with cognitive functioning, with an
      emphasis on verbal memory in PMD. Attention, working memory, and the executive
      functioning domains were analyzed among 49 PMD participants. Positive symptoms
      did not correlate significantly with any measures of verbal memory but did
      correlate with one measure of attention, working memory, and executive
      functioning. Negative symptoms correlated significantly with two California
      Verbal Learning Test-II (CVLT-II) measures of verbal memory and three measures of
      executive function. Hierarchical regressions were conducted to determine if
      negative symptoms could predict verbal memory performance after controlling for
      depression. Of the two verbal memory measures, negative symptoms significantly
      explained additional variance for CVLT Recognition, but not for CVLT Trials 1-5
      total score. Our results provide some evidence that, consistent with the
      schizophrenia literature, negative symptoms contributed more to verbal memory
      deficits in PMD than positive symptoms, regardless of depression severity.

PMID- 22410588
TI  - Purging behavior in anorexia nervosa and eating disorder not otherwise specified:
      a retrospective cohort study.
AB  - Purging behavior in eating disorders is associated with medical risks. We aimed
      to compare remission rates in purging and non-purging females with anorexia
      nervosa (AN) and eating disorder not otherwise specified (EDNOS) in a large
      retrospective single center cohort. A total of 339 patients with AN and 266
      patients with EDNOS were included in the study. The proportion of subjects with
      purging behavior at least once a week during the last 3 months was similar in the
      two groups: 22% in AN and 24% in EDNOS. Remission was defined by a goal weight
      >=85% of ideal body weight and no reported purging behavior in the last 6 months.
      The median time from onset to remission for patients with AN was 7 years for the
      non-purging vs. 11 years for the purging patients. The purging AN patients with
      both vomiting and laxative abuse displayed the poorest course. Among EDNOS
      patients, the time to remission was also significantly longer for purging
      patients compared to non-purging patients. Thus, in line with previous studies,
      we found that purging behavior is associated with delayed time to remission in
      treatment-seeking AN and EDNOS patients. This study provides evidence to support
      the retention of the diagnostic sub-typing in AN.

PMID- 22410590
TI  - Propofol interacts with stimulus intensities of electroconvulsive shock to
      regulate behavior and hippocampal BDNF in a rat model of depression.
AB  - As a psychiatric treatment, modern electroconvulsive therapy (ECT) requires
      anesthesia to enhance safety, but anesthetics may weaken its efficacy. Previous
      studies have provided inconsistent results and lack satisfactory details of the
      influence of anesthetics on ECT efficacy, which partially complicates the
      clinical selection of ECT protocols. To test our hypothesis that anesthetics
      interact with the intrinsic parameters of ECT to differentially regulate its
      therapeutic efficacy, we investigated the effects of the anesthetic propofol and
      the stimulus intensities of ECT on behavior and hippocampal brain-derived
      neurotrophic factor (BDNF) in a rodent model of depression. After treatment with
      chronic unpredictable mild stresses to produce the model, the depressed rats
      received anesthesia with propofol or normal saline, i.p., and electroconvulsive
      shock (ECS, an analog of ECT to animals) with different stimulus intensities. The
      sucrose preference and open field tests were performed to assess behavior, and
      BDNF level in hippocampus was measured with ELISA. We found that propofol
      regulated the efficacy of ECS differently at different stimulus intensities in
      both the behavioral and molecular levels. At medium intensities (120 and 180 mC),
      propofol enhanced the anti-depressant efficacy of ECS without largely
      compromising the recovering efficacy of ECS on spontaneous exploratory
      activities. The results indicated that propofol and ECS stimulus intensities
      interacted and resulted in different regulating efficacies at different
      intensities. Medium stimulus intensities were optimal for ECS efficacy under
      propofol anesthesia.

PMID- 22410591
TI  - Interpersonal psychosocial factors associated with underreported dietary energy
      intake in hemodialysis patients.
AB  - OBJECTIVE: To examine the association between degree of underreporting energy
      intake and psychosocial (including interpersonal and personal) factors among
      hemodialysis patients in Japan. DESIGN: We conducted a cross-sectional study.
      Predictors of difference were identified using multiple linear regression
      analysis. SETTING: Study was conducted at a public hospital and a dialysis clinic
      in a single district in northeast Honshu, Japan. SUBJECTS: Participants were
      hemodialysis outpatients. Patients aged more than 20 years and undergoing
      treatment for end-stage renal disease for at least 6 months were included.
      Exclusion criteria were diagnosis of depression, a mental disease, or dementia.
      MAIN OUTCOME: The outcome measure was the difference in reported energy intake
      defined by the differences between a brief administered dietary history
      questionnaire and diet record stratified by standardized weight. RESULTS: Seventy
      patients undergoing hemodialysis participated (44 men [62.9%] and 26 women
      [37.1%]). Of these, 54.3% underreported energy intake (by >10%). Sex (male) and
      employment status (employed) were statistically associated with energy intake
      underreporting. A lower score of dialysis staff encouragement was associated with
      greater energy intake underreporting (beta coefficient = 3.89 kcal/standardized
      weight, 95% confidence interval: 0.89 to 6.90; P = .012). CONCLUSION: Degree of
      underreporting energy intake is significantly associated with interpersonal
      psychosocial factors among hemodialysis patients in Japan. The interpersonal
      relationship with encouragement by the dialysis staff is important in improving
      the accuracy of reporting energy intake among dialysis patients.

PMID- 22410592
TI  - Vibration testing: a pilot study investigating the intra-tester reliability of
      the Vibrameter for the Median and Ulnar nerves.
AB  - The measurement of vibration thresholds (VTs) is a sensitive test for identifying
      and monitoring neuropathies. Such a test needs established reliability. The
      purpose of this research was to evaluate the intra-tester reliability of VT
      measurements of the Median and Ulnar nerves in asymptomatic participants. A
      double blinded repeated measures study was carried out. The VTs of the Median and
      Ulnar nerves were measured on two occasions with seven days between measurements.
      Participants were trained in identifying the sensation before commencing
      measurement. 22 participants who fulfilled the inclusion criteria were recruited.
      Intra-rater reliability was analysed used the intra-class correlation. The median
      nerve showed excellent reliability (ICC = .922; standard error of the mean =
      .0225 MUm; 'true' SEM = .045 MUm; smallest real difference = .062 MUm). Ulnar
      nerve reliability was 'substantial' (ICC = .632; standard error of the mean =
      .0225 MUm; 'true' SEM = .055 MUm; smallest real difference = .085 MUm). The VT
      measurements showed excellent to substantial reliability. The Vibrameter has the
      potential for excellent reliability providing manual therapists practice the
      technique of using it. It could usefully be considered by manual therapists to
      support their practice.

PMID- 22410593
TI  - Methods of studying telomere damage induced by quadruplex-ligand complexes.
AB  - The burgeoning knowledge about the structure of telomeres and the roles of
      various factors involved in telomere maintenance provides several possible
      targets for pharmacological intervention. To date the area that has received
      major attention regarding drug discovery is the targeting the telomeric G
      quadruplex (G4) structure. G4 ligands were initially designed to counteract
      telomerase action at telomeres. Surprisingly, their antiproliferative effects can
      occur in telomerase negative cells and follow kinetics, which cannot be merely
      explained by telomere shortening, suggesting that these compounds affect other
      pathways, not necessarily related to telomere biology. Impressively, it has been
      shown that polyaromatic compounds featuring end-stacking binding properties
      trigger a strong DNA damage response at telomeres. This is typical of the
      telomere deprotection occurring during cellular senescence or upon telomere
      injury. It emerged that the G4-interacting agents are more than simple telomerase
      inhibitors and that their direct target is rather telomere than telomerase. This
      review summarizes the most valid experimental approaches for studying the
      pharmacological telomere damage induced by G4-ligand complexes.

PMID- 22410594
TI  - Emergency medicine and hospital medicine: a call for collaboration.
AB  - BACKGROUND: In the United States, emergency physicians and hospitalists are
      increasingly responsible for managing hospitalized patients. These specialists
      share a common practice space and similar shift work schedules. Together they
      govern decisions about use of the most expensive care setting in medicine--the
      hospital. DISCUSSION: Unfortunately, in most institutions there is little
      collaboration between emergency physicians and hospitalists, resulting in missed
      opportunities to improve the quality of care and reduce its cost. In this call to
      action, we challenge emergency physicians and hospitalists to work together to
      develop protocols for consistent, evidence-based, and expeditious care of
      patients admitted from the ED; to collaborate in the care of ED patients who can
      safely be discharged home; to pursue joint quality, hospital leadership, and cost
      effectiveness projects; to work in partnership to assure adequate staffing of
      hospital-based specialists; and to cooperate in the professional, front-line
      assessment of clinically and fiscally driven policies aimed at assessing the
      appropriateness of hospital admissions and readmissions. SUMMARY: Hospital care
      is increasingly driven by emergency physicians and hospitalists. We envision a
      vital role for ongoing collaboration between them in achieving the goals of
      patient care, education, and quality and safety outcomes.

PMID- 22410595
TI  - Pneumatosis intestinalis and ulcerative colitis.

PMID- 22410596
TI  - [The protective factors of suicide probability in religious male high school
      students].
AB  - PURPOSE: This study was conducted to identify the protective factors that
      influence suicide probability in religious male high school students. METHODS:
      The data was collected from Nov. 5 to Dec. 10, 2009. Data were collected by self
      report questionnaire from 255 students selected from 2 religious male high
      schools in B city. The instruments for this study were the Suicide Probability
      Scale for Adolescence (SPS-A), Inventory Parents Peer Attachment-Revision (IPPA
      R), Spiritual Well-being Scale (SWBS), and Ego-identity Scale. The data were
      analyzed using t-test, one-way ANOVA, Scheffe test, Pearson correlation
      coefficients and stepwise multiple regression with the SPSS 14.0 program.
      RESULTS: The protective factors of suicide probability in religious male high
      school students were identified as existential spiritual well-being (beta= -.46,
      p<.001), self-identity (beta= -.30, p<.001), and mother attachment (beta= -.21,
      p<.001). These three factors explained 61.5% of the variance in suicide
      probability. CONCLUSIONS: The results suggest that improvement in spirituality,
      ego-identity, and mother attachment for religious male high school students is
      important to reduce the probability of suicide.

PMID- 22410597
TI  - [A model on turnover intention of chief nurse officers].
AB  - PURPOSE: The purpose of this study was to test the turnover intention model for
      chief nurse officers in general hospitals. The variables for the study included
      job stress, social support, job satisfaction, and organization commitment.
      METHODS: A predictive, non-experimental design was used with a sample of 144
      chief nurse officers from 144 general hospitals. Data were collected using self
      administered questionnaires and analyzed using SPSS, AMOS program. RESULTS: The
      overall fitness of the hypothetical model to the data was good (chi2=16.80,
      p=.052, GFI=.96, AGFI=.90, NFI=.97, CFI=.99). Job stress, social support, job
      satisfaction, and organization commitment explained 59.0% of the variance in
      turnover intention by chief nurse officers. Both organization commitment and
      social support directly influenced turnover intention for chief nurse officers,
      and job stress and job satisfaction indirectly influenced turnover intention.
      CONCLUSION: The results imply that chief nurse officers in hospitals need social
      support and management of job stress to increase job satisfaction and
      organization commitment, and lower turnover intention.

PMID- 22410598
TI  - [Effectiveness of a motivational interviewing smoking cessation program on
      cessation change in adolescents].
AB  - PURPOSE: This study examined the effectiveness of an Adolescent Motivational
      Interviewing Cessation program on smoking cessation change. The study was done
      with a nonequivalent control group pretest-posttest design. METHODS: The
      participants were 39 high school students from G city, who were in school from
      September 1 to October 30, 2009. The students were assigned to the experimental
      group (20) and participated in the motivational interviewing cessation program or
      to the control group (19) who did not participate. Data analyses involved chi2
      test, independent t-test, Repeated Measures ANOVA, and utilized the SPSS program.
      RESULTS: The experimental group had significantly less daily smoking, nicotine
      dependence and smoking temptation in comparison to the control group. The
      experimental group had significantly higher stage of change in comparison to the
      control group. CONCLUSION: The results of the study indicate that a motivational
      interviewing cessation program delivered to adolescents who smoke is an effective
      method of encouraging cessation, and can be utilized as an effective nursing
      intervention for adolescents who smoke.

PMID- 22410599
TI  - [Effects of a short-term life review on spiritual well-being, depression, and
      anxiety in terminally ill cancer patients].
AB  - PURPOSE: This study was done to evaluate the effects of a short-term life review
      on spiritual well-being, depression, and anxiety in patients with terminal
      cancer. METHODS: The study used a pre posttest quasi experimental design with a
      nonequivalent control group. Measurement instruments included the Functional
      Assessment of Chronic Illness Therapy-Spiritual scale (FACIT-Sp12) and the
      Hospital Anxiety and Depression Scale (HADS). Participants were 32 patients with
      terminal cancer who were receiving chemotherapy or palliative care at hospitals
      or at home. Eighteen patients were assigned to the experimental group and 14 to
      the control group. A sixty minute short-term life review session was held twice a
      week as the intervention with the experimental group. RESULTS: There was a
      statistically significant increase in spiritual well-being in the experimental
      group compared to the control group. There were also significant decreases in
      depression and anxiety in the experimental group compared to the control group.
      CONCLUSION: The results indicate that a short-term life review can be used as a
      nursing intervention for enhancing the spiritual well-being of patients with
      terminal cancer.

PMID- 22410600
TI  - [Adaptation experience to family of immigrant women in multicultural families].
AB  - PURPOSE: This study was to explore adaptation experience to family among women
      who immigrated for marriage. Specific aims were to identify problems immigrant
      women face as family members and how they interact with other family members.
      METHODS: Grounded theory methodology was utilized. Data were collected from
      iterative fieldwork with individual in-depth interviews from 6 immigrant women as
      key informants, and 2 of their husbands and 2 of their mothers-in-law as general
      informants. RESULTS: Through constant comparative analysis, a core category
      emerged as "tearing down the wall in communicating". Causal conditions were
      feeling frustrated in one's expectations, differences in language and life style,
      differences in recognition, and perceptions of discrimination and prejudice.
      Strategies were learning the Korean language, learning Korean culture, managing
      stress, mediating differences between family members, and introspecting.
      Intervening factors were support systems, burdens of child-rearing, and the
      condition of one's health. Consequences were rooting oneself in one's family and
      accepting one's life as it is. CONCLUSION: Results of the study indicate that
      there is a need for nurses to understand differences in communication with family
      members among immigrant women and to provide information and emotional support to
      improve the adaptation of these women to their Korean families.

PMID- 22410601
TI  - [Statistical methods to control response bias in nursing activity surveys].
AB  - PURPOSE: The aim of this study was to compare statistical methods to control
      response bias in nursing activity surveys. METHODS: Data were collected at a
      medical unit of a general hospital. The number of nursing activities and consumed
      activity time were measured using self-report questionnaires. Descriptive
      statistics were used to identify general characteristics of the units. Average, Z
      standardization, gamma regression, finite mixture model, and stochastic frontier
      model were adopted to estimate true activity time controlling for response bias.
      RESULTS: The nursing activity time data were highly skewed and had non-normal
      distributions. Among the 4 different methods, only gamma regression and
      stochastic frontier model controlled response bias effectively and the estimated
      total nursing activity time did not exceeded total work time. However, in gamma
      regression, estimated total nursing activity time was too small to use in real
      clinical settings. Thus stochastic frontier model was the most appropriate method
      to control response bias when compared with the other methods. CONCLUSION:
      According to these results, we recommend the use of a stochastic frontier model
      to estimate true nursing activity time when using self-report surveys.

PMID- 22410602
TI  - [Effects of cognitive behavioral therapy program on mental health problems in
      children dealing with trauma: focused on community district victimized by oil
      spill].
AB  - PURPOSE: This study was done to evaluate the effects of cognitive behavioral
      therapy in a victimized community district and to determine if the program is an
      effective nursing intervention to reduce posttraumatic stress disorder symptom,
      depression and state anxiety. METHODS: A nonequivalent control group design was
      used for the study. The participants, 32 elementary school students, were
      selected from grades 4, 5, 6 and each student was assigned to either the
      experimental (16) or control (16) group. Cognitive behavioral therapy was used as
      the experimental treatment from April 9 to May 28, 2009. The experimental group
      received cognitive behavior therapy intervention 8 times. Data analysis was done
      using ANCOVA with SPSS 17.0. RESULTS: After the intervention, the experimental
      group showed significantly lower levels of posttraumatic stress disorder symptoms
      than the control group. CONCLUSION: The findings from this study suggest that
      cognitive behavioral therapy is an effective nursing intervention to decrease the
      level of mental health problems of children in victimized district. Further
      research is required in order to identify the continuous effects of cognitive
      behavioral therapy.

PMID- 22410603
TI  - [Violent experiences and coping among home visiting health care workers in
      Korea].
AB  - PURPOSE: The purpose of this study was to explore violent experiences of home
      visiting health care workers in Korea. METHODS: This study was a cross-sectional
      survey. Data were collected using self-report questionnaires from 1,640 health
      care workers. Data collection was done between September 1, 2009 and June 30,
      2010. RESULTS: Of the respondents, 70.6% had experienced work-related violence.
      Shouting (51.9%) was the most common verbal violence, followed by verbalizing
      sexual remarks to the health care workers (19.0%) and touching the hands (16.5%),
      the most common acts relating to sexual harassment. Of the respondents who had
      experienced violence, 50.9% told their peers about the incidents. However, the
      major reasons why they did not report these incidents was due to the fact that
      they felt it was useless to file reports and that they expected such incidents to
      occur as part of their job. The majority of the respondents (86.4%) wanted
      education on how to deal with such violence at work. CONCLUSION: The results of
      this study indicate that efforts should be made to increase awareness and to
      minimize violence in the workplace. Also, educational programs should be designed
      to improve knowledge and to prevent workplace violence.

PMID- 22410604
TI  - [Validation of a Korean translated version of the Critical Care Pain Observation
      Tool (CPOT) for ICU patients].
AB  - PURPOSE: The purpose of this methodological study was to examine the reliability
      and validity of a translated Korean version of the Critical Care Pain Observation
      Tool (CPOT) developed for assessment of pain in critically ill nonverbal
      patients. METHODS: A cross-sectional study design was used. Data were collected
      from a convenience sample of 202 critically ill patients admitted to a university
      hospital. Upon establishment of content and translation equivalence between the
      English and Korean version of CPOT, psychometric properties were evaluated.
      RESULTS: The interrater reliability was found to be acceptable with the weighted
      kappa coefficients of .81-.88. Significant high correlations between the CPOT and
      the Checklist of Nonverbal Pain Indicators were found indicating good concurrent
      validity (r=.72-.83, p<.001). Data showed the area under the ROC curve of 0.86
      with a cut-off point of 1, which resulted in 76.9% sensitivity and 88.6%
      specificity. The mean score of CPOT during suctioning was significantly different
      from that of before (t=-14.16, p<.001) or 20 minutes after suctioning (t=16.31,
      p<.001). CONCLUSION: Results of this study suggest that the CPOT can be used as a
      reliable and valid measure to assess pain in critically ill nonverbal patients.

PMID- 22410605
TI  - [Effects of nurses' perception of servant leadership on leader effectiveness,
      satisfaction and additional effort: focused on the mediating effects of leader
      trust and value congruence].
AB  - PURPOSE: This study was done to examine the effects of nurses' perception of
      servant leadership on leader effectiveness, satisfaction and promoting additional
      effort. The focus was the mediating effects of leader trust and value congruence.
      METHODS: Data were collected from 361 RN-BSN students and nurses participating in
      nationally attended in-service training programs. Data were analyzed using
      descriptive statistics and structural analysis with SPSS 17.0 windows program and
      Amos 7.0. RESULTS: Direct effects of nurses' perception of servant leadership
      were negative, but mediating effects of trust and value congruency were
      positively correlated with leader effectiveness, satisfaction and additional
      effort, that is servant leadership should be effective through mediating factors.
      CONCLUSION: The study results indicate that if the middle managers of nurses can
      build leader trust and value congruency between nurses through servant
      leadership, leader effectiveness, satisfaction and additional effort on the part
      of the nurses could result in a positive change in the long term.

PMID- 22410606
TI  - [Effects of a home-based exercise program for patients with stomach cancer
      receiving oral chemotherapy after surgery].
AB  - PURPOSE: The purpose of this study was to identify the effects of a home based
      exercise program for patients with stomach cancer who were undergoing oral
      chemotherapy. METHODS: The home-based exercise program was developed from the
      study findings of Winningham (1990) and data from the Korea Athletic Promotion
      Association (2007). The home-based exercise program consisted of 8 weeks of
      individual exercise education and exercise adherence strategy. Participants were
      24 patients with stomach cancer who were undergoing oral chemotherapy following
      surgery in 2007 or 2008 at a university hospital in Seoul. Patients were randomly
      assigned to either the experimental group (11) or control group (13). The effects
      of the home-based exercise program were measured by level of cancer related
      fatigue, NK cell ratio, anxiety, and quality of life. Data were analyzed using
      SPSS/WIN 13.0 version. RESULTS: The degree of cancer related fatigue and anxiety
      in the experimental group decreased compared to the control group. The NK cell
      ratio and the degree of quality of life of experimental group increased while
      that of the control group decreased. CONCLUSION: This study result indicate the
      importance of exercise and provide empirical evidence for continuation of safe
      exercise for patients with cancer during their chemotherapy.

PMID- 22410607
TI  - [A structural model for psychosocial adjustment in patients with early breast
      cancer].
AB  - PURPOSE: This study was done to propose a structural model to explain and predict
      psychosocial adjustment in patients with early breast cancer and to test the
      model. The model was based on the Stress-Coping Model of Lazarus and Folkman
      (1984). METHODS: Data were collected from February 18 to March 18, 2009. For data
      analysis, 198 data sets were analyzed using SPSS/WIN12 and AMOS 7.0 version.
      RESULTS: Social support, uncertainty, symptom experience, and coping had
      statistically significant direct, indirect and total effects on psychosocial
      adjustment, and optimism had significant indirect and total effects on
      psychosocial adjustment. These variables explained 57% of total variance of the
      psychosocial adjustment in patients with early breast cancer. CONCLUSION: The
      results of the study indicate a need to enhance psychosocial adjustment of
      patients with early breast cancer by providing detailed structured information
      and various symptom alleviation programs to reduce perceived stresses such as
      uncertainty and symptom experience. They also suggest the need to establish
      support systems through participation of medical personnel and families in such
      programs, and to apply interventions strengthening coping methods to give the
      patients positive and optimistic beliefs.

PMID- 22410608
TI  - [Effects of rotated endotracheal tube fixation method on unplanned extubation,
      oral mucosa and facial skin integrity in ICU patients].
AB  - PURPOSE: The study was done to compare effects of two endotracheal tube (ET tube)
      fixation methods (rotated fixation versus conventional) on unplanned extubation
      and skin integrity for orally intubated patients in intensive care units.
      METHODS: The research design was a non-equivalent control group with repeated
      measures design. Participants were 80 patients; 40 participants assigned to each
      group. ET tube for the experimental participants fixed with rotated method every
      morning. Unplanned extubation was assessed by bedside nurses using the unplanned
      extubation report form. Oral mucosa and facial skin integrity were assessed using
      oral assessment guide and facial skin integrity assessment guide at day 3, 7, 10
      and 14. RESULTS: There was no difference in the unplanned extubation rate between
      the two groups. Oral mucosa impairment scores for the rotated fixation method
      were significantly lower at day 7 (p=.044), 10 (p=.048) and day 14 (p=.037). Also
      facial skin integrity impairment scores for the same group were significantly
      lower at day 7 (p=.010), 10 (p=.003), and 14 (p=.002). CONCLUSION: Results of the
      study suggest that the rotated fixation method is effective for these patients,
      to prevent impairment of oral mucosa and facial skin integrity. Further research
      is needed to prevent unplanned extubation.

PMID- 22410609
TI  - [Effects of an elder health promotion program using the strategy of elder health
      leader training in senior citizen halls].
AB  - PURPOSE: This study was conducted to develop and test the effects of an elder
      health promotion program and apply strategies for elder health leader training
      sessions with elders at senior citizen halls. METHODS: A nonequivalent control
      group pretest-posttest design was used. Participants were 49 elders at a senior
      citizen hall (intervention: 27, control: 22). The elder health promotion program
      consisted of health education and exercise. A professional leader led the program
      for 4 weeks, and then an elder health leader and research assistant led for 8
      weeks (total 12 weeks). Scales for elder health promoting behaviors, perceived
      health status, life satisfaction and senior citizen hall capability were used and
      physical fitness levels were measured. Data were collected between April 21 and
      July 28, 2010 and analyzed using Chi-square, Fisher's exact test, t-test, and
      repeated measure ANOVA with SPSS/WIN 12.0. RESULTS: Health promoting behaviors,
      physical fitness, perceived health status, and senior citizen hall capacity were
      significantly better in the experimental group after the intervention compared to
      the control group. CONCLUSION: Study findings indicate that elder health
      promotion programs applying strategies of elder health leader training are
      effective and can be recommended as nursing interventions for health promotion of
      these elders.

PMID- 22410610
TI  - [Gender difference in risk factors for depression in community-dwelling elders].
AB  - PURPOSE: This study was conducted to compare the degree of depression between men
      and women and to identify factors influencing their depression. METHODS:
      Participants in this cross-sectional descriptive study were 263 persons over 65
      years old (men: 103, women: 160). Data were collected through face to face
      interviews using questionnaires and were done in two urban areas in 2010.
      Research instruments utilized in this study were SGDS, MMSE-K, SRH, FILE, sleep
      pattern scale, family and friend support scale, and social support scale.
      Multivariate regression analysis was performed to identify factors influencing
      depression in elders. RESULTS: The proportions of participants with depression
      were significantly different between men and women (52.4% vs. 67.5%). Regression
      model for depression in elderly men significantly accounted for 54%; disease
      stress (32%), economic stress (10%), perceived health status (4%), and family
      support, educational level, age, and hypertension. Regression model for
      depression in elderly women significantly accounted for 47%; disease stress
      (25%), perceived social loneliness (8%), friend support (5%), family stress (4%),
      and sleep satisfaction, and family support. CONCLUSION: Results demonstrate that
      depression is an important health problem for elders, and show gender differences
      for factors influencing depression. These results could be used in the developing
      depression prevention programs.

PMID- 22410611
TI  - Interaction of human cytochrome P4503A4 with ritonavir analogs.
AB  - Ritonavir is a HIV protease inhibitor that also potently inactivates cytochrome
      P450 3A4 (CYP3A4), a major human drug-metabolizing enzyme. To better understand
      the mechanism of ligand binding and to find strategies for improvement of the
      inhibitory potency of ritonavir, currently administered to enhance
      pharmacokinetics of other anti-HIV drugs that are quickly metabolized by CYP3A4,
      we compared the manner of CYP3A4 interaction with the drug and two analogs
      lacking either the heme-ligating thiazole nitrogen or the entire thiazole group.
      Based on the kinetic, mutagenesis and structural data, we conclude that: (i) the
      active site residue Arg212 assists binding of all investigated compounds and,
      thus, may play a more prominent role in metabolic transformation of xenobiotics
      than previously thought, (ii) peripheral binding of ritonavir limits the heme
      coordination rate and complicates the binding kinetics, (iii) association of
      ritonavir-like type II ligands is driven by heme coordination whereas hydrophobic
      forces define the binding mode, and (iv) substitution of one phenyl group in
      ritonavir with a smaller hydrophobic moiety could prevent steric clashing and,
      hence, increase the affinity and inhibitory potency of the drug.

PMID- 22410612
TI  - Simple and robust in vivo and in vitro approach for studying virus assembly.
AB  - In viruses with positive-sense RNA genomes pathogenic to humans, animals and
      plants, progeny encapsidation into mature and stable virions is a cardinal phase
      during establishment of infection in a given host. Consequently, study of
      encapsidation deciphers the information regarding the know-how of the mechanism
      regulating virus assembly to form infectious virions. Such information is vital
      in formulating novel methods of curbing virus spread and disease control. Virus
      encapsidation can be studied in vivo and in vitro. Genome encapsidation in vivo
      is a highly regulated selective process involving macromolecular interactions and
      subcellular compartmentalization. Therefore, study leading to dissect events
      encompassing virus encapsidation in vivo would provide basic knowledge to
      understand how viruses proliferate and assemble. Recently in vitro encapsidation
      has been exploited for the research in the area of biomedical imaging and
      therapeutic applications. Non-enveloped plant viruses stand far ahead in the
      venture of in vitro encapsidation of the negatively charged foreign material.
      Brome mosaic virus (BMV), a non-enveloped multicomponent RNA virus pathogenic to
      plants, has been used as a model system for studying genome packaging in vivo and
      in vitro. For encapsidation assays in Nicotiana benthamiana plants, Agrobacterium
      -mediated transient expression, refer to as agroinfiltration, is an efficient and
      robust technique for the synchronized delivery and expression of multiple
      components to the same cell. In this approach, a suspension of Agrobacterium
      tumefaciens cells carrying binary plasmid vectors carrying cDNAs of desiredviral
      mRNAs is infiltrated into the intercellular space withina leaf using nothing more
      sophisticated than a 1 ml disposable syringe (without needle). This process
      results in the transfer of DNA insert into plant cells; the T-DNA insert remains
      transiently in the nucleus and is then transcribed by the host polymerase II,
      leading to the transient expression. The resulting mRNA transcript (capped and
      polyadenylated) is then exported to the cytoplasm for translation. After
      approximately 24 to 48 hours of incubation,sections of infiltrated leaves can be
      sampled for microscopyor biochemical analyses. Agroinfiltration permits large
      numbers (hundreds to thousands) of cells to be transfected simultaneously. For in
      vitro encapsidation, purified virions of BMV are dissociated into capsid protein
      by dialyzing against dissociation buffer containing calcium chloride followed by
      removal of RNA and un-dissociated virions by centrifugation. Genome depleted
      capsid protein subunits are then reassembled with desired viral genome components
      or non-viral components such as indocyanine dye.

PMID- 22410613
TI  - Intracameral and topical voriconazole for fungal corneal endoexudates.
AB  - PURPOSE: To evaluate the role of intracameral and topical voriconazole as
      treatment for fungal keratitis presenting with endothelial exudates. METHODS:
      Five eyes of 5 patients with fungal keratitis presenting with endoexudates with
      or without infiltrates in the corneal stroma were included in the study.
      Intracameral voriconazole 50 mcg/0.1 mL was given followed by topical
      voriconazole 1% hourly. Main outcome measure was Resolution of endoexudates and
      corneal stromal infiltrates. RESULTS: On presentation, all 5 eyes had
      endoexudates. Diagnosis of fungal keratitis was based on microbiological analysis
      of endoexudates (3 eyes) and corneal scrapings (2 eyes). After the intervention,
      the reduction in the size and density of endoexudates were documented and a
      complete resolution of the infection was seen in all cases within 3 weeks to 3
      months. Two patients experienced burning sensations with topical voriconazole.
      Best-corrected visual acuity (BCVA) at presentation was hand motions in 3
      patients and less than 20/125 in the remaining 2 patients. Final BCVA varied from
      20/2000 to 20/40 depending on location of corneal scar. CONCLUSION: Intracameral
      and topical voriconazole may be effective against deep fungal keratitis
      presenting with endoexudates.

PMID- 22410614
TI  - Impact of eye bank lamellar tissue cutting for endothelial keratoplasty on
      bacterial and fungal corneoscleral donor rim cultures after corneal
      transplantation.
AB  - PURPOSE: To determine if the lamellar cut of donor tissue for endothelial
      keratoplasty (EK) by an eye bank facility is associated with a change in the
      prevalence of positive bacterial or fungal donor rim cultures after corneal
      transplantation. METHODS: A retrospective review was conducted of bacterial and
      fungal cultures of donor rims used for corneal transplantation at a tertiary eye
      care center from January 1, 2003, to December 31, 2008, with tissue provided by a
      single eye bank. The cases were divided into 2 groups. Group 1 ("no-cut")
      included keratoplasty procedures in which a lamellar cut was not performed. Group
      2 ("precut") included EK procedures in which a 4-hour period of prewarming of
      tissue followed by a lamellar cut was performed in the eye bank before tissue
      delivery to the operating surgeon. RESULTS: There were 351 donor rim cultures in
      group 1 and 278 in group 2. Bacterial cultures were positive in 30 donor rims
      (8.5%) in group 1 and 13 (4.7%) in group 2 (P = 0.058). Positive bacterial
      cultures were not associated with any postoperative infections. Fungal cultures
      were positive in 8 donor rims (2.3%) in group 1 and 7 (2.5%) in group 2 (P =
      1.0). Positive fungal cultures were associated with 2 cases (13.3%) of
      postoperative fungal infections. CONCLUSIONS: Corneal donor tissue can be precut
      for EK by trained eye bank personnel without an increased risk of bacterial or
      fungal contamination.

PMID- 22410615
TI  - Elevation changes of central posterior corneal surface after intracorneal ring
      segment implantation in keratoconus.
AB  - PURPOSE: To compare changes that occur at the posterior corneal surface after the
      implantation of intracorneal ring segments (ICRSs) using either mechanical or
      femtosecond laser-assisted procedures and to correlate these changes with the
      visual outcome achieved. METHODS: Retrospective, nonrandomized, and
      interventional case series including 223 consecutive eyes of 186 patients with
      keratoconus ranging in age from 16 to 39 years that were implanted with ring
      segments (KeraRing; Mediphacos) at Kartal Training and Research Hospital,
      Istanbul, Turkey. Two groups were created according to the surgical technique
      used: mechanical group (168 eyes) and femtosecond group (55 eyes). Visual and
      refractive outcomes and corneal elevation changes were evaluated during a 24
      month follow-up. Correlations between visual and posterior elevation changes were
      evaluated. RESULTS: The posterior corneal surface could not be analyzed with
      accuracy for diameters larger than the diameter of the ICRS implant. A
      statistically significant reduction of maximum elevation for both the corneal
      surfaces was observed at 1 month after the surgery (P < 0.01), with additional
      reductions at 3 and 6 months (P <= 0.03). In addition, the posterior best-fit
      sphere was flattened significantly at 1 month after the surgery in both the
      groups, with additional flattening at 3 months (P <= 0.03). No significant
      differences between groups in posterior corneal elevation parameters were found
      at any time point of the follow-up (P >= 0.14). Moderate and significant
      correlations of the postoperative visual outcome with the change in posterior
      best-fit sphere were found only in the femtosecond group. CONCLUSIONS: A central
      corneal flattening of the posterior corneal surface occurs after ring segment
      implantation in keratoconus.

PMID- 22410616
TI  - A quasi-2-dimensional model for respiration of the cornea with soft contact lens
      wear.
AB  - PURPOSE: Because neither the human cornea nor a soft contact lens (SCL) is of
      constant thickness, corneal oxygenation varies locally. To quantify the
      importance of cornea/SCL thickness variations on oxygen demand, we develop a
      quasi-2-dimensional (2D) respiration model that accounts for aerobic and
      anaerobic metabolism and bicarbonate buffering. METHODS: Because metabolism is
      critical to oxygen demand, we extend the 1-dimensional (1D), 6-layer oxygen
      metabolic model of Chhabra et al. Lateral diffusion is shown to be negligible.
      Accordingly, we adopt the 1D reactive-diffusion metabolic model but apply it
      locally along the cornea/lens extent. This "quasi-2D" approximation permits 2D
      assessment of oxygen consumption, including the effects of carbon dioxide,
      glucose, and lactate, bicarbonate, and hydrogen ions. We use both an oxygen
      deficiency factor and an excess lactate factor to gauge corneal health after
      accounting for both cornea and contact lens thickness variations. RESULTS: The
      quasi-2D respiration model provides quantitative spatial resolution of corneal
      oxygenation with minimal expenditure of computation time. When only aerobic
      oxygen loss is included, our quasi-2D approach is in excellent agreement with the
      fully 2D results of Alvord et al. However, the quasi-2D model predicts 2D
      concentration profiles of glucose, lactate ions, bicarbonate ions, hydrogen ions,
      and carbon dioxide, as well as oxygen. Neglect of metabolic reactions and/or
      thickness variations leads to inaccurate prediction of oxygen demand, especially
      near the lens periphery. CONCLUSIONS: The quasi-2D respiration model indicates
      that lateral thickness variations and respiration kinetics are critical for
      assessing on-eye physiologic performance of an SCL. We find that oxygen
      deficiency factor and excess lactate factor are useful indices to gauge corneal
      hypoxia. A user-friendly computer program of the quasi-2D respiration model is
      available for lens design.

PMID- 22410617
TI  - Forgive and forget?

PMID- 22410618
TI  - Culturally competent care: are we there yet?

PMID- 22410619
TI  - Cephalosporin-resistant Shigella flexneri over 9 years (2001-09) in India.
AB  - OBJECTIVES: To determine the pattern and antimicrobial resistance genes of
      cephalosporin resistance in Shigella flexneri and Shigella dysenteriae over 9
      years. METHODS: Isolates of Shigella (S. flexneri, n = 119 and S. dysenteriae, n
      = 24) were tested for resistance to ceftriaxone and cefepime by disc diffusion,
      for MIC by Etest and for extended-spectrum beta-lactamase (ESBL) and AmpC
      production. The presence of antimicrobial resistance genes was investigated by
      PCR using specific primers for bla(TEM), bla(OXA-1), bla(CTX-M-15), bla(SHV) and
      bla(CMY-2) for all the isolates. RESULTS: Twenty (16.8%) S. flexneri isolates
      were resistant/intermediately susceptible to ceftriaxone/cefepime, while all S.
      dysenteriae were susceptible. In S. flexneri isolates, the MIC(50) values of
      ceftriaxone and cefepime were found to be 0.032 and 0.125 mg/L, respectively,
      while their MIC(90) values were 12 and 8 mg/L, respectively. The MIC(50) and
      MIC(90) for S. dysenteriae were below 1 mg/L for ceftriaxone; however, for
      cefepime the MIC(90) was found to be 4 mg/L. Of the 20 resistant/intermediately
      susceptible S. flexneri isolates, 9 were positive for ESBL production and 4 for
      AmpC production by phenotypic tests. All 20 isolates were found to be positive
      for bla(TEM), 10 for bla(CTX-M-15), 8 for bla(OXA) and 7 for bla(CMY-2); none was
      positive for bla(SHV). CONCLUSIONS: We report a high level of cephalosporin
      resistance with high MICs and ESBL- and AmpC-mediated antibiotic resistance in
      Shigella from north India.

PMID- 22410620
TI  - Impact of a 14-year screening programme on tuberculosis transmission among the
      homeless in Paris.
AB  - OBJECTIVE: To evaluate the impact of an active case-finding programme on
      tuberculosis (TB) transmission in homeless shelters in Paris, France. DESIGN:
      Between 1994 and 1997, an active case-finding programme was implemented in
      homeless shelters using a mobile radiological screening  unit, and continued from
      1997 to 2007. During these periods, the strains isolated from TB cases diagnosed
      in the homeless were genotyped by restriction fragment length polymorphism
      analysis using the insertion sequence IS6110 as a probe. RESULTS: Between 1994
      and 2007, 313 new TB  cases were diagnosed among the homeless population: 179
      through the programme among shelter users, and 134 among homeless people not
      using shelters. Half of the strains were clustered in 35 distinct patterns (2-48
      cases/cluster). The clustering of TB cases steadily decreased in shelters  during
      the 13 years of the survey, from 14.3 to 2.7 related cases per year (P < 0.01)
      and from 75% to 30% of related cases among all TB cases (P < 0.01). In contrast,
      there was only a slight trend towards a decrease in homeless people not using
      shelters. CONCLUSION: Active case finding in homeless shelters resulted in a
      decrease in case clustering, mainly in shelter users. Genotyping contributed to
      confirming the positive impact of the intervention.

PMID- 22410621
TI  - Source and risk assessment of PCBs in sediments of Fenhe reservoir and watershed,
      China.
AB  - The concentrations of polychlorinated biphenyls (PCBs) in sediments from the
      Fenhe reservoir and watershed were detected at 28 sites in wet and dry seasons.
      The ?(123)PCBs ranged from n.d. to 126.49 ng g(-1) dw. The dominated congeners
      were tri-PCBs (34.29%) and tetra-PCBs (24.05%). In the Fenhe reservoir,
      ?(123)PCBs presented a decreasing trend, while percentages of low chlorinated
      congeners showed an increasing trend. For the temporal variations, PCBs
      homologues profiles of sediment samples and spatial distribution of ?(123)PCBs
      for the two periods were similar (with CD = 0.021 and r(2) = 0.999 respectively),
      although PCBs concentrations in the wet season were significantly higher than in
      the dry season. PCA was applied to analyze the possible sources for PCBs,
      suggesting that PCBs might be mainly influenced by Aroclor 1016 and 1242.
      Compared with 3 established sediment quality guidelines, levels of PCBs in
      sediments of the investigated watershed might have a potential biological impact,
      especially in the wet season.

PMID- 22410622
TI  - Put DDT residues and human health in perspective.

PMID- 22410623
TI  - Transformation of tetrabromobisphenol A in the presence of different solvents and
      metals.
AB  - Solvent-based separation method is presumably an efficient and environmentally
      beneficial approach for elimination of brominated flame retardants (BFRs) from
      waste electrical and electronic equipment (WEEE). The overall goal of this study
      was to evaluate possible effects of organic solvent on the behavior of BFRs
      during solvent-based processing of WEEE. We initiated a set of batch experiments
      for examining the rates and possible pathways of transformation of a
      representative BFR (tetrabromobisphenol A, TBBPA) using acetone, toluene, and
      methanol as the solvents. Our results showed that toluene and methanol had no
      effect on the transformation of TBBPA, but approximately 20% of TBBPA (100 mg L(
      1)) was transformed by acetone within 2 h at 50 degrees C. Analysis of the
      products with GC-MS showed that two high-molecular-weight products (MW=586) were
      major products of the transformation reactions. The role of acetone as a reactant
      in the transformation of TBBPA was further validated with dueterated acetone. In
      addition, the effects of co-existing metals in WEEE (i.e., Zn, Cu, and Ni) on the
      transformation of TBBPA in the solvent systems were investigated. These metals
      tested were found to greatly enhance the rates of TBBPA transformation. The metal
      facilitated solvent reactions with TBBPA may lower the extractability of TBBPA by
      formation of larger and less soluble products, hence potentially increasing the
      cost for separating the chemical from WEEE.

PMID- 22410624
TI  - Effects of polychlorinated biphenyls on whole animal energy mobilization and
      hepatic cellular respiration in rainbow trout, Oncorhynchus mykiss.
AB  - The production of polychlorinated biphenyls (PCBs) was banned in 1977 but these
      chemicals persist in the environment and threaten aquatic organisms. PCB exposure
      often results in activation of the aryl hydrocarbon receptor (AhR) and increases
      in hepatic detoxification mechanisms. Activation of these detoxification
      mechanisms is believed to be associated with energetic demands that may come at
      the expense of other physiological processes such as growth, activity and
      reproduction. We tested the hypothesis that exposure to sub-lethal levels of PCBs
      results in increased energy demand and energy mobilization using both an in vivo
      and in vitro approach. Rainbow trout (Oncorhynchus mykiss) received a single
      intraperitoneal sub-lethal dose (50MUgkg(-1)) of 3,3',4,4',5-pentachlorobiphenyl
      (PCB 126) and left for 10d after which standard oxygen consumption and plasma and
      liver metabolites were assessed. PCB 126 exposed trout did not alter standard
      oxygen consumption but did increase plasma glucose concentration implying the
      mobilization of glucose to cope with this exposure regime. Cellular respiration
      was assessed in trout hepatocytes exposed to PCB 126 or PCB 77 (3,3'4,4'
      tetrachlorobiphenyl) two AhR activators but with different potencies (PCB 126?PCB
      77). Mitochondrial respiration was assessed by stimulating complex II with
      succinate and although no increases in respiration were associated with PCB
      exposure in non-stimulated cells, PCB 77 impaired mitochondrial respiration by
      preventing stimulation of complex II respiration and potentially masking any
      actual energetic costs of PCB exposure. These studies suggest that energy is
      mobilized upon exposure to PCBs, however, actual increases in energy demand may
      be overshadowed by impaired mitochondrial respiration.

PMID- 22410625
TI  - Modeling the influence of climate change on the mass balance of polychlorinated
      biphenyls in the Adriatic Sea.
AB  - Climate forcing is forecasted to influence the Adriatic Sea region in a variety
      of ways, including increasing temperature, and affecting wind speeds, marine
      currents, precipitation and water salinity. The Adriatic Sea is intensively
      developed with agriculture, industry, and port activities that introduce
      pollutants to the environment. Here, we developed and applied a Level III
      fugacity model for the Adriatic Sea to estimate the current mass balance of
      polychlorinated biphenyls in the Sea, and to examine the effects of a climate
      change scenario on the distribution of these pollutants. The model's performance
      was evaluated for three PCB congeners against measured concentrations in the
      region using environmental parameters estimated from the 20th century climate
      scenario described in the Special Report on Emission Scenarios (SRES) by the
      IPCC, and using Monte Carlo uncertainty analysis. We find that modeled fugacities
      of PCBs in air, water and sediment of the Adriatic are in good agreement with
      observations. The model indicates that PCBs in the Adriatic Sea are closely
      coupled with the atmosphere, which acts as a net source to the water column. We
      used model experiments to assess the influence of changes in temperature, wind
      speed, precipitation, marine currents, particulate organic carbon and air inflow
      concentrations forecast in the IPCC A1B climate change scenario on the mass
      balance of PCBs in the Sea. Assuming an identical PCBs' emission profile (e.g.
      use pattern, treatment/disposal of stockpiles, mode of entry), modeled fugacities
      of PCBs in the Adriatic Sea under the A1B climate scenario are higher because
      higher temperatures reduce the fugacity capacity of air, water and sediments, and
      because diffusive sources to the air are stronger.

PMID- 22410626
TI  - Congenital nasolacrimal duct obstruction: delineation of anatomic abnormalities
      with 3-dimensional reconstruction.
AB  - OBJECTIVE: To characterize anatomical abnormalities of the distal nasolacrimal
      duct (NLD) in children with congenital obstruction using high-resolution computed
      tomographic imaging. METHODS: The anatomy of the bone and soft tissue of the NLD
      and the postductal anatomy of the inferior meatus in 6 children with a wide
      spectrum of NLD obstructions were imaged by computed tomographic scans and then
      reconstructed in a 3-dimensional viewer. Images were taken from prior axial (5
      children) or coronal (1 child) computed tomographic facial scans at 0.625- or
      1.25-mm mm resolution, respectively. RESULTS: The axial computed tomographic
      images and 3-dimensional reconstructions showed bony obstructions of the distal
      NLD in 3 children, membranous obstructions of the distal NLD in 1 child, and a
      postductal obstruction in the inferior meatus in 1 child. One child had a
      combined soft tissue obstruction of the NLD and post-NLD obstruction.
      CONCLUSIONS: This study provides anatomic evidence of a bony or membranous
      obstruction at the distal portion of the NLD or of a postductal obstruction at
      the inferior meatus in children with congenital NLD obstruction.

PMID- 22410627
TI  - Genotype-phenotype correlations in Bardet-Biedl syndrome.
AB  - OBJECTIVE: To determine whether mutations in different Bardet-Biedl syndrome
      (BBS) genes result in different ocular phenotypes. METHODS: Thirty-seven patients
      from 31 families were enrolled who met the clinical criteria for BBS and for whom
      a BBS mutation had been identified. Seventeen patients harbored mutations in
      BBS1, 10 in BBS10, and 10 in other genes (BBS2, BBS3, BBS5, BBS7, and BBS12). All
      the patients underwent ocular examination; 36 patients had computerized full
      field electroretinograms (ERGs). RESULTS: Visual acuity was significantly better
      in BBS1 patients than in patients with other BBS mutations (P=.01), and a larger
      proportion of BBS1 patients had good (>=20/50) visual acuity (P=.01). The ERG
      amplitudes were significantly higher in BBS1 patients than in patients with other
      BBS mutations in response to 0.5-Hz and 30-Hz flashes (P<.001 for both). All the
      BBS1 patients harbored at least 1 missense mutation compared with only 45% of
      patients with mutations in other BBS genes (P<.001); the rest harbored only null
      alleles. However, multivariate analysis demonstrated that visual acuity or ERG
      amplitude did not depend on the type of mutation present (missense or null) when
      controlling for BBS gene. Prevalences of bone spicule pigmentation and cataract
      were comparable in BBS subtypes. CONCLUSIONS: Patients with BBS1 mutations had a
      milder phenotype than did patients with mutations in other BBS genes. Clinically,
      this manifested as significantly better visual acuity and larger ERG amplitudes.
      CLINICAL RELEVANCE: These phenotypic differences can help guide genetic testing
      and genetic counseling for patients with this syndrome.

PMID- 22410628
TI  - Compatibility of recombinant tissue plasminogen activator and bevacizumab co
      applied for neovascular age-related macular degeneration with submacular
      hemorrhage.
AB  - OBJECTIVE: To investigate the compatibility of recombinant tissue plasminogen
      activator (rtPA) and bevacizumab in vitro because during surgery, rtPA or rtPA
      induced plasmin may cleave and inactivate bevacizumab. METHODS: To simulate the
      intraoperative range of mixing ratios of rtPA, bevacizumab, and subretinal blood,
      we calculated the volumes of 12 submacular hemorrhages (SHs) with a spherical cap
      formula using measurements derived from fundus photographs and spectral-domain
      optical coherence tomographic images. Bevacizumab was incubated with rtPA or
      plasmin before gel electrophoresis with Coomassie blue and silver staining. The
      anti-angiogenetic activity of bevacizumab in the presence of rtPA with or without
      clotted human blood or of plasmin was quantified by vascular endothelial growth
      factor-enzyme-linked immunosorbent assay after incubation with the supernatant of
      porcine retinal pigment epithelium cell cultures. RESULTS: The mean (SD) volume
      of SH was 28.6 (24.7) mm3 (range, 6.2-94.6 mm3). In sodium dodecyl sulfate
      polyacrylamid electrophoresis with Coomassie blue or silver staining, bevacizumab
      displayed characteristic patterns of protein bands. No additional fragments were
      detected in co-application of bevacizumab with either rtPA or plasmin. The anti
      angiogenetic activity of bevacizumab remained unchanged in co-application with
      rtPA with or without blood or plasmin. CONCLUSIONS: We demonstrated the absence
      of cleavage or functional inactivation of bevacizumab by rtPA in an in-vitro
      model of their intraoperative co-application as a treatment of SH. CLINICAL
      RELEVANCE: In clinical practice, rtPA and bevacizumab can be co-applied as a
      treatment for neovascular age-related macular degeneration with SH to
      simultaneously clear SH and reduce choroidal new vessel activity.

PMID- 22410629
TI  - Corneal haze determined by confocal microscopy 2 years after Descemet stripping
      with endothelial keratoplasty for Fuchs corneal dystrophy.
AB  - OBJECTIVE: To quantify corneal light scatter and its relationship to vision after
      Descemet stripping with endothelial keratoplasty (DSEK). METHODS: Eyes with Fuchs
      corneal dystrophy were examined before and 1, 3, 6, 12, and 24 months after DSEK.
      Outcome measures were high- and low-contrast visual acuity, contrast sensitivity,
      and forward light scatter. Corneal reflectivity (backscatter), expressed in
      scatter units (SU), was quantified using in vivo confocal microscopy. RESULTS:
      Comparing 49 study eyes with 35 normal eyes, the mean (SD) corneal subepithelial
      layer was more reflective than normal before (2325 [613] vs 1208 [287] SU,
      P<.001) and through 24 months after DSEK (1760 [432] SU, P<.001). Interface
      reflectivity remained higher than in normal stroma through 24 months (1228 [287]
      vs 827 [188] SU, P<.001). At 1 year, forward light scatter correlated with
      subepithelial reflectivity (r=0.28, P=.01) but not interface reflectivity.
      Recipient age was correlated with improvement in subepithelial reflectivity at 12
      months (r=-0.41, P=.01, 34 eyes) and 24 months (r=-0.36, P=.02, 26 eyes) after
      DSEK, and the improvement of subepithelial haze in eyes of participants aged 62
      years or younger was correlated with improvement in forward light scatter at 12
      months (r=0.52, P=.008) and 24 months (r=0.62, P=.004). CONCLUSIONS: In Fuchs
      corneal dystrophy, the corneal subepithelial region is a more important source of
      forward light scatter than the DSEK interface. Subepithelial haze improves more
      in younger patients and is associated with improvement in forward light scatter.
      CLINICAL RELEVANCE: Visual function after DSEK is affected by residual haze in
      the anterior host cornea more so than the surgical interface. Haze, which likely
      is experienced as glare disability, improves after surgical intervention but
      improves more in younger patients.

PMID- 22410630
TI  - Visual impairment, age-related eye diseases, and cognitive function: the
      Singapore Malay Eye study.
AB  - OBJECTIVE: To describe the associations of visual impairment and major age
      related eye diseases with cognitive function in an older Asian population.
      METHODS: A population-based, cross-sectional study of 1179 participants aged 60
      to 80 years from the Singapore Malay Eye study was conducted. Visual acuity was
      measured using the logMAR vision chart. Cataract and age-related macular
      degeneration were graded using the Wisconsin Cataract Grading System and the
      Wisconsin Age-Related Maculopathy Grading System, respectively. Glaucoma was
      diagnosed using the International Society Geographical and Epidemiological
      Ophthalmology criteria. Diabetic retinopathy was graded using the modified Airlie
      House classification system. Cognitive dysfunction was defined as a locally
      validated Abbreviated Mental Test using education-based cutoff scores. RESULTS:
      After adjusting for age, sex, education level, income, and type of housing,
      persons with visual impairment before refractive correction (odds ratio
      [OR]=2.59; 95% CI, 1.89-3.56) or after refractive correction (OR=1.96; 95% CI,
      1.27-3.02) and those with visual impairment due to cataract (OR=2.75; 95% CI,
      1.35-5.63) were more likely to have cognitive dysfunction. Only moderate to
      severe diabetic retinopathy was independently associated with cognitive
      dysfunction (OR=5.57; 95% CI, 1.56-19.91) after controlling for concurrent age
      related eye diseases. No significant independent associations were observed
      between cataract, age-related macular degeneration, or glaucoma and cognitive
      dysfunction. CONCLUSIONS: Older persons with visual impairment, particularly
      those with visual impairment due to cataract, were more likely to have cognitive
      dysfunction. Furthermore, among the major age-related eye diseases, only diabetic
      retinopathy was associated with cognitive dysfunction.

PMID- 22410631
TI  - Synthesis of 5,10,15-triazaporphyrins--effect of benzo-annulation on the
      electronic structures.
AB  - Novel triazaporphyrins were synthesized using 1,9-dibromodipyrromethene as a key
      starting material. These triazaporphyrins exhibit comparatively intense Soret and
      Q bands in the UV/vis region due to their hybrid properties between porphyrins
      and phthalocyanines.

PMID- 22410632
TI  - Connective tissue diseases: NETing complement in SLE.

PMID- 22410634
TI  - Bone: Performance of fracture risk prediction tools--old and new.

PMID- 22410633
TI  - The pathogenesis of rheumatoid arthritis: new insights from old clinical data?
AB  - Despite their different targets, biologic agents used for blockade of TNF and IL
      6, inhibition of T-cell co-stimulation and B-cell depletion all have similar
      beneficial effects on the outcome of rheumatoid arthritis (RA). This observation
      raises questions as to whether the targets of these therapies might all be
      involved in a common pathogenetic pathway. However, blockade of TNF and IL-6 has
      a similar inhibitory effect on joint damage progression in patients with either
      early or late disease. In comparison, B-cell depletion and inhibition of T-cell
      co-stimulation seem to have a somewhat delayed effect on joint damage (compared
      with cytokine inhibition), which suggests that these approaches affect upstream
      pathogenetic events. This article discusses these disparities and presents
      hypotheses as to whether clinical trial data can be used to determine at which
      point a biologic agent might interfere with the pathogenetic cascade in RA.

PMID- 22410635
TI  - Acute abdominal pain in systemic lupus erythematosus.

PMID- 22410636
TI  - Evolution of the betaGRP/GNBP/beta-1,3-glucanase family of insects.
AB  - The betaGRP/GNBP/beta-1,3-glucanase protein family of insects includes several
      proteins involved in innate immune recognition, such as the beta-glucan
      recognition proteins of Lepidoptera and the Gram-negative bacteria-binding
      proteins of Drosophila. A phylogenetic analysis supported the existence of two
      distinct subfamilies, designated the pattern recognition receptor (PRR) and
      glucanase subfamilies, which originated by gene duplication prior to the origin
      of the Holometabola. In the C-terminal region (CTR) shared by both subfamilies,
      the PRR subfamily has evolved significantly more rapidly at the amino acid
      sequence level than has the glucanase subfamily, implying a relative lack of
      constraint on the amino acid sequence of this region in the PRR subfamily. PRR
      subfamily members also include an N-terminal region (NTR), involved in
      carbohydrate recognition, which is not shared by glucanase subfamily members. In
      comparisons between paralogous PRR subfamily members, there were no conserved
      amino acid residues in the NTR. However, when pairs of putatively orthologous PRR
      subfamily members were compared, the NTR was most often as conserved as the CTR
      or more so. This pattern suggests that the NTR may be important in functions
      specific to the different paralogs, while amino acid sequence changes in the NTR
      may have been important in functional differentiation among paralogs,
      specifically with regard to the types of carbohydrates that they recognize.

PMID- 22410637
TI  - Integrated HIV DNA accumulates prior to treatment while episomal HIV DNA records
      ongoing transmission afterwards.
AB  - OBJECTIVE: We investigated the dynamics of HIV RNA and HIV DNA levels after the
      commencement of raltegravir-based antiretroviral therapy (ART) in primary (PHI)
      and chronically HIV-infected (CHI) individuals (the PINT study). DESIGN: We
      recruited 8 PHI and 8 CHI ART-naive individuals who commenced a 1-year
      combination regimen of Truvada and the integrase inhibitor raltegravir. METHODS:
      Nonlinear mixed effects modelling was used to determine multiphasic decay of
      plasma HIV RNA levels (pVL), as well as dynamics of total, episomal [2-long
      terminal repeats (LTR)] and integrated HIV DNA in CD4 T cells from peripheral
      blood. RESULTS: Although pVL decreased faster through first and second phase for
      PHI individuals there was no difference in the final level reaching a mean of 9
      copies/ml by week 16 that was maintained thereafter. Total HIV DNA and integrated
      HIV DNA levels from CHI patients were significantly higher than from PHI
      patients. However, at no time did 2-LTR levels differ between groups. Of note, 2
      LTR circles exhibited an initial increase peaking at week 3 followed by biphasic
      decay with a half-life of 29 days. Second phase integrated HIV DNA levels were
      significantly correlated with duration of infection and consistent with this form
      of infection occurring at approximately 100 000 integration events per day in the
      absence of ART, achieving its 50% level 2 years after infection. CONCLUSIONS:
      Integrated HIV DNA levels accumulate with duration of untreated HIV infection.
      The relatively short half-life and high levels of 2-LTR circles after 1 year
      support continued HIV transmission during ART.

PMID- 22410639
TI  - Effects of soil chemistry on tropical forest biomass and productivity at
      different elevations in the equatorial Andes.
AB  - The dependence of aboveground biomass and productivity of tropical forests on
      soil fertility is not fully understood, since previous studies yielded
      contrasting results. Here, we quantify aboveground biomass (AGB) and stem wood
      production, and examine the impact of soil chemistry on these parameters in
      mature tropical forest stands of the equatorial Andes in Ecuador. In 80 plots of
      0.04 ha at four elevation levels (500, 1,000, 1,500 and 2,000 m a.s.l., total
      sample area = 3.2 ha), we measured ten important soil chemical parameters,
      inventoried all trees >=10 cm dbh and monitored stem diameter growth with
      dendrometer tapes in 32 plots. Top canopy height and stem density significantly
      decreased from 500 to 2,000 m, while tree basal area increased and AGB remained
      invariant (344 +/- 17 Mg DM ha(-1), mean +/- SE) with elevation. Wood specific
      gravity (WSG) showed a significant, but small, decrease. Stem wood production
      decreased from 4.5 to 3.2 Mg DM ha(-1) year(-1) along the transect, indicating a
      higher biomass turnover at lower elevations. The only soil variable that covaried
      with AGB was exchangeable K in the topsoil. WSG increased with decreases in N
      mineralisation rate, soil pH and extractable Ca and P concentrations. Structural
      equation modelling (SEM) revealed that nitrogen availability acts on stem wood
      production only indirectly through a negative relation between N mineralisation
      rate and WSG, and a positive effect of a lowered WSG on stem growth. The SEM
      analysis showed neither direct nor indirect effects of resin-extractable P on
      wood production, but a negative P influence on AGB. We conclude that nitrogen
      availability significantly influences productivity in these Andean forests, but
      both N and P are affecting wood production mainly indirectly through alterations
      in WSG and stem density; the growth-promoting effect of N is apparently larger
      than that of P.

PMID- 22410638
TI  - Glycemic control after stomach-sparing duodenal-jejunal bypass surgery in
      diabetic patients with low body mass index.
AB  - BACKGROUND: Bariatric surgery frequently results in the resolution of type 2
      diabetes mellitus (T2DM). One of the many factors that could explain such
      findings is the duodenal exclusion of the alimentary tract. To test this
      hypothesis, a surgical model that induces glycemic control without significant
      weight loss would be ideal. In the present study, we evaluated the early
      metabolic changes that occur in overweight diabetic patients after laparoscopic
      duodenal-jejunal bypass (DJB) and determined the factors associated with success
      in T2DM resolution. The setting was a private practice. METHODS: A total of 35
      patients (20 men and 15 women) were included in the present study. The mean
      preoperative body mass index was 28.4 +/- 2.9 kg/m(2). DJB was performed in all
      patients, and the anthropometric data and blood samples were collected at
      baseline (preoperatively) and 3, 6, 9, and 12 months after surgery. Success was
      defined when patients reached a glycated hemoglobin level of <7% without diabetic
      medication. RESULTS: T2DM remission was observed in 14 (40%) of 35 patients. No
      differences in the homeostasis model assessment insulin resistance index levels
      and patient weight were observed before and 12 months after DJB surgery. Gender,
      duration of T2DM, previous use of insulin, preoperative homeostasis model
      assessment insulin resistance index, and C-peptide levels were not significant
      predictive factors of success or nonsuccess. The only factor that significantly
      predicted postoperative positive outcomes was a waist circumference reduction of
      >= 7% compared with baseline within the first 6 months after surgery. CONCLUSION:
      DJB improves glycemic control; however, it does not increase insulin sensitivity
      in overweight diabetic patients. These changes were observed without significant
      weight loss.

PMID- 22410640
TI  - The involvement of oxidants and NF-kappaB in cytokine-induced MMP-9 synthesis by
      bone marrow-derived osteoprogenitor cells.
AB  - OBJECTIVE AND DESIGN: The activity of immune cells affects the balance between
      bone mineralization and resorption carried out by the opposing actions of
      osteoblasts and osteoclasts, respectively. This study was aimed at determining
      the possible interaction between inflammatory conditions and collagen type I
      degrading MMP (mainly MMP-2 and MMP-9) synthesis and secretion in rat
      osteoprogenitors. MATERIALS AND METHODS: The study was performed using primary
      rat bone marrow-derived osteoprogenitors during their advanced osteogenesis.
      Biochemical, immunohistochemical, and molecular biology techniques were used to
      investigate the influence of pro-inflammatory cytokines on MMP-2 and MMP-9
      synthesis and secretion in osteoprogenitors. RESULTS: Results indicated that both
      synthesis and secretion of MMPs (MMP-1, -2, -8, -9, and -13) were significantly
      induced after pro-inflammatory cytokine treatments, except MMP-2, whose levels
      remained unchanged. NF-kappaB (nuclear factor kappa-light chain enhancer of
      activated B cells) inhibition assays showed that induced MMP-9 secretion by
      inflammatory cytokines was mediated by activation of NF-kappaB via the classical
      pathway and that oxidants play a significant role in this signal transduction
      pathway. In contrast, no such effect was observed for synthesis of MMP-2.
      CONCLUSIONS: These results indicate the possibility that inflammatory processes
      may trigger osteoblasts to absorb bone by secreting elevated levels of MMPs
      capable of degrading collagen type I, especially MMP-9 which is upregulated due
      to increased NF-kappaB transcription activity.

PMID- 22410641
TI  - Tofogliflozin, a potent and highly specific sodium/glucose cotransporter 2
      inhibitor, improves glycemic control in diabetic rats and mice.
AB  - Sodium/glucose cotransporter 2 (SGLT2) is the predominant mediator of renal
      glucose reabsorption and is an emerging molecular target for the treatment of
      diabetes. We identified a novel potent and selective SGLT2 inhibitor,
      tofogliflozin (CSG452), and examined its efficacy and pharmacological properties
      as an antidiabetic drug. Tofogliflozin competitively inhibited SGLT2 in cells
      overexpressing SGLT2, and K(i) values for human, rat, and mouse SGLT2 inhibition
      were 2.9, 14.9, and 6.4 nM, respectively. The selectivity of tofogliflozin toward
      human SGLT2 versus human SGLT1, SGLT6, and sodium/myo-inositol transporter 1 was
      the highest among the tested SGLT2 inhibitors under clinical development.
      Furthermore, no interaction with tofogliflozin was observed in any of a battery
      of tests examining glucose-related physiological processes, such as glucose
      uptake, glucose oxidation, glycogen synthesis, hepatic glucose production,
      glucose-stimulated insulin secretion, and glucosidase reactions. A single oral
      gavage of tofogliflozin increased renal glucose clearance and lowered the blood
      glucose level in Zucker diabetic fatty rats. Tofogliflozin also improved
      postprandial glucose excursion in a meal tolerance test with GK rats. In db/db
      mice, 4-week tofogliflozin treatment reduced glycated hemoglobin and improved
      glucose tolerance in the oral glucose tolerance test 4 days after the final
      administration. No blood glucose reduction was observed in normoglycemic SD rats
      treated with tofogliflozin. These findings demonstrate that tofogliflozin
      inhibits SGLT2 in a specific manner, lowers blood glucose levels by increasing
      renal glucose clearance, and improves pathological conditions of type 2 diabetes
      with a low hypoglycemic potential.

PMID- 22410643
TI  - Value of different staging systems for predicting neurological outcome in
      childhood tuberculous meningitis.
AB  - BACKGROUND: The stage of tuberculous meningitis (TBM) at presentation is strongly
      associated with prognosis. OBJECTIVE: To compare different staging systems for
      TBM in predicting outcome. METHODS: The associations of different staging systems
      with neurological outcome were assessed  using clinical, diagnostic and outcome
      data of 554 TBM children admitted to Tygerberg Children's Hospital from January
      1985 to April 2005. RESULTS: The refined Medical Research Council (MRC) scale
      after 1 week (84%, 95%CI 81-88) had the highest discriminatory power in
      predicting neurological  morbidity. The Glasgow Coma Score (GCS) on admission,
      GCS after 1 week, the 'refined' MRC scale on admission and Tygerberg Children's
      Hospital (TCH) staging method all had excellent discriminatory powers in
      predicting outcome. Improvement of staging after 1 week occurred in children  who
      did not have signs of raised intracranial pressure (P = 0.004) or brainstem
      dysfunction on admission (P = 0.030). CONCLUSIONS: The 'refined' MRC scale 1 week
      after diagnosis showed the best association with neurological outcome after 6
      months of treatment.  The excellent discriminatory power of the TCH scale and its
      simplicity of use make it the ideal scale for use in resource-poor settings.

PMID- 22410642
TI  - Shared decision making and other variables as correlates of satisfaction with
      health care decisions in a United States national survey.
AB  - OBJECTIVE: The purpose of this study was to examine the relationship between
      shared decision-making (SDM) and satisfaction with decision (SWD) within a larger
      survey of patient decision-making in health care consultations. METHODS: A
      randomly selected age-proportionate national sample of adults (aged 21-70 years)
      stratified on race, ethnicity, and gender (N=488) was recruited from a health
      research volunteer registry and completed an online survey with reference to a
      recent health consultation. Measures included the shared decision making-9
      questionnaire (SDM-Q-9), Satisfaction With Decision (SWD) scale,
      sociodemographic, health, and other standardized decision-making measures.
      Forward selection weighted multiple regression analysis was used to model
      correlates of SWD. RESULTS: After controlling for sociodemographic variables, SDM
      Q-9 total score was associated with SWD, adjusted R(2)=.368, p<.001. Three of
      nine SDM-Q-9 items accounted for significant proportions of variance in SWD.
      CONCLUSION: SDM was positively associated with SWD and was strongest for three
      areas of SDM: patients being helped in a health care consultation with
      understanding information, with treatment preference elicitation, and with
      weighing options thoroughly. PRACTICE IMPLICATIONS: By identifying variables such
      as SDM that are associated with SWD, health care interventions can better target
      modifiable factors to enhance satisfaction and other outcomes.

PMID- 22410644
TI  - The effect of continuous positive airway pressure treatment for obstructive sleep
      apnea syndrome on the ocular surface.
AB  - PURPOSE: To evaluate the effect of continuous positive airway pressure (CPAP)
      treatment for obstructive sleep apnea syndrome on the ocular surface. METHODS:
      This is a prospective, sectional cohort study of 80 eyes of 40 patients diagnosed
      with obstructive sleep apnea syndrome. Routine ophthalmologic examination and
      ocular surface evaluation, including biomicroscopy, Schirmer 1 testing, tear
      break-up time measurement, ocular surface staining, and conjunctival impression
      cytology, were performed in both of each patient's eyes before and 4 months after
      starting CPAP therapy. RESULTS: After CPAP therapy, increases in squamous
      metaplasia (Nelson classification: t = 0.34, P = 0.014) and Schirmer 1 score (t =
      3.20, P = 0.008), and decreases in tear break-up time (t = -1.38, P = 0.008) in
      the right eyes were statistically significant, as compared with the pretreatment
      values. Although these parameters changed in a similar fashion in the left eyes,
      differences between the pre-CPAP and post-CPAP values were not significant.
      CONCLUSIONS: The findings indicate that CPAP therapy increased ocular irritation,
      tear evaporation, and squamous metaplasia in the conjunctiva of the patients'
      right and left eyes. Although the parameters measured were similar in both eyes
      before CPAP therapy, these parameters changed significantly after CPAP therapy
      only in the right eyes. The observed differences between the right and left eyes
      require further investigation to determine the possible effects of sleeping
      position, CPAP mask displacement, and the other factors involved.

PMID- 22410645
TI  - A preservative-and-fluorescein interaction model for benign multipurpose solution
      associated transient corneal hyperfluorescence.
AB  - PURPOSE: Multipurpose contact lens solution (MPS)/preservative-associated
      transient corneal hyperfluorescence has been suggested to represent corneal
      injury. To determine the validity of this assumption, the molecular-level
      interactions of common disinfectants in soft contact lens MPS and the corneal
      epithelium using an in vitro model were assessed. METHODS: A liposome-based model
      of the corneal epithelial surface was developed and used to assess the
      interactions of polyhexamethylene biguanide (PHMB), polyquaternium-1 (PQ-1), and
      fluorescein with membrane components and the effects of PHMB and PQ-1 on membrane
      integrity. The fluorescence anisotropy (a measure of interactions between
      molecules) was determined. Liposome integrity was assessed by measuring the
      liposome melting point temperature. RESULTS: Free fluorescein did not associate
      with the liposome (P>0.4). Both fluorescein-tagged PHMB and PQ-1 associated with
      liposomes (P<0.002 and P<=0.01, respectively); however, only PHMB induced free
      fluorescein association with membrane components. At physiological temperature,
      no significant shift in the melting point temperature was observed when liposomes
      were exposed to PHMB from 0 to 100 ppm (P>0.05). In contrast, exposure of >7 ppm
      PQ-1 disrupted the liposomes. CONCLUSIONS: Based on this study, PHMB-to-liposome
      bilayer interaction is nondestructive, even at concentrations 100 times higher
      than found in commercially available MPS products. In contrast, PQ-1-to-liposome
      bilayer interaction led to liposome disruption. This study presents molecular
      level evidence to support that preservative-associated transient corneal
      hyperfluorescence is a benign transient phenomenon and its evaluation clinically
      may be an ambiguous strategy for determining biocompatibility and cell surface
      integrity.

PMID- 22410646
TI  - The safety and efficacy of live attenuated influenza vaccine in young children
      with asthma or prior wheezing.
AB  - In the European Union and Canada, an Ann Arbor strain live attenuated influenza
      vaccine (LAIV) is approved for use in children aged 2-17 years, including those
      with mild to moderate asthma or prior wheezing. The safety and efficacy of LAIV
      versus trivalent inactivated influenza vaccine (TIV) in children with asthma aged
      6-17 years have been demonstrated. However, few data are available for children
      younger than 6 years of age with asthma or prior wheezing. Safety and efficacy
      data were collected for children aged 2-5 years with asthma or prior wheezing
      from two randomized, multinational trials of LAIV and TIV (N = 1,940). Wheezing,
      lower respiratory illness, and hospitalization were not significantly increased
      among children receiving LAIV compared with TIV. Increased upper respiratory
      symptoms and irritability were observed among LAIV recipients (p < 0.05).
      Relative efficacies were consistent with the results observed in the overall
      study populations, which demonstrated fewer cases of culture-confirmed influenza
      illness in LAIV compared with TIV recipients. Study results support the safety
      and efficacy of LAIV among children aged 2-17 years with mild to moderate asthma
      or a history of wheezing. Data regarding LAIV use are limited among individuals
      with severe asthma or active wheezing within the 7 days before vaccination.

PMID- 22410648
TI  - White matter hyperintensities predict amyloid increase in Alzheimer's disease.
AB  - Impaired amyloid clearance probably contributes to increased amyloid deposition
      in sporadic Alzheimer's disease (AD). Diminished perivascular drainage due to
      cerebral small-vessel disease (CSVD) has been proposed as a cause of reduced
      amyloid clearance. White matter hyperintensities (WMHs) are considered to reflect
      CSVD and can be measured using fluid-attenuated inversion recovery (FLAIR)
      magnetic resonance imaging (MRI). Amyloid deposition can be determined in vivo
      using Pittsburgh compound B ([11C]PiB) positron emission tomography (PET). We
      aimed to elucidate the association between WMH and the progression of amyloid
      deposition in patients with AD. Twenty-two patients with probable AD underwent
      FLAIR-MRI and [11C]PiB-PET examinations at baseline (BL) and after a mean follow
      up (FU) interval of 28 months. The relationship between BL-WMH and the
      progression of cerebral amyloid between BL and FU was examined using a regions-of
      interest (ROI) approach. The region-specific variability of this relationship was
      analyzed using a voxel-based method. The longitudinal analysis revealed a
      statistically significant association between the amount of BL-WMH and the
      progression of amyloid load between BL and FU (p = 0.006, adjusted R2 = 0.375,
      standardized coefficient beta = 0.384). The association was particularly observed
      in parieto-occipital regions and tended to be closer in regions adjacent to the
      brain surface. According to our knowledge, this is the first in vivo study in
      human being supporting the hypothesis that impaired amyloid clearance along
      perivascular drainage pathways may contribute to beta-amyloid deposition in
      sporadic AD. The extent of WMH might be a relevant factor to be assessed in
      antiamyloid drug trials.

PMID- 22410647
TI  - Analysis of the hexanucleotide repeat in C9ORF72 in Alzheimer's disease.
AB  - Frontotemporal lobar degeneration (FTLD) is a highly familial neurodegenerative
      disease. It has recently been shown that the most common genetic cause of FTLD
      and amyotrophic lateral sclerosis (ALS) is a hexanucleotide repeat expansion in
      C9ORF72. To investigate whether this expansion was specific to the FTLD/ALS
      disease spectrum, we genotyped the hexanucleotide repeat region of C9ORF72 in a
      large cohort of patients with Alzheimer's disease (AD). A normal range of repeats
      was found in all cases. We conclude that the hexanucleotide repeat expansion is
      specific to the FTLD/ALS disease spectrum.

PMID- 22410649
TI  - Hearing outcomes following microvascular decompression for hemifacial spasm.
AB  - PURPOSE: Facial nerve microvascular decompression (MVD) for hemifacial spasm
      (HFS) provides relief to most patients. Due to the proximity of the cochlear and
      facial nerves, hearing loss is a potential MVD complication, however, there is a
      wide range in the reported incidence of hearing loss (HL) in the literature. In
      order to better understand the HL incidence in our MVD population, we utilized
      the combination of speech discrimination scores (SDS) and air and bone pure tone
      threshold averages (PTA) to identify patients with no hearing change,
      sensorineural hearing loss, or conductive hearing loss. We also assessed the
      predictive value of patient-reported hearing deficits on the ultimate audiometric
      diagnosis of hearing loss. METHODS: One hundred and fifty one patients underwent
      facial nerve MVD at the University of Pittsburgh Medical Center between January
      2000 and December 2007. Peri-operative audiometric data, including changes in air
      and bone pure tone thresholds and speech discrimination scores, were analyzed
      retrospectively. Criteria from the 1995 American Academy of Otolaryngology
      Committee on Hearing and Equilibrium consensus were used to analyze post
      operative hearing loss. Patient-reported hearing disturbances obtained in the
      immediate post-operative period were compared to seven-day post-operative
      conductive and sensorineural HL status. RESULTS: Non-functional, non-serviceable
      HL (Class D) occurred in 6.6% of patients, while 10.6% developed cumulative non
      functional HL (Class C and D). Twenty-nine patients (18.7%) exhibited conductive
      HL. While patient-reported complaints were predictive of Class C/D HL (<0.0001)
      with a 56.3% sensitivity and 92.6% specificity, patient-reported complaints were
      not strongly associated with conductive HL status (p = 0.369) with 17.2%
      sensitivity and 88.5% specificity. CONCLUSIONS: Perioperative hearing
      evaluations, in conjunction with careful scrutiny of patient complaints and air
      bone pure tone testing enables the physician to more precisely quote complication
      rates and rapidly distinguish potentially reversible conductive hearing
      pathologies from permanent sensorineural disorders.

PMID- 22410650
TI  - Starfruit neurotoxicity mimicking an acute brainstem stroke.

PMID- 22410651
TI  - Perimesencephalic subarachnoid hemorrhage associated with a painless, pupillary
      involving third cranial nerve palsy: case report and literature review.

PMID- 22410652
TI  - Evolutionary and biogeographic history of weasel-like carnivorans (Musteloidea).
AB  - We analyzed a concatenated (8492 bp) nuclear-mitochondrial DNA data set from 44
      musteloids (including the first genetic data for Lyncodon patagonicus) with
      parsimony, maximum likelihood, and Bayesian methods of phylogenetic and
      biogeographic inference and two Bayesian methods of chronological inference. Here
      we show that Musteloidea emerged approximately 32.4-30.9 million years ago (MYA)
      in Asia, shortly after the greenhouse-icehouse global climate shift at the Eocene
      Oligocene transition. During their Oligocene radiation, which proceeded wholly or
      mostly in Asia, musteloids diversified into four primary divisions: the
      Mephitidae lineage separated first, succeeded by Ailuridae and the divergence of
      the Procyonidae and Mustelidae lineages. Mustelidae arose approximately 16.1 MYA
      within the Mid-Miocene Climatic Optimum, and extensively diversified in the
      Miocene, mostly in Asia. The early offshoots of this radiation largely evolved
      into badger and marten ecological niches (Taxidiinae, Melinae, Mellivorinae,
      Guloninae, and Helictidinae), whereas the later divergences have adapted to other
      niches including those of weasels, polecats, minks, and otters (Mustelinae,
      Ictonychinae, and Lutrinae). Notably, and contrary to traditional beliefs, the
      morphological adaptations of badgers, martens, weasels, polecats, and minks each
      evolved independently more than once within Mustelidae. Ictonychinae (which is
      most closely related to Lutrinae) arose approximately 9.5-8.9 MYA, most likely in
      Asia, where it diverged into the Old World Ictonychini (Vormela, Poecilictis,
      Ictonyx, and Poecilogale) and New World Lyncodontini (Lyncodon and Galictis)
      lineages. Ictonychini presumably entered Africa during the Messinian Salinity
      Crisis (at the Miocene-Pliocene transition), which interposed the origins of this
      clade (approximately 6.5-6.0 MYA) and its African Poecilictis-Ictonyx-Poecilogale
      subclade (approximately 4.8-4.5 MYA). Lyncodontini originated approximately 2.9
      2.6 MYA at the Pliocene-Pleistocene transition in South America, slightly after
      the emergence of the Panamanian land bridge that provided for the Great American
      Biotic Interchange. As the genera Martes and Ictonyx (as currently circumscribed)
      are paraphyletic with respect to the genera Gulo and Poecilogale, respectively,
      we propose that Pekaniaand Poecilictis be treated as valid genera and that
      "Martes"pennanti and "Ictonyx"libyca, respectively, be assigned to these genera.

PMID- 22410653
TI  - Recurrent intracerebral hemorrhage in patients with hypertension is associated
      with APOE gene polymorphism: a preliminary study.
AB  - BACKGROUND: Recurrent intracerebral hemorrhage (ICH) in patients with
      hypertension has been reported in Asia and is attributed to poor control of blood
      pressure, but there may be a genetic basis. This study evaluates the roles of
      apolipoprotein E (APOE) and alpha-1 antichymotrypsin (ACT) genes in patients with
      recurrent hypertensive ICH and compares patients with nonrecurring hypertensive
      ICH and normal controls. METHODS: Thirty-three recurrent and 101 nonrecurrent
      patients with hypertension and ICH were included. The demographic, stroke risk
      factors, and computed tomographic or magnetic resonance imaging findings were
      recorded. Magnetic resonance angiography or digital subtraction angiography and
      vasculitic profile were done in recurrent group to exclude secondary causes of
      ICH. APOE and ACT gene polymorphisms were assessed with polymerase chain reaction
      studies in patients with ICH and 188 healthy controls. RESULTS: The demographic
      and clinical variables were similar in patients with recurrent and nonrecurrent
      ICH, but patients with recurrent ICH were older (61.1 vs 57.2 years). In the
      recurrent ICH group, only 7 (10%) out of 69 episodes were lobar; the remaining
      were deep-seated hematomas. In the nonrecurrent group, 7 (6.9%) patients had
      lobar ICH. The E2 (odds ratio 4.32; 95% confidence interval 1.65-11.28; P = .003)
      and E4 alleles of APOE (odds ratio 11.33; 95% confidence interval 5.37-23.02; P <
      .0001) were significantly related to recurrent ICH compared to healthy controls.
      The E4 allele was also independently related to recurrent compared to
      nonrecurrent ICH, even after adjustment for stroke risk factors (odds ratio
      25.99; 95% confidence interval 11.65-57.97; P < .0001). ACT gene polymorphism,
      however, was not related to recurrent ICH compared to controls and nonrecurrent
      ICH. CONCLUSIONS: APOE polymorphism may contribute to the recurrence of
      hypertensive ICH.

PMID- 22410654
TI  - The relationship between knowledge and risk for heart attack and stroke.
AB  - BACKGROUND: Stroke and myocardial infarction (MI) represent 2 of the leading
      causes of death in the United States. The early recognition of risk factors and
      event symptoms allows for the mitigation of disability or death. We sought to
      compare subject knowledge of stroke and MI, assess subject risk for
      cardiovascular disease, and determine if an association exists between knowledge
      and risk. METHODS: In this cross-sectional survey, adult, non-health care
      professionals were presented with a written knowledge test and risk assessment
      tool. Subjects were classified into 3 categories of cardiovascular risk.
      Associations were then calculated between knowledge, risk, and population
      demographics. RESULTS: Of 500 subjects approached, 364 were enrolled. The
      subjects were mostly white, middle-aged, and high school educated. Gender and
      income were evenly distributed. Forty-eight (14%) subjects were identified as
      ideal risk, 130 (38%) as low risk, and 168 (49%) as moderate/high risk. MI and
      stroke knowledge scores decreased as cardiovascular risk increased (85%, 79%, and
      73% for ideal, low, and moderate/high risk groups, respectively; P < .001). In
      addition, regardless of risk category, stroke knowledge scores were always lower
      than heart attack knowledge scores. CONCLUSIONS: Knowledge about stroke and MI
      was modest, with knowledge of MI exceeding that of stroke at every level of risk.
      Subjects with higher risk were less knowledgeable about the stroke signs,
      symptoms, and risk factors than those of MI.

PMID- 22410655
TI  - Interleukin-6 gene -174 G/C promoter polymorphism predicts severity and outcome
      in acute ischemic stroke patients from north India.
AB  - BACKGROUND: A guanine/cytosine (G/C) substitution occurring in position -174 of
      the interleukin-6 (IL-6) gene promoter changes the expression of IL-6 circulating
      proteins. We evaluated the occurrence of IL-6 -174 G/C polymorphism in patients
      with acute ischemic stroke and studied its association with stroke severity,
      outcome, and mortality. METHODS: One hundred patients with acute ischemic stroke
      and 120 age and sex-matched healthy controls were studied. Genotyping was
      performed using polymerase chain reaction and restriction enzyme analysis. Serum
      levels of IL-6 were measured using enzyme-linked immunosorbent assay. Stroke was
      classified using Trial of Org 10172 in Acute Stroke Treatment (TOAST)
      classification. Severity was assessed by the National Institutes of Health Stroke
      Scale. Outcome measures included modified Rankin Scale (mRS) and Barthel Index
      (BI) scores at 7 days and 3 and 6 months. Mortality/survival was assessed using
      the Kaplan-Meier analysis. RESULTS: The frequency of GG, GC, and CC genotypes did
      not differ significantly between cases and controls. No association was seen
      between TOAST subtype and genotype. At the time of admission, stroke was more
      severe in patients with the GC genotype (P = .03) and less severe in the GG
      genotype (P = .04). The GC genotype was also associated with higher serum IL-6
      levels and poor short-term (BI P = .001; mRS P = .003) and long-term outcomes (BI
      P = 9 * 10(-5); mRS P = 9 * 10(-5)), while the GG genotype had significantly
      lower serum IL-6 levels and better short and long-term outcomes (BI P = 3 * 10(
      5); mRS P = 2 * 10(-4)). There was significantly lesser mortality in the GG
      genotype and more in the GC genotype based on the Kaplan-Meier analysis.
      CONCLUSIONS: Patients with the GC genotype had more severe strokes with poorer
      short and long-term outcomes and increased mortality. The GG genotype was
      associated with less severe strokes, better short and long-term prognosis, and
      survival. The GG genotype appears to be protective against stroke severity,
      outcome, and mortality.

PMID- 22410656
TI  - The external browpexy.
AB  - PURPOSE: To introduce and describe the author's experience with the external
      browpexy, a minimally invasive transcutaneous variant of the trans-blepharoplasty
      temporal brow suspension (internal browpexy). METHODS: The charts of patients who
      underwent an external browpexy over a 2-year period by the author are reviewed.
      Excluded from the study are patients with a history of previous forehead/eyebrow
      or eyelid surgery. The surgical procedure is described in depth, representative
      patient photographs are presented to assess outcome, and results and
      complications are reviewed. RESULTS: Twenty-eight patients are included in the
      study. The average age is 62 years (range 51-76), and the average follow-up is 6
      months (range 2-12). Eighteen patients are men, 5 patients had unilateral
      surgery, and only 1 patient noted a subtle postoperative scar. All patients
      (including the one with the mild scar) were pleased with their surgical results.
      CONCLUSIONS: The external browpexy is a straightforward procedure, easily
      mastered and has subjectively yielded excellent outcomes with high patient
      satisfaction over a 6-month average follow-up. In the author's experience, the
      brow incision has consistently healed without perceptible scar, and over this
      timeframe, the procedure has subjectively been shown to be a reliable temporal
      brow elevator/stabilizer. The procedure is presented as an alternative to the
      internal browpexy to aid in enhancing upper blepharoplasty outcomes.

PMID- 22410657
TI  - Stereotactic fractionated radiotherapy for cavernous venous malformations
      (hemangioma) of the orbit.
AB  - PURPOSE: Cavernous malformations (hemangioma) of the orbit, when symptomatic, can
      often be treated successfully with complete surgical excision. However, when they
      involve local structures in their capsule, are situated in the orbital apex, or
      extend through the superior orbital fissure, the risks of surgery increase
      significantly. In such cases, alternative treatment modalities can be explored.
      In this study, the authors report on the use of fractionated stereotactic
      radiotherapy (SFRT) for the treatment of surgically complicated cavernous
      malformations. METHODS: In this retrospective cohort study, the authors reviewed
      the clinical and radiologic records of 5 patients treated with SFRT over the past
      5 years. RESULTS: Patients ranged in age from 30 to 65 years, and 3 out of 5 were
      female. Two cases involved the cavernous sinus, one involved the ophthalmic
      artery, one involved the posterior ciliary artery, and the last traversed the
      superior orbital fissure. Four had significant visual field defects. Each was
      treated with SFRT. A total dose of 4000 cGy divided into 20,200 cGy fractions was
      applied for 3 cases, while 2 other cases were treated with total doses of 4563
      and 4959 cGy divided into 28 * 162 cGy and 29 * 171 cGy fractions, respectively.
      Rapid resolution of visual field defect was noted by 3 months, and overall tumor
      shrinkage was on average 60% (range: 32-79%). Follow-up was on average 23.4
      months (range: 5-50 months). No complications of treatment were noted.
      CONCLUSIONS: For symptomatic cavernous malformations demonstrating anatomical
      position that may increase risk of surgical excision, SFRT is an effective and
      safe method to control lesion size and improve visual function.

PMID- 22410658
TI  - A controlled study of topical 0.25% timolol maleate gel for the treatment of
      cutaneous infantile capillary hemangiomas.
AB  - PURPOSE: To evaluate the efficacy of topical 0.25% timolol maleate gel for the
      treatment of cutaneous infantile capillary hemangiomas. METHODS: A retrospective,
      consecutive, nonrandomized, comparative single-masked cohort study of all
      patients presenting with nonvision-threatening periocular infantile capillary
      hemangiomas between August 2007 and January 2011 was performed. Parents chose
      twice daily topical 0.25% timolol maleate gel or observation. Photographs were
      taken at all visits and subsequently evaluated by masked examiners for change in
      lesion size, color, and thickness. Lesions were clinically defined as
      superficial, mixed, or deep. The primary outcome was response to treatment at 2
      months, categorized as good (size decreased .50%), moderate (decrease 0-50%), or
      poor (enlarged or caused visually significant ptosis or induced astigmatism). The
      secondary outcome was response at latest follow-up visit. RESULTS: Thirteen
      children received timolol, and 10 children were observed, with mean ages at
      presentation of 4.8 and 3.7 months (p 5 0.31), respectively. In the treated
      group, good response was observed in 8 (61.5%) infants, moderate response was
      seen in 4 (30.8%), and poor response was seen in one patient (7.7%). In the
      observed group, 0 (0%) demonstrated good response, one (10%) demonstrated
      moderate response, and 9 demonstrated poor response (90%) (p , 0.001). Responses
      were consistent on long-term follow-up (range 3-41 months). Both superficial (n 5
      5; 100% good response) and mixed (n 5 7; 43% good, 57% moderate) lesions
      responded well to timolol; the one deep lesion did not. No adverse ocular or
      systemic effects were observed. CONCLUSIONS: Topical timolol maleate gel 0.25% is
      effective in treatment of nonvision-threatening infantile capillary hemangiomas
      with a superficial component. Response at 2 months is stable over time.

PMID- 22410659
TI  - Sclerosing orbital inflammation and systemic disease.
AB  - PURPOSE: To determine the clinical differences between sclerosing orbital
      inflammation (SOI) isolated to the orbit and SOI manifesting as part of systemic
      inflammatory disease. METHODS: For the case series, the authors identified
      patients with SOI from their patient database and tabulated their clinical data.
      For the literature review, a search for case reports of SOI in the English
      literature was performed. The clinical data of each were tabulated and analyzed.
      RESULTS: For the case series, 13 cases of SOI were identified, 2 with multifocal
      fibrosclerosis (MFF) and 4 with other systemic inflammatory diseases. Of the 5
      bilateral cases, 4 (80%) had some form of systemic inflammatory disease including
      2 with MFF. Only 2 (25%) of the 8 unilateral cases had systemic inflammatory
      disease. The average ESR was 7 mm/hour for those without systemic disease and 41
      mm/hour with evidence of systemic disease (p = 0.038). For the literature review,
      the authors identified 68 case reports of SOI not previously reported in large
      case series, 34 associated with MFF, 5 associated with other systemic disease,
      and 29 not associated with any systemic disease. Sixty-nine percent of cases with
      systemic disease had bilateral orbital involvement, whereas only 3.6% of those
      without systemic disease were bilateral (p = 1.15 * 10(-8)). Twenty of the cases
      with MFF noted ESR (83 mm/hour, mean), 95% of which were above normal. ESR was
      noted in only one non-MFF, nonsystemic disease case and was normal. CONCLUSIONS:
      SOI in the setting of MFF or other systemic inflammatory disease is often
      bilateral and associated with an elevated ESR.

PMID- 22410660
TI  - Bacterial and mucopeptide concretions of the lacrimal drainage system:  an
      analysis of 30 cases.
AB  - PURPOSE: To demonstrate the histopathologic characteristics of different types of
      lacrimal drainage system concretions with clinical correlations. METHODS: Thirty
      lacrimal drainage system concretions submitted to the Cogan Eye Pathology
      Laboratory at the Massachusetts Eye and Ear Infirmary over a 2-year period were
      reviewed. Concretions were studied in detail using their histopathologic staining
      features as revealed with hematoxylin and eosin, Gomori methenamine silver,
      periodic acid-Schiff, iron stain, and Brown-Hopps tissue gram stain. A separate
      retrospective chart review was conducted for each patient to identify any
      clinical correlations. RESULTS: Two major forms of concretions were identified
      histopathologically: mucopeptide (7) and bacterial (20). Mucopeptide concretions
      were found exclusively within the lacrimal sac, while bacterial concretions were
      found chiefly in the canaliculus. A third category of "mixed" concretions with
      substantial mucopeptide and bacterial characteristics comprised 3 specimens.
      Bacterial concretions consisted of large matted masses of filamentous, presumed
      Actinomyces organisms that were easily identified with the Grocott's methenamine
      silver stain; they were frequently cocolonized at their edges with coccal
      bacterial forms. Mucopeptide concretions were generally devoid of cellular
      elements and were composed of broad bland whorls of diffusely eosinophilic,
      acellular, periodic acid-Schiff-positive material punctuated by lacunae. They
      were often cocolonized by small numbers of bacterial cocci and occasional fungi.
      Culture results disclosed low virulence species. All 3 types of concretions
      predominated in women. Patients with bacterial concretions frequently had dry eye
      symptoms. CONCLUSIONS: The 2 major types of lacrimal system concretions differ in
      their primary location and histopathologic composition. Further characterization
      may lead to an understanding of the mechanisms for their formation. Mucopeptide
      concretion is more appropriate than terms such as "dacryolith" and "mucolith,"
      and bacterial concretion is a more appropriate term than "canaliculith," because
      of the absence of significant calcium or stone-like density in these masses.

PMID- 22410661
TI  - Outcomes of lower eyelid cicatricial entropion with grey-line split, retractor
      recession, lateral-horn lysis, and anterior lamella repositioning.
AB  - PURPOSE: To report indications and outcomes of a technique for the correction of
      lower eyelid cicatricial entropion using a lower eyelid gray-line split, inferior
      retractor recession, lateral-horn lysis, and anterior lamella repositioning.
      PATIENTS AND METHODS: Retrospective, 5-year, single-center, consecutive case
      series of patients with lower eyelid cicatricial margin entropion undergoing the
      above procedure. Patients with significant inferior fornix contraction or
      symblepharon undergoing concurrent fornix reconstruction with buccal mucosal
      grafts at the same time as lamella repositioning were excluded. Outcomes were
      assessed based on the review of medical case notes and clinical photographs
      assessed independently. Success was defined by: 1) improvement in eyelid position
      and 2) improvement in lower eyelid retraction. RESULTS: Twenty-one eyelids of 19
      patients (mean age 57.7 +/- 22.6 years, range 5-95 years, 8 men and 11 women)
      were included. The mean follow up was 27.4 +/- 16.8 (range 3.2-59.6) months. The
      causes of cicatricial entropion were as follows: ocular cicatricial pemphigoid
      (6), Stevens-Johnson syndrome (3), previous eyelid reconstruction (2), socket
      scarring (2), thermal burn (1), chemical burn (3), postradiotherapy (1), and
      meibomian gland dysfunction (1). A second procedure was carried out in 38% (8/21)
      of eyelids within 1 year. Within 3 years, 10% (2/21) and 5% (1/21) of eyelids
      required a third and fourth procedure, respectively. The most common lower eyelid
      revision procedures included anterior lamellar repositioning. Other procedures
      required included buccal mucous membrane grafts, everting sutures, and lateral
      tarsorrhaphy. Three patients with loss of >50% inferior fornix depth were
      included. Two had previously undergone mucosal grafts and 2 required subsequent
      mucosal grafts. Overall, 90% (19/21) of eyelids eventually achieved improvement
      in lower eyelid position following repeat surgery, including mucosal grafts in 3
      eyelids. Mid-pupil lower eyelid elevation was 1 mm in 6 of 19 (32%) patients and
      lower eyelid lateral retraction significantly improved in 9 of 19 (47%) patients.
      CONCLUSION: Based on the principles of lamella repositioning and posterior middle
      lamella release with formal retractor recession through a gray-line incision,
      this technique is of value as a lash-preserving procedure in moderate-to-severe
      cicatricial lower eyelid entropion, particularly where tarsoconjuctival
      contraction or eyelid margin distortion exists.

PMID- 22410662
TI  - Transcutaneous medial canthal tendon incision to the medial orbit.
AB  - PURPOSE: The surgical approach to the medial orbit allows superior exposure of
      the medial orbital wall and nasal bones, extending to the orbital apex, with
      excellent cosmetic results. METHODS: This is a retrospective database study of
      all patients (N = 98) undergoing a transcutaneous medial canthal tendon incision
      in practice during 2009. This 1.5- to 2.0-cm incision is made just anterior to,
      in the same plane as, and shaving the anterior ramus of the medial canthal
      tendon. After exposing the origin of the anterior ramus of the medial canthal
      tendon, the periorbita along with the attached medial canthal tendon is elevated,
      exposing the entire medial orbital wall from the orbital strut to the trochlea.
      Anterior dissection allows access to the nasal bones to the dorsum of the nasal
      bridge. The parameters studied in this report were the complication rates
      (including scarring requiring revision, telecanthus, diplopia related to the
      technique, and injury to the optic nerve or other orbital structures) and
      photographic evidence of the final cosmetic result of this approach. RESULTS:
      During 2009, 173 surgical procedures were performed through the transcutaneous
      medial canthal tendon incision. The procedures comprised 89 fracture repairs of
      the nasal or ethmoid complex, 2 naso-orbito-ethmoid fracture repairs, 4 cases of
      isolated nasal fracture repair, 37 medial wall decompressions for ophthalmic
      Graves disease, 13 cases of subperiosteal abscess drainage, and 28
      dacyrocystorhinostomies using a slightly modified incisional position. The
      inferior oblique was not cut or released in any of these cases. There were no
      observed cases of medial canthal webbing, injury to orbital structures,
      telecanthus, optic neuropathy, or iatrogenically induced diplopia related to the
      technique. By definition, the authors' follow-up time is limited to less than 2
      years in each case; however, all complications, which the authors have considered
      for this report, would have been readily observable in this postoperative period.
      CONCLUSIONS: The small incision, transcutaneous medial canthal approach offers
      excellent and safe exposure of the medial wall, nose, and the orbital apex. The
      authors differentiate this transcutaneous medial canthal tendon incision from the
      less cosmetically acceptable, larger and more anterior Lynch incision. This
      medial canthal tendon incision has, and continues to be, a workhorse in the
      authors' approach to the medial orbit and nose while offering unparalleled
      exposure with an excellent safety and complication profile.

PMID- 22410663
TI  - Horner's muscle contribution to lacrimal sac drainage.
AB  - PURPOSE: This study was designed to examine the anatomical relationship between
      Horner's muscle and the lacrimal sac at 3 representative levels of the lacrimal
      sac and to verify the contribution of Horner's muscle to lacrimal sac drainage.
      METHODS: Seven ocular specimens from 7 elderly Japanese cadavers, fixed in 10%
      buffered formalin, were analyzed. Axial sections were made parallel to the eyelid
      margin at 1 mm above the upper eyelid margin, 1 mm below the lower eyelid margin,
      and 3 mm below the lower eyelid margin. The vertical common fascial length,
      length of the lateral lacrimal sac wall, and the proportion between the 2 were
      measured for each specimen at the 3 levels. RESULTS: The vertical common fascial
      length and its proportion to the length of the lateral lacrimal sac wall were
      statistically the same at all 3 levels of the lacrimal sac. CONCLUSIONS: Based on
      the present anatomical findings, the activity of Horner's muscle may be the same
      for all sac levels, although this hypothesis should be examined by further
      experimental research, such as manometric studies of the sac at different levels
      along its length.

PMID- 22410664
TI  - Cadaveric anatomical comparison of the lateral nasal wall after external and
      endonasal dacryocystorhinostomy.
AB  - PURPOSE: Much literature has accumulated espousing the relative merits of
      endonasal and external dacryocystorhinostomy (DCR). However, there is
      comparatively little information on the relative anatomic differences between
      these 2 approaches. The purpose of this study is to investigate the anatomic
      relationships of the lateral nasal wall for endonasal and external DCR. METHODS:
      Ten cadaver half heads were used in this study. Half were subject to endonasal
      and half to external DCR procedures. The lateral nasal wall was then dissected
      and measurements were taken of ostium and anastomosis size and position relative
      to other landmarks on the lateral nasal wall. Relationships were compared between
      the 2 procedures. RESULTS: The dimensions and area of the ostium and the
      anastomosis were similar between the 2 procedures. The lower portion of the
      ostium was located more inferiorly in endonasal DCR. Additionally, the ostium was
      more likely to be found lateral to the axilla of the middle turbinate in
      endonasal DCR, when compared with anterior for external. External DCR was also
      more likely to involve opening the anterior ethmoid air cells than endonasal
      approach. CONCLUSION: Endonasal and external DCR osteomies appear to be of
      similar size, with the endonasal opening being located slightly lower and more
      posterior on the lateral nasal wall.

PMID- 22410665
TI  - Re:  "ocular damage secondary to intense pulse light therapy to the face".

PMID- 22410669
TI  - Re: "Mueller's muscle-conjunctival resection in the treatment of congenital
      ptosis".

PMID- 22410667
TI  - Re:  "the patient with an ocular prosthesis and his mirror image".

PMID- 22410670
TI  - Guarded suction monopolar cautery for endoscopic dacryocystorhinostomy.

PMID- 22410671
TI  - Curcumin inhibits LPS-induced CCL2 expression via JNK pathway in C6 rat
      astrocytoma cells.
AB  - The important role of neuroinflammation in many chronic and acute pathological
      conditions of the central nervous system is widely recognized. Curcumin is a
      major component of turmeric and reportedly has anti-inflammatory and anti-oxidant
      effects. This study investigated the inhibitory effect of curcumin on
      lipopolysacharide (LPS)-induced chemokine CCL2 (or monocyte chemoattractant
      protein-1, MCP-1) production and whether the effect is mediated by mitogen
      activated protein kinases (MAPKs) in the rat astrocytoma cell C6. We observed
      that LPS (1 MUg/ml) induced the upregulation of CCL2 mRNA and protein in C6.
      Treatment with curcumin (2.5, 10, and 25 MUM) decreased the expression of CCL2
      mRNA and protein in a dose-dependent manner under treatment with LPS.
      Additionally, the c-jun N-terminal kinase (JNK) inhibitor (SP600125) dose
      dependently inhibited LPS-induced CCL2 upregulation, whereas the MAPK kinase
      (MEK) inhibitor (PD98059) only had a mild effect and the p38 MAPK inhibitor
      (SB203580) had no effect. Finally, western blot showed that LPS induced rapid JNK
      activation and curcumin reduced LPS-induced phosphoJNK (pJNK) expression at 30
      min after LPS stimulation. These data suggest that the anti-neuroinflammatory
      effect of curcumin relates to the downregulation of CCL2 expression through the
      JNK pathway in astrocytoma cells, which indicates a possible benefit from the use
      of curcumin in the treatment of neuroinflammation-associated disorders.

PMID- 22410672
TI  - Down regulation of the proliferation and apoptotic pathways in the embryonic
      brain of diabetic rats.
AB  - Compelling evidence shows that the offspring subjected to uncontrolled
      hyperlycemia during gestation display behavioral, neurochemical, and cellular
      abnormalities during adulthood. However, the molecular mechanisms underlying
      these defects remain elusive. Previous studies have shown an increased rate of
      apoptosis and a decreased index of neuronal proliferation associated with
      diabetic embryopathy. The aim of the present study was to determine whether
      impairments in apoptotic related proteins also occur in the developing central
      nervous system from non-malformed embryos exposed to uncontrolled gestational
      hyperglycemia. Pregnant rats injected with either streptozotocin or vehicle were
      killed on gestational day 19. Offspring brains were quickly removed to evaluate
      protein expression by Western blotting. Embryonic brains from diabetic rats
      exhibited a decrease in the cell survival p-Akt expression (52.83 +/- 24.35%) and
      in the pro-apoptotic protein Bax (56.16 +/- 6.47%). Moreover, the anti-apoptotic
      protein Bcl-2 showed a non-significant increase while there were no changes in
      Procaspase 3 or cleaved Caspase 3 proteins. The cytoskeleton proteins NF-200 and
      GFAP were also examined. Neither NF-200 nor GFAP showed differences in embryonic
      brains from diabetic rats compared to controls. Altogether, these results
      indicate that both proliferation and apoptotic pathways are decreased in the
      brain from the developing offspring of diabetic rats. Since selective neuronal
      apoptosis, as well as selective cell proliferation, are specifically involved in
      brain organogenesis, it is possible that simultaneous impairments during the
      perinatal period contribute to the long lasting alterations observed in the adult
      brain.

PMID- 22410673
TI  - Relative expression of type II MAGE genes during retinoic acid-induced neural
      differentiation of mouse embryonic carcinoma P19 cells: a comparative real-time
      PCR analysis.
AB  - In mammals, the type II melanoma antigen (MAGE) protein family is constituted by
      at least ten closely related members, but our understanding of their function in
      the developing nervous system remains poor. To systematically study the
      expression pattern of type II MAGE genes during neurogenesis, we employed mouse
      embryonic carcinoma P19 cells as an in vitro model for neural differentiation by
      retinoic acid (RA) induction. The expression of type II MAGE genes was
      investigated under distinct steps of differentiation by a comparative DeltaDeltaC
      (T) paradigm of real-time quantitative reverse-transcription PCR (qRT-PCR). The
      relative levels of each gene expression at various steps of differentiation were
      expressed as a fold change compared with that in RA-untreated P19 cells. The
      results revealed that: (1) the expression of MAGE-E1, E2, and Necdin transcripts
      was steadily increased, and the relative levels of MAGE-D1, D2, D3, F1, G1, and
      H1 mRNA were fluctuantly elevated after the RA-treatment at embryoid body and
      neural stages; (2) during RA-treatment and subsequent differentiation, the
      expression of MAGE-L2 mRNA was decreased. Therefore, our results suggested that
      MAGE-D1, D2, D3, E1, E2, F1, G1, H1, and Necdin might be involved in the early
      process of neurogenesis, and MAGE-L2 connected with maintenance of pluripotency
      of stem cells. These studies may present some clues for a better understanding of
      the fundamental aspects of type II MAGE genes during neurogenesis.

PMID- 22410674
TI  - Nickel-catalyzed [4+2] cycloaddition for highly substituted arenes.
AB  - Nickel(0) catalyzed [4+2] cycloaddition of electron-deficient dienes to alkynes
      and subsequent aromatization gave highly substituted arenes. This formal inverse
      electron-demand Diels-Alder cycloaddition is attributed to the formation of a
      seven-membered nickelacycle from a diene and an alkyne.

PMID- 22410677
TI  - Infection: high-dose antiviral therapy does not prevent short episodes of HSV-2
      reactivation.

PMID- 22410675
TI  - The role of prostanoids in urinary bladder physiology.
AB  - Five primary prostanoids are synthesized by the cyclooxygenase enzymes, COX-1 and
      COX-2: the prostaglandins PGE(2), PGF(2alpha), PGI(2), PGD(2) and thromboxane A2.
      High levels of these signaling molecules have been implicated--in both animal
      models and human studies--in decreased functional bladder capacity and
      micturition volume and increased voiding contraction amplitude. Thus, inhibition
      of prostanoid production or the use of prostanoid receptor antagonists, might be
      a rational way to treat patients with detrusor muscle overactivity. Similarly,
      prostanoid receptor agonists, or agents that stimulate their production, might
      have a function in treating bladder underactivity. Although some promising
      results have been reported, the adverse effects of nonselective cyclooxygenase
      inhibitors are a major concern that restricts their use in the treatment of
      functional bladder disorders. Further preclinical and clinical studies are needed
      before cyclooxygenase inhibitors, prostanoid receptor agonists and antagonists
      become worthwhile therapeutic tools in this setting.

PMID- 22410678
TI  - Prostate cancer: modeling the outcomes of prostate cancer screening.

PMID- 22410681
TI  - Pediatrics: evaluation and management of gender identity disorder--an American
      tale.

PMID- 22410683
TI  - Sexual dysfunction: a new tool for early identification of penile endothelial
      dysfunction.

PMID- 22410682
TI  - CT urography for hematuria.
AB  - Hematuria can signify serious disease such as bladder cancer, upper urinary tract
      urothelial cell carcinoma (UUT-UCC), renal cell cancer or urinary tract stones.
      CT urography is a rapidly evolving technique made possible by recent advances in
      CT technology. CT urography is defined as CT examination of the kidneys, ureters
      and bladder with at least one series of images acquired during the excretory
      phase after intravenous contrast administration. The reasoning for using CT
      urography to investigate hematuria is based on its high diagnostic accuracy for
      urothelial cell carcinoma (UCC) and favorable comparison with other imaging
      techniques. The optimum diagnostic imaging strategy for patients with hematuria
      at high-risk for UCC involves the use of CT urography as a replacement for other
      imaging tests (ultrasonography, intravenous urography, or retrograde
      ureteropyelography) and as a triage test for cystoscopy, resulting in earlier
      diagnosis and improved prognosis of bladder cancer, UUT-UCC, renal cell cancer
      and stones. Current problems with CT urography for investigating hematuria might
      be solved with a formative educational program simulating clinical reporting to
      reduce reader error, and a new technique for image-guided biopsy of UUT-UCC
      detected by CT urography for histopathological confirmation of diagnosis and
      elimination of false-positive results. CT urography is recommended as the initial
      imaging test for hematuria in patients at high-risk for UCC.

PMID- 22410687
TI  - A literature review of reporting standards of HIV progression models.
AB  - OBJECTIVE: We conducted a systematic review of HIV progression models to identify
      the mathematical structures used, the main research questions and key model
      aspects in terms of quality and robustness. METHODS: We searched for articles
      published before February 2009 that described models of HIV progression in
      humans. We included two strategies of search with and without MeSH terms. We
      classified the models by their mathematical structure and research question. We
      created a checklist of desirable features of the models, reviewed and classified
      the articles to inform our conclusions. RESULTS: Among 3491 articles found, 93
      met the inclusion criteria. Among the selected articles, 60 used transition
      models, 25 applied differential equations, and eight had other structures. We did
      not find a relation between the type of question explored and the modeling method
      used. None of the studies complied with the complete set of items in the
      checklist, but 6.5% cover at least 90% of them. CONCLUSION: There is an enormous
      heterogeneity of HIV modeling exercises in terms of methods used and topics
      addressed, as well as in the presentation of key aspects of the articles in terms
      of quality and robustness.

PMID- 22410688
TI  - Ferromagnetic Mn-doped Si0.3Ge0.7 nanodots self-assembled on Si(100).
AB  - Densely packed epitaxial Mn-doped Si(0.3)Ge(0.7) nanodots self-assembled on
      Si(100) have been obtained. Their structural properties were studied using
      reflection high-energy electron diffraction, energy dispersive x-ray diffraction,
      atomic force microscopy, extended x-ray absorption fine structure measurements
      and high-resolution transmission electron microscopy. Mn(5)Ge(1)Si(2)
      crystallites embedded in Si(0.3)Ge(0.7) were found. They exhibit a ferromagnetic
      behaviour with a Curie temperature of about 225 K.

PMID- 22410692
TI  - Pearls and pitfalls:  everyone needs iron.

PMID- 22410694
TI  - Is the pill the answer for patients with the female athlete triad?

PMID- 22410685
TI  - Differences in the causes of death of HIV-positive patients in a cohort study by
      data sources and coding algorithms.
AB  - OBJECTIVES: To compare causes of death (CoDs) from two independent sources:
      National Basic Death File (NBDF) and deaths reported to the Spanish HIV Research
      cohort [Cohort de adultos con infeccion por VIH de la Red de Investigacion en
      SIDA CoRIS)] and compare the two coding algorithms: International Classification
      of Diseases, 10th revision (ICD-10) and revised version of Coding Causes of Death
      in HIV (revised CoDe). METHODS: Between 2004 and 2008, CoDs were obtained from
      the cohort records (free text, multiple causes) and also from NBDF (ICD-10). CoDs
      from CoRIS were coded according to ICD-10 and revised CoDe by a panel. Deaths
      were compared by 13 disease groups: HIV/AIDS, liver diseases, malignancies,
      infections, cardiovascular, blood disorders, pulmonary, central nervous system,
      drug use, external, suicide, other causes and ill defined. RESULTS: There were
      160 deaths. Concordance for the 13 groups was observed in 111 (69%) cases for the
      two sources and in 115 (72%) cases for the two coding algorithms. According to
      revised CoDe, the commonest CoDs were HIV/AIDS (53%), non-AIDS malignancies (11%)
      and liver related (9%), these percentages were similar, 57, 10 and 8%,
      respectively, for NBDF (coded as ICD-10). When using ICD-10 to code deaths in
      CoRIS, wherein HIV infection was known in everyone, the proportion of non-AIDS
      malignancies was 13%, liver-related accounted for 3%, while HIV/AIDS reached 70%
      due to liver-related, infections and ill-defined causes being coded as HIV/AIDS.
      CONCLUSION: There is substantial variation in CoDs in HIV-infected persons
      according to sources and algorithms. ICD-10 in patients known to be HIV-positive
      overestimates HIV/AIDS-related deaths at the expense of underestimating liver
      related diseases, infections and ill defined causes. CoDe seems as the best
      option for cohort studies.

PMID- 22410695
TI  - Return to collision sport after pneumomediastinum.

PMID- 22410696
TI  - Cardiac noncompaction:  a rare cause of exertional syncope in an athlete.

PMID- 22410698
TI  - Cardiac auscultation in sports medicine:  strategies to improve clinical care.
AB  - Cardiac auscultation is an important part of the preparticipation physical
      examination of athletes. Sudden death remains a rare but tragic event among
      athletes. The most common cause of sudden death among young athletes in the
      United States continues to be hypertrophic cardiomyopathy, which may or may not
      present with a typical heart murmur. Many clinicians do not possess sufficient
      proficiency in recognizing abnormal heart murmurs. New insights in the field of
      auditory learning suggest that cardiac auscultation is more of a technical skill
      than an intellectual one. Intensive repetition of abnormal heart murmurs has been
      shown to improve proficiency in cardiac auscultation markedly. Sample audio files
      of two important murmurs, i.e., an innocent murmur and hypertrophic
      cardiomyopathy, are provided online with this review.

PMID- 22410697
TI  - Cardiac electrophysiology and the athlete:  a primer for the sports clinician.
AB  - Intense exercise requires a significant increase in cardiac output in order to
      meet the needs of the skeletal muscles for oxygenated blood. In order to improve
      cardiac performance, the autonomic nervous system increases sympathetic tone
      primarily through release of norepinephrine from postganglionic receptors to
      stimulate the beta-adrenergic receptors of the nodal and muscle tissue of the
      heart. This event initiates a signaling cascade focused on increasing the amount
      of calcium available to the contractile myofilaments in the cardiac cell. Failure
      of the myocytes to counterbalance the increase in inward ion flow or adequately
      sequester cytosolic calcium during diastole leads to potentially catastrophic
      electrical instability. In this review, the relationship between the cellular
      events initiated by exercise and the induction of arrhythmias associated with the
      long QT, Brugada, and Wolff-Parkinson-White syndromes; catecholaminergic
      polymorphic ventricular tachycardia; and the heritable cardiomyopathies are
      explored.

PMID- 22410699
TI  - Wheezing after respiratory tract infection in athletes.
AB  - Wheezing is a commonly encountered complaint by patients seen in sports medicine
      practice. Wheezes are a continuous musical sound heard best on expiration and can
      originate from one or more of several defined anatomical locations in the human
      airway. While common causes of wheezing include exercise-induced
      bronchoconstriction, postnasal drip, and asthma, wheezing also follows specific
      respiratory infections and can persist for months after the onset of symptoms.
      Abnormal lung physiology following pneumonia can persist for decades. These
      postinfectious pulmonary changes affect the ability of athletes to return to
      sports. In addition to history and physical examination, diagnosis may require
      pulmonary function testing and exercise challenge testing. The cornerstone to
      management is an accurate diagnosis and using lifestyle and pharmacologic
      intervention. Return to play should be gradual and allowed only after individuals
      demonstrate adequate pulmonary capacity to meet the demands of their sport.
      Providers also should be aware of governing body regulations regarding treatments
      and required therapeutic use exemptions.

PMID- 22410700
TI  - An abdominal cause of lower extremity pain in a young soccer player.

PMID- 22410701
TI  - Testicular conditions in athletes:  torsion, tumors, and epididymitis.
AB  - Individuals involved in sports are at risk for sustaining various injuries. In
      addition to musculoskeletal complaints, male athletes are at risk of incurring
      testicular injuries. These issues can range from an acute emergency such as
      testicular torsion to indolent testicular tumors. In contrast, epididymitis can
      present in stages. Presentation and management of testicular complaints can vary
      depending on the condition. Physicians who provide medical care to athletes need
      to be competent in diagnosing and managing testicular injuries.

PMID- 22410702
TI  - Osteitis pubis in athletes.
AB  - Osteitis pubis is one of many etiologies of groin pain in athletes. It is a
      painful overuse injury of the pubic symphysis and the parasymphyseal bone that
      typically is found in athletes whose sports involve kicking, rapid accelerations,
      decelerations, and abrupt directional changes. Athletes most commonly present
      with a complaint of anterior and/or medial groin pain but also can present with
      lower abdominal, adductor, inguinal, perineal, and/or scrotal pain. Symptoms can
      be severe and can limit participation in sport until treatment is instituted.
      Imaging is useful for ruling out other etiologies of groin pain, identifying
      concomitant pathology, and confirming the diagnosis itself. Treatment is varied
      but usually includes nonoperative measures of rest, rehabilitation, and/or
      pharmacotherapy and also may include injections and/or surgical procedures. A
      high clinical suspicion should exist when evaluating soccer, rugby, or American
      football players and distance runners who present with complaints of groin pain.

PMID- 22410703
TI  - Upper gastrointestinal issues in athletes.
AB  - Gastrointestinal (GI) complaints are common among athletes with rates in the
      range of 30% to 70%. Both the intensity of sport and the type of sporting
      activity have been shown to be contributing factors in the development of GI
      symptoms. Three important factors have been postulated as contributing to the
      pathophysiology of GI complaints in athletes: mechanical forces, altered GI blood
      flow, and neuroendocrine changes. As a result of those factors, gastroesophageal
      reflux disease (GERD), nausea, vomiting, gastritis, peptic ulcers, GI bleeding,
      or exercise-related transient abdominal pain (ETAP) may develop. GERD may be
      treated with changes in eating habits, lifestyle modifications, and training
      modifications. Nausea and vomiting may respond to simple training modifications,
      including no solid food 3 hours prior to an athletic event. Mechanical trauma,
      decreased splanchnic blood flow during exercise, and non-steroidal anti
      inflammatory drugs (NSAID) contribute to gastritis, GI bleeding, and ulcer
      formation in athletes. Acid suppression with proton-pump inhibitors may be useful
      in athletes with persistence of any of the above symptoms. ETAP is a common,
      poorly-understood, self-limited acute abdominal pain which is difficult to treat.
      ETAP incidence increases in athletes beginning a new exercise program or
      increasing the intensity of their current exercise program. ETAP may respond to
      changes in breathing patterns or may resolve simply with continued training.
      Evaluation of the athlete with upper GI symptoms requires a thorough history, a
      detailed training log, a focused physical examination aimed at ruling out
      potentially serious causes of symptoms, and follow-up laboratory testing based on
      concerning physical examination findings.

PMID- 22410704
TI  - IDH mutations as an early and consistent marker in low-grade astrocytomas WHO
      grade II and their consecutive secondary high-grade gliomas.
AB  - This study investigated the prognostic and predictive significance of IDH1 and
      IDH2 mutations in low-grade astrocytomas (LGA). The presence and consistency of
      IDH mutations during the progression of LGA to secondary high-grade gliomas
      (sHGG) were detected. Samples of patients with LGA and sHGG were investigated.
      The genomic regions around IDH1 codon 132 and IDH2 codon 172 were PCR amplified
      and directly sequenced. Furthermore, the MGMT promoter status was provided using
      the methylation-specific PCR. Our population comprised 71 patients with a total
      of 45 pairs of LGA and their consecutive sHGG. Median follow-up was 9.6 years.
      IDH mutations were found in 36/45 LGA (80%) and their sHGG without changes in the
      mutation status. A total of 71 patients with LGA were analyzed according to
      clinical and molecular tumor-related factors: 56/71 patients (78.8%) had an IDH
      mutation without significant influence on the progression-free or overall
      survival (OS), and 22/71 (31%) of the patients received postoperative
      radiotherapy (RT) after diagnosis of LGA. Patients with early RT but without IDH
      mutations had the shortest survival. Our study shows that IDH mutation status is
      stable during the progression course of LGA to sHGG. The presence of IDH
      mutations fails to demonstrate a significant influence on survival in the
      multivariate analysis of LGA patients. Early RT appears to be beneficial only LGA
      patients with IDH-mutations.

PMID- 22410705
TI  - Tuberculosis seasonality in the Netherlands differs between natives and non
      natives: a role for vitamin D deficiency?
AB  - SETTING: The seasonality of tuberculosis (TB) incidence suggests that the risk of
      infection or development of disease has a seasonal component. OBJECTIVE: To
      investigate factors associated with seasonal patterns of TB disease in the
      Netherlands by splitting notifications according  to origin (natives vs. non
      natives) and disease site (pulmonary TB [PTB] vs. extra-pulmonary TB [EPTB]). We
      focus on the presence of a seasonal peak, as much debate has centred on factors
      enhancing transmission vs. disease development. DESIGN: Monthly notifications
      were derived from culture  sample dates of all cases between 1993 and 2008. We
      fitted seasonal autoregressive integrated moving average (SARIMA) models to the
      time series. Seasonal decomposition revealed seasonal trends. To assess the
      seasonality of the peak, we repeated the analysis omitting December (trough)
      notifications. RESULTS: TB notifications show a seasonal pattern, with a peak in
      spring and a trough in winter, which is present in both PTB and EPTB and in both
      natives and non-natives. However, when excluding December notifications,
      seasonality only holds in non-native EPTB and non-native TB notifications.
      CONCLUSION: A seasonal peak in TB notifications (March-June) is apparent in non
      natives, but is absent in natives. This peak is driven by the seasonality of EPTB
      notifications, which are highest in June-July. The contribution of winter
      crowding is discussed. Vitamin D deficiency, enhancing  disease development at
      the end of winter-early spring, seems the most likely factor explaining the
      yearly peak in EPTB.

PMID- 22410706
TI  - [Current indications for triple therapy in hepatitis C virus infection].
AB  - Chronic hepatitis C virus (HCV) infection is the main cause of liver cirrhosis
      and liver carcinoma in western countries. There is evidence that HCV clearance
      induced by antiviral therapy is beneficial, increasing survival and reducing the
      complications of cirrhosis. Triple therapy with boceprevir or telaprevir
      associated with pegylated interferon and ribavirin has increased rates of
      sustained viral response both in treatment-naive patients and in those failing
      previous regimens. Before treating patients with these new molecules, physicians
      should be familiar with their indications and the regimens to be used.
      Furthermore, both adverse events and the development of resistances must be
      monitored. The main aims are careful selection of patients and of the regimen to
      be used, and achieving adequate adherence to obtain optimal results.

PMID- 22410707
TI  - Phosphate starvation as an antimicrobial strategy: the controllable toxicity of
      lanthanum oxide nanoparticles.
AB  - Lanthanum oxide nanoparticles were utilized to scavenge phosphate from microbial
      growth media for the use of targeted nutrient starvation as an antimicrobial
      strategy. Only in phosphate poor environments a toxic effect was observed. The
      effect was shown on Escherichia coli, Staphylococcus carnosus, Penicillium
      roqueforti, and Chlorella vulgaris.

PMID- 22410708
TI  - Current treatment considerations in metastatic renal cell carcinoma.
AB  - OPINION STATEMENT: In general, debulking neprhectomy is still considered for
      metastatic RCC patients with primary tumor in place, assuming good performance
      status. Initial systemic therapy should consider high-dose IL-2 for the highly
      select patient. One reason for initial consideration of this therapy is the less
      certain risk/benefit profile if employed after targeted therapy. Notably, due to
      its potential toxicity and emergence of new effective and more tolerable drugs,
      IL-2 has become a less favorable and subsequently a less utilized therapeutic
      tool in the current era. Otherwise, VEGF-targeted therapy is the treatment of
      choice, preferably on a clinical trial. Off trial, sunitinib has long been
      favored but pazopanib is gaining more use for tolerance pending the comparative
      trial. Continued VEGF targeting is favored by these authors given the underlying
      biology of RCC and the prospective clinical data, noting no direct comparison of
      mTOR and VEGF agents has yet occurred. Maintaining patient dose is critical and
      requires optimal supportive care and appreciation/early intervention for
      toxicity. Predictive biomarkers are desperately needed, and enrollment on
      clinical trials remains a priority to optimize patient outcome.

PMID- 22410709
TI  - The adjuvant treatment of HER2-positive breast cancer.
AB  - OPINION STATEMENT: About 15-20% of patients with early stage breast cancer
      present with tumors that have overexpression or amplification of the human
      epidermal growth factor receptor 2 (HER2) gene. Before 2005, these individuals
      had an increased risk of recurrence and death, but since then their outcomes have
      substantially improved with the adoption in most countries of adjuvant
      trastuzumab as a standard component of therapy for HER2-positive early-stage
      breast cancer. Consequently, access to high-quality and accurate HER2 testing
      methods is critical to accurately determine HER2 status, guide treatment
      decisions, and ultimately improve clinical outcomes. In 2012, the humanized
      monoclonal anti-HER antibody trastuzumab was the only approved HER2-targeted
      therapy in the adjuvant setting. Data from the first generation of trials
      combining it with various chemotherapy regimens showed significant improvements
      in disease-free and overall survival (DFS/OS). Based on results from five
      randomized clinical trials, a trastuzumab-containing regimen for up to 1 year is
      now considered standard for all patients with HER2-positive tumors larger than 1
      cm in size who would have fulfilled eligibility to those studies, and this
      recommendation is sometimes extended to patients with stage I tumors greater than
      0.5 cm (T1b). Second generation adjuvant studies with other HER2-targeted agents
      like lapatinib and pertuzumab are ongoing, and newer drugs like T-DM1 and
      neratinib are being actively tested in the metastatic setting.

PMID- 22410710
TI  - Preliminary lessons learned from the "Native Navigators and the Cancer Continuum"
      (NNACC).
AB  - This community-based participatory research (CBPR) study was based on patient
      navigation (Navigator) among three original sites: Colorado, Michigan, and South
      Dakota. During 2010, the study added two sites: the Comanche Nation and the
      Muscogee (Creek) Nation (Oklahoma). The intervention includes 24-h of a Navigator
      implemented cancer education program that addresses the full continuum of cancer
      care. The partners include agreements with up to two local Native American
      organizations each year, called Memorandum Native Organizations, who have strong
      relationships with local American Indians. Family fun events are used to initiate
      the series of workshops and to collect baseline data and also to wrap up and
      evaluate the series 3 months following the completion of the workshop series.
      Evaluation data are collected using an audience response system (ARS) and stored
      using an online evaluation program. Among the lessons learned to date are: the
      Institutional Review Board processes required both regional and national
      approvals and took more than 9 months. All of the workshop slides were missing
      some components and needed refinements. The specifics for the Memorandum Native
      Organization deliverables needed more details. The ARS required additional
      training sessions, but once learned the Navigator use the ARS well. Use of the
      NACR website for a password-protected page to store all NNACC workshop and
      training materials was easier to manage than use of other online storage
      programs. The community interest in taking part in the workshops was greater than
      what was anticipated. All of the Navigators' skills are improving and all are
      enjoying working with the community.

PMID- 22410711
TI  - Many faces of angioedema:  focus on the diagnosis and management of abdominal
      manifestations of hereditary angioedema.
AB  - Angioedema of the intestinal tract is an infrequent but well-described cause of
      abdominal pain that can occur because of inherited, acquired, allergic, or drug
      induced causes. Hereditary angioedema (HAE) is a genetic disorder that causes
      recurrent attacks of severe edema of various body parts, including the intestinal
      tract. Moderate to severe abdominal pain occurs in 43-93% of such attacks due to
      intestinal edema. Laryngeal edema is a potentially life-threatening
      manifestation. Failure to recognize and diagnose HAE or other causes of
      intestinal angioedema can lead to years of delay in diagnosis, and in the case of
      HAE, often to unnecessary abdominal surgeries. Recognizing the typical history of
      recurrent attacks of abdominal pain, oropharyngeal/laryngeal angioedema or
      cutaneous angioedema, family history of similar symptoms, association of attacks
      with stress or menses, and exacerbation of attacks after administration of
      estrogens or angiotensin-converting enzyme inhibitors will increase diagnostic
      accuracy. Interdisciplinary treatment is often necessary after the diagnosis of
      HAE, first with acute management in the emergency room or the intensive care
      unit, followed by either drug prophylaxis against future attacks using a C1
      esterase inhibitor concentrate or attenuated androgens and discontinuation of
      medications known to trigger attacks. Newer drugs approved for treatment of acute
      attacks may have future roles in the prevention of attacks if further studies
      support their efficacy. Gastroenterologists in particular should maintain a high
      index of suspicion for the possibility of HAE or other causes of intestinal
      angioedema in patients with a history of recurrent abdominal pain.

PMID- 22410712
TI  - Recurrence after surgical resection of gastrinoma:  who, when, where and why?
AB  - BACKGROUND: Surgery prolongs survival in patients with gastrinomas, but
      postoperative recurrences are frequent and controversies still exist about the
      optimal surgical procedures. AIM: The aim of this study is to analyze biological
      and morphological recurrences and to search for risk factors. PATIENTS AND
      METHODS: Between 1990 and 2008, 22 patients (five with multiple endocrine
      neoplasia type 1) who underwent curative resection for gastrinoma were evaluated
      every 6 months for biological and morphological recurrences. All patients were
      disease-free postresection. RESULTS: The median postoperative follow-up was 37
      months (range, 7-204 months). A biological recurrence was observed in 59% of
      cases, after a median time of 16.5 months (range, 7-90 months). A morphological
      recurrence was reported in 32% of cases, in the liver (86%) or lymph nodes (43%),
      after a median time of 21 months (range, 8-91 months). The median delay between
      biological and morphological recurrence was 3 months (range, 0-69 months). At
      recurrence, all patients were offered a second treatment (surgical resection in
      71% of cases). One and 5 year overall survival were 100 and 76%, respectively.
      One and 5 year biological disease-free survival (DFS) were 76 and 27%,
      respectively. One and 5 year morphological DFS were 90 and 62%, respectively.
      Tumor size of at least 20 mm (P=0.008) and pancreatic location (P=0.04) of the
      primary tumor had significant effect on morphological DFS. Overall survival was
      significantly lower in patients with primary tumor of at least 20 mm (P=0.01).
      CONCLUSION: (a) Recurrence occurs in nearly two out of three patients operated
      upon for gastrinoma, most often detected through biological tests; (b) lymph
      nodes and liver are the most frequent sites of relapse and patients benefit from
      second treatment; (c) risk factors for recurrences are as follows: size of at
      least 20 mm; and the pancreatic location of the primary tumor.

PMID- 22410713
TI  - Meta-analysis of observational studies on cholecystectomy and the risk of
      colorectal adenoma.
AB  - AIM: Cholecystectomy has been suggested as a risk factor for colorectal cancer.
      However, the association of cholecystectomy and the risk of colorectal adenoma
      (CRA) remains unclear. We conducted a meta-analysis of observational studies to
      explore this relationship. METHODS: We identified studies by a literature search
      of MEDLINE and EMBASE through 30 September 2011, and by searching the reference
      lists of pertinent articles. Summary relative risks (SRRs) with their 95%
      confidence intervals (CIs) were calculated with a random-effects model. Between
      study heterogeneity was assessed using Cochran's Q statistic and the I2. RESULTS:
      A total of 10 studies (including 4061 CRA cases) were included in this meta
      analysis. Analysis of these 10 studies found that no effect of cholecystectomy on
      the risk of CRAs was shown (SRR, 1.17; 95% CI: 0.93-1.48), with no significant
      heterogeneity among these studies (P heterogeneity=0.106, I2=37.9%). This null
      association was seen in both men and women (men: SRR=1.00, 95% CI: 0.58-1.73;
      women: SRR=1.39, 95% CI: 0.95-2.04). CONCLUSION: The results of this meta
      analysis suggest that there is no positive association between previous
      cholecystectomy and the risk of CRA development in both men and women.

PMID- 22410714
TI  - Platelet count/spleen diameter ratio to predict the presence of esophageal
      varices in patients with cirrhosis:  a systematic review.
AB  - BACKGROUND: Esophageal variceal bleeding remains the leading cause of acute
      mortality in patients with cirrhosis. Platelet count to spleen diameter (PC/SD)
      ratio less than 909 is one of several parameters proposed for the noninvasive
      prediction of esophageal varices. The aim of this study is to systematically
      review the evidence on the diagnostic accuracy of the 909 ratio. METHODS: We
      identified relevant studies from a MEDLINE search and performed a meta-analysis
      to estimate the pooled sensitivity, specificity, and positive and negative
      likelihood ratios (LRs) using Meta-Disc software. RESULTS: Eight studies met the
      inclusion criteria and included a total of 1275 patients. Meta-analysis yielded a
      pooled sensitivity of 89% [95% confidence interval (CI) 87-92%; I2 statistic
      92.9%] and a pooled specificity of 74% (95% CI 70-78%; I2 statistic 94.5%). The
      pooled positive LR was 3.5 (95% CI 1.92-6.25; I2 statistic 94.0%) and the pooled
      negative LR was 0.12 (95% CI 0.05-0.32; I2 statistic 90.8%). The quality of the
      evidence as assessed by the GRADE methodology was low. CONCLUSION: In its present
      form, the test characteristics of PC/SD ratio of 909 may not be adequate to
      completely replace esophagogastroduodenoscopy as a noninvasive screening tool for
      esophageal varices, given the low grade of evidence. However, it may be
      potentially useful as part of a prediction rule incorporating other clinical
      characteristics or varying PC/SD cutoffs. When compared with other noninvasive
      predictor tools, the PC/SD ratio is elegant, simple, and inexpensive. With some
      minor modifications, it may become a helpful tool to limit the number of
      endoscopies in primary prophylaxis to be performed in patients with portal
      hypertension.

PMID- 22410715
TI  - Venous thromboembolism in patients with cholangiocarcinoma:  focus on risk
      factors and impact on survival.
AB  - BACKGROUND: A high incidence of venous thromboembolism (VTE) has been observed in
      patients with cancer. However, few data are available on patients with
      cholangiocarcinoma. OBJECTIVES: The aim of this study was to evaluate the
      clinical characteristics and risk factors of VTE and to investigate whether VTE
      would affect the survival of patients with cholangiocarcinoma. METHODS: We
      retrospectively reviewed 273 patients who were diagnosed with cholangiocarcinoma
      from January 2004 to December 2008. RESULTS: We observed 40 cases of VTE, among
      which 10 patients had VTE at diagnosis. There were 14 cases of pulmonary
      thromboembolism with or without deep vein thrombosis, 18 cases of portal vein
      thrombosis, four cases of inferior vena cava thrombosis, and four of hepatic vein
      thrombosis. We found that progression of stage, C-reactive protein, and
      chemotherapy were significantly associated with the occurrence of VTE (P=0.022,
      0.006, and 0.014, respectively). The median survival in the VTE and non-VTE
      groups were 13.0 and 25.0 months, respectively (log-rank test, P=0.026). VTE was
      an unfavorable prognostic factor for cholangiocarcinoma (hazard ratio=1.626,
      P=0.042). CONCLUSION: In our study, advanced stage, C-reactive protein, and
      treatment with chemotherapeutic agents were related to the occurrence of VTE in
      patients with cholangiocarcinoma. VTE was an independent unfavorable prognostic
      factor for survivors of cholangiocarcinoma.

PMID- 22410716
TI  - A new approach to gastrointestinal fistula closure:  endoloop and clips technique
      using double endoscope.
AB  - Several endoscopic techniques have been described for closure of gastrointestinal
      fistulas. Herein, we describe a case of iatrogenic gastric fistula successfully
      treated with a new approach by simultaneous insertion of two endoscopes and using
      the endoloop and endoclips technique.

PMID- 22410717
TI  - Cadmium accumulation and strategies to avoid its toxicity in roots of the citrus
      rootstock Citrumelo.
AB  - In order to assess implications of Cd-induced oxidative stress in roots of the
      citrus rootstock Citrumelo, seedlings were hydroponically exposed to two
      relatively realistic Cd concentrations during 7 days. Our results showed that
      increasing Cd concentrations in external solution were associated with higher Cd
      accumulations in roots. At 5MUM Cd the accumulation of Cd in roots was over 70-f
      higher than in aerial part (stem+leaves). Malondialdehyde (MDA), superoxide
      radical (O(2)(*-)), hydrogen peroxide (H(2)O(2)) and lipoxygenase activity (LOX)
      increased in Cd-exposed roots, suggesting a metal-induced oxidative stress. The
      Cd treatment enhanced the activity of antioxidant enzymes superoxide dismutase
      (SOD), catalase (CAT) and guaiacol-type peroxidase (G-POD), as well as the
      content of secondary metabolites i.e. soluble phenolics (SPs) and lignin.
      Histochemical analyses of roots showed that Cd, H(2)O(2), (O(2)(*-)), lignin and
      G-POD displayed a similar location pattern. Almost all analyzed parameters showed
      a similar dynamic tendency with increases under 5MUM Cd followed by decreases
      under 10MUM Cd, suggesting that a complex coordinated Cd-defensive mechanism is
      operating in Citrumelo roots exposed to environmental realistic Cd
      concentrations.

PMID- 22410718
TI  - Polyaniline nanofibers assembled on alginate microsphere for Cu2+ and Pb2+
      uptake.
AB  - Polyaniline (PANI) nanofibers were assembled on the micro- or millimeter-scale
      calcium alginate (CA) beads by "competitive adsorption-restricted polymerization"
      approach. The CA beads made the dimensional expansion of PANI nanofibers evident,
      which overcame the serious aggregation of PANI nanofibers and benefited the
      practical operation of PANI nanofibers. Batch adsorption results showed that the
      millimeter-scale CA beads decorated by PANI nanofibers had high affinity to
      Cu(2+) and Pb(2+) in aqueous solutions. The removal percentages of Cu(2+) and
      Pb(2+) in aqueous solutions by this PANI/CA composite with milli/nano
      hierarchical structure surpassed 90% in a wide pH range from 3 to 7. Sorption of
      the two kinds of ions to PANI/CA composite sorbent agreed well with the
      Freundlich adsorption model. The adsorption kinetic results of Cu(2+) and Pb(2+)
      showed that the adsorption reached equilibrium within 120min and 40min,
      respectively. And their adsorption rates could be described by pseudo-second
      order kinetics. The desorption percentages of Pb(2+) and Cu(2+) from this PANI/CA
      composite are 62% and 75%, respectively. The Pb(2+) and Cu(2+) removal capacity
      of the sorbent could be further reinforced when the diameter of CA beads turned
      from millimeter to micrometer.

PMID- 22410719
TI  - Effect of second coagulant addition on coagulation efficiency, floc properties
      and residual Al for humic acid treatment by Al13 polymer and polyaluminum
      chloride (PACl).
AB  - Influence of second dose on coagulation efficiency, floc re-growth, fractal
      structure and residual Al of the effluent in humic acid (HA) coagulation with
      Al(13) polymer ([Al(13)O(4)(OH)(24)(H(2)O)(12)](7+)) and PACl were comparatively
      investigated in this study. Effects of breakage shear on the floc properties
      generated in the coagulation with and without additional dose were also
      investigated. The results indicated that additional dose during breakage could
      essentially improve the HA removal efficiency and floc re-growth in both Al(13)
      and PACl coagulations. Second doses of Al(13) at 0.5 and 1.0mg/L resulted in
      better turbidity and UV(254) removal as well as floc re-growth rather than higher
      additional dose of 1.5 and 2.0mg/L; while in PACl coagulation, more efficient HA
      removal and better floc re-growth were obtained at higher additional doses (1.0,
      1.5 and 2.0mg/L). Small additional Al(13) could apparently increase the D(f) of
      re-formed flocs while the additional PACl displayed inconspicuous effect on floc
      D(f). The additional coagulant dose could alleviate the further decrease of re
      grown floc size with increased breakage shear for both coagulants. The residual
      Al analysis implied that two-stage addition contributed to lower residual Al in
      effluent than one-time addition mode with the same total coagulant concentration.

PMID- 22410720
TI  - Removing organic contaminants with bifunctional iron modified rectorite as
      efficient adsorbent and visible light photo-Fenton catalyst.
AB  - Iron-modified rectorite (FeR) was prepared as both adsorbent and catalyst. The
      iron modification increased layer-to-layer spacing and surface area of rectorite,
      leading to much increased adsorption of Rhodamine B (RhB) on rectorite. The
      maximum adsorption capacity of RhB on FeR reached 101mgg(-1) at pH 4.5, being 11
      folds of that on the unmodified one. The iron modification also enabled rectorite
      to have efficient visible light photocatalytic ability. The apparent rate
      constant for the degradation of RhB (80MUM) at 298K and pH 4.5 in the presence of
      H(2)O(2) (6.0mM) and FeR (0.4gL(-1)) was evaluated to be 0.0413min(-1) under
      visible light and 0.122min(-1) under sunlight, respectively. The analysis with
      electron spin resonance spin-trapping technique supported that the iron modified
      rectorite effectively catalyzed the decomposition of H(2)O(2) into hydroxyl
      radicals. On the basis of the characterization and analysis, the new bifunctional
      material was well clarified as both adsorbent and photocatalyst in the removing
      of organic pollutants.

PMID- 22410721
TI  - Kinetic and mechanistic study of microcystin-LR degradation by nitrous acid under
      ultraviolet irradiation.
AB  - Degradation of microcystin-LR (MC-LR) in the presence of nitrous acid (HNO(2))
      under irradiation of 365nm ultraviolet (UV) was studied for the first time. The
      influence of initial conditions including pH value, NaNO(2) concentration, MC-LR
      concentration and UV intensity were studied. MC-LR was degraded in the presence
      of HNO(2); enhanced degradation of MC-LR was observed with 365nm UV irradiation,
      caused by the generation of hydroxyl radicals through the photolysis of HNO(2).
      The degradation processes of MC-LR could well fit the pseudo-first-order
      kinetics. Mass spectrometry was applied for identification of the byproducts and
      the analysis of degradation mechanisms. Major degradation pathways were proposed
      according to the results of LC-MS analysis. The degradation of MC-LR was
      initiated via three major pathways: attack of hydroxyl radicals on the conjugated
      carbon double bonds of Adda, attack of hydroxyl radicals on the benzene ring of
      Adda, and attack of nitrosonium ion on the benzene ring of Adda.

PMID- 22410722
TI  - Preparation of lead oxide nanoparticles from cathode-ray tube funnel glass by
      self-propagating method.
AB  - This paper presents a novel process of extracting lead oxide nanoparticles from
      cathode-ray tube (CRT) funnel glass using self-propagating high-temperature
      synthesis (SHS) method. The impacts of added amount of funnel glass on the
      extraction ratio of lead, the lead extraction velocity and the micromorphology,
      as well as particle size of extracted nanoparticles were investigated. We found
      that self-propagating reaction in the presence of Mg and Fe(2)O(3) could separate
      lead preferentially and superfine lead oxide nanoparticles were obtained from a
      collecting chamber. The separation ratio was related closely to the amount of
      funnel glass added in the original mixture. At funnel glass addition of no more
      than 40wt.%, over 90wt.% of lead was recovered from funnel glass. High extraction
      yield reveals that the network structure of funnel glass was fractured due to the
      dramatic energy generated during the SHS melting process. The PbO nanoparticles
      collected show good dispersion and morphology with a mean grain size of 40-50nm.

PMID- 22410723
TI  - Pilot-scale washing of metal contaminated garden soil using EDTA.
AB  - Ten batches (75kg each) of garden soil with >50% of silt and clay and average
      1935mgkg(-1) Pb, 800mgkg(-1) Zn, 10mgkg(-1) Cd and 120mgkg(-1) As were remediated
      in a pilot-scale chemical extraction plant. Washing with 60mmol
      ethylenediaminetetraacetic acid (EDTA) per kg of soil on average removed 79, 38,
      70, and 80% of Pb, Zn, Cd and As, respectively, and significantly reduced the
      leachability, phyto-accessibility and oral-availability of residual toxic metals,
      as assessed using deionised water, toxicity characteristic leaching procedure
      (TCLP), diethylenetriamine pentaacetic acid extraction (DTPA) and physiologically
      based extraction test (PBET) tests. The used soil washing solution was treated
      before discharge using an electrochemical advanced oxidation process with
      graphite anode: EDTA was removed by degradation and toxic metals were electro
      precipitated onto a stainless steel cathode. The novelty of the remediation
      technique is separation of the soil from the washing solution and soil rinsing
      (removal of mobilized contaminants) carried out in the same process step. Another
      novelty is the reuse of the soil rinsing solution from the previous batch for
      cleansing the soil sand, soil rinsing and for preparation of the washing solution
      in subsequent batches. The cost of energy and material expenses and disposal of
      waste products amounted to approximately 75?ton(-1) of soil.

PMID- 22410724
TI  - Enhancing the adsorption of vapor-phase mercury chloride with an innovative
      composite sulfur-impregnated activated carbon.
AB  - Mercury chloride (HgCl(2)) is the major mercury derivate emitted from municipal
      solid waste incinerators, which has high risk to the environment and human
      health. This study investigated the adsorption of vapor-phase HgCl(2) with an
      innovative composite sulfurized activated carbon (AC), which was derived from the
      pyrolysis, activation, and sulfurization of waste tires. The composite sulfur
      impregnation process impregnated activated carbon with aqueous-phase sodium
      sulfide (Na(2)S) and followed with vapor-phase elemental sulfur (S(0)).
      Thermogravimetric analysis (TGA) was applied to investigate the adsorptive
      capacity of vapor-phase HgCl(2) using the composite sulfurized AC. The operating
      parameters included the types of composite sulfurized AC, the adsorption
      temperature, and the influent HgCl(2) concentration. Experimental results
      indicated that the sulfur-impregnation process could increase the sulfur content
      of the sulfurized AC, but decreased its specific surface area. This study further
      revealed that the composite sulfurized AC impregnated with aqueous-phase Na(2)S
      and followed with vapor-phase S(0) (Na(2)S+S(0) AC) had much higher saturated
      adsorptive capacity of HgCl(2) than AC impregnated in the reverse sequence
      (S(0)+Na(2)S AC). A maximum saturated adsorptive capacity of HgCl(2) up to 5236
      MUg-HgCl(2)/g-C was observed for the composite Na(2)S+S(0) AC, which was
      approximately 2.00 and 3.17 times higher than those for the single Na(2)S and
      S(0) ACs, respectively.

PMID- 22410725
TI  - Achieving very low mercury levels in refinery wastewater by membrane filtration.
AB  - Microfiltration (MF), ultrafiltration (UF), nanofiltration (NF) and reverse
      osmosis (RO) membranes were evaluated for their ability to achieve the world's
      most stringent Hg discharge criterion (<1.3ng/L) in an oil refinery's wastewater.
      The membrane processes were operated at three different pressures to demonstrate
      the potential for each membrane technology to achieve the targeted effluent
      mercury concentrations. The presence of mercury in the particulate form in the
      refinery wastewater makes the use of MF and UF membrane technologies more
      attractive in achieving very low mercury levels in the treated wastewater. Both
      NF and RO were also able to meet the target mercury concentration at lower
      operating pressures (20.7bar). However, higher operating pressures (>=34.5bar)
      had a significant effect on NF and RO flux and fouling rates, as well as on
      permeate quality. SEM images of the membranes showed that pore blockage and
      narrowing were the dominant fouling mechanisms for the MF membrane while surface
      coverage was the dominant fouling mechanism for the other membranes. The
      correlation between mercury concentration and particle size distribution was also
      investigated to understand mercury removal mechanisms by membrane filtration. The
      mean particle diameter decreased with filtration from 1.1+/-0.0MUm to 0.74+/
      0.2MUm after UF.

PMID- 22410726
TI  - Effect of fly ash on biochemical responses and DNA damage in earthworm,
      Dichogaster curgensis.
AB  - Fly ash is receiving alarming attention due to its hazardous nature, widespread
      usage, and the manner of disposal; leading to environmental deterioration. We
      carried out bio-monitoring and risk assessment of fly ash in earthworms as a
      model system. Dichogaster curgensis were allowed to grow in presence or absence
      of fly ash (0-40%, w/w) for 1, 7, and 14 d. The biochemical markers viz. catalase
      (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione
      peroxidase (GPx), glutathione S-transferase (GST), and malondialdehyde (MDA)
      level were measured. The comet and neutral red retention assays were performed on
      earthworm coelomocytes to assess genetic damages and lysosomal membrane
      stability. The results revealed increased activities of SOD, GPx, GST, and MDA
      level in a dose-response manner while GR activity was decreased with increasing
      concentrations of fly ash. No obvious trend was observed in the CAT activity and
      fly ash concentration. Lysosomal membrane destabilization was noted in the
      earthworms exposed to 5% and more fly ash concentration in a dose and time
      dependent manner. The comet assay demonstrated that the fly ash induced DNA
      damage and DNA-protein crosslinks in earthworm coelomocytes.

PMID- 22410727
TI  - Large-scale spatial and interspecies differences in trace elements and stable
      isotopes in marine wild fish from Chinese waters.
AB  - We conducted a large scale investigation of twelve trace element levels and
      stable isotopes (delta(13)C and delta(15)N) in twenty-nine marine wild fish
      species collected from Chinese coastal waters. Trace element levels varied
      significantly with species. Clear spatial variations were found for Al, As, Cd,
      Cr, Fe, Ni, and Pb, whereas Ag, Cu, Mo, Se and Zn did not show much spatial
      variation. The Pearl River Estuary contained the highest concentrations of Al,
      Cr, Ni, and Pb, whereas the most southern waters (Haikou) contained the lowest
      concentrations of Al, Fe, and Pb. There was no correlation between log
      transformed trace elements concentrations and delta(15)N values or delta(13)C
      values, indicating no biomagnification among these trace elements. The calculated
      hazard quotients (HQ) of 10 elements were less than 1, thus there was no obvious
      health risk from the intake of trace elements through marine wild fish
      consumption.

PMID- 22410728
TI  - A regenerative method of tympanic membrane repair could be the greatest advance
      in otology since the cochlear implant.

PMID- 22410729
TI  - Recovery from forward masking in elderly cochlear implant users.
AB  - OBJECTIVE: To compare temporal aspects of peripheral neural responses and central
      auditory perception between groups of younger adult and elderly cochlear implant
      users. STUDY DESIGN: Cohort study. SETTING: Academic hospital and cochlear
      implant center. PATIENTS: Adult cochlear implant users aged 28 to 57 years in the
      younger group (n = 5) and 61 to 89 years (n = 9) in the elderly group. All
      subjects used Advanced Bionics devices. INTERVENTION: Diagnostic. MAIN OUTCOME
      MEASURES: Time constants of neural (i.e., electrically evoked compound action
      potentials [ECAPs]) and perceptual recovery from forward masking. Interstimulus
      intervals (ISIs) were varied in both experiments. RESULTS: ECAP recovery rates
      were equivalent between groups, and no correlation was found between ECAP
      recovery and age. No correlations were found between ECAP recovery and speech
      perception. Psychophysical recovery was significantly slower in the elderly
      compared with the younger subjects (p < 0.0005), with a significant effect of age
      (R2 = 0.70, p < 0.0005). At the longest ISI (240 ms), elderly subjects
      experienced a mean maximum threshold shift of 35.2% (relative to 1 ms ISI) versus
      14.8% for younger subjects. There was a significant positive relationship between
      psychophysical recovery and consonant-nucleus-consonant word scores (R2 = 0.62, p
      < 0.001), although no relationship was found with Hearing in Noise Test
      sentences. CONCLUSION: These findings suggest that difficulties observed in
      speech perception by elderly CI users may be due to age-related changes in the
      central rather than peripheral auditory system. With further study, these results
      may provide information to allow clinicians to assess patients' temporal
      processing abilities and facilitate setting program parameters that will maximize
      their auditory perceptual experience with a cochlear implant.

PMID- 22410730
TI  - The relationship between individual ossicular status and conductive hearing loss
      in cholesteatoma.
AB  - OBJECTIVE: To investigate and analyze the relationship between individual
      ossicular erosion and air-bone gap (ABG) among patients with cholesteatoma. STUDY
      DESIGN: Retrospective case review. SETTING: Tertiary referral center. SUBJECTS
      AND METHODS: Data from all patients undergoing an initial surgery for
      cholesteatoma were retrospectively reviewed to evaluate the relationships between
      preoperative pure tone audiometry data, intraoperative assessment of individual
      ossicular destruction, and clinical characterization of cholesteatoma. For each
      patient, the cholesteatoma was categorized as primary acquired, secondary
      acquired, congenital, or unable to discern. Ossicular destruction was graded, and
      ABG was calculated. For each ossicle, the relationship between degree of
      cholesteatoma involvement and ossicular erosion and the ABG was analyzed using
      univariate and multivariate linear regression. RESULTS: A total of 158 primary
      cholesteatoma surgeries were performed by the senior author between 1992 and 2009
      that met our inclusion criteria. The status of each ossicle was significantly
      associated with the ABG in a graded and independent manner; this association was
      most significant for the incus. Cholesteatoma abutting an intact ossicle did not
      significantly affect the ABG. Clinical categorization of cholesteatoma was not
      significantly associated with the ABG. CONCLUSION: Previous assessments of
      ossicular destruction have provided limited information about the relationship
      between ossicular destruction and ABG in cholesteatoma patients. Through the use
      of a new and detailed grading scale, this study reveals that the erosion of each
      ossicle contributes in a graded and independent manner to the increase in ABG,
      with the status of the incus having the most statistically significant
      association with ABG.

PMID- 22410731
TI  - Feedback analysis in percutaneous bone-conduction device and bone-conduction
      implant on a dry cranium.
AB  - HYPOTHESIS: The bone-conduction implant (BCI) can use a higher gain setting
      without having feedback problems compared with a percutaneous bone-conduction
      device (PBCD). BACKGROUND: The conventional PBCD, today, is a common treatment
      for patients with conductive hearing loss and single-sided deafness. However,
      there are minor drawbacks reported related to the percutaneous implant and
      specifically poor high-frequency gain. The BCI system is designed as an
      alternative to the percutaneous system because it leaves the skin intact and is
      less prone to fall into feedback oscillations, thus allowing more high-frequency
      gain. METHODS: Loop gains of the Baha Classic 300 and the BCI were measured in
      the frequency range of 100 to 10,000 Hz attached to a Skull simulator and a dry
      cranium. The Baha and the BCI positions were investigated. The devices were
      adjusted to full-on gain. RESULTS: It was found that the gain headroom using the
      BCI was generally 0 to 10 dB better at higher frequencies than using the Baha for
      a given mechanical output. More specifically, if the mechanical output of the
      devices were normalized at the cochlear level the improvement in gain headroom
      with the BCI versus the Baha were in the range of 10 to 30 dB. CONCLUSION: Using
      a BCI, significantly higher gain setting can be used without feedback problems as
      compared with using a PBCD.

PMID- 22410732
TI  - Sheep as a large animal model for middle and inner ear implantable hearing
      devices:  a feasibility study in cadavers.
AB  - OBJECTIVE: Currently, no large animal model exists for surgical-experimental
      exploratory analysis of implantable hearing devices. In a histomorphometric
      study, we sought to investigate whether sheep or pig cochleae are suitable for
      this purpose and whether device implantation is feasible. METHODS: Skulls of pig
      and sheep cadavers were examined using high-resolution 128-slice computed
      tomography (CT) to study anatomic relationships. A cochlear implant and an active
      middle ear implant could be successfully implanted into the sheep's inner and
      middle ear, respectively. Correct device placement was verified by CT and
      histology. The cochlear anatomy of the sheep was further studied by micro-CT and
      histology. RESULTS: Our investigations indicate that the sheep is a suitable
      animal model for implantation of implantable hearing devices. The implantation of
      the devices was successfully performed by access through a mastoidectomy. The
      histologic, morphologic, and micro-CT study of the sheep cochlea showed that it
      is highly similar to the human cochlea. The temporal bone of the pig was not
      suitable for these microsurgical procedures because the middle and inner ear were
      not accessible owing to distinct soft and fatty tissue coverage of the mastoid.
      CONCLUSION: The sheep is an appropriate large animal model for experimental
      studies with implantable hearing devices, whereas the pig is not.

PMID- 22410734
TI  - Diffuse reflectance spectroscopy as a tool to measure the absorption coefficient
      in skin: system calibration.
AB  - An individualised laser skin treatment may enhance the treatment and reduces
      risks and side-effects. The optical properties (absorption and scattering
      coefficients) are important parameters in the propagation of laser light in skin
      tissue. The differences in the melanin content of different skin phototypes
      influence the absorption of the light. The absorption coefficient at the
      treatment wavelength for an individual can be determined by diffuse reflectance
      spectroscopy, using a probe containing seven fibres. Six of the fibres deliver
      the light to the measurement site and the central fibre collects the diffused
      reflected light. This is an in vivo technique, offering benefits for near-real
      time results. Such a probe, with an effective wavelength band from 450 to 800 nm,
      was used to calibrate skin-simulating phantoms consisting of intralipid and ink.
      The calibration constants were used to calculate the absorption coefficients from
      the diffuse reflectance measurements of three volunteers (skin phototypes, II, IV
      and V) for sun-exposed and non-exposed areas on the arm.

PMID- 22410735
TI  - Functional roles of gangliosides in neurodevelopment: an overview of recent
      advances.
AB  - Gangliosides are sialic acid-containing glycosphingolipids that are most abundant
      in the nervous system. They are localized primarily in the outer leaflets of
      plasma membranes and participated in cell-cell recognition, adhesion, and signal
      transduction and are integral components of cell surface microdomains or lipid
      rafts along with proteins, sphingomyelin and cholesterol. Ganglioside-rich lipid
      rafts play an important role in signaling events affecting neural development and
      the pathogenesis of certain diseases. Disruption of gangloside synthase genes in
      mice induces developmental defects and neural degeneration. Targeting ganglioside
      metabolism may represent a novel therapeutic strategy for intervention in certain
      diseases. In this review, we focus on recent advances on metabolic and functional
      studies of gangliosides in normal brain development and in certain neurological
      disorders.

PMID- 22410736
TI  - Expression levels of the BDNF gene and histone modifications around its promoters
      in the ventral tegmental area and locus ceruleus of rats during forced abstinence
      from morphine.
AB  - Brain-derived neurotrophic factor (BDNF) plays a role in mediating molecular,
      cellular, and behavioral adaptations underlying drug addiction. Here, we examined
      the influence of withdrawal from repeated morphine treatment on the expression of
      BDNF mRNA in the ventral tegmental area (VTA) and locus coeruleus (LC) of the rat
      brain. We also studied whether alternations in mRNA levels of BDNF in these
      tissues are associated with histone modifications around promoters II and III of
      the BDNF gene. Thus, chromatin immunoprecipitation (CHIP) and quantitative (q)
      PCR were employed to assess acetylation of histone H3 at K9/K14 and
      trimethylation of histone H3 at K9. Results of qRT-PCR showed that levels of BDNF
      mRNA in both VTA and LC were significantly increased 7 days rather than 2 h or 24
      h following the last injection of morphine. Consistently, CHIP and qPCR analysis
      revealed that on day 7 of morphine abstinence, both VTA and LC levels of histone
      methylation at BDNF promoters II and III of morphine treated rats were
      significantly lower than control animals. Morphine withdrawal caused only a
      significant increase in H3 acetylation at the promoter II in the LC. These data
      demonstrate the involvement of histone H3 methylation in the regulation of gene
      expression in the VTA and LC of rats during forced abstinence of morphine.

PMID- 22410737
TI  - Pigment epithelium-derived factor released by Muller glial cells exerts
      neuroprotective effects on retinal ganglion cells.
AB  - Survival of retinal ganglion cells (RGC) is compromised in several vision
      threatening disorders such as ischemic and hypertensive retinopathies and
      glaucoma. Pigment epithelium-derived factor (PEDF) is a naturally occurring
      pleiotropic secreted factor in the retina. PEDF produced by retinal glial
      (Muller) cells is suspected to be an essential component of neuron-glial
      interactions especially for RGC, as it can protect this neuronal type from
      ischemia-induced cell death. Here we show that PEDF treatment can directly affect
      RGC survival in vitro. Using Muller cell-RGC-co-cultures we observed that
      activity of Muller-cell derived soluble mediators can attenuate hypoxia-induced
      damage and RGC loss. Finally, neutralizing the activity of PEDF in glia
      conditioned media partially abolished the neuroprotective effect of glia, leading
      to an increased neuronal death in hypoxic condition. Altogether our results
      suggest that PEDF is crucially involved in the neuroprotective process of
      reactive Muller cells towards RGC.

PMID- 22410738
TI  - Home sweet home: skin stem cell niches.
AB  - The epidermis and its appendages, such as the hair follicle (HF), continually
      regenerate throughout postnatal mammalian life due to the activity of resident
      epithelial stem cells (SCs). The follicular SC niche, or the bulge, is composed
      of a heterogeneous population of self-renewing multipotent cells. Multiple
      intrinsic molecular mechanisms promote the transition of follicular SCs from
      quiescence to activation. In addition, numerous extrinsic cell types influence
      the activity and characteristics of bulge cells. Ultimately, the balance between
      these intrinsic and extrinsic mechanisms influences the function of bulge cells
      during homeostasis and tissue regeneration and likely contributes to skin
      tumorigenesis. Here, we review both the intrinsic and extrinsic factors that
      contribute to the skin SC niche.

PMID- 22410739
TI  - E-cadherin plays an essential role in collective directional migration of large
      epithelial sheets.
AB  - In wound healing and development, large epithelial sheets migrate collectively,
      in defined directions, and maintain tight cell-cell adhesion. This type of
      movement ensures an essential function of epithelia, a barrier, which is lost
      when cells lose connection and move in isolation. Unless wounded, epithelial
      sheets in cultures normally do not have overall directional migration. Cell
      migration is mostly studied when cells are in isolation and in the absence of
      mature cell-cell adhesion; the mechanisms of the migration of epithelial sheets
      are less well understood. We used small electric fields (EFs) as a directional
      cue to instigate and guide migration of epithelial sheets. Significantly, cells
      in monolayer migrated far more efficiently and directionally than cells in
      isolation or smaller cell clusters. We demonstrated for the first time the group
      size-dependent directional migratory response in several types of epithelial
      cells. Gap junctions made a minimal contribution to the directional collective
      migration. Breaking down calcium-dependent cell-cell adhesion significantly
      reduced directional sheet migration. Furthermore, E-cadherin blocking antibodies
      abolished migration of cell sheets. Traction force analysis revealed an important
      role of forces that cells in the leading rows exert on the substratum. With EF,
      the traction forces of the leading edge cells coordinated in directional re
      orientation. Our study thus identifies a novel mechanism--E-cadherin dependence
      and coordinated traction forces of leading cells in collective directional
      migration of large epithelial sheets.

PMID- 22410740
TI  - Safeguarding bacterial resources promotes biotechnological innovation.
AB  - Environmental research delivers valuable bacterial resources for biotechnology.
      We believe that systematic long-term preservation of bacteria will promote future
      biotechnological innovations, by safeguarding the accessibility of bacteria
      already recognized to have interesting features and providing a "pool" of
      bacterial resources for novel applied research. To this end, we want to advocate
      the incorporation of preservation tests in environmental or applied
      microbiological research. This paper introduces non-specialists to different
      preservation methods for bacteria. Several parameters that influence long-term
      storage of bacterial resources are explained and practical tips and guidelines
      are formulated. Also, the vital role of public culture collections is highlighted
      and the state-of-the-art of preservation of non-pure cultures is described.

PMID- 22410741
TI  - Attachment of Acidithiobacillus ferrooxidans and Leptospirillum ferriphilum
      cultured under varying conditions to pyrite, chalcopyrite, low-grade ore and
      quartz in a packed column reactor.
AB  - The attachment of Acidithiobacillus ferrooxidans and Leptospirillum ferriphilum
      spp. grown on ferrous medium or adapted to a pyrite mineral concentrate to four
      mineral substrata, namely, chalcopyrite and pyrite concentrates, a low-grade
      chalcopyrite ore (0.5 wt%) and quartzite, was investigated. The quartzite
      represented a typical gangue mineral and served as a control. The attachment
      studies were carried out in a novel particle-coated column reactor. The saturated
      reactor containing glass beads, which were coated with fine mineral concentrates,
      provided a quantifiable surface area of mineral concentrate and maintained good
      fluid flow. A. ferrooxidans and Leptospirillum spp. had similar attachment
      characteristics. Enhanced attachment efficiency occurred with bacteria grown on
      sulphide minerals relative to those grown on ferrous sulphate in an ore-free
      environment. Selective attachment to sulphide minerals relative to gangue
      materials occurred, with mineral adapted cultures attaching to the minerals more
      efficiently than ferrous grown cultures. Mineral-adapted cultures showed highest
      levels of attachment to pyrite (74% and 79% attachment for A. ferrooxidans and L.
      ferriphilum, respectively). This was followed by attachment of mineral-adapted
      cultures to chalcopyrite (63% and 58% for A. ferrooxidans and L. ferriphilum,
      respectively). A. ferrooxidans and L. ferriphilum exhibited lower levels of
      attachment to low-grade ore and quartz relative to the sulphide minerals.

PMID- 22410742
TI  - Substrate range and enantioselectivity of epoxidation reactions mediated by the
      ethene-oxidising Mycobacterium strain NBB4.
AB  - Mycobacterium strain NBB4 is an ethene-oxidising micro-organism isolated from
      estuarine sediments. In pursuit of new systems for biocatalytic epoxidation, we
      report the capacity of strain NBB4 to convert a diverse range of alkene
      substrates to epoxides. A colorimetric assay based on 4-(4-nitrobenzyl)pyridine)
      has been developed to allow the rapid characterisation and quantification of
      biocatalytic epoxide synthesis. Using this assay, we have demonstrated that
      ethene-grown NBB4 cells epoxidise a wide range of alkenes, including terminal
      (propene, 1-butene, 1-hexene, 1-octene and 1-decene), cyclic (cyclopentene,
      cyclohexene), aromatic (styrene, indene) and functionalised substrates (allyl
      alcohol, dihydropyran and isoprene). Apparent specific activities have been
      determined and range from 2.5 to 12.0 nmol min(-1) per milligram of cell protein.
      The enantioselectivity of epoxidation by Mycobacterium strain NBB4 has been
      established using styrene as a test substrate; (R)-styrene oxide is produced in
      enantiomeric excesses greater than 95%. Thus, the ethene monooxygenase of
      Mycobacterium NBB4 has a broad substrate range and promising enantioselectivity,
      confirming its potential as a biocatalyst for alkene epoxidation.

PMID- 22410743
TI  - Isolation and characterization of Staphylococcus sp. strain NBRIEAG-8 from
      arsenic contaminated site of West Bengal.
AB  - Arsenic contaminated rhizospheric soils of West Bengal, India were sampled for
      arsenic resistant bacteria that could transform different arsenic forms.
      Staphylococcus sp. NBRIEAG-8 was identified by16S rDNA ribotyping, which was
      capable of growing at 30,000 mg l(-1) arsenate [As(V)] and 1,500 mg l(-1)
      arsenite [As(III)]. This bacterial strain was also characterized for arsenical
      resistance (ars) genes which may be associated with the high-level resistance in
      the ecosystems of As-contaminated areas. A comparative proteome analysis was
      conducted with this strain treated with 1,000 mg l(-1) As(V) to identify changes
      in their protein expression profiles. A 2D gel analysis showed a significant
      difference in the proteome of arsenic treated and untreated bacterial culture.
      The change in pH of cultivating growth medium, bacterial growth pattern
      (kinetics), and uptake of arsenic were also evaluated. After 72 h of incubation,
      the strain was capable of removing arsenic from the culture medium amended with
      arsenate and arsenite [12% from As(V) and 9% from As(III)]. The rate of
      biovolatilization of As(V) was 23% while As(III) was 26%, which was determined
      indirectly by estimating the sum of arsenic content in bacterial biomass and
      medium. This study demonstrates that the isolated strain, Staphylococcus sp., is
      capable for uptake and volatilization of arsenic by expressing ars genes and 8
      new upregulated proteins which may have played an important role in reducing
      arsenic toxicity in bacterial cells and can be used in arsenic bioremediation.

PMID- 22410744
TI  - Substrate specificity and gene expression of two Penicillium chrysogenum alpha-L
      arabinofuranosidases (AFQ1 and AFS1) belonging to glycoside hydrolase families 51
      and 54.
AB  - We previously isolated two alpha-L-arabinofuranosidases (ABFs), termed AFQ1 and
      AFS1, from the culture filtrate of Penicillium chrysogenum 31B. afq1 and afs1
      complementary DNAs encoding AFQ1 and AFS1 were isolated by in vitro cloning. The
      deduced amino acid sequences of AFQ1 and AFS1 are highly similar to those of
      Penicillium purpurogenum ABF 2 and ABF 1, respectively, which belong to glycoside
      hydrolase (GH) families 51 and 54, respectively. Pfam analysis revealed an "Alpha
      L-AF_C" domain in AFQ1 and "ArabFuran-catal" and "AbfB" domains in AFS1. Semi
      quantitative RT-PCR analysis indicated that the afq1 gene was constitutively
      expressed in P. chrysogenum 31B at a low level, although the expression was
      slightly induced with arabinose, arabinitol, arabinan, and arabinoxylan. In
      contrast, expression of the afs1 gene was strongly expressed by the above four
      carbohydrates and less strongly induced by galactan. Recombinant enzymes (rAFQ1
      and rAFS1) expressed in Escherichia coli were active against both p-nitrophenyl
      alpha-L-arabinofuranoside and polysaccharides with different specificities. (1)H
      NMR analysis revealed that rAFS1 degraded arabinofuranosyl side chains that were
      both singly and doubly linked to the backbones of arabinoxylan and L-arabinan. On
      the other hand, rAFQ1 preferentially released arabinose linked to C-3 of single
      substituted xylose or arabinose residues in the two polysaccharides.

PMID- 22410745
TI  - Whole-cell hydroxylation of n-octane by Escherichia coli strains expressing the
      CYP153A6 operon.
AB  - CYP153A6 is a well-studied terminal alkane hydroxylase which has previously been
      expressed in Pseudomonas putida and Escherichia coli by using the pCom8 plasmid.
      In this study, CYP153A6 was successfully expressed in E. coli BL21(DE3) by
      cloning the complete operon from Mycobacterium sp. HXN-1500, also encoding the
      ferredoxin reductase and ferredoxin, into pET28b(+). LB medium with IPTG as well
      as auto-induction medium was used to express the proteins under the T7 promoter.
      A maximum concentration of 1.85 MUM of active CYP153A6 was obtained when using
      auto-induction medium, while with IPTG induction of LB cultures, the P450
      concentration peaked at 0.6-0.8 MUM. Since more biomass was produced in auto
      induction medium, the specific P450 content was often almost the same, 0.5-1.0
      MUmol P450 g (DCW)-1, for both methods. Analytical scale whole-cell
      biotransformations of n-octane were conducted with resting cells, and it was
      found that high P450 content in biomass did not necessarily result in high
      octanol production. Whole cells from LB cultures induced with IPTG gave higher
      specific and volumetric octanol formation rates than biomass from auto-induction
      medium. A maximum of 8.7 g octanol L (BRM)-1 was obtained within 24 h (0.34 g L
      (BRM)-1  h-1) with IPTG-induced cells containing only 0.20 MUmol P450 g (DCW)-1,
      when glucose (22 g L (BRM)-1) was added for cofactor regeneration.

PMID- 22410746
TI  - Aoyap1 regulates OTA synthesis by controlling cell redox balance in Aspergillus
      ochraceus.
AB  - Among the various factors correlated with toxin production in fungi, oxidative
      stress is a crucial one. In relation to this, an important role is played by
      oxidative stress-related receptors. These receptors can transduce the "oxidative
      message" to the nucleus and promote a transcriptional change targeted at
      restoring the correct redox balance in the cell. In Aspergillus parasiticus, the
      knockout of the ApyapA gene, a homologue of the yeast Yap-1, disables the
      fungus's capacity to restore the correct redox balance in the cell. As a
      consequence, the onset of secondary metabolism and aflatoxins synthesis is
      triggered. Some clues as to the involvement of oxidative stress in the regulation
      of ochratoxin A (OTA) synthesis in Aspergillus ochraceus have already been
      provided by the disruption of the oxylipin-producer AoloxA gene. In this paper,
      we add further evidence that oxidative stress is also involved in the regulation
      of OTA biosynthesis in A. ochraceus. In fact, the use of certain oxidants and,
      especially, the deletion of the yap1-homologue Aoyap1 further emphasize the role
      played by this stress in controlling metabolic and morphological changes in A.
      ochraceus.

PMID- 22410747
TI  - Microwave-mediated heat transport in a quantum dot attached to leads.
AB  - The thermoelectric effect in a quantum dot (QD) attached to two leads in the
      presence of microwave fields is studied by using the Keldysh nonequilibrium Green
      function technique. When the microwave is applied only on the QD and in the
      linear response regime, the main peaks in the thermoelectric figure of merit and
      the thermopower are found to decrease, with the emergence of a set of photon
      induced peaks. Under this condition the microwave field cannot generate heat
      current or electrical bias voltage. Surprisingly, when the microwave field is
      applied only to one (bright) lead and not to the other (dark) lead or the QD,
      heat flows mostly from the dark to the bright lead, almost irrespective of the
      direction of the thermal gradient. We attribute this effect to microwave-induced
      opening of additional transport channels below the Fermi energy. The microwave
      field can change both the magnitude and the sign of the electrical bias voltage
      induced by the temperature gradient.

PMID- 22410748
TI  - The mechanical memory of lung myofibroblasts.
AB  - Fibroblasts differentiate into the highly synthetic and contractile myofibroblast
      phenotype when exposed to substrates with an elastic modulus corresponding to
      pathologically stiff fibrotic tissue. Cellular responses to changes in substrate
      stiffness are typically analyzed after hours or days, which does not enable the
      monitoring of myofibroblast persistence, a hallmark of fibrosis. To determine
      long-lasting effects on the fibrotic behavior of lung fibroblasts, we followed a
      novel approach of explanting and repeatedly passaging fibroblasts on silicone
      substrates with stiffness representing various states of lung health. Fibrotic
      activity was determined by assaying for myofibroblast proliferation, cell
      contractility, expression of alpha-smooth muscle actin, extracellular matrix and
      active TGFbeta1. As predicted, myofibroblast activity was low on healthy soft
      substrates and increased with increasing substrate stiffness. However, explanting
      and mechanically priming lung fibroblasts for 3 weeks on pathologically stiff
      substrates resulted in sustained myofibroblast activity even after the cells were
      returned to healthy soft cultures for 2 weeks. Such primed cells retained higher
      fibrotic activity than cells that had been exclusively cultured on soft
      substrates, and were not statistically different from cells continuously passaged
      on stiff surfaces. Inversely, priming lung fibroblasts for 3 weeks on soft
      substrates partially protected from myofibroblast activation after the shift to
      stiff substrates. Hence, mechano-sensed information relating to physical
      conditions of the local cellular environment could permanently induce fibrotic
      behavior of lung fibroblasts. This priming effect has important implications for
      the progression and persistence of aggressive fibrotic diseases such as
      idiopathic pulmonary fibrosis.

PMID- 22410749
TI  - First autologous hematopoietic SCT for ankylosing spondylitis: a case report and
      clues to understanding the therapy.

PMID- 22410750
TI  - Prophylaxis and treatment of GVHD after allogeneic haematopoietic SCT: a survey
      of centre strategies by the European Group for Blood and Marrow Transplantation.
AB  - Recommendations on indications for allogeneic haematopoietic SCT have been
      presented, but transplantation techniques remain poorly standardized. Pre
      transplant risk factors are well defined, and reported outcomes vary markedly
      among patients with similar risk characteristics. It would be of importance to
      know the impact of differences in treatment procedures. To study properly the
      different components of allogeneic transplantation, standardization of at least
      some central procedures would be needed. As the first step, the European Group
      for Blood and Marrow Transplantation (EBMT) performed a survey among all its 372
      member centres performing allogeneic transplantations about their strategies in
      preventing and treating GVHD. Responses from 79 centres (21% return) from 25
      countries (60% return) were received. Although some trends toward more uniform
      policies compared with a survey carried out 15 years earlier were observed, the
      present survey still showed marked variability in the GVHD prophylaxis and
      treatment strategies. On the basis of these findings, EBMT is developing a
      consensus process aiming at a standardized strategy.

PMID- 22410751
TI  - Extramedullary disease in plasma cell myeloma: the iceberg phenomenon.
AB  - Extramedullary (EM) plasmacytomas (EMPs) that are not progression of
      intramedullary (IM) plasma cell myeloma (PCM) are usually indolent. In contrast,
      EM spread of IM PCM is associated with a poor prognosis. The recently introduced
      Durie-Salmon PLUS staging system includes EM disease in the poor prognosis
      category. One study noted an increase in EM disease both at diagnosis and during
      follow-up of PCM in 2000-2007 compared with previous years raising concerns that
      adoption of novel agents (thalidomide, lenalidomide and bortezomib) and greater
      use of hematopoietic cell transplantation (HCT) might be contributory to this. It
      is uncertain if this is a true increase or merely greater detection due to the
      increasing use of more sensitive imaging techniques (computerized tomography,
      magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission
      tomography) or a reflection of the evolving natural history of PCM in an era when
      patients are living longer (median overall survival before 1996 was 29.9 months
      vs 44.8 months after 1996). Recent studies suggest there are important biological
      differences between PCM with or without EM spread that are offering clues that
      might explain the propensity for dissemination and a more aggressive clinical
      course. For example, EM relapse in PCM with and without deletion 13 was 30.8 vs
      5.6%, suggesting the biology of a plasma cell subclone before HCT can affect the
      nature of the relapse after HCT. This article will explore the clinical,
      biological and treatment implications of EM spread of PCM. In addition, the
      impact of extramedullary disease on the outcomes of autologous and allogeneic HCT
      for PCM will be analyzed. Allogeneic HCT early in the course of high-risk PCM
      with EM disease is a consideration since graft vs myeloma effects may be
      essential to achieve maximal survival benefits.

PMID- 22410752
TI  - Early evaluation of immune reconstitution following allogeneic CD3/CD19-depleted
      grafts from alternative donors in childhood acute leukemia.
AB  - Graft engineering procedures for hematopoietic SCT (HSCT) may improve the chance
      of success in matched unrelated donor (MUD) and haploidentical donor
      transplantations. Successful donor immune reconstitution is important to mediate
      GVL effects in reduced-intensity conditioning (RIC) HSCT. We prospectively
      investigated early immune reconstitution and clinical outcome in 30 CD3/CD19
      depleted MUD (n=15) or HP (n=15) HSCTs for high-risk childhood leukemia using a
      fludarabine-based RIC without serotherapy. The graft consisted of a mean of 10.5
      * 10(6)/kg CD34+, 77 * 10(3)/kg CD3+ and 39 * 10(6)/kg CD56+ cells. After
      transplantation, 86% of the patients engrafted. In all, 13% of patients had
      >grade 3 acute GVHD. Natural killer (NK) cell, DC and T-cell recovery achieved
      normal values within the first 60 days after transplantation. DC recovery was
      dominated by the DC2(-) subset. NK-cell phenotype was altered and cytotoxicity
      was lower compared with their donors. EFS was 50+/-9% (73+/-11% for those in CR1
      and 26+/-11% for those with advanced disease). Faster DC2(-) recovery was
      associated with better outcome, especially in the MUD setting. In summary,
      CD3/CD19-depleted HSCT with fludarabine-based RIC without serotherapy resulted in
      favorable patient survival, and rapid NK, DC and T-cell recovery.

PMID- 22410754
TI  - Acetone-butanol-ethanol (ABE) fermentation using Clostridium acetobutylicum XY16
      and in situ recovery by PDMS/ceramic composite membrane.
AB  - PDMS/ceramic composite membrane was directly integrated with acetone-butanol
      ethanol (ABE) fermentation using Clostridium acetobutylicum XY16 at 37  degrees C
      and in situ removing ABE from fermentation broth. The membrane was integrated
      with batch fermentation, and approximately 46 % solvent was extracted. The
      solvent in permeates was 118 g/L, and solvent productivity was 0.303 g/(L/h),
      which was approximately 33 % higher compared with the batch fermentation without
      in situ recovery. The fed-batch fermentation with in situ recovery by
      pervaporation continued for more than 200 h, 61 % solvent was extracted, and the
      solvent in penetration was 96.2 g/L. The total flux ranged from 0.338 to 0.847
      kg/(m(2)/h) and the separation factor of butanol ranged from 5.1 to 27.1 in this
      process. The membrane was fouled by the active fermentation broth, nevertheless
      the separation performances were partially recovered by offline membrane
      cleaning, and the solvent productivity was increased to 0.252 g/(L/h), which was
      19 % higher compared with that in situ recovery process without membrane
      cleaning.

PMID- 22410753
TI  - Entorhinal cortex atrophy differentiates Parkinson's disease patients with and
      without dementia.
AB  - Volumetric measures of mesial temporal lobe structures on MRI scans recently have
      been explored as potential biomarkers of dementia in patients with PD, with
      investigations primarily focused on hippocampal volume. Both in vivo MRI and
      postmortem tissue studies in Alzheimer's disease, however, demonstrate that the
      entorhinal cortex (ERC) is involved earlier in disease-related pathology than the
      hippocampus. The ERC, a region integral in declarative memory function, projects
      multimodal sensory information to the hippocampus through the perforant path. In
      PD, ERC atrophy, as measured on MRI, however, has received less attention,
      compared to hippocampal atrophy. We compared ERC and hippocampal atrophy in 12
      subjects with PD dementia including memory impairment, 14 PD subjects with normal
      cognition, and 14 healthy controls with normal cognition using manual
      segmentation methods on MRI scans. Though hippocampal volumes were similar in the
      two PD cognitive groups, ERC volumes were substantially smaller in the demented
      PD subjects, compared to cognitively normal PD subjects (P < 0.05). In addition,
      normalized ERC and hippocampal volumes for right and left hemispheres were
      significantly lower in the demented PD group, compared to healthy controls. Our
      findings suggest that ERC atrophy differentiates demented and cognitively normal
      PD subjects, in contrast to hippocampal atrophy. Thus, ERC atrophy on MRI may be
      a potential biomarker for dementia in PD, particularly in the setting of memory
      impairment.

PMID- 22410755
TI  - Symptoms of anxiety and associated risk and protective factors in young Asian
      American children.
AB  - Anxiety is one of the most prevalent mental health problems in young children but
      there has been a dearth of studies focusing on Asian American children. This
      study examines the patterns and the predictors of childhood anxiety and related
      symptoms in young children in a diverse Asian American (ASA) sample (n = 101).
      Findings indicate that ASA children are at higher risk for anxiety, somatization,
      and depressive problems than their peers. Parents' level of acculturation (i.e.,
      American identity, English competence), parental negative emotion socialization,
      conflicted parent-child relationship, child emotional knowledge and adaptive
      skills, as well as teachers' ethnic background and school class types were all
      associated with ASA children's anxiety. A combination of cultural, family, and
      school factors explained from 17 to 39 % of the variance in anxiety symptoms.
      Findings inform prevention services for young ASA children.

PMID- 22410756
TI  - [Sleep-disordered breathing and cardiac resynchronization therapy].
AB  - Patients with progressive heart failure often suffer from sleep-disordered
      breathing (SDB). Upon receiving cardiac resynchronization therapy (CRT), there is
      an improvement of cardiac function and central sleep apnea syndrome (CSA) with
      Cheyne-Stokes respiration; however, effects of CRT on obstructive sleep apnea
      syndrome seemed to be without clinical relevance. Likewise, additional atrial
      overdrive pacing did not improve CRT effects relevantly in CSA patients. During
      CRT, there is an improvement in sleep parameters, sleep quality by reduction of
      depressive syndromes, and in long-term survival. Therefore, all patients with
      chronic heart failure and indication for CRT should be monitored regarding SDB
      before and after CRT device implantation.

PMID- 22410757
TI  - VT ablation in heart failure.
AB  - Ventricular tachycardias (VT), shocks, and clusters of shock are ominous signs in
      patients with implantable cardioverter-defibrillators and herald an increased
      risk of hospitalization and mortality. VT clusters have been associated with
      aggravation of heart failure (19%), acute coronary events (14%), and electrolyte
      imbalance (10%). Yet, any association of potential causative factors and
      aggravation of VT is vague. Maybe, in patients with any substrate for re-entry,
      progressive aggravation of ventricular dysrhythmias is to be expected. The high
      recurrence rate of electrical storm despite antiarrhythmic drug therapy supports
      this view. The optimal timing of VT ablation is unknown, but current convention
      is to perform VT ablation after shock clusters or incessant VT has occurred.
      Preemptive VT ablation before VT has occurred is rarely performed (only in 15% of
      active centers) and the majority of centers never perform VT ablation even after
      the first shock. Such practice is within guidelines that recommend VT ablation
      only in ICD patients with recurrent or incessant VT. However, there is strong
      data in support of preemptive VT ablation.

PMID- 22410758
TI  - An appeal to medical journal editors: the need for a full description of
      laboratory methods and specimen handling in clinical study reports.

PMID- 22410759
TI  - Systemic mastocytosis in adults: 2012 Update on diagnosis, risk stratification,
      and management.
AB  - DISEASE OVERVIEW: Systemic mastocytosis (SM) results from a clonal proliferation
      of abnormal mast cells (MC) in one or more extra-cutaneous organs. DIAGNOSIS: The
      major criterion is presence of multifocal clusters of morphologically abnormal MC
      in the bone marrow. Minor diagnostic criteria include elevated serum tryptase
      level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V. RISK
      STRATIFICATION: The prognostic relevance of the 2008 World Health Organization
      (WHO) classification of SM has recently been confirmed. Classification of SM
      patients into indolent (SM), aggressive SM (ASM), SM associated with a clonal non
      MC lineage disease (SM-AHNMD) and mast cell leukemia (MCL) subgroups is a useful
      first step in establishing prognosis. MANAGEMENT: SM treatment is generally
      palliative. ISM patients have a normal life expectancy and receive symptom
      directed therapy; infrequently, cytoreductive therapy may be indicated for
      refractory symptoms. ASM patients have disease-related organ dysfunction;
      interferon-alpha (+/-corticosteroids) can control dermatological, hematological,
      gastrointestinal, skeletal, and mediator-release symptoms, but is hampered by
      poor tolerability. Similarly, cladribine has broad therapeutic activity, with
      particular utility when rapid MC debulking is indicated; the main toxicity is
      myelosuppression. Imatinib has a therapeutic role in the presence of an imatinib
      sensitive KIT mutation or in KITD816-unmutated patients. Treatment of SM-AHNMD is
      governed primarily by the non-MC neoplasm; hydroxyurea has modest utility in this
      setting. INVESTIGATIONAL DRUGS: Dasatinib's in vitro anti-KITD816V activity has
      not translated into significant therapeutic activity in most SM patients. In
      contrast, preliminary data suggest that Midostaurin may produce significant
      decreases in MC burden in some patients.

PMID- 22410760
TI  - Forced degradation studies of corticosteroids with an alumina-steroid-ethanol
      model for predicting chemical stability and degradation products of pressurized
      metered-dose inhaler formulations.
AB  - An alumina (Al(2)O(3))-steroid-ethanol model is used for forced degradation
      testing of corticosteroids to predict chemical stability and degradation products
      in pressurized metered-dose inhaler (pMDI) solution formulations. The model
      involves an ethanolic solution of a test steroid with Al(2)O(3), stressed at
      elevated temperatures to mimic the chemical interaction of drug, excipient, and
      packaging (an aluminum aerosol canister). The reactivity order of eight synthetic
      corticosteroids toward Al(2)O(3)-induced reactions is ranked with the stress
      model. The corticosteroids containing a C21-OH group possess the highest
      reactivity, suggesting that aluminum canisters with an inert interior coating are
      needed to stabilize their solution pMDIs. The Al(2)O(3)-induced degradation
      products and degradation pathways of a steroid containing C21-OH and
      triamcinolone acetonide are presented, and the role of Al(2)O(3) in the
      degradation pathways is briefly discussed. A potential degradation profile of
      beclomethasone dipropionate (BDP) established with an Al(2)O(3)-BDP-ethanol
      stress model is the same as the actual degradation profile of the BDP pMDI
      product, indicating that the model indeed predicts the degradation products.

PMID- 22410761
TI  - Interleukin-10 and interferon-gamma patterns during tuberculosis treatment:
      possible association with recurrence.
AB  - Interleukin (IL) 10 and interferon-gamma (IFN-) levels in induced sputum
      supernatants of 21 tuberculosis (TB) patients at diagnosis and during
      chemotherapy were correlated to recurrence rates. IL-10 decreased until day 60 of
      treatment (T60), and between T60 and T180 it increased again  in 7 cases (Pattern
      1) and further decreased in 14 cases (Pattern 2). Follow-up of 69 months was
      performed in 20/21 cases; 6 had recurrence of TB, of which 5/7 (71%) had Pattern
      1 and 1/13 (7.7%) Pattern 2 (OR 30.0, 95%CI 2.19411.3, P 0.0072). This was not
      observed for IFN-. High IL-10  levels at the end of treatment may function as a
      risk factor for TB recurrence.

PMID- 22410762
TI  - Exploring chemistry with the fragment molecular orbital method.
AB  - The fragment molecular orbital (FMO) method makes possible nearly linear scaling
      calculations of large molecular systems, such as water clusters, proteins and
      DNA. In particular, FMO has been widely used in biochemical applications
      involving protein-ligand binding and drug design. The method has been efficiently
      parallelized suitable for petascale computing. Many commonly used wave functions
      and solvent models have been interfaced with FMO. We review the historical
      background of FMO, and summarize its method development and applications.

PMID- 22410763
TI  - The role of allogeneic hematopoietic stem cell transplantation in the therapy of
      patients with acute lymphoblastic leukemia.
AB  - Allogeneic hematopoietic stem cell transplantation (alloHSCT) is an effective
      post-remission therapy in patients with acute lymphoblastic leukemia (ALL), but
      is associated with significant toxicity, so the optimal timing and use of this
      modality remains an issue of debate. Increased advances in reduced-intensity
      transplant preparative regimens and alternative donors has increased the
      accessibility of allogeneic transplantation. A risk adapted paradigm, using
      minimal residual disease analysis, may help in the selection of patients at
      highest risk for relapse, who may benefit most from alloHSCT. In this review, we
      summarize the indications for allogeneic transplantation within the risk-oriented
      paradigm, and also explore the latest literature on reduced intensity transplant
      regimens, as well as alternative donor transplantation for patients with ALL.

PMID- 22410764
TI  - Curing chronic myeloid leukemia.
AB  - The use of tyrosine kinase inhibitors (TKIs) targeted against the BCR-ABL1
      oncoprotein has proven remarkably successful in chronic myeloid leukemia (CML)
      and long-term survival has become a reality. Despite this outstanding progress,
      detection of minimal residual disease precludes therapy termination in most TKI
      receiving patients. CML has thus turned into a chronic illness, raising concerns
      about long-term safety, medication adherence, and health care costs. Although
      treatment cessation may be feasible in few selected patients achieving deep
      molecular responses, a definitive cure remains elusive owing to the discovery
      that TKIs spare quiescent leukemic stem cells (LSC). Understanding mechanisms
      underlying LSC behavior in TKI-treated patients may provide important clues to
      develop an array of strategies that ensure the complete destruction of LSC
      reservoirs and thereby offer CML patients a definitive cure.

PMID- 22410765
TI  - Research ethics in victimization studies: widening the lens.
AB  - Research ethics, especially the protection of research study participants, has
      been an enduring concern of investigators and scholars of victims of violence.
      Previous work has analyzed the overt and hidden risks of harm to study
      participants through poorly designed and implemented protocols, cross-cultural
      insensitivity, unjust exclusion of certain victim types, and neglect to ensure
      safety of research staff. This article extends this work by calling for greater
      attention to exploiting participants and victims as a class of persons. The need
      for this wider view derives from concern about the academic research environment
      with its emphasis on research, publication, and extramural funding. The authors
      argue that compliance with federal regulations and IRB directives is necessary
      but insufficient to conduct truly ethical research. Recognition of the unique
      pressures that researchers face in the context of the economically competitive
      university is required to delineate and manage exploitation risks. Such pressures
      have sometimes led to the rush from print to practices and policies with
      unintended harmful results for victims of violence as a class of persons. The
      authors suggest a number of strategies for researchers to define and manage the
      dangers of engaging in this type of unethical conduct.

PMID- 22410766
TI  - Gendered violence and the ethics of social science research.

PMID- 22410767
TI  - Commentary.

PMID- 22410768
TI  - Research ethics in victimization studies: widening the lens: a response and
      alternative view.

PMID- 22410769
TI  - Research ethics in victimization studies: widening the lens.

PMID- 22410771
TI  - Victim advocates' perceptions of legal work.
AB  - Past scholarship has weighed the risks and rewards of legal remedies for victims
      of domestic violence and sexual assault. Missing from this debate, however, is an
      analysis of the social incentives for victim advocates to offer legal options to
      their clients. Preliminary findings show that victim advocates perceive that
      outsiders respect legal work more than their care work with clients (listening,
      caring, and empathizing). This study offers three explanations for this
      phenomenon: (1) the devaluation of women's care work in general, (2) the
      confidentiality constraints on communicating the value of their care work, and
      (3) popular assumptions that care work requires professional credentials in order
      to be legitimate.

PMID- 22410772
TI  - Leaving ? moving: housing patterns of women who have left an abusive partner.
AB  - Access to safe and affordable housing is a key concern for women leaving abusive
      partners. Yet little is known about women's housing patterns around leaving. In
      this community sample, approximately equal numbers of women did not move, moved
      once, and moved two or more times during the transition period around leaving.
      Overall, moving patterns were associated with housing type and suitability,
      economic circumstances, and severity of violence. This study calls into question
      the tendency to equate leaving with moving, draws attention to the different
      housing patterns after leaving, and highlights the need to tailor housing
      supports to diverse women.

PMID- 22410773
TI  - Surviving the storm: the role of social support and religious coping in sexual
      assault recovery of African American women.
AB  - African American women are at high risk for sexual assault. In addition, many
      African American women endorse the use of social support and religiosity to cope
      with trauma. The current study investigates the relationship between these two
      coping strategies and posttrauma symptoms in a sample of 413 African American
      female sexual assault survivors using confirmatory factor analysis and structural
      equation modeling. Findings indicated that survivors with greater social support
      were less likely to endorse the symptoms of depression and PTSD. Conversely,
      increased use of religious coping was related to greater endorsement of
      depression and PTSD symptoms. Counseling and research implications are explored.

PMID- 22410774
TI  - Gender-based violence against civilian women in postinvasion Iraq:
      (re)politicizing George W. Bush's silent legacy.
AB  - This article explores the increase in gender-based violence against civilian
      women in Iraq since 2003 and connects it to the U.S.-led invasion of that
      country. It outlines the complex nature of the gender-based violence and the
      impact that it has had on civilian women in Iraq. It then analyzes the links
      between this violence and the politics of the postinvasion period. This article
      also explores how this violence has been politicized. Ultimately, the article
      (re)politicizes gender-based violence through a feminist lens and argues that the
      security of Iraq's women is fundamental to the stability of Iraq as a whole.

PMID- 22410776
TI  - The WRN and MUS81 proteins limit cell death and genome instability following
      oncogene activation.
AB  - Oncogene-induced replication stress is recognized as the primary cause of
      accumulation of DNA damage and genome instability in precancerous cells. Although
      the molecular mechanisms responding to such type of replication perturbation are
      not fully characterized, it has been speculated that their dysfunction may
      enhance genome instability and accelerate tumor progression. Here, we show that
      the WRN protein, a member of the human RecQ helicases, is necessary to sustain
      replication fork progression in response to oncogene-induced replication stress.
      Loss of WRN affects cell cycle progression and results in enhanced accumulation
      of double-strand breaks and instability at common fragile sites in cells
      experiencing oncogene-induced replication stress. Moreover, we demonstrate that
      double-strand breaks, observed upon oncogene over-expression, depend on the MUS81
      endonuclease, which represents a parallel pathway collaborating with WRN to
      prevent cell death. Overall, our findings give insights into the mechanisms
      protecting replication forks in cells experiencing oncogene-induced replication
      stress, and identify factors that, when mutated or dysfunctional, may enhance
      genome instability in precancerous cells. In addition, because concomitant
      depletion of WRN and MUS81 causes synthetic sickness in cells growing under
      oncogene-induced replication stress, our results support the possibility of
      targeting cancer cells with an impaired replication fork recovery pathway by a
      specific inactivation of the other parallel pathway.

PMID- 22410775
TI  - The receptor tyrosine kinase Axl is an essential regulator of prostate cancer
      proliferation and tumor growth and represents a new therapeutic target.
AB  - Deregulation of the receptor tyrosine kinase Axl has been implicated in the
      progression of several human cancers. However, the role of Axl in prostate cancer
      remains poorly understood, and the therapeutic efficacy of Axl targeting remains
      untested. In this report we identified Axl as a new therapeutic target for
      prostate cancer. Axl is consistently overexpressed in prostate cancer cell lines
      and human prostate tumors. Interestingly, the blockage of Axl gene expression
      strongly inhibits proliferation, migration, invasion and tumor growth.
      Furthermore, inhibition of Axl expression by small interfering RNA regulates a
      transcriptional program of genes involved in cell survival, strikingly all
      connected to the nuclear factor-kappaB pathway. Additionally, blockage of Axl
      expression leads to inhibition of Akt, IKKalpha and IkappaBalpha phosphorylation,
      increasing IkappaBalpha expression and stability. Furthermore, induction of Akt
      phosphorylation by insulin-like growth factor 1 in Axl knockdown cells restores
      Akt activity and proliferation. Taken together, our results establish an
      unambiguous role for Axl in prostate cancer tumorigenesis with implications for
      prostate cancer treatment.

PMID- 22410777
TI  - The role of TRKA signaling in IL-10 production by apoptotic tumor cell-activated
      macrophages.
AB  - Tumor-associated macrophages (TAMs) are a major supportive component within
      neoplasms. Mechanisms of macrophage (MPhi) attraction and differentiation to a
      tumor-promoting phenotype, which is characterized by pronounced interleukin (IL)
      10 production, are under investigation. We report that supernatants of dying
      cancer cells induced substantial IL-10 release from primary human MPhis,
      dependent on signaling through tyrosine kinase receptor A (TRKA or neurotrophic
      tyrosine kinase receptor type 1 (NTRK1)). Mechanistically, sphingosine-1
      phosphate (S1P) release from apoptotic cancer cells triggered src-dependent
      shuttling of cytosolic TRKA to the plasma membrane via S1P receptor signaling.
      Plasma membrane-associated TRKA, which was activated by constitutively autocrine
      secreted nerve growth factor, used phosphatidylinositol 3-kinase (PI3K)/AKT and
      p38 mitogen-activated protein kinase (MAPK) signaling to induce IL-10.
      Interestingly, TRKA-dependent signaling was required for cytokine production by
      TAMs isolated from primary murine breast cancer tissue. Besides IL-10, this
      pathway initiated secretion of IL-6, tumor necrosis factor-alpha (TNF-alpha) and
      monocyte chemotactic protein-1 (MCP-1), indicating relevance in cancer-associated
      inflammation. Our findings highlight a fine-tuned regulatory system including S1P
      dependent TRKA trafficking for executing TAM-like cell function in vitro as well
      as in vivo.

PMID- 22410778
TI  - Oncogenic K-ras expression is associated with derangement of the cAMP/PKA pathway
      and forskolin-reversible alterations of mitochondrial dynamics and respiration.
AB  - The Warburg effect in cancer cells has been proposed to involve several
      mechanisms, including adaptation to hypoxia, oncogenes activation or loss of
      oncosuppressors and impaired mitochondrial function. In previous papers, it has
      been shown that K-ras transformed mouse cells are much more sensitive as compared
      with normal cells to glucose withdrawal (undergoing apoptosis) and present a high
      glycolytic rate and a strong reduction of mitochondrial complex I. Recent
      observations suggest that transformed cells have a derangement in the cyclic
      adenosine monophosphate/cAMP-dependent protein kinase (cAMP/PKA) pathway, which
      is known to regulate several mitochondrial functions. Herein, the derangement of
      the cAMP/PKA pathway and its impact on transformation-linked changes of
      mitochondrial functions is investigated. Exogenous stimulation of PKA activity,
      achieved by forskolin treatment, protected K-ras-transformed cells from apoptosis
      induced by glucose deprivation, enhanced complex I activity, intracellular
      adenosine triphosphate (ATP) levels, mitochondrial fusion and decreased
      intracellular reactive oxygen species (ROS) levels. Several of these effects were
      almost completely prevented by inhibiting the PKA activity. Short-time treatment
      with compounds favoring mitochondrial fusion strongly decreased the cellular ROS
      levels especially in transformed cells. These findings support the notion that
      glucose shortage-induced apoptosis, specific of K-ras-transformed cells, is
      associated to a derangement of PKA signaling that leads to mitochondrial complex
      I decrease, reduction of ATP formation, prevalence of mitochondrial fission over
      fusion, and thereby opening new approaches for development of anticancer drugs.

PMID- 22410779
TI  - SIRT1 deacetylase promotes acquisition of genetic mutations for drug resistance
      in CML cells.
AB  - BCR-ABL transforms bone marrow progenitor cells and promotes genome instability,
      leading to development of chronic myelogenous leukemia (CML). The tyrosine kinase
      inhibitor imatinib effectively treats CML, but acquired resistance can develop
      because of BCR-ABL mutations. Mechanisms for acquisition of BCR-ABL mutations are
      not fully understood. Using a novel culture model of CML acquired resistance, we
      show that inhibition of SIRT1 deacetylase by small molecule inhibitors or gene
      knockdown blocks acquisition of BCR-ABL mutations and relapse of CML cells on
      tyrosine kinase inhibitors. SIRT1 knockdown also suppresses de novo genetic
      mutations of hypoxanthine phosphoribosyl transferase gene in CML and non-CML
      cells upon treatment with DNA damaging agent camptothecin. Although SIRT1 can
      enhance cellular DNA damage response, it alters functions of DNA repair
      machineries in CML cells and stimulates activity of error-prone DNA damage
      repair, in association with acquisition of genetic mutations. These results
      reveal a previously unrecognized role of SIRT1 for promoting mutation acquisition
      in cancer, and have implication for targeting SIRT1 to overcome CML drug
      resistance.

PMID- 22410780
TI  - N-cadherin regulates mammary tumor cell migration through Akt3 suppression.
AB  - N-cadherin is a cell-cell adhesion molecule that plays a role in breast cancer
      metastasis. Here, we show that in vivo expression of N-cadherin in the PyMT mouse
      model, which enhances mammary tumor metastasis, results in selective inhibition
      of Akt3 expression and phosphorylation. Similarly, exogenous expression of N
      cadherin in PyMT or MCF-7 mammary tumor cells enhanced cell motility and caused a
      dramatic reduction in Akt3 expression and phosphorylation. Moreover, knockdown of
      Akt3 in PyMT tumor cells increased cell motility and disrupted mammary
      morphogenesis, but had no effect on cell proliferation. Conversely,
      overexpression of wild-type Akt3 in PyMT-N-cadherin cells inhibited cell motility
      promoted by N-cadherin. Taken altogether, these findings demonstrate that N
      cadherin suppresses Akt3 to promote cell motility and highlight the intricate
      regulation of Akt isoforms by N-cadherin during metastasis.

PMID- 22410781
TI  - MiR-520h-mediated FOXC2 regulation is critical for inhibition of lung cancer
      progression by resveratrol.
AB  - Resveratrol, a phytochemical found in various plants and Chinese herbs, is
      associated with multiple tumor-suppressing activities, has been tested in
      clinical trials. However, the molecular mechanisms involved in resveratrol
      mediated tumor suppressing activities are not yet completely defined. Here, we
      showed that treatment with resveratrol inhibited cell mobility through induction
      of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also
      found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol
      mediated suppression of tumor metastasis in an in vitro and in vivo models. We
      also identified a signal cascade, namely, resveratrol-?miRNA-520h-?PP2A/C-?Akt ->
      NF-kappaB -> FOXC2, in which resveratrol inhibited the expression of FOXC2
      through regulation of miRNA-520h-mediated signal cascade. This study identified a
      new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor
      suppression activity and provide the clinical significances of miR-520h, PP2A/C
      and FOXC2 in lung cancer patients. Our results indicated a functional link
      between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability,
      and provide a new insight into the role of resveratrol-induced molecular and
      epigenetic regulations in tumor suppression.

PMID- 22410782
TI  - Raf activation by Ras and promotion of cellular metastasis require
      phosphorylation of prohibitin in the raft domain of the plasma membrane.
AB  - Prohibitin (PHB) is indispensable for Ras-induced Raf-1 activation, cell
      migration and growth; however, the exact role of PHB in the molecular
      pathogenesis of cancer metastasis remains largely unexamined. Here, we found a
      positive correlation between plasma membrane-associated PHB and the clinical
      stages of cancer. The level of PHB phosphorylated at threonine 258 (T258) and
      tyrosine 259 (Y259) in human cancer-cell membranes correlated with the
      invasiveness of cancer cells. Overexpression of phosphorylated PHB (phospho-PHB)
      in the lipid-raft domain of the cell membrane enhanced cell migration/invasion
      through PI3K/Akt and Raf-1/ERK activation. It also enhanced epithelial
      mesenchymal transition, matrix metalloproteinase-2 activity and invasiveness of
      cancer cells in vitro. Immunoprecipitation analysis demonstrated that phospho-PHB
      associated with Raf-1, Akt and Ras in the membrane and was essential for the
      activation of Raf-1 signaling by Ras. Mice implanted with cancer cells stably
      overexpressing PHB in the plasma membrane showed enlarged cervical tumors,
      enhanced metastasis and shorter survival time compared with mice implanted with
      cancer cells without PHB overexpression. Dephosphorylation of PHB at T258 by site
      directed mutagenesis diminished the in vitro and in vivo effects of PHB. These
      results suggest that increase in phospho-PHB T258 in the raft domain of the
      plasma membrane has a role in the Ras-driven activation of PI3K/Akt and Raf-1/ERK
      signaling cascades and results in the promotion of cancer metastasis.

PMID- 22410783
TI  - Carcinogen-specific mutational and epigenetic alterations in INK4A, INK4B and p53
      tumour-suppressor genes drive induced senescence bypass in normal diploid
      mammalian cells.
AB  - Immortalization (senescence bypass) is a critical rate-limiting step in the
      malignant transformation of mammalian somatic cells. Human cells must breach at
      least two distinct senescence barriers to permit unfettered clonal evolution
      during cancer development: (1) stress- or oncogene-induced premature senescence
      (SIPS/OIS), mediated via the p16-Rb and/or ARF-p53-p21 tumour-suppressive
      pathways, and (2) replicative senescence triggered by telomere shortening. In
      contrast, because their telomerase is constitutively active, cells from small
      rodents possess only the SIPS/OIS barrier, and are therefore useful for studying
      SIPS/OIS bypass in isolation. Dermal fibroblasts from the Syrian hamster (SHD
      cells) are exceptionally resistant to spontaneous SIPS bypass, but it can be
      readily induced following exposure to a wide range of chemical and physical
      carcinogens. Here we show that a spectrum of carcinogen-specific mutational and
      epigenetic alterations involving the INK4A (p16), p53 and INK4B (p15) genes are
      associated with induced SIPS bypass. With ionizing radiation, immortalization is
      invariably accompanied by efficient biallelic deletion of the complete INK4/CDKN2
      locus. In comparison, SHD cells immortalized by the powerful polycyclic
      hydrocarbon carcinogen benzo(a)pyrene display transversion point mutations in the
      DNA-binding domain of p53 coupled with INK4 alterations such as loss of
      expression of p15. Epimutational silencing of p16 is the primary event associated
      with immortalization by nickel, a human non-genotoxic carcinogen. As SIPS/OIS
      bypass is a prerequisite for the immortalization of normal diploid human
      epithelial cells, our results with the SHD model will provide a basis for
      delineating combinations of key molecular changes underpinning this important
      event in human carcinogenesis.

PMID- 22410784
TI  - BioNetSim: a Petri net-based modeling tool for simulations of biochemical
      processes.
AB  - BioNetSim, a Petri net-based software for modeling and simulating biochemistry
      processes, is developed, whose design and implement are presented in this paper,
      including logic construction, real-time access to KEGG (Kyoto Encyclopedia of
      Genes and Genomes), and BioModel database. Furthermore, glycolysis is simulated
      as an example of its application. BioNetSim is a helpful tool for researchers to
      download data, model biological network, and simulate complicated biochemistry
      processes. Gene regulatory networks, metabolic pathways, signaling pathways, and
      kinetics of cell interaction are all available in BioNetSim, which makes modeling
      more efficient and effective. Similar to other Petri net-based softwares,
      BioNetSim does well in graphic application and mathematic construction. Moreover,
      it shows several powerful predominances. (1) It creates models in database. (2)
      It realizes the real-time access to KEGG and BioModel and transfers data to Petri
      net. (3) It provides qualitative analysis, such as computation of constants. (4)
      It generates graphs for tracing the concentration of every molecule during the
      simulation processes.

PMID- 22410785
TI  - Protein construct optimization: data sharing strategy.

PMID- 22410786
TI  - A phylum level analysis reveals lipoprotein biosynthesis to be a fundamental
      property of bacteria.
AB  - Bacterial lipoproteins are proteins that are post-translationally modified with a
      diacylglyceride at an N-terminal cysteine, which serves to tether these proteins
      to the outer face of the plasma membrane or to the outer membrane. This paper
      reviews recent insights into the enzymology of bacterial lipoprotein biosynthesis
      and localization. Moreover, we use bioinformatic analyses of bacterial
      lipoprotein signal peptide features and of the key biosynthetic enzymes to
      consider the distribution of lipoprotein biosynthesis at the phylum level. These
      analyses support the important conclusion that lipoprotein biosynthesis is a
      fundamental pathway utilized across the domain bacteria. Moreover, with the
      exception of a small number of sequences likely to derive from endosymbiont
      genomes, the enzymes of bacterial lipoprotein biosynthesis appear unique to
      bacteria, making this pathway an attractive target for the development of novel
      antimicrobials. Whilst lipoproteins with comparable signal peptide features are
      encoded in the genomes of Archaea, it is clear that these lipoproteins have a
      distinctive biosynthetic pathway that has yet to be characterized.

PMID- 22410787
TI  - Converted neural cells: induced to a cure?
AB  - Many neurodegenerative disorders such as Parkinson's disease (PD), amyotrophic
      lateral sclerosis (ALS) and others often occur as a result of progressive loss of
      structure or function of neurons. Recently, many groups were able to generate
      neural cells, either differentiated from induced pluripotent stem cells (iPSCs)
      or converted from somatic cells. Advances in converted neural cells have opened a
      new era to ease applications for modeling diseases and screening drugs. In
      addition, the converted neural cells also hold the promise for cell replacement
      therapy (Kikuchi et al., 2011; Krencik et al., 2011; Kriks et al., 2011; Nori et
      al., 2011; Rhee et al., 2011; Schwartz et al., 2012). Here we will mainly discuss
      most recent progress on using converted functional neural cells to treat
      neurological diseases and highlight potential clinical challenges and future
      perspectives.

PMID- 22410788
TI  - On-bead expression of recombinant proteins in an agarose gel matrix coated on a
      glass slide.
AB  - A system for expression and in situ display of recombinant proteins on a
      microbead surface is described. Biotinylated PCR products were immobilized on
      microbead surfaces, which were then embedded in a gel matrix and supplied with
      translation machinery and substrates. Upon the incubation of the gel matrix,
      target proteins encoded on the bead-immobilized DNA were expressed and captured
      on the same bead, thus allowing bead-mediated linkage of DNA and encoded
      proteins. The new method combines the simplicity and convenience of solid-phase
      separation of genetic information with the benefits of cell-free protein
      synthesis, such as instant translation of genetic information, unrestricted
      substrate accessibility and flexible assay configuration design.

PMID- 22410789
TI  - Functional inclusion bodies produced in bacteria as naturally occurring nanopills
      for advanced cell therapies.
AB  - Inclusion bodies (50-500 nm in diameter) produced in recombinant bacteria can be
      engineered to contain functional proteins with therapeutic potential. Upon
      exposure, these protein particles are efficiently internalized by mammalian cells
      and promote recovery from diverse stresses. Being fully biocompatible, inclusion
      bodies are a novel platform, as tailored nanopills, for sustained drug release in
      advanced cell therapies.

PMID- 22410790
TI  - Arabidopsis STO/BBX24 negatively regulates UV-B signaling by interacting with
      COP1 and repressing HY5 transcriptional activity.
AB  - UV-B (280-315 nm) is an integral part of solar radiation and can act either as a
      stress inducer or as a developmental signal. In recent years, increasing
      attention has been paid to the low-fluence UV-B-induced photomorphogenic response
      and several key players in this response have been identified, which include UVR8
      (a UV-B-specific photoreceptor), COP1 (a WD40-repeat-containing RING finger
      protein), HY5 (a basic zipper transcription factor), and RUP1/2 (two UVR8
      interacting proteins). Here we report that Arabidopsis SALT TOLERANCE
      (STO/BBX24), a known regulator for light signaling in plants, defines a new
      signaling component in UV-B-mediated photomorphogenesis. The bbx24 mutant is
      hypersensitive to UV-B radiation and becomes extremely dwarfed under UV-B
      treatment. By contrast, BBX24 overexpression transgenic lines respond much more
      weakly to UV-B than the bbx24 and wild-type plants. BBX24 expression is UV-B
      inducible and its accumulation under UV-B requires COP1. Co-immunoprecipitation
      experiments indicate that BBX24 interacts with COP1 in planta upon UV-B
      illumination. Moreover, BBX24 interacts with HY5 and acts antagonistically with
      HY5 in UV-B-induced inhibition of hypocotyl elongation. Furthermore, BBX24
      attenuates UV-B-induced HY5 accumulation and suppresses its transcription
      activation activity. Taken together, our results reveal a previously
      uncharacterized function of the light-regulated BBX24 in UV-B responses and
      demonstrate that BBX24 functions as a negative regulator of photomorphogenic UV-B
      responses by interacting with both COP1 and HY5. The UV-B-inducible expression
      pattern and its suppression of HY5 activity suggest that BBX24 could be a new
      component of the feedback regulatory module of UV-B signaling in plants.

PMID- 22410791
TI  - Essential role of Fbxl14 ubiquitin ligase in regulation of vertebrate axis
      formation through modulating Mkp3 level.

PMID- 22410792
TI  - Gating neural development and aging via nuclear pores.
AB  - Emerging evidence suggests an involvement of nuclear pore components in the
      regulation of neural differentiation and aging. These findings will have far
      ranging impacts on the understanding of the function of the nuclear envelope in
      physiological settings and in various neurological diseases.

PMID- 22410793
TI  - Akt is negatively regulated by the MULAN E3 ligase.
AB  - The serine/threonine kinase Akt functions in multiple cellular processes,
      including cell survival and tumor development. Studies of the mechanisms that
      negatively regulate Akt have focused on dephosphorylation-mediated inactivation.
      In this study, we identified a negative regulator of Akt, MULAN, which possesses
      both a RING finger domain and E3 ubiquitin ligase activity. Akt was found to
      directly interact with MULAN and to be ubiquitinated by MULAN in vitro and in
      vivo. Other molecular assays demonstrated that phosphorylated Akt is a
      substantive target for both interaction with MULAN and ubiquitination by MULAN.
      The results of the functional studies suggest that the degradation of Akt by
      MULAN suppresses cell proliferation and viability. These data provide insight
      into the Akt ubiquitination signaling network.

PMID- 22410794
TI  - Self-eating with your fingers.

PMID- 22410795
TI  - Regulation of small RNA stability: methylation and beyond.
AB  - As central components of RNA silencing, small RNAs play diverse and important
      roles in many biological processes in eukaryotes. Aberrant reduction or elevation
      in the levels of small RNAs is associated with many developmental and
      physiological defects. The in vivo levels of small RNAs are precisely regulated
      through modulating the rates of their biogenesis and turnover. 2'-O-methylation
      on the 3' terminal ribose is a major mechanism that increases the stability of
      small RNAs. The small RNA methyltransferase HUA ENHANCER1 (HEN1) and its homologs
      methylate microRNAs and small interfering RNAs (siRNAs) in plants, Piwi
      interacting RNAs (piRNAs) in animals, and siRNAs in Drosophila. 3' nucleotide
      addition, especially uridylation, and 3'-5' exonucleolytic degradation are major
      mechanisms that turnover small RNAs. Other mechanisms impacting small RNA
      stability include complementary RNAs, cis-elements in small RNA sequences and RNA
      binding proteins. Investigations are ongoing to further understand how small RNA
      stability impacts their accumulation in vivo in order to improve the utilization
      of RNA silencing in biotechnology and therapeutic applications.

PMID- 22410796
TI  - Is it the right time to subject children with acute kidney injury to rasburicase
      trials?

PMID- 22410797
TI  - Atypical hemolytic uremic syndrome in children: complement mutations and clinical
      characteristics.
AB  - BACKGROUND: Mutations in complement factor H (CFH), factor I (CFI), factor B
      (CFB), thrombomodulin (THBD), C3 and membrane cofactor protein (MCP), and
      autoantibodies against factor H (alphaFH) with or without a homozygous deletion
      in CFH-related protein 1 and 3 (?CFHR1/3) predispose development of atypical
      hemolytic uremic syndrome (aHUS). METHODS: Different mutations in genes encoding
      complement proteins in 45 pediatric aHUS patients were retrospectively linked
      with clinical features, treatment, and outcome. RESULTS: In 47% of the study
      participants, potentially pathogenic genetic anomalies were found (5xCFH, 4xMCP,
      and 4xC3, 3xCFI, 2xCFB, 6xalphaFH, of which five had ?CFHR1/3); four patients
      carried combined genetic defects or a mutation, together with alphaFH. In the
      majority (87%), disease onset was preceeded by a triggering event; in 25% of
      cases diarrhea was the presenting symptom. More than 50% had normal serum C3
      levels at presentation. Relapses were seen in half of the patients, and there was
      renal graft failure in all except one case following transplant. CONCLUSIONS:
      Performing adequate DNA analysis is essential for treatment and positive outcome
      in children with aHUS. The impact of intensive initial therapy and renal
      replacement therapy, as well as the high risk of recurrence of aHUS in renal
      transplant, warrants further understanding of the pathogenesis, which will lead
      to better treatment options.

PMID- 22410798
TI  - Elevated urine levels of heparin-binding protein in children with urinary tract
      infection.
AB  - BACKGROUND: Urinary tract infection (UTI) is a common infection diagnosis in
      children, and efficient diagnosis and treatment are important to avoid serious
      complications. In this study we investigated whether urinary levels of neutrophil
      derived heparin-binding protein (HBP) can be used as a marker of UTI in children.
      These results were compared to those of dipstick analysis, interleukin-6 (IL-6)
      analysis in urine, and bacterial culturing. METHODS: Seventy-eight children aged
      0-18 years with fever and/or symptoms indicating UTI were enrolled in a
      prospective consecutive study. Urine samples were cultured and analyzed with
      dipstick, and concentrations of HBP and IL-6 were measured. RESULTS: Fifteen
      patients were classified as having UTI, 30 patients had fever but were diagnosed
      with a non-urinary tract infection, and 33 patients had neither UTI nor fever.
      Using a urine HBP (U-HBP) cut-off level of 32 ng/mL, the sensitivity and
      specificity for detecting UTI were 93.3 and 90.3 %, respectively. Receiver
      operating characteristic curves demonstrated that U-HBP levels were a higher
      specificity indicator of UTI than urine white blood cell counts or urine IL-6
      levels; they also showed a higher sensitivity than the results of the urine
      nitrite test. All patients with significant growth of clinically relevant
      bacteria had elevated U-HBP levels. CONCLUSION: The results indicate that rapid
      analysis of U-HBP can provide helpful guidance in the management of children with
      suspected UTI.

PMID- 22410799
TI  - Unilateral multicystic dysplastic kidney: does initial size matter?
AB  - BACKGROUND: We report the long-term follow-up of children with antenatally
      detected unilateral multicystic dysplastic kidney (MCDK) who were followed
      between 1985 and 2009. METHODS: Involution rates were documented over time based
      on the initial size of the MCDK, as documented on postnatal ultrasound (USS), as
      well as long-term complications and renal function. RESULTS: In 323 patients (182
      male), 10 % of MCDK had involuted, as evidenced on the first postnatal USS, with
      survival function analysis showing the probability of complete involution to be
      35 % in 249 patients by 2 years of age, 47 % in 180 patients by 5 years of age
      and 62 % in 94 patients by 10 years of age. There was a significant difference in
      the involution rates of MCKD at the 10-year follow-up between MCDK with an
      initial size of >5 cm versus MCDK with an initial size of <=5 cm (p < 0.0001). No
      patients in the whole cohort developed sustained hypertension or malignancy
      during a median follow-up of 10.1 years (range 0.3-15.4 years). Median estimated
      glomerular filtration rate (eGFR) in 76 patients (7 at 5 years, 69 at 10 years)
      was 93 ml/min/1.73 m(2) (range 46-175 ml/min/1.73 m(2)), with 40 (53%) having an
      eGFR of between 90 and 140 ml/min/1.73 m(2). Twenty-three (30 %) of the 76
      patients at 10 years had normal eGFR (90-140 ml/min/1.73 m(2)) as well as
      complete involution of the MCDK, compensatory hypertrophy of the contralateral
      kidney, no proteinuria and no hypertension. CONCLUSIONS: Larger MCDK at birth are
      less likely to involute during the first decade of life. However, conservative
      management remains justified due to the lack of complications. A minority of
      patients fulfil current criteria for discharge from specialty follow-up at 10
      years.

PMID- 22410800
TI  - Second-line chemotherapy for advanced gastric cancer in Korea.
AB  - Stomach cancer is still one of the most prevalent malignancies and is the main
      cause of cancer deaths worldwide. The outcome for patients with metastasis, as
      well as for those with tumor recurrence, is dismal, with median survival time not
      greater than a year. Patients with unresectable locally advanced or metastatic
      lesions have been treated with systemic chemotherapy, and several randomized
      studies have demonstrated the benefit of chemotherapy compared with best
      supportive care. Recently, randomized phase III trials have presented a benefit
      of second-line chemotherapy compared with supportive care alone. However, it is
      not known at present which drug is the most effective in this setting. In Korea,
      the practice of offering second-line treatment to patients with advanced gastric
      cancer (AGC) is common, and many prospective clinical trials investigating
      clinical outcomes of second-line chemotherapy have been reported. Therefore, to
      define the potential role of second-line chemotherapy and to help to select an
      effective regimen, we review the published Korean prospective data concerning the
      use of chemotherapy in the second-line setting for the treatment of AGC. No phase
      III trials but 20 phase II trials were identified. The benefit of second-line
      chemotherapy in AGC has indirect evidence considering prolongation of progression
      free survival (PFS) and improvement of the response rate. Taxanes, irinotecan,
      and oxaliplatin have been studied much and might be promising drugs considering
      cross-resistance to a 5-fluorouracil and cisplatin combination (FP). A large,
      prospective, multicenter, randomized phase III study is warranted to select the
      most effective second-line chemotherapeutic agents.

PMID- 22410802
TI  - Emerging technologies for patient-specific healthcare.

PMID- 22410801
TI  - HER2 expression and its clinicopathological features in resectable gastric
      cancer.
AB  - BACKGROUND: A recent randomized controlled trial (Trastuzumab for Gastric Cancer
      [ToGA] study) established standard scoring criteria of human epidermal growth
      factor receptor 2 (HER2) for gastric cancer and demonstrated the efficacy of
      trastuzumab for treating metastatic gastric cancer. The aim of the present study
      was to evaluate the frequency of HER2-positive cases by application of the
      standard criteria in patients with resectable gastric cancer and to examine the
      relationships between HER2 expression and prognosis, mucin phenotype, p53 status,
      and clinicopathological features. METHODS: A total of 213 patients were included
      in this retrospective study. All tumor samples were examined for HER2 expression
      by immunohistochemistry (IHC), HER2 amplification by in situ hybridization, and
      mucin and p53 expression by staining for CD10, MUC2, MUC5AC, MUC6, and p53.
      RESULTS: HER2-positive tumors were identified in 25 patients (11.7 %). HER2
      positive cases were more frequently found in men, older patients, and in the
      intestinal histological type (P = 0.0048, 0.0309, and <0.0001, respectively).
      Although no association was found between HER2 overexpression and mucin
      phenotype, the expression of CD10 and p53 was significantly correlated with HER2
      positivity (P = 0.0079 and 0.013). The overall survival of HER2-negative and 
      positive patients was not significantly different. However, in patients with
      stage III/IV, overall survival was worse in HER2-positive patients (P = 0.0149).
      In a comparison between dual-color in situ hybridization (DISH) and fluorescence
      in situ hybridization (FISH), four IHC2+/3+ cases that were DISH-positive were
      judged as negative by FISH. CONCLUSIONS: Our study indicated that HER2 expression
      was less frequent in resectable gastric cancer than in metastatic gastric cancer.
      The impact of HER2 expression on survival was limited. DISH was superior to FISH
      for evaluating cases with limited HER2 expression.

PMID- 22410803
TI  - Cardiovascular drift during heat stress:  implications for exercise prescription.
AB  - Cardiovascular drift, the progressive increase in heart rate and decrease in
      stroke volume that begins after approximately 10 min of prolonged moderate
      intensity exercise, is associated with decreased maximal oxygen uptake,
      particularly during heat stress. Consequently, the increased heart rate reflects
      an increased relative metabolic intensity during prolonged exercise in the heat
      when cardiovascular drift occurs, which has implications for exercise
      prescription.

PMID- 22410804
TI  - Novel tubulin polymerization inhibitors overcome multidrug resistance and reduce
      melanoma lung metastasis.
AB  - PURPOSE: To evaluate abilities of 2-aryl-4-benzoyl-imidazoles (ABI) to overcome
      multidrug resistance (MDR), define their cellular target, and assess in vivo
      antimelanoma efficacy. METHODS: MDR cell lines that overexpressed P-glycoprotein,
      MDR-associated proteins, and breast cancer resistance protein were used to
      evaluate ABI ability to overcome MDR. Cell cycle analysis, molecular modeling,
      and microtubule imaging were used to define ABI cellular target. SHO mice bearing
      A375 human melanoma xenograft were used to evaluate ABI in vivo antitumor
      activity. B16-F10/C57BL mouse melanoma lung metastasis model was used to test ABI
      efficacy to inhibit tumor lung metastasis. RESULTS: ABIs showed similar potency
      to MDR cells compared to matching parent cells. ABIs were identified to target
      tubulin on the colchicine binding site. After 31 days of treatment, ABI-288 dosed
      at 25 mg/kg inhibited melanoma tumor growth by 69%; dacarbazine at 60 mg/kg
      inhibited growth by 52%. ABI-274 dosed at 25 mg/kg showed better lung metastasis
      inhibition than dacarbazine at 60 mg/kg. CONCLUSIONS: This new class of
      antimitotic compounds can overcome several clinically important drug resistant
      mechanisms in vitro and are effective in inhibiting melanoma lung metastasis in
      vivo, supporting their further development.

PMID- 22410805
TI  - Sciatic nerve tumor and tumor-like lesions - uncommon pathologies.
AB  - Sciatic nerve mass-like enlargement caused by peripheral nerve sheath tumors or
      neurocutaneous syndromes such as neurofibromatosis or schwannomatosis has been
      widely reported. Other causes of enlargement, such as from perineuroma,
      fibromatosis, neurolymphoma, amyloidosis, endometriosis, intraneural ganglion
      cyst, Charcot-Marie-Tooth disease, and chronic inflammatory demyelinating
      polyneuropathy are relatively rare. High-resolution magnetic resonance imaging
      (MRI) is an excellent non-invasive tool for the evaluation of such lesions. In
      this article, the authors discuss normal anatomy of the sciatic nerve and MRI
      findings of the above-mentioned lesions.

PMID- 22410806
TI  - First-principles studies of BN sheets with absorbed transition metal single atoms
      or dimers: stabilities, electronic structures, and magnetic properties.
AB  - BN sheets with absorbed transition metal (TM) single atoms, including Fe, Co, and
      Ni, and their dimers have been investigated by using a first-principles method
      within the generalized gradient approximation. All of the TM atoms studied are
      found to be chemically adsorbed on BN sheets. Upon adsorption, the binding
      energies of the Fe and Co single atoms are modest and almost independent of the
      adsorption sites, indicating the high mobility of the adatoms and isolated
      particles to be easily formed on the surface. However, Ni atoms are found to bind
      tightly to BN sheets and may adopt a layer-by-layer growth mode. The Fe, Co, and
      Ni dimers tend to lie (nearly) perpendicular to the BN plane. Due to the wide
      band gap of the pure BN sheet, the electronic structures of the BN sheets with TM
      adatoms are determined primarily by the distribution of TM electronic states
      around the Fermi level. Very interesting spin gapless semiconductors or half
      metals can be obtained in the studied systems. The magnetism of the TM atoms is
      preserved well on the BN sheet, very close to that of the corresponding free
      atoms and often weakly dependent on the adsorption sites. The present results
      indicate that BN sheets with adsorbed TM atoms have potential applications in
      fields such as spintronics and magnetic data storage due to the special spin
      polarized electronic structures and magnetic properties they possess.

PMID- 22410807
TI  - Evaluating the biodegradability of Gelatin/Siloxane/Hydroxyapatite (GS-Hyd)
      complex in vivo and its ability for adhesion and proliferation of rat bone marrow
      mesenchymal stem cells.
AB  - Recent studies have shown that the use of biomaterials and new biodegradable
      scaffolds for repair or regeneration of damaged tissues is of vital importance.
      Scaffolds used in tissue engineering should be biodegradable materials with three
      dimensional structures which guide the growth and differentiation of the cells.
      They also tune physical, chemical and biological properties for efficient
      supplying of the cells to the selected tissues and have proper porosity along
      with minimal toxic effects. In this manner, the study of these characteristics is
      a giant stride towards scaffold design. In this study,
      Gelatin/Siloxane/Hydroxyapatite (GS-Hyd) scaffold was synthesized and its
      morphology, in vivo biodegradability, cytotoxic effects and ability for cell
      adhesion were investigated using mesenchymal stem cells (MSCs). The cells were
      treated with different volumes of the scaffold suspension for evaluation of its
      cytotoxic effects. The MSCs were also seeded on scaffolds and cultured for 2
      weeks to evaluate the ability of the scaffold in promoting of cell adhesion and
      growth. To check the biodegradability of the scaffold in vivo, scaffolds were
      placed in the rat body for 21 days in three different positions of thigh muscle,
      testicle, and liver and they were analyzed by scanning electron microscopy (SEM)
      and weight changes. According to the results of the viability of this study, no
      cytotoxic effects of GS-Hyd scaffold was found on the cells and MSCs could adhere
      on the scaffold with expanding their elongations and forming colonies. The rate
      of degradation as assessed by weight loss was significant within each group along
      with significant differences between different tissues at the same time point.
      SEM micrographs also indicated the obvious morphological changes on the surface
      of the particles and diameter of the pores through different stages of
      implantation. The greatest amount of degradation happened to the scaffold
      particles implanted into the muscle, followed by testicle and liver,
      respectively.

PMID- 22410808
TI  - Human amniotic fluid-derived c-kit(+) and c-kit (-) stem cells: growth
      characteristics and some differentiation potential capacities comparison.
AB  - Amniotic fluid (AF) contains heterogeneous and multipotential cell types. A pure
      mesenchymal stem cells group can be sorted from AF using flow cytometry. In order
      to evaluate a possible therapeutic application of these cells, the human AF
      derived c-kit(+) stem cells (c-kit(+) AFS) were compared with the c-kit(-)
      (unselected) stem cells (c-kit(-) AFS). Our findings revealed that the optimal
      period to obtain c-kit(+) AFS cells was between 16 and 22 weeks of gestation.
      Following cell sorting, c-kit(+) AFS cells shared similar morphological and
      proliferative characteristics as the c-kit(-) AFS cells. Both c-kit(+) and c-kit(
      ) AFS cells had the characteristics of mesenchymal stem cells through surface
      marker identification by flow cytometric and immunocytochemical analysis. Both c
      kit(+) and c-kit(-) AFS cells could differentiate along adipogenic and osteogenic
      lineages. However, the myocardial differentiation capacity was enhanced in c
      kit(+) AFS cells by detecting GATA-4, cTnT, alpha-actin, Cx43 mRNA and protein
      expression after myocardial induction; whereas induced c-kit(-) AFS cells were
      only detected with GATA-4 mRNA and protein expression. The c-kit(+) AFS cells
      could have potential clinical application for myogenesis in cardiac regenerative
      therapy.

PMID- 22410809
TI  - Association of PPAR-gamma gene polymorphisms with obesity and obesity-associated
      phenotypes in North Indian population.
AB  - OBJECTIVES: The worldwide increasing prevalence of obesity is considered as a
      major health problem. Peroxisome proliferator-activated receptor gamma (PPAR
      gamma) controls adipocyte differentiation and regulates a number of genes
      associated with energy homeostasis. In this study, we investigated the
      association of PPAR-gamma gene Pro12Ala (rs1801282) and C1431T (rs3856806)
      polymorphisms with morbid obesity and related phenotypes, in north Indian
      population. METHODS: A total of 6,42 subjects, 309, obese and 333 nonobese
      individuals were included in this case-control study. Insulin, adiponectin,
      glucose, and lipid levels were estimated using standard protocols. All subjects
      were genotyped by PCR restriction fragment length polymorphism (PCR-RFLP) method.
      RESULTS: The ProAla+AlaAla genotypes of PPAR-gamma Pro12Ala were significantly
      associated with higher risk of obesity while C1431T polymorphism did not show any
      significant association. None of the haplotypes showed association with morbid
      obesity. However, a strong association of variant genotypes was observed with
      higher levels of insulin, HOMA-IR, and lower serum adiponectin concentrations.
      CONCLUSION: PPAR-gamma gene polymorphisms influence obesity and obesity phenotype
      in a complex manner, probably involving insulin resistance in north Indian
      population.

PMID- 22410810
TI  - Circulating 25-hydroxyvitamin D concentrations are correlated with
      cardiometabolic risk among American black and white adolescents living in a year
      round sunny climate.
AB  - OBJECTIVE: Low vitamin D status is common among healthy black and white
      adolescents residing at southern U.S. latitudes with a year-round sunny climate.
      Thus we aimed to study the relationships between circulating 25-hydroxyvitamin D
      [25(OH)D] and cardiometabolic risk factors in this population. RESEARCH DESIGN
      AND METHODS: 25(OH)D concentrations were measured with liquid chromatography
      tandem mass spectroscopy in 701 girls and boys (14-18 years old, 54% blacks, 49%
      females). Cardiometabolic risk was indexed by adipokines, inflammatory markers,
      fasting glucose, homeostatic model assessment-insulin resistance (HOMA-IR), lipid
      profile, and blood pressure (BP). RESULTS: Controlling for age, sex, race, sexual
      maturation, season, physical activity, and percent body fat, 25(OH)D
      concentrations were significantly correlated with adiponectin (r = 0.06, P =
      0.05), leptin (r = -0.32, P < 0.01), fibrinogen (r = -0.05, P = 0.03), glucose (r
      = -0.16, P = 0.02), HOMA-IR (r = -0.17, P < 0.01), HDL cholesterol (r = 0.14, P =
      0.02), systolic BP (r = -0.10, P = 0.02), and diastolic BP (r = -0.21, P < 0.01).
      When 25(OH)D concentrations were stratified into increasing tertiles, there were
      significant linear upward trends for adiponectin (P = 0.01) and HDL cholesterol
      (P = 0.04), but significant linear down trends for glucose (P < 0.01), HOMA-IR (P
      < 0.01), and systolic BP (P < 0.01), after adjusting for the above covariates.
      CONCLUSIONS: Circulating 25(OH)D concentrations are associated with various
      adverse cardiometabolic risk factors, independent of adiposity. Clinical trials
      addressing the effects of vitamin D supplementation on cardiometabolic risk are
      warranted in adolescents irrespective of their geographical regions.

PMID- 22410811
TI  - Whole-blood tissue factor procoagulant activity is elevated in type 1 diabetes:
      effects of hyperglycemia and hyperinsulinemia.
AB  - OBJECTIVE: To determine tissue factor procoagulant activity (TF-PCA) in patients
      with type 1 diabetes and to examine effects of hyperglycemia and hyperglycemia
      plus hyperinsulinemia on TF-PCA. RESEARCH DESIGN AND METHODS: We have determined
      circulating TF-PCA and other coagulation factors under basal (hyperglycemic)
      conditions, after acute correction of hyperglycemia, in response to 24 h of
      selective hyperglycemia, and in response to 24 h of hyperglycemia plus
      hyperinsulinemia in nine type 1 diabetic patients and in seven nondiabetic
      control subjects. RESULTS: As shown previously in patients with type 2 diabetes,
      basal TF-PCA and plasma coagulation factor VIIa (FVIIa) were higher in patients
      with type 1 diabetes than in nondiabetic control subjects. However, in contrast
      with type 2 diabetes, normalizing glucose did not decrease the elevated TF-PCA
      levels, and raising glucose or glucose plus insulin levels did not increase TF
      PCA. CONCLUSIONS: Patients with type 1 diabetes have elevated circulating TF-PCA
      and FVIIa levels and are in a procoagulant state that may predispose them to
      acute cardiovascular events. The mechanisms regulating TF-PCA in patients with
      type 1 and type 2 diabetes are different and should be further explored.

PMID- 22410812
TI  - Association of diabetes and HbA1c levels with gastrointestinal manifestations.
AB  - OBJECTIVE: To determine the prevalence of gastrointestinal (GI) manifestations
      associated with diabetes mellitus (DM) in a Taiwanese population undergoing
      bidirectional endoscopies. RESEARCH DESIGN AND METHODS: Subjects voluntarily
      undergoing upper endoscopy/colonoscopy as part of a medical examination at the
      National Taiwan University Hospital were recruited during 2009. Diagnosis of DM
      included past history of DM, fasting plasma glucose >= 126 mg/dL, or glycated
      hemoglobin (HbA(1c)) >= 6.5%. Comparisons were made between diabetic and
      nondiabetic subjects, subjects with lower and higher HbA(1c) levels, and diabetic
      subjects with and without complications, respectively, for their GI symptoms,
      noninvasive GI testing results, and endoscopic findings. RESULTS: Among 7,770
      study subjects, 722 (9.3%) were diagnosed with DM. The overall prevalence of GI
      symptoms was lower in DM subjects (30.3 vs. 35.4%, P = 0.006). In contrast, the
      prevalence of erosive esophagitis (34.3 vs. 28.6%, P = 0.002), Barrett's
      esophagus (0.6 vs. 0.1%, P = 0.001), peptic ulcer disease (14.8 vs. 8.5%, P <
      0.001), gastric neoplasms (1.8 vs. 0.7%, P = 0.003), and colonic neoplasms (26.6
      vs. 16.5%, P < 0.001) was higher in diabetic subjects. Diagnostic accuracy of
      immunochemical fecal occult blood test for colonic neoplasms was significantly
      decreased in DM (70.7 vs. 81.7%, P < 0.001). Higher HbA(1c) levels were
      associated with a decrease of GI symptoms and an increase of endoscopic
      abnormalities. Diabetic subjects with complications had a higher prevalence of
      colonic neoplasms (39.2 vs. 24.5%, P = 0.002) than those without. CONCLUSIONS: DM
      and higher levels of HbA(1c) were associated with lower prevalence of GI symptoms
      but higher prevalence of endoscopic abnormalities.

PMID- 22410813
TI  - Relationship between glycosylated hemoglobin assessment and glucose therapy
      intensification in patients with diabetes hospitalized for acute myocardial
      infarction.
AB  - OBJECTIVE: To evaluate the relationship between A1C and glucose therapy
      intensification (GTI) in patients with diabetes mellitus (DM) hospitalized for
      acute myocardial infarction (AMI). RESEARCH DESIGN AND METHODS: A1C was measured
      as part of routine care (clinical A1C) or in the core laboratory (laboratory A1C,
      results unavailable to clinicians). GTI predictors were identified using
      hierarchical Poisson regression. RESULTS: Of 1,274 patients, 886 (70%) had
      clinical A1C and an additional 263 had laboratory A1C measured. Overall, A1C was
      <7% in 419 (37%), 7-9% in 415 (36%), and >9% in 315 patients (27%). GTI occurred
      in 31% of patients and was more frequent in those with clinical A1C both before
      (34 vs. 24%, P < 0.001) and after multivariable adjustment (relative risk 1.34
      [95% CI 1.12-1.62] vs. no clinical A1C). CONCLUSIONS: Long-term glucose control
      is poor in most AMI patients with DM, but only a minority of patients undergo GTI
      at discharge. Inpatient A1C assessment is strongly associated with
      intensification of glucose-lowering therapy.

PMID- 22410814
TI  - The relationship between diabetes, metabolic syndrome, and platelet activity as
      measured by mean platelet volume: the National Health And Nutrition Examination
      Survey, 1999-2004.
AB  - OBJECTIVE: The association between platelet activity, diabetes, and
      glucometabolic control is uncertain. We aim to investigate mean platelet volume
      (MPV), a marker of platelet size and platelet activity, with the prevalence of
      diabetes, metabolic syndrome, and degree of glycemic control. RESEARCH DESIGN AND
      METHODS: This is a retrospective analysis of 13,021 participants in the National
      Health and Nutrition Examination Survey from 1999 to 2004. Prevalence of diabetes
      was defined as nonfasting glucose >200 mg/dL, fasting glucose >= 126 mg/dL, or
      treatment with hypoglycemic agents. Presence of metabolic syndrome was determined
      by the National Cholesterol Education Program Adult Treatment Panel III
      definition. Odds ratios and 95% CIs were estimated by logistic regression.
      RESULTS: MPV was significantly higher in subjects with diabetes (8.20 vs. 8.06
      femtoliter [fL], P < 0.01) but not in subjects with metabolic syndrome (8.09 vs.
      8.07 fL, P = 0.24). For the metabolic syndrome components, MPV was significantly
      higher in abdominal obesity (P = 0.03) and low HDL (P = 0.04), and not different
      in high blood pressure (P = 0.07), abnormal glucose metabolism (P = 0.71), or
      hypertriglyceridemia (P = 0.46). There was a significant correlation between MPV
      and glucose (P < 0.0001) and between MPV and hemoglobin A(1c) (P < 0.0001) in
      subjects with diabetes. These correlations were no longer significant in those
      without diabetes. The adjusted odds of diabetes rose with increasing MPV levels
      and were most pronounced in subjects with MPV levels exceeding the 90th
      percentile (>= 9.31 fL). The association between MPV and diabetes was most
      apparent in those with the poorest glucose control. CONCLUSIONS: Mean platelet
      volume is strongly and independently associated with the presence and severity of
      diabetes.

PMID- 22410815
TI  - Effects of diet soda on gut hormones in youths with diabetes.
AB  - OBJECTIVE: In patients with type 2 diabetes, but not type 1 diabetes, abnormal
      secretion of incretins in response to oral nutrients has been described. In
      healthy youths, we recently reported accentuated glucagon-like peptide 1 (GLP-1)
      secretion in response to a diet soda sweetened with sucralose and acesulfame-K.
      In this study, we examined the effect of diet soda on gut hormones in youths with
      diabetes. RESEARCH DESIGN AND METHODS: Subjects aged 12-25 years with type 1
      diabetes (n = 9) or type 2 diabetes (n = 10), or healthy control participants (n
      = 25) drank 240 mL cola-flavored caffeine-free diet soda or carbonated water,
      followed by a 75-g glucose load, in a randomized, cross-over design. Glucose, C
      peptide, GLP-1, glucose-dependent insulinotropic peptide (GIP), and peptide Tyr
      Tyr (PYY) were measured for 180 min. Glucose and GLP-1 have previously been
      reported for the healthy control subjects. RESULTS: GLP-1 area under the curve
      (AUC) was 43% higher after ingestion of diet soda versus carbonated water in
      individuals with type 1 diabetes (P = 0.020), similar to control subjects (34%
      higher, P = 0.029), but was unaffected by diet soda in patients with type 2
      diabetes (P = 0.92). Glucose, C-peptide, GIP, and PYY AUC were not statistically
      different between the two conditions in any group. CONCLUSIONS: Ingestion of diet
      soda before a glucose load augmented GLP-1 secretion in type 1 diabetic and
      control subjects but not type 2 diabetic subjects. GIP and PYY secretion were not
      affected by diet soda. The clinical significance of this increased GLP-1
      secretion, and its absence in youths with type 2 diabetes, needs to be
      determined.

PMID- 22410817
TI  - Substantial increase in incidence of severe hypoglycemia between 1997-2000 and
      2007-2010: a German longitudinal population-based study.
AB  - OBJECTIVE: To compare the incidences of severe hypoglycemia and corresponding
      clinical circumstances in a German population between 2007-2010 and 1997-2000.
      RESEARCH DESIGN AND METHODS: A screening for severe hypoglycemia was performed in
      the Lippe-Detmold area in Germany to sensitively detect severe hypoglycemia. This
      was defined as a symptomatic event requiring treatment with intravenous glucose
      and being confirmed by a blood glucose measurement of <50 mg/dL. RESULTS: Severe
      hypoglycemia increased considerably from 264 events in 1997-2000 to 495 events in
      2007-2010, which translated into an increase in frequency of severe hypoglycemia
      among all emergency admissions from 0.68 to 0.83% (P = 0.015). This was mostly
      related to intensification of antihyperglycemic therapy, particularly in the
      increasingly morbid group of hypoglycemic patients with type 2 diabetes indicated
      by lower HbA(1c), more comedication (3.3 vs. 7.7 drugs), and more concomitant
      diseases (3.6 vs. 4.4) (all P values <0.001). CONCLUSIONS: Within a 10-year
      period, there was an intensification of antihyperglycemic therapy in increasingly
      comorbid subjects, leading to a considerably higher incidence of severe
      hypoglycemia.

PMID- 22410816
TI  - Significance of urinary full-length and ectodomain forms of megalin in patients
      with type 2 diabetes.
AB  - OBJECTIVE: Megalin, an endocytic receptor in proximal tubule cells, is involved
      in the mechanisms of albuminuria in diabetic nephropathy (DN). To develop
      efficient novel biomarkers associated with the pathogenesis of DN, we
      investigated urinary megalin excretion in type 2 diabetes. RESEARCH DESIGN AND
      METHODS: Sandwich enzyme-linked immunosorbent assay systems were established with
      monoclonal antibodies against the NH(2) (amino [A]-megalin assay) and COOH (C
      megalin assay) termini of megalin to analyze urinary forms of megalin in 68
      patients with type 2 diabetes. RESULTS: The A-megalin assay mainly detected a
      megalin ectodomain form in the soluble urinary fraction, whereas the C-megalin
      assay identified a full-length form in both soluble and insoluble fractions.
      Urinary C-megalin levels were significantly high in patients with
      normoalbuminuria, were elevated in line with increased albuminuria, and showed a
      better association with estimated glomerular filtration rate (eGFR) (<60
      mL/min/1.73 m(2)) than did urinary albumin. In contrast, urinary A-megalin levels
      were increased in patients with normo- and microalbuminuria but not in those with
      macroalbuminuria. Urinary C-megalin levels were also positively associated with
      plasma inorganic phosphate and negatively with hemoglobin levels in those showing
      no features of bleeding and not taking vitamin D analogs, phosphate binders, or
      erythropoiesis-stimulating agents. CONCLUSIONS: Urinary full-length megalin
      excretion as measured by the C-megalin assay is well associated with reduced eGFR
      and linked to the severity of DN, phosphate dysregulation, and anemia, whereas
      urinary excretion of megalin ectodomain as measured by the A-megalin assay may be
      associated with distinctive mechanisms of earlier DN in type 2 diabetes.

PMID- 22410819
TI  - Retraction note: Outcomes of length-stable fixation of femoral neck fractures.

PMID- 22410818
TI  - Magnetic exchange coupling in bis-nitroxides: a theoretical analysis of the
      solvent effects.
AB  - Magnetic properties of nitroxide radicals can be greatly affected by solvent
      effects. In this study, the change of the magnetic exchange interaction J,
      coupling the two unpaired electrons of a model solvated antiferromagnetic bis
      iminyl-nitroxide molecule (2IN), is rationalized thanks to different geometric
      and electronic criteria provided by density functional theory calculations. It is
      shown that for a given geometry, simple tools can be used to analyze with good
      accuracy the dependence of J with the solvent polarity. Estimates of two
      important magnetic parameters are given: the magnetic orbitals exchange and the
      in-site energy gap between ionic and neutral configurations. 2IN can be engaged
      in different hydrogen-bonds with first shell water molecules, modifying both the
      2IN geometry and the electrostatic potential felt by the molecule. In all, the
      additivity of electrostatic and hydrogen-bond solvent effects is found to be
      responsible for J variations as large as 50%.

PMID- 22410821
TI  - Controlled fabrication of silver nanoneedles array for SERS and their application
      in rapid detection of narcotics.
AB  - Novel surface-enhanced Raman scattering (SERS) substrates with high SERS-activity
      are ideal for novel SERS sensors, detectors to detect illicitly sold narcotics
      and explosives. The key to the wider application of SERS technique is to develop
      plasmon resonant structure with novel geometries to enhance Raman signals and to
      control the periodic ordering of these structures over a large area to obtain
      reproducible Raman enhancement. In this work, a simple Ar(+)-ion sputtering route
      has been developed to fabricate silver nanoneedles arrays on silicon substrates
      for SERS-active substrates to detect trace-level illicitly sold narcotics. These
      silver nanoneedles possess a very sharp apex with an apex diameter of 15 nm and
      an apex angle of 20 degrees . The SERS enhancement factor of greater than 10(10)
      was reproducibly achieved by the well-aligned nanoneedles arrays. Furthermore,
      ketamine hydrochloride molecules, one kind of illicitly sold narcotics, can be
      detected down to 27 ppb by using our SERS substrate within 3 s, indicating the
      sensitivity of our SERS substrates for trace amounts of narcotics and that SERS
      technology can become an important analytical technique in forensic laboratories
      because it can provide a rapid and nondestructive method for trace detection.

PMID- 22410820
TI  - The effect of gemcitabine/paclitaxel chemotherapy on the survival of patients
      with metastatic urothelial cancers.
AB  - BACKGROUND: To evaluate the survival benefit of gemcitabine and paclitaxel (GT)
      chemotherapy for patients with metastatic urothelial cancer (UC), a retrospective
      analysis was performed to compare the overall survival in two periods: before
      (group I) and after (group II) the introduction of GT chemotherapy. PATIENTS AND
      METHODS: Eighty-five patients with metastatic UC were treated with MEC/MVAC
      (methotrexate, epirubicin, and cisplatin / methotrexate, vinblastine,
      doxorubicin, and cisplatin) or GT between 1995 and 2007. The response rate,
      maintenance rate, maintenance duration of each regimen, and the survival times of
      responding patients in each group were evaluated retrospectively. RESULTS: The
      median survival of patients in group IotaI (20 months) was significantly longer
      than that for group I (13 months) (p = 0.03). Especially in patients with a
      favorable response (CR/PR) to induction chemotherapy, the median survival period
      was significantly different between group Iota and group II (median 15 and 28
      months, respectively; p = 0.02). The rate of the shift to maintenance
      chemotherapy when using GT chemotherapy was significantly higher than with
      MEC/MVAC chemotherapy alone (p < 0.05), and the cessation rate due to adverse
      effects was significantly lower when using GT chemotherapy (26.1%) than MEC/MVAC
      in group Iota (42.1%). CONCLUSION: Our results demonstrated that the
      administration of GT chemotherapy may be useful to improve the survival of
      patients with metastatic UC. This effect was significant, especially among those
      who were sensitive to the induction course of first-line chemotherapy. The
      excellent tolerability of GT regimens mean that they may be suitable for
      maintenance chemotherapy.

PMID- 22410822
TI  - Cool seasons are related to poor prognosis in patients with infective
      endocarditis.
AB  - Many cardiac diseases demonstrate seasonal variations in the incidence and
      mortality. This study was designed to investigate whether the mortality of
      infective endocarditis (IE) was higher in cool seasons and to evaluate the
      effects of cool climate for IE. We enrolled 100 IE patients with vegetations in
      our hospital. The temperatures of the IE episodes were defined as the monthly
      average temperatures of the admission days. The average temperatures in the cool
      (fall/winter) and warm seasons (spring/summer) were 19.2 degrees C and 27.6
      degrees C, respectively. In addition, patients admitted with the diagnosis of IE
      were identified from the National Health Insurance Research Database (NHIRD) and
      the in-hospital mortality rates in cool and warm seasons were compared to
      validate the findings derived from the data of our hospital. The mortality rate
      for IE was significantly higher in fall/winter than in spring/summer which
      presents consistently in the patient population of our hospital (32.7% versus
      12.5%, p = 0.017) and from NHIRD (10.4% versus 4.6%, p = 0.019). IE episodes
      which occurred during cool seasons presented with a higher rate of heart failure
      (44.2% versus 22.9%, p = 0.025) and D-dimer level (5.5 +/- 3.8 versus 2.4 +/- 1.8
      MUg/ml, p = 0.017) at admission than that of warm seasons. These results may
      reflect the impact of temperatures during the pre-hospitalized period on the
      disease process. In the multivariate analysis, Staphylococcal infection, left
      ventricular hypertrophy, left ventricular systolic dysfunction and temperature
      were the independent predictors of mortalities in IE patients.

PMID- 22410823
TI  - Atmospheric conditions during high ragweed pollen concentrations in Zagreb,
      Croatia.
AB  - We examined the atmospheric conditions favourable to the occurrence of maximum
      concentrations of ragweed pollen with an extremely high risk of producing
      allergy. Over the 2002-2009 period, daily pollen data collected in Zagreb were
      used to identify two periods of high pollen concentration (> 600 grains/m(3)) for
      our analysis: period A (3-4 September 2002) and period B (6-7 September 2003).
      Synoptic conditions in both periods were very similar: Croatia was under the
      influence of a lower sector high pressure system moving slowly eastward over
      Eastern Europe. During the 2002-2009 period, this type of weather pattern (on ~
      70% of days), in conjunction with almost non-gradient surface pressure conditions
      in the area (on ~ 30% of days) characterised days when the daily pollen
      concentrations were higher than 400 grains/m(3). Numerical experiments using a
      mesoscale model at fine resolution showed successful multi-day simulations
      reproducing the local topographic influence on wind flow and in reasonable
      agreement with available observations. According to the model, the relatively
      weak synoptic flow (predominantly from the eastern direction) allowed local
      thermal circulations to develop over Zagreb during both high pollen episodes. Two
      hour pollen concentrations and 48-h back-trajectories indicated that regional
      range transport of pollen grains from the central Pannonian Plain was the cause
      of the high pollen concentrations during period A. During period B, the north
      westward regional-range transport in Zagreb was supplemented significantly by
      pronounced horizontal recirculation of pollen grains. This recirculation happened
      within the diurnal local circulation over the city, causing a late-evening
      increase in pollen concentration.

PMID- 22410824
TI  - A numerical model of birch pollen emission and dispersion in the atmosphere.
      Description of the emission module.
AB  - A birch pollen emission model is described and its main features are discussed.
      The development of the model is based on a double-threshold temperature sum model
      that describes the propagation of the flowering season and naturally links to the
      thermal time models to predict the onset and duration of flowering. For the
      flowering season, the emission model considers ambient humidity and precipitation
      rate, both of which suppress the pollen release, as well as wind speed and
      turbulence intensity, which promote it. These dependencies are qualitatively
      evaluated using the aerobiological observations. Reflecting the probabilistic
      character of the flowering of an individual tree in a population, the model
      introduces relaxation functions at the start and end of the season. The physical
      basis of the suggested birch pollen emission model is compared with another
      comprehensive emission module reported in literature. The emission model has been
      implemented in the SILAM dispersion modelling system, the results of which are
      evaluated in a companion paper.

PMID- 22410825
TI  - Thermographic evaluation of climatic conditions on lambs from different genetic
      groups.
AB  - In production systems the characterization of genetic resources in relation to
      their capacity to respond to environmental conditions is necessary. The objective
      of this study was to evaluate the use of infrared thermography for separation of
      animals from different genetic groups and determine which phenotypic traits are
      important for climatic adaptation. A total of 126 suckling lambs from four
      different genetic groups (Santa Ines--SI, Bergamasca--B, Bergamasca X Santa Ines-
      BS, and Ile de France X Santa Ines--IL) were used. The animals were divided into
      two groups, one housed and another in an outside paddock. Thermograph photographs
      were taken at four-hour intervals over three full days. Temperatures of the nose,
      skull, neck, fore and rear flanks and rump were measured, as well as coat depth,
      the density and length of hairs, reflectance and color. The daily temperature
      range during the experimental period was more than 20 degrees C, with animals
      experiencing heat (12 h to 15 h) and cold (24 h to 4 h) stress. The three main
      phenotypic traits that influenced genetic group separation were hair density,
      height of coat, and length of hairs. Thermograph temperatures were able to detect
      different responses of the genetic groups to the environment. Therefore, infrared
      thermography is a promising technique to evaluate the response of animals to the
      environment and to differentiate between genetic groups.

PMID- 22410826
TI  - Association of monthly frequencies of diverse diseases in the calls to the public
      emergency service of the city of Buenos Aires during 1999-2004 with
      meteorological variables and seasons.
AB  - This work aims to study associations between monthly averages of meteorological
      variables and monthly frequencies of diverse diseases in the calls to the public
      ambulance emergency service of the city of Buenos Aires during the years 1999
      2004. Throughout this time period no changes were made in the classification
      codes of the illnesses. Heart disease, arrhythmia, heart failure, cardiopulmonary
      arrest, angina pectoris, psychiatric diseases, stroke, transient ischemic attack,
      syncope and the total number of calls were analyzed against 11 weather variables
      and the four seasons. All illnesses exhibited some seasonal behavior, except
      cardiorespiratory arrest and angina pectoris. The largest frequencies of
      illnesses that exhibited some association with the meteorological variables used
      to occur in winter, except the psychiatric cases. Heart failure, stroke,
      psychiatric diseases and the total number of calls showed significant
      correlations with the 11 meteorological variables considered, and the largest
      indices (absolute values above 0.6) were found for the former two pathologies. On
      the other side, cardiorespiratory arrest and angina pectoris revealed no
      significant correlations and nearly null indices. Variables associated with
      temperature were the meteorological proxies with the largest correlations against
      diseases. Pressure and humidity mostly exhibited positive correlations, which is
      the opposite of variables related to temperature. Contrary to all other diseases,
      psychiatric pathologies showed a clear predominance of positive correlations.
      Finally, the association degree of the medical dataset with recurrent patterns
      was further evaluated through Fourier analysis, to assess the presence of
      statistically significant behavior. In the Northern Hemisphere high morbidity and
      mortality rates in December are usually assigned to diverse factors in relation
      to the holidays, but such an effect is not observed in the present analysis.
      There seems to be no clearly preferred meteorological proxy among the different
      types of temperatures used. It is shown that the amount of occurrences depends
      mainly on season rather on its strength quantified by temperature.

PMID- 22410827
TI  - A 13 kg intra-abdominal mass: a case of mesenteric fibromatosis.
AB  - Mesenteric fibromatosis is a benign fibrous tumor, characterized by
      proliferations of fibroblasts and myofibroblasts, locally aggressive but non
      metastasizing. It can occur rarely in association with familial adenomatous
      polyposis or sporadically (related with previous trauma, abdominal surgery or
      prolonged estrogens intake). Small bowel mesentery is the most common site of
      origin of mesenteric fibromatosis. The authors report a case of a 47-years-old
      male with a large mass involving the mesentery of the first jejunal loops. The
      patient was symptomatic for nausea and referred an increasing abdominal
      circumference; a CT scan showed a huge mass (34 * 29 * 15 cm) very close to the
      superior mesenteric vessel roots. The surgical treatment consisted in the en bloc
      removal of the mass weighting 13 kg.

PMID- 22410828
TI  - Endoplasmic reticulum stress in skeletal muscle homeostasis and disease.
AB  - Our appreciation of the role of endoplasmic reticulum (ER) stress pathways in
      both skeletal muscle homeostasis and the progression of muscle diseases is
      gaining momentum. This review provides insight into ER stress mechanisms during
      physiologic and pathological disturbances in skeletal muscle. The role of ER
      stress in the response to dietary alterations and acute stressors, including its
      role in autoimmune and genetic muscle disorders, has been described. Recent
      studies identifying ER stress markers in diseased skeletal muscle are noted. The
      emerging evidence for ER-mitochondrial interplay in skeletal muscle and its
      importance during chronic ER stress in activation of both inflammatory and cell
      death pathways (autophagy, necrosis, and apoptosis) have been discussed. Thus,
      understanding the ER stress-related molecular pathways underlying physiologic and
      pathological phenotypes in healthy and diseased skeletal muscle should lead to
      novel therapeutic targets for muscle disease.

PMID- 22410829
TI  - Morbidity and mortality in adult polymyositis and dermatomyositis.
AB  - Before the use of corticosteroids, the prognosis for polymyositis/dermatomyositis
      (PM/DM) was extremely poor. To date, although overall prognosis appears to be
      better, PM and DM are still considered to be associated with increased morbidity,
      primarily related to severe muscle weakness and visceral involvement. Recent
      series underline that only 20% to 40% of treated patients will achieve PM/DM
      remission, whereas 60% to 80% will experience a polycyclic or chronic, continuous
      course of the disease. PM/DM further continues to have a great impact on life in
      medium- and long-term follow-up, as up to 80% of treated patients are still
      disabled (using Health Assessment Questionnaire scores). The overall mortality
      ratio in PM/DM patients also remains threefold higher compared with the general
      population, with cancer, lung, and cardiac complications and infections being the
      most common causes of deaths. Predictive factors for a poor prognosis in PM/DM
      patients are older age, involvement of lung and cardiac systems, dysphagia,
      cancer, and serum myositis-specific antibodies (including coexistent presence of
      anti-Ro52 and anti-Jo1 antibodies, anti-signal recognition particle antibody,
      anti-155/140, and anti-CADM-140 antibodies).

PMID- 22410831
TI  - The biology of happiness. Chasing pleasure and human destiny.

PMID- 22410830
TI  - Transcription goes digital.
AB  - Transcription is a complex process that integrates the state of the cell and its
      environment to generate adequate responses for cell fitness and survival. Recent
      microscopy experiments have been able to monitor transcription from single genes
      in individual cells. These observations have revealed two striking features:
      transcriptional activity can vary markedly from one cell to another, and is
      subject to large changes over time, sometimes within minutes. How the chromatin
      structure, transcription machinery assembly and signalling networks generate such
      patterns is still unclear. In this review, we present the techniques used to
      investigate transcription from single genes, introduce quantitative modelling
      tools, and discuss transcription mechanisms and their implications for gene
      expression regulation.

PMID- 22410832
TI  - English of science or scientific English?

PMID- 22410833
TI  - Clinical outcome of rectal cancer in patients >= 80 years treated in southern
      France (PACA region) between 2002 and 2005.
AB  - BACKGROUND: Rectal cancer in patients aged >= 80 years is increasingly more
      frequent. Little is known regarding their clinical history and outcome after
      treatment. This retrospective study was undertaken to provide data on this
      situation. MATERIAL AND METHOD: A questionnaire was sent to the medical doctors
      of 414 patients listed in the database of Regime General of Securite Sociale,
      living in the Provence-Alpes-Cote d'Azur (PACA) region between 2002 and 2005,
      aged >= 80 years, and registered as having rectal cancer. Survival was analyzed
      and correlated with patients' and treatment characteristics. RESULTS: Validated
      questionnaire was available for 78 patients representing close to 20% of the PACA
      targeted population. The majority of patients presented a T3 tumor treated with
      surgery (61 cases). Median follow-up for the 78 patients was 42 months and the 5
      year overall survival was 51%. In the multivariate analysis, the main prognostic
      factors were gender (better survival in women), age <= 85 years, and most of all
      performance of surgery. CONCLUSION: Rectal cancer for patients between 79 and 85
      years does not differ much from that in younger patients and can be treated in a
      similar manner--depending on the patient's general condition. In patients > 85
      years, it is advisable to reduce surgical trauma as much as possible.

PMID- 22410834
TI  - Prognostic factors for local control and survival in patients with spinal cord
      compression from myeloma.
AB  - BACKGROUND: This retrospective study aimed to identify prognostic factors for
      local control and survival in 214 patients irradiated for spinal cord compression
      (SCC) from myeloma. PATIENTS AND METHODS: Ten potential prognostic factors were
      investigated including age, gender, Eastern Cooperative Oncology Group
      performance score (ECOG-PS), number of involved vertebrae, ambulatory status,
      other osseous lesions, extraosseous lesions, interval from first diagnosis of
      myeloma to SCC, time developing motor deficits before radiotherapy (RT), and the
      RT schedule (short-course vs. long-course RT). RESULTS: On univariate analysis,
      no factor was associated with local control of SCC. Survival was associated with
      ECOG-PS (p < 0.001), ambulatory status (p < 0.001), other osseous lesions (p <
      0.001), and extraosseous lesions (p < 0.001). On multivariate analysis, these
      prognostic factors maintained significance. CONCLUSION: New independent
      prognostic factors were identified for survival after RT of SCC from myeloma.
      These factors can help tailor treatment to the individual patient.

PMID- 22410835
TI  - Meningioma as second malignant neoplasm after oncological treatment during
      childhood.
AB  - A total of 38 patients (18 female/20 male) with childhood meningioma were
      recruited from the German registry HIT-Endo (1989-2009). In 5 cases meningioma
      occurred as second malignant neoplasm (SMN). Histologies were confirmed by
      reference assessment in all cases (SMN: 2 WHO I, 1 WHO II, 2 WHO III). The SMNs
      were diagnosed at a median age of 12.4 years with a median latency of 10.2 years
      after primary malignancy (PMN; 4 brain tumors, 1 lymphoblastic leukemia; median
      age at diagnosis 2.7 years). Meningioma occurred as SMN in the irradiated field
      of PMN (range 12-54 Gy). The outcome after treatment of SMN meningioma
      (surgery/irradiation) was favorable in terms of psychosocial status and
      functional capacity in 4 of 5 patients (1 death). We conclude that survivors of
      childhood cancer who were exposed to radiation therapy at young age harbor the
      risk of developing meningioma as a SMN at a particularly short latency period in
      case of high dose exposure.

PMID- 22410836
TI  - Postoperative periclavicular radiotherapy in breast cancer patients with 1-3
      positive axillary lymph nodes. Outcome and morbidity.
AB  - PURPOSE: The goal of this work was to examine the possible influence of
      periclavicular irradiation on outcome of breast cancer patients with 1-3 positive
      lymph nodes with special emphasis on late toxicity rates. PATIENTS AND METHODS:
      Between 1997 and 2000, 235 breast cancer patients (T1-2, 1-3 involved lymph
      nodes) were treated at our department following breast conservative surgery: 139
      patients (59.1%) had one, 62 patients (26.4%) two, and 34 patients (14.5%) three
      positive lymph nodes. Extracapsular spread (ECS) was described in 72 patients
      (30.6%). There were 67 patients (28.5%) who received additional radiotherapy to
      the ipsilateral periclavicular lymph nodes (PCLNI), while 168 patients did not
      (noPCLNI). Patients were re-examined or contacted by phone with regard to
      treatment-related late effects. RESULTS: After a median follow-up of 78 months
      (range 7-107 months), 22 patients (9.4%) developed local, 9 (3.8%) axillary, 4
      periclavicular (1.7%), and 41 distant failure (17.4%). The actuarial 8-year
      locoregional recurrence-free (LRRFS), disease-free (DFS), and overall survival
      rates (OS) were 83%, 67%, and 74%, respectively. Survival data for the PCLNI vs.
      noPCLNI group were 72% vs. 89% (p = 0.3), 56% vs. 73% (p = 0.4), and 86% vs. 70%
      (p = 0.3), respectively. No higher toxicity rates were reported in the PCLNI
      group compared to the noPCLNI group. CONCLUSION: We could not demonstrate any
      difference in outcome in breast cancer patients with 1-3 positive axillary lymph
      node metastases with or without periclavicular lymph node irradiation. In
      addition, patients with PCLNI did not complain about higher rates of late
      toxicities. However, patients with ECS, which may predict for locoregional
      failure, may benefit from adjuvant periclavicular irradiation.

PMID- 22410837
TI  - [What is the influence of local treatment on overall survival in early prostate
      cancer?].

PMID- 22410838
TI  - [Neoadjuvant radiochemotherapy with 5-FU plus oxaliplatin for locally advanced
      rectal cancer. First results from phase III trials].

PMID- 22410839
TI  - PET and MRI for the evaluation of regional myocardial perfusion and wall
      thickening after myocardial infarction.
AB  - BACKGROUND: Deterioration of left ventricular (LV) function after myocardial
      infarction (MI) is a major cause of heart failure. Myocardial perfusion
      performance may play an important role in deterioration or improvement in LV
      function after MI. The aim of this study was to evaluate the myocardial perfusion
      reserve (MPR) and stress perfusion in deteriorating and non-deteriorating LV
      segments in patients after MI by PET and MRI, respectively. METHODS: Regional
      wall thickening of 352 segments in 22 patients was assessed at 4 and 24 months
      after MI by cardiac MRI. PET was performed to evaluate MPR and adenosine stress
      (13)N-ammonia perfusion 24 months after MI. Segments were divided into four
      groups according to deterioration or improvement in wall thickening. RESULTS:
      Normal functional segments at 4 months after MI that remained stable had a
      significantly higher mean MPR and mean stress perfusion PET value than
      deteriorated segments (p < 0.001). Furthermore, dysfunctional segments that
      improved had a significantly higher mean stress perfusion PET value than
      dysfunctional segments that remained dysfunctional (p < 0.001). CONCLUSION: This
      study demonstrated the additional value of myocardial perfusion assessment in
      relation to the functional integrity of the injured myocardium. Segmental
      functional LV improvement after MI was associated with better regional myocardial
      perfusion characteristics. Furthermore, the amount of wall thickening reduction
      was associated with regional myocardial perfusion abnormalities in patients after
      MI.

PMID- 22410841
TI  - Malignant masquerade of xanthogranulomatous cholecystitis on intraoperative
      ultrasound of the liver.

PMID- 22410840
TI  - In vitro exposure to fullerene C(60)  influences redox state and lipid
      peroxidation in brain and gills from Cyprinus carpio (Cyprinidae).
AB  - Studies concerning the impact of nanomaterials, especially fullerene (C(60) ), in
      fresh water environments and their effects on the physiology of aquatic organisms
      are still scarce and conflicting. We aimed to assess in vitro effects of
      fullerene in brain and gill homogenates of carp Cyprinus carpio, evaluating redox
      parameters. A fullerene suspension was prepared by continued stirring under
      fluorescent light during two months. The suspension concentration was measured by
      total carbon content and ultraviolet-visible spectroscopy nephelometry.
      Characterization of C(60) aggregates was performed with an enhanced dark-field
      microscopy system and transmission electronic microscopy. Organ homogenates were
      exposed during 1, 2, and 4 h under fluorescent light. Redox parameters evaluated
      were reduced glutathione and oxidized glutathione, cysteine and cystine, total
      antioxidant capacity; activity of the antioxidant enzymes glutathione S
      transferase and glutathione reductase (GR), and lipid peroxidation (TBARS assay).
      Fullerene induced a significant increase (p < 0.05) in lipid peroxidation after 2
      h in both organs and reduced GR activity after 1 h (gills) and 4 h (brain) and
      antioxidant capacity after 4 h (brain). Levels of oxidized glutathione increased
      in the brain at 1 h and decreased at 2 h as well. Given these results, it can be
      concluded that C(60) can induce redox disruption via thiol/disulfide pathway,
      leading to oxidative damage (higher TBARS values) and loss of antioxidant
      competence.

PMID- 22410842
TI  - Thermopower and conductance for a graphene p-n junction.
AB  - The  thermopower and conductance in a zigzag graphene p-n junction are studied by
      using the nonequilibrium Green's function method combined with the tight-binding
      Hamiltonian. Our results show that the conductance and thermopower of the
      junction can be modulated by its width, the potential drop, and the applied
      perpendicular magnetic fields. A narrow graphene p-n junction shows insulating
      characteristics, and its thermopower is much larger than that of the wider one
      around the Dirac point. The insulating characteristic of the junction decreases
      as the width increases. In particular, with increasing junction width or the
      potential drop, the first conductance plateau is strongly enhanced and the
      thermopower is inverted around the Dirac point. A perpendicular magnetic field
      strongly suppresses the conductance and enhances the thermopower in the p-n
      region. The influence of edge vacancy defects on the conductance and thermopower
      is also discussed. Our results provide theoretical references for modulating the
      electronic and thermal properties of a graphene p-n junction by tuning its
      geometry and working conditions.

PMID- 22410843
TI  - Handedness in nature: first evidence on manual laterality on bimanual coordinated
      tube task in wild primates.
AB  - Handedness is a defining feature of human manual skill and understanding the
      origin of manual specialization remains a central topic of inquiry in
      anthropology and other sciences. In this study, we examined hand preference in a
      sample of wild primates on a task that requires bimanual coordinated actions
      (tube task) that has been widely used in captive primates. The Sichuan snub-nosed
      monkey (Rhinopithecus roxellana) is an arboreal Old World monkey species that is
      endemic to China, and 24 adult individuals from the Qinling Mountains of China
      were included for the analysis of hand preference in the tube task. All subjects
      showed strong individual hand preferences and significant group-level left
      handedness was found. There were no significant differences between males and
      females for either direction or strength of hand preference. Strength of hand
      preferences of adults was significantly greater than juveniles. Use of the index
      finger to extract the food was the dominant extractive-act. Our findings
      represent the first evidence of population-level left-handedness in wild Old
      World monkeys and broaden our knowledge on evaluating primate hand preference via
      experimental manipulation in natural conditions.

PMID- 22410844
TI  - Socioeconomic and behavioral risk factors for mortality: do risk factors observed
      after spinal cord injury parallel those from the general USA population?
AB  - OBJECTIVE: To evaluate the association of demographic, behavioral and
      socioeconomic factors with all-cause mortality while controlling for health
      status among a cohort of participants with severe disability related to spinal
      cord injury (SCI). STUDY DESIGN: Prospective cohort study. SETTING: Data were
      analyzed at a major medical university in the Southeast United States of America.
      METHODS: Participants included 1361 adults with traumatic SCI of at least 1-year
      duration who were recruited through a large specialty hospital in the Southeast
      United States of America. Three Cox proportional hazard models were generated
      relating the predictors to all-cause mortality. RESULTS: Age, disability, smoking
      and income were significant in the final model. Both current (hazard ratio
      (HR)=2.03, 95% confidence interval (CI)=1.46-2.82) and former smokers (HR=1.58,
      CI=1.16-2.16) were at elevated hazard of mortality, as were those with incomes
      below $10,000 (HR=2.29, CI=1.53-3.44) and between $10,000 and $35,000 (HR=1.47,
      CI=1.03-2.10). CONCLUSIONS: Even after controlling for health and severity of
      disability, the coefficients for smoking and income were significant, exceeding
      that reported previously within the general population. The importance of these
      factors may be magnified after severe disability, even though life expectancy is
      already greatly diminished in this population.

PMID- 22410846
TI  - Contrasting effects of cord injury on intravenous and oral pharmacokinetics of
      diclofenac: a drug with intermediate hepatic extraction.
AB  - STUDY DESIGN: Laboratory investigation in rats submitted to experimental spinal
      cord injury (SCI). OBJECTIVE: To determine the effect of acute SCI on the
      pharmacokinetics of diclofenac, a marker drug of intermediate hepatic extraction,
      administered by the intravenous and the oral routes. METHODS: Female Wistar rats
      were submitted to complete section of the spinal cord at the T8 level. SCI and
      sham-injured rats received 3.2 mg kg(-1) of diclofenac sodium either
      intravenously or orally, diclofenac concentration was measured in whole blood
      samples and pharmacokinetic parameters were estimated. Diclofenac was not
      selected as test drug because of its therapeutic properties, but because to its
      biopharmaceutical properties, that is, intermediate hepatic extraction. RESULTS:
      Diclofenac bioavailability after intravenous administration was increased in
      injured rats compared with controls due to a reduced clearance. In contrast, oral
      diclofenac bioavailability was diminished in SCI animals due to a reduction in
      drug absorption, which overrides the effect on clearance. CONCLUSION: Acute SCI
      induces significant pharmacokinetic changes for diclofenac, a marker drug with
      intermediate hepatic extraction. SCI-induced pharmacokinetic changes are not only
      determined by injury characteristics, but also by the route of administration and
      the biopharmaceutical properties of the studied drug.

PMID- 22410845
TI  - On the feasibility of using motor imagery EEG-based brain-computer interface in
      chronic tetraplegics for assistive robotic arm control: a clinical test and long
      term post-trial follow-up.
AB  - STUDY DESIGN: Survey and long-term clinical post-trial follow-up
      (interviews/correspondence) on nine chronic, post spinal cord injury (SCI)
      tetraplegics. OBJECTIVE: To assess feasibility of the use of
      Electroencephalography-based Brain-Computer Interface (EEG-BCI) for
      reaching/grasping assistance in tetraplegics, through a robotic arm. SETTINGS:
      Physical and (neuromuscular) Rehabilitation Medicine, Cardiology, Neurosurgery
      Clinic Divisions of TEHBA and UMPCD, in collaboration with 'Brain2Robot'
      (composed of the European Commission-funded Marie Curie Excellence Team by the
      same name, hosted by Fraunhofer Institute-FIRST), in the second part of 2008.
      METHODS: Enrolled patients underwent EEG-BCI preliminary training and robot
      control sessions. Statistics entailed multiple linear regressions and cluster
      analysis. A follow-up-custom questionnaire based-including patients' perception
      of their EEG-BCI control capacity was continued up to 14 months after initial
      experiments. RESULTS: EEG-BCI performance/calibration-phase classification
      accuracy averaged 81.0%; feedback training sessions averaged 70.5% accuracy for 7
      subjects who completed at least one feedback training session; 7 (77.7%) of 9
      subjects reported having felt control of the cursor; and 3 (33.3%) subjects felt
      that they were also controlling the robot through their movement imagination. No
      significant side effects occurred. BCI performance was positively correlated with
      beta (13-30 Hz) EEG spectral power density (coefficient 0.432, standardized
      coefficient 0.745, P-value=0.025); another possible influence was sensory AIS
      score (range: 0 min to 224 max, coefficient -0.177, standardized coefficient 
      0.512, P=0.089). CONCLUSION: Limited but real potential for self-assistance in
      chronic tetraplegics by EEG-BCI-actuated mechatronic devices was found, which was
      mainly related to spectral density in the beta range positively (increasing
      therewith) and to AIS sensory score negatively.

PMID- 22410847
TI  - Biopsychosocial outcomes in individuals with and without spinal cord injury: a
      Swiss comparative study.
AB  - STUDY DESIGN: Multicentre controlled study. OBJECTIVES: To investigate if
      individuals with and without spinal cord injury (SCI) differ in biopsychosocial
      variables according to the International Classification of Functioning,
      Disability and Health (ICF). SETTING: Participants were recruited through three
      major SCI rehabilitation centres in Switzerland. METHODS: A convenience sample of
      people with SCI (N=102) and a matched non-SCI sample (N=73) were compared
      according to secondary conditions, pain, depressive symptoms, participation,
      social support, self-efficacy, self-esteem, coping and sense of coherence.
      Difference tests and multivariate logistic regression analyses to predict the
      likelihood of group membership were calculated. RESULTS: People with SCI reported
      more health conditions, higher levels of anxiety and depressive symptoms, worse
      pain and pain interference, lower level of participation and social support,
      lower self-efficacy, self-esteem and task- and emotion-oriented coping. The two
      samples did not differ in satisfaction with social support, in use of avoidance
      oriented coping and in sense of coherence. Health conditions, pain interference,
      participation and age were found to be significant predictors of the likelihood
      of group membership. In the logistic regression models, the number of health
      conditions, limitations due to health conditions, pain interference,
      participation, task-oriented coping and age are significant predictors of group
      membership, accounting for 55% of variation. CONCLUSION: Health conditions, pain
      interference and participation seemed to be the areas of biopsychosocial
      functioning that are substantially influenced by SCI. Potential buffering
      resources seem to be diminished in individuals with SCI. In rehabilitation
      practice, prevention of secondary conditions, treatment of pain, enhancement of
      participation and strengthening resources should be addressed.

PMID- 22410848
TI  - Return to work and productive activities following a spinal cord injury: the role
      of income and insurance.
AB  - STUDY DESIGN: We analyzed longitudinal data on secondary outcomes from
      participants in a telerehabilitation study. OBJECTIVES: To examine the factors
      affecting return to productive activities and employment and the time to these
      events following a spinal cord injury (SCI). SETTING: A large southeastern
      rehabilitation hospital in the United States. METHODS: We used hazard regression
      models to analyze data from newly injured people (n=111) participating in an
      educational intervention post discharge who were followed for up to 2 years.
      Outcomes were time to return to productive activities and employment. RESULTS:
      Increasing age and being on Medicaid significantly decreased the likelihood of
      returning to productive activities (P<0.01), while being white (P<0.05) and
      having a higher median income (P<0.001) significantly increased this probability.
      The same factors, bar being on Medicaid, affected the return to employment.
      Whites returned to productive activities 2.5 times sooner than African Americans
      and employment twice as fast (P<0.001). Being in the 75th income percentile
      compared with the 25th shortened time to employment by 209 days. CONCLUSION:
      Findings here suggest that income and race affect the time to return to
      productivity and employment, while being on Medicaid also has a role in general
      post injury productivity.

PMID- 22410849
TI  - Acquired neurosyphilis presenting as movement disorders.
AB  - After a significant decline in the second half of the 20th century, rates of
      infection with syphilis are again on the rise. Long known as the "great
      mimicker," syphilitic infection can be difficult to recognize clinically and this
      particularly holds true for neurologic manifestations of the disease. Gait
      dysfunction and sensory ataxia have been historically well described in
      neurosyphilis literature; however, other movement disorders have been reported to
      a lesser extent. Here we review reports of movement disorders in acquired
      neurosyphilis. Given its increasing incidence, it is important to be cognizant of
      its diverse presentation and retain a high index of suspicion for syphilis,
      particularly as it is completely curable in the early stages.

PMID- 22410850
TI  - Portal vein thrombosis after EUS-guided pancreatic cyst ablation.

PMID- 22410852
TI  - Osteopontin biomarker in inflammatory bowel disease, animal models and target for
      drug discovery.

PMID- 22410851
TI  - Epstein-Barr virus infection is common in inflamed gastrointestinal mucosa.
AB  - BACKGROUND AND AIMS: Epstein-Barr virus (EBV) is present in the malignant
      epithelial cells of 10% of all gastric adenocarcinomas; however, localization of
      the virus in normal gastrointestinal mucosa is largely unexplored. In the present
      study, we measured EBV DNA and localized viral gene products in gastritis
      specimens (n = 89), normal gastric and colonic mucosa (n = 14), Crohn's disease
      (n = 9), and ulcerative colitis (n = 11) tissues. METHODS: A battery of sensitive
      and specific quantitative polymerase chain reactions targeted six disparate
      regions of the EBV genome: BamH1 W, EBNA1, LMP1, LMP2, BZLF1, and EBER1. EBV
      infection was localized by EBV-encoded RNA (EBER) in situ hybridization and by
      immunohistochemical stains for viral latent proteins LMP1 and LMP2 and for viral
      lytic proteins BMRF1 and BZLF1. B lymphocytes were identified using CD20
      immunostains. RESULTS: EBV DNA was essentially undetectable in normal gastric
      mucosa but was present in 46% of gastritis lesions, 44% of normal colonic mucosa,
      55% of Crohn's disease, and 64% of ulcerative colitis samples. Levels of EBV DNA
      exceeded what would be expected based on the numbers of B lymphocytes in inflamed
      tissues, suggesting that EBV is preferentially localized to inflammatory
      gastrointestinal lesions. Histochemical staining revealed EBER expression in
      lymphoid cells of some PCR-positive lesions. The viral lytic viral proteins,
      BMRF1 and BZLF1, were expressed in lymphoid cells of two ulcerative colitis
      tissues, both of which had relatively high viral loads by quantitative PCR.
      CONCLUSION: EBV-infected lymphocytes are frequently present in inflamed gastric
      and colonic mucosa. Active viral replication in some lesions raises the
      possibility of virus-related perpetuation of gastrointestinal inflammation.

PMID- 22410853
TI  - Inhibitory morphogens and monopodial branching of the embryonic chicken lung.
AB  - BACKGROUND: Branching morphogenesis generates a diverse array of epithelial
      patterns, including dichotomous and monopodial geometries. Dichotomous branching
      can be instructed by concentration gradients of epithelial-derived inhibitory
      morphogens, including transforming growth factor-beta (TGFbeta), which is
      responsible for ramification of the pubertal mammary gland. Here, we investigated
      the role of autocrine inhibitory morphogens in monopodial branching morphogenesis
      of the embryonic chicken lung. RESULTS: Computational modeling and experiments
      using cultured organ explants each separately revealed that monopodial branching
      patterns cannot be specified by a single epithelial-derived autocrine morphogen
      gradient. Instead, signaling by means of TGFbeta1 and bone morphogenetic protein
      4 (BMP4) differentially affect the rates of branching and growth of the airways.
      Allometric analysis revealed that development of the epithelial tree obeys power
      law dynamics; TGFbeta1 and BMP4 have distinct but reversible effects on the
      scaling coefficient of the power law. CONCLUSIONS: These data suggest that
      although autocrine inhibition cannot specify monopodial branching, inhibitory
      morphogens define the dynamics of lung morphogenesis.

PMID- 22410855
TI  - Clostridium septicum aortitis in a patient with extensive atheromatous disease of
      the aorta.
AB  - A 69-year man presented with 3 days of progressively worsening abdominal pain,
      radiating to his back, with nausea and vomiting. Computed tomography scan of the
      abdomen showed evidence of aortitis, for which he eventually underwent surgery.
      The surgical specimen of the aorta grew Clostridium septicum that was treated
      with antibiotics.

PMID- 22410854
TI  - Analysis of membrane antigens on neutrophils from patients with sepsis.
AB  - The aim of the present study was to assess changes of cell membrane antigens on
      neutrophils in septic patients. Expression levels of neutrophil membrane antigens
      were measured employing a FACS calibur flow cytometer with several fluorescence
      labeled monoclonal antibodies. Expression levels of the CD14 antigen were higher
      in patients with sepsis than in healthy individuals. In particular, the
      expression levels of CD14 increased in patients complicated by septic shock.
      Expression levels of TLR-4 were higher in patients with sepsis or septic shock
      than in healthy individuals. Expression levels of CD11b and CD16 were lower in
      patients with sepsis or septic shock than in healthy individuals and were even
      lower in those complicated by septic shock. Expression levels of neutrophil
      membrane antigens in patients with sepsis markedly changed in the acute phase.
      However, these levels tended to return to those of healthy individuals in the
      convalescing phase. Analyses of the surface antigens on neutrophils strongly
      involved in biological defense or tissue injury are informative for understanding
      the pathology of sepsis and for conducting therapy targeting neutrophils in the
      future.

PMID- 22410856
TI  - Effects of lactoferricin B against keratitis-associated fungal biofilms.
AB  - Biofilms are considered as the most important developmental characteristics in
      ocular infections. Biofilm eradication is a major challenge today to overcome the
      incidence of drug resistance. This report demonstrates the in vitro ability of
      biofilm formation on contact lens by three common keratitis-associated fungal
      pathogens, namely, Aspergillus fumigatus, Fusarium solani, and Candida albicans.
      Antifungal sensitivity testing performed for both planktonic cells and biofilm
      revealed the sessile phenotype to be resistant at MIC levels for the planktonic
      cells and also at higher concentrations. A prototype lens care solution was also
      found to be partially effective in eradication of the mature biofilm from contact
      lenses. Lactoferricin B (Lacf, 64 MUg/ml), an antimicrobial peptide, exhibited
      almost no effect on the sessile phenotype. However, the combinatory effect of
      Lacf with antifungals against planktonic cells and biofilms of three fungal
      strains that were isolated from keratitis patients exhibited a reduction of
      antifungal dose more than eightfold. Furthermore, the effect of Lacf in lens care
      solution against biofilms in which those strains formed was eradicated
      successfully. These results suggest that lactoferricin B could be a promising
      candidate for clinical use in improving biofilm susceptibility to antifungals and
      also as an antibiofilm-antifungal additive in lens care solution.

PMID- 22410858
TI  - The effect of female height on reproductive success is negative in Western
      populations, but more variable in non-western populations.
AB  - OBJECTIVE: In this article we examine the association between female height and
      reproductive success in a US sample and present a review of previous studies on
      this association. We also outline possible biological explanations for our
      findings. METHODS: We used data from a long-term study of 5,326 female Wisconsin
      high school graduates to examine the association between female height and
      reproductive success. Twenty-one samples on this association were covered by our
      literature review. RESULTS: Shorter women had more children surviving to age 18
      than taller women, despite increased child mortality in shorter women. Taller
      women had a higher age at first birth and age at first marriage and reached a
      higher social status, but the negative effect of height on reproductive success
      persisted after controlling for these variables. However, while these effects
      were quite consistent in Western populations, they were not consistently present
      in non-Western populations. Our review also indicated that child mortality was
      almost universally higher among shorter women. CONCLUSIONS: We conclude that
      shorter women have a higher number of live births but that final reproductive
      success depends on the positive effect of height on child survival.

PMID- 22410859
TI  - Outcome assessment instruments in palliative and hospice care--a review of the
      literature.
AB  - BACKGROUND: As different definitions for PC have been used across the last three
      decades, a common terminology is lacking. To ensure quality of care, (a) a
      consensus on outcome criteria and indicators and (b) validated and applicable
      outcome assessment instruments are necessary. The aim of this study is to
      systematically review instrument for outcome assessment that have been used or
      proposed for research and clinical practice in palliative care. METHOD: A
      systematic literature search in electronic databases Cinahl, MEDLINE, EMBASE, and
      PsychoINFO until December 2009 was conducted to identify articles describing
      outcome assessment in palliative care. Following extraction of relevant
      publications, the outcome assessment instruments were categorized in outcome
      domains and target groups. RESULTS: The literature search resulted in 8,607 hits.
      Deduplication and exclusion of irrelevant or unavailable publications allowed for
      725 publications which were analyzed in detail. At least 528 different outcome
      assessment instruments were applied. Four target groups were identified:
      patients, family members, staff members, and the health care system. Fifteen
      patient domains were identified: quality of life, quality of care, symptoms and
      problems, performance status, psychological symptoms, decision-making and
      communication, place of death, stage of disease, mortality and survival, distress
      and wish to die, spirituality and personality, disease-specific outcomes,
      clinical features, meaning in life, and needs. The majority of instruments were
      found only in single cases and a minority of instruments were validated.
      Validated instruments were used more often. CONCLUSIONS: The wide scope of
      existing instruments makes consensus on a universal set of instruments for
      outcome assessment in palliative care improbable. A framework with a set of
      appropriate instruments could help (1) to harmonize the variety of tools used in
      research and clinical practice, (2) to allow for more comparability, and (3) to
      define gaps were tools maybe missing and should be developed.

PMID- 22410857
TI  - Microfabricated biomaterials for engineering 3D tissues.
AB  - Mimicking natural tissue structure is crucial for engineered tissues with
      intended applications ranging from regenerative medicine to biorobotics. Native
      tissues are highly organized at the microscale, thus making these natural
      characteristics an integral part of creating effective biomimetic tissue
      structures. There exists a growing appreciation that the incorporation of similar
      highly organized microscale structures in tissue engineering may yield a remedy
      for problems ranging from vascularization to cell function control/determination.
      In this review, we highlight the recent progress in the field of microscale
      tissue engineering and discuss the use of various biomaterials for generating
      engineered tissue structures with microscale features. In particular, we will
      discuss the use of microscale approaches to engineer the architecture of
      scaffolds, generate artificial vasculature, and control cellular orientation and
      differentiation. In addition, the emergence of microfabricated tissue units and
      the modular assembly to emulate hierarchical tissues will be discussed.

PMID- 22410860
TI  - Dying of hematologic patients--treatment characteristics in a German University
      Hospital.
AB  - The treatment of hematologic patients in palliative situations remains a major
      challenge as there are special clinical needs, e.g., transfusions and the high
      risk for infectious complications with subsequent use of broad anti-infective
      treatment. Furthermore, most hematologic patients have a relatively long history
      of disease and are acquainted with "their" wards; that is why most are treated on
      these hematologic and not on specialized palliative wards. The standardized
      approach to the care of hematologic patients with curative treatment intention is
      probably not fully appropriate for palliative patients. In order to evaluate the
      current situation of treatment characteristics in a German university hospital,
      we retrospectively evaluated the medical documentation of all patients who died
      on a hematologic ward between 2005 and 2008. While we found a high number of
      chemotherapeutic, anti-infective, analgesic, and sedative treatments, of
      transfusions, of treatment on the intensive care units, and of invasive nature,
      non-somatic interventions were rather scarce. Symptom control, e.g., for bleeding
      events or pain, was frequently not adequately achieved. With regard to the
      palliative situation, a holistic approach with the maintenance of patients'
      autonomy and the preference for dying at home, the treatment of hematologic
      patients in a palliative situation has to be reconsidered.

PMID- 22410861
TI  - Long-term oral effects in patients treated with radiochemotherapy for head and
      neck cancer.
AB  - PURPOSE: The purpose of this study is to assess the late oral complications and
      the role of salivary gland hypofunction in the severity of mucosal reaction in
      nonsurgical head and neck cancer patients, submitted to radiotherapy with or
      without chemotherapy. METHODS AND MATERIALS: Five hundred fifteen charts from
      patients treated between 2005 and 2009 were reviewed, and 41 patients met the
      inclusion criteria. Salivary gland function was assessed using a simplified
      grading system (GSX) and sialometry. Late effects were assessed using the Common
      Toxicity Criteria (CTC Version 2.0). RESULTS: The average follow-up was 17.1 (4
      51) months. A statistical correlation was found for whole salivary flow rates and
      the average CTC grades for the mucous membrane. Both unstimulated/stimulated
      whole salivary flow rates (<0.09 mL/min) were identified as potential risk
      factors (p < 0.05) and an independent predictor for late mucous membrane toxicity
      (>= grade 2). A significant correlation was also found between unstimulated
      salivary flow rates-GSX scores (p = 0.001) and CTC grades for salivary glands.
      Eighty-five percent of the patients were classified as suffering from salivary
      gland hypofunction, as well as 58.2 % considered dryness of the mouth the most
      debilitating complication. CONCLUSIONS: Considering the late effects assessed,
      the salivary gland hypofunction was the most significant and received the highest
      morbidity graduation (grade 2/grade 3); xerostomia was also considered the most
      debilitating complication after treatment. Data show the role of salivary gland
      hypofunction in the severity of late mucous membrane complication.

PMID- 22410863
TI  - Serum levels of antimicrobial peptides and proteins do not correlate with
      psoriasis severity and are increased after treatment with fumaric acid esters.
AB  - Overexpression of antimicrobial peptides and proteins (AMPs) such as human beta
      defensin-2 (hBD2), LL37, and psoriasin has frequently been observed in lesional
      skin of psoriasis patients. We aimed to evaluate whether circulating AMP levels
      correlate with disease severity, and change under therapy with fumaric acid
      esters (FAE). We studied psoriasis patients who underwent systemic therapy using
      oral FAE (Fumaderm((r))). An enzyme-linked immunosorbent assay for the detection
      of serum protein expression of hBD2, LL37, and psoriasin was performed at
      baseline and after 12-week therapy. After 12-week FAE treatment of 28 patients,
      the median PASI significantly (P < 0.0001) decreased from 27.1 to 12.5. In
      psoriasis patients, mean +/- SD serum hBD2, psoriasin, and LL37 levels at
      baseline were 295.6 +/- 93.5 pg/ml, 79.4 +/- 32.7 ng/ml, and 106.3 +/- 90 ng/ml,
      respectively, which were significantly increased when compared to healthy
      controls (110 +/- 53.7 pg/ml, P <= 0.0001; 3.1 +/- 0.7 ng/ml, P <= 0.0001; 3.8 +/
      0.9 ng/ml, P = 0.0004, respectively). After 12-week FAE treatment, a significant
      increase of serum hBD2 (339.7 +/- 74.3 pg/ml; P = 0.0046), psoriasin (106 +/-
      58.9 ng/ml; P = 0.0014), and LL37 (136.6 +/- 115.1 ng/ml; P = 0.0035) was
      observed. Correlation studies did not reveal significant relationships between
      serum AMP levels and PASI (r < 0.1; P > 0.05). In contrast to AMP expression in
      psoriatic skin serum, AMP levels seem not to correlate with disease severity.
      Increased serum AMP protein levels in psoriasis resolution are an unexpected
      observation that needs to be investigated more in detail in future studies.

PMID- 22410862
TI  - Change in extracellular fluid and arm volumes as a consequence of a single
      session of lymphatic massage followed by rest with or without compression.
AB  - PURPOSE: This study evaluated the acute effect of massage and compression
      components of lymphoedema treatment in women with and without arm lymphoedema
      secondary to breast cancer from a single treatment session. METHODS: Women with
      (n = 15) and without (n = 15) lymphoedema underwent a single session of lymphatic
      massage. Following the session, women were randomised to receive or not receive a
      compression sleeve. Measurements were taken prior to, during, and following the
      massage as well as 30 min after completion of the massage. Bioimpedance
      spectrometry (BIS) was used to measure changes in extracellular fluid volume of
      all limbs as well as 10-cm segments within the upper limbs; perometry was used to
      measure changes in total upper limb volume as well as 10-cm segments within the
      limb. RESULTS: There were no significant changes after massage with or without
      compression. The median (and interquartile range) BIS ratios
      (unaffected:affected) for the whole upper limb for women with lymphoedema changed
      from 1.152 (1.053 to 1.422) to 1.192 (1.045 to 1.410) after massage, while the
      control group changed from 1.024 (0.998 to 1.047) to 1.041 (0.982 to 1.07). The
      median change in both the BIS ratio and the total arm volume measured with
      perometry from prior to the massage to following 30-min rest changed <2%,
      irrespective of whether women used a compression garment and whether women
      presented with or without lymphoedema. Examination of 10-cm segments within the
      arm also revealed no significant change in BIS ratio from one segment to the
      next. CONCLUSION: Massage alone or the application of compression after a single
      session of lymphatic massage was ineffective for reducing lymphoedema.

PMID- 22410864
TI  - A decreased ratio between serum levels of the antagonistic angiopoietins 1 and 2
      indicates tumour progression of malignant melanoma.
AB  - The growth of solid tumours like malignant melanoma depends on the ability of
      neoplastic cells to induce angiogenesis to ensure sufficient supply with
      nutrients and oxygen. The process of angiogenesis is tightly controlled by
      positive and negative regulators. Since many of these factors can be measured in
      the serum of patients, their use as tumour markers has been suggested. The
      angiopoietins 1 and 2 have been demonstrated to be secreted by various tumour
      cells. By binding to the Tie-2 receptor on endothelial cells, they regulate
      angiogenesis. Whereas angiopoietin-1 maintains quiescence of vessels,
      angiopoietin-2 increases angiogenesis by destabilising vessels and sensitising
      them to the effect of growth factors of the VEGF family. Since both angiopoietins
      compete for the same Tie-2 receptor and cause opposite effects concerning
      angiogenesis, the ratio between these two ligands is crucial. Therefore, we have
      measured serum levels of both angiopoietins in the serum of 148 melanoma patients
      at different stages of disease. Whereas angiopoietin-1 levels did not change
      during disease progression, angiopoietin-2 levels were significantly higher in
      advanced stage disease. Compared to the established tumour-marker S100B,
      angiopoietin-2 levels or the ratio between both angiopoietins did not show
      increased sensitivity for the early detection of advanced stages of malignant
      melanoma. In conclusion, the ratio between both angiopoietins is significantly
      altered in late stage melanoma patients, shifting the balance to favour
      angiogenesis.

PMID- 22410865
TI  - The role of quantum-mechanical interference and quasi-classical effects in
      conjugated hydrocarbons.
AB  - The nature of the chemical bond in conjugated hydrocarbons is analyzed through
      the generalized product function energy partitioning (GPF-EP) method, which
      allows the calculation of the quantum-mechanical interference and quasi-classical
      contributions to the energy. The method is applied to investigate the differences
      between the chemical bonding in conjugated and non-conjugated hydrocarbon isomers
      and to evaluate the contribution from the energy components to the stabilization
      of the molecules. It is shown that in all cases quantum-mechanical interference
      has the effect of concentrating pi electron density between the two carbon atoms
      directly involved in the (C-C)pi bonds. For the conjugated isomers, this effect
      is accompanied by a substantial reduction of electron density in the pi space of
      the neighbouring (C-C)sigma bond. On the other hand, quasi-classical effects are
      shown to be responsible for the extra stabilization of the conjugated isomers, in
      which a decrease of the pi space kinetic reference energy seems to play an
      important role. Finally, it is shown that the polarization of p-like orbitals in
      compounds with alternating single and double bonds ultimately increases electron
      density in the pi space of the neighbouring (C-C)sigma bond. Therefore, quasi
      classical effects, rather than covalent ones, seem to be responsible for several
      properties of conjugated molecules, such as thermodynamic stability, planarity
      and (C-C)sigma bond shortening. The shortcomings of the delocalization concept
      are discussed.

PMID- 22410866
TI  - Simultaneous fluorescence light-up and selective multicolor nucleobase
      recognition based on sequence-dependent strong binding of berberine to DNA abasic
      site.
AB  - Label-free DNA nucleobase recognition by fluorescent small molecules has received
      much attention due to its simplicity in mutation identification and drug
      screening. However, sequence-dependent fluorescence light-up nucleobase
      recognition and multicolor emission with individual emission energy for
      individual nucleobases have been seldom realized. Herein, an abasic site (AP
      site) in a DNA duplex was employed as a binding field for berberine, one of
      isoquinoline alkaloids. Unlike weak binding of berberine to the fully matched
      DNAs without the AP site, strong binding of berberine to the AP site occurs and
      the berberine's fluorescence light-up behaviors are highly dependent on the
      target nucleobases opposite the AP site in which the targets thymine and cytosine
      produce dual emission bands, while the targets guanine and adenine only give a
      single emission band. Furthermore, more intense emissions are observed for the
      target pyrimidines than purines. The flanking bases of the AP site also produce
      some modifications of the berberine's emission behavior. The binding selectivity
      of berberine at the AP site is also confirmed by measurements of fluorescence
      resonance energy transfer, excited-state lifetime, DNA melting and fluorescence
      quenching by ferrocyanide and sodium chloride. It is expected that the target
      pyrimidines cause berberine to be stacked well within DNA base pairs near the AP
      site, which results in a strong resonance coupling of the electronic transitions
      to the particular vibration mode to produce the dual emissions. The fluorescent
      signal-on and emission energy-modulated sensing for nucleobases based on this
      fluorophore is substantially advantageous over the previously used fluorophores.
      We expect that this approach will be developed as a practical device for
      differentiating pyrimidines from purines by positioning an AP site toward a
      target that is available for readout by this alkaloid probe.

PMID- 22410867
TI  - Integrating cryptococcal antigen screening and pre-emptive treatment into routine
      HIV care.
AB  - Cryptococcal meningitis is a leading cause of death in AIDS patients in sub
      Saharan Africa. Cryptococcal antigen (CRAG) can be detected weeks before onset of
      symptoms, and those who are asymptomatic but CRAG positive have a high risk of
      subsequent cryptococcal meningitis and mortality. A new CRAG point of care
      immunochromatographic test is available that is remarkably easy to administer
      without laboratory infrastructure or expertise and has excellent sensitivity and
      specificity. We review the benefits of targeted CRAG screening, developments in
      CRAG diagnostics, and evidence regarding treatment options that can be
      implemented into routine HIV care in areas of high cryptococcal burden. Based on
      published CRAG+ prevalence rates of 2%-12%, the cost to save one life is between
      $20 to $140 in sub-Saharan Africa. We provide recommendations for implementation,
      pre-emptive treatment, and identify the gaps in our current knowledge.

PMID- 22410868
TI  - Ectopic fat is linked to prior cardiovascular events in men with HIV.
AB  - Epicardial Adipose Tissue (EAT) has been associated with adverse cardiovascular
      events in the general population. We studied the association of general adiposity
      measures (body mass index, waist circumference) and ectopic adipose tissue
      [visceral adipose tissue (VAT); liver fat (LF); EAT) with prevalent
      cardiovascular disease (CVD) (prior myocardial infarction, coronary
      revascularization, stroke, peripheral vascular disease] in 583 HIV-infected men.
      VAT, EAT, and LF (liver/spleen attenuation ratio < 1.1) were measured by computed
      tomography. Patients' mean age was 48.5 +/- 8.1 years, prior CVD was present in
      33 (5.7%) patients. Factors independently associated with CVD on multivariable
      analyses were age [incidence-rate ratio (IRR) = 1.07, 95% confidence interval
      (CI): 1.02 to 1.12], smoking (IRR = 2.70, 95% CI: 1.22 to 6.01), Center for
      Disease Control group C (IRR = 3.09, 95% CI: 1.41 to 6.76), EAT (IRR = 1.13, 95%
      CI: 1.04 to 1.24, per 10 cm), LF (IRR = 1.17, 95% CI: 1.04 to 1.32), and VAT (IRR
      = 1.05, 95% CI: 1.00 to 1.10, per 10 cm). Ectopic fat but not general adiposity
      measures were associated with prevalent CVD in men with HIV.

PMID- 22410869
TI  - Minimally invasive male circumcision.

PMID- 22410871
TI  - Reply to "Clinical impact and cost of laboratory monitoring need review even in
      resource-rich setting".

PMID- 22410872
TI  - The interferons and their receptors--distribution and regulation.
AB  - The interferons (IFNs) were originally described over 50 years ago, identified by
      their ability to confer viral resistance to cells. We now know that they are much
      more than just anti-viral cytokines collectively having roles in both innate and
      adaptive immune responses, in tumor surveillance and defense, and modulation of
      immune cell function. Three types of IFN have now been described, simply referred
      to as type I, II and III. Distinguishable by the unique receptors that they rely
      on for signal transduction, the three types of IFN have specific and varied roles
      in the maintenance of human health and defense against pathogens. In mounting an
      IFN-mediated immune response, the human body has developed the ability to
      regulate IFN-mediated signal transduction. Like all cytokines, the ability of a
      cell to respond to IFN is completely dependent on the presence of its cognate
      receptor on the surface of the target cell. Thus, one of the major mechanisms
      used by the human body to regulate the strength and duration of the IFN response
      is through regulation of receptor levels, thereby altering the cytokine-specific
      responsiveness of the target cell. This review will discuss the receptor system
      utilized by the type I IFNs and compare it with that of the type II and III IFNs,
      which also regulate immune responses through controlling receptor level on the
      cell surface.

PMID- 22410873
TI  - Validation of membrane protein topology models by oxidative labeling and mass
      spectrometry.
AB  - Computer-assisted topology predictions are widely used to build low-resolution
      structural models of integral membrane proteins (IMPs). Experimental validation
      of these models by traditional methods is labor intensive and requires
      modifications that might alter the IMP native conformation. This work employs
      oxidative labeling coupled with mass spectrometry (MS) as a validation tool for
      computer-generated topology models. .OH exposure introduces oxidative
      modifications in solvent-accessible regions, whereas buried segments (e.g.,
      transmembrane helices) are non-oxidizable. The Escherichia coli protein WaaL (O
      antigen ligase) is predicted to have 12 transmembrane helices and a large
      extramembrane domain (Perez et al., Mol. Microbiol. 2008, 70, 1424). Tryptic
      digestion and LC-MS/MS were used to map the oxidative labeling behavior of WaaL.
      Met and Cys exhibit high intrinsic reactivities with .OH, making them sensitive
      probes for solvent accessibility assays. Overall, the oxidation pattern of these
      residues is consistent with the originally proposed WaaL topology. One residue
      (M151), however, undergoes partial oxidation despite being predicted to reside
      within a transmembrane helix. Using an improved computer algorithm, a slightly
      modified topology model was generated that places M151 closer to the membrane
      interface. On the basis of the labeling data, it is concluded that the refined
      model more accurately reflects the actual topology of WaaL. We propose that the
      combination of oxidative labeling and MS represents a useful strategy for
      assessing the accuracy of IMP topology predictions, supplementing data obtained
      in traditional biochemical assays. In the future, it might be possible to
      incorporate oxidative labeling data directly as constraints in topology
      prediction algorithms.

PMID- 22410875
TI  - CT-Enteroclysis in the preoperative assessment of the small-bowel involvement in
      patients with peritoneal carcinomatosis, candidates for cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy.
AB  - PURPOSE: To assess the performance of CT-Enteroclysis (CTE) in the preoperative
      evaluation of the small bowel (SB) involvement in patients with peritoneal
      carcinomatosis (PC), candidates for cytoreductive surgery (CRS) and hyperthermic
      intraperitoneal chemotherapy (HIPEC). MATERIAL AND METHODS: In this prospective
      study, 48 consecutive patients (37 women, 11 men, mean age: 57.02 years) with PC
      of different primaries, eligible for cytoreductive surgery and HIPEC underwent
      CTE before surgery. Lesions were gathered according to their location (SB wall or
      mesentery), distribution (jejunum/ileum, proximal/distal) and lesion size (LS,
      where LS0 is the absence of disease, LS1 < 1 cm, LS < 1-5 cm, and LS3 > 5 cm in
      maximal diameter). The preoperative CTE classification was correlated with
      surgical scoring of PC in the SB. RESULTS: CTE was found to have sensitivity 92%,
      specificity 96%, PPV 97%, NPV 91%, in assessing PC in the SB/mesentery. CTE
      exhibited "excellent" agreement with surgical classification of disease extent
      (overall kappa-weighted coefficient of agreement (kappa (w)) was 0.962). Patients
      (n = 6) found inoperable at surgery manifested extensive plaque-like cover of the
      SB wall/mesentery on CTE. CONCLUSIONS: CTE may be considered a reliable imaging
      technique for the preoperative evaluation of the extent and distribution of PC in
      the SB/mesentery in order to assist surgical planning or to prevent unnecessary
      surgery.

PMID- 22410874
TI  - Imposex reduction and residual butyltin contamination in southern Brazilian
      harbors.
AB  - The imposex incidence was appraised in South American gastropods, considering the
      scenario before and after the global ban of tributyltin (TBT). A statistically
      significant reduction in imposex indexes was observed in Stramonita haemastoma
      collected in 2006 and 2010 from areas under the influence of four coastal harbors
      from southern Brazil. This reduction may be because of the effectiveness of the
      global ban issued by the International Maritime Organization, although the
      restrictions on TBT-based antifouling paints in Brazil might also have helped.
      Even so, a residual organotin contamination was still detected in female tissues
      (levels ranged from 7.6 to 164.9 ng Sn/g for TBT; from <2 to 214.5 ng Sn/g for
      dibutyltin; from <3.5 to 178.8 ng Sn/g for monobutyltin; and from <1.5 to 53 ng
      Sn/g for triphenyltin). Thus, although a reduction in imposex and environmental
      levels of organotins is expected in every ocean worldwide soon after the
      implementation of national and international restriction regulations, this will
      depend on the effectiveness of the global TBT ban; the effectiveness of local
      restrictions on producing, selling, and using TBT-based antifouling paints; and
      specific characteristics of local sediments, because metabolization rates and
      sorption/desorption of TBT previously deposited might affect its environmental
      bioavailability. Therefore, the reduction trend detected in the present study
      cannot be extrapolated to other Brazilian or South American coastal areas.

PMID- 22410876
TI  - Multisystemic therapy reduces re-offending in young offenders between 12 and 18
      months post-treatment.

PMID- 22410878
TI  - Bidimensional fluorescence analysis and thermal design of europium
      thenoyltrifluoroacetonate based thermal-to-visible converter.
AB  - We perform a bidimensional analysis to evaluate the variation of the fluorescence
      decay of europium thenoyltrifluoroacetonate (EuTTA) with temperature changes. We
      analyze how a specific thermal distribution modifies the spatial temperature of
      the sensing film and we study the corresponding fluorescence response using an
      integral functional of the emission decay. We present experimental results of a
      thermal distribution registered with the EuTTA-based thermal-to-visible
      conversion method. Furthermore, we analyze the spatial and temporal response of
      the proposed sensing element by using heat-transfer theory. Based on the
      presented analysis, we establish the optimal thermal and physical design for the
      sensing element of the proposed thermal-to-visible converter.

PMID- 22410877
TI  - Subclinical hypothyroidism, mood, and cognition in older adults: a review.
AB  - OBJECTIVES: To perform a critical review of the literature on the mood and
      cognitive changes associated with subclinical hypothyroidism (SCH), with an
      emphasis on older adults. To evaluate these data against the Consensus Statement
      on the management of SCH from the American Association of Clinical
      Endocrinologists, the American Thyroid Association, and The Endocrine Society.
      METHOD: A comprehensive literature review. RESULTS: Subclinical hypothyroidism
      may be associated with an increased risk of mood and cognitive dysfunction,
      although the strength of this association and the efficacy of replacement hormone
      therapy require further investigation. CONCLUSION: It remains unclear whether SCH
      leads to significant mood and cognitive impairments in most older patients. More
      research is required to determine the nature and extent of this association and
      whether thyroid hormone replacement therapy is appropriate and effective in
      treating SCH-associated neurobehavioral impairments.

PMID- 22410879
TI  - System integration and radiation pattern measurements of a phased array antenna
      employing an integrated photonic beamformer for radio astronomy applications.
AB  - In this paper we describe the system integration and the experimental
      demonstration of a photonically beamformed four-element receiving array antenna
      for radio astronomy applications. To our knowledge, the work described here is
      the first demonstration of the squint-free, continuously tunable beamsteering
      capability offered by an integrated photonic beamformer based on optical ring
      resonator true-time-delay units, with measured radiation patterns. The integrated
      beamformer is realized in a low loss, complementary metal-oxide-semiconductor
      (CMOS) compatible optical waveguide technology. The measurements show a wideband,
      continuous beamsteering operation over a steering angle of 23.5 degrees and an
      instantaneous bandwidth of 500 MHz limited only by the measurement setup.

PMID- 22410880
TI  - Tea classification and quality assessment using laser-induced fluorescence and
      chemometric evaluation.
AB  - Laser-induced fluorescence was used to evaluate the classification and quality of
      Chinese oolong teas and jasmine teas. The fluorescence of four different types of
      Chinese oolong teas-Guangdong oolong, North Fujian oolong, South Fujian oolong,
      and Taiwan oolong was recorded and singular value decomposition was used to
      describe the autofluoresence of the tea samples. Linear discriminant analysis was
      used to train a predictive chemometric model and a leave-one-out methodology was
      used to classify the types and evaluate the quality of the tea samples. The
      predicted classification of the oolong teas and the grade of the jasmine teas
      were estimated using this method. The agreement between the grades evaluated by
      the tea experts and by the chemometric model shows the potential of this
      technique to be used for practical assessment of tea grades.

PMID- 22410881
TI  - The Diffuse Interstellar Cloud Experiment: a high-resolution far-ultraviolet
      spectrograph.
AB  - We have designed, assembled, and launched a sounding rocket payload to perform
      high-resolution far-ultraviolet spectroscopy. The instrument is functionally a
      Cassegrain telescope followed by a modified Rowland spectrograph. The
      spectrograph was designed to achieve a resolving power (R=lambda/deltalambda) of
      60,000 in a compact package by adding a magnifying secondary optic. This is
      enabled by using a holographically ruled grating to minimize aberrations induced
      by the second optic. We designed the instrument to observe two stars on opposing
      sides of a nearby hot/cold gas interface. Obtaining spectra of the O VI doublet
      in absorption toward these stars can provide new insight into the processes
      governing hot gas in the local interstellar medium. Here we present the optical
      design and alignment of the telescope and spectrograph, as well as flight
      results.

PMID- 22410882
TI  - Quantitative measurement of the orbital angular momentum density of light.
AB  - In this work we derive expressions for the orbital angular momentum (OAM) density
      of light, for both symmetric and nonsymmetric optical fields, that allow a direct
      comparison between theory and experiment. We present a simple method for
      measuring the OAM density in optical fields and test the approach on superimposed
      nondiffracting higher-order Bessel beams. The measurement technique makes use of
      a single spatial light modulator and a Fourier transforming lens to measure the
      OAM spectrum of the optical field. Quantitative values for the OAM density as a
      function of the radial position in the optical field are obtained for both
      symmetric and nonsymmetric superpositions, illustrating good agreement with the
      theoretical prediction.

PMID- 22410883
TI  - High-spectral-flatness mid-infrared supercontinuum generated from a Tm-doped
      fiber amplifier.
AB  - Broadband mid-infrared supercontinuum pulses were generated directly from a short
      piece of active fiber in a single-mode Tm-doped fiber amplifier. The broadband
      mid-infrared pulses have an extremely high spectral flatness with ~600 nm FWHM
      bandwidth (from 1.9 MUm to 2.5 MUm), >15 kW peak power, and >20 GW/cm(2) laser
      peak intensity. This new approach exhibits a significantly different physical
      mechanism from other supercontinuum generation demonstrations in the literature,
      in which usually a piece of passive fiber was used for nonlinear spectral
      broadening. The physical mechanism for the broadband mid-infrared supercontinuum
      generation in this approach has been attributed to a combined effect of two
      superradiative processes of Tm(3+) ions (i.e., the (3)F(4)-(3)H(6) transition
      covering the 1.8~2.1  MUm spectral region and the (3)H(4)-(3)H(5) transition
      covering the 2.2~2.5  MUm spectral region), and also nonlinear optical processes
      as well in the Tm-doped gain fiber. The spectra of the mid-infrared
      supercontinuum pulses were further broadened in a 2 m chalcogenide fiber with 20
      dB bandwidth ~1100 nm and a 3 m fluoride fiber with 20 dB bandwidth ~2600 nm.

PMID- 22410884
TI  - Stereo vision calibration based on GMDH neural network.
AB  - In order to improve the accuracy and stability of stereo vision calibration, a
      novel stereo vision calibration approach based on the group method of data
      handling (GMDH) neural network is presented. Three GMDH neural networks are
      utilized to build a spatial mapping relationship adaptively in individual
      dimension. In the process of modeling, the Levenberg-Marquardt optimization
      algorithm is introduced as an interior criterion to train each partial model, and
      the corrected Akaike's information criterion is introduced as an exterior
      criterion to evaluate these models. Experiments demonstrate that the proposed
      approach is stable and able to calibrate three-dimensional (3D) locations more
      accurately and learn the stereo mapping models adaptively. It is a convenient way
      to calibrate the stereo vision without specialized knowledge of stereo vision.

PMID- 22410885
TI  - Multiangle dynamic light scattering analysis using angular intensity weighting
      determined by iterative recursion.
AB  - Multiangle dynamic light scattering (MDLS) can provide better results for
      particle size distribution (PSD) determination than single-angle dynamic light
      scattering. Proper analysis of MDLS data requires data from each measurement
      angle to be appropriately weighted according to the intensity scattered by the
      particles at each scattering angle. The angular weighting coefficients may be
      determined by measuring the angular dependence of the scattered light intensity
      or estimated in various ways. In either case, any noise on the weighting
      coefficients will adversely affect the PSD determination. We propose a new
      iterative recursion method for estimating the weighting coefficients and
      demonstrate its effectiveness for recovering PSDs from both simulated and real
      experimental data. The new method gives better PSD results than those found using
      other weighting estimates.

PMID- 22410886
TI  - Rapid optimization of cost-based tolerancing.
AB  - In this paper, a rapid optimization method of cost-based tolerancing is proposed.
      An example shows that only a few cases of the Monte Carlo simulation are
      necessary to find the best balance of the yield and the tolerance cost for the
      practical tolerancing problem.

PMID- 22410887
TI  - Comparison of the squared binary, sinusoidal pulse width modulation, and optimal
      pulse width modulation methods for three-dimensional shape measurement with
      projector defocusing.
AB  - This paper presents a comparative study on three sinusoidal fringe pattern
      generation techniques with projector defocusing: the squared binary defocusing
      method (SBM), the sinusoidal pulse width modulation (SPWM) technique, and the
      optimal pulse width modulation (OPWM) technique. Because the phase error will
      directly affect the measurement accuracy, the comparisons are all performed in
      the phase domain. We found that the OPWM almost always performs the best, and
      SPWM outperforms SBM to a great extent, while these three methods generate
      similar results under certain conditions. We will briefly explain the principle
      of each technique, describe the optimization procedures for each technique, and
      finally compare their performances through simulations and experiments.

PMID- 22410888
TI  - Generation of high-order optical vortices using directly machined spiral phase
      mirrors.
AB  - We report on the generation of high-order optical vortices by spiral phase
      mirrors (SPMs). The mirrors are produced by direct machining with a diamond tool
      and are shown to produce high-quality optical vortices with topological charges
      ranging from 1 to upwards of 100 at a wavelength of 532 nm. The direct machining
      technique is flexible and offers the promise of high-precision, large-diameter
      SPMs that are compatible with high optical powers.

PMID- 22410889
TI  - Binary blazed grating based on autostereoscopic display mechanism.
AB  - The diffractive optical element blazed grating is proposed as the beam splitter
      for autostereoscopic displays in this study. With Lithographie Galvanoformung
      Abformung and inductively coupled plasma reactive-ion etching, a four-level
      blazed grating structure is produced. Moreover, highly translucent
      polydimethylsiloxane is transformed into symmetrical four-level blazed grating
      films. The experimental results show that the film can successfully transmit the
      left and the right images to the accurate positions, and the diffraction
      efficiency is 70.4% and the contrast ratio is above 80%, presenting the original
      stereoscopic image without it being affected by brightness and crosstalk. In the
      experiment of stereoscopic imaging, both the left and the right images could be
      clearly acquired, which proves the feasibility of blazed gratings as practical
      for the beam splitter of autostereoscopic displays.

PMID- 22410890
TI  - Measurement device for noise factor of microchannel plate.
AB  - A new method for noise power factor determination of microchannel plates (MCPs)
      is described in this paper. The new measuring condition and specific measuring
      instrument are reported. The system consists of a vacuum chamber, an electron
      gun, a high-voltage supply, an imaging luminance meter, control units, a signal
      processing circuit, an A/D converter, a D/A converter, a communication unit, an
      industrial computer, and measurement software. This measuring method fills a void
      in measuring technology for the noise factor of MCPs, and it can make a
      scientific assessment of MCP noise characteristics and provide theoretical
      direction and technology support for the research and development of high
      performance low light level (LLL) devices.

PMID- 22410891
TI  - Locking phenomenon of polarization flipping in He-Ne laser with a phase
      anisotropy feedback cavity.
AB  - In this article, the locking phenomenon of polarization flipping is reported. A
      model that integrates the model of the equivalent cavity of a Fabry-Perot
      interferometer and Lamb's semiclassical theory is built to explain the locking
      phenomenon. On the basis of analysis of the model, a method is proposed to
      release the locking of polarization flipping. After solving the problem of lock
      in, the system in this paper can be used to measure small stress of the optical
      component and phase retardation of the birefringence component.

PMID- 22410892
TI  - Schottky barrier characteristics and internal gain mechanism of TiO2 UV
      detectors.
AB  - High-responsivity metal-semiconductor-metal TiO(2) UV photodetectors with Ni and
      Au electrodes were fabricated identically. Their Schottky barrier heights and
      photocurrent gain mechanism were studied. The effective barrier height Phi and
      ideality factor n were evaluated according to the thermionic emission theory. The
      result that Phi(Ni) was lower than Phi(Au) may be attributed to the electron
      transfer from Ni to the TiO(2) substrate, which would lead to a dipole layer and,
      accordingly, decrease the barrier height. In addition, the I-V characteristics of
      the Ni/TiO(2)/Ni and Au/TiO(2)/Au photodetectors were observed. A significant
      internal gain was obtained, and the mechanism of the internal gain was studied by
      the phototransistor model in detail.

PMID- 22410893
TI  - Polarization-independent optical circulator for high accuracy Faraday
      depolarization lidar.
AB  - A high precision, polarization-independent optical circulator was developed for
      high accuracy Faraday depolarization lidar. Glan laser prisms and other novel
      optics were utilized in the circulator optics, resulting in a high extinction
      ratio of polarization of >30 dB. High accuracy is needed to detect a small
      rotation angle in the polarization plane of the propagating beam. It is generated
      by the Faraday effect due to the lightning discharge. The developed circulator
      delivered high performance of insertion loss and isolation as laser transmitter
      and echo receiver in the inline lidar optics.

PMID- 22410894
TI  - Optical pressure sensor based on the combined system of a variable liquid lens
      and a point diffraction interferometer.
AB  - We propose an experimental efficient optical pressure sensor based on a variable
      liquid lens and a modified point diffraction interferometer. The working
      principle of the sensor is based on the fact that a variation in pressure induces
      a change in lens curvature and hence in its focal length, which can be tracked
      and measured with the interferometer. The pressure is then measured by recording
      and processing the interferometric images. The sensor in this proposal can change
      its dynamic range by the simple axial movement of one of the components of the
      optical system. In this work we show the performance of the system within three
      working ranges: from 0 to 1 kPa with accuracy of approximately 0.01 kPa, from 0
      to 7 kPa with 0.05 kPa accuracy, and from 0 to 30 kPa with 0.3 kPa accuracy.

PMID- 22410895
TI  - Design and experimental verification of terahertz wideband filter based on double
      layered metal hole arrays.
AB  - A terahertz wideband filter based on double layer metal hole arrays is designed
      in this paper. A metal hole array is perforated on a metal layer with a square
      array of circular air holes. The transmission characteristics of the
      electromagnetic waves through the metal hole array can be determined by the
      accumulation of in-phase scattering, spoof surface plasmon polaritons, and
      waveguide modes. The transmission spectrum is tuned by adding another identical
      layer metal hole array, and a wideband filter can be formed accordingly. Samples
      containing double-layered metal hole arrays were fabricated by micromachining
      technology. A wideband filter with center frequency located at 0.8 THz and FWHM
      reaching 400 GHz was experimentally achieved.

PMID- 22410896
TI  - Design and implementation of the one-step MSD adder of optical computer.
AB  - On the basis of the symmetric encoding algorithm for the modified signed-digit
      (MSD), a 7*7 truth table that can be realized with optical methods was developed.
      And based on the truth table, the optical path structures and circuit
      implementations of the one-step MSD adder of ternary optical computer (TOC) were
      designed. Experiments show that the scheme is correct, feasible, and efficient.

PMID- 22410897
TI  - Origin of particles during reactive sputtering of oxides using planar and
      cylindrical magnetrons.
AB  - Particles generated during reactive magnetron sputtering cause defects in optical
      thin films, which may lead to losses in optical performance, pinholes, loss of
      adhesion, decreased laser-induced damage thresholds and many more negative
      effects. Therefore, it is important to reduce the particle contamination during
      the manufacturing process. In the present paper, the origin of particles during
      the deposition of various oxide films by midfrequency pulsed reactive magnetron
      sputtering was investigated. Several steps have been undertaken to decrease the
      particle contamination during the complete substrate handling procedure. It was
      found that conditioning of the vacuum chamber can help to decrease the defect
      level significantly. This level remains low for several hours of sputtering and
      increases after 100 hours of process time. Particle densities of SiO(2) films
      deposited with cylindrical and planar dual magnetrons at different process
      parameters as well as different positions underneath the target were compared. It
      was observed that the process power influences the particle density significantly
      in case of planar targets while cylindrical targets have no such strong
      dependence. In addition, the particle contamination caused by different
      cylindrical target materials was analyzed. No major differences in particle
      contamination of different cylindrical target types and materials were found.

PMID- 22410898
TI  - Robust camera pose estimation from unknown or known line correspondences.
AB  - We address the model-to-image registration problem with line features in the
      following two ways. (a) We present a robust solution to simultaneously recover
      the camera pose and the three-dimensional-to-two-dimensional line
      correspondences. With weak pose priors, our approach progressively verifies the
      pose guesses with a Kalman filter by using a subset of recursively found match
      hypotheses. Experiments show our method is robust to occlusions and clutter. (b)
      We propose a new line feature based pose estimation algorithm, which iteratively
      optimizes the objective function in the object space. Experiments show that the
      algorithm has strong robustness to noise and outliers and that it can attain very
      accurate results efficiently.

PMID- 22410899
TI  - Fiber-based device for the detection of low-intensity fluctuations of ultrashort
      pulses.
AB  - We describe a fiber-based device that can significantly enhance the low-intensity
      fluctuations of an ultrashort pulse train to detect them more easily than with
      usual direct detection systems. Taking advantage of the Raman intrapulse effect
      that progressively shifts the central frequency of a femtosecond pulse
      propagating in an anomalous dispersion fiber, a subsequent spectral filtering can
      efficiently increase the level of fluctuations by more than 1 order of magnitude.
      We show that attention has to be paid to maintain the shape of the statistical
      distribution unaffected by the nonlinear process.

PMID- 22410900
TI  - Formation of transverse mode in axially symmetric lasers.
AB  - The developed iteration algorithm for simulation of lasers with an open resonator
      was employed in the study of transverse mode formation. The simulations of an
      axially symmetrical resonator rely on an analytical description of radiation
      diffraction from a narrow ring. Reflection of an incident wave with a specified
      amplitude-phase distribution from the mirror is calculated by the Green-function
      method. The model also includes an active medium homogeneous along the resonator
      axis that is represented by the formula for saturating gain. The calculations
      were performed for two types of lasers: with on-axis and off-axis gain maximum.
      In the first type of laser one can obtain either a principal mode or "multimode"
      generation. The latter means quasi-stationary generation with regular or chaotic
      oscillations. In the second type of laser high order single-mode generation is
      possible. Experimental results obtained on a fast axial flow 4 kW CO(2) laser are
      also presented. They are in good agreement with the calculations.

PMID- 22410901
TI  - Three-dimensional tomographic reconstruction of mesospheric airglow structures
      using two-station ground-based image measurements.
AB  - A new methodology is presented to create two-dimensional (2D) and three
      dimensional (3D) tomographic reconstructions of mesospheric airglow layer
      structure using two-station all-sky image measurements. A fanning technique is
      presented that produces a series of cross-sectional 2D reconstructions, which are
      combined to create a 3D mapping of the airglow volume. The imaging configuration
      is discussed and the inherent challenges of using limited-angle data in
      tomographic reconstructions have been analyzed using artificially generated
      imaging objects. An iterative reconstruction method, the partially constrained
      algebraic reconstruction technique (PCART), was used in conjunction with a priori
      information of the airglow emission profile to constrain the height of the imaged
      region, thereby reducing the indeterminacy of the inverse problem. Synthetic
      projection data were acquired from the imaging objects and the forward problem to
      validate the tomographic method and to demonstrate the ability of this technique
      to accurately reconstruct information using only two ground-based sites.
      Reconstructions of the OH airglow layer were created using data recorded by all
      sky CCD cameras located at Bear Lake Observatory, Utah, and at Star Valley,
      Wyoming, with an optimal site separation of ~100 km. The ability to extend
      powerful 2D and 3D tomographic methods to two-station ground-based measurements
      offers obvious practical advantages for new measurement programs. The importance
      and applications of mesospheric tomographic reconstructions in airglow studies,
      as well as the need for future measurements and continued development of
      techniques of this type, are discussed.

PMID- 22410902
TI  - Multilevel, hybrid regularization method for reconstruction of fluorescent
      molecular tomography.
AB  - In this paper, a multilevel, hybrid regularization method is presented for
      fluorescent molecular tomography (FMT) based on the hp-finite element method (hp
      FEM) with a continuous wave. The hybrid regularization method combines sparsity
      regularization and Landweber iterative regularization to improve the stability of
      the solution of the ill-posed inverse problem. In the first coarse mesh level,
      considering the fact that the fluorescent probes are sparsely distributed in the
      entire reconstruction region in most FMT applications, the sparse regularization
      method is employed to take full advantage of this sparsity. In the subsequent
      refined mesh levels, since the reconstruction region is reduced and the initial
      value of the unknown parameters is provided from the previous mesh, these mesh
      levels seem to be different from the first level. As a result, the Landweber
      iterative regularization method is applied for reconstruction. Simulation
      experiments on a 3D digital mouse atlas and physical experiments on a phantom are
      conducted to evaluate the performance of our method. The reconstructed results
      show the potential and feasibility of the proposed approach.

PMID- 22410903
TI  - Fast M2 measurement for fiber beams based on modal analysis.
AB  - We report on a fast and experimentally easy technique for measuring the beam
      propagation ratio M(2) of light guided by optical fibers. A holographic filter
      enables us to determine amplitudes and phases of the excited fiber eigenmodes.
      The coherent superposition of modes allows the reconstruction of the optical
      field. With this information at hand, we are able to simulate the free-space
      propagation of the beam and to perform a virtual caustic measurement. Associated
      beam propagation ratios M(2) accurately agree with ISO-standard measurements.

PMID- 22410904
TI  - Circular Dammann grating under high numerical aperture focusing.
AB  - Circular Dammann grating (CDG) under high numerical aperture (NA) focusing is
      described based on Richards-Wolf vectorial diffraction theory in this paper.
      Several CDGs are presented under the condition of NA=0.9 with the illumination of
      circularly polarized plane-wave laser beams. Numerical results show that the
      sizes of these circular patterns with equal-intensity are in the wavelength
      scale, and doughnut-shaped central spots and dark rings are in the subwavelength
      width. To verify this kind of CDG, a binary pure-phase three-order CDG is
      fabricated to produce a dark center pattern surrounded by three concentric bright
      rings. The corresponding intensity distribution of the pattern on the focal plane
      of a high-NA objective (NA=0.9) is measured, and the results agree well with
      theoretical simulations. This kind of CDG with annular patterns of equal
      intensity in the wavelength scale should be highly interesting for its potential
      applications in optical trapping, stimulated emission depletion (STED)
      microscopy, and the study of singular optics, as well as annular array
      illumination.

PMID- 22410905
TI  - Multiple-image encryption by compressive holography.
AB  - We present multiple-image encryption (MIE) based on compressive holography. In
      the encryption, a holographic technique is employed to record multiple images
      simultaneously to form a hologram. The two-dimensional Fourier data of the
      hologram are then compressed by nonuniform sampling, which gives rise to
      compressive encryption. Decryption of individual images is cast into a
      minimization problem. The minimization retains the sparsity of recovered images
      in the wavelet basis. Meanwhile, total variation regularization is used to
      preserve edges in the reconstruction. Experiments have been conducted using
      holograms acquired by optical scanning holography as an example. Computer
      simulations of multiple images are subsequently demonstrated to illustrate the
      feasibility of the MIE scheme.

PMID- 22410906
TI  - Analysis of time-resolved superposed atomic hydrogen Balmer lines and molecular
      diatomic carbon spectra.
AB  - We present analysis of superposition spectra following laser-induced breakdown
      (LIB) of methane. Both hydrogen-beta and hydrogen-gamma lines contain discernible
      contributions from diatomic carbon emissions for time delays of 1 to 2 MUs from
      pulsed, 8 ns, infrared Nd:YAG laser radiation LIB. Analysis of the atomic lines
      and molecular C(2) spectra reveal electron and molecular excitation temperatures
      of typically 13,000 and 5000 K, respectively.

PMID- 22410907
TI  - Construction of a predictive model for concentration of nickel and vanadium in
      vacuum residues of crude oils using artificial neural networks and LIBS.
AB  - A predictive model to determine the concentration of nickel and vanadium in
      vacuum residues of Colombian crude oils using laser-induced breakdown
      spectroscopy (LIBS) and artificial neural networks (ANNs) with nodes distributed
      in multiple layers (multilayer perceptron) is presented. ANN inputs are intensity
      values in the vicinity of the emission lines 300.248, 301.200 and 305.081 nm of
      the Ni(I), and 309.310, 310.229, and 311.070 nm of the V(II). The effects of
      varying number of nodes and the initial weights and biases in the ANNs were
      systematically explored. Average relative error of calibration/prediction
      (REC/REP) and average relative standard deviation (RSD) metrics were used to
      evaluate the performance of the ANN in the prediction of concentrations of two
      elements studied here.

PMID- 22410908
TI  - Analysis of the absorption layer of CIGS solar cell by laser-induced breakdown
      spectroscopy.
AB  - Laser induced breakdown spectroscopy (LIBS) was applied for the elemental
      analysis of the thin copper indium gallium diselenide (CuIn(1-x)Ga(x)Se(2)
      [CIGS]) absorption layer deposited on Mo-coated soda-lime glass by the co
      evaporation technique. The optimal laser and detection parameters for LIBS
      measurement of the CIGS absorption layer (1.23 MUm) were investigated. The
      calibration results of Ga/In ratio with respect to the concentration ratios
      measured by x-ray fluorescence and inductively coupled plasma optical emission
      spectroscopy showed good linearity.

PMID- 22410909
TI  - Comparative study of Nd:YAG laser-induced breakdown spectroscopy and transversely
      excited atmospheric CO2 laser-induced gas plasma spectroscopy on chromated copper
      arsenate preservative-treated wood.
AB  - Taking advantage of the specific characteristics of a transversely excited
      atmospheric (TEA) CO(2) laser, a sophisticated technique for the analysis of
      chromated copper arsenate (CCA) in wood samples has been developed. In this
      study, a CCA-treated wood sample with a dimension of 20 mm * 20 mm and a
      thickness of 2 mm was attached in contact to a nickel plate (20 mm * 20 mm * 0.15
      mm), which functions as a subtarget. When the TEA CO(2) laser was successively
      irradiated onto the wood surface, a hole with a diameter of approximately 2.5 mm
      was produced inside the sample and the laser beam was directly impinged onto the
      metal subtarget. Strong and stable gas plasma with a very large diameter of
      approximately 10 mm was induced once the laser beam had directly struck the metal
      subtarget. This gas plasma then interacted with the fine particles of the sample
      inside the hole and finally the particles were effectively dissociated and
      excited in the gas plasma region. By using this technique, high precision and
      sensitive analysis of CCA-treated wood sample was realized. A linear calibration
      curve of Cr was successfully made using the CCA-treated wood sample. The
      detection limits of Cr, Cu, and As were estimated to be approximately 1, 2, and
      15 mg/kg, respectively. In the case of standard LIBS using the Nd:YAG laser, the
      analytical intensities fluctuate and the detection limit was much lower at
      approximately one-tenth that of TEA CO(2) laser.

PMID- 22410910
TI  - Laser-induced plasma chemistry of the explosive RDX with various metallic
      nanoparticles.
AB  - The feasibility of exploiting plasma chemistry to study the chemical reactions
      between metallic nanoparticles and molecular explosives such as
      cyclotrimethylenetrinitramine (RDX) has been demonstrated. This method, based on
      laser-induced breakdown spectroscopy, involves the production of nanoparticles in
      a laser-induced plasma and the simultaneous observation of time-resolved atomic
      and molecular emission characteristic of the species involved in the intermediate
      chemical reactions of the nanoenergetic material in the plasma. Using this
      method, it has been confirmed that the presence of aluminum promotes the ejection
      process of carbon from the intermediate products of RDX. The time evolution of
      species formation, the effects of laser pulse energy, and the effects of trace
      metal content on the chemical reactions were also studied.

PMID- 22410911
TI  - Comparison of two partial least squares-discriminant analysis algorithms for
      identifying geological samples with the ChemCam laser-induced breakdown
      spectroscopy instrument.
AB  - ChemCam, a laser-induced breakdown spectroscopy (LIBS) instrument on the Mars
      Science Laboratory rover, will analyze the chemistry of the martian surface
      beginning in 2012. Prior to integration on the rover, the ChemCam instrument
      collected data on a variety of rock types to provide a training set for analysis
      of data from Mars. Models based on calibration data can be used to classify rocks
      via multivariate statistical techniques such as partial least squares
      discriminant analysis (PLS-DA). In this study, we employ a version of PLS-DA in
      which modeling is applied in a defined classification flow to a variety of
      geological materials and compare the results with the traditional PLS-DA
      technique. Results show that the modified algorithm is more effective at
      classifying samples.

PMID- 22410912
TI  - Determination of elemental impurities in plastic calibration standards using
      laser-induced breakdown spectroscopy.
AB  - Dual-energy computed tomography (CT) scanning is a rapidly emerging imaging
      technique employed in nondestructive evaluation of various materials. CT has been
      used for characterizing rocks and visualizing multiphase flow through rocks for
      over 25 years. The most common technique for dual-energy CT scanning relies on
      homogeneous calibration standards to produce the most accurate decoupled data.
      However, the use of calibration standards with impurities increases the
      probability of error in the reconstructed data and results in poor rock
      characterization. Laser-induced breakdown spectroscopy was used to determine
      impurity concentration in a set of commercially purchased calibration standards
      used in dual-energy scanning for material identification with coal samples. Two
      calibration models were developed by using univariate calibration with the
      internal ratio method and multiple linear regression. Seven elements (Al, Fe, Mg,
      Na, Ni, Sr, and Ti) were examined in five different samples containing varying
      amounts of each ion to compare calibration from univariate data analysis and from
      multivariate data analysis. The contaminant concentrations were also measured by
      a commercially available inductively coupled plasma optical emission spectroscopy
      instrument, and the data were used as a reference in developing calibration
      curves for a modified version of the single linear regression model and the
      multiple linear regression model.

PMID- 22410913
TI  - Application of laser-induced breakdown spectroscopy for total carbon
      quantification in soil samples.
AB  - The increase of greenhouse gas (i.e., CO(2)) levels in the atmosphere has caused
      noticeable climate change. Many nations are currently looking into methods of
      permanent underground storage for CO(2) in an attempt to mitigate this problem.
      The goal of this work is to develop a process for studying the total carbon
      content in soils before, during, and after CO(2) injection to ensure that no
      leakage is occurring or to determine how much is leaking if it is occurring and
      what effect it will have on the ecosystem between the injection formation and the
      atmosphere. In this study, we quantitatively determine the total carbon
      concentration in soil using laser-induced breakdown spectroscopy (LIBS). A soil
      sample from Starkville, Mississippi, USA was mixed with different amounts of
      carbon powder, which was used as a calibration for additional carbon in soil.
      Test samples were prepared by adding different but known amounts of carbon powder
      to a soil sample and then mixing with polyvinyl alcohol binder before being
      pressed into pellets. LIBS spectra of the test samples were collected and
      analyzed to obtain optimized conditions for the measurement of total carbon in
      soil with LIBS. The total carbon content in the samples was also measured by a
      carbon analyzer, and the data (average of triplicates) were used as a reference
      in developing calibration curves for a modified version of the single linear
      regression model and the multiple linear regression model. The calibration data
      were then used to determine the total carbon concentration of an unknown sample.
      This work is intended to be used in the initial development of a miniaturized,
      field-portable LIBS analyzer for CO(2) leak detection.

PMID- 22410914
TI  - Automated interpretation of LIBS spectra using a fuzzy logic inference engine.
AB  - Automated interpretation of laser-induced breakdown spectroscopy (LIBS) data is
      necessary due to the plethora of spectra that can be acquired in a relatively
      short time. However, traditional chemometric and artificial neural network
      methods that have been employed are not always transparent to a skilled user. A
      fuzzy logic approach to data interpretation has now been adapted to LIBS spectral
      interpretation. Fuzzy logic inference rules were developed using methodology that
      includes data mining methods and operator expertise to differentiate between
      various copper-containing and stainless steel alloys as well as unknowns. Results
      using the fuzzy logic inference engine indicate a high degree of confidence in
      spectral assignment.

PMID- 22410915
TI  - Practical high-resolution detection method for laser-induced breakdown
      spectroscopy.
AB  - A Fabry-Perot etalon was coupled to a Czerny-Turner spectrometer to acquire high
      resolution measurements in laser-induced breakdown spectroscopy (LIBS). The
      spectrometer was built using an inexpensive etalon coupled to a standard 0.5 m
      imaging spectrometer. The Hg emission doublet at 313.2 nm was used to evaluate
      instrument performance because it has a splitting of 29 pm. The 313.2 nm doublet
      was chosen due to the similar splitting seen in isotope splitting from uranium at
      424.437 nm, which is 25 pm. The Hg doublet was easily resolved from a continuous
      source Hg lamp with a 2 s acquisition. The doublet was also resolved in LIBS
      spectra of cinnabar (HgS) from the accumulation of 600 laser shots at rate of 10
      Hz, or 1 min, under a helium atmosphere. In addition to the observed splitting of
      the 313.2 nm Hg doublet, the FWHM of the 313.1844 nm line from the doublet is
      reported at varying helium atmospheric pressures. The high performance, low cost,
      and compact footprint make this system highly competitive with 2 m double-pass
      Czerny-Turner spectrometers.

PMID- 22410916
TI  - Helium detection in gas mixtures by laser-induced breakdown spectroscopy.
AB  - Laser-induced breakdown spectroscopy (LIBS) has been evaluated as a tool for
      monitoring trace levels of helium in gas mixtures consisting mostly of hydrogen.
      Calibration data for helium in hydrogen was investigated at different helium
      concentration levels. At high concentrations of helium (>7.25%), the LIBS signal
      is quenched due to Penning ionization. The hydrogen alpha line (656.28 nm) was
      observed to broaden as the concentration of helium impurities in the hydrogen gas
      mixture increased. The helium line at 587.56 nm was selected as the analyte line
      for helium impurity detection. The effects of laser energy, the delay time
      between the laser pulse and data acquisition, and the gas pressure on the LIBS
      signal of helium were investigated to determine the optimum conditions for helium
      detection. The LIBS signal from the helium line at 587.56 nm shows good linear
      correlation with helium concentration for He concentrations below 1%. Thus, LIBS
      can be reliably used to detect the low levels of helium. The limit of detection
      for helium was found to be 78 ppm.

PMID- 22410917
TI  - Spark-induced breakdown spectroscopy and multivariate analysis applied to the
      measurement of total carbon in soil.
AB  - Identifying and implementing techniques for carbon management has become an
      important endeavor in the mitigation of global climate change. Two important
      techniques being pursued are geologic and terrestrial carbon sequestration. With
      regard to terrestrial sequestration, in order to accurately monitor changes in
      soil carbon potentially induced by sequestration practices, rapid, cost
      effective, and accurate measurements must be developed. Spark-induced breakdown
      spectroscopy (SIBS) has the potential to be used as a field-deployable method to
      monitor changes in the concentration of carbon in soil. SIBS spectra in the 248
      nm region of eight soils were collected, and the neutral carbon line at 247.85 nm
      was compared to total carbon concentration determined by standard dry combustion
      techniques. Additionally, Fe and Si emission lines were evaluated in a
      multivariate statistical model to evaluate their impacts on the model's
      predictive power for total carbon concentrations. The preliminary results
      indicate that SIBS is a viable method to quantify total carbon levels in soils,
      obtaining a correlation of (R(2)=0.972) between measured and predicated carbon in
      soils. These results show that multivariate analysis can be used to construct a
      calibration model for SIBS soil spectra.

PMID- 22410918
TI  - Characteristics of microwave plasma induced by lasers and sparks.
AB  - Characteristics of the plasma light source of microwave (MW) plus laser-induced
      breakdown spectroscopy (LIBS) or spark-induced breakdown spectroscopy (SIBS) were
      studied. The plasma was initially generated by laser- or spark-induced breakdown
      as a plasma seed. A plasma volume was then grown and sustained by MWs in air.
      This MW plasma had a long lifetime, large volume, strong emission intensity, and
      high stability with time. These characteristics are suitable for applications in
      the molecular analysis of gases such as OH or N(2). Because the plasma properties
      did not depend on laser or spark plasma seeds, the resulting plasma was easily
      controllable by the input power and duration of the MWs. Therefore, a significant
      improvement was achieved in the spectral intensity and signal-to-noise ratio. For
      example, the peak intensity of the Pb spectra of LIBS increased 15 times, and
      that of SIBS increased 880 times without increases in their background noise. A
      MW-enhanced plasma light source could be used to make the total system smaller
      and cheaper than a conventional LIBS system, which would be useful for real-time
      and in situ analysis of gas molecules in, for example, food processing, medical
      applications, chemical exposure, and gas turbine or automobile air-to-fuel ratio
      and exhaust gas measurement.

PMID- 22410919
TI  - Stoichiometric investigations of laser-ablated brass plasma.
AB  - Laser-ablated brass plasma plumes expanding in various air pressures have been
      studied using optical emission spectroscopy and two-dimensional imaging. The
      velocity of the plume front calculated from the R-t plot decreases from 1.9*10(4)
      m/s to ~5.5*10(3) m/s as the pressure increases from 0.01 to 10(5) Pa. The
      estimated higher electron temperature for Cu I (510.5 nm) transition than for Zn
      I (481.1 nm) may be due to differences in the heat of vaporization and
      vaporization temperature of copper and zinc. The electron density estimated using
      the Stark-broadened transition 4p(2)P(3/2)->4s(2)(2)D(5/2) of Cu I (510.5 nm) is
      about 10 times higher than that for transition 4s5s(3)S(1)->4s4p(3)P(2) of Zn I
      (481.1 nm). The appearance and enhancement of the Cu(2) (A-X) band at lower
      ambient pressure and formation of nanoparticle clusters have been extensively
      discussed. Stoichiometric and morphological study of the deposited nanoparticles
      on carbon tape at different ambient pressure reveals a different percentage
      composition of copper and of nanoparticles.

PMID- 22410920
TI  - Fraunhofer-type absorption lines in double-pulse laser-induced plasma.
AB  - We studied the confocal double-pulse laser-induced plasma in the very beginning
      of its life. It was found that the second laser pulse fired 0.7 to 5 us after the
      first pulse produces plasma which, during the first 0 to 20 ns, resembles solar
      configuration. There is a very hot and compact plasma core that radiates a broad
      continuum spectrum and a much larger and cooler outer shell. The light from the
      hot core passes through the cold outer shell and is partly absorbed by atoms and
      ions that are in ground (or close to ground) states. This produces absorption
      lines that are similar to Fraunhofer lines observed in the sun spectrum. The
      possibility to use these absorption lines for new direct and calibration free
      laser-induced breakdown spectroscopy analytical applications, both in laboratory
      and industrial conditions, is proved.

PMID- 22410921
TI  - Correlation of limestone beds using laser-induced breakdown spectroscopy and
      chemometric analysis.
AB  - Correlation of limestone beds is commonly based on a variety of features,
      including the age of the bed, the fossil assemblage, internal sedimentary
      structures, and the relationship to other units in the stratigraphy. This study
      uses laser-induced breakdown spectroscopy (LIBS) to correlate 16 limestone beds
      from Kansas, USA, using three multivariate techniques: (1) soft independent
      modeling of class analogy (SIMCA) classification, (2) a partial least squares
      regression, 1 variable (PLS-1) model in which the spectra are regressed against a
      matrix of the indicator variables 1 through 16, and (3) a matching algorithm that
      consists of a sequence of binary PLS-1 models. Each gravel-sized limestone
      particle was analyzed by one LIBS shot; ten spectra were averaged into a single
      spectrum for chemometric analysis. The entire spectrum (198-969 nm wavelength) is
      used for multivariate analysis; the only preprocessing is averaging. The SIMCA
      and PLS-1 models fail to discriminate among the beds, which are chemically
      similar. In contrast, the matching algorithm has a success rate of 95% to 96%,
      using half of the spectra to train the model and the other half of the spectra to
      validate it. However, 100% success can be accomplished by accepting the
      classification of the majority of spectra for a given bed as the correct
      classification. This study indicates that LIBS can be applied to complex geologic
      correlation problems and provide rapid, accurate results.

PMID- 22410922
TI  - Quantitative carbon measurement in anthracite using laser-induced breakdown
      spectroscopy with binder.
AB  - Quantitative carbon measurement in anthracites remains difficult with laser
      induced breakdown spectroscopy (LIBS) due to its relatively high measurement
      uncertainty. To improve the measurement repeatability, binders to bind the
      anthracite powder together were utilized for LIBS measurement. Results showed
      that the optimized binder Na(2)SiO(3).9H(2)O, with Si from the binder as the
      internal calibration element, can yield the overall best measurement precision
      and accuracy. Using 15 anthracites for calibration and 7 anthracites for
      validation and with optimized percentage of Na(2)SiO(3).9H(2)O as binder, the
      average value of the measurement's relative standard deviation (RSD), R(2), and
      root mean square error of prediction (RMSEP) were 12.1%, 0.76, and 6.25%,
      respectively, proving the applicability of binder for carbon measurement in
      anthracites.

PMID- 22410923
TI  - Toward the optimization of double-pulse LIBS underwater: effects of experimental
      parameters on the reproducibility and dynamics of laser-induced cavitation
      bubble.
AB  - Double-pulse laser-induced breakdown spectroscopy (LIBS) was recently proposed
      for the analysis of underwater samples, since it overcomes the drawbacks of rapid
      plasma quenching and of large continuum emission, typical of single-pulse
      ablation. Despite the attractiveness of the method, this approach suffers
      nevertheless from a poor spectroscopic reproducibility, which is partially due to
      the scarce reproducibility of the cavitation bubble induced by the first laser
      pulse, since pressure and dimensions of the bubble strongly affect plasma
      emission. In this work, we investigated the reproducibility and the dynamics of
      the cavitation bubble induced on a solid target in water, and how they depend on
      pulse duration, energy, and wavelength, as well as on target composition. Results
      are discussed in terms of the effects on the laser ablation process produced by
      the crater formation and by the interaction of the laser pulse with floating
      particles and gas bubbles. This work, preliminary to the optimization of the
      spectroscopic signal, provides an insight of the phenomena occurring during laser
      ablation in water, together with useful information for the choice of the laser
      source to be used in the apparatus.

PMID- 22410924
TI  - Effect of voltage and capacitance in nanosecond pulse discharge enhanced laser
      induced breakdown spectroscopy.
AB  - The laser ablation fast pulse discharge plasma spectroscopy (LA-FPDPS) technique
      has demonstrated its validity to enhance the optical emission of laser-induced
      plasma. It has the potential to improve the performance of traditional LIBS
      measurement. Very recently, LA-FPDPS with a nanosecond pulse discharge circuit
      has been developed, which has a better capability to enhance the optical emission
      intensity of laser plasma compared with that using a microsecond pulse discharge
      circuit. In this paper, the effect of the discharge capacitance and discharge
      voltage on the optical emission of soil plasma generated by LA-FPDPS with a
      nanosecond pulse discharge circuit is evaluated in detail. In addition, the
      stability of the time delay between the laser firing and discharge, and between
      the discharge and optical emission, has been carefully investigated.

PMID- 22410925
TI  - Robust validation of pattern classification methods for laser-induced breakdown
      spectroscopy.
AB  - Laser-induced breakdown spectroscopy (LIBS) is an emerging technology that is
      suitable for a variety of material identification applications. For LIBS to
      successfully transition from the laboratory into field applications, the sensor
      must be paired with the appropriate algorithms for accurate and robust processing
      of the LIBS spectra. In this study we will report on the results of testing
      classification methods on eight distinct classification tasks using LIBS
      datasets. Results suggest that standard cross-validation techniques may not
      accurately estimate generalization performance and a proposed "leave-one-sample
      out" approach to experiment design for classifier validation may provide a more
      robust measure of performance.

PMID- 22410926
TI  - Use of laser-induced breakdown spectroscopy for the differentiation of pathogens
      and viruses on substrates.
AB  - In this work, the use of laser-induced breakdown spectroscopy (LIBS) to
      differentiate live pathogens and killed viruses on substrates is investigated.
      Live pathogens B. anthracis Sterne strain and F. tularensis live vaccine strain
      were interrogated as lawn and colonies on agar; dilutions on agar; and dilutions
      on glass slides, and it was found possible to differentiate among all samples. UV
      killed hantavirusstrains were studied as dilutions on slides and it was also
      found possible to differentiate among strains. To the best of our knowledge, this
      is the first study in which LIBS has been used to differentiate virus samples.

PMID- 22410927
TI  - Advanced signal processing analysis of laser-induced breakdown spectroscopy data
      for the discrimination of obsidian sources.
AB  - Obsidian is a natural glass of volcanic origin and a primary resource used by
      indigenous peoples across North America for making tools. Geochemical studies of
      obsidian enhance understanding of artifact production and procurement and remain
      a priority activity within the archaeological community. Laser-induced breakdown
      spectroscopy (LIBS) is an analytical technique being examined as a means for
      identifying obsidian from different sources on the basis of its 'geochemical
      fingerprint'. This study tested whether two major California obsidian centers
      could be distinguished from other obsidian localities and the extent to which
      subsources could be recognized within each of these centers. LIBS data sets were
      collected in two different spectral bands (350+/-130 nm and 690+/-115 nm) using a
      Nd:YAG 1064 nm laser operated at ~23 mJ, a Czerny-Turner spectrograph with 0.2
      0.3 nm spectral resolution and a high performance imaging charge couple device
      (ICCD) detector. Classification of the samples was performed using partial least
      squares discriminant analysis (PLSDA), a common chemometric technique for
      performing statistical regression on high-dimensional data. Discrimination of
      samples from the Coso Volcanic Field, Bodie Hills, and other major obsidian areas
      in north-central California was possible with an accuracy of greater than 90%
      using either spectral band.

PMID- 22410928
TI  - Multiband sensor using thick holographic gratings for sulfur detection by laser
      induced breakdown spectroscopy.
AB  - Detection of sulfur by optical emission spectroscopy generally presents some
      difficulties because the strongest lines are in the vacuum UV below 185 nm and
      therefore are readily absorbed by oxygen molecules in air. A novel concept for a
      low-cost and efficient system to detect sulfur using near-IR bands by laser
      induced breakdown spectroscopy is here proposed. This concept is based on
      customized thick holographic gratings as spectral filtering elements. The signal
      integration and the temporal synchronization are performed using built-in custom
      electronics that amplify and integrate or trigger photodiode output signals. In
      this work, we use the near-IR lines at 921.287 nm and a background reference at
      900 nm. Preliminary results show a limit of detection comparable to that of a
      conventional high-end system.

PMID- 22410929
TI  - Examining natural rock varnish and weathering rinds with laser-induced breakdown
      spectroscopy for application to ChemCam on Mars.
AB  - A laser-induced breakdown spectroscopy (LIBS) instrument is traveling to Mars as
      part of ChemCam on the Mars Science Laboratory rover. Martian rocks have
      weathered exteriors that obscure their bulk compositions. We examine weathered
      rocks with LIBS in a martian atmosphere to improve interpretations of ChemCam
      rock analyses on Mars. Profile data are analyzed using principal component
      analysis, and coatings and rinds are examined using scanning electron microscopy
      and electron probe microanalysis. Our results show that LIBS is sensitive to
      minor compositional changes with depth and correctly identifies rock type even if
      the series of laser pulses does not penetrate to unweathered material.

PMID- 22410930
TI  - Classification of explosive residues on organic substrates using laser induced
      breakdown spectroscopy.
AB  - Standoff laser induced breakdown spectroscopy (LIBS) has previously been used to
      classify trace residues as either hazardous (explosives, biological, etc.) or
      benign. Correct classification can become more difficult depending on the
      surface/substrate underneath the residue due to variations in the laser-material
      interaction. In addition, classification can become problematic if the substrate
      material has a similar elemental composition to the residue. We have evaluated
      coupling multivariate analysis with standoff LIBS to determine the effectiveness
      of classifying thin explosive residue layers on painted surfaces. Good
      classification results were obtained despite the fact that the painted surface
      contributes to the LIBS emission signal.

PMID- 22410931
TI  - Influence of molybdenum layer on the laser plasma generated from interfacing
      copper layer.
AB  - The results for laser-induced breakdown spectroscopy (LIBS) measurement of thin
      Cu films (1 MUm) on soda-lime glass (SLG) substrates with and without a
      supporting thin Mo layer (1 MUm) are reported. The ablation was carried out using
      a nanosecond Q-switched Nd:YAG laser (lambda=1064 nm, tau=4 ns, spot diameter=50 
      MUm, top-hat profile) in the laser fluence range of 19.16-65.97 J/cm(2). It was
      found that, under the same laser irradiance conditions, the depth and morphology
      of ablation craters produced with and without the Mo layer were completely
      different. The electron number densities of the plasma from the two samples
      calculated from the measured LIBS spectra differed by a factor of 4 as 4.1*10(17)
      cm(-3) (Cu/Mo/SLG) and 17.7*10(17) cm(-3) (Cu/SLG), which was attributed to the
      matrix effects resulting from ionization of Na atoms diffused into the Mo layer.
      It is demonstrated that a nanosecond-laser-based LIBS is applicable for the
      characterization and composition analysis of thin film layers of a few micrometer
      thickness on glass substrates, especially for the measurement of Na contents of
      each layer.

PMID- 22410932
TI  - Pathogen identification with laser-induced breakdown spectroscopy: the effect of
      bacterial and biofluid specimen contamination.
AB  - In this paper, the potential use of laser-induced breakdown spectroscopy (LIBS)
      for the rapid discrimination and identification of bacterial pathogens in
      realistic clinical specimens is investigated. Specifically, the common problem of
      sample contamination was studied by creating mixed samples to investigate the
      effect that the presence of a second contaminant bacterium in the specimen had on
      the LIBS-based identification of the primary pathogen. Two closely related
      bacterial specimens, Escherichia coli strain ATCC 25922 and Enterobacter cloacae
      strain ATCC 13047, were mixed together in mixing fractions of 10:1, 100:1, and
      1000:1. LIBS spectra from the three mixtures were reliably classified as the
      correct E. coli strain with 98.5% accuracy when all the mixtures were withheld
      from the training model and classified against spectra from pure specimens. To
      simulate a rapid test for the presence of urinary tract infection pathogens, LIBS
      spectra were obtained from specimens of Staphylococcus epidermidis obtained from
      distilled water and sterile urine. LIBS spectra from the urine-harvested bacteria
      were classified as S. epidermidis with 100% accuracy when classified using a
      model containing only spectra from other Staphylococci species and with 88.5%
      accuracy when a model containing five genera of bacteria was utilized. Bacterial
      specimens comprising five different genera and 13 classifiable taxonomic groups
      of species and strains were compiled in a library that was tested using external
      validation techniques. The importance of utilizing external validation techniques
      where the library is tested with data withheld from all previous testing and
      training of the model was revealed by comparing the results against "leave-one
      out" cross-validation results. Last, the effect of using sequential models for
      the classification of a single unknown spectrum was investigated by comparing the
      misclassification of two closely related bacteria, E. coli and E. cloacae, when
      the classification was first performed using the five-genus bacterial library and
      then with a smaller model consisting only of E. coli and E. cloacae specimens.
      This result shows the utility of using successively more targeted analyses and
      models that use preliminary classifications from more general models as input.

PMID- 22410933
TI  - The beginnings of Applied Optics.
AB  - A commemorative editorial for the 50th anniversary of Applied Optics describes
      how OSA's second journal was born.

PMID- 22410934
TI  - North American Symposium on Laser Induced Breakdown Spectroscopy (NASLIBS):
      introduction to feature issue.
AB  - This feature issue highlights the topics of the 2011 North American Symposium on
      Laser Induced Breakdown Spectroscopy (NASLIBS). These include LIBS application to
      Security and Forensic, Biomedical and Environmental, Liquid Analysis and
      Fundamentals of LIBS, Instrumentation/Commercialization, Fusion with LIBS, and
      New Frontiers.

PMID- 22410935
TI  - Impact of topical nasal steroid therapy on symptoms of nasal polyposis: a meta
      analysis.
AB  - OBJECTIVES/HYPOTHESIS: Topical steroid therapy is an important strategy in the
      management of chronic rhinosinusitis (CRS) with nasal polyposis. The objective of
      this study was to determine the impact of topical steroid therapy on nasal
      symptoms in patients with nasal polyposis. STUDY DESIGN: Systematic review with
      meta-analysis using standardized methodology. METHODS: Study inclusion criteria
      included: randomized, placebo controlled trials, nasal polyposis, and topical
      steroid therapy. Exclusion criteria included: failure to report at least one
      symptom-based outcome measure, concurrent use of systemic steroids, or mixed CRS
      cohorts (polyp and nonpolyp patients). Quantitative analysis was performed using
      a random effect model. The PRISMA guidelines for meta-analysis reporting were
      followed. RESULTS: A total of 19 studies fulfilled eligibility. Seven studies
      were excluded from the meta-analysis due to significant heterogeneity in outcome
      reporting. A total of 12 studies were combined for quantitative analysis and
      demonstrated a pooled risk ratio of 1.72 (95% confidence interval, 1.41-2.09),
      indicating a significant improvement in nasal symptoms. All three topical steroid
      preparations (fluticasone, mometasone, and budesonide) resulted in symptom
      improvement. All seven studies excluded from the meta-analysis qualitatively
      confirmed the overall findings. CONCLUSIONS: Topical nasal steroid therapy
      improves nasal symptoms in CRS patients with nasal polyposis. Future studies will
      need to evaluate the impact on quality of life, preferably using validated
      disease-specific instruments.

PMID- 22410936
TI  - Increased surface spin stability in gamma-Fe2O3 nanoparticles with a Cu shell.
AB  - gamma-Fe(2)O(3) nanoparticles  were coated with a Cu shell in situ during
      synthesis. An interfacial monolayer of CuO in the Cu-coated gamma-Fe(2)O(3)
      nanoparticles was discovered that stabilized the disordered surface spins of
      gamma-Fe(2)O(3) nanoparticles. Element-specific x-ray absorption spectroscopy at
      the L-edges for Cu and Fe indicated the magnetic moment of the Cu in the shell
      interacted with the gamma-Fe(2)O(3) nanoparticle's surface magnetic moments. This
      exchange interaction between the Fe and Cu at the interface permitted an overall
      Cu moment in CuO (an antiferromagnet typically) that altered the gamma-Fe(2)O(3)
      nanomagnetism. Increasing the Cu shell thickness also increased the total Fe
      magnetism of the nanoparticles.

PMID- 22410937
TI  - Technical note: Shape variability induced by reassembly of human pelvic bones.
AB  - In traditional as well as in geometric morphometric studies, the shape of the
      pelvis is often quantified after the reassembly of the two hip bones and the
      sacrum. However, on dry bones, the morphology of the cartilaginous tissues that
      form the two sacroiliac joints and the pubic symphysis before death remains
      unknown, leading to potential inaccuracies and errors during the reassembly
      process. A protocol was established to investigate the effects of reassembly on
      the quantification of pelvis shape. The shape of fresh pelves obtained after
      dissection, in which the three bones are in an anatomically relevant position,
      was compared with the shape of different reassemblies based on the individual dry
      bones of the same individuals. Our results demonstrated a significant effect of
      the reassembly. Variation in the reassembly process is likely related, first, to
      the complete absence of cartilaginous tissues on dry bones and, second, to the
      morphology of the sacroiliac joint which, in vivo, allows physiological
      movements, resulting in different potential positions of the two sacroiliac
      surfaces relative to one another. However, the artificial variation introduced by
      the reassembly process appears small compared with the biological variation
      between the different individuals.

PMID- 22410940
TI  - High-efficiency single emissive layer white organic light-emitting diodes based
      on solution-processed dendritic host and new orange-emitting iridium complex.
AB  - An extremely high-efficiency solution-processed white organic light-emitting
      diode (WOLED) is successfully developed by simultaneously using an ideal
      dendritic host material and a novel efficient orange phosphorescent iridium
      complex. The optimized device exhibits forward-viewing efficiencies of 70.6 cd A(
      1) , 26.0%, and 47.6 lm W(-1)  at a luminance of 100 cd m(-2) , respectively,
      promising the low-cost solution-processed WOLEDs a bright future as the next
      generation of illumination sources.

PMID- 22410941
TI  - [Cystic kidney diseases].
AB  - Cystic kidney diseases are clinically and genetically heterogeneous. The most
      important entities are autosomal-dominant and autosomal-recessive polycystic
      kidney diseases. The proteins encoded by the involved genes are referred to as
      cystoproteins, which are located predominantly in the primary cilia. Primary
      cilia play an important role in cyst formation. Inherited polycystic kidney
      diseases belong to the increasing number of reported ciliopathies, including
      several syndromic entities. An exact diagnosis is the basis for medical care and
      genetic counselling; thus, the diagnostic algorithm should include clinical,
      ultrasonographic and morphological features of the underlying kidney disease,
      knowledge about further features and family history. Molecular genetic testing
      may contribute important information towards a definite diagnosis.

PMID- 22410942
TI  - [Risk-adapted therapy in acute myeloid leukemia].
AB  - The identification and characterization of an increasing number of chromosomal
      and molecular aberrations has not only increased the understanding of the
      pathogenesis of acute myeloid leukemia but also provides the means for a better
      judgment of prognosis and the direction of therapy. Together with patient
      specific factors like age, co-morbidity, and performance status, an
      individualized risk profile can be used to select the most appropriate
      therapeutic strategy.

PMID- 22410943
TI  - [Genetically determined pancreatic diseases].
AB  - Overall, genetically determined diseases of the pancreas are rare. Recently, it
      was demonstrated that in chronic pancreatitis many patients carry genetic changes
      in associated genes. Aside from chronic pancreatitis, cystic fibrosis is also
      characterized by exocrine insufficiency in many patients. Genetic alterations in
      CFTR can be found in patients suffering from chronic pancreatitis and in patients
      with cystic fibrosis. According to this fact, the analysis of CFTR alterations in
      both disease forms has improved the understanding of underlying pathogenetic
      mechanisms. Shwachman-Diamond and Johanson Blizzard syndrome are rare pancreatic
      disorders, characterized by exocrine pancreatic insufficiency in addition to
      other phenotypic features. As such, due to the early onset of both disease forms,
      diagnosis of cystic fibrosis has to be ruled out in patients with exocrine
      insufficiency, which can be achieved by performing sweat chloride tests. Even
      pancreatic cancer can accumulate in some families and a genetic basis was
      recently demonstrated for some patients. In all mentioned disease entities, a
      genetic analysis of associated genes has become essential for establishing the
      diagnosis. Although genetic knowledge and the finding of genetic alterations in
      different genes has not changed therapy of the mentioned diseases so far, the
      future will tell in which way genetic knowledge can be integrated to change
      modalities of therapy.

PMID- 22410944
TI  - [Non-steroidal anti-inflammatory drugs for patients with hypertension and
      coronary artery disease].

PMID- 22410945
TI  - Serum IGF-I in middle age covaries with reproductive life-history traits in
      British men and women.
AB  - OBJECTIVES: The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis may
      be an important component of individual life-history variation. This study
      examined whether IGF-I levels covary with reproductive life-history traits in a
      long-term British cohort study (the National Child Development Study). METHODS:
      Using data on up to 5,252 individuals (2,431 men and 2,821 women) born in March
      1958, relationships of serum IGF-I at age 45 with pubertal age, time to pregnancy
      (TTP), age at first reproduction (AFR), and lifetime reproductive success (LRS)
      were analyzed using general linear models. RESULTS: IGF-I showed modest non
      linear associations with pubertal age, being low in women who first menstruated,
      and men whose voice broke, in the oldest respective age categories. In women, but
      not men, IGF-I was negatively related to TTP. IGF-I was positively associated
      with AFR in both sexes and tended to be negatively related to LRS in women only.
      Some, but not all, relationships were attenuated after controlling for multiple
      potential confounders. CONCLUSION: These results are consistent with the
      hypothesis that the GH/IGF-I axis partially underlies individual variance in
      reproductive outcomes, through either direct endocrine effects on reproductive
      function or behavior, indirect effects on other traits, or a combination of the
      above. Several limitations of this study include the late age at which blood
      samples were collected and the difficulty of disentangling social and biological
      factors contributing to the traits studied. Am. J. Hum. Biol., 2012. (c) 2012
      Wiley Periodicals, Inc.

PMID- 22410947
TI  - Prolongation of cardiac ventricular repolarization under paliperidone:  how and
      how much?

PMID- 22410948
TI  - A study of air pollution with heavy metals in Athens city and Attica basin using
      evergreen trees as biological indicators.
AB  - Concentrations of five metals (cadmium, chromium, copper, nickel and lead) were
      determined in tree leaves collected from 13 areas of the Attica basin and Athens
      city, Greece. Geographical distribution patterns were investigated, and factors
      affecting toxic element accumulation in trees were discussed. The mean heavy
      metal content in the tree leaves is described in the descending order of
      copper>lead>nickel>chromium>cadmium. Generally, the most damaged areas have been
      proved to be those near the city center and in the vicinity of the Attica
      highway. The geomorphological relief of the area plays an important role in the
      dispersion of airborne particles from pollution sources to the surrounding area.
      Areas on the NE region are also polluted mainly due to wind directions. In Citrus
      aurantium leaves, with relatively impermeable cuticle, high chromium, copper and
      nickel concentration would be possibly caused only by significant stomatal
      uptake. The conifer tree Pinus brutia providing a rough leaf surface also showed
      elevated concentrations, especially of cadmium and lead. The thick waxy cuticle
      of the sclerophyllous broad-leaved Olea europaea forms a smooth sheet increasing
      the barrier properties of the leaf epidermis and causing a reduction in leaf
      permeability. The dense trichomes of the abaxial epidermis of Olea europaea also
      act as a pollution screen keeping away the air particles from the epidermis
      stomata. The presence of a certain metal within the leaf cells could reduce the
      uptake or toxicity of some others.

PMID- 22410949
TI  - Vitamin D supplementation modulates blood and tissue zinc, liver glutathione and
      blood biochemical parameters in diabetic rats on a zinc-deficient diet.
AB  - Previous studies suggest a protective effect of vitamin D3 on zinc deficiency
      induced insulin secretion and on pancreas beta-cell function. The aim of this
      study was to investigate the effect of vitamin D on blood biochemical parameters,
      tissue zinc and liver glutathione in diabetic rats fed a zinc-deficient diet. For
      that purpose, Alloxan-induced diabetic rats were divided into four groups. The
      first group was fed a zinc-sufficient diet while the second group was fed a zinc
      deficient diet. The third and fourth groups received zinc-sufficient or zinc
      deficient diets plus oral vitamin D3 for 27 days. At the end of the experiment,
      blood, femur, pancreas, kidney and liver samples were taken from all rats. The
      serum, femur, pancreas, kidney and liver zinc concentrations, liver glutathione,
      serum alkaline phosphatase activity, daily body weight gain and food intake were
      lower in the zinc-deficient rats in comparison with those receiving adequate
      amounts of zinc. These values were increased in the zinc-deficient group that was
      supplemented with vitamin D3. The serum total cholesterol, triglycerides, total
      protein, urea, glutamate oxaloacetate transaminase, glutamate pyruvate
      transaminase and blood glucose values were higher in rats fed a zinc adequate
      diet, but their concentrations were decreased by vitamin D3 supplementation. The
      serum total protein levels were not changed by zinc deficiency and vitamin D3
      supplementation. These results suggest that vitamin D3 modulates tissue zinc,
      liver glutathione and blood biochemical values in diabetic rats fed a zinc
      deficient diet.

PMID- 22410950
TI  - Finding biomarkers is getting easier.
AB  - Single biomarkers are rarely accurate. Even suites of biomarkers can give
      conflicting results. Ideally potent combinations of variables are isolated which
      accurately identify specific analytes and their level of toxicity. The search for
      such combinations can be done by reducing the thousands of candidate variables to
      the small number necessary for treatment classification. When the key variables
      are recognized by machine learning (ML) the results are quite surprising, given
      the apparent failure of other searching methods to produce good diagnostics.
      Proteins seem especially useful for portable field tests of a variety of adverse
      conditions. This review shows how ML, in particular artificial neural networks,
      can find potent biomarkers embedded in any type of expression data, mainly
      proteins in this article. A computer does multiple iterations to produce sets of
      proteins which systematically identify (to near 100% accuracy) the treatment
      classes of interest. Whether these proteins are useful in actual diagnoses is
      tested by presenting the computer model with unknown classes. Finding the
      biomarkers is getting easier but there still must be confirmation, by
      multivariable statistics and with field studies.

PMID- 22410951
TI  - An approach to detecting estrogenic endocrine disruption via choriogenin
      expression in an estuarine model fish species.
AB  - A large body of work has established a link between endocrine disrupting
      compounds (EDCs) and a number of abnormalities in fishes. However, most EDC
      studies use several standard laboratory denizens to assess impacts, so
      assumptions about sensitivity are primarily based on these few species.
      Additionally, existing methods rely on obtaining sufficient plasma to measure EDC
      biomarkers. Our objectives were (a) to establish a new model species for
      estuarine fishes, (b) to evaluate endocrine impacts with a highly sensitive and
      specific biomarker, and (c) to develop a method for the analysis of this
      biomarker in small fish that do not possess sufficient blood plasma for protein
      measurement. As such, we created a polyclonal antibody (Ab) to the estrogen
      responsive proteins chorion (Ch) and choriogenin (Chg) in Menidia beryllina,
      found throughout coastal North America and already utilized in EPA Whole Effluent
      Testing. We then validated the Ab by using it to measure the response to aqueous
      ethinylestradiol (EE2) through the development an ELISA using Menidia whole body
      homogenate (WBH). Sensitivity of the Ab to Menidia WBH is greater than that of
      the commercially available option. ELISA sensitivity, with a detection limit of 5
      ng/ml and a working range of 22.6-1370.9 ng/ml, is comparable to ELISAs developed
      to measure plasma Chg. To our knowledge this is the first ELISA method developed
      for the detection of Chg using WBH. Including additional model species and
      methods allowing the evaluation of alternative sample matrices will contribute to
      an enhanced understanding of inter-species differences in EDC response.

PMID- 22410952
TI  - A practical strategy for sEMG-based knee joint moment estimation during gait and
      its validation in individuals with cerebral palsy.
AB  - Individuals with cerebral palsy have neurological deficits that may interfere
      with motor function and lead to abnormal walking patterns. It is important to
      know the joint moment generated by the patient's muscles during walking in order
      to assist the suboptimal gait patterns. In this paper, we describe a practical
      strategy for estimating the internal moment of a knee joint from surface
      electromyography (sEMG) and knee joint angle measurements. This strategy requires
      only isokinetic knee flexion and extension tests to obtain a relationship between
      the sEMG and the knee internal moment, and it does not necessitate comprehensive
      laboratory calibration, which typically requires a 3-D motion capture system and
      ground reaction force plates. Four estimation models were considered based on
      different assumptions about the functions of the relevant muscles during the
      isokinetic tests and the stance phase of walking. The performance of the four
      models was evaluated by comparing the estimated moments with the gold standard
      internal moment calculated from inverse dynamics. The results indicate that an
      optimal estimation model can be chosen based on the degree of cocontraction. The
      estimation error of the chosen model is acceptable (normalized root-mean-squared
      error: 0.15-0.29, R: 0.71-0.93) compared to previous studies (Doorenbosch and
      Harlaar, 2003; Doorenbosch and Harlaar, 2004; Doorenbosch, Joosten, and Harlaar,
      2005), and this strategy provides a simple and effective solution for estimating
      knee joint moment from sEMG.

PMID- 22410953
TI  - Real-time control of angioplasty balloon inflation based on feedback from
      intravascular optical coherence tomography: experimental validation on an excised
      heart and a beating heart model.
AB  - We report on real-time control of balloon inflation inside porcine arteries. In
      the first step, experiments were done in a coronary artery of an excised heart.
      In the second step, experiments were done in a beating heart setup providing
      conditions very close to in vivo conditions without the complications. A
      programmable syringe pump was used to inflate a compliant balloon in arteries,
      while intravascular optical coherence tomography (IVOCT) monitoring was
      performed. In a feedback loop, IVOCT images were processed to provide the balloon
      diameter values in real time to control the pump action in order to achieve a
      target diameter. In different experiments, various flow rates and target
      diameters were used. In the excised heart experiment, there was good convergence
      to target diameters resulting in a satisfactory balloon inflation control. In the
      beating heart experiment, there were oscillations in the diameter values due to
      cyclic arterial contractions. In these experiments, the control system maintained
      diameter averages satisfactorily close to predetermined target values. Real-time
      control of balloon inflation could not only provide a safer outcome for
      angioplasty procedures, but could also provide additional information for
      diagnostics since it implicitly provides information about the artery response to
      the inflation process.

PMID- 22410954
TI  - A multiscale model for bioimpedance dispersion of liver tissue.
AB  - Radio-frequency ablation (RFA) has been used in liver surgery to minimize blood
      loss during tissue division. However, the current RFA tissue division method
      lacks an effective way of determining the stoppage of blood flow. There is
      limitation on the current state-of-the-art laser Doppler flow sensor due to its
      small sensing area. A new technique was proposed to use bioimpedance for blood
      flow sensing. This paper discusses a new geometrical multiscale model of the
      liver bioimpedance incorporating blood flow impedance. This model establishes
      correlation between the physical tissue structure and bioimpedance measurement.
      The basic Debye structure within a multilevel framework is used in the model to
      account for bioimpedance dispersion. This dispersion is often explained by the
      Cole-Cole model that includes a constant phase element without physical
      explanation. Our model is able to account for reduced blood flow in its output
      with changes in permittivity in gamma dispersion that is mainly due to the
      polarization of water molecules. This study demonstrates the potential of a
      multiscale model in determining the stoppage of blood flow during surgery.

PMID- 22410955
TI  - Filter-based methodology for the location of hot spots in proteins and exons in
      DNA.
AB  - The so-called receiver operating characteristic technique is used as a tool in an
      optimization procedure for the improvement and assessment of a filter-based
      methodology for the location of hot spots in protein sequences and exons in DNA
      sequences. By optimizing the characteristic values of the nucleotides, high
      efficiency as well as improved accuracy can be achieved relative to results
      obtained with the electron-ion interaction potentials. On the other hand, by
      using the proposed filter-based methodology with binary sequences, improved
      accuracy can be achieved although the efficiency is somewhat compromised relative
      to that achieved using the optimized characteristic values. Extensive
      experimental results, evaluated using measures such as the g-mean, the Matthews
      correlation coefficient, and the chi-square statistic, show that the filter-based
      methodology performs much better than existing techniques using the short-time
      discrete Fourier transform, particularly in applications where short exons are
      involved.

PMID- 22410956
TI  - Radical-mediated nitrile translocation as the key step in the stereoselective
      transformation of 2-(4-chloro-2-cyanobutyl)aziridines to methyl cis-(1-arylmethyl
      4-phenylpiperidin-2-yl)acetates.
AB  - Non-activated 2-(4-chloro-2-cyano-2-phenylbutyl)aziridines were used as building
      blocks for the stereoselective synthesis of novel cis-2-cyanomethyl-4
      phenylpiperidines via a microwave-assisted aziridine to piperidine ring expansion
      followed by a radical-induced nitrile translocation through initial formation and
      subsequent cleavage of intermediate bicyclic iminyl radicals. Furthermore, these
      2-(cyanomethyl)piperidines were shown to be eligible substrates for the
      preparation of methyl cis-(1-arylmethyl-4-piperidin-2-yl)acetates through a
      Pinner reaction using gaseous HCl in methanol.

PMID- 22410957
TI  - Female genital system tuberculosis: a retrospective clinicopathological study of
      1,548 cases in Turkish women.
AB  - PURPOSE: The incidence of tuberculosis (TB) has increased worldwide in the past
      decade and it still remains an important global public health problem. METHOD: A
      retrospective clinicopathological study of 1,548 cases of female genital
      tuberculosis between 1940 and 2011 was conducted. RESULTS: The mean age of the
      cases was 29.49 years. Involvement of the endometrium was noted in 1,073,
      fallopian tubes in 164, cervix in 157, and 154 had multiple organ involvement.
      Clinically, 115 cases (7.4%) were diagnosed as having primary infertility and 12
      cases (0.8%) as having secondary infertility. There was a coexistent carcinoma in
      1.5% of the cases. Peritoneal tuberculosis in 21 cases and tuberculous
      lymphadenitis in 7 cases were seen as well. CONCLUSION: The clinicopathological
      criteria of female genital tuberculosis in the different organs are described,
      and special attention is paid to infertility associated with tuberculous lesion,
      and awareness of the fact that the disease is still with us is thus particularly
      important.

PMID- 22410958
TI  - Cancer during pregnancy: perinatal outcome after in utero exposure to
      chemotherapy.
AB  - OBJECTIVES: To study the outcome of pregnancies complicated by malignant disease,
      in particular neonatal morbidity and mortality after in utero exposure to
      chemotherapy. METHODS: This prospective study included 118 patients diagnosed
      with malignant disease for the first time during pregnancy over an 8-year period
      (March 2003-March 2011). Outcome of neonates born to mothers who received
      chemotherapy during pregnancy was studied and compared with a control group.
      RESULTS: The commonest cancer type diagnosed during pregnancy (56/118 = 47.45 %)
      was breast carcinoma followed by lymphoma/leukemia (32 = 27.12 %). Gynecological
      tumors (all ovarian) represented 10.16 %, soft tissue tumors 5.08 %, colorectal
      4.23 %, thyroid 2.54 % and others 3.38 %. Sixty-one (51.64 %) women received
      chemotherapy (average 3 +/- 2 cycles) during the second and third trimesters. The
      incidence of neonatal survival, preterm birth, small for gestational age and
      congenital malformations was not significantly different between women who
      received chemotherapy during pregnancy and the control group. Five (4.23 %) women
      with advanced disease died during or shortly after termination of pregnancy.
      CONCLUSION: In utero exposure to chemotherapy during the second and third
      trimesters of pregnancy carries minimal morbidity to the unborn fetus.

PMID- 22410959
TI  - Guaianolides and volatile compounds in chamomile tea.
AB  - Chamomile (German Chamomile, Matricaria recutita L., Asteraceae) is one of the
      most popular medicinal plants in use as an herbal tea for food purposes and in
      folk medicine. Qualitative and semi-quantitative analyses of the volatile
      fraction of chamomile herbal tea were performed. Volatile constituents of the
      infusion were isolated by two different methods, namely hydrodistillation and
      solid phase extraction (SPE), and analysed by GC-MS. The relative proportions of
      particular chemical classes, present in the essential oil and volatile fractions
      of the infusion showed remarkable differences. The proportion of mono- and
      sesquiterpene hydrocarbons in the infusion, as compared to the essential oil, was
      significantly lower. Strikingly, the dichloromethane extract of the infusion
      contained a lower amount of bisabolol oxides and chamazulene, but higher amounts
      of spiroethers, sesquiterpene lactones and coumarins, as compared to the
      hydrodistillates of the herbal drug and the infusion. In addition to the
      previously known guaianolides matricarin and achillin, acetoxyachillin and
      leucodin (= desacetoxymatricarin), corresponding C-11 stereoisomers with various
      biological activities typically occurring in Achillea species, were identified in
      the dichloromethane extract of chamomile tea for the first time.

PMID- 22410960
TI  - Scoping review report: obesity in older adults.
AB  - Obesity is associated with an increased risk for early death, heart disease and
      stroke, disability and several other comorbidities. Although there is concern
      about the potential burden on health-care services with the aging demographic and
      the increasing trend of obesity prevalence in older adults, evidence on which to
      base management strategies is conflicting for various reasons. The analytic
      framework for this review is based on a scoping review methodology, and was
      conducted to examine what is known about the diagnosis, treatment and management
      of obesity in older adults. A total of 492 relevant research articles were
      identified using PubMed, Scirus, EBSCO, Clinicaltrials.gov, Cochrane Reviews and
      Google Scholar. The findings of this review indicate that the current WHO (World
      Health Organization)-recommended body mass index, waist circumference and waist
      to-hip ratio obesity thresholds for the general adult population may not be
      appropriate for older adults. Alternatively, weight change or physical fitness
      may be more useful measures of mortality and health risk in obese older adults.
      Furthermore, although obesity in older adults is associated with several
      disorders that increase functional disability, epidemiological evidence suggests
      that obesity is protective against mortality in seniors. Consequently, the trend
      toward increasing prevalence of obesity in older adults will lead to an increase
      in unhealthy life years and health-care costs. The findings from this review also
      suggest that treatment strategies for obese older adults should focus on
      maintaining body weight and improving physical fitness and function rather than
      weight loss, and that a combination of aerobic and resistance exercise appears to
      be the most effective strategy. In conclusion, this review demonstrates the need
      for more research to clarify the definition of obesity in older adults, to
      establish criteria for evaluating when to treat older adults for obesity, and to
      develop effective treatment strategies focused on functional outcomes in obese
      older adults.

PMID- 22410961
TI  - Faecal calprotectin levels before and after weight loss in obese and overweight
      subjects.
AB  - Faecal calprotectin (FCP) is a non-invasive biomarker of intestinal inflammation,
      levels of which are reported to be elevated in individuals with increased body
      mass index (BMI). We investigated whether weight loss (WL), induced by dietary
      and behavioural change in a community weight loss programme (Slimming World), was
      associated with a reduction in FCP in a longitudinal cohort study. We obtained
      paired stool samples at the start and 11-15 weeks into the weight loss programme
      in 40 individuals with a BMI >25 kg m(-2) and no known colorectal or systemic
      inflammatory condition. Eight of 40 (20%) 'healthy' participants had a baseline
      FCP greater than 50 MUg g(-1) (the accepted adult cutoff value for FCP), termed
      FCP(high). Although the degree (%) of WL was similar (5.1 FCP(high) versus 6.1
      FCP(normal); P=0.63), only FCP(high) individuals, but not FCP(normal)
      participants, demonstrated a reduction in FCP level (median 0.3-fold versus 1.0
      fold (that is, no change) during the study period (P=0.065). A large prospective
      cohort study of FCP(high) and FCP(normal) obese individuals is now required to
      determine the relationship between local mucosal inflammation and the systemic
      inflammatory state associated with obesity, as well as understand the
      relationship between FCP levels, WL and future risk of colorectal neoplasia.

PMID- 22410962
TI  - The type and quantity of dietary fat and carbohydrate alter faecal microbiome and
      short-chain fatty acid excretion in a metabolic syndrome 'at-risk' population.
AB  - INTRODUCTION AND OBJECTIVES: An obese-type human microbiota with an increased
      Firmicutes:Bacteroidetes ratio has been described that may link the gut
      microbiome with obesity and metabolic syndrome (MetS) development. Dietary fat
      and carbohydrate are modifiable risk factors that may impact on MetS by altering
      the human microbiome composition. We determined the effect of the amount and type
      of dietary fat and carbohydrate on faecal bacteria and short chain fatty acid
      (SCFA) concentrations in people 'at risk' of MetS. DESIGN: A total of 88 subjects
      at increased MetS risk were fed a high saturated fat diet (HS) for 4 weeks
      (baseline), then randomised onto one of the five experimental diets for 24 weeks:
      HS; high monounsaturated fat (MUFA)/high glycemic index (GI) (HM/HGI); high
      MUFA/low GI (HM/LGI); high carbohydrate (CHO)/high GI (HC/HGI); and high CHO/low
      GI (HC/LGI). Dietary intakes, MetS biomarkers, faecal bacteriology and SCFA
      concentrations were monitored. RESULTS: High MUFA diets did not affect individual
      bacterial population numbers but reduced total bacteria and plasma total and LDL
      cholesterol. The low fat, HC diets increased faecal Bifidobacterium (P=0.005, for
      HC/HGI; P=0.052, for HC/LGI) and reduced fasting glucose and cholesterol compared
      to baseline. HC/HGI also increased faecal Bacteroides (P=0.038), whereas HC/LGI
      and HS increased Faecalibacterium prausnitzii (P=0.022 for HC/HGI and P=0.018,
      for HS). Importantly, changes in faecal Bacteroides numbers correlated inversely
      with body weight (r=-0.64). A total bacteria reduction was observed for high fat
      diets HM/HGI and HM/LGI (P=0.023 and P=0.005, respectively) and HS increased
      faecal SCFA concentrations (P<0.01). CONCLUSION: This study provides new evidence
      from a large-scale dietary intervention study that HC diets, irrespective of GI,
      can modulate human faecal saccharolytic bacteria, including bacteroides and
      bifidobacteria. Conversely, high fat diets reduced bacterial numbers, and in the
      HS diet, increased excretion of SCFA, which may suggest a compensatory mechanism
      to eliminate excess dietary energy.

PMID- 22410963
TI  - A review of late-stage CNS drug candidates for the treatment of obesity.
AB  - Obesity is an important causative factor in morbidity, disability and premature
      death. Increasing levels of obesity will impose enormous health, financial and
      social burdens on worldwide society unless effective interventions are
      implemented. For many obese individuals, diet and behavioural modification need
      to be supplemented by pharmacotherapy. Preclinical research has revealed a
      greater understanding of the complex nature of the hypothalamic regulation of
      food intake and has generated a wide range of new molecular targets for the
      development of drug candidates for obesity treatment. As shown by the clinical
      results that have been obtained with this next generation of therapies, some
      approaches, for example, fixed-dose drug combinations, have already demonstrated
      an ability to deliver levels of efficacy that are not achievable with the current
      antiobesity drug therapies. The regulatory and marketing landscape for
      development, registration and commercialisation of novel centrally acting drugs
      for treatment of obesity and related metabolic disorders has changed
      substantially in recent years. Now a much greater emphasis is placed on
      tolerability and safety, as well as efficacy. In this review we briefly describe
      the therapeutic approaches to tackle obesity that are in late-stage clinical
      development. We then discuss drugs in late-stage development for the treatment of
      obesity and also future directions.

PMID- 22410964
TI  - High tributyltin and imposex levels in the commercial muricid Thais chocolata
      from two Peruvian harbor areas.
AB  - The first appraisal of butyltin (BT) contamination linked with imposex incidence
      in Peruvian coastal areas was performed in the present study. Imposex occurrence
      and BT levels in female bodies were analyzed in the rock snail Thais chocolata
      distributed along 10 sites in areas under the influence of Callao and Chimbote
      Harbors. Imposex levels associated to high tributyltin (TBT) concentrations were
      observed in six of 10 studied sites, and the highest imposex levels were seen in
      gastropods collected near the harbor terminals. Tributyltin concentrations were
      the highest reported for gastropod mollusks (up to 662 ng Sn g(-1)) in recent
      studies. Although TBT-based antifouling paints have been banned globally
      (International Maritime Organization, 2008), the combination of high imposex and
      TBTs level with butyltin degradation index values indicated fresh TBT inputs in
      these Peruvian coastal areas. Thus, the need to implement local regulatory
      strategies related to the use of TBT-free antifouling paints is urgent, as is a
      thorough assessment of the effectiveness of the TBT global ban. Moreover, the
      wide distribution of T. chocolata combined with its capability to elicit imposex
      and bioaccumulate BTs renders this a good sentinel species for TBT contamination
      along the western South American coast.

PMID- 22410965
TI  - Effect of jaw thrust and cricoid pressure maneuvers on glottic visualization
      during GlideScope videolaryngoscopy.
AB  - PURPOSE: During performance of direct laryngoscopy in the difficult-to-visualize
      airway, several maneuvers have the potential to impact glottic visualization,
      including jaw thrust and cricoid pressure. The effect of these maneuvers on
      glottic visualization during videolaryngoscopy has not been studied. We evaluated
      the effect of jaw thrust and cricoid pressure maneuvers on both visualization of
      the glottis and the area of glottic opening visible during GlideScope-aided
      videolaryngoscopy. METHODS: One hundred patients were enrolled in this study.
      After induction of general anesthesia, videolaryngoscopy was followed by jaw
      thrust and cricoid pressure maneuvers performed in random order. Laryngeal
      anatomy was recorded continuously and was saved as digital images following the
      initial laryngoscopy and after each maneuver. Glottis grade [modified Cormack and
      Lehane (C&L)] was recorded, as was the total glottic area. RESULTS: There was
      improvement in glottis grade when utilizing jaw thrust maneuver in comparison to
      GlideScope videolaryngoscopy alone (31% improved, 4% worsened; P < 0.001). There
      was no difference in glottis grade when using the cricoid pressure maneuver in
      comparison with videolaryngoscopy alone (39% improved, 20% worsened; P = 0.19).
      Glottic opening area, however, was greater when utilizing the jaw thrust maneuver
      in comparison with videolaryngoscopy alone (P < 0.001), but smaller when
      utilizing the cricoid pressure maneuver in comparison with videolaryngoscopy
      alone (P < 0.001). CONCLUSIONS: The jaw thrust maneuver was superior to
      videolaryngoscopy alone in improving the modified C&L grade and the visualized
      glottic area; however, no significant improvement was noted with cricoid
      pressure. We therefore recommend the use of jaw thrust as a first-line maneuver
      to aid in glottic visualization and tracheal intubation during GlideScope
      videolaryngoscopy.

PMID- 22410966
TI  - An automated approach for the parameterization of accurate intermolecular force
      fields: pyridine as a case study.
AB  - An automated protocol is proposed and validated, which integrates accurate
      quantum mechanical calculations with classical numerical simulations.
      Intermolecular force fields, (FF) suitable for molecular dynamics (MD) and Monte
      Carlo simulations, are parameterized through a novel iterative approach, fully
      based on quantum mechanical data, which has been automated and coded into the
      PICKY software, here presented. The whole procedure is tested and validated for
      pyridine, whose bulk phase, described through MD simulations performed with the
      specifically parameterized FF, is characterized by computing several of its
      thermodynamic, structural, and transport properties, comparing them with their
      experimental counterparts.

PMID- 22410967
TI  - Structural and static electric response properties of highly symmetric lithiated
      silicon cages: theoretical predictions.
AB  - It is shown by density functional theory calculations that high symmetry silicon
      cages can be designed by coating with Li atoms. The resulting highly symmetric
      lithiated silicon cages (up to D(5d) symmetry) are low-lying true minima of the
      energy hypersurface with binding energies of the order of 4.6 eV per Si atom and
      moderate highest occupied molecular orbital-lowest unoccupied molecular orbital
      gaps. Moreover, relying on a systematic study of the electric response properties
      obtained by ab initio (Hartree-Fock, MP2, and configuration interaction singles
      (CIS)) and density functional (B3LYP, B2PLYP, and CAM-B3LYP) methods, it is shown
      that lithium coating has a large impact on the magnitude of their second
      hyperpolarizabilities resulting to highly hyperpolarizable species. Such
      hyperpolarizable character is directly connected to the increase in the density
      of the low-lying excited states triggered by the interaction between the Si cage
      and the surrounding Li atoms.

PMID- 22410968
TI  - Vibrational averaging of the chemical shift in crystalline alpha-glycine.
AB  - Averaging of the chemical shift over the molecular motion improves the simulated
      data and provides additional information about the temperature dependence and
      system dynamics. However, crystal modeling is difficult due to the limited
      precision of the plane-wave density functional theory (DFT) methods and
      approximate vibrational schemes. On the glycine example, we investigate how the
      averaging can be achieved within the periodic boundary conditions at the DFT
      level. The nuclear motion is modeled with the vibrational configuration
      interaction, with other simplified quantum anharmonic schemes, and the classical
      Born-Oppenheimer molecular dynamics (BOMD). The results confirm a large
      vibrational contribution to the isotropic shielding values. Both the first and
      second derivatives of the shielding were found important for the quantum
      averaging. The first derivatives influence the shielding mostly due to the
      anharmonic character of the CH and NH stretching modes, whereas second
      derivatives produce most vibrational corrections associated with the lower
      frequency vibrational modes. Temperature excitations of the lowest-frequency
      vibrational states and the expansion of the crystal cell both determine the
      temperature dependence of nuclear magnetic resonance parameters. The vibrational
      quantum approach as well as classical BOMD schemes provided temperature
      dependencies of the chemical shifts that are consistent with the previous
      experimental data.

PMID- 22410969
TI  - Hydrogen liberation from the hydrolytic dehydrogenation of dimethylamine-borane
      at room temperature by using a novel ruthenium nanocatalyst.
AB  - Herein we report the discovery of an in situ generated, highly active
      nanocatalyst for the room temperature dehydrogenation of dimethylamine-borane in
      water. The new catalyst system consisting of ruthenium(0) nanoparticles
      stabilized by the hydrogenphosphate anion can readily and reproducibly be formed
      under in situ conditions from the dimethylamine-borane reduction of a
      ruthenium(III) precatalyst in tetrabutylammonium dihydrogenphosphate solution at
      25 +/- 0.1  degrees C. These new water dispersible ruthenium nanoparticles were
      characterized by using a combination of advanced analytical techniques. The
      results show the formation of well-dispersed ruthenium(0) nanoparticles of 2.9 +/
      0.9 nm size stabilized by the hydrogenphosphate anion in aqueous solution. The
      resulting ruthenium(0) nanoparticles act as a highly active catalyst in the
      generation of 3.0 equiv. of H(2) from the hydrolytic dehydrogenation of
      dimethylamine-borane with an initial TOF value of 500 h(-1) at 25 +/- 0.1 
      degrees C. Moreover, they provide exceptional catalytic lifetime (TTO = 11,600)
      in the same reaction at room temperature. The work reported here also includes
      the following results; (i) monitoring the formation kinetics of the in situ
      generated ruthenium nanoparticles, by using the hydrogen generation from the
      hydrolytic dehydrogenation of dimethylamine-borane as a catalytic reporter
      reaction, shows that sigmoidal kinetics of catalyst formation and concomitant
      dehydrogenation fits well to the two-step, slow nucleation and then autocatalytic
      surface growth mechanism, A -> B (rate constant k(1)) and A + B -> 2B (rate
      constant k(2)), in which A is RuCl(3).3H(2)O and B is the growing, catalytically
      active Ru(0)(n) nanoclusters. (ii) Hg(0) poisoning coupled with activity
      measurements after solution infiltration demonstrates that the in situ generated
      ruthenium(0) nanoparticles act as a kinetically competent heterogeneous catalyst
      in hydrogen generation from the hydrolytic dehydrogenation of dimethylamine
      borane. (iii) A compilation of kinetic data depending on the temperature and
      catalyst concentration is used to determine the dependency of reaction rate on
      catalyst concentration and the activation energy of the reaction, respectively.

PMID- 22410971
TI  - Hip joint development in children with type IIb developmental dysplasia.
AB  - PURPOSE: The aim of this study was to analyse the results of treatment of
      sonographically diagnosed type IIb developmental hip dysplasia and to identify
      residual hip dysplasia using clinical and radiological assessment. METHODS: We
      retrospectively reviewed the data of 49 children (59 type IIb and 39 type I hips,
      according to Graf's monographic classification) treated in abduction braces. The
      mean age was 9.1 years (range 4-15) at latest follow-up. RESULTS: According to
      the clinical classification of Mckay in Barrett's modification, all the type I
      and type IIb hips had very good results. No statistical differences were found
      between type I and IIb hips when comparing both measured radiological parameters
      and radiological results according to the Severin classification at latest follow
      up. Using our criteria (two or more radiological parameters were outside of their
      normal range), 12 out of 49 type IIb hips demonstrated persistent dysplasia. Of
      the 12 hips, eight sonograms were normal at the end of treatment and four
      patients failed to normalise. No type I hips demonstrated two or more abnormal
      radiographic parameters at latest follow-up. CONCLUSIONS: Despite obtaining
      normal sonograms at the end of treatment, some children with type IIb dysplasia
      may demonstrate radiographic evidence of persistent hip dysplasia over a longer
      follow-up period. Our results suggest that these children should be monitored
      until skeletal maturity.

PMID- 22410970
TI  - Secular trends in body composition for children and young adults: the Fels
      Longitudinal Study.
AB  - OBJECTIVES: To determine secular trends by birth decade in body mass index (BMI),
      waist circumference/height (W/Ht), percent body fat (PBF), and fat-free mass
      adjusted for height squared (FFM/Ht(2) ) in children and adolescents aged 8-18
      years. METHODS: Serial data were analyzed from 628 boys and 591 girls aged 8-18
      years who participated in the Fels Longitudinal Study. Subjects were stratified
      by birth decade from 1960 to 1999. Means and standard deviations were computed
      for all measurements by birth decade, age, and sex. A repeated-measures analysis
      of variance was used data to ascertain secular trends separately for boys and
      girls. RESULTS: Boys and girls born in the 1990s had significantly higher mean
      BMI, W/Ht, and PBF than did children born in previous decades. Mean FFM/Ht(2) was
      significantly smaller in boys born in the 1990s than boys of the same age born in
      earlier decades. No secular trend was noted in FFM/Ht(2) in girls by decade of
      birth. CONCLUSION: Our analysis of serial data collected over 4 decades confirms
      the secular trend in childhood BMI previously observed in successive cross
      sectional studies. Our analysis discloses significant positive secular trends in
      W/Ht and PBF in both boys and girls and a significant negative secular trend in
      FFM/Ht(2) in boys over the last 4 decades of the 20th century. The secular
      changes presage increases in the prevalence of conditions associated with
      childhood and adolescent obesity-such as hypertension, glucose intolerance, and
      dyslipidemia-that may appear as early as the second decade of life.

PMID- 22410972
TI  - A concise minimum eight year follow-up of proximally porous-coated tapered
      titanium femoral stem in primary total hip arthroplasty.
AB  - PURPOSE: Our goal was to assess clinical and radiographic outcomes using a second
      generation circumferentially proximally porous-coated titanium alloy stem at a
      minimum of eight years of follow-up. METHODS: Ninety-one hips (80 patients) with
      Fibre Metal Taper (FMT, Zimmer Inc, Warsaw, IN, USA) femoral stems implanted
      between May 1998 and April 2002 were followed prospectively and re-evaluated at a
      minimum of eight years postoperatively. The median patient age was 56 (range 34
      78) years, with 40 women and 40 men. Radiographic data and clinical follow-up
      using Harris Hip Score (HHS) and EuroQol (EQ)-5D outcome measures were evaluated.
      RESULTS: Mean follow-up was 9.61 (range 8-12.3) years. At the time of the most
      recent follow-up, the mean HHS was 85.8 (range 46-100) points, mean EQ-5D
      Weighted Health State Index was 0.76 (range 0.05-1.00), and mean EQ-5D Visual
      Analogue Score was 80 (range 24-100). All stems were biologically stable, with
      all hips having osseous ingrowth. One stem was revised due to early
      periprosthetic fracture with stem subsidence. No hip had diaphyseal osteolysis.
      CONCLUSIONS: To our knowledge, the data presented here represent the longest
      clinical follow-up of this second-generation cementless, proximally porous-coated
      femoral stem. The stems were found to perform well clinically and
      radiographically beyond the first five years previously reported in the
      literature. Patients had high levels of satisfaction and function, and osseous
      fixation occurred reliably without evidence of distal osteolysis.

PMID- 22410974
TI  - Regulation of stem cell-based therapies in Canada: current issues and concerns.
AB  - Stem cell therapies offer enormous potential for the treatment of a wide range of
      diseases and conditions. Despite the excitement over such advances, regulators
      are faced with the challenge of determining criteria to ensure stem cells and
      their products are safe and effective for human use. However, stem cell-based
      products and therapies present unique regulatory challenges because standard drug
      development models do not wholly apply given the complexity and diversity of
      these products and therapies. As a result, regulatory requirements are often
      unclear and ambiguous creating unnecessary barriers for research. In order to
      better understand the barriers that might affect Canadian stem cell researchers,
      we sought feedback from stakeholders regarding areas of uncertainty or concern
      about existing regulatory oversight of cell therapies. A selection of Canadian
      researchers and clinicians working in the area of stem cell research were
      interviewed to assess certain key questions: 1) whether current regulatory
      requirements are easily accessible and well understood; 2) whether regulatory
      requirements create important challenges or barriers; and 3) whether there is a
      need for further guidance on the issue. The results of this survey are summarized
      and compared to issues and concerns experienced in other countries, as reported
      in the literature, to identify challenges which may be on the horizon and to
      provide possible solutions for regulatory reform.

PMID- 22410975
TI  - The lower bound on the timing resolution of scintillation detectors.
AB  - The timing performance of scintillation detectors is ultimately limited by photon
      counting statistics. In fact, photon counting statistics form a dominant
      contribution to the overall timing resolution of many state-of-the-art detectors.
      A common approach to investigate this contribution is to calculate the variance
      in the registration times of individual scintillation photons within the
      photosensor. However, in general the single-photon variance is not equal to the
      intrinsic limit on the timing resolution, since in principle one can make use of
      the timing information carried by all photons detected. In this work, the Cramer
      Rao lower bound on the timing resolution of a scintillation detector, based on
      the information contained in the full set of registered photons, is calculated.
      The results appear to be in good agreement with trends observed in the
      literature. Furthermore, it is shown that the timestamp obtained from any single
      scintillation photon never yields the optimum timing resolution for realistic
      scintillation detectors. Yet, it appears that the intrinsic timing resolution
      limit can be approached closely by making use of the timestamps from a relatively
      small number of photons emitted during the initial part of the scintillation
      pulse.

PMID- 22410976
TI  - Magnetic field sensing based on V-shaped groove filled with magnetic fluids.
AB  - A magnetic field sensing system based on V-shaped groove filled with magnetic
      fluids is developed in this work. The propagation direction of the emergent light
      after the V-shaped groove (or the position of the emergent light on the detecting
      plane) is related to the strength of the externally applied magnetic field. The
      analytical expressions for the sensing system are derived in detail. The
      sensitivity and other sensing properties of the sensing system are investigated
      numerically and experimentally. The sensing mechanism is analyzed and ascribed to
      the magnetically tunable refractive index of magnetic fluids.

PMID- 22410977
TI  - Highly nonlinear all-solid photonic crystal fibers with low dispersion slope.
AB  - A fluorine-doped trench-assisted structure is proposed to improve the
      nonlinearity of photonic crystal fibers (PCFs). Three all-solid highly nonlinear
      PCFs with low dispersion slope and low confinement loss are designed. They
      exhibit all normal dispersion, two zero dispersion wavelengths (ZDWs) and one ZDW
      just at 1.55 MUm, respectively. The lowest dispersion slope is 5.12*10(-4)
      ps/(km.nm(2)), which is 2 orders of magnitude lower than that of conventional
      highly nonlinear fibers. A nonlinear coefficient of 31.5 W(-1).km(-1) and low
      loss of 9.62*10(-5) dB/km at 1.55 MUm has been achieved for this PCF.

PMID- 22410978
TI  - Photonic generation of tunable microwave signal using Brillouin fiber laser.
AB  - A simple approach to generate two bands of tunable microwave signal is proposed
      and demonstrated. In this scheme, two single-mode fibers with optimized Brillouin
      frequency shift spacing have been chosen as the scattering medium in two cascaded
      ring cavities. Two bands of tunable microwave signal from 390 to 453 MHz and
      10.863 to 11.076 GHz can be obtained through adjusting the temperature of the
      fiber and the pump wavelength. The tunable frequency range can be further
      expanded by using a temperature controller with a wider adjustment range. The
      generated microwave signal exhibits high stability on frequency.

PMID- 22410979
TI  - Microbubble based fiber-optic Fabry-Perot interferometer formed by fusion
      splicing single-mode fibers for strain measurement.
AB  - We demonstrate an all-fiber optical Fabry-Perot interferometer (FPI) strain
      sensor whose cavity is a microscopic air bubble. The bubble is formed by fusion
      splicing together two sections of single-mode fibers (SMFs) with cleaved flat tip
      and arc fusion induced hemispherical tip, respectively. The fabricated
      interferometers are with bubble diameters of typically ~100 MUm. Strain and
      temperature sensitivities of fabricated interferometers are studied
      experimentally; a strain sensitivity of over 4 Pm/MUepsilon and a thermal
      sensitivity of less than 0.9 Pm/ degrees C is obtained.

PMID- 22410980
TI  - Spatial mismatch calibration using circular carrier technique in the simultaneous
      phase shifting interferometry.
AB  - In most simultaneous phase shifting interferometry (SPSI) systems, a group of
      phase shifting interferograms are captured simultaneously at the different
      physical locations to retrieve the phase. The data of different interferograms
      should be spatially matched correctly, which is hard to realize by existing
      methods or this spatial mismatch will lead to phase retrieving error. In this
      paper, a spatial mismatch calibration method is proposed, where the circular
      carrier is introduced in the interferograms of the SPSI system, and the
      modulating phases of any two interferograms can be retrieved by the demodulation
      technique of circular carrier interferogram. The slope of the difference between
      these two phases is proportional to the mismatch value, so this error can be
      extracted and the experiment setup calibrated. The main error sources of the
      proposed method are analyzed with the conclusion that its match precision can be
      achieved up to 0.5 pixel. In addition, the simulated interferograms and actual
      interferograms captured in a SPSI system are processed to validate our proposed
      method.

PMID- 22410981
TI  - Three-dimensional phase step profilometry with a multicore optical fiber.
AB  - This paper demonstrates the feasibility of using phase stepping and a multicore
      optical fiber to calculate an object's depth profile. An interference pattern is
      projected by an optical fiber onto the object. The distorted interference pattern
      containing the object information is captured by a CCD camera and processed using
      a phase step interferometry method. The phase step method is less computationally
      intensive compared to two-dimensional Fourier transform profilometry and provides
      more accuracy when measuring objects of high frequency spatial variations.

PMID- 22410982
TI  - Compact infrared cryogenic wafer-level camera: design and experimental
      validation.
AB  - We present a compact infrared cryogenic multichannel camera with a wide field of
      view equal to 120 degrees . By merging the optics with the detector, the concept
      is compatible with both cryogenic constraints and wafer-level fabrication. The
      design strategy of such a camera is described, as well as its fabrication and
      integration process. Its characterization has been carried out in terms of the
      modulation transfer function and the noise equivalent temperature difference
      (NETD). The optical system is limited by the diffraction. By cooling the optics,
      we achieve a very low NETD equal to 15 mK compared with traditional infrared
      cameras. A postprocessing algorithm that aims at reconstructing a well-sampled
      image from the set of undersampled raw subimages produced by the camera is
      proposed and validated on experimental images.

PMID- 22410983
TI  - Multiparameter measurement of absorbing liquid by time-resolved photoacoustics.
AB  - Measuring constituent concentrations of processing liquids provides highly useful
      data for industrial process control. Techniques that allow online measurement
      will greatly save resources and energy, making them highly attractive for
      enterprises. In this paper, we develop a technique based on time-resolved
      photoacoustics for simultaneously measuring the optical absorption coefficient,
      acoustic speed, and thermal-acoustic transformation coefficient of an absorbing
      liquid, using an experimental setup that merely employs a nanosecond pulsed laser
      with millijoule energy and a single piezoelectric transducer with a wide
      frequency bandwidth. As investigated samples, we use potassium chromate, glucose,
      and their mixing solutions. Experimental results show that the value of each
      parameter measured in a mixed solution is approximately equal to the sum value of
      the same parameter in the constituent solutions. This means that a simultaneous
      measurement of these parameters enables us to calculate two or three constituent
      concentrations in a mixed liquid, if the constituent substances differ clearly
      from one another in terms of their optical absorption, acoustic speed, or thermal
      acoustic transformation properties.

PMID- 22410984
TI  - All-fiber Q-switched operation of thulium-doped silica fiber laser by
      piezoelectric microbending.
AB  - We demonstrate an all-fiber Q-switched laser operation in the 2 um region on the
      basis of a dynamic periodic microbend and pulsed-pump configuration. A single
      mode thulium-doped silica fiber is pumped by 1.6 um-band laser diodes, and the
      dynamic loss is introduced in the fiber ring resonator by the periodic microbend
      that is electrically controlled with a piezoelectric actuator. When the voltage
      off period of the piezoelectric actuator is set at 20 us for the pump power of
      120 mW, the output pulse power is measured by 420 mW with a pulse width of 1.3
      us.

PMID- 22410985
TI  - All-fiber broadband supercontinuum source with high efficiency in a step-index
      high nonlinear silica fiber.
AB  - We demonstrate an all-fiber broadband supercontinuum (SC) source with high
      efficiency in a step-index high nonlinear silica fiber, which was pumped by a
      1557 nm subpicosecond-pulse laser in the normal dispersion region. The broad SC
      spectrum covers the spectral range from 840 to 2390 nm, and the 10 dB bandwidth
      from 1120 nm to 2245 nm of the SC covers one octave, assuming the peaks near 1550
      nm were filtered. The SC source system is constructed by all-fiber components,
      which can be fusion-spliced together directly with low loss, less than 0.1 dB.
      Thus the SC source has high energy transfer efficiency from the pump source. The
      maximum SC average power of 332 mW is obtained, including the peaks near 1550 nm.
      The spectral density for the 10 dB bandwidth is in the range from -17.3 to -7.3
      dBm/nm.

PMID- 22410986
TI  - Generation of midfield concentrated beam arrays using periodic metal annular
      apertures.
AB  - Generation of minimally diffracting beam arrays in the midfield region using
      periodic metal annular apertures is investigated. The relations between the
      patterns of the diffraction fields and the structural parameters of the periodic
      metal annular aperture are numerically analyzed. Material dependent transmission
      characteristics are also studied with finite difference time-domain simulation.
      The results reveal that the beam concentration efficiency and axial intensity
      uniformity have a trade-off restriction due to strong inter-aperture interference
      and surface plasmon mediates the transmission efficiency of the periodic annular
      apertures. The design criteria of the metal annular aperture to achieve the
      strong and uniform beam arrays are addressed.

PMID- 22410987
TI  - Reactive self-tracking solar concentrators: concept, design, and initial
      materials characterization.
AB  - Etendue limits angular acceptance of high-concentration photovoltaic systems and
      imposes precise two-axis mechanical tracking. We show how a planar micro-optic
      solar concentrator incorporating a waveguide cladding with a nonlinear optical
      response to sunlight can reduce mechanical tracking requirements. Optical system
      designs quantify the required response: a large, slow, and localized increase in
      index of refraction. We describe one candidate materials system: a suspension of
      high-index particles in a low-index fluid combined with a localized space-charge
      field to increase particle density and average index. Preliminary experiments
      demonstrate an index change of aqueous polystyrene nanoparticles in response to a
      low voltage signal and imply larger responses with optimized nanofluidic
      materials.

PMID- 22410988
TI  - Measurement of in-plane displacement by wavelength-modulated heterodyne speckle
      interferometry.
AB  - The use of wavelength-modulated light incorporated into an optical-path
      difference speckle interferometer is demonstrated as a heterodyne technique for
      measuring the in-plane displacement of a rough object. The in-plane displacement
      can be determined from the measured phase variation of the heterodyne speckle
      signal. We also improved the optical configuration to create a high-contrast
      interference pattern. Experimental results reveal that the proposed method can
      detect displacement up to a long range of 220 MUm and displacement variation down
      to the nanometer range. Moreover, the sensitivity can reach up to 0.8 degrees
      /nm. The performance of the system is discussed.

PMID- 22410989
TI  - Resonance shifts of transverse-electric whispering gallery modes in a spheroidal
      resonator.
AB  - A variational method was applied to find the wave function of a transverse
      electric whispering gallery mode (WGM) in a spheroidal resonator of a uniform
      refractive index (RI). It was found that the electric field is tangential to the
      resonator surface as in the sphere, up to the linear order of the ellipticity.
      Using the wave function, the resonance shift due to adsorption of a thin, uniform
      dielectric layer onto the surface and the shift by a uniform RI change in the
      surroundings were evaluated in the perturbation theory. The shift by the RI
      change is not affected by the ellipticity, but the shift by the layer adsorption
      now depends on the meridional order. However, the correction is not large unless
      the ellipticity is large and the meridional order is away from the one for the
      equatorial mode of WGM.

PMID- 22410990
TI  - Broadband and mid-infrared absorber based on dielectric-thin metal film
      multilayers.
AB  - We propose a periodic multilayer structure of dielectric and metal interlayers to
      achieve a near-perfect broadband absorber of mid-infrared radiation. We examine
      the influence of four factors on its performance: (1) the interlayer metal
      conductance, (2) the number of dielectric layers, (3) a nanopatterned
      antireflective layer, and (4) a reflective metallic bottom layer for
      backreflection. Absorption characteristics greater than 99% of the 300 K and 500
      K blackbody spectra are found for the optimized structures. Incident angle and
      polarization dependence of the absorption spectra are examined. We also
      investigate the possibility of fabricating a nanopatterned antireflective layer
      to maximize absorption.

PMID- 22410991
TI  - Temperature-dependent photoluminescence spectra of Er-Tm codoped calcium
      boroaluminate glasses.
AB  - The temperature dependence of photoluminescence (PL) spectra of Er-Tm codoped
      calcium boroaluminate (CABAL) glasses with different dopant concentrations was
      investigated under 15-298 K, by pumping at 795 nm. The intensities of three band
      emissions located at 1.46, 1.53, and 1.80 MUm decreased monotonically when
      increasing the temperature from at lower concentrations. However, the emissions
      peaked at 1.80 MUm increase with the increasing temperature at higher
      concentrations. This was attributed to the increasing of cross relaxation (CR)
      resulting from the high doping concentration of Tm ions. This was evidenced by
      the much shorter fluorescence lifetime of 56 MUs for the 3F4 emission due to 3F4
      >3H6 transition for the CABAL glass codoped with 2.00 mol.% Tm2O3, in comparison
      with 185 MUs for that of 0.2 mol.% Tm2O3. The energy transfer (ET) and CR
      processes between Er3+ and Tm3+ ions have been discussed at different doping
      concentrations and operating temperatures. The nonexponential character of the
      decays of 4I(13/2) and 3H4 with the increasing concentration indicated the
      occurring of a dipole-dipole quenching processes in the framework of a diffusion
      limited regime. The average critical distances of CR between Tm3+ ions and ET
      between Er3+ and Tm3+ ions were approximately 1 nm.

PMID- 22410992
TI  - Semiellipsoid microlens fabrication method using UV proximity printing.
AB  - We present a new semiellipsoid microlens fabrication method that controls the
      printing gap in the UV lithography process without thermal reflow. The UV
      proximity printing method can precisely control the curvature radius ratio of the
      semiellipsoid microlens in the fabrication process. The proposed fabrication
      method facilitates mass production to achieve a high-yield and high-coupling
      semiellipsoid microlens that is suitable to be used in commercial fiber
      transmission systems. A semiellipsoid microlens can be tipped on a single-mode
      fiber end to improve power coupling efficiency from laser diodes. The
      semiellipsoid microlens allows increasing the fiber spot size and numerical
      aperture. It is very important to control the geometric parameters in the
      assembly procedure to increase the optical coupling efficiency between the laser
      diode and single-mode fiber. Wide misalignment tolerance, low loss, and low
      manufacturing cost could be achieved by the proposed fabrication method. The
      theoretical model is first developed to predict the optical coupling efficiency
      for various microstructure geometries of semiellipsoid microlens and assembly
      parameters in this study. Then, the Taguchi method is applied to obtain the
      optimal geometric parameters setting. The results show that optical coupling
      efficiency could be significantly improved by using the optimal geometric
      parameters setting.

PMID- 22410993
TI  - Optical properties of solution-processable semiconducting TiOx thin films for
      solar cell and other applications.
AB  - The optical properties of solution-processable semiconducting titanium suboxide
      (TiOx) thin films were investigated as a function of wavelength (350-800 nm)
      using ellipsometric and optical reflection technique. The variation of refractive
      index under different thermal annealing conditions (room temperature to 900 
      degrees C) was studied. The increase in refractive index with high-temperature
      thermal annealing process was observed, allowing the opportunity to obtain
      refractive index values from 1.77 to 2.57 at a wavelength of 600 nm. The x-ray
      diffraction and atomic force microscopy studies indicate that the index variation
      is due to the TiOx phase, density, and morphology changes under thermal
      annealing. The TiOx thin films have applications in organic and inorganic solar
      cells as well as other optical and photonic devices. We show that TiOx thin films
      can be used as an effective antireflection layer for Si solar cells.

PMID- 22410994
TI  - Extended ABCD matrix formalism for the description of femtosecond diffraction
      patterns; application to femtosecond digital in-line holography with anamorphic
      optical systems.
AB  - We present a new model to predict diffraction patterns of femtosecond pulses
      through complex optical systems. The model is based on the extension of an ABCD
      matrix formalism combined with generalized Huygens-Fresnel transforms (already
      used in the CW regime) to the femtosecond regime. The model is tested to describe
      femtosecond digital in-line holography experiments realized in situ through a
      cylindrical Plexiglas pipe. The model allows us to establish analytical relations
      that link the holographic reconstruction process to the experimental parameters
      of the pipe and of the incident beam itself. Simulations and experimental results
      are in good concordance. Femtosecond digital in-line holography is shown to allow
      significant coherent noise reduction, and this model will be particularly
      efficient to describe a wide range of optical geometries. More generally, the
      model developed can be easily used in any experiment where the knowledge of the
      precise evolution of femtosecond transverse patterns is required.

PMID- 22410995
TI  - Improved algorithm for phase-to-height mapping in phase measuring profilometry.
AB  - An improved algorithm for phase-to-height mapping in phase-measuring profilometry
      (PMP) is proposed, in which the phase-to-height mapping relationship is no longer
      restricted to the condition that the optical axes of the imaging system must be
      orthogonal to the reference plane in the basic PMP. Only seven coefficients
      independent of the coordinate system need to be calibrated, and the system
      calibration can be accomplished using only two different gauge blocks, instead of
      more than three different standard planes. With the proposed algorithm, both the
      phase measurement and system calibration can be completed simultaneously, which
      makes the three-dimensional (3-D) measurement faster and more flexible.
      Experiments have verified its feasibility and validity.

PMID- 22410996
TI  - Photothermal self-phase-modulation technique for absorption measurements on high
      reflective coatings.
AB  - We propose and demonstrate a new measurement technique for the optical absorption
      of high-reflection coatings. Our technique is based on photothermal self-phase
      modulation and exploits the deformation of cavity Airy peaks that occurs due to
      coating absorption of intracavity light. The mirror whose coating is under
      investigation needs to be the input mirror of a high-finesse cavity. Our example
      measurements were performed on a high-reflection SiO2-Ta2O5 coating in a three
      mirror ring-cavity setup at a wavelength of 1064 nm. The optical absorption of
      the coating was determined to be alpha=(23.9+/-2.0).10(-6) per coating. Our
      result is in excellent agreement with an independently performed laser
      calorimetry measurement that gave a value of alpha=(24.4+/-3.2).10(-6) per
      coating. Since the self-phase modulation in our coating-absorption measurement
      affects mainly the propagation through the cavity input mirror, our measurement
      result is practically uninfluenced by the optical absorption of the other cavity
      mirrors.

PMID- 22410997
TI  - Three-dimensional measuring technique for surface topography using a light
      sectioning microscope.
AB  - Three-dimensional (3D) surface topographic analysis, measurement, and assessment
      techniques have raised great interest not only among researchers but also among
      industrial users. Many industrial processes and applications are directly
      influenced by the small-scale roughness of surface finishes. This paper describes
      the development and implementation of a noncontact, three-dimensional,
      microtopography measuring system. The instrument is formed by combining a
      modified light-sectioning microscope subsystem with a computer subsystem. In
      particular, optical system characteristics of the light-sectioning microscope are
      investigated, and a textured steel sheet is measured to demonstrate good
      practical outcomes. Details of measuring processes and image processing
      algorithms are provided, such as procedures for measurement, image edge
      extraction, and 3D topography reconstruction. After the 3D topography of the
      measured surface has been reconstructed, the topography field description
      parameters are calculated. A standard roughness block was used for calibration of
      the surface microtopography measuring system. Results obtained showed the
      measurement method output has good agreement with the actual asperity (unevenness
      or roughness) of the surface. The computer subsystem is used to process and
      control asperity measurements and image generation, and for image acquisition and
      presentation.

PMID- 22410998
TI  - Utilization of a digital-versatile-disc pickup head for benchtop laser
      microfabrication.
AB  - Laser microfabrication is now offering interesting solutions to rapidly produce
      high-resolution photomasks or microstructures. However, most works require
      expensive commercial lasers and computer numerical control platforms, limiting
      its use by a large public. In this paper, we report the construction of a simple,
      custom-made, easily reproducible, automated laser system, based on a DVD optical
      pickup head. A user-friendly computer interface specifically designed to operate
      a motorized three-axis platform with micrometric precision controls focus
      distance and in-plane displacements. Writing performance characterization for
      both direct ablation and sintering of commercial black toner demonstrated
      flexibility in tridimensional microfabrication resolution and speed thanks to
      precise management of laser power and exposure time, with a minimal resolution of
      3.1 MUm.

PMID- 22410999
TI  - On the influence of noise statistics on polarimetric contrast optimization.
AB  - In active scalar polarimetric imaging systems, the illumination and analysis
      polarization states are degrees of freedom that can be used to maximize the
      performance. These optimal states depend on the statistics of the noise that
      perturbs image acquisition. We investigate the problem of optimization of
      discrimination ability (contrast) of such imagers in the presence of three
      different types of noise statistics frequently encountered in optical images
      (Gaussian, Poisson, and Gamma). To compare these different situations within a
      common theoretical framework, we use the Bhattacharyya distance and the Fisher
      ratio as measures of contrast. We show that the optimal states depend on a trade
      off between the target/background intensity difference and the average intensity
      in the acquired image, and that this trade-off depends on the noise statistics.
      On a few examples, we show that the gain in contrast obtained by implementing the
      states adapted to the noise statistics actually present in the image can be
      significant.

PMID- 22411000
TI  - Effect of undernutrition on deciduous tooth emergence among Rajput children of
      Shimla District of Himachal Pradesh, India.
AB  - This article examines the influence of nutritional status on the emergence of
      deciduous dentition in a cross-sectional sample of 510 rural Rajput children from
      the Jubbal and Kotkhai Tehsils, Shimla District, Himachal Pradesh, India. The
      nutritional status of each child was evaluated using Z-scores of height/supine
      length-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ). The
      effects of sex and side on deciduous dental emergence were not statistically
      significant. Partial correlation indicates that the number of emerged teeth (T)
      was more strongly correlated with height than with other anthropometric
      variables. In most age groups, the stunted boys and girls (HAZ <-2) had fewer
      emerged teeth than nonstunted age peers (HAZ >-2). The mean T in underweight
      children was also less than that of the normal children, with a few exceptions.
      The stunted children have a significantly greater likelihood of delayed emergence
      of deciduous dentition. Measures of linear growth status are more closely related
      to dental development than measures of growth in mass. The findings indicate that
      even moderate undernutrition can delay deciduous tooth emergence.

PMID- 22411001
TI  - Against all odds: surviving rhino-orbital-cerebral mucormycosis: a case report.

PMID- 22411003
TI  - Selective oxidation of unactivated C-H bonds by supramolecular control.
AB  - Efficient methods for dioxirane-based selective C-H bond oxidation by
      supramolecular control in H(2)O have been developed. With beta-cyclodextrin as
      the supramolecular host, site-selective oxidation of the terminal over the
      internal tertiary C-H bond of 3,7-dimethyloctyl esters 3a-c was achieved. In
      addition, beta-cyclodextrin selectively enhanced the C-H bond oxidation of cumene
      in a mixture of cumene and ethyl benzene in H(2)O. Through (1)H NMR studies, the
      selectivity in C-H bond oxidation could be attributed to the inclusion complex
      formation between beta-cyclodextrin and the substrates.

PMID- 22411002
TI  - An initial screening for HIV-associated neurocognitive disorders of HIV-1
      infected patients in China.
AB  - HIV-associated neurocognitive disorders (HAND), characterized by cognitive,
      motor, and behavioral abnormalities, are common among people living with HIV and
      AIDS. In combined antiretroviral therapy era in Western countries, nearly 40% of
      HIV-infected patients continue to suffer from HAND, mainly with mild or
      asymptomatic cognitive impairment. However, the prevalence and the clinical
      features of HAND in China are still not well known. In this study, a multi-center
      cross-sectional study was performed to determine the prevalence and clinical
      features of HAND in 134 HIV-1 infected patients in China. The International HIV
      Dementia Scale and a neuropsychological test battery were administered for
      screening and diagnosis HAND. Subjective complaints, CD4 count and viral loads in
      both blood plasma and cerebrospinal fluid were correlated with diagnosis of HAND.
      The results showed that the prevalence of HAND was approximately 37% in these
      patients. CD4 counts at time of sampling were significant lower in the HAND group
      than in the non-HAND group. But the distribution of the HAND severity did not
      differ by CD4 count or viral load. The presence of HAND was associated with
      cognitive and behavior disorder complaints (4.9- and 4.1-fold higher than those
      without HAND, respectively). The present data suggest that CD4 count and viral
      load cannot predict the severity of HAND, although the prevalence of HAND is
      similar to previous report in these patients. Cognitive and behavioral disorder
      is major complaint rather than cognitive and motor impairment. A larger
      prospective study is needed to obtain better estimates of HAND in China.

PMID- 22411004
TI  - Controlled hierarchical architecture in surface-initiated zwitterionic polymer
      brushes with structurally regulated functionalities.
AB  - Hierarchical polymer films with structurally regulated functionalities are
      achieved by integrating 2D and 3D structures to enable ultralow nonspecific
      protein binding and high loading of molecular recognition elements, such as
      antibodies.

PMID- 22411005
TI  - Image super-resolution with sparse neighbor embedding.
AB  - Until now, neighbor-embedding-based (NE) algorithms for super-resolution (SR)
      have carried out two independent processes to synthesize high-resolution (HR)
      image patches. In the first process, neighbor search is performed using the
      Euclidean distance metric, and in the second process, the optimal weights are
      determined by solving a constrained least squares problem. However, the separate
      processes are not optimal. In this paper, we propose a sparse neighbor selection
      scheme for SR reconstruction. We first predetermine a larger number of neighbors
      as potential candidates and develop an extended Robust-SL0 algorithm to
      simultaneously find the neighbors and to solve the reconstruction weights.
      Recognizing that the k-nearest neighbor (k-NN) for reconstruction should have
      similar local geometric structures based on clustering, we employ a local
      statistical feature, namely histograms of oriented gradients (HoG) of low
      resolution (LR) image patches, to perform such clustering. By conveying local
      structural information of HoG in the synthesis stage, the k-NN of each LR input
      patch is adaptively chosen from their associated subset, which significantly
      improves the speed of synthesizing the HR image while preserving the quality of
      reconstruction. Experimental results suggest that the proposed method can achieve
      competitive SR quality compared with other state-of-the-art baselines.

PMID- 22411006
TI  - Nature, nurture or nutrition? Impact of maternal nutrition on maternal care,
      offspring development and reproductive function.
AB  - We have previously reported that offspring of mothers fed a high fat (HF) diet
      during pregnancy and lactation enter puberty early and are hyperleptinaemic,
      hyperinsulinaemic and obese as adults. Poor maternal care and bonding can also
      impact offspring development and disease risk.We therefore hypothesized that
      prenatal nutrition would affect maternal care and that an interaction may exist
      between a maternal HF diet and maternal care, subsequently impacting on offspring
      phenotype.Wistar rats were mated and randomized to control dams fed a control
      diet (CON) or dams fed a HF diet from conception until the end of lactation (HF).
      Maternal care was assessed by observing maternal licking and grooming of pups
      between postnatal day (P)3 and P8. Postweaning (P22), offspring were fed a
      control (-con) or HF (-hf) diet. From P27, pubertal onset was assessed. At ~P105
      oestrous cyclicity was investigated. Maternal HF diet reduced maternal care; HF
      fed mothers licked and groomed pups less than CON dams.Maternal fat:lean ratio
      was higher in HF dams at weaning and was associated with higher maternal plasma
      leptin and insulin concentrations, but there was no effect of maternal care on
      fat:lean ratio or maternal hormone levels. Both female and male offspring of HF
      dams were lighter from birth to P11 than offspring of CON dams, but by P19, HF
      offspring were heavier than controls. Prepubertal retroperitoneal fat mass was
      greater in pups from HF-fed dams compared to CON and was associated with elevated
      circulating leptin concentrations in females only, but there was neither an
      effect of maternal care, nor an interaction between maternal diet and care on
      prepubertal fat mass. Pups from HF-fed dams went into puberty early and this
      effect was exacerbated by a postweaning HF diet.Maternal and postweaning HF diets
      independently altered oestrous cyclicity in females: female offspring of HF-fed
      mothers were more likely to have prolonged or persistent oestrus, whilst female
      offspring fed a HF diet postweaning were more likely to have irregular oestrous
      cycles and were more likely to have prolonged or persistent oestrus. These data
      indicate that maternal HF nutrition during pregnancy and lactation results in a
      maternal obese phenotype and has significant impact on maternal care during
      lactation. Maternal and postweaning nutritional signals, independent of maternal
      care, alter offspring body fat pre-puberty and female reproductive function in
      adulthood, which may be associated with advanced ovarian ageing and altered
      fertility.

PMID- 22411007
TI  - Activation of glutamate transport evokes rapid glutamine release from
      perisynaptic astrocytes.
AB  - Stimulation of astrocytes by neuronal activity and the subsequent release of
      neuromodulators is thought to be an important regulator of synaptic
      communication. In this study we show that astrocytes juxtaposed to the
      glutamatergic calyx of Held synapse in the rat medial nucleus of the trapezoid
      body (MNTB) are stimulated by the activation of glutamate transporters and
      consequently release glutamine on a very rapid timescale. MNTB principal neurones
      express electrogenic system A glutamine transporters, and were exploited as
      glutamine sensors in this study. By simultaneous whole-cell voltage clamping
      astrocytes and neighbouring MNTB neurones in brainstem slices, we show that
      application of the excitatory amino acid transporter (EAAT) substrate d-aspartate
      stimulates astrocytes to rapidly release glutamine, which is detected by nearby
      MNTB neurones. This release is significantly reduced by the toxins L-methionine
      sulfoximine and fluoroacetate, which reduce glutamine concentrations specifically
      in glial cells. Similarly, glutamine release was also inhibited by localised
      inactivation of EAATs in individual astrocytes, using internal DL-threo-beta
      benzyloxyaspartic acid (TBOA) or dissipating the driving force by modifying the
      patch-pipette solution. These results demonstrate that astrocytes adjacent to
      glutamatergic synapses can release glutamine in a temporally precise, controlled
      manner in response to glial glutamate transporter activation. Since glutamine can
      be used by neurones as a precursor for glutamate and GABA synthesis, this
      represents a potential feedback mechanism by which astrocytes can respond to
      synaptic activation and react in a way that sustains or enhances further
      communication. This would therefore represent an additional manifestation of the
      tripartite relationship between synapses and astrocytes.

PMID- 22411008
TI  - Kv1.1-dependent control of hippocampal neuron number as revealed by mosaic
      analysis with double markers.
AB  - Megencephaly, or mceph, is a spontaneous frame-shift mutation of the mouse Kv1.1
      gene. This mceph mutation results in a truncated Kv1.1 channel alpha-subunit
      without the channel pore domain or the voltage sensor. Interestingly, mceph/mceph
      mouse brains are enlarged and - unlike wild-type mouse brains - they keep growing
      throughout adulthood, especially in the hippocampus and ventral cortex. We used
      mosaic analysis with double markers (MADM) to identify the underlying mechanism.
      In mceph-MADM6 mice with only a small fraction of neurons homozygous for the
      mceph mutation, those homozygous mceph/mceph neurons in the hippocampus are more
      abundant than wild-type neurons produced by sister neural progenitors. In
      contrast, neither mceph/mceph astrocytes, nor neurons in the adjacent dorsal
      cortex (including the entorhinal and parietal cortex) exhibited overgrowth in the
      adult brain. The sizes of mceph/mceph hippocampal neurons were comparable to
      mceph/+ or wild-type neurons. Our mosaic analysis reveals that loss of Kv1.1
      function causes an overproduction of hippocampal neurons, leading to an enlarged
      brain phenotype.

PMID- 22411009
TI  - Regulation of ventral surface CO2/H+-sensitive neurons by purinergic signalling.
AB  - Central chemoreception is the mechanism by which the brain regulates breathing in
      response to changes in tissue CO(2)H+. A brainstem region called the
      retrotrapezoid nucleus (RTN) contains a population of CO2/H+-sensitive neurons
      that appears to function as an important chemoreceptor. Evidence also indicates
      that CO2-evoked ATP release from RTN astrocytes modulates activity of CO2/H+
      sensitive neurons; however, the extent to which purinergic signalling contributes
      to chemoreception by RTN neurons is not clear and the mechanism(s) underlying
      CO2/H+-evoked ATP release is not fully elucidated. The goals of this study are to
      determine the extent to which ATP contributes to RTN chemoreception both in vivo
      and in vitro, and whether purinergic drive to chemoreceptors relies on
      extracellular Ca(2+) or gap junction hemichannels. We also examine the possible
      contribution of P2Y1 receptors expressed in the RTN to the purinergic drive to
      breathe.We show that purinergic signalling contributes, in part, to the CO(2)/H+
      sensitivity of RTN neurons. In vivo, phrenic nerve recordings of respiratory
      activity in adult rats show that bilateral injections of pyridoxal-phosphate-6
      azophenyl-2',4'-disulfonate (PPADS, a P2 receptor blocker) decreased the
      ventilatory response to CO2 by 30%. In vitro, loose-patch recordings from RTN
      neurons show that P2 receptor blockers decreased responsiveness to both 10% and
      15% CO2 also by 30%. In the slice, the contribution of purinergic signalling to
      RTN chemoreception did not increase with temperature (22-35?C) and was retained
      in low extracellular Ca2+ medium. Conversely, the gap junction blockers
      carbenoxolone and cobalt decreased neuronal CO2/H+ sensitivity by an amount
      similar to P2 receptor antagonists. Inhibition of the P2Y1 receptor in the RTN
      had no effect on CO2 responsivness in vitro or in vivo; thus, the identity of P2
      receptors underlying the purinergic component of RTN chemoreception remains
      unknown. These results support the possibility that CO2/H+-evoked ATP release is
      mediated by a mechanism involving gap junction hemichannels.

PMID- 22411010
TI  - Sodium channels, the electrogenisome and the electrogenistat: lessons and
      questions from the clinic.
AB  - In the six decades that have followed the work of Hodgkin and Huxley, multiple
      generations of neuroscientists and biophysicists have built upon their pivotal
      contributions. It is now clear that, in mammals, nine genes encode nine distinct
      voltage-gated sodium channels with different amino acid sequences and different
      physiological and pharmacological properties. The different sodium channel
      isoforms produce a multiplicity of distinct sodium currents with different time
      dependent characteristics and voltage dependencies, which interact with each
      other and with the currents produced by other channels (including calcium and
      potassium channels) to shape neuronal firing patterns. Expression of these sodium
      channel isoforms is highly dynamic, both in the normal nervous system, and in the
      injured nervous system. Recent research has shed light on the roles of sodium
      channels in human disease, a development that may open up new therapeutic
      strategies. This article examines the pain-signalling system as an example of a
      neuronal network where multiple sodium channel isoforms play complementary roles
      in electrogenesis and a strong link with human disease has been established.
      Recent research suggests that it may be possible to target specific sodium
      channel isoforms that drive hyperexcitability in pain-signalling neurons, thereby
      providing new therapeutic strategies for chronic pain, and providing an
      illustration of the impact of the Hodgkin-Huxley legacy in the clinical domain.

PMID- 22411011
TI  - The conductance of red blood cells from sickle cell patients: ion selectivity and
      inhibitors.
AB  - The abnormally high cation permeability in red blood cells (RBCs) from patients
      with sickle cell disease (SCD) occupies a central role in pathogenesis. Sickle
      RBC properties are notably heterogeneous, however, thus limiting conventional
      flux techniques that necessarily average out the behaviour of millions of cells.
      Here we use the whole-cell patch configuration to characterise the permeability
      of single RBCs from patients with SCD in more detail. A non-specific cation
      conductance was reversibly induced upon deoxygenation and was permeable to both
      univalent (Na+, K+, Rb+) and also divalent (Ca2+, Mg2+) cations. It was sensitive
      to the tarantula spider toxin GsMTx-4. Mn2+ caused partial, reversible
      inhibition. The aromatic aldehyde o-vanillin also irreversibly inhibited the
      deoxygenation-induced conductance, partially at 1mM and almost completely at 5mM.
      Nifedipine, amiloride and ethylisopropylamiloride were ineffective. In oxygenated
      RBCs, the current was pH sensitive showing a marked increase as pH fell from 7.4
      to 6, with no change apparent when pH was raised from 7.4 to 8. The effects of
      acidification and deoxygenation together were not additive. Many features of this
      deoxygenation-induced conductance (non-specificity for cations, permeability
      toCa2+ andMg2+, pH sensitivity, reversibility, partial inhibition by DIDS and
      Mn2+) are shared with the flux pathway sometimes referred to as Psickle.
      Sensitivity to GsMTx-4 indicates its possible identity as a stretch-activated
      channel. Sensitivity to o-vanillin implies that activation requires HbS
      polymerisation but since the conductance was observed in whole-cell patches,
      results suggest that bulk intracellular Hb is not involved; rather a membrane
      bound subfraction is responsible for channel activation. The ability to record
      P(sickle)-like activity in single RBCs will facilitate further studies and
      eventual molecular identification of the pathway involved.

PMID- 22411012
TI  - Patterned control of human locomotion.
AB  - There is much experimental evidence for the existence of biomechanical
      constraints which simplify the problem of control of multi-segment movements. In
      addition, it has been hypothesized that movements are controlled using a small
      set of basic temporal components or activation patterns, shared by several
      different muscles and reflecting global kinematic and kinetic goals. Here we
      review recent studies on human locomotion showing that muscle activity is
      accounted for by a combination of few basic patterns, each one timed at a
      different phase of the gait cycle. Similar patterns are involved in walking and
      running at different speeds, walking forwards or backwards, and walking under
      different loading conditions. The corresponding weights of distribution to
      different muscles may change as a function of the condition, allowing highly
      flexible control. Biomechanical correlates of each activation pattern have been
      described, leading to the hypothesis that the co-ordination of limb and body
      segments arises from the coupling of neural oscillators between each other and
      with limb mechanical oscillators. Muscle activations need only intervene during
      limited time epochs to force intrinsic oscillations of the system when energy is
      lost.

PMID- 22411013
TI  - Neurons respond directly to mechanical deformation with pannexin-mediated ATP
      release and autostimulation of P2X7 receptors.
AB  - Mechanical deformation produces complex effects on neuronal systems, some of
      which can lead to dysfunction and neuronal death. While astrocytes are known to
      respond to mechanical forces, it is not clear whether neurons can also respond
      directly. We examined mechanosensitive ATP release and the physiological response
      to this release in isolated retinal ganglion cells. Purified ganglion cells
      released ATP upon swelling. Release was blocked by carbenoxolone, probenecid or
      peptide (10)panx, implicating pannexin channels as conduits. Mechanical stretch
      of retinal ganglion cells also triggered a pannexin-dependent ATP release. Whole
      cell patch clamp recording demonstrated that mild swelling induced the activation
      of an Ohmic cation current with linear kinetics. The current was inhibited by
      removal of extracellular ATP with apyrase, by inhibition of the P2X(7) receptor
      with A438079, zinc, or AZ 10606120, and by pannexin blockers carbenoxolone and
      probenecid. Probenecid also inhibited the regulatory volume decrease observed
      after swelling isolated neurons. Together, these observations indicate mechanical
      strain triggers ATP release directly from retinal ganglion cells and that this
      released ATP autostimulates P2X(7) receptors. Since extracellular ATP levels in
      the retina increase with elevated intraocular pressure, and stimulation of P2X(7)
      receptors on retinal ganglion cells can be lethal, this autocrine response may
      impact ganglion cells in glaucoma. It remains to be determined whether the
      autocrine stimulation of purinergic receptors is a general response to a
      mechanical deformation in neurons, or whether preventing ATP release through
      pannexin channels and blocking activation of the P2X(7) receptor, is
      neuroprotective for stretched neurons.

PMID- 22411014
TI  - Expression of gastrin-releasing peptide is increased by prolonged stretch of
      human myometrium, and antagonists of its receptor inhibit contractility.
AB  - Increased uterine stretch appears to increase the risk of preterm labour, but the
      mechanism is unknown. The aim of this study was to identify factors that mediate
      the effect of stretch on human myometrium.Myometrial explants, prepared from
      biopsies obtained at elective caesarean delivery, were either studied acutely, or
      were maintained in prolonged culture (up to 65 h) under tension with either a 0.6
      g or a 2.4 g mass, and compared using in vitro contractility, whole genome array,
      and qRT-PCR. Tissue held at tonic stretch with the 2.4 g mass for either 24 or 65
      h showed increased potassium chloride (KCl)-induced and oxytocin-induced
      contractility compared with that held with the 0.6 g mass. Gene array identified
      62 differentially expressed transcripts after 65 h exposure to increased stretch.
      Two probes for gastrin-releasing peptide (GRP), a known stimulatory agonist of
      smooth muscle, were among the top five up-regulated by stretch (3.4-fold and 2.0
      fold). Up-regulation of GRP mRNA by stretch was confirmed in a separate series of
      10 samples using quantitative RT-PCR (qRT-PCR) (2.8-fold, P =0.01). GRP
      stimulated contractions acutely when added to freshly obtained myometrial strips
      in 2 out of 9 cases, but Western blot demonstrated expression of the GRP receptor
      in 9 out of a further 9 cases. Prolonged incubation of stretched explants in the
      GRP antagonists PD-176252 or RC-3095 (65 and 24 h, respectively) significantly
      reduced KCl- and oxytocin-induced contractility.Tonic stretch of human myometrium
      increases contractility and stimulates the expression of a known smooth muscle
      stimulatory agonist, GRP. Incubation of myometrium with GRP receptor antagonists
      attenuates the effect of stretch. GRP may be a target for novel therapies to
      reduce the risk of preterm birth in multiple pregnancy.

PMID- 22411015
TI  - Long-lasting potentiation of hippocampal synaptic transmission by direct cortical
      input is mediated via endocannabinoids.
AB  - Hippocampal CA1 pyramidal neurons receive sensory inputs from the entorhinal
      cortex directly through the perforant path (PP) and indirectly through Schaffer
      collaterals (SC). Direct cortical inputs to CA1 pyramidal neurons through the PP
      provide instructive signals for hippocampal long-term synaptic plasticity.
      However, the molecules conveying synaptic signalling in this new form of
      heterosynaptic plasticity remain unclear. Endocannabinoids, important endogenous
      signalling mediators, modulate synaptic efficacy primarily through inhibition of
      GABAergic or glutamatergic synaptic transmission via presynaptically expressed
      CB1 receptors. Here, we report that pairing of direct and indirect cortical
      inputs to CA1 pyramidal neurons resulted in a long-lasting potentiation of
      synaptic responses at SC synapses, but not at the PP. The pairing-potentiated
      synaptic transmission at the SC was accompanied by a reduced ratio of paired
      pulse facilitation (PPR). Enhanced synaptic response at the SC by pairing of PP
      SC stimuli is Ca(2+) dependent and requires the presence of functional GABAergic
      and glutamatergic synaptic transmissions and activation of group I metabotropic
      glutamate receptors. Pharmacological inhibition or genetic deletion of the CB1
      receptor eliminated the pairing-induced long-term synaptic plasticity and
      decreased PPR at the SC. The potentiation induced by pairing of PP-SC stimuli
      primarily is the glutamatergic synaptic transmission. While the pairing-induced
      long-lasting potentiation of synaptic response was blocked by inhibitors for
      diacylglycerol lipase (DGL), which biosynthesizes 2-AG, inhibition of
      monoacylglycerol lipase (MAGL), which metabolizes 2-AG, facilitated the
      potentiation at SC synapses by pairing of weak PP-SC stimuli. Our results suggest
      that 2-AG functions as a signalling mediator tuning synaptic efficacy at the
      proximal synapses of hippocampal CA1 pyramidal neurons while direct and indirect
      cortical inputs to the same neurons are spatiotemporally primed.

PMID- 22411017
TI  - Provocative F wave in the diagnosis of nonspecific neurogenic-type thoracic
      outlet syndrome.
AB  - OBJECTIVE: Thoracic outlet syndrome (TOS) is defined as a constellation of
      clinical symptoms caused by the entrapment of neurovascular structures
      (subclavian vessels and the brachial plexus) en route to the upper limb via the
      superior thoracic outlet. Nonspecific neurogenic TOS is not easy to diagnose
      because there is no investigational technique that has proven to be the
      diagnostic gold standard. DESIGN: In this study, our aim was to investigate the
      role of provocative F response in the diagnosis of nonspecific neurogenic TOS. F
      wave analysis of median and ulnar nerves in neutral and provocative maneuvers was
      carried out in 21 patients with a clinical diagnosis of nonspecific neurogenic
      TOS and in 15 healthy volunteers. RESULTS: All findings were within reference
      range in both groups, and no statistical difference was noted among subject
      groups, with or without provocative maneuvers. CONCLUSIONS: We conclude that the
      nonspecific neurogenic TOS is a temporary compression process that does not
      result in a structural damage on the nerve; therefore, significant
      electrophysiologic changes are not elicited.

PMID- 22411016
TI  - Effect of the glycocalyx layer on transmission of interstitial flow shear stress
      to embedded cells.
AB  - In this paper, a simple theoretical model is developed to describe the
      transmission of force from interstitial fluid flow to the surface of a cell
      covered by a proteoglycan / glycoprotein layer (glycocalyx) and embedded in an
      extracellular matrix. Brinkman equations are used to describe flow through the
      extracellular matrix and glycocalyx layers and the solid mechanical stress
      developed in the glycocalyx by the fluid flow loading is determined. Using
      reasonable values for the Darcy permeability of extracellular matrix and
      glycocalyx layers and interstitial flow velocity, we are able to estimate the
      fluid and solid shear stresses imposed on the surface of embedded vascular,
      cartilage and tumor cells in vivo and in vitro. The principal finding is that the
      surface solid stress is typically one to two orders of magnitude larger than the
      surface fluid stress. This indicates that interstitial flow shear stress can be
      sensed by the cell surface glycocalyx, supporting numerous recent observations
      that interstitial flow can induce mechanotransduction in embedded cells. This
      study may contribute to understanding of interstitial flow-related mechanobiology
      in embryogenesis, tumorigenesis, tissue physiology and diseases and has
      implications in tissue engineering.

PMID- 22411018
TI  - Acute atraumatic hip dislocation in an adult with rheumatoid arthritis.
AB  - There are no reports of atraumatic hip subluxation and dislocation in the adult
      patient with rheumatoid arthritis (RA). This rare phenomenon is most prevalent in
      patients with congenital hip dislocation, von Recklinghausen disease, tumor
      infiltration, connective tissue disorders, and juvenile rheumatoid arthritis. We
      report an acute atraumatic dislocation of the hip in an adult patient with RA. We
      believe that two factors contributed to the patient's atraumatic dislocation: a
      shallow but appropriately positioned acetabulum and erosive RA with substantiate
      panus formation. Similar to previous reports, there was a rent or capsular defect
      that may have contributed to the mechanism of dislocation. Physicians should be
      aware that, although rare, a de novo atraumatic hip dislocation is a possibility
      in a patient with a long-standing history of RA and hip pain. Distinguishing
      features of this case include the acuteness of the dislocation, the absence of
      previous symptoms, and adult-onset RA.

PMID- 22411019
TI  - A review of the medical treatment of pediatric glaucomas at Moorfields Eye
      Hospital.
AB  - PURPOSE: To report on the medical treatments used for pediatric glaucomas.
      PATIENTS AND METHODS: A retrospective case series consisting of reviewing the
      medical notes of pediatric glaucoma patients under the care of the Glaucoma
      Service at Moorfields Eye Hospital NHS Foundation Trust. The medical notes of 200
      patients were selected. The following outcomes were assessed: (1) the use of
      individual medical therapies; (2) the intraocular pressure (IOP) reduction effect
      of individual medicines; (3) the reporting of side effects. RESULTS: Medicines
      were prescribed 1592 times (200 patients). The median % IOP reduction for
      latanoprost 50 mcg/mL was -17.2% and for the topical beta blockers was -17.7% (as
      monotherapy), with no statistical difference in IOP-lowering effect between all
      the medicines (P=0.19). Side effects were reported in 19.5% of all patients-the
      highest occurrence with brimonidine tartrate 0.2% (in 17% patients) and the
      lowest occurrence with the prostaglandin analogue and prostamide medicines (in
      3.8% patients). The combination of dorzolamide hydrochloride 2%, timolol maleate
      0.5% had the greatest persistence of 1 year. CONCLUSIONS: The IOP-lowering
      effects of all the glaucoma medicines were not significantly different although
      the combination of dorzolamide hydrochloride 2%, timolol maleate 0.5% had the
      greatest persistence.

PMID- 22411021
TI  - Adherence to glaucoma medication: the effect of interventions and association
      with personality type.
AB  - PURPOSE: To determine whether multiple interventions influence adherence to
      glaucoma medication and to study the relationship between personality type and
      adherence. METHODS: Eighty patients with glaucoma using prostaglandin monotherapy
      were prospectively randomized to an intervention or a nonintervention group. Over
      a 5-month period, the intervention group received monthly automated telephone
      calls reminding them to take their glaucoma medications. At month 3, the
      intervention group had an office visit with their physician and received
      education regarding their disease and treatment. The nonintervention group
      returned at the end of the study period. Adherence was directly measured with an
      electronic monitoring cap. Outcome measures were adherence rate and therapeutic
      coverage. Patients completed the Minnesota Multiphasic Personality Inventory-2.
      RESULTS: Thirty-eight patients were randomized to the intervention group and 42
      were randomized to the nonintervention group. Mean adherence rate for the
      intervention group over 5 months was 76% and for the nonintervention group, 81%.
      For the intervention group, adherence did not change significantly after the
      midstudy visit (P=0.233). No difference existed between the intervention and
      nonintervention groups before (P=0.456) or after (P=0.134) the midstudy
      intervention visit. The Minnesota Multiphasic Personality Inventory-2 personality
      scales for depression (P=0.01) and hypochondriasis (P>0.0001) were significantly
      associated with poorer adherence. CONCLUSIONS: Monthly automated telephone
      reminders, a 1-time educational session, and increased contact with a physician
      did not improve adherence rate with glaucoma medications. Depression and
      hypochondriasis personality types were related to poor adherence and highlight
      the role of psychosocial factors in medication adherence.

PMID- 22411020
TI  - Association of the optic disc structure with the use of antihypertensive
      medications: the thessaloniki eye study.
AB  - PURPOSE: To investigate the association of antihypertensive medications with
      optic disc structure by blood pressure (BP) level, in nonglaucoma subjects.
      DESIGN: Cross-sectional, population-based study. METHODS: A subset of
      Thessaloniki Eye Study participants was included in this study. Subjects were
      interviewed for medical history and underwent extensive ophthalmic examination,
      BP measurement, and optic disc imaging with the Heidelberg retinal tomograph.
      Subjects treated for hypertension were grouped in the following groups: (1)
      angiotensin-converting enzyme inhibitors and/or angiotensin-receptor blockers;
      (2) beta blockers and/or calcium-channel blockers; (3) diuretics alone or
      combined with others; and (4) other combinations. Cup size and cup-to-disc (C/D)
      ratio in the above groups were compared with the untreated group, using
      regression models. Analyses were rerun for subjects with systolic BP (SBP)<140 mm
      Hg, SBP>=140 mm Hg, diastolic BP (DBP)<90 mm Hg, and DBP>=90 mm Hg. RESULTS:
      Among 232 subjects, 131 were receiving antihypertensive medications. In subjects
      with DBP<90 mm Hg, all medications groups were associated with larger cup size
      and higher C/D ratio compared with the untreated group. Results were similar in
      subjects with SBP<140 mm Hg, with the exception of the beta blockers and/or
      calcium-channel blockers group. None of the medications groups were associated
      with the Heidelberg retinal tomograph parameters in those with DBP>=90 mm Hg or
      SBP>=140 mm Hg. CONCLUSIONS: All classes of antihypertensive medications were
      associated with larger cup size and higher C/D ratio in subjects with either
      DBP<90 mm Hg or SBP<140 mm Hg. These results suggest that there is no specific
      medication-related effect on optic disc structure, and the associations found are
      mediated through the hypotensive effect of antihypertensive medications.

PMID- 22411023
TI  - Trajectory Learning for Robot Programming by Demonstration Using Hidden Markov
      Model and Dynamic Time Warping.
AB  - The main objective of this paper is to develop an efficient method for learning
      and reproduction of complex trajectories for robot programming by demonstration.
      Encoding of the demonstrated trajectories is performed with hidden Markov model,
      and generation of a generalized trajectory is achieved by using the concept of
      key points. Identification of the key points is based on significant changes in
      position and velocity in the demonstrated trajectories. The resulting sequences
      of trajectory key points are temporally aligned using the multidimensional
      dynamic time warping algorithm, and a generalized trajectory is obtained by
      smoothing spline interpolation of the clustered key points. The principal
      advantage of our proposed approach is utilization of the trajectory key points
      from all demonstrations for generation of a generalized trajectory. In addition,
      variability of the key points' clusters across the demonstrated set is employed
      for assigning weighting coefficients, resulting in a generalization procedure
      which accounts for the relevance of reproduction of different parts of the
      trajectories. The approach is verified experimentally for trajectories with two
      different levels of complexity. 

PMID- 22411022
TI  - Complete failure of insulin-transmitted signaling, but not obesity-induced
      insulin resistance, impairs respiratory chain function in muscle.
AB  - The role of mitochondrial dysfunction in the development of insulin resistance
      and type 2 diabetes remains controversial. In order to specifically define the
      relationship between insulin receptor (InsR) signaling, insulin resistance,
      hyperglycemia, hyperlipidemia and mitochondrial function, we analyzed
      mitochondrial performance of insulin-sensitive, slow-oxidative muscle in four
      different mouse models. In obese but normoglycemic ob/ob mice as well as in obese
      but diabetic mice under high-fat diet, mitochondrial performance remained
      unchanged even though intramyocellular diacylglycerols (DAGs), triacylglycerols
      (TAGs), and ceramides accumulated. In contrast, in muscle-specific InsR knockout
      (MIRKO) and streptozotocin (STZ)-treated hypoinsulinemic, hyperglycemic mice,
      levels of mitochondrial respiratory chain complexes and mitochondrial function
      were markedly reduced. In STZ, but not in MIRKO mice, this was caused by reduced
      transcription of mitochondrial genes mediated via decreased PGC-1alpha
      expression. We conclude that mitochondrial dysfunction is not causally involved
      in the pathogenesis of obesity-associated insulin resistance under normoglycemic
      conditions. However, obesity-associated type 2 diabetes and accumulation of DAGs
      or TAGs is not associated with impaired mitochondrial function. In contrast,
      chronic hypoinsulinemia and hyperglycemia as seen in STZ-treated mice as well as
      InsR deficiency in muscle of MIRKO mice lead to mitochondrial dysfunction. We
      postulate that decreased mitochondrial mass and/or performance in skeletal muscle
      of non-diabetic, obese or type 2 diabetic, obese patients observed in clinical
      studies must be explained by genetic predisposition, physical inactivity, or
      other still unknown factors.

PMID- 22411024
TI  - Statistical Mechanics-Inspired Modeling of Heterogeneous Packet Transmission in
      Communication Networks.
AB  - This paper presents the qualitative nature of communication network operations as
      abstraction of typical thermodynamic parameters (e.g., order parameter,
      temperature, and pressure). Specifically, statistical mechanics-inspired models
      of critical phenomena (e.g., phase transitions and size scaling) for
      heterogeneous packet transmission are developed in terms of multiple intensive
      parameters, namely, the external packet load on the network system and the packet
      transmission probabilities of heterogeneous packet types. Network phase diagrams
      are constructed based on these traffic parameters, and decision and control
      strategies are formulated for heterogeneous packet transmission in the network
      system. In this context, decision functions and control objectives are derived in
      closed forms, and the pertinent results of test and validation on a simulated
      network system are presented. 

PMID- 22411025
TI  - Chaotic Dynamics in Social Foraging Swarms-An Analysis.
AB  - This paper investigates the chaotic characteristics in the dynamics of an
      aggregating swarm model. The range of the parameters of the swarm model is
      determined for which chaos exists in the dynamics. The trajectories of the
      individuals are simulated, and the stable, limit cyclic, and chaotic behaviors
      are demonstrated. The existence of chaos in the swarm is determined by the
      maximum Lyapunov exponent. The computer simulation supports the results obtained
      by theoretical analysis. 

PMID- 22411026
TI  - An Accelerated-Limit-Crossing-Based Multilevel Algorithm for the p-Median
      Problem.
AB  - In this paper, we investigate how to design an efficient heuristic algorithm
      under the guideline of the backbone and the fat, in the context of the p-median
      problem. Given a problem instance, the backbone variables are defined as the
      variables shared by all optimal solutions, and the fat variables are defined as
      the variables that are absent from every optimal solution. Identification of the
      backbone (fat) variables is essential for the heuristic algorithms exploiting
      such structures. Since the existing exact identification method, i.e., limit
      crossing (LC), is time consuming and sensitive to the upper bounds, it is hard to
      incorporate LC into heuristic algorithm design. In this paper, we develop the
      accelerated-LC (ALC)-based multilevel algorithm (ALCMA). In contrast to LC which
      repeatedly runs the time-consuming Lagrangian relaxation (LR) procedure, ALC is
      introduced in ALCMA such that LR is performed only once, and every backbone (fat)
      variable can be determined in O(1) time. Meanwhile, the upper bound sensitivity
      is eliminated by a dynamic pseudo upper bound mechanism. By combining ALC with
      the pseudo upper bound, ALCMA can efficiently find high-quality solutions within
      a series of reduced search spaces. Extensive empirical results demonstrate that
      ALCMA outperforms existing heuristic algorithms in terms of the average solution
      quality. 

PMID- 22411027
TI  - Adapting the Right Measures for Pattern Discovery: A Unified View.
AB  - This paper presents a unified view of interestingness measures for interesting
      pattern discovery. Specifically, we first provide three necessary conditions for
      interestingness measures being used for association pattern discovery. Then, we
      reveal one desirable property for interestingness measures: the support-ascending
      conditional antimonotone property (SA-CAMP). Along this line, we prove that the
      measures possessing SA-CAMP are suitable for pattern discovery if the itemset
      traversal structure is defined by a support-ascending set enumeration tree. In
      addition, we provide a thorough study on the family of the generalized mean (GM)
      measure and show their appealing properties, which are exploited for developing
      the GMiner algorithm for finding interesting association patterns. Finally,
      experimental results show that GMiner can efficiently identify interesting
      patterns based on SA-CAMP of the GM measure, even at an extremely low level of
      support. 

PMID- 22411028
TI  - PM(2.5) in the central part of Upper Silesia, Poland: concentrations, elemental
      composition, and mobility of components.
AB  - The paper discusses ambient concentrations of PM(2.5) (ambient fine particles)
      and of 29 PM(2.5)-related elements in Zabrze and Katowice, Poland, in 2007. The
      elemental composition of PM(2.5) was determined using energy dispersive X-ray
      fluorescence (EDXRF). The mobility (cumulative percentage of the water-soluble
      and exchangeable fractions of an element in its total concentration) of 18
      PM(2.5)-related elements in Zabrze and Katowice was computed by using sequential
      extraction and EDXRF combined into a simple method. The samples were extracted
      twice: in deionized water and in ammonium acetate. In general, the mobility and
      the concentrations of the majority of the elements were the same in both cities.
      S, Cl, K, Ca, Zn, Br, Ba, and Pb in both cities, Ti and Se in Katowice, and Sr in
      Zabrze had the mobility greater than 70%. Mobility of typical crustal elements,
      Al, Si, and Ti, because of high proportion of their exchangeable fractions in PM,
      was from 40 to 66%. Mobility of Fe and Cu was lower than 30%. Probable sources of
      PM(2.5) were determined by applying principal component analysis and multiple
      regression analysis and computing enrichment factors. Great part of PM(2.5) (78%
      in Katowice and 36% in Zabrze) originated from combustion of fuels in domestic
      furnaces (fossil fuels, biomass and wastes, etc.) and liquid fuels in car
      engines. Other identified sources were: power plants, soil, and roads in Zabrze
      and in Katowice an industrial source, probably a non-ferrous smelter or/and a
      steelwork, and power plants.

PMID- 22411029
TI  - Climate change or climate cycles? Snowpack trends in the Olympic and Cascade
      Mountains, Washington, USA.
AB  - Climate change could significantly influence seasonal streamflow and water
      availability in the snowpack-fed watersheds of Washington, USA. Descriptions of
      snowpack decline often use linear ordinary least squares (OLS) models to quantify
      this change. However, the region's precipitation is known to be related to
      climate cycles. If snowpack decline is more closely related to these cycles, an
      OLS model cannot account for this effect, and thus both descriptions of trends
      and estimates of decline could be inaccurate. We used intervention analysis to
      determine whether snow water equivalent (SWE) in 25 long-term snow courses within
      the Olympic and Cascade Mountains are more accurately described by OLS (to
      represent gradual change), stationary (to represent no change), or step
      stationary (to represent climate cycling) models. We used Bayesian information
      theoretic methods to determine these models' relative likelihood, and we found 90
      models that could plausibly describe the statistical structure of the 25 snow
      courses' time series. Posterior model probabilities of the 29 "most plausible"
      models ranged from 0.33 to 0.91 (mean = 0.58, s = 0.15). The majority of these
      time series (55%) were best represented as step-stationary models with a single
      breakpoint at 1976/77, coinciding with a major shift in the Pacific Decadal
      Oscillation. However, estimates of SWE decline differed by as much as 35% between
      statistically plausible models of a single time series. This ambiguity is a
      critical problem for water management policy. Approaches such as intervention
      analysis should become part of the basic analytical toolkit for snowpack or other
      climatic time series data.

PMID- 22411030
TI  - Assessment of big floods in the Eastern Black Sea Basin of Turkey.
AB  - In this study, general knowledge and some details of the floods in Eastern Black
      Sea Basin of Turkey are presented. Brief hydro-meteorological analysis of
      selected nine floods and detailed analysis of the greatest flood are given. In
      the studied area, 51 big floods have taken place between 1955-2005 years, causing
      258 deaths and nearly US $500,000,000 of damage. Most of the floods have occurred
      in June, July and August. It is concluded that especially for the rainstorms that
      have caused significantly damages, the return periods of the rainfall heights and
      resultant flood discharges have gone up to 250 and 500 years, respectively. A
      general agreement is observed between the return periods of rains and resultant
      floods. It is concluded that there has been no significant climate change to
      cause increases in flood harms. The most important human factors to increase the
      damage are determined as wrong and illegal land use, deforestation and wrong
      urbanization and settlement, psychological and technical factors. Some structural
      and non-structural measures to mitigate flood damages are also included in the
      paper. Structural measures include dykes and flood levees. Main non-structural
      measures include flood warning system, modification of land use, watershed
      management and improvement, flood insurance, organization of flood management
      studies, coordination between related institutions and education of the people
      and informing of the stakeholders.

PMID- 22411031
TI  - Model-driven development of covariances for spatiotemporal environmental health
      assessment.
AB  - Known conceptual and technical limitations of mainstream environmental health
      data analysis have directed research to new avenues. The goal is to deal more
      efficiently with the inherent uncertainty and composite space-time heterogeneity
      of key attributes, account for multi-sourced knowledge bases (health models,
      survey data, empirical relationships etc.), and generate more accurate
      predictions across space-time. Based on a versatile, knowledge synthesis
      methodological framework, we introduce new space-time covariance functions built
      by integrating epidemic propagation models and we apply them in the analysis of
      existing flu datasets. Within the knowledge synthesis framework, the Bayesian
      maximum entropy theory is our method of choice for the spatiotemporal prediction
      of the ratio of new infectives (RNI) for a case study of flu in France. The space
      time analysis is based on observations during a period of 15 weeks in 1998-1999.
      We present general features of the proposed covariance functions, and use these
      functions to explore the composite space-time RNI dependency. We then implement
      the findings to generate sufficiently detailed and informative maps of the RNI
      patterns across space and time. The predicted distributions of RNI suggest
      substantive relationships in accordance with the typical physiographic and
      climatologic features of the country.

PMID- 22411032
TI  - Monitoring nitrogen deposition in typical forest ecosystems along a large
      transect in China.
AB  - The nitrogen (N) deposition fluxes were investigated in eight typical forest
      ecosystems along the North-South Transect of Eastern China (NSTEC; based on the
      ChinaFLUX network) by ion-exchange resin (IER) columns from May 2008 to April
      2009. Our results demonstrated that the method of IER columns was both labor cost
      saving and reliable for measuring dissolved inorganic nitrogen (DIN) deposition
      at the remote forest stations. The deposition of DIN in the throughfall ranged
      from 1.3 to 29.5 kg N ha(-1) a(-1), increasing from north to south along NSTEC.
      The relatively high average ratio of ammonium to nitrate in deposition (1.83)
      indicated that the N deposition along the NSTEC in China mostly originated in
      farming and animal husbandry rather than in industry and vehicle activities. For
      seasonal variability, the DIN deposition showed a single peak in the growing
      season in the northern part of NSTEC, while, in the southern part, it exhibited
      double-peaks in the early spring and the mid-summer, respectively. On the annual
      scale, the DIN deposition variations of the eight sites could be mainly explained
      by precipitation and the distances from forest stations to provincial capital
      cities.

PMID- 22411033
TI  - Bariatric surgery highlights in the International Journal of Obesity.

PMID- 22411035
TI  - Atlantoaxial rotatory dislocation (AARD) in pediatric age: MRI study on
      conservative treatment with Philadelphia collar--experience of nine consecutive
      cases.
AB  - PURPOSE: Atlantoaxial rotatory fixation and atlantoaxial rotatory subluxation are
      the most frequent manifestations of atlantoaxial rotatory dislocation (AARD) in
      pediatric population and are often treated conservatively. The objective of this
      study is to correlate the changes highlighted on MRI T2-weighted and STIR
      sequences with the duration of conservative treatment. METHODS: We analyzed nine
      consecutive patients treated surgically between 1 Jan 2006 and 1 Jan 2010 at the
      Policlinico Umberto I of Rome. All patients underwent cervical X-ray, computed
      tomography and magnetic resonance imaging (MRI) (T1 and T2-weighted, STIR, angio
      MRI). All patients were treated with bed rest, muscle relaxants and cervical
      collar, and radiological follow-up with MRI and cervical X-ray was performed.
      RESULTS: According to Fielding's classification, we observed seven patients with
      a type 1 subluxation and two patients with a type II subluxation. In type 1, STIR
      and T2 sequences showed a hyperintensity in the alar and capsular ligaments and
      in the posterior ligamentous system, with integrity of the transverse ligament
      (LTA). In type 2, the hyperintensity also involved the LTA. During the follow-up,
      MRI showed a progressive reduction until the disappearance of the hyperintensity
      described, which was followed by a break with orthotic immobilization.
      CONCLUSIONS: MRI with STIR sequences appears to be useful in addressing the
      duration of conservative treatment in AARD.

PMID- 22411037
TI  - Cement leakage: safety of minimally invasive surgical techniques in the treatment
      of multiple myeloma vertebral lesions.
AB  - PURPOSE: To evaluate and address the safety of vertebroplasty (VP) and
      kyphoplasty (KP) in terms of rate and type of cement leakage in the treatment of
      Multiple Myeloma (MM) vertebral fractures. METHODS: A total number of 37 treated
      vertebrae were evaluated post-operatively by using standard X-rays and CT scan
      looking for a cement leakage. VP was done using a monoportal approach in all
      cases (18 treated levels, group A), while KP was done using a monopedicular
      approach in 9 levels (group B1) and using a bipedicular approach in the remaining
      10 levels (group B2). A computed tomography was used to establish the presence of
      any cement leakage and to determine its localization. RESULTS: Vertebral
      augmentation through VP and KP provides immediate pain relief and an improvement
      of the quality of life of patients affected by MM but it is gravated by high risk
      of cement leakage. Cement extravasation occurred in 27.7% of total VP procedures
      and in 21.05% of total KP procedures, but considering the whole number of treated
      levels, it was more common in multi-level VP and in bipedicular KP, in which a
      higher quantity of cement was employed. CONCLUSIONS: KP procedure in these
      patients is slightly less risky but we suggest doing it with a monopedicular
      approach. It's mandatory to use an high viscosity cement and we suggest not to
      use an amount of PMMA over 2 cc and a previous treatment with bone marrow
      transplant is related to a lower risk of cement leakage.

PMID- 22411036
TI  - Free-hand pedicle screws insertion technique in the treatment of 120 consecutive
      scoliosis cases operated without use of intraoperative neurophysiological
      monitoring.
AB  - PURPOSE: We present 120 patients (37 males, 83 females) affected by thoracic
      lumbar scoliosis, treated by posterior instrumented arthrodesis with the
      insertion of pedicle screws by "free hand technique", without any image guided
      system, radioscopy use during insertion or intraoperative neurophysiological
      monitoring. METHODS: Seventy-two (60%) patients have been treated by hybrid
      instrumentation with lumbar and thoracic screws, hooks and wires at thoracic
      levels, while the remaining 48 (40%) patients have used only lumbar and thoracic
      pedicle screws. Mean Cobb grades value of the main scoliotic curve was 73 degrees
      before surgery in patients treated by hybrid instrumentation, reduced to 37.5
      degrees  after surgery. In patients treated only by screws, mean Cobb grades
      value of the main scoliotic curve was 65 degrees , reduced to 16 degrees  after
      surgery. RESULTS: Minimum follow up has been 3 years; mean patient age at surgery
      was 15 years and 4 months. We placed a total number of 1,004 pedicle screws, 487
      of which at thoracic level. In 12 patients (10%) a total number of 20 screws were
      misplaced at postoperatory exam, without any clinical complication for the
      patients or consequences on the arthrodesis or on maintaining the correction of
      the curve. CONCLUSIONS: In our experience pedicle screws is the method that leads
      to best correction and balance on vertebral bodies, with best results at distance
      concerning correction maintaining. Our experience shows that even at thoracic
      level, pedicle screws insertion by free-hand technique is safe and reliable.

PMID- 22411038
TI  - Diffusion-weighted MR imaging in differentiation between osteoporotic and
      neoplastic vertebral fractures.
AB  - PURPOSE: To assess the usefulness of magnetic resonance imaging (MRI) with spin
      echo echo-planar diffusion-weighted imaging (SE-EPI-DWI) in differentiation
      between vertebral osteoporotic fractures and pathological neoplastic fractures.
      MATERIALS AND METHODS: Thirty-three patients with both osteoporotic or neoplastic
      vertebral fractures diagnosed with X-ray or TC were studied with MRI exam, (1.5 T
      unit) with DWI sequences. DWI sequences were qualitatively analyzed. Apparent
      diffusion coefficient (ADC) values were also determined and compared to the
      definitive histologic diagnosis. RESULTS: DWI of neoplastic lesions showed
      hyperintensity signal in 22 out of 23 cases. Mean ADC value of neoplastic
      fractures was 1.241 +/- 0.4 * 10(-3) mm(2)/s; mean ADC value of osteoporotic
      fractures was 0.646 +/- 0.368 * 10(-3) mm(2)/s. Neoplastic fractures showed ADC
      values significantly higher than osteoporotic ones (p < 0.001). DWI imaging and
      histology showed a significant correlation. CONCLUSION: DWI provides reliable
      information to support MRI diagnosis of neoplastic versus osteoporotic fractures.
      ADC value appears as a useful adjunctive parameter.

PMID- 22411039
TI  - Bioactive electrospun scaffold for annulus fibrosus repair and regeneration.
AB  - PURPOSE: Annulus fibrosus (AF) tissue engineering is gathering increasing
      interest for the development of strategies to reduce recurrent disc herniation
      (DH) rate and to increase the effectiveness of intervertebral disc regeneration
      strategies. This study evaluates the use of a bioactive microfibrous poly(L
      lactide) scaffold releasing Transforming Growth Factor (TGF)-beta1 (PLLA/TGF) for
      the repair and regeneration of damaged AF. METHODS: The scaffold was synthesized
      by electrospinning, with a direct incorporation of TGF-beta1 into the polymeric
      solution, and characterized in terms of morphology and drug release profile.
      Biological evaluation was performed with bovine AF cells (AFCs) that were
      cultured on the scaffold up to 3 weeks to quantitatively assess
      glycosaminoglycans and total collagen production, using bare electrospun PLLA as
      a control. Histological evaluation was performed to determine the thickness of
      the deposited neo-ECM. RESULTS: Results demonstrated that AFCs cultured on
      PLLA/TGF deposited a significantly greater amount of glycosaminoglycans and total
      collagen than the control, with higher neo-ECM thickness. CONCLUSIONS: PLLA/TGF
      scaffold induced an anabolic stimulus on AFCs, mimicking the ECM three
      dimensional environment of AF tissue. This bioactive scaffold showed encouraging
      results that allow envisaging an application for AF tissue engineering strategies
      and AF repair after discectomy for the prevention of recurrent DH.

PMID- 22411040
TI  - Criteria to restore the sagittal balance in deformity and degenerative
      spondylolisthesis.
AB  - PURPOSE: To present in a single source the relevant information needed to assess
      spinopelvic balance and alignment, and to estimate the amount of correction
      needed in a patient during surgical treatment. METHODS: Narrative literature
      review RESULTS: Sagittal balance can be evaluated by global balance estimates
      (sagittal vertical axis and T1 tilt). Other important parameters are the
      relationship between pelvic incidence and lumbar lordosis (spinopelvic harmony),
      between pelvic incidence and difference of thoracic kyphosis and lumbar lordosis
      (spinopelvic balance), excess of pelvic tilt, knee flexion and thoracic
      compensatory hypokyphosis. Different methods to calculate the amount of surgical
      correction needed in patients with sagittal imbalance have been based on
      combinations of these parameters. CONCLUSIONS: Relevant parameters of sagittal
      imbalance have been identified and correlated with clinical outcomes. Methods for
      calculation of surgical correction of imbalance have been proposed, but not
      validated in patients with mid-term follow-up.

PMID- 22411041
TI  - Reviewer's comment concerning "Continuing conservative care versus cross-over to
      radiofrequency kyphoplasty: a comparative effectiveness study on the treatment of
      vertebral body fractures" (doi:10.1007/s00586-012-2148-8 by R. Bornemann, M.
      Hanna, K. Kabir, H. Goost, D. C. Wirtz, R. Pflugmacher).

PMID- 22411042
TI  - An in vitro biomechanical comparison of CadiscTM-L with natural lumbar discs in
      axial compression and sagittal flexion.
AB  - INTRODUCTION: The elastomeric, monobloc disc prosthesis (CadiscTM-L, Ranier
      Technology, Cambridge, UK) aims to preserve biomechanics of an implanted spinal
      motion segment. STUDY DESIGN: This study presents the findings of an in vitro
      investigation on the effect of implantation of CadiscTM-L. Compressive stiffness,
      flexion stiffness at 10, 20, 30 and 40 Nm and the instant-axis-of-rotation (IAR)
      loci are compared before and after implantation of a MC-10 mm-6 degrees  CadiscTM
      L. METHODS: Fresh frozen human monosegmental lumbar spines (n = 8) were prepared,
      potted and tested in an environmentally controlled chamber to simulate in vivo
      conditions. Specimens were preconditioned by loading to 500 N for 30 min.
      Compressive stiffness of the specimen was determined by applying pure compression
      of 1 kN at 250 N/s via a loading roller positioned at the central loading axis
      (CLA). The roller was then offset 12.5 mm anterior of the CLA and the loading
      regime repeated to test specimens in flexion. Bending moments were calculated
      from the applied load and corresponding flexion angle. The IAR locus was tracked
      by a motion-tracking camera. RESULTS: Compressive stiffness was reduced by 50 %
      (p = 0.0005), flexion stiffness was not statistically significantly reduced (40 %
      reduction, p > 0.05). IAR locus maintained a 'horizontal figure of eight'
      characteristic. Change in the locus width in the AP plane of 6.4 mm (p = 0.06)
      and height in the SI plane of 1.3 mm (p = 0.44) were not significant. The
      centroid was displaced 4.44 mm (p = 0.0019) and 5.44 mm (p = 0.025) at 3 degrees 
      and 6 degrees  flexion, respectively. CONCLUSIONS: Implantation of CadiscTM-L
      caused a reduction in axial stiffness, but maintained disc height and flexion
      stiffness. IAR loci remained mobile without large displacement of the centroid
      from the intact spine position.

PMID- 22411043
TI  - A negative relationship between leg length and leg cross-sectional areas in
      adults.
AB  - OBJECTIVES: These were to examine the relationship between leg cross-sectional
      areas (CSAs) and leg length while making allowance for other factors, such as
      fatness and the load on the legs. METHODS: Body mass, stature, and sitting height
      were directly measured and volumes and leg CSAs were obtained by 3D scanning for
      155 men and 162 women. Leg CSAs were regressed simultaneously on upper body mass
      and leg length. RESULTS: With allowance made for positive correlations with upper
      body mass, leg CSAs showed a negative correlation with leg length (P = 0.00006
      0.027). CONCLUSION: There is a negative correlation between leg lengths and CSAs
      that is largely obscured by other influences.

PMID- 22411044
TI  - Probabilistic learning from incomplete data for recognition of activities of
      daily living in smart homes.
AB  - Learning behavioral patterns for activities of daily living in a smart home
      environment can be challenged by the limited number of training data that may be
      available. This may be due to the infrequent repetition of routine activities
      (e.g., once daily), the expense of using observers to label activities, and the
      intrusion that would be caused by the presence of observers over long time
      periods. It is important, therefore, to make as much use of any labeled data that
      are collected, however, incomplete these data may be. In this paper, we propose
      an algorithm for learning behavioral patterns for multi-inhabitants living in a
      single smart home environment, by making full use of all limited labeled
      activities, including incomplete data resulting from unreliable low-level sensors
      in this environment. Through maximum-likelihood estimation, using Expectation
      Maximization, we build a model that captures both environmental uncertainties
      from sensor readings and user uncertainties, including variations in how
      individuals carry out activities. Our algorithm outperforms models that cannot
      handle data incompleteness, with increasing performance gains as incompleteness
      increases. The approach also enables the impact of particular sensors to be
      assessed and can thus inform sensor maintenance and deployment.

PMID- 22411045
TI  - Robust real-time-constrained estimation of respiratory motion for interventional
      MRI on mobile organs.
AB  - Real-time magnetic resonance imaging is a promising tool for image-guided
      interventions. For applications such as thermotherapy on moving organs, a precise
      image-based compensation of motion is required in real time to allow quantitative
      analysis, retrocontrol of the interventional device, or determination of the
      therapy endpoint. Reduced field-of-view imaging represents a promising way to
      improve spatial and/or temporal resolution. However, it introduces new challenges
      for target motion estimation, since structures near the target may appear
      transiently due to the respiratory motion and the limited spatial coverage. In
      this paper, a new image-based motion estimation method is proposed combining a
      global motion estimation with a novel optical flow approach extending the initial
      Horn and Schunck (H&S) method by an additional regularization term. This term
      integrates the displacement of physiological landmarks into the variational
      formulation of the optical flow problem. This allowed for a better control of the
      optical flow in presence of transient structures. The method was compared to the
      same registration pipeline employing the H&S approach on a synthetic dataset and
      in vivo image sequences. Compared to the H&S approach, a significant improvement
      (p<0.05) of the Dice's similarity criterion computed between the reference and
      the registered organ positions was achieved.

PMID- 22411046
TI  - Oxidative damage and antioxidant response of Allium cepa meristematic and
      elongation cells exposed to metronidazole.
AB  - The toxicity of metronidazole (MTZ) in meristematic and elongation zones of
      Allium cepa roots was analyzed for 30 h of exposition. Toxic effects were
      evaluated by lipid peroxidation (content of thiobarbituric-reactive substances
      [TBARS]), reduced glutathione (GSH) levels, ascorbate acid and dehydroascorbate
      acid content, and enzymatic activities of superoxide dismutase and catalase. The
      root zones showed differentiated susceptibility to MTZ. In the elongation zone,
      MTZ induced an increase of TBARS content and a significant rise in GSH levels,
      whereas in the meristematic zone, lipid peroxidation was not observed and all
      antioxidant defense parameters analyzed were significantly increased. These
      results indicate that MTZ exposure induced oxidative stress in A. cepa roots, and
      that the antioxidant defenses in the meristematic zone are more efficient
      compared with the elongation zone, which is probably related to higher oxidative
      metabolism of meristematic tissue.

PMID- 22411047
TI  - Inflammatory demyelinating CNS disorder in a case of X-linked Charcot-Marie-Tooth
      disease: positive response to natalizumab.

PMID- 22411048
TI  - LEV-zeotype magnesium aluminophosphates with variable Mg/Al ratios.
AB  - By using two different organic amines, n-methylpiperidine and 1,2
      diaminocyclohexane (DACH), as the structure-directing agents (SDAs), two
      magnesium aluminophosphate molecular sieves
      |(C(6)H(14)N)(2)|[Mg(2)Al(7)(PO(4))(9)] and
      |(C(6)H(14)N(2))(1.4)(H(2)O)(2)H(2)|[Mg(2)Al(5)(PO(4))(7)], denoted as MgAPO
      CJ67(a) and MgAPO-CJ67(b), have been synthesized under hydrothermal conditions.
      They are the first example of Mg incorporated aluminophosphates with the LEV
      zeotype structure. The magnesium and aluminum atoms co-occupy the same
      crystallographic positions in the frameworks of MgAPO-CJ67(a) and MgAPO-CJ67(b),
      but with different Mg/Al ratios of 1 : 3.5 and 1 : 2.5, respectively. MgAPO
      CJ67(a) exhibits higher thermal stability upon calcination than MgAPO-CJ67(b),
      and its framework keeps intact after the removal of occluded organic SDAs. The
      N(2) adsorption on the calcined MgAPO-CJ67(a) sample gives the BET surface area
      of 386 m(2) g(-1). NH(3)-temperature programmed desorption (NH(3)-TPD) analysis
      shows that MgAPO-CJ67(a) has a medium acidity.

PMID- 22411049
TI  - Improvement of growth and nitrogen utilization in sheep using sugar beet pulp
      treated with Trichoderma reesei or urea.
AB  - Twenty-five intact Barki lambs with mean body weight of 24.81 +/- 0.16 kg were
      used to investigate the effect of including in the diet sugar beet pulp (SBP)
      treated biologically with Trichoderma reesei or chemically with urea 4 % on
      nutrients digestibility, growth performance, nitrogen (N) utilization, and
      hematological and biochemical parameters. Two experiments were conducted. In the
      growth experiment, five lambs were randomly assigned to one of five dietary
      treatments. Lambs were offered isonitrogenous and isoenergetic concentrate feed
      mixture containing on dry matter basis 0 % SBP (D0), 50 % SBP (D1), 50 % SBP
      treated with 4 % urea (D2), 50 % SBP treated with T. reesei (D3), and 25 % SPB
      treated with 4 % urea plus 25 % SPB treated with T. reesei (D4). In the
      metabolism experiment, five rams were used in a 5 * 5 Latin square design and
      housed in metabolism crates for 21 days. The present study showed that inclusion
      of SBP at the level of 50 % (D1) negatively affected diet digestibility
      coefficients of crude protein, crude fiber, and ether extract, in addition to
      average daily gain, feed conversion, and N utilization. However, treatment of SBP
      with urea (D2), T. reesei (D3), or the combination (D4) of both had improved (P <
      0.05) these parameters with superiority of D3. Despite the significant
      differences in the tested hematological and biochemical parameters of lambs fed
      on biologically or chemically treated SBP diets, their levels remained within the
      physiological ranges which could indicate that treated SBP did not have any
      adverse effect on lambs' health.

PMID- 22411051
TI  - Viral load and acute otitis media development after human metapneumovirus upper
      respiratory tract infection.
AB  - The role of human metapneumovirus (hMPV) in acute otitis media complicating upper
      respiratory tract infection (URI) was studied. Nasopharyngeal specimens from 700
      URI episodes in 200 children were evaluated; 47 (7%) were positive for hMPV, 25
      (3.6%) with hMPV as the only virus. Overall, 24% of URI episodes with hMPV only
      were complicated by acute otitis media, which was the lowest rate compared with
      other respiratory viruses. hMPV viral load was significantly higher in children
      with fever, but there was no difference in viral load in children with hMPV
      positive URI with or without acute otitis media complication.

PMID- 22411052
TI  - Risk factors for diarrhea-associated infant mortality in the United States, 2005
      2007.
AB  - BACKGROUND: Diarrhea-associated deaths among US children increased from the mid
      1980s through 2006, particularly among infants. Understanding risk factors for
      diarrhea-associated death could improve prevention strategies. METHODS: Records
      of singleton infants with diarrhea listed anywhere on the death certificate were
      selected from the US Linked Birth/Infant Death data for the period, 2005 to 2007;
      characteristics of these infants were compared with those of infants who survived
      their first year. RESULTS: During 2005 to 2007, 1087 diarrhea-associated infant
      deaths were reported; 86% occurred among low birth weight (LBW, <2500 g) infants.
      Compared with normal birth weight (NBW, >=2500 g) infants, LBW infants had a
      greater mortality rate (risk ratio: 91.9, 95% confidence interval: 77.4-109.0)
      and younger median age at death (7 versus 15 weeks, P<0.0001). The most common
      codiagnoses for diarrhea-associated death among LBW and NBW infants were sepsis
      (26%) and volume depletion (20%), respectively. Among LBW infants, 97% of
      diarrhea-associated deaths occurred in inpatient settings, whereas 27% of NBW
      infant deaths occurred in outpatient settings and 5.3% in the decedent's home.
      Male sex, black race, unmarried status and low 5-minute Apgar score (<7)
      increased mortality odds among LBW infants whereas, among NBW infants, low 5
      minute Apgar score, black race, young maternal age (<25 years) and high birth
      order (third or more) increased mortality odds. CONCLUSIONS: Efforts to reduce
      diarrhea-associated morality should focus on understanding and improving
      management of diarrhea in vulnerable LBW infants. For prevention of diarrhea
      associated deaths in NBW infants, educating mothers who fit the high-risk profile
      regarding home hydration therapy and timely access to medical treatment is
      important.

PMID- 22411053
TI  - Impact of drug resistance on clinical outcome in children with tuberculous
      meningitis.
AB  - BACKGROUND: Tuberculous meningitis (TBM) is associated with delayed diagnosis and
      poor outcome in children. This study investigated the impact of drug resistance
      on clinical outcome in children with TBM. METHODS: All children (0-13 years) were
      included if admitted to Tygerberg Children's Hospital, Cape Town, South Africa,
      from January 2003 to April 2009 with a diagnosis of either confirmed TBM, or
      probable TBM with mycobacterial isolation from a site other than cerebrospinal
      fluid. Mycobacterial samples underwent drug susceptibility testing to rifampin
      and isoniazid. Children were treated with isoniazid, rifampin, pyrazinamide and
      ethionamide according to local guidelines. RESULTS: One hundred twenty-three
      children were included; 13% (16 of 123) had any form of drug resistance, and 4%
      (5 of 123) had multidrug-resistant tuberculosis. Time from start of symptoms to
      appropriate treatment was longer in children with any drug resistance (median: 31
      days versus 9 days; P=0.001). In multivariable analysis, young age (P=0.013) and
      multidrug-resistant tuberculosis (adjusted odds ratio: 12.4 [95% confidence
      interval: 1.17-132.3]; P=0.037) remained risk factors for unfavorable outcome,
      and multidrug-resistant tuberculosis remained a risk for death (adjusted odds
      ratio: 63.9 [95% confidence interval: 4.84-843.2]; P=0.002). We did not detect
      any difference in outcome between those with isolates resistant to only isoniazid
      and those with fully susceptible strains (adjusted odds ratio: 0.22 [confidence
      interval: 0.03-1.87]; P=0.17). CONCLUSION: Multidrug-resistant TBM in children
      has poor clinical outcome and is associated with death. We did not find any
      difference in the outcomes between children with isoniazid monoresistant TBM and
      those with drug-susceptible TBM. One explanation could be the local treatment
      regimen. Further investigation of this regimen is indicated.

PMID- 22411054
TI  - On-chip stochastic resonance of ion channel systems with variable internal noise.
AB  - We induced stochastic resonance in planar lipid bilayer systems with alamethicin
      ion channels, and varied alamethicin concentration, membrane area, and applied
      voltage. We found that membrane-induced microphonic noise significantly affects
      the signature of stochastic resonance, and that this noise can be used to
      optimize ion channel-based biosensors.

PMID- 22411055
TI  - Tissue culture system using a PANDA ring resonator and wavelength router for
      hydroponic plant.
AB  - A novel system of nanofluidics trapping and delivery, which is known as a tissue
      culture system is proposed. By using the intense optical pulse(i.e., a soliton
      pulse) and a system constructed by a liquid core waveguide, the optical vortices
      (gradient optical fields/wells) can be generated, where the trapping tools in the
      same way as the optical tweezers in the PANDA ring resonator can be formed. By
      controlling the suitable parameters, the intense optical vortices can be
      generated within the PANDA ring resonator, in which the nanofluidics can be
      trapped and moved (transported) dynamically within the Tissue culture system(a
      wavelength router), which can be used for tissue culture and delivery in the
      hydroponic plant system.

PMID- 22411056
TI  - Hybrid transistor manipulation controlled by light within a PANDA microring
      resonator.
AB  - In this paper, the novel type of transistor known as a hybrid transistor is
      proposed, in which all types of transistors can be formed by using a microring
      resonator called a PANDA microring resonator. In principle, such a transistor can
      be used to form for various transistor types by using the atom/molecule trapping
      tools, which is named by an optical tweezer, where in application all type of
      transistors, especially, molecule and photon transistors can be performed by
      using the trapping tools, which will be described in details.

PMID- 22411057
TI  - Organic farming benefits local plant diversity in vineyard farms located in
      intensive agricultural landscapes.
AB  - The majority of research on organic farming has considered arable and grassland
      farming systems in Central and Northern Europe, whilst only a few studies have
      been carried out in Mediterranean agro-systems, such as vineyards, despite their
      economic importance. The main aim of the study was to test whether organic
      farming enhances local plant species richness in both crop and non-crop areas of
      vineyard farms located in intensive conventional landscapes. Nine conventional
      and nine organic farms were selected in an intensively cultivated region (i.e. no
      gradient in landscape composition) in northern Italy. In each farm, vascular
      plants were sampled in one vineyard and in two non-crop linear habitats, grass
      strips and hedgerows, adjacent to vineyards and therefore potentially influenced
      by farming. We used linear mixed models to test the effect of farming, and
      species longevity (annual vs. perennial) separately for the three habitat types.
      In our intensive agricultural landscapes organic farming promoted local plant
      species richness in vineyard fields, and grassland strips while we found no
      effect for linear hedgerows. Differences in species richness were not associated
      to differences in species composition, indicating that similar plant communities
      were hosted in vineyard farms independently of the management type. This negative
      effect of conventional farming was probably due to the use of herbicides, while
      mechanical operations and mowing regime did not differ between organic and
      conventional farms. In grassland strips, and only marginally in vineyards, we
      found that the positive effect of organic farming was more pronounced for
      perennial than annual species.

PMID- 22411058
TI  - PKHD1 post-transcriptionally modulated by miR-365-1 inhibits cell-cell adhesion.
AB  - Autosomal recessive polycystic kidney disease (ARPKD) is a severe inherited
      disorder with an incidence of 1/20 000 live births. Mutations of PKHD1
      (polycystic kidney and hepatic disease gene 1) gene were identified to be
      responsible for ARPKD. However, the underlying molecular mechanisms remain
      largely unknown. MicroRNAs (miRNAs) are an abundant class of small RNAs with
      global effect on gene expression. Up to 30% of human protein coding genes may be
      regulated by miRNAs. However, to date, nothing is known regarding the role of
      miRNAs in PKHD1. In this study, we exploited bioinformatics to analyse the 3'UTR
      of PKHD1 gene and illustrated that the 3'UTR region of the gene is highly
      conserved in evolution. We identified about 35 candidate miRNAs within a 3738 bp
      window of the 3'UTR region. Of the 35 potential miRNAs, miR-365-1 emerged to post
      transcriptionally modulate the expression of PKHD1. Furthermore, we demonstrated
      that miR-365-1 modulated PKHD1 suppressed cell-cell adhesion in part through E
      cadherin.

PMID- 22411059
TI  - Children and adults exposed to low-frequency magnetic fields at the ICNIRP
      reference levels: theoretical assessment of the induced electric fields.
AB  - To avoid potentially adverse health effects, the International Commission on Non
      Ionizing Radiation Protection (ICNIRP) has defined reference levels for time
      varying magnetic fields. Restrictions on the electric fields induced in the human
      body are provided based on biological response data for peripheral nerve
      stimulation and the induction of phosphenes. Numerical modeling is commonly used
      to assess the induced electric fields for various exposure configurations. The
      objective of this study was to assess the variations of the electric fields
      induced in children and adults and to compare the exposure at reference levels
      with the basic restrictions as function of anatomy. We used the scalar potential
      finite element method to calculate the induced electric fields in six children
      and two adults when exposed to uniform magnetic fields polarized in three
      orthogonal directions. We found that the induced electric fields are within the
      ICNIRP basic restrictions in nearly all cases. In PNS tissues, we found electric
      fields up to 95% (upper uncertainty limit due to discretization errors, k = 2) of
      the ICNIRP basic restrictions for exposures at the general public reference
      levels. For occupational reference levels, we found an over-exposure of maximum
      79% (k = 2) in PNS tissues. We further found that the ICNIRP recommendations on
      spatial averaging in 2 * 2 * 2 mm3 contiguous tissue volumes and removal of peak
      values by the 99th percentile cause the results to depend strongly on the grid
      discretization step (i.e. an uncertainty of more than 50% at 2 mm) and the number
      of distinguished tissues in the anatomical models. The computational results
      obtained by various research institutes should be robust for different
      discretization settings and various anatomical models. Therefore, we recommend
      considering alternative routines for small anatomical structures such as non
      contiguous averaging without taking the 99th percentile in future guidelines
      leading to consistent suppression of peak values amongst different simulation
      settings and anatomical models. The peak electric fields depend on the local
      tissue distribution in the various anatomical models, and we could not find a
      correlation with the size of the anatomy. Therefore, we recommend extending the
      evaluation using a sufficient set of anatomies including other than standing
      postures to assess the worst-case exposure setting and correspondence to the
      basic restrictions.

PMID- 22411060
TI  - Early lung cancer detection using the self-evaluation scoring questionnaire and
      chest digital radiography: a 3-year follow-up study in China.
AB  - The standard definition of high-risk individuals for lung cancer was not uniform
      and the value of chest digital radiography (DR) in lung cancer screening was
      still unproven. The aim of this study was to assess whether the original
      questionnaire named as "Self-evaluation Scoring Questionnaire for High-risk
      Individuals of Lung Cancer" combined with DR examinations could detect early
      stage of lung cancer effectively. The Self-evaluation Scoring Questionnaire for
      High-risk Individuals of Lung Cancer had been designed in previous studies.
      Subjects with scores over 116 points were regarded as high-risk individuals and
      underwent the current DR scans at least once a year from 2007 to 2009.
      Noncalcified nodules with a diameter over 30 mm, along with enlarged pulmonary
      hilus and atelectasis, were considered to be positive and subjected to further
      special examinations. Efficacy of the scoring questionnaire combined with DR
      scans was estimated by 3-year results. Among 1,537 subjects, 13, 11, and 7 were
      diagnosed with lung cancer in the first, second, and third year, respectively,
      indicating the detection rate of 2.02 % (31/1,537). In addition, 77.42 % (24/31)
      of the patients were in stage I and 51.61 % (16/31) were adenocarcinomas. For the
      31 cases, 28 were defined as detected cancers, while the other three were
      interval ones, only accounting for 0.20 % (3/1,504) of individuals with negative
      judgments. The protocol of Self-evaluation Scoring Questionnaire for High-risk
      Individuals of Lung Cancer combined with DR scans is a cost-effective and safe
      approach to detect early stage of lung cancer.

PMID- 22411061
TI  - Leveraging Internet technologies with DICOM WADO.
AB  - The digital imaging and communications in medicine (DICOM) 3.0 standard was first
      officially ratified by the national electrical manufacturers association in 1993.
      The success of the DICOM open standard cannot be overstated in its ability to
      enable an explosion of innovation in the best of breed picture archiving and
      communication systems (PACS) industry. At the heart of the success of allowing
      interoperability between disparate systems have been three fundamental DICOM
      operations: C-MOVE, C-FIND, and C-STORE. DICOM C-MOVE oversees the transfer of
      DICOM Objects between two systems using C-STORE. DICOM C-FIND negotiates the
      ability to discover DICOM objects on another node. This paper will discuss the
      efforts within the DICOM standard to adapt this core functionality to Internet
      standards. These newer DICOM standards look to address the next generation of
      PACS challenges including highly distributed mobile acquisition systems and
      viewing platforms.

PMID- 22411062
TI  - Effect of xenon on excitatory and inhibitory transmission in rat spinal ventral
      horn neurons.
AB  - BACKGROUND: The minimum alveolar concentration is determined in the spinal cord
      rather than in the brain. Xenon inhibits glutamatergic excitatory synaptic
      transmission in the dorsal horn neurons. However, its actions in the ventral horn
      neurons have not been investigated. METHODS: The effects of 50 or 75% xenon on
      excitatory and inhibitory synaptic transmission were examined in the spinal
      lamina IX neurons of neonatal rats by using a whole cell patch clamp technique.
      RESULTS: Fifty percent xenon inhibited the alpha-amino-3-hydroxy-5-methyl-4
      isoxazole-4-propionic acid-induced currents (amplitudes = 72 +/- 9% and
      integrated area = 73 +/- 13% of the control values), and alpha-amino-3-hydroxy-5
      methyl-4-isoxazole-4-propionic acid receptor-mediated electrically evoked
      excitatory postsynaptic currents (amplitudes = 69 +/- 13% of the control values).
      Seventy-five percent xenon similarly inhibited alpha-amino-3-hydroxy-5-methyl-4
      isoxazole-4-propionic acid-induced currents. However, xenon had no effect on the
      N-methyl-D-aspartate-induced currents or N-methyl-D-aspartate receptor-mediated
      electrically evoked excitatory postsynaptic currents. Xenon decreased the
      amplitude, but not the frequency, of miniature excitatory postsynaptic currents.
      There were no discernible effects on the currents induced by gamma-aminobutyric
      acid or glycine or on miniature inhibitory postsynaptic currents. CONCLUSIONS:
      Xenon inhibits alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid
      receptor-mediated glutamatergic excitatory transmission in the spinal lamina IX
      neurons via a postsynaptic mechanism. In contrast, there are no substantial
      effects on N-methyl-D-aspartate receptor-mediated or inhibitory synaptic
      transmission. The suppressive effects on excitatory synaptic transmission in the
      ventral horn neurons partly account for the mechanism behind xenon's ability to
      produce immobility in response to noxious stimuli and to determine the minimum
      alveolar concentration.

PMID- 22411063
TI  - A 28-year-old man with air in the mediastinal space after a car accident.

PMID- 22411064
TI  - All in a Day's Work.

PMID- 22411065
TI  - Carrying on.

PMID- 22411066
TI  - Gastric tumor development in Smad3-deficient mice initiates from
      forestomach/glandular transition zone along the lesser curvature.
AB  - SMAD proteins are downstream effectors of the TGF-beta signaling pathway. Smad3
      null mice develop colorectal cancer by 6 months of age. In this study, we have
      examined whether the loss of Smad3 promotes gastric neoplasia in mice. The
      stomachs of Smad3-/- mice were compared with age-matched Smad3 heterozygous and
      wild-type mice. E-cadherin, Ki-67, phosphoSTAT3, and TFF2/SP expression was
      analyzed by immunohistochemisty. The short hairpin RNA (ShRNA)-mediated knockdown
      of Smad3 in AGS and MKN28 cells was also performed. In addition, we examined
      alterations in DCLK1-expressing cells. Smad3-/- mouse stomachs at 6 months of age
      revealed the presence of exophytic growths along the lesser curvature in the
      proximal fundus. Six-month-old Smad3-/- mouse stomachs showed metaplastic
      columnar glands initiating from the transition zone junction between the
      forestomach and the glandular epithelium along the lesser curvature. Ten-month
      old Smad3-/- mice all exhibited invasive gastric neoplastic changes with
      increased Ki-67, phosphoSTAT3 expression, and aberrant cytosolic E-cadherin
      staining in papillary glands within the invading submucosal gland. The shRNA
      mediated knockdown of Smad3 in AGS and MKN28 cells promoted the expression of
      phosphoSTAT3. DCLK1-expressing cells, which also stained for the tuft cell marker
      acetylated-alpha-tubulin, were observed in 10-month-old Smad3-/- mice within
      tumors and in fundic invasive lesions. In conclusion, Smad3-null mice develop
      gastric tumors in the fundus, which arise from the junction between the
      forestomach and the glandular epithelium and progress to prominent invasive
      tumors over time. Smad3-null mice represent a novel model of fundic gastric tumor
      initiated from forestomach/glandular transition zone along the lesser curvature.

PMID- 22411067
TI  - Caspase-1-mediated regulation of fibrogenesis in diet-induced steatohepatitis.
AB  - Non-alcoholic steatohepatitis (NASH) is typically associated with pro-apoptotic
      caspase activation. A potential role for pro-inflammatory caspases remains
      incompletely understood. Our aims were to examine a potential role of caspase-1
      in the development of liver damage and fibrosis in NASH. C57BL/6 wild type (WT)
      developed marked steatohepatitis, activation, fibrosis and increased hepatic
      caspase-1 and interleukin-1beta expression when placed on the methionine- and
      choline-deficient (MCD) diet. Marked caspase-1 activation was detected in the
      liver of MCD-fed mice. Hepatocyte and non-parenchymal fractionation of the livers
      further demonstrated that caspase-1 activation after MCD feeding was mainly
      localized to non-parenchymal cells. Caspase-1-knockout (Casp1(-/-)) mice on the
      MCD diet showed marked reduction in mRNA expression of genes involved in
      inflammation and fibrogenesis (tumor necrosis factor-alpha was 7.6-fold greater
      in WT vs Casp1(-/-) MCD-fed mice; F4/80 was 1.5-fold greater in WT vs Casp1(-/-)
      MCD-fed mice; alpha-smooth muscle actin was 3.2-fold greater in WT vs Casp1(-/-)
      MCD-fed mice; collagen 1-alpha was 7.6-fold greater in WT vs Casp1(-/-) MCD-fed
      mice; transforming growth factor-beta was 2.4-fold greater in WT vs Casp1(-/-)
      MCD-fed mice; cysteine- and glycine-rich protein 2 was 3.2-fold greater in WT vs
      Casp1(-/-) MCD-fed mice). Furthermore, Sirius red staining for hepatic collagen
      deposition was significantly reduced in Casp1(-/-) MCD-fed mice compared with WT
      MCD-fed animals. However, serum alanine aminotransferase levels, caspase-3
      activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling
      positive cells were similar in Casp1(-/-) and WT mice on the MCD diet. Selective
      Kupffer cell depletion by clodronate injection markedly suppressed MCD-induced
      caspase-1 activation and protected mice from fibrogenesis and fibrosis associated
      with this diet. The conclusion of this study is that it uncovers a novel role for
      caspase-1 in inflammation and fibrosis during NASH development.

PMID- 22411068
TI  - FOSL1 as a candidate target gene for 11q12 rearrangements in desmoplastic
      fibroblastoma.
AB  - Desmoplastic fibroblastoma (DF) is a benign fibroblastic/myofibroblastic tumor.
      Cytogenetic analyses have revealed consistent rearrangement of chromosome band
      11q12, strongly suggesting that this region harbors a gene of pathogenetic
      importance. To identify the target gene of the 11q12 rearrangements, we analyzed
      six cases diagnosed as DF using chromosome banding, fluorescence in situ
      hybridization (FISH), single-nucleotide polymorphism array and gene expression
      approaches. Different structural rearrangements involving 11q12 were found in
      five of the six cases. Metaphase FISH analyses in two of them mapped the 11q12
      breakpoints to an ~20-kb region, harboring FOSL1. Global gene expression
      profiling followed by quantitative real-time PCR showed that FOSL1 was expressed
      at higher levels in DF with 11q12 rearrangements than in desmoid-type
      fibromatoses. Furthermore, FOSL1 was not upregulated in the single case of DF
      that did not show cytogenetic involvement of 11q12; instead this tumor was found
      to display a hemizygous loss on 5q, including the APC (adenomatous polyposis
      coli) locus, raising the possibility that it actually was a misdiagnosed Gardner
      fibroma. 5'RACE-PCR in two 11q12-positive DF did not identify any fusion
      transcripts. Thus, in agreement with the finding at chromosome banding analysis
      that varying translocation partners are involved in the 11q12 rearrangement, the
      molecular data suggest that the functional outcome of the 11q12 rearrangements is
      deregulated expression of FOSL1.

PMID- 22411069
TI  - Changes in tympanic temperature during the exposure to electromagnetic fields
      emitted by mobile phone.
AB  - OBJECTIVE: Mobile phones generate microwave radiation which is absorbed by
      exposed tissue and converted into heat. It may cause detrimental health effects.
      The aim of the experiment was to check if exposure to EMF emitted by mobile phone
      influenced the tympanic temperature. MATERIAL AND METHODS: Human volunteer study
      was performed on ten healthy young men, aged 22.1+/-4.7 years, examined three
      times: 1. on a day with 2*60 min of no exposure (sham day), 2. on a day with
      continuous, 60 min exposure and 60 min of no exposure, 3. on a day with
      intermittent exposure (4*15 min "on" and 4*15 min "off"). Exposure was generated
      by mobile phone (frequency 900 MHz, SAR 1.23 W/kg). The study was double-blind,
      performed under controlled conditions (at 24 degrees C and 70% humidity). The
      tympanic temperature (T(ty)) was monitored every 10 sec by a thermistor probe
      placed close to the aural canal membrane in the ear opposite the one in contact
      with mobile phone (contralateral position). Multivariate repeated-measures
      analysis of variance was used to calculate the results. RESULTS: The mean T(ty)
      in the whole group during continuous exposure was significantly higher than
      during sham exposure (p = 0.0001). During intermittent exposure the temperature
      was lower than during sham day (difference was up to 0.11 degrees C). Within an
      hour after continuous exposure, T(ty) was higher by 0.03 degrees C and after
      intermittent exposure T(ty) was lower by 0.18 degrees C in comparison with sham
      day. Two hours after exposure T(ty) was significantly lower (p = 0.0001) than
      after sham exposure (0.06 degrees C and 0.26 degrees C respectively). The trends
      in T(ty) during experiment differed significantly in relation to exposure
      conditions (p < 0.05). CONCLUSIONS: The results of this analysis indicate that
      the physiological response to EMF exposure from mobile phone was mostly related
      to type of exposure (continuous or intermittent).

PMID- 22411070
TI  - Cancer incidence in Czech black coal miners in association with coalworkers'
      pneumoconiosis.
AB  - OBJECTIVE: The aim of the study was comparison of cancer incidence risk of lungs,
      stomach, colon, bladder and kidneys from ex-miners of black coal mines and the
      general male population of the Czech Republic. MATERIALS AND METHODS: The
      analysis was conducted in two cohorts of ex-miners according to the presence of
      coalworkers' pneumoconiosis (CWP). The first cohort included the miners without
      CWP (N = 6705), and the second cohort included the miners who were compensated
      for CWP (N = 2158). Personal and occupational data was merged with the data in
      the National Population Register and the National Oncological Register for the
      period from 1992 to 2006. Cancer risk in miners in comparison to the general male
      population of the Czech Republic was evaluated by SIR (Standardized Incidence
      Ratio) and 95% confidence interval (CI). RESULTS: About twice as high risk of
      lung cancer was found in miners with CWP (SIR = 2.21; 95% CI: 1.75-2.76). Lung
      cancer risk correlated with the severity of CWP (simple CWP SIR=1.96; 95% CI:
      1.48-2.56, progressive massive fibrosis SIR = 4.29; 95% CI: 2.09-7.87). No
      increased risk of lung cancer was found in ex-miners without CWP. The risk of
      malignant neoplasm at the other selected sites was comparable with the risk in
      the general male population of the Czech Republic. CONCLUSIONS: This study found
      increased lung cancer risk in coal miners with CWP, but not in those without CWP,
      comparing with the general population. These results served as the basis for the
      inclusion of lung cancer in association with CWP into a new Czech list of
      occupational diseases.

PMID- 22411071
TI  - The effect of exposure route on the distribution and excretion of
      hexachloronaphthalene in rats.
AB  - OBJECTIVES: Polychlorinated naphthalenes (PCNs), like other persistent organic
      pollutants (POPs), are widespread, global environmental contaminants. These
      compounds still represent a great environmental problem, mostly because of the
      risk of secondary air pollution. They are characterized by long durability and
      tendency to bioaccumulate, which means that they are practically ubiquitous in
      all environmental media and ecosystems. The aim of this study was to investigate
      the distribution and excretion of hexachloronaphthalene (HxCN) in rats following
      a single intraperitoneal or intragastrical administration. MATERIALS AND METHODS:
      Experiments were performed on male outbred Wistar rats with body weight of 220
      240 g. They were given [(14)C]-HxCN intraperitoneally (i.p.) or intragastrically
      (p.o.) in a single dose of 0.3 mg (150 kBq) per rat. The distribution of
      radioactivity in blood and selected organs or tissues, as well as urine and
      faeces excretion were traced following the administration. RESULTS: The decline
      of [(14)C]-HxCN in plasma was biphasic and the calculated half-lives for phases I
      and II were ~6 and 350 h, respectively. Following 120 h after administration,
      ~51% (intragastrical) and ~34% (intraperitoneal) of the dose were excreted with
      faeces. Regardless of the administration route, the highest HxCN concentrations
      were found in liver and adipose tissue, where the compound showed high retention:
      the highest retention in liver was found 24 h after intragastrical (32%) and
      intraperitoneal (38%) administration while in adipose tissue ~30% retention was
      observed 120 h after HxCN administration regardless of its route. CONCLUSIONS:
      Following the calculation of the balance of total [(14)C]-HxCN excreted and
      stored, it was found that hexachloronaphthalene belongs to the compounds of a
      slow turnover rate, and in the case of repeated exposure it may accumulate in the
      rat body.

PMID- 22411072
TI  - Medical thermography: a diagnostic approach for type 2 diabetes based on non
      contact infrared thermal imaging.
AB  - To test the potential of Infrared (IR) thermography in diagnosing as well as
      predicting type 2 diabetes and its complications compared with biochemical assay
      of HbA(1c) as standard. As per American Diabetes Association criteria, threshold
      for diagnosis of diabetes was set as HbA(1c) >= 6.5 % (7.7 mmol L-1). The total
      subjects (n = 62) were studied out of which control (n = 32) and diabetic
      subjects (n = 30). IR camera was used to capture the thermal images of the skin
      for diagnosis of the disease; receiver operating characteristic (ROC) curve was
      used to set temperature ( degrees C) as threshold for statistically significant
      body regions under t test. In diabetic group, HbA(1c) showed negative correlation
      with carotid region (r = -0.471, p < 0.01) and the mean skin temperature was
      lower than the normal group at body regions namely knee (p = 0.002), tibia (p =
      0.003), forehead (p = 0.014), and palm (p = 0.019). The palm region showed
      highest area under the curve of 0.711 (95% CI: 0.581-0.842) and the threshold was
      set as <=33.85  degrees C, thereby sensitivity (90%) and specificity (56%) was
      obtained in determining the undiagnosed diabetes with positive predictive value
      of 65%, negative predictive value of 85% and accuracy of 73%. As HbA(1c)
      increases, skin temperature decreases. Skin temperature enables early detection
      of diabetes as compared to HbA(1c). The decrease in skin temperature may be due
      to the decrease in the basal metabolic rate, poor blood perfusion and high
      insulin resistance. Thermography can be used as a diagnostic as well as
      prognostic tool for the diabetes.

PMID- 22411073
TI  - Light-driven chiral molecular switches or motors in liquid crystals.
AB  - The ability to tune molecular self-organization with an external stimulus is a
      main driving force in the bottom-up nanofabrication of molecular devices. Light
      driven chiral molecular switches or motors in liquid crystals that are capable of
      self-organizing into optically tunable helical superstructures undoubtedly
      represent a striking example, owing to their unique property of selective light
      reflection and which may lead to applications in the future. In this review, we
      focus on different classes of light-driven chiral molecular switches or motors in
      liquid crystal media for the induction and manipulation of photoresponsive
      cholesteric liquid crystal systems and their consequent applications. Moreover,
      the change of helical twisting powers of chiral dopants and their capability of
      helix inversion in the induced cholesteric phases are highlighted and discussed
      in the light of their molecular geometric changes.

PMID- 22411074
TI  - Dental health in Northern Chile's Atacama oases: evaluating the Middle Horizon
      (AD 500-1000) impact on local diet.
AB  - As one of the few areas apt for horticulture in Northern Chile's arid landscape,
      the prehistory of the Atacama oases is deeply enmeshed with that of the inter
      regional networks that promoted societal development in the south central Andes.
      During the Middle Horizon (AD 500-1000), local populations experienced a cultural
      apex associated with a substantial increase in inter-regional interaction,
      population density, and quantity and quality of mortuary assemblages. Here, we
      test if this cultural peak affected dietary practices equally among the distinct
      local groups of this period. We examine caries prevalence and the degree of
      occlusal wear in four series recovered from three cemeteries. Our results show a
      reduction in the prevalence of caries for males among an elite subsample from
      Solcor 3 and the later Coyo 3 cemeteries. Dental wear tends to increase over time
      with the Late Middle Horizon/Late Intermediate Period cemetery of Quitor 6
      showing a higher average degree of wear. When considered in concert with
      archaeological information, we concluded that the Middle Horizon was marked by
      dietary variability wherein some populations were able to obtain better access to
      protein sources (e.g., camelid meat). Not all members of Atacameno society
      benefited from this, as we note that this dietary change only affected men. Our
      results suggest that the benefits brought to the San Pedro oases during the
      Middle Horizon were not equally distributed among local groups and that social
      status, relationship to the Tiwanaku polity, and interment in particular
      cemeteries affected dietary composition.

PMID- 22411075
TI  - Gastric rupture with necrosis following acute gastric dilatation: report of a
      case.
AB  - Gastric rupture with necrosis following acute gastric dilatation (AGD) is a rare
      and potentially fatal event; usually seen in patients with eating disorders such
      as anorexia nervosa or bulimia. A 12-year-old lean boy with no remarkable medical
      history was brought to our Emergency Department suffering acute abdominal
      symptoms. Emergency laparotomy revealed massive gastric dilatation and partial
      necrosis, with rupture of the anterior wall of the fundus of the stomach. We
      performed partial gastrectomy and the patient recovered uneventfully. We report
      this case to demonstrate that AGD and subsequent gastric rupture can occur in
      patients without any underlying disorders and that just a low body mass index is
      a risk factor for this potentially fatal condition.

PMID- 22411076
TI  - Mechanistic insight on the catecholase activity of dinuclear copper complexes
      with distant metal centers.
AB  - The catecholase activity of two dinuclear Cu(II) complexes with distant metal
      centers is discussed together with solid state and solution studies. The crystal
      structure for one of them, [Cu(2)(diep)(H(2)O)(4)](ClO(4))(4).2H(2)O, is
      described, showing the two copper ions are 7.457 A apart and in a square
      pyramidal coordination. Both complexes display a weak antiferromagnetic coupling
      in the solid state that is manifest in the dimer EPR spectra obtained in frozen
      solution. The pH-potentiometric speciation performed in 1:1 MeOH-H(2)O allowed
      the assignment of hydrolyzed copper species as those catalytically active in the
      oxidation of 3,5-di-tert-butylcatechol (DTBC). The kinetic measurements led us to
      propose behavior consistent with Michaelis-Menten plus a linear dependence of the
      initial rate on [DTBC]. This can be associated with the presence of more than one
      catalytically active species, which is consistent with the evidence of several
      differently hydrolyzed species shown in the predominance diagrams. Product
      characterization studies led to establishing the formation of hydrogen peroxide
      during the catalytic cycle, while semiquinone and superoxide radicals were
      detected by EPR spectroscopy, supporting one-electron transference at each of the
      copper centers.

PMID- 22411077
TI  - Glycoside and peptide clustering around the octasilsesquioxane scaffold via
      photoinduced free-radical thiol-ene coupling. The observation of a striking
      glycoside cluster effect.
AB  - Two series of multivalent octasilsesquioxane glyco- and peptido-conjugates were
      synthesized using the photoinduced free-radical thiol-ene coupling (TEC). The
      first series was obtained by coupling C-glycosylpropyl thiols and cysteine
      containing peptides with the known octavinyl octasilsesquioxane while the second
      series was obtained by reacting glycosyl thiols with a new octasilsesquioxane
      derivative displaying eight PEGylated chains functionalized with terminal allyl
      groups. The evaluation of the binding properties of mannoside and glucoside
      clusters toward Concanavalin A by Enzyme-Linked Lectin Assay (ELLA) revealed a
      modest glycoside cluster effect. On the other hand, the PEGylated POSS-based
      glycocluster featuring eight N-acetyl-glucosamine residues showed high affinity
      toward Wheat Germ Agglutinin to give a measured IC(50) at 3 nM. The calculated
      relative potency per number of sugar unit (rp/n) was superior to a value of
      10(6), thus revealing the occurrence of a striking glycoside cluster effect.

PMID- 22411078
TI  - The role of therapeutic apheresis in the treatment of acute antibody-mediated
      kidney rejection.
AB  - Approximately 10% of renal transplant recipients experience acute antibody
      mediated rejection (AMR) due to alloimmunization against human leukocyte antigen
      (HLA) molecules and other antigens. While therapeutic apheresis is included in
      most treatment protocols for acute kidney allograft rejection, these protocols
      have been derived mainly from single center experience rather than controlled
      trials. This concise review focuses on the role of therapeutic apheresis in AMR
      treatment. Two groups have recently reported treating acute AMR using drug-only
      strategies without therapeutic apheresis in particular situations, namely in
      clinically less severe cases or in resource-limited situations without testing
      for donor specific antibodies. A randomized controlled trial, designed to test
      the efficacy of immunoadsorption apheresis in AMR treatment, was terminated early
      and suggested a benefit of apheresis. An observational study suggested efficacy
      of plasmapheresis in acute AMR treatment, but all patients who received
      plasmapheresis also received rituximab. As new therapeutic modalities are
      becoming available, therapeutic apheresis continues to play a role in the
      treatment of acute kidney allograft rejection.

PMID- 22411079
TI  - The switch of secondary sex determination in protandrous black porgy,
      Acanthopagrus schlegeli.
AB  - Hermaphrodites have both sexes during their life, including an initial primary
      sex determination and in later stage maintenance one of the sexual fates
      (secondary sex determination). Sex change (secondary sex determination) occurs in
      animals, but it is lost in amphibians through, mammals in vertebrates. Teleosts
      have various strategies and mechanisms of sex determination including genetic and
      environmental cues. However, the mechanisms by which the cues guide sex change
      are complicated in fish. This manuscript reviews our understanding of these
      processes in protandrous black porgy at the gonadal and neuroendocrine levels.
      Our studies addressed the process of sex change through brain-pituitary-gonad
      axis, and then secondary sex determination was switched by the fate of testis.

PMID- 22411080
TI  - Sensitivity and specificity of C-reactive protein and alpha(1) -acid glycoprotein
      for episodes of acute infection among children in Kilimanjaro, Tanzania.
AB  - OBJECTIVES: Biomarkers of inflammation, including C-reactive protein (CRP) and
      alpha(1) -acid glycoprotein (AGP), have tremendous potential in anthropological,
      public health, and nutrition research as objective indicators of acute infection;
      however, their usage is limited by the lack of widely agreed upon, reliable
      cutpoints to define infection. We assessed the sensitivity and specificity of CRP
      and AGP for identifying acute infectious disease (ID) episodes among children in
      the Kilimanjaro region of Tanzania. METHODS: Data were available from 43 3- to 5
      year-old children. CRP and AGP were measured in capillary whole dried blood spots
      (DBS). Two-week morbidity history interviews with children's primary caregivers
      were used to detect recent episodes of acute ID. Specimens and morbidity history
      interviews were collected from each child on one (n = 13) or two (n = 30)
      occasions for 73 paired interviews and specimens. RESULTS: We evaluated CRP and
      AGP for identifying acute infection (report of fever, diarrhea, or vomiting in
      the last week): CRP >= 1.1 mg/l had sensitivity of 57.14% and specificity of
      86.44%; AGP >= 0.76 g/l had sensitivity of 57.14% and specificity of 72.41%. The
      combined definition (AGP >= 0.76 g/l or CRP >= 1.1 mg/l) had sensitivity of
      71.43% and specificity of 70.69%. CONCLUSIONS: Among children in Kilimanjaro,
      Tanzania, assessed in whole blood stored as DBS, AGP >= 0.76 g/l or CRP >= 1.1
      mg/l provided the best definition of acute infection. Whether this definition is
      appropriate for use in other populations remains to be determined.

PMID- 22411081
TI  - Evidence-based physical therapy for BPPV using the International Classification
      of Functioning, Disability and Health model: a case report.
AB  - BACKGROUND AND PURPOSE: The model provided by the World Health Organization's
      International Classification of Functioning, Disability, and Health (ICF) was
      created to describe, classify, and measure function in both health care practice
      and research. This model has not been applied to management of many physical
      therapy cases, limiting its implementation conceptually into practice as a whole.
      The purpose of this case report is to illustrate the use of the ICF model in the
      evidence-based management of posterior canal benign paroxysmal positional
      vertigo. CASE DESCRIPTION: One patient with acute posterior canal canalithiasis
      benign paroxysmal positional vertigo was treated using the evidence-based
      clinical practice guideline for the diagnosis as well as the ICF framework.
      INTERVENTIONS: Repositioning maneuvers and education were provided to ameliorate
      the relevant body structure and function impairments, activity limitations, and
      contextual factors related to the patient's overall functioning and disability.
      OUTCOMES: The patient demonstrated complete abolishment of her symptoms, both
      objectively and subjectively after 3 sessions over 4 weeks of care. DISCUSSION:
      The physical therapy community has adopted the framework of the ICF because this
      model has been found to be effective in illustrating the impact of a patient's
      functional impairments in terms of activity limitations as well as the role that
      personal and environmental factors play in the patient's overall functioning and
      disability. When using the ICF in tandem with evidence-based care, patient
      outcomes have the capability to improve at an even greater rate; however, further
      research should be completed to discover this potential effect with appropriately
      designed clinical trials.

PMID- 22411082
TI  - Primary blast injuries--an updated concise review.
AB  - Blast injuries have been increasing in the civilian setting and clinicians need
      to understand the spectrum of injury and management strategies. Multisystem
      trauma associated with combined blunt and penetrating injuries is the rule.
      Explosions in closed spaces increase the likelihood of primary blast injury.
      Rupture of tympanic membranes is an inaccurate marker for severe primary blast
      injury. Blast lung injury manifests early and should be managed with lung
      protective ventilation. Blast brain injury is more common than previously
      appreciated.

PMID- 22411083
TI  - Adrenalectomy improves outcomes of selected patients with metastatic carcinoma.
AB  - BACKGROUND: Indications and survival benefit for adrenalectomy (ADX) in the
      setting of metastasis are not clearly defined. We aimed to determine which
      patients with primary malignancies may benefit from ADX performed for metastasis.
      Mayo Clinic institutional outcomes in patients with metastatic disease to the
      adrenal(s) treated by adrenalectomy were compared to stage-matched historical
      controls from the Surveillance Epidemiology and End Results (SEER) database.
      METHODS: A retrospective review (1992-2010) was conducted to identify patients
      treated with ADX for metastatic cancer at Mayo Clinic, Rochester. Associations of
      clinical, surgical, and pathologic features with overall survival (OS) were
      evaluated using Cox proportional regression models. OS for those treated with ADX
      was compared with that for SEER database stage-matched patients who underwent
      primary resection without resection of distant disease using log-rank tests.
      RESULTS: A total of 166 patients underwent ADX for metastatic primaries involving
      the kidney 60, lung 24, sarcoma 19, colon 15, pancreas 13, and other-35. Patients
      with sarcoma and kidney, lung, and pancreatic tumors who underwent ADX had better
      OS at 1, 2, and 3 years than did the SEER-matched controls. Respectively, the
      rates were for sarcoma (100, 93, 86% vs. 57, 36, 30%), kidney (86, 80, 72% vs.
      55, 37, 27%), lung (91, 69, 52% vs. 52, 34, 25%), and pancreas (79, 56, 45% vs.
      33, 20, 12%). Univariate analysis identified primary diagnosis <2 years before
      ADX, other distant site, pancreatic primary, palliative operation, and persistent
      disease as risk factors for death. CONCLUSIONS: An aggressive surgical approach
      results in improved OS in patients with metastatic disease arising from soft
      tissues, kidney, lung, and pancreas. Other tumors may benefit, but larger study
      cohorts are needed for a meaningful comparison.

PMID- 22411084
TI  - Role of portal vein embolization in hepatocellular carcinoma management and its
      effect on recurrence: a case-control study.
AB  - BACKGROUND: Liver regeneration that occurs after portal vein embolization (PVE)
      may have adverse effects on the microscopic tumor foci in the residual liver mass
      in patients with hepatocellular carcinoma (HCC). METHODS: Fifty-four HCC patients
      with inadequate functional residual liver volume were offered PVE during a seven
      year period. Among them, 34 (63%) patients underwent curative resection. They
      were compared with a matched control group (n = 102) who underwent surgery
      without PVE. Postoperative complications, pattern of recurrence, and survival
      were compared between groups. RESULTS: In the PVE group, a pre-embolization
      functional residual liver volume of 23% (12-33.5%) improved to 34% (20-54%) (p =
      0.005) at the time of surgery. When the two groups were compared, minor (PVE,
      24%; control, 29%; p = 0.651) and major (PVE, 18%; control, 15%; p = 0.784)
      complications were similar. After a follow-up period of 35 months (standard
      deviation 25 months), extrahepatic recurrences were detected in 10 PVE patients
      (29%) and 41 control patients (40%) (p = 0.310). Intrahepatic recurrences were
      seen in 10 (29%) and 47 (46%) cases (p = 0.109) in the PVE and control groups,
      respectively. In the PVE group, 41% (n = 14) of the recurrences were detected
      before one year, compared with 42% (n = 43) in the control group (p = 1). Disease
      free survival rates at 1, 3, and 5 years were 57, 29, and 26% in the control
      group and 60, 42, and 42% in the PVE group (log-rank, p = 0.335). On multivariate
      analysis, PVE was not a factor affecting survival (p = 0.821). CONCLUSIONS:
      Portal vein embolization increases the resectability of initially unresectable
      HCC due to inadequate functional residual liver volume, and it has no deleterious
      oncological effect after major resection of HCC.

PMID- 22411085
TI  - Subcuticular absorbable suture with subcutaneous drainage system prevents
      incisional SSI after hepatectomy for hepatocellular carcinoma.
AB  - BACKGROUND: The effectiveness of subcuticular absorbable suture with subcutaneous
      drainage to decrease the risk of postoperative incisional surgical site infection
      (SSI) in hepatocellular carcinoma (HCC) patients was evaluated. METHODS: A total
      of 149 patients with HCC who underwent hepatectomy (Hx) were retrospectively
      investigated. Patients were divided into two groups: the patients with
      subcuticular suture combined with subcutaneous drainage (the drainage group; 61
      patients) and the patients with nylon suture without subcutaneous drainage (the
      nylon group; 88 patients). After the operations, the complication rate of
      postoperative incisional SSI was analyzed and compared between the two groups.
      RESULTS: In the drainage group the rate of incisional SSI was significantly lower
      compared to the nylon group: 14-3 % (p = 0.033), respectively. Patients with
      incisional SSI needed significantly longer postoperative hospital care than the
      patients without incisional SSI: 28 versus 15 days (p < 0.005). Multivariate
      analysis revealed that subcuticular absorbable suture with subcutaneous drainage
      significantly reduced the occurrence of incisional SSI (odds ratio; 0.15; p =
      0.034). CONCLUSIONS: We have demonstrated that the subcuticular suture with
      subcutaneous drainage is effective in preventing incisional SSI in patients
      undergoing Hx for HCC.

PMID- 22411086
TI  - Preoperative treatment does not improve the therapeutic results of abdominosacral
      amputation of the rectum.
AB  - BACKGROUND: This study reviewed the impact of preoperative
      chemoradiotherapy/short-term radiotherapy on abdominosacral amputations of the
      rectum (ASAR) for the treatment of low-rectum cancers in terms of postoperative
      morbidity, local recurrence rates, and survival. METHODS: A total of 198 patients
      with stage II and III tumors located within 6 cm of the anorectal junction
      underwent ASAR between 1998 and 2008 and were selected for further analysis.
      Patients were compared according to the following groups: those who had surgery
      only (Group A) and those who had preoperative chemoradiotherapy/short-term
      radiotherapy (Group B). RESULTS: There were 44 and 154 patients in Groups A and
      B, respectively, including 135 males. The median age of the subjects was 63 years
      (range = 35-88). The median follow-up period was 81 months (range = 23-138).
      Neither the local recurrence rates (6.8% in Group A vs. 4.6% in Group B, p =
      0.544) nor the 5-year relative survival rates (72.4% in Group A vs. 69.3% in
      Group B, p = 0.127) differed significantly between the groups. CONCLUSION:
      Preoperative therapy in low-rectum cancer does not improve the therapeutic
      results of ASAR.

PMID- 22411087
TI  - Prognostic factors assessed for 15,096 patients with colon cancer in stages I and
      II.
AB  - BACKGROUND: We focused on the risk factors for poor outcome after curative
      resection of a colon cancer in UICC stages I and II based on the data of the
      Germany-wide quality assurance study "colon/rectum cancer (primary tumor)." In
      some countries, all stage II colon cancer patients are encouraged to participate
      in a clinical trial. We feel that this approach is too broad. METHODS: Using the
      data of 15,096 patients operated on from January 1, 2000 to December 31, 2004,
      the following factors were analyzed with the Cox regression model: age,
      comorbidities, ASA score, gender, localization of the tumor (left colon vs. right
      colon), perioperative complications (yes/no), pT stage, grading (G1/G2 vs.
      G3/G4), L-status (lymph vessels invasion yes/no), and V-status (venous invasion
      yes/no). RESULTS: The probability of a local relapse in stages I and II was 1.5
      and 4.6%, respectively, or distant metastases 4.7 and 10.2%, respectively. Only
      pT stage [hazard ratio (HR) for pT1 = 1, pT2 = 1.821, pT3 = 2.735, and pT4 =
      5.881], L-status (HR for L1 = 1.393), age (HR per year = 1.021), as well as ASA
      score IV (HR = 4.536) had significant influence on tumor-free survival.
      CONCLUSIONS: Despite favorable prognosis and R0 resection, a small percentage of
      patients will still relapse. The most important risk factor comprising the tumor
      free survival is the pT stage followed by L-status and age. These results should
      be taken into consideration when determining the course for adjuvant
      chemotherapy, especially if the course includes the recommendation of clinical
      trial participation for stage II colon cancer patients after an R0 resection.

PMID- 22411088
TI  - Resection of pulmonary metastases from hepatocellular carcinoma following liver
      transplantation.
AB  - BACKGROUND: This study was intended to assess the effect of resection of
      pulmonary metastasis (PM) of hepatocellular carcinoma (HCC) after liver
      transplantation (LT). No effective treatment modality exists for PM-HCC, and
      little is known about the posttransplant outcomes of pulmonary metastasectomy
      (PMT). METHODS: Of 587 adult LT recipients diagnosed with HCC, 43 had PM-HCC. We
      retrospectively compared outcomes in 23 patients who underwent PMT and 20 who did
      not. PMT was precluded in ten patients in the non-PMT group by multiple (usually
      >= 5) lung nodules, in nine by lung nodules with concurrent or residual
      extrapulmonary metastasis, and in one by comorbidity. RESULTS: Of the 23 patients
      in the PMT group, 14 underwent a single session of PMT, 7 underwent 2 sessions
      each, and 2 underwent 3 sessions each, for a total of 34 sessions. There were no
      surgery-related deaths or complications. After first PMT, 41 nodules, each 0.2
      2.5 cm in diameter, were observed: 1-5 nodules per patient. Every available
      treatment was provided to patients with post-PMT recurrence and those in the non
      PMT group to control pulmonary and extrapulmonary metastases. Patient survival
      rates before PM diagnosis did not differ between the two groups (p = 0.141).
      However, 2 year post-PM survival rate was significantly greater in the PMT group
      (30.6% vs. 0%, p = 0.007), resulting in a significantly greater overall 5 year
      survival rate (44.7% vs. 12.8%, p = 0.017). Univariate analysis showed no risk
      factor significantly associated with patient survival after PMT. CONCLUSIONS: PMT
      should be performed for resectable PM-HCC because it may provide a chance of long
      term survival.

PMID- 22411089
TI  - Double omental flap reduced perianastomotic collections and relaparotomy rates
      after pancreaticoduodenectomy with pancreaticogastrostomy.
AB  - INTRODUCTION: In an attempt to reduce the perioperative morbidity after
      pancreaticoduodenectomy, the results of double omental flap (DOF) after
      pancreaticoduodenectomy (PD) with pancreaticogastrostomy (PG) were compared to a
      standard technique. METHODS: From January 2009 to December 2009, 61 patients
      underwent PD with PG for pancreatic adenocarcinoma in our department.
      Perioperative data were prospectively recorded, and postoperative outcome of
      patients who underwent or not a DOF (group DOF+ = 33 and group DOF- = 28,
      respectively) was analyzed. RESULTS: The overall postoperative mortality was 1.6
      % (n = 1). The overall postoperative morbidity rate was 27.8 % (n = 17). PF
      occurred in eight (13.1 %) patients and was grade A in six (9.8 %) patients.
      Clinically relevant PF (grade B and C) occurred in two (3.2 %) patients. The
      univariate analysis showed that in the DOF+ groups there was a significant
      reduction of perianastomotic collections (P = 0.034) and a significant reduction
      of the relaparotomy rate (P = 0.05). DISCUSSION: The DOF contributed to reduce
      the rate of perianastomotic collections as well as the rate of relaparotomy.
      CONCLUSIONS: A DOF should be considered a further step toward a reduction of
      surgical-related complications after PD with PG.

PMID- 22411090
TI  - Intraoperative neuromonitoring does not reduce the incidence of recurrent
      laryngeal nerve palsy in thyroid reoperations: results of a retrospective
      comparative analysis.
AB  - PURPOSE: Recurrent laryngeal nerve (RLN) palsy is the major concern of
      reoperative thyroid surgery, and the introduction of neuromonitoring could reduce
      the rate of this complication. The present study is a retrospective analysis of
      the experience with completion thyroidectomy with and without neuromonitoring in
      a referral center. METHODS: Between October 1999 and April 2011, 246 patients [37
      men, 209 women; mean age, 55 +/- 12.5 (range, 25-80) years] underwent 250
      reoperations for recurrent goiter (n = 203), hyperthyroidism (n = 26), or
      recurrent thyroid cancer (n = 17). The mean interval between the initial and the
      reoperative procedure was 17.5 years. According to the availability of the
      neuromonitoring system and to the surgeon preference, 91 operations were
      performed with neuromonitoring (NM-group), whereas 159 were performed with direct
      nerve visualization (NV-group) alone. Patients' characteristics, perioperative
      data, and postoperative complications were collected in a prospectively
      maintained database. RESULTS: In the NM-group, 51 unilateral and 40 bilateral
      resections were performed. The NV-group included 122 unilateral and 37 bilateral
      procedures. The number of nerves at risk after previous surgery was 128 (NM
      group) and 161 (NV-group), respectively. We registered eight RLN palsy in the NM
      group (6.2 %) and four in the NV-group (2.5 %; p = 0.1). CONCLUSIONS: The routine
      use of intraoperative neuromonitoring seems not to reduce the incidence of RLN
      during redo thyroid surgery, at least in the setting of a tertiary referral
      center.

PMID- 22411091
TI  - Laparoscopic appendectomy outcomes on the weekend and during the week are no
      different: a national study of 151,774 patients.
AB  - BACKGROUND: The "weekend effect" is defined as increased morbidity and mortality
      for patients admitted on weekends compared with weekdays. It has been observed
      for several diseases, including myocardial infarction and renal insufficiency;
      however, it has not yet been investigated for laparoscopic appendectomy in acute
      appendicitis-one of the most prevalent surgical diagnoses. METHODS: The present
      study is based on the Nationwide Inpatient Sample (NIS) from 1999 to 2008. The
      following outcomes were compared between patients undergoing laparoscopic
      appendectomy for acute appendicitis admitted on weekdays versus weekends:
      severity of appendicitis, intraoperative and postoperative complications,
      conversion rate, in-hospital mortality, and length of hospital stay. Unadjusted
      and risk-adjusted generalized linear regression analyses were performed. RESULTS:
      Overall, 151,774 patients were included, mean age was 39.6 years, 52.6% (n =
      79,801) were male, and 25.3% (n = 38,317) were admitted on weekends. After risk
      adjustment, the conversion rate was lower [odds ratio (OR): 0.94, p = 0.004,
      number needed to harm (NNH): 244], whereas pulmonary complications (OR: 1.12, p =
      0.028, NNH: 649) and reoperations (OR: 1.21, p = 0.013, NNH: 1,028) were slightly
      higher on weekends than on weekdays. Overall postoperative complications (OR:
      1.03, p = 0.24), mortality (OR: 1.37, p = 0.075) and length of hospital stay
      (mean on weekday: 2.00 days, weekends: 2.01 days, p = 0.29) were not
      statistically different. CONCLUSIONS: The present investigation provides evidence
      that no clinically significant "weekend effect" for patients undergoing
      laparoscopic appendectomy exists. Therefore, hospital or staffing policy changes
      are not justified based on the findings from this large national study.

PMID- 22411092
TI  - Clinical features, treatment, and long-term outcome of papillary thyroid cancer
      in children and adolescents without radiation exposure.
AB  - BACKGROUND: Cancer of the thyroid gland is rare in children and adolescents. A
      history of neck irradiation is a well-established risk factor for tumor
      development, and most previous reports focused on cases that were induced by
      radiation exposure. We present here a retrospective review of the clinical
      features, treatment, and long-term outcome of children and adolescents with
      papillary thyroid cancer (PTC) without a history of radiation exposure who were
      treated at our institution over a period of ~50 years. METHODS: We
      retrospectively investigated 142 PTC patients without an irradiation history who
      were younger than 20 years of age when treated from 1961 to 2005 (17 males and
      125 females; mean age = 16.3 +/- 2.7 years; follow-up = 21.8 +/- 12.0 years). The
      clinicopathological results were evaluated using the medical records. Disease
      free survival (DFS) and cause-specific survival (CSS) were assessed with the
      Kaplan-Meier method and compared with the log-rank test. Parametric analyses were
      performed using Student's t test and nonparametric analyses were performed using
      the Mann-Whitney U test. RESULTS: At diagnosis, three patients had distant lung
      metastasis and 33 had gross neck lymph node (LN) metastasis. All patients were
      treated with surgery (hemi/partial thyroidectomy in 45 patients, subtotal
      thyroidectomy in 85, total thyroidectomy in 12, no LN dissection in 50, central
      compartment dissection in 20, and modified radical neck dissection in 72), and
      postoperative external beam radiation therapy was administered to 59.
      Postoperative ablative therapy using I(131) was not performed in this series.
      Recurrence was found for regional LN (n = 25), lung (n = 9), remnant thyroid (n =
      5), and others (n = 4). DFS and CSS at 40 years were 74.1 and 97.5%,
      respectively. DFS was significantly worse in patients aged <16 years with a
      family history of thyroid cancer, preoperative neck gross LN metastasis, maximum
      tumor diameter, and extrathyroidal invasion. Preoperative gross neck LN
      metastasis and distant metastasis at diagnosis were significant factors for CSS.
      No other factors contributed to DFS and CSS. When the clinical features of
      children and adolescents were compared, the incidence of preoperative gross neck
      LN metastasis and distant metastasis at diagnosis and tumors with a maximum
      diameter >10 mm were significantly higher in the children group than in the
      adolescent group. DFS was significantly shorter in the children group than in the
      adolescent group, but no significant difference was found in CSS between these
      two groups. CONCLUSIONS: The prognosis of PTC in children and adolescents is
      excellent, regardless of the extent of thyroidectomy and LN dissection. We
      recommend that only children or adolescents with preoperative gross neck LN
      metastasis and distant metastasis at diagnosis should be subjected to
      postoperative ablative therapy.

PMID- 22411093
TI  - Genetic structure and linkage disequilibrium in landrace populations of barley in
      Sardinia.
AB  - Multilocus digenic linkage disequilibria (LD) and their population structure were
      investigated in eleven landrace populations of barley (Hordeum vulgare ssp.
      vulgare L.) in Sardinia, using 134 dominant simple-sequence amplified
      polymorphism markers. The analysis of molecular variance for these markers
      indicated that the populations were partially differentiated (F(ST) = 0.18), and
      clustered into three geographic areas. Consistent with this population pattern,
      STRUCTURE analysis allocated individuals from a bulk of all populations into four
      genetic groups, and these groups also showed geographic patterns. In agreement
      with other molecular studies in barley, the general level of LD was low (13% of
      locus pairs, with P < 0.01) in the bulk of 337 lines, and decayed steeply with
      map distance between markers. The partitioning of multilocus associations into
      various components indicated that genetic drift and founder effects played a
      major role in determining the overall genetic makeup of the diversity in these
      landrace populations, but that epistatic homogenising or diversifying selection
      was also present. Notably, the variance of the disequilibrium component was
      relatively high, which implies caution in the pooling of barley lines for
      association studies. Finally, we compared the analyses of multilocus structure in
      barley landrace populations with parallel analyses in both composite crosses of
      barley on the one hand and in natural populations of wild barley on the other.
      Neither of these serves as suitable mimics of landraces in barley, which require
      their own study. Overall, the results suggest that these populations can be
      exploited for LD mapping if population structure is controlled.

PMID- 22411094
TI  - Pro-inflammation and pro-fibrosis factors were highly induction in heart tissues
      of carotid arteries balloon-injured animal model.
AB  - To investigate the changes of cardiomyocyte inflammation and fibrosis factors in
      heart of carotid artery balloon injury inflammatory rat model. Using rat carotid
      artery balloon injury model to detect left ventricular characteristics at 2 h, 2
      days and 14 days after surgery using hematoxylin-eosin (H&E) gross stain,
      Masson's trichome stain and Western blot analysis for inflammatory and fibrosis
      induced factors, tumour necrosis factor alpha (TNFalpha), JNK1, P38alpha,
      connective tissue growth factor (CTGF), SP1 and transforming growth factor beta
      (TGFbeta) protein expressions. The rat carotid arteries were injured after 2 h, 2
      days and 14 days. Balloon-angioplasty to H&E stain results showed the increasing
      trend of left ventricular wall at 2 h and 2 days; then, the left ventricular wall
      became thinner, and the left ventricular chamber became enlarged and dilated
      after 14 days of carotid artery balloon injury. In addition, the Masson's
      trichome stain results showed that the left ventricular section has fibrosis
      related blue staining (collagen) at 2 and 14 days after rat carotid artery
      balloon injury, and became even more severe at 14 days. Furthermore, we observed
      the protein expression level changs, which include TNFalpha, JNK1, P38alpha,
      CTGF, SP1 and TGFbeta using Western blotting assay. All proteins were induced at
      2 h, 2 days and then reached the maximal level at 14 days. The vessel
      inflammation was associated with cardiac inflammatory and fibrosis effects during
      or after carotid artery balloon injury.

PMID- 22411095
TI  - Functional and structural characterization of a thermostable acetyl esterase from
      Thermotoga maritima.
AB  - TM0077 from Thermotoga maritima is a member of the carbohydrate esterase family 7
      and is active on a variety of acetylated compounds, including cephalosporin C.
      TM0077 esterase activity is confined to short-chain acyl esters (C2-C3), and is
      optimal around 100 degrees C and pH 7.5. The positional specificity of TM0077 was
      investigated using 4-nitrophenyl-beta-D-xylopyranoside monoacetates as substrates
      in a beta-xylosidase-coupled assay. TM0077 hydrolyzes acetate at positions 2, 3,
      and 4 with equal efficiency. No activity was detected on xylan or acetylated
      xylan, which implies that TM0077 is an acetyl esterase and not an acetyl xylan
      esterase as currently annotated. Selenomethionine-substituted and native
      structures of TM0077 were determined at 2.1 and 2.5 A resolution, respectively,
      revealing a classic alpha/beta-hydrolase fold. TM0077 assembles into a doughnut
      shaped hexamer with small tunnels on either side leading to an inner cavity,
      which contains the six catalytic centers. Structures of TM0077 with covalently
      bound phenylmethylsulfonyl fluoride and paraoxon were determined to 2.4 and 2.1
      A, respectively, and confirmed that both inhibitors bind covalently to the
      catalytic serine (Ser188). Upon binding of inhibitor, the catalytic serine adopts
      an altered conformation, as observed in other esterase and lipases, and supports
      a previously proposed catalytic mechanism in which Ser hydroxyl rotation prevents
      reversal of the reaction and allows access of a water molecule for completion of
      the reaction.

PMID- 22411097
TI  - Beam quality corrections for parallel-plate ion chambers in electron reference
      dosimetry.
AB  - Current dosimetry protocols (AAPM, IAEA, IPEM, DIN) recommend parallel-plate
      ionization chambers for dose measurements in clinical electron beams. This study
      presents detailed Monte Carlo simulations of beam quality correction factors for
      four different types of parallel-plate chambers: NACP-02, Markus, Advanced Markus
      and Roos. These chambers differ in constructive details which should have notable
      impact on the resulting perturbation corrections, hence on the beam quality
      corrections. The results reveal deviations to the recommended beam quality
      corrections given in the IAEA TRS-398 protocol in the range of 0%-2% depending on
      energy and chamber type. For well-guarded chambers, these deviations could be
      traced back to a non-unity and energy-dependent wall perturbation correction. In
      the case of the guardless Markus chamber, a nearly energy-independent beam
      quality correction is resulting as the effects of wall and cavity perturbation
      compensate each other. For this chamber, the deviations to the recommended values
      are the largest and may exceed 2%. From calculations of type-B uncertainties
      including effects due to uncertainties of the underlying cross-sectional data as
      well as uncertainties due to the chamber material composition and chamber
      geometry, the overall uncertainty of calculated beam quality correction factors
      was estimated to be <0.7%. Due to different chamber positioning recommendations
      given in the national and international dosimetry protocols, an additional
      uncertainty in the range of 0.2%-0.6% is present. According to the IAEA TRS-398
      protocol, the uncertainty in clinical electron dosimetry using parallel-plate ion
      chambers is 1.7%. This study may help to reduce this uncertainty significantly.

PMID- 22411098
TI  - A randomized controlled trial comparing computer-aided learning with versus
      without tuition/lecture in promoting English proficiency.
AB  - AIM: To compare test scores in English-error detection between Thai high school
      students undergoing self-learning by an online tool (computer-assisted learning:
      CAL) with versus without tuition/lecture. METHODS: This prospective, randomized,
      controlled study enrolled a sample of grade-12 high school students from a Thai
      secondary school. The predictor variable was the use of error-detection exercises
      in 9 separate 50-min tuition sessions during a 3-week period. Each subject was
      randomly assigned to receive a CAL program with or without tuition/lecture during
      the study interval: June-September 2009. The main outcome variable was the test
      scores of English-error identification. To measure the outcomes, the students
      were evaluated twice using the 25-question test within a 1-month interval (pre
      test/post-test). Appropriate sample size estimates, descriptive, uni-, and
      bivariate statistics were calculated, and the level of statistical significance
      was set at P < 0.05. RESULTS: The sample included 69 students, 36 of whom (52.2%)
      were in the intervention group (CAL plus teaching). Within-group comparisons
      showed statistically significant improvements in post-test scores, regardless of
      learning methods (P < 0.05). Tuition/lecture was significantly associated with
      the improved post-test scores (P = 0.0012) and with a higher number of students
      showing improved post-test scores (P = 0.0007). CONCLUSIONS: The results of this
      study suggest that tuition/lecture facilitates self-learning with CAL. In this
      sample, tuition/lecture still seems to be necessary for nonnative-English
      speaking high school students to improve their English proficiency. CAL alone
      should not be used to replace conventional teaching.

PMID- 22411099
TI  - Selection and characterization of human respiratory syncytial virus escape
      mutants resistant to a polyclonal antiserum raised against the F protein.
AB  - A human respiratory syncytial virus (HRSV) neutralization escape mutant was
      obtained after 56 serial passages in the presence of a polyclonal antiserum
      raised against the F protein. Nucleotide sequence analysis of this escape mutant
      virus revealed two amino acid substitutions: Asn268Ile and Val533Met. When this
      virus was allowed to grow in the absence of the anti-F polyclonal serum, only the
      mutation Asn268Ile was stably maintained. Both the double and single escape
      mutant viruses lost reactivity with mAbs belonging to antigenic site II of the
      fusion protein of RSV. Mutation Asn268Ile has already been reported in RS viruses
      that are resistant to mAbs 47F and 11 and palivizumab (PZ). We have thus
      identified a novel mutation (Val533Met) in the transmembrane domain of the F
      protein that was selected under immune pressure.

PMID- 22411096
TI  - Activation and regulation of interferon-beta in immune responses.
AB  - Interferons (IFNs) were discovered more than half a century ago, and extensive
      research has since identified multifarious roles for type I IFN in human immune
      responses. Here, we review the functions of IFN-beta in innate and adaptive
      immunity. We also discuss the activation and influence of IFN-beta on myeloid
      cell types, including monocytes and dendritic cells, as well as address the
      effects of IFN-beta on T cells and B cells. Findings from our own laboratory,
      which explores the molecular mechanisms of IFN-beta activation by LPS and
      viruses, as well as from other groups investigating the regulation of IFN-beta by
      viral proteins and endogenous factors are described. The effects of post
      translational modifications of the interferon regulatory factor (IRF)-3 on IFN
      beta induction are also highlighted. Many unanswered questions remain concerning
      the regulation of the type I IFN response in inflammation, especially the role of
      transcription factors in the modulation of inflammatory gene expression, and
      these questions will form the basis for exciting avenues of future research.

PMID- 22411100
TI  - Identification of a novel subtype of South River virus (family Bunyaviridae).
AB  - We previously reported the isolation of South River virus (SORV) from a pool of
      mosquitoes collected in the Yucatan Peninsula of Mexico (Farfan-Ale et al. in
      Vector Borne Zoonotic Dis 10:777-783, 5). The isolate (designated SORV-252) was
      identified as SORV after a 197-nucleotide region of its small RNA genome segment
      was sequenced. In the present study, the complete small and medium RNA genome
      segments and part of the large RNA genome segment of SORV-252 were sequenced and
      shown to have 92%, 85% and 90% nucleotide sequence identity, respectively, to the
      homologous regions of the prototype SORV isolate (NJO-94F). To determine the
      antigenic relationship between SORV-252 and NJO-94F, cross-plaque reduction
      neutralization tests (PRNTs) were performed using sera from mice inoculated with
      these viruses. SORV-252 and NJO-94F were distinguishable in the cross
      neutralization assays; there was a twofold difference in the PRNT titers in one
      direction and a fourfold difference in the other direction, suggesting that SORV
      252 represents a novel subtype of SORV. Additionally, SORV-252 and NJO-94F have
      distinct plaque morphologies in African green monkey kidney (Vero) cells. In
      conclusion, we provide evidence that a novel subtype of SORV is present in the
      Yucatan Peninsula of Mexico.

PMID- 22411101
TI  - First histological and virological report of fibropapilloma associated with
      herpesvirus in Chelonia mydas at Principe Island, West Africa.
AB  - Marine turtle fibropapillomatosis is an emerging disease that affects marine
      turtles worldwide. This report describes the histopathological features and
      involvement of chelonid fibropapilloma-associated herpesvirus in marine turtle
      fibropapillomatosis detected in the green turtle Chelonia mydas at Principe
      Island, Gulf of Guinea. The histopathological findings confirmed the presence of
      fibropapillomas with both verrucous and fibromatous subtypes. Quantitative real
      time PCR was used for detection of chelonid fibropapilloma-associated herpesvirus
      in tissue samples (n = 18) collected from afflicted (n = 10) and apparently
      healthy turtles (n = 2), revealing 94.4% positive samples, confirming the
      presence of viral sequences not only in fibropapillomatosis lesions but also in
      the skin of apparently healthy animals.

PMID- 22411102
TI  - Biotransformation of clovane derivatives. Whole cell fungi mediated domino
      synthesis of rumphellclovane A.
AB  - Here we describe the biotransformation of clovane derivatives by filamentary
      fungi Pestalotiopsis palustris and Penicillium minioluteum, and the application
      of the latter to the synthesis and determination of the absolute configuration of
      rumphellclovane A (2). Methoxyclovanol (1), a growth inhibitor of the
      phytopathogen Botrytis cinerea, is metabolised by P. palustris to yield
      rumphellclovane A (2), a natural compound recently isolated from the gorgonian
      coral Rumphella antipathies, two new compounds, (1R,2S,5S,8R,9S,10R)-2
      methoxyclovane-9,10-diol (5) and (1S,2S,5S,7R,8R,9R)-2-methoxyclovane-7,9-diol
      (6), hydroxylated in positions not easily accessed by classic synthetic
      chemistry, and clovanodiols 3 and 4. P. minioluteum is able to selectively
      transform methoxyclovanol (1) into clovanodiols 3 and 4 and, in turn, lactone 8,
      the putative intermediate in the above mentioned synthesis of rumphellclovane A
      (2), into compound 2 via a domino process. The ability of P. minioluteum to carry
      out the cleavage of ethers on clovane derivatives is also evaluated.

PMID- 22411104
TI  - Daily aspirin reduces colorectal cancer incidence in patients with Lynch
      syndrome.

PMID- 22411103
TI  - Feedback-related brain activity predicts learning from feedback in multiple
      choice testing.
AB  - Different event-related potentials (ERPs) have been shown to correlate with
      learning from feedback in decision-making tasks and with learning in explicit
      memory tasks. In the present study, we investigated which ERPs predict learning
      from corrective feedback in a multiple-choice test, which combines elements from
      both paradigms. Participants worked through sets of multiple-choice items of a
      Swahili-German vocabulary task. Whereas the initial presentation of an item
      required the participants to guess the answer, corrective feedback could be used
      to learn the correct response. Initial analyses revealed that corrective feedback
      elicited components related to reinforcement learning (FRN), as well as to
      explicit memory processing (P300) and attention (early frontal positivity).
      However, only the P300 and early frontal positivity were positively correlated
      with successful learning from corrective feedback, whereas the FRN was even
      larger when learning failed. These results suggest that learning from corrective
      feedback crucially relies on explicit memory processing and attentional orienting
      to corrective feedback, rather than on reinforcement learning.

PMID- 22411105
TI  - Intra-genotypic variation of predominant genotype II strains of dengue type-3
      virus isolated during different epidemics in Thailand from 1973 to 2001.
AB  - The prevalence of all four dengue virus (DENV) serotypes has increased
      dramatically in recent years in many tropical and sub-tropical countries
      accompanied by an increase in genetic diversity within each serotype. This
      expansion in genetic diversity is expected to give rise to viruses with altered
      antigenicity, virulence, and transmissibility. We previously demonstrated the co
      circulation of multiple DENV genotypes in Thailand and identified a predominant
      genotype for each serotype. In this study, we performed a comparative analysis of
      the complete genomic sequences of 28 DENV-3 predominant genotype II strains
      previously collected during different DENV-3 epidemics in Thailand from 1973 to
      2001 with the goal to define mutations that might correlate with virulence,
      transmission frequency, and epidemiological impact. The results revealed (1) 37
      amino acid and six nucleotide substitutions adopted and fixed in the virus genome
      after their initial substitutions over nearly 30-year-sampling period, (2) the
      presence of more amino acid and nucleotide substitutions in recent virus isolates
      compared with earlier isolates, (3) six amino acid substitutions in capsid (C),
      pre-membrane (prM), envelope (E), and nonstructural (NS) proteins NS4B and NS5,
      which appeared to be associated with periods of high DENV-3 epidemic activity,
      (4) the highest degree of conservation in C, NS2B and the 5'-untranslated region
      (UTR), and (5) the highest percentage of amino acid substitutions in NS2A
      protein.

PMID- 22411106
TI  - Predicting Homo pigmentation phenotype through genomic data: from Neanderthal to
      James Watson.
AB  - BACKGROUND: Human pigmentation is regulated by several genes acting at different
      stages of melanin formation. Functional and association studies have elucidated
      the role of several of these genes in pigmentation phenotypes. Forensic and
      evolutionary studies can benefit from this knowledge. OBJECTIVES: To evaluate the
      reliability of the prediction of pigmentation phenotypes using a large database
      of genetic markers in individuals with known phenotypes; and from this try to
      predict the pigmentation phenotype of prehistoric Homo specimens and of
      contemporary individuals whose visible phenotypes are not known. METHODS: We
      compared predicted and observed phenotypic data through an analysis of 124 single
      nucleotide polymorphisms in 33 genic and seven intergenic regions of 30 subjects,
      five of them prehistoric, whose complete nuclear genomes are available in UCSC
      and PSU UCSC public databases. RESULTS: For the molecular predicted versus
      observed phenotypes, the percentage of agreement was as follows: freckles: 91;
      skin: 64; hair: 44; eyes: 36; total: 59; while the molecular predicted versus
      probable (no visible observation available; inferences based on ethnic population
      characteristics) it was, respectively, 83, 60, 42, 67, and 63. The difference
      between two sets is statistically nonsignificant (P = 0.75). CONCLUSION: To our
      knowledge, this is the first article to examine the effect of a large number of
      genetics markers for phenotype prediction. The approach could be useful for
      forensic applications, as well as for the determination of possible phenotypes of
      extinct prehistoric individuals.

PMID- 22411108
TI  - Cognitive behavior therapy after acquired brain injury:  maintenance of
      therapeutic benefits at 6 months posttreatment.
AB  - OBJECTIVES: To examine whether 6-month posttreatment acquired brain injury (ABI)
      patients receiving cognitive behavior therapy (CBT) adapted for ABI would
      demonstrate (1) maintenance of psychological benefits, (2) better community
      integration, and (3) commensurate benefits for both teletherapy and face-to-face
      group therapy. A secondary objective was to examine the relationship between
      coping strategies and mood and community integration. PARTICIPANTS: Seventeen
      chronic ABI patients with elevated psychological distress. OUTCOME MEASURES:
      Symptom Checklist-90-Revised (SCL-90-R), Depression Anxiety Stress Scales-21
      (DASS-21), Community Integration Questionnaire, and the Ways of Coping
      questionnaire, revised. PROCEDURES: Eleven CBT sessions provided either in a face
      to-face group format or individually by telephone with outcomes measured
      pretreatment, posttreatment, and at 6-month follow-up. RESULTS: At 6-month follow
      up, full-group scores were significantly better than pretreatment for
      psychological distress (t(16) = 6.22, P < .01, SCL-90-R; t(16) = 7.32, P < .01,
      DASS-21) and for community integration (t(16) = -6.15, P < .01), with negligible
      decrements from immediately posttreatment. Subgroup scores were comparable.
      Coping also improved but was uncorrelated with mood or community integration.
      CONCLUSION: The CBT adapted for ABI shows enduring benefits for mood and
      community integration. The efficacy of teletherapy obviates service access
      problems related to geographical remoteness and mobility restrictions. A larger,
      randomized, control trial that examines underlying mechanisms of efficacy is
      needed.

PMID- 22411107
TI  - Association of depressive symptoms with functional outcome after traumatic brain
      injury.
AB  - OBJECTIVE: To test whether improved functional status correlates with more
      depressive symptoms after traumatic brain injury (TBI). This is based on the
      concept that increasing awareness of deficits may exacerbate depression, even
      while survivors are making functional improvements. PARTICIPANTS: A total of 471
      individuals with TBI (72% white; 71% men; median Glasgow Coma Scale (GCS) score =
      11) enrolled during acute care or inpatient rehabilitation and followed up at a
      median of 6 months. MAIN MEASURE: Beck Depression Inventory-II (BDI-II), Glasgow
      Outcome Scale-Extended, and Functional Status Examination (FSE). RESULTS: We
      found significant Spearman rank order correlations between BDI-II scores and the
      total FSE as well as all domains of the FSE. Lower functional levels correlated
      with more depressive symptoms. Modeling of predictive factors, including subject
      characteristics, injury-related characteristics, and outcome measures, resulted
      in 2 models, both containing age and GCS along with other factors. CONCLUSION:
      The relation between depressive symptoms and functional outcomes is complex and a
      fertile area for further research. The authors would encourage clinicians to
      monitor patients for depressive symptoms to help to prevent the detrimental
      impact on recovery.

PMID- 22411109
TI  - Clinical utility of the protein S100B to evaluate traumatic brain injury in the
      presence of acute alcohol intoxication.
AB  - OBJECTIVE: To examine the role of the protein S100B as a biomarker for traumatic
      brain injury (TBI) in the presence of acute alcohol intoxication. PARTICIPANTS: A
      total of 159 patients who presented to a large urban level 1 trauma center in
      Vancouver, British Columbia, Canada, were included. Patients were classified into
      4 clinical groups-medical controls (MC), trauma controls (TC), uncomplicated mild
      TBI (MTBI), and definite TBI (DTBI)-and 2 day-of-injury alcohol intoxication
      groups (ie, sober and intoxicated). PROCEDURE: Blood samples were collected
      within 8 hours of injury. MAIN OUTCOME MEASURE: Protein S100B concentration
      (MUg/L; Sangtec 100 Elisa, DiaSorin, Stillwater, Minnesota). RESULTS: Higher
      S100B levels were found in patients who sustained a TBI than in those in the MC
      and TC groups (DTBI & MTBI >TC & MC). There was a positive linear relation
      between S100B levels and brain injury severity (DTBI > MTBI). Alcohol consumption
      at the time of injury did not generally affect S100B levels. The S100B levels had
      medium diagnostic accuracy for the majority of patients, with the exception of
      the DTBI-sober group in which S100B levels had very high diagnostic accuracy.
      CONCLUSION: Patients with uncomplicated MTBIs and DTBIs had much higher levels of
      S100B than MC and TC participants. This biomarker had medium diagnostic accuracy
      for detecting DTBI in the presence of alcohol intoxication and very high accuracy
      in sober patients.

PMID- 22411110
TI  - Isoguanine formation from adenine.
AB  - Several possible mechanisms underlying isoguanine formation when OH radical
      attacks the C(2) position of adenine (A C 2) are investigated theoretically for
      the first time. Two steps are involved in this process. In the first step, one of
      two low-lying A C 2???OH reactant complexes is formed, leading to C(2)-H(2) bond
      cleavage. Between the two reactant complexes there is a small isomerization
      barrier, which lies well below separated adenine plus OH radical. The complex
      dissociates to free molecular hydrogen and an isoguanine tautomer (isoG 1 or isoG
      2). The local and activation barriers for the two pathways are very similar. This
      evidence suggests that the two pathways are competitive. After dehydrogenation,
      there are two possible routes for the second step of the reaction. One is direct
      hydrogen transfer, via enol-keto tautomerization, which has high local barriers
      for both tautomers and is not favored. The other option is indirect hydrogen
      transfer involving microsolvation by one water molecule. The water lowers the
      reaction barrier by over 20 kcal  mol(-1) , indicating that water-mediated
      hydrogen transfer is much more favorable. Both A+OH(?) ->isoG+H(?) reactions are
      exothermic and spontaneous. Among four isoguanine tautomers, isoG 1 has the
      lowest energy. Our findings explain why only the N(1)H and O(2)H tautomers of
      isolated isoguanine and isoguanosine have been observed experimentally.

PMID- 22411111
TI  - Denervation of the distal interphalangeal joint.
AB  - Distal interphalangeal joint osteoarthritis is one of the most common conditions
      hand surgeons have to deal with. When daily manual activities are impaired by
      symptoms, surgical treatment is indicated. Usually, this is carried out by means
      of arthrodesis, being joint replacement another option. In this study, a
      technique for distal interphalangeal joint denervation is presented as a
      treatment for painful degenerative or posttraumatic osteoarthritis. Potential
      complications and contraindications are also discussed.

PMID- 22411112
TI  - Repair of collateral ligament ruptures in the metacarpophalangeal joints of the
      long fingers.
AB  - Isolated collateral ligament ruptures in the metacarpophalangeal joints of the
      fingers seem to be more frequent than described. For ligament repair, dorsal
      access is generally described, but the proper method by which to proceed inside
      the joint is unclear and left to the surgeon's discretion and experience. With
      the technique we propose, it is possible to explore the interior of the joint
      from the top, allowing an easy and complete examination of the entire length of
      the ligament. This proposed method allows for a better identification of the
      lesion and the area of ligament reinsertion, facilitating technical decision
      making, and reducing the operating time.

PMID- 22411113
TI  - The effect of conservative management in extensor plus finger after partial
      amputation to the ulnar digits--a case report.
AB  - The extensor plus finger after partial amputation of ulnar digits can affect the
      functions of the hand. The therapist intricate knowledge of intrinsic and
      extrinsic mechanism of fingers and creative approach in therapy would solve the
      puzzle when managing complex problem (extensor plus finger). Here we study a case
      of extensor plus finger after partial amputation of ulnar digits, its mechanism,
      and our experience with conservative management in managing extensor plus finger.

PMID- 22411114
TI  - Versatility of venous flap for coverage of proximal and middle phalanges of
      fingers.
AB  - Owing to paucity of soft tissue in the fingers, the trauma to fingers can cause
      exposure of tendons, joints, and bone. Several flaps have been used to cover soft
      tissue defects of the fingers. From 2007 to 2010, we have operated on 18 male
      patients with skin defects of dorsal phalanges of fingers. We used reverse
      distally based venous flap with perivenous tissue to cover the defects. Their
      mean age was 30.6+/-8.6 (15 to 40). The etiology in all cases was severe trauma.
      Ten had defect in dorsal aspect of proximal phalanges and in 8 the defect was in
      the middle phalanges. One of our patients experienced superficial necrosis at the
      distal margin of the flap that was successfully treated with local wound care and
      dressing changes. There was 1 case of venous congestion that resolved itself.
      There were no postoperative wound infections. There were no serious
      complications. The venous flap with preservation of perivenous areolar network is
      a good option for coverage of soft tissue defects of proximal and middle
      phalanges of fingers.

PMID- 22411115
TI  - A new technique of single portal endoscopic carpal tunnel release.
AB  - Since the first description of endoscopic carpal tunnel release (ECTR) in 1987 by
      Okutsu many endoscopic techniques have been developed, but the majority of the
      literature on ECTR has dealt with the Chow and Agee techniques. ECTR is indicated
      for carpal tunnel syndrome that is not responding to conservative treatment for 6
      months. This new technique of ECTR is a single-portal technique using instruments
      originally designed for endoscopic cubital tunnel release, with no disposable
      instruments used. It also has the advantage of performing the release with the
      median nerve protected under direct vision. Ten cases were operated with this
      technique after performing the procedure on 8 hands of 4 fresh frozen cadavers.
      There were no neurovascular or tendon injuries with this technique and patients
      were satisfied with the results.

PMID- 22411116
TI  - Dual-window subscapularis-sparing approach: a new surgical technique for combined
      reconstruction of a glenoid bone defect or bankart lesion associated with a HAGL
      lesion in anterior shoulder instability.
AB  - Combined bankart lesion and humeral avulsion of glenohumeral ligament lesion
      (HAGL) is a well-described pathologic complex in anterior shoulder instability;
      open surgical approaches with and without arthroscopic assistance have been
      suggested for simultaneous 1-stage repair of these lesions. Presence of a
      significant glenoid bone defect (inverted-pear glenoid) adds to the complexity of
      the problem and necessitates a bony reconstruction procedure. Open surgical
      approaches described for management of this combined lesion complex in anterior
      shoulder instability necessitate a subscapularis-cutting approach; suboptimal
      healing of the tenotomized subscapularis and subsequent delayed rehabilitation
      predisposes to late subscapularis dysfunction, and this compromises clinical
      outcomes. This study describes a new surgical technique that utilizes a dual
      window approach through the subscapularis muscle; the dual window enables access
      to the glenoid and humeral lesions without the need for a subscapularis tenotomy.
      The approach can be used to perform a congruent-arc Latarjet procedure (for
      glenoid bone defects) or a Bankart repair (for capsulolabral lesions), in
      combination with a HAGL repair. Preliminary arthroscopy is essential to identify
      significant bone defects and HAGL lesions. The dual-window approach for
      reconstruction of the lesions involves (1) a lateral "subscapularis-sparing"
      window to identify and repair the HAGL lesion; (2) a medial "subscapularis muscle
      splitting" window to perform either a glenoid capsulolabral reconstruction or a
      congruent-arc Latarjet procedure; and (3) a balanced inferior capsular shift and
      lateralization procedure of the glenohumeral capsule. Technical tips and
      guidelines to avoid complications are discussed, and a rehabilitation protocol is
      presented.

PMID- 22411117
TI  - A new single volar approach for epiphyseal ulnar and radial-sided comminutive
      fracture of the distal radius: the mediolateral windows approach.
AB  - Articular comminuted distal radius fractures are still a surgical challenge. The
      development of volar locking plate device allows a stable and anatomic
      restoration of the distal radius. We propose a modification of the classic
      anterior approach for articular fracture of the distal radius with ulnar
      impaction. By a single incision, we realize 2 windows to expose the medial and
      lateral column of the distal radius. This technique is indicated for complex
      articular distal radius fractures associated with an ulnar comminution. The
      dissection is extended superficially to the ulnar side of the carpal tunnel
      elements by a blunt dissection of the anterior part of the wrist between the skin
      and the superficial layer of the flexor carpi radialis, in subcutaneous tissues
      and the antebrachial fascia to preserve the sensitive branch of the median nerve.
      This new approach allows reduction of each fragment of a comminutive articular
      fracture without exposing the flexor tendon and median nerve to excessive
      tension. In our surgical armatorium, we reserved this technique for distal radius
      fractures with articular ulnar damage because of the possible risk to the median
      cutaneus branch.

PMID- 22411118
TI  - Modified bone tie:  a new method to achieve interfragmentary compression in
      unstable oblique metacarpal and phalangeal fractures.
AB  - Oblique fractures of the metacarpal and phalanx are inherently unstable
      especially when there is comminution at the fracture site. Nonoperative
      management of these fractures requires prolonged immobilization and results in
      poor outcome. Internal fixation is the preferred method of treatment for these
      fractures. The various methods used for internal fixation are the Kirschner
      wires, intraosseous wiring, tension band wiring, minifragment screws and plates.
      Kirschner wires are the most commonly used fixation device because of their
      versatility and easy availability. The main disadvantage is lack of rigid
      fixation as it does not provide interfragmentary compression and pin track
      infection, if left outside the skin. To overcome these problems intraosseous
      wiring and tension band wiring were used. The main disadvantage of these
      procedures is the need for multiple drilling and extensive soft tissue dissection
      which is detrimental for a comminuted oblique fracture. Minifragment screws and
      plates provide rigid fixation but the screw can split the small bone fragment and
      also does not allow any adjustment once it is inserted. Plates tend to be bulky.
      Bone tie was described as a method of interfragmentary compression with some
      advantages over the interosseous wiring techniques and tension band wiring. We
      have modified the original bone tie to make it easier to use and to provide more
      stable fixation. We present our experience with its use in unstable oblique
      fractures of the metacarpal and phalanges, which are challenging to treat.

PMID- 22411119
TI  - Flexor tendon retrieval in zone I and II: a new modified technique.
AB  - In this article we set out to describe a simple and modified Sourmelis technique
      for tendon retrieval in zone I and II. In this modified technique, a long loop of
      nylon suture is used and hence there is no need for the stage 4 of Sourmelis
      technique. The purpose of this paper is to illustrate this modification.

PMID- 22411120
TI  - Postoperative monitoring in free muscle transfers for reconstruction in brachial
      plexus injuries.
AB  - Free gracilis transfers are done for reanimation of the upper limb in traumatic
      total brachial plexus palsy. Because of buried nature of the free muscle and
      monitoring skin flap in the axillary or infraclavicular region, it is always a
      tricky situation for continuous and repeated monitoring to assess vascular
      status. Critical ischemia times vary between the muscle and monitoring skin flap
      because of which signs of ischemic changes in the monitoring skin flap are always
      delayed with respect to the muscle. We describe a novel method that uses the
      principle of evoked potentials from the muscle to assess the vascular status of
      the free muscle and detects vascular compromise early before the skin changes are
      apparent.

PMID- 22411121
TI  - Perineural fat grafting in the treatment of painful neuromas.
AB  - Treatment of painful neuromas of the upper limb has been largely debated. The
      current surgical treatments spare from simple neuroma excision to proximal nerve
      stump relocation (into muscles, veins, and bones). Perineural fat grafting
      consists of neuroma excision and the creation of an autologous adipose graft
      wrapped around the proximal nerve stump. This technique should be prescribed to
      those patients suffering from terminal neuromas or neuromas in which functional
      reconstruction is contraindicated. The effectiveness of this technique could be
      addressed both to the mechanical and biological properties of the fat graft. On
      one hand the graft creates a gliding layer and a protective barrier, thus
      allowing longitudinal excursion and protection against mechanical solicitations.
      On the other hand the autologous adipose tissue brings neoangiogenesis, modulates
      the inflammatory response, and avoids scar adherences. A retrospective analysis
      was performed on 7 neuromas in 7 patients, treated with perineural fat grafting
      from June 2009 to February 2010. Pain and limb functionality were measured,
      respectively, with a visual acuity scale and the "Disabilities of the Arm,
      Shoulder, and Hand score," preoperatively and 1 year after surgery. A mean pain
      reduction of 23% was recorded, without relevant complications. Improvements in
      limb functionality were also observed through the measurement of the Disabilities
      of the Arm, Shoulder, and Hand score, which improved to 18%. We believe that this
      technique represents a valuable and versatile option in the treatment of painful
      neuromas of the upper limb that could be hereafter performed for pain syndromes
      of neuropatic origin.

PMID- 22411122
TI  - Orthogonal biplanar fluoroscopy-guided percutaneous fixation of a coracoid base
      fracture associated with acromioclavicular joint dislocation.
AB  - Coracoid process fractures that involve the coracoid base (inferior pillar)
      without a concomitant rupture of the coracoclavicular ligaments can destabilize
      the acromioclavicular joint with its subsequent dislocation; prophylactic or
      therapeutic operative treatment involving open reduction and internal fixation
      has been traditionally recommended. This report presents a new technique of
      percutaneous reduction and stabilization of the coracoid fracture with indirect
      acromioclavicular joint reduction under fluoroscopic guidance; biplanar
      visualization of coracoid process anatomy is obtained using 2 specific
      radiographic/fluoroscopic-beam angulations (Bhatia views), and this permits a
      guided placement of screws for controlled reduction of this dual injury. The
      technique is based on the author's original work on coracoid process anatomy and
      development of radiographic views for orthogonal visualization of coracoid
      pillars in their entirety. Technical tips to facilitate percutaneous fracture
      fixation and to avoid potential complications are discussed.

PMID- 22411123
TI  - Gene expression signatures of pediatric myelodysplastic syndromes are associated
      with risk of evolution into acute myeloid leukemia.

PMID- 22411124
TI  - Spatial correspondence of 4D CT ventilation and SPECT pulmonary perfusion defects
      in patients with malignant airway stenosis.
AB  - To determine the spatial overlap agreement between four-dimensional computed
      tomography (4D CT) ventilation and single photon emission computed tomography
      (SPECT) perfusion hypo-functioning pulmonary defect regions in a patient
      population with malignant airway stenosis. Treatment planning 4D CT images were
      obtained retrospectively for ten lung cancer patients with radiographically
      demonstrated airway obstruction due to gross tumor volume. Each patient also
      received a SPECT perfusion study within one week of the planning 4D CT, and prior
      to the initiation of treatment. Deformable image registration was used to map
      corresponding lung tissue elements between the extreme component phase images,
      from which quantitative three-dimensional (3D) images representing the local
      pulmonary specific ventilation were constructed. Semi-automated segmentation of
      the percentile perfusion distribution was performed to identify regional defects
      distal to the known obstructing lesion. Semi-automated segmentation was similarly
      performed by multiple observers to delineate corresponding defect regions
      depicted on 4D CT ventilation. Normalized Dice similarity coefficient (NDSC)
      indices were determined for each observer between SPECT perfusion and 4D CT
      ventilation defect regions to assess spatial overlap agreement. Tidal volumes
      determined from 4D CT ventilation were evaluated versus measurements obtained
      from lung parenchyma segmentation. Linear regression resulted in a linear fit
      with slope = 1.01 (R2 = 0.99). Respective values for the average DSC, NDSC(1 mm)
      and NDSC(2 mm) for all cases and multiple observers were 0.78, 0.88 and 0.99,
      indicating that, on average, spatial overlap agreement between ventilation and
      perfusion defect regions was comparable to the threshold for agreement within 1-2
      mm uncertainty. Corresponding coefficients of variation for all metrics were
      similarly in the range: 0.10%-19%. This study is the first to quantitatively
      assess 3D spatial overlap agreement between clinically acquired SPECT perfusion
      and specific ventilation from 4D CT. Results suggest high correlation between
      methods within the sub-population of lung cancer patients with malignant airway
      stenosis.

PMID- 22411125
TI  - "Culling the herd": eugenics and the conservation  movement in the United States,
      1900-1940.
AB  - While from a late twentieth- and early twenty-first century perspective, the
      ideologies of eugenics (controlled reproduction to eliminate the genetically
      unfit and promote the reproduction of the genetically fit) and environmental
      conservation and preservation, may seem incompatible, they were promoted
      simultaneously by a number of figures in the progressive era in the decades
      between 1900 and 1950. Common to the two movements were the desire to preserve
      the "best" in both the germ plasm of the human population and natural
      environments (including not only natural resources, but also undisturbed nature
      preserves such as state and national parks and forests). In both cases advocates
      sought to use the latest advances in science to bolster and promote their plans,
      which in good progressive style, involved governmental planning and social
      control. This article explores the interaction of eugenic and conservationist
      ideologies in the careers of Sacramento banker and developer Charles M. Goethe
      and his friend and mentor, wealthy New York lawyer Madison Grant. In particular,
      the article suggests how metaphors of nature supported active work in both
      arenas.

PMID- 22411126
TI  - Co-expression of endothelial and neuronal nitric oxide synthases in the
      developing vasculatures of the human fetal eye.
AB  - BACKGROUND: Nitric oxide (NO) is a multifunctional gaseous molecule that
      regulates various physiological functions in both neuronal and non-neuronal
      cells. NO is synthesized by nitric oxide synthases (NOSs), of which three
      isoforms have been identified. Neuronal NOS (nNOS) and endothelial NOS (eNOS)
      constitutively produce low levels of NO as a cell-signaling molecule in response
      to an increase in intracellular calcium concentration. Recent data have revealed
      a predominant role of eNOS in both angiogenesis and vasculogenesis. METHODS: The
      immunohistochemical localization of nNOS and eNOS was investigated during
      embryonic and fetal ocular vascular development from 7 to 21 weeks gestation (WG)
      on sections of cryopreserved tissue. RESULTS: eNOS was confined to endothelial
      cells of developing vessels at all ages studied. nNOS was prominent in nuclei of
      vascular endothelial and smooth muscle cells in the fetal vasculature of vitreous
      and choriocapillaris. nNOS was also prominent in the nuclei of CXCR4(+)
      progenitors in the inner retina and inner neuroblastic layer. CONCLUSIONS: These
      findings demonstrate co-expression of n- and eNOS isoforms in different
      compartments of vasoformative cells during development. Nuclear nNOS was present
      in vascular and nonvascular progenitors as well as endothelial cells and
      pericytes. This suggests that nNOS may play a role in the transcription
      regulatory systems in endothelial cells and pericytes during ocular hemo
      vasculogenesis, vasculogenesis, and angiogenesis.

PMID- 22411127
TI  - Clinical and pathological features of a non-crystalline form of Schnyder corneal
      dystrophy.

PMID- 22411128
TI  - Long-term outcome of primary versus secondary intraocular lens implantation after
      simultaneous removal of bilateral congenital cataract.
AB  - BACKGROUND: Long-term outcomes of intraocular lens (IOL) implantation for
      congenital cataract in children under 2 years old are still undetermined.
      METHODS: We retrospectively reviewed all cases of bilateral congenital cataract
      who had undergone simultaneous bilateral cataract removal with posterior
      capsulotomy and central anterior vitrectomy between 1990 and 2010. Patients
      randomly underwent primary IOL implantation or secondary IOL implantation after a
      period of contact lens wear. The two groups were compared for visual outcome and
      complications during follow-up. RESULTS: Cataract removal and primary IOL
      implantation was performed in 30 eyes (15 patients; nine males, six females) at a
      mean age of 6.8 +/- 4.2 months. After 79.31 +/- 63.4 months, best-corrected
      visual acuity (BCVA) was 0.53 +/- 0.36 EDTRS LogMAR. In 36 eyes (18 patients, 11
      males, seven females) the lens was removed at a mean age of 5.42 +/- 2.80 months,
      and after 32.0 +/- 6.1 months of contact lens utilization, secondary IOL
      implantation was performed. After 109.0 +/- 33.8 months, BCVA was 0.54 +/- 0.4
      ETDRS LogMAR. The association between age at surgery and final visual acuity and
      the difference between the two groups concerning type of cataract at baseline,
      BCVA and refractive error at last visit, incidence of posterior capsular
      opacification, glaucoma, strabismus, and nystagmus during follow-up were not
      significant (p > 0.05). Myopic shift was more frequent in eyes undergone primary
      IOL implantation (p < 0.001). CONCLUSIONS: Similar visual outcome and
      complications were observed during long-term follow-up after both primary and
      secondary IOL implantation following simultaneous bilateral congenital cataract
      removal with posterior capsulotomy and central anterior vitrectomy.

PMID- 22411129
TI  - Evaluation of the visual function in obstructive sleep apnea syndrome patients
      and normal-tension glaucoma by means of the multifocal visual evoked potentials.
AB  - BACKGROUND: This study was designed to objectively evaluate visual function and
      the causal relationship between sleep apnea and optic nerve dysfunction in
      patients with obstructive sleep apnea syndrome (OSAS) with or without diagnosis
      of normal-tension glaucoma (NTG) using multifocal visual evoked potentials
      (mfVEP). METHODS: This observational, cross-sectional study assessed 20 patients
      with recently diagnosed OSAS with or without NTG. Diagnosis of sleep apnea was
      based on overnight polysomnography (ApnoeScreen). All participants underwent a
      complete physical and ophthalmologic examination. MfVEP recordings obtained using
      VERIS software (Electro-Diagnostic Imaging, San Mateo, USA), SITA-standard 30-2
      automated perimetry (Humphrey Visual Field Analyzer II) and optic coherence
      tomography (Topcon 3D OCT-1000) exams were performed to evaluate the changes.
      RESULTS: Abnormal mfVEP amplitudes defects (interocular and monocular probability
      analysis) were found in 40% of the eyes in the non-glaucoma group and in 90% of
      eyes of the NTG patients. As well, delayed mfVEP latencies (interocular and
      monocular probability analysis) were seen in 30 and 60% of the eyes of the non
      glaucoma and NTG groups, respectively. The average RNFL (retinal nerve fiber
      layer) thickness was significantly reduced in the NTG eyes compared to the
      control database and the non-glaucoma eyes. On the Humphrey Visual Field total
      deviation analysis, all the NTG eyes showed significant clusters of abnormal
      points but none was detected in the non-glaucoma group eyes. However, the mfVEP
      amplitude and latency did not show any significant correlation with the standard
      perimetry and OCT variables, because the mfVEP technique was able to detect far
      more early visual defects in these patients. Systolic blood pressure, sleep
      efficiency, arousal index, mean and minimum arterial oxygen saturation (SaO(2)),
      time SaO(2) < 90%, oxyhemoglobin desaturation index, number of central and mixed
      apneas and apnea-hipopneas index were shown to be significantly correlated with
      mfVEP amplitude and latency. CONCLUSIONS: A significant incidence of subclinical
      optic nerve involvement, not detected with other structural and psychophysics
      diagnostic techniques was seen by means of the mfVEP. In this sense, the mfVEP
      may be a useful diagnostic tool in the clinic for early diagnosis and monitoring
      of optic nerve function abnormalities in patients with OSAS.

PMID- 22411130
TI  - Vitrectomy and internal limiting membrane peeling without gas tamponade for
      myopic foveoschisis.
AB  - PURPOSE: To evaluate the efficacy of vitrectomy including internal limiting
      membrane (ILM) peeling without gas tamponade for myopic foveoschisis (MF).
      METHOD: In this retrospective study, 15 eyes of 13 consecutive patients with MF
      underwent pars plana vitrectomy and ILM peeling without gas tamponade. The main
      outcomes were measured using best-corrected visual acuity (BCVA) and central
      macular thickness (CMT) on optical coherence tomography (OCT). RESULT: The mean
      refractive error was -11.0 +/- 8.2 diopters and mean axial length was 30.8 +/-
      2.6 mm. The mean BCVA increased from 0.78 +/- 0.53 to 0.61 +/- 0.75 logMAR unit
      (p = 0.05), and the mean CMT decreased from 405 +/- 143 MUm to 255 +/- 47 MUm (p
      = 0.002) during a follow-up of 11.8 months. OCT showed a complete resolution of
      the MF, with foveal reattachment in all eyes. Full-thickness macular hole
      developed in two eyes during follow-up. CONCLUSION: ILM peeling without gas
      tamponade results in favorable anatomical and visual outcomes.

PMID- 22411131
TI  - Intracranial hypertension as the presenting symptom of duodenal cancer.

PMID- 22411132
TI  - NMR-based insights into the conformational and interaction properties of Arkadia
      RING-H2 E3 Ub ligase.
AB  - Arkadia (Rnf111), an E3 Ubiquitin (Ub) ligase, amplifies TGF-beta signaling
      responses by targeting for degradation of the negative regulators Smad6/7 and the
      SnoN/Ski transcriptional repressors when they block the TGF-beta effectors
      Smad2/3. The E3 ligase activity of Arkadia depends on its C-terminal RING-H2
      domain that constitutes the docking site for the E2 Ub-conjugating enzyme
      carrying the activated Ub. We determined the nuclear magnetic resonance solution
      structure of Arkadia's RING-H2 domain and revealed a (beta)betabetaalpha fold,
      fully consistent with the expected "cross-brace" mode of Zn(II)-ligation. In
      addition, the interaction of the Arkadia RING-H2 domain with its E2 partner
      enzyme (UbcH5b) was examined through chemical shift perturbation. Proteins 2012.
      (c) 2012 Wiley Periodicals, Inc.

PMID- 22411133
TI  - Involvement of macroautophagy in multiple system atrophy and protein aggregate
      formation in oligodendrocytes.
AB  - alpha-Synuclein-containing glial cytoplasmic inclusions (GCIs) originating in
      oligodendrocytes are the characteristic hallmark for neuropathological diagnosis
      of multiple system atrophy (MSA). alpha-Synuclein can be degraded either by the
      proteasomal machinery or by autophagy, a lysosomal pathway which involves the
      formation of autophagosomes. The autophagosome takes up polyubiquitinated
      proteins via the autophagosomal protein LC3 and the ubiquitin binding protein
      p62. In the present study, neuropathological examination of seven MSA cases
      revealed that LC3-immunoreactivity is found to be associated with alpha-synuclein
      positive GCIs. These are also prominently stained by antibodies against p62 and
      ubiquitin, indicating that the autophagic pathway is upregulated during
      pathogenesis, which might be due to a persistent downregulation of proteasomal
      activity. To further address this question in a cellular context, we have
      investigated whether proteasomal inhibition in cultured rat brain
      oligodendrocytes promotes the recruitment of LC3 and p62 to protein aggregates.
      The data show that the autophagic marker LC3-II is upregulated and LC3 is
      recruited to the growing protein aggregates in cultured oligodendrocytes when the
      proteasome is impaired. However, aggregated proteins remain in the
      oligodendroglial cytoplasm and cannot be cleared efficiently. In conclusion,
      autophagy and the ubiquitin proteasome system are closely connected, and the
      presence of LC3-positive vesicles in GCIs indicates that macroautophagy
      participates in MSA pathogenesis.

PMID- 22411134
TI  - The voltage-dependent potassium channel subunit Kv2.1 regulates insulin secretion
      from rodent and human islets independently of its electrical function.
AB  - AIMS/HYPOTHESIS: It is thought that the voltage-dependent potassium channel
      subunit Kv2.1 (Kv2.1) regulates insulin secretion by controlling beta cell
      electrical excitability. However, this role of Kv2.1 in human insulin secretion
      has been questioned. Interestingly, Kv2.1 can also regulate exocytosis through
      direct interaction of its C-terminus with the soluble NSF attachment receptor
      (SNARE) protein, syntaxin 1A. We hypothesised that this interaction mediates
      insulin secretion independently of Kv2.1 electrical function. METHODS: Wild-type
      Kv2.1 or mutants lacking electrical function and syntaxin 1A binding were studied
      in rodent and human beta cells, and in INS-1 cells. Small intracellular fragments
      of the channel were used to disrupt native Kv2.1-syntaxin 1A complexes. Single
      cell exocytosis and ion channel currents were monitored by patch-clamp
      electrophysiology. Interaction between Kv2.1, syntaxin 1A and other SNARE
      proteins was probed by immunoprecipitation. Whole-islet Ca(2+)-responses were
      monitored by ratiometric Fura red fluorescence and insulin secretion was
      measured. RESULTS: Upregulation of Kv2.1 directly augmented beta cell exocytosis.
      This happened independently of channel electrical function, but was dependent on
      the Kv2.1 C-terminal syntaxin 1A-binding domain. Intracellular fragments of the
      Kv2.1 C-terminus disrupted native Kv2.1-syntaxin 1A interaction and impaired
      glucose-stimulated insulin secretion. This was not due to altered ion channel
      activity or impaired Ca(2+)-responses to glucose, but to reduced SNARE complex
      formation and Ca(2+)-dependent exocytosis. CONCLUSIONS/INTERPRETATION: Direct
      interaction between syntaxin 1A and the Kv2.1 C-terminus is required for
      efficient insulin exocytosis and glucose-stimulated insulin secretion. This
      demonstrates that native Kv2.1-syntaxin 1A interaction plays a key role in human
      insulin secretion, which is separate from the channel's electrical function.

PMID- 22411135
TI  - Type 2 diabetes mellitus worsens arterial stiffness in hypertensive patients
      through endothelial dysfunction.
AB  - AIMS/HYPOTHESIS: Endothelium-derived factors are thought to be physiological
      modulators of large artery stiffness. The aim of the study was to investigate
      whether endothelial function could be a determinant of arterial stiffness in
      essential hypertensive patients, in relation with the concomitant presence of
      type 2 diabetes mellitus. METHODS: The study included 341 participants (84
      hypertensive patients with and 175 without type 2 diabetes mellitus, 82 matched
      controls). Brachial artery endothelium-dependent flow-mediated dilation (FMD) was
      determined by high-resolution ultrasound and computerised edge detection system.
      Applanation tonometry was used to measure carotid-femoral pulse wave velocity
      (PWV). RESULTS: Hypertensive patients with diabetes had higher PWV (10.1 +/- 2.3
      m/s vs 8.6 +/- 1.4 m/s, p < 0.001) and lower FMD (3.51 +/- 2.07 vs 5.16 +/-
      2.96%, p < 0.001) than non-diabetic hypertensive patients, who showed impaired
      vascular function when compared with healthy participants (7.9 +/- 1.6 m/s and
      6.68 +/- 3.67%). FMD was significantly and negatively correlated to PWV only in
      hypertensive diabetic patients (r = -0.456, p < 0.001), but not in hypertensive
      normoglycaemic patients (r = -0.088, p = 0.248) or in healthy participants (r =
      0.008, p = 0.946). Multivariate analysis demonstrated that, in the diabetic
      group, FMD remained an independent predictor of PWV after adjustment for
      confounders (r(2) = 0.083, p = 0.003). Subgroup analysis performed in non
      diabetic hypertensive patients revealed that neither obesity nor the metabolic
      syndrome affected the relationship between FMD and PWV.
      CONCLUSIONS/INTERPRETATION: Endothelial dysfunction is a determinant of aortic
      stiffness in hypertensive diabetic patients but not in hypertensive patients
      without diabetes. These results suggest that type 2 diabetes mellitus on top of
      hypertension might worsen arterial compliance by endothelium-related mechanisms.

PMID- 22411136
TI  - Polymorphism of HMGA1 is associated with increased risk of type 2 diabetes among
      Chinese individuals.
AB  - AIMS/HYPOTHESIS: Variants of the high-mobility group A1 (HMGA1) gene have been
      shown to be associated with insulin resistance and type 2 diabetes in individuals
      of European origin. We aimed to determine whether this locus confers significant
      susceptibility to type 2 diabetes in the Han Chinese population, and thus cross
      race susceptibility to type 2 diabetes. METHODS: Polymorphisms in HMGA1 were
      identified by direct sequencing of genomic DNA derived from 192 Chinese
      participants (96 patients with type 2 diabetes and 96 controls). We then
      genotyped the common variant IVS5-13insC (c.136-14_136-13insC) in two other
      independent cohorts, including a total of 2,533 cases and 2,643 ethnically
      matched controls. RESULTS: We confirmed the association of the HMGA1 variant IVS5
      13insC (c.136-14_136-13insC) with type 2 diabetes with an OR of 1.34 (95% CI
      1.15, 1.56, p = 0.0002 under a dominant model, and 95% CI 1.16, 1.55, p = 0.0002
      under an additive model) in the Han Chinese population, corresponding to a
      population attributable risk fraction of 5.0%. CONCLUSIONS/INTERPRETATION: HMGA1
      is an important susceptibility locus that confers a high cross-race risk of the
      development of type 2 diabetes.

PMID- 22411137
TI  - [Unconscious plagiarism and author's request for withdrawal of his paper under
      consideration].

PMID- 22411138
TI  - Is coronary angiography an adequate diagnostic test to evaluate a young febrile
      patient with ST elevation?

PMID- 22411139
TI  - [Cardiac arrest and acute anterior STEMI induced by vancomycin infusion].

PMID- 22411140
TI  - A 13-year-old boy with a short QT interval.

PMID- 22411141
TI  - Evaluating patients for CRT, what is relevant: identifying responders or
      estimating the amount of potential response?

PMID- 22411142
TI  - ST-elevation myocardial infarction after acute carbon monoxide poisoning.

PMID- 22411144
TI  - Mitral valve leaflet strain imaging with echocardiography opens new windows to
      mitral valve study.

PMID- 22411143
TI  - Diphtheria myocarditis in Turkey after years.

PMID- 22411145
TI  - Two-in-one: single coronary ostium and mitral valve prolapsus in a young female
      with Alport syndrome.

PMID- 22411146
TI  - Amiodarone-induced pleural fluid is not always accompanied by a risk factor.

PMID- 22411147
TI  - Acute severe occlusion of the left main coronary artery following transcatheter
      aortic valve implantation.

PMID- 22411148
TI  - Big flooding in Thailand, the problem on loss following up of patients with
      hypertension.

PMID- 22411149
TI  - A giant tumor thrombi filling right ventricle in a thrombocytopenic patient with
      renal cell carcinoma.

PMID- 22411150
TI  - Two-and three-dimensional echocardiographic views of a prominent Chiari network
      prolapsing into right ventricle.

PMID- 22411151
TI  - Lipomatous hypertrophy of the interatrial septum demonstrated by three
      dimensional transesophageal echocardiography.

PMID- 22411152
TI  - [Mitral valve prolapse with mass-like appearance].

PMID- 22411153
TI  - Differential clubbing in an adult patient with patent ductus arteriosus and small
      ventricular septal defect.

PMID- 22411155
TI  - [Caricatures are so meaningful; increases are in positive way and one analysis:
      we are at the top].

PMID- 22411156
TI  - Ursolic acid directly promotes protein accretion in myotubes but does not affect
      myoblast proliferation.
AB  - Ursolic acid (UA) has been recently proposed as a potential candidate for the
      treatment of muscle wasting conditions because of its protein sparring/anabolic
      effects. Despite this finding, it is unknown whether this response is the
      consequence of a direct effect on the muscle fibre or if it is mediated by neural
      or other systemic factors. In the present study, we sought to determine if UA has
      direct effects in skeletal muscle cells, whether it can increase myoblast
      proliferation and whether UA can become myotoxic at higher doses. Our results
      demonstrate that UA directly promoted protein accretion in cultured myotubes but
      did not modulate myoblast proliferation. At higher doses, UA compromised cell
      viability in both myoblasts and myotubes. We conclude that the anabolic
      properties of UA seen in vivo and in vitro are likely a direct effect on the
      muscle cell, but at higher doses, the benefits decline in favour of a myotoxic
      outcome.

PMID- 22411157
TI  - Enantioselective synthesis of fluorene derivatives by chiral N-triflyl
      phosphoramide catalyzed double Friedel-Crafts alkylation reaction.
AB  - A highly efficient tandem double Friedel-Crafts reaction between indoles and 2
      formylbiphenyl derivatives by chiral N-triflyl phosphoramide was realized. Under
      mild conditions, various 9-(3-indolyl) fluorene derivatives have been obtained in
      good yield and up to 94% ee. Comparing to their corresponding chiral phosphoric
      acids, chiral N-triflyl phosphoramides catalyzed reactions led to products with
      opposite absolute configuration.

PMID- 22411158
TI  - Remote physician-pharmacist team-based cholesterol management in diabetes
      mellitus improves achievement of LDL-C target levels compared with access to
      health IT resources only.

PMID- 22411159
TI  - A review of long-term effects of low sodium diet versus high sodium diet on blood
      pressure, renin, aldosterone, catecholamines, cholesterol and triglyceride.

PMID- 22411160
TI  - Cochrane review: Non-nutritive sucking, kangaroo care and swaddling/facilitated
      tucking are observed to reduce procedural pain in infants and young children.

PMID- 22411161
TI  - Vitamin E increases prostate cancer risk in middle-aged men relative to placebo:
      no significant association observed with selenium, either alone or in combination
      with vitamin E.

PMID- 22411162
TI  - Don't keep blaming nurse education .....

PMID- 22411163
TI  - Use of non-aspirin NSAIDs during pregnancy may increase the risk of spontaneous
      abortion.

PMID- 22411164
TI  - What is a p value and what does it mean?

PMID- 22411165
TI  - Negative effects of item repetition on source memory.
AB  - In the present study, we explored how item repetition affects source memory for
      new item-feature associations (picture-location or picture-color). We presented
      line drawings varying numbers of times in Phase 1. In Phase 2, each drawing was
      presented once with a critical new feature. In Phase 3, we tested memory for the
      new source feature of each item from Phase 2. Experiments 1 and 2 demonstrated
      and replicated the negative effects of item repetition on incidental source
      memory. Prior item repetition also had a negative effect on source memory when
      different source dimensions were used in Phases 1 and 2 (Experiment 3) and when
      participants were explicitly instructed to learn source information in Phase 2
      (Experiments 4 and 5). Importantly, when the order between Phases 1 and 2 was
      reversed, such that item repetition occurred after the encoding of critical item
      source combinations, item repetition no longer affected source memory (Experiment
      6). Overall, our findings did not support predictions based on item
      predifferentiation, within-dimension source interference, or general interference
      from multiple traces of an item. Rather, the findings were consistent with the
      idea that prior item repetition reduces attention to subsequent presentations of
      the item, decreasing the likelihood that critical item-source associations will
      be encoded.

PMID- 22411166
TI  - Dacryoendoscopic observation and incidence of canalicular obstruction/stenosis
      associated with S-1, an oral anticancer drug.
AB  - PURPOSE: To report dacryoendoscopic observations and the incidence of lacrimal
      obstruction/stenosis associated with S-1, an oral anticancer drug. DESIGN:
      Retrospective, nonrandomized clinical trial. METHODS: A total of 52 patients (41
      men, 11 women; age 42-93 years) who were prescribed the anticancer drug S-1 were
      studied. Patients who suffered eye complaints following S-1 treatment underwent
      ophthalmic examination, probing and lacrimal irrigation. Patients whose tear
      meniscus was high or had abnormal lacrimal irrigation were evaluated by
      dacryoendoscopy. RESULTS: Overall, 5 of 52 S-1-treated patients (9.6%)
      experienced lacrimal passage stenosis/obstruction. One patient had punctal
      stenosis, and four patients had canalicular obstruction/stenosis. The onset of
      epiphora ranged from 2 to 8 months (4.4 +/- 2.2 months, mean +/- SD) after the
      initiation of chemotherapy. CONCLUSIONS: Patients receiving S-1 treatment should
      be evaluated for potential lacrimal disorders, particularly canalicular
      obstruction/stenosis. Dacryoendoscopic observation is effective for the diagnosis
      of this side effect.

PMID- 22411167
TI  - Novel emissive bio-inspired non-proteinogenic coumarin-alanine amino acid:
      fluorescent probe for polyfunctional systems.
AB  - Two new bio-inspired non-proteinogenic compounds L1 and L2, containing coumarin
      and/or acridine chromophores and bearing as spacer an alanine amino acid were
      successfully synthesized and fully characterized by elemental analysis, (1)H and
      (13)C NMR, infrared spectroscopy (KBr discs), melting point, ESI-TOF
      (electrospray ionization-time of flight-mass), UV-vis absorption and emission
      spectroscopy, fluorescence quantum yields and lifetime measurements. A relative
      fluorescence quantum yield of 0.02 was determined for both compounds. In L2 the
      presence of an intramolecular energy transfer from the coumarin to the acridine
      unit was observed. L1 and L2 are quite sensitive to the basicity of the
      environment. At alkaline values both compounds show a strong quenching in the
      fluorescence emission, attributed to the photoinduced electron transfer (PET).
      However, both deprotonated forms recover the emission with the addition of
      Zn(2+), Cd(2+) and Al(3+) metal ions. As multifunctional emissive probes, the
      titration of L1 and L2 with lanthanides (III), Eu(3+) and Tb(3+) was also
      explored as new visible bio-probes in the absence and in the presence of
      liposomes. In a liposomal environment a lower energy transfer was observed.

PMID- 22411168
TI  - Hormonal evidence supports the theory of selection in utero.
AB  - OBJECTIVES: Antagonists in the debate over whether the maternal stress response
      during pregnancy damages or culls fetuses have invoked the theory of selection in
      utero to support opposing positions. We describe how these opposing arguments
      arise from the same theory and offer a novel test to discriminate between them.
      Our test, rooted in reports from population endocrinology that human chorionic
      gonadotropin (hCG) signals fetal fitness, contributes not only to the debate over
      the fetal origins of illness, but also to the more basic literature concerned
      with whether and how natural selection in utero affects contemporary human
      populations. METHODS: We linked maternal serum hCG measurements from prenatal
      screening tests with data from the California Department of Public Health birth
      registry for the years 2001-2007. We used time series analysis to test the
      association between the number of live-born male singletons and median hCG
      concentration among males in monthly gestational cohorts. RESULTS: Among the 1.56
      million gestations in our analysis, we find that median hCG levels among male
      survivors of monthly conception cohorts rise as the number of male survivors
      falls. RESULTS: Elevated median hCG among relatively small male birth cohorts
      supports the theory of selection in utero and suggests that the maternal stress
      response culls cohorts in gestation by raising the fitness criterion for survival
      to birth.

PMID- 22411169
TI  - Airway epithelial cell differentiation during lung organogenesis requires
      C/EBPalpha and C/EBPbeta.
AB  - BACKGROUND: CCAAT/enhancer-binding protein (C/EBP)alpha is crucial for lung
      development and differentiation of the pulmonary epithelium. Conversely, no lung
      defects have been observed in C/EBPbeta-deficient mice, although C/EBPbeta trans
      activate pulmonary genes by binding to virtually identical DNA-sequences as
      C/EBPalpha. Thus, the pulmonary phenotype of mice lacking C/EBPbeta could be
      explained by functional replacement with C/EBPalpha. We investigated whether
      C/EBPalpha and C/EBPbeta have overlapping functions in regulating lung epithelial
      differentiation during organogenesis. Epithelial differentiation was assessed in
      mice with a lung epithelial-specific (SFTPC-Cre-mediated) deletion of C/EBPalpha
      (Cebpa(DeltaLE) ), C/EBPbeta (Cebpb(DeltaLE) ), or both genes (Cebpa(DeltaLE) ;
      Cebpb(DeltaLE) ). RESULTS: Both Cebpa(DeltaLE) mice and Cebpa(DeltaLE) ;
      Cebpb(DeltaLE) mice demonstrated severe pulmonary immaturity compared to wild
      type littermates, while no differences in lung histology or epithelial
      differentiation were observed in Cebpb(DeltaLE) mice. In contrast to
      Cebpa(DeltaLE) mice, Cebpa(DeltaLE) ; Cebpb(DeltaLE) mice also displayed
      undifferentiated Clara cells with markedly impaired protein and mRNA expression
      of Clara cell secretory protein (SCGB1A1), compared to wild-type littermates. In
      addition, ectopic mucus-producing cells were observed in the conducting airways
      of Cebpa(DeltaLE) ; Cebpb(DeltaLE) mice. CONCLUSIONS: Our findings demonstrate
      that C/EBPalpha and C/EBPbeta play pivotal, and partly overlapping roles in
      determining airway epithelial differentiation, with possible implications for
      tissue regeneration in lung homeostasis and disease.

PMID- 22411170
TI  - No risk of genetic disease in childhood cancer survivors' offspring found.

PMID- 22411171
TI  - Effects of continuous positive airway pressure on glycemic control and insulin
      resistance in patients with obstructive sleep apnea: a meta-analysis.
AB  - BACKGROUND: Previous studies addressing the question of whether continuous
      positive airway pressure (CPAP) could improve the insulin resistance and glucose
      control in patients with obstructive sleep apnea (OSA) have led to conflicting
      results. Therefore, we conducted the meta-analysis to evaluate the effects of
      CPAP on glycemic control and insulin resistance in OSA patients. METHODS: We
      searched PubMed, HighWire Press, Ovid Medline (R), Cochrane library, and EMBASE
      before December 2011 on original English language studies. The meta-analysis was
      conducted using Review Manager Version 5. RESULTS: The summary estimate for mean
      difference of homeostasis model assessment insulin resistance (HOMA) from 12 non
      diabetic studies was -0.55 (95 % CI, -0.91 to -0.20; P = 0.002). When compared
      with fasting blood glucose at baseline, 3 to 24 weeks of CPAP treatment did not
      improve glycemic control in non-diabetic subjects (-0.12; 95 % CI, -0.3 to 0.06;
      P = 0.20), as well as in diabetic subjects (-0.71; 95 % CI, -2.24 to 0.83; P =
      0.37). There were no intervention-related changes in body mass index.
      CONCLUSIONS: Our analysis showed that CPAP significantly improved insulin
      resistance in non-diabetic patients with moderate to severe OSA, while no
      significant change in body mass index was detected. Compared with fasting blood
      glucose at baseline, there was no change in glycemic control with CPAP. Further
      large-scale, randomized, and controlled studies are needed to evaluate the longer
      treatment and its possible effects on weight loss and glycemic homeostasis.

PMID- 22411172
TI  - Short-term severe thyroid hormone deficiency does not influence sleep parameters.
AB  - PURPOSE: The influence of short-term severe thyroid hormone deficiency on sleep
      is currently still unknown. Several studies have demonstrated an effect of long
      term hypothyroidism on sleep disorders due to anatomical changes of the pharynx
      or body mass. The aim of this preliminary study, however, is to evaluate the
      changes in sleep patterns of patients with short-term hypothyroidism to elucidate
      the isolated effect of thyroid hormone withdrawal before anatomical changes can
      potentially occur. METHODS: Ten patients with differentiated thyroid carcinoma
      were enrolled in this study. Two patients discontinued the study and one patient
      was finally excluded due to obesity, so that the datasets of seven patients were
      available for study analysis. During the course of carcinoma treatment, each
      patient had previously undergone total thyroidectomy and I-131 remnant ablation.
      Polysomnographic measurements were performed twice: (1) over the course of two
      consecutive nights during severe thyroid hormone deficiency after levothyroxine
      withdrawal and prior to further diagnostics and therapy and (2) during
      euthyroidism after substitution with levothyroxine. RESULTS: Comparison of the
      Epworth Sleepiness Scale during hypo- and euthyroidism for each patient revealed
      no statistically significant difference. Furthermore, the comparison of
      polysomnographic parameters like (1) apnea-hypopnea index, (2) the duration of
      various sleep stages, (3) duration of rapid eye movement sleep, (4) latency until
      rapid eye movement sleep, (5) total sleep time, (6) periodic leg movements, and
      (7) arousal index showed no statistically significant differences between the
      hypothyroid or euthyroid state. CONCLUSIONS: We conclude that, in this
      preliminary experimental setting, short-term severe thyroid hormone deficiency
      per se does not cause sleep disturbances and a feeling of fatigue as described in
      other studies may be due to changes in perception or brain metabolism during
      hypothyroidism.

PMID- 22411173
TI  - Increased sleep latency and reduced sleep duration in children with asthma.
AB  - STUDY OBJECTIVE: Sleep disturbance is reported to be more prevalent in children
      and adolescents with asthma than those without. However, this has not been
      described adequately using objective measures. The aim of this study was to
      objectively characterise sleep disturbance in asthmatic and non-asthmatic
      children and adolescents. METHODS: A retrospective analysis of polysomnography
      recordings from children aged 5-17 years old, with (n = 113) and without asthma
      (n = 104), referred for a sleep study over the period 2005-2010 at the Paediatric
      Sleep Unit, John Hunter Children's Hospital in Newcastle, NSW Australia, was
      carried out. RESULTS: Polysomnographic recordings were analysed to compare sleep
      quality and quantity between asthmatic and non-asthmatic children. Sleep latency
      was significantly longer in asthmatic children compared to controls. However,
      this result was significant for females only (46.2 (5.6) vs 33.2 (2.7) min, p <
      0.05). Male asthmatics had significantly shorter sleep duration (425.9 (5.4) vs
      441.8 (5.4) min, p < 0.05) than male controls. CONCLUSIONS: Sleep disturbance
      exists in children with asthma and manifests differently in males and females.
      Further investigation into the clinical implication of increased sleep latency
      and reduced sleep duration upon daytime functioning and lifestyle behaviours in
      children and adolescents with asthma is warranted.

PMID- 22411174
TI  - Protective effects of combined therapy of gliclazide with curcumin in
      experimental diabetic neuropathy in rats.
AB  - Diabetic neuropathy is the most common chronic complication of diabetes. The aim
      of the present study was to evaluate the protective effects of curcumin against
      neuropathy in gliclazide-treated diabetic rats. Diabetes was induced by an
      intraperitoneal injection of streptozotocin (45 mg/kg). Diabetic animals were
      given gliclazide (10 mg/kg, orally) alone or combined with curcumin (100 mg/kg,
      orally) or gabapentin (30 mg/kg, intraperitoneally as a positive control).
      Behavioral responses to thermal (hot plate and tail flick) and mechanical (tail
      pinch) pain, and some biochemical tests (serum glucose, C-peptide, peroxynitrite,
      lipid peroxides, and tumor necrosis factor-alpha) were assessed after 5
      consecutive weeks of daily treatment. Combined treatment of curcumin with
      gliclazide significantly increased hot-plate and tail-flick latencies in
      comparison with that of the diabetic control group. The threshold of mechanical
      hyperalgesia was also significantly elevated. Serum glucose and C-peptide levels
      were significantly increased in the combined treatment compared with the diabetic
      control group, whereas serum levels of peroxynitrite, lipid peroxide, and tumor
      necrosis factor-alpha production were significantly decreased. The data suggest
      that the combination of curcumin with gliclazide may protect against the
      development of diabetic neuropathy, with favorable effects with respect to the
      gliclazide/gabapentin combination.

PMID- 22411175
TI  - Study on evaporation characteristics of a sessile drop of sulfur mustard on
      glass.
AB  - The evaporation characteristics (evaporation rates and process) of a sessile drop
      of sulfur mustard on glass has been studied using a laboratory-sized wind tunnel,
      gas chromatograph mass spectrometry, and drop shape analysis. It showed that the
      evaporation rates of the droplet increased with temperature and air flow. The
      effect of temperature on the rates was more pronounced at lower air flow. Air
      flow was less effective at lower temperature. The contact angle of the droplet
      was initially observed as theta = 19.5 degrees  +/- 0.7 and decreased linearly
      with time until it switched to a constant mode.

PMID- 22411176
TI  - Persistence and dissipation kinetics of deltamethrin on chili in different agro
      climatic zones of India.
AB  - Multi-location supervised field trials were conducted at four different agro
      climatic locations in India to evaluate the dissipation pattern of deltamethrin
      on chili. Deltamethrin 10 EC was applied on chili @17.5 and 35 g a.i. ha(-1),
      samples of green chili were drawn at different time intervals and that of red
      chili and soil at harvest time and quantified by gas liquid chromatography
      equipped with electron capture detector. The identity of residues were confirmed
      by Gas Chromatograph-Mass Spectrophotometer in selective ion monitoring mode in
      mass range 181, 253 m/z. Limit of quantification of the method was found to be
      0.01 mg kg(-1). Half-life of deltamethrin at application rate of 17.5 g a.i. ha(
      1) varied from 0.36 to 1.99 days and at double the application rate was found to
      range from 0.38 to 2.06 days. Residues of deltamethrin were found below its
      determination limit of 0.01 mg kg(-1) in red chili and soil. On the basis of the
      data generated, Deltamethrin 10 EC has been registered for use on chili in India
      and its Maximum Residue Limit has been fixed as 0.05 MUg/g.

PMID- 22411178
TI  - Decision speed induces context effects in choice.
AB  - The context in which a decision occurs can influence the decision-making process
      in many ways. In the laboratory, this is often evident in the effects of recent
      decisions. For instance, many experiments combine easy and difficult decisions,
      such as when word frequency is manipulated in lexical decision. The "blocking
      effect" describes how such decisions differ depending on whether the conditions
      are presented in pure blocks (comprised purely of easy or hard stimuli) or mixed
      blocks (also known as a "mixing cost"). We present a novel extension to these
      context effects, demonstrating in two experiments that they can be induced using
      conditions with identical difficulty, but different timing properties. This
      suggests that explanations of context effects based on task difficulty or error
      monitoring alone might be insufficient, and suggest a role for decision time. In
      prior work, we suggested such a hypothesis under the assumption that observers
      minimize their decision time, subject to an accuracy constraint. Consistent with
      this explanation, we find that decisions in slower conditions were based on less
      evidence when they were experienced in mixed compared to pure blocks.

PMID- 22411177
TI  - Synthesis of porous zinc gallate prisms composed of highly oriented nanoparticles
      by an in situ conversion reaction.
AB  - Porous ZnGa(2)O(4) prisms assembled by highly oriented nanoparticles have been
      fabricated by an in situ chemical conversion approach. We report, for the first
      time, that a solid alpha-Ga(2)O(3) precursor can be directly converted into
      ZnGa(2)O(4) rather than through the intermediate GaOOH. Based on a detailed study
      of the evolution of ZnGa(2)O(4) prisms, a growth mechanism is proposed for the in
      situ conversion reaction. During this conversion process, the precursor
      morphology can be highly retained, which is attributed to the similar atomic
      arrangements of the Ga and O atoms and excellent matching of the lattice spacing
      between the alpha-Ga(2)O(3) and ZnGa(2)O(4) prisms. The direct reaction between
      the precursor alpha-Ga(2)O(3) and Zn(2+) ions is more efficient than that between
      the byproduct GaOOH and Zn(2+) ions. Moreover, the photoluminescent color of the
      ZnGa(2)O(4) phosphor can be tuned by doping with Mn(2+) ions. Efficient energy
      transfer (ET) from the host lattice to the Mn(2+) centers is observed, whereas ET
      from the defects to the Mn(2+) ions is prohibited. The fabricated ZnGa(2)O(4)
      products have potential in the field of display applications.

PMID- 22411179
TI  - Enhancing the comparability between part-list cueing and collaborative recall: a
      gradual part-list cueing paradigm.
AB  - The effects of part-list cueing and of collaborative recall in memory performance
      have been recently addressed as parallel phenomena. Notably they both impair
      recall (and boost frequency estimates) and they have been explained by the same
      underlying mechanisms. However, the comparability between the two paradigms is
      hindered by a number of procedural differences. The main contribution of this
      paper is the introduction of a new paradigm that makes standard part-list cueing
      and collaborative recall more comparable. In our study we compared free recall
      and frequency estimates of participants in a non-cueing condition with the same
      performance in a standard part-list cueing condition and in a condition in which
      part-list cues were gradually presented during recall (as it occurs in
      collaborative recall). Results indicate that the effects of part-list cueing
      continued to be reliable in both cueing conditions. Namely, recall was impaired
      and frequency estimates were boosted relatively to a non-cueing condition. The
      results obtained with this new method that enhances the direct comparability of
      the two paradigms provide further evidence for the parallel between the two
      effects.

PMID- 22411180
TI  - Similarity-based interference in a working memory numerical updating task: age
      related differences between younger and older adults.
AB  - Similarity among representations held simultaneously in working memory (WM) is a
      factor which increases interference and hinders performance. The aim of the
      current study was to investigate age-related differences between younger and
      older adults in a working memory numerical updating task, in which the similarity
      between information held in WM was manipulated. Results showed a higher
      susceptibility of older adults to similarity-based interference when accuracy,
      and not response times, was considered. It was concluded that older adults' WM
      difficulties appear to be due to the availability of stored information, which,
      in turn, might be related to the ability to generate distinctive representations
      and to the process of binding such representations to their context when similar
      information has to be processed in WM.

PMID- 22411181
TI  - Contingency learning with evaluative stimuli: testing the generality of
      contingency learning in a performance paradigm.
AB  - In two experiments, we tested the generality of the learning effects in the
      recently-introduced color-word contingency learning paradigm. Participants made
      speeded evaluative judgments to valenced target words. Each of a set of
      distracting nonwords was presented most often with either positive or negative
      target words. We observed that participants responded faster on trials that
      respected these contingencies than on trials that contradicted the contingencies.
      The contingencies also produced changes in liking: in a subsequent explicit
      evaluative rating task, participants rated positively-conditioned nonwords more
      positively than negatively-conditioned nonwords. Interestingly, contingency
      effects in the performance task correlated with this explicit rating effect in
      both experiments. In Experiment 2, all effects reported were independent of
      subjective and objective contingency awareness (which was completely lacking),
      even when awareness was measured at the item level. Our results reveal that
      learning in this type of performance task extends to nonword-valence
      contingencies and to responses different from those emitted during the
      performance task. We discuss the implications of these findings for theories
      about the processes that underlie contingency learning in performance tasks and
      for research on evaluative conditioning.

PMID- 22411182
TI  - A comparison of transfer-appropriate processing and multi-process frameworks for
      prospective memory performance.
AB  - We examined multi-process (MP) and transfer-appropriate processing descriptions
      of prospective memory (PM). Three conditions were compared that varied the
      overlap in processing type (perceptual/conceptual) between the ongoing and PM
      tasks such that two conditions involved a match of perceptual processing and one
      condition involved a mismatch in processing (conceptual ongoing task/perceptual
      PM task). One of the matched processing conditions also created a focal PM task,
      whereas the other two conditions were considered non-focal (Einstein & McDaniel,
      2005). PM task accuracy and ongoing task completion speed in baseline and PM task
      conditions were measured. Accuracy results indicated a higher PM task completion
      rate for the focal condition than the non-focal conditions, a finding that is
      consistent with predictions made by the MP view. However, reaction time (RT)
      analyses indicated that PM task cost did not differ across conditions when
      practice effects are considered. Thus, the PM accuracy results are consistent
      with a MP description of PM, but RT results did not support the MP view
      predictions regarding PM cost.

PMID- 22411184
TI  - Evolutionary perspectives on human aggression: introduction to the special issue.
AB  - The papers in this volume present varying approaches to human aggression, each
      from an evolutionary perspective. The evolutionary studies of aggression
      collected here all pursue aspects of patterns of response to environmental
      circumstances and consider explicitly how those circumstances shape the costs and
      benefits of behaving aggressively. All the authors understand various aspects of
      aggression as evolved adaptations but none believe that this implies we are
      doomed to continued violence, but rather that variation in aggression has
      evolutionary roots. These papers reveal several similarities between human and
      nonhuman aggression, including our response to physical strength as an indicator
      of fighting ability, testosterone response to competition, a sensitivity to
      paternity, and baseline features of intergroup aggression in foragers and chimps.
      There is also one paper tackling the phylogeny of these traits. The many
      differences between human and nonhuman aggression are also pursued here. Topics
      here include the impact of modern weapons and extremes of wealth and power on
      both the costs and benefits of fighting, and the scale to which coercion can
      promote aggression that acts against a fighter's own interests. Also the
      implications of large-scale human sociality are discussed.

PMID- 22411183
TI  - A simple and sensitive method for the demonstration of norepinephrine-storing
      adrenomedullary chromaffin cells.
AB  - The medulla of the adrenal gland is a neuroendocrine tissue in which
      catecholamine-storing chromaffin cells exist. The chromaffin cells are derived
      from neural crest cells and distinctly differentiated into two types of cells,
      epinephrine (E) (adrenaline)-storing and norepinephrine (NE) (noradrenaline)
      storing cells. Using histochemical or immunostaining methods, the two types of
      chromaffin cells have been differentially distinguished. However, difficulties
      and/or drawbacks of the procedures have somewhat restricted the progress of
      research in differential functions of E-storing and NE-storing cells. Here, we
      show a new method for the differential demonstration of these two cell types. We
      found that mouse and rat adrenomedullary cells are heterogeneously stained with
      Harris hematoxylin after treatment with citrate buffer at pH 6. The cell clusters
      stained with hematoxylin were positive for tyrosine hydroxylase, which is an
      enzyme involved in catecholamine biosynthesis. Furthermore, the cell clusters
      were negative for phenylethanolamine-N-methyl transferase, which is an enzyme
      responsible for the conversion from NE to E and expresses in E-storing chromaffin
      cells. Moreover, we found that the cell clusters stained with hematoxylin can
      also be stained with nitroblue tetrazolium at pH 11, using Hopsu and Makinen's
      method by which NE-storing chromaffin cells are stained. These observations
      indicate that the cytoplasm of NE-storing chromaffin cells is specifically
      stained with hematoxylin after treatment with citrate buffer at pH 6. This method
      will allow us to facilitate cell-type specific research of chromaffin cells.
      Indeed, this method revealed that alpha-synuclein selectively expresses in E
      storing chromaffin cells, but not in NE-storing chromaffin cells.

PMID- 22411185
TI  - Atypical polyarthritis as a major manifestation of light chain disease.

PMID- 22411186
TI  - Differential gene expression profiling of primary cutaneous melanoma and sentinel
      lymph node metastases.
AB  - Limited understanding of molecular mechanisms of metastasis in melanoma
      contributes to the absence of effective treatments. Increased knowledge of
      alterations in genes that underpin critical molecular events that lead to
      metastasis is essential. We have investigated the gene expression profiles of
      primary melanomas and melanoma metastases in sentinel lymph nodes. A total of 19
      samples (10 primary melanomas and 9 sentinel lymph node metastases) were
      evaluated. Melanoma cells were dissected from tissue blocks. Total mRNA was
      isolated, amplified, and labeled using an Ambion Recover All Total Nucleic Acid
      Isolation kit, Nu-GEN WT-Ovation formalin-fixed, paraffin-embedded RNA
      Amplification System, and FL-Ovation cDNA Biotin Module V2, respectively. Samples
      were hybridized to the Affymetrix Gene Chip Human U133 Plus 2.0 Array. Data were
      analyzed using Partek Genomics Suite Version 6.4. Genes selected showed >=2-fold
      difference in expression and P<5.00E-2. Validation studies used standard
      immunohistochemical assays. Hierarchical clustering disclosed two distinct
      groups: 10 primary melanomas and 9 sentinel lymph node metastases. Gene
      expression analysis identified 576 genes that showed significant differential
      expression. Most differences reflected decreased gene expression in metastases
      relative to primaries. Reduced gene expression in primaries was less frequent and
      less dramatic. Genes significantly increased or decreased in sentinel lymph node
      metastases were active in cell adhesion/structural integrity, tumor suppression,
      cell cycle regulation, and apoptosis. Validation studies indicate that MAGEC1
      (melanoma antigen family C1) and FCRL1 (Fc receptor-like 1) are involved in
      melanoma progression. There are striking differential gene expression patterns
      between primary and nodally metastatic melanomas. Similar findings were seen with
      autologous paired primary melanomas and sentinel lymph node metastases,
      supporting involvement of these gene alterations in evolution of metastases. With
      further study, it may be possible to determine the exact sequence of molecular
      events that underlie melanoma metastases.

PMID- 22411187
TI  - Combined coinage metal catalysis in natural product synthesis: total synthesis of
      (+)-varitriol and seven analogs.
AB  - A modular total synthesis of the natural product (+)-varitriol (1) and seven
      analogs was achieved by using combined coinage metal catalysis. Starting from
      enynol 13, reagent-controlled introduction of stereogenic centers and efficient
      center-to-axis-to-center chirality transfer viaalpha-hydroxyallene 5 afforded (+)
      varitriol with 6.4% yield over 10 steps.

PMID- 22411188
TI  - Investigating chelating sulfonamides and their use in metalloproteinase
      inhibitors.
AB  - Matrix metalloproteinase inhibitors (MMPi) utilize zinc-binding groups (ZBGs) to
      chelate the catalytic Zn(II) ion resulting in enzyme inhibition. Adapting
      findings from the literature of Zn(II) ion sensors, we previously reported
      chelating sulfonamide inhibitors of MMP-2, some of which showed excellent
      selectivity over other gelatinases (MMP-9). Herein, we greatly expand our
      investigation of chelating sulfonamides as MMP inhibitors (MMPi) with the
      synthesis and screening of several new libraries consisting of 2-phenyl-7
      sulfonamidobenzimidazole, 2-phenyl-7-sulfonamidobenzoxazole, 7
      sulfonamidobenzimidazole, 7-sulfonamidobenzoxazole, and 2-(2-sulfonamidophenyl)
      quinoline ZBG derivatives. A novel microwave irradiation synthetic procedure was
      utilized to rapidly and efficiently prepare these molecules. To better understand
      the coordination chemistry underlying these ZBGs, crystal structures of
      representative molecules with several first row transition metals were determined
      and differences in coordination preferences were considered. Surprisingly, only
      compounds with the 2-phenyl-7-sulfonamidobenzimidazole ZBG showed inhibition of
      MMP-2, suggesting that the specific structure of the ZBG can have a pronounced
      effect of inhibitory activity.

PMID- 22411189
TI  - Circumcision and the risk of prostate cancer.
AB  - BACKGROUND: Several lines of evidence support a role for infectious agents in the
      development of prostate cancer (PCa). In particular, sexually transmitted
      infections (STIs) have been implicated in PCa etiology, and studies have found
      that the risk of acquiring a STI can be reduced with circumcision. Therefore,
      circumcision may reduce PCa risk. METHODS: Participant data collected as part of
      2 population-based case-control studies of PCa were analyzed. Self-reported
      circumcision status, age at circumcision, and age at first sexual intercourse
      were recorded along with a history of STIs or prostatitis. Multivariate logistic
      regression was used to estimate the relative risk of PCa by circumcision status.
      RESULTS: Data from 1754 cases and 1645 controls were available. Circumcision
      before first sexual intercourse was associated with a 15% reduction in risk of
      PCa compared to that of uncircumcised men (95% confidence interval [CI], 0.73
      0.99). This risk reduction was observed for cases with both less aggressive (odds
      ratio, 0.88; 95% CI, 0.74-1.04) and more aggressive (odds ratio, 0.82; 95% CI,
      0.66-1.00) PCa features. CONCLUSIONS: Circumcision before first sexual
      intercourse is associated with a reduction in the relative risk of PCa in this
      study population. These findings are consistent with research supporting the
      infectious/inflammation pathway in prostate carcinogenesis.

PMID- 22411190
TI  - Interactions between relay helix and Src homology 1 (SH1) domain helix drive the
      converter domain rotation during the recovery stroke of myosin II.
AB  - Myosin motor protein exists in two alternative conformations, prerecovery state
      M* and postrecovery state M**, on adenosine triphosphate binding. The details of
      the M*-to-M** transition, known as the recovery stroke to reflect its role as the
      functional opposite of the force-generating power stroke, remain elusive. The
      defining feature of the postrecovery state is a kink in the relay helix, a key
      part of the protein involved in force generation. In this article, we determine
      the interactions that are responsible for the appearance of the kink. We design a
      series of computational models that contain three other segments, relay loop,
      converter domain, and Src homology 1 (SH1) domain helix, with which relay helix
      interacts and determine their structure in accurate replica exchange molecular
      dynamics simulations in explicit solvent. By conducting an exhaustive
      combinatorial search among different models, we find that: (1) the converter
      domain must be attached to the relay helix during the transition, so it does not
      interfere with other parts of the protein and (2) the structure of the relay
      helix is controlled by SH1 helix. The kink is strongly coupled to the position of
      SH1 helix. It arises as a result of direct interactions between SH1 and the relay
      helix and leads to a rotation of the C-terminal part of the relay helix, which is
      subsequently transmitted to the converter domain.

PMID- 22411192
TI  - Catheter ablation of ventricular tachycardia in ischaemic and non-ischaemic
      cardiomyopathy: where are we today? A clinical review.
AB  - According to the current guidelines, patients with ischaemic cardiomyopathy (ICM)
      or non-ischaemic cardiomyopathy (NICM) at risk for sudden cardiac death should
      undergo implantation of an implantable cardioverter-defibrillator (ICD). Although
      ICDs effectively terminate ventricular arrhythmias, the arrhythmogenic substrate
      remains unchanged or may progress over time, resulting in recurrent ICD shocks.
      Defibrillator shocks increase mortality and worsen quality of life. Evidence from
      two prospective randomized trials on outcome in patients with ischaemic heart
      disease undergoing catheter ablation for ventricular tachycardia (VT) suggests
      that ablation prevents recurrence of VT and decreases the number of ICD shocks.
      This review will highlight the recent progress made in the ablative treatment of
      VT in patients with ICM and NICM.

PMID- 22411195
TI  - Using anchoring vignettes to assess the comparability of self-rated feelings of
      sadness, lowness or depression in France and Vietnam.
AB  - General measures of self-rated health are collected routinely in national health
      surveys and widely used in the analyses of determinants of health and health care
      utilization. However, these subjective assessments can be influenced by health
      expectations (contextualized beliefs about health) that may vary systematically
      across individuals and be associated with their socio-demographic
      characteristics. Our objective is to contrast the impact of health expectations
      associated with respondent characteristics (reporting heterogeneity) on self
      rated feelings of sadness, lowness or depression obtained from general population
      samples in France and Vietnam. Based on self ratings and ratings in response to
      common anchoring vignettes depicting different levels of depression, we used
      nationally representative data from the World Health Survey conducted in France
      (2002) and Vietnam (2002-2003) and a modification of the standard probit model to
      test and adjust for reporting heterogeneity associated with individual
      characteristics. We find evidence of reporting heterogeneity within France and
      Vietnam and across the two countries. In particular we find that, when adjusted
      for reporting heterogeneity, sex is no longer significantly associated with self
      rated feelings of sadness, lowness or depression in France. Given the absence of
      clear biological markers in the definitions of depressive disorders and the
      substantial impact reporting heterogeneity is shown to have, measures of
      depressive disorders based on self-reports should be interpreted with caution.

PMID- 22411191
TI  - Depression, anxiety and personality dimensions in female first-degree relatives
      of alcohol-dependent probands.
AB  - A total of 136 with or without first-degree relatives with alcohol dependence
      were compared according to lifetime prevalence of psychiatric disorders and
      personality dimensions. Family history positive women showed significant higher
      prevalence rates of depression and agoraphobia, and exhibited lower scores on
      Reward Dependence, Self-Directedness and Cooperativeness dimensions.

PMID- 22411197
TI  - Adsorptive removal of Pb2+ form aqueous solution by macrocyclic
      calix[4]naphthalene: kinetic, thermodynamic, and isotherm analysis.
AB  - BACKGROUND: The adsorption characteristics of Pb(2+) ions from aqueous solutions
      onto calix[4]naphthalene have been investigated. METHOD: Calix[4]naphthalene was
      prepared by the condensation of 1-naphthol and formaldehyde (1:2) in presence of
      hydrochloric acid at 80  degrees C. The effect of various operation parameters,
      such as solution pH, initial metal ion concentration, contact time, and
      temperature, on the adsorption capacity of calix[4]naphthalene for Pb(2+) have
      been investigated. RESULT: Experimental results showed that the adsorption of
      Pb(2+) ions increased with the increase in solution pH and temperature. Langmuir
      and Freundlich isotherms models were used to describe the adsorption behavior of
      Pb(2+) by calix[4]naphthalene. Equilibrium data fitted well with the Langmuir
      isotherm model and the maximum adsorption capacity of calix[4]naphthalene for
      Pb(2+) at 30  degrees C was found to be 29.15 mg g(-1). Kinetic studies indicated
      that the adsorption followed pseudo-second order model and the thermodynamic
      studies revealed that the adsorption process was spontaneous and endothermic in
      nature. The obtained results demonstrated that calix[4]naphthalene can be used as
      an effective adsorbent for Pb(2+) ions removal from water.

PMID- 22411198
TI  - Effects of walnut husk washing waters and their phenolic constituents on
      horticultural species.
AB  - INTRODUCTION: The reuse of wastewaters for agricultural purposes is a common
      practice in many countries and is increasingly recommended by organizations that
      promote sustainable development. Yet, it is restricted by the potential negative
      impact of these materials on soil and crops. The aim of this study was therefore
      to evaluate the environmental impact of walnut husk washing waters (WHWW) and
      their organic fractions, in order to conceive their agricultural exploitation.
      DISCUSSION: Phytotoxicity tests and morphological investigations on
      representative plant species of horticultural interest indicated that WHWW and
      their organic fractions can elicit a concentration-dependent stimulating effect
      on the growth of radish, lettuce cv. cavolo Napoli with effects up to 165 %. An
      opposite inhibitory effect up to 70 % was observed on spinach and lettuce cv.
      Gentilina. Proapoptotic effects were observed by acridine orange/ethidium bromide
      assay in the species inhibited by WHWW treatment. High-performance liquid
      chromatography-mass spectrometry analysis of the WHWW revealed the presence of a
      main component which was extracted selectively in organic solvents and purified
      by preparative chromatography. Complete spectral analysis allowed identification
      as 4,8-dihydroxy-1-tetralone, commonly known as regiolone. Regiolone exhibited
      the same concentration-dependent activity on root elongation with a stimulation
      in the case of radish up to 135 % with respect to control. These results open
      perspectives in the exploitation of WHWW and the main phenolic constituent
      readily available by a straightforward isolation procedure as a natural
      fertilizer for specific crops.

PMID- 22411199
TI  - Exploratory data analysis in the study of 7Be present in atmospheric aerosols.
AB  - PURPOSE: Exploratory data analysis (EDA) is applied in this research to study the
      behavior of radioactive aerosols present in the surface atmosphere of Granada,
      using (7)Be as radiotracer. The reason for this study is to reduce the large
      number of parameters involved in understanding their behavior, given the
      complexity of the atmosphere. METHODS: Aerosol particles were collected weekly in
      Granada (Spain) over a 5-year period. Low-background gamma spectrometry was used
      to determine concentrations of (7)Be-aerosol activity. The variables studied
      were: (7)Be concentration, cosmic ray intensity, temperature, temperature
      interval, rainfall, relative humidity, and Saharan intrusions. Least significant
      difference test (LSD), hierarchical cluster analysis (HCA), and principal
      component analysis (PCA) with varimax rotation have been applied to study the
      datasets. RESULTS AND DISCUSSION: The results of our study reveal that aerosol
      behavior is represented by two principal components which explain 86.23 % of
      total variance. Components PC1 and PC2 respectively explain 74.61 and 11.62 % of
      total variance. PC1 explains the cyclical and seasonal pattern of the samples,
      while PC2 is related to the production of (7)Be. In addition, PCA and HCA show
      good distribution of the samples by families with two groups, summer and winter,
      at the extremes and spring-autumn in the middle. This result corroborates that
      there are no differences between spring and autumn in the climate of Granada.
      CONCLUSIONS: EDA has been found to be quite useful in studying the behavior of
      radioactive aerosols in the surface atmosphere of a city with the climate and
      geographical characteristics of Granada.

PMID- 22411200
TI  - Autism and pediatric practice: toward a medical home.
AB  - The pediatrician sees a child for 11 well child visits by their third birthday.
      The provision of continuous primary care supports development of trust with
      parents, provides opportunity for screening and surveillance of autism spectrum
      disorders (ASD), allows monitoring the progress of children requiring therapy,
      and a framework to support and educate families. Families of children with ASD
      are less likely to report that they receive care in a Medical Home, a practice
      providing coordinated, accessible, continuous, culturally competent care. They
      report less access to specialty and family focused care compared to other
      children with special health care needs. It is a major challenge to identify and
      effect the solutions necessary to bring Medical Home care to all children with
      ASD.

PMID- 22411201
TI  - Incomplete splicing, cell division defects, and hematopoietic blockage in dhx8
      mutant zebrafish.
AB  - BACKGROUND: Vertebrate hematopoiesis is a complex developmental process that is
      controlled by genes in diverse pathways. To identify novel genes involved in
      early hematopoiesis, we conducted an ENU (N-ethyl-N-nitrosourea) mutagenesis
      screen in zebrafish. The mummy (mmy) line was investigated because of its
      multiple hematopoietic defects. RESULTS: Homozygous mmy embryos lacked
      circulating blood cell types and were dead by 30 hr post-fertilization (hpf). The
      mmy mutants did not express myeloid markers and had significantly decreased
      expression of progenitor and erythroid markers in primitive hematopoiesis.
      Through positional cloning, we identified a truncation mutation in dhx8 in the
      mmy fish. dhx8 is the zebrafish ortholog of the yeast splicing factor prp22,
      which is a DEAH-box RNA helicase. mmy mutants had splicing defects in many genes,
      including several hematopoietic genes. mmy embryos also showed cell division
      defects as characterized by disorganized mitotic spindles and formation of
      multiple spindle poles in mitotic cells. These cell division defects were
      confirmed by DHX8 knockdown in HeLa cells. CONCLUSIONS: Together, our results
      confirm that dhx8 is involved in mRNA splicing and suggest that it is also
      important for cell division during mitosis. This is the first vertebrate model
      for dhx8, whose function is essential for primitive hematopoiesis in developing
      embryos.

PMID- 22411202
TI  - Sentinel lymph node biopsy for T1/T2 oral cavity squamous cell carcinoma--a
      prospective case series.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) is an established technique in
      breast and melanoma surgery and is gaining acceptance in the management of oral
      cavity squamous cell carcinoma. We report a single institution's experience of
      SLNB between 2006 and 2010. METHODS: Prospective consecutive cohort study of 59
      patients recruited between 2006 and 2010. All patients underwent SLNB with
      preoperative lymphoscintigraphy, intraoperative blue dye, and handheld gamma
      probe. Sentinel nodes were evaluated with step-serial sectioning and
      immunohistochemistry. Endpoints included: overall survival (OS), disease-specific
      survival (DSS), local recurrence-free survival (LRFS), and regional recurrence
      free survival (RRFS). RESULTS: A total of 59 patients (36 male and 23 female)
      were operated on. Of these, 42 patients (71%) were pT1 and 17 patients (29%) were
      pT2. In two patients the sentinel node was not identified and proceeded to
      elective neck dissection. A total of 150 nodes were harvested from the remaining
      57 patients of which 21 nodes were positive in 17 patients; three patients had
      positive contralateral nodes. The 2-year OS, DSS, LRFS, and RRFS for the SLNB
      negative patients were 97.5, 100, 95.8, and 95.8% and for the SLNB positive
      patients 68.2, 81.8, 83.9, and 100% respectively. Only OS and DSS approached
      statistical significance with P values of 0.07 and 0.06. CONCLUSIONS: SLNB is a
      safe and accurate diagnostic technique for staging the neck with a negative
      predictive value in our series of 97.5%. Furthermore, in our series three
      patients (5%) had positive contralateral neck drainage that would have been
      missed by conventional ipsilateral neck dissection.

PMID- 22411203
TI  - Managing patients at high risk for hereditary breast cancer: a guide for the
      practicing physician.

PMID- 22411204
TI  - Intratumoral IL-17+ cells and neutrophils show strong prognostic significance in
      intrahepatic cholangiocarcinoma.
AB  - BACKGROUND: Inflammatory reactions at a tumor site have both detrimental and
      beneficial effects on tumor progression. This study was designed to assess the
      clinical significance of tumor-infiltrating inflammatory cells in patients with
      intrahepatic cholangiocarcinoma (ICC). METHODS: A total of 123 consecutive ICC
      patients who underwent curative resection were enrolled. Tissue microarray and
      immunohistochemistry were used to analyze the distribution and clinical relevance
      of IL-17(+), FOXP3(+), CD8(+), CD66b(+) cells, and microvessel density (CD34) in
      different microanatomical areas. RESULTS: IL-17(+) cells, FOXP3(+) lymphocytes,
      CD66b(+) neutrophils, and microvessels were enriched predominantly in intratumor
      (IT) area, whereas CD8(+) lymphocytes were most abundant in tumor invasive front.
      On univariate analyses, increasing IL-17 (IT) (+) and neutrophils(IT) were
      significantly associated with worse patient survival. Multivariate analyses
      revealed that IL-17 (IT) (+) (hazard ratio [HR] = 1.59; 95% confidence interval
      [CI], 1.05-2.41; P = 0.028), neutrophils(IT) (HR = 1.76; 95% CI, 1.16-2.65; P =
      0.007), and their combination (HR 2.8; 95% CI 1.72-4.57; P < 0.001) were
      independent prognostic factors, which were superior to conventional
      clinicopathologic features, such as intrahepatic metastasis and TNM stage. IL-17
      (IT) (+) significantly correlated with the presence of lymph node metastasis,
      intrahepatic metastasis, and advanced stages, whereas neutrophils(IT) correlated
      with the presence of vascular invasion. In addition, significant positive
      correlations were detected among densities of IL-17(+) cells, neutrophils, and
      microvessel density. CONCLUSIONS: Our data suggested that intratumor IL-17(+)
      cells, neutrophils are novel, powerful predictors of prognosis in patients with
      ICC.

PMID- 22411205
TI  - Impact of obesity and body fat distribution on survival after
      pancreaticoduodenectomy for pancreatic adenocarcinoma.
AB  - BACKGROUND: Epidemiologic studies have reported a positive correlation between
      body mass index (BMI) and pancreatic cancer risk, but clinical relevance of
      obesity and/or body fat distribution on tumor characteristics and cancer-related
      outcome remain controversial. We sought to assess the influence of obesity and
      body fat distribution on pathologic characteristics and survival after
      pancreaticoduodenectomy for pancreatic adenocarcinoma. METHODS: Demographic and
      biometric data were collected on 328 patients undergoing pancreaticoduodenectomy
      for pancreatic ductal adenocarcinoma. In a subset of patients, pancreatic fatty
      infiltration and fibrosis were assessed pathologically, and visceral fat area
      (VFA) was evaluated. Influence of BMI and body fat distribution on tumor
      characteristics and survival were evaluated. RESULTS: A significant positive
      correlation between BMI and VFA was observed, with a wide range of VFA value
      within each BMI class. According to BMI or VFA distribution, there were no
      significant differences in patient characteristics, intraoperative or
      perioperative outcome, or pathologic characteristics, with the exception of
      significantly higher blood loss in patients with an increased body weight or VFA.
      Unadjusted overall and disease-free survival between BMI class and VFA quartile
      were not significantly different. CONCLUSIONS: In this study, obesity and body
      fat distribution were not correlated with specific tumor characteristics or
      cancer-related outcome.

PMID- 22411206
TI  - Fesoterodine in randomised clinical trials: an updated systematic clinical review
      of efficacy and safety.
AB  - INTRODUCTION AND HYPOTHESIS: This is a systematic review of clinical data
      assessing the safety, efficacy and tolerability of fesoterodine in randomised
      control trials (RCTs) in the treatment of overactive bladder (OAB). METHODS: We
      performed a MEDLINE literature search of articles published between 2005 and 2010
      regarding the efficacy and safety of fesoterodine. The US Food and Drug
      Administration Web site was also searched for RCTs. RESULTS: Two studies
      demonstrated significant improvement of OAB symptoms with fesoterodine compared
      with placebo. Two phase III studies showed both doses of fesoterodine to be more
      effective than placebo for most symptoms. Another phase III trial confirmed the
      superiority of 8 mg fesoterodine compared with tolterodine ER 4 mg. Dry mouth was
      the commonest side effect. CONCLUSIONS: Fesoterodine is effective for treating
      OAB symptoms. Its once-daily dosing regime and the flexibility to increase the
      dose are appealing factors.

PMID- 22411207
TI  - Stress urinary incontinence in climacteric women in a northeastern Brazilian
      municipality: a household survey.
AB  - INTRODUCTION AND HYPOTHESIS: Low socioeconomic factors may influence the
      development of stress urinary incontinence (SUI). Thus far, there is little
      research available on SUI in developing countries. We aimed to determine whether
      the prevalence of SUI in a northeastern Brazilian municipality was higher or
      lower than in the general female population. METHODS: Cross-sectional household
      cluster study of 1,180 climacteric women in the Sao Luis municipality (Maranhao
      state, Brazil) was conducted using a standardized questionnaire that was
      previously tested in a pilot study and administered by interviewers to obtain
      socioeconomic and cultural information, climacteric aspects, and life habits
      related to SUI. RESULTS: From this population, 15.34% (n = 181) had SUI; this
      prevalence did not change with age. More than half (57.92%) of the patients
      replied that they had not consulted a physician for their SUI. The presence of
      SUI was not associated with any socioeconomic or gynecological variables after
      multivariate analysis. CONCLUSIONS: The prevalence of SUI in Sao Luis was similar
      to the rates observed in the general global female population. Socioeconomic and
      gynecological variables were not associated with SUI.

PMID- 22411208
TI  - The efficacy of posterior tibial nerve stimulation for the treatment of
      overactive bladder in women: a systematic review.
AB  - INTRODUCTION AND HYPOTHESIS: Posterior tibial nerve stimulation (PTNS) is a
      percutaneous method of peripheral, sacral neuromodulation. Its current use is
      limited; however, published data suggest PTNS may be an effective treatment for
      overactive bladder (OAB). METHODS: We systematically reviewed the literature on
      PTNS for treatment of idiopathic OAB in women from January 2000 to August 2010
      published in English in MEDLINE/PubMed, Embase, and Cochrane databases. We
      included randomized controlled trials or observational studies reporting
      objective outcome measures with the use of either the Urgent PC or Stoller
      Afferent Nerve Stimulator (SANS) for PTNS. Studies were considered "good quality"
      if results from objective measures were provided for >=20 women, results
      distinguished between type of OAB symptom, and data were reported separately for
      female subjects. RESULTS: Of the 136 identified articles, 17 met inclusion
      criteria for data abstraction; 4 of the 17 studies met our criteria for good
      quality and reported success rates of 54-93 %. Recurrent limitations in the
      literature were pooling of results for male and female subjects and lack of
      differentiation in the data on specific symptoms of OAB treated. Short-term
      follow-up and infrequent use of a control arm were also noted shortcomings of
      reviewed studies. CONCLUSIONS: Limited high quality data exist on PTNS for OAB in
      women. Although initial studies have demonstrated promise, more comprehensive
      evaluation of PTNS is needed to support its universal use for the treatment of
      OAB in women.

PMID- 22411209
TI  - Genital prolapse in adult women with classical bladder exstrophy.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this paper is to study the incidence and
      risk factors for genital prolapse in adult women with bladder exstrophy and to
      describe the long-term outcome of the Gore-Tex wrap procedure for genital
      prolapse. METHODS: A retrospective observational study on adult women with
      classical bladder exstrophy in a tertiary referral centre for disorders of sex
      development, including complex urogenital anomalies. Medical notes were reviewed
      and a confidential postal questionnaire on urinary continence and symptoms of
      prolapse was carried out. RESULTS: Fifty-two women with bladder exstrophy and a
      mean age of 39 years (range 23 to 63) were identified, of whom 27 patients (52%)
      developed pelvic organ prolapse. Twenty-three out of 27 (85%) were treated
      surgically while only 4 patients were managed expectantly. Risk factors for
      prolapse included pregnancy in 10 (37%) patients and introitoplasty in 1 patient
      (4%). Of the 23 women treated surgically, 16 (70%) were treated using a Gore-Tex
      wrap, while 7 had other surgical procedures including colposuspension and
      hysterosacrocolpopexy. In the Gore-Tex wrap group, 12 out of 16 patients (75%)
      had had a successful result after the first repair compared with 2 out of the 7
      patients (28%) in the group treated using other procedures. Mean follow-up was 8
      years (range 1-15). One patient developed an infection after the procedure and
      another patient had Gore-Tex erosion. CONCLUSIONS: Prolapse is a common
      gynaecological complaint in adult women with bladder exstrophy and the majority
      will require treatment. At present the Gore-Tex wrap offers good results with a
      low rate of serious complications.

PMID- 22411210
TI  - What do we do when a midurethral tape fails? Rediscovery of open colposuspension
      as a salvage continence operation.
AB  - INTRODUCTION AND HYPOTHESIS: Our aim was to evaluate the outcome of open
      colposuspension for women with urodynamic stress incontinence who had previously
      undergone a failed midurethral tape. METHODS: A retrospective study of 13 women
      who had undergone open colposuspension after a failed midurethral tape was
      conducted. RESULTS: At a median follow-up of 12 months, subjective and objective
      cure rate were 85% and 77%, respectively. Thirty percent of the women developed
      de novo detrusor overactivity that responded to antimuscarinic treatment. Long
      term voiding difficulty was observed in only one patient, who performed clean
      intermittent self-catheterization for 3 months. Posterior vaginal wall prolapse
      requiring pelvic floor repair was found in three women (23%) postoperatively.
      CONCLUSIONS: Open colposuspension is an effective option for treating persistent
      or recurrent stress urinary incontinence after failed midurethral tape, with a
      high success rate.

PMID- 22411211
TI  - Use of mirabegron in treating overactive bladder.
AB  - The lack of an alternative to antimuscarinics has led to the search for new drug
      targets for overactive bladder (OAB) symptoms. The presence of beta-3
      adrenoreceptors in the bladder has been confirmed, and they are known to have a
      role in bladder relaxation. Targeting these receptors improves bladder compliance
      on filling and increases bladder capacity. MEDLINE literature search on efficacy
      and safety of mirabegron was performed. The US Food and Drug Administration Web
      site, clinicaltrials.gov, and controlled-trials.com online trial registries were
      searched for English-language articles containing the term "mirabegron". Finally,
      abstracts from recent International scientific meetings were searched for
      randomised controlled trials (RCTs). Studies show that mirabegron reduces the
      number of micturitions and incontinence episodes in a 24-h period compared with
      placebo. Dry mouth and gastrointestinal disturbances are the most common side
      effects, but these have been rated as mild to moderate. A small rise in mean
      heart rate and blood pressure has been shown. Further investigations are ongoing
      and results are awaited. Although mirabegron is metabolised by CYP2D6, it is also
      thought to inhibit the activity of this enzyme. Therefore, potential drug
      interactions with other CYP2D6 substrates need to be further studied. Mirabegron
      is a promising alternative to antimuscarinics. Further information on its long
      term use in terms of efficacy, safety, and tolerability is awaited.

PMID- 22411212
TI  - Avoidance of activities in early symptomatic knee osteoarthritis: results from
      the CHECK cohort.
AB  - BACKGROUND: Pain-related avoidance of activities is hypothesized to lead to lower
      muscle strength and thereby activity limitations. Negative affect (e.g., low
      vitality, depression) is thought to strengthen the tendency to avoid activities.
      PURPOSE: The aim of this study was to assess the validity of this "avoidance
      model" in patients with early symptomatic knee osteoarthritis (OA). METHODS:
      Cross-sectional data (n=151) were used. The associations between pain, negative
      affect, avoidance, muscle strength, and activity limitations were modeled using
      structural equation modeling. RESULTS: Pain and negative affect were associated
      with lower muscle strength via avoidance (mediation by avoidance). Avoidance was
      associated with activity limitations via lower muscle strength (mediation by
      muscle strength). There were also direct associations between pain, negative
      affect, avoidance, muscle strength, and activity limitations. CONCLUSIONS: The
      results support the validity of the avoidance model, which explains the
      associations between pain, negative affect, avoidance, muscle strength, and
      activity limitations in patients with early symptomatic knee OA.

PMID- 22411213
TI  - Evaluation of occupational exposure: comparison of biological and environmental
      variabilities using physiologically based toxicokinetic modeling.
AB  - PURPOSE: Few studies compare the variabilities that characterize environmental
      (EM) and biological monitoring (BM) data. Indeed, comparing their respective
      variabilities can help to identify the best strategy for evaluating occupational
      exposure. The objective of this study is to quantify the biological variability
      associated with 18 bio-indicators currently used in work environments. METHOD:
      Intra-individual (BV(intra)), inter-individual (BV(inter)), and total biological
      variability (BV(total)) were quantified using validated physiologically based
      toxicokinetic (PBTK) models coupled with Monte Carlo simulations. Two
      environmental exposure profiles with different levels of variability were
      considered (GSD of 1.5 and 2.0). RESULTS: PBTK models coupled with Monte Carlo
      simulations were successfully used to predict the biological variability of
      biological exposure indicators. The predicted values follow a lognormal
      distribution, characterized by GSD ranging from 1.1 to 2.3. Our results show that
      there is a link between biological variability and the half-life of bio
      indicators, since BV(intra) and BV(total) both decrease as the biological
      indicator half-lives increase. BV(intra) is always lower than the variability in
      the air concentrations. On an individual basis, this means that the variability
      associated with the measurement of biological indicators is always lower than the
      variability characterizing airborne levels of contaminants. For a group of
      workers, BM is less variable than EM for bio-indicators with half-lives longer
      than 10-15 h. CONCLUSION: The variability data obtained in the present study can
      be useful in the development of BM strategies for exposure assessment and can be
      used to calculate the number of samples required for guiding industrial
      hygienists or medical doctors in decision-making.

PMID- 22411214
TI  - Skin symptoms in bakery and auto body shop workers: associations with exposure
      and respiratory symptoms.
AB  - PURPOSE: Despite the importance of skin exposure, studies of skin symptoms in
      relation to exposure and respiratory symptoms are rare. The goals of this study
      were to describe exposure-response relationships for skin symptoms, and to
      investigate associations between skin and respiratory symptoms in bakery and auto
      body shop workers. METHODS: Data from previous studies of bakery and auto body
      shop workers were analyzed. Average exposure estimates for wheat allergen and
      isocyanates were used. Generalized linear models were constructed to describe the
      relationships between exposure and skin symptoms, as well as between skin and
      respiratory symptoms. RESULTS: Data from 723 bakery and 473 auto body shop
      workers were analyzed. In total, 5.3% of bakery and 6.1% of auto body shop
      workers were female; subjects' mean age was 39 and 38 years, respectively.
      Exposure-response relationships were observed in auto body shop workers for itchy
      or dry skin (PR 1.55, 95% CI 1.2-2.0) and work-related itchy skin (PR 1.97, 95%
      CI 1.2-3.3). A possible exposure-response relationship for work-related itchy
      skin in bakery workers did not reach statistical significance. In both groups,
      reporting skin symptoms was strongly and significantly associated with reporting
      respiratory symptoms, both work-related and non-work-related. CONCLUSIONS:
      Exposure-response relationships were observed for skin symptoms in auto body shop
      workers. The lack of significant exposure-response associations in bakery workers
      should be interpreted cautiously. Workers who reported skin symptoms were up to
      four times more likely to report respiratory symptoms. Improved awareness of both
      skin and respiratory outcomes in exposed workers is needed.

PMID- 22411215
TI  - Surface display of human serum albumin on Bacillus subtilis spores for oral
      administration.
AB  - Human serum albumin (HSA) is the major protein component of human plasma. To
      date, HSA for clinical uses is mostly produced by fractionation of human whole
      blood, which is accompanied by a lot of limitations. To obtain long-term
      bioactive albumin, we used hsa as a foreign gene and constructed a recombinant
      plasmid pJS700-HSA which carries a recombinant gene cotC-hsa under the control of
      cotC promoter. Plasmid pJS700-HSA was transformed into Bacillus subtilis by
      double cross-over and an amylase inactivated mutant was produced. After induction
      of spore formation, western blot and fluorescence immunoassay were used to
      monitor HSA surface expression on spores. We estimated that HSA displayed on the
      spore accounted for 0.135 % of the total spore proteins and about 0.023 fg HSA
      were exposed on the surface of each spore. Oral administration to mice with
      spores displaying HSA implied that the recombinant spores may have potential
      ability to increase the serum albumin level in vivo due to the resistant
      characters of spores.

PMID- 22411216
TI  - Small organometallic compounds as antibacterial agents.
AB  - The emergence of bacterial resistance to commercial antibiotics is an issue of
      global importance. During the last two decades, the number of antibacterial
      agents that have been discovered and introduced into the market has steadily
      declined and failed to meet the challenges posed by rapidly increasing resistance
      of the pathogens against common antibacterial drugs. The development of new
      classes of compounds to control the virulence of the pathogens is therefore
      urgently required. This perspective describes the historical development in brief
      and recent advances on the preparation of small organometallic compounds as new
      classes of antibacterial agents with potential for clinical development.

PMID- 22411217
TI  - [The role of homocysteine and methylenetetrahydrofolate reductase, methionine
      synthase, methionine synthase reductase polymorphisms in the development of
      cardiovascular diseases and hypertension].
AB  - Cardiovascular diseases (CVDs) are the leading causes of death in the developed
      countries. Elevated homocysteine level is as an independent risk factor of CVDs.
      The C677T and A1298C variants of methylenetetrahydrofolate reductase gene (MTHFR)
      have been shown to influence folate and homocysteine metabolisms. However, the
      relationship between MTHFR polymorphisms and hyperhomocysteinemia has not been
      well established yet. The gene variants were also reported to be associated with
      CVDs. In addition, the C677T polymorphisms may play a role in the development of
      hypertension. Recent research evidence has suggested that MTHFR variants might be
      independently linked to CVDs and hypertension, because of the involvement of the
      MTHFR enzyme product (5-methyl-tetrahydrofolate /5-MTHF) in the regulation of
      endothelial functions. Further research is required to investigate the
      association between gene polymorphisms of folate-metabolizing enzymes and CVDs,
      and to identify the possible role of the relevant gene variants in the molecular
      pathogenesis of hyperhomocysteinemia.

PMID- 22411218
TI  - [Successful completed pregnancies in patients with systemic lupus erythematosus].
AB  - Systemic lupus erythematosus is a chronic autoimmune disorder which affects women
      with child bearing potential. AIM: The aim of this study was to investigate the
      successful pregnancies in patients with lupus in the past 10 years. Women were
      followed up at the 3rd Department of Internal Medicine, University of Debrecen.
      RESULTS: During this investigated period, 26 patients became pregnant. Seven
      patients had a positive history for lupus before the pregnancy. A total of 29
      children were born. The mean gestational age was 35 weeks. The average birth
      weight was 2415 grams. Toxemic pregnancy was the most common complication found
      in 9 patients. Lupus nephritis activity occurred in 2 patients, and 1 of them had
      it for the first time during the course of her disease. CONCLUSIONS: In the past
      years, the number of pregnancies in patients with lupus has been increasing. Due
      to proper patient care and education, the outcome is more favourable.

PMID- 22411219
TI  - [Validation of the Hungarian version of Alzheimer's Disease Assessment Scale-
      cognitive subscale].
AB  - The cognitive subscale of the Alzheimer's Disease Assessment Scale is the most
      widely used test in the diagnostic and research work of Alzheimer's disease.
      AIMS: The aim of this study was to validate and investigate reliability of the
      Hungarian version of the Alzheimer's Disease Assessment Scale in patients with
      Alzheimer's disease and healthy control subjects. METHODS: sixty-six patients
      with mild and moderate Alzheimer's disease and 47 non-demented control subjects
      were recruited for the study. The cognitive status was established by the
      Hungarian version of the Alzheimer's Disease Assessment Scale and Mini Mental
      State Examination. Discriminative validity, the relation between age and
      education and Alzheimer's Disease Assessment Scale, and the sensitivity and
      specificity of the test were determined. RESULTS: Both the Mini Mental State
      Examination and the Alzheimer's Disease Assessment Scale had significant
      potential in differentiating between patients with mild and moderate stages of
      Alzheimer's disease and control subjects. A very strong negative correlation was
      established between the scores of the Mini Mental State Examination and the
      Alzheimer's Disease Assessment Scale in the Alzheimer's disease group. The
      Alzheimer's Disease Assessment Scale showed slightly negative relationship
      between education and cognitive performance, whereas a positive correlation
      between age and Alzheimer's Disease Assessment Scale scores was detected only in
      the control group. According to the analysis of the ROC curve, the values of
      sensitivity and specificity of the Alzheimer's Disease Assessment Scale were
      high. CONCLUSIONS: The Hungarian version of the Alzheimer's Disease Assessment
      Scale was found to be highly reliable and valid and, therefore, the application
      of this scale can be recommended for the establishment of the clinical stage and
      follow-up of patients with Alzheimer's disease. However, the current Hungarian
      version of the Alzheimer's Disease Assessment Scale is not sufficient; the list
      of words and linguistic elements should be selected according to the Hungarian
      standard in the future.

PMID- 22411220
TI  - [Polymyositis-dermatomyositis recognized during the follow-up of a patient with
      type 2 diabetes].
AB  - Polymyositis-dermatomyositis is a rare systemic autoimmune disease which belongs
      to the class of idiopathic inflammatory myopathies. The disease exhibits high
      inter-individual variability, but chronic myositis is a common feature. As
      different manifestations often appear in atypical forms, establishing the precise
      diagnosis can be rather complicated. The prognosis and the patient's life
      expectations highly depend on whether the clinician considers this possibility in
      the diagnostic process or not. The authors present the case of a 50-year-old
      woman who was referred to hospital with suspected myopathy by her general
      practitioner. The history of the patient, the overall clinical picture and some
      marked laboratory abnormalities raised the possibility of polymyositis
      dermatomyositis, which was unequivocally confirmed by immunological tests. Drug
      therapy was started immediately with the administration of high dose
      corticosteroid (1-2 mg/kg/day methylprednisolone), which was found to be an
      effective strategy leading to fast and remarkable improvement in the patient's
      condition. From the first hospital day, the patient also received insulin therapy
      in order to prevent any potential corticosteroid-induced imbalance in her
      carbohydrate metabolism. The long-term patient management was provided by an
      interdisciplinary team the members of which (both clinicians and other health
      care professionals) worked according to a co-ordinated, complex care plan, and
      managed not only the "physiological functions" but the different psychological
      and social problems as well, which are usually associated with the disease. The
      follow-up period of this polyphase disease process lasted for 4.5 years, during
      which only two relapses occurred, and muscle strength typically varied between 3
      and 4 on a five grade scale with the exception of the relapse periods. Good
      outcome was attributed to the strict follow-up and individualized therapy/care.

PMID- 22411222
TI  - [Prime Minister Jozsef Antall remembers Karoly Farkas].

PMID- 22411223
TI  - Serum 25-hydroxyvitamin-D responses to multiple UV exposures from solaria:
      inferences for exposure to sunlight.
AB  - We investigate the relationship between blood serum 25-hydroxyvitamin D (25(OH)D)
      and UV exposure from two artificial sources. We then use the results to test the
      validity of the action spectrum for vitamin D production, and to infer the
      production from summer and winter sunlight. The results are based on a two-arm
      randomised clinical trial of biweekly UV exposure for 12 weeks using two
      different types of dermatological booths: one emitting primarily UV-A radiation,
      and the other emitting primarily UV-B radiation (booth A and booth B
      respectively). In terms of the vitamin D production per unit erythema, one of the
      booths mimics summer noon sunlight, while the other mimics winter noon sunlight.
      Blood samples were taken before and after the exposures. For all participants,
      the phototherapy booth treatments arrested the usual wintertime decline in
      25(OH)D, and for most the treatments from either booth resulted in significant
      increases. The increases were highly non-linear and there was a high degree of
      variability in 25(OH)D and its response to UV from person to person. By the end
      of the 12 week period, the mean increase was >30 nmol l(-1) from a cumulative
      exposure of 17 SED from the UV-A booth, and twice that for the UV-B booth for
      which the cumulative exposure was 268 SED. Assuming a logarithmic relationship
      between UV and vitamin D, the results for the two booths show no obvious
      inconsistency in the action spectrum for pre-vitamin D production. However,
      further measurements with similar exposures from each booth are required to
      confirm its validity. A model was developed to describe the increases in serum
      25(OH)D resulting from the UV exposures, which differed markedly between the two
      booths. The deduced initial rate of increase of 25(OH)D was approximately 5 nmol
      l(-1) per SED. From the large increases in 25(OH)D from each booth, along with
      knowledge of the spectral distribution of sunlight and assuming the currently
      accepted action spectrum for photo-conversion to pre-vitamin D, we infer that the
      production of 25(OH)D from sunlight should be possible throughout the year,
      although in winter the exposures necessary to maintain optimal levels of 25(OH)D
      would be impractically long. This finding is at variance with the commonly-held
      view that no vitamin D is produced at mid-latitudes in the winter. Further work
      is needed to resolve that inconsistency.

PMID- 22411224
TI  - A Lissencephaly-1 homologue is essential for mitotic progression in the planarian
      Schmidtea mediterranea.
AB  - BACKGROUND: Planarians are renowned for their capacity to replace lost tissues
      from adult pluripotent stem cells (neoblasts). Here we report that Lissencephaly
      1 (lis1), which has roles in cellular processes such as mitotic spindle apparatus
      orientation and in signal regulation required for stem cell self-renewal, is
      required for stem cell maintenance in the planarian Schmidtea mediterranea.
      RESULTS: In planarians, lis1 is expressed in differentiated tissues and stem
      cells. lis1 RNAi leads to head regression, ventral curling, and death by lysis.
      By labeling the neoblasts and proliferating cells, we found lis1 knockdown
      animals show a dramatic increase in the number of mitotic cells, followed by
      depletion of the stem cell pool. Analysis of the mitotic spindles in dividing
      neoblasts revealed that defective spindle positioning is correlated with cells
      arrested at metaphase. In addition, we show that inhibiting a planarian homologue
      of nudE, predicted to encode a LIS-1 interacting protein, also leads to cell
      cycle progression defects. CONCLUSIONS: Our results provide evidence for a
      conserved role of LIS1 and NUDE in regulating the function of the mitotic spindle
      apparatus in a representative Lophotrochozoan and that planarians will be useful
      organisms in which to investigate LIS1 regulation of signaling events underlying
      stem cell self-renewal.

PMID- 22411225
TI  - A strategy for the synthesis of mesostructured metal oxides with lower oxidation
      states.
AB  - A detailed study on the pseudomorphic conversion of ordered mesoporous Co(3)O(4)
      and ferrihydrite into CoO and Fe(3)O(4), respectively, by using alcohol/water
      vapor as a gentle reducing agent is described. The reduction conditions for the
      transformation were optimized. In addition, the first one-pot synthesis of
      mesostructured CoO by using nanocasting with cubic ordered silica as a hard
      template is demonstrated.

PMID- 22411226
TI  - Structural transitions and oligomerization along polyalanine fibril formation
      pathways from computer simulations.
AB  - The results of a computer simulation study of the aggregation kinetics of a large
      system of model peptides with particular focus on the formation of intermediates
      are presented. Discontinuous molecular dynamic simulations were used in
      combination with our intermediate-resolution protein model, PRIME, to simulate
      the aggregation of a system of 192 polyalanine (KA(14) K) peptides at a
      concentration of 5 mM and a reduced temperature of T* = 0.13 starting from a
      random configuration and ending in the assembly of a fibrillar structure. The
      population of various structures, including free monomers, beta sheets, amorphous
      aggregates, hybrid aggregates, and fibrils, and the transitions between the
      structures were tracked over the course of 30 independent simulations and
      averaged together. The aggregation pathway for this system starts with the
      association of free monomers into small amorphous aggregates that then grow to
      moderate size by incorporating other free monomers or merging with other small
      amorphous aggregates. These then rearrange into either small beta sheets or
      hybrid aggregates formed by association between unstructured chains and beta
      sheets, both of which grow in size by adding free monomer chains or other small
      aggregates, one at a time. Fibrillar structures are formed initially either by
      the stacking of beta sheets, rearrangement of hybrid aggregates or association
      between beta sheets and hybrid aggregates. They grow by the addition of beta
      sheets, hybrid aggregates, and other small fibrillar structures. The
      rearrangement of amorphous aggregates into beta sheets is a critical and
      necessary step in the fibril formation pathway.

PMID- 22411228
TI  - Midbrain presynaptic dopamine tone predicts sustained and transient neural
      response to emotional salience in humans: fMRI, MEG and FDOPA PET.

PMID- 22411227
TI  - Impairment of synaptic plasticity by the stress mediator CRH involves selective
      destruction of thin dendritic spines via RhoA signaling.
AB  - Stress is ubiquitous in modern life and exerts profound effects on cognitive and
      emotional functions. Thus, whereas acute stress enhances memory, longer episodes
      exert negative effects through as yet unresolved mechanisms. We report a novel,
      hippocampus-intrinsic mechanism for the selective memory defects that are
      provoked by stress. CRH (corticotropin-releasing hormone), a peptide released
      from hippocampal neurons during stress, depressed synaptic transmission, blocked
      activity-induced polymerization of spine actin and impaired synaptic plasticity
      in adult hippocampal slices. Live, multiphoton imaging demonstrated a selective
      vulnerability of thin dendritic spines to this stress hormone, resulting in
      depletion of small, potentiation-ready excitatory synapses. The underlying
      molecular mechanisms required activation and signaling of the actin-regulating
      small GTPase, RhoA. These results implicate the selective loss of dendritic spine
      sub-populations as a novel structural and functional foundation for the
      clinically important effects of stress on cognitive and emotional processes.

PMID- 22411229
TI  - Pandemic influenza A(H1N1) 2009 virus in pregnancy.
AB  - Two hundred fourteen abstracts and 87 full texts regarding pregnant women
      infected with pandemic influenza A(H1N1) 2009 virus were systematically reviewed
      by using a PubMed search and assessing pandemic, clinical, laboratory test,
      vaccine, and control experiences. Both policy and health education were excluded.
      This review counted the total number of pregnant cases from different countries
      and analyzed their epidemic features, including trimester distribution,
      morbidity, hospitalization, intensive care unit admissions, maternal mortality,
      underlying diseases, complications, high-risk factors for death, pregnancy
      outcome, and clinical symptoms compared with the previous pandemic seasonal
      influenza A/H1N1 as compared with the general population. Early identification
      and treatment were the most important factors in different countries and areas
      examined. The vaccine and antiviral drugs that have been the most efficient means
      to control the novel virus appear to be safe but require more extensive study. In
      the future, the focus should be placed on understanding vertical transmission and
      the severe mechanisms.

PMID- 22411230
TI  - Acuted disseminated encephalomyelitis.
AB  - Acute disseminated encephalomyelitis (ADEM) is a disorder of the central nervous
      system (CNS) characterized by an acute event, typically with encephalopathy, in
      which diffuse CNS involvement occurs. It may follow an infectious event and
      occurs more commonly in young children. Pulse steroid treatment is frequently
      used to treat ADEM. Although ADEM is typically described as a benign condition,
      with children generally recovering motor function and resolution of lesions on
      magnetic resonance imaging (MRI), residual cognitive deficits may occur. This
      chapter aims to review the clinical features, typical presentation, differential
      diagnosis, treatment and prognosis of ADEM.

PMID- 22411231
TI  - Age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of irreversible
      blindness in the developed world. Despite recent advances in treatment, AMD
      causes considerable morbidity. For the non-ophthalmologist, a brief background on
      retinal structure is provided, followed by a description of the characteristic
      changes seen in AMD. Subsequently the typical clinical features of AMD are
      discussed with an outline of present management, followed by the current theories
      of AMD pathogenesis. The similarities between AMD and another neurodegenerative
      disease are then highlighted. Finally, we review the on-going clinical trials of
      potential treatments for the future. Since it is clear that multiple risk factors
      are involved in the pathogenesis of AMD, a multi-faceted approach will most
      likely be required in order to prevent further patients progressing to blindness
      as a result of this devastating condition.

PMID- 22411232
TI  - Arachnoid cysts.
AB  - Arachnoid cysts are fluid-filled duplications or splittings of the arachnoid
      layer with a content which is similar but not equal to the cerebrospinal fluid.
      Arachnoid cysts are not actual neurodegenerative disorders, rather the underlying
      defect of the texture of the arachnoid layer is probably congenital in nature.
      They can occur sporadically or can be associated with other malformations or
      diseases. Arachnoid cysts may be discovered in early childhood. However, they can
      develop de novo, grow or decrease in size. They may be diagnosed by ultrasound
      screening in the fetal period or be discovered during childhood or adulthood.
      Many arachnoid cysts are asymptomatic.Treatment strategies are discussed
      controversially. If they are diagnosed incidentally or are correlated with only
      very mild symptoms, a conservative management with follow-up imaging may be
      favored. If they grow, they can cause headaches, seizures or other neurological
      symptoms and require neurosurgical treatment. This chapter addresses aspects of
      pathogenesis, clinical symptoms, indication for neurosurgical treatment and
      treatment options.

PMID- 22411233
TI  - Autism spectrum disorders: information for pediatricians supporting families of
      young children on the spectrum.
AB  - Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder affecting in US 1
      in 110 individuals.(1) As increasingly younger children are receiving ASD
      diagnoses, many pediatricians are now faced with the unique needs of parents and
      other caregivers of newly diagnosed toddlers and young children. This chapter
      provides an overview of ASD designed to offer information and resources to
      pediatricians that could, in turn, be provided to families of children newly
      diagnosed with ASD.

PMID- 22411234
TI  - Autosomal recessive Charcot-Marie-Tooth neuropathy.
AB  - Charcot-Marie-Tooth (CMT) disease, a hereditary motor and sensory neuropathy that
      comprises a complex group of more than 50 diseases, is the most common inherited
      neuropathy. CMT is generally divided into demyelinating forms, axonal forms and
      intermediate forms. CMT is also characterized by a wide genetic heterogeneity
      with 29 genes and more than 30 loci involved. The most common pattern of
      inheritance is autosomal dominant (AD), although autosomal recessive (AR) forms
      are more frequent in Mediterranean countries. In this chapter we give an overview
      of the associated genes, mechanisms and epidemiology of AR-CMT forms and their
      associated phenotypes.

PMID- 22411235
TI  - Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease (CJD), a neurodegenerative disorder that is the
      commonest form of human prion disease or transmissible spongiform
      encephalopathies (TSEs). Four types of CJD are known: Sporadic (sCJD), familial
      or genetic (gCJD); iatrogenic (iCJD) and variant CJD (vCJD). The latter results
      from transmission of bovine spongiform encephalopathy (BSE) from cattle to
      humans. The combination of PrP(Sc) peptide (either 21 kDa or 19 kDa) and the
      status of the codon 129 of the gene (PRNP) encoding for PrP (either Methionine or
      Valine) is used to classify sCJD into 6 types: MM1 and MV1, the most common; VV2;
      MV2 (Brownell/Oppenheimer syndrome); MM2; VV1 and sporadic fatal insomnia, in
      that order of prevalence. Genetic CJD is caused by diverse mutations in the PRNP
      gene. The neuropathology of CJD consists of spongiform change, astro- and
      microgliosis and poorly defined neuronal loss. In a proportion of cases, amyloid
      plaques, like those of kuru, are seen. PrP immunohistochemistry reveals different
      types of PrP(Sc) deposits - the most common is the synaptic-type, but
      perivacuolar, perineuronal and plaque-like deposits may be also detected.

PMID- 22411236
TI  - Epigenetics in autism and other neurodevelopmental diseases.
AB  - Autism was previously thought to be caused by environmental factors. However,
      genetic factors are now considered to be more contributory to the pathogenesis of
      autism, based on the recent findings of mutations in the genes which encode
      synaptic molecules associated with the communication between neurons. Epigenetic
      is a mechanism that controls gene expression without changing DNA sequence but by
      changing chromosomal histone modifications and its abnormality is associated with
      several neurodevelopmental diseases. Since epigenetic modifications are known to
      be affected by environmental factors such as nutrition, drugs and mental stress,
      autistic diseases are not only caused by congenital genetic defects, but may also
      be caused by environmental factors via epigenetic mechanism. In this chapter, we
      introduce autistic diseases caused by epigenetic failures and discuss epigenetic
      changes by environmental factors and discuss new treatments for
      neurodevelopmental diseases based on the recent epigenetic findings.

PMID- 22411237
TI  - Epilepsy and epileptic syndrome.
AB  - Epilepsy is one of the most common neurological disorders. In most patients with
      epilepsy, seizures respond to available medications. However, a significant
      number of patients, especially in the setting of medically-intractable
      epilepsies, may experience different degrees of memory or cognitive impairment,
      behavioral abnormalities or psychiatric symptoms, which may limit their daily
      functioning. As a result, in many patients, epilepsy may resemble a
      neurodegenerative disease. Epileptic seizures and their potential impact on brain
      development, the progressive nature of epileptogenesis that may functionally
      alter brain regions involved in cognitive processing, neurodegenerative processes
      that relate to the underlying etiology, comorbid conditions or epigenetic
      factors, such as stress, medications, social factors, may all contribute to the
      progressive nature of epilepsy. Clinical and experimental studies have addressed
      the pathogenetic mechanisms underlying epileptogenesis and neurodegeneration.We
      will primarily focus on the findings derived from studies on one of the most
      common causes of focal onset epilepsy, the temporal lobe epilepsy, which indicate
      that both processes are progressive and utilize common or interacting pathways.
      In this chapter we will discuss some of these studies, the potential candidate
      targets for neuroprotective therapies as well as the attempts to identify early
      biomarkers of progression and epileptogenesis, so as to implement therapies with
      early-onset disease-modifying effects.

PMID- 22411238
TI  - Frontotemporal Lobar Degeneration.
AB  - Frontotemporal Lobar Degeneration (FTLD) is an heterogeneous neurodegenerative
      disorder characterized by behaviour and language disturbances, associated with
      degeneration of the frontal and temporal lobes. Three different clinical
      presentations have been described, namely behavioural variant Frontotemporal
      Dementia (bvFTD), Semantic Dementia (SD) and Progressive Non-Fluent Aphasia
      (PNFA). The associated histopathology includes different neuropathological
      hallmarks, the most frequent being tau-positive inclusions (FTLD-TAU) or tau
      negative and TDP-43 positive inclusions (FTLD-TDP). The majority of familial FTLD
      cases are caused by mutations within Microtubule-Associated Protein Tau (MAPT)
      gene, leading to FTLD-TAU, or Progranulin (PGRN) gene, leading to FTLD-TDP. In
      the last few years, imaging, biological and genetic biomarkers have been
      developed, helping in clinical evaluation and diagnostic accuracy. Though current
      pharmacologic interventions are only symptomatic, recent research argues for
      possible disease-modifying strategies in the near future.

PMID- 22411239
TI  - Gerstmann-Straussler-Scheinker disease.
AB  - Gerstmann-Straussler-Scheinker (GSS) is a slowly progressive hereditary autosomal
      dominant disease (OMIM: 137440) and the first human transmissible spongiform
      encephalopathy (TSE) in which a mutation in a gene encoding for prion protein
      (PrP) was discovered. The first "H" family had been known by the Viennese
      neuropsychiatrists since the XXth century and was reported by Gerstmann,
      Straussler and Scheinker in 1936. In this chapter we present the clinical,
      neuropathological and molecular data on GSS with the mutations in the PRNP gene:
      at codons 102, 105, 117, 131, 145, 187, 198, 202, 212, 217 and 232. In several
      families with GSS the responsible mutations are unknown.

PMID- 22411240
TI  - Juvenile neuronal ceroid lipofuscinoses.
AB  - Juvenile neuronal ceroid lipofuscinoses (JNCL) is the most common type of the
      neuronal ceroid lipofuscinoses (NCLs), a group of pediatric neurodegenerative
      diseases. In this chapter the genetic and biochemical basis, pathogenesis,
      clinical features, histopathological features, diagnosis and therapeutic
      strategies of the JNCL are reviewed. The premature death of the patients and
      subnormal life quality are inevitable due to the lack of understanding of
      pathogenesis and limitation in treatment. Hence we are still a long way to
      conquer the disease.

PMID- 22411241
TI  - Kuru: the first prion disease.
AB  - Kuru disease is linked with the name of D. Carleton Gajdusek and he was the first
      to show that this human neurodegenerative disease can be transmitted to
      chimpanzees and subsequently classified as a transmissible spongiform
      encephalopathy (TSE), or slow unconventional virus disease. It was first reported
      to Western world in 1957 by Gajdusek and Vincent Zigas,(1,2) and in 1975 a
      complete bibliography of kuru was published by Alpers et al.(3) "Kuru" in the
      Fore language in Papua New Guinea means to shiver from fever and cold. The
      disease has been found to spread through ritualistic cannibalism and is an
      invariably fatal cerebellar ataxia accompanied by tremor, choreiform and athetoid
      movements. Neuropathologically, kuru is characterized by the presence of amyloid
      "kuru" plaques.

PMID- 22411242
TI  - Leukodystrophies.
AB  - Leukodystrophies comprise a broad group of progressive, inherited disorders
      affecting mainly myelin. They often present after a variable period of normalcy
      with a variety of neurologic problems. Though the ultimate diagnosis is not found
      in many patients with leukodystrophies, distinctive features unique to them aid
      in diagnosis, treatment and prognostication. The clinical characteristics,
      etiologies, diagnostic testing and treatment options are reviewed in detail for
      some of the major leukodystrophies: X-linked adrenoleukodystrophy, Krabbe
      disease, metachromatic leukodystrophy, Pelizaeus-Merzbacher disease, Alexander
      disease, Canavan disease, megalencephalic leukoencephalopathy with subcortical
      cysts and vanishing white matter disease.

PMID- 22411243
TI  - Machado-Joseph disease and other rare spinocerebellar ataxias.
AB  - The spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases
      characterised by progressive lack of motor coordination leading to major
      disability. SCAs show high clinical, genetic, molecular and epidemiological
      variability. In the last one decade, the intensive scientific research devoted to
      the SCAs is resulting in clear advances and a better understanding on the genetic
      and nongenetic factors contributing to their pathogenesis which are facilitating
      the diagnosis, prognosis and development of new therapies. The scope of this
      chapter is to provide an updated information on Machado-Joseph disease (MJD), the
      most frequent SCA subtype worldwide and other rare spinocerebellar ataxias
      including dentatorubral-pallidoluysian atrophy (DRPLA), the X-linked fragile X
      tremor and ataxia syndrome (FXTAS) and the nonprogressive episodic forms of
      inherited ataxias (EAs). Furthermore, the different therapeutic strategies that
      are currently being investigated to treat the ataxia and non-ataxia symptoms in
      SCAs are also described.

PMID- 22411244
TI  - Neurodegenerations induced by organophosphorous compounds.
AB  - Organophosphorous compounds (OPs) are widely used in agriculture, industry and
      the home. Though best known for their acute effects when used as pesticides,
      which target acetylcholinesterase (AChE) activity in neuromuscular junctions and
      the central nervous system, not all OPs are potent inhibitors of this enzyme. The
      widespread use of OPs has heightened concern regarding their toxicity in man,
      with numerous reports linking OPs to various forms of delayed neuropathy
      encompassing a range of neurodegenerative, psychological and neurobehavioral
      effects. There is mounting evidence to suggest that sub-acute levels of OPs have
      the ability to interact directly with a range of target proteins in addition to
      AChE (i.e., noncholinergic targets), causing major disruption of membrane and
      protein turnover, protein phosphorylation, mitochondrial dysfunction, oxidative
      stress and cytoskeletal re-organisation, although the mechanisms involved are not
      fully understood. However, major advances have been made in the study of one OP
      binding protein neuropathy target esterase (NTE) in terms of its true
      physiological role. Additionally, there is increasing evidence for the ability of
      OPs to cause disruption in a number of metabolic and cell signalling pathways
      that affect neuronal cell proliferation, differentiation and survival and to
      interact direct with non-esterase proteins such as tubulin. The aim of this
      chapter is to review our current understanding of delayed neurotoxicity, to
      discuss how these molecular events may relate to each other and to suggest
      possible future directions in mechanistic studies of OP toxicity.

PMID- 22411245
TI  - Mitochondrial importance in Alzheimer's, Huntington's and Parkinson's diseases.
AB  - Mitochondria have been long known as "gatekeepers of life and death". Indeed,
      these dynamic organelles are the master coordinators of energy metabolism, being
      responsible for the generation of the majority of cellular ATP. Notably,
      mitochondria are also one of the primary producers of intracellular reactive
      oxygen species which are the main inducer of oxidative damage. Neurons, as
      metabolically active cells with high energy demands, are predominantly dependent
      on mitochondrial function, as reflected by the observation that mitochondrial
      defects are key features of chronic neurodegenerative diseases. Indeed,
      morphologic, biochemical and molecular genetic studies posit that mitochondria
      constitute a convergence point for neurodegeneration. Moreover, recent findings
      convey that neurons are particularly reliant on the dynamic properties of
      mitochondria, further emphasizing the critical role of mitochondria in neuronal
      functions. This chapter highlights how mitochondrial pathobiology might
      contribute to neurodegeneration in Alzheimer's, Parkinson's and Huntington's
      diseases.

PMID- 22411246
TI  - Multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic, complex neurological disease with a
      variable clinical course in which several pathophysiological mechanisms such as
      axonal/ neuronal damage, demyelination, inflammation, gliosis, remyelination and
      repair, oxidative injury and excitotoxicity, alteration of the immune system as
      well as biochemical disturbances and disruption of blood-brain barrier are
      involved.(1,2) Exacerbations of MS symptoms reflect inflammatory episodes, while
      the neurodegenerative aspects of gliosis and axonal loss result in the
      progression of disability. The precise aetiology of MS is not yet known, although
      epidemiological data indicate that it arises from a complex interactions between
      genetic susceptibility and environmental factors.(3) In this chapter the brain
      structures and processes involved in immunopathogenesis of MS are presented.
      Additionally, clinical phenotypes and biomarkers of MS are showed.

PMID- 22411247
TI  - Myotonic Dystrophy Type 1 or Steinert's disease.
AB  - Myotonic Dystrophy Type 1 (DM1) is the most common worldwide autosomal dominant
      muscular dystrophy due to polynucleotide [CTG]( n ) triplet expansion located on
      the 3'UTR of chromosome 19q13.3. A toxic gain-of-function of abnormally stored
      RNA in the nuclei of affected cells is assumed to be responsible for several
      clinical features of the disease. It plays a basic role in deregulating RNA
      binding protein levels and in several mRNA splicing processes of several genes,
      thus leading to the multisystemic features typical of DM1. In DM1, the
      musculoskeletal apparatus, heart, brain, eye, endocrine, respiratory and
      gastroenteric systems are involved with variable levels of severity. DM1 onset
      can be congenital, juvenile, adult or late. DM1 can be diagnosed on the grounds
      of clinical presentation (distal muscular atrophy and weakness, grip and
      percussion myotonia, ptosis, hatchet face, slurred speech, rhinolalia), EMG
      myotonic pattern, EKG (such as AV-blocks) or routine blood test abnormalities
      (such as increased CK values or hypogamma-globulinemia) and history of cataract.
      Its confirmation can come by DNA analysis. At present, only symptomatic therapy
      is possible and is addressed at correcting hormonal and glycemic balance,
      removing cataract, preventing respiratory failure and, above all, major cardiac
      disturbances. Efficacious therapies targeted at the pathogenic mechanism of DM1
      are not yet available, while studies that seek to block toxic RNA intranuclear
      storage with specific molecules are still ongoing.

PMID- 22411248
TI  - Neurodegeneration in diabetes mellitus.
AB  - Diabetes mellitus is recognized as a group of heterogeneous disorders with the
      common elements of hyperglycaemia and glucose intolerance due to insulin
      deficiency, impaired effectiveness of insulin action, or both. The prevalence of
      Type 2 diabetes mellitus (T2DM) increases with age and dementia also increases
      its incidence in later life. Recent studies have revealed that T2DM is a risk
      factor for cognitive dysfunction or dementia, especially those related to
      Alzheimer's disease (AD). Insulin resistance, which is often associated with
      T2DM, may induce a deficiency of insulin effects in the central nervous system
      (CNS). Insulin may have a neuroprotective role and may have some impact on
      acetylcholine (ACh) synthesis. Hyperinsulinemia, induced by insulin resistance
      occurring in T2DM, may be associated with insulin deficiency caused by reduced
      insulin transport via the blood brain barrier (BBB). Insulin has multiple
      important functions in the brain. Some basic research, however, suggests that
      insulin accelerates Alzheimer-related pathology through its effects on the
      amyloid beta (Abeta) metabolism and tau phosphorylation.Asymptomatic ischemic
      lesions in T2DM subjects may lower the threshold for the development of dementia
      and this may explain the inconsistency between the basic research and
      clinicopathological studies.More research to elucidate the mechanism of
      neurodegeneration associated with T2DM is warranted.

PMID- 22411249
TI  - Neurofibromatoses.
AB  - The studies of familial tumor predisposition syndromes have contributed immensely
      to our understanding of oncogenesis. Neurofibromatosis 1, neurofibromatosis 2 and
      schwannomatosis are inherited autosomal dominant neurocutaneous disorders with
      complete penetrance. They are clinically and genetically distinct and
      considerable knowledge has been gathered about their pathogenesis. In this
      chapter, the genetics, molecular mechanism of disease, as well as clinical
      features, diagnosis and treatment are discussed.

PMID- 22411250
TI  - Oxidative stress in developmental brain disorders.
AB  - In order to examine the involvement of oxidative stress in developmental brain
      disorders, we have performed immunohistochemistry in autopsy brains and enzyme
      linked immunosorbent assay (ELISA) in the cerebrospinal fluid and urines of
      patients. Here, we review our data on the hereditary DNA repair disorders,
      congenital metabolic errors and childhood-onset neurodegenerative disorders.
      First, in our studies on hereditary DNA repair disorders, increased oxidative DNA
      damage and lipid peroxidation were carried out in the degeneration of basal
      ganglia, intracerebral calcification and cerebellar degeneration in patients with
      xeroderma pigmentosum, Cockayne syndrome and ataxia-telangiectasia-like disorder,
      respectively. Next, congenital metabolic errors, apoptosis due to lipid
      peroxidation seemed to cause neuronal damage in neuronal ceroid-lipofuscinosis.
      Oxidative stress of DNA combined with reduced expression of antioxidant enzymes
      occurred in the lesion of the cerebral cortex in mucopolysaccharidoses and
      mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes.
      In childhood-onset neurodegenerative disorders, increased oxidative DNA damage
      and lipid peroxidation may lead to motor neuron death in spinal muscular atrophy
      like in amyotrophic lateral sclerosis. In patients with dentatorubral
      pallidoluysian atrophy, a triplet repeat disease, deposition of oxidative
      products of nucleosides and reduced expression of antioxidant enzymes were found
      in the lenticular nucleus. In contrast, the involvement of oxidative stress is
      not definite in patients with Lafora disease. Rett syndrome patients showed
      changes of oxidative stress markers and antioxidant power in urines, although the
      changes may be related to systemic complications.

PMID- 22411251
TI  - Oxidative stress and mitochondrial dysfunction in Down syndrome.
AB  - Down syndrome (DS) or trisomy 21 is the genetic disease with highest prevalence
      displaying phenotypic features that both include neurologic deficiencies and a
      number of clinical outcomes. DS-associated neurodegeneration recalls the clinical
      course of Alzheimer disease (AD), due to DS progression toward dementia and
      amyloid plaques reminiscent of AD clinical course. Moreover, DS represents one of
      the best documented cases of a human disorder aetiologically related to the redox
      imbalance that has long been attributed to overexpression of Cu,Zn-superoxide
      dismutase (SOD-1), encoded by trisomic chromosome 21. The involvement of
      oxidative stress has been reported both in genes located else than at chromosome
      21 and in transcriptional regulation of genes located at other chromosomes.
      Another well documented hallmark of DS phenotype is represented by a set of
      immunologic defects encompassing a number of B and T-cell functions and cytokine
      production, together prompting a proinflammatory state. In turn, this condition
      can be directly interrelated with an in vivo prooxidant state. As an essential
      link to oxidative stress, mitochondrial dysfunctions are observed whenever redox
      imbalances occur, due to the main roles of mitochondria in oxygen metabolism and
      this is the case for DS. Ultrastructural and biochemical abnormalities were
      reported in mitochondria from human DS patients and from trisomy 16 (Ts16) mice,
      to be reviewed in this chapter. Together, in vivo alterations of mitochondrial
      function are consistent with a prooxidant state as a phenotypic hallmark in DS.

PMID- 22411252
TI  - Pick's disease.
AB  - Picks disease is a major clinicopathological disease having circumscribed atrophy
      in the frontotemporal lobe. Demented patients with frontotemporal atrophy are now
      clinically diagnosed as frontotemporal lobar degeneration (FTLD). Other
      underlying pathologies in patients with FTLD include FTLD with TDP-43-positive
      inclusions, corticobasal degeneration, progressive supranuclear palsy, basophilic
      inclusion body disease, neuronal intermediate filament inclusion disease and
      argyrophilic grain disease. In this chapter, recent findings regarding the
      distinct clinical and histopathological features of these pathological disease
      entities are presented including the discussion on the possibility of future
      antemortem diagnosis of patients with the disease.In this chapter, recent
      findings regarding the distinct clinical and histopathological features of these
      pathological disease entities are presented including the discussion on the
      possibility of future antemortem diagnosis of patients with the disease.

PMID- 22411253
TI  - Premature aging syndrome.
AB  - Hutchinson-Gilford progeria syndrome and Werner syndrome are two of the best
      characterized human progeroid diseases with clinical features mimicking
      physiological aging at an early age. Both disorders have been the focus of
      intense research in recent years since they might provide insights into the
      pathology of normal human aging. The chapter contains a detailed description of
      the clinical features of both disorders and then it focuses on the genetics, the
      resulting biochemical alterations at the protein level and the most recent
      findings and hypotheses concerning the molecular basis of the premature aging
      phenotypes. A description of available diagnostic and therapeutic approaches is
      included.

PMID- 22411254
TI  - The savant syndrome and its possible relationship to epilepsy.
AB  - The goal of this chapter is to review the Savant syndrome (SS), characterized by
      outstanding islands of mental ability in otherwise handicapped individuals. Two
      forms exist: The congenital and acquired form. Among the many examples of the
      congenital form are the calendar calculators, who can quickly provide the day of
      the week for any date in the past. Other examples are the musical savants with
      perfect pitch and the hyperlexics, who (in one case) can read a page in 8 seconds
      and recall the text later at a 99% level. Other types of talents and artistic
      skills can be found, involving 3-D drawing, map memory, poetry, painting,
      sculpturing, including one savant who could recite without error the value of Pi
      to 22,514 places. The acquired form refers to the development of outstanding
      skills after some brain injury or disease, usually involving the left fronto
      temporal area. This type of injury seems to inhibit the 'tyranny of the left
      hemisphere', allowing the right hemisphere to develop the savant skills. One
      other way to inhibit the left fronto-temporal area is to use transcranial
      magnetic stimulation in normal subjects and nearly one-half of these subjects can
      then perform new skills during the stimulation that they could not perform
      before. This type of finding indicates the potentiality in all of us for the
      development of savant skills under special circumstances. Explanations of the
      congenital SS include enhanced local connectivity as a compensation for
      underconnectivity of long-range fibers, but also weak central coherence, replaced
      by great attention to details, enhanced perceptual functioning and obsessive pre
      occupation with specific interests. Neurodegenerative Diseases, edited by Shamim
      I. Ahmad.

PMID- 22411255
TI  - Sjogren-Larsson syndrome.
AB  - Sjogren-Larsson syndrome is a rare disease characterized by the occurrence of
      mental retardation, spastic diplegia and ichthyosis. The involvement of brain and
      skin is justified by a mutation in FALDH gene that affects the metabolism of
      fatty acids and leads to abnormal accumulation of lipids. The normal formation of
      multilamellar membranes in the stratum corneum and myelin is impaired. The aim of
      this chapter is to review the classical manifestation of the disease and its
      differential diagnosis.

PMID- 22411256
TI  - The spinocerebellar ataxias: clinical aspects and molecular genetics.
AB  - Spinocerebellar ataxias (SCAs) are a highly heterogeneous group of inherited
      neurological disorders, based on clinical characterization alone with variable
      degrees of cerebellar ataxia often accompanied by additional cerebellar and
      noncerebellar symptoms which in most cases defy differentiation. Molecular
      causative deficits in at least 31 genes underlie the clinical symptoms in the
      SCAs by triggering cerebellar and, very frequently, brain stem dysfunction. The
      identification of the causative molecular deficits enables the molecular
      diagnosis of the different SCA subtypes and facilitates genetic counselling.
      Recent scientific advances are shedding light into developing therapeutic
      strategies. The scope of this chapter is to provide updated details of the
      spinocerebellar ataxias with particular emphasis on those aspects aimed at
      facilitating the clinical and genetic diagnoses.

PMID- 22411257
TI  - Tourette syndrome.
AB  - Tourette syndrome (TS) is a neurodevelopmental disorder consisting of multiple
      motor and one or more vocal/phonic tics. TS is increasingly recognized as a
      common neuropsychiatric disorder usually diagnosed in early childhood and
      comorbid neuropsychiatric disorders occur in approximately 90% of patients, with
      attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder
      (OCD) being the most common ones. Moreover, a high prevalence of depression and
      personality disorders has been reported. Although the mainstream of tic
      management is represented by pharmacotherapy, different kinds of psychotherapy,
      along with neurosurgical interventions (especially deep brain stimulation, DBS)
      play a major role in the treatment of TS. The current diagnostic systems have
      dictated that TS is a unitary condition. However, recent studies have
      demonstrated that there may be more than one TS phenotype. In conclusion, it
      appears that TS probably should no longer be considered merely a motor disorder
      and, most importantly, that TS is no longer a unitary condition, as it was
      previously thought.

PMID- 22411258
TI  - Biological aging alters circadian mechanisms in murine adipose tissue depots.
AB  - Biological aging alters the metabolism and volume of adipose tissue depots.
      Recent evidence suggests that circadian mechanisms play a role in promoting
      adipogenesis, obesity, and lipodystrophy. The current study compared cohorts of
      younger (5-9 months) and older (24-28 months) C57BL/6 mice as a function of
      biological age and circadian time. Advanced age significantly reduced the weight
      of the brown, epididymal, inguinal, and retroperitoneal adipose depots but not
      total body weight. The older mice reduced their physical activity by >50% and
      delayed their activity initiation after light offset. The expressed transcriptome
      in brown and white adipose depots and liver of both cohorts displayed evidence of
      circadian rhythmicity; however, the oscillating mRNAs differed significantly
      between age groups and across tissues. The amplitude of Cry1, a component of the
      negative arm of the circadian apparatus, and downstream regulators such as Rev
      erbalpha were elevated in the older relative to the younger cohorts as a function
      of circadian time. Overall, transcript levels differed significantly for 557
      (inguinal adipose), 1,016 (liver), and 1,021 (brown adipose) expressed sequences
      between the cohorts as a function of age. These included transcripts encoding
      proteins within the canonical and non-canonical Wnt pathways. Since the Wnt
      pathway regulates adipose stem cell differentiation and shares a critical enzyme,
      glycogen synthase kinase 3beta, with the circadian mechanism, the intersection
      between these two fundamental regulatory mechanisms merits further investigation
      with respect to biological aging of adipose tissues.

PMID- 22411259
TI  - Melatonin can improve insulin resistance and aging-induced pancreas alterations
      in senescence-accelerated prone male mice (SAMP8).
AB  - The aim of the present study was to investigate the effect of aging on several
      parameters related to glucose homeostasis and insulin resistance in pancreas and
      how melatonin administration could affect these parameters. Pancreas samples were
      obtained from two types of male mice models: senescence-accelerated prone (SAMP8)
      and senescence-accelerated-resistant mice (SAMR1). Insulin levels in plasma were
      increased with aging in both SAMP8 and SAMR1 mice, whereas insulin content in
      pancreas was decreased with aging in SAMP8 and increased in SAMR1 mice.
      Expressions of glucagon and GLUT2 messenger RNAs (mRNAs) were increased with
      aging in SAMP8 mice, and no differences were observed in somatostatin and insulin
      mRNA expressions. Furthermore, aging decreased also the expressions of Pdx-1,
      FoxO 1, FoxO 3A and Sirt1 in pancreatic SAMP8 samples. Pdx-1 was decreased in
      SAMR1 mice, but no differences were observed in the rest of parameters on these
      mice strains. Treatment with melatonin was able to decrease plasma insulin levels
      and to increase its pancreatic content in SAMP8 mice. In SAMR1, insulin
      pancreatic content and plasma levels were decreased. HOMA-IR was decreased with
      melatonin treatment in both strains of animals. On the other hand, in SAMP8 mice,
      treatment decreased the expression of glucagon, GLUT2, somatostatin and insulin
      mRNA. Furthermore, it was also able to increase the expression of Sirt1, Pdx-1
      and FoxO 3A. According to these results, aging is associated with significant
      alterations in the relative expression of pancreatic genes associated to glucose
      metabolism. This has been especially observed in SAMP8 mice. Melatonin
      administration was able to improve pancreatic function in old SAMP8 mice and to
      reduce HOMA-IR improving their insulin physiology and glucose metabolism.

PMID- 22411260
TI  - Clinical evaluation of the performance and safety of a new dentine substitute,
      Biodentine, in the restoration of posterior teeth - a prospective study.
AB  - OBJECTIVES: A multicentric randomized, 3-year prospective study was conducted to
      determine for how long Biodentine, a new biocompatible dentine substitute, can
      remain as a posterior restoration. MATERIALS AND METHODS: First, Biodentine was
      compared to the composite Z100(r), to evaluate whether and for how long it could
      be used as a posterior restoration according to selected United States Public
      Health Service (USPHS)' criteria (mean +/- SD). Second, when abrasion occurred,
      Biodentine was evaluated as a dentine substitute combined with Z100(r). RESULTS:
      A total of 397 cases were included. This interim analysis was conducted on 212
      cases that were seen for the 1-year recall. On the day of restoration placement,
      both materials obtained good scores for material handling, anatomic form (0.12 +/
      0.33), marginal adaptation (0.01 +/- 0.10) and interproximal contact (0.11 +/-
      0.39). During the follow-up, both materials scored well in surface roughness
      (<=1) without secondary decay and post-operative pain. Biodentine kept acceptable
      surface properties regarding anatomic form score (<=1), marginal adaptation score
      (<=2) and interproximal contact score (<=1) for up to 6 months after placement.
      Resistance to marginal discoloration was superior with Biodentine compared to
      Z100(r). When Biodentine was retained as a dentine substitute after pulp vitality
      control, it was covered systematically with the composite Z100(r). This procedure
      yielded restorations that were clinically sound and symptom free. CONCLUSIONS:
      Biodentine is able to restore posterior teeth for up to 6 months. When
      subsequently covered with Z100(r), it is a convenient, efficient and well
      tolerated dentine substitute. CLINICAL RELEVANCE: Biodentine as a dentine
      substitute can be used under a composite for posterior restorations.

PMID- 22411261
TI  - In vitro comparison of mechanical properties and degree of cure of bulk fill
      composites.
AB  - OBJECTIVES: The aim of our study was to measure and compare degree of conversion
      (DC) as well as micro- (indentation modulus, E; Vickers hardness, HV) and
      macromechanical properties (flexural strength, sigma; flexural modulus, E
      (flexural)) of two recently launched bulk fill resin-based composites (RBCs):
      Surefil(r) SDRTM flow (SF) and Venus(r) bulk fill (VB). MATERIALS AND METHODS: DC
      (n = 6) was investigated by Fourier transform infrared spectroscopy (FTIR) in
      clinical relevant filling depths (0.1, 2, and 4 mm; 6 mm bulk, 6 mm incremental)
      and irradiation times (10, 20, 40 s). Micro- (n = 6) and macromechanical (n = 20)
      properties were measured by an automatic microhardness indenter and a three-point
      bending test device after storing the specimens in distilled water for 24 h at 37
      degrees C. Furthermore, on the 6-mm bulk samples, the depth of cure was
      determined. A field emission scanning electron microscope was used to assess
      filler size. Results were evaluated using one-way analysis of variance, Tukey's
      honest significance test post hoc test, a multivariate analysis (alpha = 0.05)
      and an independent t test. Weibull analysis was used to assess sigma. RESULTS: VB
      showed, in all depth, significant higher DC (VB, 62.4-67.4 %; SF, 57.1-61.9 %),
      but significant lower macro- (VB, E (flexural) = 3.6 GPa; sigma = 122.7 MPa; SF,
      E (flexural) = 5.0 GPa; sigma = 131.8 MPa) and micromechanical properties (VB, E
      = 7.3-8.8 GPa, HV = 40.7-46.5 N/mm2; SF, E = 10.6-12.2 GPa, HV = 55.1-61.1
      N/mm2). Both RBCs showed high reliability (VB, m = 21.6; SF, m = 26.7) and a
      depth of cure of at least 6 mm at all polymerization times. The factor "RBC"
      showed the strongest influence on the measured properties (eta (2) = 0.35-0.80)
      followed by "measuring depth" (eta (2) = 0.10-0.46) and "polymerization time"
      (eta (2) = 0.03-0.12). CONCLUSIONS: Significant differences between both RBCs
      were found for DC, E, sigma, and E (flexural) at all irradiation times and
      measuring depths. CLINICAL RELEVANCE: Curing the RBCs in 4-mm bulks for 20 s can
      be recommended.

PMID- 22411262
TI  - Comparison of cone-beam and conventional multislice computed tomography for image
      guided dental implant planning.
AB  - OBJECTIVES: To compare the accuracy of cone-beam CT (CBCT) and multislice CT
      (MSCT) with regard to its use in image-guided dental implant surgery in a
      prospective model based study. MATERIAL AND METHODS: Ten photopolymer-acrylate
      mandibula models, each with four precise metal reference markers, were scanned
      with MSCT and CBCT. The six reference distances between the markers were measured
      by a three-axis milling machine first. The distances were then measured by (1)
      navigation with the Medtronic StealthStation(r) TREONTM image-guided surgery
      system, (2) with the Medtronic planning-tool and (3) on the PC with the Mimics(r)
      software. Mean values were calculated for all three methods for CBCT and MSCT and
      were compared for statistical significance. RESULTS: Of all measurements, 83% of
      the arithmetic mean values were within the +/-0.5 mm range (MSCT 88% and CBCT
      78%) and 17% within the +/-1.0 mm range (MSCT 12% and CBCT 22%). The absolute
      difference of the arithmetic mean values showed no statistically significant
      difference between MSCT and CBCT. The difference of the overall mean values to
      the reference was 0.43 mm for MSCT and 0.46 mm for CBCT. CONCLUSIONS: The data of
      our study prove that the application of CBCT for the indicated purpose yielded
      good results comparable to those of MSCT. All three measuring methods were
      feasible and accuracy was statistically not different between the data acquired
      by MSCT and CBCT within the setting of this study.

PMID- 22411263
TI  - The effect of aging on the mechanical properties of nanohybrid composites based
      on new monomer formulations.
AB  - OBJECTIVES: Nanohybrid resin-based composites (RBCs) containing new types of
      matrix monomers such as dimer acid-based dimethacrylate or tricyclodecane
      urethane are assumed to show decreased water uptake and therefore better
      resistance to hydrolytic degradation than RBCs using bisphenol A diglycidyl
      methacrylate (BisGMA) due to their hydropobic nature. Our study aimed to analyze
      the effect of aging on six nanohybrid RBCs, of which two are using these new
      types of monomers, with regard to differences in the mechanical properties of the
      materials. MATERIALS AND METHODS: Diametral tensile strength (DTS), Vickers
      hardness (HV), and creep were measured. Mechanical tests were performed after
      storing samples for 24 h in distilled water, as well as after aging
      (thermocycling for 5,000 cycles at 5-55 degrees C and storage for 4 weeks either
      in distilled water, artificial saliva, or ethanol). RESULTS: The effect of aging
      on all test parameters was lower than the effect of the material. This
      information was provided by a general linear model, showing higher partial eta(2)
      values for the influence factor material than for the factor aging. The influence
      of aging on the micromechanical properties HV and creep was proven to be more
      sensitive than on the macromechanical property (DTS). This was also illustrated
      by lower eta(2) values for the variable aging for DTS. An increase of the creep
      of all materials was observed after storage in alcohol. CONCLUSIONS: The use of
      new types of monomers could not be shown to be a significant advantage to the
      other examined materials containing BisGMA. CLINICAL RELEVANCE: Nanohybrid
      composites can be recommended as universal filling materials, whether based on
      new or conventional monomers.

PMID- 22411264
TI  - EACTS guidelines for the use of patient safety checklists.
AB  - The Safety Checklist concept has been an integral part of many industries that
      face high-complexity tasks for many decades and in industries such as aviation
      and engineering checklists have evolved from their very inception. Investigations
      of the causes of surgical deaths around the world have repeatedly pointed to
      medical errors that could be prevented as an important cause of death and
      disability. As a result, the World Health Organisation developed and evaluated a
      three-stage surgical checklist in 2007 demonstrating that complications were
      significantly reduced, including surgical infection rates and even mortality.
      Together with the results from other large cohort studies into the utility of the
      surgical checklist, many countries have fully implemented the use of surgical
      checklists into routine practice. A key factor in the successful implementation
      of a surgical checklist is engagement of the staff implementing the checklist. In
      surgical specialties such as our own it was quickly seen that there were many
      important omissions in the generic checklist that did not cover issues particular
      to our specialty, and thus the European Association for Cardio-Thoracic Surgery
      embarked on a process to create a version of the checklist that might be more
      appropriate and specific to cardiothoracic surgery, including checks on
      preparations for excessive bleeding, perfusion arrangements and ICU preparations,
      for example. The guideline presented here summarizes the evidence for the
      surgical checklist and also goes through in detail the changes recommended for
      our specialty.

PMID- 22411265
TI  - Detecting biochemical changes in the rodent cervix during pregnancy using Raman
      spectroscopy.
AB  - The goal of this research is to determine whether Raman spectroscopy (RS), an
      optical method that probes the vibrational modes of tissue components, can be
      used in vivo to study changes in the mouse cervix during pregnancy. If
      successful, such a tool could be used to detect cervical changes due to
      pregnancy, both normal and abnormal, in animal models and humans. For this study,
      Raman spectra were acquired before, during and after a 19-day mouse gestational
      period. In some cases, after Raman data was obtained, cervices were excised for
      structural testing and histological staining for collagen and smooth muscle.
      Various peaks of the Raman spectra, such as the areas corresponding to fatty acid
      content and collagen organization, changed as the cervix became softer in
      preparation for labor and delivery. These findings correspond to the increase in
      compliance of the tissue and the collagen disorganization visualized with the
      histological staining. The results of this study suggest that non-invasive RS can
      be used to study cervical changes during pregnancy, labor and delivery and can
      possibly predict preterm delivery before overt clinical manifestations,
      potentially lead to more effective preventive and therapeutic interventions.

PMID- 22411266
TI  - The influence of ischemic factors on the migration rates of cell types involved
      in cutaneous and subcutaneous pressure ulcers.
AB  - A pressure ulcer (PU) is a localized injury to the skin and/or to underlying
      tissues, typically over a weight-bearing bony prominence. PUs often develop in
      ischemic tissues. Other than being relevant to the etiology of PUs, ischemic
      factors such as glucose levels, acidity and temperature could potentially affect
      healing processes as well, particularly, the rate of damage repair. Using an in
      vitro cell culture model, the goal of the present study was to determine the
      influence of ischemic factors: low temperature (35  degrees C), low glucose (1
      g/L) and acidic pH (6.7) on the migration rate of NIH3T3 fibroblasts, 3T3L1
      preadipocytes and C2C12 myoblasts, which could all be affected by PUs. Cell
      migration into a local damage site, produced by crushing cells under a micro
      indentor, was monitored over ~16 h under controlled temperature and pH
      conditions. We found that in the NIH3T3 cultures, acidosis significantly hindered
      the migration rate as well as delayed the times for onset and end of mass cell
      migration. The effects of temperature and glucose however were not significant.
      Additionally, under control conditions (temperature 37  degrees C, glucose 4.5
      g/L, pH 7.6), migration rates and times differed significantly across the
      different cell types. The present findings motivate further studies related to
      the effects of pH levels on migration performances, particularly in PU where
      bacterial contamination-associated with an acidic environment-is involved.

PMID- 22411267
TI  - Linear growth and circulating insulin-like growth factor I in children with
      tufting enteropathy receiving long-term TPN.
AB  - We analyzed the growth of 12 children with tufting enteropathy for 2 years
      receiving total parenteral nutrition (TPN). At diagnosis, the length standard
      deviation score (SDS) (-2.15 +/- 1.8) and body mass index (BMI) (12.6 +/- 3.9)
      were significantly decreased. The height SDS and BMI of patients increased
      significantly (-1.39 +/- 1.5 and 16.2 +/- 1.9, respectively) after TPN. Partial
      catch-up growth was achieved in 7 of 12 children during the 2-year period,
      whereas linear growth velocity was maintained in an additional 3 patients.
      Insulin-like growth factor I levels correlated significantly with albumin and
      hemoglobin concentrations (P < 0.001), and increments in insulin-like growth
      factor I concentration after TPN were correlated with the changes in the BMI and
      height SDS (P < 001).

PMID- 22411268
TI  - How often do you fail to take all of your medication?

PMID- 22411270
TI  - Intractable diarrhea and a paravertebral mass.

PMID- 22411269
TI  - Rapid test for fecal calprotectin levels in children with Crohn disease.
AB  - Assessment of fecal calprotectin, a surrogate marker of mucosal inflammation, is
      a promising means to monitor therapeutic response in pediatric inflammatory bowel
      disease, especially if the result is readily available. We tested the performance
      of a novel calprotectin rapid test, Quantum Blue, versus the conventional enzyme
      linked immunosorbent assay in 134 stool samples from 56 pediatric patients with
      Crohn disease. The intraclass correlation coefficient analysis reflected good
      agreement (intraclass correlation coefficient 0.97 [95% confidence interval 0.95
      0.98]) but agreement was better in lower values, where dilutions were not
      required. Using a cutoff of 100 MUg/g for normal values, the percentage agreement
      between the 2 tests was 87%. The optimal cutoff values to guide clinical
      decisions in the therapy of inflammatory bowel disease have yet to be determined.

PMID- 22411271
TI  - Neuromuscular and vascular hamartoma of the small intestine in a child.

PMID- 22411272
TI  - Cellular distribution of cell cycle-related molecules in the renal tubules of
      rats treated with renal carcinogens for 28 days: relationship between cell cycle
      aberration and carcinogenesis.
AB  - Some renal carcinogens can induce karyomegaly, which reflects aberrant cell
      division in the renal tubules, from the early stages of exposure. To clarify the
      cell cycle-related changes during the early stages of renal carcinogenesis, we
      performed immunohistochemical analysis of tubular cells in male F344 rats treated
      with carcinogenic doses of representative renal carcinogens for 28 days. For this
      purpose, the karyomegaly-inducing carcinogens ochratoxin A (OTA), ferric
      nitrilotriacetic acid, and monuron, and the non-karyomegaly-inducing carcinogens
      tris(2-chloroethyl) phosphate and potassium bromate were examined. For
      comparison, a karyomegaly-inducing non-carcinogen, p-nitrobenzoic acid, and a non
      carcinogenic non-karyomegaly-inducing renal toxicant, acetaminophen, were also
      examined. The outer stripe of the outer medulla (OSOM) and the cortex + OSOM were
      subjected to morphometric analysis of immunoreactive proximal tubular cells.
      Renal carcinogens, irrespective of their karyomegaly-inducing potential,
      increased proximal tubular cell proliferation accompanied by an increase in
      topoisomerase IIalpha-immunoreactive cells, suggesting a reflection of cell
      proliferation. Karyomegaly-inducing carcinogens increased nuclear Cdc2-,
      gammaH2AX-, and phosphorylated Chk2-immunoreactive cells in both areas, the
      former two acting in response to DNA damage and the latter one suggestive of
      sustained G2. OTA, an OSOM-targeting carcinogen, could easily be distinguished
      from untreated controls and non-carcinogens by evaluation of molecules responding
      to DNA damage and G2/M transition in the OSOM. Thus, all renal carcinogens
      examined facilitated proximal tubular proliferation by repeated short-term
      treatment. Among these, karyomegaly-inducing carcinogens may cause DNA damage and
      G2 arrest in the target tubular cells.

PMID- 22411273
TI  - Investigations of potential susceptibility toward formaldehyde-induced
      genotoxicity.
AB  - Blood samples were taken from three groups of volunteers (30 male smokers, 30
      female non-smokers, and 30 school children) and tested for ex vivo susceptibility
      toward formaldehyde (FA)-induced genotoxicity. Blood samples were exposed to 150
      MUM FA for 2 h, and the induction of DNA-protein crosslinks (DPX) in leukocytes
      was measured by a modification of the alkaline comet assay (i.e., reduction of
      gamma-irradiation induced DNA migration). Removal of DPX was determined by the
      abolition of FA-induced reduction in DNA migration within 4 h after the end of
      the exposure. Induction and persistence of FA-induced DNA lesions was also
      measured by the sister chromatid exchange (SCE) test with cultured lymphocytes
      after treatment of whole blood cultures with FA (150 MUM). Furthermore, the
      expression (mRNA level) of the GSH-dependent formaldehyde dehydrogenase (FDH,
      identical to alcohol dehydrogenase 5; ADH5) was measured in leukocytes by
      quantitative real-time RT-PCR with TaqMan probes. The subjects were also analyzed
      for the GSTM1 and GSTT1 metabolic gene polymorphisms and a correlation analysis
      with the investigated genetic endpoints for FA-induced genotoxicity was
      performed. The results indicate that there are no biologically relevant
      differences between the three study groups with regard to the various indicators
      of cellular sensitivity toward FA-induced genotoxic effects and the expression of
      FDH. The induced genotoxic effects were not associated with polymorphisms in
      GSTM1 and GSTT1. None of the study groups showed particular mutagen sensitivity
      toward FA-induced genotoxicity. These results suggest that a low scaling factor
      to address possible human inter-individual differences in FA-induced genotoxicity
      could be reasonable.

PMID- 22411274
TI  - Detailing the use of magnetohydrodynamic effects for synchronization of MRI with
      the cardiac cycle: a feasibility study.
AB  - PURPOSE: To investigate the feasibility of using magnetohydrodynamic (MHD)
      effects for synchronization of magnetic resonance imaging (MRI) with the cardiac
      cycle. MATERIALS AND METHODS: The MHD effect was scrutinized using a pulsatile
      flow phantom at B(0) = 7.0 T. MHD effects were examined in vivo in healthy
      volunteers (n = 10) for B(0) ranging from 0.05-7.0 T. Noncontrast-enhanced MR
      angiography (MRA) of the carotids was performed using a gated steady-state free
      precession (SSFP) imaging technique in conjunction with electrocardiogram (ECG)
      and MHD synchronization. RESULTS: The MHD potential correlates with flow
      velocities derived from phase contrast MRI. MHD voltages depend on the
      orientation between B(0) and the flow of a conductive fluid. An increase in the
      interelectrode spacing along the flow increases the MHD potential. In vivo
      measurement of the MHD effect provides peak voltages of 1.5 mV for surface areas
      close to the common carotid artery at B(0) = 7.0 T. Synchronization of MRI with
      the cardiac cycle using MHD triggering is feasible. MHD triggered MRA of the
      carotids at 3.0 T showed an overall image quality and richness of anatomic
      detail, which is comparable to ECG-triggered MRAs. CONCLUSION: This feasibility
      study demonstrates the use of MHD effects for synchronization of MR acquisitions
      with the cardiac cycle.

PMID- 22411275
TI  - Is gluconate a good model for isosaccharinate in uranyl(VI) chemistry? A DFT
      study.
AB  - The geometries, relative energies and spectroscopic properties of a range of
      alpha-isosaccharinate complexes of uranyl(VI) are studied computationally using
      ground state and time-dependent density functional theory. The effect of pH is
      accommodated by varying the number of water and hydroxide ligands accompanying
      isosaccharinate in the equatorial plane of the uranyl unit. For 1 : 1 complexes,
      the calculated uranyl nu(asym) stretching frequency decreases as pH increases, in
      agreement with previous experimental data. Three different isosaccharinate
      chelating modes are studied. Their relative energies are found to be pH
      dependent, although the energetic differences between them are not sufficient to
      exclude the possibility of multiple speciation. At higher pH, the uranyl-ligand
      interactions are dominated more by the equatorial OH(-) than by the organic
      ligands. Calculated electronic excitation energies support experiment in finding
      the lowest energy transitions to be ligand -> metal charge transfer. (13)C NMR
      chemical shifts are calculated for the coordinated isosaccharinate in the high pH
      mimics, and show good agreement with experimental data, supporting the
      experimental conclusion that the five-membered chelate ring is favoured at high
      pH. The effect of increasing the isosaccharinate concentration is modelled by
      calculating 1 : 2 and 1 : 3 uranyl : alpha-isosaccharinate complexes. Comparison
      of the results of the present study with those from our closely related
      investigation of uranyl(VI)-D-gluconate complexes (Dalton Transactions 40 (2011)
      11248) reveals strong similarities in structure, bonding, coordination geometry
      and electronic excitations, but also differences in DeltaG for key ligand
      replacement reactions, suggesting that caution should be exercised when using
      gluconate as a thermodynamic model for isosaccharinate in uranyl(vi) chemistry.

PMID- 22411276
TI  - Vowel category formation in Korean-English bilingual children.
AB  - PURPOSE: A previous investigation (Lee & Iverson, 2012) found that English and
      Korean stop categories were fully distinguished by Korean-English bilingual
      children at 10 years of age but not at 5 years of age. The present study examined
      vowels produced by Korean-English bilingual children of these same ages to
      determine whether and when bilinguals establish distinct vowel categories across
      their 2 languages. METHOD: Both English and Korean vowels produced by 40 Korean
      English bilingual children (5 and 10 years of age) were examined in terms of 1st
      formant frequency (F1) and 2nd formant frequency (F2), vowel duration, and F1 and
      F2 formant trajectories. RESULTS: Formant frequencies of vowels produced by the
      bilingual children were similar to those of monolingual English and Korean
      children. The bilinguals distinguished vowel categories across languages using
      both the assimilation and dissimilation mechanisms as identified by Flege,
      Schirru, and MacKay (2003). CONCLUSIONS: Vowel categories developed earlier than
      stops in bilingual children because vowels were typically acquired earlier than
      consonants. The results of this study suggest that detailed phonetic categories
      do not form across the board and that bilingual children may invoke
      multidimensional representations of phonetic categories.

PMID- 22411277
TI  - The impact of listening condition on background noise acceptance for young adults
      with normal hearing.
AB  - PURPOSE: To evaluate the effect of different speech conditions on background
      noise acceptance. A total of 23 stimulus pairings, differing in primary talker
      gender (female, male, conventional), number of background talkers (1, 4, 12), and
      gender composition of the background noise (female, male, mixed) were used to
      evaluate background noise acceptance. METHOD: A repeated measures research design
      was used. Participants were 15 female and 15 male young adults with normal
      hearing. Background noise acceptance was evaluated with the acceptable noise
      level (ANL). RESULTS: The results revealed main effects of primary talker gender,
      number of background talkers, and listener gender. ANL was lower for conditions
      of a female primary talker and for conditions with multitalker backgrounds. Male
      listeners had significantly lower ANLs than female listeners. An interaction
      occurred between primary talker and background noise composition. For female
      primary talker conditions, the male talker backgrounds produced the lowest ANLs.
      For male primary talker conditions, the lowest ANLs were obtained with the female
      and male background talker conditions. CONCLUSIONS: Background noise acceptance
      depends on the listener and the stimulus condition. Stimulus selection can
      influence the measurement of ANL. The results support the use of the commercially
      available ANL materials.

PMID- 22411278
TI  - The effects of modified melodic intonation therapy on nonfluent aphasia: a pilot
      study.
AB  - OBJECTIVE: Positive results have been reported with melodic intonation therapy
      (MIT) in nonfluent aphasia patients with damage to their left-brain speech
      processes, using the patient's intact ability to sing to promote functional
      language. This pilot study sought to determine the immediate effects of
      introducing modified melodic intonation therapy (MMIT), a modification of MIT, as
      an early intervention in stroke patients presenting with Broca's aphasia. METHOD:
      After a randomized controlled single-blind design, 30 acute stroke survivors with
      nonfluent aphasia were randomly assigned to receive MIT treatment or no
      treatment. A pre/post test, based on the responsive and repetition subsections of
      the Western Aphasia Battery, was developed for this study. RESULTS: After 1
      session, a significant within-subject change was observed for the treatment
      group's adjusted total score ( p = .02), and a significant difference between
      groups was found for adjusted total score ( p = .02) favoring the treatment
      group. The treatment group also showed a significant change in their responsive
      subsection scores ( p = .01) when their pre-tests from Visit 1 to Visit 2 were
      compared, whereas the control group showed no change, suggesting a possible carry
      over effect of MIT treatment. CONCLUSION: This study provides preliminary data
      supporting the possible benefits of utilizing MMIT treatment early in the
      recovery of nonfluent aphasia patients.

PMID- 22411279
TI  - New sentence recognition materials developed using a basic non-native English
      lexicon.
AB  - PURPOSE: The objective of this project was to develop new sentence test materials
      drawing on a basic non-native English lexicon that could be used to test speech
      recognition for various listener populations. These materials have been designed
      to provide a test tool that is less linguistically biased, compared with
      materials that are currently available, for sentence recognition for non-native
      as well as native speakers of English. METHOD: One hundred non-native speakers of
      English were interviewed on a range of 20 conversational topics. Over 26 hr of
      recorded non-native English speech were transcribed. These transcriptions were
      used to create a lexicon of over 4,000 unique words. The words from this lexicon
      were used to create the new materials based on a simple syntactic sentence
      structure frame. RESULTS: Twenty lists of 25 sentences were developed. Each
      sentence has 4 keywords, providing 100 keywords per list. Lists were equated for
      rate of occurrence of keywords in lexicon, high-frequency count (total number of
      affricates and fricatives), number of syllables, and distribution of syntactic
      structure. Listening-in-noise results for native-English-speaking, normal-hearing
      listeners indicated similar performance across lists. CONCLUSION: The Basic
      English Lexicon materials provide a large set of sentences for native and non
      native English speech-recognition testing.

PMID- 22411280
TI  - Word learning by preschoolers with SLI: effect of phonotactic probability and
      object familiarity.
AB  - PURPOSE: In this study, the authors investigated whether previous findings of a
      low phonotactic probability/unfamiliar object word-learning advantage in
      preschoolers could be replicated, whether this advantage would be apparent at
      different "stages" of word learning, and whether findings would differ for
      preschoolers with specific language impairment (SLI) and typical development
      (TD). METHOD: Participants included 114 children: 40 with SLI, 39 with TD matched
      for age and gender, and 35 with TD matched for expressive vocabulary and gender.
      Comprehension and production were assessed during word learning and at post-test
      for words that varied in phonotactic probability and object familiarity. RESULTS:
      Across groups, comprehension performance increased significantly from day 1 to
      day 2 and from day 2 to day 3, but there was no significant word/object type
      effect. Production performance increased significantly from day 1 to day 2, from
      day 2 to day 3, and from day 3 to day 4 for all groups, and there was a clear low
      phonotactic probability/unfamiliar object advantage during word learning but not
      at post-test. CONCLUSION: Results help to establish that preschoolers with TD and
      SLI show a low phonotactic probability/unfamiliar object production advantage
      during word learning that is not restricted to the first few exposures to words,
      but continues over time. This study illustrates how the interaction of
      phonological characteristics in nascent and extant words can affect word
      learning.

PMID- 22411281
TI  - Masked priming effects in aphasia: evidence of altered automatic spreading
      activation.
AB  - PURPOSE: Previous research has suggested that impairments of automatic spreading
      activation may underlie some aphasic language deficits. The current study further
      investigated the status of automatic spreading activation in individuals with
      aphasia as compared with typical adults. METHOD: Participants were 21 individuals
      with aphasia (12 fluent, 9 nonfluent) and 31 typical adults. Reaction time data
      were collected on a lexical decision task with masked repetition primes, assessed
      at 11 different interstimulus intervals (ISIs). Masked primes were used to assess
      automatic spreading activation without the confound of conscious processing. The
      various ISIs were used to assess the time to onset and duration of priming
      effects. RESULTS: The control group showed maximal priming in the 200-ms ISI
      condition, with significant priming at a range of ISIs surrounding that peak.
      Participants with both fluent and nonfluent aphasia showed maximal priming
      effects in the 250-ms ISI condition and primed across a smaller range of ISIs
      than did the control group. CONCLUSIONS: Results suggest that individuals with
      aphasia have slowed automatic spreading activation and impaired maintenance of
      activation over time, regardless of fluency classification. These findings have
      implications for understanding aphasic language impairment and for development of
      aphasia treatments designed to directly address automatic language processes.

PMID- 22411282
TI  - Acoustics of clear speech: effect of instruction.
AB  - PURPOSE: This study investigated how different instructions for eliciting clear
      speech affected selected acoustic measures of speech. METHOD: Twelve speakers
      were audio-recorded reading 18 different sentences from the Assessment of
      Intelligibility of Dysarthric Speech (  Yorkston & Beukelman, 1984). Sentences
      were produced in habitual, clear, hearing impaired, and overenunciate conditions.
      A variety of acoustic measures were obtained. RESULTS: Relative to habitual, the
      clear, hearing impaired, and overenunciate conditions were associated with
      different magnitudes of acoustic change for measures of vowel production, speech
      timing, and vocal intensity. The overenunciate condition tended to yield the
      greatest magnitude of change in vowel spectral measures and speech timing,
      followed by the hearing impaired and clear conditions. SPL tended to be the
      greatest in the hearing impaired condition for half of the speakers studied.
      CONCLUSIONS: Different instructions for eliciting clear speech yielded acoustic
      adjustments of varying magnitude. Results have implications for direct comparison
      of studies using different instructions for eliciting clear speech. Results also
      have implications for optimizing clear speech training programs.

PMID- 22411283
TI  - The effect of technology and testing environment on speech perception using
      telehealth with cochlear implant recipients.
AB  - PURPOSE: In this study, the authors evaluated the effect of remote system and
      acoustic environment on speech perception via telehealth with cochlear implant
      recipients. METHOD: Speech perception was measured in quiet and in noise. Systems
      evaluated were Polycom visual concert (PVC) and a hybrid presentation system
      (HPS). Each system was evaluated in a sound-treated booth and in a quiet office.
      RESULTS: For speech in quiet, there was a significant effect of environment, with
      better performance in the sound-treated booth than in the office; there was no
      effect of system (PVC or HPS). Speech in noise revealed a significant interaction
      between environment and system. Subjects' performance was poorer for PVC in the
      office, whereas performance in the sound-treated booth was not significantly
      different for the two systems. Results from the current study were compared to
      results for the same group of subjects from an earlier study; these results
      suggested that poorer performance at remote sites in the previous study was
      primarily due to environment, not system. CONCLUSIONS: Speech perception was best
      when evaluated in a sound-treated booth. HPS was superior for speech in noise in
      a reverberant environment. Future research should focus on modifications to non
      sound-treated environments for telehealth service delivery in rural areas.

PMID- 22411284
TI  - The consonant-weighted envelope difference index (cEDI): a proposed technique for
      quantifying envelope distortion.
AB  - PURPOSE: The benefits of amplitude compression in hearing aids may be limited by
      distortion resulting from rapid gain adjustment. To evaluate this, it is
      convenient to quantify distortion by using a metric that is sensitive to the
      changes in the processed signal that decrease consonant recognition, such as the
      Envelope Difference Index (EDI; Fortune, Woodruff, & Preves, 1994). However, the
      EDI relies on the entire duration of the signal, including portions irrelevant to
      consonant recognition. METHOD: This note describes a computationally efficient
      method of automatically segmenting speech in time according to the syllable
      structure. Our technique uses the 1st derivative of the envelope as a basis.
      Peaks located in the derivative were used to generate a weighting function for
      the computation of a metric of signal distortion. RESULTS: The weighting function
      significantly improved the variance explained in consonant recognition scores
      over previous methods. However, only 3.2% of the variance was explained in the
      revised model. CONCLUSION: This technique was effective in focusing the analysis
      of distortion on specific segments of the signal. Use of the technique has
      implications for speech analysis. The difference in the amplitude envelope of
      consonants is not a robust model of the effect of hearing aid compression on
      consonant recognition.

PMID- 22411285
TI  - The effect of articulatory adjustment on reducing hypernasality.
AB  - PURPOSE: With the goal of using articulatory adjustments to reduce hypernasality,
      this study utilized an articulatory synthesis model (Childers, 2000) to simulate
      the adjustment of articulatory configurations with an open velopharynx to achieve
      the same acoustic goal as normal speech simulated with a closed velopharynx.
      METHOD: To examine the effect of articulatory adjustment on perceived nasality,
      this study used an articulatory synthesis model (Childers, 2000) to synthesize 18
      oral /i/ vowels, 18 nasal /i/ vowels, and 18 nasal /i/ vowels with computer
      generated articulatory adjustments; these vowels were then presented to 7
      listeners for perceptual ratings of nasality following the direct magnitude
      estimation method. RESULTS: Comparisons of nasality ratings of nasal vowels
      showed a significant reduction of perceived nasality after articulatory
      adjustment. Moreover, the acoustic features associated with nasal resonances were
      attenuated and the oral formant structures changed by nasalization were restored
      after articulatory adjustment, which confirmed findings in   Rong and Kuehn
      (2010). CONCLUSION: Appropriate articulatory adjustments are able to reduce the
      nasality of synthetic nasal /i/ vowels by compensating for the acoustic
      deviations caused by excessive velopharyngeal opening. Such compensatory
      interarticulator coordination may have an application in using articulatory
      adjustments to reduce hypernasality in clinical speech therapies.

PMID- 22411286
TI  - Diffusion tensor quantification and cognitive correlates of the macrostructure
      and microstructure of the corpus callosum in typically developing and dyslexic
      children.
AB  - Noninvasive quantitative MRI methods, such as diffusion tensor imaging (DTI), can
      offer insights into the structure-function relationships in human developmental
      brain disorders. In this article, we quantified the macrostructural and
      microstructural attributes of the corpus callosum (CC) in children with dyslexia
      and in typically developing readers of comparable age and gender. Diffusion
      anisotropy, and mean, radial and axial diffusivities of cross-sectional CC
      subregions were computed using a validated DTI methodology. The normalized
      posterior CC area was enlarged in children with dyslexia relative to that in
      typically developing children. Moreover, the callosal microstructural attributes,
      such as the mean diffusivity of the posterior middle sector of the CC, correlated
      significantly with measures of word reading and reading comprehension. Reading
      group differences in fractional anisotropy, mean diffusivity and radial
      diffusivity were observed in the posterior CC (CC5). This study demonstrates the
      utility of regional DTI measurements of the CC in understanding the neurobiology
      of reading disorders.

PMID- 22411288
TI  - Therapy. Affect and affirmations--a 'basic' approach to promote adherence.
AB  - Efforts to improve health-care quality and efficiency will fail if patients with
      chronic disease do not adhere to medications and healthy lifestyles. A novel,
      psychological approach is to change behavior using 'affect' and 'affirmations'.
      We explore this strategy's potential, when added to the existing arsenal of
      interventions, to improve adherence.

PMID- 22411289
TI  - Antiplatelet therapy: Does CYP2C19 genotype affect clinical outcome?

PMID- 22411290
TI  - Antiplatelet therapy. Intracoronary abciximab during PCI for STEMI.

PMID- 22411291
TI  - Anticoagulation therapy. Dabigatran and risk of myocardial infarction.
AB  - Dabigatran has been associated with an increase in acute coronary events when
      compared with warfarin in several randomized trials, and now in a meta-analysis
      by Uchino and Hernandez. We critically review the evidence for this association
      and consider the implications for patient care.

PMID- 22411292
TI  - Management of hypertension in the elderly.
AB  - Hypertension is the most-prevalent modifiable risk factor for cardiovascular
      morbidity and mortality worldwide. Hypertension is highly prevalent among older
      adults (>=65 years), and aging of the population will substantially increase the
      prevalence of this condition. Age-related endothelial dysfunction and increased
      arterial stiffness contribute to the increased prevalence of hypertension,
      particularly systolic hypertension, among the elderly. The incidence of some
      forms of secondary hypertension also increases with age, mainly owing to the use
      of drugs (especially NSAIDs that have pressor effects) and the presence of
      chronic kidney disease, obstructive sleep apnea, and renal artery stenosis.
      Guidelines differ in thresholds and goals for antihypertensive drug therapy in
      the elderly because of a paucity of high-level evidence from randomized
      controlled trials and inconsistencies in the definition of 'elderly'. Medical
      treatment of hypertension reduces cardiovascular morbidity and mortality in the
      elderly, and all guidelines recommend lifestyle modifications and medical
      treatment for elderly patients whose blood pressure exceeds prescribed thresholds
      and who are at moderate or high cardiovascular disease risk. In the absence of
      comorbidities, which constitute 'compelling indications' for the use of specific
      antihypertensive drugs or drug classes, no clear evidence exists to support
      recommendations for the use of particular antihypertensive-drug classes in older
      adults.

PMID- 22411293
TI  - Validation of an informant-reported web-based data collection to assess dementia
      symptoms.
AB  - BACKGROUND: The Web offers unprecedented access to the experience of people with
      dementia and their care partners, but data gathered online need to be validated
      to be useful. OBJECTIVE: To test the construct validity of an informant Web-based
      data collection to assess dementia symptoms in relation to the 15-point
      Dependence Scale (DS). METHODS: In an online survey posted on the DementiaGuide
      website, care partners of people with dementia built individualized profiles from
      the 60-item SymptomGuide and completed a questionnaire, which included the DS and
      a staging tool. RESULTS: In the 250 profilees (155, 62% women, mean age 77
      years), increasing dependence was associated with a greater chance of
      institutionalization. For example, no one at the lowest levels of dependence (DS
      score < 5, n = 33) was in long-term care, compared with half (13/25) of the
      profilees at the highest levels of dependence (DS score > 12) being in
      institutions (chi(2)(4) = 27.9, P < .001). The Web-based DS was correlated with
      the number of symptoms: higher DS scores were associated with a higher stage of
      dementia (F > 50, P < .001). CONCLUSION: In an online survey, the Web-based DS
      showed good construct validity, potentially demonstrating how the Web can be used
      to learn more about dementia progression and how it relates to symptoms
      experienced by patients across the course of dementing illnesses. Even so,
      caution is needed to assure the validity of data collected online.

PMID- 22411294
TI  - Possible deleterious impact of putative gastrointestinal infections in the time
      period of oocyte recruitment on fertilization after IMSI: two case reports of
      consecutive IVF attempts.

PMID- 22411296
TI  - Beyond borders: comparative quantitative research on partner violence in the
      United States and Mexico.
AB  - We employ two surveys to identify similarities and differences in the risk of
      abuse among poor urban Mexican-origin women in the United States and Mexico.
      While the two surveys reveal basic structural similarity in the predictors of
      partner violence, the rate of violence among Mexican women is far lower than
      among either foreign-born or native-born Mexican origin women in the United
      States. While these differences may reflect reality, we argue that survey data
      must be interpreted cautiously and with an understanding of the cultural,
      economic, and political context in which the information is collected as well as
      methodological differences between the surveys.

PMID- 22411295
TI  - Sperm processing by swim-up and density gradient is effective in elimination of
      sperm with DNA damage.
AB  - PURPOSE: DNA damage may occur during sperm processing, thereby negatively
      influencing fertilizing ability of the sperm. The present study was designed to
      compare the effectiveness of gradient and swim-up, either alone or in
      combination, to eliminate sperm with DNA damage. METHODS: A total of 51 subjects
      visiting the University infertility clinic with normozoospermic parameters,
      oligozoospermia and teratozoospermia were included. Semen characteristics were
      analysed by standard criteria; Terminal deoxy nucelotidyl transferase mediated
      dUTP nick end labeling assay was employed for DNA damage assessment. RESULTS: The
      percentage of TUNEL positive sperm after sperm processing was significantly lower
      in normozoospermic (P < 0.05), oligozoospermic (P < 0.001) and teratozoospermic
      samples (P < 0.01). No difference was observed in the incidence of TUNEL positive
      sperm between the various techniques, suggesting that they are comparable.
      CONCLUSIONS: Sperm preparation has been found to result in enrichment of sperm
      with intact chromatin, which is likely to improve the chances of achieving a
      viable pregnancy.

PMID- 22411297
TI  - Measuring social support in battered women: factor structure of the Interpersonal
      Support Evaluation List (ISEL).
AB  - Social support is related to mental health outcomes among battered women. It is
      unclear, however, whether researchers should measure social support as a
      unidimensional or multidimensional concept. Efforts to identify the latent
      dimensions underlying a common measure of social support, the Interpersonal
      Support Evaluation List (ISEL), have yielded inconsistent results. This study
      used exploratory factor analytic procedures to determine the most appropriate
      factor structure for the ISEL. The ISEL was completed by two samples (one help
      seeking, one non-help seeking) of primarily African American, low-income battered
      women who had experienced intimate partner violence (IPV) within the previous
      year. Results indicated that social support in battered women is best
      conceptualized as unidimensional.

PMID- 22411298
TI  - Women's perceptions of safety and risk following police intervention for intimate
      partner violence.
AB  - Police intervention is a primary response to intimate partner violence (IPV) but
      does not guarantee a victim's future safety. This study sought to identify
      factors associated with IPV survivors' perceptions of safety and risk of
      revictimization following police intervention. One hundred sixty-four women
      completed a questionnaire, and 11 of those women also took part in qualitative
      interviews. The findings revealed that feeling unsafe and perceiving oneself to
      be at risk of future violence is associated with experiencing particular forms of
      IPV, including battering, lethality threats, and sexual violence. Having support
      from others and distance from the partner helps women feel safe.

PMID- 22411299
TI  - Situational ambiguity and gendered patterns of arrest for intimate partner
      violence.
AB  - Using data from the 2005 National Incident-Based Reporting System (NIBRS), this
      analysis focuses on the impacts that domestic violence mandatory arrest policies
      have on arrest outcomes in "situationally ambiguous" cases: cases where both the
      female and male partners have been identified by police as both a victim and an
      offender. Results indicate that although officers arrest male partners more
      frequently than female partners, after controlling for incident and individual
      factors, mandatory arrest policies disproportionately affect women. Furthermore,
      correlates of arrest differ for male-only arrests versus female-only arrests.
      These findings are discussed in the context of changing legal responses to
      domestic violence.

PMID- 22411300
TI  - Back to basics: essential qualities of services for survivors of intimate partner
      violence.
AB  - Survivor voice is essential to effectively implement survivor-focused IPV
      (intimate partner violence) services. In this focus group study, domestic
      violence survivors (n = 30) shared detailed perspectives as service seekers and
      recipients, whereas national hotline advocates (n = 24) explored relationships
      between service providers and survivors based on their interactions with both.
      Four thematic categories related to enhancing IPV services emerged: providing
      empathy, supporting empowerment, individualizing care, and maintaining ethical
      boundaries. Advocates identified additional factors that interfered with quality
      services, including the following: inadequate organizational resources, staff
      burnout, lack of training, and poor integration with other community resources.
      Respectful, empowering relationships are the centerpiece for quality IPV
      services.

PMID- 22411301
TI  - The attenuating effect of empowerment on IPV-related PTSD symptoms in battered
      women living in domestic violence shelters.
AB  - Intimate partner violence (IPV) is associated with significant psychological
      distress, including posttraumatic stress disorder (PTSD). However, factors that
      attenuate the impact of IPV on PTSD remain largely unknown. Using hierarchical
      regression, this investigation explored the impact of resource acquisition and
      empowerment on the relationship between IPV and PTSD. Empowerment demonstrated
      greater relative importance over resource acquisition. Specifically, empowerment
      was found to attenuate the impact of IPV severity on PTSD at low and moderate
      levels of violence. The importance of fostering empowerment and addressing PTSD
      in addition to provision of resources in battered women is discussed.

PMID- 22411302
TI  - Effect of an in-clinic IPV advocate intervention to increase help seeking, reduce
      violence, and improve well-being.
AB  - This quasi-experimental study investigated the efficacy of clinic-based advocacy
      for intimate partner violence (IPV) to increase help seeking, reduce violence,
      and improve women's well-being. Eligible and consenting women attending one of
      six selected clinics in the rural Southern United States were assessed for IPV.
      Consenting women disclosing IPV were offered either an in-clinic advocate
      intervention or usual care, depending on the clinic they attended and were
      followed for up to 24 months. Over follow-up time both IPV scores and depressive
      symptoms trended toward greater decline among women in the advocate intervention
      clinics relative to the usual care (business card referral only).

PMID- 22411303
TI  - Specific inactivation of Twist1 in the mandibular arch neural crest cells affects
      the development of the ramus and reveals interactions with hand2.
AB  - BACKGROUND: The basic helix-loop-helix (bHLH) transcription factor Twist1
      fulfills an essential function in neural crest cell formation, migration, and
      survival and is associated with the craniosynostic Saethre-Chotzen syndrome in
      humans. However, its functions during mandibular development, when it may
      interact with other bHLH transcription factors like Hand2, are unknown because
      mice homozygous for the Twist1 null mutation die in early embryogenesis. To
      determine the role of Twist1 during mandibular development, we used the Hand2-Cre
      transgene to conditionally inactivate the gene in the neural crest cells
      populating the mandibular pharyngeal arch. RESULTS: The mutant mice exhibited a
      spectrum of craniofacial anomalies, including mandibular hypoplasia, altered
      middle ear development, and cleft palate. It appears that Twist1 is essential for
      the survival of the neural crest cells involved in the development of the
      mandibular ramal elements. Twist1 plays a role in molar development and cusp
      formation by participating in the reciprocal signaling needed for the formation
      of the enamel knot. This gene is also needed to control the ossification of the
      mandible, a redundant role shared with Hand2. CONCLUSION: Twist1, along with
      Hand2, is essential for the proximodistal patterning and development of the
      mandible and ossification.

PMID- 22411304
TI  - Correlations between diffusion-weighted imaging and breast cancer biomarkers.
AB  - OBJECTIVE: We evaluated whether the apparent diffusion coefficient (ADC) provided
      by diffusion-weighted imaging (DWI) varies according to biological features in
      breast cancer. METHODS: DWI was performed in 190 patients undergoing dynamic
      contrast-enhanced magnetic resonance imaging (MRI) for local staging. For each of
      the 192 index cancers we studied the correlation between ADC and classical
      histopathological and immunohistochemical breast tumour features (size,
      histological type, grade, oestrogen receptor [ER] and Ki-67 expression, HER2
      status). ADC was compared with immunohistochemical surrogates of the intrinsic
      subtypes (Luminal A; Luminal B; HER2-enriched; triple-negative). Correlations
      were analysed using the Mann-Whitney U and Kruskal-Wallis H tests. RESULTS: A
      weak, statistically significant correlation was observed between ADC values and
      the percentage of ER-positive cells (-0.168, P = 0.020). Median ADC values were
      significantly higher in ER-negative than in ER-positive tumours (1.110 vs 1.050 *
      10(-3) mm(2)/s, P = 0.015). HER2-enriched tumours had the highest median ADC
      value (1.190 * 10(-3) mm(2)/s, range 0.950-2.090). Multiple comparisons showed
      that this value was significantly higher than that of Luminal A (1.025 * 10(-3)
      mm(2)/s [0.700-1.340], P = 0.004) and Luminal B/HER2-negative (1.060 * 10(-3)
      mm(2)/s [0.470-2.420], P = 0.008) tumours. A trend towards statistical
      significance (P = 0.018) was seen with Luminal B/HER2-positive tumours.
      CONCLUSIONS: ADC values vary significantly according to biological tumour
      features, suggesting that cancer heterogeneity influences imaging parameters. KEY
      POINTS: DWI may identify biological heterogeneity of breast neoplasms. * ADC
      values vary significantly according to biological features of breast cancer. *
      Compared with other types, HER2-enriched tumours show highest median ADC value. *
      Knowledge of biological heterogeneity of breast neoplasm may improve imaging
      interpretation.

PMID- 22411305
TI  - Comparison of clinical semi-quantitative assessment of muscle fat infiltration
      with quantitative assessment using chemical shift-based water/fat separation in
      MR studies of the calf of post-menopausal women.
AB  - OBJECTIVE: The goal of this study was to compare the semi-quantitative Goutallier
      classification for fat infiltration with quantitative fat-fraction derived from a
      magnetic resonance imaging (MRI) chemical shift-based water/fat separation
      technique. METHODS: Sixty-two women (age 61 +/- 6 years), 27 of whom had
      diabetes, underwent MRI of the calf using a T1-weighted fast spin-echo sequence
      and a six-echo spoiled gradient-echo sequence at 3 T. Water/fat images and fat
      fraction maps were reconstructed using the IDEAL algorithm with T2* correction
      and a multi-peak model for the fat spectrum. Two radiologists scored fat
      infiltration on the T1-weighted images using the Goutallier classification in six
      muscle compartments. Spearman correlations between the Goutallier grades and the
      fat fraction were calculated; in addition, intra-observer and inter-observer
      agreement were calculated. RESULTS: A significant correlation between the
      clinical grading and the fat fraction values was found for all muscle
      compartments (P < 0.0001, R values ranging from 0.79 to 0.88). Goutallier grades
      0-4 had a fat fraction ranging from 3.5 to 19%. Intra-observer and inter-observer
      agreement values of 0.83 and 0.81 were calculated for the semi-quantitative
      grading. CONCLUSION: Semi-quantitative grading of intramuscular fat and
      quantitative fat fraction were significantly correlated and both techniques had
      excellent reproducibility. However, the clinical grading was found to
      overestimate muscle fat. KEY POINTS: Fat infiltration of muscle commonly occurs
      in many metabolic and neuromuscular diseases. * Image-based semi-quantitative
      classifications for assessing fat infiltration are not well validated. *
      Quantitative MRI techniques provide an accurate assessment of muscle fat.

PMID- 22411306
TI  - Perfusion pattern of musculoskeletal masses using contrast-enhanced ultrasound: a
      helpful tool for characterisation?
AB  - OBJECTIVE: We report 54 patients with histologically evaluated musculoskeletal
      masses who underwent grey-scale and contrast-enhanced ultrasound (CEUS), followed
      by ultrasound-guided biopsy. We hypothesise that the definition of a CEUS-based
      enhancement pattern improves the characterisation of tumour malignancy. METHODS:
      Fifty-four patients with soft-tissue masses were examined according to our
      standardised ultrasound procedure. After CEUS, quantitative and qualitative
      perfusion analyses were performed and each mass was assigned to one of four
      preliminarily defined perfusion patterns (P1-P4). Additionally, mass size and
      localisation were recorded. The sensitivity, specificity, positive predictive
      value (PPV) and negative predictive value (NPV) in the definition of malignancy
      were calculated for relevant combinations of localisation, size and perfusion
      pattern. RESULTS: The single event probability for malignancy was 0% for the P1
      and P4 perfusion patterns, and 60% for P2 and 80% for P3. The best combined
      sensitivity (89%) and specificity (85%) was achieved in a "three-feature
      combination" of size >3.3 cm, mass location below the superficial fascia and
      either P2 or P3 perfusion pattern with a PPV of 86% and NPV of 88%. CONCLUSION:
      The proposed definition of perfusion pattern types with CEUS may serve as a new
      and reliable diagnostic tool for distinguishing malignant soft-tissue masses from
      their benign counterparts. KEY POINTS: * CEUS can assess "tumour perfusion". *
      Four typical perfusion patterns are seen on CEUS of musculoskeletal masses. *
      Knowledge of tumour size, localisation and perfusion pattern can help patient
      management.

PMID- 22411307
TI  - New diffusion metrics for spondylotic myelopathy at an early clinical stage.
AB  - OBJECTIVES: To investigate the use of root mean square displacement (RMSD) and
      mean diffusional kurtosis (DK) metrics of q-space imaging data to estimate spinal
      cord compression in patients with early cervical spondylosis. METHODS: We studied
      50 consecutive patients at our institution (22 male, 28 female; mean age 58
      years; age range 20-86 years) who had clinical signs and symptoms suggestive of
      early clinical stage cervical myelopathy. After conventional magnetic resonance
      (MR) imaging, diffusion tensor and q-space image data were acquired using 3-T MR
      imaging. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), RMSD
      and mean DK values were calculated and compared between compressed and
      uncompressed spinal cords. RESULTS: FA and mean DK values were significantly
      lower and RMSD was significantly higher (P = 0.0060, 0.0020 and 0.0062,
      respectively; Mann-Whitney U test with the Bonferroni correction) in compressed
      spinal cords than in uncompressed cords. ADC was also higher in compressed cords,
      but this difference was not statistically significant. CONCLUSIONS: In the
      evaluation of spinal cord damage in early cervical spondylosis, mean DK and RMSD
      values in the spinal cord may be highly sensitive indicators of microstructural
      change and damage. KEY POINTS: * Absolute surgical indications for cervical
      spondylosis with myelopathy remain to be established. * Diffusion tensor MRI
      shows abnormalities in normal-appearing but compressed spinal cord. * Non
      Gaussian diffusion analysis is highly sensitive in revealing spinal cord damage.

PMID- 22411308
TI  - Multiscale modeling of cellular actin filaments: from atomistic molecular to
      coarse-grained dynamics.
AB  - In this article, we present a computational multiscale model for the
      characterization of subcellular proteins. The model is encoded inside a
      simulation tool that builds coarse-grained (CG) force fields from atomistic
      simulations. Equilibrium molecular dynamics simulations on an all-atom model of
      the actin filament are performed. Then, using the statistical distribution of the
      distances between pairs of selected groups of atoms at the output of the MD
      simulations, the force field is parameterized using the Boltzmann inversion
      approach. This CG force field is further used to characterize the dynamics of the
      protein via Brownian dynamics simulations. This combination of methods into a
      single computational tool flow enables the simulation of actin filaments with
      length up to 400 nm, extending the time and length scales compared to state-of
      the-art approaches. Moreover, the proposed multiscale modeling approach allows to
      investigate the relationship between atomistic structure and changes on the
      overall dynamics and mechanics of the filament and can be easily (i) extended to
      the characterization of other subcellular structures and (ii) used to investigate
      the cellular effects of molecular alterations due to pathological conditions.

PMID- 22411309
TI  - Quantum dots hold promise for early cancer imaging and detection.
AB  - Despite all major breakthroughs in recent years of research concerning the
      complex events that lead to cancer expression and metastasis, we are not yet able
      to effectively treat cancer that has spread to vital organs. The various clinical
      phases originating from cancer diagnosis through treatment and prognosis require
      a comprehensive understanding of these events, to utilise pre-symptomatic,
      minimally invasive and targeted cancer management techniques. Current imaging
      modalities such as ultrasound, computed tomography, magnetic resonance imaging
      and gamma scintigraphy facilitate the pre-operative study of tumours, but they
      have been rendered unable to visualise cancer in early stages, due to their
      intrinsic limitations. The semiconductor nanocrystal quantum dots (QDs) have
      excellent photo-physical properties, and the QDs-based probes have achieved
      encouraging developments in cellular (in vitro) and in vivo molecular imaging.
      However, the same unique physical and chemical properties which renowned QDs
      attractive may be associated with their potentially catastrophic effects on
      living cells and tissues. There are critical issues that need to be further
      examined to properly assess the risks associated with the manufacturing and use
      of QDs in cancer management. In this review, we aim to describe the current
      utilisation of QDs as well as their future prospective to decipher and confront
      cancer.

PMID- 22411310
TI  - Lipid rafts, caveolae and GPI-linked proteins.
AB  - Lipid rafts and caveolae are specialized membrane microdomains enriched in
      sphingolipids and cholesterol. They function in a variety of cellular processes
      including but not limited to endocytosis, transcytosis, signal transduction and
      receptor recycling. Here, we outline the similarities and differences between
      lipid rafts and caveolae as well as discuss important components and functions of
      each.

PMID- 22411311
TI  - Caveolae and the regulation of endocytosis.
AB  - Although clathrin-mediated endocytosis constitutes the main pathway for
      internalization of extracellular ligands and plasma membrane components it has
      generally been accepted that other uptake mechanisms-caveolae-mediated and
      noncaveolar raft-dependent endocytosis-also exist. During the last 20 years many
      papers have been published about caveolar endocytosis. These studies have
      fundamentally changed our view about the endocytotic role of caveolae. Views that
      caveolae are permanently static structures1 have been extensively considered and
      rejected. Although the initial steps leading to the pinching off of caveolae from
      the plasma membrane have been studied in details, there are still contradictory
      data about the intracellular trafficking of caveolae. It is still not entirely
      clear whether caveolar endocytosis represents an uptake pathway with distinct
      cellular compartments to avoid lysosomal degradation or ligands taken up by
      caveolae can also be targeted to late endosomes/lysosomes.In this chapter, we
      summarize the data available about caveolar endocytosis focusing on the
      intracellular route of caveolae and we provide data supporting that caveolar
      endocytosis can join the classical endocytotic pathway.

PMID- 22411312
TI  - Caveolin-1: role in cell signaling.
AB  - Caveolins (Cavs) are integrated plasma membrane proteins that are complex
      signaling regulators with numerous partners and whose activity is highly
      dependent on cellular context. Cavs are both positive and negative regulators of
      cell signaling in and/or out of caveolae, invaginated lipid raft domains whose
      formation is caveolin expression dependent. Caveolins and rafts have been
      implicated in membrane compartmentalization; proteins and lipids accumulate in
      these membrane microdomains where they transmit fast, amplified and specific
      signaling cascades. The concept of plasma membrane organization within functional
      rafts is still in exploration and sometimes questioned. In this chapter, we
      discuss the opposing functions of caveolin in cell signaling regulation focusing
      on the role of caveolin both as a promoter and inhibitor of different signaling
      pathways and on the impact of membrane domain localization on caveolin
      functionality in cell proliferation, survival, apoptosis and migration.

PMID- 22411313
TI  - Regulation of eNOS in caveolae.
AB  - Caveolae are a specialized subset of lipid domains that are prevalent on the
      plasma membrane of endothelial cells. They compartmentalize signal transduction
      molecules which regulate multiple endothelial functions including the production
      of nitric oxide (NO) by the caveolae resident enzyme endothelial NO synthase
      (eNOS). eNOS is one of the three isoforms of the NOS enzyme which generates NO
      upon the conversion of L-arginine to L-citrulline and it is regulated by multiple
      mechanisms. Caveolin negatively impact eNOS activity through direct interaction
      with the enzyme. Circulating factors known to modify cardiovascular disease risk
      also influence the activity of the enzyme. In particular, high density
      lipoprotein cholesterol (HDL) maintains the lipid environment in caveolae,
      thereby promoting the retention and function of eNOS in the domain and it also
      causes direct activation of eNOS via scavenger receptor class B, Type I (SR-BI)
      induced kinase signaling. Estrogen binding to estrogen receptors (ER) in caveolae
      also activates eNOS and this occurs through G protein coupling and kinase
      activation. Discrete domains within SR-BI and ER mediating signal initiation in
      caveolae have been identified. Counteracting the promodulatory actions of HDL and
      estrogen, C-reactive protein (CRP) antagonizes eNOS through FcgammaRIIB, which is
      the sole inhibitory receptor for IgG. Through their actions on eNOS, estrogen and
      CRP also regulate endothelial cell growth and migration. Thus, signaling events
      in caveolae invoked by known circulating cardiovascular disease risk factors have
      major impact on eNOS and endothelial cell phenotypes of importance to
      cardiovascular health and disease.

PMID- 22411315
TI  - Caveolin-1 and breast cancer: a new clinical perspective.
AB  - The current chapter focuses on the role of Caveolin-1 (Cav-1) in cellular growth
      with an emphasis on its implication in breast cancer initiation, progression,
      clinical prognosis and as a potential therapeutic target. The role of Cav-1 as a
      tumor suppressor in breast cancer has emerged in the past few years, with dual
      functions on both cancer epithelium as well as the cancer stroma. Its multiple
      functions as a regulator of estrogen signaling and kinase activity and its newly
      found role as an important factor controlling the dynamic relationship between
      cancer epithelia and stroma position Cav-1 as a new therapeutic target for the
      treatment of breast cancer.

PMID- 22411316
TI  - Caveolin-1 and prostate cancer progression.
AB  - Caveolin-1 was identified in the 1990s as a marker of aggressive prostate cancer.
      The caveolin-1 protein localizes to vesicular structures called caveolae and has
      been shown to bind and regulate many signaling proteins involved in oncogenesis.
      Caveolin-1 also has lipid binding properties and mediates aspects of cholesterol
      and fatty acid metabolism and can elicit biological responses in a paracrine
      manner when secreted. Caveolin-1 is also present in the serum of prostate cancer
      patients and circulating levels correlate with extent of disease. Current
      evidence indicates that increased expression of caveolin-1 in prostate
      adenocarcinoma cells and commensurate downregulation of the protein in prostate
      stroma, mediate progression to the castration-resistant phase of prostate cancer
      through diverse pathways. This chapter summarizes the current state of our
      understanding of the cellular and physiologic mechanisms in which caveolin-1
      participates in the evolution of prostate cancer cell phenotypes.

PMID- 22411314
TI  - Recent developments in the interactions between caveolin and pathogens.
AB  - The role of caveolin and caveolae in the pathogenesis of infection has only
      recently been appreciated. In this chapter, we have highlighted some important
      new data on the role of caveolin in infections due to bacteria, viruses and fungi
      but with particular emphasis on the protozoan parasites Leishmania spp.,
      Trypanosoma cruzi and Toxoplasma gondii. This is a continuing area of research
      and the final chapter has not been written on this topic.

PMID- 22411317
TI  - Caveolins and caveolae, roles in insulin signalling and diabetes.
AB  - Much data in the scientific literature demonstrate a fundamental involvement of
      caveolae in insulin action, although particular aspects remain matters of debate.
      The insulin receptor and part of the downstream signalling mediators are
      localized in or recruited to caveolae. Moreover, as part of the signalling,
      insulin receptors are rapidly endocytosed by caveolae in response to the hormone.
      The insulin regulated glucose transporter GLUT4 appears to localize to caveolae
      after insulin-stimulated translocation to the plasma membrane, while the
      endocytosis of GLUT4 may involve a clathrin-mediated process. Insulin resistance
      due to dysfunction of insulin signalling in target tissues is a primary
      cornerstone of Type 2 diabetes. Lack of caveolae makes animals and human beings
      insulin resistant, but there is presently no evidence that caveolae play a role
      in the pathogenesis of insulin resistance in obesity and Type 2 diabetes.

PMID- 22411318
TI  - Atherosclerosis, caveolae and caveolin-1.
AB  - Atherosclerosis is a disease of the blood vessel characterized by the development
      of an arterial occlusion containing lipid and cellular deposits. Caveolae are 50
      100 nm cell surface plasma membrane invaginations that are believed to play an
      important role in the regulation of cellular signaling and transport of molecules
      among others. These organelles are enriched in sphingolipids and cholesterol and
      are characterized by the presence of the protein caveolin-1. Caveolin-1 and
      caveolae are present in most of the cells involved in the development of
      atherosclerosis. The current literature suggests a rather complex role for
      caveolin-1 in this disease, with evidence of either pro- or anti-atherogenic
      functions depending on the cell type examined. In the present chapter, the
      various roles of caveolae and caveolin-1 in the development of atherosclerosis
      are examined.

PMID- 22411319
TI  - Caveolins and heart diseases.
AB  - Caveolins serve as a platform in plasma membrane associated caveolae to
      orchestrate various signaling molecules to effectively communicate extracellular
      signals into the interior of cell. All three types of caveolin, Cav-1, Cav-2 and
      Cav-3 are expressed throughout the cardiovascular system especially by the major
      cell types involved including endothelial cells, cardiac myocytes, smooth muscle
      cells and fibroblasts. The functional significance of caveolins in the
      cardiovascular system is evidenced by the fact that caveolin loss leads to the
      development of severe cardiac pathology. Caveolin gene mutations are associated
      with altered expression of caveolin protein and inherited arrhythmias. Altered
      levels of caveolins and related downstream signaling molecules in
      cardiomyopathies validate the integral participation of caveolin in normal
      cardiac physiology. This chapter will provide an overview of the role caveolins
      play in cardiovascular disease. Furthering our understanding of the role for
      caveolins in cardiovascular pathophysiology has the potential to lead to the
      manipulation of caveolins as novel therapeutic targets.

PMID- 22411321
TI  - Influence of ischemic core muscle fibers on surface depolarization potentials in
      superfused cardiac tissue preparations: a simulation study.
AB  - Thin-walled cardiac tissue samples superfused with oxygenated solutions are
      widely used in experimental studies. However, due to decreased oxygen supply and
      insufficient wash out of waste products in the inner layers of such preparations,
      electrophysiological functions could be compromised. Although the cascade of
      events triggered by cutting off perfusion is well known, it remains unclear as to
      which degree electrophysiological function in viable surface layers is affected
      by pathological processes occurring in adjacent tissue. Using a 3D numerical
      bidomain model, we aim to quantify the impact of superfusion-induced
      heterogeneities occurring in the depth of the tissue on impulse propagation in
      superficial layers. Simulations demonstrated that both the pattern of activation
      as well as the distribution of extracellular potentials close to the surface
      remain essentially unchanged. This was true also for the electrophysiological
      properties of cells in the surface layer, where most relevant depolarization
      parameters varied by less than 5.5 %. The main observed effect on the surface was
      related to action potential duration that shortened noticeably by 53 % as hypoxia
      deteriorated. Despite the known limitations of such experimental methods, we
      conclude that superfusion is adequate for studying impulse propagation and
      depolarization whereas repolarization studies should consider the influence of
      pathological processes taking place at the core of tissue sample.

PMID- 22411320
TI  - Caveolins and lung function.
AB  - The primary function of the mammalian lung is to facilitate diffusion of oxygen
      to venous blood and to ventilate carbon dioxide produced by catabolic reactions
      within cells. However, it is also responsible for a variety of other important
      functions, including host defense and production of vasoactive agents to regulate
      not only systemic blood pressure, but also water, electrolyte and acid-base
      balance. Caveolin-1 is highly expressed in the majority of cell types in the
      lung, including epithelial, endothelial, smooth muscle, connective tissue cells,
      and alveolar macrophages. Deletion of caveolin-1 in these cells results in major
      functional aberrations, suggesting that caveolin-1 may be crucial to lung
      homeostasis and development. Furthermore, generation of mutant mice that under
      express caveolin-1 results in severe functional distortion with phenotypes
      covering practically the entire spectrum of known lung diseases, including
      pulmonary hypertension, fibrosis, increased endothelial permeability, and immune
      defects. In this Chapter, we outline the current state of knowledge regarding
      caveolin-1-dependent regulation of pulmonary cell functions and discuss recent
      research findings on the role of caveolin-1 in various pulmonary disease states,
      including obstructive and fibrotic pulmonary vascular and inflammatory diseases.

PMID- 22411322
TI  - Embryonic stem cells for severe heart failure: why and how?
AB  - The experience accumulated in cardiac cell therapy suggests that regeneration of
      extensively necrotic myocardial areas is unlikely to be achieved by the sole
      paracrine effects of the grafted cells but rather requires the conversion of
      these cells into cardiomyocytes featuring the capacity to substitute for those
      which have been irreversibly lost. In this setting, the use of human pluripotent
      embryonic stem cells has a strong rationale. The experimental results obtained in
      animal models of myocardial infarction are encouraging. However, the switch to
      clinical applications still requires to address some critical issues, among which
      the optimization of the cardiac specification of the embryonic stem cells, the
      purification of the resulting progenitor cells so as to graft a purified
      population devoid from any contamination by residual pluripotent cells which
      carry the risk of tumorigenesis, and the control of the expected allogeneic
      rejection by clinically acceptable methods. If the solution to these problems is
      a prerequisite, the therapeutic success of this approach will also depend on the
      capacity to efficiently transfer the cells to the target tissue, to keep them
      alive once engrafted, and to allow them to spatially organize in such a way that
      they can contribute to the contractile function of the heart.

PMID- 22411323
TI  - Inter-individual variability in the pre-clinical drug cardiotoxic safety
      assessment--analysis of the age-cardiomyocytes electric capacitance dependence.
AB  - Electrical phenomena located within the plasma membrane of the mammalian cardiac
      cells are connected with the cells' main physiological functions--signals
      processing and contractility. They were extensively studied and described
      mathematically in so-called Hodgkin-Huxley paradigm. One of the physiological
      parameters, namely cell electric capacitance, has not been analyzed in-depth. The
      aim of the study was to validate the mechanistic model describing the capacitive
      properties of cells, based on a collected experimental dataset which describes
      the electric capacitance of human ventricular myocytes. The gathered data was
      further utilized for developing an empirical correlation between a healthy
      individual's age and cardiomyocyte electric capacitance.

PMID- 22411324
TI  - Contained versus uncontained lesions in juvenile elbow osteochondritis dissecans.
AB  - BACKGROUND: Juvenile osteochondritis dissecans (OCD) of the elbow typically
      affects the capitellum and may be "contained" (surrounded by intact cartilage) or
      "uncontained" (extending beyond the lateral cartilaginous margin). The purpose of
      this investigation was to compare the clinical presentation, radiographic
      findings, and surgical results of patients with contained versus uncontained
      lesions. METHODS: Forty-three elbows in 42 patients who underwent surgery for OCD
      were followed for an average of 19.5 months. Average age at surgery was 14.2
      years (range, 11.2 to 18.2 y); there were 16 female and 26 male patients.
      Preoperative magnetic resonance imaging was analyzed for location and size of the
      lesions, alignment and size of the radial head, presence of loose bodies, and
      lesion grades. Patients with contained and uncontained lesions were compared on
      the basis of preoperative characteristics, operative findings, and postoperative
      results. RESULTS: During surgeries of the 43 elbows, 22 elbows had loose bodies,
      which were removed, 32 underwent drilling, and 6 lesions had internal fixation of
      the OCD lesion. Twenty-nine of the 43 elbows (67%) had contained lesions, and 14
      (33%) were uncontained. Preoperatively, uncontained lesions had greater, but not
      statistically significant, flexion contractures (24.8 vs. 14.3 degrees, P=0.088),
      and more swelling (9/14, 64% vs. 7/29, 24%, P=0.007). There was a trend toward
      significance for the uncontained lesions to be larger (155 vs. 125 mm, P=0.15)
      and shallower (7.0 vs. 7.6 mm, P=0.07). Postoperatively, uncontained lesions
      again had greater flexion contracture (13.4 vs. 3.3 degrees, P=0.025).
      CONCLUSIONS: At short-term follow-up, uncontained elbow OCD lesions have greater
      flexion contracture when compared with contained lesions. They also have higher
      rates of joint effusion and are broader and shallower than contained lesions.
      LEVEL OF EVIDENCE: Prognostic level IV.

PMID- 22411325
TI  - Short-term results of arthroscopic treatment of osteochondritis dissecans in
      skeletally immature patients.
AB  - BACKGROUND: Osteochondritis dissecans (OCD) of the capitellum occurs in
      skeletally immature athletes, and most likely results from repetitive trauma
      during overhead activities. Treatment may consist of activity modifications,
      internal fixation, abrasion chondroplasty, microfracture, antegrade drilling,
      retrograde drilling, osteochondral autograft or allograft implantation,
      chondrocyte implantation, and rib autograft through arthroscopy or arthrotomy.
      One treatment modality has not been proven to be clearly more effective than the
      others. This study was undertaken to evaluate our treatment regimen that utilized
      arthroscopic-assisted treatments of capitellar OCD, including removal of loose
      bodies, antegrade or retrograde drilling, and chondroplasty in the pediatric
      population. METHODS: All patients treated arthroscopically for a diagnosis of
      capitellar OCD over a 5-year period, were retrospectively reviewed. All were
      asked to return for follow-up questionnaire and radiographs. Exclusion criteria
      included those lost to follow-up. Demographics were recorded and range of motion
      was evaluated preoperatively and at most recent follow-up for flexion, extension,
      supination, and pronation. Preoperative and the most recent anterior/posterior
      and lateral radiographs of the elbow were reviewed. A 200-point elbow rating
      scale was used to assess patient outcomes. The arthroscopic appearance of the
      lesion was graded. Changes in preoperative to postoperative range of motion and
      size of lesion were compared using repeated measures analysis of variation.
      RESULTS: There were 13 elbows in 12 patients; only 3 of the injuries occurred
      acutely. Mean age at the time of surgery was 13.1+/-1.07 (range, 10.8 to 14.6 y).
      Mean follow-up was 23.4+/-16.7 months (range, 2 to 60 mo). There were 3 grade I
      lesions, 2 grade II lesions, 1 grade IV lesion, and 7 grade V lesions. Seven of
      the lesions underwent transhumeral drilling, 2 transarticular drilling, 3 loose
      body removals, and 2 had only debridement. There were no postoperative infections
      or neurovascular injuries. Three of the elbows (20%) required eventual arthrotomy
      at a mean of 27.9 months after the index procedure. At final follow-up, 67%
      reported no pain and 33% reported occasional pain. No patients reported any
      swelling. Eighty-three percent reported no locking or catching and 17% reported
      occasional locking or catching. No patients reported any activity restrictions.
      The mean subjective score was 96+/-6 of 100 and the mean objective score was 100
      of 100. Mean extension improved significantly from -17 to -7 degrees (P<0.001).
      CONCLUSIONS: Treatment of children with OCD lesions of the capitellum with
      arthroscopic-assisted debridement and fenestration of the sclerotic rim (trans
      humeral if overlaying cartilage is intact), plus fixation of the overlaying
      cartilage if not securely attached to the subchondral bone permits the return to
      physical activity, but may not allow return to the injury-inducing sport. Our
      short-term outcomes obtained using this regimen found this technique to be safe
      and reliable, but other interventions may be required if continued disability
      persists.

PMID- 22411326
TI  - Complications of supracondylar osteotomies for cubitus varus.
AB  - BACKGROUND: Humeral osteotomies for cubitus varus have a notoriously high
      complication rate. Pitfalls of this difficult procedure are highlighted. METHODS:
      A 50-year experience of 68 consecutive surgeries was reviewed. Factors such as
      surgical approach and fixation technique were compared for complication incidence
      and type. RESULTS: Seventeen patients (25%) had 23 (34%) clinically remarkable
      complications. Nine postoperative nerve palsies occurred in 8 patients. Loss of
      reduction requiring revision or manipulation was seen in 3 patients. The
      following complications were noted in 2 patients each: nonunion, loss of flexion,
      lateral prominence, and unsatisfactory scar. Growth arrest, osteomyelitis, and
      under-correction requiring revision each occurred once. A lateral, triceps
      sparing approach was associated with an overall prevalence of complications of
      24% (5 of 21) equivalent to the posterior, triceps splitting approach of 24% (10
      of 42). An olecranon osteotomy was used in 2 patients both with complications. No
      nerve injuries occurred in patients who underwent a lateral approach, whereas
      nerve palsies occurred in 14% (6 of 42) of the patients where a posterior
      approach was used. An olecranon osteotomy was used in 2 patients with nerve
      injury occurring in both. A medial approach in 2 patients and a combined medial
      lateral approach in 1 patient were used with no complications. Plate and screw
      fixation was implemented in 29 cases with complications occurring in 6 of them;
      pin fixation, in 30 cases, 7 of which had complications. There was a higher
      incidence of under-correction requiring additional surgery with plate fixation (1
      of 29) compared with pin fixation which had no under correction but had loss of
      fixation in 2 of 30. The average correction obtained was similar in the group
      with complications (32 degrees) versus those without (27 degrees). CONCLUSIONS:
      Supracondylar humeral osteotomy is a technically demanding procedure fraught with
      complications. Plate fixation and pin fixation techniques resulted in similar
      complication rates, but the surgical approach used appeared to make a difference.
      The posterior, triceps splitting, approach resulted in a high incidence of nerve
      palsies versus none with the lateral, triceps-sparing approach. LEVEL OF
      EVIDENCE: This is a retrospective case series, Level IV.

PMID- 22411327
TI  - The location of medial patellofemoral ligament injury in adolescents and
      children.
AB  - BACKGROUND: The location of medial patellofemoral ligament (MPFL) tears has been
      well documented in the adult population, with most occurring at the insertion of
      the ligament on the adductor tubercle. It is not clear whether a difference
      exists in the pediatric and adolescent populations. The location of the injury
      has implications for treatment recommendations and planning surgical approaches.
      The purpose of this study is to determine whether the location of MPFL injury
      differs among the adult and younger populations. Our hypothesis is that the
      location of MPFL tears in adolescents and children is not predominantly at the
      adductor tubercle. METHOD: At our institution, we retrospectively reviewed 113
      children aged 5 to 17, who were surgically treated for a patellar dislocation.
      All patients had confirmation of a patellar dislocation or severe subluxation.
      Imaging studies, clinic notes, and operative notes were used to determine the
      location of the MPFL injury. RESULTS: Proportion of MPFL injuries found
      intraoperatively at the adductor tubercle was larger than 0.5 (z test=2.97).
      Percentage of MPFL tears at the adductor tubercle was 73% of the cases studied.
      CONCLUSIONS: The location of MPFL injuries found intraoperatively at the adductor
      tubercle was 73% in our series. This is slightly lower than MPFL tear location in
      the adult population, which has been reported to be between 80% and 100%. Our
      hypothesis that the location of MPFL tears in adolescents and children is not
      predominantly at the adductor tubercle was proven false. This study has clinical
      applications for treatment recommendations and planning surgical approaches for
      the pediatric patient with a tear of the MPFL. LEVEL OF EVIDENCE: Level II
      prognostic.

PMID- 22411328
TI  - Access to care for the adolescent anterior cruciate ligament patient with
      Medicaid versus private insurance.
AB  - PURPOSE: To determine the potential impact of type of health insurance on access
      to outpatient orthopaedic care for an adolescent patient with an acute anterior
      cruciate ligament (ACL) tear. METHODS: The offices of 42 orthopaedic surgeons in
      the Greater Cincinnati area, to include Ohio, Indiana, and Kentucky were
      contacted on 2 separate occasions describing a fictitious 14-year-old male with
      an acute ACL tear. The 2 calls were separated by a period of 2 to 4 weeks. The
      independent variable was the patient's insurance status, reported as either
      Medicaid or private insurance. Statistical comparison of the rates of successful
      appointment scheduling was performed through the Fisher exact test. RESULTS:
      Thirty-eight of 42 Orthopaedic surgery practices (90%) offered the privately
      insured 14-year-old ACL patient an appointment within 2 weeks, while only 6 of 42
      (14%) offered the Medicaid patient such an appointment. The difference in these
      rates was statistically significant (P<0.0001) with the odds of getting an
      appointment with private insurance being 57 times higher than that with Medicaid
      (95% confidence interval: 12.87, 288.62). CONCLUSIONS: Access to orthopaedic care
      for children on Medicaid continues to be a problem in the United States. Previous
      pediatric studies have documented that the reason for these discrepancies in
      access are related primarily to Medicaid reimbursement rates (approximately 23%
      of private insurance). Ours is the first study to show that these same
      limitations exist for teenagers with acute knee injuries likely to require
      surgery.

PMID- 22411329
TI  - Measurement of prevertebral cervical soft tissue thickness on lateral digital
      radiographs.
AB  - BACKGROUND: Widening of the prevertebral soft tissues is one of several
      significant indirect signs of cervical spine trauma. This paper provides
      pediatric radiographic reference measurements for prevertebral soft tissues at C2
      and C6, and for the ratio of soft tissue to vertebral width at C6. METHODS: We
      reviewed 327 radiographs of consecutive patients under 14 years of age presenting
      at a trauma unit and obtained the relevant measurements using a software tool.
      Patients included in the study had no clinical features of cervical spine injury.
      Interobserver reliability of the measurements was assessed using the intraclass
      correlation coefficient of reliability. The effect of age category on the
      measurements was tested. RESULTS: Interobserver reliability was high for all
      measurements. The mean soft tissue width at C6 was significantly different across
      3 age categories, whereas there was no significant difference for the soft tissue
      at C2 or the C6 ratio. The highest C2 soft tissue measurement was 10.6 mm,
      whereas the mean was 4.3 mm. The highest ratio at C6 was 1.2, with a mean ratio
      of 0.69. CONCLUSIONS AND CLINICAL RELEVANCE: We present prevertebral soft tissue
      measurements from a larger sample of subjects than published previously, which
      allows our values to be used with more confidence as a tool in screening for
      cervical spine injury.

PMID- 22411330
TI  - Correction of moderate (<70 degrees) Lenke 1A and 2A curve patterns: comparison
      of hybrid and all-pedicle screw systems at 2-year follow-up.
AB  - BACKGROUND: Multiple reports have demonstrated the superiority of all-pedicle
      screw constructs, over hybrid and hook constructs, for severe sagittal and
      coronal deformities (>70 degrees) and have made anterior spinal releasing
      unnecessary for almost all spinal deformities. However, for lesser deformities,
      specifically coronal deformities <70 degrees, published studies have not been
      able to consistently demonstrate clinical superiority of all-pedicle screw
      constructs over hook or hybrid constructs. METHODS: A prospective, multicenter
      database on AIS identified patients with <70 degrees main thoracic (MT) curves
      surgically treated with a posterior spinal fusion. Inclusion criteria were: Lenke
      1A and 2A curve patterns, neurologically normal, primary surgery only, and at
      least 13 years of age at surgery or be Risser 3 or greater and a construct
      consisting of all-pedicle screws (PS) or hybrid instrumentation. Minimum follow
      up was 2 years postoperative. Patients were excluded if surgeries included any
      releases (laminectomies, ligament releases, or osteotomies), which may increase
      curve flexibility. RESULTS: A total of 101 patients satisfied the criteria for
      inclusion: PS (n=53) and hybrid (n=48). Preoperative patient data, preoperative
      curve characteristics, and operative data were similar between the 2 groups.
      Postoperative thoracic coronal Cobb demonstrated PS had better proximal thoracic
      (PT) and MT correction, MT Cobb correction % and correction index than hybrid.
      Interestingly there were no differences in correction index/fixation point
      between the 2 groups, indicating PS constructs achieved better correction due, at
      least in part, to the greater number of spine fixation points. Lower instrumented
      vertebrae tilt and rotational correction was better in the PS group than hybrid.
      At 2-year follow-up PS had better absolute forced expiratory volume in 1 second
      values, trunk shift, and total scoliosis appearance questionnaire than hybrids.
      T5-T12 sagittal alignment was unchanged at 2-year follow-up for PS versus
      increased kyphosis in hybrids. CONCLUSIONS: All-pedicle screw systems had better
      coronal correction, lower instrumented vertebrae tilt, MT scoliometer
      measurements and scoliosis appearance questionnaire total measures than hybrid
      constructs. The improved coronal correction in the PS group is likely due, in
      part, to the higher number of spine fixation points than used in the hybrid
      groups.

PMID- 22411331
TI  - Return to athletic activity after posterior spinal fusion for adolescent
      idiopathic scoliosis:  analysis of independent predictors.
AB  - BACKGROUND: The cause of adolescent idiopathic scoliosis (AIS) is unknown and is
      currently believed to be multifactorial. AIS is a largely asymptomatic condition
      and many adolescents with AIS are involved with organized athletics and physical
      activity. To date, no data exist indicating predictors of return to physical
      activity after posterior spinal fusion for AIS. In this cohort study, adolescents
      who underwent posterior spinal fusion for AIS were evaluated to determine what
      clinical, surgical, and demographic variables predicted rate of return play in
      organized athletics. METHODS: Forty-two athletically active adolescents who
      underwent posterior spinal fusion for AIS at a single tertiary care academic
      orthopaedic institution by a single surgeon were analyzed for clinical, surgical,
      and demographic predictors of return to presurgical activity levels. Data were
      collected by chart review, patient interview, and completion of postoperative SRS
      22 outcomes score. RESULTS: At an average of 5.5 years follow-up, 25 patients
      (59.5%) had returned to sports at an equal or higher level of physical activity.
      Three variables were independently associated with return to athletic activity
      postoperatively. The relationship between distal level of fusion and rate of
      return to play demonstrated a statistically significant stepwise decline from T11
      to L4. Lenke classification and final SRS-22 score were also predictive of return
      to activity. No complications related to return to play were reported.
      CONCLUSIONS: In this retrospective cohort study, distal level of fusion, Lenke
      classification, and postoperative SRS-22 score were each independent predictors
      of rate of return to preoperative level of athletic activity after posterior
      spinal fusion for AIS. LEVEL OF EVIDENCE: Prognostic Level II: retrospective
      Study.

PMID- 22411332
TI  - A multidisciplinary approach improves infection rates in pediatric spine surgery.
AB  - BACKGROUND: Surgical site infections (SSI) associated with elective pediatric
      spinal surgery are a commonly reported complication, increasing hospital length
      of stay, readmissions, operations, and financial costs. In July 2007, a
      multidisciplinary task force, designated Target Zero, was created to address this
      issue and establish prevention protocols at our institution. METHODS: A
      consecutive series of 394 patient charts from April 2006 to September 2008 were
      retrospectively reviewed to identify patients who developed an SSI secondary to
      elective spinal surgery. Four cohorts were evaluated; high-risk (HR) and low-risk
      (LR) patients who underwent surgery before (April 2006 to June 2007) and after
      (July 2007 to September 2008) Target Zero initiation. The definition of HR
      included diagnoses of cerebral palsy, spina bifida, muscle disease, paralytic
      deformities, and vertebral column resections. Patients were followed for 1 year
      to meet The Center for Disease Control-National Health Safety Network's
      definition of an SSI with an implantable device. Overall infection rates were
      determined for each group and compared statistically. RESULTS: A total of 192
      patients (70 HR and 122 LR) underwent surgery before, and 202 patients (92 HR and
      110 LR) underwent surgery after Target Zero initiation. Overall infection rates
      were reduced from 7.8% to 4.5% (P=0.203), 12.9% to 6.5% (P=0.183), and 4.9% to
      2.7% (P=0.505) for all patients, HR patients, and LR patients, respectively. The
      relative risk reduction was 43.0% for all patients, 49.3% for HR patients, and
      44.6% for LR patients. CONCLUSIONS: Although decreases in overall infection rates
      were not statistically significant, the results from Target Zero were shown to be
      clinically meaningful with a relative risk reduction approaching 50% overall and
      in defined subgroups. Based on the number needed to treat analysis, 1 infection
      in every 16 patients within the HR group, and 1 in 30 overall, was prevented up
      to 1 year postoperatively. This study is the first to document the effectiveness
      of a multidisciplinary team implementing protocols for decreasing infection rates
      in pediatric spine surgery.

PMID- 22411333
TI  - Low back pain in a child associated with acute onset cauda equina syndrome:  a
      rare presentation of an aggressive vertebral hemangioma:  a case report.
AB  - BACKGROUND: Back pain prevalence in the pediatric age group is less compared with
      adults. There is a wide range of possible etiologies, and tumors such as primary
      spinal hemangiomas are uncommon. Most are incidental findings and asymptomatic;
      however, painful lesions can be presented in up to 0.9% to 1.2% of cases. These
      lesions can produce neurologic involvement either spinal cord compression or
      cauda equina syndrome as in our case. The aim of this study is to describe a case
      of low back pain in a child due to a vertebral hemangioma complicated with acute
      cauda equina syndrome, and performed a literature review that will help us to
      recognize this aggressive variance making an early treatment feasible. METHODS: A
      13-year-old female, follow-up in an outer health care center due to a L1
      vertebral hemangioma, characterized by 3 years of low back pain without
      neurologic symptoms presented to our emergency department with an acute cauda
      equina syndrome. RESULTS: An outside magnetic resonance imaging showed complete
      obliteration of the spinal canal at the level of the conus medullaris related to
      retropulsion of bone at L1. She underwent 2-stage surgical treatment: complete
      posterior L1 laminectomy and partial T12-L2 laminectomies, with partial L1
      vertebrectomy and posterior fusion with instrumention from T11 to L3. Three weeks
      later, embolization before anterior fusion with inner body cage was performed.
      Forty months after surgery, she is doing well with no neurologic deficits.
      CONCLUSIONS: Even though hemangiomas are not a common cause of back pain, they
      should be taken into account. It is important to recognize the aggressive
      variance so an early treatment could be performed. There is no enough clinical
      data to establish guidelines of management in children, therefore, the treatment
      should be individualized.

PMID- 22411334
TI  - Acetabular retroversion in Down syndrome.
AB  - BACKGROUND: The management of the unstable Down syndrome hip is challenging, and
      there is controversy about the anatomic factors that may contribute to the
      instability. It has been our observation that children with Down syndrome often
      have a deficient posterior acetabular wall. This is different from other
      congenital acetabular dysplasia where the anatomic deficiency is typically
      anterolateral. These observations suggest that the acetabulum in Down syndrome
      hip dysplasia may be relatively retroverted. The purpose of this study was to
      determine the acetabular version in children with Down syndrome and compare this
      with matched controls from both normal and developmental dysplasia of the hip
      (DDH) populations. METHODS: A cohort of Down patients treated surgically for
      acetabular dysplasia and/or hip instability was matched by age, sex, and side to
      a group of normal controls and compared with a cohort of patients who had
      undergone periacetabular osteotomy for DDH. For all patients, preoperative
      computed tomography scans were used to measure acetabular version through the
      joint center. Statistical differences were determined using analysis of variance
      with alpha=0.05. RESULTS: We identified 16 subjects in each cohort. The average
      acetabular version in the normal control group was 13+/-5 degrees and in the DDH
      cohort was 21+/-7 degrees. In contrast, the mean version in the group of patients
      with Down syndrome was 2+/-11 degrees, indicating increased acetabular
      retroversion; this result was significantly different from both the normal group
      (P=0.02) and those with DDH (P<0.001). According to the criteria described by
      Tonnis for computed tomography measured retroversion, 10/16 patients with Down
      syndrome were severely retroverted compared with only 3/16 normal controls and
      1/16 patients with DDH (P=0.002). CONCLUSIONS: Patients with Down syndrome and
      hip instability seem to have more retroverted acetabula than normal controls and
      patients with DDH. In patients with Trisomy 21, axial imaging should be performed
      to evaluate acetabular version when planning the optimal corrective osteotomy for
      instability and/or acetabular deficiency. LEVEL OF EVIDENCE: Level III
      (prognostic, retrospective case-control).

PMID- 22411335
TI  - Predictors for secondary procedures in walking DDH.
AB  - BACKGROUND: Persistent or recurrent hip dysplasia and/or loss of reduction can
      complicate the treatment of developmental dysplasia of the hip (DDH) in walking
      children. In this study, we identify predictors for secondary procedures after
      open reduction of the hip in walking children with DDH. METHODS: We performed a
      retrospective study of walking children with idiopathic DDH treated with open
      reduction of the hip and followed up for >5 years. Perioperative factors were
      analyzed to investigate predictors of reoperation. Factors associated with the
      need for secondary procedures were identified. Acetabular remodeling was analyzed
      with a graphical plot of serial (0, 6 and 12 mo, and yearly) mean acetabular
      index and SD. RESULTS: There were 49 open reductions of the hip in 42 patients
      (34 female, 8 male) at a mean age of 31.3 months (range, 15.3 to 92.6 mo), with a
      mean follow-up of 9.7 years (5 to 16.9 y). Twelve (24%) patients had open
      reduction only, 15 (31%) had concurrent pelvic osteotomy, 4 (8%) had femoral
      osteotomy, and 18 (37%) had both femoral and pelvic osteotomy. Four (8%) patients
      required repeat open reduction at a mean of 5.1 months (range, 4 to 7.5 mo) after
      index surgery. Twenty-four (49%) patients had at least 1 secondary surgery for
      dysplasia at a mean of 3.2 years after index surgery. Six of the 24 (25%) had 2
      and 2/24 (8.3%) had 3 additional operations. Of the 27 patients who did not have
      concurrent femoral osteotomy at index surgery, 19/27 (73%) required a secondary
      procedure; this significantly predicted the need for reoperation (P<0.001). Only
      5/22 patients with femoral osteotomy at index surgery required a secondary
      procedure. Maximum acetabular remodeling was observed in the first 4 years after
      primary reduction, and the mean acetabular index remodeled from 43.9 to 20.3
      degrees during this period. CONCLUSIONS: Forty-nine percent of the patients in
      this cohort required secondary procedures to treat hip dysplasia. Open reduction
      without concurrent femoral osteotomy strongly predicted the need for a secondary
      procedure. Maximum acetabular remodeling was observed in the first 4 years after
      open reduction. LEVEL OF EVIDENCE: Retrospective case series, level IV.

PMID- 22411336
TI  - Prediction of contralateral slipped capital femoral epiphysis using the modified
      Oxford bone age score.
AB  - BACKGROUND: The purpose of the present study was to determine whether the
      modified Oxford bone score can be used as a predictor for the risk of developing
      contralateral slipped capital femoral epiphysis (SCFE) in children who present
      with a unilateral slip. METHODS: We identified 260 patients treated for
      unilateral SCFE between 1980 and 2002 and followed them up to skeletal maturity
      or until development of contralateral slip. Exclusion criteria included patients
      with endocrine or metabolic disorder, Down syndrome, and those with radiographs
      inadequate to determine the modified Oxford bone score. The initial radiographs
      were given a score ranging from 16 to 26. Statistical analysis was used to
      determine whether the modified Oxford bone score was predictive of future
      development of contralateral slip. A linear regression model was used to estimate
      the probability of future development of a contralateral slip as related to the
      modified Oxford bone score. RESULTS: Of the 260 patients, 64 (24%) developed a
      contralateral slip, at an average of 10 months after initial presentation. Race,
      sex, age, and weight at initial presentation were not predictive of the
      development of contralateral slip. The modified Oxford score and a triradiate
      score of 1 were found to be significant (P<0.0001) predictors, with the modified
      Oxford score a better overall predictor. CONCLUSIONS: The modified Oxford bone
      age score is the best predictor of the risk of development of a contralateral
      SCFE in patients presenting with a unilateral slip. Controversy exists regarding
      prophylactic pinning of a normal hip in patients presenting with unilateral SCFE.
      The benefits of prophylactic pinning must outweigh risk. This study provides
      probability data for predicting a contralateral slip based on the modified Oxford
      bone maturity score that can be shared with families and allows physicians to
      decide their threshold for prophylactically pinning the contralateral hip in
      patients presenting with a unilateral slip. LEVEL OF EVIDENCE: Therapeutic level
      IV, Case series.

PMID- 22411337
TI  - Distal femoral osteotomy using the LCP pediatric condylar 90-degree plate in
      patients with neuromuscular disorders.
AB  - BACKGROUND: In patients with cerebral palsy and other neuromuscular disorders,
      correction of a fixed knee flexion deformity is thought to be crucial for the
      improvement of gait. The distal femoral extension osteotomy (DFO) is one method
      to achieve this goal. The standard implant for fixation of the 2 fragments in DFO
      is the conventional AO blade plate. The aim of this study was to report the
      outcome of using the new LCP Pediatric Condylar 90-Degree Plate for DFO. METHODS:
      Thirty-eight patients undergoing 63 DFOs were included. The mean age was 16.3+/
      4.4 years (range, 4 to 27 y) at the time of surgery. Thirty-two patients had a
      diagnosis of cerebral palsy and 6 patients had other neuromuscular disorders
      including myelomeningocoele and arthrogryposis. Thirteen patients had unilateral
      procedures and 25 had bilateral procedures. RESULTS: The mean duration of the
      surgical intervention was 67.9+/-26.5 minutes (range, 30 to 180 min) and the mean
      blood loss was 100.0+/-42.1 mL (range, 50 to 250 mL). In 84% of the cases, large
      fragment (5.0 mm) implants were used. The mean extension correction in 84% of the
      patients (n=53) was 22.8+/-10.3 degrees (range, 5 to 50 degrees). In this series,
      there were 2 complications in 63 osteotomies (3%). Radiologic follow-up of the
      cohort was until the time of plate removal (14.2+/-4.3 mo; range, 6 to 26 mo).
      Three months after the index operation, all osteotomies were radiologically
      consolidated. At this time and at plate removal, there were no malunions or
      nonunions in this cohort. Clinical follow-up of the cohort was performed until
      the end of the study (mean 35.5+/-6.7 mo; range, 22 to 46 mo). At the end of the
      study, 59 plates (94%) had been removed. CONCLUSIONS: The new LCP Pediatric
      Condylar 90-Degree Plate provides stable and safe fixation of distal femoral
      correction osteotomies in patients with neuromuscular disorders. LEVEL OF
      EVIDENCE: Level IV.

PMID- 22411338
TI  - Treatment of talocalcaneal coalitions.
AB  - BACKGROUND: The purpose of this study was to review outcomes of patients treated
      for symptomatic talocalcaneal coalition with resection and interposition of fat
      graft. METHODS: A retrospective review was performed on all patients who
      underwent surgical treatment for symptomatic talocalcaneal coalition over a 13
      year period. Ninety-three feet were treated with excision and fat graft
      interposition by 6 surgeons. All patients underwent a chart review. Patient's
      outcome was assessed at the last follow-up using the American Orthopaedic Foot
      and Ankle Society Hindfoot scale. Postoperative computed tomography scans were
      available for 20 feet. RESULTS: Forty-nine feet had follow-up of at least 12
      months and had a score obtained through the American Orthopaedic Foot and Ankle
      Society Hindfoot scale. At an average of 42.6 months of follow-up, the average
      score obtained was 90/100 (excellent). The postoperative computed tomography
      scans demonstrated 1 recurrence (3%), which was treated with repeat excision. An
      additional patient was reoperated for failure to excise the coalition completely.
      Eleven patients (34%) underwent a subsequent surgery to correct the alignment of
      the foot. To the best of our knowledge, none of the patients excluded because of
      short follow-up had repeat surgery or recurrence. CONCLUSIONS: A symptomatic
      talocalcaneal coalition can be treated with excision and fat graft interposition,
      and achieve good to excellent results in 85% of patients. Patients should be
      counseled that a subset may require further surgery to correct malalignment.
      LEVEL OF EVIDENCE: Level IV-case series.

PMID- 22411339
TI  - Vascularized fibular periosteal graft:  a new technique to enhance bone union in
      children.
AB  - BACKGROUND: The periosteum in children has strong osteogenic power and is quite
      thick, facilitating procurement. However, it has been rarely used as a
      vascularized flap to enhance bone union in this age range. The purpose of this
      study is to assess the effectiveness of a new vascularized periosteal flap
      harvested from the fibula for the enhancement of bone union in the pediatric age.
      METHODS: Thirteen vascularized fibular periosteal grafts were used in 12
      children, mean age 12.6 years. Indications included the prevention of bone
      allograft-host junction nonunion and treatment of recalcitrant bone nonunion. In
      9 instances, the periosteal flap was harvested as a free flap and in 4 as a
      pedicled flap. Serial radiographs and computed tomography scans were used to
      evaluate the progression of callus formation and bone healing. RESULTS: All flaps
      were successful in promoting bone healing and achieving bone union in a mean time
      of 2.8 months for metaphyseal junctions and 7.1 months for diaphyseal ones,
      except for 1 case, which initially failed due to a pedicle torsion. It was then
      resolved with a second vascularized fibular periosteal grafts, with complete
      union after 5 months. CONCLUSIONS: Transfer of a vascularized fibular periosteal
      flap, either pedicled or as a free flap, is an effective treatment to enhance
      bone union in children in biologically unfavorable scenarios. The properties of
      periosteal tissue in the pediatric age are unique and its use in bone union
      enhancement permits new reconstructive strategies in children different from
      those described in adults. LEVEL OF EVIDENCE: IV.

PMID- 22411340
TI  - Treatment of partial growth arrest using an in vitro-generated scaffold-free
      tissue-engineered construct derived from rabbit synovial mesenchymal stem cells.
AB  - BACKGROUND: Injuries to the epiphyseal plate sometimes result in partial growth
      arrest, which can lead to the development of angular deformities and limb length
      discrepancies in growing children. The aim of this study was to develop a new
      treatment for partial growth arrest of the physis. For this purpose, we
      investigated the feasibility of an in vitro-generated scaffold-free tissue
      engineered construct (TEC) derived from synovial mesenchymal stem cells (MSCs) in
      a rabbit growth arrest model. METHODS: An experimental model for growth arrest
      was created by excising the medial half of the proximal growth plate of tibias
      from 6-week-old New Zealand White rabbits. Three experimental groups were set to
      evaluate TEC implantation: group 1, no implantation as controls; group 2,
      implantation of bone wax as additional controls; and group 3, implantation of TEC
      in the lesion. RESULTS: In group 1, all damaged growth plates were arrested and
      angular deformities appeared 4 weeks later. In groups 2 and 3, angular
      deformities were less than in the control group. Histologic images showed bone
      bridges developed at the damaged growth plate in group 1. Regeneration of growth
      plates was recognized in groups 2 and 3. Histologic examination showed greater
      regeneration of the growth plate in group 3 than in group 2. In addition, MSCs in
      the TEC differentiated into proliferative and prehypertrophic chondrocyte-like
      cells. CONCLUSIONS: A scaffold-free 3D TEC made using cultured synovium-derived
      MSCs differentiated into proliferative and prehypertrophic chondrocyte-like
      cells. CLINICAL RELEVANCE: The results of this experimental study suggest that
      scaffold-free 3D TEC made using cultured synovium-derived MSCs can be a new
      approach for the repair of epiphyseal injury. Clinical effectiveness of a
      scaffold-free 3D TEC for growth arrest remains to be determined.

PMID- 22411341
TI  - Incidence of abdominal tumors in syndromic and idiopathic
      hemihypertrophy/isolated hemihyperplasia.
AB  - BACKGROUND: There is a reported increased risk of intra-abdominal tumors in
      children with both syndromic (SH) and isolated idiopathic hemihyperplasia (IH).
      Recommendations for tumor surveillance have been made, although there is no
      consensus for frequency and duration of screening. Our objective was to review
      the incidence of abdominal neoplasms in our pediatric population with SH and IH.
      METHODS: We reviewed the diagnostic criteria, imaging findings, and any
      associated syndrome in all patients diagnosed with hemihypertrophy over a 10-year
      period. RESULTS: One of 10 patients with SH, a child with Beckwith-Wiedemann
      syndrome, developed a hepatoblastoma resulting in a 10% tumor incidence in
      patients with SH. Three of the 250 (1.2%) children with IH developed an abdominal
      neoplasm. One was diagnosed with adrenal carcinoma and the other 2 with Wilms
      tumor. CONCLUSIONS: We found an increased incidence of abdominal tumors in both
      SH and IH, however, our incidence of tumors with IH is lower than earlier
      reported studies. On the basis of this lower 1.2% incidence, the current
      literature on IH and available molecular genetic testing, it is reasonable to
      recommend referral of these patients to a clinical geneticist to identify
      subgroups with a higher risk for tumor development that are more likely to
      benefit from routine imaging surveillance. LEVEL OF EVIDENCE: II-Retrospective
      study.

PMID- 22411342
TI  - Use of the Ponseti method in the Iranian population.
AB  - BACKGROUND: The most common congenital orthopaedic condition requiring treatment
      is clubfoot. The Ponseti method, which has improved the recurrence rate, is at
      present the most attractive method of treatment in the north of America. The
      purpose of this study was to evaluate the outcome of this method in an Iranian
      population and look for characteristics that may affect the treatment process.
      METHODS: A total of 78 patients (129 feet) were treated by precisely adhering to
      the technique originally introduced by Ponseti. Relapse was defined as any return
      of each of 4 clubfoot components according to the Dimeglio-Bensahel system. The
      mean follow-up period was 24.7 months and relapse was analyzed with respect to
      severity of primary disorder, number of casts, compliance with postcorrection
      bracing and stretching exercise, and educational level of parents. RESULTS: At
      the end of the follow-up, 24 (18.6%) clubfeet experienced relapse as defined. The
      mean time to relapse was 13.7 months, 30 feet had brace noncompliance, and
      stretching was not done for 35 feet. Significant association was detected between
      recurrence and severity of clubfoot, number of casts for complete correction, and
      bracing and stretching exercise noncompliance. CONCLUSIONS: The Ponseti method is
      a successful treatment protocol for idiopathic clubfoot. Its success rate will
      increase with use of abduction orthosis after complete correction and also by
      performing regular stretching exercises. LEVEL OF EVIDENCE: Therapeutic level II.

PMID- 22411343
TI  - Breast cancer: Minding your hot flashes.

PMID- 22411344
TI  - Gynecological cancer: Endometriosis link to invasive subtypes.

PMID- 22411345
TI  - Breast cancer: HER2--a good addiction.

PMID- 22411346
TI  - Chemotherapy: Reduced incidence of major bleeds with semuloparin.

PMID- 22411347
TI  - Breast cancer: Neoadjuvant bevacizumab treatment-signal or noise?

PMID- 22411352
TI  - Breast cancer: Resource poor but ingenuity rich.

PMID- 22411353
TI  - Engagement in psychosocial treatment: its relationship to outcome and care
      pathway progress for women in medium-secure settings.
AB  - BACKGROUND: Engaging patients in treatment in secure settings is a major
      challenge. Engagement is associated with a shorter length of stay, whereas
      treatment non-completion is associated with an increased risk of recidivism.
      AIMS: The aims of this study were to assess differences between high and low
      treatment attendees in a women's medium secure unit and to compare progress over
      the course of their stay. METHODS: Sixty consecutive admissions to a women's
      medium secure unit were classified into high and low treatment attendee groups.
      The two groups were compared in terms of risk behaviours and psychometric
      measures of symptomatology, impulsivity and personality. RESULTS: High treatment
      attendees had a shortened length of stay, showed less disturbed behaviour and
      made more progress in terms of a reduction in symptoms overall and traumatic
      stress symptoms specifically. Low treatment attendees were more likely to have a
      diagnosis of schizophrenia/schizotypal illness than personality disorder, less
      likely to be impulsive and more likely to have scores indicative of severe
      disorder on the personality subscales of the Millon Clinical Multiaxial Inventory
      III. CONCLUSION: Attendance at groups in this medium security unit had clear
      advantages for patients and potential cost savings for services and the
      community, but we found a subgroup of women who found it difficult to attend.
      Given the small sample size, we advocate replication, but our findings suggest
      the following: Implications for practice development of motivational
      interventions to help patients make a therapeutic alliance more accurate
      assessment of treatment readiness, to avoid mistimed interventions that are
      counterproductive more effective deployment of milieu therapeutic approaches to
      stabilise behaviour at an early stage of hospitalisation abandonment of a 'one
      size fits all' approach to groups for mixed patient populations. More
      'customised' approaches would allow more appropriate 'pacing' of treatment and
      adaptations of interventions according to need during the treatment course.

PMID- 22411354
TI  - Mental workload as a key factor in clinical decision making.
AB  - The decision making process is central to the practice of a clinician and has
      traditionally been described in terms of the hypothetico-deductive model. More
      recently, models adapted from cognitive psychology, such as the dual process and
      script theories have proved useful in explaining patterns of practice not
      consistent with purely cognitive based practice. The purpose of this paper is to
      introduce the concept of mental workload as a key determinant of the type of
      cognitive processing used by clinicians. Published research appears to be
      consistent with 'schemata' based cognition as the principle mode of working for
      those engaged in complex tasks under time pressure. Although conscious processing
      of factual data is also used, it may be the primary mode of cognition only in
      situations where time pressure is not a factor. Further research on the decision
      making process should be based on outcomes which are not dependant on conscious
      recall of past actions or events and include a measure of mental workload. This
      further appears to support the concept of the patient, within the clinical
      environment, as the most effective learning resource. 

PMID- 22411355
TI  - Use of continuously MR tagged imaging for automated motion assessment in the
      abdomen: a feasibility study.
AB  - PURPOSE: To investigate the feasibility of measuring motion in the abdomen using
      a continuously tagged magnetic resonance imaging sequence. MATERIALS AND METHODS:
      To assess (nonperiodic) motion in the abdomen, a nontriggered, continuously
      tagged transient field echo (TFE) sequence was implemented that acquires one
      complete 3D dataset per prepulse after a fixed delay. In postprocessing, a
      frequency analysis approach was developed for compact reviewing of the data and
      noise suppression. For proof of principle, a simulation was made and one free
      breathing dynamic in vivo scan was acquired in a healthy volunteer. During the
      dynamic scan the volunteer received glucagon intravenously. RESULTS: The
      simulation showed that this frequency analysis enables the extraction of motion
      at low signal-to-noise ratio levels. Motion information was successfully gathered
      from the in vivo scan. The decline in bowel motion caused by the administration
      of glucagon could be quantitatively measured using the continuously tagged
      sequence. CONCLUSION: Continuously tagged imaging in the abdomen for the purpose
      of automated gathering of motion information is feasible and could aid the study
      of bowel motion.

PMID- 22411356
TI  - Galphai2 signaling: friend or foe in cardiac injury and heart failure?
AB  - Receptors coupled to G proteins have many effects on the heart. Enhanced
      signaling by Galpha(s) and Galpha(q) leads to cardiac injury and heart failure,
      while Galpha(i2) signaling in cardiac myocytes can protect against ischemic
      injury and beta-adrenergic-induced heart failure. We asked whether enhanced
      Galpha(i2) signaling in mice could protect against heart failure using a point
      mutation in Galpha(i2) (G184S), which prevents negative regulation by regulators
      of G protein signaling. Contrary to our expectation, it worsened effects of a
      genetic dilated cardiomyopathy (DCM) and catecholamine-induced cardiac injury.
      Galpha (i2) (G184S/+) /DCM double heterozygote mice (TG9(+)Galpha (i2) (G184S/+))
      had substantially decreased survival compared to DCM animals. Furthermore, heart
      weight/body weight ratios (HW/BW) were significantly greater in TG9(+)Galpha (i2)
      (G184S/+) mice as was expression of natriuretic peptide genes. Catecholamine
      injury in Galpha (i2) (G184S/G184S) mutant mice produced markedly increased
      isoproterenol-induced fibrosis and collagen III gene expression vs WT mice.
      Cardiac fibroblasts from Galpha (i2) (G184S/G184S) mice also showed a serum
      dependent increase in proliferation and ERK phosphorylation, which were blocked
      by pertussis toxin and a mitogen-activated protein/extracellular signal-regulated
      kinase kinase inhibitor. Galpha(i2) signaling in cardiac myocytes protects
      against ischemic injury but enhancing Galpha(i2) signaling overall may have
      detrimental effects in heart failure, perhaps through actions on cardiac
      fibroblasts.

PMID- 22411357
TI  - Well characterized antihistamine 4 receptor antibodies contribute to current
      knowledge of the expression and biology of the human and murine histamine 4
      receptor.

PMID- 22411360
TI  - The ALPHA health-related physical fitness test battery for children and
      adolescents.

PMID- 22411358
TI  - Mesotoga prima gen. nov., sp. nov., the first described mesophilic species of the
      Thermotogales.
AB  - A novel mesophilic member of the Thermotogales, strain MesG1.Ag.4.2, was isolated
      from sediments from Baltimore Harbor, MD, USA. The strain grew optimally at 37 
      degrees C with a doubling time of 16.5 h on xylose. Carbohydrates and
      proteinaceous compounds supported growth and pentoses were preferred over
      hexoses. The strain was strictly anaerobic and growth was slightly stimulated by
      thiosulfate, sulfite, and elemental sulfur. The G + C content of its genomic DNA
      was 45.3 mol%. Strain MesG1.Ag.4.2 and Kosmotoga olearia lipids were analyzed.
      Strain MesG1.Ag.4.2 contained no long-chain dicarboxylic acids and its major
      phospholipid was lyso-phosphatidylserine. Long-chain dicarboxylic acids were
      found in K. olearia and its major phospholipid was cardiolipin, a lipid not yet
      reported in Thermotogales species. Phylogenetic analyses of its two 16S rRNA
      genes placed strain MesG1.Ag.4.2 within the bacterial order Thermotogales. Based
      on the phylogenetic analyses and its low optimal growth temperature, it is
      proposed that the strain represents a novel species of a new genus within the
      family Thermotogaceae, order Thermotogales. The name Mesotoga prima gen. nov.,
      sp. nov. is proposed. The type strain of M. prima is MesG1.Ag.4.2 (= DSM 24739 =
      ATCC BAA-2239).

PMID- 22411361
TI  - [Optimization of energy intake in artificial nutrition: second lecture Jesus
      Culebras].
AB  - A primary goal of nutritional support is to provide the energy requirements
      needed to sustain metabolic processes, maintain body temperature and tissue
      repair. The beginnings of artificial nutrition were characterized by high calorie
      nutritional formulae. The assimilation of physiological concepts, accumulating
      research data and clinical experience led to a progressive reduction of this
      intake. During the decade of the 90s of the past century, the concept of
      permissive underfeeding was proposed. Since then, there has been a controversy
      between supporters of an initial reduction of energy intake for the critical
      patient and advocates of a full administration of the estimated calorie needs
      since the very first days of admission to the Intensive Care Unit. This
      controversy has extended into clinical practice guidelines, showing a clear
      disagreement between recent recommendations of ASPEN and ESPEN. In the future we
      will see the publication of new studies that might better define the evidence on
      which to base the recommendations of caloric intake. There is also a clear need
      to deepen the knowledge about the optimal caloric intake in the non-critically
      ill patient requiring artificial nutrition. It is of great importance that these
      new concepts, which will arise undoubtedly, are incorporated quickly in the
      design of nutritional formulas produced by the pharmaceutical industry. Finally,
      it is important to encourage active participation in continuous educational
      activities in the field of Nutrition for achieving a rapid incorporation in daily
      practice of these new concepts of optimal caloric intake.

PMID- 22411362
TI  - [ALPHA-fitness test battery: health-related field-based fitness tests assessment
      in children and adolescents].
AB  - Hereby we summarize the work developed by the ALPHA (Assessing Levels of Physical
      Activity) Study and describe the tests included in the ALPHA health-related
      fitness test battery for children and adolescents. The evidence-based ALPHA
      Fitness test battery include the following tests: 1) the 20 m shuttle run test to
      assess cardiorespiratory fitness; 2) the handgrip strength and 3) standing broad
      jump to assess musculoskeletal fitness, and 4) body mass index, 5) waist
      circumference; and 6) skinfold thickness (triceps and subscapular) to assess body
      composition. Furthermore, we include two versions: 1) the high priority ALPHA
      health-related fitness test battery, which comprises all the evidence-based
      fitness tests except the measurement of the skinfold thickness; and 2) the
      extended ALPHA health-related fitness tests battery for children and adolescents,
      which includes all the evidence-based fitness tests plus the 4 x 10 m shuttle run
      test to assess motor fitness.

PMID- 22411363
TI  - [Ochratoxin A in foods for human consumption: review].
AB  - INTRODUCTION: Ochratoxin A is a neurotoxic, immunosuppressive, genotoxic,
      carcinogenic and teratogenic mycotoxins present in human food, mainly cereals and
      cereals products, alcoholic beverages and mill products (coffee, cocoa). The
      levels of Ochratoxin A in food are closely related with the production and
      conservation conditions. OBJECTIVE: This review aims to assess the presence of
      OTA in different food groups, and to update the knowledge about its toxicity,
      mechanism of action, methods of analysis used for detection and quantification,
      and different aspects about regulations. METHODS: References and publications
      related to the mechanism of action, toxicity, analysis and regulations about OTA
      in foods were searched and selected based on inclusion criteria. MEDLINE/PubMed,
      Scielo, Science Direct, Ebscohost were used as databases. RESULTS: The presence
      of OTA keeps on being observed in different food groups. The detected OTA levels
      are below those permitted by limits set by the regulations However, inadequate
      agrotechnological production practices and improper storage of foods remain as
      critical control points to avoid the toxic hazards resulting from human exposure
      to this toxin. CONCLUSIONS: It's recommended to promote the correct use of
      agrotechnological practices for raw materials and processed products to reduce
      the concentration of OTA in foods and to avoid the toxicity resulting from the
      consumption of OTA contaminated foods.

PMID- 22411364
TI  - Preoperative weight loss in patients with indication of bariatric surgery: which
      is the best method?
AB  - BACKGROUND: Surgery is the only effective treatment for people with a body mass
      index (BMI) greater than 40 Kg/m2 or even greater than 35 Kg/m2 when some
      diseases like diabetes or hypertension appear. In order to minimize surgical risk
      and improve postoperative results, preoperative preparation it's very important.
      "Acute" preoperative weight loss just before surgery plays a crucial role in that
      preparation and can be achieved through different ways like a low calorie diet, a
      very low calorie diet or with the use of an intragastric balloon. The advantages
      or particularities of every one of them will be summarized in this article.
      MATERIAL AND METHODS: Literature review of the benefits, risks and complications
      of preoperative weight loss through a low calorie diet, a very low calorie diet
      or intragastric balloon placement. RESULTS: Seven of thirteen initially selected
      reports from Medline search were considered relevant, including a total 371
      patients (240 patients treated with low calorie diet, 90 with very low calorie
      diet and 41 cases of intragastric balloon placement). We found that weight loss
      was greater in patients with very low calorie diets and intragastric balloon
      groups but with a slightly increase in morbidity and cost. CONCLUSION: Although
      there are no comparative studies, data from the literature results show that
      diets very low in calories are more effective and require less time than low
      calorie diets and cheaper with fewer side effects than the intragastric balloon.

PMID- 22411365
TI  - [Ethical questions related to nutrition and hidration: basic aspects].
AB  - Conditions that pose ethical problems related to nutrition and hydration are very
      common nowdays, particularly within Hospitals among terminally ill patients and
      other patients who require nutrition and hydration. In this article we intend to
      analyze some circumstances, according to widely accepted ethical values, in order
      to outline a clear action model to help clinicians in making such difficult
      decisions. The problematic situations analyzed include: should hydration and
      nutrition be considered basic care or therapeutic measures?, and the ethical
      aspects of enteral versus parenteral nutrition.

PMID- 22411366
TI  - [Meta-analysis on the role of lycopene in type 2 diabetes mellitus].
AB  - INTRODUCTION: lycopene is a carotene with a potent antioxidant effect found in
      tomato and its derivatives. Given that diabetic patients present an increased
      oxidative stress, lycopene could be beneficial. The aim of this scientific review
      has been to analyze the scientific evidence of the role of lycopene as an anti
      oxidant agent in diabetes, its prevention and the metabolic control and
      development of complications. MATERIALS AND METHODS: We carried out a systematic
      review and meta-analysis. A literature search was done in Medline and the
      Cochrane Library, using the MeSH terms "carotenoids" OR "lycopene" AND "type 2
      diabetes mellitus". The search was manually completed from the references of the
      papers found. The quality of the studies was assessed by using the JADAD and
      STROBE scales. We included a total of 10 articles. RESULTS: After adjusting for
      other risk factors, the OR for developing DM2 as similar among the different
      levels of lycopene intake. The plasma levels of lycopene increase in the
      intervention groups. Lycopene decreases the malonyldialdehyde and lipid
      peroxidation. The non-provitamin A/provitamin A carotenoids ratio is negatively
      associated with the risk for suffering from diabetic retinopathy. CONCLUSION:
      Tomato or lycopene intake increases the plasma levels of this compound. However,
      there is no evidence for the association between lycopene intake and the risk for
      having diabetes. This compound and other tomato derivatives may have a beneficial
      effect on the oxidative stress in diabetic patients. The non-provitamin
      A/provitamin A carotenoids ratio is negatively associated with the risk for
      suffering from diabetic retinopathy, although there are no data available on the
      relationship between lycopene and other diabetic complications.

PMID- 22411367
TI  - Effect of weight loss on metabolic control in people with type 2 diabetes
      mellitus: systematic review.
AB  - OBJECTIVE: The aim of this systematic review was to examine randomized clinical
      trials (RCT) regarding long-term effects of weight loss (WL) on biological
      markers in people with type 2 diabetes mellitus (T2DM). METHODS: We searched for
      articles published in English and Spanish recorded in the databases of Pubmed and
      Cochrane , and the journal collections platforms of Ebsco and Scielo between
      January 1, 2000 and January 1, 2010. Inclusion criteria included RCT with follow
      up >= 12 months. RESULTS: A total of 842 articles were identified, 95 of them
      contained information on the effect of WL on biological markers. Twenty studies
      fulfilled the inclusion criteria. WL percentage ranged from 0.8 to 20%. A
      reduction of A1C was observed in nine studies, blood glucose in seven, of total
      cholesterol and LDL in four, systolic and diastolic blood pressure in three, and
      the use of hypoglycemic drugs in four; an increase of HDL was observed in seven
      studies. Remission of T2DM was reported in only one study, which included
      surgical treatment. The quality of the studies ranged from very low to high;
      however, the study with the longest follow-up that did not involve surgical
      treatment, was 52 months. CONCLUSION: The evidence of the beneficial effect of WL
      on biological markers on long-term studies in people with T2DM is inconclusive.
      These results warrant longer and better designed studies.

PMID- 22411368
TI  - [Effect of food television advertising on the preference and food consumption:
      systematic review].
AB  - OBJECTIVE: The aim of this study was to perform a systematic review of papers
      that assess the effect of television food advertisings (TFA) in the food
      preferences and consumption in different age groups. METHODS: Randomized clinical
      trials published up to November 2010 were searched in Pubmed, Ebsco, Cochrane and
      Scielo. Studies were included if they assessed the effect of direct exposition to
      TFA over the food preferences, demand, and consumption. RESULTS: Ten studies
      fulfilled the inclusion criteria. In the three studies conducted on preschooler
      children an increase in selection and demand of advertized foods was reported.
      All the fives studies conducted on scholar children reported negative outcomes in
      those children exposed to unhealthy food. An increase on food consumption was
      observed in two of the three studies conducted on adults. CONCLUSION: The assess
      studies show that in pre-school and school children the effect of advertising on
      food consumption was consistent, while in adults there is a trend toward an
      strong association of exposure food advertising and preference, consumption and
      demand of the food advertised.

PMID- 22411369
TI  - Long-term efficacy of high-protein diets: a systematic review.
AB  - The rationale for the use of high-protein diets is that they offer a higher level
      of satiety for a longer period of time when compared with carbohydrates or fats;
      this diminishes calorie consumption in the long-run. The purpose of this review
      was to assess the efficacy of long-term randomized clinical trials. We used
      Pubmed, EBSCO and SCIELO to conduct our searches. Inclusion criteria were:
      randomized clinical trials conducted in adults, with an intervention/follow-up of
      at least 24 weeks, stating the specific amount of energy protein (in percentages)
      in the diet; with a control group with either a conventional energy restricted
      diet or a high-fat/high-carbohydrate diet, also the studies should provide at
      least body weight or body mass index (BMI) at the beginning and at the end of the
      intervention. A total of 481 studies were found. Eight studies met the inclusion
      criteria. Weight loss difference in those with the highest weight loss with the
      high-protein diet ranged from 3.7 kg in a six month trial to 1.2 kg in a 17 month
      trial. The average weight loss of the eight studies in the high-protein diet was
      6.3 kg and in the standard diet was 5.0 kg. Although half of the studies showed a
      higher weight loss with a high-protein diet, three out of four studies with the
      longest intervention show no statistical difference in weight loss. In this
      systematic review it was observed that the long-term effect of high-protein diets
      is neither consistent nor conclusive.

PMID- 22411371
TI  - Effect of maternal obesity on lactation: systematic review.
AB  - OBJECTIVE: The short duration or lack of breastfeeding has been associated with
      maternal obesity. The purpose of this study was to systematically review
      prospective studies that assessed the effect of maternal obesity on lactation.
      METHODS: A search of studies was conducted in Pubmed, these included prospective
      studies on maternal obesity and initiation, intention and duration of
      breastfeeding: 653 articles were found, only seven were prospective studies.
      After adding other studies found by hand, a total of nine studies were analyzed.
      RESULTS: Three out of four papers observed a higher risk for delay lactogenesis
      among obese mothers, odds ratio ranging from 1.02 to 1.10. The study assessing
      the initiation of lactation showed that non-obese mothers initiated lactation
      sooner, OR: 0.39 (95% CI: 0.25-0.62). The overall risk for cessation of
      breastfeeding showed that obese mothers had higher risks of early cessation, HR:
      1.50 (CI 95% 1.11-2.04). In one study it was observed that obese mothers were not
      more likely to never breastfeed, OR = 1.56 (95% CI: 0.97-1.50). CONCLUSIONS: This
      review shows that in prospective studies, obese mothers are more likely to have
      delayed lactogenesis and reduced lactation. Therefore, weight control and
      breastfeeding promotion should be reinforced before and during pregnancy. In
      overweight and obese mothers, breastfeeding should be closely monitored after
      birth.

PMID- 22411370
TI  - [Meal replacement efficacy on long-term weight loss: a systematic review].
AB  - Meal replacement (MR) has been frequently used to substitute one or more meals
      during the day. However, few randomized long-term studies have assessed its
      efficacy. OBJECTIVE: To asses meal replacement use and its effectiveness on long
      term weight loss (> 1 year) in overweight and obese people with or without
      diabetes. METHODS: A search of randomized clinical trials with an intervention
      period equal to or more than a year, published on Pubmed, EBSCO host and SciELO
      through November 2010 was performed. Mesh terms such as "meal replacement",
      "weight loss," "overweight," "obesity" and "diabetes" were used, plus the term
      "meal replacement." GRADE scale was used to assess the quality of the studies.
      RESULTS: Seven studies met the inclusion criteria and were analyzed. It was
      observed that four of the studies showed a major weight loss in meal replacement
      groups, but in the other four studies no significant difference in weight loss
      was found. CONCLUSION: The evidence of the beneficial effect of meal replacement
      on long-term weight loss is inconclusive. These results warrant longer and better
      design studies.

PMID- 22411372
TI  - Effects of low carbohydrate diets on weight and glycemic control among type 2
      diabetes individuals: a systemic review of RCT greater than 12 weeks.
AB  - INTRODUCTION: Low carbohydrate diets (LCD) have shown beneficial effects on short
      term weight reduction programs for obese individuals without diabetes, but the
      long-term evidence of efficacy on individuals with type 2 diabetes is not
      conclusive. OBJECTIVE: To evaluate, the effectiveness of 12 or more weeks of LCD
      compared to Low Fat Diet (LFD), Usual Care Diet (UCD) or Low Glycemic Index Diet
      (LGID) on weight reduction and AIC on type 2 diabetes individuals. METHODS: A
      systematic review was conducted on randomized trials registered in PubMed,
      Cochrane and EBSCOhost from January 1st 2000 to January 1st 2010 including those
      with an intervention program with LCD in type 2 diabetes subjects and a follow-up
      >= 12 weeks. Available data on study design; carbohydrate composition of diet;
      duration of diet; and the outcomes of weight, lipid levels (total, low density
      lipoprotein and high-density lipoprotein cholesterol, and triglycerides),
      hemoglobin A1C percent and/or fasting glucose were extracted. RESULTS: Five
      studies showed greater weight reduction with LCD, of which four demonstrated no
      significant difference. The longest trial intervention studies did not show a
      difference in weight change. Only two studies showed greater reduction of A1C
      with LCD, including the longest intervention trial with a low carbohydrate
      Mediterranean diet. CONCLUSIONS: This review shows that there are no consistent
      differences in weight and A1C changes over the long-term treatment with LCD and
      LFD, UCD or LGID.

PMID- 22411373
TI  - [Home parenteral nutrition registry in Spain for the year 2010: NADYA-SENPE
      Group].
AB  - OBJECTIVES: To report the Group Registry NADYASENPE data about home parenteral
      nutrition (HPN) in Spain in 2010. MATERIAL AND METHODS: A descriptive study of
      the database of the national registry of HPN of NADYA-SENPE (December 10, 2009 to
      December 10, 2010). For the calculation of prevalence the latest data published
      by the Institute National Statistics Office (01/01/2009) was used. RESULTS: There
      were registered 148 patients from 23 hospitals, 86 women (58.11%) and 9 children
      (6.08%). The average age of the 139 patients older than 14 years was 53.06 +/-
      15.41 years. The average duration of HPN was 316.97 days/patient. The most common
      diagnosis in those younger than 14 years was short bowel traumatic with 5 cases
      (55.55%) and in those older than 14 years, palliative care cancer with 29 cases
      (19.59%). The reason for the indication for HPN was short bowel syndrome in 74
      cases (47%). The access via most frequently recorded was tunneled catheter in 36
      cases (22.78%) followed by implanted port-catheters in 13 cases (8.23%) and other
      pathways in 3 cases (1.90%). There were 23 catheterrelated infections (82.14%)
      which represented 0.49 /1,000 days of PN, all of which occurred in cases older
      than 14 years. During the year 24 episodes of HPN ended, the most frequent cause
      was the transition to oral nutrition in 12 episodes (50%). It was reported that
      patients had a normal activity in 70 episodes of HPN (44.30%) with complete
      autonomy in 88 episodes (55.69%). Some patients 39 (24.68%) were potential
      candidates for intestinal transplantation. CONCLUSIONS: The number of registered
      patients is slightly lower than the previous year, although the number of
      participating hospitals is the same. The most frequent complication remains
      catheter-related infection but its incidence has decreased from previous years,
      presenting the lowest rate since the creation of the record. Differences in
      participation in the registry observed in the Autonomous Communities causes the
      development of implementation strategies. There is a gradual increase in day
      length of HPN over the years, which suggests the chronic treatments of some
      patients and obliges to study the existence of a possible confounding factor, in
      case there is an oversight of closing an episode. Therefore, it is necessary to
      update the registry with warning systems that facilitate periodic review of the
      patients and optimize the validity of registration.

PMID- 22411374
TI  - Diet creates metabolic niches in the "immature gut" that shape microbial
      communities.
AB  - Although diet composition has been implicated as a major factor in the etiology
      of various gastrointestinal diseases, conclusive evidence remains elusive. This
      is particularly true in diseases such as necrotizing enterocolitis where breast
      milk as opposed to commercial formula appears to confer a "protective effect" to
      the "immature gut." Yet the mechanism by which this occurs continues to remain
      speculative. In the present study we hypothesize that the basic chemical
      composition of diet fundamentally selects for specific intestinal microbiota
      which may help explain disparate disease outcome and therapeutic direction.
      Complimentary animal and human studies were conducted on young piglets (21 d.)(n
      = 8) (IACUC protocols 08070 and 08015) and premature infants (adjusted
      gestational age 34-36 weeks) (n = 11) (IRB Protocol 15895A). In each study, cecal
      or stool contents from two groups (Breast milk-fed (BF) vs. Formula-fed (FF))
      were analyzed by gas chromatography/mass spectrometry (GC/MS) and comprehensive
      metabolic profiles generated and compared. Concurrently, bacterial community
      structure was assayed and respective representative microbiota of the groups
      determined by 16S rRNA gene amplicon pyrosequencing. Statistical modeling and
      analysis was done using SIMCA-P+ and R software. GC/MS metabolomics identified
      clear differences between BF and FF groups in the intestinal environment of
      piglets and humans. Sugars, amino-sugars, fatty acids, especially unsaturated
      fatty acids, and sterols were identified as being among the most important
      metabolites for distinguishing between BF and FF groups. Joint analysis of
      microbiota and metabolomics pinpointed specific sets of metabolites (p < 0.05)
      associated with the dominant bacterial taxa. The chemical composition of diet
      appears to have a significant role in defining the microbiota of the immature
      gut. Tandem analysis of intestinal microbial and metabolic profiles is
      potentially a powerful tool leading to better understanding of the role of diet
      in disease perhaps even leading to specific strategies to alter microbial
      behavior to improve clinical outcome.

PMID- 22411375
TI  - Animal model of undernutrition for the evaluation of drug pharmacokinetics.
AB  - BACKGROUND: Protein energy malnutrition is a public health problem affecting a
      great number of people. Pathophysiological imbalances in malnourished individuals
      have a profound impact on drug pharmacokinetics. OBJECTIVE: To develop an animal
      model of undernutrition using male Wistar rats to be used to assess, in further
      studies, the impact of nutritional status on the oral bioavailability and
      pharmacokinetics of drugs. DESIGN: [corrected] Animals were randomly assigned to
      one of two groups and fed different diets for 26 days: WN (well-nourished/regular
      diet, N = 61) and UN (under-nourished/protein-calorie restricted diet, N = 72).
      Assessment of the animals' nutritional status was performed taking into account
      serum albumin, total cholesterol level and total body weight. A kinetic model
      incorporating population kinetic analysis (NONMEM) was developed to analyze body
      weight versus time profiles in the adaptation period following administration of
      the two aforementioned diets. RESULTS: Serum albumin plasma levels were lower
      than 2.3 g/dL in 80% (60/72) of malnourished animals at the end of the adaptation
      period. The range of the total serum cholesterol was similar in both groups at
      the end of the adaptation period. Total body weight in all cases was less than
      230 g for malnourished animals and higher than 240 g for well-nourished animals.
      The kinetic model assayed was confirmed to be an expansion module characterized
      by linear weight gain and a decline module characterized by exponential weight
      loss, where the weight loss rate constant is an exponential function of time. The
      bootstrap resampling method confirmed the stability of the model eventually
      selected. CONCLUSIONS: The animal model developed in this study is reliable and
      could be of use in evaluating the impact of nutritional state on the
      pharmacokinetics of drugs. The proposed mathematical model allows the body weight
      of animals to be predicted at a given time taking into account the diet followed
      in the experimental period.

PMID- 22411376
TI  - Effectiveness of perioperative glutamine in parenteral nutrition in patients at
      risk of moderate to severe malnutrition.
AB  - BACKGROUND & AIMS: To determine whether perioperative glutamine supplementation
      of parenteral nutrition (PN) has an impact on morbidity and mortality of patients
      with previous moderate to severe risk of malnutrition. METHODS: A quasi
      experimental study was conducted comparing the following groups: Control group 1:
      without glutamine dipeptide supplementation of PN during the perioperative
      period. Control group 2: PN was supplemented with glutamine dipeptide (0.4
      g/kg/day) after surgery only. Group 3 (follow-up group): PN was supplemented with
      glutamine dipeptide (0.4 g/kg/day) in the perioperative period. Postoperative
      morbidity and mortality was recorded. RESULTS: Sixty-seven patients matched for
      baseline and surgical characteristics were recruited into the study. Univariate
      analysis showed a lower incidence of hyperglycemia and ICU admission in group 3,
      and a trend to significance (P = 0.078) in terms of a lower incidence of
      infection. In the multivariate analysis, only group 3 met the models of ICU
      admission (OR = 0.28), hyperglycemia (OR = 0.11), and renal failure (OR = 0.19).
      CONCLUSIONS: The results show that perioperative use of glutamine dipeptide in
      patients at risk of moderate to severe malnutrition before surgery is an
      effective option for decreasing the morbidity associated with malnutrition, as it
      improves blood glucose modulation and reduces infection and ICU stay.

PMID- 22411377
TI  - What motivates the consumer's food choice?
AB  - OBJECTIVE: The aim of the study was to analyse the psychometric properties of the
      Food Choice Questionnaire (FCQ) in Spanish population (FCQ-SP), its factor
      structure and internal consistency. In addition, the relationships between the
      FCQ-SP and the General Health Questionnaire (GHQ), the Irrational Food Beliefs
      Scale (IFBS), and the Eating Disorders Inventory-3 (EDI-3) were analysed in order
      to explore the validity of the FCQSP. Possible gender differences in the food
      choice pattern were analysed. METHODS: The sample comprised 255 women and 50 men,
      ranged from 25 to 64 years. In order to get a better interpretation of the
      results associated with changes based on the age, the participants were grouped
      in four age intervals (25-34, 35-44, 45-54, and 55-64). All the participants were
      relatives of secondary and high school students in three schools of Seville and
      Cordoba. RESULTS: The factor analysis yields the seven following factors: mood,
      health and natural content, sensory appeal, weight control, convenience,
      familiarity, and price. The internal consistency was determined by means of the
      Cronbach's alpha coefficients, which ranged from 0.70 to 0.83 for the different
      components. With regards to the food choice profile, sensory appeal was the most
      motivating factor to choose food, followed by price and weight control. With
      respect to gender differences, women showed higher scores than men in all
      components except in the case of price. DISCUSSION: The FCQ-SP has adequate
      psychometric properties to be applied to Spanish population, and it is useful to
      explore the consumers' motivation with regards to food choice.

PMID- 22411378
TI  - Association of nutritional status, plasma, albumin levels and pulmonary function
      in cystic fibrosis.
AB  - BACKGROUND & AIMS: Malnutrition is related with pulmonary disease. The aim was to
      analyze the association of lung function respectively to nutritional status,
      identified pulmonary pathogens and socioeconomic condition of patients attending
      a pediatric CF reference center. METHODS: Cross-sectional study performed with CF
      patients aged 6 to 18 years attending a CF-Center in southern Brazil. Nutritional
      status, plasma albumin level and pulmonary bacterial colonization were assessed.
      The outcome studied was forced expiratory volume in 1 second (FEV1). RESULTS:
      Eighty-five patients were included in this study. FEV1 was significantly
      associated with body mass index (BMI) percentiles, plasma albumin level and
      methicillin resistant Staphylococcus aureus (MRSA) pulmonary colonization.
      Regression analysis showed that BMI below the 10th percentile was associated with
      a 25.58% drop in FEV1, and plasma albumin levels equal to or lower than 4.1 mg/dL
      was associated with 18.6% FEV1 reduction. FEV1 was 14.4% lower in the MRSA
      infected patients. Plasma albumin of 4.25 mg/dL predicted FEV1 of 60% with 76.9%
      sensitivity and 72.2% specificity, and 85.7% accuracy. The socioeconomic status
      was not association with pulmonary function. CONCLUSION: BMI below the 10th
      percentile and albumin below 4.1 mg/dL were predictors of low FEV1. Chronic MRSA
      infection was associated with lower FEV1. Longitudinal studies may better
      complement these results.

PMID- 22411379
TI  - Waist circumference is better associated with high density lipoprotein (HDL-c)
      than with body mass index (BMI) in adults with metabolic syndrome.
AB  - BACKGROUND: The measurement of waist circumference (WC) is the most prevalent
      cause of the metabolic syndrome (MS). OBJECTIVE: The aim of this study was to
      correlate WC and BMI with high-density lipoprotein (HDL-c) levels in patients
      with MS being consulted by the Family Health Program (PSF), Brazil. METHODS: This
      cross-sectional study was conducted from September to November 2008 with 42
      patients (29 women and 13 men) from 35 to 77 years. Dietary intake was reported,
      and biochemical and body composition measures were taken. RESULTS: The HDL-c
      levels were higher in women when compared to men (48.4 +/- 8.1 mg/dL vs. 36.4 +/-
      7.8 mg/dL). However, the triglycerides (TG)/HDL-c ratio and TG concentrations
      were lower in women (3.8 +/- 1.5 and 178.0 +/- 57.8 mg/dL, respectively) than in
      men (9.4 +/- 8.5 and 471.5 +/- 501.5 mg/dL, respectively). Regarding skinfold
      profile, the triceps was greater in females (37.0 +/- 8.4 cm vs. 20.7 +/- 10.5
      cm). The dietetic profile showed that women had a lower intake of energy, fiber,
      phosphorus and sodium. The fruits and vegetables intake was diminished in the
      participants of this study, as less than 60% of the women and 50% of men met the
      daily recommendations. Approximately 54% of men and 28% of women had a lower
      intake of dairy products daily. Moreover, the results shows that the WC was
      negatively correlated to HDL-c (r = -0.41, p < 0.05) whereas the BMI is not
      associated with HDL-c (r = -0.34, p > 0.06). CONCLUSION: Our findings showed that
      WC is a better predictor of changes in HDL-c than BMI.

PMID- 22411380
TI  - [Development of questionnaire to assess food intake in the University of
      Antioquia, Colombia].
AB  - OBJECTIVE: To design a self-reported semi-quantitative questionnaire of frequency
      of food intake (QFFI) to assess the usual intake of foods and macronutrients of
      the academic community from the University of Antioquia (UoA). METHODOLOGY: The
      design of the questionnaire was done by reviewing and analyzing previous studies
      on food intake and the established linings for the selling of dietary products at
      the UoA. For selecting the foods and defining the serving size, we applied the
      criterion of intake pattern and the weight or size of the most frequent serving
      for each food, according to what has been reported in previous studies. We
      undertook a descriptive exploratory study with the QFFI including 154 people of
      the UoA. The analysis included the comprehension, applicability and
      comprehensiveness of the instrument for the participants, as well as the
      calculation of the descriptive parameters in the exploratory component. RESULTS:
      A semi-quantitative QFFI compounded by 144 foods classified in 9 groups with
      serving sizes known by the population and 9 categories of frequencies of usual
      intake within the last year. The exploratory study showed differences in the
      pattern of intake in the population groups analyzed. CONCLUSION: The designed
      QFFI was adequate for the study population since it was easily understood and
      administered, and it allowed for assessing the usual intake in the community of
      the UoA.

PMID- 22411381
TI  - [Assessment of the intervention in a therapeutic feeding center for children in
      Nicaragua].
AB  - INTRODUCTION: Child malnutrition carries a high morbimortality worldwide.
      Therapeutic feeding centers are essential in the treatment of malnourished
      children. OBJECTIVE: To evaluate the effectiveness of the therapeutic
      intervention in under-5 undernourished children in a Therapeutic Feeding Center.
      METHODS: A retrospective descriptive research was made through the revision of
      the clinical histories of children under 5 years that entered the Nutritional
      Recovery Center for Children in Matagalpa, Nicaragua, from January 2006 to July
      2010. RESULTS: Median age at admission was 17.2 months (p25:10.7-p75:27.2) and
      median stay in the center was 92 days (p25:61.5-p75:134.5). Prevalence of
      patients with severe acute malnutrition was 45%, moderate acute malnutrition 24%
      and risk for malnutrition 31%. At discharge 86% of patients were properly
      nourished. Median weight gain percentage after the first month in the center was
      15% (p25:12.6-p75:17.4). Median weight gain was 3.7 g/kg/day (p25:2.6-p75:5.4),
      being higher in children under 6 months (4.6 g/kg/day; p25:4.3-p75:7.5). Cured
      rate in the center was 87.5%, being the death rate 0% and the abandonment rate
      9%. DISCUSSION: The center evaluated works adequately, and fulfills the
      internationally recommended quality indicators. However, recommended average stay
      of 1-2 months and average weight gain of 8 g/kg/day are far of being fulfilled.
      Therefore, the Nutritional Recovery Center performs an effective intervention,
      but it's not efficient enough.

PMID- 22411382
TI  - Evaluation of the mini-nutritional assessment short-form (MNA-SF) among
      institutionalized older patients in Spain.
AB  - INTRODUCTION: In the present study, we evaluated a short form version of MNA test
      in a multicenter study and the relationship of different biochemical markers with
      MNASF scores. MATERIAL AND METHODS: This was a cross-sectional survey covering a
      sample of representative of the older institutionalized Spanish population aged
      above 65 years (n = 873). A Mini nutritional assessment short form test (MNA-SF)
      was used. RESULTS: The number of patients classified as well nourished (42.1%)
      was larger in the 65-74 (52.6%) range than in the 75-84 (40.2%), 85-94 (43.8%)
      and > 95 (24%) age ranges. Risk of undernutrition occurred in a total of 506
      patients (57.9%), risk of undernutrition was larger in > 95 (76%) range than in
      65-74 (47.4%), 75-84 (59.8%) and 85-94 range (56.2%). No differences were
      detected between males and females at risk of undernutrition (odds ratio: 0.85 CI
      95%: 0.64-1.12). CONCLUSION: In this multicenter study, institutionalized
      patients have a high prevalence of at risk of malnutrition assessed by MNA-SF
      test.

PMID- 22411383
TI  - [Subclinical hypothyroidism and cardiovascular risk factors].
AB  - OBJECTIVE: To determine the prevalence of subclinical hypothyroidism in the
      general population of an urban health center and describe the clinical
      characteristics and cardiovascular risk factors in patients with subclinical
      hypothyroidism. METHODS: An observational study, retrospective, reviewing the
      medical histories of patients sampled from June 2005 until July 2007. We analyzed
      the following variables; facts: age and sex. Family history thyroid disease and
      other diseases. Personal History: cardiovascular pulmonary autoimmune,
      alterations gynecology obstetric diabetes, hypertension (HT) dislipemia, obesity,
      psychiatric alterations and haematological. Laboratory data: novel TSH, free T4,
      antiperoxidase antibodies, total cholesterol and its fractions. RESULTS: The
      prevalence of the sample of 100 patients collected over 8 months was 3.8% in the
      general population over 14 years, of which 79 were women and 21 were men. 13%
      were type 2 diabetics, 23% had HT and 40% had dyslipidemia. Overweight and
      obesity were present in 26%. The average level of TSH was 6.92 +/- 2.29 MUU/ml
      and the average level of free T4 was 1.16 +/- 0.16 ng/ml. CONCLUSIONS: Prevalence
      subclinical hypothyroidism was 3.8%. especially in women with a mean age of 46.
      The incidence of cardiovascular risk factors in the subjects studied is higher in
      DM (13%), similar to general population in terms of dyslipidemia (40%) and
      obesity (23%) and lowest in hypertension (23%). In our study we observed a common
      pattern in the management of subclinical hypothyroidism, requiring the
      implementation and promotion of practice guidelines in primary care.

PMID- 22411384
TI  - Impact of functional dyspepsia on quality of life in eating disorder patients:
      the role of thought-shape fusion.
AB  - OBJECTIVE: The study begins by analysing the psychometric properties of the
      Nepean Dyspepsia Index-Short Form (NDI-SF), before moving on to study quality of
      life in patients with functional dyspepsia (FD) and the psychopathological
      features that underlie the disorder in three groups of subjects: patients with
      eating disorders (ED), psychiatric patients (non-ED), and a group of students,
      all of whom fulfilled Rome III criteria for FD. The analysis specifically focused
      on the relationship between thought-shape fusion (TSF) and functional dyspepsia,
      and hence on the potential repercussions this could have on the quality of life
      of patients with eating disorders. METHODS: The sample comprised 78 ED
      outpatients, 77 non-ED outpatients, and 90 university students, all of them with
      associated FD (Rome III criteria). The mental disorders (ED and non-ED) fulfilled
      the diagnostic criteria of DSM IV-RT. In all cases, the symptoms of dyspepsia,
      the related quality of life, anxiety, depression, and TSF were determined.
      RESULTS: Satiation and bloating were significantly higher in ED patients.
      Correlations between dyspepsia and TSF were initially positive and significant in
      all cases, but significance was only maintained in the group of ED patients after
      controlling for the other psychopathological variables. Regarding the ED group,
      the regression analysis revealed the following predictors of quality of life:
      dyspepsia, depressive symptomatology, TSF-conceptual, TSF-interpretative and
      total TSF. DISCUSSION: The cognitive distortion of TSF appears to constitute a
      general bias common to all eating disorders, with specific effect on the
      characteristic symptoms of FD.

PMID- 22411386
TI  - Paper and pencil vs online self-administered food frequency questionnaire (FFQ)
      applied to university population: a pilot study.
AB  - OBJECTIVE: To test the reliability of dietary intake data measured with an online
      food frequency questionnaires (FFQ) applied to a university population by
      comparing the results with those from a paper and pencil version. MATERIALS AND
      METHODS: A total of 50 students were recruited from the second-year Food
      Technology course at the Universitat Politecnica de Valencia (Comunidad
      Valenciana, Spain) in the academic year 2008-2009. The students were between the
      ages of 20-32. The participants completed both presentation modes of the FFQ
      (paper and pencil and online) in a cross-over study with a time interval of 3
      week. To study the effect of ordering of the questionnaires, participants were
      randomly assigned to group A (paper and pencil FFQ first) and group B (online FFQ
      first). Both self-administered semi-quantitative presentations of the FFQ
      included 84 food items divided into six groups (dairy products; eggs, meat and
      fish; vegetables, legumes and fruits; bread, cereals and similar; oils, fats and
      sweets; beverages and pre-cooked). Participants were asked how frequently and how
      much each food item they had consumed in the previous year. RESULTS: The response
      rate was 78% (39 students, 23% men and 77% women). For the total sample, the
      median dietary intakes were higher for the paper and pencil FFQ than the online
      version for energy (2,077 vs. 1,635 kcal/day), proteins (96 vs. 88 g/day),
      carbohydrates (272 vs. 211 g/day), and fat (70 vs. 58 g/day), respectively. These
      differences were statistically significant. However, there were not significant
      differences between the two presentations when the consumption by groups of food
      was calculated, except for "beverages and pre-cooked" group. CONCLUSIONS: The
      pilot testing showed that this online FFQ is a useful tool for estimating the
      intake of food groups in this university population. On the other hand, the
      differences found in the results of the absolute quantities of energy and
      nutrients intakes were not clear. These differences could be due to the problems
      that the participants had for reporting portion size in the paper and pencil FFQ
      as photographs of portion sizes were not presented.

PMID- 22411385
TI  - [Impact of a national treatment program in overweight adults women in primary
      care centers].
AB  - BACKGROUND: Chile has a high prevalence of overweight and obesity and is
      important to implement and evaluate treatment and control strategies that are
      effective. OBJECTIVES: To evaluate changes in nutritional status and fasting
      glucose in overweight women, pre-diabetic and/or pre-hypertension in primary care
      centers of public health sector. MATERIAL AND METHODS: A retrospective cohort of
      the universe of women admitted to the program in the participating primary care
      centers for 18 months was studied. Intervention includes consultations and
      workshops with doctors, nutritionists, psychologists and physical therapists for
      4 months, in primary heath center, promoting healthy eating and increased
      physical activity, not using drugs. Analysis of causes of admission, dropout,
      participation in scheduled activities and changes in baseline nutritional status
      and fasting glucose after 4 months of intervention. RESULTS: 1,528 women 18 to 65
      years old, with initial BMI between 25 and 40 were studied and 1,222 completed
      treatment (71.6%). The median weight change was -3.9% (CI -4.1 to 3.7) of initial
      weight and -2.0 mg/dl (CI -2.0 to 1.0) of blood glucose. 36.8% of patient
      decreased >= 5% of initial weight, 12.5% of overweight and about one third of
      obese partly improved or normalized their nutritional status. There was
      significant reduction in the prevalence of pre-diabetes (16.6 to 8.8%, p <
      0.001). CONCLUSION: The intervention was effective for good adhesion and impact
      in reducing cardiovascular risk factors as BMI, waist circumference and high
      fasting glucose. One challenge is to keep track of this population to ascertain
      the impact in the medium and long term.

PMID- 22411387
TI  - [Efficacy evaluation of an oral powder supplement enriched with eicosapentaenoic
      acid in cancer patients].
AB  - BACKGROUND AND OBJECTIVES: The beneficial effect of eicosapentaenoic acid in
      cancer patients is widely described especially in relation to its role in tumour
      cachexia. The aim of the study was to evaluate the efficacy of administration of
      a new oral powder supplement enriched with eicosapentaenoic acid compared to a
      standard liquid supplement in cancer patients. PATIENTS AND METHODS: A total of
      61 cancer patients, aged more than 18 years, were randomized to receive during a
      month a bonus of 600 kcal/ day to their regular diet with an oral powder
      supplement enriched with eicosapentaenoic acid (1.5 g) (RSI) or with a standard
      liquid supplement (RE). The following data were collected at baseline and after
      one month: the Patient-Generated Subjective Global Assessment (pg-SGA),
      anthropometric measurements (skin folds, circumferences and bioimpedance),
      dietary parameters (3-day food record), biochemical and inflammatory parameters
      (basic biochemistry, cytokines, prealbumin and Reactive C Protein). Quality of
      life was evaluated using the SF-36 questionnaire. At the end, scales were used to
      asses sensory perception, tolerance and satiety induced by the products and
      motivation to eat. RESULTS: 40 patients completed the study. After intervention,
      anthropometric parameters do not change and prealbumin values increased
      significantly in both groups (RSI 16.11 +/- 5.66 mg/dl vs. 19.81 +/- 6.75 mg/dl p
      < 0.05 and RE 6.13 +/- 16.55 mg/dl vs. 19.03 +/- 5.47 mg / dl p < 0.05). RSI
      group significantly decreased interferon gamma (INF-gamma) values (0.99 +/- 0.95
      vs. 0.65 +/- 0.92 pg/ml, p < 0.05). In contrast, RE group increased INF-gamma
      after intervention (1.62 +/- 1 27 vs. 2.2 +/- 3.19 pg/ml, p < 0.05). There were
      no significant differences in hunger, appetite, satiety and intake capacity in
      both groups. The SF-36 scores improved in both groups. CONCLUSIONS:
      Supplementation based on an oral powder formula enriched with 1.5 g EPA during
      one month in cancer patients improved certain inflammatory parameters. This
      product may be a novel and valuable option to be added to the nutritional
      intervention strategies used for cancer patients.

PMID- 22411388
TI  - Site-specific circadian expression of leptin and its receptor in human adipose
      tissue.
AB  - INTRODUCTION: Circadian variability of circulating leptin levels has been well
      established over the last decade. However, the circadian behavior of leptin in
      human adipose tissue remains unknown. This also applies to the soluble leptin
      receptor. OBJECTIVE: We investigated the ex vivo circadian behavior of leptin and
      its receptor expression in human adipose tissue (AT). SUBJECTS AND METHODS:
      Visceral and subcutaneous abdominal AT biopsies (n = 6) were obtained from morbid
      obese women (BMI >= 40 kg/m2). Anthropometric variables and fasting plasma
      glucose, leptin, lipids and lipoprotein concentrations were determined. In order
      to investigate rhythmic expression pattern of leptin and its receptor, AT
      explants were cultured during 24-h and gene expression was analyzed at the
      following times: 08:00, 14:00, 20:00, 02:00 h, using quantitative real-time PCR.
      RESULTS: Leptin expression showed an oscillatory pattern that was consistent with
      circadian rhythm in cultured AT. Similar patterns were noted for the leptin
      receptor. Leptin showed its achrophase (maximum expression) during the night,
      which might be associated to a lower degree of fat accumulation and higher
      mobilization. When comparing both fat depots, visceral AT anticipated its
      expression towards afternoon and evening hours. Interestingly, leptin plasma
      values were associated with decreased amplitude of LEP rhythm. This association
      was lost when adjusting for waist circumference. CONCLUSION: Circadian
      rhythmicity has been demonstrated in leptin and its receptor in human AT cultures
      in a site-specific manner. This new knowledge paves the way for a better
      understanding of the autocrine/paracrine role of leptin in human AT.

PMID- 22411390
TI  - Attitudinal determinants of fish consumption in Spain and Poland.
AB  - OBJECTIVE: To identify attitudinal determinants of fish consumption in Spain and
      Poland, and to discuss the potential impact of local healthy eating policies in
      the observed reported frequency of fish consumption. DESIGN: Repeated survey
      analysis , multivariate linear regression analysis. Data collected through a
      questionnaire that included socio-demographics, self-reported anthropometrics, as
      well as validated items of attitudinal and involvement scales, validated items of
      knowledge about fish, and behaviours (reported fish consumption). SETTING:
      Consumer survey in Poland and Spain, 1800 respondents in 2004 and 1815
      respondents in 2008. RESULTS: In Poland, intentions to consume more fish and
      reported fish consumption increased in the four years period between both
      surveys, together with objective knowledge regarding fish. In Spain with the
      exception of subjective knowledge, fish consumption at home and total fish
      consumption, all attitudinal and involvement scale changes were statistically
      significant. Multivariate regression revealed that age had a small but
      significant positive effect in all scales, except for satisfaction with life,
      fish consumption out of home and subjective health. Satisfaction with life and
      subjective knowledge were significantly determined by household size. The
      differences between countries were statistically significant for involvement with
      health and fish, for intention to eat fish, the general attitudes and objective
      knowledge regarding fish. CONCLUSIONS: In Poland, a more positive attitude
      towards fish, and increased levels of knowledge about this product were observed
      and could partially be attributed to national policy efforts. In Spain, an
      interesting feature was observed: more people reported choosing fish when eating
      out in 2008 compared with respondents in 2004. Such a trend suggests that people
      slowly move towards healthier choices even in the out of home eating.

PMID- 22411389
TI  - Experimental induction of thought-shape fusion in eating disorder patients: the
      role of coping strategies.
AB  - OBJECTIVE: The aim was to induce the thought-shape fusion (TSF) distortion
      experimentally, testing: a) Whether the TSF distortion could be induced by
      anxiety in general or if it had a specific relationship with thoughts related to
      the intake of fattening foods; b) Whether the TSF could be induced in non
      clinical participants as well as in the eating disorder patients; c) Whether
      participants with more appropriate coping strategies would experience less TSF
      than those who showed inadequate coping strategies; and d) That TSF could have
      behavioural effects (e.g., neutralization of TSF and food intake) related to
      emotions. METHODS: The sample comprised two groups (eating disorder patients and
      students), with 45 participants each, aged between 18 and 25 years, 92.50% and
      86.7% of women in the eating disorders group and the students group respectively.
      The two groups underwent three experimental conditions (TSF, anxiety, and
      control), measuring the results with regards to the emotional and behavioural
      responses. RESULTS: Participants in the TSF induction condition reported more
      guilt, more feelings of fatness, more likelihood of weight gain, and higher
      degree of moral wrong-doing compared with participants in both the anxiety and
      control induction conditions. The effect of the adequate coping strategies in
      decreasing the strength of the TSF bias was confirmed in both eating disorder
      patients and non-clinical participants. DISCUSSION: The study of the TSF
      distortion may have relevant implications in terms of treatment and prognostic of
      eating disorders. This distortion may be involved in the development and
      maintenance of eating disorder psychopathology.

PMID- 22411391
TI  - A comparison of fat mass and skeletal muscle mass estimation in male ultra
      endurance athletes using bioelectrical impedance analysis and different
      anthropometric methods.
AB  - Two hundred and fifty seven male Caucasian ultra-endurance athletes were
      recruited, pre-race, before different swimming, cycling, running and triathlon
      races. Fat mass and skeletal muscle mass were estimated using bioelectrical
      impedance analysis (BIA) and anthropometric methods in order to investigate
      whether the use of BIA or anthropometry would be useful under field conditions.
      Total body fat estimated using BIA was significantly high (P < 0.001) compared
      with anthropometry. When the results between BIA and anthropometry were compared,
      moderate to low levels of agreement were found. These results were in accordance
      with the differences found in the Bland-Altman analysis, indicating that the
      anthropometric equation of Ball et al. had the highest level of agreement (Bias =
      -3.0 +/- 5.8 kg) with BIA, using Stewart et al. (Bias = -6.4 +/- 6.3 kg),
      Faulkner (Bias = -4.7 +/- 5.8 kg) and Wilmore-Siri (Bias = -4.8 +/- 6.2 kg). The
      estimation of skeletal muscle mass using BIA was significantly (P < 0.001) above
      compared with anthropometry. The results of the ICC and Bland-Altman method
      showed that the anthropometric equation from Lee et al. (Bias = -5.4 +/- 5.3 kg)
      produced the highest level of agreement. The combined method of Janssen et al.
      between anthropometry and BIA showed a lower level of agreement (Bias = -12.5 +/-
      5.7 kg). There was a statistically significant difference between the results
      derived from the equation of Lee et al. and Janssen et al. (P < 0.001). To
      summarise, the determination of body composition in ultra-endurance athletes
      using BIA reported significantly high values of fat and skeletal muscle mass when
      compared with anthropometric equations.

PMID- 22411392
TI  - [Risk factors of bloodstream infections associated with parenteral nutrition in
      pediatric patients].
AB  - INTRODUCTION: One of the complications of parenteral nutrition (PN) is
      bloodstream infection (BSI) associated with catheter, unknown the most important
      risk factors in our country. OBJECTIVE: To determine risk factors of BSI
      associated with PN in pediatric patients in public hospitals of Santiago, Chile.
      PATIENTS AND METHODS: In two public hospitals all newborns and children receiving
      PN were analyzed retrospectively, from January 2002 to December 2005. The study
      group (SG) was formed by all those with blood cultures (+) during the
      administration of PN. We selected two controls for each case, children with PN
      and blood cultures (-) (control group, CG). We used parametric, nonparametric and
      logistic regression to analyze data. RESULTS: There were 58 cases and 130
      controls. Children of the SG received PN for longer days than CG: 24 (7-934) vs.
      10 days (7-152) (p < 0.001), presented a higher rate of malnutrition (44.4% vs.
      31%, chi2, p < 0.05) and received more frequently PN by central venous catheter
      than peripheral catheter (GE: 60.3% and 6.9% vs. GC: 40.9% and 16.9%
      respectively, chi2, p < 0.01), without differences between newborns and older
      children. The stepwise logistic regression showed that the only significant
      variable was the duration of PN in weeks (OR: 1.55,95% CI 1.28 to 1.9; p < 0,05).
      CONCLUSIONS: The blood stream infections associated with parenteral nutrition in
      children in public hospitals of Santiago, are associated with longer duration of
      parenteral nutrition and in less degree to the child's nutritional compromise.

PMID- 22411393
TI  - [Home parenteral nutrition (HPN): feasibility of its implementation from a public
      hospital].
AB  - INTRODUCTION: The intensive care of patients at home had probed important
      beneficialness for the patient and the Health System. There are very few
      experiences of this kind of care from the Public Hospitals. OBJECTIVE: To develop
      a social-sanitary analysis of the feasibility of the implementation of HPN on
      patients with short bowel syndrome (SBS) from a Public Hospital. MATERIAL AND
      METHODS: Patients hospitalized between 1985-2009 were included. We analyzed: age,
      residual intestine length (RIL), time between de indication and the beginning of
      HPN, HPN duration, treatment modality and clinical outcome. Social determinants:
      home place, habitat conditions, employment conditions, educational level, social
      security and Low Socioeconomic Status (LSS). The group were divided in two: 1-
      patients with feasibility of HPN when it was prescribed; 2- patients without
      feasibility of HPN. RESULTS: 61 patients were included, RIL x: 21.7 +/- 11.6 cm.
      The HPN was feasible (G1) in 32 patients (52.4%) and no feasible (G2) in 29
      (47.6%). The home treatment modality was in self-caring 25 (81%) and with nurses
      support 7 (19 %). The social determinants associated with the HPN feasibility
      were: more than one takecare (p 0.03), educational level (p 0.01), adequate
      habitat conditions (p 0.02) and Low Socioeconomis Status (LSS) (p 0.07). 17
      patients reached intestinal adaptation (28%), 6 (10%) were transplanted, 19 (31%)
      died and 19 (31%) are actually on HPN. CONCLUSION: The HPN realized from the
      Public Hospital is feasible. Different social determinants were observed. The
      care of this group of patients must be done by an interdisciplinary group
      including general aspects of the child and the family.

PMID- 22411394
TI  - Design of a self-administered online food frequency questionnaire (FFQ) to assess
      dietary intake among university population.
AB  - OBJECTIVE: To introduce and describe a new tool called UPV-FFQ to evaluate
      dietary intake of the university population. The new tool consists principally in
      a self-administered online food frequency questionnaire (FFQ). MATERIALS AND
      METHODS: The tool UPV-FFQ has been developed by means of web pages applying the
      technology ASP.NET 2.0 and using the database SQL Server 2005 as support. To
      develop the FFQ has been used as model the paper and pencil FFQ called "Dieta,
      salud y antropometria en la poblacion universitaria". RESULTS: The tool has three
      parts: (1) a homepage, (2) a general questionnaire and (3) a FFQ. The FFQ has a
      closed list of 84 food items commonly consumed in Valencia region. The
      respondents has to indicate the food items that they consume (2 possible
      options), the frequency of consumption (9 response options) and the quantity
      consumed (7 response options). The UPV-FFQ has approximately 250 color
      photographs that represents to three portion sizes. The photographs are useful to
      help the respondents to choose the portion sizes that more adjusts to their
      habitual portions. The new tool provides quantitative information of the habitual
      intake of 31 nutritional parameters and provides qualitative information of the
      general questionnaire. A pilot study was done for a total of 57 respondents. The
      media time spend to fill in was 15 minutes. CONCLUSIONS: The pilot study
      concluded that the questionnaire was ease-of-use, low cost and time-effectiveness
      questionnaire. The format and the sequence of the questions were easily
      understood.

PMID- 22411395
TI  - Effects of maternal glucose tolerance, pregnancy diet quality and neonatal
      insulinemia upon insulin resistance/sensitivity biomarkers in normoweight
      neonates.
AB  - INTRODUCTION: Differences in neonatal insulin sensitivity/ resistance markers due
      to the maternal impaired glucose tolerance (IGT) have not been tested. The
      Healthy Eating Index (HEI) score has been employed for evaluating pregnancy diet
      quality. AIMS: To study, the effect of neonatal insulinemia, maternal IGT and
      diet HEI score upon insulin sensitivity/ resistance at birth. METHODS: 176
      singleton, normoweight, full-term, Caucasian Spanish neonates, delivered without
      fetal distress whose mothers were screened for gestational IGT were studied.
      Quantitative Insulin Sensitivity Check Index (QUICKI) and Homeostatic Model
      Assessment (HOMAIR) were calculated. Diet followed during the third month of
      pregnancy was recorded and the respective HEI score calculated in a sample of 29
      mothers. RESULTS: As quartile for cord blood insulin levels increased, glucose,
      the insulin/cortisol ratio and HOMA-IR (all p < 0.001) and IGF-I (p < 0.01)
      increased while QUICKI and the glucose/insulin ratio (both p < 0.001) and GH (p <
      0.05) decreased. Neonates from IGT mothers had higher insulin, HOMA-IR (both p <
      0.01) and insulin/cortisol ratio (p < 0.05) and lower GH, QUICKI (both p < 0.01)
      and glucose/ insulin ratio (p < 0.05) than their normal maternal glucose
      tolerance (NGT) counterparts. Neonatal insulinemia influences more than IGT on
      the insulin resistance/sensitivity markers at birth. Mothers of hyperinsulinemic
      neonates showed lower HEI scores (p < 0.05). CONCLUSION: A large percentage of
      full-term normoweight infants with hyperinsulinemia showed altered insulin
      resistance markers. Their mothers consumed low quality diets. Screening
      strategies focused on neonatal glycemia and insulinemia together with maternal
      nutritional assessment and advice during pregnancy should be considered.

PMID- 22411396
TI  - Nutritional status of zinc and activity superoxide dismutase in chronic renal
      patients undergoing hemodialysis.
AB  - INTRODUCTION: Chronic kidney disease promotes changes in the zinc nutritional
      status and in the antioxidant defense system. This study assessed the
      relationship between the parameters of the zinc nutritional status and the
      activity of superoxide dismutase in patients with chronic renal failure who are
      receiving hemodialysis. METHODS: 134 individuals, aged between 18 and 85 years,
      were divided into two groups: case group (hemodialyzed patients, n = 63) and
      control group (n = 71). Zinc concentrations in plasma and erythrocytes were
      determined using the flame atomic absorption spectrophotometry technique. The
      activity of superoxide dismutase enzyme was determined according to Ransod kit.
      RESULTS: The mean values of plasma zinc were 62.02 +/- 13.59 MUg/dL and 65.58 +/-
      8.88 MUg/dL, and for erythrocytary zinc the values were 54.52 +/- 22.82 MUgZn/gHb
      and 48.01 +/- 15.08 MUgZn/gHb for the chronic renal patients and the control
      group, respectively. The activity of superoxide dismutase was significantly lower
      in patients when compared with the control group (p < 0.05). CONCLUSION: The
      activity of superoxide dismutase in patients with chronic renal failure
      undergoing hemodialysis, which is influenced by zinc concentracions, was
      significantly lower. There was an inadequate response of this enzyme to oxidative
      stress in patients undergoing hemodialysis.

PMID- 22411397
TI  - [Vitamin A and zinc levels in gastroenterological surgical patients: Relation
      with inflammation and postoperative complications].
AB  - INTRODUCTION: It is accepted that even mild nutrient depletion may affect the
      evolution of the surgical patient. OBJECTIVE: To evaluate the influence of
      preoperative levels of plasma retinol and zinc on postoperative evolution of
      surgical patients; to evaluate the influence of inflammation on both level
      markers. METHODS: Plasma retinol and zinc were determined in 50 patients before
      programmed gastroenterological surgeries. To detect global malnutrition BMI and
      weight loss percentage (WL%) were included. C-reactive protein (CRP) was included
      as inflammation marker. During follow up postoperative complications were
      recorded. The present analysis was carried out in 43 patients with complete
      information. RESULTS: Low retinol values (< 20 MUg/dl) were founded in 3 cases
      and low Zn values (< 85 MUg/dl) in 20 cases, being 9 of them indicative of severe
      deficiency (< 70 MUg/dl). Postoperative complications were recorded in 17
      patients; patients with complications presented lower values of plasma Zn (78.4
      +/- 25.8 vs. 87.8 +/- 25.7 MUg/dl) and retinol (36.9 +/- 14.5 vs. 49.7 +/- 20.6;
      P = 0.0318) than those with no complications; the number of patients with
      complications decreased when retinol and Zn ranges increased. No relation between
      BMI or WL% and appearance of complications was founded; patients with higher WL%
      were those with higher usual weight. Inflammation affected both markers: retinol
      dropped from 50.1 +/- 17.2 to 44.0 +/-20.8 and to 23.7 +/- 4.0 MUg/dl for CRP
      ranges of < 0.5, 0.5-3.9 and >= 4 mg/dl, respectively (p = 0.0193); levels of
      zinc fell from 90.1 +/- 17.8 to 85.2 +/- 29.9 and to 55.0 +/- 25.9 MUg/dl for the
      same CRP ranges (P = 0.0195). Zn level influenced retinol level, dropping to 33.1
      +/- 11.7 MUg/dl of retinol in the Zn severe deficiency group (P = 0.0386).
      CONCLUSIONS: The obtained results confirm the influence of vitamin A and zinc on
      postoperative evolution of the surgical patient, while alert about the
      interrelationships among vitamin A, zinc and inflammation, which lead to
      difficulty to establish the real source of deficiencies. Beyond these
      difficulties, retinol and zinc plasma levels determine the nutrient availability
      for the body and appear as promissory markers of surgical risk.

PMID- 22411398
TI  - [Nutritional support outcomes in critical care].
AB  - BACKGROUND & AIMS: To revise the effect of our nutritional support practices on
      outcomes from critical care patients and propose new study hypothesis. METHODS:
      Retrospective observational study was conducted in all critically ill patients
      who had been prescribed nutritional support, through a year time, in an Intensive
      Care Unit. The nutritional support practices are described. Severity of illness
      (Simplified Acute Physiology Score II), timing and route of nutritional support,
      prescribed and delivered daily caloric intake for a maximum of 7 days, medical or
      surgical patient, length of stay in ICU, incidence rate and incidence density of
      nosocomial infections, and presence of gastrointestinal complications were
      recorded. Relationships between timing and route of nutritional support and
      percentage of received/ prescribed calories with mortality, nosocomial
      infections, days of mechanical ventilation and length of stay in the Intensive
      Care Unit were studied. RESULTS: 102 patients of our intensive care patients
      received nutritional support and were selected for the study. EN was used in 42
      patients (41%), 41 (40%) received TPN and 19 patients (19%) received mixed
      nutrition. Timing of nutritional support showed a mean of 3.1 +/- 1.9 days and
      was statistically different between patients who survived or died (2.82 +/- 1.65
      vs. 3.74 +/- 2.33 days). Patients received 58 +/- 28% of their requirements but
      this data did not show any difference with mortality and morbidity. There was a
      statistical difference between the route of nutrition and the following data:
      type of patient, caloric intake in the study period, length of stay in ICU and
      days of mechanical ventilation. CONCLUSIONS: Our study demonstrates that
      nutritional support patients are more severely ill than nonnutritional support
      patients. Timing of nutritional support was shorter in survivors. Our study
      confirms a low caloric input in the critically ill patient during the first week
      of illness, especially in the enteral nutrition group. However this finding was
      not associated with mortality or morbidity. Parenteral route did show better
      clinical outcomes than enteral or mixed nutrition. Our findings suggest that a
      moderate and early caloric intake could obtain better outcomes, independently of
      the route of nutritional support.

PMID- 22411399
TI  - [Resistance training reduces the metabolic acidosis and hepatic and renal
      hypertrophy caused by the consumption of a high protein diet in rats].
AB  - INTRODUCTION: High protein (HP) diet consumption may adversely affect metabolic
      acidosis and hepatic and renal health. Despite such potentially adverse effect,
      there are only few studies analyzing the effects of resistance training on the
      parameters that could be altered by such diets. MATERIAL AND METHODS: A total of
      32 adult male Wistar rats were randomly distributed in 4 experimental groups (n =
      8): normoprotein or HP diets, with or without resistance training. Diets were
      based on a whey protein hydrolyzate, and the experimental period lasted for 90
      days. RESULTS AND DISCUSSION: Consumption of HP diets and resistance training
      significantly affected food intake, body composition and plasmatic levels of
      total cholesterol and triglycerides. Consumption of HP diets led to a
      considerable increase in liver and kidney weight (P < 0.001), urinary volume and
      acidity, as well as in the urinary excretion of Ca, with a parallel reduction in
      the urinary excretion of citrate (P < 0.05). The buffering action of resistance
      training on such diet-induced alterations was especially evident in the levels of
      hepatic and plasma triglycerides, plasmatic urea, and in liver and kidney weight
      (P < 0.001). CONCLUSION: Resistance training had a protective action against
      alterations of hepatic and renal health status and some metabolic parameters like
      hepatic and plasma triglycerides.

PMID- 22411400
TI  - [Protein-losing gastroenteropathy: unremembered cause of hypoalbuminemia?].
AB  - Protein-losing gastroenteropathy (PLE) consists on an active digestive tract
      protein loss syndrome and it is related to some diseases. After a wide research
      into bibliography (MEDLINE - Pubmed),we have found few references to this
      gastroenteropathy as a cause of hypoalbuminemia related to malnutrition. This has
      motivated us to review this entity, detailing some recent clinical cases of our
      experience.

PMID- 22411401
TI  - [Cellulase in the treatment of phytobezoars].

PMID- 22411402
TI  - [Colorectal cancer prevention with diet and physical activity: recent update].

PMID- 22411403
TI  - [Ethics and scientific publication].

PMID- 22411404
TI  - Two isomorphous Mn(II) and Co(II) 5-amino-tetrazolate coordination polymers with
      magnetic Delta-chains: crystal structures and magnetic properties.
AB  - Two Co(II) and Mn(II) coordination polymers, which have been synthesized under
      hydrothermal conditions, are isomorphous with magnetic Delta-chains containing
      trinuclear triangular [M(3)(MU(3)-OH)] clusters. The Delta-chains are bridged by
      isonicotinic spacers to generate a two-dimensional scalariform layer structure.
      Magnetic investigations indicate that Co(II) compound exhibits not only spin
      canting but also metamagnetic behaviors, while only spin-canted antiferromagnetic
      behaviors was observed in Mn(II) compound.

PMID- 22411407
TI  - Exome and whole-genome sequencing for gene discovery: the future is now!

PMID- 22411408
TI  - Fold of the conserved DTC domain in Deltex proteins.
AB  - Human Deltex 3-like (DTX3L) is a member of the Deltex family of proteins.
      Initially identified as a B-lymphoma and BAL-associated protein, DTX3L is an E3
      ligase that regulates subcellular localization of its partner protein, BAL, by a
      dynamic nucleocytoplasmic trafficking mechanism. Unlike other members of the
      Deltex family of proteins, DTX3L lacks the highly basic N-terminal motif and the
      central proline-rich motif present in other Deltex proteins, and instead contains
      other unique N-terminal domains. The C-terminal domains are, however, homologous
      with other members of the Deltex family of proteins; these include a RING domain
      and a previously unidentified C-terminal domain. In this study, we report the
      high-resolution crystal structure of this previously uncharacterized C-terminal
      domain of human DTX3L, which we term the Deltex C-terminal domain.

PMID- 22411409
TI  - Virtual reality simulation: using three-dimensional technology to teach nursing
      students.
AB  - The use of computerized technology is rapidly growing in the classroom and in
      healthcare. An emerging computer technology strategy for nursing education is the
      use of virtual reality simulation. This computer-based three-dimensional
      educational tool simulates real-life patient experiences in a risk-free
      environment, allows for repeated practice sessions, requires clinical decision
      making, exposes students to diverse patient conditions, provides immediate
      feedback, and is portable. The purpose of this article was to review the
      importance of virtual reality simulation as a computerized teaching strategy. In
      addition, a project to explore readiness of nursing faculty at one major
      Midwestern university for the use of virtual reality simulation as a computerized
      teaching strategy is described where faculty thought virtual reality simulation
      would increase students' knowledge of an intravenous line insertion procedure.
      Faculty who practiced intravenous catheter insertion via virtual reality
      simulation expressed a wide range of learning experiences from using virtual
      reality simulation that is congruent with the literature regarding the barriers
      to student learning. Innovative teaching strategies, such as virtual reality
      simulation, address barriers of increasing patient acuity, high student-to
      faculty ratio, patient safety concerns from faculty, and student anxiety and can
      offer rapid feedback to students.

PMID- 22411410
TI  - Implementing a competency-based electronic portfolio in a graduate nursing
      program.
AB  - Use of electronic portfolios (e-portfolios) has been advocated to demonstrate
      nursing student accomplishments as well as to document program and course
      outcomes. This use of e-portfolios incorporates information technology, thus
      aligning the educational process in professional degree programs to 21st-century
      teaching and learning scholarship. Here we describe a project to explore the
      feasibility of transitioning from documenting student competencies in hard-copy
      binders to e-portfolios. To make this transition in an efficient manner in our
      graduate nursing program, we used the Plan, Do, Study, Act quality-improvement
      model. An interdisciplinary team of nursing faculty and educational computing
      consultants developed a professional e-portfolio template and implemented a pilot
      program for 10 students enrolled in our nurse educator specialty. This program
      was executed by assessing university resources, evaluating the technological
      competence of both students and faculty, and through the interdisciplinary team
      members' commitment to provide ongoing support for the program.

PMID- 22411411
TI  - Examining the functionality of the DeLone and McLean information system success
      model as a framework for synthesis in nursing information and communication
      technology research.
AB  - In this review, studies examining information and communication technology used
      by nurses in clinical practice were examined. Overall, a total of 39 studies were
      assessed spanning a time period from 1995 to 2008. The impacts of the various
      health information and communication technology evaluated by individual studies
      were synthesized using the DeLone and McLean's six-dimensional framework for
      evaluating information systems success (ie, System Quality, Information Quality,
      Service Quality, Use, User Satisfaction, and Net Benefits). Overall, the majority
      of researchers reported results related to the overall Net Benefits (positive,
      negative, and indifferent) of the health information and communication technology
      used by nurses. Attitudes and user satisfaction with technology were also
      commonly measured attributes. The current iteration of DeLone and McLean model is
      effective at synthesizing basic elements of health information and communication
      technology use by nurses. Regardless, the current model lacks the sociotechnical
      sensitivity to capture deeper nurse-technology relationalities. Limitations and
      recommendations are provided for researchers considering using the DeLone and
      McLean model for evaluating health information and communication technology used
      by nurses.

PMID- 22411412
TI  - Development of a conceptual framework to guide a program of research exploring
      nurse-to-nurse communication.
AB  - Research in nursing informatics has been described as problem based rather than
      theory guided. Furthermore, few examples exist in the literature where the
      process of theory development is described. This article describes a process used
      to develop a conceptual framework that supports a theory-driven program of
      research in nursing informatics. The conceptual framework combines Symbolic
      Interaction Theory and Information Theory. Constructs of Symbolic Interaction
      Theory (mind, self, and society) and Information Theory (entropy, negentropy,
      redundancy, probability, and noise) were then organized according to Gerbner's
      Communication Model. Theory derivation was the method used for organizing
      abstract constructs and reducing them to a measurable level. Theory derivation
      was supplemented with initial research findings. The measurable or middle-range
      constructs were then organized in a meaningful manner for conceptual framework
      development. The use of theory derivation to develop a conceptual framework to
      support theory-driven nursing informatics research will be discussed. The
      framework entitled "Effective Nurse-to-Nurse Communication" that guides a program
      of research will then be presented.

PMID- 22411413
TI  - Developing iCare v.1.0: an academic electronic health record.
AB  - An electronic health record application, iCare v.1.0, was developed and tested
      that allows data input and retrieval while tracking student performance over
      time. The development and usability testing of iCare v.1.0 followed a rapid
      prototyping software development and testing model. Once the functionality was
      tested by engineers, the usability and feasibility testing began with a
      convenience sample of focus group members including undergraduate and graduate
      students and faculty. Three focus groups were created, and four subjects
      participated in each focus group (n = 12). Nielsen's usability heuristics and
      methods of evaluation were used to evaluate data captured from each focus group.
      Overall, users wanted a full-featured electronic health record with features that
      coached or guided users. The earliest versions of iCare v.1.0 did not provide
      help features and prompts to guide students but were later added. Future versions
      will incorporate a full-featured help section. The interface and design of iCare
      v.1.0 are similar to professional electronic health record applications. As a
      result of this usability study, future versions of iCare will include more robust
      help features along with advanced reporting and elements specific to specialty
      populations such as pediatrics and mental health services.

PMID- 22411414
TI  - The influence of integrated electronic medical records and computerized nursing
      notes on nurses' time spent in documentation.
AB  - We investigated nurses' time spent in documentation as it relates to the use of
      electronic charting. A cross-sectional analysis was completed using time and
      motion data collected during a nursing process improvement initiative for 105
      units in 55 hospitals. Ordinary least squares regression with a cluster
      adjustment revealed very little difference in time spent in documentation with or
      without the use of electronic medical records or computerized nursing notes.
      Nurses spent 19% of their time completing documentation, regardless of electronic
      charting usage, compared with all other categories of care. These findings
      suggest that integrated electronic medical records and computerized nursing notes
      do not appear to increase the time nurses spend documenting.

PMID- 22411415
TI  - Criteria for quantitative and qualitative data integration: mixed-methods
      research methodology.
AB  - Many studies have emphasized the need and importance of a mixed-methods approach
      for evaluation of clinical information systems. However, those studies had no
      criteria to guide integration of multiple data sets. Integrating different data
      sets serves to actualize the paradigm that a mixed-methods approach argues; thus,
      we require criteria that provide the right direction to integrate quantitative
      and qualitative data. The first author used a set of criteria organized from a
      literature search for integration of multiple data sets from mixed-methods
      research. The purpose of this article was to reorganize the identified criteria.
      Through critical appraisal of the reasons for designing mixed-methods research,
      three criteria resulted: validation, complementarity, and discrepancy. In
      applying the criteria to empirical data of a previous mixed methods study,
      integration of quantitative and qualitative data was achieved in a systematic
      manner. It helped us obtain a better organized understanding of the results. The
      criteria of this article offer the potential to produce insightful analyses of
      mixed-methods evaluations of health information systems.

PMID- 22411416
TI  - Impact of electronic health records on nurses' productivity.
AB  - As the use of electronic health records increases, it becomes necessary to
      address their global impact on nurses' productivity in hospitals. A retrospective
      cross-sectional study was conducted to explore the impact of electronic health
      records on nurses' productivity and to examine whether the impacts are moderated
      through case-mix index or adjusted patient-days. Two sources of data were linked
      and analyzed for years 2007 and 2008: the American Hospital Association survey
      and the Centers for Medicare & Medicaid Services data. Almost two-thirds of the
      respondent hospitals in both years (63.9% in 2007 and 68.4% in 2008) had a high
      electronic health record index (>=5). Hospitals with higher penetration of
      electronic health records had more RNs employed (coefficient=0.234, P=.002)
      compared with hospitals with low penetration of electronic health records, even
      when controlling for adjusted patient-day volumes. This difference decreased for
      hospitals with higher case-mix index values. The study findings fail to suggest
      any financial savings or superior productivity in nurses due to usage of
      electronic health records.

PMID- 22411417
TI  - Community-based, interdisciplinary geriatric care team satisfaction with an
      electronic health record: a multimethod study.
AB  - This multimethod study measured the impact of an electronic health record (EHR)
      on clinician satisfaction with clinical process. Subjects were 39 clinicians at a
      Program of All-inclusive Care for Elders (PACE) site in Philadelphia utilizing an
      EHR. Methods included the evidence-based evaluation framework, Health Information
      Technology Research-Based Evaluation Framework, which guided assessment of
      clinician satisfaction with surveys, observations, follow-up interviews, and
      actual EHR use at two points in time. Mixed-methods analysis of findings provided
      context for interpretation and improved validity. The study found that clinicians
      were satisfied with the EHR; however, satisfaction declined between time periods.
      Use of EHR was universal and wide and was differentiated by clinical role.
      Between time periods, EHR use increased in volume, with increased timeliness and
      decreased efficiency. As the first EHR evaluation at a PACE site from the
      perspective of clinicians who use the system, this study provides insights into
      EHR use in the care of older people in community-based healthcare settings.

PMID- 22411418
TI  - Therapeutic plasma exchange in anti-N-methyl-D-aspartate-receptor (anti-NMDA-R)
      encephalitis associated with benign ovarian teratoma.

PMID- 22411419
TI  - Transurethral intraprostatic Botulinum toxin-A injection: a novel treatment for
      BPH refractory to current medical therapy in poor surgical candidates.
AB  - PURPOSE: Benign prostatic hyperplasia (BPH) is the main cause of lower urinary
      tract symptoms (LUTS) in elderly men. Some patients respond poorly to routine
      medical therapy and are not well suited for surgery, too. This study was planned
      to evaluate the effect of Botulinum-A on BPH refractory to current medical
      therapy in poor surgical candidates. METHODS: In this clinical trial, 10 patients
      with LUTS suggestive of BPH who had responded poorly to medical therapy for at
      least 6 months and were poor surgical candidates, were received different doses
      of transurethral Botulinum-A injection based on their prostate volume. The
      prostate volume, PSA, Qmax, IPSS, PVR and frequency of nocturia were evaluated
      and compared before and after treatment. RESULTS: The mean IPSS was 24.50 +/- 3.8
      and 13.40 +/- 2.67 before and after the treatment, respectively (P < 0.001). The
      mean prostate volume was decreased from 41.50 +/- 10.85 mL to 30.40 +/- 8.05 mL
      (P < 0.001). The Qmax was increased from 7.87 +/- 2.01 mL/s to 16.19 +/- 1.76
      mL/s (P < 0.001). The mean PSA was 3.12 +/- 0.49 ng/mL and 1.71 +/- 0.39 ng/mL
      before and after treatment, respectively (P < 0.001). The mean PVR was 75.6 +/-
      51.63 mL and 63.50 +/- 36.59 mL before and after treatment, respectively (P =
      0.096). The mean number of nocturia was decreased from 4.1 +/- 0.87 to 2.4 +/-
      0.84 (P < 0.001). The mean IPSS, Prostate volume, PSA and frequency of nocturia
      were decreased significantly. Although mean PVR was decreased but it wasn't
      statistically significant. The mean Qmax was increased significantly. CONCLUSION:
      Intraprostatic injection of Botulinum-A may be an effective and safe treatment
      for symptomatic BPH in selected patients whose medical treatment has faced
      failure and are poor surgical candidates. Transurethral method could be selected
      as a preferable technique of injection.

PMID- 22411421
TI  - The episodic nature of episodic-like memories.
AB  - Studying episodic memory in nonhuman animals has proved difficult because
      definitions in humans require conscious recollection. Here, we assessed humans'
      experience of episodic-like recognition memory tasks that have been used with
      animals. It was found that tasks using contextual information to discriminate
      events could only be accurately performed using recollection, not familiarity.
      However, tasks using temporal information to discriminate events could be
      accurately performed using either recollection or familiarity. The results
      strengthen the position that some episodic-like recognition memory tasks are a
      valid model of episodic memory. However, tasks that rely on temporal information
      may be susceptible to nonepisodic strategies.

PMID- 22411420
TI  - Estimates of the population prevalence of injection drug users among hispanic
      residents of large US metropolitan areas.
AB  - Little information exists on the population prevalence or geographic distribution
      of injection drug users (IDUs) who are Hispanic in the USA. Here, we present
      yearly estimates of IDU population prevalence among Hispanic residents of the 96
      most populated US metropolitan statistical areas (MSAs) for 1992-2002. First,
      yearly estimates of the proportion of IDUs who were Hispanic in each MSA were
      created by combining data on (1) IDUs receiving drug treatment services in
      Substance Abuse and Mental Health Services Administration (SAMHSA)'s Treatment
      Entry Data System, (2) IDUs being tested in the Centers for Disease Control and
      Prevention (CDC) HIV-Counseling and Testing System, and (3) incident AIDS
      diagnoses among IDUs, supplemented by (4) data on IDUs who were living with AIDS.
      Then, the resulting proportions were multiplied by published yearly estimates of
      the number of IDUs of all racial/ethnic groups in each MSA to produce Hispanic
      IDU population estimates. These were divided by Hispanic population data to
      produce population prevalence rates. Time trends were tested using mixed-effects
      regression models. Hispanic IDU prevalence declined significantly on average
      (1992 mean = 192, median = 133; 2002 mean = 144, median = 93; units are per
      10,000 Hispanics aged 15-64). The highest prevalence rates across time tended to
      be in smaller northeastern MSAs. Comparing the last three study years to the
      first three, prevalence decreased in 82% of MSAs and increased in 18%.
      Comparisons with data on drug-related mortality and hepatitis C mortality
      supported the validity of the estimates. Generally, estimates of Hispanic IDU
      population prevalence were higher than published estimates for non-Hispanic White
      residents and lower than published estimates for non-Hispanic Black residents.
      Further analysis indicated that the proportion of IDUs that was Hispanic
      decreased in 52% and increased in 48% of MSAs between 2002 and 2007. The
      estimates resulting from this study can be used to investigate MSA-level social
      and economic factors that may have contributed to variations across MSAs and to
      help guide prevention program planning for Hispanic IDUs within MSAs. Future
      research should attempt to determine to what extent these trends are applicable
      to Hispanic national origin subgroups.

PMID- 22411422
TI  - Mushroom bodies of the honeybee brain show cell population-specific plasticity in
      expression of amine-receptor genes.
AB  - Dopamine and octopamine released in the mushroom bodies of the insect brain play
      a critical role in the formation of aversive and appetitive memories,
      respectively. As recent evidence suggests a complex relationship between the
      effects of these two amines on the output of mushroom body circuits, we compared
      the expression of dopamine- and octopamine-receptor genes in three major
      subpopulations of mushroom body intrinsic neurons (Kenyon cells). Using the brain
      of the honeybee, Apis mellifera, we found that expression of amine-receptor genes
      differs markedly across Kenyon cell subpopulations. We found, in addition, that
      levels of expression of these genes change dramatically during the lifetime of
      the bee and that shifts in expression are cell population-specific. Differential
      expression of amine-receptor genes in mushroom body neurons and the plasticity
      that exists at this level are features largely ignored in current models of
      mushroom body function. However, our results are consistent with the growing body
      of evidence that short- and long-term olfactory memories form in different
      regions of the mushroom bodies of the brain and that there is functional
      compartmentalization of the modulatory inputs to this multifunctional brain
      center.

PMID- 22411423
TI  - Experimental protocols for behavioral imaging: seeing animal models of drug abuse
      in a new light.
AB  - Behavioral neuroimaging is a rapidly evolving discipline that represents a
      marriage between the fields of behavioral neuroscience and preclinical molecular
      imaging. This union highlights the changing role of imaging in translational
      research. Techniques developed for humans are now widely applied in the study of
      animal models of brain disorders such as drug addiction. Small animal or
      preclinical imaging allows us to interrogate core features of addiction from both
      behavioral and biological endpoints. Snapshots of brain activity allow us to
      better understand changes in brain function and behavior associated with initial
      drug exposure, the emergence of drug escalation, and repeated bouts of drug
      withdrawal and relapse. Here we review the development and validation of new
      behavioral imaging paradigms and several clinically relevant radiotracers used to
      capture dynamic molecular events in behaving animals. We will discuss ways in
      which behavioral imaging protocols can be optimized to increase throughput and
      quantitative methods. Finally, we discuss our experience with the practical
      aspects of behavioral neuroimaging, so investigators can utilize effective animal
      models to better understand the addicted brain and behavior.

PMID- 22411424
TI  - Cost per treated patient for etanercept, adalimumab, and infliximab across adult
      indications: a claims analysis.
AB  - INTRODUCTION: This paper aims to estimate the annual cost of etanercept,
      adalimumab, and infliximab per treated patient across adult indications using US
      managed care drug use data. METHODS: Adult patients who used etanercept,
      adalimumab, or infliximab were identified in the Thomson Reuters MarketScan(r)
      Commercial Claims and Encounters Database (Thomson Reuters Healthcare, Ann Arbor,
      MI, USA) between January 1, 2005 and June 30, 2009. The index event was the first
      use of etanercept, adalimumab, or infliximab preceded by a diagnosis for
      rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis.
      Patients were defined as either newly initiating or continuing tumor necrosis
      factor (TNF) blocker treatment based on their use during the 6 months before the
      index event. Annual cost per treated patient was the sum of the etanercept,
      adalimumab, and infliximab medication and administration costs during the 12
      months following the index claim. Annual costs were calculated across all
      patients as well as within each indication group and patient type (new initiator
      or continuing). RESULTS: In total, 21,652 patients met the study criteria
      (etanercept n = 12,065; adalimumab n = 5,685; infliximab n = 3,902); 43% of
      patients were new initiators. Patient characteristics were similar across
      treatment groups in terms of age (mean = 49, SD = 10) and gender (66% female).
      Across indications, the mean annual TNF-blocker cost per treated patient was
      $15,345 for etanercept, $18,046 for adalimumab, and $24,018 for infliximab. In
      new initiators, the TNF-blocker cost per treated patient across indications was
      $14,543 for etanercept, $16,978 for adalimumab, and $21,086 for infliximab; among
      patients continuing therapy, annual costs were $15,836 for etanercept, $19,457
      for adalimumab, and $25,748 for infliximab. CONCLUSION: Patients on etanercept
      had the lowest TNF-blocker cost per treated patient for adult indications when
      applying actual drug use from a US-managed care population. TNF-blocker costs per
      treated patient on adalimumab and infliximab were approximately 18% and 57%
      higher than etanercept, respectively, using real-world drug use data.

PMID- 22411425
TI  - Dipeptidyl peptidase-4 inhibitors in the elderly: more benefits or risks?
AB  - Several studies have shown a high prevalence of type 2 diabetes mellitus (T2DM)
      in the elderly, characterized by a paucity of symptoms, which represents an
      obstacle for an early diagnosis. Frequently, T2DM in the elderly is diagnosed
      when a complication occurs, among which are cognitive disorders and/or affective
      disturbances. Moreover, hypoglycemia is a frequent side effect of therapeutic
      treatment with insulin, sulfonylureas or glinides, while other treatments
      (metformin, acarbose, thiazolidinediones, glucagon-like peptide-1 [GLP-1]
      receptor agonists, and dipeptidyl peptidase-4 [DPP4] inhibitors) are capable of
      reducing hyperglycemia without inducing hypoglycemia. Thus, considering that
      older persons are a very heterogeneous group of individuals, management of T2DM
      in the elderly is challenging but there are no available specific treatment goals
      or treatment algorithms for older diabetic patients. Metformin is the recommended
      first-line therapy in all T2DM patients. When metformin is not sufficient to
      achieve the desired therapeutic targets, a second drug can be added. Available
      options include sulfonylureas, meglitinides, alfa-glucosidase inhibitors,
      pioglitazone, insulin, GLP-1 receptor agonists, and DPP-4 inhibitors. The most
      intriguing therapy for older patients is the one based on the so-called
      incretins, i.e., gastrointestinal hormones that, mainly secreted in the
      postprandial phase, stimulate insulin secretion and inhibit glucagon secretion.
      The two most important human incretins are GLP-1 and glucose-dependent
      insulinotropic peptide (GIP). These hormones potentiate the acute effects of
      glucose on pancreatic alfa and beta cells, thus stimulating insulin secretion,
      and only GLP-1 inhibits glucagon secretion in a glucose-dependent manner (that
      is, only when glucose levels are increased); as a result, they reduce
      hyperglycemia with virtually no hypoglycemic risk. Due to their characteristics,
      DPP-4 inhibitors seem to be particularly interesting as potential agents for the
      treatment of older patients with T2DM.

PMID- 22411426
TI  - A meta-analysis of adherence to antiretroviral therapy and virologic responses in
      HIV-infected children, adolescents, and young adults.
AB  - The relationship between adherence to antiretroviral therapy (ART) and virologic
      outcomes in HIV+ children, adolescents, and young adults has been notably
      understudied, with much of the extant research focused on specific sub
      literatures, such as resource-limited regions, specific clinical outcomes and
      time frames. The authors sought to better characterize the relationship between
      adherence to ART and virologic functioning along various sample and
      methodological factors. The authors conducted a meta-analysis of thirty-seven
      studies and utilized a random effects model to generate weighted mean effect
      sizes. In addition, the authors conducted meta-ANOVAs to examine potential
      factors influencing the relationship between adherence and three categories of
      clinical outcomes, specifically Viral Load (VL) <100, VL < 400, and continuously
      measured VL. The analyses included 5,344 HIV+ children, adolescents, and young
      adults. The relationship between adherence behaviors and virologic outcomes
      varied across different methods of measurement and analysis. The relationship
      between adherence and continuously measured VL was significantly larger than for
      dichotomously-coded VL < 400 at Qb (20.69(1), p < .0005). Caregiver self-report
      indices elicited very small to small magnitude effects across both VL < 100 and
      VL < 400 outcomes and combined informant reporting (youth/adolescent and parent)
      produced significantly larger effects than caregiver report alone with adherence
      and VL < 400 outcomes at Qb (9.28(1), p < .005). More recently published trials
      reported smaller relationships between adherence and categorical clinical
      outcomes, such that year of publication significantly negatively correlated with
      VL < 100 (r = -.71(14), p < .005) and VL < 400 (r = -.43(26), p < .02). The data
      suggest that the magnitude of the relationship between ART adherence and
      virologic outcomes among heterogeneous samples of HIV+ children, adolescents and
      young adults varies across virologic outcomes and may be affected by moderating
      sample and methodological factors. Methodological and research recommendations
      for the interpretation of the current findings as well as for future HIV
      adherence related research are presented.

PMID- 22411427
TI  - Operant, oral alcoholic beer self-administration by C57BL/6J mice: effect of
      BHF177, a positive allosteric modulator of GABA(B) receptors.
AB  - RATIONALE: With its high palatability, near-beer has been successfully used in
      rats as a vehicle to induce ethanol oral self-administration. OBJECTIVES: The
      study aimed to develop an operant model of oral alcoholic beer self
      administration promoting a stable intake of pharmacologically relevant amounts of
      ethanol in free-feeding C57BL/6J mice. It also aimed to assess the model's
      predictive validity by evaluating the influence of baclofen, a GABA(B) agonist,
      and BHF177, a GABA(B) positive allosteric modulator, on alcoholic beer self
      administration. METHODS: Mice were trained to self-administer, under a fixed
      ratio three schedule of reinforcement, 10 MUl of beer containing increasing
      ethanol concentrations (0-18% v/v) in daily 30-min sessions. The effects on motor
      coordination (rotarod), locomotor activity (open field, automated cages) and
      anxiety-like behavior (elevated plus maze, EPM) were examined. Baclofen (1.25-5
      mg/kg, intraperitoneal, i.p.) and BHF177 (3.75-30 mg/kg, i.p.) were used to see
      the effects on 9% alcoholic beer and near-beer self-administration. RESULTS: Near
      beer stably maintained operant oral self-administration in mice. Adding ethanol
      to near-beer reduced the number of active lever presses, while the corresponding
      amount of ethanol self-administration increased (0.8-1.0 g/kg/session). Motor
      impairment was observed when more than 1.3 g/kg/session of ethanol was self
      administered with beer and slight but consistent hyperlocomotion with more than
      0.9-1.0 g/kg/session. BHF177 (15 mg/kg) preferentially reduced 9% alcoholic beer
      self-administration, while the higher dose (30 mg/kg)-like baclofen 5 mg/kg-also
      reduced near-beer self-administration. CONCLUSIONS: The operant model of oral
      alcoholic beer self-administration in C57BL/6J mice should prove useful for
      studying ethanol-reinforced behaviors and to identify candidate compounds for the
      pharmacological management of alcohol addiction.

PMID- 22411429
TI  - Comment on: "Effects of a novel mGlu(2/3) receptor agonist prodrug, LY2140023
      monohydrate, on central monoamine turnover as determined in human and rat
      cerebrospinal fluid" (Lowe S, Dean R, Ackermann B, Jackson K, Natanegara F,
      Anderson S, Eckstein J, Yuen E, Ayan-Oshodi M, Ho M, McKinzie D, Perry K,
      Svensson K, Psychopharmacology, 2012).

PMID- 22411428
TI  - Interactions between VTA orexin and glutamate in cue-induced reinstatement of
      cocaine seeking in rats.
AB  - RATIONALE: Glutamate and orexin/hypocretin systems are involved in Pavlovian cue
      triggered drug seeking. OBJECTIVES: Here, we asked whether orexin and glutamate
      interact within ventral tegmental area (VTA) to promote reinstatement of
      extinguished cocaine seeking in a rat self-administration paradigm.
      METHODS/RESULTS: We first found that bilateral VTA microinjections of the orexin
      1 receptor (OX1R) antagonist SB-334867 (SB) or a cocktail of the AMPA and NMDA
      glutamate receptor antagonists CNQX/AP-5 reduced reinstatement of cocaine seeking
      elicited by cues. In contrast, neither of these microinjections nor systemic SB
      reduced cocaine-primed reinstatement. Additionally, unilateral VTA OX1R blockade
      combined with contralateral VTA glutamate blockade attenuated cue-induced
      reinstatement, indicating that VTA orexin and glutamate are simultaneously
      necessary for cue-induced reinstatement. We further probed the receptor
      specificity of glutamate actions in VTA, finding that CNQX, but not AP-5, dose
      dependently attenuated cue-induced reinstatement, indicating that AMPA but not
      NMDA receptor transmission is required for this type of cocaine seeking. Given
      the necessary roles of both OX1 and AMPA receptors in VTA for cue-induced cocaine
      seeking, we hypothesized that these signaling pathways interact during this
      behavior. We found that PEPA, a positive allosteric modulator of AMPA receptors,
      completely reversed the SB-induced attenuation of reinstatement behavior. Intra
      VTA PEPA alone did not alter cue-induced reinstatement, indicating that
      potentiating AMPA activity with this drug specifically compensates for OX1R
      blockade, rather than simply inducing or enhancing reinstatement itself.
      CONCLUSIONS: These findings show that cue-induced, but not cocaine-primed,
      reinstatement of cocaine seeking is dependent upon orexin and AMPA receptor
      interactions in VTA.

PMID- 22411430
TI  - Swine atrophic rhinitis caused by pasteurella multocida toxin and bordetella
      dermonecrotic toxin.
AB  - Atrophic rhinitis is a widespread and economically important swine disease caused
      by Pasteurella multocida and Bordetella bronchiseptica. The disease is
      characterized by atrophy of the nasal turbinate bones, which results in a
      shortened and deformed snout in severe cases. P. multocida toxin and B.
      bronchiseptica dermonecrotic toxin have been considered to independently or
      cooperatively disturb the osteogenesis of the turbinate bone by inhibiting
      osteoblastic differentiation and/or stimulating bone resorption by osteoclasts.
      Recently, the intracellular targets and molecular actions of both toxins have
      been clarified, enabling speculation on the intracellular signals leading to the
      inhibition of osteogenesis.

PMID- 22411432
TI  - Diabetes: Functional beta cells detected in long-standing T1DM--a new hope for
      intervention?

PMID- 22411431
TI  - Columnar cells necessary for motion responses of wide-field visual interneurons
      in Drosophila.
AB  - Wide-field motion-sensitive neurons in the lobula plate (lobula plate tangential
      cells, LPTCs) of the fly have been studied for decades. However, it has never
      been conclusively shown which cells constitute their major presynaptic elements.
      LPTCs are supposed to be rendered directionally selective by integrating
      excitatory as well as inhibitory input from many local motion detectors. Based on
      their stratification in the different layers of the lobula plate, the columnar
      cells T4 and T5 are likely candidates to provide some of this input. To study
      their role in motion detection, we performed whole-cell recordings from LPTCs in
      Drosophila with T4 and T5 cells blocked using two different genetically encoded
      tools. In these flies, motion responses were abolished, while flicker responses
      largely remained. We thus demonstrate that T4 and T5 cells indeed represent those
      columnar cells that provide directionally selective motion information to LPTCs.
      Contrary to previous assumptions, flicker responses seem to be largely mediated
      by a third, independent pathway. This work thus represents a further step towards
      elucidating the complete motion detection circuitry of the fly.

PMID- 22411433
TI  - Nutrition: Dietary protein lowers blood pressure.

PMID- 22411434
TI  - Diabetes: FFAR1 activation improves glycemia.

PMID- 22411437
TI  - Multifocal intrathoracic inflammatory myofibroblastic tumour in children.
AB  - Pulmonary inflammatory myofibroblastic tumour is the most common benign pulmonary
      tumour in childhood; however it is seldom diagnosed radiologically. We report
      three cases of biopsy-proven inflammatory myofibroblastic tumour that presented
      as large aggressive intrathoracic masses mimicking a malignant process. Two cases
      also had multifocal areas of origin. The possibility of inflammatory
      myofibroblastic tumour should be considered in a child presenting with a large
      aggressive pleuropulmonary mass lesion even with multifocal origin.

PMID- 22411435
TI  - Comparative safety of infliximab and etanercept on the risk of serious
      infections: does the association vary by patient characteristics?
AB  - PURPOSE: Infliximab, a chimeric monoclonal anti-TNFalpha antibody, has been found
      to increase the risk of serious infections compared with the TNF receptor fusion
      protein etanercept in some studies. It is unclear whether the risk varies by
      patient characteristics. We conducted a study to address this question. METHODS:
      We identified members of Kaiser Permanente Northern California who initiated
      infliximab (n = 793) or etanercept (n = 2692) in 1997-2007. Using a Cox model, we
      estimated the propensity-score-adjusted hazard ratio (HR) and 95% confidence
      interval (CI) of serious infections requiring hospitalization or opportunistic
      infections comparing infliximab initiators to etanercept initiators. We tested
      whether the adjusted HR differed by age, sex, race/ethnicity, body mass index,
      and smoking status. RESULTS: The crude incidence rate of serious infections per
      100 person-years was 5.4 (95%CI: 3.8, 7.5) in patients <65 years and 16.0 (95%CI:
      10.4, 23.4) in patients >= 65 years during the first 3 months following treatment
      initiation. Compared with etanercept, the adjusted HR during this period was
      elevated for infliximab in patients <65 years (HR: 3.01; 95%CI: 1.49, 6.07), but
      not in those >= 65 years (HR 0.94; 95%CI: 0.41, 2.13). Findings did not suggest
      that the HR varied by the other patient characteristics examined. CONCLUSIONS: An
      increased risk of serious infections associated with infliximab relative to
      etanercept did not appear to be modified by patients' sex, race/ethnicity, body
      mass index, or smoking status. There was an indication that the increased risk
      might be limited to patients <65 years. Additional studies are warranted to
      verify or refute this finding.

PMID- 22411438
TI  - Radiological analysis of a naturally mummified body.
AB  - A body in an advanced stage of mummification was found in a concrete apartment in
      Japan. Natural complete mummification is very rare in Japan's humid and temperate
      climate. We performed multi-slice computed tomography (MSCT) to obtain
      information on the body prior to autopsy. MSCT clearly illustrated old fractures
      in the right lower leg. Bone resists destruction during body decomposition. If
      antemortem medical records of the deceased are available, MSCT scanning can
      provide information for positive identification. At autopsy, the cervical tissues
      presented as a dried mass, and it was difficult to separately remove the hyoid
      bone and thyroid cartilage. Fractures of the large horn of the hyoid bone and
      superior horn of the thyroid cartilage, which are not observed in all
      strangulation cases, strongly suggest criminal activity. The diagnosis of these
      fractures is of great value. In our case, MSCT revealed that there was no
      fracture in the hyoid bone or ossified area of the thyroid cartilage. Hard
      tissues are usually well preserved in mummies. Although MSCT images have limits
      in mummies because of the severe dryness of soft tissues and organs, they could
      become a useful tool not only for personal identification, but also for the
      identification of neck compression.

PMID- 22411439
TI  - A comparison of sensitized Ln(III) emission using pyridine- and pyrazine-2,6
      dicarboxylates.
AB  - The synthesis, X-ray structure, solution stability, and photophysical properties
      of Eu(III) complexes with pyrazine-2,6-dicarboxylic acid (H(2)PYZ) are reported,
      and compared to structurally analogous complexes with pyridine-2,6-dicarboxylic
      acid (H(2)DPA). The [Eu(PYZ)(3)](3-) complex demonstrates highly efficient metal
      centered Eu(III) luminescence in the solid state (Phi(total) ~ 60.9%). In aqueous
      solution, moderate stability is retained at pH 7.4 (pEu ~ 10.5), although
      hydrolysis of the complex anion becomes competitive below mM concentrations, and
      the observed luminescence intensity from the Eu(III) metal ion is reduced as a
      result. A complete evaluation of the thermodynamic solution stability has allowed
      the observed differences in the solution behaviour luminescence properties of
      these complexes to be rationalized. An analysis of their luminescence behaviour
      in the solid state has also allowed a direct comparison of the sensitisation
      behaviour for these isostructural compounds.

PMID- 22411440
TI  - What did the doctor say? Health literacy and recall of medical instructions.
AB  - BACKGROUND: Limited literacy has repeatedly been linked to problems comprehending
      health information, although the majority of studies to date have focused on
      reading various print health materials. We sought to investigate patients'
      ability to recall spoken medical instructions in the context of a hypothetical
      clinical encounter, and whether limited health literacy would adversely affect
      performance on the task. METHODS: A total of 755 patients aged 55 to 74 were
      recruited from 1 academic internal medicine clinic and 3 federally qualified
      health centers. Participants' health literacy skills and recall of spoken medical
      instructions for 2 standard hypothetical video scenarios [wound care,
      gastroesophageal reflux disease (GERD) diagnosis] were assessed. RESULTS: The
      majority (71.6%) of participants had adequate health literacy skills, and these
      individuals performed significantly better in correctly recalling spoken
      information than those with marginal and low literacy in both scenarios: [wound
      care-mean (SD): low 2.5 (1.3) vs. marginal 3.5 (1.3) vs. adequate 4.6 (1.1);
      P<0.001), GERD: low 4.2(1.7) vs. marginal 5.2 (1.7) vs. adequate 6.5 (1.7);
      P<0.001]. Regardless of literacy level, overall recall of information was poor.
      Few recognized pain (28.5%) or fever (28.2%) as signs of infection. Only 40.5% of
      participants correctly recalled when to take their GERD pills. CONCLUSIONS: Many
      older adults may have difficulty remembering verbal instructions conveyed during
      clinical encounters. We found those with lower health literacy to have poorer
      ability to recall information. Greater provider awareness of the impact of low
      health literacy on the recall of spoken instructions may guide providers to
      communicate more effectively and employ strategies to confirm patient
      understanding.

PMID- 22411441
TI  - Language barriers and understanding of hospital discharge instructions.
AB  - BACKGROUND: Effective communication at hospital discharge is necessary for an
      optimal transition and to avoid adverse events. We investigated the association
      of a language barrier with patient understanding of discharge instructions.
      METHODS: Spanish-speaking, Chinese-speaking, and English-speaking patients
      admitted to 2 urban hospitals between 2005 and 2008, comparing patient
      understanding of follow-up appointment type, and medication category and purpose
      between limited English-proficient (LEP) and English-proficient patients.
      RESULTS: Of the 308 patients, 203 were LEP. Rates of understanding were low
      overall for follow-up appointment type (56%) and the 3 medication outcomes
      (category 48%, purpose 55%, both 41%). In unadjusted analysis, LEP patients were
      less likely than English-proficient patients to know appointment type (50% vs.
      66%; P=0.01), medication category (45% vs. 54%; P=0.05), and medication category
      and purpose combined (38% vs. 47%; P=0.04), but equally likely to know medication
      purpose alone. These results persisted in the adjusted models for medication
      outcomes: LEP patients had lower odds of understanding medication category (odds
      ratio 0.63; 95% confidence interval, 0.42-0.95); and category/purpose (odds ratio
      0.59; 95% confidence interval, 0.39-0.89). CONCLUSIONS: Understanding of
      appointment type and medications after discharge was low, with LEP patients
      demonstrating worse understanding of medications. System interventions to improve
      communication at hospital discharge for all patients, and especially those with
      LEP, are needed.

PMID- 22411442
TI  - Comment on Ballard DW, Price M, Fung V, et al. Validation of an algorithm for
      categorizing the severity of hospital emergency department visits. Med Care.
      2010; 48(1): 58-63.

PMID- 22411443
TI  - A novel synonymous SNP in PITX3 is associated with Parkinson's disease in Chinese
      population.
AB  - BACKGROUND AND PURPOSE: Paired-like homeodomain transcription factor 3 (PITX3) is
      an important transcription factor for differentiation and survival of
      dopaminergic neurons. Recent reports have shown a strong association of
      polymorphisms in the PITX3 gene with Parkinson's disease (PD). Our study was
      designed to verify whether three previous PITX3 SNPs (rs2281983, rs4919621 and
      rs3758549) were associated with PD in the Chinese population. We also investigate
      the association of novel polymorphisms in PITX3 gene with PD. METHODS: All the
      polymorphisms of PITX3 we found in this study were sequenced by PCR products from
      both directions with dye terminator methods using an ABI-3100 sequencer. We
      included 356 sporadic PD patients and 300 healthy elderly people as controls.
      RESULTS: We provide evidence for strong association of a novel polymorphism
      c.219G>A (p = 0.000307) with PD. Our data showed that the substitution of
      c.219G>A in PITX3 Exon 3 was significantly higher in PD compared with control.
      Previous finding suggesting three SNPs (rs2281983, rs4919621 and rs3758549) in
      the PITX3 gene to be associated with PD could not be replicated. CONCLUSIONS: Our
      findings indicate that a novel synonymous SNP in PITX3 gene may contribute to PD
      risk in the Chinese population.

PMID- 22411444
TI  - Three-dimensional domain swapping in the protein structure space.
AB  - Since the proposal of three-dimensional (3D) domain swapping, many 3D domain
      swapped structures have been reported. However, when compared with the vast
      protein structure space, it is still unclear whether 3D domain swapping is a
      general mechanism for protein assembly. Here, we investigated this possibility by
      constructing a dataset consisting of more than 500 domain-swapped structures. The
      domain-swapped structures were mapped into the protein structure space. We found
      that about 10% of protein folds and 5% of protein families contain domain-swapped
      structures. When comparing the domain-swapped structures in a family/superfamily,
      we found that proteins within a family/superfamily can swap in different ways.
      Interface analysis revealed that the hinge loops contributed more than half of
      the open interface in 70% of bona fide domain-swapped dimers, indicating that the
      hinge loops play an important role in stabilizing the domain-swapped
      conformations. Our study supports the suggestion that domain swapping is a
      general property of all proteins and will facilitate further understanding the
      mechanism of 3D domain swapping.

PMID- 22411445
TI  - Detecting open spina bifida at the 11-13-week scan by assessing intracranial
      translucency and the posterior brain region: mid-sagittal or axial plane?

PMID- 22411446
TI  - Standardization of fetal ultrasound biometry measurements: improving the quality
      and consistency of measurements.
AB  - OBJECTIVE: To assess whether a standardization exercise prior to commencing a
      fetal growth study involving multiple sonographers can reduce interobserver
      variation. METHODS: In preparation for an international study assessing fetal
      growth, nine experienced sonographers from eight countries participated in a
      standardization exercise consisting of theoretical and practical sessions. Each
      performed a set of seven standard fetal measurements on pregnant volunteers at 20
      37 weeks' gestation, and these were repeated by the lead sonographer; all
      measurements were taken in a blinded fashion. After this the sonographers had
      hands-on practice and feedback sessions on other volunteers. This process was
      repeated three times. Measurement differences between sonographers and the lead
      sonographer, expressed as a gestational-age-specific Z-score, between the first
      and third scans were compared using the Wilcoxon signed ranks test, and variance
      was assessed using Pitman's test. Interobserver agreement was also assessed using
      the intraclass correlation coefficient (ICC), and all images were scored for
      quality in a blinded fashion. RESULTS: At baseline the level of agreement and
      image scoring were high. A significant reduction in the differences between
      sonographers and the lead sonographer were seen for fetal biometry overall (head
      circumference, abdominal circumference and femur length) between the first and
      third scans (median Z-scores, 0.46 and 0.24; P = 0.005), and a reduction in the
      variance was also observed (P < 0.001). The ICCs for measurement pairs for every
      fetal measurement showed a clear trend of increasing ICC (better agreement) with
      consecutive training scan sessions, although no improvement in image scores was
      seen. CONCLUSION: Even for experienced sonographers, a standardization exercise
      before starting a study of fetal biometry can improve consistency of
      measurements. This could be of relevance for studies assessing fetal growth in
      multicenter sites.

PMID- 22411449
TI  - Assessment of accused juvenile sex offenders in Germany: a comparison of five
      different measures.
AB  - The present study examines the relationship between risk and protective factors
      among young alleged sexual offenders (N = 66) in pre-trial and pre-treatment
      settings. For risk assessment purposes, the Screening Tool for the Assessment of
      Young Sexual Offenders' Risk (STAYSOR), the Structured Assessment of Violence
      Risk in Youth (SAVRY), and the Structured Assessment of Protective Factors for
      violence risk (SAPROF) were used. Psychopathological indicators measured with the
      Basis Raads Onderzoek (BARO) and the German adaption of the Reynolds Adolescent
      Adjustment Screening Inventory (RAASI) were used to examine the relationship
      between the risk assessment scales and instruments measuring risk-relevant
      psychopathological constructs. Risk and protective factors were significantly
      negatively correlated. Psychopathological measures were positively correlated
      with risk factors and negatively with protective factors. Although further
      studies on the predictive validity of the instruments are needed, the results of
      the present explorative pilot study indicate that the use of all five instruments
      may be clinically meaningful for the assessment of young persons who are at risk
      of sexual offending.

PMID- 22411450
TI  - An examination of the thermodynamics of fusion, vaporization, and sublimation of
      (R,S)- and (R)-flurbiprofen by correlation gas chromatography.
AB  - The vaporization, fusion, and sublimation enthalpies of (R,S)- and (R)
      flurbiprofen at T = 298.15 K are reported and compared with literature values
      when available. Correlation gas chromatography experiments were first performed
      to identify appropriate standards that could be used for materials containing a
      single fluorine substituent. Subsequent correlations resulted in a vaporization
      enthalpy for (R,S)-flurbiprofen and (R)-flurbiprofen, DeltaH(vap) (298.15 K), of
      (127.5 +/- 5.5) and (127.4 +/- 4.7) kJ mol, respectively. Fusion enthalpies,
      DeltaH(fus) (387 K), of (28.2 +/- and, DeltaH(fus) (381 K), (22.8 +/- kJ mol(-1)
      were also measured by differential scanning calorimetry for the racemic and
      chiral forms of flurbiprofen. Adjusted to T = 298.15 K and combined with the
      vaporization enthalpy resulted in sublimation enthalpies, DeltaH(sub) (298.15 K),
      of (155.6 +/- 5.8) and (145.1 +/- 5.7) kJ mol(-1) for (R,S)- and (R)
      flurbiprofen, respectively. The fusion enthalpy measured for the racemic form was
      in excellent agreement with the literature value, while the sublimation enthalpy
      varies substantially from previous work. Two weak solid-solid phase transitions
      were also observed for (R)-flurbiprofen at T = 353.9 K (0.30 +/- 0.1) and 363.2 K
      (0.21 +/- 0.03) kJ . mol(-1).

PMID- 22411451
TI  - Epidemiology and immunology of helminth-HIV interactions.
AB  - PURPOSE OF REVIEW: Helminths and HIV-1 use multiple mechanisms to avoid or
      deviate immune responses, and these mechanisms may interact with important
      consequences for the epidemiology of each infection. In this review, we summarize
      recent immunological and epidemiological advances in the understanding of HIV-1
      helminth co-infections. RECENT FINDINGS: Considering the extent of geographical
      overlap of these chronic infections, there has been so far surprisingly limited
      and inconsistent evidence of important interactive effects, either from
      epidemiological studies examining associations between helminth infection
      indicators and HIV disease parameters, or from studies that have dissected the
      immune mechanisms triggered by each pathogen in isolation and investigated their
      interaction. Systematic reviews have found inconsistent evidence for a beneficial
      effect of anthelmintic treatment of helminth-HIV-1 co-infected individuals on
      viral load or CD4 cell counts. It is not certain that co-infection with HIV-1 and
      helminths will always be more detrimental to the host than either single
      infection alone, or that intervening against co-infections will have only
      beneficial effects. SUMMARY: A consensus on the implications of co-infection on
      de-worming and vaccination policies has not yet emerged. Well powered randomized
      trials in HIV-1-infected individuals with defined helminth infections are
      required to determine the benefits of anthelmintic interventions.

PMID- 22411452
TI  - Effects of helminths and Mycobacterium tuberculosis infection on HIV-1:  a
      cellular immunological perspective.
AB  - PURPOSE OF REVIEW: In many regions of the world, a high prevalence of HIV-1,
      helminthic and Mycobacterium tuberculosis (Mtb) infections can be found. Here, we
      summarize the types of immune responses induced and/or modulated by these
      pathogens and the consequences for HIV-1 disease. RECENT FINDINGS: Helminths
      predominantly induce strong T helper (Th) 2 cellular responses which are
      downregulated in chronic disease. The anatomical niche populated by helminths
      plays a key factor in the effect these parasites have on HIV-1 transmission and
      subsequent replication. Gut-associated helminths have been found to increase HIV
      1 transmission via the lesions they provide. In spite of this, the many immune
      modulatory molecules secreted by the parasites may inhibit or slow HIV-1
      infection. In contrast, Mtb is mainly restricted to the lung and the Mtb-specific
      Th cells induced are highly susceptible to HIV-1 infection and replication.
      Antigens from both pathogens have immunomodulatory activity that can skew
      cellular immune responses in specific directions. SUMMARY: The effect of
      helminths and Mtb on modulating immune responses is varied and complex with both
      their location and phenotype potentially influencing HIV-1 disease. These
      pathogens have evolved a complex array of molecules which have the capacity to
      modulate immunity and preserve pathogen survival.

PMID- 22411453
TI  - 'Coinfection-helminthes and tuberculosis'.
AB  - PURPOSE OF REVIEW: Tuberculosis (TB) continues to be a significant problem and a
      major cause of morbidity and mortality in the developing world despite decades of
      intensive efforts to combat the disease. The poverty in these endemic areas is
      associated with an increased incidence of tropical helminthic infections. The
      purpose of this review is to bring to the fore, the urgent need to unravel the
      potential consequences of helminth coinfection to tuberculosis disease
      pathogenesis and transmission. RECENT FINDINGS: There is now strong experimental
      evidence that helminth-induced T helper (Th)2 and T regulatory (Treg) responses
      impinge on host resistance against Mycobacterium tuberculosis (Mtb) infection.
      Several studies show that Th1 response is reduced in helminth coinfected hosts.
      Emerging studies also indicate that helminth-induced alternatively activated
      macrophages contribute to enhanced susceptibility to TB. Despite studies showing
      an association between helminthes and diminished Th1 immunity, maternal
      antihelminthic treatment had no effect on an infant's response to bacille
      Calmette-Guerin vaccination. SUMMARY: Whether helminthes affect tuberculosis (TB)
      disease is still an open question and clinical trials are warranted to determine
      at the population level whether helminthes enhance TB incidence and transmission
      and diminish the protective immune response to vaccines. Consequently, mass
      deworming of infected individuals could contribute toward overall improvement of
      global public health.

PMID- 22411454
TI  - Preventing motor training through nocebo suggestions.
AB  - Although placebos have repeatedly been shown to increase physical performance and
      endurance, much less is known about the effect of their negative counterpart,
      nocebos. Here, we employ negative suggestions and a sham electrical stimulation
      as a nocebo conditioning procedure in healthy subjects performing a leg extension
      exercise to total exhaustion. Using two different protocols, we analyze the
      contribution of expectation alone or the combination of conditioning and
      expectation to the nocebo effect evaluated as the change of work performed and
      rate of perceived exertion. We find that it is possible to negatively modulate
      the physical performance in both cases, and we argue that this effect can
      effectively offset the outcome of training programs.

PMID- 22411455
TI  - On the use of isoperformance curves for profiling and identification of training
      needs.

PMID- 22411458
TI  - Sympathetic ophthalmia in HIV infection. A clinicopathological case report.
AB  - BACKGROUND: The purpose of this study is to report a case of sympathetic
      ophthalmia (SO) in an HIV-infected patient on treatment with highly active
      antiretroviral therapy (HAART) 9 years after a penetrating eye injury. METHODS:
      The study utilized clinical course and histopathological findings. RESULTS:
      Histopathology of the enucleated right eye showed a predominantly lymphocytic
      inflammatory infiltration with some plasma cells and epithelioid granulomata in
      the choroid, suggesting the diagnosis of SO. CONCLUSIONS: SO seems to be driven
      by T lymphocytes, specifically by the CD4 subset of T cells. HIV-infected
      individuals suffer a decline in CD4 T cell numbers, leading to an acquired
      immunodeficiency that could halt the development of the inflammatory reaction
      responsible for SO. The restoration of the CD4 counts by HAART therapy makes HIV
      infected individuals as susceptible to SO as non-infected ones. To the best of
      our knowledge, there are no cases of SO in HIV-infected patients reported in the
      literature.

PMID- 22411457
TI  - Long-term follow-up of patients treated with multiple fluocinolone acetonide
      implants for noninfectious uveitis.
AB  - PURPOSE: To evaluate long-term outcomes in eyes undergoing exchange of
      fluocinolone acetonide intravitreal implants for noninfectious uveitis. METHODS:
      In this retrospective case series, chart review was conducted of all patients
      treated for noninfectious uveitis with fluocinolone acetonide implants. All
      patients were seen at a single center between 2007 and 2010.We studied eight eyes
      of eight patients who received second implants in exchange for previously placed
      implants and received follow-up care after the implant was exchanged. Main
      outcome measures were visual acuity (VA), recurrence of inflammation, need for
      adjunctive systemic anti-inflammatory treatment and adverse events. RESULTS: We
      studied eight eyes of eight patients. Average length of follow-up after the
      second implant was 32.3 months. Of the eight patients, five experienced
      improvement or stabilization of VA when acuity prior to the initial implant was
      compared to acuity on long-term follow-up. After their first implant, five
      patients experienced disease recurrence. Including all eight patients, the
      estimated median time to recurrence was 35.7 months after the first implant. The
      mean time to reimplantation was 42.7 months. After the second implant, three
      patients experienced recurrence. Including all eight patients, the estimated
      median time to recurrence was 30.1 months after the second implant. Adverse
      events included perioperative complications, elevated intraocular pressure (IOP)
      and cataracts. CONCLUSIONS: Exchanging FA intravitreal implants used to treat
      noninfectious uveitis may be useful in preventing vision loss and recurrence of
      inflammation. Development of elevated IOP and cataract is a potentially serious
      complication. The risks and benefits of implant exchange must be carefully
      considered with this intervention.

PMID- 22411459
TI  - Combined anterior and posterior scleritis associated with central retinal vein
      occlusion: a case report.
AB  - PURPOSE: The purpose of this study is to report an uncommon presentation of
      anterior and posterior scleritis with central retinal vein occlusion METHODS: We
      report a 30-year-old female presenting with unilateral anterior and posterior
      scleritis with concurrent central retinal vein occlusion, the subsequent work-up,
      and the management. The patient presented with decreased vision and extraocular
      and intraocular inflammatory signs in the left eye. RESULTS: At presentation, the
      best corrected visual acuity in the right eye (OD) was 20/20 and left eye (OS)
      was perception of light, with inaccurate projection of rays in all quadrants.
      Intraocular pressure was 12 mmHg in both eyes. OS showed mild proptosis with lid
      edema. Ocular movements were free and full in both eyes. The bulbar conjunctiva
      showed nodular anterior scleritis. OS showed mild vitreous haze with an exudative
      detachment at the posterior pole, disc edema with dilated, congested and tortuous
      veins and multiple dot blot hemorrhages, flame-shaped hemorrhages, and soft
      exudates throughout the posterior pole and mid-periphery An ultrasound B scan
      showed a large hypoechoic area in the sub-Tenon's space (T-sign) suggestive of
      periocular fluid collection and thickened sclero-choroidal complex. Orbital
      ultrasound did not show evidence of any orbital mass or any increase in
      extraocular muscle thickness. Fundus fluorescein angiography showed few areas of
      pinpoint hyperfluorescence in the early phase with leakage in the late phase,
      leakage from the optic disc and vascular staining and pooling of dye in areas of
      exudative detachment in the late phases in the left eye. Systemic work-up was
      within normal limits. The patient responded well over the next month with
      systemic and topical steroids showing complete resolution of the scleritis and
      exudative retinal detachment. CONCLUSION: Simultaneous anterior and posterior
      scleritis with concurrent central retinal vein occlusion is a rare entity
      requiring prompt diagnosis and systemic work-up for efficient management.

PMID- 22411460
TI  - Bilateral scleritis and sclerokeratitis associated with IgA nephropathy.
AB  - PURPOSE: The purpose of this study is to report a case of bilateral nodular
      scleritis in a patient with final diagnosis of IgA nephropathy. METHODS: This is
      an observational case report. RESULTS: A male patient, 42 years old, presented
      with a bilateral nodular scleritis and OD sclerokeratitis. He had a previous
      history of acute otitis media and developed posterior renal failure and arterial
      hypertension. Clinical and systemic findings suggest Wegener's granulomatosis. A
      kidney biopsy was performed, and immunoflourescence findings demonstrated
      granular deposits of IgA in a mesangial pattern confirming the diagnosis of IgA
      nephropathy CONCLUSIONS: IgA nephropathy should be a differential diagnosis in
      patients with scleritis and nephropathy.

PMID- 22411461
TI  - The effect of ketorolac on biofilm of Staphylococcus epidermidis isolated from
      post-cataract endophthalmitis.
AB  - PURPOSE: The purpose of this study is to investigate the effect of ketorolac on
      biofilm formation of Staphylococcus epidermidis isolated from patients with post
      cataract endophthalmitis. METHODS: Forty S. epidermidis strains isolated from
      postoperative endophthalmitis were used for this study. Biofilms were grown on
      microtitre plates for 24 h, dyed, and stained with crystal violet. The mean
      optical density (OD) and the OD ratio (ODr = OD of the treated biofilm/OD of the
      untreated biofilm) were used for quantification. The biofilms were incubated with
      13 mM ketorolac and without ketorolac for controls. RESULTS: The biofilm ODs of
      the S. epidermidis isolates untreated and treated with ketorolac were
      significantly different (0.335 +/- 0.06 versus 0.158 +/- 0.03, respectively; mean
      +/- SD; P < 0.001). Ketorolac reduced S. epidermidis biofilm formation by 47.6 %.
      CONCLUSIONS: Ketorolac, at a concentration of 13 mM, significantly reduces the
      formation of biofilm by strains of S. epidermidis that caused endophthalmitis.

PMID- 22411462
TI  - Role of IL28B polymorphism in the development of hepatitis C virus-induced
      hepatocellular carcinoma, graft fibrosis, and posttransplant antiviral therapy.
AB  - BACKGROUND: The development of liver graft disease is partially determined by
      individual genetic background. Interleukin 28B (IL28B) is strongly suspected to
      be involved in susceptibility for hepatitis C virus (HCV) infection,
      inflammation, and antiviral treatment response before and after liver
      transplantation (LT). Currently, the role of IL28B polymorphism (rs12979860) in
      the development of hepatocellular carcinoma (HCC) is unclear, and only limited
      data are available on the course of HCV recurrence. METHODS: One hundred sixty
      seven HCV-positive patients after LT were genotyped for IL28B (C->T; rs12979860).
      Sixty-one patients with histologically confirmed HCC in the explanted liver were
      compared with 106 patients without HCC regarding IL28B genotypes. Among patients
      with HCC, IL28B genotypes were correlated with tumor histology and pretransplant
      alpha-fetoprotein (AFP) levels. Furthermore, the role of IL28B polymorphism was
      evaluated regarding interferon-based treatment success and fibrosis progression
      after LT. RESULTS: The prevalence of HCC in explanted livers was significantly
      higher among patients with TT genotype, suggesting a protective role of the C
      allele in HCC development (P=0.041). Median AFP level was closely to significance
      higher in the presence of T allele (P=0.052). Significant differences in IL28B
      genotype distribution were detected between AFP-negative and AFP-positive HCCs
      (<15 MUg/L vs. >15 MUg/L; P=0.008). Although no impact could be observed
      regarding acute cellular rejection (P=0.940), T allele was significantly
      associated with antiviral therapy failure (P=0.028) and faster development of
      advanced fibrosis (P=0.017) after LT. CONCLUSION: IL28B polymorphism seems to be
      involved in the development of HCV-induced HCC and in the course of HCV
      recurrence after LT. T allele may be regarded as a genetic risk factor for HCV
      related carcinogenesis, posttransplant fibrosis progression, and antiviral
      therapy failure.

PMID- 22411464
TI  - The human microbiome: at the interface of health and disease.
AB  - Interest in the role of the microbiome in human health has burgeoned over the
      past decade with the advent of new technologies for interrogating complex
      microbial communities. The large-scale dynamics of the microbiome can be
      described by many of the tools and observations used in the study of population
      ecology. Deciphering the metagenome and its aggregate genetic information can
      also be used to understand the functional properties of the microbial community.
      Both the microbiome and metagenome probably have important functions in health
      and disease; their exploration is a frontier in human genetics.

PMID- 22411466
TI  - MicroRNAs and their targets: recognition, regulation and an emerging reciprocal
      relationship.
AB  - MicroRNAs (miRNAs) have emerged as key gene regulators in diverse biological
      pathways. These small non-coding RNAs bind to target sequences in mRNAs,
      typically resulting in repressed gene expression. Several methods are now
      available for identifying miRNA target sites, but the mere presence of an miRNA
      binding site is insufficient for predicting target regulation. Regulation of
      targets by miRNAs is subject to various levels of control, and recent
      developments have presented a new twist; targets can reciprocally control the
      level and function of miRNAs. This mutual regulation of miRNAs and target genes
      is challenging our understanding of the gene-regulatory role of miRNAs in vivo
      and has important implications for the use of these RNAs in therapeutic settings.

PMID- 22411467
TI  - Insights into the regulation of protein abundance from proteomic and
      transcriptomic analyses.
AB  - Recent advances in next-generation DNA sequencing and proteomics provide an
      unprecedented ability to survey mRNA and protein abundances. Such proteome-wide
      surveys are illuminating the extent to which different aspects of gene expression
      help to regulate cellular protein abundances. Current data demonstrate a
      substantial role for regulatory processes occurring after mRNA is made - that is,
      post-transcriptional, translational and protein degradation regulation - in
      controlling steady-state protein abundances. Intriguing observations are also
      emerging in relation to cells following perturbation, single-cell studies and the
      apparent evolutionary conservation of protein and mRNA abundances. Here, we
      summarize current understanding of the major factors regulating protein
      expression.

PMID- 22411470
TI  - Gene expression: Transposon terminators.

PMID- 22411471
TI  - The nature of hydrogen bonds in cytidine...H+...cytidine DNA base pairs.

PMID- 22411472
TI  - Escalation strategies for combination therapy Phase I trials.
AB  - Phase I clinical trials aim to identify a maximum tolerated dose (MTD), the
      highest possible dose that does not cause an unacceptable amount of toxicity in
      the patients. In trials of combination therapies, however, many different dose
      combinations may have a similar probability of causing a dose-limiting toxicity,
      and hence, a number of MTDs may exist. Furthermore, escalation strategies in
      combination trials are more complex, with possible escalation/de-escalation of
      either or both drugs. This paper investigates the properties of two existing
      proposed Bayesian adaptive models for combination therapy dose-escalation when a
      number of different escalation strategies are applied. We assess operating
      characteristics through a series of simulation studies and show that strategies
      that only allow 'non-diagonal' moves in the escalation process (that is, both
      drugs cannot increase simultaneously) are inefficient and identify fewer MTDs for
      Phase II comparisons. Such strategies tend to escalate a single agent first while
      keeping the other agent fixed, which can be a severe restriction when exploring
      dose surfaces using a limited sample size. Meanwhile, escalation designs based on
      Bayesian D-optimality allow more varied experimentation around the dose space
      and, consequently, are better at identifying more MTDs. We argue that for Phase I
      combination trials it is sensible to take forward a number of identified MTDs for
      Phase II experimentation so that their efficacy can be directly compared.
      Researchers, therefore, need to carefully consider the escalation strategy and
      model that best allows the identification of these MTDs.

PMID- 22411482
TI  - Recovery from disordered eating: sufferers' and clinicians' perspectives.
AB  - OBJECTIVE: Disagreement exists on how to define recovery from eating disorders.
      Definitions typically include a combination of physical, cognitive, emotional,
      psychological and social factors. However, none provides multidimensional
      recovery models, addressing and comparing sufferers' and clinicians' viewpoints.
      This study investigates those recovery perspectives. METHOD: Two-hundred and
      thirty-eight participants (individuals with eating difficulties and clinicians
      working in the field) completed a checklist, rating the importance of somatic,
      psychological, emotional, social, eating-related and body experience-related
      recovery criteria. RESULTS: Recovery criteria fell into meaningful factors
      (psychological-emotional-social, weight-controlling behaviours, non-life
      threatening and life-threatening features and evaluation of one's own
      appearance). Sufferers and clinicians agreed on the ranking of importance of
      these factors. However, sufferers considered 'psychological-emotional-social' and
      'evaluation of one's own appearance' criteria as more important to recovery than
      clinicians. DISCUSSION: Findings are discussed in relation to existing research,
      together with study limitations and future research. Clinical implications are
      outlined, focusing on the facilitation of recovery.

PMID- 22411483
TI  - Comparison of clonidine and midazolam as anxiolytic premedication before wisdom
      tooth surgery: a randomized, double-blind, crossover pilot study.
AB  - PURPOSE: Anxiolytic and possible side effects of clonidine 150 MUg compared to
      midazolam 7.5 mg for premedication in surgical wisdom tooth extraction were
      evaluated. METHODS: In a prospective, randomized, double-blind crossover trial,
      ten patients undergoing bilateral wisdom tooth surgery received clonidine or
      midazolam orally 1 h before the treatment. Patients receiving midazolam for the
      first surgery received clonidine at the second surgery and vice versa. The
      anxiolytic efficacy was evaluated with a visual analogue scale (VAS) upon
      admission and 30, 50 and 60 min after administration of the medication. Patient
      satisfaction was recorded on a VAS after surgery and 7 days postoperatively.
      RESULTS: As soon as 30 min after administration of midazolam (p < 0.03) and
      clonidine (p < 0.02), an anxiolytic effect was recorded. Both medications did not
      differ in patient satisfaction. CONCLUSION: Oral administration of clonidine 150
      MUg and midazolam 7.5 mg were rated as medications with equal anxiolytic effects
      before wisdom tooth surgery under local anesthesia.

PMID- 22411484
TI  - Nonparametric confidence intervals for the ratio of marginal hazard rates of
      paired survival times.
AB  - Paired survival times with potential censoring are often observed from two
      treatment groups in clinical trials and other types of clinical studies. The
      ratio of marginal hazard rates may be used to quantify the treatment effect in
      these studies. In this paper, a recently proposed nonparametric kernel method is
      used to estimate the marginal hazard rate, and the method of variance estimates
      recovery (MOVER) is used for the construction of the confidence intervals of a
      time-dependent hazard ratio based on the confidence limits of a single marginal
      hazard rate. Two methods are proposed: one uses the delta method and another
      adopts the transformation method to construct confidence limits for the marginal
      hazard rate. Simulations are performed to evaluate the performance of the
      proposed methods. Real data from two clinical trials are analyzed using the
      proposed methods.

PMID- 22411485
TI  - Associations between cancer-related financial stress and strain and psychological
      well-being among individuals living with cancer.
AB  - BACKGROUND: Cancer places a financial and economic burden on individuals, but
      relatively little is known about the consequences. We investigated associations
      between cancer-related financial stress and strain and psychological well-being.
      METHODS: Individuals >6 months post-diagnosis with breast, prostate and lung
      cancer, identified from the National Cancer Registry Ireland, completed a postal
      questionnaire. Financial stress was assessed by the impact of the cancer
      diagnosis on household ability to make ends meet, financial strain by feelings
      about household financial situation since the cancer diagnosis and psychological
      well-being (depression, anxiety and distress) by the Depression Anxiety Stress
      Scales-21. Logistic regression was used to identify associations between
      financial stress and strain and depression, anxiety and distress of (a) any
      severity and (b) severe or worse. RESULTS: The response rate was 54%. Of 654
      respondents, 49% reported increased financial stress and 32% increased financial
      strain due to cancer. Depression, anxiety and distress were present in: 36%, 29%
      and 29%, respectively (any severity); and 14%, 13% and 13%, respectively (severe
      or worse). In adjusted analyses, depression risk was raised threefold in those
      reporting increased cancer-related financial stress (odds ratio (OR) = 2.79,
      95%CI 1.87-4.17) and increased cancer-related financial strain (OR = 3.56, 95%CI
      2.23-5.67). For severe or worse depression, the risk estimates were more
      pronounced (increased stress: OR = 4.36, 95%CI 2.35-8.10; increased strain: OR =
      8.21, 95%CI 3.79-17.77). Similar associations were found for anxiety and
      distress. CONCLUSIONS: Cancer-related financial stress and strain were
      consistently associated with increased risk of adverse psychological outcomes. If
      confirmed, these findings provide further rationale for initiatives to alleviate
      the financial burden of cancer.

PMID- 22411486
TI  - Metal nanofibers with highly tunable electrical and magnetic properties via
      highly loaded water-based electrospinning.
AB  - Nanofibers are synthesized by electrospinning highly loaded water-based precursor
      polymer hybrid solutions followed by thermal treatment to control crystal
      structure. Electrical conductivity and magnetic coercivity, as shown, are tested
      displaying independent magnetic and electrical property control from coercive to
      superparamagnetic and resistive to near-bulk conductivity at room temperature.

PMID- 22411487
TI  - Disparities in the use of minimally invasive surgery for colorectal disease.
AB  - BACKGROUND: Morbidity and mortality rates for major surgical procedures are
      decreased in high-volume hospitals (HVH). Additionally, HVH are often leaders in
      the utilization of novel surgical technology such as minimally invasive surgery
      (MIS). Although HVH often serve diverse patient populations, it is unknown if
      there are disparities in the application of new surgical technologies within
      these hospitals. We sought to determine if ethnic and socioeconomic disparities
      in the use of MIS for colorectal disease exist at HVH. METHODS: Laparoscopic and
      open colectomies performed at HVH were identified using the 2008 Nationwide
      Inpatient Sample database. ICD-9 codes were used to identify MIS colorectal
      resections. Multiple logistic regression including ethnic and socioeconomic
      variables were used to identify independent predictive factors for undergoing
      MIS. RESULTS: A total of 211,862 colorectal resections were performed at HVH in
      2008. Only 16,637 (7.3%) colorectal resections were performed using MIS. When
      evaluating racial and socioeconomic factors, patients within the highest income
      quartile were more likely to undergo MIS than those in the lowest income groups.
      In addition, patients with Medicaid and uninsured patients were significantly
      less likely to undergo MIS compared to patients with private insurance. Lastly,
      race was not a significant predictive factor for undergoing MIS for colorectal
      disease at HVH. CONCLUSION: There are significant socioeconomic disparities in
      the use of MIS for colorectal disease at HVH. Future studies should be aimed at
      identifying access barriers to MIS in the treatment of colorectal disease.

PMID- 22411488
TI  - Serum CA19-9 is a significant predictor among preoperative parameters for early
      recurrence after resection of pancreatic adenocarcinoma.
AB  - OBJECTIVE: To evaluate the preoperative factors predictive of postoperative early
      recurrence in patients with resected pancreatic cancer focusing on the serum CA19
      9 value. METHODS: One hundred fifty-four patients undergoing surgical resection
      for pancreatic cancer were enrolled in this study. Univariate and multivariate
      analyses were performed to determine the predictors of early recurrence which was
      defined as relapse within 6 months after surgery. RESULTS: On ROC curve analysis,
      the cutoff value of CA19-9 was determined to be 100 U/ml. Of 73 patients with
      CA19-9 value >= 100 U/ml, 39 (53 %) had early recurrence. In contrast, only 9 of
      81 patients (11 %) with CA19-9 value < 100 U/ml developed a recurrence at an
      early period (p < 0.001). Multivariate analysis revealed that CA19-9 value >= 100
      U/ml (odds ratio, 11.2) were significant predictors of early recurrence. The
      overall 3- and 5-year survival rates and median survival times were 47.3 %, 40.1
      %, and 31 months in patients with CA19-9 value < 100 U/ml and 21.2 %, 9.4 %, and
      16 months in patients with CA19-9 value >= 100 U/ml (p < 0.001). CONCLUSIONS: A
      preoperative CA19-9 value >= 100 U/ml was a significant predictor of early
      recurrence and a poor prognosis after resection for pancreatic adenocarcinoma.

PMID- 22411489
TI  - Outpatient diverticulitis: mild or myth?
AB  - BACKGROUND: Diverticulitis is considered common in the outpatient population,
      with mild variants of described diagnostic criteria: left lower quadrant pain,
      fever, and leukocytosis. Here, expected criteria utilization among outpatients
      with a possible diagnosis of diverticulitis is assessed. STUDY DESIGN: Primary
      care acute clinic visits in 2008 for diverticulitis (ICD-9 562.11/562.13) or left
      lower quadrant pain (789.04) were identified among patients >= 40 years old.
      Encounters were reviewed through structured manual chart abstraction and
      evaluated for diagnostic accuracy compared to expected criteria. Analysis
      included inter-rater reliability (kappa tests) and descriptive frequencies by
      diagnosis code and diverticulitis rating (chi (2) tests). RESULTS: A total of 376
      acute visits were identified with codes for diverticulitis (n=97) or left lower
      quadrant pain (n=279). High inter-rater reliability was demonstrated for key
      clinical variables (kappa=0.84-1.0). Left lower quadrant pain was reported in
      >75% of patients, while temperature and white blood cell count data were
      frequently unavailable. Lack of these expected criteria resulted in low
      diagnostic accuracy ratings ("No/unlikely"-53.6% diverticulitis, 88.2% left lower
      quadrant pain, p<0.001). CONCLUSIONS: This investigation raises concern for low
      accuracy in the outpatient diagnosis of diverticulitis due to inconsistent use of
      expected criteria, suggesting a smaller population with true diverticulitis than
      previously anticipated, or lack of criteria applicability in this setting.

PMID- 22411490
TI  - Impact of lymphatic vessel invasion on survival in gastric cancer.

PMID- 22411491
TI  - Dimeric aluminum-phosphorus compounds as masked frustrated Lewis pairs for small
      molecule activation.
AB  - Hydroalumination of aryldialkynylphosphines RP(C=C-(t)Bu)(2) (R = Ph, Mes) with
      equimolar quantities of diethylaluminum hydride afforded mixed alkenyl-alkynyl
      cyclic dimers in which the dative aluminum-phosphorus bonds are geminal to the
      exocyclic alkenyl groups. Addition of triethylaluminum to isolated 1 (R = Ph) or
      to the in situ generated species (R = Mes) caused diethylaluminum ethynide
      elimination to yield the arylethylphosphorus dimers 2 and 3. These possess a
      chair-like Al(2)C(2)P(2) heterocycle with intermolecular Al-P interactions. The
      boat conformation (4) was obtained by the reaction of (t)Bu-P(C=C-(t)Bu)(2) with
      di(tert-butyl)aluminum hydride. Despite being dimeric, 2 behaves as a frustrated
      Lewis pair and activates small molecules. The reaction with carbon dioxide gave
      cis/trans isomeric AlPC(2)O heterocycles that differ only by the configuration of
      the exocyclic alkenyl unit. Four isomers resulted from the reaction with phenyl
      isocyanate. This is caused by cis/trans isomerization of the initial C=O adduct
      and subsequent rearrangement to the AlPC(2)N heterocycle, being the C=N adduct.

PMID- 22411492
TI  - Acute kidney injury after composite valve-graft replacement for ascending aorta
      aneurysms.
AB  - Acute kidney injury (AKI) following cardiac surgery is a continuing source of
      morbidity and mortality. Although several studies have attempted to determine its
      etiology and prophylactic measures, limited data exist after thoracic aortic
      surgery. The aim of this study was to evaluate the incidence and predictors of
      AKI in patients undergoing aortic root replacement (ARR) with valve conduit for
      ascending aorta aneurysms. A multi-center observational study of 414 patients
      undergoing ARR with a valve conduit was conducted, focusing on clinical outcome
      and AKI defined by consensus RIFLE (risk, injury, failure, loss of function, end
      stage renal disease) criteria. Mean age was 62.5 years (range: 21-82 years) with
      327 males (79%). Emergent operations were performed in 5% of the cases, while
      concomitant surgical procedures were performed in 24.9%. Postoperative AKI (all
      RIFLE classes) occurred in 69 (16.7%) patients, while eight (1.9%) required
      dialysis. Independent AKI predictors were packed red blood cells (pRBCs) >4 units
      (OR 2.28; 95% CI 1.20-4.30), cardiopulmonary bypass (CPB) time longer than 180
      min (OR, 2.08; 95% CI, 1.16-3.73), and concomitant surgical procedures (OR, 1.85;
      95% CI, 1.04-3.29). The severity of RIFLE class was associated with longer ICU
      stay, hospitalization, and higher hospital mortality (p < 0.001 for each
      variable). AKI after ARR operations with valve conduit for ascending aorta
      aneurysms increases utilization of health resources and is associated with
      adverse events. Concomitant surgical procedures, prolonged CPB-time, and pRBCs >4
      units as independent AKI predictors merit further researches enhancing possible
      preventive strategies.

PMID- 22411493
TI  - Comparison of narrative and expository writing in students with and without
      language-learning disabilities.
AB  - PURPOSE: Students with language-learning disabilities (LLD) demonstrate
      difficulties with written language, especially in the areas of productivity,
      complexity, and grammar. It is not clear how these deficits affect their
      performance on high-stakes tests, such as those required by the No Child Left
      Behind Act (U.S. Department of Education, 2002). This study used writing samples
      to compare how students with and without LLD scored on analytic writing measures
      that are typically used in writing research and on a more holistic measure of
      writing, the six-traits writing rubric (STWR; Education Northwest, 2006), which
      is used in high-stakes writing assessments. METHOD: Fifty-six 4th and 5th graders
      with typical development (TD) or LLD produced 1 narrative and 1 expository
      writing sample. Measures of oral language ability and handwriting accuracy-speed
      were also obtained. The narrative and expository samples were scored using 5-6
      separate analytic measures and 6 separate traits on the STWR. RESULTS: On
      narratives, the TD group scored significantly higher than the LLD group on 5
      analytic measures and all 6 traits. Similarly, for expository, the TD group
      outscored the LLD group on 3 analytic measures and all 6 traits. Results
      demonstrate that the analytic scores of productivity, sentence complexity, and
      lexical diversity were correlated significantly with a higher overall score on
      the STWR for narrative writing samples only. DISCUSSION: Results of this study
      suggest that exclusive use of analytic scores to select treatment goals and
      document writing progress may not translate into increased scores on writing
      rubrics, particularly for expository writing samples.

PMID- 22411494
TI  - Noise hampers children's expressive word learning.
AB  - PURPOSE: To determine the effects of noise and speech style on word learning in
      typically developing school-age children. METHOD: Thirty-one participants ages
      9;0 (years;months) to 10;11 attempted to learn 2 sets of 8 novel words and their
      referents. They heard all of the words 13 times each within meaningful narrative
      discourse. Signal-to-noise ratio (noise vs. quiet) and speech style (plain vs.
      clear) were manipulated such that half of the children heard the new words in
      broadband white noise and half heard them in quiet; within those conditions, each
      child heard one set of words produced in a plain speech style and another set in
      a clear speech style. RESULTS: Children who were trained in quiet learned to
      produce the word forms more accurately than those who were trained in noise.
      Clear speech resulted in more accurate word form productions than plain speech,
      whether the children had learned in noise or quiet. Learning from clear speech in
      noise and plain speech in quiet produced comparable results. CONCLUSION: Noise
      limits expressive vocabulary growth in children, reducing the quality of word
      form representation in the lexicon. Clear speech input can aid expressive
      vocabulary growth in children, even in noisy environments.

PMID- 22411497
TI  - Endoscopic ultrasound-guided drainage of a pelvic abscess via a     J-pouch.

PMID- 22411495
TI  - Vitamin D deficiency among newly resettled refugees in Massachusetts.
AB  - Previous studies have indicated that vitamin D deficiency is widespread among
      immigrants and refugees. This study sought to determine the prevalence of vitamin
      D deficiency among a large and diverse cohort of refugees in Massachusetts to
      assess its significance for routine refugee health screening of refugees. 25
      hydroxyvitamin D levels for 2,610 refugees screened between 2007 and 2009 were
      used to estimate vitamin D status and to examine the relationship between
      deficiency or insufficiency and age, gender, regional origin, and season of
      testing. Among those tested, 78 % were either vitamin D insufficient or
      deficient. Insufficiency or deficiency was most prevalent in refugees from the
      Middle East (89 %) and lowest in those from the Caribbean (59 %). Risk was higher
      among women than among men from some regions, such as the Middle East, but not
      others. For women, the likelihood of deficiency increased with age, while for
      men, the likelihood of deficiency was similar for preschool children and men at
      the height of their working years. The high overall prevalence of vitamin D
      deficiency suggests that empiric supplementation or treatment may be preferred to
      testing until more is known about the long-term epidemiology of vitamin D
      deficiency and its consequences.

PMID- 22411498
TI  - Endoscopic vacuum therapy in the management of anastomotic insufficiency after
      pancreaticoduodenectomy.

PMID- 22411499
TI  - Sequential downgrading of dysplasia in ulcerative colitis using carbon dioxide
      based cryotherapy.

PMID- 22411500
TI  - The folding pathway of glycosomal triosephosphate isomerase: structural insights
      into equilibrium intermediates.
AB  - The guanidine hydrochloride-induced conformational transitions of glycosomal
      triosephosphate isomerase (TIM) were monitored with functional, spectroscopic,
      and hydrodynamic measurements. The equilibrium folding pathway was found to
      include two intermediates (N(2) <->I(2) <->2M<->2U). According to this model, the
      conformational stability parameters of TIM are as follows: DeltaG(I2-N2) = 5.5 +/
      0.6, DeltaG(2M-I2) =19.6 +/- 1.6, and DeltaG(2U-2M) = 14.7 +/- 3.1 kcal mol(-1)
      . The I(2) state is compact (alpha(SR) = 0.8); it is able to bind 8
      anilinonaphthalene-1-sulfonic acid ANS and it is composed of ~45% of alpha-helix
      and tertiary structure content compared with the native enzyme; however, it is
      unable to bind the transition-state analog 2-phosphoglycolate. Conversely, the 2M
      state lacks detectable tertiary contacts, possesses ~10% of the native alpha
      helical content, is significantly expanded (alpha(SR) = 0.2), and has low
      affinity for ANS. We studied the effect of mutating cysteine residues on the
      structure and stability of I(2) and 2M. Three mutants were made: C39A, C126A, and
      C39A/C126A. The replacement of C39, which is located at beta(2) , was found to be
      neutral. The I(2) -C126A state, however, was prone to aggregation and exhibited
      an emission maximum that was 3-nm red-shifted compared with the I(2) -wild type,
      indicating solvent exposure of W90 at beta(4) . Our results suggest that the I(2)
      state comprises the (betaalpha)(1-4) beta(5) module in which the conserved C126
      residue located at beta(5) defines the boundary of the folded segment. We propose
      a folding pathway that highlights the remarkable thermodynamic stability of this
      glycosomal enzyme.

PMID- 22411502
TI  - Examining mental health symptoms in male and female incarcerated juveniles.
AB  - Varying risk factors for both incarceration and mental health diagnoses have been
      identified for female juveniles, highlighting the need for gender-specific
      assessments and treatment protocols. The purpose of this study is to determine
      how the prevalence rates of mental health symptoms differ in male and female
      juvenile offenders. It was hypothesized that the prevalence rates would be
      greater for females than males. This study found significant differences between
      males and females on several clinical scales. These findings are consistent with
      past studies that have identified differences in mental health symptoms between
      genders.

PMID- 22411503
TI  - Theoretical insights into bacterial chemotaxis.
AB  - Research into understanding bacterial chemotactic systems has become a paradigm
      for Systems Biology. Experimental and theoretical researchers have worked hand-in
      hand for over 40 years to understand the intricate behavior driving bacterial
      species, in particular how such small creatures, usually not more than 5 um in
      length, detect and respond to small changes in their extracellular environment.
      In this review we highlight the importance that theoretical modeling has played
      in providing new insight and understanding into bacterial chemotaxis. We begin
      with an overview of the bacterial chemotaxis sensory response, before reviewing
      the role of theoretical modeling in understanding elements of the system on the
      single cell scale and features underpinning multiscale extensions to population
      models.

PMID- 22411504
TI  - Contribution of higher risk genes and European admixture to Crohn's disease in
      African Americans.
AB  - BACKGROUND: African Americans (AAs) are an admixed population of West African
      (WA) and European ancestry (EA). Crohn's disease (CD) susceptibility genes have
      not been established. We therefore evaluated the contribution of European
      admixture and major established risk genes to AA CD. METHODS: Ninety-seven
      admixture informative markers were genotyped for ancestry estimates using
      STRUCTURE. Overall, 354 AA CD cases and 354 ethnicity-matched controls were
      genotyped for total 21 single nucleotide polymorphisms (SNPs) in ATG16L1, NOD2,
      IBD5, IL23R and IRGM by TaqMan or direct sequencing. Association was evaluated by
      logistic regression, adjusted for ancestry. RESULTS: Mean EA was similar among
      the CD cases and controls (20.9% and 20.4%, respectively, P = 0.58). No
      significant admixture differences were observed among 211 to 227 cases stratified
      by phenotypic subclassifications including onset, surgery, site, and behavior. CD
      was associated with NOD2 carrier (6.93% CD, 2.15% Controls, P = 0.007), ATG16L1
      Thr300Ala (36.1% CD, 29.3% Controls, P = 0.003), SLC22A4 and SLC22A5 (IBD5 locus)
      functional SNPs (Leu503Phe [10.5% CD, 7.6% Controls, P = 0.05] and g-207c [41.3%
      CD, 35.7% Controls, P = 0.03], respectively), and IL23R rs2201841 (18.2% CD,
      13.8% Controls, P = 0.03), but not IRGM variants, nor three African ancestral
      NOD2 nonsynonymous variants. IBD5 risk was recessive. An all-minor allele IBD5
      haplotype from EA was associated (P = 0.05), whereas a more common haplotype
      isolating g-207c was not. CONCLUSIONS: Specific functional gene variations
      contribute significantly to AA CD risk. Established NOD2, SLC22A4-A5, and ATG16L1
      variants show increased CD risk, with IBD5 recessive. Although CD is more common
      in whites, European admixture is similar among AA cases and controls.

PMID- 22411506
TI  - A novel locus for restless legs syndrome maps to chromosome 19p in an Irish
      pedigree.
AB  - Restless legs syndrome (RLS) is a common, sleep-related movement disorder. The
      symptoms follow a circadian pattern, worsening in the evening or night, leading
      to sleep disruption and daytime somnolence. Familial forms of RLS have been
      described and usually display an autosomal dominant pattern of inheritance. To
      date, linkage analysis has identified nine RLS loci, but no specific causative
      gene has been reported. Association mapping has highlighted a further four
      genomic areas of interest. We have conducted a genome-wide linkage analysis in an
      Irish autosomal dominant RLS pedigree with 11 affected members. Significant
      linkage was found on chromosome 19p for a series of microsatellite markers, with
      a maximum two-point LOD score of 3.59 at theta = 0.0 for marker D19S878.
      Recombination events, identified by haplotype analysis, define a genetic region
      of 6.57 cM on chromosome 19p13.3, corresponding to an interval of 2.5 Mb. This
      study provides evidence of a novel RLS locus and provides further evidence that
      RLS is a genetically heterogenous disorder.

PMID- 22411505
TI  - Replication study of multiple sclerosis (MS) susceptibility alleles and
      correlation of DNA-variants with disease features in a cohort of Austrian MS
      patients.
AB  - We performed a replication study in 883 Austrian multiple sclerosis (MS) patients
      and 972 control individuals for 25 previously risk-associated loci (39 SNPs). Two
      loci, rs1109670 (DDEF2/MBOAT2, p < 0.02) and rs16914086 (TBC1D2, p < 0.05), are
      replicated here for the first time. Furthermore, we tested all 39 SNPs for
      association with age at disease onset and measures of disease severity. We
      observed a trend for association of rs3135388 (HLA-DRB1*1501, p < 0.01),
      rs7090530 (IL2RA, p < 0.026) and rs1841770 (ZIC1, p < 0.017) with a younger age
      at MS onset and of rs12044852 (CD58, p < 0.035) with shorter time to reach EDSS6.

PMID- 22411507
TI  - Natural variation among Arabidopsis accessions reveals malic acid as a key
      mediator of Nickel (Ni) tolerance.
AB  - Plants have evolved various mechanisms for detoxification that are specific to
      the plant species as well as the metal ion chemical properties. Malic acid, which
      is commonly found in plants, participates in a number of physiological processes
      including metal chelation. Using natural variation among Arabidopsis accessions,
      we investigated the function of malic acid in Nickel (Ni) tolerance and
      detoxification. The Ni-induced production of reactive oxygen species was found to
      be modulated by intracellular malic acid, indicating its crucial role in Ni
      detoxification. Ni tolerance in Arabidopsis may actively involve malic acid
      and/or complexes of Ni and malic acid. Investigation of malic acid content in
      roots among tolerant ecotypes suggested that a complex of Ni and malic acid may
      be involved in translocation of Ni from roots to leaves. The exudation of malic
      acid from roots in response to Ni treatment in either susceptible or tolerant
      plant species was found to be partially dependent on AtALMT1 expression. A lower
      concentration of Ni (10 uM) treatment induced AtALMT1 expression in the Ni
      tolerant Arabidopsis ecotypes. We found that the ecotype Santa Clara (S.C.) not
      only tolerated Ni but also accumulated more Ni in leaves compared to other
      ecotypes. Thus, the ecotype S.C. can be used as a model system to delineate the
      biochemical and genetic basis of Ni tolerance, accumulation, and detoxification
      in plants. The evolution of Ni hyperaccumulators, which are found in serpentine
      soils, is an interesting corollary to the fact that S.C. is also native to
      serpentine soils.

PMID- 22411508
TI  - Changes at the 3'-untranslated region stabilize Rubisco activase transcript
      levels during heat stress in Arabidopsis.
AB  - Inhibition of photosynthesis by heat stress is accompanied by functional
      impairment of Rubisco's chaperone, activase (RCA), resulting in deactivation of
      Rubisco. Since activase is extremely sensitive to thermal denaturation, changes
      in expression of RCA at the transcript or protein level could provide a mechanism
      for acclimation of photosynthesis to prolonged heat stress. Using quantitative
      real-time PCR (qPCR) we show steady-state RCA transcript levels in Arabidopsis
      thaliana are stabilized during prolonged exposure to moderate heat (35   degrees
      C). A survey of RCA transcripts indicates heat stress did not alter the relative
      abundance of transcripts encoding alpha and beta-isoforms of activase that are
      produced by alternative splicing of the pre-mRNA. Instead, mRNA stabilization in
      heat-stressed plants coincided with a significant reduction in the average length
      of activase 3'-untranslated regions, and was associated with enrichment of an
      uncharacterized activase mRNA splice variant, AtRCAbeta2. Transcript-specific
      qPCR revealed AtRCAbeta2 mRNA was more stable than AtRCAalpha and AtRCAbeta mRNA
      in heat-stressed plants. Using an inducible transgenic system, we found that RCA
      transcripts lacking their native 3'-untranslated region were significantly more
      stable than their full-length counterparts in vivo. Using this system, stability
      of the RCA protein was examined over 24 h in vivo, in the absence of RCA
      transcription. At both optimal and elevated temperatures, RCA protein levels
      remained stable in plants lacking RCA mRNA, but increased when RCA mRNA was
      present, particularly in heat-stressed plants. This study reveals a possible
      mechanism, involving post-transcriptional regulation of an important
      photosynthesis regulatory gene, for acclimation of photosynthesis to heat stress.

PMID- 22411509
TI  - Effect of the interaction between employment level and psychosocial work
      environment on insomnia in male Japanese public service workers.
AB  - BACKGROUND: Little is known about the combined risk of socioeconomic status and
      psychosocial environment for insomnia. PURPOSE: The purpose of this study was to
      investigate the combined risk of employment level and psychosocial work
      environment for insomnia in a large Japanese male working population. METHOD: We
      investigated 5,951 male employees aged 34-59 years from two local governments in
      Japan. Data were obtained from a questionnaire distributed in advance of their
      annual health check-up. Employment level was categorized as higher-level non
      manual workers, lower-level non-manual workers, and manual workers. Psychosocial
      work environment was assessed using the Demand-Control Model and the Effort
      Reward Imbalance Model (ERI). Insomnia was assessed using the Athens Insomnia
      Scale. RESULTS: The results showed that 1,382 (23.2 %) participants suffered from
      insomnia. Lower employment level was significantly associated with a higher risk
      of insomnia. Job strain (ratio of job demand to job control), E/R (ratio of job
      effort to job reward), and OC (over commitment) were also significantly
      associated with insomnia. The relative excess risk due to the interaction between
      employment level and psychosocial environment (job strain, E/R, and OC) was 0.09
      (95 % CI -0.57 to 0.76), 2.61 (0.74 to 4.48), and 3.14 (0.82 to 5.45),
      respectively; synergy index = 1.07 (0.66 to 1.74), 1.99 (1.37 to 2.90), and 2.25
      (1.46 to 3.46), respectively. CONCLUSION: We found supra-additive interactions
      between employment level and psychosocial environment, assessed by the ERI (E/R
      and OC). Our findings suggested that lower level workers are more vulnerable to
      an adverse psychosocial environment than those at a higher level.

PMID- 22411510
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: introduction and methodology.
AB  - The Recommendations for Specialized Nutritional Support in Critically-Ill
      patients were drafted by the Metabolism and Nutrition Working Group of the
      Spanish Society of Intensive Care Medicine and Coronary Units (SEMICYUC) in 2005.
      Given the time elapsed since then, these recommendations have been reviewed and
      updated as a Consensus Document in collaboration with the Spanish Society of
      Parenteral and Enteral Nutrition (SENPE). The primary aim of these
      Recommendations was to evaluate the best available scientific evidence for the
      indications of specialized nutritional and metabolic support in critically-ill
      patients. The Recommendations have been formulated by an expert panel with broad
      experience in nutritional and metabolic support in critically-ill patients and
      were drafted between October 2009 and March 2011. The studies analyzed
      encompassed metaanalyses, randomized clinical trials, observational studies,
      systematic reviews and updates relating to critically-ill adults in MEDLINE from
      1966 to 2010, EMBASE reviews from 1991 to 2010 and the Cochrane Database of
      Systematic Reviews up to 2010. The methodological criteria selected were those
      established in the Scottish Intercollegiate Guidelines Network and the Agency for
      Health Care policy and Research, as well as those of the Jadad Quality Scale.
      Adjustment for the level of evidence and grade of recommendation was performed
      following the proposal of the GRADE group (Grading of Recommendations Assessment,
      Development and Evaluation Working Group). Sixteen pathological scenarios were
      selected and each of them was developed by groups of three experts. A feedback
      system was established with the five members of the Editorial Committee and with
      the entire Working Group. All discrepancies were discussed and consensus was
      reached over several meetings, with special emphasis placed on reviewing the
      levels of evidence and grades of recommendation. The Editorial Committee made the
      final adjustments before the document was approved by all the members of the
      Working Group. Finally, the document was submitted to the Scientific Committees
      of the two Societies participating in the Consensus for final approval. The
      present Recommendations aim to serve as a guide for clinicians involved in the
      management and treatment of critically-ill patients and for any specialists
      interested in the nutritional treatment of hospitalized patients.

PMID- 22411511
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: indications, timing and routes of
      nutrient delivery.
AB  - This article discusses basic features of nutritional support in critically-ill
      patients: general indications, the route of administration and the optimal timing
      for the introduction of feeding. Although these features form the bedrock of
      nutritional support, most of the questions related to these issues are lacking
      answers based on the highest grade of evidence. Moreover, prospective randomized
      trials that might elucidate some o f these questions would probably be
      incompatible with good clinical practice. Nevertheless, nutritional support in
      critically-ill patients unable to voluntarily meet their own nutritional
      requirements is currently an unquestionable part of their treatment and care and
      is essential to the successful management of their illness.

PMID- 22411512
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: nutritional assessment.
AB  - Current parameters to assess nutritional status in critically-ill patients are
      useful to evaluate nutritional status prior to admission to the intensive care
      unit. However, these parameters are of little utility once the patient's
      nutritional status has been altered by the acute process and its treatment.
      Changes in water distribution affect anthropometric variables and biochemical
      biomarkers, which in turn are affected by synthesis and degradation processes.
      Increased plasma levels of prealbumin and retinol -proteins with a short half
      life- can indicate adequate response to nutritional support, while reduced levels
      of these proteins indicate further metabolic stress. The parameters used in
      functional assessment, such as those employed to assess muscular or immune
      function, are often altered by drugs or the presence of infection or
      polyneuropathy. However, some parameters can be used to monitor metabolic
      response and refeeding or can aid prognostic evaluation.

PMID- 22411513
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: macronutrient and micronutrient
      requirements.
AB  - Energy requirements are altered in critically-ill patients and are influenced by
      the clinical situation, treatment, and phase of the process. Therefore, the most
      appropriate method to calculate calorie intake is indirect calorimetry. In the
      absence of this technique, fixed calorie intake (between 25 and 35 kcal/kg/day)
      or predictive equations such as the Penn State formula can be used to obtain a
      more accurate evaluation of metabolic rate. Carbohydrate administration should be
      limited to a maximum of 4 g/kg/day and a minimum of 2 g/kg/day. Plasma glycemia
      should be controlled to avoid hyperglycemia. Fat intake should be between 1 and
      1.5 g/kg/day. The recommended protein intake is 1-1.5 g/kg/day but can vary
      according to the patient's clinical status. Particular attention should be paid
      to micronutrient intake. Consensus is lacking on micronutrient requirements. Some
      vitamins (A, B, C, E) are highly important in critically-ill patients, especially
      those undergoing continuous renal replacement techniques, patients with severe
      burns and alcoholics, although the specific requirements in each of these types
      of patient have not yet been established. Energy and protein intake in critically
      ill patients is complex, since both clinical factors and the stage of the process
      must be taken into account. The first step is to calculate each patient's energy
      requirements and then proceed to distribute calorie intake among its three
      components: proteins, carbohydrates and fat. Micronutrient requirements must also
      be considered.

PMID- 22411514
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: acute renal failure.
AB  - Nutritional support in acute renal failure must take into account the patient's
      catabolism and the treatment of the renal failure. Hypermetabolic failure is
      common in these patients, requiring continuous renal replacement therapy or daily
      hemodialysis. In patients with normal catabolism (urea nitrogen below 10 g/day)
      and preserved diuresis, conservative treatment can be attempted. In these
      patients, relatively hypoproteic nutritional support is essential, using proteins
      with high biological value and limiting fluid and electrolyte intake according to
      the patient's individual requirements. Micronutrient intake should be adjusted,
      the only buffering agent used being bicarbonate. Limitations on fluid,
      electrolyte and nitrogen intake no longer apply when extrarenal clearance
      techniques are used but intake of these substances should be modified according
      to the type of clearance. Depending on their hemofiltration flow, continuous
      renal replacement systems require high daily nitrogen intake, which can sometimes
      reach 2.5 g protein/kg. The amount of volume replacement can induce energy
      overload and therefore the use of glucose-free replacement fluids and glucose
      free dialysis or a glucose concentration of 1 g/L, with bicarbonate as a buffer,
      is recommended. Monitoring of electrolyte levels (especially those of phosphorus,
      potassium and magnesium) and of micronutrients is essential and administration of
      these substances should be individually-tailored.

PMID- 22411515
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: liver failure and liver
      transplantation.
AB  - Patients with liver failure have a high prevalence of malnutrition, which is
      related to metabolic abnormalities due to the liver disease, reduced nutrient
      intake and alterations in digestive function, among other factors. In general, in
      patients with liver failure, metabolic and nutritional support should aim to
      provide adequate nutrient intake and, at the same time, to contribute to
      patients' recovery through control or reversal of metabolic alterations. In
      critically-ill patients with liver failure, current knowledge indicates that the
      organ failure is not the main factor to be considered when choosing the
      nutritional regimen. As in other critically-ill patients, the enteral route
      should be used whenever possible. The composition of the nutritional formula
      should be adapted to the patient's metabolic stress. Despite the
      physiopathological basis classically described by some authors who consider amino
      acid imbalance to be a triggering factor and key element in maintaining
      encephalopathy, there are insufficient data to recommend "specific" solutions
      (branched-chain amino acid-enriched with low aromatic amino acids) as part of
      nutritional support in patients with acute liver failure. In patients undergoing
      liver transplantation, nutrient intake should be started early in the
      postoperative period through transpyloric access. Prevention of the hepatic
      alterations associated with nutritional support should also be considered in
      distinct clinical scenarios.

PMID- 22411516
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: severe acute pancreatitis.
AB  - Severe acute pancreatitis (SAP) causes local and systemic complications leading
      to high catabolic, hypermetabolic and hyperdynamic stress states with marked
      morbidity and mortality. In the last decade, nutritional support has become a key
      element in the treatment of SAP. Thus, specialized nutrition is indicated from
      admission, with enteral nutrition being preferred to parenteral nutrition.
      Enteral nutrition should be initiated early using infusion through the jejunum
      beyond the ligament of Treitz to minimize pancreatic stress. There are no
      specific studies that establish the type of diet to be used but experts recommend
      the use of polymeric diets. Parenteral nutrition, without a specific formula, is
      indicated in patients with SAP who are intolerant to enteral nutrition or when
      the clinical signs of pancreatitis are exacerbated or aggravated by enteral
      nutrition. Even so, a minimal level of enteral infusion should be maintained to
      preserve the trophic effect of the intestinal mucosa. In the last few years,
      several studies of the administration of immunomodulatory diets in patients with
      SAP have been carried out to demonstrate their effects on the course of the
      disease. However, there are few clear recommendations on the prognostic benefits
      of pharmaconutrient enriched diets in these patients. There is substantial
      scientific evidence suggesting that the only clear indication for
      pharmaconutrition in patients with SAP is parenteral glutamine administration,
      which is recommended by all clinical guidelines with distinct grades of evidence.

PMID- 22411517
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: respiratory failure.
AB  - Severe acute respiratory failure requiring mechanical ventilation is one of the
      most frequent reasons for admission to the intensive care unit. Among the most
      frequent causes for admission are exacerbation of chronic obstructive pulmonary
      disease and acute respiratory failure with acute lung injury (ALI) or with
      criteria of acute respiratory distress syndrome (ARDS). These patients have a
      high risk of malnutrition due to the underlying disease, their altered catabolism
      and the use of mechanical ventilation. Consequently, nutritional evaluation and
      the use of specialized nutritional support are required. This support should
      alleviate the catabolic effects of the disease, avoid calorie overload and, in
      selected patients, to use omega-3 fatty acid and antioxidant-enriched diets,
      which could improve outcome.

PMID- 22411518
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: gastrointestinal surgery.
AB  - Gastrointestinal surgery and critical illness place tremendous stress on the
      body, resulting in a series of metabolic changes that may lead to severe
      malnutrition, which in turn can increase postsurgical complications and morbidity
      and mortality and prolong the hospital length of stay. In these patients,
      parenteral nutrition is the most widely used form of nutritional support, but
      administration of enteral nutrition early in the postoperative period is
      effective and well tolerated, reducing infectious complications, improving wound
      healing and reducing length of hospital stay. Calorie-protein requirements do not
      differ from those in other critically-ill patients and depend on the patient's
      underlying process and degree of metabolic stress. In patients intolerant to
      enteral nutrition, especially if the intolerance is due to increased gastric
      residual volume, prokinetic agents can be used to optimize calorie intake. When
      proximal sutures are used, tubes allowing early jejunal feeding should be used.
      Pharmaconutrition is indicated in these patients, who benefit from enteral
      administration of arginine, omega 3 and RNA, as well as parenteral glutamine
      supplementation. Parenteral nutrition should be started in patients with absolute
      contraindication for use of the gastrointestinal tract or as complementary
      nutrition if adequate energy intake is not achieved through the enteral route.

PMID- 22411519
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: hyperglycemia and diabetes
      mellitus.
AB  - Hyperglycemia is one of the main metabolic disturbances in critically-ill
      patients and is associated with increased morbidity and mortality. Consequently,
      blood glucose levels must be safely and effectively controlled, that is,
      maintained within a normal range, avoiding hypoglycemia on the one hand and
      elevated glucose concentrations on the other. To accomplish this aim, insulin is
      often required, avoiding protocols designed to achieve tight glycemic control. To
      prevent hyperglycemia and its associated complications, energy intake should be
      adjusted to patients' requirements, avoiding overnutrition and excessive glucose
      intake. Protein intake should be adjusted to the degree of metabolic stress.
      Whenever patients require artificial feeding, the enteral route, if not
      contraindicated, should be used since parenteral nutrition is associated with a
      higher frequency of hyperglycemia and greater insulin requirements. Enteral
      nutrition should be administered early, preferably within the first 24 hours of
      admission to the intensive care unit, after hemodynamic stabilization. Specific
      diets for hyperglycemia, containing low glycemic index carbohydrates and fibre
      and enriched with monounsaturated fatty acids, can achieve good glycemic control
      with lower insulin requirements.

PMID- 22411520
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: oncohematological patient.
AB  - Patients with cancer, irrespective of the stage of their disease, can require
      admission to the intensive care unit as a result of the complications of their
      underlying process or the surgical or pharmacological treatment provided. The
      cancer itself, as well as the critical status that can result from the
      complications of the disease, frequently lead to a high degree of hypermetabolism
      and inadequate energy intake, causing a high incidence of malnutrition in these
      patients. Moreover, cancer causes anomalous use of nutritional substrates and
      therefore the route of administration and proportion and intake of nutrients may
      differ in these patients from those in noncancer patients.

PMID- 22411521
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: obese patient.
AB  - As a response to metabolic stress, obese critically-ill patients have the same
      risk of nutritional deficiency as the non-obese and can develop protein-energy
      malnutrition with accelerated loss of muscle mass. The primary aim of nutritional
      support in these patients should be to minimize loss of lean mass and accurately
      evaluate energy expenditure. However, routinely used formulae can overestimate
      calorie requirements if the patient's actual weight is used. Consequently, the
      use of adjusted or ideal weight is recommended with these formulae, although
      indirect calorimetry is the method of choice. Controversy surrounds the question
      of whether a strict nutritional support criterion, adjusted to the patient's
      requirements, should be applied or whether a certain degree of hyponutrition
      should be allowed. Current evidence suggested that hypocaloric nutrition can
      improve results, partly due to a lower rate of infectious complications and
      better control of hyperglycemia. Therefore, hypocaloric and hyperproteic
      nutrition, whether enteral or parenteral, should be standard practice in the
      nutritional support of critically-ill obese patients when not contraindicated.
      Widely accepted recommendations consist of no more than 60-70% of requirements or
      administration of 11-14 kcal/kg current body weight/day or 22-25 kcal/kg ideal
      weight/day, with 2-2.5 g/kg ideal weight/day of proteins. In a broad sense,
      hypocaloric-hyperprotein regimens can be considered specific to obese critically
      ill patients, although the complications related to comorbidities in these
      patients may require other therapeutic possibilities to be considered, with
      specific nutrients for hyperglycemia, acute respiratory distress syndrome (ARDS)
      and sepsis. However, there are no prospective randomized trials with this type of
      nutrition in this specific population subgroup and the available data are drawn
      from the general population of critically-ill patients. Consequently, caution
      should be exercised when interpreting these data.

PMID- 22411522
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: critically-ill burnt patient.
AB  - The response to severe burns is characterized by hypermetabolism (the most
      hypermetabolic existing model of aggression) and hypercatabolism, with a high
      degree of destruction of the skeletal musculature. Metabolic disorders are most
      evident in the first two weeks after the burn, although they can be prolonged in
      direct relation to the complications that these patients develop. Nutritional
      metabolic support is an essential part of the treatment of these patients and
      should be started early, preferentially through the enteral route, with
      parenteral nutrition as complementary support. Exact calculation of calorie
      protein requirements in these patients is difficult, even when indirect
      calorimetry is used, due to the high loss of proteins and CO2 through the skin.
      Specific pharmaconutrients are indicated, with a high dose of micronutrients. The
      use of drugs or medications with anabolic effects is also sometimes indicated.

PMID- 22411523
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: multiple trauma patient.
AB  - Patients with polytrauma can be viewed as paradigmatic of the critically-ill
      patient. These previously healthy patients undergo a life-threatening aggression
      leading to an organic response that is no different from that in other types of
      patients. The profile of trauma patients has changed and currently corresponds to
      patients who are somewhat older, with a higher body mass index and greater
      comorbidity. Severe injuries lead to intense metabolic stress, posing a risk of
      malnutrition. Therefore, early nutritional support, preferentially through the
      enteral route, with appropriate protein intake and glutamine supplementation,
      provides advantages over other routes and types of nutritional formula. To avoid
      overnutrition, reduced daily calorie intake can be considered in obese patients
      and in those with medullary lesions. However, little information on this topic is
      available in patients with medullary lesions.

PMID- 22411524
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: septic patient.
AB  - Nutritional metabolic management, together with other treatment and support
      measures used, is one of the mainstays of the treatment of septic patients.
      Nutritional support should be started early, after initial life support measures,
      to avoid the consequences of malnutrition, to provide adequate nutritional intake
      and to prevent the development of secondary complications such as superinfection
      or multiorgan failure. As in other critically-ill patients, when the enteral
      route cannot be used to ensure calorie-protein requirements, the association of
      parenteral nutrition has been shown to be safe in this subgroup of patients.
      Studies evaluating the effect of specific pharmaconutrients in septic patients
      are scarce and are insufficient to allow recommendations to be made. To date,
      enteral diets with a mixture of substrates with distinct pharmaconutrient
      properties do not seem to be superior to standard diets in altering the course of
      sepsis, although equally there is no evidence that these diets are harmful. There
      is insufficient evidence to recommend the use of glutamine in septic patients
      receiving parenteral nutrition. However, given the good results and absence of
      glutamine-related adverse effects in the various studies performed in the general
      population of critically-ill patients, these patients could benefit from the use
      of this substance. Routine use of omega-3 fatty acids cannot be recommended until
      further evidence has been gathered, although the use of lipid emulsions with a
      high omega-6 fatty acid content should be avoided. Septic patients should receive
      an adequate supply of essential trace elements and vitamins. Further studies are
      required before the use of high-dose selenium can be recommended.

PMID- 22411525
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: neurocritical patient.
AB  - Neurocritical patients require specialized nutritional support due to their
      intense catabolism and prolonged fasting. The preferred route of nutrient
      administration is the gastrointestinal route, especially the gastric route.
      Alternatives are the transpyloric route or mixed enteral-parenteral nutrition if
      an effective nutritional volume of more than 60% cannot be obtained. Total
      calorie intake ranges from 20-30 kcal/kg/day, depending on the period of the
      clinical course, with protein intake higher than 20% of total calories
      (hyperproteic diet). Nutritional support should be initiated early. The incidence
      of gastrointestinal complications is generally higher to other critically-ill
      patients, the most frequent complication being an increase in gastric residual
      volume. As in other critically-ill patients, glycemia should be closely monitored
      and maintained below 150 mg/dL.

PMID- 22411526
TI  - Guidelines for specialized nutritional and metabolic support in the critically
      ill patient: update. Consensus SEMICYUC-SENPE: cardiac patient.
AB  - Patients with cardiac disease can develop two types of malnutrition: cardiac
      cachexia, which appears in chronic congestive heart failure, and malnutrition due
      to the complications of cardiac surgery or any other type of surgery in patients
      with heart disease. Early enteral nutrition should be attempted if the oral route
      cannot be used. When cardiac function is severely compromised, enteral nutrition
      is feasible, but supplementation with parenteral nutrition is sometimes required.
      Sustained hyperglycemia in the first 24 hours in patients admitted for acute
      coronary syndrome, whether diabetic or not, is a poor prognostic factor for 30
      day mortality. In critically-ill cardiac patients with stable hemodynamic
      failure, nutritional support of 20-25 kcal/kg/day is effective in maintaining
      adequate nutritional status. Protein intake should be 1.2-1.5 g/kg/day. Routine
      polymeric or high protein formulae should be used, according to the patient's
      prior nutritional status, with sodium and volume restriction according to the
      patient's clinical situation. The major energy source for myocytes is glutamine,
      through conversion to glutamate, which also protects the myocardial cell from
      ischemia in critical situations. Administration of 1 g/day of omega-3 (EPA+DHA)
      in the form of fish oil can prevent sudden death in the treatment of acute
      coronary syndrome and can also help to reduce hospital admission for
      cardiovascular events in patients with chronic heart failure.

PMID- 22411527
TI  - Biophysical characterization and stabilization of the recombinant albumin fusion
      protein sEphB4-HSA.
AB  - The use of albumin fusion proteins as therapeutic drug candidates is an
      attractive approach to design novel biopharmaceuticals with increased circulation
      time in vivo. The purpose of this work was to characterize and stabilize the
      fusion protein sEphB4-human serum albumin (HSA), a 120 kDa protein containing the
      extracellular domain of EphB4 and HSA, and to identify stabilizing excipients for
      storage. Comparative biophysical studies combined with empirical phase diagram
      analysis show that both structural integrity and conformational stability of
      sEphB4 and sEphB4-HSA are best maintained above pH 5 and below 50  degrees C,
      with different structural phases observed outside this range. A major physical
      degradation pathway for sEphB4-HSA is formation of soluble aggregates. Excipient
      studies using size-exclusion chromatography (SEC), differential scanning
      calorimetry (DSC), and fluorescence spectroscopy identified disaccharide sugars
      (e.g., sucrose and trehalose) as effective stabilizers against protein
      aggregation, and NaCl as an effective stabilizer for protecting overall
      conformational stability. A combination of biophysical studies with sEphB4-HSA
      and its individual component proteins (sEphB4 and HSA), along with correlation
      analysis of SEC and DSC stability data in the presence of different excipients
      suggest that the aggregation pathway of the albumin fusion protein is primarily
      mediated by the sEphB4 rather than the HSA component.

PMID- 22411528
TI  - Ordering of neuronal apoptosis signaling: a superoxide burst precedes
      mitochondrial cytochrome c release in a growth factor deprivation model.
AB  - Axonal injury to retinal ganglion cells, a defined central neuron, induces a
      burst of intracellular superoxide anion that precedes externalization of membrane
      phosphatidylserine and subsequent apoptotic cell death. Dismutation of superoxide
      prevents the signal and delays loss of these cells, consistent with superoxide
      being necessary for transduction of the axotomy signal. However,
      phosphatidylserine externalization is a relatively late step in apoptosis, and it
      is possible that the superoxide burst is not an early axotomy signal but rather a
      result of cytochrome c release from the mitochondrial inner membrane with
      consequent accumulation of reduced intermediates. Other possibilities are that
      both superoxide generation and cytochrome c release are induced in parallel by
      axotomy, or that cytochrome c release potentiates the effect of the superoxide
      burst. To distinguish these various possibilities, serum-deprived neuronal
      retinal cells were assayed in vitro for superoxide elevation and release of
      cytochrome c from mitochondria, and the distribution of these two markers across
      a large number of cells used to model the temporal ordering of events. Based on
      this model of factor-dependent cell death, superoxide precedes, and possibly
      potentiates, cytochrome c release, and thus the former is likely an early signal
      for certain types of neuronal apoptosis in the central nervous system.

PMID- 22411529
TI  - Involvement of the L-arginine/nitric oxide/cyclic guanosine monophosphate pathway
      in peripheral antinociception induced by N-palmitoyl-ethanolamine in rats.
AB  - N-palmitoyl-ethanolamine (PEA) is an endogenous substance that was first
      identified in lipid tissue extracts. It has been classified as a CB(2) receptor
      agonist. Exogenous PEA has the potential to become a valid treatment for
      neuropathic and inflammatory pain. In spite of the well-demonstrated
      antiinflammatory properties of PEA, its involvement in controlling pain pathways
      remains poorly characterized. The participation of the L-arginine/nitric oxide
      (NO)/cyclic guanosine monophosphate (cGMP) pathway in peripheral antinociception
      has been established by our group to the MU-, kappa- or delta-opioid receptor
      agonists, nonsteroidal analgesics, alpha(2C) -adrenoceptor agonists, and even
      nonpharmacological electroacupuncture. The aim of this study was to verify
      whether the peripheral antinociception effects of PEA involve the activation of
      this pathway. All drugs were locally administered to the right hind paw of male
      Wistar rats. The paw pressure test was used, with hyperalgesia induced by
      intraplantar injection of prostaglandin E(2) . PEA elicited a local peripheral
      antinociceptive effect that was antagonized by the nonselective NO synthase (NOS)
      inhibitor L-NOARG and the selective neuronal NOS (nNOS) inhibitor L-NPA.
      Selective inhibition of endothelial (eNOS) and inducible (iNOS) NOS via L-NIO and
      L-NIL, respectively, was ineffective at blocking the effects of a local PEA
      injection. In addition, the dosage of nitrite in the homogenized paw, as
      determined by colorimetric assay, indicated that exogenous PEA is able to induce
      NO release. The soluble guanylyl cyclase inhibitor ODQ antagonized the PEA
      effect, whereas the cGMP-phosphodiesterase inhibitor zaprinast potentiated the
      antinociceptive effect of low-dose PEA. This study provides evidence that PEA
      activates nNOS, thus initiating the NO/cGMP pathway and inducing peripheral
      antinociceptive effects.

PMID- 22411531
TI  - Combining a hydrogel and an electrochemical biosensor to determine the extent of
      degradation of paper artworks.
AB  - Paper-based artworks are among the most valuable assets for transmission of
      knowledge. Historical paper is composed of different polysaccharides (e.g.
      cellulose), binders, and glues. During aging all of these components undergo
      several degradation processes, as a result of external and intrinsic causes, and
      these can compromise the state of conservation of the document. In this work,
      application of a new biotechnological strategy for paper artefact preservation is
      reported. By making use of innovative and non-invasive materials, for example
      appropriate hydrogels, in combination with selective electrochemical biosensors,
      it is possible to simultaneously verify the degradation condition of the paper
      artwork and then to efficiently clean it, while monitoring the process of removal
      of both pollution and degradation products. In this paper, we focus on specific
      examples in which such techniques have been applied to paper artworks and that
      illustrate the advantages and potential of this biotechnology compared with the
      traditional paper-cleaning methods currently in use.

PMID- 22411533
TI  - Accurate mass screening of pharmaceuticals and fungicides in water by U-HPLC
      Exactive Orbitrap MS.
AB  - The use of pharmaceuticals in livestock production is a potential source of
      surface water, groundwater and soil contamination. Possible impacts of
      antibiotics on the environment include toxicity and the emergence of antibiotic
      resistance. Monitoring programs are required to record the presence of these
      substances in the environment. A rapid, versatile and selective multi-method was
      developed and validated for screening 43 pharmaceutical and fungicides compounds,
      in surface and groundwater, in one single full-scan MS method, using benchtop U
      HPLC-Exactive Orbitrap MS at 50,000 (FWHM) resolution. Detection was based on
      calculated exact masses and on retention time. Sample volume, pH conditions and
      solid-phase extraction (SPE) sample clean-up conditions were optimized. In the
      final method, 74 % of the compounds had recoveries higher than 80 %, 15 % of the
      compounds had recoveries between 60 % and 80 %, and 7 % of the compounds had
      recoveries between 40 % and 50 %. One of the compounds (itraconazole) had a
      recovery lower than 10 % and nystatin was not detected. The level of detection
      was 10 ng L(-1) for 61 % of the compounds, 50 ng L(-1) for 32 % and 100 ng L(-1)
      for 5%. In-house validation, based on EU guidelines, proves that the detection
      capability CCbeta is lower than 10 ng L(-1) (for beta error 5 %) for 37 % of the
      compounds, lower than 50 ng L(-1) for 35 % of the compounds and lower than 100 ng
      L(-1) for 14 % of compounds. This study demonstrates that the ultra-high
      resolution and reliable mass accuracy of Exactive Orbitrap MS permits the
      detection of pharmaceutical residues in a concentration range of 10-100 ng L(-1),
      applying a post target screening approach, in the multi-method conditions.

PMID- 22411534
TI  - Combined drug screening and confirmation by liquid chromatography time-of-flight
      mass spectrometry with reverse database search.
AB  - A method based on in-source collision-induced dissociation (ISCID) liquid
      chromatography time-of-flight mass spectrometry (LC-TOFMS) and reverse target
      database search was developed and evaluated for drug screening and confirmation
      in analytical toxicology context. An established LC-TOFMS screening method, in
      which identification relies solely on protonated molecule accurate mass
      measurement, isotopic pattern fit, and retention time (RT), was completed to
      include 1-3 qualifier ions for each analyte in the database. The qualifier ions
      for 431 compounds were selected from the experimental ISCID spectra, and their
      molecular formulae were assigned by applying SmartFormula3D and MSFragmenter
      software. Three qualifier ions were assigned for 64.5%, two or three for 81.4%,
      one for 14.8%, and none for 3.7% of the compounds studied. Comparison between
      ISCID LC-TOFMS and LC-TOFMS with 25 authentic autopsy urine samples showed an
      improved confidence level with the ISCID method, as isomeric interferences were
      excluded in most cases. However, some false negative (FN) results were obtained
      at low concentration levels close to the reporting criteria. The cut-off
      concentration of the ISCID method was 10-100 ng/mL with 80% of the 49
      representative compounds tested, and the level was approximately two times higher
      than that obtained by LC ion trap MS. The presented method enables simultaneous
      screening and confirmation whenever at least one qualifier ion is available, as
      applying an accurate mass precursor ion and one product ion surpasses the
      standard of four identification points that is required by the current EU
      protocol.

PMID- 22411535
TI  - Pump-probe optical microscopy for imaging nonfluorescent chromophores.
AB  - Many chromophores absorb light intensely but have undetectable fluorescence.
      Hence microscopy techniques other than fluorescence are highly desirable for
      imaging these chromophores inside live cells, tissues, and organisms. The
      recently developed pump-probe optical microscopy techniques provide fluorescence
      free contrast mechanisms by employing several fundamental light-molecule
      interactions including excited state absorption, stimulated emission, ground
      state depletion, and the photothermal effect. By using the pump pulse to excite
      molecules and the subsequent probe pulse to interrogate the created transient
      states on a laser scanning microscope, pump-probe microscopy offers imaging
      capability with high sensitivity and specificity toward nonfluorescent
      chromophores. Single-molecule sensitivity has even been demonstrated. Here we
      review and summarize the underlying principles of this emerging class of
      molecular imaging techniques.

PMID- 22411536
TI  - Quantification of nanoparticles in aqueous food matrices using Particle-Induced X
      ray Emission.
AB  - Nanoparticles (NPs) of SiO(2) (15 nm) or Ag (20 - 40 nm) were dispersed in water,
      coffee and milk at several aqueous dilutions. The NPs dispersions concentrations
      were quantified with an ion beam technique: Particle-Induced X-ray Emission.
      Additional measurements in relation to the state of the NPs dispersions were
      done: particle size distribution by centrifuge liquid sedimentation and the
      extreme surface composition by X-ray photoelectron spectroscopy. The particle
      size distribution of SiO(2) and Ag NPs dispersions in water and Ag NPs in coffee
      remained mostly as primary particles with hydrodynamic diameters close to the
      reported pristine NPs diameter. SiO(2) NPs agglomerated in coffee. In milk, both
      NPs presented an adsorption with milk lipids. Extreme surface composition
      corroborated adsorption in milk and showed that SiO(2) agglomerates adsorb some
      coffee components. A linear tendency in the measurement of the concentration
      dilutions of all dispersions was measured, and a lack of media influence in the
      slope of each curve was found. Limits of detection with the current setup were
      estimated at 0.5 and 0.3 mg/ml for SiO(2) and Ag NPs, respectively.

PMID- 22411537
TI  - Development of novel molecularly imprinted solid-phase microextraction fibers and
      their application for the determination of antibiotic drugs in biological samples
      by SPME-LC/MS(n).
AB  - Novel molecularly imprinted polymer (MIP)-coated fibers for solid-phase
      microextraction (SPME) fibers were prepared by using linezolid as the template
      molecule. The characteristics and application of these fibers were investigated.
      The polypyrrole, polythiophene, and poly(3-methylthiophene) coatings were
      prepared in the electrochemical polymerization way. The molecularly imprinted
      SPME coatings display a high selectivity toward linezolid. Molecularly imprinted
      coatings showed a stable and reproducible response without any influence of
      interferents commonly existing in biological samples. High-performance liquid
      chromatography with spectroscopic UV and mass spectrometry (MS) detectors were
      used for the determination of selected antibiotic drugs (linezolid, daptomycin,
      amoxicillin). The isolation and preconcentration of selected antibiotic drugs
      from new types of biological samples (acellular and protein-free simulated body
      fluid) and human plasma samples were performed. The SPME MIP-coated fibers are
      suitable for the selective extraction of antibiotic drugs in biological samples.

PMID- 22411538
TI  - Validation and application of reporter gene assays for the determination of
      estrogenic and androgenic endocrine disruptor activity in sport supplements.
AB  - Previously developed estrogen and androgen mammalian reporter gene assays (RGAs)
      were assessed for their potential use as a quantitative screening method in the
      detection of estrogenic and androgenic endocrine disruptors (EDs) in sport
      supplements. The validation of both RGAs coupled with dispersive solid phase
      extraction (dSPE) was performed in accordance with European Commission Decision
      EC/2002/6579 for biological screening methods. Decision limits (CCalpha) and
      detection capabilities (CCbeta) were established for both the estrogen and
      androgen RGAs. All samples were compliant with CCalpha and CCbeta in both
      bioassays. Recovery rates were 96 % for 17beta-estradiol and 115 % for
      dihydrotestosterone as obtained in their corresponding RGA. Both estrogens and
      androgens were stable in samples for more than 3 weeks, when stored at -20 
      degrees C. Specificity, good repeatability (coefficients of variation (CV), 12-25
      %), reproducibility and robustness of both bioassays were also observed. Four
      different ED modes of action were determined for estrogens and androgens in 53
      sport supplements, using the validated RGAs. This study revealed that 89 % of the
      investigated sport supplements contained estrogenic EDs and 51 % contained
      androgenic compounds. In conclusion, both bioassays are suitable for sport
      supplement screening of estrogenic and androgenic EDs.

PMID- 22411539
TI  - On-line solid-phase extraction coupled to ultra-performance liquid chromatography
      with tandem mass spectrometry detection for the determination of benzotriazole UV
      stabilizers in coastal marine and wastewater samples.
AB  - Benzotriazoles are a group of UV absorbing compounds considered emerging
      contaminants that are used in different personal care products, and therefore, it
      is of high interest to develop sensitive and fast methods for investigating their
      presence in the environment. In this work, we present the development and
      application of a novel method based on on-line solid-phase extraction coupled to
      ultra-performance liquid chromatography with tandem mass spectrometry detection
      (SPE-UPLC-MS/MS) for the determination of seven benzotriazole UV stabilizers
      (BUVSs) in coastal marine and wastewater samples. This process is compared with a
      conventional off-line SPE procedure followed by UPLC-MS/MS. The parameters
      affecting the performance of the sample preparation and determination processes
      were evaluated. The results indicate that the on-line procedure provides for
      better sensitivity and reproducibility and is faster and easier than the off-line
      procedure. The detection limits and quantification limits achieved were in the
      range of 0.6-4.1 ng?L(-1) and 2.1-14 ng?L(-1) and relative standard deviation
      between 6.2 and 10%. The developed method was applied to coastal marine and
      wastewater samples from Gran Canaria Island (Spain). All of the BUVSs studied
      were detected in the samples from wastewater treatment plants and two were found
      in the seawater samples (UV P in the range of 2.8-4.4 ng?L(-1) and UV 360 between
      3.6 and 5.2 ng?L(-1)).

PMID- 22411540
TI  - Dual labeling of biomolecules using MeCAT and DOTA derivatives: application to
      quantitative proteomics.
AB  - In this study, single and dual labeling of primary amino and thiol groups of
      target peptides is presented as a proof of concept. The proposed method allows
      flexible, independent and sequential labeling of the mentioned residues using
      lanthanides introduced via DOTA-complexes (1,4,7,10-tetraazacyclododecane
      1,4,7,10-tetraacetic acid). The efficiency of the method was optimized using
      cysteine-containing standard peptides and then applied to bovine serum albumin
      (BSA) and human serum albumin (HSA) to demonstrate qualitative and quantitative
      aspects of this strategy. For amino labeling, cysteinyl peptides were immobilized
      on Sepharose-6B resin and labeled with DOTA-NHS ester followed by metallation
      with lanthanides. Thiol labeling was carried out using lanthanide-containing
      metal-coded affinity tags (MeCAT) after elution of peptides from the resin.
      Complete dual labeling of the standard peptides was demonstrated by liquid
      chromatography electrospray ionization mass spectrometry, whereas more than 80%
      of the detected peptides of BSA and HSA were completely dual-labeled. Parallel
      detection by LC coupled to inductively coupled plasma mass spectrometry (ICP-MS)
      delivered reliable quantitative information. Thus, the versatile lanthanide
      choice in both labeling steps allowed estimating primary amino and thiol
      stoichiometries for the studied samples using different lanthanides. On the other
      hand, enhancement of ICP-MS signal was achieved as expected when all positions
      were labeled with the same lanthanide. Finally, linear calibrations of the signal
      for most of the labeled peptides by standard additions of digested BSA showed a
      suitable behaviour for quantitative applications and demonstrated the pre
      concentration capability of the employed resin.

PMID- 22411541
TI  - Cross-cultural adaptation, reliability, internal consistency and validation of
      the Spinal Function Sort (SFS) for French- and German-speaking patients with back
      complaints.
AB  - INTRODUCTION: Functional subjective evaluation through questionnaire is
      fundamental, but not often realized in patients with back complaints, lacking
      validated tools. The Spinal Function Sort (SFS) was only validated in English. We
      aimed to translate, adapt and validate the French (SFS-F) and German (SFS-G)
      versions of the SFS. METHODS: Three hundred and forty-four patients, experiencing
      various back complaints, were recruited in a French (n = 87) and a German
      speaking (n = 257) center. Construct validity was estimated via correlations with
      SF-36 physical and mental scales, pain intensity and hospital anxiety and
      depression scales (HADS). Scale homogeneities were assessed by Cronbach's alpha.
      Test-retest reliability was assessed on 65 additional patients using intraclass
      correlation (IC). RESULTS: For the French and German translations, respectively,
      alpha were 0.98 and 0.98; IC 0.98 (95% CI: [0.97; 1.00]) and 0.94 (0.90; 0.98).
      Correlations with physical functioning were 0.63 (0.48; 0.74) and 0.67 (0.59;
      0.73); with physical summary 0.60 (0.44; 0.72) and 0.52 (0.43; 0.61); with pain 
      0.33 (-0.51; -0.13) and -0.51 (-0.60; -0.42); with mental health -0.08 (-0.29;
      0.14) and 0.25 (0.13; 0.36); with mental summary 0.01 (-0.21; 0.23) and 0.28
      (0.16; 0.39); with depression -0.26 (-0.45; -0.05) and -0.42 (-0.52; -0.32); with
      anxiety -0.17 (-0.37; -0.04) and -0.45 (-0.54; -0.35). CONCLUSIONS: Reliability
      was excellent for both languages. Convergent validity was good with SF-36
      physical scales, moderate with VAS pain. Divergent validity was low with SF-36
      mental scales in both translated versions and with HADS for the SFS-F (moderate
      in SFS-G). Both versions seem to be valid and reliable for evaluating perceived
      functional capacity in patients with back complaints.

PMID- 22411542
TI  - Maskless projection lithography for the fast and flexible generation of grayscale
      protein patterns.
AB  - Protein patterns of different shapes and densities are useful tools for studies
      of cell behavior and to create biomaterials that induce specific cellular
      responses. Up to now the dominant techniques for creating protein patterns are
      mostly based on serial writing processes or require templates such as photomasks
      or elastomer stamps. Only a few of these techniques permit the creation of
      grayscale patterns. Herein, the development of a lithography system using a
      digital mirror device which allows fast patterning of proteins by immobilizing
      fluorescently labeled molecules via photobleaching is reported. Grayscale
      patterns of biotin with pixel sizes in the range of 2.5 MUm are generated within
      10 s of exposure on an area of about 5 mm(2) . This maskless projection
      lithography method permits the rapid and inexpensive generation of protein
      patterns definable by any user-defined grayscale digital image on substrate areas
      in the mm(2)  to cm(2)  range.

PMID- 22411543
TI  - Left ventricular midwall mechanics at 24 weeks' gestation in high-risk
      normotensive pregnant women: relationship to placenta-related complications of
      pregnancy.
AB  - OBJECTIVES: Most studies during pregnancy have assessed maternal left ventricular
      (LV) function by load-dependent indices, assessing only chamber function. The aim
      of this study was to assess afterload-adjusted LV myocardial and chamber systolic
      function at 24 weeks' gestation and 6 months postpartum in high-risk normotensive
      pregnant women. METHODS: A group of 118 high-risk women with bilateral notching
      of the uterine arteries underwent an echocardiographic examination to evaluate
      midwall mechanics (midwall shortening (mFS%) and stress-corrected midwall
      shortening (SCmFS%)) of the LV at 24 weeks' gestation and 6 months postpartum.
      Patients were followed until delivery and pregnancies were classified
      retrospectively as uneventful (uncomplicated outcome) or complicated. A control
      group of 54 low-risk women with uneventful pregnancies without bilateral notching
      was also enrolled. RESULTS: The pregnancy was uneventful in 74 (62.7%) women,
      whereas 44 (37.3%) developed complications. At 24 weeks' gestation, mFS% and
      SCmFS% were greater in the uncomplicated-outcome compared with the complicated
      outcome group (25.9 +/- 4.8 vs 18.8 +/- 5.0%, P < 0.001 and 107.9 +/- 18.4 vs
      77.9 +/- 20.7%, P < 0.001, respectively). At 6 months postpartum, SCmFS% remained
      greater in the uncomplicated-outcome compared with the complicated-outcome group
      (100.4 +/- 21.6 vs 87.8 +/- 19.1, P < 0.05). In the uncomplicated-outcome group,
      SCmFS% was higher during pregnancy than it was postpartum, whereas in the
      complicated-outcome group, it was lower during pregnancy than it was postpartum
      (P < 0.05). CONCLUSIONS: Maternal cardiac midwall mechanics appear to be enhanced
      (SCmFS% increased compared with controls) during pregnancy compared with
      postpartum in high-risk patients with uncomplicated pregnancy, whereas midwall
      mechanics are depressed both during pregnancy and postpartum in patients with
      pregnancy complications.

PMID- 22411544
TI  - Prediction of accrual closure date in multi-center clinical trials with discrete
      time Poisson process models.
AB  - In a phase III multi-center cancer clinical trial or a large public health study,
      sample size is predetermined to achieve desired power, and study participants are
      enrolled from tens or hundreds of participating institutions. As the accrual is
      closing to the target size, the coordinating data center needs to project the
      accrual closure date on the basis of the observed accrual pattern and notify the
      participating sites several weeks in advance. In the past, projections were
      simply based on some crude assessment, and conservative measures were
      incorporated in order to achieve the target accrual size. This approach often
      resulted in excessive accrual size and subsequently unnecessary financial burden
      on the study sponsors. Here we proposed a discrete-time Poisson process-based
      method to estimate the accrual rate at time of projection and subsequently the
      trial closure date. To ensure that target size would be reached with high
      confidence, we also proposed a conservative method for the closure date
      projection. The proposed method was illustrated through the analysis of the
      accrual data of the National Surgical Adjuvant Breast and Bowel Project trial B
      38. The results showed that application of the proposed method could help to save
      considerable amount of expenditure in patient management without compromising the
      accrual goal in multi-center clinical trials.

PMID- 22411545
TI  - Utilisation of intra-operative Doppler in the localisation of pericallosal artery
      during functional hemispherotomies for epilepsy: technical note.
AB  - Functional hemispherotomy is an established technique for treating epilepsy
      secondary to hemispheric pathology. Corpus callosotomy and frontobasal
      disconnection are integral parts of this operation. To perform this, localisation
      of the pericallosal artery through the medial ventricular wall and subpial
      exposure of the A2 and A1 are required. Here, the authors present how intra
      operative Doppler can be useful in helping to localise these arteries in the
      setting of abnormal neuroanatomy and significant brain shift.

PMID- 22411546
TI  - From HMOs to ACOs: the quest for the Holy Grail in U.S. health policy.
AB  - The United States has been singularly unsuccessful at controlling health care
      spending. During the past four decades, American policymakers and analysts have
      embraced an ever changing array of panaceas to control costs, including managed
      care, consumer-directed health care, and most recently, delivery system reform
      and value-based purchasing. Past panaceas have gone through a cycle of excessive
      hope followed by disappointment at their failure to rein in medical care
      spending. We argue that accountable care organizations, medical homes, and
      similar ideas in vogue today could repeat this pattern. We explain why the United
      States persistently pursues health policy fads--despite their poor record--and
      how the promotion of panaceas obscures critical debate about controlling health
      care costs. Americans spend too much time on the quest for the "holy grail"--a
      reform that will decisively curtail spending while simultaneously improving
      quality of care--and too little time learning from the experiences of others.
      Reliable cost control does not, contrary to conventional wisdom, require
      fundamental delivery system reform or an end to fee-for-service payment. It does
      require the U.S. to emulate the lessons of other nations that have been more
      successful at limiting spending through budgeting, system wide fee schedules, and
      concentrated purchasing.

PMID- 22411547
TI  - [Quality assurance in coding expertise of hospital cases in the German DRG
      system. Evaluation of inter-rater reliability in MDK expertise].
AB  - AIM: The purpose of this study was to evaluate differences in the D-DRG results
      of a hospital case by 2 independently coding MKD raters. Calculation of the 2
      inter-rater reliability was performed by examination of the coding of individual
      hospital cases. The reasons for the non-agreement of the expert evaluations and
      suggestions to improve the process are discussed. METHODS: From the expert
      evaluation pool of the MDK-WL a random sample of 0.7% of the 57,375 expertises
      was taken. Distribution equality with the basic total was tested by the chi2 test
      or, respectively, Fisher's exact test. For the total of 402 individual hospital
      cases, the G-DRG case sums of 2 experts of the MDK were determined independently
      and the results checked for each individual case for agreement or non-agreement.
      The corresponding confidence intervals with standard errors were analysed to test
      if certain major diagnosis categories (MDC) were statistically significantly more
      affected by differing expertise results than others. RESULTS: In 280 of the total
      402 tested hospital cases, the 2 MDK raters independently reached the same G-DRG
      results; in 122 cases the G-DRG case sums determined by the 2 raters differed
      (agreement 70%; CI 65.2-74.1). Different DRG results between the 2 experts
      occurred regularly in the entire MDC spectrum. No MDC chapter in which
      significant differences between the 2 raters arose could be identified.
      CONCLUSION: The results of our study demonstrate an almost 70% agreement in the
      evaluation of hospital cost accounts by 2 independently operating MDK. This
      result leaves room for improvement. Optimisation potentials can be recognised on
      the basis of the results. Potential for improvement was established in
      combination with regular further training and the expansion of binding internal
      code recommendations as well as exchange of code-relevant information among
      experts in internal forums. The presented model is in principle suitable for
      cross-border examinations within the MDK system with the advantage that further
      trends could be uncovered by more variety and larger numbers of the randomly
      selected cases.

PMID- 22411548
TI  - [German version of a validated instrument to measure the quality of life in
      patients with hypertension].
AB  - The aim of this study was to prepare according to standardised criteria a German
      version of the validated short instrument for the quality of life in patients
      suffering from hypertension. This instrument is appropriate for clinical trials
      investigating the effectiveness of antihypertensive treatments. But also in the
      daily routine this instrument enables one to identify any impairment of life
      quality due to antihypertensive treatment as early as possible, especially sexual
      dysfunction, and to react appropriately with treatment adaptations.

PMID- 22411549
TI  - Clinical course and pathology in rats (Rattus norvegicus) after experimental
      cowpox virus infection by percutaneous and intranasal application.
AB  - Recently, several cases of human cowpox virus (CPXV) infections were reported in
      France and Germany, which had been acquired through close contact with infected
      pet rats. The animals exhibited respiratory signs or skin lesions and died
      shortly after purchase. After natural infection of white rats with CPXV in the
      USSR in 1978, a peracute pulmonary form, a milder dermal form, and a mixed form
      exhibiting features of both have been described. To the best of the authors'
      knowledge, 3 experimental cowpox virus infection studies using rats have been
      performed to date; however, neither results of histomorphological examinations
      nor immunohistochemical analyses have yet been reported in rats after
      experimental infections. To investigate the impact of the infection route on the
      clinical course, the development of lesions, and tropism, rats were infected
      intradermally, intranasally, or by a combination of both routes. The authors
      found a correlation between clinical manifestation, pathology, and infection
      routes. Intradermal and contact exposure yielded a mild dermal form,
      characterized by the development of vesiculopustular dermatitis. In contrast,
      intranasally infected animals died peracutely, showing severe dyspnea.
      Occasionally, a combination of the dermal and the respiratory form occurred after
      intranasal infection. Immunohistochemically, CPXV antigen was detected in the
      epithelial and mesenchymal cells of the upper respiratory tract and affected skin
      lesions and rarely in mesenchymal cells of lymph nodes. This is the first
      histomorphological and immunohistochemical analysis of CPXV in rats after
      experimental infection.

PMID- 22411550
TI  - Menetrier disease and gastric adenocarcinoma in 3 Cairn terrier littermates.
AB  - Menetrier disease is a rare hypertrophic gastropathy that is characterized by
      hyperplasia of the mucous cells with concurrent loss of chief and parietal cells
      within the gastric glands. There are few reports of this disease in dogs, and
      little is known about the clinical presentation and progression of canine
      Menetrier disease. Three Cairn terrier littermates developed hypertrophic
      gastropathy with histological features of Menetrier disease. One dog remained
      clinically asymptomatic for 2 years after diagnosis. The development of this
      disease in 3 siblings suggests a possible inherited predisposition. All 3 dogs
      also developed gastric neoplasia, which has been reported in human Menetrier
      disease but has not been associated previously with hypertrophic gastropathy in
      domestic species.

PMID- 22411551
TI  - Clinical and histologic features of 26 canine peripheral giant cell granulomas
      (formerly giant cell epulis).
AB  - Clinical and histologic features of 26 cases of canine peripheral giant cell
      granuloma (formerly giant cell epulis) are reported. Two main histologic
      categories were evident: (1) "classic" peripheral giant cell granuloma,
      characterized by variable numbers of multinucleated giant cells (MNGCs) admixed
      with densely cellular mononuclear spindle-shaped cells in variable amounts of
      collagenous matrix, and (2) the "collision" peripheral giant cell granuloma, with
      features of both a peripheral giant cell granuloma and a fibromatous epulis of
      periodontal ligament origin. In the 16 dogs for which the outcome was known, 2
      peripheral giant cell granulomas recurred after excision. No age or sex
      predilection was evident; however, lesions were more common in maxillary than in
      mandibular gingiva. In contrast to cats, peripheral giant cell granulomas in dogs
      behave like fibromatous epulides of periodontal ligament origin and seldom recur
      after excision. Positive staining with TRAP (tartrate-resistant acid phosphatase)
      of the MNGCs and a fraction of the mononuclear cell population is consistent with
      osteoclastic origin.

PMID- 22411552
TI  - Dynamic regulation of sarcoplasmic reticulum Ca(2+)  stores by stromal
      interaction molecule 1 and sarcolipin during muscle differentiation.
AB  - During muscle development, the sarco/endoplasmic reticulum (SR/ER) undergoes
      remodeling to establish a specialized internal Ca(2+) store for muscle
      contraction. We hypothesized that store operated Ca(2+) entry (SOCE) is required
      to fill Ca(2+) stores and is, therefore, critical to creating a mature SR/ER.
      Stromal interaction molecule 1 (STIM1) functions as a sensor of internal Ca(2+)
      store content and an activator of SOCE channels. Myocytes lacking STIM1 display
      reduced SR Ca(2+) content and altered expression of key SR proteins. Sarcolipin
      (SLN), an inhibitor of the SR calcium pump, was markedly increased in the muscle
      of mutant STIM1 mice. SLN opposes the actions of STIM1 by limiting SOCE, reducing
      SR Ca(2+) content and delaying muscle differentiation. During mouse muscle
      development SLN is highly expressed in embryonic muscle, while the expression of
      STIM1 is up-regulated postnatally. These results suggest that SOCE regulates
      SR/ER specialization and that SLN and STIM1 act in opposing fashions to govern
      SOCE during myogenesis.

PMID- 22411553
TI  - Hox transcription factors influence motoneuron identity through the integrated
      actions of both homeodomain and non-homeodomain regions.
AB  - BACKGROUND: Hox transcription factors play a critical role in the specification
      of motoneuron subtypes within the spinal cord. Our previous work showed that two
      orthologous members of this family, Hoxd10 and Hoxd11, exert opposing effects on
      motoneuron development in the lumbosacral (LS) spinal cord of the embryonic
      chick: Hoxd10 promotes the development of lateral motoneuron subtypes that
      project to dorsal limb muscles, while Hoxd11 represses the development of lateral
      subtypes in favor of medial subtypes that innervate ventral limb muscles and
      axial muscles. The striking degree of homology between the DNA-binding
      homeodomains of Hoxd10 and Hoxd11 suggested that non-homeodomain regions mediate
      their divergent effects. In the present study, we investigate the relative
      contributions of homeodomain and non-homeodomain regions of Hoxd10 and Hoxd11 to
      motoneuron specification. RESULTS: Using in ovo electroporation to express
      chimeric and mutant constructs in LS motoneurons, we find that both the
      homeodomain and non-homeodomain regions of Hoxd10 are necessary to specify
      lateral motoneurons. In contrast, non-homeodomain regions of Hoxd11 are
      sufficient to repress lateral motoneuron fates in favor of medial fates.
      CONCLUSIONS: Together, our data demonstrate that even closely related Hox
      orthologues rely on distinct combinations of homeodomain-dependent and 
      independent mechanisms to specify motoneuron identity.

PMID- 22411554
TI  - Neural crest cells pattern the surface cephalic ectoderm during FEZ formation.
AB  - BACKGROUND: Multiple fibroblast growth factor (Fgf) ligands are expressed in the
      forebrain and facial ectoderm, and vascular endothelial growth factor (VEGF) is
      expressed in the facial ectoderm. Both pathways activate the MAP kinase cascade
      and can be suppressed by SU5402. We placed a bead soaked in SU5402 into the brain
      after emigration of neural crest cells was complete. RESULTS: Within 24 hr we
      observed reduced pMEK and pERK staining that persisted for at least 48 hr. This
      was accompanied by significant apoptosis in the face. By day 15, the upper beaks
      were truncated. Molecular changes in the FNP were also apparent. Normally, Shh is
      expressed in the frontonasal ectodermal zone and controls patterned growth of the
      upper jaw. In treated embryos, Shh expression was reduced. Both the structural
      and molecular deficits were mitigated after transplantation of FNP-derived
      mesenchymal cells. CONCLUSIONS: Thus, mesenchymal cells actively participate in
      signaling interactions of the face, and the absence of neural crest cells in
      neurocristopathies may not be merely structural.

PMID- 22411555
TI  - Isl1 and Ldb co-regulators of transcription are essential early determinants of
      mouse limb development.
AB  - BACKGROUND: The developing limb has served as an excellent model for studying
      pattern formation and signal transduction in mammalians. Many of the crucial
      genes that regulate growth and patterning of the limb following limb bud
      formation are now well known. However, details regarding the control of limb
      initiation and early stages of outgrowth remain to be defined. This report is
      focused on genetic events that pave the way for the establishment of a hindlimb
      bud. RESULTS: Fgf10 and Tbx are crucial for early phases of limb bud initiation.
      Here we show that in the absence of Isl1 or of Ldb1/2, there is no hindlimb bud
      development. Fgf10 expression in the bud mesenchyme is dependent on Isl1 and its
      Ldb co-regulators. CONCLUSIONS: Thus, Isl1 and the Ldb co-regulators of
      transcription are essential early determinants of mouse limb development.
      Isl1/Ldb complexes regulate Fgf10 to orchestrate the earliest stages of hindlimb
      formation.

PMID- 22411556
TI  - FoxO1 is required in endothelial but not myocardial cell lineages during
      cardiovascular development.
AB  - BACKGROUND: The forkhead transcription factor FoxO1 is involved in cell cycle
      regulation during cardiovascular development. Systemic loss of FoxO1 results in
      lethality at embryonic day 10.5 with severe cardiovascular defects; however, the
      cell-type-specific requirements for FoxO1 in cardiovascular development are
      unknown. Here we examine the role of FoxO1 using a conditional loss of function
      approach. RESULTS: Loss of FoxO1 in differentiated cardiac myocytes has no
      apparent effect on cardiovascular development. In contrast, endothelial-specific
      FoxO1 deficiency in Tie2Cre;FoxO1(fl/fl) embryos results in lethality at E10.5,
      which recapitulates the FoxO1-null phenotype. Tie2Cre;FoxO1(fl/fl) embryos have
      an intact differentiated endothelium, but display defective remodeling of
      vasculature. Additional effects on heart development include reduced myocardial
      trabeculation, which is likely secondary to the endothelial abnormalities, and
      hypoplasia of endocardial cushions. CONCLUSIONS: The phenotype of
      Tie2Cre;FoxO1(fl/fl) mutant embryos demonstrates that FoxO1 is required
      specifically in endothelial cells to regulate formation of the heart and
      vasculature during development.

PMID- 22411557
TI  - Overlapping expression patterns and redundant roles for AP-2 transcription
      factors in the developing mammalian retina.
AB  - BACKGROUND: We have previously shown that the transcription factor AP-2alpha
      (Tcfap2a) is expressed in postmitotic developing amacrine cells in the mouse
      retina. Although retina-specific deletion of Tcfap2a did not affect
      retinogenesis, two other family members, AP-2beta and AP-2gamma, showed
      expression patterns similar to AP-2alpha. RESULTS: Here we show that, in addition
      to their highly overlapping expression patterns in amacrine cells, AP-2alpha and
      AP-2beta are also co-expressed in developing horizontal cells. AP-2gamma
      expression is restricted to amacrine cells, in a subset that is partially
      distinct from the AP-2alpha/beta-immunopositive population. To address possible
      redundant roles for AP-2alpha and AP-2beta during retinogenesis, Tcfap2a/b
      deficient retinas were examined. These double mutants showed a striking loss of
      horizontal cells and an altered staining pattern in amacrine cells that were not
      detected upon deletion of either family member alone. CONCLUSIONS: These studies
      have uncovered critical roles for AP-2 activity in retinogenesis, delineating the
      overlapping expression patterns of Tcfap2a, Tcfap2b, and Tcfap2c in the neural
      retina, and revealing a redundant requirement for Tcfap2a and Tcfap2b in
      horizontal and amacrine cell development.

PMID- 22411561
TI  - Addressing problems in transplantation research in the United kingdom.
AB  - Transplantation research is complex because of consent being required from
      several individuals, the multiplicity of sites at which donation may occur, its
      unpredictability, and the time constraints. It is also constrained by a tight
      regulatory framework, which seems to be stifling research in the United Kingdom.
      In this article, we recommend that (1) donor consent forms be expanded to include
      consent to research on organs and associated retrieved material,
      contemporaneously and in the future, (2) if a research intervention occurs before
      a recipient is identified, the organ may subsequently be offered on a "take it or
      leave it" basis, (3) if a research intervention occurs after a recipient is
      identified, that recipient has the "right of veto" on the research, (4) patients
      should be able to participate in more than one trial at a time, if clinically
      appropriate, (5) a Research Ethics Committee with specific transplantation
      expertise should be established, (6) the unduly onerous legal obstacles erected
      by the Human Tissue Act (2004) should be removed, and (7) the Organ Donor
      Register should be expanded to include potential donor wishes on research.

PMID- 22411562
TI  - Control of blood pressure in liver transplant recipients.
AB  - BACKGROUND: Increased blood pressure (BP) is common after liver transplantation.
      However, there is scarce information on its control. METHODS: In this
      prospective, cross-sectional, multicenter study, we determined BP according to
      the recommended international standards in 921 liver transplant patients during
      one routine outpatient visit to assess their grade of control of BP. At the time
      of the study, 490 patients had been previously diagnosed with arterial
      hypertension and were receiving antihypertensive treatment, and 431 were not
      previously diagnosed as hypertensive. RESULTS: In the hypertensive group,
      arterial hypertension was uncontrolled (BP >140/90 mm Hg [>130/80 in diabetics])
      in 158 (32%) patients and controlled in 332 (68%) patients. In a multivariate
      analysis, only diabetes was identified as a significant predictor of uncontrolled
      hypertension. Among patients not previously diagnosed as hypertensive, BP was
      increased in 106 (25%) and normal in 325 (75%). On multivariate analysis, the
      only variable independently associated with increased BP in this group was
      metabolic syndrome. CONCLUSION: BP is not adequately controlled in a noticeable
      percentage of liver transplant patients, especially in subjects with diabetes or
      metabolic syndrome.

PMID- 22411563
TI  - Movement kinematics affect action prediction: comparing human to non-human point
      light actions.
AB  - The influence of movement kinematics on the accuracy of predicting the time
      course of another individual's actions was studied. A human point-light shape was
      animated with human movement (natural condition) and with artificial movement
      that was more uniform regarding velocity profiles and trajectories (artificial
      condition). During brief occlusions, the participants predicted the actions in
      order to judge after occlusion whether the actions were continued coherently in
      time or shifted to an earlier or later frame. Error rates and reaction times were
      increased in the artificial compared to the natural condition. The findings
      suggest a perceptual advantage for movement with a human velocity profile,
      corresponding to the notion of a close interaction between observed and executed
      movement. The results are discussed in the framework of the simulation account
      and alternative interpretations are provided on the basis of correlations between
      the velocity profiles of natural and artificial movements with prediction
      performance.

PMID- 22411564
TI  - Effect of ovarian steroids on gene expression related to synapse assembly in
      serotonin neurons of macaques.
AB  - Dendritic spines are the elementary structural units of neural plasticity. In a
      model of hormone replacement therapy (HT), we sought to determine the effect of
      estradiol (E) and progesterone (P) on gene expression related to synapse assembly
      in a laser-captured preparation enriched for serotonin neurons from rhesus
      macaques. Microarray analysis was conducted (n = 2 animals/treatment), and the
      results were confirmed for pivotal genes with qRT-PCR on additional laser
      captured material (n = 3 animals/treatment). Ovariectomized rhesus macaques were
      treated with placebo, E, or E + P via Silastic implants for 1 month. The midbrain
      was obtained, sectioned, and immunostained for tryptophan hydroxylase (TPH). TPH
      positive neurons were laser captured using an arcturus laser dissection
      microscope (Pixel II). RNA from laser-captured serotonin neurons was hybridized
      to Rhesus Affymetrix GeneChips for screening purposes. There was a twofold or
      greater change in the expression of 63 probe sets in the cell adhesion molecule
      (CAM) category, and 31 probe sets in the synapse assembly category were similarly
      altered in E- and E + P-treated animals. qRT-PCR assays showed that E treatment
      induced a significant increase in ephrin receptor A4 (EPHA4) and in integrin A8
      (ITGA8) but not in ephrin receptor B4 (EPHB4) or integrin B8 (ITGB8) expression.
      E also increased expression of cadherin 11 (CDH11), neuroligin 3 (NLGN3),
      neurexin 3 (NRXN3), syndecan 2 (SCD2), and neural cell adhesion molecule (NCAM)
      compared with placebo. Supplemental P treatment suppressed E-induced gene
      expression. In summary, ovarian steroids target gene expression of adhesion
      molecules in serotonin neurons that are important for synapse assembly.

PMID- 22411565
TI  - Ab initio protein structure assembly using continuous structure fragments and
      optimized knowledge-based force field.
AB  - Ab initio protein folding is one of the major unsolved problems in computational
      biology owing to the difficulties in force field design and conformational
      search. We developed a novel program, QUARK, for template-free protein structure
      prediction. Query sequences are first broken into fragments of 1-20 residues
      where multiple fragment structures are retrieved at each position from unrelated
      experimental structures. Full-length structure models are then assembled from
      fragments using replica-exchange Monte Carlo simulations, which are guided by a
      composite knowledge-based force field. A number of novel energy terms and Monte
      Carlo movements are introduced and the particular contributions to enhancing the
      efficiency of both force field and search engine are analyzed in detail. QUARK
      prediction procedure is depicted and tested on the structure modeling of 145
      nonhomologous proteins. Although no global templates are used and all fragments
      from experimental structures with template modeling score >0.5 are excluded,
      QUARK can successfully construct 3D models of correct folds in one-third cases of
      short proteins up to 100 residues. In the ninth community-wide Critical
      Assessment of protein Structure Prediction experiment, QUARK server outperformed
      the second and third best servers by 18 and 47% based on the cumulative Z-score
      of global distance test-total scores in the FM category. Although ab initio
      protein folding remains a significant challenge, these data demonstrate new
      progress toward the solution of the most important problem in the field.

PMID- 22411566
TI  - Tactile skin stimulation increases dopamine release in the nucleus accumbens in
      rats.
AB  - We investigated the effect of mild (non-noxious) tactile stimulation (stroking)
      of skin on dopamine (DA) release in the nucleus accumbens (NAc) of rats. A
      coaxial microdialysis probe was stereotaxically implanted in the NAc and perfused
      with modified Ringer's solution. Dialysate output from consecutive 5-min periods
      was injected into a high-performance liquid chromatograph and DA was measured
      using an electrochemical detector. Bilateral tactile stimulation of the back for
      5 min significantly increased DA release in conscious and anesthetized animals.
      Increased DA release was observed by stimulation of the contralateral, but not
      ipsilateral, back. DA secretion was also increased with stimulation of the
      forelimb, hindlimb, and abdomen. These effects were abolished after lesioning the
      ventral tegmental area (VTA). In contrast, noxious stimulation (pinching) of
      these areas had no effect on DA secretion. In conclusion, innocuous mechanical
      stimulation of the skin increases DA release in the contralateral NAc via the
      VTA.

PMID- 22411567
TI  - Electrospray-differential mobility analysis as an orthogonal tool to size
      exclusion chromatography for characterization of protein aggregates.
AB  - The biopharmaceutical industry characterizes and quantifies aggregation of
      protein therapeutics using multiple analytical techniques to cross-validate
      results. Here, we demonstrate the use of electrospray-differential mobility
      analysis (ES-DMA), a gas-phase and atmospheric pressure ion-mobility method for
      characterizing protein aggregates. Two immunoglobulin Gs are systematically heat
      treated to induce aggregation and characterized using size-exclusion
      chromatography (SEC) and ES-DMA. Although ES-DMA is a gas-phase characterization
      method, we find that aggregation kinetic rate constants determined by ES-DMA is
      in good agreement with those determined by SEC. ES-DMA appears to have a higher
      resolution and lower limit of detection as compared with SEC. Thus, ES-DMA can
      potentially become an important orthogonal tool for characterization of nascent
      protein aggregates in the biopharmaceutical industry.

PMID- 22411569
TI  - One thousand consecutive mini-gastric bypass: short- and long-term outcome.
AB  - There is growing evidence that mini-gastric bypass (MGB) is a safe and effective
      procedure. Operative outcome and long-term follow-up of a consecutive cohort of
      patients who underwent MGB are reported. The data on 1,000 patients who underwent
      MGB from November 2005 to January 2011 at an academic institution were reviewed.
      Mean age was 33.15 +/- 10.17 years (range, 14-72), preoperative BMI was 42.5 +/-
      6.3 kg/m(2) (range, 26-75), mean preoperative weight was 121.6 +/- 23.8 kg
      (range, 71-240), and 663 were women. Operative time and length of stay for
      primary vs. revisional MGB were 89 +/- 12.8 min vs. 144 +/- 15 min (p < 0.01) and
      l.85 +/- 0.8 day vs. 2.35 +/- 1.89 day (p < 0.01). No deaths occurred within 30
      days of surgery. Short-term complications occurred in 2.7% for primary vs. 11.6%
      for revisionnal MGB (p < 0.01). Five (0.5%) patients presented with leakage from
      the gastric tube but none had anastomotic leakage. Four (0.4%) patients, all with
      revisional MGB, presented with severe bile reflux and were cured by stapling the
      afferent loop and by a latero-lateral jejunojejunostomy. Excessive weight loss
      occurred in four patients; two were reversed and two were converted to sleeve
      gastrectomy. Maximal percent excess weight loss (EWL) of 72.5% occurred at 18
      months. Weight regain subsequently occurred with a mean variation of -3.9% EWL at
      60 months. The 50% EWL was achieved for 95% of patients at 18 months and for
      89.8% at 60 months. MGB is an effective, relatively low-risk, and low-failure
      bariatric procedure. In addition, it can be easily revised, converted, or
      reversed.

PMID- 22411568
TI  - Excessive weight loss after sleeve gastrectomy: a systematic review.
AB  - BACKGROUND: The clinical significance of sleeve gastrectomy (SG) as a primary
      bariatric intervention is still under debate. This article aims to systematically
      analyze excessive weight loss (EWL) in patients after SG. METHODS: A systematic
      literature search on SG from the period January 2003 to December 2010 was
      performed. Data described from systematic reviews dealing with gastric bypass
      procedures was used as comparator. RESULTS: The final study included 123 papers
      describing 12,129 patients. Most of the papers describe EWL at 12 months (43.9%
      of all papers). For SG, the maximum EWL occurred 24 and 36 months postoperatively
      with a mean EWL of 64.3% (minimum 46.1%, maximum 75.0%) and 66.0% (minimum 60.0%,
      maximum 77.5%), respectively. At 12 months, the mean EWL in patients receiving SG
      was significantly lower when compared to patients who underwent gastric bypass
      (SG 56.1%, gastric bypass 68.3%; p < 0.01, two-sided Wilcoxon test). Although
      patients with gastric bypass still had higher EWL rates at 24 months compared to
      patients after SG, these differences were not significant (SG 61.3%, gastric
      bypass 69.6%; p = 0.09, two-sided Wilcoxon rank-sum test). Reoperations after SG
      are necessary in 6.8% (range 0.7-25%) of cases with patients receiving SG as a
      stand alone procedure and in 9.6-28.5% of cases with patients undergoing SG as a
      planned first stage procedure. CONCLUSIONS: SG is an effective bariatric
      procedure with a lasting effect on EWL. Compared with gastric bypasses, there is
      no difference in EWL at the time point of 24 months.

PMID- 22411570
TI  - Achalasia-like disorder after laparoscopic adjustable gastric banding: a
      reversible side effect?
AB  - Literature data concerning the effect of laparoscopic adjustable gastric banding
      (LAGB) on esophageal motility are conflicting. Achalasia-like disorder involving
      the absence of esophageal peristalsis and impaired esophago-gastric junction
      (EGJ) is probably under-estimated and can result in failure and band removal. The
      aim of our study was to focus on cases of achalasia-like disorder and study its
      evolution after band deflating or removal. LAGB patients with food intolerance
      and whose esophageal manometry confirmed dysmotility were selected from our
      database. Achalasia-like disorder was defined as the absence of esophageal
      peristalsis (< 20% contraction waves) with impairment of EGJ relaxation.
      Manometric control was performed after removal or band deflating; functional
      results were assessed. Eleven patients among 20 (55%) with esophageal motility
      disorders (EMD) fitted the manometric criteria of achalasia-like disorder with a
      mean EGJ resting pressure of 32.1 cmH(2)O and a EGJ relaxation pressure of 24.2.
      Nine patients out of 11 underwent band removal which resulted in the resolution
      of their symptoms. The other two underwent band deflation. Manometric control
      after band removal showed both a decrease in resting and relaxation EGJ pressures
      (mean of 9.5 and 6.5 cmH(2)O) and a recovery of wave contractions in 87.5% of
      cases. Four patients underwent revision surgery due to weight regain with a
      successful outcome. Achalasia-like disorder is a manometric diagnosis and
      accounts for a significant part of symptomatic EMD after LAGB. It often results
      in band removal, allowing some reversibility of the disorders.

PMID- 22411571
TI  - Validation of the Greek translation of the obesity-specific Moorehead-Ardelt
      Quality-of-Life Questionnaire II.
AB  - Morbid obesity adversely affects quality of life. The assessment of health
      related quality of life (HRQoL) needs specific measuring instruments. The
      Moorehead-Ardelt Quality-of-Life Questionnaire II (MA II) is an obesity-specific
      instrument widely used in bariatric surgery. The objective of this study was to
      translate and validate the MA II in Greek language. The study included the
      translation of the MA II followed by cross-validation with the Greek version of
      36-item Short Form Health Survey (SF-36) and a Visual Analogue Scale (VAS) in
      subjects visiting an obesity clinic. Internal consistency was indicated by
      Cronbach's alpha coefficient and test-retest reliability by intraclass
      correlation coefficient (ICC). Construct validity was studied using Pearson's
      correlations between the MA II, the SF-36 and the VAS. A total of 175 patients
      were enrolled in the study. Test-retest analysis was applied to 40 patients with
      a 15-day interval. A very good internal consistency with Cronbach's alpha
      coefficient of 0.85 was shown. Excellent test-retest reliability was observed
      with an overall ICC of 0.981. Significant correlations between the Greek MA II
      and the other instruments as well as of each item of the MA II with the scores of
      SF-36 and the VAS indicated high construct and convergent validity. A negative
      correlation between the translated MA II total score and BMI confirmed high
      clinical validity. The Greek version of the MA II questionnaire has been
      generated and shown to be valid and reliable in measuring HRQoL in morbidly obese
      patients before and after bariatric surgery.

PMID- 22411572
TI  - Duodenal-jejunal bypass surgery enhances glucose tolerance and beta-cell function
      in Western diet obese rats.
AB  - BACKGROUND: The aim of this study was to investigate the effect of the duodenal
      jejunal bypass (DJB) on glucose homeostasis and islet insulin secretion in
      Western diet (WD) obese rats. METHODS: Male Wistar rats received a standard
      rodent chow diet (CTL group) or WD ad libitum. After 32 weeks of diet, WD rats
      were submitted to duodenal-jejunal bypass (WD DJB) or sham (WD S-DJB) operation.
      Intraperitoneal (ip) glucose tolerance test was performed 1 week after surgery.
      Body weight, fat pad depots, glycemia, insulinemia, HOMA-IR, and glucose-induced
      insulin secretion were evaluated 1 month after surgery. RESULTS: Body weight and
      fat pads of the WD group were higher than those of the CTL group. Sham and DJB
      surgeries did not alter these parameters. WD and WD S-DJB rats were glucose
      intolerant, insulin resistant, and hyperinsulinemic. WD DJB rats showed similar
      glucose tolerance, insulin sensitivity, and plasma insulin levels to those of CTL
      rats. WD rats presented higher fat and glycogen contents in the liver. DJB
      surgery normalized fat and glycogen stores in the liver of the WD DJB group.
      Insulin release at 11.1-mM glucose, in isolated islets from WD and WD S-DJB rats,
      was higher than from islets of CTL rats. In contrast, DJB surgery improves the
      beta-cell secretory capacity with increased glucose-induced secretion at 5.6-,
      11.1-, and 22.2-mM glucose in WD DJB islets, compared with CTL islets.
      CONCLUSIONS: DJB surgery improves glucose homeostasis and enhances beta-cell
      glucose responsiveness in rats submitted to the WD diet without any modification
      in adiposity.

PMID- 22411573
TI  - Association of ghrelin receptor promoter polymorphisms with weight loss following
      Roux-en-Y gastric bypass surgery.
AB  - BACKGROUND: Ghrelin plays a role in appetite and has been hypothesized to play a
      role in the mechanism of Roux-en-Y gastric bypass (RYGB) surgery. Single
      nucleotide polymorphisms (SNPs) in the promoter region of its receptor gene
      (growth hormone secretagogue receptor type 1a--GHSR) have also been associated
      with weight loss outcomes following long-term dietary intervention in adults with
      impaired glucose tolerance. Our objectives were to evaluate changes in serum
      ghrelin levels and determine the effect of GHSR promoter polymorphisms on post
      RYGB surgery weight loss. METHODS: Preoperative and 6-month postoperative serum
      ghrelin levels were measured in 37 patients with extreme obesity undergoing RYGB
      surgery. Total ghrelin was also measured in liver tissue collected
      intraoperatively. Association analysis between genotypes for SNPs rs9819506 and
      rs490683 in the promoter region of the GHSR gene and weight loss outcomes in the
      30 months following surgery was performed in over 650 RYGB patients. RESULTS:
      Serum ghrelin levels increased after RYGB surgery. Weight loss trajectories were
      significantly different using an additive model for both ghrelin SNPs, with
      patients homozygous for the rs490683 CC genotype exhibiting the most weight loss.
      Weight loss trajectories were also different using a dominant model. The rs490683
      risk allele demonstrated decreased promoter activity in vitro. CONCLUSIONS: The
      role of increased ghrelin levels in weight loss outcomes following RYGB surgery
      may be influenced by variation in the GHSR gene.

PMID- 22411574
TI  - Standardized AP radiographs do not provide reliable diagnostic measures for the
      assessment of acetabular retroversion.
AB  - Diagnosis of acetabular retroversion is essential in femoroacetabular impingement
      (FAI), but its assessment from radiographs is complicated by pelvic tilt and the
      two-dimensional nature of plain films. We performed a study to validate the
      diagnostic accuracy of the cross-over sign (COS) and the posterior wall sign
      (PWS) in identifying acetabular retroversion. COS and PWS were evaluated from
      radiographs and computed tomography (CT) scans as the standard of reference in 50
      hips of subjects with symptoms of FAI. A CT-based method using three-dimensional
      (3D) models was developed to measure the COS, PWS, true acetabular version, and
      pelvic tilt relative to the anterior pelvic plane. The new CT-based method aimed
      to eliminate errors resulting from variations in the position and orientation of
      the pelvis during imaging. A low level of agreement for COS and PWS was found
      between radiographs and CT scans. A positive COS strongly correlated with pelvic
      tilt. These results suggest that COS and PWS determined from anteroposterior
      radiographs are considerably limited by pelvic tilt and inherent limitations of
      radiographs. Their use as the sole basis for deciding whether or not surgical
      intervention is indicated seems questionable.

PMID- 22411575
TI  - Barry M. Trost. Interview by Stefan Kirsch.

PMID- 22411577
TI  - Impact of antihypertensive drugs on TNF-like weak inducer of apoptosis.

PMID- 22411576
TI  - The amber theory of Lyme arthritis: initial description and clinical
      implications.
AB  - Lyme arthritis differs in many respects from other bacterial causes of arthritis.
      Based on an observation made for a patient with Lyme arthritis, we propose that
      the pathogenesis of joint swelling in Lyme arthritis is due to the introduction
      into the joint space of non-viable spirochetes or more likely spirochetal debris
      enmeshed in a host-derived fibrinous or collagenous matrix. This "amber"
      hypothesis can account for the clinical and laboratory features of Lyme arthritis
      and is amenable to experimental validation. Validation would directly impact the
      clinical management of patients with Lyme arthritis.

PMID- 22411578
TI  - Efficient gene therapy based targeting system for the treatment of inoperable
      tumors.
AB  - BACKGROUND: A considerable percentage of tumors are not amenable to surgery. We
      have designed a simple and powerful targeting system that offers an alternative
      option for the multi-component pre-targeting strategies used clinically. This
      targeting system can be used for any type of solid tumors independent of the
      tumor type, thereby omitting the need to engineer unique antibodies for each
      specific application or tumour type. In the present study, we show the expression
      of a chimeric fusion protein, which contains the low-density lipoprotein receptor
      transmembrane domains and avidin, after local gene transfer and its ability to
      bind biotinylated compounds in vivo. METHODS: Semliki Forest virus and lentivirus
      vectors were used to express the fusion protein with a high affinity binding site
      for biotinylated compounds in the tumor. Three different animal models and
      imaging modalities were used for the demonstration of the functionality and
      efficacy of the targeting system in vitro and in vivo. RESULTS: We demonstrate
      targeting of biotinylated compounds after local gene transfer in vivo using two
      different gene transfer vectors. The findings were confirmed by
      immunohistochemistry, single-photon emission computed tomography and magnetic
      resonance imaging. The therapeutic efficacy was tested in a syngeneic rat glioma
      model by injecting biotinylated-(90) Yttrium into the tail vein of glioma bearing
      rats. The study demonstrates that animals, which were treated by using the gene
      therapy based targeting system, lived significantly longer than control animals.
      CONCLUSIONS: Our gene therapy based targeting system is a promising tool for the
      treatment of inoperable tumors and other disease conditions, as well as
      diagnostic imaging.

PMID- 22411579
TI  - Effects of implicit visual feedback distortion on human gait.
AB  - Gait rehabilitation after stroke often utilizes treadmill training delivered by
      either therapists or robotic devices. However, clinical results have shown no
      benefit from this modality when compared to usual care. On the contrary, results
      were inferior; perhaps, because in its present form it is not interactive and at
      least for stroke, central pattern generators at the spinal level do not appear to
      be the key to promote recovery. To enable gait therapy to be more effective,
      therapy must be interactive and visual feedback appears to be an important option
      to engage patients' participation. In this study, we tested healthy subjects to
      see whether an implicit "visual feedback distortion" influences gait spatial
      pattern. Subjects were not aware of the visual distortion nor did they realize
      changes in their gait pattern. The visual feedback of step length symmetry was
      distorted so that subjects perceived their step length as being asymmetric during
      treadmill training. We found that a gradual distortion of visual feedback,
      without explicit knowledge of the manipulation, systematically modulated gait
      step length away from symmetry and that the visual distortion effect was robust
      even in the presence of cognitive load. This indicates that although the visual
      feedback display used in this study did not create a conscious and vivid
      sensation of self-motion (the properties of the optical flow), experimental
      modifications of visual information of subjects' movement were found to cause
      implicit gait modulation. Nevertheless, our results indicate that modulation with
      visual distortion may require cognitive resources because during the distraction
      task, the amount of gait modulation was reduced. Our results suggest that a
      therapeutic program involving visual feedback distortion, in the context of gait
      rehabilitation, may provide an effective way to help subjects correct gait
      patterns, thereby improving the outcome of rehabilitation.

PMID- 22411580
TI  - The bottle and the glass say to me: "pour!".
AB  - The present study aimed at determining whether the observation of two
      functionally compatible artefacts, that is which potentially concur in achieving
      a specific function, automatically activates a motor programme of interaction
      between the two objects. To this purpose, an interference paradigm was used
      during which an artefact (a bottle filled with orange juice), target of a
      reaching-grasping and lifting sequence, was presented alone or with a non-target
      object (distractor) of the same or different semantic category and functionally
      compatible or not. In experiment 1, the bottle was presented alone or with an
      artefact (a sphere), or a natural (an apple) distractor. In experiment 2, the
      bottle was presented with either the apple or a glass (an artefact) filled with
      orange juice, whereas in experiment 3, either an empty or a filled glass was
      presented. In the control experiment 4, we compared the kinematics of reaching
      grasping and pouring with those of reaching-grasping and lifting. The kinematics
      of reach, grasp and lift was affected by distractor presentation. However, no
      difference was observed between two distractors that belonged to different
      semantic categories. In contrast, the presence of the empty rather filled glass
      affected the kinematics of the actual grasp. This suggests that an actually
      functional compatibility between target (the bottle) and distractor (the empty
      glass) was necessary to activate automatically a programme of interaction (i.e.
      pouring) between the two artefacts. This programme affected the programme
      actually executed (i.e. lifting). The results of the present study indicate that,
      in addition to affordances related to intrinsic object properties, "working
      affordances" related to a specific use of an artefact with another object can be
      activated on the basis of functional compatibility.

PMID- 22411581
TI  - Multisensory integration in the estimation of walked distances.
AB  - When walking through space, both dynamic visual information (optic flow) and body
      based information (proprioceptive and vestibular) jointly specify the magnitude
      of distance travelled. While recent evidence has demonstrated the extent to which
      each of these cues can be used independently, less is known about how they are
      integrated when simultaneously present. Many studies have shown that sensory
      information is integrated using a weighted linear sum, yet little is known about
      whether this holds true for the integration of visual and body-based cues for
      travelled distance perception. In this study using Virtual Reality technologies,
      participants first travelled a predefined distance and subsequently matched this
      distance by adjusting an egocentric, in-depth target. The visual stimulus
      consisted of a long hallway and was presented in stereo via a head-mounted
      display. Body-based cues were provided either by walking in a fully tracked free
      walking space (Exp. 1) or by being passively moved in a wheelchair (Exp. 2).
      Travelled distances were provided either through optic flow alone, body-based
      cues alone or through both cues combined. In the combined condition, visually
      specified distances were either congruent (1.0*) or incongruent (0.7* or 1.4*)
      with distances specified by body-based cues. Responses reflect a consistent
      combined effect of both visual and body-based information, with an overall higher
      influence of body-based cues when walking and a higher influence of visual cues
      during passive movement. When comparing the results of Experiments 1 and 2, it is
      clear that both proprioceptive and vestibular cues contribute to travelled
      distance estimates during walking. These observed results were effectively
      described using a basic linear weighting model.

PMID- 22411582
TI  - Reaching to recover balance in unpredictable circumstances: is online visual
      control of the reach-to-grasp reaction necessary or sufficient?
AB  - Reaching to grasp an object for support is a common and functionally important
      response to sudden balance perturbation. The need to react very rapidly (to
      prevent falling) imposes temporal constraints on acquisition and processing of
      the visuospatial information (VSI) needed to guide the reaching movement.
      Previous results suggested that the CNS may deal with these constraints by using
      VSI stored in memory proactively, prior to perturbation onset; however, the
      extent to which online visual control is necessary or sufficient to guide these
      reactions has not been established. This study examined the speed, accuracy, and
      effectiveness of perturbation-evoked reach-to-grasp reactions when forced to rely
      entirely on either online- or stored-VSI by using liquid-crystal goggles to
      occlude vision either before or after perturbation onset. The reactions were
      evoked, in twelve healthy young adults, via sudden unpredictable antero-posterior
      platform translation (barriers deterred stepping reactions). Prior to
      perturbation onset, a small cylindrical handhold was positioned unpredictably (by
      a motor-driven device) at one of four locations in front of the subject. Results
      indicated that equilibrium could be recovered successfully by grasping the
      handhold using either online-VSI or stored-VSI to guide the arm reaction;
      however, both sources of VSI were required for optimal performance. Reach
      initiation and arm movement were slowed when dependent on online-VSI, whereas
      reach accuracy and grip formation were impaired when dependent on stored-VSI.
      Comparison with normal-VSI trials suggests that both sources of VSI are utilized
      when grasping a small handhold for support under normal visual conditions, with
      stored-VSI predominating during initiation/transport and online-VSI contributing
      primarily to final target acquisition/prehension.

PMID- 22411583
TI  - Hydration level is an internal variable for computing motivation to obtain water
      rewards in monkeys.
AB  - In the process of motivation to engage in a behavior, valuation of the expected
      outcome is comprised of not only external variables (i.e., incentives) but also
      internal variables (i.e., drive). However, the exact neural mechanism that
      integrates these variables for the computation of motivational value remains
      unclear. Besides, the signal of physiological needs, which serves as the primary
      internal variable for this computation, remains to be identified. Concerning
      fluid rewards, the osmolality level, one of the physiological indices for the
      level of thirst, may be an internal variable for valuation, since an increase in
      the osmolality level induces drinking behavior. Here, to examine the relationship
      between osmolality and the motivational value of a water reward, we repeatedly
      measured the blood osmolality level, while 2 monkeys continuously performed an
      instrumental task until they spontaneously stopped. We found that, as the total
      amount of water earned increased, the osmolality level progressively decreased
      (i.e., the hydration level increased) in an individual-dependent manner. There
      was a significant negative correlation between the error rate of the task (the
      proportion of trials with low motivation) and the osmolality level. We also found
      that the increase in the error rate with reward accumulation can be well
      explained by a formula describing the changes in the osmolality level. These
      results provide a biologically supported computational formula for the
      motivational value of a water reward that depends on the hydration level,
      enabling us to identify the neural mechanism that integrates internal and
      external variables.

PMID- 22411585
TI  - Colonoscopy as a useful tool in determining the transition zone in transanal
      endorectal pull-through in Hirschsprung's disease.

PMID- 22411584
TI  - mRNA expression of adipocytokines and glucocorticoid-related genes are associated
      with downregulation of E-cadherin mRNA in colorectal adenocarcinomas.
AB  - BACKGROUND: There is a consistently reported relationship between the incidence
      of colon cancer and obesity. It is thought that adipose tissue, particularly
      visceral fat, which secretes systemic factors that alter immunological, metabolic
      and endocrine milieu and promotes insulin resistance by producing adipocytokines,
      is important in cancer progression. Systemic high concentrations of
      adipocytokines, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin
      6 (IL-6), and glucocorticoid metabolism-related genes have been associated with
      gastrointestinal cancer. However, limited information exists about the expression
      of these cytokines within tumour tissue. MATERIAL AND METHODS: mRNA expression of
      TNF-alpha, IL-6,IL-8, IL-10, IL-1RN, glucocorticoid receptor alpha (GR-alpha),
      11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), plasminogen activator
      inhibitor-1 (PAI-1), Slug, vimentin, Snail and E-cadherin was analysed in paired
      samples of tumour tissue and normal mucosa in 60 surgical patients for Dukes B
      and C colorectal adenocarcinomas using quantitative reverse transcription PCR and
      microarray technology. The mRNA expression level of analysed genes was compared
      between tumour tissue and normal mucosa from the same patients, and a correlation
      to mRNA expression of E-cadherin in the same tissue samples was also performed.
      RESULTS: A highly significant difference in mRNA expression level of several of
      the analysed genes was observed between tumour tissue and the normal intestinal
      mucosa. Inverse correlation between mRNA expression of 11betaHSD1, IL-6, GR-alpha
      and PAI-1 on one hand and mRNA expression of E-cadherin on the other hand was
      observed. CONCLUSION: Results show that the adipocytokines and glucocorticoid
      metabolism-related genes are overexpressed in colorectal adenocarcinomas, and
      expression of these genes is associated with the downregulation of E-cadherin
      mRNA, connecting these genes to carcinogenesis and progression of colorectal
      cancer.

PMID- 22411586
TI  - Cobalt-doping-induced synthesis of ceria nanodisks and their significantly
      enhanced catalytic activity.
AB  - High-quality cobalt-doped ceria nanostructures with triangular column, triangular
      slab, and disklike shapes are synthesized by tuning the doping amount of cobalt
      nitrate in a facile hydrothermal reaction. The cobalt-doped ceria nanodisks
      display significantly enhanced catalytic activity in CO oxidation due to exposed
      highly active crystal planes and the presence of numerous surface defects.

PMID- 22411587
TI  - Nerve growth factor stimulates cellular proliferation of human epithelial ovarian
      cancer.
AB  - Due to its ability to induce vascular endothelial growth factor expression and
      proliferation, migration, and vasculogenesis of endothelial cells, nerve growth
      factor (NGF) has been considered as an angiogenic factor in epithelial ovarian
      cancer (EOC). In this work, we evaluated the angiogenic and proliferative mRNA
      expression profiles of EOC and addressed the responsiveness of EOC explants to
      NGF stimulation. Twenty EOC samples were obtained from Obstetrics and Gynecology
      Department, University of Chile's Clinical Hospital. Global gene expression
      profiles of selected poorly differentiated serous EOC samples were obtained with
      DNA oligonucleotide microarrays. In addition, EOC explants were subjected to NGF
      stimulation and levels of p-AKT, BAX, BCL2, Ki-67, c-MYC, and FOXL2 proteins were
      determined by immunohistochemistry. Results showed that mRNAs coding for specific
      transcriptional regulators and antiapoptotic components of the NGF signaling
      pathway were upregulated in EOC cells. At the protein level, key members of the
      NGF pathway including p-AKT, BCL2/BAX, Ki-67, and c-MYC were found increased,
      while FOXL2 was decreased in response to NGF stimulation. These findings strongly
      suggest that NGF stimulates cellular proliferation of human EOC.

PMID- 22411588
TI  - Trajectories of mental health before and after old-age and disability retirement:
      a register-based study on purchases of psychotropic drugs.
AB  - OBJECTIVES: Retirement from paid work is a major life event facing increasingly
      large numbers of people in the coming years. We examined trajectories of mental
      health five years before and five years after old-age and disability retirement
      using data on purchases of psychotropic drugs. METHODS: The study included all
      employees from the City of Helsinki, Finland, retiring between 2000-2008 due to
      old age (N=4456) or disability (N=2549). Purchases of psychotropic drugs were
      analyzed in 20 3-month intervals before and after retirement using graphical
      methods and growth curve models. RESULTS: Old-age retirement was unrelated to
      purchases of psychotropic drugs. Among disability retirees, psychotropic
      medication tripled before retirement. The average increase was 0.95 [95%
      confidence interval (95% CI) 0.73-1.16] daily defined doses (DDD) 5-1.5 years
      before retirement; from 1.5 years until retirement it was 5.68 DDD (95% CI 5.33
      6.03) for each 3-month interval. After disability retirement, purchases of
      antidepressants decreased on average by 0.40 DDD (95% CI 0.57-0.23) for each 3
      month interval, those of hypnotics and sedatives increased by 0.30 DDD (95% CI
      0.12-0.47), and no changes were seen for other psychotropic drugs. The changes
      before and after retirement were largest among those who retired due to mental
      disorders and those whose retirement had been granted as temporary. CONCLUSIONS:
      While no overall decrease in psychotropic medication after retirement was
      observed, purchases of antidepressants decreased after disability retirement.
      Long-term trajectories suggest that disability retirement might be prevented if
      mental health problems were tackled more efficiently earlier in the pre
      retirement period.

PMID- 22411590
TI  - Oral and hand movement speeds are associated with expressive language ability in
      children with speech sound disorder.
AB  - This study tested the hypothesis that children with speech sound disorder have
      generalized slowed motor speeds. It evaluated associations among oral and hand
      motor speeds and measures of speech (articulation and phonology) and language
      (receptive vocabulary, sentence comprehension, sentence imitation), in 11
      children with moderate to severe SSD and 11 controls. Syllable durations from a
      syllable repetition task served as an estimate of maximal oral movement speed. In
      two imitation tasks, nonwords and clapped rhythms, unstressed vowel durations and
      quarter-note clap intervals served as estimates of oral and hand movement speed,
      respectively. Syllable durations were significantly correlated with vowel
      durations and hand clap intervals. Sentence imitation was correlated with all
      three timed movement measures. Clustering on syllable repetition durations
      produced three clusters that also differed in sentence imitation scores. Results
      are consistent with limited movement speeds across motor systems and SSD subtypes
      defined by motor speeds as a corollary of expressive language abilities.

PMID- 22411589
TI  - Immunophenotypic characterization of enteric neural crest cells in the developing
      avian colorectum.
AB  - BACKGROUND: The enteric nervous system (ENS) develops from neural crest-derived
      cells that migrate along the intestine to form two plexuses of neurons and glia.
      While the major features of ENS development are conserved across species, minor
      differences exist, especially in the colorectum. Given the embryologic and
      disease-related importance of the distal ENS, the aim of this study was to
      characterize the migration and differentiation of enteric neural crest-derived
      cells (ENCCs) in the colorectum of avian embryos. RESULTS: Using normal chick
      embryos and vagal neural tube transplants from green fluorescent protein (GFP) 
      transgenic chick embryos, we find ENCCs entering the colon at embryonic day (E)
      6.5, with colonization complete by E8. Undifferentiated ENCCs at the wavefront
      express HNK-1, N-cadherin, Sox10, p75, and L1CAM. By E7, differentiation begins
      in the proximal colon, with L1CAM and Sox10 becoming restricted to neuronal and
      glial lineages, respectively. By E8, multiple markers of differentiation are
      expressed along the entire colorectum. CONCLUSIONS: Our results establish the
      pattern of ENCC migration and differentiation in the chick colorectum,
      demonstrate the conservation of marker expression across species, highlight a
      range of markers, including neuronal cell adhesion molecules, which label cells
      at the wavefront, and provide a framework for future studies in avian ENS
      development.

PMID- 22411591
TI  - Do irrelevant sounds impair the maintenance of all characteristics of speech in
      memory?
AB  - Several studies have shown that maintaining in memory some attributes of speech,
      such as the content or pitch of an interlocutor's message, is markedly reduced in
      the presence of background sounds made of spectrotemporal variations. However,
      experimental paradigms showing this interference have only focused on one
      attribute of speech at a time, and thus differ from real-life situations in which
      several attributes have to be memorized and maintained simultaneously. It is
      possible that the interference is even greater in such a case and can occur for a
      broader range of background sounds. We developed a paradigm in which participants
      had to maintain the content, pitch and speaker size of auditorily presented
      speech information and used various auditory distractors to generate
      interference. We found that only distractors with spectrotemporal variations
      impaired the detection, which shows that similar interference mechanisms occur
      whether there are one or more speech attributes to maintain in memory. A high
      percentage of false alarms was observed with these distractors, suggesting that
      spectrotemporal variations not only weaken but also modify the information
      maintained in memory. Lastly, we found that participants were unaware of the
      interference. These results are similar to those observed in the visual modality.

PMID- 22411592
TI  - Determiner primes as facilitators of lexical retrieval in English.
AB  - Gender priming studies have demonstrated facilitation of noun production
      following pre-activation of a target noun's grammatical gender. Findings provide
      support for models in which syntactic information relating to words is stored
      within the lexicon and activated during lexical retrieval. Priming effects are
      observed in the context of determiner plus noun phrase production. Few studies
      demonstrate gender priming effects in bare noun production (i.e., nouns in
      isolation). We investigated the effects of English determiner primes on bare mass
      and count noun production. In two experiments, participants named pictures after
      exposure to primes involving congruent, incongruent and neutral determiners.
      Facilitation of noun production by congruent and neutral determiner primes was
      found in both experiments. The results suggest that noun phrase syntax is
      activated in lexical retrieval, even when not explicitly required for production.
      Post hoc analysis of the relative frequency of congruent and incongruent prime
      target pairs provides support for a frequency-based interpretation of the data.

PMID- 22411593
TI  - Symmetrical femoral vein bubble caused by decompression illness.

PMID- 22411594
TI  - How well informed are patients when leaving the emergency department? comparing
      information provided and information retained.
AB  - STUDY OBJECTIVE: Patients discharged from the emergency department (ED) should be
      informed comprehensively and accurately about the diagnosis, future examinations
      and follow-up care. This study investigates: (1) how comprehensively patients are
      informed by physicians on discharge; (2) how accurately patients remember this
      information after discharge; (3) how well informed overall patients leave the ED;
      and (4) whether informedness relates to patient satisfaction. METHODS: This study
      compares: (1) information given during discharge conversations, based on audio
      recordings of the conversations, with (2) accuracy of patient recall of this
      information, based on postdischarge interviews. During these interviews, the
      authors also assessed (3) amount and accuracy of information provided during
      treatment. Furthermore, the authors obtained (4) satisfaction ratings by
      physicians and patients. Data were collected for 96 patients during 20 shifts.
      RESULTS: Sufficient information was provided in 83% of discharge conversations.
      Patients correctly recalled 82% of information received about diagnosis, 56%
      about examinations planned and 72% about follow-up treatments. Information
      related to medication was most prone to forgetting or distortion. Altogether, 43%
      of the patients left the ED correctly informed about diagnosis, planned
      examinations and follow-up. Patient satisfaction ratings were high (mean 4.7 on a
      5-point Likert Scale) and not related to informedness of the patient.
      CONCLUSIONS: Patients had important information deficits when leaving the ED, and
      information transmission needs to be improved. The physician-patient discharge
      conversation seems an ideal opportunity for enhancing patient informedness.
      Standardisation of discharge procedures and training physicians in how to ensure
      that patients actually understand the information provided are needed.

PMID- 22411595
TI  - Severe emphysematous pyelonephritis combined with pneumobilia.

PMID- 22411596
TI  - Comparison of resident and mid-level provider productivity and patient
      satisfaction in an emergency department fast track.
AB  - OBJECTIVE: To evaluate productivity of mid-level providers (MLPs) compared with
      emergency medicine (EM) resident physicians in an emergency department (ED) low
      acuity area, and to compare patient satisfaction when cared for by MLPs versus EM
      residents. METHODS: This was a retrospective review of EM resident physicians and
      MLPs in an ED low acuity area. The number of patients seen and relative value
      units (RVUs) generated per clinical hour worked were evaluated. A t test was used
      to compare resident and MLP productivity. Additionally, patients were
      prospectively surveyed to assess satisfaction, using survey items based on the
      Press-Ganey survey. Non-parametric statistics were used to analyse patient
      satisfaction scores. RESULTS: MLPs treated 2.21 patients per hour (CI +/-0.09),
      while resident physicians treated 1.53 patients per hour (CI +/-0.08). MLPs
      generated 4.01 RVUs per hour (CI +/-0.18) while resident physicians generated
      3.14 RVUs per hour (CI +/-0.18). Resident physicians generated 2.07 RVUs per
      patient (CI +/-0.08) while MLPs generated 1.82 RVUs per patient (CI +/-0.03;
      p<0.001). Of the 201 completed satisfaction surveys, 126 patients were seen by
      MLPs and 75 were seen by residents. Overall patients were highly satisfied with
      their ED visit. There were no differences in any survey responses based on
      provider type or resident level of training. CONCLUSION: In a low acuity area of
      the ED, MLPs treated more patients per hour and generated more RVUs per hour than
      EM resident physicians. However, resident physicians generated more RVUs per
      patient. Patient satisfaction did not differ.

PMID- 22411597
TI  - Nose and vein, speed and pain: comparing the use of intranasal diamorphine and
      intravenous morphine in a Scottish paediatric emergency department.
AB  - BACKGROUND: Urgent analgesia is essential for all children who present in severe
      pain, but difficulties in obtaining venous access can delay the use of adequate
      opiate analgesia. Intranasal diamorphine (IND) is now in use in around 60% of
      emergency departments and is the preferred choice of analgesia as reported by
      both parents and healthcare professionals. While IND has similar efficacy to
      intramuscular morphine in children, no study has compared its use against the
      current gold standard, intravenous morphine (IVM). METHODS: IND was introduced to
      the Royal Aberdeen Children's Hospital on 24 December 2009. A retrospective case
      series was constructed to compare its clinical performance with its predecessor
      IVM. Three unexplored factors were investigated: time to opiate analgesia, the
      requirement for further analgesia when still in the emergency department and the
      effect of simple coanalgesia (eg, paracetamol/ibuprofen) on these requirements.
      RESULTS: 297 patients were eligible for the study (147 IND, 150 IVM) over a 28
      month period. There was a non-significant trend to a longer median time to
      administration of analgesia in patients receiving IND (p=0.170). Patients who
      received IND were less likely to require further analgesia (p<0.001). Both groups
      were less likely to require further analgesia when simple coanalgesia was given
      (p=0.049). CONCLUSION: The authors found no significant difference in time to
      administration of analgesia between agents, but a learning curve has been
      identified. Sustained effort should be placed on the use of simple coanalgesia.
      The clinical performance of IND compares favourably with IVM in children with
      severe pain, and it remains an appropriate preferred agent.

PMID- 22411598
TI  - Do emergency physicians and radiologists reliably interpret pelvic radiographs
      obtained as part of a trauma series?
AB  - INTRODUCTION: Interpretation of pelvic radiography is an important component of
      the primary survey and is commonly performed by emergency physicians.
      Radiologists bring unique skills to trauma care, including choice of imaging
      modality and image interpretation. It is not clear if this limited resource is
      most efficiently used in the resuscitation room. No studies have compared
      radiologists and trauma clinicians in their ability to interpret pelvic
      radiographs following trauma. OBJECTIVE: To determine the sensitivity and
      specificity of trauma experienced and trauma inexperienced emergency physicians
      in detecting pelvic fractures compared with radiologists, the latter subgroup
      combined report being used as the gold standard. SETTING AND METHODS: Prospective
      cohort study conducted in two large teaching hospitals in central London. All
      participants reviewed 144 consecutive pelvic radiographs performed each as part
      of a 'trauma series' and known to have undergone concomitant pelvic CT imaging.
      RESULTS: No statistically significant difference was found between radiologists
      and emergency physicians from a trauma centre in pelvic radiograph
      interpretation. Radiologist reporting was associated with an improved specificity
      compared with emergency physicians working in a non-trauma hospital (p=0.049).
      The study population missed 30% of fractures on plain radiography against the
      gold standard of CT. DISCUSSION: The ability to interpret trauma series pelvic
      radiographs is comparable between emergency physicians and radiologists. If this
      were also true of trauma chest radiographs, then the most valuable use of the
      radiologist may not be the resuscitation room but in rapid reporting of more
      complex imaging techniques. However, plain radiography is insensitive for pelvic
      fracture detection compared with CT, even in expert hands.

PMID- 22411599
TI  - Calcium channel blocker use and serum ferritin in adults with hypertension.
AB  - Iron overload cardiomyopathy is becoming more prevalent, and early recognition
      and intervention may alter outcomes. Calcium channels are key transporters of
      iron under iron-overloaded conditions, and potentially represent a new
      therapeutic target for iron overload. The purpose of this study was to examine
      the relationship between Calcium channel blocker (CCB) use and serum ferritin
      among adults with diagnosed hypertension. We analyzed the nationally
      representative NHANES (National Health and Nutrition Examination Survey) 1999
      2002 for adults >=40 years with diagnosed hypertension. The association between
      CCBs and serum ferritin was assessed using a t-test and adjusted multiple
      regressions.The study population included 2143 individuals (representing 37.4
      million individuals, 42.0 % males). 12.6 % of the population reported taking CCBs
      in the last month. Individuals taking CCBs had lower mean serum ferritin (129.3
      ng/mL versus 154.5 ng/mL, p = 0.02). After adjusting for age, sex, menopause and
      hysterectomy status for women, race/ethnicity, and C-reactive protein, mean serum
      ferritin for individuals taking CCBs was 26.3 ng/mL lower than for those not
      taking CCBs (p = 0.01). In an adjusted regression, individuals who took CCBs and
      had a daily vitamin C intake of >=500 mg had a mean serum ferritin that was 60.1
      ng/mL lower than people not taking CCBs and with daily vitamin C < 500 mg (p <
      0.001). In conclusion, this study found an association between use of CCBs and
      lower serum ferritin levels in individuals with hypertension. Further studies are
      needed to assess the possible use of CCBs as non-traditional chelating agents for
      treatment of iron overload cardiomyopathy.

PMID- 22411600
TI  - Pretreatment with AT-101 enhances tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL)-induced apoptosis of breast cancer cells by inducing
      death receptors 4 and 5 protein levels.
AB  - PURPOSE: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a
      member of the TNF superfamily and has been shown to induce extrinsic pathway of
      apoptosis in many types of cancer cells. AT-101, an (-)-enantiomer of gossypol,
      is a potent anticancer agent that is shown to be an inhibitor of Bcl-2/Bcl-XL. In
      this study, we searched whether pretreatment with either of these drugs would
      result in the enhancement of apoptosis through induction of death receptors and
      activation of mitochondrial pathways within breast cancer cells. METHODS: Human
      breast cancer (MCF-7 and MDA-MB-231) and normal breast cells (MCF-10A) were
      treated with drugs alone/in combination/sequentially. XTT cell viability assay
      was used to evaluate cytotoxicity. For showing apoptosis, both DNA Fragmentation
      and caspase 3/7 activity measurements were done. ELISA and Western blot analysis
      were done to assess DR4 and DR5 protein levels. The expression levels of
      apoptotic proteins were assessed by human apoptosis antibody array. RESULTS: The
      sequential treatment of AT-101 followed by TRAIL resulted in significant
      synergistic cytotoxicity and apoptosis. Moreover, pretreatment of breast cancer
      cells with AT-101 and then with TRAIL caused enhancement of the expression levels
      of DR4 and DR5 in both cancer cell lines, suggesting that these cells were under
      strong apoptotic stimuli. CONCLUSIONS: These findings all together, strongly
      suggest that pretreatment with AT-101 enhances TRAIL-induced death-inducing
      signaling complex resulting in the engagement of the mitochondrial pathway to
      apoptosis in breast cancer cells. These promising, preliminary results make AT
      101 and TRAIL a novel combination treatment candidate for breast cancer.

PMID- 22411601
TI  - Testicular torsion.

PMID- 22411602
TI  - Acute limb ischaemia.

PMID- 22411603
TI  - Tackling the single best answer question  in the final FRCA examination.

PMID- 22411604
TI  - Acute appendicitis.

PMID- 22411605
TI  - Nuclear receptors and AMPK: resetting metabolism.
AB  - Obesity, and in particular central adiposity, is a key feature of metabolic
      syndrome, which includes trends toward increased triglycerides, insulin
      resistance, high blood pressure, hypercholesterolemia, and heart disease. It has
      a prevalence of 25% or more and is a dominant component of the health care
      budgets in Western societies. In addition to genetic causes, high-fat diets and
      disrupted sleep patterns have major influences on the development of metabolic
      syndrome. Recent studies have demonstrated active roles for the nuclear receptor
      superfamily and the energy-sensing kinase adenosine monophosphate (AMP)-activated
      protein kinase (AMPK) in regulating metabolism and circadian rhythm. In this
      chapter, we review these findings and attempt to develop a better understanding
      of the interplay between metabolism and circadian rhythm and their coordinated
      regulation by nuclear receptors and AMPK. This supraregulatory network may be
      considered a target for novel therapeutic applications against metabolic
      syndrome.

PMID- 22411606
TI  - Calcium alginate nanoparticles synthesized through a novel interfacial cross
      linking method as a potential protein drug delivery system.
AB  - The goal of this research work was to develop a novel technique to synthesize
      calcium alginate nanoparticles using pharmaceutically relevant microemulsions.
      Stable microemulsion-based reactors were prepared using aqueous sodium alginate,
      aqueous calcium chloride, dioctyl sodium sulfosuccinate (DOSS), and isopropyl
      myristate. The reactor microemulsions were characterized via conductivity and
      dynamic light scattering (DLS) experiments. The conductivity data indicated
      composition- and reagent-dependent variations in electrical conductivity when the
      aqueous phase containing reagents were present at or above a Wo (Wo =
      [DOSS]/[water]) value of 14. The reactor microemulsions were of approximately 6
      nm sized droplets. When the reactor microemulsions were mixed and sonicated for 1
      h approximately, 350-nm-sized calcium alginate nanoparticles were produced, as
      indicated by DLS measurements. The particles were isolated and characterized via
      low-vacuum scanning electron microscopy. The electron micrographs corroborate the
      DLS results. The nanoparticles were evaluated as a drug delivery system by
      incorporating bovine serum albumin (BSA) and performing in vitro release and
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) studies. The
      BSA release profile was characterized by an initial burst release followed by a
      sustained-release phase. SDS-PAGE studies indicated that the incorporated protein
      did not suffer covalent aggregation or degradation via fragmentation.

PMID- 22411607
TI  - Protein-protein interaction network-based detection of functionally similar
      proteins within species.
AB  - Although functionally similar proteins across species have been widely studied,
      functionally similar proteins within species showing low sequence similarity have
      not been examined in detail. Identification of these proteins is of significant
      importance for understanding biological functions, evolution of protein families,
      progression of co-evolution, and convergent evolution and others which cannot be
      obtained by detection of functionally similar proteins across species. Here, we
      explored a method of detecting functionally similar proteins within species based
      on graph theory. After denoting protein-protein interaction networks using
      graphs, we split the graphs into subgraphs using the 1-hop method. Proteins with
      functional similarities in a species were detected using a method of modified
      shortest path to compare these subgraphs and to find the eligible optimal
      results. Using seven protein-protein interaction networks and this method, some
      functionally similar proteins with low sequence similarity that cannot detected
      by sequence alignment were identified. By analyzing the results, we found that,
      sometimes, it is difficult to separate homologous from convergent evolution.
      Evaluation of the performance of our method by gene ontology term overlap showed
      that the precision of our method was excellent.

PMID- 22411608
TI  - Remembering David Shephard, MB FRCPC (1930-2011).

PMID- 22411609
TI  - Estrogen treatment prevents gray matter atrophy in experimental autoimmune
      encephalomyelitis.
AB  - Gray matter atrophy is an important correlate to clinical disability in multiple
      sclerosis (MS), and many treatment trials include atrophy as an outcome measure.
      Atrophy has been shown to occur in experimental autoimmune encephalomyelitis
      (EAE), the most commonly used animal model of MS. The clinical severity of EAE is
      reduced in estrogen-reated mice, but it remains unknown whether estrogen
      treatment can reduce gray matter atrophy in EAE. In this study, mice with EAE
      were treated with either estrogen receptor (ER)-alpha ligand or ER-beta ligand,
      and diffusion tensor images (DTI) were collected and neuropathology was
      performed. DTI showed atrophy in the cerebellar gray matter of vehicle-treated
      EAE mice compared with healthy controls but not in ER-alpha or ER-beta ligand
      treated EAE mice. Neuropathology demonstrated that Purkinje cell numbers were
      decreased in vehicle-treated EAE mice, whereas neither ER ligand-treated EAE
      groups showed a decrease. This is the first report of a neuroprotective therapy
      in EAE that unambiguously prevents gray matter atrophy while sparing a major
      neuronal cell type. Fractional anisotropy (FA) in the cerebellar white matter was
      decreased in vehicle- and ER-beta ligand-treated but not in ER-alpha ligand
      treated EAE mice. Inflammatory cell infiltration was increased in vehicle- and ER
      beta ligand-treated but not in ER-alpha ligand-treated EAE mice. Myelin staining
      was decreased in vehicle-treated EAE mice and was spared in both ER ligand
      treated groups. This is consistent with decreased FA as a potential biomarker for
      inflammation rather than myelination or axonal damage in the cerebellum in EAE.

PMID- 22411610
TI  - Efficacy of combined therapy with liposome-encapsulated meglumine antimoniate and
      allopurinol in treatment of canine visceral leishmaniasis.
AB  - An innovative liposomal formulation of meglumine antimoniate (LMA) was recently
      reported to promote both long-term parasite suppression and reduction of
      infectivity to sand flies in dogs with visceral leishmaniasis. However, 5 months
      after treatment, parasites were still found in the bone marrow of all treated
      dogs. In order to improve treatment with LMA, the present study aimed to evaluate
      its efficacy in combination with allopurinol. Mongrel dogs naturally infected
      with Leishmania infantum were treated with six doses of LMA (6.5 mg Sb/kg of body
      weight/dose) given at 4-day intervals, plus allopurinol (20 mg/kg/24 h per os)
      for 140 days. Comparison was made with groups treated with LMA, allopurinol,
      empty liposomes plus allopurinol, empty liposomes, and saline. Dogs remained
      without treatment from day 140 to 200 after the start of treatment. The drug
      combination promoted both clinical improvement of dogs and significant reduction
      in the parasitic load in bone marrow and spleen on days 140 and 200 compared to
      these parameters in the pretreatment period. This is in contrast with the other
      protocols, which did not result in significant reduction of the bone marrow
      parasite load on day 200. Strikingly, the combined treatment, in contrast to the
      other regimens, induced negative quantitative PCR (qPCR) results in the liver of
      100% of the dogs. Both xenodiagnosis and skin parasite determination by qPCR
      indicated that the drug combination was effective in blocking the transmission of
      skin parasites to sand flies. Based on all of the parasitological tests performed
      on day 200, 50% of the animals that received the combined treatment were
      considered cured.

PMID- 22411611
TI  - Impact of prior inappropriate fluconazole dosing on isolation of fluconazole
      nonsusceptible Candida species in hospitalized patients with candidemia.
AB  - Prior use of fluconazole is a modifiable risk factor for the isolation of
      fluconazole-nonsusceptible Candida species. Optimization of the use of
      fluconazole by appropriate dose or duration may be able to minimize the risk of
      resistance. The objective of this study was to evaluate the effects of prior
      fluconazole therapy, including the dose and duration, on fluconazole
      susceptibility among Candida species isolated from hospitalized patients with
      candidemia. A retrospective cohort study of hospitalized patients with a first
      occurrence of nosocomial candidemia, from 2006 to 2009, was carried out. The
      relationships between the initial dose and duration of prior fluconazole therapy
      and the isolation of fluconazole-nonsusceptible Candida species were assessed. An
      initial fluconazole dose greater than 2 mg/kg and less than 6 mg/kg of body
      weight was considered suboptimal. A total of 177 patients were identified, of
      whom 133 patients aged 61 +/- 16 years (56% male, 51% Caucasian, 51% with an
      APACHE II score of >= 15) had candidemia more than 2 days after the hospital
      admission day. Nine of 107 (8%) patients with fluconazole-susceptible Candida
      species and 9 of 26 (35%) patients with fluconazole-nonsusceptible Candida
      species had prior fluconazole exposure (risk ratio [RR], 3.03; 95% confidence
      interval [95% CI], 1.57 to 5.86; P, 0.0022). Preexposure with an initial dose of
      fluconazole greater than 2 mg/kg and less than 6 mg/kg occurred in 3 of 9 (33%)
      and 8 of 9 (89%) patients with fluconazole-susceptible and fluconazole
      nonsusceptible Candida species, respectively (P, 0.0498). We conclude that
      patients with candidemia due to fluconazole-nonsusceptible Candida species were
      more likely to have received prior fluconazole therapy. Suboptimal initial dosing
      of prior fluconazole therapy was associated with candidemia with fluconazole
      nonsusceptible Candida species.

PMID- 22411612
TI  - The maltose ABC transporter in Lactococcus lactis facilitates high-level
      sensitivity to the circular bacteriocin garvicin ML.
AB  - We generated and characterized a series of spontaneous mutants of Lactococcus
      lactis IL1403 with average 6- to 11-fold-lowered sensitivities to the circular
      bacteriocin garvicin ML (GarML). Carbohydrate fermentation assays highlighted
      changes in carbohydrate metabolism, specifically loss of the ability to
      metabolize starch and maltose, in these mutants. PCR and sequencing showed that a
      13.5-kb chromosomal deletion encompassing 12 open reading frames, mainly involved
      in starch and maltose utilization, had spontaneously occurred in the GarML
      resistant mutants. Growth experiments revealed a correlation between sensitivity
      to GarML and carbon catabolite repression (CCR); i.e., sensitivity to GarML
      increased significantly when wild-type cells were grown on maltose and galactose
      as sole carbohydrates, an effect which was alleviated by the presence of glucose.
      Among the genes deleted in the mutants were malEFG, which encode a CCR-regulated
      membrane-bound maltose ABC transporter. The complementation of mutants with these
      three genes recovered normal sensitivity to the bacteriocin, suggesting an
      essential role of the maltose ABC transporter in the antimicrobial activity of
      GarML. This notion was supported by the fact that the level of sensitivity to
      GarML was dose dependent, increasing with higher expression levels of malEFG over
      a 50-fold range. To our knowledge, this is the first time a specific protein
      complex has been demonstrated to be involved in sensitivity to a circular
      bacteriocin.

PMID- 22411613
TI  - Antimicrobial-resistant strains of Clostridium difficile from North America.
AB  - A total of 316 toxigenic Clostridium difficile clinical isolates of known PCR
      ribotypes from patients in North America were screened for resistance to
      clindamycin, metronidazole, moxifloxacin, and rifampin. Clindamycin resistance
      was observed among 16 different ribotypes, with ribotypes 017, 053, and 078
      showing the highest proportions of resistance. All isolates were susceptible to
      metronidazole. Moxifloxacin resistance was present in >90% of PCR-ribotype 027
      and 053 isolates but was less common among other ribotypes. Only 7.9% of the C.
      difficile isolates were resistant to rifampin. Multidrug resistance (clindamycin,
      moxifloxacin, and rifampin) was present in 27.5% of PCR-ribotype 027 strains but
      was rare in other ribotypes. These results suggest that antimicrobial resistance
      in North American isolates of C. difficile varies by strain type and parallels
      rates of resistance reported from Europe and the Far East.

PMID- 22411614
TI  - Reduced antituberculosis drug concentrations in HIV-infected patients who are men
      or have low weight: implications for international dosing guidelines.
AB  - Reduced antituberculosis drug concentrations may contribute to unfavorable
      treatment outcomes among HIV-infected patients with more advanced immune
      suppression, and few studies have evaluated pharmacokinetics of the first-line
      antituberculosis drugs in such patients given fixed-dose combination tablets
      according to international guidelines using weight bands. In this study,
      pharmacokinetics were evaluated in 60 patients on 4 occasions during the first
      month of antituberculosis therapy. Multilevel linear mixed-effects regression
      analysis was used to examine the effects of age, sex, weight, drug dose/kilogram,
      CD4(+) lymphocyte count, treatment schedule (5 versus 7 days/week), and
      concurrent antiretrovirals (efavirenz plus lamivudine plus zidovudine) on the
      area under the concentration-time curve from 0 to 12 h (AUC(0-12)) of the
      respective antituberculosis drugs and to compare AUC(0-12)s at day 8, day 15, and
      day 29 with the day 1 AUC(0-12). Median (range) age, weight, and CD4(+)
      lymphocyte count were 32 (18 to 47) years, 55.2 (34.4 to 98.7) kg, and 252 (12 to
      500)/MUl. For every 10-kg increase in body weight, the predicted day 29 AUC(0-12)
      increased by 14.1% (95% confidence interval [CI], 7.5, 20.8), 14.1% (95% CI, 
      0.7, 31.1), 6.1% (95% CI, 2.7, 9.6) and 6.0% (95% CI, 0.8, 11.3) for rifampin,
      isoniazid, pyrazinamide, and ethambutol, respectively. Males had day 29 AUC(0
      12)s 19.3% (95% CI, 3.6, 35.1) and 14.0% (95% CI, 5.6, 22.4) lower than females
      for rifampin and pyrazinamide, respectively. Level of immune suppression and
      concomitant antiretrovirals had little effect on the concentrations of the
      antituberculosis agents. As they had reduced drug concentrations, it is important
      to review treatment responses in patients in the lower weight bands and males to
      inform future treatment guidelines, and revision of doses in these patients
      should be considered.

PMID- 22411616
TI  - The stereochemical course and mechanism of the IspH reaction.

PMID- 22411615
TI  - Further insights into the mode of action of the lipoglycopeptide telavancin
      through global gene expression studies.
AB  - Telavancin is a novel semisynthetic lipoglycopeptide derivative of vancomycin
      with a decylaminoethyl side chain that is active against Gram-positive bacteria,
      including Staphylococcus aureus strains resistant to methicillin or vancomycin. A
      dual mechanism of action has been proposed for telavancin involving inhibition of
      peptidoglycan biosynthesis and membrane depolarization. Here we report the
      results of genome-wide transcriptional profiling of the response of S. aureus to
      telavancin using microarrays. Short (15-min) challenge of S. aureus with
      telavancin revealed strong expression of the cell wall stress stimulon, a
      characteristic response to inhibition of cell wall biosynthesis. In the
      transcriptome obtained after 60-min telavancin challenge, in addition to
      induction of the cell wall stress stimulon, there was induction of various genes,
      including lrgA and lrgB, lysine biosynthesis operon (dap) genes, vraD and vraE,
      and hlgC, that have been reported to be induced by known membrane-depolarizing
      and active agents, including carbonyl cyanide m-chlorophenylhydrazone,
      daptomycin, bacitracin, and other antimicrobial peptides These genes were either
      not induced or only weakly induced by the parent molecule vancomycin. We suggest
      that expression of these genes is a response of the cell to mitigate and detoxify
      such molecules and is diagnostic of a membrane-depolarizing or membrane-active
      molecule. The results indicate that telavancin causes early and significant
      induction of the cell wall stress stimulon due to strong inhibition of
      peptidoglycan biosynthesis, with evidence in support of membrane depolarization
      and membrane activity that is expressed after a longer duration of drug
      treatment.

PMID- 22411617
TI  - Giant sigmoid diverticulum: a rare cause of common gastrointestinal symptoms.

PMID- 22411618
TI  - Use of an Endotrol endotracheal tube to facilitate orotracheal intubation with
      videolaryngoscopes.

PMID- 22411619
TI  - Responses toward a trapped animal by wild bonobos at Wamba.
AB  - Chimpanzees and bonobos are the closest living relatives of humans and diverged
      relatively recently in their phylogenetic history. However, a number of reports
      have suggested behavioral discrepancies between the two Pan species, such as more
      cooperative and tolerant social interaction and poorer tool-using repertoires in
      bonobos. Concerning hunting behavior and meat consumption, recent studies from
      the field have confirmed both behaviors not only in chimpanzees but also in
      bonobos. The present study reports an encounter by wild bonobos at Wamba with a
      duiker trapped in a snare. Bonobos interacted with the live duiker for about 10
      min but did not eventually kill the animal. They showed fear responses when the
      duiker moved and exhibited behaviors related to anxiety and stress such as branch
      drag displays and self-scratching. Although bonobos manipulated nearby saplings
      and parts of the snare, they did not use detached objects to make indirect
      contact with the duiker. Juveniles and adults of both sexes engaged in active
      interactions with the trapped duiker. Overall, bonobos' behavioral responses
      indicated species-specific cognitive characteristics largely different from those
      of chimpanzees.

PMID- 22411620
TI  - The Thatcher illusion in squirrel monkeys (Saimiri sciureus).
AB  - Like humans, Old World monkeys are known to use configural face processing to
      distinguish among individuals. The ability to recognize an individual through the
      perception of subtle differences in the configuration of facial features plays an
      important role in social cognition. To test this ability in New World monkeys,
      this study examined whether squirrel monkeys experience the Thatcher illusion, a
      measure of face processing ability in which changes in facial features are
      difficult to detect in an inverted face. In the experiment, the monkeys were
      required to distinguish between a target face and each of the three kinds of
      distracter faces whose features were altered to be different from those of the
      target. For each of the pairs of target and distracter faces, four rotation-based
      combinations of upright and inverted face presentations were used. The results
      revealed that when both faces were inverted and the eyes of the distracter face
      were altered by rotating them at an angle of 180 degrees  from those of the
      target face, the monkeys' discrimination learning was obstructed to a greater
      extent than it was under the other conditions. Thus, these results suggest that
      the squirrel monkey does experience the Thatcher illusion. Furthermore, it seems
      reasonable to assume that squirrel monkeys can utilize information about facial
      configurations in individual recognition and that this facial configuration
      information could be useful in their social communications.

PMID- 22411621
TI  - The natural compound Alizarin as an osteotropic drug for the treatment of bone
      tumors.
AB  - Despite significant clinical improvements, conventional therapies for bone cancer
      treatment are limited by significant systemic toxicity and lack of specific
      targeting. In this study, we considered Alizarin, a natural hydroxyanthraquinone
      derived from madder root with high affinity to calcium and remarkable osteotropic
      features, as a novel approach for bone cancer treatment. Due to its antitumor
      properties, as demostrated in colon cancer cells, and to its tropism to bone,
      Alizarin may be an ideal drug to reduce bone tumor growth. We demonstrated that
      low dosages of Alizarin strongly inhibited the osteosarcoma (IC(50) for Saos-2,
      MG-63, and U-2 OS cells, 27.5, 29.0, and 69.9 ug/ml, respectively) and breast
      carcinoma (IC(50) for MDA-MB-231 cells, 62.1 ug/ml) cell proliferation in vitro.
      Importantly, Alizarin had a significantly lower inhibitory activity on normal
      cells (IC(50) for MSC, 828.6 ug/ml), thereby revealing a selective activity
      towards malignant cells. Furthermore, we found that Alizarin acted through the
      inhibition of ERK phosphorylation and cell cycle arrest in the S-phase. Finally,
      Alizarin significantly and strongly impaired both osteosarcoma and breast cancer
      tumorigenesis. Our results highlight a selective and effective inhibitory
      activity of Alizarin towards cancerous cells, laying the basis for further
      studies to investigate its application in bone cancer therapy.

PMID- 22411622
TI  - Arcus venosus dorsalis pedis graft to restore the superficial palmar arch in
      devascularized hands.
AB  - For complex amputation injuries and anatomical characteristic of the metacarpus,
      restoration to the superficial palmar arch in severe devascularized or amputated
      hands remains a daunting challenge. In this article, we treated a series of five
      cases using an arcus venosus dorsalis pedis (AVDP) graft to restore the
      superficial palmar arches in devascularized hands. All hands survived and
      satisfying function was gained. The AVDP graft may be a suitable option to
      restore the superficial palmar arch in devascularized hands.

PMID- 22411623
TI  - Reconstruction of the Achilles tendon and overlying soft tissue by free composite
      anterolateral thigh flap with vascularized fascia lata.
AB  - Segmental loss of the Achilles tendon with overlying soft tissue and skin defect
      remains a complex reconstructive challenge. Successful reconstruction combines
      tendon repair with coverage of the defect by soft tissue flaps, creating an
      entity that meets up to three predetermined goals: (1) approaching preinjury
      functionality, (2) resisting shearing forces, and (3) achieving an esthetic
      result. From June 2009 to June 2011, our center submitted six patients to a one
      stage procedure correcting the Achilles tendon using a composite free
      anterolateral thigh (ALT) flap with vascularized fascia lata. The flap sizes
      ranged from 5 to 8 cm in width and 16 to 20 cm in length and all flaps included
      vascularized fascia lata which was rolled to serve as an Achilles tendon. After
      reconstruction our patients showed good functional results, these patients could
      walk, climb stairs, and tiptoe again without support. Moreover, normal footwear
      could be worn. A free composite ALT flap with vascularized fascia lata is a
      reliable option for coverage of Achilles tendon and overlying soft tissue
      defects, even in elderly patients.

PMID- 22411624
TI  - Prevention of ulceration, amputation, and reduction of hospitalization: outcomes
      of a prospective multicenter trial of tibial neurolysis in patients with diabetic
      neuropathy.
AB  - This is the first multicenter prospective study of outcomes of tibial neurolysis
      in diabetics with neuropathy and chronic compression of the tibial nerve in the
      tarsal tunnels. A total of 38 surgeons enrolled 628 patients using the same
      technique for diagnosis of compression, neurolysis of four medial ankle tunnels,
      and objective outcomes: ulceration, amputation, and hospitalization for foot
      infection. Contralateral limb tibial neurolysis occurred in 211 patients for a
      total of 839 operated limbs. Kaplan-Meier proportional hazards were used for
      analysis. New ulcerations occurred in 2 (0.2%) of 782 patients with no previous
      ulceration history, recurrent ulcerations in 2 (3.8%) of 57 patients with a
      previous ulcer history, and amputations in 1 (0.2%) of 839 at risk limbs.
      Admission to the hospital for foot infections was 0.6%. In patients with diabetic
      neuropathy and chronic tibial nerve compression, neurolysis can result in
      prevention of ulceration and amputation, and decrease in hospitalization for foot
      infection.

PMID- 22411625
TI  - A positive Tinel sign as predictor of pain relief or sensory recovery after
      decompression of chronic tibial nerve compression in patients with diabetic
      neuropathy.
AB  - Predictive ability of a positive Tinel sign over the tibial nerve in the tarsal
      was evaluated as a prognostic sign in determining sensory outcomes after distal
      tibial neurolysis in diabetics with chronic nerve compression at this location.
      Outcomes were evaluated with a visual analog score (VAS) for pain and
      measurements of the cutaneous pressure threshold/two-point discrimination. A
      multicenter prospective study enrolled 628 patients who had a positive Tinel
      sign. Of these patients, 465 (74%) had VAS >5. Each patient had a release of the
      tarsal tunnel and a neurolysis of the medial and lateral plantar and calcaneal
      tunnels. Subsequent, contralateral, identical surgery was done in 211 of the
      patients (152 of which had a VAS >5). Mean VAS score decreased from 8.5 to 2.0 (p
      <0.001) at 6 months, and remained at this level for 3.5 years. Sensibility
      improved from a loss of protective sensation to recovery of some two-point
      discrimination during this same time period. It is concluded that a positive
      Tinel sign over the tibial nerve at the tarsal tunnel in a diabetic patient with
      chronic nerve compression at this location predicts significant relief of pain
      and improvement in plantar sensibility.

PMID- 22411626
TI  - Imaging isolated gold atom catalytic sites in zeolite NaY.

PMID- 22411628
TI  - ADAP regulates cell cycle progression of T cells via control of cyclin E and Cdk2
      expression through two distinct CARMA1-dependent signaling pathways.
AB  - Adhesion and degranulation-promoting adapter protein (ADAP) is a multifunctional
      scaffold that regulates T cell receptor-mediated activation of integrins via
      association with the SKAP55 adapter and the NF-kappaB pathway through
      interactions with both the CARMA1 adapter and serine/threonine kinase
      transforming growth factor beta-activated kinase 1 (TAK1). ADAP-deficient T cells
      exhibit impaired proliferation following T cell receptor stimulation, but the
      contribution of these distinct functions of ADAP to this defect is not known. We
      demonstrate that loss of ADAP results in a G1-S transition block in cell cycle
      progression following T cell activation due to impaired accumulation of cyclin
      dependent kinase 2 (Cdk2) and cyclin E. The CARMA1-binding site in ADAP is
      critical for mitogen-activated protein (MAP) kinase kinase 7 (MKK7)
      phosphorylation and recruitment to the protein kinase C theta (PKCtheta)
      signalosome and subsequent c-Jun kinase (JNK)-mediated Cdk2 induction. Cyclin E
      expression following T cell receptor stimulation of ADAP-deficient T cells is
      transient and associated with enhanced cyclin E ubiquitination. Both the CARMA1-
      and TAK1-binding sites in ADAP are critical for restraining cyclin E
      ubiquitination and turnover independently of ADAP-dependent JNK activation. T
      cell receptor-mediated proliferation was most dramatically impaired by the loss
      of ADAP interactions with CARMA1 or TAK1 rather than SKAP55. Thus, ADAP
      coordinates distinct CARMA1-dependent control of key cell cycle proteins in T
      cells.

PMID- 22411627
TI  - Reactive oxygen species and epidermal growth factor are antagonistic cues
      controlling SHP-2 dimerization.
AB  - The SHP-2 tyrosine phosphatase plays key regulatory roles in the modulation of
      the cell response to growth factors and cytokines. Over the past decade, the
      integration of genetic, biochemical, and structural data has helped in
      interpreting the pathological consequences of altered SHP-2 function. Using
      complementary approaches, we provide evidence here that endogenous SHP-2 can
      dimerize through the formation of disulfide bonds that may also involve the
      catalytic cysteine. We show that the fraction of dimeric SHP-2 is modulated by
      growth factor stimulation and by the cell redox state. Comparison of the
      phosphatase activities of the monomeric self-inhibited and dimeric forms
      indicated that the latter is 3-fold less active, thus pointing to the
      dimerization process as an additional mechanism for controlling SHP-2 activity.
      Remarkably, dimers formed by different SHP-2 mutants displaying diverse
      biochemical properties were found to respond differently to epidermal growth
      factor (EGF) stimulation. Although this differential behavior cannot be
      rationalized mechanistically yet, these findings suggest a possible regulatory
      role of dimerization in SHP-2 function.

PMID- 22411629
TI  - The general transcription factor TAF7 is essential for embryonic development but
      not essential for the survival or differentiation of mature T cells.
AB  - TAF7, a component of the TFIID complex that nucleates the assembly of
      transcription preinitiation complexes, also independently interacts with and
      regulates the enzymatic activities of other transcription factors, including P
      TEFb, TFIIH, and CIITA, ensuring an orderly progression in transcription
      initiation. Since not all TAFs are required in terminally differentiated cells,
      we examined the essentiality of TAF7 in cells at different developmental stages
      in vivo. Germ line disruption of the TAF7 gene is embryonic lethal between 3.5
      and 5.5 days postcoitus. Mouse embryonic fibroblasts with TAF7 deleted cease
      transcription globally and stop proliferating. In contrast, whereas TAF7 is
      essential for the differentiation and proliferation of immature thymocytes, it is
      not required for subsequent, proliferation-independent differentiation of lineage
      committed thymocytes or for their egress into the periphery. TAF7 deletion in
      peripheral CD4 T cells affects only a small number of transcripts. However, T
      cells with TAF7 deleted are not able to undergo activation and expansion in
      response to antigenic stimuli. These findings suggest that TAF7 is essential for
      proliferation but not for proliferation-independent differentiation.

PMID- 22411630
TI  - Vancomycin-induced nephrotoxicity: mechanism, incidence, risk factors and special
      populations. A literature review.
AB  - PURPOSE: Treatment failures following vancomycin therapy in patients with
      methicillin-resistant Staphylococcus aureus infections have led to the
      utilization of higher doses of this antibiotic to achieve the trough
      concentrations of 10-20 MUg/mL recommended by the Infectious Diseases Society of
      America clinical practice guideline. However, many questions remain on the safety
      of such high doses of vancomycin, specifically their nephrotoxic effects. In this
      review, we have collected available evidence on the nephrotoxicity of vancomycin,
      particularly in terms of its mechanism, incidence, predisposing factors and
      special target populations. METHOD: The data were collected by searching Scopus,
      PubMed, Medline, and Cochrane database systematic reviews. The key words used as
      search terms were "vancomycin", "nephrotoxicity", "renal failure", "renal
      damage", "risk factors", "infants", "children", "adult", "elderly" and
      "pregnancy". We have included all relevant animal and human studies up to the
      date of publication. RESULTS AND CONCLUSION: Vancomycin-induced renal toxicity
      was reported in 10-20 % and 30-40 % of patients following conventional and high
      doses of vancomycin therapy, respectively .The most probable mechanism for its
      nephrotoxicity can be at least partially attributable to an increased production
      of reactive oxygen species and oxidative stress. There are a number of different
      risk factors which could accelerate or potentiate the occurrence of vancomycin
      induced nephrotoxicity, with the most documented risk factors being high trough
      vancomycin level (especially >20 mg/L) or doses (>4 g/day), concomitant treatment
      with nephrotoxic agents, prolonged therapy (even more than 7 days), and
      admittance to an intensive care unit (especially prolonged stay). It is necessary
      to carry out more studies, especially those focused on the association between
      nephrotoxicity and high trough levels of vancomycin.

PMID- 22411631
TI  - Induction of interleukin-8 by Naegleria fowleri lysates requires activation of
      extracellular signal-regulated kinase in human astroglial cells.
AB  - Naegleria fowleri is a pathogenic free-living amoeba which causes primary amoebic
      meningoencephalitis in humans and experimental animals. To investigate the
      mechanisms of such inflammatory diseases, potential chemokine gene activation in
      human astroglial cells was investigated following treatment with N. fowleri
      lysates. We demonstrated that N. fowleri are potent inducers for the expression
      of interleukin-8 (IL-8) genes in human astroglial cells which was preceded by
      activation of extracellular signal-regulated kinase (ERK). In addition, N.
      fowleri lysates induces the DNA binding activity of activator protein-1 (AP-1),
      an important transcription factor for IL-8 induction. The specific mitogen
      activated protein kinase kinase/ERK inhibitor, U0126, blocks N. fowleri-mediated
      AP-1 activation and subsequent IL-8 induction. N. fowleri-induced IL-8 expression
      requires activation of ERK in human astroglial cells. These findings indicate
      that treatment of N. fowleri on human astroglial cells leads to the activation of
      AP-1 and subsequent expression of IL-8 which are dependent on ERK activation.
      These results may help understand the N. fowleri-mediated upregulation of
      chemokine and cytokine expression in the astroglial cells.

PMID- 22411632
TI  - Identification of microorganisms in partially fed female horn flies, Haematobia
      irritans.
AB  - The horn fly Haematobia irritans (Linnaeus, 1758) (Diptera: Muscidae) is one of
      the most important ectoparasites of cattle. The parasitism of horn flies
      interferes with cattle feeding, thus reducing weight gain and milk production.
      Additionally, horn flies are mechanical vectors of pathogens that cause disease
      in cattle. The aims of this study were to identify microorganisms in partially
      fed female horn flies through mining of expressed sequence tags (ESTs) and to
      characterize microorganism prevalence using real-time RT-PCR. Seven unigenes
      containing 24 ESTs were homologous to infectious agents. Microorganisms
      identified in partially fed female horn flies ESTs included Nora virus (3
      unigenes; 8 ESTs), Wolbachia endosymbionts (3 unigenes; 3 ESTs), and
      Mycobacterium bovis (1 unigene; 13 ESTs). These results expanded the repertoire
      of microorganisms that could cause persistent infections or be mechanically
      transmitted by horn flies and support further studies on the role of horn flies
      in the epidemiology of these pathogens in Mexico.

PMID- 22411633
TI  - Comparison between the collagen intensity and mast cell density in the lingual
      muscles and myocardium of autopsied chronic chagasic and nonchagasic patients.
AB  - In chronic Chagas' disease (CD), an increase in collagen intensity and mast cell
      density has been described individually in the myocardium and tongue muscles. The
      aim of this study was to compare the percentage of collagen, mast cell tryptase
      (MCT) density, and mast cell chymase (MCH) density in the lingual muscles and
      myocardium from autopsied chagasic (CP) and nonchagasic patients (NCP). The
      selected cases were divided into two groups: (1) CP (n = 10) and (2) NCP (n =
      10). Fragments were removed from the tongue and heart. After histological
      processing, the slices were stained with picrosirius, and immunohistochemistry
      was performed for MCH and MCT. The CP group showed the highest MCH and MCT
      densities and the highest percentage of collagen in the lingual muscles and
      myocardium when compared with the NCP group (p < 0.05). A significant positive
      correlation was observed between the collagen intensity and MCH density in the
      myocardium of the CP group. Although there are no reports in the literature of
      MCT and MCH in CD, its higher densities as well as higher percentage of collagen
      were found in the lingual muscles and myocardium in the CP group, suggesting that
      tryptase and chymase are associated with the pathogenesis of CD in these organs.
      Furthermore, the positive and significant correlation between the percentage of
      collagen and MCH density in the myocardium of the CP group suggests that the
      chymase is associated with fibrosis in CD, as demonstrated in other diseases.

PMID- 22411634
TI  - From methylene blue to chloroquine: a brief review of the development of an
      antimalarial therapy.
AB  - Malarial treatment is widely and readily available today. However, there was a
      time in the not-so-distant past when malaria was a deadly disease with no known
      cause or cure. In this article, we trace the origins of an antimalarial therapy
      from the discovery of the nature of the malarial parasite through the development
      of chloroquine. We dedicate this article to Johann "Hans" Andersag, the scientist
      who developed chloroquine, on the 110th anniversary of his birth, 16 February
      1902.

PMID- 22411635
TI  - The potential role of Phoenix dactylifera on Eimeria papillata-induced infection
      in mice.
AB  - Coccidiosis is a common infectious disease in poultry causing major economic
      losses. Here, we investigated the effect of Khodary date fruit aqueous extract (4
      ml/kg) on the outcome of coccidiosis caused by Eimeria papillata in Swiss Albino
      mice. Date fruit extract was able to decrease the intracellular development by
      lowering the faecal output of E. papillata oocysts from 8.7 +/- 0.5 * 10(3) to
      6.6 +/- 0.4 * 10(3) oocysts per gram faeces. Also, date extract caused a great
      diminish in body weight of infected mice from 19.3 to 3.2 %. The number of
      parasitic stages in the intestinal villi of the infected mice was reduced to
      about 52 % after treatment with date extract. The infection was associated with
      marked histopathological lesions of the murine jejunum in the form of
      inflammation, vacuolation of the epithelium, and destruction of some villi. Also,
      the number of goblet cells within the infected villi was significantly lowered (P
      <= 0.05). These changes lead to an oxidative damage of the infected tissue.
      Moreover, infection induced a disturbance in both protein and carbohydrate
      content in the infected mice. Treatment of mice with date extract could improve
      the above-studied parameters. On the basis of the above results it can be
      hypothesized that date fruit can protect against coccidiosis-induced infection,
      this hypothesis can be revealed by the anti-inflammatory activity of date
      protecting host tissue from injuries induced by the parasite, and hence it is
      recommended to be used as an excellent food additive.

PMID- 22411636
TI  - Comparative modeling and protein-like features of hydrophobic-polar models on a
      two-dimensional lattice.
AB  - Lattice models of proteins have been extensively used to study protein
      thermodynamics, folding dynamics, and evolution. Our study considers two
      different hydrophobic-polar (HP) models on the 2D square lattice: the purely HP
      model and a model where a compactness-favoring term is added. We exhaustively
      enumerate all the possible structures in our models and perform the study of
      their corresponding folds, HP arrangements in space and shapes. The two models
      considered differ greatly in their numbers of structures, folds, arrangements,
      and shapes. Despite their differences, both lattice models have distinctive
      protein-like features: (1) Shapes are compact in both models, especially when a
      compactness-favoring energy term is added. (2) The residue composition is
      independent of the chain length and is very close to 50% hydrophobic in both
      models, as we observe in real proteins. (3) Comparative modeling works well in
      both models, particularly in the more compact one. The fact that our models show
      protein-like features suggests that lattice models incorporate the fundamental
      physical principles of proteins. Our study supports the use of lattice models to
      study questions about proteins that require exactness and extensive calculations,
      such as protein design and evolution, which are often too complex and
      computationally demanding to be addressed with more detailed models.

PMID- 22411637
TI  - Efficient delivery of antitumor drug to the nuclei of tumor cells by amphiphilic
      biodegradable poly(L-aspartic acid-co-lactic acid)/DPPE co-polymer nanoparticles.
AB  - The use of biodegradable polymeric nanoparticles (NPs) for controlled drug
      delivery has shown significant therapeutic potential. Polyaspartic acid and
      polylactic acid are the most intensively studied biodegradable polymers. In the
      present study, novel amphiphilic biodegradable co-polymer NPs, poly(L-aspartic
      acid-co-lactic acid) with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE)
      (poly(AA-co-LA)/DPPE) is synthesized and subsequently used to encapsulate an
      antitumor drug doxorubicin (DOX). The formulation parameters of the NPs are
      optimized to improve encapsulation efficiency. The resulting drug-loaded NPs
      possess better size homogeneity (polydispersity) and exhibit pH-responsive drug
      release profiles. Cellular viability assays indicate that the poly(AA-co-LA)/DPPE
      NPs did not induce cell death, whereas doxorubicin encapsulated NPs were
      cytotoxic to various types of tumor cells. In addition, the free NPs could not
      enter the cell nuclei after internalized in tumor cells. The DOX-loaded NPs
      exhibit efficient intracellular delivery in tumor cells with co-localization in
      lysosome and delay entering into the nucleus, which suggests a time- and pH
      dependent drug release profile within cells. When applied to deliver
      chemotherapeutics to a mouse xenograft model of human lung adenocarcinoma, DOX
      loaded NPs have a comparable antitumor activity with free DOX, and greatly reduce
      systemic toxicity and mortality. The delivery of cytotoxic drugs directly to the
      nucleus specifically within tumor cells is of great interest. These results
      demonstrate the feasibility of the application of the amphiphilic polyaspartic
      acid derivative, poly(AA-co-LA)/DPPE, as a nanocarrier for cell nuclear delivery
      of potent antitumor drugs.

PMID- 22411640
TI  - Quality and innovation in the NHS.

PMID- 22411641
TI  - Improving the life expectancy of people with serious mental illness.

PMID- 22411638
TI  - Fibroblast growth factor and bone morphogenetic protein signaling are required
      for specifying prechondrogenic identity in neural crest-derived mesenchyme and
      initiating the chondrogenic program.
AB  - The pharyngeal endoderm is hypothesized as the source of local signals that
      specify the identity of neural crest-derived mesenchyme in the arches. Sox9 is
      induced and maintained in prechondrogenic cells during condensation formation and
      endochondral ossification. Using explant culture, we determined that pharyngeal
      endoderm was sufficient, but not necessary for specifying prechondrogenic
      identity, as surrounding tissues including the otic vesicle can compensate for
      signals from the pharyngeal endoderm. Multiple Fgf genes are expressed
      specifically in the pharyngeal endoderm subjacent to the neural crest-derived
      mesenchyme. Fibroblast growth factor (FGF) signaling is both sufficient and
      required for specification of Sox9 expression and specification of
      prechondrogenic identity, as demonstrated by the addition of recombinant FGF
      protein or the FGF receptor inhibitor (SU5402) to explanted tissue, respectively.
      However, FGF signaling cannot maintain Sox9 expression or initiate the
      chondrogenic program as indicated by the absence of Col2a1 transcripts. Bone
      morphogenetic protein (BMP) 4 signaling can induce and maintain Sox9 expression
      in isolated mesenchyme, but only in combination with FGF signaling induce Col2a1
      expression, and thus, chondrogenesis. Given the spatiotemporal expression
      patterns of FGFs and BMPs in the pharyngeal arches, we suggest that this may
      represent a general mechanism of local signals specifying prechondrogenic
      identity and initiation of the chondrogenic program.

PMID- 22411639
TI  - The safety and efficacy of intravenous ketorolac in patients undergoing primary
      endoscopic sinus surgery: a randomized, double-blinded clinical trial.
AB  - BACKGROUND: Ketorolac (KT) is an intravenous (IV) nonsteroidal anti-inflammatory
      drug (NSAID) for acute, moderate pain. KT is safe, but may be linked to increased
      risk of post-tonsillectomy hemorrhage. The safety and efficacy of KT following
      primary endoscopic sinus surgery (ESS) is unknown. METHODS: All patients
      underwent primary ESS and septoplasty. Patients randomly received either IVKT 30
      mg or IV fentanyl (IVF) 25 MUg postprocedure. Postoperative pain was recorded at
      0, 30, and 60 minutes via visual analog scale (VAS), and patients received as
      needed fentanyl and hydrocodone/acetaminophen for additional pain. Postoperative
      bleeding questionnaires were completed on postoperative days 1 and 7 (POD 1 and
      POD 7). Preoperative and POD 7 hemoglobin was assessed. RESULTS: A total of 34
      patients enrolled in the study over 1 year. Sixteen patients received IVKT and 18
      patients received IVF. The average time of administration was 23 +/- 6 minutes
      postprocedure. There were no significant differences in preoperative and
      postoperative hemoglobin levels between groups and bleeding assessments. There
      were no incidences of postoperative hemorrhage. There was no significant
      difference in pain VAS between the IVKT and IVF groups (3.5, 3.2, 2.1 vs 3.0,
      4.4, 3.8 at 0, 30, and 60 minutes, respectively). There was no significant
      difference between the number of doses of supplemental analgesics for the IVKT
      and IVF groups (2.0 vs 3.4 doses IV; 1.0 vs 1.4 doses orally, respectively).
      CONCLUSION: In this study, IVKT was a safe analgesic in the setting of primary
      ESS. There was no increased risk of hemorrhage or acute blood-loss anemia. IVKT
      did not appear to offer statistically significant pain control over IVF.

PMID- 22411642
TI  - Pharmacokinetic interactions between antiretroviral drugs and herbal medicines.

PMID- 22411643
TI  - Common prescribing errors  in renal patients.

PMID- 22411644
TI  - Role of tapentadol in pain management.

PMID- 22411645
TI  - Diagnosis and treatment of hereditary angio-oedema attacks.

PMID- 22411646
TI  - Will telemedicine facilitate access to hyper acute stroke care across the UK?

PMID- 22411647
TI  - Inherited arrhythmia syndromes.

PMID- 22411648
TI  - Sophia Jex-Blake: the first woman medical graduate to practise in the UK.

PMID- 22411649
TI  - Acute splenic sequestration crisis  in an adult with sickle cell anaemia.

PMID- 22411650
TI  - Autonomic failure following deep brain stimulation for Parkinson's disease.

PMID- 22411651
TI  - Vancomycin-induced cutaneous vasculitis.

PMID- 22411652
TI  - Lofgren's syndrome.

PMID- 22411653
TI  - Visceral heterotaxy and malrotation in a neonate.

PMID- 22411655
TI  - Using a will to plan ahead.

PMID- 22411654
TI  - Nasal septal haematoma: a post-traumatic complication.

PMID- 22411657
TI  - Optimal analgesia for laparoscopic colorectal surgery in an enhanced recovery
      programme.

PMID- 22411658
TI  - Predictability of intraocular lens calculation and early refractive status: the
      Infant Aphakia Treatment Study.
AB  - OBJECTIVE: To report the accuracy of intraocular lens (IOL) power calculations
      and the early refractive status in pseudophakic eyes of infants in the Infant
      Aphakia Treatment Study. METHODS: Eyes randomized to receive primary IOL
      implantation were targeted for a postoperative refraction of +8.0 diopters (D)
      for infants 28 to 48 days old at surgery and +6.0 D for those 49 days or older to
      younger than 7 months at surgery using the Holladay 1 formula. Refraction 1 month
      after surgery was converted to spherical equivalent, and prediction error (PE;
      defined as the calculated refraction minus the actual refraction) and absolute PE
      were calculated. Baseline eye and surgery characteristics and A-scan quality were
      analyzed to compare their effect on PE. MAIN OUTCOME MEASURES: Prediction error.
      RESULTS: Fifty-six eyes underwent primary IOL implantation; 7 were excluded for
      lack of postoperative refraction (n = 5) or incorrect technique in refraction (n
      = 1) or biometry (n = 1). Overall mean (SD) absolute PE was 1.8 (1.3) D and mean
      (SD) PE was +1.0 (2.0) D. Absolute PE was less than 1 D in 41% of eyes but
      greater than 2 D in 41% of eyes. Mean IOL power implanted was 29.9 D (range, 11.5
      40.0 D); most eyes (88%) implanted with an IOL of 30.0 D or greater had less
      postoperative hyperopia than planned. Multivariate analysis revealed that only
      short axial length (<18 mm) was significant for higher PE. CONCLUSIONS: Short
      axial length correlates with higher PE after IOL placement in infants. Less
      hyperopia than anticipated occurs with axial lengths of less than 18 mm or high
      power IOLs. Application to Clinical Practice Quality A-scans are essential and
      higher PE is common, with a tendency for less hyperopia than expected. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00212134.

PMID- 22411659
TI  - Influence of parental health literacy and dosing responsibility on pediatric
      glaucoma medication adherence.
AB  - OBJECTIVE: To assess glaucoma medication adherence in children, hypothesizing
      that poor parental health literacy and eye drop instillation by the child are
      associated with worse adherence. METHODS: This prospective, observational study
      enrolled pediatric patients with glaucoma who were prescribed eye drops.
      Parent(s) reported who was responsible for eye drop instillation (parent vs
      child), took the Rapid Estimate of Adult Literacy in Medicine, and were
      instructed on the use and purpose of the Medication Event Monitoring System.
      Calculations included average adherence (proportion of prescribed doses taken),
      dosing errors (number of overdosing or underdosing events in 24 hours), and
      proportion of doses taken on schedule (doses taken within 2 hours of prescribed
      dosing interval). Results are reported as mean (SD) or median. RESULTS: The study
      included 46 of the 50 enrolled children who used the Medication Event Monitoring
      System for 30 days or more. Adherence ranged from 43% to 107% (93% [12%]) and was
      not associated with age (slope, 0.09 [0.52]; P = .86) but decreased with the
      parent's lower health literacy (slope, 0.62 [0.24]; P = .01).The mean number of
      dosing errors for medications prescribed daily vs twice daily was similar (3.3 vs
      2.9; P = .66). The proportion of doses taken on schedule (within 2 hours of
      prescribed dosing interval) ranged from 3% to 97% (median, 34%; mean, 41% [24%])
      and was better when the parent vs the child instilled eye drops (46% [26%] vs 23%
      [19%]; P < .001). CONCLUSIONS: Time-dependent glaucoma medication adherence was
      better when the parent was responsible for eye drop instillation. Overall
      decreased adherence was associated with decreased parental health literacy.
      Children of parents with poor health literacy are vulnerable to poor medication
      adherence; efforts to address poor health literacy may improve outcomes.

PMID- 22411661
TI  - Thyroid-associated periorbitopathy: eyebrow fat and soft tissue expansion in
      patients with thyroid-associated orbitopathy.
AB  - OBJECTIVE: To compare soft tissue and fat volumes in the supraorbital area of
      healthy patients and patients with thyroid-associated orbitopathy (TAO) using 3
      dimensional reconstruction software. METHODS: The superiolateral orbital area was
      delineated on a bony framework. Three-dimensional reconstruction and volumetric
      calculation of the retro-orbicularis oculi fat (brow fat), galeal fat (including
      the retro-orbicularis oculi fat), and soft-tissue muscle were performed. RESULTS:
      We analyzed 100 computed tomographic scans from 48 patients with TAO and 52
      control subjects. All patients showed an age-related increase of fat volumes. The
      mean total eyebrow volume was greater in patients with TAO vs healthy control
      subjects (P < .001). Galeal fat (P = .02) and retro-orbicularis oculi fat (P =
      .01) volumes were significantly higher in patients with TAO vs control subjects.
      Soft-tissue muscle volume decreased with age in healthy females but remained
      constant in the aging female group with TAO. Both total volume and brow thickness
      did not appear to change with age in healthy patients but exhibited an increase
      in the female population with TAO. CONCLUSIONS: This study brings into focus the
      clinicopathologic entity of thyroid-associated periorbitopathy. Three-dimensional
      evaluation of computed tomographic scans can provide information on volumetric
      changes in the eyebrow profile of patients with TAO. Further investigation of the
      biologic and morphologic changes of eyebrow fat and soft tissue in patients with
      TAO may help better characterize, classify, and guide their treatment.

PMID- 22411660
TI  - Effect of race, age, and axial length on optic nerve head parameters and retinal
      nerve fiber layer thickness measured by Cirrus HD-OCT.
AB  - OBJECTIVE: To determine the effect of race, demographic, and ocular variables on
      optic nerve head and retinal nerve fiber layer (RNFL) thickness measurements
      using spectral-domain optical coherence tomography. METHODS: In a cross-sectional
      observational study, 284 normal subjects aged 18 to 84 years were evaluated at 7
      sites using Cirrus HD-OCT. Disc area, rim area, average cup-disc ratio, vertical
      cup-disc ratio, cup volume, and average, temporal, superior, nasal, and inferior
      RNFL thicknesses were calculated. The main outcome measures were associations
      between Cirrus HD-OCT optic nerve head and RNFL measurements and age, sex, and
      race. RESULTS: The 284 subjects self-identified as being of European (122),
      Chinese (63), African (51), or Hispanic (35) descent. After adjusting for the
      effect of age, there was a statistically significant difference among racial
      groups for all optic nerve head and RNFL parameters (all P <= .005) except rim
      area (P = .22). Rim area, average cup-disc ratio, vertical cup-disc ratio, and
      cup volume were moderately associated with disc area (r(2) = 0.15, 0.33, 0.33,
      and 0.37, respectively). After a linear adjustment for disc area, there was no
      statistically significant difference among racial groups for any optic nerve head
      parameter. Individuals of European descent had thinner RNFL measurements except
      in the temporal quadrant. CONCLUSIONS: There are racial differences in optic disc
      area, average cup-disc ratio, vertical cup-disc ratio, cup volume, and RNFL
      thickness as measured by Cirrus HD-OCT. These differences should be considered
      when using Cirrus HD-OCT to assess for glaucomatous damage in differing
      population groups.

PMID- 22411662
TI  - Visual impairment, uncorrected refractive error, and accelerometer-defined
      physical activity in the United States.
AB  - OBJECTIVE: To examine how accelerometer-measured physical activity is affected by
      visual impairment (VI) and uncorrected refractive error (URE). DESIGN: Cross
      sectional study using data from the 2003-2004/2005-2006 National Health and
      Nutritional Examination Survey. Visual impairment was defined as better-eye
      postrefraction visual acuity worse than 20/40. Uncorrected refractive error was
      defined as better-eye presenting visual acuity of 20/50 or worse, improving to
      20/40 or better with refraction. Adults older than 20 years with normal sight,
      URE, and VI were analyzed. The main outcome measures were steps per day and daily
      minutes of moderate or vigorous physical activity (MVPA). RESULTS: Five thousand
      seven hundred twenty-two participants (57.1%) had complete visual acuity and
      accelerometer data. Individuals with normal sight took an average of 9964 steps
      per day and engaged in an average of 23.5 minutes per day of MVPA, as compared
      with 9742 steps per day and 23.1 minutes per day of MVPA in individuals with URE
      (P > .50 for both) and 5992 steps per day and 9.3 minutes/d of MVPA in
      individuals with VI (P < .01 for both). In multivariable models, individuals with
      VI took 26% fewer steps per day (P < .01; 95% CI, 18%-34%) and spent 48% less
      time in MVPA (P < .01; 95% CI, 37%-57%) than individuals with normal sight. The
      decrement in steps and MVPA associated with VI equaled or exceeded that
      associated with self-reported chronic obstructive pulmonary disease, diabetes
      mellitus, arthritis, stroke, or congestive heart failure. CONCLUSIONS: Visual
      impairment, but not URE, impacts physical activity equal to or greater than other
      serious medical conditions. The substantial decrement in physical activity
      observed in nonrefractive vision loss highlights a need for better strategies to
      safely improve mobility and increase physical activity in this group.

PMID- 22411663
TI  - Suppression of thrombospondin-1 expression during uveal melanoma progression and
      its potential therapeutic utility.
AB  - OBJECTIVES: To determine whether expression of thrombospondin-1 (TSP1), an
      endogenous inhibitor of angiogenesis, is downregulated during progression of
      uveal melanoma and whether administration of TSP1 and/or its antiangiogenic
      peptides attenuate tumor growth. METHODS: Tyrosinase-SV40 T-antigens (Tyr Tag)
      transgenic mice were used for evaluation of TSP1 expression during tumor
      progression using immunohistological methods. The therapeutic potential of TSP1
      on tumor progression was evaluated either by crossing Tyr Tag mice with a line of
      transgenic mice overexpressing TSP1 in the eye or by administration of TSP1
      mimetic peptide with known antiangiogenic, antitumor activity. Tumor areas were
      measured in histological sections using Optima software (Media Cybernetics, Inc).
      RESULTS: The Tyr Tag tumors from 3-week-old mice showed significant TSP1
      expression, which was dramatically downregulated in tumors from 12-week-old mice.
      Furthermore, the development and progression of tumor was significantly delayed
      in Tyr Tag TSP1 transgenic mice or Tyr Tag mice receiving TSP1-mimetic peptide
      (100 mg/kg/d). CONCLUSIONS: Expression of TSP1 was decreased with the angiogenic
      switch during progression of uveal melanoma, and TSP1 and/or its antiangiogenic
      peptides were effective in attenuation of tumor growth. CLINICAL RELEVANCE:
      Modulation of TSP1 expression and/or activity may be beneficial in treating uveal
      melanoma.

PMID- 22411664
TI  - Extraocular muscles in patients with infantile nystagmus: adaptations at the
      effector level.
AB  - OBJECTIVE: To test the hypothesis that the extraocular muscles (EOMs) of patients
      with infantile nystagmus have muscular and innervational adaptations that may
      have a role in the involuntary oscillations of the eyes. METHODS: Specimens of
      EOMs from 10 patients with infantile nystagmus and postmortem specimens from 10
      control subjects were prepared for histologic examination. The following
      variables were quantified: mean myofiber cross-sectional area, myofiber central
      nucleation, myelinated nerve density, nerve fiber density, and neuromuscular
      junction density. RESULTS: In contrast to control EOMs, infantile nystagmus EOMs
      had significantly more centrally nucleated myofibers, consistent with cycles of
      degeneration and regeneration. The EOMs of patients with nystagmus also had a
      greater degree of heterogeneity in myofiber size than did those of controls, with
      no difference in mean myofiber cross-sectional area. Mean myelinated nerve
      density, nerve fiber density, and neuromuscular junction density were also
      significantly decreased in infantile nystagmus EOMs. CONCLUSIONS: The EOMs of
      patients with infantile nystagmus displayed a distinct hypoinnervated phenotype.
      This represents the first quantification of changes in central nucleation and
      myofiber size heterogeneity, as well as decreased myelinated nerve, nerve fiber,
      and neuromuscular junction density. These results suggest that deficits in motor
      innervation are a potential basis for the primary loss of motor control. CLINICAL
      RELEVANCE: Improved understanding of the etiology of nystagmus may direct future
      diagnostic and treatment strategies.

PMID- 22411666
TI  - Vincent (Censu) Tabone, an ophthalmologist and a president of the Republic of
      Malta.
AB  - Vincent Tabone may be unique in the history of ophthalmology. He practiced
      ophthalmology for 40 years in his homeland, the Republic of Malta. During that
      time, he became well known as a pioneer in the international effort to eradicate
      trachoma worldwide. At age 53, he began a long and successful political career as
      a member of parliament, then as a cabinet minister, and, finally, as the
      democratically elected president of the Republic. He was active in European
      diplomacy and made important contributions at the United Nations. He may be the
      only ophthalmologist who has made great contributions in the field of medicine
      and in the democratic development of his country.

PMID- 22411665
TI  - Projected clinical outcomes of glaucoma screening in African American
      individuals.
AB  - OBJECTIVES: To project the clinical impact of routine glaucoma screening on
      visual outcomes in middle-aged African American individuals and help guide
      glaucoma screening policy. METHODS: Using data from the Eye Diseases Prevalence
      Research Group and Baltimore Eye Study, we developed a microsimulation model to
      project visual outcomes in African American individuals screened for glaucoma
      under a national screening policy using frequency-doubling technology. We
      projected the impact of universal screening on glaucoma-related visual impairment
      (acuity worse than 20/40 but better than 20/200 in the better-seeing eye) and
      blindness (acuity 20/200 or worse in the better-seeing eye). The diagnostic
      characteristics of frequency-doubling technology and the hazard ratio for
      glaucoma progression in treated patients were informed by meta-analyses of
      randomized controlled trials. RESULTS: Implementation of a national glaucoma
      screening policy for a cohort of African American individuals between the ages of
      50 and 59 years without known glaucoma would reduce the lifetime prevalence of
      undiagnosed glaucoma from 50% to 27%, the prevalence of glaucoma-related visual
      impairment from 4.6% to 4.4% (4.1% relative decrease), and the prevalence of
      glaucoma-related blindness from 6.1% to 5.6% (7.1% relative decrease). We project
      the cost of the program to be $80 per screened individual, considering only the
      cost of frequency-doubling technology and confirmatory eye examinations. The
      number needed to screen to diagnose 1 person with glaucoma is 58. The number
      needed to screen to prevent 1 person from developing visual impairment is 875.
      CONCLUSIONS: Routine glaucoma screening for middle-aged African American
      individuals is potentially clinically effective but its impact on visual
      impairment and blindness may be modest. However, we did not assess the impact on
      visual field loss.

PMID- 22411667
TI  - Thyroid-associated periorbitopathy: of mountains, measurements, and levels of
      evidence.

PMID- 22411668
TI  - Intravitreal corticosteroid therapy: putting the problem of glaucoma in
      perspective.

PMID- 22411669
TI  - Fluorescein angiographic and histopathologic findings of bilateral peripheral
      retinal nonperfusion in nonaccidental injury: a case series.

PMID- 22411670
TI  - Retinal pigment epithelial depigmented lesions associated with tuberous sclerosis
      complex.

PMID- 22411671
TI  - Eyelid bee sting with late migration onto the cornea after primary removal: the
      mystery of the bee stinger.

PMID- 22411672
TI  - Percentage of fellow eyes that develop full-thickness macular hole in patients
      with unilateral macular hole.

PMID- 22411673
TI  - Reversal of poliosis and vitiligo following Vogt-Koyanagi-Harada disease.

PMID- 22411674
TI  - Use of intravitreous bevacizumab to treat macular edema in West Nile virus
      chorioretinitis.

PMID- 22411675
TI  - Peripheral retinal nonperfusion associated with optic nerve hypoplasia and
      lissencephaly.

PMID- 22411677
TI  - Postoperative complications and follow-up after glaucoma surgery.

PMID- 22411676
TI  - Subclinical photoreceptor disruption in response to severe head trauma.

PMID- 22411679
TI  - Radiation exposure during intra-arterial chemotherapy for retinoblastoma.

PMID- 22411681
TI  - Dawbeney Turbervile, MD (1612-1696).
AB  - The year 2012 marks the quatercentenary of the birth of Dawbeney
      Turbervile,MD(1612-1696), one-time Royalist soldier and later ophthalmologist to
      England's Princess Anne, the diarist Samuel Pepys, the natural philosopher Robert
      Boyle, and the astronomer Walter Pope. Turbervile is remarkable for many reasons:
      He specialized at a time when generalization was prized; though he was a
      qualified physician, he also practiced the trade of surgery. Furthermore, he
      provided in his communications with the Royal Society early descriptions of
      achromatopsia, ocular foreign body removal with a magnet, and tic doloreaux. He
      is a forebear worth remembering

PMID- 22411682
TI  - Electroacupuncture frequency-related transcriptional response in rat arcuate
      nucleus revealed region-distinctive changes in response to low- and high
      frequency electroacupuncture.
AB  - Electroacupuncture (EA) has been clinically applied for treating different
      medical conditions, such as pain, strain, and immune diseases. Low- and high
      frequency EAs have distinct therapeutic effects in clinical practice and
      experimental studies. However, the molecular mechanism of this difference remains
      obscure. The arcuate nucleus (Arc) is a critical region of the hypothalamus and
      is responsible for the effect of EA stimulation to remote acupoints. Gene
      expression profiling provides a powerful tool with which to explore the basis of
      physiopathological responses to external stimulus. In this study, using cDNA
      microarray, we investigated gene expressions in the rat Arc region induced by low
      frequency (2-Hz) and high-frequency (100-Hz) EAs to two remote acupoints, zusanli
      (ST36) and sanyinjiao (SP6). We have found that more genes were differentially
      regulated by 2-Hz EA than 100-Hz EA (154 vs. 66 regulated genes/ESTs) in Arc,
      especially those related to neurogenesis, which was confirmed by qRT-PCR. These
      results demonstrate that the expression level of genes in the Arc region could be
      effectively regulated by low-frequency EA, compared with high-frequency EA,
      helping to uncover the mechanisms of the therapeutic effects of the low-frequency
      EA. Our results also indicate different-frequency EAs are spatially specific.

PMID- 22411683
TI  - Dermal clearance model for epidermal bioavailability calculations.
AB  - A computational model for estimating dermal clearance in humans of arbitrary,
      nonmetabolized solutes is presented. The blood capillary component employs slit
      theory with contributions from both small (10 nm) and large (50 nm) slits. The
      lymphatic component is derived from previously reported clearance measurements of
      dermal and subcutaneous injections of (131)I-albumin in humans. Model parameters
      were fitted to both blood capillary permeability data and lymphatic clearance
      data. Small molecules are cleared largely by the blood and large molecules by the
      lymph. The combined model shows a crossover behavior at approximately 29 kDa, in
      acceptable agreement with the reported value of 16 kDa. When combined with
      existing models for stratum corneum permeability and appropriate measures of
      tissue binding, the developed model has the potential to significantly improve
      tissue concentration estimates for large or highly protein-bound permeants
      following dermal exposure.

PMID- 22411684
TI  - Further study is needed to assess ototoxicity from organophosphates and paraquat.

PMID- 22411686
TI  - Polygalacturonase-inhibitor proteins in pearl millet: possible involvement in
      resistance against downy mildew.
AB  - Polygalacturonase-inhibitor protein (PGIP) is a defense protein found in plant
      cell walls. It prevents the degradation of pectin by modulating the endo
      polygalacturonase activity. The present study has used heterologous anti-bean
      PGIP probes to investigate the role of PGIP in pearl millet [Pennisetum glaucum
      (L) R. Br.] resistance against downy mildew caused by oomycete pathogen
      Sclerospora graminicola (Sacc.) Schroet. Northern blot analysis using bean pgip2
      DNA fragment as probe showed an early and marked induction of transcripts (~1.2
      kb) upon pathogen-inoculation in pearl millet cultivar resistant to downy mildew,
      with the maximum level observed at 24 and 48 h post-inoculation (h.p.i.). Western
      blot analysis of pearl millet total cell wall proteins using antibodies against
      bean PGIP showed the presence of a major band of ~43 kDa, and several minor ones.
      The protein accumulation was higher in resistant seedlings than in susceptible
      seedlings with a differential expression observed only in the case of
      incompatible interaction. Immunocytochemical localization in epidermal peelings
      of coleoptiles and tissue-printing showed a similar trend in the PGIP
      accumulation. PGIP was found to localize in the epidermal as well as in the
      vascular regions of tissues. Higher accumulation was observed in the stomatal
      guard cells of resistant cultivar inoculated with the pathogen. PGIP activity of
      pearl millet total protein extracts when assayed against Aspergillus niger PG
      displayed differential PG inhibitory activities between the resistant and
      suceptible cultivars with resistant sample showing the highest inhibition of 16%,
      post-pathogen treatment. Thus, PGIP appeared to be an important player in pearl
      millet-S. graminicola interaction leading to host resistance.

PMID- 22411687
TI  - A chronic case of adult-onset Sandifer syndrome.

PMID- 22411688
TI  - Spatial patterns of the tau pathology in progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is characterized neuropathologically by
      neuronal loss, gliosis, and the presence of tau-immunoreactive neuronal and glial
      cell inclusions affecting subcortical and some cortical regions. The objectives
      of this study were to determine (1) the spatial patterns of the tau
      immunoreactive pathology, viz., neurofibrillary tangles (NFT), oligodendroglial
      inclusions (GI), tufted astrocytes (TA), and Alzheimer's disease-type neuritic
      plaques (NP) in PSP and (2) to investigate the spatial correlations between the
      histological features. Post-mortem material of cortical and subcortical regions
      of eight PSP cases was studied. Spatial pattern analysis was applied to the NFT,
      GI, TA, NP, abnormally enlarged neurons (EN), surviving neurons, and glial cells.
      NFT, GI, and TA were distributed either at random or in regularly distributed
      clusters. The EN and NP were mainly randomly distributed. Clustering of NFT and
      EN was more frequent in the cortex and subcortical regions, respectively.
      Variations in NFT density were not spatially correlated with the densities of
      either GI or TA, but were positively correlated with the densities of EN and
      surviving neurons in some regions. (1) NFT were the most widespread tau
      immunoreactive pathology in PSP being distributed randomly in subcortical regions
      and in regular clusters in cortical regions, (2) GI and TA were more localized
      and exhibited a regular pattern of clustering in subcortical regions, and (3)
      neuronal and glial cell pathologies were not spatially correlated.

PMID- 22411689
TI  - Oral supplementation with dihomo-gamma-linolenic acid (DGLA)-enriched oil
      increases serum DGLA content in healthy adults.
AB  - Dihomo-gamma-linolenic acid (DGLA) is one of the polyunsaturated fatty acids, and
      is expected to show anti-allergic activity. We examined the effects of
      supplementation with DGLA-enriched oil (450 mg as free DGLA) for 4 weeks in
      healthy adults in a randomized controlled study. The DGLA composition in the
      total fatty acids of serum phospholipids increased from 2.0 to 3.4%, and returned
      to the initial level after a 4-week washout. No side effects or changes in blood
      biochemical parameters were observed. These results indicate that serum DGLA
      content can be safely increased by supplementation with 450 mg DGLA under these
      conditions.

PMID- 22411690
TI  - Pneumococcal capsular serotypes and lung infection.

PMID- 22411691
TI  - Neural-differentiated mesenchymal stem cells incorporated into muscle stuffed
      vein scaffold forms a stable living nerve conduit.
AB  - Autologous nerve grafts to bridge nerve gaps have donor site morbidity and
      possible neuroma formation resulting in development of various methods of
      bridging nerve gaps without using autologous nerve grafts. We have fabricated an
      acellular muscle stuffed vein seeded with differentiated mesenchymal stem cells
      (MSCs) as a substitute for nerve autografts. Human vein and muscle were both
      decellularized by liquid nitrogen immersion with subsequent hydrolysis in
      hydrochloric acid. Human MSCs were subjected to a series of treatments with a
      reducing agent, retinoic acid, and a combination of trophic factors. The
      differentiated MSCs were seeded on the surface of acellular muscle tissue and
      then stuffed into the vein. Our study showed that 35-75% of the cells expressed
      neural markers such as S100b, glial fibrillary acidic protein (GFAP), p75 NGF
      receptor, and Nestin after differentiation. Histological and ultra structural
      analyses of muscle stuffed veins showed attachment of cells onto the surface of
      the acellular muscle and penetration of the cells into the hydrolyzed fraction of
      muscle fibers. We implanted these muscle stuffed veins into athymic mice and at 8
      weeks post-implantation, the acellular muscle tissue had fully degraded and
      replaced with new matrix produced by the seeded cells. The vein was still intact
      and no inflammatory reactions were observed proving the biocompatibility and
      biodegradability of the conduit. In conclusion, we have successfully formed a
      stable living nerve conduit which may serve as a substitute for autologous
      nerves.

PMID- 22411692
TI  - Left ventricular discoordination index measured by speckle tracking strain rate
      imaging predicts reverse remodelling and survival after cardiac resynchronization
      therapy.
AB  - AIMS: This study aimed to evaluate the predictive value of a baseline speckle
      tracking strain rate imaging-derived discoordination index for response to
      cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Ninety-seven
      patients with QRS >=120 ms and left ventricular (LV) ejection fraction <=35% were
      prospectively followed after CRT in the Mayo CRT Registry. The LV discoordination
      index (stretch/shortening or thinning/thickening during ejection) was calculated
      from three types of deformation, radial, circumferential, and longitudinal, using
      two-dimensional speckle tracking strain rate imaging. The benefit of CRT was
      evaluated by reverse remodelling (i.e. reduction of LV end-systolic volume >=15%
      at 6-month follow-up) and survival. The optimal cut-off value of the baseline
      discoordination index in discriminating responders from non-responders was
      determined by receiver operating characteristic curve analysis. Significant
      differences in baseline indices between responders and non-responders were noted
      for radial and circumferential discoordination indices. A mid-ventricular radial
      discoordination index (RDI-M) >38% best predicted responders, especially in
      patients with ischaemic cardiomyopathy (area under the curve 0.86 for all
      patients, sensitivity 80%, and specificity 91%). Death occurred in 28 patients
      over a median follow-up of 3.2 years. When adjusted for confounding variables,
      lack of significant discoordination (RDI-M <38%) before CRT was associated with a
      particularly high mortality (hazard ratio 7.05, 95% confidence interval 2.45
      26.0). CONCLUSION: LV discoordination assessed by speckle tracking RDI-M imaging
      was able to predict reverse remodelling at 6 months and survival of patients who
      received CRT.

PMID- 22411693
TI  - Cytoskeletal protein expression and its association within the hydrophobic
      membrane of artificial cell models.

PMID- 22411694
TI  - Relationship between prolactin levels and subjective endocrine-related adverse
      effects in patients with schizophrenia receiving long-term treatment with
      amisulpride.
AB  - INTRODUCTION: We have investigated the categorical prevalence of
      hyperprolactinemia and examined the relationship between prolactin levels and
      subjective endocrine-related adverse effects in schizophrenia patients treated
      with amisulpride during a 1-year period. METHODS: A total of 111 patients with
      schizophrenia who were either started on or switched to amisulpride were assessed
      for prolactin levels and endocrine-related adverse effects using 6 items derived
      from the Liverpool University neuroleptic side-effect rating scale (LUNSERS) at
      baseline, 8 weeks, and 1 year. RESULTS: 10 were antipsychotic-naive, 23 were
      antipsychotic free for 1 month, 54 discontinued their medication during 1 month
      prior to study, and 24 maintained their antipsychotics at baseline. At 1 year,
      hyperprolactinemia was found in 75.9% of men and 85.7% of women. Significant
      increases in mean prolactin levels at week 8 in both sexes were found; this was
      followed by a significant decrease over 1 year only in women. The proportions of
      both sexes with hyperprolactinemia increased from baseline to week 8 but remained
      unchanged at 1 year. Scores on the endocrine-related items of the LUNSERS
      improved significantly from baseline to week 8 in both sexes and then remained
      consistent during maintenance treatment. Prolactin levels were significantly
      higher in the group with baseline hyperprolactinemia than in the group without
      baseline hyperprolactinemia at all assessment points. CONCLUSIONS: Amisulpride
      commonly induces hyperprolactinemia. Although the percentage of patients with
      hyperprolactinemia remained unchanged during maintenance treatment, serum
      prolactin levels significantly decreased among women. Self-reported endocrine
      related side effects were not associated with prolactin elevation during
      amisulpride treatment.

PMID- 22411695
TI  - Evolution of germline-limited sequences in two populations of the ciliate
      Chilodonella uncinata.
AB  - Ciliates are microbial eukaryotes that separate their nuclear functions into a
      germline micronucleus and a somatic macronucleus. During development of the
      macronucleus the genome undergoes a series of reorganization events that includes
      the precise excision of intervening DNA. Here, we determine the architecture of
      four loci in the micronuclear and macronuclear genomes of the ciliate
      Chilodonella uncinata and compare the levels of variation in micronuclear-limited
      sequences to macronuclear destined sequences at two of these loci. We find that
      within a population, germline-limited sequences are evolving at the same rate as
      other putatively neutral sites, but between populations germline-limited
      sequences are accumulating mutations at a much faster rate than other sites. We
      also find evidence of macronuclear recombination and incomplete elimination of
      intervening DNA, which result in increased diversity in the macronuclear genome.
      Our results support the assertion that the unusual genomic features of ciliates
      can result in rapid and unpredicted patterns of diversification.

PMID- 22411696
TI  - Observation of methanol behavior in fuel cells in situ by NMR spectroscopy.
AB  - The chemical conversion of methanol in direct methanol fuel cells was followed in
      situ by NMR spectroscopy. Comparing data of the methanol oxidation on Pt and PtRu
      anode catalysts allowed the role of Ru in both Faradaic and non-Faradaic
      reactions to be investigated. The spatial distributions of chemicals could also
      be determined. (Picture: T1-T4=inlet and outlet tubes.).

PMID- 22411697
TI  - Mimicking the action of folding chaperones by Hamiltonian replica-exchange
      molecular dynamics simulations: application in the refinement of de novo models.
AB  - The efficiency of using a variant of Hamiltonian replica-exchange molecular
      dynamics (Chaperone H-replica-exchange molecular dynamics [CH-REMD]) for the
      refinement of protein structural models generated de novo is investigated. In CH
      REMD, the interaction between the protein and its environment, specifically, the
      electrostatic interaction between the protein and the solvating water, is varied
      leading to cycles of partial unfolding and refolding mimicking some aspects of
      folding chaperones. In 10 of the 15 cases examined, the CH-REMD approach sampled
      structures in which the root-mean-square deviation (RMSD) of secondary structure
      elements (SSE-RMSD) with respect to the experimental structure was more than 1.0
      A lower than the initial de novo model. In 14 of the 15 cases, the improvement
      was more than 0.5 A. The ability of three different statistical potentials to
      identify near-native conformations was also examined. Little correlation between
      the SSE-RMSD of the sampled structures with respect to the experimental structure
      and any of the scoring functions tested was found. The most effective scoring
      function tested was the DFIRE potential. Using the DFIRE potential, the SSE-RMSD
      of the best scoring structures was on average 0.3 A lower than the initial model.
      Overall the work demonstrates that targeted enhanced-sampling techniques such as
      CH-REMD can lead to the systematic refinement of protein structural models
      generated de novo but that improved potentials for the identification of near
      native structures are still needed.

PMID- 22411699
TI  - Ophthalmic manifestations of paranasal sinus disease: a clinical grading system.
AB  - BACKGROUND: Ophthalmic complications are common manifestations of paranasal sinus
      disease. We propose a clinical grading system to standardize the category,
      treatment, and outcome of these complications. METHODS: Forty-two patients with
      paranasal sinus disease-induced ophthalmic complications were included in the
      study. The patients were categorized according to their clinical presentation:
      Grade I, patients with anatomical disturbance; Grade II, patients with ophthalmic
      functional involvement; Grade III, patients with orbital infection; and Grade IV,
      patients with visual impairment. RESULTS: The age of the patients ranged from 8
      to 65 years (mean = 30 years). Overall, 36% patients had ophthalmologic
      manifestations with anatomical disturbance (Grade I), 26% had functional
      disturbance (Grade II), 26% had orbital infections (Grade III), and 12% had
      visual loss (Grade IV). The cause of the ophthalmic manifestations was allergic
      fungal sinusitis in 50%, chronic rhinosinusitis in 36%, acute sinusitis in 10%,
      and mucocele in 4%. The most common ophthalmic manifestation was proptosis (36%),
      followed by orbital infection (26%), functional involvement (26%), and visual
      impairment (12%). The patients underwent functional endoscopic sinus surgery and
      medical treatment when indicated. The outcome in Grades I, II, and III was
      favorable; the outcome in Grade IV was not favorable. CONCLUSION: This simple
      clinical grading system provides a useful tool for assessing the overall status
      of ophthalmic complications of Acute and chronic paranasal sinus disease at the
      initial clinical assessment and for subsequent management of these complications.

PMID- 22411700
TI  - Role of ErbB2 mediated AKT and MAPK pathway in gall bladder cell proliferation
      induced by argemone oil and butter yellow. Argemone oil and butter yellow induced
      gall bladder cell proliferation.
AB  - The effect of noncytotoxic doses of argemone oil (AO) and butter yellow (BY), the
      common adulterants in edible oil, on free radical generation and signaling
      pathway for cell proliferation in primary cells of gall bladder (GB) was
      undertaken. AO and BY showed no cytotoxicity at 0.1 MUl/ml and 0.1 MUg/ml
      concentration, respectively. AO caused significant increase in ROS after 30 min
      and RNS after 24 h in GB cells while no change was observed following BY
      treatment. Enhanced level of COX-2 was observed following AO (0.1 MUl/ml) and BY
      (0.1 MUg/ml) treatment to cells for 24 h. AO treatment caused phosphorylation of
      ErbB2, AKT, ERK, and JNK along with increased thymidine uptake indicating cell
      proliferation ability in GB cells. BY treatment also showed significant
      expression of these proteins with the exception of phosphorylated JNK. These
      results suggest that AO and BY have cell proliferative potential in GB cells
      following up-regulation of COX-2 and ErbB2; however, their downstream signaling
      molecules and free radical generation have differential response, indicating that
      the mechanism of proliferation is different for both compounds and may have
      relevance in gall bladder cancer.

PMID- 22411698
TI  - Biodegradable biomatrices and bridging the injured spinal cord: the corticospinal
      tract as a proof of principle.
AB  - Important advances in the development of smart biodegradable implants for axonal
      regeneration after spinal cord injury have recently been reported. These advances
      are evaluated in this review with special emphasis on the regeneration of the
      corticospinal tract. The corticospinal tract is often considered the ultimate
      challenge in demonstrating whether a repair strategy has been successful in the
      regeneration of the injured mammalian spinal cord. The extensive know-how of
      factors and cells involved in the development of the corticospinal tract, and the
      advances made in material science and tissue engineering technology, have
      provided the foundations for the optimization of the biomatrices needed for
      repair. Based on the findings summarized in this review, the future development
      of smart biodegradable bridges for CST regrowth and regeneration in the injured
      spinal cord is discussed.

PMID- 22411701
TI  - Antioxidant activity and low toxicity of (E)-1-(1-(methylthio)-1-(selenopheny)
      hept-1-en-2-yl) pyrrolidin-2-one.
AB  - The aim of the present study was to evaluate the potential pharmacological and
      toxicological properties of (E)-1-(1-(methylthio)-1-(selenopheny) hept-1-en-2-yl)
      pyrrolidin-2-one (compound 1), an organoselenium compound. In vitro experiments
      showed that compound 1 presented a reduction in the lipid peroxidation induced by
      Fe2+ in thiobarbituric acid-reactive species (TBARS) production, and in the
      generation of reactive species caused by Fe2+/malonate in DCFH-DA oxidation. The
      high dose (500 mg/kg) induced an increase on ALT but not on AST activity.
      Hepatic, but not cerebral, delta-ALA-D activity from mice treated with 500 mg/kg
      presented a significant inhibition. Brain catalase activity was significantly
      inhibited by 100 mg/kg whereas hepatic catalase activity showed a significant
      increase at all doses. Hepatic lipid peroxidation was diminished only at lowest
      dose (100 mg/kg) whereas for brain tissue, all doses induced a significant
      reduction in TBARS levels. Brain and liver ascorbic acid contents were increased
      only at highest dose of compound 1. Urea and creatinine levels were not
      significantly altered by treatments. This is a promising compound with
      antioxidant activity and low toxicity, suggesting the potential beneficial
      activity of compound 1 against oxidative damage in many parameters studied in
      rats and mice.

PMID- 22411702
TI  - In vivo imaging and biodistribution of multimodal polymeric nanoparticles
      delivered to the optic nerve.
AB  - The use of nanoparticles for targeted delivery of therapeutic agents to sites of
      injury or disease in the central nervous system (CNS) holds great promise.
      However, the biodistribution of nanoparticles following in vivo administration is
      often unknown, and concerns have been raised regarding potential toxicity. Using
      poly(glycidyl methacrylate) (PGMA) nanoparticles coated with polyethylenimine
      (PEI) and containing superparamagnetic iron oxide nanoparticles as a magnetic
      resonance imaging (MRI) contrast agent and rhodamine B as a fluorophore, whole
      animal MRI and fluorescence analyses are used to demonstrate that these
      nanoparticles (NP) remain close to the site of injection into a partial injury of
      the optic nerve, a CNS white matter tract. In addition, some of these NP enter
      axons and are transported to parent neuronal somata. NP also remain in the eye
      following intravitreal injection, a non-injury model. Considerable infiltration
      of activated microglia/macrophages occurs in both models. Using magnetic
      concentration and fluorescence visualization of tissue homogenates, no
      dissemination of the NP into peripheral tissues is observed. Histopathological
      analysis reveals no toxicity in organs other than at the injection sites.
      Multifunctional nanoparticles may be a useful mechanism to deliver therapeutic
      agents to the injury site and somata of injured CNS neurons and thus may be of
      therapeutic value following brain or spinal cord trauma.

PMID- 22411704
TI  - Rhotekin modulates differentiation of cultured neural stem cells to neurons.
AB  - Rhotekin is a downstream signal of Rho and is expressed in the central nervous
      system. However, the physiological role of rhotekin in the development of neural
      stem cells (NSCs) into neurons is unknown. In this study, we knocked down the
      expression of rhotekin protein with small interfering RNA (siRNA) in the NSCs and
      in neural differentiated cells and measured cell proliferation, differentiation,
      neurite length, and survival. By using immunocytochemistry and Western blot, the
      production of rhotekin was observed in NSCs and neuronal cells. Furthermore,
      rhotekin production was increased in accordance with neural differentiation.
      Rhotekin knock-down reduced 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) activity and increased the cell death 72 hr after transfection in
      neurons. On the other hand, in NSCs, rhotekin knock-down increased MTT activity
      and the number of 5-bromo-2'-deoxyuridine (BrdU)-positive cells. In the present
      study, we demonstrated that rhotekin is required for maintenance and survival of
      neurons and positively regulates differentiation and neurite outgrowth. Moreover,
      we found that rhotekin is produced in NSCs and that the role of rhotekin is to
      regulate cell proliferation negatively. In conclusion, these results suggest that
      rhotekin is one of the key molecules in the differentiation of NSCs into neurons.

PMID- 22411703
TI  - Scientific workflow management in proteomics.
AB  - Data processing in proteomics can be a challenging endeavor, requiring extensive
      knowledge of many different software packages, all with different algorithms,
      data format requirements, and user interfaces. In this article we describe the
      integration of a number of existing programs and tools in Taverna Workbench, a
      scientific workflow manager currently being developed in the bioinformatics
      community. We demonstrate how a workflow manager provides a single, visually
      clear and intuitive interface to complex data analysis tasks in proteomics, from
      raw mass spectrometry data to protein identifications and beyond.

PMID- 22411705
TI  - Community Study of maternal mortality in South West Nigeria: how applicable is
      the sisterhood method.
AB  - A significant reduction in maternal mortality was witnessed globally in the year
      2010, yet, no significant reduction in the maternal mortality ratio (MMR) in
      Nigeria was recorded. The absence of accurate data on the numbers, causes and
      local factors influencing adverse maternal outcomes has been identified as a
      major obstacle hindering appropriate distribution of resources targeted towards
      improving maternal healthcare. This paper reports the first community based study
      that measures the incidence of maternal mortality in Ibadan, Nigeria using the
      indirect sisterhood method and explores the applicability of this method in a
      community where maternal mortality is not a rare event. A community-based study
      was conducted in Ibadan using the principles of the sisterhood method developed
      by Graham et al. for developing countries. Using a multi-stage sampling design
      with stratification and clustering, 3,028 households were selected. All persons
      approached agreed to take part in the study (a participation rate of 100%), with
      2,877 respondents eligible for analysis. There was a high incidence of maternal
      mortality in the study setting: 1,324/6,519 (20.3%) sisters of the respondents
      had died, with 1,139 deaths reportedly related to pregnancy, childbirth or the
      puerperium. The MMR was 7,778 per 100,000 live births (95% CI 7,326-8,229).
      Adjusted for a published Total Fertility Rate of 6.0, the MMR was 6,525 per
      100,000 live births (95% CI 6,144-6,909). Women in Ibadan were dying more from
      pregnancy related complications than from other causes. Findings of this study
      have implications for midwifery education, training and practice and for the
      first time provide policy makers and planners with information on maternal
      mortality in the community of Ibadan city and shed light on the causes of
      maternal mortality in the area.

PMID- 22411706
TI  - Peri-implantation lethality in mice lacking the PGC-1-related coactivator
      protein.
AB  - BACKGROUND: Members of the PPARgamma coactivator-1 (PGC-1) family are central
      transcriptional coactivators that regulate cell metabolic processes ranging from
      mitochondrial biogenesis to oxidative respiration. PGC-1-related coactivator
      (PPRC1 or PRC), initially identified as a member of the PGC-1 family, is believed
      to regulate mitochondria biogenesis, respiration pathways, and cell
      proliferation. However, its physiological role is not clearly understood. Here,
      we investigate the biological functions of PPRC1 in vivo using PPRC1 deficient
      mice generated by gene targeting. RESULTS: Homozygous deficient PPRC1 mice failed
      to form egg cylinders and died after implantation but before embryonic day 6.5,
      whereas mice heterozygous for PPRC1 were viable, fertile and indistinguishable
      from their wild-type littermates. Furthermore, PPRC1 mRNA was expressed at the
      embryonic stage before implantation and was rapidly up-regulated during the first
      day of embryoid body formation. The PPRC1 mRNA was then subsequently down
      regulated, although its precise function at this stage of development was
      unclear. CONCLUSIONS: This is the first study to suggest a nonredundant role for
      PPRC1 in mouse early embryonic development.

PMID- 22411707
TI  - Solid-state nuclear magnetic resonance study of the physical stability of
      electrospun drug and polymer solid solutions.
AB  - A major challenge in utilizing the amorphous form of an active pharmaceutical
      ingredient (API) in a final oral dosage form is preventing crystallization over
      time and ensuring stability. One method to improve stability is lowering the
      mobility of an API by formulating as a solid solution with an excipient. In this
      work, we use electrospinning to prepare solid solutions of API, aliskiren (SPP)
      or indomethacin (IND), and a polymer, polyvinylpyrrolidone (PVP). The stability
      of the solid solutions over 6-month storage in a desiccator at 40  degrees C was
      investigated. Using X-ray diffraction and differential scanning calorimetry, it
      was determined that no crystals were present in the four formulations tested--1:1
      SPP-PVP, 4:1 SPP-PVP, 1:1 IND-PVP, and 2:1 IND-PVP at any time. Solid-state
      nuclear magnetic resonance relaxation time measurements were used to determine
      whether phase separation of the API and polymer occurred during the study period.
      It was found that all formulations remained homogeneous down to at least a 2-10
      nm length scale, indicating that for these APIs, electrospinning is an acceptable
      method for forming stable amorphous solid solutions.

PMID- 22411708
TI  - A case of rotational atherectomy after implantation of the Medtronic CoreValve
      bioprosthesis.

PMID- 22411709
TI  - Significant increase of oxidase activity through the genetic incorporation of a
      tyrosine-histidine cross-link in a myoglobin model of heme-copper oxidase.

PMID- 22411710
TI  - Temperature dependence of surface nanobubbles.
AB  - The temperature dependence of nanobubbles was investigated experimentally using
      atomic force microscopy. By scanning the same area of the surface at temperatures
      from 51  degrees C to 25  degrees C it was possible to track geometrical changes
      of individual nanobubbles as the temperature was decreased. Interestingly,
      nanobubbles of the same size react differently to this temperature change; some
      grow whilst others shrink. This effect cannot be attributed to Ostwald ripening,
      since the growth and shrinkage of nanobubbles appears to occur in distinct
      patches on the substrate. The total nanobubble volume per unit area shows a
      maximum around 33  degrees C, which is comparable with literature where
      experiments were carried out with increasing temperature. This underlines the
      stability of surface nanobubbles.

PMID- 22411711
TI  - Visualizing next-generation sequencing data with JBrowse.
AB  - JBrowse is a web-based genome browser, allowing many sources of data to be
      visualized, interpreted and navigated in a coherent visual framework. JBrowse
      uses efficient data structures, pre-generation of image tiles and client-side
      rendering to provide a fast, interactive browsing experience. Many of JBrowse's
      design features make it well suited for visualizing high-volume data, such as
      aligned next-generation sequencing reads.

PMID- 22411712
TI  - Clinical anatomy related to the hepatic veins for right lobe living donor liver
      transplantation.
AB  - The complexity of liver reconstruction has limited partial right lobe living
      donor liver transplantation. It is largely due to the difficulty of dealing with
      the middle hepatic vein. We sought to define the anatomic features of hepatic
      veins. Forty-one fresh adult livers, 43 formalin-fixed adult cadaver livers, and
      91 adult liver corrosion casts were used for the study. We determined the number
      of branches, the maximum diameter, the whole length, the extrahepatic length of
      the hepatic veins, and the deviation of the middle hepatic vein from the main
      portal fissure. Nakamura and Tsuzuki's classification of hepatic vein types was
      used. Type A, B, and C accounted for 59.4, 27.8, and 12.8% of all specimens in
      this study, respectively. The middle and left hepatic veins formed a common trunk
      in 60.3% of the specimens, and the length of the common trunk was 1.12 +/- 0.62
      cm. The degree of deviation to the right of the middle hepatic vein from the main
      portal fissure was 14.11 degrees  +/- 12.65 degrees . The frequency of hepatic
      vein types and the degree of deviation to the right of the middle hepatic vein in
      this study is markedly different from that reported in other literature. The
      anatomic features of the hepatic veins in this study suggest that right lobe
      living donor liver transplantation is more suitable for Chinese.

PMID- 22411713
TI  - Development and evaluation of an English language measure of detection of word
      final plurality markers: the University of Western Ontario Plurals Test.
AB  - PURPOSE: This article describes the development and evaluation of The University
      of Western Ontario (UWO) Plurals Test, which is an English language measure of
      detection of the word-final fricative cue for plurality. METHOD: Normative data
      are provided for 26 listeners with normal hearing and 24 listeners with hearing
      impairment (children and adults), as are evaluations of the acoustical properties
      of the stimuli, the test's test-retest reliability, and the test's sensitivity to
      changes in hearing aid signal processing (e.g., nonlinear frequency compression).
      RESULTS: Results indicate reliable, repeated outcome measurement at the level of
      the individual. When compared to a global measure of real-world listening
      preference, the UWO Plurals Test was found to be somewhat sensitive to the
      effects of changes in hearing aid signal processing. CONCLUSION: Findings suggest
      potential use of the UWO Plurals Test to evaluate aided and unaided ability of
      listeners between the ages of 6 and 81 years to detect the word-final fricatives
      /s/ and /z/ as they occur in English plural nouns.

PMID- 22411714
TI  - Crisscross pulmonary artery with double aortic arch: an unusual association.
AB  - Anomalies of pulmonary artery origin are rare. Crisscross pulmonary artery origin
      is a rare benign anomaly characterized by the left pulmonary artery arising
      superiorly and to the right side of the right pulmonary artery. The condition is
      usually accompanied by a conotruncal anomaly. Here, we report a child with
      crisscross pulmonary arteries and a complete vascular ring formed by a double
      aortic arch, which was confirmed by computed tomography angiography. The child
      underwent surgical correction for relief of stridor.

PMID- 22411715
TI  - Palliation using a self-expandable stent in a patient with obstructive right
      ventricular outflow tract after total correction of tetralogy of Fallot: self
      expandable stent in tetralogy of Fallot.
AB  - Total correction of tetralogy of Fallot (TOF) is typically performed within the
      first year of life. However, subsequently, right-ventricular dysfunction often
      progresses by pulmonary stenosis or regurgitation. Although most patients with
      corrected TOF require additional surgery for right-ventricular outflow tract,
      intervention could be an alternative to palliative surgery and associated
      morbidities, especially in children. We describe a palliative application of the
      self-expandable stent in a patient with pulmonary stenosis after total correction
      of TOF who lacked a conduit between the right ventricle and pulmonary artery.

PMID- 22411716
TI  - Reduction in postoperative high-density lipoprotein cholesterol levels in
      children undergoing the Fontan operation.
AB  - Despite the emerging relevance of high-density lipoprotein (HDL) in the
      inflammatory cascade and vascular barrier integrity, HDL levels in children
      undergoing cardiac surgery are unexplored. As a measure of HDL levels, the HDL
      cholesterol (HDL-C) in single-ventricle patients was quantified before and after
      the Fontan operation, and it was determined whether relationships existed between
      the duration and the type of postoperative pleural effusions. The study
      prospectively enrolled 12 children undergoing the Fontan operation. Plasma HDL-C
      levels were measured before and after cardiopulmonary bypass. The outcome
      variables of interest were the duration and type of chest tube drainage (chylous
      vs. nonchylous). The Kendall rank correlation coefficient and the Wilcoxon rank
      sum test were used. There were 11 complete observations. The median preoperative
      HDL-C level for all the subjects was 30 mg/dl (range, 24-53 mg/dl), and the
      median postcardiopulmonary bypass level was 21 mg/dl (range, 14-46 mg/dl) (p =
      0.004). There was a tendency toward a moderate inverse correlation (-0.42)
      between the postcardiopulmonary bypass HDL-C level and the duration of chest tube
      drainage, but the result was not statistically significant (p = 0.07). In the
      chylous effusion group, the median postcardiopulmonary bypass HDL-C tended to be
      lower (16 vs. 23 mg/dl; p = 0.09). After the Fontan operation, the plasma HDL-C
      levels in children are significantly reduced. It is reasonable to conclude that
      the reduction in HDL-C reflects reduced plasma levels of HDL particles, which may
      have pertinent implications in postoperative pleural effusions given the
      antiinflammatory and endothelial barrier functions of HDL.

PMID- 22411717
TI  - Heart rate variability abnormalities in young patients with dilated
      cardiomyopathy.
AB  - Heart rate variability (HRV) has become the conventionally accepted term for
      describing variations in both instantaneous heart rate and R-R intervals. In the
      pediatric age group, HRV has been investigated in healthy children, diabetics,
      respiratory distress syndrome of the newborn, and sudden infant death syndrome.
      This study aimed to evaluate HRV in pediatric patients with dilated
      cardiomyopathy and to compare it with that of age-matched normal subjects. The
      study evaluated 21 patients with dilated cardiomyopathy: 11 females (mean age, 7
      +/- 4 years; range, 2-17 years) and 10 males (mean age, 10 +/- 6 years; range, 2
      18 years). Dilated cardiomyopathy (DCM) was diagnosed according to commonly
      accepted criteria after a noninvasive cardiologic examination, echocardiography,
      and 24-h Holter monitoring (MR45 and MR45-3 Oxford recorder). The patients were
      divided into six groups according to age, sex, and type of cardiomyopathy. Heart
      rate variability was recorded and analyzed in the time domain. The patients with
      DCM showed an abnormal HRV pattern. Particularly in the 5-6-year-old male patient
      group, the HRV values all were significantly increased (p = 0.05). In the 2-6
      year-old female patient group, the mean cycle length, the standard deviation of
      all normal sinus R-R intervals during 24 h (SDNN), and the standard deviation of
      the average normal sinus R-R intervals for all 5-min segments (SDANN) were
      significantly increased (p = 0.05). The 13-18-year-old female patient group
      showed a significant reduction in SDNN and the mean of the standard deviation of
      all normal sinus R-R intervals for all 5-min segments (SDNNi) (p = 0.05). The
      modification of the HRV pattern in the time domain, partially age- and gender
      dependent modification, may reflect an imbalance of the autonomic nervous system
      in children who show a delayed or reduced activity, such as pediatric patients
      with DCM.

PMID- 22411718
TI  - Recapitulating long-QT syndrome using induced pluripotent stem cell technology.
AB  - The generation of patient-specific stem cells by reprogramming somatic cells to
      induced pluripotent stem cells (iPSC) provides the basis for a promising new type
      of in vitro disease models. Patient-specific iPSC derived from individuals with
      hereditary disorders can be differentiated into somatic cells in vitro, thus
      allowing the pathophysiology of the diseases to be studied on a cellular level.
      Different types of long-QT syndrome have been successfully modeled using this
      approach, demonstrating that the iPSC-derived patient-specific cardiomyocytes
      recapitulated key features of the disease in vitro. This approach will likely
      serve to model other monogenetic or polygenetic cardiovascular disorders in the
      future. Moreover, test platforms based on patient-specific iPSC could be used to
      test the potential of drug candidates to induce QT-interval prolongation or other
      unwanted side effects, screen for novel cardiovascular drugs, or to tailor
      medical therapy to the specific needs of a single patient.

PMID- 22411720
TI  - Cycloartane triterpenoids from Cassia occidentalis.
AB  - A phytochemical investigation of the whole plants of Cassia occidentalis led to
      the isolation of two new cycloartane triterpenoids, cycloccidentalic acids A and
      B (1 and 2), and five new related saponins, cycloccidentalisides I-V (3-7),
      together with sixteen known compounds. The structures of the isolated compounds
      were elucidated through detailed spectroscopic analyses, including 1D and 2D NMR
      techniques, and chemical methods. Compounds 2 and 5 showed modest anti-HIV-1
      activities with EC50 values of 2.23 uM and 4.36 uM, respectively, in comparison
      to the positive control.

PMID- 22411721
TI  - Paeoniflorin inhibits proliferation of fibroblast-like synoviocytes through
      suppressing G-protein-coupled receptor kinase 2.
AB  - Paeoniflorin (Pae) is a monoterpene glucoside and the main component of the total
      glucosides of paeony (TGP) extracted from the roots of Paeonia lactiflora. Its
      anti-inflammatory effect is associated with regulating G-protein-coupled
      receptors (GPCRs) signaling. The aim of this study was to explore the expression
      change of G-protein-coupled receptor kinase 2 (GRK2) in fibroblast-like
      synoviocytes (FLS) and the effect of Pae. Pae was obtained and purified from the
      roots of Paeonia lactiflora. We investigated the expression of GRK2 in synovium
      during the inflammatory process and assessed the effects of a specific GRK2
      inhibitor and Pae on proliferation, cAMP level, and protein kinase A (PKA)
      activity of FLS in vitro. Additionally, the effect of Pae on GRK2 expression in
      FLS was detected in vitro. Expression of GRK2 in synovium from CIA rats increased
      during the inflammatory process. The specific GRK2 inhibitor suppressed
      proliferation and increased the cAMP level as well as PKA activity of FLS, and
      Pae had the same effects. Furthermore, Pae decreased GRK2 expression in FLS in
      vitro. Our results indicate that a chronic inflammatory process in CIA induces
      upregulation of GRK2 expression in FLS, and Pae can reverse this change, which
      might be one of the important mechanisms for Pae regulating GPCRs signaling and
      suppressing the proliferation of FLS in CIA.

PMID- 22411722
TI  - Pharmacokinetics of valerenic acid in rats after intravenous and oral
      administrations.
AB  - Valerenic acid (VA), a sesquiterpenoid, is one of the major secondary bioactive
      metabolites of  VALERIANA OFFICINALIS L. Until now  IN VIVO studies on the
      absorption, bioavailability, disposition, and metabolism of VA are limited. We
      established and validated an LC-MS/MS assay for the determination of VA in rat
      plasma and successfully used this method for pharmacokinetic studies in rats
      after intravenous (i. v.) and oral administrations. The plasma concentration-time
      data was analyzed by both non-compartmental and compartmental approaches using
      WinNonlin software. Following i. v. administration, the disposition of VA in rat
      plasma was biphasic, subdivided into a fast distribution and a slow elimination
      phase. The half-life of the distribution phase was 6-12 min, and that of the
      terminal elimination phase 6-46 h, indicating a possible large tissue binding.
      Disposition PK of valerenic acid after oral treatment was also described by a two
      compartment model with a clearance (CL/F) of 2-5 L . h (-1) . kg (-1) and volume
      of distribution of (V (d)) 17-20 L . kg (-1). The extent of absorption (F) after
      oral administration was estimated to be 33.70 % with a half-life of 2.7-5 h. Dose
      proportionality was observed in terms of dose and AUCs, suggesting linear
      pharmacokinetics at the dose levels studied in rats.

PMID- 22411723
TI  - Antinociceptive and antispasmodic effects of the essential oil of Ocimum
      micranthum: potential anti-inflammatory properties.
AB  - The antinociceptive and antispasmodic properties of the essential oil of OCIMUM
      micranthum (EOOM) were characterized. In mice, EOOM (15-100 mg . kg (-1), p. o.)
      reduced both the writhing responses induced by acetic acid and the licking-time
      induced by formalin, being inert on the hot plate test. In rat trachea, EOOM
      relaxed sustained contractions induced by KCl or carbachol (CCh). Its
      constituents, ( E)- [( E)-MC] and ( Z)-methyl cinnamate [( Z)-MC], reproduced
      several effects of EOOM. Inhaled as aerosol, EOOM prevented tracheal
      hyperresponsiveness to KCl or CCh in ovalbumin-sensitized animals after antigen
      challenge. Thus, EOOM exerts peripheral analgesia in nociception of inflammatory
      origin and has antispasmodic actions on rat airways under an inflammatory
      environment. Its effects are mainly due to ( E)-MC, which makes this substance
      potentially interesting for studies involving conjunctly smooth muscle cells,
      nociception, and inflammation. Other EOOM constituents also appear to be involved
      in its pharmacological actions.

PMID- 22411724
TI  - Heat exposure of Cannabis sativa extracts affects the pharmacokinetic and
      metabolic profile in healthy male subjects.
AB  - The most important psychoactive constituent of  CANNABIS SATIVA L. is Delta (9)
      tetrahydrocannabinol (THC). Cannabidiol (CBD), another important constituent, is
      able to modulate the distinct unwanted psychotropic effect of THC. In natural
      plant extracts of  C. SATIVA, large amounts of THC and CBD appear in the form of
      THCA-A (THC-acid-A) and CBDA (cannabidiolic acid), which can be transformed to
      THC and CBD by heating. Previous reports of medicinal use of cannabis or cannabis
      preparations with higher CBD/THC ratios and use in its natural, unheated form
      have demonstrated that pharmacological effects were often accompanied with a
      lower rate of adverse effects. Therefore, in the present study, the
      pharmacokinetics and metabolic profiles of two different  C. SATIVA extracts
      (heated and unheated) with a CBD/THC ratio > 1 were compared to synthetic THC
      (dronabinol) in a double-blind, randomized, single center, three-period cross
      over study involving 9 healthy male volunteers. The pharmacokinetics of the
      cannabinoids was highly variable. The metabolic pattern was significantly
      different after administration of the different forms: the heated extract showed
      a lower median THC plasma AUC (24 h) than the unheated extract of 2.84 vs. 6.59
      pmol h/mL, respectively. The later was slightly higher than that of dronabinol
      (4.58 pmol h/mL). On the other hand, the median sum of the metabolites (THC, 11
      OH-THC, THC-COOH, CBN) plasma AUC (24 h) was higher for the heated than for the
      unheated extract. The median CBD plasma AUC (24 h) was almost 2-fold higher for
      the unheated than for the heated extract. These results indicate that use of
      unheated extracts may lead to a beneficial change in metabolic pattern and
      possibly better tolerability.

PMID- 22411725
TI  - Biflavonoids of Dacrydium balansae with potent inhibitory activity on dengue 2
      NS5 polymerase.
AB  - In order to find new molecules for antiviral drug design, we screened 102 ethyl
      acetate extracts from New-Caledonian flora for antiviral activity against the
      dengue 2 virus RNA-dependant RNA polymerase (DV-NS5 RdRp). The leaf extract of
      Dacrydium balansae, which strongly inhibited the DV-NS5, was submitted to
      bioguided fractionation. Four biflavonoids ( 1- 4), three sterols ( 5- 7), and
      two stilbene derivatives ( 8- 9) were identified and evaluated for their
      antiviral potential on the DV-NS5 RdRp. Biflavonoids appeared to be potent
      inhibitors of DV-NS5 RdRp with IC (50)s between 0.26 and 3.12 uM. Inhibitory
      activity evaluations against the RNA polymerase from other Flaviviridae viruses
      allowed us to conclude that these compounds are specific inhibitors of the DV RNA
      polymerase. The strongest inhibitions were observed with hinokiflavone ( 4), but
      podocarpusflavone A ( 2) is the strongest noncytotoxic inhibitor of the DV-NS5
      and it also displayed polymerase inhibitory activity in a DV replicon. A
      preliminary structure-activity relationship study (SARs) revealed the necessity
      of the biflavonoid skeleton, the influence of number and position of
      methoxylations, and the importance of a free rotation of the linkage between the
      two apigenin monomers of the biflavonoids. To the best of our knowledge,
      podocarpusflavone A ( 2) is the strongest noncytotoxic non-nucleotide molecule
      exhibiting a specific inhibitory activity against the RNA polymerase domain of DV
      NS5 and thus is promising for chemotherapy development against dengue fever.

PMID- 22411726
TI  - Intestinal transport of pure diester-type alkaloids from an aconite extract
      across the Caco-2 cell monolayer model.
AB  - Aconitine (AC), mesaconitine (MA), and hypaconitine (HA) are the active alkaloids
      identified in aconite tuber, an important traditional Chinese medicine. The study
      is aimed to investigate their intestinal transport profiles and potential
      interaction during the intestinal absorption using the Caco-2 cell monolayer
      model. All three alkaloids had good permeability with  P(app) values greater than
      1 * 10 (-6) cm . s (-1). However, AC, MA, and HA in a mixture and as an extract,
      in both cases with the same content of alkaloids, showed higher transport
      efficiency in the apical to basolateral, and lower transport efficiency in the
      basolateral to apical directions. Digoxin, as a P-glycoprotein (P-gp) substrate,
      was substantially effluxed in the basolateral to apical direction but inhibited
      by the three alkaloids. Furthermore, the backwards transport of MA and HA was
      inhibited by the P-gp inhibitor verapamil. These observations indicated that the
      three alkaloids may not only be P-gp inhibitors but also its substrates; they
      interact with each other and can potentially enhance their own bioavailability
      when taken concomitantly.

PMID- 22411727
TI  - Effect of silymarin and harpagoside on inflammation reaction of BEAS-2B cells, on
      ciliary beat frequency (CBF) of trachea explants and on mucociliary clearance
      (MCC).
AB  - Silymarin and harpagoside are derived from drugs which are used for their
      protective effects against hepatotoxicity and inflammatory processes. Both are
      now investigated with respect to the respiratory tract. They were able to reduce
      the release of the inflammatory cytokine RANTES (regulated on activation, normal
      T cells expressed and secreted) from BEAS-2B cells in a concentration-dependent
      manner when stimulated by a cytokine mix (10 ng/mL of TNF- alpha and IFN- gamma).
      This effect was not due to a possible toxic effect (control experiments using LDH
      release as a marker). Silymarin but not harpagoside was able to increase ciliary
      beat frequency. Effects were comparable to positive controls (isoprenaline and
      salbutamol). Silymarin also increases mucociliary clearance. In conclusion,
      silymarin should be further investigated for its clinical use in distinct
      respiratory diseases.

PMID- 22411728
TI  - Intestinal permeability of forskolin by in situ single pass perfusion in rats.
AB  - The intestinal permeability of forskolin was investigated using a single pass
      intestinal perfusion (SPIP) technique in rats. SPIP was performed in different
      intestinal segments (duodenum, jejunum, ileum, and colon) with three
      concentrations of forskolin (11.90, 29.75, and 59.90 ug/mL). The investigations
      of adsorption and stability were performed to ensure that the disappearance of
      forskolin from the perfusate was due to intestinal absorption. The results of the
      SPIP study indicated that forskolin could be absorbed in all segments of the
      intestine. The effective permeability (P (eff)) of forskolin was in the range of
      drugs with high intestinal permeability. The P (eff) was highest in the duodenum
      as compared to other intestinal segments. The decreases of P (eff) in the
      duodenum and ileum at the highest forskolin concentration suggested a saturable
      transport process. The addition of verapamil, a P-glycoprotein inhibitor,
      significantly enhanced the permeability of forskolin across the rat jejunum. The
      absorbed fraction of dissolved forskolin after oral administration in humans was
      estimated to be 100 % calculated from rat P (eff). In conclusion, dissolved
      forskolin can be absorbed readily in the intestine. The low aqueous solubility of
      forskolin might be a crucial factor for its poor oral bioavailability.

PMID- 22411729
TI  - Carboline alkaloids from Psammosilene tunicoides and their cytotoxic activities.
AB  - Five new carboline alkaloids, tunicoidines A-E ( 1- 5), and two known carboline
      alkaloids, 1-acetyl-beta-carboline-3-carboxylic acid ( 6) and 1-acetyl-3
      carbomethoxyl- beta-carboline ( 7), were isolated for the first time from the
      root of Psammosilene tunicoides. The structures of the new carboline alkaloids
      were established on the basis of 1D- and 2D-NMR, and HR-MS spectroscopic
      analyses. The seven compounds were evaluated for cytotoxicity against A549,
      HCT116, ZR-75-30, and HL-60 cell lines. However, only compound 7 had potent
      cytotoxic activity against the HCT116 cell line with an IC (50) value of 9.67
      ug/mL, while the others showed no cytotoxic activities against the four tested
      cell lines.

PMID- 22411730
TI  - Point-of-purchase tobacco access and advertisement in food stores.

PMID- 22411731
TI  - Pulmonary vein isolation during cryoballoon ablation using the novel Achieve
      inner lumen mapping catheter: a feasibility study.
AB  - AIMS: Cryoballoon (CB) ablation has proven very effective in achieving pulmonary
      vein isolation (PVI). The Achieve catheter (AC) is a novel inner lumen catheter
      designed to be used in conjunction with the CB, which serves the double purpose
      of a guidewire and a mapping catheter. We aimed to evaluate the feasibility of CB
      ablation in conjunction with the novel AC, in terms of PVI and safety in a series
      of patients affected by drug resistant paroxysmal atrial fibrillation (AF).
      METHODS AND RESULTS: Seventy patients (49 male) affected by paroxysmal AF were
      assigned to CB PVI using the AC as a mapping catheter. Patients underwent loop
      Holter monitoring 1, 3 and 6 months after ablation. Isolation occurred in 98% of
      PVs with the CB-AC association without having switching to a regular guidewire.
      Pulmonary vein isolation could be documented by real-time (RT) recordings in 47%
      (132) of veins. Time to isolation was significantly longer in PVs exhibiting
      early left atrium-PV reconnection if compared with veins with sustained isolation
      (117 +/- 25 s vs. 59 +/- 25 s; P< 0,005). No serious complications occurred; four
      transient phrenic nerve palsies occurred all resolving completely before the end
      of the procedure. CONCLUSION: Cryoballoon ablation in conjunction with the novel
      AC is feasible, safe, and most importantly affords PVI in nearly all veins
      without having to switch to a regular guidewire. However, RT recordings could be
      documented in only 47% of pulmonary veins.

PMID- 22411732
TI  - Glu121-Lys319 salt bridge between catalytic and N-terminal domains is pivotal for
      the activity and stability of Escherichia coli aminopeptidase N.
AB  - Escherichia coli aminopeptidase N (ePepN) belongs to the gluzincin family of M1
      class metalloproteases that share a common primary structure with consensus zinc
      binding motif (HEXXH-(X18)-E) and an exopeptidase motif (GXMEN) in the active
      site. There is one amino acid, E121 in Domain I that blocks the extended active
      site grove of the thermolysin like catalytic domain (Domain II) limiting the
      substrate to S1 pocket. E121 forms a part of the S1 pocket, while making critical
      contact with the amino-terminus of the substrate. In addition, the carboxylate of
      E121 forms a salt bridge with K319 in Domain II. Both these residues are
      absolutely conserved in ePepN homologs. Analogous Glu-Asn pair in tricon
      interacting factor F3 (F3) and Gln-Asn pair in human leukotriene A(4) hydrolase
      (LTA(4) H) are also conserved in respective homologs. Mutation of either of these
      residues individually or together substantially reduced or entirely eliminated
      enzymatic activity. In addition, thermal denaturation studies suggest that the
      mutation at K319 destabilizes the protein as much as by 3.7  degrees C, while
      E121 mutants were insensitive. Crystal structure of E121Q mutant reveals that the
      enzyme is inactive due to the reduced S1 subsite volume. Together, data presented
      here suggests that ePepN, F3, and LTA(4) H homologs adopted a divergent evolution
      that includes E121-K319 or its analogous pairs, and these cannot be interchanged.

PMID- 22411733
TI  - Tap water or "sterile" water for sinus irrigations: what are our patients using?
AB  - BACKGROUND: Nasal saline irrigations are a valuable, widely used adjunct for the
      management of chronic rhinosinusitis. Due to potential concerns regarding
      infection, patients are commonly recommended to use distilled, bottled, or boiled
      tap water when mixing these solutions. Anecdotally, patients frequently inform
      otolaryngologists that they use tap water for irrigation preparation. The purpose
      of this study was to assess patient adherence to preparation guidelines. METHODS:
      This study was a cross-sectional, anonymous survey of 100 consecutive patients
      using nasal saline irrigations for chronic rhinosinusitis on the instruction of
      the senior author. Patients received their instructions in a standardized manner
      including printed handouts and had been instructed to use distilled, bottled, or
      boiled tap water. RESULTS: Patients almost uniformly reported improvement in
      their symptoms with the use of saline irrigations. No single water preparation
      was used by a majority of patients. However, tap water was used by 48% and the
      most common reason cited for using tap water was convenience. Of the patients
      using bottled, distilled, or boiled tap water, 65% described the process as
      "mildly" or "moderately" inconvenient. A large majority (70%) of patients report
      not adhering to cleaning instructions for their sinus rinse bottles. CONCLUSION:
      Despite standardized instructions for the preparation of saline irrigation
      solutions, many patients use untreated tap water. The extremely rare, but
      typically fatal, risk of meningoencephalitis from Naegleria fowlerii makes this a
      potential health hazard.

PMID- 22411734
TI  - Folic acid deficiency inhibits neural rosette formation and neuronal
      differentiation from rhesus monkey embryonic stem cells.
AB  - Evidence from epidemiological studies has proved that periconceptional use of
      folic acid (FA) can significantly reduce the risk of neural tube defects (NTDs).
      However, it is hard to explore when and how FA plays roles in neurogenesis and
      brain development in vivo, especially in human or other nonhuman primate systems.
      Primate embryonic stem cell (ESC) lines are ideal models for studying cell
      differentiation and organogenesis in vitro. In the present study, the roles of FA
      in neural differentiation were assessed in a rhesus monkey ESC system in vitro.
      The results showed no significant difference in the expression of neural
      precursor markers, such as nestin, Sox-1, or Pax-6, among neural progenitors
      obtained from different FA concentrations or with the FA antagonist methotrexate
      (MTX). However, FA depletion decreased cell proliferation and affected embryoid
      body (EB) and neural rosette formation, as well as neuronal but not neuroglia
      differentiation. Our data imply that the ESC system is a suitable model for
      further exploring the mechanism of how FA works in prevention of NTDs in
      primates.

PMID- 22411735
TI  - Multifunctionalized CMCht/PAMAM dendrimer nanoparticles modulate the cellular
      uptake by astrocytes and oligodendrocytes in primary cultures of glial cells.
AB  - The efficiency of the treatments involving CNS disorders is commonly diminished
      by the toxicity, reduced stability and lack of targeting of the administered
      neuroactive compounds. In this study, we have successfully multifunctionalized
      CMCht/PAMAM dendrimer nanoparticles by coupling the CD11b antibody and loading MP
      into the nanoparticles. The modification of the new antibody-conjugated
      nanoparticles was confirmed by S-TEM observation and (1) H NMR and FTIR
      spectroscopy. Cytotoxicity assays revealed that the conjugates did not affect the
      viability of both primary cultures of glial and microglial cells. Trace analyses
      of FITC-labelled nanoparticles revealed that the uptake of antibody-conjugated
      nanoparticles was conserved in microglial cells but significantly decreased in
      astrocytes and oligodendrocytes. Thus, this study demonstrates that antibody
      conjugation contributes to a modulation of the internalization of these
      nanocarriers by different cell types, which might be of relevance for specific
      targeting of CNS cell populations.

PMID- 22411736
TI  - Normalized shape and location of perturbed craniofacial structures in the Xenopus
      tadpole reveal an innate ability to achieve correct morphology.
AB  - BACKGROUND: Embryonic development can often adjust its morphogenetic processes to
      counteract external perturbation. The existence of self-monitoring responses
      during pattern formation is of considerable importance to the biomedicine of
      birth defects, but has not been quantitatively addressed. To understand the
      computational capabilities of biological tissues in a molecularly tractable model
      system, we induced craniofacial defects in Xenopus embryos, then tracked tadpoles
      with craniofacial deformities and used geometric morphometric techniques to
      characterize changes in the shape and position of the craniofacial structures.
      RESULTS: Canonical variate analysis revealed that the shapes and relative
      positions of perturbed jaws and branchial arches were corrected during the first
      few months of tadpole development. Analysis of the relative movements of the
      anterior-most structures indicates that misplaced structures move along the
      anterior-posterior and left-right axes in ways that are significantly different
      from their normal movements. CONCLUSIONS: Our data suggest a model in which
      craniofacial structures use a measuring mechanism to assess and adjust their
      location relative to other local organs. Understanding the correction mechanisms
      at work in this system could lead to the better understanding of the adaptive
      decision-making capabilities of living tissues and suggest new approaches to
      correct birth defects in humans.

PMID- 22411737
TI  - Accelerated aging as evidenced by increased telomere shortening and mitochondrial
      DNA depletion in patients with type 2 diabetes.
AB  - Although shortened telomeres were shown associated with several risk factors of
      diabetes, there is lack of data on their relationship with mitochondrial
      dysfunction. Therefore, we compared the relationship between telomere length and
      mitochondrial DNA (mtDNA) content in patients with type 2 diabetes mellitus
      (T2DM; n = 145) and in subjects with normal glucose tolerance (NGT; n = 145).
      Subjects were randomly recruited from the Chennai Urban Rural Epidemiology Study.
      mtDNA content and telomere length were assessed by Real-Time PCR.
      Malonodialdehyde, a marker of lipid peroxidation was measured by thiobarbituric
      acid reactive substances (TBARS) using fluorescence methodology. Adiponectin
      levels were measured by radioimmunoassay. Oxidative stress as determined by lipid
      peroxidation (TBARS) was significantly (p < 0.001) higher in patients with T2DM
      compared to NGT subjects. In contrast, the mean telomere length, adiponectin and
      mtDNA content were significantly (p < 0.001) lower in patients with T2DM compared
      to NGT subjects. Telomere length was positively correlated with adiponectin, HDL,
      mtDNA content and good glycemic/lipid control and negatively correlated with
      adiposity and insulin resistance. On regression analysis, shortened telomeres
      showed significant association with T2DM even after adjusting for waist
      circumference, insulin resistance, triglyceride, HDL, adiponectin, mtDNA & TBARS.
      mtDNA depletion showed significant association with T2DM after adjusting for
      waist circumference and adiponectin but lost its significance when further
      adjusted for telomere length, TBARS and insulin resistance. Our study emphasizes
      the clustering of accelerated aging features viz., shortened telomeres, decreased
      mtDNA content, hypoadiponectinemia, low HDL, and increased oxidative stress in
      Asian Indian type 2 diabetes patients.

PMID- 22411738
TI  - Chemopreventive effects of NSAIDs as inhibitors of cyclooxygenase-2 and inducers
      of apoptosis in experimental lung carcinogenesis.
AB  - Roles of cyclooxygenase (COX) enzyme and intrinsic pathway of apoptosis have been
      explored for the chemopreventive effects of non-steroidal anti-inflammatory drugs
      (NSAIDs) on 9,10-dimethyl benz(a)anthracene (DMBA)-induced lung cancer in rat
      model. 16 weeks after the administration of DMBA, morphological analysis revealed
      the occurrences of tumours and lesions, which were regressed considerably with
      the co-administration of indomethacin and etoricoxib, the two NSAIDs under
      investigation. DMBA group was marked by hyperplasia and dysplasia as observed by
      histological examination, and these features were corrected to a large extent by
      the two NSAIDs. Elevated levels of COX-2 were seen in the DMBA group, the enzyme
      responsible for prostaglandin synthesis during inflammation and cancer, whilst
      the expression of the constitutive isoform, COX-1, was equally expressed in all
      the groups. Apoptosis was quantified by studying the activities of apaf-1,
      caspase-9, and 3 by immunofluorescence and western blots. Their activities were
      found to diminish in the DMBA-treated animals as compared to the other groups.
      Fluorescent co-staining of the isolated broncho-alveolar lavage cells showed
      reduced number of apoptotic cells in the DMBA group, indicating decrease in
      apoptosis after carcinogen administration. The present results thus suggest that
      the mechanism of cancer chemoprevention of NSAIDs may include the suppression of
      COX-2 and the induction of apoptosis.

PMID- 22411739
TI  - Reconstruction of divergence-free velocity fields from cine 3D phase-contrast
      flow measurements.
AB  - Three-dimensional phase-contrast velocity vector field mapping shows great
      potential for clinical applications; however measurement inaccuracies may limit
      the utility and robustness of the technique. While parts of the error in the
      measured velocity fields can be minimized by background phase estimation in
      static tissue and magnetic field monitoring, considerable inaccuracies remain.
      The present work introduces divergence-reduction processing of 3D phase-contrast
      flow data based on a synergistic combination of normalized convolution and
      divergence-free radial basis functions. It is demonstrated that this approach
      effectively addresses erroneous flow for image reconstructions from both fully
      sampled and undersampled data. Using computer simulations and in vivo data
      acquired in the aorta of healthy subjects and a stenotic valve patient it is
      shown that divergence arising from measurement imperfections can be reduced by up
      to 87% resulting in improved vector field representations. Based on the results
      obtained it is concluded that integration of the divergence-free condition into
      postprocessing of vector fields presents an efficient approach to addressing flow
      field inaccuracies.

PMID- 22411740
TI  - Regarding the vascular anatomy of muscles with a special focus on the gracilis
      muscle.

PMID- 22411741
TI  - The effect of neutral ion aggregate formation on the electrical conductivity of
      an ionic liquid and its mixtures with chloroform.
AB  - We have studied the electrical conductivity of mixtures of the ionic liquid (IL)
      [C(2)mim][NTf(2)] with chloroform for various concentrations at a temperature of
      303 K by both experiments and MD simulations. The molar conductivities exhibit an
      initial increase with decreasing IL concentration, which again sharply decreases
      in the region of highly diluted IL concentrations. This behavior is according to
      a competition between 1) the decreasing viscosity with increasing chloroform
      concentration due to fluidizing the mixture, and 2) the decreasing amount of
      charge carriers due to the formation of neutral IL aggregates. The simulated
      molar conductivities and their concentration dependence are found to be in
      reasonable agreement with the experimentally determined values, suggesting that
      essential correlations between the solvated ionic species in the solution are
      well represented. Both experiments and simulations show that the Nernst-Einstein
      relation drastically overestimates the conductivity of the solutions at low IL
      concentrations. According to our MD simulation data, this observation is due to
      the extensive formation of neutral aggregates in the low-concentration regime.

PMID- 22411742
TI  - Transdermal delivery using a novel electrochemical device, part 2: in vivo study
      in humans.
AB  - A single-center, open-label, and dose-escalation clinical trial has been
      performed using a novel electrochemical transdermal patch comprising a drug
      loaded hydrogel sandwiched between two silver electrodes. The lower electrode is
      attached flatly to skin via an adhesive layer. This noniontophoretic device
      produces flux enhancement via voltage-induced electrolysis of the water in the
      hydrogel. A voltage application of 2 V over 60 s produced release of
      approximately 315 to 340 MUg of fentanyl from a patch. A single-voltage
      application at t = 16 h produced a maximum plasma level of approximately 200
      pg/mL before patch removal at t = 41 h. Consecutive voltage applications at t =
      16 h and t = 40 h produced a maximum plasma level of approximately 730 pg/mL. The
      lag time between voltage application and achievement of a plasma profile plateau
      is longer than that reported for an iontophoretic patch. The patch's advantage is
      production of an on-demand plasma profile without the use of potentially
      irritating iontophoresis. In contrast to a passive transdermal system, it is
      possible to adjust the plasma profile by using voltage application. It is not
      necessary to apply a continual current, in contrast to iontophoretic systems.

PMID- 22411743
TI  - A definitive NMR solution for a simple and accurate measurement of the magnitude
      and the sign of small heteronuclear coupling constants on protonated and non
      protonated carbon atoms.
AB  - Simply successful: a proton-selective HSQMBC-TOCSY experiment can be used to
      measure small proton-carbon ((n)J(CH); n>1) coupling constants on both protonated
      and non-protonated carbon atoms. The method combines in a single pulse scheme all
      the benefits of the widely used HSQMBC and HSQC-TOCSY experiments. The magnitude
      and the sign of (n)J(CH) can be determined simply with excellent accuracy.

PMID- 22411744
TI  - Expression of axonal protein degradation machinery in sympathetic neurons is
      regulated by nerve growth factor.
AB  - Deficiencies in protein degradation and proteolytic function within neurons are
      linked to a number of neurodegenerative diseases and developmental disorders.
      Compartmentalized cultures of peripheral neurons were used to investigate the
      properties and relative abundance of the proteolytic machinery in the axons and
      cell bodies of sympathetic and sensory neurons. Immunoblotting of axonal proteins
      demonstrated that LAMP2, LC3, and PSMA2 were abundant in axons, suggesting that
      lysosomes, autophagosomes and proteasomes were located in axons. Interestingly,
      the expression of proteins associated with lysosomes and proteasomes were
      upregulated selectively in axons by NGF stimulation of the distal axons of
      sympathetic neurons, suggesting that axonal growth and maintenance requires local
      protein turnover. The regulation of the abundance of both proteasomes and
      lysosomes in axons by NGF provides a link between protein degradation and the
      trophic status of peripheral neurons. Inhibition of proteasomes located in axons
      resulted in an accumulation of ubiquitinated proteins in these axons. In
      contrast, lysosome inhibition in axons did not result in an accumulation of
      ubiquitinated proteins or the transferrin receptor, a transmembrane protein
      degraded by lysosomes. Interestingly, lysosomes were transported both
      retrogradely and anterogradely, so it is likely that ubiquitinated proteins that
      are normally destined for degradation by lysosomes in axons can be transported to
      the cell bodies for degradation. In summary, proteasomal degradation occurs
      locally, whereas proteins degraded by lysosomes can most likely either be
      degraded locally in axons or be transported to cell bodies for degradation.

PMID- 22411745
TI  - Functionalization of poly(ferrocenyldimethylsilane) via lithiation of the
      cyclopentadienyl rings.
AB  - The metallation of the cyclopentadienyl (Cp) ligands of
      poly(ferrocenyldimethylsilane) (PFDMS) can be performed by reaction with the
      Schlosser's base pair t-BuLi/KOt-Bu in THF. Subsequent treatment with a series of
      electrophiles affords a range of Cp-substituted polymers with up to an average of
      1.8 new substituents per repeating unit. NMR studies on polymers containing
      trimethylsilyl groups and deuterium on the Cp rings are indicative of high
      regioselectivity with selective metallation at the beta-carbon.

PMID- 22411746
TI  - Dose quantification of topical drug delivery to the paranasal sinuses by
      fluorescein luminosity calculation.
AB  - BACKGROUND: Our group has previously described a novel method of objectively
      quantifying the temporospatial distribution of sinonasal irrigation in a
      nonanesthetized patient. The purpose of this study is to refine this technique to
      provide an accurate method of determining concentration of dose delivery as well.
      METHODS: An endoscope at a fixed position within 2 dissected cadaveric heads was
      used to image 4 subsites under blue light. Each site was dosed with 3 mL of
      successively increasing concentrations of fluorescein-labeled saline. In vitro
      images of the labeled saline were also captured over a range of depths. Images
      were exported into a graphics editing program that was used to calculate
      luminosity at 3 regions per subsite. The relationship between luminosity and
      fluorescein concentration was calculated using a Pearson product-moment
      correlation coefficient. Significance was determined using a 2-tailed Student t
      test. RESULTS: Luminosity of the irrigation delivered to the maxillary sinus,
      lamina papyracea, ethmoid roof, and frontal sinus positively correlated with
      fluorescein concentration over a range of 0.1 to 0.01 mg/mL (n = 6; r = 0.95, p <
      0.001; r = 0.94, p < 0.001; r = 0.92, p < 0.001; and r = 0.94, p < 0.001;
      respectively). There was no significant difference between luminosities of a 0.01
      mg/mL irrigation layer subtending a range of depths up to 6.6 mm. CONCLUSION: The
      described method is capable of determining the concentration of fluorescein
      delivery to a mucosal surface via objective luminosity quantification. Our data
      suggest that this method will remain accurate regardless of the potential for
      heterogeneous pooling of irrigation. This method may be used to optimize delivery
      strategies of a variety of topical sinonasal therapies.

PMID- 22411747
TI  - Titmuss revisited: from tax credits to markets.
AB  - Petersen and Lippert-Rasmussen argue that persons who decide to be organ donors
      should receive a tax break, and then defend their view against eight possible
      objections. However, they misunderstand the Titmuss-style concerns that might be
      raised against their proposal. This does not mean that it should be rejected,
      but, instead, that when it is reconfigured to meet the Titmuss-style charges
      against it, they should support legalizing markets in human organs rather than
      merely offering tax breaks to encourage their donation.

PMID- 22411748
TI  - A proposed non-consequentialist policy for the ethical distribution of scarce
      vaccination in the face of an influenza pandemic.
AB  - The current UK policy for the distribution of scarce vaccination in an influenza
      pandemic is ethically dubious. It is based on the planned outcome of the maximum
      health benefit in terms of the saving of lives and the reduction of illness. To
      that end, the population is classified in terms of particular priority groups. An
      alternative policy with a non-consequentialist rationale is proposed in the
      present work. The state should give the vaccination, in the first instance, to
      those who are at risk of catching the pandemic flu in the line of their duties of
      public employment. Thereafter, if there is not sufficient vaccine to give all
      citizens equally an effective dose, the state should give all citizens an equal
      chance of receiving an effective dose. This would be the just thing to do because
      the state has a duty to treat each and all of its citizens impartially and they
      have a corresponding right to such impartial treatment. Although this article
      specifically refers to the UK, it is considered that the suggested alternative
      policy would be applicable generally. The duty to act justly is not merely a
      local one.

PMID- 22411749
TI  - A general method to determine sampling windows for nonlinear mixed effects models
      with an application to population pharmacokinetic studies.
AB  - Optimal design methods have been proposed to determine the best sampling times
      when sparse blood sampling is required in clinical pharmacokinetic studies.
      However, the optimal blood sampling time points may not be feasible in clinical
      practice. Sampling windows, a time interval for blood sample collection, have
      been proposed to provide flexibility in blood sampling times while preserving
      efficient parameter estimation. Because of the complexity of the population
      pharmacokinetic models, which are generally nonlinear mixed effects models, there
      is no analytical solution available to determine sampling windows. We propose a
      method for determination of sampling windows based on MCMC sampling techniques.
      The proposed method attains a stationary distribution rapidly and provides time
      sensitive windows around the optimal design points. The proposed method is
      applicable to determine sampling windows for any nonlinear mixed effects model
      although our work focuses on an application to population pharmacokinetic models.

PMID- 22411750
TI  - Arterial switch operation for double outlet right ventricle (S, D, L) with
      subpulmonary ventricular septal defect.
AB  - We describe a rare case of double outlet right ventricle (DORV; S, D, L) with
      subpulmonary ventricular septal defect (VSD) treated successfully with arterial
      switch operation (ASO) and VSD baffle. Compared with our limited experience in
      three cases of DORV (S, D, L) with subpulmonary VSD corrected by modified
      Rastelli procedure, ASO is a preferable choice.

PMID- 22411752
TI  - Influence of radiofrequency energy on polypropylene sutures in atrial tissue.
AB  - OBJECTIVE: Bipolar radiofrequency (RF) ablation is an established technique for
      the surgical treatment of atrial fibrillation. To create complete lesion sets,
      the bipolar device has to be partially inserted into the heart via a purse-string
      suture, which is subject to heat damage. We investigated the influence of RF
      ablation on the structure and function of polypropylene sutures. METHODS: Six
      polypropylene sutures (4/0 Prolene; Ethicon, Norderstedt, Germany) were sutured
      ex vivo into atrial auricles from excised pig hearts. The tissue was treated by
      bipolar, saline-irrigated RF ablation (Cardioblate; Medtronic, Duesseldorf,
      Germany), until increase of tissue impedance pointed out a transmural lesion.
      After fixation in formaldehyde, the sutures were carefully removed and examined
      for ultrastructural damage using scanning electron microscopy, comparing them to
      sutures with intentional damage by instrumental grips. Tensile strength was
      tested applying a force velocity of 200 mm/min. Here, parts from the ablated
      zones were compared with parts from nonablated zones of the same suture. RESULTS:
      We could not find ultrastructural damage in form of heat-induced changes in the
      helical polypropylene structure. Accordingly, the tensile strength of the ablated
      sutures (16.5 to 17.5 N) showed no difference to an untreated suture. In
      contrast, sutures damaged by instruments showed remarkable structural damage and
      could be torn without force. CONCLUSION: Bipolar, saline-irrigated RF ablation
      does not damage polypropylene sutures in spite of the heat applied to the tissue.
      Therefore, it is safe to create bipolar epi/endocardial lesions of the heart
      through polypropylene purse-string sutures.

PMID- 22411751
TI  - Midterm evaluation of biological prosthetic valves in the pulmonary position of
      grown-up patients.
AB  - OBJECTIVES: To examine the midterm clinical outcome of pulmonary valve
      replacement (PVR) with prosthetic valves. METHODS: We reviewed 37 consecutive
      patients who underwent PVR with biological prosthetic valves between September
      1999 and June 2010. The median age was 22.6 years (range: 6 to 70 years; three
      children). The primary diagnosis was Tetralogy of Fallot in 20 patients (54%).
      Valve pathology was regurgitation in 27 patients (72.9%). Cardiac surgery had
      been previously performed in 35 patients (94.5%). The median size of the
      prosthesis was 25 mm (range: 21 to 31 mm). The median follow-up was 42 months
      (range: 1.2 to 129 months). RESULTS: There were no early valve-related deaths.
      Hospital mortality was 2.7% (n = 1) and no patient required early rereplacement
      of prosthesis. Two patients required permanent pacemaker insertion. During follow
      up, there was no late death, reoperation for structural valve degeneration, or
      valve thrombosis. Only one patient required repeated operation for endocarditis
      at 37 months follow-up. The actuarial survival at 5 years was 95.1 +/- 3.8%.
      Overall freedom from reoperation after PVR at 5 years was 93.0 +/- 8.6%. At last
      follow-up, 34 patients (91.8%) were NYHA class I versus 20 patients (54%)
      preoperatively (p < 0.05). In the 35 surviving patients who did not undergo redo
      PVR, there was no-mild regurgitation and the peak PV gradient was 20.4 +/- 10.2
      mm Hg (16.2 +/- 9.3 mm Hg preoperatively). Thirty-two patients (91.4%) had good
      right ventricular function compared with 26 patients (74.2%) preoperatively.
      CONCLUSIONS: PVR with biological prosthetic valves can be performed with good
      midterm survival, functional status, and haemodynamics.

PMID- 22411753
TI  - Clinical outcomes and prognostic factors for surgically resected second primary
      lung cancer.
AB  - BACKGROUND: This study was designed to analyze the predictive factors for
      survival in second primary lung cancer patients following operation. METHODS: A
      total of 1852 patients who underwent resection for primary lung cancer between
      January 1990 and December 2008 were reviewed, retrospectively. RESULTS: Nineteen
      patients were treated for synchronous second primary lung cancer and 23 patients
      were treated for metachronous cancer. The overall 5-year survival rate for
      patients with synchronous second primary lung cancer was comparable to that of
      patients with single-lung cancer (51.4 vs. 48.7%, p = 0.755). The overall 5-year
      survival rate after the first tumor resection in patients with metachronous
      second primary lung cancer was significantly better than that of patients with
      single-lung cancer (85.4 vs. 48.7%, p = 0.003), but was not significantly
      different after the second tumor resection (77.0 vs. 48.7%, p = 0.057).
      CONCLUSION: Surgically resected second primary lung cancer had a survival
      comparable with single-lung cancer. Histologic concordance between the first and
      second tumors, and the pathological stage were important prognostic factors in
      second primary lung cancer.

PMID- 22411754
TI  - Hybrid repair of aortic arch aneurysms in same session.
AB  - BACKGROUND:  Management of thoracic aorta aneurysms-especially the ones including
      aortic arch-is highly complicated. Isolated or nonisolated aortic arch aneurysms
      can be repaired by hybrid procedure especially in patients with comorbidities as
      well as by conventional open methods. METHODS:  Eleven patients who underwent
      total arch debranching and endovascular stent implantation on antegrade route in
      the same session between November 2006 and October 2009 were retrospectively
      evaluated using clinical and perioperative criteria. RESULTS:  The mean age was
      65 +/- 6.2 and nine of the patients were male. Primary technical success rate was
      100%. Mortality, stroke, or transient paraplegia/paraparesia was not seen during
      in-hospital follow-up. Average follow-up period was 36 +/- 13 months and no late
      term aortic pathology was seen. In only one of the patients, endovascular
      reintervention was required for type 1B endoleak. No mortality or neurological
      pathology was seen in long-term postoperative follow-up. CONCLUSION:  Hybrid
      procedures could be performed safely with lower complication and higher success
      rates in the same session via antegrade route and zone 0 graft deployment for
      high-risk cases with isolated or nonisolated aortic arch aneurysms.

PMID- 22411755
TI  - Complete mediastinal lymph node dissection in video-assisted thoracoscopic
      lobectomy versus lobectomy by thoracotomy.
AB  - BACKGROUND: Although video-assisted thoracic surgery (VATS) lobectomy has been
      used more and more frequently for the treatment of patients with early-stage lung
      cancer, controversies are mainly focused on whether the complete mediastinal
      lymph node dissection (MLND) can be achieved by VATS. This retrospective study
      aimed to compare the validity of MLND between VATS and open thoracotomy. METHODS:
      Patients with lung cancer were matched from a pool of pulmonary lobectomies
      performed by one surgeon. Patients undergoing VATS were matched with those
      undergoing thoracotomy in terms of gender, age, clinical tumor stage, tumor
      location, and surgical procedure. RESULTS: After matching, 31 patients in VATS
      group and 31 patients in open group were eligible for analysis. In the VATS and
      open groups, the mean total number of dissected lymph nodes was 28.2 +/- 8.4 and
      29.8 +/- 11.6 (p = 0.517), respectively. In the VATS and open groups, the number
      of N1 nodes was 9.5 +/- 4.1 and 8.4 +/- 4.7 (p = 0.333), respectively. And the
      number of N2 nodes was also similar between the VATS and open group (18.6 +/- 7.0
      vs 21.4 +/- 10.0, p = 0.211). No significant differences were observed between
      the two groups in the operating time, the blood loss, the length of chest tube
      drainage, the length of hospital stay, and the rate of specific complications.
      CONCLUSION: Our early experience suggests that, with regard to the number of the
      dissected lymph nodes, VATS lobectomy can achieve complete MLND, compared with
      the traditional approach. MLND by VATS is technically feasible and safe for early
      stage lung cancer.

PMID- 22411756
TI  - The effects of clipping on thoracic sympathetic nerve in rabbits: early and late
      histopathological findings.
AB  - BACKGROUND: The clipping of the thoracic sympathetic nerve, which has been a
      technique used for approximately the past 10 years, has rapidly become popular
      because of its "bring-back" claim. However, the information regarding the
      mechanism behind this claim is based on investigator's comments and has not been
      proven by objective research, such as the histopathological examination of the
      clipped nerve and/or ganglion. We aimed to evaluate sympathetic regeneration and
      degeneration after clip removal. METHODS: The rabbits were divided into two
      groups with six rabbits per group. For the first group (group A), the sympathetic
      chain was clipped using two titanium clips, and a right thoracotomy was made at
      the T4 and T5 levels. For the second group (group B), the animals were also
      operated on, which was similar to the rabbits in group A. At the end of a 48-hour
      follow-up period, the clips were removed after a second operation. The rabbits in
      group B were followed for 45 days and sympathetic nerves were also examined
      histopathologically. RESULTS: In group A, hemorrhage, fibrinous material,
      polymorphonuclear leukocyte infiltration, and acute inflammation with fat
      necrosis were observed in and around the sympathetic ganglia and trunk. Loss of
      nuclei and vacuolization in some sympathetic ganglia cells were also observed.
      These findings demonstrated severe degeneration of the sympathetic ganglia and
      trunk. For group B, microscopic examination revealed a loss of sympathetic
      ganglion cells as well as fibrosis within and around the ganglia. No signs of
      regeneration were detected and the progression of nerve degeneration was
      observed. CONCLUSIONS: The clips used in our study were shown to cause the
      degeneration of neural structures within 2 days. At the end of the 45 days
      following the removal of the clips, progressive, degenerative changes radiating
      along the axons of the sympathetic cells were seen.

PMID- 22411757
TI  - Pulmonary artery pseudoaneurysm caused by a rare vascular tumor: epithelioid
      hemangioendothelioma.
AB  - We present a case of a 58-year-old female with a rare vascular tumor of
      intermediate malignancy. The initial manifestation was a pseudoaneurysm caused by
      the rupture of the right pulmonary artery after tumor invasion. The diagnosis of
      epithelioid hemangioendothelioma was confirmed by the morphologic and
      immunocytochemical features after surgery. The patient recovered smoothly and
      there has been no evidence of local recurrence or metastasis during the 2 years
      of follow-up. 

PMID- 22411758
TI  - Superiority of video-assisted to standard mediastinoscopy in non-small-cell lung
      cancer staging.
AB  - BACKGROUND: We compared the efficiency of videomediastinoscopy (VM) and standard
      mediastinoscopy (SM) in detecting mediastinal lymph node (MLN) metastasis in non
      small-cell lung cancer (NSCLC) patients. METHODS: By SM method a surgeon sampled
      bilateral paratracheal and subcarinal lymph node stations and then by VM method,
      another surgeon resampled all lymph node stations once more through the same
      incision in the same operative setting. Results of the pathologic examinations of
      two methods were compared. RESULTS: Twenty-seven consecutive mediastinoscopies
      were included. The numbers of nodal stations biopsied in SM and VM were 97 and
      103, respectively. Lymph node metastasis was found in six patients with SM and
      nine patients with VM. Lymph node dissection by thoracotomy revealed metastases,
      which were not found by mediastinoscopy, in two patients. Our study showed an
      accuracy of 92.3% for VM versus 80.7% for SM and corresponding negative
      predictive values of 88.2% and 75%, respectively (p = 0.002; Fig. 1). CONCLUSION:
      This study showed that VM is superior to SM in detecting MLN metastasis in
      patients with NSCLC.

PMID- 22411759
TI  - Hemolysis compromises nitric oxide-dependent vasodilatory responses in patients
      undergoing major cardiovascular surgery.
AB  - BACKGROUND: The hemolytic products cell-free oxyhemoglobin (FHb) and arginase-1
      reduce nitric oxide (NO) bioavailability by scavenging NO and by degrading the NO
      precursor arginine to ornithine, respectively. In this study we evaluated the
      relevance of hemolysis to NO-dependent blood flow in patients undergoing
      cardiovascular surgery. METHODS: Plasma FHb, arginase-1, and amino acid
      concentrations were measured perioperatively. Forearm blood flow (FBF) responses
      to the intra-arterial administered NO-donor sodium nitroprusside (SNP) and the
      endothelium-dependent vasodilator acetylcholine (ACh) were measured by venous
      occlusion plethysmography. RESULTS: When peak values plasma FHb and arginase-1
      were found, vascular dilatation to SNP, but not ACh, was significantly reduced
      compared with 1 day postoperatively, when FHb had returned to baseline levels (p
      < 0.05). Interestingly, plasma FHb concentration was inversely correlated to FBF
      responses to SNP (r -0.93, p < 0.001). In contrast, the increase in arginase-1
      was not biologically relevant as the ratio of plasma arginine to ornithine
      remained constant. CONCLUSION: We conclude that hemolysis with concomitant
      release of FHb during cardiovascular surgery is associated with impaired NO
      dependent forearm blood flow.

PMID- 22411760
TI  - Noble metal-free oxidative electrocatalysts: polyaniline and Co(II)-polyaniline
      nanostructures hosted in nanoporous silica.
AB  - An efficient nanocomposite electrocatalyst composed of mesoporous silica (SBA-15)
      with polyaniline (PANI) nanostructures within its channel pores (PANI/SBA-15) is
      synthesized and characterized. The resulting PANI/SBA-15 is capable of chelating
      Co(II) ions, presumably via its nitrogen atoms on PANI/diamine groups. Both the
      metal-free (SBA-15/PANI) and the Co(II)-doped SBA-15/PANI nanocomposite materials
      showed high electrocatalytic activity for oxidation of L-ascorbic acid, with very
      low overpotential and high current density. The activity of PANI/SBA-15 toward
      oxidation of L-ascorbic acid is comparable to that obtained from a conventional
      Pt/C electrocatalyst.

PMID- 22411761
TI  - New monodisperse magnetic polymer microspheres biofunctionalized for enzyme
      catalysis and bioaffinity separations.
AB  - Magnetic macroporous PGMA and PHEMA microspheres containing carboxyl groups are
      synthesized by multi-step swelling and polymerization followed by precipitation
      of iron oxide inside the pores. The microspheres are characterized by SEM, IR
      spectroscopy, AAS, and zeta-potential measurements. Their functional groups
      enable bioactive ligands of various sizes and chemical structures to couple
      covalently. The applicability of these monodisperse magnetic microspheres in
      biospecific catalysis and bioaffinity separation is confirmed by coupling with
      the enzyme trypsin and huIgG. Trypsin-modified magnetic PGMA-COOH and PHEMA-COOH
      microspheres are investigated in terms of their enzyme activity, operational and
      storage stability. The presence of IgG molecules on microspheres is confirmed.

PMID- 22411762
TI  - Single-shot echo-planar imaging with Nyquist ghost compensation: interleaved dual
      echo with acceleration (IDEA) echo-planar imaging (EPI).
AB  - Echo planar imaging (EPI) is most commonly used for blood oxygen level-dependent
      fMRI, owing to its sensitivity and acquisition speed. A major problem with EPI is
      Nyquist (N/2) ghosting, most notably at high field. EPI data are acquired under
      an oscillating readout gradient and hence vulnerable to gradient imperfections
      such as eddy current delays and off-resonance effects, as these cause
      inconsistencies between odd and even k-space lines after time reversal. We
      propose a straightforward and pragmatic method herein termed "interleaved dual
      echo with acceleration (IDEA) EPI": two k-spaces (echoes) are acquired under the
      positive and negative readout lobes, respectively, by performing phase encoding
      blips only before alternate readout gradients. From these two k-spaces, two
      almost entirely ghost free images per shot can be constructed, without need for
      phase correction. The doubled echo train length can be compensated by parallel
      imaging and/or partial Fourier acquisition. The two k-spaces can either be
      complex averaged during reconstruction, which results in near-perfect
      cancellation of residual phase errors, or reconstructed into separate images. We
      demonstrate the efficacy of IDEA EPI and show phantom and in vivo images at both
      3 T and 7 T.

PMID- 22411763
TI  - Factors that restrict the cell permeation of cyclic prodrugs of an opioid
      peptide, part 3: Synthesis of analogs designed to have improved stability to
      oxidative metabolism.
AB  - Previously, our laboratory reported that cyclic peptide prodrugs of the opioid
      peptide H-Tyr-D-Ala-Gly-Phe-D-Leu-OH (DADLE) are metabolized by cytochrome P450
      (CYP450) enzymes, which limits their systemic exposure after oral dosing to
      animals. In an attempt to design more metabolically stable cyclic prodrugs of
      DADLE, we synthesized analogs of DADLE cyclized with a coumarinic acid linker
      (CA; CA-DADLE), which contained modifications in the amino acid residues known to
      be susceptible to CYP450 oxidation. Metabolic stability and metabolite
      identification studies of CA-DADLE and its analogs were then compared using rat
      liver microsomes (RLM), guinea pig liver microsomes (GPLM), and human liver
      microsomes (HLM), as well as recombinant human recombinant cytochrome P450 3A4
      (hCYP3A4). Similar to the results observed for CA-DADLE, incubation of its
      analogs with RLM, GPLM, and HLM resulted in monohydroxylation of an amino acid
      side chain on these cyclic prodrugs. When CA-DADLE was incubated with hCYP3A4,
      similar oxidative metabolism of the peptide was observed. In contrast, incubation
      of the CA-DADLE analogs with hCYP3A4 showed that these amino-acid-modified
      analogs are not substrates for this CYP450 isozyme. These results suggest that
      the amino-acid-modified analogs of CA-DADLE prepared in this study could be
      stable to metabolic oxidation by CYP3A4 expressed in human intestinal mucosal
      cells.

PMID- 22411764
TI  - Orientational ordering of ionic liquids near a charged mica surface.
AB  - The self-assembly of ions in room-temperature ionic liquids adsorbed on a mica
      surface is studied using molecular dynamics simulations. Four liquids from the 1
      methyl,n-alkylimidazolium bis(trifluoromethylsulfonyl)imide ([C(n)mim][NTf(2)])
      family are investigated, where n ranges between 2 and 8. Cations with ethyl or
      butyl groups are found to orient with the hydrocarbon tails lying parallel to the
      surface, while the hexyl and octyl tails of cations are observed to be oriented
      perpendicular to it. The crossover in the orientational preference matches recent
      observations of surface forces of these liquids.

PMID- 22411765
TI  - Suicide, sport and medicine.

PMID- 22411766
TI  - Good news, bad news: sports matter but occupational and household activity really
      matter - sport and recreation unlikely to be a panacea for public health.

PMID- 22411767
TI  - Opinions and practices of veterinarians and dairy farmers towards herd health
      management in the UK.
AB  - The objective was to compare farm veterinary surgeons' and dairy farmers'
      opinions on herd health plans and herd health and production management with the
      aim of discovering and better understanding the differences. Two comparable
      questionnaires, one for farm veterinarians and one for dairy farmers, were
      distributed throughout the UK. While listing the 'major roles' of the
      veterinarian on the farm, veterinarians considered 'optimising milk production',
      'decreasing overall cost' and 'being an independent adviser' as important roles,
      but these were not seem to be perceived as such by the farmers. In addition, when
      presenting themselves to clients, veterinarians seemed to favour the 'friend of
      the farmer' approach; a much smaller proportion of farmers seemed to prefer this
      approach. The majority of farm respondents (98 of 121; 81 per cent) valued the
      discussions with their veterinarian, and it was apparent from the relatively
      small proportion of veterinarians instigating a discussion on farm (33 of 125; 26
      per cent) that there is the opportunity for a more proactive approach from
      veterinarians. The study underlines that 'demonstrating cost-effectiveness' is
      still a main concern for veterinarians and farmers and identifies areas that can
      be improved by more training and effective communication.

PMID- 22411768
TI  - Solid-vapor sorption of xylenes: prioritized selectivity as a means of separating
      all three isomers using a single substrate.
AB  - A Werner complex is highly selective for o-xylene in a vapor mixture containing
      all three isomers. However, in the absence of o-xylene, the substrate shows
      similar selectivity for m-xylene over p-xylene. Kinetic studies show a different
      trend whereby m-xylene is absorbed most rapidly, implying that thermodynamic
      factors must be responsible for the selectivity.

PMID- 22411769
TI  - Enriching the tapestry: expanding the scope of life course concepts.

PMID- 22411770
TI  - Giving dementia a face? The portrayal of older people with dementia in German
      weekly news magazines between the years 2000 and 2009.
AB  - OBJECTIVES: We investigated photographic depictions of older people with dementia
      in news magazines according to their frequency as well as observable
      characteristics of the characters. METHOD: We examined all 2,604 photos appearing
      in articles identified using the key words "dementia" and "Alzheimer's" published
      in the 4 major German weekly news magazines between 2000 and 2009. According to
      the body text and/or the legend, 154 characters with dementia were identified.
      Trained judges rated the age and gender of each character as well as the
      emotional expression, physical functioning, physical surroundings, and social
      context of the characters. RESULTS: Visual representations of characters with
      dementia linearly increased across time (both in terms of absolute and relative
      figures). Women were shown more often than men. Young-old and old-old characters
      were depicted equally often. Characters were mostly depicted as having positive
      emotions and good functional health. A large majority of characters were shown in
      individualized contexts and together with social partners. Only 2 social partners
      displayed negative emotions, and he/she was a "helper" in less than one third of
      cases. DISCUSSION: Despite the overall low frequency of photos of older people
      with dementia, dementia seems to have "acquired a face" across the past decade.
      Although our analysis revealed a heterogeneous portrayal of older people with
      dementia, "positive" representations clearly prevailed.

PMID- 22411771
TI  - Synthesis of polyethylene containing allene groups: a simple and efficient route
      to functional polyethylene.
AB  - Allene groups are first employed as the reactive moiety in the simple and
      efficient synthesis of well-defined functional polyethylene. By copolymerization
      of ethylene with allene group substituted norbornene, the allene group is
      successfully introduced into the polyethylene with a high content. The retained
      allene groups are demonstrated to be highly reactive in following photoinduced
      functionalized reactions and can be efficiently converted into the functional
      groups without the multi-step, time consuming processes that have generally been
      required in previous reports, providing the side group-functionalized
      polyethylene with a wide range of functional group content.

PMID- 22411772
TI  - Orthographic word knowledge growth in school-age children.
AB  - PURPOSE: Natural reading experiences provide an opportunity for the development
      of orthographic word knowledge as well as other forms of partial word knowledge.
      The purpose of this study was to compare the orthographic word knowledge growth
      of school-age children with relatively low language skills (LL group) to that of
      age- and gender-matched peers with high language skills (HL group). METHOD:
      Thirty-two children, 16 per group, read stories containing rare words 3 times, 2
      3 days apart. Posttesting, completed at the end of each session, required
      participants to indicate recognition of the rare words encountered in the stories
      while not indicating recognition of orthographically similar nonwords. RESULTS:
      Over time, both groups showed significant growth in recognition of the
      orthographic forms of the rare words. However, the groups differed in the extent
      to which they indicated that the orthographically similar nonwords were words,
      with the LL group indicating that significantly more of the nonwords were words.
      CONCLUSION: Results provide some preliminary evidence that children with
      relatively weaker language skills are able to develop orthographic knowledge of
      unfamiliar words through reading experiences, but their orthographic
      representations may not be as well defined as those of children with stronger
      language skills.

PMID- 22411773
TI  - Development of a theoretically based treatment for sentence comprehension
      deficits in individuals with aphasia.
AB  - PURPOSE: Two new treatments, 1 based on sentence to picture matching (SPM) and
      the other on object manipulation (OM), that train participants on the thematic
      roles of sentences using pictures or by manipulating objects were piloted.
      METHOD: Using a single-subject multiple-baseline design, sentence comprehension
      was trained on the affected sentence type in 1 task-related protocol in 15
      participants with aphasia. The 2 tasks were SPM and OM; the treatment stimuli
      were object relatives, object clefts, passives, and unaccusatives, as well as two
      control structures-object relatives with a complex noun phrase (NP) and active
      sentences with three NPs. RESULTS: The criteria for efficacious treatment was an
      increase in the level of performance from the pretreatment probes to the
      posttreatment probes for the treated structure such that accuracy rose from at or
      below chance to above chance and either (a) accuracy rose by 33% or (b) the
      effect size was 2.6. Based on these criteria, the success rate for training the
      target structure was 2/6 participants in the SPM condition and 4/7 participants
      in the OM condition. CONCLUSION: The outcome of this study illustrates the
      utility of this theoretically motivated and efficacious treatment for sentence
      comprehension deficits in individuals with aphasia.

PMID- 22411774
TI  - Training production of lexical stress in typically developing children using
      orthographically biased stimuli and principles of motor learning.
AB  - PURPOSE: Impaired lexical stress production characterizes multiple pediatric
      speech disorders. Effective remediation strategies are not available, and little
      is known about the normal process of learning to assign and produce lexical
      stress. This study examined whether typically developing (TD) children can be
      trained to produce lexical stress on bisyllabic pseudowords that are
      orthographically biased to a strong-weak or weak-strong pattern (e.g.,   MAMbey
      or   beDOON), in combination with the principles of motor learning (PML). METHOD:
      Fourteen TD children ages 5;0 (years;months) to 13;0 were randomly assigned to a
      training or control group using concealed allocation within blocks. A pre- to
      posttraining group design was used to examine the acquisition, retention, and
      generalization of lexical stress production. RESULTS: The training group learned
      to produce appropriate lexical stress for the pseudowords with strong maintenance
      and generalization to related untrained stimuli. Accuracy of stress production
      did not change in the control group. CONCLUSION: TD children can learn to produce
      lexical stress patterns for orthographically biased pseudowords via explicit
      training methods. Findings have relevance for the study of languages other than
      English and for a range of prosodic disorders.

PMID- 22411775
TI  - A sensitive zinc-activated 129Xe MRI probe.

PMID- 22411776
TI  - Poly(ethyleneimine)-mediated large-scale transient gene expression: influence of
      molecular weight, polydispersity and N-propionyl groups.
AB  - Three synthesis lots of linear poly(ethyleneimine) (PEI) are compared to a fully
      hydrolyzed linear PEI (commercially available as PEI "Max") regarding structure,
      polyplex formation with plasmid DNA, and transfection of suspension-adapted HEK
      293E cells. PEI "Max" binds DNA more efficiently than the other PEIs, but it is
      the least effective in terms of transient recombinant protein yield. One PEI lot
      is fractionated by means of SEC. The fractions of high-M(n) PEI are the most
      efficient for complex formation and transfection. Nevertheless, the highest
      transient recombinant protein yields are achieved with unfractionated PEI. The
      results demonstrate that the polydispersity and charge density of linear PEI are
      important parameters for gene delivery to suspension-adapted HEK-293E cells.

PMID- 22411777
TI  - Mass transport at microband electrodes: transient, quasi-steady-state, and
      convective regimes.
AB  - Mass transport at microband electrodes is investigated theoretically and
      experimentally in unstirred solutions by chronoamperometry and cyclic
      voltammetry. Because natural convection limits the convection-free domain up to
      which diffusion layers may only expand, several regimes of mass transport are
      identified through simulation by means of a previous model. A zone diagram is
      established which allows all relative contributions to mass transport to be
      delineated according to the electrode dimension, timescale of experiment, and
      amplitude of natural convection. In opposition to the quasi-steady-state regime
      usually expected at microband electrodes under diffusion control, a steady-state
      regime always occurs at long enough times. By comparison to microdisk electrodes,
      a greater influence of natural convection is predicted. These results are
      validated experimentally by monitoring current responses and mapping steady-state
      concentration profiles at microband electrodes.

PMID- 22411778
TI  - Super-resolution for multislice diffusion tensor imaging.
AB  - Diffusion weighted magnetic resonance images are often acquired with single shot
      multislice imaging sequences, because of their short scanning times and
      robustness to motion. To minimize noise and acquisition time, images are
      generally acquired with either anisotropic or isotropic low resolution voxels,
      which impedes subsequent posterior image processing and visualization. In this
      article, we propose a super-resolution method for diffusion weighted imaging that
      combines anisotropic multislice images to enhance the spatial resolution of
      diffusion tensor data. Each diffusion weighted image is reconstructed from a set
      of arbitrarily oriented images with a low through-plane resolution. The quality
      of the reconstructed diffusion weighted images was evaluated by diffusion tensor
      metrics and tractography. Experiments with simulated data, a hardware DTI
      phantom, as well as in vivo human brain data were conducted. Our results show a
      significant increase in spatial resolution of the diffusion tensor data while
      preserving high signal to noise ratio.

PMID- 22411779
TI  - Rank-based estimate of four-parameter logistic model.
AB  - During drug development, the calculation of inhibitory concentration that results
      in a response of 50% (IC50) is performed thousands of times every day. The
      nonlinear model most often used to perform this calculation is a four-parameter
      logistic, suitably parameterized to estimate the IC50 directly. When performing
      these calculations in a high-throughput mode, each and every curve cannot be
      studied in detail, and outliers in the responses are a common problem. A robust
      estimation procedure to perform this calculation is desirable. In this paper, a
      rank-based estimate of the four-parameter logistic model that is analogous to
      least squares is proposed. The rank-based estimate is based on the Wilcoxon norm.
      The robust procedure is illustrated with several examples from the pharmaceutical
      industry. When no outliers are present in the data, the robust estimate of IC50
      is comparable with the least squares estimate, and when outliers are present in
      the data, the robust estimate is more accurate. A robust goodness-of-fit test is
      also proposed. To investigate the impact of outliers on the traditional and
      robust estimates, a small simulation study was conducted.

PMID- 22411781
TI  - Surface-engineered polyelectrolyte multilayer capsules: synthetic vaccines
      mimicking microbial structure and function.
AB  - Immunizing: to evoke highly potent immune responses against recombinant antigens,
      hollow capsules consisting of layers of dextran sulphate and poly-L-arginine that
      encapsulate the antigen ovalbumin (orange circles) were coated with immune
      activating CpG-containing oligonucleotides (green). These capsules were readily
      internalized by dendritic cells and showed activity in further immunization
      experiments.

PMID- 22411782
TI  - The effects of nanofiber topography on astrocyte behavior and gene silencing
      efficiency.
AB  - Astrocyte-nanofiber interactions are studied by culturing primary rat cortical
      astrocytes on poly[caprolactone-co-(ethyl ethylene phosphate)] electrospun
      nanofibers and solvent-cast films (two-dimensional control). The results indicate
      that nanofiber topography significantly suppresses astrocyte proliferation and
      enhances apoptosis, without altering cellular activation as compared to films.
      Moreover, nanofiber topography enhances gene-silencing efficiency in astrocytes.
      The results suggest that nanofibers may serve as potential substrates for nerve
      regeneration by suppressing astrocyte growth and may further facilitate the use
      of gene-silencing to enhance CNS regeneration.

PMID- 22411783
TI  - The influence of defects on Mo-doped TiO2 by first-principles studies.
AB  - TiO(2) doped with transition metals shows improved photocatalytic efficiency.
      Herein the electronic and optical properties of Mo-doped TiO(2) with defects are
      investigated by DFT calculations. For both rutile and anatase phases of TiO(2),
      the bandgap decreases continuously with increasing Mo doping level. The 4d
      electrons of Mo introduce localized states into the forbidden band of TiO(2), and
      this shifts the absorption edge into the visible-light region and enhances the
      photocatalytic activity. Since defects are universally distributed in TiO(2) or
      doped TiO(2), the effect of oxygen deficiency due to oxygen vacancies or
      interstitial Mo atoms is systemically studied. Oxygen vacancies associated with
      the Mo dopant atoms or interstitial Mo will reduce the spin polarization and
      magnetic moment of Mo-doped TiO(2). Moreover, oxygen deficiency has a negative
      impact on the improved photocatalytic activity of Mo-doped TiO(2). The current
      results indicate that substitutional Mo, interstitial Mo, and oxygen vacancy have
      different impacts on the electronic/optical properties of TiO(2) and are suited
      to different applications.

PMID- 22411785
TI  - Propensity score applied to survival data analysis through proportional hazards
      models: a Monte Carlo study.
AB  - Propensity score methods are increasingly used in medical literature to estimate
      treatment effect using data from observational studies. Despite many papers on
      propensity score analysis, few have focused on the analysis of survival data.
      Even within the framework of the popular proportional hazard model, the choice
      among marginal, stratified or adjusted models remains unclear. A Monte Carlo
      simulation study was used to compare the performance of several survival models
      to estimate both marginal and conditional treatment effects. The impact of
      accounting or not for pairing when analysing propensity-score-matched survival
      data was assessed. In addition, the influence of unmeasured confounders was
      investigated. After matching on the propensity score, both marginal and
      conditional treatment effects could be reliably estimated. Ignoring the paired
      structure of the data led to an increased test size due to an overestimated
      variance of the treatment effect. Among the various survival models considered,
      stratified models systematically showed poorer performance. Omitting a covariate
      in the propensity score model led to a biased estimation of treatment effect, but
      replacement of the unmeasured confounder by a correlated one allowed a marked
      decrease in this bias. Our study showed that propensity scores applied to
      survival data can lead to unbiased estimation of both marginal and conditional
      treatment effect, when marginal and adjusted Cox models are used. In all cases,
      it is necessary to account for pairing when analysing propensity-score-matched
      data, using a robust estimator of the variance.

PMID- 22411784
TI  - On the inherent precision of mcDESPOT.
AB  - A statistical analysis of the mcDESPOT protocol for characterizing two exchanging
      water proton pools--a seven-dimensional problem that fits to multiple flip angle
      measurements of both spoiled and refocused gradient echoes--is presented.
      Theoretical calculations of the Cramer-Rao lower bounds of the variance of fitted
      model parameters were made using a variety of model system parameters, meant to
      mimic those expected in human white matter. The results, validated by Monte Carlo
      simulations, indicated that mcDESPOT signals acquired at feasibly attainable
      signal-to-noise ratios cannot provide parameter estimates with useful levels of
      precision. Precision can be greatly improved by constraining solutions with a
      priori model information, although this will generally lead to biased parameter
      estimates with less specificity. These results indicate that previous, apparently
      successful applications of mcDESPOT to human white matter may have used data
      fitting methods that implicitly constrained parameter solutions, or that the two
      pool model of white matter may not be sufficient to describe the observed water
      proton signal in mcDESPOT acquisitions. In either case, mcDESPOT-derived
      estimates of two-pool model parameters cannot yet be unambiguously related to
      specific tissue characteristics.

PMID- 22411786
TI  - Oil sands mining and reclamation cause massive loss of peatland and stored
      carbon.
AB  - We quantified the wholesale transformation of the boreal landscape by open-pit
      oil sands mining in Alberta, Canada to evaluate its effect on carbon storage and
      sequestration. Contrary to claims made in the media, peatland destroyed by open
      pit mining will not be restored. Current plans dictate its replacement with
      upland forest and tailings storage lakes, amounting to the destruction of over
      29,500 ha of peatland habitat. Landscape changes caused by currently approved
      mines will release between 11.4 and 47.3 million metric tons of stored carbon and
      will reduce carbon sequestration potential by 5,734-7,241 metric tons C/y. These
      losses have not previously been quantified, and should be included with the
      already high estimates of carbon emissions from oil sands mining and bitumen
      upgrading. A fair evaluation of the costs and benefits of oil sands mining
      requires a rigorous assessment of impacts on natural capital and ecosystem
      services.

PMID- 22411787
TI  - Myelin-derived ephrinB3 restricts axonal regeneration and recovery after adult
      CNS injury.
AB  - Recovery of neurological function after traumatic injury of the adult mammalian
      central nervous system is limited by lack of axonal growth. Myelin-derived
      inhibitors contribute to axonal growth restriction, with ephrinB3 being a
      developmentally important axonal guidance cue whose expression in mature
      oligodendrocytes suggests a role in regeneration. Here we explored the in vivo
      regeneration role of ephrinB3 using mice lacking a functional ephrinB3 gene. We
      confirm that ephrinB3 accounts for a substantial portion of detergent-resistant
      myelin-derived inhibition in vitro. To assess in vivo regeneration, we crushed
      the optic nerve and examined retinal ganglion fibers extending past the crush
      site. Significantly increased axonal regeneration is detected in ephrinB3(-/-)
      mice. Studies of spinal cord injury in ephrinB3(-/-) mice must take into account
      altered spinal cord development and an abnormal hopping gait before injury. In a
      near-total thoracic transection model, ephrinB3(-/-) mice show greater spasticity
      than wild-type mice for 2 mo, with slightly greater hindlimb function at later
      time points, but no evidence for axonal regeneration. After a dorsal hemisection
      injury, increased corticospinal and raphespinal growth in the caudal spinal cord
      are detected by 6 wk. This increased axonal growth is accompanied by improved
      locomotor performance measured in the open field and by kinematic analysis. Thus,
      ephrinB3 contributes to myelin-derived axonal growth inhibition and limits
      recovery from adult CNS trauma.

PMID- 22411788
TI  - The Williams syndrome chromosome 7q11.23 hemideletion confers hypersocial,
      anxious personality coupled with altered insula structure and function.
AB  - Although it is widely accepted that genes can influence complex behavioral traits
      such as human temperament, the underlying neurogenetic mechanisms remain unclear.
      Williams syndrome (WS), a rare disorder caused by a hemizygous deletion on
      chromosome 7q11.23, including genes important for neuronal migration and
      maturation (LIMK1 and CLIP2), is typified by a remarkable hypersocial but anxious
      personality and offers a unique opportunity to investigate this open issue. Based
      on the documented role of the insula in mediating emotional response tendencies
      and personality, we used multimodal imaging to characterize this region in WS and
      found convergent anomalies: an overall decrease in dorsal anterior insula (AI)
      gray-matter volume along with locally increased volume in the right ventral AI;
      compromised white-matter integrity of the uncinate fasciculus connecting the
      insula with the amygdala and orbitofrontal cortex; altered regional cerebral
      blood flow in a pattern reminiscent of the observed gray-matter alterations
      (i.e., widespread reductions in dorsal AI accompanied by locally increased
      regional cerebral blood flow in the right ventral AI); and disturbed
      neurofunctional interactions between the AI and limbic regions. Moreover, these
      genetically determined alterations of AI structure and function predicted the
      degree to which the atypical WS personality profile was expressed in participants
      with the syndrome. The AI's rich anatomical connectivity, its transmodal
      properties, and its involvement in the behaviors affected in WS make the observed
      genetically determined insular circuitry perturbations and their association with
      WS personality a striking demonstration of the means by which neural systems can
      serve as the interface between genetic variability and alterations in complex
      behavioral traits.

PMID- 22411789
TI  - Correcting human mitochondrial mutations with targeted RNA import.
AB  - Mutations in the human mitochondrial genome are implicated in neuromuscular
      diseases, metabolic defects, and aging. An efficient and simple mechanism for
      neutralizing deleterious mitochondrial DNA (mtDNA) alterations has unfortunately
      remained elusive. Here, we report that a 20-ribonucleotide stem-loop sequence
      from the H1 RNA, the RNA component of the human RNase P enzyme, appended to a
      nonimported RNA directs the import of the resultant RNA fusion transcript into
      human mitochondria. The methodology is effective for both noncoding RNAs, such as
      tRNAs, and mRNAs. The RNA import component, polynucleotide phosphorylase
      (PNPASE), facilitates transfer of this hybrid RNA into the mitochondrial matrix.
      In addition, nucleus-encoded mRNAs for mitochondrial proteins, such as the mRNA
      of human mitochondrial ribosomal protein S12 (MRPS12), contain regulatory
      sequences in their 3'-untranslated region (UTR) that confers localization to the
      mitochondrial outer membrane, which is postulated to aid in protein translocation
      after translation. We show that for some mitochondrial-encoded transcripts, such
      as COX2, a 3'-UTR localization sequence is not required for mRNA import, whereas
      for corrective mitochondrial-encoded tRNAs, appending the 3'-UTR localization
      sequence was essential for efficient fusion-transcript translocation into
      mitochondria. In vivo, functional defects in mitochondrial RNA (mtRNA)
      translation and cell respiration were reversed in two human disease lines. Thus,
      this study indicates that a wide range of RNAs can be targeted to mitochondria by
      appending a targeting sequence that interacts with PNPASE, with or without a
      mitochondrial localization sequence, providing an exciting, general approach for
      overcoming mitochondrial genetic disorders.

PMID- 22411790
TI  - Late Jurassic salamandroid from western Liaoning, China.
AB  - A Jurassic salamander, Beiyanerpeton jianpingensis (gen. et sp. nov.), from a
      recently found site in western Liaoning Province, China is the earliest known
      record of Salamandroidea. As a Late Jurassic record of the group, it extends the
      range of the clade by ~40 Ma. The Late Jurassic taxon is neotenic and represented
      by exceptionally preserved specimens, including fully articulated cranial and
      postcranial skeletons and bony gill structures close to the cheek region. The
      fossil beds, consisting of dark-brown volcanic ash shales of the Upper Jurassic
      Tiaojishan (Lanqi) Formation (Oxfordian), underlie trachyandesite rocks that have
      yielded a SHRIMP zircon U-Pb date of 157 +/- 3 Ma. The fossiliferous beds are
      substantially older than the Jehol Group, including the Yixian Formation
      ((40)Ar/(39)Ar dates of 122-129 Ma), but slightly younger than the Middle
      Jurassic Daohugou horizon ((40)Ar/(39)Ar date of 164 +/- 4 Ma). The early fossil
      taxon shares with extant salamandroids derived character states, including:
      separated nasals lacking a midline contact, angular fused to the prearticular in
      the lower jaw, and double-headed ribs on the presacral vertebrae. In contrast to
      extant salamandroids, however, the salamander shows a discrete and tooth-bearing
      palatine, and unequivocally nonpedicellate and monocuspid marginal teeth in large
      and presumably mature individuals. The finding provides insights into the
      evolution of key characters of salamanders, and also provides direct evidence
      supporting the hypothesis that the split between Cryptobranchoidea and
      Salamandroidea had taken placed before the Late Jurassic Oxfordian time. In this
      aspect, both paleontological and molecular data now come to agree.

PMID- 22411791
TI  - Regulation of neuroblastoma differentiation by forkhead transcription factors
      FOXO1/3/4 through the receptor tyrosine kinase PDGFRA.
AB  - Neuroblastoma is a common childhood malignant tumor originated from the neural
      crest-derived sympathetic nervous system. A crucial early event in neuroblastoma
      pathogenesis is arrested differentiation of neuroblasts at various stages.
      Treatment of neuroblastoma with TPA and PDGF-BB leads to terminal differentiation
      of neuroblastoma cells. However, the signaling pathways that are involved in this
      process remain largely unknown. Here, we report that inhibition of endogenous
      FOXO proteins attenuated TPA/PDGF-BB mediated differentiation of neuroblastoma
      cells. Activated FOXO transcription factors acted on PDGFRA promoter to direct
      its basal mRNA expression as well as its induction upon serum deprivation.
      Depletion of endogenous PDGFRA in neuroblastoma cells significantly diminished
      neurite formation and extension under TPA/PDGF-BB treatment. Furthermore, ectopic
      expression of PDGFRA abolished the blockage of neuroblastoma differentiation by
      FOXOs inhibition. These findings define the FOXO-PDGFRA axis as crucial
      mechanistic components that govern TPA-induced neuroblastoma differentiation.

PMID- 22411792
TI  - Retraction for Zhong et al. GCK is essential to systemic inflammation and pattern
      recognition receptor signaling to JNK and p38.

PMID- 22411793
TI  - Mutation in a primate-conserved retrotransposon reveals a noncoding RNA as a
      mediator of infantile encephalopathy.
AB  - The human genome is densely populated with transposons and transposon-like
      repetitive elements. Although the impact of these transposons and elements on
      human genome evolution is recognized, the significance of subtle variations in
      their sequence remains mostly unexplored. Here we report homozygosity mapping of
      an infantile neurodegenerative disease locus in a genetic isolate. Complete DNA
      sequencing of the 400-kb linkage locus revealed a point mutation in a primate
      specific retrotransposon that was transcribed as part of a unique noncoding RNA,
      which was expressed in the brain. In vitro knockdown of this RNA increased
      neuronal apoptosis, consistent with the inappropriate dosage of this RNA in vivo
      and with the phenotype. Moreover, structural analysis of the sequence revealed a
      small RNA-like hairpin that was consistent with the putative gain of a functional
      site when mutated. We show here that a mutation in a unique transposable element
      containing RNA is associated with lethal encephalopathy, and we suggest that RNAs
      that harbor evolutionarily recent repetitive elements may play important roles in
      human brain development.

PMID- 22411794
TI  - Hypoxia promotes ligand-independent EGF receptor signaling via hypoxia-inducible
      factor-mediated upregulation of caveolin-1.
AB  - Caveolin-1 (CAV1) is an essential structural constituent of caveolae, specialized
      lipid raft microdomains on the cell membrane involved in endocytosis and signal
      transduction, which are inexplicably deregulated and are associated with
      aggressiveness in numerous cancers. Here we identify CAV1 as a direct
      transcriptional target of oxygen-labile hypoxia-inducible factor 1 and 2 that
      accentuates the formation of caveolae, leading to increased dimerization of EGF
      receptor within the confined surface area of caveolae and its subsequent
      phosphorylation in the absence of ligand. Hypoxia-inducible factor-dependent up
      regulation of CAV1 enhanced the oncogenic potential of tumor cells by increasing
      the cell proliferative, migratory, and invasive capacities. These results support
      a concept in which a crisis in oxygen availability or a tumor exhibiting hypoxic
      signature triggers caveolae formation that bypasses the requirement for ligand
      engagement to initiate receptor activation and the critical downstream adaptive
      signaling during a period when ligands required to activate these receptors are
      limited or are not yet available.

PMID- 22411795
TI  - Postexposure antibody prophylaxis protects nonhuman primates from filovirus
      disease.
AB  - Antibody therapies to prevent or limit filovirus infections have received modest
      interest in recent years, in part because of early negative experimental
      evidence. We have overcome the limitations of this approach, leveraging the use
      of antibody from nonhuman primates (NHPs) that survived challenge to filoviruses
      under controlled conditions. By using concentrated, polyclonal IgG antibody from
      these survivors, we treated filovirus-infected NHPs with multiple doses
      administered over the clinical phase of disease. In the first study, Marburg
      virus (MARV)-infected NHPs were treated 15 to 30 min postexposure with virus
      specific IgG, with additional treatments on days 4 and 8 postexposure. The
      postexposure IgG treatment was completely protective, with no signs of disease or
      detectable viremia. MARV-specific IgM antibody responses were generated, and all
      macaques survived rechallenge with MARV, suggesting that they generated an immune
      response to virus replication. In the next set of studies, NHPs were infected
      with MARV or Ebola virus (EBOV), and treatments were delayed 48 h, with
      additional treatments on days 4 and 8 postexposure. The delayed treatments
      protected both MARV- and EBOV-challenged NHPs. In both studies, two of the three
      IgG-treated NHPs had no clinical signs of illness, with the third NHP developing
      mild and delayed signs of disease followed by full recovery. These studies
      clearly demonstrate that postexposure antibody treatments can protect NHPs and
      open avenues for filovirus therapies for human use using established Food and
      Drug Administration-approved polyclonal or monoclonal antibody technologies.

PMID- 22411796
TI  - Nanoalumina promotes the horizontal transfer of multiresistance genes mediated by
      plasmids across genera.
AB  - Antibiotic resistance is a worldwide public health concern. Conjugative transfer
      between closely related strains or species of bacteria is an important method for
      the horizontal transfer of multidrug-resistance genes. The extent to which
      nanomaterials are able to cause an increase in antibiotic resistance by the
      regulation of the conjugative transfer of antibiotic-resistance genes in
      bacteria, especially across genera, is still unknown. Here we show that
      nanomaterials in water can significantly promote the horizontal conjugative
      transfer of multidrug-resistance genes mediated by the RP4, RK2, and pCF10
      plasmids. Nanoalumina can promote the conjugative transfer of the RP4 plasmid
      from Escherichia coli to Salmonella spp. by up to 200-fold compared with
      untreated cells. We also explored the mechanisms behind this phenomenon and
      demonstrate that nanoalumina is able to induce oxidative stress, damage bacterial
      cell membranes, enhance the expression of mating pair formation genes and DNA
      transfer and replication genes, and depress the expression of global regulatory
      genes that regulate the conjugative transfer of RP4. These findings are important
      in assessing the risk of nanomaterials to the environment, particularly from
      water and wastewater treatment systems, and in the estimation of the effect of
      manufacture and use of nanomaterials on the environment.

PMID- 22411797
TI  - Innovation under cap-and-trade programs.
AB  - Policies incentivizing the private sector to reach its innovative potential in
      "clean" technologies are likely to play a key role in achieving climate
      stabilization. This article explores the relationship between innovation and cap
      and-trade programs (CTPs)--the world's most prominent climate policy instrument-
      through empirical evidence drawn from successful CTPs for sulfur dioxide and
      nitrogen oxide control. The article shows that before trading began for these
      CTPs, analysts overestimated the value of allowances in a pattern suggestive of
      the frequent a priori overestimation of the compliance costs of regulation. When
      lower-than-expected allowance prices were observed, in part because of the
      unexpected range of abatement approaches used in the lead-up to trading,
      emissions sources chose to bank allowances in significant numbers and reassess
      abatement approaches going forward. In addition, commercially oriented inventive
      activity declined for emissions-reducing technologies with a wide range of costs
      and technical characteristics, dropping from peaks before the establishment of
      CTPs to nadirs a few years into trading. This finding is consistent with
      innovators deciding during trading that their research and development
      investments should be reduced, based on assessments of future market conditions
      under the relevant CTPs. The article concludes with a discussion of the results
      and their implications for innovation and climate policy.

PMID- 22411798
TI  - Synaptic evidence for the efficacy of spaced learning.
AB  - The superiority of spaced vs. massed training is a fundamental feature of
      learning. Here, we describe unanticipated timing rules for the production of long
      term potentiation (LTP) in adult rat hippocampal slices that can account for one
      temporal segment of the spaced trials phenomenon. Successive bouts of
      naturalistic theta burst stimulation of field CA1 afferents markedly enhanced
      previously saturated LTP if spaced apart by 1 h or longer, but were without
      effect when shorter intervals were used. Analyses of F-actin-enriched spines to
      identify potentiated synapses indicated that the added LTP obtained with delayed
      theta trains involved recruitment of synapses that were "missed" by the first
      stimulation bout. Single spine glutamate-uncaging experiments confirmed that less
      than half of the spines in adult hippocampus are primed to undergo plasticity
      under baseline conditions, suggesting that intrinsic variability among individual
      synapses imposes a repetitive presentation requirement for maximizing the
      percentage of potentiated connections. We propose that a combination of local
      diffusion from initially modified spines coupled with much later membrane
      insertion events dictate that the repetitions be widely spaced. Thus, the
      synaptic mechanisms described here provide a neurobiological explanation for one
      component of a poorly understood, ubiquitous aspect of learning.

PMID- 22411799
TI  - Nanoparticle delivery in infant lungs.
AB  - The lung surface is an ideal pathway to the bloodstream for nanoparticle-based
      drug delivery. Thus far, research has focused on the lungs of adults, and little
      is known about nanoparticle behavior in the immature lungs of infants. Here,
      using nonlinear dynamical systems analysis and in vivo experimentation in
      developing animals, we show that nanoparticle deposition in postnatally
      developing lungs peaks at the end of bulk alveolation. This finding suggests a
      unique paradigm, consistent with the emerging theory that as alveoli form through
      secondary septation, alveolar flow becomes chaotic and chaotic mixing kicks in,
      significantly enhancing particle deposition. This finding has significant
      implications for the application of nanoparticle-based inhalation therapeutics in
      young children with immature lungs from birth to 2 y of age.

PMID- 22411800
TI  - Autism-like socio-communicative deficits and stereotypies in mice lacking heparan
      sulfate.
AB  - Heparan sulfate regulates diverse cell-surface signaling events, and its roles in
      the development of the nervous system recently have been increasingly uncovered
      by studies using genetic models carrying mutations of genes encoding enzymes for
      its synthesis. On the other hand, the role of heparan sulfate in the
      physiological function of the adult brain has been poorly characterized, despite
      several pieces of evidence suggesting its role in the regulation of synaptic
      function. To address this issue, we eliminated heparan sulfate from postnatal
      neurons by conditionally inactivating Ext1, the gene encoding an enzyme essential
      for heparan sulfate synthesis. Resultant conditional mutant mice show no
      detectable morphological defects in the cytoarchitecture of the brain.
      Remarkably, these mutant mice recapitulate almost the full range of autistic
      symptoms, including impairments in social interaction, expression of stereotyped,
      repetitive behavior, and impairments in ultrasonic vocalization, as well as some
      associated features. Mapping of neuronal activation by c-Fos immunohistochemistry
      demonstrates that neuronal activation in response to social stimulation is
      attenuated in the amygdala in these mice. Electrophysiology in amygdala pyramidal
      neurons shows an attenuation of excitatory synaptic transmission, presumably
      because of the reduction in the level of synaptically localized AMPA-type
      glutamate receptors. Our results demonstrate that heparan sulfate is critical for
      normal functioning of glutamatergic synapses and that its deficiency mediates
      socio-communicative deficits and stereotypies characteristic for autism.

PMID- 22411801
TI  - Cytotoxicity of a Ti(IV) compound is independent of serum proteins.
AB  - Titanium(IV) compounds are excellent anticancer drug candidates, but they have
      yet to find success in clinical applications. A major limitation in developing
      further compounds has been a general lack of understanding of the mechanism
      governing their bioactivity. To determine factors necessary for bioactivity, we
      tested the cytotoxicity of different ligand compounds in conjunction with
      speciation studies and mass spectrometry bioavailability measurements. These
      studies demonstrated that the Ti(IV) compound of N,N'-di(o
      hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) is cytotoxic to A549 lung
      cancer cells, unlike those of citrate and naphthalene-2,3-diolate. Although serum
      proteins are implicated in the activity of Ti(IV) compounds, we found that these
      interactions do not play a role in [TiO(HBED)](-) activity. Subsequent compound
      characterization revealed ligand properties necessary for activity. These
      findings establish the importance of the ligand in the bioactivity of Ti(IV)
      compounds, provides insights for developing next-generation Ti(IV) anticancer
      compounds, and reveal [TiO(HBED)](-) as a unique candidate anticancer compound.

PMID- 22411802
TI  - Resting-state glutamate level in the anterior cingulate predicts blood-oxygen
      level-dependent response to cognitive control.
AB  - The dorsal anterior cingulate cortex (dACC) is a core structure for the governing
      of cognitive control, and recent studies have shown that interindividual
      differences in dACC anatomy are associated with corresponding differences in the
      ability for cognitive control. However, individuals differ not only in anatomical
      features of dACC, but also exhibit substantial variability regarding the
      biochemical characteristics of the dACC. In this study, we combined magnetic
      resonance spectroscopy ((1)H-MRS) and functional magnetic resonance imaging
      (fMRI), finding that interindividual differences of glutamate levels in the dACC
      during resting-state predict the strength of the blood-oxygen level-dependent
      (BOLD) response to a task requiring cognitive control. This relationship was
      observed in the retrosplenial cortex, the orbitofrontal cortex, the inferior
      parietal lobe, and the basal ganglia. More specifically, individuals with low
      resting-state glutamate levels in the dACC showed an increased BOLD response when
      the task demands were high, whereas high-glutamate individuals showed the
      opposite pattern of an increased BOLD response when the task demands were low.
      Thus, we show here that individual variability of glutamate levels is directly
      related to how the brain implements cognitive control.

PMID- 22411803
TI  - Wnt/beta-catenin signaling requires interaction of the Dishevelled DEP domain and
      C terminus with a discontinuous motif in Frizzled.
AB  - Wnt binding to members of the seven-span transmembrane Frizzled (Fz) receptor
      family controls essential cell fate decisions and tissue polarity during
      development and in adulthood. The Fz-mediated membrane recruitment of the
      cytoplasmic effector Dishevelled (Dvl) is a critical step in Wnt/beta-catenin
      signaling initiation, but how Fz and Dvl act together to drive downstream
      signaling events remains largely undefined. Here, we use an Fz peptide-based
      microarray to uncover a mechanistically important role of the bipartite Dvl DEP
      domain and C terminal region (DEP-C) in binding a three-segmented discontinuous
      motif in Fz. We show that cooperative use of two conserved motifs in the third
      intracellular loop and the classic C-terminal motif of Fz is required for DEP-C
      binding and Wnt-induced beta-catenin activation in cultured cells and Xenopus
      embryos. Within the complex, the Dvl DEP domain mainly binds the Fz C-terminal
      tail, whereas a short region at the Dvl C-terminal end is required to bind the Fz
      third loop and stabilize the Fz-Dvl interaction. We conclude that Dvl DEP-C
      binding to Fz is a key event in Wnt-mediated signaling relay to beta-catenin. The
      discontinuous nature of the Fz-Dvl interface may allow for precise regulation of
      the interaction in the control of Wnt-dependent cellular responses.

PMID- 22411804
TI  - In vitro modeling of respiratory syncytial virus infection of pediatric bronchial
      epithelium, the primary target of infection in vivo.
AB  - Respiratory syncytial virus (RSV) is the major viral cause of severe pulmonary
      disease in young infants worldwide. However, the mechanisms by which RSV causes
      disease in humans remain poorly understood. To help bridge this gap, we developed
      an ex vivo/in vitro model of RSV infection based on well-differentiated primary
      pediatric bronchial epithelial cells (WD-PBECs), the primary targets of RSV
      infection in vivo. Our RSV/WD-PBEC model demonstrated remarkable similarities to
      hallmarks of RSV infection in infant lungs. These hallmarks included restriction
      of infection to noncontiguous or small clumps of apical ciliated and occasional
      nonciliated epithelial cells, apoptosis and sloughing of apical epithelial cells,
      occasional syncytium formation, goblet cell hyperplasia/metaplasia, and mucus
      hypersecretion. RSV was shed exclusively from the apical surface at titers
      consistent with those in airway aspirates from hospitalized infants. Furthermore,
      secretion of proinflammatory chemokines such as CXCL10, CCL5, IL-6, and CXCL8
      reflected those chemokines present in airway aspirates. Interestingly, a recent
      RSV clinical isolate induced more cytopathogenesis than the prototypic A2 strain.
      Our findings indicate that this RSV/WD-PBEC model provides an authentic surrogate
      for RSV infection of airway epithelium in vivo. As such, this model may provide
      insights into RSV pathogenesis in humans that ultimately lead to successful RSV
      vaccines or therapeutics.

PMID- 22411806
TI  - Rescue of neuronal migration deficits in a mouse model of fetal Minamata disease
      by increasing neuronal Ca2+ spike frequency.
AB  - In the brains of patients with fetal Minamata disease (FMD), which is caused by
      exposure to methylmercury (MeHg) during development, many neurons are
      hypoplastic, ectopic, and disoriented, indicating disrupted migration,
      maturation, and growth. MeHg affects a myriad of signaling molecules, but little
      is known about which signals are primary targets for MeHg-induced deficits in
      neuronal development. In this study, using a mouse model of FMD, we examined how
      MeHg affects the migration of cerebellar granule cells during early postnatal
      development. The cerebellum is one of the most susceptible brain regions to MeHg
      exposure, and profound loss of cerebellar granule cells is detected in the brains
      of patients with FMD. We show that MeHg inhibits granule cell migration by
      reducing the frequency of somal Ca(2+) spikes through alterations in Ca(2+),
      cAMP, and insulin-like growth factor 1 (IGF1) signaling. First, MeHg slows the
      speed of granule cell migration in a dose-dependent manner, independent of the
      mode of migration. Second, MeHg reduces the frequency of spontaneous Ca(2+)
      spikes in granule cell somata in a dose-dependent manner. Third, a unique in vivo
      live-imaging system for cell migration reveals that reducing the inhibitory
      effects of MeHg on somal Ca(2+) spike frequency by stimulating internal Ca(2+)
      release and Ca(2+) influxes, inhibiting cAMP activity, or activating IGF1
      receptors ameliorates the inhibitory effects of MeHg on granule cell migration.
      These results suggest that alteration of Ca(2+) spike frequency and Ca(2+), cAMP,
      and IGF1 signaling could be potential therapeutic targets for infants with MeHg
      intoxication.

PMID- 22411807
TI  - Multiple organellar RNA editing factor (MORF) family proteins are required for
      RNA editing in mitochondria and plastids of plants.
AB  - RNA editing in plastids and mitochondria of flowering plants changes hundreds of
      selected cytidines to uridines, mostly in coding regions of mRNAs. Specific
      sequences around the editing sites are presumably recognized by up to 200
      pentatricopeptide repeat (PPR) proteins. The here identified family of multiple
      organellar RNA editing factor (MORF) proteins provides additional components of
      the RNA editing machinery in both plant organelles. Two MORF proteins are
      required for editing in plastids; at least two are essential for editing in
      mitochondria. The loss of a MORF protein abolishes or lowers editing at multiple
      sites, many of which are addressed individually by PPR proteins. In plastids,
      both MORF proteins are required for complete editing at almost all sites,
      suggesting a heterodimeric complex. In yeast two-hybrid and pull-down assays,
      MORF proteins can connect to form hetero- and homodimers. Furthermore, MORF
      proteins interact selectively with PPR proteins, establishing a more complex
      editosome in plant organelles than previously thought.

PMID- 22411808
TI  - Learning predator promotes coexistence of prey species in host-parasitoid
      systems.
AB  - Ecological theory suggests that frequency-dependent predation, in which more
      common prey types are disproportionately favored, promotes the coexistence of
      competing prey species. However, many of the earlier empirical studies that
      investigated the effect of frequency-dependent predation were short-term and
      ignored predator-prey dynamics and system persistence. Therefore, we used long
      term observation of population dynamics to test how frequency-dependent predation
      influences the dynamics and coexistence of competing prey species using insect
      laboratory populations. We established two-host-one-parasitoid populations with
      two bruchid beetles, Callosobruchus chinensis and C. maculatus, as the hosts and
      the pteromalid wasp Anisopteromalus calandrae as their common parasitoid. When
      the parasitoid was absent, C. chinensis was competitively excluded in ~20 wk.
      Introducing the parasitoid greatly enhanced the coexistence time to a maximum of
      118 wk. In the replicates of long-lasting coexistence, the two host species C.
      maculatus and C. chinensis exhibited periodic antiphase oscillations. Behavioral
      experiments showed frequency-dependent predation of A. calandrae that was caused
      by learning. Females of A. calandrae learned host-related olfactory cues during
      oviposition and increased their preference for the common host species. Numerical
      simulations showed that parasitoid learning was the essential mechanism that
      promoted persistence in this host-parasitoid system. Our study is an empirical
      demonstration that frequency-dependent predation has an important role in greatly
      enhancing the coexistence of prey populations, suggesting that predator learning
      affects predator-prey population dynamics and shapes biological communities in
      nature.

PMID- 22411809
TI  - Major taste loss in carnivorous mammals.
AB  - Mammalian sweet taste is primarily mediated by the type 1 taste receptor
      Tas1r2/Tas1r3, whereas Tas1r1/Tas1r3 act as the principal umami taste receptor.
      Bitter taste is mediated by a different group of G protein-coupled receptors, the
      Tas2rs, numbering 3 to ~66, depending on the species. We showed previously that
      the behavioral indifference of cats toward sweet-tasting compounds can be
      explained by the pseudogenization of the Tas1r2 gene, which encodes the Tas1r2
      receptor. To examine the generality of this finding, we sequenced the entire
      coding region of Tas1r2 from 12 species in the order Carnivora. Seven of these
      nonfeline species, all of which are exclusive meat eaters, also have
      independently pseudogenized Tas1r2 caused by ORF-disrupting mutations. Fittingly,
      the purifying selection pressure is markedly relaxed in these species with a
      pseudogenized Tas1r2. In behavioral tests, the Asian otter (defective Tas1r2)
      showed no preference for sweet compounds, but the spectacled bear (intact Tas1r2)
      did. In addition to the inactivation of Tas1r2, we found that sea lion Tas1r1 and
      Tas1r3 are also pseudogenized, consistent with their unique feeding behavior,
      which entails swallowing food whole without chewing. The extensive loss of Tas1r
      receptor function is not restricted to the sea lion: the bottlenose dolphin,
      which evolved independently from the sea lion but displays similar feeding
      behavior, also has all three Tas1rs inactivated, and may also lack functional
      bitter receptors. These data provide strong support for the view that loss of
      taste receptor function in mammals is widespread and directly related to feeding
      specializations.

PMID- 22411810
TI  - Governing epidermal homeostasis by coupling cell-cell adhesion to integrin and
      growth factor signaling, proliferation, and apoptosis.
AB  - Cadherin/catenin-based adhesions coordinate cellular growth, survival, migration,
      and differentiation within a tissue by mechanically anchoring cells to their
      neighbors. They also intersect with diverse signaling pathways in development and
      cancer. Although the adhesive functions of adherens junction proteins are well
      characterized, their contribution to other signaling pathways is less well
      understood. Here, we show that ablation of alpha-catenin in the epidermis
      selectively induces apoptosis in suprabasal differentiating keratinocytes while
      sparing basal cell progenitors. This protection from death is coupled to elevated
      focal adhesion signaling, faster migration, and an altered distribution of growth
      factor receptors. We show that simultaneous depletion of alpha-catenin and focal
      adhesion kinase or p21-activated kinase eliminates basal cell protection as well
      as the elevated migration and proliferation of cells. The increased dependency of
      cells upon matrix interactions for their survival when cell-cell adhesions are
      destabilized has important implications for cancer progression and metastasis.

PMID- 22411811
TI  - Plasmodesmata formation and cell-to-cell transport are reduced in decreased size
      exclusion limit 1 during embryogenesis in Arabidopsis.
AB  - In plants, plasmodesmata (PD) serve as channels for micromolecular and
      macromolecular cell-to-cell transport. Based on structure, PD in immature tissues
      are classified into two types, simple and branched (X- and Y-shaped) or twinned.
      The maximum size of molecules capable of PD transport defines PD aperture, known
      as the PD size exclusion limit. Here we report an Arabidopsis mutation, decreased
      size exclusion limit1 (dse1), that exhibits reduced cell-to-cell transport of the
      small (524 Da) fluorescent tracer 8-hydroxypyrene-1,3,6-trisulfonic acid at the
      midtorpedo stage of embryogenesis. Correspondingly, the fraction of X- and Y
      shaped and twinned PD was reduced in dse1 embryos compared with WT embryos at
      this stage, suggesting that the frequency of PD is related to transport
      capability. dse1 is caused by a point mutation in At4g29860 (previously termed
      TANMEI) at the last donor splice site of its transcript, resulting in alternative
      splicing in both the first intron and the last intron. AtDSE1 is a conserved
      eukaryotic 386-aa WD-repeat protein critical for Arabidopsis morphogenesis and
      reproduction. Similar to its homologs in mouse, null mutants are embryo-lethal.
      The weak loss-of-function mutant dse1 exhibits pleiotropic phenotypes, including
      retarded vegetative growth, delayed flowering time, dysfunctional male and female
      organs, and delayed senescence. Finally, silencing of DSE1 in Nicotiana
      benthamiana leaves leads to reduced movement of GFP fused to tobacco mosaic virus
      movement protein. Thus, DSE1 is important for regulating PD transport between
      plant cells.

PMID- 22411812
TI  - Structural basis for the enhanced stability of highly fluorinated proteins.
AB  - Noncanonical amino acids have proved extremely useful for modifying the
      properties of proteins. Among them, extensively fluorinated (fluorous) amino
      acids seem particularly effective in increasing protein stability; however, in
      the absence of structural data, the basis of this stabilizing effect remains
      poorly understood. To address this problem, we solved X-ray structures for three
      small proteins with hydrophobic cores that are packed with either fluorocarbon or
      hydrocarbon side chains and compared their stabilities. Although larger, the
      fluorinated residues are accommodated within the protein with minimal structural
      perturbation, because they closely match the shape of the hydrocarbon side chains
      that they replace. Thus, stability increases seem to be better explained by
      increases in buried hydrophobic surface area that accompany fluorination than by
      specific fluorous interactions between fluorinated side chains. This finding is
      illustrated by the design of a highly fluorinated protein that, by compensating
      for the larger volume and surface area of the fluorinated side chains, exhibits
      similar stability to its nonfluorinated counterpart. These structure-based
      observations should inform efforts to rationally modulate protein function using
      noncanonical amino acids.

PMID- 22411813
TI  - Cancer-associated epithelial cell adhesion molecule (EpCAM; CD326) enables
      epidermal Langerhans cell motility and migration in vivo.
AB  - After activation, Langerhans cells (LC), a distinct subpopulation of epidermis
      resident dendritic cells, migrate from skin to lymph nodes where they regulate
      the magnitude and quality of immune responses initiated by epicutaneously applied
      antigens. Modulation of LC-keratinocyte adhesion is likely to be central to
      regulation of LC migration. LC express high levels of epithelial cell adhesion
      molecule (EpCAM; CD326), a cell-surface protein that is characteristic of some
      epithelia and many carcinomas and that has been implicated in intercellular
      adhesion and metastasis. To gain insight into EpCAM function in a physiologic
      context in vivo, we generated conditional knockout mice with EpCAM-deficient LC
      and characterized them. Epidermis from these mice contained increased numbers of
      LC with normal levels of MHC and costimulatory molecules and T-cell-stimulatory
      activity in vitro. Migration of EpCAM-deficient LC from skin explants was
      inhibited, but chemotaxis of dissociated LC was not. Correspondingly, the ability
      of contact allergen-stimulated, EpCAM-deficient LC to exit epidermis in vivo was
      delayed, and strikingly fewer hapten-bearing LC subsequently accumulated in lymph
      nodes. Attenuated migration of EpCAM-deficient LC resulted in enhanced contact
      hypersensitivity responses as previously described in LC-deficient mice.
      Intravital microscopy revealed reduced translocation and dendrite motility in
      EpCAM-deficient LC in vivo in contact allergen-treated mice. These results
      conclusively link EpCAM expression to LC motility/migration and LC migration to
      immune regulation. EpCAM appears to promote LC migration from epidermis by
      decreasing LC-keratinocyte adhesion and may modulate intercellular adhesion and
      cell movement within in epithelia during development and carcinogenesis in an
      analogous fashion.

PMID- 22411814
TI  - Myeloid leukemia factor is a conserved regulator of RUNX transcription factor
      activity involved in hematopoiesis.
AB  - Defining the function of the genes that, like RUNX1, are deregulated in blood
      cell malignancies represents an important challenge. Myeloid leukemia factors
      (MLFs) constitute a poorly characterized family of conserved proteins whose
      founding member, MLF1, has been associated with acute myeloid leukemia in humans.
      To gain insight into the functions of this family, we investigated the role of
      the Drosophila MLF homolog during blood cell development. Here we report that mlf
      controls the homeostasis of the Drosophila hematopoietic system. Notably, mlf
      participates in a positive feedback loop to fine tune the activity of the RUNX
      transcription factor Lozenge (LZ) during development of the crystal cells, one of
      the two main blood cell lineages in Drosophila. At the molecular level, our data
      in cell cultures and in vivo strongly suggest that MLF controls the number of
      crystal cells by protecting LZ from degradation. Remarkably, it appears that the
      human MLF1 protein can substitute for MLF in the crystal cell lineage. In
      addition, MLF stabilizes the human oncogenic fusion protein RUNX1-ETO and is
      required for RUNX1-ETO-induced blood cell disorders in a Drosophila model of
      leukemia. Finally, using the human leukemic blood cell line Kasumi-1, we show
      that MLF1 depletion impairs RUNX1-ETO accumulation and reduces RUNX1-ETO
      dependent proliferation. Thus, we propose that the regulation of RUNX protein
      levels is a conserved feature of MLF family members that could be critical for
      normal and pathological blood cell development.

PMID- 22411815
TI  - Bacterial rheotaxis.
AB  - The motility of organisms is often directed in response to environmental stimuli.
      Rheotaxis is the directed movement resulting from fluid velocity gradients, long
      studied in fish, aquatic invertebrates, and spermatozoa. Using carefully
      controlled microfluidic flows, we show that rheotaxis also occurs in bacteria.
      Excellent quantitative agreement between experiments with Bacillus subtilis and a
      mathematical model reveals that bacterial rheotaxis is a purely physical
      phenomenon, in contrast to fish rheotaxis but in the same way as sperm rheotaxis.
      This previously unrecognized bacterial taxis results from a subtle interplay
      between velocity gradients and the helical shape of flagella, which together
      generate a torque that alters a bacterium's swimming direction. Because this
      torque is independent of the presence of a nearby surface, bacterial rheotaxis is
      not limited to the immediate neighborhood of liquid-solid interfaces, but also
      takes place in the bulk fluid. We predict that rheotaxis occurs in a wide range
      of bacterial habitats, from the natural environment to the human body, and can
      interfere with chemotaxis, suggesting that the fitness benefit conferred by
      bacterial motility may be sharply reduced in some hydrodynamic conditions.

PMID- 22411816
TI  - Membrane proteins, magic-angle spinning, and in-cell NMR.

PMID- 22411817
TI  - Chance and risk in adaptive evolution.

PMID- 22411820
TI  - Cofactor-specific photochemical function resolved by ultrafast spectroscopy in
      photosynthetic reaction center crystals.
AB  - High-resolution mapping of cofactor-specific photochemistry in photosynthetic
      reaction centers (RCs) from Rhodobacter sphaeroides was achieved by polarization
      selective ultrafast spectroscopy in single crystals at cryogenic temperature. By
      exploiting the fixed orientation of cofactors within crystals, we isolated a
      single transition within the multicofactor manifold, and elucidated the site
      specific photochemical functions of the cofactors associated with the symmetry
      related active A and inactive B branches. Transient spectra associated with the
      initial excited states were found to involve a set of cofactors that differ
      depending upon whether the monomeric bacteriochlorophylls, BChl(A), BChl(B), or
      the special pair bacteriochlorophyll dimer, P, was chosen for excitation.
      Proceeding from these initial excited states, characteristic photochemical
      functions were resolved. Specifically, our measurements provide direct evidence
      for an alternative charge separation pathway initiated by excitation of BChl(A)
      that does not involve P*. Conversely, the initial excited state produced by
      excitation of BChl(B) was found to decay by energy transfer to P. A clear
      sequential kinetic resolution of BChl(A) and the A-side bacteriopheophytin,
      BPh(A), in the electron transfer proceeding from P* was achieved. These
      experiments demonstrate the opportunity to resolve photochemical function of
      individual cofactors within the multicofactor RC complexes using single crystal
      spectroscopy.

PMID- 22411819
TI  - Evidence for type II cells as cells of origin of K-Ras-induced distal lung
      adenocarcinoma.
AB  - Identifying the cells of origin of lung cancer may lead to new therapeutic
      strategies. Previous work has focused upon the putative bronchoalveolar stem cell
      at the bronchioalveolar duct junction as a cancer cell of origin when a codon 12
      K-Ras mutant is induced via adenoviral Cre inhalation. In the present study, we
      use two "knock-in" Cre-estrogen receptor alleles to inducibly express K-RasG12D
      in CC10(+) epithelial cells and Sftpc(+) type II alveolar cells of the adult
      mouse lung. Analysis of these mice identifies type II cells, Clara cells in the
      terminal bronchioles, and putative bronchoalveolar stem cells as cells of origin
      for K-Ras-induced lung hyperplasia. However, only type II cells appear to
      progress to adenocarcinoma.

PMID- 22411821
TI  - Lateral mobility of individual integrin nanoclusters orchestrates the onset for
      leukocyte adhesion.
AB  - Integrins are cell membrane adhesion receptors involved in morphogenesis,
      immunity, tissue healing, and metastasis. A central, yet unresolved question
      regarding the function of integrins is how these receptors regulate both their
      conformation and dynamic nanoscale organization on the membrane to generate
      adhesion-competent microclusters upon ligand binding. Here we exploit the high
      spatial (nanometer) accuracy and temporal resolution of single-dye tracking to
      dissect the relationship between conformational state, lateral mobility, and
      microclustering of the integrin receptor lymphocyte function-associated antigen 1
      (LFA-1) expressed on immune cells. We recently showed that in quiescent
      monocytes, LFA-1 preorganizes in nanoclusters proximal to nanoscale raft
      components. We now show that these nanoclusters are primarily mobile on the cell
      surface with a small (ca. 5%) subset of conformational-active LFA-1 nanoclusters
      preanchored to the cytoskeleton. Lateral mobility resulted crucial for the
      formation of microclusters upon ligand binding and for stable adhesion under
      shear flow. Activation of high-affinity LFA-1 by extracellular Ca(2+) resulted in
      an eightfold increase on the percentage of immobile nanoclusters and cytoskeleton
      anchorage. Although having the ability to bind to their ligands, these active
      nanoclusters failed to support firm adhesion in static and low shear-flow
      conditions because mobility and clustering capacity were highly compromised.
      Altogether, our work demonstrates an intricate coupling between conformation and
      lateral diffusion of LFA-1 and further underscores the crucial role of mobility
      for the onset of LFA-1 mediated leukocyte adhesion.

PMID- 22411822
TI  - Reconfigurable interactions and three-dimensional patterning of colloidal
      particles and defects in lamellar soft media.
AB  - Colloidal systems find important applications ranging from fabrication of
      photonic crystals to direct probing of phenomena typically encountered in atomic
      crystals and glasses. New applications--such as nanoantennas, plasmonic sensors,
      and nanocircuits--pose a challenge of achieving sparse colloidal assemblies with
      tunable interparticle separations that can be controlled at will. We demonstrate
      reconfigurable multiscale interactions and assembly of colloids mediated by
      defects in cholesteric liquid crystals that are probed by means of laser
      manipulation and three-dimensional imaging. We find that colloids attract via
      distance-independent elastic interactions when pinned to the ends of cholesteric
      oily streaks, line defects at which one or more layers are interrupted. However,
      dislocations and oily streaks can also be optically manipulated to induce kinks,
      allowing one to lock them into the desired configurations that are stabilized by
      elastic energy barriers for structural transformation of the particle-connecting
      defects. Under the influence of elastic energy landscape due to these defects,
      sublamellar-sized colloids self-assemble into structures mimicking the cores of
      dislocations and oily streaks. Interactions between these defect-embedded
      colloids can be varied from attractive to repulsive by optically introducing
      dislocation kinks. The reconfigurable nature of defect-particle interactions
      allows for patterning of defects by manipulation of colloids and, in turn,
      patterning of particles by these defects, thus achieving desired colloidal
      configurations on scales ranging from the size of defect core to the sample size.
      This defect-colloidal sculpturing may be extended to other lamellar media,
      providing the means for optically guided self-assembly of mesoscopic composites
      with predesigned properties.

PMID- 22411823
TI  - Two independent switches regulate cytoplasmic dynein's processivity and
      directionality.
AB  - Cytoplasmic dynein is a microtubule-based molecular motor that participates in a
      multitude of cell activities, from cell division to organelle transport. Unlike
      kinesin and myosin, where different tasks are performed by highly specialized
      members of these superfamilies, a single form of the dynein heavy chain is
      utilized for different functions. This versatility demands an extensive
      regulation of motor function. Using an improved application of an optical trap,
      we were now able to demonstrate that cytoplasmic dynein can generate a discrete
      power stroke as well as a processive walk in either direction; i.e., towards the
      plus- or towards the minus-end of a microtubule. Thus, dynein's motor functions
      can be described by four basic modes of motion: processive and nonprocessive
      movement, and movement in the forward and reverse directions. Importantly, these
      four modes of movement can be controlled by two switches. One switch, based on
      phosphate, determines the directionality of movement. The second switch,
      depending on magnesium, converts cytoplasmic dynein from a nonprocessive to a
      processive motor. The two switches can be triggered separately or jointly by
      changing concentrations of phosphate and magnesium in the local environment. The
      control of four modes of movement by two switches has major implications for our
      understanding of the cellular functions and regulation of cytoplasmic dynein.
      Based on recent studies of dynein's structure we are able to draw new conclusions
      on cytoplasmic dynein's stepping mechanism.

PMID- 22411824
TI  - Forecasting sudden changes in environmental pollution patterns.
AB  - The lack of reliable forecasts for the spread of oceanic and atmospheric
      contamination hinders the effective protection of the ecosystem, society, and the
      economy from the fallouts of environmental disasters. The consequences can be
      dire, as evidenced by the Deepwater Horizon oil spill in the Gulf of Mexico in
      2010. We present a methodology to predict major short-term changes in
      environmental contamination patterns, such as oil spills in the ocean and ash
      clouds in the atmosphere. Our approach is based on new mathematical results on
      the objective (frame-independent) identification of key material surfaces that
      drive tracer mixing in unsteady, finite-time flow data. Some of these material
      surfaces, known as Lagrangian coherent structures (LCSs), turn out to admit
      highly attracting cores that lead to inevitable material instabilities even under
      future uncertainties or unexpected perturbations to the observed flow. These LCS
      cores have the potential to forecast imminent shape changes in the contamination
      pattern, even before the instability builds up and brings large masses of water
      or air into motion. Exploiting this potential, the LCS-core analysis developed
      here provides a model-independent forecasting scheme that relies only on already
      observed or validated flow velocities at the time the prediction is made. We use
      this methodology to obtain high-precision forecasts of two major instabilities
      that occurred in the shape of the Deepwater Horizon oil spill. This is achieved
      using simulated surface currents preceding the prediction times and assuming that
      the oil behaves as a passive tracer.

PMID- 22411825
TI  - Soluble oligomerization provides a beneficial fitness effect on destabilizing
      mutations.
AB  - Mutations create the genetic diversity on which selective pressures can act, yet
      also create structural instability in proteins. How, then, is it possible for
      organisms to ameliorate mutation-induced perturbations of protein stability while
      maintaining biological fitness and gaining a selective advantage? Here we used
      site-specific chromosomal mutagenesis to introduce a selected set of mostly
      destabilizing mutations into folA--an essential chromosomal gene of Escherichia
      coli encoding dihydrofolate reductase (DHFR)--to determine how changes in protein
      stability, activity, and abundance affect fitness. In total, 27 E. coli strains
      carrying mutant DHFR were created. We found no significant correlation between
      protein stability and its catalytic activity nor between catalytic activity and
      fitness in a limited range of variation of catalytic activity observed in
      mutants. The stability of these mutants is strongly correlated with their
      intracellular abundance, suggesting that protein homeostatic machinery plays an
      active role in maintaining intracellular concentrations of proteins. Fitness also
      shows a significant correlation with intracellular abundance of soluble DHFR in
      cells growing at 30  degrees C. At 42  degrees C, the picture was mixed, yet
      remarkable: A few strains carrying mutant DHFR proteins aggregated, rendering
      them nonviable, but, intriguingly, the majority exhibited fitness higher than
      wild type. We found that mutational destabilization of DHFR proteins in E. coli
      is counterbalanced at 42  degrees C by their soluble oligomerization, thereby
      restoring structural stability and protecting against aggregation.

PMID- 22411827
TI  - Supernova-driven outflows and chemical evolution of dwarf spheroidal galaxies.
AB  - We present a general phenomenological model for the metallicity distribution (MD)
      in terms of [Fe/H] for dwarf spheroidal galaxies (dSphs). These galaxies appear
      to have stopped accreting gas from the intergalactic medium and are fossilized
      systems with their stars undergoing slow internal evolution. For a wide variety
      of infall histories of unprocessed baryonic matter to feed star formation, most
      of the observed MDs can be well described by our model. The key requirement is
      that the fraction of the gas mass lost by supernova-driven outflows is close to
      unity. This model also predicts a relationship between the total stellar mass and
      the mean metallicity for dSphs in accord with properties of their dark matter
      halos. The model further predicts as a natural consequence that the abundance
      ratios [E/Fe] for elements such as O, Mg, and Si decrease for stellar populations
      at the higher end of the [Fe/H] range in a dSph. We show that, for infall rates
      far below the net rate of gas loss to star formation and outflows, the MD in our
      model is very sharply peaked at one [Fe/H] value, similar to what is observed in
      most globular clusters. This result suggests that globular clusters may be end
      members of the same family as dSphs.

PMID- 22411826
TI  - Metabolic labeling enables selective photocrosslinking of O-GlcNAc-modified
      proteins to their binding partners.
AB  - O-linked beta-N-acetylglucosamine (O-GlcNAc) is a reversible posttranslational
      modification found on hundreds of nuclear and cytoplasmic proteins in higher
      eukaryotes. Despite its ubiquity and essentiality in mammals, functional roles
      for the O-GlcNAc modification remain poorly defined. Here we develop a combined
      genetic and chemical approach that enables introduction of the diazirine
      photocrosslinker onto the O-GlcNAc modification in cells. We engineered mammalian
      cells to produce diazirine-modified O-GlcNAc by expressing a mutant form of UDP
      GlcNAc pyrophosphorylase and subsequently culturing these cells with a cell
      permeable, diazirine-modified form of GlcNAc-1-phosphate. Irradiation of cells
      with UV light activated the crosslinker, resulting in formation of covalent bonds
      between O-GlcNAc-modified proteins and neighboring molecules, which could be
      identified by mass spectrometry. We used this method to identify interaction
      partners for the O-GlcNAc-modified FG-repeat nucleoporins. We observed
      crosslinking between FG-repeat nucleoporins and nuclear transport factors,
      suggesting that O-GlcNAc residues are intimately associated with essential
      recognition events in nuclear transport. Further, we propose that the method
      reported here could find widespread use in investigating the functional
      consequences of O-GlcNAcylation.

PMID- 22411828
TI  - Structure of the ZU5-ZU5-UPA-DD tandem of ankyrin-B reveals interaction surfaces
      necessary for ankyrin function.
AB  - Ankyrin-R/B/G (encoded by ANK1/2/3, respectively) are a family of very large
      scaffold proteins capable of anchoring numerous receptors and ion channels to
      specific, spectrin-containing membrane micro-domains. Hereditary mutations of
      ankyrins are known to be associated with diseases including spherocytosis,
      cardiac arrhythmia, and bipolar disorder in humans, although the underlying
      molecular bases are poorly understood. The middle spectrin-binding domain of
      ankyrins contains highly conserved ZU5-ZU5-UPA-DD domains arranged into the ZZUD
      tandem. Curiously, most of the disease-causing mutations in the tandem have no
      apparent impact on the spectrin binding of ankyrins. The high resolution
      structure of the ankyrin-B ZZUD tandem determined here reveals that the ZU5-ZU5
      UPA domains form a tightly packed structural supramodule, whereas DD is freely
      accessible. Although the formation of the ZZU supramodule does not influence the
      spectrin binding of ankyrins, mutations altering the interdomain interfaces of
      ZZU impair the functions of ankyrin-B&G. Our structural analysis further
      indicates that the ZZU supramodule of ankyrins has two additional surfaces that
      may bind to targets other than spectrin. Finally, the structure of the ankyrin
      ZZUD provides mechanistic explanations to many disease-causing mutations
      identified in ankyrin-B&R.

PMID- 22411829
TI  - M phase phosphorylation of the epigenetic regulator UHRF1 regulates its physical
      association with the deubiquitylase USP7 and stability.
AB  - UHRF1 (Ubiquitin-like, with PHD and RING finger domains 1) plays an important
      role in DNA CpG methylation, heterochromatin function and gene expression.
      Overexpression of UHRF1 has been suggested to contribute to tumorigenesis.
      However, regulation of UHRF1 is largely unknown. Here we show that the
      deubiquitylase USP7 interacts with UHRF1. Using interaction-defective and
      catalytic mutants of USP7 for complementation experiments, we demonstrate that
      both physical interaction and catalytic activity of USP7 are necessary for UHRF1
      ubiquitylation and stability regulation. Mass spectrometry analysis identified
      phosphorylation of serine (S) 652 within the USP7-interacting domain of UHRF1,
      which was further confirmed by a UHRF1 S652 phosphor (S652ph)-specific antibody.
      Importantly, the S652ph antibody identifies phosphorylated UHRF1 in mitotic cells
      and consistently S652 can be phosphorylated by the M phase-specific kinase CDK1
      cyclin B in vitro. UHRF1 S652 phosphorylation significantly reduces UHRF1
      interaction with USP7 in vitro and in vivo, which is correlated with a decreased
      UHRF1 stability in the M phase of the cell cycle. In contrast, UHRF1 carrying the
      S652A mutation, which renders UHRF1 resistant to phosphorylation at S652, is more
      stable. Importantly, cells carrying the S652A mutant grow more slowly suggesting
      that maintaining an appropriate level of UHRF1 is important for cell
      proliferation regulation. Taken together, our findings uncovered a cell cycle
      specific signaling event that relieves UHRF1 from its interaction with USP7, thus
      exposing UHRF1 to proteasome-mediated degradation. These findings identify a
      molecular mechanism by which cellular UHRF1 level is regulated, which may impact
      cell proliferation.

PMID- 22411830
TI  - A sulfated carbohydrate epitope inhibits axon regeneration after injury.
AB  - Chondroitin sulfate proteoglycans (CSPGs) represent a major barrier to
      regenerating axons in the central nervous system (CNS), but the structural
      diversity of their polysaccharides has hampered efforts to dissect the structure
      activity relationships underlying their physiological activity. By taking
      advantage of our ability to chemically synthesize specific oligosaccharides, we
      demonstrate that a sugar epitope on CSPGs, chondroitin sulfate-E (CS-E), potently
      inhibits axon growth. Removal of the CS-E motif significantly attenuates the
      inhibitory activity of CSPGs on axon growth. Furthermore, CS-E functions as a
      protein recognition element to engage receptors including the transmembrane
      protein tyrosine phosphatase PTPsigma, thereby triggering downstream pathways
      that inhibit axon growth. Finally, masking the CS-E motif using a CS-E-specific
      antibody reversed the inhibitory activity of CSPGs and stimulated axon
      regeneration in vivo. These results demonstrate that a specific sugar epitope
      within chondroitin sulfate polysaccharides can direct important physiological
      processes and provide new therapeutic strategies to regenerate axons after CNS
      injury.

PMID- 22411831
TI  - Reactive polymer enables efficient in vivo bioorthogonal chemistry.
AB  - There has been intense interest in the development of selective bioorthogonal
      reactions or "click" chemistry that can proceed in live animals. Until now
      however, most reactions still require vast surpluses of reactants because of
      steep temporal and spatial concentration gradients. Using computational modeling
      and design of pharmacokinetically optimized reactants, we have developed a
      predictable method for efficient in vivo click reactions. Specifically, we show
      that polymer modified tetrazines (PMT) are a key enabler for in vivo
      bioorthogonal chemistry based on the very fast and catalyst-free [4 + 2]
      tetrazine/trans-cyclooctene cycloaddition. Using fluorescent PMT for cellular
      resolution and (18)F labeled PMT for whole animal imaging, we show that cancer
      cell epitopes can be easily reacted in vivo. This generic strategy should help
      guide the design of future chemistries and find widespread use for different in
      vivo bioorthogonal applications, particularly in the biomedical sciences.

PMID- 22411832
TI  - Selective esterase-ester pair for targeting small molecules with cellular
      specificity.
AB  - Small molecules are important tools to measure and modulate intracellular
      signaling pathways. A longstanding limitation for using chemical compounds in
      complex tissues has been the inability to target bioactive small molecules to a
      specific cell class. Here, we describe a generalizable esterase-ester pair
      capable of targeted delivery of small molecules to living cells and tissue with
      cellular specificity. We used fluorogenic molecules to rapidly identify a small
      ester masking motif that is stable to endogenous esterases, but is efficiently
      removed by an exogenous esterase. This strategy allows facile targeting of dyes
      and drugs in complex biological environments to label specific cell types,
      illuminate gap junction connectivity, and pharmacologically perturb distinct
      subsets of cells. We expect this approach to have general utility for the
      specific delivery of many small molecules to defined cellular populations.

PMID- 22411833
TI  - Initiation factor 2, tRNA, and 50S subunits cooperatively stabilize mRNAs on the
      ribosome during initiation.
AB  - Initiation factor 2 (IF2) is a key factor in initiation of bacterial protein
      synthesis. It recruits initiator tRNA to the small ribosomal subunit and
      facilitates joining of the large ribosomal subunit. Using reconstituted
      translation system of Escherichia coli and optical tweezers, we directly measure
      the rupture force between single ribosomal complexes and mRNAs for initiation
      complexes in the presence and the absence of IF2. We demonstrate that IF2
      together with codon recognition by initiator tRNA increases the force required to
      dislocate mRNA from the ribosome complexes; mRNA stabilization by IF2 required
      the presence of a joined 50S subunit, and was independent of bound guanine
      nucleotide. IF2 thus helps lock the 70S ribosome over the start codon during
      initiation, thus maintaining reading frame. Our results show how mRNA is
      progressively stabilized on the ribosome through distinct steps of initiation.

PMID- 22411834
TI  - Probing the timescale of the exchange interaction in a ferromagnetic alloy.
AB  - The underlying physics of all ferromagnetic behavior is the cooperative
      interaction between individual atomic magnetic moments that results in a
      macroscopic magnetization. In this work, we use extreme ultraviolet pulses from
      high-harmonic generation as an element-specific probe of ultrafast, optically
      driven, demagnetization in a ferromagnetic Fe-Ni alloy (permalloy). We show that
      for times shorter than the characteristic timescale for exchange coupling, the
      magnetization of Fe quenches more strongly than that of Ni. Then as the Fe
      moments start to randomize, the strong ferromagnetic exchange interaction induces
      further demagnetization in Ni, with a characteristic delay determined by the
      strength of the exchange interaction. We can further enhance this delay by
      lowering the exchange energy by diluting the permalloy with Cu. This measurement
      probes how the fundamental quantum mechanical exchange coupling between Fe and Ni
      in magnetic materials influences magnetic switching dynamics in ferromagnetic
      materials relevant to next-generation data storage technologies.

PMID- 22411835
TI  - Posttranslational modifications of Rab proteins cause effective displacement of
      GDP dissociation inhibitor.
AB  - Intracellular vesicular trafficking is regulated by approximately 60 members of
      the Rab subfamily of small Ras-like GDP/GTP binding proteins. Rab proteins cycle
      between inactive and active states as well as between cytosolic and membrane
      bound forms. Membrane extraction/delivery and cytosolic distribution of Rabs is
      mediated by interaction with the protein GDP dissociation inhibitor (GDI) that
      binds to prenylated inactive (GDP-bound) Rab proteins. Because the Rab:GDP:GDI
      complex is of high affinity, the question arises of how GDI can be displaced
      efficiently from Rab protein in order to allow the necessary recruitment of the
      Rab to its specific target membrane. While there is strong evidence that DrrA, as
      a bacterially encoded GDP/GTP exchange factor, contributes to this event, we show
      here that posttranslational modifications of Rabs can also modulate the affinity
      for GDI and thus cause effective displacement of GDI from Rab:GDI complexes.
      These activities have been found associated with the phosphocholination and
      adenylylation activities of the enzymes AnkX and DrrA/SidM, respectively, from
      the pathogenic bacterium Legionella pneumophila. Both modifications occur after
      spontaneous dissociation of Rab:GDI complexes within their natural equilibrium.
      Therefore, the effective GDI displacement that is observed is caused by
      inhibition of reformation of Rab:GDI complexes. Interestingly, in contrast to
      adenylylation by DrrA, AnkX can covalently modify inactive Rabs with high
      catalytic efficiency even when GDP is bound to the GTPase and hence can inhibit
      binding of GDI to Rab:GDP complexes. We therefore speculate that human cells
      could employ similar mechanisms in the absence of infection to effectively
      displace Rabs from GDI.

PMID- 22411836
TI  - Tfb6, a previously unidentified subunit of the general transcription factor
      TFIIH, facilitates dissociation of Ssl2 helicase after transcription initiation.
AB  - General transcription factor TFIIH, previously described as a 10-subunit complex,
      is essential for transcription and DNA repair. An eleventh subunit now
      identified, termed Tfb6, exhibits 45% sequence similarity to human nuclear mRNA
      export factor 5. Tfb6 dissociates from TFIIH as a heterodimer with the Ssl2
      subunit, a DNA helicase that drives promoter melting for the initiation of
      transcription. Tfb6 does not, however, dissociate Ssl2 from TFIIH in the context
      of a fully assembled transcription preinitiation complex. Our findings suggest a
      dynamic state of Ssl2, allowing its engagement in multiple cellular processes.

PMID- 22411837
TI  - Signal transducer and activator of transcription-3/suppressor of cytokine
      signaling-3 (STAT3/SOCS3) axis in myeloid cells regulates neuroinflammation.
AB  - Suppressor of cytokine signaling (SOCS) proteins are feedback inhibitors of the
      JAK/STAT pathway. SOCS3 has a crucial role in inhibiting STAT3 activation,
      cytokine signaling, and inflammatory gene expression in macrophages/microglia. To
      determine the role of SOCS3 in myeloid cells in neuroinflammation, mice with
      conditional SOCS3 deletion in myeloid cells (LysMCre-SOCS3(fl/fl)) were tested
      for experimental autoimmune encephalomyelitis (EAE). The myeloid-specific SOCS3
      deficient mice are vulnerable to myelin oligodendrocyte glycoprotein (MOG)
      induced EAE, with a severe, nonresolving atypical form of disease. In vivo,
      enhanced infiltration of inflammatory cells and demyelination is prominent in the
      cerebellum of myeloid-specific SOCS3-deficient mice, as is enhanced STAT3
      signaling and expression of inflammatory cytokines/chemokines and an immune
      response dominated by Th1 and Th17 cells. In vitro, SOCS3-deficient macrophages
      exhibit heightened STAT3 activation and are polarized toward the classical M1
      phenotype. SOCS3-deficient M1 macrophages provide the microenvironment to
      polarize Th1 and Th17 cells and induce neuronal death. Furthermore, adoptive
      transfer of M2 macrophages into myeloid SOCS3-deficient mice leads to delayed
      onset and reduced severity of atypical EAE by decreasing STAT3 activation,
      Th1/Th17 cells, and proinflammatory mediators in the cerebellum. These findings
      indicate that myeloid cell SOCS3 provides protection from EAE through
      deactivation of neuroinflammatory responses.

PMID- 22411838
TI  - High expression of lactotriaosylceramide, a differentiation-associated
      glycosphingolipid, in the bone marrow of acute myeloid leukemia patients.
AB  - Glycosphingolipids (GSLs) are information-bearing biomolecules that play critical
      roles in embryonic development, signal transduction and carcinogenesis. Previous
      studies indicate that certain GSLs are associated with differentiation in acute
      myeloid leukemia (AML) cells. In this study, we collected bone marrow samples
      from healthy donors and AML patients and analyzed the GSL expression profiles
      comprehensively using electrospray ionization linear ion-trap mass spectrometry.
      The results showed that AML patients had higher expression of the GSL
      lactotriaosylceramide (Lc3), GM3 and neolactotetraosylceramide (nLc4) in their
      bone marrow than did the healthy donors (P < 0.05), especially the M1 subtype of
      AML. To further explore the molecular mechanisms of Lc3, we examined the
      expression of the Lc3 synthase beta1,3-N-acetylglucosaminyltransferase5 (beta3Gn
      T5) and found that the bone marrow samples of AML patients had 16-fold higher
      expression of beta3Gn-T5 than those of healthy donors (P < 0.05). Our results
      suggest that AML-associated GSLs Lc3, GM3 and nLc4 are possibly involved in
      initiation and differentiation of AML.

PMID- 22411839
TI  - Adaptive designs for single-arm phase II trials in oncology.
AB  - Clinical phase II trials in oncology are conducted to determine whether the
      activity of a new anticancer treatment is promising enough to merit further
      investigation. Two-stage designs are commonly used for this situation to allow
      for early termination. Designs proposed in the literature so far have the common
      drawback that the sample sizes for the two stages have to be specified in the
      protocol and have to be adhered to strictly during the course of the trial. As a
      consequence, designs that allow a higher extent of flexibility are desirable. In
      this article, we propose a new adaptive method that allows an arbitrary
      modification of the sample size of the second stage using the results of the
      interim analysis or external information while controlling the type I error rate.
      If the sample size is not changed during the trial, the proposed design shows
      very similar characteristics to the optimal two-stage design proposed by Chang et
      al. (Biometrics 1987; 43:865-874). However, the new design allows the use of mid
      course information for the planning of the second stage, thus meeting practical
      requirements when performing clinical phase II trials in oncology.

PMID- 22411840
TI  - Recognition of aromatic compounds by pi pocket within a cage-shaped borate
      catalyst.
AB  - Taking shape: the ability of a Lewis acid catalyst to distinguish between
      aromatic and aliphatic hydrocarbon moieties was accomplished by using cage-shaped
      borate catalysts B(OC(6)H(3)Aryl)(3)CH having a pi pocket derived from aryl
      substituents surrounding the boron center. The catalyst predominantly activated
      aromatic aldehydes over aliphatic ones for reaction.

PMID- 22411841
TI  - Surface-enhanced Raman scattering (SERS) of nitrothiophenol isomers chemisorbed
      on TiO2.
AB  - Surface-enhanced Raman scattering (SERS) spectroscopy and density functional
      theory (DFT) calculations were used to investigate the nature of the charge
      transfer (CT) process between nitrothiophenol (NTP) isomers and the n-type
      semiconductor, TiO(2). The Raman signals of p-NTP and m-NTP that were chemisorbed
      onto TiO(2) were significantly enhanced with respect to their corresponding neat
      compounds. In particular, an enhancement factor (EF) of 10(2)-10(3) was observed
      for both p-NTP and m-NTP, with m-NTP displaying a larger EF compared to p-NTP.
      The Raman signal of o-NTP on TiO(2) was not detectable, owing to interference
      from fluorescence emissions. A molecule-to-TiO(2) charge-transfer mechanism was
      responsible for the enhanced Raman signals observed in p-NTP and m-NTP. This
      transfer was due to a strong coupling between the adsorbate and the metal oxide,
      which led to an optically driven CT transition from the HOMO of NTP into the
      conduction band of TiO(2). Based on the mesomeric effect, the NO(2) group para to
      the thiol had a stronger electron-withdrawing ability than the NO(2) group at the
      meta position. A less-efficient CT transition from p-NTP to TiO(2) in the surface
      complex resulted in a weaker Raman-signal enhancement for p-NTP compared to m
      NTP. The DFT calculation determined that the HOMO and the LUMO of NTP bound to
      TiO(2) were located entirely on the adsorbate and the semiconductor,
      respectively, thereby supporting the experimental findings that a molecule-to
      TiO(2) mechanism was the driving force behind the observed SERS effect.

PMID- 22411842
TI  - Cardiac arterial spin labeling using segmented ECG-gated Look-Locker FAIR:
      variability and repeatability in preclinical studies.
AB  - MRI is important for the assessment of cardiac structure and function in
      preclinical studies of cardiac disease. Arterial spin labeling techniques can be
      used to measure perfusion noninvasively. In this study, an electrocardiogram
      gated Look-Locker sequence with segmented k-space acquisition has been
      implemented to acquire single slice arterial spin labeling data sets in 15 min in
      the mouse heart. A data logger was introduced to improve data quality by: (1)
      allowing automated rejection of respiration-corrupted images, (2) providing
      additional prospective gating to improve consistency of acquisition timing, and
      (3) allowing the recombination of uncorrupted k-space lines from consecutive data
      sets to reduce respiration corruption. Finally, variability and repeatability of
      perfusion estimation within-session, between-session, between-animal, and between
      image rejection criteria were assessed in mice. The criterion used to reject
      images from the T(1) fit was shown to affect the perfusion estimation. These data
      showed that the between-animal coefficient of variability (24%) was greater than
      the between-session variability (17%) and within-session variability (11%).
      Furthermore, the magnitude of change in perfusion required to detect differences
      was 30% (within-session) and 55% (between-session) according to Bland-Altman
      repeatability analysis. These technique developments and repeatability statistics
      will provide a platform for future preclinical studies applying cardiac arterial
      spin labeling.

PMID- 22411843
TI  - Pyridine-modified acridine-based bipolar host material for green phosphorescent
      organic light-emitting diodes.

PMID- 22411844
TI  - Is executive control used to compensate for involuntary movements in levodopa
      induced dyskinesia?

PMID- 22411845
TI  - Technical advances in deep brain stimulation: how far is enough?

PMID- 22411846
TI  - Bilateral cerebellar stroke presenting with acute dysphonia and late palatal
      tremor.

PMID- 22411847
TI  - Commentary on "Bilateral cerebellar stroke presenting with acute dysphonia and
      late palatal tremor".

PMID- 22411848
TI  - Deep brain stimulation of the subthalamic nucleus improves sense of well-being in
      Parkinson's disease.
AB  - Deep brain stimulation of the subthalamic nucleus is an effective treatment for
      the motor symptoms of Parkinson's disease. Although a range of psychiatric and
      behavioral problems have been documented following deep brain stimulation, the
      short-term effects of subthalamic nucleus stimulation on patients' mood have only
      been investigated in a few studies. Our aim was to compare self-reported mood in
      Parkinson's patients with deep brain stimulation of the subthalamic nucleus ON
      versus OFF. Twenty-three Parkinson's patients with bilateral deep brain
      stimulation of the subthalamic nucleus and 11 unoperated Parkinson's patients
      completed a mood visual analogue scale twice. Operated patients were tested with
      deep brain stimulation of the subthalamic nucleus both ON and OFF. All were
      assessed on medication. The operated Parkinson's group reported feeling
      significantly better coordinated, stronger, and more contented with deep brain
      stimulation ON compared to OFF. Fourteen of the 16 mood scales changed in a
      positive direction when deep brain stimulation of the subthalamic nucleus was ON.
      When changes in motor scores were taken into account, the operated patients still
      reported feeling better-coordinated, but also less gregarious with stimulation
      ON. Unoperated Parkinson's patients showed no differences on any of these
      measures between their 2 ratings. Short-term changes in deep brain stimulation of
      the subthalamic nucleus have a small and mostly positive effect on mood, which
      may be partly related to improvements in motor symptoms. The implications for day
      to-day management of patients with deep brain stimulation of the subthalamic
      nucleus are discussed.

PMID- 22411849
TI  - Erythropoietin in Friedreich ataxia: no effect on frataxin in a randomized
      controlled trial.
AB  - BACKGROUND: Friedreich ataxia is a rare disease caused by GAA-trinucleotide
      repeat expansions in the frataxin gene, leading to marked reduction of
      qualitatively normal frataxin protein. Recently, human recombinant erythropoietin
      was reported to increase frataxin levels in patients with Friedreich ataxia.
      METHODS: We performed a 6-month, randomized placebo-controlled, double-blind,
      dose-response pilot trial to assess the safety and efficacy of erythropoietin in
      increasing frataxin levels. Sixteen adult patient with Friedreich ataxia were
      randomly assigned to erythropoietin (n = 11) or matching placebo (n = 5). All
      patients continued Idebenone treatment (5 mg/kg/day). Treatment consisted of a 6
      month scaling-up phase, in which erythropoietin was administered intravenously at
      the following doses: 20,000 IU every 3 weeks, 40,000 IU every 3 weeks, and 40,000
      IU every 2 weeks. RESULTS: Erythropoietin treatment was safe and well tolerated,
      but did not result in any significant hematological, clinical, or biochemical
      effects in Friedreich ataxia patients.

PMID- 22411850
TI  - A concise and versatile double-cyclization strategy for the highly
      stereoselective synthesis and arylative dimerization of Aspidosperma alkaloids.

PMID- 22411851
TI  - Preparation of [Al(hfip)4](-)-based ionic liquids with siloxane-functionalized
      cations and their physical properties in comparison with their [Tf2N]- analogues.
AB  - Two new ionic liquids (ILs) with siloxane-functionalized cations and the weakly
      coordinating tetraalkoxyaluminate [Al(hfip)(4)](-) (hfip=hexafluoroisopropoxy)
      are prepared and characterized by nuclear magnetic resonance (NMR), infrared (IR)
      and Raman spectroscopy. With melting points below 0  degrees C they qualify as
      room temperature ILs (RTILs). Their temperature-dependent viscosities and
      conductivities, together with those of two [Tf(2)N](-) ILs with the same cations
      and a further siloxane-functionalized [Tf(2)N](-) IL, are measured between 0 and
      80  degrees C, and all are described by the Vogel-Fulcher-Tammann (VFT)
      equations. We note that the [Al(hfip)(4)](-) ILs have lower viscosities than
      their [Tf(2)N](-) analogues at all measured temperatures and higher
      conductivities at room temperature.

PMID- 22411852
TI  - Group I intron-mediated trans-splicing in mitochondria of Gigaspora rosea and a
      robust phylogenetic affiliation of arbuscular mycorrhizal fungi with
      Mortierellales.
AB  - Gigaspora rosea is a member of the arbuscular mycorrhizal fungi (AMF;
      Glomeromycota) and a distant relative of Glomus species that are beneficial to
      plant growth. To allow for a better understanding of Glomeromycota, we have
      sequenced the mitochondrial DNA of G. rosea. A comparison with Glomus
      mitochondrial genomes reveals that Glomeromycota undergo insertion and loss of
      mitochondrial plasmid-related sequences and exhibit considerable variation in
      introns. The gene order between the two species is almost completely reshuffled.
      Furthermore, Gigaspora has fragmented cox1 and rns genes, and an unorthodox
      initiator tRNA that is tailored to decoding frequent UUG initiation codons. For
      the fragmented cox1 gene, we provide evidence that its RNA is joined via group I
      mediated trans-splicing, whereas rns RNA remains in pieces. According to our
      model, the two cox1 precursor RNA pieces are brought together by flanking cox1
      exon sequences that form a group I intron structure, potentially in conjunction
      with the nad5 intron 3 sequence. Finally, we present analyses that address the
      controversial phylogenetic association of Glomeromycota within fungi. According
      to our results, Glomeromycota are not a separate group of paraphyletic
      zygomycetes but branch together with Mortierellales, potentially also
      Harpellales.

PMID- 22411853
TI  - Evidence of pre-Roman tribal genetic structure in Basques from uniparentally
      inherited markers.
AB  - Basque people have received considerable attention from anthropologists,
      geneticists, and linguists during the last century due to the singularity of
      their language and to other cultural and biological characteristics. Despite the
      multidisciplinary efforts performed to address the questions of the origin,
      uniqueness, and heterogeneity of Basques, the genetic studies performed up to now
      have suffered from a weak study design where populations are not analyzed in an
      adequate geographic and population context. To address the former questions and
      to overcome these design limitations, we have analyzed the uniparentally
      inherited markers (Y chromosome and mitochondrial DNA) of ~900 individuals from
      18 populations, including those where Basque is currently spoken and populations
      from adjacent regions where Basque might have been spoken in historical times.
      Our results indicate that Basque-speaking populations fall within the genetic
      Western European gene pool, that they are similar to geographically surrounding
      non-Basque populations, and also that their genetic uniqueness is based on a
      lower amount of external influences compared with other Iberians and French
      populations. Our data suggest that the genetic heterogeneity and structure
      observed in the Basque region result from pre-Roman tribal structure related to
      geography and might be linked to the increased complexity of emerging societies
      during the Bronze Age. The rough overlap of the pre-Roman tribe location and the
      current dialect limits support the notion that the environmental diversity in the
      region has played a recurrent role in cultural differentiation and ethnogenesis
      at different time periods.

PMID- 22411854
TI  - Recurrent horizontal transfer of bacterial toxin genes to eukaryotes.
AB  - In this work, we report likely recurrent horizontal (lateral) gene transfer
      events of genes encoding pore-forming toxins of the aerolysin family between
      species belonging to different kingdoms of life. Clustering based on pairwise
      similarity and phylogenetic analysis revealed several distinct aerolysin sequence
      groups, each containing proteins from multiple kingdoms of life. These results
      strongly support at least six independent transfer events between distantly
      related phyla in the evolutionary history of one protein family and discount
      selective retention of ancestral genes as a plausible explanation for this patchy
      phylogenetic distribution. We discuss the possible roles of these proteins and
      show evidence for a convergent new function in two extant species. We hypothesize
      that certain gene families are more likely to be maintained following horizontal
      gene transfer from commensal or pathogenic organism to its host if they 1) can
      function alone; and 2) are immediately beneficial for the ecology of the
      organism, as in the case of pore-forming toxins which can be utilized in
      multicellular organisms for defense and predation.

PMID- 22411855
TI  - Detecting selective sweeps from pooled next-generation sequencing samples.
AB  - Due to its cost effectiveness, next-generation sequencing of pools of individuals
      (Pool-Seq) is becoming a popular strategy for characterizing variation in
      population samples. Because Pool-Seq provides genome-wide SNP frequency data, it
      is possible to use them for demographic inference and/or the identification of
      selective sweeps. Here, we introduce a statistical method that is designed to
      detect selective sweeps from pooled data by accounting for statistical challenges
      associated with Pool-Seq, namely sequencing errors and random sampling among
      chromosomes. This allows for an efficient use of the information: all base calls
      are included in the analysis, but the higher credibility of regions with higher
      coverage and base calls with better quality scores is accounted for. Computer
      simulations show that our method efficiently detects sweeps even at very low
      coverage (0.5* per chromosome). Indeed, the power of detecting sweeps is similar
      to what we could expect from sequences of individual chromosomes. Since the
      inference of selective sweeps is based on the allele frequency spectrum (AFS), we
      also provide a method to accurately estimate the AFS provided that the quality
      scores for the sequence reads are reliable. Applying our approach to Pool-Seq
      data from Drosophila melanogaster, we identify several selective sweep signatures
      on chromosome X that include some previously well-characterized sweeps like the
      wapl region.

PMID- 22411857
TI  - Theoretical investigation on SERS of pyridine adsorbed on Cn clusters induced by
      charge transfer: a hint that SERS could be applied on many materials.
AB  - The SERS spectra of pyridine-C(n) (n=1-6) complexes are investigated
      theoretically. The obtained enhancement factors of about 10(2)-10(3) in the pre
      resonance Raman spectrum calculations are attributed to charge-transfer
      transitions from the carbon clusters to pyridine, where a good match of band
      structures between substrates and probe molecules is essential.

PMID- 22411856
TI  - Resolving multiple protein-peptide binding events: implication for HLA-DQ2
      mediated antigen presentation in celiac disease.
AB  - Techniques that can effectively separate protein-peptide complexes from free
      peptides have shown great value in major histocompatibility complex (MHC)-peptide
      binding studies. However, most of the available techniques are limited to
      measuring the binding of a single peptide to an MHC molecule. As antigen
      presentation in vivo involves both endogenous ligands and exogenous antigens, the
      deconvolution of multiple binding events necessitates the implementation of a
      more powerful technique. Here we show that capillary electrophoresis coupled to
      fluorescence detection (CE-FL) can resolve multiple MHC-peptide binding events
      owing to its superior resolution and the ability to simultaneously monitor
      multiple emission channels. We utilized CE-FL to investigate competition and
      displacement of endogenous peptides by an immunogenic gluten peptide for binding
      to HLA-DQ2. Remarkably, this immunogenic peptide could displace CLIP peptides
      from the DQ2 binding site at neutral but not acidic pH. This unusual ability of
      the gluten peptide supports a direct loading mechanism of antigen presentation in
      extracellular environment, a property that could explain the antigenicity of
      dietary gluten in celiac disease.

PMID- 22411858
TI  - De Barsy Syndrome: a genetically heterogeneous autosomal recessive cutis laxa
      syndrome related to P5CS and PYCR1 dysfunction.

PMID- 22411859
TI  - Generation of mineral density distribution maps from subject-specific models of
      mandibles - a preliminary study.
AB  - BACKGROUND: Determination of the mineral content of bone and its distribution by
      computed tomography (CT) enables one to define the insertion points for
      prosthetic devices, or determine the degree of healing in cases of fracture or
      surgical intervention. The use of subject-specific models allows mapping of the
      spatial structure and the mineral content of the bone graphically and
      quantitatively. METHODS: Subject-specific models and mineral density maps from
      pig jaws were developed using segmentation, transcription tools and finite
      element analysis software. This study considered six frozen heads from pigs aged
      10-12 months, and phantom solutions of K(2) HPO(4) . The predicted bone mass of
      each jaw was compared with its respective ash mass after incineration. RESULTS:
      The tridimensional maps show highest density values at the molar cusp and within
      the symphysis. The average percentage error relative to the mineral density maps
      was -18.4%. The radiation dose was reduced by a factor of eight from the
      recommended maximum without compromising the precision of the models.
      CONCLUSIONS: The computed tridimensional mineral density maps illustrate,
      numerically and graphically, the spatial distribution of the density field within
      the mandibular bone. These maps could facilitate the location of insertion points
      or determine the evolution of the mineralization level of a patient's bone
      tissue.

PMID- 22411860
TI  - Benign catalysis with iron: unique selectivity in catalytic isomerization
      reactions of olefins.
AB  - The use of noble metal catalysts in homogeneous catalysis has been well
      established. Due to their price and limited availability, there is growing
      interest in the substitution of such precious metal complexes with readily
      available and bio-relevant catalysts. In particular, iron is a "rising star" in
      catalysis. Herein, we present a general and selective iron-catalyzed
      monoisomerization of olefins, which allows for the selective generation of 2
      olefins. Typically, common metal complexes give mixtures of various internal
      olefins. Both bulk-scale terminal olefins and functionalized terminal olefins
      give the corresponding products under mild conditions in good to excellent
      yields. The proposed reaction mechanism was elucidated by in situ NMR studies and
      supported by DFT calculations and extended X-ray absorption fine structure
      (EXAFS) measurements.

PMID- 22411861
TI  - Immunization and Bell's palsy in children: a case-centered analysis.
AB  - Bell's palsy (BP) is an acute and idiopathic paralysis of the facial nerve, with
      an estimated incidence ranging from 11.5 per 100,000 person-years to 53.3 per
      100,000 person-years in different populations. BP has been reported following
      immunization with inactivated trivalent influenza vaccine (TIV) and hepatitis B
      virus (HBV) vaccine. Epidemiologic studies examining this association among
      children are lacking. From 2001 through 2006, all children aged <=18 years
      diagnosed with BP within the Kaiser Permanente Northern California population
      were identified using International Classification of Diseases, Ninth Revision,
      code 351.0. All electronically identified cases were reviewed and adjudicated by
      an otolaryngologist (n = 233). Using a case-centered approach, the authors
      examined the risk of BP during 3 risk intervals. Immunization with TIV (odds
      ratio (OR) = 0.7, 95% confidence interval (CI): 0.2, 2.8), HBV vaccine (OR = 0.8,
      95% CI: 0.2, 2.4), or any vaccine (treating all vaccines combined; OR = 0.9, 95%
      CI: 0.6, 1.4) was not associated with increased risk of BP 1-28 days after
      immunization. Similarly, no association was found between vaccines and BP during
      the periods 1-14 and 29-56 days following immunization. Results of this study
      suggest that there is no association between immunization and BP in children.

PMID- 22411862
TI  - The epidemiology of interpandemic and pandemic influenza in Vietnam, 2007-2010:
      the Ha Nam household cohort study I.
AB  - Prospective community-based studies have provided fundamental insights into the
      epidemiology of influenza in temperate regions, but few comparable studies have
      been undertaken in the tropics. The authors conducted prospective influenza
      surveillance and intermittent seroprevalence surveys in a household-based cohort
      in Vietnam between December 2007 and April 2010, resulting in 1,793 person
      seasons of influenza surveillance. Age- and sex-standardized estimates of the
      risk of acquiring any influenza infection per season in persons 5 years of age or
      older were 21.1% (95% confidence interval: 17.4, 24.7) in season 1, 26.4% (95%
      confidence interval: 22.6, 30.2) in season 2, and 17.0% (95% confidence interval:
      13.6, 20.4) in season 3. Some individuals experienced multiple episodes of
      infection with different influenza types/subtypes in the same season (n = 27) or
      reinfection with the same subtype in different seasons (n = 22). The highest risk
      of influenza infection was in persons 5-9 years old, in whom the risk of
      influenza infection per season was 41.8%. Although the highest infection risk was
      in school-aged children, there were important heterogeneities in the age of
      infection by subtype and season. These heterogeneities could influence the impact
      of school closure and childhood vaccination on influenza transmission in tropical
      areas, such as Vietnam.

PMID- 22411864
TI  - Epidemiology, austerity, and innovation.
AB  - In considering the state of epidemiologic research, these are the "best" and the
      "worst" of times-the "best" from the perspective of scientific opportunities and
      the "worst" from the perspective of funding. In this commentary, the authors
      address this time of funding austerity from the points of view of individual
      researchers and research institutions. For researchers, the new tools of "
      omics," large databases, communication by means of the World Wide Web, and global
      access offer ever-expanding scientific opportunities. The authors comment on
      research directions for which there is an enhanced likelihood of funding success:
      clinical and translational research, outcomes and effectiveness research, and
      global health research. The authors emphasize the need to be innovative and not
      bound by the conventional. For institutions, the authors suggest attention to
      innovation and impact, social networking, and finding the "right size" for
      training programs. Academic institutions also need to invest, supporting
      researchers and their ideas. Epidemiologists need to be true to their mission and
      prove that they can use innovation to advance health and welfare in a measurable
      way. Doing so will ensure that over the long term, epidemiologic research will
      remain a cornerstone for advancing population health.

PMID- 22411865
TI  - New models for large prospective studies: is there a better way?
AB  - Large prospective cohort studies are critical for identifying etiologic factors
      for disease, but they require substantial long-term research investment. Such
      studies can be conducted as multisite consortia of academic medical centers,
      combinations of smaller ongoing studies, or a single large site such as a
      dominant regional health-care provider. Still another strategy relies upon
      centralized conduct of most or all aspects, recruiting through multiple temporary
      assessment centers. This is the approach used by a large-scale national resource
      in the United Kingdom known as the "UK Biobank," which completed
      recruitment/examination of 503,000 participants between 2007 and 2010 within
      budget and ahead of schedule. A key lesson from UK Biobank and similar studies is
      that large studies are not simply small studies made large but, rather, require
      fundamentally different approaches in which "process" expertise is as important
      as scientific rigor. Embedding recruitment in a structure that facilitates
      outcome determination, utilizing comprehensive and flexible information
      technology, automating biospecimen processing, ensuring broad consent, and
      establishing essentially autonomous leadership with appropriate oversight are all
      critical to success. Whether and how these approaches may be transportable to the
      United States remain to be explored, but their success in studies such as UK
      Biobank makes a compelling case for such explorations to begin.

PMID- 22411866
TI  - Invited commentary: Immunization and Bell's palsy in children.
AB  - Based on case reports, it has been speculated that certain vaccines may increase
      the risk of Bell's palsy. In a study using a novel approach (case-centered
      analysis) among children aged 18 years or less, results of which appear in this
      issue of the Journal, Rowhani-Rahbar et al. (Am J Epidemiol. 2012;175(9):878-885)
      found no association between immunization with trivalent influenza vaccine (TIV),
      hepatitis B virus (HBV) vaccine, or any vaccine (all vaccines combined) and
      Bell's palsy (definite and probable cases combined). In this commentary, the
      author evaluates the validity of the case-centered approach. In the study by
      Rowhani-Rahbar et al., the study population was not representative of the
      population of children at risk. The analytical approach resulted in the loss of
      information for 72% of the cases. There were insufficient data to assess TIV and
      HBV. Only the risk for all vaccines could be assessed, and only if it was assumed
      that the findings could be generalized. Possible effect modification by
      antecedent vaccination could not be assessed. The author concludes that a nested
      case-control study would have been more statistically robust and more
      informative.

PMID- 22411868
TI  - SRC is a signaling mediator in FLT3-ITD- but not in FLT3-TKD-positive AML.
AB  - Mutations of Fms-like tyrosine kinase 3 (FLT3) are among the most frequently
      detected molecular abnormalities in AML patients. Internal tandem duplications
      (ITDs) are found in approximately 25% and point mutations within the second
      tyrosine kinase domain (TKD) in approximately 7% of AML patients. Patients
      carrying the FLT3-ITD but not the FLT3-TKD mutation have a significantly worse
      prognosis. Therefore, both FLT3 mutations seem to exert different biologic
      functions. FLT3-ITD but not FLT3-TKD has been shown to induce robust activation
      of the STAT5 signaling pathway. In the present study, we investigated the
      mechanisms leading to differential STAT5 activation and show that FLT3-ITD but
      not FLT3-TKD uses SRC to activate STAT5. Coimmunoprecipitation and pull-down
      experiments revealed an exclusive interaction between SRC but not other Src
      family kinases and FLT3-ITD, which is mediated by the SRC SH2 domain. We
      identified tyrosines 589 and 591 of FLT3-ITD to be essential for SRC binding and
      subsequent STAT5 activation. Using site-specific Abs, we found that both residues
      were significantly more strongly phosphorylated in FLT3-ITD compared with FLT3
      TKD. SRC inhibition and knock-down blocked STAT5 activation and proliferation
      induced by FLT3-ITD but not by FLT3-TKD. We conclude that SRC might be a
      therapeutic target in FLT3-ITD(+) AML.

PMID- 22411867
TI  - Dasatinib inhibits proinflammatory functions of mature human neutrophils.
AB  - Dasatinib is a tyrosine kinase inhibitor used to treat imatinib-resistant chronic
      myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic
      leukemia. At present, little is known about how dasatinib influences nonmalignant
      cells. In the present study, we tested the effect of dasatinib on functional
      responses of normal mature human neutrophils. Dasatinib completely blocked
      integrin- and Fc-receptor-mediated neutrophil functions, with the lowest IC(50)
      values below 10nM under serum-free conditions. Dasatinib caused a partial
      inhibition of neutrophil responses triggered by G-protein-coupled receptors and
      had a moderate effect on neutrophil responses triggered by microbial compounds.
      Whereas dasatinib inhibited neutrophil chemotaxis under static conditions in 2
      dimensions, it did not affect migration under flow conditions or in 3-dimensional
      environments. Dasatinib did not have any major effect on phagocytosis or killing
      of bacteria by neutrophils. Adhesion of human neutrophils in the presence of
      whole serum was significantly inhibited by 50-100nM dasatinib, which corresponds
      to the reported serum concentrations in dasatinib-treated patients. Finally, ex
      vivo adhesion of mouse peripheral blood neutrophils was strongly reduced after
      oral administration of 5 mg/kg of dasatinib. Those results suggest that dasatinib
      treatment may affect the proinflammatory functions of mature neutrophils and
      raise the possibility that dasatinib-related compounds may provide clinical
      benefit in neutrophil-mediated inflammatory diseases.

PMID- 22411869
TI  - Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B
      cell development and function.
AB  - The Wiskott-Aldrich syndrome protein (WASP) is a key cytoskeletal regulator of
      hematopoietic cells. Although WASP-knockout (WKO) mice have aberrant B-cell
      cytoskeletal responses, B-cell development is relatively normal. We hypothesized
      that N-WASP, a ubiquitously expressed homolog of WASP, may serve some redundant
      functions with WASP in B cells. In the present study, we generated mice lacking
      WASP and N-WASP in B cells (conditional double knockout [cDKO] B cells) and show
      that cDKO mice had decreased numbers of follicular and marginal zone B cells in
      the spleen. Receptor-induced activation of cDKO B cells led to normal
      proliferation but a marked reduction of spreading compared with wild-type and WKO
      B cells. Whereas WKO B cells showed decreased migration in vitro and homing in
      vivo compared with wild-type cells, cDKO B cells showed an even more pronounced
      decrease in the migratory response in vivo. After injection of 2,4,6
      trinitrophenol (TNP)-Ficoll, cDKO B cells had reduced antigen uptake in the
      splenic marginal zone. Despite high basal serum IgM, cDKO mice mounted a reduced
      immune response to the T cell-independent antigen TNP-Ficoll and to the T cell
      dependent antigen TNP-keyhole limpet hemocyanin. Our results reveal that the
      combined activity of WASP and N-WASP is required for peripheral B-cell
      development and function.

PMID- 22411870
TI  - Polycomb group ring finger 1 cooperates with Runx1 in regulating differentiation
      and self-renewal of hematopoietic cells.
AB  - The transcription factor runt-related transcription factor 1 (Runx1) is essential
      for the establishment of definitive hematopoiesis during embryonic development.
      In adult blood homeostasis, Runx1 plays a pivotal role in the maturation of
      lymphocytes and megakaryocytes. Furthermore, Runx1 is required for the regulation
      of hematopoietic stem and progenitor cells. However, how Runx1 orchestrates self
      renewal and lineage choices in combination with other factors is not well
      understood. In the present study, we describe a genome-scale RNA interference
      screen to detect genes that cooperate with Runx1 in regulating hematopoietic stem
      and progenitor cells. We identify the polycomb group protein Pcgf1 as an
      epigenetic regulator involved in hematopoietic cell differentiation and show that
      simultaneous depletion of Runx1 and Pcgf1 allows sustained self-renewal while
      blocking differentiation of lineage marker-negative cells in vitro. We found an
      up-regulation of HoxA cluster genes on Pcgf1 knock-down that possibly accounts
      for the increase in self-renewal. Moreover, our data suggest that cells lacking
      both Runx1 and Pcgf1 are blocked at an early progenitor stage, indicating that a
      concerted action of the transcription factor Runx1, together with the epigenetic
      repressor Pcgf1, is necessary for terminal differentiation. The results of the
      present study uncover a link between transcriptional and epigenetic regulation
      that is required for hematopoietic differentiation.

PMID- 22411872
TI  - How we choose factor VIII to treat hemophilia.
AB  - In high-income countries, the large availability of coagulation factors for
      replacement therapy of patients with hemophilia A has raised the life expectancy
      of these lifelong bleeders to that of males from the general population. The
      practicing clinician is offered a multitude of choices among several commercial
      brands of factor VIII extracted from human plasma or engineered from mammalian
      cell cultures by means of recombinant DNA technology. This article has the goal
      to offer our opinions on how to choose among the different products, that we
      consider interchangeable relevant to their clinical efficacy in the control of
      bleeding and safety from pathogen transmission. Hence, the main determinants of
      our choices are price and the risk of occurrence of factor VIII inhibitory
      alloantibodies. With this as background, we present the rationale underlying the
      choices for different categories of patients with severe hemophilia A: previously
      untreated patients, multiply treated patients, and patients undergoing immune
      tolerance induction with large doses of factor VIII to eradicate inhibitors.
      Mention is also made to the possible strategies that should be implemented to
      make available coagulation factors for replacement therapy in developing
      countries.

PMID- 22411871
TI  - Rac2-MRC-cIII-generated ROS cause genomic instability in chronic myeloid leukemia
      stem cells and primitive progenitors.
AB  - Chronic myeloid leukemia in chronic phase (CML-CP) is induced by BCR-ABL1
      oncogenic tyrosine kinase. Tyrosine kinase inhibitors eliminate the bulk of CML
      CP cells, but fail to eradicate leukemia stem cells (LSCs) and leukemia
      progenitor cells (LPCs) displaying innate and acquired resistance, respectively.
      These cells may accumulate genomic instability, leading to disease relapse and/or
      malignant progression to a fatal blast phase. In the present study, we show that
      Rac2 GTPase alters mitochondrial membrane potential and electron flow through the
      mitochondrial respiratory chain complex III (MRC-cIII), thereby generating high
      levels of reactive oxygen species (ROS) in CML-CP LSCs and primitive LPCs. MRC
      cIII-generated ROS promote oxidative DNA damage to trigger genomic instability,
      resulting in an accumulation of chromosomal aberrations and tyrosine kinase
      inhibitor-resistant BCR-ABL1 mutants. JAK2(V617F) and FLT3(ITD)-positive
      polycythemia vera cells and acute myeloid leukemia cells also produce ROS via MRC
      cIII. In the present study, inhibition of Rac2 by genetic deletion or a small
      molecule inhibitor and down-regulation of mitochondrial ROS by disruption of MRC
      cIII, expression of mitochondria-targeted catalase, or addition of ROS-scavenging
      mitochondria-targeted peptide aptamer reduced genomic instability. We postulate
      that the Rac2-MRC-cIII pathway triggers ROS-mediated genomic instability in LSCs
      and primitive LPCs, which could be targeted to prevent the relapse and malignant
      progression of CML.

PMID- 22411874
TI  - Successful treatment with doripenem of ventriculitis due to Achromobacter
      xylosoxidans.

PMID- 22411873
TI  - Vascular endothelial hyperpermeability induces the clinical symptoms of Clarkson
      disease (the systemic capillary leak syndrome).
AB  - The systemic capillary leak syndrome (SCLS) is a rare disorder characterized by
      transient episodes of hypotensive shock and anasarca thought to arise from
      reversible microvascular barrier dysfunction. Although the high prevalence of a
      monoclonal gammopathy of unknown significance in SCLS suggests a pathogenic
      contribution of endogenous immunoglobulins, the mechanisms of vascular
      hyperpermeability remain obscure. Herein, we report clinical and molecular
      findings on 23 patients, the largest SCLS case series to date. Application of
      episodic SCLS sera, but neither the purified immunoglobulin fraction nor sera
      obtained from patients during remission, to human microvascular endothelial cells
      caused vascular endothelial cadherin internalization, disruption of
      interendothelial junctions, actin stress fiber formation, and increased
      permeability in complementary functional assays without inducing endothelial
      apoptosis. Intravenous immunoglobulin, one promising therapy for SCLS, mitigated
      the permeability effects of episodic sera. Consistent with the presence of
      endogenous, nonimmunoglobulin, circulating permeability factor(s) constrained to
      SCLS episodes, we found that vascular endothelial growth factor (VEGF) and
      angiopoietin 2 (Ang2), were elevated in episodic SCLS sera but not in remission
      sera. Ab-based inhibition of Ang2 counteracted permeability induced by episodic
      SCLS sera. Comparable experiments with anti-VEGF Ab (bevacizumab) yielded less
      interpretable results, probably because of endothelial toxicity of VEGF
      withdrawal. Our results support a model of SCLS pathogenesis in which
      nonimmunoglobulin humoral factors such as VEGF and Ang2 contribute to transient
      endothelial contraction, suggesting a molecular mechanism for this highly lethal
      disorder.

PMID- 22411875
TI  - A constricting differential--a case of severe anaemia, weight loss and
      pericarditis due to Tropheryma whipplei infection.

PMID- 22411876
TI  - Bilateral flank pain and epigastralgia in a young man with pulmonary
      tuberculosis.

PMID- 22411878
TI  - Audiological findings in Williams syndrome: a study of 69 patients.
AB  - The aim of this study was to investigate, in a clinical setting, the auditory
      function of a group of individuals affected by Williams syndrome (WS). Sixty-nine
      patients with WS, aged 2-30, underwent comprehensive audiological testing
      including air/bone conduction behavioral audiometry, speech audiometry,
      tympanometry and measurement of the acoustic reflex, transient evoked otoacoustic
      emissions and brainstem auditory evoked responses. Hearing loss, defined by a
      pure-tone average above 15 dB HL, affected 22.6% of the patients studied with
      traditional audiometry and was mostly slight in severity. Hearing loss was
      conductive in 9.4% of patients, mainly children with otitis media with effusion,
      and sensorineural in 13.2% of patients. However, 30% of the ears studied had a
      hearing impairment in the high frequency range (high-frequency pure-tone
      audiometry above 15 dB HL), higher in participants above 15 years (46.15%) than
      in the younger ones (23.45%). Contralateral stapedial reflexes were present in
      all patients with A-type tympanograms. Transient otoacoustic emissions were
      absent in 44% of the ears of patients with normal hearing. Brainstem auditory
      evoked responses fell within normal ranges thus confirming the absence of
      retrocochlear dysfunction. Although hearing loss does not seem to be frequent, a
      cochlear fragility, especially in the high frequency range, related to outer hair
      cells is characteristic of WS. Therefore we strongly recommend monitoring
      patients affected by WS using annual audiometric tests and performing otoacoustic
      emissions in order to identify a subclinical cochlear dysfunction which might
      benefit from an audiological follow up before the possible onset of hearing loss.

PMID- 22411879
TI  - Global Immunization Vision and Strategy (GIVS): a mid-term analysis of progress
      in 50 countries.
AB  - Within the overall framework set out in the Global Immunization Vision and
      Strategy (GIVS) for the period 2006-2015, over 70 countries had developed
      comprehensive Multi-Year Plans (cMYPs) by 2008, outlining their plans for
      implementing the GIVS strategies and for attaining the GIVS Goals at the midpoint
      in 2010 or earlier. These goals are to: (1) reach >=90% and >=80% vaccination
      coverage at national and district level, respectively; and (2) reduce measles
      related mortality by 90% compared with the 2000 level. Fifty cMYPs were analysed
      along the four strategic areas of the GIVS: (1) protecting more people in a
      changing world; (2) introducing new vaccines and technologies; (3) integrating
      immunization, other health interventions and surveillance in the health system
      context; and (4) immunizing in the context of global interdependence. By 2010,
      all 50 countries planned to have introduced hepatitis B (HepB) vaccine, 48 the
      Haemophilus influenzae type B (Hib) vaccine and only a few countries had firm
      plans to introduce pneumococcal or rotavirus vaccines. Countries seem to be
      inadequately prepared in terms of cold-chain requirements to deal with the
      expected increases in storage that will be required for vaccines, and in making
      provisions to establish a corresponding surveillance system for planned new
      vaccine introductions. Immunization contacts are used to deliver other health
      interventions, especially in the countries in the World Health Organization (WHO)
      Africa Region. The cost for the planned immunization activities will double to
      U$27 per infant, of which U$5 per infant is the expected shortfall. Global
      Alliance for Vaccines and Immunization (GAVI) funding is becoming the largest
      contributor to immunization programmes.

PMID- 22411880
TI  - National and sub-national analysis of the health benefits and cost-effectiveness
      of strategies to reduce maternal mortality in Afghanistan.
AB  - BACKGROUND: Afghanistan has one of the highest rates of maternal mortality in the
      world. We assess the health outcomes and cost-effectiveness of strategies to
      improve the safety of pregnancy and childbirth in Afghanistan. METHODS: Using
      national and sub-national data, we adapted a previously validated model that
      simulates the natural history of pregnancy and pregnancy-related complications.
      We incorporated data on antenatal care, family planning, skilled birth attendance
      and information about access to transport, referral facilities and quality of
      care. We evaluated single interventions (e.g. family planning) and strategies
      that combined several interventions packaged as integrated services (transport,
      intrapartum care). Outcomes included pregnancy-related complications, maternal
      deaths, maternal mortality ratios, costs and cost-effectiveness ratios. FINDINGS:
      Model-projected reduction in maternal deaths between 1999-2002 and 2007-08
      approximated 20%. Increasing family planning was the most effective individual
      intervention to further reduce maternal mortality; up to 1 in 3 pregnancy-related
      deaths could be prevented if contraception use approached 60%. Nevertheless,
      reductions in maternal mortality reached a threshold (~30% to 40%) without
      strategies that assured women access to emergency obstetrical care. A stepwise
      approach that coupled improved family planning with incremental improvements in
      skilled attendance, transport, referral and appropriate intrapartum care and high
      quality facilities prevented 3 of 4 maternal deaths. Such an approach would cost
      less than US$200 per year of life saved at the national level, well below
      Afghanistan's per capita gross domestic product (GDP), a common benchmark for
      cost-effectiveness. Similar results were noted sub-nationally. INTERPRETATION:
      Our findings reinforce the importance of early intensive efforts to increase
      family planning for spacing and limiting births and to provide control of
      fertility choices. While significant improvements in health delivery
      infrastructure will be required to meet Millennium Development Goal 5, a paced
      systematic effort that invests in scaling up capacity for integrated maternal
      health services as the total fertility rate declines appears feasible and cost
      effective.

PMID- 22411881
TI  - Comparative costs and cost-effectiveness of behavioural interventions as part of
      HIV prevention strategies.
AB  - BACKGROUND: Behavioural interventions have been widely integrated in HIV/AIDS
      social marketing prevention strategies and are considered valuable in settings
      with high levels of risk behaviours and low levels of HIV/AIDS awareness. Despite
      their widespread application, there is a lack of economic evaluations comparing
      different behaviour change communication methods. This paper analyses the costs
      to increase awareness and the cost-effectiveness to influence behaviour change
      for five interventions in Benin. METHODS: Cost and cost-effectiveness analyses
      used economic costs and primary effectiveness data drawn from surveys. Costs were
      collected for provider inputs required to implement the interventions in 2009 and
      analysed by 'person reached'. Cost-effectiveness was analysed by 'person
      reporting systematic condom use'. Sensitivity analyses were performed on all
      uncertain variables and major assumptions. RESULTS: Cost-per-person reached
      varies by method, with public outreach events the least costly (US$2.29) and
      billboards the most costly (US$25.07). Influence on reported behaviour was
      limited: only three of the five interventions were found to have a significant
      statistical correlation with reported condom use (i.e. magazines, radio
      broadcasts, public outreach events). Cost-effectiveness ratios per person
      reporting systematic condom use resulted in the following ranking: magazines,
      radio and public outreach events. Sensitivity analyses indicate rankings are
      insensitive to variation of key parameters although ratios must be interpreted
      with caution. CONCLUSION: This analysis suggests that while individual
      interventions are an attractive use of resources to raise awareness, this may not
      translate into a cost-effective impact on behaviour change. The study found that
      the extensive reach of public outreach events did not seem to influence behaviour
      change as cost-effectively when compared with magazines or radio broadcasts.
      Behavioural interventions are context-specific and their effectiveness influenced
      by a multitude of factors. Further analyses using a quasi-experimental design
      would be useful to programme implementers and policy makers as they face
      decisions regarding which HIV prevention activities to prioritize.

PMID- 22411882
TI  - The role of social networks in the governance of health systems: the case of eye
      care systems in Ghana.
AB  - Efforts have been increasingly invested to improve local health systems'
      capacities in developing countries. We describe the application of innovative
      methods based on a social network analysis approach. The findings presented refer
      to a study carried out between July 2008 and January 2010 in the Brong Ahafo
      region of Ghana. Social network analysis methods were applied in five different
      districts using the software package Ucinet to calculate the various properties
      of the social network of eye care providers. The study focused on the managerial
      decisions made by Ghanaian district hospital managers about the governance of the
      health system. The study showed that the health system in the Brong Ahafo region
      experienced significant changes specifically after a key shock, the departure of
      an international organization. Several other actors at different levels of the
      network disappeared, the positions of nurses and hospital managers changed,
      creating new relationships and power balances that resulted in a change in the
      general structure of the network. The system shifted from a centralized and dense
      hierarchical network towards an enclaved network composed of five sub-networks.
      The new structure was less able to respond to shocks, circulate information and
      knowledge across scales and implement multi-scale solutions than that which it
      replaced. Although the network became less resilient, it responded better to the
      management needs of the hospital managers who now had better access to
      information, even if this information was partial. The change of the network over
      time also showed the influence of the international organization on generating
      links and creating connections between actors from different levels. The findings
      of the study reveal the importance of creating international health connections
      between actors working in different spatial scales of the health system.

PMID- 22411884
TI  - A one-pot method for the selective conversion of hemicellulose from crop waste
      into C5 sugars and furfural by using solid acid catalysts.
AB  - We present a solid-acid catalyzed one-pot method for the selective conversion of
      solid hemicellulose without its separation from other lignocellulosic components,
      such as cellulose and lignin. The reactions were carried out in aqueous and
      biphasic media to yield xylose, arabinose, and furfural. To overcome the
      drawbacks posed by mineral acid methods in converting hemicelllulose, we used
      heterogeneous catalysts that work at neutral pH. In a batch reactor, these
      heterogeneous catalysts, such as solid acids (zeolites, clays, metal oxides
      etc.), resulted in >90 % conversion of hemicellulose. It has been shown that the
      selectivity for the products can be tuned by changing the reaction conditions,
      for example, a reaction carried out in water at 170  degrees C for 1 h with HBeta
      (Si/Al=19) and HUSY (Si/Al=15) catalysts gave yields of 62 and 56 % for xylose
      and arabinose, respectively. With increased reaction time (6 h) and in presence
      of only water, HUSY resulted in yields of 30 % xylose + arabinose and 18 %
      furfural. However, in a biphasic reaction system (water + p-xylene, 170  degrees
      C, 6 h) yields of 56 % furfural with 17 % xylose+arabinose could be achieved. It
      was shown that with the addition of organic solvent the furfural yield could be
      increased from 18 to 56 %. Under optimized reaction conditions, >90 % carbon
      balance was observed. The study revealed that catalysts were recyclable with a 20
      % drop in activity for each subsequent run. It was observed that temperature,
      pressure, reaction time, substrate to catalyst ratio, solvent, and so forth had
      an effect on product formation. The catalysts were characterized by means of X
      ray diffraction, temperature-programmed desorption of NH(3), inductively coupled
      plasma spectroscopy, elemental analysis, and solid-state NMR ((29)Si, (27)Al)
      spectroscopy techniques.

PMID- 22411885
TI  - A multigrid fluid pressure solver handling separating solid boundary conditions.
AB  - We present a multigrid method for solving the linear complementarity problem
      (LCP) resulting from discretizing the Poisson equation subject to separating
      solid boundary conditions in an Eulerian liquid simulation's pressure projection
      step. The method requires only a few small changes to a multigrid solver for
      linear systems. Our generalized solver is fast enough to handle 3D liquid
      simulations with separating boundary conditions in practical domain sizes.
      Previous methods could only handle relatively small 2D domains in reasonable
      time, because they used expensive quadratic programming (QP) solvers. We
      demonstrate our technique in several practical scenarios, including nonaxis
      aligned containers and moving solids in which the omission of separating boundary
      conditions results in disturbing artifacts of liquid sticking to solids. Our
      measurements show, that the convergence rate of our LCP solver is close to that
      of a standard multigrid solver.

PMID- 22411886
TI  - Scalable Multivariate Volume Visualization and Analysis Based on Dimension
      Projection and Parallel Coordinates.
AB  - In this paper, we present an effective and scalable system for multivariate
      volume data visualization and analysis with a novel transfer function interface
      design that tightly couples parallel coordinates plots (PCP) and MDS-based
      dimension projection plots. In our system, the PCP visualizes the data
      distribution of each variate (dimension) and the MDS plots project features. They
      are integrated seamlessly to provide flexible feature classification without
      context switching between different data presentations during the user
      interaction. The proposed interface enables users to identify relevant
      correlation clusters and assign optical properties with lassos, magic wand, and
      other tools. Furthermore, direct sketching on the volume rendered images has been
      implemented to probe and edit features. With our system, users can interactively
      analyze multivariate volumetric data sets by navigating and exploring feature
      spaces in unified PCP and MDS plots. To further support large-scale multivariate
      volume data visualization and analysis, Scalable Pivot MDS (SPMDS), parallel
      adaptive continuous PCP rendering, as well as parallel rendering techniques are
      developed and integrated into our visualization system. Our experiments show that
      the system is effective in multivariate volume data visualization and its
      performance is highly scalable for data sets with different sizes and number of
      variates. 

PMID- 22411887
TI  - Detail-preserving controllable deformation from sparse examples.
AB  - Recent advances in laser scanning technology have made it possible to faithfully
      scan a real object with tiny geometric details, such as pores and wrinkles.
      However, a faithful digital model should not only capture static details of the
      real counterpart but also be able to reproduce the deformed versions of such
      details. In this paper, we develop a data-driven model that has two components;
      the first accommodates smooth large-scale deformations and the second captures
      high-resolution details. Large-scale deformations are based on a nonlinear
      mapping between sparse control points and bone transformations. A global mapping,
      however, would fail to synthesize realistic geometries from sparse examples, for
      highly deformable models with a large range of motion. The key is to train a
      collection of mappings defined over regions locally in both the geometry and the
      pose space. Deformable fine-scale details are generated from a second nonlinear
      mapping between the control points and per-vertex displacements. We apply our
      modeling scheme to scanned human hand models, scanned face models, face models
      reconstructed from multiview video sequences, and manually constructed dinosaur
      models. Experiments show that our deformation models, learned from extremely
      sparse training data, are effective and robust in synthesizing highly deformable
      models with rich fine features, for keyframe animation as well as performance
      driven animation. We also compare our results with those obtained by alternative
      techniques.

PMID- 22411888
TI  - Animating Wrinkles by Example on Non-Skinned Cloth.
AB  - The simulation of cloth with rich folds and wrinkles is a computationally
      expensive process. In this paper, we introduce an example-based algorithm for
      fast animation of plausible cloth wrinkles. Our algorithm does not depend on a
      character's pose, therefore it is valid for loose dresses, curtains, etc., not
      just cloth defined by skinning techniques. Central to our approach is a
      correspondence between low and high-resolution cloth deformations, both at the
      training and synthesis stages. Based on this correspondence, we define an
      algorithm for synthesizing cloth wrinkles as a function of the deformation of a
      low-resolution cloth and a set of example poses. We demonstrate the animation of
      plausible high-resolution wrinkles at high frame rates, suitable for interactive
      applications such as video games. 

PMID- 22411889
TI  - Evaluating the Role of Time in Investigative Analysis of Document Collections.
AB  - Time is a universal and essential aspect of data in any investigative analysis.
      It helps analysts establish causality, build storylines from evidence, and reject
      infeasible hypotheses. For this reason, many investigative analysis tools provide
      visual representations designed for making sense of temporal data. However, the
      field of visual analytics still needs more evidence explaining how temporal
      visualization actually aids the analysis process, as well as design
      recommendations for how to build these visualizations. To fill this gap, we
      conducted an insight-based qualitative study to investigate the influence of
      temporal visualization on investigative analysis. We found that visualizing
      temporal information helped participants externalize chains of events. Another
      contribution of our work is the lightweight evaluation approach used to collect,
      visualize, and analyze insight. 

PMID- 22411890
TI  - Preserving fluid sheets with adaptively sampled anisotropic particles.
AB  - This paper presents a particle-based model for preserving fluid sheets of
      animated liquids with an adaptively sampled Fluid-Implicit-Particle (FLIP)
      method. In our method, we preserve fluid sheets by filling the breaking sheets
      with particle splitting in the thin regions, and by collapsing them in the deep
      water. To identify the critically thin parts, we compute the anisotropy of the
      particle neighborhoods, and use this information as a resampling criterion to
      reconstruct thin liquid surfaces. Unlike previous approaches, our method does not
      suffer from diffusive surfaces or complex remeshing operations, and robustly
      handles topology changes with the use of a meshless representation. We extend the
      underlying FLIP model with an anisotropic position correction to improve the
      particle spacing, and adaptive sampling to efficiently perform simulations of
      larger volumes. Due to the Lagrangian nature of our method, it can be easily
      implemented and efficiently parallelized. The results show that our method can
      produce visually complex liquid animations with thin structures and vivid
      motions.

PMID- 22411891
TI  - Transient dynamics of reduced-order models of genetic regulatory networks.
AB  - In systems biology, a number of detailed genetic regulatory networks models have
      been proposed that are capable of modeling the fine-scale dynamics of gene
      expression. However, limitations on the type and sampling frequency of
      experimental data often prevent the parameter estimation of the detailed models.
      Furthermore, the high computational complexity involved in the simulation of a
      detailed model restricts its use. In such a scenario, reduced-order models
      capturing the coarse-scale behavior of the network are frequently applied. In
      this paper, we analyze the dynamics of a reduced-order Markov Chain model
      approximating a detailed Stochastic Master Equation model. Utilizing a reduction
      mapping that maintains the aggregated steady-state probability distribution of
      stochastic master equation models, we provide bounds on the deviation of the
      Markov Chain transient distribution from the transient aggregated distributions
      of the stochastic master equation model.

PMID- 22411892
TI  - A comparative assessment of ranking accuracies of conventional and machine
      learning-based scoring functions for protein-ligand binding affinity prediction.
AB  - Accurately predicting the binding affinities of large sets of protein-ligand
      complexes efficiently is a key challenge in computational biomolecular science,
      with applications in drug discovery, chemical biology, and structural biology.
      Since a scoring function (SF) is used to score, rank, and identify drug leads,
      the fidelity with which it predicts the affinity of a ligand candidate for a
      protein's binding site has a significant bearing on the accuracy of virtual
      screening. Despite intense efforts in developing conventional SFs, which are
      either force-field based, knowledge-based, or empirical, their limited ranking
      accuracy has been a major roadblock toward cost-effective drug discovery.
      Therefore, in this work, we explore a range of novel SFs employing different
      machine-learning (ML) approaches in conjunction with a variety of physicochemical
      and geometrical features characterizing protein-ligand complexes. We assess the
      ranking accuracies of these new ML-based SFs as well as those of conventional SFs
      in the context of the 2007 and 2010 PDBbind benchmark data sets on both diverse
      and protein-family-specific test sets. We also investigate the influence of the
      size of the training data set and the type and number of features used on ranking
      accuracy. Within clusters of protein-ligand complexes with different ligands
      bound to the same target protein, we find that the best ML-based SF is able to
      rank the ligands correctly based on their experimentally determined binding
      affinities 62.5 percent of the time and identify the top binding ligand 78.1
      percent of the time. For this SF, the Spearman correlation coefficient between
      ranks of ligands ordered by predicted and experimentally determined binding
      affinities is 0.771. Given the challenging nature of the ranking problem and that
      SFs are used to screen millions of ligands, this represents a significant
      improvement over the best conventional SF we studied, for which the corresponding
      ranking performance values are 57.8 percent, 73.4 percent, and 0.677.

PMID- 22411893
TI  - In search for cross-reactivity to immunophenotype equine mesenchymal stromal
      cells by multicolor flow cytometry.
AB  - During recent years, cell-based therapies using mesenchymal stem cells (MSC) are
      reported in equine veterinary medicine with increasing frequency. In most cases,
      the isolation and in vitro differentiation of equine MSC are described, but their
      proper immunophenotypic characterization is rarely performed. The lack of a
      single marker specific for MSC and the limited availability of monoclonal
      antibodies (mAbs) for equine MSC in particular, strongly hamper this research. In
      this study, 30 commercial mAbs were screened with flow cytometry for recognizing
      equine epitopes using the appropriate positive controls to confirm their
      specificity. Cross-reactivity was found and confirmed by confocal microscopy for
      CD45, CD73, CD79alpha, CD90, CD105, MHC-II, a monocyte marker, and two clones
      tested for CD29 and CD44. Unfortunately, none of the evaluated CD34 clones
      recognized the equine epitopes on positive control endothelial cells.
      Subsequently, umbilical cord blood-derived undifferentiated equine MSC of the
      fourth passage of six horses were characterized using multicolor flow cytometry
      based on the selected nine-marker panel of both cell surface antigens and
      intracytoplasmatic proteins. In addition, appropriate positive and negative
      controls were included, and the viable single cell population was analyzed by
      excluding dead cells using 7-aminoactinomycin D. Isolated equine MSC of the
      fourth passage were found to be CD29, CD44, CD90 positive and CD45, CD79alpha,
      MHC-II, and a monocyte marker negative. A variable expression was found for CD73
      and CD105. Successful differentiation towards the osteogenic, chondrogenic, and
      adipogenic lineage was used as additional validation. We suggest that this
      selected nine-marker panel can be used for the adequate immunophenotyping of
      equine MSC.

PMID- 22411894
TI  - Overexpression of the sterol 14alpha-demethylase gene (MgCYP51) in Mycosphaerella
      graminicola isolates confers a novel azole fungicide sensitivity phenotype.
AB  - BACKGROUND: The recent evolution towards resistance to azole fungicides in
      European populations of the wheat pathogen Mycosphaerella graminicola has been
      caused by the progressive accumulation of mutations in MgCYP51 gene, encoding the
      azole target sterol 14alpha-demethylase. Particular combinations of mutations
      have been shown specifically to affect the interaction of the MgCYP51 protein
      with different members of the azole class. Although additional mechanisms,
      including increased MgCYP51 expression and enhanced active efflux, have been
      proposed, the genetic changes underlying these mechanisms are unknown. RESULTS:
      Analysis of the azole sensitivities of recent M. graminicola isolates identified
      a novel phenotype, seemingly independent of changes in MgCYP51 coding sequence.
      Characterised by a 7-16-fold reduction in in vitro sensitivity to all azoles
      tested and by growth on seedlings at higher doses of azoles in glasshouse tests
      compared with isolates carrying the same MgCYP51 variant (L50S, S188N, I381V,
      DeltaY459/G460, N513K), isolates with this phenotype constitutively overexpress
      MgCYP51 by between 10- and 40-fold compared with the wild type. Analysis of
      sequences upstream of the predicted MgCYP51 translation start codon identified a
      novel 120 bp indel, considered to be an insertion, in isolates overexpressing
      MgCYP51. CONCLUSIONS: The identification of an insertion in the predicted MgCYP51
      promoter in azole-resistant isolates overexpressing MgCYP51 is the first report
      of a genetic mechanism, other than changes in target-site coding sequence,
      affecting sensitivity to multiple azoles in field isolates of M. graminicola. The
      identification of recent isolates overexpressing MgCYP51 confirms the ongoing
      evolution and diversification of resistance mechanisms in European populations of
      M. graminicola.

PMID- 22411895
TI  - Reduction of CO2 to CO at low overpotential in neutral aqueous solution by a
      Ni(cyclam) complex attached to poly(allylamine).
AB  - Less is more: Nickel cyclam complexes are known as efficient catalysts for the
      electrochemical reduction of CO(2) to CO, despite having overvoltages of more
      than 0.6 V. Incorporating [Ni(cyclam)](2+) into poly(allylamine) through axial
      coordination of pyridine enables the electrochemical reduction of CO(2) to CO
      near the thermodynamic potential of -0.78 V (vs. Ag/AgCl) at pH 8 with a current
      efficiency of 90 %.

PMID- 22411896
TI  - Participation and coordination in Dutch health care policy-making. A network
      analysis of the system of intermediate organizations in Dutch health care.
AB  - This study explores the system of intermediate organizations in Dutch health care
      as the crucial system to understand health care policy-making in the Netherlands.
      We argue that the Dutch health care system can be understood as a system
      consisting of distinct but inter-related policy domains. In this study, we
      analyze four such policy domains: Finances, quality of care, manpower planning
      and pharmaceuticals. With the help of network analytic techniques, we describe
      how this highly differentiated system of >200 intermediate organizations is
      structured and coordinated and what (policy) consequences can be observed with
      regard to its particular structure and coordination mechanisms. We further
      analyze the extent to which this system of intermediate organizations enables
      participation of stakeholders in policy-making using network visualization tools.
      The results indicate that coordination between the different policy domains
      within the health care sector takes place not as one would expect through
      governmental agencies, but through representative organizations such as the
      representative organizations of the (general) hospitals, the health care
      consumers and the employers' association. We further conclude that the system
      allows as well as denies a large number of potential participants access to the
      policy-making process. As a consequence, the representation of interests is not
      necessarily balanced, which in turn affects health care policy. We find that the
      interests of the Dutch health care consumers are well accommodated with the
      national umbrella organization NPCF in the lead. However, this is no safeguard
      for the overall community values of good health care since, for example, the
      interests of the public health sector are likely to be marginalized.

PMID- 22411897
TI  - Quantitative proteomic profiling identifies protein correlates to EGFR kinase
      inhibition.
AB  - Clinical oncology is hampered by lack of tools to accurately assess a patient's
      response to pathway-targeted therapies. Serum and tumor cell surface proteins
      whose abundance, or change in abundance in response to therapy, differentiates
      patients responding to a therapy from patients not responding to a therapy could
      be usefully incorporated into tools for monitoring response. Here, we posit and
      then verify that proteomic discovery in in vitro tissue culture models can
      identify proteins with concordant in vivo behavior and further, can be a valuable
      approach for identifying tumor-derived serum proteins. In this study, we use
      stable isotope labeling of amino acids in culture (SILAC) with proteomic
      technologies to quantitatively analyze the gefitinib-related protein changes in a
      model system for sensitivity to EGF receptor (EGFR)-targeted tyrosine kinase
      inhibitors. We identified 3,707 intracellular proteins, 1,276 cell surface
      proteins, and 879 shed proteins. More than 75% of the proteins identified had
      quantitative information, and a subset consisting of 400 proteins showed a
      statistically significant change in abundance following gefitinib treatment. We
      validated the change in expression profile in vitro and screened our panel of
      response markers in an in vivo isogenic resistant model and showed that these
      were markers of gefitinib response and not simply markers of phospho-EGFR
      downregulation. In doing so, we also were able to identify which proteins might
      be useful as markers for monitoring response and which proteins might be useful
      as markers for a priori prediction of response.

PMID- 22411898
TI  - High TUBB3 expression, an independent prognostic marker in patients with early
      non-small cell lung cancer treated by preoperative chemotherapy, is regulated by
      K-Ras signaling pathway.
AB  - We assessed the prognostic and predictive value of beta-tubulin III (TUBB3)
      expression, as determined by immunohistochemistry, in 412 non-small cell lung
      cancer (NSCLC) specimens from early-stage patients who received neoadjuvant
      chemotherapy (paclitaxel- or gemcitabine-based) in a phase III trial (IFCT-0002).
      We also correlated TUBB3 expression with K-Ras and EGF receptor (EGFR) mutations
      in a subset of 208 cryopreserved specimens. High TUBB3 protein expression was
      associated with nonsquamous cell carcinomas (P < 0.001) and K-Ras mutation (P <
      0.001). The 127 (30.8%) TUBB3-negative patients derived more than 1 year of
      overall survival advantage, with more than 84 months median overall survival
      versus 71.7 months for TUBB3-positive patients [HR, 1.58; 95% confidence interval
      (CI), 1.11-2.25)]. This prognostic value was confirmed in multivariate analysis
      (adjusted HR for death, 1.51; 95% CI, 1.04-2.21; P = 0.031) with a bootstrapping
      validation procedure. TUBB3 expression was associated with nonresponse to
      chemotherapy (adjusted HR, 1.31; 95% CI, 1.01-1.70; P = 0.044) but had no
      predictive value (taxane vs. gemcitabine). Taking account of these clinical
      findings, we further investigated TUBB3 expression in isogenic human bronchial
      cell lines only differing by K-Ras gene status and assessed the effect of K-Ras
      short interfering RNA (siRNA) mediated depletion, cell hypoxia, or pharmacologic
      inhibitors of K-Ras downstream effectors, on TUBB3 protein cell content. siRNA K
      Ras knockdown, inhibition of RAF/MEK (MAP-ERK kinase) and phosphoinositide 3
      kinase (PI3K)/AKT signaling, and hypoxia were shown to downregulate TUBB3
      expression in bronchial cells. This study is the first one to identify K-Ras
      mutations as determinant of TUBB3 expression, a chemoresistance marker. Our in
      vitro data deserve studies combining standard chemotherapy with anti-MEK or anti
      PI3K drugs in patients with TUBB3-overexpressing tumors.

PMID- 22411899
TI  - Obatoclax interacts synergistically with the irreversible proteasome inhibitor
      carfilzomib in GC- and ABC-DLBCL cells in vitro and in vivo.
AB  - Interactions between the irreversible proteasome inhibitor carfilzomib and the
      pan-BH3 mimetic obatoclax were examined in germinal center (GC)- and activated B
      cell-diffuse large B-cell lymphoma (ABC-DLBCL) cells. Cotreatment with minimally
      toxic concentrations of carfilzomib (i.e., 2-6 nmol/L) and subtoxic
      concentrations of obatoclax (0.05-2.0 MUmol/L) synergistically increased
      apoptosis in multiple DLBCL cell lines and increased lethality toward primary
      human DLBCL but not normal CD34(+) cells. Synergistic interactions were
      associated with sharp increases in caspase-3 activation, PARP cleavage, p-JNK
      induction, upregulation of Noxa, and AKT dephosphorylation. Combined treatment
      also diminished carfilzomib-mediated Mcl-1 upregulation whereas
      immunoprecipitation analysis revealed reduced associations between Bak and Mcl
      1/Bcl-xL and Bim and Mcl-1. The carfilzomib/obatoclax regimen triggered
      translocation, conformational change, and dimerization of Bax and activation of
      Bak. Genetic interruption of c-jun-NH(2)-kinase (JNK) and Noxa by short hairpin
      RNA knockdown, ectopic Mcl-1 expression, or enforced activation of AKT
      significantly attenuated carfilzomib/obatoclax-mediated apoptosis. Notably,
      coadministration of carfilzomib/obatoclax sharply increased apoptosis in multiple
      bortezomib-resistant DLBCL models. Finally, in vivo administration of carfilzomib
      and obatoclax to mice inoculated with SUDHL4 cells substantially suppressed tumor
      growth, activated JNK, inactivated AKT, and increased survival compared with the
      effects of single-agent treatment. Together, these findings argue that a strategy
      combining carfilzomib and obatoclax warrants attention in DLBCL.

PMID- 22411900
TI  - Cotargeting MAPK and PI3K signaling with concurrent radiotherapy as a strategy
      for the treatment of pancreatic cancer.
AB  - There is an urgent need for the development of novel therapies to treat
      pancreatic cancer, which is among the most lethal of all cancers. KRAS-activating
      mutations, which are found in more than 90% of pancreatic adenocarcinomas, drive
      tumor dependency on the Ras/MAPK and Akt signaling pathways. Radiation is
      currently being explored as a component of the standard treatment regimen for
      pancreatic cancer. This study's purpose was to test the hypothesis that MAP
      kinase kinase (MEK or MAP2K) inhibitors will offer clear therapeutic benefit when
      integrated into radiotherapy treatment regimens for treatment of this disease. We
      explored the activation of the mitogen-activated protein kinase (MAPK) and Akt
      pathways in response to radiation in multiple pancreatic tumor cell lines. Small
      molecule inhibitors of MEK (PD0325901) and Akt (API-2) were subsequently
      evaluated for their radiosensitizing potential alone and in combination. In vivo
      efficacy was tested in subcutaneous MIA-PaCa2 xenografts. Phosphorylated levels
      of extracellular signal-regulated kinase (ERK)-1/2 and Akt were found to increase
      in response to radiation treatment in our pancreatic tumor cell line panel. MEK
      inhibitor-induced radiosensitization was observed in vitro and in vivo. The
      further addition of an Akt inhibitor to the MEK inhibitor/radiation regimen
      resulted in enhanced therapeutic gain as determined by increased
      radiosensitization and tumor cell death. In conclusion, MEK inhibition results in
      growth arrest, apoptosis, and radiosensitization of multiple preclinical
      pancreatic tumor models, and the effects can be enhanced by combination with an
      Akt inhibitor. These results provide rationale for further testing of a treatment
      regimen in pancreatic cancer that combines MEK inhibition with radiation,
      optimally in conjunction with Akt inhibition.

PMID- 22411901
TI  - Update for the logicle data scale including operational code implementations.

PMID- 22411902
TI  - Life history parameters and scale-cover surface area of Aonidiella aurantii are
      altered in a mating disruption environment: implications for biological control.
AB  - BACKGROUND: In recent years, environmentally safe measures to control the
      California red scale (CRS), Aonidiella aurantii (Maskell), have been successfully
      implemented. These measures include mating disruption (MD) and biological
      control. The goal of this study was to examine the effect of high concentrations
      of the CRS sex pheromone on its life history parameters and scale-cover surface
      area under controlled laboratory conditions. RESULTS: The developmental time of
      both males and females of CRS increased with exposure to airborne pheromone. MD
      had an effect on both the total number of progeny and on the crawler production
      period for females. Accordingly, demographic parameters such as net fecundity
      (R(0) ) and intrinsic rate of increase (r(m) ) were significantly lower in the
      pheromone-treated populations. The largest scale-cover surface areas were
      observed in the CRS reared in the pheromone environment. CONCLUSION: A clear
      influence of airborne pheromone on the biology of CRS has been demonstrated. In
      addition to the classical mating disruption benefits of this technique,
      additional benefits, such as increase in the duration of exposure to natural
      enemies and increase in size, which benefits some species of parasitoids, have
      been confirmed.

PMID- 22411903
TI  - Exploring aligned-carbon-nanotubes@polyaniline arrays on household Al as
      supercapacitors.
AB  - Herein, we demonstrate a new approach towards the construction of supercapacitors
      consisting of carbon nanotubes (CNTs) and conducting polymers (ECPs) with high
      specific power, high specific energy, and stable cycling performance through a 3D
      design of a thin film of polyaniline (PANI) on an aligned small carbon nanotube
      (ACNT) array on household Al foils. The thin-film strategy is used to fully
      exploit the specific capacitance of PANI, and obtain regular pores, strong
      interaction between PANI and CNTs, and reduced electrical resistance for the
      electrodes. A facile process is developed to fabricate a highly flexible
      supercapacitor using this binder-free composite on household Al foil as the
      current collector. It exhibits high specific energy of 18.9 Wh kg(-1) , high
      maximum specific power of 11.3 kW kg(-1) of the active material in an aqueous
      electrolyte at 1.0 A g(-1) , and excellent rate performance and cycling
      stability. A high specific energy of 72.4 Wh kg(-1) , a high maximum specific
      power of 24.9 kW kg(-1) , and a good cycling performance of the active material
      are obtained in an organic electrolyte.

PMID- 22411904
TI  - Blood type and ovarian reserve.

PMID- 22411905
TI  - OMIP-007: phenotypic analysis of human natural killer cells.

PMID- 22411906
TI  - Nematicidal fluorescent pseudomonads for the in vitro and in vivo suppression of
      root knot (Meloidogyne incognita) of Capsicum annuum L.
AB  - BACKGROUND: Considerable attention has been paid to plant-growth-promoting
      rhizobacteria (PGPR), especially the fluorescent group of Pseudomonas species, as
      the best alternatives to chemicals for facilitating ecofriendly biological
      control of soil- and seedborne microorganisms. On the basis of their novel plant
      growth-promoting attributes, two rhizobacteria Pseudomonas aeruginosa VP1 and VP2
      selected out of over 63 isolates from the rhizosphere of chilli (Capsicum annuum)
      were identified as potential candidates for biocontrol of the root-knot nematode
      Meloidogyne incognita on chilli. RESULTS: The nematicidal activity of both
      strains was evaluated in vitro and in vivo for their efficacy against M.
      incognita. P. aeruginosa VP2 exhibited strong nematicidal activity in comparison
      with VP1, based on the in vitro killing of the second-stage juveniles (J2) of M.
      incognita. Seed bacterisation with both strains VP1 and VP2 was able to manage
      root-knot M. incognita on chilli (C. annuum) in a pot trial study. Increase in
      root and shoot length and in fresh and dry weight of root and shoot and reduction
      in the root-knot index over the control were attained. In overall performance,
      VP2 was 29.5% more effective than VP1, and about 30% more effective than the
      control (non-bacterised). CONCLUSION: The application of P. aeruginosa VP1 and P.
      aeruginosa VP2 controls the development of M. incognita in C. annuum, and hence
      they are recommended as efficient plant growth promotors and biocontrolling
      agents for raising healthy crop of C. annuum that can promote the growth of
      plants and reduce the nematode (M. incognita) population.

PMID- 22411907
TI  - Enabling user-guided segmentation and tracking of surface-labeled cells in time
      lapse image sets of living tissues.
AB  - To study the process of morphogenesis, one often needs to collect and segment
      time-lapse images of living tissues to accurately track changing cellular
      morphology. This task typically involves segmenting and tracking tens to hundreds
      of individual cells over hundreds of image frames, a scale that would certainly
      benefit from automated routines; however, any automated routine would need to
      reliably handle a large number of sporadic, and yet typical problems (e.g.,
      illumination inconsistency, photobleaching, rapid cell motions, and drift of
      focus or of cells moving through the imaging plane). Here, we present a
      segmentation and cell tracking approach based on the premise that users know
      their data best-interpreting and using image features that are not accounted for
      in any a priori algorithm design. We have developed a program, SeedWater
      Segmenter, that combines a parameter-less and fast automated watershed algorithm
      with a suite of manual intervention tools that enables users with little to no
      specialized knowledge of image processing to efficiently segment images with near
      perfect accuracy based on simple user interactions.

PMID- 22411908
TI  - Dual effect of inorganic polymeric phosphate/polyphosphate on osteoblasts and
      osteoclasts in vitro.
AB  - Inorganic polymeric phosphate/polyphosphate (polyP) is a natural polymer existing
      in both pro- and eukaryotic systems. In the present study the effect of polyP as
      well as of polyP supplied in a stoichiometric ratio of 2 m polyP:1 m CaCl2 [polyP
      (Ca(2+) complex)] on the osteoblast-like SaOS-2 cells and the osteoclast-like RAW
      264.7 cells was determined. Both polymers are non-toxic for these cells up to a
      concentration of 100 um. In contrast to polyP, polyP (Ca(2+) complex)
      significantly induced hydroxyapatite formation at a concentration > 10 um, as
      documented by alizarin red S staining and scanning electron microscopic (SEM)
      inspection. Furthermore, polyP (Ca(2+) complex) triggered in SaOS-2 cells
      transcription of BMP2 (bone morphogenetic protein 2), a cytokine involved in
      maturation of hydroxyapatite-forming cells. An additional activity of polyP
      (Ca(2+) complex) is described by showing that this polymer impairs
      osteoclastogenesis. At concentrations > 10 um polyP (Ca(2+) complex) slows down
      the progression of RAW 264.7 cells to functional osteoclasts, as measured by the
      expression of TRAP (tartrate-resistant acid phosphatase). Finally, it is shown
      that 10-100 um polyP (Ca(2+) complex) inhibited phosphorylation of IkappaBalpha
      by the respective kinase in RAW 264.7 cells. We concluded that polyP (Ca(2+)
      complex) displays a dual effect on bone metabolizing cells. It promotes
      hydroxyapatite formation in SaOS-2 cells (osteoblasts) and impairs maturation of
      the osteoclast-related RAW 264.7 cells.

PMID- 22411909
TI  - Sensitivity to silthiofam, tebuconazole and difenoconazole of Gaeumannomyces
      graminis var. tritici isolates from China.
AB  - BACKGROUND: Wheat take-all caused by Gaeumannomyces graminis var. tritici (Ggt)
      has become an emerging threat to wheat production in the last few years.
      Silthiofam is very effective against Ggt, and recently it has been widely used
      for the control of take-all in China. However, farmers have noted a decline in
      control efficacy with this compound in some wheat fields, suggesting that the
      pathogen may have developed resistance to silthiofam. RESULTS: Of the 66 Ggt
      isolates collected from different locations in China, 27 were resistant to
      silthiofam. There was no cross-resistance between silthiofam and tecuconazole or
      difenoconazole. The effectiveness of silthiofam in controlling take-all was
      compromised on wheat inoculated with silthiofam-resistant isolates. Based on the
      DNA fingerprinting generated by microsatellite PCR, two predominant genetic
      clusters were found among these isolates and were clearly associated with the
      sensitivity to silthiofam. CONCLUSION: Silthiofam has a high risk in the
      development of resistance in Ggt. Tebuconazole and difenoconazole show great
      potential for control of take-all on wheat. Results from this study provide
      useful information for take-all control and the management of fungicide
      resistance.

PMID- 22411910
TI  - Intracellular stability of 2'-OMe-4'-thioribonucleoside modified siRNA leads to
      long-term RNAi effect.
AB  - Chemically modified siRNAs are expected to have resistance toward nuclease
      degradation and good thermal stability in duplex formation for in vivo
      applications. We have recently found that 2'-OMe-4'-thioRNA, a hybrid chemical
      modification based on 2'-OMeRNA and 4'-thioRNA, has high hybridization affinity
      for complementary RNA and significant resistance toward degradation in human
      plasma. These results prompted us to develop chemically modified siRNAs using 2'
      OMe-4'-thioribonucleosides for therapeutic application. Effective modification
      patterns were screened with a luciferase reporter assay. The best modification
      pattern of siRNA, which conferred duration of the gene-silencing effect without
      loss of RNAi activity, was identified. Quantification of the remaining siRNA in
      HeLa-luc cells using a Heat-in-Triton (HIT) qRT-PCR revealed that the
      intracellular stability of the siRNA modified with 2'-OMe-4'-thioribonucleosides
      contributed significantly to the duration of its RNAi activity.

PMID- 22411912
TI  - Soy protein films for wound-healing applications: antibiotic release, bacterial
      inhibition and cellular response.
AB  - Use of naturally derived materials is becoming widespread in the biomedical
      field. Soy protein has advantages over the various types of natural proteins
      employed for biomedical applications, due to its low price, non-animal origin and
      relatively long storage time and stability. In the current study, soy protein
      isolate (SPI) was investigated as a matrix for wound-dressing applications. The
      antibiotic drug gentamicin was incorporated into the matrix for local controlled
      release and thus continuous bactericidal effect. Homogeneous high-quality films
      were cast from aqueous solutions and tested for the effects of gentamicin release
      on bacterial inhibition. The cytotoxicity and in vitro biocompatibility of these
      films were also examined. The gentamicin release profiles exhibited a moderate
      burst effect followed by a decreasing release rate, which was maintained for at
      least 4 weeks, thus enabling a suitable bacterial inhibition effect. The
      materials released from the films during an indirect cytotoxicity test were found
      to be safe, except for a slight inhibitory effect in the presence of high
      concentrations of glycerol. The biocompatibility test showed confluent cell
      cultures in close proximity to the SPI films. It is clear that these new
      antibiotic-eluting SPI films exhibit a high potential for use as wound dressings.

PMID- 22411911
TI  - How much can we learn about the function of bacterial rRNA modification by mining
      large-scale experimental datasets?
AB  - Modification of ribosomal RNA is ubiquitous among living organisms. Its
      functional role is well established for only a limited number of modified
      nucleotides. There are examples of rRNA modification involvement in the gene
      expression regulation in the cell. There is a need for large data set analysis in
      the search for potential functional partners for rRNA modification. In this
      study, we extracted phylogenetic profile, genome neighbourhood, co-expression and
      phenotype profile and co-purification data regarding Escherichia coli rRNA
      modification enzymes from public databases. Results were visualized as graphs
      using Cytoscape and analysed. Majority linked genes/proteins belong to
      translation apparatus. Among co-purification partners of rRNA modification
      enzymes are several candidates for experimental validation. Phylogenetic
      profiling revealed links of pseudouridine synthetases with RF2, RsmH with
      translation factors IF2, RF1 and LepA and RlmM with RdgC. Genome neighbourhood
      connections revealed several putative functionally linked genes, e.g. rlmH with
      genes coding for cell wall biosynthetic proteins and others. Comparative analysis
      of expression profiles (Gene Expression Omnibus) revealed two main associations,
      a group of genes expressed during fast growth and association of rrmJ with heat
      shock genes. This study might be used as a roadmap for further experimental
      verification of predicted functional interactions.

PMID- 22411913
TI  - Planning and designing the care transitions innovation (C-Train) for uninsured
      and Medicaid patients.
AB  - BACKGROUND: Uninsured and Medicaid patients are particularly vulnerable as they
      transition from hospital to home. Transitional care improvement programs require
      time and capital, incentives for which may be unclear for those lacking a third
      party payor. This article describes our experience developing a hospital-funded
      transitional care program for uninsured and Medicaid patients. METHODS: We
      performed an inpatient needs assessment, convened multi-stakeholder work groups,
      and engaged institutional change-agents to inform program development and a
      business case. RESULTS: We mapped needs to specific program elements, including a
      transitional care nurse, pharmacy consult and provision of medications for
      uninsured patients, medical home linkages including community payment for medical
      homes, and monthly quality improvement meetings. A business case was informed by
      local needs and utilization data, and compelled the hospital to invest in up
      front resources for this population. DISCUSSION: We are studying our program's
      impact on 30-day readmission and emergency department rates through a clustered,
      randomized controlled trial. Lessons from our experience may be useful to others
      aiming to improve care for socioeconomically disadvantaged patients.

PMID- 22411914
TI  - The micro-RNA 199b-5p regulatory circuit involves Hes1, CD15, and epigenetic
      modifications in medulloblastoma.
AB  - Micro-RNA (miR) 199b-5p targets Hes1 in medulloblastoma, one of the downstream
      effectors of both the canonical Notch and noncanonical Sonic Hedgehog pathways.
      In medulloblastoma patients, expression of miR-199b-5p is significantly decreased
      in metastatic cases, thus suggesting a downregulation mechanism. We studied this
      mechanism, which is mediated mostly by Hes1 and epigenetic promoter
      modifications. The miR-199b-5p promoter region was characterized, which
      identified a Hes1 binding site, thus demonstrating a negative feedback loop of
      regulation. MiR-199b-5p was shown to be downregulated in several medulloblastoma
      cell lines and in tumors by epigenetic methylation of a cytosine-phosphate
      guanine island upstream of the miR-199b-5p promoter. Furthermore, the cluster of
      differention (CD) carbohydrate antigen CD15, a marker of medulloblastoma tumor
      propagating cells, is an additional direct target of miR-199b-5p. Most
      importantly, regulation of miR-199b-5p expression in these CD15+/CD133+ tumor
      propagating cells was influenced by only Hes1 expression and not by any
      epigenetic mechanism of regulation. Moreover, reverse-phase protein array
      analysis showed both the Akt and extracellular-signal-regulated kinase pathways
      as being mainly negatively regulated by miR-199b-5p expression in several
      medulloblastoma cell lines and in primary cell cultures. We present here the
      finely tuned regulation of miR-199b-5p in medulloblastoma, underlining its
      crucial role by its additional targeting of CD15.

PMID- 22411917
TI  - The role of dipeptidyl peptidase-4 inhibitors.

PMID- 22411915
TI  - dSir2 deficiency in the fatbody, but not muscles, affects systemic insulin
      signaling, fat mobilization and starvation survival in flies.
AB  - Sir2 is an evolutionarily conserved NAD+ dependent protein. Although, SIRT1 has
      been implicated to be a key regulator of fat and glucose metabolism in mammals,
      the role of Sir2 in regulating organismal physiology, in invertebrates, is
      unclear. Drosophila has been used to study evolutionarily conserved nutrient
      sensing mechanisms, however, the molecular and metabolic pathways downstream to
      Sir2 (dSir2) are poorly understood. Here, we have knocked down endogenous dSir2
      in a tissue specific manner using gene-switch gal4 drivers. Knockdown of dSir2 in
      the adult fatbody leads to deregulated fat metabolism involving altered
      expression of key metabolic genes. Our results highlight the role of dSir2 in
      mobilizing fat reserves and demonstrate that its functions in the adult fatbody
      are crucial for starvation survival. Further, dSir2 knockdown in the fatbody
      affects dilp5 (insulin-like-peptide) expression, and mediates systemic effects of
      insulin signaling. This report delineates the functions of dSir2 in the fatbody
      and muscles with systemic consequences on fat metabolism and insulin signaling.
      In conclusion, these findings highlight the central role that fatbody dSir2 plays
      in linking metabolism to organismal physiology and its importance for survival.

PMID- 22411918
TI  - Healthier ageing.

PMID- 22411919
TI  - Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in
      the clinical setting: systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the efficacy and safety of dipeptidyl peptidase-4 (DPP-4)
      inhibitors compared with metformin as monotherapy, or with other commonly used
      hypoglycaemic drugs combined with metformin, in adults with type 2 diabetes
      mellitus. DESIGN: Systematic review and meta-analysis of randomised controlled
      trials. DATA SOURCES: Medline, Embase, the Cochrane Library, conference
      proceedings, trial registers, and drug manufacturers' websites. ELIGIBILITY
      CRITERIA: Randomised controlled trials of adults with type 2 diabetes mellitus
      that compared a DPP-4 with metformin as monotherapy or with a sulfonylurea,
      pioglitazone, a glucagon-like peptide-1 (GLP-1) agonist, or basal insulin
      combined with metformin on the change from baseline in glycated haemoglobin
      (HbA(1c)). DATA EXTRACTION: The primary outcome was the change in HbA(1c).
      Secondary outcomes included the proportion of patients achieving the goal of
      HbA(1c) <7%, the change in body weight, discontinuation rate because of any
      adverse event, occurrence of any serious adverse event, all cause mortality, and
      incidence of hypoglycaemia, nasopharyngitis, urinary tract infection, upper
      respiratory infection, nausea, vomiting, and diarrhoea. RESULTS: 27 reports of 19
      studies including 7136 patients randomised to a DPP-4 inhibitor and 6745 patients
      randomised to another hypoglycaemic drug were eligible for the systematic review
      and meta-analysis. Overall risk of bias for the primary outcome was low in three
      reports, unclear in nine, and high in 14. Compared with metformin as monotherapy,
      DPP-4 inhibitors were associated with a smaller decline in HbA(1c) (weighted mean
      difference 0.20, 95% confidence interval 0.08 to 0.32) and in body weight (1.5,
      0.9 to 2.11). As a second line treatment, DPP-4 inhibitors were inferior to GLP-1
      agonists (0.49, 0.31 to 0.67) and similar to pioglitazone (0.09, -0.07 to 0.24)
      in reducing HbA(1c) and had no advantage over sulfonylureas in the attainment of
      the HbA(1c) goal (risk ratio in favour of sulfonylureas 1.06, 0.98 to 1.14). DPP
      4 inhibitors had a favourable weight profile compared with sulfonylureas
      (weighted mean difference -1.92, -2.34 to -1.49) or pioglitazone (-2.96, -4.13 to
      -1.78), but not compared with GLP-1 agonists (1.56, 0.94 to 2.18). Only a minimal
      number of hypoglycaemias were observed in any treatment arm in trials comparing a
      DPP-4 inhibitor with metformin as monotherapy or with pioglitazone or a GLP-1
      agonist as second line treatment. In most trials comparing a DPP-4 inhibitor with
      sulfonylureas combined with metformin, the risk for hypoglycaemia was higher in
      the group treated with a sulfonylurea. Incidence of any serious adverse event was
      lower with DPP-4 inhibitors than with pioglitazone. Incidence of nausea,
      diarrhoea, and vomiting was higher in patients receiving metformin or a GLP-1
      agonist than in those receiving a DPP-4 inhibitor. Risk for nasopharyngitis,
      upper respiratory tract infection, or urinary tract infection did not differ
      between DPP-4 inhibitors and any of the active comparators. CONCLUSION: In
      patients with type 2 diabetes who do not achieve the glycaemic targets with
      metformin alone, DPP-4 inhibitors can lower HbA(1c), in a similar way to
      sulfonylureas or pioglitazone, with neutral effects on body weight. Increased
      unit cost, which largely exceeds that of the older drugs, and uncertainty about
      their long term safety, however, should also be considered.

PMID- 22411921
TI  - A reduced risk of Alzheimer's disease in those who survive cancer.

PMID- 22411920
TI  - Inverse association between cancer and Alzheimer's disease: results from the
      Framingham Heart Study.
AB  - OBJECTIVES: To relate cancer since entry into the Framingham Heart Study with the
      risk of incident Alzheimer's disease and to estimate the risk of incident cancer
      among participants with and without Alzheimer's disease. DESIGN: Community based
      prospective cohort study; nested age and sex matched case-control study. SETTING:
      Framingham Heart Study, USA. PARTICIPANTS: 1278 participants with and without a
      history of cancer who were aged 65 or more and free of dementia at baseline (1986
      90). MAIN OUTCOME MEASURES: Hazard ratios and 95% confidence intervals for the
      risks of Alzheimer's disease and cancer. RESULTS: Over a mean follow-up of 10
      years, 221 cases of probable Alzheimer's disease were diagnosed. Cancer survivors
      had a lower risk of probable Alzheimer's disease (hazard ratio 0.67, 95%
      confidence interval 0.47 to 0.97), adjusted for age, sex, and smoking. The risk
      was lower among survivors of smoking related cancers (0.26, 0.08 to 0.82) than
      among survivors of non-smoking related cancers (0.82, 0.57 to 1.19). In contrast
      with their decreased risk of Alzheimer's disease, survivors of smoking related
      cancer had a substantially increased risk of stroke (2.18, 1.29 to 3.68). In the
      nested case-control analysis, participants with probable Alzheimer's disease had
      a lower risk of subsequent cancer (0.39, 0.26 to 0.58) than reference
      participants, as did participants with any Alzheimer's disease (0.38) and any
      dementia (0.44). CONCLUSIONS: Cancer survivors had a lower risk of Alzheimer's
      disease than those without cancer, and patients with Alzheimer's disease had a
      lower risk of incident cancer. The risk of Alzheimer's disease was lowest in
      survivors of smoking related cancers, and was not primarily explained by survival
      bias. This pattern for cancer is similar to that seen in Parkinson's disease and
      suggests an inverse association between cancer and neurodegeneration.

PMID- 22411922
TI  - Stakeholders appeal for more kidney donations in Europe.

PMID- 22411923
TI  - Expert group is to examine the effect and value of the NHS constitution.

PMID- 22411924
TI  - Lansley must publish register of risks posed by NHS changes, rules tribunal.

PMID- 22411925
TI  - Helical and tubular lipid microstructures that are electroless-coated with
      CoNiReP for wireless magnetic manipulation.
AB  - Hybrid magnetic phospholipidic-based tubular and helical microagents are
      wirelessly manipulated by means of a 5-DOF electromagnetic system. Two different
      strategies are used to manipulate these nanostructures in simulated biologic
      capillaries. Tubules are pulled by applying magnetic field gradients and oriented
      by magnetic fields. Helices exhibit a cork-screw motion similar to the swimming
      strategy used by motile bacteria such as E. coli.

PMID- 22411926
TI  - Expression of concern.

PMID- 22411928
TI  - Elastin degradation is associated with progressive aortic stiffening and all
      cause mortality in predialysis chronic kidney disease.
AB  - In the large conduit arteries, elastin is important in maintaining vascular
      compliance. Studies in animal models suggest that elastin degradation may promote
      arteriosclerotic vascular changes. There is already a well-established link
      between aortic stiffening and mortality in the general population and in patients
      undergoing dialysis. Elastin degradation is mediated by several proteases,
      including matrix metalloproteinase 2 and cathepsin S. Elastin turnover may be
      inferred by measuring serum levels of elastin-derived peptides. We analyzed the
      serum concentration of these biomarkers, their endogenous inhibitors, and aortic
      pulse wave velocity in 200 patients with stages 3 and 4 chronic kidney disease
      and then serially in a subgroup of 65 patients over 36 months. Serum matrix
      metalloproteinase 2, cathepsin S, and elastin-derived peptide levels were
      independently associated with baseline aortic pulse wave velocity and changes in
      stiffness over the follow-up period. Higher matrix metalloproteinase 2 and
      elastin-derived peptide levels were also independently associated with
      preexisting cardiovascular disease. In multivariable Cox regression, higher serum
      elastin-derived peptide levels were independently associated with increased all
      cause mortality (hazard ratio per SD increase=1.78; P=0.021). In predialysis
      chronic kidney disease, elastin degradation is an important determinant of
      arterial stiffness and is associated with all-cause mortality.

PMID- 22411927
TI  - Altered functioning of both renal dopamine D1 and angiotensin II type 1 receptors
      causes hypertension in old rats.
AB  - Activation of renal dopamine D1 (D1R) and angiotensin II type 1 receptors
      (AT(1)Rs) influences the activity of proximal tubular sodium transporter Na,K
      ATPase and maintains sodium homeostasis and blood pressure. We reported recently
      that diminished D1R and exaggerated AT(1)R functions are associated with
      hypertension in old Fischer 344 * Brown Norway F1 (FBN) rats, and oxidative
      stress plays a central role in this phenomenon. Here we studied the mechanisms of
      age-associated increase in oxidative stress on diminished D1R and exaggerated
      AT(1)R functions in the renal proximal tubules of control and antioxidant Tempol
      treated adult and old FBN rats. Although D1R numbers and D1R agonist SKF38393
      mediated stimulation of [(35)S]-GTPgammaS binding (index of D1R activation) were
      lower, G protein-coupled receptor kinase 4 (kinase that uncouples D1R) levels
      were higher in old FBN rats. Tempol treatment restored D1R numbers and G protein
      coupling and reduced G protein-coupled receptor kinase 4 levels in old FBN rats.
      Angiotensin II-mediated stimulation of [(35)S]-GTPgammaS binding and Na,K-ATPase
      activity were higher in old FBN rats, which were also restored with Tempol
      treatment. We also measured renal AT(1)R function in adult and old Fischer 344
      (F344) rats, which, despite exhibiting an age-related increase in oxidative
      stress and diminished renal D1R function, are normotensive. We found that
      diuretic and natriuretic responses to candesartan (indices of AT(1)R function)
      were similar in F344 rats, a likely explanation for the absence of age-associated
      hypertension in these rats. Perhaps, alterations in both D1R (diminished) and
      AT(1)R (exaggerated) functions are necessary for the development of age
      associated hypertension, as seen in old FBN rats.

PMID- 22411929
TI  - Testosterone and blood pressure: is the decreased sodium excretion the missing
      link?

PMID- 22411930
TI  - Adjunctive use of eptifibatide for complication management during elective
      neuroendovascular procedures.
AB  - OBJECTIVE: A rare complication of neuroendovascular procedures is acute
      thromboembolism. In the setting of intraprocedural or periprocedural embolism,
      thrombolytics present a potentially useful therapeutic strategy. A series of
      patients in whom eptifibatide (a platelet glycoprotein IIb/IIIa receptor
      inhibitor) was used in the treatment of iatrogenic thromboembolic events
      occurring during elective neuroendovascular procedures is described. METHODS:
      Consecutive cases between May 2009 and July 2011 in which eptifibatide was
      administered were identified and individually reviewed for inclusion in this
      study (n=12). All study patients received a uniform, weight based bolus dose of
      180 MUg/kg of eptifibatide administered either intra-arterially through the guide
      catheter or intravenously. Eptifibatide infusion (2 MUg/kg/min) for 24 h after
      bolus dose administration was continued at the discretion of the surgeon.
      Procedural details are described and illustrative cases presented. RESULTS: Three
      major categories of thromboembolic events were isolated in the course of review
      of study cases: acute focal neurological decline and no radiographic findings of
      flow limitation (eight patients), radiographic findings with or without symptoms
      (two patients) and persistent particulate debris during flow reversal as part of
      a carotid revascularization procedure (two patients). Following eptifibatide
      administration, no patient experienced hemorrhagic complications, and neurologic
      improvement to baseline level was noted in 10 of 12 patients. CONCLUSION:
      Eptifibatide may be an effective therapeutic strategy in the event of
      thromboembolism during elective neuroendovascular procedures.

PMID- 22411931
TI  - Mentor mothers to prevent mother-to-child transmission of HIV.

PMID- 22411932
TI  - A retrospective cross-sectional study of risk factors and clinical spectrum of
      children admitted to hospital with pandemic H1N1 influenza as compared to
      influenza A.
AB  - OBJECTIVE: To compare risk factors for severe disease as measured by admission to
      hospital and intensive care unit (ICU) and other clinical outcomes in children
      with pandemic H1N1 (pH1N1) versus those with seasonal influenza. DESIGN:
      Retrospective analysis of children admitted to hospital with pH1N1 versus
      seasonal influenza A. SETTING: Canadian tertiary referral children's hospital.
      PARTICIPANTS: All laboratory-identified cases of pH1N1 in children younger than
      18 years admitted to hospital in 2009 (n=176) and all seasonal influenza A cases
      admitted to hospital from influenza seasons 2004-2005 to 2008-2009 (n=200).
      Children with onset of symptoms more than 3 days after admission were excluded.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes include admission to
      hospital and ICU and need for mechanical ventilation. Secondary outcomes include
      length of stay in hospital and duration of supplemental oxygen requirement.
      RESULTS: Children admitted with pH1N1 were older than seasonal influenza A
      admissions (hospital admission: 6.5 vs 3.3 years, p<0.01; ICU admission: 7.3 vs
      3.6 years, p=0.02). Children hospitalised with pH1N1 were more likely to have a
      pre-existing diagnosis of asthma (15% vs 5%, p<0.01); however, there was no
      difference in the severity of pre-existing asthma between the two groups. After
      controlling for obesity, asthma (OR 4.59, 95% CI 1.42 to 14.81) and age >=5 years
      (OR 2.87, 95% CI 1.60 to 5.16) were more common risk factors in admitted children
      with pH1N1. Asthma was a significant predictor of the need for intensive care in
      patients with pH1N1 (OR 4.56, 95% CI 1.16 to 17.89) but not in patients with
      seasonal influenza A. CONCLUSION: While most pH1N1 cases presented with classic
      influenza-like symptoms, risk factors for severe pH1N1 disease differed from
      seasonal influenza A. Older age and asthma were associated with increased
      admission to hospital and ICU for children with pH1N1.

PMID- 22411933
TI  - Kidney failure related to broad-spectrum antibiotics in critically ill patients:
      secondary end point results from a 1200 patient randomised trial.
AB  - OBJECTIVES: To explore whether a strategy of more intensive antibiotic therapy
      leads to emergence or prolongation of renal failure in intensive care patients.
      DESIGN: Secondary analysis from a randomised antibiotic strategy trial (the
      Procalcitonin And Survival Study). The randomised arms were conserved from the
      primary trial for the main analysis. SETTING: Nine mixed surgical/medical
      intensive care units across Denmark. PARTICIPANTS: 1200 adult intensive care
      patients, 18+ years, expected to stay +24 h. EXCLUSION CRITERIA: bilirubin >40
      mg/dl, triglycerides >1000 mg/dl, increased risk from blood sampling,
      pregnant/breast feeding and psychiatric patients. INTERVENTIONS: Patients were
      randomised to guideline-based therapy ('standard-exposure' arm) or to guideline
      based therapy supplemented with antibiotic escalation whenever procalcitonin
      increased on daily measurements ('high-exposure' arm). MAIN OUTCOME MEASURES:
      Primary end point: estimated glomerular filtration rate (eGFR) <60 ml/min/1.73
      m(2). Secondary end points: (1) delta eGFR after starting/stopping a drug and (2)
      RIFLE criterion Risk 'R', Injury 'I' and Failure 'F'. Analysis was by intention
      to treat. RESULTS: 28-day mortality was 31.8% and comparable (Jensen et al, Crit
      Care Med 2011). A total of 3672/7634 (48.1%) study days during follow-up in the
      high-exposure versus 3016/6949 (43.4%) in the 'standard-exposure arm were spent
      with eGFR <60 ml/min/1.73 m(2), p<0.001. In a multiple effects model, 3
      piperacillin/tazobactam was identified as causing the lowest rate of renal
      recovery of all antibiotics used: 1.0 ml/min/1.73 m(2)/24 h while exposed to this
      drug (95% CI 0.7 to 1.3 ml/min/1.73 m(2)/24 h) vs meropenem: 2.9 ml/min/1.73
      m(2)/24 h (2.5 to 3.3 ml/min/1.73 m(2)/24 h)); after discontinuing
      piperacillin/tazobactam, the renal recovery rate increased: 2.7 ml/min/1.73
      m(2)/24 h (2.3 to 3.1 ml/min/1.73 m(2) /24 h)). eGFR <60 ml/min/1.73 m(2) in the
      two groups at entry and at last day of follow-up was 57% versus 55% and 41%
      versus 39%, respectively. CONCLUSIONS: Piperacillin/tazobactam was identified as
      a cause of delayed renal recovery in critically ill patients. This nephrotoxicity
      was not observed when using other beta-lactam antibiotics. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00271752.

PMID- 22411935
TI  - MR imaging evaluation of abdominal pain during pregnancy: appendicitis and other
      nonobstetric causes.
AB  - Clinical diagnosis of the cause of abdominal pain in a pregnant patient is
      particularly difficult because of multiple confounding factors related to normal
      pregnancy. Magnetic resonance (MR) imaging is useful in evaluation of abdominal
      pain during pregnancy, as it offers the benefit of cross-sectional imaging
      without ionizing radiation or evidence of harmful effects to the fetus. MR
      imaging is often performed specifically for diagnosis of possible appendicitis,
      which is the most common illness necessitating emergency surgery in pregnant
      patients. However, it is important to look for pathologic processes outside the
      appendix that may be an alternative source of abdominal pain. Numerous entities
      other than appendicitis can cause abdominal pain during pregnancy, including
      processes of gastrointestinal, hepatobiliary, genitourinary, vascular, and
      gynecologic origin. MR imaging is useful in diagnosing the cause of abdominal
      pain in a pregnant patient because of its ability to safely demonstrate a wide
      range of pathologic conditions in the abdomen and pelvis beyond appendicitis.

PMID- 22411934
TI  - Inflammaging: disturbed interplay between autophagy and inflammasomes.
AB  - Inflammaging refers to a low-grade pro-inflammatory phenotype which accompanies
      aging in mammals. The aging process is associated with a decline in autophagic
      capacity which impairs cellular housekeeping, leading to protein aggregation and
      accumulation of dysfunctional mitochondria which provoke reactive oxygen species
      (ROS) production and oxidative stress. Recent studies have clearly indicated that
      the ROS production induced by damaged mitochondria can stimulate intracellular
      danger-sensing multiprotein platforms called inflammasomes. Nod-like receptor 3
      (NLRP3) can be activated by many danger signals, e.g. ROS, cathepsin B released
      from destabilized lysosomes and aggregated proteins, all of which evoke cellular
      stress and are involved in the aging process. NLRP3 activation is also enhanced
      in many age-related diseases, e.g. atherosclerosis, obesity and type 2 diabetes.
      NLRP3 activates inflammatory caspases, mostly caspase-1, which cleave the
      inactive precursors of IL-1beta and IL-18 and stimulate their secretion.
      Consequently, these cytokines provoke inflammatory responses and accelerate the
      aging process by inhibiting autophagy. In conclusion, inhibition of autophagic
      capacity with aging generates the inflammaging condition via the activation of
      inflammasomes, in particular NLRP3. We will provide here a perspective on the
      current research of the ROS-dependent activation of inflammasomes triggered by
      the decline in autophagic cleansing of dysfunctional mitochondria.

PMID- 22411936
TI  - Migration of intrauterine devices: radiologic findings and implications for
      patient care.
AB  - Intrauterine devices (IUDs) are a commonly used form of contraception worldwide.
      However, migration of the IUD from its normal position in the uterine fundus is a
      frequently encountered complication, varying from uterine expulsion to
      displacement into the endometrial canal to uterine perforation. Different sites
      of IUD translocation vary in terms of their clinical significance and subsequent
      management, and the urgency of communicating IUD migration to the clinician is
      likewise variable. Expulsion or intrauterine displacement of the IUD leads to
      decreased contraceptive efficacy and should be clearly communicated, since it
      warrants IUD replacement to prevent unplanned pregnancy. Embedment of the IUD
      into the myometrium can usually be managed in the outpatient clinical setting but
      occasionally requires hysteroscopic removal. Complete uterine perforation, in
      which the IUD is partially or completely within the peritoneal cavity, requires
      surgical management, and timely and direct communication with the clinician is
      essential in such cases. Careful evaluation for intraabdominal complications is
      also important, since they may warrant urgent or emergent surgical intervention.
      The radiologist plays an important role in the diagnosis of IUD migration and
      should be familiar with its appearance at multiple imaging modalities.

PMID- 22411937
TI  - Dual-energy CT with single- and dual-source scanners: current applications in
      evaluating the genitourinary tract.
AB  - Several promising clinical applications for dual-energy computed tomography (CT)
      in genitourinary imaging have been reported. Dual-energy CT not only provides
      excellent morphologic detail but also can supply material-specific and
      quantitative information that may be particularly useful in genitourinary
      imaging. Dual-energy CT has unique capabilities for characterizing renal lesions
      by quantifying iodine content and helping identify the mineral contents of renal
      stones, information that is important for patient care. Virtual unenhanced images
      reconstructed from dual-energy CT datasets can be useful for detecting calculi
      within the iodine-filled urinary collecting system, potentially reducing the need
      for an unenhanced scanning phase at CT urography. Although the underlying
      principles of dual-energy CT are the same regardless of scanner type, single
      source dual-energy scanners with fast kilovoltage switching differ from dual
      source dual-energy scanners both in image data acquisition and in processing
      methods; an understanding of these differences may help optimize dual-energy CT
      genitourinary protocols. Dual-energy CT performed with a dual-source scanner or
      with a single-source scanner with fast kilovoltage switching also has some
      important limitations. Further advances in scanning protocols and refinement of
      processing techniques to reduce image noise may lead to more widespread use of
      dual-energy CT.

PMID- 22411938
TI  - Urinary bladder cancer: role of MR imaging.
AB  - Urinary bladder cancer is a heterogeneous disease with a variety of pathologic
      features, cytogenetic characteristics, and natural histories. It is the fourth
      most common cancer in males and the tenth most common cancer in females. Urinary
      bladder cancer has a high recurrence rate, necessitating long-term surveillance
      after initial therapy. Early detection is important, since up to 47% of bladder
      cancer-related deaths may have been avoided. Conventional computed tomography
      (CT) and magnetic resonance (MR) imaging are only moderately accurate in the
      diagnosis and local staging of bladder cancer, with cystoscopy and pathologic
      staging remaining the standards of reference. However, the role of newer MR
      imaging sequences (eg, diffusion-weighted imaging) in the diagnosis and local
      staging of bladder cancer is still evolving. Substantial advances in MR imaging
      technology have made multiparametric MR imaging a feasible and reasonably
      accurate technique for the local staging of bladder cancer to optimize treatment.
      In addition, whole-body CT is the primary imaging technique for the detection of
      metastases in bladder cancer patients, especially those with disease that invades
      muscle.

PMID- 22411939
TI  - MR imaging for preoperative evaluation of primary rectal cancer: practical
      considerations.
AB  - High-resolution magnetic resonance (MR) imaging plays a pivotal role in the
      pretreatment assessment of primary rectal cancer. The success of this technique
      depends on obtaining good-quality high-resolution T2-weighted images of the
      primary tumor; the mesorectal fascia, peritoneal reflection, and other pelvic
      viscera; and superior rectal and pelvic sidewall lymph nodes. Although orthogonal
      axial high-resolution T2-weighted MR images are the cornerstone for the staging
      of primary rectal cancer, high-resolution sagittal and coronal images provide
      additional value, particularly in tumors that arise in a redundant tortuous
      rectum. Coronal high-resolution T2-weighted MR images also improve the assessment
      of nodal morphology, particularly for superior rectal and pelvic sidewall nodes,
      and of the relationship between advanced-stage tumors and adjacent pelvic
      structures. Rectal gel should be used in MR imaging examinations conducted for
      the staging of polypoid tumors, previously treated lesions, and small rectal
      tumors. However, it should not be used in examinations performed to stage large
      or low rectal tumors. Diffusion-weighted imaging is useful for identifying nodes
      and, occasionally, the primary tumor when the tumor is difficult to visualize
      with other sequences. Three-dimensional T2-weighted imaging provides multiplanar
      capability with a superior signal-to-noise ratio compared with two-dimensional T2
      weighted imaging.

PMID- 22411940
TI  - Imaging of whole-organ pancreas transplants.
AB  - Whole pancreas transplantation is an established treatment for selected patients
      with diabetic nephropathy or poorly controlled diabetes. Surgical techniques vary
      and have evolved over the past 4 decades. Imaging evaluation of the whole
      pancreas transplant should begin with an understanding of the most commonly used
      surgical techniques and the spectrum of postoperative complications.
      Ultrasonography (US) should be the first-line modality in evaluating the pancreas
      allograft and vasculature. Computed tomography (CT) is useful in the assessment
      of extra-allograft processes, particularly in ruling out abscess formation or
      evaluating suspected bowel complications. Magnetic resonance (MR) imaging is
      reserved for cases in which complete evaluation with US or CT is not possible. MR
      angiography can help provide an accurate assessment of vascular abnormalities.
      The radiologist must be familiar with the spectrum of surgical techniques and the
      normal postoperative imaging appearances of the whole-pancreas transplant so as
      to be able to recognize abnormal postoperative findings. Supplemental material
      available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.322115144/
      /DC1.

PMID- 22411941
TI  - Peritoneal and retroperitoneal anatomy and its relevance for cross-sectional
      imaging.
AB  - It is difficult to identify normal peritoneal folds and ligaments at imaging.
      However, infectious, inflammatory, neoplastic, and traumatic processes frequently
      involve the peritoneal cavity and its reflections; thus, it is important to
      identify the affected peritoneal ligaments and spaces. Knowledge of these
      structures is important for accurate reporting and helps elucidate the sites of
      involvement to the surgeon. The potential peritoneal spaces; the peritoneal
      reflections that form the peritoneal ligaments, mesenteries, and omenta; and the
      natural flow of peritoneal fluid determine the route of spread of intraperitoneal
      fluid and disease processes within the abdominal cavity. The peritoneal
      ligaments, mesenteries, and omenta also serve as boundaries for disease processes
      and as conduits for the spread of disease.

PMID- 22411942
TI  - Identifying, characterizing, and classifying congenital anomalies of the coronary
      arteries.
AB  - The clinical manifestations of coronary artery anomalies vary in severity, with
      some anomalies causing severe symptoms and cardiovascular sequelae and others
      being benign. Cardiovascular computed tomography (CT) has emerged as the standard
      of reference for identification and characterization of coronary artery
      anomalies. Therefore, it is important for the reader of cardiovascular CT images
      to be thoroughly familiar with the spectrum of coronary artery anomalies.
      Hemodynamically significant anomalies include atresia, origin from the pulmonary
      artery, interarterial course, and congenital fistula. Non-hemodynamically
      significant anomalies include duplication; high origin; a prepulmonic,
      transseptal, or retroaortic course; shepherd's crook right coronary artery; and
      systemic termination. In general, coronary arteries with an interarterial course
      are associated with an increased risk of sudden cardiac death. Coronary artery
      anomalies that result in shunting, including congenital fistula and origin from
      the pulmonary artery, are also commonly symptomatic and may cause steal of blood
      from the myocardium. Radiologists should be familiar with each specific variant
      and its specific constellation of potential implications.

PMID- 22411943
TI  - AIRP best cases in radiologic-pathologic correlation: pulmonary sarcoidosis
      complicated by aspergilloma formation.

PMID- 22411944
TI  - CT of blunt diaphragmatic rupture.
AB  - The diagnosis of blunt diaphragmatic rupture (BDR) is difficult and often missed,
      leaving many patients with this traumatic injury at risk for life-threatening
      complications. The potential diagnostic pitfalls are numerous and include
      anatomic variants and congenital and acquired abnormalities. Chest radiography,
      despite its known limitations, may still be helpful in the early assessment of
      severe thoracoabdominal trauma and for detecting initially overlooked BDR or late
      complications of BDR. However, since the development of helical and multidetector
      scanners, computed tomography (CT) has become the reference standard; thus,
      knowledge of the CT signs suggestive of BDR is important for recognition of this
      injury pattern. A large number of CT signs of BDR have been described elsewhere,
      many of them individually, but the use of various appellations for the same sign
      can make previously published reports confusing. The systematic description and
      classification of CT signs provided in this article may help clarify matters and
      provide clues for diagnosing BDR. The authors describe 19 distinct CT signs
      grouped in three categories: direct signs of rupture, indirect signs that are
      consequences of rupture, and signs that are of uncertain origin. Since no single
      CT sign can be considered a marker leading to a correct diagnosis in every case
      of BDR, accurate diagnosis depends on the analysis of all signs present.

PMID- 22411945
TI  - Intracranial lesions with high signal intensity on T1-weighted MR images:
      differential diagnosis.
AB  - Various substances, including methemoglobin, melanin, lipid, protein, calcium,
      iron, copper, and manganese, are responsible for the intrinsically high signal
      intensity observed in intracranial lesions at T1-weighted magnetic resonance (MR)
      imaging. Many of these substances have physical properties that lead to other
      specific imaging features as well. For example, lipid-containing lesions
      frequently produce chemical shift artifact, and some melanin-containing lesions
      exhibit a combination of high signal intensity on T1-weighted images and low
      signal intensity on T2-weighted images. The location and extent of a region of
      abnormal signal hyperintensity may be helpful for identifying rare diseases such
      as an ectopic posterior pituitary gland near the floor of the third ventricle,
      bilateral involvement of the dentate and lentiform nuclei in Cockayne syndrome,
      and involvement of the anterior temporal lobe and cerebellum in neurocutaneous
      melanosis. In cases in which diagnostically specific T1-weighted imaging features
      are lacking, findings obtained with other MR pulse sequences and other modalities
      can help narrow the differential diagnosis: An elevated glutamine or glutamate
      level at MR spectroscopy is suggestive of hepatic encephalopathy; a popcorn ball
      like appearance at T2-weighted imaging, of cavernous malformations; and
      hyperattenuation at computed tomography, of mineral deposition disease. In many
      cases, a comparison of imaging features with clinical measures enables a specific
      diagnosis.

PMID- 22411946
TI  - AIRP best cases in radiologic-pathologic correlation: human coenurosis (Taenia
      Larva).

PMID- 22411947
TI  - Image-guided percutaneous splenic interventions.
AB  - In the spleen, image-guided interventional procedures such as biopsy and catheter
      drainage have not been widely performed because of the perceived increased risk
      of complications. The ability of image-guided biopsy to allow tissue diagnosis of
      a focal splenic mass without the need for splenectomy is the driving force behind
      use of this procedure in oncology patients. The literature on image-guided
      splenic biopsy suggests that the highest biopsy yield is achieved with core
      biopsy and the lowest complication rate is achieved with fine-needle aspiration.
      Image-guided catheter drainage is an effective alternative to splenectomy for
      management of infected splenic collections. In clinical practice, image-guided
      splenic biopsy, fluid aspiration, and catheter drainage have high success rates.
      Image-guided alcohol ablation is effective in treatment of splenic cysts. The
      literature on splenic radiofrequency ablation (RFA) is sparse; therefore, further
      studies are needed to determine the role of RFA in management of splenic
      neoplasms and hypersplenism. Image-guided percutaneous thrombin injection can be
      used to treat splenic artery pseudoaneurysms. Awareness of the correct
      interventional techniques and their limitations is important for safe performance
      of image-guided percutaneous splenic interventions.

PMID- 22411948
TI  - Taking the stress out of evaluating stress injuries in children.
AB  - Pediatric stress injuries result from a mismatch between (a) the burden of
      activity on growing bone and cartilage and (b) their intrinsic biomechanical
      properties. Although the presentation of stress injuries varies with the specific
      physical activity and the site of injury, in children it varies primarily with
      the degree of skeletal maturation. During the past several years, there has been
      a substantial increase in the incidence of pediatric stress injuries. The
      differential diagnosis of a stress injury in a child or adolescent can be
      challenging because the injury sometimes can appear aggressive at imaging
      assessment. Awareness of the spectrum of imaging features of stress injuries can
      help the radiologist to reach the correct diagnosis and prevent unnecessary
      anxiety. This review depicts the range of stress injuries in children and
      adolescents in various anatomic locations, with emphasis on their appearances at
      magnetic resonance imaging.

PMID- 22411949
TI  - Imaging of torticollis in children.
AB  - The normal anatomy of the cervical spine and various imaging techniques for the
      evaluation of torticollis are reviewed, and possible causes of torticollis in
      infants and children are discussed, with an emphasis on relevant imaging
      findings. Torticollis is a congenital or acquired deformity characterized by
      rotational deformity of the cervical spine with secondary tilting of the head.
      Although torticollis is a sign of an underlying disease process, its presence
      does not imply a specific diagnosis, and the cause should be sought if
      torticollis persists or is associated with other symptoms. Congenital
      torticollis, seen in neonates and infants, usually results from craniocervical
      vertebral anomalies or muscular causes, although ocular abnormalities such as
      congenital paralytic squint (strabismus) and congenital nystagmus should also be
      considered. Acquired torticollis, seen in older children and adolescents, is
      often secondary to trauma, infection, or tumors. Imaging should be used as a
      general screening tool only after a complete medical history and clinical
      findings have been obtained. In newborns or infants with congenital torticollis,
      ultrasonography (US) is the modality of choice. In cases of acquired torticollis
      resulting from trauma, conventional radiography (lateral and anteroposterior
      views) should be the first-line imaging modality. In nontraumatic acquired
      torticollis, computed tomography (CT) of the neck or cervical spine is the
      initial imaging study. If CT findings are negative, magnetic resonance (MR)
      imaging of the brain and cervical spine should be performed. The use of multiple
      imaging modalities (conventional radiography, US, CT, and MR imaging) is common
      in the radiologic work-up of torticollis, and radiologists must understand the
      role of each imaging modality in patients of various ages.

PMID- 22411950
TI  - Imaging of the diaphragm: anatomy and function.
AB  - The diaphragm is the primary muscle of ventilation. Dysfunction of the diaphragm
      is an underappreciated cause of respiratory difficulties and may be due to a wide
      variety of entities, including surgery, trauma, tumor, and infection.
      Diaphragmatic disease usually manifests as elevation at chest radiography.
      Functional imaging with fluoroscopy (or ultrasonography or magnetic resonance
      imaging) is a simple and effective method of diagnosing diaphragmatic
      dysfunction, which can be classified as paralysis, weakness, or eventration.
      Diaphragmatic paralysis is indicated by absence of orthograde excursion on quiet
      and deep breathing, with paradoxical motion on sniffing. Diaphragmatic weakness
      is indicated by reduced or delayed orthograde excursion on deep breathing, with
      or without paradoxical motion on sniffing. Eventration is congenital thinning of
      a segment of diaphragmatic muscle and manifests as focal weakness. Treatment of
      diaphragmatic paralysis depends on the cause of the dysfunction and the severity
      of the symptoms. Treatment options include plication and phrenic nerve
      stimulation. Supplemental material available at
      http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.322115127/-/DC1.

PMID- 22411951
TI  - Simplified diagnostic algorithm for Lauge-Hansen classification of ankle
      injuries.
AB  - Ankle injuries occur in a predictable sequence, allowing a logical understanding
      of their classification once the injury mechanism is recognized. The Lauge-Hansen
      classification system was developed on the basis of the mechanism of trauma and
      is useful for guiding treatment. Three radiographic views of the ankle
      (anteroposterior, mortise, and lateral) are necessary to classify an injury with
      the Lauge-Hansen system. Two additional criteria are also necessary: the position
      of the foot at the time of injury and the direction of the deforming force.
      Because understanding the mechanism of trauma is fundamental to classifying the
      injury, three-dimensional movies were assembled for each classification, showing
      the sequence of ligament rupture and bone fractures that occurs with each type of
      traumatic mechanism. Supplemental material available at
      http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.322115017/-/DC1.

PMID- 22411952
TI  - Interactions of abiraterone, eplerenone, and prednisolone with wild-type and
      mutant androgen receptor: a rationale for increasing abiraterone exposure or
      combining with MDV3100.
AB  - Prostate cancer progression can be associated with androgen receptor (AR)
      mutations acquired following treatment with castration and/or an antiandrogen.
      Abiraterone, a rationally designed inhibitor of CYP17A1 recently approved for the
      treatment of docetaxel-treated castration-resistant prostate cancer (CRPC), is
      often effective, but requires coadministration with glucocorticoids to curtail
      side effects. Here, we hypothesized that progressive disease on abiraterone may
      occur secondary to glucocorticoid-induced activation of mutated AR. We found that
      prednisolone plasma levels in patients with CRPC were sufficiently high to
      activate mutant AR. Mineralocorticoid receptor antagonists, such as
      spironolactone and eplerenone that are used to treat side effects related to
      mineralocorticoid excess, can also bind to and activate signaling through wild
      type or mutant AR. Abiraterone inhibited in vitro proliferation and AR-regulated
      gene expression of AR-positive prostate cancer cells, which could be explained by
      AR antagonism in addition to inhibition of steroidogenesis. In fact, activation
      of mutant AR by eplerenone was inhibited by MDV3100, bicalutamide, or greater
      concentrations of abiraterone. Therefore, an increase in abiraterone exposure
      could reverse resistance secondary to activation of AR by residual ligands or
      coadministered drugs. Together, our findings provide a strong rationale for
      clinical evaluation of combined CYP17A1 inhibition and AR antagonism.

PMID- 22411953
TI  - p120RasGAP-mediated activation of c-Src is critical for oncogenic Ras to induce
      tumor invasion.
AB  - Ras genes are the most common targets for somatic gain-of-function mutations in
      human cancers. In this study, we found a high incidence of correlation between
      Ras oncogenic mutations and c-Src activation in human cancer cells. We showed
      that oncogenic Ras induces c-Src activation mainly on the Golgi complex and
      endoplasmic reticulum. Moreover, we identified p120RasGAP as an effector for
      oncogenic Ras to activate c-Src. The recruitment of p120RasGAP to the Golgi
      complex by oncogenic Ras facilitated its interaction with c-Src, thereby leading
      to c-Src activation, and this p120RasGAP-mediated activation of c-Src was
      important for tumor invasion induced by oncogenic Ras. Collectively, our findings
      unveil a relationship between oncogenic Ras, p120RasGAP, and c-Src, suggesting a
      critical role for c-Src in cancers evoked by oncogenic mutations in Ras genes.

PMID- 22411954
TI  - RNAimmuno: a database of the nonspecific immunological effects of RNA
      interference and microRNA reagents.
AB  - The RNAimmuno database was created to provide easy access to information
      regarding the nonspecific effects generated in cells by RNA interference triggers
      and microRNA regulators. Various RNAi and microRNA reagents, which differ in
      length and structure, often cause non-sequence-specific immune responses, in
      addition to triggering the intended sequence-specific effects. The activation of
      the cellular sensors of foreign RNA or DNA may lead to the induction of type I
      interferon and proinflammatory cytokine release. Subsequent changes in the
      cellular transcriptome and proteome may result in adverse effects, including cell
      death during therapeutic treatments or the misinterpretation of experimental
      results in research applications. The manually curated RNAimmuno database gathers
      the majority of the published data regarding the immunological side effects that
      are caused in investigated cell lines, tissues, and model organisms by different
      reagents. The database is accessible at http://rnaimmuno.ibch.poznan.pl and may
      be helpful in the further application and development of RNAi- and microRNA-based
      technologies.

PMID- 22411955
TI  - In vitro reconstitution of yeast splicing with U4 snRNA reveals multiple roles
      for the 3' stem-loop.
AB  - U4 small nuclear RNA (snRNA) plays a fundamental role in the process of
      premessenger RNA splicing, yet many questions remain regarding the location,
      interactions, and roles of its functional domains. To address some of these
      questions, we developed the first in vitro reconstitution system for yeast U4
      small nuclear ribonucleoproteins (snRNPs). We used this system to examine the
      functional domains of U4 by measuring reconstitution of splicing, U4/U6 base
      pairing, and triple-snRNP formation. In contrast to previous work in human
      extracts and Xenopus oocytes, we found that the 3' stem-loop of U4 is necessary
      for efficient base-pairing with U6. In particular, the loop is sensitive to
      changes in both length and sequence. Intriguingly, a number of mutations that we
      tested resulted in more stable interactions with U6 than wild-type U4.
      Nevertheless, each of these mutants was impaired in its ability to support
      splicing, indicating that these regions of U4 have functions subsequent to base
      pair formation with U6. Our data suggest that one such function is likely to be
      in tri-snRNP formation, when U5 joins the U4/U6 di-snRNP. We have identified two
      regions, the upper stem of the 3' stem-loop and the central domain, that promote
      tri-snRNP formation. In addition, the loop of the 3' stem-loop promotes di-snRNP
      formation, while the central domain and the 3'-terminal domain appear to
      antagonize di-snRNP formation.

PMID- 22411956
TI  - ECRG4 is a negative regulator of caspase-8-mediated apoptosis in human T-leukemia
      cells.
AB  - We previously established Fas-resistant variant clones from the human T-cell
      leukemia lines Jurkat and SUP-T13. Comparative gene expression analysis of the
      Fas-resistant and Fas-sensitive clones revealed several genes that were
      aberrantly expressed in the Fas-resistant clones. One of the genes, esophageal
      cancer-related gene 4 (ECRG4), contained a VDAC2-like domain that might be
      associated with apoptotic signals. In the present study, we examined the
      subcellular localization and function of ECRG4 in Fas-mediated apoptosis. By
      confocal fluorescence microscopy, ECRG4-EGFP fusion protein was detected in
      mitochondria, endoplasmic reticulum and the Golgi apparatus in gene-transfected
      HeLa cells. Overexpression of ECRG4 in Fas-sensitive Jurkat cells inhibited
      mitochondrial membrane permeability transition, leading to resistance against Fas
      induced apoptosis. Tumor necrosis factor-alpha-induced apoptosis was also
      suppressed in ECRG4-overexpressing Jurkat cells. Immunoprecipitation assay
      demonstrated that ECRG4 is associated with procaspase-8. The inhibitory mechanism
      included the inhibition of caspase-8 activity and Bid cleavage. Since ECRG4
      expression is downregulated in activated T cells, our results suggest that ECRG4
      is a novel antiapoptotic gene which is involved in the negative regulation of
      caspase-8-mediated apoptosis in T cells.

PMID- 22411957
TI  - Upregulation of HOXA10 in gastric cancer with the intestinal mucin phenotype:
      reduction during tumor progression and favorable prognosis.
AB  - Gastric cancer (GC) is one of the most common malignancies worldwide. Better
      knowledge of the changes in gene expression that occur during gastric
      carcinogenesis may lead to improvements in diagnosis, treatment and prevention.
      In this study, we screened for genes upregulated in GC by comparing gene
      expression profiles from microarray and serial analysis of gene expression and
      identified the HOXA10 gene. The aim of the present study was to investigate the
      significance of HOXA10 in GC. Immunohistochemical analysis demonstrated that 221
      (30%) of 749 GC cases were positive for HOXA10, whereas HOXA10 was scarcely
      expressed in non-neoplastic gastric mucosa except in the case of intestinal
      metaplasia. Next, we analyzed the relationship between HOXA10 expression and
      clinicopathological characteristics. HOXA10 expression showed a significant
      inverse correlation with the depth of invasion and was observed more frequently
      in the differentiated type of GC than in the undifferentiated type of GC. HOXA10
      expression was associated with GC with the intestinal mucin phenotype and
      correlated with CDX2 expression. Furthermore, the prognosis of patients with
      positive HOXA10 expression was significantly better than in the negative
      expression cases. 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide
      and wound healing assay revealed that knockdown of HOXA10 in GC cells by short
      interfering RNA transfection significantly increased viability and motility
      relative to the negative control, indicating that HOXA10 expression inhibits cell
      growth and motility. These results suggest that expression of HOXA10 may be a key
      regulator for GC with the intestinal mucin phenotype.

PMID- 22411958
TI  - The evidence for a role of B cells in multiple sclerosis.
AB  - Understanding the pathogenesis of complex immunologic disorders such as multiple
      sclerosis (MS) is challenging. Abnormalities in many different cell types are
      observed in the immune system and CNS of patients with MS and the identification
      of the primary and secondary events is difficult. Recent studies suggest that the
      model of MS as a disorder mediated only by T cells is overly simplistic and
      propose an important role for B cells in the propagation of the disease. B-cell
      activation in the form of oligoclonal bands (OCB) production is the most
      consistent immunologic finding in patients with MS. Notably, markers of B-cell
      activation within the CSF of patients with MS predict conversion from clinically
      isolated syndrome to clinically definite MS and correlate with MRI activity,
      onset of relapses, and disability progression. In addition, the main genetic risk
      factor in MS is associated with OCB production, and environmental agents
      associated with MS susceptibility (vitamin D and the Epstein-Barr virus)
      influence B-cell proliferation and function. Finally, the only cell-specific
      treatments that are effective in patients with MS are monoclonal antibodies
      targeting the B-cell antigen CD20, suggesting a potentially causative role for B
      cells. Based on current evidence there is no longer doubt that B cells are
      relevant to the etiology and pathogenesis of MS. Elucidating the role of B cells
      in MS will be a fruitful strategy for disease prevention and treatment.

PMID- 22411959
TI  - Hemichorea-hemiballism associated with hyperglycemia and a developmental venous
      anomaly.

PMID- 22411960
TI  - Thrombolysis outcomes in acute ischemic stroke patients with prior stroke and
      diabetes mellitus.

PMID- 22411961
TI  - A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple
      sclerosis.

PMID- 22411962
TI  - Clinical reasoning: A 13-year-old boy presenting with dystonia, myoclonus, and
      anxiety.

PMID- 22411963
TI  - Support legislation to address shortage of chemotherapy drugs.

PMID- 22411964
TI  - Road map for curricular development and professional success: the life cycle of a
      primary care physician.

PMID- 22411965
TI  - Imaging gently: a call for awareness.

PMID- 22411966
TI  - Use of computed tomography in diagnosing appendicitis: redundant, expensive,
      toxic, and potentially unnecessary.
AB  - CONTEXT: Computed tomography is routinely used for the diagnosis of appendicitis
      despite its high cost and its radiation exposure to patients. OBJECTIVE: To
      examine the usefulness and clinical relevance of computed tomography to diagnose
      appendicitis at a community-based academic medical center. METHODS: A
      retrospective review of medical records of patients who received a final
      diagnosis of appendicitis (according to International Classification of Diseases,
      Ninth Revision) from April 26, 2009, to July 27, 2009, was conducted. Emergency
      department and admission history, physical examination reports, ultrasonography
      and computed tomography reports, and operative and pathology reports were
      included in the review. A modified version of the pediatric appendicitis score
      (mPAS) was used to determine the utility of imaging vs physical and laboratory
      examinations. RESULTS: Charts from 36 patients, aged 8 to 22 years, were
      included. All patients had pathologic evidence of appendicitis. Imaging was
      mentioned in 20 of 36 operative reports, but no operative report mentioned
      imaging as a crucial factor in surgical decisions. Two of 5 patients with the
      elevated mPAS of 6 had undergone no imaging; operative decisions were based on
      history, physical examination, and laboratory results. Among the 35 patients who
      had mPAS values, 23 (65.7%) had an mPAS of 5 or greater. The average mPAS for all
      patients was 4.5. Thirty-one of 36 patients (86.1%) had typical physical
      examination indications for appendicitis. CONCLUSION: Computed tomography was
      used as an initial part of the diagnostic workup in most patients, rather than as
      a tool for only atypical cases. A tiered approach-consisting of routine clinical
      evaluation with mPAS, followed by imaging in only atypical cases-would likely
      result in diagnostic accuracy similar to that obtained with early, routine
      imaging. Such an approach would also decrease expense and radiation exposure to
      young, developing bodies.

PMID- 22411967
TI  - Osteopathic manipulative medicine for carpal tunnel syndrome.
AB  - Carpal tunnel syndrome (CTS) is 1 of the most common peripheral nerve entrapment
      disorders. Osteopathic manipulative medicine can be invaluable in diagnosing and
      managing CTS. Combined with a patient's history and a standard physical
      examination, an osteopathic structural examination can facilitate localizing the
      nerve entrapment, diagnosing CTS, and monitoring the disease process. Osteopathic
      manipulative treatment is noninvasive and can be used to supplement traditional
      CTS treatment methods. The authors also review the relevant anatomy involving CTS
      and the clinical efficacy of osteopathic manipulative medicine in the management
      of this disorder.

PMID- 22411968
TI  - Elevated factor VIII: an unfamiliar risk factor for cerebral venous thrombosis.
AB  - An elevated factor VIII level has been shown to be an independent risk factor for
      venous thrombosis. However, physicians screen for this factor far less frequently
      than they screen for other coagulopathies. The causes of increased factor VIII
      levels are likely a combination of genetic and acquired variables. The authors
      describe a case of a healthy 48-year-old woman found to have a cerebral venous
      thrombosis, with her only identifiable risk factor being an elevated factor VIII
      level.

PMID- 22411969
TI  - Unusual case of massive gastrointestinal hemorrhage.

PMID- 22411970
TI  - Occupational and environmental cancer incidence and mortality in China.
AB  - BACKGROUND: Most cancers are due to environmental, occupational or other non
      genetic factors and are potentially preventable. AIMS: To provide an evidence
      based assessment of the burden of occupational and environmental-related cancers
      in China in 2005. METHODS: The population attributable fraction (PAF) was
      calculated based on the assumption of no occupational agent exposure. Relative
      risk estimates for specific cancers of interest and prevalence of exposure were
      mainly derived from large-scale studies. Data on cancer incidence and mortality
      was obtained from the Third National Death Cause Survey and cancer registries in
      China. RESULTS: We estimated that a total of 48,511 deaths of cancer were
      attributable to occupational agents in China in 2005, with 34,975 among men (3.1%
      of all cancer deaths) and 13,536 among women (2.1%). A total of 59,410 incident
      cases of cancer were attributable to occupational agents in China in 2005, with
      42,724 among men (2.8% of all cancer incident cases) and 16,686 among women
      (1.6%). The highest PAF was observed for mesothelioma with asbestos, followed by
      leukaemia, bladder and lung cancers. Indoor radon was responsible for 0.2% of
      lung cancer-related deaths among men and women. CONCLUSIONS: Occupational agents
      represent an important cause of cancer, but indoor radon plays a relatively
      limited role in cancer causes in China. Our report provides strong evidence of
      the need for policy makers to develop strategies to reduce the risk of
      occupational cancers.

PMID- 22411971
TI  - Short-term statin administration in hypercholesterolaemic rabbits resistant to
      postconditioning: effects on infarct size, endothelial nitric oxide synthase, and
      nitro-oxidative stress.
AB  - AIMS: The effectiveness of postconditioning (POC) in hypercholesterolaemia is in
      dispute. We investigated the effects of 3-day lipophilc (simvastatin) or
      hydrophilic (pravastatin) statin treatment, without or with POC in
      normocholesterolaemic (Norm) and hypercholesterolaemic (Chol) rabbits. METHODS
      AND RESULTS: Norm or Chol rabbits were subjected to 30 min ischaemia and
      randomized in two series of 12 groups each: control, simvastatin (Sim),
      pravastatin (Prav), POC, Sim-POC, Prav-POC, Chol, Sim-Chol, Prav-Chol, POC-Chol,
      Sim-POC-Chol, Prav-POC-Chol. After ischaemia, rabbits of the first series
      underwent 3 h reperfusion, followed by infarct size, total cholesterol, and low
      density lipoprotein plasma level evaluation; animals of the second series
      underwent 10 min reperfusion followed by tissue sampling for nitrotyrosine (NT),
      malondialdehyde, endothelial nitric oxide synthase (eNOS), and Akt analyses. N
      nitro-l-arginine methylester (L-NAME) was given in two additional groups (POC-L
      NAME and Prav-Chol-L-NAME) for infarct size assessment. All interventions reduced
      infarction in Norm (24.3 +/- 1.3, 25.9 +/- 2.8, 27.9 +/- 3.1, 23.3 +/- 2.3, and
      33.4 +/- 2.5%, in POC, Sim, Prav, Sim-POC, and Prav-POC groups, respectively, vs.
      49.3 +/- 1.9% in control, P < 0.05), but only Prav did so in Chol animals (25.7
      +/- 3.3 and 25.3 +/- 3.9% in Prav-Chol and Prav-POC-Chol vs. 50.9 +/- 1.7, 44.8
      +/- 4.3, 41.5 +/- 3.5, and 49.3 +/- 5.5% in Chol, Sim-Chol, POC-Chol, and Sim-POC
      Chol, respectively, P < 0.05). L-NAME abolished the infarct size-limiting effect
      of POC and Prav-Chol. Prav induced the greatest reduction in NT, while it was the
      only intervention that increased myocardial eNOS and Akt in Chol rabbits (P <
      0.05 vs. all others). CONCLUSION: Prav, in contrast to same-dose Sim or POC,
      reduces infarction in Chol rabbits independently of lipid lowering, potentially
      through eNOS activation and nitro-oxidative stress attenuation.

PMID- 22411972
TI  - Dietary linoleate preserves cardiolipin and attenuates mitochondrial dysfunction
      in the failing rat heart.
AB  - AIMS: Cardiolipin (CL) is a tetra-acyl phospholipid that provides structural and
      functional support to several proteins in the inner mitochondrial membrane. The
      majority of CL in the healthy mammalian heart contains four linoleic acid acyl
      chains (L(4)CL). A selective loss of L(4)CL is associated with mitochondrial
      dysfunction and heart failure in humans and animal models. We examined whether
      supplementing the diet with linoleic acid would preserve cardiac L(4)CL and
      attenuate mitochondrial dysfunction and contractile failure in rats with
      hypertensive heart failure. METHODS AND RESULTS: Male spontaneously hypertensive
      heart failure rats (21 months of age) were administered diets supplemented with
      high-linoleate safflower oil (HLSO) or lard (10% w/w; 28% kilocalorie fat) or
      without supplemental fat (control) for 4 weeks. HLSO preserved L(4)CL and total
      CL to 90% of non-failing levels (vs. 61-75% in control and lard groups), and
      attenuated 17-22% decreases in state 3 mitochondrial respiration observed in the
      control and lard groups (P < 0.05). Left ventricular fractional shortening was
      significantly higher in HLSO vs. control (33 +/- 2 vs. 29 +/- 2%, P < 0.05),
      while plasma insulin levels were lower (5.4 +/- 1.1 vs. 9.1 +/- 2.3 ng/mL; P <
      0.05), with no significant effect of lard supplementation. HLSO also increased
      serum concentrations of several eicosanoid species compared with control and lard
      diets, but had no effect on plasma glucose or blood pressure. CONCLUSION:
      Moderate consumption of HLSO preserves CL and mitochondrial function in the
      failing heart and may be a useful adjuvant therapy for this condition.

PMID- 22411973
TI  - Ablation of junctin or triadin is associated with increased cardiac injury
      following ischaemia/reperfusion.
AB  - AIMS: Junctin and triadin are calsequestrin-binding proteins that regulate
      sarcoplasmic reticulum (SR) Ca(2+) release by interacting with the ryanodine
      receptor. The levels of these proteins are significantly down-regulated in
      failing human hearts. However, the significance of such decreases is currently
      unknown. Here, we addressed the functional role of these accessory proteins in
      the heart's responses to ischaemia/reperfusion (I/R) injury. METHODS AND RESULTS:
      Isolated mouse hearts were subjected to global I/R, and contractile parameters
      were assessed in wild-type (WT), junctin-knockout (JKO), and triadin-knockout
      (TKO) hearts. Both JKO and TKO were associated with significantly depressed post
      I/R contractile recovery. However, ablation of triadin resulted in the most
      severe post-I/R phenotype. The additional contractile impairment of TKO hearts
      was not related to a mitochondrial death pathway, but attributed to endoplasmic
      reticulum (ER) stress-mediated apoptosis. Activation of the X-box-binding protein
      1 and transcriptional up-regulation of C/EBP-homologous protein (CHOP) provided a
      molecular mechanism of caspase-12-dependent apoptosis in myocytes. In addition,
      elevation of cytosolic Ca(2+) during reperfusion was associated with the
      activation of calpain proteases and troponin I breakdown. Accordingly, treatment
      with the calpain inhibitor MDL-28170 significantly ameliorated post-I/R
      impairment of contractile recovery in intact hearts. CONCLUSION: These findings
      indicate that deficiency of either junctin or triadin impairs the contractile
      recovery in post-ischaemic hearts, which appears to be primarily attributed to
      increased ER stress and activation of calpain.

PMID- 22411974
TI  - Bacterial secretion comes of age.
AB  - Bacterial secretion systems play essential roles in pathogenesis and also in
      maintaining lines of communication between bacterial cells in the bacterial
      microflora or between commensal bacteria and their host. Recent breakthroughs in
      the field have yielded some novel insights into the mechanisms by which these
      systems operate. This issue of Philosophical Transactions B seeks to provide a
      detailed survey of the field, with an emphasis on mechanisms and how their
      unravelling might provide a new future for antibiotics research.

PMID- 22411975
TI  - The bacterial Sec-translocase: structure and mechanism.
AB  - Most bacterial secretory proteins pass across the cytoplasmic membrane via the
      translocase, which consists of a protein-conducting channel SecYEG and an ATP
      dependent motor protein SecA. The ancillary SecDF membrane protein complex
      promotes the final stages of translocation. Recent years have seen a major
      advance in our understanding of the structural and biochemical basis of protein
      translocation, and this has led to a detailed model of the translocation
      mechanism.

PMID- 22411976
TI  - Twin-arginine-dependent translocation of folded proteins.
AB  - Twin-arginine translocation (Tat) denotes a protein transport pathway in
      bacteria, archaea and plant chloroplasts, which is specific for precursor
      proteins harbouring a characteristic twin-arginine pair in their signal
      sequences. Many Tat substrates receive cofactors and fold prior to translocation.
      For a subset of them, proofreading chaperones coordinate maturation and membrane
      targeting. Tat translocases comprise two kinds of membrane proteins, a
      hexahelical TatC-type protein and one or two members of the single-spanning TatA
      protein family, called TatA and TatB. TatC- and TatA-type proteins form homo- and
      hetero-oligomeric complexes. The subunits of TatABC translocases are
      predominantly recovered from two separate complexes, a TatBC complex that might
      contain some TatA, and a homomeric TatA complex. TatB and TatC coordinately
      recognize twin-arginine signal peptides and accommodate them in membrane-embedded
      binding pockets. Advanced binding of the signal sequence to the Tat translocase
      requires the proton-motive force (PMF) across the membranes and might involve a
      first recruitment of TatA. When targeted in this manner, folded twin-arginine
      precursors induce homo-oligomerization of TatB and TatA. Ultimately, this leads
      to the formation of a transmembrane protein conduit that possibly consists of a
      pore-like TatA structure. The translocation step again is dependent on the PMF.

PMID- 22411977
TI  - Structure and mechanism of the tripartite CusCBA heavy-metal efflux complex.
AB  - Gram-negative bacteria frequently expel toxic chemicals through tripartite efflux
      pumps that span both the inner and outer membranes. The three parts are the inner
      membrane, substrate-binding transporter (or pump); a periplasmic membrane fusion
      protein (MFP, or adaptor); and an outer membrane-anchored channel. The fusion
      protein connects the transporter to the channel within the periplasmic space. One
      such efflux system CusCBA is responsible for extruding biocidal Cu(I) and Ag(I)
      ions. We previously described the crystal structures of both the inner membrane
      transporter CusA and the MFP CusB of Escherichia coli. We also determined the co
      crystal structure of the CusBA adaptor-transporter efflux complex, showing that
      the transporter CusA, which is present as a trimer, interacts with six CusB
      protomers and that the periplasmic domain of CusA is involved in these
      interactions. Here, we summarize the structural information of these efflux
      proteins, and present the accumulated evidence that this efflux system uses
      methionine residues to bind and export Cu(I) and Ag(I). Genetic and structural
      analyses suggest that the CusA pump is capable of picking up the metal ions from
      both the periplasm and the cytoplasm. We propose a stepwise shuttle mechanism for
      this pump to export metal ions from the cell.

PMID- 22411979
TI  - Assembly and mechanisms of bacterial type IV secretion machines.
AB  - Type IV secretion occurs across a wide range of prokaryotic cell envelopes: Gram
      negative, Gram-positive, cell wall-less bacteria and some archaea. This diversity
      is reflected in the heterogeneity of components that constitute the secretion
      machines. Macromolecules are secreted in an ATP-dependent process using an
      envelope-spanning multi-protein channel. Similar to the type III systems, this
      apparatus extends beyond the cell surface as a pilus structure important for
      direct contact and penetration of the recipient cell surface. Type IV systems are
      remarkably versatile in that they mobilize a broad range of substrates, including
      single proteins, protein complexes, DNA and nucleoprotein complexes, across the
      cell envelope. These machines have broad clinical significance not only for
      delivering bacterial toxins or effector proteins directly into targeted host
      cells, but also for direct involvement in phenomena such as biofilm formation and
      the rapid horizontal spread of antibiotic resistance genes among the microbial
      community.

PMID- 22411978
TI  - On the path to uncover the bacterial type II secretion system.
AB  - Gram-negative bacteria have evolved several secretory pathways to release enzymes
      or toxins into the surrounding environment or into the target cells. The type II
      secretion system (T2SS) is conserved in Gram-negative bacteria and involves a set
      of 12 to 16 different proteins. Components of the T2SS are located in both the
      inner and outer membranes where they assemble into a supramolecular complex
      spanning the bacterial envelope, also called the secreton. The T2SS substrates
      transiently go through the periplasm before they are translocated across the
      outer membrane and exposed to the extracellular milieu. The T2SS is unique in its
      ability to promote secretion of large and sometimes multimeric proteins that are
      folded in the periplasm. The present review describes recently identified protein
      protein interactions together with structural and functional advances in the
      field that have contributed to improve our understanding on how the type II
      secretion apparatus assembles and on the role played by individual proteins of
      this highly sophisticated system.

PMID- 22411980
TI  - Type V secretion: mechanism(s) of autotransport through the bacterial outer
      membrane.
AB  - Autotransport in Gram-negative bacteria denotes the ability of surface-localized
      proteins to cross the outer membrane (OM) autonomously. Autotransporters perform
      this task with the help of a beta-barrel transmembrane domain localized in the
      OM. Different classes of autotransporters have been investigated in detail in
      recent years; classical monomeric but also trimeric autotransporters comprise
      many important bacterial virulence factors. So do the two-partner secretion
      systems, which are a special case as the transported protein resides on a
      different polypeptide chain than the transporter. Despite the great interest in
      these proteins, the exact mechanism of the transport process remains elusive.
      Moreover, different periplasmic and OM factors have been identified that play a
      role in the translocation, making the term 'autotransport' debatable. In this
      review, we compile the wealth of details known on the mechanism of single
      autotransporters from different classes and organisms, and put them into a bigger
      perspective. We also discuss recently discovered or rediscovered classes of
      autotransporters.

PMID- 22411981
TI  - Structural biology of type VI secretion systems.
AB  - Type VI secretion systems (T6SSs) are transenvelope complexes specialized in the
      transport of proteins or domains directly into target cells. These systems are
      versatile as they can target either eukaryotic host cells and therefore modulate
      the bacteria-host interaction and pathogenesis or bacterial cells and therefore
      facilitate access to a specific niche. These molecular machines comprise at least
      13 proteins. Although recent years have witnessed advances in the role and
      function of these secretion systems, little is known about how these complexes
      assemble in the cell envelope. Interestingly, the current information converges
      to the idea that T6SSs are composed of two subassemblies, one resembling the
      contractile bacteriophage tail, whereas the other subunits are embedded in the
      inner and outer membranes and anchor the bacteriophage-like structure to the cell
      envelope. In this review, we summarize recent structural information on
      individual T6SS components emphasizing the fact that T6SSs are composite systems,
      adapting subunits from various origins.

PMID- 22411982
TI  - Chaperone-usher pathways: diversity and pilus assembly mechanism.
AB  - Up to eight different types of secretion systems, and several more subtypes, have
      been described in Gram-negative bacteria. Here, we focus on the diversity and
      assembly mechanism of one of the best-studied secretion systems, the widespread
      chaperone-usher pathway known to assemble and secrete adhesive surface
      structures, called pili or fimbriae, which play essential roles in targeting
      bacterial pathogens to the host.

PMID- 22411984
TI  - The blueprint of the type-3 injectisome.
AB  - Type-3 secretion systems are sophisticated syringe-like nanomachines present in
      many animal and plant Gram-negative pathogens. They are capable of translocating
      an arsenal of specific bacterial toxins (effector proteins) from the prokaryotic
      cytoplasm across the three biological membranes directly into the eukaryotic
      cytosol, some of which modulate host cell mechanisms for the benefit of the
      pathogen. They populate a particular biological niche, which is maintained by
      specific, pathogen-dependent effectors. In contrast, the needle complex, which is
      the central component of this specialized protein delivery machine, is
      structurally well-conserved. It is a large supramolecular cylindrical structure
      composed of multiple copies of a relatively small subset of proteins, is embedded
      in the bacterial membranes and protrudes from the pathogen's surface with a
      needle filament. A central channel traverses the entire needle complex, and
      serves as a hollow conduit for proteins destined to travel this secretion
      pathway. In the past few years, there has been a tremendous increase in an
      understanding on both the structural and the mechanistic level. This review will
      thus focus on new insights of this remarkable molecular machine.

PMID- 22411983
TI  - Protein secretion and surface display in Gram-positive bacteria.
AB  - The cell wall peptidoglycan of Gram-positive bacteria functions as a surface
      organelle for the transport and assembly of proteins that interact with the
      environment, in particular, the tissues of an infected host. Signal peptide
      bearing precursor proteins are secreted across the plasma membrane of Gram
      positive bacteria. Some precursors carry C-terminal sorting signals with unique
      sequence motifs that are cleaved by sortase enzymes and linked to the cell wall
      peptidoglycan of vegetative forms or spores. The sorting signals of pilin
      precursors are cleaved by pilus-specific sortases, which generate covalent bonds
      between proteins leading to the assembly of fimbrial structures. Other precursors
      harbour surface (S)-layer homology domains (SLH), which fold into a three-pronged
      spindle structure and bind secondary cell wall polysaccharides, thereby
      associating with the surface of specific Gram-positive microbes. Type VII
      secretion is a non-canonical secretion pathway for WXG100 family proteins in
      mycobacteria. Gram-positive bacteria also secrete WXG100 proteins and carry
      unique genes that either contribute to discrete steps in secretion or represent
      distinctive substrates for protein transport reactions.

PMID- 22411985
TI  - Novel role for proteinase-activated receptor 2 (PAR2) in membrane trafficking of
      proteinase-activated receptor 4 (PAR4).
AB  - Proteinase-activated receptors 4 (PAR(4)) is a class A G protein-coupled receptor
      (GPCR) recognized through the ability of serine proteases such as thrombin and
      trypsin to mediate receptor activation. Due to the irreversible nature of
      activation, a fresh supply of receptor is required to be mobilized to the cell
      surface for responsiveness to agonist to be sustained. Unlike other PAR subtypes,
      the mechanisms regulating receptor trafficking of PAR(4) remain unknown. Here, we
      report novel features of the intracellular trafficking of PAR(4) to the plasma
      membrane. PAR(4) was poorly expressed at the plasma membrane and largely retained
      in the endoplasmic reticulum (ER) in a complex with the COPI protein subunit beta
      COP1. Analysis of the PAR(4) protein sequence identified an arginine-based (RXR)
      ER retention sequence located within intracellular loop-2 (R(183)AR -> A(183)AA),
      mutation of which allowed efficient membrane delivery of PAR(4). Interestingly,
      co-expression with PAR(2) facilitated plasma membrane delivery of PAR(4), an
      effect produced through disruption of beta-COP1 binding and facilitation of
      interaction with the chaperone protein 14-3-3zeta. Intermolecular FRET studies
      confirmed heterodimerization between PAR(2) and PAR(4). PAR(2) also enhanced
      glycosylation of PAR(4) and activation of PAR(4) signaling. Our results identify
      a novel regulatory role for PAR(2) in the anterograde traffic of PAR(4). PAR(2)
      was shown to both facilitate and abrogate protein interactions with PAR(4),
      impacting upon receptor localization and cell signal transduction. This work is
      likely to impact markedly upon the understanding of the receptor pharmacology of
      PAR(4) in normal physiology and disease.

PMID- 22411986
TI  - Yap1 protein regulates vascular smooth muscle cell phenotypic switch by
      interaction with myocardin.
AB  - The Hippo-Yap (Yes-associated protein) signaling pathway has emerged as one of
      the critical pathways regulating cell proliferation, differentiation, and
      apoptosis in response to environmental and developmental cues. However, Yap1
      roles in vascular smooth muscle cell (VSMC) biology have not been investigated.
      VSMCs undergo phenotypic switch, a process characterized by decreased gene
      expression of VSMC contractile markers and increased proliferation, migration,
      and matrix synthesis. The goals of the present studies were to investigate the
      relationship between Yap1 and VSMC phenotypic switch and to determine the
      molecular mechanisms by which Yap1 affects this essential process in VSMC
      biology. Results demonstrated that the expression of Yap1 was rapidly up
      regulated by stimulation with PDGF-BB (a known inducer of phenotypic switch in
      VSMCs) and in the injured vessel wall. Knockdown of Yap1 impaired VSMC
      proliferation in vitro and enhanced the expression of VSMC contractile genes as
      well by increasing serum response factor binding to CArG-containing regions of
      VSMC-specific contractile genes within intact chromatin. Conversely, the
      interaction between serum response factor and its co-activator myocardin was
      reduced by overexpression of Yap1 in a dose-dependent manner. Taken together,
      these results indicate that down-regulation of Yap1 promotes VSMC contractile
      phenotype by both up-regulating myocardin expression and promoting the
      association of the serum response factor-myocardin complex with VSMC contractile
      gene promoters and suggest that the Yap1 signaling pathway is a central regulator
      of phenotypic switch of VSMCs.

PMID- 22411987
TI  - The gap junction channel protein connexin 43 is covalently modified and regulated
      by SUMOylation.
AB  - SUMOylation is a posttranslational modification in which a member of the small
      ubiquitin-like modifier (SUMO) family of proteins is conjugated to lysine
      residues in specific target proteins. Most known SUMOylation target proteins are
      located in the nucleus, but there is increasing evidence that SUMO may also be a
      key determinant of many extranuclear processes. Gap junctions consist of arrays
      of intercellular channels that provide direct transfer of ions and small
      molecules between adjacent cells. Gap junction channels are formed by integral
      membrane proteins called connexins, of which the best-studied isoform is connexin
      43 (Cx43). Here we show that Cx43 is posttranslationally modified by SUMOylation.
      The data suggest that the SUMO system regulates the Cx43 protein level and the
      level of functional Cx43 gap junctions at the plasma membrane. Cx43 was found to
      be modified by SUMO-1, -2, and -3. Evidence is provided that the membrane
      proximal lysines at positions 144 and 237, located in the Cx43 intracellular loop
      and C-terminal tail, respectively, act as SUMO conjugation sites. Mutations of
      lysine 144 or lysine 237 resulted in reduced Cx43 SUMOylation and reduced Cx43
      protein and gap junction levels. Altogether, these data identify Cx43 as a
      SUMOylation target protein and represent the first evidence that gap junctions
      are regulated by the SUMO system.

PMID- 22411988
TI  - Mechanism for CARMIL protein inhibition of heterodimeric actin-capping protein.
AB  - Capping protein (CP) controls the polymerization of actin filaments by capping
      their barbed ends. In lamellipodia, CP dissociates from the actin cytoskeleton
      rapidly, suggesting the possible existence of an uncapping factor, for which the
      protein CARMIL (capping protein, Arp2/3 and myosin-I linker) is a candidate.
      CARMIL binds to CP via two motifs. One, the CP interaction (CPI) motif, is found
      in a number of unrelated proteins; the other motif is unique to CARMILs, the
      CARMIL-specific interaction motif. A 115-aa CARMIL fragment of CARMIL with both
      motifs, termed the CP-binding region (CBR), binds to CP with high affinity,
      inhibits capping, and causes uncapping. We wanted to understand the structural
      basis for this function. We used a collection of mutants affecting the actin
      binding surface of CP to test the possibility of a steric-blocking model, which
      remained open because a region of CBR was not resolved in the CBR/CP co-crystal
      structure. The CP actin-binding mutants bound CBR normally. In addition, a CBR
      mutant with all residues of the unresolved region changed showed nearly normal
      binding to CP. Having ruled out a steric blocking model, we tested an allosteric
      model with molecular dynamics. We found that CBR binding induces changes in the
      conformation of the actin-binding surface of CP. In addition, ~30-aa truncations
      on the actin-binding surface of CP decreased the affinity of CBR for CP. Thus,
      CARMIL promotes uncapping by binding to a freely accessible site on CP bound to a
      filament barbed end and inducing a change in the conformation of the actin
      binding surface of CP.

PMID- 22411989
TI  - Mononuclear iron enzymes are primary targets of hydrogen peroxide stress.
AB  - This study tested whether nonredox metalloenzymes are commonly charged with iron
      in vivo and are primary targets of oxidative stress because of it. Indeed, three
      sample mononuclear enzymes, peptide deformylase, threonine dehydrogenase, and
      cytosine deaminase, were rapidly damaged by micromolar hydrogen peroxide in vitro
      and in live Escherichia coli. The first two enzymes use a cysteine residue to
      coordinate the catalytic metal atom; it was quantitatively oxidized by the
      radical generated by the Fenton reaction. Because oxidized cysteine can be
      repaired by cellular reductants, the effect was to avoid irreversible damage to
      other active-site residues. Nevertheless, protracted H(2)O(2) exposure gradually
      inactivated these enzymes, consistent with the overoxidation of the cysteine
      residue to sulfinic or sulfonic forms. During H(2)O(2) stress, E. coli defended
      all three proteins by inducing MntH, a manganese importer, and Dps, an iron
      sequestration protein. These proteins appeared to collaborate in replacing the
      iron atom with nonoxidizable manganese. The implication is that mononuclear
      metalloproteins are common targets of H(2)O(2) and that both structural and
      metabolic arrangements exist to protect them.

PMID- 22411990
TI  - Sorting nexin 27 interacts with multidrug resistance-associated protein 4 (MRP4)
      and mediates internalization of MRP4.
AB  - Multidrug resistance-associated protein 4 (MRP4/ABCC4) makes a vital contribution
      to the bodily distribution of drugs and endogenous compounds because of its
      cellular efflux abilities. However, little is known about the mechanism
      regulating its cell surface expression. MRP4 has a PDZ-binding motif, which is a
      potential sequence that modulates the membrane expression of MRP4 via interaction
      with PDZ adaptor proteins. To investigate this possible relationship, we
      performed GST pull-down assays and subsequent analysis with matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry. This method identified
      sorting nexin 27 (SNX27) as the interacting PDZ adaptor protein with a PDZ
      binding motif of MRP4. Its interaction was confirmed by a coimmunoprecipitation
      study using HEK293 cells. Knockdown of SNX27 by siRNA in HEK293 cells raised MRP4
      expression on the plasma membrane, increased the extrusion of 6
      [(14)C]mercaptopurine, an MRP4 substrate, and conferred resistance against 6
      [(14)C]mercaptopurine. Cell surface biotinylation studies indicated that the
      inhibition of MRP4 internalization was responsible for these results.
      Immunocytochemistry and cell surface biotinylation studies using COS-1 cells
      showed that SNX27 localized to both the early endosome and the plasma membrane.
      These data suggest that SNX27 interacts with MRP4 near the plasma membrane and
      promotes endocytosis of MRP4 and thereby negatively regulates its cell surface
      expression and transport function.

PMID- 22411992
TI  - Exploring light and life.

PMID- 22411991
TI  - Overexpression of SKI oncoprotein leads to p53 degradation through regulation of
      MDM2 protein sumoylation.
AB  - Protooncogene Ski was identified based on its ability to transform avian
      fibroblasts in vitro. In support of its oncogenic activity, SKI was found to be
      overexpressed in a variety of human cancers, although the exact molecular
      mechanism(s) responsible for its oncogenic activity is not fully understood. We
      found that SKI can negatively regulate p53 by decreasing its level through up
      regulation of MDM2 activity, which is mediated by the ability of SKI to enhance
      sumoylation of MDM2. This stimulation of MDM2 sumoylation is accomplished through
      a direct interaction of SKI with SUMO-conjugating enzyme E2, Ubc9, resulting in
      enhanced thioester bond formation and mono-sumoylation of Ubc9. A mutant SKI
      defective in transformation fails to increase p53 ubiquitination and is unable to
      increase MDM2 levels and to increase mono-sumoylation of Ubc9, suggesting that
      the ability of SKI to enhance Ubc9 activity is essential for its transforming
      function. These results established a detailed molecular mechanism that underlies
      the ability of SKI to cause cellular transformation while unraveling a novel
      connection between sumoylation and tumorigenesis, providing potential new
      therapeutic targets for cancer.

PMID- 22411993
TI  - Sequences flanking Arg336 in factor VIIIa modulate factor Xa-catalyzed cleavage
      rates at this site and cofactor function.
AB  - Factor (F)VIII can be activated to FVIIIa by FXa following cleavages at Arg(372),
      Arg(740), and Arg(1689). FXa also cleaves FVIII/FVIIIa at Arg(336) and Arg(562)
      resulting in inactivation of the cofactor. These inactivating cleavages occur on
      a slower time scale than the activating ones. We assessed the contributions to
      cleavage rate and cofactor function of residues flanking Arg(336), the primary
      site yielding FVIII(a) inactivation, following replacement of these residues with
      those flanking the faster-reacting Arg(740) and Arg(372) sites and the slower
      reacting Arg(562) site. Replacing P4-P3' residues flanking Arg(336) with those
      from Arg(372) or Arg(740) resulted in ~4-6-fold increases in rates of FXa
      catalyzed inactivation of FVIIIa, which paralleled the rates of proteolysis at
      Arg(336). Examination of partial sequence replacements showed a predominant
      contribution of prime residues flanking the scissile bonds to the enhanced rates.
      Conversely, replacement of this sequence with residues flanking the slow-reacting
      Arg(562) site yielded inactivation and cleavage rates that were ~40% that of the
      WT values. The capacity for FXa to activate FVIII variants where cleavage at
      Arg(336) was accelerated due to flanking sequence replacement showed marked
      reductions in peak activity, whereas reducing the cleavage rate at this site
      enhanced peak activity. Furthermore, plasma-based thrombin generation assays
      employing the variants revealed significant reductions in multiple parameter
      values with acceleration of Arg(336) cleavage suggesting increased down
      regulation of FXase. Overall, these results are consistent with a model of
      competition for activating and inactivating cleavages catalyzed by FXa that is
      modulated in large part by sequences flanking the scissile bonds.

PMID- 22411994
TI  - Tri-domain bifunctional inhibitor of metallocarboxypeptidases A and serine
      proteases isolated from marine annelid Sabellastarte magnifica.
AB  - This study describes a novel bifunctional metallocarboxypeptidase and serine
      protease inhibitor (SmCI) isolated from the tentacle crown of the annelid
      Sabellastarte magnifica. SmCI is a 165-residue glycoprotein with a molecular mass
      of 19.69 kDa (mass spectrometry) and 18 cysteine residues forming nine disulfide
      bonds. Its cDNA was cloned and sequenced by RT-PCR and nested PCR using
      degenerated oligonucleotides. Employing this information along with data derived
      from automatic Edman degradation of peptide fragments, the SmCI sequence was
      fully characterized, indicating the presence of three bovine pancreatic trypsin
      inhibitor/Kunitz domains and its high homology with other Kunitz serine protease
      inhibitors. Enzyme kinetics and structural analyses revealed SmCI to be an
      inhibitor of human and bovine pancreatic metallocarboxypeptidases of the A-type
      (but not B-type), with nanomolar K(i) values. SmCI is also capable of inhibiting
      bovine pancreatic trypsin, chymotrypsin, and porcine pancreatic elastase in
      varying measures. When the inhibitor and its nonglycosylated form (SmCI N23A
      mutant) were overproduced recombinantly in a Pichia pastoris system, they
      displayed the dual inhibitory properties of the natural form. Similarly, two bi
      domain forms of the inhibitor (recombinant rSmCI D1-D2 and rSmCI D2-D3) as well
      as its C-terminal domain (rSmCI-D3) were also overproduced. Of these fragments,
      only the rSmCI D1-D2 bi-domain retained inhibition of metallocarboxypeptidase A
      but only partially, indicating that the whole tri-domain structure is required
      for such capability in full. SmCI is the first proteinaceous inhibitor of
      metallocarboxypeptidases able to act as well on another mechanistic class of
      proteases (serine-type) and is the first of this kind identified in nature.

PMID- 22411995
TI  - Structure of a yeast Dyn2-Nup159 complex and molecular basis for dynein light
      chain-nuclear pore interaction.
AB  - The nuclear pore complex gates nucleocytoplasmic transport through a massive,
      eight-fold symmetric channel capped by a nucleoplasmic basket and structurally
      unique, cytoplasmic fibrils whose tentacles bind and regulate asymmetric traffic.
      The conserved Nup82 complex, composed of Nsp1, Nup82, and Nup159, forms the
      unique cytoplasmic fibrils that regulate mRNA nuclear export. Although the
      nuclear pore complex plays a fundamental, conserved role in nuclear trafficking,
      structural information about the cytoplasmic fibrils is limited. Here, we
      investigate the structural and biochemical interactions between Saccharomyces
      cerevisiae Nup159 and the nucleoporin, Dyn2. We find that Dyn2 is predominantly a
      homodimer and binds arrayed sites on Nup159, promoting the Nup159 parallel
      homodimerization. We present the first structure of Dyn2, determined at 1.85 A
      resolution, complexed with a Nup159 target peptide. Dyn2 resembles homologous
      metazoan dynein light chains, forming homodimeric composite substrate binding
      sites that engage two independent 10-residue target motifs, imparting a beta
      strand structure to each peptide via antiparallel extension of the Dyn2 core beta
      sandwich. Dyn2 recognizes a highly conserved QT motif while allowing sequence
      plasticity in the flanking residues of the peptide. Isothermal titration
      calorimetric analysis of the comparative binding of Dyn2 to two Nup159 target
      sites shows similar affinities (18 and 13 MUM), but divergent thermal binding
      modes. Dyn2 homodimers are arrayed in the crystal lattice, likely mimicking the
      arrayed architecture of Dyn2 on the Nup159 multivalent binding sites.
      Crystallographic interdimer interactions potentially reflect a cooperative basis
      for Dyn2-Nup159 complex formation. Our data highlight the determinants that
      mediate oligomerization of the Nup82 complex and promote a directed, elongated
      cytoplasmic fibril architecture.

PMID- 22411996
TI  - Inhibition of colony-spreading activity of Staphylococcus aureus by secretion of
      delta-hemolysin.
AB  - Staphylococcus aureus spreads on the surface of soft agar, a phenomenon we termed
      "colony spreading." Here, we found that S. aureus culture supernatant inhibited
      colony spreading. We purified delta-hemolysin (Hld, delta-toxin), a major protein
      secreted from S. aureus, as a compound that inhibits colony spreading. The
      culture supernatants of hld-disrupted mutants had 30-fold lower colony-spreading
      inhibitory activity than those of the parent strain. Furthermore, hld-disrupted
      mutants had higher colony-spreading ability than the parent strain. These results
      suggest that S. aureus negatively regulates colony spreading by secreting delta
      hemolysin.

PMID- 22411997
TI  - Effect of prothrombotic mutations on factor consumption in children with
      hemophilia.
AB  - INTRODUCTION: In hemophilia A, factor activity usually correlates with clinical
      severity; however, there are patients with severe hemophilia who have bleeding
      less than expected. AIM: The aim of this study is to evaluate the impact of
      prothrombotic mutations on annual factor consumption in children with hemophilia.
      METHODS: Factor V Leiden (FVL) G1691A, Prothrombin (PT) G20210A and
      methylenetetrahydrofolate reductase (MTHFR) C677T and A128C mutations were
      evaluated in children with moderate-severe hemophilia A (n = 51) and controls (n
      = 25). RESULTS: None of the cases and controls carried the FVL and PT G20210A in
      homozygous state. There was no difference in factor consumption between carriers
      of FVL, PT mutations, and noncarriers. Patients who were homozygous for MTHFR
      C677T were found to have increased factor consumption compared to noncarriers,
      and this was a negative association. No decrease in factor consumption was noted
      in patients with hemophilia having MTHFR A1298C mutation. CONCLUSION: We could
      not demonstrate a significant decrease in factor concentrate consumption in
      children with hemophilia having prothrombotic mutations.

PMID- 22411998
TI  - Considerations on a tentative classification of FVII deficiency suited for
      practical clinical purposes.
AB  - Adequate classifications of disorders are of paramount importance in the
      management of congenital bleeding disorders. Classification of congenital FVII
      deficiency should be simple, based on few tests using thromboplastins of
      different origin. The first thromboplastin to be used is a rabbit brain
      preparation since it has been proven that this is the one that, overall, yields
      the lowest activity level. This is particularly so since molecular biology
      techniques have supplied important information with regard to the structure
      function relation but have failed to supply a satisfactory classification of the
      defect. Mutations in the same domain have yielded different forms of FVII
      deficiency. Furthermore, molecular biology techniques are time consuming and are
      not feasible in every laboratory. A classification of FVII deficiency based on
      clinical, clotting, and immunological assays is proposed. This classification is
      suited for practical clinical purposes and may represent a useful preparatory
      basis for molecular biology studies.

PMID- 22411999
TI  - Use of conjugated estrogens in life-threatening gastrointestinal bleeding in
      hemodialysis patients--a review.
AB  - Hormonal agents (estrogen and progesterone) are being studied for their use in
      bleeding. This observance was initially explored in a patient with hereditary
      hemorrhagic telangiectasia (HHT) with epistaxis had variation in bleeding
      depending on her menstrual cycles.(1) Thus, hormonal therapy was initially used
      in patients with HHT to control episodes of epistaxis.(2) The literature on
      hormonal therapy in patients with life-threatening bleeding from gastrointestinal
      (GI) lesions is very limited. There are a few clinical trials in patients with
      chronic bleeds. However, no definite guidelines exist on their use in life
      threatening GI bleeding in patients with uremia. Here, we describe a case with a
      life-threatening GI bleeding requiring multiple endoscopies and intensive care
      unit stay that responded to conjugated estrogens. We have done extensive research
      on English medical literature on PubMed and Google Scholar on the use of hormonal
      therapy for GI bleeding in patients with renal failure, and here we present the
      data as a review.

PMID- 22412000
TI  - Toward a more cogent approach to the challenges of multimorbidity.

PMID- 22412001
TI  - Lung cancer screening practices of primary care physicians: results from a
      national survey.
AB  - PURPOSE: Although current practice guidelines do not recommend screening
      asymptomatic patients for lung cancer, physicians may still order lung cancer
      screening tests. No recent national survey of health care professionals has
      focused on lung cancer screening. In this study, we examined the lung cancer
      screening practices of US primary care physicians and characteristics of those
      who order lung cancer screening tests. METHODS: We conducted a nationally
      representative survey of practicing primary care physicians in 2006-2007. Mailed
      questionnaires assessed the physicians' knowledge of lung cancer screening
      guidelines, beliefs about the effectiveness of screening tests, and ordering of
      screening chest radiograph, low-dose spiral computed tomography, or sputum
      cytology in the past 12 months. Clinical vignettes were used to assess the
      physicians' intentions to screen asymptomatic 50-year-old patients with varying
      smoking histories for lung cancer. RESULTS: A total of 962 family physicians,
      general practitioners, and general internists completed questionnaires
      (cooperation rate = 76.8%). Overall, 38% had ordered no lung cancer screening
      tests; 55% had ordered chest radiograph, 22% low-dose spiral computed tomography,
      and less than 5% sputum cytology. In multivariate modeling, physicians were more
      likely to have ordered lung cancer screening tests if they believed that expert
      groups recommend lung cancer screening or that screening tests are effective; if
      they would recommend screening for asymptomatic patients, including patients
      without substantial smoking exposure; and if their patients had asked them about
      screening. CONCLUSIONS: Primary care physicians in the United States frequently
      order lung cancer screening tests for asymptomatic patients, even though expert
      groups do not recommend it. Primary care physicians and patients need more
      information about lung cancer screening's evidence base, guidelines, potential
      harms, and costs to avert inappropriate ordering.

PMID- 22412002
TI  - How the medical culture contributes to coworker-perpetrated harassment and abuse
      of family physicians.
AB  - PURPOSE: Harassment and abuse in the workplace of family physicians has been
      associated with higher levels of stress, increased consumption of alcohol, and
      higher risk for developing mental health problems. Few studies have examined
      issues contributing to abusive encounters in the workplace of family physicians.
      METHODS: For the overall study we used a mixed methods design, which included a
      cross-sectional survey of a randomly selected sample of active family physicians
      from the database of the College of Family Physicians of Canada and telephone
      interviews with those who reported experiencing work related harassment and abuse
      in the last year. The data presented here arise from the qualitative interviews
      of the study, which were analyzed thematically. RESULTS: The interview arm of the
      study included 23 female and 14 male participants. The major themes that emerged
      from the study were (1) modeling of abusive behaviors, (2) status hierarchy among
      various medical disciplines, (3) shortage of physicians, and (4) lack of
      transparent policies and follow-up procedures after abusive encounters. The
      results are discussed using the broken window theory. CONCLUSION: Many family
      physicians experience harassing and abusive encounters during their training or
      in the workplace. The current medical culture appears to contribute to harassment
      and abuse in the workplace of family physicians in Canada. We described the
      components that intentionally or unintentionally facilitate abusive behavior in
      the medical culture.

PMID- 22412003
TI  - Video elicitation interviews: a qualitative research method for investigating
      physician-patient interactions.
AB  - We describe the concept and method of video elicitation interviews and provide
      practical guidance for primary care researchers who want to use this qualitative
      method to investigate physician-patient interactions. During video elicitation
      interviews, researchers interview patients or physicians about a recent clinical
      interaction using a video recording of that interaction as an elicitation tool.
      Video elicitation is useful because it allows researchers to integrate data about
      the content of physician-patient interactions gained from video recordings with
      data about participants' associated thoughts, beliefs, and emotions gained from
      elicitation interviews. This method also facilitates investigation of specific
      events or moments during interactions. Video elicitation interviews are
      logistically demanding and time consuming, and they should be reserved for
      research questions that cannot be fully addressed using either standard
      interviews or video recordings in isolation. As many components of primary care
      fall into this category, high-quality video elicitation interviews can be an
      important method for understanding and improving physician-patient interactions
      in primary care.

PMID- 22412004
TI  - Association of patient-centered outcomes with patient-reported and ICD-9-based
      morbidity measures.
AB  - PURPOSE: Evaluating patient-centered care for complex patients requires morbidity
      measurement appropriate for use with a variety of clinical outcomes. We compared
      the contributions of self-reported morbidity and morbidity measured using
      administrative diagnosis data for both patient-reported outcomes and utilization
      outcomes. METHODS: Using a cohort of 961 persons aged 65 years or older with 3 or
      more medical conditions, we explored 9 health outcomes as a function of 4
      independent variables representing different types of morbidity measures:
      International Classification of Diseases, Ninth Revision (ICD-9), a self-reported
      weighted count of conditions, and self-reported symptoms of depression and of
      anxiety. Outcomes varied from self-reported health status to utilization.
      Depending on the outcome measure, we used multivariate linear, negative binomial,
      or logistic regression, adjusting for demographic characteristics and length of
      enrollment to assess associations between dependent and all 4 independent
      variables. RESULTS: Higher morbidity measured by ICD-9 diagnoses was
      independently associated with less favorable levels of 7 of the 9 clinical
      outcomes. Higher self-reported disease burden was significantly associated with
      less favorable levels of 8 of the outcomes, controlling for the 3 other morbidity
      measures. Morbidity measured by diagnosis code was more strongly associated with
      higher utilization, whereas self-reported disease burden and emotional symptoms
      were more strongly associated with patient-reported outcomes. CONCLUSIONS: A
      comprehensive assessment of morbidity requires both subjective and objective
      measurement of disease burden as well as an assessment of emotional symptoms.
      Such multidimensional morbidity measurement is particularly relevant for research
      or quality assessments involving the delivery of patient-centered care to complex
      patient populations.

PMID- 22412005
TI  - Measures of multimorbidity and morbidity burden for use in primary care and
      community settings: a systematic review and guide.
AB  - PURPOSE: Many patients consulting in primary care have multiple conditions
      (multimorbidity). Aims of this review were to identify measures of multimorbidity
      and morbidity burden suitable for use in research in primary care and community
      populations, and to investigate their validity in relation to anticipated
      associations with patient characteristics, process measures, and health outcomes.
      METHODS: Studies were identified using searches in MEDLINE and EMBASE from
      inception to December 2009 and bibliographies. RESULTS: Included were 194
      articles describing 17 different measures. Commonly used measures included
      disease counts (n = 98), Chronic Disease Score (CDS)/RxRisk (n = 17), Adjusted
      Clinical Groups (ACG) System (n = 25), the Charlson index (n = 38), the
      Cumulative Index Illness Rating Scale (CIRS; n = 10) and the Duke Severity of
      Illness Checklist (DUSOI; n = 6). Studies that compared measures suggest their
      predictive validity for the same outcome differs only slightly. Evidence is
      strongest for the ACG System, Charlson index, or disease counts in relation to
      care utilization; for the ACG System in relation to costs; for Charlson index in
      relation to mortality; and for disease counts or Charlson index in relation to
      quality of life. Simple counts of diseases or medications perform almost as well
      as complex measures in predicting most outcomes. Combining measures can improve
      validity. CONCLUSIONS: The measures most commonly used in primary care and
      community settings are disease counts, Charlson index, ACG System, CIRS, CDS, and
      DUSOI. Different measures are most appropriate according to the outcome of
      interest. Choice of measure will also depend on the type of data available. More
      research is needed to directly compare performance of different measures.

PMID- 22412007
TI  - New pathways for primary care: an update on primary care programs from the
      innovation center at CMS.
AB  - Those in practice find that the fee-for-service system does not adequately value
      the contributions made by primary care. The Center for Medicare and Medicaid
      Innovation (Innovation Center) was created by the Affordable Care Act to test new
      models of health care delivery to improve the quality of care while lowering
      costs. All programs coming out of the Innovation Center are tests of new payment
      and service delivery models. By changing both payment and delivery models and
      moving to a payment model that rewards physicians for quality of care instead of
      volume of care, we may be able to achieve the kind of health care patients want
      to receive and primary care physicians want to provide.

PMID- 22412006
TI  - A systematic review of prevalence studies on multimorbidity: toward a more
      uniform methodology.
AB  - PURPOSE: We sought to identify and compare studies reporting the prevalence of
      multimorbidity and to suggest methodologic aspects to be considered in the
      conduct of such studies. METHODS: We searched the literature for English- and
      French-language articles published between 1980 and September 2010 that described
      the prevalence of multimorbidity in the general population, in primary care, or
      both. We assessed quality of included studies with a modified version of the
      Strengthening the Reporting of Observational Studies in Epidemiology checklist.
      Results of individual prevalence studies were adjusted so that they could be
      compared graphically. RESULTS: The final sample included 21 articles: 8 described
      studies conducted in primary care, 12 in the general population, and 1 in both.
      All articles were of good quality. The largest differences in prevalence of
      multimorbidity were observed at age 75 in both primary care (with prevalence
      ranging from 3.5% to 98.5% across studies) and the general population (with
      prevalence ranging from 13.1% to 71.8% across studies). Apart from differences in
      geographic settings, we identified differences in recruitment method and sample
      size (primary care: 980-60,857 patients; general population: 1,099-316,928
      individuals), data collection, and the operational definition of multimorbidity
      used, including the number of diagnoses considered (primary care: 5 to all;
      general population: 7 to all). This last aspect seemed to be the most important
      factor in estimating prevalence. CONCLUSIONS: Marked variation exists among
      studies of the prevalence of multimorbidity with respect to both methodology and
      findings. When undertaking such studies, investigators should carefully consider
      the specific diagnoses included and their number, as well as the operational
      definition of multimorbidity.

PMID- 22412008
TI  - Who will have health insurance in the future? An updated projection.
AB  - The passage of the 2010 Patient Protection and Affordable Care Act (PPACA) in the
      United States put the issues of health care reform and health care costs back in
      the national spotlight. DeVoe and colleagues previously estimated that the cost
      of a family health insurance premium would equal the median household income by
      the year 2025. A slowdown in health care spending tied to the recent economic
      downturn and the passage of the PPACA occurred after this model was published. In
      this updated model, we estimate that this threshold will be crossed in 2033, and
      under favorable assumptions the PPACA may extend this date only to 2037.
      Continuing to make incremental changes in US health policy will likely not bend
      the cost curve, which has eluded policy makers for the past 50 years. Private
      health insurance will become increasingly unaffordable to low-to-middle-income
      Americans unless major changes are made in the US health care system.

PMID- 22412009
TI  - The next phase of Title VII funding for training primary care physicians for
      America's health care needs.
AB  - Health care reform will add millions of Americans to the ranks of the insured;
      however, their access to health care is threatened by a deep decline in the
      production of primary care physicians. Poorer access to primary care risks poorer
      health outcomes and higher costs. Meeting this increased demand requires a major
      investment in primary care training. Title VII, Section 747 of the Public Health
      Service Act previously supported the growth of the health care workforce but has
      been severely cut over the past 2 decades. New and expanded Title VII initiatives
      are required to increase the production of primary care physicians; establish
      high-functioning academic, community-based training practices; increase the
      supply of well-trained primary care faculty; foster innovation and rigorous
      evaluation of these programs; and ultimately to improve the responsiveness of
      teaching hospitals to community needs. To accomplish these goals, Congress should
      act on the Council on Graduate Medical Education's recommendation to increase
      funding for Title VII, Section 747 roughly 14-fold to $560 million annually. This
      amount represents a small investment in light of the billions that Medicare
      currently spends to support graduate medical education, and both should be held
      to account for meeting physician workforce needs. Expansion of Title VII, Section
      747 with the goal of improving access to primary care would be an important part
      of a needed, broader effort to counter the decline of primary care. Failure to
      launch such a national primary care workforce revitalization program will put the
      health and economic viability of our nation at risk.

PMID- 22412010
TI  - The myth of the lone physician: toward a collaborative alternative.
AB  - Cultural values and beliefs about the primary care physician bolster the myth of
      the lone physician: a competent professional who is esteemed by colleagues and
      patients for his or her willingness to sacrifice self, accept complete
      responsibility for care, maintain continuity and accessibility, and assume the
      role of lone decision maker in clinical care. Yet the reality of current primary
      care models is often fragmented, impersonal care for patients and isolation and
      burnout for many primary care physicians. An alternative to the mythological lone
      physician would require a paradigm shift that places the primary care physician
      within the context of a highly functioning health care team. This new mythology
      better fulfills the collaborative, interprofessional, patient-centered needs of
      new models of care, and might help to ensure that the work of primary care
      physicians remains compassionate, gratifying, and meaningful.

PMID- 22412011
TI  - A family medicine residency program curriculum resource.

PMID- 22412012
TI  - The personal face of primary care research.

PMID- 22412013
TI  - Physician networking resource Delta-Exchange now free to AAFP members.

PMID- 22412015
TI  - An imperative for 2012 and beyond: step up and advocate for academic family
      medicine.

PMID- 22412016
TI  - Producing family physicians: our medical schools must do a better job.

PMID- 22412017
TI  - Balanced Ero1 activation and inactivation establishes ER redox homeostasis.
AB  - The endoplasmic reticulum (ER) provides an environment optimized for oxidative
      protein folding through the action of Ero1p, which generates disulfide bonds, and
      Pdi1p, which receives disulfide bonds from Ero1p and transfers them to substrate
      proteins. Feedback regulation of Ero1p through reduction and oxidation of
      regulatory bonds within Ero1p is essential for maintaining the proper redox
      balance in the ER. In this paper, we show that Pdi1p is the key regulator of
      Ero1p activity. Reduced Pdi1p resulted in the activation of Ero1p by direct
      reduction of Ero1p regulatory bonds. Conversely, upon depletion of thiol
      substrates and accumulation of oxidized Pdi1p, Ero1p was inactivated by both
      autonomous oxidation and Pdi1p-mediated oxidation of Ero1p regulatory bonds.
      Pdi1p responded to the availability of free thiols and the relative levels of
      reduced and oxidized glutathione in the ER to control Ero1p activity and ensure
      that cells generate the minimum number of disulfide bonds needed for efficient
      oxidative protein folding.

PMID- 22412018
TI  - A promiscuous biotin ligase fusion protein identifies proximal and interacting
      proteins in mammalian cells.
AB  - We have developed a new technique for proximity-dependent labeling of proteins in
      eukaryotic cells. Named BioID for proximity-dependent biotin identification, this
      approach is based on fusion of a promiscuous Escherichia coli biotin protein
      ligase to a targeting protein. BioID features proximity-dependent biotinylation
      of proteins that are near-neighbors of the fusion protein. Biotinylated proteins
      may be isolated by affinity capture and identified by mass spectrometry. We apply
      BioID to lamin-A (LaA), a well-characterized intermediate filament protein that
      is a constituent of the nuclear lamina, an important structural element of the
      nuclear envelope (NE). We identify multiple proteins that associate with and/or
      are proximate to LaA in vivo. The most abundant of these include known
      interactors of LaA that are localized to the NE, as well as a new NE-associated
      protein named SLAP75. Our results suggest BioID is a useful and generally
      applicable method to screen for both interacting and neighboring proteins in
      their native cellular environment.

PMID- 22412019
TI  - A stochastic model of kinetochore-microtubule attachment accurately describes
      fission yeast chromosome segregation.
AB  - In fission yeast, erroneous attachments of spindle microtubules to kinetochores
      are frequent in early mitosis. Most are corrected before anaphase onset by a
      mechanism involving the protein kinase Aurora B, which destabilizes kinetochore
      microtubules (ktMTs) in the absence of tension between sister chromatids. In this
      paper, we describe a minimal mathematical model of fission yeast chromosome
      segregation based on the stochastic attachment and detachment of ktMTs. The model
      accurately reproduces the timing of correct chromosome biorientation and
      segregation seen in fission yeast. Prevention of attachment defects requires both
      appropriate kinetochore orientation and an Aurora B-like activity. The model also
      reproduces abnormal chromosome segregation behavior (caused by, for example,
      inhibition of Aurora B). It predicts that, in metaphase, merotelic attachment is
      prevented by a kinetochore orientation effect and corrected by an Aurora B-like
      activity, whereas in anaphase, it is corrected through unbalanced forces applied
      to the kinetochore. These unbalanced forces are sufficient to prevent aneuploidy.

PMID- 22412020
TI  - Microtubule stability, Golgi organization, and transport flux require dystonin-a2
      MAP1B interaction.
AB  - Loss of function of dystonin cytoskeletal linker proteins causes
      neurodegeneration in dystonia musculorum (dt) mutant mice. Although much
      investigation has focused on understanding dt pathology, the diverse cellular
      functions of dystonin isoforms remain poorly characterized. In this paper, we
      highlight novel functions of the dystonin-a2 isoform in mediating microtubule
      (MT) stability, Golgi organization, and flux through the secretory pathway. Using
      dystonin mutant mice combined with isoform-specific loss-of-function analysis, we
      found dystonin-a2 bound to MT-associated protein 1B (MAP1B) in the centrosomal
      region, where it maintained MT acetylation. In dt neurons, absence of the MAP1B
      dystonin-a2 interaction resulted in altered MAP1B perikaryal localization,
      leading to MT deacetylation and instability. Deacetylated MT accumulation
      resulted in Golgi fragmentation and prevented anterograde trafficking via motor
      proteins. Maintenance of MT acetylation through trichostatin A administration or
      MAP1B overexpression mitigated the observed defect. These cellular aberrations
      are apparent in prephenotype dorsal root ganglia and primary sensory neurons from
      dt mice, suggesting they are causal in the disorder.

PMID- 22412022
TI  - Incidence and cost of injury among youth in agricultural settings, United States,
      2001-2006.
AB  - OBJECTIVE: Estimate the annual US incidence and cost of fatal and nonfatal youth
      injury in agricultural settings. METHODS: We used 2001-2006 Childhood
      Agricultural Injury Survey data to estimate the incidence of nonfatal injury and
      2001-2006 Multiple Cause of Death data to estimate the incidence of fatal injury.
      To estimate the costs for injuries suffered by youth working/living in
      agricultural settings, we multiplied the number of injuries times published unit
      costs by body part, nature of injury, and age group. RESULTS: An average of 26
      655 agricultural injury incidents occurred annually to youth (ages 0-19) in the
      United States during the period 2001-2006 (95% confidence interval [CI]: 24 263
      29 046). These injuries cost society an estimated $1.423 billion per year in 2005
      dollars (95% CI: $1.333 billion-$1.513 billion). Fatalities alone cost an
      estimated $420 million per year. Work related injuries annually cost $347 million
      or 24.4% of the total cost (95% CI: 20.3%-28.5%). Most agricultural youth
      injuries were not work related. CONCLUSIONS: We found that, similarly to adult
      agricultural injuries, youth agricultural injuries tend to be more severe and
      more costly than nonagricultural injuries. Only 1.4% of injured youth in the
      United States were hospitalized in 2000, but 14% of youth injured in agriculture
      were hospitalized in 2001-2006. To address this serious problem, prevention
      should focus on better controlling both child access to agricultural recreational
      activities and child assignment to agricultural work tasks that exceed
      developmental norms.

PMID- 22412021
TI  - BDNF and its pro-peptide are stored in presynaptic dense core vesicles in brain
      neurons.
AB  - Although brain-derived neurotrophic factor (BDNF) regulates numerous and complex
      biological processes including memory retention, its extremely low levels in the
      mature central nervous system have greatly complicated attempts to reliably
      localize it. Using rigorous specificity controls, we found that antibodies
      reacting either with BDNF or its pro-peptide both stained large dense core
      vesicles in excitatory presynaptic terminals of the adult mouse hippocampus. Both
      moieties were ~10-fold more abundant than pro-BDNF. The lack of postsynaptic
      localization was confirmed in Bassoon mutants, a seizure-prone mouse line
      exhibiting markedly elevated levels of BDNF. These findings challenge previous
      conclusions based on work with cultured neurons, which suggested activity
      dependent dendritic synthesis and release of BDNF. They instead provide an
      ultrastructural basis for an anterograde mode of action of BDNF, contrasting with
      the long-established retrograde model derived from experiments with nerve growth
      factor in the peripheral nervous system.

PMID- 22412023
TI  - Recognizing and managing eczematous id reactions to molluscum contagiosum virus
      in children.
AB  - Molluscum contagiosum (MC) is a self-limiting cutaneous viral eruption that is
      very common in children. MC infection can trigger an eczematous reaction around
      molluscum papules known as a hypersensitivity or an id reaction. In addition, a
      hypersensitivity reaction can occasionally occur at sites distant from the
      primary molluscum papules. These eczematous reactions are often asymptomatic or
      minimally pruritic. We believe that id reactions represent an immunologically
      mediated host response to MC virus and a harbinger of regression. Therefore,
      these reactions often do not require treatment other than emollients. Moreover,
      topical steroids or immunomodulators may suppress this process and potentiate the
      spread of the primary MC infection. However, in symptomatic patients, treatment
      should not be withheld and short-course treatments of topical corticosteroids may
      be used. In this case series, we describe 3 cases of hypersensitivity reactions
      in otherwise healthy children with MC. We hope that our report will make
      clinicians more aware of this common eczematous response to MC and will improve
      the management and counseling of these patients and their parents.

PMID- 22412024
TI  - The progressive past of residential treatment of emotionally disturbed children.

PMID- 22412025
TI  - Effect on infant illness of maternal supplementation with 400 000 IU vs 200 000
      IU of vitamin A.
AB  - BACKGROUND AND OBJECTIVE: Postpartum vitamin A supplementation is a strategy used
      to combat vitamin A deficiency and seems to reduce maternal/infant morbidity and
      mortality. However, studies have shown that a dose of 200 000 IU (World Health
      Organization [WHO] protocol) does not seem to provide adequate retinol levels in
      maternal breast milk, infant serum, and infant tissue. The objective of this
      study was to compare the effect of postpartum maternal supplementation with 400
      000 IU (International Vitamin A Consultative Group protocol) compared with 200
      000 IU of vitamin A on infant morbidity. METHODS: This was a randomized
      controlled, triple-blinded clinical trial conducted at 2 public maternity
      hospitals in Recife in northeastern Brazil. There were 276 mother-child pairs
      that were allocated to 2 treatment groups: 400 000 IU or 200 000 IU of vitamin A.
      They were followed up for >6 months to evaluate infant morbidity. RESULTS: Fever
      (rate ratio [RR]: 0.92 [95% confidence interval (CI): 0.75-1.14]), diarrhea (RR:
      0.96 [95% CI: 0.72-1.28]), otitis (RR: 0.94 [95% CI: 0.48-1.85]), acute
      respiratory infection (RR: 1.03 [95% CI: 0.88-1.21]), the need for intravenous
      rehydration (RR: 2.08 [95% CI: 0.64-2.07]), and the use of antibiotic treatment
      (RR: 0.80 [95% CI: 0.43-1.47]) did not differ significantly between the 2
      treatment groups. CONCLUSIONS: Our findings suggest that postpartum maternal
      supplementation with 400 000 IU of vitamin A does not provide any additional
      benefits in the reduction of illness in children aged <6 months; therefore, we do
      not support the proposal to increase the standard vitamin A dose in the existing
      WHO protocol.

PMID- 22412026
TI  - Behavioral and social phenotypes in boys with 47,XYY syndrome or 47,XXY
      Klinefelter syndrome.
AB  - OBJECTIVE: To contrast the behavioral and social phenotypes including a screen
      for autistic behaviors in boys with 47,XYY syndrome (XYY) or 47,XXY Klinefelter
      syndrome (KS) and controls and investigate the effect of prenatal diagnosis on
      the phenotype. METHODS: Patients included 26 boys with 47,XYY, 82 boys with KS,
      and 50 control boys (ages 4-15 years). Participants and parents completed a
      physical examination, behavioral questionnaires, and intellectual assessments.
      RESULTS: Most boys with XYY or KS had Child Behavior Checklist parental ratings
      within the normal range. On the Child Behavior Checklist, mean problem behaviors
      t scores were higher in the XYY versus KS groups for the Problem Behavior,
      Externalizing, Withdrawn, Thought Problems, and Attention Problems subscales. On
      the Conners' Parent Rating Scale-Revised, the XYY versus KS group had increased
      frequency of hyperactive/impulsive symptoms (P < .006). In addition, 50% and 12%
      of the XYY and KS groups, respectively, had scores >15 for autism screening from
      the Social Communication Questionnaire. For the boys with KS, prenatal diagnosis
      was associated with fewer problem behaviors. CONCLUSIONS: A subset of the XYY and
      KS groups had behavioral difficulties that were more severe in the XYY group.
      These findings could guide clinical practice and inform patients and parents.
      Boys diagnosed with XYY or KS should receive a comprehensive psychoeducational
      evaluation and be screened for learning disabilities, attention
      deficit/hyperactivity disorder, and autism spectrum disorders.

PMID- 22412027
TI  - Parental psychological well-being and behavioral outcome of very low birth weight
      infants at 3 years.
AB  - OBJECTIVE: The purpose was to explore whether poor parental psychological well
      being is associated with behavioral problems of very low birth weight (VLBW,
      <=1500 g) infants at 3 years of age. METHODS: In this prospective cohort study,
      189 VLBW preterm infants born between January 2001 and December 2006 at the Turku
      University Hospital, Finland, were followed. Validated questionnaires (Beck
      Depression Inventory, Parenting Stress Index, and Sense of Coherence Scale) were
      mailed to the parents when their children were 2 years corrected age. A total of
      140 parents evaluated the behavior of the child at 3 years by filling out the
      Child Behavior Checklist. RESULTS: There were significant associations between
      most of the measures of parental symptoms of depression, parenting stress, and
      sense of coherence and the behavioral outcome of the VLBW infants. The
      concomitant symptoms of both parents were associated with more problematic child
      behavior. CONCLUSIONS: Parents report more behavioral and emotional problems in
      VLBW children at age 3 if they themselves have had symptoms of depression,
      parenting stress, or weak sense of coherence 1 year earlier. The new finding of
      this study was to show the significance of the father's psychological well-being
      on the behavioral development of a preterm child.

PMID- 22412028
TI  - Hospital variation in nitric oxide use for premature infants.
AB  - OBJECTIVE: To describe inter-center hospital variation in inhaled nitric oxide
      (iNO) administration to infants born prior to 34 weeks' gestation at US
      children's hospitals. METHODS: This was a retrospective cohort study using the
      Pediatric Health Information System to determine the frequency, age at first
      administration, and length of iNO use among 22 699 consecutive first admissions
      of unique <34 weeks' gestation infants admitted to 37 children's hospitals from
      January 1, 2007, through December 31, 2010. RESULTS: A total of 1644 (7.2%)
      infants received iNO during their hospitalization, with substantial variation in
      iNO use between hospitals (range across hospitals: 0.5%-26.2%; P < .001). The age
      at which iNO was started varied by hospital (mean: 20.0 days; range: 6.0-65.1
      days, P < .001), as did the duration of therapy (mean: 13.1 days; range: 1.0-31.1
      days; P < .001). Preterm infants who received iNO were less likely to survive
      (36.3% mortality vs 8.3%; odds ratio: 6.27; P < .001). The association between
      the use of iNO and mortality persists in propensity score-adjusted analyses
      controlling for demographic factors and diagnoses associated with the use of iNO
      (odds ratio: 3.79; P < .0001). CONCLUSIONS: iNO practice patterns in preterm
      infants varied widely among institutions. Infants who received iNO were less
      likely to survive, suggesting that iNO is used in infants already at high risk of
      death. Adherence to National Institutes of Health consensus guidelines may
      decrease variation in iNO use.

PMID- 22412029
TI  - Late delirious behavior with 2009 H1N1 influenza: mild autoimmune-mediated
      encephalitis?
AB  - Delirious behavior associated with influenza usually has an onset within a few
      days after fever and lasts <24 hours. As we encountered several patients with
      2009 H1N1 influenza who presented with late-onset and long-standing delirious
      behavior, we retrospectively evaluated the clinical, radiologic, and laboratory
      features to elucidate the possible pathophysiology. This information was
      collected on 5 previously healthy patients (2 boys and 3 girls, aged 10-15 years)
      with 2009 H1N1 influenza who presented with late onset (>3 days after fever) and
      long-standing (>48 hours) delirious behavior. Each exhibited mild to moderate
      drowsiness between the episodes of delirious behavior. Electroencephalography was
      normal except for 1 patient with high voltage and slow activity bilaterally in
      the occipital regions. Brain MRI was normal. The outcome was excellent with no
      neurologic sequel in 4 of the 5 patients. In all 5 patients, autoantibodies
      against N-methyl-D-aspartate type glutamate receptor were elevated or positive in
      cerebrospinal fluid or serum; the autoantibody levels normalized in the 3
      patients who had follow-up studies. This study indicates that 2009 H1N1 influenza
      has a tendency to cause late-onset and long-standing delirious behavior, at least
      in Japanese children. Mild autoimmune-mediated encephalitis should be considered
      as an underlying cause.

PMID- 22412031
TI  - Stair-related injuries to young children treated in US emergency departments,
      1999-2008.
AB  - OBJECTIVE: The objective of this study was to investigate the epidemiologic
      characteristics and secular trends of stair-related injuries among children aged
      <5 years treated in US emergency departments. METHODS: A retrospective analysis
      was conducted of data from the National Electronic Injury Surveillance System of
      the US Consumer Product Safety Commission from 1999 through 2008 by using sample
      weights to estimate national numbers and rates of stair-related injuries.
      RESULTS: An estimated 931 886 children aged <5 years were treated for stair
      related injuries from 1999 through 2008, averaging 93 189 injuries per year and
      46.5 injuries per 10 000 population annually. The number of injuries per year
      decreased significantly by 11.6% from 1999 to 2008. The rate of stair-related
      injuries also decreased significantly from 53.0 to 42.4 per 10 000 population
      from 1999 to 2008. Soft tissue injuries accounted for 34.6% of cases.
      Approximately three-fourths (76.3%) of children had injuries to the head and neck
      region, and 2.7% of patients were hospitalized. Children who were being carried
      at the time of injury accounted for 24.5% of injuries among children <1 year and
      were more than 3 times more likely to be hospitalized than children injured by
      other mechanisms. CONCLUSIONS: Stair-related injuries are on the decline but
      still represent an important source of injury to young children. Increased
      prevention efforts are needed, including parental education and improved stairway
      design, to decrease stair-related injuries among young children.

PMID- 22412030
TI  - Improved outcomes in a quality improvement collaborative for pediatric
      inflammatory bowel disease.
AB  - OBJECTIVES: Unintended variation in the care of patients with Crohn disease (CD)
      and ulcerative colitis (UC) may prevent achievement of optimal outcomes. We
      sought to improve chronic care delivery and outcomes for children with
      inflammatory bowel disease by using network-based quality improvement methods.
      METHODS: By using a modified Breakthrough Series collaborative structure, 6
      ImproveCareNow Network care centers tested changes in chronic illness care and
      collected data monthly. We used an interrupted time series design to evaluate the
      impact of these changes. RESULTS: Data were available for 843 children with CD
      and 345 with UC. Changes in care delivery were associated with an increase in the
      proportion of visits with complete disease classification, measurement of
      thiopurine methyltransferase (TPMT) before initiation of thiopurines, and
      patients receiving an initial thiopurine dose appropriate to their TPMT status.
      These were significant in both populations for all process variables (P < .01)
      except for measurement of TPMT in CD patients (P = .12). There were significant
      increases in the proportion of CD (55%-68%) and UC (61%-72%) patients with
      inactive disease. There was also a significant increase in the proportion of CD
      patients not taking prednisone (86%-90%). Participating centers varied in the
      success of achieving these changes. CONCLUSIONS: Improvements in the outcomes of
      patients with CD and UC were associated with improvements in the process of
      chronic illness care. Variation in the success of implementing changes suggests
      the importance of overcoming organizational factors related to quality
      improvement success.

PMID- 22412032
TI  - Response to the AAP Section on Urology concerns about the AAP Urinary Tract
      Infection Guideline.

PMID- 22412033
TI  - Section on Urology response to new Guidelines for the diagnosis and management of
      UTI.

PMID- 22412034
TI  - Hypercalcemia in children receiving pharmacologic doses of vitamin D.
AB  - Vitamin D deficiency causes rickets, requiring vitamin D at doses greater than
      daily dietary intake. Several treatment regimens are found in the literature,
      with wide dosing ranges, inconsistent monitoring schedules, and lack of age
      specific guidelines. We describe 3 children, ages 2 weeks to 2 and 9/12 years,
      who recently presented to our institution with hypercalcemia and hypervitaminosis
      D (25-hydroxyvitamin D levels >75 ng/mL), associated with treatment of documented
      or suspected vitamin D-deficient rickets. The doses of vitamin D used were within
      accepted guidelines and believed to be safe. The patients required between 6
      weeks and 6 months to correct the elevated serum calcium, with time to resolution
      of hypercalcemia related to age and peak serum calcium, but not to peak 25
      hydroxyvitamin D level. With recent widespread use of vitamin D in larger dosages
      in the general population, we provide evidence that care must be taken when using
      pharmacologic dosing in small children. With limited dosing guidelines available
      on a per weight basis, the administration of dosages to infants that are often
      used in older children and adults has toxic potential, requiring a cautious
      approach in dose selection and careful follow-up. Dosage recommendations may need
      to be reassessed, in particular, where follow-up and monitoring may be
      compromised.

PMID- 22412035
TI  - Rising national prevalence of life-limiting conditions in children in England.
AB  - BACKGROUND: Life-limiting conditions (LLCs) describe diseases with no reasonable
      hope of cure that will ultimately be fatal. For children with these diseases,
      palliative care services should be available but few data are available to
      estimate the burden of these conditions. METHODS: Children (0-19 years) with LLCs
      were identified within an English Hospital Episode Statistics dataset (2000/2001
      2009/2010) by applying a customized coding framework of the International
      Classification of Diseases, 10th Revision, disease codes. Prevalence per 10 000
      population (0-19 years) was calculated by age, diagnostic group, ethnicity,
      deprivation, and region for each year. RESULTS: The Hospital Episode Statistics
      extract contained 175 286 individuals with 1 or more LLCs of which congenital
      anomalies were the most common (31%). Prevalence increased over 10 years from 25
      to 32 per 10 000 population. Prevalence in the South Asian (48 per 10 000); black
      (42 per 10 000); and Chinese, mixed, and "other" (31 per 10 000) populations were
      statistically significantly higher compared with the white population (27 per 10
      000). Prevalence shows an inverse J-shaped relationship with 5 categories of
      deprivation, with the highest prevalence in the most deprived areas and the
      lowest in the second least deprived. CONCLUSIONS: In 2010, the prevalence of LLCs
      in children in England was double the previously reported estimates and had
      increased annually in all areas over the past decade. This clearly identifies an
      escalating need for specialist pediatric palliative care services. When planning
      services for these increasing needs, the excess prevalence in ethnic minority
      groups, especially in deprived areas, needs to be considered.

PMID- 22412037
TI  - Assessing the utility of venous thrombosis prophylaxis in orthopedic surgery
      patients.

PMID- 22412038
TI  - Oral direct Factor Xa inhibitors versus low-molecular-weight heparin to prevent
      venous thromboembolism in patients undergoing total hip or knee replacement: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Thromboembolic disease is the most frequent medical complication of
      arthroplasty. PURPOSE: To evaluate the benefits and harms of oral direct factor
      Xa inhibitors versus low-molecular-weight heparin (LMWH) in patients undergoing
      total hip or knee replacement. DATA SOURCES: MEDLINE (1966 to December 2011),
      EMBASE (1980 to December 2011), and the Cochrane Central Register of Controlled
      Trials (up to December 2011), without language restrictions. References of
      reviews and abstracts of conferences were hand-searched. STUDY SELECTION:
      Randomized trials in patients undergoing hip or knee replacement that evaluated
      factor Xa inhibitors versus LMWH. DATA EXTRACTION: Two reviewers independently
      evaluated eligibility, abstracted the data, and assessed risk for bias. DATA
      SYNTHESIS: In 22 trials, high-quality evidence indicated that the absolute effect
      of factor Xa inhibitors and LMWH does not differ in terms of all-cause mortality
      (risk difference, 0 fewer deaths per 1000 patients [95% CI, 2 fewer to 1 more
      death]) or nonfatal pulmonary embolism (risk difference, 0 fewer events per 1000
      patients [CI, 1 fewer to 2 more events]). Factor Xa inhibitors can prevent 4
      instances of symptomatic deep venous thrombosis per 1000 treated patients (CI, 3
      to 6 fewer events; high-quality evidence) but may increase major bleeding by 2
      more events per 1000 patients (CI, 0 to 4 more events; moderate-quality
      evidence). High, but not lower, doses of oral factor Xa inhibitors increased
      bleeding compared with LMWH. LIMITATIONS: Most trials did not report outcome data
      for a substantial proportion of the patients. In 9 trials, the follow-up period
      was 14 days or less. CONCLUSION: Compared with LMWH, lower doses of oral factor
      Xa inhibitors can achieve a small absolute risk reduction in symptomatic deep
      venous thrombosis without increasing bleeding.

PMID- 22412036
TI  - Methicillin-resistant and susceptible Staphylococcus aureus bacteremia and
      meningitis in preterm infants.
AB  - BACKGROUND: Data are limited on the impact of methicillin-resistant
      Staphylococcus aureus (MRSA) on morbidity and mortality among very low birth
      weight (VLBW) infants with S aureus (SA) bacteremia and/or meningitis (B/M).
      METHODS: Neonatal data for VLBW infants (birth weight 401-1500 g) born January 1,
      2006, to December 31, 2008, who received care at centers of the Eunice Kennedy
      Shriver National Institute of Child Health and Human Development Neonatal
      Research Network were collected prospectively. Early-onset (<=72 hours after
      birth) and late-onset (>72 hours) infections were defined by blood or
      cerebrospinal fluid cultures and antibiotic treatment of >=5 days (or death <5
      days with intent to treat). Outcomes were compared for infants with MRSA versus
      methicillin-susceptible S aureus (MSSA) B/M. RESULTS: Of 8444 infants who
      survived >3 days, 316 (3.7%) had SA B/M. Eighty-eight had MRSA (1% of all
      infants, 28% of infants with SA); 228 had MSSA (2.7% of all infants, 72% of
      infants with SA). No infant had both MRSA and MSSA B/M. Ninety-nine percent of
      MRSA infections were late-onset. The percent of infants with MRSA varied by
      center (P < .001) with 9 of 20 centers reporting no cases. Need for mechanical
      ventilation, diagnosis of respiratory distress syndrome, necrotizing
      enterocolitis, and other morbidities did not differ between infants with MRSA and
      MSSA. Mortality was high with both MRSA (23 of 88, 26%) and MSSA (55 of 228,
      24%). CONCLUSIONS: Few VLBW infants had SA B/M. The 1% with MRSA had morbidity
      and mortality rates similar to infants with MSSA. Practices should provide equal
      focus on prevention and management of both MRSA and MSSA infections among VLBW
      infants.

PMID- 22412039
TI  - Prolonged versus standard-duration venous thromboprophylaxis in major orthopedic
      surgery: a systematic review.
AB  - BACKGROUND: The optimal duration of thromboprophylaxis after major orthopedic
      surgery is unclear. PURPOSE: To compare the benefits and harms of prolonged
      versus standard-duration thromboprophylaxis after major orthopedic surgery in
      adults. DATA SOURCES: Cochrane Central Register of Controlled Trials and Scopus
      from 1980 to July 2011 and MEDLINE from 1980 through November 2011, without
      language restrictions. STUDY SELECTION: Randomized trials reporting
      thromboembolic or bleeding outcomes that compared prolonged (>=21 days) with
      standard-duration (7 to 10 days) thromboprophylaxis. DATA ABSTRACTION: Two
      independent reviewers abstracted data and rated study quality and strength of
      evidence. DATA SYNTHESIS: Eight randomized, controlled trials (3 good-quality and
      5 fair-quality) met the inclusion criteria. High-strength evidence showed that
      compared with standard-duration therapy, prolonged prophylaxis resulted in fewer
      cases of pulmonary embolism (PE) (5 trials; odds ratio [OR], 0.14 [95% CI, 0.04
      to 0.47]; absolute risk reduction [ARR], 0.8%), asymptomatic deep venous
      thrombosis (DVT) (4 trials; relative risk [RR], 0.48 [CI, 0.31 to 0.75]; ARR,
      5.8%), symptomatic DVT (4 trials; OR, 0.36 [CI, 0.16 to 0.81]; ARR, 1.5%), and
      proximal DVT (6 trials; RR, 0.29 [CI, 0.16 to 0.52]; ARR, 7.1%). Moderate
      strength evidence showed fewer symptomatic objectively confirmed episodes of
      venous thromboembolism (4 trials; RR, 0.38 [CI, 0.19 to 0.77]; ARR, 5.7%),
      nonfatal PE (4 trials; OR, 0.13 [CI, 0.03 to 0.54]; ARR, 0.7%), and DVT (7
      trials; RR, 0.37 [CI, 0.21 to 0.64]; ARR, 12.1%) with prolonged prophylaxis. High
      strength evidence showed more minor bleeding events with prolonged prophylaxis
      (OR, 2.44 [CI, 1.41 to 4.20]; absolute risk increase, 6.3%), and insufficient
      evidence from 1 trial on hip fracture surgery suggested more surgical-site
      bleeding events (OR, 7.55 [CI, 1.51 to 37.64]) with prolonged prophylaxis.
      LIMITATIONS: Data relevant to knee replacement or hip fracture surgery were scant
      and insufficient. Most trials had few events; the strength of evidence ratings
      that were used may not adequately capture uncertainty in such situations.
      CONCLUSION: Prolonged prophylaxis decreases the risk for venous thromboembolism,
      PE, and DVT while increasing the risk for minor bleeding in patients undergoing
      total hip replacement.

PMID- 22412041
TI  - Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in
      early-stage breast cancer: the randomized phase 3 HOBOE study.
AB  - BACKGROUND: To measure bone mineral density (BMD) reduction produced by letrozole
      as compared with tamoxifen and the benefit of the addition of zoledronic acid.
      PATIENTS AND METHODS: A phase 3 trial comparing tamoxifen, letrozole or
      letrozole+zoledronic acid in patients with hormone receptor-positive early breast
      cancer was conducted; triptorelin was given to premenopausal patients. Two
      comparisons were planned: letrozole versus tamoxifen and letrozole+zoledronic
      acid versus letrozole. Primary end point was the difference in 1-year change of T
      score at lumbar spine (LTS) measured by dual energy X-ray absorptiometry scan.
      RESULTS: Out of 483 patients enrolled, 459 were available for primary analyses.
      Median age was 50 (range 28-80). The estimated mean difference (95% confidence
      interval [CI]) in 1-year change of LTS was equal to -0.30 (95% CI -0.44 to -0.17)
      in the letrozole versus tamoxifen comparison (P<0.0001) and to +0.60 (95% CI
      +0.46 to +0.77) in the letrozole+zoledronic acid versus letrozole comparison
      (P<0.0001). Bone damage by letrozole decreased with increasing baseline body mass
      index in premenopausal, but not postmenopausal, patients (interaction test
      P=0.004 and 0.47, respectively). CONCLUSIONS: In the HOBOE (HOrmonal BOne
      Effects) trial, the positive effect of zoledronic acid on BMD largely counteracts
      damage produced by letrozole as compared with tamoxifen. Letrozole effect is
      lower among overweight/obese premenopausal patients.

PMID- 22412042
TI  - HER2-negative (1+) breast cancer with unfavorable prognostic features: to FISH or
      not to FISH?

PMID- 22412043
TI  - Male patients with partial androgen insensitivity syndrome: a longitudinal follow
      up of growth, reproductive hormones and the development of gynaecomastia.
AB  - OBJECTIVE: To describe the natural history of phenotype, growth and gonadal
      function in patients with partial androgen insensitivity syndrome. SETTING:
      Tertiary paediatric endocrine centre. METHODS: Retrospective evaluation of 14
      male patients with partial androgen insensitivity syndrome (PAIS) with verified
      androgen receptor (AR) mutations. The authors recorded phenotypic characteristics
      at birth and external masculinisation score (EMS), registered longitudinal
      growth, circulating levels of testosterone, estradiol, luteinising hormone (LH),
      follicle-stimulating hormone (FSH), inhibin-B and sex hormone binding globulin
      (SHBG), in addition to phenotype at postpubertal follow up. RESULTS: The EMS
      ranged from 5 to 12 in PAIS at birth. Six patients were born with hypospadias and
      all patients developed gynaecomastia in puberty. Eight of the patients received
      testosterone treatment. At follow-up penile size was impaired irrespective of EMS
      at birth, but responded to pubertal androgen therapy in some of the patients.
      Serum levels of testosterone, estradiol, SHBG and LH, but not FSH and inhibin B,
      were markedly elevated in puberty. Final height was 181.3 cm (165.7-190.5 cm)
      corresponding to an SD score of 0.7 (-2.1 to +2.1 SD, n=10). CONCLUSION:
      Gynaecomastia and impaired phallic growth are frequently observed in adults with
      PAIS, but may be ameliorated by androgen therapy. The authors suggest that male
      patients presenting with gynaecomastia in puberty, and elevated circulating
      levels of testosterone, estradiol and LH in puberty, but normal FSH, should be
      suspected of having PAIS and undergo genetic testing for AR mutations.

PMID- 22412044
TI  - Twenty years experience of selective secondary ultrasound screening for
      congenital dislocation of the hip.
AB  - OBJECTIVES: The authors report the results of a selective ultrasound screening
      programme for congenital dislocation of the hip (CDH) over a period of 20 years,
      with the aim of defining the rate of screening, conservative treatment and late
      presentation requiring surgery. METHODS: All neonates born from June 1988 to
      December 2008 (inclusive) were included in the prospective cohort, with a minimum
      follow-up of 12 months. All underwent an early clinical examination of the hips
      and those with clinical instability were referred for ultrasound at 2 weeks;
      those with risk factors were sonographically examined at 6 weeks. Risk factors
      were defined as breech presentation, family history or foot deformity. RESULTS:
      107 440 live births were clinically examined, 20 344 (18.9%) were referred for
      ultrasound assessment at either 2 weeks (due to clinical signs) or 6 weeks (due
      to risk factors). 774 (3.8%) were diagnosed with dysplasia with a crude overall
      treatment rate of 7.2 per 1000 live births. 37 (0.34 per 1000) presented late,
      that is, after 12 weeks of age; none had detectable clinical signs or risk
      factors. There were no false negatives. CONCLUSION: Elective screening for
      developmental dysplasia of the hip in association with one stop treatment and
      monitoring is an effective programme. The number of infants referred increased
      statistically significantly year on year over the study period and generated more
      activity. Pavlik harness treatment rates remained acceptable and steady over the
      period, despite the increase in referrals. The incidence of late presenting cases
      ranged from 0 to 4 per year, with no secular trend and there were no ultrasound
      false negatives.

PMID- 22412045
TI  - HER2 expression in ovarian carcinoma: caution and complexity in biomarker
      analysis.

PMID- 22412046
TI  - Wnt signalling pathway in the serrated neoplastic pathway of the colorectum:
      possible roles and epigenetic regulatory mechanisms.
AB  - The role of Wnt signalling in the serrated neoplastic pathway of colorectal
      tumourigenesis appears to be heterogeneous. Wnt pathway abnormalities contribute
      to the progression of at least a subset of traditional serrated adenomas of the
      colorectum, but may play a less active role in its pathogenesis compared with
      that in conventional adenoma-carcinoma. However, immunohistochemical studies of
      beta-catenin in sessile serrated adenomas have shown wide variability, producing
      conflicting results on Wnt signalling activation in sessile serrated adenomas.
      DNA methylation, involving APC, SFRPs and mutated in colorectal cancer (MCC), may
      bridge the mutational gap of APC or beta-catenin for activating Wnt signalling in
      serrated adenomas of the colorectum.

PMID- 22412047
TI  - Determination of serum aldosterone by liquid chromatography and tandem mass
      spectrometry: a liquid-liquid extraction method for the ABSCIEX API-5000 mass
      spectrometry system.
AB  - AIMS: Accurate serum aldosterone determination is critical to the screening and
      diagnosis of primary aldosteronism, the localisation of aldosterone producing
      tumours, and the investigation of other disorders of the renin-angiotensin
      system. Mass spectrometry offers a means to overcome problems with method
      dependent bias between competitive immunoassays for aldosterone. The authors have
      developed a simple, sensitive and precise liquid-liquid extraction aldosterone
      method for the ABSCIEX API-5000 liquid chromatography and tandem mass
      spectrometry (LC-MS/MS) system. METHODS: Using d7-aldosterone internal standard,
      500 MUl of sample is extracted with 2500 MUl of methyl tertbutyl ether followed
      by dry-down, reconstitution and LC-MS/MS analysis in ESI negative mode. Method
      validation was undertaken using standard approaches and comparison made against a
      commercial radioimmunoassay. Accuracy was assessed using EQA material with
      assigned aldosterone concentrations. RESULTS: The assay was linear up to 3420
      pmol/l (LOQ=50 pmol/l, LOD<22 pmol/l). Total CVs were <=5% for concentrations
      >=120 pmol/l and 10% at the LOQ. Mean accuracy was 98.5% against GCMS assigned
      material. CONCLUSION: The authors present a precise, sensitive and simple
      aldosterone method suitable for routine clinical use that requires no solid phase
      extraction or specialised ion sources.

PMID- 22412048
TI  - Metaplastic breast cancer: clinicopathological features and its prognosis.
AB  - AIMS: The prognosis of metaplastic breast cancer (MBC) is reportedly worse than
      that of triple-negative invasive ductal carcinoma (TN-IDC), but the determinants
      of poor prognosis are not yet known. METHODS: Patients from two Korean cancer
      centres were included in this study (67 MBC and 520 TN-IDC). Characteristics of
      the two disease groups, including clinical parameters, histological features,
      chemoresponsiveness, disease recurrence and survival estimates, were evaluated.
      RESULTS: MBC presented with larger tumours, more frequent distant metastasis and
      higher histological grade compared with TN-IDC (p<0.001). All but nine patients
      with MBC had triple-negative disease. Disease-free survival and overall survival
      (OS) of MBC were worse than TN-IDC (p<0.001). Multivariable analysis of disease
      free survival revealed MBC type as an independent prognostic factor (HR 2.53; 95%
      CI 1.32 to 4.84) along with lymph node metastasis and implementation of breast
      conserving surgery. For OS, MBC type remained a significant prognostic factor (HR
      2.56; 95% CI 1.18 to 5.54). Chemoresponsiveness of MBC and TN-IDC were similar in
      both neoadjuvant (p=1.000) and advanced disease settings (p=0.508). For a given
      MBC type, risk factors for disease recurrence included the presence of a squamous
      component (HR 4.0; 95% CI 1.46 to 10.99) and lymph node metastasis (HR 4.76; 95%
      CI 1.67 to 13.60); the risk factor for OS was initial distant metastasis (HR
      10.77; 95% CI 2.59 to 44.76). CONCLUSIONS: MBC had worse survival outcomes
      compared with TN-IDC. Poor prognosis for MBC was likely caused by frequent
      recurrence with high initial stage and the unique biology of MBC itself.

PMID- 22412049
TI  - The neurofibromin 1 type I isoform predominance characterises female population
      affected by sporadic breast cancer: preliminary data.
AB  - AIMS: Neurofibromin 1 (NF1) as a tumour suppressor gene can give rise to several
      transcripts by an alternative splicing event, generated at least for CELF
      cofactors. At present, the NF1 isoforms and CELF splicing transcripts in sporadic
      breast cancer are unknown. The aim of the authors was to detect NF1 gene
      expression, the NF1 isoform ratio and the CELF transcripts present in sporadic
      breast cancer. METHODS: Neurofibromin and RAS expression were analysed on tissue
      microarrays containing sporadic breast cancer (n=22), benign lesions (n=18,
      including six fibroadenomas, six fibrocystic changes and six ductal hyperplasias)
      and normal breast tissue (n=6) by immunohistochemistry assay. NF1 and CELF 3-6
      RNA expression was performed by end point reverse transcription-PCR in the breast
      samples. RESULTS: NF1 and RAS expression in breast tissues showed no differential
      expression by immunohistochemistry results. Interestingly, the authors observed a
      shift transition in the isoform transcripts, from type II in normal breast tissue
      to type I isoform in breast carcinomas. CELF cofactor expression failed to be
      related with the shift transition of NF1 in breast tissues. CONCLUSIONS: These
      data suggest that there is a tendency for an NF1 expression shift transition from
      type II to type I isoform, which could comprise a significant event in the
      development and progression of sporadic breast cancer. This shift transition may
      not be related with CELF cofactors.

PMID- 22412050
TI  - Epidermal growth factor receptor mutations in malignant pleural and peritoneal
      mesothelioma.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutation at the kinase
      domain and EGFR gene amplification are reported to be predictors of the response
      to EGFR tyrosine kinase inhibitors in lung cancer cases. In malignant
      mesothelioma (MM), the role of EGFR is less clear. METHODS: Thirty-eight MM
      specimens were submitted to EGFR mutation evaluation, and compared with the
      results of immunohistochemical staining and fluorescence in situ hybridization
      (FISH) analysis. DNA was extracted from paraffin blocks and PCR was performed to
      amplify exon regions 18-21 of the EGFR gene. Direct sequencing of the purified
      PCR products was performed. RESULTS: Five EGFR missense mutations were detected
      in six of the 38 patients (16%); two of these mutations were novel, two were
      originally detected in non-small cell lung carcinoma, and one resembled a
      location previously noted for malignant peritoneal mesothelioma. CONCLUSION: As
      far as the authors are aware there has been no report of the EGFR mutation of MM
      in Japanese cases, but in this study EGFR missense mutations were detected in
      some cases. EGFR mutation results were not related to immunohistochemical and
      FISH analysis.

PMID- 22412051
TI  - Enhanced biomedical scientist cut-up role in colonic cancer reporting.
AB  - AIMS: To extend the biomedical scientist (BMS) cut-up role to include
      gastrointestinal category D colorectal cancer resection specimens, and to address
      issues of quality and safety by presenting performance data from the first 50 BMS
      cut-up specimens in comparison with national guidelines and pathologist
      performance over the same timeframe. METHODS: Close mentoring and consultant
      supervision was carried out for every case with adherence to standard operating
      procedures and following colorectal cancer dataset guidelines as published by the
      Royal College of Pathologists. Performance targets were audited including
      anticipated spread of Dukes' stage, targets for mean lymph node harvest,
      percentage extramural vascular invasion and serosal involvement, and mean tumour
      blocks sampled. Histological pre-reporting of 20 cases was encouraged, and time
      spent by BMS and consultant at all stages of specimen reporting was noted.
      RESULTS: Performance targets were all exceeded by the BMS and compared favourably
      with pathologist performance. A measure of consultant cut-up and histology
      reporting time saved was identified. CONCLUSIONS: Benefits of extending the BMS
      role to category D specimens may include BMS professional advancement, efficient
      use of consultant time and the development of a team approach to cancer
      reporting. The achievement of colorectal cancer performance targets and
      favourable comparison with pathologist performance implies there was no perceived
      detrimental effect on quality or safety and thus patient management.

PMID- 22412052
TI  - Troponin testing in the emergency department: a longitudinal study to assess the
      impact and sustainability of decision support strategies.
AB  - AIM: To evaluate the impact of decision support on the proportion of troponin I
      (cTnI) tests and associated costs over the period 2000-7 for patients presenting
      with chest pain in an emergency department (ED) setting. METHODS: A longitudinal
      study using linked data for patients presenting with chest pain from the ED and
      laboratory information systems of a metropolitan teaching hospital in Melbourne,
      Australia. The study period was divided into a pre-intervention period (2000-2),
      which contained no decision support; an initial post period (2003-4) after the
      introduction of a quality improvement initiative (utilising a paper-based
      guideline, education, audit and feedback) about cTnI test ordering and the
      incorporation of the guideline as a decision support feature of the computerised
      provider order entry system; followed by a post-modification period (2005-7)
      after the electronic decision support feature was modified to allow clinicians to
      bypass viewing the complete guideline. RESULTS: There was a significant fall in
      the proportion of cTnI tests ordered per patient presentation across the three
      periods-pre (2000-2), post (2003-4) and post-modification (2005-7)-from 7.3% to
      4.1% and 2.8%, respectively. Analysis of costs showed significant reductions in
      the mean costs for cTnI tests per patient presentation from $A9.28 to $A8.54 and
      $A8.18, respectively, which amounted to a modest saving of $A13,251 since the
      initiation of decision support in 2003. CONCLUSIONS: Decision support systems are
      often part of multifaceted implementations undertaken over time. They require
      continuous monitoring and modifications to ensure optimal performance.

PMID- 22412053
TI  - Resolution of post-polycythaemic myelofibrosis with a combination of thalidomide
      and interferon.

PMID- 22412054
TI  - Clinicopathological significance of podocalyxin and phosphorylated ezrin in
      uterine endometrioid adenocarcinoma.
AB  - BACKGROUND: Podocalyxin is an anti-adhesive glycoprotein that has been associated
      with highly aggressive forms of cancers. Podocalyxin increases the migration and
      invasive properties of cancer cells through its interaction with ezrin, which
      undergoes an increase in phosphorylation through podocalyxin. AIMS: To study the
      roles of podocalyxin and phosphorylated ezrin (pEzrin) in uterine endometrioid
      adenocarcinoma (UEA). METHODS: Using immunohistochemisty the authors investigated
      the expression of podocalyxin and pEzrin along with some well-known markers of
      tumour aggressiveness including p53, oestrogen receptor and Ki-67 in UEA.
      RESULTS: Podocalyxin and pEzrin expression levels were positive in 36.1% (22 of
      61 patients) and 50.8% (31 of 61 patients) of UEA cases, respectively. Further,
      podocalyxin expression was correlated with tumour grade (p=0.0001), FIGO stage
      (p=0.0062), p53 expression (p=0.0050) and Ki-67 index (p=0.0069). In addition,
      pEzrin expression was associated with FIGO stage (p=0.0231), p53 expression
      (p<0.0001) and Ki-67 index (p=0.0010). The expression of podocalyxin was also
      correlated with that of pEzrin (p=0.0102). CONCLUSIONS: These results suggest
      that overexpression of podocalyxin and pEzrin may indicate a more aggressive
      phenotype; thus, evaluation of these proteins may be useful in prediction of
      disease progression in UEA cases.

PMID- 22412055
TI  - Impact of treatment strategy on outcomes in patients with candidemia and other
      forms of invasive candidiasis: a patient-level quantitative review of randomized
      trials.
AB  - BACKGROUND: Invasive candidiasis (IC) is an important healthcare-related
      infection, with increasing incidence and a crude mortality exceeding 50%.
      Numerous treatment options are available yet comparative studies have not
      identified optimal therapy. METHODS: We conducted an individual patient-level
      quantitative review of randomized trials for treatment of IC and to assess the
      impact of host-, organism-, and treatment-related factors on mortality and
      clinical cure. Studies were identified by searching computerized databases and
      queries of experts in the field for randomized trials comparing the effect of >=2
      antifungals for treatment of IC. Univariate and multivariable analyses were
      performed to determine factors associated with patient outcomes. RESULTS: Data
      from 1915 patients were obtained from 7 trials. Overall mortality among patients
      in the entire data set was 31.4%, and the rate of treatment success was 67.4%.
      Logistic regression analysis for the aggregate data set identified increasing age
      (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02; P = .02), the
      Acute Physiology and Chronic Health Evaluation II score (OR, 1.11; 95% CI, 1.08
      1.14; P = .0001), use of immunosuppressive therapy (OR, 1.69; 95% CI, 1.18-2.44;
      P = .001), and infection with Candida tropicalis (OR, 1.64; 95% CI, 1.11-2.39; P
      = .01) as predictors of mortality. Conversely, removal of a central venous
      catheter (CVC) (OR, 0.50; 95% CI, .35-.72; P = .0001) and treatment with an
      echinocandin antifungal (OR, 0.65; 95% CI, .45-.94; P = .02) were associated with
      decreased mortality. Similar findings were observed for the clinical success end
      point. CONCLUSIONS: Two treatment-related factors were associated with improved
      survival and greater clinical success: use of an echinocandin and removal of the
      CVC.

PMID- 22412056
TI  - Active case finding and prevention of tuberculosis among a cohort of contacts
      exposed to infectious tuberculosis cases in New York City.
AB  - BACKGROUND: Tuberculosis contact investigation identifies individuals who may be
      recently infected with tuberculosis and are thus at increased risk for disease.
      Contacts with latent tuberculosis infection (LTBI) are offered chemoprophylaxis
      to prevent active disease; however, the effectiveness of this intervention is
      unclear as treatment completion is generally low. METHODS: A retrospective cohort
      study of 30 561 contacts identified during investigation of 5182 cases of
      tuberculosis diagnosed in New York City, 1997-2003, was performed. We searched
      the NYC tuberculosis registry to identify contacts developing active tuberculosis
      within 4 years of follow-up. We estimated the following: number of contacts
      undergoing evaluation (ie, tuberculin skin test and/or chest radiograph) per
      prevalent case diagnosed; number of contacts with LTBI that need to be treated
      with standard chemoprophylaxis to prevent 1 active case. RESULTS: Of 30 561
      contacts, 27 293 (89%) were evaluated and 268 prevalent cases were diagnosed (102
      contacts evaluated per prevalent case diagnosed, 95% confidence interval [CI], 90
      115). LTBI was diagnosed in 7597 contacts, including 6001 (79%) who initiated
      chemoprophylaxis, 3642 (61%) who later completed treatment, and 2359 (39%) who
      did not complete treatment. During 4 years of follow-up, active tuberculosis was
      diagnosed in 46 contacts with LTBI, including 22 of 6001 (0.4%) who initiated
      chemoprophylaxis and 24 of 1596 (1.5%) who did not initiate treatment. The
      absolute risk reduction afforded by chemoprophylaxis initiation was 1.1% (95% CI,
      .6%-1.9%), leading to an estimated 88 contacts treated to prevent 1 tuberculosis
      case (95% CI, 53-164). CONCLUSIONS: Contact investigation facilitates active case
      finding and tuberculosis prevention, even when completion rates of
      chemoprophylaxis are suboptimal.

PMID- 22412058
TI  - Changes in causes of acute gastroenteritis in the United Kingdom over 15 years:
      microbiologic findings from 2 prospective, population-based studies of infectious
      intestinal disease.
AB  - BACKGROUND: Large-scale, prospective studies of infectious intestinal disease
      (IID) in developed countries are uncommon. Two studies of IID incidence and
      etiology have been conducted in the United Kingdom: the Infectious Intestinal
      Disease Study in England (IID1) in 1993-1996 and the Second Study of Infectious
      Intestinal Disease in the Community (IID2) in 2008-2009. We examined changes in
      etiology and diagnostic yield of IID cases over 15 years. METHODS: Fecal samples
      submitted by IID cases were examined for a range of bacterial, viral, and
      protozoal pathogens using traditional and molecular microbiological methods. We
      calculated the percentage of specimens positive for each organism based on
      traditional methods and on traditional and molecular methods combined. We
      compared the distributions of organisms in the 2 studies. RESULTS: For pathogens
      investigated in both studies, 40% of fecal samples submitted by cases in IID2
      were positive compared with 28% in IID1. Viruses were most frequent among
      community cases in IID2. Campylobacter was the most common bacterial pathogen
      among cases presenting to healthcare. Major differences between the 2 studies
      were increases in the detection of norovirus and sapovirus and a decline
      Salmonella. CONCLUSIONS: Most fecal specimens were negative for the pathogens
      tested in both studies, so new strategies are needed to close the diagnostic gap.
      Among known pathogens, effective control of norovirus, rotavirus, and
      Campylobacter remain high priorities. The reduction in nontyphoidal salmonellosis
      demonstrates the success of Europe-wide control strategies, notably an industry
      led Salmonella control program in poultry in the United Kingdom.

PMID- 22412059
TI  - Epidemiology and outcomes of Clostridium difficile infections in hematopoietic
      stem cell transplant recipients.
AB  - Background. Clostridium difficile is the leading cause of infectious diarrhea
      among hospitalized patients and is a major concern for patients undergoing
      hematopoietic stem cell transplantation (HSCT). Risk factors and the natural
      history of C. difficile infection (CDI) are poorly understood in this population.
      Methods. We performed a retrospective nested case-control study to describe the
      epidemiology, timing, and risk factors for CDI among adult patients who received
      HSCTs at our center from January 2003 through December 2008. Results. The overall
      1-year incidence of CDI was 9.2% among HSCTs performed (n = 999). The median time
      to diagnosis of CDI was short among both autologous and allogeneic HSCT
      recipients (6.5 days and 33 days, respectively). Risk factors for CDI in
      allogeneic HSCT recipients included receipt of chemotherapy prior to conditioning
      for HSCT, broad-spectrum antimicrobial use, and acute graft-versus-host disease
      (GVHD; adjusted odds ratio [AOR], 4.45; 95% confidence interval [CI], 1.54-12.84;
      P = .006). There was a strong relationship between early CDI and subsequent
      development of gastrointestinal tract GVHD in the year following allogeneic HSCT
      (P < .001). Gastrointestinal GVHD was also strongly associated with an increased
      risk for recurrent CDI (AOR, 4.23 [95% CI, 1.20-14.86]; P = .02). Conclusions.
      These results highlight the high incidence and early timing of CDI after HSCT.
      Early timing, coupled with the noted risk of pretransplant chemotherapy, suggests
      that the natural history of disease in some patients may involve colonization
      prior to HSCT. A potentially important interplay between CDI and GVHD involving
      the gastrointestinal tract was observed.

PMID- 22412060
TI  - Interpreting quantitative cytomegalovirus DNA testing: understanding the
      laboratory perspective.
AB  - Cytomegalovirus (CMV) is an important cause of morbidity and mortality in
      transplant patients, and is typically monitored using laboratory-developed
      quantitative molecular assays. Clinicians who use quantitative CMV DNA testing
      should be aware of a number of aspects of testing that will aid in decision
      making while managing CMV disease in their patients. These include (1) the
      specimen type used (whole blood or plasma), (2) the limit of detection and limit
      of quantification chosen by the clinical laboratory, (3) the linear range of the
      assay, (4) the reproducibility of the assay within the institution, and (5) the
      wide variability of viral load values among different assays. The biologic
      properties of CMV, including its variability within the host and of its half
      life, are also important factors in the clinical testing for this virus.

PMID- 22412062
TI  - The end of an era in defining the optimal treatment of invasive candidiasis.

PMID- 22412061
TI  - Cost-effectiveness and population outcomes of general population screening for
      hepatitis C.
AB  - BACKGROUND: Current US guidelines recommend limiting hepatitis C virus (HCV)
      screening to high-risk individuals, and 50%-75% of infected persons remain
      unaware of their status. METHODS: To estimate the cost-effectiveness and
      population-level impact of adding one-time HCV screening of US population aged 20
      69 years to current guidelines, we developed a decision analytic model for the
      screening intervention and Markov model with annual transitions to estimate
      natural history. Subanalyses included protease inhibitor therapy and screening
      those at highest risk of infection (birth year 1945-1965). We relied on published
      literature and took a lifetime, societal perspective. RESULTS: Compared to
      current guidelines, incremental cost per quality-adjusted life year gained (ICER)
      was $7900 for general population screening and $4200 for screening by birth year,
      which dominated general population screening if cost, clinician uptake, and
      median age of diagnoses were assumed equivalent. General population screening
      remained cost-effective in all one-way sensitivity analyses, 30 000 Monte Carlo
      simulations, and scenarios in which background mortality was doubled, all
      genotype 1 patients were treated with protease inhibitors, and most parameters
      were set unfavorable to increased screening. ICER was lowest if screening was
      applied to a population with liver fibrosis similar to 2010 estimates.
      Approximately 1% of liver-related deaths would be averted per 15% of the general
      population screened; the impact would be greater with improved referral,
      treatment uptake, and cure. CONCLUSIONS: Broader screening for HCV would likely
      be cost-effective, but significantly reducing HCV-related morbidity and mortality
      would also require improved rates of referral, treatment, and cure.

PMID- 22412063
TI  - A randomized trial of the efficacy of hand disinfection for prevention of
      rhinovirus infection.
AB  - BACKGROUND: Hand disinfection is frequently recommended for prevention of
      rhinovirus (RV) infection and RV-associated common colds. The effectiveness of
      this intervention has not been established in a natural setting. The purpose of
      this study was to determine the effect of hand disinfection on RV infection and
      RV-associated common cold illness in a natural setting. METHODS: A controlled
      clinical trial was done in young adult volunteers during 9 weeks of the fall 2009
      RV season. Volunteers were randomized to either an antiviral hand treatment
      containing 2% citric acid and 2% malic acid in 62% ethanol (n = 116) or to a no
      treatment control group (n = 96). The hand treatment was applied every 3 hours
      while the subjects were awake. All volunteers kept a daily diary of symptoms and
      had a nasal lavage for polymerase chain reaction once each week and 2 additional
      lavages around the time of each common cold illness. The primary endpoint was the
      number of RV-associated illnesses. The incidence of RV infection and of common
      cold illnesses were evaluated as secondary endpoints. RESULTS: The hand treatment
      did not significantly reduce RV infection or RV-related common cold illnesses.
      The total number of common cold illnesses was significantly reduced in the intent
      to-treat analysis, but this effect was not seen in the per protocol analysis.
      CONCLUSIONS: In this study, hand disinfection did not reduce RV infection or RV
      related common cold illnesses. CLINICAL TRIALS REGISTRATION: NCT00993759.

PMID- 22412064
TI  - Chronic meningococcemia cutaneous lesions involve meningococcal perivascular
      invasion through the remodeling of endothelial barriers.
AB  - Chronic meningococcemia is a form of sepsis with frequent polymorphous skin
      lesions. Both in vivo and in vitro data suggest that, in these lesions,
      meningococci gain access from the capillary lumen to the peripheral extravascular
      compartment, in the absence of vascular dislocation, through a paraendothelial
      route.

PMID- 22412065
TI  - Need for long-term follow-up in enterohemorrhagic Escherichia coli-associated
      hemolytic uremic syndrome due to late-emerging sequelae.
AB  - BACKGROUND: The aim of this study was to evaluate the long-term prognosis of
      children with hemolytic uremic syndrome (HUS). METHODS: Over a 6-year period, 619
      pediatric patients with the clinical diagnosis of HUS were registered in Austria
      and Germany, and a subset (n = 274) was prospectively followed up for 5 years.
      RESULTS: Infection with enterohemorrhagic Escherichia coli (EHEC) was confirmed
      in 79% of cases. Five years after diagnosis, 70% of EHEC-infected patients (95%
      confidence interval [CI], .63-.76) were fully recovered. The remaining 30% had
      persistent hypertension (9%), neurological symptoms (4%), decreased glomerular
      filtration rate (7%), and/or proteinuria (18%). Hypertension and proteinuria
      developed in a total of 18% of patients who had no sequelae 1 year after the
      acute phase (95% CI, 12-26). Multivariate logistic regression analysis
      demonstrated an association between the use of plasma therapy during acute phase
      and poor long-term outcome (odds ratio, 2.9-13; 95% CI, 2.4-33; P < .05), but
      this treatment was also used more frequently in severe cases. In contrast, the
      use of antibiotic therapy in the diarrheal phase and other established risk
      factors for developing HUS, such as Shiga toxin 2 and EHEC serotypes
      traditionally considered to be "high risk," were not associated with adverse long
      term outcome. In particular, there was no difference between O157 and non-O157
      EHEC. CONCLUSIONS: This study identified an association between the use of plasma
      treatment and poor long-term outcome and confirms already known risk factors for
      poor prognosis. Follow-up investigations for at least 5 years are recommended to
      detect late-emerging sequelae.

PMID- 22412066
TI  - Dried blood spot specimens are a suitable alternative sample type for HIV-1 viral
      load measurement and drug resistance genotyping in patients receiving first-line
      antiretroviral therapy.
AB  - BACKGROUND: Antiretroviral therapy (ART) is being administered in developing
      nations at unprecedented numbers following the World Health Organization's (WHO)
      development of standardized first-line drug regimens. To ensure continued
      efficacy of these drug regimens, WHO recommends monitoring virological responses
      and development of human immunodeficiency virus (HIV) drug resistance (HIVDR) in
      HIV-infected patients in a prospective cohort. The current study compared dried
      fluid spot specimens with the reference standard plasma specimens as a practical
      tool for viral load (VL) and HIVDR genotyping in resource-limited settings.
      METHODS: Dried blood spot (DBS), dried plasma spot (DPS), and plasma specimens
      were collected from 173 -patients receiving ART at 2 hospital sites in Abuja,
      Nigeria. HIV-1 VL analysis was performed using NucliSENS EasyQ HIV-1 v1.1 RUO
      test kits. Genotyping of the HIV-1 pol gene was performed using a broadly
      sensitive in-house assay. RESULTS: Direct comparison of VL levels showed that DBS
      specimens, and not DPS specimens, gave results comparable to those of plasma
      specimens (P = .0619 and .0007, respectively); however, both DBS and DPS
      specimens had excellent correlation with plasma specimens in predicting
      virological failure (VL, >=1000 copies/mL) in patients (kappa = 0.78 and 0.83,
      respectively). Of the 18 specimens with a plasma VL >=1000 copies/mL, HIVDR
      genotyping rates were 100% in DBS and 38.9% in DPS specimens, and DBS specimens
      identified 61 of 65 HIVDR mutations (93.8%) identified in plasma specimens.
      CONCLUSIONS: Our results indicate that DBS specimens could be used for surveys to
      monitor HIVDR prevention failure in resource-limited settings.

PMID- 22412067
TI  - Predicting the clinical outcome of severe falciparum malaria in african children:
      findings from a large randomized trial.
AB  - BACKGROUND: Data from the largest randomized, controlled trial for the treatment
      of children hospitalized with severe malaria were used to identify such
      predictors of a poor outcome from severe malaria. METHODS: African children (<15
      years) with severe malaria participated in a randomized comparison of parenteral
      artesunate and parenteral quinine in 9 African countries. Detailed clinical
      assessment was performed on admission. Parasite densities were assessed in a
      reference laboratory. Predictors of death were examined using a multivariate
      logistic regression model. RESULTS: Twenty indicators of disease severity were
      assessed, out of which 5 (base deficit, impaired consciousness, convulsions,
      elevated blood urea, and underlying chronic illness) were associated
      independently with death. Tachypnea, respiratory distress, deep breathing, shock,
      prostration, low pH, hyperparasitemia, severe anemia, and jaundice were
      statistically significant indicators of death in the univariate analysis but not
      in the multivariate model. Age, glucose levels, axillary temperature, parasite
      density, heart rate, blood pressure, and blackwater fever were not related to
      death in univariate models. CONCLUSIONS: Acidosis, cerebral involvement, renal
      impairment, and chronic illness are key independent predictors for a poor outcome
      in African children with severe malaria. Mortality is markedly increased in
      cerebral malaria combined with acidosis. Clinical Trial Registration.
      ISRCTN50258054.

PMID- 22412068
TI  - Global longitudinal strain predicts long-term survival in patients with chronic
      ischemic cardiomyopathy.
AB  - BACKGROUND: Left ventricular (LV) global longitudinal strain (GLS) is a measure
      of the active shortening of the LV in the longitudinal direction, which can be
      assessed with speckle-tracking echocardiography. The aims of this evaluation were
      to validate the prognostic value of GLS as a new index of LV systolic function in
      a large cohort of patients with chronic ischemic cardiomyopathy and to determine
      the incremental value of GLS to predict long-term outcome over other strong and
      well-established prognostic factors. METHODS AND RESULTS: A total of 1060
      patients underwent baseline clinical evaluation and transthoracic
      echocardiography. Median age was 66.9 years (interquartile range, 58.4, 74.2
      years); 739 (70%) were men. The median follow-up duration for the entire patient
      population was 31 months. During the follow-up, 270 patients died and 309
      patients reached the combined end point (all-cause mortality and heart failure
      hospitalization). Compared with survivors, patients who died (270, [25%]) had
      larger LV volumes (P<0.05), lower LV ejection fraction (P=0.004), higher wall
      motion score index (P=0.001), and greater impairment of LV GLS (P<0.001). After
      dichotomizing the population on the basis of the median value of LV GLS (-11.5%),
      patients with an LV GLS <=-11.5% had superior outcome compared with patients with
      an LV GLS >-11.5% (log-rank chi(2), 13.86 and 14.16 for all-cause mortality and
      combined end point, respectively, P<0.001 for both). On multivariate analysis,
      GLS was independently related to all-cause mortality (hazard ratio per 5%
      increase, 1.69; 95% confidence interval, 1.33-2.15; P<0.001) and combined end
      point (1.64; 95% confidence interval, 1.32-2.04; P<0.001). CONCLUSIONS: The
      assessment of LV GLS with speckle-tracking echocardiography is significantly
      related to long-term outcome in patients with chronic ischemic cardiomyopathy.

PMID- 22412070
TI  - Sweetened beverage consumption, incident coronary heart disease, and biomarkers
      of risk in men.
AB  - BACKGROUND: Sugar-sweetened beverage consumption is associated with weight gain
      and risk of type 2 diabetes mellitus. Few studies have tested for a relationship
      with coronary heart disease (CHD) or intermediate biomarkers. The role of
      artificially sweetened beverages is also unclear. METHODS AND RESULTS: We
      performed an analysis of the Health Professionals Follow-Up Study, a prospective
      cohort study including 42 883 men. Associations of cumulatively averaged sugar
      sweetened (eg, sodas) and artificially sweetened (eg, diet sodas) beverage intake
      with incident fatal and nonfatal CHD (myocardial infarction) were examined with
      proportional hazard models. There were 3683 CHD cases over 22 years of follow-up.
      Participants in the top quartile of sugar-sweetened beverage intake had a 20%
      higher relative risk of CHD than those in the bottom quartile (relative
      risk=1.20; 95% confidence interval, 1.09-1.33; P for trend <0.01) after
      adjustment for age, smoking, physical activity, alcohol, multivitamins, family
      history, diet quality, energy intake, body mass index, pre-enrollment weight
      change, and dieting. Artificially sweetened beverage consumption was not
      significantly associated with CHD (multivariate relative risk=1.02; 95%
      confidence interval, 0.93-1.12; P for trend=0.28). Adjustment for self-reported
      high cholesterol, high triglycerides, high blood pressure, and diagnosed type 2
      diabetes mellitus slightly attenuated these associations. Intake of sugar
      sweetened but not artificially sweetened beverages was significantly associated
      with increased plasma triglycerides, C-reactive protein, interleukin-6, and tumor
      necrosis factor receptors 1 and 2 and decreased high-density lipoprotein,
      lipoprotein(a), and leptin (P<0.02). CONCLUSIONS: Consumption of sugar-sweetened
      beverages was associated with increased risk of CHD and some adverse changes in
      lipids, inflammatory factors, and leptin. Artificially sweetened beverage intake
      was not associated with CHD risk or biomarkers.

PMID- 22412071
TI  - Association or causation of sugar-sweetened beverages and coronary heart disease:
      recalling Sir Austin Bradford Hill.

PMID- 22412072
TI  - Conduction remodeling in human end-stage nonischemic left ventricular
      cardiomyopathy.
AB  - BACKGROUND: Several arrhythmogenic mechanisms have been inferred from animal
      heart failure models. However, the translation of these hypotheses is difficult
      because of the lack of functional human data. We aimed to investigate the
      electrophysiological substrate for arrhythmia in human end-stage nonischemic
      cardiomyopathy. METHODS AND RESULTS: We optically mapped the coronary-perfused
      left ventricular wedge preparations from human hearts with end-stage nonischemic
      cardiomyopathy (heart failure, n=10) and nonfailing hearts (NF, n=10). Molecular
      remodeling was studied with immunostaining, Western blotting, and histological
      analyses. Heart failure produced heterogeneous prolongation of action potential
      duration resulting in the decrease of transmural action potential duration
      dispersion (64 +/- 12 ms versus 129 +/- 15 ms in NF, P<0.005). In the failing
      hearts, transmural activation was significantly slowed from the endocardium (39
      +/- 3 cm/s versus 49 +/- 2 cm/s in NF, P=0.008) to the epicardium (28 +/- 3 cm/s
      versus 40 +/- 2 cm/s in NF, P=0.008). Conduction slowing was likely due to
      connexin 43 (Cx43) downregulation, decreased colocalization of Cx43 with N
      cadherin (40 +/- 2% versus 52 +/- 5% in NF, P=0.02), and an altered distribution
      of phosphorylated Cx43 isoforms by the upregulation of the dephosphorylated Cx43
      in both the subendocardium and subepicardium layers. Failing hearts further
      demonstrated spatially discordant conduction velocity alternans which resulted in
      nonuniform propagation discontinuities and wave breaks conditioned by strands of
      increased interstitial fibrosis (fibrous tissue content in heart failure 16.4 +/-
      7.7 versus 9.9 +/- 1.4% in NF, P=0.02). CONCLUSIONS: Conduction disorder
      resulting from the anisotropic downregulation of Cx43 expression, the reduction
      of Cx43 phosphorylation, and increased fibrosis is likely to be a critical
      component of arrhythmogenic substrate in patients with nonischemic
      cardiomyopathy.

PMID- 22412073
TI  - Obesity treatment for socioeconomically disadvantaged patients in primary care
      practice.
AB  - BACKGROUND: Few evidence-based weight loss treatment options exist for medically
      vulnerable patients in the primary care setting. METHODS: We conducted a 2-arm,
      24-month randomized effectiveness trial in 3 Boston community health centers
      (from February 1, 2008, through May 2, 2011). Participants were 365 obese
      patients receiving hypertension treatment (71.2% black, 13.1% Hispanic, 68.5%
      female, and 32.9% with less than a high school educational level). We randomized
      participants to usual care or a behavioral intervention that promoted weight loss
      and hypertension self-management using eHealth components. The intervention
      included tailored behavior change goals, self-monitoring, and skills training,
      available via a website or interactive voice response; 18 telephone counseling
      calls; primary care provider endorsement; 12 optional group support sessions; and
      links with community resources. RESULTS: At 24 months, weight change in the
      intervention group compared with that in the usual care group was -1.03 kg (95%
      CI, -2.03 to -0.03 kg). Twenty-four-month change in body mass index (calculated
      as weight in kilograms divided by height in meters squared) in the intervention
      group compared with that in the usual care group was -0.38 (95% CI, -0.75 to 
      0.004). Intervention participants had larger mean weight losses during the 24
      months compared with that in the usual care group (area under the receiver
      operating characteristic curve, -1.07 kg; 95% CI, -1.94 to -0.22). Mean systolic
      blood pressure was not significantly lower in the intervention arm compared with
      the usual care arm. CONCLUSION: The intervention produced modest weight losses,
      improved blood pressure control, and slowed systolic blood pressure increases in
      this high-risk, socioeconomically disadvantaged patient population. Trial
      Registration  clinicaltrials.gov Identifier: NCT00661817.

PMID- 22412074
TI  - The role of care coordinators in improving care coordination: the patient's
      perspective.

PMID- 22412076
TI  - Intensive care unit bed availability and outcomes for hospitalized patients with
      sudden clinical deterioration.
AB  - BACKGROUND: Intensive care unit (ICU) beds, a scarce resource, may require
      prioritization of admissions when demand exceeds supply. We evaluated the effect
      of ICU bed availability on processes and outcomes of care for hospitalized
      patients with sudden clinical deterioration. METHODS: We identified consecutive
      hospitalized adults in Calgary, Alberta, Canada, with sudden clinical
      deterioration triggering medical emergency team activation between January 1,
      2007, and December 31, 2009. We compared ICU admission rates (within 2 hours of
      medical emergency team activation), patient goals of care (resuscitative,
      medical, and comfort), and hospital mortality according to the number of ICU beds
      available (0, 1, 2, or >2), adjusting for patient, physician, and hospital
      characteristics (using data from clinical and administrative databases). RESULTS:
      The cohort consisted of 3494 patients. Reduced ICU bed availability was
      associated with a decreased likelihood of patient admission within 2 hours of
      medical emergency team activation (P = .03) and with an increased likelihood of
      change in patient goals of care (P < .01). Patients with sudden clinical
      deterioration when zero ICU beds were available were 33.0% (95% CI, -5.1% to
      57.3%) less likely to be admitted to the ICU and 89.6% (95% CI, 24.9% to 188.0%)
      more likely to have their goals of care changed compared with when more than 2
      ICU beds were available. Hospital mortality did not vary significantly by ICU bed
      availability (P = .82). CONCLUSION: Among hospitalized patients with sudden
      clinical deterioration, we noted a significant association between the number of
      ICU beds available and ICU admission and patient goals of care but not hospital
      mortality.

PMID- 22412075
TI  - Red meat consumption and mortality: results from 2 prospective cohort studies.
AB  - BACKGROUND: Red meat consumption has been associated with an increased risk of
      chronic diseases. However, its relationship with mortality remains uncertain.
      METHODS: We prospectively observed 37 698 men from the Health Professionals
      Follow-up Study (1986-2008) and 83 644 women from the Nurses' Health Study (1980
      2008) who were free of cardiovascular disease (CVD) and cancer at baseline. Diet
      was assessed by validated food frequency questionnaires and updated every 4
      years. RESULTS: We documented 23 926 deaths (including 5910 CVD and 9464 cancer
      deaths) during 2.96 million person-years of follow-up. After multivariate
      adjustment for major lifestyle and dietary risk factors, the pooled hazard ratio
      (HR) (95% CI) of total mortality for a 1-serving-per-day increase was 1.13 (1.07
      1.20) for unprocessed red meat and 1.20 (1.15-1.24) for processed red meat. The
      corresponding HRs (95% CIs) were 1.18 (1.13-1.23) and 1.21 (1.13-1.31) for CVD
      mortality and 1.10 (1.06-1.14) and 1.16 (1.09-1.23) for cancer mortality. We
      estimated that substitutions of 1 serving per day of other foods (including fish,
      poultry, nuts, legumes, low-fat dairy, and whole grains) for 1 serving per day of
      red meat were associated with a 7% to 19% lower mortality risk. We also estimated
      that 9.3% of deaths in men and 7.6% in women in these cohorts could be prevented
      at the end of follow-up if all the individuals consumed fewer than 0.5 servings
      per day (approximately 42 g/d) of red meat. CONCLUSIONS: Red meat consumption is
      associated with an increased risk of total, CVD, and cancer mortality.
      Substitution of other healthy protein sources for red meat is associated with a
      lower mortality risk.

PMID- 22412077
TI  - Deferred admission to the intensive care unit: rationing critical care or
      expediting care transitions?

PMID- 22412078
TI  - Holy Cow! What's good for you is good for our planet: comment on "Red Meat
      Consumption and Mortality".

PMID- 22412079
TI  - Changing the lexicon of 'Cardiac Rehabilitation': a progressive step.

PMID- 22412081
TI  - A periodized model for exercise improves the intra-hospital evolution of patients
      after myocardial revascularization: a pilot randomized controlled trial.
AB  - OBJECTIVE: To compare models of the postoperative hospital treatment phase after
      myocardial revascularization. DESIGN: A pilot randomized controlled trial.
      SETTING: Hospital patients in a hospital setting. SUBJECTS: Thirty-two patients
      with indications for myocardial revascularization were included between January
      2008 and December 2009, with a left ventricular ejection fraction (LVEF) >=50%, 1
      second forced expiratory volume (FEV(1)) >=60 and forced vital capacity (FVC)
      >=60% of predicted value. INTERVENTIONS: Patients were randomly placed into two
      groups: one performed prescribed exercises according to the model proposed by the
      American College of Sports Medicine (ACSM) and the other according to a
      periodized model. MAIN MEASURES: Partial pressure of O(2) (P o (2)) and arterial
      O(2) saturation (Sao (2)), percentage of predicted FVC and total distance on the
      six-minute walking test (6MWT). RESULTS: Twenty-seven patients were re-evaluated
      upon release from the hospital (ACSM = 14 and PP = 13). Five patients extubated
      for more than 6 hours in the postoperative period were excluded from the sample.
      In the preoperative period the variables P o (2), Sao (2), % FVC and 6MWT were
      similar. In the postoperative period, a reduction was observed for all parameters
      in both groups. Upon comparison of the groups, a difference was observed in P o
      (2) (ACSM = 68.0 +/- 4.3 vs. PP = 75.9 +/- 4.8 mmHg; P < 0.001), Sao (2) (ACSM =
      93.5 +/- 1.4 vs. PP = 94.8 +/- 1.2%; P = 0.018) and 6MWT (ACSM = 339.3 +/- 41.7
      vs. PP = 393.8 +/- 25.7 m; P < 0.001). There was no difference in % FVC.
      CONCLUSION: Patients after myocardial revascularization following a periodized
      model of exercise presented a better intra-hospital evolution when compared to
      those using the ACSM model.

PMID- 22412082
TI  - The differential effects of gratitude and sleep on psychological distress in
      patients with chronic pain.
AB  - This study aimed to examine the possible cross-sectional mediating role of sleep
      in the relationship of gratitude with depression and anxiety in patients with
      chronic pain. A total of 224 patients with chronic pain completed structured
      questionnaires assessing chronic pain, depression and anxiety symptoms,
      gratitude, and sleep disturbances. Results of multiple regression analyses
      yielded a modest mediating effect for sleep on the gratitude-depression link
      whereas a stronger mediating effect was found for sleep on the gratitude-anxiety
      link. These data show much of the effect of gratitude on depression was direct
      whereas sleep exerted a stronger mediating effect on the gratitude-anxiety link.

PMID- 22412083
TI  - Safety issues on British mental health wards.
AB  - BACKGROUND: Assuring patient safety on inpatient psychiatric units is a complex
      issue that involves mitigating risks as well as promoting safety by building an
      environment that supports engagement and constructive activity. OBJECTIVES: To
      review the concerns surrounding inpatient psychiatric units in the United Kingdom
      that led to a service user-designed program, Star Wards. The essential elements
      of the program are outlined along with a rationale for how Star Wards' 75 ideas
      effectively build greater engagement, address boredom, and enhance safety on
      inpatient psychiatric wards. DESIGN: This article reports on the development and
      dissemination of Star Wards. Included is information on the program's
      effectiveness; data were drawn from an evaluation of Star Wards conducted by a
      U.K. university. RESULTS: Psychiatric wards that have adopted Star Wards have
      demonstrated improvements in patient satisfaction, staff morale, levels of
      boredom, and incidents of aggression. CONCLUSION: Boredom and poor staff-patient
      engagement on psychiatric wards may contribute to aggression and violence.
      Drawing on Star Wards ideas, nurses and service users can work together to
      enhance safety via an active ward program and greater staff-patient engagement.
      The innovations suggested by Star Wards are practical ways to build programming
      and create platforms for dialogue with service users, particularly around what
      they need to move toward recovery.

PMID- 22412084
TI  - Registered nurses' and behavior health associates' responses to violent inpatient
      interactions on behavioral health units.
AB  - BACKGROUND: Violence carried out by patients against nursing staff unsettles and
      threatens coworkers as they care for individuals admitted to inpatient
      psychiatric units. OBJECTIVE: This study explored nursing staff's individual and
      group responses to violent incidents performed by patients against caregivers.
      DESIGN: This qualitative study used focus groups to collect data from
      professional nurses and behavioral health associations (N = 19) recruited from
      urban, inpatient psychiatric unit. Data were analyzed thematically. RESULTS:
      Sharing information about violence, intervening therapeutically, intervening
      nontherapeutically, recognizing team influences, experiencing emotions following
      violence, and understanding the work environment comprised the major themes of
      the experience. CONCLUSIONS: Findings may stimulate discussions and education
      sessions that address strategies helpful to nursing staff so that incidents are
      prevented and staff is supported following such disturbing events. Events of
      workplace violence, including those occurring on behavioral mental health in
      inpatient units, require accurate individual and aggregate reporting to develop
      interventions and evaluate effectiveness of violence reduction strategies.

PMID- 22412085
TI  - Developing patient-centered treatment protocols in brain stimulation: a rationale
      for combining quantitative and qualitative approaches in persons with HIV.
AB  - This article reports and discusses how quantitative (physiological and
      behavioral) and qualitative methods are being combined in an open-label pilot
      feasibility study. The study evaluates safety, tolerability, and acceptability of
      a protocol to treat depression in HIV-infected individuals, using a 2-week block
      of transcranial direct current stimulation (tDCS) over the dorsolateral
      prefrontal cortex. Major depressive disorder (MDD) is the second most prevalent
      psychiatric disorder after substance abuse among HIV-positive adults, and novel
      antidepressant treatments are needed for this vulnerable population. The authors
      describe the challenges and contributions derived from different research
      perspectives and methodological approaches and provide a philosophical framework
      for combining quantitative and qualitative measurements for a fuller examination
      of the disorder. Four methodological points are presented: (1) the value of
      combining quantitative and qualitative approaches; (2) the need for context
      specific measures when studying patients with medical and psychiatric
      comorbidities; (3) the importance of research designs that integrate
      physiological, behavioral, and qualitative approaches when evaluating novel
      treatments; and (4) the need to explore the relationships between biomarkers,
      clinical symptom assessments, patient self-evaluations, and patient experiences
      when developing new, patient-centered protocols. The authors conclude that the
      complexity of studying novel treatments in complex and new patient populations
      requires complex research designs to capture the richness of data that inform
      translational research.

PMID- 22412087
TI  - Irreproducible experimental results: causes, (mis)interpretations, and
      consequences.

PMID- 22412086
TI  - High-throughput luciferase reporter assay for small-molecule inhibitors of
      microRNA function.
AB  - MicroRNAs (miRNAs) are endogenous, single-stranded, noncoding RNAs of 21 to 23
      nucleotides that regulate gene expression, typically by binding the 3'
      untranslated regions of target messenger RNAs. It is estimated that miRNAs are
      involved in the regulation of 30% of all genes and almost every genetic pathway.
      Recently, the misregulation of miRNAs has been linked to various human diseases
      including cancer and viral infections, identifying miRNAs as potential targets
      for drug discovery. Thus, small-molecule modifiers of miRNAs could serve as lead
      structures for the development of new therapeutic agents and be useful tools in
      the elucidation of detailed mechanisms of miRNA function. As a result, we have
      developed a high-throughput screen for potential small-molecule regulators of the
      liver-specific microRNA miR-122, which is involved in hepatocellular carcinoma
      development and hepatitis C virus infection. Our small-molecule screen employs a
      Huh7 human hepatoma cell line stably transfected with a Renilla luciferase sensor
      for endogenous miR-122. The assay was optimized and validated using an miR-122
      antisense agent and a previously identified small-molecule miR-122 inhibitor. The
      described reporter assay will enable the high-throughput screening of small
      molecule miR-122 inhibitors and can be readily extended to other miRNAs.

PMID- 22412088
TI  - Epoxyeicosatrienoic acids contribute with altered nitric oxide and endothelin-1
      pathways to conduit artery endothelial dysfunction in essential hypertension.
AB  - BACKGROUND: We sought to clarify, using functional and biological approaches, the
      role of epoxyeicosatrienoic acids, nitric oxide (NO)/reactive oxygen species
      balance, and endothelin-1 in conduit artery endothelial dysfunction during
      essential hypertension. METHODS AND RESULTS: Radial artery diameter and mean wall
      shear stress were determined in 28 untreated patients with essential hypertension
      and 30 normotensive control subjects during endothelium-dependent flow-mediated
      dilatation induced by hand skin heating. The role of epoxyeicosatrienoic acids
      and NO was assessed with the brachial infusion of inhibitors of cytochrome P450
      epoxygenases (fluconazole) and NO synthase (N(G)-monomethyl-l-arginine [L-NMMA]).
      Compared with controls, hypertensive patients exhibited a decreased flow-mediated
      dilatation in response to postischemic hyperemia as well as to heating, as shown
      by the lesser slope of their diameter-shear stress relationship. In controls,
      heating-induced flow-mediated dilatation was reduced by fluconazole, L-NMMA, and,
      to a larger extent, by L-NMMA+fluconazole. In patients, flow-mediated dilatation
      was not affected by fluconazole and was reduced by L-NMMA and L-NMMA+fluconazole
      to a lesser extent than in controls. Furthermore, local plasma
      epoxyeicosatrienoic acids increased during heating in controls (an effect
      diminished by fluconazole) but not in patients. Plasma nitrite, an indicator of
      NO availability, increased during heating in controls (an effect abolished by L
      NMMA) and, to a lesser extent, in patients, whereas, inversely, reactive oxygen
      species increased more in patients (an effect diminished by L-NMMA). Plasma
      endothelin-1 decreased during heating in controls but not in patients.
      CONCLUSIONS: These results show that an impaired role of epoxyeicosatrienoic
      acids contributes, together with an alteration in NO/reactive oxygen species
      balance and endothelin-1 pathway, to conduit artery endothelial dysfunction in
      essential hypertension. CLINICAL TRIAL REGISTRATION:
      https://www.eudract.ema.europa.eu. Unique identifier: RCB2007-A001-10-53.

PMID- 22412089
TI  - Do platelet function testing and genotyping improve outcome in patients treated
      with antithrombotic agents?: platelet function testing and genotyping improve
      outcome in patients treated with antithrombotic agents.

PMID- 22412090
TI  - Do platelet function testing and genotyping improve outcome in patients treated
      with antithrombotic agents?: the role of platelet reactivity and genotype testing
      in the prevention of atherothrombotic cardiovascular events remains unproven.

PMID- 22412091
TI  - Mechanical circulatory support for advanced heart failure: patients and
      technology in evolution.

PMID- 22412092
TI  - A rare complication of infective endocarditis.

PMID- 22412093
TI  - Amplatzer device deployment for saccular aortic arch aneurysm: a note of caution.

PMID- 22412095
TI  - Two cases of calcified amorphous tumor mimicking mitral valve vegetation.

PMID- 22412096
TI  - Recurrent ventricular tachycardia in malignant metastatic pheochromocytoma.

PMID- 22412097
TI  - Cardiology patient page: Aspirin.

PMID- 22412099
TI  - Letter by Weingartner et al regarding article, "Combined effects of ezetimibe and
      phytosterols on cholesterol metabolism: a randomized, controlled feeding study in
      humans".

PMID- 22412100
TI  - Letter by Perez de Prado et al regarding article, "Delayed coverage in malapposed
      and side-branch struts with respect to well-apposed struts in drug-eluting
      stents: in vivo assessment with optical coherence tomography".

PMID- 22412101
TI  - Letter by Mehran et al regarding article, "Bleeding academic research consortium
      consensus report: the food and drug administration perspective".

PMID- 22412103
TI  - Significance of ST-segment elevation in lead aVR.

PMID- 22412105
TI  - Consequences of not respecting patient preferences for cancer screening:
      opportunity lost.

PMID- 22412106
TI  - Long-term analgesic use after low-risk surgery: a retrospective cohort study.
AB  - BACKGROUND: This study evaluated the risk of long-term analgesic use after low
      risk surgery in older adults not previously prescribed analgesics. METHODS: We
      conducted a retrospective cohort study using linked, population-based
      administrative data in Ontario, Canada, from April 1, 1997, through December 31,
      2008. We identified Ontario residents 66 years and older who were dispensed an
      opioid within 7 days of a short-stay surgery (cataract surgery, laparoscopic
      cholecystectomy, transurethral resection of the prostate, or varicose vein
      stripping) and assessed the risk of long-term opioid use, defined as a
      prescription for an opioid within 60 days of the 1-year anniversary of the
      surgery. In a secondary analysis, we examined the risk of long-term use of
      nonsteroidal anti-inflammatory drugs (NSAIDs). We used multivariate logistic
      regression to examine the association between postsurgical use of analgesics and
      long-term use. RESULTS: Among 391,139 opioid-naive patients undergoing short-stay
      surgery, opioids were newly prescribed to 27,636 patients (7.1%) within 7 days of
      being discharged from the hospital, and opioids were prescribed to 30,145
      patients (7.7%) at 1 year from surgery. An increase in the use of oxycodone was
      found during this time (from 5.4% within 7 days to 15.9% at 1 year). In our
      primary analysis, patients receiving an opioid prescription within 7 days of
      surgery were 44% more likely to become long-term opioid users within 1 year
      compared with those who received no such prescription (adjusted odds ratio, 1.44;
      95% CI, 1.39-1.50). In a secondary analysis, among 383,780 NSAID-naive patients
      undergoing short-stay surgery, NSAIDs were prescribed to 1169 patients (0.3%)
      within 7 days of discharge and to 30,080 patients (7.8%) at 1 year from surgery.
      Patients who began taking NSAIDs within 7 days of surgery were almost 4 times
      more likely to become long-term NSAID users compared with patients with no such
      prescription (adjusted odds ratio, 3.74; 95% CI, 3.27-4.28). CONCLUSION:
      Prescription of analgesics immediately after ambulatory surgery occurs frequently
      in older adults and is associated with long-term use.

PMID- 22412107
TI  - Harm from long-term opioid therapy: comment on "Long-term analgesic use after low
      risk surgery".

PMID- 22412108
TI  - Sex differences in long-term opioid use: cautionary notes for prescribing in
      women.

PMID- 22412109
TI  - What are we treating with long-term opioid therapy?

PMID- 22412110
TI  - Impact of mobile tablet computers on internal medicine resident efficiency.

PMID- 22412111
TI  - Mobile tablets: benefits to residents and patients.

PMID- 22412112
TI  - Smoking cessation, weight gain, and risk of type 2 diabetes mellitus among
      postmenopausal women.

PMID- 22412113
TI  - Obesity and increased risk for oligozoospermia and azoospermia.

PMID- 22412114
TI  - Effect of antihypertensive therapy on cognitive function in early executive
      cognitive impairment: a double-blind randomized clinical trial.

PMID- 22412115
TI  - Total daily physical activity and longevity in old age.

PMID- 22412116
TI  - Screening mammograms should not be underestimated.

PMID- 22412117
TI  - The debate over lifesaving benefit of screening mammography continues.

PMID- 22412118
TI  - Screen detection has both winners and losers.

PMID- 22412119
TI  - Dietary supplements and mortality.

PMID- 22412120
TI  - Dietary supplements and altered mortality: a conflict of evolutionary medicine.

PMID- 22412121
TI  - The importance of translating research skillfully to benefit the public.

PMID- 22412122
TI  - Is it possible to identify clinically useful prognostic groups for patients with
      desmoid tumors?

PMID- 22412124
TI  - Psychosocial care for family caregivers of patients with cancer.
AB  - PURPOSE: To understand family caregivers' needs for better preparation and care,
      this state-of-the-science review examines the effect of caregiving on the health
      and well-being of caregivers, the efficacy of research-tested interventions on
      patient and caregiver outcomes, implications of the research on policy and
      practice, and recommendations for practice and future research. METHODS: We
      reviewed research that described the multiple effects of cancer on caregivers'
      well-being. Five meta-analyses were analyzed to determine the effect of
      interventions with caregivers on patient and caregiver outcomes. In addition, we
      reviewed legislation such as the Affordable Care Act and the Family Leave Act
      along with current primary care practice to determine whether family caregivers'
      needs have been addressed. RESULTS: Research findings indicate that caregiver
      stress can lead to psychological and sleep disturbances and changes in
      caregivers' physical health, immune function, and financial well-being. Research
      tested interventions delivered to caregivers of patients with cancer or other
      chronic illnesses can reduce many of these negative effects and improve
      caregivers' coping skills, knowledge, and quality of life. Although these
      interventions also decrease patients' symptoms, reduce mortality (non-dementia
      patients), and improve patients' physical and mental health, they are seldom
      implemented in practice. CONCLUSION: Recommendations for practice include
      development of standardized guidelines that address caregiver assessment,
      education, and resources; identification of "caregiver champions" in practice
      settings; provision of referrals to established support organizations for
      caregivers (eg, Cancer Support Community, Cancer Care); and collaboration among
      caregiving, professional, and cancer-related organizations to advocate policy and
      practice changes for family caregivers.

PMID- 22412123
TI  - Evidence-based treatment of delirium in patients with cancer.
AB  - Delirium is the most common neuropsychiatric complication seen in patients with
      cancer, and it is associated with significant morbidity and mortality. Increased
      health care costs, prolonged hospital stays, and long-term cognitive decline are
      other well-recognized adverse outcomes of delirium. Improved recognition of
      delirium and early treatment are important in diminishing such morbidity. There
      has been an increasing number of studies published in the literature over the
      last 10 years regarding delirium treatment as well as prevention. Antipsychotics,
      cholinesterase inhibitors, and alpha-2 agonists are the three groups of
      medications that have been studied in randomized controlled trials in different
      patient populations. In patients with cancer, the evidence is most clearly
      supportive of short-term, low-dose use of antipsychotics for controlling the
      symptoms of delirium, with close monitoring for possible adverse effects,
      especially in older patients with multiple medical comorbidities.
      Nonpharmacologic interventions also appear to have a beneficial role in the
      treatment of patients with cancer who have or are at risk for delirium. This
      article presents evidence-based recommendations based on the results of
      pharmacologic and nonpharmacologic studies of the treatment and prevention of
      delirium.

PMID- 22412125
TI  - Caring for the whole patient: the science of psychosocial care.

PMID- 22412126
TI  - Palliative sedation: when and how?

PMID- 22412127
TI  - Role of radiation therapy in the management of locally advanced pancreatic
      cancer.

PMID- 22412128
TI  - Identifying early melanomas at higher risk for metastases.

PMID- 22412129
TI  - Palliative sedation in end-of-life care and survival: a systematic review.
AB  - PURPOSE: Palliative sedation is a clinical procedure aimed at relieving
      refractory symptoms in patients with advanced cancer. It has been suggested that
      sedative drugs may shorten life, but few studies exist comparing the survival of
      sedated and nonsedated patients. We present a systematic review of literature on
      the clinical practice of palliative sedation to assess the effect, if any, on
      survival. METHODS: A systematic review of literature published between January
      1980 and December 2010 was performed using MEDLINE and EMBASE databases. Search
      terms included palliative sedation, terminal sedation, refractory symptoms,
      cancer, neoplasm, palliative care, terminally ill, end-of-life care, and
      survival. A manual search of the bibliographies of electronically identified
      articles was also performed. RESULTS: Eleven published articles were identified
      describing 1,807 consecutive patients in 10 retrospective or prospective
      nonrandomized studies, 621 (34.4%) of whom were sedated. One case-control study
      was excluded from prevalence analysis. The most frequent reason for sedation was
      delirium in the terminal stages of illness (median, 57.1%; range, 13.8% to
      91.3%). Benzodiazepines were the most common drug category prescribed. Comparing
      survival of sedated and nonsedated patients, the sedation approach was not shown
      to be associated with worse survival. CONCLUSION: Even if there is no direct
      evidence from randomized clinical trials, palliative sedation, when appropriately
      indicated and correctly used to relieve unbearable suffering, does not seem to
      have any detrimental effect on survival of patients with terminal cancer. In this
      setting, palliative sedation is a medical intervention that must be considered as
      part of a continuum of palliative care.

PMID- 22412130
TI  - Radiotherapy improves survival in unresectable pancreatic cancer: small trial but
      big (and credible) results.

PMID- 22412131
TI  - Preoperative identification of a low-risk group for lymph node metastasis in
      endometrial cancer: a Korean gynecologic oncology group study.
AB  - PURPOSE: The aim of this study was to develop a preoperative risk prediction
      model for lymph node metastasis in patients with endometrial cancer and to
      identify a low-risk group before surgery. PATIENTS AND METHODS: The medical
      records of 360 patients with endometrial cancer who underwent surgical staging
      were collected from four institutions and were retrospectively reviewed. By using
      serum CA-125 levels, preoperative biopsy data, and magnetic resonance imaging
      (MRI) data, a multivariate logistic model was created. Patients whose predicted
      probability was less than 4% were defined as low risk. The developed model was
      externally validated in 180 patients from two independent institutions. RESULTS:
      Serum CA-125 levels and three MRI parameters (deep myometrial invasion, lymph
      node enlargement, and extension beyond uterine corpus) were found to be
      independent risk factors for nodal metastasis. The model classified 53% of
      patients as part of a low-risk group, and the false negative rate was 1.7%. In
      the validation cohort, the model classified 43% of patients as low-risk, and the
      false negative rate was 1.4%. The model showed good discrimination (area under
      the receiver operator characteristic curve = 0.85) and was calibrated well. The
      negative likelihood ratio of our low-risk criteria was 0.11 (95% CI, 0.04 to
      0.29), which was equivalent to the false-negative rate of 1.3% (95% CI, 0.5% to
      3.3%) at the assumed prevalence of nodal metastasis of 10%. CONCLUSION: Using
      serum CA-125 and MRI as criteria resulted in the accurate identification of a low
      risk group for lymph node metastasis among patients with endometrial cancer.

PMID- 22412132
TI  - Neoadjuvant chemotherapy is rarely the easy way out.

PMID- 22412133
TI  - What happens now? Psychosocial care for cancer survivors after medical treatment
      completion.
AB  - The growing population of adults living with a history of cancer in the United
      States mandates attention to quality of life and health in this group, as well as
      to the implementation of evidence-based interventions to address psychosocial and
      physical concerns at completion of medical treatments and beyond. The goals of
      this article are to document the need for attention to psychosocial domains
      during the re-entry and later phases of the cancer survivor trajectory, offer an
      overview of current evidence on efficacy of psychosocial interventions during
      those phases, and offer suggestions for application and research regarding post
      treatment psychosocial care.

PMID- 22412134
TI  - A new quality standard: the integration of psychosocial care into routine cancer
      care.
AB  - There is a growing consensus that psychosocial care should be integrated into the
      routine care of patients with cancer. This consensus is consistent with the
      considerable body of evidence about the deleterious effects of allowing
      psychosocial needs to remain unmet and the growing body of evidence about the
      beneficial effects of providing psychosocial services to address unmet needs.
      Despite this evidence, available data suggest that a considerable portion of the
      population of patients with cancer does not receive needed psychosocial care.
      Three lines of professional activity initiated in recent years have the potential
      to address this issue in fundamental ways: the formulation of standards of cancer
      care that address the psychosocial component of care, the issuance of clinical
      practice guidelines for psychosocial care of patients with cancer, and the
      development and implementation of measurable indicators of the quality of
      psychosocial care in oncology settings. This article provides an overview of
      accomplishments in each of these areas; it is designed to ensure that oncologists
      and other cancer treatment providers are knowledgeable about current standards
      for psychosocial care, existing consensus- and evidenced-based recommendations
      for clinical practice in this area, and resources and tools for evaluating and,
      if indicated, improving the quality of the psychosocial care their patients are
      receiving. The article concludes with a critical appraisal of these activities
      and a consideration of how current efforts might be enhanced.

PMID- 22412135
TI  - Evidence-based treatment of anxiety in patients with cancer.
AB  - Anxiety is a dynamic response to perceived threat that is common among patients
      with cancer and fluctuates at critical points in the disease trajectory. A
      substantial minority of patients may experience clinically significant anxiety
      resulting from a range of potential etiologic factors. This review summarizes
      evidence-based recommendations for treatment of anxiety in oncology settings.
      Recommendations are based on the nature and time course of anxiety and the
      results of meta-analyses, systematic reviews, and individual trials in cancer
      populations. The evidence-based literature supports the use of psychosocial and
      psychopharmacologic treatments to prevent or alleviate anxiety symptoms.
      CONCLUSIONS: are tempered by study heterogeneity and methodologic limitations and
      a lack of trials that included patients with clinically significant anxiety. In
      oncology settings, accessibility and acceptability of evidence-based treatments
      vary, and patients may seek a variety of resources to manage cancer concerns.
      Treatment planning should incorporate contributing factors to anxiety and patient
      preferences for psychiatric care.

PMID- 22412136
TI  - Risk factors for financial hardship in patients receiving adjuvant chemotherapy
      for colon cancer: a population-based exploratory analysis.
AB  - PURPOSE: Characteristics that predispose patients to financial hardship during
      cancer treatment are poorly understood. We therefore conducted a population-based
      exploratory analysis of potential factors associated with financial hardship and
      treatment nonadherence during and following adjuvant chemotherapy for colon
      cancer. PATIENTS AND METHODS: Patients diagnosed with stage III colon cancer
      between 2008 and 2010 were identified from a population-based cancer registry
      representing 13 counties in Washington state. Patients were asked to complete a
      comprehensive survey on treatment-related costs. Patients were considered to have
      experienced financial hardship if they accrued debt, sold or refinanced their
      home, borrowed money from friends or family, or experienced a 20% or greater
      decline in their annual income as a result of treatment-related expenses.
      Logistic regression analysis was used to investigate factors associated with
      financial hardship and treatment nonadherence. RESULTS: A total of 284 responses
      were obtained from 555 eligible patients (response rate, 51.2%). Nearly all
      patients in the final sample were insured during treatment. In this sample, 38%
      of patients reported one or more financial hardships as a result of treatment.
      The factors most closely associated with treatment-related financial hardship
      were younger age and lower annual household income. Younger age, lower income,
      and unemployment or disability (which occurred in most instances following
      diagnosis) were most closely associated with treatment nonadherence. CONCLUSION:
      A significant proportion of patients undergoing adjuvant chemotherapy for stage
      III colon cancer may experience financial hardship, despite having health
      insurance coverage. Interventions to help at-risk patients early on during
      therapy may prevent long-term financial adverse effects.

PMID- 22412137
TI  - Dual blockade of epidermal growth factor receptor-induced pathways: a new avenue
      to treat metastatic colorectal cancer.

PMID- 22412138
TI  - Oncologist burnout: causes, consequences, and responses.
AB  - Although the practice of oncology can be extremely rewarding, it is also one of
      the most demanding and stressful areas of medicine. Oncologists are faced with
      life and death decisions on a daily basis, administer incredibly toxic therapies
      with narrow therapeutic windows, must keep up with the rapid pace of scientific
      and treatment advances, and continually walk a fine line between providing
      palliation and administering treatments that lead to excess toxicity. Personal
      distress precipitated by such work-related stress may manifest in a variety of
      ways including depression, anxiety, fatigue, and low mental quality of life.
      Burnout also seems to be one of the most common manifestations of distress among
      physicians, with studies suggesting a prevalence of 35% among medical
      oncologists, 38% among radiation oncologists, and 28% to 36% among surgical
      oncologists. Substantial evidence suggests that burnout can impact quality of
      care in a variety of ways and has potentially profound personal implications for
      physicians including suicidal ideation. In this review, we examine the causes,
      consequences, and personal ramifications of oncologist burnout and explore the
      steps oncologists can take to promote personal well-being and professional
      satisfaction.

PMID- 22412139
TI  - Integrating psychosocial care into cancer services.
AB  - Despite substantial evidence that patients with cancer commonly have significant
      psychosocial problems, for which we have evidence-based treatments, many patients
      still do not receive adequate psychosocial care. This means that we risk
      prolonging life without adequately addressing the quality of that life. There are
      many challenges to improving the current situation, the major one of which is
      organizational. Many cancer centers lack a system of psychosocial care that is
      integrated with the cancer care of the patient. Psychosocial care encompasses a
      range of problems (emotional, social, palliative, and logistical). The
      integration must occur with the cancer care of the patient at all stages (from
      screening to palliative care) and across all clinical sites of care (inpatient
      and outpatient cancer services as well as primary care). In this article, we
      consider the challenges we face if we are to provide such integrated psychosocial
      services. We focus on the collaborative care service model. This model comprises
      systematic identification of need, integrated delivery of care by care managers,
      appropriate specialist supervision, and the stepping of care based on systematic
      measurement of outcomes. Several trials of this approach to the management of
      depression in patients with cancer have found it to be both feasible to deliver
      and effective. It provides a model for services to meet other psychosocial needs.
      We conclude by proposing the key components of an integrated psychosocial service
      that could be implemented now and by considering what we need to do next if we
      are to succeed in providing better and more comprehensive care to our patients.

PMID- 22412140
TI  - Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial
      comparing chemotherapy plus best supportive care with best supportive care alone.
AB  - PURPOSE: When designing this trial, there was no evidence that salvage
      chemotherapy (SLC) in advanced gastric cancer (AGC) resulted in substantial
      prolongation of survival when compared with best supportive care (BSC). However,
      SLC is often offered to pretreated patients with AGC for anecdotal reasons.
      PATIENTS AND METHODS: Patients with AGC with one or two prior chemotherapy
      regimens involving both fluoropyrimidines and platinum and with an Eastern
      Cooperative Oncology Group performance status (PS) 0 or 1 were randomly assigned
      in a ratio of 2:1 to SLC plus BSC or BSC alone. Choice of SLC-either docetaxel 60
      mg/m(2) every 3 weeks or irinotecan 150 mg/m(2) every 2 weeks-was left to the
      discretion of investigators. Primary end point was overall survival (OS).
      RESULTS: Median OS was 5.3 months among 133 patients in the SLC arm and 3.8
      months among 69 patients in the BSC arm (hazard ratio, 0.657; 95% CI, 0.485 to
      0.891; one-sided P = .007). OS benefit for SLC was consistent in most of the
      prospectively defined subgroups, including age, PS, number of prior treatments,
      metastatic sites, hemoglobin levels, and response to prior chemotherapy. SLC was
      generally well tolerated, and adverse events were similar in the SLC and BSC
      arms. We found no median OS difference between docetaxel and irinotecan (5.2 v
      6.5 months; P = .116). CONCLUSION: To our knowledge, this is the largest phase
      III trial comparing SLC plus BSC with BSC alone in AGC. In pretreated patients,
      SLC is tolerated and significantly improves OS when added to BSC.

PMID- 22412141
TI  - Serum mesothelin for diagnosing malignant pleural mesothelioma: an individual
      patient data meta-analysis.
AB  - PURPOSE: Mesothelin is currently considered the best available serum biomarker of
      malignant pleural mesothelioma. To examine the diagnostic accuracy and use of
      serum mesothelin in early diagnosis, we performed an individual patient data
      (IPD) meta-analysis. METHODS: The literature search identified 16 diagnostic
      studies of serum mesothelin, measured with the Mesomark enzyme-linked
      immunosorbent assay. IPD of 4,491 individuals were collected, including several
      control groups and 1,026 patients with malignant pleural mesothelioma. Mesothelin
      levels were standardized for between-study differences and age, after which the
      diagnostic accuracy and the factors affecting it were examined with receiver
      operating characteristic (ROC) regression analysis. RESULTS: At a common
      diagnostic threshold of 2.00 nmol/L, the sensitivities and specificities of
      mesothelin in the different studies ranged widely from 19% to 68% and 88% to
      100%, respectively. This heterogeneity can be explained by differences in study
      population, because type of control group, mesothelioma stage, and histologic
      subtype significantly affected the diagnostic accuracy. The use of mesothelin in
      early diagnosis was evaluated by differentiating 217 patients with stage I or II
      epithelioid and biphasic mesothelioma from 1,612 symptomatic or high-risk
      controls. The resulting area under the ROC curve was 0.77 (95% CI, 0.73 to 0.81).
      At 95% specificity, mesothelin displayed a sensitivity of 32% (95% CI, 26% to
      40%). CONCLUSION: In patients suspected of having mesothelioma, a positive blood
      test for mesothelin at a high-specificity threshold is a strong incentive to urge
      further diagnostic steps. However, the poor sensitivity of mesothelin clearly
      limits its added value to early diagnosis and emphasizes the need for further
      biomarker research.

PMID- 22412142
TI  - Dual targeting of the epidermal growth factor receptor using the combination of
      cetuximab and erlotinib: preclinical evaluation and results of the phase II DUX
      study in chemotherapy-refractory, advanced colorectal cancer.
AB  - PURPOSE: This preclinical and phase II study evaluated the efficacy and safety of
      the combination of cetuximab and erlotinib in metastatic colorectal cancer
      (mCRC). PATIENTS AND METHODS: The activity and mechanism of action of the
      combination of cetuximab plus erlotinib were investigated in vitro in colorectal
      cancer cell lines. In the clinical study, patients with chemotherapy-refractory
      mCRC were treated with cetuximab 400 mg/m(2) as a loading dose and then weekly
      cetuximab 250 mg/m(2) with erlotinib 100 mg orally daily. The primary end point
      was response rate (RR), which was evaluated separately in KRAS wild-type (WT)
      versus KRAS mutant tumors. Secondary end points included toxicity, progression
      free survival (PFS), and overall survival. Target accrual was 50 patients, with a
      one-stage design. RESULTS: Preclinical studies demonstrated synergistic activity
      of cetuximab and erlotinib cotreatment on growth inhibition of colon cancer cell
      lines both as a result of enhanced inhibition of the epidermal growth factor
      receptor pathway and differential effects on STAT3. In the clinical study, 50
      patients were enrolled, with 48 patients evaluable for response. The overall RR
      was 31% (95% CI, 26% to 57%), with a median PFS of 4.6 months (95% CI, 2.8 to 5.6
      months). RR was 41% (95% CI, 26% to 57%) in KRAS WT tumors, with a median PFS of
      5.6 months (95% CI, 2.9 to 5.6 months). There was no response in 11 patients with
      KRAS mutations. Frequent grade 3 and 4 toxicities were rash (48%),
      hypomagnesaemia (18%), and fatigue (10%). CONCLUSION: The combination of
      cetuximab and erlotinib synergistically inhibits growth of colon cancer cell
      lines, achieves promising efficacy in patients with KRAS WT mCRC, and merits
      evaluation in further randomized studies.

PMID- 22412144
TI  - Evidence-based treatment of depression in patients with cancer.
AB  - PURPOSE: Depression is a common condition in patients with cancer, although there
      has been a relative paucity of research on the effectiveness of treatment in this
      population. This review summarizes the psychosocial and pharmacologic treatment
      of depression in patients with cancer based on a consideration of evidence
      regarding etiologic factors and treatment outcomes. METHODS: A review of the
      evidence base for psychosocial and pharmacologic interventions for depression in
      patients with cancer was performed, including original studies, systematic
      reviews, and meta-analytic studies in the literature. RESULTS: Recent evidence
      from randomized controlled trials has demonstrated the efficacy of psychosocial
      and pharmacologic treatments to alleviate depression in patients with cancer.
      Further research is needed to establish their relative and combined efficacy and
      their role in the treatment of depression that is less severe and occurs in
      association with more advanced disease. First-line recommendations for the
      treatment of depression in patients with cancer are difficult to derive based on
      current evidence, because comparative studies have not been conducted to support
      the superiority of one treatment modality over another in this population.
      CONCLUSION: Both psychosocial and pharmacologic interventions have been shown to
      be efficacious in treating depression in cancer, but further research is needed
      to establish their relative and combined benefit. Future research directions
      include the development and evaluation of novel interventions targeted to
      specific biologic and psychosocial risk factors.

PMID- 22412143
TI  - Sorafenib in combination with capecitabine: an oral regimen for patients with
      HER2-negative locally advanced or metastatic breast cancer.
AB  - PURPOSE: Sorafenib is a multikinase inhibitor with
      antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo
      controlled phase IIB trial assessed sorafenib with capecitabine for locally
      advanced or metastatic human epidermal growth factor receptor 2 (HER2) -negative
      breast cancer. PATIENTS AND METHODS: Patients were randomly assigned to first- or
      second-line capecitabine 1,000 mg/m(2) orally twice a day for days 1 to 14 of
      every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The
      primary end point was progression-free survival (PFS). RESULTS: In total, 229
      patients were enrolled. The addition of sorafenib to capecitabine resulted in a
      significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard
      ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across
      subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line
      (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement
      for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23;
      P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v
      placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal
      inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and
      hand-foot skin reaction/hand- foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4
      toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%).
      Reasons for discontinuation in the sorafenib and placebo arms included disease
      progression (63% v 82%, respectively), adverse events (20% v 9%, respectively),
      and death (0% v 1%, respectively). CONCLUSION: Addition of sorafenib to
      capecitabine improved PFS in patients with HER2-negative advanced breast cancer.
      The dose of sorafenib used in this trial resulted in unacceptable toxicity for
      many patients. A phase III confirmatory trial has been initiated with a reduced
      sorafenib dose.

PMID- 22412145
TI  - Communication skills training for oncology professionals.
AB  - PURPOSE: To provide a state-of-the-art review of communication skills training
      (CST) that will guide the establishment of a universal curriculum for fellows of
      all cancer specialties undertaking training as oncology professionals today.
      METHODS: Extensive literature review including meta-analyses of trials,
      conceptual models, techniques, and potential curricula provides evidence for the
      development of an appropriate curriculum and CST approach. Examples from the
      Memorial Sloan-Kettering Cancer Center CST program are incorporated. RESULTS: A
      core curriculum embraces CST modules in breaking bad news and discussing
      unanticipated adverse events, discussing prognosis, reaching a shared treatment
      decision, responding to difficult emotions, coping with survivorship, running a
      family meeting, and transitioning to palliative care and end of life. Achievable
      outcomes are growth in clinician's self-efficacy, uptake of new communication
      strategies and skills, and transfer of these strategies and skills into the
      clinic. Outcomes impacting patient satisfaction, improved adaptation, and
      enhanced quality of life are still lacking. CONCLUSION: Future communication
      challenges include genetic risk communication, concepts like watchful waiting,
      cumulative radiation risk, late effects of treatment, discussing Internet
      information and unproven therapies, phase I trial enrollment, and working as a
      multidisciplinary team. Patient benefits, such as increased treatment adherence
      and enhanced adaptation, need to be demonstrated from CST.

PMID- 22412146
TI  - Screening for distress and unmet needs in patients with cancer: review and
      recommendations.
AB  - PURPOSE: This review summarizes the need for and process of screening for
      distress and assessing unmet needs of patients with cancer as well as the
      possible benefits of implementing screening. METHODS: Three areas of the relevant
      literature were reviewed and summarized using structured literature searches:
      psychometric properties of commonly used distress screening tools, psychometric
      properties of relevant unmet needs assessment tools, and implementation of
      distress screening programs that assessed patient-reported outcomes (PROs).
      RESULTS: Distress and unmet needs are common problems in cancer settings, and
      programs that routinely screen for and treat distress are feasible, particularly
      when staff are supported and links with specialist psychosocial services exist.
      Many distress screening and unmet need tools have been subject to preliminary
      validation, but few have been compared head to head in independent centers and in
      different stages of cancer. Research investigating the overall effectiveness of
      screening for distress in terms of improved recognition and treatment of distress
      and associated problems is not yet conclusive, but screening seems to improve
      communication between patients and clinicians and may enhance psychosocial
      referrals. Direct effects on quality of life are uncertain, but screening may
      help improve discussion of quality-of-life issues. CONCLUSION: Involving all
      stakeholders and frontline clinicians when planning screening for distress
      programs is recommended. Training frontline staff to deliver screening programs
      is crucial, and continuing to rigorously evaluate outcomes, including PROs,
      process of care, referrals, and economic costs and benefits is essential.

PMID- 22412147
TI  - Psychosocial care of adolescent and young adult patients with cancer and
      survivors.
AB  - The delivery of quality care for adolescent and young adult (AYA) patients with
      cancer and survivors requires an understanding of the unique qualities of this
      group--the shared norms, attitudes, and beliefs that determine their behavior as
      well as the unique stresses they face on a day-to-day basis. All AYAs have
      typical concerns about being comfortable with who they are and who they want to
      become (identity development, including sexual identity), their bodies (body
      image), initiating intimate and emotional relationships, separating from parents,
      and making independent decisions about future goals such as career, higher
      education, and/or family (autonomy). Yet efforts of AYA patients with cancer and
      survivors to mature are often confounded by restrictions and limitations placed
      on them by their disease and treatment. This article promotes understanding of
      psychosocial challenges faced by AYAs when diagnosed with and treated for cancer.
      It reviews evidence-based psychosocial support interventions for AYAs with cancer
      and other life-threatening or chronic diseases, particularly the positive effects
      of peer support, technology-based interventions, and skill-based interventions.
      The article concludes with recommendations for clinical care that are intended to
      promote the ability of AYAs to cope with cancer.

PMID- 22412149
TI  - Web-based tailored education program for disease-free cancer survivors with
      cancer-related fatigue: a randomized controlled trial.
AB  - PURPOSE: To determine whether an Internet-based tailored education program is
      effective for disease-free cancer survivors with cancer-related fatigue (CRF).
      PATIENTS AND METHODS: We randomly assigned patients who had completed primary
      cancer treatment within the past 24 months in any of four Korean hospitals and
      had reported moderate to severe fatigue for at least 1 week to participate in a
      12-week, Internet-based, individually tailored CRF education program or to
      receive routine care. We based the program on the CRF guidelines of the National
      Comprehensive Cancer Network (NCCN) and incorporated the transtheoretic model
      (TTM). At baseline and 12 weeks, we used the Brief Fatigue Inventory (BFI) and
      Fatigue Severity Scale (FSS) as primary outcomes and the Hospital Anxiety and
      Depression Scale (HADS) and European Organisation for Research and Treatment of
      Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) for secondary outcomes.
      RESULTS: We recruited 273 participants and randomly assigned 136 to the
      intervention group. Compared with the control group, the intervention group had
      an improvement in fatigue as shown by a significantly greater decrease in BFI
      global score (-0.66 points; 95% CI -1.04 to -0.27) and FSS total score (-0.49;
      95% CI, -0.78 to -0.21). In secondary outcomes, the intervention group
      experienced a significantly greater decrease in HADS anxiety score (-0.90; 95%
      CI, -1.51 to -0.29) as well as global quality of life (5.22; 95% CI, 0.93 to
      9.50) and several functioning scores of the EORTC QLQ-C30. CONCLUSION: An
      Internet-based education program based on NCCN guidelines and TTM may help
      patients manage CRF.

PMID- 22412148
TI  - Fatigue, inflammation, and omega-3 and omega-6 fatty acid intake among breast
      cancer survivors.
AB  - PURPOSE: Evidence suggests that inflammation may drive fatigue in cancer
      survivors. Research in healthy populations has shown reduced inflammation with
      higher dietary intake of omega-3 polyunsaturated fatty acids (PUFAs), which could
      potentially reduce fatigue. This study investigated fatigue, inflammation, and
      intake of omega-3 and omega-6 PUFAs among breast cancer survivors. METHODS: Six
      hundred thirty-three survivors (mean age, 56 years; stage I to IIIA)
      participating in the Health, Eating, Activity, and Lifestyle Study completed a
      food frequency/dietary supplement questionnaire and provided a blood sample
      assayed for C-reactive protein (CRP) and serum amyloid A (30 months after
      diagnosis) and completed the Piper Fatigue Scale and Short Form-36 (SF-36)
      vitality scale (39 months after diagnosis). Analysis of covariance and logistic
      regression models tested relationships between inflammation and fatigue,
      inflammation and omega-3 and omega-6 PUFA intake, and PUFA intake and fatigue,
      controlling for three incremental levels of confounders. Fatigue was analyzed
      continuously (Piper scales) and dichotomously (SF-36 vitality <= 50). RESULTS:
      Behavioral (P = .003) and sensory (P = .001) fatigue scale scores were higher by
      increasing CRP tertile; relationships were attenuated after adjustment for
      medication use and comorbidity. Survivors with high CRP had 1.8 times greater
      odds of fatigue after full adjustment (P < .05). Higher intake of omega-6
      relative to omega-3 PUFAs was associated with greater CRP (P = .01 after full
      adjustment) and greater odds of fatigue (odds ratio, 2.6 for the highest v lowest
      intake; P < .05). CONCLUSION: Results link higher intake of omega-3 PUFAs,
      decreased inflammation, and decreased physical aspects of fatigue. Future studies
      should test whether omega-3 supplementation may reduce fatigue among
      significantly fatigued breast cancer survivors.

PMID- 22412150
TI  - Financial hardship: a consequence of survivorship?

PMID- 22412151
TI  - Improved survival for children and adolescents with acute lymphoblastic leukemia
      between 1990 and 2005: a report from the children's oncology group.
AB  - PURPOSE: To examine population-based improvements in survival and the impact of
      clinical covariates on outcome among children and adolescents with acute
      lymphoblastic leukemia (ALL) enrolled onto Children's Oncology Group (COG)
      clinical trials between 1990 and 2005. PATIENTS AND METHODS: In total, 21,626
      persons age 0 to 22 years were enrolled onto COG ALL clinical trials from 1990 to
      2005, representing 55.8% of ALL cases estimated to occur among US persons younger
      than age 20 years during this period. This period was divided into three eras
      (1990-1994, 1995-1999, and 2000-2005) that included similar patient numbers to
      examine changes in 5- and 10-year survival over time and the relationship of
      those changes in survival to clinical covariates, with additional analyses of
      cause of death. RESULTS: Five-year survival rates increased from 83.7% in 1990
      1994 to 90.4% in 2000-2005 (P < .001). Survival improved significantly in all
      subgroups (except for infants age <= 1 year), including males and females; those
      age 1 to 9 years, 10+ years, or 15+ years; in whites, blacks, and other races; in
      Hispanics, non-Hispanics, and patients of unknown ethnicity; in those with B-cell
      or T-cell immunophenotype; and in those with National Cancer Institute (NCI)
      standard- or high-risk clinical features. Survival rates for infants changed
      little, but death following relapse/disease progression decreased and death
      related to toxicity increased. CONCLUSION: This study documents ongoing survival
      improvements for children and adolescents with ALL. Thirty-six percent of deaths
      occurred among children with NCI standard-risk features emphasizing that efforts
      to further improve survival must be directed at both high-risk subsets and at
      those children predicted to have an excellent chance for cure.

PMID- 22412152
TI  - Population-based 20-year survival among people diagnosed with thin melanomas in
      Queensland, Australia.
AB  - PURPOSE: The 20-year survival rates are unknown for the majority of melanoma
      patients-those with thin melanomas. We determined 20-year survival rates of
      patients diagnosed with thin melanomas (<= 1.00 mm) in the general population and
      also determined the main prognostic factors. PATIENTS AND METHODS: Available
      clinical and histologic data from the Queensland Cancer Registry were obtained
      for all patients diagnosed with a single thin invasive melanoma from 1982 to 2006
      and matched against national death registration data. Melanoma-specific survival
      estimates to December 31, 2007, were assessed, and subgroup differences in
      prognosis were determined by fitting multivariate Cox proportional hazard models.
      RESULTS: Among 26,736 people in the state of Queensland diagnosed with thin
      melanomas, the 20-year survival was 96%. The most influential determinants of
      prognosis were tumor thickness >= 0.75 mm (adjusted hazard ratio [HR], 4.33; 95%
      CI, 2.8 to 6.8 compared with tumors < 0.25 mm) and patient age at diagnosis older
      than 65 years (HR, 2.8; 95% CI, 1.8 to 4.5) compared with age younger than 25
      years. Acral lentiginous and nodular tumors, male sex, tumor site on the scalp or
      neck, or tumor invasion of the entire papillary dermis each independently
      increased the risk of dying from thin invasive melanoma. CONCLUSION: The outlook
      for patients with thin invasive melanoma is positive, although continued clinical
      vigilance is warranted for patients with nodular melanoma and those with the
      thickest tumors.

PMID- 22412153
TI  - 'The Anglo-Saxon disease': a pilot study of the barriers to and facilitators of
      the use of randomised controlled trials of social programmes in an international
      context.
AB  - BACKGROUND: There appears to be considerable variation between different national
      jurisdictions and between different sectors of public policy in the use of
      evidence and particularly the use of randomised controlled trials (RCTs) to
      evaluate non-healthcare sector programmes. METHODS: As part of a wider study
      attempting to identify RCTs of public policy sector programmes and the reasons
      for variation between countries and sectors in their use, we carried out a pilot
      study which interviewed 10 policy makers and researchers in six countries to
      elicit views on barriers to and facilitators of the use of RCTs for social
      programmes. RESULTS: While in common with earlier studies, those interviewed
      expressed a need for unambiguous findings, timely results and significant effect
      sizes, users could, in fact, be ambivalent about robust methods and robust
      answers about what works, does not work or makes no difference, particularly
      where investment or a policy announcement was planned. Different national and
      policy sector cultures varied in their use of and support for RCTs. CONCLUSIONS:
      In order to maximise the use of robust evaluations of public programmes across
      the world it would be useful to examine, systematically, cross-national and cross
      sectoral variations in the use of different methods including RCTs and barriers
      to and facilitators of their use. Sound research methods, whatever their
      scientific value, are no guarantee that findings will be useful or used.
      'Stories' have been shown to influence policy; those advocating the use of RCTs
      may need to provide convincing narratives to avoid repetition about their value.

PMID- 22412154
TI  - Does income matter for troublesome neck pain? A population-based study on risk
      and prognosis.
AB  - BACKGROUND: Studies have shown associations between higher income and better
      health, but income has not been studied in relation to neck pain. The aims of
      this cohort study were to assess the sex-specific role of disposable income for
      onset and prognosis of neck pain in the general population and if economic stress
      influences such potential associations. METHODS: Two subcohorts were identified
      in the Stockholm Public Health Cohort with data from 2002. Cohort I (risk cohort)
      included persons without neck pain (n=8348). Cohort II (prognostic cohort)
      included persons with occasional neck pain during the previous 6 months (n=10
      523). Both cohorts were assessed for long duration troublesome neck pain (LDNP)
      in 2007. Individual income was defined as aggregated annual family income in 2002
      with each family member assigned a weighted consumption share, based on salary,
      pensions and social benefits. LDNP in 2007 was defined as having had troublesome
      neck pain lasting for three or more consecutive months the previous 5 years.
      Association between income and LDNP, considering potential confounding, was
      investigated by multivariable logistic regression. Economic stress was tested as
      effect modifier between income and LDNP. RESULTS: In both cohorts, associations
      were found between lower income and a higher risk for LDNP. The results were
      similar between the sexes. Economic stress modified the associations in both
      cohorts. CONCLUSIONS: Low income may be a risk as well as prognostic factor for
      developing LDNP. Furthermore, the results indicate that economic stress may be an
      underlying factor to consider when studying associations between income and neck
      pain.

PMID- 22412155
TI  - Association of risky alcohol consumption and accreditation in the 'Good Sports'
      alcohol management programme.
AB  - BACKGROUND: Involvement in community sports clubs is often associated with high
      levels of risky alcohol consumption; however, developing prevention-focused
      interventions in these settings can be complex. We examined the association of
      reduced risky alcohol consumption with the implementation of the Good Sports
      Programme (GSP)--a programme that accredits clubs in three stages, on the basis
      of their implementation of alcohol-related harm reduction strategies. METHODS:
      Using a cross section of football and cricket clubs, consumption was compared
      between clubs accredited at level 1, 2 or 3 of the GSP and clubs not accredited
      (92 clubs; 1924 individuals). Drinking above Australian guidelines for short-term
      risk (more than four standard drinks) on the last playing day prior to the survey
      and drinking at the club over the last 12 months at average levels exceeding
      short- and long-term risk (more than two standard drinks) guidelines were also
      examined. RESULTS: Multilevel modelling indicated that higher accreditation stage
      (0, 1, 2, 3) was associated with a 0.79 reduction in the odds of risky
      consumption on the playing day; a 0.85 reduction in the odds for short-term risky
      drinking, and a 0.86 reduction in long-term risky drinking. CONCLUSIONS: The
      findings suggest that higher accreditation in the GSP is associated with reduced
      rates of risky alcohol use at a population level.

PMID- 22412156
TI  - Histone H3 lysine 9 di-methylation as an epigenetic signature of the interferon
      response.
AB  - Effective antiviral immunity depends on the ability of infected cells or cells
      triggered with virus-derived nucleic acids to produce type I interferon (IFN),
      which activates transcription of numerous antiviral genes. However,
      disproportionately strong or chronic IFN expression is a common cause of
      inflammatory and autoimmune diseases. We describe an epigenetic mechanism that
      determines cell type-specific differences in IFN and IFN-stimulated gene (ISG)
      expression in response to exogenous signals. We identify di-methylation of
      histone H3 at lysine 9 (H3K9me2) as a suppressor of IFN and IFN-inducible
      antiviral gene expression. We show that levels of H3K9me2 at IFN and ISG
      correlate inversely with the scope and amplitude of IFN and ISG expression in
      fibroblasts and dendritic cells. Accordingly, genetic ablation or pharmacological
      inactivation of lysine methyltransferase G9a, which is essential for the
      generation of H3K9me2, resulted in phenotypic conversion of fibroblasts into
      highly potent IFN-producing cells and rendered these cells resistant to
      pathogenic RNA viruses. In summary, our studies implicate H3K9me2 and enzymes
      controlling its abundance as key regulators of innate antiviral immunity.

PMID- 22412157
TI  - Structural insight into MR1-mediated recognition of the mucosal associated
      invariant T cell receptor.
AB  - Mucosal-associated invariant T (MAIT) cells express a semiinvariant alphabeta T
      cell receptor (TCR) that binds MHC class I-like molecule (MR1). However, the
      molecular basis for MAIT TCR recognition by MR1 is unknown. In this study, we
      present the crystal structure of a human Valpha7.2Jalpha33-Vbeta2 MAIT TCR.
      Mutagenesis revealed highly conserved requirements for the MAIT TCR-MR1
      interaction across different human MAIT TCRs stimulated by distinct microbial
      sources. Individual residues within the MAIT TCR beta chain were dispensable for
      the interaction with MR1, whereas the invariant MAIT TCR alpha chain controlled
      specificity through a small number of residues, which are conserved across
      species and located within the Valpha-Jalpha regions. Mutagenesis of MR1 showed
      that only two residues, which were centrally positioned and on opposing sides of
      the antigen-binding cleft of MR1, were essential for MAIT cell activation. The
      mutagenesis data are consistent with a centrally located MAIT TCR-MR1 docking
      that was dominated by the alpha chain of the MAIT TCR. This candidate docking
      mode contrasts with that of the NKT TCR-CD1d-antigen interaction, in which both
      the alpha and beta chain of the NKT TCR is required for ligation above the F'
      pocket of CD1d.

PMID- 22412159
TI  - Effect of pimobendan on the clinical outcome and survival of cats with non
      taurine responsive dilated cardiomyopathy.
AB  - This retrospective study was designed to assess the effect of pimobendan on the
      median survival time (MST) of cats with non-taurine responsive dilated
      cardiomyopathy (DCM). Thirty-two client-owned cats with a left ventricular
      internal dimension at end systole (LVIDs) >14 mm, a fractional shortening (FS)
      <28% and a lack of response to taurine therapy were included over a 9-year period
      (2001-2010). These cats were divided into pimobendan (n=16) and non-pimobendan
      (n=16) treatment groups. All cats received standard treatment with frusemide,
      taurine and benazepril or enalapril. Nine cats in the non-pimobendan group also
      received digoxin. The MST of the pimobendan group (49 days; range 1 to >502 days)
      was four times that of the non-pimobendan group (12 days; 1 to 244 days). The
      difference in survival between the two groups was statistically significant (P =
      0.048). Hypothermia and FS <20% were associated with a poor prognosis. No adverse
      effects to pimobendan were noted.

PMID- 22412158
TI  - The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic
      egress of mature thymocytes.
AB  - The Mst1 kinase is an important regulator of murine T cell adhesion, migration,
      proliferation, and apoptosis. In this study, we analyze mice lacking both Mst1
      and Mst2 in hematopoietic cells. Compared with wild-type mice, these double
      knockout (DKO) mice exhibit a severe reduction in the number of mature T cells in
      the circulation and in secondary lymphoid organs (SLOs). CD4(+)CD8(-) and CD4(
      )CD8(+) single-positive (SP) thymocytes in DKO mice resemble mature T cells of
      wild-type mice but undergo excessive apoptosis, and their egress from the thymus
      is reduced by >90%. Even when placed directly in the circulation, DKO SP
      thymocytes failed to enter SLOs. In SP thymocytes, deficiency of Mst1 and Mst2
      abolished sphingosine-1 phosphate- and CCL21-induced Mob1 phosphorylation, Rac1
      and RhoA GTP charging, and subsequent cell migration. When phosphorylated by Mst1
      or Mst2, Mob1 binds and activates the Rac1 guanyl nucleotide exchanger Dock8,
      which is abundant in the thymus. Thus, the Mst1 and Mst2 kinases control Rho
      GTPase activation and the migratory responses of SP thymocytes.

PMID- 22412160
TI  - Open-label trial of a multi-strain synbiotic in cats with chronic diarrhea.
AB  - This study was designed to test the hypothesis that in cats with chronic diarrhea
      the daily administration of a proprietary synbiotic (Proviable-DC) would result
      in an improvement in stool character, as assessed by the owner. Adult cats with
      chronic diarrhea were recruited for the study and screened for systemic diseases.
      Fecal flotation, wet mount, immunofluorescence assay (IFA) for Giardia and
      Cryptosporidium species, and Tritrichomonas species polymerase chain reactions
      (PCRs) were used to screen for intestinal parasitism. The synbiotic was
      administered for 21 days; otherwise, no changes were made to ongoing treatment(s)
      or diet. The severity of the diarrhea was assessed using a standardized fecal
      scoring system and the owner's subjective perception before, and after,
      supplementation. The mean fecal score for the 53 cats completing the study
      decreased from 6.0 to 4.4, representing a significantly (P <0.001) firmer stool
      character. Seventy-two percent of owners perceived an improvement in their cat's
      diarrhea following a 21-day course of synbiotic supplementation.

PMID- 22412161
TI  - Hypertrophic cardiomyopathy in the Sphynx cat: a retrospective evaluation of
      clinical presentation and heritable etiology.
AB  - Hypertrophic cardiomyopathy is an inherited disease in some feline breeds
      including the Maine Coon and Ragdoll. In these breeds, distinct causative genetic
      mutations have been identified. The two breeds appear to have slightly different
      clinical presentations, including age of diagnosis. The observation that these
      two breeds may have different clinical presentations, as well as different
      genetic mutations, suggests that hypertrophic cardiomyopathy is a diverse disease
      in the cat. Hypertrophic cardiomyopathy is poorly described in the Sphynx. The
      objective of this study was to phenotypically characterize Sphynx hypertrophic
      cardiomyopathy and to evaluate for a familial etiology. Records of 18 affected
      cats (11 female, seven male) were evaluated. Age of affected cats ranged from 0.5
      to 7 years (median, 2 years). Four affected cats were from a single family and
      included an affected cat in each of four generations (three females, one male).
      Further studies are warranted to evaluate for a causative mutation and better
      classify the phenotypic expression.

PMID- 22412162
TI  - Slowly progressive lymphohistiocytic meningoencephalomyelitis in 21 adult cats
      presenting with peculiar neurological signs.
AB  - Twenty-one cats presented with a history of slowly progressive neurological signs
      characterised by a stiff extended tail, behavioural changes, and spastic and
      ataxic gait. All cats had outdoor access and lived in the same geographical rural
      area in north-east Scotland. Histological findings were consistent with
      lymphohistiocytic meningoencephalomyelitis. Immunohistochemistry ruled out 15
      pathogens and showed a significant expression of the interferon-inducible Mx
      protein, suggesting an as yet unidentified infective or environmental immunogenic
      trigger as the possible causative agent. The late age at onset (mean 9 years),
      the very slow progression of clinical signs (mean 11 months) and the peculiar
      clinical presentation (particularly the posture of the tail) have not been
      reported previously in cats with lymphohistiocytic meningoencephalomyelitis.

PMID- 22412163
TI  - Interaction of clarithromycin with cyclosporine in cats: pharmacokinetic study
      and case report.
AB  - Clarithromycin (CLM) has been known to increase the cyclosporine (CsA) trough
      levels in human transplant patients. However, the interaction of CLM with CsA has
      not been reported in cats. In this study, the effects of oral dosing of CLM on
      the pharmacokinetics and dosing of CsA in cats were investigated. Co
      administration of CLM with CsA resulted in significant increases of oral
      bioavailability of CsA. In addition, CLM reduced the CsA dosage required to
      maintain the therapeutic CsA trough levels to almost 35% of the initial CsA
      therapy and the dose frequency was successfully replaced from a twice a day
      schedule to once a day in a feline kidney transplant patient. The addition of CLM
      to the regular CsA-based immunosuppression could be used as an effective
      alternative to classical ketoconazole treatment in feline kidney transplant
      patients and may result in substantial cost saving and convenience for the cat
      owners.

PMID- 22412164
TI  - Gastrointestinal small-cell lymphoma with gall bladder involvement in a cat.
AB  - A 13-year-old female spayed domestic shorthair cat presented for investigation of
      decreased appetite and increased serum liver enzyme concentrations. An abdominal
      ultrasound revealed multiple sessile hyperechoic structures along the luminal
      aspect of the gall bladder wall and a mildly enlarged liver with hyperechoic
      nodules. Cholecystectomy was performed and biopsies were obtained by laparotomy.
      Histopathologic examination with immunohistochemistry was consistent with a
      diagnosis of small-cell lymphoma of T cells within the gall bladder, liver and
      small intestine. Clonality testing confirmed the diagnosis. The cat remains
      clinically stable 23 months after institution of treatment with prednisolone,
      chlorambucil and ursodeoxycholic acid. This is the first report of small-cell
      lymphoma in the gall bladder of a cat.

PMID- 22412165
TI  - Unilateral forelimb partial aphalangia in a kitten.
AB  - Congenital limb deformities are rarely reported in the cat. The macroscopic and
      radiographic features of aphalangia are described in a 2-month-old male kitten
      showing a shortened limb that ended, at the level of the carpus, in a stump
      without digits. A nail was present at the level of the first phalanx and on the
      palmar surface only two footpads were present. The radiographs showed an absence
      of phalanges. The first metacarpal and the proximal and distal phalanges of digit
      1 were present. The deformed metacarpal bones were reduced in length; the carpal
      bones were incompletely ossified. This defect is a rare condition in many animal
      species. To the author's knowledge, the congenital fore limb deformity described
      here is the first documented case in a cat.

PMID- 22412166
TI  - Doppler echocardiographic diagnosis and surgical therapy of constrictive
      pericarditis in a cat.
AB  - A 4-year-old Ragdoll cat presented for dyspnea secondary to chylous pleural
      effusion to the University of Georgia Veterinary Teaching Hospital. Physical
      examination, complete blood count, serum chemistries, urinalysis, thoracic
      radiographs, abdominal radiographs, and thoracic fluid cytology and culture
      failed to identify an etiology for the chylous effusion. The patient tested
      negative for feline leukemia virus, feline immunodeficiency virus and heartworm
      disease. Respiration phasic influences on early diastolic trans-mitral, trans
      tricuspid and pulmonary vein blood flow velocities during Doppler
      echocardiography were consistent with constrictive pericarditis. The cat
      underwent subtotal pericardectomy. The patient recovered without complication and
      is overtly healthy without radiographic or echocardiographic abnormalities 6
      months post-surgery. Constrictive pericarditis should be considered in cats with
      idiopathic pleural effusion, with or without ascites, in which standard
      echocardiographic assessment is not suggestive of structural heart disease. If
      constrictive pericarditis is present, the Doppler characteristics outlined here
      may allow for this diagnosis to be made. Pericardectomy may be highly rewarding,
      although the specific etiology of the constrictive pericarditis may remain
      unknown.

PMID- 22412167
TI  - Radiological investigation of an over 2000-year-old Egyptian mummy of a cat.
AB  - A radiographical study of a cat mummy from the Egyptian collection of the
      National Archeological Museum in Parma, Italy was carried out in order to
      evaluate the content and to describe how cats were wrapped and mummified. The
      mummy contained the complete skeleton of a 4-5-month-old cat. Radiology revealed
      the position of the cat's body; it was wrapped to occupy the smallest space
      possible. In order to better position the cat, the ribs of the thorax were
      compressed cranio-caudally and the fore limbs were then positioned very close to
      the thorax. The hind limbs were flexed close to the lumbar spine and the tibio
      tarsal joints were subluxated to allow the repositioning of the tarsal,
      metatarsal and phalanx bones cranio-caudally near the tibiae. A coccygeal
      vertebra was fractured in order to reposition the tail as close as possible to
      the body. Atlanto-occipital subluxation and a fracture/hole was present in the
      occipital region of the skull: whether this was made for draining skull contents
      as a mummification process and/or to euthanase the cat remains open for
      discussion.

PMID- 22412168
TI  - Omentalisation of the head in cats: a cadaver study.
AB  - The involvement of the greater omentum in reconstructive, abdominal and thoracic
      surgery is based on its manifold qualities, which include immunological support,
      lymphatic drainage, angiogenesis, adhesion, haemostasis and fat storage. The
      purpose of this study was to determine whether the greater omentum could be
      extended to the head. In addition, we evaluated the surgical procedures necessary
      for this extension. Our study reveals that specific surgical lengthening
      techniques of the greater omentum, such as dorsal extension and inverted L-shape
      elongation, are necessary to successfully transpose the omentum to the head in
      cats. As the survival of the omentum after transposition procedures is still
      unknown, its application in chronic non-healing wounds of the head in cats
      warrants further investigation.

PMID- 22412169
TI  - Chinese lacto-vegetarian diet exerts favorable effects on metabolic parameters,
      intima-media thickness, and cardiovascular risks in healthy men.
AB  - BACKGROUND: To investigate whether the Chinese lacto-vegetarian diet has
      protective effects on metabolic and cardiovascular disease (CVD). METHODS: One
      hundred sixty-nine healthy Chinese lacto-vegetarians and 126 healthy omnivore men
      aged 21-76 years were enrolled. Anthropometric indexes, lipid profile, insulin
      sensitivity, pancreatic beta cell function, and intima-media thickness (IMT) of
      carotid arteries were assessed and compared. Cardiovascular risk points and
      probability of developing CVD in 5-10 years in participants aged 24-55 years were
      calculated. RESULTS: Compared with omnivores, lacto-vegetarians had remarkably
      lower body mass index, systolic and diastolic blood pressure, and serum levels of
      triglyceride, total cholesterol, low-density lipoprotein cholesterol,
      apolipoprotein B, gamma-glutamyl transferase, serum creatinine, uric acid,
      fasting blood glucose, as well as lower total cholesterol/high-density
      lipoprotein cholesterol ratio. Vegetarians also had higher homeostasis model
      assessment beta cell function and insulin secretion index and thinner carotid IMT
      than the omnivores did. These results corresponded with lower cardiovascular risk
      points and probability of developing CVD in 5-10 years in vegetarians 24-55 years
      old. CONCLUSIONS: In healthy Chinese men, the lacto-vegetarian diet seems to
      exert protective effects on blood pressure, lipid profiles, and metabolic
      parameters and results in significantly lower carotid IMT. Lower CVD risks found
      in vegetarians also reflect the beneficial effect of the Chinese lacto-vegetarian
      diet.

PMID- 22412170
TI  - Low-frequency repetitive TMS plus anodal transcranial DCS prevents transient
      decline in bimanual movement induced by contralesional inhibitory rTMS after
      stroke.
AB  - BACKGROUND: Low-frequency repetitive transcranial magnetic stimulation (rTMS)
      over the unaffected motor cortex may improve motor function of the paretic hand
      after stroke. However, low-frequency rTMS might adversely affect bimanual
      movement by decreasing transcallosal function. OBJECTIVE: The authors
      investigated whether combined administration of rTMS and transcranial direct
      current stimulation (tDCS) prevents deterioration of bimanual movement induced by
      low-frequency rTMS over the unaffected hemisphere. METHODS: A total of 27
      participants with chronic subcortical stroke were randomly assigned to receive
      either 1 Hz rTMS over the unaffected hemisphere, anodal tDCS over the affected
      hemisphere, or a combination of rTMS and tDCS. All patients performed a pinching
      motor-training task after stimulation. Bimanual movement and transcallosal
      inhibition (TCI) were evaluated after stimulation. RESULTS: rTMS and rTMS-tDCS
      enhanced the motor training effect on the paretic hand. rTMS decreased bimanual
      coordination and reduced TCI from the unaffected to the affected hemisphere
      (TCI(unaff-aff)). rTMS-tDCS changed TCI balance of both hemispheres but did not
      affect bimanual coordination or TCI(unaff-aff). The change in bimanual
      coordination was negatively correlated with TCI(unaff-aff). Following
      stimulation, improvement in the pinch force in the paretic hand was negatively
      correlated with TCI balance. CONCLUSIONS: Inhibitory rTMS over the unaffected
      hemisphere transiently caused deterioration of bimanual movements for the current
      task in stroke patients. This short-term decline was prevented by combined
      administration of low-frequency rTMS over the unaffected hemisphere and anodal
      tDCS over the affected hemisphere. These responses to bihemispheric stimulation
      suggest possible caution and opportunities for the rehabilitation of hand
      function after stroke.

PMID- 22412171
TI  - Theta burst stimulation in the rehabilitation of the upper limb: a
      semirandomized, placebo-controlled trial in chronic stroke patients.
AB  - BACKGROUND: Noninvasive cortical stimulation could represent an add-on treatment
      to enhance motor recovery after stroke. However, its clinical value, including
      anticipated size and duration of the treatment effects, remains largely unknown.
      OBJECTIVE: The authors designed a small semi-randomized clinical trial to explore
      whether long-lasting clinically important gains can be achieved by adding theta
      burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation
      (TMS), to a rehabilitation program for the hand. METHODS: A total of 41 chronic
      stroke patients received excitatory TBS to the ipsilesional hemisphere or
      inhibitory TBS to the contralesional hemisphere in 2 centers; each active group
      was compared with a group receiving sham TBS. TBS was followed by physical
      therapy for 10 working days. Patients and therapists were blinded to the type of
      TBS. Primary outcome measures (9-hole Peg Test [9HPT], Jebsen Taylor Test [JTT],
      and grip and pinch-grip dynamometry) were assessed 4, 30, and 90 days post
      treatment. The clinically important difference was defined as 10% of the maximum
      score. RESULTS: There were no differences between the active treatment and sham
      groups in any of the outcome measures. All patients achieved small sustainable
      improvements--9HPT, 5% of maximum (confidence interval [CI] = 3%-7%); JTT, 5.7%
      (CI = 3%-8%); and grip strength, 6% (CI = 2%-10%)--all below the defined
      clinically important level. CONCLUSIONS: Cortical stimulation did not augment the
      gains from a late rehabilitation program. The effect size anticipated by the
      authors was overestimated. These results can improve the design of future work on
      therapeutic uses of TMS.

PMID- 22412173
TI  - Effects of fast functional exercise on muscle activity after stroke.
AB  - BACKGROUND: In stroke rehabilitation, considerable emphasis is placed on
      improving muscle strength with less focus on the speed of movement. Muscle power
      (product of force and velocity) is essential for balance and mobility but
      velocity of movement is impaired after stroke. OBJECTIVE: The purpose of this
      efficacy study is to determine if a single session of fast functional movements
      can increase muscle activation and the speed of movement in participants with a
      subacute stroke. METHODS: In total, 32 individuals poststroke and 32 age- and sex
      matched controls performed a single session of 50 fast squats and steps.
      Electromyographic (EMG) activity was measured bilaterally in the rectus femoris
      (RF), biceps femoris (BF), tibialis anterior (TA), and soleus muscles. The
      average EMG area and the movement speed were calculated over 10 trials. The
      effect of exercise was determined as the change from the second set (Start) to
      the last set (End) of 10 trials. RESULTS: The stroke group had significant
      increases in EMG area of the TA, BF, and RF during the squatting exercise. There
      was an increase in EMG area of the RF and BF when the paretic leg was stepping.
      Improvements in EMG area of the soleus and RF when the paretic leg was in stance
      accompanied increases in EMG area when the nonparetic leg was stepping. There was
      a trend for improved movement speed for both exercises. CONCLUSION: A single
      session of exercises emphasizing speed of movement can be used to improve muscle
      activation in persons with mild to moderately severe strokes.

PMID- 22412172
TI  - Should body weight-supported treadmill training and robotic-assistive steppers
      for locomotor training trot back to the starting gate?
AB  - Body weight-supported treadmill training (BWSTT) and robotic-assisted step
      training (RAST) have not, so far, led to better outcomes than a comparable dose
      of progressive over-ground training (OGT) for disabled persons with stroke,
      spinal cord injury, multiple sclerosis, Parkinson's disease, or cerebral palsy.
      The conceptual bases for these promising rehabilitation interventions had once
      seemed quite plausible, but the results of well-designed, randomized clinical
      trials have been disappointing. The authors reassess the underpinning concepts
      for BWSTT and RAST, which were derived from mammalian studies of treadmill
      induced hind-limb stepping associated with central pattern generation after low
      thoracic spinal cord transection, as well as human studies of the triple crown
      icons of task-oriented locomotor training, massed practice, and activity-induced
      neuroplasticity. The authors retrospectively consider where theory and practice
      may have fallen short in the pilot studies that aimed to produce thoroughbred
      interventions. Based on these shortcomings, the authors move forward with
      recommendations for the future development of workhorse interventions for
      walking. In the absence of evidence for physical therapists to employ these
      strategies, however, BWSTT and RAST should not be provided routinely to disabled,
      vulnerable persons in place of OGT outside of a scientifically conducted efficacy
      trial.

PMID- 22412174
TI  - Non-canonical alternatives: what a macrophage is 4.
AB  - Macrophages play pleiotropic, niche-specific roles in all tissues and organs. As
      immune sentinels, tissue macrophages regulate immune activation and inflammation;
      in turn, their function is modulated by inflammatory mediators deriving from such
      activation. Recent papers have established unanticipated roles for interleukin 4
      and the alternative activation of tissue macrophages in the organismal response
      to diverse environmental stressors.

PMID- 22412175
TI  - Gene profiling of CD11b+ and CD11b- B1 cell subsets reveals potential cell
      sorting artifacts.

PMID- 22412176
TI  - Human CD11b+ B1 cells are not monocytes: A reply to "Gene profiling of CD11b+ and
      CD11b- B1 cell subsets reveals potential cell sorting artifacts".

PMID- 22412177
TI  - Tracheotomy timing and outcomes in the critically ill.
AB  - OBJECTIVE: To examine the impact of early tracheotomy in nontrauma patients on
      duration of mechanical ventilation (MV), intensive care unit (ICU) stay, and
      overall hospital stay. DESIGN: Case series with chart review. SETTING: Tertiary
      care medical center. METHODS: A retrospective study was performed for patients
      undergoing tracheotomy from 2005 to 2010. Demographics; survival; duration of
      endotracheal intubation, MV, ICU, and overall hospital stay; and incidence of
      ventilator-associated pneumonia (VAP) were assessed. Tracheotomy was considered
      early if it was performed by day 7 of MV and late thereafter. Nonparametric
      statistics were used to compare results from each group. RESULTS: Of the 592
      patients included in the analysis, 128 received tracheotomy early and 464 late.
      Differences between age, sex, and overall survival were not statistically
      significant. Duration of MV was 45% less (mean +/- standard error: 21.47 +/- 1.86
      days vs 39.33 +/- 1.33 days; P < .001), total ICU stay was shortened by 33%
      (17.52 +/- 1.38 days vs 26.27 +/- 0.73 days; P < .001), and length of overall
      hospital course was reduced by 34% (35.85 +/- 2.57 days vs 54.28 +/- 1.60 days; P
      < .001) in the early tracheotomy group. Three patients (2.3%) from the early
      tracheotomy group developed VAP as compared with 15 (3.2%) from the late group.
      Duration from tracheotomy to ICU transfer and 30% overall mortality did not
      differ significantly between groups. CONCLUSION: Early tracheotomy in ICU
      patients is associated with earlier ICU discharge, shorter duration of mechanical
      ventilation, and decreased length of overall hospital stay without affecting
      mortality.

PMID- 22412178
TI  - Modified adenotonsillectomy to improve cure rates for pediatric obstructive sleep
      apnea: a randomized controlled trial.
AB  - OBJECTIVE: To compare the efficacy of adenotonsillectomy (T&A) with and without
      pharyngoplasty (tonsillar pillar closure) in the treatment of pediatric
      obstructive sleep apnea-hypopnea syndrome (OSAHS). STUDY DESIGN: Randomized
      single-blind controlled study. SETTING: Tertiary care center. SUBJECTS AND
      METHODS: Sixty pediatric patients with a clinical diagnosis of OSAHS presenting
      between January 2009 and December 2010 were enrolled and randomized to undergo
      either standard T&A (n = 30) or T&A with pharyngoplasty (n = 30). Surgical cure
      was defined as apnea-hypopnea index (AHI) <5 plus OSA-18 health-related quality
      of-life (HRQL) score <60. Other outcomes included postsurgical AHI and minimum
      oxygen saturation (SpO(2)) improvement, changes in OSA-18 scores at 1 month, and
      postsurgical days to resume normal diet and activity. RESULTS: Three patients
      from each group did not undergo surgery. Of the 54 patients treated, 8 from the
      pharyngoplasty group and 2 from the standard group were lost to follow-up.
      Intention-to-treat analysis revealed no difference in cure rate between groups
      (standard 60%, pharyngoplasty 56.6%, P = .793). Limiting analysis to those
      patients with complete data, a higher, but not significantly increased, cure rate
      with pharyngoplasty was noted (72% vs 89.5%, P = .155). Greater OSA-18
      improvement (P = .036) and greater (although nonsignificant) AHI improvement and
      earlier return to normal function were noted with pharyngoplasty. CONCLUSION: The
      addition of pharyngoplasty to traditional adenotonsillectomy did not
      significantly improve OSAHS cure rates as measured by sleep testing and HRQL,
      although a nonsignificant increase in cure rate was observed in those who
      completed the study protocol. An unexpectedly high rate of patient dropout
      rendered the study statistically underpowered and therefore inconclusive.

PMID- 22412180
TI  - Retraction. Computed tomography in 15 congenital aural atresia patients and
      floating mass transducer on the round window.

PMID- 22412179
TI  - Disparate molecular, histopathology, and clinical factors in head and neck
      squamous cell carcinoma racial groups.
AB  - OBJECTIVE: There is a lack of consensus regarding the causes of the differences
      in the higher incidence of and the mortality from head and neck squamous cell
      carcinoma (HNSCC) in African Americans (AA) versus Caucasian Americans (CA). We
      examined a comprehensive array of risk factors influencing health and disease in
      an access-to-care, racially diverse, primary HNSCC cohort. STUDY DESIGN: Cross
      sectional study. SETTING: Primary care academic health care system. SUBJECTS AND
      METHODS: The cohort of 673 patients comprised 391 CA and 282 AA (42%). Risk
      variables included demographic, histopathology, and clinical/epidemiologic
      factors. Tumor DNA was interrogated for loss and gain of 113 genes with known
      involvement in HNSCC/cancer. Logistic regression for univariate analysis was
      followed by multivariate modeling with determination of model predictability (c
      index). RESULTS: Of the 39 univariate differences between AA and CA, multivariate
      modeling (c-index = 0.81) retained 7 differences (P < .05). AA were less likely
      to be married and more likely to have tumor lymphocytic response, undergo
      radiation treatment, and smoke. Insurance type was a significant predictor of
      race. AA were more likely to have Medicaid, Medicare, and other HMO types. AA
      tumors were more likely to have loss of CDKN2A and gain of SCYA3 versus CA.
      CONCLUSIONS: Multivariate modeling indicated significant differences between AA
      and CA HNSCC for histopathology, treatment, smoking, marital status, type of
      insurance, and tumor gene copy number alterations. Our data reiterate that for
      HNSCC, as in the case of other complex diseases, tumor genetics or biology is
      only one of many potential contributors to differences among racial groups.

PMID- 22412181
TI  - Screening of SLC26A4, FOXI1, KCNJ10, and GJB2 in bilateral deafness patients with
      inner ear malformation.
AB  - OBJECTIVE: Bilateral nonsyndromic sensorineural hearing loss associated with
      inner ear malformation is closely related to genetics. SLC26A4 is considered to
      be the major involved gene. Recently, FOXI1 and KCNJ10 mutations have been linked
      to enlarged vestibular aqueducts and GJB2 mutations linked to temporal bone
      malformation. The authors aimed to investigate the mutation spectrums of these
      genes in Chinese patients with bilateral hearing impairment associated with inner
      ear malformation. STUDY DESIGN: Cross-sectional study. SETTING: Affiliated
      hospital of the university. SUBJECTS AND METHODS: The authors analyzed the GJB2,
      SLC26A4, FOXI1, and KCNJ10 gene sequences in 43 patients presenting with
      bilateral hearing impairment associated with inner ear malformation using
      pyrosequencing and direct DNA sequencing. RESULTS: In total, 74.4% (32/43) of
      patients carried at least 1 of 14 pathogenic SLC26A4 mutations, including 6 novel
      mutations and 4 polymorphisms. Patients with enlarged vestibular aqueducts had a
      higher rate of SLC26A4 mutation than Mondini dysplasia patients. No FOXI1 or
      KCNJ10 potential pathogenic mutation was present, and GJB2 biallelic pathogenic
      mutations were uncommon (2.3%; 1/43). No significant correlation was observed
      between the genotype and phenotype of SLC26A4 mutations. CONCLUSION: SLC26A4
      accounts for 74.4% of inner ear malformations in our cohort, whereas FOXI1,
      KCNJ10, and GJB2 mutations are not common. Other possible genes or external
      factors may contribute to this multibranch abnormality.

PMID- 22412182
TI  - Stress prophylaxis in intensive care unit patients and the role of enteral
      nutrition.
AB  - Use of acid-suppressive therapy (AST) to prevent stress gastropathy in the
      intensive care unit has grown rapidly over the past 20 years. The primary
      indications for such use of AST include need for mechanical ventilation, overt
      gastrointestinal bleeding, severe burn, and head trauma. Despite this limited
      list of indications, proton pump inhibitors (PPIs) often are overprescribed for
      purposes of stress prophylaxis. Decreased mucosal blood flow with subsequent
      tissue ischemia is thought to be the mechanism responsible for stress-induced
      gastropathy. Subsequent activation of inflammatory and vasoconstrictive mediators
      determines the severity of the gastropathy. Numerous basic science studies
      suggest that enteral nutrition (EN) can improve mucosal blood flow and reverse
      the generation of these inflammatory mediators. Clinical studies evaluating the
      effectiveness of EN vs acid-suppressive medications, however, have shown variable
      results (and there are no randomized controlled trials to date). In
      hypersecretory states (such as head trauma and burns), AST should be given, even
      in patients who are tolerating EN. In the absence of a hypersecretory state,
      pharmacologic AST may be avoided or discontinued in patients who are tolerating
      EN. Stress prophylaxis medications also should be discontinued in patients who do
      not have a clear indication for their use. Overt bleeding in a patient receiving
      EN for stress prophylaxis should prompt the initiation of a PPI. Randomized
      controlled studies investigating the efficacy of EN for stress ulcer prophylaxis
      are needed. Protocols should be developed to alert healthcare teams to consider
      discontinuation of AST, especially when tolerance of EN is achieved.

PMID- 22412183
TI  - In vivo localization at the cellular level of stilbene fluorescence induced by
      Plasmopara viticola in grapevine leaves.
AB  - Accurate localization of phytoalexins is a key for better understanding their
      role. This work aims to localize stilbenes, the main phytoalexins of grapevine.
      The cellular localization of stilbene fluorescence induced by Plasmopara
      viticola, the agent of downy mildew, was determined in grapevine leaves of very
      susceptible, susceptible, and partially resistant genotypes during infection.
      Laser scanning confocal microscopy and microspectrofluorimetry were used to
      acquire UV-excited autofluorescence three-dimensional images and spectra of
      grapevine leaves 5-6 days after inoculation. This noninvasive technique of
      investigation in vivo was completed with in vitro spectrofluorimetric studies on
      pure stilbenes as their fluorescence is largely affected by the physicochemical
      environment in various leaf compartments. Viscosity was the major physicochemical
      factor influencing stilbene fluorescence intensity, modifying fluorescence yield
      by more than two orders of magnitude. Striking differences in the localization of
      stilbene fluorescence induced by P. viticola were observed between the different
      genotypes. All inoculated genotypes displayed stilbene fluorescence in cell walls
      of guard cells and periclinal cell walls of epidermal cells. Higher fluorescence
      intensity was observed in guard-cell walls than in any other compartment due to
      increased local viscosity. In addition stilbene fluorescence was found in
      epidermal cell vacuoles of the susceptible genotype and in the infected spongy
      parenchyma of the partially resistant genotype. The very susceptible genotype was
      devoid of fluorescence both in the epidermal vacuoles and the mesophyll. This
      strongly suggests that the resistance of grapevine leaves to P. viticola is
      correlated with the pattern of localization of induced stilbenes in host tissues.

PMID- 22412184
TI  - Overexpression of the AtLOS5 gene increased abscisic acid level and drought
      tolerance in transgenic cotton.
AB  - Drought is the major environmental stress that limits cotton (Gossypium hirsutum
      L.) production worldwide. LOS5/ABA3 (LOS5) encodes a molybdenum co-factor and is
      essential for activating aldehyde oxidase, which is involved in abscisic acid
      (ABA) biosynthesis. In this study, a LOS5 cDNA of Arabidopsis thaliana was
      overexpressed in cotton cultivar Zhongmiansuo35 (Z35) by Agrobacterium
      tumefaciens-mediated transformation. The transformation and overexpression of
      AtLOS5 were assessed by PCR and RT-PCR analysis. Detached shoots of transgenic
      cotton showed slower transpirational water loss than those of Z35. When pot-grown
      6-week-old seedlings were withheld from watering for 3 d, transgenic cotton
      accumulated 25% more endogenous ABA and about 20% more proline than Z35 plants.
      The transgenic plants also showed increased expression of some drought-responding
      genes such as P5CS and RD22, and enhanced activity of antioxidant enzymes such as
      superoxide dismutase, peroxidase, and ascorbate peroxidase. Their membrane
      integrity was considerably improved under water stress, as indicated by reduced
      malondialdehyde content and electrolyte leakage relative to control plants. When
      the pot-grown plants were subjected to deficit irrigation for 8 weeks (watering
      to 50% of field capacity), transgenic plants showed a 13% increase in fresh
      weight than the wild type under the same drought condition. These results suggest
      that the AtLOS5 transgenic cotton plants acquired a better drought tolerance
      through enhanced ABA production and ABA-induced physiological regulations.

PMID- 22412185
TI  - Stay-green in spring wheat can be determined by spectral reflectance measurements
      (normalized difference vegetation index) independently from phenology.
AB  - The green area displayed by a crop is a good indicator of its photosynthetic
      capacity, while chlorophyll retention or 'stay-green' is regarded as a key
      indicator of stress adaptation. Remote-sensing methods were tested to estimate
      these parameters in diverse wheat genotypes under different growing conditions.
      Two wheat populations (a diverse set of 294 advanced lines and a recombinant
      inbred line population of 169 sister lines derived from the cross between Seri
      and Babax) were grown in Mexico under three environments: drought, heat, and heat
      combined with drought. In the two populations studied here, a moderate heritable
      expression of stay-green was found-when the normalized difference vegetation
      index (NDVI) at physiological maturity was estimated using the regression of NDVI
      over time from the mid-stages of grain-filling to physiological maturity-and for
      the rate of senescence during the same period. Under heat and heat combined with
      drought environments, stay-green calculated as NDVI at physiological maturity and
      the rate of senescence, showed positive and negative correlations with yield,
      respectively. Moreover, stay-green calculated as an estimation of NDVI at
      physiological maturity and the rate of senescence regressed on degree days give
      an independent measurement of stay-green without the confounding effect of
      phenology. On average, in both populations under heat and heat combined with
      drought environments CTgf and stay-green variables accounted for around 30% of
      yield variability in multiple regression analysis. It is concluded that stay
      green traits may provide cumulative effects, together with other traits, to
      improve adaptation under stress further.

PMID- 22412186
TI  - D-type cyclins control cell division and developmental rate during Arabidopsis
      seed development.
AB  - Seed development in Arabidopsis is characterized by stereotypical division
      patterns, suggesting that coordinated control of cell cycle may be required for
      correct patterning and growth of the embryo and endosperm. D-type cyclins (CYCD)
      are key cell cycle regulators with roles in developmental processes, but
      knowledge regarding their involvement in seed development remains limited. Here,
      a family-wide gene expression, and loss- and gain-of-function approach was
      adopted to reveal additional functions for CYCDs in the development of seed
      tissues. CYCD genes have both discrete and overlapping tissue-specific expression
      patterns in the seed as revealed by GUS reporter gene expression. Analysis of
      different mutant combinations revealed that correct CYCD levels are required in
      seed development. The CYCD3 subgroup is specifically required as its loss caused
      delayed development, whereas overexpression in the embryo and endosperm of
      CYCD3;1 or a previously uncharacterized gene, CYCD7;1, variously leads to induced
      proliferation, abnormal phenotypes, and elevated seed abortion. CYCD3;1
      overexpression provoked a delay in embryonic developmental progression and
      abnormalities including additional divisions of the hypophysis and suspensor,
      regions where CYCD3 genes are normally expressed, but did not affect endosperm
      development. Overexpression of CYCD7;1, not normally expressed in seed
      development, promoted overgrowth of both embryo and endosperm through increased
      division and cell enlargement. In contrast to post-germination growth, where
      pattern and organ size is not generally related to division, results suggest that
      a close control of cell division through regulation of CYCD activity is important
      during seed development in conferring both developmental rate and correct
      patterning.

PMID- 22412187
TI  - Seven zinc-finger transcription factors are novel regulators of the stress
      responsive gene OsDREB1B.
AB  - Plants have evolved several mechanisms in order to cope with adverse
      environmental conditions. The transcription factors (TFs) belonging to the
      DREB1/CBF subfamily have been described as major regulators of the plant
      responses to different abiotic stresses. This study focused on the rice gene
      OsDREB1B, initially described as highly and specifically induced by cold.
      However, here it is shown that OsDREB1B is not only induced by low temperatures,
      but also by drought and mechanical stress. In order to identify novel TFs that
      bind to its promoter, a yeast one-hybrid system was used to screen a cold-induced
      cDNA expression library. Thereby seven novel Zn-finger TFs were identified that
      bind to the promoter of OsDREB1B. Among them, there were four Zn-finger
      homeodomain (ZF-HD) and three C(2)H(2)-type Zn-finger TFs. Gene expression
      studies showed that these TFs are differentially regulated at transcriptional
      level by different abiotic stress conditions, which is illustrative of the
      crosstalk between stress signalling pathways. Protein-protein interaction studies
      revealed the formation of homo- and heterodimers among the ZF-HD TFs identified,
      but not for the C(2)H(2)-type. Using a transactivation assay in Arabidopsis
      protoplasts, all the TFs identified repressed the expression of the reporter
      gene, driven by the promoter of OsDREB1B. This assay also showed that the
      dimerization observed between the ZF-HD TFs may play a role on their
      transactivation activity. The results here presented suggest a prominent role of
      Zn-finger TFs in the regulation of OsDREB1B.

PMID- 22412188
TI  - A role for cytoskeletal protein acetylation in modulating myometrial activity.
AB  - Posttranslational modifications (PTMs) of proteins by phosphorylation are a well
      established mechanism by which their activities can be regulated to affect
      cellular physiology. However, it is becoming increasingly evident that PTMs of
      proteins by acetylation of lysine residues is also a key effecter in regulating
      their functional abilities. The best characterized case of this is the epigenetic
      effects of histone acetyltransferases and deacetylases on gene expression via
      modulation of nuclear histone acetylation and chromatin remodeling. However,
      recent published evidence now strongly implicates an important role for
      nonhistone acetylation in regulating cellular function. In this review, we have
      considered the potential for regulating myometrial activity not only by
      epigenetic mechanisms but also by nonepigenetic protein acetylation processes
      that could directly affect the contractile machinery within these smooth muscle
      cells.

PMID- 22412189
TI  - The effect of citalopram on midbrain CRF receptors 1 and 2 in a primate model of
      stress-induced amenorrhea.
AB  - We have demonstrated marked differences in the neurobiology of the serotonin
      system between stress-sensitive (SS) and stress-resilient (SR) cynomolgus
      macaques characterized in a model of stress-induced amenorrhea, also called
      functional hypothalamic amenorrhea (FHA). Dysfunction of the serotonin system in
      SS monkeys suggested that administration of a selective serotonin reuptake
      inhibitor (SSRI) might correct FHA. This study examines the effect of
      escitalopram (CIT) administration to SS and SR monkeys on corticotrophin
      releasing factor (CRF) receptor 1 (CRF-R1) and CRF receptor 2 (CRF-R2) gene
      expression in the serotonin cell body region of the midbrain dorsal raphe. CRF-R1
      was not significantly different between groups. There was a significant effect of
      treatment and a significant interaction between treatment and stress sensitivity
      on the average CRF-R2-positive pixel area (P < .004 and P < .006, respectively)
      and on the average number of CRF-R2-positive cells (P < .023 and P < .025,
      respectively). CIT significantly increased CRF-R2-positive pixel area and cell
      number in the SS group (pixel area P < .001; cell number P < .01; Bonferoni) but
      not in the SR group. In summary, CIT administration tended to decrease CRF-R1,
      but the small animal number precluded significance. CIT administration
      significantly increased CRF-R2 only in SS animals. These data suggest that the
      administration of CIT reduces anxiogenic components and increases anxiolytic
      components of the CRF system in the midbrain serotonin network, which in turn
      leads to improved ovarian function. Moreover, these data raise the possibility
      that SSRIs may be effective in the treatment of stress-induced infertility.

PMID- 22412190
TI  - Selective disruption of high sensitivity heat activation but not capsaicin
      activation of TRPV1 channels by pore turret mutations.
AB  - The capsaicin receptor transient receptor potential vanilloid (TRPV)1 is a highly
      heat-sensitive ion channel. Although chemical activation and heat activation of
      TRPV1 elicit similar pungent, painful sensation, the molecular mechanism
      underlying synergistic activation remains mysterious. In particular, where the
      temperature sensor is located and whether heat and capsaicin share a common
      activation pathway are debated. To address these fundamental issues, we searched
      for channel mutations that selectively affected one form of activation. We found
      that deletion of the first 10 amino acids of the pore turret significantly
      reduced the heat response amplitude and shifted the heat activation threshold,
      whereas capsaicin activation remained unchanged. Removing larger portions of the
      turret disrupted channel function. Introducing an artificial sequence to replace
      the deleted region restored sensitive capsaicin activation in these nonfunctional
      channels. The heat activation, however, remained significantly impaired, with the
      current exhibiting diminishing heat sensitivity to a level indistinguishable from
      that of a voltage-gated potassium channel, Kv7.4. Our results demonstrate that
      heat and capsaicin activation of TRPV1 are structurally and mechanistically
      distinct processes, and the pore turret is an indispensible channel structure
      involved in the heat activation process but is not part of the capsaicin
      activation pathway. Synergistic effect of heat and capsaicin on TRPV1 activation
      may originate from convergence of the two pathways on a common activation gate.

PMID- 22412191
TI  - The voltage dependence of the TMEM16B/anoctamin2 calcium-activated chloride
      channel is modified by mutations in the first putative intracellular loop.
AB  - Ca(2+)-activated Cl(-) channels (CaCCs) are involved in several physiological
      processes. Recently, TMEM16A/anoctamin1 and TMEM16B/anoctamin2 have been shown to
      function as CaCCs, but very little information is available on the structure
      function relations of these channels. TMEM16B is expressed in the cilia of
      olfactory sensory neurons, in microvilli of vomeronasal sensory neurons, and in
      the synaptic terminals of retinal photoreceptors. Here, we have performed the
      first site-directed mutagenesis study on TMEM16B to understand the molecular
      mechanisms of voltage and Ca(2+) dependence. We have mutated amino acids in the
      first putative intracellular loop and measured the properties of the wild-type
      and mutant TMEM16B channels expressed in HEK 293T cells using the whole cell
      voltage-clamp technique in the presence of various intracellular Ca(2+)
      concentrations. We mutated E367 into glutamine or deleted the five consecutive
      glutamates (386)EEEEE(390) and (399)EYE(401). The EYE deletion did not
      significantly modify the apparent Ca(2+) dependence nor the voltage dependence of
      channel activation. E367Q and deletion of the five glutamates did not greatly
      affect the apparent Ca(2+) affinity but modified the voltage dependence, shifting
      the conductance-voltage relations toward more positive voltages. These findings
      indicate that glutamates E367 and (386)EEEEE(390) in the first intracellular
      putative loop play an important role in the voltage dependence of TMEM16B, thus
      providing an initial structure-function study for this channel.

PMID- 22412192
TI  - NLRC5 deficiency selectively impairs MHC class I- dependent lymphocyte killing by
      cytotoxic T cells.
AB  - Nucleotide-binding oligomerization domain-like receptors (NLRs) are intracellular
      proteins involved in innate-driven inflammatory responses. The function of the
      family member NLR caspase recruitment domain containing protein 5 (NLRC5) remains
      a matter of debate, particularly with respect to NF-kappaB activation, type I
      IFN, and MHC I expression. To address the role of NLRC5, we generated Nlrc5
      deficient mice (Nlrc5(Delta/Delta)). In this article we show that these animals
      exhibit slightly decreased CD8(+) T cell percentages, a phenotype compatible with
      deregulated MHC I expression. Of interest, NLRC5 ablation only mildly affected
      MHC I expression on APCs and, accordingly, Nlrc5(Delta/Delta) macrophages
      efficiently primed CD8(+) T cells. In contrast, NLRC5 deficiency dramatically
      impaired basal expression of MHC I in T, NKT, and NK lymphocytes. NLRC5 was
      sufficient to induce MHC I expression in a human lymphoid cell line, requiring
      both caspase recruitment and LRR domains. Moreover, endogenous NLRC5 localized to
      the nucleus and occupied the proximal promoter region of H-2 genes. Consistent
      with downregulated MHC I expression, the elimination of Nlrc5(Delta/Delta)
      lymphocytes by cytotoxic T cells was markedly reduced and, in addition, we
      observed low NLRC5 expression in several murine and human lymphoid-derived tumor
      cell lines. Hence, loss of NLRC5 expression represents an advantage for evading
      CD8(+) T cell-mediated elimination by downmodulation of MHC I levels-a mechanism
      that may be exploited by transformed cells. Our data show that NLRC5 acts as a
      key transcriptional regulator of MHC I in lymphocytes and support an essential
      role for NLRs in directing not only innate but also adaptive immune responses.

PMID- 22412193
TI  - Prostaglandin E(2) produced by the lung augments the effector phase of allergic
      inflammation.
AB  - Elevated PGE(2) is a hallmark of most inflammatory lesions. This lipid mediator
      can induce the cardinal signs of inflammation, and the beneficial actions of
      nonsteroidal anti-inflammatory drugs are attributed to inhibition of
      cyclooxygenase (COX)-1 and COX-2, enzymes essential in the biosynthesis of PGE(2)
      from arachidonic acid. However, both clinical studies and rodent models suggest
      that, in the asthmatic lung, PGE(2) acts to restrain the immune response and
      limit physiological change secondary to inflammation. To directly address the
      role of PGE(2) in the lung, we examined the development of disease in mice
      lacking microsomal PGE(2) synthase-1 (mPGES1), which converts COX-1/COX-2-derived
      PGH(2) to PGE(2). We show that mPGES1 determines PGE(2) levels in the naive lung
      and is required for increases in PGE(2) after OVA-induced allergy. Although loss
      of either COX-1 or COX-2 increases the disease severity, surprisingly, mPGES1(-/
      ) mice show reduced inflammation. However, an increase in serum IgE is still
      observed in the mPGES1(-/-) mice, suggesting that loss of PGE(2) does not impair
      induction of a Th2 response. Furthermore, mPGES1(-/-) mice expressing a
      transgenic OVA-specific TCR are also protected, indicating that PGE(2) acts
      primarily after challenge with inhaled Ag. PGE(2) produced by the lung plays the
      critical role in this response, as loss of lung mPGES1 is sufficient to protect
      against disease. Together, this supports a model in which mPGES1-dependent PGE(2)
      produced by populations of cells native to the lung contributes to the effector
      phase of some allergic responses.

PMID- 22412194
TI  - Role of gammadelta T cells in alpha-galactosylceramide-mediated immunity.
AB  - Attempts to harness mouse type I NKT cells in different therapeutic settings
      including cancer, infection, and autoimmunity have proven fruitful using the CD1d
      binding glycolipid alpha-galactosylceramide (alpha-GalCer). In these different
      models, the effects of alpha-GalCer mainly relied on the establishment of a type
      I NKT cell-dependent immune cascade involving dendritic cell, NK cell, B cell, or
      conventional CD4(+) and CD8(+) T cell activation/regulation as well as
      immunomodulatory cytokine production. In this study, we showed that gammadelta T
      cells, another population of innate-like T lymphocytes, displayed a phenotype of
      activated cells (cytokine production and cytotoxic properties) and were required
      to achieve an optimal alpha-GalCer-induced immune response. Using gene-targeted
      mice and recombinant cytokines, a critical need for IL-12 and IL-18 has been
      shown in the alpha-GalCer-induced IFN-gamma production by gammadelta T cells.
      Moreover, this cytokine production occurred downstream of type I NKT cell
      response, suggesting their bystander effect on gammadelta T cells. In line with
      this, gammadelta T cells failed to directly recognize the CD1d/alpha-GalCer
      complex. We also provided evidence that gammadelta T cells increase their
      cytotoxic properties after alpha-GalCer injection, resulting in an increase in
      killing of tumor cell targets. Moreover, using cancer models, we demonstrated
      that gammadelta T cells were required for an optimal alpha-GalCer-mediated anti
      tumor activity. Finally, we reported that immunization of wild-type mice with
      alpha-GalCer enhanced the adaptive immune response elicited by OVA, and this
      effect was strongly mediated by gammadelta T cells. We conclude that gammadelta T
      cells amplify the innate and acquired response to alpha-GalCer, with possibly
      important outcomes for the therapeutic effects of this compound.

PMID- 22412196
TI  - Regulation of proinflammatory Th17 responses during Trypanosoma cruzi infection
      by IL-12 family cytokines.
AB  - Previously, we reported that the transcription factor T-bet (Tbx21) regulates
      Th17 responses to Trypanosoma cruzi infection in an IFN-gamma-independent manner.
      In an effort to further understand this regulation, we examined the development
      and plasticity of Th17 cells during T. cruzi infection. Th17 cells recovered from
      infected Tbx21(-/-) mice were amenable to the inhibitory effects of T-bet, as
      ectopic expression of T-bet reduced IL-17 expression. We subsequently addressed
      the role of IL-12 family cytokines IL-12 and IL-27 and report that IL-12p35(-/-)
      mice infected with T. cruzi exhibited a significant increase in Th17 cells and
      Th17-associated inflammation. Ex vivo culture of these cells with IL-12 led to a
      dramatic reduction in IL-17 production and concomitant increase in IFN-gamma.
      Importantly, the ability of IL-12 to suppress IL-17 was independent of IFN-gamma.
      Surprisingly, and contrary to results reported for other pathogens, IL-27 had no
      inhibitory effect on Th17 development, as Ebi-3(-/-) mice failed to show any
      increase in their T. cruzi-specific Th17 response. Furthermore, IL-27 could not
      compensate or synergize with IL-12 to suppress IL-17 production ex vivo. Thus, we
      have established that IL-12, not IL-27, is critical for regulating Th17 responses
      to T. cruzi.

PMID- 22412197
TI  - Marginal zone B cells regulate antigen-specific T cell responses during
      infection.
AB  - Marginal zone B cells (MZB) participate in the early immune response to several
      pathogens. In this study, we show that in MUMT mice infected with Leishmania
      donovani, CD8 T cells displayed a greater cytotoxic potential and generated more
      effector memory cells compared with infected wild type mice. The frequency of
      parasite-specific, IFN-gamma(+) CD4 T cells was also increased in MUMT mice. B
      cells were able to capture parasites, which was associated with upregulation of
      surface IgM and MyD88-dependent IL-10 production. Moreover, MZB presented
      parasite Ags to CD4 T cells in vitro. Depletion of MZB also enhanced T cell
      responses and led to a decrease in the parasite burden but did not alter the
      generation of effector memory T cells. Thus, MZB appear to suppress protective T
      cell responses during the early stages of L. donovani infection.

PMID- 22412195
TI  - Ethanol induces oxidative stress in alveolar macrophages via upregulation of
      NADPH oxidases.
AB  - Chronic alcohol abuse is a comorbid variable of acute respiratory distress
      syndrome. Previous studies showed that, in the lung, chronic alcohol consumption
      increased oxidative stress and impaired alveolar macrophage (AM) function. NADPH
      oxidases (Noxes) are the main source of reactive oxygen species in AMs.
      Therefore, we hypothesized that chronic alcohol consumption increases AM oxidant
      stress through modulation of Nox1, Nox2, and Nox4 expression. AMs were isolated
      from male C57BL/6J mice, aged 8-10 wk, which were treated with or without ethanol
      in drinking water (20% w/v, 12 wk). MH-S cells, a mouse AM cell line, were
      treated with or without ethanol (0.08%, 3 d) for in vitro studies. Selected cells
      were treated with apocynin (300 MUM), a Nox1 and Nox2 complex formation
      inhibitor, or were transfected with Nox small interfering RNAs (20-35 nM), before
      ethanol exposure. Human AMs were isolated from alcoholic and control patients'
      bronchoalveolar lavage fluid. Nox mRNA levels (quantitative RT-PCR), protein
      levels (Western blot and immunostaining), oxidative stress (2',7'
      dichlorofluorescein-diacetate and Amplex Red analysis), and phagocytosis
      (Staphylococcus aureus internalization) were measured. Chronic alcohol increased
      Nox expression and oxidative stress in mouse AMs in vivo and in vitro.
      Experiments using apocynin and Nox small interfering RNAs demonstrated that
      ethanol-induced Nox4 expression, oxidative stress, and AM dysfunction were
      modulated through Nox1 and Nox2 upregulation. Further, Nox1, Nox2, and Nox4
      protein levels were augmented in human AMs from alcoholic patients compared with
      control subjects. Ethanol induces AM oxidative stress initially through
      upregulation of Nox1 and Nox2 with downstream Nox4 upregulation and subsequent
      impairment of AM function.

PMID- 22412199
TI  - LAPTM4B polymorphisms is associated with ovarian cancer susceptibility and its
      prognosis.
AB  - OBJECTIVE: Lysosome-associated protein transmembrane 4 beta (LAPTM4B) is an
      important novel gene associated with the proliferation and differentiation of
      cells. Recent studies have shown that it was overexpressed in many cancer
      tissues. This study investigated the association between different LAPTM4B
      polymorphisms and the susceptibility and prognosis of ovarian cancer. METHODS: A
      case-control study was performed in 282 patients with ovarian cancer and 365
      control subjects. Genomic DNA was extracted from peripheral blood lymphocytes in
      all participants. LAPTM4B genotypes were determined using polymerase chain
      reaction. RESULTS: There was a significantly higher LAPTM4B 2 allele frequency in
      ovarian cancer cases than controls (P < 0.05). Using the LAPTM4B 1/1 genotype as
      the reference, we found that the LAPTM4B 1/2 and LAPTM4B 2/2 genotypes were
      positively associated with ovarian cancer. Additionally, we found a negative
      correlation between the tumor grade and LAPTM4B allele genotype, which indicates
      strongly that LAPTM4B 2 could affect the survival of patients. CONCLUSIONS: These
      findings indicate that the LAPTM4B 2 allele may be a risk factor for ovarian
      cancer and may play an important role in genetic susceptibility to ovarian
      cancer.

PMID- 22412200
TI  - Dramatic need for cooperation and advocacy within the academy and beyond.

PMID- 22412198
TI  - The role of tuberous sclerosis complex 1 in regulating innate immunity.
AB  - The mechanisms that control TLR-induced responses, including endotoxin tolerance,
      have been not well understood. The tuberous sclerosis complex 1 (TSC1) is a tumor
      suppressor that inhibits the mammalian target of rapamycin (mTOR). We show in
      this study that deficiency of TSC1 results in enhanced activation of not only
      mTOR complex 1 (mTORC1), but also JNK1/2, following LPS stimulation in
      macrophages. TSC1-deficient macrophages produce elevated proinflammatory
      cytokines and NO in response to multiple TLR ligands. Such enhanced TLR-induced
      responses can be inhibited by reducing mTORC1 and JNK1/2 activities with chemical
      inhibitors or small hairpin RNA, suggesting that TSC1 negatively controls TLR
      responses through both mTORC1 and JNK1/2. The impact of TSC1 deficiency appeared
      not limited to TLRs, as NOD- and RIG-I/MDA-5-induced innate responses were also
      altered in TSC1-deficient macrophages. Furthermore, TSC1 deficiency appears to
      cause impaired induction of endotoxin tolerance in vitro and in vivo, which is
      correlated with increased JNK1/2 activation and can be reversed by JNK1/2
      inhibition. Our results reveal a critical role of TSC1 in regulating innate
      immunity by negative control of mTORC1 and JNK1/2 activation.

PMID- 22412201
TI  - Making "health in all policies" a reality requires you!

PMID- 22412202
TI  - Impact of a faculty orientation and development committee.
AB  - This paper describes the faculty enrichment activities and outcomes of a faculty
      orientation and development committee at a college of pharmacy. The committee
      used a continuous quality improvement (CQI) framework that included needs
      assessment, planning and implementation of programs and workshops, assessment of
      activities, and evaluation of feedback to improve future programming. Some of the
      programs established by the committee include a 3-month orientation process for
      new hires and development workshops on a broad range of topics including
      scholarship (eg, research methods), teaching (eg, test-item writing), and general
      development (mentorship). Evidence of the committee's success is reflected by
      high levels of faculty attendance at workshops, positive feedback on workshop
      evaluations, and overall high levels of satisfaction with activities. The
      committee has served as a role model for improving faculty orientation and
      retention.

PMID- 22412203
TI  - Pharmacy faculty retirement at colleges and schools of pharmacy in the United
      States and Canada.
AB  - OBJECTIVES: To examine the work-related activities of full-time faculty members
      55 years of age and older; to describe the retirement plans and perceptions of
      these faculty members; and to examine the factors, perceptions, or conditions
      that might influence the retirement decision. METHODS: Pharmacy faculty members
      aged 55 years and older in the United States and Canada were invited to
      participate in an online survey regarding their perceptions on issues related to
      their retirement planning behavior. RESULTS: Four hundred eighty-eight faculty
      members completed the survey instrument. The typical respondent worked 50 hours
      per week on work-related activities, was active in teaching and service, and had
      published an average of 5 refereed papers during the previous 36 months. The
      number of articles published was positively related to the respondent's target
      retirement age. The average anticipated retirement age was 66.6 years, and most
      respondents participated in a defined benefit plan. The majority would revise
      their target retirement age downwards if conditions were favorable. CONCLUSION:
      The primary factors that influence the pharmacy faculty retirement decision
      include financial status, academic productivity, and higher order needs such as
      the opportunity to participate in meaningful activities. These findings can be
      used by administrators in strategic planning related to attracting and retaining
      quality faculty members.

PMID- 22412204
TI  - Pharmacy students' views of faculty feedback on academic performance.
AB  - OBJECTIVE: To investigate students' views on and satisfaction with faculty
      feedback on their academic performance. METHODS: A 41-item survey instrument was
      developed based on a literature review relating to effective feedback. All
      pharmacy undergraduate students were invited via e-mail to complete the self
      administered electronic questionnaire relating to their views on feedback,
      including faculty feedback received to date regarding their academic performance.
      RESULTS: A response rate of 61% (343/561) was obtained. Only 32.3% of students
      (107/331) agreed that they were satisfied with the feedback they received;
      dissatisfaction with examination feedback was particularly high. The provision of
      faculty feedback was perceived to be variable in terms of quality and quantity.
      CONCLUSIONS: There are some inconsistencies relating to provision of feedback
      within the MPharm degree program at Queen's University Belfast. Further work is
      needed to close the gap between student expectations and the faculty's delivery
      of feedback on academic performance.

PMID- 22412205
TI  - Concurrent use of an audience response system at a multi-campus college of
      pharmacy.
AB  - OBJECTIVE: To assess the impact of an audience response system (ARS) on student
      engagement at a multi-campus college of pharmacy. METHODS: An online
      questionnaire was designed and administered to measure the impact of an ARS on
      student engagement, distance education, projected use, and satisfaction among
      pharmacy students for a course delivered across 3 sites via synchronous video
      transmission. RESULTS: Students reported that use of the ARS made it easier to
      participate (85.3%) and helped them to focus (75.7%) in classes when the lecturer
      was physically at a different site. They also valued that the ARS allowed them to
      respond anonymously (93.2%). A minority of students indicated that use of the ARS
      was distracting (11.8%). CONCLUSIONS: Implementation of an ARS was associated
      with positive student perceptions of engagement and may improve feelings of
      connectedness among students at schools with multiple sites. Use of ARSs could
      also represent a cognitive intercession strategy to help reduce communication
      apprehension.

PMID- 22412206
TI  - Multi-institutional study of women and underrepresented minority faculty members
      in academic pharmacy.
AB  - OBJECTIVES: To examine trends in the numbers of women and underrepresented
      minority (URM) pharmacy faculty members over the last 20 years, and determine
      factors influencing women faculty members' pursuit and retention of an academic
      pharmacy career. METHODS: Twenty-year trends in women and URM pharmacy faculty
      representation were examined. Women faculty members from 9 public colleges and
      schools of pharmacy were surveyed regarding demographics, job satisfaction, and
      their academic pharmacy career, and relationships between demographics and
      satisfaction were analyzed. RESULTS: The number of women faculty members more
      than doubled between 1989 and 2009 (from 20.7% to 45.5%), while the number of URM
      pharmacy faculty members increased only slightly over the same time period. One
      hundred fifteen women faculty members completed the survey instrument and
      indicated they were generally satisfied with their jobs. The academic rank of
      professor, being a nonpharmacy practice faculty member, being tenured/tenure
      track, and having children were associated with significantly lower satisfaction
      with fringe benefits. Women faculty members who were tempted to leave academia
      for other pharmacy sectors had significantly lower salary satisfaction and
      overall job satisfaction, and were more likely to indicate their expectations of
      academia did not match their experiences (p<0.05). CONCLUSIONS: The significant
      increase in the number of women pharmacy faculty members over the last 20 years
      may be due to the increased number of female pharmacy graduates and to women
      faculty members' satisfaction with their careers. Lessons learned through this
      multi-institutional study and review may be applicable to initiatives to improve
      recruitment and retention of URM pharmacy faculty members.

PMID- 22412207
TI  - Pharmacy student absenteeism and academic performance.
AB  - OBJECTIVES: To assess the association of pharmacy students' personal
      characteristics with absenteeism and academic performance. METHODS: A survey
      instrument was distributed to first- (P1) and second-year (P2) pharmacy students
      to gather characteristics including employment status, travel time to school, and
      primary source of educational funding. In addition, absences from specific
      courses and reasons for not attending classes were assessed. Participants were
      divided into "high" and "low" performers based on grade point average. RESULTS:
      One hundred sixty survey instruments were completed and 135 (84.3%) were included
      in the study analysis. Low performers were significantly more likely than high
      performers to have missed more than 8 hours in therapeutics courses. Low
      performers were significantly more likely than high performers to miss class when
      the class was held before or after an examination and low performers were
      significantly more likely to believe that participating in class did not benefit
      them. CONCLUSIONS: There was a negative association between the number of hours
      students' missed and their performance in specific courses. These findings
      provide further insight into the reasons for students' absenteeism in a college
      or school of pharmacy setting.

PMID- 22412208
TI  - Impact of a workshop about aging on the empathy scores of pharmacy and medical
      students.
AB  - OBJECTIVE: To measure changes in pharmacy and medical students' empathy scores
      after a 40-minute workshop during which students observed and discussed a
      theatrical performance about the challenges of aging. METHODS: First-year
      pharmacy and medical students (n = 187 and n = 183, respectively) participating
      in the workshop observed and discussed a 10-minute performance in which students
      enacted problems and concerns faced by elderly patients. The Jefferson Scale of
      Empathy (JSE) was administered just prior to the workshop (pretest), immediately
      afterward (posttest 1), and 7 or 26 days afterward (posttest 2). RESULTS: Empathy
      increased significantly from pretest to posttest 1 for students of each
      profession (p <0.01). Improvement in empathy scores declined by the time the JSE
      was readministered to pharmacy students 7 days later and to medical students 26
      days later (posttest 2). Similar patterns of improved and declining empathy were
      found when the data were analyzed by gender and medical student specialty
      interest (ie, primary vs non-primary care specialties). CONCLUSION: Empathy
      scores increased but were not sustained for both pharmacy and medical students
      after a brief workshop on aging that required limited personnel resources.

PMID- 22412209
TI  - Development and pilot testing of a multiple mini-interview for admission to a
      pharmacy degree program.
AB  - OBJECTIVES: To develop and pilot test a multiple mini-interview (MMI) to select
      students for admission to a pharmacy degree program. METHODS: A nominal group
      process was used to identify 8 important nonacademic attributes of pharmacists,
      with relative importance determined by means of a paired-comparison survey of
      pharmacy stakeholders (ie, university-affiliated individuals with a vested
      interest in the quality of student admitted to the pharmacy program, such as
      faculty members, students, admissions staff members, and practitioners). A 10
      station MMI based on the weighted-attribute blueprint was pilot tested with 30
      incoming pharmacy students. MMI score reliability (intraclass correlation
      coefficient [ICC]) and correlation with other admissions tool scores were
      determined. RESULTS: Station scores provided by student interviewers were
      slightly higher than those of faculty member or practitioner interviewers. While
      most interviewers judged a 6-minute interview as "just right" and an 8-minute
      interview "a bit long," candidates had the opposite opinion. Station scenarios
      had face validity for candidates and interviewers. The ICC for the MMI was 0.77
      and correlations with prepharmacy average (PPA) and Pharmacy College Admission
      Test (PCAT) composite were negligible. CONCLUSIONS: MMI feasibility was
      confirmed, based on the finding that interview scores were reliable and that this
      admissions tool measures different attributes than do the PCAT and PPA.

PMID- 22412210
TI  - Second-year pharmacy students' perceptions of adhering to a complex simulated
      medication regimen.
AB  - OBJECTIVE: To conduct a simulated medication regimen with second-year pharmacy
      students to determine their anticipated versus actual difficulty in adhering to
      it. METHODS: Second-year pharmacy students were given 6 fictitious medications
      (jellybeans) and a drug regimen to adhere to for 6 days. Pre- and post
      intervention surveys were conducted to compare participants anticipated vs.
      actual difficulty with adherence and changes in empathy toward patients. RESULTS:
      The 69 (96%) students who participated in the study missed on average 16% of all
      simulated medication doses and noted that adhering to the complex medication
      regimen was more difficult than they had anticipated. Eighty-nine percent of
      students agreed or strongly agreed the project was valuable in developing empathy
      towards patients taking complex medication regimens. CONCLUSIONS: Pharmacy
      students participating in a simulated medication regimen missed a notable number
      of doses and reported a greater level of empathy for patients taking complex
      medication regiments. Finding meaningful ways to integrate adherence into the
      curriculum is essential.

PMID- 22412211
TI  - The Assessment, Development, Assurance Pharmacist's Tool (ADAPT) for ensuring
      quality implementation of health promotion programs.
AB  - OBJECTIVE: To develop and validate the Assessment, Development, Assurance
      Pharmacist's Tool (ADAPT), an instrument for pharmacists and student pharmacists
      to use in developing and implementing health promotion programs. METHODS: The 36
      item ADAPT instrument was developed using the framework of public health's 3 core
      functions (assessment, policy development, and assurance) and 10 essential
      services. The tool's content and usage was assessed and conducted through peer
      review and initial validity testing processes. RESULTS: Over 20 faculty members,
      preceptors, and student pharmacists at 5 institutions involved in planning and
      implementing health promotion initiatives reviewed the instrument and conducted
      validity testing. The instrument took approximately 15 minutes to complete and
      the findings resulted in changes and improvements to elements of the programs
      evaluated. CONCLUSION: The ADAPT instrument fills a need to more effectively
      plan, develop, implement, and evaluate pharmacist-directed public health programs
      that are evidence-based, high-quality, and compliant with laws and regulations
      and facilitates documentation of pharmacists' contributions to public health.

PMID- 22412212
TI  - A diabetes self-management education class taught by pharmacy students.
AB  - OBJECTIVE: To assess the impact of pharmacy students teaching a diabetes self
      management education (DSME) class on their competence and confidence in providing
      diabetes education. DESIGN: Pharmacy students enrolled in a service-learning
      elective first observed pharmacy faculty members teaching a DSME class and then 4
      weeks later organized and taught a DSME class to a different group of patients at
      a student-run free medical clinic. ASSESSMENT: Student performance as assessed by
      faculty members using a rubric was above average, with a mean score of 3.3 on a
      4.0 scale. Overall, student confidence after teaching the group DSME class was
      significantly higher than before teaching the class. CONCLUSION: Organizing and
      teaching a DSME class improved third-year pharmacy students' confidence and
      diabetes knowledge and skills, as well as provided a valuable service to patients
      at a free medical clinic.

PMID- 22412213
TI  - Integration of physical assessment within a pathophysiology course for pharmacy.
AB  - OBJECTIVE: To determine first-year pharmacy students' analysis, confidence, and
      knowledge of patient physical assessment integrated within a pathophysiology
      curriculum. DESIGN: A prospective quasi-experimental study using validated pre-
      and post-surveys and follow-up examinations was conducted to objectively assess
      the confidence and knowledge of pharmacy students' physical assessment skills.
      ASSESSMENT: Students' perceived ability to perform physical assessment techniques
      improved. Topic mastery was demonstrated by a final comprehensive examination
      with a composite student class score of 83%. CONCLUSION: First-year pharmacy
      students demonstrated acquisition of patient physical assessment skills when
      integrated into a pathophysiology course.

PMID- 22412214
TI  - A 1-day course to improve the teaching effectiveness of health professions
      faculty members.
AB  - OBJECTIVE: To determine the effect of a 1-day teaching-methods course for
      pharmacy and nursing faculty members on teaching proficiency and perceptions of
      effective teaching. DESIGN: A 1-day teaching-methods course was created and
      presented to 12 pharmacy and nursing faculty members. Participants' teaching
      sessions were video-recorded pre- and post-course. ASSESSMENT: A panel of
      educators evaluated pre- and post-course video-recorded teaching presentations to
      assess teaching effectiveness. Participants completed pre- and post-course self
      evaluations and surveys. Panelists' assessments confirmed significant improvement
      in 7 of 10 domains. Perceptions of teaching efficacy and proficiency to teach
      effectively improved after completion of the course. CONCLUSION: A 1-day teaching
      methods course, requiring minimal resources, is a valuable development resource
      that can improve teaching effectiveness through enhanced communication and
      teaching techniques. Because effective teaching is positively correlated with
      students' learning, training seminars can be integral to comprehensive quality
      improvement.

PMID- 22412215
TI  - A mnemonic for pharmacy students to use in pharmacotherapy assessment.
AB  - OBJECTIVE: To introduce pharmacy students to a patient-centered mnemonic to aid
      them in remembering the most important parameters when assessing a patient's drug
      therapy and to determine whether use of the device improved students' clinical
      examination scores. DESIGN: Second-year pharmacy students were randomized to an
      intervention group or a control group. A 30-minute presentation on the rationale
      of the mnemonic and how to apply it to clinical scenarios was given to the
      intervention group and then a case-based multiple-choice clinical examination was
      administered. Students in the control group completed the same examination first
      and then were given the mnemonic. ASSESSMENT: Ninety-five students completed the
      examination. Examination scores of students in the intervention group were 6%
      higher than those of students in the control group (p = 0.04). A 6-question
      survey instrument was administered to both groups and the majority of students
      agreed that they would use the mnemonic when assessing patients during their
      upcoming practice experiences. One-hundred percent of the students stated that
      the mnemonic definitely or probably helped them (or would have helped them) think
      critically when assessing the patient cases. CONCLUSIONS: Pharmacy students who
      used a mnemonic device for pharmacotherapy assessment exhibited better decision
      making skills and made fewer errors than students who did not use the mnemonic.

PMID- 22412216
TI  - From the bayous to the sand dunes: one faculty member's year abroad as a
      Fulbright Scholar.

PMID- 22412217
TI  - Effect of sintering conditions on the magnetic and microstructural properties of
      Nd-Fe-B sintered magnets doped with DyF(3) powders.
AB  - The microstructural and magnetic property changes of DyF(3)-doped (Nd(26.06),
      Dy(6.51))-Fe(bal) -B(0.97)-M(2.39) (wt. %) (M = Cu, Al, Co, and Nb) sintered
      magnets as functions of the sintering conditions were studied. The sintering
      conditions for the optimum core-shell microstructure were determined. When the
      magnets were sintered at 1050  degrees C for 4 h, a coercivity of 35.1 kOe was
      obtained without sacrificing the remanence. When the magnets were doped with
      DyF(3), the formation of the RE-rich phase (Nd-Dy-O) was effectively suppressed
      and, hence, saving the Dy. In addition, the formation of a cubic-NdOF triple
      junction phase (TJP) improves the interface uniformity and enhances the
      coercivity.

PMID- 22412218
TI  - Taking away the diagnosis.

PMID- 22412219
TI  - The Shakespearean principle revisited.

PMID- 22412220
TI  - Texas Heart Institute Medal and the Ray C. Fish Award for Scientific Achievement
      in Cardiovascular Diseases.

PMID- 22412221
TI  - Peripartum cardiomyopathy: a review.
AB  - Peripartum cardiomyopathy is idiopathic heart failure occurring in the absence of
      any determinable heart disease during the last month of pregnancy or the first 5
      months postpartum. The incidence varies worldwide but is high in developing
      nations; the cause of the disease might be a combination of environmental and
      genetic factors. Diagnostic echocardiographic criteria include left ventricular
      ejection fraction <0.45 or M-mode fractional shortening <30% (or both) and end
      diastolic dimension >2.7 cm/m(2). Electrocardiography, magnetic resonance
      imaging, endomyocardial biopsy, and cardiac catheterization aid in the diagnosis
      and management of peripartum cardiomyopathy. Cardiac protein assays can also be
      useful, as suggested by reports of high levels of NT-proBNP, cardiac troponin,
      tumor necrosis factor-alpha, interleukin-6, interferon-gamma, and C-reactive
      protein in peripartum cardiomyopathy. The prevalence of mutations associated with
      familial dilated-cardiomyopathy genes in patients with peripartum cardiomyopathy
      suggests an overlap in the clinical spectrum of these 2 diseases.Treatment for
      peripartum cardiomyopathy includes conventional pharmacologic heart-failure
      therapies-principally diuretics, angiotensin-converting enzyme inhibitors,
      vasodilators, digoxin, beta-blockers, anticoagulants, and peripartum
      cardiomyopathy-targeted therapies. Therapeutic decisions are influenced by drug
      safety profiles during pregnancy and lactation. Mechanical support and
      transplantation might be necessary in severe cases. Targeted therapies (such as
      intravenous immunoglobulin, pentoxifylline, and bromocriptine) have shown promise
      in small trials but require further evaluation. Fortunately, despite a mortality
      rate of up to 10% and a high risk of relapse in subsequent pregnancies, many
      patients with peripartum cardiomyopathy recover within 3 to 6 months of disease
      onset.

PMID- 22412222
TI  - Does the expression of transforming growth factor beta-1: affect the outcome of
      the radiofrequency modified maze procedure in patients with rheumatic atrial
      fibrillation?
AB  - We investigated whether the expression of transforming growth factor beta-1 in
      the left atrial appendage affected the outcome of the radiofrequency modified
      maze procedure in patients with rheumatic valve disease and long-standing
      persistent atrial fibrillation.Messenger RNA and protein expression of
      transforming growth factor beta-1 and volume fractions of collagen types I and
      III were measured in 80 patients with rheumatic valve atrial fibrillation who
      underwent valve surgery with the radiofrequency modified maze procedure; the same
      was done in a control group of 20 patients with rheumatic valve disease and sinus
      rhythm who underwent valve surgery alone.At 6 months' follow-up, atrial
      fibrillation recurred in 24 of the 80 patients in the study group. The messenger
      RNA and protein expressions of transforming growth factor beta-1, collagen type I
      volume fraction, and left atrial dimension had increased gradually in the control
      group and in the study subgroups that maintained sinus rhythm or relapsed into
      atrial fibrillation (P <0.05). The messenger RNA and protein expressions of
      transforming growth factor beta-1 correlated positively with collagen type I
      volume fraction (r=0.723, P <0.001 and r=0.745, P <0.001, respectively) and left
      atrial dimension (r=0.762, P <0.001 and r=0.765, P <0.001, respectively). In the
      sinus rhythm-maintained subgroup, the patients who regained functional atrial
      contraction had lower messenger RNA and protein expression of transforming growth
      factor beta-1 than did the patients who failed to retain such function (P
      <0.05).We conclude that the expression of transforming growth factor beta-1 in
      the resected left atrial appendage affects the recurrence of atrial fibrillation
      and restoration of functional left atrial contraction after the radiofrequency
      modified maze procedure.

PMID- 22412223
TI  - On-label and off-label use of drug-eluting stents: comparison of short- and long
      term outcomes.
AB  - In this retrospective study, we compared the in-hospital and long-term outcomes
      of the on-label and off-label uses of drug-eluting stents.From April 2003 through
      June 2007, 1,538 patients underwent percutaneous coronary intervention with a
      drug-eluting stent (sirolimus or paclitaxel) at Tehran Heart Center. Off-label
      implantation of the drug-eluting stent was as implemented on the basis of
      specific clinical and procedural characteristics set forth in our text. There
      were 708 patients in the on-label group and 830 in the off-label group.Baseline
      characteristics were not significantly different between the groups. Histories of
      non-ST-segment-elevation myocardial infarction, percutaneous coronary
      intervention, and coronary artery bypass grafting were more prevalent in the off
      label group. Both groups had similar procedural and in-hospital complications.
      The follow-up rate at 1 year was 93.1% in the on-label group and 93.3% in the off
      label group. During that period, the occurrence of major adverse cardiac events
      was not significantly different between the groups. After 1 year between the
      respective on- and off-label uses of the sirolimus-eluting and paclitaxel-eluting
      stents, and after adjustment for diabetes mellitus, myocardial infarction,
      percutaneous coronary intervention, and coronary artery bypass grafting, there
      was no remarkable difference in the occurrence of major adverse cardiac events
      (hazard ratio, 0.688; 95% confidence interval, 0.365-1.295; P=0.2463) or target
      vessel revascularization (hazard ratio, 0.69; 95% confidence interval, 0.291
      1.636; P=0.3993).We found that off-label use of drug-eluting stents was safe
      after 1 year and that such use was not associated with increased in-hospital
      myocardial infarction or death.

PMID- 22412224
TI  - Carbohydrate antigen-125 and N-terminal pro-brain natriuretic peptide levels:
      compared in heart-failure prognostication.
AB  - Carbohydrate antigen-125 (CA-125) is emerging as a prognostic biomarker of risk
      in heart failure. In a prospective study, we compared the prognostic values of CA
      125 and amino-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with
      stable heart failure.We enrolled 102 consecutive chronic, stable, systolic-heart
      failure patients (68 men and 34 women; median age, 71 yr) from November 2008
      through February 2010. We measured baseline NT-proBNP and CA-125 levels and
      compared their prognostic values. The primary endpoint was all-cause death and
      other major adverse events, defined as hospitalization for decompensated heart
      failure or acute coronary syndrome.During a mean follow-up period of 14 +/- 2
      months, 12 patients died and 35 others sustained major adverse events. We found
      that CA-125 level significantly correlated with New York Heart Association
      functional class, pulmonary artery pressure, microalbuminuria, creatine kinase-MB
      fraction, and hemoglobin, albumin, and NT-proBNP levels. Upon receiver operating
      characteristic curve analysis, CA-125 and NT-proBNP had similar accuracy in
      predicting major adverse events and death: for major adverse events, area under
      the curve (AUC) was 0.699 for CA-125 (P=0.002) and 0.696 for NT-proBNP (P=0.002);
      for death, AUC was 0.784 for CA-125 (P=0.003) and 0.824 for NT-proBNP (P=0.001).
      Multivariate Cox regression analysis showed that CA-125 levels greater than 32
      U/mL and NT-proBNP levels greater than 5,300 pg/mL had independent prognostic
      value for major adverse events and death.We conclude that baseline CA-125 and NT
      proBNP levels are comparably reliable as heart-failure markers, and that CA-125
      can be used for prognosis prediction in heart failure.

PMID- 22412225
TI  - Accuracy of automated attenuation-based 3-dimensional segmentation: in the
      analysis of left ventricular function compared with magnetic resonance imaging.
AB  - We evaluated attenuation-based 3-dimensional segmentation for the analysis of
      left ventricular function, using as our standard of reference magnetic resonance
      imaging and dual-source computed tomography with traditional short-axis
      planimetry.Twenty patients with known or suspected coronary artery disease were
      examined prospectively. In all magnetic resonance and computed tomographic
      datasets, global functional values were determined by 2-dimensional planimetry.
      Computed tomographic scans were further evaluated by automated 3-dimensional
      segmentation, and the results were compared by Pearson correlation and Bland
      Altman analysis.Agreement between magnetic resonance imaging and dual-source
      computed tomographic 2-dimensional planimetry was good for all values (end
      diastolic volume, bias= -4.2, r=0.99; end-systolic volume, bias= -1.7, r=0.99,
      stroke-volume, bias= -2.4, r=0.98; ejection fraction, bias=0.26, r=0.94; and
      myocardial mass, bias= 2.5, r=0.90). By contrast, dual-source computed
      tomographic 3-dimensional segmentation overestimated end-diastolic volume (bias= 
      19.1, P <0.001), stroke-volume (bias= -16.9, P <0.001), and myocardial mass
      (bias= -34.4, P <0.001). Moreover, correlation with magnetic resonance imaging
      proved disappointing for ejection fraction (r=0.72). Results were similar in a
      direct comparison between dual-source computed tomographic 2-dimensional
      planimetry and 3-dimensional segmentation (end-diastolic volume, bias= -14.9,
      r=0.94; end-systolic volume, bias= -0.5, r=0.90; stroke volume, bias= -14.5,
      r=0.83; ejection fraction, bias= -2.8, r=0.74; and myocardial mass, bias= -36.8,
      r=0.79).Due to significant overestimation of volumes and poor correlation of
      ejection fraction with cine magnetic resonance imaging results, attenuation-based
      3-dimensional segmentation compares unfavorably with traditional planimetry.
      Hence this method should be used with caution, and its time benefits should be
      weighed against its imprecision of functional analysis.

PMID- 22412226
TI  - Prolactin and its 16-kDa N-terminal fragment: are higher in patients with
      precapillary pulmonary hypertension than in a healthy control group.
AB  - We sought to determine whether patients with precapillary pulmonary hypertension
      show elevated serum levels of prolactin (PRL) and its 16-kDa N-terminal fragment
      (16-kDa PRL) and whether there is any correlation to measures of prognosis.Twenty
      eight patients with idiopathic pulmonary artery hypertension, 15 with peripheral
      chronic thromboembolic pulmonary hypertension, and 4 with portopulmonary
      hypertension Child-Pugh class A were included. Our control subjects were 56 blood
      donors. Total prolactin was measured with an immunoluminometric assay. Antibodies
      against epitope C detected only the intact prolactin before it was split. The 16
      kDa PRL was calculated from the difference between total and intact
      prolactin.Prolactin was significantly (P=0.009) higher in the study group
      (median, 190 mU/L; interquartile range, 162 mU/L) than in the control group
      (median, 140 mU/L; interquartile range, 91 mU/L). The 16-kDa PRL was
      significantly elevated in the study group (P=0.046). Prolactin and 16-kDa PRL
      correlated inversely with the 6-minute-walk distance (P <0.01) and with peak
      oxygen uptake during exercise (P <0.005).Serum levels of prolactin and 16-kDa PRL
      were significantly higher in patients with precapillary pulmonary hypertension
      and were inversely correlated with 6-minute-walk distance and peak oxygen
      uptake.These results indicate that prolactin and 16-kDa PRL might play a role in
      the pathophysiology of precapillary pulmonary hypertension.

PMID- 22412227
TI  - Self-experimentation and its role in medical research.
AB  - Although experimentation involving human volunteers has attracted intense study,
      the matter of self-experimentation among medical researchers has received much
      less attention. Many questions have been answered only in part, or have been left
      unanswered. How common is this practice? Is it more common among certain
      nationalities? What have been the predominant medical fields in which self
      experimentation has occurred? How dangerous an act has this proved to be? What
      have been the trends over time? What is the future likely to bring?From the
      available literature, I identified and analyzed 465 documented instances of this
      practice, performed over the course of the past 2 centuries. Most instances
      occurred in the United States. The peak of self-experimentation occurred in the
      first half of the 20th century. Eight deaths were recorded. A number of the
      investigators enjoyed successful careers, including the receipt of Nobel Prizes.
      Although self-experimentation by physicians and other biological scientists
      appears to be in decline, the courage of those involved and the benefits to
      society cannot be denied.

PMID- 22412228
TI  - Congenital coronary artery ostial disease: a spectrum of anatomic variants with
      different pathophysiologies and prognoses.

PMID- 22412229
TI  - Ectopic and atretic ostium of left main coronary artery: from interleaflet
      triangle between left and noncoronary cusps.
AB  - Left main coronary artery atresia is an extremely rare coronary anomaly in which
      there is no left coronary ostium and the left main trunk ends blindly. Ectopic
      origin of the left coronary artery from the left ventricle is an even rarer
      condition. Herein, we describe the case of a 37-year-old woman whose left main
      coronary artery atresia was not corrected during previous surgical correction of
      patent ductus arteriosus and aortic insufficiency. Five years after that first
      operation, the patient developed severe angina and heart failure. She underwent
      coronary artery bypass grafting with greater saphenous vein directly to the left
      main coronary artery trunk, along with associated procedures. The operative
      findings revealed an ectopic and atretic ostium of the left main coronary artery
      from the interleaflet triangle between the left and noncoronary cusps, which we
      believe is a specific congenital coronary anomaly.

PMID- 22412231
TI  - Pulmonary endarterectomy: with use of moderate hypothermia and antegrade cerebral
      perfusion without circulatory arrest.
AB  - Pulmonary endarterectomy is the treatment of choice in suitable patients who have
      chronic thromboembolic pulmonary hypertension. The most common surgical technique
      involves the use of deep hypothermic circulatory arrest. Herein, we describe a
      modified aortic clamping technique with selective antegrade cerebral perfusion,
      performed with moderate hypothermia but without circulatory arrest. This
      technique avoids the adverse effects of deep hypothermic circulatory arrest and
      also establishes a bloodless surgical field. We achieved good surgical results
      and acceptable long-term outcomes in 3 patients with use of this technique, which
      we recommend as a feasible alternative to the standard operative practice.

PMID- 22412230
TI  - Rare variant of an anomalous left coronary artery: arising from the distal
      continuation of a single right coronary artery.
AB  - We report an interesting case of single right coronary artery arising from the
      right sinus of Valsalva and continuing distally as a rare anomalous left coronary
      artery. Over the 7-year course of our clinical follow-up, the right coronary
      artery manifested severe, progressive atherosclerotic disease in multiple sites,
      which lesions were successfully stented. We hypothesize that the disease process
      in the right coronary artery was accelerated by shear stress in association with
      that vessel's need to carry the entire burden of the coronary circulation.

PMID- 22412232
TI  - Prolonged QTc interval and torsades de pointes induced by citalopram.
AB  - Citalopram is a selective serotonin reuptake inhibitor with a favorable cardiac
      safety profile. Corrected QT interval (QTc) prolongation and cardiac arrhythmias
      have not been previously reported in association with citalopram use except in
      the presence of overdose, abnormal electrolyte values, or renal or liver failure.
      Herein, we report the case of a 40-year-old woman with mental depression who
      presented with a prolonged QTc interval and torsades de pointes after the
      initiation of citalopram at therapeutic doses. The QTc interval improved when
      citalopram therapy was discontinued. We recommend that clinicians investigate the
      family history for sudden deaths and perform baseline electrocardiography before
      prescribing citalopram. We also recommend routine electrocardiographic testing
      during citalopram therapy, and that patients with long QT syndrome avoid taking
      citalopram.

PMID- 22412233
TI  - Direct tissue evaluation via immunofluorescence: in the diagnosis of hereditary
      transthyretin cardiac amyloidosis.
AB  - Multiple precursor proteins have been shown to cause cardiac amyloidosis. The
      most common forms are due either to immunoglobulin light chains or to
      transthyretin proteins (either wild-type or mutant forms). Correct
      subclassification of the amyloid is paramount because treatment differs in
      accordance with the type of amyloidosis. Indirect diagnostic methods, including
      serologic analysis, can lead to misdiagnosis. Definitive diagnosis often requires
      analysis of amyloid in the tissue. We present a case of a woman who was diagnosed
      with hereditary transthyretin cardiac amyloidosis by means of immunofluorescence
      and genetic analysis. This case highlights the importance-in the diagnostic
      algorithm of cardiac amyloidosis-of direct evaluation of the tissue with
      immunofluorescence and of genetic testing.

PMID- 22412234
TI  - Metastatic carcinoid disease inducing coronary vasospasm.
AB  - Herein, we report a case of progressive coronary vasospasm in a 70-year-old man
      who had a long-standing history of metastatic gastrointestinal carcinoid tumor.
      Despite octreotide, nitrate, and calcium channel-blocker therapy, the patient's
      urinary 5-hydroxy-indole acetic acid level increased, coinciding with an
      increased frequency of flushing episodes with chest discomfort. In the cardiac
      catheterization laboratory, we captured an episode that was associated with
      diffuse right coronary artery spasm, ST-segment elevation, and intense symptoms.
      We attribute the patient's coronary vasospasm to his metastatic carcinoid
      disease.

PMID- 22412235
TI  - Metastatic colon cancer involving the right atrium.
AB  - Colorectal cancer rarely metastasizes to the heart. In the world medical
      literature, we identified only 7 cases of well-documented colorectal cancer
      metastasis to the right atrium. Herein, we describe the case of a 72-year-old man
      in whom metastatic mucinous adenocarcinoma of the colon involved the right atrium
      and caused superior vena cava syndrome. To our knowledge, this is the first case
      report of sudden cardiac death due to embolization of metastatic colon cancer
      from the right atrium. We also present the first comprehensive case series review
      of this rare entity.Given improvements in diagnostic and therapeutic methods that
      have increased the longevity of many cancer patients, the detection of cardiac
      metastases is likely to increase in frequency. Accordingly, we recommend that
      previously asymptomatic cancer patients with a history of colorectal cancer who
      develop cardiac symptoms undergo prompt investigation for possible cardiac
      metastasis.

PMID- 22412236
TI  - The multifaceted manifestations of cardiac tumors.

PMID- 22412237
TI  - Eptifibatide-induced thrombocytopenia: with thrombosis and disseminated
      intravascular coagulation immediately after left main coronary artery
      percutaneous coronary angioplasty.
AB  - Early clinical trials of eptifibatide did not show a significant association
      between eptifibatide and the development of thrombocytopenia, thrombosis, or
      disseminated intravascular coagulation. However, more recent literature has
      suggested a significant association between eptifibatide and the development of
      thrombocytopenia and thrombosis. Although the true incidence and the
      pathophysiology of these associations are unknown, the development of these
      events can be life-threatening. Herein, we describe the case of a patient who
      experienced acute onset of profound thrombocytopenia, developing thrombosis,
      pulmonary emboli, and disseminated intravascular coagulation. This paper adds to
      the few previous reports of cases that suggested an association between
      thrombocytopenia, thrombosis, and the administration of eptifibatide. To the best
      of our knowledge, this is the first case report in the medical literature that
      associates the new onset of thrombocytopenia, thrombosis, and disseminated
      intravascular coagulation with the administration of eptifibatide. We also
      provide a subject review.

PMID- 22412238
TI  - Spontaneous coronary artery dissection during cabergoline therapy.
AB  - Although spontaneous coronary artery dissection is a rare cause of acute coronary
      syndrome, it should be considered during the evaluation of patients who have
      chest pain. Coronary vasospasm can lead to spontaneous dissection. The dopamine
      agonist cabergoline is known to cause digital vasospasm. Herein, we report a case
      of spontaneous right coronary artery dissection in a 43-year-old woman who was
      taking cabergoline as therapy for prolactinoma. To our knowledge, this is the
      first report of an apparent relationship between cabergoline therapy and
      spontaneous coronary artery dissection. The possible association of cabergoline
      with coronary artery spasm and dissection should be considered in patients who
      present with chest pain while taking this medication.

PMID- 22412239
TI  - Spontaneous right coronary artery dissection: causing myocardial infarction in a
      36-year-old woman.
AB  - Spontaneous coronary artery dissection is a rather rare cause of myocardial
      infarction, chest pain, and sudden death. Since the condition was first described
      in 1931, fewer than 200 cases have been reported in the medical literature. There
      are currently no known direct causes of this condition, although some
      correlations have been noted. Many patients are women in the peripartum period or
      of childbearing age, with few or no risk factors for coronary artery disease.
      Other associations include contraceptive use and connective-tissue disorders,
      Ehlers-Danlos and Marfan syndromes, and polyarteritis nodosa. Most of the
      reported dissections have occurred in the left anterior descending coronary
      artery. Herein, we report the case of a 36-year-old woman who presented at our
      institution with an acute ST-elevation myocardial infarction secondary to a
      spontaneous dissection of the right coronary artery. Thrombectomy and stenting
      resolved the occlusion of the artery, and the patient was discharged from the
      hospital on medical therapy. We discuss the pathophysiology, presentation, and
      treatment of this rare and often fatal condition.

PMID- 22412240
TI  - Tirofiban-induced diffuse alveolar hemorrhage: after primary angioplasty.
AB  - Platelets play an important role in the development of acute coronary syndromes.
      Evidence indicates that platelet-inhibiting drugs, such as glycoprotein IIb/IIIa
      inhibitors, can be beneficial when they are administered at the time of primary
      percutaneous coronary intervention for acute ST-segment-elevation myocardial
      infarction. However, an associated increase in the risk of bleeding is well
      documented. Diffuse alveolar hemorrhage is a rare but life-threatening and
      underdiagnosed complication of therapy with glycoprotein IIb/IIIa inhibitors.
      Diffuse alveolar hemorrhage can easily be mistaken for acute pulmonary edema, a
      condition commonly seen in patients with acute coronary syndrome. Physicians need
      to be aware of this diagnostic dilemma, because early treatment increases the
      chance that the patients will survive.Herein, we report the fatal outcome of
      diffuse alveolar hemorrhage in a 73-year-old man who presented with acute ST
      segment-elevation myocardial infarction and was treated with tirofiban in
      conjunction with primary percutaneous coronary intervention. In addition, we
      review the medical literature pertaining to the sequelae of glycoprotein IIb/IIIa
      inhibitor therapy in the presence of diffuse alveolar hemorrhage.

PMID- 22412241
TI  - Left circumflex coronary artery occlusion after mitral valve annuloplasty: "a
      stitch in time".
AB  - The left circumflex coronary artery is susceptible to injury during mitral valve
      surgery because of its proximity to the mitral valve annulus. We report the case
      of a 73-year-old woman who had undergone mitral valve repair and experienced a
      perioperative myocardial infarction due to occlusion of the left circumflex
      coronary artery. After percutaneous coronary intervention, a fistulous
      communication had developed between the stented portion of the left circumflex
      coronary artery and the left atrium, which, to our knowledge, is the first report
      of such a complication. The patient underwent successful mitral valve
      replacement. Although injuries to the left circumflex coronary artery are rare
      during mitral valve surgery, we believe that increasing awareness of the risk
      will help to prevent potentially fatal complications. We also recommend that
      surgeons gather as much detail as possible about the patient's anatomy before
      operation, use careful and meticulous surgical techniques, and use
      transesophageal echocardiography to look for wall-motion abnormalities before
      closing the incision.

PMID- 22412242
TI  - Inoue balloon mitral valvotomy in a 4-year-old boy: to treat fulminant rheumatic
      mitral stenosis.
AB  - Mitral stenosis in children often has a fulminant and rapid course. Percutaneous
      transvenous mitral commissurotomy is accepted as the treatment of choice for
      mitral stenosis not only in adults, but also in younger patients who have pliable
      valves. Balloon mitral valvotomy has yielded good immediate and long-term
      results. Herein, we report successful Inoue balloon mitral valvotomy in a 4-year
      old boy who had severe, symptomatic rheumatic mitral stenosis. To our knowledge,
      our patient is the youngest to have undergone this procedure. In addition to the
      case description, we discuss the features of juvenile rheumatic mitral stenosis
      and several technical aspects of performing the Inoue balloon mitral valvotomy
      procedure in children.

PMID- 22412243
TI  - Double guiding catheters for complex percutaneous coronary intervention.
AB  - A large-lumen guiding catheter is often used for complex percutaneous coronary
      intervention-particularly when a final kissing-balloon or 2-stent technique is
      required. However, catheter insertion is sometimes restricted by diseased
      vascular access sites or a tortuous vascular route.We report 2 cases in which a
      unique double guiding catheter technique was used to create a lumen of sufficient
      size for complex percutaneous coronary intervention. In each patient, two 6F
      guiding catheters were used concurrently to engage the ostium of 1 target vessel.
      In 1 patient, these catheters were used for the delivery of 2 balloons to
      complete kissing-balloon dilation after single-stent placement. In the other
      patient, the catheters were used to deliver 2 stents sequentially to their
      respective target lesions. The stents were then deployed simultaneously as
      kissing stents, followed by high-pressure kissing-balloon postdilation.

PMID- 22412244
TI  - Epicardial mass causing cardiac compression: an unusual involvement in
      lymphomatoid granulomatosis.
AB  - Lymphomatoid granulomatosis is a rare, diffuse, large B-cell lymphoma that is
      positive for Epstein-Barr virus. A multiorgan process, it manifests itself
      chiefly in the lungs but can also affect the skin, nervous system, and kidneys.
      Cardiac involvement and pericardial effusion are very unusual. We report the case
      of a 62-year-old man with lymphomatoid granulomatosis involving the heart and
      lungs. Diagnosis was confirmed with wedge biopsy at pericardiotomy, and the
      patient was treated with cyclophosphamide, prednisolone, and vincristine.
      Although the patient was still symptomatic at 6-month follow-up, he was in
      partial remission with improved functional capacity.

PMID- 22412245
TI  - Two-dimensional speckle strain imaging: in the management of paraganglioma, acute
      junctional tachycardia, and myocardial dysfunction in a child.
AB  - Two-dimensional speckle-tracking strain imaging (speckle strain imaging) is
      useful for evaluating left ventricular myocardial function in patients with
      ischemic heart disease and cardiomyopathy, including hypertrophic and dilated
      phenotypes. The usefulness of speckle strain imaging in patients with
      pheochromocytoma who are undergoing adrenal surgery has been described, but we
      found no reports of the use of this method to evaluate ventricular dysfunction
      longitudinally in children. Herein, we describe the case of a 10-year-old girl
      with a paraganglioma, acute junctional tachycardia, and myocardial dysfunction.
      After control of the tachycardia and partial resection of the tumor, speckle
      strain imaging enabled clinical management that led to substantial improvement in
      the patient's initially diffuse myocardial dysfunction. Because conventional
      echocardiographic methods alone may be inadequate to guide the management of
      pediatric patients with partially resected neuroendocrine tumors, we recommend
      speckle strain imaging as an additional noninvasive option for treatment guidance
      and monitoring of cardiac tissue response.

PMID- 22412246
TI  - Impact of a large hemodialysis arteriovenous fistula: on myocardial protection
      during cardiopulmonary bypass.
AB  - Arteriovenous fistulae have a substantial impact on systemic hemodynamics, but
      their effect on cardiopulmonary bypass is not well understood. The left-to-right
      shunting of blood through an arteriovenous fistula can create flow problems
      during cardiopulmonary bypass. We present the case of a 59-year-old man with end
      stage renal disease who underwent coronary artery bypass grafting. During
      surgery, a large brachiocephalic arteriovenous fistula provided excessive venous
      return to the heart, compromising the myocardial protection offered by
      cardiopulmonary bypass. We modified the venous cannulation from a 2-stage single
      cannula to a bicaval cannula and were then able to achieve cardioplegic arrest
      and myocardial protection with no further problems.

PMID- 22412247
TI  - Left anterior descending coronary artery stenosis: in a patient with takotsubo
      cardiomyopathy.
AB  - Takotsubo cardiomyopathy is characterized by chest pain, electrocardiographic
      abnormalities such as ST-segment elevation or depression, and elevated cardiac
      enzyme levels. Left ventriculography reveals transient akinesis of the involved
      segment of the myocardial wall (usually the left ventricular apex) and
      compensatory hyperkinesis of the noninvolved myocardium, which appears as apical
      ballooning during systole. Existing criteria for the diagnosis of takotsubo
      cardiomyopathy include the absence of obstructive coronary artery disease.
      Indeed, previous investigators have found incidental stenosis in only a minority
      of patients.Herein, we present the unusual case of an 84-year-old woman who
      sustained 4 episodes of takotsubo cardiomyopathy in 18 years. At the time of the
      initial episode, coronary angiography revealed no substantial stenosis.
      Concomitant with the 2nd episode, stenosis in the 1st obtuse marginal branch was
      treated with stenting. No new lesions were apparent after the patient's 3rd
      presentation, and the previously placed stent was patent. During the 4th
      (current) presentation, we detected and percutaneously treated severe stenoses in
      the patient's left anterior descending coronary artery and 2nd obtuse marginal
      branch.Although this report is of a single patient only, it definitively
      illustrates that severe coronary artery disease can occur in patients who have
      takotsubo cardiomyopathy. We recommend the thorough evaluation of possible
      coronary artery disease in high-risk patients, even upon the strong clinical
      suspicion of takotsubo cardiomyopathy.

PMID- 22412248
TI  - Gunshot wounds: causing myocardial infarction, delayed ventricular septal defect,
      and congestive heart failure.
AB  - Penetrating chest trauma can cause a wide variety of cardiac injuries, including
      myocardial contusion, damage to the interventricular septum, laceration of the
      coronary arteries, and free-wall rupture. Herein, we describe the case of a 21
      year-old man who presented with congestive heart failure, which was secondary to
      an old myocardial infarction and complicated by the delayed formation of a
      ventricular septal defect. All of these conditions were attributable to multiple
      gunshot wounds that the patient had sustained 6 months earlier. Left ventricular
      angiography showed an apical aneurysm; a large, muscular, ventricular septal
      defect; and 19 gunshot pellets in the chest wall. Three months after
      aneurysmectomy and surgical closure of the septal defect, the patient had
      recovered fully and was asymptomatic.This case reaffirms the fact that
      substantial cardiac injuries can appear months after chest trauma. The
      possibility of traumatic ventricular septal defect should be considered in all
      multiple-trauma patients who develop a new heart murmur, even when overt chest
      wall injury is absent.

PMID- 22412249
TI  - Isolated right ventricular infarction after modified Cabrol operation.
AB  - We report the case of a 27-year-old woman with a rare presentation of right
      ventricular failure secondary to isolated right ventricular myocardial
      infarction, 3 weeks after an uncommon surgical procedure, the modified Cabrol
      operation. Her medical history also included a Ross procedure at the age of 12
      years. On the basis of her subacute presentation and a consultation with cardiac
      surgeons, we decided on medical management. Follow-up echocardiography at 6
      months revealed that the right ventricular systolic function remained severely
      impaired, but the patient was asymptomatic with excellent functional capacity.We
      review the surgical techniques of aortic graft replacement and their respective
      complications. We also discuss the impact of conservative and reperfusion
      strategies on prognosis and long-term outcomes in the setting of right
      ventricular infarction.

PMID- 22412250
TI  - Familial hypertrophic cardiomyopathy with atypical location: diagnosis by means
      of echocardiography and cardiovascular magnetic resonance.

PMID- 22412251
TI  - Primary percutaneous intervention: for acute myocardial infarction in a patient
      with dextrocardia and situs inversus.

PMID- 22412252
TI  - Femoral artery dissection and occlusion: after repeat percutaneous closure.

PMID- 22412253
TI  - Percutaneous treatment of iatrogenic left main ostial stenosis: after a Bentall
      operation.

PMID- 22412254
TI  - Aorto-atrial fistula in the absence of infective endocarditis: diagnosis by 2-
      and 3-dimensional transesophageal echocardiography.

PMID- 22412255
TI  - Rupture of abdominal aortic aneurysm: with fistula between the aorta and the
      confluence of the left renal vein into the vena cava.

PMID- 22412256
TI  - Large, isolated aortic valve aneurysm: detected on real-time 3-dimensional
      echocardiography.

PMID- 22412257
TI  - Right atrial angiosarcoma: rupture and tamponade.

PMID- 22412258
TI  - Total extrusion of a normally functioning pacemaker.

PMID- 22412261
TI  - Contrast-induced coronary no-flow phenomenon.

PMID- 22412259
TI  - Takotsubo cardiomyopathy after midodrine therapy.

PMID- 22412262
TI  - Change of guard.

PMID- 22412263
TI  - Chronic cerebrospinal venous insufficiency in Multiple Sclerosis: A note for
      caution.

PMID- 22412264
TI  - Paraneoplastic neurologic syndrome: A practical approach.
AB  - Paraneoplastic neurological syndromes (PNS) are rare disorders associated with
      cancer, not caused by direct invasion, metastasis or consequences of treatment.
      They are usually autoimmune in nature. Often, PNS precedes the manifestations of
      cancer. Onconeural antibodies are important in the diagnosis and management of
      these disorders. These antibodies are specific for the malignancy rather than for
      a particular neurological syndrome. Often, there are different antibodies
      associated with the same syndrome. Multiple antibodies are also known to coexist
      in a given patient with malignancy. While investigating a patient for suspected
      PNS, the entire gamut of onconeural antibodies should be investigated so as not
      to miss the diagnosis. In 30-40% of the cases, PNS can occur without antibodies.
      Investigations for identifying the underlying cancer can be directed by the
      antibody panel. If conventional screening for cancer is negative, a positron
      emission scanning/computed tomography scan can be useful. Patients need follow-up
      surveillance for cancer if not detected in the first instance. Cancer detection
      and treatment, immunotherapy and supportive care are important components of
      treatment of PNS. Immunotherapy is very effective in PNS associated with cell
      membrane-associated antibodies like voltage-gated potassium channel complex, NMDA
      receptor antibodies and voltage-gated calcium channel antibodies. Immunotherapy
      includes steroids, IVIgG, plasmaphereis, cytotoxic medications and rituximab.
      Supportive therapy includes symptomatic treatment with antiepileptic and
      analgesic medications, physiotherapy, speech therapy and occupational therapy.
      PNS can mimic any neurologic syndrome. A high index of clinical suspicion is
      important for early diagnosis and prompt management and better outcome.

PMID- 22412265
TI  - Mirror movements.

PMID- 22412266
TI  - Forty-year-old diabetic lady with tightness in lower limbs.

PMID- 22412267
TI  - Low cholesterol as a risk factor for primary intracerebral hemorrhage: A case
      control study.
AB  - INTRODUCTION: An inverse association between serum cholesterol and the risk of
      hemorrhagic stroke has been noted in epidemiological studies. We performed a case
      control study to assess the relationship between primary intracerebral hemorrhage
      (ICH) and low serum cholesterol. MATERIALS AND METHODS: Prospectively recruited
      fully evaluated patients with ICH were compared with a control group based in a
      primary care practice, i.e. age- and sex-matched individuals attending the
      routine preventive health check-up. Low cholesterol was defined by the sex
      specific lowest quintile of the population. RESULTS: The proportion of ICH
      patients with low cholesterol was significantly higher than the controls (68% vs.
      43%). Mean total cholesterol was also signficantly low in ICH patients compared
      with controls (177 mg/dL vs. 200 mg/dl; P-value = 0.0006). Low-density
      lipoprotein cholesterol (LDL-c) and triglycerides were also significantly low in
      ICH patients compared with controls. Mean LDL-C in the ICH patient group was 114
      mg/dL, whereas it was 128.5 mg/dL in the control group (P-value = 0.016). There
      was no significant difference in the high-density lipoprotein (HDL) levels in
      both groups. In a subgroup analysis, both men and women in the ICH group had a
      significantly low mean cholesterol compared with the control group. Although
      lower mean cholesterol was seen in both young and older individuals in the ICH
      group than in controls, the difference was significant only in the older group
      (age >45 years). In multivariate analysis, presence of low cholesterol remained a
      significant predictor of hemorrhage. The odds ratio of low cholesterol in the
      hemorrhage cases was 2.75 (95% CI = 1.44-5.49) unadjusted and 2.15 (1.13-4.70)
      adjusted for age and hypertension. CONCLUSIONS: This study confirms an increased
      risk of primary ICH associated with low cholesterol both in men and women,
      especially in older individuals.

PMID- 22412268
TI  - Prevalence of mental retardation among children in RS Pura town of Jammu and
      Kashmir.
AB  - OBJECTIVE: To determine the Prevalence of mental retardation in children 3 to 10
      years of age. MATERIALS AND METHODS: The study was conducted in the framework of
      a population based, single centre, cross-sectional study at R.S.Pura town, 22 kms
      south- west of Jammu city. RESULTS: A total of 61 (0.79 percent) of the 7,707
      children surveyed had positive screening results on the Ten Questions instrument.
      56 (0.72percent) children were diagnosed as suffering from mental retardation.
      Serious mental retardation was diagnosed in 48 children and mild mental
      retardation was diagnosed in 8 children. The combined prevalence estimates of
      mild and serious mental retardation were 7.2/1000. No notable sex differences
      were observed for either serious or mild retardation. INTERPRETATION: The
      prevalence rates of mental retardation among children less than 19 years of age
      in R. S. town compares favorably with studies from developed world.

PMID- 22412269
TI  - Temporal arteritis: A case series from south India and an update of the Indian
      scenario.
AB  - OBJECTIVE: To study the clinical, pathological and prognostic profile of patients
      with temporal arteritis in India. MATERIALS AND METHODS: The study was conducted
      in a tertiary care center from south India from 2005 to 2010 in the departments
      of neurology and medicine. The details of all patients that satisfied the ACR
      1990 criteria for diagnosis of temporal arteritis were reviewed. The clinical
      presentation, laboratory parameters and biopsy findings of the patients were
      analyzed and compared with other studies from India done over the last decade.
      RESULTS: A total of 15 patients were diagnosed with temporal arteritis. The
      male:female ratio was 1.5:1. The mean age of onset was 67.58 years. Mean time for
      detection after onset of symptoms was 2.56 months. Typical manifestations
      included headache (100%), temporal artery tenderness (100%), jaw claudication
      (20%), polymyalgia rheumatica (53%) and visual manifestations (20%). The
      erythrocyte sedimentation rate was elevated in all patients. Biopsy was done in
      13 patients, with 11 of them being positive. All patients responded to steroids
      well, with most patients being symptom-free within the first 48 h of treatment.
      CONCLUSIONS: Temporal arteritis seems to be underdiagnosed in India, with all
      patients previously misdiagnosed, and with a mean time from symptom onset to
      diagnosis of 2.5 months. The clinical presentation of temporal arteritis in India
      appears to be similar to that of the West, with no gender preference and a
      slightly younger age group.

PMID- 22412270
TI  - Glutaric aciduria type I: A treatable neurometabolic disorder.
AB  - BACKGROUND AND OBJECTIVES: Glutaric aciduria Type-I (GA-I) has characteristic
      clinical and neuroimaging features, which clinches the diagnosis in a majority of
      patients. However, there have been few case reports on GA-I from India. This
      study was undertaken to study the clinical presentations, metabolic profile,
      neuroimaging findings and outcome of patients with GA-I. STUDY DESIGN: The
      present study was a retrospective study. MATERIALS AND METHODS: Retrospective
      review of charts of patients with a diagnosis of GA-I was carried out from March
      2008 to April 2010. The clinical, laboratory and neuroimaging findings were
      extracted in a predesigned proforma and the data was analyzed. RESULTS: Eleven
      cases were found to have GA-1. Clinical presentation was quite varied. Follow-up
      of patients revealed that one patient with macrocephaly as the only clinical
      finding was developmentally normal. One patient with encephalitis-like illness
      steadily improved and started walking at 2 years. Two patients were bed ridden
      and had severe dystonia. One patient died during follow-up. The remaining six
      patients had dystonia and other abnormal movements, but had attained sitting
      without support and were not ambulatory. CONCLUSION: GA-I is not an uncommon
      disorder and diagnosis can be made easily based on clinical, laboratory
      investigations and neuroimaging findings. It is one of the treatable metabolic
      disorders and, if managed appropriately, favorable prognosis can be given.

PMID- 22412271
TI  - Use of thrombolytic therapy in cerebral venous sinus thrombosis with ulcerative
      colitis.
AB  - Cerebral venous thrombosis developing concurrently with active ulcerative colitis
      poses a therapeutic dilemma. We report the case of a 31-year-old woman who
      developed dural venous sinus thrombosis during the course of active ulcerative
      colitis in whom we accomplished clot lysis using intrasinus urokinase. The
      success of the procedure was assessed by improvement in the patient's
      neurological condition and resolution of imaging features without any bleeding
      complications. We also reviewed literature on various modalities of treatment of
      sinus venous thrombosis in patients with ulcerative colitis and outcome.

PMID- 22412272
TI  - Restless leg syndrome, periodic limb movements, febrile seizures and Attention
      deficit hyperactivity disorder in an Indian family.
AB  - Restless leg syndrome (RLS) is a common neurological disorder which can affect
      individuals of all age groups and incidence increasing with age. It can cause
      severe sleep disruption and negatively impact quality of life of an individual.
      Its diagnosis is clinical, based on essential criteria of International RLS Study
      Group. It can be idiopathic or associated with various medical and other
      neurological disorders. Idiopathic RLS can be sporadic or may have a familial
      inheritance, with several genetic loci been reported till date. RLS has a strong
      association with periodic limb movements, both sleep and awake. Very few studies
      of familial RLS/Periodic limb movements in sleep and their associations have been
      reported. We report an Indian family with autosomal dominant RLS/PLMS, with RLS
      and PLMS as well as psychiatric disorders, febrile seizures and Attention Deficit
      Hyperactivity Disorder in different family members, over three generations.

PMID- 22412273
TI  - Familial Guillain-Barre syndrome: First Indian report.
AB  - Guillain-Barre syndrome (GBS) is the commonest acute immune-mediated peripheral
      neuropathy. Specific human leukocyte antigen types have been found in patients
      with axonal and demyelinating subtypes of GBS suggesting genetic susceptibility
      in the generation of GBS. However, familial occurrence of GBS is rare and 42
      patients from 20 families have been reported. Majority of them are from European
      countries and two families have been documented from Asian countries, while none
      have been reported from India. Electrophysiological characterization in familial
      GBS has been limited. We report the clinical and detailed electrophysiological
      findings in two affected brothers with familial GBS from India who had GBS five
      years apart. Both of them had mixed axonal and demyelinating features in nerve
      conductions and had complete clinical recovery. Our report documents the first
      Indian familial occurrence of GBS. Detailed genetic and epidemiological studies
      are required to find the true prevalence of familial GBS.

PMID- 22412274
TI  - Rare association of central pontine myelinolysis with infantile tremor syndrome.
AB  - Central pontine myelinolysis (CPM) is an acute demyelination within the central
      basis pontis. Though exact mechanism is not known it is seen commonly with rapid
      correction of hyponatremia and also with pontine ischemia or infarction,
      demyelinating diseases, pontine neoplasm and different metabolic diseases. We
      report a rare association of CPM in a patient of Infantile Tremor Syndrom (ITS).
      ITS is a syndrome of tremor, mental and physical retardation, pigmentary changes
      of hair and skin and anemia in malnourished children. Though first reported in
      Indian subcontinent many identical cases were reported from around the world. Our
      case is a 15 month old child with generalized tremor, mild hepatosplenomegaly
      with features of grade II malnutrition including skin and hair changes. All the
      signs and symtoms of tremor improved after treatment with the World Health
      Organization (WHO) protocol for protein energy malnutrition (PEM) and
      administration of propranolol without any side effects.

PMID- 22412275
TI  - Seizure, spinal schwannoma, peripheral neuropathy and pulmonary stenosis - A rare
      combination in a patient of Neurofibromatosis 1.
AB  - Neurofibromatosis 1 (NF1) is the most common neurocutaneous syndrome. It is
      estimated to occur in approximately 1 out of every 3300 infants. The
      manifestations of this condition are diverse and can arise from almost any system
      in the body. The neurofibroma is the hallmark lesion of NF1 that develops from
      peripheral nerves. Here, we are reporting an 18-year-old girl with NF1. Clinical
      diagnosis was made according to the diagnostic criteria established by the
      National Institutes of Health Consensus Development Conference in 1987. She
      presented with quadriparesis due to dumbbell-shaped spinal schwannoma in the
      cervical region. She had history of recurrent seizures in the past, with poor
      scholastic performance. There were clinical and electrophysiological features of
      peripheral neuropathy and clinical and echocardiographical features of pulmonary
      stenosis. These are uncommon features of NF 1. The presence of all these features
      in a single patient makes it a unique case.

PMID- 22412276
TI  - Mycobacterium avium-intracellulare brain abscess in HIV-positive patient.
AB  - Mycobacterial opportunistic infections are a major cause of morbidity and
      mortality among patients living with HIV (PLHIV) worldwide. Nontuberculous
      mycobacterial (NTM) infection is one of the leading causes of opportunistic
      infection in patients with advanced acquired immunodeficiency syndrome i.e., with
      CD4 count less than 50/cu.mm. Mycobacterium avium complex (MAC) is among the most
      common opportunistic bacterial infections in those patients with advanced
      immunodeficiency apart from cryptococcal meningitis, progressive multifocal
      leukoencephalopathy, etc. Common presentations of mycobacterium avium complex are
      fever, lymphadenitis and respiratory disease. Immune reconstitution disease is
      also known to manifest with MAC infections in PLHIV on highly active
      antiretroviral therapy. Very few cases of central nervous system involvement due
      to NTM infection have been described. We are reporting a case of advanced
      acquired immunodeficiency who presented with brain abscess due to Mycobacterium
      avium intracellulare.

PMID- 22412277
TI  - Hypertrophic pachymeningitis in a patient with Takayasu arteritis: One more
      association?
AB  - Hypertrophic pachymeningitis (HP) is a rare chronic inflammatory disease of the
      dura mater, described in association with various infections, systemic
      vasculitides such as Wegener's granulomatosis and giant cell arteritis. However,
      HP in association with Takayasu arteritis (TA) has not been described. We report
      a young woman who presented with headache, seizures, and right third and fourth
      cranial neuropathy. Magnetic resonance imaging of the brain showed HP in
      bifrontal and right temporal region extending to cavernous sinus. She was also
      found to have systemic hypertension, stenosis of left subclavian, and left renal
      artery with narrowing of abdominal aorta, satisfying the diagnostic criteria for
      TA. A detailed evaluation for secondary causes of HP failed to reveal an
      alternative etiology. This report describes an unusual association of HP in a
      patient with TA, also emphasizing that seizures and cranial neuropathy may
      further expand the spectrum of neurological manifestations in patients with TA.

PMID- 22412278
TI  - Cerebral infarction following intracranial hemorrhage in pediatric Moyamoya
      disease - A case report and brief review of literature.
AB  - Moyamoya disease is a clinical entity characterized by progressive
      cerebrovascular occlusion with spontaneous development of a collateral vascular
      network called Moyamoya vessels. This disease mainly manifests as cerebral
      ischemia. Intracranial bleeding is another major presentation of patients with
      Moyamoya disease. We report here a 12-year-old male child who presented with
      severe headache, vomiting and meningismus. Initial neuroimaging study with
      noncontrast computed tomography scan revealed fresh intraventricular hemorrhage
      in right-sided lateral ventricle. Magnetic resonance imaging with angiography of
      brain was done 5 days later when the child developed right-sided hemiparesis, and
      the diagnosis of Moyamoya disease was confirmed along with lacunar infarction of
      right posterior peri and paraventricular area and in the left paraventricular
      area and centrum semiovale. Simultaneous presence of cerebral infarction along
      with intraventricular hemorrhage in adult with bleeding-type Moyamoya disease is
      reported in literature, but it is a rare entity in a child.

PMID- 22412279
TI  - The withering shine of white coat.

PMID- 22412280
TI  - Neurologists' role in antimicrobial resistance.

PMID- 22412281
TI  - Cysticercosis and ptosis.

PMID- 22412282
TI  - Occupational health and safety in chemical industries in transitional economies.

PMID- 22412283
TI  - Oxidative stress effects of thinner inhalation.
AB  - Thinners are chemical mixtures used as industrial solvents. Humans can come into
      contact with thinner by occupational exposure or by intentional inhalation abuse.
      Thinner sniffing causes damage to the brain, kidney, liver, lung, and
      reproductive system. We discuss some proposed mechanism by which thinner induces
      damage. Recently, the induction of oxidative stress has been suggested as a
      possible mechanism of damage. This paper reviews the current evidence for
      oxidative stress effects induced by thinner inhalation. Early ideas about the
      effects of thinner on lipids are discussed in one section. We discuss several
      studies that have shown the oxidative effects of thinner inhalation on: lipid
      peroxidation, levels of antioxidant enzymes, glutathione depletion, and oxidation
      of proteins and DNA. We have also included studies about oxidative stress effects
      induced by toluene, the principal component (60-70%) of thinner. Finally, work
      describing the effects of oxidative stress induced by thinner inhalation on
      different organs is discussed.

PMID- 22412284
TI  - Health and environmental sanitation in India: Issues for prioritizing control
      strategies.
AB  - Environmental sanitation is a major public health issue in India. Recent
      interventional studies on environmental sanitation in India highlighted the
      importance of prioritizing control strategies. Research related to the
      appropriate cost-effective intervention strategies and their implementation in
      Indian context is a big challenge. This paper discusses various intervention
      strategies related to environmental sanitation in India and emphasizes to
      prioritize it according to the need of country.

PMID- 22412285
TI  - Disaster management as part of curriculum for undergraduate and postgraduate
      courses: The Symbiosis model.
AB  - From times immemorial disasters in some form or the other have been regularly
      visiting humankind and humans have been trying to manage these upheavals. Noah's
      arch is the first such endeavor. The United Nations declared 1990-1999 as
      International Decade for Disaster Reduction. The Indian Government passed the
      Disaster Management Act 2005. As a consequence of the Act, the National Disaster
      Management Authority was setup. All states were given the guide lines for
      disaster risk reduction. The objective of this article is to get a clearer
      picture of what various states, educational authorities and international bodies
      have done and what Symbiosis International University (SIU) has done so far.
      Inputs from various States of the Indian Union and neighboring countries were
      studied. The moot question that figured all the time was "Is there a conscious
      effort to include Disaster Management in the curricula of various courses at the
      college and university level" and what are the achievements. It was seen that the
      Central Board for Secondary Education with support from the Ministry of Home
      Affairs, Ministry of Human Resource Development and United Nations Development
      Project have incorporated DM, as part of its frontline curriculum. Most of the
      Universities in the disaster prone states have enunciated policies for including
      DM in the curriculum, but palpable results are still awaited. In the SIU, DM has
      been incorporated in the curriculum and is mandatory for all undergraduate and
      postgraduate courses.

PMID- 22412286
TI  - Public health impact of plastics: An overview.
AB  - Plastic, one of the most preferred materials in today's industrial world is
      posing serious threat to environment and consumer's health in many direct and
      indirect ways. Exposure to harmful chemicals during manufacturing, leaching in
      the stored food items while using plastic packages or chewing of plastic teethers
      and toys by children are linked with severe adverse health outcomes such as
      cancers, birth defects, impaired immunity, endocrine disruption, developmental
      and reproductive effects etc. Promotion of plastics substitutes and safe disposal
      of plastic waste requires urgent and definitive action to take care of this
      potential health hazard in future.

PMID- 22412287
TI  - Incidence of silicosis in flourmill workers.
AB  - BACKGROUND: Silicosis is an ancient occupational illness reported in silica mill
      workers, agate stone workers, slate pen workers and mining industry. However its
      association in flour mill workers has not been established. AIMS: To study the
      incidence of silicosis and respiratory morbidity in flour mill workers. SETTINGS
      AND DESIGN: A prospective study of 56 flour mill workers working with open silica
      grinding stones was undertaken. MATERIALS AND METHODS: 56 flour mill workers who
      volunteered following information regarding the study purpose were recruited from
      the community. Detailed clinical and occupational history, lung functions, chest
      x-ray, and high resolution computed tomography (HRCT) were done. Diagnosis was
      made on the basis of radiological findings. STATISTICAL ANALYSIS: Data analysis
      was done with the help of the statistical package for social sciences software.
      The Chi-square test was used for determining the relationship between qualitative
      data and descriptive statistics was used where required. RESULTS: 93% had
      respiratory symptoms that included cough (66.1%), dyspnea (75%), chest pain
      (17.1%), and rhinorrhea (46.4%). Radiological abnormalities were noted in chest X
      ray (60.7%) and HRCT (81.48%). A significant correlation was seen between
      duration of exposure and HRCT abnormalities. Lung functions revealed obstruction
      in 28.5% subjects, restriction in 19%, mixed ventilatory defects in 21.4%, while
      18.9% had a reduced diffusion capacity. CONCLUSION: Incidence of silicosis in our
      study on flour mill workers working with silica containing grinding stones was
      30.4%. They had high respiratory morbidity (93%) cough and dyspnea being
      predominant symptoms. Duration of exposure correlates with radiological findings
      and increased incidence of silicosis.

PMID- 22412288
TI  - Assessment of awareness regarding climate change in an urban community.
AB  - BACKGROUND: Climate change has emerged as one of the most devastating
      environmental threats. It is essential to assess the awareness regarding climate
      change in the general population for framing the mitigation activities. AIM: To
      assess the awareness regarding climate change in an urban community. SETTINGS AND
      DESIGN: Urban field practice area of a medical college in the Pune city.
      Observational study. MATERIALS AND METHODS: The cross-sectional survey was
      conducted in the urban adult population who had given the written consent. A pre
      tested questionnaire was used for a face to face interview. Responses were
      evaluated. STATISTICAL ANALYSIS USED: Proportions, percentage. RESULTS: Total 733
      respondents above 18 years of age were included in the present survey. 672
      (91.68%) respondents commented that global climate is changing. 547 (81.40%)
      respondents opined that human activities are contributing to climate change. 576
      (85.71%) respondents commented that climate changing based on their personal
      experiences. Commonest source of information about climate change was television
      (59.78%). Poor awareness about UNFCC, Kyoto Protocol and IPCC was found. 549
      (74.90%) respondents commented that deforestation contribute most significantly
      towards climate change. As per 530 (72.31%) respondents water related issues are
      due to changing climate change. According to 529 (72.17%) respondents, direct
      physical hazards of extreme climatic events are most important health related
      impact of climate change. According to 478 (65.21%) respondents, life style
      changes (63.3%) would be most effective in tackling climate change and for
      preventing further climate change. CONCLUSION: The urban general population is
      aware about changing global climate. Personal efforts are more important in
      mitigating climate change as per the urban general population. The awareness
      campaigns regarding mitigation activities are recommended.

PMID- 22412289
TI  - Study to assess the level of stress and identification of significant stressors
      among the railway engine pilots.
AB  - INTRODUCTION: Increasing demands, exacting management, poor ergonomics, and
      intense competition within and without are likely to contribute to stress among
      the railway engine pilots. This excess of stress and its consequences cost very
      high to both the organization and the consumers. AIMS AND OBJECTIVES: This study
      aims to identify the particular stressors affecting the railway engine pilots and
      their level of occupational stress in order to improve the safety, efficiency,
      and overall productivity of the railways and to propose the remedies. MATERIALS
      AND METHODS: A cross-sectional study conducted at Central Hospital, SECR,
      Bilaspur, from 20/09/10 to 20/11/10, involving a study sample of 100 healthy Loco
      Pilots and 100 controls with similar safety category meeting the set inclusion
      and exclusion criteria, subjected to cross-sectional interviews and
      questionnaires. RESULTS: Job stress correlated significantly with fatigue
      (P<0.001), ergonomics of work place (P<0.05) (particularly the postural
      discomfort and cab space), management pressure (P<0.01), high job demand
      (P<0.001), low control and low support at work (P<0.01), biological functions
      (P<0.05), and absenteeism (P<0.001). Top ten stressors have been identified and
      postural discomfort tops the list. The study also identifies minimal efforts from
      administration to reduce stress of its employees. CONCLUSION: The high demand,
      low control, and low support at the work with difficult work environment and
      inadequate recreation at the place of intermediary rest corroborates with
      development of stress affecting the normal biological functions leading to either
      avoidance of duty or making the railway engine pilots susceptible to fatigue and
      drowsiness, neglect, injuries, and accidents.

PMID- 22412290
TI  - Cardiac strain of confectionery worker in relation to heat exposure during
      regular work shift.
AB  - CONTEXT: In India, a wide variety of occupations are performed in adverse indoor
      working environment. Work physiological studies in these jobs are scanty as
      compared to investigations done on more arduous outdoor occupations. AIMS AND
      OBJECTIVES: Physiological strain of workers engaged in sweet making activities
      was assessed in terms of cardiac strain indices in relation to heat stress.
      SETTING AND DESIGN: 33 full-time workers from eastern India were compared for
      cardiac strain profile obtained during summer and winter during their regular
      work shift. A comparison was also done in between younger (n=12) and older (n=16)
      subjects. MATERIALS AND METHODS: Working heart rate (WHR) was recorded
      continuously during work. The pulse deceleration index (PDI) was obtained from
      recovery heart rate (RHR). Net cardiac cost (NCC) and relative cardiac cost (RCC)
      were the main indices used to evaluate physical strain. Thermal stress assessed
      from wet bulb globe temperature (WBGT). STATISTICAL ANALYSIS: Students' t-test
      and Wilcoxon signed rank paired tests were used for comparing physiological
      responses. Values were considered significant when P < 0.05. RESULTS: Work load
      was significantly higher in summer for all workers. RCC of younger workers in
      winter and summer ranged between 18% and 26%. This was significantly lower as
      compared to the RCC of older workers which was 27% in winter and 30% in summer.
      The physiological workload appeared to be moderate in nature. The WBGT index was
      above the recommended range in summer for both the groups. Older workers showed a
      no recovery pattern in terms of recovery pulse that indicated toward a cumulative
      stress which may be attributed to a combined effect of heat and work in summer
      and extra amount of work performed in winter season. CONCLUSION: The physical
      workload is aggravated with various ergonomic stressors present in the work
      place. An ergonomic intervention has been indicated as further scope of this
      study.

PMID- 22412291
TI  - A comparative ergonomic study of work-related upper extremity musculo skeletal
      disorder among the unskilled and skilled surgical blacksmiths in West Bengal,
      India.
AB  - OBJECTIVE: The main aim of the study was to determine the nature and extent of
      work-related upper extremity musculoskeletal disorders (MSDs) and physiological
      stress among the blacksmiths involved in surgical instrument industry. MATERIALS
      AND METHODS: In the present investigation, 50 male blacksmiths of each skilled
      and unskilled groups of the forging section had been selected. For the symptom
      survey, a questionnaire on discomfort symptoms was performed. Repetitiveness of
      work and hand grip strength of both the groups were measured. RESULTS: It was
      revealed that upper limb MSD was a major problem among both group of blacksmith,
      primarily involving the hand, wrist, fingers, and shoulder. From this study it
      was found that 66% (33) skilled and 80% (40) unskilled blacksmith workers are
      feeling discomfort. The most commonly affected regions among the skilled and
      unskilled blacksmith workers were lower back (skilled 65% and unskilled 80%),
      neck (skilled 60% and unskilled 80%), and hand (skilled 50% and unskilled).

PMID- 22412292
TI  - Study of the effects of hydrogen cyanide exposure in Cassava workers.
AB  - BACKGROUND: Hydrogen cyanide is the chemical responsible for tissue hypoxia.
      Chronic exposure to HCN may cause neurological, respiratory, cardiovascular and
      thyroid defects. Onset of symptoms depends on dose and duration of exposure.
      Large scale of Cassava processing could be disastrous due to discharge of
      hydrocyanic acid into the air. Cassava processing is the major industrial work in
      and around Salem. Hence the present study is taken to assess the effects of HCN
      exposure in Cassava workers. MATERIALS AND METHODS: Thirty-nine workers from a
      Cassava processing unit at Salem and age-matched controls of the same economic
      status were taken up for this study. Clinical history was obtained with a
      questionnaire and their Blood sugar, lipid profile, serum total protein, urea,
      creatinine, AST, ALT and T(3), T(4), TSH were estimated using a fasting blood
      sample and AIP was calculated. Statistical analysis was done by student t test.
      RESULTS: Our study reveals a significant increase in triglyceride in Cassava
      workers when compared to the control. Atherogenic index of plasma (AIP) is
      statistically highly significant. A significant decrease was seen in T(4.)
      CONCLUSION: An increase in TGL and AIP shows a higher degree of cardiovascular
      risk. A decrease in T4 suggests an insufficient iodine uptake by thyroid gland.
      Hence a periodic medical evaluation should be done on such workers for their
      safety and to prevent the health hazard.

PMID- 22412293
TI  - Successful intervention in a child with toxic methemoglobinemia due to nail
      polish remover poisoning.
AB  - Children are most susceptible to accidental exposure of common household
      substances and one of the common household substances is nail polish remover. We
      are presenting a case of accidental ingestion of nail polish remover with lethal
      methemoglobinemia (serum methemoglobin level-72%). This patient was treated
      successfully with injection methylene blue. However, even small amounts can be
      dangerous to children, so it is important to keep this and all household
      chemicals in a safe place.

PMID- 22412294
TI  - Working condition: A key factor in increasing occupational hazard among bidi
      rollers: A population health research with respect to DNA damage.
AB  - The present investigation was undertaken to study the role of working conditions
      in occupational hazards among bidi rollers occupationally exposed to tobacco dust
      with reference to DNA damage in peripheral blood lymphocytes. Initially,
      biomonitoring was conducted by estimating urinary thioether to detect the extent
      of xenobiotic exposure, and genotoxicity was evaluated by assessing DNA damage
      and micronucleus frequency in buccal epithelial cells in female bidi rollers
      occupationally exposed to bidi tobacco dust. Student's t-test was used to test
      the significance between the means. Results showed a significant increase in
      urinary thioether level in during-shift urine samples as compared to pre-shift
      samples, which indicated exposure of bidi rollers to xenobiotic compounds. A
      significant increase in DNA damage was observed in the rollers working in
      confined environment as compared to those who worked in open and mixed kind of
      working conditions. Keeping in view the adverse effects of tobacco inhalation on
      the genotoxic effects in bidi rollers as an occupational hazard and in order to
      minimize the hazardous effects, it is recommended that masks should be worn by
      the bidi rollers during work to minimize inhalation of tobacco dust. Gloves
      should be worn particularly if there are bruises etc. in the palm. To minimize
      the absorption through eyes, covered glasses should be worn. The entire process
      of bidi rolling may be done preferably under well ventilated conditions. Due care
      to be taken to sit in the direction facing the direction of wind to avoid
      inhalation of blown away tobacco dust.

PMID- 22412295
TI  - Climate change vulnerability: Index and mapping.

PMID- 22412296
TI  - Assessment of referrals to a multidisciplinary outpatient clinic for patients
      with back pain.
AB  - OBJECTIVE: Each year our multidisciplinary outpatient clinic for patients with
      back pain receives a large number of referrals from primary care physicians,
      manual physiotherapists, and chiropractors. We wanted to assess the quality of
      the referrals regarding the information provided about case history, clinical
      findings, and results from additional investigations. MATERIAL AND METHODS: Two
      hundred and eighty six consecutive referrals received in the time period from 1
      October 2008 to 1 March 2009 were reviewed. We investigated if the referrals
      contained 12 given items. The items were defined by consensus of the broad range
      of specialists working at the multidisciplinary outpatient clinic. All registered
      items were regarded as useful when assigning patients with a priority and
      appropriate caregiver at the outpatient clinic. The 12 items that our group felt
      were reflective of good referrals were information about occupational status,
      duration of symptoms, pain distribution, sensory symptoms, use of analgesics,
      alleviating and/or aggravating factors, systems enquiry (i.e. urination, bowel
      movements, and sleep), provided treatment, deep tendon reflexes, motor function,
      sensory examination, and radiculopathy tests (i.e. straight leg raise and/or
      foraminal compression test). RESULTS: Two hundred and fifty six (89.5%) referrals
      were from primary care physicians, and the remaining came from physicians in
      internships, manual physiotherapists, and chiropractors. Six (2.1%) referrals
      contained all 12 items. On average each referral contained 5.95 items (95% CI:
      5.66-6.25). Information about analgesics, sensory symptoms, systems enquiry, and
      alleviating and aggravating factors was most frequently missing. Information
      about provided treatment, motor function, deep tendon reflexes, clinical tests,
      and occupational status was included in about half of the referrals. In 27.3% of
      the referrals from primary care physicians information about clinical findings
      was missing. Referrals from manual physiotherapists contained statistically
      significant more information (9.67 items, 95% CI: 7.63-11.70) than from the other
      groups (P<0.001). The number of patients registered with each primary care
      physician did not affect the number of items in the referrals. CONCLUSION: Many
      of the referrals were inadequate. Inadequate referrals can lead to prolonged
      waiting time for examination and treatment. Referrals with relevant information
      about patient history and clinical findings are essential in order to assign
      patients with an appropriate caregiver at the outpatient clinic and to determine
      if and which diagnostic imaging findings are of clinical relevance.

PMID- 22412297
TI  - Functionalization of single-walled carbon nanotubes and their binding to cancer
      cells.
AB  - BACKGROUND: Single-walled carbon nanotubes (SWCNTs) have novel properties
      including their nanoscale size and ease of cellular uptake. This makes them
      useful for drug delivery, and their photo-thermal effects make them potentially
      useful in a wide range of applications, particularly the treatment of solid
      tumors. The poor solubility of SWCNTs has, however, been an issue that may
      potentially limit the utility of SWCNTs for cancer treatment. Functionalization
      of the surface of the tubes may be an approach to overcome this problem. METHODS:
      SWCNTs were refluxed in HNO3/H2SO4 (1:3) at 120 degrees C for 120 minutes.
      Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy
      (FTIR), contact angle measurements, and near infrared (NIR) light exposure were
      used to assess the functionalization process. The attachment of a carbohydrate
      binding protein (lectin) labeled with fluorescein isothiocyanate to the
      functionalized SWCNTs enabled evaluation of the functionalization step via
      confocal microscopy. The lectin from Helix pomatia, (Helix pomatia agglutinin
      [HPA]), can detect changes in protein glycosylation associated with aggressive
      metastatic cancer. The interaction between the lectin HPA alone and HPA
      conjugated to the functionalized SWCNTs with human breast cancer cells (MCF-7)
      was measured using a quartz crystal microbalance biosensor. RESULTS: Following
      the functionalization process, TEM images showed a layer had formed on the
      surface of the SWCNTs. In the FTIR experiment, results illustrated the presence
      of the -COOH group on the functionalized SWCNTs. Contact angle measurements
      showed that upon functionalization the hydrophilicity of the SWCNTs increased.
      The temperature increase in the liquid (supernatant) surrounding the
      functionalized SWCNTs following exposure to light in the NIR (808 nm) was greater
      than for non-functionalized SWCNTs. The biosensor work showed that HPA binds with
      high affinity (nanomolar range) to human breast cancer cells; HPA-binding
      properties to MCF-7 cells were retained following conjugation to the
      functionalized SWCNTs. CONCLUSION: Treating pure SWCNTs with HNO3/H2SO4 (1:3) at
      120 degrees C for 120 minutes is an effective method for functionalization of
      SWCNTs. HPA linked to SWCNTs is a suitable candidate for the delivery of the
      functionalized SWCNTs to cancer cells.

PMID- 22412298
TI  - RGD-conjugated gold nanorods induce radiosensitization in melanoma cancer cells
      by downregulating alpha(v)beta3 expression.
AB  - BACKGROUND: Melanoma is known to be radioresistant and traditional treatments
      have been intractable. Therefore, novel approaches are required to improve the
      therapeutic efficacy of melanoma treatment. In our study, gold nanorods
      conjugated with Arg-Gly-Asp peptides (RGD-GNRs) were used as a sensitizer to
      enhance the response of melanoma cells to 6 mV radiation. METHODS AND MATERIALS:
      A375 melanoma cells were treated by gold nanorods or RGD-GNRs with or without
      irradiation. The antiproliferative impact of the treatments was measured by MTT
      assay. Radiosensitizing effects were determined by colony formation assay.
      Apoptosis and cell cycle data were measured by flow cytometry. Integrin
      alpha(v)beta3 expression was also investigated by flow cytometry. RESULTS:
      Addition of RGD-GNRs enhanced the radiosensitivity of A375 cells with a dose
      modifying factor of 1.35, and enhanced radiation-induced apoptosis. DNA flow
      cytometric analysis indicated that RGD-GNRs plus irradiation induced significant
      G2/M phase arrest in A375 cells. Both spontaneous and radiation-induced
      expressions of integrin alpha(v)beta3 were downregulated by RGD-GNRs. CONCLUSION:
      Our study indicated that RGD-GNRs could sensitize melanoma A375 cells to
      irradiation. It was hypothesized that this was mainly through downregulation of
      radiation-induced alpha(v)beta3, in addition to induction of a higher proportion
      of cells within the G2/M phase. The combination of RGD-GNRs and radiation needs
      further investigation.

PMID- 22412299
TI  - Protection of adenovirus from neutralizing antibody by cationic PEG derivative
      ionically linked to adenovirus.
AB  - BACKGROUND: The generation of anti-adenovirus neutralizing antibody (NAb) in
      humans severely restricts the utilization of recombinant adenovirus serotype 5
      (Ad5) vectors in gene therapy for a wide range of clinical trials. To overcome
      this limitation, we ionically complexed Ad5 with a newly synthesized copolymer,
      which we called APC, making an adenovirus shielded from NAb. METHODS: APC, a
      cationic polyethylene glycol derivative, was synthesized via two steps of ring
      opening copolymerization of ethylene oxide and allyl glycidyl ether, followed by
      the addition of 2-mercaptoethylamine. The copolymer or the control PEI-2k was
      ionically complexed to anionic Ad5 in 5% glucose, and in vitro transduction
      assays were carried out in coxsackievirus and adenovirus receptor-positive cells
      (A549) and coxsackievirus and adenovirus receptor-negative cells (B16 and SKOV3).
      The physical properties and morphology of adenovirus alone or the complexes were
      investigated respectively by zeta potential, size distribution, and transmission
      electron microscopy image. Then cytotoxicity of APC was examined using 3-[4, 5
      dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assays. Finally, the
      ability of APC to protect adenovirus from NAb was evaluated by transfection
      assays after a neutralizing effect. RESULTS: APC was successfully synthesized and
      showed a low cytotoxicity. Positively charged Ad5/APC exhibited slightly
      increased diameter (130.2 +/- 0.60 nm) than naked Ad5 (115.6 +/- 5.46 nm) while
      Ad5/PEI-2k showed severe aggregation (1382 +/- 79.9 nm). Ad5/APC achieved a gene
      transfection level as high as Ad5/PEI-2k in A549 or B16 cells, and significantly
      higher than Ad5/PEI-2k in SKOV3 cells. Most importantly, after the exposure to
      the neutralizing antibody, naked Ad5 and Ad5/PEI-2k exhibited poor gene
      expression while Ad5/APC still showed significantly efficient gene expression.
      CONCLUSION: Our results demonstrated that Ad5/APC complex offered good protection
      for Ad5 against NAb in vitro and suggested a potential strategy of resistance to
      NAb in vivo.

PMID- 22412300
TI  - Liposomes prolong the therapeutic effect of anti-asthmatic medication via
      pulmonary delivery.
AB  - PURPOSE: The main objective of this study was to develop a novel aerosolized
      liposome formulation for pulmonary delivery of anti-asthmatic medication and to
      explore the relationship between the bioavailability and anti-asthmatic efficacy
      of such a formulation. Asthma treatment usually requires frequent administration
      of medication for sustained bronchodilating response. Liposomes are known for
      their capability for sustained drug release and thus would be a suitable delivery
      system for anti-asthmatic medication for prolonged therapeutic effect. Salbutamol
      sulfate (SBS) was chosen as the model drug in this study because of its high
      water solubility and fast absorption after administration. METHODS: SBS was
      efficiently encapsulated into liposomes by the vesicular phospholipid gel
      technique. SBS permeability across the pulmonary membrane of an Asian toad was
      determined by in vitro study. Intratracheal administration of liposomes labeled
      with the fluorescent dye 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide
      (DiR) in a rat model was assessed by a small animal imaging system and
      pharmacokinetic analysis. Pharmacodynamic analysis was performed in guinea pigs
      using the Konzett-Rossler method. RESULTS: SBS was efficiently encapsulated into
      liposomes with encapsulation efficiency as high as 70%. The particle size of the
      SBS liposome suspension was approximately 57 +/- 21 nm. In the in vitro study of
      permeability across the pulmonary membrane of Asian toads, SBS from liposomes
      demonstrated a slower transport rate compared to free SBS solution. Pulmonary
      delivery of liposomes in a rat model showed that the liposomes were effectively
      distributed in the respiratory tract and lungs, and that the release of SBS from
      liposomes was sustained for at least 48 hours. Pharmacodynamic analysis in a
      guinea pig model showed that the anti-asthmatic effect of SBS liposomes persisted
      for up to 18 hours, whereas that of free SBS solution was less than 8 hours.
      CONCLUSION: The overall results demonstrated that liposomes could increase the
      concentration and retention time of SBS in the lungs and therefore prolong its
      therapeutic effect.

PMID- 22412301
TI  - Degradable polyethylenimine derivate coupled to a bifunctional peptide R13 as a
      new gene-delivery vector.
AB  - BACKGROUND: To solve the efficiency versus cytotoxicity and tumor-targeting
      problems of polyethylenimine (PEI) used as a nonviral gene delivery vector, a
      degradable PEI derivate coupled to a bifunctional peptide R13 was developed.
      METHODS: First, we synthesized a degradable PEI derivate by crosslinking low
      molecular-weight PEI with pluronic P123, then used tumor-targeting peptide
      arginine-glycine-aspartate-cysteine (RGDC), in conjunction with the cell
      penetrating peptide Tat (49-57), to yield a bifunctional peptide RGDC-Tat (49-57)
      named R13, which can improve cell selection and increase cellular uptake, and,
      lastly, adopted R13 to modify the PEI derivates so as to prepare a new polymeric
      gene vector (P123-PEI-R13). The new gene vector was characterized in terms of its
      chemical structure and biophysical parameters. We also investigated the
      specificity, cytotoxicity, and gene transfection efficiency of this vector in
      alphavbeta3-positive human cervical carcinoma Hela cells and murine melanoma B16
      cells in vitro. RESULTS: The vector showed controlled degradation, strong
      targeting specificity to alphavbeta3 receptor, and noncytotoxicity in Hela cells
      and B16 cells at higher doses, in contrast to PEI 25 KDa. The particle size of
      P123-PEI-R13/DNA complexes was around 100-250 nm, with proper zeta potential. The
      nanoparticles can protect plasmid DNA from being digested by DNase I at a
      concentration of 6 U DNase I/MUg DNA. The nanoparticles were resistant to
      dissociation induced by 50% fetal bovine serum and 600 MUg/mL sodium heparin.
      P123-PEI-R13 also revealed higher transfection efficiency in two cell lines as
      compared with PEI 25 KDa. CONCLUSION: P123-PEI-R13 is a potential candidate as a
      safe and efficient gene-delivery carrier for gene therapy.

PMID- 22412302
TI  - Balloon Valvuloplasty of Aortic Valve Stenosis in Childhood: Midterm Results in a
      Children's Hospital, Mansoura University, Egypt.
AB  - BACKGROUND: Balloon valvuloplasty was established as an alternative to surgery
      for treatment of aortic valve stenosis in childhood. Acute complications after
      balloon dilatation including aortic insufficiency or early death were described.
      AIM OF WORK: To analyze early outcome and midterm results of balloon aortic
      valvuloplasty (BAV) in Children's Hospital, Mansoura University, Egypt. SUBJECTS
      AND METHODS: Between April 2005-June 2008, all consecutive patients of age <18
      years treated for aortic valve stenosis (AVS) with BAV were analyzed
      retrospectively. The study included 21 patients; 17 males, and 4 females. Their
      age ranged from the neonatal period to 10 years (mean age 5.6 +/- 3.7 years).
      Patients with gradient >=50 mmHg and aortic valve insufficiency (AI) up to grade
      I were included. All patients had isolated aortic valve stenosis except 3
      patients (14.3%) had associated aortic coarctation. Six patients (28.6%) had
      bicuspid aortic valve. All patients had normal myocardial function except one
      (4.8%) had FS 15%. The duration of follow up was (mean +/- SD: 18.5 +/- 11.7
      months). RESULTS: Femoral artery approach was used in 20 patients (95.2%) and
      carotid artery in one neonate (4.8%). Balloon/annulus ratio was 0.83 +/- 0.04.
      Significant reduction in pressure gradient was achieved (mean 66.7 +/- 9.8 mmHg
      to 20.65 +/- 2.99 mmHg) (P < 0.001). Nine patients (42.8%) developed grade I AI,
      2 patients (9.5%) developed grade II AI and 1 patient (4.8%) developed grade III
      AI. Two early deaths (9.5%); one died due to heart failure caused by grade IV AI
      and a neonate died because of severely compromised LV function. One patient
      (4.8%) had femoral artery occlusion necessitating anticoagulation. Patients
      remained free from re-intervention during follow up. CONCLUSION: Balloon
      valvuloplasty of aortic valve stenosis significantly reduces gradient with low
      morbidity and mortality in children.

PMID- 22412303
TI  - Safety and efficacy of pemetrexed in maintenance therapy of non-small cell lung
      cancer.
AB  - Lung cancer incidence continues to rise and is the number one cause of cancer
      death in both men and women worldwide with projected 221,130 new cases and
      156,940 deaths in the United States in 2011.1 Non-small cell lung cancer (NSCLC)
      represents more than 85% of the cases with most patients having either locally
      advanced or metastatic disease at the time of initial diagnosis, and
      approximately 60%-70% of them have an adenocarcinoma histologic subtype. In the
      last three years, we have seen several advances in the management of NSCLC, with
      several factors playing an important role in the treatment decision making
      process. Maintenance therapy has been added to the algorithm of NSCLC management
      and Pemetrexed has been studied as single agent or in combination in this setting
      with recent studies showing safety and improved progression free survival (PFS)
      and/or overall survival (OS), still the disease for the most part has a dismal
      outcome. More research work needs to be done to identify which patients truly
      benefit from these approaches, and to whom we should offer maintenance or switch
      maintenance vs. close observation.

PMID- 22412304
TI  - Artificial Roughness Encoding with a Bio-inspired MEMS- based Tactile Sensor
      Array.
AB  - A compliant 2*2 tactile sensor array was developed and investigated for roughness
      encoding. State of the art cross shape 3D MEMS sensors were integrated with
      polymeric packaging providing in total 16 sensitive elements to external
      mechanical stimuli in an area of about 20 mm(2), similarly to the SA1 innervation
      density in humans. Experimental analysis of the bio-inspired tactile sensor array
      was performed by using ridged surfaces, with spatial periods from 2.6 mm to 4.1
      mm, which were indented with regulated 1N normal force and stroked at constant
      sliding velocity from 15 mm/s to 48 mm/s. A repeatable and expected frequency
      shift of the sensor outputs depending on the applied stimulus and on its scanning
      velocity was observed between 3.66 Hz and 18.46 Hz with an overall maximum error
      of 1.7%. The tactile sensor could also perform contact imaging during static
      stimulus indentation. The experiments demonstrated the suitability of this
      approach for the design of a roughness encoding tactile sensor for an artificial
      fingerpad.

PMID- 22412305
TI  - Use of human senses as sensors.
AB  - This paper is an overview of our recent findings obtained by the use of human
      senses as sensors, suggesting that human senses might be indispensable sensors,
      not only for practical uses but also for gaining a deeper understanding of
      humans. From this point of view, two kinds of studies, both based on semantic
      responses of participants, deserve emphasis. One study assessed the efficacy of
      the photocatalytic elimination of stains or bio-aerosols from an air environment
      using TiO(2) as well as the photocatalytic deodorizing efficacy of a TiO(2)-type
      deodorizer; the other study evaluated the changes in perception of a given aroma
      while inhaling the fragrance of essential oils. In the latter study, we employed
      a sensory test for evaluating changes in perception of a given aroma. Sensory
      tests were conducted twice, when participants were undergoing the Kraepelin
      mental performance test (mental arithmetic) or an auditory task (listening to
      environmental natural sounds), once before the task (pre-task) and once after the
      task (post-task). The perception of fragrance was assessed by 13 contrasting
      pairs of adjectives as a function of the task assigned to participants. The
      obtained findings illustrate subtle nuances regarding how essential oils manifest
      their potency and how olfactory discrimination and responses occur in humans.

PMID- 22412306
TI  - Detection of Gaseous Plumes using Basis Vectors.
AB  - Detecting and identifying weak gaseous plumes using thermal imaging data is
      complicated by many factors. There are several methods currently being used to
      detect plumes. They can be grouped into two categories: those that use a chemical
      spectral library and those that don't. The approaches that use chemical libraries
      include physics-based least squares methods (matched filter). They are "optimal"
      only if the plume chemical is actually in the search library but risk missing
      chemicals not in the library. The methods that don't use a chemical spectral
      library are based on a statistical or data analytical transformation applied to
      the data. These include principle components, independent components, entropy,
      Fourier transform, and others. These methods do not explicitly take advantage of
      the physics of the signal formulation process and therefore don't exploit all
      available information in the data. This paper describes generalized least squares
      detection using gas spectra, presents a new detection method using basis vectors,
      and compares detection images resulting from applying both methods to synthetic
      hyperspectral data.

PMID- 22412308
TI  - Development of 3D Force Sensors for Nanopositioning and Nanomeasuring Machine.
AB  - In this contribution, we report on different miniaturized bulk micro machined
      three-axes piezoresistive force sensors for nanopositioning and nanomeasuring
      machine (NPMM). Various boss membrane structures, such as one boss full/cross,
      five boss full/cross and swastika membranes, were used as a basic structure for
      the force sensors. All designs have 16 p-type diffused piezoresistors on the
      surface of the membrane. Sensitivities in x, y and z directions are measured.
      Simulated and measured stiffness ratio in horizontal to vertical direction is
      measured for each design. Effect of the length of the stylus on H:V stiffness
      ratio is studied. Minimum and maximum deflection and resonance frequency are
      measured for all designs. The sensors were placed in a nanopositioning and
      nanomeasuring machine and one point measurements were performed for all the
      designs. Lastly the application of the sensor is shown, where dimension of a cube
      is measured using the sensor.

PMID- 22412307
TI  - Methodology and Significance of Microsensor-based Oxygen Mapping in Plant Seeds -
      an Overview.
AB  - Oxygen deficiency is commonplace in seeds, and limits both their development and
      their germination. It is, therefore, of considerable relevance to crop
      production. While the underlying physiological basis of seed hypoxia has been
      known for some time, the lack of any experimental means of measuring the global
      or localized oxygen concentration within the seed has hampered further progress
      in this research area. The development of oxygen-sensitive microsensors now
      offers the capability to determine the localized oxygen status within a seed, and
      to study its dynamic adjustment both to changes in the ambient environment, and
      to the seed's developmental stage. This review illustrates the use of oxygen
      microsensors in seed research, and presents an overview of existing data with an
      emphasis on crop species. Oxygen maps, both static and dynamic, should serve to
      increase our basic understanding of seed physiology, as well as to facilitate
      upcoming breeding and biotechnology-based approaches for crop improvement.

PMID- 22412309
TI  - Development of a sensor node for precision horticulture.
AB  - This paper presents the design of a new wireless sensor node (GAIA Soil-Mote) for
      precision horticulture applications which permits the use of precision
      agricultural instruments based on the SDI-12 standard. Wireless communication is
      achieved with a transceiver compliant with the IEEE 802.15.4 standard. The GAIA
      Soil-Mote software implementation is based on TinyOS. A two-phase methodology was
      devised to validate the design of this sensor node. The first phase consisted of
      laboratory validation of the proposed hardware and software solution, including a
      study on power consumption and autonomy. The second phase consisted of
      implementing a monitoring application in a real broccoli (Brassica oleracea L.
      var Marathon) crop in Campo de Cartagena in south-east Spain. In this way the
      sensor node was validated in real operating conditions. This type of application
      was chosen because there is a large potential market for it in the farming
      sector, especially for the development of precision agriculture applications.

PMID- 22412310
TI  - Comparison of Low Cost Miniature Spectrometers for Volcanic SO(2) Emission
      Measurements.
AB  - Miniature ultraviolet USB coupled spectrometers have become ubiquitously applied
      over the last decade for making volcanic SO(2) emission rate measurements. The
      dominantly applied unit has recently been discontinued however, raising the
      question of which currently available devices should now be implemented. In this
      paper, we consider, and make recommendations on this matter, by studying a number
      of inexpensive compact spectrometers in respect of measurement performance and
      thermal behaviour. Of the studied units, the Avaspec demonstrated the best
      prospects for the highest time resolution applications, but in the majority of
      cases, we anticipate users likely preferring the less bulky USB2000+s.

PMID- 22412311
TI  - Evaluation of cartosat-1 multi-scale digital surface modelling over france.
AB  - On 5 May 2005, the Indian Space Research Organization launched Cartosat-1, the
      eleventh satellite of its constellation, dedicated to the stereo viewing of the
      Earth's surface for terrain modeling and large-scale mapping, from the Satish
      Dhawan Space Centre (India). In early 2006, the Indian Space Research
      Organization started the Cartosat-1 Scientific Assessment Programme, jointly
      established with the International Society for Photogrammetry and Remote Sensing.
      Within this framework, this study evaluated the capabilities of digital surface
      modeling from Cartosat-1 stereo data for the French test sites of Mausanne les
      Alpilles and Salon de Provence. The investigation pointed out that for hilly
      territories it is possible to produce high-resolution digital surface models with
      a root mean square error less than 7.1 m and a linear error at 90% confidence
      level less than 9.5 m. The accuracy of the generated digital surface models also
      fulfilled the requirements of the French Reference 3D(r), so Cartosat-1 data may
      be used to produce or update such kinds of products.

PMID- 22412312
TI  - A procedure for high resolution satellite imagery quality assessment.
AB  - Data products generated from High Resolution Satellite Imagery (HRSI) are
      routinely evaluated during the so-called in-orbit test period, in order to verify
      if their quality fits the desired features and, if necessary, to obtain the image
      correction parameters to be used at the ground processing center. Nevertheless,
      it is often useful to have tools to evaluate image quality also at the final user
      level. Image quality is defined by some parameters, such as the radiometric
      resolution and its accuracy, represented by the noise level, and the geometric
      resolution and sharpness, described by the Modulation Transfer Function (MTF).
      This paper proposes a procedure to evaluate these image quality parameters; the
      procedure was implemented in a suitable software and tested on high resolution
      imagery acquired by the QuickBird, WorldView-1 and Cartosat-1 satellites.

PMID- 22412313
TI  - Effects of Anode Flow Field Design on CO(2) Bubble Behavior in MUDMFC.
AB  - Clogging of anode flow channels by CO(2) bubbles is a vital problem for further
      performance improvements of the micro direct methanol fuel cell (MUDMFC). In this
      paper, a new type anode structure using the concept of the non-equipotent
      serpentine flow field (NESFF) to solve this problem was designed, fabricated and
      tested. Experiments comparing the MUDMFC with and without this type of anode flow
      field were implemented using a home-made test loop. Results show that the mean
      value, amplitude and frequency of the inlet-to-outlet pressure drops in the NESFF
      is far lower than that in the traditional flow fields at high MUDMFC output
      current. Furthermore, the sequential images of the CO(2) bubbles as well as the
      MUDMFC performance with different anode flow field pattern were also
      investigated, and the conclusions are in accordance with those derived from the
      pressure drop experiments. Results of this study indicate that the non-equipotent
      design of the MUDMFC anode flow field can effectively mitigate the CO(2) clogging
      in the flow channels, and hence lead to a significant promotion of the MUDMFC
      performance.

PMID- 22412314
TI  - A miniature probe for ultrasonic penetration of a single cell.
AB  - Although ultrasound cavitation must be avoided for safe diagnostic applications,
      the ability of ultrasound to disrupt cell membranes has taken on increasing
      significance as a method to facilitate drug and gene delivery. A new ultrasonic
      resonance driving method is introduced to penetrate rigid wall plant cells or
      oocytes with springy cell membranes. When a reasonable design is created,
      ultrasound can gather energy and increase the amplitude factor. Ultrasonic
      penetration enables exogenous materials to enter cells without damaging them by
      utilizing instant acceleration. This paper seeks to develop a miniature
      ultrasonic probe experiment system for cell penetration. A miniature ultrasonic
      probe is designed and optimized using the Precise Four Terminal Network Method
      and Finite Element Method (FEM) and an ultrasonic generator to drive the probe is
      designed. The system was able to successfully puncture a single fish cell.

PMID- 22412315
TI  - Optical and Electronic NO(x) Sensors for Applications in Mechatronics.
AB  - Current production and emerging NO(x) sensors based on optical and nanomaterials
      technologies are reviewed. In view of their potential applications in
      mechatronics, we compared the performance of: i) Quantum cascade lasers (QCL)
      based photoacoustic (PA) systems; ii) gold nanoparticles as catalytically active
      materials in field-effect transistor (FET) sensors, and iii) functionalized III-V
      semiconductor based devices. QCL-based PA sensors for NO(x) show a detection
      limit in the sub part-per-million range and are characterized by high selectivity
      and compact set-up. Electrochemically synthesized gold-nanoparticle FET sensors
      are able to monitor NO(x) in a concentration range from 50 to 200 parts per
      million and are suitable for miniaturization. Porphyrin-functionalized III-V
      semiconductor materials can be used for the fabrication of a reliable NO(x)
      sensor platform characterized by high conductivity, corrosion resistance, and
      strong surface state coupling.

PMID- 22412316
TI  - Mechanical-thermal noise in drive-mode of a silicon micro-gyroscope.
AB  - A new closed-loop drive scheme which decouples the phase and the gain of the
      closed-loop driving system was designed in a Silicon Micro-Gyroscope (SMG). We
      deduce the system model of closed-loop driving and use stochastic averaging to
      obtain an approximate "slow" system that clarifies the effect of thermal noise.
      The effects of mechanical-thermal noise on the driving performance of the SMG,
      including the noise spectral density of the driving amplitude and frequency, are
      derived. By calculating and comparing the noise amplitude due to thermal noise
      both in the opened-loop driving and in the closed-loop driving, we find that the
      closed-loop driving does not reduce the RMS noise amplitude. We observe that the
      RMS noise frequency can be reduced by increasing the quality factor and the drive
      amplitude in the closed-loop driving system. The experiment and simulation
      validate the feasibility of closed-loop driving and confirm the validity of the
      averaged equation and its stablility criterion. The experiment and simulation
      results indicate the electrical noise of closed-loop driving circuitry is bigger
      than the mechanical-thermal noise and as the driving mass decreases, the
      mechanical-thermal noise may get bigger than the electrical noise of the closed
      loop driving circuitry.

PMID- 22412317
TI  - A real-time spectroscopic sensor for monitoring laser welding processes.
AB  - In this paper we report on the development of a sensor for real time monitoring
      of laser welding processes based on spectroscopic techniques. The system is based
      on the acquisition of the optical spectra emitted from the laser generated plasma
      plume and their use to implement an on-line algorithm for both the calculation of
      the plasma electron temperature and the analysis of the correlations between
      selected spectral lines. The sensor has been patented and it is currently
      available on the market.

PMID- 22412318
TI  - Intelligent foreign particle inspection machine for injection liquid examination
      based on modified pulse-coupled neural networks.
AB  - A biologically inspired spiking neural network model, called pulse-coupled neural
      networks (PCNN), has been applied in an automatic inspection machine to detect
      visible foreign particles intermingled in glucose or sodium chloride injection
      liquids. Proper mechanisms and improved spin/stop techniques are proposed to
      avoid the appearance of air bubbles, which increases the algorithms' complexity.
      Modified PCNN is adopted to segment the difference images, judging the existence
      of foreign particles according to the continuity and smoothness properties of
      their moving traces. Preliminarily experimental results indicate that the
      inspection machine can detect the visible foreign particles effectively and the
      detection speed, accuracy and correct detection rate also satisfying the needs of
      medicine preparation.

PMID- 22412319
TI  - Determining the best sensing coverage for 2-dimensional acoustic target tracking.
AB  - Distributed acoustic target tracking is an important application area of wireless
      sensor networks. In this paper we use algebraic geometry to formally model 2
      dimensional acoustic target tracking and then prove its best degree of required
      sensing coverage. We present the necessary conditions for three sensing coverage
      to accurately compute the spatio-temporal information of a target object.
      Simulations show that 3-coverage accurately locates a target object only in 53%
      of cases. Using 4-coverage, we present two different methods that yield correct
      answers in almost all cases and have time and memory usage complexity of
      Theta(1). Analytic 4-coverage tracking is our first proposed method that solves a
      simultaneous equation system using the sensing information of four sensor nodes.
      Redundant answer fusion is our second proposed method that solves at least two
      sets of simultaneous equations of target tracking using the sensing information
      of two different sets of three sensor nodes, and fusing the results using a new
      customized formal majority voter. We prove that 4-coverage guarantees accurate 2
      dimensional acoustic target tracking under ideal conditions.

PMID- 22412320
TI  - A butyl methacrylate monolithic column prepared in-situ on a microfluidic chip
      and its applications.
AB  - A butyl methacrylate (BMA) monolithic column was polymerized in-situ with UV
      irradiation in an ultraviolet transparent PDMS micro-channel on a homemade micro
      fluidic chip. Under the optimized conditions and using a typical polymerization
      mixture consisting of 75% porogenic solvents and 25% monomers, the BMA monolithic
      column was obtained as expected. The BET surface area ratio of the BMA monolithic
      column was 366 m(2).g(-1). The corresponding SEM images showed that the
      monolithic column material polymerized in a glass channel was composed of uniform
      pores and spherical particles with diameters ranging from 3 to 5 MUm. The
      promethazine-luminal-potassium ferricyanide chemiluminescence system was selected
      for testing the capability of the column. A flow injection analytical technique
      chemiluminescence (FIA-CL) system on the microfluidic chip with a BMA monolithic
      column pretreatment unit was established to determine promethazine. Trace
      promethazine was enriched by the BMA monolithic column, with more than a 10-fold
      average enrichment ratio. The proposed method has a linear response concentration
      range of 1.0*10(-8) - 1.0*10(-6)g.mL(-1) and the detection limit was 1.6*10(
      9)g.mL(-1).

PMID- 22412321
TI  - RIDES: Robust Intrusion Detection System for IP-Based Ubiquitous Sensor Networks.
AB  - The IP-based Ubiquitous Sensor Network (IP-USN) is an effort to build the
      "Internet of things". By utilizing IP for low power networks, we can benefit from
      existing well established tools and technologies of IP networks. Along with many
      other unresolved issues, securing IP-USN is of great concern for researchers so
      that future market satisfaction and demands can be met. Without proper security
      measures, both reactive and proactive, it is hard to envisage an IP-USN realm. In
      this paper we present a design of an IDS (Intrusion Detection System) called
      RIDES (Robust Intrusion DEtection System) for IP-USN. RIDES is a hybrid intrusion
      detection system, which incorporates both Signature and Anomaly based intrusion
      detection components. For signature based intrusion detection this paper only
      discusses the implementation of distributed pattern matching algorithm with the
      help of signature-code, a dynamically created attack-signature identifier. Other
      aspects, such as creation of rules are not discussed. On the other hand, for
      anomaly based detection we propose a scoring classifier based on the SPC
      (Statistical Process Control) technique called CUSUM charts. We also investigate
      the settings and their effects on the performance of related parameters for both
      of the components.

PMID- 22412322
TI  - Feasibility studies on si-based biosensors.
AB  - The aim of this paper is to summarize the efforts carried out so far in the
      fabrication of Si-based biosensors by a team of researchers in Catania, Italy.
      This work was born as a collaboration between the Catania section of the
      Microelectronic and Microsystem Institute (IMM) of the CNR, the Surfaces and
      Interfaces laboratory (SUPERLAB) of the Consorzio Catania Ricerche and two
      departments at the University of Catania: the Biomedical Science and the
      Biological Chemistry and Molecular Biology Departments. The first goal of our
      study was the definition and optimization of an immobilization protocol capable
      of bonding the biological sensing element on a Si-based surface via covalent
      chemical bonds. We chose SiO(2) as the anchoring surface due to its
      biocompatibility and extensive presence in microelectronic devices. The
      immobilization protocol was tested and optimized, introducing a new step, oxide
      activation, using techniques compatible with microelectronic processing. The
      importance of the added step is described by the experimental results. We also
      tested different biological molecule concentrations in the immobilization
      solutions and the effects on the immobilized layer. Finally a MOS-like structure
      was designed and fabricated to test an electrical transduction mechanism. The
      results obtained so far and the possible evolution of the research field are
      described in this review paper.

PMID- 22412323
TI  - Progress in the Development of CdTe and CdZnTe Semiconductor Radiation Detectors
      for Astrophysical and Medical Applications.
AB  - Over the last decade, cadmium telluride (CdTe) and cadmium zinc telluride
      (CdZnTe) wide band gap semiconductors have attracted increasing interest as X-ray
      and gamma ray detectors. Among the traditional high performance spectrometers
      based on silicon (Si) and germanium (Ge), CdTe and CdZnTe detectors show high
      detection efficiency and good room temperature performance and are well suited
      for the development of compact and reliable detection systems. In this paper, we
      review the current status of research in the development of CdTe and CdZnTe
      detectors by a comprehensive survey on the material properties, the device
      characteristics, the different techniques for improving the overall detector
      performance and some major applications. Astrophysical and medical applications
      are discussed, pointing out the ongoing Italian research activities on the
      development of these detectors.

PMID- 22412324
TI  - Laser-self-mixing interferometry for mechatronics applications.
AB  - We report on the development of an all-interferometric optomechatronic sensor for
      the detection of multi-degrees-of-freedom displacements of a remote target. The
      prototype system exploits the self-mixing technique and consists only of a laser
      head, equipped with six laser sources, and a suitably designed reflective target.
      The feasibility of the system was validated experimentally for both single or
      multi-degrees-of-freedom measurements, thus demonstrating a simple and
      inexpensive alternative to costly and bulky existing systems.

PMID- 22412325
TI  - Micro-pattern guided adhesion of osteoblasts on diamond surfaces.
AB  - Microscopic chemical patterning of diamond surfaces by hydrogen and oxygen
      surface atoms is used for self-assembly of human osteoblastic cells into micro
      arrays. The cell adhesion and assembly is further controlled by concentration of
      cells (2,500-10,000 cells/cm(2)) and fetal bovine serum (0-15%). The cells are
      characterized by fluorescence microscopy of actin fibers and nuclei. The serum
      protein adsorption is studied by atomic force microscopy (AFM). The cells are
      arranged selectively on O-terminated patterns into 30-200 MUm wide arrays. Higher
      cell concentrations allow colonization of unfavorable H-terminated regions due to
      mutual cell communication. There is no cell selectivity without the proteins in
      the medium. Based on the AFM, the proteins are present on both H- and O
      terminated surfaces. Pronounced differences in their thickness, surface
      roughness, morphology, and phase images indicate different conformation of the
      proteins and explain the cell selectivity.

PMID- 22412326
TI  - Deployment design of wireless sensor network for simple multi-point surveillance
      of a moving target.
AB  - In this paper, we focus on the problem of tracking a moving target in a wireless
      sensor network (WSN), in which the capability of each sensor is relatively
      limited, to construct large-scale WSNs at a reasonable cost. We first propose two
      simple multi-point surveillance schemes for a moving target in a WSN and
      demonstrate that one of the schemes can achieve high tracking probability with
      low power consumption. In addition, we examine the relationship between tracking
      probability and sensor density through simulations, and then derive an
      approximate expression representing the relationship. As the results, we present
      guidelines for sensor density, tracking probability, and the number of monitoring
      sensors that satisfy a variety of application demands.

PMID- 22412327
TI  - Monitoring Animal Behaviour and Environmental Interactions Using Wireless Sensor
      Networks, GPS Collars and Satellite Remote Sensing.
AB  - Remote monitoring of animal behaviour in the environment can assist in managing
      both the animal and its environmental impact. GPS collars which record animal
      locations with high temporal frequency allow researchers to monitor both animal
      behaviour and interactions with the environment. These ground-based sensors can
      be combined with remotely-sensed satellite images to understand animal-landscape
      interactions. The key to combining these technologies is communication methods
      such as wireless sensor networks (WSNs). We explore this concept using a case
      study from an extensive cattle enterprise in northern Australia and demonstrate
      the potential for combining GPS collars and satellite images in a WSN to monitor
      behavioural preferences and social behaviour of cattle.

PMID- 22412328
TI  - Metal Ion Enhanced Charge Transfer in a Terpyridine-bis-Pyrene System.
AB  - The synthesis, electrochemical and photophysical properties of a branched
      molecule 3,5-bis(pyrene-1-yl)-4'-phenyl-2,2':6',2"-terpyridine are reported.
      Spectroscopy in different solvents reveals that an optical electron transfer from
      the pyrene donor to the terpyridyl electron acceptor can occur in polar media, as
      the system displays both charge transfer (CT) absorption and CT emission.
      Furthermore, the study of the zinc complex as well as the bis-protonated form
      shows an enhancement of the electron transfer character of the system, by an
      increase of the acceptor strength. This is accompanied by a large increase of the
      non-radiative processes. With sub-nanosecond transient absorption spectroscopy,
      the CT state, consisting of the pyrene radical cation and the terpyridine radical
      anion, has been detected. At room temperature, the study of the nanosecond
      transient absorption spectra reveals the formation of a low-lying triplet excited
      state that we attribute to the pyrene moiety through which the CT state decays.
      At 77K, the absence of the terpyridine triplet emission also suggests the
      population of a low-lying triplet state of the pyrene unit.

PMID- 22412329
TI  - Evaluation of cholinesterase activities during in vivo intoxication using an
      electrochemical sensor strip - correlation with intoxication symptoms.
AB  - Cholinesterase activity in blood of laboratory rats was monitored. Rats were
      intoxicated with paraoxon at dosis of 0 - 65 - 125 - 170 - 250 - 500 nmol. The
      250 nmol dose was found to be the LD(50). An electrochemical sensor was found
      useful to provide information about cholinesterase activity. The decrease of
      cholinesterase activity was correlated to intoxication symptoms and mortality
      level. It was found that the symptoms of intoxication are not observed while at
      least 50% of cholinesterase activity in blood remains. The minimal cholinesterase
      activity essential to survival is around 10%, when compared with the initial
      state. No changes in levels of low moleculary weight antioxidants were observed.

PMID- 22412330
TI  - Metadata behind the Interoperability of Wireless Sensor Networks.
AB  - Wireless Sensor Networks (WSNs) produce changes of status that are frequent,
      dynamic and unpredictable, and cannot be represented using a linear cause-effect
      approach. Consequently, a new approach is needed to handle these changes in order
      to support dynamic interoperability. Our approach is to introduce the notion of
      context as an explicit representation of changes of a WSN status inferred from
      metadata elements, which in turn, leads towards a decision-making process about
      how to maintain dynamic interoperability. This paper describes the developed
      context model to represent and reason over different WSN status based on four
      types of contexts, which have been identified as sensing, node, network and
      organisational contexts. The reasoning has been addressed by developing
      contextualising and bridges rules. As a result, we were able to demonstrate how
      contextualising rules have been used to reason on changes of WSN status as a
      first step towards maintaining dynamic interoperability.

PMID- 22412331
TI  - Digitally programmable analogue circuits for sensor conditioning systems.
AB  - This work presents two current-mode integrated circuits designed for sensor
      signal preprocessing in embedded systems. The proposed circuits have been
      designed to provide good signal transfer and fulfill their function, while
      minimizing the load effects due to building complex conditioning architectures.
      The processing architecture based on the proposed building blocks can be
      reconfigured through digital programmability. Thus, sensor useful range can be
      expanded, changes in the sensor operation can be compensated for and furthermore,
      undesirable effects such as device mismatching and undesired physical magnitudes
      sensor sensibilities are reduced. The circuits were integrated using a 0.35 MUm
      standard CMOS process. Experimental measurements, load effects and a study of two
      different tuning strategies are presented. From these results, system performance
      is tested in an application which entails extending the linear range of a magneto
      resistive sensor. Circuit area, average power consumption and programmability
      features allow these circuits to be included in embedded sensing systems as a
      part of the analogue conditioning components.

PMID- 22412332
TI  - Optimal Design and Operation for a No-Moving-Parts-Valve (NMPV) Micro-Pump with a
      Diffuser Width of 500 MUm.
AB  - A no-moving-parts-valve (NMPV) with a diffuser width of D = 500 microns was
      investigated in this study by numerical simulations at Reynolds numbers, Re(D),
      ranging from 20 to 75, and expansion valve angles ranging from 30 degrees  <
      theta(1) < 57 degrees  and 110 degrees  < theta(2) < 120 degrees . The D(p),(i)
      value, 1.02 < D(p),(i) < 1.14, is larger within the proposed range of the
      expansion valve angles. A flow channel structure with a depth of 500 micron is
      manufactured using yellow light lithography in this study. From prior analyses
      and experiments, it is found that piezoelectric films work better at a buzz
      driving frequency of f < 30Hz and the best operating frequency is at a driving
      frequency of f = 10Hz because it produces the largest net flow. In addition, the
      expansion angles theta(1) = 30 degrees  and theta(2) = 120 degrees  are the best
      expansion angles because they produce the largest net flow. These related results
      are very helpful for the actual design of no-moving-parts-valve micro-pump.

PMID- 22412333
TI  - Vehicle based laser range finding in crops.
AB  - Laser rangefinders and laser scanners are widely used for industrial purposes and
      for remote sensing. In agriculture information about crop parameters like volume,
      height, and density can support the optimisation of production processes. In
      scientific papers the measurement of these parameters by low cost laser
      rangefinders with one echo has been presented for short ranges. Because the cross
      section area of the beam increases with the measuring range, it can be expected
      that laser rangefinders will have a reduced measuring accuracy in small sized
      crops and when measuring far distances. These problems are caused by target areas
      smaller than the beam and by the beam striking the edges of crop objects. Lab
      tests under defined conditions and a real field test were performed to assess the
      measuring properties under such difficult conditions of a chosen low cost sensor.
      Based on lab tests it was shown that the accuracy was reduced, but the successful
      use of the sensor under field conditions demonstrated the potential to meet the
      demands for agricultural applications, Insights resulting from investigations
      made in the paper contribute to facilitating the choice or the development of
      laser rangefinder sensors for vehicle based measurement of crop parameters for
      optimisation of production processes.

PMID- 22412334
TI  - A hybrid stochastic approach for self-location of wireless sensors in indoor
      environments.
AB  - Indoor location systems, especially those using wireless sensor networks, are
      used in many application areas. While the need for these systems is widely
      proven, there is a clear lack of accuracy. Many of the implemented applications
      have high errors in their location estimation because of the issues arising in
      the indoor environment. Two different approaches had been proposed using WLAN
      location systems: on the one hand, the so-called deductive methods take into
      account the physical properties of signal propagation. These systems require a
      propagation model, an environment map, and the position of the radio-stations. On
      the other hand, the so-called inductive methods require a previous training phase
      where the system learns the received signal strength (RSS) in each location. This
      phase can be very time consuming. This paper proposes a new stochastic approach
      which is based on a combination of deductive and inductive methods whereby
      wireless sensors could determine their positions using WLAN technology inside a
      floor of a building. Our goal is to reduce the training phase in an indoor
      environment, but, without an loss of precision. Finally, we compare the
      measurements taken using our proposed method in a real environment with the
      measurements taken by other developed systems. Comparisons between the proposed
      system and other hybrid methods are also provided.

PMID- 22412336
TI  - Performance Analysis of the SIFT Operator for Automatic Feature Extraction and
      Matching in Photogrammetric Applications.
AB  - In the photogrammetry field, interest in region detectors, which are widely used
      in Computer Vision, is quickly increasing due to the availability of new
      techniques. Images acquired by Mobile Mapping Technology, Oblique Photogrammetric
      Cameras or Unmanned Aerial Vehicles do not observe normal acquisition conditions.
      Feature extraction and matching techniques, which are traditionally used in
      photogrammetry, are usually inefficient for these applications as they are unable
      to provide reliable results under extreme geometrical conditions (convergent
      taking geometry, strong affine transformations, etc.) and for bad-textured
      images. A performance analysis of the SIFT technique in aerial and close-range
      photogrammetric applications is presented in this paper. The goal is to establish
      the suitability of the SIFT technique for automatic tie point extraction and
      approximate DSM (Digital Surface Model) generation. First, the performances of
      the SIFT operator have been compared with those provided by feature extraction
      and matching techniques used in photogrammetry. All these techniques have been
      implemented by the authors and validated on aerial and terrestrial images.
      Moreover, an auto-adaptive version of the SIFT operator has been developed, in
      order to improve the performances of the SIFT detector in relation to the texture
      of the images. The Auto-Adaptive SIFT operator (A(2) SIFT) has been validated on
      several aerial images, with particular attention to large scale aerial images
      acquired using mini-UAV systems.

PMID- 22412335
TI  - Nucleic Acid-based Detection of Bacterial Pathogens Using Integrated Microfluidic
      Platform Systems.
AB  - The advent of nucleic acid-based pathogen detection methods offers increased
      sensitivity and specificity over traditional microbiological techniques, driving
      the development of portable, integrated biosensors. The miniaturization and
      automation of integrated detection systems presents a significant advantage for
      rapid, portable field-based testing. In this review, we highlight current
      developments and directions in nucleic acid-based micro total analysis systems
      for the detection of bacterial pathogens. Recent progress in the miniaturization
      of microfluidic processing steps for cell capture, DNA extraction and
      purification, polymerase chain reaction, and product detection are detailed.
      Discussions include strategies and challenges for implementation of an integrated
      portable platform.

PMID- 22412337
TI  - Novel Oversampling Technique for Improving Signal-to-Quantization Noise Ratio on
      Accelerometer-Based Smart Jerk Sensors in CNC Applications.
AB  - Jerk monitoring, defined as the first derivative of acceleration, has become a
      major issue in computerized numeric controlled (CNC) machines. Several works
      highlight the necessity of measuring jerk in a reliable way for improving
      production processes. Nowadays, the computation of jerk is done by finite
      differences of the acceleration signal, computed at the Nyquist rate, which leads
      to low signal-to-quantization noise ratio (SQNR) during the estimation. The
      novelty of this work is the development of a smart sensor for jerk monitoring
      from a standard accelerometer, which has improved SQNR. The proposal is based on
      oversampling techniques that give a better estimation of jerk than that produced
      by a Nyquist-rate differentiator. Simulations and experimental results are
      presented to show the overall methodology performance.

PMID- 22412338
TI  - Design of a Sensor Based on Plastic Optical Fibre (POF) to Measure Fluid Flow and
      Turbidity.
AB  - Although many optical fibre applications are based on their capacity to transmit
      optical signals with low losses, it can also be desirable for the optical fibre
      to be strongly affected by a certain physical parameter in the environment. In
      this way, it can be used as a sensor for this parameter. There are many strong
      arguments for the use of POFs as sensors. In addition to being easy to handle and
      low cost, they demonstrate advantages common to all multimode optical fibres.
      These specifically include flexibility, small size, good electromagnetic
      compatibility behaviour, and in general, the possibility of measuring any
      phenomenon without physically interacting with it. In this paper, a sensor based
      on POF is designed and analysed with the aim of measuring the volume and
      turbidity of a low viscosity fluid, in this case water, as it passes through a
      pipe. A comparative study with a commercial sensor is provided to validate the
      proven flow measurement. Likewise, turbidity is measured using different colour
      dyes. Finally, this paper will present the most significant results and
      conclusions from all the tests which are carried out.

PMID- 22412339
TI  - A review of current methodologies for regional evapotranspiration estimation from
      remotely sensed data.
AB  - An overview of the commonly applied evapotranspiration (ET) models using remotely
      sensed data is given to provide insight into the estimation of ET on a regional
      scale from satellite data. Generally, these models vary greatly in inputs, main
      assumptions and accuracy of results, etc. Besides the generally used remotely
      sensed multi-spectral data from visible to thermal infrared bands, most remotely
      sensed ET models, from simplified equations models to the more complex physically
      based two-source energy balance models, must rely to a certain degree on ground
      based auxiliary measurements in order to derive the turbulent heat fluxes on a
      regional scale. We discuss the main inputs, assumptions, theories, advantages and
      drawbacks of each model. Moreover, approaches to the extrapolation of
      instantaneous ET to the daily values are also briefly presented. In the final
      part, both associated problems and future trends regarding these remotely sensed
      ET models were analyzed to objectively show the limitations and promising aspects
      of the estimation of regional ET based on remotely sensed data and ground-based
      measurements.

PMID- 22412340
TI  - Nonlinear Dynamics and Chaos of Microcantilever-Based TM-AFMs with Squeeze Film
      Damping Effects.
AB  - In Atomic force microscope (AFM) examination of a vibrating microcantilever, the
      nonlinear tip-sample interaction would greatly influence the dynamics of the
      cantilever. In this paper, the nonlinear dynamics and chaos of a tip-sample
      dynamic system being run in the tapping mode (TM) were investigated by
      considering the effects of hydrodynamic loading and squeeze film damping. The
      microcantilever was modeled as a spring-mass-damping system and the interaction
      between the tip and the sample was described by the Lennard-Jones (LJ) potential.
      The fundamental frequency and quality factor were calculated from the transient
      oscillations of the microcantilever vibrating in air. Numerical simulations were
      carried out to study the coupled nonlinear dynamic system using the bifurcation
      diagram, Poincare maps, largest Lyapunov exponent, phase portraits and time
      histories. Results indicated the occurrence of periodic and chaotic motions and
      provided a comprehensive understanding of the hydrodynamic loading of
      microcantilevers. It was demonstrated that the coupled dynamic system will
      experience complex nonlinear oscillation as the system parameters change and the
      effect of squeeze film damping is not negligible on the micro-scale.

PMID- 22412341
TI  - Sun tracking systems: a review.
AB  - The output power produced by high-concentration solar thermal and photovoltaic
      systems is directly related to the amount of solar energy acquired by the system,
      and it is therefore necessary to track the sun's position with a high degree of
      accuracy. Many systems have been proposed to facilitate this task over the past
      20 years. Accordingly, this paper commences by providing a high level overview of
      the sun tracking system field and then describes some of the more significant
      proposals for closed-loop and open-loop types of sun tracking systems.

PMID- 22412342
TI  - Polarised multiangular reflectance measurements using the finnish geodetic
      institute field goniospectrometer.
AB  - The design, operation, and properties of the Finnish Geodetic Institute Field
      Goniospectrometer (FIGIFIGO) are presented. FIGIFIGO is a portable instrument for
      the measurement of surface Bidirectional Reflectance Factor (BRF) for samples
      with diameters of 10 - 50 cm. A set of polarising optics enable the measurement
      of linearly polarised BRF over the full solar spectrum (350 - 2,500 nm). FIGIFIGO
      is designed mainly for field operation using sunlight, but operation in a
      laboratory environment is also possible. The acquired BRF have an accuracy of 1 -
      5% depending on wavelength, sample properties, and measurement conditions. The
      angles are registered at accuracies better than 2 degrees . During 2004 - 2008,
      FIGIFIGO has been used in the measurement of over 150 samples, all around
      northern Europe. The samples concentrate mostly on boreal forest understorey,
      snow, urban surfaces, and reflectance calibration surfaces.

PMID- 22412343
TI  - Dynamic hierarchical sleep scheduling for wireless ad-hoc sensor networks.
AB  - This paper presents two scheduling management schemes for wireless sensor
      networks, which manage the sensors by utilizing the hierarchical network
      structure and allocate network resources efficiently. A local criterion is used
      to simultaneously establish the sensing coverage and connectivity such that
      dynamic cluster-based sleep scheduling can be achieved. The proposed schemes are
      simulated and analyzed to abstract the network behaviors in a number of settings.
      The experimental results show that the proposed algorithms provide efficient
      network power control and can achieve high scalability in wireless sensor
      networks.

PMID- 22412344
TI  - A heterogeneous wireless identification network for the localization of animals
      based on stochastic movements.
AB  - The improvement in the transmission range in wireless applications without the
      use of batteries remains a significant challenge in identification applications.
      In this paper, we describe a heterogeneous wireless identification network mostly
      powered by kinetic energy, which allows the localization of animals in open
      environments. The system relies on radio communications and a global positioning
      system. It is made up of primary and secondary nodes. Secondary nodes are kinetic
      powered and take advantage of animal movements to activate the node and transmit
      a specific identifier, reducing the number of batteries of the system. Primary
      nodes are battery-powered and gather secondary-node transmitted information to
      provide it, along with position and time data, to a final base station in charge
      of the animal monitoring. The system allows tracking based on contextual
      information obtained from statistical data.

PMID- 22412345
TI  - Using reputation systems and non-deterministic routing to secure wireless sensor
      networks.
AB  - Security in wireless sensor networks is difficult to achieve because of the
      resource limitations of the sensor nodes. We propose a trust-based decision
      framework for wireless sensor networks coupled with a non-deterministic routing
      protocol. Both provide a mechanism to effectively detect and confine common
      attacks, and, unlike previous approaches, allow bad reputation feedback to the
      network. This approach has been extensively simulated, obtaining good results,
      even for unrealistically complex attack scenarios.

PMID- 22412346
TI  - Multi-objective differential evolution for automatic clustering with application
      to micro-array data analysis.
AB  - This paper applies the Differential Evolution (DE) algorithm to the task of
      automatic fuzzy clustering in a Multi-objective Optimization (MO) framework. It
      compares the performances of two multi-objective variants of DE over the fuzzy
      clustering problem, where two conflicting fuzzy validity indices are
      simultaneously optimized. The resultant Pareto optimal set of solutions from each
      algorithm consists of a number of non-dominated solutions, from which the user
      can choose the most promising ones according to the problem specifications. A
      real-coded representation of the search variables, accommodating variable number
      of cluster centers, is used for DE. The performances of the multi-objective DE
      variants have also been contrasted to that of two most well-known schemes of MO
      clustering, namely the Non Dominated Sorting Genetic Algorithm (NSGA II) and
      Multi-Objective Clustering with an unknown number of Clusters K (MOCK).
      Experimental results using six artificial and four real life datasets of varying
      range of complexities indicate that DE holds immense promise as a candidate
      algorithm for devising MO clustering schemes.

PMID- 22412347
TI  - Guided wave and damage detection in composite laminates using different fiber
      optic sensors.
AB  - Guided wave detection using different fiber optic sensors and their applications
      in damage detection for composite laminates were systematically investigated and
      compared in this paper. Two types of fiber optic sensors, namely fiber Bragg
      gratings (FBG) and Doppler effect-based fiber optic (FOD) sensors, were addressed
      and guided wave detection systems were constructed for both types. Guided waves
      generated by a piezoelectric transducer were propagated through a quasi-isotropic
      carbon fiber reinforced plastic (CFRP) laminate and acquired by these fiber optic
      sensors. Characteristics of these fiber optic sensors in ultrasonic guided wave
      detection were systematically compared. Results demonstrated that both the FBG
      and FOD sensors can be applied in guided wave and damage detection for the CFRP
      laminates. The signal-to-noise ratio (SNR) of guided wave signal captured by an
      FOD sensor is relatively high in comparison with that of the FBG sensor because
      of their different physical principles in ultrasonic detection. Further, the FOD
      sensor is sensitive to the damage-induced fundamental shear horizontal (SH(0))
      guided wave that, however, cannot be detected by using the FBG sensor, because
      the FOD sensor is omnidirectional in ultrasound detection and, in contrast, the
      FBG sensor is severely direction dependent.

PMID- 22412348
TI  - Role of the gut endoderm in relaying left-right patterning in mice.
AB  - Establishment of left-right (LR) asymmetry occurs after gastrulation commences
      and utilizes a conserved cascade of events. In the mouse, LR symmetry is broken
      at a midline structure, the node, and involves signal relay to the lateral plate,
      where it results in asymmetric organ morphogenesis. How information transmits
      from the node to the distantly situated lateral plate remains unclear. Noting
      that embryos lacking Sox17 exhibit defects in both gut endoderm formation and LR
      patterning, we investigated a potential connection between these two processes.
      We observed an endoderm-specific absence of the critical gap junction component,
      Connexin43 (Cx43), in Sox17 mutants. Iontophoretic dye injection experiments
      revealed planar gap junction coupling across the gut endoderm in wild-type but
      not Sox17 mutant embryos. They also revealed uncoupling of left and right sides
      of the gut endoderm in an isolated domain of gap junction intercellular
      communication at the midline, which in principle could function as a barrier to
      communication between the left and right sides of the embryo. The role for gap
      junction communication in LR patterning was confirmed by pharmacological
      inhibition, which molecularly recapitulated the mutant phenotype. Collectively,
      our data demonstrate that Cx43-mediated communication across gap junctions within
      the gut endoderm serves as a mechanism for information relay between node and
      lateral plate in a process that is critical for the establishment of LR asymmetry
      in mice.

PMID- 22412350
TI  - In E. coli, interrupting one death pathway leads you down another.

PMID- 22412349
TI  - USF binding sequences from the HS4 insulator element impose early replication
      timing on a vertebrate replicator.
AB  - The nuclear genomes of vertebrates show a highly organized program of DNA
      replication where GC-rich isochores are replicated early in S-phase, while AT
      rich isochores are late replicating. GC-rich regions are gene dense and are
      enriched for active transcription, suggesting a connection between gene
      regulation and replication timing. Insulator elements can organize independent
      domains of gene transcription and are suitable candidates for being key
      regulators of replication timing. We have tested the impact of inserting a strong
      replication origin flanked by the beta-globin HS4 insulator on the replication
      timing of naturally late replicating regions in two different avian cell types,
      DT40 (lymphoid) and 6C2 (erythroid). We find that the HS4 insulator has the
      capacity to impose a shift to earlier replication. This shift requires the
      presence of HS4 on both sides of the replication origin and results in an advance
      of replication timing of the target locus from the second half of S-phase to the
      first half when a transcribed gene is positioned nearby. Moreover, we find that
      the USF transcription factor binding site is the key cis-element inside the HS4
      insulator that controls replication timing. Taken together, our data identify a
      combination of cis-elements that might constitute the basic unit of multi
      replicon megabase-sized early domains of DNA replication.

PMID- 22412351
TI  - A fishy way to discuss multiple genes affecting the same trait.
AB  - Developing interactive ways to teach about concepts such as complementation can
      be difficult. This approach, supported by learning data, uses blind cavefish as
      an example.

PMID- 22412352
TI  - Two programmed cell death systems in Escherichia coli: an apoptotic-like death is
      inhibited by the mazEF-mediated death pathway.
AB  - In eukaryotes, the classical form of programmed cell death (PCD) is apoptosis,
      which has as its specific characteristics DNA fragmentation and membrane
      depolarization. In Escherichia coli a different PCD system has been reported. It
      is mediated by the toxin-antitoxin system module mazEF. The E. coli mazEF module
      is one of the most thoroughly studied toxin-antitoxin systems. mazF encodes a
      stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the
      lethal effect of MazF. mazEF-mediated cell death is a population phenomenon
      requiring the quorum-sensing pentapeptide NNWNN designated Extracellular Death
      Factor (EDF). mazEF is triggered by several stressful conditions, including
      severe damage to the DNA. Here, using confocal microscopy and FACS analysis, we
      show that under conditions of severe DNA damage, the triggered mazEF-mediated
      cell death pathway leads to the inhibition of a second cell death pathway. The
      latter is an apoptotic-like death (ALD); ALD is mediated by recA and lexA. The
      mazEF-mediated pathway reduces recA mRNA levels. Based on these results, we offer
      a molecular model for the maintenance of an altruistic characteristic in cell
      populations. In our model, the ALD pathway is inhibited by the altruistic EDF
      mazEF-mediated death pathway.

PMID- 22412353
TI  - Impact of Scotland's smoke-free legislation on pregnancy complications:
      retrospective cohort study.
AB  - BACKGROUND: Both active smoking and environmental tobacco smoke exposure are
      associated with pregnancy complications. In March 2006, Scotland implemented
      legislation prohibiting smoking in all wholly or partially enclosed public
      spaces. The aim of this study was to determine the impact of this legislation on
      preterm delivery and small for gestational age. METHODS AND FINDINGS: We
      conducted logistic regression analyses using national administrative pregnancy
      data covering the whole of Scotland. Of the two breakpoints tested, 1 January
      2006 produced a better fit than the date when the legislation came into force (26
      March 2006), suggesting an anticipatory effect. Among the 716,941 eligible women
      who conceived between August 1995 and February 2009 and subsequently delivered a
      live-born, singleton infant between 24 and 44 wk gestation, the prevalence of
      current smoking fell from 25.4% before legislation to 18.8% after legislation
      (p<0.001). Three months prior to the legislation, there were significant
      decreases in small for gestational age (-4.52%, 95% CI -8.28, -0.60, p = 0.024),
      overall preterm delivery (-11.72%, 95% CI -15.87, -7.35, p<0.001), and
      spontaneous preterm labour (-11.35%, 95% CI -17.20, -5.09, p = 0.001). In sub
      group analyses, significant reductions were observed among both current and never
      smokers. CONCLUSIONS: Reductions were observed in the risk of preterm delivery
      and small for gestational age 3 mo prior to the introduction of legislation,
      although the former reversed partially following the legislation. There is
      growing evidence of the potential for tobacco control legislation to have a
      positive impact on health.

PMID- 22412354
TI  - Injectable and oral contraceptive use and cancers of the breast, cervix, ovary,
      and endometrium in black South African women: case-control study.
AB  - BACKGROUND: Oral contraceptives are known to influence the risk of cancers of the
      female reproductive system. Evidence regarding the relationship between
      injectable contraceptives and these cancers is limited, especially in black South
      Africans, among whom injectable contraceptives are used more commonly than oral
      contraceptives. METHODS AND FINDINGS: We analysed data from a South African
      hospital-based case-control study of black females aged 18-79 y, comparing self
      reported contraceptive use in patients with breast (n = 1,664), cervical (n =
      2,182), ovarian (n = 182), and endometrial (n = 182) cancer, with self-reported
      contraceptive use in 1,492 control patients diagnosed with cancers with no known
      relationship to hormonal contraceptive use. We adjusted for potential confounding
      factors, including age, calendar year of diagnosis, education, smoking, alcohol,
      parity/age at first birth, and number of sexual partners. Among controls, 26% had
      used injectable and 20% had used oral contraceptives. For current and more recent
      users versus never users of oral or injectable contraceptives, the odds ratios
      (ORs) for breast cancer were significantly increased in users of oral and/or
      injectable contraceptives (OR 1.66, 95% CI 1.28-2.16, p<0.001) and separately
      among those exclusively using oral (1.57, 1.03-2.40, p = 0.04) and exclusively
      using injectable (OR 1.83, 1.31-2.55, p<0.001) contraceptives; corresponding ORs
      for cervical cancer were 1.38 (1.08-1.77, p = 0.01), 1.01 (0.66-1.56, p = 0.96),
      and 1.58 (1.16-2.15, p = 0.004). There was no significant increase in breast or
      cervical cancer risk among women ceasing hormonal contraceptive use >=10 y
      previously (p = 0.3 and p = 0.9, respectively). For durations of use >=5 y versus
      never use, the ORs of ovarian cancer were 0.60 (0.36-0.99, p = 0.04) for oral
      and/or injectable contraceptive use and 0.07 (0.01-0.49, p = 0.008) for
      injectable use exclusively; corresponding ORs for endometrial cancer were 0.44
      (0.22-0.86, p = 0.02) and 0.36 (0.11-1.26, p = 0.1). CONCLUSIONS: In this study,
      use of oral and of injectable hormonal contraceptives was associated with a
      transiently increased risk of breast and cervical cancer and, for long durations
      of use, with a reduced risk of ovarian and endometrial cancer. The observed
      effects of injectable and of oral contraceptives on cancer risk in this study did
      not appear to differ substantially.

PMID- 22412355
TI  - Care seeking for neonatal illness in low- and middle-income countries: a
      systematic review.
AB  - BACKGROUND: Despite recent achievements to reduce child mortality, neonatal
      deaths continue to remain high, accounting for 41% of all deaths in children
      under five years of age worldwide, of which over 90% occur in low- and middle
      income countries (LMICs). Infections are a leading cause of death and limitations
      in care seeking for ill neonates contribute to high mortality rates. As estimates
      for care-seeking behaviors in LMICs have not been studied, this review describes
      care seeking for neonatal illnesses in LMICs, with particular attention to type
      of care sought. METHODS AND FINDINGS: We conducted a systematic literature review
      of studies that reported the proportion of caregivers that sought care for ill or
      suspected ill neonates in LMICs. The initial search yielded 784 studies, of which
      22 studies described relevant data from community household surveys, facility
      based surveys, and intervention trials. The majority of studies were from South
      Asia (n = 17/22), set in rural areas (n = 17/22), and published within the last 4
      years (n = 18/22). Of the 9,098 neonates who were ill or suspected to be ill,
      4,320 caregivers sought some type of care, including care from a health facility
      (n = 370) or provider (n = 1,813). Care seeking ranged between 10% and 100% among
      caregivers with a median of 59%. Care seeking from a health care provider yielded
      a similar range and median, while care seeking at a health care facility ranged
      between 1% and 100%, with a median of 20%. Care-seeking estimates were limited by
      the few studies conducted in urban settings and regions other than South Asia.
      There was a lack of consistency regarding illness, care-seeking, and care
      provider definitions. CONCLUSIONS: There is a paucity of data regarding newborn
      care-seeking behaviors; in South Asia, care seeking is low for newborn illness,
      especially in terms of care sought from health care facilities and medically
      trained providers. There is a need for representative data to describe care
      seeking patterns in different geographic regions and better understand mechanisms
      to enhance care seeking during this vulnerable time period.

PMID- 22412356
TI  - Guidance for evidence-informed policies about health systems: rationale for and
      challenges of guidance development.
AB  - In the first paper in a three-part series on health systems guidance, Xavier
      Bosch-Capblanch and colleagues examine how guidance is currently formulated in
      low- and middle-income countries, and the challenges to developing such guidance.

PMID- 22412358
TI  - State-space analysis of time-varying higher-order spike correlation for multiple
      neural spike train data.
AB  - Precise spike coordination between the spiking activities of multiple neurons is
      suggested as an indication of coordinated network activity in active cell
      assemblies. Spike correlation analysis aims to identify such cooperative network
      activity by detecting excess spike synchrony in simultaneously recorded multiple
      neural spike sequences. Cooperative activity is expected to organize dynamically
      during behavior and cognition; therefore currently available analysis techniques
      must be extended to enable the estimation of multiple time-varying spike
      interactions between neurons simultaneously. In particular, new methods must take
      advantage of the simultaneous observations of multiple neurons by addressing
      their higher-order dependencies, which cannot be revealed by pairwise analyses
      alone. In this paper, we develop a method for estimating time-varying spike
      interactions by means of a state-space analysis. Discretized parallel spike
      sequences are modeled as multi-variate binary processes using a log-linear model
      that provides a well-defined measure of higher-order spike correlation in an
      information geometry framework. We construct a recursive Bayesian filter/smoother
      for the extraction of spike interaction parameters. This method can
      simultaneously estimate the dynamic pairwise spike interactions of multiple
      single neurons, thereby extending the Ising/spin-glass model analysis of multiple
      neural spike train data to a nonstationary analysis. Furthermore, the method can
      estimate dynamic higher-order spike interactions. To validate the inclusion of
      the higher-order terms in the model, we construct an approximation method to
      assess the goodness-of-fit to spike data. In addition, we formulate a test method
      for the presence of higher-order spike correlation even in nonstationary spike
      data, e.g., data from awake behaving animals. The utility of the proposed methods
      is tested using simulated spike data with known underlying correlation dynamics.
      Finally, we apply the methods to neural spike data simultaneously recorded from
      the motor cortex of an awake monkey and demonstrate that the higher-order spike
      correlation organizes dynamically in relation to a behavioral demand.

PMID- 22412359
TI  - Epitope flexibility and dynamic footprint revealed by molecular dynamics of a
      pMHC-TCR complex.
AB  - The crystal structures of unliganded and liganded pMHC molecules provide a
      structural basis for TCR recognition yet they represent 'snapshots' and offer
      limited insight into dynamics that may be important for interaction and T cell
      activation. MHC molecules HLA-B*3501 and HLA-B*3508 both bind a 13 mer viral
      peptide (LPEP) yet only HLA-B*3508-LPEP induces a CTL response characterised by
      the dominant TCR clonetype SB27. HLA-B*3508-LPEP forms a tight and long-lived
      complex with SB27, but the relatively weak interaction between HLA-B*3501-LPEP
      and SB27 fails to trigger an immune response. HLA-B*3501 and HLA-B*3508 differ by
      only one amino acid (L/R156) located on alpha2-helix, but this does not alter the
      MHC or peptide structure nor does this polymorphic residue interact with the
      peptide or SB27. In the absence of a structural rationalisation for the
      differences in TCR engagement we performed a molecular dynamics study of both
      pMHC complexes and HLA-B*3508-LPEP in complex with SB27. This reveals that the
      high flexibility of the peptide in HLA-B*3501 compared to HLA-B*3508, which was
      not apparent in the crystal structure alone, may have an under-appreciated role
      in SB27 recognition. The TCR pivots atop peptide residues 6-9 and makes transient
      MHC contacts that extend those observed in the crystal structure. Thus MD offers
      an insight into 'scanning' mechanism of SB27 that extends the role of the
      germline encoded CDR2alpha and CDR2beta loops. Our data are consistent with the
      vast body of experimental observations for the pMHC-LPEP-SB27 interaction and
      provide additional insights not accessible using crystallography.

PMID- 22412360
TI  - Bonsai trees in your head: how the pavlovian system sculpts goal-directed choices
      by pruning decision trees.
AB  - When planning a series of actions, it is usually infeasible to consider all
      potential future sequences; instead, one must prune the decision tree. Provably
      optimal pruning is, however, still computationally ruinous and the specific
      approximations humans employ remain unknown. We designed a new sequential
      reinforcement-based task and showed that human subjects adopted a simple pruning
      strategy: during mental evaluation of a sequence of choices, they curtailed any
      further evaluation of a sequence as soon as they encountered a large loss. This
      pruning strategy was Pavlovian: it was reflexively evoked by large losses and
      persisted even when overwhelmingly counterproductive. It was also evident above
      and beyond loss aversion. We found that the tendency towards Pavlovian pruning
      was selectively predicted by the degree to which subjects exhibited sub-clinical
      mood disturbance, in accordance with theories that ascribe Pavlovian behavioural
      inhibition, via serotonin, a role in mood disorders. We conclude that Pavlovian
      behavioural inhibition shapes highly flexible, goal-directed choices in a manner
      that may be important for theories of decision-making in mood disorders.

PMID- 22412361
TI  - Inferring epidemic contact structure from phylogenetic trees.
AB  - Contact structure is believed to have a large impact on epidemic spreading and
      consequently using networks to model such contact structure continues to gain
      interest in epidemiology. However, detailed knowledge of the exact contact
      structure underlying real epidemics is limited. Here we address the question
      whether the structure of the contact network leaves a detectable genetic
      fingerprint in the pathogen population. To this end we compare phylogenies
      generated by disease outbreaks in simulated populations with different types of
      contact networks. We find that the shape of these phylogenies strongly depends on
      contact structure. In particular, measures of tree imbalance allow us to quantify
      to what extent the contact structure underlying an epidemic deviates from a null
      model contact network and illustrate this in the case of random mixing. Using a
      phylogeny from the Swiss HIV epidemic, we show that this epidemic has a
      significantly more unbalanced tree than would be expected from random mixing.

PMID- 22412362
TI  - Does sex speed up evolutionary rate and increase biodiversity?
AB  - Most empirical and theoretical studies have shown that sex increases the rate of
      evolution, although evidence of sex constraining genomic and epigenetic variation
      and slowing down evolution also exists. Faster rates with sex have been
      attributed to new gene combinations, removal of deleterious mutations, and
      adaptation to heterogeneous environments. Slower rates with sex have been
      attributed to removal of major genetic rearrangements, the cost of finding a
      mate, vulnerability to predation, and exposure to sexually transmitted diseases.
      Whether sex speeds or slows evolution, the connection between reproductive mode,
      the evolutionary rate, and species diversity remains largely unexplored. Here we
      present a spatially explicit model of ecological and evolutionary dynamics based
      on DNA sequence change to study the connection between mutation, speciation, and
      the resulting biodiversity in sexual and asexual populations. We show that faster
      speciation can decrease the abundance of newly formed species and thus decrease
      long-term biodiversity. In this way, sex can reduce diversity relative to asexual
      populations, because it leads to a higher rate of production of new species, but
      with lower abundances. Our results show that reproductive mode and the mechanisms
      underlying it can alter the link between mutation, evolutionary rate, speciation
      and biodiversity and we suggest that a high rate of evolution may not be required
      to yield high biodiversity.

PMID- 22412363
TI  - Mitochondrial variability as a source of extrinsic cellular noise.
AB  - We present a study investigating the role of mitochondrial variability in
      generating noise in eukaryotic cells. Noise in cellular physiology plays an
      important role in many fundamental cellular processes, including transcription,
      translation, stem cell differentiation and response to medication, but the
      specific random influences that affect these processes have yet to be clearly
      elucidated. Here we present a mechanism by which variability in mitochondrial
      volume and functionality, along with cell cycle dynamics, is linked to
      variability in transcription rate and hence has a profound effect on downstream
      cellular processes. Our model mechanism is supported by an appreciable volume of
      recent experimental evidence, and we present the results of several new
      experiments with which our model is also consistent. We find that noise due to
      mitochondrial variability can sometimes dominate over other extrinsic noise
      sources (such as cell cycle asynchronicity) and can significantly affect large
      scale observable properties such as cell cycle length and gene expression levels.
      We also explore two recent regulatory network-based models for stem cell
      differentiation, and find that extrinsic noise in transcription rate causes
      appreciable variability in the behaviour of these model systems. These results
      suggest that mitochondrial and transcriptional variability may be an important
      mechanism influencing a large variety of cellular processes and properties.

PMID- 22412364
TI  - Cytoskeletal signaling: is memory encoded in microtubule lattices by CaMKII
      phosphorylation?
AB  - Memory is attributed to strengthened synaptic connections among particular brain
      neurons, yet synaptic membrane components are transient, whereas memories can
      endure. This suggests synaptic information is encoded and 'hard-wired' elsewhere,
      e.g. at molecular levels within the post-synaptic neuron. In long-term
      potentiation (LTP), a cellular and molecular model for memory, post-synaptic
      calcium ion (Ca2+) flux activates the hexagonal Ca2+-calmodulin dependent kinase
      II (CaMKII), a dodacameric holoenzyme containing 2 hexagonal sets of 6 kinase
      domains. Each kinase domain can either phosphorylate substrate proteins, or not
      (i.e. encoding one bit). Thus each set of extended CaMKII kinases can potentially
      encode synaptic Ca2+ information via phosphorylation as ordered arrays of binary
      'bits'. Candidate sites for CaMKII phosphorylation-encoded molecular memory
      include microtubules (MTs), cylindrical organelles whose surfaces represent a
      regular lattice with a pattern of hexagonal polymers of the protein tubulin.
      Using molecular mechanics modeling and electrostatic profiling, we find that
      spatial dimensions and geometry of the extended CaMKII kinase domains precisely
      match those of MT hexagonal lattices. This suggests sets of six CaMKII kinase
      domains phosphorylate hexagonal MT lattice neighborhoods collectively, e.g.
      conveying synaptic information as ordered arrays of six "bits", and thus "bytes",
      with 64 to 5,281 possible bit states per CaMKII-MT byte. Signaling and encoding
      in MTs and other cytoskeletal structures offer rapid, robust solid-state
      information processing which may reflect a general code for MT-based memory and
      information processing within neurons and other eukaryotic cells.

PMID- 22412365
TI  - Ensemble models of neutrophil trafficking in severe sepsis.
AB  - A hallmark of severe sepsis is systemic inflammation which activates leukocytes
      and can result in their misdirection. This leads to both impaired migration to
      the locus of infection and increased infiltration into healthy tissues. In order
      to better understand the pathophysiologic mechanisms involved, we developed a
      coarse-grained phenomenological model of the acute inflammatory response in CLP
      (cecal ligation and puncture)-induced sepsis in rats. This model incorporates
      distinct neutrophil kinetic responses to the inflammatory stimulus and the
      dynamic interactions between components of a compartmentalized inflammatory
      response. Ensembles of model parameter sets consistent with experimental
      observations were statistically generated using a Markov-Chain Monte Carlo
      sampling. Prediction uncertainty in the model states was quantified over the
      resulting ensemble parameter sets. Forward simulation of the parameter ensembles
      successfully captured experimental features and predicted that systemically
      activated circulating neutrophils display impaired migration to the tissue and
      neutrophil sequestration in the lung, consequently contributing to tissue damage
      and mortality. Principal component and multiple regression analyses of the
      parameter ensembles estimated from survivor and non-survivor cohorts provide
      insight into pathologic mechanisms dictating outcome in sepsis. Furthermore, the
      model was extended to incorporate hypothetical mechanisms by which immune
      modulation using extracorporeal blood purification results in improved outcome in
      septic rats. Simulations identified a sub-population (about 18% of the treated
      population) that benefited from blood purification. Survivors displayed enhanced
      neutrophil migration to tissue and reduced sequestration of lung neutrophils,
      contributing to improved outcome. The model ensemble presented herein provides a
      platform for generating and testing hypotheses in silico, as well as motivating
      further experimental studies to advance understanding of the complex biological
      response to severe infection, a problem of growing magnitude in humans.

PMID- 22412366
TI  - Measured dynamic social contact patterns explain the spread of H1N1v influenza.
AB  - Patterns of social mixing are key determinants of epidemic spread. Here we
      present the results of an internet-based social contact survey completed by a
      cohort of participants over 9,000 times between July 2009 and March 2010, during
      the 2009 H1N1v influenza epidemic. We quantify the changes in social contact
      patterns over time, finding that school children make 40% fewer contacts during
      holiday periods than during term time. We use these dynamically varying contact
      patterns to parameterise an age-structured model of influenza spread, capturing
      well the observed patterns of incidence; the changing contact patterns resulted
      in a fall of approximately 35% in the reproduction number of influenza during the
      holidays. This work illustrates the importance of including changing mixing
      patterns in epidemic models. We conclude that changes in contact patterns explain
      changes in disease incidence, and that the timing of school terms drove the 2009
      H1N1v epidemic in the UK. Changes in social mixing patterns can be usefully
      measured through simple internet-based surveys.

PMID- 22412367
TI  - A common model for cytokine receptor activation: combined scissor-like rotation
      and self-rotation of receptor dimer induced by class I cytokine.
AB  - The precise mechanism by which the binding of a class I cytokine to the
      extracellular domain of its corresponding receptor transmits a signal through the
      cell membrane remains unclear. Receptor activation involves a cytokine-receptor
      complex with a 1?2 stoichiometry. Previously we used our transient-complex theory
      to calculate the rate constant of the initial cytokine-receptor binding to form a
      1?1 complex. Here we computed the binding pathway leading to the 1?2 activation
      complex. Three cytokine systems (growth hormone, erythropoietin, and prolactin)
      were studied, and the focus was on the binding of the extracellular domain of the
      second receptor molecule after forming the 1?1 complex. According to the
      transient-complex theory, translational and rotation diffusion of the binding
      entities bring them together to form a transient complex, which has near-native
      relative separation and orientation but not the short-range specific native
      interactions. Subsequently conformational rearrangement leads to the formation of
      the native complex. We found that the changes in relative orientations between
      the two receptor molecules from the transient complex to the 1?2 native complex
      are similar for the three cytokine-receptor systems. We thus propose a common
      model for receptor activation by class I cytokines, involving combined scissor
      like rotation and self-rotation of the two receptor molecules. Both types of
      rotations seem essential: the scissor-like rotation separates the intracellular
      domains of the two receptor molecules to make room for the associated Janus
      kinase molecules, while the self-rotation allows them to orient properly for
      transphosphorylation. This activation model explains a host of experimental
      observations. The transient-complex based approach presented here may provide a
      strategy for designing antagonists and prove useful for elucidating activation
      mechanisms of other receptors.

PMID- 22412368
TI  - Beyond the binding site: the role of the beta2-beta3 loop and extra-domain
      structures in PDZ domains.
AB  - A general paradigm to understand protein function is to look at properties of
      isolated well conserved domains, such as SH3 or PDZ domains. While common
      features of domain families are well understood, the role of subtle differences
      among members of these families is less clear. Here, molecular dynamics
      simulations indicate that the binding mechanism in PSD95-PDZ3 is critically
      regulated via interactions outside the canonical binding site, involving both the
      poorly conserved beta2-beta3 loop and an extra-domain helix. Using the CRIPT
      peptide as a prototypical ligand, our simulations suggest that a network of salt
      bridges between the ligand and this loop is necessary for binding. These contacts
      interconvert between each other on a time scale of a few tens of nanoseconds,
      making them elusive to X-ray crystallography. The loop is stabilized by an extra
      domain helix. The latter influences the global dynamics of the domain,
      considerably increasing binding affinity. We found that two key contacts between
      the helix and the domain, one involving the beta2-beta3 loop, provide an
      atomistic interpretation of the increased affinity. Our analysis indicates that
      both extra-domain segments and loosely conserved regions play critical roles in
      PDZ binding affinity and specificity.

PMID- 22412370
TI  - Taste for blood: hemoglobin as a nutrient source for pathogens.

PMID- 22412369
TI  - Whole genome deep sequencing of HIV-1 reveals the impact of early minor variants
      upon immune recognition during acute infection.
AB  - Deep sequencing technologies have the potential to transform the study of highly
      variable viral pathogens by providing a rapid and cost-effective approach to
      sensitively characterize rapidly evolving viral quasispecies. Here, we report on
      a high-throughput whole HIV-1 genome deep sequencing platform that combines 454
      pyrosequencing with novel assembly and variant detection algorithms. In one
      subject we combined these genetic data with detailed immunological analyses to
      comprehensively evaluate viral evolution and immune escape during the acute phase
      of HIV-1 infection. The majority of early, low frequency mutations represented
      viral adaptation to host CD8+ T cell responses, evidence of strong immune
      selection pressure occurring during the early decline from peak viremia. CD8+ T
      cell responses capable of recognizing these low frequency escape variants
      coincided with the selection and evolution of more effective secondary HLA-anchor
      escape mutations. Frequent, and in some cases rapid, reversion of transmitted
      mutations was also observed across the viral genome. When located within
      restricted CD8 epitopes these low frequency reverting mutations were sufficient
      to prime de novo responses to these epitopes, again illustrating the capacity of
      the immune response to recognize and respond to low frequency variants. More
      importantly, rapid viral escape from the most immunodominant CD8+ T cell
      responses coincided with plateauing of the initial viral load decline in this
      subject, suggestive of a potential link between maintenance of effective,
      dominant CD8 responses and the degree of early viremia reduction. We conclude
      that the early control of HIV-1 replication by immunodominant CD8+ T cell
      responses may be substantially influenced by rapid, low frequency viral
      adaptations not detected by conventional sequencing approaches, which warrants
      further investigation. These data support the critical need for vaccine-induced
      CD8+ T cell responses to target more highly constrained regions of the virus in
      order to ensure the maintenance of immunodominant CD8 responses and the sustained
      decline of early viremia.

PMID- 22412371
TI  - Differential function of lip residues in the mechanism and biology of an anthrax
      hemophore.
AB  - To replicate in mammalian hosts, bacterial pathogens must acquire iron. The
      majority of iron is coordinated to the protoporphyrin ring of heme, which is
      further bound to hemoglobin. Pathogenic bacteria utilize secreted hemophores to
      acquire heme from heme sources such as hemoglobin. Bacillus anthracis, the
      causative agent of anthrax disease, secretes two hemophores, IsdX1 and IsdX2, to
      acquire heme from host hemoglobin and enhance bacterial replication in iron
      starved environments. Both proteins contain NEAr-iron Transporter (NEAT) domains,
      a conserved protein module that functions in heme acquisition in Gram-positive
      pathogens. Here, we report the structure of IsdX1, the first of a Gram-positive
      hemophore, with and without bound heme. Overall, IsdX1 forms an immunoglobin-like
      fold that contains, similar to other NEAT proteins, a 3(10)-helix near the heme
      binding site. Because the mechanistic function of this helix in NEAT proteins is
      not yet defined, we focused on the contribution of this region to hemophore and
      NEAT protein activity, both biochemically and biologically in cultured cells.
      Site-directed mutagenesis of amino acids in and adjacent to the helix identified
      residues important for heme and hemoglobin association, with some mutations
      affecting both properties and other mutations affecting only heme stabilization.
      IsdX1 with mutations that reduced the ability to associate with hemoglobin and
      bind heme failed to restore the growth of a hemophore-deficient strain of B.
      anthracis on hemoglobin as the sole iron source. These data indicate that not
      only is the 3(10)-helix important for NEAT protein biology, but also that the
      processes of hemoglobin and heme binding can be both separate as well as coupled,
      the latter function being necessary for maximal heme-scavenging activity. These
      studies enhance our understanding of NEAT domain and hemophore function and set
      the stage for structure-based inhibitor design to block NEAT domain interaction
      with upstream ligands.

PMID- 22412372
TI  - Quantitative Proteomics of Intracellular Campylobacter jejuni Reveals Metabolic
      Reprogramming.
AB  - Campylobacter jejuni is the major cause of bacterial food-borne illness in the
      USA and Europe. An important virulence attribute of this bacterial pathogen is
      its ability to enter and survive within host cells. Here we show through a
      quantitative proteomic analysis that upon entry into host cells, C. jejuni
      undergoes a significant metabolic downshift. Furthermore, our results indicate
      that intracellular C. jejuni reprograms its respiration, favoring the respiration
      of fumarate. These results explain the poor ability of C. jejuni obtained from
      infected cells to grow under standard laboratory conditions and provide the bases
      for the development of novel anti microbial strategies that would target relevant
      metabolic pathways.

PMID- 22412373
TI  - Significant association of KIR2DL3-HLA-C1 combination with cerebral malaria and
      implications for co-evolution of KIR and HLA.
AB  - Cerebral malaria is a major, life-threatening complication of Plasmodium
      falciparum malaria, and has very high mortality rate. In murine malaria models,
      natural killer (NK) cell responses have been shown to play a crucial role in the
      pathogenesis of cerebral malaria. To investigate the role of NK cells in the
      developmental process of human cerebral malaria, we conducted a case-control
      study examining genotypes for killer immunoglobulin-like receptors (KIR) and
      their human leukocyte antigen (HLA) class I ligands in 477 malaria patients. We
      found that the combination of KIR2DL3 and its cognate HLA-C1 ligand was
      significantly associated with the development of cerebral malaria when compared
      with non-cerebral malaria (odds ratio 3.14, 95% confidence interval 1.52-6.48, P
      = 0.00079, corrected P = 0.02). In contrast, no other KIR-HLA pairs showed a
      significant association with cerebral malaria, suggesting that the NK cell
      repertoire shaped by the KIR2DL3-HLA-C1 interaction shows certain functional
      responses that facilitate development of cerebral malaria. Furthermore, the
      frequency of the KIR2DL3-HLA-C1 combination was found to be significantly lower
      in malaria high-endemic populations. These results suggest that natural selection
      has reduced the frequency of the KIR2DL3-HLA-C1 combination in malaria high
      endemic populations because of the propensity of interaction between KIR2DL3 and
      C1 to favor development of cerebral malaria. Our findings provide one possible
      explanation for KIR-HLA co-evolution driven by a microbial pathogen, and its
      effect on the global distribution of malaria, KIR and HLA.

PMID- 22412374
TI  - Influenza A virus infection of human primary dendritic cells impairs their
      ability to cross-present antigen to CD8 T cells.
AB  - Influenza A virus (IAV) infection is normally controlled by adaptive immune
      responses initiated by dendritic cells (DCs). We investigated the consequences of
      IAV infection of human primary DCs on their ability to function as antigen
      presenting cells. IAV was internalized by both myeloid DCs (mDCs) and
      plasmacytoid DCs but only mDCs supported viral replication. Although infected
      mDCs efficiently presented endogenous IAV antigens on MHC class II, this was not
      the case for presentation on MHC class I. Indeed, cross-presentation by
      uninfected cells of minute amounts of endocytosed, exogenous IAV was -300-fold
      more efficient than presentation of IAV antigens synthesized by infected cells
      and resulted in a statistically significant increase in expansion of IAV-specific
      CD8 T cells. Furthermore, IAV infection also impaired cross-presentation of other
      exogenous antigens, indicating that IAV infection broadly attenuates presentation
      on MHC class I molecules. Our results suggest that cross-presentation by
      uninfected mDCs is a preferred mechanism of antigen-presentation for the
      activation and expansion of CD8 T cells during IAV infection.

PMID- 22412375
TI  - Capsule type of Streptococcus pneumoniae determines growth phenotype.
AB  - The polysaccharide capsule of Streptococcus pneumoniae defines over ninety
      serotypes, which differ in their carriage prevalence and invasiveness for poorly
      understood reasons. Recently, an inverse correlation between carriage prevalence
      and oligosaccharide structure of a given capsule has been described. Our previous
      work suggested a link between serotype and growth in vitro. Here we investigate
      whether capsule production interferes with growth in vitro and whether this
      predicts carriage prevalence in vivo. Eighty-one capsule switch mutants were
      constructed representing nine different serotypes, five of low (4, 7F, 14, 15,
      18C) and four of high carriage prevalence (6B, 9V, 19F, 23F). Growth (length of
      lag phase, maximum optical density) of wildtype strains, nontypeable mutants and
      capsule switch mutants was studied in nutrient-restricted Lacks medium (MLM) and
      in rich undefined brain heart infusion broth supplemented with 5% foetal calf
      serum (BHI+FCS). In MLM growth phenotype depended on, and was transferred with,
      capsule operon type. Colonization efficiency of mouse nasopharynx also depended
      on, and was transferred with, capsule operon type. Capsule production interfered
      with growth, which correlated inversely with serotype-specific carriage
      prevalence. Serotypes with better growth and higher carriage prevalence produced
      thicker capsules (by electron microscopy, FITC-dextran exclusion assays and HPLC)
      than serotypes with delayed growth and low carriage prevalence. However,
      expression of cpsA, the first capsule gene, (by quantitative RT-PCR) correlated
      inversely with capsule thickness. Energy spent for capsule production
      (incorporation of H3-glucose) relative to amount of capsule produced was higher
      for serotypes with low carriage prevalence. Experiments in BHI+FCS showed overall
      better bacterial growth and more capsule production than growth in MLM and
      differences between serotypes were no longer apparent. Production of
      polysaccharide capsule in S. pneumoniae interferes with growth in nutrient
      limiting conditions probably by competition for energy against the central
      metabolism. Serotype-specific nasopharyngeal carriage prevalence in vivo is
      predicted by the growth phenotype.

PMID- 22412376
TI  - Metabolism of phosphatidylinositol 4-kinase IIIalpha-dependent PI4P Is subverted
      by HCV and is targeted by a 4-anilino quinazoline with antiviral activity.
AB  - 4-anilino quinazolines have been identified as inhibitors of HCV replication. The
      target of this class of compounds was proposed to be the viral protein NS5A,
      although unequivocal proof has never been presented. A 4-anilino quinazoline
      moiety is often found in kinase inhibitors, leading us to formulate the
      hypothesis that the anti-HCV activity displayed by these compounds might be due
      to inhibition of a cellular kinase. Type III phosphatidylinositol 4-kinase alpha
      (PI4KIIIalpha) has recently been identified as a host factor for HCV replication.
      We therefore evaluated AL-9, a compound prototypical of the 4-anilino quinazoline
      class, on selected phosphatidylinositol kinases. AL-9 inhibited purified
      PI4KIIIalpha and, to a lesser extent, PI4KIIIbeta. In Huh7.5 cells, PI4KIIIalpha
      is responsible for the phosphatidylinositol-4 phosphate (PI4P) pool present in
      the plasma membrane. Accordingly, we observed a gradual decrease of PI4P in the
      plasma membrane upon incubation with AL-9, indicating that this agent inhibits
      PI4KIIIalpha also in living cells. Conversely, AL-9 did not affect the level of
      PI4P in the Golgi membrane, suggesting that the PI4KIIIbeta isoform was not
      significantly inhibited under our experimental conditions. Incubation of cells
      expressing HCV proteins with AL-9 induced abnormally large clusters of NS5A, a
      phenomenon previously observed upon silencing PI4KIIIalpha by RNA interference.
      In light of our findings, we propose that the antiviral effect of 4-anilino
      quinazoline compounds is mediated by the inhibition of PI4KIIIalpha and the
      consequent depletion of PI4P required for the HCV membranous web. In addition, we
      noted that HCV has a profound effect on cellular PI4P distribution, causing
      significant enrichment of PI4P in the HCV-membranous web and a concomitant
      depletion of PI4P in the plasma membrane. This observation implies that HCV--by
      recruiting PI4KIIIalpha in the RNA replication complex--hijacks PI4P metabolism,
      ultimately resulting in a markedly altered subcellular distribution of the
      PI4KIIIalpha product.

PMID- 22412377
TI  - Human cytomegalovirus clinical strain-specific microRNA miR-UL148D targets the
      human chemokine RANTES during infection.
AB  - The human cytomegalovirus (HCMV) clinical strain Toledo and the attenuated strain
      AD169 exhibit a striking difference in pathogenic potential and cell tropism. The
      virulent Toledo genome contains a 15-kb segment, which is present in all virulent
      strains but is absent from the AD169 genome. The pathogenic differences between
      the 2 strains are thought to be associated with this additional genome segment.
      Cytokines induced during viral infection play major roles in the regulation of
      the cellular interactions involving cells of the immune and inflammatory systems
      and consequently determine the pathogenic outcome of infection. The chemokine
      RANTES (Regulated on activation, normal T-cell expressed and secreted) attracts
      immune cells during inflammation and the immune response, indicating a role for
      RANTES in viral pathogenesis. Here, we show that RANTES was downregulated in
      human foreskin fibroblast (HFF) cells at a later stage after infection with the
      Toledo strain but not after infection with the AD169 strain. miR-UL148D, the only
      miRNA predicted from the UL/b' sequences of the Toledo genome, targeted the 3'
      untranslated region of RANTES and induced degradation of RANTES mRNA during
      infection. While wild-type Toledo inhibited expression of RANTES in HFF cells,
      Toledo mutant virus in which miR-UL148D is specifically abrogated did not repress
      RANTES expression. Furthermore, miR-UL148D-mediated downregulation of RANTES was
      inhibited by treatment with a miR-UL148D-specific inhibitor designed to bind to
      the miR-UL148D sequence via an antisense mechanism, supporting the potential
      value of antisense agents as therapeutic tools directed against HCMV. Our
      findings identify a viral microRNA as a novel negative regulator of the chemokine
      RANTES and provide clues for understanding the pathogenesis of the clinical
      strains of HCMV.

PMID- 22412378
TI  - Precocious metamorphosis in the juvenile hormone-deficient mutant of the
      silkworm, Bombyx mori.
AB  - Insect molting and metamorphosis are intricately governed by two hormones,
      ecdysteroids and juvenile hormones (JHs). JHs prevent precocious metamorphosis
      and allow the larva to undergo multiple rounds of molting until it attains the
      proper size for metamorphosis. In the silkworm, Bombyx mori, several "moltinism"
      mutations have been identified that exhibit variations in the number of larval
      molts; however, none of them have been characterized molecularly. Here we report
      the identification and characterization of the gene responsible for the dimolting
      (mod) mutant that undergoes precocious metamorphosis with fewer larval-larval
      molts. We show that the mod mutation results in complete loss of JHs in the
      larval hemolymph and that the mutant phenotype can be rescued by topical
      application of a JH analog. We performed positional cloning of mod and found a
      null mutation in the cytochrome P450 gene CYP15C1 in the mod allele. We also
      demonstrated that CYP15C1 is specifically expressed in the corpus allatum, an
      endocrine organ that synthesizes and secretes JHs. Furthermore, a biochemical
      experiment showed that CYP15C1 epoxidizes farnesoic acid to JH acid in a highly
      stereospecific manner. Precocious metamorphosis of mod larvae was rescued when
      the wild-type allele of CYP15C1 was expressed in transgenic mod larvae using the
      GAL4/UAS system. Our data therefore reveal that CYP15C1 is the gene responsible
      for the mod mutation and is essential for JH biosynthesis. Remarkably, precocious
      larval-pupal transition in mod larvae does not occur in the first or second
      instar, suggesting that authentic epoxidized JHs are not essential in very young
      larvae of B. mori. Our identification of a JH-deficient mutant in this model
      insect will lead to a greater understanding of the molecular basis of the
      hormonal control of development and metamorphosis.

PMID- 22412379
TI  - Three essential ribonucleases-RNase Y, J1, and III-control the abundance of a
      majority of Bacillus subtilis mRNAs.
AB  - Bacillus subtilis possesses three essential enzymes thought to be involved in
      mRNA decay to varying degrees, namely RNase Y, RNase J1, and RNase III. Using
      recently developed high-resolution tiling arrays, we examined the effect of
      depletion of each of these enzymes on RNA abundance over the whole genome. The
      data are consistent with a model in which the degradation of a significant number
      of transcripts is dependent on endonucleolytic cleavage by RNase Y, followed by
      degradation of the downstream fragment by the 5'-3' exoribonuclease RNase J1.
      However, many full-size transcripts also accumulate under conditions of RNase J1
      insufficiency, compatible with a model whereby RNase J1 degrades transcripts
      either directly from the 5' end or very close to it. Although the abundance of a
      large number of transcripts was altered by depletion of RNase III, this appears
      to result primarily from indirect transcriptional effects. Lastly, RNase
      depletion led to the stabilization of many low-abundance potential regulatory
      RNAs, both in intergenic regions and in the antisense orientation to known
      transcripts.

PMID- 22412380
TI  - A natural system of chromosome transfer in Yersinia pseudotuberculosis.
AB  - The High Pathogenicity Island of Yersinia pseudotuberculosis IP32637 was
      previously shown to be horizontally transferable as part of a large chromosomal
      segment. We demonstrate here that at low temperature other chromosomal loci, as
      well as a non-mobilizable plasmid (pUC4K), are also transferable. This transfer,
      designated GDT4 (Generalized DNA Transfer at 4 degrees C), required the presence
      of an IP32637 endogenous plasmid (pGDT4) that carries several mobile genetic
      elements and a conjugation machinery. We established that cure of this plasmid or
      inactivation of its sex pilus fully abrogates this process. Analysis of the
      mobilized pUC4K recovered from transconjugants revealed the insertion of one of
      the pGDT4-borne ISs, designated ISYps1, at different sites on the transferred
      plasmid molecules. This IS belongs to the IS6 family, which moves by replicative
      transposition, and thus could drive the formation of cointegrates between pGDT4
      and the host chromosome and could mediate the transfer of chromosomal regions in
      an Hfr-like manner. In support of this model, we show that a suicide plasmid
      carrying ISYps1 is able to integrate itself, flanked by ISYps1 copies, at
      multiple locations into the Escherichia coli chromosome. Furthermore, we
      demonstrate the formation of RecA-independent cointegrates between the ISYps1
      harboring plasmid and an ISYps1-free replicon, leading to the passive transfer of
      the non-conjugative plasmid. We thus demonstrate here a natural mechanism of
      horizontal gene exchange, which is less constrained and more powerful than the
      classical Hfr mechanism, as it only requires the presence of an IS6-type element
      on a conjugative replicon to drive the horizontal transfer of any large block of
      plasmid or chromosomal DNA. This natural mechanism of chromosome transfer, which
      occurs under conditions mimicking those found in the environment, may thus play a
      significant role in bacterial evolution, pathogenesis, and adaptation to new
      ecological niches.

PMID- 22412381
TI  - A machine learning approach for identifying novel cell type-specific
      transcriptional regulators of myogenesis.
AB  - Transcriptional enhancers integrate the contributions of multiple classes of
      transcription factors (TFs) to orchestrate the myriad spatio-temporal gene
      expression programs that occur during development. A molecular understanding of
      enhancers with similar activities requires the identification of both their
      unique and their shared sequence features. To address this problem, we combined
      phylogenetic profiling with a DNA-based enhancer sequence classifier that
      analyzes the TF binding sites (TFBSs) governing the transcription of a co
      expressed gene set. We first assembled a small number of enhancers that are
      active in Drosophila melanogaster muscle founder cells (FCs) and other mesodermal
      cell types. Using phylogenetic profiling, we increased the number of enhancers by
      incorporating orthologous but divergent sequences from other Drosophila species.
      Functional assays revealed that the diverged enhancer orthologs were active in
      largely similar patterns as their D. melanogaster counterparts, although there
      was extensive evolutionary shuffling of known TFBSs. We then built and trained a
      classifier using this enhancer set and identified additional related enhancers
      based on the presence or absence of known and putative TFBSs. Predicted FC
      enhancers were over-represented in proximity to known FC genes; and many of the
      TFBSs learned by the classifier were found to be critical for enhancer activity,
      including POU homeodomain, Myb, Ets, Forkhead, and T-box motifs. Empirical
      testing also revealed that the T-box TF encoded by org-1 is a previously
      uncharacterized regulator of muscle cell identity. Finally, we found extensive
      diversity in the composition of TFBSs within known FC enhancers, suggesting that
      motif combinatorics plays an essential role in the cellular specificity exhibited
      by such enhancers. In summary, machine learning combined with evolutionary
      sequence analysis is useful for recognizing novel TFBSs and for facilitating the
      identification of cognate TFs that coordinate cell type-specific developmental
      gene expression patterns.

PMID- 22412382
TI  - The miR-35-41 family of microRNAs regulates RNAi sensitivity in Caenorhabditis
      elegans.
AB  - RNA interference (RNAi) utilizes small interfering RNAs (siRNAs) to direct
      silencing of specific genes through transcriptional and post-transcriptional
      mechanisms. The siRNA guides can originate from exogenous (exo-RNAi) or natural
      endogenous (endo-RNAi) sources of double-stranded RNA (dsRNA). In Caenorhabditis
      elegans, inactivation of genes that function in the endo-RNAi pathway can result
      in enhanced silencing of genes targeted by siRNAs from exogenous sources,
      indicating cross-regulation between the pathways. Here we show that members of
      another small RNA pathway, the mir-35-41 cluster of microRNAs (miRNAs) can
      regulate RNAi. In worms lacking miR-35-41, there is reduced expression of lin
      35/Rb, the C. elegans homolog of the tumor suppressor Retinoblastoma gene,
      previously shown to regulate RNAi responsiveness. Genome-wide microarray analyses
      show that targets of endo-siRNAs are up-regulated in mir-35-41 mutants, a
      phenotype also displayed by lin-35/Rb mutants. Furthermore, overexpression of lin
      35/Rb specifically rescues the RNAi hypersensitivity of mir-35-41 mutants.
      Although the mir-35-41 miRNAs appear to be exclusively expressed in germline and
      embryos, their effect on RNAi sensitivity is transmitted to multiple tissues and
      stages of development. Additionally, we demonstrate that maternal contribution of
      miR-35-41 or lin-35/Rb is sufficient to reduce RNAi effectiveness in progeny
      worms. Our results reveal that miRNAs can broadly regulate other small RNA
      pathways and, thus, have far reaching effects on gene expression beyond directly
      targeting specific mRNAs.

PMID- 22412383
TI  - Repression of germline RNAi pathways in somatic cells by retinoblastoma pathway
      chromatin complexes.
AB  - The retinoblastoma (Rb) tumor suppressor acts with a number of chromatin
      cofactors in a wide range of species to suppress cell proliferation. The
      Caenorhabditis elegans retinoblastoma gene and many of these cofactors, called
      synMuv B genes, were identified in genetic screens for cell lineage defects
      caused by growth factor misexpression. Mutations in many synMuv B genes,
      including lin-35/Rb, also cause somatic misexpression of the germline RNA
      processing P granules and enhanced RNAi. We show here that multiple small RNA
      components, including a set of germline-specific Argonaute genes, are
      misexpressed in the soma of many synMuv B mutant animals, revealing one node for
      enhanced RNAi. Distinct classes of synMuv B mutants differ in the subcellular
      architecture of their misexpressed P granules, their profile of misexpressed
      small RNA and P granule genes, as well as their enhancement of RNAi and the
      related silencing of transgenes. These differences define three classes of synMuv
      B genes, representing three chromatin complexes: a LIN-35/Rb-containing DRM core
      complex, a SUMO-recruited Mec complex, and a synMuv B heterochromatin complex,
      suggesting that intersecting chromatin pathways regulate the repression of small
      RNA and P granule genes in the soma and the potency of RNAi. Consistent with
      this, the DRM complex and the synMuv B heterochromatin complex were genetically
      additive and displayed distinct antagonistic interactions with the MES-4 histone
      methyltransferase and the MRG-1 chromodomain protein, two germline chromatin
      regulators required for the synMuv phenotype and the somatic misexpression of P
      granule components. Thus intersecting synMuv B chromatin pathways conspire with
      synMuv B suppressor chromatin factors to regulate the expression of small RNA
      pathway genes, which enables heightened RNAi response. Regulation of small RNA
      pathway genes by human retinoblastoma may also underlie its role as a tumor
      suppressor gene.

PMID- 22412384
TI  - Exploring the complexity of the HIV-1 fitness landscape.
AB  - Although fitness landscapes are central to evolutionary theory, so far no
      biologically realistic examples for large-scale fitness landscapes have been
      described. Most currently available biological examples are restricted to very
      few loci or alleles and therefore do not capture the high dimensionality
      characteristic of real fitness landscapes. Here we analyze large-scale fitness
      landscapes that are based on predictive models for in vitro replicative fitness
      of HIV-1. We find that these landscapes are characterized by large correlation
      lengths, considerable neutrality, and high ruggedness and that these properties
      depend only weakly on whether fitness is measured in the absence or presence of
      different antiretrovirals. Accordingly, adaptive processes on these landscapes
      depend sensitively on the initial conditions. While the relative extent to which
      mutations affect fitness on their own (main effects) or in combination with other
      mutations (epistasis) is a strong determinant of these properties, the fitness
      landscape of HIV-1 is considerably less rugged, less neutral, and more correlated
      than expected from the distribution of main effects and epistatic interactions
      alone. Overall this study confirms theoretical conjectures about the complexity
      of biological fitness landscapes and the importance of the high dimensionality of
      the genetic space in which adaptation takes place.

PMID- 22412385
TI  - The human pancreatic islet transcriptome: expression of candidate genes for type
      1 diabetes and the impact of pro-inflammatory cytokines.
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic beta cells are
      killed by infiltrating immune cells and by cytokines released by these cells.
      Signaling events occurring in the pancreatic beta cells are decisive for their
      survival or death in diabetes. We have used RNA sequencing (RNA-seq) to identify
      transcripts, including splice variants, expressed in human islets of Langerhans
      under control conditions or following exposure to the pro-inflammatory cytokines
      interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma). Based on this
      unique dataset, we examined whether putative candidate genes for T1D, previously
      identified by GWAS, are expressed in human islets. A total of 29,776 transcripts
      were identified as expressed in human islets. Expression of around 20% of these
      transcripts was modified by pro-inflammatory cytokines, including apoptosis- and
      inflammation-related genes. Chemokines were among the transcripts most modified
      by cytokines, a finding confirmed at the protein level by ELISA. Interestingly,
      35% of the genes expressed in human islets undergo alternative splicing as
      annotated in RefSeq, and cytokines caused substantial changes in spliced
      transcripts. Nova1, previously considered a brain-specific regulator of mRNA
      splicing, is expressed in islets and its knockdown modified splicing. 25/41 of
      the candidate genes for T1D are expressed in islets, and cytokines modified
      expression of several of these transcripts. The present study doubles the number
      of known genes expressed in human islets and shows that cytokines modify
      alternative splicing in human islet cells. Importantly, it indicates that more
      than half of the known T1D candidate genes are expressed in human islets. This,
      and the production of a large number of chemokines and cytokines by cytokine
      exposed islets, reinforces the concept of a dialog between pancreatic islets and
      the immune system in T1D. This dialog is modulated by candidate genes for the
      disease at both the immune system and beta cell level.

PMID- 22412386
TI  - Development of a panel of genome-wide ancestry informative markers to study
      admixture throughout the Americas.
AB  - Most individuals throughout the Americas are admixed descendants of Native
      American, European, and African ancestors. Complex historical factors have
      resulted in varying proportions of ancestral contributions between individuals
      within and among ethnic groups. We developed a panel of 446 ancestry informative
      markers (AIMs) optimized to estimate ancestral proportions in individuals and
      populations throughout Latin America. We used genome-wide data from 953
      individuals from diverse African, European, and Native American populations to
      select AIMs optimized for each of the three main continental populations that
      form the basis of modern Latin American populations. We selected markers on the
      basis of locus-specific branch length to be informative, well distributed
      throughout the genome, capable of being genotyped on widely available commercial
      platforms, and applicable throughout the Americas by minimizing within-continent
      heterogeneity. We then validated the panel in samples from four admixed
      populations by comparing ancestry estimates based on the AIMs panel to estimates
      based on genome-wide association study (GWAS) data. The panel provided balanced
      discriminatory power among the three ancestral populations and accurate estimates
      of individual ancestry proportions (R2 > 0.9 for ancestral components with
      significant between-subject variance). Finally, we genotyped samples from 18
      populations from Latin America using the AIMs panel and estimated variability in
      ancestry within and between these populations. This panel and its reference
      genotype information will be useful resources to explore population history of
      admixture in Latin America and to correct for the potential effects of population
      stratification in admixed samples in the region.

PMID- 22412387
TI  - Networks of neuronal genes affected by common and rare variants in autism
      spectrum disorders.
AB  - Autism spectrum disorders (ASD) are neurodevelopmental disorders with phenotypic
      and genetic heterogeneity. Recent studies have reported rare and de novo
      mutations in ASD, but the allelic architecture of ASD remains unclear. To assess
      the role of common and rare variations in ASD, we constructed a gene co
      expression network based on a widespread survey of gene expression in the human
      brain. We identified modules associated with specific cell types and processes.
      By integrating known rare mutations and the results of an ASD genome-wide
      association study (GWAS), we identified two neuronal modules that are perturbed
      by both rare and common variations. These modules contain highly connected genes
      that are involved in synaptic and neuronal plasticity and that are expressed in
      areas associated with learning and memory and sensory perception. The enrichment
      of common risk variants was replicated in two additional samples which include
      both simplex and multiplex families. An analysis of the combined contribution of
      common variants in the neuronal modules revealed a polygenic component to the
      risk of ASD. The results of this study point toward contribution of minor and
      major perturbations in the two sub-networks of neuronal genes to ASD risk.

PMID- 22412388
TI  - A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel
      susceptibility loci.
AB  - Crohn's disease (CD) is a complex disorder resulting from the interaction of
      intestinal microbiota with the host immune system in genetically susceptible
      individuals. The largest meta-analysis of genome-wide association to date
      identified 71 CD-susceptibility loci in individuals of European ancestry. An
      important epidemiological feature of CD is that it is 2-4 times more prevalent
      among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish
      Europeans (NJ). To explore genetic variation associated with CD in AJs, we
      conducted a genome-wide association study (GWAS) by combining raw genotype data
      across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery
      stage, followed up by a replication study in 971 cases and 2,124 controls. We
      confirmed genome-wide significant associations of 9 known CD loci in AJs and
      replicated 3 additional loci with strong signal (p<5*10-6). Novel signals
      detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p =
      2*10-8; combined odds ratio OR = 1.48), 2p15 (rs6545946, p = 7*10-9; OR = 1.16),
      8q21.11 (rs12677663, p = 2*10-8; OR = 1.15), 10q26.3 (rs10734105, p = 3*10-8; OR
      = 1.27), and 11q12.1 (rs11229030, p = 8*10-9; OR = 1.15), implicating
      biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3.
      In all, the 16 replicated and newly discovered loci, in addition to the three
      coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD
      risk in the AJ population. This study demonstrates the complementary value of
      genetic studies in the Ashkenazim.

PMID- 22412389
TI  - Error-prone ZW pairing and no evidence for meiotic sex chromosome inactivation in
      the chicken germ line.
AB  - In the male mouse the X and Y chromosomes pair and recombine within the small
      pseudoautosomal region. Genes located on the unsynapsed segments of the X and Y
      are transcriptionally silenced at pachytene by Meiotic Sex Chromosome
      Inactivation (MSCI). The degree to which MSCI is conserved in other vertebrates
      is currently unclear. In the female chicken the ZW bivalent is thought to undergo
      a transient phase of full synapsis at pachytene, starting from the homologous
      ends and spreading through the heterologous regions. It has been proposed that
      the repair of the ZW DNA double-strand breaks (DSBs) is postponed until diplotene
      and that the ZW bivalent is subject to MSCI, which is independent of its synaptic
      status. Here we present a distinct model of meiotic pairing and silencing of the
      ZW pair during chicken oogenesis. We show that, in most oocytes, DNA DSB foci on
      the ZW are resolved by the end of pachytene and that the ZW desynapses in broad
      synchrony with the autosomes. We unexpectedly find that ZW pairing is highly
      error prone, with many oocytes failing to engage in ZW synapsis and crossover
      formation. Oocytes with unsynapsed Z and W chromosomes nevertheless progress to
      the diplotene stage, suggesting that a checkpoint does not operate during
      pachytene in the chicken germ line. Using a combination of epigenetic profiling
      and RNA-FISH analysis, we find no evidence for MSCI, associated with neither the
      asynaptic ZW, as described in mammals, nor the synaptic ZW. The lack of
      conservation of MSCI in the chicken reopens the debate about the evolution of
      MSCI and its driving forces.

PMID- 22412390
TI  - Tcf7 is an important regulator of the switch of self-renewal and differentiation
      in a multipotential hematopoietic cell line.
AB  - A critical problem in biology is understanding how cells choose between self
      renewal and differentiation. To generate a comprehensive view of the mechanisms
      controlling early hematopoietic precursor self-renewal and differentiation, we
      used systems-based approaches and murine EML multipotential hematopoietic
      precursor cells as a primary model. EML cells give rise to a mixture of self
      renewing Lin-SCA+CD34+ cells and partially differentiated non-renewing Lin-SCA
      CD34- cells in a cell autonomous fashion. We identified and validated the HMG box
      protein TCF7 as a regulator in this self-renewal/differentiation switch that
      operates in the absence of autocrine Wnt signaling. We found that Tcf7 is the
      most down-regulated transcription factor when CD34+ cells switch into CD34-
      cells, using RNA-Seq. We subsequently identified the target genes bound by TCF7,
      using ChIP-Seq. We show that TCF7 and RUNX1 (AML1) bind to each other's promoter
      regions and that TCF7 is necessary for the production of the short isoforms, but
      not the long isoforms of RUNX1, suggesting that TCF7 and the short isoforms of
      RUNX1 function coordinately in regulation. Tcf7 knock-down experiments and Gene
      Set Enrichment Analyses suggest that TCF7 plays a dual role in promoting the
      expression of genes characteristic of self-renewing CD34+ cells while repressing
      genes activated in partially differentiated CD34- state. Finally a network of up
      regulated transcription factors of CD34+ cells was constructed. Factors that
      control hematopoietic stem cell (HSC) establishment and development, cell growth,
      and multipotency were identified. These studies in EML cells demonstrate
      fundamental cell-intrinsic properties of the switch between self-renewal and
      differentiation, and yield valuable insights for manipulating HSCs and other
      differentiating systems.

PMID- 22412391
TI  - Synthetic lethality of cohesins with PARPs and replication fork mediators.
AB  - Synthetic lethality has been proposed as a way to leverage the genetic
      differences found in tumor cells to affect their selective killing. Cohesins,
      which tether sister chromatids together until anaphase onset, are mutated in a
      variety of tumor types. The elucidation of synthetic lethal interactions with
      cohesin mutants therefore identifies potential therapeutic targets. We used a
      cross-species approach to identify robust negative genetic interactions with
      cohesin mutants. Utilizing essential and non-essential mutant synthetic genetic
      arrays in Saccharomyces cerevisiae, we screened genome-wide for genetic
      interactions with hypomorphic mutations in cohesin genes. A somatic cell
      proliferation assay in Caenorhabditis elegans demonstrated that the majority of
      interactions were conserved. Analysis of the interactions found that cohesin
      mutants require the function of genes that mediate replication fork progression.
      Conservation of these interactions between replication fork mediators and cohesin
      in both yeast and C. elegans prompted us to test whether other replication fork
      mediators not found in the yeast were required for viability in cohesin mutants.
      PARP1 has roles in the DNA damage response but also in the restart of stalled
      replication forks. We found that a hypomorphic allele of the C. elegans SMC1
      orthologue, him-1(e879), genetically interacted with mutations in the orthologues
      of PAR metabolism genes resulting in a reduced brood size and somatic cell
      defects. We then demonstrated that this interaction is conserved in human cells
      by showing that PARP inhibitors reduce the viability of cultured human cells
      depleted for cohesin components. This work demonstrates that large-scale genetic
      interaction screening in yeast can identify clinically relevant genetic
      interactions and suggests that PARP inhibitors, which are currently undergoing
      clinical trials as a treatment of homologous recombination-deficient cancers, may
      be effective in treating cancers that harbor cohesin mutations.

PMID- 22412394
TI  - Ti insertion in the MTe(5) (M = Zr, Hf) structure type: Hf(0.78)Ti(0.22)Te(5).
AB  - The group 5 mixed-metal telluride, Hf(0.78)Ti(0.22)Te(5) (hafnium titanium penta
      telluride), is isostructural with the binary phases HfTe(5) and ZrTe(5) and forms
      a layered structure extending parallel to (010). The layers are made up from
      chains of bicapped metal-centered trigonal prisms and zigzag Te chains. The metal
      site (site symmetry m2m) is occupied by statistically disordered Hf [78.1 (5)%]
      and Ti [21.9 (5)%]. In addition to the regular Te-Te pair [2.7448 (13) A] forming
      the short base of the equilateral triangle of the trigonal prism, an inter
      mediate Te?Te separation [2.9129 (9) A] is also found. The classical charge
      balance of the compound can be described as [M(4+)][Te(2-)][Te(2) (2-)][Te(2)
      (0)] (M = Hf, Ti). The individual metal content can vary in different crystals,
      apparently forming a random substitutional solid solution (Hf(1-x)Ti(x))Te(5),
      with 0.15 <= x <= 0.22.

PMID- 22412393
TI  - The silkworm coming of age--early.

PMID- 22412395
TI  - Didysprosium hepta-nickel.
AB  - The title compound, Dy(2)Ni(7), adopts the beta-Gd(2)Co(7)-type structure type.
      The asymmetric unit contains two Dy sites (both site symmetry 3m) and five Ni
      sites (site symmetries .m, .2/m and -3m, and two 3m). The four different Ni
      coordination polyhedra are Frank-Kasper icosa-hedra formed by five Dy and seven
      Ni atoms, four Dy and eight Ni, three Dy and nine Ni, and six Dy and six Ni
      atoms, respectively. The two different Dy coordination polyhedra are either
      pseudo Frank-Kasper icosa-hedra formed by two Dy and 18 Ni atoms or normal Frank
      Kasper icosa-hedra formed by four Dy and 12 Ni atoms.

PMID- 22412392
TI  - Spo0A~P imposes a temporal gate for the bimodal expression of competence in
      Bacillus subtilis.
AB  - ComK transcriptionally controls competence for the uptake of transforming DNA in
      Bacillus subtilis. Only 10%-20% of the cells in a clonal population are randomly
      selected for competence. Because ComK activates its own promoter, cells exceeding
      a threshold amount of ComK trigger a positive feedback loop, transitioning to the
      competence ON state. The transition rate increases to a maximum during the
      approach to stationary phase and then decreases, with most cells remaining OFF.
      The average basal rate of comK transcription increases transiently, defining a
      window of opportunity for transitions and accounting for the heterogeneity of
      competent populations. We show that as the concentration of the response
      regulator Spo0A~P increases during the entry to stationary phase it first induces
      comK promoter activity and then represses it by direct binding. Spo0A~P activates
      by antagonizing the repressor, Rok. This amplifies an inherent increase in basal
      level comK promoter activity that takes place during the approach to stationary
      phase and is a general feature of core promoters, serving to couple the
      probability of competence transitions to growth rate. Competence transitions are
      thus regulated by growth rate and temporally controlled by the complex mechanisms
      that govern the formation of Spo0A~P. On the level of individual cells, the fate
      determining noise for competence is intrinsic to the comK promoter. This overall
      mechanism has been stochastically simulated and shown to be plausible. Thus, a
      deterministic mechanism modulates an inherently stochastic process.

PMID- 22412396
TI  - LiCe(9)Mo(16)O(35).
AB  - The structure of lithium nona-cerium hexa-deca-molybdenum penta-trideca-oxide,
      LiCe(9)Mo(16)O(35), is isotypic with LiNd(9)Mo(16)O(35) [Gougeon Gall, Cuny,
      Gautier, Le Polles, Delevoye & Trebosc (2011 ?). Chem. Eur. J.17, 13806-13813].
      It is characterized by Mo(16)O(26) (i)O(10) (a) units (where i = inner and a =
      apical) containing Mo(16) clusters that share some of their O atoms to form
      infinite molybdenum cluster chains running parallel to the b axis and separated
      by Li(+) and Ce(3+) cations. The Mo(16) cluster units are centred at Wyckoff
      positions 2c and have point-group symmetry 2/m. The Li(+) atom, in a flattened
      octa-hedron of O atoms, is in a 2a Wyckoff position with 2/m symmetry. The Ce(3+)
      cations have coordination numbers to the O atoms of 6, 9 or 10. Two Ce, two Mo
      and five O atoms lie on sites with m symmetry (Wyckoff site 4i), and one Ce and
      one O atom on sites with 2/m symmetry (Wyckoff sites 2b and 2d, respectively).

PMID- 22412397
TI  - catena-Poly[[bis-(dimethyl-formamide-kappaO)cadmium]-bis-(MU-4-nitro-phenyl
      cyanamido-kappaN:N)].
AB  - In the title coordination polymer, [Cd(C(7)H(4)N(3)O(2))(2)(C(3)H(7)NO)(2)](n),
      the Cd(II) atom, lying on an inversion center, is six-coordinated in a distorted
      N(4)O(2) octa-hedral geometry. The N atoms of the 4-nitrophenylcyanamide anions
      form the equatorial plane and the O atoms of the dimethyl-formamide mol-ecules
      occupy the axial positions. The anions act as bridging ligands, connecting the Cd
      atoms into a one-dimensional coordination polymer along [100].

PMID- 22412398
TI  - Tris(2,2'-bipyridine-kappaN,N')cobalt(III) tris-(oxalato-kappaO,O)ferrate(III)
      mono-hydrate.
AB  - The title compound, [Co(C(10)H(8)N(2))(3)][Fe(C(2)O(4))(3)].H(2)O, con-sists of
      two discrete tris-(chelate) metal ions (Co(III)N(6) and Fe(III)O(6) chromophores)
      and a water mol-ecule. The structure is highly symmetrical; the Co(III) and
      Fe(III) ions occupy positions with site symmetry 3.2. The coordination polyhedra
      of the metal atoms have a nearly octa-hedral geometry with noticeable trigonal
      distortions. The Co-N and Fe-O bond lengths are equal by symmetry, viz. 1.981 (2)
      and 1.998 (4) A, respectively. The cations and anions are arranged alternately
      along their threefold rotation axes parallel to [001], forming chains that are
      packed in a hexa-gonal manner. The water mol-ecules occupy voids between the
      chains. The crystal under investigation was an inversion twin.

PMID- 22412399
TI  - Dichlorido[(1R,2R)-N-(pyridin-2-yl-methyl)cyclo-hexane-1,2-diamine
      kappaN,N',N'']mercury(II).
AB  - In the title compound, [HgCl(2)(C(12)H(19)N(3))], the Hg(II) ion is coordinated
      by three N atoms of the (1R,2R)-N-(pyridin-2-ylmeth-yl)cyclo-hexane-1,2-diamine
      ligand and by a Cl atom in the basal plane, and by a second Cl atom in the apical
      position, within a distorted square-pyramidal geometry. The coordination of the
      enanti-opure ligand to the metal atom renders the central N atom chiral with an S
      configuration, so the complex is enanti-omerically pure and corresponds to the
      S,R,R diastereoisomer. Mol-ecules are linked via weak N-H?Cl hydrogen bonds into
      a one-dimensional hydrogen-bonding supramolecular chain along the
      crystallographic b axis.

PMID- 22412400
TI  - cis-Dioxido[N'-(2-oxidobenzyl-idene)pyridinium-4-carbohydrazidato
      kappaO,N',O']vanadium(V).
AB  - The title Schiff base complex, [V(C(13)H(10)N(3)O(2))O(2)], features a square
      pyramidal coordination geometry defined by the O,N',O'-donors of the tridentate
      Schiff base ligand and two oxide O atoms; one oxide O atom occupies the apical
      position. In the crystal, pyridinium-oxide N-H?O hydrogen bonds lead to zigzag
      supra-molecular chains with a flattened topology along [101]. The investigated
      crystal was twinned by nonmerohedry; the minor component refined to 18.5 (5)%.

PMID- 22412401
TI  - catena-Poly[[(1,10-phenanthroline-kappaN,N')lead(II)]-di-MU-nitrato
      kappaO,O':O'';kappaO:O',O''-[(1,10-phenanthroline-kappaN,N')lead(II)]-bis-(MU
      2,2,2-trichloro-acetato-kappaO:O')].
AB  - In the title Pb(II) complex,
      [Pb(2)(C(2)Cl(3)O(2))(2)(NO(3))(2)(C(12)H(8)N(2))(2)](n), the 1,10-phenanthroline
      ligand is chelating, the nitrate anion chelates one Pb(II) ion and simultaneously
      bridges a neighbouring Pb(II) ion via the third O atom, and the trichloro-acetate
      anion is bidentate, bridging two Pb(II) ions. The coordination geometry is based
      on a penta-gonal-bipramidal geometry defined by an N(2)O(5) donor set with no
      obvious stereochemical role for the lead-bound lone pair of electrons. The
      coordination polymer has a zigzag topology along [010] and comprises alternating
      eight-membered {PbONO}(2) and {PbOCO}(2) rings.

PMID- 22412402
TI  - Bis[(2-chloro-4-fluoro-benz-yl)triphenyl-phospho-nium] bis-(1,2,5-thia-diazole
      3,4-dithiol-ato)nickelate(II).
AB  - The title ion-pair complex, (C(25)H(20)ClFP)(2)[Ni(C(2)N(2)S(3))(2)], was
      obtained by the direct reaction of (4-F,2-ClBzTPP)(+).Br(-) [4-F,2-ClBzTPP(+) is
      (2-chloro-4-fluoro-benz-yl)triphenyl-phos-pho-nium], NiCl(2).6H(2)O and Na(2)tdas
      (tdas(2-) is 1,2,5-thia-diazole-3,4-dithiol-ate) in methanol. The asymmetric unit
      of the title structure comprises one (4-F,2-ClBzTPP)(+) cation and half of an
      [Ni(tdas)(2)](2-) complex anion, with the Ni(II) ion situated on a center of
      symmetry, leading to a slightly distorted square-planar coordination of the
      latter. In the cation, the tetra-hedral angles around the P atom are nearly
      undistorted. In the crystal, the cations and anions are linked by C-H?S, C-H?N
      and C-H?Cl hydrogen bonds.

PMID- 22412403
TI  - Poly[[diaqua-(1,10-phenanthroline-kappaN,N')(MU(3)-4-sulfonato-benzene-1,2
      dicarboxyl-ato-kappaO:O,O:O)dysprosium(III)] dihydrate].
AB  - The 4-sulfophthalate trianion in the polymeric title complex,
      {[Dy(C(8)H(3)O(7)S)(C(12)H(8)N(2))(H(2)O)(2)].2H(2)O}(n), bridges three
      water/phenanthroline-coordinated Dy(III) atoms to form a three-dimensional
      network architecture. The metal atom is further chelated by a carboxyl-ate group
      and is covalently bonded to a monodentate carboxyl-ate group and to a monodentate
      sulfonate group in a distorted square-anti-prismatic geometry. The coordinating
      and the solvent water mol-ecules are hydrogen bonded to the network. In the
      crystal, one solvent water mol-ecule is disordered over two positions [major
      component = 59 (3)%].

PMID- 22412404
TI  - Di-MU-chlorido-bis-[(1,10-phenanthroline-kappaN,N')(trichloro-acetato
      kappaO)copper(II)].
AB  - The title compound, [Cu(2)(C(2)Cl(3)O(2))(2)Cl(2)(C(12)H(8)N(2))(2)], features a
      centrosymmetric binuclear complex. The coordination geometry around the Cu(II)
      atom is square-pyramidal, comprising two N atoms from a symmetrically chelating
      1,10-phenanthroline ligand, one O atom from a trichloro-acetate ligand and two
      Cl(-) anions. In addition, there is a weak intra-molecular Cu?O inter-action of
      2.9403 (14) A involving the carbonyl O atom of the trichloro-acetate ligand. The
      central Cu(2)Cl(2) core takes the form of a rhombus, owing to the disparate Cu-Cl
      bond lengths. Mol-ecules are connected in the crystal structure by C-H?Cl and C
      H?O inter-actions.

PMID- 22412405
TI  - (Dimethyl sulfoxide-kappaO)[2-({(ethyl-sulfan-yl)[2-(2-oxidobenzyl-idene
      kappaO)hydrazin-yl-idene-kappaN]meth-yl}-imino-meth-yl)-phenol-ato
      kappaO]dioxidouranium(VI).
AB  - The U(VI) atom in the title complex, [U(C(17)H(15)N(3)O(2)S)O(2)(C(2)H(6)OS)],
      exists within a distorted penta-gonal-pyramidal geometry where the oxide atoms
      occupy axial positions [O-U-O = 177.84 (14) degrees ] and the penta-gonal plane
      is defined by the N(2)O(2) atoms of the tetra-dentate Schiff base ligand and the
      O atom of the dimethyl sulfoxide mol-ecule. In the crystal, centrosymmetric
      aggregates are formed via pairs of C-H?O inter-actions. The azomethine C=N atoms
      and ethyl-thiolyl group are disordered over two orientations in a 0.828 (3):0.172
      (3) ratio.

PMID- 22412406
TI  - Dichlorido{1-[N-(5-chloro-2-oxidophen-yl)carboximido-yl]naphthalen-2-olato
      kappaO,N,O'}(methanol-kappaO)tin(IV).
AB  - In the title complex, [Sn(C(17)H(10)ClNO(2))Cl(2)(CH(3)OH)], the Sn(IV) atom
      features a distorted octa-hedral geometry defined by the O,N,O'-donors of the
      dianion, two Cl atoms and the methanol O atom. The six-membered chelate ring has
      a half-chair conformation with the Sn atom lying 0.449 (4) A out of the plane
      defined by the remaining atoms (r.m.s. deviation = 0.0238 A). Supra-molecular
      helical chains along [100], mediated by O-H?O hydrogen bonds, feature in the
      crystal packing. Chains are linked by C-H?O, C-H?Cl and pi-pi [centroid-centroid
      distance = 3.598 (2) A] inter-actions.

PMID- 22412407
TI  - {MU-2-[4-(1,3-Benzothia-zol-2-yl)phen-yl]-2-aza-propane-1,3-dithiol-ato
      kappaS,S':S,S'}bis-[tricarbonyl-iron(I)].
AB  - The title compound, [Fe(2)(C(15)H(12)N(2)S(3))(CO)(6)], was prepared as an aza
      dithiol-atodiiron model for the active site of [FeFe]-hydrogenase. The Fe(2)S(2)
      core adopts a butterfly shape, with each metal having a pseudo square-pyramidal
      geometry. The N-substituted aza-dithiol-ate is MU(2)-kappa(4)S,S':S,S'
      coordinated to the Fe(CO)(3) moieties to form two fused six-membered rings with
      different conformations. The sum of the C-N-C angles around the N atom [356.85
      (15) degrees ] indicates a flattening of the trigonal-pyramidal geometry about
      the N atom and an increase in the degree of sp(2)-hybridization.

PMID- 22412408
TI  - trans-Tetra-aqua-bis-(isonicotinamide-kappaN)cobalt(II) bis-(3-hy-droxy-benzoate)
      tetra-hydrate.
AB  - The asymmetric unit of the title compound,
      [Co(C(6)H(6)N(2)O)(2)(H(2)O)(4)](C(7)H(5)O(3))(2).4H(2)O, contains one-half of
      the complex cation with the Co(II) ion located on an inversion center, a 3-hy
      droxy-benzoate counter-anion and two uncoordinated water mol-ecules. Four water O
      atoms in the equatorial plane around the Co(II) ion [Co-O = 2.0593 (16) and
      2.1118 (16) A] form a slightly distorted square-planar arrangement, and the
      distorted octahedral geometry is completed by the two N atoms [Co-N = 2.1306 (18)
      A] from two isonicotinamide ligands. In the anion, the carboxyl-ate group is
      twisted from the attached benzene ring at 8.84 (17) degrees . In the crystal, a
      three-dimensional hydrogen-bonding network, formed by classical O-H?O and N-H?O
      hydrogen bonds, consolidates the crystal packing, which exhibits pi-pi inter
      actions between the benzene and pyridine rings, with centroid-centroid distances
      of 3.458 (1) and 3.606 (1) A, respectively.

PMID- 22412409
TI  - (Acetyl-acetonato-kappaO,O')(phthalo-cyaninato-kappaN)(phen-an-throline
      kappaN,N')erbium(III).
AB  - The title complex, [Er(C(32)H(16)N(8))(C(5)H(7)O(2))(C(12)H(8)N(2))], possesses a
      mirror plane and the asymmetric unit is half of the mol-ecule. The Er(III)
      cation, lying on the mirror plane, is eight-coordinated by two O atoms from
      acetyl-acetone, two N (N(phen)) atoms from 1,10-phenanthroline and four isoindole
      N (N(iso)) atoms from the phthalocyanine ligand in an anti-prismatic geometry.
      The Er-N distances are in the range 2.376 (5)-2.529 (4) A and the Er-O distance
      is 2.272 (3) A. Notably, the Er-N(iso) bonds are shorter than the Er-N(phen)
      bonds, but longer than the Er-O bonds.

PMID- 22412410
TI  - catena-Poly[[(triphenyl-phosphane-kappaP)copper(I)]-di-MU-bromido-[(triphenyl
      phos-phane-kappaP)copper(I)]-MU-1,3-bis(pyridin-4-yl)-propane-kappaN:N'].
AB  - Through a diffusion reaction, cuprous bromide, triphenyl-phosphane and 1,3-bis
      (pyridin-4-yl)propane (bpp) were self-assembled to form the one-dimensional title
      compound, [Cu(2)Br(2)(C(13)H(14)N(2))(C(18)H(15)P)(2)](n). Each Cu(I) atom is
      coordinated by two Br atoms, one P atom from a triphenyl-phosphane ligand and one
      N atom from a bpp mol-ecule in a distorted tetra-hedral geometry. Two MU(2)-Br
      bridges connect two [Cu(PPh(3))](+) units to form neutral [CuBr(PPh(3))](2)
      dimers, which are linked by the flexible bridging bpp ligands to form a one
      dimensional chain structure parallel to the c axis. The dihedral angle between
      the pyridine rings of the bpp ligand is 34.59 (14) degrees .

PMID- 22412411
TI  - Poly[bis-(MU-azido-kappaN:N)[MU-1,2-bis-(imid-azol-1-yl)ethane-kappaN:N]cadmium].
AB  - In the title three-dimensional coordination polymer,
      [Cd(N(3))(2)(C(8)H(10)N(4))](n), the coordination geometry around the Cd(II) atom
      is distorted octa-hedral. The Cd(II) atom is coordinated by two N atoms from two
      cis-positioned bridging 1,2-bis-(imidazol-1-yl)ethane (bime) ligands and four N
      atoms from four azide anions. Each azide ligand acts in an end-on bridging
      coordination mode. The azide ligands and Cd(II) atoms form a one-dimensional
      zigzag chain constructed from four-membered [Cd(N(3))(2)](n) metallacycles
      extending along the a axis. These inorganic chains are connected with four other
      chains via bridging bime ligands to form a three-dimensional coordination
      network.

PMID- 22412412
TI  - (Butan-2-ol-kappaO)[2-({(ethyl-sulfan-yl)[2-(2-oxidobenzyl-idene
      kappaO)hydrazinyl-idene-kappaN]meth-yl}imino-meth-yl)phenolato
      kappaO]dioxidouranium(VI).
AB  - The U atom in the title complex, [U(C(17)H(15)N(3)O(2)S)O(2)(C(4)H(10)O)], exists
      within a distorted penta-gonal-bipyramidal geometry where the oxide O atoms
      occupy axial positions [O-U-O = 179.61 (18) degrees ] and the penta-gonal plane
      is defined by the N(2)O(2) atoms of the tetra-dentate Schiff base ligand and the
      O atom of the butan-2-ol mol-ecule. In the crystal, centrosymmetric aggregates
      are formed via pairs of hy-droxy-phenoxide O-H?O hydrogen bonds. The azomethine
      C=N atoms, the ethyl-thiolyl group and the butyl group of the butan-2-ol mol
      ecule are disordered over two positions in a 0.668 (3):0.332 (3) ratio.

PMID- 22412414
TI  - (+)-Chlorido[(1,2,3,4-eta;kappaP)-2'-diphenyl-phosphanyl-2-diphenyl-phosphoryl
      1,1'-binaphth-yl]rhodium(I) methanol monosolvate.
AB  - In the title complex, [RhCl(C(44)H(32)OP(2))].CH(3)OH, the Rh(I) ion is
      coordinated by a naphthyl group of a partially oxidized 2,2'-bis-(diphenyl
      phosphan-yl)-1,1'-binaphthyl (BINAP) ligand in a eta(4) mode, one P atom of the
      diphenyl-phosphanyl group and one Cl atom. The P=O group does not inter-act with
      the Rh(I) ion but accepts an O-H?O hydrogen bond from the methanol solvent mol
      ecule.

PMID- 22412413
TI  - catena-Poly[[(MU-3-hy-droxy-benzoato-kappaO,O:O)(MU-3-hy-droxy-benzoato
      kappaO,O:O)(isonicotinamide-kappaN)-lead(II)] monohydrate].
AB  - In the crystal of the title polymeric compound,
      {[Pb(C(7)H(5)O(3))(2)(C(6)H(6)N(2)O)].H(2)O}(n), the Pb(II) ion is chelated by
      two carboxyl-ate groups of 3-hy-droxy-benzoate (HB) anions, and coordinated by
      one isonicotinamide mol-ecule; a carboxyl-ate O atom and a hy-droxy O atom from
      adjacent HB anions bridge the Pb(II) ion to form polymeric chains along [100], in
      which the Pb(II) ion is in an irregular seven-coordination geometry. The carboxyl
      ate groups of the HB ions are slightly twisted away from the attached benzene
      rings by 2.84 (15) and 4.8 (2) degrees . The planes of the two benzene rings of
      the HB ions are oriented with respect to each other at a dihedral angle of 84.41
      (8) degrees . In the crystal, adjacent polymeric chains inter-act via O-H?O, N
      H?O and weak C-H?O hydrogen bonds. The solvent water mol-ecule links with the
      polymeric chains via O-H?O hydrogen bonding. pi-pi stacking between the benzene
      and pyridine rings and between the benzene rings [centroid-centroid distances =
      3.731 (2) and 3.353 (2) A] are present in the crystal.

PMID- 22412415
TI  - Redetermination of catena-poly[[chlorido-(thio-urea-kappaS)copper(I)]-MU-thio
      urea-kappaS:S] at 100 K.
AB  - The structure of the polymeric title compound, [CuCl(CH(4)N(2)S)(2)](n), has been
      redetermined to modern standards of precision with anisotropic refinement and
      location of the H atoms. The previous structure report [Spofford & Amma (1970 ?).
      Acta Cryst. B26, 1474-1483] is generally confirmed to higher precision [typical
      Cu-S bond length s.u. values = 0.005 (old) and 0.001 A (new)]. The asymmetric
      unit contains two formula units, with both Cu(I) atoms coordinated by one
      terminal S atom and two bridging S atoms of thio-urea ligands. This connectivity
      leads to polymeric [100] chains in the crystal. If very long contacts to nearby
      chloride ions [2.8687 (9) and 3.1394 (12) A] are considered to be bonding, then
      very distorted CuS(3)Cl tetra-hedral coordination polyhedra arise. The crystal
      structure is consolidated by weak intra- and inter-chain N-H?S and N-H?Cl
      hydrogen bonds.

PMID- 22412416
TI  - catena-Poly[[bis-(1-methyl-1H-imidazole-kappaN)zinc]-MU-3-nitro-phthalato
      kappaO:O].
AB  - In the title complex, [Zn(C(8)H(3)NO(6))(C(4)H(6)N(2))(2)](n), the carboxyl-ate
      groups of the 3-nitro-phthalate dianion ligand coordinate the Zn(II) ion in a bis
      monodentate mode. The Zn(II) ion shows distorted tetra-hedral coordination as it
      is bonded to two O atoms from the carboxyl-ate groups of symmetry-related 3-nitro
      phthalate anions and two N atoms of two independent 1-methyl-imidazole mol
      ecules. The bridging 3-nitro-phthalate ligand allows the formation of one
      dimensional chains in the c direction. The crystal structure is further
      stabilized by weak inter-molecular C-H?O hydrogen bonds.

PMID- 22412417
TI  - Bis(MU-3-nitro-phthalato-kappaO:O)bis-[(thio-urea-kappaS)zinc] dihydrate.
AB  - In the title complex, [Zn(2)(C(8)H(3)NO(6))(2)(CH(4)N(2)S)(4)].2H(2)O, the
      carboxyl-ate groups of the 3-nitro-phthalate ligands coordinate in a bis
      monodentate mode to the Zn(II) cations. This results in the formation of a
      centrosymmetric dimer containing two Zn(II) cations with distorted tetra-hedral
      geometries provided by the O atoms of two different 3-nitro-phthalate dianions
      and the S atoms of two non-equivalent coordinated thio-urea mol-ecules. The
      crystal structure exhibits N-H?O and O-H?O hydrogen bonds which link the dimers
      into a three-dimensional network.

PMID- 22412418
TI  - (Picolinato-kappaN,O)[tris(2-isopropyl-1H-imidazol-4-yl
      kappaN)phosphane]cobalt(II) nitrate.
AB  - Single crystals of the title compound, [Co(C(6)H(4)NO(2))(C(18)H(27)N(6)P)]NO(3),
      were obtained from the reaction of nitrato[tris-(2-isopropyl-imidazol-4
      yl)phosphane]cobalt(II) nitrate with picolinic acid in the presence of potassium
      tert-butoxide as base. The coordination polyhedron around the central Co(II) ion
      is about halfway between square-pyramidal and trigonal-bipyramidal geometry. In
      the structure, the nitrate counter-anion is connected by N-H?O hydrogen bonding
      to the complex cation. Additionally, the complex cations form one-dimensional
      chains along [010] by hydrogen bonding of the NH group of an imidazole ring to
      the picolinate group of a neighbouring complex cation.

PMID- 22412419
TI  - catena-Poly[(diaqua-cadmium)-MU-4,4'-[sulfonyl-bis-(1,4-phenyl-ene-oxy)]-di-acet
      ato-kappaO,O':O'',O'''].
AB  - In the title coordination polymer, [Cd(C(16)H(12)O(8)S)(H(2)O)(2)](n), the Cd(II)
      ion is situated on a crystallographic twofold rotation axis, being coordinated by
      four O atoms from two bidentate 4,4'-[sulfonyl-bis-(1,4-phenyl-ene-oxy)]diacetate
      (L) ligands and two water mol-ecules in a highly distorted CdO(6) octa-hedral
      geometry. Each complete ligand L, which is also generated by twofold symmetry
      with the S atom lying on the rotation axis, bridges two Cd(II) atoms to form a
      polymeric zigzag chain propagating in the [10-1] direction. O-H?O hydrogen bonds
      between the coordinated water mol-ecules and carboxyl-ate O atoms are involved in
      the packing.

PMID- 22412420
TI  - MU-Benzene-1,2,4,5-tetra-carboxyl-ato-kappaO,O:O,O-bis-[diaqua(phen-an-thro-line
      kappaN,N')nickel(II)] 0.67-hydrate.
AB  - The asymmetric unit of the title compound,
      [Ni(2)(C(10)H(2)O(8))(C(12)H(8)N(2))(2)(H(2)O)(4)].0.67H(2)O, contains one
      complete binuclear complex and one half-mol-ecule, the latter being completed by
      crystallographic inversion symmetry, and 0.67 of a solvent water molecule. Each
      Ni(2+) cation is coordinated by a 1,10-phenanthroline ligand, a bidentate benzene
      1,2,4,5-tetra-carboxyl-ate (btec) tetra-anion and two water mol-ecules to
      generate a distorted cis-NiN(2)O(4) octa-hedral coordination geometry. The btec
      species bridges the metal ions. In the crystal, the clusters and uncoordinated
      water mol-ecules are linked by O-H?O hydrogen bonds and pi-pi inter-actions
      [shortest centroid-centroid separation = 3.596 (2) A] to form a three-dimensional
      network.

PMID- 22412421
TI  - cis-Dichloridobis[tris-(2-methyl-phen-oxy)phosphane-kappaP]palladium(II).
AB  - In the title compound, [PdCl(2)(C(21)H(21)O(3)P)(2)], the Pd atom adopts a
      slightly distorted square-planar coordination geometry, with pairs of the
      equivalent ligands in cis positions. Adjacent mol-ecules are linked by weak C
      H?Cl hydrogen bonds. The crystal structure is additionally stabilized by pi-pi
      stacking inter-actions between the aromatic rings [shortest centroid-centroid
      distance = 3.758 (4) A].

PMID- 22412422
TI  - MU(3)-Chlorido-tris-(bis-{1-[2-(dimethyl-amino)-eth-yl]-3-methyl-imidazol-2-yl
      idene}silver(I)) dichloride.
AB  - In the crystal structure of the title compound, [Ag(3)Cl(C(8)H(15)N(3))(6)]Cl(2),
      the Ag(I) ion, which is located on a twofold rotation axis, exists in a T-shape
      coordination environment. Two carbene C atoms of the N-heterocyclic carbene (NHC)
      ligands are bonded tightly forming a slightly bent [Ag(NHC)(2)](+) cation [C-Ag-C
      angle = 162.80 (18) degrees ]. Three of these complex cations are further
      aggregated by one bridging chloride anion, which is lying on a threefold
      rotoinversion axis and is only loosely binding to the Ag(+) ions. The N atom of
      the amine group is not engaged in any coordinative bond.

PMID- 22412423
TI  - Bis[N-(3-amino-prop-yl)propane-1,3-di-amine-kappaN,N',N'']cadmium nitrate
      perchlorate.
AB  - The title complex, [Cd(C(6)H(17)N(3))(2)](ClO(4))(NO(3)), was synthesized by the
      reaction of Cd(NO(3))(2).4H(2)O, bis-(3-amino-prop-yl)-amine and sodium
      perchlorate in methanol. The asymmetric unit of the title complex consists of one
      Cd(2+) cation, two tridentate bis-(3-amino-prop-yl)amine ligands, one nitrate
      anion and one perchlorate anion. The Cd(2+) cation is coordinated by six N atoms
      of the bis-(3-amino-prop-yl)amine ligands in a slightly distorted octa-hedral
      coordination geometry. In the crystal, mol-ecules are held together by an
      intricate network of N-H?O inter-actions. One of the two amine ligands was found
      to be disordered over two sets of sites, with a ratio of 0.802 (3):0.198 (3),
      similarly to the nitrate anion, with a ratio of 0.762 (10):0.238 (10).

PMID- 22412424
TI  - A second polymorph of aqua-{4-chloro-2-[(pyridin-2-ylmeth-yl)imino-meth-yl]
      phenolato}copper(II) nitrate mono-hydrate.
AB  - The title complex, [Cu(C(13)H(10)ClN(2)O)(H(2)O)]NO(3).H(2)O, was obtained by the
      reaction of 5-chloro-salicyl-aldehyde, 2-(amino-meth-yl)pyridine and copper
      nitrate in methanol. The first reported polymorph of this complex was triclinic
      [Liang et al. (2010 ?). Acta Cryst. E66, m40]. The present polymorph crystallized
      in the monoclinic space group P2(1)/c. The Cu(II) ion is in a square planar
      environment and is coordinated by one phenolate O, one imine N and one pyridine N
      atom of the tridentate Schiff base ligand and by one water O atom. In the
      crystal, mol-ecules are linked through inter-molecular O-H?O hydrogen bonds to
      form chains along the a axis.

PMID- 22412425
TI  - Bis[4-amino-N-(pyrimidin-2-yl-kappaN)benzene-sulfonamidato-kappaN](4,4'-di-methyl
      2,2'-bipyridine-kappaN,N')cadmium dimethyl-formamide disolvate.
AB  - In the title compound, [Cd(C(10)H(9)N(4)O(2)S)(2)(C(12)H(12)N(2))].2C(3)H(7)NO,
      the Cd(II) ion lies on a twofold rotation axis, is six-coordinated by N atoms,
      and displays a trigonal-prismatic geometry arising from the two sulfadiazinate
      ligands and one 4,4'-dimethyl-2,2'-bipyridine ligand. Both ligands are bidentate
      and coordinate via their N atoms. The O and carbonyl C atoms of the dimethyl
      formamide mol-ecule show disorder and were modelled with two different
      orientations and with site occupancies of 0.584 (10):0.416 (10). The geometry
      around the sulfadiazine S atom is distorted tetra-hedral. The crystal structure
      involves N-H?O hydrogen bonds which link mol-ecules into a three-dimensional
      network. Weak C-H?O hydrogen bonds are also observed.

PMID- 22412426
TI  - Bis{4-bromo-2-[(naphthalen-1-yl-imino)-meth-yl]phenolato-kappaN,O}copper(II).
AB  - The title complex, [Cu(C(17)H(11)BrNO)(2)], lies on a centre of inversion. The
      chelating Schiff base anions define a square-planar N(2)O(2) donor set. The
      nearly perpendicular orientation of the naphthyl residues of the chelate ring
      [dihedral angle = 82.12 (12) degrees ] precludes the Cu(II) centre from
      additional coordination. In the refinement, the naphthyl rings were found to be
      disordered over two positions.; the major component has a site occupancy of 0.667
      (4).

PMID- 22412427
TI  - {4-Bromo-2-[(2-{(ethyl-sulfan-yl)[(2-oxidobenzyl-idene-kappaO)amino
      kappaN]methylidene}hydrazinyl-idene-kappaN)meth-yl]phenolato-kappaO}(butan-2-ol
      kappaO)dioxidouranium(VI).
AB  - The U(VI) cation in the title complex,
      [U(C(17)H(14)BrN(3)O(2)S)O(2)(C(4)H(10)O)], exists within a distorted penta-gonal
      bipyramidal geometry, where the oxide atoms occupy the axial positions [O-U-O =
      179.8 (3) degrees ] and the penta-gonal plane is defined by the N(2)O(2) atoms of
      the tetra-dentate Schiff base ligand and the O atom of the 2-butanol mol-ecule.
      In the crystal, centrosymmetric aggregates are formed via pairs of hy-droxy
      phenolate O-H?O hydrogen bonds. The azomethine C=N atoms, the ethyl-thiolyl
      group, the 2-butanol mol-ecule and Br atom are disordered over two positions in a
      0.627 (3):0.373 (3) ratio.

PMID- 22412428
TI  - MU(3)-Bromido-oxidotri-MU(3)-sulfido-tris-(triphenyl-phosphane-kappaP)-tri
      copper(I)-tungsten(VI).
AB  - The title complex, [Cu(3)WBrOS(3)(C(18)H(15)P)(3)], a neutral heavily distorted
      cubane-like W/S/Cu cluster, was self-assembled from ammonium trithio
      tungstate(VI), cuprous bromide and triphenyl-phosphane in N,N-dimethyl-formamide.
      The average Cu-Br, Cu-S and W-MU(3)-S bond lengths are 2.731 (2), 2.318 (2) and
      2.256 (2) A, respectively, in the distorted cubane-like skeleton. The W atom
      exhibits tetra-hedral geometry, formed by one terminal O atom and three MU(3)-S
      atoms; the W-O bond length is 1.728 (6) A. Each Cu atom is coordinated by one P
      atom from a triphenyl-phosphane ligand, and two MU(3)-S and one MU(3)-Br atoms,
      forming a distorted tetra-hedral coordination geometry.

PMID- 22412429
TI  - {4,4'-Dibromo-6,6'-dimeth-oxy-2,2'-[1,2-phenyl-enebis(nitrilo-methanylyl-idene)]
      kappaO,N,N',O}nickel(II).
AB  - In the title complex, [Ni(C(22)H(16)Br(2)N(2)O(4))], the Ni(II) ion is
      coordinated by two N atoms and two O atoms of a tetra-dentate Schiff base ligand,
      forming a slightly distorted square-planar coordination environment. The dihedral
      angle between the two bromo-substituted benzene rings is 10.1 (3) degrees .

PMID- 22412430
TI  - catena-Poly[[(isoquinoline-kappaN)(triphenylphospane-kappaP)copper(I)]-MU-thio
      cyanato-kappaN:S].
AB  - In the title coordination compound, [Cu(NCS)(C(9)H(7)N)(C(18)H(15)P)](n), the
      Cu(I) atom is tetra-hedrally coordinated by one N atom from an isoquinoline
      ligand, one P atom from a triphenyl-phospane ligand, and one N and one S atom
      from two thio-cyanate anions. The thio-cyanide anions bridge the Cu(I) atoms into
      a chain along [100]. pi-pi inter-actions between the pyridine and benzene rings
      of the isoquinoline ligands connect the chains [centroid-to-centroid distance =
      3.722 (3) A].

PMID- 22412431
TI  - Bis(diisopropyl-ammonium) tetra-chloridocuprate(II).
AB  - In the title mol-ecular salt, (C(6)H(16)N)(2)[CuCl(4)], the Cu(II) ion adopts an
      extremely distorted tetra-hedral coordination geometry. All the ammonium H atoms
      are involved in N-H?Cl hydrogen bonds, which serve to link the cations and anions
      into chains propagating along the c-axis direction.

PMID- 22412432
TI  - Triaqua-chlorido(18-crown-6)barium chloride.
AB  - In the title compound, [BaCl(C(12)H(24)O(6))(H(2)O)(3)]Cl, the Ba(II) atom, the
      coordinating and free Cl(-) anions, one coordinating water mol-ecule and two O
      atoms of an 18-crown-6 mol-ecule lie on a mirror plane. The environment of the
      ten-coordinate Ba(2+) ion is defined by one Cl atom, three water mol-ecules and
      six O atoms from the macrocyclic ether. The macrocycle adopts a conformation with
      an approximate D(3d) symmetry. In the crystal, O-H?Cl hydrogen bonds link the
      complex cations and Cl(-) anions into a two-dimensional network parallel to
      (010). An intra-molecular O-H?Cl hydrogen bond is also present.

PMID- 22412433
TI  - Poly[[penta-aqua-(MU(4)-pyridine-2,4,6-tri-carboxyl-ato)(MU(3)-pyridine-2,4,6-tri
      carboxyl-ato)disamarium(III)] mono-hydrate].
AB  - The asymmetric unit of the title compound,
      {[Sm(2)(C(8)H(2)NO(6))(2)(H(2)O)(5)].H(2)O}(n), contains two independent Sm(III)
      ions, two pyridine-2,4,6-tricarboxyl-ate (ptc) ligands, five aqua ligands and one
      lattice water mol-ecule. One Sm(III) ion is nine-coordinated by one N and five O
      atoms from the three ptc ligands and three aqua ligands in a distorted monocapped
      square antiprismatic geometry, and the other is eight-coordinated by one N and
      five O atoms from three ptc ligands and two aqua ligands in a 4,4'-bicapped
      trigonal anti-prismatic geometry. The ptc ligands brigde the Sm(III) ions into a
      three-dimensional polymeric framework. Extensive O-H?O hydrogen bonding is
      observed in the crystal structure.

PMID- 22412434
TI  - Tetra-aqua-tetra-kis-(4,4'-bipyridine dioxide-kappaO)terbium(III) octa
      cyanidotungstate(V).
AB  - In the title compound, [Tb(C(10)H(8)N(2)O(2))(4)(H(2)O)(4)][W(CN)(8)], both metal
      atoms are eight-coordinated. The Tb(III) ion displays a dodeca-hedral geometry,
      while the W(v) ion exhibits a distorted square-anti-prismatic geometry. The Tb
      atoms are located on a special position of site symmetry -4, whereas the W atoms
      are located on a twofold rotation axis. The cations are linked by O-H?O hydrogen
      bonds. The title compound is isotypic with the corresponding and previously
      described Mo compound [Qian & Yuan (2011 ?). Acta Cryst. E67, m845].

PMID- 22412435
TI  - Poly[[tetra-aqua-di-MU(4)-oxalato-MU(2)-oxalato-dineo-dymium(III)] dihydrate].
AB  - The title compound, {[Nd(2)(C(2)O(4))(3)(H(2)O)(4)].2H(2)O}(n), was synthesized
      hydro-thermally in the presence of bis-(carb-oxy-ethyl-germanium) sesquioxide. It
      is isostructural with the corresponding Pr compound [Yang et al. (2009). Acta
      Cryst. E65, m1152-m1153]. The Nd(3+) cation is nine-coordinated and its
      coordination polyhedron can be described as a distorted tricapped trigonal prism.
      Two Nd(3+) ions are connected by two O atoms from two oxalate ions to give a
      dinuclear Nd(2) unit. The unit is further linked to four others via four oxalate
      ions yielding a layerparallel to (0-11). The linkages between the layers by
      neighbouring oxalate anions lead to a three-dimensional framework with channels
      along the c axis. The coordinating and free water mol-ecules are located in the
      channels and make contact with each other and the host framework by weak O-H?O
      hydrogen bonds.

PMID- 22412436
TI  - (2,2'-Bipyridine-6,6'-dicarboxyl-ato-kappaN,N',O)(6'-carb-oxy-2,2'-bipyridine-6
      carboxyl-ato-kappaN,N',O)rhodium(III).
AB  - The Rh(III) ion in the title compound,
      [Rh(C(12)H(6)N(2)O(4))(C(12)H(7)N(2)O(4))], is coordinated by four N atoms and
      two O atoms from two chelating ligands L and HL (H(2)L = 2,2'-bipyridine-6,6'
      dicarb-oxy-lic acid) to form a distorted octa-hedral geometry. Face-to-face pi
      stacking inter-actions are observed between inversion-related pyridine rings,
      with a centroid-to-centroid distance of 3.581 (1) A [the perpendicular distance
      between the rings is 3.3980 (7) A]. Inter-molecular O-H?O hydrogen bonds link
      adjacent mol-ecules into one-dimensional supra-molecular chains along the c axis,
      while several inter-molecular C-H?O inter-actions are also observed.

PMID- 22412437
TI  - catena-Poly[1-butyl-3-methyl-imidazolium [[dichlorido(methanol-kappaO)(propan-2
      ol-kappaO)lanthanate(III)]-di-MU-chlorido]].
AB  - The title compound, (C(8)H(15)N(2))[LaCl(4)(CH(3)OH)(C(3)H(7)OH)], consists of
      one 1-butyl-3-methyl-imidazolium (BMI(+)) cation and one hexa-hedral tetra
      chlorido(methanol)(propan-2-ol)lanthanate anion. The La(III) ion is eight
      coordinate, with the La(III) ion bridged by a pair of Cl atoms, so forming chains
      propagating along the a-axis direction. Each La(III) ion is further coordinated
      by two isolated Cl atoms, one methanol and one propan-2-ol mol-ecule. The
      coordinated methanol and propan-2-ol mol-ecules of the anion form O-H?Cl hydrogen
      bonds with the Cl atoms of inversion-related anions. The BMI(+) cation froms C
      H?Cl hydrogen bonds with the Cl atoms of the anion. The anions are located in the
      C faces of the triclinic unit cell, with an inversion center in the middle of the
      La(2)Cl(2) ring of the polymeric chain.

PMID- 22412438
TI  - Redetermination at 180 K of a layered lanthanide-organic framework.
AB  - The asymmetric unit of the title compound, poly[(MU(4)-{[bis-(hydrogen phospho
      natometh-yl)aza-nium-yl]meth-yl}phospho-nato)lanthanum(III)],
      [La(C(3)H(9)NO(9)P(3))](n), comprises an La(3+) center and a H(3)nmp(3-) anion
      (where H(3)nmp(3-) is a residue of partially deprotonated nitrilo-tris-(methyl
      ene-phospho-nic acid), namely {[bis-(hydrogen phospho-natometh-yl)aza-nium
      yl]meth-yl}-phos-pho-nate). This study concerns a structural redetermination
      using single-crystal X-ray diffraction data, collected at the low temperature of
      180 K, of a recently investigated material whose structural details have been
      proposed from powder X-ray diffraction studies [Silva et al. (2011 ?). J. Am.
      Chem. Soc.133, 15120-15138]. The main difference between the two models rests on
      the position of the H atoms. While two H atoms were modeled as attached to the
      same phospho-nate group in the powder determination, in the current model, the
      same H atoms are instead distributed among two of these groups. The sample
      studied was an inversion twin.

PMID- 22412439
TI  - (N,N,N',N'-Tetra-methyl-ethylenediamine-kappaN)bis-(2,4,6-trimethyl-phenolato
      kappaO)germanium(II).
AB  - In the title compound, [Ge(C(9)H(11)O)(2)(C(6)H(16)N(2))], the Ge(II) atom is
      coordinated in a distorted trigonal-pyramidal geometry by two O atoms belonging
      to two 2,4,6-trimethyl-phenolate ligands and one N atom of a tetra-methyl
      ethylenediamine ligand. Comparing the structure with published data of similar
      compounds shows that the Ge-O bonds are covalent and the Ge-N bond is
      coordinated.

PMID- 22412440
TI  - Chloridobis(1,2,3,4-tetra-hydro-1,4,6,11-tetra-aza-naphthacene-kappaN)copper(I).
AB  - In the title complex, [CuCl(C(14)H(12)N(4))(2)], the Cu(I) atom, lying on a
      twofold rotation axis, is coordinated by two N atoms of two 1,2,3,4-tetra-hydro
      1,4,6,11-tetra-aza-naphthacene ligands and one Cl atom, also lying on the twofold
      rotation axis, in a distorted trigonal-planar geometry. The complex mol-ecules
      are connected into a one-dimensional structure along [001] via N-H?N hydrogen
      bonds and further into a three-dimensional structure via N-H?Cl hydrogen bonds.
      pi-pi inter-actions between the pyrazine and benzene rings and between the
      benzene rings [centroid-centroid distances = 3.5635 (15) and 3.9128 (16) A] are
      present.

PMID- 22412441
TI  - Dichlorido(4'-phenyl-2,2':6',2''-ter-pyridyl)zinc.
AB  - The title compound, [ZnCl(2)(C(21)H(15)N(3))], was obtained from the reaction of
      ZnCl(2).4H(2)O with 4'-phenyl-terpyridine (L) and disodium 2,6-dipicolinate. The
      Zn(2+) cation is ligated by the N atoms of the tridentate L ligand and two
      chloride anions, forming a ZnN(3)Cl(2) polyhedron with a distorted trigonal
      bipyramidal coordination geometry. In the crystal, nonclassical C-H?Cl hydrogen
      bonds are observed.

PMID- 22412442
TI  - trans-Chloridobis(4-methyl-pyridine-kappaN)(4,4',4''-tri-tert-butyl-2,2':6',2''
      terpyridine-kappaN,N',N'')ruthenium(II) hexa-fluoridophosphate acetone
      monosolvate.
AB  - The title compound, [RuCl(C(6)H(7)N)(2)(C(27)H(35)N(3))]PF(6).C(3)H(6)O, was
      obtained unintentionally as the product of the reaction of 1,1'-methyl-enebis(4
      methyl-pyridinium) hexa-fluoriso-phos-phate and RuCl(3)(tpy*) (tpy* is 4,4',4''
      tri-tert-butyl-2,2':6',2''-terpyridine) in the presence of triethyl-amine and
      LiCl. The mol-ecular structure of the complex displays an octa-hedral geometry
      around the Ru(II) ion and the unit cell contains an acetone solvent mol-ecule and
      one orientationally disordered PF(6) (-) anion (occupancy ratio 0.75:0.25) which
      is hydrogen bonded to two H atoms of the tpy* ligand of the nearest
      [RuCl(pic)(2)(tpy*)](+) cation (pic is 4-methyl-pyridine). One of the tert-butyl
      groups of the tpy* ligand is also disordered over two sets of sites in a
      0.75:0.25 ratio.

PMID- 22412443
TI  - Bis[[aqua-(1H-imidazo[4,5-f][1,10]phenanthroline-kappaN,N)cadmium]bis-(MU
      pyridine-2,3-dicarboxyl-ato)-kappaN,O:O;kappaO:N,O].
AB  - In the title compound, [Cd(2)(C(7)H(3)NO(4))(2)(C(13)H(8)N(4))(2)(H(2)O)(2)], the
      Cd(II) ion is six-coordinated by two N atoms from a 1H-imidazo[4,5
      f][1,10]phenanthroline (IP) ligand, one N atom and one O atom from a pyridine-2,3
      dicarboxyl-ate (pdc) ligand, one O atom from another pdc ligand and one water mol
      ecule in a distorted octa-hedral geometry. Two Cd(II) ions are bridged by a pair
      of pdc ligands, forming a centrosymmetric dinuclear structure. Neighboring
      dinuclear units are linked by the coordinated water mol-ecules through O-H?N and
      O-H?O hydrogen bonds, forming a layer parallel to (011). The layers are further
      linked into a three-dimensional network through N-H?O hydrogen bonds. pi-pi inter
      actions between the IP ligands further stabilize the supra-molecular structure
      [centroid-centroid distances = 3.579 (3), 3.686 (3), 3.710 (3), 3.766 (3) and
      3.841 (3) A].

PMID- 22412444
TI  - {3,3'-Bis[(anthracen-9-yl)meth-yl]-1,1'-[(ethane-1,2-diyldi-oxy)bis-(ethane-1,2
      di-yl)]bis-(imidazol-2-yl-idene)}mercury(II) bis-(hexa-fluoridophosphate)
      acetonitrile disolvate.
AB  - In the title compound, [Hg(C(42)H(38)N(4)O(2))](PF(6))(2).2CH(3)CN, the Hg(II)
      cation lies on a twofold axis which is also the inter-nal symmetry element of the
      complete cationic complex. The Hg(II) cation is coordinated by two symmetry
      related C(carbene) atoms [Hg-C = 2.058 (9) A] in a nearly linear geometry, with a
      C-Hg-C angle of 175.8 (5) degrees . There are weak inter-molecular C-H?F inter
      actions in the crystal packing between an F atom of a hexa-fluoridophosphate
      anion and a -CH(2)- group of the bis-N-heterocyclic carbene ligand.

PMID- 22412445
TI  - catena-Poly[[diiodidomercury(II)]-MU(2)-2-amino-pyrazine-kappaN:N].
AB  - In the crystal of the title polymeric compound, [HgI(2)(C(4)H(5)N(3))](n), the
      Hg(II) cation is located on a twofold rotation axis and is coordinated by two I(
      ) anions and two 2-amino-pyrazine ligands in a distorted HgI(2)N(2) tetra-hedral
      geometry. In the crystal, the 2-amino-pyrazine ligand is equally disordered over
      two positions about an inversion center, and bridges the Hg(II) cations with
      pyrazine N atoms to form a polymeric chain running along the c axis. In the
      polymeric chain, the amino groups link to the coordinated I(-) anions via inter
      molecular N-H?I hydrogen bonds.

PMID- 22412446
TI  - (Benzyl phenyl sulfoxide-kappaO)-chlorido-triphenyl-tin(IV).
AB  - The Sn(IV) atom in the title compound, [Sn(C(6)H(5))(3)Cl(C(13)H(12)OS)], is
      situated within a distorted C(3)ClO trigonal-bipyramidal coordination geometry
      with a mean Sn-C distance of 2.136 (6) A and with an Sn-O distance of 2.393 (4)
      A. The Sn(IV) atom lies 0.171 (3) A out of the equatorial C(3) plane in the
      direction of the axially bound Cl atom.

PMID- 22412447
TI  - 1,1'-(Ethane-1,2-di-yl)dipyridinium dichromate(VI).
AB  - In the cation of the title salt, (C(12)H(14)N(2))[Cr(2)O(7)], the two pyridinium
      moieties are in an anti orientation with respect to one another. The dihedral
      angle between the pyridine rings is 6.3 (2) degrees . The N-C-C-N torsion angle
      is 177.5 (2) degrees . In the dianion, the Cr(VI) ions are in a slightly
      distorted tetra-hedral coordination environment and the bond angles at the
      independent Cr(VI) ions are in the ranges 105.93 (10)-110.60 (11) and 107.35 (11)
      111.07 (12) degrees . The Cr-O-Cr angle is 127.96 (12) degrees . The crystal used
      was an inversion twin with refined components of 0.510 (19) and 0.490 (19).

PMID- 22412448
TI  - (Acetyl-acetonato-kappaO,O')bis-[2-(5-methyl-3-phenyl-pyrazin-2-yl-kappaN)phen-yl
      kappaC]iridium(III).
AB  - In the title complex, [Ir(C(17)H(13)N(2))(2)(C(5)H(7)O(2))], the Ir(III) atom is
      hexa-coordinated in a distorted octa-hedral geometry by two C,N-bidentate 2-(5
      methyl-3-phenyl-pyrazin-2-yl)phenyl (mdpp) ligands and one O,O-bidentate acetyl
      acetonate ligand. The dihedral angles between the phenyl rings and the pyrazine
      ring are 9.56 (14) and 58.99 (14) degrees  for one mdpp ligand and 9.34 (14) and
      79.94 (15) degrees  for the other.

PMID- 22412449
TI  - Bis(MU(2)-4,7-dimethyl-4,7-diazadecane-1,10-dithiolato)trinickel(II)
      bis(perchlorate).
AB  - In the title compound, [Ni(3)(C(10)H(22)N(2)S(2))(2)](ClO(4))(2), the complex
      cation consists of a nickel(II) ion and two [Ni(C(10)H(22)N(2)S(2))] units with
      an N(2)S(2) tetra-dentate ligand, 3,3'-[1,2-ethane-diylbis(methyl-imino)]bis-(1
      propane-thiol-ate). The central Ni(II) ion is located on a crystallographic
      inversion centre and is bound to the four S atoms of the two
      [Ni(C(10)H(22)N(2)S(2))] units to form a linear sulfur-bridged trimetallic
      moiety. The dihedral angle between the central NiS(4) plane and the terminal
      NiN(2)S(2) plane is 145.71 (5) degrees . In the [Ni(C(10)H(22)N(2)S(2))] unit,
      the two methyl groups on the chelating N atoms are cis to each other, and the two
      six-membered N,S-chelate rings adopt a chair conformation. The Ni-S bond lengths
      and the S-Ni-S bite angles in the central NiS(4) group are similar to those in
      the [Ni(C(10)H(22)N(2)S(2))] unit.

PMID- 22412450
TI  - {MU-5-[1,3-Bis(2,4,6-trimethyl-phen-yl)-3H-imidazolium-2-yl]-2-(2-oxoethenyl
      1kappaC)furan-3-yl-2kappaC}-MU-hydrido-bis(tetra-carbonyl-rhenium) tetra-hydro
      furan 0.67-solvate.
AB  - The title complex, [Re(2)(C(27)H(25)N(2)O(2))H(CO)(8)].0.67C(4)H(8)O, was formed
      as a product in the reaction of a rhenium(I)-Fischer carbene complex with a free
      NHC carbene. The coordination environment about the two Re atoms is slightly
      distorted octahedral, including a bridging H atom. The imidazolium and furan
      groups are almost coplanar, whereas the mesityl substituents show an almost
      perpendicular arrangement with respect to both heterocyclic units. Mol-ecules of
      the complex pack in such a way as to form channels parallel with the bc unit-cell
      face diagonal running through the unit face diagonal. These channels are
      partially occupied by tetra-hydro-furan solvent mol-ecules.

PMID- 22412451
TI  - Aqua-(benzamidato-kappaN)bis-[3,5-difluoro-2-(pyridin-2-yl)phenyl
      kappaC]iridium(III) methanol monosolvate.
AB  - In the title compound, [Ir(C(11)H(6)F(2)N)(2)(C(7)H(6)NO)(H(2)O)].CH(3)OH, the
      Ir(III) ion adopts an octa-hedral geometry, and is coordinated by two 3,5
      difluoro-2-(pyridin-2-yl)phenyl ligands, one mol-ecule of water and one
      benzamidate anion. The two 2-(4,6-difluoro-phen-yl)pyridyl ligands are arranged
      in a cis-C,C' and trans-N,N' fashion. Additionally, there is a bystanding
      methanol mol-ecule outside the coordination sphere of the Ir(III) ion. In the
      crystal, mol-ecules of the title compound are linked by O-H?O and O-H?N hydrogen
      bonds. One F atom of each ligand is equally disordered over two sites. The C atom
      of the solvent molecule is likewise disordered over two sites in a 0.589
      (11):0.411 (11) ratio.

PMID- 22412452
TI  - Dichlorido{2-[(2,6-dimethyl-phen-yl)imino-meth-yl]pyridine-kappaN,N'}zinc.
AB  - In the asymmetric unit of the title compound, [ZnCl(2)(C(14)H(14)N(2))], the
      central Zn(II) ion is four-coordinated in a distorted tetra-hedral environment by
      two N atoms of the ligand 2-[(2,6-dimethyl-phen-yl)imino-meth-yl]pyridine and two
      chloride anions. In the crystal, adjacent mol-ecules are connected through C-H?Cl
      hydrogen bonds between a C-H group of the ligand and a Cl(-) anion, leading to a
      chain-like structure along the b direction.

PMID- 22412453
TI  - Tris(3-nitro-pentane-2,4-dionato-kappaO,O')-cobalt(III).
AB  - The structure of the title compound, [Co(C(5)H(6)NO(4))(3)], consists of a
      Co(III) ion octahedrally coordinated by three bidentate 3-nitro-pentane-2,4
      dionate ligands. The complex was prepared via the nitration of tris-(2,4-penta
      nedionato-kappa(2)O,O')cobalt(III) with a solution of copper(II) nitrate in
      glacial acetic acid. The central C atom and the nitro group of one 3-nitro
      pentane-2,4-dionate ligand are disordered over two positions with an occupancy
      ratio of 0.848 (4):0.152 (4). A second nitro group is also disordered over two
      orientations with an occupancy ratio of 0.892 (7):0.108 (7). Two of the ligand
      methyl groups form C-H?O inter-actions with two different nitro groups to form
      chains running along the c axis. Additional C-H?O inter-actions are found between
      ligand methyl groups and the cobalt-bound O atoms, also resulting in the
      formation of chains along the c axis.

PMID- 22412454
TI  - Dichloridobis(thio-urea-kappaS)nickel(II).
AB  - The title complex, [NiCl(2)(CH(4)N(2)S)(2)], has been synthesized from the
      previously reported (diamino-methyl-idene)sulfonium chloride-thio-urea (3/2) salt
      [Zouihri (2012b ?). Acta Cryst. E68, o257]. The Ni(II) ion is coordinated in a
      distorted tetra-hedral geometry by two mol-ecules of thio-urea [Ni-S = 2.3079 (7)
      and 2.3177 (6) A] and two chloride anions [Ni-Cl = 2.2516 (7) and 2.2726 (7) A].
      The bond angles at the Ni atom lie between 96.69 (2) and 115.40 (3) degrees ,
      while the dihedral angle between the mean planes of the two thio-urea ligands is
      6.36 (15) degrees . The crystal structure is characterized by intra- and inter
      molecular N-H?Cl hydrogen bonds, which lead to the formation of two-dimensional
      networks lying parallel to the ab plane. The networks are linked via classical N
      H?Cl and N-H?S hydrogen bonds, forming a three-dimensional arrangement.

PMID- 22412455
TI  - {MU-2-[4-(Benzothia-zol-2-yl)benz-yl]-2-aza-propane-1,3-dithiol-ato
      1:2kappaS,S':S,S'}bis-[tricarbonyl-iron(I)].
AB  - The title compound, [Fe(2)(C(16)H(14)N(2)S(3))(CO)(6)], was prepared as the
      biomimetic model for the active site of iron-only hydrogenase. The structure is
      similar to the diiron subsite of the iron-only hydrogenase active site, and
      contains a diiron-aza-dithiol-ate moiety in which a boat six-membered ring is
      fused with a chair six-membered ring. The substituted benzyl group attached to
      the bridging N atom resides in an equatorial position. The sum of the C-N-C
      angles around this N atom [331.9 (12) degrees ] indicates sp(3) hybridization.

PMID- 22412456
TI  - {S-Benzyl 3-[(6-methyl-pyridin-2-yl)-methyl-idene]dithio-carbazato}nickel(II)
      monohydrate.
AB  - The structure of the title compound, [Ni(C(15)H(14)N(3)S(2))(2)].H(2)O, has one
      mol-ecule in the asymmetric unit, along with a solvent water mol-ecule. The two
      different Schiff base moieties coordinate to the central Ni(II) ion as tridentate
      N,N',S-chelating ligands, creating a six-coordinate distorted octa-hedral
      environment [the smallest angle being 77.43 (7) degrees  and the widest angle
      being 169.99 (7) degrees ]. The mean planes of the two ligands are nearly
      orthogonal to each other with an angle of 89.53 (6) degrees . The packing of the
      complex is supported by O-H?N and O-H?S hydrogen bonding between the solvent
      water mol-ecule and the uncoordinated N and S atoms of neighbouring ligands.

PMID- 22412458
TI  - Bis[N-(2-hy-droxy-eth-yl)-N-methyl-dithio-carbamato-kappaS][2,4,6-tris-(pyridin-2
      yl)-1,3,5-triazine-kappaN,N,N]zinc dioxane sesquisolvate.
AB  - The asymmetric unit of the title compound,
      [Zn(C(4)H(8)NOS(2))(2)(C(18)H(12)N(6))].1.5C(4)H(8)O(2), comprises a Zn
      containing mol-ecule and one and a half dioxane mol-ecules as one of the solvent
      mol-ecules is located about a crystallographic inversion centre. The
      approximately square-pyramidal N(3)S(2) donor set is defined by two monodentate
      dithio-carbamate ligands and two pyridine and one triazine N atom from the
      tridentate triazine ligand. Mol-ecules are connected into a supra-molecular array
      via O-H?S and O-H?N hydrogen bonds. These stack along the b axis and the solvent
      mol-ecules reside in the channels thus formed.

PMID- 22412457
TI  - catena-Poly[[(1,10-phenanthroline)cobalt(II)]-di-MU-azido].
AB  - In the crystal structure of the binuclear title complex,
      [Co(N(3))(2)(C(12)H(8)N(2))](n), each Co(II) cation is coordinated by two N atoms
      from one chelating 1,10-phenanthroline ligand and four azide ligands in a
      slightly distorted octa-hedral coordination. The two Co(II) cations of the
      binuclear complex are related by an inversion centre and are bridged by two
      symmetry-related azide ligands in both MU(1,1) and MU(1,3) modes. The MU(1,3)
      bridging mode gives rise to an infinite one-dimensional chain along the a axis,
      whereas the MU(1,1) bridging mode is responsible for the formation of the
      binuclear Co(II) complex.

PMID- 22412459
TI  - (2,2'-Bipyridine-kappaN,N')bis-(4-chloro-benzoato-kappaO)zinc.
AB  - In the title compound, [Zn(C(7)H(4)ClO(2))(2)(C(10)H(8)N(2))], the Zn(II) atom is
      coordinated by two O atoms from two 4-chloro-benzoate ligands and two N atoms
      from a chelating 2,2'-bipyridine (bpy) mol-ecule in a distorted N(2)O(2) tetra
      hedral geometry. The Zn(II) atom is located on a twofold rotation axis, which
      also passes through the mid-point of the central C-C bond of the bpy ligand. In
      the crystal, weak C-H?O hydrogen bonds and pi-pi stacking inter-actions between
      the pyridine rings of the bpy ligands [centroid-centroid distance = 3.642 (3) A]
      link the complex mol-ecules into a two-dimensional supra-molecular structure
      parallel to (100). An intra-molecular C-H?O hydrogen bond is also observed.

PMID- 22412460
TI  - Dichloridobis(4-pyridylmethyl 1H-pyrrole-2-carboxyl-ate-kappaN)zinc.
AB  - In the title mol-ecule, [ZnCl(2)(C(11)H(10)N(2)O(2))(2)], the Zn(II) ion,
      situated on a twofold axis, is in a distorted tetra-hedral coordination
      environment formed by two chloride anions and two pyridine N atoms of the two
      organic ligands. In the pyrrole-2-carboxyl-ate unit, the pyrrole N-H group and
      the carbonyl group point approximately in the same direction. The dihedral angle
      between the two pyridine rings is 54.8 (3) degrees . The complex mol-ecules are
      connected into chains extending along [101] by N-H?Cl hydrogen bonds. The chains
      are further assembled into (-101) layers by C-H?O and C-H?Cl inter-actions.

PMID- 22412461
TI  - Bis(hydrazin-1-ium) bis-(MU(2)-pyridazine-3,6-dicarboxyl-ato)bis-(aqua-lithiate)
      octa-aqua-bis-(MU(3)-pyridazine-3,6-dicarboxyl-ato)tetra-lithium.
AB  - The unit cell of the title compound,
      (N(2)H(5))(2)[Li(2)(C(6)H(2)N(2)O(4))(2)(H(2)O)(2)].[Li(4)(C(6)H(2)N(2)O(4))(2)(H
      2)O)(8)], comprises two centrosymmetric complexes, one double negatively charged
      and one neutral, and two mono-protonated hydrazine cations. The anionic complex
      molecule is a dimer, built of a pair of symmetry-related pyridazine-3,6
      dicarboxyl-ate ligands and a pair of Li(I) ions, each coordinated by two N,O
      chelating sites donated by a ligand mol-ecule and an aqua O atom at the apical
      position. The penta-coordination around the Li(I) ions is partway between a
      trigonal-bipyramidal and a square-pyramidal arrangement. The two carb-oxy-lic
      acid groups of the ligand are deprotonated and one carboxyl-ate O atom of each
      group is not involved in the coordination, and this applies to both the anionic
      and the neutral complex. The neutral complex molecule is also composed of a pair
      of Li(I) ions and a pair of ligand mol-ecules related by a centre of symmetry.
      They form a dimeric core in which the penta-coordination of the Li(I) ions
      includes two N,O-bonding groups donated by two ligands and an aqua O atom. The
      penta-coordination is described as partway between a trigonal-bipyramidal and a
      square-pyramidal arrangement. The coordinated carboxyl-ate group is bidentate
      bridging, forming with an Li(H(2)O)(3) unit a neutral tetra-meric mol-ecule. The
      coordination of the tetra-coordinated Li(I) ion shows a slightly distorted tetra
      hedral geometry. An extended system of O-H?O and N-H?O hydrogen bonds contributes
      to the stability of the crystal structure.

PMID- 22412462
TI  - MU-4,4'-Bipyridine-bis-[aqua-(4-hy-droxy-pyridine-2,6-dicarboxyl-ato)copper(II)].
AB  - The title compound, [Cu(2)(C(7)H(3)NO(5))(2)(C(10)H(8)N(2))(H(2)O)(2)], exhibits
      a centrosymmetric binuclear molecule. Each completely deprotonated 4-hy-droxy
      pyridine-2,6-dicarb-oxy-lic acid mol-ecule assumes a tridentate chelating
      coordination mode. The square-pyramidal coordination geometry around the Cu(II)
      ion is completed by the bridging bipyridine ligand and an apical water molecule.
      Adjacent complexes are connected via O-H?O and C-H?O hydrogen bonds to generate a
      three-dimensional supra-molecular structure.

PMID- 22412463
TI  - Bis(1H-benzimidazole-kappaN)bis-[2-(naphthalen-1-yl)acetato
      kappaO,O']manganese(II) monohydrate.
AB  - In the title compound, [Mn(C(12)H(9)O(2))(2)(C(7)H(6)N(2))(2)].H(2)O, the Mn(II)
      ion is located on a twofold rotation axis and six-coordinated, displaying a
      distorted MnN(2)O(4) octa-hedral geometry. The crystal packing is stabilized by N
      H?O hydrogen bonds, which give rise to a one-dimensional structure along [001],
      and pi-pi inter-actions between the imidazole rings and between the benzene rings
      of the 2-(naphthalen-1-yl)acetate ligands [centroid-centroid distances = 3.761
      (3) and 3.728 (4) A]. The contribution of the electron density associated with
      the disordered water molecules was not considerd in the final structure model.

PMID- 22412464
TI  - (Acetato-kappaO)diaqua-[2-(1H-benzotriazol-1-yl)acetato-kappaO](1,10
      phenanthroline-kappaN,N')manganese(II) dihydrate.
AB  - In the hydrated title complex,
      [Mn(C(8)H(6)N(3)O(2))(CH(3)CO(2))(C(12)H(8)N(2))(H(2)O)(2)].2H(2)O, the Mn(II)
      atom is coordinated by two N atoms from a 1,10-phenanthroline ligand, two water O
      atoms, a monodentate acetate anion and an O-monodentate 2-(1H-benzotriazol-1
      yl)acetate ligand, resulting in a distorted cis-MnN(2)O(4) octa-hedral
      coordination geometry. The water O atoms are in a trans arrangement and one of
      them forms an intra-molecular O-H?O hydrogen bond to the uncoordinated O atom of
      the acetate ion. In the crystal, the complex mol-ecules and water mol-ecules are
      connected by O-H?O and O-H?N hydrogen bonds to generate a three-dimensional
      network.

PMID- 22412465
TI  - Bis{MU-[4-(1,3-benzothia-zol-2-yl)phen-yl]methane-thiol-ato-kappaS,S':S,S'}bis
      [tricarbonyl-iron(I)](Fe-Fe).
AB  - The title compound, [Fe(2)(C(14)H(10)NS(2))(2)(CO)(6)], was synthesized as a
      structural and biochemical model for the active site of [FeFe]-hydrogenase. The
      bond lengths (Fe-Fe, Fe-S and Fe-C) and angles (C-Fe-Fe and Fe-S-Fe) are within
      expected ranges. The S?S distance [2.9069 (12) A] and the dihedral angle between
      two Fe-S-Fe planes [78.5 (3) degrees ] of the butterfly-shaped Fe(2)S(2) core are
      enlarged compared with related bridged dithiol-ate diiron analogues. The
      calculated 4-benzothia-zolebenzyl best planes are almost parallel [dihedral angle
      = 3.7 (7) degrees ].

PMID- 22412466
TI  - [MU-Bis(diphenyl-phosphan-yl)methane]-tricarbon-yl(MU-p-toluene-sulfonyl-meth-yl
      isocyanato)(triphenyl-phosphane)ironplatinum(Fe-Pt).
AB  - The title compound, [FePt(C(9)H(9)NO(2)S)(C(18)H(15)P)(C(25)H(22)P(2))(CO)(3)],
      represents a rare example of an isonitrile-bridged heterobimetallic complex (here
      Pt and Fe) and is an inter-esting precursor for the preparation of
      heterodinuclear MU-amino-carbyne complexes, since the basic imine-type N atom of
      the MU(2)-C=N-R ligand readily undergoes addition with various electrophiles to
      afford iminium-like salts. In the crystal, the almost symmetrically bridging
      MU(2)-C=N-R ligand (neglecting the different atomic radii of Fe and Pt) is
      strongly bent towards the Fe(CO)(3) fragment, with a C=N-R angle of only 121.1
      (4) degrees .

PMID- 22412467
TI  - Tris(tetra-butyl-ammonium) hexa-kis-(tert-butane-thiol-ato-kappaS)hepta-MU(3)
      chlorido-MU(3)-sulfido-hexa-molybdate dihydrate.
AB  - The octa-hedral cluster core of the anion in the structure of the title compound,
      (C(16)H(36)N)(3)[Mo(6)(C(4)H(9)S)(6)(MU(3)-Cl)(7)(MU(3)-S)].2H(2)O, has -3 site
      symmetry. Two MU(3)-Cl atoms fully occupy positions in the cluster core, while
      the remaining six positions are statistically occupied by Cl and S atoms in a 1:5
      ratio. The fully occupied Cl-atom positions are located on sites with 3 symmetry,
      and the N atom of tetra-butyl-ammonium cation is located on a site with 2
      symmetry. The structure contains also two disordered solvent water mol-ecules,
      one of which is located on a threefold rotation axis and the other in a general
      position, both with an occupancy of 0.25. The water mol-ecules are localized in
      cavities formed by the tetra-butyl-ammonium cations and the tert-butane-thiol-ate
      groups. The metal clusters are stacked in a cubic close packing arrangement along
      [001].

PMID- 22412468
TI  - catena-Poly[ammonium (cadmium-tri-MU-thio-cyanato-kappaS:N;kappaN:S)-1,4,10,13,16
      hexa-oxa-cyclo-octa-decane (1/1)].
AB  - In the title compound, {(NH(4))[Cd(NCS)(3)].C(12)H(24)O(6)}(n), the Cd(2+) ion,
      the ammonium cation, one of the SCN(-) ligands and the macrocycle are located on
      mirror planes. The thiocyanate anions act as bridging ligands between the Cd(II)
      ions, leading to a polymeric chain arrangement extending along [001] around a
      twofold screw axis. The ammonium ions are contained within the bowl of the
      macrocycle via extensive N-H?O hydrogen bonding.

PMID- 22412469
TI  - Bis(MU-propan-2-olato-kappaO:O)bis-[chlor-ido(propan-2-ol-kappaO)bis-(pro-pan-1
      ol-ato-kappaO)tin(IV)].
AB  - The binuclear centrosymmetric title compound,
      [Sn(2)(C(3)H(7)O)(6)Cl(2)(C(3)H(8)O)(2)], exhibits an edge-shared double
      octahedral exhibits an edge-shared octa-hedral structure, which is distorted
      owing to the presence of asymmetric intra-molecular hydrogen bonds between the
      axially coordinated isopropanol and isopropoxide ligands. The H atom of the hy
      droxy group is located nearer to an isoprop-oxy group with the longest Sn-O bond
      [2.1789 (17) A].

PMID- 22412470
TI  - Chlorido[2-({[2-(diphenyl-phosphan-yl)-benzyl-idene]amino}-meth-yl)thio-phene
      kappaN,P]methyl-palladium(II).
AB  - In the title compound, [Pd(CH(3))Cl(C(24)H(20)NPS)], the Pd(II) ion is
      coordinated in a distorted square-planar environment which includes the P and N
      atoms of the bis-chelating ligand. The thio-phene ring is rotationally ordered,
      unlike in the majority of crystal structures containing this group.

PMID- 22412471
TI  - catena-Poly[bis-(dibenzyl-ammonium) [[dichloridomercurate(II)]-MU-sulfato
      kappaO:O']].
AB  - The structure of the title compound, (C(14)H(16)N)(2)[HgCl(2)(SO(4))], consists
      of an infinite chain propagating along the c direction, containing Hg(II) ions
      tetra-coordinated by two bridging O atoms of bis-monodentate sulfate anions and
      two chloride ligands. In the the crystal, N-H?O hydrogen bonding between the
      cations and the anionic chains consolidates the packing. The crystal structure
      was determined from an inversion twin with approximately equal twin domains.

PMID- 22412472
TI  - Bis[1-cyclo-propyl-6-fluoro-4-oxo-7-(1-piperazin-4-ium-1-yl)-1,4-dihydro
      quinoline-3-carboxyl-ate-kappaO,O]bis-(nitrato-kappaO)copper(II).
AB  - In the title complex, [Cu(NO(3))(2)(C(17)H(18)FN(3)O(3))(2)], the Cu(II) ion is
      located on an inversion center. It exhibits a distorted octa-hedral geometry,
      being coordinated by six O atoms, four from two ciprofloxacin ligand mol-ecules
      (L), which act as bidentate ligands, and two from two nitrate anions. In the
      ligand, the piperazine ring has a chair conformation and the quinoline system is
      essentially planar [maximum deviation = 0.097 (2) A]. One of the nitrate O atoms
      is disordered over two positions [occupancy ratio = 0.51 (6):0.49 (6)]. There is
      a C-H?F inter-action in the complex. In the crystal, mol-ecules are linked via N
      H?O hydrogen bonds generating a two-dimensional network lying parallel to (111).
      The presence of C-H?O inter-actions leads to the formation of a three-dimensional
      structure. The title complex was prepared by hydro-thermal synthesis, and the
      hexa-hydrate form of this complex, synthesized by conventional methods, has been
      reported previously [Hernandez-Gil et al. (2009 ?). Polyhedron, 28, 138-144].

PMID- 22412473
TI  - Bis(4-methyl-N-{(2Z,4E)-4-[(4-methyl-phen-yl)imino]-pent-2-en-2
      yl}anilinido)zinc.
AB  - The title compound, [Zn(C(19)H(21)N(2))(2)], appears to be the first example of a
      zinc complex supported by two beta-diketiminate (nacnac) ligands. This complex
      crystallizes with a distorted tetra-hedrally coordinated Zn(II) atom that diposes
      the two nacnac ligands approximately orthogonally to one another [angle between
      the two N-Zn-N mean planes is 89.91 (10) degrees ], with average Zn-N bond
      lengths of 1.992 (4) A.

PMID- 22412474
TI  - Trichloridotris{N-[phen-yl(pyridin-2-yl)-methyl-idene]hydroxyl-amine
      kappaN,N'}samarium(III).
AB  - The Sm(III) ion in the title compound, [SmCl(3)(C(12)H(10)N(2)O)(3)], shows a
      coordination number of nine with a slightly distorted tricapped trigonal
      prismatic geometry based on a Cl(3)N(6) donor set. The mol-ecular structure is
      stabilized by three intra-molecular O-H?Cl hydrogen bonds.

PMID- 22412475
TI  - Bis{MU-2-[bis-(pyridin-2-yl)methyl-idene]hydrazinecarbothio-amidato}bis-[bromido
      copper(II)] methanol disolvate.
AB  - In the centrosymmetric binuclear title compound,
      [Cu(2)Br(2)(C(12)H(10)N(5)S)(2)].2CH(3)OH, the Cu(II) ion adopts a slightly dis
      torted square-pyramidal coordination geometry. The hydrazine carbothio-amide
      moiety and one of the pyridyl rings together adopt an almost planar arrangement,
      with a maximum deviation of 0.052 (4) A for the C atom of the thio-urea moiety.
      There are two mol-ecules of methanol solvent per complex in the asymmetric unit.
      The nonconventional intra-molecular C-H?Br hydrogen bonds make the mol-ecule more
      rigid, whereas the conventional N-H?N and O-H?Br inter-molecular hydrogen-bonding
      inter-actions, supported with N-H?pi inter-actions, establish a supra-molecular
      linkage among the mol-ecules in the crystal. An intermolecular C-H?O inter-action
      is also present.

PMID- 22412476
TI  - Bis[4-amino-N-(pyrimidin-2-yl)benzene-sulfonamidato](1,10
      phenanthroline)nickel(II).
AB  - In the mononuclear title compound, [Ni(C(10)H(9)N(4)O(2)S)(2)(C(12)H(8)N(2))],
      the Ni(II) atom has a distorted octa-hedral coordination geometry comprising four
      N atoms from two 4-amino-N-(pyrimidin-2-yl)benzene-sulfonamidate ligands and two
      N atoms from a 1,10-phenanthroline ligand. In the crystal, mol-ecules are
      connected into a three-dimensional supra-molecular network via N-H?O hydrogen
      bonds and weak C-H?O and C-H?N contacts.

PMID- 22412477
TI  - Tetra-kis(MU-naphthalene-1-acetato-kappaO:O')bis-[(N,N-dimethyl-formamide
      kappaO)copper(II)].
AB  - The asymmetric unit of the title compound,
      [Cu(2)(C(12)H(9)O(2))(4)(C(3)H(7)NO)(2)], contains two independent
      centrosymmetric dinuclear copper(II) complexes. The central paddle-wheel units
      are formed by four bridging bidentate naphthalene-1-acetate ligands with two
      dimethyl-formamide ligands in the axial positions. The unique Cu(II) ions have
      slightly distorted square-pyramidal coordination geometries. One of the
      naphthalene rings is disordered over two sets of sites, with refined occpancies
      of 0.535 (4) and 0.465 (4).

PMID- 22412478
TI  - (E)-Isopentyl 3-(3,4-dihy-droxy-phen-yl)-acrylate.
AB  - The title compound, C(14)H(18)O(4), a derivative of caffeic acid, has an E
      configuration about the C=C bond. The benzene ring is almost coplanar with the
      C=C-C(O)-O-C linker [maximum deviation = 0.050 (2) A], making a dihedral angle of
      only 4.53 (2) degrees . In the mol-ecule, the adjacent hy-droxy groups form an O
      H?O inter-action. In the crystal, mol-ecules are linked by O-H?O hydrogen bonds,
      generating a chain propagating in the [110] direction.

PMID- 22412479
TI  - (4R*,5R*)-2-(4-Meth-oxy-phen-yl)-1,3-dioxolane-4,5-dicarboxamide.
AB  - In the title compound, C(12)H(14)N(2)O(5), the five-membered 1,3-dioxolane ring
      has a twisted conformation. In the crystal, N-H?O and C-H?O hydrogen bonds link
      the mol-ecules into a two-dimensional network lying parallel to the ab plane.
      There are also C-H?pi inter-actions present in the crystal structure.

PMID- 22412480
TI  - 2-Hy-droxy-N'-(5-hy-droxy-2-nitro-benzyl-idene)-3-methyl-benzohydrazide.
AB  - The title compound, C(15)H(13)N(3)O(5), was prepared by condensing 5-hy-droxy-2
      nitro-benzaldehyde and 2-hy-droxy-3-methyl-benzohydrazide in methanol. The two
      benzene rings make a dihedral angle of 3.9 (3) degrees . An intra-molecular O-H?O
      hydrogen bond is observed. The crystal structure is stabilized by inter-molecular
      O-H?O and N-H?O hydrogen bonds, and C-H?O and pi-pi inter-actions [centroid
      centroid distances = 3.5658 (17)-3.9287 (19) A].

PMID- 22412481
TI  - 7'-(2,5-Dimeth-oxy-phen-yl)-1',3',5',6',7',7a'-hexa-hydro-dispiro-[indan-2,5'
      pyrrolo-[1,2-c][1,3]thia-zole-6',2''-indan]-1,3,1''-trione.
AB  - In the title compound, C(30)H(25)NO(5)S, all the five-membered rings are in
      envelope conformations with the spiro and methylene C atoms as the flap atoms.
      Intra-molecular C-H?O inter-actions stabilize the mol-ecular structure and form
      S(6) and S(7) ring motifs. The mean plane through the hexa-hydro-pyrrolo-[1,2
      c]thia-zole ring [r.m.s deviation of 0.0393 (1) A] makes dihedral angles of 60.92
      (5), 88.33 (4) and 84.12 (4) degrees  with the terminal benzene ring and the mean
      planes of the mono and di-oxo substituted indan rings, respectively. Mol-ecules
      are linked by inter-molecular C-H?O inter-actions into a three-dimensional
      network. In addition, C-H?pi and pi-pi inter-actions [centroid-to-centroid
      distance = 3.4084 (8) A] further stabilize the crystal structure.

PMID- 22412482
TI  - (E)-4-Meth-oxy-N'-(3,4,5-trimeth-oxy-benzyl-idene)benzohydrazide.
AB  - In the asymmetric unit of the title compound, C(18)H(20)N(2)O(5), there are two
      crystallographic independent mol-ecules. Both mol-ecules are twisted; the
      dihedral angle between the two benzene rings is 7.2 (5) degrees  in one mol
      ecule, whereas it is 85.9 (4) degrees  in the other. Of the three meth-oxy groups
      in the 3,4,5-trimeth-oxy-phenyl unit, two meth-oxy groups at meta positions are
      approximately coplanar with the benzene plane [C-O-C-C torsion angles of -2.3
      (13)-4.8 (11) degrees ], but the other meth-oxy, at the para position, is out of
      the plane [C-O-C-C of 72.8 (9) degrees  in one mol-ecule and -77.5 (9) degrees 
      in the other]. In the crystal, mol-ecules are linked by N-H?O hydrogen bonds and
      weak C-H?O inter-actions into tapes along the b axis. C-H?pi inter-actions are
      also present.

PMID- 22412483
TI  - 2-((E)-{3-[(E)-2-Hy-droxy-3,5-diiodo-benzyl-idene-amino]-2,2-dimethyl-prop
      yl}imino-meth-yl)-4,6-diiodo-phenol.
AB  - The asymmetric unit of the title compound, C(19)H(18)I(4)N(2)O(2), comprises a
      potentially tetra-dentate Schiff base ligand. The disordered H atoms on the N and
      O atoms were refined with site occupancies of 0.54 (8)/0.46 (8) and 0.59 (7)/0.41
      (7), respectively. The dihedral angle between the benzene rings is 73.3 (3)
      degrees . Intra-molecular O-H?N and N-H?O hydrogen bonds make S(6) ring motifs.
      Short I?I [3.8919 (7) A] and I?Cg [Cg is a ring centroid; 3.911 (2) A] contacts
      are present in the crystal structure. The crystal structure is further stabilized
      by inter-molecular pi-pi inter-actions [centroid-to-centroid distance = 3.827 (3)
      A].

PMID- 22412484
TI  - 4-{4-[(E)-(2-Hy-droxy-phen-yl)imino-methyl]phen-oxy}benzene-1,2-di-carbo-nitrile.
AB  - The asymmetric unit of the title compound, C(21)H(13)N(3)O(2), contains two
      independent mol-ecules with a similar structure. In one mol-ecule, the central
      benzene ring is oriented with respect to the terminal benzene rings at 27.23 (7)
      and 67.96 (7) degrees ; in the other mol-ecule, the corresponding dihedral angles
      are 12.42 (7) and 64.55 (7) degrees . In both molecules, there is a short O-H?N
      interaction involving the OH group and the adjacent N atom. In the crystal, there
      are O-H?N hydrogen bonds, and C-H?O and N-H?O interactions linking the molecules
      to form a three-dimensional network. pi-pi stacking between the pyridine and
      benzene rings and between the benzene rings [centroid-centroid distances = 3.989
      (2), 3.705 (2) and 3.607 (2) A] may further stabilize the structure. A weak C
      H?pi inter-action is present in the crystal.

PMID- 22412485
TI  - 2-(4-Meth-oxy-benzyl-idene)-2H-1,3-benzodithiole 1,1,3,3-tetra-oxide.
AB  - The title compound, C(15)H(12)O(5)S(2), crystallizes with two mol-ecules in the
      asymmetric unit. In both mol-ecules, the 1,3-benzodithiole plane and the aryl
      ring of the anisyl group are not quite coplanar; the corresponding dihedral
      angles are 20.4 (1) and 18.0 (1) degrees . pi-Stacking [with centroid-centroid
      distances between 3.5440 (14) and 3.8421 (14) A] takes place along [100] between
      the alternating benzodithiole benzene rings of symmetrically independent mol
      ecules, and also between the anisyl groups of symmetrically related mol-ecules.
      Furthermore, mol-ecules are linked through C-H?O inter-actions.

PMID- 22412486
TI  - Di-tert-butyl (2R,3R)-2-{[(2E)-3-(4-acet-yloxy-3-meth-oxy-phen-yl)prop-2-eno-yl]
      oxy}-3-hy-droxy-butane-dioate.
AB  - In the title mol-ecule, C(24)H(32)O(10), one tert-butyl ester group is folded
      towards the central benzene ring while the other is directed away. The acetyl
      group is almost perpendicular to the benzene ring to which it is connected [C-C-O
      C torsion angle = 90.4 (12) degrees ]. The conformation about the ethene bond
      [1.313 (7) A] is E. The atoms of the benzene ring and its attached ester group
      and part of the hy-droxy tert-butyl ester side chain are disordered over two sets
      of sites in a 50:50 ratio. Linear supra-molecular chains along the a axis
      mediated by hy-droxy-carbonyl O-H?O hydrogen bonds feature in the crystal
      packing. The same H atom also partakes in an intra-molecular O-H?O inter-action.

PMID- 22412487
TI  - (E)-2-({2-[(E)-(Hy-droxy-imino)-meth-yl]phen-oxy}meth-yl)-3-p-tolyl
      acrylonitrile.
AB  - In the title compound, C(18)H(16)N(2)O(2), the hy-droxy-ethanimine group is
      essentially coplanar with the ring to which it is attached (C-C-N-O torsion angle
      = -176.9 degrees ). Mol-ecules are linked into cyclic centrosymmetric R(2) (2)(6)
      dimers via O-H?N hydrogen bonds.

PMID- 22412488
TI  - tert-Butyl 2-(1H-benzimidazol-1-yl)acetate.
AB  - In the title compound, C(13)H(16)N(2)O(2), the planes of the benzimidazole ring
      system and the acetate O-C=O fragment make a dihedral angle of 84.5 (3) degrees .
      In the crystal, mol-ecules are connected through C-H?N hydrogen bonds to form
      infinite chains in the [-110] direction.

PMID- 22412489
TI  - N-(4-Methyl-benzo-yl)-2-nitro-benzene-sulfonamide.
AB  - The asymmetric unit of the title compound, C(14)H(12)N(2)O(5)S, contains two
      independent mol-ecules. The dihedral angles between the aromatic rings are 82.03
      (9) and 79.47 (8) degrees  in the two independent mol-ecules. In the crystal, the
      two mol-ecules in the asymmetric unit are linked into dimers via pairs of N
      H?O(S) hydrogen bonds to generate C(4) chains.

PMID- 22412490
TI  - 3,3'-[1,2-Phenyl-enebis(methyl-ene)]bis-(1-ethyl-benzimidazolium) dibromide.
AB  - In the title mol-ecular salt, C(26)H(28)N(4) (2+).2Br(-), the central benzene
      ring makes dihedral angles of 76.75 (11) and 82.40 (10) degrees  with the pendant
      benzimidazole rings. The corresponding angle between the benzimidazole rings is
      57.03 (9) degrees . In the crystal, the cations and anions are linked via C-H?Br
      hydrogen bonds, forming sheets lying parallel to the bc plane. The crystal
      structure also features weak C-H?pi inter-actions.

PMID- 22412491
TI  - 4-Chloro-phenyl 2-oxo-2H-chromene-3-carboxyl-ate.
AB  - In title compound, C(16)H(9)ClO(4), the coumarin ring system is approximately
      planar [maximum deviation = 0.056 (1) A] and is oriented with respect to the
      benzene ring at an angle of 22.60 (7) degrees . Inter-molecular C-H?O hydrogen
      bonding is present in the crystal.

PMID- 22412492
TI  - 2-Benzyl-3-phenyl-1-(pyridin-2-yl)propan-1-one.
AB  - Mol-ecules of the title compound, C(21)H(19)NO, assume an approximate propellar
      shape, with the three aromatic rings being nearly perpendicularly aligned with
      respect to the plane formed by the C atoms that are connected to the methine C
      atom [dihedral angles: pyridyl 79.82 (4) degrees , phenyl 80.12 (3) degrees  and
      phenyl 86.93 (3) degrees ].

PMID- 22412493
TI  - 1-(Pyridin-2-yl)-2-[2-(trifluoro-meth-yl)benz-yl]-3-[2-(trifluoro-meth-yl)phen
      yl]propan-1-one.
AB  - The title compound, C(23)H(17)F(6)NO, crystallizes with two mol-ecules in the
      asymmetric unit. The mol-ecules assume an approximate propellar shape, with the
      three aromatic rings being bent with respect to the plane formed by the C atoms
      that are connected to the methine C atom [dihedral angles: pyridyl 67.49 (3)
      degrees , phenyl 56.82 (4) degrees  and phenyl 77.21 (6) degrees  in one mol
      ecule, and corresponding angles of 71.60 (6), 53.68 (4) and 77.53 (6) degrees  in
      the second mol-ecule].

PMID- 22412494
TI  - Dibenzyl-aza-nium chloride.
AB  - In the title salt, C(14)H(16)N(+).Cl(-), the complete cation and complete anion
      are generated by the application of mirror symmetry. The mol-ecule is nonplanar,
      as seen in the dihedral angle between the terminal phenyl rings [70.92 (5)
      degrees ]. In the crystal, N-H?Cl hydrogen bonds involving both aza-nium H atoms
      link the ions into a zigzag supra-molecular chain along [100].

PMID- 22412495
TI  - (E)-2-{[(2-(Trifluoro-meth-yl)phen-yl]imino-meth-yl}phenol.
AB  - In the crystal of the title compound, C(14)H(10)F(3)NO, intra-molecular O-H?N and
      O-H?F hydrogen bonds generate S(6) and S(10) intramolecular hydrogen-bonded
      rings. The dihedral angle between the planes of the aromatic rings is 13.00 (14)
      degrees .

PMID- 22412496
TI  - (1R*,2S*,4S*,5R*)-Cyclo-hexane-1,2:4,5-tetra-carb-oxy-lic dianhydride.
AB  - The title compound, C(10)H(8)O(6), a promising raw material to obtain colorless
      polyimides which are applied to microelectronic and optoelectronic devices,
      adopts a folded conformation in which the dihedral angle between the two anhydro
      rings is 55.15 (8) degrees . The central six-membered ring assumes a conformation
      inter-mediate between boat and twist-boat. In the crystal, mol-ecules are linked
      by weak C-H?O inter-actions, forming a layer parallel to the bc plane.

PMID- 22412497
TI  - 2-(Biphenyl-4-yl)propan-2-ol.
AB  - The title compound, C(15)H(16)O, crystallizes with two independent mol-ecules in
      the asymmetric unit. Due to the space-group symmetry, this results in the
      formation of a tetra-mer where the four mol-ecules are connected by O-H?O
      hydrogen bonds. The mol-ecules pack parallel to the c axis. Both mol-ecules in
      the asymmetric unit are nonplanar and the dihedral angles between connected
      aromatic rings in each mol-ecule are 7.96 (12) and 9.75 (13) degrees . This
      contrasts with the gas phase density functional theory (DFT) optimized
      conformation, where this dihedral angle is 39.33 degrees .

PMID- 22412498
TI  - Methyl N-({[2-(2-meth-oxy-acetamido)-4-(phenyl-sulfan-yl)phen-yl]amino}[(meth-oxy
      carbonyl)imino]methyl)carbamate.
AB  - In the title compound, C(20)H(22)N(4)O(6)S, the phenyl and benzene rings form a
      dihedral angle of 58.75 (5) degrees . Intra-molecular N-H?O and N-H?N hydrogen
      bonds generate two S(6) and one S(7) ring motif, respectively. In the crystal,
      mol-ecules are linked via N-H?O, N-H?N, C-H?S and C-H?O hydrogen bonds, forming
      two-dimensional networks parallel to the bc plane.

PMID- 22412499
TI  - 2-[3,5-Dioxo-4-(pyridin-3-yl)piperazin-1-yl]acetic acid.
AB  - In the title compound, C(11)H(11)N(3)O(4), the 3,5-dioxopiperazine ring adopts an
      envelope conformation, with the N atom connecting to the -CH(2)COOH group on the
      flap. In the crystal, mol-ecules are linked by O-H?N hydrogen bonds to produce a
      linear chain running along the c axis. pi-pi stacking is observed between
      parallel pyridine rings of adjacent mol-ecules, the centroid-centroid distance
      being 3.834 (2) A.

PMID- 22412500
TI  - 3-(4-Bromo-phenyl-sulfin-yl)-2,5-dimethyl-1-benzofuran.
AB  - In the title compound, C(16)H(13)BrO(2)S, the 4-bromo-phenyl ring makes a
      dihedral angle of 87.87 (6) degrees  with the mean plane of the benzofuran
      fragment. In the crystal, mol-ecules are linked by a weak pi-pi inter-action
      between the 4-bromo-phenyl rings [centroid-to-centroid distance = 3.907 (3) A,
      inter-planar distance = 3.528 (3) A and slippage = 1.679 (3) A].

PMID- 22412501
TI  - Ethyl 2-amino-4,6-bis-(4-fluoro-phen-yl)cyclo-hexa-1,3-diene-1-carboxyl-ate.
AB  - In the title compound, C(21)H(19)F(2)NO(2), the cyclo-hexa-1,3-diene ring is in a
      distorted envelope conformation. The dihedral angles between the mean planes of
      the diene moiety and the two fluoro-phenyl rings are 42.8 (2) and 75.0 (5)
      degrees . The two fluoro-phenyl rings are inclined to one another by 87.0 (3)
      degrees . In the crystal, intra-molecular N-H?O hydrogen bonds and weak N-H?O and
      N-H?F inter-molecular inter-actions are observed forming an infinite two
      dimensional network along [011].

PMID- 22412502
TI  - (1S,2R,6R,7aS)-1,2,6-Trihy-droxy-hexa-hydro-1H-pyrrolizin-3-one.
AB  - In the title compound, C(7)H(11)NO(4), prepared via a Morita-Baylis-Hillman
      adduct, the five-membered ring bearing three O atoms approximates to a twisted
      conformation, whereas the other ring is close to an envelope, with a C atom in
      the flap position. The dihedral angle between their mean planes (all atoms) is
      23.11 (9) degrees . The new stereocenters are created in a trans-diaxial
      configuration. In the crystal, O-H?O and O-H?(O,O) hydrogen bonds link the mol
      ecules, generating a three-dimensional network. A weak C-H?O inter-action also
      occurs.

PMID- 22412503
TI  - (1S,2S,6R,7aR)-2-Benzyl-1,6-dihy-droxy-hexa-hydro-pyrrolizin-3-one.
AB  - In the title compound, C(14)H(17)NO(3), the dihedral angles show that the H atoms
      at two stereocenters are in a trans-diaxial configuration. In the crystal, the
      molecules are linked by O-H?O hydrogen bonds. The absolute configuration of the
      molecule has been established on the basis of refinement of the Hooft and Flack
      parameters.

PMID- 22412504
TI  - Triclinic polymorph of bis-(triphenyl-sil-yl) oxide toluene disolvate.
AB  - A new polymorph of the title compound, C(36)H(30)OSi(2).2C(7)H(8), is reported,
      which is triclinic (P-1) instead of possessing the previously reported
      rhombohedral symmetry [Honle et al. (1990). Acta Cryst. C46, 1982-1984]. Each of
      the -SiPh(3) units are related by the inversion center. The Si-O-Si moiety is
      linear with the O atom sitting on an inversion center, and the O-Si-(toluene ring
      centroid) angle is 3.69 (15) degrees . Each toluene mol-ecule is 5.622 (2) A from
      the Si atom and has its closest contacts with the phenyl rings outside of the van
      der Waals radii.

PMID- 22412505
TI  - 9alpha-Hy-droxy-12-{[4-(4-meth-oxy-phen-yl)piperazin-1-yl]meth-yl}-4,8-dimethyl
      3,14-dioxatricyclo-[9.3.0.0]tetra-dec-7-en-13-one.
AB  - The title compound, C(26)H(36)N(2)O(5), was synthesized from 9alpha-hy-droxy
      parthenolide (9alpha-hy-droxy-4,8-dimethyl-12-methyl-ene-3,14-dioxatricyclo
      [9.3.0.0(2,4)]tetra-dec-7-en-13-one), wich was isolated from the chloro-form
      extract of the aerial parts of Anvillea radiata. The mol-ecule is built up from
      fused five- and ten-membered rings with the meth-oxy-phenyl-piperazine group as a
      substituent. The ten-membered ring adopts an approximate chair-chair
      conformation, while the piperazine ring displays a chair conformation and the
      five-membered ring a flattened envelope conformation; the C(H)-C-C(H) atoms
      representing the flap lie out of the mean plane through the remaining four atoms
      by 0.343 (3) A. The dihedral angle between the mean planes of the ten-membered
      ring and the lactone ring is 18.12 (14) degrees . An intra-molecular O-H?N
      hydrogen bond occurs. The crystal structure features weak C-H?O inter-actions.

PMID- 22412506
TI  - Nilutamide.
AB  - THE CRYSTAL STRUCTURE OF NILUTAMIDE [SYSTEMATIC NAME: 5,5-dimethyl-3-[4-nitro-3
      (trifluoro-meth-yl)phen-yl]imidazolidine-2,4-dione], C(12)H(10)F(3)N(3)O(4), was
      determined at 150 K. The dihedral angle between the mean planes through the
      imidazoline [maximum deviation = 0.0396 (14) A] and benzene rings is 51.49 (5)
      degrees . The mol-ecule exhibits inter-molecular hydrogen bonding via N-H?O inter
      actions, resulting in the formation of chains parallel to the c axis.

PMID- 22412507
TI  - N'-[3-(Hy-droxy-imino)-butan-2-yl-idene]-4-methyl-benzene-1-sulfono-hydrazide.
AB  - In the title compound, C(11)H(15)N(3)O(3)S, the C-S-N(H)-N linkage is nonplanar,
      the torsion angle being 75.70 (12) degrees . The compound has two almost planar
      fragments linked to the S atom: the hydrazone-derivative fragment [(HONC(4)H(6))N
      N(H)-] and the tolyl fragment (C(7)H(7)-) have maximum deviations from the mean
      plane through the non-H atoms of 0.0260 (10) and 0.0148 (14) A, respectively. The
      two planar fragments make an inter-planar angle of 79.47 (5) degrees . In the
      crystal, mol-ecules are connected through inversion centers via pairs of N-H?O
      and O-H?N hydrogen bonds.

PMID- 22412508
TI  - Methyl 6-amino-6-oxohexa-noate.
AB  - The title compound, C(7)H(13)NO(3), adopts an approximately planar conformation.
      The torsion angles in the aliphatic chain between the carbonyl group C atoms
      range from 172.97 (14) to 179.38 (14) degrees  and the r.m.s. deviation of all
      non-H atoms is 0.059 A. The crystal packing is dominated by two strong N-H?O
      hydrogen bonds involving the amide groups and forming R(2) (2)(8) rings and C(4)
      chains. Overall, a two-dimensional network parallel to (100) is formed. A weak
      inter-molecular C-H?O inter-action is also present.

PMID- 22412509
TI  - 3-Meth-oxy-3-oxopropanaminium chloride.
AB  - In the title compound, C(4)H(10)NO(2) (+).Cl(-), the central ethyl-ene bond of
      the cation adopts a gauche conformation. The three H atoms of the -NH(3) (+)
      group are engaged in strong and highly directional inter-molecular N-H?Cl
      hydrogen bonds, which result in a tape-like arrangement along [010] of the
      respective ion pairs. In addition, weak inter-molecular C-H?Cl and C-H?O inter
      actions are present.

PMID- 22412510
TI  - (E)-2-({2-[(E)-(Hy-droxy-imino)-meth-yl]phen-oxy}meth-yl)-3-phenyl-acrylonitrile.
AB  - In the title compound, C(17)H(14)N(2)O(2), the hy-droxy-ethanimine group adopts
      an anti-periplanar conformation. In the crystal, mol-ecules are linked by O-H?N
      hydrogen bonds, forming zigzag chains running along the c axis.

PMID- 22412511
TI  - 4,4'-Bipyridine-2-meth-oxy-benzoic acid (1/2).
AB  - The asymmetric unit of the title compound, C(10)H(8)N(2).2C(8)H(8)O(3), contains
      two 2-meth-oxy-benzoic acid mol-ecules and one 4,4'-bipyridine mol-ecule. The
      4,4'-bipyridine mol-ecule is disordered over two positions in a 1:1 ratio. In the
      crystal, the 2-meth-oxy-benzoic acid and 4,4'-bipyridine mol-ecules are connected
      by inter-molecular O-H?N hydrogen bonds. The dihedral angle between the carboxy
      group and its attached ring is 26.823 (2) degrees .

PMID- 22412512
TI  - 3,6-Bis(4-chloro-phen-yl)-N,N-bis-(1-phenyl-eth-yl)-1,2,4,5-tetra-zine-1,4-di
      carboxamide.
AB  - In the title mol-ecule, C(32)H(28)Cl(2)N(6)O(2), the amide-substituted N atoms of
      the tetra-zine ring deviate from the approximate plane of the four other atoms in
      the ring by 0.468 (3) and 0.484 (3) A, forming a boat conformation. The dihedral
      angle between the two phenyl rings is 67.0 (1) degrees  and that between the two
      chloro-substituted benzene rings is 73.8 (1) degrees . Two intra-molecular N-H?N
      hydrogen bonds are observed.

PMID- 22412513
TI  - Tramadolium picrate.
AB  - In the title salt {systematic name: [2-hy-droxy-3-(3-meth-oxy-phen-yl)cyclo-hexyl
      meth-yl]dimethyl-aza-nium 2,4,6-trinitro-phenol-ate}, C(16)H(26)NO(2)
      (+).C(6)H(2)N(3)O(7) (-), the cation is protonated at the N atom. The cyclo
      hexane ring adopts a chair conformation with the hy-droxy substituent in an axial
      position. In the crystal, O-H?O and N-H?O hydrogen bonds link the cations and
      anions into supra-molecular chains along [100].

PMID- 22412514
TI  - 4,5-Diphen-oxy-benzene-1,2-dicarbo-nitrile.
AB  - In the title compound, C(20)H(12)N(2)O(2), the phenyl and benzene rings are
      mutually perpendicular, with the dihedral angle between the phenyl rings being
      87.92 (16) degrees  and those formed between the phenyl rings and the benzene
      rings being 73.68 (15) and 84.65 (15) degrees . Helical supra-molecular chains
      along [010], mediated by C-H?N inter-actions, are found in the crystal structure.

PMID- 22412515
TI  - (E)-3-Methyl-N'-(4-nitro-benzyl-idene)benzohydrazide methanol monosolvate.
AB  - The title hydrazone compound, C(15)H(13)N(3)O(3).CH(3)OH, crystallized as a
      methanol solvate. The hydrazone mol-ecule has an E configuration about the C=N
      bond and is almost planar, with a dihedral angle between the benzene rings of 5.3
      (3) degrees . In the crystal, the hydrazone mol-ecules are linked via the
      methanol solvent mol-ecule through N-H?O and O-H?O hydrogen bonds, so forming
      chains propagating along the a-axis direction.

PMID- 22412516
TI  - (E)-N'-(2-Hy-droxy-3,5-diiodo-benzyl-idene)-3-methyl-benzohydrazide.
AB  - In the title compound, C(15)H(12)I(2)N(2)O(2), the dihedral angle between the
      benzene rings is 26.5 (3) degrees  and the mol-ecule has an E configuration about
      the C=N bond. An intra-molecular O-H?N hydrogen bond is observed in the mol
      ecule. In the crystal, mol-ecules are linked by N-H?O hydrogen bonds, forming
      chains along the c axis.

PMID- 22412517
TI  - (E)-1-{4-[Bis(4-bromo-phen-yl)meth-yl]piperazin-1-yl}-3-(4-eth-oxy-phen-yl)prop-2
      en-1-one.
AB  - In the title compound, C(28)H(28)Br(2)N(2)O(2), the C=C double bond has an E
      configuration and the piperazine ring has a chair conformation, with the N-C
      bonds in equatorial orientations. The dihedral angle between the bromo-benzene
      rings is 83.1 (4) degrees . In the crystal, mol-ecules are linked by C-H?O and C
      H?Br hydrogen bonds.

PMID- 22412518
TI  - (E)-1-{4-[Bis(4-bromo-phen-yl)meth-yl]piperazin-1-yl}-3-(4-methyl-phen-yl)prop-2
      en-1-one.
AB  - In the title compound, C(27)H(26)Br(2)N(2)O, the piperazine ring adopts a chair
      conformation with the N-C bonds in equatorial orientations. The C=C double bond
      has an E configuration. The dihedral angle between the bromo-benzene rings is
      83.0 (4) degrees . In the crystal, inversion dimers linked through pairs of C-H?O
      hydrogen bonds generate R(2) (2)(10) loops.

PMID- 22412520
TI  - (Z)-N-{(E)-10-[(2,6-Diisopropyl-phen-yl)-imino]-9,10-dihydro-phenanthren-9-yl
      idene}-2,6-dimethyl-aniline.
AB  - The title compound, C(34)H(34)N(2), adopts a Z,E configuration with respect to
      the N=C-C=N backbone, with an N-C-C-N torsion angle of 41.1 (4) degrees  The
      dihedral angle between the benzene rings in the 9,10-dihydro-phenanthrene moiety
      is 18.0 (1) degrees .

PMID- 22412519
TI  - Dimethyl 6-acetyl-2-methyl-1,2-dihydroquinoline-2,4-dicarboxyl-ate.
AB  - In the title compound, C(16)H(17)NO(5), the dihydro-pyridine ring adopts a sofa
      conformation. In the crystal, inter-molecular N-H?O hydrogen bonds link the mol
      ecules into chains running along the b axis.

PMID- 22412521
TI  - Methyl (E)-2-({2-[(E)-(hy-droxy-imino)-meth-yl]phen-oxy}meth-yl)-3-phenyl
      acrylate.
AB  - In the title compound, C(18)H(17)NO(4), the hy-droxy-ethanimine group is
      essentially coplanar with the ring to which it is attached [C-C-N-O torsion angle
      = 179.94 (14) degrees ]. The mol-ecules are linked into cyclic centrosymmetric
      R(2) (2)(6) dimers via O-H?N hydrogen bonds and the crystal packing is further
      stabilized by C-H?O inter-actions.

PMID- 22412522
TI  - 1-(2-Meth-oxy-phen-yl)-2-{[2-(2-meth-oxy-phen-yl)hydrazinyl-idene](nitro)-meth
      yl}diazene.
AB  - In the title compound, C(15)H(15)N(5)O(4), a nitro-formazan derivative, the
      formazan unit is essentially planar with an r.m.s. deviation of 0.0204 (6) A and
      adopts a closed syn,s-cis configuration with an intra-molecular N-H?N hydrogen
      bond. The formazan plane makes dihedral angles of 4.32 (5) and 24.35 (5) degrees 
      with the benzene rings. The dihedral angle between the formazan plane and the
      nitro group is 12.58 (8) degrees . In the crystal, C-H?O inter-actions connect
      the mol-ecules into an inversion dimer.

PMID- 22412523
TI  - Ergotaminine.
AB  - The title compound {systematic name: (6aR,9S)-N-[(2R,5S,10aS,10bS)-5-benzyl-10b
      hy-droxy-2-methyl-3,6-dioxoocta-hydro-8H-oxazolo[3,2-a]pyrrolo-[2,1-c]pyrazin-2
      yl]-7-methyl-4,6,6a,7,8,9-hexa-hydro-indolo[4,3-fg]quinoline-9-carboxamide},
      C(33)H(35)N(5)O(5), was formed by an epimerization reaction of ergotamine. The
      non-aromatic ring (ring C of the ergoline skeleton) directly fused to the
      aromatic rings is nearly planar [maximum deviation = 0.317 (4) A] and shows an
      envelope conformation, whereas ring D, involved in an intra-molecular N-H?N
      hydrogen bond exhibits a slightly distorted chair conformation. The structure
      displays chains running approximately parallel to the diagonal of bc plane that
      are formed through N-H?O hydrogen bonds.

PMID- 22412524
TI  - 5,6-Dimethyl-4-(thio-phen-2-yl)-1H-pyrazolo-[3,4-b]pyridin-3-amine.
AB  - In the title mol-ecule, C(12)H(12)N(4)S, the thio-phene ring is disordered over
      two orientations with a refined site-occupancy ratio of 0.777 (4):0.223 (4). The
      pyrazolo-pyridine ring system is essentially planar with an r.m.s. deviation of
      0.0069 (3) A and makes dihedral angles of 82.8 (2) and 72.6 (5) degrees ,
      respectively, with the major and minor components of the thio-phene ring. In the
      crystal, mol-ecules are linked into a chain along the a axis by a pair of N
      H?N(pyrazole) hydrogen bonds and a pair of N-H?N(pyridine) hydrogen bonds, both
      having a centrosymmetric R(2) (2)(8) graph-set motif. A C-H?pi inter-action is
      also present.

PMID- 22412525
TI  - 1,1'-(Phenyl-methyl-ene)dinaphthalen-2-ol.
AB  - In the title compound, C(27)H(20)O(2), the phenyl ring is oriented with respect
      to the naphthalene ring systems at 57.87 (6) and 85.12 (6) degrees . The two
      naphthalene ring systems make a dihedral angle of 70.10 (4) degrees . In the mol
      ecule, the hy-droxy groups are involved in a strong intra-molecular O-H?O
      hydrogen bond. In the crystal, inversion dimers linked by pairs of O-H?O hydrogen
      bonds occur. A weak C-H?pi inter-action is also observed in the crystal.

PMID- 22412526
TI  - (1H-Benzimidazol-1-yl)methanol.
AB  - In the title compound, C(8)H(8)N(2)O, the N-CH(2) and CH(2)-O bond lengths can be
      correlated to the manifestation of an anomeric effect in the N-CH(2)-O moiety. In
      the crystal, inter-molecular O-H?N hydrogen bonds link the mol-ecules into zigzag
      chains, with graph-set motif C(6), parallel to [001]. These chains are further
      linked into sheets by weak nonclassical C-H?O hydrogen bonds.

PMID- 22412527
TI  - (2E)-1-(2,4-Dichloro-phen-yl)-3-[3-(4-nitro-phen-yl)-1-phenyl-1H-pyrazol-4
      yl]prop-2-en-1-one.
AB  - In the title compound, C(24)H(15)Cl(2)N(3)O(3), the C=C double bond is E
      configured. The 1-phenyl-1H-pyrazole moiety is roughly planar (r.m.s. deviation
      of all fitted non-H atoms = 0.0780 A), but the mean planes of the two components
      are inclined at an angle of 9.95 (7) degrees . The mean plane defined by the non
      H atoms of the 1H-pyrazole ring encloses angles of 9.95 (7), 24.54 (6) and 43.02
      (6) degrees  with the mean planes of the different benzene rings. In the crystal,
      C-H?O contacts are present and result in the formation of a double-layer two
      dimensional network lying parallel to (110). The shortest inter-centroid distance
      between two aromatic systems is 3.5455 (7) A and is apparent between two pyrazole
      systems. Further pi-pi inter-actions are manifest between a pair of 4-nitro
      phenyl rings [centroid-to-centroid distance = 3.6443 (7) A] and a pair of 2,4
      dichloro-phenyl rings [centroid-to-centroid distance = 3.7797 (7) A].

PMID- 22412528
TI  - 2,2'-{[4,6-Bis(octyl-amino)-1,3,5-triazin-2-yl]aza-nedi-yl}diethanol.
AB  - In the title compound, C(23)H(46)N(6)O(2), the two hy-droxy groups are located on
      opposite sides of the triazine ring. One of the hy-droxy groups links with the
      triazine N atom via an intra-molecular O-H?N hydrogen bond. Inter-molecular O-H?N
      and N-H?O hydrogen bonding is observed in the crystal structure. pi-pi stacking
      is also observed between parallel triazine rings of adjacent mol-ecules, the
      centroid-centroid distance being 3.5944 (14) A.

PMID- 22412529
TI  - 3,3'-Dibenzoyl-1,1'-dibenzyl-1,1'-(ethane-1,2-di-yl)-dithio-urea.
AB  - In the title compound, C(32)H(30)N(4)O(2)S(2), the carbonyl and thio-carbonyl
      groups are found in a rare synclinal conformation, with an S-C?C-O pseudo-torsion
      angle of 62.6 (2) degrees . The mol-ecule has C(i) = S(2) point-group symmetry
      with a crystallographic center of inversion located in the middle of the ethyl
      ene bridge. One of the symmetry-independent phenyl rings is disordered over two
      orientations, with a site-occupation ratio of 70:30. The distances between the
      centroids of the nearest phenyl rings are equal to one of the lattice constants
      [a = 4.7767 (2) A], so stacking inter-actions are extremely weak. Mol-ecules are
      joined by bifurcated hydrogen bonds (N-H?O and N-H?S), forming a ladder-like
      arrangement along [100]. van der Waals forces combine these ladders into a three
      dimensional structure. The dependency between the S?O distance and the improper
      S=C?C=O torsion angle based on 739 structures containing the CC(=O)NC(=S)N moiety
      is discussed.

PMID- 22412530
TI  - 4-Hy-droxy-2-methyl-1,1-dioxo-2H-1lambda,2- benzothia-zine-3-carb-oxy-lic acid
      hemihydrate.
AB  - In the title compound, C(10)H(9)NO(5)S.0.5H(2)O, two geometrically different
      organic mol-ecules are present. The benzene rings and the carboxyl-ate groups are
      oriented at dihedral angles of 13.44 (4) and 21.15 (18) degrees . In both mol
      ecules, an intra-molecular O-H?O hydrogen bond generates an S(6) ring. In the
      crystal, both moleucles form inversion dimers linked by pairs of O-H?O hydrogen
      bonds to generate R(2) (2)(8) loops. The dimers are consolidated into chains
      extending along [100] by bridging O-H?O hydrogen bonds from the water mol-ecule.
      A weak C-H?O hydrogen bond also occurs.

PMID- 22412531
TI  - (E)-N-(1-Benzothio-phen-3-yl-methyl-idene)-2,6-dimethyl-aniline.
AB  - In the title compound, C(17)H(15)NS, the benzothio-phene residue and the
      substituted benzene ring are oriented at a dihedral angle of 61.99 (7) degrees .
      An inter-molecular C-H?pi inter-action contributes to the stability of the
      crystal structure.

PMID- 22412532
TI  - 9-(3-Fluoro-phen-oxy-carbon-yl)-10-methyl-acridinium trifluoro-methane-sulfonate
      monohydrate.
AB  - In the crystal structure of the title mol-ecular salt, C(21)H(15)FNO(2)
      (+).CF(3)SO(3) (-).H(2)O, the cations form inversion dimers through pi-pi inter
      actions between the acridine ring systems. These dimers are linked via C-H?O and
      C-F?pi inter-actions to adjacent anions, and by C-H?pi and C-F?pi inter-actions
      to neighbouring cations. The water mol-ecule links two sites of the cation by C
      H?O inter-actions and two adjacent anions by O-H?O hydrogen bonds. The mean
      planes of the acridine and benzene ring systems are oriented at a dihedral angle
      of 15.1 (1) degrees . The carboxyl group is twisted at an angle of 84.5 (1)
      degrees  relative to the acridine skeleton. The mean planes of the acridine ring
      systems are parallel in the crystal.

PMID- 22412533
TI  - (E)-N-[3-(Imidazol-1-yl)-1-phenyl-propyl-idene]hydroxyl-amine.
AB  - The title compound, C(12)H(13)N(3)O, exists in an E configuration with respect to
      the C=N bond [1.285 (2) A]. The imidazole ring forms a dihedral angle of 75.97
      (10) degrees  with the phenyl ring. In the crystal, mol-ecules are linked via O
      H?N and C-H?N hydrogen bonds into sheets lying parallel to (001). The crystal
      structure also features C-H?pi inter-actions.

PMID- 22412534
TI  - 3-(1H-Imidazol-1-yl)-1-phenyl-propan-1-ol.
AB  - In the title compound, C(12)H(14)N(2)O, the imidazole ring forms a dihedral angle
      of 66.73 (5) degrees  with the phenyl ring. In the crystal, mol-ecules are linked
      via O-H?N and C-H?O hydrogen bonds into sheets lying parallel to (100). The
      crystal structure is further consolidated by C-H?pi inter-actions.

PMID- 22412535
TI  - (E)-3-(4-Chloro-phen-yl)-1-(4-fluoro-phenyl)-prop-2-en-1-one.
AB  - In the title compound, C(15)H(10)ClFO, the fluoro-substituted benzene ring forms
      a dihedral angle of 44.41 (6) degrees  with the chloro-substituted benzene ring.
      The only significant directional bonds in the crystal are weak C-H?pi inter
      actions.

PMID- 22412536
TI  - Methyl 1-ethyl-7-methyl-4-oxo-1,4-di-hydro-1,8-naphthyridine-3-carboxyl-ate
      monohydrate.
AB  - In the structure of the title compound, C(13)H(14)N(2)O(3).H(2)O, all atoms of
      the organic molecule except the terminal methyl group of the ethyl group attached
      to the N atom of the pyridinone ring are roughly coplanar, with an r.m.s.
      deviation of 0.0897 A. In the crystal, C-H?O contacts link pairs of naphthyridine
      mol-ecules into head-to-tail dimers. These are joined by strong O-H?O hydrogen
      bonds from the water molecules into infinite chains along the a axis.

PMID- 22412537
TI  - 4-(4-Fluoro-phen-yl)-1-phenyl-3-(pyridin-4-yl)-1H-pyrazol-5-amine.
AB  - In the title compound, C(20)H(15)FN(4), the pyrazole ring forms dihedral angles
      of 43.51 (6), 39.95 (6) and 32.23 (6) degrees  with the directly attached 4
      fluoro-phenyl, pyridine and phenyl rings, respectively. The crystal packing is
      stabilized by inter-molecular N-H?N and N-H?F hydrogen bonds.

PMID- 22412538
TI  - 4-(4-Fluoro-phen-yl)-1-(4-nitro-phen-yl)-3-(pyridin-4-yl)-1H-pyrazol-5-amine.
AB  - In the crystal structure of the title compound, C(20)H(14)FN(5)O(2), the pyrazole
      ring forms dihedral angles of 59.3 (2), 25.6 (2) and 46.0 (2) degrees  with the
      directly attached 4-fluoro-phenyl, pyridine and nitro-phenyl rings, respectively.
      The crystal packing is characterized by inter-molecular N-H?N and N-H?O hydrogen
      bonds.

PMID- 22412539
TI  - (E)-1-(1,3-Benzodioxol-5-yl)-4,4-di-methyl-pent-1-en-3-one.
AB  - In the mol-ecule of the title compound, C(14)H(16)O(3), all non-H atoms except
      for one methyl C atom lie on a crystallographic mirror plane. The conformation
      with respect to the C=C bond [1.3465 (12) A] is trans. In the crystal, mol-ecules
      are linked via C-H?O hydrogen bonds into C(5) chains propagating along [100].

PMID- 22412540
TI  - 1,3-Dioxo-2,3-dihydro-1H-isoindol-2-yl 2,3,4-tri-O-acetyl-beta-d-xyloside.
AB  - The title compound, C(19)H(19)NO(10), was obtained from the reaction of alpha-d-1
      bromo-2,3,4-tri-O-acetylxylose with N-hy-droxy-phthalimide in the presence of
      potassium carbonate. The asymmetric unit contains two independent mol-ecules, in
      which the O-CH-O-N torsion angles are 73.0 (4) and 65.0 (4) degrees . The hexa
      pyranosyl rings adopt chair conformations and the substituent groups are in
      equatorial positions. In the crystal, mol-ecules are linked by nonclassical C-H?O
      hydrogen bonds.

PMID- 22412541
TI  - (E)-3-(1,3-Benzodioxol-5-yl)-1-{4-[bis-(4-meth-oxy-phen-yl)meth-yl]piperazin-1
      yl}prop-2-en-1-one.
AB  - There are two crystallographically independent mol-ecules in the asymmetric unit
      of the title compound, C(29)H(30)N(2)O(5), each having an E conformation about
      the C=C double bond. The dihedral angles between the meth-oxy-benzene rings in
      the two mol-ecules are 71.39 (17) and 68.64 (17) degrees . In the crystal, mol
      ecules are linked by C-H?O inter-actions.

PMID- 22412542
TI  - 1-Ethenyl-4-[(phenylsulfanyl)methyl]-benzene.
AB  - The dihedral angle between the aromatic rings in the title compound, C(15)H(14)S,
      is 72.38 (7) degrees . In the crystal, the mol-ecules are connected by C-H?pi
      inter-actions.

PMID- 22412543
TI  - (6Z)-3,5-Bis(4-fluoro-phen-yl)-6-(1-hy-droxy-ethyl-idene)cyclo-hex-2-en-1-one.
AB  - In the title compound, C(20)H(16)F(2)O(2), the cyclo-hex-2-en-1-one ring adopts a
      distorted envelope conformation and the dihedral angles between its six-atom mean
      plane and the fluorophenyl rings are 38.9(8) and 82.3(1) degrees . The two fluoro
      phenyl rings are oriented at an angle of 77.3 (3) degrees . The long hy-droxy O-H
      bond length of 1.22 (3) and the H?O distance of 1.28 (3) A, together with a
      longer than expected C=O bond length [1.290 (2) A] in the hy-droxy(en-1-one)
      group, indicate sharing of the H atom as O?H?O between the two O atoms and the
      influence of electron delocalization. Weak C-H?O inter-molecular inter-actions
      form an infinite two-dimensional network in (011).

PMID- 22412544
TI  - Trimethyl-sulfonium 1-amino-6-fluoro-2,3,4,5,7,8,9,10,11,12-decaiodo-1-carba
      closo-dodeca-borate.
AB  - In the asymmetric unit of the title salt, C(3)H(9)S(+).CH(2)B(11)FI(10)N(-) or
      (CH(3))(3)S[1-H(2)N-6-F-closo-1-CB(11)I(10)], both ions lie in general positions.
      The anion is perfectly ordered and so the positions of the C-NH(2) vertex and the
      fluorine substituent are clearly assigned. The relatively short C-N bond length
      may be inter-preted in terms of a very electron deficient {closo-1-CB(11)}
      cluster.

PMID- 22412545
TI  - 4-Methyl-2-oxo-2H-chromen-7-yl 4-fluoro-benzene-sulfonate.
AB  - In the asymmetric unit of the title compound, C(16)H(11)FO(5)S, the 2H-chromene
      ring is essentially planar, with a maximum deviation of 0.040 (2) A. The dihedral
      angle between the 2H-chromene ring and the 4-fluoro-phenyl ring is 2.17 (8)
      degrees . One of the sulfonamide O atoms is approximately coplanar with the
      benzene ring [C-C-S-O torsion angle = 166.00 (14) degrees ], whereas the other O
      atom lies well below the plane [C-C-S-O = -61.35 (17) degrees ]. In the crystal,
      mol-ecules are connected by weak C-H?O hydrogen bonds, forming two-dimensional
      networks parallel to the ac plane.

PMID- 22412546
TI  - (1E,2E)-1,2-Bis[1-(3-nitro-phen-yl)ethyl-idene]hydrazine.
AB  - The asymmetric unit of the title compound, C(16)H(14)N(4)O(4), contains one half
      mol-ecule of (nitro-phen-yl)ethanimine and the complete mol-ecule is generated by
      a crystallographic inversion centre. The mol-ecule has an E conformation with
      respect to each C=N double bond. The central C=N-N=C plane is twisted from the
      benzene rings with a dihedral angle of 24.76 (11) degrees . In the crystal, C-H?O
      inter-actions link the molecules to form sheets that lie parallel to (10-4).

PMID- 22412547
TI  - {5-Chloro-2-[(4-chloro-benzyl-idene)-amino]-phen-yl}(phen-yl)methanone.
AB  - In the title compound, C(20)H(13)Cl(2)NO, the C=N bond adopts an E conformation.
      The chloro-substituted rings form a dihedral angle of 11.99 (9) degrees  with
      each other and form dihedral angles of 74.95 (9) and 83.26 (10) degrees  with the
      unsubstituted ring. In the crystal, mol-ecules are connected into dimers by pairs
      of weak C-H?O hydrogen bonds and the dimers are arranged in columns parallel to
      the a axis.

PMID- 22412548
TI  - {2-[(3-Bromo-benzyl-idene)amino]-5-chloro-phen-yl}(phen-yl)methanone.
AB  - In the title compound, C(20)H(13)BrClNO, the azomethine double bond [C=N = 1.246
      (4) A] adopts an E conformation. The bromo- and chlorophenyl rings are inclined
      to one another by 13.70 (11) degrees , and form dihedral angles of 76.68 (10) and
      74.24 (7) degrees , respectively, with the phenyl ring. In the crystal, mol
      ecules are linked by C-H?O hydrogen bonds to form double stranded chains
      propagating along the b-axis direction.

PMID- 22412549
TI  - rac-3-[(3-Chloro-anilino)(4-chloro-phenyl)meth-yl]thian-4-one.
AB  - In the title compound, C(18)H(17)Cl(2)NOS, the thio-pyran-one ring adopts a chair
      conformation, with the substituent in the axial position. The dihedral angle
      between the two benzene rings is 89.43 (1) degrees . In the crystal, mol-ecules
      form inversion dimers through inter-molecular N-H?O hydrogen bonds [graph set
      R(2) (2)(8)].

PMID- 22412550
TI  - 4-Meth-oxy-N-methyl-benzamide.
AB  - In the title compound, C(9)H(11)NO(2), the dihedral angle between the amide group
      and the benzene ring is 10.6 (1) degrees . In the crystal, mol-ecules are
      connected via N-H?O hydrogen bonds, supported by a C-H?O contact, forming chains
      along b. These chains are linked by C-H?pi inter-actions to give a three
      dimensional network.

PMID- 22412551
TI  - Dicyclo-hex-yl(4-isopropyl-phen-yl)phosphane selenide.
AB  - In the title compund, C(21)H(33)PSe, the Se=P bond is part of a distorted tetra
      hedral environment on the P atom. Both cyclo-hexyl groups adopt chair
      conformations. A cone angle of 170 degrees  was calculated using an adaptation of
      the Tolman model. Inter-molecular C-H?Se and C-H?Cg contacts are observed (Cg is
      the centroid of the benzene ring).

PMID- 22412552
TI  - 10-Ethyl-3-(5-methyl-1,3,4-oxadiazol-2-yl)-10H-phenothia-zine.
AB  - In the title compound, C(17)H(15)N(3)OS, the phenothia-zine ring system is
      slightly bent, with a dihedral angle of 13.68 (7) degrees  between the benzene
      rings. The dihedral angle between the oxadiazole ring and the adjacent benzene
      ring is 7.72 (7) degrees . In the crystal, a pi-pi inter-action with a centroid
      centroid distance of 3.752 (2) A is observed between the benzene rings of
      neighbouring mol-ecules.

PMID- 22412553
TI  - Isopropyl 3,4,5-trihy-droxy-benzoate.
AB  - In the title compound, C(10)H(12)O(5), the dihedral angle between the benzene
      ring is almost coplanar with the attached C(O)-O-C group [dihedral angle = 0.32
      (15) degrees ]. In the crystal, two intermolecular O-H?O hydrogen bonds make R(4)
      (4)(26) ring mofits.

PMID- 22412554
TI  - Triethyl-ammonium (2R,3R)-2,3-bis-(benzo-yloxy)-3-carb-oxy-propano-ate.
AB  - In the anion of the title salt, C(6)H(16)N(+).C(18)H(13)O(8) (-), one of the
      carboxyl groups is deprotonated. Its O atoms are involved in inter-molecular
      hydrogen bonding with the carboxyl group of an adjacent anion and the amino group
      of an adjacent cation. The two benzoyloxy rings are oriented with respect to each
      other at a dihedral angle of 79.46 (6) degrees .

PMID- 22412555
TI  - (3-Ethyl-6,7-dimeth-oxy-naphthalen-1-yl)(phen-yl)methanone.
AB  - The asymetric unit of the title mol-ecule, C(21)H(20)O(3), contains two
      crystallographically independent mol-ecules, A and B, which differ in the
      orientation of the ethyl group substituted on the naphthalene system; the
      dihedral angles between the ethyl group and the naphthalene system are 7.4 (3)
      and 68.1 (3) degrees , respectively, for mol-ecules A and B. The dihedral angles
      between the benzoyl and naphthalene groups are 64.7 (7) and 69.4 (8) degrees ,
      respectively, for mol-ecules A and B. The crystal structure features four
      aromatic pi-pi stacking interactions [centroid-centroid distances = 4.181 (1),
      3.891 (1), 4.423 (1) and 4.249 (1) A].

PMID- 22412556
TI  - N-[(Methyl-sulfan-yl)meth-yl]benzamide.
AB  - In the title compound, C(9)H(11)NOS, the phenyl ring and formamide unit make a
      dihedral angle of 23.93 (14) degrees , whereas the (methyl-sulfan-yl)methyl group
      is oriented at a dihedral angle of 61.31 (8) degrees  with respect to the phenyl
      ring. There are inter-molecular N-H?O hydrogen bonds, forming C(4) chains along
      the [010] direction. These polymeric chains are linked by C-H?O hydrogen bonds to
      form polymeric sheets in the (110) plane.

PMID- 22412557
TI  - (E)-4-Hy-droxy-N'-(2-hy-droxy-3,5-diiodo-benzyl-idene)-3-meth-oxy-benzohydrazide
      methanol monosolvate.
AB  - In the title compound, C(15)H(12)I(2)N(2)O(4).CH(3)OH, the hydrazone mol-ecule
      exists in an E conformation with respect to the C=N bond. The dihedral angle
      between the rings is 11.9 (2) degrees . There is one intra-molecular O-H?N
      hydrogen bond in the hydrazone mol-ecule. In the crystal, the hydrazone and
      methanol mol-ecules are linked through O-H?O and N-H?O hydrogen bonds and C-H?O
      inter-actions to form two-dimensional networks lying parallel to (001).

PMID- 22412558
TI  - (E)-4-Nitro-N'-(3-nitro-benzyl-idene)benzohydrazide.
AB  - The title compound, C(14)H(10)N(4)O(5), has an E conformation with respect to the
      C=N bond. The dihedral angle between the benzene rings is 2.41 (14) degrees . In
      the crystal, mol-ecules are linked through N-H?O hydrogen bonds to form chains
      along the c axis. C-H?O inter-actions are also present, linking the chains to
      form a three-dimensional network.

PMID- 22412559
TI  - 3-(Adamantan-1-yl)-4-(prop-2-en-1-yl)-1H-1,2,4-triazole-5(4H)-thione.
AB  - The title mol-ecule, C(15)H(21)N(3)S, exists as the thione tautomer in the solid
      state. The 1,2,4-triazole ring is almost planar (r.m.s. deviation = 0.004 A) and
      the prop-2-en-1-yl chain is close to being perpendicular to this plane [C-N-C-C
      torsion angle = 77.1 (5) degrees ]. In the crystal, centrosymmetric dimeric
      aggregates are formed by pairs of N-H?S hydrogen bonds as parts of eight-membered
      (?HNCS)(2) synthons. These are connected into layers parallel to (101) via C-H?pi
      inter-actions, where the pi-system is the triazole ring. The investigated sample
      was a nonmerohedral twin; the refined domain ratio was 0.655 (4):0.345 (4).

PMID- 22412560
TI  - 3-(Adamantan-1-yl)-1-[(4-ethyl-piperazin-1-yl)meth-yl]-4-[(E)-(4-hy-droxy-benzyl
      idene)amino]-1H-1,2,4-triazole-5(4H)-thione.
AB  - In the title thione, C(26)H(36)N(6)OS, the 1,2,4-triazole ring is planar (r.m.s.
      deviation = 0.020 A) and the benzene ring is twisted out of this plane [dihedral
      angle = 62.35 (12) degrees ]. Supra-molecular zigzag chains feature in the
      crystal packing. These are sustained by O-H?N(piperazine) hydrogen bonds, and are
      connected into the three-dimensional crystal structure by C-H?S and C-H?O inter
      actions. The crystal studied was a racemic twin.

PMID- 22412561
TI  - 1,1,3,3-Tetra-ethyl-isoindolin-2-ium chloride.
AB  - In the title compound, C(16)H(26)N(+).Cl(-), the cations and anions form discrete
      centrosymetric cyclic dimers through N-H?Cl hydrogen-bonding associations with
      graph-set R(4) (2)(8).

PMID- 22412562
TI  - rac-4-Carbamoylpiperidinium cis-2-car-boxy-cyclo-hexane-1-carboxyl-ate.
AB  - In the title racemic salt, C(6)H(13)N(2)O(+).C(8)H(11)O(4) (-), formed from the
      reaction of cis-cyclo-hexane-1,2-dicarb-oxy-lic anhydride with isonipecotamide,
      the cations are linked into duplex chain substructures through both
      centrosymmetric cyclic head-to-head 'amide motif' hydrogen-bonding associations
      [graph set R(2) (2)(8)] and 'side-by-side' R(2) (2)(14) associations. The anions
      are incorporated into the chains through cyclic R(4) (3)(10) inter-actions
      involving amide and piperidinium N-H?O(carbox-yl) hydrogen bonds which, together
      with inter-anion carb-oxy-lic acid O-H?O(carbox-yl) hydrogen bonds, give a two
      dimensional layered structure extending along (011).

PMID- 22412563
TI  - 1,2-Bis[(3,6,9-trimethyl-3,12-ep-oxy-3,4,5,5a,6,7,8,8a,9,10,12,12a-dodeca-hydro
      pyrano[4,3-j][1,2]benzodioxepin-4-yl)-oxy]ethane.
AB  - The title compound, C(32)H(50)O(10), prepared from a mixture of alpha- and beta
      dihydro-artemisinin, has two beta-arteether moieties linked via an -OCH(2)CH(2)O-
      bridge, so that the mol-ecule is symmetric about the bridge. Each asymmetric unit
      contains a beta-arteether moiety and an -OCH(2) group, which is only one-half of
      the mol-ecule. The endo-peroxide bridges of the parent compounds have been
      retained in each half of the diol-bridged dimer. The rings exhibit chair and
      twist-boat conformations.

PMID- 22412564
TI  - (6S,7S,8S,8aS)-6-Ethyl-3-oxo-1,2,3,5,6,7,8,8a-octa-hydro-indolizine-7,8-diyl
      diacetate.
AB  - In the mol-ecular structure of the title compound, C(14)H(21)NO(5), the six
      membered ring of the indolizine moiety adopts a chair conformation. There are two
      independent mol-ecules in the asymmetric unit. The oxopyrrolidine ring attached
      to the indolizine ring system is nearly planar, with mean deviations of 0.018 (3)
      and 0.010 (3) A for the two mol-ecules. The absolute configuration of the title
      compound was assigned from the synthesis.

PMID- 22412565
TI  - 2-(2,4,5-Trimeth-oxy-phen-yl)-2,3-dihydro-quinolin-4(1H)-one.
AB  - In the title aza-flavanone, C(18)H(19)NO(4), an intra-molecular cyclization
      product of chalcone, the central heterocyclic ring is in an envelope conformation
      and the dihedral angle between the benzene rings is 51.03 (10) degrees . The meth
      oxy groups at the ortho and para positions are slightly twisted from the benzene
      ring to which they are bound [C-O-C-C = 21.9 (3) and -171.93 (18) degrees ,
      respectively], whereas the meth-oxy group at the meta position is almost coplanar
      [C-O-C-C = 3.5 (3) degrees ]. In the crystal, mol-ecules are linked by N-H?O
      hydrogen bonds and weak C-H?O inter-actions into chains along the [001]
      direction. Weak C-H?pi inter-actions also occur.

PMID- 22412566
TI  - Methyl 4-{[(4-methyl-phen-yl)sulfon-yl]amino}-benzoate.
AB  - In the mol-ecule of the title compound, C(15)H(15)NO(4)S, the dihedral angle
      between the two rings is 88.05 (7) degrees . The methyl ester group is nearly
      coplanar with the adjacent ring [dihedral angle = 2.81 (10) degrees ], whereas it
      is oriented at 86.90 (9) degrees  with respect to the plane of the ring attached
      to the -SO(2)- group. Weak intra-molecular C-H?O hydrogen bonding completes S(5)
      and S(6) ring motifs. The mol-ecules form one-dimensional polymeric C(8) chains
      along the [010] direction due to N-H?O hydrogen bonding and these chains are
      linked by C-H?O hydrogen bonds, forming a three-dimensional network.

PMID- 22412567
TI  - Clarithromycin monohydrate: a synchrotron X-ray powder study.
AB  - In the crystal structure of the title compound, clarithromycin (CAM) monohydrate,
      C(38)H(69)NO(13).H(2)O, the water mol-ecule behaves as a proton donor and is
      hydrogen bonded to the hy-droxy O atom of the CAM cladinose ring. The hy-droxy O
      atom also behaves as a proton donor, forming an inter-molecular hydrogen bond
      with one of the hy-droxy groups of the 14-membered aglycone ring. The CAM mol
      ecules are linked through these hydrogen bonds into chains running parallel to
      the c axis.

PMID- 22412568
TI  - 4-[(4-Amino-phen-yl)sulfon-yl]aniline-3,5-dinitro-benzoic acid (1/1).
AB  - The title compound, C(7)H(4)N(2)O(6).C(12)H(12)N(2)O(2)S, is a 1:1 cocrystal of
      the drug dapsone with 3,5-dinitro-benzoic acid. The dihedral angle between the
      two aromatic rings of the dapsone mol-ecule is 75.4 (2) degrees , and the
      dihedral angles between these rings and that of the 3,5-dinitro-benzoic acid are
      64.5 (2) and 68.4 (2) degrees . A strong inter-molecular carb-oxy-lic acid O
      H?N(amine) hydrogen bond is found, together with inter-molecular amine N-H?O
      hydrogen-bonding associations with carboxyl, nitro and sulfone O-atom acceptors.
      In addition, weak pi-pi inter-actions between one of the dapsone benzene rings
      and the 3,5-dinitro-benzoic acid ring [ring centroid separation = 3.774 (2) A]
      results in a two-dimensional network structure.

PMID- 22412569
TI  - (Z)-4-(3-Fluoro-phen-yl)-1-(5-nitro-2-oxo-indolin-3-yl-idene)thio-semicarbazide.
AB  - In the title compound, C(15)H(10)FN(5)O(3)S, an intra-molecular N-H?N hydrogen
      bond generates an S(5) ring, whereas N-H?O and C-H?S inter-actions complete S(6)
      ring motifs. The dihedral angle between the isatin ring system and the fluoro
      benzene ring is 5.96 (6) degrees  and the complete mol-ecule is close to planar
      (r.m.s. deviation for all the non-H atoms = 0.112 A). In the crystal, mol-ecules
      are linked by N-H?O hydrogen bonds to form C(8) chains along the [100] direction
      and C-H?O inter-actions are also observed.

PMID- 22412570
TI  - N-Phenyl-2-(propan-2-yl-idene)-hydrazine-carboxamide.
AB  - In the title compound, C(10)H(13)N(3)O, the hydrazinecarboxamide N-N-C(=O)-N unit
      is nearly planar [maximum deviation = 0.018 (2) A] and is inclined at a dihedral
      angle of 8.45 (10) degrees  with respect to the plane of the phenyl ring. The mol
      ecular structure is stabilized by an intra-molecular C-H?O hydrogen bond which
      generates an S(6) ring motif. In the crystal, mol-ecules are linked into an
      inversion dimer by pairs of N-H?O and C-H?O hydrogen bonds.

PMID- 22412571
TI  - 14-Angeloyloxycacalohastine from Psacalium peltatum.
AB  - THE TITLE COMPOUND [SYSTEMATIC NAME: (9-meth-oxy-3,5-dimethyl-5,6-dihydro-naphtho
      [2,3-b]furan-4-yl)methyl 2-meth-yl-but-2-enoate], C(21)H(24)O(4), was isolated
      from matarique, or Psacalium peltatum (Kunth). The structure is almost planar.
      The angelo-yloxy group makes an angle of 62.08 (2) degrees  with the furan
      oeremophilane skeleton. The carbonyl O atom is disordered between two positions
      with a 76:24 ratio. The mol-ecules in the crystal are joined by very weak C-H-O
      inter-actions in the ac plane.

PMID- 22412572
TI  - Ethyl ({5-[5'-(2-eth-oxy-2-oxoeth-oxy)-4,4''-difluoro-1,1':3',1''-terphenyl-4'
      yl]-1,3,4-oxadiazol-2-yl}sulfan-yl)acetate.
AB  - In the title compound, C(28)H(24)F(2)N(2)O(6)S, the whole mol-ecule is disordered
      over two sites with refined occupancies of 0.778 (3) and 0.222 (3). The central
      benzene ring makes dihedral angles of 56.0 (4), 34.5 (4) and 70.9 (4) degrees ,
      respectively, with the two terminal benzene rings and the 1,3,4-oxadiazole ring
      in the major component of the disordered mol-ecule. The corresponding angles in
      the minor component are 59.7 (16), 25.6 (13) and 75.5 (14) degrees . In the
      crystal, mol-ecules are linked via C-H?F, C-H?N, C-H?O and C-H?S hydrogen bonds
      into a three-dimensional network. In addition, C-H?pi inter-actions are observed.

PMID- 22412573
TI  - 6-(2-Methyl-prop-yl)-4-oxo-2-sulfanyl-idene-1,2,3,4-tetra-hydro-pyrimidine-5
      carbonitrile.
AB  - The title thio-uracil derivative, C(9)H(11)N(3)OS, exists in the thione form. The
      six atoms comprising the ring are almost coplanar [r.m.s. deviation = 0.015 A]
      and the 2-methyl-propyl group lies approximately perpendicular to this plane [the
      N-C-C-C torsion angle is 72.88 (14) degrees ]. Linear supra-molecular chains
      along [001] sustained by N-H?O and N-H?S hydrogen bonding feature in the crystal
      packing.

PMID- 22412574
TI  - 2-Chloro-4-{(E)-[(4-chloro-phen-yl)imino]-meth-yl}phenol.
AB  - In the title Schiff base compound, C(13)H(9)Cl(2)NO, the dihedral angle between
      the mean planes of the benzene rings is 10.20 (10) degrees . The crystal
      structure is stabilized by O-H?N hydrogen bonds and weak pi-pi stacking inter
      actions [centroid-centroid distance = 3.757 (1) A].

PMID- 22412575
TI  - N'-(2-Hy-droxy-4-meth-oxy-benzyl-idene)-4-methyl-benzohydrazide.
AB  - The asymmetric unit of the title compound, C(16)H(16)N(2)O(3), contains four
      independent mol-ecules with different conformations; the dihedral angles between
      the two benzene rings in the mol-ecules are 39.7 (3), 45.4 (3), 50.6 (3) and 51.6
      (3) degrees . Intramolecular O-H?N hydrogen bonds are observed in the molecule.
      In the crystal, N-H?O hydrogen bonds link the mol-ecules into two
      crystallographically independent chains propagating in [010], and each chain is
      formed by two alternating independent mol-ecules. Weak C-H?O inter-actions also
      occur.

PMID- 22412576
TI  - (3,6-Dimethyl-1,2,4,5-tetra-zine-1,4-di-yl)bis-[(morpholin-4-yl)methanone].
AB  - In the title mol-ecule, C(14)H(22)N(6)O(4), the amide-substituted N atoms of the
      tetra-zine ring deviate from the approximate plane of the four other atoms in the
      ring by 0.160 (2) and 0.243 (2) A, forming a slight boat conformation. The
      morpholine rings are in chair conformations.

PMID- 22412577
TI  - Secohellebrigeninamide.
AB  - The title compound, C(26)H(37)NO(5), was the reaction product of hellebrigenin
      with N,N-dimethyl-formamide. It consists of three cyclo-hexane rings (A, B and
      C), one five-membered ring (D) and one dihydro-pyran ring (E). The
      stereochemistry of the ring junctions is is A/B cis, B/C trans, C/D cis and C/E
      trans. The cyclo-hexane rings A, B and C have chair conformations. Both the five
      membered ring D and the dihydro-pyran ring adopt an envelope conformation. Two
      orientations are found for the aldehyde group with occupancies of 0.608 (10) and
      0.392 (10). In the crystal, short O-H?O hydrogen bonds and short C-H?O contacts
      involving the hy-droxy group, terminal methyl group and carbonyl group link the
      mol-ecules into a three-dimensional network.

PMID- 22412578
TI  - (E)-3-Phenyl-2-(1-tosyl-1H-indol-3-ylcarbon-yl)acrylonitrile.
AB  - In the title compound, C(25)H(18)N(2)O(3)S, the indole moiety is planar and makes
      a dihedral angle of 89.95 (09) degrees  with the phenyl ring of the sulfonyl
      substituent. The mol-ecular conformation features a weak C-H?N short contact and
      the crystal packing reveals a weak C-H?O hydrogen bond.

PMID- 22412579
TI  - 2-{(E)-1-[2-(4-Nitro-phen-yl)hydrazin-1-yl-idene]eth-yl}benzene-1,3-diol.
AB  - The title compound, C(14)H(13)N(3)O(4), is close to planar, the dihedral angle
      between the terminal benzene rings being 5.80 (16) degrees ; the nitro group is
      coplanar with the benzene ring to which it is bonded [O-N-C-C torsion angle = 
      177.3 (3) degrees ]. The hy-droxy group forms an intra-molecular hydrogen bond
      with the imine N atom, and the conformation about the imine bond is E. In the
      crystal, layers in the (101) plane with an undulating topology are formed by O
      H?O and N-H?O hydrogen bonds along with C-H?O inter-actions. Centrosymmetrically
      related layers are connected via pi-pi inter-actions [ring centroid-centroid
      distance = 3.5739 (19) A] into double layers.

PMID- 22412580
TI  - 2,3-Dihydro-1H-cyclo-penta-[b]naph-tha-len-1-ol.
AB  - In the title compound, C(13)H(12)O, the cyclo-pentene ring fused with the
      naphthalene group adopts an envelope conformation. The cyclo-pentene torsion
      angle, with the fusion bond at the centre, has a magnitude of 1.16 (16) degrees .
      In the crystal, neigh-bouring mol-ecules are connected through O-H?O hydrogen
      bonds into an R(4) (4)(8) ring motif. The crystal packing also features weak pi
      pi stacking inter-actions [centroid-centroid distance = 3.8981 (8) A] and C-H?pi
      inter-actions.

PMID- 22412581
TI  - (E)-2,3-Bis[(E)-benzyl-idene-amino]-but-2-enedinitrile.
AB  - The asymmetric unit of the title compound, C(18)H(12)N(4), consists of a half-mol
      ecule, where the two halves of the mol-ecule are related by inversion symmetry.
      The mol-ecule is effectively planar, with the largest deviation from the 22-atom
      mean plane, measuring 0.024 (2) A, exhibited by the ortho-C atom of the phenyl
      ring. The crystal structure exhibits pi-stacking, with an inter-planar spacing of
      3.431 (3) A.

PMID- 22412582
TI  - 1,4-Bis(thio-phen-2-yl)butane-1,4-dione.
AB  - In the centrosymmetric title compound, C(12)H(10)O(2)S(2), the alkyl chains adopt
      a fully extended all-trans conformation with respect to the C(thio-phene)-C bond.
      The non-H atoms of the mol-ecule are nearly planar, with a maximum deviation of
      0.063 (2) A from the mean plane of the constituent atoms. In the crystal,
      symmetry-related mol-ecules are linked via pairs of C-H?pi contacts [H-centroid
      distances of the thio-phene units = 2.79 (9) and 2.82 (4) A], in turn inter
      digitating with each other along the bc plane, thus leading to an inter-woven two
      dimensional network.

PMID- 22412583
TI  - 1-(6-Chloro-1,3-benzothia-zol-2-yl)hydrazine.
AB  - The asymmetric unit of the title compound, C(7)H(6)ClN(3)S, consists of two
      crystallographically independent mol-ecules (A and B). The dihedral angle between
      the benzothia-zole ring system and the hydrazine group is 8.71 (6) degrees  in
      mol-ecule A and 7.16 (6) degrees  in mol-ecule B. The N-N-C-N and N-N-C-S torsion
      angles involving the hydrazine group are 170.89 (9) and -9.96 (13) degrees ,
      respectively, in mol-ecule A and 172.50 (9) and -7.43 (13) degrees ,
      respectively, in mol-ecule B. In the crystal, neighbouring mol-ecules are
      connected via pairs of N-H?N hydrogen bonds, generating R(2) (2)(8) ring motifs,
      and are connected further by N-H?N hydrogen bonds into sheets lying parallel to
      the ab plane. The crystal studied was an inversion twin, the refined ratio of the
      twin components being 0.50 (3):0.50 (3).

PMID- 22412584
TI  - 4-Methyl-N-{4-[(5-methyl-1,2-oxazol-3-yl)sulfamo-yl]phen-yl}benzene-sulfonamide.
AB  - In the title compound, C(17)H(17)N(3)O(5)S(2), the dihedral angle between the two
      benzene rings is 81.27 (8) degrees  and the heterocyclic ring is oriented at 9.1
      (2) and 76.01 (9) degrees  with respect to these rings. Mol-ecules are connected
      via N-H?N and N-H?O hydrogen bonds, generating an R(2) (2)(8) motif, into chains
      running along the [001] direction. There is also an intra-molecular C-H?O
      hydrogen bond completing an S(6) ring motif. The polymeric chains are inter
      linked through inter-molecular C-H?O hydrogen bonds.

PMID- 22412585
TI  - 1,2,3-Trimeth-oxy-4,5,6-trinitro-benzene.
AB  - In the title mol-ecule, C(9)H(9)N(3)O(9), the three neighbouring nitro groups are
      tilted with respect to the benzene mean plane by 75.8 (1), 27.7 (1) and 68.1 (1)
      degrees . The methyl C atoms of the three neighbouring meth-oxy groups deviate
      from this plane by 0.976 (4), -1.425 (4) and 0.632 (4) A. The crystal packing
      exhibits weak C-H?O inter-actions.

PMID- 22412586
TI  - 4,6-Dinitro-pyrogallol.
AB  - In the title mol-ecule, C(6)H(4)N(2)O(7), the two nitro groups are tilted with
      respect to the aromatic ring by 11.2 (1) and 10.9 (1) degrees . All three hy
      droxy groups are involved in the formation of bifurcated intra- and inter
      molecular O-H?O hydrogen bonds. The crystal packing exhibits short O?O distances
      of 2.823 (2) A between two O atoms of the nitro groups.

PMID- 22412587
TI  - (E)-3-Nitro-N'-(3-nitro-benzyl-idene)-benzohydrazide.
AB  - In the title compound, C(14)H(10)N(4)O(5), the mol-ecule exists in a trans
      conformation with respect to the methyl-idene unit. The dihedral angle between
      the benzene rings is 9.8 (2) degrees . In the crystal, mol-ecules are linked
      through N-H?O hydrogen bonds to form chains along the c axis.

PMID- 22412588
TI  - (E)-N'-(3-Fluoro-benzyl-idene)-3-nitro-benzohydrazide.
AB  - In the title compound, C(14)H(10)FN(3)O(3), the mol-ecule exists in a trans
      conformation with respect to the methyl-idene unit. The dihedral angle between
      the benzene rings is 5.1 (2) degrees . In the crystal, mol-ecules are linked
      through N-H?O hydrogen bonds, forming chains along the c axis.

PMID- 22412589
TI  - 6,6'-Dimethyl-2,2'-[1,3-diazinane-1,3-diyl-bis(methyl-ene)]diphenol.
AB  - In the mol-ecule of the title compound, C(20)H(26)N(2)O(2), the 1,3-diazinane
      ring adopts a slightly distorted chair conformation and the hy-droxy-benzyl
      substituents occupy equatorial positions on the N atoms of the heterocyclic ring.
      There are two intra-molecular O-H?N hydrogen bonds between the N atoms of the 1,3
      diazinane ring and the hy-droxy groups of the aromatic rings, with an S(6) set
      graph motif. However, the two observed intra-molecular hydrogen-bond distances
      were different. Considering that both N atoms experience the same chemical
      environment, it is surprising to see the difference in O?N distances [2.6771 (14)
      and 2.8123 (12) A]. The crystal structure is further stabilized by a C-H?pi
      interaction.

PMID- 22412590
TI  - Erythromycin A dimethyl sulfoxide disolvate 1.43-hydrate.
AB  - The title compound, C(37)H(67)NO(13).2C(2)H(6)OS.1.43H(2)O, is a macrolide anti
      biotic with better solubility and better dermal penetration abilities than
      erythromycin A itself. The asymmetric unit of this form contains one erythromycin
      A mol-ecule, two dimethyl sulfoxide (DMSO) solvent mol-ecules, a fully occupied
      water mol-ecule and a partially occupied water mol-ecule with an occupancy factor
      of 0.432 (11). The 14-membered ring of the erythronolide fragment has a
      conformation which differs considerably from that in erythromycin A dihydrate
      [Stephenson, Stowell, Toma, Pfeiffer & Byrn (1997 ?). J. Pharm. Sci.86, 1239
      1244]. One of the two DMSO mol-ecules is disordered over two orientations; the
      orientation depends on the presence or absence of the second, partially occupied,
      water mol-ecule. In the crystal, erythromycin mol-ecules are connected by O-H?O
      hydrogen bonds involving the hy-droxy groups and the fully occupied water mol
      ecule to form layers parallel to (010). These layers are connected along the b
      axis direction only by a possible hydrogen-bonding contact involving the
      partially occupied water mol-ecule.

PMID- 22412591
TI  - 3,6-Dimethyl-N,N-bis-(pyridin-2-yl)-1,2,4,5-tetra-zine-1,4-dicarboxamide.
AB  - In the title mol-ecule, C(16)H(16)N(8)O(2), four atoms of the tetra-zine ring are
      coplanar, with the largest deviation from the plane being 0.0236 (12) A; the
      other two atoms of the tetra-zine ring deviate on the same side from this plane
      by 0.320 (4) and 0.335 (4) A. Therefore, the central tetra-zine ring exhibits a
      boat conformation. The dihedral angles between the mean plane of the four
      coplanar atoms of the tetrazine ring and the two pyridine rings are 26.22 (10)
      and 6.97 (5) degrees . The two pyridine rings form a dihedral angle of 31.27 (8)
      degrees . In the molecule, there are a number of short C-H?O interactions. In the
      crystal, molecules are linked via a C-H?O interaction to form zigzag chains
      propagating along the [010] direction.

PMID- 22412592
TI  - (E)-1-[1-(3-Chloro-phen-yl)ethyl-idene]-2-(2,4-dinitro-phen-yl)hydrazine.
AB  - There are two crystallographically independent mol-ecules in the asymmetric unit
      of the title compound, C(14)H(11)ClN(4)O(4), with the same E conformation about
      the C=N double bond. The mol-ecules are approximately planar, with a dihedral
      angle between the benzene rings of 10.24 (12) degrees  in one mol-ecule and 4.73
      (12) degrees  in the other. In both mol-ecules, the ortho-nitro groups of the 2,4
      dinitro-phenyl units are coplanar to their bound benzene rings, whereas the para
      nitro groups are slightly twisted. In each mol-ecule, intra-molecular N-H?O
      hydrogen bonds generate S(6) ring motifs. In the crystal, mol-ecules are linked
      by weak C-H?O inter-actions into sheets parallel to the (-102) plane. These
      sheets are stacked by pi-pi inter-actions, with centroid-centroid distances of
      3.7008 (14) and 3.7459 (14) A. A Cl?O short contact [3.111 (2) A] is observed.

PMID- 22412593
TI  - 8,10-Diiodo-2,6-dioxo-4lambda-ioda-3,5-dioxatricyclo-[5.3.1.0]undeca-1(11),7,9
      triene-9-carb-oxy-lic acid.
AB  - In the title compound, C(9)HI(3)O(6).2H(2)O, the mol-ecule is located on a
      twofold axis that gives rise to disorder of the carboxyl group. This disorder is
      correlated with the disorder of one of the H atoms of the water mol-ecule. The
      carboxyl group is twisted relative to the attached benzene ring by 75.1 (4)
      degrees . The intra-molecular I?O distance is 2.112 (6) A. Mol-ecules are linked
      via O-H?O hydrogen bonding, C-I?O halogen bonding, with I?O distances in the
      range 3.156 (5)-3.274 (6) A, and dipolar C=O?C=O inter-actions between the
      carboxyl and carboxyl-ate groups, with an O?C distance of 2.944 (10) A.

PMID- 22412594
TI  - 2-Amino-3-(hy-droxy-meth-yl)pyridinium 2-benzoyl-benzoate monohydrate.
AB  - In the title hydrated salt, C(6)H(9)N(2)O(+).C(14)H(9)O(3) (-).H(2)O, the
      dihedral angle between the benzene rings of the 2-benzoyl-benzoate anion is 82.04
      (14) degrees , while the angles between the aromatic ring of the pyridinium
      cation and each of the benzene rings of the anion are 4.42 (14) and 82.04 (14)
      degrees . In the crystal, mol-ecules are linked by N-H?O and O-H?O hydrogen
      bonds, generating a three-dimensional network with R(2) (2)(8), R(6) (6)(16) and
      R(4) (4)(6) motifs. The crystal packing is further stabilized by two pi-pi inter
      actions, one between pyridinium rings, and another between the benzene benzoate
      and pyridinium rings of neighbouring mol-ecules, with centroid-to-centroid
      distances of 3.559 (2) and 3.606 (2) A, respectively.

PMID- 22412595
TI  - (E)-2-Chloro-N'-(4-hy-droxy-benzyl-idene)-benzohydrazide.
AB  - The title hydrazone mol-ecule, C(14)H(11)ClN(2)O(2), has a trans conformation
      with respect to the methyl-idene unit. The dihedral angle between the two benzene
      rings is 37.6 (3) degrees . In the crystal, the presence of O-H?O, O-H?N and N
      H?O hydrogen bonds leads to the formation of a three-dimensional network. The
      title compound crystallized in the chiral ortho-rhom-bic space group
      P2(1)2(1)2(1) and was refined as an inversion twin [Flack parameter = -0.20
      (18)].

PMID- 22412596
TI  - Dimethyl 6-bromo-2-methyl-1,2-di-hydro-quinoline-2,4-dicarboxyl-ate.
AB  - In the title compound, C(14)H(14)BrNO(4), the dihydro-pyridine ring adopts a
      screw-boat conformation. In the crystal, pairs of N-H?O hydrogen bonds link the
      mol-ecules into inversion R(2) (2)(10) dimers.

PMID- 22412597
TI  - 4-Benzyl-N-methyl-piperazine-1-carbothio-amide.
AB  - The asymmetric unit in the title thio-urea derivative, C(13)H(19)N(3)S, comprises
      three independent mol-ecules (A, B and C). The thio-urea groups are
      superimposable for the three mol-ecules, but there are significant conformational
      differences. Mol-ecules A and B are approximate mirror images of each other, and
      mol-ecule C has an inter-mediate conformation. The dihedral angles between the
      thio-urea groups and the phenyl rings are 52.10 (5), 63.29 (5) and 66.46 (6)
      degrees  in mol-ecules A, B and C, respectively. Each independent mol-ecule self
      associates into a supra-molecular chain along [100] via N-H?S hydrogen bonds. Mol
      ecules of A and B assemble into layers four mol-ecules thick in the ac plane via
      C-H?S and C-H?pi inter-actions. Mol-ecules of C self-assemble into layers in the
      ac plane via C-H?S inter-actions. The layers stack along the b axis with no
      specific inter-actions between them.

PMID- 22412598
TI  - Diethyl 4,4'-(3,6-dioxaoctane-1,8-diyl-dioxy)dibenzoate.
AB  - The title compound, C(24)H(30)O(8), was obtained by reaction of ethyl 4-hy-droxy
      benzoate with 1,2-dichloro-ethane. The mol-ecule occupies a crystallographic
      inversion center, with its central ethyl-ene bridge in an anti conformation. The
      other ethyl-ene bridge has a gauche conformation, with the corresponding O-C-C-O
      torsion angle being 74.2 (1) degrees . The benzene rings are almost coplanar with
      the adjacent eth-oxy-carbonyl groups, with an r.m.s. deviation of 0.078 A.

PMID- 22412599
TI  - 10alpha-Hy-droxy-13-{[4-(4-meth-oxy-phen-yl)piperazin-1-yl]meth-yl}-4,9-dimethyl
      3,8,15-trioxatetra-cyclo-[10.3.0.0.0]penta-decan-14-one.
AB  - The title compound, C(26)H(36)N(2)O(6), was synthesized from 9alpha-hy-droxy
      parthenolide (9alpha-hy-droxy-4,8-dimethyl-12-methylen-3,14-dioxa-tricyclo
      [9.3.0.0(2,4)]tetra-dec-7-en-13-one), which was isolated from the chloro-form
      extract of the aerial parts of Anvillea radiata. The mol-ecule is built up from
      fused five- and ten-membered rings with two additional ep-oxy ring systems and a
      meth-oxy-phenyl-piperazine group as a substituent. The ten-membered ring adopts
      an approximate chair-chair conformation, while the piperazine ring displays a
      chair conformation and the five-membered ring shows an envelope conformation with
      the C atom closest to the hy-droxy group forming the flap. The mol-ecular
      conformation is determined by an O-H?N hydrogen bond between the hy-droxy group
      and a piperazine N atom. The crystal structure is built up by weak C-H?O inter
      actions.

PMID- 22412600
TI  - 3-Benzyl-6-methyl-2-sulfanylidene-2,3-di-hydroquinazolin-4(1H)-one.
AB  - In the title compound, C(16)H(14)N(2)OS, the quinazoline ring system is
      essentially planar, with a maximum deviation of 0.029 (3) A. The dihedral angle
      between the quinazoline and benzene rings is 88.4 (2) degrees . In the crystal,
      adjacent mol-ecules are connected via pairs of N-H?S and C-H?O hydrogen bonds,
      which generate R(2) (2)(8) and R(2) (2)(10) graph-set motifs, respectively,
      resulting in a supra-molecular chain along the a axis.

PMID- 22412601
TI  - 2-(4-{4-[4-(Oxiran-2-ylmeth-oxy)phen-oxy]phen-yl}phen-oxy-meth-yl)oxirane.
AB  - In the title ep-oxy monomer, C(24)H(22)O(5), the dihedral angle in the biphenyl
      residue is 3.34 (19) degrees , indicating a nearly coplanar conformation; this
      residue is not planar with the adjacent benzene ring [dihedral angle = 58.93 (14)
      degrees ]. Each of the epoxide rings is disordered. Each epoxide ring was
      resolved over two alternative positions with site-occupancy ratios of 0.638
      (10):0.362 (10) and 0.797 (9):0.203 (9).

PMID- 22412602
TI  - 6,7-Bis(bromo-meth-yl)-2,11,18,21,24,27-hexa-oxatetra-cyclo
      [26.4.0.0.0]dotriaconta-1(28),4,6,8,12(17),13,15,29,31-nona-ene dichloro-methane
      monosolvate.
AB  - The title 20-crown-6 unit, C(28)H(30)Br(2)O(6).CH(2)Cl(2), consisting of three
      benzo groups and triethyl-ene glycol was prepared from the reaction of 1,2,4,5
      tetra-kis-(bromo-meth-yl)benzene and bis-phenol in the presence of sodium
      hydride. In the crystal, one O atom of the central ethyl-ene glycol in the
      triethyl-ene glycol unit exhibits an exo conformation as a result of intra
      molecular C-H?O hydrogen bonds. The crown unit and the solvent mol-ecule are
      linked by weak C-H?O hydrogen bonds.

PMID- 22412603
TI  - 5-Sulfanyl-idene-2H,5H-1,3-dithiolo[4,5-d][1,3]dithiol-2-one.
AB  - The title mol-ecule, C(4)OS(5), is essentially planar, with an r.m.s. deviation
      of 0.032 (3) A. All the C-S single bonds are shorter than the standard Csp(3)-S
      single-bond length, showing the pi-conjugated nature of the molecule. In the
      crystal, molecules lie parallel to one another and pack in columns along the a
      axis. Short inter-molecular S?S contacts [3.314 (3), 3.482 (2) and 3.501 (2) A]
      are observed between the columns. The angle between the two mol-ecular dipole
      moments in the unit cell is 39.3 (1) degrees  and the macro-polarization vector
      is along the [1 0 - 1.41] direction. As a result of the high polarization and pi
      conjugation of the structure, the crystalline powder exhibits a second harmonic
      generating intensity, which is as strong as that of the urea standard powder
      crystals, when irradiated by a 1053 nm laser beam. The diffraction space of the
      crystal showed a nonmerohedral twinning.

PMID- 22412604
TI  - 2-(Hy-droxy-meth-yl)pyridin-3-ol.
AB  - In the crystal structure of the title compound, C(6)H(7)NO(2), the mol-ecules are
      are linked by inter-molecular O-H?N and O-H?O hydrogen bonds; pi-pi stacking is
      observed between parallel pyridine rings of adjacent mol-ecules [centroid-to
      centroid distance = 3.7649 (12) A].

PMID- 22412605
TI  - 2-Chloro-N-(3-methyl-phen-yl)benzamide.
AB  - In the structure of the title compound, C(14)H(12)ClNO, the ortho-Cl atom in the
      benzoyl ring is positioned syn to the C=O bond, while the meta-methyl group in
      the aniline ring is positioned anti to the N-H bond. The amide group forms
      dihedral angles of 60.1 (1) and 22.0 (1) degrees , respectively, with the benzoyl
      and aniline rings, while the angle between these rings is 38.7 (1) degrees . The
      crystal structure is stabilized by N-H?O hydrogen bonds, which give rise to
      infinite chains running along the c axis.

PMID- 22412606
TI  - 1-(3,5-Dichloro-phen-yl)-3-(2-meth-oxy-phen-yl)triaz-1-ene.
AB  - The title mol-ecule, C(13)H(11)Cl(2)N(3)O, is almost planar and adopts a trans
      conformation with respect to the -N=N- bond; the dihedral angle between the rings
      is 3.47 (2) degrees . The N-N bond lengths indicate the presence of single- and
      double-bond characters and hence the -N=N-NH- moiety. In the crystal, inversion
      dimers linked by pairs of N-H?Cl hydrogen bonds occur, and C-H?pi and pi-pi
      stacking interactions are also observed.

PMID- 22412607
TI  - 3-Carbamoyl-2,2-dimethyl-cyclo-pentane-1,1-dicarb-oxy-lic acid.
AB  - In the title compound, C(10)H(15)NO(5), the five-membered cyclo-pentane ring has
      an envelope conformation, with four atoms lying in a plane (mean deviation =
      0.0213 A), while the fifth atom deviates from this plane by 0.626 (2) A. A three
      dimensional structure is formed through N-H?O and O-H?O hydrogen bonds between
      the amide and carb-oxy-lic acid groups and both carb-oxy-lic acid and amide O
      atom acceptors.

PMID- 22412608
TI  - N-(2-Iodo-phen-yl)benzene-carbox-imid-amide.
AB  - The title compound, C(13)H(11)IN(2), crystallizes with two independent molecules
      (A and B) in the asymmetric unit. The two aromatic rings are inclined to one
      another by 73.3 (2) degrees  in molecule A, and by 74.4 (1) degrees  in molecule
      B. In molecule A, the iodophenyl and the phenyl rings are inlclined to the N=C-N
      plane by 88.0 (4) and 19.0 (4) degrees , respectively. In molecule B the
      corresponding angles are 85.0 (4) and 20.7 (4) degrees , respectively. In the
      crystal, the two molecules are not parallel but have a dihedral angle between the
      iodophenyl rings of 8.6 (1) degrees , and 44.5 (2) degrees  between the phenyl
      rings. The A and B molecules are linked vvia N-H?N hydrogen bonds to form -A-B-A
      B- chains propagating along direction [100].

PMID- 22412609
TI  - (E)-N-Butyl-3-(3,4-dihy-droxy-phen-yl)acryl-amide hemihydrate.
AB  - In the title compound, C(13)H(17)NO(3).0.5H(2)O, a new caffeic acid amide
      derivative, the solvent water mol-ecule lies on a twofold axis and the terminal
      ethyl group appears disordered with occupancy factors of 0.525 (6) and 0.475 (6).
      The benzene ring makes an angle of 17.3 (2) degrees  with the C=C-C-O linker. The
      presence of an ethyl-enic spacer in the caffeic acid amide mol-ecule allows the
      formation of a conjugated system, strongly stabilized through pi-electron
      delocalization. The C=C double bond in the linker is trans, similar to those
      previously reported in caffeic esters. The crystal is stabilized by O-H?O, N-H?O
      and C-H?O hydrogen bonds. The mol-ecules of the caffeic acid amide form a
      supermolecular planar structure through O-H?O hydrogen bonds between a hy-droxy
      group of one caffeic acid mol-ecule and a carbonyl O atom of another. These
      planes inter-act via C-H?O, O-H?O and N-H?O hydrogen bonds to form a three
      dimensional network.

PMID- 22412610
TI  - Methyl 2-[(2-methyl-phen-oxy)meth-yl]benzoate.
AB  - In the title methyl-benzoate compound, C(16)H(16)O(3), the mol-ecule is
      essentially planar (r.m.s. of all fitted non-H atoms = 0.0370 A); the dihedral
      angle between the phenyl rings is 2.30 (7) degrees . Apart from a C-H?pi inter
      action, no marked inter-molecular contacts are obvious.

PMID- 22412611
TI  - (Z)-3-(1H-Indol-3-yl)-2-(3,4,5-tri-methoxy-phen-yl)acrylonitrile.
AB  - In the title compound, C(20)H(18)N(2)O(3), the C=C bond of the acrylonitrile
      group that links the indole and the 3,4,5-trimeth-oxy-phenyl rings has Z
      geometry, with dihedral angles between the plane of the acrylonitrile unit and
      the planes of the benzene and indole ring systems of 21.96 (5) and 38.94 (7)
      degrees , respectively. The acrylonitrile group is planar (r.m.s. deviation from
      planarity = 0.037 A). Mol-ecules are linked into head-to-tail chains that
      propagate along the b-axis direction by bifurcated N-H?O inter-molecular hydrogen
      bonds, which form an R(1) (2)(5) motif between the indole NH group and the two
      meth-oxy O atoms furthest from the nitrile group.

PMID- 22412612
TI  - (Z)-2-{2,4-Dimeth-oxy-6-[(E)-4-meth-oxy-styr-yl]benzyl-idene}quinuclidin-3-one.
AB  - The crystal structure of the title compound, C(25)H(27)NO(4), shows the presence
      of a double bond with Z geometry which connects the quinuclidin-3-one ring and
      the trimeth-oxy-resveratrol moiety. The dihedral angle between the two benzene
      rings in the stilbene skeleton is 32.80 (8) degrees .

PMID- 22412613
TI  - (Z)-3-(1-Benzofuran-2-yl)-2-(3,4,5-tri-meth-oxy-phen-yl)acrylonitrile.
AB  - In the title compound, C(20)H(17)NO(4), the double bond of the acrylonitrile
      group separating the 1-benzofuran moiety from the 3,4,5-trimeth-oxy-phenyl ring
      has Z geometry. The 1-benzofuran groups are pi-pi stacked with inversion-related
      counterparts such that the furan ring centroid-centroid distance is 3.804 (5) A.
      The dihedral angle between the planes of the trimeth-oxy-phenyl ring and the
      acrylonitrile group is 24.2 (2) degrees .

PMID- 22412614
TI  - 2-Methyl-3-(2-methyl-phen-yl)-4-oxo-3,4-dihydro-quinazolin-8-yl benzoate.
AB  - In the title quinazolin-4-one derivative, C(23)H(18)N(2)O(3), both the benzoate
      [dihedral angle = 79.99 (6) degrees ] and the 2-tolyl [89.02 (7) degrees ] groups
      are close to orthogonal to the central fused ring system. Both aryl groups are
      orientated towards the quinazolin-4-one-bound methyl group. In the crystal, mol
      ecules are connected into a three-dimensional architecture by C-H?O, C-H?N and C
      H?pi inter-actions.

PMID- 22412615
TI  - 2-Methyl-3-(2-methyl-phen-yl)-4-oxo-3,4-dihydro-quinazolin-8-yl 4-methyl
      benzoate.
AB  - In the title quinazolin-4-one derivative, C(24)H(20)N(2)O(3), both the 4-methyl
      benzoate [dihedral angle = 83.90 (9) degrees ] and 2-tolyl [87.88 (9) degrees ]
      groups are almost orthogonal to the central fused ring system. These aryl groups
      are oriented towards the quinazolin-4-one-bound methyl group. In the crystal, mol
      ecules are connected into a three-dimensional architecture by C-H?O, C-H?pi and
      pi-pi [ring centroid-to-centroid separation = 3.6458 (13) A] inter-actions.

PMID- 22412616
TI  - 4-Oxo-2,4-diphenyl-butane-nitrile.
AB  - The title mol-ecule, C(16)H(13)NO, is twisted, the dihedral angle between the
      terminal phenyl rings being 68.40 (6) degrees . In the crystal, C-H?O and C-H?N
      inter-actions lead to supra-molecular layers in the bc plane.

PMID- 22412618
TI  - 4-Chloro-anilinium tetra-fluoro-borate 18-crown-6 clathrate.
AB  - In the title compound, C(6)H(7)ClN(+).BF(4) (-).C(12)H(24)O(6), the complete
      cation is generated by crystallographic mirror symmetry, with two C atoms and the
      N and Cl atoms lying on the mirror plane. The complete crown ether is also
      generated by mirror symmetry, as is the anion (in which the B and two F atoms lie
      on the mirror plane). The -NH(3) (+) group of the cation inserts into the crown
      ether ring and forms bifurcated N-H?(O,O) hydrogen bonds. The H atoms of the 
      NH(3) (+) group were modelled as disordered across the mirror plane.

PMID- 22412617
TI  - 2-(4-Meth-oxy-phen-yl)-4-oxo-4-phenyl-butane-nitrile.
AB  - The title mol-ecule, C(17)H(15)NO(2), is twisted, the dihedral angle between the
      terminal benzene rings being 63.30 (6) degrees . In the crystal, C-H?O and C-H?N
      inter-actions lead to supra-molecular layers in the ab plane. These are connected
      along the c axis via C-H?pi inter-actions.

PMID- 22412619
TI  - 2,4,5-Trichloro-anilinium perchlorate 18-crown-6 clathrate.
AB  - In the title compound, C(6)H(5)Cl(3)N(+).ClO(4) (-).C(12)H(24)O(6), the
      perchlorate anion is disordered over two orientations in a 0.666 (17):0.334 (17)
      ratio. The ammonium group of the organic cation inserts into the crown ether ring
      and forms three bifurcated N-H?(O,O) hydrogen bonds to generate a supra-molecular
      complex. The macrocycle has approximate D(3d) local symmetry.

PMID- 22412620
TI  - 2,4-Dichloro-7-fluoro-quinazoline.
AB  - The mol-ecule of the title compound, C(8)H(3)Cl(2)FN(2), is essentially planar,
      with a maximum deviation of 0.018 (2) A. In the crystal, pi-pi stacking is
      observed between parallel quinazoline moieties of adjacent mol-ecules, the
      centroid-centroid distance being 3.8476 (14) A.

PMID- 22412621
TI  - 12-{[4-(2-Fluoro-phen-yl)piperazin-1-yl]-meth-yl}-9alpha-hy-droxy-4,8-dimethyl
      3,14-dioxatricyclo-[9.3.0.0]tetra-dec-7-en-13-one.
AB  - The title compound, C(25)H(33)FN(2)O(4), was synthesized from 9alpha-hy-droxy
      parthenolide (9alpha-hy-droxy-4,8-dimethyl-12-methyl-ene-3,14-dioxatricyclo
      [9.3.0.0(2,4)]tetra-dec-7-en-13-one), which was isolated from the chloro-form
      extract of the aerial parts of Anvillea radiata. The asymmetric unit contains two
      independent mol-ecules. In each mol-ecule, the ten-membered ring displays an
      approximative chair-chair conformation. Each of the piperazine rings adopts a
      perfect chair conformation, while both lactone rings show an envelope
      conformation, one with the C atom bearing the piperazin-1-ylmethyl group as the
      flap, the other with the junction C atom not attached to the ring O atom as the
      flap. The dihedral angles between the least-squares planes through the ten- and
      five-membered rings in the two mol-ecules are similar [19.1 (3) and 16.2 (3)
      degrees ]. An intra-molecular O-H?N hydrogen bond stabilizes the mol-ecular
      conformation. The crystal packing is stabilized by C-H?O hydrogen bonds.

PMID- 22412622
TI  - 1,3-Bis(1-cyclo-hexyl-eth-yl)imidazolidine-2-thione.
AB  - The complete mol-ecule of the title compound, C(19)H(34)N(2)S, is generated by
      crystallographic twofold symmetry, with the C=S group lying on the rotation axis.
      A short C-H?S contact occurs in the mol-ecule. The five-membered ring is twisted
      and the cyclo-hexyl ring adopts a chair conformation. The dihedral angle between
      the mean plane of the five-membered ring and the basal plane of the cyclo-hexyl
      ring is 75.32 (13) degrees .

PMID- 22412623
TI  - 5-Fluoro-6'H,7'H,8'H-spiro-[indoline-3,7'-pyrano[3,2-c:5,6-c']di-1-benzopyran]
      2,6',8'-trione.
AB  - In the title compound, C(26)H(12)FNO(6), the central pyran ring and both
      benzopyran systems are nonplanar, having total puckering amplitudes of 0.139 (2),
      0.050 (1) and 0.112 (2) A, respectively. The central pyran ring adopts a boat
      conformation. The crystal structure is stabilized by C-H?O, N-H?O, N-H?F and C
      H?pi inter-actions.

PMID- 22412624
TI  - dl-Methyl 4-(4-meth-oxy-phen-yl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro
      quinoline-3-carboxyl-ate.
AB  - In the title compound, C(21)H(25)NO(4), the dihydropyridine ring adopts a
      flattened boat conformation. The N atom and the sp(3) C atom deviate in the same
      direction from the mean plane of the other four C atoms, by 0.269 (6) and 0.111
      (6) A, respectively. This mean plane is inclined to the 4-methoxy-phenyl ring by
      87.3 (5) degrees . The cyclohexenone ring has a sofa conformation with the C atom
      bearing the methyl groups deviating from the mean plane through the other five C
      atoms by 0.628 (6) A. There is a short C-H?O hydrogen bond in the molecule. In
      the crystal, molecules are linked by an N-H?O hydrogen bond to form chains
      propagating along the c-axis direction.

PMID- 22412625
TI  - 1,3,5-Tris(pyridin-3-yl)-2,4-diaza-penta-1,4-diene.
AB  - In the solid state, the structure of the title compound, C(18)H(15)N(5), is
      stabilized by weak C-H?N interactions. Mol-ecules are arranged in layers parallel
      to the bc plane forming an inter-esting supra-molecular structure.

PMID- 22412626
TI  - Ethyl 2-[(tert-but-oxy-carbon-yl)amino]-thia-zole-5-carboxyl-ate.
AB  - In the crystal of the title compound, C(11)H(16)N(2)O(4)S, molecules are linked
      via pairs of N-H?N hydrogen bonds to form inversion dimers. The dimers are linked
      by a weak C-H?O interaction to form chains propagating along direction [100].

PMID- 22412627
TI  - rac-7-[(2E)-But-2-eno-yl]-13-chloro-N-cyclo-hexyl-7,8-dihydro-5H-isochromeno[4,3
      c]phenanthridine-8-carboxamide.
AB  - In the title compound, C(31)H(29)ClN(2)O(3), the two heterocyclic rings,
      belonging to a system of five condensed rings, adopt conformations intermediate
      between twist-boat and sofa. The secondary amide group is involved in a weak
      intramolecular N-H?N hydrogen bond. In the crystal, molecules are linked by pairs
      of C-H?Cl hydrogen bonds to form inversion dimers. These dimers are linked via a
      C-H?O interaction to form chains propagating along the b-axis direction.

PMID- 22412628
TI  - rac-3-[(Anilino)(naphthalen-2-yl)-methyl]thian-4-one.
AB  - In the title compound, C(22)H(21)NOS, the thio-pyran-one ring adopts a chair-like
      conformation with the substituent in the axial position. The relative
      configuration of the racemic compound is 3R,7S according to the numbering scheme
      used in this publication. In the crystal packing, centrosymmetric dimers are
      built up via N-H?O hydrogen bonds, with graph set R(2) (2)(8).

PMID- 22412629
TI  - 3-(4-Bromo-phenyl-sulfin-yl)-5-fluoro-2-methyl-1-benzofuran.
AB  - There are two symmetry-independent mol-ecules, A and B, in the asymmetric unit of
      the title compound, C(15)H(10)BrFO(2)S. The dihedral angle formed by the 4-bromo
      phenyl ring and the mean plane of the benzofuran fragment is 88.26 (6) degrees 
      in mol-ecule A and 88.25 (6) degrees  in mol-ecule B. In the crystal, mol-ecules
      are linked by weak inter-molecular C-H?F, C-H?O and C-H?pi inter-actions. The
      crystal structure also exhibits inter-molecular C-Br?pi [3.737 (3) A] inter
      actions, and weak pi-pi inter-actions between the benzene and furan rings of
      neighbouring mol-ecules [centroid-centroid distance = 3.557 (3) A, inter-planar
      distance = 3.421 (3) A and slippage = 0.974 (3) A].

PMID- 22412630
TI  - (7aS)-(-)-Dimeth-yl(1-oxido-3-oxo-5,6,7,7a-tetra-hydro-3H-pyrrolizin-2
      yl)sulfonium.
AB  - In the zwitterionic title compound, C(9)H(13)NO(2)S, the pyrrolidine heterocycle
      adopts an envelope conformation (with the C atom in the 7-position as the flap).
      The negative charge is delocalized over the two carbonyl groups and the C atom
      connecting them. The positive charge is located on the S atom. Two inter
      molecular C-H?O inter-actions are observed. The molecular geometry at the S atom
      is trigonal pyramidal.

PMID- 22412631
TI  - 6-[(2-Chloro-pyridin-5-ylmeth-yl)(eth-yl)-azan-yl]-4-(2-fluoro-phen-yl)-1-methyl
      5-nitro-1,2,3,4-tetra-hydro-pyridin-2-one.
AB  - In the title compound, C(20)H(20)ClFN(4)O(3), the tetra-hydro-pyridone ring
      adopts a skew boat conformation. The dihedral angle between the mean planes of
      the benzene and pyridine rings is 80.7 (3) degrees . In the crystal, weak C-H?O
      inter-actions are observed.

PMID- 22412632
TI  - 2,2'-(4-Methyl-4H-1,2,4-triazole-3,5-di-yl)dibenzene-sulfonamide.
AB  - In the title compound, C(15)H(15)N(5)O(4)S(2), the dihedral angles between the
      central 1,2,4-triazole ring and the pendant benzene rings are 55.61 (10) and
      68.59 (10) degrees ; the dihedral angle between the benzene rings is 63.66 (9)
      degrees . Intra-molecular N-H?N and N-H?O hydrogen bonds generate S(7) and S(12)
      rings, respectively. In the crystal, sheets extending in the (101) plane arise,
      with the mol-ecules linked by C-H?O, N-H?N and N-H?O inter-actions. A C-H?pi
      inter-action further consolidates the structure.

PMID- 22412633
TI  - (2E)-2-(4-Bromo-benzyl-idene)-2,3-di-hydro-1H-inden-1-one.
AB  - The title indan-1-one derivative, C(16)H(11)BrO, is planar, the r.m.s. deviation
      for all 18 non-H atoms being 0.071 A. The configuration about the C=C bond [1.337
      (5) A] is E. In the crystal, supra-molecular layers in the ab plane are formed by
      C-H?O inter-actions, involving the bifurcated carbonyl O atom, as well as C-H?pi
      inter-actions. The studied crystal was an inversion twin.

PMID- 22412634
TI  - 2-Methyl-3-(2-methyl-phen-yl)-4-oxo-3,4-dihydro-quinazolin-8-yl thio-phene-2
      carboxyl-ate.
AB  - In the title compound, C(21)H(16)N(2)O(3)S, the central quinazolin-4-one ring is
      planar (r.m.s. deviation = 0.037 A). The N-bound benzene and thio-phenyl rings
      are almost perpendicular to the central plane [dihedral angles = 82.22 (5) and
      77.05 (13) degrees , respectively]. Mol-ecules are connected into a three
      dimensional array by C-H?O inter-actions involving both carbonyl O atoms. The
      thio-phene ring is disordered over two positions, which are approximately
      parallel and oppositely orientated. The major component refined to a site
      occupancy factor of 0.6555 (17).

PMID- 22412635
TI  - 6-Meth-oxy-2-phenyl-4,4a,6,7,8,8a-hexa-hydro-2H-pyrano[3,2-d][1,3]dioxine-7,8
      diyl bis-(4-methyl-benzene-1-sulfonate).
AB  - In the title alpha-D-glucopyran-oside derivative, C(28)H(30)O(10)S(2), each
      heterocyclic ring adopts a chair conformation. In the tri-substituted ring, the
      meth-oxy and one sulfonate group occupy axial positions, whereas the second
      sulfonate group occupies an axial position. The phenyl group on the other ring is
      in an equatorial position. In the crystal, supra-molecular chains propagating
      along [100] are formed through C-H?O and C-H?pi inter-actions.

PMID- 22412636
TI  - 2-Methyl-3-(2-methyl-phen-yl)-4-oxo-3,4-dihydro-quinazolin-8-yl 4-bromo-benzene-1
      sulfonate.
AB  - The title mol-ecule, C(22)H(17)BrN(2)O(4)S, has a twisted U shape, the dihedral
      angle between the quinazolin-4-one and bromo-benzene ring systems being 46.25 (8)
      degrees . In order to avoid steric clashes with adjacent substituents on the
      quinazolin-4-one ring, the N-bound tolyl group occupies an orthogonal position
      [dihedral angle = 89.59 (8) degrees ]. In the crystal, mol-ecules are connected
      into a three-dimensional architecture by C-H?O inter-actions, with the ketone O
      atom accepting two such bonds and a sulfonate O atom one.

PMID- 22412637
TI  - 1-Iodo-4-meth-oxy-2-nitro-benzene.
AB  - In the title compound, C(7)H(6)INO(3), the 12 non-H atoms are planar, with an
      r.m.s. deviation of 0.016 A. A close intra-molecular I?O inter-action [3.0295
      (13) A] is present. Inter-molecular I?O inter-actions [3.3448 (13) A] lead to the
      formation of zigzag chains along the b axis. These are assembled into layers by
      weak pi-pi inter-actions [centroid-centroid distance = 3.8416 (9) A], and the
      layers stack along the a axis, being connected by C-H?O contacts.

PMID- 22412638
TI  - 4-{(4Z)-4-[(2Z)-3-(4-Fluoro-anilino)-1-hy-droxy-but-2-en-1-yl-idene]-3-methyl-5
      oxo-4,5-dihydro-1H-pyrazol-1-yl}-benzene-sulfonamide.
AB  - In the title compound, C(20)H(19)FN(4)O(4)S, the pyrazole and benzene-sulfonamide
      rings are coplanar [dihedral angle = 5.02 (15) degrees ] but this planarity does
      not extend over the entire mol-ecule, the dihedral angle between the terminal six
      membered rings being 33.24 (14) degrees . Intra-molecular hy-droxy-hy-droxy O-H?O
      and amine-hy-droxy N-H?O hydrogen bonds, as a well as a tight C-H?O(carbon-yl)
      inter-action, lead to a sequence of three fused S(6) rings. Supra-molecular
      chains along the a axis feature in the crystal packing; these chains are
      stabilized by amine-sulfonamide N-H?O and amine-pyrazole N-H?N hydrogen bonds.

PMID- 22412639
TI  - (2Z)-3-(4-Fluoro-anilino)-1-(5-hy-droxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)but-2
      en-1-one.
AB  - The central carbonyl group in the title compound, C(20)H(18)FN(3)O(2), forms
      amine-hy-droxy N-H?O and hy-droxy-hy-droxy O-H?O hydrogen bonds, leading to two
      S(6) rings. The N-bound phenyl ring is coplanar with the five-membered ring to
      which it is attached [dihedral angle = 6.27 (10) degrees ], but an overall twist
      in the mol-ecule is evident, the dihedral angle between the terminal phenyl and
      benzene rings being 27.30 (10) degrees . Mol-ecules aggregate into a three
      dimensional architecture via C-H?F, C-H?O and C-H?pi inter-actions.

PMID- 22412640
TI  - 2-{(E)-1-[2-(2-Nitro-phen-yl)hydrazin-1-yl-idene]eth-yl}benzene-1,3-diol mono
      hydrate.
AB  - The hydrazone mol-ecule in title monohydrate, C(14)H(13)N(3)O(4).H(2)O, is almost
      coplanar, the dihedral angle between the terminal benzene rings being 3.22 (15)
      degrees ; the nitro group is coplanar with the benzene ring to which it is bonded
      [O-N-C-C = -2.8 (4) degrees ]. The hy-droxy group forms an intra-molecular
      hydrogen bond with the imine N atom, and the conformation about the imine bond
      [1.305 (3) A] is E. In the crystal, supra-molecular layers in the (203) plane are
      connected into a double layer via water-nitro O-H?O hydrogen bonds, along with pi
      pi inter-actions [ring centroid-centroid distance = 3.7859 (19) A].

PMID- 22412641
TI  - 1-{2-[(4-Chloro-benzyl-idene)amino]phen-yl}-3-phenyl-thio-urea.
AB  - The asymmetric unit of the title compound, C(20)H(16)ClN(3)S, contains two
      independent mol-ecules, A and B. In mol-ecule A, the dihedral angles between the
      central benzene ring and the pendant chloro-benzene and phenyl rings are 6.37
      (15) and 64.79 (15) degrees , respectively. The corresponding values in mol-ecule
      B are 28.21 (14) and 82.11 (16) degrees , respectively. Each mol-ecule features
      an intra-molecular N-H?N hydrogen bond, which generates an S(5) ring. In the
      crystal, mol-ecules A and B form dimers, being linked by two N-H?S hydrogen bonds
      with graph-set notation R(2) (2)(8).

PMID- 22412642
TI  - 1,1'-[(2-Bromo-phen-yl)-methyl-ene]-dipyrrolidin-2-one.
AB  - In the title compound, C(15)H(17)BrN(2)O(2), both pyrrolidinone rings adopt
      envelope conformations. The crystal packing is characterized by short C-Br?O=C
      inter-actions [Br?O = 3.1730 (13) A], leading to supra-molecular dimers. Inter
      molecular C-H?O and C-H?pi inter-actions are also observed.

PMID- 22412643
TI  - 5-({[(E)-Benzyl-idene-amino]-oxy}meth-yl)-1,3,4-thia-diazol-2-amine.
AB  - In the mol-ecule of the title compound, C(10)H(10)N(4)OS, the configuration about
      the C=N double bond is E. The dihedral angle between the thia-diazole and benzene
      rings is 81.1 (1) degrees . In the crystal, mol-ecules are linked by N-H?N and C
      H?O hydrogen bonds to form a two-dimensional network parallel with the bc plane.

PMID- 22412644
TI  - (E)-(2-Chloro-benzyl-idene)amino 2-amino-4-chloro-benzoate.
AB  - In the title compound, C(14)H(10)Cl(2)N(2)O(2), the configuration about the C=N
      double bond is E and the dihedral angle between the benzene rings is 1.75 (5)
      degrees . An intra-molecular N-H?O inter-action generates an S(6) ring. In the
      crystal, mol-ecules are linked by N-H?O hydrogen bonds, resulting in [101]
      chains.

PMID- 22412645
TI  - 4,4,5,5-Tetra-methyl-2-[1,3,6,8-tetra-bromo-7-(4,4,5,5-tetra-methyl-1,3,2
      dioxaborolan-2-yl)pyren-2-yl]-1,3,2-dioxaborolane.
AB  - The complete mol-ecule of the title compound, C(28)H(28)B(2)Br(4)O(4), is
      generated by the application of a centre of inversion. In the mol-ecule, the
      BO(2) plane is perpendicular to that through the pyrene ring [dihedral angle =
      86.27 (13) degrees ]. In the crystal, mol-ecules stack into columns along the b
      axis, the closest contact between these being of the type C-Br?pi.

PMID- 22412646
TI  - 4-Bromo-N-(4-hy-droxy-benzyl-idene)-aniline.
AB  - In the title compound, C(13)H(10)BrNO, the benzene ring planes are inclined at an
      angle of 48.85 (17) degrees , resulting in a nonplanar mol-ecule. A
      characteristic of aromatic Schiff bases with N-aryl substituents is that the
      terminal phenyl rings are twisted relative to the HC=N plane. In this case, the
      HC=N unit makes dihedral angles of 11.1 (4) and 38.5 (3) degrees  with the hy
      droxy-benzene and bromo-benzene rings, respectively. In the crystal, the
      molecules are linked by O-H?N hydrogen bonds to form infinite (C8) chains along
      the b axis.

PMID- 22412647
TI  - (R)-N-(3-Meth-oxy-phen-yl)-tert-butane-sulfinamide.
AB  - The title compound, C(11)H(17)NO(2)S, was obtained by the reaction of (R)-tert
      butane-sulfinamide with 3-meth-oxy-phenyl bromide in toluene. In the crystal, mol
      ecules inter-act head-to-tail through N-H?O and C-H?O hydrogen bonds, forming one
      dimensional chains parallel to the a axis.

PMID- 22412648
TI  - (E)-2-{4-[(Pyridin-2-yl)methyl-idene-amino]-phen-yl}acetic acid.
AB  - The title mol-ecule, C(14)H(12)N(2)O(2), forms a dimeric unit linked by a pair of
      symmetry-equivalent O-H?N hydrogen bonds. The aromatic rings are significantly
      twisted from each other with a dihedral angle of 44.04 (4) degrees .

PMID- 22412649
TI  - Methyl (Z)-2-[(4-bromo-2-formyl-phen-oxy)meth-yl]-3-(4-methyl-phen-yl)acrylate.
AB  - In the title compound, C(19)H(17)BrO(4), the dihedral angle between the two
      benzene rings is 82.9 (2) degrees . The mol-ecular structure is stabilized by an
      intra-molecular C-H?O hydrogen bond, which generates an S(7) ring motif. The
      crystal packing is stabilized by C-H?O hydrogen bonds, which generate two
      centrosymmetic ring systems with R(2) (2)(18) and R(2) (2)(14) graph-set motifs.
      The crystal packing is further stabilized by inter-molecular pi-pi inter-actions
      [centroid-centroid distance = 3.984 (2) A].

PMID- 22412650
TI  - (E)-3-(2-Bromo-phen-yl)-1-(3,4-dimeth-oxy-phen-yl)prop-2-en-1-one.
AB  - The crystal structure of the title compound, C(17)H(15)BrO(3), a chalcone
      derivative, exhibits two crystallographically independent mol-ecules per
      asymmetric unit showing an E conformation about the ethyl-ene double bond. In
      each mol-ecule, the two phenyl rings are almost coplanar: the mean planes make
      dihedral angles of 9.3 (2) and 19.4 (2) degrees . In the crystal, mol-ecules are
      linked through weak inter-molecular C-H?O hydrogen bonds.

PMID- 22412651
TI  - N-Benzyl-isatin.
AB  - In the title compound, C(15)H(11)NO(2), two C-H?O hydrogen bonds are observed in
      the crystal structure, as well as pi-pi stacking with a centroid-centroid
      distance of 3.623 (2) A. The planarity of the two ring systems is illustrated by
      very small deviations of all the atoms from these planes [largest deviations =
      0.003 (3) and 0.010 (3) A for the phenyl and fused-benzene rings, respectively].
      The dihedral angle between these two planes is 77.65 (9) degrees .

PMID- 22412652
TI  - (2E,6E)-2,6-Bis(2,6-dichloro-benzyl-idene)-cyclo-hexa-none.
AB  - The title compound, C(20)H(14)Cl(4)O, was prepared by the reaction of 2,6
      dichloro-benzaldehyde and cyclo-hexa-none. In the mol-ecule, the central cyclo
      hexa-none ring adopts an envelope conformation, while the terminal benzene rings
      make a dihedral angle of 57.87 (9) degrees .

PMID- 22412653
TI  - 2,4-Bis(4-eth-oxy-phen-yl)-7-methyl-3-aza-bicyclo-[3.3.1]nonan-9-one.
AB  - The mol-ecule of the title compound, C(25)H(31)NO(3), exists in a twin-chair
      conformation with an equatorial orientation of the 4-eth-oxy-phenyl groups, as
      observed for its ortho isomer [Parthiban, Ramkumar, Park & Jeong (2011b ?), Acta
      Cryst. E67, o1475-o1476]. The methyl and 4-eth-oxy-phenyl groups are also
      equatorially oriented on the bicycle, as in the ortho analogue. In particular,
      although the cyclo-hexa-none ring deviates from an ideal chair, the piperidone
      ring is closer to an ideal chair, whereas in the ortho isomer both rings are
      significantly puckered and deviate from ideal chairs. The 4-eth-oxy-phenyl groups
      on both sides of the secondary amine group are oriented at an angle of 26.11 (3)
      degrees  with respect to each other, but the 2-eth-oxy-phenyl groups in the ortho
      isomer are oriented by less than half this [12.41 (4) degrees ]. In contrast to
      the absence of any significant inter-actions in the crystal packing of the ortho
      isomer, the title compound features N-H?O inter-actions, linking the mol-ecules
      along the b axis.

PMID- 22412654
TI  - 5,5'-[1,4-Phenyl-enebis(methyl-enesulfanedi-yl)]bis-[1,3,4-thia-diazol-2(3H)-one]
      dimethyl sulfoxide disolvate.
AB  - The asymmetric unit of the title compound, C(12)H(10)N(4)O(2)S(4).2C(2)H(6)OS,
      contains one half of the p-xylene mol-ecule and one dimethyl sulfoxide mol-ecule.
      The p-xylene mol-ecule is located about a crystallographic inversion centre. In
      the mol-ecule, the thia-diazole and benzene rings are almost perpendicular to one
      another, with a dihedral angle of 88.95 (6) degrees . In the crystal, an N-H?O
      hydrogen bond is observed between the two components. The dimethyl sulfoxide mol
      ecule is disordered over two orientations with an occupancy ratio of 0.879
      (1):0.121 (1).

PMID- 22412655
TI  - 1-Meth-oxy-4-({[(4-meth-oxy-phen-yl)-sulfan-yl](phen-yl)meth-yl}sulfan
      yl)benzene.
AB  - The title compound, C(21)H(20)O(2)S(2), forms a propeller-shaped structure with
      the tetra-hedral C atom as the central hub and meth-oxy-benzene and phenyl
      residues as radiating blades. Short C-H?pi contacts are observed.

PMID- 22412656
TI  - 6-Hydrazinylnicotinic acid: a powder study.
AB  - The structure of the title compound, C(6)H(7)N(3)O(2), is of inter-est with
      respect to radiopharmacueticals. The crystal packing is characterized by N-H?O
      and O-H?N hydrogen bonds, which form a three-dimensional network. The molecule is
      planar except for one of the amine H atoms.

PMID- 22412657
TI  - N-(2-Chloro-4-methyl-phen-yl)succinamic acid.
AB  - In the title compound, C(11)H(12)ClNO(3), the N-C=O fragment is twisted from the
      plane of the attached benzene ring by 48.39 (12) degrees . The carb-oxy-lic acid
      group is involved in O-H?O hydrogen bonding, which links pairs of mol-ecules into
      centrosymmetric dimers. N-H?O hydrogen bonds link these dimers, related by
      translation along the a axis, into ribbons.

PMID- 22412658
TI  - N-(3-Chloro-benzo-yl)-2-nitro-benzene-sulfonamide.
AB  - In the title compound, C(13)H(9)ClN(2)O(5)S, the N-C bond in the C-SO(2)-NH-C
      segment has a gauche torsion with respect to the S=O bonds. The conformation
      between the N-H bond and the ortho-nitro group in the sulfonyl benzene ring is
      syn, and that between the C=O and the meta-Cl atom in the benzoyl ring is anti.
      The mol-ecule is twisted at the S-N bond, with a torsion angle of 65.41 (38)
      degrees . The dihedral angle between the sulfonyl benzene ring and the -SO(2)-NH
      C-O segment is 75.0 (1) degrees , and that between the sulfonyl and the benzoyl
      benzene ring is 89.1 (1) degrees . The crystal structure features inversion
      related dimers linked by pairs of N-H?O(S) hydrogen bonds.

PMID- 22412659
TI  - 1,4-Dimethyl-piperazin-1-ium 3-hy-droxy-2-naphtho-ate.
AB  - The reaction of 1,4-dimethyl-piperazine and 3-hy-droxy-2-naphthoic acid gives the
      title 1:1 salt, C(6)H(15)N(2) (+).C(11)H(7)O(3) (-), with a singly protonated
      piperazinium cation. In the crystal, a single N-H?O hydrogen bond links the
      cations and anions into discrete pairs and the aromatic anions stack along the
      crystallographic a-axis direction. This results in layers of cations and anions
      alternating along the crystallographic c-axis direction. An intra-molecular O-H?O
      hydrogen bond is also present.

PMID- 22412660
TI  - 2-[(4-Bromo-phenyl-imino)-meth-yl]-4,6-di-iodo-phenol.
AB  - The title compound, C(13)H(8)BrI(2)NO, was prepared by the reaction of 3,5-diiodo
      salicyl-aldehyde with 4-bromo-phenyl-amine in ethanol. There is an intra
      molecular O-H?N hydrogen bond in the mol-ecule, which generates an S(6) ring. The
      dihedral angle between the benzene rings is 2.6 (3) degrees .

PMID- 22412661
TI  - 2,4-Diiodo-6-[(propyl-imino)-meth-yl]phenol.
AB  - The title compound, C(10)H(11)I(2)NO, was prepared by the reaction of 3,5-diiodo
      salicyl-aldehyde with propyl-amine in ethanol. The mol-ecule adopts an E
      conformation with respect to the C=N bond and the aromatic ring. The aromatic
      ring and the imino unit are close to being coplanar, with a dihedral angle of 2.6
      (3) degrees  between their planes. This planarity is assisted by the formation of
      an intra-molecular O-H?O hydrogen bond.

PMID- 22412662
TI  - (E)-1-(2,5-Dichloro-thio-phen-3-yl)ethan-one [8-(trifluoro-meth-yl)quinolin-4
      yl]hydrazone.
AB  - In the title compound, C(16)H(10)Cl(2)F(3)N(3)S, the dihedral angle between the
      quinoline and thio-phene ring systems is 4.94 (10) degrees . The NH group of the
      hydrazone moiety does not form a hydrogen bond, due to a steric crowding. In the
      crystal, the thio-phene ring takes part in weak pi-pi stacking inter-actions with
      the pyridine ring [centroid-to-centroid separation = 3.7553 (19) A and inter
      planar angle = 5.48 (12) degrees ] and the benzene ring [3.7927 (19) A and 4.58
      (12) degrees ]. Together, these lead to [100] stacks of mol-ecules in an
      alternating head-to-tail arrangement, with two pi-pi stacking contacts between
      each adjacent pair.

PMID- 22412663
TI  - (E)-6-Methyl-3-(2-methyl-benzyl-idene)-chroman-2-one.
AB  - In the title compound, C(18)H(16)O(2), the heterocyclic ring of the chroman-2-one
      system adopts a slightly distorted screw-boat conformation. The dihedral angle
      between the least-squares planes of the coumarin ring system and the benzene ring
      is 67.5 (1) degrees . The crystal packing features C-H?O hydrogen bonds, which
      link the mol-ecules into centrosymmetric R(2) (2)(8) dimers, and C-H?pi inter
      actions.

PMID- 22412664
TI  - 4-[3,5-Bis(2-hy-droxy-phen-yl)-1H-1,2,4-triazol-1-yl]benzoic acid dimethyl
      formamide monosolvate.
AB  - In the mol-ecule of deferasirox dimethyl-formamide solvate,
      C(21)H(15)N(3)O(4).C(3)H(7)NO, the central 1,2,4-triazole ring is tilted with
      respect to the benzoic acid and one of the 2-hy-droxy-phenyl units but coplanar
      with the other 2-hy-droxy-phenyl group, as indicated by the dihedral angles of
      33.69 (9), 72.57 (8) and 5.18 (9) degrees , respectively. Intra-molecular O-H?N
      hydrogen bonds generate an S(6) ring motif. In the crystal, deferasirox mol
      ecules are linked by O-H?N hydrogen bonds and weak C-H?O inter-actions into
      chains along the c axis. The dimethyl-formamide solvent mol-ecules are located
      between the deferasirox chains and are linked to the deferasirox mol-ecules by O
      H?O hydrogen bonds and weak C-H?O inter-actions.

PMID- 22412665
TI  - (2Z)-1-(5-Hy-droxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-3-(4-methyl-anilino)-but-2
      en-1-one.
AB  - A twist is evident in the title compound, C(21)H(21)N(3)O(2), the dihedral angle
      between the terminal six-membered rings being 29.46 (10) degrees ; the linked
      five- and six-membered rings are coplanar [1.30 (11) degrees ]. The carbonyl O
      atom accepts intra-molecular hydrogen bonds from the adjacent hy-droxy and amine
      groups. The three-dimensional crystal packing is achieved through C-H?pi inter
      actions.

PMID- 22412666
TI  - 2-(Adamantan-1-yl)-5-(4-nitro-phen-yl)-1,3,4-oxadiazole.
AB  - The title mol-ecule, C(18)H(19)N(3)O(3), lies on a mirror plane that bis-ects the
      adamantyl group. In the crystal, C-H?O and C-H?N inter-actions lead to supra
      molecular chains along [100]. These assemble into layers in the ab plane via pi
      pi inter-actions [centroid-centroid distance = 3.6548 (7) A] between the
      oxadiazole and benzene rings.

PMID- 22412667
TI  - 2-[(E)-Phen-yl(2-phenyl-hydrazin-1-yl-idene)meth-yl]phenol.
AB  - In the title hydrazone derivative, C(19)H(16)N(2)O, a twist is found between the
      hy-droxy-phenyl and N-bound phenyl rings [dihedral angle = 24.37 (7) degrees ].
      The C-bound phenyl ring is almost perpendicular to each of these planes [dihedral
      angles = 75.30 (7) and 86.00 (7) degrees , respectively]. The conformation about
      the imine bond [1.2935 (17) A] is E. The hy-droxy group forms an intra-molecular
      hydrogen bond with the imine N atom. Zigzag chains along [001] mediated by N-H?O
      hydrogen bonds feature in the crystal packing.

PMID- 22412668
TI  - Ethyl (E)-3-hy-droxy-2-[(4-meth-oxy-styr-yl)-carbamo-yl]but-2-enoate.
AB  - The title compound, C(16)H(19)NO(5), which was synthesized from p-meth-oxy
      cinnamic acid, has intra-molecular O-H?O and N-H?O hydrogen-bonding inter
      actions. In the crystal, mol-ecules are linked by weak C-H?O hydrogen bonds and
      aromatic pi-pi stacking inter-actions [minimum ring centroid-centroid separation
      = 3.790 (1) A].

PMID- 22412669
TI  - 2-(4-Chloro-phen-yl)-1-phenyl-1H-benz-imidazole.
AB  - In the title compound, C(19)H(13)ClN(2), the dihedral angle formed by the
      imidazole core with the chloro-phenyl and phenyl rings are 24.07 (4) and 67.24
      (4) degrees , respectively.

PMID- 22412670
TI  - 1-(2-Hy-droxy-eth-yl)-1'-methyl-4'-(naph-thal-en-1-yl)-1'',2'',3'',4''-tetra
      hydro-dispiro-[indoline-3,2'-pyrrolidine-3',2''-naphthalene]-2,1''-dione.
AB  - In the title compound, C(33)H(30)N(2)O(3), the pyrrolidine ring adopts an
      envelope conformation in which the H atom attached the an ortho-C atom deviates
      from the plane, whereas the cyclo-hexa-none ring in the tetra-hydro-naphthalene
      fused-ring system adopts a sofa conformation. The oxindoline ring system is
      almost perpendicular with respect to the mean plane of the pyrrolidine ring, with
      a dihedral angle of 89.0 (1) degrees . Five intra-molecular C-H?O close contacts
      are observed. In the crystal, mol-ecules associate via O-H?O hydrogen bonds,
      forming R(2) (2)(14) dimers. In addition, there are weak C-H?pi inter-actions.

PMID- 22412671
TI  - (3E,5E)-3,5-Bis(naphthalen-1-yl-methyl-idene)piperidin-4-one.
AB  - In the title compound, C(27)H(21)NO, the piperidine ring adopts a chair
      conformation. The mean plane through the piperidine ring makes dihedral angles of
      49.27 (5) and 63.07 (5) degrees  with the naphthalene ring systems. In the
      crystal, mol-ecules are linked into dimers via pairs of inter-molecular C-H?O
      inter-actions, generating ten-membered R(2) (2)(10) ring motifs. C-H?pi inter
      actions further stabilize the crystal structure.

PMID- 22412672
TI  - (6,6'-Dimeth-oxy-biphenyl-2,2'-di-yl)bis(diphenyl-phosphane) P,P'-dioxide
      dihydrate.
AB  - In the title compound, C(38)H(32)O(4)P(2).2H(2)O, the dihedral angle between the
      meth-oxy-phenol rings is 84.11 (7) degrees . O-H?O hydrogen bonds connect the
      water mol-ecules of crystallization with the main mol-ecule.

PMID- 22412673
TI  - 10,16-Dichloro-6,20-dioxa-3,23-diaza-tetra-cyclo-[23.3.1.0.0]nona-cosa
      1(29),7,9,11,14(19),15,17,25,27-nona-ene-4,22-dione methanol monosolvate.
AB  - In the title compound, C(25)H(22)Cl(2)N(2)O(4).CH(3)OH, the macrocyclic mol-ecule
      adopts a slightly distorted C(2)-symmetric conformation. The macrocyclic mol
      ecules are linked via N-H?O hydrogen bonds between the amide groups into chains
      extending along the [010] direction. The methanol mol-ecules bridge these chains
      via N-H?O and O-H?O hydrogen bonds with the formation of a two-dimensional
      polymeric structure parallel to (001). The methanol mol-ecule is disordered over
      two positions with the occupancy ratio of 9:1. The disorder of the solvent
      molecule is caused by weak intermolecular C-H?Cl hydrogen bonding.

PMID- 22412674
TI  - 2-[3,5-Bis-(4-fluoro-phen-yl)-4,5-dihydro-1H-pyrazol-1-yl]-4,6-bis(4-fluoro
      phenyl)pyrimidine.
AB  - In the title compound, C(31)H(20)F(4)N(4), the pyrazole ring adopts an envelope
      conformation and forms a dihedral angle of 9.91 (6) degrees  with the adjacent
      pyrimidine ring. The pyrimidine ring forms dihedral angles of 9.23 (6) and 2.16
      (5) degrees  with its adjacent fluoro-substituted benzene rings, whereas these
      angles are 88.22 (6) and 9.66 (6) degrees  for the pyrazole ring and its adjacent
      benzene rings. In the crystal, mol-ecules are linked by C-H?F hydrogen bonds into
      ribbons along [01-1]. The crystal packing is further stabilized by C-H?pi and by
      pi-pi inter-actions, with centroid-centroid distances of 3.7428 (7) and 3.7630
      (6) A.

PMID- 22412675
TI  - Bis[(2,2-dimethyl-propano-yloxy)meth-yl] {[2-(6-amino-9H-purin-9-yl)eth-oxy]meth
      yl}phospho-nate-succinic acid (2/1).
AB  - The title compound, C(20)H(32)N(5)O(8)P.0.5C(4)H(6)O(4), is composed of two 9-{2
      [bis-(pivaloyloxymeth-oxy)phosphinylmeth-oxy]eth-yl}adenine, commonly known as
      adefovir dipivoxil (AD), mol-ecules linked to the carb-oxy-lic acid groups of
      succinic acid (SA). The asymmetric unit contains one mol-ecule of AD and half a
      mol-ecule of SA, which sits on an inversion center. Both adenine units in the two
      AD mol-ecules make AD-SA N-H?O and SA-AD O-H?N hydrogen bonds to SA. In addition,
      the inter-molecular AD-AD N-H?O-P hydrogen bond serves to stabilize the
      cocrystal. There is also a pi-pi stacking inter-action [inter-planar spacing 3.34
      (19) A] between adjacent inversion-related adenine groups.

PMID- 22412676
TI  - N,N'-(1,4-Phenyl-ene)bis-(2-bromo-2-methyl-propanamide).
AB  - The mol-ecular structure of the title compound, C(14)H(18)Br(2)N(2)O(2), has one
      half-mol-ecule in the asymmetric unit. The mol-ecule has a crystallographic
      inversion centre in the middle of the benzene ring. The C-C-N-C torsion angle
      between the benzene ring and the bromo-amide group is 149.2 (7) degrees . The
      crystal is stabilized by a strong inter-molecular N-H?O bond and weak C-H?O inter
      actions. These contacts give rise to a three-dimensional network.

PMID- 22412677
TI  - 1-[(4-Bromo-phen-yl)(morpholin-4-yl)-meth-yl]naphthalen-2-ol.
AB  - The title compound, C(21)H(20)BrNO(2), was obtained via a one-pot synthesis from
      the reaction of 4-bromo-benzaldehyde, 2-naphthol and morpholine. In the
      asymmetric unit, there are four mol-ecules with similar structures. The
      morpholine ring adopts a chair conformation, and the hy-droxy group links with
      the morpholine via an intra-molecular O-H?N hydrogen bond. The bromo-phenyl ring
      is approximately perpendicular to the mean pane of the naphthalene system at
      dihedral angles of 76.7 (3), 81.4 (3), 79.7 (3) and 84.5 (3) degrees  in the four
      independent mol-ecules. Weak C-H?O hydrogen bonds are observed in the crystal.

PMID- 22412678
TI  - (2Z)-3-(3-Bromo-anilino)-1-(5-hy-droxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)but-2-en
      1-one.
AB  - In the title compound, C(20)H(18)BrN(3)O(2), the central carbonyl group forms
      amine-N-H?O and hy-droxy-O-H?O hydrogen bonds, which lead to two fused S(6)
      rings. The N-bound phenyl ring is coplanar with the five-membered ring to which
      it is attached [dihedral angle = 5.22 (18) degrees ], but the dihedral angle
      [33.87 (17) degrees ] between the terminal phenyl and bromo-benzene rings
      indicates an overall twist in the mol-ecule. In the crystal packing, mol-ecules
      assemble into dimeric aggregates via C-H?pi inter-actions.

PMID- 22412679
TI  - (2E)-2-[(2E)-3-Phenyl-prop-2-en-1-yl-idene]-2,3-dihydro-1H-inden-1-one.
AB  - The title indan-1-one derivative, C(18)H(14)O, is planar with an r.m.s. deviation
      for all 19 non-H atoms of 0.098 A. The conformation about each of the C=C bonds
      [1.343 (3) and 1.349 (3) A] is E. Supra-molecular layers in the bc plane,
      mediated by C-H?O and pi-pi [ring centroid-centroid distance = 3.5282 (15) A]
      inter-actions, feature in the crystal packing.

PMID- 22412680
TI  - (2E)-2-(4-Meth-oxy-benzyl-idene)-2,3-di-hydro-1H-inden-1-one.
AB  - In the title compound, C(17)H(14)O(2), the indan-1-one system is almost planar
      (r.m.s. deviation = 0.007 A) and the benzene ring is twisted out of its plane by
      8.15 (6) degrees . The conformation about the C=C double bond [1.348 (2) A] is E.
      Helical supra-molecular chains along [010] feature in the crystal packing; these
      are sustained by C-H?O hydrogen bonds and pi-pi inter-actions between
      translationally related indan-1-one systems [centroid-centroid distance = 3.7970
      (10) A].

PMID- 22412681
TI  - 2-(8-Bromo-imidazo[1,2-a]pyridin-2-yl)-N'-[(E)-4-diethyl-amino-2-hy-droxy-benzyl
      idene]acetohydrazide dihydrate.
AB  - In the title compound, C(20)H(22)BrN(5)O(2).2H(2)O, the Schiff base mol-ecule
      exists in an E conformation with respect to the acyclic C=N bond. An S(6) ring
      motif is formed via an intra-molecular O-H?N hydrogen bond. The dihedral angle
      between the imidazo[1,2-a]pyridine system and the benzene ring is 84.62 (5)
      degrees . In the crystal, N-H?O, O-H?O, O-H?N, C-H?O and C-H?Br hydrogen bonds
      link the mol-ecules into a three-dimensional network. The crystal packing is
      further stabilized by C-H?pi and pi-pi inter-actions [centroid-centroid distance
      = 3.5365 (7) A].

PMID- 22412682
TI  - 1-[5-(4-Chloro-phen-yl)-3-(4-hy-droxy-phen-yl)-4,5-dihydro-1H-pyrazol-1-yl]
      ethanone.
AB  - In the title compound, C(17)H(15)ClN(2)O(2), the benzene rings form dihedral
      angles of 89.56 (5) and 5.87 (5) degrees  with the mean plane of the pyrazoline
      ring (r.m.s. deviation = 0.084 A). The dihedral angle between the two benzene
      rings is 87.57 (5) degrees . In the crystal, mol-ecules are linked by O-H?O and C
      H?O hydrogen bonds into a helical chain along the c axis. Between the chains weak
      C-H?N and C-H?O inter-actions are present. The crystal studied was an inversion
      twin with a domain ratio of 0.72 (4):0.28 (4).

PMID- 22412683
TI  - N-(4-Methyl-2-nitro-phen-yl)succinamic acid.
AB  - In the title compound, C(11)H(12)N(2)O(5), the conformation of the N-H bond in
      the amide segment is syn to the ortho-nitro group in the benzene ring. The amide
      C=O and the carboxyl C=O of the acid segment are syn to each other and both are
      anti to the H atoms on the adjacent -CH(2) groups. Furthermore, the C=O and O-H
      bonds of the acid group are in syn positions with respect to each other. The
      dihedral angle between the benzene ring and the amide group is 36.1 (1) degrees .
      The amide H atom shows bifurcated intra-molecular hydrogen bonding with an O atom
      of the ortho-nitro group and an inter-molecular hydrogen bond with the carbonyl O
      atom of another mol-ecule. In the crystal, the N-H?O(C) hydrogen bonds generate a
      chain running along the [100] direction. Inversion dimers are formed via a pair
      of O-H?O(C) interactions, that form an eight-membered hydrogen-bonded ring
      involving the carboxyl group.

PMID- 22412684
TI  - 4-Chloro-N-(3,5-dimethyl-phen-yl)benzamide.
AB  - In the mol-ecular structure of the title compound, C(15)H(14)ClNO, the amide
      group forms dihedral angles of 15.8 (2) and 27.2 (2) degrees , respectively, with
      the benzoyl and aniline rings, while the angle between the benzoyl and aniline
      rings is 11.5 (1) degrees . The crystal structure is stabilized by N-H?O hydrogen
      bonds, which give rise to infinite chains running along the c axis.

PMID- 22412685
TI  - 5-Methyl-3,3-bis-(morpholin-4-yl)-1-[2-(morpholin-4-yl)eth-yl]-2,3-dihydro-1H
      indol-2-one.
AB  - In the title compound, C(23)H(34)N(4)O(4), the morpholine rings adopt chair
      conformations. The N atom of the indol-2-one group is linked to the N atom of one
      morpholine ring through a flexible ethyl group with an almost cif conformation.
      In the crystal, molecules are linked by C-H?O interactions into infinite chains
      along the c direction. The almost parallel infinite chains are further inter
      connected via other sets of C-H?O inter-actions, forming a three-dimensional
      framework.

PMID- 22412686
TI  - 7-Benzyl-3-(4-chloro-phen-yl)-2-isobutyl-amino-5,6,7,8-tetra-hydro
      pyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3H)-one.
AB  - In the title compound, C(26)H(27)ClN(4)OS, the thienopyrimidine fused-ring system
      is close to coplanar (r.m.s. deviation = 0.0089 A), with a maximum deviation of
      0.0283 (17) A for the N atom adjacent to the benzene ring. This ring system forms
      dihedral angles of 83.51 (3) and 88.20 (5) degrees  with the adjacent benzyl and
      phenyl rings, respectively. In the crystal, N-H?Cl inter-actions and C-H?O
      hydrogen bonds are observed.

PMID- 22412687
TI  - 2-Amino-4-(2-chloro-phen-yl)-7,7-di-methyl-5-oxo-5,6,7,8-tetra-hydro-4H-chromene
      3-carbonitrile hemihydrate.
AB  - The asymmetric unit of the title compound, C(18)H(17)ClN(2)O(2).0.5H(2)O,
      contains two organic mol-ecules and one solvent water mol-ecule. In each organic
      mol-ecule, the cyclo-hexene ring adopts an envelope conformation with the C atom
      connecting the two methyl groups on the flap; the 4H-pyran ring is nearly planar
      [maximum deviation = 0.113 (3) A in one mol-ecule and 0.089 (3) A in the other
      mol-ecule] and is approximately perpendicular to the chloro-phenyl ring [dihedral
      angle = 86.43 (15) degrees  in one mol-ecule and 89.73 (15) degrees  in the other
      mol-ecule]. Inter-molecular N-H?N, N-H?O, O-H?O and O-H?Cl hydrogen bonding is
      present in the crystal.

PMID- 22412688
TI  - 4-(4-Chloro-phen-yl)-3-cyano-7-(4-meth-oxy-phen-yl)-5-oxo-5,6,7,8-tetra-hydro-4H
      chromen-2-aminium methano-late.
AB  - In the cation of the title organic ion pair compound, C(23)H(20)ClN(2)O(3)
      (+).CH(3)O(-), the cyclo-hexyl ring shows a half-boat conformation and the
      dihedral angles between two benzene rings and the pyran ring are 83.14 (7) and
      73.18 (9) degrees . In the crystal, centrosymmetrically related cations are
      linked into a dimer by pairs of N-H?N hydrogen bonds, generating an R(2) (2)(12)
      ring motif. The anion inter-acts with the dimer through an N-H?O hydrogen bond.
      pi-pi inter-actions between pyran rings of adjacent dimers, with a centroid
      centroid distance of 3.861 (2) A, are also observed.

PMID- 22412689
TI  - 2,3,4-Trihy-droxy-benzoic acid 0.25-hydrate.
AB  - The asymmetric unit of the title compound, C(7)H(6)O(5).0.25H(2)O, contains two
      mol-ecules of 2,3,4-trihy-droxy-benzoic acid, with similar conformations, and one
      water mol-ecule which lies on a twofold rotation axis. Both acid mol-ecules are
      essentially planar [maximum r.m.s deviations = 0.0324 (2) and 0.0542 (3) A for
      the two acid molecules]. The mol-ecular conformations are stabilized by intra
      molecular O(phenol)-H?O(carbox-yl/phenol) inter-actions. A cyclic inter-molecular
      association is formed between the two acid and one water mol-ecule [graph set
      R(3) (3)(12)] involving O-H?O hydrogen bonds. The two acid mol-ecules are further
      linked through a cyclic R(2) (2)(8) carb-oxy-lic acid hydrogen-bonding
      association, which together with inter-molecular O-H?O hydrogen-bonding inter
      actions involving the phenol groups and the water mol-ecule, and weak pi-pi inter
      actions [minimum ring centroid separation = 3.731 (3) A], give a three
      dimensional network.

PMID- 22412690
TI  - Methyl-naltrexone bromide methanol monosolvate.
AB  - IN THE TITLE COMPOUND [SYSTEMATIC NAME: (4R,4aS,7aR,12bS)-3-cyclo-propyl-meth-yl
      4a,9-hy-droxy-7-oxo-2,3,4,4a,5,6,7,7a-octa-hydro-1H-4,12-methano-benzofuro[3,2
      e]isoquinolin-3-ium bromide methanol monosolvate], C(21)H(26)NO(4) (+).Br(
      ).CH(3)OH, two of the three six-membered rings adopt chair conformations while
      the third, which contains a C=C double bond, adopts an approximate half-boat
      conformation. The 2,3-dihydro-furan ring adopts an envelope conformation. In the
      crystal, the components are linked by O-H?O and O-H?Br hydrogen bonds. The
      absolute stereochemistry was inferred from one of the starting materials.

PMID- 22412691
TI  - 9-Ethynyl-9H-carbazole.
AB  - The title compound, C(14)H(9)N, is the second crystallographically characterized
      example of an ynamine with an H atom in the C-terminal position. There are two
      independent mol-ecules (A and B) in the asymmetric unit. The structures of both
      mol-ecules are essentially planar (r.m.s. deviation = 0.0312 and 0.0152 A). The N
      C(sp) bond lengths are 1.353 (4) and 1.350 (4) A, and those of the acetyl-ene
      bonds are 1.189 (4) and 1.190 (4) A. The C(sp)-H bond lengths are 0.95 (5) and
      0.97 (4) A. These geometries are consistent with those of the previously reported
      ynamine characterized by crystallography. In the crystal, the mol-ecules stack
      along the c axis, forming two kinds of columnar structures. The acetyl-ene C
      atoms of mol-ecule A have a short contact [3.341 (4) A and 3.396 (4) A] with an
      adjacent mol-ecule A at the C-C bond of the fused part, which originates in pi-pi
      stacking inter-action; no remarkable spatial contact is recognized within the
      stacking of mol-ecule B.

PMID- 22412692
TI  - 3-Carb-oxy-quinolin-1-ium-2-carboxyl-ate monohydrate.
AB  - The title compound, C(11)H(7)NO(4).H(2)O, contains a 3-carb-oxy-quinolin-1-ium-2
      carboxyl-ate (qda) zwitterion and one water mol-ecule. In the crystal, pairs of N
      H?O hydrogen bonds link the mol-ecules into inversion dimers, and these dimers
      are further connected by O-H?O hydrogen bonds into a three-dimensional supra
      molecular architecture. In addition, pi-pi inter-actions occur between pyridine
      and benzene rings from different qda ligands [centroid-centroid distance = 3.749
      (1) A] and the dihedral angles of the -CO(2)H and -CO(2) groups to the quinoline
      system are 8.47 (3) and 88.16 (6) degrees , respectively.

PMID- 22412693
TI  - 5-(4-Eth-oxy-phen-yl)-3-(pyridin-2-yl)-4,5-dihydro-1H-pyrazole-1-carbothio-amide.
AB  - In the title compound, C(17)H(18)N(4)OS, a pyrazoline derivative, the pyrazoline
      ring adopts an envelope conformation with the C atom bonded to the benzene ring
      as the flap atom. The dihedral angle between the pyridine and benzene rings is
      80.50 (6) degrees . The eth-oxy-phenyl group is approximately planar, with an
      r.m.s. deviation of 0.0238 (1) A for the nine non-H atoms. In the crystal, mol
      ecules are linked by N-H?O and N-H?S hydrogen bonds into a tape along the b axis.
      Weak C-H?N and C-H?pi inter-actions are also observed.

PMID- 22412694
TI  - (3S,11Z)-14,16-Dihy-droxy-3-methyl-3,4,5,6,9,10-hexa-hydro-1H-2-benz-oxacyclo
      tetra-decine-1,7(8H)-dione (cis-zearalenone): a redetermination.
AB  - The title compound, also known as cis-zearalenone (cis-ZEN), C(18)H(22)O(5), has
      already been reported elsewhere [Griffin et al. (1981 ?). ACA Ser.29, 35], but no
      atomic coordinates are publicly available. The mol-ecule is of inter-est with
      respect to its toxicity. In the crystal, intra-molecular O-H?O hydrogen bonds
      stabilize the mol-ecular conformation, while inter-molecular O-H?O hydrogen bonds
      link the mol-ecules to form infinite chains along the [110] and [1-10]
      directions. The absolute configuration has been assigned by reference to an
      unchanging chiral centre in the synthetic procedure.

PMID- 22412695
TI  - 5-Amino-4-bromo-2,3-dihydro-1H-inden-1-one.
AB  - In the title compound, C(9)H(8)BrNO, the non-H-atom framework is essentially
      planar, with a maximum deviation of 0.087 (3) A. In the crystal, mol-ecules are
      inter-connected into a three-dimensional network by C-H?O and N-H?O hydrogen
      bonds. In addition, C-H?pi inter-actions and a pi-pi stacking inter-action, with
      a centroid-centroid distance of 3.5535 (19) A, are also observed.

PMID- 22412696
TI  - Dimethyl 4,5-dichlorobenzene-1,2-dicarboxyl-ate.
AB  - In the title compound, C(10)H(8)Cl(2)O(4), the two Cl atoms and one of the meth
      oxy-carbonyl groups are almost coplanar [maxi-mum derivation = 0.035 (2) A] with
      the benzene plane, and the other meth-oxy-carbonyl group exhibits an almost
      orthogonal disposition relative to the benzene plane, with a dihedral angle of
      84.82 (3) degrees  between the planes. In the crystal, the molecules are
      connected into a chain propagating along the [011] direction through nonclassical
      C-H?O hydrogen bonds.

PMID- 22412697
TI  - N-(3-Chloro-4-methyl-phen-yl)succinamic acid.
AB  - In the crystal structure of the title compound, C(11)H(12)ClNO(3), the asymmetric
      unit contains two independent mol-ecules. The N-H bond in the amide segment is
      anti to the meta-Cl atom in the benzene ring, in both molecules. The amide and
      carboxyl C=O bonds are also anti to each other and anti to the H atoms on the
      adjacent -CH(2) groups. Furthermore, the C=O and O-H bonds of the acid group are
      in syn positions with respect to each other. The dihedral angles between the
      benzene ring and the amide group are 40.6 (2) and 44.9 (3) degrees  in the two
      independent molecules. In the crystal, mol-ecules are packed into sheets parallel
      to the (11-3) plane through O-H?O and N-H?O hydrogen bonds.

PMID- 22412698
TI  - (2E)-2-(5-Bromo-2-hy-droxy-3-meth-oxy-benzyl-idene)-N-cyclo-hexyl-hydrazine
      carbothio-amide.
AB  - The title compound, C(15)H(20)BrN(3)O(2)S, crystallizes in the thio-amide form
      and adopts an E,E conformation with respect to the azomethine and hydrazinic
      bonds, respectively. The mol-ecules are paired through N-H?O and O-H?S hydrogen
      bonds, leading to the formation of centrosymmetric dimers in the crystal. These
      dimers are stacked along the a axis and are inter-connected through N-H?S
      hydrogen bonds to generate polymeric chains. The structure also features C-H?pi
      interactions. An intra-molecular O-H?O bond is also present.

PMID- 22412699
TI  - 1,5-Diamino-2,6-dibromo-9,10-anthraquinone.
AB  - In the title compound, C(14)H(8)Br(2)N(2)O(2), the mol-ecular structure features
      intra-molecular N-H?O [2.639 (2) A and 130 degrees ] and N-H?Br [3.053 (2) A and
      114 degrees ] hydrogen bonding. Due to inversion symmetry, the asymmetric part of
      the unit cell consits of one half-mol-ecule. In the crystal, inversion dimers
      linked by pairs of N-H?O [2.955 (2) A and 135 degrees ] hydrogen bonds occur. The
      structure also features C=O?pi [3.228 (2) A] and Br?Br [3.569 (1) A] contacts.

PMID- 22412700
TI  - 1-[5-(2-Chloro-phen-yl)-5-hy-droxy-3-methyl-4,5-dihydro-1H-pyrazol-1-yl]
      ethanone.
AB  - The title compound, C(12)H(13)ClN(2)O(2), crystallizes with two independent but
      very similar mol-ecules (A and B) in the asymmetric unit. The pyrazole ring in
      each mol-ecule has an envelope conformation. The dihedral angle between the
      pyrazole ring mean plane and the benzene ring is 86.07 (14) degrees  in A and
      85.99 (14) degrees  in B. In the crystal, the A and B mol-ecules are linked via a
      pair of O-H?O hydrogen bonds, forming dimers. These dimers are further linked via
      C-H?O inter-actions to form -A-B-A-B- chains propagating along the c-axis
      direction.

PMID- 22412701
TI  - 4-Benzyl-4-ethyl-morpholin-1-ium hexa-fluoro-phosphate.
AB  - The asymmetric unit of the title compound, C(13)H(20)NO(+).PF(6) (-), contains
      two cations, one complete anion and two half hexa-fluoro-phosphate anions having
      crystallographically imposed twofold rotation symmetry. In the cations, the
      morpholine rings are in a chair conformation. In the crystal, ions are linked by
      weak C-H?F hydrogen bonds into a three-dimensional network.

PMID- 22412702
TI  - 2-[(2-Chloro-phen-yl)imino-meth-yl]-4,6-di-iodo-phenol.
AB  - The asymmetric unit of the title compound, C(13)H(8)ClI(2)NO, contains half of
      the mol-ecule situated on a mirror plane. The hy-droxy group is involved in the
      formation of an intra-molecular O-H?N hydrogen bond. pi-pi inter-actions between
      the benzene rings of neighbouring mol-ecules [centroid-centroid distance = 3.629
      (3) A] form stacks along the b axis. In the crystal, weak C-H?O and C-H?Cl inter
      actions are observed.

PMID- 22412703
TI  - Diethyl 2,2'-bis-(hy-droxy-imino)-3,3'-(hydrazinediyl-idene)dibutano-ate.
AB  - Each mol-ecule of the title compound, C(12)H(18)N(4)O(6), is located on an
      inversion centre at the mid-point of the central N-N bond. The azo groups C=N of
      the Schiff base group have an E conformation and the azo groups in the oxime C=N
      O groups have a Z conformation. O-H?O hydrogen bonds link neighbouring mol-ecules
      into infinite monolayers perpendicular to the a axis.

PMID- 22412704
TI  - 2,6-Dichloro-N-(4-chloro-phen-yl)benzamide.
AB  - In the title compound, C(13)H(8)Cl(3)NO, the dihedral angle between the benzene
      rings is 63.2 (2) degrees . In the crystal, N-H?O hydrogen bonds link the mol
      ecules into C(4) chains propagating in [001]. Weak aromatic pi-pi stacking also
      occurs [centroid-centroid separations = 3.759 (3) and 3.776 (3) A].

PMID- 22412705
TI  - 3-Hy-droxy-2,2-bis-(1H-pyrazol-1-yl)-cyclo-penta-none.
AB  - The title compound, C(11)H(12)N(4)O(2), was unexpectedly obtained in the reaction
      of alpha,alpha'-disubstituted cyclo-penta-none with 1,1,3,3-tetra-meth-oxy
      propane in the presence of dioxane saturated with HCl. It belongs to a previously
      unknown class of gem-bihetaryl ketones which may be useful for screening of new
      substances with biological activity. In the studied structure, the cyclo-penta
      none moiety adopts an envelope conformation, with the hy-droxy-bearing C atom as
      the flap [deviation from basal plane = 0.643 (3) A]. The dihedral angle between
      the two pyrazole rings is 80.02 (8) degrees . In the crystal, inversion dimers
      are formed via a pair of O-H?N hydrogen bonds.

PMID- 22412706
TI  - 3,3'-[1,4-Phenyl-enebis(methyl-ene)]-bis-(1-propyl-benzimidazolium) dichloride
      dihydrate.
AB  - The asymmetric unit of the title compound, C(28)H(32)N(4) (2+).2Cl(-).2H(2)O,
      contains half of a 3,3'-[1,4-phenyl-enebis(methyl-ene)]bis-(1-propyl
      benzimidazolium) cation, one chloride anion and one water mol-ecule. The complete
      cation is generated by a crystallographic inversion center. The central benzene
      ring forms a dihedral angle of 66.06 (11) degrees  with its adjacent
      benzimidazolium ring system. In the crystal, the cations, anions and water mol
      ecules are linked by O-H?Cl, C-H?O and C-H?Cl hydrogen bonds into a three
      dimensional network. The crystal packing is further stabilized by pi-pi inter
      actions, with centroid-centroid distances of 3.5561 (15) and 3.6708 (15) A.

PMID- 22412707
TI  - (3Z,3'Z)-3,3'-(3,5-Dimethyl-furan-2,4-diyl)bis-(4-hy-droxy-pent-3-en-2-one).
AB  - In the title mol-ecule, C(16)H(20)O(5), the two 4-hy-droxy-pent-3-en-2-one units
      are essentially planar, with r.m.s. deviations of 0.0183 (2) and 0.0134 (2) A for
      the non-H atoms, and make dihedral angles of 81.20 (10) and 84.44 (10) degrees 
      with the central furan ring. The dihedral angle between these two side units is
      22.06 (9) degrees . Two intra-molecular O-H?O hydrogen bonds generate two S(6)
      ring motifs. A weak inter-molecular C-H?O inter-action is also observed.

PMID- 22412708
TI  - (E)-N'-(3-Eth-oxy-4-hy-droxy-benzyl-idene)-4-meth-oxy-benzohydrazide.
AB  - In the mol-ecule of the title benzohydrazide derivative, C(17)H(18)N(2)O(4), the
      dihedral angle between the benzene rings is 6.86 (11) degrees . The meth-oxy
      group of the 4-meth-oxy-phenyl fragment deviates slightly [C(methyl)-O-C-C = 10.0
      (4) degrees ] with respect to the benzene ring, whereas the eth-oxy group of the
      3-eth-oxy-4-hy-droxy-phenyl fragment is is almost coplanar [C-O-C-C(methyl) =
      178.5 (2) degrees ]. In the crystal, mol-ecules are linked by N-H?O, O-H?O and C
      H?O hydrogen bonds into a two-dimensional network parallel to the ab plane. C
      H?pi inter-actions and C?O [2.980 (3) A] short contacts are also observed.

PMID- 22412709
TI  - 2-(4-Methyl-phen-yl)-5-[({[5-(4-methyl-phen-yl)-1,3,4-thia-diazol-2-yl]sulfan
      yl}meth-yl)sulfan-yl]-1,3,4-thia-diazole.
AB  - In the title compound, C(19)H(16)N(4)S(4), the mol-ecules exhibit a butterfly
      conformation, where the thia-diazole and attached benzene rings in two wings are
      almost coplanar, with dihedral angles of 0.8 (3) and 0.9 (3) degrees ,
      respectively, while the two thia-diazole rings form a dihedral angle of 46.3 (3)
      degrees .

PMID- 22412710
TI  - 4-Bromo-2-meth-oxy-6-(1-phenyl-1H-benzimidazol-2-yl)phenol.
AB  - The title compound, C(20)H(15)BrN(2)O(2), crystallized with three independent
      molecules in the asymmetric unit. Intramolecular O-H?N hydrogen bonds induce
      coplanarity of the substituted benzene ring and the benzimidazole ring, with mean
      deviations from the planes of 0.0931 (10), 0.0448 (10) and 0.0083 (11) A in the
      three mol-ecules.

PMID- 22412711
TI  - 2-(3-Amino-pyridinium-1-yl)-3-carb-oxy-propano-ate monohydrate.
AB  - The title compound, C(9)H(10)N(2)O(4).H(2)O, was obtained as a zwitterion derived
      from the nucleophilic attack of 3-amino-pyridine on the fumaric alpha,beta
      system. Within the molecule, the amino-pyridine moiety and the carboxyl-ate and
      carb-oxy-lic acid fragments form dihedral angles of 68.6 (2) and 62.8 (2) degrees
      , respectively. The geometry adopted by the mol-ecule does not allow the
      formation of centrosymmetric dimeric hydrogen-bonded units; instead chains along
      the a axis are linked by COO-H?OOC motifs. These chains are inter-connected by N
      H?O and O-H?O hydrogen bonds involving the carb-oxy-lic acid and carboxyl-ate
      units and the solvent water mol-ecules.

PMID- 22412712
TI  - 1-[(Z)-2-Butyl-tellan-yl-1-chloro-ethen-yl]-cyclo-hex-1-ene.
AB  - The Te(II) atom in the title mol-ecule, C(12)H(19)ClTe, is coordinated in a V
      shaped geometry by C atoms derived from the disparate organic substituents. A
      short intramolecular C-H?Cl contact occurs owing to the proximity of the ethene
      bond in the six-membered ring to the Cl atom. In the crystal, mol-ecules assemble
      into layers parallel to the ac plane, with the closest inter-actions between them
      being of the Te?Te type [3.9993 (16) A].

PMID- 22412713
TI  - 2,2'-Dimethyl-1,1'-[2,2-bis-(bromo-methyl)propane-1,3-di-yl]dibenzimidazole
      hemihydrate.
AB  - The title compound, C(21)H(22)Br(2)N(4).0.5H(2)O, contains two benzimidazole
      groups which may provide two potential coordination nodes for the construction of
      metal-organic frameworks. The mean planes of the two imidazole groups are almost
      perpendicular, with a dihedral angle of 83.05 (2) degrees , and adjacent mol
      ecules are linked into a one-dimensional chain by pi-pi stacking inter-actions
      between imidazole groups of different mol-ecules [centroid-to-centroid distances
      of 3.834 (2) and 3.522 (2) A].

PMID- 22412714
TI  - 2,2'-[(2S*,6R*)-Piperidine-2,6-di-yl]-di-pro-pan-2-ol.
AB  - In the title compound, C(11)H(23)NO(2), the piperidine ring has a chair
      conformation. The two hy-droxy H atoms are disordered over two positions with
      fixed occupancy ratios of 0.57:0.43 and 0.63:0.37. In the mol-ecule, there are
      two short N-H?O inter-actions. In the crystal, four symmetry-related mol-ecules
      are linked by O-H?O hydrogen bonds to form a cage-like arrangement, centered
      about the point of inter-section of three twofold axes. These cages stack along
      the [100] direction.

PMID- 22412715
TI  - 7'-(Naphthalen-1-yl)-5''-[(naphthalen-2-yl)-methyl-idene]-1',3',5',6',7',7a'-hexa
      hydro-dispiro-[acenaphthene-1,5'-pyrrolo-[1,2-c]thia-zole-6',3''-piperidine]
      2(1H),4''-dione.
AB  - In the title compound, C(43)H(34)N(2)O(2)S, the six-membered piperidine ring
      adopts a half-chair conformation. The five-membered thia-zole ring adopts a
      slightly twisted envelope conformation and the pyrrole ring adopts an envelope
      conformation; in each case, the C atom linking the rings is the flap atom. The
      mol-ecular structure features inter- and intra-molecular C-H?O inter-actions.
      Furthermore, the crystal packing is stabilized by four inter-molecular C-H?pi
      inter-actions.

PMID- 22412716
TI  - N-(7-Bromo-9-butyl-9H-carbazol-2-yl)-9,9-diethyl-N,N,N-triphenyl-9H-fluorene-2,7
      diamine.
AB  - In the title mol-ecule, C(51)H(46)BrN(3), the central fluorene residue is planar
      (r.m.s. deviation = 0.0203 A), as is the carbazole system (r.m.s. deviation =
      0.0154 A), and these groups are almost orthogonal [dihedral angle = 79.72 (3)
      degrees ]. The three-dimensional architecture is consolidated by C-H?pi inter
      actions. The butyl substituent is disordered with two sites resolved for the
      terminal propyl atoms; the major component had a site-occupancy factor of 0.686
      (3).

PMID- 22412717
TI  - 6-Methyl-3-phenyl-2-sulfanyl-idene-1,2,3,4-tetra-hydro-quinazolin-4-one.
AB  - The title compound, C(15)H(12)N(2)OS, exists as the thione tautomer in the solid
      state. The phenyl group is almost perpendicular [dihedral angle = 87.96 (5)
      degrees ] to the fused ring system (r.m.s. deviation = 0.036 A for 13 ring and
      exocyclic non-H atoms). In the crystal, centrosymmetric dimers, sustained by
      pairs of N-H?S hydrogen bonds, are connected into layers parallel to (-101) by C
      H?O and C-H?S inter-actions.

PMID- 22412718
TI  - 2-Methyl-3-(2-methyl-phen-yl)-7-nitro-quinazolin-4(3H)-one.
AB  - In the title methaqua-lone analogue, C(16)H(13)N(3)O(3), the 2-tolyl group is
      almost orthogonal [dihedral angle = 85.20 (5) degrees ] to the fused ring system
      (r.m.s. deviation of fitted non-H atoms = 0.029 A). In the crystal, twofold
      symmetry generates two-mol-ecule aggregates linked by C-H?O and pi-pi inter
      actions [ring centroid-centroid distance = 3.4967 (6) A].

PMID- 22412719
TI  - 8-Benz-yloxy-2-methyl-3-(2-methyl-phenyl)quinazolin-4(3H)-one.
AB  - In the title methaqua-lone analogue, C(23)H(20)N(2)O(2), the planes of the
      terminal aromatic rings [dihedral angle between them = 64.52 (7) degrees ]
      approximately face the fused-ring methyl group and both are twisted with respect
      to the pyrimidine plane (r.m.s. deviation = 0.028 A), forming dihedral angles of
      86.9 (3) (with the 2-tolyl ring) and 65.57 (7) degrees . The 2-tolyl residue is
      disordered over two almost coplanar but opposite orientations with the major
      component having a site-occupancy factor of 0.893 (3). The three-dimensional
      crystal packing is consolidated by C-H?O, C-H?pi and pi-pi [2-tol-yl-2-tolyl
      centroid-centroid distance = 3.8099 (6) A] inter-actions.

PMID- 22412720
TI  - exo,exo-4-(2-Hy-droxy-eth-yl)-10-oxa-4-aza-tricyclo-[5.2.1.0]dec-8-ene-3,5-dione.
AB  - In the crystal of the title compound, C(10)H(11)NO(4), the hy-droxy group forms
      an O-H?O(carbon-yl) hydrogen bond with an adjacent molecule, so forming chains
      which extend along (010). Further weak C-H?O hydrogen-bonding associations give
      an infinite three-dimensional network structure.

PMID- 22412721
TI  - 3-{[(4Z)-1,2-Dimethyl-5-oxoimidazol-4-yl-idene]meth-yl}-4-hy-droxy-benzonitrile.
AB  - In the title compound, C(13)H(11)N(3)O(2), an intra-molecular O-H?N hydrogen bond
      generates an S(7) ring. The dihedral angle between the mean plane of the benzene
      ring and the imidazolidinone ring is 3.05 (2) degrees . In the crystal, inversion
      related mol-ecules are linked by dual C-H?O(carbon-yl) hydrogen bonds to form a
      dimer with an R(2) (2)(14) graph-set motif. A C-H?O(hy-droxy) inter-action links
      pairs of mol-ecules into another type of cyclic dimer with an R(2) (2)(18) motif.
      The mol-ecules are further linked by C-H?N inter-actions to form layers parallel
      to (001). Offset pi-pi stacking [3.3877 (8) A] is observed in the crystal
      structure, with an inter-planar spacing between the planes of neighboring benzene
      rings of 3.444 (1) A.

PMID- 22412722
TI  - 4,9,12,15-Tetra-oxa-3,5,8,10,14,16-hexa-aza-tetra-cyclo-[11.3.0.0.0]hexa-deca
      1(16),2,5,7,10,13-hexaen-3-ium-3-olate monohydrate.
AB  - The organic mol-ecule in the title monohydrate, C(6)N(6)O(5).H(2)O, presents an
      almost planar configuration, the greatest deviation from the least-squares plane
      through the atoms being 0.061 (1) A for the O atom within the seven-membered
      ring. Each water H atom is bifurcated, one forming two O-H?N hydrogen bonds and
      the other forming O-H?N,O hydrogen bonds. The result of the hydrogen bonding is
      the formation of supra-molecular layers with a zigzag topology that stack along
      [001].

PMID- 22412723
TI  - 1-Formyl-c-3,t-3-dimethyl-r-2,c-6-di-phenyl-piperidin-4-one.
AB  - In the title compound, C(20)H(21)NO(2), the piperidine ring adopts a distorted
      boat conformation. The phenyl rings substituted at the 2- and 6-positions of the
      piperidine ring subtend angles of 86.0 (1) and 67.3 (1) degrees  with the mean
      plane of the piperidine ring (all six non-H atoms). The crystal packing features
      C-H?O inter-actions.

PMID- 22412724
TI  - 5-(2-Nitro-1-phenyl-but-yl)-4-phenyl-1,2,3-selenadiazole.
AB  - In the title compound, C(18)H(17)N(3)O(2)Se, the selenadiazole ring is planar
      [maximum deviation = 0.012 (2) A for the ring C atom bearing the phenyl
      substituent]. The dihedral angle between the selenadiazole ring and the attached
      benzene ring is 46.5 (1) degrees . There is one short intra-molecular C-H?Se
      contact.

PMID- 22412725
TI  - 2-Methylxanthen-9-one.
AB  - In the title compound, C(14)H(10)O(2), the tricycle is not planar, being bent
      with a dihedral angle of 4.7 (1) degrees  between the two benzene rings. In the
      crystal, pi-pi inter-actions between the six-membered rings of neighbouring mol
      ecules [centroid-centroid distances = 3.580 (3) and 3.605 (3) A] form stacks
      propagating along [101].

PMID- 22412726
TI  - N-(4-Chloro-3-nitro-phen-yl)maleamic acid.
AB  - In the mol-ecule of the title compound, C(10)H(7)ClN(2)O(5), the acyclic C=C
      double bond is cis configured. The C=O and O-H bonds of the acid group are in a
      relatively rare anti position to each other, due to the donation of
      intramolecular hydrogen bond to the amide by the carboxyl group. The nitro group
      is significantly twisted [dihedral angle = 66.9 (3) degrees ] out of the plane of
      the remaining atoms, which are almost coplanar (r.m.s. deviation for non-H atoms
      except the nitro group = 0.202 A). In the crystal, N-H?O hydrogen bonds link the
      mol-ecules into zigzag chains running along the b axis.

PMID- 22412727
TI  - Methyl 2,2-diphenyl-2-(prop-2-yn-1-yl-oxy)acetate.
AB  - The mol-ecular structure of the title compound, C(18)H(16)O(3), exhibits a new
      R(2)-C(COOMe)(OCH(2)CCH) group. The C-O-C-C torsion angle is 153.3 (1) degrees .
      The dihedral angles are 79.89 (5) degrees  between phen-yl/phenyl planes, and
      73.13 (5) and 79.05 (8) degrees  for the two COOMe/phenyl plane pairs.

PMID- 22412728
TI  - 4-(4-Meth-oxy-phen-yl)naphtho-[2,3-b]thio-phene.
AB  - In the title compound, C(19)H(14)OS, the naphtho-thio-phene moiety is almost
      planar except for the S atom of the five-membered ring, which is situated 0.047
      (6) A out of the C(4) plane (with an r.m.s. deviation of fitted atoms = 0.0009
      A). The dihedral angle between the naphtho-thio-phene plane and the attached meth
      oxy-phenyl ring is 67.6 (2) degrees . In the crystal, a C-H?pi inter-action is
      observed between a meth-oxy-phenyl C-H group and the outer benzene ring of the
      naphtho-thio-phene moiety. The five-membered ring of the naphtho-thio-phene
      moiety is disordered, with the S and opposite non-fused C atom approximately
      exchanging positions, with a site-occupancy factors of 0.808 (3) and 0.187 (3).

PMID- 22412729
TI  - Ethyl 1-(4-chloro-benz-yl)-3-phenyl-1H-pyrazole-5-carboxyl-ate.
AB  - In the title compound, C(19)H(17)ClN(2)O(2), the pyrazole ring makes dihedral
      angles of 6.97 (5) and 79.25 (1) degrees , respectively, with the phenyl and
      chlorophenyl rings, respectively. In the crystal, C-H?O hydrogen bonds are
      observed.

PMID- 22412730
TI  - (7-Chloro-2-oxo-2H-chromen-4-yl)methyl piperidine-1-carbodithio-ate.
AB  - In the title compound, C(16)H(16)ClNO(2)S(2), the piperidine ring is in a chair
      conformation. In the coumarin ring system, the dihedral angle between the benzene
      and pyran rings is 3.5 (1) degrees . In the crystal, a weak C-H?O hydrogen bond
      links mol-ecules into chains along [001]. In addition, pi-pi stacking inter
      actions are present involving the benzene and pyran rings, with a centroid-to
      centroid distance of 3.712 (2) A. The crystal studied is a nonmerohedral twin
      with refined components 0.221 (1) and 0.779 (1).

PMID- 22412731
TI  - Ethyl 6-(4-fluoro-phen-yl)-4-hy-droxy-2-sulfanyl-idene-4-trifluoro-methyl-1,3
      diazinane-5-carboxyl-ate.
AB  - In the title compound, C(14)H(14)F(4)N(2)O(3)S, the hexa-hydro-pyrimidine ring
      adopts a half-chair conformation. The mol-ecular conformation is stabilized by an
      intra-molecular O-H?O hydrogen bond, generating an S(6) ring. The crystal
      structure features O-H?S and N-H?S hydrogen bonds.

PMID- 22412732
TI  - (1R*,2S*)-2-Nitro-1-(4-nitro-phen-yl)propanol.
AB  - The title compound, C(9)H(10)N(2)O(5), presents a racemic mixture of two enanti
      omeric diastereomers. In the crystal, mol-ecules assemble into zigzag chains
      parallel to the b axis [C(6) motif] due to the formation of elongated O-H?O(N)
      hydrogen bonds. Of inter-est is the fact that only the aliphatic nitro group is
      involved in hydrogen bonding and it adopts a gauche conformation with respect to
      the OH group.

PMID- 22412733
TI  - N-[2-(3,4-Dimeth-oxy-phen-yl)eth-yl]-N-methyl-benzene-sulfonamide.
AB  - In the title compound, C(17)H(21)NO(4)S, the phenyl and dimeth-oxy-phenyl rings
      are almost perpendicular to each other, making a dihedral angle of 82.57 (5)
      degrees . The structure is stabilized by inter-molecular C-H?O inter-actions and
      the packing is further enhanced by C-H ?pi inter-actions.

PMID- 22412734
TI  - (S)-Benzyl 3-phenyl-carbamoyl-1,2,3,4-tetra-hydro-isoquinoline-2-carboxyl-ate.
AB  - There are two independent mol-ecules in the asymmetric unit of the title
      compound, C(24)H(22)N(2)O(3). The heterocyclic ring assumes a twisted boat
      conformation and N-H?O inter-actions help to construct the three-dimensional
      network within the crystal packing.

PMID- 22412735
TI  - 1-[(2-Hy-droxy-phen-yl)(pyrrolidin-1-yl)-meth-yl]naphthalen-2-ol N,N-dimethyl
      formamide monosolvate.
AB  - The title compound, C(21)H(21)NO(2).C(3)H(7)NO, was synthesized by solvent-free
      one-pot three-component reaction of naphthalen-2-ol, 2-hy-droxy-benzaldehyde and
      pyrrolidine. The dihedral angle between the naphthalene ring system and the
      benzene ring is 77.74 (6) degrees . The pyrrolidine ring assumes an envelope
      conformation. An intra-molecular O-H?N and an inter-molecular O-H?O hydrogen bond
      are observed.

PMID- 22412736
TI  - 2-(Morpholin-4-yl)-6-(1H-pyrrol-1-yl)-pyridine-3,5-dicarbonitrile.
AB  - In the title compound, C(15)H(13)N(5)O, the morpholine ring adopts a chair
      conformation. The dihedral angle between the pyrrole ring and the pyridine ring
      is 28.93 (14) degrees . In the crystal, the molecules are linked by C-H?O
      hydrogen bonds occur, and aromatic weak pi-pi stacking [centroid-centroid
      separation = 4.178 (2) A] and C-H?pi inter-actions consolidate the packing.

PMID- 22412737
TI  - (E)-1-(3-Bromo-phen-yl)-3-(3,4-dimeth-oxy-phen-yl)prop-2-en-1-one.
AB  - The mol-ecular structure of the title compound, C(17)H(15)BrO(3), consists of a
      bromo-phenyl and a 3,4-dimeth-oxy-phenyl group linked through a prop-2-en-1-one
      spacer. The C=C double bond displays an E conformation, while the carbonyl group
      shows an S-cis conformation relative to the double bond.

PMID- 22412738
TI  - N-(4-Methyl-benzo-yl)-4-nitro-benzene-sulfonamide.
AB  - In the title compound, C(14)H(12)N(2)O(5)S, the dihedral angle between the nitro
      phenyl group and the -S-NH-C-O fragment is 80.74 (17) degrees  and that between
      the nitro-phenyl and methyl-phenyl groups is 87.66 (14) degrees . The C-S-N-C
      torsion angle at the S-N bond is -67.0 (3) degrees . In the crystal, mol-ecules
      are linked into C(4) chains via N-H?O hydrogen bonds.

PMID- 22412739
TI  - N-(3-Chloro-4-methyl-phen-yl)maleamic acid.
AB  - In the title compound, C(11)H(10)ClNO(3), the dihedral angle between the benzene
      ring and the amide group is 6.6 (10) degrees  and an intramolecular O-H?O
      hydrogen bond occurs. In the crystal, molecules are linked by N-H?O hydrogen
      bonds, generating C(7) zigzag chains.

PMID- 22412740
TI  - N-[2-(3,4-Dimeth-oxy-phenyl)eth-yl]-N-methyl-naphthalene-1-sulfonamide.
AB  - In the title compound, C(21)H(23)NO(4)S, the dihedral angle between the
      naphthalene residue and the benzene ring is 7.66 (3) degrees . In the molecule,
      there are some short C-H?O interactions. In the crystal, the structure is
      stabilized by weak intra-molecular C-H?O hydrogen bonds and the crystal structure
      is stabilized by weak C-H?O, C-H?pi and pi-pi [centroid-centroid distance = 3.710
      (2) A] inter-actions.

PMID- 22412741
TI  - Ethyl 4-methyl-1,3-dioxo-1,2,3,4-tetra-hydro-isoquinoline-4-carboxyl-ate.
AB  - In the title compound, C(13)H(13)NO(4), the fused-ring system is nearly planar,
      with an r.m.s. deviation of 0.0408 A. In the crystal, mol-ecules are linked into
      centrosymmetric dimers by a pair of N-H?O hydrogen bonds. The ethyl group is
      disordered over two positions in a ratio of 0.758 (6):0.242 (6).

PMID- 22412742
TI  - Diethyl 2,6-dimethyl-4-(5-phenyl-1H-pyrazol-4-yl)-1,4-dihydro-pyridine-3,5
      dicarboxyl-ate.
AB  - In the title compound, C(22)H(25)N(3)O(4), the dihydro-pyridine ring adopts a
      flattened boat conformation. The pyrazole ring makes a dihedral angle of 29.04
      (5) degrees  with the benzene ring. The mol-ecular structure is stabilized by an
      intra-molecular C-H?O hydrogen bond which generates an S(9) ring motif. In the
      crystal, mol-ecules are linked via N-H?O and C-H?N hydrogen bonds into a two
      dimensional network parallel to the ab plane. The crystal structure is further
      consolidated by weak C-H?pi inter-actions.

PMID- 22412743
TI  - Diisopropyl-ammonium thio-cyanate.
AB  - In the title mol-ecular salt, C(6)H(16)N(+).NCS(-), the cation possesses
      approximate local twofold rotation symmetry. One of its NH atoms forms a hydrogen
      bond to a thio-cyanate N atom and the other to a thio-cyanate S atom. This
      results in [001] chains of alternating cations and anions.

PMID- 22412744
TI  - N-[3-(Dimethyl-amino)-prop-yl]-N'-(2-hy-droxy-5-methyl-phen-yl)oxamide.
AB  - In the title compound, C(14)H(21)N(3)O(3), the oxamide group has a transoid
      conformation. In the crystal, the mol-ecules are connected by N-H?O and O-H?N
      hydrogen bonds into a double chain running along the b axis.

PMID- 22412745
TI  - 2-[(3R,6R)-6-Methyl-2,5-dioxomorph-olin-3-yl]-N-(propan-2-yl)acetamide.
AB  - The molecular conformation of the title compound, C(10)H(16)N(2)O(4), is
      determined by an intra-molecular N-H?O hydrogen bond involving the morpholine NH
      group and the amide O atom. In the crystal, mol-ecules are linked by N-H?O
      hydrogen bonds into chains along the a-axis direction.

PMID- 22412746
TI  - 4-[(E)-(4-Methyl-phen-yl)imino-meth-yl]phenol.
AB  - In the title compound, C(14)H(13)NO, the two rings show significant deviation
      from coplanarity, with a dihedral angle between the two planes of 49.40 (5)
      degrees . The hy-droxy group is involved in an inter-molecular O-H?N hydrogen
      bond, forming an extended one-dimensional zigzag chain along (001).

PMID- 22412747
TI  - 1-Methyl-2-[(E)-2,4,5-trimeth-oxy-styr-yl]-pyridinium benzene-sulfonate mono
      hydrate.
AB  - The asymmetric unit of the title compound, C(17)H(20)NO(3) (+).C(6)H(5)O(3)S(
      ).H(2)O, comprises two 1-methyl-2-[(E)-2,4,5-trimeth-oxy-styr-yl]pyridinium
      cations, two benzene-sulfonate anions and two water mol-ecules. The cations exist
      in the E conformation with respect to the C=C bond; one cation is essentially
      planar while the other is slightly twisted, the dihedral angles between the
      pyridinium and phenyl rings being 1.23 (14) and 6.64 (13) degrees , respectively.
      In the crystal, cations, anions and water mol-ecules are linked by O-H?O hydrogen
      bonds and weak C-H?O inter-actions into chains along the b axis. pi-pi inter
      actions with centroid-centroid distances in the range 3.5557 (16)-3.6876 (16) A
      are observed. C-H?pi inter-actions and a C?O short contact [2.94 (4) A] are also
      observed.

PMID- 22412748
TI  - 1d-1-O-tert-Butyl-diphenyl-silyl-2,3,6-O-tris-(meth-oxy-methyl-ene)-myo-inositol
      4,5-bis-(dibenzyl-phosphate).
AB  - THE TITLE COMPOUND [SYSTEMATIC NAME: tetra-benzyl (1R,2R,3S,4R,5R,6S)-4-(tert
      butyl-diphenyl-sil-yloxy)-3,5,6-tris-(meth-oxy-meth-oxy)cyclo-hexane-1,2-diyl bis
      phosphate], C(56)H(68)O(15)P(2)Si, was isolated as an inter-mediate in the
      preparation of a phosphatidylinositol phosphate for biological studies. In the
      crystal, the mol-ecules are connected via one methyl-ene C-H?pi and two weak phen
      yl-ether C-H?O inter-actions. One benz-yloxy group is disordered over two
      overlapping positions with an occupancy ratio of 0.649 (7):0.351 (7).

PMID- 22412749
TI  - N-(2-Hy-droxy-eth-yl)-5-(4-meth-oxy-phen-yl)-4H-pyrazole-3-carboxamide.
AB  - In the title compound, C(13)H(15)N(3)O(3), the dihedral angle between the benzene
      and pyrazole rings is 7.7 (1) degrees  and the O-C-C-N torsion angle of the side
      chain is 74.1 (2) degrees . In the crystal, mol-ecules are linked by O-H?O, N-H?O
      and N-H?N hydrogen bonds.

PMID- 22412750
TI  - (Z)-4-(2-Hy-droxy-benzyl-idene)-1-methyl-2-phenyl-1H-imidazol-5(4H)-one.
AB  - In the title compound, C(17)H(14)N(2)O(2), the asymmetric unit comprises two mol
      ecules that are comformationally similar [the dihedral angles between the phenyl
      rings in each are 46.35 (2) and 48.04 (3) degrees ], with the conformation
      stabilized by intra-molecular O-H?N hydrogen bonds, which generate S(7) rings. In
      the crystal, inversion-related mol-ecules are linked by pairs of weak C-H?O
      hydrogen bonds, forming dimers with an R(2) (2)(16) graph-set motif. Weak inter
      ring pi-pi stacking is observed in the structure, the shortest centroid-to
      centroid distance being 3.7480 (13) A.

PMID- 22412751
TI  - (E)-4-[(4-Diethyl-amino-2-hy-droxy-benzyl-idene)amino]-benzonitrile.
AB  - The title compound, C(18)H(19)N(3)O, displays an E conformation with respect to
      the C=N double bond. The dihedral angle between the mean planes of the two
      benzene rings is 24.49 (3) degrees . An intra-molecular O-H?N hydrogen bond
      generates an S(6) ring. In the crystal, mol-ecules are linked by nonclassical
      inter-molecular C-H?O hydrogen bonds to form an infinite one-dimensional chain
      along [010], generating a C(8) motif.

PMID- 22412752
TI  - [8-(4-Chloro-benzo-yl)-2,7-dimeth-oxy-naphthalen-1-yl](2,4,6-trimethyl-phen
      yl)methanone.
AB  - In the title compound, C(29)H(25)ClO(4), the dihedral angle between the benzene
      rings of the 2,4,6-trimethyl-benzoyl group and the 4-chloro-benzoyl group is
      65.19 (9) degrees . The dihedral angles between the naphthalene ring system and
      the benzene rings of the 2,4,6-trimethyl-benzoyl group and the 4-chloro-benzoyl
      group are 85.66 (8) and 69.48 (8) degrees , respectively. In the crystal, two
      types of inter-molecular C-H?O inter-actions and an intra-molecular C-H?O inter
      action are observed. Moreover, there is a short intra-molecular C=O?C=O contact
      of 2.614 (2) A between the benzoyl substituents.

PMID- 22412753
TI  - 2,6-Bis[(S)-1-phenyl-eth-yl]-1H,5H-pyrrolo-[3,4-f]isoindole-1,3,5,7(2H,6H)
      tetrone.
AB  - In the title compound, C(26)H(20)N(2)O(4), the central isoindole core is almost
      planar (r.m.s. deviation = 0.043 A). The phenyl rings lie to either side of the
      plane [dihedral angles = 88.64 (5) and 67.74 (6) degrees ] and the dihedral angle
      between the phenyl rings is 63.39 (7) degrees . In the crystal, mol-ecules are
      linked by C-H?O inter-actions; notably, one carbonyl O atom accepts three such
      bonds.

PMID- 22412754
TI  - 1-Acetyl-4-(phenyl-sulfan-yl)imidazolidin-2-one.
AB  - The five-membered ring in the title imidazolidinone derivative,
      C(11)H(12)N(2)O(2)S, adopts an envelope conformation with the S-bound C atom
      being the flap atom. Overall, the mol-ecule has a U-shaped conformation as both
      rings are folded towards each other [dihedral angle = 31.66 (6) degrees ]. An
      eight-membered amide {?HNCO}(2) synthon leads to hydrogen-bonded dimeric
      aggregates in the crystal: these are additionally linked by C-H?pi inter-actions.

PMID- 22412755
TI  - 1,3-Bis{[(4-methyl-phen-yl)sulfon-yl]-oxy}propan-2-yl 4-methyl-benzene-sulfonate.
AB  - In the title sulfonate derivative, C(24)H(26)O(9)S(3), all atoms apart from those
      of one of the 4-methyl-benzene-sulfonate residues lie approximately in a disc;
      the dihedral angles between the approximately orthogonal benzene ring and those
      in the plane are 74.53 (9) and 67.79 (11) degrees . In the crystal, mol-ecules
      are consolidated into the three-dimensional architecture by C-H?O inter-actions.
      One of the 4-methyl-benzene-sulfonate residues is disordered over two almost
      parallel positions; the major component refined to a site-occupancy factor of
      0.918 (2).

PMID- 22412756
TI  - N-(9,9-Dipropyl-9H-fluoren-2-yl)-7-(piperidin-1-yl)-2,1,3-benzothia-diazol-4
      amine.
AB  - In the title compound, C(30)H(34)N(4)S, each of the benzothia-diazole and
      fluorene fused ring systems is almost planar (r.m.s. deviations = 0.010 and 0.013
      A, respectively) and they are inclined to each other with a dihedral angle of
      61.69 (3) degrees ; the S atom is directed away from the rest of the mol-ecule.
      Each of the benzothiadiazole ring N atoms forms a significant intra-molecular
      contact, i.e. N-H?N or C-H?N. In the crystal, linear supra-molecular chains along
      the c axis are generated by C-H?N inter-actions involving the tertiary amine N
      atom.

PMID- 22412757
TI  - 2-(4-Carb-oxy-piperidinium-1-yl)pyridine-3-carboxyl-ate.
AB  - The title compound, C(12)H(14)N(2)O(4), crystallizes as a zwitterion. A negative
      charge is delocalized in the deprotonated carboxyl group attached to the pyridine
      ring. The piperidine N atom accepts a proton and the ring is transformed into a
      piperidinium cation. There is an intra-molecular N-H?O hydrogen bond between the
      protonated NH and a carboxyl-ate O atom. In the crystal, an O-H?O hydrogen bond
      between the carboxyl group and the carboxyl-ate O atom of another mol-ecule
      generates a helix along the b axis.

PMID- 22412758
TI  - 2-(Ammonio-meth-yl)pyridinium sulfate monohydrate.
AB  - In the crystal of the title hydrated molecular salt, C(6)H(10)N(2) (2+).SO(4) (2
      ).H(2)O, N-H?O and O-H?O hydrogen bonds link the mol-ecules into layers parallel
      to the ab plane. C-H?O hydrogen bonds are observed both within these layers and
      between mol-ecules and ions in adjacent layers.

PMID- 22412760
TI  - Ethyl N-(2-benzoyl-4-chloro-phen-yl)-ethane-carboximidate.
AB  - In the title compound, C(17)H(16)ClNO(2), the N=C-O-C-C fragment is planar within
      0.029 (1) A, and makes dihedral angles of 66.71 (8) and 59.61 (8) degrees  with
      the planes of the chloro-phenyl and benzoyl rings, respectively. The carbonyl C=O
      bond is not coplanar with either of the aromatic rings; it makes angles of 42.5
      and 23.5 degrees  with the normals to the ring planes. In the crystal, very weak
      C-H?O, C-H?Cl, C-H?pi and pi-pi [inter-planar distance = 3.53 (1) A] inter
      actions are observed.

PMID- 22412759
TI  - 1'-Methyl-4'-phenyl-dispiro-[chromane-3,3'-pyrrolidine-2',3''-indoline]-2,2''
      dione.
AB  - In the title compound, C(26)H(22)N(2)O(3), the pyrrolidine ring adopts an
      envelope conformation with the N atom as the flap. In the crystal, pairs of
      centrosymmetrically related mol-ecules are linked into dimers by N-H?O hydrogen
      bonds. In addition, there are C-H?O hydrogen bonds.

PMID- 22412761
TI  - Ethyl 5-amino-3-(pyridin-4-yl)-1-(2,4,6-tri-chloro-phen-yl)-1H-pyrazole-4-carb
      oxyl-ate dimethyl sulfoxide hemisolvate.
AB  - The asymmetric unit of the title compound, C(17)H(13)Cl(3)N(4)O(2).0.5C(2)H(6)OS,
      contains two almost identical mol-ecules and one dimethyl sulfoxide (DMSO-d(6))
      solvent mol-ecule. The pyrazole ring forms dihedral angles of 54.6 (4) and 80.0
      (4) degrees  in one mol-ecule, and dihedral angles of 54.2 (4) and 81.2 (4)
      degrees  in the other mol-ecule, with the directly attached pyridine and
      trichloro-phenyl rings, respectively. The dihedral angles of the pyridine and
      trichloro-phenyl rings are 51.2 (4) and 52.0 (4) degrees , respectively. The
      crystal packing is characterized by intra- and inter-molecular hydrogen bonds.
      The crystal is a nonmerohedral twin with a contribution of 0.488 (1) for the
      minor twin component. The terminal ethyl group of one mol-ecule and the S atom of
      DMSO are disordered over two sites.

PMID- 22412762
TI  - 4-(1-Cyclo-propyl-6-fluoro-4-oxo-1,4-dihydro-quinolin-7-yl)piperazin-1-ium 2,4,5
      tricarb-oxy-benzene-1-carboxyl-ate monohydrate.
AB  - In the crystal of title compound, C(16)H(19)FN(3)O(+).C(10)H(5)O(8) (-).H(2)O,
      the water mol-ecule and the ions are connected by inter-molecular N-H?O and O-H?O
      hydrogen bonds and pi-pi stacking [centroid-centroid separation = 3.602 (1) A]
      between the benzene ring and the pyridine ring, generating a three-dimensional
      supra-molecular structure.

PMID- 22412763
TI  - l-Tryptophan 4-nitro-phenol tris-olvate.
AB  - The title compound, C(11)H(12)N(2)O(2).3C(6)H(5)NO(3), comprises a zwitterionic
      amino acid formed by two nearly planar groups: (i) the indole ring and Cbeta, and
      (ii) the carboxyl group, Calpha, as well as the amine N atom, with r.m.s.
      deviations of 0.0084 and 0.0038 A, respectively. The angle between these
      idealized planes is 39.47 (9) degrees . The amine group of the amino acid is in a
      syn (-sc) arrangement relative to the ring system. The overall crystal structure
      results from the packing of sheets parallel to the (001) planes. These sheets are
      formed by a pair of screw axis related parallel networks bound by hydrogen-bond
      and pi-pi stacking interactions. The intermolecular cohesion of all organic
      residues in each of the latter two-dimensional networks is achieved via strong
      hydrogen bonding, nitro-pi and pi-pi stacking interactions.

PMID- 22412764
TI  - Bis(2,6-dichloro-benz-yl)selane.
AB  - The title mol-ecule, C(14)H(10)Cl(4)Se, features a selenide bridge between two
      dichloro-benzyl units. The dihedral angle between the two benzene rings is 107.9
      (16) degrees . In the crystal, weak pi-pi face-to-face aromatic inter-actions are
      observed [centroid-centroid distance between two adjacent (but
      crystallographically different) phenyl rings = 3.885 (5) A], providing some
      packing stability. Short Cl?Cl contacts of 3.41 (2) A are observed.

PMID- 22412765
TI  - Premedication: Is clonidine the answer?

PMID- 22412768
TI  - Retraction note.

PMID- 22412767
TI  - Thermoregulation and neuroanesthesia.

PMID- 22412769
TI  - A comparison of midazolam and clonidine as an oral premedication in pediatric
      patients.
AB  - BACKGROUND: To compare oral midazolam (0.5 mg/kg) versus oral clonidine (4
      MUg/kg) as a premedication in pediatric patients aged between 2-12 years with
      regard to sedation and anxiolysis. METHODS: Sixty pediatric patients belonging to
      the American Society of Anesthesiologists class I and II between the age group of
      2-12 years scheduled for elective surgery were randomly allocated to receive
      either oral midazolam (group I) 30 min before induction or oral clonidine (group
      II) 90 min before induction of anesthesia. The children were evaluated for levels
      of sedation and anxiety at the time of separation from the parents, venepuncture,
      and at the time of mask application for induction of anesthesia. RESULTS: After
      premedication, the percentage of children who were sedated and calm increased in
      both the groups. The overall level of sedation was better in the children in the
      clonidine group, but children in the midazolam group had a greater degree of
      anxiolysis at times of venepuncture and mask application. In addition, midazolam
      did not cause significant changes in hemodynamics unlike clonidine where a
      significant fall in blood pressure was noted, after premedication, but
      preinduction. CONCLUSION: We conclude that under the conditions of the study,
      oral midazolam is superior to clonidine as an anxiolytic in pediatric population.
      Clonidine with its sedative action especially at the time of separation from
      parents along with its other perioperative benefits cannot be discounted.

PMID- 22412770
TI  - Comparison of propofol versus sevoflurane on thermoregulation in patients
      undergoing transsphenoidal pituitary surgery: A preliminary study.
AB  - PURPOSE: General anesthesia causes inhibition of thermoregulatory mechanisms.
      Propofol has been reported to cause more temperature fall, but in case of
      deliberate mild hypothermia, both sevoflurane and propofol were comparable.
      Thermoregulation is found to be disturbed in cases of pituitary tumors. We aimed
      to investigate which of the two agents, sevoflurane or propofol, results in
      better preservation of thermoregulation in patients undergoing transsphenoidal
      excision of pituitary tumors. METHODS: Twenty-six patients scheduled to undergo
      transsphenoidal removal of pituitary adenomas were randomly allocated to receive
      propofol or sevoflurane anesthesia. Baseline esophageal temperature was noted.
      Times for temperature to fall by 1 degrees C or 35 degrees C and to return to
      baseline were also comparable (P>0.05). After that warmer was started at 43
      degrees C and time to rise to baseline was noted. Duration of surgery, total
      blood loss, and total fluid intake were also noted. If any, side effects such as
      delayed arousal and recovery from muscle relaxant were noted. RESULTS: The
      demographics of the patients were comparable. Duration of surgery and total blood
      loss were comparable in the two groups. The time for temperature to fall by 1
      degrees C or 35 degrees C and time to return to baseline was also comparable
      (P>0.05). No side effects related to body temperature were noted. CONCLUSION:
      Both propofol and sevoflurane show similar effects in maintaining thermal
      homeostasis in patients undergoing transsphenoidal pituitary surgery.

PMID- 22412771
TI  - The outcome of thoracic epidural anesthesia in elderly patients undergoing
      coronary artery bypass graft surgery.
AB  - BACKGROUND: Thoracic epidural anesthesia (TEA) improves analgesia and outcomes
      after a cardiac surgery. As aging is a risk factor for postoperative pulmonary
      complications, TEA is of particular importance in elderly patients undergoing
      coronary artery bypass graft (CABG). METHODS: Fifty patients aged 65-75 years;
      ASA II and III scheduled for elective CABG were included in the study. Patients
      were randomized to receive either general anesthesia (GA) group alone or GA
      combined with TEA group. Heart rate (HR), mean arterial pressure (MAP), and
      central venous pressure were recorded. Total dose of fentanyl MUg/kg, aortic
      cross clamping, cardiopulmonary bypass (CPB) time, time to first awaking and
      extubation, arterial blood gases, visual analog scale (VAS) score in intensive
      care unit were reported. Postoperative pulmonary function tests were done.
      RESULTS: TEA showed a significant HR and lower MAP compared with the GA group.
      The total dose of intraoperative fentanyl and nitroglycerine were significantly
      lower in the TEA. Patients in TEA group have statistically significantly higher
      PaO(2), lower PaCO(2), increase in Forced Vital Capacity (FVC) and Forced
      Expiratory Volume in one second (FEV(1)) CONCLUSIONS: TEA reduced severity of
      postoperative pulmonary function and restoration was faster in TEA group in
      elderly patients undergoing CABG. Also, it resulted in earlier extubation and
      awakening, better analgesia, lower VAS.

PMID- 22412772
TI  - The efficacy of 0.75% levobupivacaine versus 0.75% ropivacaine for peribulbar
      anesthesia in vitreoretinal surgery.
AB  - BACKGROUND: We evaluated the anesthetic efficacy and the postoperative analgesic
      effects of 0.75% levobupivacaine versus 0.75% ropivacaine for peribulbar
      anesthesia in patients undergoing primary vitreoretinal surgery. METHODS: We
      investigated 120 patients subjected to vitreoretinal surgery under peribulbar
      anesthesia. They were randomized into two equal groups according to the local
      anesthetic (LA) used, namely, 0.75% levobupivacaine or 0.75% ropivacaine, both
      with the addition of hyaluronidase. Nerve block was carried out by injection of 5
      7 mL of the LA using single injection percutaneous peribulbar anesthesia with a
      short needle. RESULTS: When compared with 0.75% ropivacaine, 0.75%
      levobupivacaine provided more successful akinesia at 10 min after block
      (P=0.026), fewer supplementary injections (P=0.026), and less volume (mL) was
      used (P=0.031). Also, levobupivacaine provided significantly longer motor block
      duration (342+/-27 min versus 206+/-40 min, P=0.001) and significantly longer
      sensory block duration (513+/-24 min versus 394+/-11 min, P=0.001) when compared
      with ropivacaine. In the postoperative period, the patients in the
      levobupivacaine group achieved lower values of verbal numeric rating scale of
      pain compared with patients in the ropivacaine group among the period from 4 to
      12 h. Also, there were significantly (P=0.001) lower diclofenac consumption (mg)
      and the percentage of patients who required tramadol rescue medication were
      significantly less (P=0.034) in the levobupivacaine group compared with the
      ropivacaine group. CONCLUSION: We are concluding that, at equipotent doses and
      concentrations, 0.75% levobupivacaine provides more effective peribulbar
      anesthesia and more effective postoperative analgesia for vitreoretinal surgery
      compared with 0.75% ropivacaine.

PMID- 22412773
TI  - Combined spinal epidural anesthesia for laparoscopic appendectomy in adults: A
      case series.
AB  - BACKGROUND: Laparoscopy is one of the most common surgical procedures and is the
      procedure of choice for most of the elective abdominal surgeries performed
      preferably under endotracheal general anesthesia. Technical advances in the field
      of laparoscopy have helped to reduce surgical trauma and discomfort, reduce
      anesthetic requirement resulting in shortened hospital stay. Recently, regional
      anaesthetic techniques have been found beneficial, especially in patients at a
      high risk to receive general anesthesia. Herewith we present a case series of
      laparoscopic appendectomy in eight American Society of Anaesthesiologists (ASA) I
      and II patients performed under spinal-epidural anaesthesia. METHODS: Eight ASA
      Grade I and II adult patients undergoing elective Laparoscopic appendectomy
      received Combined Spinal Epidural Anaesthesia. Spinal Anaesthesia was performed
      at L(2)-L(3) interspace using 2 ml of 0.5% (10 mg) hyperbaric Bupivacaine mixed
      with 0.5ml (25 micrograms) of Fentanyl. Epidural catheter was inserted at T(10)
      T(11) interspace for inadequate spinal anaesthesia and postoperative pain relief.
      Perioperative events and operative difficulty were studied. Systemic drugs were
      administered if patients complained of shoulder pain, abdominal discomfort,
      nausea or hypotension. RESULTS: Spinal anaesthesia was adequate for surgery with
      no operative difficulty in all the patients. Intraoperatively, two patients
      experienced right shoulder pain and received Fentanyl, one patient was given
      Midazolam for anxiety and two were given Ephedrine for hypotension. The
      postoperative period was uneventful. CONCLUSION: Spinal anaesthesia with
      Hyperbaric Bupivacaine and Fentanyl is adequate and safe for elective
      laparoscopic appendectomy in healthy patients but careful evaluation of the
      method is needed particularly in compromised cardio respiratory conditions.

PMID- 22412774
TI  - APACHE II scores as predictors of cardio pulmonary resuscitation outcome:
      Evidence from a tertiary care institute in a low-income country.
AB  - AIM: The aim of this study was to demonstrate that APACHE II scores can be used
      as a predictor of the cardio-pulmonary resuscitation (CPR) outcome in
      hospitalized patients. METHODS: A retrospective chart review of patients
      admitted, from 2002 to 2007, at the Aga Khan University Hospital, Karachi, was
      done for this study. Information was collected on 738 patients, constituting all
      adults admitted in general ward, ICU, CICU and SCU during this time, and who had
      under-went cardiac arrest and received cardiopulmonary resuscitation during their
      stay at the hospital. Patient characteristics, intra-arrest variables such as
      event-witnessed, initial cardiac rhythm, pre arrest need for intubation and
      vasoactive drugs, duration of CPR and survival details were extracted from
      patient records. The APACHE II score was calculated for each patient and a
      descriptive analysis was done for demographic and clinical features. The primary
      outcome of successful CPR was categorized as survival >24 h after CPR versus
      survival <24 h after CPR. Multivariable logistic regression was used to assess
      the association between the explanatory variables and successful CPR. RESULTS:
      Patients with APACHE II scores less than 20 had 4.6 times higher odds of survival
      compared to patients with a score of >35 (AOR: 4.6, 95% CI: 2.4-9.0). Also,
      shorter duration of CPR (AOR: 2.9, 95% CI: 1.9-4.4), evening shift (AOR: 2.1, 95%
      CI: 1.3-3.5) and Male patients (AOR: 0.6, 95% CI: (0.4-0.9) compared to females
      were other significant predictors of CPR outcome. CONCLUSION: APACHE II score,
      along with other patient characteristics, should be considered in clinical
      decisions related to CPR administration.

PMID- 22412775
TI  - Epidural analgesia during labor vs no analgesia: A comparative study.
AB  - BACKGROUND: Epidural analgesia is claimed to result in prolonged labor. Previous
      studies have assessed epidural analgesia vs systemic opioids rather than to
      parturients receiving no analgesia. This study aimed to evaluate the effect of
      epidural analgesia on labor duration compared with parturients devoid of
      analgesia. METHODS: One hundred sixty nulliparous women in spontaneous labor at
      full term with a singleton vertex presentation were assigned to the study.
      Parturients who request epidural analgesia were allocated in the epidural group,
      whereas those not enthusiastic to labor analgesia were allocated in the control
      group. Epidural analgesia was provided with 20 mL bolus 0.5% epidural lidocaine
      plus fentanyl and maintained at 10 mL for 1 h. Duration of the first and second
      stages of labor, number of parturients receiving oxytocin, maximal oxytocin dose
      required for each parturient, numbers of instrumental vaginal, vacuum-assisted,
      and cesarean deliveries and neonatal Apgar score were recorded. RESULTS: There
      was no statistical difference in the duration of the active-first and the second
      stages of labor, instrumental delivery, vacuum-assisted or cesarean delivery
      rates, the number of newborns with 1-min and 5-min Apgar scores less than 7
      between both groups and number of parturients receiving oxytocin, however, the
      maximal oxytocin dose was significantly higher in the epidural group. CONCLUSION:
      Epidural analgesia by lidocaine (0.5%) and fentanyl does not prolong labor
      compared with parturients without analgesia; however, significant oxytocin
      augmentation is required during the epidural analgesia to keep up the
      aforementioned average labor duration.

PMID- 22412776
TI  - Efficacy of tranexamic acid on blood loss during bimaxilary osteotomy: A
      randomized double blind clinical trial.
AB  - BACKGROUND: Tranexamic acid has been used to reduce bleeding and the subsequent
      need for blood transfusion in many surgeries. Because orthognathic surgery can be
      associated with significant bleeding, this study evaluated the efficacy of
      prophylactic intravenous (IV) tranexamic acid on blood loss during bimaxillary
      osteotomy. METHODS: Thirty-two consecutive patients, scheduled for elective
      bimaxillary osteotomy, were included in the study and 16 were randomly assigned
      to each group. They received tranexamic acid (20 mg/kg) or equal volume of
      placebo (normal saline) intravenously just before induction of anesthesia.
      Intraoperative blood loss, pre and post operative hemoglobin (Hb) and hematocrit
      (Hct) concentration, duration of surgery, hospital stay time, and rate of blood
      transfusion were recorded for each patient. RESULTS: Intraoperative blood loss in
      the tranexamic group and control group were 585.9 and 790 mL respectively
      (P=0.008). Postoperative Hb concentration at the 6(th) hour was greater in the
      tranexamic group (P=0.008). There was no significant difference in the Hct
      concentration between the study groups. There was no significant difference in
      blood transfusion rate, hospital stay time and duration of surgery between the
      study groups. CONCLUSION: Preoperative IV administration of tranexamic acid
      reduces the amount of blood loss during bimaxillary osteotomy.

PMID- 22412778
TI  - Suprascapular nerve block for the treatment of frozen shoulder.
AB  - AIMS: The aim of our study was to compare the effects of suprascapular nerve
      block in patients with frozen shoulder and diabetes mellitus unresponsive to
      intraarticular steroid injections. SETTINGS AND DESIGN: Ten patients without
      improvement of sign and symptoms after intraarticular injections were made a
      suprascapular nerve block. METHODS: Pain levels and active range of movement of
      patients were recorded at initial attendance and after 1, 4, and 12 weeks. All
      patients' simple pain scores, total pain scores, and range of motion of their
      shoulders were improved significantly after suprascapular nerve block.
      STATISTICAL ANALYSIS: In this study, the statistical analyses were performed by
      using the SPSS 8.0 program (SPSS Software, SPSS Inc., USA). To compare pre- and
      post-injection results of simple pain score, total pain score, shoulder abduction
      and external rotation, Wilcoxon test was used. RESULTS: Patient's simple pain
      scores, total pain scores also abduction, external rotation and internal rotation
      angles were improved significantly after suprascapular nerve block. CONCLUSION:
      Effective results after suprascapular nerve blockage was obtained for the
      treatment of refractory frozen shoulder cases.

PMID- 22412777
TI  - Job burnout in 159 anesthesiology trainees.
AB  - BACKGROUND: Anesthesiology may be stressful and most anesthesiologists develop
      mechanisms for coping. However, inexperienced trainee anesthesiologists seem to
      be vulnerable. We studied stress perception and job burnout in trainee
      anesthesiologists. METHODS: Responses to perceived stress scale (PSS) and Maslach
      Burnout Inventory (MBI) were evaluated in 159 trainee anesthesiologists. RESULTS:
      In our results, when perceived stress was increased, emotional exhaustion and
      depersonalization increased but personal accomplishment decreased, as expected.
      Perceived stress was very high in the early years of training. There was a
      negative correlation between age and emotional exhaustion and depersonalization,
      but positive correlation with personal accomplishment. Female anesthesiologists
      had higher personal accomplishment, but lower depersonalization points than male
      anesthesiologists in our study. There was no statistical association between
      marital status, PSS, and MBI; >=2 children group had a significant high personal
      accomplishment but low depersonalization and emotional exhaustion scores. Line
      regression analysis showed a statistically significant relationship between PSS
      and emotional exhaustion and between age and depersonalization. CONCLUSIONS:
      Social factors such as gender and number of children affect the work life of our
      trainees.

PMID- 22412779
TI  - Assessment of the hemodynamic changes following fluid preloading in cardiac
      surgery.
AB  - BACKGROUND: This prospective double-blind randomized study aims to study the
      hemodynamic changes following fluid preloading with Hydroxyethyl starch (HES) 6%
      (130/0.4) compared with normal saline (NS) in cardiac surgery patients. METHODS:
      Forty patients undergoing coronary artery bypass grafting (CABG) were enrolled in
      this study, then they were divided in 2 equal groups, HES and NS. After fast
      administration of 10 mL/kg from either solutions over 5 min only, hemodynamic
      parameters, such as heart rate, mean arterial pressure (MAP), central venous
      pressure (CVP), pulmonary artery occlusion pressure (PAOP), mean pulmonary artery
      pressure, systemic vascular resistance, and pulmonary vascular resistance were
      measured every 5 min for the total duration of 40 minutes. RESULTS: There were
      significant differences in the cardiac index measurements between both groups at
      15 min onward; also PAOP was significantly higher in HES group at 10 min onward.
      CVP was higher in HES group but statistically significant at 10 min only. MAP was
      higher in HES group, but that was statistically significant at 40 min only. On
      the other hand PAP was significantly higher at 10 and 40 min. CONCLUSION: Fluid
      preloading with HES led to a significant increase in filling pressure of the left
      ventricle (PAOP) and cardiac index compared with NS. We believe that HES
      (130/0.4) could be a suitable solution for fluid preloading in CABG surgery
      patients. However, further studies are needed on different fluid preloading
      modalities with different dosing regimens.

PMID- 22412780
TI  - Imaging of sharp foreign body closer to the ulnar nerve using ultrasonography.
AB  - We report here the management of glass fragment buried in the soft tissue close
      to the ulnar nerve. Also discuss how ultrasound provides real-time guidance
      without radiation exposure and emphasize the importance of this evolving and
      exciting imaging field.

PMID- 22412781
TI  - Unusual diagnosis of a persistent third-degree atrioventricular block during
      anesthesia in a "healthy" pediatric patient.
AB  - We present an unusual diagnosis of a permanent third-degree atrioventricular
      block under general anesthesia in an otherwise healthy and asymptomatic child.
      This diagnosis of unclear causality represented a serious rare finding, requiring
      judicious management and resulting in the placement of a permanent pacemaker.

PMID- 22412782
TI  - Foreign body aspiration pneumonia in an intravenous drug user.
AB  - Heroin use is associated with several well described respiratory complications,
      including noncardiogenic pulmonary edema, aspiration pneumonitis, acute
      respiratory distress syndrome,pneumonia, lung abscess, septic pulmonary emboli,
      and atelectasis. We describe an interesting case of a young female patient, an
      intravenous heroin user who presented with progressive dyspnea, hypoxia, and left
      lung consolidation.

PMID- 22412783
TI  - Carinal injury: An airway challenge for anesthesiologists.
AB  - Tracheobronchial disruption is a potentially life-threatening airway challenge
      for all the anesthesiologists. Carinal rents, although rare, if not timely
      managed can be catastrophic. We describe a patient with carinal rent being
      managed successfully by prompt diagnosis, use of low pressure ventilation, and
      bronchoscopic sealing using tissue glue.

PMID- 22412784
TI  - Cholecystectomy under segmental thoracic epidural block in a patient with twin
      gestation.
AB  - Cholecystectomy represents the second most common surgery during pregnancy. Both
      general and regional anesthetic techniques have been successfully used for
      cholecystectomy in pregnant patients. Authors present here a case of a pregnant
      patient carrying twin gestation who underwent cholecystectomy, which is not
      frequently encountered by the anesthesiologists. This report enumerates the
      perioperative issues relating to anesthesia given to a pregnant patient in
      addition to emphasizing the importance of multidisciplinary approach when such a
      case is encountered.

PMID- 22412785
TI  - Anesthetic concerns in patients with abnormal migration of ventriculoperitoneal
      shunt.

PMID- 22412786
TI  - An innovative pediatric Y-connector to minimize dead space, and maximize safety
      and surgical access.

PMID- 22412787
TI  - Postoperative lingual edema is not always a predictor of airway compromise.

PMID- 22412788
TI  - Plagiarism: Intention more important than duplication.

PMID- 22412789
TI  - Persistent electrocardiogram changes during excision of craniopharyngioma.

PMID- 22412790
TI  - Changes in bispectral index values can predict post-ictal phase during awake
      craniotomy.

PMID- 22412791
TI  - Anesthetic problems in patient with paralyzed and pulse less extremity: A case of
      aortoarteritis.

PMID- 22412792
TI  - Macroglossia in a child undergoing posterior fossa surgery in sitting position.

PMID- 22412793
TI  - Malignant hyperthermia-like episode in a child with Larsen syndrome.

PMID- 22412794
TI  - A case of polycythemia vera for orthopedic surgery: Perianesthetic
      considerations.

PMID- 22412795
TI  - Propofol may be useful in patients with congenital dystonia syndrome undergoing
      magnetic resonance imaging.

PMID- 22412796
TI  - Unusual difficulty during central venous catheterization.

PMID- 22412797
TI  - A modified tracheal tube with curvature-control function for blind nasotracheal
      intubation.

PMID- 22412798
TI  - Myocardial ischemia during carotid artery stenting in neuroradiologic suite.

PMID- 22412799
TI  - Seizure during embolization of arteriovenous malformation.

PMID- 22412800
TI  - Recruitment of glycosyl hydrolase proteins in a cone snail venomous arsenal:
      further insights into biomolecular features of Conus venoms.
AB  - Cone snail venoms are considered an untapped reservoir of extremely diverse
      peptides, named conopeptides, displaying a wide array of pharmacological
      activities. We report here for the first time, the presence of high molecular
      weight compounds that participate in the envenomation cocktail used by these
      marine snails. Using a combination of proteomic and transcriptomic approaches, we
      identified glycosyl hydrolase proteins, of the hyaluronidase type (Hyal), from
      the dissected and injectable venoms ("injectable venom" stands for the venom
      variety obtained by milking of the snails. This is in contrast to the "dissected
      venom", which was obtained from dissected snails by extraction of the venom
      glands) of a fish-hunting cone snail, Conus consors (Pionoconus clade). The major
      Hyal isoform, Conohyal-Cn1, is expressed as a mixture of numerous glycosylated
      proteins in the 50 kDa molecular mass range, as observed in 2D gel and mass
      spectrometry analyses. Further proteomic analysis and venom duct mRNA sequencing
      allowed full sequence determination. Additionally, unambiguous segment location
      of at least three glycosylation sites could be determined, with glycans
      corresponding to multiple hexose (Hex) and N-acetylhexosamine (HexNAc) moieties.
      With respect to other known Hyals, Conohyal-Cn1 clearly belongs to the hydrolase
      type of Hyals, with strictly conserved consensus catalytic donor and positioning
      residues. Potent biological activity of the native Conohyals could be confirmed
      in degrading hyaluronic acid. A similar Hyal sequence was also found in the venom
      duct transcriptome of C. adamsonii (Textilia clade), implying a possible
      widespread recruitment of this enzyme family in fish-hunting cone snail venoms.
      These results provide the first detailed Hyal sequence characterized from a cone
      snail venom, and to a larger extent in the Mollusca phylum, thus extending our
      knowledge on this protein family and its evolutionary selection in marine snail
      venoms.

PMID- 22412802
TI  - New cytotoxic cembranolides from the soft coral Lobophytum michaelae.
AB  - Six new cembranolides, michaolides L-Q (1-6), and a known cembranolide,
      lobomichaolide (7) were isolated from the CH2Cl2 extract of the soft coral
      Lobophytum michaelae. Their structures were established by extensive spectral
      analysis. The anti-HCMV (human cytomegalovirus) activity of 1-7 and their
      cytotoxicity against selected cell lines were evaluated.

PMID- 22412801
TI  - Tetrodotoxin (TTX) as a therapeutic agent for pain.
AB  - Tetrodotoxin (TTX) is a potent neurotoxin that blocks voltage-gated sodium
      channels (VGSCs). VGSCs play a critical role in neuronal function under both
      physiological and pathological conditions. TTX has been extensively used to
      functionally characterize VGSCs, which can be classified as TTX-sensitive or TTX
      resistant channels according to their sensitivity to this toxin. Alterations in
      the expression and/or function of some specific TTX-sensitive VGSCs have been
      implicated in a number of chronic pain conditions. The administration of TTX at
      doses below those that interfere with the generation and conduction of action
      potentials in normal (non-injured) nerves has been used in humans and
      experimental animals under different pain conditions. These data indicate a role
      for TTX as a potential therapeutic agent for pain. This review focuses on the
      preclinical and clinical evidence supporting a potential analgesic role for TTX.
      In addition, the contribution of specific TTX-sensitive VGSCs to pain is
      reviewed.

PMID- 22412803
TI  - Five new amicoumacins isolated from a marine-derived bacterium Bacillus subtilis.
AB  - Four novel amicoumacins, namely lipoamicoumacins A-D (1-4), and one new
      bacilosarcin analog (5) were isolated from culture broth of a marine-derived
      bacterium Bacillus subtilis, together with six known amicoumacins. Their
      structures were elucidated on the basis of extensive spectroscopic (2D NNR, IR,
      CD and MS) analysis and in comparison with data in literature.

PMID- 22412804
TI  - Toxicity of cultured bullseye puffer fish Sphoeroides annulatus.
AB  - The toxin content in various life cycle stages of tank-cultivated bullseye puffer
      (Sphoeroides annulatus) were analyzed by mouse bioassay and ESI-MS spectrometry
      analysis. The presence of toxin content was determined in extracts of sperm,
      eggs, embryo, larvae, post-larvae, juvenile, pre-adult, and adult fish, as well
      as in food items used during the cultivation of the species. Our findings show
      that only the muscle of juveniles, the viscera of pre-adults, and muscle, liver,
      and gonad of adult specimens were slightly toxic (<1 mouse unit). Thus,
      cultivated S. annulatus, as occurs with other cultivated puffer fish species,
      does not represent a food safety risk to consumers. This is the first report of
      toxin analysis covering the complete life stages of a puffer fish under
      controlled conditions.

PMID- 22412805
TI  - Four eremophilane sesquiterpenes from the mangrove endophytic fungus Xylaria sp.
      BL321.
AB  - Three new eremophilane sesquiterpenes (1-3) were isolated from the mangrove
      endophytic fungus Xylaria sp. BL321 together with 07H239-A (4), a known analogue
      of the new compounds. The structures of these compounds were elucidated by
      analysis of their MS, 1D and 2D NMR spectroscopic data. Compound 4 showed
      activation activity on alpha-glucosidase at 0.15 MUM (146%), and then, 4
      gradually produced inhibitory activity on alpha-glucosidase with increasing
      concentration, and the IC50 value is 6.54 MUM.

PMID- 22412806
TI  - Two new tryptamine derivatives, leptoclinidamide and (-)-leptoclinidamine B, from
      an Indonesian ascidian Leptoclinides dubius.
AB  - Two new tryptamine-derived alkaloids, named as leptoclinidamide (1) and (-)
      leptoclinidamine B (2), were isolated from an Indonesian ascidian Leptoclinides
      dubius together with C2-alpha-D-mannosylpyranosyl-L-tryptophan (3). The structure
      of 1 was assigned on the basis of spectroscopic data for 1 and its N-acetyl
      derivative (4). Compound 1 was an amide of tryptamine with two beta-alanine
      units. Although the planar structure of 2 is identical to that of the known
      compound (+)-leptoclinidamine B (5), compound 2 was determined to be the
      enantiomer of 5 based on amino acid analysis using HPLC methods. Compounds 1 to 4
      were evaluated for cytotoxicity against two human cancer cell lines, HCT-15
      (colon) and Jurkat (T-cell lymphoma) cells, but none of the compounds showed
      activity.

PMID- 22412808
TI  - Antioxidant activity of Hawaiian marine algae.
AB  - Marine algae are known to contain a wide variety of bioactive compounds, many of
      which have commercial applications in pharmaceutical, medical, cosmetic,
      nutraceutical, food and agricultural industries. Natural antioxidants, found in
      many algae, are important bioactive compounds that play an important role against
      various diseases and ageing processes through protection of cells from oxidative
      damage. In this respect, relatively little is known about the bioactivity of
      Hawaiian algae that could be a potential natural source of such antioxidants. The
      total antioxidant activity of organic extracts of 37 algal samples, comprising of
      30 species of Hawaiian algae from 27 different genera was determined. The
      activity was determined by employing the FRAP (Ferric Reducing Antioxidant Power)
      assays. Of the algae tested, the extract of Turbinaria ornata was found to be the
      most active. Bioassay-guided fractionation of this extract led to the isolation
      of a variety of different carotenoids as the active principles. The major
      bioactive antioxidant compound was identified as the carotenoid fucoxanthin.
      These results show, for the first time, that numerous Hawaiian algae exhibit
      significant antioxidant activity, a property that could lead to their application
      in one of many useful healthcare or related products as well as in
      chemoprevention of a variety of diseases including cancer.

PMID- 22412807
TI  - Synthetic strategies to terpene quinones/hydroquinones.
AB  - The cytotoxic and antiproliferative properties of many natural sesquiterpene
      quinones and -hydroquinones from sponges offer promising opportunities for the
      development of new drugs. A review dealing with different strategies for
      obtaining bioactive terpenyl quinones/hydroquinones is presented. The different
      synthetic approches for the preparation of the most relevant
      quinones/hydroquinones are described.

PMID- 22412809
TI  - Antihypertensive effect of long-term oral administration of jellyfish (Rhopilema
      esculentum) collagen peptides on renovascular hypertension.
AB  - Antihypertensive effect of long-term oral administration of jellyfish (Rhopilema
      esculentum) collagen peptides (JCP) on renovascular hypertension rats (RVHs) was
      evaluated. The systolic blood pressure and diastolic blood pressure of the RVHs
      were significantly reduced with administration of JCP (p < 0.05), compared with
      model control group. However, the arterial blood pressure of normal rats showed
      no significant changes during long-term oral treatment with high dose JCP (p >
      0.05). Furthermore, effect of JCP on angiotensin II (Ang II) concentration of
      plasma had no significance (p > 0.05), but JCP significantly inhibited the Ang II
      concentration in RVHs' kidney (p < 0.05). The kidney should be the target site of
      JCP.

PMID- 22412810
TI  - Terpenoids from the octocorals Menella sp. (Plexauridae) and Lobophytum crassum
      (Alcyonacea).
AB  - A new germacrane-type sesquiterpenoid, menelloide E (1), and a new cembrane-type
      diterpenoid, lobocrassin F (2), were isolated from the octocorals Menella sp. and
      Lobophytum crassum, respectively. The structures of terpenoids 1 and 2 were
      determined by spectroscopic and chemical methods and compound 2 was found to
      display a significant inhibitory effect on the release of elastase by human
      neutrophils.

PMID- 22412811
TI  - Steroids from the soft coral Sinularia crassa.
AB  - One new sterol, crassarosterol A (1), and four new steroidal glycosides,
      crassarosterosides A-D (2-5) were isolated from the Formosan soft coral Sinularia
      crassa. The absolute configuration of 1 was determined using the Mosher's method.
      The absolute configurations for the sugar moieties of 2-5 were determined by HPLC
      analysis on the o-tolylthiocarbamates derived from the liberated sugar after acid
      hydrolysis. Compounds 2 and 4 could significantly inhibit the expression of pro
      inflammatory iNOS protein at 10 uM. In contrast, 1-3 were found to stimulate the
      expression of COX-2 protein at this concentration. Steroids 1 and 4 also showed
      cytotoxicity toward the selected human liver cancer cells.

PMID- 22412813
TI  - Anti-melanogenic property of geoditin A in murine B16 melanoma cells.
AB  - Geoditin A, an isomalabaricane triterpene isolated from marine sponge Geodia
      japonica, has been demonstrated to induce apoptosis in leukemia HL60 cells and
      human colon HT29 cancer cells through an oxidative stress, a process also
      interfering with normal melanogenesis in pigment cells. Treatment of murine
      melanoma B16 cells with geoditin A decreased expression of melanogenic proteins
      and cell melanogenesis which was aggravated with adenylate cyclase inhibitor
      SQ22536, indicating melanogenic inhibition was mediated through a cAMP-dependent
      signaling pathway. Immunofluorescence microscopy and glycosylation studies
      revealed abnormal glycosylation patterns of melanogenic proteins (tyrosinase and
      tyrosinase-related protein 1), and a co-localization of tyrosinase with calnexin
      (CNX) and lysosome-associated membrane protein 1 (LAMP-1), implicating a post
      translational modification in the ER and a degradation of tyrosinase in the
      lysosome. Taken together, potent anti-melanogenic property and the relatively low
      cytotoxicity of geoditin A have demonstrated its therapeutic potential as a skin
      lightening agent.

PMID- 22412812
TI  - Novel marine phenazines as potential cancer chemopreventive and anti-inflammatory
      agents.
AB  - Two new (1 and 2) and one known phenazine derivative (lavanducyanin, 3) were
      isolated and identified from the fermentation broth of a marine-derived
      Streptomyces sp. (strain CNS284). In mammalian cell culture studies, compounds 1,
      2 and 3 inhibited TNF-alpha-induced NFkappaB activity (IC50 values of 4.1, 24.2,
      and 16.3 MUM, respectively) and LPS-induced nitric oxide production (IC50 values
      of >48.6, 15.1, and 8.0 MUM, respectively). PGE2 production was blocked with
      greater efficacy (IC50 values of 7.5, 0.89, and 0.63 MUM, respectively), possibly
      due to inhibition of cyclooxygenases in addition to the expression of COX-2.
      Treatment of cultured HL-60 cells led to dose-dependent accumulation in the subG1
      compartment of the cell cycle, as a result of apoptosis. These data provide
      greater insight on the biological potential of phenazine derivatives, and some
      guidance on how various substituents may alter potential anti-inflammatory and
      anti-cancer effects.

PMID- 22412814
TI  - Ovatoxin-a and palytoxin accumulation in seafood in relation to Ostreopsis cf.
      ovata blooms on the French Mediterranean coast.
AB  - Dinoflagellates of the genus Ostreopsis are known to cause (often fatal) food
      poisoning in tropical coastal areas following the accumulation of palytoxin
      (PLTX) and/or its analogues (PLTX group) in crabs, sea urchins or fish.
      Ostreopsis spp. occurrence is presently increasing in the northern to north
      western Mediterranean Sea (Italy, Spain, Greece and France), probably in response
      to climate change. In France, Ostreopsis. cf. ovata has been associated with
      toxic events during summer 2006, at Morgiret, off the coast of Marseille, and a
      specific monitoring has been designed and implemented since 2007. Results from
      2008 and 2009 showed that there is a real danger of human poisoning, as these
      demonstrated bioaccumulation of the PLTX group (PLTX and ovatoxin-a) in both
      filter-feeding bivalve molluscs (mussels) and herbivorous echinoderms (sea
      urchins). The total content accumulated in urchins reached 450 ug PLTX eq/kg
      total flesh (summer 2008). In mussels, the maximum was 230 ug eq PLTX/kg (summer
      2009) compared with a maximum of 360 ug found in sea urchins during the same
      period at the same site. This publication brings together scientific knowledge
      obtained about the summer development of Ostreopsis spp. in France during 2007,
      2008 and 2009.

PMID- 22412815
TI  - A sterol and spiroditerpenoids from a Penicillium sp. isolated from a deep sea
      sediment sample.
AB  - A new polyoxygenated sterol, sterolic acid (1), three new breviane
      spiroditerpenoids, breviones I-K (2-4), and the known breviones (5-8), were
      isolated from the crude extract of a Penicillium sp. obtained from a deep sea
      sediment sample that was collected at a depth of 5115 m. The structures of 1-4
      were elucidated primarily by NMR experiments, and 1 was further confirmed by X
      ray crystallography. The absolute configurations of 2 and 3 were deduced by
      comparison of their CD spectra with those of the model compounds. Compounds 2 and
      5 showed significant cytotoxicity against MCF-7 cells, which is comparable to the
      positive control cisplatin.

PMID- 22412817
TI  - Reversible pulmonary hypertension related to thalidomide treatment for multiple
      myeloma.
AB  - Multiple myeloma (MM) is thrombogenic as a consequence of multiple hemostatic
      effects. Thalidomide is an effective treatment; however, it has been associated
      with an increased risk of thromboembolic events including pulmonary hypertension
      (PH). PH in the absence of thromboembolic events has also been described in some
      patients with MM during thalidomide treatment. We experienced occurrence of PH in
      a MM patient during treatment with thalidomide. A 79-year-old woman was diagnosed
      with IgG lambda MM and was started on thalidomide treatment. About a month later,
      she presented with asthenia, palpitation and dyspnoea on exertion and was
      hospitalized. An echocardiography revealed severe PH (systolic pulmonary artery
      pressure 75 mm Hg) without paradoxic movement of ventricular septum or right
      ventricular dysfunction signs; a previous echocardiography was normal. Pulmonary
      computed tomography and perfusion scan were negative for pulmonary embolism.
      Based on the hypothesis of a pharmacological pathogenesis, thalidomide was
      promptly interrupted. About a month later, she was hospitalized for further
      investigations. Physical examination documented absence of dyspnoea or other
      respiratory signs, and echocardiography showed normal right ventricular function
      and normal pulmonary artery pressure. As in the cases reported in the literature,
      we suggest a possible direct correlation between thalidomide and PH, since in all
      cases a rapid decrease of pulmonary artery pressure after thalidomide
      discontinuation was observed.

PMID- 22412816
TI  - Cyanobacterial neurotoxin beta-N-methylamino-L-alanine (BMAA) in shark fins.
AB  - Sharks are among the most threatened groups of marine species. Populations are
      declining globally to support the growing demand for shark fin soup. Sharks are
      known to bioaccumulate toxins that may pose health risks to consumers of shark
      products. The feeding habits of sharks are varied, including fish, mammals,
      crustaceans and plankton. The cyanobacterial neurotoxin beta-N-methylamino-L
      alanine (BMAA) has been detected in species of free-living marine cyanobacteria
      and may bioaccumulate in the marine food web. In this study, we sampled fin clips
      from seven different species of sharks in South Florida to survey the occurrence
      of BMAA using HPLC-FD and Triple Quadrupole LC/MS/MS methods. BMAA was detected
      in the fins of all species examined with concentrations ranging from 144 to 1836
      ng/mg wet weight. Since BMAA has been linked to neurodegenerative diseases, these
      results may have important relevance to human health. We suggest that consumption
      of shark fins may increase the risk for human exposure to the cyanobacterial
      neurotoxin BMAA.

PMID- 22412818
TI  - Involvement of bone in epithelial ovarian cancer: case report of an uncommon late
      metastatic event.
AB  - Bone involvement is uncommon in epithelial ovarian cancer. In this report, a case
      of bone metastases from ovarian cancer is described and the potential risk
      factors for such a rare occurrence are discussed. It is possible that such an
      event will become more common in the future as patients with advanced ovarian
      cancer experience prolonged survival but the cancer is not eliminated.

PMID- 22412829
TI  - Multiple frequencies sequential coding for SSVEP-based brain-computer interface.
AB  - BACKGROUND: Steady-state visual evoked potential (SSVEP)-based brain-computer
      interface (BCI) has become one of the most promising modalities for a practical
      noninvasive BCI system. Owing to both the limitation of refresh rate of liquid
      crystal display (LCD) or cathode ray tube (CRT) monitor, and the specific
      physiological response property that only a very small number of stimuli at
      certain frequencies could evoke strong SSVEPs, the available frequencies for
      SSVEP stimuli are limited. Therefore, it may not be enough to code multiple
      targets with the traditional frequencies coding protocols, which poses a big
      challenge for the design of a practical SSVEP-based BCI. This study aimed to
      provide an innovative coding method to tackle this problem. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we present a novel protocol termed multiple frequencies
      sequential coding (MFSC) for SSVEP-based BCI. In MFSC, multiple frequencies are
      sequentially used in each cycle to code the targets. To fulfill the sequential
      coding, each cycle is divided into several coding epochs, and during each epoch,
      certain frequency is used. Obviously, different frequencies or the same frequency
      can be presented in the coding epochs, and the different epoch sequence
      corresponds to the different targets. To show the feasibility of MFSC, we used
      two frequencies to realize four targets and carried on an offline experiment. The
      current study shows that: 1) MFSC is feasible and efficient; 2) the performance
      of SSVEP-based BCI based on MFSC can be comparable to some existed systems.
      CONCLUSIONS/SIGNIFICANCE: The proposed protocol could potentially implement much
      more targets with the limited available frequencies compared with the traditional
      frequencies coding protocol. The efficiency of the new protocol was confirmed by
      real data experiment. We propose that the SSVEP-based BCI under MFSC might be a
      promising choice in the future.

PMID- 22412830
TI  - Adaptive and phase selective spike timing dependent plasticity in synaptically
      coupled neuronal oscillators.
AB  - We consider and analyze the influence of spike-timing dependent plasticity (STDP)
      on homeostatic states in synaptically coupled neuronal oscillators. In contrast
      to conventional models of STDP in which spike-timing affects weights of synaptic
      connections, we consider a model of STDP in which the time lags between pre-
      and/or post-synaptic spikes change internal state of pre- and/or post-synaptic
      neurons respectively. The analysis reveals that STDP processes of this type,
      modeled by a single ordinary differential equation, may ensure efficient, yet
      coarse, phase-locking of spikes in the system to a given reference phase.
      Precision of the phase locking, i.e. the amplitude of relative phase deviations
      from the reference, depends on the values of natural frequencies of oscillators
      and, additionally, on parameters of the STDP law. These deviations can be
      optimized by appropriate tuning of gains (i.e. sensitivity to spike-timing
      mismatches) of the STDP mechanism. However, as we demonstrate, such deviations
      can not be made arbitrarily small neither by mere tuning of STDP gains nor by
      adjusting synaptic weights. Thus if accurate phase-locking in the system is
      required then an additional tuning mechanism is generally needed. We found that
      adding a very simple adaptation dynamics in the form of slow fluctuations of the
      base line in the STDP mechanism enables accurate phase tuning in the system with
      arbitrary high precision. Adaptation operating at a slow time scale may be
      associated with extracellular matter such as matrix and glia. Thus the findings
      may suggest a possible role of the latter in regulating synaptic transmission in
      neuronal circuits.

PMID- 22412831
TI  - DNA repair in human pluripotent stem cells is distinct from that in non
      pluripotent human cells.
AB  - The potential for human disease treatment using human pluripotent stem cells,
      including embryonic stem cells and induced pluripotent stem cells (iPSCs), also
      carries the risk of added genomic instability. Genomic instability is most often
      linked to DNA repair deficiencies, which indicates that
      screening/characterization of possible repair deficiencies in pluripotent human
      stem cells should be a necessary step prior to their clinical and research use.
      In this study, a comparison of DNA repair pathways in pluripotent cells, as
      compared to those in non-pluripotent cells, demonstrated that DNA repair
      capacities of pluripotent cell lines were more heterogeneous than those of
      differentiated lines examined and were generally greater. Although pluripotent
      cells had high DNA repair capacities for nucleotide excision repair, we show that
      ultraviolet radiation at low fluxes induced an apoptotic response in these cells,
      while differentiated cells lacked response to this stimulus, and note that
      pluripotent cells had a similar apoptotic response to alkylating agent damage.
      This sensitivity of pluripotent cells to damage is notable since viable
      pluripotent cells exhibit less ultraviolet light-induced DNA damage than do
      differentiated cells that receive the same flux. In addition, the importance of
      screening pluripotent cells for DNA repair defects was highlighted by an iPSC
      line that demonstrated a normal spectral karyotype, but showed both
      microsatellite instability and reduced DNA repair capacities in three out of four
      DNA repair pathways examined. Together, these results demonstrate a need to
      evaluate DNA repair capacities in pluripotent cell lines, in order to
      characterize their genomic stability, prior to their pre-clinical and clinical
      use.

PMID- 22412833
TI  - Responses of fine roots and soil N availability to short-term nitrogen
      fertilization in a broad-leaved Korean pine mixed forest in northeastern China.
AB  - Knowledge of the responses of soil nitrogen (N) availability, fine root mass,
      production and turnover rates to atmospheric N deposition is crucial for
      understanding fine root dynamics and functioning in forest ecosystems. Fine root
      biomass and necromass, production and turnover rates, and soil nitrate-N and
      ammonium-N in relation to N fertilization (50 kg N ha(-1) year(-1)) were
      investigated in a temperate forest over the growing season of 2010, using
      sequential soil cores and ingrowth cores methods. N fertilization increased soil
      nitrate-N by 16% (P<0.001) and ammonium-N by 6% (P<0.01) compared to control
      plots. Fine root biomass and necromass in 0-20 cm soil were 13% (4.61 vs. 5.23 Mg
      ha(-1), P<0.001) and 34% (1.39 vs. 1.86 Mg ha(-1), P<0.001) less in N
      fertilization plots than those in control plots. The fine root mass was
      significantly negatively correlated with soil N availability and nitrate-N
      contents, especially in 0-10 cm soil layer. Both fine root production and
      turnover rates increased with N fertilization, indicating a rapid underground
      carbon cycling in environment with high nitrogen levels. Although high N supply
      has been widely recognized to promote aboveground growth rates, the present study
      suggests that high levels of nitrogen supply may reduce the pool size of the
      underground carbon. Hence, we conclude that high levels of atmospheric N
      deposition will stimulate the belowground carbon cycling, leading to changes in
      the carbon balance between aboveground and underground storage. The implications
      of the present study suggest that carbon model and prediction need to take the
      effects of nitrogen deposition on underground system into account.

PMID- 22412832
TI  - Autistic disorder in patients with Williams-Beuren syndrome: a reconsideration of
      the Williams-Beuren syndrome phenotype.
AB  - BACKGROUND: Williams-Beuren syndrome (WBS), a rare developmental disorder caused
      by deletion of contiguous genes at 7q11.23, has been characterized by strengths
      in socialization (overfriendliness) and communication (excessive talkativeness).
      WBS has been often considered as the polar opposite behavioral phenotype to
      autism. Our objective was to better understand the range of phenotypic expression
      in WBS and the relationship between WBS and autistic disorder. METHODOLOGY: The
      study was conducted on 9 French individuals aged from 4 to 37 years old with
      autistic disorder associated with WBS. Behavioral assessments were performed
      using Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic
      Observation Schedule (ADOS) scales. Molecular characterization of the WBS
      critical region was performed by FISH. FINDINGS: FISH analysis indicated that all
      9 patients displayed the common WBS deletion. All 9 patients met ADI-R and ADOS
      diagnostic criteria for autism, displaying stereotypies and severe impairments in
      social interaction and communication (including the absence of expressive
      language). Additionally, patients showed improvement in social communication over
      time. CONCLUSIONS: The results indicate that comorbid autism and WBS is more
      frequent than expected and suggest that the common WBS deletion can result in a
      continuum of social communication impairment, ranging from excessive
      talkativeness and overfriendliness to absence of verbal language and poor social
      relationships. Appreciation of the possible co-occurrence of WBS and autism
      challenges the common view that WBS represents the opposite behavioral phenotype
      of autism, and might lead to improved recognition of WBS in individuals diagnosed
      with autism.

PMID- 22412834
TI  - Phylo: a citizen science approach for improving multiple sequence alignment.
AB  - BACKGROUND: Comparative genomics, or the study of the relationships of genome
      structure and function across different species, offers a powerful tool for
      studying evolution, annotating genomes, and understanding the causes of various
      genetic disorders. However, aligning multiple sequences of DNA, an essential
      intermediate step for most types of analyses, is a difficult computational task.
      In parallel, citizen science, an approach that takes advantage of the fact that
      the human brain is exquisitely tuned to solving specific types of problems, is
      becoming increasingly popular. There, instances of hard computational problems
      are dispatched to a crowd of non-expert human game players and solutions are sent
      back to a central server. METHODOLOGY/PRINCIPAL FINDINGS: We introduce Phylo, a
      human-based computing framework applying "crowd sourcing" techniques to solve the
      Multiple Sequence Alignment (MSA) problem. The key idea of Phylo is to convert
      the MSA problem into a casual game that can be played by ordinary web users with
      a minimal prior knowledge of the biological context. We applied this strategy to
      improve the alignment of the promoters of disease-related genes from up to 44
      vertebrate species. Since the launch in November 2010, we received more than
      350,000 solutions submitted from more than 12,000 registered users. Our results
      show that solutions submitted contributed to improving the accuracy of up to 70%
      of the alignment blocks considered. CONCLUSIONS/SIGNIFICANCE: We demonstrate
      that, combined with classical algorithms, crowd computing techniques can be
      successfully used to help improving the accuracy of MSA. More importantly, we
      show that an NP-hard computational problem can be embedded in casual game that
      can be easily played by people without significant scientific training. This
      suggests that citizen science approaches can be used to exploit the billions of
      "human-brain peta-flops" of computation that are spent every day playing games.
      Phylo is available at: http://phylo.cs.mcgill.ca.

PMID- 22412835
TI  - Migration of Th1 lymphocytes is regulated by CD152 (CTLA-4)-mediated signaling
      via PI3 kinase-dependent Akt activation.
AB  - Efficient adaptive immune responses require the localization of T lymphocytes in
      secondary lymphoid organs and inflamed tissues. To achieve correct localization
      of T lymphocytes, the migration of these cells is initiated and directed by
      adhesion molecules and chemokines. It has recently been shown that the inhibitory
      surface molecule CD152 (CTLA-4) initiates Th cell migration, but the molecular
      mechanism underlying this effect remains to be elucidated. Using CD4 T
      lymphocytes derived from OVA-specific TCR transgenic CD152-deficient and CD152
      competent mice, we demonstrate that chemokine-triggered signal transduction is
      differentially regulated by CD152 via phosphoinositide 3-kinase (PI3K)-dependent
      activation of protein kinase B (PKB/Akt). In the presence of CD152 signaling, the
      chemoattractant CCL4 selectively induces the full activation of Akt via
      phosphorylation at threonine 308 and serine 473 in pro-inflammatory Th
      lymphocytes expressing the cognate chemokine receptor CCR5. Akt signals lead to
      cytoskeleton rearrangements, which are indispensable for migration. Therefore,
      this novel Akt-modulating function of CD152 signals affecting T cell migration
      demonstrates that boosting CD152 or its down-stream signal transduction could aid
      therapies aimed at sensitizing T lymphocytes for optimal migration, thus
      contributing to a precise and effective immune response.

PMID- 22412836
TI  - MRI of arterial flow reserve in patients with intermittent claudication:
      feasibility and initial experience.
AB  - OBJECTIVES: The aim of this work was to develop a MRI method to determine
      arterial flow reserve in patients with intermittent claudication and to
      investigate whether this method can discriminate between patients and healthy
      control subjects. METHODS: Ten consecutive patients with intermittent
      claudication and 10 healthy control subjects were included. All subjects
      underwent vector cardiography triggered quantitative 2D cine MR phase-contrast
      imaging to obtain flow waveforms of the popliteal artery at rest and during
      reactive hyperemia. Resting flow, maximum hyperemic flow and absolute flow
      reserve were determined and compared between the two groups by two independent
      MRI readers. Also, interreader reproducibility of flow measures was reported.
      RESULTS: Resting flow was lower in patients compared to controls (4.9+/-1.6 and
      11.1+/-3.2 mL/s in patients and controls, respectively (p<0.01)). Maximum
      hyperemic flow was 7.3+/-2.9 and 16.4+/-3.2 mL/s (p<0.01) and the absolute flow
      reserve was 2.4+/-1.6 and 5.3+/-1.3 mL/s (p<0.01), respectively in patients and
      controls. The interreader coefficient of variation was below 10% for all measures
      in both patients and controls. CONCLUSIONS: Quantitative 2D MR cine phase
      contrast imaging is a promising method to determine flow reserve measures in
      patients with peripheral arterial disease and can be helpful to discriminate
      patients with intermittent claudication from healthy controls.

PMID- 22412837
TI  - Pioglitazone decreases hepatitis C viral load in overweight, treatment naive,
      genotype 4 infected-patients: a pilot study.
AB  - BACKGROUND: Insulin resistance (IR) is induced by chronic hepatitis C virus (HCV)
      genotypes 1 and 4 infections. It is not known whether drugs that affect IR such
      as Pioglitazone and Prednisone also affect serum HCV RNA titers independently of
      PEG-Interferon-alpha2/ribavirin treatment. The primary aim was to assess whether
      Pioglitazone by improving IR and/or inflammation decreases HCV viral load
      independently of standard of care HCV treatment. A secondary aim was to assess
      whether Prednisone, a drug that induces insulin resistance and stimulates HCV
      viral entry and replication in replicon culture systems, increases HCV viral load
      in this population. METHODOLOGY/PRINCIPAL FINDINGS: We designed a two-arm,
      parallel Pilot Study of overweight, treatment naive genotype 4 HCV-infected
      patients at a public referral Liver Clinic in Giza, Egypt. The subjects received
      Pioglitazone (30 mg/day for 14 days) or Prednisone (40 mg/day for 4 days) in a
      randomized fashion, but the two arms can be considered independent pilot studies.
      Only changes from baseline within each arm were assessed and no contrasts of the
      interventions were made, as this was not an aim of the study. Among 105
      consecutive HCV genotype 4 patients, 39 were enrolled based on the optimal sample
      size and power analysis according to the CONSORT statement; 20 to the
      Pioglitazone group and 19 to the Prednisone group. Pioglitazone was effective in
      decreasing serum HCV RNA at day-14 (n = 10; difference of means = 205,618 IU/ml;
      95% CI 26,600 to 384,600; P<0.001). Although Prednisone did increase serum HCV
      RNA at day-4 (n = 10; change from baseline = -42,786 IU/ml; 95% CI -85,500 to 
      15,700; P = 0.049), the log(10) HCV RNA titers were statistically not different
      from baseline day-0. CONCLUSION/SIGNIFICANCE: This is the first documentation
      that Pioglitazone decreases the serum HCV RNA titers independently of PEG
      Interferon-alpha2/ribavirin treatment. The novel findings of our Study provide
      the foundation for basic and clinical investigations on the molecular mechanisms
      responsible for the Pioglitazone-induced decrease in HCV genotype 4 RNA titers.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01157975.

PMID- 22412838
TI  - Kinetics of proton transport into influenza virions by the viral M2 channel.
AB  - M2 protein of influenza A viruses is a tetrameric transmembrane proton channel,
      which has essential functions both early and late in the virus infectious cycle.
      Previous studies of proton transport by M2 have been limited to measurements
      outside the context of the virus particle. We have developed an in vitro
      fluorescence-based assay to monitor internal acidification of individual virions
      triggered to undergo membrane fusion. We show that rimantadine, an inhibitor of
      M2 proton conductance, blocks the acidification-dependent dissipation of
      fluorescence from a pH-sensitive virus-content probe. Fusion-pore formation
      usually follows internal acidification but does not require it. The rate of
      internal virion acidification increases with external proton concentration and
      saturates with a pK(m) of ~4.7. The rate of proton transport through a single,
      fully protonated M2 channel is approximately 100 to 400 protons per second. The
      saturating proton-concentration dependence and the low rate of internal virion
      acidification derived from authentic virions support a transporter model for the
      mechanism of proton transfer.

PMID- 22412839
TI  - Primary effusion lymphoma cell death induced by bortezomib and AG 490 activates
      dendritic cells through CD91.
AB  - To understand how cytotoxic agent-induced cancer cell death affects the immune
      system is of fundamental importance to stimulate immune response to counteract
      the high mortality due to cancer. Here we compared the immunogenicity of Primary
      Effusion Lymphoma (PEL) cell death induced by anticancer drug Bortezomib
      (Velcade) and Tyrphostin AG 490, a Janus Activated Kinase 2/signal trasducer and
      activator of transcription-3 (JAK2/STAT3) inhibitor. We show that both treatments
      were able to induce PEL apoptosis with similar kinetics and promote dendritic
      cells (DC) maturation. The surface expression of molecules involved in immune
      activation, namely calreticulin (CRT), heat shock proteins (HSP) 90 and 70
      increased in dying cells. This was correlated with DC activation. We found that
      PEL cell death induced by Bortezomib was more effective in inducing uptake by DC
      compared to AG 490 or combination of both drugs. However the DC activation
      induced by all treatments was completely inhibited when these cells were
      pretreated with a neutralizing antiboby directed against the HSP90/70 and CRT
      common receptor, CD91. The activation of DC by Bortezomib and AG 490 treated PEL
      cells, as seen in the present study, might have important implications for a
      combined chemo and immunotherapy in such patients.

PMID- 22412840
TI  - Survival from XDR-TB is associated with modifiable clinical characteristics in
      rural South Africa.
AB  - BACKGROUND: Drug-resistant tuberculosis (TB) is a major threat to global public
      health. Patients with extensively drug-resistant TB (XDR-TB), particularly those
      with HIV-coinfection, experience high and accelerated mortality with limited
      available interventions. To determine modifiable factors associated with
      survival, we evaluated XDR-TB patients from a community-based hospital in rural
      South Africa where a large number of XDR-TB cases were first detected.
      METHODOLOGY/PRINCIPAL FINDINGS: A retrospective case control study was conducted
      of XDR-TB patients diagnosed from 2005-2008. Survivors, those alive at 180 days
      from diagnostic sputum collection date, were compared with controls who died
      within 180 days. Clinical, laboratory and microbiological correlates of survival
      were assessed in 69 survivors (median survival 565 days [IQR 384-774] and 73 non
      survivors (median survival 34 days [IQR 18-90]). Among 129 HIV+ patients,
      multivariate analyses of modifiable factors demonstrated that negative AFB smear
      (AOR 8.4, CI 1.84-38.21), a lower laboratory index of routine laboratory findings
      (AOR 0.48, CI 0.22-1.02), CD4>200 cells/mm(3) (AOR 11.53, 1.1-119.32), and
      receipt of antiretroviral therapy (AOR 20.9, CI 1.16-376.83) were independently
      associated with survival from XDR-TB. CONCLUSIONS/SIGNIFICANCE: Survival from XDR
      TB with HIV-coinfection is associated with less advanced stages of both diseases
      at time of diagnosis, absence of laboratory markers indicative of multiorgan
      dysfunction, and provision of antiretroviral therapy. Survival can be increased
      by addressing these modifiable risk factors through policy changes and improved
      clinical management. Health planners and clinicians should develop programmes
      focusing on earlier case finding and integration of HIV and drug-resistant TB
      diagnostic, therapeutic, and preventive activities.

PMID- 22412841
TI  - 5-Fluorouracil induced intestinal mucositis via nuclear factor-kappaB activation
      by transcriptomic analysis and in vivo bioluminescence imaging.
AB  - 5-Fluorouracil (5-FU) is a commonly used drug for the treatment of malignant
      cancers. However, approximately 80% of patients undergoing 5-FU treatment suffer
      from gastrointestinal mucositis. The aim of this report was to identify the drug
      target for the 5-FU-induced intestinal mucositis. 5-FU-induced intestinal
      mucositis was established by intraperitoneally administering mice with 100 mg/kg
      5-FU. Network analysis of gene expression profile and bioluminescent imaging were
      applied to identify the critical molecule associated with 5-FU-induced mucositis.
      Our data showed that 5-FU induced inflammation in the small intestine,
      characterized by the increased intestinal wall thickness and crypt length, the
      decreased villus height, and the increased myeloperoxidase activity in tissues
      and proinflammatory cytokine production in sera. Network analysis of 5-FU
      affected genes by transcriptomic tool showed that the expression of genes was
      regulated by nuclear factor-kappaB (NF-kappaB), and NF-kappaB was the central
      molecule in the 5-FU-regulated biological network. NF-kappaB activity was
      activated by 5-FU in the intestine, which was judged by in vivo bioluminescence
      imaging and immunohistochemical staining. However, 5-aminosalicylic acid (5-ASA)
      inhibited 5-FU-induced NF-kappaB activation and proinflammatory cytokine
      production. Moreover, 5-FU-induced histological changes were improved by 5-ASA.
      In conclusion, our findings suggested that NF-kappaB was the critical molecule
      associated with the pathogenesis of 5-FU-induced mucositis, and inhibition of NF
      kappaB activity ameliorated the mucosal damage caused by 5-FU.

PMID- 22412842
TI  - Acute histologic chorioamnionitis at term: nearly always noninfectious.
AB  - BACKGROUND: The link between histologic acute chorioamnionitis and infection is
      well established in preterm deliveries, but less well-studied in term
      pregnancies, where infection is much less common. METHODOLOGY/PRINCIPAL FINDINGS:
      We conducted a secondary analysis among 195 low-risk women with term pregnancies
      enrolled in a randomized trial. Histologic and microbiologic evaluation of
      placentas included anaerobic and aerobic cultures (including
      mycoplasma/ureaplasma species) as well as PCR. Infection was defined as >=1,000
      cfu of a single known pathogen or a >=2 log difference in counts for a known
      pathogen versus other organisms in a mixed culture. Placental membranes were
      scored and categorized as: no chorioamnionitis, Grade 1 (subchorionitis and
      patchy acute chorioamnionitis), or Grade 2 (severe, confluent chorioamnionitis).
      Grade 1 or grade 2 histologic chorioamnionitis was present in 34% of placentas
      (67/195), but infection was present in only 4% (8/195). Histologic
      chorioamnionitis was strongly associated with intrapartum fever >38 degrees C
      [69% (25/36) fever, 26% (42/159) afebrile, P<.0001]. Fever occurred in 18% (n =
      36) of women. Most febrile women [92% (33/36)] had received epidural for pain
      relief, though the association with fever was present with and without epidural.
      The association remained significant in a logistic regression controlling for
      potential confounders (OR = 5.8, 95% CI = 2.2,15.0). Histologic chorioamnionitis
      was also associated with elevated serum levels of interleukin-8 (median = 1.3
      pg/mL no histologic chorioamnionitis, 1.5 pg/mL Grade 1, 2.1 pg/mL Grade 2, P =
      0.05) and interleukin-6 (median levels = 2.2 pg/mL no chorioamnionitis, 5.3 pg/mL
      Grade 1, 24.5 pg/mL Grade 2, P = 0.02) at admission for delivery as well as
      higher admission WBC counts (mean = 12,000 cells/mm(3) no chorioamnionitis,
      13,400 cells/mm(3) Grade 1, 15,700 cells/mm(3) Grade 2, P = 0.0005).
      CONCLUSION/SIGNIFICANCE: Our results suggest histologic chorioamnionitis at term
      most often results from a noninfectious inflammatory process. It was strongly
      associated with fever, most of which was related to epidural used for pain
      relief. A more 'activated' maternal immune system at admission was also
      associated with histologic chorioamnionitis.

PMID- 22412843
TI  - Prolyl isomerase Pin1 regulates mouse embryonic fibroblast differentiation into
      adipose cells.
AB  - BACKGROUND: A peptidyl prolyl cis/trans isomerase, Pin1, regulates insulin signal
      transduction. Pin1 reduces responses to insulin stimulation by binding CRTC2
      (CREB-regulated transcriptional co-activator 2) and PPARgamma (peroxisome
      prolifereator- activated receptor gamma), but conversely enhances insulin
      signaling by binding IRS-1 (insulin receptor substrate-1), Akt kinase, and Smad3.
      Therefore, it is still unclear whether Pin1 inhibits or enhances adipose cell
      differentiation. METHODOLOGY/PRINCIPAL FINDINGS: Pin1(-/-) and wild-type mice
      were fed with high fat diets and adipose tissue weight was measured. Compared to
      wild-type mice, Pin1(-/-) mice had lower adipose tissue weight, while the weight
      of other tissues was similar. Mouse embryo fibroblasts (MEFs), prepared from both
      groups of mice, were induced to differentiate into adipose cells by stimulation
      with insulin. However, the rate of differentiation of MEFs from Pin1(-/-) mice
      was less than that of MEFs from wild-type mice. The rate of insulin-induced MEF
      cell differentiation in Pin1(-/-) mice was restored by increasing expression of
      Pin1. We found that Pin1 binds to phosphoThr172- and phosphoSer271-Pro sites in
      CREB suppress the activity in COS-7 cells. CONCLUSION AND SIGNIFICANCE: Pin1
      enhanced the uptake of triglycerides and the differentiation of MEF cells into
      adipose cells in response to insulin stimulation. Results of this study suggest
      that Pin1 down-regulation could be a potential approach in obesity-related
      dysfunctions, such as high blood pressure, diabetes, non-alcoholic
      steatohepatitis.

PMID- 22412844
TI  - Species history masks the effects of human-induced range loss--unexpected genetic
      diversity in the endangered giant mayfly Palingenia longicauda.
AB  - Freshwater biodiversity has declined dramatically in Europe in recent decades.
      Because of massive habitat pollution and morphological degradation of water
      bodies, many once widespread species persist in small fractions of their original
      range. These range contractions are generally believed to be accompanied by loss
      of intraspecific genetic diversity, due to the reduction of effective population
      sizes and the extinction of regional genetic lineages. We aimed to assess the
      loss of genetic diversity and its significance for future potential
      reintroduction of the long-tailed mayfly Palingenia longicauda (Olivier), which
      experienced approximately 98% range loss during the past century. Analysis of 936
      bp of mitochondrial DNA of 245 extant specimens across the current range revealed
      a surprisingly large number of haplotypes (87), and a high level of haplotype
      diversity (Hd = 0.875). In contrast, historic specimens (6) from the lost range
      (Rhine catchment) were not differentiated from the extant Raba population (F(ST)
      = 0.02, p = 0.61), despite considerable geographic distance separating the two
      rivers. These observations can be explained by an overlap of the current with the
      historic (Pleistocene) refugia of the species. Most likely, the massive recent
      range loss mainly affected the range which was occupied by rapid post-glacial
      dispersal. We conclude that massive range losses do not necessarily coincide with
      genetic impoverishment and that a species' history must be considered when
      estimating loss of genetic diversity. The assessment of spatial genetic
      structures and prior phylogeographic information seems essential to conserve once
      widespread species.

PMID- 22412845
TI  - Deep sequencing for the detection of virus-like sequences in the brains of
      patients with multiple sclerosis: detection of GBV-C in human brain.
AB  - Multiple sclerosis (MS) is a demyelinating disease of unknown origin that affects
      the central nervous system of an estimated 400,000 Americans. GBV-C or hepatitis
      G is a flavivirus that is found in the serum of 1-2% of blood donors. It was
      originally associated with hepatitis, but is now believed to be a relatively non
      pathogenic lymphotropic virus. Fifty frozen specimens from the brains of deceased
      persons affected by MS were obtained along with 15 normal control brain
      specimens. RNA was extracted and ribosomal RNAs were depleted before sequencing
      on the Illumina GAII. These 36 bp reads were compared with a non-redundant
      database derived from the 600,000+ viral sequences in GenBank organized into 4080
      taxa. An individual read successfully aligned to the viral database was
      considered to be a "hit". Normalized MS specimen hit rates for each viral taxon
      were compared to the distribution of hits in the normal controls. Seventeen MS
      and 11 control brain extracts were sequenced, yielding 4-10 million sequences
      ("reads") each. Over-representation of sequence from at least one of 12 viral
      taxa was observed in 7 of the 17 MS samples. Sequences resembling other viruses
      previously implicated in the pathogenesis of MS were not significantly enriched
      in any of the diseased brain specimens. Sequences from GB virus C (GBV-C), a
      flavivirus not previously isolated from brain, were enriched in one of the MS
      samples. GBV-C in this brain specimen was confirmed by specific amplification in
      this single MS brain specimen, but not in the 30 other MS brain samples
      available. The entire 9.4 kb sequence of this GBV-C isolate is reported here.
      This study shows the feasibility of deep sequencing for the detection of occult
      viral infections in the brains of deceased persons with MS. The first isolation
      of GBV-C from human brain is reported here.

PMID- 22412846
TI  - Animal behavior frozen in time: gregarious behavior of Early Jurassic lobsters
      within an ammonoid body chamber.
AB  - Direct animal behavior can be inferred from the fossil record only in exceptional
      circumstances. The exceptional mode of preservation of ammonoid shells in the
      Posidonia Shale (Lower Jurassic, lower Toarcian) of Dotternhausen in southern
      Germany, with only the organic periostracum preserved, provides an excellent
      opportunity to observe the contents of the ammonoid body chamber because this
      periostracum is translucent. Here, we report upon three delicate lobsters
      preserved within a compressed ammonoid specimen of Harpoceras falciferum. We
      attempt to explain this gregarious behavior. The three lobsters were studied
      using standard microscopy under low angle light. The lobsters belong to the
      extinct family of the Eryonidae; further identification was not possible. The
      organic material of the three small lobsters is preserved more than halfway into
      the ammonoid body chamber. The lobsters are closely spaced and are positioned
      with their tails oriented toward each other. The specimens are interpreted to
      represent corpses rather than molts. The lobsters probably sought shelter in
      preparation for molting or against predators such as fish that were present in
      Dotternhausen. Alternatively, the soft tissue of the ammonoid may have been a
      source of food that attracted the lobsters, or it may have served as a long-term
      residency for the lobsters (inquilinism). The lobsters represent the oldest known
      example of gregariousness amongst lobsters and decapods in the fossil record.
      Gregarious behavior in lobsters, also known for extant lobsters, thus developed
      earlier in earth's history than previously known. Moreover, this is one of the
      oldest known examples of decapod crustaceans preserved within cephalopod shells.

PMID- 22412847
TI  - MeCP2 mutation results in compartment-specific reductions in dendritic branching
      and spine density in layer 5 motor cortical neurons of YFP-H mice.
AB  - Rett Syndrome (RTT) is a neurodevelopmental disorder predominantly caused by
      mutations in the X-linked gene MECP2. A primary feature of the syndrome is the
      impaired maturation and maintenance of excitatory synapses in the central nervous
      system (CNS). Different RTT mouse models have shown that particular Mecp2
      mutations have highly variable effects on neuronal architecture. Distinguishing
      MeCP2 mutant cellular phenotypes therefore demands analysis of specific mutations
      in well-defined neuronal subpopulations. We examined a transgenically labeled
      subset of cortical neurons in YFP-H mice crossed with the Mecp2(tm1.1Jae) mutant
      line. YFP(+) Layer 5 pyramidal neurons in the motor cortex of wildtype and
      hemizygous mutant male mice were examined for differences in dendrite morphology
      and spine density. Total basal dendritic length was decreased by 18.6% due to
      both shorter dendrites and reduced branching proximal to the soma. Tangential
      dendrite lengths in the apical tuft were reduced by up to 26.6%. Spine density
      was reduced by 47.4% in the apical tuft and 54.5% in secondary apical dendrites,
      but remained unaffected in primary apical and proximal basal dendrites. We also
      found that MeCP2 mutation reduced the number of YFP(+) cells in YFP-H mice by up
      to 72% in various cortical regions without affecting the intensity of YFP
      expression in individual cells. Our results support the view that the effects of
      MeCP2 mutation are highly context-dependent and cannot be generalized across
      mutation types and cell populations.

PMID- 22412848
TI  - Genetic dissection of the Canq1 locus governing variation in extent of the
      collateral circulation.
AB  - BACKGROUND: Native (pre-existing) collaterals are arteriole-to-arteriole
      anastomoses that interconnect adjacent arterial trees and serve as endogenous
      bypass vessels that limit tissue injury in ischemic stroke, myocardial
      infarction, coronary and peripheral artery disease. Their extent (number and
      diameter) varies widely among mouse strains and healthy humans. We previously
      identified a major quantitative trait locus on chromosome 7 (Canq1, LOD = 29)
      responsible for 37% of the heritable variation in collateral extent between
      C57BL/6 and BALB/c mice. We sought to identify candidate genes in Canq1
      responsible for collateral variation in the cerebral pial circulation, a tissue
      whose strain-dependent variation is shared by similar variation in other tissues.
      METHODS AND FINDINGS: Collateral extent was intermediate in a recombinant inbred
      line that splits Canq1 between the C57BL/6 and BALB/c strains. Phenotyping and
      SNP-mapping of an expanded panel of twenty-one informative inbred strains
      narrowed the Canq1 locus, and genome-wide linkage analysis of a SWRxSJL-F2 cross
      confirmed its haplotype structure. Collateral extent, infarct volume after
      cerebral artery occlusion, bleeding time, and re-bleeding time did not differ in
      knockout mice for two vascular-related genes located in Canq1, IL4ra and Itgal.
      Transcript abundance of 6 out of 116 genes within the 95% confidence interval of
      Canq1 were differentially expressed >2-fold (p-value<0.05/150) in the cortical
      pia mater from C57BL/6 and BALB/c embryos at E14.5, E16.5 and E18.5 time-points
      that span the period of collateral formation. CONCLUSIONS: These findings refine
      the Canq1 locus and identify several genes as high-priority candidates important
      in specifying native collateral formation and its wide variation.

PMID- 22412850
TI  - The Late Jurassic pterosaur Rhamphorhynchus, a frequent victim of the ganoid fish
      Aspidorhynchus?
AB  - Associations of large vertebrates are exceedingly rare in the Late Jurassic
      Solnhofen Limestone of Bavaria, Southern Germany. However, there are five
      specimens of medium-sized pterosaur Rhamphorhynchus that lie adjacent to the
      rostrum of a large individual of the ganoid fish Aspidorhynchus. In one of these,
      a small leptolepidid fish is still sticking in the esophagus of the pterosaur and
      its stomach is full of fish debris. This suggests that the Rhamphorhynchus was
      seized during or immediately after a successful hunt. According to the fossil
      record, Rhamphorhynchus frequently were accidentally seized by large
      Aspidorhnychus. In some cases the fibrous tissue of the wing membrane got
      entangled with the rostral teeth such that the fish was unable to get rid of the
      pterosaur. Such encounters ended fatally for both. Intestinal contents of
      Aspidorhynchus-type fishes are known and mostly comprise fishes and in one single
      case a Homoeosaurus. Obviously Rhamphorhynchus did not belong to the prey
      spectrum of Aspidorhynchus.

PMID- 22412849
TI  - Potentially functional variants of PLCE1 identified by GWASs contribute to
      gastric adenocarcinoma susceptibility in an eastern Chinese population.
AB  - BACKGROUND: Recent genome-wide association studies (GWAS) have found a single
      nucleotide polymorphism (SNP, rs2274223 A>G) in PLCE1 to be associated with risk
      of gastric adenocarcinoma. In the present study, we validated this finding and
      also explored the risk associated with another unreported potentially functional
      SNP (rs11187870 G>C) of PLCE1 in a hospital-based case-control study of 1059
      patients with pathologically confirmed gastric adenocarcinoma and 1240 frequency
      matched healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: We determined genotypes
      of these two SNPs by the Taqman assay and used logistic regression models to
      estimate odds ratios (ORs) and 95% confidence intervals (95% CI). We found that a
      significant higher gastric adenocarcinoma risk was associated with rs2274223
      variant G allele (adjusted OR = 1.35, 95% CI = 1.14-1.60 for AG+GG vs. AA) and
      rs11187870 variant C allele (adjusted OR = 1.26, 95% CI = 1.05-1.50 for CG+CC vs.
      GG). We also found that the number of combined risk alleles (i.e., rs2274223G and
      rs11187870C) was associated with risk of gastric adenocarcinoma in an allele-dose
      effect manner (P(trend) = 0.0002). Stratification analysis indicated that the
      combined effect of rs2274223G and rs11187870C variant alleles was more evident in
      subgroups of males, non-smokers, non-drinkers and patients with gastric cardia
      adenocarcinoma. Further real-time PCR results showed that expression levels of
      PLCE1 mRNA were significantly lower in tumors than in adjacent noncancerous
      tissues (0.019+/-0.002 vs. 0.008+/-0.001, P<0.05). CONCLUSIONS/SIGNIFICANCES: Our
      results further confirmed that genetic variations in PLCE1 may contribute to
      gastric adenocarcinoma risk in an eastern Chinese population.

PMID- 22412851
TI  - Combinatorial complexity and compositional drift in protein interaction networks.
AB  - The assembly of molecular machines and transient signaling complexes does not
      typically occur under circumstances in which the appropriate proteins are
      isolated from all others present in the cell. Rather, assembly must proceed in
      the context of large-scale protein-protein interaction (PPI) networks that are
      characterized both by conflict and combinatorial complexity. Conflict refers to
      the fact that protein interfaces can often bind many different partners in a
      mutually exclusive way, while combinatorial complexity refers to the explosion in
      the number of distinct complexes that can be formed by a network of binding
      possibilities. Using computational models, we explore the consequences of these
      characteristics for the global dynamics of a PPI network based on highly curated
      yeast two-hybrid data. The limited molecular context represented in this data
      type translates formally into an assumption of independent binding sites for each
      protein. The challenge of avoiding the explicit enumeration of the astronomically
      many possibilities for complex formation is met by a rule-based approach to
      kinetic modeling. Despite imposing global biophysical constraints, we find that
      initially identical simulations rapidly diverge in the space of molecular
      possibilities, eventually sampling disjoint sets of large complexes. We refer to
      this phenomenon as "compositional drift". Since interaction data in PPI networks
      lack detailed information about geometric and biological constraints, our study
      does not represent a quantitative description of cellular dynamics. Rather, our
      work brings to light a fundamental problem (the control of compositional drift)
      that must be solved by mechanisms of assembly in the context of large networks.
      In cases where drift is not (or cannot be) completely controlled by the cell,
      this phenomenon could constitute a novel source of phenotypic heterogeneity in
      cell populations.

PMID- 22412852
TI  - First evidence of reproductive adaptation to "island effect" of a dwarf
      Cretaceous Romanian titanosaur, with embryonic integument in ovo.
AB  - BACKGROUND: The Cretaceous vertebrate assemblages of Romania are famous for
      geographically endemic dwarfed dinosaur taxa. We report the first complete egg
      clutches of a dwarf lithostrotian titanosaur, from Totesti, Romania, and its
      reproductive adaptation to the "island effect". METHODOLOGY/FINDINGS: The egg
      clutches were discovered in sequential sedimentary layers of the Maastrichtian
      Sanpetru Formation, Totesti. The occurrence of 11 homogenous clutches in
      successive strata suggests philopatry by the same dinosaur species, which laid
      clutches averaging four ~12 cm diameters eggs. The eggs and eggshells display
      numerous characters shared with the positively identified material from egg
      bearing level 4 of the Auca Mahuevo (Patagonia, Argentina) nemegtosaurid
      lithostrotian nesting site. Microscopic embryonic integument with bacterial
      evidences was recovered in one egg. The millimeter-size embryonic integument
      displays micron size dermal papillae implying an early embryological stage at the
      time of death, likely corresponding to early organogenesis before the skeleton
      formation. CONCLUSIONS/SIGNIFICANCE: The shared oological characters between the
      Hateg specimens and their mainland relatives suggest a highly conservative
      reproductive template, while the nest decrease in egg numbers per clutch may
      reflect an adaptive trait to a smaller body size due to the "island effect". The
      combined presence of the lithostrotian egg and its embryo in the Early Cretaceous
      Gobi coupled with the oological similarities between the Hateg and Auca Mahuevo
      oological material evidence that several titanosaur species migrated from
      Gondwana through the Hateg Island before or during the Aptian/Albian. It also
      suggests that this island might have had episodic land bridges with the rest of
      the European archipelago and Asia deep into the Cretaceous.

PMID- 22412853
TI  - Modeling inhomogeneous DNA replication kinetics.
AB  - In eukaryotic organisms, DNA replication is initiated at a series of chromosomal
      locations called origins, where replication forks are assembled proceeding
      bidirectionally to replicate the genome. The distribution and firing rate of
      these origins, in conjunction with the velocity at which forks progress, dictate
      the program of the replication process. Previous attempts at modeling DNA
      replication in eukaryotes have focused on cases where the firing rate and the
      velocity of replication forks are homogeneous, or uniform, across the genome.
      However, it is now known that there are large variations in origin activity along
      the genome and variations in fork velocities can also take place. Here, we
      generalize previous approaches to modeling replication, to allow for arbitrary
      spatial variation of initiation rates and fork velocities. We derive rate
      equations for left- and right-moving forks and for replication probability over
      time that can be solved numerically to obtain the mean-field replication program.
      This method accurately reproduces the results of DNA replication simulation. We
      also successfully adapted our approach to the inverse problem of fitting
      measurements of DNA replication performed on single DNA molecules. Since such
      measurements are performed on specified portion of the genome, the examined DNA
      molecules may be replicated by forks that originate either within the studied
      molecule or outside of it. This problem was solved by using an effective flux of
      incoming replication forks at the model boundaries to represent the origin
      activity outside the studied region. Using this approach, we show that reliable
      inferences can be made about the replication of specific portions of the genome
      even if the amount of data that can be obtained from single-molecule experiments
      is generally limited.

PMID- 22412854
TI  - The accumulation of organic carbon in mineral soils by afforestation of abandoned
      farmland.
AB  - The afforestation of abandoned farmland significantly influences soil organic
      carbon (OC). However, the dynamics between OC inputs after afforestation and the
      original OC are not well understood. To learn more about soil OC dynamics after
      afforestation of farmland, we measured the soil OC content in paired forest and
      farmland plots in Shaanxi Province, China. The forest plots had been established
      on farmland 18, 24, 48, 100, and 200 yr previously. The natural (13)C abundance
      of soil organic matter was also analyzed to distinguish between crop- and forest
      derived C in the afforested soils. We observed a nonlinear accumulation of total
      OC in the 0-80 cm depth of the mineral soil across time. Total soil OC
      accumulated more rapidly under forest stands aged 18 to 48 yr than under forest
      stands aged 100 or 200 yrs. The rate of OC accumulation was also greater in the 0
      10 cm depth than in the 10-80 cm depth. Forest-derived OC in afforested soils
      also accumulated nonlinearly across time, with the greatest increase in the 0-20
      cm depth. Forest-derived OC in afforest soils accounted for 52-86% of the total
      OC in the 0-10 cm depth, 36-61% of the total OC in the 10-20 cm depth, and 11-50%
      of the total OC in the 20-80 cm depth. Crop-derived OC concentrations in the 0-20
      cm depth decreased slightly after afforestation, but there was no change in crop
      derived OC concentrations in the 20-80 cm depth. The results of our study support
      the claim that afforestation of farmland can sequester atmospheric CO(2) by
      increasing soil OC stocks. Changes in the OC stocks of mineral soils after
      afforestation appear to be influenced mainly by the input of forest-derived C
      rather than by the loss of original OC.

PMID- 22412855
TI  - The axonal guidance receptor neogenin promotes acute inflammation.
AB  - Neuronal guidance proteins (NGP) were originally described in the context of
      axonal growth and migration. Yet recent work has demonstrated that NGPs also
      serve as guidance cues for immune competent cells. A crucial target receptor for
      NGPs during embryonic development is the neogenin receptor, however its role
      during acute inflammation is unknown. We report here that neogenin is abundantly
      expressed outside the nervous system and that animals with endogenous repression
      of neogenin (Neo1(-/-)) demonstrate attenuated changes of acute inflammation.
      Studies using functional inhibition of neogenin resulted in a significant
      attenuation of inflammatory peritonitis. In studies employing bone marrow
      chimeric animals we found the hematopoietic presence of Neo1(-/-) to be
      responsible for the attenuated inflammatory response. Taken together our studies
      suggest that the guidance receptor neogenin holds crucial importance for the
      propagation of an acute inflammatory response and further define mechanisms
      shared between the nervous and the immune system.

PMID- 22412856
TI  - The safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in
      HIV-infected adults on rifampicin-based antitubercular therapy.
AB  - OBJECTIVE: Rifampicin co-administration dramatically reduces plasma lopinavir
      concentrations. Studies in healthy volunteers and HIV-infected patients showed
      that doubling the dose of lopinavir/ritonavir (LPV/r) or adding additional
      ritonavir offsets this interaction. However, high rates of hepatotoxicity were
      observed in healthy volunteers. We evaluated the safety, effectiveness and pre
      dose concentrations of adjusted doses of LPV/r in HIV infected adults treated
      with rifampicin-based tuberculosis treatment. METHODS: Adult patients on a LPV/r
      based antiretroviral regimen and rifampicin-based tuberculosis therapy were
      enrolled. Doubled doses of LPV/r or an additional 300 mg of ritonavir were used
      to overcome the inducing effect of rifampicin. Steady-state lopinavir pre-dose
      concentrations were evaluated every second month. RESULTS: 18 patients were
      enrolled with a total of 79 patient months of observation. 11/18 patients were
      followed up until tuberculosis treatment completion. During tuberculosis
      treatment, the median (IQR) pre-dose lopinavir concentration was 6.8 (1.1-9.2)
      mg/L and 36/47 (77%) were above the recommended trough concentration of 1 mg/L.
      Treatment was generally well tolerated with no grade 3 or 4 toxicity: 8 patients
      developed grade 1 or 2 transaminase elevation, 1 patient defaulted additional
      ritonavir due to nausea and 1 patient developed diarrhea requiring dose
      reduction. Viral loads after tuberculosis treatment were available for 11
      patients and 10 were undetectable. CONCLUSION: Once established on treatment,
      adjusted doses of LPV/r co-administered with rifampicin-based tuberculosis
      treatment were tolerated and LPV pre-dose concentrations were adequate.

PMID- 22412857
TI  - Ethnic variations in the prevalence of diabetic retinopathy in people with
      diabetes attending screening in the United Kingdom (DRIVE UK).
AB  - AIMS: To compare the prevalence of diabetic retinopathy (DR) in people of various
      ethnic groups with diabetes in the United Kingdom (UK). METHODS: The Diabetic
      Retinopathy In Various Ethnic groups in UK (DRIVE UK) Study is a cross-sectional
      study on the ethnic variations of the prevalence of DR and visual impairment in
      two multi-racial cohorts in the UK. People on the diabetes register in West
      Yorkshire and South East London who were screened, treated or monitored between
      April 2008 to July 2009 (London) or August 2009 (West Yorkshire) were included in
      the study. Data included age, sex, ethnic group, type of diabetes, presenting
      visual acuity and the results of grading of diabetic retinopathy. Prevalence
      estimates for the ethnic groups were age-standardised to the white European
      population for comparison purposes. RESULTS: Out of 57,144 people on the two
      diabetic registers, data were available on 50,285 individuals (88.0%), of these
      3,323 had type 1 and 46,962 had type 2 diabetes. In type 2 diabetes, the
      prevalence of any DR was 38.0% (95% confidence interval (CI) 37.4% to 38.5%) in
      white Europeans compared to 52.4% (51.2% to 53.6%) in African/Afro-Caribbeans and
      42.3% (40.3% to 44.2%) in South Asians. Similarly, sight threatening DR was also
      significantly more prevalent in Afro-Caribbeans (11.5%, 95% CI 10.7% to 12.3%)
      and South Asians (10.3%, 9.0% to 11.5%) compared to white Europeans (5.5%, 5.3%
      to 5.8%). Differences observed in Type 1 diabetes did not achieve conventional
      levels of statistical significance, but there were lower numbers for these
      analyses. CONCLUSIONS: Minority ethnic communities with type 2 diabetes in the UK
      are more prone to diabetic retinopathy, including sight-threatening retinopathy
      and maculopathy compared to white Europeans.

PMID- 22412859
TI  - Evolutionary dynamics of fearfulness and boldness: a stochastic simulation model.
AB  - A stochastic simulation model is investigated for the evolution of anti-predator
      behavior in birds. The main goal is to reveal the effects of population size,
      predation threats, and energy lost per escape on the evolutionary dynamics of
      fearfulness and boldness. Two pure strategies, fearfulness and boldness, are
      assumed to have different responses for the predator attacks and nonlethal
      disturbance. On the other hand, the co-existence mechanism of fearfulness and
      boldness is also considered. For the effects of total population size, predation
      threats, and energy lost per escape, our main results show that: (i) the fearful
      (bold) individuals will be favored in a small (large) population, i.e. in a small
      (large) population, the fearfulness (boldness) can be considered to be an ESS;
      (ii) in a population with moderate size, fearfulness would be favored under
      moderate predator attacks; and (iii) although the total population size is the
      most important factor for the evolutionary dynamics of both fearful and bold
      individuals, the small energy lost per escape enables the fearful individuals to
      have the ability to win the advantage even in a relatively large population.
      Finally, we show also that the co-existence of fearful and bold individuals is
      possible when the competitive interactions between individuals are introduced.

PMID- 22412858
TI  - Gibberellin biosynthetic inhibitors make human malaria parasite Plasmodium
      falciparum cells swell and rupture to death.
AB  - Malaria remains as one of the most devastating infectious disease, and continues
      to exact an enormous toll in medical cost and days of labor lost especially in
      the tropics. Effective malaria control and eventual eradication remain a huge
      challenge, with efficacious antimalarials as important intervention/management
      tool. Clearly new alternative drugs that are more affordable and with fewer side
      effects are desirable. After preliminary in vitro assays with plant growth
      regulators and inhibitors, here, we focus on biosynthetic inhibitors of
      gibberellin, a plant hormone with many important roles in plant growth, and show
      their inhibitory effect on the growth of both apicomplexa, Plasmodium falciparum
      and Toxoplasma gondii. Treatment of P. falciparum cultures with the gibberellin
      biosynthetic inhibitors resulted in marked morphological changes that can be
      reversed to a certain degree under hyperosmotic environment. These unique
      observations suggest that changes in the parasite membrane permeability may
      explain the pleiotropic effects observed within the intracellular parasites.

PMID- 22412860
TI  - Genome sequencing and analysis of a type A Clostridium perfringens isolate from a
      case of bovine clostridial abomasitis.
AB  - Clostridium perfringens is a common inhabitant of the avian and mammalian
      gastrointestinal tracts and can behave commensally or pathogenically. Some
      enteric diseases caused by type A C. perfringens, including bovine clostridial
      abomasitis, remain poorly understood. To investigate the potential basis of
      virulence in strains causing this disease, we sequenced the genome of a type A C.
      perfringens isolate (strain F262) from a case of bovine clostridial abomasitis.
      The ~3.34 Mbp chromosome of C. perfringens F262 is predicted to contain 3163
      protein-coding genes, 76 tRNA genes, and an integrated plasmid sequence, Cfrag
      (~18 kb). In addition, sequences of two complete circular plasmids, pF262C (4.8
      kb) and pF262D (9.1 kb), and two incomplete plasmid fragments, pF262A (48.5 kb)
      and pF262B (50.0 kb), were identified. Comparison of the chromosome sequence of
      C. perfringens F262 to complete C. perfringens chromosomes, plasmids and phages
      revealed 261 unique genes. No novel toxin genes related to previously described
      clostridial toxins were identified: 60% of the 261 unique genes were hypothetical
      proteins. There was a two base pair deletion in virS, a gene reported to encode
      the main sensor kinase involved in virulence gene activation. Despite this
      frameshift mutation, C. perfringens F262 expressed perfringolysin O, alpha-toxin
      and the beta2-toxin, suggesting that another regulation system might contribute
      to the pathogenicity of this strain. Two complete plasmids, pF262C (4.8 kb) and
      pF262D (9.1 kb), unique to this strain of C. perfringens were identified.

PMID- 22412861
TI  - Model for glucagon secretion by pancreatic alpha-cells.
AB  - Glucagon hormone is synthesized and released by pancreatic alpha-cells, one of
      the islet-cell types. This hormone, along with insulin, maintains blood glucose
      levels within the physiological range. Glucose stimulates glucagon release at low
      concentrations (hypoglycemia). However, the mechanisms involved in this secretion
      are still not completely clear. Here, using experimental calcium time series
      obtained in mouse pancreatic islets at low and high glucose conditions, we
      propose a glucagon secretion model for alpha-cells. Our model takes into account
      that the resupply of releasable granules is not only controlled by cytoplasmic
      Ca2+, as in other neuroendocrine and endocrine cells, but also by the level of
      extracellular glucose. We found that, although calcium oscillations are highly
      variable, the average secretion rates predicted by the model fall into the range
      of values reported in the literature, for both stimulated and non-stimulated
      conditions. For low glucose levels, the model predicts that there would be a well
      controlled number of releasable granules refilled slowly from a large reserve
      pool, probably to ensure a secretion rate that could last for several minutes.
      Studying the alpha-cell response to the addition of insulin at low glucose, we
      observe that the presence of insulin reduces glucagon release by decreasing the
      islet Ca2+ level. This observation is in line with previous work reporting that
      Ca2+ dynamics, mainly frequency, is altered by insulin. Thus, the present results
      emphasize the main role played by Ca2+ and glucose in the control of glucagon
      secretion by alpha-cells. Our modeling approach also shows that calcium
      oscillations potentiate glucagon secretion as compared to constant levels of this
      cellular messenger. Altogether, the model sheds new light on the subcellular
      mechanisms involved in alpha-cell exocytosis, and provides a quantitative
      predictive tool for studying glucagon secretion modulators in physiological and
      pathological conditions.

PMID- 22412862
TI  - Leber congenital amaurosis associated with AIPL1: challenges in ascribing disease
      causation, clinical findings, and implications for gene therapy.
AB  - Leber Congenital Amaurosis (LCA) and Early Childhood Onset Severe Retinal
      Dystrophy are clinically and genetically heterogeneous retinal disorders
      characterised by visual impairment and nystagmus from birth or early infancy. We
      investigated the prevalence of sequence variants in AIPL1 in a large cohort of
      such patients (n = 392) and probed the likelihood of disease-causation of the
      identified variants, subsequently undertaking a detailed assessment of the
      phenotype of patients with disease-causing mutations. Genomic DNA samples were
      screened for known variants in the AIPL1 gene using a microarray LCA chip, with
      153 of these cases then being directly sequenced. The assessment of disease
      causation of identified AIPL1 variants included segregation testing, assessing
      evolutionary conservation and in silico predictions of pathogenicity. The chip
      identified AIPL1 variants in 12 patients. Sequencing of AIPL1 in 153 patients and
      96 controls found a total of 46 variants, with 29 being novel. In silico analysis
      suggested that only 6 of these variants are likely to be disease-causing,
      indicating a previously unrecognized high degree of polymorphism. Seven patients
      were identified with biallelic changes in AIPL1 likely to be disease-causing. In
      the youngest subject, electroretinography revealed reduced cone photoreceptor
      function, but rod responses were within normal limits, with no measurable ERG in
      other patients. An increasing degree and extent of peripheral retinal
      pigmentation and degree of maculopathy was noted with increasing age in our
      series. AIPL1 is significantly polymorphic in both controls and patients, thereby
      complicating the establishment of disease-causation of identified variants.
      Despite the associated phenotype being characterised by early-onset severe visual
      loss in our patient series, there was some evidence of a degree of retinal
      structural and functional preservation, which was most marked in the youngest
      patient in our cohort. This data suggests that there are patients who have a
      reasonable window of opportunity for gene therapy in childhood.

PMID- 22412863
TI  - Deletion of Porcn in mice leads to multiple developmental defects and models
      human focal dermal hypoplasia (Goltz syndrome).
AB  - BACKGROUND: Focal Dermal Hypoplasia (FDH) is a genetic disorder characterized by
      developmental defects in skin, skeleton and ectodermal appendages. FDH is caused
      by dominant loss-of-function mutations in X-linked PORCN. PORCN orthologues in
      Drosophila and mice encode endoplasmic reticulum proteins required for secretion
      and function of Wnt proteins. Wnt proteins play important roles in embryo
      development, tissue homeostasis and stem cell maintenance. Since features of FDH
      overlap with those seen in mouse Wnt pathway mutants, FDH likely results from
      defective Wnt signaling but molecular mechanisms by which inactivation of PORCN
      affects Wnt signaling and manifestations of FDH remain to be elucidated. RESULTS:
      We introduced intronic loxP sites and a neomycin gene in the mouse Porcn locus
      for conditional inactivation. Porcn-ex3-7flox mice have no apparent developmental
      defects, but chimeric mice retaining the neomycin gene (Porcn-ex3-7Neo-flox) have
      limb, skin, and urogenital abnormalities. Conditional Porcn inactivation by EIIa
      driven or Hprt-driven Cre recombinase results in increased early embryonic
      lethality. Mesenchyme-specific Prx-Cre-driven inactivation of Porcn produces FDH
      like limb defects, while ectodermal Krt14-Cre-driven inactivation produces thin
      skin, alopecia, and abnormal dentition. Furthermore, cell-based assays confirm
      that human PORCN mutations reduce WNT3A secretion. CONCLUSIONS: These data
      indicate that Porcn inactivation in the mouse produces a model for human FDH and
      that phenotypic features result from defective WNT signaling in ectodermal- and
      mesenchymal-derived structures.

PMID- 22412864
TI  - Effects of long-term space flight on erythrocytes and oxidative stress of
      rodents.
AB  - Erythrocyte and hemoglobin losses have been frequently observed in humans during
      space missions; these observations have been designated as "space anemia".
      Erythrocytes exposed to microgravity have a modified rheology and undergo
      hemolysis to a greater extent. Cell membrane composition plays an important role
      in determining erythrocyte resistance to mechanical stress and it is well known
      that membrane composition might be influenced by external events, such as
      hypothermia, hypoxia or gravitational strength variations. Moreover, an altered
      cell membrane composition, in particular in fatty acids, can cause a greater
      sensitivity to peroxidative stress, with increase in membrane fragility. Solar
      radiation or low wavelength electromagnetic radiations (such as gamma rays) from
      the Earth or the space environment can split water to generate the hydroxyl
      radical, very reactive at the site of its formation, which can initiate chain
      reactions leading to lipid peroxidation. These reactive free radicals can react
      with the non-radical molecules, leading to oxidative damage of lipids, proteins
      and DNA, etiologically associated with various diseases and morbidities such as
      cancer, cell degeneration, and inflammation. Indeed, radiation constitutes on of
      the most important hazard for humans during long-term space flights. With this
      background, we participated to the MDS tissue-sharing program performing analyses
      on mice erythrocytes flown on the ISS from August to November 2009. Our results
      indicate that space flight induced modifications in cell membrane composition and
      increase of lipid peroxidation products, in mouse erythrocytes. Moreover,
      antioxidant defenses in the flight erythrocytes were induced, with a significant
      increase of glutathione content as compared to both vivarium and ground control
      erythrocytes. Nonetheless, this induction was not sufficient to prevent damages
      caused by oxidative stress. Future experiments should provide information helpful
      to reduce the effects of oxidative stress exposure and space anemia, possibly by
      integrating appropriate dietary elements and natural compounds that could act as
      antioxidants.

PMID- 22412865
TI  - The role of age and exposure to Plasmodium falciparum in the rate of acquisition
      of naturally acquired immunity: a randomized controlled trial.
AB  - BACKGROUND: The rate of acquisition of naturally acquired immunity (NAI) against
      malaria predominantly depends on transmission intensity and age, although
      disentangling the effects of these is difficult. We used chemoprophylaxis to
      selectively control exposure to P. falciparum during different periods in infancy
      and explore the effect of age in the build-up of NAI, measured as risk of
      clinical malaria. METHODS AND FINDINGS: A three-arm double-blind randomized
      placebo-controlled trial was conducted in 349 infants born to Mozambican HIV
      negative women. The late exposure group (LEG) received monthly Sulfadoxine
      Pyrimethamine (SP) plus Artesunate (AS) from 2.5-4.5 months of age and monthly
      placebo from 5.5-9.5 months; the early exposure group (EEG) received placebo from
      2.5-4.5 months and SP+AS from 5.5-9.5 months; and the control group (CG) received
      placebo from 2.5-9.5 months. Active and passive case detection (PCD) were
      conducted from birth to 10.5 and 24 months respectively. The primary endpoint was
      time to first or only episode of malaria in the second year detected by PCD. The
      incidence of malaria during the second year was of 0.50, 0.51 and 0.35
      episodes/PYAR in the LEG, EEG and CG respectively (p = 0.379 for the adjusted
      comparison of the 3 groups). The hazard ratio of the adjusted comparison between
      the LEG and the CG was 1.38 (0.83-2.28, p = 0.642) and that between the EEG and
      the CG was 1.35 (0.81-2.24, p = 0.743). CONCLUSIONS: After considerably
      interfering with exposure during the first year of life, there was a trend
      towards a higher risk of malaria in the second year in children who had received
      chemoprophylaxis, but there was no significant rebound. No evidence was found
      that the age of first exposure to malaria affects the rate of acquisition of NAI.
      Thus, the timing of administration of antimalarial interventions like malaria
      vaccines during infancy does not appear to be a critical determinant. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00231452.

PMID- 22412866
TI  - Signatures of T cells as correlates of immunity to Francisella tularensis.
AB  - Tularemia or vaccination with the live vaccine strain (LVS) of Francisella
      tularensis confers long-lived cell-mediated immunity. We hypothesized that this
      immunity depends on polyfunctional memory T cells, i.e., CD4(+) and/or CD8(+) T
      cells with the capability to simultaneously express several functional markers.
      Multiparametric flow cytometry, measurement of secreted cytokines, and analysis
      of lymphocyte proliferation were used to characterize in vitro recall responses
      of peripheral blood mononuclear cells (PBMC) to killed F. tularensis antigens
      from the LVS or Schu S4 strains. PBMC responses were compared between individuals
      who had contracted tularemia, had been vaccinated, or had not been exposed to F.
      tularensis (naive). Significant differences were detected between either of the
      immune donor groups and naive individuals for secreted levels of IL-5, IL-6, IL
      10, IL-12, IL-13, IFN-gamma, MCP-1, and MIP-1beta. Expression of IFN-gamma, MIP
      1beta, and CD107a by CD4(+)CD45RO(+) or CD8(+)CD45RO(+) T cells correlated to
      antigen concentrations. In particular, IFN-gamma and MIP-1beta strongly
      discriminated between immune and naive individuals. Only one cytokine, IL-6,
      discriminated between the two groups of immune individuals. Notably, IL-2- or TNF
      alpha-secretion was low. Our results identify functional signatures of T cells
      that may serve as correlates of immunity and protection against F. tularensis.

PMID- 22412868
TI  - Fast negative feedback enables mammalian auditory nerve fibers to encode a wide
      dynamic range of sound intensities.
AB  - Mammalian auditory nerve fibers (ANF) are remarkable for being able to encode a
      40 dB, or hundred fold, range of sound pressure levels into their firing rate.
      Most of the fibers are very sensitive and raise their quiescent spike rate by a
      small amount for a faint sound at auditory threshold. Then as the sound intensity
      is increased, they slowly increase their spike rate, with some fibers going up as
      high as ~300 Hz. In this way mammals are able to combine sensitivity and wide
      dynamic range. They are also able to discern sounds embedded within background
      noise. ANF receive efferent feedback, which suggests that the fibers are
      readjusted according to the background noise in order to maximize the information
      content of their auditory spike trains. Inner hair cells activate currents in the
      unmyelinated distal dendrites of ANF where sound intensity is rate-coded into
      action potentials. We model this spike generator compartment as an attenuator
      that employs fast negative feedback. Input current induces rapid and proportional
      leak currents. This way ANF are able to have a linear frequency to input current
      (f-I) curve that has a wide dynamic range. The ANF spike generator remains very
      sensitive to threshold currents, but efferent feedback is able to lower its gain
      in response to noise.

PMID- 22412869
TI  - Quorum decision-making in foraging fish shoals.
AB  - Quorum responses provide a means for group-living animals to integrate and filter
      disparate social information to produce accurate and coherent group decisions. A
      quorum response may be defined as a steep increase in the probability of group
      members performing a given behaviour once a threshold minimum number of their
      group mates already performing that behaviour is exceeded. In a previous study we
      reported the use of a quorum response in group decision-making of threespine
      sticklebacks (Gasterosteus aculeatus) under a simulated predation threat. Here we
      examine the use of quorum responses by shoals of sticklebacks in first locating
      and then leaving a foraging patch. We show that a quorum rule explains movement
      decisions by threespine sticklebacks toward and then away from a food patch.
      Following both to and from a food patch occurred when a threshold number of
      initiators was exceeded, with the threshold being determined by the group size.

PMID- 22412867
TI  - Differences in HIV natural history among African and non-African seroconverters
      in Europe and seroconverters in sub-Saharan Africa.
AB  - INTRODUCTION: It is unknown whether HIV treatment guidelines, based on resource
      rich country cohorts, are applicable to African populations. METHODS: We
      estimated CD4 cell loss in ART-naive, AIDS-free individuals using mixed models
      allowing for random intercept and slope, and time from seroconversion to clinical
      AIDS, death and antiretroviral therapy (ART) initiation by survival methods.
      Using CASCADE data from 20 European and 3 sub-Saharan African (SSA) cohorts of
      heterosexually-infected individuals, aged >=15 years, infected >=2000, we
      compared estimates between non-African Europeans, Africans in Europe, and
      Africans in SSA. RESULTS: Of 1,959 (913 non-Africans, 302 Europeans-African
      origin, 744 SSA), two-thirds were female; median age at seroconversion was 31
      years. Individuals in SSA progressed faster to clinical AIDS but not to death or
      non-TB AIDS. They also initiated ART later than Europeans and at lower CD4 cell
      counts. In adjusted models, Africans (especially from Europe) had lower CD4
      counts at seroconversion and slower CD4 decline than non-African Europeans.
      Median (95% CI) CD4 count at seroconversion for a 15-29 year old woman was 607
      (588-627) (non-African European), 469 (442-497) (European-African origin) and 570
      (551-589) (SSA) cells/uL with respective CD4 decline during the first 4 years of
      259 (228-289), 155 (110-200), and 199 (174-224) cells/uL (p<0.01). DISCUSSION:
      Despite differences in CD4 cell count evolution, death and non-TB AIDS rates were
      similar across study groups. It is therefore prudent to apply current ART
      guidelines from resource-rich countries to African populations.

PMID- 22412870
TI  - A metalloproteinase secreted by Streptococcus pneumoniae removes membrane mucin
      MUC16 from the epithelial glycocalyx barrier.
AB  - The majority of bacterial infections occur across wet-surfaced mucosal epithelia,
      including those that cover the eye, respiratory tract, gastrointestinal tract and
      genitourinary tract. The apical surface of all these mucosal epithelia is covered
      by a heavily glycosylated glycocalyx, a major component of which are membrane
      associated mucins (MAMs). MAMs form a barrier that serves as one of the first
      lines of defense against invading bacteria. While opportunistic bacteria rely on
      pre-existing defects or wounds to gain entry to epithelia, non opportunistic
      bacteria, especially the epidemic disease-causing ones, gain access to epithelial
      cells without evidence of predisposing injury. The molecular mechanisms employed
      by these non opportunistic pathogens to breach the MAM barrier remain unknown. To
      test the hypothesis that disease-causing non opportunistic bacteria gain access
      to the epithelium by removal of MAMs, corneal, conjunctival, and tracheobronchial
      epithelial cells, cultured to differentiate to express the MAMs, MUCs 1, 4, and
      16, were exposed to a non encapsulated, non typeable strain of Streptococcus
      pneumoniae (SP168), which causes epidemic conjunctivitis. The ability of strain
      SP168 to induce MAM ectodomain release from epithelia was compared to that of
      other strains of S. pneumoniae, as well as the opportunistic pathogen
      Staphylococcus aureus. The experiments reported herein demonstrate that the
      epidemic disease-causing S. pneumoniae species secretes a metalloproteinase,
      ZmpC, which selectively induces ectodomain shedding of the MAM MUC16.
      Furthermore, ZmpC-induced removal of MUC16 from the epithelium leads to loss of
      the glycocalyx barrier function and enhanced internalization of the bacterium.
      These data suggest that removal of MAMs by bacterial enzymes may be an important
      virulence mechanism employed by disease-causing non opportunistic bacteria to
      gain access to epithelial cells to cause infection.

PMID- 22412871
TI  - Embryonic stem cell-derived factors inhibit T effector activation and induce T
      regulatory cells by suppressing PKC-theta activation.
AB  - Embryonic stem cells (ESCs) possess immune privileged properties and have the
      capacity to modulate immune activation. However, the mechanisms by which ESCs
      inhibit immune activation remain mostly unknown. We have previously shown that
      ESC-derived factors block dendritic cell maturation, thereby indirectly affecting
      T cell activation. Here, we show that ESC-derived factors also directly affect T
      cell activation. We provide the first demonstration that ESC-derived factors
      significantly down-regulated the expressions of IL-2 and IFN-gamma, while
      markedly up-regulating the expression of IL-10, TGF-beta, and Treg transcription
      factor Foxp3 in CD4+ CD25+ T cells. Furthermore, ESC-derived factors robustly
      suppressed T cell proliferation in response to the protein kinase C-theta (PKC
      theta) activator phorbol 12-myristate 13-acetate (PMA). Western blot analysis
      indicated that ESC-derived factors prevented PKC-theta phosphorylation without
      influencing total PKC-theta levels. Moreover, IkappaB-alpha degradation was
      abrogated, confirming absence of PKC-theta activity. The impact of ESC-derived
      factors on PKC-theta activation appeared to be specific since other upstream T
      cell signaling components were not affected. In conclusion, ESCs appear to
      directly impact T cell activation and polarization by negatively regulating the
      PKC-theta pathway.

PMID- 22412872
TI  - Identification of DreI as an antiviral factor regulated by RLR signaling pathway.
AB  - BACKGROUND: Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) had been
      demonstrated to prime interferon (IFN) response against viral infection via the
      conserved RLR signaling in fish, and a novel fish-specific gene, the grass carp
      reovirus (GCRV)-induced gene 2 (Gig2), had been suggested to play important role
      in host antiviral response. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we
      cloned and characterized zebrafish Gig2 homolog (named Danio rerio Gig2-I, DreI),
      and revealed its antiviral role and expressional regulation signaling pathway. RT
      PCR, Western blot and promoter activity assay indicate that DreI can be induced
      by poly I:C, spring viremia of carp virus (SVCV) and recombinant IFN (rIFN),
      showing that DreI is a typical ISG. Using the pivotal signaling molecules of RLR
      pathway, including RIG-I, MDA5 and IRF3 from crucian carp, it is found that DreI
      expression is regulated by RLR cascade and IRF3 plays an important role in this
      regulation. Furthermore, promoter mutation assay confirms that the IFN-stimulated
      regulatory elements (ISRE) in the 5' flanking region of DreI is essential for its
      induction. Finally, overexpression of DreI leads to establish a strong antiviral
      state against SVCV and Rana grylio virus (RGV) infection in EPC (Epithelioma
      papulosum cyprinid) cells. CONCLUSIONS/SIGNIFICANCE: These data indicate that
      DreI is an antiviral protein, which is regulated by RLR signaling pathway.

PMID- 22412873
TI  - The tempered polymerization of human neuroserpin.
AB  - Neuroserpin, a member of the serpin protein superfamily, is an inhibitor of
      proteolytic activity that is involved in pathologies such as ischemia,
      Alzheimer's disease, and Familial Encephalopathy with Neuroserpin Inclusion
      Bodies (FENIB). The latter belongs to a class of conformational diseases, known
      as serpinopathies, which are related to the aberrant polymerization of serpin
      mutants. Neuroserpin is known to polymerize, even in its wild type form, under
      thermal stress. Here, we study the mechanism of neuroserpin polymerization over a
      wide range of temperatures by different techniques. Our experiments show how the
      onset of polymerization is dependent on the formation of an intermediate
      monomeric conformer, which then associates with a native monomer to yield a
      dimeric species. After the formation of small polymers, the aggregation proceeds
      via monomer addition as well as polymer-polymer association. No further secondary
      mechanism takes place up to very high temperatures, thus resulting in the
      formation of neuroserpin linear polymeric chains. Most interesting, the overall
      aggregation is tuned by the co-occurrence of monomer inactivation (i.e. the
      formation of latent neuroserpin) and by a mechanism of fragmentation. The
      polymerization kinetics exhibit a unique modulation of the average mass and size
      of polymers, which might suggest synchronization among the different processes
      involved. Thus, fragmentation would control and temper the aggregation process,
      instead of enhancing it, as typically observed (e.g.) for amyloid fibrillation.

PMID- 22412874
TI  - Comparative skull morphology of uropeltid snakes (Alethinophidia: Uropeltidae)
      with special reference to disarticulated elements and variation.
AB  - Uropeltids form a diverse clade of highly derived, fossorial snakes that, because
      of their phylogenetic position among other alethinophidian lineages, may play a
      key role in understanding the early evolution of cranial morphology in snakes. We
      include detailed osteological descriptions of crania and mandibles for eight
      uropeltid species from three nominal genera (Uropeltis, Rhinophis, and
      Brachyophidium) and emphasize disarticulated elements and the impact of
      intraspecific variation on previously proposed morphological characters used for
      phylogenetic analysis. Preliminary analysis of phylogenetic relationships
      strongly supports a clade composed exclusively of species of Plectrurus,
      Uropeltis, and Rhinophis. However, monophyly of each of those genera and
      Melanophidium is not upheld. There is moderate support that Sri Lankan species
      (e.g., Rhinophis and Uropeltis melanogaster) are monophyletic with respect to
      Indian uropeltids. Previously proposed characters that are phylogenetically
      informative include the shape of the nasals, length of the occipital condyle,
      level of development of the posteroventral process of the dentary, and
      participation of the parietal in the optic foramen. Additionally, thirty new
      features that may be systematically informative are identified and described, but
      were not verified for their utility. Such verification must await availability of
      additional disarticulated cranial material from a larger sample of taxa. All
      characters require further testing through increased focus on sources and
      patterns of intraspecific variation, inclusion of broader taxonomic samples in
      comparative studies, and exploration of skeletal development, sexual dimorphism,
      and biogeographic patterns. Additionally, trends in the relative enlargement of
      the sensory capsules, reduction in cranial ossification and dentition, fusion of
      elements, and the appearance of novel morphological conditions, such as the
      structure and location of the suspensorium, may be related to fossoriality and
      miniaturization in some uropeltid taxa, and may complicate analysis of
      relationships within Uropeltidae and among alethinophidian snakes.

PMID- 22412875
TI  - Bone marrow transplantation restores follicular maturation and steroid hormones
      production in a mouse model for primary ovarian failure.
AB  - Recent studies suggest that bone marrow stem cells (BMSCs) are promising grafts
      to treat a variety of diseases, including reproductive dysfunction. Primary
      ovarian failure is characterized by amenorrhea and infertility in a normal
      karyotype female, with an elevated serum level of follicle-stimulating hormone
      (FSH) and a decrease level of estrogen caused by a mutation in FSH receptor
      (FSHR) gene. Currently, there is no effective treatment for this condition. The
      phenotype of FSHR (-/-) mouse, FORKO (follitropin receptor knockout), is a
      suitable model to study ovarian failure in humans. Female FORKO mice have
      elevated FSH, decreased estrogen levels, are sterile because of the absence of
      folliculogenesis, and display thin uteri and small nonfunctional ovaries. In this
      study, we determined the effects of BMSC transplantation on reproductive
      physiology in this animal model. Twenty four hours post BMSC transplantation,
      treated animals showed detectable estroidogeneic changes in daily vaginal smear.
      Significant increase in total body weight and reproductive organs was observed in
      treated animals. Hemotoxylin and eosin (H&E) evaluation of the ovaries
      demonstrated significant increase in both the maturation and the total number of
      the follicles in treated animals. The FSH dropped to 40-50% and estrogen
      increased 4-5.5 times in the serum of treated animals compared to controls. The
      FSHR mRNA was detected in the ovaries of treated animals. Our results show that
      intravenously injected BMSCs were able to reach the ovaries of FORKO mice,
      differentiate and express FHSR gene, make FSHR responsive to FSH, resume estrogen
      hormone production, and restore folliculogenesis.

PMID- 22412876
TI  - Resting and post bronchial challenge testing carbon dioxide partial pressure in
      individuals with and without asthma.
AB  - OBJECTIVE: There is conflicting evidence about resting carbon dioxide levels in
      asthmatic individuals. We wanted to determine if transcutaneously measured carbon
      dioxide levels prior and during bronchial provocation testing differ according to
      asthma status reflecting dysfunctional breathing. METHODS: We investigated active
      firefighters and policemen by means of a validated questionnaire on respiratory
      symptoms, spirometry, bronchial challenge testing with methacholine (MCT) and
      measurement of transcutaneous blood carbon dioxide partial pressure (PtcCO(2)) at
      rest prior performing spirometry, one minute and five minutes after termination
      of MCT. A respiratory physician blinded to the PtcCO(2) results assigned a
      diagnosis of asthma after reviewing the available study data and the files of the
      workers medical screening program. RESULTS: The study sample consisted of 128
      male and 10 female individuals. Fifteen individuals (11%) had physician-diagnosed
      asthma. There was no clinically important difference in median PtcCO(2) at rest,
      one and five minutes after recovery from MCT in asthmatics compared to non
      asthmatics (35.6 vs 35.7 mmHg, p = 0.466; 34.7 vs 33.4 mmHg, p = 0.245 and 37.4
      vs 36.4 mmHg, p = 0.732). The median drop in PtcCO(2) during MCT and the increase
      after MCT was lower in asthmatics compared to non-asthmatics (0.1 vs 3.2 mmHg, p
      = 0.014 and 1.9 vs 2.9 mmHg, p = 0.025). CONCLUSIONS: PtcCO(2) levels at rest
      prior and during recovery after MCT do not differ in individuals with or without
      physician diagnosed asthma. The fall and subsequent increase in PtcCO(2) levels
      are higher in non-asthmatics than in asthmatics and seems to be related with
      increased number of respiratory maneuvers during MCT.

PMID- 22412877
TI  - OneG: a computational tool for predicting cryptic intermediates in the unfolding
      kinetics of proteins under native conditions.
AB  - Understanding the relationships between conformations of proteins and their
      stabilities is one key to address the protein folding paradigm. The free energy
      change (DeltaG) of unfolding reactions of proteins is measured by traditional
      denaturation methods and native hydrogen-deuterium (H/D) exchange methods.
      However, the free energy of unfolding (DeltaG(U)) and the free energy of exchange
      (DeltaG(HX)) of proteins are not in good agreement, though the experimental
      conditions of both methods are well matching to each other. The anomaly is due to
      any one or combinations of the following reasons: (i) effects of cis-trans
      proline isomerisation under equilibrium unfolding reactions of proteins (ii)
      inappropriateness in accounting the baselines of melting curves (iii) presence of
      cryptic intermediates, which may elude the melting curve analysis and (iv)
      existence of higher energy metastable states in the H/D exchange reactions of
      proteins. Herein, we have developed a novel computational tool, OneG, which
      accounts the discrepancy between DeltaG(U) and DeltaG(HX) of proteins by
      systematically accounting all the four factors mentioned above. The program is
      fully automated and requires four inputs: three-dimensional structures of
      proteins, DeltaG(U), DeltaG(U)(*) and residue-specific DeltaG(HX) determined
      under EX2-exchange conditions in the absence of denaturants. The robustness of
      the program has been validated using experimental data available for proteins
      such as cytochrome c and apocytochrome b(562) and the data analyses revealed that
      cryptic intermediates of the proteins detected by the experimental methods and
      the cryptic intermediates predicted by the OneG for those proteins were in good
      agreement. Furthermore, using OneG, we have shown possible existence of cryptic
      intermediates and metastable states in the unfolding pathways of cardiotoxin III
      and cobrotoxin, respectively, which are homologous proteins. The unique
      application of the program to map the unfolding pathways of proteins under native
      conditions have been brought into fore and the program is publicly available at
      http://sblab.sastra.edu/oneg.html.

PMID- 22412878
TI  - Transcriptomics comparison between porcine adipose and bone marrow mesenchymal
      stem cells during in vitro osteogenic and adipogenic differentiation.
AB  - Bone-marrow mesenchymal stem cells (BMSC) are considered the gold standard for
      use in tissue regeneration among mesenchymal stem cells (MSC). The abundance and
      ease of harvest make the adipose-derived stem cells (ASC) an attractive
      alternative to BMSC. The aim of the present study was to compare the
      transcriptome of ASC and BMSC, respectively isolated from subcutaneous adipose
      tissue and femur of 3 adult pigs, during in vitro osteogenic and adipogenic
      differentiation for up to four weeks. At 0, 2, 7, and 21 days of differentiation
      RNA was extracted for microarray analysis. A False Discovery Rate <=0.05 for
      overall interactions effect and P<0.001 between comparisons were used to
      determine differentially expressed genes (DEG). Ingenuity Pathway Analysis and
      DAVID performed the functional analysis of the DEG. Functional analysis of
      highest expressed genes in MSC and genes more expressed in MSC vs. fully
      differentiated tissues indicated low immunity and high angiogenic capacity. Only
      64 genes were differentially expressed between ASC and BMSC before
      differentiation. The functional analysis uncovered a potential larger angiogenic,
      osteogenic, migration, and neurogenic capacity in BMSC and myogenic capacity in
      ASC. Less than 200 DEG were uncovered between ASC and BMSC during
      differentiation. Functional analysis also revealed an overall greater lipid
      metabolism in ASC, while BMSC had a greater cell growth and proliferation. The
      time course transcriptomic comparison between differentiation types uncovered
      <500 DEG necessary to determine cell fate. The functional analysis indicated that
      osteogenesis had a larger cell proliferation and cytoskeleton organization with a
      crucial role of G-proteins. Adipogenesis was driven by PPAR signaling and had
      greater angiogenesis, lipid metabolism, migration, and tumorigenesis capacity.
      Overall the data indicated that the transcriptome of the two MSC is relatively
      similar across the conditions studied. In addition, functional analysis data
      might indicate differences in therapeutic application.

PMID- 22412879
TI  - Impartial third-party interventions in captive chimpanzees: a reflection of
      community concern.
AB  - Because conflicts among social group members are inevitable, their management is
      crucial for group stability. The rarest and most interesting form of conflict
      management is policing, i.e., impartial interventions by bystanders, which is of
      considerable interest due to its potentially moral nature. Here, we provide
      descriptive and quantitative data on policing in captive chimpanzees. First, we
      report on a high rate of policing in one captive group characterized by recently
      introduced females and a rank reversal between two males. We explored the
      influence of various factors on the occurrence of policing. The results show that
      only the alpha and beta males acted as arbitrators using manifold tactics to
      control conflicts, and that their interventions strongly depended on conflict
      complexity. Secondly, we compared the policing patterns in three other captive
      chimpanzee groups. We found that although rare, policing was more prevalent at
      times of increased social instability, both high-ranking males and females
      performed policing, and conflicts of all sex-dyad combinations were policed.
      These results suggest that the primary function of policing is to increase group
      stability. It may thus reflect prosocial behaviour based upon "community
      concern." However, policing remains a rare behaviour and more data are needed to
      test the generality of this hypothesis.

PMID- 22412880
TI  - MHO1, an evolutionarily conserved gene, is synthetic lethal with PLC1; Mho1p has
      a role in invasive growth.
AB  - The novel protein Memo (Mediator of ErbB2 driven cell motility) was identified in
      a screen for ErbB2 interacting proteins and found to have an essential function
      in cell motility. Memo is evolutionarily conserved with homologs found in all
      branches of life; the human and yeast proteins have a similarity of >50%. In the
      present study we used the model organism S. cerevisiae to characterize the Memo
      homologue Mho1 (Yjr008wp) and to investigate its function in yeast. In a
      synthetic lethal screen we found MHO1 as a novel synthetic lethal partner of
      PLC1, which encodes the single phospholipase C in yeast. Double-deleted cells
      lacking MHO1 and PLC1, proliferate for up to ten generations. Introduction of
      human Memo into the memoDeltaplc1Delta strain rescued the synthetic lethal
      phenotype suggesting that yeast and human proteins have similar functions. Mho1
      is present in the cytoplasm and the nucleus of yeast cells; the same distribution
      of Memo was found in mammalian cells. None of the Memo homologues have a
      characteristic nuclear localization sequence, however, a conserved nuclear export
      sequence is found in all. In mammalian cells, blocking nuclear export with
      Leptomycin B led to nuclear Memo accumulation, suggesting that it is actively
      exported from the nucleus. In yeast MHO1 expression is induced by stress
      conditions. Since invasive growth in S. cerevisiea is also stress-induced, we
      tested Mho1's role in this response. MHO1 deletion had no effect on invasion
      induced by nutrient deprivation, however, Mho1 overexpression blocked the
      invasive ability of yeast cells, suggesting that Mho1 might be acting in a
      dominant negative manner. Taken together, our results show that MHO1 is a novel
      synthetic lethal interactor with PLC1, and that both gene products are required
      for proliferation. Moreover, a role for Memo in cell motility/invasion appears to
      be conserved across species.

PMID- 22412881
TI  - Risk for hospital readmission following bariatric surgery.
AB  - BACKGROUND AND OBJECTIVES: Complications resulting in hospital readmission are
      important concerns for those considering bariatric surgery, yet present
      understanding of the risk for these events is limited to a small number of
      patient factors. We sought to identify demographic characteristics, concomitant
      morbidities, and perioperative factors associated with hospital readmission
      following bariatric surgery. METHODS: We report on a prospective observational
      study of 24,662 patients undergoing primary RYGB and 26,002 patients undergoing
      primary AGB at 249 and 317 Bariatric Surgery Centers of Excellence (BSCOE),
      respectively, in the United States from January 2007 to August 2009. Data were
      collected using standardized assessments of demographic factors and
      comorbidities, as well as longitudinal records of hospital readmissions,
      complications, and mortality. RESULTS: The readmission rate was 5.8% for RYGB and
      1.2% for AGB patients 30 days after discharge. The greatest predictors for
      readmission following RYGB were prolonged length of stay (adjusted odds ratio
      [OR], 2.3; 95% confidence interval [CI], 2.0-2.7), open surgery (OR, 1.8; CI, 1.4
      2.2), and pseudotumor cerebri (OR, 1.6; CI, 1.1-2.4). Prolonged length of stay
      (OR, 2.3; CI, 1.6-3.3), history of deep venous thrombosis or pulmonary embolism
      (OR, 2.1; CI, 1.3-3.3), asthma (OR, 1.5; CI, 1.1-2.1), and obstructive sleep
      apnea (OR, 1.5; CI, 1.1-1.9) were associated with the greatest increases in
      readmission risk for AGB. The 30-day mortality rate was 0.14% for RYGB and 0.02%
      for AGB. CONCLUSION: Readmission rates are low and mortality is very rare
      following bariatric surgery, but risk for both is significantly higher after
      RYGB. Predictors of readmission were disparate for the two procedures. Results do
      not support excluding patients with certain comorbidities since any reductions in
      overall readmission rates would be very small on the absolute risk scale. Future
      research should evaluate the efficacy of post-surgical managed care plans for
      patients at higher risk for readmission and adverse events.

PMID- 22412882
TI  - Reduced serotonin reuptake transporter (SERT) function causes insulin resistance
      and hepatic steatosis independent of food intake.
AB  - Serotonin reuptake transporter (SERT) is a key regulator of serotonin
      neurotransmission and a major target of antidepressants. Antidepressants, such as
      selectively serotonin reuptake inhibitors (SSRIs), that block SERT function are
      known to affect food intake and body weight. Here, we provide genetic evidence
      that food intake and metabolism are regulated by separable mechanisms of SERT
      function. SERT-deficient mice ate less during both normal diet and high fat diet
      feeding. The reduced food intake was accompanied with markedly elevated plasma
      leptin levels. Despite reduced food intake, SERT-deficient mice exhibited glucose
      intolerance and insulin resistance, and progressively developed obesity and
      hepatic steatosis. Several lines of evidence indicate that the metabolic deficits
      of SERT-deficient mice are attributable to reduced insulin-sensitivity in
      peripheral tissues. First, SERT-deficient mice exhibited beta-cell hyperplasia
      and islet-mass expansion. Second, biochemical analyses revealed constitutively
      elevated JNK activity and diminished insulin-induced AKT activation in the liver
      of SERT-deficient mice. SERT-deficient mice exhibited hyper-JNK activity and
      hyperinsulinemia prior to the development of obesity. Third, enhancing AKT
      signaling by PTEN deficiency corrected glucose tolerance in SERT-deficient mice.
      These findings have potential implications for designing selective SERT drugs for
      weight control and the treatment of metabolic syndromes.

PMID- 22412883
TI  - Aronia melanocarpa juice induces a redox-sensitive p73-related caspase 3
      dependent apoptosis in human leukemia cells.
AB  - Polyphenols are natural compounds widely present in fruits and vegetables, which
      have antimutagenic and anticancer properties. The aim of the present study was to
      determine the anticancer effect of a polyphenol-rich Aronia melanocarpa juice
      (AMJ) containing 7.15 g/L of polyphenols in the acute lymphoblastic leukemia
      Jurkat cell line, and, if so, to clarify the underlying mechanism and to identify
      the active polyphenols involved. AMJ inhibited cell proliferation, which was
      associated with cell cycle arrest in G(2)/M phase, and caused the induction of
      apoptosis. These effects were associated with an upregulation of the expression
      of tumor suppressor p73 and active caspase 3, and a downregulation of the
      expression of cyclin B1 and the epigenetic integrator UHRF1. AMJ significantly
      increased the formation of reactive oxygen species (ROS), decreased the
      mitochondrial membrane potential and caused the release of cytochrome c into the
      cytoplasm. Treatment with intracellular ROS scavengers prevented the AMJ-induced
      apoptosis and upregulation of the expression of p73 and active caspase 3. The
      fractionation of the AMJ and the use of identified isolated compounds indicated
      that the anticancer activity was associated predominantly with chlorogenic acids,
      some cyanidin glycosides, and derivatives of quercetin. AMJ treatment also
      induced apoptosis of different human lymphoblastic leukemia cells (HSB-2, Molt-4
      and CCRF-CEM). In addition, AMJ exerted a strong pro-apoptotic effect in human
      primary lymphoblastic leukemia cells but not in human normal primary T
      lymphocytes. Thus, the present findings indicate that AMJ exhibits strong
      anticancer activity through a redox-sensitive mechanism in the p53-deficient
      Jurkat cells and that this effect involves several types of polyphenols. They
      further suggest that AMJ has chemotherapeutic properties against acute
      lymphoblastic leukemia by selectively targeting lymphoblast-derived tumor cells.

PMID- 22412884
TI  - Economic evaluation of first-line treatments for metastatic renal cell carcinoma:
      a cost-effectiveness analysis in a health resource-limited setting.
AB  - BACKGROUND: To estimate, from the perspective of the Chinese healthcare system,
      the economic outcomes of five different first-line strategies among patients with
      metastatic renal cell carcinoma (mRCC). METHODS AND FINDINGS: A decision-analytic
      model was developed to simulate the lifetime disease course associated with renal
      cell carcinoma. The health and economic outcomes of five first-line strategies
      (interferon-alfa, interleukin-2, interleukin-2 plus interferon-alfa, sunitinib
      and bevacizumab plus interferon-alfa) were estimated and assessed by indirect
      comparison. The clinical and utility data were taken from published studies. The
      cost data were estimated from local charge data and current Chinese practices.
      Sensitivity analyses were used to explore the impact of uncertainty regarding the
      results. The impact of the sunitinib patient assistant program (SPAP) was
      evaluated via scenario analysis. The base-case analysis showed that the sunitinib
      strategy yielded the maximum health benefits: 2.71 life years and 1.40 quality
      adjusted life-years (QALY). The marginal cost-effectiveness (cost per additional
      QALY) gained via the sunitinib strategy compared with the conventional strategy
      was $220,384 (without SPAP, interleukin-2 plus interferon-alfa and bevacizumab
      plus interferon-alfa were dominated) and $16,993 (with SPAP, interferon-alfa,
      interleukin-2 plus interferon-alfa and bevacizumab plus interferon-alfa were
      dominated). In general, the results were sensitive to the hazard ratio of
      progression-free survival. The probabilistic sensitivity analysis demonstrated
      that the sunitinib strategy with SPAP was the most cost-effective approach when
      the willingness-to-pay threshold was over $16,000. CONCLUSIONS: Our analysis
      suggests that traditional cytokine therapy is the cost-effective option in the
      Chinese healthcare setting. In some relatively developed regions, sunitinib with
      SPAP may be a favorable cost-effective alternative for mRCC.

PMID- 22412885
TI  - HIV-1 disease progression is associated with bile-salt stimulated lipase (BSSL)
      gene polymorphism.
AB  - BACKGROUND: DC-SIGN expressed by dendritic cells captures HIV-1 resulting in
      trans-infection of CD4(+) T-lymphocytes. However, BSSL (bile-salt stimulated
      lipase) binding to DC-SIGN interferes with HIV-1 capture. DC-SIGN binding
      properties of BSSL associate with the polymorphic repeated motif of BSSL exon 11.
      Furthermore, BSSL binds to HIV-1 co-receptor CXCR4. We hypothesized that BSSL
      modulates HIV-1 disease progression and emergence of CXCR4 using HIV-1 (X4)
      variants. RESULTS: The relation between BSSL genotype and HIV-1 disease
      progression and emergence of X4 variants was studied using Kaplan Meier and
      multivariate Cox proportional hazard analysis in a cohort of HIV-1 infected men
      having sex with men (n = 334, with n = 130 seroconverters). We analyzed the
      association of BSSL genotype with set-point viral load and CD4 cell count, both
      pre-infection and post-infection at viral set-point. The number of repeats in
      BSSL exon 11 were highly variable ranging from 10 to 18 in seropositive
      individuals and from 5-17 in HRSN with 16 repeats being dominant (>80% carry at
      least one allele with 16 repeats). We defined 16 to 18 repeats as high (H) and
      less than 16 repeats as low (L) repeat numbers. Homozygosity for the high (H)
      repeat number BSSL genotype (HH) correlated with high CD4 cell numbers prior to
      infection (p = 0.007). In HIV-1 patients, delayed disease progression was linked
      to the HH BSSL genotype (RH = 0.462 CI = 0.282-0.757, p = 0.002) as was delayed
      emergence of X4 variants (RH = 0.525, 95% CI = 0.290-0.953, p = 0.034). The LH
      BSSL genotype, previously found to be associated with enhanced DC-SIGN binding of
      human milk, was identified to correlate with accelerated disease progression in
      our cohort of HIV-1 infected MSM (RH = 0.517, 95% CI = 0.328-0.818, p = 0.005).
      CONCLUSION: We identify BSSL as a marker for HIV-1 disease progression and
      emergence of X4 variants. Additionally, we identified a relation between BSSL
      genotype and CD4 cell counts prior to infection.

PMID- 22412886
TI  - Evaluation of cervical mucosa in transmission bottleneck during acute HIV-1
      infection using a cervical tissue-based organ culture.
AB  - BACKGROUND: Although there are different strains of HIV-1 in a chronically
      infected individual, only one or limited virus strains are successfully
      transmitted to a new individual. The reason for this "transmission bottleneck" is
      as yet unknown. METHODOLOGY/PRINCIPAL FINDINGS: A human cervical explant model
      was used to measure HIV-1 transmission efficiency of viral strains from chronic
      infections, and transmitter/founder variants. We also evaluated the genetic
      characteristics of HIV-1 variants in the inoculums compared to those transmitted
      across the cervical mucosa. Eight different HIV-1 isolates were used in this
      study, six chronic isolates and two transmitter/founder viruses. The transmission
      efficiency of the chronic and transmitter/founder virus isolates and the viral
      diversity of chronic isolates before and after viral transmission were assessed.
      The results indicate that transmitter/founder viruses did not display higher
      transmission efficiency than chronic HIV-1 isolates. Furthermore, no evidence for
      a difference in diversity was found between the inoculums and transmitted virus
      strains. Phylogenetic analysis indicated that the sequences of variants in the
      inoculums and those present in transmitted virus intermingled irrespective of co
      receptor usage. In addition, the inoculum and transmitted variants had a similar
      pairwise distance distribution. CONCLUSION: There was no selection of a single or
      limited number of viral variants during HIV-1 transmission across the cervical
      mucosa in the organ culture model, indicating that the cervical mucosa alone may
      not produce the transmission bottleneck of HIV-1 infection observed in vivo.

PMID- 22412887
TI  - The logic of fashion cycles.
AB  - Many cultural traits exhibit volatile dynamics, commonly dubbed fashions or fads.
      Here we show that realistic fashion-like dynamics emerge spontaneously if
      individuals can copy others' preferences for cultural traits as well as traits
      themselves. We demonstrate this dynamics in simple mathematical models of the
      diffusion, and subsequent abandonment, of a single cultural trait which
      individuals may or may not prefer. We then simulate the coevolution between many
      cultural traits and the associated preferences, reproducing power-law frequency
      distributions of cultural traits (most traits are adopted by few individuals for
      a short time, and very few by many for a long time), as well as correlations
      between the rate of increase and the rate of decrease of traits (traits that
      increase rapidly in popularity are also abandoned quickly and vice versa). We
      also establish that alternative theories, that fashions result from individuals
      signaling their social status, or from individuals randomly copying each other,
      do not satisfactorily reproduce these empirical observations.

PMID- 22412888
TI  - Low 2-dimensional CD4 T cell receptor affinity for myelin sets in motion delayed
      response kinetics.
AB  - T cells recognizing self-peptides that mediate autoimmune disease and those that
      are responsible for efficacious immunity against pathogens may differ in affinity
      for antigen due to central and peripheral tolerance mechanisms. Here we utilize
      prototypical self-reactive (myelin) and viral-specific (LCMV) T cells from T cell
      receptor (TCR) transgenic mice (2D2 and SMARTA, respectively) to explore affinity
      differences. The T cells responsive to virus possessed >10,000 fold higher 2D
      affinity as compared to the self-reactive T cells. Despite their dramatically
      lower affinity for their cognate ligand, 2D2 T cells respond with complete,
      albeit delayed, activation (proliferation and cytokine production). SMARTA
      activation occurs rapidly, achieving peak phosphorylation of p38 (1 minute), Erk
      (30 minutes), and Jun (3 hours) as well as CD69 and CD25 upregulation (3 and 6
      hours, respectively), with a corresponding early initiation of proliferation. 2D2
      stimulation with MOG results in altered signaling--no phospho-Erk or phospho-p38
      accumulation, significantly delayed activation kinetics of Jun (12 hours), and
      delayed but sustained SHP-1 activity--as well as delayed CD69 and CD25 expression
      (12-24 hours), and slow initiation of proliferation. This delay was not intrinsic
      to the 2D2 T cells, as a more potent antigen with >100-fold increased 2D affinity
      restored rapid response kinetics in line with those identified for the viral
      antigen. Taken together, these data demonstrate that time can offset low TCR
      affinity to attain full activation and suggest a mechanism by which low affinity
      T cells participate in autoimmune disease.

PMID- 22412889
TI  - Circumpolar diversity and geographic differentiation of mtDNA in the critically
      endangered Antarctic blue whale (Balaenoptera musculus intermedia).
AB  - The Antarctic blue whale (Balaenoptera musculus intermedia) was hunted to near
      extinction between 1904 and 1972, declining from an estimated initial abundance
      of more than 250,000 to fewer than 400. Here, we describe mtDNA control region
      diversity and geographic differentiation in the surviving population of the
      Antarctic blue whale, using 218 biopsy samples collected under the auspices of
      the International Whaling Commission (IWC) during research cruises from 1990
      2009. Microsatellite genotypes and mtDNA sequences identified 166 individuals
      among the 218 samples and documented movement of a small number of individuals,
      including a female that traveled at least 6,650 km or 131 degrees  longitude over
      four years. mtDNA sequences from the 166 individuals were aligned with published
      sequences from 17 additional individuals, resolving 52 unique haplotypes from a
      consensus length of 410 bp. From this minimum census, a rarefaction analysis
      predicted that only 72 haplotypes (95% CL, 64, 86) have survived in the
      contemporary population of Antarctic blue whales. However, haplotype diversity
      was relatively high (0.968+/-0.004), perhaps as a result of the longevity of blue
      whales and the relatively recent timing of the bottleneck. Despite the potential
      for circumpolar dispersal, we found significant differentiation in mtDNA
      diversity (F(ST) = 0.032, p<0.005) and microsatellite alleles (F(ST) = 0.005,
      p<0.05) among the six Antarctic Areas historically used by the IWC for management
      of blue whales.

PMID- 22412890
TI  - Haemophilus parasuis encodes two functional cytolethal distending toxins: CdtC
      contains an atypical cholesterol recognition/interaction region.
AB  - Haemophilus parasuis is the causative agent of Glasser's disease of pigs, a
      disease associated with fibrinous polyserositis, polyarthritis and meningitis. We
      report here H. parasuis encodes two copies of cytolethal distending toxins
      (Cdts), which these two Cdts showed the uniform toxin activity in vitro. We
      demonstrate that three Cdt peptides can form an active tripartite holotoxin that
      exhibits maximum cellular toxicity, and CdtA and CdtB form a more active toxin
      than CdtB and CdtC. Moreover, the cellular toxicity is associated with the
      binding of Cdt subunits to cells. Further analysis indicates that CdtC subunit
      contains an atypical cholesterol recognition/interaction amino acid consensus
      (CRAC) region. The mutation of CRAC site resulted in decreased cell toxicity.
      Finally, western blot analysis show all the 15 H. parasuis reference strains and
      109 clinical isolates expressed CdtB subunit, indicating that Cdt is a
      conservative putative virulence factor for H. parasuis. This is the first report
      of the molecular and cellular basis of Cdt host interactions in H. parasuis.

PMID- 22412891
TI  - Erwinia amylovora expresses fast and simultaneously hrp/dsp virulence genes
      during flower infection on apple trees.
AB  - BACKGROUND: Pathogen entry through host blossoms is the predominant infection
      pathway of the gram-negative bacterium Erwinia amylovora leading to manifestation
      of the disease fire blight. Like in other economically important plant pathogens,
      E. amylovora pathogenicity depends on a type III secretion system encoded by hrp
      genes. However, timing and transcriptional order of hrp gene expression during
      flower infections are unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using quantitative
      real-time PCR analyses, we addressed the questions of how fast, strong and
      uniform key hrp virulence genes and the effector dspA/E are expressed when
      bacteria enter flowers provided with the full defense mechanism of the apple
      plant. In non-invasive bacterial inoculations of apple flowers still attached to
      the tree, E. amylovora activated expression of key type III secretion genes in a
      narrow time window, mounting in a single expression peak of all investigated
      hrp/dspA/E genes around 24-48 h post inoculation (hpi). This single expression
      peak coincided with a single depression in the plant PR-1 expression at 24 hpi
      indicating transient manipulation of the salicylic acid pathway as one target of
      E. amylovora type III effectors. Expression of hrp/dspA/E genes was highly
      correlated to expression of the regulator hrpL and relative transcript abundances
      followed the ratio: hrpA>hrpN>hrpL>dspA/E. Acidic conditions (pH 4) in flower
      infections led to reduced virulence/effector gene expression without the typical
      expression peak observed under natural conditions (pH 7).
      CONCLUSION/SIGNIFICANCE: The simultaneous expression of hrpL, hrpA, hrpN, and the
      effector dspA/E during early floral infection indicates that speed and immediate
      effector transmission is important for successful plant invasion. When this
      delicate balance is disturbed, e.g., by acidic pH during infection, virulence
      gene expression is reduced, thus partly explaining the efficacy of acidification
      in fire blight control on a molecular level.

PMID- 22412892
TI  - Simulated impact of RTS,S/AS01 vaccination programs in the context of changing
      malaria transmission.
AB  - INTRODUCTION: The RTS,S/AS01 pre-erythrocytic malaria vaccine is in phase III
      clinical trials. It is critical to anticipate where and how it should be
      implemented if trials are successful. Such planning may be complicated by
      changing levels of malaria transmission. METHODS/RESULTS: Computer simulations
      were used to examine RTS,S/AS01 impact, using a vaccine profile based on phase II
      trial results, and assuming that protection decays only slowly. Settings were
      simulated in which baseline transmission (in the absence of vaccine) was fixed or
      varied between 2 and 20 infectious mosquito bites per person per annum (ibpa)
      over ten years. Four delivery strategies were studied: routine infant
      immunization (EPI), EPI plus infant catch-up, EPI plus school-based campaigns,
      and EPI plus mass campaigns. Impacts in changing transmission settings were
      similar to those in fixed settings. Assuming a persistent effect of vaccination,
      at 2 ibpa, the vaccine averted approximately 5-7 deaths per 1000 doses of vaccine
      when delivered via mass campaigns, but the benefit was less at higher
      transmission levels. EPI, catch-up and school-based strategies averted 2-3 deaths
      per 1000 doses in settings with 2 ibpa. In settings where transmission was
      decreasing or increasing, EPI, catch-up and school-based strategies averted
      approximately 3-4 deaths per 1000 doses. DISCUSSION: Where transmission is
      changing, it appears to be sufficient to consider simulations of pre-erythrocytic
      vaccine impact at a range of initial transmission levels. At 2 ibpa, mass
      campaigns averted the most deaths and reduced transmission, but this requires
      further study. If delivered via EPI, RTS,S/AS01 could avert approximately 6-11
      deaths per 1000 vaccinees in all examined settings, similar to estimates for
      pneumococcal conjugate vaccine in African infants. These results support
      RTS,S/AS01 implementation via EPI, for example alongside vector control
      interventions, providing that the phase III trials provide support for our
      assumptions about efficacy.

PMID- 22412893
TI  - Gene expression of the tumour suppressor LKB1 is mediated by Sp1, NF-Y and FOXO
      transcription factors.
AB  - The serine/threonine kinase LKB1 is a tumour suppressor that regulates multiple
      biological pathways, including cell cycle control, cell polarity and energy
      metabolism by direct phosphorylation of 14 different AMP-activated protein kinase
      (AMPK) family members. Although many downstream targets have been described, the
      regulation of LKB1 gene expression is still poorly understood. In this study, we
      performed a functional analysis of the human LKB1 upstream regulatory region. We
      used 200 base pair deletion constructs of the 5'-flanking region fused to a
      luciferase reporter to identify the core promoter. It encompasses nucleotides 
      345 to +52 relative to the transcription start site and coincides with a DNase I
      hypersensitive site. Based on extensive deletion and substitution mutant analysis
      of the LKB1 promoter, we identified four cis-acting elements which are critical
      for transcriptional activation. Using electrophoretic mobility shift assays as
      well as chromatin immunoprecipitations, we demonstrate that the transcription
      factors Sp1, NF-Y and two forkhead box O (FOXO) family members FOXO3 and FOXO4
      bind to these elements. Overexpression of these factors significantly increased
      the LKB1 promoter activity. Conversely, small interfering RNAs directed against
      NF-Y alpha and the two FOXO proteins greatly reduced endogenous LKB1 expression
      and phosphorylation of LKB1's main substrate AMPK in three different cell lines.
      Taken together, these results demonstrate that Sp1, NF-Y and FOXO transcription
      factors are involved in the regulation of LKB1 transcription.

PMID- 22412894
TI  - Mitochondrial pseudogenes in the nuclear genomes of Drosophila.
AB  - Mitochondrial pseudogenes in nuclear chromosomes (numts) have been detected in
      the genomes of a diverse range of eukaryotic species. However, the numt content
      of different genomes and their properties is not uniform, and study of these
      differences provides insight into the mechanisms and dynamics of genome evolution
      in different organisms. In the genus Drosophila, numts have previously only been
      identified on a genome-wide scale in the melanogaster subgroup. The present study
      extends the identification to 11 species of the Drosophila genus. We identify a
      total of 302 numts and show that the numt complement is highly variable in
      Drosophilids, ranging from just 4 in D. melanogaster to 67 in D. willistoni,
      broadly correlating with genome size. Many numts have undergone large-scale
      rearrangements in the nucleus, including interruptions, inversions, deletions and
      duplications of sequence of variable size. Estimating the age of the numts in the
      nucleus by phylogenetic tree reconstruction reveals the vast majority of numts to
      be recent gains, 90% having arisen on terminal branches of the species tree. By
      identifying paralogs and counting duplications among the extant numts we estimate
      that 23% of extant numts arose through post-insertion duplications. We estimate
      genus average rates of insertion of 0.75 per million years, and a duplication
      rate of 0.010 duplications per numt per million years.

PMID- 22412895
TI  - Invasive lionfish drive Atlantic coral reef fish declines.
AB  - Indo-Pacific lionfish (Pterois volitans and P. miles) have spread swiftly across
      the Western Atlantic, producing a marine predator invasion of unparalleled speed
      and magnitude. There is growing concern that lionfish will affect the structure
      and function of invaded marine ecosystems, however detrimental impacts on natural
      communities have yet to be measured. Here we document the response of native fish
      communities to predation by lionfish populations on nine coral reefs off New
      Providence Island, Bahamas. We assessed lionfish diet through stomach contents
      analysis, and quantified changes in fish biomass through visual surveys of
      lionfish and native fishes at the sites over time. Lionfish abundance increased
      rapidly between 2004 and 2010, by which time lionfish comprised nearly 40% of the
      total predator biomass in the system. The increase in lionfish abundance
      coincided with a 65% decline in the biomass of the lionfish's 42 Atlantic prey
      fishes in just two years. Without prompt action to control increasing lionfish
      populations, similar effects across the region may have long-term negative
      implications for the structure of Atlantic marine communities, as well as the
      societies and economies that depend on them.

PMID- 22412896
TI  - Involvement of complexin 2 in docking, locking and unlocking of different SNARE
      complexes during sperm capacitation and induced acrosomal exocytosis.
AB  - Acrosomal exocytosis (AE) is an intracellular multipoint fusion reaction of the
      sperm plasma membrane (PM) with the outer acrosomal membrane (OAM). This unique
      exocytotic event enables the penetration of the sperm through the zona pellucida
      of the oocyte. We previously observed a stable docking of OAM to the PM brought
      about by the formation of the trans-SNARE complex (syntaxin 1B, SNAP 23 and VAMP
      3). By using electron microscopy, immunochemistry and immunofluorescence
      techniques in combination with functional studies and proteomic approaches, we
      here demonstrate that calcium ionophore-induced AE results in the formation of
      unilamellar hybrid membrane vesicles containing a mixture of components
      originating from the two fused membranes. These mixed vesicles (MV) do not
      contain the earlier reported trimeric SNARE complex but instead possess a novel
      trimeric SNARE complex that contained syntaxin 3, SNAP 23 and VAMP 2, with an
      additional SNARE interacting protein, complexin 2. Our data indicate that the
      earlier reported raft and capacitation-dependent docking phenomenon between the
      PM and OAM allows a specific rearrangement of molecules between the two docked
      membranes and is involved in (1) recruiting SNAREs and complexin 2 in the newly
      formed lipid-ordered microdomains, (2) the assembly of a fusion-driving SNARE
      complex which executes Ca(2+)-dependent AE, (3) the disassembly of the earlier
      reported docking SNARE complex, (4) the recruitment of secondary zona binding
      proteins at the zona interacting sperm surface. The possibility to study separate
      and dynamic interactions between SNARE proteins, complexin and Ca(2+) which are
      all involved in AE make sperm an ideal model for studying exocytosis.

PMID- 22412897
TI  - Socio-economic position and type 2 diabetes risk factors: patterns in UK children
      of South Asian, black African-Caribbean and white European origin.
AB  - BACKGROUND: Socio-economic position (SEP) and ethnicity influence type 2 diabetes
      mellitus (T2DM) risk in adults. However, the influence of SEP on emerging T2DM
      risks in different ethnic groups and the contribution of SEP to ethnic
      differences in T2DM risk in young people have been little studied. We examined
      the relationships between SEP and T2DM risk factors in UK children of South
      Asian, black African-Caribbean and white European origin, using the official UK
      National Statistics Socio-economic Classification (NS-SEC) and assessed the
      extent to which NS-SEC explained ethnic differences in T2DM risk factors. METHODS
      AND FINDINGS: Cross-sectional school-based study of 4,804 UK children aged 9-10
      years, including anthropometry and fasting blood analytes (response rates 70%,
      68% and 58% for schools, individuals and blood measurements). Assessment of SEP
      was based on parental occupation defined using NS-SEC and ethnicity on parental
      self-report. Associations between NS-SEC and adiposity, insulin resistance (IR)
      and triglyceride differed between ethnic groups. In white Europeans, lower NS-SEC
      status was related to higher ponderal index (PI), fat mass index, IR and
      triglyceride (increases per NS-SEC decrement [95%CI] were 1.71% [0.75, 2.68],
      4.32% [1.24, 7.48], 5.69% [2.01, 9.51] and 3.17% [0.96, 5.42], respectively). In
      black African-Caribbeans, lower NS-SEC was associated with lower PI (-1.12%; [
      2.01, -0.21]), IR and triglyceride, while in South Asians there were no
      consistent associations between NS-SEC and T2DM risk factors. Adjustment for NS
      SEC did not appear to explain ethnic differences in T2DM risk factors, which were
      particularly marked in high NS-SEC groups. CONCLUSIONS: SEP is associated with
      T2DM risk factors in children but patterns of association differ by ethnic
      groups. Consequently, ethnic differences (which tend to be largest in affluent
      socio-economic groups) are not explained by NS-SEC. This suggests that strategies
      aimed at reducing social inequalities in T2DM risk are unlikely to reduce
      emerging ethnic differences in T2DM risk.

PMID- 22412898
TI  - Genetic characterization of a core set of a tropical maize race Tuxpeno for
      further use in maize improvement.
AB  - The tropical maize race Tuxpeno is a well-known race of Mexican dent germplasm
      which has greatly contributed to the development of tropical and subtropical
      maize gene pools. In order to investigate how it could be exploited in future
      maize improvement, a panel of maize germplasm accessions was assembled and
      characterized using genome-wide Single Nucleotide Polymorphism (SNP) markers.
      This panel included 321 core accessions of Tuxpeno race from the International
      Maize and Wheat Improvement Center (CIMMYT) germplasm bank collection, 94 CIMMYT
      maize lines (CMLs) and 54 U.S. Germplasm Enhancement of Maize (GEM) lines. The
      panel also included other diverse sources of reference germplasm: 14 U.S. maize
      landrace accessions, 4 temperate inbred lines from the U.S. and China, and 11
      CIMMYT populations (a total of 498 entries with 795 plants). Clustering analyses
      (CA) based on Modified Rogers Distance (MRD) clearly partitioned all 498 entries
      into their corresponding groups. No sub clusters were observed within the Tuxpeno
      core set. Various breeding strategies for using the Tuxpeno core set, based on
      grouping of the studied germplasm and genetic distance among them, were
      discussed. In order to facilitate sampling diversity within the Tuxpeno core, a
      minicore subset of 64 Tuxpeno accessions (20% of its usual size) representing the
      diversity of the core set was developed, using an approach combining phenotypic
      and molecular data. Untapped diversity represents further use of the Tuxpeno
      landrace for maize improvement through the core and/or minicore subset available
      to the maize community.

PMID- 22412899
TI  - Metabolic control by S6 kinases depends on dietary lipids.
AB  - Targeted deletion of S6 kinase (S6K) 1 in mice leads to higher energy expenditure
      and improved glucose metabolism. However, the molecular mechanisms controlling
      these effects remain to be fully elucidated. Here, we analyze the potential role
      of dietary lipids in regulating the mTORC1/S6K system. Analysis of S6K
      phosphorylation in vivo and in vitro showed that dietary lipids activate S6K, and
      this effect is not dependent upon amino acids. Comparison of male mice lacking
      S6K1 and 2 (S6K-dko) with wt controls showed that S6K-dko mice are protected
      against obesity and glucose intolerance induced by a high-fat diet. S6K-dko mice
      fed a high-fat diet had increased energy expenditure, improved glucose tolerance,
      lower fat mass gain, and changes in markers of lipid metabolism. Importantly,
      however, these metabolic phenotypes were dependent upon dietary lipids, with no
      such effects observed in S6K-dko mice fed a fat-free diet. These changes appear
      to be mediated via modulation of cellular metabolism in skeletal muscle, as shown
      by the expression of genes involved in energy metabolism. Taken together, our
      results suggest that the metabolic functions of S6K in vivo play a key role as a
      molecular interface connecting dietary lipids to the endogenous control of energy
      metabolism.

PMID- 22412900
TI  - Genetic biomarkers for ALS disease in transgenic SOD1(G93A) mice.
AB  - The pathophysiological mechanisms of both familial and sporadic Amyotrophic
      Lateral Sclerosis (ALS) are unknown, although growing evidence suggests that
      skeletal muscle tissue is a primary target of ALS toxicity. Skeletal muscle
      biopsies were performed on transgenic SOD1(G93A) mice, a mouse model of ALS, to
      determine genetic biomarkers of disease longevity. Mice were anesthetized with
      isoflurane, and three biopsy samples were obtained per animal at the three main
      stages of the disease. Transcriptional expression levels of seventeen genes,
      Ankrd1, Calm1, Col19a1, Fbxo32, Gsr, Impa1, Mef2c, Mt2, Myf5, Myod1, Myog, Nnt,
      Nogo A, Pax7, Rrad, Sln and Snx10, were tested in each muscle biopsy sample.
      Total RNA was extracted using TRIzol Reagent according to the manufacturer's
      protocol, and variations in gene expression were assayed by real-time PCR for all
      of the samples. The Pearson correlation coefficient was used to determine the
      linear correlation between transcriptional expression levels throughout disease
      progression and longevity. Consistent with the results obtained from total
      skeletal muscle of transgenic SOD1(G93A) mice and 74-day-old denervated mice,
      five genes (Mef2c, Gsr, Col19a1, Calm1 and Snx10) could be considered potential
      genetic biomarkers of longevity in transgenic SOD1(G93A) mice. These results are
      important because they may lead to the exploration of previously unexamined
      tissues in the search for new disease biomarkers and even to the application of
      these findings in human studies.

PMID- 22412901
TI  - Initial medical attention on patients with early-stage non-small cell lung
      cancer.
AB  - BACKGROUND: Detection of early stage non-small cell lung cancer (NSCLC) is
      commonly believed to be incidental. Understanding the reasons that caused initial
      detection of these patients is important for early diagnosis. However, these
      reasons are not well studied. METHODS: We retrospectively reviewed medical
      records of patients diagnosed with stage I or II NSCLC between 2000 and 2009 at
      UT MD Anderson Cancer Center. Information on suggestive LC-symptoms or other
      reasons that caused detection were extracted from patients' medical records. We
      applied univariate and multivariate analyses to evaluate the association of
      suggestive LC-symptoms with tumor size and patient survival. RESULTS: Of the 1396
      early stage LC patients, 733 (52.5%) presented with suggestive LC-symptoms as
      chief complaint. 347 (24.9%) and 287 (20.6%) were diagnosed because of regular
      check-ups and evaluations for other diseases, respectively. The proportion of
      suggestive LC-symptom-caused detection had a linear relationship with the tumor
      size (correlation 0.96; with p<.0001). After age, gender, race, smoking status,
      therapy, and stage adjustment, the symptom-caused detection showed no significant
      difference in overall and LC-specific survival when compared with the other (non
      symptom-caused) detection. CONCLUSION: Symptoms suggestive of LC are the number
      one reason that led to detection in early NSCLC. They were also associated with
      tumor size at diagnosis, suggesting early stage LC patients are developing
      symptoms. Presence of symptoms in early stages did not compromise survival. A
      symptom-based alerting system or guidelines may be worth of further study to
      benefit NSCLC high risk individuals.

PMID- 22412902
TI  - Relative stability of core groups in pollination networks in a biodiversity
      hotspot over four years.
AB  - Plants and their pollinators form pollination networks integral to the evolution
      and persistence of species in communities. Previous studies suggest that
      pollination network structure remains nested while network composition is highly
      dynamic. However, little is known about temporal variation in the structure and
      function of plant-pollinator networks, especially in species-rich communities
      where the strength of pollinator competition is predicted to be high. Here we
      quantify temporal variation of pollination networks over four consecutive years
      in an alpine meadow in the Hengduan Mountains biodiversity hotspot in China. We
      found that ranked positions and idiosyncratic temperatures of both plants and
      pollinators were more conservative between consecutive years than in non
      consecutive years. Although network compositions exhibited high turnover,
      generalized core groups--decomposed by a k-core algorithm--were much more stable
      than peripheral groups. Given the high rate of turnover observed, we suggest that
      identical plants and pollinators that persist for at least two successive years
      sustain pollination services at the community level. Our data do not support
      theoretical predictions of a high proportion of specialized links within species
      rich communities. Plants were relatively specialized, exhibiting less variability
      in pollinator composition at pollinator functional group level than at the
      species level. Both specialized and generalized plants experienced narrow
      variation in functional pollinator groups. The dynamic nature of pollination
      networks in the alpine meadow demonstrates the potential for networks to mitigate
      the effects of fluctuations in species composition in a high biodiversity area.

PMID- 22412903
TI  - Amplified genes may be overexpressed, unchanged, or downregulated in cervical
      cancer cell lines.
AB  - Several copy number-altered regions (CNAs) have been identified in the genome of
      cervical cancer, notably, amplifications of 3q and 5p. However, the contribution
      of copy-number alterations to cervical carcinogenesis is unresolved because
      genome-wide there exists a lack of correlation between copy-number alterations
      and gene expression. In this study, we investigated whether CNAs in the cell
      lines CaLo, CaSki, HeLa, and SiHa were associated with changes in gene
      expression. On average, 19.2% of the cell-line genomes had CNAs. However, only
      2.4% comprised minimal recurrent regions (MRRs) common to all the cell lines.
      Whereas 3q had limited common gains (13%), 5p was entirely duplicated
      recurrently. Genome-wide, only 15.6% of genes located in CNAs changed gene
      expression; in contrast, the rate in MRRs was up to 3 times this. Chr 5p was
      confirmed entirely amplified by FISH; however, maximum 33.5% of the explored
      genes in 5p were deregulated. In 3q, this rate was 13.4%. Even in 3q26, which had
      5 MRRs and 38.7% recurrently gained SNPs, the rate was only 15.1%. Interestingly,
      up to 19% of deregulated genes in 5p and 73% in 3q26 were downregulated,
      suggesting additional factors were involved in gene repression. The deregulated
      genes in 3q and 5p occurred in clusters, suggesting local chromatin factors may
      also influence gene expression. In regions amplified discontinuously,
      downregulated genes increased steadily as the number of amplified SNPs increased
      (p<0.01, Spearman's correlation). Therefore, partial gene amplification may
      function in silencing gene expression. Additional genes in 1q, 3q and 5p could be
      involved in cervical carcinogenesis, specifically in apoptosis. These include
      PARP1 in 1q, TNFSF10 and ECT2 in 3q and CLPTM1L, AHRR, PDCD6, and DAP in 5p.
      Overall, gene expression and copy-number profiles reveal factors other than gene
      dosage, like epigenetic or chromatin domains, may influence gene expression
      within the entirely amplified genome segments.

PMID- 22412904
TI  - Non-coding keratin variants associate with liver fibrosis progression in patients
      with hemochromatosis.
AB  - BACKGROUND: Keratins 8 and 18 (K8/K18) are intermediate filament proteins that
      protect the liver from various forms of injury. Exonic K8/K18 variants associate
      with adverse outcome in acute liver failure and with liver fibrosis progression
      in patients with chronic hepatitis C infection or primary biliary cirrhosis.
      Given the association of K8/K18 variants with end-stage liver disease and
      progression in several chronic liver disorders, we studied the importance of
      keratin variants in patients with hemochromatosis. METHODS: The entire K8/K18
      exonic regions were analyzed in 162 hemochromatosis patients carrying homozygous
      C282Y HFE (hemochromatosis gene) mutations. 234 liver-healthy subjects were used
      as controls. Exonic regions were PCR-amplified and analyzed using denaturing high
      performance liquid chromatography and DNA sequencing. Previously-generated
      transgenic mice overexpressing K8 G62C were studied for their susceptibility to
      iron overload. Susceptibility to iron toxicity of primary hepatocytes that
      express K8 wild-type and G62C was also assessed. RESULTS: We identified amino
      acid-altering keratin heterozygous variants in 10 of 162 hemochromatosis patients
      (6.2%) and non-coding heterozygous variants in 6 additional patients (3.7%). Two
      novel K8 variants (Q169E/R275W) were found. K8 R341H was the most common amino
      acid altering variant (4 patients), and exclusively associated with an intronic
      KRT8 IVS7+10delC deletion. Intronic, but not amino-acid-altering variants
      associated with the development of liver fibrosis. In mice, or ex vivo, the K8
      G62C variant did not affect iron-accumulation in response to iron-rich diet or
      the extent of iron-induced hepatocellular injury. CONCLUSION: In patients with
      hemochromatosis, intronic but not exonic K8/K18 variants associate with liver
      fibrosis development.

PMID- 22412905
TI  - Identification of ORC1/CDC6-interacting factors in Trypanosoma brucei reveals
      critical features of origin recognition complex architecture.
AB  - DNA replication initiates by formation of a pre-replication complex on sequences
      termed origins. In eukaryotes, the pre-replication complex is composed of the
      Origin Recognition Complex (ORC), Cdc6 and the MCM replicative helicase in
      conjunction with Cdt1. Eukaryotic ORC is considered to be composed of six
      subunits, named Orc1-6, and monomeric Cdc6 is closely related in sequence to
      Orc1. However, ORC has been little explored in protists, and only a single ORC
      protein, related to both Orc1 and Cdc6, has been shown to act in DNA replication
      in Trypanosoma brucei. Here we identify three highly diverged putative T. brucei
      ORC components that interact with ORC1/CDC6 and contribute to cell division. Two
      of these factors are so diverged that we cannot determine if they are eukaryotic
      ORC subunit orthologues, or are parasite-specific replication factors. The other
      we show to be a highly diverged Orc4 orthologue, demonstrating that this is one
      of the most widely conserved ORC subunits in protists and revealing it to be a
      key element of eukaryotic ORC architecture. Additionally, we have examined
      interactions amongst the T. brucei MCM subunits and show that this has the
      conventional eukaryotic heterohexameric structure, suggesting that divergence in
      the T. brucei replication machinery is limited to the earliest steps in origin
      licensing.

PMID- 22412906
TI  - Regulation of GIP and GLP1 receptor cell surface expression by N-glycosylation
      and receptor heteromerization.
AB  - In response to a meal, Glucose-dependent Insulinotropic Polypeptide (GIP) and
      Glucagon-like Peptide-1 (GLP-1) are released from gut endocrine cells into the
      circulation and interact with their cognate G-protein coupled receptors (GPCRs).
      Receptor activation results in tissue-selective pleiotropic responses that
      include augmentation of glucose-induced insulin secretion from pancreatic beta
      cells. N-glycosylation and receptor oligomerization are co-translational
      processes that are thought to regulate the exit of functional GPCRs from the ER
      and their maintenance at the plasma membrane. Despite the importance of these
      regulatory processes, their impact on functional expression of GIP and GLP-1
      receptors has not been well studied. Like many family B GPCRs, both the GIP and
      GLP-1 receptors possess a large extracellular N-terminus with multiple consensus
      sites for Asn-linked (N)-glycosylation. Here, we show that each of these Asn
      residues is glycosylated when either human receptor is expressed in Chinese
      hamster ovary cells. N-glycosylation enhances cell surface expression and
      function in parallel but exerts stronger control over the GIP receptor than the
      GLP-1 receptor. N-glycosylation mainly lengthens receptor half-life by reducing
      degradation in the endoplasmic reticulum. N-glycosylation is also required for
      expression of the GIP receptor at the plasma membrane and efficient GIP
      potentiation of glucose-induced insulin secretion from the INS-1 pancreatic beta
      cell line. Functional expression of a GIP receptor mutant lacking N-glycosylation
      is rescued by co-expressed wild type GLP1 receptor, which, together with data
      obtained using Bioluminescence Resonance Energy Transfer, suggests formation of a
      GIP-GLP1 receptor heteromer.

PMID- 22412907
TI  - Calbindin-D32k is localized to a subpopulation of neurons in the nervous system
      of the sea cucumber Holothuria glaberrima (Echinodermata).
AB  - Members of the calbindin subfamily serve as markers of subpopulations of neurons
      within the vertebrate nervous system. Although markers of these proteins are
      widely available and used, their application to invertebrate nervous systems has
      been very limited. In this study we investigated the presence and distribution of
      members of the calbindin subfamily in the sea cucumber Holothuria glaberrima
      (Selenka, 1867). Immunohistological experiments with antibodies made against rat
      calbindin 1, parvalbumin, and calbindin 2, showed that these antibodies labeled
      cells and fibers within the nervous system of H. glaberrima. Most of the cells
      and fibers were co-labeled with the neural-specific marker RN1, showing their
      neural specificity. These were distributed throughout all of the nervous
      structures, including the connective tissue plexi of the body wall and podia.
      Bioinformatics analyses of the possible antigen recognized by these markers
      showed that a calbindin 2-like protein present in the sea urchin
      Strongylocentrotus purpuratus, corresponded to the calbindin-D32k previously
      identified in other invertebrates. Western blots with anti-calbindin 1 and anti
      parvalbumin showed that these markers recognized an antigen of approximately 32
      kDa in homogenates of radial nerve cords of H. glaberrima and Lytechinus
      variegatus. Furthermore, immunoreactivity with anti-calbindin 1 and anti
      parvalbumin was obtained to a fragment of calbindin-D32k of H. glaberrima. Our
      findings suggest that calbindin-D32k is present in invertebrates and its sequence
      is more similar to the vertebrate calbindin 2 than to calbindin 1. Thus,
      characterization of calbindin-D32k in echinoderms provides an important view of
      the evolution of this protein family and represents a valuable marker to study
      the nervous system of invertebrates.

PMID- 22412908
TI  - Light-evoked somatosensory perception of transgenic rats that express
      channelrhodopsin-2 in dorsal root ganglion cells.
AB  - In vertebrate somatosensory systems, each mode of touch-pressure, temperature or
      pain is sensed by sensory endings of different dorsal root ganglion (DRG)
      neurons, which conducted to the specific cortical loci as nerve impulses.
      Therefore, direct electrical stimulation of the peripheral nerve endings causes
      an erroneous sensation to be conducted by the nerve. We have recently generated
      several transgenic lines of rat in which channelrhodopsin-2 (ChR2) transgene is
      driven by the Thy-1.2 promoter. In one of them, W-TChR2V4, some neurons were
      endowed with photosensitivity by the introduction of the ChR2 gene, coding an
      algal photoreceptor molecule. The DRG neurons expressing ChR2 were
      immunohistochemically identified using specific antibodies to the markers of
      mechanoreceptive or nociceptive neurons. Their peripheral nerve endings in the
      plantar skin as well as the central endings in the spinal cord were also
      examined. We identified that ChR2 is expressed in a certain population of large
      neurons in the DRG of W-TChR2V4. On the basis of their morphology and molecular
      markers, these neurons were classified as mechanoreceptive but not nociceptive.
      ChR2 was also distributed in their peripheral sensory nerve endings, some of
      which were closely associated with CK20-positive cells to form Merkel cell
      neurite complexes or with S-100-positive cells to form structures like Meissner's
      corpuscles. These nerve endings are thus suggested to be involved in the sensing
      of touch. Each W-TChR2V4 rat showed a sensory-evoked behavior in response to blue
      LED flashes on the plantar skin. It is thus suggested that each rat acquired an
      unusual sensory modality of sensing blue light through the skin as touch
      pressure. This light-evoked somatosensory perception should facilitate study of
      how the complex tactile sense emerges in the brain.

PMID- 22412909
TI  - Cell lineage specific distribution of H3K27 trimethylation accumulation in an in
      vitro model for human implantation.
AB  - Female mammals inactivate one of their two X-chromosomes to compensate for the
      difference in gene-dosage with males that have just one X-chromosome. X
      chromosome inactivation is initiated by the expression of the non-coding RNA
      Xist, which coats the X-chromosome in cis and triggers gene silencing. In early
      mouse development the paternal X-chromosome is initially inactivated in all cells
      of cleavage stage embryos (imprinted X-inactivation) followed by reactivation of
      the inactivated paternal X-chromosome exclusively in the epiblast precursors of
      blastocysts, resulting temporarily in the presence of two active X-chromosomes in
      this specific lineage. Shortly thereafter, epiblast cells randomly inactivate
      either the maternal or the paternal X-chromosome. XCI is accompanied by the
      accumulation of histone 3 lysine 27 trimethylation (H3K27me3) marks on the
      condensed X-chromosome. It is still poorly understood how XCI is regulated during
      early human development. Here we have investigated lineage development and the
      distribution of H3K27me3 foci in human embryos derived from an in-vitro model for
      human implantation. In this system, embryos are co-cultured on decidualized
      endometrial stromal cells up to day 8, which allows the culture period to be
      extended for an additional two days. We demonstrate that after the co-culture
      period, the inner cell masses have relatively high cell numbers and that the
      GATA4-positive hypoblast lineage and OCT4-positive epiblast cell lineage in these
      embryos have segregated. H3K27me3 foci were observed in ~25% of the trophectoderm
      cells and in ~7.5% of the hypoblast cells, but not in epiblast cells. In contrast
      with day 8 embryos derived from the co-cultures, foci of H3K27me3 were not
      observed in embryos at day 5 of development derived from regular IVF-cultures.
      These findings indicate that the dynamics of H3K27me3 accumulation on the X
      chromosome in human development is regulated in a lineage specific fashion.

PMID- 22412910
TI  - Direct interaction of the N-terminal domain of ribosomal protein S1 with protein
      S2 in Escherichia coli.
AB  - Despite of the high resolution structure available for the E. coli ribosome,
      hitherto the structure and localization of the essential ribosomal protein S1 on
      the 30 S subunit still remains to be elucidated. It was previously reported that
      protein S1 binds to the ribosome via protein-protein interaction at the two N
      terminal domains. Moreover, protein S2 was shown to be required for binding of
      protein S1 to the ribosome. Here, we present evidence that the N-terminal domain
      of S1 (amino acids 1-106; S1(106)) is necessary and sufficient for the
      interaction with protein S2 as well as for ribosome binding. We show that over
      production of protein S1(106) affects E. coli growth by displacing native protein
      S1 from its binding pocket on the ribosome. In addition, our data reveal that the
      coiled-coil domain of protein S2 (S2alpha(2)) is sufficient to allow protein S1
      to bind to the ribosome. Taken together, these data uncover the crucial elements
      required for the S1/S2 interaction, which is pivotal for translation initiation
      on canonical mRNAs in gram-negative bacteria. The results are discussed in terms
      of a model wherein the S1/S2 interaction surface could represent a possible
      target to modulate the selectivity of the translational machinery and thereby
      alter the translational program under distinct conditions.

PMID- 22412911
TI  - Environmental and organismal predictors of intraspecific variation in the
      stoichiometry of a neotropical freshwater fish.
AB  - The elemental composition of animals, or their organismal stoichiometry, is
      thought to constrain their contribution to nutrient recycling, their interactions
      with other animals, and their demographic rates. Factors that affect organismal
      stoichiometry are generally poorly understood, but likely reflect elemental
      investments in morphological features and life history traits, acting in concert
      with the environmental availability of elements. We assessed the relative
      contribution of organismal traits and environmental variability to the
      stoichiometry of an insectivorous Neotropical stream fish, Rivulus hartii. We
      characterized the influence of body size, life history phenotype, stage of
      maturity, and environmental variability on organismal stoichiometry in 6 streams
      that differ in a broad suite of environmental variables. The elemental
      composition of R. hartii was variable, and overlapped with the wide range of
      elemental composition documented across freshwater fish taxa. Average %P
      composition was ~3.2%(+/-0.6), average %N~10.7%(+/-0.9), and average %C~41.7%(+/
      3.1). Streams were the strongest predictor of organismal stoichiometry, and
      explained up to 18% of the overall variance. This effect appeared to be largely
      explained by variability in quality of basal resources such as epilithon N:P and
      benthic organic matter C:N, along with variability in invertebrate standing
      stocks, an important food source for R. hartii. Organismal traits were weak
      predictors of organismal stoichiometry in this species, explaining when combined
      up to 7% of the overall variance in stoichiometry. Body size was significantly
      and positively correlated with %P, and negatively with N:P, and C:P, and life
      history phenotype was significantly correlated with %C, %P, C:P and C:N. Our
      study suggests that spatial variability in elemental availability is more
      strongly correlated with organismal stoichiometry than organismal traits, and
      suggests that the stoichiometry of carnivores may not be completely buffered from
      environmental variability. We discuss the relevance of these findings to
      ecological stoichiometry theory.

PMID- 22412912
TI  - Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK
      activation: a contributor to the beneficial effects of coffee on diabetes.
AB  - Chlorogenic acid (CGA) has been shown to delay intestinal glucose absorption and
      inhibit gluconeogenesis. Our aim was to investigate the role of CGA in the
      regulation of glucose transport in skeletal muscle isolated from db/db mice and
      L6 skeletal muscle cells. Oral glucose tolerance test was performed on db/db mice
      treated with CGA and soleus muscle was isolated for 2-deoxyglucose transport
      study. 2DG transport was also examined in L6 myotubes with or without inhibitors
      such as wortmannin or compound c. AMPK was knocked down with AMPKalpha1/2 siRNA
      to study its effect on CGA-stimulated glucose transport. GLUT 4 translocation,
      phosphorylation of AMPK and Akt, AMPK activity, and association of IRS-1 and PI3K
      were investigated in the presence of CGA. In db/db mice, a significant decrease
      in fasting blood sugar was observed 10 minutes after the intraperitoneal
      administration of 250 mg/kg CGA and the effect persisted for another 30 minutes
      after the glucose challenge. Besides, CGA stimulated and enhanced both basal and
      insulin-mediated 2DG transports in soleus muscle. In L6 myotubes, CGA caused a
      dose- and time-dependent increase in glucose transport. Compound c and
      AMPKalpha1/2 siRNA abrogated the CGA-stimulated glucose transport. Consistent
      with these results, CGA was found to phosphorylate AMPK and ACC, consistent with
      the result of increased AMPK activities. CGA did not appear to enhance
      association of IRS-1 with p85. However, we observed activation of Akt by CGA.
      These parallel activations in turn increased translocation of GLUT 4 to plasma
      membrane. At 2 mmol/l, CGA did not cause any significant changes in viability or
      proliferation of L6 myotubes. Our data demonstrated for the first time that CGA
      stimulates glucose transport in skeletal muscle via the activation of AMPK. It
      appears that CGA may contribute to the beneficial effects of coffee on Type 2
      diabetes mellitus.

PMID- 22412913
TI  - Malaria vectors in Lake Victoria and adjacent habitats in western Kenya.
AB  - The prevalence of malaria among the residents of the Lake Victoria basin remains
      high. The environment associated with the lake may maintain a high number of
      malaria vectors. Lake habitats including water hyacinths have been suspected to
      be the source of vectors. This study investigated whether malaria vectors breed
      in the lake habitats and adjacent backwater pools. Anopheline larvae were
      collected within the littoral zone of the lake and adjacent pools located along
      approximately 24.3 km of the lakeshore in western Kenya, and their breeding sites
      characterized. Three primary vector species, Anopheles arabiensis, Anopheles
      gambiae s.s. and Anopheles funestus s.s., and three potential vectors, were found
      in the lake habitats. Unexpectedly, An. arabiensis was the most dominant vector
      species in the lake sampling sites. Its habitats were uncovered or covered with
      short grass. A potential secondary malaria vector, Anopheles rivulorum, dominated
      the water hyacinths in the lake. Most breeding sites in the lake were limited to
      areas that were surrounded by tall emergent plants, including trees, and those
      not exposed to waves. Nearly half of adjacent habitats were lagoons that were
      separated from the lake by sand bars. Lagoons contained a variety of
      microhabitats. Anopheles arabiensis dominated open habitats, whereas An. funestus
      s.s. was found mainly in vegetated habitats in lagoons. The current study
      confirmed that several breeding sites are associated with Lake Victoria. Given
      that Lake Victoria is the second largest lake in the world, the lake related
      habitats must be extensive; therefore, making targeted vector control difficult.
      Further exploration is necessary to estimate the effects of lake associated
      habitats on malaria transmission so as to inform a rational decision-making
      process for vector control.

PMID- 22412914
TI  - Commensal bacteria modulate innate immune responses of vaginal epithelial cell
      multilayer cultures.
AB  - The human vaginal microbiome plays a critical but poorly defined role in
      reproductive health. Vaginal microbiome alterations are associated with increased
      susceptibility to sexually-transmitted infections (STI) possibly due to related
      changes in innate defense responses from epithelial cells. Study of the impact of
      commensal bacteria on the vaginal mucosal surface has been hindered by current
      vaginal epithelial cell (VEC) culture systems that lack an appropriate interface
      between the apical surface of stratified squamous epithelium and the air-filled
      vaginal lumen. Therefore we developed a reproducible multilayer VEC culture
      system with an apical (luminal) air-interface that supported colonization with
      selected commensal bacteria. Multilayer VEC developed tight-junctions and other
      hallmarks of the vaginal mucosa including predictable proinflammatory cytokine
      secretion following TLR stimulation. Colonization of multilayers by common
      vaginal commensals including Lactobacillus crispatus, L. jensenii, and L.
      rhamnosus led to intimate associations with the VEC exclusively on the apical
      surface. Vaginal commensals did not trigger cytokine secretion but Staphylococcus
      epidermidis, a skin commensal, was inflammatory. Lactobacilli reduced cytokine
      secretion in an isolate-specific fashion following TLR stimulation. This
      tempering of inflammation offers a potential explanation for increased
      susceptibility to STI in the absence of common commensals and has implications
      for testing of potential STI preventatives.

PMID- 22412916
TI  - Disturbance and recovery of salt marsh arthropod communities following BP
      Deepwater Horizon oil spill.
AB  - Oil spills represent a major environmental threat to coastal wetlands, which
      provide a variety of critical ecosystem services to humanity. The U.S. Gulf of
      Mexico is a hub of oil and gas exploration activities that historically have
      impacted intertidal habitats such as salt marsh. Following the BP Deepwater
      Horizon oil spill, we sampled the terrestrial arthropod community and marine
      invertebrates found in stands of Spartina alterniflora, the most abundant plant
      in coastal salt marshes. Sampling occurred in 2010 as oil was washing ashore and
      a year later in 2011. In 2010, intertidal crabs and terrestrial arthropods
      (insects and spiders) were suppressed by oil exposure even in seemingly
      unaffected stands of plants; however, Littoraria snails were unaffected. One year
      later, crab and arthropods had largely recovered. Our work is the first attempt
      that we know of assessing vulnerability of the salt marsh arthropod community to
      oil exposure, and it suggests that arthropods are both quite vulnerable to oil
      exposure and quite resilient, able to recover from exposure within a year if host
      plants remain healthy.

PMID- 22412915
TI  - Prioritizing risks and uncertainties from intentional release of selected
      Category A pathogens.
AB  - This paper synthesizes available information on five Category A pathogens
      (Bacillus anthracis, Yersinia pestis, Francisella tularensis, Variola major and
      Lassa) to develop quantitative guidelines for how environmental pathogen
      concentrations may be related to human health risk in an indoor environment. An
      integrated model of environmental transport and human health exposure to
      biological pathogens is constructed which 1) includes the effects of
      environmental attenuation, 2) considers fomite contact exposure as well as
      inhalational exposure, and 3) includes an uncertainty analysis to identify key
      input uncertainties, which may inform future research directions. The findings
      provide a framework for developing the many different environmental standards
      that are needed for making risk-informed response decisions, such as when
      prophylactic antibiotics should be distributed, and whether or not a contaminated
      area should be cleaned up. The approach is based on the assumption of uniform
      mixing in environmental compartments and is thus applicable to areas sufficiently
      removed in time and space from the initial release that mixing has produced
      relatively uniform concentrations. Results indicate that when pathogens are
      released into the air, risk from inhalation is the main component of the overall
      risk, while risk from ingestion (dermal contact for B. anthracis) is the main
      component of the overall risk when pathogens are present on surfaces.
      Concentrations sampled from untracked floor, walls and the filter of heating
      ventilation and air conditioning (HVAC) system are proposed as indicators of
      previous exposure risk, while samples taken from touched surfaces are proposed as
      indicators of future risk if the building is reoccupied. A Monte Carlo
      uncertainty analysis is conducted and input-output correlations used to identify
      important parameter uncertainties. An approach is proposed for integrating these
      quantitative assessments of parameter uncertainty with broader, qualitative
      considerations to identify future research priorities.

PMID- 22412917
TI  - Association of natural intake of dietary plant sterols with carotid intima-media
      thickness and blood lipids in Chinese adults: a cross-section study.
AB  - BACKGROUND: Many studies showed a moderate cholesterol-lowering effect of plant
      sterols (PS), but increased circulating PS might be atherogenic. We evaluated the
      associations between natural dietary intake of PS and carotid intima-media
      thickness (IMT) and serum lipids. METHODOLOGY/PRINCIPAL FINDINGS: This community
      based cross-sectional study included 1160 men and 2780 women aged 31-75 years.
      Dietary intakes were assessed using a food-frequency questionnaire. The IMTs at
      the common, bifurcation and internal carotid artery segments, and fasting serum
      total (TC), LDL (LDLc) and HDL (HDLc) cholesterol, and triglycerides (TG) were
      determined. After adjusting for potential covariates, multivariate analysis
      showed a dose-dependent inverse association of total PS intake with serum TC,
      LDLc, non-HDLc in women (P<0.001) and in men (P<0.05). As compared to the lowest
      quartile of PS intake (<206 mg/d), the multivariate-adjusted means of TC, LDLc
      and non-HDLc in the highest quartile of PS intake (447 mg/d) decreased by 5.0%,
      6.2% and 6.5% in women (P<0.005), and by 6.4%, 7.1% and 6.7% (P>0.05) in men.
      Although the IMTs tended to be lower with greater intake of dietary PS, only
      small differences in the left internal IMT between the highest and lowest groups
      were observed among men (-7.6%) and women (-5.1%) (P<0.05). The multivariate
      analysis showed no significant mean differences among the PS groups in HDLc, TG
      and IMTs at other studied sites among men and women (all P>0.05). CONCLUSIONS:
      Greater PS consumption from natural diets is associated with lower serum total,
      LDL, non-HDL cholesterol and with thinner left internal IMT in women and men.

PMID- 22412918
TI  - Tractography delineates microstructural changes in the trigeminal nerve after
      focal radiosurgery for trigeminal neuralgia.
AB  - PURPOSE: Focal radiosurgery is a common treatment modality for trigeminal
      neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment
      effectiveness is primarily clinical, given the paucity of investigational tools
      to assess trigeminal nerve changes. Since diffusion tensor imaging (DTI) provides
      information on white matter microstructure, we explored the feasibility of
      trigeminal nerve tractography and assessment of DTI parameters to study
      microstructural changes after treatment. We hypothesized that trigeminal
      tractography provides more information than 2D-MR imaging, allowing detection of
      unique, focal changes in the target area after radiosurgery. Changes in specific
      diffusivities may provide insight into the mechanism of action of radiosurgery on
      the trigeminal nerve. METHODS AND MATERIALS: Five TN patients (4 females, 1 male,
      average age 67 years) treated with Gamma Knife radiosurgery, 80 Gy/100% isodose
      line underwent 3Tesla MR trigeminal nerve tractography before and sequentially up
      to fourteen months after treatment. Fractional anisotropy (FA), radial (RD) and
      axial (AD) diffusivities were calculated for the radiosurgical target area
      defined as the region-of-interest. Areas outside target and the contralateral
      nerve served as controls. RESULTS: Trigeminal tractography accurately detected
      the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the
      target with no significant change in FA outside the target, demonstrating highly
      focal changes after treatment. RD but not AD changed markedly, suggesting that
      radiosurgery primarily affects myelin. Tractography was more sensitive than
      conventional gadolinium-enhanced post-treatment MR, since FA changes were
      detected regardless of trigeminal nerve enhancement. In subjects with long term
      follow-up, recovery of FA/RD correlated with pain recurrence. CONCLUSIONS: DTI
      parameters accurately detect the effects of focal radiosurgery on the trigeminal
      nerve, serving as an in vivo imaging tool to study TN. This study is a proof of
      principle for further assessment of DTI parameters to understand the
      pathophysiology of TN and treatment effects.

PMID- 22412919
TI  - Geldanamycin derivative ameliorates high fat diet-induced renal failure in
      diabetes.
AB  - Diabetic nephropathy is a serious complication of longstanding diabetes and its
      pathogenesis remains unclear. Oxidative stress may play a critical role in the
      pathogenesis and progression of diabetic nephropathy. Our previous studies have
      demonstrated that polyunsaturated fatty acids (PUFA) induce peroxynitrite
      generation in primary human kidney mesangial cells and heat shock protein 90beta1
      (hsp90beta1) is indispensable for the PUFA action. Here we investigated the
      effects of high fat diet (HFD) on kidney function and structure of db/db mice, a
      widely used rodent model of type 2 diabetes. Our results indicated that HFD
      dramatically increased the 24 h-urine output and worsened albuminuria in db/db
      mice. Discontinuation of HFD reversed the exacerbated albuminuria but not the
      increased urine output. Prolonged HFD feeding resulted in early death of db/db
      mice, which was associated with oliguria and anuria. Treatment with the
      geldanamycin derivative, 17-(dimethylaminoehtylamino)-17-demethoxygeldanamycin
      (17-DMAG), an hsp90 inhibitor, preserved kidney function, and ameliorated
      glomerular and tubular damage by HFD. 17-DMAG also significantly extended
      survival of the animals and protected them from the high mortality associated
      with renal failure. The benefit effect of 17-DMAG on renal function and structure
      was associated with a decreased level of kidney nitrotyrosine and a diminished
      kidney mitochondrial Ca(2+) efflux in HFD-fed db/db mice. These results suggest
      that hsp90beta1 is a potential target for the treatment of nephropathy and renal
      failure in diabetes.

PMID- 22412920
TI  - Integrated epigenome profiling of repressive histone modifications, DNA
      methylation and gene expression in normal and malignant urothelial cells.
AB  - Epigenetic regulation of gene expression is commonly altered in human cancer. We
      have observed alterations of DNA methylation and microRNA expression that reflect
      the biology of bladder cancer. This common disease arises by distinct pathways
      with low and high-grade differentiation. We hypothesized that epigenetic gene
      regulation reflects an interaction between histone and DNA modifications, and
      differences between normal and malignant urothelial cells represent carcinogenic
      events within bladder cancer. To test this we profiled two repressive histone
      modifications (H3K9m3 and H3K27m3) using ChIP-Seq, cytosine methylation using
      MeDIP and mRNA expression in normal and malignant urothelial cell lines. In genes
      with low expression we identified H3K27m3 and DNA methylation each in 20-30% of
      genes and both marks in 5% of genes. H3K9m3 was detected in 5-10% of genes but
      was not associated with overall expression. DNA methylation was more closely
      related to gene expression in malignant than normal cells. H3K27m3 was the
      epigenetic mark most specifically correlated to gene silencing. Our data suggest
      that urothelial carcinogenesis is accompanied by a loss of control of both DNA
      methylation and H3k27 methylation. From our observations we identified a panel of
      genes with cancer specific-epigenetic mediated aberrant expression including
      those with reported carcinogenic functions and members potentially mediating a
      positive epigenetic feedback loop. Pathway enrichment analysis revealed genes
      marked by H3K9m3 were involved with cell homeostasis, those marked by H3K27m3
      mediated pro-carcinogenic processes and those marked with cytosine methylation
      were mixed in function. In 150 normal and malignant urothelial samples, our gene
      panel correctly estimated expression in 65% of its members. Hierarchical
      clustering revealed that this gene panel stratified samples according to the
      presence and phenotype of bladder cancer.

PMID- 22412921
TI  - HIV-1 promotes intake of Leishmania parasites by enhancing phosphatidylserine
      mediated, CD91/LRP-1-dependent phagocytosis in human macrophages.
AB  - Over the past decade, the number of reported human immunodeficiency virus type-1
      (HIV-1)/Leishmania co-infections has risen dramatically, particularly in regions
      where both diseases are endemic. Although it is known that HIV-1 infection leads
      to an increase in susceptibility to Leishmania infection and leishmaniasis
      relapse, little remains known on how HIV-1 contributes to Leishmania
      parasitaemia. Both pathogens infect human macrophages, and the intracellular
      growth of Leishmania is increased by HIV-1 in co-infected cultures. We now report
      that uninfected bystander cells, not macrophages productively infected with HIV
      1, account for enhanced phagocytosis and higher multiplication of Leishmania
      parasites. This effect can be driven by HIV-1 Tat protein and transforming growth
      factor-beta (TGF-beta). Furthermore, we show for the first time that HIV-1
      infection increases surface expression of phosphatidylserine receptor CD91/LRP-1
      on human macrophages, thereby leading to a Leishmania uptake by uninfected
      bystander cells in HIV-1-infected macrophage populations. The more important
      internalization of parasites is due to interactions between the scavenger
      receptor CD91/LRP-1 and phosphatidylserine residues exposed at the surface of
      Leishmania. We determined also that enhanced CD91/LRP-1 surface expression occurs
      rapidly following HIV-1 infection, and is triggered by the activation of
      extracellular TGF-beta. Thus, these results establish an intricate link between
      HIV-1 infection, Tat, surface CD91/LRP-1, TGF-beta, and enhanced Leishmania
      phosphatidylserine-mediated phagocytosis.

PMID- 22412922
TI  - Effects of different correlation metrics and preprocessing factors on small-world
      brain functional networks: a resting-state functional MRI study.
AB  - Graph theoretical analysis of brain networks based on resting-state functional
      MRI (R-fMRI) has attracted a great deal of attention in recent years. These
      analyses often involve the selection of correlation metrics and specific
      preprocessing steps. However, the influence of these factors on the topological
      properties of functional brain networks has not been systematically examined.
      Here, we investigated the influences of correlation metric choice (Pearson's
      correlation versus partial correlation), global signal presence (regressed or
      not) and frequency band selection [slow-5 (0.01-0.027 Hz) versus slow-4 (0.027
      0.073 Hz)] on the topological properties of both binary and weighted brain
      networks derived from them, and we employed test-retest (TRT) analyses for
      further guidance on how to choose the "best" network modeling strategy from the
      reliability perspective. Our results show significant differences in global
      network metrics associated with both correlation metrics and global signals.
      Analysis of nodal degree revealed differing hub distributions for brain networks
      derived from Pearson's correlation versus partial correlation. TRT analysis
      revealed that the reliability of both global and local topological properties are
      modulated by correlation metrics and the global signal, with the highest
      reliability observed for Pearson's-correlation-based brain networks without
      global signal removal (WOGR-PEAR). The nodal reliability exhibited a spatially
      heterogeneous distribution wherein regions in association and limbic/paralimbic
      cortices showed moderate TRT reliability in Pearson's-correlation-based brain
      networks. Moreover, we found that there were significant frequency-related
      differences in topological properties of WOGR-PEAR networks, and brain networks
      derived in the 0.027-0.073 Hz band exhibited greater reliability than those in
      the 0.01-0.027 Hz band. Taken together, our results provide direct evidence
      regarding the influences of correlation metrics and specific preprocessing
      choices on both the global and nodal topological properties of functional brain
      networks. This study also has important implications for how to choose reliable
      analytical schemes in brain network studies.

PMID- 22412923
TI  - Distinguishing type 2 diabetes from type 1 diabetes in African American and
      Hispanic American pediatric patients.
AB  - OBJECTIVE: To test the hypothesis that clinical observations made at patient
      presentation can distinguish type 2 diabetes (T2D) from type 1 diabetes (T1D) in
      pediatric patients aged 2 to 18. SUBJECTS AND METHODS: Medical records of 227
      African American and 112 Hispanic American pediatric patients diagnosed as T1D or
      T2D were examined to compare parameters in the two diseases. Age at presentation,
      BMI z-score, and gender were the variables used in logistic regression analysis
      to create models for T2D prediction. RESULTS: The regression-based model created
      from African American data had a sensitivity of 92% and a specificity of 89%;
      testing of a replication cohort showed 91% sensitivity and 93% specificity. A
      model based on the Hispanic American data showed 92% sensitivity and 90%
      specificity. Similarities between African American and Hispanic American patients
      include: (1) age at onset for both T1D and T2D decreased from the 1980s to the
      2000s; (2) risk of T2D increased markedly with obesity. Racial/ethnic-specific
      observations included: (1) in African American patients, the proportion of
      females was significantly higher than that of males for T2D compared to T1D
      (p<0.0001); (2) in Hispanic Americans, the level of glycated hemoglobin (HbA1c)
      was significantly higher in T1D than in T2D (p<0.002) at presentation; (3) the
      strongest contributor to T2D risk was female gender in African Americans, while
      the strongest contributor to T2D risk was BMI z-score in Hispanic Americans.
      CONCLUSIONS: Distinction of T2D from T1D at patient presentation was possible
      with good sensitivity and specificity using only three easily-assessed variables:
      age, gender, and BMI z-score. In African American pediatric diabetes patients,
      gender was the strongest predictor of T2D, while in Hispanic patients, BMI z
      score was the strongest predictor. This suggests that race/ethnic specific models
      may be useful to optimize distinction of T1D from T2D at presentation.

PMID- 22412924
TI  - Evolution of JAK-STAT pathway components: mechanisms and role in immune system
      development.
AB  - BACKGROUND: Lying downstream of a myriad of cytokine receptors, the Janus kinase
      (JAK)-Signal transducer and activator of transcription (STAT) pathway is pivotal
      for the development and function of the immune system, with additional important
      roles in other biological systems. To gain further insight into immune system
      evolution, we have performed a comprehensive bioinformatic analysis of the JAK
      STAT pathway components, including the key negative regulators of this pathway,
      the SH2-domain containing tyrosine phosphatase (SHP), Protein inhibitors against
      Stats (PIAS), and Suppressor of cytokine signaling (SOCS) proteins across a
      diverse range of organisms. RESULTS: Our analysis has demonstrated significant
      expansion of JAK-STAT pathway components co-incident with the emergence of
      adaptive immunity, with whole genome duplication being the principal mechanism
      for generating this additional diversity. In contrast, expansion of upstream
      cytokine receptors appears to be a pivotal driver for the differential
      diversification of specific pathway components. CONCLUSION: Diversification of
      JAK-STAT pathway components during early vertebrate development occurred
      concurrently with a major expansion of upstream cytokine receptors and two rounds
      of whole genome duplications. This produced an intricate cell-cell communication
      system that has made a significant contribution to the evolution of the immune
      system, particularly the emergence of adaptive immunity.

PMID- 22412925
TI  - Mesenchymal stem cells transfer mitochondria to the cells with virtually no
      mitochondrial function but not with pathogenic mtDNA mutations.
AB  - It has been reported that human mesenchymal stem cells (MSCs) can transfer
      mitochondria to the cells with severely compromised mitochondrial function. We
      tested whether the reported intercellular mitochondrial transfer could be
      replicated in different types of cells or under different experimental
      conditions, and tried to elucidate possible mechanism. Using biochemical
      selection methods, we found exponentially growing cells in restrictive media
      (uridine(-) and bromodeoxyuridine [BrdU](+)) during the coculture of MSCs
      (uridine-independent and BrdU-sensitive) and 143B-derived cells with severe
      mitochondrial dysfunction induced by either long-term ethidium bromide treatment
      or short-term rhodamine 6G (R6G) treatment (uridine-dependent but BrdU
      resistant). The exponentially growing cells had nuclear DNA fingerprint patterns
      identical to 143B, and a sequence of mitochondrial DNA (mtDNA) identical to the
      MSCs. Since R6G causes rapid and irreversible damage to mitochondria without the
      removal of mtDNA, the mitochondrial function appears to be restored through a
      direct transfer of mitochondria rather than mtDNA alone. Conditioned media, which
      were prepared by treating mtDNA-less 143B rho(0) cells under uridine-free
      condition, induced increased chemotaxis in MSC, which was also supported by
      transcriptome analysis. Cytochalasin B, an inhibitor of chemotaxis and
      cytoskeletal assembly, blocked mitochondrial transfer phenomenon in the above
      condition. However, we could not find any evidence of mitochondrial transfer to
      the cells harboring human pathogenic mtDNA mutations (A3243G mutation or 4,977 bp
      deletion). Thus, the mitochondrial transfer is limited to the condition of a near
      total absence of mitochondrial function. Elucidation of the mechanism of
      mitochondrial transfer will help us create a potential cell therapy-based
      mitochondrial restoration or mitochondrial gene therapy for human diseases caused
      by mitochondrial dysfunction.

PMID- 22412926
TI  - Nitric oxide facilitates delivery and mediates improved outcome of autologous
      bone marrow mononuclear cells in a rodent stroke model.
AB  - BACKGROUND: Bone marrow mononuclear cells (MNC) represent an investigational
      treatment for stroke. The objective of this study was to determine the relevance
      of vasoactive mediators, generated in response to MNC injection, as factors
      regulating cerebral perfusion (CP), the biodistribution of MNC, and outcome in
      stroke. METHODS: Long Evans rats underwent transient middle cerebral artery
      occlusion. MNC were extracted from the bone marrow at 22 hrs and injected via the
      internal carotid artery or the femoral vein 2 hours later. CP was measured with
      MRI or continuous laser Doppler flowmetry. Serum samples were collected to
      measure vasoactive mediators. Animals were treated with the Nitric Oxide (NO)
      inhibitor, L-NAME, to establish the relevance of NO-signaling to the effect of
      MNC. Lesion size, MNC biodistribution, and neurological deficits were assessed.
      RESULTS: CP transiently increased in the peri-infarct region within 30 min after
      injecting MNC compared to saline or fibroblast control. This CP increase
      corresponded temporarily to serum NO elevation and was abolished by L-NAME. Pre
      treatment with L-NAME reduced brain penetration of MNC and prevented MNC from
      reducing infarct lesion size and neurological deficits. CONCLUSIONS: NO
      generation in response to MNC may represent a mechanism underlying how MNC enter
      the brain, reduce lesion size, and improve outcome in ischemic stroke.

PMID- 22412927
TI  - Rugged single domain antibody detection elements for Bacillus anthracis spores
      and vegetative cells.
AB  - Significant efforts to develop both laboratory and field-based detection assays
      for an array of potential biological threats started well before the anthrax
      attacks of 2001 and have continued with renewed urgency following. While numerous
      assays and methods have been explored that are suitable for laboratory
      utilization, detection in the field is often complicated by requirements for
      functionality in austere environments, where limited cold-chain facilities exist.
      In an effort to overcome these assay limitations for Bacillus anthracis, one of
      the most recognizable threats, a series of single domain antibodies (sdAbs) were
      isolated from a phage display library prepared from immunized llamas.
      Characterization of target specificity, affinity, and thermal stability was
      conducted for six sdAb families isolated from rounds of selection against the
      bacterial spore. The protein target for all six sdAb families was determined to
      be the S-layer protein EA1, which is present in both vegetative cells and
      bacterial spores. All of the sdAbs examined exhibited a high degree of
      specificity for the target bacterium and its spore, with affinities in the
      nanomolar range, and the ability to refold into functional antigen-binding
      molecules following several rounds of thermal denaturation and refolding. This
      research demonstrates the capabilities of these sdAbs and their potential for
      integration into current and developing assays and biosensors.

PMID- 22412928
TI  - Priming picture naming with a semantic task: an fMRI investigation.
AB  - Prior semantic processing can enhance subsequent picture naming performance, yet
      the neurocognitive mechanisms underlying this effect and its longevity are
      unknown. This functional magnetic resonance imaging study examined whether
      different neurological mechanisms underlie short-term (within minutes) and long
      term (within days) facilitation effects from a semantic task in healthy older
      adults. Both short- and long-term facilitated items were named significantly
      faster than unfacilitated items, with short-term items significantly faster than
      long-term items. Region of interest results identified decreased activity for
      long-term facilitated items compared to unfacilitated and short-term facilitated
      items in the mid-portion of the middle temporal gyrus, indicating lexical
      semantic priming. Additionally, in the whole brain results, increased activity
      for short-term facilitated items was identified in regions previously linked to
      episodic memory and object recognition, including the right lingual gyrus
      (extending to the precuneus region) and the left inferior occipital gyrus
      (extending to the left fusiform region). These findings suggest that distinct
      neurocognitive mechanisms underlie short- and long-term facilitation of picture
      naming by a semantic task, with long-term effects driven by lexical-semantic
      priming and short-term effects by episodic memory and visual object recognition
      mechanisms.

PMID- 22412929
TI  - Accelerated evolution of mitochondrial but not nuclear genomes of Hymenoptera:
      new evidence from crabronid wasps.
AB  - Mitochondrial genes in animals are especially useful as molecular markers for the
      reconstruction of phylogenies among closely related taxa, due to the generally
      high substitution rates. Several insect orders, notably Hymenoptera and
      Phthiraptera, show exceptionally high rates of mitochondrial molecular evolution,
      which has been attributed to the parasitic lifestyle of current or ancestral
      members of these taxa. Parasitism has been hypothesized to entail frequent
      population bottlenecks that increase rates of molecular evolution by reducing the
      efficiency of purifying selection. This effect should result in elevated
      substitution rates of both nuclear and mitochondrial genes, but to date no
      extensive comparative study has tested this hypothesis in insects. Here we report
      the mitochondrial genome of a crabronid wasp, the European beewolf (Philanthus
      triangulum, Hymenoptera, Crabronidae), and we use it to compare evolutionary
      rates among the four largest holometabolous insect orders (Coleoptera, Diptera,
      Hymenoptera, Lepidoptera) based on phylogenies reconstructed with whole
      mitochondrial genomes as well as four single-copy nuclear genes (18S rRNA,
      arginine kinase, wingless, phosphoenolpyruvate carboxykinase). The mt-genome of
      P. triangulum is 16,029 bp in size with a mean A+T content of 83.6%, and it
      encodes the 37 genes typically found in arthropod mt genomes (13 protein-coding,
      22 tRNA, and two rRNA genes). Five translocations of tRNA genes were discovered
      relative to the putative ancestral genome arrangement in insects, and the unusual
      start codon TTG was predicted for cox2. Phylogenetic analyses revealed
      significantly longer branches leading to the apocritan Hymenoptera as well as the
      Orussoidea, to a lesser extent the Cephoidea, and, possibly, the Tenthredinoidea
      than any of the other holometabolous insect orders for all mitochondrial but none
      of the four nuclear genes tested. Thus, our results suggest that the ancestral
      parasitic lifestyle of Apocrita is unlikely to be the major cause for the
      elevated substitution rates observed in hymenopteran mitochondrial genomes.

PMID- 22412930
TI  - Normalization of the lymph node T cell stromal microenvironment in lpr/lpr mice
      is associated with SU5416-induced reduction in autoantibodies.
AB  - The vascular-stromal elements of lymph nodes can play important roles in
      regulating the activities of the lymphocytes within. During model immune
      responses, the vascular-stromal compartment has been shown to undergo
      proliferative expansion and functional alterations. The state of the vascular
      stromal compartment and the potential importance of this compartment in a
      spontaneous, chronic model of autoimmunity have not been well studied. Here, we
      characterize the vascular expansion in MRL-lpr/lpr lymph nodes and attempt to ask
      whether inhibiting this expansion can interfere with autoantibody generation. We
      show that characteristics of vascular expansion in enlarging MRL-lpr/lpr lymph
      nodes resemble that of the VEGF-dependent expansion that occurs in wild-type mice
      after model immunization. Surprisingly, treatment with SU5416, an inhibitor of
      VEGF and other receptor tyrosine kinases, did not have sustained effects in
      inhibiting vascular growth, but attenuated the anti-dsDNA response and altered
      the phenotype of the double negative T cells that are expanded in these mice. In
      examining for anatomic correlates of these immunologic changes, we found that the
      double negative T cells are localized within ectopic follicles around a central B
      cell patch and that these T cell-rich areas lack the T zone stromal protein ER
      TR7 as well as other elements of a normal T zone microenvironment. SU5416
      treatment disrupted these follicles and normalized the association between T zone
      microenvironmental elements and T cell-rich areas. Recent studies have shown a
      regulatory role for T zone stromal elements. Thus, our findings of the
      association of anti-dsDNA responses, double negative T cell phenotype, and
      altered lymphocyte microenvironment suggest the possibility that lymphocyte
      localization in ectopic follicles protects them from regulation by T zone stromal
      elements and functions to maintain autoimmune responses. Potentially, altering
      the lymphocyte microenvironment that is set up by the vascular-stromal
      compartment can be a means by which to control undesired autoimmune responses.

PMID- 22412931
TI  - Butyrate attenuates lipopolysaccharide-induced inflammation in intestinal cells
      and Crohn's mucosa through modulation of antioxidant defense machinery.
AB  - Oxidative stress plays an important role in the pathogenesis of inflammatory
      bowel disease (IBD), including Crohn's disease (CrD). High levels of Reactive
      Oxygen Species (ROS) induce the activation of the redox-sensitive nuclear
      transcription factor kappa-B (NF-kappaB), which in turn triggers the inflammatory
      mediators. Butyrate decreases pro-inflammatory cytokine expression by the lamina
      propria mononuclear cells in CrD patients via inhibition of NF-kappaB activation,
      but how it reduces inflammation is still unclear. We suggest that butyrate
      controls ROS mediated NF-kappaB activation and thus mucosal inflammation in
      intestinal epithelial cells and in CrD colonic mucosa by triggering intracellular
      antioxidant defense systems. Intestinal epithelial Caco-2 cells and colonic
      mucosa from 14 patients with CrD and 12 controls were challenged with or without
      lipopolysaccaride from Escherichia coli (EC-LPS) in presence or absence of
      butyrate for 4 and 24 h. The effects of butyrate on oxidative stress, p42/44 MAP
      kinase phosphorylation, p65-NF-kappaB activation and mucosal inflammation were
      investigated by real time PCR, western blot and confocal microscopy. Our results
      suggest that EC-LPS challenge induces a decrease in Gluthation-S-Transferase
      alpha (GSTA1/A2) mRNA levels, protein expression and catalytic activity; enhanced
      levels of ROS induced by EC-LPS challenge mediates p65-NF-kappaB activation and
      inflammatory response in Caco-2 cells and in CrD colonic mucosa. Furthermore
      butyrate treatment was seen to restore GSTA1/A2 mRNA levels, protein expression
      and catalytic activity and to control NF-kappaB activation, COX-2, ICAM-1 and the
      release of pro-inflammatory cytokine. In conclusion, butyrate rescues the redox
      machinery and controls the intracellular ROS balance thus switching off EC-LPS
      induced inflammatory response in intestinal epithelial cells and in CrD colonic
      mucosa.

PMID- 22412932
TI  - Buffalo, bush meat, and the zoonotic threat of brucellosis in Botswana.
AB  - BACKGROUND: Brucellosis is a zoonotic disease of global importance infecting
      humans, domestic animals, and wildlife. Little is known about the epidemiology
      and persistence of brucellosis in wildlife in Southern Africa, particularly in
      Botswana. METHODS: Archived wildlife samples from Botswana (1995-2000) were
      screened with the Rose Bengal Test (RBT) and fluorescence polarization assay
      (FPA) and included the African buffalo (247), bushbuck (1), eland (5), elephant
      (25), gemsbok (1), giraffe (9), hartebeest (12), impala (171), kudu (27), red
      lechwe (10), reedbuck (1), rhino (2), springbok (5), steenbok (2), warthog (24),
      waterbuck (1), wildebeest (33), honey badger (1), lion (43), and zebra (21).
      Human case data were extracted from government annual health reports (1974-2006).
      FINDINGS: Only buffalo (6%, 95% CI 3.04%-8.96%) and giraffe (11%, 95% CI 0
      38.43%) were confirmed seropositive on both tests. Seropositive buffalo were
      widely distributed across the buffalo range where cattle density was low. Human
      infections were reported in low numbers with most infections (46%) occurring in
      children (<14 years old) and no cases were reported among people working in the
      agricultural sector. CONCLUSIONS: Low seroprevalence of brucellosis in Botswana
      buffalo in a previous study in 1974 and again in this survey suggests an endemic
      status of the disease in this species. Buffalo, a preferred source of bush meat,
      is utilized both legally and illegally in Botswana. Household meat processing
      practices can provide widespread pathogen exposure risk to family members and the
      community, identifying an important source of zoonotic pathogen transmission
      potential. Although brucellosis may be controlled in livestock populations,
      public health officials need to be alert to the possibility of human infections
      arising from the use of bush meat. This study illustrates the need for a unified
      approach in infectious disease research that includes consideration of both
      domestic and wildlife sources of infection in determining public health risks
      from zoonotic disease invasions.

PMID- 22412933
TI  - Peripheral arterial and venous response to tilt test after a 60-day bedrest with
      and without countermeasures (ES-IBREP).
AB  - We quantified the impact of 60-day head-down bed rest (HDBR) with countermeasures
      on arterial and venous response to tilt. METHODS: Twenty-one males: 7 control
      (Con), 7 resistive vibration exercise (RVE) and 7 Chinese herb (Herb) were
      assessed. Subjects were identified as finisher (F) or non-finishers (NF) at the
      post-HDBR 20-min tilt test. The cerebral (MCA), femoral (FEM) arterial flow
      velocity and leg vascular resistance (FRI), the portal vein section (PV), the
      flow redistribution ratios (MCA/FEM; MCA/PV), the tibial (Tib), gastrocnemius
      (Gast), and saphenous (Saph) vein sections were measured by echography and
      Doppler ultrasonography. Arterial and venous parameters were measured at 3-min
      pre-tilt in the supine position, and at 1 min before the end of the tilt.
      RESULTS: At post-HDBR tilt, MCA decreased more compared with pre-HDBR tilt in the
      Con, RVE, and Herb groups, the MCA/FEM tended to decrease in the Con and Herb
      groups (not significant) but remained stable in the RVE gr. FRI dropped in the
      Con gr, but remained stable in the Herb gr and increased in the RVE gr. PV
      decreased less in the Con and Herb groups but remained unchanged in the RVE gr.
      MCA/PV decreased in the Con and Herb groups, but increased to a similar extent in
      the RVE gr. Gast section significantly increased more in the Con gr only, whereas
      Tib section increased more in the Con and Herb groups but not in the RVE gr. The
      percent change in Saph section was similar at pre- and post-HDBR tilt.
      CONCLUSION: In the Con gr, vasoconstriction was reduced in leg and splanchnic
      areas. RVE and Herb contributed to prevent the loss of vasoconstriction in both
      areas, but the effect of RVE was higher. RVE and Herb contributed to limit Gast
      distension whereas only RVE had a protective effect on the Tib.

PMID- 22412934
TI  - Reverse genetics of SARS-related coronavirus using vaccinia virus-based
      recombination.
AB  - Severe acute respiratory syndrome (SARS) is a zoonotic disease caused by SARS
      related coronavirus (SARS-CoV) that emerged in 2002 to become a global health
      concern. Although the original outbreak was controlled by classical public health
      measures, there is a real risk that another SARS-CoV could re-emerge from its
      natural reservoir, either in its original form or as a more virulent or
      pathogenic strain; in which case, the virus would be difficult to control in the
      absence of any effective antiviral drugs or vaccines. Using the well-studied SARS
      CoV isolate HKU-39849, we developed a vaccinia virus-based SARS-CoV reverse
      genetic system that is both robust and biosafe. The SARS-CoV genome was cloned in
      separate vaccinia virus vectors, (vSARS-CoV-5prime and vSARS-CoV-3prime) as two
      cDNAs that were subsequently ligated to create a genome-length SARS-CoV cDNA
      template for in vitro transcription of SARS-CoV infectious RNA transcripts.
      Transfection of the RNA transcripts into permissive cells led to the recovery of
      infectious virus (recSARS-CoV). Characterization of the plaques produced by
      recSARS-CoV showed that they were similar in size to the parental SARS-CoV
      isolate HKU-39849 but smaller than the SARS-CoV isolate Frankfurt-1. Comparative
      analysis of replication kinetics showed that the kinetics of recSARS-CoV
      replication are similar to those of SARS-CoV Frankfurt-1, although the titers of
      virus released into the culture supernatant are approximately 10-fold less. The
      reverse genetic system was finally used to generate a recSARS-CoV reporter virus
      expressing Renilla luciferase in order to facilitate the analysis of SARS-CoV
      gene expression in human dendritic cells (hDCs). In parallel, a Renilla
      luciferase gene was also inserted into the genome of human coronavirus 229E (HCoV
      229E). Using this approach, we demonstrate that, in contrast to HCoV-229E, SARS
      CoV is not able to mediate efficient heterologous gene expression in hDCs.

PMID- 22412935
TI  - Characterization and comparative analysis of small RNAs in three small RNA
      libraries of the brown planthopper (Nilaparvata lugens).
AB  - BACKGROUND: The brown planthopper (BPH), Nilaparvata lugens (Sta;l), which
      belongs to Homopteran, Delphacidae, is one of the most serious and destructive
      pests of rice. Feeding BPH with homologous dsRNA in vitro can lead to the death
      of BPH, which gives a valuable clue to the prevention and control of this pest,
      however, we know little about its small RNA world. METHODOLOGY/PRINCIPAL
      FINDINGS: Small RNA libraries for three developmental stages of BPH (CX-male
      adult, CC-female adult, CY-last instar female nymph) had been constructed and
      sequenced. It revealed a prolific small RNA world of BPH. We obtained a final
      list of 452 (CX), 430 (CC), and 381 (CY) conserved microRNAs (miRNAs),
      respectively, as well as a total of 71 new miRNAs in the three libraries. All the
      miRNAs had their own expression profiles in the three libraries. The phylogenic
      evolution of the miRNA families in BPH was consistent with other species. The new
      miRNA sequences demonstrated some base biases. CONCLUSION: Our study discovered a
      large number of small RNAs through deep sequencing of three small RNA libraries
      of BPH. Many animal-conserved miRNA families as well as some novel miRNAs have
      been detected in our libraries. This is the first achievement to discover the
      small RNA world of BPH. A lot of new valuable information about BPH small RNAs
      has been revealed which was helpful for studying insect molecular biology and
      insect resistant research.

PMID- 22412936
TI  - The 5' flanking region and intron1 of the bovine prion protein gene (PRNP) are
      responsible for negative feedback regulation of the prion protein.
AB  - Transcription factors regulate gene expression by controlling the transcription
      rate. Some genes can repress their own expression to prevent over production of
      the corresponding protein, although the mechanism and significance of this
      negative feedback regulation remains unclear. In the present study, we describe
      negative feedback regulation of the bovine prion protein (PrP) gene PRNP in
      Japanese Black cattle. The PrP-expressing plasmid pEF-boPrP and luciferase
      expressing plasmids containing the partial promoter fragment of PRNP
      incorporating naturally occurring single-nucleotide or insertion/deletion
      polymorphisms were transfected into N2a cells. Transfection of pEF-boPrP induced
      PrP overexpression and decreased the promoter activity of PRNP in the wild-type
      haplotype (23-bp Del, 12-bp Del, and -47C). Reporter gene assays further
      demonstrated that the 12- and 23-bp Ins/Del polymorphisms, which are thought to
      be associated with Sp1 (Specific protein 1) and RP58 (Repressor Protein with a
      predicted molecular mass of 58 kDa), in intron1 and the upstream region,
      respectively, and an additional polymorphism (-47C->A) in the Sp1-binding site
      responded differently to PrP overexpression. With the -47C SNP, the presence of
      the Del in either the 23-bp Ins/Del or the 12-bp Ins/Del allele was essential for
      the negative feedback caused by PrP overexpression. Furthermore, deletion mutants
      derived from the wild-type haplotype showed that nucleotides -315 to +2526, which
      include the 5'-flanking region and exon1, were essential for the response. These
      results indicate that certain negative feedback response elements are located in
      these sequences, suggesting that regulation by transcription factors such as Sp1
      and RP58 may contribute to the negative feedback mechanism of PRNP.

PMID- 22412937
TI  - SPECT/CT imaging of hNIS-expression after intravenous delivery of an oncolytic
      adenovirus and 131I.
AB  - Oncolytic adenoviruses can be engineered for better tumor selectivity, gene
      delivery and be armed for imaging and concentrating radionuclides into tumors for
      synergistic oncolysis. We constructed Ad5/3-hTERT-hNIS where replication is
      controlled by hTERT-promoter. Ad5/3-hTERT-hNIS expresses hNIS for imaging of
      transgene expression and for treatment of infected tumors by radioiodine. Ad5/3
      hTERT-hNIS efficiently killed prostate cancer cells and induced iodine uptake in
      vitro and in vivo after intratumoral virus administration. Survival of mice
      treated with intravenous Ad5/3-hTERT-hNIS significantly prolonged survival over
      mock or radioiodine only but the combination of virus with radioiodine was not
      more effective than virus alone. Temporal and spatial changes in hNIS-expression
      during therapy were detected with SPECT, demonstrating feasibility of evaluation
      of the combination therapy with hNIS-expressing adenoviruses and radioiodide.

PMID- 22412938
TI  - Three-dimensional microscopy characterization of death receptor 5 expression by
      over-activated human primary CD4+ T cells and apoptosis.
AB  - Activation-induced cell death is a natural process that prevents tissue damages
      from over-activated immune cells. TNF-Related apoptosis ligand (TRAIL), a TNF
      family member, induces apoptosis of infected and tumor cells by binding to one of
      its two death receptors, DR4 or DR5. TRAIL was reported to be secreted by
      phytohemagglutinin (PHA)-stimulated CD4(+) T cells in microvesicles.We
      investigate here TRAIL and DR5 regulation by activated primary CD4(+) T cells and
      its consequence on cell death. We observed that PHA induced CD4(+) T cell
      apoptosis in a dose-dependent manner. Thus, we investigated molecules involved in
      PHA-mediated cell death and demonstrated that TRAIL and DR5 were over-expressed
      on the plasma membrane of PHA-stimulated CD4(+) T cells. Surprisingly, DR5 was
      constitutively expressed in naive CD4(+) T cells at messenger RNA (mRNA) and
      protein levels. Thus, using 3 dimensional microscopy and intracellular staining
      assays, we show that DR5 is constitutively expressed in CD4(+) T cells and is pre
      stocked in the cytoplasm. When cells are stimulated by PHA, DR5 is relocalized
      from cytoplasm to plasma membrane. Small interference RNA (siRNA) and blocking
      antibody assays demonstrate that TRAIL/DR5 interaction is mainly responsible for
      PHA-mediated CD4(+) T cell apoptosis. Thus, membrane DR5 expression leading to
      TRAIL-mediated apoptosis may represent one of the pathways responsible for
      eradication of over-activated CD4(+) T cells during immune responses.

PMID- 22412939
TI  - Test characteristics of urinary lipoarabinomannan and predictors of mortality
      among hospitalized HIV-infected tuberculosis suspects in Tanzania.
AB  - BACKGROUND: Tuberculosis is the most common cause of death among patients with
      HIV infection living in tuberculosis endemic countries, but many cases are not
      diagnosed pre-mortem. We assessed the test characteristics of urinary
      lipoarabinomannan (LAM) and predictors of mortality among HIV-associated
      tuberculosis suspects in Tanzania. METHODS: We prospectively enrolled
      hospitalized HIV-infected patients in Dar es Salaam, with >=2 weeks of cough or
      fever, or weight loss. Subjects gave 2 mLs of urine to test for LAM using a
      commercially available ELISA, >=2 sputum specimens for concentrated AFB smear and
      solid media culture, and 40 mLs of blood for culture. RESULTS: Among 212
      evaluable subjects, 143 (68%) were female; mean age was 36 years; and the median
      CD4 count 86 cells/mm(3). 69 subjects (33%) had culture confirmation of
      tuberculosis and 65 (31%) were LAM positive. For 69 cases of sputum or blood
      culture-confirmed tuberculosis, LAM sensitivity was 65% and specificity 86%
      compared to 36% and 98% for sputum smear. LAM test characteristics were not
      different in patients with bacteremia but showed higher sensitivity and lower
      specificity with decreasing CD4 cell count. Two month mortality was 64 (53%) of
      121 with outcomes available. In multivariate analysis there was significant
      association of mortality with absence of anti-retroviral therapy (p = 0.004) and
      a trend toward association with a positive urine LAM (p = 0.16). Among culture
      negative patients mortality was 9 (75%) of 12 in LAM positive patients and 27
      (38%) of 71 in LAM negative patients (p = 0.02). CONCLUSIONS: Urine LAM is more
      sensitive than sputum smear and has utility for the rapid diagnosis of culture
      confirmed tuberculosis in this high-risk population. Mortality data raise the
      possibility that urine LAM may also be a marker for culture-negative
      tuberculosis.

PMID- 22412940
TI  - Analysis of human accelerated DNA regions using archaic hominin genomes.
AB  - Several previous comparisons of the human genome with other primate and
      vertebrate genomes identified genomic regions that are highly conserved in
      vertebrate evolution but fast-evolving on the human lineage. These human
      accelerated regions (HARs) may be regions of past adaptive evolution in humans.
      Alternatively, they may be the result of non-adaptive processes, such as biased
      gene conversion. We captured and sequenced DNA from a collection of previously
      published HARs using DNA from an Iberian Neandertal. Combining these new data
      with shotgun sequence from the Neandertal and Denisova draft genomes, we
      determine at least one archaic hominin allele for 84% of all positions within
      HARs. We find that 8% of HAR substitutions are not observed in the archaic
      hominins and are thus recent in the sense that the derived allele had not come to
      fixation in the common ancestor of modern humans and archaic hominins. Further,
      we find that recent substitutions in HARs tend to have come to fixation faster
      than substitutions elsewhere in the genome and that substitutions in HARs tend to
      cluster in time, consistent with an episodic rather than a clock-like process
      underlying HAR evolution. Our catalog of sequence changes in HARs will help
      prioritize them for functional studies of genomic elements potentially
      responsible for modern human adaptations.

PMID- 22412941
TI  - COMP-angiopoietin-1 recovers molecular biomarkers of neuropathy and improves
      vascularisation in sciatic nerve of ob/ob mice.
AB  - BACKGROUND: Leptin-deficient ob/ob mice are a model of type 2 diabetes induced
      peripheral neuropathy. Ob/ob mice exhibit obesity, insulin resistance,
      hyperglycaemia, and alterations of peripheral nerve fibres and endoneural
      microvessels. Here we test the hypothesis that cartilage oligomeric matrix
      protein (COMP)-Ang-1, a soluble and stabile form of Ang-1 which promotes
      angiogenesis and nerve growth, improves regeneration of nerve fibres and
      endoneural microvessels in ob/ob mice. METHODS AND FINDINGS: COMP-Ang-1 (100
      ng/ml) or NaCl were intraperitoneally (i.p.) injected into male (N = 184), 3
      month old, ob/ob or ob/+ mice for 7 and 21 days. We measured expression of Nf68,
      GAP43, Cx32, Cx26, Cx43, and TNFalpha in sciatic nerves using Western blot
      analysis. To investigate the inflammation in sciatic nerves, numbers of
      macrophages and T-cells were counted after immunofluorescence staining. In
      ultrathin section, number of myelinated/non-mylinated nerve fibers, g-ratio, the
      thickness of Schwann cell basal lamina and microvessel endothelium were
      investigated. Endoneural microvessels were reconstructed with intracardial FITC
      injection. Treatment with COMP-Ang-1 over 21 days significantly reduced fasting
      blood glucose and plasma cholesterol concentrations compared to saline treated
      ob/ob mice. In addition, COMP-Ang-1 treatment: 1) up-regulated expression of Nf68
      and GAP43; 2) improved expression of gap junction proteins including connexin 32
      and 26; 3) suppressed the expression of TNFalpha and Cx43 and 4) led to decreased
      macrophage and T-cell infiltration in sciatic nerve of ob/ob mice. The
      significant changes of sciatic nerve ultrastructure were not observed after 21
      day long COMP-Ang-1 treatment. COMP-Ang-1 treated ob/ob mice displayed
      regeneration of small-diameter endoneural microvessels. Effects of COMP-Ang-1
      corresponded to increased phosphorylation of Akt and p38 MAPK upon Tie-2
      receptor. CONCLUSIONS: COMP-Ang-1 recovers molecular biomarkers of neuropathy,
      promotes angiogenesis and suppresses inflammation in sciatic nerves of ob/ob mice
      suggesting COMP-Ang-1 as novel treatment option to improve morphologic and
      protein expression changes associated with diabetic neuropathy.

PMID- 22412942
TI  - The MYST-containing protein Chameau is required for proper sensory organ
      specification during Drosophila thorax morphogenesis.
AB  - The adult thorax of Drosophila melanogaster is covered by a stereotyped pattern
      of mechanosensory bristles called macrochaetes. Here, we report that the MYST
      containing protein Chameau (Chm) contributes to the establishment of this pattern
      in the most dorsal part of the thorax. Chm mutant pupae present extra
      dorsocentral (DC) and scutellar (SC) macrochaetes, but a normal number of the
      other macrochaetes. We provide evidences that chm restricts the singling out of
      sensory organ precursors from proneural clusters and genetically interacts with
      transcriptional regulators involved in the regulation of achaete and scute in the
      DC and SC proneural cluster. This function of chm likely relies on chromatin
      structure regulation since a protein with a mutation in the conserved catalytic
      site fails to rescue the formation of supernumerary DC and SC bristles in chm
      mutant flies. This is further supported by the finding that mutations in genes
      encoding chromatin modifiers and remodeling factors, including Polycomb group
      (PcG) and Trithorax group (TrxG) members, dominantly modulate the penetrance of
      chm extra bristle phenotype. These data support a critical role for chromatin
      structure modulation in the establishment of the stereotyped sensory bristle
      pattern in the fly thorax.

PMID- 22412943
TI  - An economic evaluation of preclinical testing strategies compared to the
      compulsory scrapie flock scheme in the control of classical scrapie.
AB  - Cost-benefit is rarely combined with nonlinear dynamic models when evaluating
      control options for infectious diseases. The current strategy for scrapie in
      Great Britain requires that all genetically susceptible livestock in affected
      flocks be culled (Compulsory Scrapie Flock Scheme or CSFS). However, this results
      in the removal of many healthy sheep, and a recently developed pre-clinical test
      for scrapie now offers a strategy based on disease detection. We explore the
      flock level cost-effectiveness of scrapie control using a deterministic
      transmission model and industry estimates of costs associated with genotype
      testing, pre-clinical tests and the value of a sheep culled. Benefit was measured
      in terms of the reduction in the number of infected sheep sold on, compared to a
      baseline strategy of doing nothing, using Incremental Cost Effectiveness analysis
      to compare across strategies. As market data was not available for pre-clinical
      testing, a threshold analysis was used to set a unit-cost giving equal costs for
      CSFS and multiple pre-clinical testing (MT, one test each year for three
      consecutive years). Assuming a 40% within-flock proportion of susceptible
      genotypes and a test sensitivity of 90%, a single test (ST) was cheaper but less
      effective than either the CSFS or MT strategies (30 infected-sales-averted over
      the lifetime of the average epidemic). The MT strategy was slightly less
      effective than the CSFS and would be a dominated strategy unless preclinical
      testing was cheaper than the threshold price of L6.28, but may be appropriate for
      flocks with particularly valuable livestock. Though the ST is not currently
      recommended, the proportion of susceptible genotypes in the national flock is
      likely to continue to decrease; this may eventually make it a cost-effective
      alternative to the MT or CSFS.

PMID- 22412944
TI  - Chemotherapeutic sensitization of leptomycin B resistant lung cancer cells by
      pretreatment with doxorubicin.
AB  - The development of novel targeted therapies has become an important research
      focus for lung cancer treatment. Our previous study has shown leptomycin B (LMB)
      significantly inhibited proliferation of lung cancer cells; however, p53 wild
      type lung cancer cells were resistant to LMB. Therefore, the objective of this
      study was to develop and evaluate a novel therapeutic strategy to sensitize LMB
      resistant lung cancer cells by combining LMB and doxorubicin (DOX). Among the
      different treatment regimens, pretreatment with DOX (pre-DOX) and subsequent
      treatment with LMB to A549 cells significantly decreased the 50% inhibitory
      concentration (IC50) as compared to that of LMB alone (4.4 nM vs. 10.6 nM,
      P<0.05). Analysis of cell cycle and apoptosis by flow cytometry further confirmed
      the cytotoxic data. To investigate molecular mechanisms for this drug combination
      effects, p53 pathways were analyzed by Western blot, and nuclear proteome was
      evaluated by two dimensional-difference gel electrophoresis (2D-DIGE) and mass
      spectrometry. In comparison with control groups, the levels of p53, phospho-p53
      (ser15), and p21 proteins were significantly increased while phospho-p53 (Thr55)
      and survivin were significantly decreased after treatments of pre-DOX and LMB
      (P<0.05). The 2D-DIGE/MS analysis identified that sequestosome 1 (SQSTM1/p62) had
      a significant increase in pre-DOX and LMB-treated cells (P<0.05). In conclusion,
      our results suggest that drug-resistant lung cancer cells with p53 wild type
      could be sensitized to cell death by scheduled combination treatment of DOX and
      LMB through activating and restoring p53 as well as potentially other signaling
      pathway(s) involving sequestosome 1.

PMID- 22412945
TI  - Lessons learned developing a diagnostic tool for HIV-associated dementia feasible
      to implement in resource-limited settings: pilot testing in Kenya.
AB  - OBJECTIVE: To conduct a preliminary evaluation of the utility and reliability of
      a diagnostic tool for HIV-associated dementia (HAD) for use by primary health
      care workers (HCW) which would be feasible to implement in resource-limited
      settings. BACKGROUND: In resource-limited settings, HAD is an indication for anti
      retroviral therapy regardless of CD4 T-cell count. Anti-retroviral therapy, the
      treatment for HAD, is now increasingly available in resource-limited settings.
      Nonetheless, HAD remains under-diagnosed likely because of limited clinical
      expertise and availability of diagnostic tests. Thus, a simple diagnostic tool
      which is practical to implement in resource-limited settings is an urgent need.
      METHODS: A convenience sample of 30 HIV-infected outpatients was enrolled in
      Western Kenya. We assessed the sensitivity and specificity of a diagnostic tool
      for HAD as administered by a primary HCW. This was compared to an expert clinical
      assessment which included examination by a physician, neuropsychological testing,
      and in selected cases, brain imaging. Agreement between HCW and an expert
      examiner on certain tool components was measured using Kappa statistic. RESULTS:
      The sample was 57% male, mean age was 38.6 years, mean CD4 T-cell count was 323
      cells/uL, and 54% had less than a secondary school education. Six (20%) of the
      subjects were diagnosed with HAD by expert clinical assessment. The diagnostic
      tool was 63% sensitive and 67% specific for HAD. Agreement between HCW and expert
      examiners was poor for many individual items of the diagnostic tool (K = .03
      .65). This diagnostic tool had moderate sensitivity and specificity for HAD.
      However, reliability was poor, suggesting that substantial training and formal
      evaluations of training adequacy will be critical to enable HCW to reliably
      administer a brief diagnostic tool for HAD.

PMID- 22412946
TI  - Intermittent preventive treatment of malaria in children: a qualitative study of
      community perceptions and recommendations in Burkina Faso and Mali.
AB  - BACKGROUND: Intermittent preventive treatment of malaria in children (IPTc) is a
      highly efficacious method of malaria control where malaria transmission is highly
      seasonal. However, no studies published to date have examined community
      perceptions of IPTc. METHODS: A qualitative study was undertaken in parallel with
      a double-blind, placebo-controlled, randomized trial of IPTc conducted in Mali
      and Burkina Faso in 2008-2009 to assess community perceptions of and
      recommendations for IPTc. Caregivers and community health workers (CHWs) were
      purposively sampled. Seventy-two in-depth individual interviews and 23 focus
      group discussions were conducted. FINDINGS: Widespread perceptions of health
      benefits for children led to enthusiasm for the trial and for IPTc specifically.
      Trust in and respect for those providing the tablets and a sense of obligation to
      the community to participate in sanctioned activities favoured initial adoption.
      IPTc fits in well with existing understandings of childhood illness. Participants
      did not express concerns about the specific drugs used for IPTc or about
      providing tablets to children without symptoms of malaria. There was no evidence
      that IPTc was perceived as a substitute for bed net usage, nor did it inhibit
      care seeking. Participants recommended that distribution be "closer to the
      population", but expressed concern over caregivers' ability to administer tablets
      at home. CONCLUSIONS: The trial context mediated perceptions of IPTc.
      Nonetheless, the results indicate that community perceptions of IPTc in the
      settings studied were largely favourable and that the delivery strategy rather
      than the tablets themselves presented the main areas of concern for caregivers
      and CHWs. The study identifies a number of key questions to consider in planning
      an IPTc distribution strategy. Single-dose formulations could increase the
      success of IPTc implementation, as could integration of IPTc within a package of
      activities, such as bed net distribution and free curative care, for which demand
      is already high.

PMID- 22412947
TI  - Testing human sperm chemotaxis: how to detect biased motion in population assays.
AB  - Biased motion of motile cells in a concentration gradient of a chemoattractant is
      frequently studied on the population level. This approach has been particularly
      employed in human sperm chemotactic assays, where the fraction of responsive
      cells is low and detection of biased motion depends on subtle differences. In
      these assays, statistical measures such as population odds ratios of swimming
      directions can be employed to infer chemotactic performance. Here, we report on
      an improved method to assess statistical significance of experimentally
      determined odds ratios and discuss the strong impact of data correlations that
      arise from the directional persistence of sperm swimming.

PMID- 22412948
TI  - bantam is required for optic lobe development and glial cell proliferation.
AB  - microRNAs (miRNAs) are small, conserved, non-coding RNAs that contribute to the
      control of many different cellular processes, including cell fate specification
      and growth control. Drosophila bantam, a conserved miRNA, is involved in several
      functions, such as stimulating proliferation and inhibiting apoptosis in the wing
      disc. Here, we reported the detailed expression pattern of bantam in the
      developing optic lobe, and demonstrated a new, essential role in promoting
      proliferation of mitotic cells in the optic lobe, including stem cells and
      differentiated glial cells. Changes in bantam levels autonomously affected glial
      cell number and distribution, and non-autonomously affected photoreceptor neuron
      axon projection patterns. Furthermore, we showed that bantam promotes the
      proliferation of mitotically active glial cells and affects their distribution,
      largely through down regulation of the T-box transcription factor, optomotor
      blind (omb, Flybase, bifid). Expression of omb can rescue the bantam phenotype,
      and restore the normal glial cell number and proper glial cell positioning in
      most Drosophila brains. These results suggest that bantam is critical for
      maintaining the stem cell pools in the outer proliferation center and glial
      precursor cell regions of the optic lobe, and that its expression in glial cells
      is crucial for their proliferation and distribution.

PMID- 22412949
TI  - Different infective forms trigger distinct immune response in experimental Chagas
      disease.
AB  - Although metacyclic and blood trypomastigotes are completely functional in
      relation to parasite-host interaction and/or target cell invasion, they differ in
      the molecules present on the surface. Thus, aspects related to the variability
      that the forms of T. cruzi interacts with host cells may lead to fundamental
      implications on the immune response against this parasite and, consequently, the
      clinical evolution of Chagas disease. We have shown that BT infected mice
      presented higher levels of parasitemia during all the acute phase of infection.
      Moreover, the infection with either MT or BT forms resulted in increased levels
      of total leukocytes, monocytes and lymphocytes, specifically later for MT and
      earlier for BT. The infection with BT forms presented earlier production of
      proinflammatory cytokine TNF-alpha and later of IFN-gamma by both T cells
      subpopulations. This event was accompanied by an early cardiac inflammation with
      an exacerbation of this process at the end of the acute phase. On the other hand,
      infection with MT forms result in an early production of IFN-gamma, with
      subsequent control in the production of this cytokine by IL-10, which provided to
      these animals an immunomodulatory profile in the end of the acute phase. These
      results are in agreement with what was found for cardiac inflammation where
      animals infected with MT forms showed intense cardiac inflammation later at
      infection, with a decrease in the same at the end of this phase. In summary, our
      findings emphasize the importance of taking into account the inoculums source of
      T. cruzi, since vectorial or transfusional routes of T. cruzi infection may
      trigger distinct parasite-host interactions during the acute phase that may
      influence relevant biological aspects of chronic Chagas disease.

PMID- 22412950
TI  - Induction of overt menstruation in intact mice.
AB  - The complex tissue remodeling process of menstruation is experienced by humans
      and some primates, whereas most placental mammals, including mice, go through an
      estrous cycle. How menstruation and the underlying mechanisms evolved is still
      unknown. Here we demonstrate that the process of menstruation is not just species
      specific but also depends on factors which can be induced experimentally. In
      intact female mice endogenous progesterone levels were raised by the induction of
      pseudopregnancy. Following an intrauterine oil injection, the decidualization of
      the endometrium was reliably induced as a prerequisite for menstruation. The
      natural drop of endogenous progesterone led to spontaneous breakdown of
      endometrial tissue within an average of 3 days post induction of decidualization.
      Interestingly, morphological changes such as breakdown and repair of the
      endometrial layer occurred in parallel in the same uterine horn. Most
      importantly, endometrial breakdown was accompanied by vaginally visible (overt)
      bleeding and flushing out of shed tissue comparable to human menstruation. Real
      time PCR data clearly showed temporal changes in the expression of multiple
      factors participating in inflammation, angiogenesis, tissue modulation,
      proliferation, and apoptosis, as has been described for human menstruating
      endometrium. In conclusion, human menstruation can be mimicked in terms of
      extravaginally visible bleeding, tissue remodeling, and gene regulation in
      naturally non-menstruating species such as intact female mice without the need
      for an exogenous hormone supply.

PMID- 22412951
TI  - Comparison of nasal and bronchial epithelial cells obtained from patients with
      COPD.
AB  - For in vitro studies of airway pathophysiology, primary epithelial cells have
      many advantages over immortalised cell lines. Nasal epithelial cells are easier
      to obtain than bronchial epithelial cells and can be used as an alternative for
      in vitro studies. Our objective was to compare nasal and bronchial epithelial
      cells from subjects with COPD to establish if these cells respond similarly to
      pro-inflammatory stimuli. Cell cultures from paired nasal and bronchial brushings
      (21 subjects) were incubated with cigarette smoke extract (CSE) prior to
      stimulation with Pseudomonas aeruginosa lipopolysaccharide. IL-6 and IL-8 were
      measured by ELISA and Toll-like receptor 4 (TLR-4) message and expression by RT
      PCR and FACS respectively. IL-8 release correlated significantly between the two
      cell types. IL-6 secretion was significantly less from bronchial compared to
      nasal epithelial cells and secreted concentrations did not correlate. A 4 h CSE
      incubation was immunosuppressive for both nasal and bronchial cells, however
      prolonged incubation for 24 h was pro-inflammatory solely for the nasal cells.
      CSE reduced TLR-4 expression in bronchial cells only after 24 h, and was without
      effect on mRNA expression. In subjects with COPD, nasal epithelial cells cannot
      substitute for in vitro bronchial epithelial cells in airway inflammation
      studies.

PMID- 22412952
TI  - Bone surface mapping method.
AB  - Bone shape is an important factor to determine the bone's structural function.
      For the asymmetrically shaped and anisotropically distributed bone in vivo, a
      surface mapping method is proposed on the bases of its geometric transformation
      invariance and its uniqueness of the principal axes of inertia. Using spiral CT
      scanning, we can make precise measurements to bone in vivo. The coordinate
      transformations lead to the principal axes of inertia, with which the prime
      meridian and the contour can be set. Methods such as tomographic reconstruction
      and boundary development are employed so that the surface of bone in vivo can be
      mapped. Experimental results show that the surface mapping method can reflect the
      shape features and help study the surface changes of bone in vivo. This method
      can be applied to research into the surface characteristics and changes of organ,
      tissue or cell whenever its digitalized surface is obtained.

PMID- 22412953
TI  - Scalable in situ hybridization on tissue arrays for validation of novel cancer
      and tissue-specific biomarkers.
AB  - Tissue localization of gene expression is increasingly important for accurate
      interpretation of large scale datasets from expression and mutational analyses.
      To this end, we have (1) developed a robust and scalable procedure for generation
      of mRNA hybridization probes, providing >95% first-pass success rate in probe
      generation to any human target gene and (2) adopted an automated staining
      procedure for analyses of formalin-fixed paraffin-embedded tissues and tissue
      microarrays. The in situ mRNA and protein expression patterns for genes with
      known as well as unknown tissue expression patterns were analyzed in normal and
      malignant tissues to assess procedure specificity and whether in situ
      hybridization can be used for validating novel antibodies. We demonstrate
      concordance between in situ transcript and protein expression patterns of the
      well-known pathology biomarkers KRT17, CHGA, MKI67, PECAM1 and VIL1, and provide
      independent validation for novel antibodies to the biomarkers BRD1, EZH2, JUP and
      SATB2. The present study provides a foundation for comprehensive in situ gene set
      or transcriptome analyses of human normal and tumor tissues.

PMID- 22412955
TI  - I undervalue you but I need you: the dissociation of attitude and memory toward
      in-group members.
AB  - In the present study, the in-group bias or in-group derogation among Mainland
      Chinese was investigated through a rating task and a recognition test. In two
      experiments,participants from two universities with similar ranks rated novel
      faces or names and then had a recognition test. Half of the faces or names were
      labeled as participants' own university and the other half were labeled as their
      counterpart. Results showed that, for either faces or names, rating scores for
      out-group members were consistently higher than those for in-group members,
      whereas the recognition accuracy showed just the opposite. These results
      indicated that the attitude and memory for group-relevant information might be
      dissociated among Mainland Chinese.

PMID- 22412954
TI  - The influence of cis-regulatory elements on DNA methylation fidelity.
AB  - It is now established that, as compared to normal cells, the cancer cell genome
      has an overall inverse distribution of DNA methylation ("methylome"), i.e.,
      predominant hypomethylation and localized hypermethylation, within "CpG islands"
      (CGIs). Moreover, although cancer cells have reduced methylation "fidelity" and
      genomic instability, accurate maintenance of aberrant methylomes that underlie
      malignant phenotypes remains necessary. However, the mechanism(s) of cancer
      methylome maintenance remains largely unknown. Here, we assessed CGI methylation
      patterns propagated over 1, 3, and 5 divisions of A2780 ovarian cancer cells,
      concurrent with exposure to the DNA cross-linking chemotherapeutic cisplatin, and
      observed cell generation-successive increases in total hyper- and hypo-methylated
      CGIs. Empirical bayesian modeling revealed five distinct modes of methylation
      propagation: (1) heritable (i.e., unchanged) high-methylation (1186 probe loci in
      CGI microarray); (2) heritable (i.e., unchanged) low-methylation (286 loci); (3)
      stochastic hypermethylation (i.e., progressively increased, 243 loci); (4)
      stochastic hypomethylation (i.e., progressively decreased, 247 loci); and (5)
      considerable "random" methylation (582 loci). These results support a "stochastic
      model" of DNA methylation equilibrium deriving from the efficiency of two
      distinct processes, methylation maintenance and de novo methylation. A role for
      cis-regulatory elements in methylation fidelity was also demonstrated by highly
      significant (p<2.2*10(-5)) enrichment of transcription factor binding sites in
      CGI probe loci showing heritably high (118 elements) and low (47 elements)
      methylation, and also in loci demonstrating stochastic hyper-(30 elements) and
      hypo-(31 elements) methylation. Notably, loci having "random" methylation
      heritability displayed nearly no enrichment. These results demonstrate an
      influence of cis-regulatory elements on the nonrandom propagation of both
      strictly heritable and stochastically heritable CGIs.

PMID- 22412956
TI  - DNA barcoding and microsatellites help species delimitation and hybrid
      identification in endangered galaxiid fishes.
AB  - The conservation of data deficient species is often hampered by inaccurate
      species delimitation. The galaxiid fishes Aplochiton zebra and Aplochiton
      taeniatus are endemic to Patagonia (and for A. zebra the Falkland Islands), where
      they are threatened by invasive salmonids. Conservation of Aplochiton is
      complicated because species identification is hampered by the presence of
      resident as well as migratory ecotypes that may confound morphological
      discrimination. We used DNA barcoding (COI, cytochrome b) and a new developed set
      of microsatellite markers to investigate the relationships between A. zebra and
      A. taeniatus and to assess their distributions and relative abundances in Chilean
      Patagonia and the Falkland Islands. Results from both DNA markers were 100%
      congruent and revealed that phenotypic misidentification was widespread, size
      dependent, and highly asymmetric. While all the genetically classified A. zebra
      were correctly identified as such, 74% of A. taeniatus were incorrectly
      identified as A. zebra, the former species being more widespread than previously
      thought. Our results reveal, for the first time, the presence in sympatry of both
      species, not only in Chilean Patagonia, but also in the Falkland Islands, where
      A. taeniatus had not been previously described. We also found evidence of
      asymmetric hybridisation between female A. taeniatus and male A. zebra in areas
      where invasive salmonids have become widespread. Given the potential consequences
      that species misidentification and hybridisation can have for the conservation of
      these endangered species, we advocate the use of molecular markers in order to
      reduce epistemic uncertainty.

PMID- 22412957
TI  - Deep sequencing analyses of low density microbial communities: working at the
      boundary of accurate microbiota detection.
AB  - INTRODUCTION: Accurate analyses of microbiota composition of low-density
      communities (10(3)-10(4) bacteria/sample) can be challenging. Background DNA from
      chemicals and consumables, extraction biases as well as differences in PCR
      efficiency can significantly interfere with microbiota assessment. This study was
      aiming to establish protocols for accurate microbiota analysis at low microbial
      density. METHODS: To examine possible effects of bacterial density on microbiota
      analyses we compared microbiota profiles of serial diluted saliva and low (nares,
      nasopharynx) and high-density (oropharynx) upper airway communities in four
      healthy individuals. DNA was extracted with four different extraction methods
      (Epicentre Masterpure, Qiagen DNeasy, Mobio Powersoil and a phenol bead-beating
      protocol combined with Agowa-Mag-mini). Bacterial DNA recovery was analysed by
      16S qPCR and microbiota profiles through GS-FLX-Titanium-Sequencing of 16S rRNA
      gene amplicons spanning the V5-V7 regions. RESULTS: Lower template concentrations
      significantly impacted microbiota profiling results. With higher dilutions, low
      abundant species were overrepresented. In samples of <10(5) bacteria per ml, e.g.
      DNA <1 pg/ul, microbiota profiling deviated from the original sample and other
      dilutions showing a significant increase in the taxa Proteobacteria and decrease
      in Bacteroidetes. In similar low density samples, DNA extraction method
      determined if DNA levels were below or above 1 pg/ul and, together with lysis
      preferences per method, had profound impact on microbiota analyses in both
      relative abundance as well as representation of species. CONCLUSION: This study
      aimed to interpret microbiota analyses of low-density communities. Bacterial
      density seemed to interfere with microbiota analyses at < than 10(6) bacteria per
      ml or DNA <1 pg/ul. We therefore recommend this threshold for working with low
      density materials. This study underlines that bias reduction is crucial for
      adequate profiling of especially low-density bacterial communities.

PMID- 22412958
TI  - Time course and pattern of metastasis of cutaneous melanoma differ between men
      and women.
AB  - BACKGROUND: This study identified sex differences in progression of cutaneous
      melanoma. METHODOLOGY/PRINCIPAL FINDINGS: Of 7,338 patients who were diagnosed as
      an invasive primary CM without clinically detectable metastases from 1976 to 2008
      at the University of Tuebingen in Germany, 1,078 developed subsequent metastases
      during follow up. The metastatic pathways were defined in these patients and
      analyzed using the Kaplan-Meier method. Multivariate survival analysis was
      performed using Cox modeling. In 18.7% of men and 29.2% of women (P<0.001) the
      first metastasis following diagnosis of primary tumor was locoregional as
      satellite/in-transit metastasis. The majority of men (54.0%) and women (47.6%, P
      = 0.035) exhibited direct regional lymph node metastasis. Direct distant
      metastasis from the stage of the primary tumor was observed in 27.3% of men and
      23.2% of women (P = 0.13). Site of first metastasis was the most important
      prognostic factor of survival after recurrence in multivariate analysis (HR:1.3;
      95% CI: 1.0-1.6 for metastasis to the regional lymph nodes vs. satellite/in
      transit recurrence, and HR:5.5; 95% CI: 4.2-7.1 for distant metastasis vs.
      satellite/in-transit recurrence, P<0.001). Median time to distant metastasis was
      40.5 months (IQR, 58.75) in women and 33 months (IQR, 44.25) in men (P = 0.002).
      Five-year survival after distant recurrence probability was 5.2% (95% CI: 1.4
      2.5) for men compared with 15.3% (95% CI: 11.1-19.5; P = 0.008) for women.
      CONCLUSIONS/SIGNIFICANCE: Both, the pattern of metastatic spread with more
      locoregional metastasis in women, and the time course with retracted metastasis
      in women contributed to the more favorable outcome of women. Furthermore, the
      total rate of metastasis is increased in men. Interestingly, there is also a much
      more favorable long term survival of women after development of distant
      metastasis. It remains a matter of debate and of future research, whether
      hormonal or immunologic factors may be responsible for these sex differences.

PMID- 22412959
TI  - The use of EST expression matrixes for the quality control of gene expression
      data.
AB  - EST expression profiling provides an attractive tool for studying differential
      gene expression, but cDNA libraries' origins and EST data quality are not always
      known or reported. Libraries may originate from pooled or mixed tissues; EST
      clustering, EST counts, library annotations and analysis algorithms may contain
      errors. Traditional data analysis methods, including research into tissue
      specific gene expression, assume EST counts to be correct and libraries to be
      correctly annotated, which is not always the case. Therefore, a method capable of
      assessing the quality of expression data based on that data alone would be
      invaluable for assessing the quality of EST data and determining their
      suitability for mRNA expression analysis. Here we report an approach to the
      selection of a small generic subset of 244 UniGene clusters suitable for
      identification of the tissue of origin for EST libraries and quality control of
      the expression data using EST expression information alone. We created a small
      expression matrix of UniGene IDs using two rounds of selection followed by two
      rounds of optimisation. Our selection procedures differ from traditional
      approaches to finding "tissue-specific" genes and our matrix yields consistency
      high positive correlation values for libraries with confirmed tissues of origin
      and can be applied for tissue typing and quality control of libraries as small as
      just a few hundred total ESTs. Furthermore, we can pick up tissue correlations
      between related tissues e.g. brain and peripheral nervous tissue, heart and
      muscle tissues and identify tissue origins for a few libraries of uncharacterised
      tissue identity. It was possible to confirm tissue identity for some libraries
      which have been derived from cancer tissues or have been normalised. Tissue
      matching is affected strongly by cancer progression or library normalisation and
      our approach may potentially be applied for elucidating the stage of
      normalisation in normalised libraries or for cancer staging.

PMID- 22412960
TI  - Leptin resistance in vagal afferent neurons inhibits cholecystokinin signaling
      and satiation in diet induced obese rats.
AB  - BACKGROUND AND AIMS: The gastrointestinal hormone cholecystokinin (CCK) plays an
      important role in regulating meal size and duration by activating CCK1 receptors
      on vagal afferent neurons (VAN). Leptin enhances CCK signaling in VAN via an
      early growth response 1 (EGR1) dependent pathway thereby increasing their
      sensitivity to CCK. In response to a chronic ingestion of a high fat diet, VAN
      develop leptin resistance and the satiating effects of CCK are reduced. We tested
      the hypothesis that leptin resistance in VAN is responsible for reducing CCK
      signaling and satiation. RESULTS: Lean Zucker rats sensitive to leptin signaling,
      significantly reduced their food intake following administration of CCK8S (0.22
      nmol/kg, i.p.), while obese Zucker rats, insensitive to leptin, did not. CCK
      signaling in VAN of obese Zucker rats was reduced, preventing CCK-induced up
      regulation of Y2 receptor and down-regulation of melanin concentrating hormone 1
      receptor (MCH1R) and cannabinoid receptor (CB1). In VAN from diet-induced obese
      (DIO) Sprague Dawley rats, previously shown to become leptin resistant, we
      demonstrated that the reduction in EGR1 expression resulted in decreased
      sensitivity of VAN to CCK and reduced CCK-induced inhibition of food intake. The
      lowered sensitivity of VAN to CCK in DIO rats resulted in a decrease in Y2
      expression and increased CB1 and MCH1R expression. These effects coincided with
      the onset of hyperphagia in DIO rats. CONCLUSIONS: Leptin signaling in VAN is
      required for appropriate CCK signaling and satiation. In response to high fat
      feeding, the onset of leptin resistance reduces the sensitivity of VAN to CCK
      thus reducing the satiating effects of CCK.

PMID- 22412962
TI  - Spoligotyping and drug resistance analysis of Mycobacterium tuberculosis strains
      from national survey in China.
AB  - BACKGROUND: Tuberculosis (TB), caused by Mycobacterium tuberculosis complex
      (MTBC), is one of the major causes of death in the world today. Although China
      has the second largest global case rate of tuberculosis, a systematic study of TB
      prevalence in China has not been completed. From 2006 to 2007, the base line
      surveillance of tuberculosis was carried out by Ministry of Health, and more than
      4000 representative strains were selected from 31 provinces in China.
      METHODOLOGY/PRINCIPAL FINDINGS: The aim of the present research was to survey the
      genotypes of representative Mycobacterium tuberculosis (M. tuberculosis) strains
      from China using spacer oligonucleotide typing (spoligotyping), and to analyze
      the relationship between genotype and drug resistance for the first time. A total
      of 4017 clinical isolates were collected from 2007 to 2008 throughout China.
      Among those M. tuberculosis isolates, 2500 (62.2%) isolates were Beijing
      genotypes. The percentage of Beijing genotypes in northern China was higher than
      in southern China (76.5% vs. 53.2%). Additionally, the frequencies of rifampin
      resistant, ofloxacin-resistant and multidrug-resistant isolates were
      significantly higher in Beijing genotype strains than non-Beijing strains.
      Furthermore, a novel genotype named "China Southern genotype (CS)" was only
      isolated from Fujian and Guangdong provinces. Hence, it is very practical to
      uncover the reason for prevalence of the CS type in southern China.
      CONCLUSIONS/SIGNIFICANCE: In conclusion, Beijing family genotypes were still the
      predominant genotype throughout China, which exhibited a greater correlation with
      rifampin-resistance, ofloxacin-resistance and MDR phenotypes than other TB
      spoligotypes, and some regions of China showed several unique characters in the
      distribution of M. tuberculosis genotypes. Our research represents an important
      contribution for the TB control and research community, which completes broad
      pictures on drug resistance levels and distribution of M. tuberculosis strain
      types over China.

PMID- 22412961
TI  - Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and
      social behaviors.
AB  - The delta family of ionotropic glutamate receptors consists of glutamate delta1
      (GluD1) and glutamate delta2 (GluD2) receptors. While the role of GluD2 in the
      regulation of cerebellar physiology is well understood, the function of GluD1 in
      the central nervous system remains elusive. We demonstrate for the first time
      that deletion of GluD1 leads to abnormal emotional and social behaviors. We found
      that GluD1 knockout mice (GluD1 KO) were hyperactive, manifested lower anxiety
      like behavior, depression-like behavior in a forced swim test and robust
      aggression in the resident-intruder test. Chronic lithium rescued the depression
      like behavior in GluD1 KO. GluD1 KO mice also manifested deficits in social
      interaction. In the sociability test, GluD1 KO mice spent more time interacting
      with an inanimate object compared to a conspecific mouse. D-Cycloserine (DCS)
      administration was able to rescue social interaction deficits observed in GluD1
      KO mice. At a molecular level synaptoneurosome preparations revealed lower GluA1
      and GluA2 subunit expression in the prefrontal cortex and higher GluA1, GluK2 and
      PSD95 expression in the amygdala of GluD1 KO. Moreover, DCS normalized the lower
      GluA1 expression in prefrontal cortex of GluD1 KO. We propose that deletion of
      GluD1 leads to aberrant circuitry in prefrontal cortex and amygdala owing to its
      potential role in presynaptic differentiation and synapse formation. Furthermore,
      these findings are in agreement with the human genetic studies suggesting a
      strong association of GRID1 gene with several neuropsychiatric disorders
      including schizophrenia, bipolar disorder, autism spectrum disorders and major
      depressive disorder.

PMID- 22412963
TI  - Renal failure affects the enzymatic activities of the three first steps in
      hepatic heme biosynthesis in the acute intermittent porphyria mouse.
AB  - Chronic kidney disease is a long-term complication in acute intermittent
      porphyria (AIP). The pathophysiological significance of hepatic overproduction of
      the porphyrin precursors aminolevulinate acid (ALA) and porphobilinogen (PBG) in
      chronic kidney disease is unclear. We have investigated the effect of repetitive
      acute attacks on renal function and the effect of total or five-sixth nephrectomy
      causing renal insufficiency on hepatic heme synthesis in the porphobilinogen
      deaminase (PBGD)-deficient (AIP) mouse. Phenobarbital challenge in the AIP-mice
      increased urinary porphyrin precursor excretion. Successive attacks throughout 14
      weeks led to minor renal lesions with no impact on renal function. In the liver
      of wild type and AIP mice, 5/6 nephrectomy enhanced transcription of the first
      and rate-limiting ALA synthase. As a consequence, urinary PBG excretion increased
      in AIP mice. The PBG/ALA ratio increased from 1 in sham operated AIP animals to
      over 5 (males) and over 13 (females) in the 5/6 nephrectomized mice. Total
      nephrectomy caused a rapid decrease in PBGD activity without changes in enzyme
      protein level in the AIP mice but not in the wild type animals. In conclusion,
      high concentration of porphyrin precursors had little impact on renal function.
      However, progressive renal insufficiency aggravates porphyria attacks and
      increases the PBG/ALA ratio, which should be considered a warning sign for
      potentially life-threatening impairment in AIP patients with signs of renal
      failure.

PMID- 22412964
TI  - Theta-burst stimulation-induced plasticity over primary somatosensory cortex
      changes somatosensory temporal discrimination in healthy humans.
AB  - BACKGROUND: The somatosensory temporal discrimination threshold (STDT) measures
      the ability to perceive two stimuli as being sequential. Precisely how the single
      cerebral structures contribute in controlling the STDT is partially known and no
      information is available about whether STDT can be modulated by plasticity
      inducing protocols. METHODOLOGY/PRINCIPAL FINDINGS: To investigate how the
      cortical and cerebellar areas contribute to the STDT we used transcranial
      magnetic stimulation and a neuronavigation system. We enrolled 18 healthy
      volunteers and 10 of these completed all the experimental sessions, including the
      control experiments. STDT was measured on the left hand before and after applying
      continuous theta-burst stimulation (cTBS) on the right primary somatosensory area
      (S1), pre-supplementary motor area (pre-SMA), right dorsolateral prefrontal
      cortex (DLPFC) and left cerebellar hemisphere. We then investigated whether
      intermittent theta-burst stimulation (iTBS) on the right S1 improved the STDT.
      After right S1 cTBS, STDT values increased whereas after iTBS to the same
      cortical site they decreased. cTBS over the DLPFC and left lateral cerebellum
      left the STDT statistically unchanged. cTBS over the pre-SMA also left the STDT
      statistically unchanged, but it increased the number of errors subjects made in
      distinguishing trials testing a single stimulus and those testing paired stimuli.
      CONCLUSIONS/SIGNIFICANCE: Our findings obtained by applying TBS to the cortical
      areas involved in processing sensory discrimination show that the STDT is encoded
      in S1, possibly depends on intrinsic S1 neural circuit properties, and can be
      modulated by plasticity-inducing TBS protocols delivered over S1. Our findings,
      giving further insight into mechanisms involved in somatosensory temporal
      discrimination, help interpret STDT abnormalities in movement disorders including
      dystonia and Parkinson's disease.

PMID- 22412965
TI  - Reef sharks exhibit site-fidelity and higher relative abundance in marine
      reserves on the Mesoamerican Barrier Reef.
AB  - Carcharhinid sharks can make up a large fraction of the top predators inhabiting
      tropical marine ecosystems and have declined in many regions due to intense
      fishing pressure. There is some support for the hypothesis that carcharhinid
      species that complete their life-cycle within coral reef ecosystems, hereafter
      referred to as "reef sharks", are more abundant inside no-take marine reserves
      due to a reduction in fishing pressure (i.e., they benefit from marine reserves).
      Key predictions of this hypothesis are that (a) individual reef sharks exhibit
      high site-fidelity to these protected areas and (b) their relative abundance will
      generally be higher in these areas compared to fished reefs. To test this
      hypothesis for the first time in Caribbean coral reef ecosystems we combined
      acoustic monitoring and baited remote underwater video (BRUV) surveys to measure
      reef shark site-fidelity and relative abundance, respectively. We focused on the
      Caribbean reef shark (Carcharhinus perezi), the most common reef shark in the
      Western Atlantic, at Glover's Reef Marine Reserve (GRMR), Belize. Acoustically
      tagged sharks (N = 34) were detected throughout the year at this location and
      exhibited strong site-fidelity. Shark presence or absence on 200 BRUVs deployed
      at GRMR and three other sites (another reserve site and two fished reefs) showed
      that the factor "marine reserve" had a significant positive effect on reef shark
      presence. We rejected environmental factors or site-environment interactions as
      predominant drivers of this pattern. These results are consistent with the
      hypothesis that marine reserves can benefit reef shark populations and we suggest
      new hypotheses to determine the underlying mechanism(s) involved: reduced fishing
      mortality or enhanced prey availability.

PMID- 22412966
TI  - You are what you eat: within-subject increases in fruit and vegetable consumption
      confer beneficial skin-color changes.
AB  - BACKGROUND: Fruit and vegetable consumption and ingestion of carotenoids have
      been found to be associated with human skin-color (yellowness) in a recent cross
      sectional study. This carotenoid-based coloration contributes beneficially to the
      appearance of health in humans and is held to be a sexually selected cue of
      condition in other species. METHODOLOGY AND PRINCIPAL FINDINGS: Here we
      investigate the effects of fruit and vegetable consumption on skin-color
      longitudinally to determine the magnitude and duration of diet change required to
      change skin-color perceptibly. Diet and skin-color were recorded at baseline and
      after three and six weeks, in a group of 35 individuals who were without makeup,
      self-tanning agents and/or recent intensive UV exposure. Six-week changes in
      fruit and vegetable consumption were significantly correlated with changes in
      skin redness and yellowness over this period, and diet-linked skin reflectance
      changes were significantly associated with the spectral absorption of carotenoids
      and not melanin. We also used psychophysical methods to investigate the minimum
      color change required to confer perceptibly healthier and more attractive skin
      coloration. Modest dietary changes are required to enhance apparent health (2.91
      portions per day) and attractiveness (3.30 portions). CONCLUSIONS: Increased
      fruit and vegetable consumption confers measurable and perceptibly beneficial
      effects on Caucasian skin appearance within six weeks. This effect could
      potentially be used as a motivational tool in dietary intervention.

PMID- 22412967
TI  - Mab21l2 is essential for embryonic heart and liver development.
AB  - During mouse embryogenesis, proper formation of the heart and liver is especially
      important and is crucial for embryonic viability. In this study, we showed that
      Mab21l2 was expressed in the trabecular and compact myocardium, and that deletion
      of Mab21l2 resulted in a reduction of the trabecular myocardium and thinning of
      the compact myocardium. Mab21l2-deficient embryonic hearts had decreased
      expression of genes that regulate cell proliferation and apoptosis of
      cardiomyocytes. These results show that Mab21l2 functions during heart
      development by regulating the expression of such genes. Mab21l2 was also
      expressed in the septum transversum mesenchyme (STM). Epicardial progenitor cells
      are localized to the anterior surface of the STM (proepicardium), and
      proepicardial cells migrate onto the surface of the heart and form the
      epicardium, which plays an important role in heart development. The rest of the
      STM is essential for the growth and survival of hepatoblasts, which are
      bipotential progenitors for hepatocytes and cholangiocytes. Proepicardial cells
      in Mab21l2-deficient embryos had defects in cell proliferation, which led to a
      small proepicardium, in which alpha4 integrin expression, which is essential for
      the migration of proepicardial cells, was down-regulated, suggesting that defects
      occurred in its migration. In Mab21l2-deficient embryos, epicardial formation was
      defective, suggesting that Mab21l2 plays important roles in epicardial formation
      through the regulation of the cell proliferation of proepicardial cells and the
      migratory process of proepicardial cells. Mab21l2-deficient embryos also
      exhibited hypoplasia of the STM surrounding hepatoblasts and decreased
      hepatoblast proliferation with a resultant loss of defective morphogenesis of the
      liver. These findings demonstrate that Mab21l2 plays a crucial role in both heart
      and liver development through STM formation.

PMID- 22412968
TI  - Differential expression of metabolic genes in tumor and stromal components of
      primary and metastatic loci in pancreatic adenocarcinoma.
AB  - BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer related
      deaths in the United States with a five-year survival rate of 6%. It is
      characterized by extremely aggressive tumor growth rate and high incidence of
      metastasis. One of the most common and profound biochemical phenotypes of animal
      and human cancer cells is their ability to metabolize glucose at high rates, even
      under aerobic conditions. However, the contribution of metabolic
      interrelationships between tumor cells and cells of the surrounding
      microenvironment to the progression of cancer is not well understood. We
      evaluated differential expression of metabolic genes and, hence, metabolic
      pathways in primary tumor and metastases of patients with pancreatic
      adenocarcinoma. METHODS AND FINDINGS: We analyzed the metabolic gene (those
      involved in glycolysis, tri-carboxylic acid pathway, pentose-phosphate pathway
      and fatty acid metabolism) expression profiles of primary and metastatic lesions
      from pancreatic cancer patients by gene expression arrays. We observed two
      principal results: genes that were upregulated in primary and most of the
      metastatic lesions; and genes that were upregulated only in specific metastatic
      lesions in a site-specific manner. Immunohistochemical (IHC) analyses of several
      metabolic gene products confirmed the gene expression patterns at the protein
      level. The IHC analyses also revealed differential tumor and stromal expression
      patterns of metabolic enzymes that were correlated with the metastasis sites.
      CONCLUSIONS: Here, we present the first comprehensive studies that establish
      differential metabolic status of tumor and stromal components and elevation of
      aerobic glycolysis gene expression in pancreatic cancer.

PMID- 22412969
TI  - Micro-RNA profiling in human serum reveals compartment-specific roles of miR-571
      and miR-652 in liver cirrhosis.
AB  - BACKGROUND AND AIMS: Micro-RNAs (miRNAs) have recently emerged as crucial
      modulators of molecular processes involved in chronic liver diseases. The few
      miRNAs with previously proposed roles in liver cirrhosis were identified in
      screening approaches on liver parenchyma, mostly in rodent models. Therefore, in
      the present study we performed a systematic screening approach in order to
      identify miRNAs with altered levels in the serum of patients with chronic liver
      disease and liver cirrhosis. METHODS: We performed a systematic, array-based
      miRNA expression analysis on serum samples from patients with liver cirrhosis. In
      functional experiments we evaluated the relationship between alterations of miRNA
      serum levels and their role in distinct cellular compartments involved in hepatic
      cirrhosis. RESULTS: The array analysis and the subsequent confirmation by qPCR in
      a larger patient cohort identified significant alterations in serum levels of miR
      513-3p, miR-571 and miR-652, three previously uncharacterized miRNAs, in patients
      with alcoholic or hepatitis C induced liver cirrhosis. Of these, miR-571 serum
      levels closely correlated with disease stages, thus revealing potential as a
      novel biomarker for hepatic cirrhosis. Further analysis revealed that up
      regulation of miR-571 in serum reflected a concordant regulation in cirrhotic
      liver tissue. In isolated primary human liver cells, miR-571 was up-regulated in
      human hepatocytes and hepatic stellate cells in response to the pro-fibrogenic
      cytokine TGF-beta. In contrast, alterations in serum levels of miR-652 were stage
      independent, reflecting a concordant down-regulation of this miRNA in circulating
      monocytes of patients with liver cirrhosis, which was inducible by
      proinflammatory stimuli like bacterial lipopolysaccharide. CONCLUSION:
      Alterations of miR571 and miR-652 serum levels in patients with chronic liver
      disease reflect their putative roles in the mediation of fibrogenic and
      inflammatory processes in distinct cellular compartments involved in the
      pathogenesis of liver cirrhosis.

PMID- 22412970
TI  - Detection of IL28B SNP DNA from buccal epithelial cells, small amounts of serum,
      and dried blood spots.
AB  - BACKGROUND & AIMS: Point mutations in the coding region of the interleukin 28
      gene (rs12979860) have recently been identified for predicting the outcome of
      treatment of hepatitis C virus infection. This polymorphism detection was based
      on whole blood DNA extraction. Alternatively, DNA for genetic diagnosis has been
      derived from buccal epithelial cells (BEC), dried blood spots (DBS), and genomic
      DNA from serum. The aim of the study was to investigate the reliability and
      accuracy of alternative routes of testing for single nucleotide polymorphism
      allele rs12979860CC. METHODS: Blood, plasma, and sera samples from 200 patients
      were extracted (400 uL). Buccal smears were tested using an FTA card. To simulate
      postal delay, we tested the influence of storage at ambient temperature on the
      different sources of DNA at five time points (baseline, 48 h, 6 days, 9 days, and
      12 days). RESULTS: There was 100% concordance between blood, plasma, sera, and
      BEC, validating the use of DNA extracted from BEC collected on cytology brushes
      for genetic testing. Genetic variations in HPTR1 gene were detected using smear
      technique in blood smear (3620 copies) as well as in buccal smears (5870 copies).
      These results are similar to those for whole blood diluted at 1/10. A minimum of
      0.04 uL, 4 uL, and 40 uL was necessary to obtain exploitable results respectively
      for whole blood, sera, and plasma. No significant variation between each time
      point was observed for the different sources of DNA. IL28B SNPs analysis at these
      different time points showed the same results using the four sources of DNA.
      CONCLUSION: We demonstrated that genomic DNA extraction from buccal cells, small
      amounts of serum, and dried blood spots is an alternative to DNA extracted from
      peripheral blood cells and is helpful in retrospective and prospective studies
      for multiple genetic markers, specifically in hard-to-reach individuals.

PMID- 22412971
TI  - EPHA2 polymorphisms and age-related cataract in India.
AB  - OBJECTIVE: We investigated whether previously reported single nucleotide
      polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in
      India. METHODS: We carried out a population-based genetic association study. We
      enumerated randomly sampled villages in two areas of north and south India to
      identify people aged 40 and over. Participants attended a clinical examination
      including lens photography and provided a blood sample for genotyping. Lens
      images were graded by the Lens Opacification Classification System (LOCS III).
      Cataract was defined as a LOCS III grade of nuclear >=4, cortical >=3, posterior
      sub-capsular (PSC) >=2, or dense opacities or aphakia/pseudophakia in either eye.
      We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted
      from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time
      PCR. We used logistic regression with robust standard errors to examine the
      association between cataract and the EPHA2 SNPs, adjusting for age, sex and
      location. RESULTS: 7418 participants had data on at least one of the SNPs
      investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium
      (p>0.05). There was no association of rs3754334 with cataract or type of
      cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared
      to the major homozygote genotype were associated with cortical cataract, Odds
      ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2,
      7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02
      and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of
      SNPs with nuclear cataract or a combined variable of any type of cataract
      including operated cataract. CONCLUSIONS: Our results in the Indian population
      agree with previous studies of the association of EPHA2 variants with cortical
      cataracts. We report new findings for the association with PSC which is
      particularly prevalent in Indians.

PMID- 22412972
TI  - Lung adenocarcinoma of never smokers and smokers harbor differential regions of
      genetic alteration and exhibit different levels of genomic instability.
AB  - Recent evidence suggests that the observed clinical distinctions between lung
      tumors in smokers and never smokers (NS) extend beyond specific gene mutations,
      such as EGFR, EML4-ALK, and KRAS, some of which have been translated into
      targeted therapies. However, the molecular alterations identified thus far cannot
      explain all of the clinical and biological disparities observed in lung tumors of
      NS and smokers. To this end, we performed an unbiased genome-wide, comparative
      study to identify novel genomic aberrations that differ between smokers and NS.
      High resolution whole genome DNA copy number profiling of 69 lung adenocarcinomas
      from smokers (n = 39) and NS (n = 30) revealed both global and regional
      disparities in the tumor genomes of these two groups. We found that NS lung
      tumors had a greater proportion of their genomes altered than those of smokers.
      Moreover, copy number gains on chromosomes 5q, 7p, and 16p occurred more
      frequently in NS. We validated our findings in two independently generated public
      datasets. Our findings provide a novel line of evidence distinguishing genetic
      differences between smoker and NS lung tumors, namely, that the extent of
      segmental genomic alterations is greater in NS tumors. Collectively, our findings
      provide evidence that these lung tumors are globally and genetically different,
      which implies they are likely driven by distinct molecular mechanisms.

PMID- 22412973
TI  - Evidence that Ca2+ within the microdomain of the L-type voltage gated Ca2+
      channel activates ERK in MIN6 cells in response to glucagon-like peptide-1.
AB  - Glucagon like peptide-1 (GLP-1) is released from intestinal L-cells in response
      to nutrient ingestion and acts upon pancreatic beta-cells potentiating glucose
      stimulated insulin secretion and stimulating beta-cell proliferation,
      differentiation, survival and gene transcription. These effects are mediated
      through the activation of multiple signal transduction pathways including the
      extracellular regulated kinase (ERK) pathway. We have previously reported that
      GLP-1 activates ERK through a mechanism dependent upon the influx of
      extracellular Ca(2+) through L-type voltage gated Ca(2+) channels (VGCC).
      However, the mechanism by which L-type VGCCs couple to the ERK signalling pathway
      in pancreatic beta-cells is poorly understood. In this report, we characterise
      the relationship between L-type VGCC mediated changes in intracellular Ca(2+)
      concentration ([Ca(2+)](i)) and the activation of ERK, and demonstrate that the
      sustained activation of ERK (up to 30 min) in response to GLP-1 requires the
      continual activation of the L-type VGCC yet does not require a sustained increase
      in global [Ca(2+)](i) or Ca(2+) efflux from the endoplasmic reticulum. Moreover,
      sustained elevation of [Ca(2+)](i) induced by ionomycin is insufficient to
      stimulate the prolonged activation of ERK. Using the cell permeant Ca(2+)
      chelators, EGTA-AM and BAPTA-AM, to determine the spatial dynamics of L-type VGCC
      dependent Ca(2+) signalling to ERK, we provide evidence that a sustained increase
      in Ca(2+) within the microdomain of the L-type VGCC is sufficient for signalling
      to ERK and that this plays an important role in GLP-1- stimulated ERK activation.

PMID- 22412974
TI  - Cigarette smoke upregulates rat coronary artery endothelin receptors in vivo.
AB  - BACKGROUND: Cigarette smoking is a strong cardiovascular risk factor and
      endothelin (ET) receptors are related to coronary artery diseases. The present
      study established an in vivo secondhand smoke (SHS) exposure model and
      investigated the hypothesis that cigarette smoke induces ET receptor upregulation
      in rat coronary arteries and its possible underlying mechanisms.
      METHODOLOGY/PRINCIPAL FINDINGS: Rats were exposed to SHS for 200 min daily for 8
      weeks. The coronary arteries were isolated and examined. The vasoconstriction was
      studied by a sensitive myograph. The expression of mRNA and protein for receptors
      was examined by real-time PCR, Western blot and immunofluorescence. Compared to
      fresh air exposure, SHS increased contractile responses mediated by endothelin
      type A (ET(A)) and type B (ET(B)) receptors in coronary arteries. In parallel,
      the expression of mRNA and protein for ET(A) and ET(B) receptors of smoke exposed
      rats were higher than that of animals exposed to fresh air, suggesting that SHS
      upregulates ET(A) and ET(B) receptors in coronary arteries in vivo.
      Immunofluorescence staining showed that the enhanced receptor expression was
      localized to the smooth muscle cells of coronary arteries. The protein levels of
      phosphorylated (p)-Raf-1 and p-ERK1/2 in smoke exposed rats were significantly
      higher than in control rats, demonstrating that SHS induces the activation of the
      Raf/ERK/MAPK pathway. Treatment with Raf-1 inhibitor GW5074 suppressed SHS
      induced enhanced contraction mediated by ET(A) receptors, and inhibited the
      elevated mRNA and protein levels of ET(A) and ET(B) receptors caused by SHS. The
      results of correlation and regression analysis showed that phosphorylation of Raf
      and ERK1/2 were independent determinants to affect protein expression of ET(B)
      and ET(A) receptors. CONCLUSIONS/SIGNIFICANCE: Cigarette smoke upregulates ET(B)
      and ET(A) receptors in rat coronary artery, which is associated with the
      activation of the Raf/ERK/MAPK pathway.

PMID- 22412976
TI  - Comparison of blue light-filtering IOLs and UV light-filtering IOLs for cataract
      surgery: a meta-analysis.
AB  - BACKGROUND: A number of published randomized controlled trials have been
      conducted to evaluate visual performance of blue light-filtering intraocular
      lenses (IOL) and UV light-filtering intraocular lenses (IOL) after cataract
      phacoemulsification surgery. However, results have not always been consistent.
      Therefore, we carried out a meta-analysis to compare the effectiveness of blue
      light-filtering IOLs versus UV light-filtering IOLs in cataract surgery. METHODS
      AND FINDINGS: Comprehensive searches of PubMed, Embase, Cochrane Library and the
      Chinese BioMedical literature databases were performed using web-based search
      engines. Fifteen trials (1690 eyes) were included for systematic review, and 11
      of 15 studies were included in this meta-analysis. The results showed that there
      were no significant differences in postoperative mean best corrected visual
      acuity, contrast sensitivity, overall color vision, or in the blue light spectrum
      under photopic light conditions between blue light-filtering IOLs and UV light
      filtering IOLs [WMD = -0.01, 95%CI (-0.03, 0.01), P = 0.46; WMD = 0.07, 95%CI (
      0.04, 0.19), P = 0.20; SMD = 0.14, 95%CI (-0.33, 0.60), P = 0.566; SMD = 0.20,
      95%CI (-0.04, 0.43), P = 0.099]. However, color vision with blue light-filtering
      IOLs was significantly reduced in the blue light spectrum under mesopic light
      conditions [SMD = 0.74, 95%CI (0.29, 1.18), P = 0.001]. CONCLUSION: This meta
      analysis demonstrates that postoperative visual performance with blue light
      filtering IOLs is approximately equal to that of UV light-filtering IOLs after
      cataract surgery, but color vision with blue light-filtering IOLs demonstrated
      some compromise in the blue light spectrum under mesopic light conditions.

PMID- 22412975
TI  - Targeting bone remodeling by isoflavone and 3,3'-diindolylmethane in the context
      of prostate cancer bone metastasis.
AB  - Prostate cancer (PCa) bone metastases have long been believed to be osteoblastic
      because of bone remodeling leading to the formation of new bone. However, recent
      studies have shown increased osteolytic activity in the beginning stages of PCa
      bone metastases, suggesting that targeting both osteolytic and osteoblastic
      mediators would likely inhibit bone remodeling and PCa bone metastasis. In this
      study, we found that PCa cells could stimulate differentiation of osteoclasts and
      osteoblasts through the up-regulation of RANKL, RUNX2 and osteopontin, promoting
      bone remodeling. Interestingly, we found that formulated isoflavone and 3,3'
      diindolylmethane (BR-DIM) were able to inhibit the differentiation of osteoclasts
      and osteoblasts through the inhibition of cell signal transduction in RANKL,
      osteoblastic, and PCa cell signaling. Moreover, we found that isoflavone and BR
      DIM down-regulated the expression of miR-92a, which is known to be associated
      with RANKL signaling, EMT and cancer progression. By pathway and network
      analysis, we also observed the regulatory effects of isoflavone and BR-DIM on
      multiple signaling pathways such as AR/PSA, NKX3-1/Akt/p27, MITF, etc. Therefore,
      isoflavone and BR-DIM with their multi-targeted effects could be useful for the
      prevention of PCa progression, especially by attenuating bone metastasis
      mechanisms.

PMID- 22412977
TI  - Detailed mitochondrial phenotyping by high resolution metabolomics.
AB  - Mitochondrial phenotype is complex and difficult to define at the level of
      individual cell types. Newer metabolic profiling methods provide information on
      dozens of metabolic pathways from a relatively small sample. This pilot study
      used "top-down" metabolic profiling to determine the spectrum of metabolites
      present in liver mitochondria. High resolution mass spectral analyses and
      multivariate statistical tests provided global metabolic information about
      mitochondria and showed that liver mitochondria possess a significant phenotype
      based on gender and genotype. The data also show that mitochondria contain a
      large number of unidentified chemicals.

PMID- 22412978
TI  - Characterization of the chromosome 4 genes that affect fluconazole-induced disomy
      formation in Cryptococcus neoformans.
AB  - Heteroresistance in Cryptococcus neoformans is an intrinsic adaptive resistance
      to azoles and the heteroresistant phenotype is associated with disomic
      chromosomes. Two chromosome 1 (Chr1) genes, ERG11, the fluconazole target, and
      AFR1, a drug transporter, were reported as major factors in the emergence of Chr1
      disomy. In the present study, we show Chr4 to be the second most frequently
      formed disomy at high concentrations of fluconazole (FLC) and characterize the
      importance of resident genes contributing to disomy formation. We deleted nine
      Chr4 genes presumed to have functions in ergosterol biosynthesis, membrane
      composition/integrity or drug transportation that could influence Chr4 disomy
      under FLC stress. Of these nine, disruption of three genes homologous to Sey1 (a
      GTPase), Glo3 and Gcs2 (the ADP-ribosylation factor GTPase activating proteins)
      significantly reduced the frequency of Chr4 disomy in heteroresistant clones.
      Furthermore, FLC resistant clones derived from sey1Deltaglo3Delta did not show
      disomy of either Chr4 or Chr1 but instead had increased the copy number of the
      genes proximal to ERG11 locus on Chr1. Since the three genes are critical for the
      integrity of endoplasmic reticulum (ER) in Saccharomyces cerevisiae, we used
      Sec61beta-GFP fusion as a marker to study the ER in the mutants. The cytoplasmic
      ER was found to be elongated in sey1Delta but without any discernable alteration
      in gcs2Delta and glo3Delta under fluorescence microscopy. The aberrant ER
      morphology of all three mutant strains, however, was discernable by transmission
      electron microscopy. A 3D reconstruction using Focused Ion Beam Scanning Electron
      Microscopy (FIB-SEM) revealed considerably reduced reticulation in the ER of
      glo3Delta and gcs2Delta strains. In sey1Delta, ER reticulation was barely
      detectable and cisternae were expanded extensively compared to the wild type
      strains. These data suggest that the genes required for maintenance of ER
      integrity are important for the formation of disomic chromosomes in C. neoformans
      under azole stress.

PMID- 22412979
TI  - US public support for vaccine donation to poorer countries in the 2009 H1N1
      pandemic.
AB  - BACKGROUND: During the 2009 H1N1 pandemic, the global health community sought to
      make vaccine available "in developing nations in the same timeframe as developed
      nations." However, richer nations placed advance orders with manufacturers,
      leaving poorer nations dependent on the quantity and timing of vaccine donations
      by manufacturers and rich nations. Knowledge of public support for timely
      donations could be important to policy makers during the next pandemic. We
      explored what the United States (US) public believes about vaccine donation by
      its country to poorer countries. METHODS AND FINDINGS: We surveyed 2079 US adults
      between January 22(nd) and February 1(st) 2010 about their beliefs regarding
      vaccine donation to poorer countries. Income (p = 0.014), objective priority
      status (p = 0.005), nativity, party affiliation, and political ideology (p<0.001)
      were significantly related to views on the amount of vaccine to be donated.
      Though party affiliation and political ideology were related to willingness to
      donate vaccine (p<0.001), there was bipartisan support for timely donations of
      10% of the US vaccine supply so that those "at risk in poorer countries can get
      the vaccine at the same time" as those at risk in the US. CONCLUSIONS: We suggest
      that the US and other developed nations would do well to bolster support with
      education and public discussion on this issue prior to an emerging pandemic when
      emotional reactions could potentially influence support for donation. We conclude
      that given our evidence for bipartisan support for timely donations, it may be
      necessary to design multiple arguments, from utilitarian to moral, to strengthen
      public and policy makers' support for donations.

PMID- 22412980
TI  - CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing
      immune cell accumulation and production of pathogenic IgG-antibodies.
AB  - BACKGROUND: Adipose tissue inflammation fuels the metabolic syndrome. We recently
      reported that CD40L--an established marker and mediator of cardiovascular disease
      -induces inflammatory cytokine production in adipose cells in vitro. Here, we
      tested the hypothesis that CD40L deficiency modulates adipose tissue inflammation
      in vivo. METHODOLOGY/PRINCIPAL FINDINGS: WT or CD40L(-/-) mice consumed a high
      fat diet (HFD) for 20 weeks. Inflammatory cell recruitment was impaired in mice
      lacking CD40L as shown by a decrease of adipose tissue macrophages, B-cells, and
      an increase in protective T-regulatory cells. Mechanistically, CD40L-deficient
      mice expressed significantly lower levels of the pro-inflammatory chemokine MCP-1
      both, locally in adipose tissue and systemically in plasma. Moreover, levels of
      pro-inflammatory IgG-antibodies against oxidized lipids were reduced in CD40L(-/
      ) mice. Also, circulating low-density lipoproteins and insulin levels were lower
      in CD40L(-/-) mice. However, CD40L(-/-) mice consuming HFD were not protected
      from the onset of diet-induced obesity (DIO), insulin resistance, and hepatic
      steatosis, suggesting that CD40L selectively limits the inflammatory features of
      diet-induced obesity rather than its metabolic phenotype. Interestingly, CD40L(-/
      ) mice consuming a low fat diet (LFD) showed both, a favorable inflammatory and
      metabolic phenotype characterized by diminished weight gain, improved insulin
      tolerance, and attenuated plasma adipokine levels. CONCLUSION: We present the
      novel finding that CD40L deficiency limits adipose tissue inflammation in vivo.
      These findings identify CD40L as a potential mediator at the interface of
      cardiovascular and metabolic disease.

PMID- 22412981
TI  - Long-lasting consequences of neonatal maternal separation on social behaviors in
      ovariectomized female mice.
AB  - Maternal separation (MS) stress is known to induce long-lasting alterations in
      emotional and anxiety-related behaviors, but effects on social behaviors are not
      well defined. The present study examined MS effects on female social behaviors in
      the social investigation (SIT) and social preference (SPT) tests, in addition to
      non-social behaviors in the open-field (OFT) and light-dark transition (LDT)
      tests in C57BL/6J mice. All females were tested as ovariectomized to eliminate
      confounding effects of endogenous estrogen during behavioral testing. Daily MS (3
      hr) from postnatal day 1 to 14 did not affect anxiety levels in LDT, but were
      elevated in OFT with modified behavioral responses to the novel environment.
      Furthermore, MS altered social investigative behaviors and preference patterns
      toward unfamiliar stimulus mice in SIT and short- and long-term SPT paradigms. In
      SIT, MS reduced social investigation duration and increased number of stretched
      approaches towards both female and male unfamiliar stimulus mice, suggesting
      increased social anxiety levels in MS females. Similarly, MS heightened levels of
      social anxiety during short-term SPT but no MS effect on social preference was
      found. On the other hand, MS females displayed a distinctive preference for
      female stimuli, unlike control females, when tested for long-term SPT over a
      prolonged period of 5 days. Evaluation of FosB expression in the paraventricular
      nucleus, medial and central amygdala following stimulus exposure demonstrated
      greater number of FosB immunopositive cells in all three brain regions in MS
      females compared to control females. These results suggest that MS females might
      differ in neuroendocrine responses toward unfamiliar female and male opponents,
      which may be associated with modifications in social behaviors found in the
      present study. Taken together, this study provides new evidence that early life
      stress modifies female social behaviors by highlighting alterations in behavioral
      responses to situations involving social as well as non-social novelty.

PMID- 22412982
TI  - Prospective and retrospective time estimates of children: a comparison based on
      ecological tasks.
AB  - Children's time estimation literature lacks of studies comparing prospective and
      retrospective time estimates of long lasting ecological tasks, i.e. tasks
      reflecting children's daily activities. In the present study, children were asked
      to estimate prospectively or retrospectively how much time they played a video
      game or read a magazine. Regardless of the task, the results revealed that
      prospective time estimates were longer than the retrospective ones. Also, time
      estimates of the video game task were longer, less accurate and more variable
      than those of the reading task. The results are discussed in the light of the
      current literature about time estimation of long lasting ecological tasks.

PMID- 22412983
TI  - Expression patterns of genes involved in sugar metabolism and accumulation during
      apple fruit development.
AB  - Both sorbitol and sucrose are imported into apple fruit from leaves. The
      metabolism of sorbitol and sucrose fuels fruit growth and development, and
      accumulation of sugars in fruit is central to the edible quality of apple.
      However, our understanding of the mechanisms controlling sugar metabolism and
      accumulation in apple remains quite limited. We identified members of various
      gene families encoding key enzymes or transporters involved in sugar metabolism
      and accumulation in apple fruit using homology searches and comparison of their
      expression patterns in different tissues, and analyzed the relationship of their
      transcripts with enzyme activities and sugar accumulation during fruit
      development. At the early stage of fruit development, the transcript levels of
      sorbitol dehydrogenase, cell wall invertase, neutral invertase, sucrose synthase,
      fructokinase and hexokinase are high, and the resulting high enzyme activities
      are responsible for the rapid utilization of the imported sorbitol and sucrose
      for fruit growth, with low levels of sugar accumulation. As the fruit continues
      to grow due to cell expansion, the transcript levels and activities of these
      enzymes are down-regulated, with concomitant accumulation of fructose and
      elevated transcript levels of tonoplast monosaccharide transporters (TMTs),
      MdTMT1 and MdTMT2; the excess carbon is converted into starch. At the late stage
      of fruit development, sucrose accumulation is enhanced, consistent with the
      elevated expression of sucrose-phosphate synthase (SPS), MdSPS5 and MdSPS6, and
      an increase in its total activity. Our data indicate that sugar metabolism and
      accumulation in apple fruit is developmentally regulated. This represents a
      comprehensive analysis of the genes involved in sugar metabolism and accumulation
      in apple, which will serve as a platform for further studies on the functions of
      these genes and subsequent manipulation of sugar metabolism and fruit quality
      traits related to carbohydrates.

PMID- 22412984
TI  - Differential expression of cytokines in response to respiratory syncytial virus
      infection of calves with high or low circulating 25-hydroxyvitamin D3.
AB  - Deficiency of serum levels of 25-hydroxyvitamin D(3) has been related to
      increased risk of lower respiratory tract infections in children. Respiratory
      syncytial virus (RSV) is a leading cause of low respiratory tract infections in
      infants and young children. The neonatal calf model of RSV infection shares many
      features in common with RSV infection in infants and children. In the present
      study, we hypothesized that calves with low circulating levels of 25
      hydroxyvitamin D(3) (25(OH)D(3)) would be more susceptible to RSV infection than
      calves with high circulating levels of 25(OH)D(3). Calves were fed milk replacer
      diets with different levels of vitamin D for a 10 wk period to establish two
      treatment groups, one with high (177 ng/ml) and one with low (32.5 ng/ml)
      circulating 25(OH)D(3). Animals were experimentally infected via aerosol
      challenge with RSV. Data on circulating 25(OH)D(3) levels showed that high and
      low concentrations of 25(OH)D(3) were maintained during infection. At necropsy,
      lung lesions due to RSV were similar in the two vitamin D treatment groups. We
      show for the first time that RSV infection activates the vitamin D intracrine
      pathway in the inflamed lung. Importantly, however, we observed that cytokines
      frequently inhibited by this pathway in vitro are, in fact, either significantly
      upregulated (IL-12p40) or unaffected (IFN-gamma) in the lungs of RSV-infected
      calves with high circulating levels of 25(OH)D(3). Our data indicate that while
      vitamin D does have an immunomodulatory role during RSV infection, there was no
      significant impact on pathogenesis during the early phases of RSV infection.
      Further examination of the potential effects of vitamin D status on RSV disease
      resolution will require longer-term studies with immunologically sufficient and
      deficient vitamin D levels.

PMID- 22412985
TI  - Characterization of Salmonella type III secretion hyper-activity which results in
      biofilm-like cell aggregation.
AB  - We have previously reported the cloning of the Salmonella enterica serovar
      Typhimurium SPI-1 secretion system and the use of this clone to functionally
      complement a DeltaSPI-1 strain for type III secretion activity. In the current
      study, we discovered that S. Typhimurium cultures containing cloned SPI-1 display
      an adherent biofilm and cell clumps in the media. This phenotype was associated
      with hyper-expression of SPI-1 type III secretion functions. The biofilm and cell
      clumps were associated with copious amounts of secreted SPI-1 protein substrates
      SipA, SipB, SipC, SopB, SopE, and SptP. We used a C-terminally FLAG-tagged SipA
      protein to further demonstrate SPI-1 substrate association with the cell
      aggregates using fluorescence microscopy and immunogold electron microscopy.
      Different S. Typhimurium backgrounds and both flagellated and nonflagellated
      strains displayed the biofilm phenotype. Mutations in genes essential for known
      bacterial biofilm pathways (bcsA, csgBA, bapA) did not affect the biofilms formed
      here indicating that this phenomenon is independent of established biofilm
      mechanisms. The SPI-1-mediated biofilm was able to massively recruit heterologous
      non-biofilm forming bacteria into the adherent cell community. The results
      indicate a bacterial aggregation phenotype mediated by elevated SPI-1 type III
      secretion activity with applications for engineered biofilm formation, protein
      purification strategies, and antigen display.

PMID- 22412986
TI  - Activation of interferon regulatory factor 5 by site specific phosphorylation.
AB  - The cellular defense to infection depends on accurate activation of transcription
      factors and expression of select innate immunity genes. Interferon regulatory
      factor 5 (IRF5), a risk factor for systemic lupus erythematosus, is activated in
      response to pathogen recognition receptor engagement and downstream effector
      molecules. We find the nucleotide-binding oligomerization domain containing
      protein 2 (NOD2) receptor to be a significant activator of IRF5. Phosphorylation
      is key to the regulation of IRF5, but the precise phosphorylation sites in IRF5
      remained to be identified. We used mass spectrometry to identify for the first
      time specific residues that are phosphorylated in response to TANK-binding kinase
      1 (TBK-1), tumor necrosis factor receptor-associated factor 6 (TRAF6), or
      receptor interacting protein 2 (RIP2). RIP2, a kinase known to function
      downstream of NOD2, was the most effective activator of IRF5-regulated gene
      expression. To determine if the phosphorylated residues are required or
      sufficient for IRF5 activity, aspartic acid phosphomimetic substitutions or
      inactivating alanine substitutions were tested. Phosphorylation of carboxyl
      serines 451 and 462 appear the primary trigger of IRF5 function in nuclear
      accumulation, transcription, and apoptosis. Results indicate polyubiquitination
      of IRF5 does not play a major role in its transcriptional activity, and that
      ubiquitination and phosphorylation are independent modifications.

PMID- 22412987
TI  - Cell proliferation and migration are modulated by Cdk-1-phosphorylated
      endothelial-monocyte activating polypeptide II.
AB  - BACKGROUND: Endothelial-Monocyte Activating Polypeptide (EMAP II) is a secreted
      protein with well-established anti-angiogenic activities. Intracellular EMAP II
      expression is increased during fetal development at epithelial/mesenchymal
      boundaries and in pathophysiologic fibroproliferative cells of bronchopulmonary
      dysplasia, emphysema, and scar fibroblast tissue following myocardial ischemia.
      Precise function and regulation of intracellular EMAP II, however, has not been
      explored to date. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that high
      intracellular EMAP II suppresses cellular proliferation by slowing progression
      through the G2M cell cycle transition in epithelium and fibroblast. Furthermore,
      EMAP II binds to and is phosphorylated by Cdk1, and exhibits nuclear/cytoplasmic
      partitioning, with only nuclear EMAP II being phosphorylated. We observed that
      extracellular secreted EMAP II induces endothelial cell apoptosis, where as
      excess intracellular EMAP II facilitates epithelial and fibroblast cells
      migration. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that EMAP II has
      specific intracellular effects, and that this intracellular function appears to
      antagonize its extracellular anti-angiogenic effects during fetal development and
      pulmonary disease progression.

PMID- 22412988
TI  - Evidence that descending cortical axons are essential for thalamocortical axons
      to cross the pallial-subpallial boundary in the embryonic forebrain.
AB  - Developing thalamocortical axons traverse the subpallium to reach the cortex
      located in the pallium. We tested the hypothesis that descending corticofugal
      axons are important for guiding thalamocortical axons across the pallial
      subpallial boundary, using conditional mutagenesis to assess the effects of
      blocking corticofugal axonal development without disrupting thalamus, subpallium
      or the pallial-subpallial boundary. We found that thalamic axons still traversed
      the subpallium in topographic order but did not cross the pallial-subpallial
      boundary. Co-culture experiments indicated that the inability of thalamic axons
      to cross the boundary was not explained by mutant cortex developing a long-range
      chemorepulsive action on thalamic axons. On the contrary, cortex from conditional
      mutants retained its thalamic axonal growth-promoting activity and continued to
      express Nrg-1, which is responsible for this stimulatory effect. When mutant
      cortex was replaced with control cortex, corticofugal efferents were restored and
      thalamic axons from conditional mutants associated with them and crossed the
      pallial-subpallial boundary. Our study provides the most compelling evidence to
      date that cortical efferents are required to guide thalamocortical axons across
      the pallial-subpallial boundary, which is otherwise hostile to thalamic axons.
      These results support the hypothesis that thalamic axons grow from subpallium to
      cortex guided by cortical efferents, with stimulation from diffusible cortical
      growth-promoting factors.

PMID- 22412989
TI  - Desert ants learn vibration and magnetic landmarks.
AB  - The desert ants Cataglyphis navigate not only by path integration but also by
      using visual and olfactory landmarks to pinpoint the nest entrance. Here we show
      that Cataglyphis noda can additionally use magnetic and vibrational landmarks as
      nest-defining cues. The magnetic field may typically provide directional rather
      than positional information, and vibrational signals so far have been shown to be
      involved in social behavior. Thus it remains questionable if magnetic and
      vibration landmarks are usually provided by the ants' habitat as nest-defining
      cues. However, our results point to the flexibility of the ants' navigational
      system, which even makes use of cues that are probably most often sensed in a
      different context.

PMID- 22412990
TI  - Interactions between amyloid-beta and hemoglobin: implications for amyloid plaque
      formation in Alzheimer's disease.
AB  - Accumulation of amyloid-beta (Abeta) peptides in the brain is one of the central
      pathogenic events in Alzheimer's disease (AD). However, why and how Abeta
      aggregates within the brain of AD patients remains elusive. Previously, we
      demonstrated hemoglobin (Hb) binds to Abeta and co-localizes with the plaque and
      vascular amyloid deposits in post-mortem AD brains. In this study, we further
      characterize the interactions between Hb and Abeta in vitro and in vivo and
      report the following observations: 1) the binding of Hb to Abeta required iron
      containing heme; 2) other heme-containing proteins, such as myoglobin and
      cytochrome C, also bound to Abeta; 3) hemin-induced cytotoxicity was reduced in
      neuroblastoma cells by low levels of Abeta; 4) Hb was detected in neurons and
      glial cells of post-mortem AD brains and was up-regulated in aging and APP/PS1
      transgenic mice; 5) microinjection of human Hb into the dorsal hippocampi of the
      APP/PS1 transgenic mice induced the formation of an envelope-like structure
      composed of Abeta surrounding the Hb droplets. Our results reveal an enhanced
      endogenous expression of Hb in aging brain cells, probably serving as a
      compensatory mechanism against hypoxia. In addition, Abeta binds to Hb and other
      hemoproteins via the iron-containing heme moiety, thereby reducing Hb/heme/iron
      induced cytotoxicity. As some of the brain Hb could be derived from the
      peripheral circulation due to a compromised blood-brain barrier frequently
      observed in aged and AD brains, our work also suggests the genesis of some
      plaques may be a consequence of sustained amyloid accretion at sites of vascular
      injury.

PMID- 22412991
TI  - Hospital cluster of HBV infection: molecular evidence of patient-to-patient
      transmission through lancing device.
AB  - INTRODUCTION: In western countries the transmission of hepatitis B virus (HBV)
      transmission through multi-patients lancing devices has been inferred since early
      '90s, however no study has ever provided biological evidence which directly link
      these device with HBV cross-infection. Here we present results of an outbreak
      investigation which could associate, by molecular techniques, the use of lancing
      device on multiple patients with HBV transmission in an Italian oncohematology
      unit. METHODS: The outbreak investigation was designed as a retrospective cohort
      study to identify all potential cases. All cases identified were eventually
      confirmed through molecular epidemiology techniques. Audit of personnel including
      extensive review of infection control measures and reviewing personnel's tests
      for HBV was done identify transmission route. RESULTS: Between 4 May 2006 and 21
      February 2007, six incident cases of HBV infection were reported among 162
      patients admitted in the oncohematology. The subsequent molecular instigation
      proved that 3 out 6 incident cases and one prevalent cases (already infected with
      HBV at the admission) represented a monophyletic cluster of infection. The
      eventual environmental investigation found that an identical HBV viral strain was
      present on a multi-patients lancing device in use in the unit and the inferential
      analysis showed a statistically significant association between undergoing
      lancing procedures and the infection. DISCUSSION: This investigation provide
      molecular evidence to link a HBV infection cluster to multi-patients lancing
      device and highlights that patients undergoing capillary blood sampling by non
      disposable lancing device may face an unacceptable increased risk of HBV
      infection. Therefore we believe that multi-patients lancing devices should be
      banned from healthcare settings and replace with disposable safety lancets that
      permanently retract to prevent the use of the same device on multiple patients.
      The use of non-disposable lancing devices should be restricted to individual use
      at patients' home.

PMID- 22412992
TI  - Impact of enhanced Staphylococcus DNA extraction on microbial community measures
      in cystic fibrosis sputum.
AB  - Staphylococcus aureus is a common constituent of the bacterial community
      inhabiting the airways of persons with cystic fibrosis (CF). Culture-independent
      studies have shown that this species is often present in relatively high
      abundance and would therefore be expected to exert a pronounced effect on
      measures of CF airway bacterial community structure. We investigated the impact
      of DNA extraction method on pyrosequencing-based measures of Staphylococcus
      abundance and bacterial community structure in 17 sputum samples from five CF
      patients. Staphylococcus was detected in fewer samples when DNA was extracted
      using a standard bacterial lysis method compared to when DNA was extracted using
      a lysis buffer amended with lysostaphin and lysozyme. The standard lysis method
      resulted in significantly lower measures of Staphylococcus relative abundance and
      higher levels of community diversity, richness, and evenness compared to the
      lysostaphin-lysozyme modified method. Measures of community dynamics in serial
      sputum samples from the same individual were nevertheless highly concordant
      between the two DNA extraction methods. These results illustrate the impact of
      DNA preparation method on measures of Staphylococcus abundance and bacterial
      community structures in studies of the airways microbiota in CF.

PMID- 22412993
TI  - Foxp2 mutations impair auditory-motor association learning.
AB  - Heterozygous mutations of the human FOXP2 transcription factor gene cause the
      best-described examples of monogenic speech and language disorders. Acquisition
      of proficient spoken language involves auditory-guided vocal learning, a
      specialized form of sensory-motor association learning. The impact of etiological
      Foxp2 mutations on learning of auditory-motor associations in mammals has not
      been determined yet. Here, we directly assess this type of learning using a newly
      developed conditioned avoidance paradigm in a shuttle-box for mice. We show
      striking deficits in mice heterozygous for either of two different Foxp2
      mutations previously implicated in human speech disorders. Both mutations cause
      delays in acquiring new motor skills. The magnitude of impairments in association
      learning, however, depends on the nature of the mutation. Mice with a missense
      mutation in the DNA-binding domain are able to learn, but at a much slower rate
      than wild type animals, while mice carrying an early nonsense mutation learn very
      little. These results are consistent with expression of Foxp2 in distributed
      circuits of the cortex, striatum and cerebellum that are known to play key roles
      in acquisition of motor skills and sensory-motor association learning, and
      suggest differing in vivo effects for distinct variants of the Foxp2 protein.
      Given the importance of such networks for the acquisition of human spoken
      language, and the fact that similar mutations in human FOXP2 cause problems with
      speech development, this work opens up a new perspective on the use of mouse
      models for understanding pathways underlying speech and language disorders.

PMID- 22412994
TI  - Epistasis for growth rate and total metabolic flux in yeast.
AB  - Studies of interactions between gene deletions repeatedly show that the effect of
      epistasis on the growth of yeast cells is roughly null or barely positive. These
      observations relate generally to the pace of growth, its costs in terms of
      required metabolites and energy are unknown. We measured the maximum rate at
      which yeast cultures grow and amounts of glucose they consume per synthesized
      biomass for strains with none, single, or double gene deletions. Because all
      strains were maintained under a fermentative mode of growth and thus shared a
      common pattern of metabolic processes, we used the rate of glucose uptake as a
      proxy for the total flux of metabolites and energy. In the tested sample, the
      double deletions showed null or slightly positive epistasis both for the mean
      growth and mean flux. This concordance is explained by the fact that average
      efficiency of converting glucose into biomass was nearly constant, that is, it
      did not change with the strength of growth effect. Individual changes in the
      efficiency caused by gene deletions did have a genetic basis as they were
      consistent over several environments and transmitted between single and double
      deletion strains indicating that the efficiency of growth, although independent
      of its rate, was appreciably heritable. Together, our results suggest that data
      on the rate of growth can be used as a proxy for the rate of total metabolism
      when the goal is to find strong individual interactions or estimate the mean
      epistatic effect. However, it may be necessary to assay both growth and flux in
      order to detect smaller individual effects of epistasis.

PMID- 22412996
TI  - Persistent humoral immune responses in the CNS limit recovery of reactivated
      murine cytomegalovirus.
AB  - BACKGROUND: Experimental infection of the mouse brain with murine CMV (MCMV)
      elicits neuroimmune responses that terminate acute infection while simultaneously
      preventing extensive bystander damage. Previous studies have determined that
      CD8(+) T lymphocytes are required to restrict acute, productive MCMV infection
      within the central nervous system (CNS). In this study, we investigated the
      contribution of humoral immune responses in control of MCMV brain infection.
      METHODOLOGY/PRINCIPAL FINDINGS: Utilizing our MCMV brain infection model, we
      investigated B-lymphocyte-lineage cells and assessed their role in controlling
      the recovery of reactivated virus from latently infected brain tissue. Brain
      infiltrating leukocytes were first phenotyped using markers indicative of B
      lymphocytes and plasma cells. Results obtained during these studies showed a
      steady increase in the recruitment of B-lymphocyte-lineage cells into the brain
      throughout the time-course of viral infection. Further, MCMV-specific antibody
      secreting cells (ASC) were detected within the infiltrating leukocyte population
      using an ELISPOT assay. Immunohistochemical studies of brain sections revealed co
      localization of CD138(+) cells with either IgG or IgM. Additional
      immunohistochemical staining for MCMV early antigen 1 (E1, m112-113), a reported
      marker of viral latency in neurons, confirmed its expression in the brain during
      latent infection. Finally, using B-cell deficient (Jh(-/-)) mice we demonstrated
      that B-lymphocytes control recovery of reactivated virus from latently-infected
      brain tissue. A significantly higher rate of reactivated virus was recovered from
      the brains of Jh(-/-) mice when compared to Wt animals. CONCLUSION: Taken
      together, these results demonstrate that MCMV infection triggers accumulation and
      persistence of B-lymphocyte-lineage cells within the brain, which produce
      antibodies and play a significant role in controlling reactivated virus.

PMID- 22412997
TI  - Grasping kinematics from the perspective of the individual digits: a modelling
      study.
AB  - Grasping is a prototype of human motor coordination. Nevertheless, it is not
      known what determines the typical movement patterns of grasping. One way to
      approach this issue is by building models. We developed a model based on the
      movements of the individual digits. In our model the following objectives were
      taken into account for each digit: move smoothly to the preselected goal position
      on the object without hitting other surfaces, arrive at about the same time as
      the other digit and never move too far from the other digit. These objectives
      were implemented by regarding the tips of the digits as point masses with a
      spring between them, each attracted to its goal position and repelled from
      objects' surfaces. Their movements were damped. Using a single set of parameters,
      our model can reproduce a wider variety of experimental findings than any
      previous model of grasping. Apart from reproducing known effects (even the angles
      under which digits approach trapezoidal objects' surfaces, which no other model
      can explain), our model predicted that the increase in maximum grip aperture with
      object size should be greater for blocks than for cylinders. A survey of the
      literature shows that this is indeed how humans behave. The model can also
      adequately predict how single digit pointing movements are made. This supports
      the idea that grasping kinematics follow from the movements of the individual
      digits.

PMID- 22412995
TI  - Sociodemographic factors and clinical conditions associated to hospitalization in
      influenza A (H1N1) 2009 virus infected patients in Spain, 2009-2010.
AB  - The emergence and pandemic spread of a new strain of influenza A (H1N1) virus in
      2009 resulted in a serious alarm in clinical and public health services all over
      the world. One distinguishing feature of this new influenza pandemic was the
      different profile of hospitalized patients compared to those from traditional
      seasonal influenza infections. Our goal was to analyze sociodemographic and
      clinical factors associated to hospitalization following infection by influenza
      A(H1N1) virus. We report the results of a Spanish nationwide study with
      laboratory confirmed infection by the new pandemic virus in a case-control design
      based on hospitalized patients. The main risk factors for hospitalization of
      influenza A (H1N1) 2009 were determined to be obesity (BMI>=40, with an odds
      ratio [OR] 14.27), hematological neoplasia (OR 10.71), chronic heart disease,
      COPD (OR 5.16) and neurological disease, among the clinical conditions, whereas
      low education level and some ethnic backgrounds (Gypsies and Amerinds) were the
      sociodemographic variables found associated to hospitalization. The presence of
      any clinical condition of moderate risk almost triples the risk of
      hospitalization (OR 2.88) and high risk conditions raise this value markedly (OR
      6.43). The risk of hospitalization increased proportionally when for two (OR
      2.08) or for three or more (OR 4.86) risk factors were simultaneously present in
      the same patient. These findings should be considered when a new influenza virus
      appears in the human population.

PMID- 22412999
TI  - Glutathione peroxidase-1 primes pro-inflammatory cytokine production after LPS
      challenge in vivo.
AB  - Reactive oxygen species produced during the innate immune response to LPS are
      important agents of anti-pathogen defence but may also cause oxidative lung
      damage. Glutathione peroxidase-1 (gpx-1) is an anti-oxidant enzyme that may
      protect lungs from such damage. We assessed the in vivo importance of gpx-1 in
      LPS-induced lung inflammation. Male wild-type (WT) or gpx-1 deficient (gpx-1(-/
      )) mice were treated intranasally with PBS or 10 ug LPS and killed 3 and 24 h
      post LPS. Lungs were lavaged with PBS and then harvested for inflammatory marker
      expression. LPS caused an intense neutrophilia in WT BALF evident 3 and 24 h post
      challenge that was reduced in gpx-1(-/-) mice. In addition, LPS-treated gpx-1(-/
      ) mice had significantly fewer macrophages than LPS-treated WT mice. To
      understand the basis for this paradoxical reduction we assessed inflammatory
      cytokines and proteases at protein and transcript levels. MMP-9 expression and
      net gelatinase activity in BALF of gpx-1(-/-) mice treated with LPS for 3 and 24
      h was no different to that found in LPS-treated WT mice. BALF from LPS-treated
      gpx-1(-/-) mice (3 h) had less TNF-alpha, MIP-2 and GM-CSF protein than LPS
      treated WT mice. In contrast, LPS-induced increases in TNF-alpha, MIP-2 and GM
      CSF mRNA expression in WT mice were similar to those observed in gpx-1(-/-) mice.
      These attenuated protein levels were unexpectedly not mirrored by reduced mRNA
      transcripts but were associated with increased 20S proteasome expression. Thus,
      these data suggest that gpx-1 primes pro-inflammatory cytokine production after
      LPS challenge in vivo.

PMID- 22413000
TI  - Glutamine acts as a neuroprotectant against DNA damage, beta-amyloid and H2O2
      induced stress.
AB  - Glutamine is the most abundant free amino acid in the human blood stream and is
      'conditionally essential' to cells. Its intracellular levels are regulated both
      by the uptake of extracellular glutamine via specific transport systems and by
      its intracellular synthesis by glutamine synthetase (GS). Adding to the
      regulatory complexity, when extracellular glutamine is reduced GS protein levels
      rise. Unfortunately, this excess GS can be maladaptive. GS overexpression is
      neurotoxic especially if the cells are in a low-glutamine medium. Similarly, in
      low glutamine, the levels of multiple stress response proteins are reduced
      rendering cells hypersensitive to H(2)O(2), zinc salts and DNA damage. These
      altered responses may have particular relevance to neurodegenerative diseases of
      aging. GS activity and glutamine levels are lower in the Alzheimer's disease (AD)
      brain, and a fraction of AD hippocampal neurons have dramatically increased GS
      levels compared with control subjects. We validated the importance of these
      observations by showing that raising glutamine levels in the medium protects
      cultured neuronal cells against the amyloid peptide, Abeta. Further, a 10-day
      course of dietary glutamine supplementation reduced inflammation-induced neuronal
      cell cycle activation, tau phosphorylation and ATM-activation in two different
      mouse models of familial AD while raising the levels of two synaptic proteins,
      VAMP2 and synaptophysin. Together, our observations suggest that healthy neuronal
      cells require both intracellular and extracellular glutamine, and that the
      neuroprotective effects of glutamine supplementation may prove beneficial in the
      treatment of AD.

PMID- 22412998
TI  - Fatal cases of influenza A(H3N2) in children: insights from whole genome sequence
      analysis.
AB  - During the Northern Hemisphere winter of 2003-2004 the emergence of a novel
      influenza antigenic variant, A/Fujian/411/2002-like(H3N2), was associated with an
      unusually high number of fatalities in children. Seventeen fatal cases in the UK
      were laboratory confirmed for Fujian/411-like viruses. To look for phylogenetic
      patterns and genetic markers that might be associated with increased virulence,
      sequencing and phylogenetic analysis of the whole genomes of 63 viruses isolated
      from fatal cases and non fatal "control" cases was undertaken. The analysis
      revealed the circulation of two main genetic groups, I and II, both of which
      contained viruses from fatal cases. No associated amino acid substitutions could
      be linked with an exclusive or higher occurrence in fatal cases. The Fujian/411
      like viruses in genetic groups I and II completely displaced other A(H3N2)
      viruses, but they disappeared after 2004. This study shows that two A(H3N2) virus
      genotypes circulated exclusively during the winter of 2003-2004 in the UK and
      caused an unusually high number of deaths in children. Host factors related to
      immune state and differences in genetic background between patients may also play
      important roles in determining the outcome of an influenza infection.

PMID- 22413001
TI  - Identification and characterization of the RLIP/RALBP1 interacting protein Xreps1
      in Xenopus laevis early development.
AB  - BACKGROUND: The FGF/Ras/Ral/RLIP pathway is required for the gastrulation process
      during the early development of vertebrates. The Ral Interacting Protein (RLIP
      also known as RalBP1) interacts with GTP-bound Ral proteins. RLIP/RalBP1 is a
      modular protein capable of participating in many cellular functions.
      METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of RLIP in early
      development, a two-hybrid screening using a library of maternal cDNAs of the
      amphibian Xenopus laevis was performed. Xreps1 was isolated as a partner of
      RLIP/RalBP1 and its function was studied. The mutual interacting domains of
      Xreps1 and Xenopus RLIP (XRLIP) were identified. Xreps1 expressed in vivo, or
      synthesized in vitro, interacts with in vitro expressed XRLIP. Interestingly,
      targeting of Xreps1 or the Xreps1-binding domain of XRLIP (XRLIP(469-636)) to the
      plasma membrane through their fusion to the CAAX sequence induces a
      hyperpigmentation phenotype of the embryo. This hyperpigmented phenotype induced
      by XRLIP(469-636)-CAAX can be rescued by co-expression of a deletion mutant of
      Xreps1 restricted to the RLIP-binding domain (Xreps1(RLIP-BD)) but not by co
      expression of a cDNA coding for a longer form of Xreps1. CONCLUSION/SIGNIFICANCE:
      We demonstrate here that RLIP/RalBP1, an effector of Ral involved in receptor
      mediated endocytosis and in the regulation of actin dynamics during embryonic
      development, also interacts with Reps1. Although these two proteins are present
      early during embryonic development, they are active only at the end of
      gastrulation. Our results suggest that the interaction between RLIP and Reps1 is
      negatively controlled during the cleavage stage of development, which is
      characterized by rapid mitosis. Later in development, Reps1 is required for the
      normal function of the ectodermic cell, and its targeting into the plasma
      membrane affects the stability of the ectoderm.

PMID- 22413002
TI  - Coordinated expression of tristetraprolin post-transcriptionally attenuates
      mitogenic induction of the oncogenic Ser/Thr kinase Pim-1.
AB  - The serine/threonine kinase Pim-1 directs selected signaling events that promote
      cell growth and survival and is overexpressed in diverse human cancers. Pim-1
      expression is tightly controlled through multiple mechanisms, including
      regulation of mRNA turnover. In several cultured cell models, mitogenic
      stimulation rapidly induced and stabilized PIM1 mRNA, however, vigorous
      destabilization 4-6 hours later helped restore basal expression levels.
      Acceleration of PIM1 mRNA turnover coincided with accumulation of tristetraprolin
      (TTP), an mRNA-destabilizing protein that targets transcripts containing AU-rich
      elements. TTP binds PIM1 mRNA in cells, and suppresses its expression by
      accelerating mRNA decay. Reporter mRNA decay assays localized the TTP-regulated
      mRNA decay element to a discrete AU-rich sequence in the distal 3'-untranslated
      region that binds TTP. These data suggest that coordinated stimulation of TTP and
      PIM1 expression limits the magnitude and duration of PIM1 mRNA accumulation by
      accelerating its degradation as TTP protein levels increase. Consistent with this
      model, PIM1 and TTP mRNA levels were well correlated across selected human tissue
      panels, and PIM1 mRNA was induced to significantly higher levels in mitogen
      stimulated fibroblasts from TTP-deficient mice. Together, these data support a
      model whereby induction of TTP mediates a negative feedback circuit to limit
      expression of selected mitogen-activated genes.

PMID- 22413004
TI  - Percutaneous cryoablation for the treatment of medically inoperable stage I non
      small cell lung cancer.
AB  - BACKGROUND: To evaluate the midterm results of percutaneous cryoablation for
      medically inoperable stage I non-small cell lung cancer. METHODOLOGY/PRINCIPAL
      FINDINGS: Between January 2004 and June 2010, 160 patients underwent computer
      tomography guided percutaneous cryoablation for lung tumors at our institution.
      Of these patients, histologically proven stage I lung cancer patients with more
      than one year of follow-up, were retrospectively reviewed. All of these patients
      were considered to be medically inoperable with Charlson comorbidity index of 3
      or greater. Follow-up was based primarily on computed tomography. There were 22
      patients with 34 tumors who underwent 25 sessions of cryoablation treatment.
      Complications were pneumothoraces in 7 treatments (28%, chest tube required in
      one treatment), and pleural effusions in 8 treatments (31%). The observation
      period ranged from 12-68 months, average 29+/-19 months, median 23 months. Local
      tumor progression was observed in one tumor (3%). Mean local tumor progression
      free interval was 69+/-2 months. One patient died of lung cancer progression at
      68 months. Two patients died of acute exacerbations of idiopathic pulmonary
      fibrosis which were not considered to be directly associated with cryoablation,
      at 12 and 18 months, respectively. The overall 2- and 3-year survivals were 88%
      and 88%, respectively. Mean overall survival was 62+/-4 months. Median overall
      survival was 68 months. The disease-free 2- and 3-year survivals were 78% and
      67%, respectively. Mean disease-free survival was 46+/-6 months. Pulmonary
      function tests were done in 16 patients (18 treatments) before and after
      cryoablation. Percentage of predicted vital capacity, and percentage of predicted
      forced expiratory volume in 1 second, did not differ significantly before and
      after cryoablation (93+/-23 versus 90+/-21, and 70+/-11 versus 70+/-12,
      respectively). CONCLUSIONS/SIGNIFICANCE: Although further accumulation of data is
      necessary regarding efficacy, cryoablation may be a feasible option in medically
      inoperable stage I lung cancer patients.

PMID- 22413003
TI  - Meta-profiles of gene expression during aging: limited similarities between mouse
      and human and an unexpectedly decreased inflammatory signature.
AB  - BACKGROUND: Skin aging is associated with intrinsic processes that compromise the
      structure of the extracellular matrix while promoting loss of functional and
      regenerative capacity. These processes are accompanied by a large-scale shift in
      gene expression, but underlying mechanisms are not understood and conservation of
      these mechanisms between humans and mice is uncertain. RESULTS: We used genome
      wide expression profiling to investigate the aging skin transcriptome. In humans,
      age-related shifts in gene expression were sex-specific. In females, aging
      increased expression of transcripts associated with T-cells, B-cells and
      dendritic cells, and decreased expression of genes in regions with elevated Zeb1,
      AP-2 and YY1 motif density. In males, however, these effects were contrasting or
      absent. When age-associated gene expression patterns in human skin were compared
      to those in tail skin from CB6F1 mice, overall human-mouse correspondence was
      weak. Moreover, inflammatory gene expression patterns were not induced with aging
      of mouse tail skin, and well-known aging biomarkers were in fact decreased (e.g.,
      Clec7a, Lyz1 and Lyz2). These unexpected patterns and weak human-mouse
      correspondence may be due to decreased abundance of antigen presenting cells in
      mouse tail skin with age. CONCLUSIONS: Aging is generally associated with a pro
      inflammatory state, but we have identified an exception to this pattern with
      aging of CB6F1 mouse tail skin. Aging therefore does not uniformly heighten
      inflammatory status across all mouse tissues. Furthermore, we identified both
      intercellular and intracellular mechanisms of transcriptome aging, including
      those that are sex- and species-specific.

PMID- 22413005
TI  - T4-related bacteriophage LIMEstone isolates for the control of soft rot on potato
      caused by 'Dickeya solani'.
AB  - The bacterium 'Dickeya solani', an aggressive biovar 3 variant of Dickeya
      dianthicola, causes rotting and blackleg in potato. To control this pathogen
      using bacteriophage therapy, we isolated and characterized two closely related
      and specific bacteriophages, vB_DsoM_LIMEstone1 and vB_DsoM_LIMEstone2. The
      LIMEstone phages have a T4-related genome organization and share DNA similarity
      with Salmonella phage ViI. Microbiological and molecular characterization of the
      phages deemed them suitable and promising for use in phage therapy. The phages
      reduced disease incidence and severity on potato tubers in laboratory assays. In
      addition, in a field trial of potato tubers, when infected with 'Dickeya solani',
      the experimental phage treatment resulted in a higher yield. These results form
      the basis for the development of a bacteriophage-based biocontrol of potato
      plants and tubers as an alternative for the use of antibiotics.

PMID- 22413006
TI  - Children base their investment on calculated pay-off.
AB  - To investigate the rise of economic abilities during development we studied
      children aged between 3 and 10 in an exchange situation requiring them to
      calculate their investment based on different offers. One experimenter gave back
      a reward twice the amount given by the children, and a second always gave back
      the same quantity regardless of the amount received. To maximize pay-offs
      children had to invest a maximal amount with the first, and a minimal amount with
      the second. About one third of the 5-year-olds and most 7- and 10-year-olds were
      able to adjust their investment according to the partner, while all 3-year-olds
      failed. Such performances should be related to the rise of cognitive and social
      skills after 4 years.

PMID- 22413007
TI  - Differences in spontaneously avoiding or approaching mice reflect differences in
      CB1-mediated signaling of dorsal striatal transmission.
AB  - Approach or avoidance behaviors are accompanied by perceptual vigilance for,
      affective reactivity to and behavioral predisposition towards rewarding or
      punitive stimuli, respectively. We detected three subpopulations of C57BL/6J mice
      that responded with avoiding, balancing or approaching behaviors not induced by
      any experimental manipulation but spontaneously displayed in an
      approach/avoidance conflict task. Although the detailed neuronal mechanisms
      underlying the balancing between approach and avoidance are not fully clarified,
      there is growing evidence that endocannabinoid system (ECS) plays a critical role
      in the control of these balancing actions. The sensitivity of dorsal striatal
      synapses to the activation of cannabinoid CB1 receptors was investigated in the
      subpopulations of spontaneously avoiding, balancing or approaching mice. Avoiding
      animals displayed decreased control of CB1 receptors on GABAergic striatal
      transmission and in parallel increase of behavioral inhibition. Conversely,
      approaching animals exhibited increased control of CB1 receptors and in parallel
      increase of explorative behavior. Balancing animals reacted with balanced
      responses between approach and avoidance patterns. Treating avoiding animals with
      URB597 (fatty acid amide hydrolase inhibitor) or approaching animals with AM251
      (CB1 receptor inverse agonist) reverted their respective behavioral and
      electrophysiological patterns. Therefore, enhanced or reduced CB1-mediated
      control on dorsal striatal transmission represents the synaptic hallmark of the
      approach or avoidance behavior, respectively. Thus, the opposite spontaneous
      responses to conflicting stimuli are modulated by a different involvement of
      endocannabinoid signaling of dorsal striatal neurons in the range of
      temperamental traits related to individual differences.

PMID- 22413008
TI  - IL-9 induces VEGF secretion from human mast cells and IL-9/IL-9 receptor genes
      are overexpressed in atopic dermatitis.
AB  - Interleukin 9 (IL-9) has been implicated in mast cell-related inflammatory
      diseases, such as asthma, where vascular endothelial growth factor (VEGF) is
      involved. Here we report that IL-9 (10-20 ng/ml) induces gene expression and
      secretion of VEGF from human LAD2. IL-9 does not induce mast cell degranulation
      or the release of other mediators (IL-1, IL-8, or TNF). VEGF production in
      response to IL-9 involves STAT-3 activation. The effect is inhibited (about 80%)
      by the STAT-3 inhibitor, Stattic. Gene-expression of IL-9 and IL-9 receptor is
      significantly increased in lesional skin areas of atopic dermatitis (AD) patients
      as compared to normal control skin, while serum IL-9 is not different from
      controls. These results imply that functional interactions between IL-9 and mast
      cells leading to VEGF release contribute to the initiation/propagation of the
      pathogenesis of AD, a skin inflammatory disease.

PMID- 22413009
TI  - Glucocorticosteroids differentially regulate MMP-9 and neutrophil elastase in
      COPD.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is currently the fifth
      leading cause of death worldwide. Neutrophilic inflammation is prominent,
      worsened during infective exacerbations and is refractory to glucocorticosteroids
      (GCs). Deregulated neutrophilic inflammation can cause excessive matrix
      degradation through proteinase release. Gelatinase and azurophilic granules
      within neutrophils are a major source of matrix metalloproteinase (MMP)-9 and
      neutrophil elastase (NE), respectively, which are elevated in COPD. METHODS:
      Secreted MMP-9 and NE activity in BALF were stratified according to GOLD severity
      stages. The regulation of secreted NE and MMP-9 in isolated blood neutrophils was
      investigated using a pharmacological approach. In vivo release of MMP-9 and NE in
      mice exposed to cigarette smoke (CS) and/or the TLR agonist lipopolysaccharide
      (LPS) in the presence of dexamethasone (Dex) was investigated. RESULTS:
      Neutrophil activation as assessed by NE release was increased in severe COPD (36
      fold, GOLD II vs. IV). MMP-9 levels (8-fold) and activity (21-fold) were also
      elevated in severe COPD, and this activity was strongly associated with BALF
      neutrophils (r = 0.92, p<0.001), but not macrophages (r = 0.48, p = 0.13). In
      vitro, release of NE and MMP-9 from fMLP stimulated blood neutrophils was
      insensitive to Dex and attenuated by the PI3K inhibitor, wortmannin. In vivo, GC
      resistant neutrophil activation (NE release) was only seen in mice exposed to CS
      and LPS. In addition, GC refractory MMP-9 expression was only associated with
      neutrophil activation. CONCLUSIONS: As neutrophils become activated with
      increasing COPD severity, they become an important source of NE and MMP-9
      activity, which secrete proteinases independently of TIMPs. Furthermore, as NE
      and MMP-9 release was resistant to GC, targeting of the PI3K pathway may offer an
      alternative pathway to combating this proteinase imbalance in severe COPD.

PMID- 22413010
TI  - Stearoyl-CoA desaturase-1 (SCD1) augments saturated fatty acid-induced lipid
      accumulation and inhibits apoptosis in cardiac myocytes.
AB  - Mismatch between the uptake and utilization of long-chain fatty acids in the
      myocardium leads to abnormally high intracellular fatty acid concentration, which
      ultimately induces myocardial dysfunction. Stearoyl-Coenzyme A desaturase-1
      (SCD1) is a rate-limiting enzyme that converts saturated fatty acids (SFAs) to
      monounsaturated fatty acids. Previous studies have shown that SCD1-deficinent
      mice are protected from insulin resistance and diet-induced obesity; however, the
      role of SCD1 in the heart remains to be determined. We examined the expression of
      SCD1 in obese rat hearts induced by a sucrose-rich diet for 3 months. We also
      examined the effect of SCD1 on myocardial energy metabolism and apoptotic cell
      death in neonatal rat cardiac myocytes in the presence of SFAs. Here we showed
      that the expression of SCD1 increases 3.6-fold without measurable change in the
      expression of lipogenic genes in the heart of rats fed a high-sucrose diet.
      Forced SCD1 expression augmented palmitic acid-induced lipid accumulation, but
      attenuated excess fatty acid oxidation and restored reduced glucose oxidation. Of
      importance, SCD1 substantially inhibited SFA-induced caspase 3 activation,
      ceramide synthesis, diacylglycerol synthesis, apoptotic cell death, and
      mitochondrial reactive oxygen species (ROS) generation. Experiments using SCD1
      siRNA confirmed these observations. Furthermore, we showed that exposure of
      cardiac myocytes to glucose and insulin induced SCD1 expression. Our results
      indicate that SCD1 is highly regulated by a metabolic syndrome component in the
      heart, and such induction of SCD1 serves to alleviate SFA-induced adverse fatty
      acid catabolism, and eventually to prevent SFAs-induced apoptosis.

PMID- 22413011
TI  - Cadherin-23 mediates heterotypic cell-cell adhesion between breast cancer
      epithelial cells and fibroblasts.
AB  - In the early stages of breast cancer metastasis, epithelial cells penetrate the
      basement membrane and invade the surrounding stroma, where they encounter
      fibroblasts. Paracrine signaling between fibroblasts and epithelial tumor cells
      contributes to the metastatic cascade, but little is known about the role of
      adhesive contacts between these two cell types in metastasis. Here we show that
      MCF-7 breast cancer epithelial cells and normal breast fibroblasts form
      heterotypic adhesions when grown together in co-culture, as evidenced by adhesion
      assays. PCR and immunoblotting show that both cell types express multiple members
      of the cadherin superfamily, including the atypical cadherin, cadherin-23, when
      grown in isolation and in co-culture. Immunocytochemistry experiments show that
      cadherin-23 localizes to homotypic adhesions between MCF-7 cells and also to
      heterotypic adhesions between the epithelial cells and fibroblasts, and antibody
      inhibition and RNAi experiments show that cadherin-23 plays a role in mediating
      these adhesive interactions. Finally, we show that cadherin-23 is upregulated in
      breast cancer tissue samples, and we hypothesize that heterotypic adhesions
      mediated by this atypical cadherin may play a role in the early stages of
      metastasis.

PMID- 22413012
TI  - Pervasive growth reduction in Norway spruce forests following wind disturbance.
AB  - BACKGROUND: In recent decades the frequency and severity of natural disturbances
      by e.g., strong winds and insect outbreaks has increased considerably in many
      forest ecosystems around the world. Future climate change is expected to further
      intensify disturbance regimes, which makes addressing disturbances in ecosystem
      management a top priority. As a prerequisite a broader understanding of
      disturbance impacts and ecosystem responses is needed. With regard to the effects
      of strong winds--the most detrimental disturbance agent in Europe--monitoring and
      management has focused on structural damage, i.e., tree mortality from uprooting
      and stem breakage. Effects on the functioning of trees surviving the storm (e.g.,
      their productivity and allocation) have been rarely accounted for to date.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we show that growth reduction was
      significant and pervasive in a 6.79 million hectare forest landscape in southern
      Sweden following the storm Gudrun (January 2005). Wind-related growth reduction
      in Norway spruce (Picea abies (L.) Karst.) forests surviving the storm exceeded
      10% in the worst hit regions, and was closely related to maximum gust wind speed
      (R(2) = 0.849) and structural wind damage (R(2) = 0.782). At the landscape scale,
      wind-related growth reduction amounted to 3.0 million m(3) in the three years
      following Gudrun. It thus exceeds secondary damage from bark beetles after Gudrun
      as well as the long-term average storm damage from uprooting and stem breakage in
      Sweden. CONCLUSIONS/SIGNIFICANCE: We conclude that the impact of strong winds on
      forest ecosystems is not limited to the immediately visible area of structural
      damage, and call for a broader consideration of disturbance effects on ecosystem
      structure and functioning in the context of forest management and climate change
      mitigation.

PMID- 22413013
TI  - Parvovirus b19 DNA CpG dinucleotide methylation and epigenetic regulation of
      viral expression.
AB  - CpG DNA methylation is one of the main epigenetic modifications playing a role in
      the control of gene expression. For DNA viruses whose genome has the ability to
      integrate in the host genome or to maintain as a latent episome, a correlation
      has been found between the extent of DNA methylation and viral quiescence. No
      information is available for Parvovirus B19, a human pathogenic virus, which is
      capable of both lytic and persistent infections. Within Parvovirus B19 genome,
      the inverted terminal regions display all the characteristic signatures of a
      genomic CpG island; therefore we hypothesised a role of CpG dinucleotide
      methylation in the regulation of viral genome expression.The analysis of CpG
      dinucleotide methylation of Parvovirus B19 DNA was carried out by an aptly
      designed quantitative real-time PCR assay on bisulfite-modified DNA. The effects
      of CpG methylation on the regulation of viral genome expression were first
      investigated by transfection of either unmethylated or in vitro methylated viral
      DNA in a model cell line, showing that methylation of viral DNA was correlated to
      lower expression levels of the viral genome. Then, in the course of in vitro
      infections in different cellular environments, it was observed that absence of
      viral expression and genome replication were both correlated to increasing levels
      of CpG methylation of viral DNA. Finally, the presence of CpG methylation was
      documented in viral DNA present in bioptic samples, indicating the occurrence and
      a possible role of this epigenetic modification in the course of natural
      infections.The presence of an epigenetic level of regulation of viral genome
      expression, possibly correlated to the silencing of the viral genome and
      contributing to the maintenance of the virus in tissues, can be relevant to the
      balance and outcome of the different types of infection associated to Parvovirus
      B19.

PMID- 22413014
TI  - Familial circadian rhythm disorder in the diurnal primate, Macaca mulatta.
AB  - In view of the inverse temporal relationship of central clock activity to
      physiological or behavioral outputs in diurnal and nocturnal species,
      understanding the mechanisms and physiological consequences of circadian
      disorders in humans would benefit from studies in a diurnal animal model,
      phylogenetically close to humans. Here we report the discovery of the first
      intrinsic circadian disorder in a family of diurnal non-human primates, the
      rhesus monkey. The disorder is characterized by a combination of delayed sleep
      phase, relative to light-dark cycle, mutual desynchrony of intrinsic rhythms of
      activity, food intake and cognitive performance, enhanced nighttime feeding or,
      in the extreme case, intrinsic asynchrony. The phenotype is associated with
      normal length of intrinsic circadian period and requires an intact central clock,
      as demonstrated by an SCN lesion. Entrainment to different photoperiods or
      melatonin administration does not eliminate internal desynchrony, though
      melatonin can temporarily reinstate intrinsic activity rhythms in the animal with
      intrinsic asynchrony. Entrainment to restricted feeding is highly effective in
      animals with intrinsic or SCN lesion-induced asynchrony. The large isolated
      family of rhesus macaques harboring the disorder provides a powerful new tool for
      translational research of regulatory circuits underlying circadian disorders and
      their effective treatment.

PMID- 22413015
TI  - Skeletal adaptation to intramedullary pressure-induced interstitial fluid flow is
      enhanced in mice subjected to targeted osteocyte ablation.
AB  - Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During
      mechanical loading, IFF is generated through two distinct mechanisms that result
      in spatially distinct flow profiles: poroelastic interactions within the lacunar
      canalicular system, and intramedullary pressurization. While the former generates
      IFF primarily within the lacunar-canalicular network, the latter generates
      significant flow at the endosteal surface as well as within the tissue. This
      gives rise to the intriguing possibility that loading-induced IFF may
      differentially activate osteocytes or surface-residing cells depending on the
      generating mechanism, and that sensation of IFF generated via intramedullary
      pressurization may be mediated by a non-osteocytic bone cell population. To begin
      to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation
      mouse model and a microfluidic system for modulating intramedullary pressure
      (ImP) to assess whether structural adaptation to ImP-driven IFF is altered by
      partial osteocyte depletion. Canalicular convective velocities during
      pressurization were estimated through the use of fluorescence recovery after
      photobleaching and computational modeling. Following osteocyte ablation,
      transgenic mice exhibited severe losses in bone structure and altered responses
      to hindlimb suspension in a compartment-specific manner. In pressure-loaded
      limbs, transgenic mice displayed similar or significantly enhanced structural
      adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite
      up to ~50% of trabecular lacunae being uninhabited following ablation.
      Interestingly, regression analysis revealed relative gains in bone structure in
      pressure-loaded limbs were correlated with reductions in bone structure in
      unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was
      potentiated by increases in osteoclastic activity and/or reductions in
      osteoblastic activity incurred independently of pressure loading. Collectively,
      these studies indicate that structural adaptation to ImP-driven IFF can proceed
      unimpeded following a significant depletion in osteocytes, consistent with the
      potential existence of a non-osteocytic bone cell population that senses ImP
      driven IFF independently and potentially parallel to osteocytic sensation of
      poroelasticity-derived IFF.

PMID- 22413016
TI  - A small world of citations? The influence of collaboration networks on citation
      practices.
AB  - This paper examines the proximity of authors to those they cite using degrees of
      separation in a co-author network, essentially using collaboration networks to
      expand on the notion of self-citations. While the proportion of direct self
      citations (including co-authors of both citing and cited papers) is relatively
      constant in time and across specialties in the natural sciences (10% of
      references) and the social sciences (20%), the same cannot be said for citations
      to authors who are members of the co-author network. Differences between fields
      and trends over time lie not only in the degree of co-authorship which defines
      the large-scale topology of the collaboration network, but also in the
      referencing practices within a given discipline, computed by defining a
      propensity to cite at a given distance within the collaboration network. Overall,
      there is little tendency to cite those nearby in the collaboration network,
      excluding direct self-citations. These results are interpreted in terms of small
      scale structure, field-specific citation practices, and the value of local co
      author networks for the production of knowledge and for the accumulation of
      symbolic capital. Given the various levels of integration between co-authors, our
      findings shed light on the question of the availability of 'arm's length' expert
      reviewers of grant applications and manuscripts.

PMID- 22413017
TI  - Homocysteine, grey matter and cognitive function in adults with cardiovascular
      disease.
AB  - BACKGROUND: Elevated total plasma homocysteine (tHcy) has been associated with
      cognitive impairment, vascular disease and brain atrophy. METHODS: We
      investigated 150 volunteers to determine if the association between high tHcy and
      cerebral grey matter volume and cognitive function is independent of
      cardiovascular disease. RESULTS: Participants with high tHcy (>=15 umol/L) showed
      a widespread relative loss of grey matter compared with people with normal tHcy,
      although differences between the groups were minimal once the analyses were
      adjusted for age, gender, diabetes, hypertension, smoking and prevalent
      cardiovascular disease. Individuals with high tHcy had worse cognitive scores
      across a range of domains and less total grey matter volume, although these
      differences were not significant in the adjusted models. CONCLUSIONS: Our results
      suggest that the association between high tHcy and loss of cerebral grey matter
      volume and decline in cognitive function is largely explained by increasing age
      and cardiovascular diseases and indicate that the relationship is not causal.

PMID- 22413018
TI  - The effects of hydrogen peroxide on the circadian rhythms of Microcystis
      aeruginosa.
AB  - BACKGROUND: The cyanobacterium Microcystis aeruginosa is one of the principal
      bloom-forming cyanobacteria present in a wide range of freshwater ecosystems. M.
      aeruginosa produces cyanotoxins, which can harm human and animal health. Many
      metabolic pathways in M. aeruginosa, including photosynthesis and microcystin
      synthesis, are controlled by its circadian rhythms. However, whether xenobiotics
      affect the cyanobacterial circadian system and change its growth, physiology and
      biochemistry is unknown. We used real-time PCR to study the effect of hydrogen
      peroxide (H(2)O(2)) on the expression of clock genes and some circadian genes in
      M. aeruginosa during the light/dark (LD) cycle. RESULTS: The results revealed
      that H(2)O(2) changes the expression patterns of clock genes (kaiA, kaiB, kaiC
      and sasA) and significantly decreases the transcript levels of kaiB, kaiC and
      sasA. H(2)O(2) treatment also decreased the transcription of circadian genes,
      such as photosynthesis-related genes (psaB, psbD1 and rbcL) and microcystin
      related genes (mcyA, mcyD and mcyH), and changed their circadian expression
      patterns. Moreover, the physiological functions of M. aeruginosa, including its
      growth and microcystin synthesis, were greatly influenced by H(2)O(2) treatment
      during LD. These results indicate that changes in the cyanobacterial circadian
      system can affect its physiological and metabolic pathways. CONCLUSION: Our
      findings show that a xenobiotic can change the circadian expression patterns of
      its clock genes to influence clock-controlled gene regulation, and these
      influences are evident at the level of cellular physiology.

PMID- 22413019
TI  - A disintegrin and metalloenzyme (ADAM) 17 activation is regulated by alpha5beta1
      integrin in kidney mesangial cells.
AB  - BACKGROUND: The disintegrin and metalloenzyme ADAM17 participates in numerous
      inflammatory and proliferative diseases, and its pathophysiological role was
      implicated in kidney fibrosis, polycystic kidney disease and other chronic kidney
      diseases. At present, we have little understanding how the enzyme activity is
      regulated. In this study we wanted to characterize the role of alpha5beta1
      integrin in ADAM17 activity regulation during G protein-coupled receptor (GPCR)
      stimulation. METHODOLOGY/PRINCIPAL FINDINGS: We showed previously that the
      profibrotic GPCR agonist serotonin (5-HT) induced kidney mesangial cell
      proliferation through ADAM17 activation and heparin-binding epidermal growth
      factor (HB-EGF) shedding. In the present studies we observed that in unstimulated
      mesangial cell lysates alpha5beta1 integrin co-precipitated with ADAM17 and that
      5-HT treatment of the cells induced dissociation of alpha5beta1 integrin from
      ADAM17. Using fluorescence immunostaining and in situ proximity ligation assay,
      we identified the perinuclear region as the localization of the
      ADAM17/alpha5beta1 integrin interaction. In cell-free assays, we showed that
      purified alpha5beta1 integrin and beta1 integrin dose-dependently bound to and
      inhibited activity of recombinant ADAM17. We provided evidence that the
      conformation of the integrin determines its ADAM17-binding ability. To study the
      effect of beta1 integrin on ADAM17 sheddase activity, we employed alkaline
      phosphatase-tagged HB-EGF. Overexpression of beta1 integrin lead to complete
      inhibition of 5-HT-induced HB-EGF shedding and silencing beta1 integrin by siRNA
      significantly increased mesangial cells ADAM17 responsiveness to 5-HT.
      CONCLUSIONS/SIGNIFICANCE: Our data show for the first time that beta1 integrin
      has an important physiological role in ADAM17 activity regulation. We suggest
      that regulating alpha5beta1 integrin binding to ADAM17 could be an attractive
      therapeutic target in chronic kidney diseases.

PMID- 22413020
TI  - Preserving and using germplasm and dissociated embryonic cells for conserving
      Caribbean and Pacific coral.
AB  - Coral reefs are experiencing unprecedented degradation due to human activities,
      and protecting specific reef habitats may not stop this decline, because the most
      serious threats are global (i.e., climate change), not local. However, ex situ
      preservation practices can provide safeguards for coral reef conservation.
      Specifically, modern advances in cryobiology and genome banking could secure
      existing species and genetic diversity until genotypes can be introduced into
      rehabilitated habitats. We assessed the feasibility of recovering viable sperm
      and embryonic cells post-thaw from two coral species, Acropora palmata and Fungia
      scutaria that have diffferent evolutionary histories, ecological niches and
      reproductive strategies. In vitro fertilization (IVF) of conspecific eggs using
      fresh (control) spermatozoa revealed high levels of fertilization (>90% in A.
      palmata; >84% in F. scutaria; P>0.05) that were unaffected by tested sperm
      concentrations. A solution of 10% dimethyl sulfoxide (DMSO) at cooling rates of
      20 to 30 degrees C/min most successfully cryopreserved both A. palmata and F.
      scutaria spermatozoa and allowed producing developing larvae in vitro. IVF
      success under these conditions was 65% in A. palmata and 53% in F. scutaria on
      particular nights; however, on subsequent nights, the same process resulted in
      little or no IVF success. Thus, the window for optimal freezing of high quality
      spermatozoa was short (~5 h for one night each spawning cycle). Additionally,
      cryopreserved F. scutaria embryonic cells had~50% post-thaw viability as measured
      by intact membranes. Thus, despite some differences between species, coral
      spermatozoa and embryonic cells are viable after low temperature (-196 degrees C)
      storage, preservation and thawing. Based on these results, we have begun
      systematically banking coral spermatozoa and embryonic cells on a large-scale as
      a support approach for preserving existing bio- and genetic diversity found in
      reef systems.

PMID- 22413021
TI  - PTEN as a prognostic and predictive marker in postoperative radiotherapy for
      squamous cell cancer of the head and neck.
AB  - BACKGROUND: Tumor suppressor PTEN is known to control a variety of processes
      related to cell survival, proliferation, and growth. PTEN expression is
      considered as a prognostic factor in some human neoplasms like breast, prostate,
      and thyroid cancer. METHODOLOGY/PRINCIPAL FINDINGS: In this study we analyzed the
      influence of PTEN expression on the outcome of a randomized clinical trial of
      conventional versus 7-days-a-week postoperative radiotherapy for squamous cell
      cancer of the head and neck. The patients with cancer of the oral cavity,
      oropharynx, and larynx were randomized to receive 63 Gy in fractions of 1.8 Gy
      given 5 days a week (CF) or 7 days a week (p-CAIR). Out of 279 patients enrolled
      in the study, 147 paraffin blocks were available for an immunohistochemical
      assessment of PTEN. To evaluate the prognostic value of PTEN expression and the
      effect of fractionation relative to PTEN, the data on the outcome of a randomized
      clinical trial were analyzed. Tumors with a high intensity of PTEN staining had
      significant gain in the loco-regional control (LRC) from p-CAIR (5-year LRC 92.7%
      vs. 70.8%, for p-CAIR vs. CF, p = 0.016, RR = 0.26). By contrast, tumors with low
      intensity of PTEN did not gain from p-CAIR (5-year LRC 56.2% vs. 47.2%, p = 0.49,
      RR = 0.94). The intensity of PTEN highly affected the LRC in a whole group of 147
      patients (5-year LRC 80.9% vs. 52.3% for high vs. low PTEN, p = 0.0007, RR =
      0.32). In multivariate Cox analysis, including neck node involvement, EGFR, nm23,
      Ki-67, p53, cyclin D1, tumor site and margins, PTEN remained an independent
      predictor of LRC (RR = 2.8 p = 0.004). CONCLUSIONS/SIGNIFICANCE: These results
      suggest that PTEN may serve as a potent prognostic and predictive marker in
      postoperative radiotherapy for high-risk squamous cell cancer of the head and
      neck.

PMID- 22413022
TI  - Cellular immunity confers transient protection in experimental Buruli ulcer
      following BCG or mycolactone-negative Mycobacterium ulcerans vaccination.
AB  - BACKGROUND: Buruli ulcer (BU) is an emerging infectious disease caused by
      Mycobacterium ulcerans that can result in extensive necrotizing cutaneous lesions
      due to the cytotoxic exotoxin mycolactone. There is no specific vaccine against
      BU but reports show some degree of cross-reactive protection conferred by M.
      bovis BCG immunization. Alternatively, an M. ulcerans-specific immunization could
      be a better preventive strategy. METHODOLOGY/PRINCIPAL FINDINGS: In this study,
      we used the mouse model to characterize the histological and cytokine profiles
      triggered by vaccination with either BCG or mycolactone-negative M. ulcerans,
      followed by footpad infection with virulent M. ulcerans. We observed that BCG
      vaccination significantly delayed the onset of M. ulcerans growth and footpad
      swelling through the induction of an earlier and sustained IFN-gamma T cell
      response in the draining lymph node (DLN). BCG vaccination also resulted in cell
      mediated immunity (CMI) in M. ulcerans-infected footpads, given the predominance
      of a chronic mononuclear infiltrate positive for iNOS, as well as increased and
      sustained levels of IFN-gamma and TNF. No significant IL-4, IL-17 or IL-10
      responses were detected in the footpad or the DLN, in either infected or
      vaccinated mice. Despite this protective Th1 response, BCG vaccination did not
      avoid the later progression of M. ulcerans infection, regardless of challenge
      dose. Immunization with mycolactone-deficient M. ulcerans also significantly
      delayed the progression of footpad infection, swelling and ulceration, but
      ultimately M. ulcerans pathogenic mechanisms prevailed. CONCLUSIONS/SIGNIFICANCE:
      The delay in the emergence of pathology observed in vaccinated mice emphasizes
      the relevance of protective Th1 recall responses against M. ulcerans. In future
      studies it will be important to determine how the transient CMI induced by
      vaccination is compromised.

PMID- 22413023
TI  - Effect of methodological and ecological approaches on heterogeneity of nest-site
      selection of a long-lived vulture.
AB  - The application of scientific-based conservation measures requires that sampling
      methodologies in studies modelling similar ecological aspects produce comparable
      results making easier their interpretation. We aimed to show how the choice of
      different methodological and ecological approaches can affect conclusions in nest
      site selection studies along different Palearctic meta-populations of an
      indicator species. First, a multivariate analysis of the variables affecting nest
      site selection in a breeding colony of cinereous vulture (Aegypius monachus) in
      central Spain was performed. Then, a meta-analysis was applied to establish how
      methodological and habitat-type factors determine differences and similarities in
      the results obtained by previous studies that have modelled the forest breeding
      habitat of the species. Our results revealed patterns in nesting-habitat
      modelling by the cinereous vulture throughout its whole range: steep and south
      facing slopes, great cover of large trees and distance to human activities were
      generally selected. The ratio and situation of the studied plots (nests/random),
      the use of plots vs. polygons as sampling units and the number of years of data
      set determined the variability explained by the model. Moreover, a greater size
      of the breeding colony implied that ecological and geomorphological variables at
      landscape level were more influential. Additionally, human activities affected in
      greater proportion to colonies situated in Mediterranean forests. For the first
      time, a meta-analysis regarding the factors determining nest-site selection
      heterogeneity for a single species at broad scale was achieved. It is essential
      to homogenize and coordinate experimental design in modelling the selection of
      species' ecological requirements in order to avoid that differences in results
      among studies would be due to methodological heterogeneity. This would optimize
      best conservation and management practices for habitats and species in a global
      context.

PMID- 22413024
TI  - Distribution and molecular evolution of bacillus anthracis genotypes in Namibia.
AB  - The recent development of genetic markers for Bacillus anthracis has made it
      possible to monitor the spread and distribution of this pathogen during and
      between anthrax outbreaks. In Namibia, anthrax outbreaks occur annually in the
      Etosha National Park (ENP) and on private game and livestock farms. We genotyped
      384 B. anthracis isolates collected between 1983-2010 to identify the possible
      epidemiological correlations of anthrax outbreaks within and outside the ENP and
      to analyze genetic relationships between isolates from domestic and wild animals.
      The isolates came from 20 animal species and from the environment and were
      genotyped using a 31-marker multi-locus-VNTR-analysis (MLVA) and, in part, by
      twelve single nucleotide polymorphism (SNP) markers and four single nucleotide
      repeat (SNR) markers. A total of 37 genotypes (GT) were identified by MLVA,
      belonging to four SNP-groups. All GTs belonged to the A-branch in the cluster-
      and SNP-analyses. Thirteen GTs were found only outside the ENP, 18 only within
      the ENP and 6 both inside and outside. Genetic distances between isolates
      increased with increasing time between isolations. However, genetic distance
      between isolates at the beginning and end of the study period was relatively
      small, indicating that while the majority of GTs were only found sporadically,
      three genetically close GTs, accounting for more than four fifths of all the ENP
      isolates, appeared dominant throughout the study period. Genetic distances among
      isolates were significantly greater for isolates from different host species, but
      this effect was small, suggesting that while species-specific ecological factors
      may affect exposure processes, transmission cycles in different host species are
      still highly interrelated. The MLVA data were further used to establish a model
      of the probable evolution of GTs within the endemic region of the ENP. SNR
      analysis was helpful in correlating an isolate with its source but did not
      elucidate epidemiological relationships.

PMID- 22413025
TI  - The burden of trachoma in South Sudan: assessing the health losses from a
      condition of graded severity.
AB  - INTRODUCTION: Trachoma is a disease that can lead to visual impairment and
      ultimately blindness. Previous estimates of health losses from trachoma using the
      Global Burden of Disease methodology have not, however, included the stage prior
      to visual impairment. We estimated the burden of all stages of trachoma in South
      Sudan and assessed the uncertainty associated with the severity and duration of
      stages of trachoma prior to full blindness. METHODS: The prevalence of trachoma
      with normal vision, low vision and blindness in the Republic of South Sudan has
      been estimated previously. These estimates were used to model the incidence and
      duration of the different stages employing DISMOD II. Different assumptions about
      disability weights and duration were used to estimate the Years Lived with
      Disability (YLD). RESULTS: We have estimated the total burden of trachoma in
      South Sudan to be between 136,562 and 163,695 YLD and trichiasis with normal
      vision contributes between 5% and 21% of the total depending on the disability
      weight applied. Women experience more of this burden than men. The sensitivity of
      the results to different assumptions about the disability weights is partly
      dependent upon the assumed duration of the different disease states.
      INTERPRETATION: A better understanding of the natural history of trachoma is
      critical for a more accurate burden estimate.

PMID- 22413026
TI  - Comparison of real-time quantitative PCR and culture for the diagnosis of
      emerging Rickettsioses.
AB  - BACKGROUND: Isolation of Rickettsia species from skin biopsies may be replaced by
      PCR. We evaluated culture sensitivity compared to PCR based on sampling delay and
      previous antibiotic treatment. METHODOLOGY/PRINCIPAL FINDINGS: Skin biopsies and
      ticks from patients with suspected Rickettsia infection were screened for
      Rickettsia spp. using qPCR, and positive results were amplified and sequenced for
      the gltA and ompA genes. Immunofluorescence for spotted fever group rickettsial
      antigens was done for 79 patients. All skin biopsies and only ticks that tested
      positive using qPCR were cultured in human embryonic lung (HEL) fibroblasts using
      the centrifugation-shell vial technique. Patients and ticks were classified as
      definitely having rickettsioses if there was direct evidence of infection with a
      Rickettsia sp. using culture or molecular assays or in patients if serology was
      positive. Data on previous antibiotic treatments were obtained for patients with
      rickettsiosis. Rickettsia spp. infection was diagnosed in 47 out of 145 patients
      (32%), 41 by PCR and 12 by culture, whereas 3 isolates were obtained from PCR
      negative biopsies. For 3 of the patients serology was positive although PCR and
      culture were negative. Rickettsia africae was the most common detected species (n
      = 25, [17.2%]) and isolated bacterium (n = 5, [3.4%]). The probability of
      isolating Rickettsia spp. was 12 times higher in untreated patients and 5.4 times
      higher in patients from our hometown. Rickettsia spp. was amplified in 24 out of
      95 ticks (25%) and we isolated 7 R. slovaca and 1 R. raoultii from Dermacentor
      marginatus. CONCLUSIONS/SIGNIFICANCE: We found a positive correlation between the
      bacteria copies and the isolation success in skin biopsies and ticks. Culture
      remains critical for strain analysis but is less sensitive than serology and PCR
      for the diagnosis of a Rickettsia infection.

PMID- 22413027
TI  - Association between anaemia, iron deficiency anaemia, neglected parasitic
      infections and socioeconomic factors in rural children of West Malaysia.
AB  - BACKGROUND: Given that micronutrient deficiency, neglected intestinal parasitic
      infections (IPIs) and poor socioeconomic status are closely linked, we conducted
      a cross-sectional study to assess the relationship between IPIs and nutritional
      status of children living in remote and rural areas in West Malaysia.
      METHODS/FINDINGS: A total of 550 children participated, comprising 520 (94.5%)
      school children aged 7 to 12 years old, 30 (5.5%) young children aged 1 to 6
      years old, 254 (46.2%) boys and 296 (53.8%) girls. Of the 550 children, 26.2%
      were anaemic, 54.9% iron deficient and 16.9% had iron deficiency anaemia (IDA).
      The overall prevalence of helminths was 76.5% comprising Trichuris trichiura
      (71.5%), Ascaris lumbricoides (41.6%) and hookworm infection (13.5%). It was
      observed that iron deficiency was significantly higher in girls (p = 0.032)
      compared to boys. Univariate analysis demonstrated that low level of mother's
      education (OR = 2.52; 95% CI = 1.38-4.60; p = 0.002), non working parents (OR =
      2.18; 95% CI = 2.06-2.31; p = 0.013), low household income (OR = 2.02; 95% CI =
      1.14-3.59; p = 0.015), T. trichiura (OR = 2.15; 95% CI = 1.21-3.81; p = 0.008)
      and A. lumbricoides infections (OR = 1.63; 95% CI = 1.04-2.55; p = 0.032) were
      significantly associated with the high prevalence of IDA. Multivariate analysis
      confirmed that low level of mother's education (OR = 1.48; 95 CI% = 1.33-2.58;
      p<0.001) was a significant predictor for IDA in these children. CONCLUSION: It is
      crucial that a comprehensive primary health care programme for these communities
      that includes periodic de-worming, nutrition supplement, improved household
      economy, education, sanitation status and personal hygiene are taken into
      consideration to improve the nutritional status of these children.

PMID- 22413028
TI  - Echinococcus granulosus antigen B structure: subunit composition and oligomeric
      states.
AB  - BACKGROUND: Antigen B (AgB) is the major protein secreted by the Echinococcus
      granulosus metacestode and is involved in key host-parasite interactions during
      infection. The full comprehension of AgB functions depends on the elucidation of
      several structural aspects that remain unknown, such as its subunit composition
      and oligomeric states. METHODOLOGY/PRINCIPAL FINDINGS: The subunit composition of
      E. granulosus AgB oligomers from individual bovine and human cysts was assessed
      by mass spectrometry associated with electrophoretic analysis. AgB8/1, AgB8/2,
      AgB8/3 and AgB8/4 subunits were identified in all samples analyzed, and an AgB8/2
      variant (AgB8/2v8) was found in one bovine sample. The exponentially modified
      protein abundance index (emPAI) was used to estimate the relative abundance of
      the AgB subunits, revealing that AgB8/1 subunit was relatively overrepresented in
      all samples. The abundance of AgB8/3 subunit varied between bovine and human
      cysts. The oligomeric states formed by E. granulosus AgB and recombinant subunits
      available, rAgB8/1, rAgB8/2 and rAgB8/3, were characterized by native PAGE, light
      scattering and microscopy. Recombinant subunits showed markedly distinct
      oligomerization behaviors, forming oligomers with a maximum size relation of
      rAgB8/3>rAgB8/2>rAgB8/1. Moreover, the oligomeric states formed by rAgB8/3
      subunit were more similar to those observed for AgB purified from hydatid fluid.
      Pressure-induced dissociation experiments demonstrated that the molecular
      assemblies formed by the more aggregative subunits, rAgB8/2 and rAgB8/3, also
      display higher structural stability. CONCLUSIONS/SIGNIFICANCE: For the first
      time, AgB subunit composition was analyzed in samples from single hydatid cysts,
      revealing qualitative and quantitative differences between samples. We showed
      that AgB oligomers are formed by different subunits, which have distinct
      abundances and oligomerization properties. Overall, our findings have
      significantly contributed to increase the current knowledge on AgB expression and
      structure, highlighting issues that may help to understand the parasite adaptive
      response during chronic infection.

PMID- 22413029
TI  - Mapping of schistosomiasis and soil-transmitted helminthiasis in the regions of
      centre, East and West Cameroon.
AB  - BACKGROUND: Schistosomiasis and soil-transmitted helminthiasis (STH) are widely
      distributed in Cameroon. Although mass drug administration (MDA) of mebendazole
      is implemented nationwide, treatment with praziquantel was so far limited to the
      three northern regions and few health districts in the southern part of Cameroon,
      based on previous mapping conducted 25 years ago. To update the disease
      distribution map and determine where treatment with praziquantel should be
      extended, mapping surveys were conducted in three of the seven southern regions
      of Cameroon, i.e. Centre, East and West. METHODOLOGY: Parasitological surveys
      were conducted in April-May 2010 in selected schools in all 63 health districts
      of the three targeted regions, using appropriate research methodologies, i.e.
      Kato-Katz and urine filtration. PRINCIPAL FINDINGS: The results showed
      significant variation of schistosomiasis and STH prevalence between schools,
      villages, districts and regions. Schistosoma mansoni was the most prevalent
      schistosome species, with an overall prevalence of 5.53%, followed by S.
      haematobium (1.72%) and S. guineensis (0.14%). The overall prevalence of
      schistosomiasis across the three regions was 7.31% (95% CI: 6.86-7.77%). The
      prevalence for Ascaris lumbricoides was 11.48 (95% CI: 10.93-12.04%), Trichuris
      trichiura 18.22% (95% CI: 17.56-18.90%) and hookworms 1.55% (95% CI: 1.35-1.78%),
      with an overall STH prevalence of 24.10% (95% CI: 23.36-24.85%) across the three
      regions. STH was more prevalent in the East region (46.57%; 95% CI: 44.41-48.75%)
      in comparison to the Centre (25.12; 95% CI: 24.10-26.17%) and West (10.49%; 95%
      CI: 9.57-11.51%) regions. CONCLUSIONS/SIGNIFICANCE: In comparison to previous
      data, the results showed an increase of schistosomiasis transmission in several
      health districts, whereas there was a significant decline of STH infections.
      Based on the prevalence data, the continuation of annual or bi-annual MDA for STH
      is recommended, as well as an extension of praziquantel in identified moderate
      and high risk communities for schistosomiasis.

PMID- 22413030
TI  - Bacterial diversity in oral samples of children in niger with acute noma, acute
      necrotizing gingivitis, and healthy controls.
AB  - BACKGROUND: Noma is a gangrenous disease that leads to severe disfigurement of
      the face with high morbidity and mortality, but its etiology remains unknown.
      Young children in developing countries are almost exclusively affected. The
      purpose of the study was to record and compare bacterial diversity in oral
      samples from children with or without acute noma or acute necrotizing gingivitis
      from a defined geographical region in Niger by culture-independent molecular
      methods. METHODS AND PRINCIPAL FINDINGS: Gingival samples from 23 healthy
      children, nine children with acute necrotizing gingivitis, and 23 children with
      acute noma (both healthy and diseased oral sites) were amplified using
      "universal" PCR primers for the 16 S rRNA gene and pooled according to category
      (noma, healthy, or acute necrotizing gingivitis), gender, and site status
      (diseased or control site). Seven libraries were generated. A total of 1237
      partial 16 S rRNA sequences representing 339 bacterial species or phylotypes at a
      98-99% identity level were obtained. Analysis of bacterial composition and
      frequency showed that diseased (noma or acute necrotizing gingivitis) and healthy
      site bacterial communities are composed of similar bacteria, but differ in the
      prevalence of a limited group of phylotypes. Large increases in counts of
      Prevotella intermedia and members of the Peptostreptococcus genus are associated
      with disease. In contrast, no clear-cut differences were found between noma and
      non-noma libraries. CONCLUSIONS: Similarities between acute necrotizing
      gingivitis and noma samples support the hypothesis that the disease could evolve
      from acute necrotizing gingivitis in certain children for reasons still to be
      elucidated. This study revealed oral microbiological patterns associated with
      noma and acute necrotizing gingivitis, but no evidence was found for a specific
      infection-triggering agent.

PMID- 22413031
TI  - Immunization with L. sigmodontis microfilariae reduces peripheral microfilaraemia
      after challenge infection by inhibition of filarial embryogenesis.
AB  - BACKGROUND: Lymphatic filariasis and onchocerciasis are two chronic diseases
      mediated by parasitic filarial worms causing long term disability and massive
      socioeconomic problems. Filariae are transmitted by blood-feeding mosquitoes that
      take up the first stage larvae from an infected host and deliver it after
      maturation into infective stage to a new host. After closure of vector control
      programs, disease control relies mainly on mass drug administration with drugs
      that are primarily effective against first stage larvae and require many years of
      annual/biannual administration. Therefore, there is an urgent need for
      alternative treatment ways, i.e. other effective drugs or vaccines.
      METHODOLOGY/PRINCIPAL FINDINGS: Using the Litomosoides sigmodontis murine model
      of filariasis we demonstrate that immunization with microfilariae together with
      the adjuvant alum prevents mice from developing high microfilaraemia after
      challenge infection. Immunization achieved 70% to 100% protection in the
      peripheral blood and in the pleural space and furthermore strongly reduced the
      microfilarial load in mice that remained microfilaraemic. Protection was
      associated with the impairment of intrauterine filarial embryogenesis and with
      local and systemic microfilarial-specific host IgG, as well as IFN-gamma
      secretion by host cells from the site of infection. Furthermore immunization
      significantly reduced adult worm burden. CONCLUSIONS/SIGNIFICANCE: Our results
      present a tool to understand the immunological basis of vaccine induced
      protection in order to develop a microfilariae-based vaccine that reduces adult
      worm burden and prevents microfilaraemia, a powerful weapon to stop transmission
      of filariasis.

PMID- 22413032
TI  - Reciprocal tripartite interactions between the Aedes aegypti midgut microbiota,
      innate immune system and dengue virus influences vector competence.
AB  - Dengue virus is one of the most important arboviral pathogens and the causative
      agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. It is
      transmitted between humans by the mosquitoes Aedes aegypti and Aedes albopictus,
      and at least 2.5 billion people are at daily risk of infection. During their
      lifecycle, mosquitoes are exposed to a variety of microbes, some of which are
      needed for their successful development into adulthood. However, recent studies
      have suggested that the adult mosquito's midgut microflora is critical in
      influencing the transmission of human pathogens. In this study we assessed the
      reciprocal interactions between the mosquito's midgut microbiota and dengue virus
      infection that are, to a large extent, mediated by the mosquito's innate immune
      system. We observed a marked decrease in susceptibility to dengue virus infection
      when mosquitoes harbored certain field-derived bacterial isolates in their
      midgut. Transcript abundance analysis of selected antimicrobial peptide genes
      suggested that the mosquito's microbiota elicits a basal immune activity that
      appears to act against dengue virus infection. Conversely, the elicitation of the
      mosquito immune response by dengue virus infection itself influences the
      microbial load of the mosquito midgut. In sum, we show that the mosquito's
      microbiota influences dengue virus infection of the mosquito, which in turn
      activates its antibacterial responses.

PMID- 22413033
TI  - Early clinical features of dengue virus infection in nicaraguan children: a
      longitudinal analysis.
AB  - BACKGROUND: Tens of millions of dengue cases and approximately 500,000 life
      threatening complications occur annually. New tools are needed to distinguish
      dengue from other febrile illnesses. In addition, the natural history of
      pediatric dengue early in illness in a community-based setting has not been well
      defined. METHODS: Data from the multi-year, ongoing Pediatric Dengue Cohort Study
      of approximately 3,800 children aged 2-14 years in Managua, Nicaragua, were used
      to examine the frequency of clinical signs and symptoms by day of illness and to
      generate models for the association of signs and symptoms during the early phase
      of illness and over the entire course of illness with testing dengue-positive.
      Odds ratios (ORs) and 95% confidence intervals were calculated using generalized
      estimating equations (GEE) for repeated measures, adjusting for age and gender.
      RESULTS: One-fourth of children who tested dengue-positive did not meet the WHO
      case definition for suspected dengue. The frequency of signs and symptoms varied
      by day of illness, dengue status, and disease severity. Multivariable GEE models
      showed increased odds of testing dengue-positive associated with fever, headache,
      retro-orbital pain, myalgia, arthralgia, rash, petechiae, positive tourniquet
      test, vomiting, leukopenia, platelets <=150,000 cells/mL, poor capillary refill,
      cold extremities and hypotension. Estimated ORs tended to be higher for signs and
      symptoms over the course of illness compared to the early phase of illness.
      CONCLUSIONS: Day-by-day analysis of clinical signs and symptoms together with
      longitudinal statistical analysis showed significant associations with testing
      dengue-positive and important differences during the early phase of illness
      compared to the entire course of illness. These findings stress the importance of
      considering day of illness when developing prediction algorithms for real-time
      clinical management.

PMID- 22413034
TI  - Suppression of oxidative stress by grape seed supplementation in rats.
AB  - Polyphenol-rich grape seeds have a beneficial effect on human health. The present
      study was performed to investigate the effects of grape seeds on antioxidant
      activities in rats. Male Sprague-Dawley rats were randomly divided into a control
      diet group (C), a high-fat diet group (HF), a 5% grape seed-supplemented control
      diet group (G), and a 5% grape seed-supplemented high-fat diet group (HG).
      Dietary supplementation with grape seeds reduced serum concentrations of lipid
      peroxides compared with those in the C and HF groups. The hepatic level of lipid
      peroxides decreased significantly in the grape seed groups compared with that in
      the C and HF groups. Superoxide dismutase activity in the G group increased
      significantly compared with that in the C group. Catalase activity tended to be
      higher by feeding grape seeds. The grape seed diet increased glutathione
      peroxidase activity in the C group. Glutathione-S-transferase activity increased
      significantly in the G group compared with that in the C group. Hepatic content
      of total glutathione increased significantly in the HG group but decreased
      significantly in the HF group. The ratio of reduced glutathione and oxidized
      glutathione increased by feeding the grape seed diet. Total vitamin A
      concentration was significantly higher in HG group than in other groups. Liver
      tocopherol content of the G and HG groups was significantly higher than that of
      the control groups. These results suggest that dietary supplementation with grape
      seeds is beneficial for suppressing lipid peroxidation in high fat-fed rats.

PMID- 22413035
TI  - The effects of Angelica keiskei Koidz on the expression of antioxidant enzymes
      related to lipid profiles in rats fed a high fat diet.
AB  - This study was performed to examine the feeding effects of Angelica keiskei Koidz
      (AK) and its processed products on serum, liver, and body fat content and the
      expression of antioxidant genes in rats fed a high fat diet. AK and its processed
      products were added at 3-5% to a high fat diet and fed to adult rats for 6 weeks.
      In experiment 1 (EXP 1), the rats were fed with one of six diets including a
      control diet (normal fat), high fat diet (HF), and HF + AK additives groups (four
      groups). In experiment 2 (EXP 2), the rats were separated into three groups of
      HF, HF + AK whole leaves, and HF + fermented juice (FS) + squeeze (SA). Body
      weight was not different among the groups in either experiment. The liver weight
      was lower in the FS and SA groups compared to that in the other groups (P <
      0.05). Serum luteolin was higher in the AK and processed products groups compared
      to that in the HF group (P < 0.05). Gene expression of the antioxidative enzymes
      catalase and glutathione-s-reductase in the liver was higher in the AK processed
      products group than that in the other groups (P < 0.05). The results suggest that
      the intake of AK and its processed products increased the expression of
      antioxidant enzymes in animals fed a high fat diet, reduced hepatic cholesterol
      content, and increased the effective absorption of luteolin.

PMID- 22413037
TI  - Comparison of the chemical compositions and nutritive values of various pumpkin
      (Cucurbitaceae) species and parts.
AB  - Pumpkins have considerable variation in nutrient contents depending on the
      cultivation environment, species, or part. In this study, the general chemical
      compositions and some bioactive components, such as tocopherols, carotenoids, and
      beta-sitosterol, were analyzed in three major species of pumpkin (Cucurbitaceae
      pepo, C. moschata, and C. maxima) grown in Korea and also in three parts (peel,
      flesh, and seed) of each pumpkin species. C. maxima had significantly more
      carbohydrate, protein, fat, and fiber than C. pepo or C. moschata (P < 0.05). The
      moisture content as well as the amino acid and arginine contents in all parts of
      the pumpkin was highest in C. pepo. The major fatty acids in the seeds were
      palmitic, stearic, oleic, and linoleic acids. C. pepo and C. moschata seeds had
      significantly more gamma-tocopherol than C. maxima, whose seeds had the highest
      beta-carotene content. C. pepo seeds had significantly more beta-sitosterol than
      the others. Nutrient compositions differed considerably among the pumpkin species
      and parts. These results will be useful in updating the nutrient compositions of
      pumpkin in the Korean food composition database. Additional analyses of various
      pumpkins grown in different years and in different areas of Korea are needed.

PMID- 22413036
TI  - Effect of retrograded rice on weight control, gut function, and lipid
      concentrations in rats.
AB  - The effects of retrograded rice on body weight gain, gut functions, and
      hypolipidemic actions in rats were examined. When the retrograded rice was
      produced by repetitive heating and cooling cycles, it contained significantly
      higher amounts of resistant starch (13.9 +/- 0.98%) than is found in common rice
      (9.1 +/- 1.02%) (P < 0.05). Sprague-Dawley rats were fed either common rice
      powder or retrograded rice powder, and mean body weight gain was significantly
      lower in the retrograded rice group (P < 0.05). The liver weight of the
      retrograded rice group (14.5 +/- 0.5 g) was significantly lower than that of the
      common rice group (17.1 +/- 0.3 g, P < 0.05). However, the weights of other
      organs, such as the kidney, spleen, thymus, and epididymal fat pad were not
      significantly affected by rice feeding. Intestinal transit time tended to be
      lower in rats fed retrograded rice when compared to rats fed the common rice, but
      the difference was not significant. The retrograded rice diet significantly
      increased stool output when compared to that in the common rice powder diet (P <
      0.05), whereas fecal moisture content (%) was significantly higher in the
      retrograded rice group (23.3 +/- 1.2) than that in the common rice group (19.1 +/
      1.2) (P < 0.05). The retrograded rice group had significantly lower plasma
      cholesterol (P < 0.05), liver cholesterol (P < 0.05), and triacylglycerol
      contents in adipose tissue (P < 0.05) when compared to those in the common rice
      group. In conclusion, retrograded rice had higher resistant starch levels
      compared with those of common rice powder, and it lowered body weight gain and
      improved lipid profiles and gut function in rats.

PMID- 22413038
TI  - Analysis of dietary insoluble and soluble fiber contents in school meal.
AB  - The objective of this study was to estimate the contents of dietary insoluble and
      soluble fiber in school meal. Samples of the school meals were collected from May
      to June in 2008. Three elementary schools and three middle schools around Masan
      area were selected for analysis. Dietary soluble and insoluble fibers in the
      school meals were analyzed directly by the AOAC method. From the initial
      experiment phase, we used cellulose and pectin as a standard of dietary fiber,
      and average recovery rate of insoluble fiber and soluble fiber was calculated.
      The recovery rate was observed, the cellulose 109.7+/-11.7% (range 90~150%) and
      pectin 77.8+/-10.8% (range 64.7~96.7%), respectively. The amounts of insoluble
      fiber and soluble fiber were analyzed in the total of 66 dishes, which included 7
      kinds of cooked rice (bab) made with some cereal products and vegetables, 19
      kinds of soup (guk) made with meats or vegetables, 11 kinds of kimchi, 21 kinds
      of entrees or side dishes, and 8 special dishes. Conclusively the school meal,
      per serving size, would provide above 75% KDRI of total dietary fibers through
      mainly soups and special menu, with the exception to fruits. In addition, it
      might be expected that children could consume more soluble fiber from the meals
      with the special dishes than from the regular ones.

PMID- 22413039
TI  - The effect of a nutritional education program on the nutritional status of
      elderly patients in a long-term care hospital in Jeollanamdo province: health
      behavior, dietary behavior, nutrition risk level and nutrient intake.
AB  - This study was conducted to assess improvements in nutritional status following
      the application of nutrition education to elderly patients in a long-term care
      hospital. The study was carried out from January to May 2009, during which a
      preliminary survey, a pretest, the application of nutrition education, and a post
      test were applied in stages. The number of subjects at pretest was 81, and the
      number of participants included in the final analysis was 61 (18 men, 43 women),
      all of whom participated in both the nutrition education program and the post
      test. The survey consisted of general demographic items, health behaviors,
      dietary behaviors, the Nutrition Screening Initiative checklist, and nutrient
      intake assessment (24 hour recall method). The nutrition education program lasted
      for four weeks. It included a basic education program, provided once a week, and
      mini-education program, which was offered daily during lunch times. The survey
      was conducted before and after the education program using the same assessment
      method, although some items were included only at pretest. When analyzing the
      changes in elderly patients after the nutritional education program, we found
      that, among subjective dietary behaviors, self-rated perceptions of health (P <
      0.001) and of depression (P < 0.001) improved significantly and that dietary
      behavior scores also improved significantly (P < 0.001), while nutritional risk
      levels decreased. In terms of nutrient intake, subjects' intake of energy,
      protein, fat, carbohydrate, calcium, phosphorus, iron, vitamin A, thiamin,
      riboflavin, niacin, and vitamin C all increased significantly (P < 0.001). These
      results indicated that nutritional education is effective in improving the
      nutritional status of elderly patients. We hope that the results of this study
      can be used as preliminary data for establishing guidelines for nutrition
      management tailored to elderly patients in long-term care hospitals.

PMID- 22413040
TI  - Vitamin A status of 20- to 59-year-old adults living in Seoul and the
      metropolitan area, Korea.
AB  - Dietary intakes and plasma concentrations of retinol and carotenoids were
      estimated in assessing the vitamin A status of Korean adults living in Seoul and
      the metropolitan area. Three consecutive 24-h food recalls were collected from
      106 healthy subjects (33 males and 73 females) aged 20-59 years. Fasting blood
      samples of the subjects were obtained and plasma retinol and carotenoids were
      analyzed. The daily vitamin A intakes (mean +/- SD) were 887.77 +/- 401.35 ug
      retinol equivalents or 531.84 +/- 226.42 ug retinol activity equivalents. There
      were no significant differences in vitamin A intakes among age groups. The
      retinol intake of subjects was 175.92 +/- 129.87 ug/day. The retinol intake of
      the subjects in their 50's was significantly lower than those in their 20's and
      30's (P < 0.05). Provitamin A carotenoid intakes were 3,828.37 +/- 2,196.29
      ug/day beta-carotene, 472.57 +/- 316.68 ug/day alpha-carotene, and 412.83 +/-
      306.46 ug/day beta-cryptoxanthin. Approximately 17% of the subjects consumed
      vitamin A less than the Korean Estimated Average Requirements for vitamin A. The
      plasma retinol concentration was 1.22 +/- 0.34 umol/L. There was no significant
      difference in plasma retinol concentrations among age groups. However, the
      concentrations of beta-carotene, lycopene, and lutein of subjects in their 50's
      were significantly higher than those of in their 20's. Only one subject had a
      plasma retinol concentration < 0.70 umol/L indicating marginal vitamin A status.
      Plasma retinol concentration in 30% of the subjects was 0.70- < 1.05 umol/L,
      which is interpreted as the concentration possibly responsive to greater intake
      of vitamin A. In conclusion, dietary intakes and status of vitamin A were
      generally adequate in Korean adults examined in this study.

PMID- 22413041
TI  - Accuracy of predictive equations for resting energy expenditure (REE) in non
      obese and obese Korean children and adolescents.
AB  - Weight-controlling can be supported by a proper prescription of energy intake.
      The individual energy requirement is usually determined through resting energy
      expenditure (REE) and physical activity. Because REE contributes to 60-70% of
      daily energy expenditure, the assessment of REE is very important. REE is often
      predicted using various equations, which are usually based on the body weight,
      height, age, gender, and so on. The aim of this study is to validate the
      published predictive equations for resting energy expenditure in 76 normal weight
      and 52 obese Korean children and adolescents in the 7-18 years old age group. The
      open-circuit indirect calorimetry using a ventilated hood system was used to
      measure REE. Sixteen REE predictive equations were included, which were based on
      weight and/or height of children and adolescents, or which were commonly used in
      clinical settings despite its use based on adults. The accuracy of the equations
      was evaluated on bias, RMSPE, and percentage of accurate prediction. The means of
      age and height were not significantly different among the groups. Weight and BMI
      were significantly higher in obese group (64.0 kg, 25.9 kg/m(2)) than in the non
      obese group (44.8 kg, 19.0 kg/m(2)). For the obese group, the Molnar, Mifflin,
      Liu, and Harris-Benedict equations provided the accurate predictions of > 70%
      (87%, 79% 77%, and 73%, respectively). On the other hand, for non-obese group,
      only the Molnar equation had a high level of accuracy (bias of 0.6%, RMSPE of
      90.4 kcal/d, and accurate prediction of 72%). The accurate prediction of the
      Schofield (W/WH), WHO (W/WH), and Henry (W/WH) equations was less than 60% for
      all groups. Our results showed that the Molnar equation appears to be the most
      accurate and precise for both the non-obese and the obese groups. This equation
      might be useful for clinical professionals when calculating energy needs in
      Korean children and adolescents.

PMID- 22413042
TI  - Breakfast patterns are associated with metabolic syndrome in Korean adults.
AB  - The Korean diet, including breakfast, is becoming more Western, which could
      increase the risk of metabolic syndrome. Our aim was to assess whether breakfast
      patterns are associated with risk for metabolic syndrome in Korean adults. The
      study subjects (n = 371; 103 men, 268 women) were employees of Jaesang Hospital
      in Korea and their acquaintances, and all subjects were between 30 and 50 years
      old. The data collected from each subject included anthropometric measurements,
      three-day food intake, blood pressure (BP) and blood analyses. The three
      breakfast patterns identified by factor analysis were "Rice, Kimchi and
      Vegetables", "Potatoes, Fruits and Nuts" and "Eggs, Breads and Processed meat".
      The "Rice, Kimchi and Vegetables" pattern scores were positively correlated with
      systolic (SBP) and diastolic blood pressure (DBP) measurements in men (P < 0.05)
      and with serum triglyceride (TG) levels in women (P < 0.05). The "Eggs, Breads
      and Processed meat" pattern scores correlated positively with weight, body mass
      index (P < 0.05) and serum TGs (P < 0.01) in men. The "Potatoes, Fruits and Nuts"
      pattern was associated with lower risk of elevated BP (OR 0.49, 95% CI 0.28-0.88)
      and fasting glucose levels (OR 0.51, 95% CI 0.26-1.00). In contrast, the "Eggs,
      Breads and Processed meat" pattern was associated with increased risk of elevated
      TGs (OR 2.06, 95% CI 1.06-3.98). Our results indicate that reducing the
      consumption of eggs, western grains and processed meat while increasing fruit,
      nut and vegetable intake for breakfast could have beneficial effects on
      decreasing metabolic syndrome risk in Korean adults.

PMID- 22413043
TI  - Dietary flavan-3-ols intake and metabolic syndrome risk in Korean adults.
AB  - Flavan-3-ols are a subclass of flavonoids found in a variety of foods including
      teas. The effects of flavan-3-ols on the risk of metabolic syndrome (MetS) have
      been investigated, generally focusing on tea catechins or individual flavan-3-ol
      rich foods, but there is little information on dietary flavan-3-ols intake and
      risk of MetS in population-based studies. In this cross-sectional study, we
      examined the association between dietary flavan-3-ols intake and the risk of MetS
      in Korean adults. Subjects comprised 1,827 men and 2,918 women aged 20-69 years
      whose data was included in the 2008 Korean National Health and Nutrition
      Examination Survey. This survey was conducted between January 2008 and December
      2008. Total flavan-3-ols intakes were calculated from 24-hour dietary recalls
      using a flavonoids database. Thirty percent of the male subjects and 24% of the
      female subjects were reported as having MetS. In the female subjects, flavan3-ols
      intake was inversely associated with the risk of MetS after adjusting for
      potential confounders (5th vs. 1st quintile, OR = 0.64, 95% CI = 0.45-0.91, P for
      trend = 0.384). The main food source of flavan-3-ols was green tea followed by
      apples and grapes. Among MetS components, flavan3-ols intake was inversely
      associated with the risk of high blood pressure after adjusting for potential
      confounders (5th vs. 1st quintile, OR = 0.64, 95% CI = 0.45-0.90, P for trend =
      0.005). No significant association between flavan-3-ols intake and risk of MetS
      was found in the male subjects. After stratified analysis by obesity (BMI >= 25
      or BMI < 25), however, flavan3-ols intake was inversely related to the risk of
      hypertension in non-obese men. These results suggest that dietary flavan-3-ols
      intake may have beneficial effects on MetS risk by reducing the risk of
      hypertension. The effects of flavan-3-ols intake dependent on obesity need
      further investigation.

PMID- 22413045
TI  - Sex-specific relationships between alcohol consumption and vitamin D levels: The
      Korea National Health and Nutrition Examination Survey 2009.
AB  - This study assessed the association between vitamin D sufficiency (serum 25(OH)D
      >=30 ng/mL) and alcohol consumption using data from the Korea National Health and
      Nutrition Examination Survey conducted in 2009. The following characteristics
      were obtained in 7,010 Korean participants >=19-years-of-age: serum 25(OH)D
      level, alcohol consumption (drinking frequency, drinking number of alcoholic
      beverages on a typical occasion, average daily-alcohol intake), and potential
      confounders (age, residence, housing status, occupation, total fat and lean mass,
      smoking, physical activity, history of liver diseases, liver function, and daily
      intake of energy, protein, and calcium). After adjusting for confounders, vitamin
      D sufficiency in men was significantly associated with drinking frequency, number
      of alcoholic drinks consumed, and average daily alcohol intake; odds ratio of
      1.21-1.72, 2.17-3.04, and 2.27-3.09, respectively. Increase in the three alcohol
      drinking-related behaviors was also linearly associated with increase in serum
      25(OH)D level in men. By comparison, there was no significant association between
      alcohol intake and serum 25(OH)D level in women. The positive association between
      vitamin D sufficiency and alcohol consumption was evident only in Korean men.

PMID- 22413044
TI  - Interactions between the FTO rs9939609 polymorphism, body mass index, and
      lifestyle-related factors on metabolic syndrome risk.
AB  - Whether the FTO polymorphisms interact with environmental factors has not yet
      been evaluated in associations with metabolic syndrome (MS) risk. The present
      study investigated the association of the FTO rs9939609 genotypes, body mass
      index (BMI), and lifestyle-related factors including smoking, alcohol drinking,
      physical activity, and diet with MS incidence. A population-based prospective
      cohort study comprised 3,504 male and female Koreans aged 40 to 69 years. At the
      beginning of the study, all individuals were free of MS and known cardiovascular
      disease. Incident cases of MS were identified by biennial health examinations
      during a follow-up period from April 17, 2003 to April 15, 2009. Pooled logistic
      regression analysis was applied to obtain relative odds (RO) of MS with its 95%
      confidence interval (CI). After controlling for potential MS risk factors, we
      observed no association between the rs9939609 genotypes and MS incidence. In
      analysis stratified by BMI, however, carriers with the FTO risk allele whose BMI
      is 29 kg/m(2) or greater showed an approximately 6-fold higher RO (95% CI: 3.82
      to 9.30) compared with non-carriers with BMI less than 25 kg/m(2). In particular,
      the association between the rs9939609 variants and MS risk was significantly
      modified by high BMI (P-value for interaction < 0.05). Such significant
      interaction appeared in associations with central obesity and high blood pressure
      among the MS components. Because carriers of the FTO risk alleles who had BMI of
      29 kg/m(2) or greater are considered a high risk population, we suggest that they
      may need intensive weight loss regimens to prevent MS development.

PMID- 22413046
TI  - Circumcision: controversies and prospects.

PMID- 22413047
TI  - Hybrid Frame-based Neuronavigation.

PMID- 22413048
TI  - Surgical management of hemorrhoids.
AB  - Hemorrhoids are common human afflictions known since the dawn of history.
      Surgical management of this condition has made tremendous progress from complex
      ligation and excision procedures in the past to simpler techniques that allow the
      patient to return to normal life within a short period. Newer techniques try to
      improve on the post-operative complications of older ones. The surgical options
      for the management of hemorrhoids today are many. Capturing all in a single
      article may be difficult if not impossible. The aim of this study therefore is to
      present in a concise form some of the common surgical options in current
      literature, highlighting some important post operative complications. Current
      literature is searched using MEDLINE, EMBASE and the Cochrane library. The
      conclusion is that even though there are many surgical options in the management
      of hemorrhoids today, most employ the ligature and excision technique with newer
      ones having reduced post operative pain and bleeding.

PMID- 22413049
TI  - Three-piece Inflatable Penile Prosthesis: Surgical Techniques and Pitfalls.
AB  - Penile prosthesis surgery plays a vital role in the treatment of erectile
      dysfunction (ED). As far as outcome is concerned, it is one of the most rewarding
      procedures for both patients and surgeons. We describe our surgical technique for
      implantation of the three-piece inflatable penile prosthesis and point out the
      major surgical pitfalls accompanying this procedure and their specific
      management. The psychological outcome of penile prosthesis surgery is also
      discussed. Different surgical approaches are available when performing the
      procedure. A number of procedure-related problems can be encountered and a
      thorough knowledge of these is of paramount importance. Penile prosthesis surgery
      has a favorable psychological outcome. Surgery for implantation of an inflatable
      penile prosthesis is a rewarding procedure, with a high yield of patient
      satisfaction. Urologists should have thorough understanding of the surgical
      pitfalls peculiar to this procedure and their management.

PMID- 22413050
TI  - Two-port Laparoscopic-assisted Appendicectomy Under Local Anesthesia in Adults: A
      Pilot Study.
AB  - AIM: Nowadays laparoscopic-assisted appendicectomy using the two-port technique
      is gaining popularity due to its certain benefits over the open version. General
      anesthesia with positive pressure ventilation is the preferred mode of anesthesia
      in this technique. We conducted a pilot study using the two-port technique in
      adult patients, with uncomplicated appendicitis under local anesthesia, to
      evaluate its feasibility. MATERIALS AND METHODS: In this prospective study 12
      consecutive patients of ASA grade I and II, with a mean age of 22.5 years,
      suffering from acute appendicitis, were included. All the patients received
      ondansetron, diazepam, and pentazocine as premedication. Monitored anesthesia
      care was given. The site of trocar insertions were infiltrated with 1% lignocaine
      with adrenalin. The pneumoperitoneum was created using carbon-di-oxide. After
      exteriorization of the appendix using the trocar, appendicectomy was performed as
      in the open procedure. RESULTS: Eleven out of twelve patients were successfully
      operated using this method without converting it into an open method. Two cases
      required an extra port to free the appendix from the adhesion. There were no
      intra- or post-operative complications present. CONCLUSION: Two-port laparoscopic
      assisted appendicectomy under local anesthesia is a safe and effective method for
      uncomplicated appendicitis in adults, and the procedure is suitable where limited
      set-up for anesthesia is present.

PMID- 22413051
TI  - A new system for neuronavigation and stereotactic biopsy pantograph stereotactic
      localization and guidance system.
AB  - Everyday, neurosurgeons face the problem of orientation within the brain but the
      advent of stereotactic surgery and neuronavigation have solved this problem.
      Frame-based stereotactic systems (FBSS) and neuronavigation systems have their
      own strengths and priority and pitfalls, which were the main driving force for us
      to design a new system. This hybrid system comprises three main parts: main
      frame, monitoring system, and pantograph, which are connected to each other and
      to the operating table by particular attachments. For using this system, after
      performing CT SCAN or Magnetic Resonance Imaging (MRI) the axial view will be
      transferred to Liquid Cristal Display (LCD). In the operating room, the head of
      the patient fixes to the operating table and registration is completed by two
      arms of pantograph. We made a simulation operation with our system on an
      occipital cavernous angioma and a frontal oligodendroglioma. The software, which
      have been used for simulation were as follows; Poser (version-7), Catia (version
      5- R18), and 3 Dimension Max (version 2008). The accuracy of this system is
      approximately two millimeter. The advantages of this system are: easy to use,
      much less expensive, and compatible with different devices, which may be needed
      during neurosurgical operation. For countries that do not have the opportunity to
      have sophisticated technology and neuronavigation system, we believe that our
      system is a one-stop solution.

PMID- 22413052
TI  - Capsule endoscopy: new technology, old complication.
AB  - Wireless capsule endoscopy is a new tool in the armamentarium of the
      gastroenterologist to evaluate the small bowel non-invasively. It allows improved
      diagnostic yield with low complication rates relative to traditional modalities.
      But this new technology has its own set of complications, some which can lead to
      significant morbidity. Here, we present a case of complete small bowel
      obstruction following a capsule endoscopy. A 65-year-old female with a long
      standing history of anemia and obscure gastrointestinal bleed presented to the
      Emergency Department 72 hours after a wireless capsule endoscopy procedure
      complaining of worsening abdominal pain, distension, and frequent vomiting. An X
      ray was suggestive of complete distal small bowel obstruction with the capsule at
      the transition point of dilated proximal and collapsed distal small bowel. The
      patient was resuscitated and taken up for an explorative laparotomy where a short
      segment stricture was noted with the capsule endoscope caught proximal to it. The
      segment was resected and patient made an uneventful recovery. Wireless capsule
      endoscopy is now becoming the preferred method to image the small bowel. Our
      report illustrates the importance of appropriate patient selection and evaluation
      of functional patency of the small bowel may be with a contrast series prior to
      wireless capsule endoscopy to avoid any post procedural morbidity.

PMID- 22413053
TI  - Primary cutaneous aspergillosis in an immunocompetent patient.
AB  - We present a 32-year-old woman with primary cutaneous aspergillosis and an
      apparently normal immune status. She is a dietitian who carried out research on
      Aspergillus contamination of palm oil over a six-month period, during which she
      apparently shaved her axillae and perineum using a safety razor blade. She
      presented with nodular lesions, which became extensive ulcers after an attempt at
      incision and drainage. Diagnosis was based on culture and histology. The patient
      was treated with itraconazole 200 mg twice a day, with surgical excision and a
      rhomboid flap cover of the axillae. She has remained disease-free five years
      after discharge. This highlights the likely benefits of a combination of surgical
      excision and drug therapy, in achieving a cure in this patient.

PMID- 22413054
TI  - Encysted hydrocele of canal of nuck: a case report with review of literature.
AB  - The canal of Nuck is analogous to a patent processus vaginalis in a male, which
      normally loses its communication to the peritoneal cavity within the first year
      of life. Failure of obliteration of this tract can result in a hydrocele. We
      present a rare case of a 3-year-old girl with right-sided groin swelling over a
      year, diagnosed as hydrocele of canal of Nuck. Patient underwent surgical
      exploration and excision of hydrocelea. This entity should be considered in young
      females presenting with an inguinal swelling.

PMID- 22413055
TI  - Squamous cell carcinoma arising in a testicular teratoma and presenting as sister
      Mary joseph nodule.
AB  - The most common somatic type malignancy arising in patients with testicular germ
      cell tumors (GCTs) is sarcoma. Development of carcinomas, especially squamous
      cell carcinoma is an extremely rare event. Most cases of metastatic umbilical
      nodules (Sister Mary Joseph nodule) develop from adenocarcinomas. Fifteen percent
      of such cases have unknown origin; but development from a testicular squamous
      cell carcinoma has not yet been reported in the literature. We report a rare case
      of somatic type squamous cell carcinoma arising in a testicular teratoma. It is
      also possibly the first reported case of its kind which presented with a
      metastatic umbilical nodule. This possibility should be kept in mind while
      evaluating metastatic umbilical nodules in young male patients.

PMID- 22413056
TI  - Ankle arthrodesis following trauma, a useful salvage procedure - a report on
      three cases.
AB  - Open musculoskeletal injuries remain a difficult problem to manage especially in
      resource-poor regions. They are complicated by prolonged morbidity and chronic
      osseous infections and sometimes gangrene. Our objective was to look at ankle
      arthrodesis as a primary and useful salvage procedure through simple technique
      for cases of severe open ankle injuries. Three patients with severe open ankle
      injuries between January 2007 and December 2009 were seen and had wound
      debridement done and compressive ankle arthrodesis with a Charnley's arthrodesis
      clamp. Tibiotalar and tibiocalcaneal arthrodesis was the procedure carried out.
      Patients were followed up for 3-12 months. Wound breakdown was seen in two cases
      and one later had skin grafting. All patients expressed satisfaction with the
      outcome of surgery. Ankle arthrodesis is a simple and useful salvage procedure
      for severe ankle disruption, guaranteeing patients satisfaction as against
      amputation.

PMID- 22413057
TI  - Laparoscopic right radical nephrectomy.
AB  - Laparoscopic radical nephrectomy is a minimally invasive surgical procedure and
      is in practice since 1992 in USA. We describe the novel technique of this
      procedure with an added advantage. Controlling renal vessels first at the hilum
      with lymphadenectomy is our principle of surgery. This technique is known as
      transperitoneal medial to lateral approach radical nephrectomy.

PMID- 22413058
TI  - Subarachnoid Hemorrhage in a Three-year-old-boy with Left Middle Cerebral Artery
      Aneurysm.

PMID- 22413059
TI  - On quantum effects in a theory of biological evolution.
AB  - We construct a descriptive toy model that considers quantum effects on biological
      evolution starting from Chaitin's classical framework. There are smart evolution
      scenarios in which a quantum world is as favorable as classical worlds for
      evolution to take place. However, in more natural scenarios, the rate of
      evolution depends on the degree of entanglement present in quantum organisms with
      respect to classical organisms. If the entanglement is maximal, classical
      evolution turns out to be more favorable.

PMID- 22413060
TI  - Specificity quantification of biomolecular recognition and its implication for
      drug discovery.
AB  - Highly efficient and specific biomolecular recognition requires both affinity and
      specificity. Previous quantitative descriptions of biomolecular recognition were
      mostly driven by improving the affinity prediction, but lack of quantification of
      specificity. We developed a novel method SPA (SPecificity and Affinity) based on
      our funneled energy landscape theory. The strategy is to simultaneously optimize
      the quantified specificity of the "native" protein-ligand complex discriminating
      against "non-native" binding modes and the affinity prediction. The benchmark
      testing of SPA shows the best performance against 16 other popular scoring
      functions in industry and academia on both prediction of binding affinity and
      "native" binding pose. For the target COX-2 of nonsteroidal anti-inflammatory
      drugs, SPA successfully discriminates the drugs from the diversity set, and the
      selective drugs from non-selective drugs. The remarkable performance demonstrates
      that SPA has significant potential applications in identifying lead compounds for
      drug discovery.

PMID- 22413061
TI  - Expression of GluK1c underlies the developmental switch in presynaptic kainate
      receptor function.
AB  - Kainate-type glutamate receptors (KARs) regulate synaptic transmission and
      neuronal excitability via multiple mechanisms, depending on their subunit
      composition. Presynaptic KARs tonically depress glutamatergic transmission during
      restricted period of synapse development; however, the molecular basis behind
      this effect is unknown. Here, we show that the developmental and cell-type
      specific expression pattern of a KAR subunit splice variant, GluK1c, corresponds
      to the immature-type KAR activity in the hippocampus. GluK1c localizes to
      dendritic contact sites at distal axons, the distal targeting being promoted by
      heteromerization with the subunit GluK4. Presynaptic expression of GluK1c
      strongly suppresses glutamatergic transmission in cell-pairs in vitro and mimics
      the immature-type KAR activity at CA3-CA1 synapses in vivo, at a developmental
      stage when the endogenous expression is already downregulated. These data support
      a central role for GluK1c in mediating tonic inhibition of glutamate release and
      the consequent effects on excitability and activity-dependent fine-tuning of the
      developing hippocampal circuitry.

PMID- 22413062
TI  - Evidence of associations between feto-maternal vitamin D status, cord parathyroid
      hormone and bone-specific alkaline phosphatase, and newborn whole body bone
      mineral content.
AB  - In spite of a high prevalence of vitamin D inadequacy in pregnant women and
      neonates, relationships among vitamin D status (25(OH)D), parathyroid hormone
      (PTH), bone specific alkaline phosphatase (BALP), and whole body bone mineral
      content (WBBMC) in the newborn are poorly characterized. The purpose of the
      present study was to investigate the relationships between maternal and cord
      25(OH)D, PTH, BALP, and WBBMC in newborns in a multiethnic population in Oakland,
      California and to evaluate the predictive value of the biochemical indices as
      indicators of WBBMC. Maternal and cord blood were collected from 80 mother-infant
      pairs and infant WBBMC was measured by dual energy X-ray absorptiometry 8-21 days
      post-birth. Cord PTH and BALP were each inversely correlated with infant WBBMC (r
      = -0.28, p = 0.01 and r = -0.26, p = 0.02) and with cord 25(OH)D (r = -0.24, p =
      0.03 and r = -0.34, p = 0.002), while cord 25(OH)D and unadjusted or weight
      adjusted WBBMC were not significantly correlated with one other. In multivariate
      regression modeling, infant WBBMC was most strongly predicted by infant weight (p
      < 0.0001), while either PTH or BALP contributed modestly but significantly to the
      model (p = 0.006 and p = 0.03 respectively). Cord 25(OH)D was not a significant
      predictor of infant WBBMC. This study provides evidence of associations between
      feto-maternal 25(OH)D, cord PTH and BALP, and early infant WBBMC, though neither
      feto-maternal 25(OH)D nor the measured biochemical indices were suitable
      indicators of WBBMC.

PMID- 22413063
TI  - Antiapoptotic and antiautophagic effects of eicosapentaenoic acid in cardiac
      myoblasts exposed to palmitic acid.
AB  - Apoptosis is a programmed cell death that plays a critical role in cell
      homeostasis. In particular, apoptosis in cardiomyocytes is involved in several
      cardiovascular diseases including heart failure. Recently autophagy has emerged
      as an important modulator of programmed cell death pathway. Recent evidence
      indicates that saturated fatty acids induce cell death through apoptosis and this
      effect is specific for palmitate. On the other hand, n-3 polyunsaturated fatty
      acids (PUFAs) have been implicated in the protection against cardiovascular
      diseases, cardiac ischemic damage and myocardial dysfunction. In the present
      study we show that n-3 PUFA eicosapentaenoic acid (EPA) treatment to culture
      medium of H9c2 rat cardiomyoblasts protects cells against palmitate-induced
      apoptosis, as well as counteracts palmitate-mediated increase of autophagy.
      Further investigation is required to establish whether the antiautophagic effect
      of EPA may be involved in its cytoprotective outcome and to explore the
      underlying biochemical mechanisms through which palmitate and EPA control the
      fate of cardiac cells.

PMID- 22413064
TI  - Pro- and synbiotics to prevent sepsis in major surgery and severe emergencies.
AB  - Septic morbidity associated with advanced surgical and medical treatments is
      unacceptably high, and so is the incidence of complications occurring in
      connection with acute emergencies such as severe trauma and severe acute
      pancreatitis. Only considering the US, it will annually affect approximately
      (app) 300 million (mill) of a population of almost one million inhabitants and
      cause the death of more than 200,000 patients, making sepsis the tenth most
      common cause of death in the US. Two major factors affect this, the lifestyle
      associated increased weakness of the immune defense systems, but more than this
      the artificial environment associated with modern treatments such as mechanical
      ventilation, use of tubes, drains, intravascular lines, artificial nutrition and
      extensive use of synthetic chemical drugs, methods all known to reduce or
      eliminate the human microbiota and impair immune functions and increase systemic
      inflammation. Attempts to recondition the gut by the supply of microorganisms
      have sometimes shown remarkably good results, but too often failed. Many factors
      contribute to the lack of success: unsuitable choice of probiotic species, too
      low dose, but most importantly, this bio-ecological treatment has never been
      given the opportunity to be tried as an alternative treatment. Instead it has
      most often been applied as complementary to all the other treatments mentioned
      above, including antibiotic treatment. The supplemented lactic acid bacteria have
      most often been killed already before they have reached their targeted organs.

PMID- 22413065
TI  - Assessment of the effect of high or low protein diet on the human urine
      metabolome as measured by NMR.
AB  - The objective of this study was to identify urinary metabolite profiles that
      discriminate between high and low intake of dietary protein during a dietary
      intervention. Seventy-seven overweight, non-diabetic subjects followed an 8-week
      low-calorie diet (LCD) and were then randomly assigned to a high (HP) or low (LP)
      protein diet for 6 months. Twenty-four hours urine samples were collected at
      baseline (prior to the 8-week LCD) and after dietary intervention; at months 1, 3
      and 6, respectively. Metabolite profiling was performed by (1)H NMR and
      chemometrics. Using partial least squares regression (PLS), it was possible to
      develop excellent prediction models for urinary nitrogen (root mean square error
      of cross validation (RMSECV) = 1.63 mmol/L; r = 0.89) and urinary creatinine
      (RMSECV = 0.66 mmol/L; r = 0.98). The obtained high correlations firmly establish
      the validity of the metabolomic approach since urinary nitrogen is a well
      established biomarker for daily protein consumption. The models showed that
      trimethylamine-N-oxide (TMAO) is correlated to urinary nitrogen. Furthermore,
      urinary creatine was found to be increased by the HP diet whereas citric acid was
      increased by the LP diet. Despite large variations in individual dietary intake,
      differentiated metabolite profiles were observed at the dietary group-level.

PMID- 22413066
TI  - Current challenges in detecting food allergens by shotgun and targeted proteomic
      approaches: a case study on traces of peanut allergens in baked cookies.
AB  - There is a need for selective and sensitive methods to detect the presence of
      food allergens at trace levels in highly processed food products. In this work, a
      combination of non-targeted and targeted proteomics approaches are used to
      illustrate the difficulties encountered in the detection of the major peanut
      allergens Ara h 1, Ara h 2 and Ara h 3 from a representative processed food
      matrix. Shotgun proteomics was employed for selection of the proteotypic peptides
      for targeted approaches via selective reaction monitoring. Peanut presence
      through detection of the proteotypic Ara h 3/4 peptides AHVQVVDSNGNR (m/z 432.5,
      3+) and SPDIYNPQAGSLK (m/z 695.4, 2+) was confirmed and the developed method was
      able to detect peanut presence at trace levels (>=10 MUg peanut g(-1) matrix) in
      baked cookies.

PMID- 22413067
TI  - Sense & sensibility.

PMID- 22413068
TI  - Effect of anti-rheumatic agents on periodontal parameters and biomarkers of
      inflammation: a systematic review and meta-analysis.
AB  - PURPOSE: Anti-rheumatic agents target common molecular pathways of inflammation
      in rheumatoid arthritis (RA) and periodontitis. The purpose of this study was to
      determine the relative effect of anti-rheumatic agents on the levels of
      inflammatory biomarkers and periodontal inflammation in RA patients with
      periodontitis. METHODS: A systematic review and meta-analysis were conducted of
      studies comparing periodontal parameters of inflammation, such as bleeding on
      probing, and biomarkers of inflammation in RA patients with periodontitis and
      healthy adults with and without periodontitis. The search included the electronic
      databases MEDLINE, Cochrane Database of Systematic Reviews, and Google Scholar,
      inclusive through October 2011, with no language restrictions. Hand searches were
      conducted of the bibliographies of related journals and systematic reviews.
      Observational and interventional studies assessing the effects of antirheumatic
      therapy qualified for inclusion. Two reviewers performed independent data
      extraction and risk-of-bias assessment. Of the 187 identified publications, 13
      studies fulfilled the inclusion criteria. RESULTS: When compared to healthy
      adults without periodontitis, RA subjects were found to have significantly higher
      levels of bleeding on probing and limited evidence of higher levels of
      interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) in gingival
      crevicular fluid and saliva. No consistent differences were found in periodontal
      parameters and inflammatory biomarkers between RA subjects and adults with
      periodontitis. Studies evaluating the effect of anti-TNF-alpha therapy in RA
      subjects with periodontitis have yielded inconsistent results. CONCLUSIONS: There
      are limited data, however, to suggest that anti-TNF-alpha agents can reduce local
      production of inflammatory cytokines and periodontal inflammation in RA patients
      with periodontitis.

PMID- 22413069
TI  - In situ dental implant installation after decontamination in a previously peri
      implant diseased site: a pilot study.
AB  - PURPOSE: The aim of this study was to examine whether a previous peri-implantitis
      site can affect osseointegration, by comparing implant placement at a site where
      peri-implantitis was present and at a normal bone site. A second aim of this
      study was to identify the tissue and bone reaction after treating the
      contaminated implant surface to determine the optimal treatment for peri-implant
      diseases. METHODS: A peri-implant mucositis model for dogs was prepared to
      determine the optimal treatment option for peri-implant mucositis or peri
      implantitis. The implants were inserted partially to a length of 6 mm. The upper
      4 mm part of the dental implants was exposed to the oral environment. Simple
      exposure for 2 weeks contaminated the implant surface. After 2 weeks, the
      implants were divided into three groups: untreated, swabbed with saline, and
      swabbed with H(2)O(2). Three implants from each group were placed to the full
      length in the same spot. The other three implants were placed fully into newly
      prepared bone. After eight weeks of healing, the animals were sacrificed. Ground
      sections, representing the mid-buccal-lingual plane, were prepared for
      histological analysis. The analysis was evaluated clinically and histometrically.
      RESULTS: The untreated implants and H(2)O(2)-swabbed implants showed gingival
      inflammation. Only the saline-swabbed implant group showed re-osseointegration
      and no gingival inflammation. There was no difference in regeneration height or
      bone-to-implant contact between in situ implant placement and implant placement
      in the new bone site. CONCLUSIONS: It can be concluded that cleaning with saline
      may be effective in implant decontamination. After implant surface
      decontamination, implant installation in a previous peri-implant diseased site
      may not interfere with osseointegration.

PMID- 22413070
TI  - The effect of peri-implant bone exposure on soft tissue healing and bone loss in
      two adjacent implants.
AB  - PURPOSE: The purpose of this study was to evaluate the soft tissue and bone
      change around two adjacent implants in one-stage implant surgery. METHODS: Eleven
      subjects (7 males, 4 females) who were needed placement of 2 adjacent implants in
      the molar area were included. The two implants were placed with the platform at
      the level of the alveolar crest. The interproximal bone between the 2 implants
      was not covered with gingiva. After surgery, an alginate impression was taken to
      record the gingival shape and radiographs were taken to evaluate implant
      placement. Using a master cast, the gingival height was measured at baseline, 4
      weeks, and 12 weeks. In the radiograph, the alveolar bone level was measured at
      the mesial and distal side of both implants at baseline and 12 weeks. RESULTS:
      The exposed bone was covered with gingiva at both 4 and 12 weeks. Loss of
      alveolar bone around implants was found in all areas. The alveolar bone level in
      the exposed bone area did not differ from that in the non-exposed area.
      CONCLUSIONS: This study showed that the alveolar bone level and gingival height
      around 2 adjacent implants in the exposed bone area did not differ from that in
      unexposed bone area.

PMID- 22413071
TI  - Development of the implant surgical technique and assessment rating system.
AB  - PURPOSE: There has been no attempt to establish an objective implant surgical
      evaluation protocol to assess residents' surgical competence and improve their
      surgical outcomes. The present study presents a newly developed assessment and
      rating system and simulation model that can assist the teaching staffs to
      evaluate the surgical events and surgical skills of residents objectively.
      METHODS: Articles published in peer-reviewed English journals were selected using
      several scientific databases and subsequently reviewed regarding surgical
      competence and assessment tools. Particularly, medical journals reporting rating
      and evaluation protocols for various types of medical surgeries were thoroughly
      analyzed. Based on these studies, an implant surgical technique assessment and
      rating system (iSTAR) has been developed. Also, a specialized dental typodont was
      developed for the valid and reliable assessment of surgery. RESULTS: The iSTAR
      consists of two parts including surgical information and task-specific
      checklists. Specialized simulation model was subsequently produced and can be
      used in combination with iSTAR. CONCLUSIONS: The assessment and rating system
      provided may serve as a reference guide for teaching staffs to evaluate the
      residents' implant surgical techniques.

PMID- 22413072
TI  - Robotic colorectal surgery: is it still on the way to a landmark?

PMID- 22413073
TI  - Will the Stroma-derived Factor-1alpha (CXCL12)/CXCR4 Pathway Become a Major
      Concern for Advanced Colorectal Cancer?

PMID- 22413074
TI  - Laparoscopic right hemicolectomy for colon cancer: technically feasible and safe
      to perform in terms of oncologic outcomes.

PMID- 22413075
TI  - Early detection of colorectal cancer, is it a guarantee for the cure of cancer?

PMID- 22413076
TI  - New techniques for treating an anal fistula.
AB  - Surgery for an anal fistula may result in recurrence or impairment of continence.
      The ideal treatment for an anal fistula should be associated with low recurrence
      rates, minimal incontinence and good quality of life. Because of the risk of a
      change in continence with conventional techniques, sphincter-preserving
      techniques for the management complex anal fistulae have been evaluated. First,
      the anal fistula plug is made of lyophilized porcine intestinal submucosa. The
      anal fistula plug is expected to provide a collagen scaffold to promote tissue in
      growth and fistula healing. Another addition to the sphincter-preserving options
      is the ligation of intersphincteric fistula tract procedure. This technique is
      based on the concept of secure closure of the internal opening and concomitant
      removal of infected cryptoglandular tissue in the intersphincteric plane.
      Recently, cell therapy for an anal fistula has been described. Adipose-derived
      stem cells have two biologic properties, namely, ability to suppress inflammation
      and differentiation potential. These properties are useful for the regeneration
      or the repair of damaged tissues. This article discusses the rationales for, the
      estimated efficacies of, and the limitations of new sphincter-preserving
      techniques for the treatment of anal fistulae.

PMID- 22413077
TI  - Delorme's Procedure for Complete Rectal Prolapse: Does It Still Have It's Own
      Role?
AB  - PURPOSE: Although there are more than a hundred techniques, including the
      transabdominal and the perineal approaches, for the repair of the rectal
      prolapsed, none of them is perfect. The best repair should be chosen not only to
      correct the prolapse but also to restore defecatory function and to improve fecal
      incontinence throughout the patient's lifetime. The aim of this retrospective
      review is to evaluate clinical outcomes of the Delorme's procedure for the
      management of the complete rectal prolapse. METHODS: A total of 19 patients (13
      females and 6 males) with complete rectal prolapses were treated by using the
      Delorme's procedure in St. Vincent's Hospital, The Catholic University of Korea,
      from February 1997 to February 2007. Postoperative anal incontinence was
      evaluated using the Cleveland Clinic Incontinence Score. RESULTS: All 19 patients
      had incontinence to liquid stool, solid stool, and/or flatus preoperatively.
      Three (15.8%) patients reported recurrence of the rectal prolapse (at 6, 18, 29
      months, respectively, after the operation). Information on postoperative
      incontinence was available for 16 of the 19 patients. Twelve of the 16 patients
      (75%) reported improved continence (5 [31.3%] were improved and 7 [43.7%]
      completely recovered from incontinence) while 4 patients had unchanged
      incontinence symptoms. One (6.3%) patient who did not have constipation
      preoperatively developed constipation after the operation. CONCLUSION: The
      Delorme's procedure is associated with a marked improvement in anal continence,
      relatively low recurrence rates, and low incidence of postoperative constipation.
      This allows us to conclude that this procedure still has its own role in selected
      patients.

PMID- 22413078
TI  - Comparison of Short-term Surgical Outcomes between a Robotic Colectomy and a
      Laparoscopic Colectomy during Early Experience.
AB  - PURPOSE: Although robotic surgery was invented to overcome the technical
      limitations of laparoscopic surgery, the role of a robotic (procto)colectomy (RC)
      for the treatment of colorectal cancer compared to that of a laparoscopic
      (procto)colectomy (LC) was not well defined during the initial adoption periods
      of both procedures. This study aimed to evaluate the efficacy and the safety of a
      RC for the treatment of colorectal cancer by comparing the authors' initial
      experiences with both a RC and a LC. METHODS: The first 30 patients treated by
      using a RC for colorectal cancer from July 2010 to March 2011 were compared with
      the first 30 patients treated by using a LC for colorectal cancer from December
      2006 to June 2007 by the same surgeon. Perioperative variables and short-term
      outcomes were analyzed. In addition, the 30 RC and the 30 LC cases involved were
      divided into rectal cancer (n = 17 and n = 12, respectively), left-sided colon
      cancer (n = 7 and n = 12, respectively) and right-sided colon cancer (n = 6 and n
      = 6, respectively) for subgroup analyses. RESULTS: The mean operating times for
      RC and LC were significantly different at 371.8 and 275.5 minutes, respectively,
      but other perioperative parameters (rates of open conversion, numbers of
      retrieved lymph node, estimated blood losses, times to first flatus, maximal pain
      scores before discharge and postoperative hospital stays) were not significantly
      different in the two groups. Subgroup analyses showed that the mean operative
      times for a robotic proctectomy and a laparoscopic proctectomy were 396.5 and
      298.8 minutes, respectively (P < 0.000). Postoperative complications occurred in
      five patients in the RC group and in six patients in the LC group (P = 0.739).
      CONCLUSION: Although the short-term outcomes of a RC during its initial use were
      better than those of a LC (with the exception of operating time), differences
      were not found to be significantly different. On the other hand, the longer
      operation time of a robotic proctectomy compared to that of a laparoscopic
      proctectomy during the early period may be problematic.

PMID- 22413079
TI  - Stromal-cell-derived Factor 1-alpha Promotes Tumor Progression in Colorectal
      Cancer.
AB  - PURPOSE: Although stromal-cell-derived factor (SDF)-1alpha is suggested to be
      involved in tumorigenicity and tumor angiogenesis, the clinicopathological
      significance of its expression in colorectal cancers is not fully understood. We
      examined SDF-1alpha expression in colorectal cancers and investigated its
      relationship to clinicopathological features such as tumor staging, lymph-node
      metastasis, vascular invasion (VI), lymphatic invasion (LI) and neural invasion
      (NI). METHODS: Specimens of 83 primary colorectal cancers were examined
      immunohistochemically, and the relationships between clinicopathological features
      and SDF-1alpha expression were analyzed. To compare the expressions between the
      normal colon tissue and colorectal cancer tissues, we performed Western blot
      analyses. RESULTS: According to the Western blot analyses, SDF-1alpha was more
      highly expressed in colorectal carcinoma tissues than in normal colonic mucosa
      (20/21). According to the immunohistochemical stain, SDF-1alpha was associated
      with nodal status, distant metastasis, tumor staging, VI and LI. SDF-1alpha
      expression had a significant prognostic value for overall survival. Kaplan-Meier
      plots of survival in patients with high SDF-1alpha showed that high SDF-1alpha
      expression was associated with a shorter overall survival. However, no
      association was found between SDF-1alpha expression and other pathologic or
      clinical variables, including age, gender, degree of differentiation, and
      presence of perineural invasion. CONCLUSION: The expression of SDF-1alpha might
      be associated with tumor progression in colorectal cancer. Inhibition of SDF
      1alpha could be a therapeutic option in colorectal cancer patients.

PMID- 22413080
TI  - Multivariate Analysis of the Survival Rate for Treatment Modalities in Incurable
      Stage IV Colorectal Cancer.
AB  - PURPOSE: The aim of this study was to compare survival in patients that underwent
      palliative resection treatment versus non-resection for incurable colorectal
      cancer (ICRC). METHODS: The case records of 201 patients with ICRC between
      January 2000 and December 2009 were reviewed. Demographics, American Society of
      Anesthesiologists (ASA) score, carcinoembryonic antigen (CEA) level, the location
      of the colon cancer, histology, metastasis, treatment options and median survival
      were analyzed retrospectively. We divided the patients into four groups according
      to the treatment modalities: resection alone, resection with post-operative
      chemotherapy, non-resection treatment by chemotherapy alone, and stent or bypass.
      Median survival times were compared according to each treatment option, and the
      survival rates were analyzed. RESULTS: 105 patients underwent palliative
      resection whereas 96 were treated with non-resection modalities. A palliative
      resection was performed in 44 cases for resection alone and in 61 cases for
      resection with post-operative chemotherapy. In patients treated with non
      resection of the primary tumor, chemotherapy alone was done in 65 cases and stent
      or bypass in 31 cases. Multivariate analysis showed a median survival of 14
      months in patients with palliative resections with post-operative chemotherapy,
      which was significantly higher than those for chemotherapy alone (8 months),
      primary tumor resection alone (5 months), and stent or bypass (5 months). Gender,
      age, ASA score, CEA level, the location of colon cancer, histology and the
      presence of multiple metastases were not independent factors in association with
      the median survival rate. CONCLUSION: In the treatment of ICRC, palliative
      resection followed by post-operative chemotherapy shows the most favorable median
      survival compared to other treatment options.

PMID- 22413081
TI  - Oncologic Outcomes of a Laparoscopic Right Hemicolectomy for Colon Cancer:
      Results of a 3-Year Follow-up.
AB  - PURPOSE: The purpose of the study is to evaluate the oncologic outcomes of a
      laparoscopic-assisted right hemicolectomy for the treatment of colon cancer and
      compare the results with those of previous randomized trials. METHODS: From June
      2006, to December 2008, 156 consecutive patients who underwent a laparoscopic
      right hemicolectomy with a curative intent for colon cancer were evaluated. The
      clinicopatholgic outcomes and the oncologic outcomes were evaluated
      retrospectively by using electronic medical records. RESULTS: There were 84 male
      patients and 72 female patients. The mean possible length of stay was 7.0 +/- 1.5
      days (range, 4 to 12 days). The conversion rate was 3.2%. The total number of
      complications was 30 (19.2%). Anastomotic leakage was not noted. There was no
      mortality within 30 days. The 3-year overall survival rate of all stages was
      93.3%. The 3-year overall survival rates according to stages were 100% in stage
      I, 97.3% in stage II, and 84.8% in stage III. The 3-year disease-free survival
      rate of all stages was 86.1%. The 3-year disease-free survival rates according to
      stage were 96.2% in stage I, 90.3% in stage II, and 75.6% in stage III. The mean
      follow-up period was 36.3 (3 to 60) months. CONCLUSION: A laparoscopic right
      hemicolectomy for the treatment of colon cancer is technically feasible and safe
      to perform in terms of oncologic outcomes. The present data support previously
      reported randomized trials.

PMID- 22413082
TI  - Clinicopathologic factors affecting recurrence after curative surgery for stage I
      colorectal cancer.
AB  - PURPOSE: The objective of the current study was to identify the
      clinicopathological risk factors affecting recurrence after a curative resection
      for stage I colorectal cancer. METHODS: We retrospectively studied 434 patients
      who underwent a curative resection for stage I colorectal cancer between January
      1999 and December 2004. Postoperative oral chemotherapy was performed in 189
      patients (45.3%). The following prognostic factors were correlated with
      recurrence: age, gender, preoperative carcinoembryonic antigen level, location of
      tumor, T stage, size of tumor, histologic differentiation, growth pattern, and
      lymphovascular invasion. The median follow-up duration was 65 months. RESULTS:
      The overall recurrence rate was 4.6% (20/434). The median time to recurrence was
      33 months. Two-thirds of the recurrence occurred more than two years after
      surgery. Risk factors associated with recurrence were rectal cancer (P = 0.009),
      T2 stage (P = 0.010), and infiltrative growth pattern (P = 0.020). A Cox
      proportional hazards regression analysis demonstrated that the infiltrative
      growth pattern was an independent predictor for recurrence. Tumor cell budding
      was observed in all pathologic reviews with recurrence. CONCLUSION: Long-term
      follow-up is necessary for stage I colorectal patients with high risk factors
      like rectal cancer, T2 stage, and infiltrative growth pattern.

PMID- 22413083
TI  - Operative treatment with a laparotomy for anorectal problems arising from a self
      inserted foreign body.
AB  - An anorectal foreign body can cause serious complications such as incontinence,
      rectal perforation, peritonitis, or pelvic abscess, so it should be managed
      immediately. We experienced two cases of operative treatment for a self-inserted
      anorectal foreign body. In one, the foreign body could not be removed as it was
      completely impacted in the anal canal. We failed to remove it through the anus. A
      laparotomy and removal of the foreign body was performed by using an incision on
      the rectum. Primary colsure and a sigmoid loop colostomy were done. A colostomy
      take-down was done after three months. The other was a rectal perforation from
      anal masturbation with a plastic device. We performed primary repair of the
      perforated rectosigmoid colon, and we didea sigmoid loop colostom. A colostomy
      take-down was done three months later. Immediate and proper treatment for a self
      inserted anorectal foreign body is important to prevent severe complications, and
      we report successful surgical treatments for problems caused by anorectal foreign
      bodies.

PMID- 22413084
TI  - Extensive bowel ischemia with heavy alcohol consumption: report of a case.
AB  - Alcohol is well-recognized systemic toxin that causes numerous adverse effects,
      including psychosocial problems, fatal myocardial infarction, stroke and
      atherosclerosis. The intra-abdominal complications caused by acute alcohol
      consumption have not been defined. We report an 80-year-old man with sub-acute
      small bowel and colonic ischemia after heavy alcohol intake in one sitting. We
      performed a resection of gangrenous bowel segments. Microscopically, there were
      diffuse infarction, with vasoconstriction of the mesenteric vessels in the ileum
      and colon without any thrombotic occlusion of the intestinal vessels. The
      clinicians should always be assured by confirmation of a history of recent
      substance abuse in patients with unexplained abdominal pain, and mesenteric
      ischemia should be considered in the differential diagnosis of acute or chronic
      abdominal pain in consumers of alcohol.

PMID- 22413085
TI  - Integration of the Draft Sequence and Physical Map as a Framework for Genomic
      Research in Soybean (Glycine max (L.) Merr.) and Wild Soybean (Glycine soja Sieb.
      and Zucc.).
AB  - Soybean is a model for the legume research community because of its importance as
      a crop, densely populated genetic maps, and the availability of a genome
      sequence. Even though a whole-genome shotgun sequence and bacterial artificial
      chromosome (BAC) libraries are available, a high-resolution, chromosome-based
      physical map linked to the sequence assemblies is still needed for whole-genome
      alignments and to facilitate map-based gene cloning. Three independent G. max BAC
      libraries combined with genetic and gene-based markers were used to construct a
      minimum tiling path (MTP) of BAC clones. A total of 107,214 clones were assembled
      into 1355 FPC (FingerPrinted Contigs) contigs, incorporating 4628 markers and
      aligned to the G. max reference genome sequence using BAC end-sequence
      information. Four different MTPs were made for G. max that covered from 92.6% to
      95.0% of the soybean draft genome sequence (gmax1.01). Because our purpose was to
      pick the most reliable and complete MTP, and not the MTP with the minimal number
      of clones, the FPC map and draft sequence were integrated and clones with
      unpaired BES were added to build a high-quality physical map with the fewest gaps
      possible (http://soybase.org). A physical map was also constructed for the
      undomesticated ancestor (G. soja) of soybean to explore genome variation between
      G. max and G. soja. 66,028 G. soja clones were assembled into 1053 FPC contigs
      covering approximately 547 Mbp of the G. max genome sequence. These physical maps
      for G. max and its undomesticated ancestor, G. soja, will serve as a framework
      for ordering sequence fragments, comparative genomics, cloning genes, and
      evolutionary analyses of legume genomes.

PMID- 22413086
TI  - Homology-dependent silencing by an exogenous sequence in the Drosophila germline.
AB  - The study of P transposable element repression in Drosophila melanogaster led to
      the discovery of the trans-silencing effect (TSE), a homology-dependent
      repression mechanism by which a P-transgene inserted in subtelomeric
      heterochromatin (Telomeric Associated Sequences) represses in trans, in the
      female germline, a homologous P-lacZ transgene inserted in euchromatin. TSE shows
      variegation in ovaries and displays a maternal effect as well as epigenetic
      transmission through meiosis. In addition, TSE is highly sensitive to mutations
      affecting heterochromatin components (including HP1) and the Piwi-interacting RNA
      silencing pathway (piRNA), a homology-dependent silencing mechanism that
      functions in the germline. TSE appears thus to involve the piRNA-based silencing
      proposed to play a major role in P repression. Under this hypothesis, TSE may
      also be established when homology between the telomeric and target loci involves
      sequences other than P elements, including sequences exogenous to the D.
      melanogaster genome. We have tested whether TSE can be induced via lacZ sequence
      homology. We generated a piggyBac-otu-lacZ transgene in which lacZ is under the
      control of the germline ovarian tumor promoter, resulting in strong expression in
      nurse cells and the oocyte. We show that all piggyBac-otu-lacZ transgene
      insertions are strongly repressed by maternally inherited telomeric P-lacZ
      transgenes. This repression shows variegation between egg chambers when it is
      incomplete and presents a maternal effect, two of the signatures of TSE. Finally,
      this repression is sensitive to mutations affecting aubergine, a key player of
      the piRNA pathway. These data show that TSE can occur when silencer and target
      loci share solely a sequence exogenous to the D. melanogaster genome. This
      functionally supports the hypothesis that TSE represents a general repression
      mechanism which can be co-opted by new transposable elements to regulate their
      activity after a transfer to the D. melanogaster genome.

PMID- 22413087
TI  - Ancestry informative marker set for han chinese population.
AB  - The population of Han Chinese is ~1.226 billion people. Genetic heterogeneity
      between northern Han Chinese (N-Han) and southern Han Chinese (S-Han) has been
      demonstrated by recent genome-wide studies. As an initial step toward health
      disparities and personalized medicine in Chinese population, this study developed
      a set of ancestry informative markers (AIM) for Han Chinese population.

PMID- 22413088
TI  - Loss-of-Function Screen Reveals Novel Regulators Required for Drosophila Germline
      Stem Cell Self-Renewal.
AB  - The germline stem cells (GSCs) of Drosophila melanogaster ovary provide an
      excellent model system to study the molecular mechanisms of stem cell self
      renewal. To reveal novel factors required for Drosophila female GSC maintenance
      and/or division, we performed a loss-of-function screen in GSCs by using a
      collection of P-element-induced alleles of essential genes. Mutations in genes of
      various functional groups were identified to cause defects in GSC self-renewal.
      Here we report that a group of mutations affecting various ubiquitin-conjugating
      enzymes cause significant GSCs loss, including Plenty of SH3s (POSH), Ubiquitin
      conjugating enzyme 10 (UbcD10), and pineapple eye (pie). Ubiquitin-mediated
      protein degradation plays a variety of roles in the regulation of many
      developmental processes, including mediating stem cell division through
      degradation of cell cycle regulators. We demonstrated that pie, sharing highly
      conserved RING domains with human E3 ubiquitin ligase G2E3 that are critical for
      early embryonic development, is specifically required for GSC maintenance,
      possibly through regulation of bone morphogenetic protein signaling pathway.
      Despite the previously reported role in imaginal disc cell survival, pie loss-of
      function induced GSC loss is not to the result of caspase-involved cell death.
      Further efforts are needed to elucidate the functions of ubiquitin ligases in GSC
      maintenance, which will ultimately contribute to a better understanding of how
      the ubiquitin-conjugating enzymes regulate stem cell biology in mammalian
      systems.

PMID- 22413089
TI  - Production of a natural antibody to the mouse polyoma virus is a multigenic
      trait.
AB  - MA/MyJ mice express a natural antibody to the highly oncogenic polyoma virus.
      C57BR/cdJ mice lack this antibody but mount an adaptive T-cell response to the
      virus. Analysis of F2 progeny of a cross between these strains reveals a pattern
      of inheritance of expression of the natural antibody involving two genes in an
      epistatic relationship.

PMID- 22413090
TI  - A high-density simple sequence repeat-based genetic linkage map of switchgrass.
AB  - Switchgrass (Panicum virgatum) has been identified as a promising cellulosic
      biofuel crop in the United States. Construction of a genetic linkage map is
      fundamental for switchgrass molecular breeding and the elucidation of its genetic
      mechanisms for economically important traits. In this study, a novel population
      consisting of 139 selfed progeny of a northern lowland genotype, NL 94 LYE 16X13,
      was used to construct a linkage map. A total of 2493 simple sequence repeat
      markers were screened for polymorphism. Of 506 polymorphic loci, 80.8% showed a
      goodness-of-fit of 1:2:1 segregation ratio. Among 469 linked loci on the
      framework map, 241 coupling vs. 228 repulsion phase linkages were detected that
      conformed to a 1:1 ratio, confirming disomic inheritance. A total of 499 loci
      were mapped to 18 linkage groups (LG), of which the cumulative length was 2085.2
      cM, with an average marker interval of 4.2 cM. Nine homeologous LG pairs were
      identified based on multi-allele markers and comparative genomic analysis. Two
      clusters of segregation-distorted loci were identified on LG 5b and 9b,
      respectively. Comparative analysis indicated a one-to-one relationship between
      nine switchgrass homeologous groups and nine foxtail millet (Setaria italica)
      chromosomes, suggesting strong homology between the two species. The linkage map
      derived from selfing a heterozygous parent, instead of two separate maps usually
      constructed for a cross-fertilized species, provides a new genetic framework to
      facilitate genomics research, quantitative trait locus (QTL) mapping, and marker
      assisted breeding.

PMID- 22413091
TI  - A screen for round egg mutants in Drosophila identifies tricornered, furry, and
      misshapen as regulators of egg chamber elongation.
AB  - The elongation of tissues and organs during embryonic development results from
      the coordinate polarization of cell behaviors with respect to the elongation
      axis. Within the Drosophila melanogaster ovary, initially spherical egg chambers
      lengthen dramatically as they develop to create the elliptical shape of the
      mature egg. This morphogenesis depends on an unusual form of planar polarity
      within the egg chamber's outer epithelial cell layer known as the follicle cells.
      Disruption of follicle cell planar polarity leads to the production of round
      rather than elongated eggs; however, the molecular mechanisms that control this
      tissue organization are poorly understood. Starting from a broadly based forward
      genetic screen, we have isolated 12 new round egg complementation groups, and
      have identified four of the mutated genes. In mapping the largest complementation
      group to the fat2 locus, we unexpectedly discovered a high incidence of cryptic
      fat2 mutations in the backgrounds of publicly available stocks. Three other
      complementation groups correspond to the genes encoding the cytoplasmic signaling
      proteins Tricornered (Trc), Furry (Fry), and Misshapen (Msn). Trc and Fry are
      known members of an NDR kinase signaling pathway, and as a Ste20-like kinase, Msn
      may function upstream of Trc. We show that all three proteins are required for
      follicle cell planar polarity at early stages of egg chamber elongation and that
      Trc shows a planar polarized distribution at the basal follicle cell surface.
      These results indicate that this new mutant collection is likely to provide novel
      insight into the molecular mechanisms controlling follicle cell planar polarity
      and egg chamber elongation.

PMID- 22413092
TI  - Coding Gene Single Nucleotide Polymorphism Mapping and Quantitative Trait Loci
      Detection for Physiological Reproductive Traits in Brook Charr, Salvelinus
      fontinalis.
AB  - A linkage map of 40 linkage groups (LGs) was developed for brook charr,
      Salvelinus fontinalis, using an F(2) interstrain hybrid progeny (n = 171) and 256
      coding gene SNP developed specifically for brook charr and validated from a large
      (>1000) subset of putative SNP, as well as 81 microsatellite markers. To identify
      quantitative trait loci (QTL) related to reproduction functions, these fish were
      also phenotyped at six physiological traits, including spermatozoid head
      diameter, sperm concentration, plasma testosterone, plasma 11-keto-testosterone,
      egg diameter, and plasma 17beta-estradiol. Five significant QTL were detected
      over four LGs for egg diameter and plasma 17beta-estradiol concentration in
      females, and sperm concentration as well as spermatozoid head diameter in males.
      In females, two different QTLs located on LG 11 and LG 34 were associated with
      the egg number, whereas one QTL was associated with plasma 17beta-estradiol
      concentration (LG 8). Their total percent variance explained (PVE) was 26.7% and
      27.6%, respectively. In males, two QTL were also detected for the sperm
      concentration, and their PVE were estimated at 18.58% and 14.95%, respectively.
      The low QTL number, associated with the high PVE, suggests that the variance in
      these reproductive physiological traits was either under the control of one major
      gene or a small number of genes. The QTL associated with sperm concentration,
      plasma 17beta-estradiol, and egg diameter appeared to be under a dominance
      effect, whereas the two others were under a negative additive effect. These
      results show that genes underlying the phenotypic variance of these traits are
      under different modes of action (additive vs. dominance) and may be used to
      predict an increase or a decrease in their phenotypic values in subsequent
      generations of selective breeding. Moreover, this newly developed panel of mapped
      SNP located in coding gene regions will be useful for screening wild populations,
      especially in the context of investigating the genetic impact of massive stocking
      of domestic brook charr to support the angling industry throughout eastern North
      America.

PMID- 22413093
TI  - Genetic screen for regulators of lymph gland homeostasis and hemocyte maturation
      in Drosophila.
AB  - Blood cell development in the Drosophila lymph gland is controlled by multiple
      factors, most of them conserved from flies to mammals. The Drosophila homolog of
      vertebrate PDCD2, Zfrp8, is required in Drosophila hematopoietic stem cell
      development. Zfrp8 mutant larvae show a disruption of homeostasis in the lymph
      gland and vast lymph gland overgrowth. The loss of one copy of Zfrp8 also causes
      a lymph gland enlargement. This dominant phenotype can be modified by
      heterozygous mutations in cell-cycle genes and several genes functioning in blood
      development. To identify additional genes that function in hematopoiesis, we
      screened a collection of second and third chromosome deficiencies for modifiers
      of Zfrp8 heterozygous phenotype. Using deficiency mapping, available single gene
      mutations, and RNAi lines, we identified several novel factors required for lymph
      gland development and hemocyte differentiation. Distinct lymph gland phenotypes
      of nine of these genes are reported here for the first time. Importantly, the
      orthologs of four of them have a role in mammalian blood development and
      leukemogenesis. Our work has shown that the number of genes regulating normal
      blood cell development in Drosophila is much larger than expected, and that the
      complex molecular mechanisms regulating hemocyte differentiation are comparable
      to those in vertebrates.

PMID- 22413094
TI  - Haplotype Analysis and Linkage Disequilibrium at Five Loci in Eragrostis tef.
AB  - Eragrostis tef (Zucc.), a member of the Chloridoideae subfamily of grasses, is
      one of the most important food crops in Ethiopia. Lodging is the most important
      production problem in tef. The rht1 and sd1 dwarfing genes have been useful for
      improving lodging resistance in wheat and rice, respectively, in what has been
      known as the "Green Revolution." All homologs of rht1 and sd1 were cloned and
      sequenced from 31 tef accessions collected from across Ethiopia. The
      allotetraploid tef genome was found to carry two rht1 homologs. From sequence
      variation between these two putative homologs, an approximate ancestral
      divergence date of 6.4 million years ago was calculated for the two genomes
      within tef. Three sd1 homologs were identified in tef, with unknown
      orthologous/paralogous relationships. The genetic diversity in the 31 studied
      accessions was organized into a relatively small number of haplotypes (2-4) for
      four of these genes, whereas one rht1 homeologue exhibited 10 haplotypes. A low
      level of nucleotide diversity was observed at all loci. Linkage disequilibrium
      analysis demonstrated strong linkage disequilibrium, extending the length of the
      five genes investigated (2-4 kb), with no significant decline. There was no
      significant correlation between haplotypes of any of these genes and their
      recorded site of origin.

PMID- 22413098
TI  - Incidence of dog bite injuries in American Samoa and their impact on society.
AB  - INTRODUCTION: In American Samoa, a US Territory in the South Pacific, over half
      of reported injuries are attributed to dog bites. Despite years of public outcry,
      little has been done to adequately address these preventable injuries that affect
      all age groups of both sexes. OBJECTIVE: To describe a serious public health
      hazard in American Samoa that may plague other jurisdictions that tolerate a
      significant free-roaming dog population. METHODS: A limited data set of
      outpatient records from 2004 through 2010 from the Territory's only emergency
      department listing an ICD-9-CM E-code of E906.0 ("dog bite") in the primary E
      code field provided a record of dog bite injuries. A survey of 437 adolescents
      documented their experiences regarding unprovoked dog attacks during the
      2010/2011 school year. RESULTS: The sex/age group with the highest incidence for
      dog bite treatment was males 55 to 59 years of age (73.1 per 10,000 population
      per year) followed closely by males 10 to 14 years of age (71.8 per 10,000
      population per year). Males aged 5 to 14 years accounted for 23% of all emergency
      department visits for dog bites. About one-third of adolescents reported having
      been bitten by a dog between September 2010 and May 2011. About 10% of males and
      16% of females attributed the fear of being bitten as a factor preventing them
      from getting more physical activity. CONCLUSIONS: Children, adolescents, and the
      elderly are the most vulnerable to dog bite injuries. Emergency room records may
      reflect only about a quarter of all such injuries. IMPLICATIONS: Unprovoked
      attacks by aggressive, free-roaming dogs degrade quality of life by placing an
      untenable burden on the health care system and imposing physical and
      psychological barriers toward a more healthful lifestyle that includes walking,
      jogging, and bicycling.

PMID- 22413099
TI  - Autoimmune pancreatitis in an Asian-dominant American population.
AB  - Autoimmune pancreatitis is a rare type of chronic pancreatitis that occurs
      predominantly in males and was first described in the Asian population. The
      following study seeks to characterize autoimmune pancreatitis in Hawai'i's Asian
      dominant population through a retrospective review of 65 pancreaticoduodenectomy
      cases performed between 2000 and 2010. Three of the 65 pancreaticoduodenectomies
      were diagnosed with autoimmune pancreatitis, and 3 additional cases were
      diagnosed prior to surgery. All six patients were males and presented with
      obstructive jaundice, 5 with weight loss, and 4 with epigastric pain and elevated
      serum lipase. All six patients showed elevated serum IgG4. Imaging revealed
      findings typical of pancreatic malignancy: distal bile duct stricture and
      pancreatic head mass. However, no nodal involvement and vascular invasion were
      found. In conclusion, autoimmune pancreatitis should be considered in patients
      presenting with obstructive jaundice. Elevated serum IgG4, normal serum
      carbohydrate antigen CA19-9, a benign fine needle aspiration/core biopsy, and a
      therapeutic response to corticosteroid are typical findings of autoimmune
      pancreatitis. Serum IgG4 measurement is a useful tool to help differentiate
      autoimmune pancreatitis from most pancreatic cancers. It is important to consider
      autoimmune pancreatitis as a differential diagnosis of pancreatic malignancy to
      avoid unnecessary surgery.

PMID- 22413100
TI  - Short same-segment fixation of thoracolumbar burst fractures.
AB  - INTRODUCTION: Minimizing the number of vertebral levels involved in fusion of a
      spine fracture is a common goal of internal fixation. This is achievable by
      utilizing traditional short-segment posterior fixation (SSPF). However, in SSPF
      there is reported up to a 54% incidence of instrument failure or unfavorable
      clinical outcome. Short-segment posterior fixation with pedicle fixation at the
      level of the fracture (short same-segment fixation) suggests biomechanical
      advantages toward maintenance of kyphosis correction and reducing failure rates.
      However its clinical efficacy is largely unknown. METHODS: The team conducted a
      retrospective review of 25 thoracolumbar burst fracture patients who were treated
      with short same-segment fixation between September 2005 and April 2009. The
      primary outcome measure was incidence of reoperation and loss of kyphosis
      correction within the follow-up period. Long-term functional status and pain was
      also assessed. RESULTS: Average duration of the most recent follow-up was 21.64
      months (range 3 to 42 months). Two patients (8%) required reoperation due to
      either hardware failure or pseudoarthrosis. Mean pre-operative kyphosis was 14.49
      degrees . Average post-operative kyphosis was -0.74 degrees  (lordosis). Average
      follow-up kyphosis of all cases was 10.78 degrees . Excluding failures, average
      follow-up kyphosis was 8.67 degrees . A mean of 15.23 degrees  of kyphosis
      correction was attained from pre-operation to post-operation (P < 0.0001).
      Average loss of kyphosis correction from immediate post-operation to most recent
      follow-up was -11.51 degrees  and -9.51 excluding the two failures (P < 0.0001).
      Average pre-operative to most-recent follow-up kyphosis correction was 3.72
      degrees  (P = 0.067) and 5.51 degrees  excluding failures (P = 0.0024). At
      initial one-month follow-up, average disability score was 52.63% (range 16% to
      84%). At most recent follow-up, average disability score was 5.5% (range 0% to
      16%). One patient was lost to long-term follow-up. Mean difference from one-month
      follow-up to most recent follow-up (excluding failures) was 47.27% (P < 0.0001).
      CONCLUSIONS: Short same-segment fixation decreases implantation failure rate and
      reoperation rate compared to traditional SSPF, however long-term kyphosis
      correction was not maintained. Despite this loss of kyphosis correction, clinical
      pain and disability improved at long-term follow-up.

PMID- 22413101
TI  - Betel nut chewing in Hawai'i: is it becoming a public health problem? Historical
      and socio-cultural considerations.
AB  - This article examines the socio-cultural significance of betel nut use among
      Micronesians, in light of the recent migration of Micronesians to Hawai'i. The
      different ways of chewing betel nut are the result of historical changes within
      Micronesia over time due to Spanish and US colonialism as well as the
      introduction of tobacco. These divergent ways of chewing may have different risks
      or impacts on health and it remains to be seen whether or not betel nut will
      become a significant public health problem in Hawai'i.

PMID- 22413102
TI  - Investigating the joys and challenges of rural medicine: a student perspective.

PMID- 22413103
TI  - Student internships at the University Hawai'i Cancer Center.

PMID- 22413105
TI  - Sources and resources for oncologists to help answer the question: is PET/CT
      appropriate for my patient?
AB  - Positron emission tomography (PET)/computed tomography (CT)-subsequently referred
      to as PET/CT is  emerging as a critically important diagnostic tool in oncology.
      There has been a substantial increase in the utilization of this modality over
      the last decade. The optimal imaging protocols are, however, still not
      established which results in considerable confusion and uncertainty among
      referring physicians and providers. Oncologists, hematologists and other
      physicians managing oncologic patients frequently face the dilemma of whether or
      not to order a PET/CT scan for their patients. The large body of evidence from
      clinical research often overwhelms the ability of physicians to stay adequately
      informed on the disease specific performance of PET/CT. Moreover, regulatory
      agencies  have changed their requirements for reimbursement of PET/CT scans in an
      effort to curtail health care expenditures. In this article we attempt to inform
      users and providers about the appropriate use of this  technology.

PMID- 22413106
TI  - Preparation and biological evaluation of paclitaxel loaded biodegradable PCL/PEG
      nanoparticles for the treatment of human neuroendocrine pancreatic tumor in mice.
AB  - The main aim of this study was to develop and evaluate nanoparticulate system of
      paclitaxel loaded polymeric biodegradable Poly (epsilon-caprolactone)
      nanoparticles for targeting to neuroendocrine pancreatic tumors in mice.
      Nanoparticles were prepared by simple emulsion technique having surface
      modification with pluronic F-68. All formulations were evaluated for particle
      shape and size, zeta potential, encapsulation efficiency and in vitro drug
      release. Radiolabelling of nanoparticles with (99m)Tc was done for scintigraphy
      and biodistribution studies. Cytotoxicity studies were performed on BON-1 cell
      line using MTT cell proliferation assay. The in vivo tumor inhibition study was
      performed after i.v. administration of paclitaxel nanoparticles. Our results
      showed that optimized nanoformulation was found to have size range from 100 +/-
      0.03 nm to 250 +/- 0.06 nm with smooth spherical shape. Negative zeta potential
      value confirmed the surface modification and stability of nanoformulations. The
      amount of drug released after 24h from the formulation was found to be 73.3% +/-
      2.7%. More pronounced cytotoxicity was found with nanoparticulate formulation as
      compared with paclitaxel. The PCL-Ptx nanoparticles reduced tumor volume
      significantly in comparison with paclitaxel. Higher concentration of Ptx-NPs were
      found in tumor which was also revealed by high quality scintigraphic image of BON
      1 tumor bearing mouse model. In conclusion, polymeric nanoparticulate formulation
      of paclitaxel was very much efficient for chemotherapy of human pancreatic
      neuroendocrine tumor in mice.

PMID- 22413107
TI  - Swine experimental model to evaluate stem cells implant post myocardial
      infarction by perfusion gated-SPET.
AB  - Autologous bone marrow stromal cells (BMSC) implant after swine experimental
      myocardial infarct (MI) was investigated by serial technetium-99m ((99m)Tc)
      tetrofosmin gated single photon emission tomography (G-SPET) and compared with
      immuno-histochemical findings. The aim was to evaluate if intramyocardial BMSC
      implant produces any prolonged effect in the left ventricle (LV) perfusion and
      function. Eleven pigs underwent left anterior descending artery (LAD) ligature;
      in seven of them BMSC were injected in the border zone of the MI, while in the
      remaining four saline solution was injected at the same site. After LAD ligature
      G-SPET scans at 48h and at 5 and 10 weeks (w) after the implant were performed.
      Uptake defect size and LV function analysis were performed comparing 48h to 5w
      and 10w studies. Statistical evaluation was performed with Friedman test and
      unpaired Wilcoxon test. The comparison between a progressive reduction of
      Perfusion Image Score was observed from 48h to 5w and to 10w in the treated group
      (Friedman test: chi2= 13.56; P=0.01). No variation was observed in the control
      group (Friedman test: chi2=3; P= 0.223). Comparison of the absolute variation
      (Delta) between treated and control group resulted significant (Wilcoxon test
      W=10; P=0.007). Similar positive results were also observed for the relative
      extension of the uptake defect, wall motion and LVEF analysis. Histological data
      of our swine model demonstrated that autologous BMSC implanted in the damaged
      myocardium area had survived and differentiated into cells with typical features
      of myocardiocytes. Gated SPET is a reliable tool to evaluate prolonged positive
      effects of autologous BMSC implant in swine experimental MI model. In conclusion,
      autologous BMSC implanted can improve perfusion, induce cell regeneration, reduce
      wall motion abnormalities and prevent severe LV dysfunction in swines.

PMID- 22413108
TI  - Positron emission tomography in the prediction of inflammation in children with
      human immunodeficiency virus related bronchiectasis.
AB  - There is a lack of objective tools to reliably diagnose exacerbations in
      bronchiectasis. The primary aim of this study was to assess the ability of
      fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography
      (18F-FDG PET/CT) to detect sites of active inflammation in children with human
      immunodeficiency virus (HIV)-related bronchiectasis with or without
      exacerbations. The secondary aim was to assess whether 18F-FDG-PET/CT results are
      in agreement with local and systemic inflammatory markers and markers of HIV
      disease activity. Forty-one children with HIV-related bronchiectasis underwent
      18F-FDG PET/CT. Data on the presence of a clinical exacerbation were recorded.
      Serum was collected for CD4 count, HIV viral load, C-reactive protein (CRP) and
      cytokines IL-8, INF-gamma and TNF-alpha. Induced sputum samples were processed
      for microbiological culture and for IL-8, INF-gamma and TNF-alpha.Mean age of all
      children was 8.2 +/- 2.2 years. Twelve subjects showed F-FDG lung uptake while
      six of them had an exacerbation. There was no difference in the 18F-FDG uptake in
      participants with or without an exacerbation (P=0.613). Fluorine- 18-FDG-PET had
      a good correlation with the presence of consolidation (P=0.01, OR=6.67). The mean
      CRP was higher in the subjects with (18)F-FDG uptake when compared to those
      without uptake (51.96 +/- 95.12 vs. 13.26 +/- 19.87), although this difference
      was not significant (P=0.09). In conclusion, the 18F-FDG-PET lung uptake
      technique could not reliably predict the presence of an exacerbation in children
      with HIV and bronchiectasis, and its diagnostic value was limited to identifying
      disease activity on the scan in acute pneumonia cases. Fluorine-18-FDG-PET had no
      significant correlation with CRP or with other inflammatory biomarkers and
      markers of HIV disease activity.

PMID- 22413109
TI  - The Fukushima nuclear accident temporarily increased patients reluctance for
      nuclear medicine investigations.
AB  - Only mentioning the word "nuclear" already creates anxiety and distress. We
      attempted to assess the impact of the media hype about the Fukushima event on
      patients admitted in nuclear medicine units to undergo diagnostic investigations.
      The number of patients denying scintigraphic studies over half a year after the
      Fukushima accident was compared with the same period of the 2 previous years 2009
      and 2010. Data were separately analyzed into thyroid vs. other organ
      scintigraphies. Physicians' referrals to nuclear medicine showed no decline.
      Patients undergoing various organ scintigraphies asked questions related to the
      accident but only few of them denied the investigation. Questioning and denial
      for nuclear medicine tests were more frequent in females as compared to males and
      especially in child-bearing females. Among patients referred in the initial post
      event phase for thyroid function tests, more than 10% denied thyroid scintigraphy
      and 2.75% questioned this test. Again, questioning and denial was higher with
      females, especially in child-bearing age. In conclusion, this study showed that
      nuclear accidents and perhaps irresponsible media reports may affect behaviour of
      patients referred for nuclear medicine studies and in particular for thyroid
      scintigraphy even if these accidents had no radioactive effect to them.

PMID- 22413110
TI  - Quantitative assessment of crystal material and size on the performance of
      rotating dual head small animal PET scanners using Monte Carlo modeling.
AB  - In this work, among different proposed designs we have studied dual-head
      coincidence detectors (DHC) with pixelated crystals in order to optimize the
      design of detector systems of small animal PET scanners. Monte Carlo simulations
      and different detector components and materials, under different imaging
      conditions and geant 4 application for tomographic emission (GATE) were used for
      all simulations. Crystal length and inter material space on system performance
      were studied modeling several pixel sizes, ranging from 0.5 x 0.5mm2 to 3.0 x
      3.0mm2 by increment of 0.5mm and using epoxy intermaterial with pitch of 0.1, 0.2
      and 0.3mm. Three types of scintillator crystals:bismuth germinate orthosilicate,
      cerium-doped lutetium orthosilicate and gadolinium orthosilicate were simulated
      with thicknesses of 10mm and 15 mm. For all measurements a point source with the
      activity of 1MBq was placed at the center of field of view. The above simulation
      revealed that by increasing pixel size and crystal length in scintillator
      material of a pixelated array, sensitivity can be raised from 1% to 7%. However,
      spatial resolution becomes worse when pixel size increases from 0.6mm to 2.6mm.
      In addition, photons mispositioned events decrease from 76%to 45%. Crystal length
      decrease, significantly reduces the percentage of mispositioned events from 89%
      to 59%. Moreover increase in crystal length from 10mm to 15 mm changes
      sensitivity from 2% to 6% and spatial resolution from 0.6mm to 3.5mm. In
      conclusion, it was shown that pixel size 2mm with 10mm crystal thickness can
      provide the best dimensions in order to optimize system performance. These
      results confirmed the value of GATE Monte Carlo code, as being a useful tool for
      optimizing nuclear medicine imaging systems performance, for small animal PET
      studies.

PMID- 22413111
TI  - The effect of an iodine restricted including no sea foods diet, on technetium-99m
      thyroid scintigraphy: a neglected issue in nuclear medicine practice.
AB  - Although it is recommended to patients to avoid sea food and iodine-containing
      medications prior to iodine-131 (131I) scanning, the efficacy of this diet as for
      technetium-99m pertechnetate ((99m)Tc-P) thyroid scintigraphy is not well
      addressed in the literature. We evaluated a self-managed, outpatients, iodine
      restricted diet (IRD) designed to reduce total body iodine in preparation for
      such a scan. We have studied 39 patients who referred to our Department for
      multinodular goiter, 30 females and 9 males, aged:14-54 years and their (99m)Tc-P
      thyroid scintigraphy showed poor visualization of the thyroid gland. These
      patiens were living in regions with high consumption of sea foods went underwent
      a two-weeks iodine restriction including restriction of sea food diet for the
      reduction of iodine body content. These patients were called for a repeated scan
      after going on a IRD for at least two weeks. The two scans were compared
      visually, and by semiquantitative analysis. Semiquantitative analysis was applied
      in 8 regions of interest (ROI) by using Wilcoxon signed rank test. Thirty-six
      subjects had better quality scintigraphy images in the post IRD thyroid scan, as
      was visually assessed by two nuclear medicine physicians. Semiquantitatetively,
      there was a significant difference in the mean counts of ROI of the right and the
      left thyroid lobes in favor of the post IRD scans (P<0.05). In conclusion, this
      study suggests that in patients with multinodular goiter, living in regions with
      high consumption of sea foods a two-weeks diet for the reduction of iodine body
      content induces in most of the cases a slightly better diagnostic thyroid (99m)Tc
      P scan.

PMID- 22413112
TI  - Preperation of (99m)Tc labeled 5-fluorouracil as a potential diagnostic agent in
      advanced breast cancer: first clinical trial.
AB  - The chemotherapeutic drug 5-fluorouracil (5FU) is used for treatment of various
      types of cancers. The present study was conducted to evaluate the potential of
      this drug as a diagnostic radiopharmaceutical in advanced breast cancer. We have
      labeled 5FU by using the stannous chloride reduction method with 555MBq of
      technetium-99m ((99m)Tc). The (99m)Tc-5FU was injected intravenously in 4
      patients having advanced breast cancer. Dynamic and static images were taken at
      various time intervals till 2h. Whole body images were used to calculate the
      percentage of the injected dose, in each organ. Target to non target ratio was
      calculated to find out the optimum time for imaging. In conclusion, our study
      showed that (99m)Tc-5FU was a promising agent for diagnosing advanced breast
      cancer with optimum visualization at 1h.

PMID- 22413113
TI  - A chemical model suggesting the maximum radiolabeled somatostatin analogue tumor
      uptake, in the presence of unlabeled somatostatin.
AB  - Somatostatin analogues (SSA), both radiolabeled and unlabeled play an important
      role in the management of carcinoid tumors. They are often administered in
      parallel, the unlabeled analogue for treating the carcinoid tumors' symptoms and
      the radiolabeled one for imaging tumors foci. There is a debate about when is the
      optimum time for a somatostatin receptor scintigraphy during treatment. Opinions
      are divided, with some authors suggesting stopping SSA treatment, while others do
      not. Our aim was to try to explore pharmacokinetics behind the radiolabeled
      peptide administration in the presence of circulating in blood unlabeled SSA, by
      using a model of "law of mass". Applying the pharmacokinetic data from the
      manufacturers' Prescription Information Sheet in a formula describing competitive
      binding, led to a reduced uptake for the radiolabeled peptide in the presence of
      the unlabeled peptide, in comparison with standalone radiolabeled peptide
      administration, regardless of the total number of available receptors. We provide
      data that unlabeled somatostatin should be withdrawn for no less than 14 days
      before the labeled SSA is administered, because biotherapy agents interfere with
      both diagnostic and therepeutic nuclear medicine procedures. Further research is
      needed to reach secure conclusions on patient medication management before
      diagnostic scans or therapeutic administrations in nuclear medicine. In
      conclusion, by waiting at least 6 half-lives (14 days), after the unlabeled SSA
      administration, the radiolabeled receptor uptake increased two-fold to three
      fold, as compared to simultaneous administration of radiolabeled and unlabeled
      peptides depending on which SSA was used.

PMID- 22413114
TI  - Scintigraphy and computed tomography findings for the diagnosis of bronchiolitis
      obliterans following peripheral blood stem cell transplantation.
AB  - We report a case of bronchiolitis obliterans (BO) associated with allogenic
      peripheral blood stem cell transplantation for acute leukemia. On inspiratory and
      expiratory chest computed tomography (CT), characteristic findings for BO, such
      as air-trapping, mosaic attenuation or bronchial wall thickening were not clearly
      observed. However, ventilation-perfusion lung scans of the chest demonstrated
      multiple matched defects, which suggested severe obstructive airway disease. In
      the diagnosis of BO after stem cell transplantation, lung scans should be
      recommended when representative findings are not obvious on chest CT.

PMID- 22413115
TI  - Three synchronous primary tumors with different histology detected by 18F-FDG
      PET/CT.
AB  - The aim of this study is to present a patient with 3 primaries diagnosed with the
      18F-FDG PET/CT study performed for the staging of endometrial cancer. Pathologic
      accumulations of the tracer were detected in both lobes of the thyroid gland, in
      the left lung and in the known primary of the uterus. A bilateral multifocal
      differentiated thyroid carcinoma and a peripheral carcinoid tumor in left lung
      were the final diagnosis as shown by histology. In conclusion, in this patient
      the PET/CT study performed for staging endometrial cancer demonstrated two new
      synchronous primary tumors. This is the second similar case but the first where
      all three primaries had entirely different histology.

PMID- 22413116
TI  - Emotional impairment in a patient with amyotrophic lateral sclerosis: a (99m)Tc
      HMPAO SPET brain study.
AB  - Behavioral abnormalities have been reported in patients with amyotrophic lateral
      sclerosis (ALS) but their aetiology is not yet clearly defined. We report on the
      case of a 48 years old woman with long standing bulbar onset ALS referred to our
      department for brain perfusion scan for the evaluation of behavioral and
      emotional disorders. The patient's scores on the neuropsychological tests were
      satisfactory while magnetic resonance imaging showed no structural brain
      abnormalities. However, cerebral blood flow imaging with single photon emission
      tomography with technetium-99m-hexamethyl propylamine oxime demonstrated
      bilateral frontal cortex hypoperfusion, as well as perfusion defects in the left
      parietal, temporal and occipital lobes. In conclusion, the reduced regional
      cerebral blood flow in the frontal lobes might be suggestive of underlying
      cortical disturbance and potentially explain the patient's symptoms.

PMID- 22413117
TI  - Incidental detection and monitoring of spontaneous recovery of sarcoidosis via
      fluorine-18-fluoroethyl-choline positron emission tomography/computed tomography.
AB  - We report a case of sarcoidosis detected incidentally by using fluorine-18
      fluoroethylcholine- positron emission tomography/computed tomography (18F-FECH
      PET/CT) in a 72 years old patient with prostate cancer, who had been referred for
      restaging after relapse indicated prostate specific antigen (PSA). The 18F-FECH
      PET/CT examination showed a focal increased uptake in the prostate bed suggestive
      for local recurrence, in addition to multifocal uptake in the mediastinum
      matching with enlarged hilar and paratracheal lymph nodes. Histopathology
      revealed sarcoidosis. No treatment was recommended. Two years later the patient
      was referred again to us because of another recurrent PSA elevation. The second
      18F-FECH-PET/CT showed again the previously described local recurrence, but did
      not show the previously described mediastinal findings nor the enlarged hilar and
      paratracheal lymph nodes, thus, illustrating spontaneous healing of sarcoidosis.
      In conclusion, this case suggests that 18F-FECH PET/CT study can show positive
      findings in sarcoidosis that were no longer detectable after two years,
      suggestive of spontaneous recovery.

PMID- 22413118
TI  - Furosemide increases thyroid uptake of radioiodine in an anuric patient: first
      observation.

PMID- 22413119
TI  - First description of the role of 18F-FDG-PET/CT as compared to CT, MRI to suspect
      a case of thymoma in a pediatric patient.

PMID- 22413120
TI  - (18)F-FDG-PET assessment of early treatment response of articular and extra
      articular foci in newly diagnosed rheumatoid arthritis.

PMID- 22413121
TI  - Acute respiratory distress syndrome suggested by 18F-FDG PET/CT.

PMID- 22413122
TI  - Thalamic 123I FP-CIT uptake in a patient with clinical diagnosis of Parkinson's
      disease and depression.

PMID- 22413123
TI  - Neuroimaging in mild traumatic brain injury and M. Ravel's injury.

PMID- 22413124
TI  - Metal-based impurities in graphenes: application for electroanalysis.
AB  - We show here that metallic impurities presented in graphenes prepared from
      graphite can be usefully employed for electroanalysis. We demonstrate that cumene
      hydroperoxide electrochemical reduction on graphene containing iron-based
      impurities provides significantly larger voltammetric currents than the same
      experiment using iron oxide nanoparticles. This opens doors for turning metallic
      impurities into potentially useful components of graphene based electrochemical
      systems.

PMID- 22413125
TI  - Free-standing liposomal nanohybrid cerasomes as ideal materials for sensing of
      cupric ions.
AB  - Super-stable and free-standing cerasomes with inorganic polyorganosiloxane
      surfaces were developed for the sensing of Cu(2+) by encapsulating Nile red (NR)
      dye as a fluorescence reporter. 1,2-Dimynistoyl-sn-glycero-3
      phosphatidylethanolamine (DMPE) was incorporated into the cerasomes to serve as
      the chelating agent for cupric ions. The intraparticle energy transfer from NR to
      Cu(2+) caused the fluorescence quenching of NR, showing the prospect of these
      cerasomes as a fluorescence "turn-off" sensor for the detection of trace copper
      ions.

PMID- 22413126
TI  - Thickness dependent sensing mechanism in sorted semi-conducting single walled
      nanotube based sensors.
AB  - Single walled carbon nanotube (SWCNT) networks present outstanding potential for
      the development of SWCNT-based gas sensors. Due to the complexity of the
      transport properties of this material, the physical mechanisms at stake during
      exposure to gas are still under debate. Previously suggested mechanisms are
      charge transfer between gas molecules and SWCNT and Schottky barrier modulation.
      By comparing electrical measurements with an analytical model based on Schottky
      barrier modulation, we demonstrate that one mechanism or the other is predominant
      depending on the percolation of metallic carbon nanotubes. Below the metallic
      SWCNT percolation threshold, sensing is dominated by the modulation of the
      Schottky barrier, while above this threshold, it is only attributed to a charge
      transfer between SWCNT and gas molecules. Both mechanisms are discussed in terms
      of sensitivity and resolution leading to routes for the optimization of a gas
      sensor architecture based on highly enriched semiconducting carbon nanotube
      films.

PMID- 22413127
TI  - A simple fluorometric assay for DNA exonuclease activity based on graphene oxide.
AB  - A new assay platform for DNA exonuclease activity is developed based on the
      preferential binding of single-stranded DNA (ssDNA) over double-stranded DNA
      (dsDNA) to graphene oxide. This approach allows a simple and quantitative
      activity measurement in a short time at low cost.

PMID- 22413128
TI  - Rapid visual detection of aluminium ion using citrate capped gold nanoparticles.
AB  - We report the visual detection of Al(3+) using unlabeled gold nanoparticles
      (AuNPs) based on the complexation of Al(3+) with citric acid, resulting in the
      aggregation of AuNPs. The distinction of color change can be observed by the
      naked eye at concentrations down to 1.0 MUM which is lower than the permissable
      level (7.4 MUM) for drinking water as defined by the World Health Organization.

PMID- 22413129
TI  - [Accidental fall from the swing].

PMID- 22413130
TI  - Small, first in man, trial of rituximab for ulcerative colitis.

PMID- 22413131
TI  - Yeast-like intraleukocytic inclusions in a peripheral smear.

PMID- 22413132
TI  - Milling effect on the control efficacy of spray-dried Bacillus  thuringiensis
      technical powder against diamondback moths.
AB  - BACKGROUND: The relationship between the particle size of spray-dried Bacillus
      thuringiensis NT0423 technical powder and its insecticidal activity against
      diamondbackmoth was investigated in laboratory and glasshouse conditions. A
      variety of sizes of Bt particles were made by homogenisation, followed by pilot
      scale milling to optimise further the current Bt formulation process. RESULTS: In
      laboratory conditions, homogenised Bt suspension with smaller particles had
      higher control efficacy against diamondback moth. However, in glasshouse
      conditions, the smallest particle treatment did not follow the size-dependent
      insecticidal activity, rather showing decreased control efficacy. Secondly, air
      jet-milled Bt powder (16.9 MUm) had higher control efficacy than hammer-milled Bt
      powder (35.1 MUm) in glasshouse conditions. However, double air-jet milling (5.3
      MUm) had lower control efficacy compared with one-time milling. CONCLUSION: These
      results suggest that NT0423 technical powder with smaller particles is better in
      controlling diamondback moths, but excessively small particles (<10 MUm) possibly
      reduce the insecticidal activity.

PMID- 22413133
TI  - [Not Available].

PMID- 22413134
TI  - [Not Available].

PMID- 22413135
TI  - [Not Available].

PMID- 22413136
TI  - Retraction notice. "EPCA-2: a highly specific serum marker for prostate cancer"
      by Leman et al (Urology 2007;69:714-720).

PMID- 22413137
TI  - III Congress of physiologists of CIS "Physiology and Human Health". Dedicated to
      the memory of academician PG Kostiuk, October 1-6, 2011, Ialta, Ukraine.

PMID- 22413138
TI  - [Abstracts to the All-Ukrainian Conference of Young Scientists "Physiology-from
      Molecules to the Body", October 20-21, 2011.

PMID- 22413139
TI  - Japan's Tohoku earthquake: 1 year on.

PMID- 22413140
TI  - Panel meeting prompts excitement for antiobesity drug.

PMID- 22413141
TI  - Costa Rica restructures health system to curb financial crisis.

PMID- 22413142
TI  - Knowing its place: mapping as medical investigation.

PMID- 22413143
TI  - Aroma characterization of tangerine hybrids by gas-chromatography-olfactometry
      and sensory evaluation.
AB  - BACKGROUND: Tangerines have a distinct flavor among citrus fruit. However,
      information on tangerine volatiles remains limited. Volatile compounds from a
      breeding population of tangerines were earlier identified by gas chromatography
      mass spectrometry. In this study, five hybrids with a distinct volatile profile
      were analyzed by gas-chromatography-olfactometry (GC-O) and descriptive sensory
      analysis. RESULTS: Forty-nine aroma active compounds were found in a consensus by
      GC-O. Aldehydes were the most important group with odor activity, as well as
      monoterpenes, esters, alcohols and ketones. 1,8-Cineole, beta-myrcene, (E,E)-2,4
      nonadienal, hexanal, ethyl-2-methylbutanoate, and linalool were perceived with
      high intensity in most samples. Two 'Clementine' * 'Minneola' and one 'Fortune' *
      'Murcott' hybrids with tangerine, sulfury and woody/spicy flavors had aroma
      active compounds with terpeney, fatty/vegetable and metallic/rubber descriptors.
      A tangerine with 'Valencia' orange in its parentage had a characteristic orange
      flavor, which could be explained by esters and ketones, high in fruity and floral
      odor intensities. A hybrid of unknown origin had a distinct fruity-non-citrus and
      pumpkin/fatty flavor; that sample had the lowest amount of aroma-active
      volatiles, with the least compounds with terpeney odors. CONCLUSION: There was no
      one compound characteristic of tangerine flavor. Nevertheless, each sample
      sensory characteristic could be explained by a set of aroma-active volatile
      compounds.

PMID- 22413144
TI  - An investigation into gamma-ray treatment of shellfish using electron
      paramagnetic resonance spectroscopy.
AB  - BACKGROUND: Gamma irradiation is a safe method for the decontamination of
      shellfish, and its technical feasibility and safety have been endorsed
      (FAO/IAEA/WHO). In order to implement proper food-processing regulations, the
      identification of radiation treatment is required. In this study, electron
      paramagnetic resonance (EPR) spectroscopy was employed to identify the
      irradiation of seven different types of commonly consumed shellfish. RESULTS:
      Characteristics (g factor and signal intensity) of the EPR spectra of control and
      irradiated samples were recorded in order to clarify the gamma-ray treatment of
      shellfish. Radiation-specific signals around g = 2.0038 +/- 0.0006 (g1) and g =
      1.9996 +/- 0.0002 (g2 and g3) were observed for all shellfish samples irradiated
      with absorbed doses of 3 and 6 kGy. The X-ray diffraction (XRD) spectra of some
      shellfish samples were recorded to investigate their mineral profiles.
      CONCLUSION: The EPR spectroscopic results indicated that carbonate minerals were
      the source of the paramagnetic species that were produced upon irradiation,
      entrapped in the shellfish and showed radiation-specific asymmetric signals whose
      intensities increased quantitatively with the absorbed radiation dose. The XRD
      analysis revealed that aragonite and calcite minerals were present in the shells
      of shellfish.

PMID- 22413145
TI  - Comparative study on protein cross-linking and gel enhancing effect of microbial
      transglutaminase on surimi from different fish.
AB  - BACKGROUND: Microbial transglutaminase (MTGase) has been used to increase the gel
      strength of surimi. Nevertheless, its effectiveness varies with fish species. The
      aim of this study was to elucidate the effect of MTGase at different levels on
      protein cross-linking and gel property of surimi from threadfin bream, Indian
      mackerel and sardine in the presence and absence of endogenous transglutaminase.
      RESULT: Breaking force of all surimi gels increased as MTGase levels (0-0.6 U g
      1) increased except for threadfin bream surimi gel, where the breaking force
      decreased at 0.6 U g-1 (P < 0.05). In the presence of EDTA, the gel strengthening
      effect was lower, suggesting the combined effect of endogenous transglutaminase
      with MTGase. With the addition of MTGase, the gel with the highest increase in
      breaking force showed highest decrease in myosin heavy chain. When cross-linking
      activity of MTGase on natural actomyosin (NAM) was determined, the highest
      decreasing rate in epsilon-amino group content with the concomitant increased
      formation of cross-linked proteins was found in NAM from threadfin bream. The
      reactivity of muscle proteins toward MTGase-induced cross-linking was in
      agreement with surimi gel strengthening. CONCLUSION: The composition and
      properties of muscle proteins of varying fish species more likely determined
      protein cross-linking induced by MTGase, thereby affecting their gel properties.

PMID- 22413146
TI  - Using ITS2 PCR-RFLP to generate molecular markers for authentication of Sophora
      flavescens Ait.
AB  - BACKGROUND: Dried root of Sophora flavescens Ait. is a medicinal material
      occasionally misused or adulterated by other species similar in appearance. In
      this study the internal transcribed spacer (ITS) regions of DNA samples of S.
      flavescens Ait. collected from different areas of Taiwan were amplified by
      polymerase chain reaction (PCR) and compared. The effectiveness of using ITS2 PCR
      restriction fragment length polymorphism (RFLP)-generated markers to
      differentiate S. flavescens Ait. from possible adulterants was also evaluated.
      RESULTS: The S. flavescens Ait. samples collected from different areas were
      extremely low in ITS sequence variability at species level. ITS2 PCR-RFLP coupled
      with restriction enzymes Sac I, Sac II, Xho I or Pvu I produced specific
      fragments for all tested variants. ITS2 PCR-RFLP coupled with Sac II was further
      performed to identify mixtures of DNA extracts of S. flavescens Ait. and Sophora
      tomentosa L. in various ratios. The developed ITS2 PCR-RFLP markers could detect
      mixed DNA samples of S. flavescens Ait./S. tomentosa L. up to a ratio of 10:1.
      CONCLUSION: The present study demonstrates the usefulness of ITS2 PCR-RFLP
      coupled with pre-selected restriction enzymes for practical and accurate
      authentication of S. flavescens Ait. The technique is also suitable for analysing
      S. flavescens Ait. mixed with other adulterants.

PMID- 22413147
TI  - Effects of cinnamon leaf, oregano and sweet orange essential oils on fermentation
      and aerobic stability of barley silage.
AB  - BACKGROUND: Silage additives are marketed with the primary aim of improving the
      fermentation and/or aerobic stability of silage. The objective of this study was
      to evaluate the impact of three different essential oils (EOs; cinnamon leaf
      (CIN), oregano (ORE) and sweet orange (SO)) on the fermentation characteristics
      and stability of barley silage. Chopped whole-plant barley (Hordem vulgare L.)
      forage was ensiled either untreated (0 mg kg-1 dry matter (DM)) or treated with
      CIN, ORE or SO (37.5, 75 and 120 mg kg-1 DM). RESULTS: Moulds were not detected
      in any treatments, including the control, after 7 days of air exposure. All EOs
      at a concentration of 120 mg kg-1 silage DM decreased (P = 0.001) yeast
      populations in comparison with the control during air exposure. Net gas, methane
      and ammonia concentrations in vitro did not differ among treatments. Changes in
      volatile fatty acid concentrations were small, and in situ data showed no changes
      in DM and neutral detergent fibre digestion rates for CIN, ORE or SO at
      concentrations up to 120 mg kg-1 DM. CONCLUSION: The findings from this study
      show that a concentration of 120 mg EO kg-1 DM decreased yeast counts during
      aerobic stability tests. However, all EO treatments had minimal effects on data
      from in vitro and in situ incubations.

PMID- 22413149
TI  - A rapid method to regenerate piezoelectric microcantilever sensors (PEMS).
AB  - Piezoelectric microcantilever sensors (PEMS) can be sensitive tools for the
      detection of proteins and cells in biological fluids. However, currently
      available PEMS can only be used a single time or must be completely stripped and
      refunctionalized prior to subsequent uses. Here we report the successful use of
      an alternative regeneration protocol employing high salt concentrations to remove
      the target, leaving the functional probe immobilized on the microcantilever
      surface. Our model system employed the extracellular domain (ECD) of recombinant
      human Epidermal Growth Factor Receptor (EGFR) as the probe and anti-human EGFR
      polyclonal antibodies as the target. We report that high concentrations of MgCl2
      dissociated polyclonal antibodies specifically bound to EGFR ECD immobilized on
      the sensor surface without affecting its bioactivity. This simple regeneration
      protocol both minimized the time required to re-conjugate the probe and preserved
      the density of probe immobilized on PEMS surface, yielding identical biosensor
      sensitivity over a series of assays.

PMID- 22413150
TI  - Factors associated with triptan use in episodic migraine: results from the
      American Migraine Prevalence and Prevention Study.
AB  - BACKGROUND: Though triptans are considered the standard of acute therapy for
      migraine attacks with headache-related disability, they are used by the minority
      of potentially eligible persons. Understanding the socio-demographic and headache
      features that predict triptan use may help to clarify barriers to optimal
      treatment. OBJECTIVE: To assess the sociodemographic and headache features
      associated with triptan use in a US population sample of persons with episodic
      migraine. METHODS: The American Migraine Prevalence and Prevention Study (AMPP)
      is a longitudinal study conducted in a representative sample of US headache
      sufferers. Episodic migraineurs (n = 11,388) who provided treatment data in 2005
      were included in the current analyses.We assessed factors associated with triptan
      use through univariate and multivariate analyses. Multivariate analyses were
      adjusted for sociodemographic factors, headache-related disability, cutaneous
      allodynia, depression, and preventive headache medication use. RESULTS: Among
      persons with episodic migraine, 18.31% reported current use of triptans for acute
      headache treatment. In univariate analyses, triptan use was most common in
      midlife (ages 30-59), among females, and was more common in Caucasians than in
      African Americans. Triptan use increased with headache frequency, headache
      related disability and allodynia, but decreased among persons with depression. In
      multivariate analyses, female gender, Caucasian race, age 40-49, higher levels of
      education (college or higher), annual household income of >=$40,000, having
      health insurance, the presence of cutaneous allodynia, greater headache-related
      disability, and preventive medication use for migraine were significantly
      associated with triptan use. CONCLUSIONS: Less than 1 in 5 persons with migraine
      in the United States who were respondents to this survey used triptans for acute
      headache treatment over the course of a year. Several markers of severe headache,
      including disability and allodynia,were associated with increased triptan use.
      Groups less likely to get triptans included males, African Americans, older
      adults, and the uninsured. Predictors of use provide insight into groups with
      unmet treatment needs.

PMID- 22413152
TI  - [The diagnostics of the obstructive jaundice and possibilities to improve the
      efficacy of its miniinvasive treatment].
AB  - The study, which included data of 226 patients with the obstructive jaundice,
      proved, that the clinical presentation and laboratory tests have secondary role
      in diagnosing the level of the biliary block. Among diagnostic means of detecting
      the etiology of the obstruction were the ultrasound investigation (n=268); the
      magnetic resonance cholangiopanreatography (n=143); the multispiral computed
      tomograpth (n=119); the endoscopic retrograde cholangiopanreatography (n=187) and
      the transcutaneous transhepatic cholangiopanreatography (n=69). Flaws and pros of
      all the methods were thoroughly analyzed. The endoscopic (n=172) and
      transcutaneous transhepatic cholangiostomy (n=87) were used for biliary
      decompression. The comparative analysis of both diagnostic and treatment means
      allowed the creation of 3-stage algorithm. The efficacy of the last for patients
      with the obstructive jaundice was 96%.

PMID- 22413153
TI  - [The results of different types of cholecystectomy in elderly patients].
AB  - Treatment results of 1048 elderly patients, operated on the cholelithiasis, were
      analyzed. The group of minilaparotomic access cholecystectomy numbered 488
      (46,6%) patients; the second group consisted of 560 (53,4%) patients, who had the
      traditional operation. All patients were operated on in a single hospital during
      1998-2008 yy. The cholecystectomy from minilaparotomic access proved to be less
      traumatic and preferable for elderly patients. The rate of postoperative
      morbidity was 5,7%, mortality - 0,2%. The procedure, though, is subjected to the
      experienced surgeons.

PMID- 22413151
TI  - A randomized trial of a web-based intervention to improve migraine self
      management and coping.
AB  - OBJECTIVE: To test the clinical efficacy of a web-based intervention designed to
      increase patient self-efficacy to perform headache self-management activities and
      symptom management strategies, and reduce migraine-related psychological
      distress. BACKGROUND: In spite of their demonstrated efficacy, behavioral
      interventions are used infrequently as an adjunct in medical treatment of
      migraine. Little clinical attention is paid to the behavioral factors that can
      help manage migraine more effectively and improve the quality of care and quality
      of life. Access to evidenced-based, tailored, behavioral treatment is limited for
      many people with migraine. DESIGN: The study is a parallel group design with 2
      conditions: (1) an experimental group exposed to the web intervention; and (2) a
      no-treatment control group that was not exposed to the intervention. Assessments
      for both groups were conducted at baseline (T1), 1-month (T2), 3-months (T3), and
      6-months (T4). RESULTS: Compared with controls, participants in the experimental
      group reported significantly: increased headache self-efficacy, increased use of
      relaxation, increased use of social support, decreased pain catastrophizing,
      decreased depression, and decreased stress. The hypothesis that the intervention
      would reduce pain could not be tested. CONCLUSIONS: Demonstrated increases in
      self-efficacy to perform headache self-management, increased use of positive
      symptom management strategies, and reported decreased migraine-related depression
      and stress suggest that the intervention may be a useful behavioral adjunct to a
      comprehensive medical approach to managing migraine.

PMID- 22413154
TI  - [The preoperative thoracic X-ray for tactical decisions for the thoracic injuries
      treatment].
AB  - Data of 379 patients with penetrating thoracic wounds were analyzed. The
      pathologic changes on X-ray of the thoracic cavity were registered 239 (63,1%)
      patients: the hemothorax was diagnosed in 44,3%, pneumothorax - in 26,8% and
      hemopneumothorax - in 28,9%. 154 patients had videothoracoscopic surgery and 225
      patients were operated on using traditional open methods. Operative findings were
      compared with X-ray data. The sensitivity of plain chest radiography in
      diagnostics of hemothorax was 52,1%, the specificity - 92,1%. Mistakes of
      interpreting X-ray data in diagnosing of low-volume hemo- or pneumothorax were
      defined. The computed tomography of the thorax proved to be the most precise
      means of intrapleural injuries diagnostics. The optimal algorithm of preoperative
      thoracic X-ray was suggested.

PMID- 22413155
TI  - [The diagnostics and treatment of the postoperative mediastinitis].
AB  - Treatment results of 48 patients with mediastinitis after the open cardiac
      surgery were analyzed. The main mediastinitis risk factors were: the chronic
      obstructive lung desease, diabetes mekkitus, severe cardiac insufficiency,
      prolonged operation, the use of artificial blood circulation and sterna
      instsbility. Major infective agents of mediastinitis were the Gram-positive
      cocci. The treatment options varied from the prolonged antibiotic therapy to
      plastic reconstructive surgery, which were determined by the severity of
      mediastinitis.

PMID- 22413156
TI  - [The ileal and colic microcirculation by the thrombosis and thromboembolism of
      mesenterial arteries].
AB  - Quantitative and functional parameters of regional intestinal blood circulation
      were intraoperatively investigated with the use of laser Doppler flowmetry. The
      first group consisted of patients with necrotized parts of the intestine, while
      the second (control) group consisted of flowmetry data from intact intestine.
      Such indexes, as basal circulation, variation coefficient, blood oxygen perfusion
      saturation index, maximal perfusion amplitude of endothelial, neurogenic and
      myogenic oscillations in the intestinal volume, were showed to be valuable for
      the intestinal viability assessment. Thus, the method of the intraoperative laser
      Doppler flowmetry can be useful for determining the volume of intestinal
      resection.

PMID- 22413157
TI  - [The complex prophylaxis of thromboembolism in oncourologic patients].
AB  - One of the major complications in oncourological patients in the hospital is the
      development of thromboembolic complications. This article is devoted to analysis
      of the results of the comprehensive prevention of thromboembolic complications in
      1006 patients that have received surgical treatment in the Scientific research
      institute of urology in the period 2009-2011. Carried out the comparative
      estimation of efficiency of elastic bandaging and elastic compressive knitted
      wear as a means of non-medicamental prevention of thromboembolic complications in
      of oncourology. In the study, in addition to assessing the impact of elastic
      compression on various aspects of the state of the venous system of patients and
      the hemostasis system is shown that the use of elastic compression hosiery
      compared with elastic bandaging allows to reduce the incidence of thromboembolic
      complications.

PMID- 22413158
TI  - [Miniinvasive technologies in treatment of intraarticular splittered fractures of
      the proximal shoulder].
AB  - The algorithm of diagnostics, miniinvasive ostheosynthesis and postoperative
      rehabilitation of patients with the splittered fractures of caput femori was
      worked out. Treatment results of 24 patients were analyzed. All patients were
      treated with the use of the original apparatus of the external osteal fixation.
      The method allows early functional treatment and limb function restoration in
      cases, when classic immersinal ostheosynthesis is contraindicated.

PMID- 22413159
TI  - [The surgical treatment of the combined diseases of the pelvis].
AB  - 167 women were simultaneously operated on gynecological disease and the combined
      other surgical diseases. Novel methods of laparoscopic surgery, allowing to
      decrease intra- and postoperative complications were represented. Authors proved
      the efficacy and necessity of simultaneous operations.

PMID- 22413160
TI  - [The optimization of surgical treatment of skin and soft tissues defects].
AB  - 75 soft tissue reconstructive surgical procedures in patients with burn
      deformation, traumatic soft tissue defects and soft tissue defects after major
      tumor resections were analyzed. 24 reconstructions were performed with the use of
      local flap method, mostly triangular and trapezium flaps. 39 reconstructions
      involved island and free vascular flaps. The survival of the flaps was obtained
      in 98,6% of cases.

PMID- 22413161
TI  - [The laparoscopic adrenalectomy in children].
AB  - 22 children with tumors or other surgical diseases of the adrenal glands were
      operated on laparoscopically. Children aged from 5 months to 17 years. Operation
      lengths varied from 45 to 190 minutes. There were no lethal outcomes, conversions
      and serious complications of the procedure. Authors consider the laparoscopic
      adrenalectomy to be the safe and widely appropriate method for the use in
      juvenile cathegory of patients.

PMID- 22413162
TI  - [Clinical and morphologic aspects of surgery choice by postoperative
      anterolateral and lateral ventral hernias].
AB  - Clinical picture, diagnostic features and operative techniques in patients with
      postoperative anterolateral and lateral ventral hernias have been analyzed.
      Synthetic endoprosthesis were comparatively tested on human dermal fibroplast
      cell cultures. Taking into account and practical use of the obtained results
      allowed the recurrence rate decrease from 63 to 6%.

PMID- 22413163
TI  - [Bacteriological tests of the operative material in patients with lung
      tuberculosis].
AB  - 64 patients with lung tuberculosis were operated on after chemotherapy course
      using regimens I and III. 69 patients were operated on after the treatment by
      DOTS/PLUS protocol. The obtained operative material was bacteriologically tested.
      Bacterial growth in samples of patients treated with DOTS/PLUS protocol caused by
      multydrug resistance of mycobacteria. The noncoinsidence of the drug resistance
      spectrum in sputum and resected samples was registered in 33% of patients treated
      by DOTS/ PLUS protocol and 25% of patients, treated by using regimens I and III.

PMID- 22413164
TI  - [Etiology and pathogenesis of secondary edema of the lower extremities in
      patients with limited pretibialnoy myxedema on the background of
      hyperthyroidism].
AB  - Results of the examination of patients with secondary lymphedema in the period
      2006-2010. Revealed that the most frequent concomitant diseases in 150 (57,6%)
      patients with secondary lymphostasis lower extremities is hyperthyroidism.
      CLINICAL MANIFESTATIONS: an increase in thyroid size, infiltrative endocrine
      ophthalmopathy; balanced, solid consistency swelling of the lower extremities to
      the level of the upper third of the leg; hyperkeratosis; paresthesias. The
      results of functional studies of the condition of peripheral lymph in patients
      with different stages of secondary lymphostasis lower extremities against a
      background of hyperthyroidism showed a direct relationship between the severity
      of the disease, the degree of decompensation of peripheral lymph and the state of
      thyroid function.

PMID- 22413165
TI  - [The correction of tissue hypoxia and free radical peroxidation by gastroduodenal
      bleedings].

PMID- 22413166
TI  - [The use of modern hemostatics in surgery of long bones' ostheomyelitis and
      prosthetic infections of coxofemoral and knee joints].

PMID- 22413167
TI  - [The bedsore of the stomach and duodenum, caused by the foreign body].

PMID- 22413168
TI  - [The rare localization of the spontaneous external biliary fistula].

PMID- 22413169
TI  - [The laparoscopic cholecystectomy in elderly patients].

PMID- 22413170
TI  - [School Pirogov: prof. V.F. Voyno-Yasenetskiy].

PMID- 22413171
TI  - Geography and global health.
AB  - In the wake of the report of the World Health Organisation's Commission on the
      Social Determinants of Health, Closing the gap in a generation (Marmot 2008),
      this invited commentary considers the scope for geographical research on global
      health. We reflect on current work and note future possibilities, particularly
      those that take a critical perspective on the interplay of globalisation,
      security and health.

PMID- 22413172
TI  - Balancing urban and peri-urban exchange: water geography of rural livelihoods in
      Mexico.
AB  - The peri-urban area is the region where there is a more dynamic interaction
      between the urban and rural. The peri-urban area supplies natural resources, such
      as land for urban expansion and agricultural products to feed the urban
      population. In arid and semi-arid lands, such as northern Mexico, these areas may
      also be the source of water for the city's domestic demand. In addition, scholars
      argue that peri-urban residents may have a more advantageous geographical
      position for selling their labour and agricultural products in cities and, by
      doing so, sustaining their livelihoods. A considerable number of studies have
      examined the peri-urban to urban natural resources transfer in terms of land
      annexation, housing construction, and infrastructure issues; however, the study
      of the effects of the reallocation of peri-urban water resources to serve urban
      needs is critical as well because the livelihoods of peri-urban residents, such
      as those based on agriculture and livestock, depend on water availability. In the
      case of Hermosillo there is a tremendous pressure on the water resources of peri
      urban small farm communities or ejidos because of urban demand. Based on
      interviews and structured surveys with producers and water managers, this paper
      examines how peri-urban livelihoods have been reshaped by the reallocation of the
      city's natural resources in many cases caused some ejido members or ejidatarios
      to lose livelihoods.

PMID- 22413173
TI  - Water demand management in Yemen and Jordan: addressing power and interests.
AB  - This paper investigates the extent to which entrenched interests of stakeholder
      groups both maintain water use practice, and may be confronted. The focus is on
      the agricultural sectors of Yemen and Jordan, where water resource policymakers
      face resistance in their attempts to reduce water use to environmentally
      sustainable levels through implementation of water demand management (WDM)
      activities. Some farmers in both countries that have invested in irrigated
      production of high-value crops (such as qat and bananas) benefit from a political
      economy that encourages increased rather than reduced water consumption. The
      resultant over-exploitation of water resources affects groups in unequal
      measures. Stakeholder analysis demonstrates that the more 'powerful' groups
      (chiefly the large landowners and the political elites, as well as the ministries
      of irrigation over which they exert influence) are generally opposed to reform in
      water use, while the proponents of WDM (e.g. water resource managers,
      environmental ministries and NGOs, and the international donor community) are
      found to have minimal influence over water use policy and decisionmaking. Efforts
      and ideas attempted by this latter group to challenge the status quo are
      classified here as either (a) influencing or (b) challenging the power asymmetry,
      and the merits and limits of both approaches are discussed. The interpretation of
      evidence suggests current practice is likely to endure, but may be more
      effectively challenged if a long-term approach is taken with an awareness of
      opportunities generated by windows of opportunity and the participation of
      'overlap groups'.

PMID- 22413174
TI  - Lost in translation: conflicting views of deforestation, land use and identity in
      western Madagascar.
AB  - This paper focuses on the interplay between environmental narratives, identity
      politics and the management of forest resources in Madagascar. While efforts to
      conserve the island's biological diversity have centred primarily on the
      designation of protected areas, policies have increasingly focused on local
      communities. The experiences of the last 20 years have shown that community-based
      approaches to conservation offer considerable challenges due to the complex
      politics of natural resource use, which involve multiple and diverse
      stakeholders, often with very different and sometimes conflicting values. In this
      paper, I focus on the environmental perceptions and values of two groups in the
      Central Menabe region of western Madagascar - conservation organisations and
      rural households - revealing a contrasting set of views regarding the region's
      forest. I show that the conservation discourse has changed over time,
      increasingly emphasising the biological diversity of the region's tropical dry
      deciduous forest and prioritising non-consumptive uses of natural resources.
      Although policy has changed in response to changing values, I show that it has
      been underpinned by the notion that hatsake ('slash-and-burn' agriculture) is an
      irrational practice driven by necessity rather than choice. Policy has thus
      sought to provide livelihood alternatives, firstly through forestry, then through
      changes in cultivation and increasingly through tourism. This misunderstands the
      local view of the forest, which sees hatsake as a way to make the land
      productive, as long as it is carried out responsibly according to local fady
      (taboos). As well as facing problems of translating conservation goals into local
      values and misunderstanding the motives for forest clearance, policy has been
      based on a narrative that attaches particular land use practices to ethnic
      identities. I argue that this ignores the history and fluid reality of both
      identity and land use.

PMID- 22413175
TI  - Foucault, fields of governability, and the population-family-economy nexus in
      China.
AB  - It was only in the early twentieth century that China discovered that it had a
      population, at least if a population is understood not as a simple number of
      people but instead in terms of such features as variable levels of health, birth
      and death rates, age, sex, dependency ratios, and so on-as an object with a
      distinct rationality and intrinsic dynamics that can be made the target of a
      specific kind of direct intervention. In 1900, such a developmentalist conception
      of the population simply did not exist in China; by the 1930s, it pervaded the
      entire social and political field from top to bottom. Through a reading of a
      series of foundational texts in population and family reformism in China, this
      paper argues that this birth of the Chinese population occurred as a result of a
      general transformation of practices of governing, one that necessarily also
      involved a reconceptualization of the family and a new logic of overall social
      rationalization; in short, the isolation of a population-family-economy nexus as
      a central field of modern governing. This process is captured by elaborating and
      extending Foucault's studies of the historical emergence of apparatuses
      (dispositifs) into a notion of fields of governability. Finally, this paper
      argues that the one-child policy, launched in the late 1970s, should be
      understood not in isolation from the imposition of the "family-responsibility
      system" in agriculture and market reforms in exactly that period, but as part
      mutatis mutandis-of a return to a form of governing that was developed in the
      first half of the twentieth century.

PMID- 22413176
TI  - The incommensurability of psychoanalysis and history.
AB  - This article argues that, although psychoanalysis and history have different
      conceptions of time and causality, there can be a productive relationship between
      them. Psychoanalysis can force historians to question their certainty about
      facts, narrative, and cause; it introduces disturbing notions about unconscious
      motivation and the effects of fantasy on the making of history. This was not the
      case with the movement for psychohistory that began in the 1970s. Then the
      influence of American ego-psychology on history-writing promoted the idea of
      compatibility between the two disciplines in ways that undercut the critical
      possibilities of their interaction. The work of the French historian Michel de
      Certeau provides theoretical insight into the uses of incommensurability, while
      that of Lyndal Roper demonstrates both its limits and its value for enriching
      historical understanding.

PMID- 22413178
TI  - [Editorial note. Physicians and writers].

PMID- 22413177
TI  - Three thousand families: English Canada's colonizing vision and British family
      settlement, 1919-39.
AB  - After the First World War, Canada's immigration policy became more restrictive
      and immigration more controlled. For English Canadians, immigration of the "right
      type" of people-those from the British Isles-remained vital to strengthening the
      nation. This article examines the 3,000 Family Scheme, a joint British-Canadian
      settlement project in which British families, comprised of over 18,000
      individuals, were relocated to homesteads as colonizers of Canada's remote areas.
      There, many endured isolation and hardship, and were largely blamed for their own
      plight. A nation-building project that failed, the 3,000 Family Scheme reveals
      the connections among several enduring national myths in the interwar years: the
      potential for agricultural expansion, British superiority, and the capabilities
      of a maturing Canadian state to control the settlement process.

PMID- 22413179
TI  - Understanding cardiovascular disease across the lifespan. Abstracts of the 26th
      Annual International Interdisciplinary Conference on Hypertension and Related
      Risk Factors in Ethnic Populations. July 8-10, 2011. Boston, Massachusetts, USA.

PMID- 22413180
TI  - Veterinary medicine in the global community.

PMID- 22413181
TI  - Concern regarding  application of exclusion  criteria in PPA study.

PMID- 22413182
TI  - Bats increasingly seen as vectors.

PMID- 22413183
TI  - NIH suspends new chimp  research grants.

PMID- 22413184
TI  - Seal disease investigation intensifies.

PMID- 22413185
TI  - FDA cancels 1977 drug withdrawal bids.

PMID- 22413186
TI  - Cephalosporin use  restricted in livestock.

PMID- 22413187
TI  - Healthcare facilities.

PMID- 22413188
TI  - Healthcare workforce.

PMID- 22413189
TI  - Healthcare information technology.

PMID- 22413190
TI  - Medical malpractice and tort reform.

PMID- 22413191
TI  - Quality of healthcare.

PMID- 22413192
TI  - Immobilization and translocation of the white (square-lipped) rhinoceros.

PMID- 22413193
TI  - Restraint of undomesticated animals.
AB  - The capture, by means of chemical immobilization, of about 100 large African
      animals of 17 different species was accomplished by use of compound M.99, an
      oripavine with morphine-like activity, but with approximately 1,000 times the
      activity of morphine. Usually, the compound was used in conjunction with a
      tranquilizer and scopolamine. The small dose required enabled M.99 to be
      administered by a projectile syringe of 2-ml. capacity. The effect of the
      immobilizing compound can be reversed with nalorphine or with compound M.285.

PMID- 22413194
TI  - Isolation of Edwardsiella tarda from a sea lion and two alligators.
AB  - Edwardsiella tarda was isolated from a sea lion and 2 alligators on 3 separate
      occasions. The 3 isolates were not serologically identical. Specific pathologic
      effects of E. tarda could not be determined.

PMID- 22413195
TI  - Relationship of dietary histamine to gastric ulcers in the dolphin.
AB  - Gastric ulcers and erosions were found in a captive bottle-nosed dolphin. The
      results of gross and histologic examination suggested peptic digestion as the
      cause of ulcerations in the 1st compartment. The underlying cause of the erosions
      in the 2nd compartment appeared to be based on vascular rather than peptic
      mechanisms. Among the many factors responsible for these lesions, histamine,
      found in inadequately preserved dietary fish, was implicated as the initial
      ulcerogenic stimulant.

PMID- 22413196
TI  - Clinical jaundice in a dolphin.
AB  - Clinical icterus related to hepatic fibrosis and atrophy, pancreatic fibrosis,
      and fibrosis of the extrahepatic biliary system was observed in a mature male
      bottle-nosed dolphin. The underlying cause of the hepatic disease was
      undetermined.

PMID- 22413197
TI  - Use of droperidol and fentanyl for analgesia and sedation in primates.
AB  - A combination of droperidol and fentanyl produces qualitatively similar
      pharmacologic effects in dogs and primates. Unlike the dog, however, primates did
      not appear to respond to auditory stimuli. As a result of the analgesic and
      sedative or tranquil state produced in primates, the animals were easily handled
      and tolerant of painful stimuli. The principal desirable features of the
      combination were high analgesic and sedative potency and a rapid onset of action
      following intramuscular administration. High doses produced respiratory
      depression. However, this effect was easily reversed by administering nalorphine
      hydrochloride.

PMID- 22413198
TI  - Echinococcosis in a drill baboon.

PMID- 22413199
TI  - Hepatocystis kochi in Cercopithecus monkeys.

PMID- 22413200
TI  - Air transport of monkeys from India.

PMID- 22413201
TI  - Hypervitaminosis D in green iguanas.
AB  - Two green iguanas, with a dietary supplement of vitamin D, calcium, and
      phosphorus, had gross and microscopic lesions of hypervitaminosis D characterized
      by massive deposition of calcium salts in the media of elastic arteries and
      terminal nephritis. Hypervitaminosis is a malady that should be kept in mind in
      dealing with captive wild animals, especially when exact nutritional requirements
      are not known.

PMID- 22413202
TI  - Vascular lesions of Dirofilaria immitis in the red fox.
AB  - Dirofilaria immitis was found in the right ventricle, pulmonary artery, and lungs
      of 2 red foxes (Vulpes fulva) in Connecticut. The most significant lesions
      occurred in the pulmonary artery and consisted of focal atheromatous-like intimal
      plaques, diffuse subintimal accumulations of inflammatory cells, and marked
      villose endarteritis in the elastic portion of the pulmonary artery. Medial
      hyperplasia of the muscular branches, along with periarteritis, was found in 1
      fox. These 2 cases may be a further indication of the increased incidence of this
      disease in Carnivora in the State of Connecticut.

PMID- 22413203
TI  - Aleutian disease in the ferret.
AB  - Ferrets inoculated with Aleutian disease (AD)-infective material of mink origin
      harbored the infective agent for at least 136 days after inoculation. In
      contrast, hamsters given a similar inoculum of infective material no longer
      harbored the infective agent at 21 days postinoculation. During the infective
      period, neither ferrets nor hamsters had any detectable illness. However, in
      certain ferrets, massive periportal lymphocytic infiltrates were observed. A
      survey of ferrets from different ranches revealed similar lymphocytic infiltrates
      only in ferrets raised on a ranch which had AD-infected mink.

PMID- 22413204
TI  - Mastitis in mink due to Staphylococcus aureus and Escherichia coli.
AB  - An epizootic of mastitis in mink due to Staphylococcus aureus and Escherichia
      coli associated with food poisoning was studied on a Connecticut ranch with 3,500
      mink. In the course of the epizootic, approximately 2,000 mink kits and 480 adult
      mink, mostly nursing females, died within 10 days. Affected females had swollen
      mammary glands due to acute mastitis; S. aureus was isolated in pure culture from
      2 mink and E. coli in pure culture from a 3rd. Staphylococcus aureus was isolated
      from the organs of 1 mink kit, S. aureus and E. coli from a 2nd kit, and E. coli
      from a 3rd. The organs of the remaining 7 kits examined did not contain bacteria.
      Both isolates were pathogenic when inoculated intraperitoneally into mice and
      mink, causing fatal septicemia within 16 to 24 hours. The meat from a septicemic
      bovine carcass fed prior to the epizootic was considered a possible source of
      infection, since it was found to be heavily contaminated with E. coli, S. aureus,
      and Streptococcus spp.

PMID- 22413205
TI  - Control of some internal parasites of chinchillas.
AB  - An unidentified coccidia was found in chinchillas. Treatment with sulfamethazine
      apparently eradicated the infection from several herds. Ostertagia females and 1
      Trichostrongylus colubriformis male were also found in chinchillas, causing
      emaciation. A dose of thiabendazole of 100 mg./kg. of body weight was effective
      against the roundworms, but it was toxic. A dose of trichlorphon, 100 mg./kg. of
      body weight, was effective and safe. Hymenolepis infection caused emaciation and
      death. Treatment with doses of niclosamide, 200 mg./kg. of body weight, was
      successful in removing tapeworms, ending deaths, and improving the condition of
      the host. It did not eradicate the infection.

PMID- 22413206
TI  - Herniation of the seminal vesicles into the scrotum of the guinea pig.

PMID- 22413207
TI  - The use of combined inhalation anesthesia in laboratory animal surgery.
AB  - General anesthesia was induced successfully in 250 laboratory rats by use of a
      gas machine, human infant-type mask, and combinations of oxygen, nitrous oxide,
      helium, carbon dioxide, and ether. Ease and speed of induction and recovery and a
      relatively wide margin of safety were offered by use of the gas machine.

PMID- 22413208
TI  - Emesis in birds.
AB  - Comparative studies of emesis in the herring gull, pigeon, chicken, and cowbird
      were conducted, using orally administered copper sulfate and intravenously
      administered copper sulfate, hydergine, apomorphine, and lanatoside C. A response
      to every emetic was elicited from some birds. However, the individual and species
      differences among the birds were as great as those among mammals. Further, the
      response of the avian species studied did not indicate that any of them could be
      used to predict how a specific mammal would react. The differences in response to
      the emetics by the birds do not offer any simple pattern related to feeding
      behavior.

PMID- 22413209
TI  - Disseminated aspergillosis in a mynah bird.
AB  - Chronic nodular disseminated aspergillosis caused the death of a 9-month-old
      mynah bird (Gracula religiosa intermedia). The disease was diagnosed at
      postmortem examination, although it was suspected in the terminal state. It was
      unresponsive to various antibiotics and sulfonamides. Clinical signs consisted of
      feather ruffling, anorexia, weight loss, episodes of diarrhea, and finally
      orthopnea, dyspnea, and severe lethargy. Terminally there was right hemiparesis
      involving the right upper lid and right leg. Principal pathologic findings
      consisted of yellow-whitish nodules involving the lungs, granulomatous
      dissemination to the liver and kidneys, transgression of the inflammatory
      process, with formation of subcutaneous nodules in the pectoral muscles, and
      destruction of the ribs. The granulomatous process was characterized by marked
      chronic fibrous reaction.

PMID- 22413210
TI  - Chlordiazepoxide and pentobarbital as tranquilizers for cowbirds and coturnix
      quail.
AB  - The effects of ad libitum ingestion of chlordiazepoxide and sodium pentobarbital
      on penned cowbirds and coturnix quail were compared. The agents were incorporated
      into feed and offered to individually marked birds. Individual response to each
      agent appeared to relate more to the quantity of food ingested than to the
      percentage by weight of agent in the food. Response of both species to
      chlordiazepoxide was similar at the 15% dose despite weight differences of the
      birds. Responses were too variable to demonstrate significant differences when
      sodium pentobarbital at the 10% dose was given to both species. No deaths
      occurred among birds given chlordiazepoxide, whereas 4 quail and 1 cowbird died
      from sodium pentobarbital ingestion.

PMID- 22413211
TI  - High-altitude canine oxygen mask.

PMID- 22413212
TI  - Wildlife disease--a growing specialty.

PMID- 22413213
TI  - What is your diagnosis? Severe pulmonary infiltration due to pneumonia.

PMID- 22413214
TI  - A special issue on nanotechnology in China.

PMID- 22413215
TI  - The research progress of quantum dot lasers and photodetectors in China.
AB  - Self-assembled In(Ga)As/GaAs quantum dots (QDs), known as "artificial atoms" for
      their fully quantized electronic states, show unique physical properties and new
      prospects for applications. Based on the QDs, an increasing number of leading
      laboratories on the world engage in developing novel optoelectronic devices with
      special advantages over existing devices. This paper reviews the current research
      developments in self-assembled QD devices in China, covering QD lasers and inter
      sub-level QD photodetectors. QD devices in China are undergoing a rapid advance
      and have achieved the world's best results in terms of certain characteristics.

PMID- 22413216
TI  - Multiphonon resonant Raman scattering (MRRS) of semiconductor nanomaterials for
      biodetection.
AB  - Robust, rapid and sensitive detection of specific molecules at ultra low
      concentrations is becoming increasing important, especially for medical
      diagnosis, food safety and environmental protection. Various spectroscopic
      techniques have been developed to apply in analysis and assay fields, including
      fluorescent spectroscopy, infrared spectroscopy and surface-enhanced Raman
      spectroscopy (SERS), etc. Multiphonon resonant Raman scattering (MRRS) technique
      is usually used to investigate optical lattice vibrations and the interaction
      between phonon and electron in semiconductor nanomaterials. Recently, it exhibits
      fascinating prospects in biodetection due to its significant specific
      spectroscopic and material advantages. The multiple-order phonon lines are
      material intrinsic and thus can be used as a characteristic fingerprint signal to
      label the biomolecules. The strong anti-interference capacity to external
      environment allows an accurate detection. Narrow bandwidth makes the technique
      suitable for multiplexed analysis. Proper choice of nontoxic inorganic
      semiconductor materials facilitates in-vivo detection. This review focuses on the
      current theoretical and technical developments in MRRS of semiconductor
      nanomaterials and highlights their applications in bioanalysis. The basic
      principle, merits, challenges and future perspectives of MRRS detection technique
      are discussed.

PMID- 22413217
TI  - Conduction and valence band discontinuities in some new semiconductor
      heterojunctions.
AB  - Conduction and valence band discontinuities (band offsets) in the heterojunctions
      consisting of ZnO/4H-SiC, ZnO/GaAs, MgO/4H-SiC, MgO/AIN, InN/ZnO, InN/GaAs,
      MgO/InN, and InN/4H-SiC, were precisely determined by X-ray photoelectron
      spectroscopy (XPS) measurement. As an example, the XPS measurement on the ZnO/4H
      SiC heterojunction is described in detail in the beginning of the section of the
      experiments. We also analyzed several factors which may have impact on the band
      offset in a practical heterojunction. The deviation in band offset induced by
      both polar and non-polar heterojunction band bending from the true value was also
      characterized by taking into account the intrinsic polarization field in the
      heterojunction consisting of the two polar materials.

PMID- 22413218
TI  - Recent developments of hybrid nanocrystal/polymer bulk heterojunction solar
      cells.
AB  - Hybrid nanocrystal/polymer bulk heterojunction (BHJ) solar cells consisting of
      colloidal inorganic semiconductor nanocrystals as electron acceptors and
      conjugated polymers as electron donors have been extensively investigated in the
      past few decades, which take advantage of the strongpoints of the inorganic
      semiconductor nanocrystals and the conjugated polymers. Currently, power
      conversion efficiency over 3% for the hybrid nanocrystal/polymer BHJ solar cells
      has been achieved. Although the development of hybrid nanocrystal/polymer BHJ
      solar cells lacks behind the international level, great progress in this research
      field has been made in China. In this article, we first review the general
      fabrication techniques and general working principles of hybrid
      nanocrystal/polymer BHJ solar cells. Secondly, we highlight the international and
      national developments of hybrid nanocrystal/polymer BHJ solar cells based on
      different types of semiconductor nanocrystals and conjugated polymers. Finally,
      we give a future outlook for the hybrid nanocrystal/polymer BHJ solar cells in
      the worldwide.

PMID- 22413219
TI  - Controllable synthesis and biomedical applications of silver nanomaterials.
AB  - Silver nanomaterials have lots of peculiar and exciting physical and chemical
      properties that are different from massive silver, so the synthesis and
      applications of silver nanomaterials have attracted a great deal of attention in
      the last decade. Currently, all kinds of silver nanomaterials having different
      shapes and sizes have been synthesized by many ingenious methods, and silver
      nanomaterials have exhibited extensive application prospects in many fields
      especially in biomedical aspect. In this article, the controllable synthesis of
      silver nanomaterials including nanorods, nanowires, nanotubes, nanoprisms,
      nanoplates, nanodisks, nanospheres, and nanopolyhedrons, etc. are reviewed.
      Silver nanomaterials are most utilized in the form of nanoparticles, so the main
      biomedical applications of silver nanoparticles, such as antibacterial and
      antiviral applications, antitumor applications, biosensors and biological labels,
      optical imaging and imaging intensifier, are discussed. Although antibacterial
      applications are still the most important aspects of silver nanomaterials at
      present, antitumor, optical sensors and imaging applications of silver
      nanomaterials have also shown good potential perspectives. More biomedical
      applications of silver nanomaterials still need to be exploited for the future,
      and the biological safety of silver nanomaterials also should be paid enough
      attention before their practical applications.

PMID- 22413220
TI  - Gain characteristics of LaF3:Er, Yb nanoparticle-doped waveguide amplifier.
AB  - Fundamental rate equations and power propagation equations were used to simulate
      the gain factors of LaF3:Er, Yb nanoparticle-doped waveguide amplifiers excited
      at 980 nm. The gain first increased and then remained nearly constant with pump
      power increasing. The gain and the threshold pump power increased with increasing
      concentration of Er3+. The calculated gain of the concentration 0.75 x 10(26)
      ions/m3 on a 4 cm long waveguide was 3.6 dB. An optimum waveguide length was
      found for the highest gain and it was getting larger with the increase of the
      pump power. When the lifetime decreases from the Judd-Ofelt calculated value of
      13.34 ms to the measured value of 60 micros, the required pump power of a 0.5 dB
      gain increased one level. We obtained a longer 4I(13/2) lifetime (100 micros)
      through decreasing the proportions of Er3+ and Yb3+ in nanoparticles and found
      that the threshold pump power decreased more at the expenses of saturated gain.

PMID- 22413221
TI  - Visible luminescence mechanism of ZnO nanoparticles synthesized by sol-gel
      method.
AB  - We presented our investigations on the absorption and emission properties of the
      nanocrystalline ZnO particles of different particle sizes (2 nm-5 nm) by sol-gel
      method. In the room temperature PL spectra, three emission bands, ultraviolet
      (UV), blue and green were observed. With increasing the particle sizes, both the
      UV and the visible emission bands shifted to lower energies progressively. From
      the size-dependency, there was a linear relationship between the energetic maxima
      of the UV and the green emission bands with a slope of about 0.26, which
      indicated that the green luminescence of ZnO was produced by the transitions of
      electrons from deep level to the valence band (or shallow acceptor level). A
      linear dependence was also found between the energetic maxima of the UV and the
      blue emissions with a slope of 0.15, the origin this blue emission band is not
      clear at present. While in van Dijken et al.'s paper, however, they identified
      only two emission bands in the emission spectra, an UV and a broad visible
      emission band, and the linear fit between the energetic maxima of these two bands
      in particles of different sizes has a slope of 0.6, so they proposed that the
      visible emission in ZnO was originated from the recombination of a shallowly
      trapped electron with a deeply trapped hole. We attributed this divergence to the
      fact that the broad visible band is actually composed of two separate emission
      bands originated from two different recombination processes, and should not had
      been treated as one emission band.

PMID- 22413222
TI  - [6,6]-phenyl C61, butyric acid methyl ester-polymer nanocomposite: a good
      material platform for organic light-emitting diodes.
AB  - PCBM-polymer nanocomposites [[6,6]-Phenyl C61 butyric acid methyl ester
      (PCBM):Poly(9-vinylcarbazole) (PVK)] were prepared by dissolving them in
      chloroform. Photophysical properties were studied first, and then the hole-only
      devices were fabricated to study the hole-transporting properties. The specially
      designed organic light-emitting diodes (OLEDs) with the structure of indium tin
      oxide (ITO)/PCBM:PVK (x wt%, approximately 40 nm)/4,4'-bis(2,2'-diphenylvinyl)
      1,1'-biphenyl (DPVBi) (30 nm)/Tris-(8-hydroxyquinoline)aluminum (Alq3) (30
      nm)/lithium fluoride (LiF) (1 nm)/Al were fabricated to verify the transport
      properties of the nanocomposites. Finally, the nanocomposites were applied in the
      Alq3-based OLEDs as a hole-transporting layer. A significant improvement was
      observed in OLEDs when the nanocomposites were used to replace the conventional
      pristine PVK.

PMID- 22413223
TI  - Electroluminescence of zinc selenium (ZnSe) nanocrystals co-doped with poly[2
      methoxy-5-(2'-ethylhexyloxy-p-phenylenevinylene)] (MEH-PPV).
AB  - We have synthesized water soluble zinc selenium (ZnSe) nanocrystals by using
      mercaotoacetic acid (TGA) as the stabilizer. The synthesized ZnSe nanocrystals
      were co-doped with poly[2-methoxy-5-(2'-ethylhexyloxy-p-phenylenevinylene)] (MEH
      PPV) to fabricate an organic/ inorganic hybrid multilayer light-emitting device
      (LED). The structure of the device was indium-tin-oxide (ITO)/poly (ethylene
      dioxythiophene):poly(styrenesul-fonate) (PEDOT:PSS)/MEH-PPV:ZnSe/bathocuproine
      (BCP)/tris-(8-hydroxylquinoline)-aluminum (Alq3)/Al. We demonstrate that the
      device has a lower driving voltage and increased current densities and power
      efficiencies owing to the co-doped ZnSe quantum dots. We obtained good efficiency
      of the devices when the quality ratio of MEH-PPV and ZnSe quantum dots was 1:1.

PMID- 22413224
TI  - Organic photovoltaic devices based on an acceptor of solution-processable
      functionalized graphene.
AB  - We prepared the exfoliation of graphite, which was necessary for the production
      of graphene sheets that are desirable for the fabrication of nano-composites.
      Then a Solution-Processable Functionalized Graphene (SPFGraphene) with
      functionalization groups doped with P3HT hybrid thin film-based organic
      photovoltaic cells (OPVCs) was systematically identified using a general device
      structure of, ITO/PEDOT:PSS/P3HT:SPFGraphene/LiF/Al. The effect of annealing on
      the photoelectric properties of the SPFGraphene was analyzed by Fourier transform
      infrared FT-IR spectroscopy and solar cell performance. After treatment at
      different annealing temperatures, with an increase in the SPFGraphene content,
      the short-circuit current density J(SC) and power conversion efficiency PCE of
      the hybrid devices increased first, reaching the peak efficiency for the 10 wt%
      SPFGraphene content, and then decreased. After annealing at 160 degrees C, the
      device containing 10 wt% SPFGraphene showed the open-circuit voltage V(OC) of
      0.73 V, the J(SC) value of 3.98 mA cm(-2), fill factor (FF) value of 0.36, the
      PCE value of 1.046%. After thermal annealing at 210 degrees C, with the removal
      of the functional groups and recovery of the pi-conjugated areas, the
      conductivity of the graphene sheet and the charge carrier-transport mobility
      increased greatly, the J(SC) value of the 10 wt% SPFGraphene content device
      increased to 4.2 mA cm(-2), the V(OC) value decreased to 0.59 V, which may be
      attributed to the altered work-function value of the functionalized graphene and
      low quasi-Fermi levels for electrons and holes, the FF value was 0.27, and the
      PCE was 0.669%, which is lower than the former one. The results indicated that
      annealing at the appropriate temperature can improve the device performance
      greatly, and the functionalized graphene is expected to be a competitive
      candidate in organic photovoltaic applications because it is soluble, cheap,
      easily prepared, stable, and inert against the ambient conditions.

PMID- 22413225
TI  - Synthesis and luminescence properties of Sr2SiO4: Eu3+, Dy3+ phosphors by the sol
      gel method.
AB  - The Sr2SiO4:Eu3+, Dy3+ phosphors for white light emitting diodes (LEDs) were
      synthesized by the sol-gel method. The microstructure and luminescent properties
      of the obtained Sr2SiO4:Eu3+, Dy3+ particles were well characterized. The results
      demonstrate that the Sr2SiO4:Eu3+, Dy3+ particles, which have spherical
      morphology, emitted an intensive white light emission under excitation at 386 nm.
      The phosphors show three emission peaks: the blue emission at 486 nm
      corresponding to the 4F(9/2)-6H(15/2) transition of Dy3+, the yellow emission at
      575 nm corresponding to the 4F(9/2)-6H(13/2) transition of Dy3+, and the red
      emission at 615 nm corresponding to the 5D0-7F2 transition of Eu3+. At the same
      time, the effect of Eu3+ concentration on the emission intensities of
      Sr2SiO4:Eu3+, Dy3+ was investigated in detail. The phosphors used for white LEDs
      were obtained by combining near ultraviolet (NUV) light (386 nm) with
      Sr2SiO4:0.04Dy3+, 0.01Eu3+ phosphors with the characteristic of Commission
      Internationale de l'Eclairage (CIE) chromaticity coordinate (x, y) of (0.33,
      0.34), and color temperature Tc of 5,603 K. In addition, the effect of the charge
      compensators (Li+, Na+, and K+ ions) on the photoluminescence (PL) emission
      intensities were studied.

PMID- 22413226
TI  - Optical spectroscopy of Eu3+ ions in tetragonal ZrO2 nanocrystals.
AB  - A facile solvothermal method was introduced to incorporate Eu3+ ions into the
      monodisperse tetragonal ZrO2 nanocrystals (NCs) with small size of approximately
      4 nm. The optical properties for Eu3+ doped ZrO2 NCs were investigated in detail
      by using the photoluminescence (PL) spectroscopy at room and low temperatures.
      Intense red emissions from Eu3+ ions could be achieved via the host
      sensitization, which was found to be much more efficient than the direct
      excitation of lanthanide ions. Moreover, multiple sites of Eu3+ as well as the
      host-to-Eu3+ energy transfer were also revealed based on the PL analyses.

PMID- 22413227
TI  - Characteristics of organic light emitting diodes with vanadium oxide solution
      treated indium tin oxide.
AB  - The effect of indium tin oxide (ITO) in organic light emitting diodes (OLEDs)
      treated by vanadium penoxide (V2O5) saturation solution was studied. The device
      with ITO treated by ultraviolet-ozone (UV-ozone) was fabricated in the same run
      for comparison. It was found that the V2O5 solution-treated devices have much
      higher current efficiency compared to the device with bare ITO and UV-ozone
      treated ITO as the anode. The turn-on voltages were reduced by around 2.5 V, and
      the luminances were about 1.69 times greater than that of the conventional device
      at 16 V driving voltage. Series resistances were determined by the slope of the
      current-voltage curve and the ac impedance spectroscopy technique.

PMID- 22413228
TI  - Graphene layers from reduction of exfoliated graphite oxide.
AB  - Graphene oxide (GO) of approximately 1 nm was generated from exfoliated graphitic
      oxide using a modified Hummers method through ultrasonic treatment in water, and
      the GO film was reduced under protection of Ar/H2 flow at 800 degrees C.
      Moreover, the obtained graphene film has a high conductivity of 383 S/cm at 10-20
      nm thickness.

PMID- 22413229
TI  - Luminescent properties of ZnS:Mn2+/ZnS core/shell nanocrystals.
AB  - High-quality ZnS:Mn2+/ZnS core/shell nanocrystals (NCs) with a core crystal
      diameter of 6.1 nm and 1.15 nm thick shells were synthesized via a high-boiling
      solvent process. The energy levels of the conduction band and valance band are
      estimated to be -3.2 eV and -6.8 eV by cyclic voltammetry and ultraviolet-visible
      (UV-vis) absorption spectra. The ZnS:Mn2+/ZnS NC emission peak is primarily
      located at 580 nm under 310 nm light excitation, originating from the charge
      transition from 4T1 to 6A1 within the 3d5 configuration of the Mn2+ ion. Based on
      ZnS:Mn2+/ZnS NCs as the active layer electroluminescent devices, the emission
      peak mainly locates at 460 nm with one shoulder emission peaking at 580 nm. The
      photoluminescence and electroluminescence properties of ZnS:Mn2+/ZnS NCs are
      investigated in the view of charge carrier injection and energy level alignment.

PMID- 22413230
TI  - Improving photovoltaic properties by incorporating solution-processable
      functionalized graphene into poly(3-octylthiophene)/phenyl c61 butyric acid
      methyl ester photovoltaic devices.
AB  - We report the optoelectronic properties occurring in solution-processable
      functionalized graphene (SPFGraphene)-PCBM/poly(3-octylthiophene) (P3OT)
      composites. The structural configuration of the devices is
      ITO/PEDOT:PSS/P3OT:PCBM-SPFGraphene/LiF/Al. The best results were obtained with a
      P3OT/PCBM (1:1) mixture with 8 wt% of SPFGraphene in an open-circuit voltage
      (V(OC)) of 0.65 V, a short-circuit current density (J(SC)) of 4.2 mA/cm2, and a
      fill factor (FF) of 0.35, which led to a power conversion efficiency of 0.95% at
      illumination at 100 mW/cm2 AM 1.5. In the P3OT:PCBM-SPFGraphene composite, the
      SPFGraphene acted as exciton dissociation sites and provided the transport
      pathway of the lowest unoccupied molecular orbital (LUMO)-graphene-Al. Doping SPF
      Graphene into P3OT resulted in appropriate energetic distance between the highest
      occupied molecular orbital (HOMO) and LUMO of the donor/acceptor for a high open
      circuit voltage and provided higher exciton dissociation volume mobility of
      carrier transport for a large short-circuit current density.

PMID- 22413231
TI  - Metal ion detection with oligo(ethylene glycol) monolayer-modified gold
      nanoparticles.
AB  - Two colorimetric sensors of gold nanoparticles (AuNPs) modified with different
      oligo(ethylene glycol)-containing organic molecules have been developed to detect
      metal ions by ultraviolet-visible (UV-vis) extinction spectroscopy. These sensors
      display different responses to some metal ions. One exhibits high selectivity for
      Hg2+ over a variety of competitive metal ions and the other one can respond to a
      multitude of metal ions. These differences might result from the different
      functionalized end groups of the modified molecules. Coordination effect, pH
      response, and ionic strength were investigated to understand the mechanism of the
      responses to metal ions. The results suggested that the colorimetric responses
      were mainly induced by the coordination effect of the modified organic molecules
      and the removing of the modified organic molecules caused by metal ions.

PMID- 22413232
TI  - One-step synthesis and optical properties of water-soluble and amine
      functionalized Dy3+-doped BaFCl nanocrystals.
AB  - Water-soluble and amino-functionalized luminescent Dy3+-doped BaFCl nanocrystals
      have been synthesized for the first time via a facile one-step modified
      solvothermal method with polyethyleneimine (PEI) as capping agent. The obtained
      BaFCl:Dy3+ nanocrystals have a size of about 40 nm, remain stable in aqueous
      solutions under different pH, and exhibit intense visible luminescence of Dy3+.
      The synthesized nanocrystals featuring long-lived luminescence may have potential
      applications as time-resolved photoluminescent probes for bio-applications.

PMID- 22413233
TI  - Broadband downconversion in Bi3+, Yb3+-Co-doped YVO4 phosphor.
AB  - Yttrium vanadate phosphors co-doped with Bi3+ and Yb3+ ions have been prepared
      via the solid-state reaction. The phosphors were characterized by various methods
      including X-ray diffraction, photoluminescence excitation and photoluminescence
      spectra. Upon ultraviolet (UV) light excitation, an intense near-infrared (NIR)
      emission of Yb3+ corresponding to the transition of 2F(5/2) --> 2F(7/2) peaking
      at 985 nm was observed as a result of energy transfer from O2(-)-V5+ or Bi3+-V5+
      charge transfer state (CTS) to Yb3+. A broad excitation band ranging from 250 to
      375 nm was recorded when the Yb3+ emission was monitored, which suggests an
      efficient energy transfer from CTS to Yb3+ ions. The dependence of Yb3+ doping
      concentration on the visible emission, the NIR emission and decay lifetime has
      been investigated. The results of visible and NIR spectral evolution with
      temperature indicate that the mechanism for the NIR-emission is mainly phonon
      assisted energy transfer at room temperature, while the mechanism is mainly
      cooperative energy transfer at low temperature. The YVO4:Bi3+, Yb3+ phosphor has
      prospects for realizing high efficiency crystalline Si solar cells by converting
      broadband UV energy into NIR light.

PMID- 22413234
TI  - Near infrared quantum cutting in Yb3+-doped NaY(WO4)2 phosphor with a high
      quenching concentration.
AB  - The near infrared quantum cutting phenomenon has been demonstrated in Yb3+-doped
      NaY(WO4)2 phosphor. The phosphor shows intense absorptions in the range of 250
      330 nm, and intense near infrared emission is obtained via cooperative energy
      transfer from the host to Yb3+, which involves the emission of two near infrared
      photons around 1000 nm from an absorbed ultraviolet photon. Decay curves of the
      host emission around 480 nm have been measured, and the calculated energy
      transfer efficiency turns out to be as high as 81.6% at 40 mol% Yb3+ doping.
      Besides, infrared emission intensities increase with increasing Yb3+
      concentration until the doping gets larger than 40 mol%. The excellent
      luminescence properties of the Yb3+-doped NaY(WO4)2 phosphor demonstrate its
      potential application as a better quantum cutting layer to enhance the energy
      efficiency of solar cells.

PMID- 22413235
TI  - Enhanced ultraviolet upconversion luminescence of Tm and Yb codoped ZrF4-BaF2
      LaF3-AlF3-NaF glass.
AB  - Ultraviolet (UV) upconversion (UC) luminescence properties of Tm3+ ions
      sensitized by Yb3+ ions in ZrF4-BaF2-LaF3-AlF3-NaF (ZBLAN) glass were studied in
      detail. Under the excitation from a 980 nm continuous wave (CW) diode laser, red,
      blue, and even UV emissions were observed in the fluorozirconate glass. Several
      fluorescence bands appeared in the UC emission spectrum from 292.8 nm to 805.8
      nm. The UC emission peaks at 291 nm, 347 nm, 363 nm, 454 nm, 475 nm, 647 nm, 687
      nm, and 804 nm correspond to the transitions of 1I6 --> 3H6, 1I6 --> 3F4, 1D2 -->
      3H6, 1D2 --> 3F4, 1G4 --> 3H6, 1G4 --> 3F4, 3F3 --> 3H6, and 3H4 --> 3H6,
      respectively. Experimental results of intensity dependence of the up-converted
      fluorescence on the pump power indicate a five-photon excitation scheme of 1I6
      energy level.

PMID- 22413236
TI  - Enhanced red upconversion luminescence in Er-Tm codoped NaYF4 phosphor.
AB  - This paper presents a study on the enhanced red upconversion (UC) luminescence
      via efficient energy transfer (ET) between Er3+ and Tm3+ in Er-Tm codoped NaYF4
      microtubes. Er doped and Er-Tm codoped NaYF4 UC hollow microtubes have been
      synthesized using a hydrothermal method. Under 1560 nm excitation from a diode
      laser, the Er doped NaYF4 microtubes emitted dominant green UC luminescence while
      the Er-Tm codoped NaYF4 microtubes emitted dominant red UC luminescence, which
      implies the energy transfer between Er3+ and Tm3+ plays a key role in the
      enhanced red UC emissions. The red UC luminescence is significantly enhanced
      compared with the green UC luminescence with the increase of Tm3+ doping
      concentration. In addition, our experimental results show that the UC
      luminescence properties under 980 nm excitation are almost identical with that
      under 1560 nm excitation. Furthermore, the possible ET mechanism was proposed on
      the basis of our experimental results.

PMID- 22413237
TI  - One-step synthesis and enhanced luminescence of Eu-doped BaF2 nanocubes.
AB  - Europium (Eu3+) doped BaF2 nanocubes were synthesized successfully by a simple
      method, using oleic acid (OA) as a capping agent. The structure properties were
      characterized by XRD, FE-SEM, and FTIR. FE-SEM analysis indicates that the
      prepared nanomaterials have nanocubic morphology with a side length about 150 nm
      and can be controlled well by adjusting OA concentration. Moreover, the
      photoluminescence spectra of the samples were investigated. The emission
      intensity of the BaF2:Eu3+ nanocubes have been enhanced greatly after modified
      with proper amount of OA, which is promising for new applications and optical
      devices.

PMID- 22413238
TI  - Metastable monoclinic ZnMoO4: hydrothermal synthesis, optical properties and
      photocatalytic performance.
AB  - Metastable monoclinic ZnMoO4 was successfully synthesized via a hydrothermal
      route with variation of reaction temperatures and time at pH value of 5.7.
      Systematic sample characterizations were carried out, including X-ray powder
      diffraction, scanning electron microscopy, Fourier transformed infrared spectra,
      UV-visible diffuse reflectance spectra, and photoluminescence spectra. The
      results show that all as-prepared ZnMoO4 samples were demonstrated to crystallize
      in a pure-phase of monoclinic wolframite structure. All samples were formed in
      plate-like morphology. Six IR active vibrational bands were observed in the wave
      number range of 400-900 cm(-1). The band gap of as-prepared ZnMoO4 was estimated
      to be 2.86 eV by Tauc equation. Photoluminescence measurement indicates that as
      prepared ZnMoO4 exhibits a broad blue-green emission under excitation wavelength
      of 280 nm at room temperature. Photocatalytic activity of as-prepared ZnMoO4 was
      examined by monitoring the degradation of methyl orange dye in an aqueous
      solution under UV radiation of 365 nm. The as-prepared ZnMoO4 obtained at 180
      degrees C for 40 h showed the best photocatalytic activity with completing
      degradation of MO in irradiation time of 120 min. Consequently, monoclinic ZnMoO4
      proved to be an efficient near visible light photocatalyst.

PMID- 22413239
TI  - Photocatalytic degradation and toxic effects of Ag-doped ZnO nanocrystallites.
AB  - Ag-doped ZnO nanocrystallites were synthesized from the precursor of Ag-doped
      zinc nitrate hexahydrate by applying hybrid induction and laser heating (HILH)
      techniques. The physical properties of prepared nanocrystallites were
      characterized by X-ray diffraction (XRD) and atomic force microscopy (AFM).
      Silver ions doping can greatly improve the photocatalytic efficiency of ZnO
      nanocrystallites. This was attributed to the change of surface properties of
      metal ions doped semiconductor, such as O vacancies, crystal deficiencies and
      increased specific surface area (SSA). Increasing the amount of silver ions
      resulted in increased lattice deficiency and hence enhanced the photocatalytic
      activity. UV-Vis methods were used to detect intermediates during the degradation
      of DBP. The results demonstrated that the degradation rate of DBP changed over
      time in line, this process was basically completed in 60 mins. The acute
      toxicities of several silver ions doped ZnO nanocrystallites were also
      investigated in this study by using Scenedesmus quadricauda.

PMID- 22413240
TI  - Evolution of luminescence properties of CdTe quantum dots in liquid/solid
      environment.
AB  - We studied the luminescence behavior of different sized CdTe quantum dots (QDs)
      dispersed in liquid solution, close-packed films and layer-by-layer assembled
      films respectively. The changes of emission color from CdTe QDs in water droplets
      during the evaporation of solvent have been observed. The quenching of the
      emission from small dots accompanied by the enhancement of the emission from
      large dots indicate that Forster resonance energy transfer processes occur from
      donors (small dots) to acceptors (large dot) for CdTe QDs system. Excitation
      (PLE) spectra confirm that the changes of the luminescence were attributed to the
      resonance energy transfer between small and larger dots in a mixed QD system.

PMID- 22413241
TI  - Surface-enhanced fluorescence of rhodamine 6G on the assembled silver
      nanostructures.
AB  - The fluorescence emission and enhancement of Rhodamine 6G on the silver island
      films (SiFs) with and without 4-Aminothiophenol molecules have been investigated.
      It was found that the SiFs without 4-Aminothiophenol molecules (PATP) have less
      contribution to the fluorescence enhancement. However, when PATP molecules as a
      spacer were deposited on the SiFs, obvious fluorescence enhanced effect was
      observed. The results show that the fluorescence enhancement depends on the
      morphology of the substrate surface and the distance between fluorophore
      molecules and the substrate surface. The experimental observations can be
      explained by local surface plasmon resonance and local field enhancement theory.

PMID- 22413242
TI  - Enhancement of gastric cell radiation sensitivity by chitosan-modified gold
      nanoparticles.
AB  - We explored the biocompatible gold nanoparticles (GNPs) with surface modified by
      chitosan in the applications of cell's response to X-ray irradiation. Substantial
      amounts of chitosan modified gold nanoparticles (CS-GNPs) were found to be
      internalized in cell cytoplasm revealed by transmission electron microscopy.
      Their in vitro cytotoxicity effects on MGC-803 cells and GES-1 cells were
      observed at 24, 48 and 72 h. The MTT results showed that CS-GNPs own excellent
      biocompatibility. The dose enhancement based on CS-GNPs induced the damage of MGC
      803 cells under X-ray irradiation, monitored by clonogenic cell survival assay.
      We also investigated their effects on the survival rates of MGC-803 cells during
      irradiation for a dose up to 10 Gy using a radio-oncology linear accelerator (6
      MeV). The survival fraction of cells incubated with different concentration of CS
      GNPs was obviously reduced in comparison with that irradiation alone. The result
      also revealed an increase of cell inhibition with increasing the concentration of
      CS-GNPs. In conclusion, CS-GNPs can enhance the cell radiation therapeutic
      sensitivity, and have potential application in tumor irradiation therapy in near
      future.

PMID- 22413243
TI  - Labeling primary nerve stem cells with quantum dots.
AB  - The primary nerve stem cells (NSCs) were labeled with the carboxyl QDs by passive
      loading. The studies on QDs' effect on the NSCs showed that with a proper
      concentration, QDs have little effect on NSCs growth and proliferation within a
      week, and the QDs did not affect either differentiation potential of NSCs or the
      protein expression of neuron and astrocyte derived from NSCs. The results
      suggested that this labeling method is appropriate for labeling studies in vitro.
      Combined with the unique optical properties of QDs, it is possibly to fulfill
      NSCs fate-tracking in vivo.

PMID- 22413244
TI  - CaMoO4:x%Yb3+: a novel near-infrared quantum-cutting phosphors via cooperative
      energy transfer.
AB  - An efficient near-infrared (NIR) dowmconversion (DC) has been demonstrated in the
      CaMoO4:Yb3+ phosphors. Very strong NIR emission around 998 nm from the 2F(7/2) -
      > 2F(5/2) transition of the Yb3+ has been observed under ultraviolet excitation.
      A similar broad excitation band due to the absorption of the host CaMoO4 has been
      recorded when the NIR emission of Yb3+ and the visible molybdate (MoO4(-2))
      emission are monitored, which suggests an efficient energy transfer (ET) from the
      host to the Yb3+. The Yb3+ concentration-dependent luminescence properties and
      lifetimes of both the visible and NIR emissions have also been studied. The
      lifetime of the molybdate emission decreases rapidly with the increasing Yb3+
      concentration, further verifying the efficient ET from the host to the Yb3+.
      Moreover, the low temperature measurements have also been carried out to
      investigate the ET mechanism in the phosphors. A cooperative energy transfer
      (CET) mechanism has been proposed to rationalize the DC effect. The newly studied
      CaMoO4:Yb3+ DC phosphors, which can convert the broadband emission of the MoO4(2
      ) into NIR emission of Yb3+ with a twofold increase in the photon number will
      have potential application in greatly enhancing the response of silicon-based
      solar cells with a relatively higher Yb3+ quenching concentration.

PMID- 22413245
TI  - Ab initio calculation of electronic structure and 4f-5d transition energies of
      Ce3+ doped in Y3Al5O12 nanocrystals.
AB  - The elementary-state electronic structure and 4f-5d transitions of Y3Al5O12:Ce3+
      nanocrystals simulated by several clusters were computed by the ab initio self
      consistent relativistic DV-X alpha (discrete variational X alpha) method. A 35
      ion cluster was chosen to simulate the local surroundings of Ce3+ doped in
      Y3Al5O12 bulk crystals while four additional smaller irregular clusters were also
      chosen to simulate the local surroundings of Ce3+ ions in nanocrystals. Besides
      obtaining the elementary-state 4f and 5d electronic structure, based on the
      transition-state calculations we also obtained the five 4f-5d transition energies
      for each of these clusters. We found that compared with the bulk crystals, for
      all the clusters simulating nanocrystals the first 4f-5d transition peak (the
      lowest energy peak) was blueshifted, and the second peak was redshifted a little,
      which are both in accordance with the observed experimental excitation spectra of
      5d luminescence of Y3Al5O12:Ce3+. We fitted the observed first two transition
      peaks in a published experimental excitation spectrum of nanocrystals by weighted
      summing of the excitation spectra of the selected clusters; therefore, the weight
      contribution of each cluster was obtained. Moreover, the other three unobserved
      peaks were all expected to be redshifted. According to these calculations and our
      understanding, in Y3Al5O12:Ce3+ nanocrystals, the shift of the peaks can be
      mainly attributed to the reduction of the crystal field felt by Ce3+ ions-which
      results in the reduction of the splittings of 5d levels of Ce3--as well as to the
      increase of the difference between the 5d average level and the 4f average level
      of Ce3+.

PMID- 22413246
TI  - Energy transfer mechanisms in Yb3+-doped GdVO4 near-infrared downconversion
      nanophosphor.
AB  - Yb3+-doped GdVO4 nanophosphor was prepared by the co-precipitation method. Under
      ultraviolet (UV) light excitation, strong near-infrared (NIR) emission of Yb3+
      (2F(5/2) --> 2F(7/2)) around 980 nm was observed. Owing to the host absorption of
      GdVO4, a broad excitation band ranging from 250 to 350 nm was recorded when the
      Yb3+ emission was monitored, which suggests an efficient energy transfer from the
      host to the Yb3+ ions. The concentration dependence of the visible vanadate
      emission and the Yb3+ emission was investigated. The decay curve of the vanadate
      emission was measured under the excitation of a 266 nm pulsed laser. The decay
      time of the vanadate emission at 500 nm was remarkably reduced by introducing
      Yb3+, further verifying that the energy transfer from the vanadate host to the
      Yb3+ ions was very efficient. Cooperative energy transfer (CET) is discussed as
      the possible energy transfer process. The temperature dependence of the emission
      intensity and decay time were also investigated for our further discussion.

PMID- 22413247
TI  - Continuous white luminescence of ZnS:Pb2+ and core/shell ZnS:Pb2+/ZnS
      nanocrystals.
AB  - High-quality water-soluble ZnS:Pb2+ nanocrystals were synthesized via a simple
      chemical codepositing method. The as-synthesized ZnS:Pb2+ nanocrystals show high
      monodispersity and crystallinity with a narrow size distribution (3.2 +/- 0.4
      nm). ZnS:Pb2+/ZnS core/shell structures were also obtained by coating a ZnS shell
      displaying significantly enhanced photoluminescence (PL) intensity and
      photostability. For the ZnS:Pb2+/ZnS samples the position of emission spectrum
      shows a red-shift of approximately 10 nm, which produces a fairly pure white
      emission with Commission Internationale de l'Eclairage (CIE) coordinates of
      (0.31, 0.33). These phenomena are explained by a model of multiple Pb2+
      luminescent centers.

PMID- 22413248
TI  - Luminescence efficiency enhancement of BaZr(BO3)2:Eu with Si or Al addition.
AB  - Si4+ and Al3+ doped BaZr(BO3)2:Eu phosphors were prepared by solidstate reaction.
      BaZr(BO3)2:Eu3+, BaZr(BO3)2:Eu3+, Si4+ and BaZr(BO3)2:Eu3+, Al3+ were
      characterized by X-ray diffraction spectra (XRD) and photoluminescence spectra.
      After codoped with Si or Al, the charge-transfer state (CTS) band of Eu3+-O(2-)
      shows blue shift accompanied by increasing intensity due to shorter ionic radius
      and stronger electro negativity of Si or Al compared with Zr4+. The high value of
      asymmetric ratio R(2-1) and omega2 of BaZr(BO3)2:Eu3+ with Si or Al codoping
      indicates a less symmetrical local structure of Eu3+. This implies that the
      quantum efficiencies of the 5D0 level of these complexes can be enhanced by
      doping with Si and Al respectively. Calculation of the Judd-Ofelt parameters of
      Eu3+ under different crystal fields gives similar results.

PMID- 22413249
TI  - Preparation and luminescence properties of La6MoO12:Eu3+/PVA nanofibers by
      Pechini/electrospinning process.
AB  - The 20% concentration Eu3+-based red-emitting phosphor, nano-sized La6MoO12:Eu3+
      was prepared by the Pechini method. X-ray diffraction (XRD), thermogravimetric
      and differential thermal analysis (TG-DTA), scanning electron microscopy (SEM),
      photoluminescence (PL), and decay curves were used to characterize the resulting
      samples. The phosphor can be efficiently excited by near UV light and exhibits an
      intense red luminescence corresponding to the electric dipole transition 5D0 -->
      7F2 at 615 nm. When the phosphor was mixed into poly(vinyl alcohol) aqueous
      solution, the fluorescent nanofibers could be prepared by electrospinning
      process. It was suggested that the La6MoO12:Eu3+ phosphor would be a promising
      red component for solid-state lighting devices based on InGaN or GaN light
      emitting diodes.

PMID- 22413250
TI  - Synthesis and upconversion luminescence of uniform beta-NaYF4:Yb3+/Tm3+ hexagonal
      nanoplates.
AB  - Yb3+ and Tm3+-codoped hexagonal-phase NaYF4 powders were prepared by a facile
      hydrothermal method. The results of X-ray powder diffraction (XRD) and scanning
      electron microscopy (SEM) showed that the as-prepared powders were well
      crystallized nanoplates with high size-uniformity. Under the excitation from a
      980 nm laser diode, upconversion (UC) emissions centered at approximately 291 nm
      (1I6 --> 3H6), approximately 346 nm (1I6 --> 3F4), approximately 361 nm (1D2 -->
      3H6), approximately 451 nm (1D2 --> 3F4), approximately 474 nm (1G4 --> 3H6),
      approximately 644 nm (1G4 --> 3F4), and approximately 799 nm (3H4 --> 3H6) were
      observed in the sample. Furthermore, the intensity dependence of UC emissions on
      excitation power was measured. The results indicated that populating the 1I6,
      1D2, 1G4, and 3H4 states were five-photon, four-photon, three-photon, and two
      photon UC processes, respectively.

PMID- 22413251
TI  - Sensitized upconversion emissions of Tb3+ by Tm3+ in YF3 and NaYF4 nanocrystals.
AB  - Yb3+-Tm3+-Tb3+-codoped YF3 and NaYF4 nanocrystals (NCs) were synthesized using a
      simple hydrothermal method. Under 980 nm excitation, violet and ultraviolet
      upconversion (UC) emissions of 5D3 --> 7FJ (J = 6, 5, 4) and 5D4 --> 7FJ (J = 6,
      5, 4, 3) of Tb3+ ions were observed with the fluoride NCs. In the Yb-Tm-Tb
      codoped NCs, energy transfer (ET) processes from Tm3+ to Tb3+ were proposed to be
      the main mechanisms for the UC emissions of Tb3+ ions. They are more efficient
      than the phonon assisted cooperative sensitization of the Yb3+ couple proposed
      previously for similar material system. The analysis of power dependence
      indicated that populating the 5D4 level of the Tb3+ ions was a four photon UC
      process, which demonstrated the existence of the two step ET process of Yb3+ -->
      Tm3+ --> Tb3+. It was also found that UC luminescence properties of Tb3+ ions
      were sensitive to crystal structures.

PMID- 22413252
TI  - Size dependent ultraviolet upconversion in single YF3:Yb3+/Tm3+ particles.
AB  - Yb3+-Tm3+ codoped YF3 bulk material was synthesized through a facile high
      temperature calcinations method. By grinding and selecting, the particles with
      different desired sizes in microns were obtained. Under 980 nm excitation,
      optical upconversion (UC) from near-infrared (NIR) to ultraviolet (UV) was
      studied for each group of particles for the effect of their size on UC. Comparing
      with the bulk sample, the micro-size particles exhibited strong ability for NIR
      to-UV UC. With the particle size decreasing from 800 microm to 20 microm, their
      UV emission intensities increased rapidly. Two possible mechanisms were proposed
      and discussed for clarifying the small size effect (SSE).

PMID- 22413253
TI  - Preparation and upconversion luminescence of Y2SiO5:Yb3+, Ho3+ nanophosphors.
AB  - X1 type monoclinic Y2SiO5:Yb3+, Ho3+ nanophosphors with fixed (varied) Ho3+ and
      varied (fixed) Yb3+ concentrations were synthesized by sol-gel method. The
      nanophosphors presented lacunaris shape with an average size of about 47 nm
      measured by transmission electron microscopy and scanning electron microscopy. Up
      conversion emissions have been observed at 550 nm corresponding to (5F4, 5S2)-5I8
      transition and 661 nm due to 5F5-5I8 transition of Ho3+ upon 980 nm excitation at
      room temperature. The results indicate that both green and red luminescences are
      based on the two-photon process through the energy transfer from Yb3+. However,
      the intensity of green emission is weaker than that of the red, because the 5I7
      level of Ho3+ can be effectively populated. The integrated upconversion emission
      intensity on the Yb3+ and Ho3+ concentrations were also studied.

PMID- 22413254
TI  - Effect of morphology of dispersed nano-CeO2 on far infrared emission property of
      natural tourmaline.
AB  - Dispersed nano-CeO2 successfully grew on the surface of natural tourmaline
      powders by a precipitation method. The results of Fourier transform infrared
      spectroscopy (FTIR) showed that CeO2 (111) nanospots could apparently enhance the
      far infrared emission property of tourmaline in relation to CeO2 nanoparticles.
      This is the first report regarding the effect of the morphology of nano-CeO2 on
      the far infrared emission property of natural tourmaline. The results of the
      characterization by transmission electron microscopy (TEM), X-ray diffraction
      (XRD), and X-ray photoelectron spectroscopy (XPS) showed that CeO2 (111)
      nanospots have much more chemisorbed oxygen than CeO2 nanoparticles, which is
      beneficial to the unit cell volume shrinkage of tourmaline, thus increasing its
      far infrared emissivity.

PMID- 22413255
TI  - Preparation and photocatalytic performance of iodine-doped NaTaO3 nanoparticles.
AB  - Iodine-doped NaTaO3 nanoparticles were prepared by hydrothermal conditions and
      explored as the visible-light-driven photocatalysts for photodegradation of
      methylene blue in water. It is found that I-doped NaTaO3 showed photodegradation
      efficiency superior over the un-doped NaTaO3. UV-Vis diffuse reflectance spectra
      indicate that the absorption edges shifted towards longer wavelength with
      increasing the iodine concentration. The energy band structure and the transient
      behavior of the photogenerated charge carriers for both un-doped and doped NaTaO3
      powders were investigated using density functional theory. The improved
      photocatalytic activity under visible light for I-doped NaTaO3 may be caused by
      both the broadening of valence band that inhibited the recombination of e-h+
      pairs and the narrowing of energy band gap due to the much negative energy levels
      in the bottom of conduction bands.

PMID- 22413256
TI  - Controllable multicolor upconversion luminescence of lanthanide doped NaGdF4
      nanocrystals through single laser excitation at 980 nm.
AB  - Room temperature multicolor Upconversion (UC) luminescence in Yb3+, Tm3+, Er3+
      ions doped NaGdF4 nanocrystals have been successfully synthesized by a
      hydrothermal method. As-prepared nanocrystals are highly crystalline and well
      dispersed in cyclohexane to form stable and clear colloidal solutions, which
      demonstrates strong emission properties with a single laser excitation at 980 nm.
      The multicolor light consists of blue, green, and red UC radiations that
      correspond to transitions 1G4 --> 3H6 of Tm3+, 2H(11/2)/4S(3/2) --> 4I(15/2), and
      4F(9/2) --> 4I(15/2) of Er3+ ions, respectively. The UC mechanisms were proposed
      based on spectral, kinetic, and pump power dependence analyses.

PMID- 22413257
TI  - Facile morphology-controlled synthesis and luminescence properties of BaMoO4:Eu3+
      microparticles and micro-rods obtained by a molten-salt reaction route.
AB  - This work focuses on the synthesis of morphology-controlled BaMoO4:Eu3+ micro
      crystals such as microparticles and micro-rods using a facile molten salt method,
      and their morphology, structural characterization, and luminescent properties
      were comparatively investigated by X-ray powder diffraction (XRD), scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), and
      fluorescence spectra. The molten salt method synthesized products from a reaction
      of BaMoO4 precursor obtained by a co-precipitation method of BaCl2 and Na2MoO4
      with an eutectic salt mixture of NaCl-KCl at 700 degrees C. Detailed studies
      revealed that the formation of the different morphologies of the micro-crystals
      was strongly dependent on the weight ratio of the salt (NaCl-KCl) to the BaMoO4
      precursor, and the formation mechanism of the products in the present molten salt
      system was also investigated. Based on the investigations of the
      photoluminescence properties, the samples with different morphologies prepared by
      the molten salt method had the strongest red emission at 615 nm, corresponding to
      the Eu3+ 5D0-7F2 transition in the BaMoO4 host lattice, and the emission
      intensity of BaMoO4:Eu3+ microparticles was stronger than that of BaMoO4:Eu3+
      micro-rods.

PMID- 22413258
TI  - The influence of synthesizing processes on the spectroscopic property of
      tetragonal LaOF:Eu3+ nanoparticles.
AB  - The tetragonal LaOF:Eu3+ nanoparticles have been successfully synthesized by
      three different methods including hydrothermal, solvothermal and chemical
      precipitation methods. Strong red fluorescence emissions were observed by
      exciting the samples with 532 nm laser. Under the proper conditions, the sample
      synthesized via chemical precipitation method presented the strongest
      fluorescence emission. It is found that the particle size, surface modification,
      crystal structure and local environment could be adjusted with different
      preparation processes.

PMID- 22413259
TI  - Surface enhanced fluorescence of physically polished nanostructured metal
      surface: the effect of the native oxide layer.
AB  - The fluorescence emission of Rhodamine 6G molecules at the physically polished
      nanostructured copper surface with varying thickness of the native oxide layer
      was investigated. The quenching effect was observed when the dye molecule was
      directly adsorbed onto the substrate surface without the formative oxide layer.
      However, the fluorescence was enhanced obviously when the native oxide layer was
      formed at the substrate surface. The experimental observations were discussed by
      taking into account the formation of the native oxide layer, the non-radiative
      energy transfer process and the local surface plasmon resonance at rough copper
      surface. The study highlights the importance of the native oxide layer formed on
      the metal substrate in surface enhanced fluorescence.

PMID- 22413260
TI  - Fabrication and luminescent enhancement of Eu3+-doped Y2O3@YOF core-shell
      nanocrystals.
AB  - In this paper, a two-step synthesis method for preparing Eu3+ ion-doped Y2O3@YOF
      core-shell nanocrystals is introduced. Eu3+ ion-doped Y2O3@YOF core-shell
      nanocrystals were prepared by combining an autocombustion process with a low
      temperature solid state reaction. X-ray powder diffraction (XRD), field emission
      scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM),
      energy dispersive X-ray spectroscopy (EDS), photoluminescence (PL) and
      fluorescence decay were employed to characterize the prepared samples. The
      results of XRD, TEM and EDS indicated that the products prepared by this method
      were not a mixture of Y2O3:Eu3+ and YOF:Eu3+ nanocrystals, but Eu3+ ion-doped
      Y2O3@YOF core-shell nanocrystals. Compared with Y2O3:Eu3+ nanocrystals, a 20%
      increment in luminescence intensity was observed in the Eu3+ ion-doped Y2O3@YOF
      core-shell nanocrystals, thus suggesting that coating with a YOF:Eu3+-shell can
      efficiently block the nonradiative relaxation channels that are induced by
      surface defect states.

PMID- 22413261
TI  - Terahertz response of ferroelectric nanofibers.
AB  - Far-infrared optical and dielectric properties of ferroelectric SrTiO3 and BaTiO3
      nanofibers, prepared by hydrothermal syntheses, were studied using terahertz time
      domain spectroscopy. The power absorption, refractive index, and complex
      dielectric function were characterized in the frequency range from 0.2 to 1.0
      THz. The measured results are well reproduced by theoretical fittings based on
      the dielectric models and the effective medium model. The study reveals that the
      low-frequency dielectric properties of the ferroelectric SrTiO3 nanofibers are
      associated with the lowest transverse optical (TO) soft mode TO1 at 2.70 THz
      (90.0 cm(-1)), and that of the ferroelectric BaTiO3 nanofibers are related to the
      lowest pair of transverse optical (TO) and longitudinal optical (LO) modes near
      5.35 THz, which are both consistent with their bulk single-crystal and thin-film
      counterparts.

PMID- 22413262
TI  - Soluble copper phthalocyanine applied for organic solar cells.
AB  - A soluble derivative of copper phthalocyanine, that is 2,9,16,23-tetra carboxyl
      copper phthalocyanine (CuTCPc), is synthesized in this paper. The applications of
      CuTCPc as donor and interlayer materials in solar cell devices are investigated.
      The results demonstrate that when CuTCPc is used as a donor material, the
      performance of the device ITO/CuTCPc/PCBM/Al shows an open circuit voltage
      (V(OC)) of 0.54 V, a short circuit current (J(SC)) of 0.825 mA/cm2, a fill factor
      (FF) of 32.3% and the power conversion efficiency (nu) of 0.14%. When CuTCPc acts
      as an interlayer, the performance of the device ITO/CuTCPc/P3HT:PCBM/Al is
      improved: J(SC) increases to 3.12 mA/cm2, V(OC) increases to 0.59 V, FF increases
      to 33.8%, and the corresponding nu is 0.62%.

PMID- 22413263
TI  - Efficient CdPbS quantum dots-sensitized TiO2 photoelectrodes for solar cell
      applications.
AB  - CdPbS quantum dots-sensitized TiO2 photoelectrode was prepared using chemical
      bath codeposition technique by dipping TiO2 film into a 0.5 M Cd(NO3)2-Pb(NO3)2
      solution (molar ratio 9:1) and a 0.5 M Na2S methanol solution. The CdPbS quantum
      dots have the size about 4 to 6 nm and distribute homogeneously in the TiO2 film.
      The as-prepared electrode showed improved absorption spectra. The assembled
      quantum dots-sensitized solar cell (QDSSC) yielded a power conversion efficiency
      (nu) of 1.88% and a short-circuit current of 15.28 mA/cm2 under AM 1.5
      illumination of 100 mW/cm2, far outperformed the single PbS, CdS QDSSC and the nu
      increased 49.2% than coupled PbS/CdS QDSSC. The solar cell presented IPCE peak
      value of 45.7% and the effective photovoltaic range covers the visible region and
      near infrared region.

PMID- 22413264
TI  - Bioactivity study of the titanium plates treated with microarc oxidation and
      alkali.
AB  - Microarc oxidation (MAO) and alkali treatment was used to modify the surface of
      titanium, which prepared different microstructure and nanostructure TiO2-based
      coating on titanium. The samples were analyzed by scanning electron microscopy
      (SEM), atomic force microscopy (AFM), X-ray diffraction (XRD), and contact angle
      measuring instrument. The sample's surface treated by MAO process was microporous
      structure and looks like a crate. In vitro bioactivity experiment indicated that
      the hydroxyapatite precipitates was as squama and grew perpendicularly on the
      sample's surface. In vitro cell culture and MTT assay the MAO-NaOH samples showed
      distinct proliferation levels compared to the MAO samples. It has no toxicity to
      the growth of MSC cell and had better biocompatibility. According to the
      calculation of surface energy, that better hydrophilicity of materials will
      induce the more growth of hydroxyapatite.

PMID- 22413265
TI  - Synthesis and characterization of [Eu(DBM)3phen]Cl3 @ SiO2-NH2 composite
      nanoparticles.
AB  - Fluorescent rare earth complex Eu(DBM)3(phen)]Cl3@SiO2-NH2 nanoparticles were
      synthesized by combination of solvent precipitation method and Stober method. The
      morphologies, structure, surface and optical properties of the samples were
      characterized by field emission scanning electron microscopy (FE-SEM),
      transmission electron microscopy (TEM), fourier transform infrared (FTIR)
      spectroscopy, thermal gravimetric analysis (TGA), differential scanning
      calorimetry (DSC), and fluorescence spectrophotometer (FS). The observation from
      FE-SEM images indicate that the obtained samples are spherical and uniform
      nanoparticles with a tunable average sizes from 140 nm to 300 nm. TEM results
      verify a core-shell structure of the nanoparticles. The FTIR spectrum confirms
      the characteristic vibration absorption peaks of the complex
      [Eu(DBM)3(phen)]Cl3@SiO2-NH2. TGA result indicates that the complex is stable
      below 200 degrees C. The photoluminescence analysis shows that the complex has
      Eu3+ characteristic red luminescence and broader excitation peak from 200 nm to
      450 nm that can meet the demands of fluorescent confocal imaging. The amino
      groups are directly introduced to the [Eu(DBM)3(phen)]Cl3@SiO2-NH2 nanoparticles
      surface by using APS (3-aminopropyl triethoxysilane). This makes the surface
      modification and bioconjugation of the nanoparticles easier. The nano-sized
      spheres could be provided a basis for further expansion of its application in
      biomedical imaging, biological detection and fluorescent nanoprobes.

PMID- 22413266
TI  - Effects of the introduced single-wall carbon nanotubes on the performance of blue
      phosphorescence organic light-emitting diodes.
AB  - In this paper, the effects of single-walled carbon nanotubes (SWCNTs) on the
      performance of blue phosphorescence organic light-emitting diodes (OLEDs) are
      investigated by altering the place of SWCNTs in prepared devices. Three kinds of
      OLEDs in which SWCNTs are spin-coated between the organic layer and the cathode
      or doped into the organic emitting layer or into the hole-injection layer are
      prepared. It is found that the SWCNTs doped into the hole-injection layer can
      enhance the current efficiency because the SWCNTs can reduce hole transport
      ability and balance two kinds of carriers. Even though SWCNTs doped into the
      organic emitting layer can improve the transport characteristics of polymer,
      excess holes lead to an imbalance of holes and electrons in the organic layer,
      and a lower current efficiency is obtained. SWCNTs located between the organic
      layer and the cathode can enhance the electron injection from the cathode to the
      organic layer, and the luminance and current efficiency characteristics are
      effectively improved.

PMID- 22413267
TI  - Synthesis and infrared property of polyaniline/phase-change nanocapsule
      composite.
AB  - A composite of polyaniline (PANI) and nanoencapsulated phase-change material
      (PCM) with polystyrene (PS) as the shell and n-octadecane as the core was
      synthesized using the ultrasonic technique assisted by in situ polymerization.
      The composite's morphology, structure, and thermal properties were characterized
      by transmission electron microscopy (TEM), X-ray powder diffraction (XRD),
      Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis
      (TGA), and differential scanning calorimetry (DSC). The results showed that the
      surface of the PCM nanocapsules was covered with PANI. The phase-change
      temperature of the nanocapsules of PCM and the composite was slightly lower than
      that of n-octadecane. Their latent heat was less than the calculated value based
      on the mass ratio of n-octadecane measured by TGA. The infrared emission
      properties of PANI, the phase-change nanocapsule, and the composite were studied
      using an IR-II infrared emissivity instrument and an infrared camera. It was
      found that the infrared emissivity of the composite was appreciably higher than
      that of PANI. However, the composite showed lower temperature than the PANI when
      observed by infrared camera with the increasing ambient temperature around the n
      octadecane phase-change temperature. This occurred because the phase-change
      material in the composite absorbs so much heat that infrared emissions were
      obviously decreased when the ambient temperature rose.

PMID- 22413268
TI  - Synthesis and characterization of Y2O3:Er3+ upconversion materials with
      nanoporous structures.
AB  - Y2O3:Er3+ upconversion materials with nanoporous structures were prepared by a
      hydrothermal method following a post-thermal treatment. The structure and
      morphology of the materials were characterized by X-ray diffraction (XRD) and
      field-emission scanning electron microscopy (FESEM). The results indicated that
      the as-obtained Y2O3:Er3+ powders were of cubic-phase structure, and the
      nanoporous structure was formed in the annealing process. The optical results
      indicated that high annealing temperature could improve the upconversion
      properties, but it could destroy the nanoporous structure. Under 980 nm
      excitation, red (4F(9/2) --> 4I(15/2) and green (2H(11/2), 4S(3/2) --> 4I(15/2))
      upconversion luminescence was observed. The studies on the intensity dependence
      of upconversion emission indicated that two-photon processes were responsible for
      the green and red upconversion luminescence. This kind of multifunctional
      material has potential applications in nanocontainers for use as biomolecule and
      drugs carriers.

PMID- 22413269
TI  - Electronic structure and optical properties of Al-doped ZnO.
AB  - Impure ZnO materials are of great interest in optic and electronic applications.
      In this work, the effects of Al-doping on the electronic structures of ZnO system
      are investigated in detail. We find that the crystal structure strains
      significantly due to the introduction of Al impurity. On the other hand, the
      electronic band structures show that the position of the Fermi level moves
      upwards and the bands split near the band gap due to the introduction of Al. This
      is attributed to the interaction between Al3p and Zn4s orbital, which tend to
      drive the system towards semimetal. Photoluminescence (PL) studies indicate that
      the Al-doped ZnO samples have a high density of defects. This can be explained
      qualitatively by the above analysis on electronic structure.

PMID- 22413270
TI  - Structure, charge-transfer and luminescent properties bis(2-methyl-8
      hydroxyquinoline) gallium chloride.
AB  - Bis(2-methyl-8-hydroxyquinoline) Gallium Chloride (GaMq2Cl) has been synthesized
      and characterized by X-ray crystallography. It is known from X-ray diffraction
      data on single crystals that the crystals of GaMq2Cl were monoclinic, space group
      C2/c, a = 28.701 A, b = 9.5405 A, c = 15.1434 A, Z = 8. Its thermal stability,
      electron structures and structural stability were investigated by TG analysis and
      quantum chemical calculations. The complex was a thermally stable material, with
      decomposition temperature being 348 degrees C. The electron-transfer property of
      GaMq2Cl is of advantage over hole-transfer property. Under UV excitation at 365
      nm, the complex emits blue fluorescence with the maximum emission peak at 471 nm.
      Finally, blue-green light-emitting devices using this complex as the emissive
      layer were also fabricated and investigated, with emission wavelength at 502 nm.
      The results promote GaMq2Cl as a good candidate for luminescent material.

PMID- 22413271
TI  - Shape controlled synthesis and photoluminescence properties of Eu3+-doped REVO4
      nanophosphors.
AB  - Eu3+-doped REVO4 nanphosphors were controllably synthesized by an EDTA-mediated
      hydrothermal method at 180 degrees C using RE(NO3)3 and Na3VO4 as precursors. The
      obtained products were characterized by X-ray powder diffraction (XRD), scanning
      electron microscopy (SEM), Fourier transform infrared spectrometry (FTIR), X-ray
      photoelectron spectra (XPS), and photoluminescence spectroscopy (PL). The XRD
      results showed that the products were pure tetragonal structure and no other
      impurity phase appeared. The PL studies demonstrated Eu3+ ions doping effectively
      enhanced luminescent properties of LaxRE(1-x)VO4 and YxRE(1-x)VO4 nanoparticles,
      but EU3+ ions doping did not enhance luminescent properties of CexRE(1-x)VO4 (x
      not equal 0) nanoparticles. The prepared phosphors showed well-defined red
      luminescence due to radiative transitions from 5D0 to 7F(J) (J = 1,2) levels of
      Eu3+ ions, respectively. Furthermore, we reported Eu3+-doped CexRE(1-x)VO4 (x not
      equal 0) phases represented a new class of optically inactive materials.

PMID- 22413272
TI  - Upconversion emission from Yb3+ and Tm3+ codoped NaYF4 thin film prepared by
      thermal evaporation.
AB  - Yb3+ and Tm3+ codoped fluoride thin film, with intense ultraviolet and visible
      upconversion emissions under 980 nm excitation, has been deposited on an Al2O3
      ceramic substrate by thermal evaporation under high vacuum.
      NaY(0.835)Yb(0.15)Tm(0.015)F4 bulk material synthesized by high temperature solid
      state reaction was used as target in preparing the thin film. Yb3+ and Tm3+
      codoped system, which had been reported before, had been studied. Compared with
      the unannealed thin film, the annealed film showed better upconversion emission
      properties, especially in the ultraviolet region, given in the normalized
      upconversion emission spectra, due to the structure changed from amorphous to
      hexagonal NaYF4 (beta-NaYF4) during the annealing process. The upconversion
      mechanism of the thin film was also discussed in this paper.

PMID- 22413273
TI  - Study on NIR optical rewritable film based on dithienylethene and upconversion
      nanocrystals.
AB  - Tm3+ and Yb3+ codoped NaYF4 upconversion (UC) nanoparticles (NPs) with intense
      ultraviolet (UV) fluorescence were synthesized using a solvothermal approach. NIR
      optical rewritable film incorporated with the UCNPs and dithienylethene (DTE)
      were performed for optical storage based on the photochromic reaction of DTE
      induced by the intense UV from themultiphoton UC fluorescence of NaYF4NPs. The
      photochromic DTE did not exhibit obvious fatigue after repetitious write/erase
      cycles using NIR/green irradiation.

PMID- 22413274
TI  - Up-conversion emissions characteristics of non-aqueous sol-gel derived RE3Al5O12
      nanocrystals.
AB  - The RE3Al5O12 (REAG:Er3Al5O12, Er:Y3Al5O12 and Er:Yb3Al5O12) up-conversion (UC)
      nanocrystals have been prepared by the non-aqueous sol-gel method. The green and
      red UC emissions are attributed to the 2H(11/2), 4S(3/2) --> 4I(15/2) and 4F(9/2)
      --> 4I(15/2) transitions of Er3+, respectively, were obtained for all samples
      with a 975 nm semiconductor LD excitation. For Er3Al5O12 nanocrystals, the green
      and red UC emissions have similar intensities. Y and Yb ions have no evident
      effect on the peak positions, but strongly affected the intensities of the green
      and red UC emissions of the Er. A much higher intensity of the green relative to
      red UC emission was observed for Er:Y3Al5O12 nanocrystals, however, the red UC
      emission became predominant for Er:Yb3Al5O12 nanocrystals. It was suggested that
      the two-photon process was responsible for the green and red UC emissions
      mechanism for all the samples.

PMID- 22413275
TI  - Up-conversion fluorescence of Tm3+ and Gd3+ in Yb3+/Tm3+ co-doped Gd2O3
      nanocrystals.
AB  - Through a co-precipitation method Gd(OH)3:20%Yb3+, 1%Tm3+ nanorods were
      synthesized. After sintered at 900 degrees C for 1 h in air, the as-prepared
      Gd(OH)3:20%Yb3+, 1%Tm3+ nanorods were converted into Gd2O3:20%Yb3+, 1% Tm3+
      nanocrystals. Crystalline phases, sizes, and morphologies of the two samples were
      characterized by X-ray diffraction and field emission scanning electron
      microscope. The up-conversion (UC) fluorescence spectra of the Gd2O3:20%Yb3+,
      1%Tm3+ nanocrystals were recorded by using a fluorescence spectrophotometer with
      a 980 nm continuous wave laser diode as excitation source. The nanocrystals not
      only present characteristic blue and ultraviolet (UV) UC emissions of activated
      Tm3+, but also show UV UC emissions of host Gd3+. The experimental study suggests
      that the excitation power has great effects on UC fluorescence properties and the
      energy transfer from Tm3+ to Gd3+ is very efficient.

PMID- 22413276
TI  - Fabrication of (Nd(0.01)La(x)Y(0.99-x))2O3 nanoparticles and transparent ceramics
      by combustion synthesis.
AB  - Y2O3 acts as the matrix material when doped with different content of La2O3 for
      reducing sintering temperature and refining grains. The (Nd(0.01)La(x)Y(0.99
      x))2O3 nanoparticles and transparent ceramics are fabricated by a combustion
      synthesis. The powder feature is characterized by TEM. The microstructure,
      mechanical properties and transmittance of the samples are examined by SEM, HV
      1000 hardness tester and fluorescence analyzer respectively. The results show
      that the (Nd(0.01)La(x)Y(0.99-x))2O3 nanoparticles are homogeneous in size and
      nearly spherical with average diameter in the range of 40-60 nm. There are no
      other phases except the Y2O3 cubic phase in the (Nd(0.01)La(x)Y(0.99-x))2O3
      nanoparticles. The grains of the samples significantly reduce with increasing
      La2O3 content. The hardness and fracture toughness increase rapidly first and
      then gradually tend to plateau with increasing La2O3 content. The transmittance
      of sample also increases gradually with increasing La2O3, the largest
      transmittance exceeds 77% when the La2O3 content is x = 0.12.

PMID- 22413277
TI  - Microstructural and photoluminescence properties of tin dioxide modified by
      electron beam irradiation.
AB  - A modified technique was developed by electron beam irradiation to prepare tin
      dioxide (SnO2) nanocrystals using the sol-gel method. SnO2 nanoparticles were
      radiated under a 1,400 KGy dose. The morphology and microstructure of the SnO2
      nanocrystals were investigated by X-ray diffraction, high-resolution transmission
      electron microscopy (HRTEM), and Raman spectroscopy. The results indicate that
      the irradiated SnO2 nanoparticles have better crystallinity than unirradiated
      SnO2 nanoparticles, and the resulting nanocrystals have a tetragonal rutile
      crystalline structure. The HRTEM image proves that the average grain size is
      about 4 nm, and the clear lattice fringes indicate the improvement of SnO2
      nanocrystals after irradiation. The Raman spectrum shows that there are new peaks
      at 535 cm(-1) and 691 cm(-1). The optical properties of SnO2 nanoparticles were
      characterized by ultraviolet-visible (UV-vis) and photoluminescence
      spectrophotometers. The band gap energy of the irradiated SnO2 was 3.29 eV
      smaller than that of the unirradiated SnO2 due to size effects and some defects
      of SnO2 nanocrystals. This work provides a novel approach for the improvement of
      SnO2 nanocrystals. The optical properties of the irradiated SnO2 nanomaterials
      are also expected to improve.

PMID- 22413278
TI  - Study on energy transfer and energy migration of Ca2Gd8(SiO4)6O2:Dy3+ phosphor
      films.
AB  - Being a kind of rare-earth-metal silicate with oxidapatite structure,
      Ca2R8(SiO4)6O2 (R = Y, Gd, La) is a promising material doped with rare earth, and
      widely used as phosphors. In this thesis, Ca2Gd8(SiO4)6O2:Dy3+ films were
      prepared by the sol-gel method. X-ray diffraction (XRD), atomic force microscopy
      (AFM), photoluminescence (PL) spectra, and lifetimes were used to characterize
      the resulting films. AFM study indicated that the phosphor films consisted of 120
      nm homogeneous particles. By combining the model of Burshtein for donor-donor
      migration and the V-F-B model for donor-acceptor energy transfer, the
      experimental luminescence decay curve of 6P(J) state of Gd3+ was re-simulated. It
      is found that concentration quenching of Gd3+ can be due to the result of the
      joint action of donor-donor (Gd3+-Gd3+) energy migration and donor-acceptor (Gd3+
      Dy3+) energy transfer.

PMID- 22413279
TI  - Investigation of the enhancement fluorescence of ethanol doped SiO2
      nanoparticles.
AB  - As one of the most commonly used solvents, ethanol exhibits weak fluorescence
      when excited by ultraviolet (UV) light. Until now, the fluorescence of ethanol
      doped nanoparticles has not been studied. In this paper, eleven different
      concentrations of SiO2 nanoparticles (diameter 100 nm) were doped in ethanol, and
      corresponding colloids were formed. The excitation and emission spectra of the
      colloids were measured. The experimental results indicated that the SiO2
      nanoparticles obviously enhanced the fluorescence of ethanol. Under excitation at
      306 nm, the enhancement effect is the best when the concentration of SiO2
      nanoparticles is 4.452 x 10(12) ml(-1), and the enhancement factor is nearly 50
      times at the peak position of 360 nm. At the excitation wavelength of 360 nm, the
      enhancement effect is the best when the concentration of SiO2 nanoparticles is
      1.113 x 10(13) ml(-1), and the enhancement factor is nearly 40 times at the peak
      position of 397 nm. The result of this article will reduce the test limit of
      ethanol by two magnitudes.

PMID- 22413280
TI  - Fluorescence enhancement of modified silver nanoparticles.
AB  - Surface enhanced fluorescence (SEF) effect of acridine orange fluorophore in the
      proximity of silver nanoparticles (NPs) has been investigated experimentally in
      the aqueous solution system. It was found that the SEF effect could be influenced
      by the distribution of the NPs and the separation between the fluorophore
      molecule and metal surface. The fluorescence enhancement was improved
      significantly when Ag NPs was capped with 4-Aminothiophenol (PATP) that was acted
      as an isolating layer between the metal surface and fluorophore molecules. The
      results suggest that a proper distribution of metallic NPs and proper separation
      between fluorophore molecule and the particle surface are important for obtaining
      an optimal SEF effect.

PMID- 22413281
TI  - Detection of Epstein-Barr virus infection in gastric carcinomas using quantum dot
      based fluorescence in-situ hybridization.
AB  - Quantum dots were proposed as new fluorochromes for use in fluorescence in-situ
      hybridization. EBV-encoded small RNA, the most abundant viral product in latently
      infected cells, was detected by quantum dot fluorescence in-situ hybridization in
      paraffin-embedded tissue sections of gastric carcinoma. An indirect FISH approach
      using quantum dots streptavidin conjugates as secondary reporters and digoxigenin
      labeled EBV-encoded small RNA oligonucleotide probes as detectable molecules was
      employed. Quantum dot fluorescence in-situ hybridization offered a slightly
      higher sensitivity in detecting EBV-encoded small RNA in gastric carcinoma than
      chromogenic in-situ hybridization. Statistical analyses showed that the detected
      EBV-associated gastric carcinoma was not associated with any clinicopathological
      parameters of the Chinese gastric carcinoma patients investigated in this study.

PMID- 22413282
TI  - Removal and recovery of lead (II) ions from contaminated licorice extracts using
      oxidized multi-walled carbon nanotubes.
AB  - A column with oxidized multi-walled carbon nanotubes (MWNTs) has been studied as
      a sorbent for removing and accumulating lead (II) from contaminated Licorice
      extracts. Under optimized situation, the adsorption capacity of lead (II) on
      oxidized MWNTs was 17 mg g(-1) at pH 7.0, and the lead (II) was eluted with 10 ml
      of 1% hydrochloric acid. Additionally, the effects of adsorptive parameters,
      including pH of the solution, sample volume, flow rates of the sample, matrix
      ions, and eluent type were investigated for optimization of the presented
      procedure. A fluorescence spectrophotometer was employed to determine the
      contents of lead (II). High-performance liquid chromatography (HPLC) was
      developed for the quantitative determination of main constituents of Licorice
      extracts. Oxidized MWNT cartridges were used to remove lead ions from
      contaminated Licorice extracts, high adsorption capacity, adsorption
      reversibility of lead (II), and low loss of major constituents. The results
      suggested that the oxidized MWNT column has the potential to remove heavy metal
      ions from herbal extracts.

PMID- 22413283
TI  - The fabrication and property of hydrophilic and hydrophobic double functional
      bionic chitosan film.
AB  - A new kind of hydrophobic bionic chitosan film was fabricated by simulating the
      surface structure of lotus leaf. The titanium oxide nanotube array was used as
      templates. Scanning electron microscopy (SEM) images show that one side of this
      films have nano-scale rough surface with spherical protrusions alike the surface
      of lotus leaf. The diameter of the protrusions is about 100 nm, which is equal to
      diameter of the titanium oxide nanotube. The water contact angle of chitosan
      films is up to 120 degrees and it is hydrophobic. The other side of the film is
      flat and the contact angle is 70 degrees. That indicated that the hydrophilism of
      natural materials is connected with the surface structures. The double functional
      chitosan films, one side is hydrophilic, the other is hydrophobic, can be made by
      an easy method. This method is non-toxic and clean. The double functional
      chitosan film will improve the application of chitosan films in medicine.

PMID- 22413284
TI  - Nitrogen doped ZnO thin films prepared by photo-assisted metal-organic chemical
      vapor deposition.
AB  - Nitrogen-doped ZnO (ZnO:N) films were prepared by photo-assisted metal-organic
      chemical vapor deposition technique using NH3 as N doping source. The effects of
      in-situ light irradiation on the properties of ZnO:N films were studied by Hall
      measurements, X-ray diffraction, Raman scattering, and X-ray photoelectron
      spectroscopy. The results show that stable p-type ZnO:N films with a hole
      concentration of 3.61 x 10(17) cm(-3) was successfully achieved. Moreover,
      introducing proper in-situ light irradiation during the growth process can not
      only effectively improve the crystalline quality of ZnO films, but also enhance
      the activity of (N)o (N occupies O site) acceptors by removing the undesirable
      hydrogen atoms from ZnO:N films. Both effects are benefit for the p-type
      conductivity formation. Our results indicate that photo-assisted MOCVD maybe an
      effective technology to realize device-quality p-type ZnO:N films.

PMID- 22413285
TI  - Preparation of porous titania film and its application in solar cells.
AB  - Polymer/nanocrystal bulk heterojunction photovoltaic cells have attracted
      substantial interest because the hybrid active layer combines the advantages of
      inorganic materials and polymers. In this work, a porous TiO2 was prepared via
      the sol-gel method with a polyethylene glycol 2000 (PEG2000) template. A kind of
      polymer/inorganic solar cell based on poly (3-hexylthiophene) (P3HT)/TiO2 was
      fabricated on the indium-tin-oxide (ITO) glass substrate and the structure of
      device was ITO/TiO2/P3HT/Au. The device showed the performance with a short
      circuit current (J(SC)) of 1.29 mA/cm2, an open circuit voltage (V(OC)) of 0.55 V
      and a fill factor (FF) of 28.7%.

PMID- 22413286
TI  - Modified spontaneous emission of organic molecules in-filled in inverse opals.
AB  - Inverse opals were prepared by replication of colloidal crystal templates made
      from silica spheres 298 nm in diameter. The air between the silica spheres was
      filled with the mixture of the monomer poly(methyl methacrylate) (PMMA) and the
      organic molecule Alq3 that can be subsequently polymerized. After removing the
      silica sphere templates, the photonic bandgap effect on the spontaneous emission
      of Alq3 were investigated. The dip in the fluorescence spectrum was interpreted
      in terms of redistribution of the photon density of states in the photonic
      crystal.

PMID- 22413287
TI  - Study the formation mechanism of silicon carbide polytype by silicon carbide
      nanobelts sintered under high pressure.
AB  - In this paper, in order to reveal the formation mechanism of SiC polytype, four
      SiC specimens sintered under high pressure has been investigated, after being
      prepared from SiC nanobelts as initial powders. The structure and morphology
      variation dependence of SiC specimens with temperature and pressure was studied
      based on experimental data obtained by XRD, SEM, and Raman. The results show that
      SiC lattice structure and the crystallite size are greatly affected by pressure
      between 2 and 4 GPa under different sintering temperatures of 800 and 1200
      degrees C. At the largest applied pressure and temperature, 4 GPa and 1200
      degrees C, 3C-SiC crystal structure can be changed into to R-SiC due to the
      stress resulted in dislocations instead of planar defects. Based on our results,
      the multiquantum-well structure based a single one-dimensional nanostructure can
      be achieved by applying high pressure at certain sintered temperature.

PMID- 22413288
TI  - Y2O3:Eu3+ core-in-multi-hollow microspheres: facile synthesis and luminescence
      properties.
AB  - Y2O3:Eu3+ core-in-multi-hollow microspheres were synthesized via a facile
      hydrothermal method in the presence of glucose followed by a subsequent heat
      treatment process. X-ray diffraction (XRD) pattern shows that the as-obtained
      hollow spheres are cubic phase of Y2O3. Field emission scanning electron
      microscopy (FESEM) and transmission electron microscopy (TEM) images indicate
      that the samples are three layer hollow spheres with a diameter of 2-4 microm and
      the outermost wall thickness of 100 nm, the size of the inner core is about 300
      400 nm, and the sub-outer wall thickness is about 100 nm. X-ray energy dispersive
      spectrum (EDS) shows that the samples are composed of Y, Eu and O.
      Photoluminescence spectra show that the hollow spheres have a strong
      characteristic red emission corresponding to the 5D0 - 7F2 transition of Eu3+
      ions under ultraviolet excitation. This method can be used to synthesize other
      rare earth oxide hollow luminescent materials.

PMID- 22413289
TI  - Synthesis and upconversion luminescence of NaYF4:Yb, Tm/TiO2 core/shell
      nanoparticles with controllable shell thickness.
AB  - NaYF4:Yb, Tm/TiO2 core/shell nanoparticles were synthesized by a two-step method.
      First, the NaYF4:Yb, Tm nanocrystals were prepared using solvothermal technology;
      then, TiO2 shells were deposited on the nanocrystals by the hydrolysis of
      titanium ethoxide (TEOT) to form core/shell structures. By controlling the
      reaction time, we can adjust the thickness of TiO2 shell and thereby the weight
      percentage of TiO2 in the core/shell nanoparticles. The effect of shell thickness
      on the upconversion fluorescence of NaYF4:Yb, Tm nanocrystals was investigated in
      detail.

PMID- 22413290
TI  - Ultraviolet upconversion fluorescence of Er3+ in Yb3+/Er3+-codoped Gd2O3
      nanotubes.
AB  - Under 980 nm excitation, room-temperature ultraviolet (UV) upconversion (UC)
      emissions of Er3+ from the 4G(9/2), 2K(13/2), and 2P(3/2) states were observed in
      Gd2O3:Yb3+/Er3+ nanotubes, which were synthesized via a simple wet-chemical route
      at low temperature and ambient pressure followed by a subsequent heat treatment
      at 800 degrees C. The experimental results exhibited that these UV emissions came
      from four-photon UC processes. In the Gd2O3:Yb3+/Er3+ nanocrystals, the energy
      transfers (ETs) from Yb3+ to Er3+ played important roles in populating the high
      energy states of Er3+ ions. This material provides a possible candidate for
      building UV compact solid-state lasers or fiber lasers.

PMID- 22413291
TI  - Synthesis and characterization of upconverting NaYF4:Er3+, Yb3+ nanocrystals via
      thermal decomposition of stearate precursor.
AB  - Er3+-Yb3+ codoped hexagonal NaYF4 nanocrystals were prepared via a method of
      thermal decomposition of stearate precursor. Their crystal structure,
      morphologies and photoluminescence (PL) properties were characterized by XRD,
      SEM, and fluorescence spectra. The hexagonal NaYF4:Er3+, Yb3+ nanocrystals could
      be well dispersed in cyclohexane to form a clear solution. Under 980 nm
      excitation, the solution of Er3+-Yb3+ codoped NaYF4 nanocrystals emits bright
      green upconversion fluorescence.

PMID- 22413292
TI  - Synthesis of the Fe3O4@SiO2@SiO2-Tb(PABA)3 luminomagnetic microspheres.
AB  - In this paper, we describe the synthesis and characterization of a luminomagnetic
      microspheres with core-shell structures (denoted as Fe3O4@ SiO2 @SiO2-Tb(PABA)3).
      The luminomagnetic microspheres were characterized by field emission scanning
      electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier
      transform infrared spectroscopy (FT-IR), vibrating sample magnetometer (VSM), and
      photoluminescence spectrophotometer (PL). The SEM observation shows that the
      microsphere consists of the magnetic core with about 400 nm in average diameter
      and silica shell doped with terbium complex with an average thickness of about 90
      nm. It has a saturation magnetization of 15.8 emu/g and a negligible coercivity
      at room temperature and exhibits strong green emission peak from 5D4 --> 7F5
      transition of Tb3+ ions. The luminomagnetic microspheres with good magnetic
      response and fluorescence probe property as well as water-dispersibility would
      have potential medical applications, such as time-resolved fluoroimmunoassay (TR
      FIA), fluorescent imaging, and magnetic resonance imaging (MRI).

PMID- 22413293
TI  - Study on luminescent properties of Eu3+ doped new type yttrium tungsten oxide
      nanophosphors.
AB  - In this paper, a novel nanophosphor, Y10W2O21:Eu, was synthesized through co
      precipitation which is a simple and low-costing method. The structure and
      morphology of the nanocrystal samples were characterized by using XRD and FE-SEM.
      The emission spectra, excitation spectra and fluorescence decay curves were
      measured. J-O parameters, quantum efficiencies of Eu3+ 5D0 energy level, color
      coordinates and Huang-Rhys factor of Y10W2O21:Eu nanophosphors were calculated.
      The results indicate that EU3+ 5D0-7F2 red luminescence at 610 nm can be
      effectively excited by 394 nm near-UV light and 464 nm blue light in Y10W2O21
      host, which is similar to the familiar Eu3+ doped tungstate phosphors (e.g.,
      Gd2(WO4)3:Eu, CaWO4:Eu). Besides, compared with the other types of tungstate
      phosphors, a less expensive tungsten was used, which can effectively reduce cost.
      Therefore, the Y10W2O21:Eu red nanophosphors may have a potential application for
      white LED.

PMID- 22413294
TI  - Synthesis and characterization of PVP/TbL(phen)0.5 x 7H2O nanorods.
AB  - The luminescent complex terbium (III)-trimesic acid (TMA)-1,10-phenanthroline
      (phen) nanorod was synthesized in the polyvinylpyrrolidone (PVP) matrix by a co
      precipitation method. The chemical formula of the synthesized complex was
      speculated to be PVP/TbL(phen)0.5 x 7H2O by inductively coupled plasma-atomic
      emission spectroscopy (ICP-AES), elemental analysis and Fourier-transform
      infrared spectroscopy (FTIR). The X-ray diffraction pattern (XRD) of
      PVP/TbL(phen)0.5 x 7H2O indicated that it was a crystalline complex. The
      transmission electron microscopy (TEM) result showed that the complex was
      nanorods with diameters of about 80-100 nm. The thermogravimetric curve (TGA)
      analysis exhibited that the complex has good stability below 400 degrees C. UV
      Vis diffuse reflectance spectra showed that there is a maximum absorption at 300
      nm. The photoluminescence analyses (PLA) showed that the synthesized complex
      emitted the characteristic green fluorescence of Tb (III) ions under ultraviolet
      light excitation. The emission peaks of PVP/TbL(phen)0.5 x 7H2O at 488, 542, 581,
      and 618 nm using 278 nm as exciting wavelength can be assigned to the 5D4 -->
      7F6, 5D4 --> 7F5, 5D4 --> 7F4, and 5D4 --> 7F3 electron transitions of the Tb3+
      ions, respectively.

PMID- 22413295
TI  - Self-assembly deposition and luminescence properties of TiNbO5(-) and TiTaO5(-)
      nanosheets.
AB  - Through a novel mechanical cleavage technology, TiNbO5(-) and TiTaO5(-)
      nanosheets were obtained by the exfoliation of the layered KTiTaO5 and KTiNbO5.
      Lamellar aggregates of the pre-prepared nanosheets accommodating Eu3+ ions have
      been fabricated by flocculation of colloidal nanosheet. A series of methods
      including X-ray diffraction (XRD), transmission electron microscopy (TEM) were
      used to analyze the structure of the as-obtained composites. The results
      indicated that the restacking nanosheets could form a uniform layered structure.
      Meanwhile, the Eu3+ ions could enter into the interlayer of the flocculated
      nanosheets. The Photoluminescence (PL) spectra were also employed to investigate
      the optical property of the hybrids. The characteristic emission from the
      composites either by exciting the nanosheet host with UV light or by directly
      exciting RE at a longer wavelength were studied in details.

PMID- 22413296
TI  - Emission evolution of alpha-silicon nitride nanowires with temperature.
AB  - The photoluminescence and temperature dependent emission spectra of silicon
      nitride nanowires were investigated by using femtosecond pulse laser. Three
      discrete sharp emission peaks were observed in photoluminescence, which were
      significantly different from that pumping by low excitation intensity laser. The
      temperature effects on emission peak energy were extracted using Gauss function,
      and should be attributed to volume-temperature effect and phonon effect.

PMID- 22413297
TI  - Synthesis and characterization of nano-PVP/EuL3 luminescent complex.
AB  - Nano-sized rare earth europium [Eu(III)]-benzoic acid [HL] luminescent complex
      powders have been synthesized in polyvinylpyrrolidone matrix by precipitation
      method. The chemical constitution of the complex has been demonstrated as
      PVP/EuL3 by a combination of elemental analysis, inductively coupled plasma
      atomic emission spectroscopy (ICP-AES) and fourier-transform infrared
      spectroscopy (FT-IR). X-ray diffraction analysis (XRD) and scanning electron
      microscopy (SEM) have shown that the complex is a new nanocrystal whose structure
      is totally different from the ligand. Thermogravimetric/Differential thermal
      analysis (TG/DTA) have indicated that the luminescent complex is thermally stable
      below 500 degrees C. Photoluminescence spectra (PL) have shown that the
      nanocomplex can emit Eu3+ characteristic red fluorescence under ultraviolet
      excitation.

PMID- 22413298
TI  - Surface enhanced fluorescence of Rh6G with gold nanohole arrays.
AB  - Five gold nanohole arrays with distinct aperture size were fabricated by
      magnetron sputtering technique. Fluorescence enhancements of Rh6G fluorophore in
      the close vicinity of gold nanohole arrays were observed. Up to 40 times increase
      of fluorescence intensity was obtained from gold nanohole arrays as compared with
      a smooth gold surface control sample. A double-peak curve was presented in the
      excitation spectrum of enhanced fluorescence emission when the excitation
      wavelength was scanning from 300 nm to 550 nm. It was found that smaller aperture
      size and proper excitation wavelength matching with the surface plasmon
      resonances condition were favorable for a better fluorescence enhancement.

PMID- 22413299
TI  - Spectroscopic study of Eu3+ doped LaF, nanoparticles prepared with different PH
      values.
AB  - Europium doped lanthanide fluoride (LaF3) nanoparticles were prepared through a
      hydrothermal method with different PH values of precursor complex solution. The
      influence of PH value on the luminescence properties is investigated. It was
      found that the local symmetry of doped ions reduced with the increase of PH
      value, leading to the increase of the inversion symmetry ratio. The fluorescence
      quenching was observed for small nanoparticles, which was attributed to the large
      amount of OH groups absorbed to the surface of the nanoparticles.

PMID- 22413300
TI  - Preparation and photocatalytic activity of an electrostatically self-assembled
      film made of [PMo12O40](3-) and a bipolar hemicyanine cation.
AB  - An electrostatically self-assembled film of PMo12/H6 has successfully been
      prepared on quartz substrates by alternating adsorption of [PMo12O40(3-) (PMo12)
      and a bipolar hemicyanine derivative of (E)-1,1'-(hexane-1,6-diyl)bis(4-(4
      (dimethylamino)styryl)pyridinium) bromide (H6Br2). The UV-visible spectra showed
      that the film was uniformly deposited and the charge transfer between two film
      forming components might occur in the film. The photocatalytic performance of the
      film was studied for the degradation of aqueous dye Methyl Red (MR) under UV
      irradiation. The degradation of MR follows Langmuir-Hinshelwood first-order
      kinetics.

PMID- 22413301
TI  - Room-temperature synthesis of high-density CuS nanowire arrays by a simple paired
      cell.
AB  - High-density CuS nanoparticle nanowire (NPNW) arrays were successfully
      synthesized at room temperature by a simple paired cell method. The as-prepared
      nanowire arrays were characterized by X-ray diffraction (XRD), field emission
      scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS) and
      transmission electron microscopy (TEM). The results indicate that the nanowire
      diameter is dependent on the pore size of the used ordered porous anodic alumina
      (OPAA) template and larger than the corresponding pore diameter of the template
      due to the corrosion effect of Na2S solution on the template. The nanowire is
      composed of CuS nanoparticles with hexagonal structure. When the reaction time is
      long enough, the nanowire is solid and composed of nearly spherical CuS
      nanoparticles. When the reaction time is short, only middle part of the nanowire
      is solid and composed of nearly spherical CuS nanoparticles, however, the tops
      are hollow and mainly composed of flake-like nanoparticles. The formation
      mechanism of CuS nanoparticle nanowires was proposed to be a heterogeneous
      nucleation, coalescence, aggregation and filling process.

PMID- 22413302
TI  - Excitons emissions and Raman scattering of ZnO nanoparticles embedded in BaF2
      matrices by reactive magnetron sputtering.
AB  - ZnO nanoparticles embedded in BaF2 matrix were fabricated by rf magnetic
      sputtering technology. The optical properties of high quality ZnO nanoparticles,
      thermally post treated in a N2 atmosphere, were investigated by temperature
      dependence photoluminescence measurement. Free exciton and localized exciton were
      observed at the low temperature. Free exciton peak was at 3.374 eV and localized
      exciton peak was at 3.420 eV, dominating the PL spectrum at 77 K. Free exciton
      transition was observed at 3.310 eV at room temperature, whereas the localized
      exciton transition was at 3.378 eV. The multiple-phonon Raman scattering spectrum
      showed that ZnO nanoparticles embedded in BaF2 matrix had a large deformation
      energy originated from lattice mismatch between ZnO and BaF2 matrix. Analysis of
      the fitting results from the temperature dependence of FWHM of ZnO exciton
      illustrated that the large value of gamma(ph) was good qualitative agreement with
      the large deformation potential.

PMID- 22413303
TI  - Luminescence properties of nano-crystalline Ba3MgSi2O8:Eu2+, Mn2+ phosphors.
AB  - Ba3MgSi2O8:Eu2+, Mn2+ phosphors were synthesized by the sol-gel method and high
      temperature solid-state reaction method, respectively. XRD (X-ray diffraction),
      FT-IR (Fourier transform infrared spectroscopy), PL (photoluminescence spectra),
      and PLE (photoluminescence excitation spectra) were measured to characterize the
      samples. Emission and excitation spectra of our Ba3MgSi2O8:Eu2+, Mn2+ phosphors
      monitored at 441, 515, and 614 nm are depicted in the paper. The emission
      intensities of 441 and 515 nm emission bands increase with increasing Eu2+
      concentration, while the peak intensity of the 614 nm band increases with
      increasing Mn2+ concentration. We conclude that the 515 nm emission band is
      attributed to the 4f(6)5d transition of Eu2+ ions substituted by Ba2+ sites in
      Ba2SiO4. The 441 nm emission band originates from Eu2+ ions, while the 614 nm
      emission band originates from Mn2+ ions of Ba3MgSi2O8:Eu2+, Mn2+. Nano
      crystalline Ba3MgSi2O8:Eu2+, Mn2+ phosphors prepared by the sol-gel method show
      higher color rendering and better color temperature in comparison with the
      samples prepared by high temperature solid-state reaction method.

PMID- 22413304
TI  - Luminescence properties of nano-sized Sr2MgSiO5: Eu2+, Mn2+ phosphors prepared by
      the sol-gel method.
AB  - Nano-sized Sr2MgSiO5:Eu2+, Mn2+ phosphor was synthesized by the sol-gel method.
      The preparation conditions of the precursor were determined. The effect of Eu2+
      and Mn2+ content on the luminescence intensity was studied. X-ray diffraction
      (XRD), photoluminescence spectra (PL), and photoluminescence excitation spectra
      (PLE) were used to characterize the samples. The results showed that the
      excitation bands ranged from 250 to 450 nm, and their peaks positioned around 365
      nm. The emission spectrum consists of three bands: blue, green, and red,
      respectively. The blue and green emission bands originate from the center of the
      Eu2+, while the red emission band is attributed to the energy transfer from Eu2+
      to Mn2+. White light can be obtained by mixing the three emission colors. The
      experiment results show that the Sr2MgSiO5:Eu2+, Mn2+ is a single host phosphor
      with superior properties for use in white light emitting diodes (white LED).

PMID- 22413306
TI  - Oxygen sensing properties of Cu(I) complex/polystyrene composite nanofibers
      prepared by electrospinning.
AB  - The preparation and oxygen sensing properties of luminescence quenching oxygen
      sensing materials based on an electrospum composite nanofibers with
      [Cu(POP)DPPZ]BF4(POP = bis[2-(diphenylphosphino)phenyl]ether; DPPZ = dipyrido[2,3
      a:3',2'-c]phenazine) complex embedded within polystyrene (PS) matrix are
      described in this article. The luminescence of [Cu(POP)DPPZ]BF4 complex within
      the electrospum nanofibers can be efficiently quenched by oxygen with good
      sensitivity (I0/I100 = 5.54) and rapid response (3 s), which suggests that the
      Cu(I) complex/polystyrene composite nanofibers presented in this article can be
      used for developing oxygen sensors. The downward oxygen sensing Stern-Volmer
      plots can be attributed to the heterogeneous environment of the Cu(I) luminophore
      within the nanofibers. The high sensitivity is attributed to the low-dimensional
      structure of the nanofiber and its large surface area-to-volume ratio, which
      facilitates oxygen entry and diffusion.

PMID- 22413305
TI  - Synthesis and conductive properties of polypyrrole nanocomposites.
AB  - This paper studies the impact on the different surfactants and capacity of the
      oxidant for the synthesis of polypyrrole (PPy). The soluble PPy has also been
      studied. PPy was characterized mainly from the surface morphology, Fourier
      transform infrared spectroscopy, and conductivity sigma. First, using
      cetyltrimethylammonium bromide (CTAB) as the surfactant doped in an acid doping
      environment and without using ammonium persulfate (APS) as an oxidant, we
      determined the different capacities of the oxidant to synthesize the PPy.
      Scanning electron microscopy, Fourier transform infrared spectroscopy, and a four
      probe conductivity meter were used to characterize the PPy. The acid doping
      conductivity was found to be 25 S/cm higher. Then, the solubility of polypyrrole
      was studied by doping with sodium dodecyl benzene sulfonate (SDBS), polyethylene
      glycol (PEG), and poly(styrene sulfonate) (PSS), proceeding the above-mentioned
      characterization.

PMID- 22413307
TI  - Hydrothermal synthesis of one-dimensional single-crystalline rutile TiO2
      nanostructures and their application in dye-sensitized solar cells.
AB  - One-dimensional (1D) TiO2 nanowire arrays are fabricated on transparent
      conducting substrates via a low temperature hydrothermal route for application in
      dye-sensitized solar cells (DSSCs). The as-prepared sample on fluorine-doped tin
      oxide (FTO) substrate is found to be single-crystalline rutile TiO2 structures
      from X-ray and electron diffractions. The length and diameter of the nanowires
      depend mainly on the growth time and temperature. With increasing the reaction
      time, the growth rate becomes slower and the interface adhesion between the
      growth nanowires and the substrate becomes weaker. In the same time the adjacent
      nanowires aggregate to larger the apparent diameter of the nanowire making the
      gaps among the nanowires to disappear at last. The nanowires exhibit flower-like
      morphology on the non-conducting surface of FTO substrate. By using TiO2 nanowire
      arrays with 2 microm long on FTO substrate as the photoanode in DSSCs, an overall
      light conversion efficiency of 1.58% is achieved with an open circuit voltage of
      0.714 V, a short circuit current density of 4.68 mA cm(-2), and a fill factor of
      0.472.

PMID- 22413308
TI  - Synthesis and afterglow properties of MgAl2O4:Eu2+, Dy3+ nanopowders.
AB  - The MgAl2O4:Eu2+, Dy3+ nanophosphors with different particle sizes have been
      synthesized through a simple and inexpensive precipitate approach followed by a
      post-annealing process. The structure and morphology of the phosphor are
      characterized by X-ray diffraction (XRD) and transmission electron microscopy
      (TEM). According to XRD and TEM results, the particle size of MgAl2O4:Eu2+, Dy3+
      could be controlled via changing the ratio of MgSO4/Al2O3, and the obtained
      samples possess regular morphology. The afterglow properties of MgAl2O4:Eu2+,
      Dy3+ nanophosphors as a function of particle sizes are investigated by afterglow
      decay curves. Compared with the bulk phosphor, the nanophosphors exhibit longer
      afterglow time and higher initial afterglow intensity. In nanophosphors, there
      exist numerous defects on their surfaces due to the large surface to volume
      ratio, which generally act as luminescent killers, while some of which, however,
      can probably act as traps beneficial for the generation of afterglow. In the
      nanosized MgAl2O4:Eu2+, Dy3+ phosphor, the thermoluminescence results indeed
      indicate the existence of more traps which are introduced due to the large
      surface to volume ratio of nanoparticles and that the high temperature sintering
      process contributes to the longer afterglow in the nanophosphors.

PMID- 22413309
TI  - Self-assembled peanut-like Ln3+ (Ln = Tb, Sm, Eu) doped NaLa(WO4)2: phase control
      and its relevance to luminescence modification.
AB  - Ln3+ (Ln = Tb, Sm, Eu) doped NaLa(WO4)2 peanuts were successfully self-assembled
      by a facile EDTA assisted hydrothermal treatment. EDTA played critical roles in
      the phase and morphology control, which regulated the phase transformation from
      monoclinic La2(WO4)3 flowers to tetrahedral NaLa(WO4)2 peanuts. La2(WO4)3:Tb3+
      exhibited two broad excitation bands at 280 and 340 nm, which are related to the
      normal and perturb sites of WO4(2-). However, the excitation band for
      NaLa(WO4)2:Tb3+ shifted to near ultraviolet region and showed only one broad
      excitation band originating from perturb sites. Under ultraviolet excitation,
      La2(WO4)3:Tb3+ displayed green light and NaLa(WO4)2:Tb3+ showed blue-green light
      consisting of WO4(2-) self-activated blue emission and the characteristic Tb3+
      emission. It can be clearly seen that the blue emission of WO4(2-) was not
      sufficiently quenched in NaLa(WO4)2 as that in La2(WO4)3, because the distortions
      of crystalline lattice for NaLa(WO4)2 may alter the energy migration processes.
      When doping with Sm3+ and Eu3+, NaLa(WO4)2 peanuts exhibited white color emission
      which may find practical applications in solid state lighting devices.

PMID- 22413310
TI  - Preparation and electrochemical and electrocatalytic properties of nanocomposite
      multilayer film based on a Keggin-type phosphomolybdate.
AB  - An electrostatically self-assembled multilayer film has successfully been
      prepared on quartz or indium-tin-oxide substrates by alternating adsorption of a
      Keggin-type phosphomolybdate H3PMo12O40 (PMo12) and 1,10-diaminodecane (1,10
      DAD). The formation of (PMo12/1,10-DAD), film was investigated by ultraviolet
      (UV) spectroscopy. The UV spectra showed that the deposition of the films was
      uniform and reproducible. The cyclic voltammetry on the PMo12-based multilayer
      film indicated that the PMo12 anions in the film undergo rapid four 2e(-)/2H+
      redox processes, and electrocatalytically active towards the reduction of
      bromate.

PMID- 22413311
TI  - Growth and properties of Zn(1-x)CdxO and Zn(1-x)CdxO/ZnO core/shell
      nanoparticles.
AB  - Octylamine capped Zn(1-x)CdxO alloys and Zn(1-x)CdxO/ZnO core/shell nanoparticles
      have been grown by the thermal decomposing of zinc and cadmium cupferronates in
      organic solvents. Zn(1-x)CdxO alloys incorprated with different concentration of
      Cd have been grown by quickly injecting of their precursors at 200 degrees C.
      Zn(1-x)CdxO/ZnO core/shell nanoparticles are performed by slowly injecting of
      shell precursors at 180 degrees C. The prepared nanoparticles are characterized
      by X-ray diffraction, absorption spectrometer, Mirco-Raman spectrometer and
      transmission electron microscopy. The band gap of ZnCdO alloys shrinks linearly
      and the crystal lattice expands with an increase of Cd concentration. The growth
      of ZnO shells on ZnCdO cores enhances the core luminescence dramatically and
      results in a red shift in the absorption and emission of Zn(1-x)CdxO cores.

PMID- 22413312
TI  - Growth and properties of ZnO/Zn(1-x)MgxO core/shell nanoparticles.
AB  - ZnO/Zn(0.9)Mg(0.1)O core/shell nanoparticles have been grown by employing metal
      cupferronate complex as precursors in organic solvents. ZnO cores are grown by
      quickly injecting their precursor at 250 degrees C while the shells are performed
      by slowly injecting their precursors at different temperatures. The grown
      nanoparticles are characterized by X-ray diffraction, photoluminescence
      microscopy, and transmission electron microscopy. The effects of the shell growth
      temperatures and precursor injecting rate are studied. Zn(0.9)Mg(0.1)O shells can
      epitaxially grow on ZnO cores when the shell growth temperature is lowered to 200
      degrees C and the shell precursor is supplied slowly at a rate of 0.1 mmol/h.
      Increaseing shell supply rate or shell growth temperature results in homogenous
      growth of Zn(0.9)Mg(0.1)O nanoparticles. The shell growth can dramatically
      enhance core emission and cause a red shift on the core band edge emission.

PMID- 22413313
TI  - Stability and nonlinear optical properties of ZnO nanoparticles.
AB  - Photoluminescence (PL) of ZnO nanoparticles of different surface states and sizes
      grown by several methods has been measured. The origin of luminescence and
      dependence of the luminescence spectrum shape and intensity on 325 nm excitation
      laser power are studied. Strong ultraviolet emission at 3.26 eV, weak violet
      emission around 3.12 eV and weak green emission at 2.40 eV have been observed in
      16 nm nanoparticles capped by octylamine grown by non-hydrolytic method. The
      nanoparticles are stable under high power laser radiation and their PL intensity
      increases nonlinearly with an increasing laser power. As the nanoparticle size
      decreases to 12 nm, high power laser produces nonradiative centers which may
      quench the luminescence in a degree. Nanoparticles of 8 nm capped by PVP and
      uncapped nanoparticles of 14 nm are unstable and their luminescence depends on
      the excitation laser power. High power laser can quench O vacancy emission and
      enhance ultraviolet emission in PVP capped nanoparticles while vacancy emission
      can not be quenched in uncapped nanoparticles.

PMID- 22413314
TI  - Pressure dependence of Mn2+ fluorescence in MnS/ZnS core-shell quantum dots.
AB  - The high pressure photoluminescence spectra of MnS/ZnS core-shells quantum dots
      were measured using a diamond anvil cell up to 9.4 GPa. Orange emission at 590 nm
      from the 4T1 --> 6A1 transition of Mn2+ ions was observed. The Mn2+ emission
      shifted to red with increasing pressure. The experimental pressure coefficient
      was -48.3 meV/GPa, which is agreement with the calculated value based on the
      crystal field theory. The redshift is attributed to the increase of crystal field
      strength and decrease of Racah parameters during compression.

PMID- 22413315
TI  - High pressure luminescence and Raman studies on the phase transition of
      Gd2O3:Eu3+ nanorods.
AB  - The cubic Gd2O3:Eu3+ nanorods were synthesized by a hydrothermal method. The SEM
      image indicated the nanorods with diameter of 30-35 nm and length of 200-500 nm.
      The structural stability of Gd2O3:Eu3+ nanorods was investigated by in situ high
      pressure luminescence and Raman spectra up to 18.9 GPa at room temperature. The
      results reveals a pressure-induced phase transition from cubic to hexagonal
      structure at about 11.3 GPa. After releasing pressure, the part of hexagonal
      structure is retained and the other transfers to monoclinic phase.

PMID- 22413316
TI  - Upconversion luminescence enhancement in Yb3+/Tm3+-codoped Lu2O3 nanocrystals
      induced by doping with Li+ ions.
AB  - Lutetium oxide (Lu2O3) nanocrystals doped with 2%Yb3+, 0.5%Tm3+, and various
      doping concentrations of Li+ (0, 3, 5, 7, 10, 12, and 15 mol%) were prepared by
      the sol-gel method. The dependence on different doping concentrations of Li+ ions
      of the structure, morphology, and the upconversion emission intensity of the
      Lu2O3:2%Yb3+, 0.5%Tm3+ nanocrystals was investigated. The obtained Lu2O3
      nanocrystals were systematically characterized by X-ray diffraction (XRD), field
      emission-scanning electron microscopy (FE-SEM), Fourier transformed infrared (FT
      IR) spectra, Raman spectra, and upconversion spectra measurements. It was found
      that all the nanocrystals can be readily indexed to pure cubic phase of Lu2O3,
      indicating good crystallinity. The experimental results show that Li+ doping in
      Lu2O3:2%Yb3+, 0.5%Tm3+ nanocrystals can greatly enhance the upconversion emission
      intensity. The strong blue (490 nm) and the weak red (653 nm) emissions from the
      prepared nanocrystals were observed under 980 nm laser excitation, and attributed
      to the 1G4 --> 3H6 and 1G4 --> 3F4 transitions of Tm3+ ions, respectively. An
      simple analysis based on steady-state rate equations and a power-dependent study
      both indicate that the 1G4 levels can be populated by three-step energy transfer
      (ET) processes. The enhancement of the upconversion luminescence was suggested to
      be the consequence of the modification of the local field symmetry around the
      Tm3+ ion, reduced number of OH- groups, and the enlarged nanocrystal size induced
      by the Li+ ions.

PMID- 22413317
TI  - Optical high temperature sensor based on enhanced green upconversion emissions in
      Er3+-Yb3+-Li+ codoped TiO2 powders.
AB  - The Er3+-Yb3+-Li+ codoped TiO2 powders have been prepared by sol-gel method. The
      strong enhancement of green and red upconversion emissions were obtained for Er3+
      Yb3+ codoped TiO2 by additional Li+ codoping and investigated using 976 nm
      semiconductor laser diode excitation. The enhanced upconversion emissions by the
      addition of Li+ resulted from the formation of Li compound with lower crystal
      field symmetry. The fluorescence intensity ratio (FIR) of green upconversion
      emissions from the transitions of 2H(11/2) --> 4I(15/2) and 4S(3/2) --> 4I(15/2)
      of Er3+ in the Er3+-Yb3+-Li+ codoped TiO2 has been studied as a function of
      temperature in the range of 300-925 K, and the maximum sensitivity was determined
      to be 0.0025 K(-1). Er3+-Yb3+-Li+ codoped TiO2 material with the highest
      operating temperature up to 925 K, has higher temperature sensitivity and
      fluorescence efficiency being a promising candidate for applications in optical
      high temperature sensor.

PMID- 22413318
TI  - The sol-gel process synthesis of GdAl3(BO3)4:Eu3+ nanophosphors.
AB  - GdAl3(BO3)4:Eu3+ red phosphors were prepared using citric acid as complex agent
      by sol-gel technique. The preparation conditions of the precursor synthesis,
      including crystallization temperature and crystallization time were investigated.
      Their structure and luminescence properties were characterized by X-ray
      diffraction (XRD) analysis and fluorescence spectrometry. The results showed that
      GdAl3(BO3)4:Eu3+ phosphor crystallized at 960 degrees C for 2 h have been
      synthesized by sol-gel method. The phosphor is distributed into hexagonal system
      and the lattice parameters are a = 9.2992 nm c = 7.2577 nm. The excitation
      spectrum of Gd(0.95)Al3(BO3)4:Eu(0.05)3+ samples is complex and the frequency
      scale is wide. It consists of a number of main excitation transitions namely
      8S(7/2) --> 6IJ (270 nm) of Gd3+, and the others 7F0 --> 5L6 (400 nm), 7F0 -->
      5D2 (472 nm) and 7F0 --> 5D1 (542 nm) of Eu3+. The main emission peaks are 614 nm
      and 619 nm, which are the characteristic emission peaks of Eu3+. These emission
      peaks correspond to the transition from 5D0 to 7F2 of Eu3+. The shape and the
      wavelength range of the emission spectrum are similar when the sample was excited
      by different excitation spectrum. Only the relative intensity of the emission
      peaks is different from each other.

PMID- 22413319
TI  - Study on luminescence behavior of BaAl12O19:Tb, Eu.
AB  - BaAl12O19:Tb, Eu phosphors were prepared by sol-gel technique. The luminescence
      properties and the energy transfer between Eu2+ and Tb3+ were investigated. For
      BaAll2O19:Tb phosphor, the strongest excitation peak and emission peak produced
      from Tb3+ transition of 5D4-7F5 were at 240 nm and at 550 nm respectively, while
      the peak shape was narrow and peak intensity was large. The Eu2+ added in the
      BaAl12O19:Tb induced energy transfer to Tb3+ and different color luminescence
      from blue (400 nm) to green (570 nm) was obtained by changing the ratio of
      Tb3+/Eu2+ with excitation at 240 nm.

PMID- 22413320
TI  - Synthesis of monodisperse NaYF4:Yb, Tm@SiO2 nanoparticles with intense
      ultraviolet upconversion luminescence.
AB  - In this paper, the NaYF4:Yb, Tm upconversion (UC) nanoparticles (NPs) were
      synthesized using a solvothermal approach, and the core-shell structured
      NaYF4:Yb, Tm@SiO2 NPs, coated with a thin layer of SiO2 on the surface of the
      NaYF4:Yb, Tm NPs, were prepared by a typical Stober method. X-ray diffraction
      (XRD), transmission electron microscopy (TEM), and luminescence spectroscopy were
      applied to characterize these samples. The obtained core-shell structured
      NaYF4:Yb, Tm@SiO2 NPs exhibited a perfect spherical morphology with narrow size
      distribution and smooth surfaces. Under 980 nm excitation, NaYF4:Yb, Tm and
      NaYF4:Yb, Tm@SiO2 samples showed intense ultraviolet UC luminescence, which
      originated from the 1D2 --> 3H6, 1I6 --> 3F4 transitions of Tm3+. These NPs have
      great potential for applications as fluorescent labels, imaging probes, optical
      storage, photodynamic therapy (PDT) in deep tissue, and solid-state lasers.

PMID- 22413321
TI  - Synthesis and upconversion luminescence properties of CaF2:Yb3+/Tm3+
      microspheres.
AB  - CaF2:Yb3+/Tm3+ microspheres were synthesized by using a simple hydrothermal
      method. Their structures and morphologies were characterized by X-ray diffraction
      (XRD) and field-effective scanning electron microscopy (FESEM). The microspheres
      were formed from a large number of nanospheres with almost the same diameter
      after annealing. The growth mechanism of the microspheres was discussed. Strong
      ultraviolet (UV) and blue upconversion (UC) emission from the CaF2 microspheres
      was observed under 980 nm excitation. The enhancement of the UV UC emission was
      attributed to the size effect of the nanoscale particles.

PMID- 22413322
TI  - Photoluminescence of CaxSr(1-x) (NbO3)2:Pr3+ (0 < or = x < or = 1) nanophosphors.
AB  - Nanoparticles of CaxSr(1-x) (NbO3)2 doped with Pr3+ have been synthesized by sol
      gel method. Particles have sizes in the range of 50-70 nm. The CaxSr(1-x)
      (NbO3)2:Pr3+ phosphors showed a white emission under the near-ultraviolet
      excitation (254 nm). There is a large photoluminescence enhancement of the
      CaxSr(1-x) (NbO3)2:Pr3+ phosphor samples when added with 0.5% KCl. X-ray
      diffraction (XRD), transmission electron microscope (TEM), photo luminescent (PL)
      analysis were utilized to characterize the CaxSr(1-x) (NbO3)2:Pr+ particles. The
      concentration quenching of the samples was discussed as well. The optical
      concentration and the calcination temperature were 0.8 mol% of Ca2+ and 900
      degrees C for these phosphors, respectively, the possible mechanism was
      discussed. CaxSr(1-x) (NbO3)2:Pr3+ is a promising white phosphor under near
      ultraviolet excitation for various applications.

PMID- 22413323
TI  - A study on formation of titanium oxide nanoribbons.
AB  - The transformation process of nanoribbons produced by the hydrothermal treatment
      in 10 M NaOH solution at 200 degrees C was investigated systematically via
      electron microscopy. Field emission scanning electron microscope (FE-SEM)
      observation showed that the treatment duration had a strong effect on the product
      morphology from the hollow nanotubes to nanoribbons. The details of
      transformation were studied by transmission electron miscroscopy. Some nanotubes
      assembled into clusters and grew into nanowires as the grain to form the
      nanoribbons, whilemost of nanotubes dissolved into the solution again.

PMID- 22413324
TI  - Property evaluation on the spontaneous polarity for nanopowders.
AB  - For the tourmaline fine powders, in view of their low polarized charge density
      and easily occurred neutralization, a new evaluation model on the spontaneous
      polarity was proposed. By adjusting the temperature and applying electric field,
      the polarized charge could be measured. On this basis, a portable evaluation
      device was designed and assembled into four parts: Voltage Input Unit,
      Temperature Control Unit, Sample Loading Unit, and Charge Detection Unit. Using
      the designed device, the property evaluation on the spontaneous polarity of
      tourmaline fine powders was carried out. The spontaneous polarization intensity
      was finally achieved. After experimental verification, the method had the
      characteristics of easy operation and high accuracy.

PMID- 22413325
TI  - Far infrared emission and portable testing device of fine powders.
AB  - In order for industrial and mining enterprises to fast detect the quality of fine
      mineral powders with far infrared emission, a simple testing model was set up
      according to the relationship between the emission intensity of powders and their
      surface temperature. The corresponding testing device was designed and assembled
      into three parts containing Constant Temperature Heating Part, Temperature
      Measuring Part and Sample Loading Part. By using the tourmaline mineral powders
      with far infrared emission as the research object and combining Fourier transform
      infrared spectroscopy, the calibration for the testing device was carried out.
      The results showed that the far infrared emission intensity of the tourmaline
      powders with different mining area and particle size could be judged. The testing
      results exhibited correct values when compared with those from FTIR measurements.

PMID- 22413326
TI  - Luminescence properties of cubic HfO2-Sc2O3:Eu3+ nano-powders.
AB  - The cubic nano-structured HfO2-Sc2O3:Eu3+ were successfully synthesized via a
      combustion process. Phase evolution of the synthesized powders was determined by
      X-ray diffraction measurements. Pure cubic phase of HfO2-Sc2O3 solid solution was
      obtained after being calcined at 800 degrees C for 2 h.The particle size and
      morphology were analyzed by TEM. The luminescence properties were also
      investigated. Photoluminescence spectra of Eu3+ doped HfO2-Sc2O3 nano-powders
      showed red emission at 613 nm which corresponds to the 5D0-7F2 transition of Eu3+
      ion.

PMID- 22413327
TI  - Nanosecond field-induced quenching of the luminescence from Er-doped silicon
      nanocrystals.
AB  - Er-doped Si-rich SiO2 gate oxide layers containing silicon nanocrystals are
      prepared by implantation of Si+ and Er+ into SiO2 thin films. The
      photoluminescence from both Si nanocrystals around 700-850 nm and Er3+ ions at
      1.54 microm is strongly quenched by applying electric field in the Si-rich oxide
      layer. The quenching time and the recovery time of the photoluminescence from Si
      nanocrystals are less than 50 ns under pulsed field modulation. The quenching
      rate of the luminescence increases with increasing the density and reducing the
      size of the silicon nanocrystals. Our results indicate that the fast quenching
      process originates from the quantum confined Stark effect and enhanced exciton
      ionization by carrier tunneling between the silicon nanocrystals under the high
      electric field.

PMID- 22413328
TI  - Characterization and luminescence of Eu3+ ions doped 12CaO 7Al2O3 nanopowders.
AB  - Eu3+ ions doped 12CaO 7Al2O3 (C12A7) powders with different Eu3+ concentrations
      were prepared by sol-gel combined with solid state reaction method. The results
      of XRD and Raman spectra showed that single cubic phase polycrystalline
      C12A7:Eu3+ powders were prepared. The absorption peaks attributed to f-f
      transition of Eu3+ ion can be observed, indicating that Eu3+ had been
      incorporated into C12A7 lattice site. Visible PL peaks around 578, 588, 614 nm
      were ascribed to 5D0 --> 7FJ (J = 0, 1, 2) transitions of Eu3+ under the
      excitation of 488 nm line. The PL of C12A7:Eu3+ showed the strongest emission
      intensity at Eu3+ concentration of 0.5 at%. Two different types of Eu3+ centers
      were identified by the two lines from 5D0 --> 7F0 transition emission. The doping
      mechanism of C12A7:Eu3+ might be attributed to Eu3+ ions substitution for two
      types of Ca2+ lattice sites in C12A7. The temperature dependent PL spectra of Eu
      doped C12A7 were measured in the range from 100 to 300 K under the excitation of
      488 nm laser line. The PL intensities as a function of temperature were well
      fitted by using a unified theoretical model, considering thermal activation and
      nonradiative energy transfer processes.

PMID- 22413329
TI  - Luminescence and energy transfer characteristics of Ce3+- and Tb3+-codoped
      nanoporous 12CaO 7Al2O3 phosphors.
AB  - The novel green-emitting phosphors of 12CaO 7Al2O3:Ce3+ , Tb3+ (C12A7:Ce3+, Tb3+)
      were synthesized by a solid-state reaction. Upon the excitation of Ce3+ at 350
      nm, the C12A7:Ce3+, Tb3+ phosphor shows intense green emissions located at 543 nm
      assigning to 5D4-7F5 transitions of Tb3+ ions, and weak blue emissions centered
      at 434 nm due to the transitions of Ce3+ 5d-4f. The photoluminescence (PL)
      intensity of Ce3+ decrease with increasing Tb3+ concentration, indicating the
      effective energy transfer (ET) occurred from Ce3+ to Tb3+ in C12A7:Ce3+, Tb3+.
      The ET efficiency between Ce3+ and Tb3+ in the optimum composition reaches to
      99%. Based on Dexter's ET theory, we have demonstrated that the efficient ET is a
      resonant type via dipole-dipole mechanism with an energy transfer critical
      distance of 4.02 A. Our results suggested that C12A7:Ce3+, Tb3+ phosphor would be
      a promising green-emitting phosphor for UV-converting white light-emitting
      diodes.

PMID- 22413330
TI  - White luminescence of Dy3+ ions doped 12CaO 7Al2O3 nanopowders under UV light
      excitation.
AB  - 12CaO 7Al2O3:Dy3+ nanopowders were successfully synthesized by the chemical co
      precipitation method. X-ray diffraction result shows that the single 12CaO 7Al2O3
      phase is formed with Dy3+ ions to replace the Ca2+ ions in the host of 12CaO
      7Al2O3. The yellow and blue emissions, attributed to the forced electric dipole
      transition of 4F(9/2) --> 6H(13/2) centered at 571 nm and the magnetic dipole
      transition of 4F(9/2) --> 6H(15/2) centered at 480 nm, respectively, were
      observed. The integrated intensity ratios of yellow to blue increase from 1.63 to
      1.70 with Dy3+ concentration increasing from 0.8 to 2.0% for the as-prepared
      12CaO 7Al2O3:xDy3+ phosphor. The significantly enhanced emission intensities of
      12CaO 7Al2O3:1.0% Dy3+ phosphor annealed at 900 degrees C for 2 hours in vacuum
      ambient could be ascribed to the decrease of OH(-) groups and the change of the
      surface topography. The thermal stability and the Commission International de
      l'Eclairage coordinates were also investigated. All the photoluminescence
      characteristics indicate that Dy3+ ions doped 12CaO 7Al2O3 may be a good
      candidate for the solid state lighting phosphor as well as white light-emitting
      diodes.

PMID- 22413331
TI  - The effects of Mn2+ doping on the luminescence properties of 12CaO 7Al2O:Eu2+
      nanocrystal phosphor.
AB  - The long lasting blue phosphorescence (LLP) and photostimulated luminescence
      (PSL) after ultraviolet light irradiation at room temperature in 12CaO
      7Al2O3:xEu2+, yMn2+ (x = 0, 0.001; y = 0, 0.01) prepared by the chemical co
      precipitation method were observed. It was shown that novel oxide 12CaO
      7Al2O3:Eu2+, Mn2+ (C12A7:Eu2+, Mn2+) with unique nanocage structure can store
      energy when irradiated with 365 nm photons. And photon energy can be subsequently
      released by exposed to 980 nm light. The codopant Mn2+ enhances the intensity of
      the persistent phosphorescence and PSL due to the existence of more shallow and
      new deeper electron traps in C12A7: Eu2+, Mn2+. A model for energy storing and
      recovering and the detailed mechanism of PSL are presented through comparing with
      the luminescence properties of the co-doped C12A7:Eu2+, Mn2+ and C12A7:Eu2+.

PMID- 22413332
TI  - Preparation and luminescence properties of LaMgAl11O19:Eu3+ phosphor powder.
AB  - LaMgAl11O19, is a kind of rare earth aluminate with the hexagonal structure,
      which has been used as a host material for the luminescence of various rare earth
      and magnet-like ions. LaMgAl11O19:Eu3+ phosphors have been prepared through the
      one-pot method. X-ray diffraction (XRD), thermogravimetric and differential
      thermal analysis (TG-DTA) and photoluminescence spectra were used to characterize
      the resulting phosphors. The results of XRD indicated that the phosphors
      crystallized completely at 1,400 degrees C. In LaMgAl11O19:Eu3+ phosphors, the
      Eu3+ shows its characteristic red emission at 615 nm (5D0-7F2) upon excitation
      into 404 nm, with an optimum doping concentration of 15 mol% of La3+ in the host
      lattices.

PMID- 22413333
TI  - In-situ polymerization approach for preparation of rare earth fluoride phosphors
      coated with PAA.
AB  - Up-conversion nanoparticles (UCNPs), which can convert a radiation from a longer
      wavelength to a shorter wavelength, have great potential uses as bio-labels in
      biological detection. However, these NPs usually cannot be used directly unless
      their surfaces are further modified. In this paper, NaYF4:Yb, Er nanoparticles
      (NPs) were coated with poly(acrylic acid) (PAA) by in situ polymerization for the
      first time. Accordingly, NaYF4:Yb, Er/NaYF4 NPs were synthesized before PAA
      coating to avoid the decay of optical intensity. The resulting UCNPs were
      characterized by X-ray diffraction (XRD), transmission electron microscope (TEM),
      Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis
      (TGA), and up-conversion photoluminescence spectrometry. The XRD results
      indicated that the resultant UCNPs exhibited a pure hexagonal phase. The FT-IR
      spectra and TGA curves revealed that these NPs were coated successfully with PAA.
      Meanwhile, the TEM results showed that well-dispersed UCNPs with the best
      morphology and an average size of about 90 nm were obtained with 8.0 wt% acrylic
      acid content (the content percentage in the whole reaction system) at 0 degrees C
      within 130 min. Fluorescence tests showed that the UCNPs had a strong UC
      fluorescence intensity. Settlement tests revealed that PAA-coated NaYF4 UCNPs had
      more favorable dispersion stability than uncoated UCNPs in an aqueous system.
      These functionalized nanocomposites could be used for further bio-conjugation.

PMID- 22413334
TI  - Upconversion luminescence properties of YF3:Yb3+, Er3+ nanoclusters.
AB  - The synthesis, characterization, and spectroscopy of upconverting Yb3+/Er3+
      codoped YF3 rod-like nanoclusters are presented. The YF3 nanoclusters were
      synthesized by a simple hydrothermal method. The clusters structure was
      characterized by X-ray diffraction, scanning electron microscopy and transmission
      electron microscopy. Under 978 nm laser excitation, stronger blue (4F(5/2) -->
      4I(15/2) and 2p(3/2) --> 4I(11/2)) and green (4S(3/2), 2H(11/2) --> 4I(15/2))
      upconversion luminescence were observed at 978 nm. The measured intensity of
      upconversion luminescence was different when pump power changed, which shows that
      the blue and green upconversion luminescence come from three-photon and two
      photon energy transfer processes, respectively.

PMID- 22413335
TI  - Hot electrons and electron-phonon coupling in a cylindrical nanoshell.
AB  - We use a standard model for the low-temperature electron-phonon interaction in
      metals to calculate the rate of thermal energy transfer between electrons and
      acoustic phonons in suspended metallic nanoshells. The electrons are treated as
      three-dimensional and noninteracting, whereas the vibrational modes are that of
      an thin cylindrical elastic shell of radius R with a free surface and thickness
      h. Disorder is neglected. The temperature dependence of the thermal power is
      obtained analytically for this model, and a crossover from the T3 dependence
      expected for one-dimensional phonons to a T3/(1 - v2) + 9gammaT4/[T*(1 -
      v2)(3/2)] dependence is obtained.

PMID- 22413336
TI  - Mechanical analysis of indentation cracking in Al2O3/ZrO2 nanostructured
      laminated ceramics.
AB  - Residual stress is not the only driving force for indentation cracking in
      Al2O3/ZrO2 laminated ceramics. An additional driving force is induced by
      martensitic transformation in the plastic zone beneath the indenter, whereas
      surface residual compressive stress controls the expansion of surface cracks.
      Contributions of the transformation driving force and surface residual stress are
      not considered in the traditional indentation and indentation-strength theory.
      Therefore, fracture toughness value measured by the traditional methods is
      usually lower than the practical one in Al2O3/ZrO2 laminated ceramics. When the
      improved SENB (Single edge notched beam method)-indentation-fracture method from
      Japanese Industrial Standard (No. JIS R 1607-1990) is used to measure fracture
      toughness of Al2O3/ZrO2 laminated ceramics, the value is more reliable.

PMID- 22413337
TI  - The release of hydrogen reaction of graphene modified NaAlH4.
AB  - In this experiment, we prepared a better performance graphene, by using
      butyrolactone and flavanone, promoting the graphite into high quality graphene
      strip. The obtained graphene were used to catalyze the hydrogen released by
      NaAlH4. The result proved that 5 wt% doped butyrolactone treated graphite and 2
      wt% doped flavanone-treated graphite are good catalyst in NaAlH4's decomposition
      process.

PMID- 22413338
TI  - Preparation, characterization, and photoelectric properties of a covalently self
      assembled monolayer of ferrocenyl hemicyanine.
AB  - A monolayer of a ferrocenyl hemicyanine was covalently self-assembled on an
      indium tin oxide (ITO)-coated glass substrate, and was characterized by UV/Vis
      absorption and X-ray photoelectron spectroscopy, and cyclic voltammetry. The
      photoelectrochemical properties and mechanism of photocurrent generation have
      also been studied. This monolayer film was found to exhibit a large anodic
      photocurrent density of 0.13 microA/cm2 with the highest photoelectric yield of
      3.32% under irradiation of white light (730 nm > lambda > 325 nm) at a bias
      potential of +0.4 V versus saturated calomel electrode.

PMID- 22413339
TI  - Photoelectric properties of TiO2-ZrO2 thin films prepared by sol-gel method.
AB  - Acidic sols of TiO2, ZrO2 and Ti-Zr mixed oxide precursors were prepared. The
      sols were then smeared on quartz substrate and annealed at 650 degrees C for 2
      hour to form polycrystalline oxide films. XRD, SEM, UV-visible absorption spectra
      and XPS were carried out to characterize the films. It was found that the
      crystalline phase of pure titania is an anatase and pure zirconia is a
      tetragonal. The binary oxides show the anatase phase at the molar ratio of Ti:Zr
      = 2.73:1, which means that solid solution was formed. The absorption edge of the
      TiO2-ZrO2 binary oxides showed obvious blue shift as the Zr ratio increased. The
      results obtained indicate that the band gap of the binary oxides could be
      adjusted from 3.2 eV (TiO2) to 7.8 eV (ZrO2) by varying the molar ratio of Ti and
      Zr. Au interdigitated electrodes were produced by planar technology and MSM
      (metal-semiconductor-metal) structure UV detector based on TiO2-ZrO2 binary
      oxides was fabricated. Obvious photoelectric response was observed.

PMID- 22413340
TI  - Halloysite clay nanotubes for controlled release of protective agents.
AB  - Halloysite is a naturally occurring clay mineral with submicron sized hollow
      cylindrical morphology. Halloysite morphology, structure and properties were
      characterized by using SEM, TEM, XRD, FT-IR spectroscopy, surface electrokinetic
      (zeta) potential and nitrogen adsorption isotherms. Comparison of the halloysite
      structure with imogolite was also provided. Halloysite toxicological studies
      revealed that it is environmentally friendly and biocompatible material. Due to
      its unique tubular shape and availability in thousands of tons halloysite has
      potential to be applied as nanocontainers for encapsulation of chemically and
      biologically active agents such as medicines, pharmaceuticals, antiseptics,
      corrosion inhibitors, antifouling agents, and doped with them plastics producing
      smart polymeric nanocomposites with improved mechanical strength. Finally
      possibility to synthesize metal nanorods within the halloysite lumen was
      demonstrated.

PMID- 22413341
TI  - Enhanced performance of P3HT/TiO2 bilayer heterojunction photovoltaic device
      having gold nanoparticles in the donor layer.
AB  - The photovoltaic effects of blending gold nanoparticles (AuNPs) into the donor
      layer of a poly(3-hexylthiophene) (P3HT)/TiO2 bilayer heterojunction device have
      been studied. P3HT was synthesized via the modified Gragnard metathesis method
      and AuNPs with sizes ranging from 12 to 15 nm were formed via a reduction of
      HAuCl4. The blending of AuNPs into P3HT caused a lower photoluminescence (PL)
      intensities and a decreased energy level of the highest occupied molecular
      orbital (HOMO) than the pristine P3HT owing to the good electron-accepting nature
      of AuNPs. Upon the use of P3HT-AuNPs as the donor layer, the decreased
      HOMO(donor) resulted in an increased open circuit voltage (V(OC)) and thus
      enabled the fabricated (P3HT-AuNPs)/TiO2 bilayer heterojunction photovoltaic
      device to have an improved power conversion efficiency of solar energy. V(OC) as
      well as the overall power conversion efficiency increased with an increase in the
      AuNP content as a result of additional interfaces which facilitated the charge
      separation of excitons and percolation pathways which enhanced the electron
      transfer to the TiO2 acceptor. Furthermore, unannealed P3HT-AuNPs exhibited
      nanoholes and provided photovoltaic devices a power conversion efficiency nearly
      two time higher than annealed P3HT-AuNPs.

PMID- 22413342
TI  - Growth of carbon nanostructures using a Pd-based catalyst.
AB  - Carbon nanostructures were synthesized by decomposition of different carbon
      sources over an alumina supported palladium catalyst via Chemical Vapor
      Deposition (CVD). Several experimental conditions were varied to verify their
      influence in the synthesis products: temperature ramping rate, pre-annealing
      conditions, hydrogen pre-treatment, synthesis temperature and time, together with
      the use of different carbon sources. Depending on the experimental conditions
      carbon nanotubes and nanofibers with different shapes and structural
      characteristics were obtained. Straight, coiled and branched morphologies are the
      most common. Among our findings, the addition of hydrogen plays a significant
      role in the structure of the carbonaceous products. For example, the
      decomposition of acetylene on palladium catalysts at 800 degrees C in the absence
      of hydrogen produces only carbon micro- spheres as synthesis products. The
      incorporation of increasing amounts of hydrogen modifies the outcome, from thick
      fibers to carbon nanotubes. To verify the level of graphitization of the
      synthesis products we have used high resolution transmission electron microscopy
      (HRTEM) in addition to Raman spectroscopy. Our results, based on these
      complementary techniques, indicate the decomposition of acetylene on a palladium
      based catalyst, produces the best degree of graphitization in carbon nanotubes
      for a temperature of 800 degrees C and 100 cc/min of hydrogen flow. Similar
      hydrogen flows on the same catalyst, produced highly graphitized nanofibers by
      the decomposition of methane at 850 degrees C.

PMID- 22413343
TI  - Controlling diameter distribution of catalyst nanoparticles in arc discharge.
AB  - It is demonstrated that the diameter distribution of catalyst nanoparticles in
      arc discharge can be controlled by a magnetic field. The magnetic field affects
      the arc shape, shortens the diffusing time of the catalyst nanoparticles through
      the nucleation zone, and consequentially reduces the average diameters of
      nanoparticles. The average diameter is reduced from about 7.5 nm without magnetic
      field to about 5 nm is the case of a magnetic field. Decrease of the catalyst
      nanoparticle diameter with magnetic field correlates well with decrease in the
      single-wall carbon nanotube and their bundles diameters.

PMID- 22413344
TI  - Study of the activity of Grubbs catalyst-functionalized multiwalled carbon
      nanotubes in the ring opening metathesis polymerization.
AB  - The synthesis of polynorbornene by ring opening metathesis polymerization (ROMP),
      in the presence of 1st and 2nd generation Grubbs catalyst-functionalized
      multiwalled carbon nanotubes (MWCNT), has been studied. MWCNTs were obtained by
      catalytic chemical vapour deposition (CCVD) of ethylene. A full characterization
      of the 1st and 2nd generation Grubbs catalyst-functionalized nanotubes was
      performed by FTIR and TG-DTG-MS. The amount of catalyst grafted to the nanotube
      surface was estimated. The activity of the catalyst-functionalized nanotubes in
      ROMP of 2-norbornene was found to be similar to that of bare 1st and 2nd
      generation Grubbs catalysts. The characterization of polynorbornene-carbon
      nanotube composites shows that the nanotubes are well dispersed in the polymer
      matrix.

PMID- 22413345
TI  - Fabrication and enhanced visible light photocatalytic activity of fluorine doped
      TiO2 by loaded with Ag.
AB  - F-doped TiO2 loaded with Ag (Ag/F-TiO2) was prepared by sol-gel process combined
      with photoreduction method. The physical and chemical properties of the prepared
      samples were characterized by X-ray diffraction (XRD), transmission electron
      microscope (TEM), high-resolution transmission electron microscope (HRTEM), UV
      Vis diffuse reflectance spectroscopy (DRS), X-ray photoelectron spectroscopy
      (XPS) and photoluminescence (PL). XPS analysis indicated Ag species existed as
      Ag0 in the structure of Ag/F-TiO2 samples. UV-Vis diffuse reflectance spectra
      showed that the light absorption of Ag/F-TiO2 in the visible region had a
      significant enhancement compared with the F-doped TiO2 (F-TiO2). PL analysis
      indicated that the electron-hole recombination rate had been effectively
      inhibited when Ag loaded on the surface of F-TiO2. The photocatalytic activities
      of the samples were evaluated for the degradation of X-3B (Reactive Brilliant Red
      dye, C.I. reactive red 2) under visible light (lambda > 420 nm) irradiation.
      Compared with F-TiO2, the sample of 0.50 Ag/F-TiO2 showed the highest
      photocatalytic activity. The interaction between F species and metallic Ag was
      responsible for improving the visible light photocatalytic activity.

PMID- 22413346
TI  - Surface morphology changes of graphene on flexible PET substrate upon thermal
      annealing.
AB  - The performance of a polymer photovoltaic device using multilayered graphene on
      an amorphous PET substrate as the electrode was studied. The changes in surface
      morphology of graphene coated polyethylene terephthalate (PETG) substrate upon
      thermal annealing were investigated by atomic force microscopy (AFM), field
      emission scanning electron microscope (FE-SEM) and current-voltage
      characteristics. The root mean square (RMS) roughness of PETG substrate before
      annealing was 36.5 nm that decreased to 11.5 nm after 10 min thermal annealing at
      110 degrees C. The mean grain size of the substrate decreased from 2301 nm2 to
      848 nm2. The PETG surface became smooth when thermally annealed as the voids
      created by the bubbles in the graphene layer were filled up with thermal
      expansion of the PET substrate. However, cracks present initially on the graphene
      due to surface stress between the graphene and PET layer grew further upon
      annealing that deteriorated the device performance. This study on the graphene
      surface morphology change upon annealing and the consequent drop in device
      performance vis-a-vis an ITO glass electrode shows potential drawback of solar
      cell device fabrication on such flexible substrates.

PMID- 22413347
TI  - Production of reduced graphene oxide by UV irradiation.
AB  - Herein, we report on a self-photocatalytic reduction (SPCR) strategy toward the
      production of reduced graphene oxide (GO), carried out by UV irradiation of GO
      dispersion in the presence of N,N-dimethylformamide (DMF) serving as an electron
      donor (ED). It is found that a stable dispersion of rGO is produced by UV
      irradiation of GO solution in the presence of DMF. The use of natural sunlight as
      driving force for such SPCR reaction is also demonstrated.

PMID- 22413348
TI  - Reduction of graphene oxide by thiourea.
AB  - Various compounds with sulfur or diamine structure have been served as efficient
      reducing agents to convert graphene oxide to reduced graphene oxide. In this
      work, we used thiourea with both sulfur and diamine structure to synthesize
      reduced graphene oxide by the general wet chemical reduction method. The
      effective deoxygenation of graphene oxide was confirmed by Fourier transform
      infrared spectroscopy, X-ray photoelectron spectroscopy analysis and Raman
      spectroscopy. The as-prepared reduced graphene oxide is consisted of few-layered
      (no more than seven) and over 60% single-layered graphene sheet determined by
      atomic force microscopy and transmission electron microscopy. It also exhibits
      good dispersion in organic solvents such as ethanol and N,N-dimethylformamide,
      which is useful for the further modification of graphene and preparation of novel
      nanocomposites. This newly found reducing agent is of low toxicity and
      nonvolatile, which makes the reduction much safer.

PMID- 22413349
TI  - Silicon precipitation via photoinduced reaction using femtosecond laser.
AB  - Silicon precipitation inside a glass is an important technique for silicon
      photonics. We successfully precipitated silicon inside silicate glasses
      containing an Al metal film using femtosecond laser irradiation. First, the Al
      inserted sandwiched glass was fabricated by the direct bonding method. The
      results of a tensile test indicated that the adhesive strength of the sandwich
      structure reached approximately 4 MPa. Next, femtosecond laser pulses were
      focused at the Al/glass interface in the sandwich structure. A transmission
      electron microscopy photograph at the focus of the laser showed that the Al
      particles were dispersed into the glass substrate to a depth of approximately 2
      microm from the initial Al layer. In addition, Raman spectra indicated that
      silicon had formed at the interface between the glass and Al film after the laser
      irradiation. The morphology or the particle size of the precipitated silicon was
      successfully modified by changing the repetition rate or the pulse energy of the
      laser.

PMID- 22413350
TI  - Synthesis of alkyl sulfonated fullerenes without catalyst: improved water
      solubility by the sulfonate groups.
AB  - Two new alkyl sulfonated fullerene (C60) derivatives
      C60(O)14(OH)4(OCH2CH2CH2SO3Na)5 (2), C60(O)15(OSO3Na)5(OCH2CH2CH2SO3Na)6 (4) with
      high water-solubility were synthesized by different routes. One derivative (4)
      was facilely synthesized from a sulfonated C60 derivative C60(O)11(OH)4(OSO3Na)8
      (3) in aqueous phase without the addition of any catalyst and has the highest
      water solubility (118 mg/mL) and smallest aggregation size (49.2 nm) in neutral
      aqueous solution (0.1 wt%). Derivative 2 was synthesized from fullerenol
      C60(O)8(OH)13 (1) directly in DMF affording enhanced water solubility compared to
      1. The estimated average molecular formulae of these new alkyl sulfonated C60
      derivatives were determined by XPS spectroscopy and confirmed by FTIR and 1H NMR
      spectroscopies. The measured water solubility of the sulfonated C60 derivatives
      follows the order of 3 < 2 < 4, suggesting that the larger number of functional
      groups is directly correlated to the higher water solubility, and the sulfonate
      groups can improve the water solubility greatly. The aggregation size of 2-4
      measured by dynamic light scattering (DLS) is all smaller than that of fullerenol
      1, indicating that more functional groups result in the improvement of the
      dispersion of fullerenol in water. ESR study indicates that 2-4 have the ability
      to produce stable radicals, and the intensity of the ESR signal decreases
      evidently with the increase of the number of functional groups from 3 to 2 to 4.

PMID- 22413351
TI  - The interaction of serum proteins with carbon nanotubes depend on the
      physicochemical properties of nanotubes.
AB  - With more and more potential applications of carbon nanotubes (CNTs) in different
      fields, the risk of exposure to CNTs is increasing. The interaction between CNTs
      and protein in biological media can affect the way cells interact with, recognize
      and process the nanoparticles, and this has important implications for safety
      considerations. In this study, the interaction of single-walled and multiwall
      CNTs with various serum proteins was investigated. The adsorption kinetics of
      protein to CNTs was investigated and a semi-qualitative analysis was provided by
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Matrix
      assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF
      MS) was used to identify the protein species binding to CNTs and atomic force
      microscopy (AFM) was used to vividly demonstrate the adsorption model of protein
      on CNTs. All the experimental results showed that the adsorption capacity of CNTs
      for protein was highly dependent on the type, arrangement model, size and surface
      modification of CNTs. Significant quantity of proteins in serum could be quickly
      adsorbed by CNTs, mainly including albumin, prealbumin, transferrin, and
      immunoglobulin. Noncovalent functionalization of CNTs by polyethylene glycol
      (PEG) could decrease the protein adsorption on CNTs. These results provide
      crucial insights into human serum proteins binding to different kinds of CNTs,
      which is important for understanding the safe application of carbon nanotubes.

PMID- 22413352
TI  - Derivatization and functionalization of molecular matrix by hydrogen bond at
      liquid-solid interface.
AB  - Derivatization of porous molecular network formed by 1,3,5-tris (10
      carboxydecyloxy) benzene (TCDB) via hydrogen bond interaction is demonstrated in
      this work. With the introduction of 4,4'-bipyridyl (Bpy) the TCDB network is
      observed to form a heteromolecular cluster, TCDB6-Bpy6, on highly oriented
      pyrolytic graphite (HOPG) surface under ambient conditions using scanning
      tunneling microscopy (STM). The derivatized network is further observed to
      accommodate single guest species such as coronene to form a well-ordered ternary
      two-dimensional (2D) structure.

PMID- 22413353
TI  - Nanoporous graphene oxide thin films from nanohybrid multilayers.
AB  - We report on the preparation and characterization study of new nanoporous reduced
      graphene oxide (rGO) film fabricated from electrostatic layer-by-layer assembly
      of gold nanoparticles (gold-NPs) and rGO. Well distributed gold-NPs in multilayer
      film means that the gold-NPs can be readily dissolved by the addition of cyanide
      ions, which allows for a direct and precise comparison of the porosity of
      multilayer thin films based on rGO under the presence and absence of the gold
      NPs. In addition, the LbL assembly methods offers the big advantages of
      possibilities in mass production and 2-dimensional nano-objects based film
      prepared from large size substrates. We expect that this demonstration offers a
      new route to introduce nanopore into multilayer thin films and opens up the
      possibility of building more complex functional multicomponent nanoporous
      structure consisting of 2-dimensional nano-objects, which are believed to be
      useful for nanodevice systems.

PMID- 22413354
TI  - Preparation and field-emission of TaSe2 nanobelt quasi-arrays, and electrical
      transport of its individual nanobelt.
AB  - 3R-TaSe2 nanobelt quasi-arrays were gown on a Ta foil by a facile two-step
      method, namely, firstly the TaSe3 nanobelt arrays were grown on a Ta foil by a
      surface-assisted chemical vapor transport, and then they were pyrolyzed to 3R
      TaSe2 nanobelt quasi-arrays in vacuum. The nanobelts have low work function and
      the Ta foil has high conductivity, so the nanobelt arrays possess good electronic
      field emission performance with a low turn-on (3.6 V/microm) and threshold fields
      (4.3 V/microm) (which are defined as the macroscopic field required to produce a
      current density of 10 microA/cm2 and 1 mA/cm2, respectively) and a high
      enhancement factor (1045) at an emission distance of 200 microm. The electric
      transport of the individual nanobelt reveals that it is a high-conductive
      semiconductor, and observed by the variable-range hopping model. It suggests that
      the nanobelts have potential applications in field emission and field effect
      transistors.

PMID- 22413355
TI  - Antireflective hydrophobic si subwavelength structures using thermally dewetted
      Ni/SiO2 nanomask patterns.
AB  - We report the disordered silicon (Si) subwavelength structures (SWSs), which are
      fabricated with the use of inductively coupled plasma (ICP) etching in SiCl4 gas
      using nickel/silicon dioxide (Ni/SiO2) nanopattens as the etch mask, on Si
      substrates by varying the etching parameters for broadband antireflective and
      self-cleaning surfaces. For the fabricated Si SWSs, the antireflection
      characteristics are experimentally investigated and a theoretical analysis is
      made based on the rigorous coupled-wave analysis method. The desirable dot-like
      Ni nanoparticles on SiO2/Si substrates are formed by the thermal dewetting
      process of Ni films at 900 degrees C. The truncated cone shaped Si SWS with a
      high average height of 790 +/- 23 nm, which is fabricated by ICP etching with 5
      sccm SiCl4 at 50 W RF power with additional 200 W ICP power under 10 mTorr
      process pressure, exhibits a low average reflectance of approximately 5% over a
      wide wavelength range of 450-1050 nm. The water contact angle of 110 degrees is
      obtained, indicating a hydrophobic surface. The calculated reflectance results
      are also reasonably consistent with the experimental data.

PMID- 22413356
TI  - Characterization of stoichiometric nanocrystalline spinel ferrites dispersed on
      porous silica aerogel.
AB  - Stoichiometric magnetic nanosized ferrites MFe2O4 (M = Mn, Co, Ni) were prepared
      in form of nearly spherical nanocrystals supported on a highly porous silica
      aerogel matrix, by a sol-gel procedure. X-ray diffraction and transmission
      electron microscopy indicate that these materials are made out of non
      agglomerated ferrite nanocrystals having size in the 5-10 nm range. Investigation
      by Mossbauer Spectroscopy was used to gain insights on the superparamagnetic
      relaxation and on the inversion degree. Magnetic ordering at room temperature
      varies from superparamagnetic in the NiFe2O4 sample, highly blocked
      (approximately 70%) in the MnFe2O4 sample and nearly fully blocked in the CoFe2O4
      sample. A fitting procedure of the Mossbauer data has been used in order to
      resolve the spectrum into the tetrahedral and octahedral components; in this way,
      an inversion degree of 0.68 (very close to bulk values) was obtained for 6 nm
      silica-supported CoFe2O4 nanocrystals.

PMID- 22413357
TI  - The cytotoxicity of NiO nanoparticle with borate capping.
AB  - The impact of surface capping on cytotoxicity of NiO nanoparticle was
      investigated with Escherichia coil (E.coli) in this work. The NiO nanoparticle
      and NiO nanoparticle capped by borate (denoted as NiO-borate) were synthesized by
      hydrothermal method. The average size of both nanoparticles is about 4.0 nm. The
      plate experiments demonstrated that NiO-borate nanoparticles show lower
      cytotoxicity than NiO nanopaticles. Further spectrophotometric analysis revealed
      that the concentration of both extracellular and intercellular Ni2+ in NiO-borate
      system were lower than that of uncapped one. Intracellular ICP-AES analysis also
      showed the concentration of Ni element was higher than Ni2+, suggesting the NiO
      nanoparticles might penetrate into the cellular interior. Comprehensive AFM, SEM
      and TEM observation illustrated both NiO-borate and NiO nanoparticles lead to the
      collapse of cellular body, the convex on the cell wall and the damage of cell
      wall ultimately. In summary, the surface capping with borate on NiO nanopaticles
      will suppress the release of the Ni2+ ions and impede the contact between the NiO
      nanoparticle and cell wall, which ultimately decreased the cytotoxicity of NiO
      nanoparticles.

PMID- 22413358
TI  - Fabrication of gold nanoparticle assembled polyurethane microsphere template in
      trypsin immobilization.
AB  - The separation, reusability and high catalytic activity of bioconjugate remain
      challenging task in proteins bound gold nanoparticles. A facile synthetic route
      for the fabrication of gold nanoparticle assembled polyurethane microsphere
      template and immobilization of trypsin on gold/polyurethane surface to form
      trypsin-nanogold-polyurethane bioconjugate was developed. The bioconjugate was
      characterized by X-ray diffraction, Field emission scanning electron microscopy,
      Transmission electron microscopy, UV-visible, Fourier transform infrared,
      Fluorescence and Circular dichroism spectroscopy. The catalytic studies confirmed
      retention of approximately 40% of its original activity even after eight
      consecutive reaction cycles. The bioconjugate is also very effective for its
      separation from the reaction medium and exhibited significant enhanced stability
      over a wide range of pH and temperature compared to free trypsin. These findings
      clearly demonstrate that trypsin immobilized gold nanoparticle assembled
      polyurethane microsphere acts as an excellent recyclable biocatalyst with enzyme
      specific biocompatibility.

PMID- 22413359
TI  - Fabrication of fluoroalkylsilane modified ZnO nanorod films for electrode
      protection of electrophoretic displays.
AB  - The electrode protection has gained importance because of its positive robust
      role for the long term display quality of electrophoretic displays. A simple
      method of zinc oxide nanorod films prepared by electrochemical deposition and
      coupling with fluoroalkylsilane (FAS) is introduced to fabricate electrode
      protection films for Indium Tin Oxide (ITO) electrodes. The surface
      microstructures of zinc oxide films were characterized by scanning electron
      microscopy, showing a regular nanorods array. After treated by FAS the surface
      showed extremely low surface free energy with a water contact angle of 148.0 +/-
      2.0 degrees. The settlement of pigments was considerably reduced according to the
      reflectance measurement by ultraviolet spectrophotometer. A weight experiment
      further confirmed that 90% of the pigment conglutination was prevented by the
      surface modification. This research can provide an economical approach to improve
      reliability and long-term image quality of the electrophoretic displays.

PMID- 22413360
TI  - Growth of one-dimensional polyindole nanostructures.
AB  - One-dimensional (1D) nanostructured polyindole (Nano-Pind) was synthesized with
      10 minutes (Pind-10 m) and 24 hours (Pind-24 h) of polymerization time using a
      facile chemical oxidative polymerization method. The obtained Nano-Pinds were
      explored to study the differences in their structural, optical, spectral and
      conducting properties with regard to the variation in polymerization duration.
      Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM)
      reveal formation of long and smooth surfaced 1D nanostructures of Pind with
      diameter of approximately 25-125 nm and lengths of several microns. Structural
      chemical analysis of the Nano-Pinds conducted by Fourier Transform Infrared
      (FTIR), Nuclear Magnetic Resonance (NMR) and Fluorescence spectroscopic
      measurements support their formations, thereby indicating Pind-24 h to exhibit
      sharper and far better resolved spectral profile than that of Pind-10 m. The Nano
      Pinds exhibit good blue-light emitting property, and improved Electrical
      Conductivity (EC) than earlier reported globular Pinds, suggesting their
      potential applications in nanotechnology, especially in the field of
      optoelectronics. To the best of our knowledge, this is the first report on 1D
      nanostructures of Pind.

PMID- 22413361
TI  - Preparation and photocatalytic properties of nanometer-sized magnetic
      TiO2/SiO2/CoFe2O4 composites.
AB  - Magnetic TiO2/SiO2/CoFe2O4 nanoparticles (TiO2/SCFs) were prepared by a sol-gel
      process in a reverse microemulsion combined with solvent-thermal technique.
      TiO2/SCFs were characterized by Fourier transform infrared spectrometry,
      thermogravimetric analysis-differential scanning calorimetry, X-ray diffraction,
      Raman spectrometry, TEM, BET specific surface area measurement, and magnetic
      analysis. Structure analyses indicated that TiO2/SCFs presented a core-shell
      structure with TiO2 uniformly coating on SiO2/CoFe2O4 nanomagnets (SCFs) and
      typical ferromagnetic hysteresis. TiO2/SCFs showed larger specific surface area
      and better photocatalytic activities than TiO2 and TiO2/CoFe2O4 photocatalysts
      prepared by the same method. The doping interaction between TiO2 and CoFe2O4
      reduced thanks to the inert SiO2 mesosphere.

PMID- 22413362
TI  - Valence excitations and dopant distribution of Al doped ZnO nanowires analyzed by
      electron energy loss spectroscopy.
AB  - Valence electron energy loss spectroscopy (VEELS) with scanning transmission
      electron microscopy (STEM) has been employed to probe the valence excitations and
      dopant distribution of Al doped ZnO nanowires. The results reveal that while the
      typical Al concentration is on the order of 1020 1/cm3, Al tends to segregate at
      the surface leading to an Al-rich sheath. In VEEL spectra, O-2p, Zn-3d, Al-3p, O
      2s, interband transitions as well as bulk plasmon have been identified. The bulk
      plasmon peak is blue-shifted, and the projected interband transition decreases
      from 2.14 to 1.88 eV as the doping concentration increases from 0.83 x 10(20) to
      2.18 x 10(20) 1/cm3.

PMID- 22413363
TI  - Carboxymethylated dextran-coated magnetic iron oxide nanoparticles for
      regenerable bioseparation.
AB  - Carboxymethylated dextran (CMD)-coated magnetic iron oxide nanoparticles (MNPs)
      were synthesized using a co-precipitation method. Compared to neutral dextran
      coated MNPs, the CMD coating provides good dispersity and colloidal stability to
      the CMD-MNPs. In particular, the carboxyl groups on the CMD can be readily
      activated for covalent attachment of antibody molecules. The superparamagnetic
      property of the antibody-covered CMD-MNPs enables the captured antigen to be
      separated from the sample solution and CMD coating significantly reduces the
      nonspecific binding of the nanoparticles. Regeneration of the anti-BSA antibody
      covered CMD-MNPs with NaOH does not significantly decrease the antibody activity,
      and the repeated magnetic separation and washing steps cause only small loss of
      the starting materials. The method was found to be highly reproducible (RSDs for
      BSA adsorption and desorption are between 0.78% and 5.1%). The anti-BSA antibody
      covered CMD-MNPs possess good selectivity and are able to capture protein
      antigens from real samples.

PMID- 22413364
TI  - Reassembled graphene-platelets encapsulated silicon nanoparticles for Li-ion
      battery anodes.
AB  - Among lithium alloy metals, silicon is an attractive candidate to replace
      commercial graphite anode because silicon possesses about ten times higher
      theoretical energy density than graphite. However, electrically nonconducting
      silicon undergoes a large volume changes during lithiation/delithiation
      reactions, which causes fast loss of storage capacity upon cycling due to
      electrode pulverization. To alleviate these problems, electrodes comprising Si
      nanoparticles (20 nm) and graphene platelets, denoted as SiGP-1 (Si = 35.5 wt%)
      and SiGP-2 (Si = 57.6 wt%), have been prepared with low cost materials and using
      easily scalable solution-dispersion methods. X-ray diffraction (XRD), scanning
      electron microscopy (SEM) and high-resolution transmission electron microscopy
      (HR-TEM) analyses indicated that Si nanoparticles were highly dispersed and
      encapsulated between graphene sheets that stacked into platelets in which
      portions of graphite phases were reconstituted. From the galvanostatic cycling
      test, SiGP-1 exhibited a reversible lithiation capacity of approximately 802
      mAh/g with excellent capacity retention up to 30 cycles at 100 mA/g. Further
      cycling with a step-increase of current density (100-1,000 mA/g) up to 120 cycles
      revealed that it has an appreciable power capability as well, showing 520 mAh/g
      at 1,000 mA/g with capacity loss of 0.2-0.3% per cycle. The improved
      electrochemical performance is attributed to the robust electrical integrity
      provided by flexible graphene sheets that encapsulated dispersed Si nanopraticles
      and stacked into platelets with portions of reconstituted graphite phases in
      their structure.

PMID- 22413365
TI  - Characterization of superparamagnetic iron oxide nanoparticles and its
      application in protein purification.
AB  - The application of surface modified magnetic adsorbent particles in combination
      with magnetic separation techniques has received considerable awareness in recent
      years. There is a particular need in protein purification and analysis for
      specific, functional and generic methods of protein binding on solid supports.
      Nanoscale superparamagnetic iron oxide particles have been used to purify a
      natural coagulant protein extracted from Moringa oleifera seeds.
      Spectrophotometric analysis of the coagulant protein was performed using
      synthetic clay solution as substrate. Protein binding with carboxyl and silica
      surface modified superparamagnetic iron oxide nanoparticles (SPION) were compared
      with the known carboxyl methyl cellulose (CMC) beads of approximately 1 microm.
      SPION modified with carboxyl surface showed higher binding capacity towards the
      coagulant protein compared to the CMC beads. The high surface area to volume
      ratio of the carboxyl-coated SPION resulted in high binding capacity and rapid
      adsorption kinetics of the crude protein extract. The purification and molecular
      weight of coagulant protein is analyzed by SDS-PAGE. This approach utilizes the
      most efficient, feasible and economical method of coagulant protein purification
      and it can also be applicable to other proteins that possess similar properties.

PMID- 22413366
TI  - Fabrication of nanoporous networks with tunable triangular cavities with a
      molecular template.
AB  - Herein we report a systematic construction of highly regular 2D triangular
      nanoporous networks by host-guest interaction. All molecular building blocks have
      the same four carboxylic acids groups, while the lengths of the blocks increase
      from 1.94 nm up to 2.90 nm. By using a suitably designed guest molecule, called
      coronene, we have fabricated steady porous network with tunable size of the edge
      length of the triangular pores of 3.2 nm, 3.7 nm and 4.1 nm at the liquid-solid
      interface. The results clearly demonstrate this approach may be also an efficient
      method to form the porous structures stable and controllable both in shape and in
      size.

PMID- 22413367
TI  - Composites of polyvinyl alcohol and carbon (coils, undoped and nitrogen doped
      multiwalled carbon nanotubes) as ethanol, methanol and toluene vapor sensors.
AB  - We investigate the chemical sensing behavior of composites prepared with
      polyvinyl alcohol and carbon materials (undoped multiwalled carbon nanotubes,
      nitrogen-doped multiwalled carbon nanotubes and carbon nanocoils). We determine
      the sensitivity of thin films of these composites for ethanol, methanol and
      toluene vapor, comparing their conductance and capacitance responses. The
      composite that exhibits highest sensitivity depends on specific vapor, vapor
      concentration and measured electrical response, showing that the interactivity of
      the carbon structure with chemical species depend on structural specificities of
      the carbon structure and doping.

PMID- 22413368
TI  - Synthesis of different architectures like stars, multipods, ellipsoids and spikes
      of zinc oxide by surfactantless precipitation.
AB  - Zinc oxide with different morphologies like stars, multipods, ellipsoids and
      spikes was synthesized using zinc nitrate and sodium hydroxide in the absence of
      surfactants. Seed mediation was found to be essential for the formation of ZnO
      nanospikes. Synthesized ZnO samples were characterized by X-ray diffraction
      (XRD), scanning electron microscopy (SEM), high resolution transmission electron
      microscopy (HRTEM), UV-visible diffuse reflectance spectroscopy (UV-vis-DRS) and
      energy dispersive analysis by X-rays (EDAX) techniques. The predominant c-axis
      growth of hexagonal lattice was observed in ZnO anisotropic particles. TEM
      analysis revealed the formation of two types of ZnO ellipsoid particles.
      Concentration of the reactants was found to have a role in controlling the
      morphology of the resulting ZnO. Mechanism of formation of varying morphologies
      of ZnO particles has been proposed.

PMID- 22413369
TI  - A first-principles study on water flow through single-walled carbon nanotubes
      using artificial neural network method.
AB  - Ab initio molecular dynamics simulations are done to elucidate the electronic
      structure and properties of water/single-walled carbon nanotubes (SWCNTs)
      systems. The artificial neural network (ANN) approach and statistical methods are
      then used to model and analyze these properties. The ANN method substantially
      speeds up the ab initio electronic structure calculations and has superior
      accuracy in mimicking the results of such calculations. We aim to understand the
      effects of CNT chirality, temperature, and CNT flexibility on the water diffusion
      inside SWCNTs. In this regard, the CNT is fixed implies that the position of CNT
      is kept constant during the diffusion process. Statistical analysis of results
      shows that there is a nonmonotonic variation of diffusion length of water with
      respect to the CNT chirality. However, an increase in temperature and rigid CNTs
      accelerate the water diffusion.

PMID- 22413370
TI  - Fabrication of luminescent silver doped PbS nanowires in polymer.
AB  - We report here fabrication of silver (0 to 1.76 mol%) doped PbS nanowires (radius
      r approximately 1.75 nm) in polymer by a simple wet chemical process. An X-ray
      photoelectron spectroscopy study clearly confirms the possibility of silver (Ag)
      doping in PbS nanowires. Both absorption and photoluminescence spectra reveal
      very strong quantum confinement effect in PbS nanowires as expected for a r/Bohr
      radius ratio approximately 0.0972 nm. Visible excitonic emission is observed at
      room temperature in the photoluminescence spectra of undoped and silver doped PbS
      nanowires in polymer. The excitonic emission is appreciably blue-shifted when
      doped by silver (1.76 mol%) indicating strong modification of the electronic
      states by magnetic silver ions. While Ag2+ centers at the substitutional lattice
      site show an emission band around 525 nm, Ag0 at the interstitial site act as
      nonradiative recombination centers. Effect of silver doping on the luminescence
      intensity is also discussed.

PMID- 22413371
TI  - Preparation, characterization and formation mechanism of thermoplastic
      polyurethane nanostructures using solution wetting template.
AB  - Template wetting with polymer solutions has not been well understood up to now,
      and the formation mechanism of polymer nanostructures with this method is still
      to be revealed. In the present work, thermoplastic polyurethane (TPU)
      nanostructures were prepared by wetting cylindrical nanopores in an anodic
      aluminum oxide (AAO) membrane with TPU solution in dimethylformamide (DMF)
      followed by solvent evaporation. Both tubular structures and solid structures
      were simultaneously observed at four different concentrations of TPU solutions
      (i.e., 5, 7, 10, and 15 wt%) by a scanning electron microscope (SEM) and a
      transmission electron microscope (TEM). Furthermore, a transition from a tubular
      structure to a solid structure was also found at a higher concentration of TPU
      solution (15 wt%). It is speculated that the top part of the single nanostructure
      is tubular, and the lower part is solid. A "capillary wetting-evaporation
      deposition" mechanism is given to explain such a phenomenon. According to this
      mechanism, the higher polymer concentration, the larger amount of solution, and
      the smaller pore size are believed to be beneficial for the formation of solid
      structures.

PMID- 22413372
TI  - Hydrothermal synthesis and luminescence properties of multiform lanthanide ions
      doped YVO4 architectures.
AB  - YVO4 flowerlike architectures with well-aligned microneedles and urchin-like
      architectures with nanorods have been synthesized using a facile hydrothermal
      method in the presence of disodium ethylenediamine tetraacetate (Na2H2L). The
      morphology of the YVO4 flowerlike architectures can be easily controlled by
      adjusting the pH value of the reaction system. Proper reaction temperature and
      the basic source ammonia are key requirements for the fabrication of the
      flowerlike architectures. The additive Na2H2L can coordinate with metal ions to
      form strong complexes and be absorbed on specific crystal surfaces of the initial
      colloidal precipitates, which serve as seeds for the anisotropic growth. The
      formation mechanism for the YVO4 assemblies has been discussed on the basis of
      time-dependent experiments. YVO4:Ln3+ (Ln = Eu, Dy and Sm) phosphors preserved
      the architecture morphologies show strong light emissions with different colors
      coming from different activated ions under ultraviolet excitation.

PMID- 22413373
TI  - Pd-Ag alloy dendritic nanowires: fabrication and application in hydrogen sensor.
AB  - Dendritic Pd-Ag alloy nanowires (Pd-Ag DNWs) with different bimetallic
      composition have been directly self-assembled on the microelectrodes from mixed
      solutions of palladium and silver ions by applying an alternating current (AC)
      field. The size and morphology of the final product were controlled via adjusting
      the electrodeposition parameters and the metal ion concentration ratio. The
      influence of three factors on the bimetallic composition in alloy nanowires was
      examined. Structural characterizations suggest that there was a preferential
      growth along (200) and (111) directions, leading to the formation of Pd-Ag
      nanodendritic wires with 150-200 nm in stem and branch diameter. The mechanism of
      forming the DNWs is discussed. The DNWs were studied as sensing materials for the
      detection of hydrogen, and they were found to exhibit good sensitivity and
      reproducibility. The Pd-Ag sensing materials with 22.2 wt% Ag content possessed
      were also found to display a rapid response time of less than 1 min for 4% (V/V)
      hydrogen concentration.

PMID- 22413374
TI  - Characteristics and photo-responsive release property of liposome containing 7
      acetoxy coumarin.
AB  - A photo-responsive liposome was developed by loading 7-acetoxy coumarin (ATC) in
      egg phosphatidylcholine (EPC) liposome. ATC was derivetized from 7-hydroxy
      coumarin using sodium acetate. The ATC-loaded liposomes were prepared by
      suspending the dry mixture film of ATC/EPC in distilled water and sonicating the
      suspension. When the ATC to EPC ratio was less than 1:8, homogeneous liposomal
      suspensions were obtained without any precipitate. On 1H NMR spectra, the
      unsaturated chains of liposomal EPCs were somewhat deteriorated by a subsequent
      irradiation, the irradiation of lambda = 365 nm and then the irradiation of
      lambda = 254 nm. On TEM photos, the size of liposomes incorporating ATC markedly
      increased by the subsequent irradiation. Photo-dimerization (under lambda = 365
      nm) and de-dimerization (under lambda = 254 nm) of ATC took a place even in EPC
      liposomes. Upon the irradiation of lambda = 254 nm, liposome containing ATC
      dimers exhibited an enhanced release of 5(6)-carboxyfluorescein compared with
      liposome containing ATC monomer and liposome free of ATC. The de-dimerization of
      ATC dimers is believed to fluidize the liposomal membrane and promote the
      release.

PMID- 22413375
TI  - Preparation and photocatalytic property of porous CuO hollow microspheres via
      carbon sphere templates.
AB  - Porous copper oxide (CuO) hollow microspheres have been successfully fabricated
      by using carbon spheres as templates. The products were characterized by scanning
      electron microscopy (SEM), X-ray diffractometry (XRD) and Fourier transform
      infrared spectroscopy (FTIR). The influences of different experimental parameters
      on the morphology of CuO structures have been investigated in detail and the
      possible formation mechanism of porous CuO hollow microspheres has also been
      proposed. The specific surface area of the hollow spheres with 74.805 m2/g is
      measured by BET method. Barrett-Joyner-Halenda (BJH) calculations for the pore
      size distribution, derived from desorption data, reveal that the average pore
      radius is 8.56 nm, and the total pore volume (r = 1686.1 A, P/P0 = 0.994296) is
      0.107257 cc/g. UV-vis absorption spectrum shows quantum size effect of porous CuO
      hollow microspheres. Furthermore, the porous CuO hollow microspheres exhibit high
      efficiency for photodegradation of a sample organic dye, Rhodamine B (RhB), under
      UV light.

PMID- 22413376
TI  - Meaningful family engagement.

PMID- 22413377
TI  - Taking child and family rights seriously: family engagement and its evidence in
      child welfare.

PMID- 22413378
TI  - Fostering families' and children's rights to family connections.
AB  - Recent federal legislation strengthens children's and families' rights to family
      centered practice by increasing the responsibility of child welfare agencies to
      identify and engage extended family members in providing care and support to
      children placed out of the home. Preliminary results from an experimental study
      of a federally funded family finding project found greater involvement of family,
      kin, and informal supports and a higher likelihood of reunification or relative
      placement compared with standard child welfare services.

PMID- 22413379
TI  - Perceptions of fidelity to family group decision-making principles: examining the
      impact of race, gender, and relationship.
AB  - This study explored the perceptions of fidelity to family group principles using
      comparative information from family, friends, and professionals, taking into
      account race and gender. White respondents felt there was a greater degree of
      fidelity than did the African American respondents, with other race respondents
      sometimes rating similarly to both white and African American respondents.
      Professionals generally perceived a greater level of fidelity and there were
      significant race by respondent interactions.

PMID- 22413380
TI  - Does community and family engagement enhance permanency for children in foster
      care? Findings from an evaluation of the family-to-family initiative.
AB  - There is limited research assessing the effectiveness of family engagement for
      improving permanency for children. An important challenge is that randomized
      designs are not feasible for evaluating these practices because effective
      implementation of family engagement requires systemic change. Findings from a
      national evaluation are presented to illustrate how preliminary evidence can be
      developed from comprehensive child welfare reform initiatives. The results show
      when and how family and community participation may facilitate permanency for
      children.

PMID- 22413381
TI  - Family engagement in the perinatal period and infant rights.
AB  - The meaning of human rights for children is a contested issue; the notion of
      rights for unborn babies poses additional complexity. Drawing on data from a
      prospective case study of a specialist drug and alcohol obstetric provider and
      the statutory child protection service, this article discusses family engagement
      within a child-rights framework, and demonstrates how adherence to the "best
      interests" principle, in the absence of an appropriate service provision,
      excludes vulnerable mother/infant dyads from drawing on extended family support.

PMID- 22413382
TI  - Two generations at risk: child welfare, institutional boundaries, and family
      violence in grandparent homes.
AB  - Participation of extended family members, particularly custodial grandparents,
      has generally resulted in better outcomes for abused children and relief for an
      overburdened child welfare system. This research explores the risk of adolescent
      perpetrated violence in custodial grandparent households with data from the
      Florida Department of Juvenile Justice. Findings suggest that living arrangements
      with custodial grandparents have a significant and differential impact on rates
      of violent offending for chronic and serious offenders by race and gender.

PMID- 22413383
TI  - Engaging with families in child protection: lessons from practitioner research in
      Scotland.
AB  - This paper reports findings from practitioner-led research on engagement with
      families in the child protection system in Scotland. Engagement is here defined
      in a participative sense, to mean the involvement of family members in shaping
      social work processes. Key findings include the importance of workers building
      trusting relationships; the value of honest and clear communication, information,
      and explanation; and the potential for formal structures such as reports and
      meetings to hinder family engagement. These findings contribute to a growing
      critique of managerialism in social work.

PMID- 22413384
TI  - Multiple family groups: an engaging intervention for child welfare-involved
      families.
AB  - Differences between child welfare- and non-child welfare-involved families
      regarding barriers to child mental health care, attendance, program satisfaction,
      and relationship with facilitators are examined for a multiple family group
      service delivery model aimed at reducing childhood disruptive behaviors. Although
      child welfare-involved caregivers reported more treatment barriers and less
      program satisfaction than non-child-welfare-involved families, no significant
      differences exist between groups on average total sessions attended and
      attendance rates over time.

PMID- 22413385
TI  - Rights and the role of family engagement in child welfare: an international
      treaties perspective on families' rights, parents' rights, and children's rights.
AB  - According to international human rights treaties, what rights do family members,
      parents, and children have in family engagement in child welfare decision-making?
      A socio-legal analytical approach produces a typology of rights, then applies the
      typology to eight countries' approaches to family engagement to show that strong
      bundles of rights are available in some countries, but not in others. This study
      reveals international treaties have articulated many rights necessary to family
      engagement, but some rights are missing.

PMID- 22413386
TI  - Warren White, KOMET USA.

PMID- 22413387
TI  - Dental lab registration: dentists leading the way.

PMID- 22413388
TI  - A Q&A with Kevin McKay of DDS refining.

PMID- 22413389
TI  - Plaque inhibition: the science and application of oral rinses.
AB  - The adjunctive use of therapeutic mouthrinses provides a way of overcoming
      deficiencies in mechanical tooth cleaning. Through direct destruction of
      susceptible oral bacteria or through the prevention of bacterial adhesion and
      aggregation, therapeutic mouthrinses are a well-accepted means of interrupting
      the accumulation and progression of oral biofilms, which in turn may interrupt or
      prevent the progression of gingivitis. Therefore, therapeutic mouthrinses play an
      important role in the treatment and prevention of gum disease and in the
      maintenance of oral health.

PMID- 22413390
TI  - The future: materials, challenges in dentistry, and education. Interview by Dr.
      Damon Adams.

PMID- 22413391
TI  - Dentistry in the digital age: an update.

PMID- 22413392
TI  - Bioceramics, Part 2: The clinician's viewpoint.

PMID- 22413393
TI  - Case report: an implant resolution to idiopathic pain.

PMID- 22413394
TI  - Effective denture stabilization in an atrophic mandible.

PMID- 22413395
TI  - "The mother of all black triangles" case.
AB  - Before the Bioclear matrix and a disciplined approach to composite treatment of
      black triangles, many treatments ended with significant compromise in periodontal
      health. Many cases debonded soon after placement. Others suffered problems with
      stain. Nonetheless, our patients are hopeful for a better solution. The
      interdental papilla serves as both a functional and aesthetic asset. Anatomically
      ideal interproximal composite shapes that are mirror smooth can serve as a
      predictable scaffold to regain this valuable gingival architecture. Clean enamel
      surfaces can be leveraged to permanently retain the restorations. However, the
      reader is cautioned that to attempt this elective procedure using no
      magnification, without a strict adherence to dentin detoxification with a
      blasting appliance, and using a flat matrix, nontreatment or referral is
      recommended. Our profession can change its thought processes, retrain its hands
      and expand its armamentarium to perform techniques that were previously
      impossible.

PMID- 22413396
TI  - Bioesthetic dentistry , Part 2.

PMID- 22413397
TI  - Aesthetic rehabilitation.

PMID- 22413398
TI  - Multidisciplinary rehabilitation: tunnel grafting techniques.

PMID- 22413399
TI  - General dentistry as a specialty.

PMID- 22413400
TI  - Ringing the changes.

PMID- 22413401
TI  - Palliative care in the community: the complexity of service provision.

PMID- 22413402
TI  - Skin care in the older person: identifying and managing eczema.
AB  - Eczema is a common skin condition in older people. Eczema is a long-term
      condition and older people may have had atopic eczema for many years; it may also
      be an acute condition, caused by a drug reaction. Many older people experience
      eczema and dermatitis for the first time as a consequence of ageing skin or
      triggered by environmental factors. Community nurses need to be able to assess
      older people's skin and recognize any signs and symptoms of eczema to ensure
      prompt treatment and good ongoing skin care.

PMID- 22413403
TI  - A literature review of two laxatives: lactulose and polyethylene glycol.
AB  - This paper presents a literature review of two commonly used osmotic laxatives,
      lactulose and polyethylene glycol (PEG). With increasing numbers of nurses in the
      community being non-medical prescribers, informed decisions on choice of
      laxatives is required. Nurses who do not prescribe will often have a view for the
      benefit of their patients. Following a literature search, eight papers were
      selected for review. The review leads to the conclusion that, while both
      preparations are useful, PEG is more effective in many instances and should be
      the laxative of choice unless there are contraindications arising from the
      assessment of the patient. Non-pharmacological approaches to the management of
      constipation should be addressed before considering laxative use.

PMID- 22413404
TI  - Xerosis of the feet: a comparative study on the effectiveness of two
      moisturizers.
AB  - The treatment for xerosis (dry skin) is the repeated use of moisturizers to
      hydrate the skin. Their use is based on sound evidence of the importance of
      maintaining the skin's water content. Although the skin on the plantar surface of
      the foot is very thick, it is highly visco-elastic and copes with high levels of
      frictional, compressive and shear stresses applied to it by being supple and well
      hydrated. Problems arise when the skin becomes dry and loses its elastic
      properties. Fissures can occur which are often painful and can act as portals for
      infection. This article describes a double-blind clinical study to evaluate and
      compare the effectiveness of two commonly used moisturizers and to see if one was
      significantly better than the other at hydrating the skin of the feet. The two
      creams used were Aqueous Cream BP and CCS Foot Care Cream. Skin hydration levels
      were measured before any application of moisturizer and again after two weeks of
      twice daily application. Results showed that the regular use of both moisturizers
      had a significant hydrating effect on the skin. However, CCS Foot Care Cream had
      a significantly greater hydrating effect than Aqueous Cream BP.

PMID- 22413406
TI  - Nurses' knowledge of the provision of oral care for patients with dysphagia.
AB  - There has been little research on the provision and adaptation of oral care for
      patients with dysphagia in nursing homes. This study collected data via a
      questionnaire specifically on the knowledge of oral hygiene and the current oral
      care practices for patients with dysphagia. Fifty-three registered nurses (RNs)
      completed the questionnaires. The results of the questionnaire indicated that
      although RNs gave more oral care daily to their patients with dysphagia than to
      their patients without dysphagia, they had limited knowledge of drugs that affect
      oral care and of medical conditions associated with poor oral hygiene. Of
      particular concern was the limited knowledge of the link between dysphagia, oral
      hygiene and pneumonia and that some of the current oral care practices may be
      putting patients who have dysphagia at increased risk of developing pneumonia.
      These results are discussed in light of previous research on the topic and
      recommendations are made with regards to oral care training.

PMID- 22413405
TI  - Is training in solution-focused working useful to community matrons?
AB  - This article evaluates the usefulness of a small initiative to train community
      matrons (CMs) in solution-focused (SF) approaches, from the perspective of the
      CMs. A SF approach is a psychologically sophisticated, yet relatively easy-to-use
      psychological model for enhancing care and wellbeing which can help to empower
      patients and promote self-care. Data from questionnaires completed by CMs
      immediately post training and from qualitative interviews conducted 12 months
      later suggest that training in SF approaches is considered useful, useable and
      relevant by the nurses themselves. More specifically, CMs reported that SF
      approaches allowed them to work alongside patients to investigate and amplify
      patients' own expertise in 'living well' despite their difficulties, contributing
      to improved patient self-management, less reliance on the CM, and greater job
      satisfaction for the CM. SF approaches seem to resonate with the current NHS
      drive for greater efficiency and better patient-centred care.

PMID- 22413407
TI  - Legal issues surrounding consent and capacity: the key to autonomy.
AB  - With campaigns from the RCN, Nursing Times and Patients' Association promoting
      dignity and choice in healthcare district nurses need to be aware of the legal
      principle that lie at the heart of autonomy, consent. In the first of a series of
      articles on the principles of patient consent Richard Griffith and Cassam Tengnah
      outline the elements of a valid consent and how important obtaining consent is to
      the propriety of a district nurse's practice.

PMID- 22413408
TI  - Older people deserve better.

PMID- 22413409
TI  - The silo...

PMID- 22413410
TI  - Doctors, CO-OPs and the ACA.

PMID- 22413411
TI  - Which adult patients with hypertension should be screened for primary
      hyperaldosteronism?

PMID- 22413412
TI  - Ocular injuries from shake and bake methamphetamine labs.
AB  - PURPOSE: To review ocular injuries resulting from "shake and bake"
      methamphetamine labs. METHOD: Retrospective case series of 4 patients with ocular
      injuries sustained from "shake and bake" lab explosions. RESULTS: Four men ages
      20-39 underwent complete ophthalmologic examination after an injury from a "shake
      and bake" methamphetamine lab explosion.The mechanism of injury was initially
      misrepresented in each case; the physical findings were suggestive of thermal and
      alkali injury. Visual acuity ranged widely from 20/20 to light perception only.
      Treatment in the acute setting included irrigation, pH monitoring, and
      intraocular pressure lowering. CONCLUSION: Methamphetamine production by means of
      the"shake and bake" method can result in combined thermal and alkali ocular
      injury. Patients who sustain this type of injury may not accurately report the
      mechanism of exposure. Increased awareness of this type of ocular injury may
      increase the rapidity of diagnosis, avoid early misdiagnosis, and ultimately
      improve outcomes.

PMID- 22413413
TI  - A cooperative extension service for primary care in Oklahoma.
AB  - Lessons learned and practiced in agriculture for 100 years are now informing the
      development of a primary care extension program that has the potential to provide
      substantial support for primary care practices throughout Oklahoma and to make it
      easier for all agencies and organizations working to improve our state's health
      to do so more effectively.

PMID- 22413414
TI  - Accountable care organizations: legal concerns.
AB  - The Accountable Care Organizations (ACOs) shared savings program has serious
      concerns about anti-trust and anti-fraud laws. Additionally, ACOs present several
      other legal concerns relating to the duties and responsibilities of the physician
      hospital partnership. The federal regulations hold physicians who participate in
      the ACO shared savings program to the highest standards of care without offering
      them protection from liability. The structure and procedures required of ACOs may
      be detrimental and may significantly impact the liability of its contracting
      physicians. Therefore, it behooves physicians to obtain legal advice regarding
      one's estate planning and legal asset protection or wealth management techniques,
      and to thoroughly review the agreement with one's attorney before signing a
      contract with an ACO.

PMID- 22413415
TI  - Manging diabetes during the holidays.

PMID- 22413416
TI  - Flu vaccines have good safety records.

PMID- 22413417
TI  - Quality improvement through care management and practice facilitation.

PMID- 22413418
TI  - OSMA launches physician trusted HIE for meaningful use!

PMID- 22413419
TI  - Fair exchange.

PMID- 22413420
TI  - [Polish recommendations for the enteral nutrition of adult ITU patients].

PMID- 22413421
TI  - [On certain topical problems of contemporary industrial medicine].
AB  - The article tackles certain problems concerning occupational medicine
      organization work and methodology of its conceptual apparatus used to
      characterize individual and populational health of workers, covers suggestions on
      solving these problems.

PMID- 22413422
TI  - [Legal and methodical aspects of occupational risk management].
AB  - Legal and methodical aspects of occupational risk management (ORM) are considered
      with account of new official documents. Introduction of risk and risk management
      notions into Labor Code reflects the change of forms of occupational health and
      safety. The role of hygienist and occupational medicine professionals in
      workplace conditions certification (WCC) and periodical medical examinations
      (PME) is strengthened. The ORM could be improved by introducing the block of
      prognosis and causation based on IT-technologies that could match systems of WCC
      and PME thus improving the effectiveness of prophylactics.

PMID- 22413423
TI  - [Comparative analysis of occupational disease risk in miners of two coal regions
      with different ways of coal extraction].
AB  - Based on a model created by authors, the authors defined risks and terms of main
      occupational diseases development in miners of coal-extracting regions.

PMID- 22413424
TI  - [On parity in development of obstructive and restrictive changes in miners].
AB  - Spirometric studies in 397 miners having pneumoconiosis and chronic dust
      bronchitis demonstrated 80% occurrence of respiratory failure with equally marked
      obstructive and restrictive disorders. Therefore, bronchopulmonary diseases in
      miners do not match the criteria of chronic obstrictive lung disease.

PMID- 22413425
TI  - [Lung ventilation parameters in various pneumoconiosis forms during follow-up in
      miners of Kouzbass].
AB  - Studies of spirometric parameters in 120 miners who live in Kemerovo region and
      suffer from diagnosed pneumoconiosis demonstrated disordered pulmonary
      ventilation in 53.3% of the examinees. The highest velocity parameters in
      spirometry are seen in nodular form, the lowest ones--in mixed form of
      pneumoconiosis. During 2 years of follow-up forced expiratory volume over the
      first second decreased. Velocity and volume spirometric parameters in
      pneumoconiosis among coal miners of Kemerovo region under 2 years of follow-up
      demonstrate invert correlation with initial age of the patients when
      pneumoconiosis was diagnosed.

PMID- 22413426
TI  - [Remodelling of right heart chambers in patients with occupational respiratory
      diseases in post-contact period].
AB  - Clinical manifestations of occupational respiratory diseases and functional
      cardiorespiratory state in workers were studied in thorough examination of 329
      workers including main occupations of refractory metals alloys production, who
      are exposed to polymetallic highly dispersed aerosols in concentrations exceeding
      the MACs. The data obtained prove changes in intracardial hemodynamics, lower
      myocardial contractility and lung hypertension even at early stages of the
      process, progressing in the advanced disease and in post-contact period. Heart
      remodelling underlies frequent cardiac arrhythmias in occupational respiratory
      diseases. With that, intensity of the changes reliably increases with higher
      degree of bronchial obstruction in the patients and could serve as a marker of
      respiratory failure severity.

PMID- 22413427
TI  - [Life quality of workers engaged into coal-extracting enterprises of Kouzbass].
AB  - Periodic medical examinations on coal-extracting enterprises of Kemerovo region
      included use of questionnaire SF-36. Life quality parameters in coal industry
      workers of Kemerovo region decrease from age 20 to 64 years through all the
      questionnaire scales. Life quality parameters in scales of pain, physical
      functioning and general health demonstrated invert correlation with age and
      length of service in hazardous conditions of coal-extracting industry.

PMID- 22413428
TI  - [Chronic occupational bronchitis: problems and prospects (review of literature)].
AB  - The authors analysed history of "occupational bronchitis" term establishment,
      presented various points of view on defining occupational bronchial obstruction
      diseases, their classification and connections with other diseases. Evaluating
      pathogenetic features of occupational bronchitis, the authors emphasized studies
      of disordered "proteolysis-antiproteolysis" system role, xenobiotics
      biotransformation and free-radical processes. The authors pointed promising role
      of molecular genetic studies for better and more individual system of medical
      care for workers.

PMID- 22413429
TI  - [Osteoporosis and osteosclerosis as parity components of occupational fluorosis].
AB  - Assessment of bone tissue density in aluminium plant workers revealed obligatory
      osteoporosis in them. When primary endocrine disorders ruled out, conclusion can
      be made of osteoporosis along with osteosclerosis as parity components in
      occupational fluorosis, so contemporary methods of osteologic studies are
      necessary for assessment of bone tissue.

PMID- 22413430
TI  - [Dysfunction of cognitive and memory spheres during vibration disease in miners
      of Kouzbass].
AB  - Cognitive and memory dysfunction in vibration disease results from biologic
      effects of industrial vibration in central nervous system and whole human body.
      Early diagnosis of cognitive and memory spheres, and opportune rehabilitation
      measures helps to avoid transition to dementia.

PMID- 22413431
TI  - [Anesthetic agents--Dr. Jekyll or Mr. Hyde?].

PMID- 22413432
TI  - [Alteration of cerebral blood flow by modified electroconvulsive therapy in major
      depression].
AB  - BACKGROUND: Modified electroconvulsive therapy (mECT) aims to improve major
      depression, giving an electronic stimulation to a patient in order to make tonic
      clonic convulsion. Elevation of regional cerebral oxygen saturation (rSO2) was
      reported just after stimulation. Increase of oxygen consumption in brain is
      compensated by increase of cerebral blood flow. Oxygenation and blood flow over
      the entire brain are evaluated by measuring rSO2 at forehead. We followed
      alteration of rSO2 at each mECT. METHODS: rSO2 was measured by INVOS 5100
      (Edwards Lifesciences). Patients had Somasensor placed at the right and left
      forehead, rSO2 was measured from before and after mECT. After general anesthesia
      induction, patients were stimulated by Tymatron SYSTEM IV (Somatics, America).
      Intensity of stimulation was decided by a single psychiatrist. We showed rSO2
      values as follows: before stimulation (before), minimum value after stimulation
      (mini) and maximum value after stimulation (max). Hamilton depression scale (HAM
      D) was used for severity of depression. RESULTS: All patients showed improved HAM
      D. The values of (max-before)/before of rSO2 increased at the end of the therapy.
      CONCLUSIONS: We suggested that the response of cerebral vasculatures for
      electroconvulsive stimulation was improved as depression was improved.

PMID- 22413433
TI  - [Development and evaluation of a patient-reported outcome measure of pain-related
      sleep disturbances for pain clinic patients].
AB  - BACKGROUND: The purpose of this study was to develop a new tool, the Pain Sleep
      questionnaire, consisting of 20 items (PS-20) for measuring pain-related sleep
      disturbances in pain clinic patients, and to examine its reliability and
      validity. METHODS: The internal consistency, criterion validity compared with the
      Medical Outcomes Study 36-item Short-Form Health Survey (SF-36v2), and construct
      validity of the PS-20 were tested. RESULTS: A total of 125 patients participated
      in this study. Cronbach's alpha coefficient was 0.969, indicating good internal
      consistency. The PS-20 score correlated moderately with the physical component
      summary of SF-36v2 and correlated weakly with the mental component summary of SF
      36v2. From the graphical model using the Akaike information criterion and the
      Categorical principal component analysis, the items were divided into four
      domains: physical pain, trouble falling asleep, awakened by pain, and general
      health problems. CONCLUSIONS: The PS-20 was shown to be a valid and reliable
      questionnaire scale for measuring pain-related sleep disturbances among pain
      clinic patients.

PMID- 22413434
TI  - [Difficulty in left-sided double-lumen tube placement in patients undergoing
      surgical graft replacement of the descending aorta is predicted from
      tracheobronchial compression].
AB  - BACKGROUND: In surgical graft replacement of the descending aorta graft, one-lung
      ventilation (OLV) is required to provide adequate surgical view and to allow
      removal of blood from the left lung. It is best to use a double-lumen tube (DLT)
      to assure OLV but it is sometimes difficult to place the left-sided DLT due to
      thoracic aneurysm or the dissection lumen. We retrospectively investigated
      tracheobronchial anatomy by chest X-ray and chest computed tomography (CT) in 29
      cases of descending aorta replacement to determine how best to manage difficult
      placement of the left-sided DLT. METHODS: From our database of 29 patients who
      had undergone descending aorta replacement between February 1, 2005, and December
      31, 2009, we investigated the association between difficulty in placing the left
      sided DLT and tracheobronchial anatomy by chest X-ray and CT. RESULTS: We could
      not place a left-sided DLT in 3 of 29 cases. Two of these cases were planned
      surgery for aortic aneurysm and the other was an emergency operation for acute
      aortic dissection. We could manage the two cases safely using a right-sided DLT.
      We compared chest X-ray and chest CT images of these 3 cases with the other 26
      cases and found that compression of the tracheobronchial tree was prevalent in
      the cases of difficult placement of the left-sided DLT. CONCLUSIONS: We
      experienced difficulty in placement of the left-sided DLT in 3 of 29 cases of
      descending aorta replacement. We can predict difficulty of left-sided DLT
      placement by the presence of compression of the tracheobronchial tree on chest
      CT.

PMID- 22413435
TI  - [Comparison of the Parker flex-tip tube with the standard tube for Airtraq
      intubation].
AB  - BACKGROUND: During tracheal intubation with the Airtraq laryngoscope (AL), the
      tracheal tube tip sometimes impinges on the glottis or other laryngeal
      structures. We tested a hypothesis that Parker flex-tip tube (PT) makes AL
      assisted tracheal intubation easier and faster than a conventional tube
      (Mallinckrod Hi-Lo tube : HT). METHODS: Study 1. Fifty patients were assigned to
      group PT (n = 25) or group HT (n = 25). After induction of general anesthesia,
      intubation was performed with AL. We recorded tube passage time, the number of
      tube impingements, circulatory changes and incidences of postoperative
      complications. Study 2. Twenty patients were divided into two groups and
      intubated either by HT or PT. We assessed the tip direction and contact points of
      each tube. RESULTS: Study 1. The use of PT significantly reduced the number of
      tube impingements compared to HT. Tube passage time in group PT was shorter than
      that in group HT, but the difference was not statistically significant. Study 2.
      The tube tip contact with the vocal cords was more frequent with HT. CONCLUSIONS:
      PT significantly reduced the number of impingements. The shape of tube tip and
      the smaller angle of PT when fitted in AL contributed to the relative ease of
      tube passage.

PMID- 22413436
TI  - [Retrospective evaluation of pregabalin for cancer-related neuropathic pain].
AB  - BACKGROUND: Evidence to support the use of pregabalin in combination with opioid
      analgesics for the treatment of cancer-related neuropathic pain is limited.
      METHODS: We carried out a retrospective investigation on patients hospitalized in
      our department with cancer-related neuropathic pain and under pregabalin
      treatment. Patients were divided into two groups: A group (= < 300 mg pregabalin
      daily) and B group (> 300 mg pregabalin daily). The two groups were compared in
      terms of a suite of factors (e. g., age starting and maimtenance dose of
      pregabaline, adverse effect). RESULTS: Patient's age was significantly lower in
      the B group (> 300 mg pregabalin daily). Of the total number of patients involved
      in the study, 67% experienced mild and moderate somnolence. CONCLUSIONS: In this
      retrospective investigation, we conclude that the younger cancer patients may
      need lager doses of pregabalin to relieve cancer-related neuropathic pain. In
      addition, the mild and moderate somnolence occurs frequently when pregabalin is
      administered with opioid analgesics for the treatment of cancer-related
      neuropathic pain.

PMID- 22413437
TI  - [Effect of postoperative analgesia by repeated transversus abdominis plane blocks
      via a placed catheter in patients undergoing ovarian cystectomy].
AB  - BACKGROUND: We evaluated the effect of repeated transversus abdominis plane (TAP)
      blocks on postoperative analgesia over the first 48 postoperative hours in the
      patients undergoing lower abdominal gynecological surgery. METHODS: Four patients
      undergoing ovarian cystectomy via a transverse lower abdominal wall incision were
      selected. All patients received general anesthesia. After the operation,
      bilateral TAP blocks were performed by ultrasound-guided access using 0.375%
      ropivacaine 15 ml, and a catheter was placed on the plane. Repeated TAP blocks
      were performed every 12 hours using 0.375% ropivacaine 15 ml until the second
      postoperative day. Each patient was assessed for the analgesic effect and
      complications at 3, 6, 12, 24, 36, and 48 hours postoperatively. RESULTS: The
      postoperative visual analogue scale pain scores at rest and on movement were
      approximately under 20. The median frequency of additional nonsteroidal anti
      inflammatory drugs until the second postoperative day was 0.5. We did not observe
      any complications such as nausea, vomiting and shivering in the postoperative
      period. CONCLUSIONS: These findings suggest that bilateral repeated TAP blocks
      via a placed catheter provide good analgesia without any complications in
      patients undergoing ovarian cystectomy.

PMID- 22413438
TI  - [Effect of landiolol hydrochloride for intraoperative tachycardia--multicenter
      questionnaire study].
AB  - BACKGROUND: The purpose of this study was to evaluate effects of landiolol
      hydrochloride, which is an ultra-short-acting beta-1 selective blocker, for
      intraoperative tachycardia and to establish practical methods of administration
      of the drug. METHODS: We retrospectively examined by multicenter questionnaires
      the effects and practical methods of administration of landiolol for 100 patients
      who showed tachycardia needing treatment during anesthesia. The techniques for
      anesthesia and administration of landiolol were entrusted to each
      anesthesiologist. RESULTS: One case was excluded because the dose of landiolol
      hydrochloride was uncertain. Fifty-nine patients received an intravenous bolus
      injection of landiolol, and continuous injection was performed in 34 patients.
      Six patients had both bolus and continuous injections. In the 99 patients, heart
      rate was significantly reduced to desired levels. The time required to reduce
      heart rate by more than 10% after injection was shorter in the bolus group than
      in the continuous group. Bolus injection, however, did not reduce blood pressure.
      Although low-dose continuous administration significantly reduced blood pressure,
      treatment for increasing blood pressure was not needed in any of the patients.
      CONCLUSIONS: Information obtained by the questionnaire suggests that bolus
      injection and/or low-dose continuous administration of landiolol, which are not
      described in the drug information documents, are effective and safe for treatment
      of tachycardia during anesthesia.

PMID- 22413439
TI  - [Detectors of fluid absorption during transurethral resection of prostate using
      saline as irrigant solution].
AB  - BACKGROUND: Although transurethral resection of prostate (TURP) using saline as
      irrigant solution (TURis) is reported to reduce intraoperative hyponatremia,
      careful management during operation is needed to avoid complications caused by
      possible massive absorption of irrigant solution. METHODS: To find out the
      detectors of fluid absorption during TURP using TURis system, intraoperative data
      of hemodynamics and serum electrolytes in 11 patients who had TURP using TURis
      system were retrospectively collected and statistically analyzed. RESULTS: During
      TURP using TURis system, serum chloride (s-Cl) significantly increased (before/60
      min after beginning of operation: 99.4 +/- 2.8/104.2 +/- 5.1 mEq x l(-1), mean +/
      SD). Intraoperative changes in s-Cl had strong correlations with changes in base
      excess, serum potassium, hematocrit and central venous pressure. CONCLUSIONS: Our
      results suggested intravenous absorption of saline solution during operation.
      Serum chloride concentration can be a useful detector of irrigant solution
      absorption during TURP using TURis system.

PMID- 22413440
TI  - [Predictive analysis for myasthenic crisis after transsternal thymectomy in
      patients with myasthenia gravis].
AB  - BACKGROUND: The risk factors for postoperative myasthenic crisis (MC) in patients
      with myasthenia gravis (MG) receiving preoperative corticosteroids were unknown.
      METHODS: Sixty-three consecutive patients who had undergone a transsternal
      thymectomy for MG were retrospectively analyzed. Of these, 59 patients (93.7%)
      received preoperative corticosteroids (prednisolone 1-2 mg x kg(-1)) every-other
      day. In this study, our definition of postoperative-MC was the need for prolonged
      postoperative mechanical ventilation for more than 48 hours. Six patients (9.5%)
      met this criterion. The patient background, and preoperative as well as
      intraoperative management were evaluated to identify risk factors for
      postoperative-MC. RESULTS: Student's t-test revealed that the lengths of the
      operation and anesthesia were significantly longer in the postoperative-MC group
      compared with the control group (P < 0.05). Fisher's exact test revealed that the
      existence of preoperative bulbar symptoms and incomplete resection of the thymus
      gland were also more common in the postoperative-MC group (P < 0.05). A logistic
      regression analysis revealed that the existence of preoperative bulbar symptoms
      was the only significant risk factor for postoperative-MC. CONCLUSIONS: Based on
      this study, we concluded that the existence of preoperative bulbar symptoms seems
      to be a predictor for the development of postoperative-MC in patients with MG
      undergoing a transsternal thymectomy.

PMID- 22413441
TI  - [Prevention of spinal hypotension associated with cesarean section by aortocaval
      compression--left 15 degree table tilt vs. uterine displacement by hand].
AB  - Women undergoing elective cesarean delivery were randomly assigned to receive a
      spinal anesthesia in either the semi-lateral (group SL) position or the supine
      position with uterine displacement (group UD). After spinal injection, group SL
      patients were turned to a 15 degrees left lateral supine position, and group UD
      patients had uterine displacement by hand. Ephedrine 4 mg i.v. was administered
      in case of nausea/vomiting and/or hypotension, defined as a systolic blood
      pressure below 100 mmHg. Arm systolic arterial pressure and leg systolic arterial
      pressure were similar in both groups, but the lowest leg systolic arterial
      pressure until delivery was significantly lower in the UD group (P < 0.05). Mean
      ephedrine requirement was significantly less in the SL group (P < 0.05). Apgar
      scores did not differ, but umbilical artery pH values were significantly higher
      in patients of the group SL (P < 0.01).

PMID- 22413442
TI  - [Anesthesia for laser surgery of a tracheal tumor involving the carina:
      preservation of spontaneous breathing using remifentanil].
AB  - We describe anesthetic management of a patient with airway stenosis due to a
      tracheal tumor involving the carina. A 68-year-old man developed dyspnea and was
      scheduled for YAG laser surgery under general anesthesia. Awake fiberoptic
      intubation was selected for anesthesia induction, and percutaneous
      cardiopulmonary support (PCPS) was ready to be established prior to induction of
      anesthesia. Anesthesia was maintained with remifentanil (0.05 microg x kg(-1) x
      min(-1)) and propofol (2 mg x kg(-1) x hr(-1)), and spontaneous breathing was
      preserved throughout the surgical procedure. The operation was completed
      successfully without any adverse events, and PCPS was not used. In this patient,
      preservation of spontaneous breathing using remifentanil was found to be useful
      for airway management.

PMID- 22413443
TI  - [Case of difficult ventilation due to trachea stricture during general anesthesia
      in a morbidly obese patient].
AB  - Obesity has various coexisting illnesses, and the risk of the anesthesia
      management in an obese patient is high. We report a case of difficult ventilation
      by trachea stricture during general anesthesia in a morbidly obese patient.

PMID- 22413444
TI  - [Case of laryngopharyngeal edema after a spinal tumor resection in prone position
      with extensive neck flexion].
AB  - A 63-year-old woman developed laryngopharyngeal edema after a cervical spinal
      tumor resection in prone position. The tracheal tube was removed after 11 hours
      of general anesthesia and nasal airway was inserted because stridor was audible.
      Blisters were found on the skin of the anterior neck of the patient. Examinations
      at 3 h after the extubation suggested upper airway stenosis including stridor,
      increased work of breathing, oxygenation impairment, and hypercapnia. The trachea
      of the patient was intubated and the examination of the upper airway by inserting
      a fiberoptic bronchoscope through the patient's mouth revealed laryngopharyngeal
      edema. It was considered that the disturbance of venous and/or lymphatic flow of
      anterior neck due to extensive neck anteflexion during the surgery in prone
      position had induced the laryngopharyngeal edema; however, we could not verify
      the cause of the edema. The edema persisted for weeks. We conclude that we should
      avoid extensive neck anteflexion during surgery in prone position and it is
      recommended to observe the upper airway for a few hours after extubation because
      there could be airway obstruction due to delayed and/ or progressive
      laryngopharyngeal edema.

PMID- 22413445
TI  - [Anesthetic management of a patient with stiff-person syndrome undergoing
      thymectomy].
AB  - Stiff-person syndrome is an uncommon disease characterized by muscular rigidity
      and painful spasms in the axial and limb muscles. We report a 58-year-old woman
      with stiff-person syndrome undergoing thymectomy under general anesthesia. Before
      surgery, her medications were 25 mg of diazepam, 2 mg of clonazepam, and 15 mg of
      gabapentin per day. After epidural catheterization for the postoperative
      analgesia, general anesthesia was induced and maintained with continuous
      remifentanil infusion and propofol with target controlled infusion. With train-of
      four ratio (TOFR) monitoring by stimulating the ulnar nerve, her trachea was
      intubated after 0.6mg x kg(-1) of rocuronium intravenous administration. Since
      then, additional rocuronium was not given for 4 hours. After surgery, she was
      fully awake and TOFR recovered to 100%, but tidal volume was too low to remove
      the tracheal tube, and mechanical ventilation was continued in ICU. On the next
      day, the tracheal tube was removed, and she was discharged from ICU. Because
      anesthetics may delay the recovery of respiratory function in a patient with
      stiff-person syndrome, careful assessment of respiratory function is needed at
      the emergence from general anesthesia.

PMID- 22413446
TI  - [Hyperlactemia during undiagnosed pheochromocytoma resection under laparoscopy].
AB  - A 51-year-old man was scheduled to undergo adrenal tumor resection. Because his
      general physical findings and labolatory tests were not particular, and his serum
      concentrations of noradrenaline and adrenaline were within normal limit, the
      tumor was diagnosed as nonfunctional adrenal tumor. Anesthesia was induced with
      propofol, fentanyl and maintained with oxygen, air, propofol and remifentanil.
      When the surgeons started to work around the tumor, his blood pressure and heart
      rate increased suddenly. We decided to deal with the tumor as pheochromocytoma
      and started administering landiolol and prostaglandin E1. After the
      administration of the drugs, hemodynamic changes became stabilized; however, the
      increasing serum concentration of lactate continued until ligation of the adrenal
      vein. There were no clinical manifestations of circulatory failure and his liver
      function was within normal limits from his blood test. After the operation, we
      found his plasma concentration of adrenaline extremely high during the operation.
      Adrenaline increases blood lactate concentration due to metabolic effects.
      Hyperlactemia should be considered as one of the typical symptoms of
      pheochromocytoma.

PMID- 22413447
TI  - [Anesthetic management for a case of an isolated congenital unilateral absence of
      the right pulmonary artery].
AB  - Isolated unilateral absence of the right pulmonary artery without any
      intracardiac anomaly (APA) is a rare congenital cardiovascular disorder. We
      report a case of a 47-day-old female infant with right APA who underwent
      pulmonary angiogram under general anesthesia. Induction and maintenance of
      anesthesia consisted of total intravenous anesthesia with propofol, remifentanil
      and vecuronium. Hemodynamic status and oxygenation were stable throughout the
      examination. Mean pulmonary artery pressure was 22 mmHg. During
      bronchofiberscopic examination through an endotracheal tube, SpO2 rapidly
      decreased from 98% to 50% in 10 s despite sufficient preoxygenation with 100%
      oxygen. Our case suggests that a care must be taken for desaturation during
      procedures without ventilation in PAP patients.

PMID- 22413448
TI  - [Anesthetic management of a patient with pulmonary hypertension due to a large
      anterior mediastinal tumor anticipated by preoperative computed tomography].
AB  - A 74-year-old man underwent an operation for an extremely large mediastinal
      tumor. Despite the lack of respiratory difficulty or distention of the jugular
      veins, preoperative computed tomography showed suppression of the left atrium by
      the huge tumor. We suspected pulmonary hypertension and monitored continuously
      with a pulmonary catheter. The Pp/Ps ratio decreased gradually from 0.8 to 0.7 by
      continuous administration of alprostadil or olprinone. After tumor resection, the
      Pp/Ps ratio was reduced and maintained at 0.2 even after alprostadil and
      olprinone administration was discontinued. The tumor was considered to have
      caused the severe pulmonary hypertension, as anticipated from the preoperative
      CT.

PMID- 22413449
TI  - [Case in which massive hydroxyethylated starch (HES) infusion was useful for
      massive hemorrhage in spite of progressive hemodilution].
AB  - A 72-year-old man with no internal complication underwent total prostatectomy.
      During operation, massive hemorrhage occurred. Because of delay in transfusion,
      hemodilution progressed until minimum hemoglobin concentration of 1.6 g x dl(-1):
      minimum hematocrit of 4.8%. In spite of this extreme hemodilution, we could
      stabilize his hemodynamics and he recovered without any apparent damage in major
      organs. For management of hemodynamics a massive dose of hydroxyethylated starch
      (HES) was infused to maintain the intravascular volume. For massive hemorrhage,
      HES infusion may be useful to keep hemodynamics in spite of progressive
      hemodilution.

PMID- 22413451
TI  - [Case of pneumonitis caused by Yokukansan].
AB  - A 74-year-old man was admitted to our hospital complaining of severe neck pain
      and general fatigue. He had been undergoing treatment for post-operative neck
      pain at the out-patient clinic of our hospital, but was now complaining of pain
      more intense than usual. Chest X-rays revealed diffuse ground glass shadows in
      bilateral lung fields, and computed tomography revealed diffuse intestinal
      shadows. A drug lymphocyte stimulation test (DLST) was also performed at that
      time. Steroid pulse therapy improved the clinical symptoms, hypoxemia and chest X
      ray findings. DLST performed again with Yokukansan and Hachimijiogan 133 days
      after the initial diagnosis of pneumonitis showed Yokukansan was positive. This
      result showed Yukukansan may be a causative drug for allergic drug-induced
      pneumonitis. Any drugs including kanpo may be possible to induce allergic
      pneumonitis.

PMID- 22413450
TI  - [Sudden increases and decreases in bispectral index values more than 30 within 1
      minute during general anesthesia].
AB  - We described, in a 40-year-old man, sudden and unexpected increases in bispectral
      index values during the general anesthesia with total intravenous anesthesia
      using propofol in a dental surgery. The patient was administered continuous
      infusion of propofol and remifentanil, and intermittent supplementation of
      fentanyl. Immediately after the beginning of surgery, the bispectral index value
      increased abruptly to 90; whereas, heart rate and non-invasive blood pressure
      were unchanged and no physiological finding was observed. Approximately 25 min
      later, the value decreased to below 40 without any modification of anesthesia.
      The extent of unanticipated increase might be compatible with the duration of
      surgical procedure using dental air turbine. Therefore, the noise from surgical
      device might induce unpredictable change in bispectral index values.

PMID- 22413452
TI  - [Effect of landiolol on bispectral index scores in patients undergoing lower
      abdominal surgery].
AB  - BACKGROUND: The aim of this study was to examine the effects of landiolol on
      bispectral index scores (BIS) during surgery. METHODS: Twenty patients undergoing
      total hysterectomy were allocated into two groups; 1) 10 patients not receiving
      landiolol (C group), 2) 10 patients receiving landiolol 125 microg x kg(-1) x
      min(-1) for one minute followed by 40 microg x kg(-1) x min(-1) (L group). They
      were anesthetized with sevoflurane (end-tidal concentration of 1.0%) combined
      with a continuous infusion of remifentanil at 0.25 microg x kg(-1) x min(-1).
      Mean arterial pressure (MAP), heart rate (HR) and BIS were recorded 4 times
      (immediately before the skin incision, 5 minutes after the skin incision, at the
      moment of uterine extraction and during retroperitoneal closure). RESULTS: No
      significant differences were found in MAP and BIS between the groups at any time
      points, while HR in the L groups was lower than that in the C group throughout
      the study period. CONCLUSIONS: This study suggests that landiolol has no effects
      on BIS in patients undergoing lower abdominal surgery during sevoflurane
      remifentanil anesthesia.

PMID- 22413453
TI  - [Comparison of ultrasound-guided and blindly placed radial artery
      catheterization].
AB  - BACKGROUND: The purpose of this study was to evaluate whether ultrasound (US)
      guided radial artery catheterization decreases the number of failed attempts.
      METHODS: A total of 36 patients requiring an arterial catheter were enrolled.
      Patients were divided into 3 groups: 1) a blind palpation technique group, 2) an
      US-guided short-axis group, and 3) an US-guided long-axis group. The vascular
      access was performed by one anesthesiologist. The number of attempts at catheter
      placement was compared within the groups. RESULTS: There were no significant
      differences among the groups in number of attemps (P = 0.268); however, it seems
      that the deviation of attempts was small in the US groups. CONCLUSIONS: Because
      the artery and catheter are actually visualized by US, it seems, that US-guided
      radial artery catheterization is a safe and educational technique.

PMID- 22413454
TI  - [Pancreatic tumor: progress in diagnosis and treatment. Editorial: trend of
      clinical management of pancreatic tumors].

PMID- 22413455
TI  - [Pancreatic tumor: progress in diagnosis and treatment topics: I. Pancreatic
      carcinoma; 1. Epidemiology, risk factor, symptom].

PMID- 22413456
TI  - [Pancreatic tumor: progress in diagnosis and treatment. Topics: I. Pancreatic
      carcinoma: 2. Pathogenesis and pathobiology in pancreatic cancer.--The molecular
      mechanisms of carcinogenesis, and invasion and metastasis in pancreatic cancer].

PMID- 22413457
TI  - [Pancreatic tumor: progress in diagnosis and treatment. Topics: I. Pancreatic
      carcinoma; 3. Differential diagnosis of pancreatic cancer].

PMID- 22413458
TI  - [Pancreatic tumor: progress in diagnosis and treatment. Topics: I. Pancreatic
      carcinoma; 4. Progress of non-surgical treatment for pancreatic cancer].

PMID- 22413459
TI  - [Pancreatic tumor: progress in diagnosis and treatment. Topics: I. Pancreatic
      carcinoma; 5. Improvements in surgical treatment].

PMID- 22413460
TI  - [Pancreatic tumor: progress in diagnosis and treatment. Topics: I. Pancreatic
      carcinoma; 6. Evidence based clinical practice guidelines for pancreatic cancer
      2009].

PMID- 22413461
TI  - [Pancreatic tumor:progress in diagnosis and treatment. Topics: II. Intraductal
      papillary mucinous neoplasm of the pancreas (IPMN) /mucinous cystic neoplasm
      (MCN); 1. Symptoms and surveillance of IPMN and MCN].

PMID- 22413462
TI  - [Pancreatic tumor: progress in diagnosis and treatment. Topics: II. Intraductal
      papillary mucinous neoplasm of the pancreas (IPMN)/mucinous cystic neoplasm
      (MCN); 2. Pathology and pathobiology].

PMID- 22413463
TI  - [Pancreatic tumor:progress in diagnosis and treatment. Topics: II. Intraductal
      papillary mucinous neoplasm of the pancreas (IPMN)/mucinous cystic neoplasm
      (MCN): 3. Differential diagnosis of pancreatic cystic lesions with special
      emphasis on IPMN and MCN].

PMID- 22413464
TI  - [Pancreatic tumor: progress in diagnosis and treatment. Topics: II. Intraductal
      papillary mucinous neoplasm of the pancreas (IPMN) mucinous cystic neoplasm
      (MCN); 4. Current therapies for IPMN and MCN].

PMID- 22413465
TI  - [Pancreatic tumor:progress in diagnosis and treatment. Topics: II. Intraductal
      papillary mucinous neoplasm of the pancreas (IPMN)/mucinous cystic neoplasm(MCN);
      5. Management and diagnosis and therapeutic strategies for intraductal papillary
      mucinous neoplasm of the pancrea : IPMN].

PMID- 22413466
TI  - [Pancreatic tumor: progress in diagnosis and treatment. Topics: II. Intraductal
      papillary mucinous neoplasm of the pancreas (IPMN)/mucinous cystic neoplasm
      (MCN): 6. Other cystic neoplasms of the pancreas].

PMID- 22413467
TI  - [Pancreatic tumor: progress in diagnosis and treatment. Topics: III. Pancreatic
      endocrine tumor; 1. Epidemiology, symptoms and diagnosis].

PMID- 22413469
TI  - [Pancreatic tumor: progress in diagnosis and treatment. Topics: III. Pancreatic
      endocrine tumor; 3. Multiple endocrine neoplasia].

PMID- 22413470
TI  - [Discussion meeting on is it possible to detect pancreatic cancer in early
      stage?].

PMID- 22413468
TI  - [Pancreatic tumor: progress in diagnosis and treatment. Topics: III. Pancreatic
      endocrine tumor; 2. Current status of the treatment of pancreatic neuroendocrine
      tumors].

PMID- 22413471
TI  - [Case report; Chronic neutropenia with variegated infectious symptoms].

PMID- 22413472
TI  - [Case report; Three cases of chronic renal failure with hypokalemia; possible
      involvement with villous adenoma of the colon].

PMID- 22413473
TI  - [Case report; Two cases of neurolymphomatosis as a manifestation of relapsed non
      Hodgkin lymphoma].

PMID- 22413474
TI  - [Case report; Two cases of crowned dens syndrome].

PMID- 22413475
TI  - [Case report; November fever--the clinical features of scrub typhus by
      Leptotrombidium scutellare in south-central Fukushima Prefecture].

PMID- 22413476
TI  - [Case report: Reversible posterior leukoencephalopathy associated with the
      treatment of multiple myeloma: a case report].

PMID- 22413477
TI  - [The cutting-edge of medicine; the hypertensive disorders of pregnancy and
      kidney; classification, diagnosis and management].

PMID- 22413478
TI  - [The cutting-edge of medicine; recent topics on cancer prevention and screening:
      risk-benefit balance].

PMID- 22413479
TI  - [Series: Knowledge of emergency required for internist; hypertensive crisis].

PMID- 22413480
TI  - [Series: Clinical study from Japan and its reflections; KYOTO HEART study].

PMID- 22413481
TI  - [Series: Diagnosis at a glance].

PMID- 22413482
TI  - [Series: For attending physicians; professionalism: teaching medical
      professionalism and the impact of the hidden curriculum].

PMID- 22413483
TI  - [Endoscopic sinus surgery complications a prospective multicenter study].
AB  - OBJECTIVE: Our objective was to determine the rate of complications in endoscopic
      sinus surgery (ESS) and associated risk factors. METHODS: We prospectively
      studied 1,382 subjects undergoing ESS for rhinosinusitis and cystic sinus disease
      at 16 hospitals during 2007 and 2008. Surgeons provided information on peri-and
      postoperative complication occurrence. RESULT: Results of complications were seen
      in 80 subjects (5.8%), the most frequent was perioperative lamina papyracea
      injury. Analysis showed the complication rate to be linked to gender, and
      anesthesia type, but not the grade of surgeon. CONCLUSIONS: While care should be
      taken to avoid them, complications should be identified and treated in a timely
      and accurate manner.

PMID- 22413484
TI  - [Tonsillectomy in recurrent IgA nephropathy after renal transplantation].
AB  - Many reports suggest tonsillectomy efficacy in subjects with early-stage IgA
      nephropathy (IgAN). Post-renal-transplant treatment in recurrent IgAN must,
      however, be assessed carefully. Recent reports show that tonsillectomy to also be
      effective in such recurrent cases. We studied 13 subjects with recurrence
      diagnosed histopathologically in allogenic kidney transplantation involving
      tonsillectomy from March 2008 to March 2010. Tonsillectomy was done on average of
      74 months (15-180 months) after transplantation. Subjects averaged 44.8 years of
      age (29-67 years old). Buried tonsil was most common and 12 of 13 involved pus.
      One subject suffered slight bleeding 1 week after tonsillectomy, manageable
      conservatively. Steroid pulse therapy was added in 1 case after tonsillectomy due
      to histopathological renal biopsy suggesting severe renal injury. In most cases,
      serum creatinine (SCr) and urinary findings improved after tonsillectomy, which
      is thus expected to be effective in subjects with recurrent early-stage IgAN
      following renal transplantation, not only in those with IgAN.

PMID- 22413485
TI  - [Neuroimaging of neuropsychiatric disorders].

PMID- 22413486
TI  - [Epidemiology of psychiatric disorders among medically ill patients].
AB  - This article reviews recent epidemiological findings on the relationship between
      physical and psychiatric conditions. First, physical disorders may be a risk
      factor of mental disorders. The WHO World Mental Health (WMH) Surveys indicated
      that the prevalence of most mental disorders were high among persons with a
      variety of physical disorders. Second, mental disorders may affect the course and
      prognosis of physical disorders. Several studies reported increased mortality
      when depression was comorbid with cancer, stroke, heart disease and diabetes.
      Third, social functioning was more deteriorated among those with comorbid
      physical and mental disorders than those with either of them. The comorbidity
      with mental disorders and its impact on the longevity and social life are
      observed for most physical disorders.

PMID- 22413487
TI  - [How to prescribe psychotropic drugs in primary care].
AB  - What primary care physicians should consider when prescribing psychotropic drugs
      was described. (1) Diagnosis of mental disorders and target symptoms of
      pharmacotherapy should be clarified before prescribing psychotropic drugs. (2)
      Psychological treatments are as important as pharmacotherapy. (3) Psychotropic
      drugs should begin from a small amount and increased gradually. (4) Placebo
      effects are large in the pharmacotherapy of mental disorders. (5) Motor ataxia,
      dizziness, delirium and paradoxical reaction should be noted in prescribing
      benzodiazepines. (6) Headache, diarrhea, nausea, and activation and withdrawal
      syndromes are often seen in the treatment using SSRIs, though their side effects
      are believed to be few.

PMID- 22413488
TI  - [Collaboration with psychiatrists and other mental health professionals].
AB  - A large body of evidence shows that a bidirectional relationship exists between
      mental disorders, such as depression, and medical illnesses, which has a negative
      impact on the prognosis and treatment of either the former or latter condition.
      An adequate collaboration among primary health care professionals, specialist
      physicians, and psychiatrists is required. Various mental health care models,
      including multidisciplinary collaborative care model, as well as guidelines for
      depressive disorders have been developed in the primary care setting. In these
      models, patients have a much better guarantee of accessing integrated care than
      patients referred to a second-line mental health care setting, which is currently
      a common practice in Japan.

PMID- 22413489
TI  - [Drug interactions of psychotropic drugs].
AB  - For the appropriate use of psychotropic drugs, such as hypnotics, antidepressants
      and antipsychotics, knowledge of the pharmacokinetic characteristics and the
      interactions of these drugs are required. The mechanisms of drug interaction can
      be subdivided into pharmacokinetic interactions and pharmacodynamic interactions.
      Among the former, interactions involving inhibition or induction of cytochrome
      P450 (CYP) enzymes are clinically very important. If such interactions cause an
      increase of systemic exposure to psychotropic drugs, adverse effects are likely,
      while a decrease exposure may lead to treatment failure. In this article, we
      review drug interactions of psychotropic drugs from the viewpoints of clinical
      evidence, mechanism, and management.

PMID- 22413490
TI  - [Anxiolytic].
AB  - This chapter outlines the clinician' s guide for prescription of benzodiazepine
      anxiolytics and 5-HT1A receptor agonists. 5-HT1A receptor agonists have entirely
      different pharmacological mechanism of action from benzodiazepines, and the
      pattern of their use is quite different from benzodiazepines. In the global
      trend, there are strict regulations for the prescription of benzodiazepines,
      because of the risk of low-dose dependence. Benzodiazepines are recommended for
      the use only when necessary in the short term. In contrast, benzodiazepines have
      many clinical indications, compared with 5-HT1A receptor agonists. In Japan,
      there is no strict regulation to prescription of benzodiazepines. However, we now
      tend to follow international trends in general.

PMID- 22413491
TI  - [Antidepressants: clinical guidance of treatment for people with depression and
      physical health problems].
AB  - Current management in primary care of depression with comorbid physical illness
      is considered suboptimal. Detection and management of depression is somewhat
      complex. In particular, primary care clinicians need guidance to address the
      social needs of depressed patients. This review for clinical physicians provides
      guidance how to treat those patients with depression in particular at primary
      care settings. The viewpoints of clinical use of newer antidepressants including
      SSRIs and SNRIs are described. Given that depression would affect the outcome of
      physical illness, managing depressed people with comorbid physical illness is
      very important and understanding relevant drug treatment for depression is
      essential for primary care physicians.

PMID- 22413492
TI  - [Hypnotics].
AB  - Several epidemiological studies have shown that more than 20% of the general
      adult population has symptoms of insomnia. Sleep disorders have been reported to
      underlie the development and deterioration of several comorbid diseases such as
      hypertension, cardiovascular diseases, diabetes and depression. It has also been
      documented that prevalence of insomnia is higher in subjects suffering from
      physical diseases. Therefore, most patients with insomnia first consult a general
      practitioner. Various kinds of hypnotics are prescribed mainly by general
      practitioners or non-sleep-medicine expert physicians. Therefore transferring
      clinical knowledge on insomnia from sleep medicine specialists to general
      practitioners is important. In this review article, I described pathophysiology
      and treatment of insomnia, with special reference to the use of hypnotic agents.

PMID- 22413494
TI  - [Antipsychotic drugs].
AB  - Antipsychotic drugs have been widely used in the treatment of organic, including
      symptomatic, mental disorders. The guidelines for the treatment of delirium
      suggest using atypical antipsychotic drugs for the patients with excitement.
      Atypical antipsychotic drugs show higher affinity for 5-HT2A receptor than D2
      receptor. The extrapyramidal side effects of atypical antipsychotic drugs are
      less than of conventional antipsychotic drugs, so they can be used more safely in
      the medication for elderly patients. However, we must pay attention to the risk
      of hyperglycemia, diabetic ketoacidosis and sudden cardiac death. Because of off
      label use, well informed consents about effectiveness and safety are necessary.

PMID- 22413493
TI  - [Mood stabilizers].
AB  - Mood stabilizers available in Japan include lithium, valproate, carbamazepine,
      and lamotrigine. These are prescribed for manic or hypomanic episodes of bipolar
      disorder, organic mania, and drug-induced mania. Careful dose titration is needed
      in consideration for serum drug level and clinical symptoms. Lithium frequently
      develops neurological toxicity because of its narrow therapeutic serum level.
      Valproate has the most favorable adverse effect profile among mood stabilizers,
      but gastrointestinal symptoms and weight gain can appear with a dose dependent
      fashion. Hyperammonemia is occasionally induced early after initiation of
      valproate and tends to be overlooked. Carbamazepine sometimes develops liver
      dysfunction and skin disorders associated with allergic mechanisms. Lamotrigine
      should be slowly titrated to avoid severe skin disorders such as Stevens-Johnson
      syndrome.

PMID- 22413495
TI  - [Endocrine disorders and metabolic disorders].
AB  - Psychiatric symptoms associated with endocrine disorders and metabolic disorders
      have been well recognized. Common endocrine/metabolic disorders that frequently
      cause psychiatric symptoms, thyroid disease, adrenal disorders, parathyroid
      disease, diabetes, electrolyte disturbance are reviewed, especially focusing on
      usage of psychotropic medicine. Psychotropic medication targeting each
      psychiatric symptom would be recommended for patients with moderate to severe
      psychiatric symptoms. However, it should be considered that psychotropic medicine
      might affect background endocrine/metabolic disorders themselves. Risk/benefit of
      the medication should be deliberated for individual cases.

PMID- 22413496
TI  - [Psychopharmacological treatment of patients complicated with cardiovascular
      disease].
AB  - We've had many opportunities of treating psychiatric problems of patients with
      cardiovascular diseases(CVD). Several studies have shown the close relationship
      between psychological factors and CVD. Depression and anxiety increase a
      prevalence of and worsen a prognosis of CVD. Looking at these patients, we must
      consider the following: psychotropics-induced hypotension and QT prolongation
      (antipsychotics and tricyclic antidepressants), cardiovascular drugs induced
      psychiatric symptoms(diuretics), and cardiac and psychiatric drugs interaction,
      especially in cytochrome P450 activity(fluvoxamine and paroxetine). Besides a
      psychopharmacological treatment, psychological approaches based on a therapeutic
      relationship are important in a cardiac rehabilitation setting.

PMID- 22413497
TI  - [Application and indication of psychotropic drugs for respiratory diseases].
AB  - Respiratory symptoms are induced not only by the organic stimulation of air tract
      but also by emotional irritation. Symbolic respiratory reactions and symptoms
      like a cough and dyspnea may develop when human's eomotion is affected by a
      psychosocial stressor. It is important to differentiate so-called psychosomatic
      disorders of respitratory system because it may easily take the chronic course
      and may become difficult to improve unless a precise diagnosis and treatment is
      not performed. Anxiety disorder and depressive state often merges the condition,
      and the patients with respiratory diseases sometimes may benefit from a
      antianxiety agents and antidepressant therapy when significant depressive
      symptoms are present. Specific psychotherapy may be applicable when symptom is
      aggravated by remarkable psychologic factors.

PMID- 22413498
TI  - [The use of psychotropic drugs for functional gastrointestinal disorders: are
      they beneficial?].
AB  - This article reviews the therapeutic role of psychotropic drugs in the treatment
      of functional gastrointestinal disorders based on the Japanese Diagnostic and
      Therapeutic Guidelines for Psychosomatic Disorders(2006). As an initial step,
      primary care physicians should establish a therapeutic relationship with their
      patients, provide instructions on diet or lifestyle modification, and treat them
      symptomatically. If these treatments are not satisfactory, as a next step, they
      should evaluate the patient's stressors, coping styles, and comorbid psychiatric
      disorders, especially anxiety disorders and depression, and prescribe
      psychotropic drugs such as antidepressants and anxiolytics. If these treatments
      are unsatisfactory, as a third step, physicians should refer their patients to
      psychosomatic medicine specialists to inquire about psychotherapy, hypnosis,
      fasting therapy, or relaxation training.

PMID- 22413499
TI  - [A psychotropic drug treatment of psychiatric symptoms after stroke].
AB  - Psychiatric syndromes are common in the patients with cerebrovascular disease.
      Poststroke depression (PSD) is a most frequent complication of after
      cerebrovascular disease. Depression affects 20-50% of patients within a year
      after stroke. PSD has a negative impact on functional recovery. Poststroke
      anxiety disorder, apathy and pathological laughing and crying are also frequent
      and under-detected symptoms. In this chapter, we described an outline mainly on
      treatment of PSD among these symptoms, in paticular, about antidepressant
      medications. There is an association between depression and atherosclerosis.
      Several trials have shown evidence that antidepressants may prevent depressive
      symptoms after stroke. The concept of "vascular depression" will suggest that the
      establishment of a new treatment strategy is demanded in future.

PMID- 22413500
TI  - [Neurodegenerative diseases].
AB  - Neurodegenerative diseases are characterized by pathological changes, neuronal
      loss and gliosis. These disease involved changes of neurotransmitter in central
      nervous system. In Alzheimer's disease, cholinergic neurons were depleted. In
      Parkinson's disease(PD), while several kinds of mediator were affected,
      dopaminergic neurons were mainly associated with motor and non-motor symptoms.
      Antipsychotic drugs may induce worsening of parkinsonism and neuroleptic
      malignant syndrome in PD and dementia Lewy bodies(DLB). Therefore, it is
      recommended to use atypical antipsychotic drugs, especially quetiapine, for
      treatment of psychosis in PD and DLB.

PMID- 22413501
TI  - [How to use of the psychotropic drug in rheumatic disease].
AB  - The role of antidepressants in relieving pain and depression in rheumatic
      diseases are not clear. Specifically, higher depression has been shown to be
      related to higher pain, higher fatigue, and reduced quality of life for persons
      with rheumatic disease. At first, treat steroid, immunosuppressive agent and
      disease modifying anti-rheumatoid drug for rheumatic disease. When depression
      state does not improve even it, psychotropic drug (e.g., antidepressant drug,
      anti-anxiety agent, sleeping drug, etc) is used if necessary.

PMID- 22413502
TI  - [Psychotropic medication in the patients with end-stage renal disease].
AB  - The majority of psychotropic drugs are well tolerated in the patients with end
      stage renal disease. There are exceptions for which tolerance and safety are
      questionable. These include psychotropic drugs such as milnacipran, sulpiride,
      lithium carbonate, memantine, gabapentin, pregabalin and topiramate.

PMID- 22413503
TI  - [Psychotropics in dermatology].
AB  - In dermatology, psychotropics are sometimes useful. But it is not still popular
      in clinical dermatology. It is recommended to use them for the patients who have
      psychosomatic aspect, anxiety and depression due to skin disease. Psychotropics
      are also useful to alleviate the sensation of itch. Trichotillomania and excess
      scratch are treated with antidepressants, anticonvulsants or antipsychotics.
      Cutaneous dysesthesia and delusional parasitosis are treated with antipsychotics.
      In prescribing benzodiazepines and hypnotics, we have to check abuse and
      dependency. Decrease of dosage should be made gradually. Antidepressants,
      anticonvulsants (except barbiturates) and antipsychotics have no dependency. They
      are much easily used than benzodiazepines. Drowsy and thirsty are main side
      effects that antihistamines also have. It should be noticed to use both
      simultaneously.

PMID- 22413504
TI  - [Application of antidepressant to treat patients in the department of
      otolaryngology].
AB  - There are some patients complaining of somatic symptom who has depression. The
      use of antidepressant to these patients would be quite useful. Patients with
      dispersion have a variety sort of physical symptom. The evaluation of depression
      based on physical complaints may be difficult for otorhinolaryngologists, but it
      is important to do so where possible to increase the focus on the subject's
      physical illness. The prevalence of somatic complaints in hospitalized patients
      whose chief complaint was either dizziness or vertigo was very high. These
      patients were usually accompanied with depression. Then the effect of paroxetine
      to the patients with tinnitus was investigated. The paroxetine may be effective
      in treating distressed tinnitus patients with depression and anxiety by reducing
      their tinnitus severity as well as their depression and anxiety.

PMID- 22413505
TI  - [Psychopharmacology and oral psychosomatic disorder].
AB  - It is uncommon to encounter patients presenting with medically and psychiatry
      unexplained oral symptoms like pain or discomfort. These symptoms have been
      called "oral psychosomatic disorders (OPSD)" in general. From a clinical point of
      view, OPSD may be due to several biochemical disorders involving
      neurotransmitters in the brain, incomplete connections between oral region and
      undefined complaints due to cognitive processes in higher centers of the brain.
      The main psychosomatic treatment is psychopharmacological therapy with
      antidepressants, including tricyclic antidepressants (TCAs), serotonin
      norepinephrine reuptake inhibitors(SNRIs), selective serotonin reuptake
      inhibitors(SSRIs), and other antidepressants (e.g., mirtazapine)". The proper use
      of these antidepressants is extremely important for the successful treatment of
      OPSD.

PMID- 22413506
TI  - [Pharmacological management of psychiatric disorders among cancer patients].
AB  - Approximately half of patients actually die from cancer even today, and many
      cancer patients require care for psychological distress. From the viewpoint of
      psychiatric diagnosis, the most common psychiatric conditions experienced by
      cancer patients are adjustment disorders, major depression, and delirium.
      Appropriate pharmacological treatment as well as psychotherapy and/or supportive
      intervention should be provided for cancer patients with these psychiatric
      disorders. Psychotropic medication including benzodiazepines, antidepressants,
      and major antipsychotics are usually provided depending on each patient's
      symptoms. This review focuses on the psychiatric disorders experienced by cancer
      patients and provides an overview regarding appropriate pharmacological
      interventions for psychiatric disorders among cancer patients.

PMID- 22413507
TI  - [Use of psychotropic agents for children with psychosomatic problems and
      developmental disorders].
AB  - A special consideration of psychotropic medication for children and adolescents
      in Japan is described. The use of all antidepressants and antianxiety drugs are
      "off-label". When using psychotropic drugs for the adolescents who complaint
      general fatigue, headache, or sleep disturbance, it should be confirmed the
      presence of the orthostatic disturbance (OD), because those drugs have the
      possibility of deteriorating the symptoms of OD. It is necessary to evaluate the
      risk and benefit for use of antidepressants in adolescents with major depression,
      considering the possibility of increasing suicide attempts. Long-acting
      methylphenidate and atomoxetine are regarded as the first line drugs for the
      treatment of children with attention deficit hyperactivity disorder. It is
      expected to solve "off-label" use and to establish clinical guidelines for the
      pharmacological treatment.

PMID- 22413508
TI  - [How to use psychotropic medicine in women].
AB  - It's very important to know how to use psychotropic medicine, especially
      selective serotonin reuptake inhibitors in pregnant women. Because between 14%
      and 23% of pregnant women will experience a depressive disorder while pregnant.
      In 2003, approximately 13% of women took an antidepressant at some point in
      pregnancy, a rate that has doubled since 1999. Both maternal depressive symptoms
      and antidepressant exposure are associated with fetal growth changes and shorter
      gestations, but the majority of studies that evaluated antidepressant risks were
      unable to control for the possible effects of a depressive disorder.
      Antidepressant use in pregnancy is well studied, but available research has not
      yet adequately controlled for other factors that may influence birth outcomes
      including maternal illness or problematic health behaviors that can adversely
      affect pregnancy.

PMID- 22413509
TI  - [Psychotropic medication of elderly patients].
AB  - Drugs medicated for elderly patients show different pharmacokinetics from young
      patients, because of change in the makeup of bodies, decrease of albumin,
      increase of alpha-1-acid glycoprotein, hypofunction of metabolism, and excretion
      by aging. In addition, complications or other concomitant drugs influence their
      pharmacokinetics. Therefore, when we take medication for elderly patients, we
      need consideration different from young patients. Psychiatric symptoms which
      frequently occurred in elderly patients are dementia (including behavioral and
      psychological symptoms of dementia), depressive state, sleep disturbance, and
      delirium. As warned by Food and Drug Administration, some studies reported that
      using antipsychotics for elderly patients with dementia increase their death
      rate. We have to give informed consent sufficiently to patients and their
      families.

PMID- 22413510
TI  - [Cephalic hypersensitivity syndrome].
AB  - The number of patients suffering from chronic headache accompanied by dizziness
      and cephalic ringing is gradually increasing. Pathophysiology of migraine has
      been commonly explained by trigeminovascular theory, although recent studies have
      suggested that the cause of the migraine stems from cortical hyperexcitability.
      We measured EEG in 1,000 patients suffering from daily headache accompanied by
      dizziness and cephalic ringing. Here we defined a new syndrome,"cephalic
      hypersensitivity syndrome" as a subliminal cortical hyperexcitability which
      itself is invisible but apparently seen as some symptoms such as dizziness and
      cephalic ringing. The cephalic hypersensitivity syndrome should be treated to
      attenuate the excitability by an appropriate triptan medication during attacks so
      as to exhibit its recurrence.

PMID- 22413511
TI  - [Mental disorder and suicide prevention in patients with physical illness].
AB  - Suicide rate in Japan is 25/100,000 in a year. The rate is higher than those in
      other developed countries. Physical illness is a risk factor for suicide. To
      prevent suicide in patients with physical illness, identification of mental
      illness, such as depression, is important. In addition, palliative care for
      distressing physical and psychological symptoms is also important. In process of
      identification of mental illness and distressing physical symptoms,
      communications between medical staff and patients are essential. Enhancing
      communication skills of medical staff may be a key point to prevent suicide.

PMID- 22413512
TI  - [Novel strategies that target hepatokines for treatment of type 2 diabetes].
AB  - The liver may maintain systemic homeostasis by releasing secretory proteins into
      the blood stream. In fact, comprehensive gene expression analysis revealed that
      the liver in humans expresses various kinds of genes encoding secretory proteins.
      Recently, function-unknown liver-derived secretory proteins have been termed as
      hepatokines. Using comprehensive gene expression analyses, we have identified
      selenoprotein P(SeP) as a novel hepatokine that elevates plasma glucose levels by
      inducing insulin resistance. RNA interference-mediated knockdown of SeP in the
      liver improved insulin resistance and hyperglycemia in type 2 diabetic mice,
      suggesting that SeP is a novel therapeutic target for type 2 diabetes. Further
      functional characterization of hepatokines might provide novel diagnostic and
      therapeutic targets for the other diseases except diabetes.

PMID- 22413513
TI  - [Antidiabetic fixed-dose combination tablet for the management of type 2
      diabetes].
AB  - How to use oral antidiabetic fixed-dose combination tablet for the management of
      type 2 diabetes (T2DM)? In addition to diet and exercise, the majority of
      diabetic patients need drug therapy to achieve optimal glycemic control.
      Monotherapy with oral antidiabetic agent is the firstline pharmacologic treatment
      option. However, in order to maintain glycemic control, additional oral
      antidiabetic agents are often added to monotherapies resulting in dual therapy.
      Dual therapy can be prescribed as separate pills, or as a single pill containing
      two agents. Randomized controlled trials of patients requiring dual therapy, have
      shown fixed-dose combination therapies to have superior efficacy when compared to
      loose-pills combination therapies. T2DM patients treated with fixed-dose
      combination therapies may have better adherence, improved satisfaction, and lower
      direct costs, compared to those treated with loose-pill combination therapies.

PMID- 22413514
TI  - [Acquisition of resistance mechanism in multidrug resistant organisms].

PMID- 22413515
TI  - [Current trend in bacterial acquisition of multiple drug resistance].

PMID- 22413516
TI  - [Three months survey of multidrug-resistant Enterobacteriaceae in Japan].
AB  - In 2010, a three months survey of multidrug-resistant Enterobacteriaceae was
      conducted by Ministry of Health, Labour and Welfare of Japan. A total of 153
      isolates were obtained through this survey and we performed PCR using the NDM-1
      type, KPC type, IMP-1 type, IMP-2 type and VIM-2 type carbapenemase genes
      specific primers. Of 153 analyzed isolates, 72 (47.1%) were positive for IMP-1
      type bla(IMP), and two isolates from two patients were positive for bla(NDM-1).
      None of those patients had traveled abroad. Two isolates from a single patient
      who had traveled and hospitalized in abroad were positive for bla(KPC). 77
      (50.3%) isolates were all negative for those five carbapenemase genes. It was
      shown that IMP-1 type is the most predominant carbapenemase gene among
      Enterobacteriaceae in Japan.

PMID- 22413517
TI  - [Clinical and social problems in controlling multidrug-resistant organisms].
AB  - There have been limited evidence for controlling multidrug-resistant Gram
      negative bacilli, since multidrug-resistant Pseudomonas aeruginosa (MDRP) and
      multidrug-resistant Acinetobacter baumannii (MDR-Ab) have emerged. The Center for
      Disease Control and Prevention (CDC) has published the first guideline entitled
      'Management of Multidrug-Resistant Organisms in Healthcare Settings, 2006'.
      Following that, the Association for Professionals in Infection Control and
      Epidemiology (APIC) has also published a guidance entitled 'Guide to the
      Elimination of Multidrug-resistant Acinetobacter baumannii Transmission in
      Healthcare Settings' in 2010. The Japanese Society for Environmental Infections
      (JSEI) has launched soon after the largest MDR-Ab outbreak was reported, and then
      published the position statement on controlling multidrug-resistant organisms.
      The aim of this statement is to provide a clear direction of controlling
      multidrug-resistant Gram negative bacilli to Japanese healthcare facilities, when
      planning a grand design of infection control in each setting. In this report,
      critical points and matters need to be discussed were assessed.

PMID- 22413518
TI  - [Molecular epidemiology of multidrug-resistant organisms].
AB  - Recent advance in molecular epidemiology of multidrug-resistant organisms (MDROs)
      was described. Most of MDROs are spreading over the world in a short period,
      monitoring of certain epidemic strains of MDROs is very important. Since Cantor
      et al. developed pulsed-field gel electrophoresis (PFGE) in 1984, genotyping
      tools became major tools for laboratory based-epidemiologic analysis. Recent
      advance was developed by two major technologies. One is multilocus sequence
      typing (MLST) and the other one is matrix assisted laser desorption ionization
      time of flight-mass spectrometry (MALDI-TOF-MS). MALDI-TOF-MS technology is still
      under developing, but near future it will become major tools for MDROs molecular
      epidemiology.

PMID- 22413519
TI  - [Staphylococcus aureus (methicillin-resistant S. aureus: MRSA)].
AB  - Before antibiotic development, Staphylococcus aureus was a cause of serious
      invasive infections such as sepsis and meningitis and claimed many lives.
      However, even after antibiotic development, S. aureus posed a new threat as a
      major nosocomial pathogen, changing it to methicillin-resistant S. aureus (MRSA)
      since 1961. This year marks the 50th anniversary of the first report on MRSA.
      Today, there are two classes of MRSA spreading in hospitals and the community.
      The United States experienced invasive MRSA epidemics in 2005, and the latter
      MRSA (named CA-MRSA), especially USA300, affected the entire United States. As a
      countermeasure, guidelines for the management of MRSA infections were prepared in
      2011. In Japan, there are people who are suffering from "hidden" epidemics in the
      community, falling behind in fighting CA-MRSA. We summarized current epidemic
      MRSA and infections.

PMID- 22413520
TI  - [Enterococcus].
AB  - Enterococci have a variety of intrinsic antibiotic resistances, and also they can
      acquire new antibiotic resistance determinants including mutated ligase genes
      such as VanA or VanB. The increased prevalence and dissemination of multidrug
      resistant Enterococci (i.e., Vancomycin resistant Enterococci: VRE) worldwide
      have resulted in a major decrease in therapeutic options and poor prognosis of
      infections by these organisms. Newer antibiotics, linezolid, Q/D, daptomycin and
      tigecycline have good in vitro activity against, however their clinical use are
      limited in certain infectious diseases. Although the prevalence of VRE in Japan
      is still quite low, strict infection control measures including active
      surveillance and regional information sharing is necessary to prevent
      dissemination in hospitals and regions.

PMID- 22413521
TI  - [Streptococcus pneumoniae infection and drug resistance in Japan].
AB  - In Japan, 7-valent pneumococcal conjugate vaccine was introduced in 2010. The
      population-based survey of invasive infection in child revealed that 62.7% of the
      S. pneumoniae isolates showed equal or more than 0.125 microg/mL of penicillin G
      MIC. ST320 with serotype 19A S. pneumoniae isolates showed 2-4 microg/mL and 0.25
      0.5 microg/mL MICs of penicillin G and meropenem, respectively. The early
      introduction of PCV13 in Japan is anticipated.

PMID- 22413522
TI  - [Current situations and countermeasures regarding antimicrobial resistance in
      group B streptococcal isolates from patients, ranging from newborn to the
      elderly, with invasive infections].
AB  - Several group B streptococci (GBS) strains resistant to macrolides, lyncomycins,
      fluoroquinolones, or tetracyclines, are reported in isolates from children or
      adults patients with invasive infections. Some strains with reduced
      susceptibility to beta-lactams also are observed among subjects with invasive or
      noninvasive diseases. Constitutively expressed erm methylase gene confers
      resistance to both macrolides and lyncomycins, while the tetM gene carried on
      transposon Tn916 contributes to tetracycline resistance. Significant amino acid
      substitutions (GyrA, Ser81Leu; ParC, Ser79Phe) in topoisomerases induce
      resistance to fluoroquinolones, and other substitutions (PBP2X, Gln557Glu and
      Val405Ala; PBP2B, Gly613Arg) adjacent to significant motifs in penicillin-binding
      proteins produce decreased beta-lactam susceptibility. Therefore, current
      interventions concerning prophylaxis and treatment will need to re-evaluate in
      future.

PMID- 22413523
TI  - [Multidrug-resistant Pseudomonas aeruginosa T].
AB  - The emergence of Pseudomonas aeruginosa strains resistant to carbapenems,
      fluoroquinolones and amikacin, which were defined as multidrug-resistant (MDR)
      strains, is a serious problem in Japan. Nosocomial outbreaks of MDR P. aeruginosa
      infection have become problematic in hospitals. The percentage of MDR isolates at
      medical facilities was about 2.5% of P. aeruginosa isolates. Furthermore, clonal
      expansion of P. aeruginosa strains highly resistant to these antibiotics with
      MICs of more than 64 microg/mL occurred in community hospitals. Most of these
      multidrug highly resistant strains produced metallo-beta-lactamase IMP-1 and
      aminoglycoside 6'-N-acetyltransferase AAC(6')-Iae. An immunochromatographic assay
      was developed for the rapid detection of these enzymes producing strains. The
      developed assay is an easy-to-use and reliable detection method for the multidrug
      highly resistant P. aeruginosa.

PMID- 22413524
TI  - [Acinetobacter spp].
AB  - Acinetobacter species are aerobic, glucose non-fermenting gram-negative rods, and
      ubiquitous in the environment. Acinetobacter spp. can survive for months on dry
      surfaces. Acinetobacter spp. have been grown from skin, pharynx, sputum, urine
      and feces. The most common Acinetobacter infection is pneumonia. According to
      Japan Nosocomial Infection Surveillance, 0.34% of the Acinetobacter spp. was
      multidrug-resistant in 2010. In Japan, Acinetobacter spp. whose imipenem MICs
      were > or = 16 microg/mL, amikacin > or = 32 microg/mL, and ciprofloxacin > or =
      4 microg/mL were defined as multidrug-resistant Acinetobacter species (MDRA) in
      2011 in the amended Infectious Diseases Control Law. Break-point Checkerboard
      Plate can help to infer an effective combination antimicrobial therapy. A
      selective medium for the isolation of MDRA is a great tool for active
      surveillance cultures. Treatment options for MDRA infections in Japan are very
      limited, because colistin, polymyxin B, or tigecycline is not approved. Keys to
      control MDRA are high levels of compliance with standard and contact precautions,
      appropriate cleaning and disinfection of the environment, and judicious
      antimicrobial use.

PMID- 22413525
TI  - [Mycobacterium tuberculosis].
AB  - The emergence and spread of multidrug-resistant (MDR) and extensively drug
      resistant (XDR) tuberculosis (TB) has become an important health problem and
      threatens TB control worldwide. World Health Organization reported that there
      were an estimated 440,000 cases of MDR-TB in 2008. By July 2010, 58 countries and
      territories had reported at least one case of XDR-TB. The emergence of MDR/XDR-TB
      strains is reflection of poor tuberculosis management. To avoid the emergence of
      more resistant strains that may lead to almost untreatable TB, we must focus our
      efforts on the right management of drug susceptible TB.

PMID- 22413526
TI  - [Mechanisms of beta-lactam and quinolone resistance in Haemophilus influenzae].
AB  - Haemophilus influenzae is one of the important pathogens causing respiratory
      tract infections, pneumonia, and meningitis. Genotypic(g) beta-lactamase
      nonproducing ampicillin resistance (gBLNAR) H. influenzae has rapidly increased
      since 2000 years in Japan. The resistant percentage exceeded 60% in Hib isolates
      from meningitis in 2009. The affinity of beta-lactam antibiotics for penicillin
      binding proteins-3 (PBP3) that involved in septal peptidoglycan synthesis
      deceased in the resistant strains. Three amino acid substitutions, Ser385Thr,
      Asn526Lys and Arg517His in PBP3 encoded by ftsI gene are especially responsible
      for beta-lactam resistance in the gBLNAR. Susceptibilities of cephalosporin
      agents including cefotaxime for gBLNAR were apparently decreased than the
      ampicillin and carbapenem antibiotics. Though fluoroquinolone resistant isolates
      are rare (< 1%) in H. influenzae, strains of levofloxacin and ciprofloxacin MIC
      with > or = 8 microg/mL were isolated from elderly patients with CAP. These
      strains possessed amino acid substitutions of Ser84Phe and Asp88Asn in GyrA and
      Glu88Lys in ParC. It is important to practice rapidly identification of these
      resistant strains at routine work.

PMID- 22413527
TI  - [Macrolide-resistant Mycoplasma pneumoniae].
AB  - Mycoplasma pneumoniae (M. pn) is one of the main pathogens causing community
      acquired pneumonia (CAP) in children. In Japan, macrolide (ML)-resistant M. pn
      was firstly isolated from clinical samples collected from pediatric patients with
      CAP in 2000, and the agents have rapidly increased. All ML-resistant strains had
      a point mutation in domain V of the 23S rRNA. Among the patients with ML
      resistant M. pn, the duration of fever was significantly longer than in patients
      with ML-susceptible M. pn infection. The antimicrobial agent was often changed
      from ML as a first choice agent to minocycline or levofloxacin, because of
      unimproved clinical symptoms. Further clinical studies are needed to establish
      appropriate chemotherapy.

PMID- 22413528
TI  - [ESBL producing organisms].
AB  - The isolation frequency of extended-spectrum beta-lactamase (ESBL) producing
      organisms, especially CTX-M-15 producing Escherichia coli, is increasing
      worldwide. The predominant ESBL producing E. coli epidemic clone in humans is
      O25b: H4-ST131. ESBL producers are isolated not only from infected patients but
      also healthy humans, domestic animals, foods and the environment. However few
      E.coli ST131 clone are isolated from domestic animals or foods. Futhermore CTX-M
      1 or CTX-M-9 is the predominant subgroups found in human whereas the CTX-M-2
      subgroup is the predominant ESBL isolated from non-human samples. Accordingly,
      there is no direct evidence of spread of ESBL producers between humans and
      domestic animals or foods.

PMID- 22413529
TI  - [New Delhi metallo -beta-lactamase-1 (NDM-1) producing bacteria].
AB  - New Delhi metallo-beta-lactamase-1 (NDM-1) producing organisms are now becoming
      highly prevalent worldwide. We detected first two Japanese cases infected by
      Escherichia coli in Dokkyo Medical University Hospital and Klebsiella pneumoniae
      in Saitama Citizen Medical Center. These two NDM-1-producing bacteria are
      resistant to multiple antibiotic drugs including carbapenems, aminoglycosides,
      and fluoroquinolones. The genetic analysis showed that these two bacteria
      possessed different NDM-1 plasmids. Although the patient with E. coli had
      previously been treated in India, MLST typing showed that these bacteria are
      distinct from the reported ST clones elsewhere in the world. These results
      suggest that NDM-1 plasmids are highly variable and transferable to wide-range
      organisms. We warrant rigorous surveillance and strict infection control.

PMID- 22413530
TI  - [KPC carbapenemase producing Gram-negative bacteria].
AB  - Carbapenem is the last resort for infections due to Gram-negative bacteria.
      However, carbapenem-resistant Enterobacteriaceae such as KPC-producing bugs were
      reported in the United States from early this decade and now worldwide. According
      to the nationwide surveillance study in Japan performed between September and
      December, 2010, two bla(KPC)-harboring Klebsiella pneumoniae were identified
      among 153 multi-drug-resistant Enterobacteriaceae. Moreover, 72 out of 153 multi
      drug-resistant Enterobacteriaceae harbored bla(IMP-1). The results of this
      surveillance study demonstrated that the most epidemic carbapenemase in Japan is
      not bla(KPC) but bla(LMP-1). Although the bla(KPC)-harboring strain is very rare
      in Japan, detection of KPC-producing Gram-negative bacteria may be difficult
      based on the CLSI recommended method. Development of effective screening methods
      is needed in the Japanese healthcare environment.

PMID- 22413531
TI  - [Antimicrobial resistance testing in clinical practice].
AB  - Previously unrecognized or underrecognized antimicrobial resistant bacteria,
      including NDM-1-producing Enterobacteriaceae and multidrug-resistant
      Acinetobacter baumannii, were recently identified in health care facilities in
      Japan. Vigilance in the clinical microbiology laboratory for these organisms is
      the key to early recognition of their emergence. Many of these organisms can be
      confirmed or at least suspected through routine susceptibility testing, which can
      then be referred to reference laboratories for further phenotypic or genetic
      testing. Antimicrobial resistance testing plays a crucial role in patient
      management, infection control and monitoring of local as well as national and
      international epidemiology.

PMID- 22413532
TI  - [Current state of susceptibility test in Japan].
AB  - Susceptibility test is important, because it is the significance of definitive
      therapy, infection control and prevention. In fact, drug resistant bacteria are
      found in susceptibility test, screening test and confirmed test are needed.
      Recently, in Japan many laboratories are using criteria of CLSI standard. In this
      time, we explain the current state of susceptibility test in Japan.

PMID- 22413533
TI  - [Molecular analysis of the antimicrobial resistant bacteria].
AB  - The antimicrobial susceptibility test is generally performed in clinical
      laboratories for detecting antimicrobial resistant bacteria. In contrast, the
      molecular tests include many investigative factors, they are not performed in
      many clinical laboratories routinely. If it is intimately related to the choice
      of the antimicrobial agents, it should be introduced as a routine clinical
      laboratory test. This test is also useful for conducting active surveillance and
      investigating the cause and occurrence of nosocomial infections.

PMID- 22413534
TI  - [Isolation precautions--transmission-based precautions].
AB  - There are two tiers of precautions to prevent transmission of infectious agents,
      standard precautions and transmission-based precautions. Standard precautions are
      intended to be applied to the care of all patients in all healthcare settings,
      regardless of the suspected or confirmed presence of an infectious agent.
      Transmission-based precautions are for patients who are known or suspected to be
      infected or colonized with infectious agents, which require additional control
      measures to effectively prevent transmission. Transmission-based precautions are
      used empirically, according to the likely etiologic agents at the time, and then
      modified when the pathogen is identified or a transmissible infectious etiology
      is ruled out. Implementation of preventive measures should be based on infection
      control risk assessment.

PMID- 22413535
TI  - [Antimicrobial stewardship].
AB  - The purpose of the antimicrobial stewardship is to make an effort so that it
      tries to draw out the maximum effect by using the antimicrobial agent and to
      decrease the risk of side-effect, and suppress the emergence of antimicrobial
      resistant organisms. Antimicrobial stewardship is an activity to achieve these
      goals. Antimicrobial stewardship must be regarded as quality control and risk
      management procedure in the medical institution. Enough authorization to medical
      staff by the executive of the hospital is indispensable for the achievement of
      proper use of antimicrobial agents. Additionally, the manager of the hospital
      should give enough resources to support this activity.

PMID- 22413536
TI  - [Combination therapy against multidrug-resistant bacteria].
AB  - The purpose of antibiotic combination therapy includes two points, as follows; 1)
      expectation of synergistic effects, 2) preventing the emergence of drug-resistant
      bacteria following exposure to antibiotics. Synergism has been shown in vitro for
      many antibiotic combinations and bacterial species, but it is uncertain whether
      synergistic effects in vitro are applicable to the clinical setting and lead to a
      better prognosis. beta-lactam and aminoglycoside combinations have synergistic
      effects against Gram-negative bacteria, including Pseudomonas aeruginosa,
      Klebsiella, Escherichia coli, and other Enterobacteriaceae in vitro; however,
      combination therapy is not considered for these pathogens routinely in vivo.
      Multidrug-resistant (MDR) pathogens have emerged as increasingly problematic
      causes of hospital-acquired infection. When MDR Gram-negative bacillary infection
      occurs in immunocompromised patients, combination therapy is considered. In
      Japan, MDR P. aeruginosa is becoming a serious problem in the clinical setting.
      Here, we present an antibiotic combination therapeutic strategy against MDR P.
      aeruginosa infection.

PMID- 22413537
TI  - [Polymyxin B hemoperfusion (PMX-F) for severe sepsis and septic shock].
AB  - PMX-F, which was developed in Japan, is a potential therapeutic option for severe
      sepsis and septic shock. Despite positive effects on surrogate outcomes,
      demonstrated in methodologically suboptimal preliminary studies, its benefit on
      mortality remains unclear. Surprisingly, this expensive investigational therapy
      has been reimbursed by the Japanese National Health Insurance program since 1994
      and 75,000 cartridges have been consumed, sometimes without expert intensive care
      supervision. Current evidence in intensive care medicine does not justify
      utilizing PMX-F for severe sepsis and septic shock, considering its unproven
      benefit, significant cost and potential risks. Even if reduced mortality is shown
      in future studies, that benefit could easily be cancelled out in settings, such
      as many Japanese institutions, where intensive care expertise is unavailable.

PMID- 22413538
TI  - [Development status of new antibacterials].
AB  - The increase of the infections caused by multi-drug-resistant bacteria is a
      serious problem worldwide. As for Gram-positive bacteria, the community-acquired
      methicillin-resistant Staphylococcus aureus and vancomycin- or linezolid
      resistant strains have been increasing. As for Gram-negative bacteria, multi-drug
      resistant strains of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter
      baumannii have been increasing due to the carbapenemase production recently.
      During these 10 years, various types of novel antibacterials targeted for Gram
      positive bacteria have been approved in US and EU, but not in Japan. On the other
      hand, the discovery of new antibacterials targeted for Gram-negative bacteria is
      still immature. In this review, the status of the discovery of new antibacterials
      targeted for these multi-drug-resistant bacteria will be reviewed.

PMID- 22413539
TI  - [The managements of nosocomial outbreaks of multi-drug resistant bacteria].
AB  - Hospital outbreaks of multi-drug resistant bacteria have been reported in a
      number of contexts, particularly in areas where seriously ill patients are
      treated, for example in intensive care units sometimes with spread to other
      wards. When the serious outbreak occurs, the hospital had better to make official
      announcement and receive third-party assessment. The local network for
      consultation is also recommended by Japanese Ministry of Health, Labor and
      Welfare. The outbreaks of multi-drug resistant pathogens are easily recognized,
      but surrounding the outbreaks, numerous numbers of drug sensitive bacterial
      outbreaks must occur in obscurity. Then the concept of "never events" should be
      spread for prevent nosocomial infections, also in Japan.

PMID- 22413540
TI  - [Travellers and multi-drug resistance bacteria].
AB  - The number of international travellers has increased. There is enormous diversity
      in medical backgrounds, purposes of travel, and travelling styles among
      travellers. Travellers are hospitalized abroad because of exotic and common
      diseases via medical tourism. This is one way of transporting and importing human
      bacteria between countries, including multi-drug resistant organisms. In
      developing countries, the antimicrobial resistance in Shigella sp. and Salmonella
      sp. have been a problem, because of this trend, the first choice of antibiotics
      has changed in some countries. Community acquired infections as well as hospital
      acquired infections with MRSA, multi-drug resistance (MDR) Pseudomonas
      aeruginosa, and ESBL have been a problem. This review will discuss the risk of
      MDR bacterial infectious diseases for travellers.

PMID- 22413541
TI  - [Genetic elements involved in the acquisition of antimicrobial resistance genes
      in bacteria].
AB  - A variety of genetic elements play key role in the dissemination of antimicrobial
      resistance genes among gram-negative bacteria. Transposons can transfer
      resistance genes intracellularly, while conjugative plasmids carrying resistance
      genes can move from one bacterial cell to another. Integrons are genetic elements
      that can collect several resistance genes in the form of gene cassettes. These
      genetic elements sometimes coexist and work cooperatively. For example,
      integrons, which is not mobile by themselves, can obtain an ability to transfer
      when they are incorporated into transposons. Recent reports suggest that
      integrative and conjugative elements, hybrid elements of conjugative plasmids and
      phages, also contribute to the dissemination of resistance genes among gram
      negative bacteria.

PMID- 22413542
TI  - [New mechanisms of quinolone resistance among Enterobacteriaceae: focused on
      plasmid-mediated quinolone resistance].
AB  - Quinolones are useful synthetic antimicrobial agents in the clinical settings
      with broad specrum, potent efficacy, good bioavailability, and excellent safety.
      Therefore, development and increase of quinolone-resistance among clinically
      isolated pathogens are a worrisome problem. Recently, increasing numbers of
      plasmid-mediated quinolone resistance (PMQR) among clinical isolates of
      Enterobacteriaceae have been reported. PMQR consists of Qnr family as a
      protective determinant of bacterial drug-target enzymes, Aac (6')-Ib-cr as a drug
      modifying enzyme, and plasmid-mediated quinolone efflux pumps. In this review,
      biological features of PMQR determinants including discovery, phylogeny and
      presumable physiological role, as well as their clinical contribution of the
      acquisition and development of quinolone resistance, are discussed.

PMID- 22413543
TI  - [Circadian rhythm abnormality and hypertension].
AB  - In our consumer-oriented society, poor sleep patterns and hectic lifestyle are
      detrimental to harmonious physiological and metabolic body systems, with severe
      impact on public health. Circadian rhythms generated by a trillion peripheral
      cellular clocks throughout the body, governing most aspects of human physiology
      and behavior, are threatened to be compromised. We recently reported that
      arrhythmic mice lacking the clock genes Cry1 and Cry2(Cry-null mice) show salt
      sensitive hypertension due to abnormally high synthesis of the mineralocorticoid
      aldosterone in the zoma glomerulosa of the adrenal gland. The clock-controlled
      enzyme, a new type 3beta-hydroxyl-steroid dehydrogenase, is claimed to be a
      possible cause of hypertension.

PMID- 22413545
TI  - [How we stop the decrease of surgeons?].

PMID- 22413544
TI  - [Melatonin agonist: a possible disease-modifying agent for Alzheimer's disease].
AB  - Recent advance of therapeutic intervention makes immunotherapies disease
      modifying therapy for Alzheimer's disease. Several lines of evidence indicated
      that melatonin or indole structures are candidates for disease-modifying agents
      in Alzheimer's disease. We herein reviewed the in vivo efficacy of melatonin in a
      transgenic model of Alzheimer's disease and discuss about a potential of
      melatonin agonist for treating Alzheimer's disease.

PMID- 22413546
TI  - [To improve work environment of Japanese surgeons].

PMID- 22413547
TI  - [Recent progress in the treatment of advanced gastric cancer].

PMID- 22413548
TI  - [Standard strategy for lymph node dissection in advanced gastric cancer
      patients].
AB  - The standard strategy for lymph node dissection in advanced gastric cancer
      patients is defined as D2 lymph node dissection based on the Japanese
      Classification of Gastric Cancer and Gastric Cancer Treatment Guidelines 2010
      edited by the Japanese Gastric Cancer Association. Lymph nodes that should be
      dissected for D2 are also defined according to whether the surgical method is
      total gastrectomy or distal gastrectomy. The locations of those lymph nodes are
      anatomically described in the Japanese Classification of Gastric Cancer: No. 1 to
      12. The efficacy of prophylactic extended lymph node dissection in the paraaortic
      area (No. 16) was not confirmed in a randomized clinical trial (JCOG9501).
      Splenectomy aiming for complete lymph node dissection at the splenic hilum is
      under evaluation in a clinical trial (JCOG0110). Optional dissection of the lower
      mediastinal lymph nodes (No. 110, 111) is recommended for junctional tumors,
      although the dissection of lymph nodes at the root of the supramesenteric vein
      (No. 14v) and behind the pancreas (No. 13) remains controversial.

PMID- 22413549
TI  - [Adjuvant therapy for advanced gastric cancer].
AB  - The importance of surgery (gastrectomy plus lymph node dissection) for the
      treatment of advanced gastric cancer is unquestionable, although there has been a
      disparity in methods used to achieve local control in Asia and the West. The
      superiority of D2 dissection has not been confirmed in a large multiinstitutional
      trial, and the long-term follow-up results of a Dutch trial revealed that the
      recurrence rate was lower in the D2 group. Thus, the European Society for Medical
      Oncology and the US National Comprehensive Cancer Network guidelines recommend D2
      dissection, leading to a worldwide consensus. Meanwhile, the focus of oncology
      should be on multimodality treatment for cure, and numerous large, randomized
      clinical trials have established effective adjuvant treatment. In gastric cancer,
      different evidence emerged first in the USA, followed by Europe, and Japan/the
      Republic of Korea to become the standard for each: adjuvant chemoradiation,
      perioperative adjuvant chemotherapy, and postoperative chemotherapy,
      respectively. The Japanese standard has become adjuvant S-1 chemotherapy for 1
      year after surgery, and the optimal regimen for stage III should be further
      investigated in consideration of other robust results. Other issues include the
      role of surgery in local control with regard to adjuvant treatment such as
      radiation and molecular-targeted treatment to establish a worldwide standard.

PMID- 22413550
TI  - [Improving the quality of life after gastrectomy is the next issue after saving
      the lives of patients with gastric cancer].
AB  - Gastrectomy saves the lives of many patients with gastric cancer. However, this
      surgical treatment is associated with clinical problems called postgastrectomy
      syndrome (PGS) which affect the quality of life (QOL) of such patients. For
      surgeons, improving the QOL after gastrectomy is an important goal after
      performing curative surgery. In the clinical setting, various surgical procedures
      such as limited resection, function-preserving procedures, and reconstruction
      using gastric substitutes have been advocated to reduce the severity of PGS.
      However, the actual conditions and pathophysiology of PGS have not been fully
      investigated. Various clinical studies and basic research have partially
      clarified the features and pathophysiology of PGS, although the strategies
      developed to treat PGS have been limited. The development of standardized,
      reliable instruments for understanding PGS and performing large-scale
      collaborative studies are required to improve the diagnosis and treatment of PGS.
      In Japan, such a project called the PGSAS has recently been completed. The
      results are being analyzed and will be reported in the near future.

PMID- 22413551
TI  - [The updated treatment strategy for gastric cancer with peritoneal metastasis].
AB  - The standard of care for gastric cancer with peritoneal metastasis is
      chemotherapy. However, there is no chemotherapy regimen with a sufficient level
      of evidence, and thus S-1 plus cisplatin (CDDP), which is regarded as the
      standard regimen for advanced metastatic gastric cancer, is widely applied.
      Meanwhile the efficacy of intraperitoneal (IP) administration of taxanes has been
      verified, and the novel multidisciplinary treatment combining chemotherapy and
      surgery is now being tested. We developed a combination chemotherapy regimen of S
      1, weekly intravenous and IP paclitaxel (PTX), and determined the recommended
      dose of IP PTX to be 20 mg/m2 in our phase I study. In our phase II study, the
      median survival time (MST) of 40 patients enrolled was 23.6 months, and
      peritoneal cytology turned negative for 86% of 28 patients. Moreover, we
      performed gastrectomy on 52 patients after disappearance or obvious shrinkage of
      peritoneal metastasis, and the MST was 34.9 months. The multidisciplinary
      treatment combining IP-containing chemotherapy and surgery is safe and effective
      for gastric cancer patients with peritoneal metastasis. We have just started a
      phase III trial (PHOENIX-GC trial) comparing our IP regimen versus S-1 plus CDDP.

PMID- 22413552
TI  - [Treatment strategy for liver metastasis from gastric cancer].
AB  - Chemotherapy is the standard of care for gastric cancer patients with liver
      metastasis. Due to the paucity of hard evidence, other treatment modalities are
      not mentioned in the Japanese treatment guidelines for gastric cancer. However,
      some case series suggest that carefully selected patients may benefit from local
      treatment such as hepatectomy, radiofrequency ablation, and hepatic arterial
      infusion. The indications for local treatment and optimal method to combine it
      with systemic chemotherapy are discussed based on the information currently
      available.

PMID- 22413553
TI  - [Treatment of advanced gastric cancer in the elderly].
AB  - Because the aging process varies among individuals, elderly people of the same
      age, especially those over 80 years, do not necessarily have similar organ
      function. After consideration of lower organ function and concomitant disease,
      less invasive treatment should be selected for elderly patients. Therefore, it is
      important to limit preventive lymph node dissection, and when determining the
      dose of anticancer drugs, major organ function should be taken into
      consideration.

PMID- 22413554
TI  - [Management and treatment of perioperative infection].

PMID- 22413555
TI  - [Standard perioperative management to prevent postoperative infections].

PMID- 22413557
TI  - [Laparoscopic right hepatectomy--tips and pitfalls].

PMID- 22413556
TI  - [What we can learn from a case of medical malpractice--Nurse on duty exempted
      from the obligation to pay compensation because the use of restraining mittens to
      strap the upper limbs of the patient to the bed did not constitute a breach of
      contractual obligation].

PMID- 22413558
TI  - [Observation report about education of mid-level provider in US--education of PA
      in Samuel Merritt University and NP in University California, San Francisco].

PMID- 22413559
TI  - [Can female surgeons manage to work and raise their children at the same time, if
      the system of the child support is developed?].

PMID- 22413560
TI  - [A case of complex (type IV) paraesophageal hiatal hernia with herniation of the
      small intestine].
AB  - A 78-year-old woman was admitted to our hospital because of abdominal pain. She
      was diagnosed with complex (type IV) paraesophageal hiatal hernia, for which an
      operation was performed. At laparotomy, a 50 cm long ileum was found to have
      herniated into the thoracic cavity through the esophageal hiatus along with the
      sliding hiatal hernia of the stomach. Both the organs were reduced to the
      abdominal cavity. The hiatal hernia defect (diameter, 7cm) was repaired with a
      direct suture, and the gastric fundus was sutured to the diaphragm. Presently, 6
      years have passed since the operation, there is no sign of recurrence.

PMID- 22413561
TI  - Mental health and emotional relationships of family members whose relatives have
      drug problems.
AB  - The presence of a drug abuser in a family can seriously affect the family's
      mental health and relationships. This study focuses on the stress of families of
      drug abusers, relationships, and their relevant factors, as well as examines ways
      to support them. The subjects of this study were family members of drug abusers
      treated at drug abuser family support groups, medical institutions, or municipal
      mental health and welfare centers. To these institutions, 1,298 questionnaires
      were sent, and 543 responses with sufficient data were used for analysis. The
      survey consisted of the 12-item General Health Questionnaire (GHQ-12), and
      questionnaire items regarding disruptions to family life, relationship with drug
      users, and the use of family support services. The survey results showed that the
      mean GHQ score was 4.5, and those whose score are cut-off 3 and more, indicating
      poor mental health accounted for 54.7%. More than half of the subjects responded
      that drug problems have affected family members in terms of the health condition,
      daily living, and financial problems. Regarding emotional relationships with the
      addicts, most of the families answered that they have had negative feelings
      toward them, such as "being dragged into drug problems" and "being over
      protective". A significant correlation was observed between the GHQ score and
      family members' relationship with the addict, and these variables were closely
      correlated with participation in the family group, the status of drug abstinence,
      living environment, and participation in a self-support group by the addict. As
      the results, most of the family members of drug users have problems with mental
      health and the recovery of relationships even though they have accessed support
      centers, and it was verified that the family support group works effectively to
      help solve their problems.

PMID- 22413562
TI  - [Community care in home-visit nursing for drug-dependent people--questionnaire
      survey of home-visit nursing stations].
AB  - The present study aimed to clarify the present status of home-visit nursing for
      drug-dependent people and awareness among their caretakers. A questionnaire was
      sent to 279 stations that provide home-visit psychiatric nursing care. Among the
      89 stations that responded, 24 (26.9%) are currently providing home-visit nursing
      for drug-dependent patients, while 36 (40.4%) had experience doing so in the
      past. Although many stations recognized that drug-dependent patients need home
      visit nursing, their practices tended to be based on trial and error due to
      insufficient knowledge about the actual conditions and recovery processes of drug
      dependence. Compared to stations that had experience with home-visit nursing for
      drug-dependent patients, stations without such experience were more concerned
      about the safety of caretakers and their insufficient specialist knowledge about
      drug dependence.

PMID- 22413563
TI  - Depression and suicide risk of outpatients at specialized hospitals for substance
      use disorder: comparison with depressive disorder patients at general psychiatric
      clinics.
AB  - The present study used a self-reporting questionnaire to compare suicide risk in
      outpatients being treated for substance use disorder at specialized hospitals to
      suicide risk in outpatients being treated for depressive disorder at general
      psychiatric clinics. Although patients in both groups exhibited an equal severity
      of depression, the patients with drug use disorder had a higher suicide risk than
      those with depressive disorder. These findings indicate that drug-abusing
      patients at specialized hospitals may have a severe risk of committing suicide,
      suggesting that carefully assessing the comorbidity of depression with drug abuse
      may be required for preventing suicide in drug-abusing patients.

PMID- 22413564
TI  - [Relation between television commercial of alcoholic beverage and alcoholism].
AB  - BACKGROUND AND PURPOSE: Alcoholism is a disease that greatly ruins body mental
      health, family's health, and a social property. Moreover, it is a disease that a
      few drinking are connected with the danger of the relapse because there is a
      control trouble of the drinking desire. The purpose of this survey is to clarify
      the relation between television commercial of alcoholic beverage (CM) and
      alcoholism. METHODS: Questionnaire survey on CM and the drinking desire of
      alcoholism was carried out. Participants were 104 abstinent patients (AP) and 221
      healthy control subjects (HCS). HCS were ruled out alcohol dependence syndrome
      range by Alcohol Use Disorders Identification Test. Statistical analysis was
      performed using Chi-square and Fisher's exact tests as well as adjusted residuals
      to compare AP and HCS. In addition, AP was analyzed the relationship between
      period of abstinence and CM. RESULTS: The average period of abstenence from
      drinking was 3.38 +/- 1.55 years. AP had the experience of receiving stimulation
      to the drinking desire by CM. AP had the unpleasantness to the CM. Also, they
      hoped to discontinue CM, they felt the unpleasantness when they watched CM.
      Generally, three years are considered to be a stability period after abstains
      from drinking. Thirty-seven% of AP with 3 years and 27% of AP with 5 years
      answered "It is very which question about "I want to drink alcohol when I watched
      CM of alcohol beverage". CONCLUSIONS: It was suspected the CM stimulation was a
      risk element of an external trigger of the drinking desire, and AP had
      significantly felt "unpleasant" and hoped that "Discontinuance of CM". It was
      suggested that it is necessary to reconsider the CM stimulation from the
      viewpoint of relapse prevention of AP.

PMID- 22413565
TI  - [The relationship between glycogen synthase kinase-3 beta (GSK3B) -50T/C -1727A/T
      polymorphisms and alcoholism].
AB  - As a help of the mechanism elucidation of alcoholism, we studied the relationship
      between glycogen synthase kinase 3-beta (GSK3B) -50T/C and -1727A/T
      polymorphisms, which are reported to relate to bipolar disorder. We genotyped the
      two polymorphisms in GSK3B gene using a polymerase chain reaction (PCR) in 71
      health controls and 47 alcoholics. In this study, there was no significant
      difference in the frequency of GSK3B -50T/C and -1727A/T polymorphisms between
      alcoholics and controls. We suggested that there was no significant association
      of GSK3B -50T/C and -1727A/T polymorphisms with alcoholism.

PMID- 22413566
TI  - [Promising therapy of neural stem cell transplantation for FASD model--neural
      network reconstruction and behavior recovery].
AB  - OBJECTIVES: It has been elucidated that psychiatric disorders are associated with
      impairment of the brain neural network. Reduction in brain size and hypoplasia of
      the basal ganglia and corpus callosum have been reported in Fetal Alcohol
      Spectrum Disorder (FASD). It is believed that the formation of the neural network
      is influenced by alcohol exposure during the fetal period. Additionally, it is
      well known that the functional expression of CNS consequences of prenatal alcohol
      exposure includes cognitive and attentional processes, as well as social
      behavioral problems. It has also been reported that abnormal 5-HT neuron
      development can be reversed by treatment with a 5-HT1A agonist in a prenatal
      alcohol exposure model. However, these treatments are prophylactic. Without early
      intervention, the consequences of FASD are permanent. Recently, emerging evidence
      suggest that many clinical symptoms observed in psychiatric disease are likely
      related to neural network disruptions including neurogenesis dysfunction. Neural
      stem cell (NSC) transplantation has been investigated in areas such as brain
      injury, stroke and neurodegenerative diseases and may be a way to reverse
      neurogenesis dysfunction. In the present work, we evaluated the usefulness of
      intravenous transplantation of NSCs in the FASD model rat focusing on the
      possibility of regenerative therapy, particularly regarding behavioral
      abnormalities, for FASD rats. RESULTS: Abnormal behaviors FASD model rats suggest
      that reduced social activity , and cognitive dysfunction are major symptoms in
      FASD patients. Intravenous NSC transplantation appeared to partially correct
      these behavioral abnormalities in FASD model rats. In the Amygdala areas
      intravenous NSC transplantation appears to have partially regaenerates expression
      of PSD95 in FASD model rats. CONCLUSIONS: The results suggest that intravenous
      NSC transplantation may be an advanced approach to recover neural network damage
      and CNS dysfunction in FASD and possibly other psychiatric disorders.

PMID- 22413567
TI  - [Effects of smoking and caffeine on pharmacological treatment for patients with
      schizophrenia and depression].

PMID- 22413568
TI  - [Association of obesity and other cardiovascular risk factors with stroke the
      Japan Arteriosclerosis Longitudinal Study--Existing Cohorts Combined (JALS-ECC)].
AB  - OBJECTIVES: To assess the relationship between metabolic risk factors and the
      incidence of stroke stratified by obesity, by conducting a meta-analysis using
      individual participant data from prospective cohort studies. METHODS: A total of
      19,173 individuals from 10 cohort studies participated at baseline after 1985.
      Metabolic risk factors were defined using the established criteria in Japan.
      Participants were subdivided into five categories according to the levels of risk
      factors and obesity defined by BMI > or = 25 (kg/m2). Multivariate adjusted
      hazard ratios (HRs) for the incidence of stroke and the population attributable
      risk (PAR) were estimated by Poisson regression. RESULTS: During an average 7.1
      year follow-up period, 374 stroke events occurred. Hypertension was highest among
      the risk factors not concerned with BMI stratification. The HR for stroke was
      2.48 (95% CI: 1.75-3.5) for BMI < 25 with 1 other risk factor and 3.75 (2.58
      5.45) with 2 or more, 2.38 while it was (1.58-3.59) for BMI > or = 25 with 0 or 1
      factor and 3.26 (2.11-5.02) with 2 or more. The HR was significantly elevated in
      all categories with one or more risk factors. The PAR was highest in the category
      of BMI < 25 with 1 risk factor (23.3%) and second highest in the category of BMI
      < 25 with 2 or more. The respective PARs for BMI > or = 25 with 0 or 1 and 2 or
      more risk factors were 8.1% and 8.0%. Similar results were found from the
      analyses of different stroke subtypes. CONCLUSION: The HR was found to be
      significantly elevated with the number of risk factors both with and without
      obesity. The attributable risk for stroke was larger in the non-obese group.
      Therefore, public health intervention based only on obesity may miss many of
      those at high risk of stroke so the focus should not only be on obesity but also
      cardiovascular risk factors.

PMID- 22413569
TI  - [Blood pressure control through awareness of hypertension among female in-home
      caregivers].
AB  - OBJECTIVES: Our purpose was to clarify the situation regarding blood pressure
      control through awareness of hypertension among female groups of in-home
      caregivers and non-caregivers. METHODS: We used one existing data generated
      between December 2005 and April 2007. The subjects were females who were
      suffering from hypertension (66 caregivers were aged 49-84 years; 52 non
      caregivers were aged 47-81 years). We defined persons suffering from hypertension
      on the basis of results of a self-administered questionnaire and blood pressure
      values. On the question of awareness of hypertension, we defined the persons who
      replied positively to any one of "I have hypertension," "I have suffered from
      hypertension," or "I take antihypertensive agents" as belonging to the "awareness
      group." We categorized the other respondents, who replied to all three questions
      in the negative as belonging to the "non-awareness group." We used blood pressure
      values, to build an index of the control with the chi2 test and the t-test for
      statistical comparisons. Values of P < 0.05 were considered statistically
      significant. RESULTS: The results showed that blood pressure values of caregivers
      in both the awareness group and the non-awareness group were high (awareness
      group vs non-awareness group overall SBP: 148 +/- 20 mmHg vs 154 +/- 9 mmHg, DBP:
      79 +/- 13 mmHg vs 82 +/- 10 mmHg, P > 0.05). Furthermore, values were
      significantly lower for the awareness than non-awareness group with respect to
      the non-caregivers (SBP: 135 +/- 15 mmHg vs 149 +/- 7 mmHg, DBP: 73 +/- 10 mmHg
      vs 78 +/- 6 mmHg). Caregivers who took the antihypertensive agent in the
      awareness group demonstrated high values exceeding SBP 140 mmHg, which was the
      hypertensive standard value, not different from the values for caregivers not
      taking such medication. (taking vs non-taking SBP: 148 +/- 21 mmHg vs 149 +/- 8
      mmHg). CONCLUSION: Among the caregivers, it was not only the members of the non
      awareness group but also those of the awareness group who were found to have high
      blood pressure values. Though the caregivers took antihypertensive agents, their
      blood pressure values remained high.

PMID- 22413570
TI  - [Development of a scale to measure career orientation in public health nurses
      working in Japanese administrative agencies and relationships with demographic
      characteristics].
AB  - OBJECTIVES: The aim of this study was to develop a career-orientation scale for
      public health nurses (PHNs) working in local government agencies in Japan, and to
      examine the relationships of the scale with PHNs' demographic characteristics.
      METHODS: Self-administered questionnaires were mailed to 7,170 PHNs in 10
      prefectures. Items for the scale were determined by conducting a principal factor
      analysis using varimax rotation. Reliability was examined by calculating a
      cumulative contribution ratio and a Cronbach's alpha coefficient. A second survey
      was performed with participants who had given the relevant consent. RESULTS: For
      the first questionnaire, we received replies from 2,065 PHNs (28.8%), of whom
      2,003 (97.0%) provided valid responses. For the second questionnaire, we received
      valid responses from 222 out of the 252 participants. Five orientation factors
      were selected, managerial, engagement, service, professional, and stability,
      along with 19 items. The cumulative contribution ratio was 46.9% and the
      Cronbach's alpha reliability coefficient was 0.863. The average exact match ratio
      for the responses from the first and second questionnaires was 59.7% (each item;
      47.7-72.10%, each participant; 12.0-92.0%). Multiple regression analysis
      extracted the following four autonomous variables: experience of start-up of
      organization-making, presence of a role model, cooperative family, and years of
      experience as PHN (R2 = 0.052). CONCLUSION: The results indicate that the number
      of factors and items in our scale was appropriate for simple self-assessment.
      High values for factor loadings and reliability coefficients indicate a high
      intrinsic consistency. However, reproducibility requires further investigation,
      because the average exact match ratio of each participant greatly varied from
      individual to individual.

PMID- 22413571
TI  - [Study on dilemma and strategy of community support network by community
      organization for prevention of isolated death in an urban area].
AB  - OBJECTIVES: Isolated death of elderly is recognized as a severe social problem in
      public health and it is an urgent requirement that a supportive community network
      be organized so that its occurrence is minimized. The purpose of this research
      was to analyze actual issues of a supportive community network for elderly within
      the community and to obtain clues for useful actions to prevent isolated death of
      elderly individuals in the future. METHODS: The subjects were 14 representatives
      of a supportive community network for elderly in A City, B Ward and C District
      (as a junior high school segment). The research was conducted with a qualitative
      inductively approach using the Focus Group Interview (FGI). Interviews were
      focused on difficulties and perspectives within their daily support activities in
      the community, and were held three times during October 2009 to March 2010. The
      FGI records were then analyzed with meaningful minimal words and sentences,
      categorized codes, and then those codes were classified into subcategories or
      categories. RESULTS: Three categories, Individual, Neighborhood and Community
      network for elderly resulted from the analysis. Regarding difficulties, "Refusing
      supports or indifference", "Isolation or Tojikomori in the youth generation",
      "Lack of family support", "Relationships among their residents weakening
      gradually", "Unfamiliar newcomers and residents", "Residence feels burden on
      association with neighborhood", "Limitation of support activities under personal
      security", "Lack of resources for persons and places of gathering" were
      identified. On the other hand, perspectives in the community network for elderly
      were "Building relationships personally", "Invitation to community meetings as
      companions", "Development of safety confirmation", "Helping each other in the
      neighborhood", "Stimulate enforcement of bonding in daily life", "Making
      arrangements for regional administration and residents for supportive activites",
      "Fostering the trust and connection of residence". CONCLUSION: To further
      promotion and effective activities for community network for elderly by community
      residents, it is necessary that information be exchanged among resident
      organizations regarding their activities in achievement of social cooperation.

PMID- 22413572
TI  - [Recent advance in kidney and hypertension research].

PMID- 22413573
TI  - [Progress in blood purification medicine in 2011].

PMID- 22413574
TI  - [Recent progress in the management of CKD].

PMID- 22413575
TI  - [Acute kidney injury].

PMID- 22413576
TI  - [Fluid and electrolytes].

PMID- 22413577
TI  - [Topics on nephritis: update 2012].

PMID- 22413578
TI  - [Nephrotic syndrome].

PMID- 22413579
TI  - [Vitamin D-related progressive renal insufficiency in an elderly patient with
      postsurgical hypoparathyroidism associated with extensive brain calcification].
AB  - We present a 76-year-old female patient with dementia who has postsurgical
      hypoparathyroidism associated with extensive brain calcification and progressive
      renal insufficiency. She had been treated with vitamin D combined with calcium or
      vitamin D alone due to hypoparathyroidism for 8 years. However, intermittent
      hypercalcemia including hypercalcemic crisis (serum Ca 15.2 mg/dL) and
      progressive renal dysfunction had developed. This patient was transferred to our
      long-term care hospital because of worsening dementia. Since laboratory data at
      admission revealed hypercalcemia and azotemia, alfacalcidol (1 microg/day) was
      discontinued. However, severe hypocalcemia (3.9 mg/dL) occurred later, while her
      azotemia was improved. With a low dose of alfacalcidol(0.25 microg/day), the
      serum calcium level is now below normal (approximately 7.0 mg/dL). There is
      neither hypocalcemic symptom nor exacerbation of renal insufficiency. From the
      clinical history of recurrent hypercalcemic episodes and renal calculi observed
      on computed tomography, the progression of renal insufficiency was considered to
      be related to persistent hypercalciuria caused by vitamin D and calcium,
      especially vitamin D therapy.

PMID- 22413580
TI  - Dentistry: a profession at the crossroads.

PMID- 22413581
TI  - ADA looks toward future at annual session.

PMID- 22413582
TI  - Diagnostic discussion: Botryoid odontogenic cyst (BOC).

PMID- 22413583
TI  - Controlling your healthcare costs: low-cost group plans.

PMID- 22413584
TI  - Buying or leasing--the dental dilemma: why owning your own commercial space is
      not as profitable as you might think.

PMID- 22413585
TI  - Practice values in decline?

PMID- 22413586
TI  - A deer in the headlights.

PMID- 22413587
TI  - Our membership crisis and the value of metrics.

PMID- 22413588
TI  - Will the FTC kill ACOs and clinical integration?

PMID- 22413589
TI  - Using third-party financing to help today's patient pay for treatment and care.
AB  - Patients walking into your practice today are different than the ones you saw a
      few years ago. Larger deductibles and out-of-pocket costs may cause many of them
      to put off recommended treatment. What can you do to ease patients' cost concerns
      and help them move forward with the care they want and need? Creating a
      comprehensive financial policy that includes a third-party patient financing
      program is a good place to start. Here's how to ensure that you select the best
      program for you.

PMID- 22413590
TI  - From the operating room to the office: paradigm shift in the economics of
      surgical practice.
AB  - In the past decade, there has been a trend from doing procedures in the hospital
      operating room and the ambulatory treatment center to performing procedures in
      the doctor's office. This trend is becoming more prevalent as doctors have
      recognized that they have more control over their practices by working in the
      office rather than at a hospital or ambulatory treatment center. This article
      will focus on the trend and provide financial examples of this movement and why
      doctors need to be cognizant of their increased productivity in the office.

PMID- 22413591
TI  - Preparing your practice for any emergency scenario: your practice continuity
      plan.
AB  - A disaster resulting in a temporary cessation of your practice operations does
      not have to mean a permanent shut down of your practice if you are ready to meet
      possible interruption. With a plan in place and proper insurance coverage, a
      major or minor disaster can be met and overcome, and you can continue seeing your
      patients. It is important to review while an emergency--such as Hurricane Irene-
      is still fresh in your mind what happened and what needs to be done to strengthen
      your practice for the next time.

PMID- 22413592
TI  - Keys to securing data as a practitioner.
AB  - With patient identity theft on the rise, it's important that practitioners and
      patients alike know how to prevent a security breach. Because of HIPAA,
      physicians that are covered entities are required to take action to protect their
      patients' medical records or protected health information. Physicians and medical
      centers should be proactive while securing sensitive data. Some of these
      safeguards are physical security, electronic security, monitoring, and employee
      training.

PMID- 22413593
TI  - Decoding incident-to and provider-based billing: ensuring payment and avoiding
      liability.
AB  - In this increasingly complex world of Medicare reimbursement, physicians must
      constantly review their billing practices to ensure compliance with all Medicare
      requirements. "Incident-to" billing and provider-based billing are two areas that
      present unique challenges for providers, especially those practicing in hospital
      owned practices such as hospital outpatient departments. Both incident-to and
      provider-based billing limit providers' abilities to bill for and receive
      reimbursement in those practice settings. The Office of Inspector General's 2012
      Work Plan Report identified both incident-to billing and place-of-service errors
      as two of the many areas for investigation and compliance efforts in 2012. This
      article focuses on identifying the unique point-of-service challenges presented
      by physicians practicing in hospital outpatient departments or hospital-owned
      clinics.

PMID- 22413594
TI  - First impressions and beyond: marketing your practice in touch points--Part I.
AB  - Often medical administrators or providers call in a marketing expert when they
      feel the practice is lacking the growth they want. What's on their mind is
      usually how to bring in more patients, and they automatically look to external
      marketing strategies. However, one of the most important elements to successfully
      marketing a practice is making sure you haven't created a turnstile, where new
      patients are coming often but not returning or being converted into loyal,
      referring patients. When new patients are going as quickly as they are coming,
      you aren't building solid growth. Loyal, referring patients are powerful
      marketing assets-they are in the community speaking good of you and your practice
      from first-hand experience. You can create this atmosphere of loyal, referring
      patients by providing positive touch points that fulfill the needs of your
      patients. Touch points are the groundwork supporting other types of marketing.
      This article covers three important touch points that are crucial to a positive
      patient experience.

PMID- 22413595
TI  - How not to reinvent the wheel.

PMID- 22413596
TI  - Tips for medical practice success in the upcoming accountable care era.
AB  - Due to the unsustainable cost of healthcare, the movement to accountable care
      will be inevitable. This author predicts that recent Medicare Accountable Care
      Organization (ACO) regulations will energize ACO development. There are specific
      practical strategies every medical practice leader should know in order to
      navigate this new healthcare environment successfully. There is a window of
      opportunity, which will not stay open long, to control a medical practice's
      destiny in molding a fair, sustainable, and successful ACO. Not being prepared
      and defaulting to the status quo through passivity is also a choice that promises
      more work for less compensation for medical practices. The choice is clear, and
      the blueprint for success is available.

PMID- 22413597
TI  - The right patient.
AB  - This article offers professional opinions and advice on how physicians should
      prepare in order to protect themselves and their practices during this turbulent
      time in healthcare reform. This article presents real-life scenarios to help
      physicians understand what they may face and what actions they should take in
      anticipation of the future in healthcare. The article focuses on the concept of
      "the right patient," defining the characteristics of patients that benefit the
      financial aspect of a practice and those who do not. Its purpose is not to
      encourage physicians to deny care to patients who are poorly insured or
      uninsured, but to guide in the establishment of a smart and safe balance between
      the two. Strategies are discussed on how to attract the right patient and what
      these patients mean to the practice. The importance of practice marketing is also
      highlighted, along with an emphasis on the necessity of change in order to
      survive in the future healthcare environment.

PMID- 22413598
TI  - Working effectively with older patients: 25 do's and don'ts for medical practice
      employees.
AB  - Many if not most medical practice employees will be working with an increasingly
      larger number of older adults in the years to come. Yet medical practice
      employees who are younger may have trouble relating to their older patients and
      may unwittingly be making their communication with older patients more difficult.
      This article suggests 25 practical strategies for medical practice employees who
      work with older patients. It describes appropriate language for medical practice
      personnel to use and specific language to avoid when speaking of and to older
      patients. It teaches them to recognize signs of ageism both in themselves and in
      their older patients. It offers practical suggestions for accommodating the
      physical and cognitive needs of older adults. This article also suggests ways
      that medical practice employees can establish trust-based relationships with
      their older patients. It describes how they can navigate the challenges that can
      arise when family members and other caregivers become part of the medical
      equation. And it offers practical advice about scheduling, escorting, seating,
      communicating with, and remaining open-minded to the particular needs of older
      patients. Finally, this article explores behavioral challenges that can emerge
      when working with older adults, strategies for coping with family interference,
      and signs of elder abuse.

PMID- 22413599
TI  - Marketing your practice in a social world.
AB  - Social media use has moved beyond just being a way for family and friends to keep
      in touch. Now it is imperative that all businesses implement a social media
      strategy into their overall marketing plan. Medical practices are no exception.
      Using social media within your medical practice will allow you take your
      marketing to a new level of success. It also allows you to connect with patients
      on a more personal, less corporate level.

PMID- 22413600
TI  - Strategic planning to reduce medical errors: Part I--diagnosis.
AB  - Despite extensive dialogue and a continuing stream of proposed medical practice
      revisions, medical errors and adverse impacts persist. Connectivity of vital
      elements is often underestimated or not fully understood. This paper analyzes
      medical errors from a systems dynamics viewpoint (Part I). Our analysis suggests
      in Part II that the most fruitful strategies for dissolving medical errors
      include facilitating physician learning, educating patients about appropriate
      expectations surrounding treatment regimens, and creating "systematic" patient
      protections rather than depending on (nonexistent) perfect providers.

PMID- 22413601
TI  - A culture of safety: a business strategy for medical practices.
AB  - Physician practices can enhance their economics by taking patient safety to a new
      level within their practices. Patient safety has a lot to do with systems and
      processes that occur not only at the hospital but also within a physician's
      practice. Historically, patient safety measures have been hospital-focused and 
      driven, largely due to available resources; however, physician practices can
      impact patient safety, efficiently and effectively, with a methodical plan
      involving assessment, prioritization, and compliance. With the ever-increasing
      focus of reimbursement on quality and patient safety, physician practices that
      implement a true culture of safety now could see future economic benefits using
      this business strategy.

PMID- 22413602
TI  - Public speaking for the healthcare professional: part II--the program.
AB  - The first article of this series discussed the preparation for speakin at a
      dinner program. This article will discuss the actual program an what you can do
      to capture and hold the attention of your audience

PMID- 22413603
TI  - What's that, you say? Employee expectations of privacy when using employer
      provided technology--and how employers can defeat them.
AB  - Two 2010 court cases that determined the effectiveness of policies governing
      employees' use of employer-provided communication devices can be used to guide
      employers when constructing their own technology policies. In light of a policy
      that stated that "users should have no expectation of privacy or
      confidentiality," one case established that the employer was in the right.
      However, a separate case favored the employee due, in part, to an "unclear and
      ambiguous" policy. Ultimately, employers can restrict the use of employer
      furnished technology by employees by: 1) clearly outlining that employees do not
      have a reasonable expectation of privacy in their use of company devices; 2)
      stating that any use of personal e-mail accounts using employer-provided
      technology will be subject to the policy; 3) detailing all technology used to
      monitor employees; 4) identifying company devices covered; 5) not exposing the
      content of employee communications; and 6) having employees sign and acknowledge
      the policy.

PMID- 22413604
TI  - Be your own consultant: measure your revenue cycle.

PMID- 22413605
TI  - Viewing art immitates life.

PMID- 22413606
TI  - Dialysis access maintenance.

PMID- 22413607
TI  - ICD-10: stroke.

PMID- 22413608
TI  - Reducing errant ordered radiology exams.
AB  - With grant funds, Providence Saint Patrick Hospital set out to reduce the
      occurrences of errant ordered radiology exams from clinicians. The goal was to
      also provide a tool that would assist in reducing unwarranted dose from
      diagnostic imaging modalities. An interactive web based utility for CT protocols
      was developed, which included ACR Appropriateness Criteria that was easy to use
      and maintain. The second stage of the program will be expanded to include more
      modalities, as well as to provide patients with a convenient source of
      information.

PMID- 22413609
TI  - The leap from Doppler to ultrafast Doppler.
AB  - A new technological breakthrough is ongoing with the advent of massive parallel
      computing capabilities. This technology is the enabler to a new concept:
      ultrafast ultrasound imaging. UltraFast Doppler enables frame rate increases by a
      factor of 5 to 10 compared to conventional color Doppler, typically from 60 up to
      200Hz, without sacrificing field of view or spatial resolution. Complex flow
      dynamics and transient flow event can be visualized in a much more accurate
      manner. Potential clinical benefits of this emerging technology include increased
      measurement accuracy and increased efficiency in patient management. Stenosis
      grading in carotids or calculation of resistance indexes in renal arteries could
      tremendously benefit from this technology.

PMID- 22413610
TI  - Reasonable accommodations.

PMID- 22413611
TI  - The Medicare hospital value-based purchasing program and imaging's role.
AB  - Medicare and other payors are simultaneously seeking both a reduction in overall
      healthcare expenditures and an improvement in the quality of care for covered
      individuals. This movement recognizes the widespread belief that poor quality of
      care is expensive. Medicare will initially make payments to hospitals for
      inpatient acute care services based upon the hospitals' achievement of certain
      performance standards, notably including patient experience of care. Imaging
      professionals should keep their eyes and ears open and playan active role in the
      changes that are occurring within their hospitals and their healthcare
      communities more generally.

PMID- 22413612
TI  - Taking a breast center one step further: implementing breast tomosynthesis.

PMID- 22413613
TI  - A culture of extraordinary care: part 6.

PMID- 22413614
TI  - Partnering for survival.

PMID- 22413615
TI  - Time to build? Reform uncertainties drive financial scrutiny for new projects.

PMID- 22413616
TI  - It's the process: how lean strategies can streamline hospital design.

PMID- 22413617
TI  - Smooth start: ensuring emergency power system performance.

PMID- 22413618
TI  - On target: innovative resource-conserving and power-generating technologies find
      a home at more hospitals.

PMID- 22413619
TI  - Lessons learned after disaster strikes.

PMID- 22413620
TI  - Show your expertise to the C-suite.

PMID- 22413621
TI  - Air and water: hospitals should prepare now for ASHRAE's upcoming Legionella
      standard.

PMID- 22413622
TI  - Ready for change: how ES departments can navigate health care challenges.

PMID- 22413623
TI  - Advance directives: Society president encouraging completion of health care POAs.

PMID- 22413624
TI  - General practice in Northern Wisconsin. 1905.

PMID- 22413625
TI  - Education and work.

PMID- 22413626
TI  - Expanded community health center--academic medical center partnerships.

PMID- 22413627
TI  - Students enrolled in school-sponsored work programs: the effect of multiple jobs
      on workplace safety and school-based behaviors.
AB  - BACKGROUND: Throughout the United States, over 70% of public schools with 12th
      grade offer school-sponsored work (SSW) programs for credit; 60% offer job
      shadowing programs for students. Wisconsin offers a variety of work-based
      learning programs for students, including, but not limited to, job shadowing,
      internships, co-op education, and youth apprenticeship programs. No research has
      compared workplace injury and school-based behaviors in students enrolled in SSW
      programs who work only 1 job compared with those who work multiple jobs. METHODS:
      A total of 6810 students in the 5 public health regions in Wisconsin responded to
      an anonymous questionnaire that was administered in 2003. The questionnaire asked
      about employment, injury, characteristics of injury, and school-based behaviors
      and performance. RESULTS: A total of 3411 high school students aged 14 to 18
      reported they were employed during the school year. Among the working students,
      13.5% were enrolled in a SSW program. Of the SSW students, 44% worked multiple
      jobs. SSW students who worked multiple jobs were more likely to do hazardous job
      tasks, to work after 11 PM, to work over 40 hours per week, to have a near-miss
      incident, to have a coworker injured, and to be injured at work. CONCLUSIONS: SSW
      students who are working multiple jobs are violating labor laws that put their
      safety and their school performance at risk. The responsibilities of employers
      and schools have to be addressed to ensure that SSW students are abiding by labor
      laws when working multiple jobs.

PMID- 22413628
TI  - Effective clinical education: strategies for teaching medical students and
      residents in the office.
AB  - PROBLEM: Educating medical students and residents in the office presents the
      challenges of providing quality medical care, maintaining efficiency, and
      incorporating meaningful education for learners. Numerous teaching strategies to
      address these challenges have been described in the medical educational
      literature, but only a few teaching strategies have been evaluated for their
      impact on education and office practice. METHODS: Literature on the impact of
      office-based teaching strategies on educational outcomes and on office efficiency
      was selected from a Pub Med search, from review of references in retrieved
      articles, and from the author's personal files. RESULTS: Two teaching strategies,
      "one-minute preceptor" (OMP) and "SNAPPS," have been shown to improve educational
      processes and outcomes. Two additional strategies, "Aunt Minnie" pattern
      recognition and "activated demonstration," show promise but have not been fully
      evaluated. None of these strategies has been shown to improve office efficiency.
      CONCLUSIONS: OMP and SNAPPS are strategies that can be used in office precepting
      to improve educational processes and outcomes, while pattern recognition and
      activated demonstration show promise but need further assessment. Additional
      areas of research also are suggested.

PMID- 22413629
TI  - Escherichia coli pyomyositis in an immunocompromised host.
AB  - BACKGROUND: Pyomyositis due to Escherichia coli (E. coil) is rarely reported in
      immunocompromised patients with hematological malignancy. CASE REPORT: We present
      a case report of a 34-year-old man who developed E. coli pyomyositis as a
      complication of acute myelogenous leukemia (AML). Magnetic resonance imaging
      (MRI) of the right hip suggested myofascial infection of the gluteal muscles, and
      a needle muscle aspiration grew E. coli phylogenetic group B2. The patient
      responded to intravenous piperacillin/tazobactam followed by prolonged oral
      levofloxacin. CONCLUSION: Pyomyositis should be suspected in all
      immunocompromised patients complaining of muscle pain and may exhibit signs of
      localized muscle infection. Appropriate antibiotic therapy targeting
      fluoroquinolone-resistant E. coli should be considered for initial empiric
      therapy of pyomyositis in immunocompromised patients.

PMID- 22413630
TI  - Large cervicothoracic thymic cyst causing prominent airway deviation in a 3-day
      old neonate.
AB  - Cervicothoracic mass in the pediatric population is uncommon and has a broad
      differential diagnosis. Frequently, masses in the cervical region present with
      airway compromise, particularly in younger patients. We present a case of an
      extremely large cervicothoracic mass causing airway obstruction in a 3-day-old,
      otherwise healthy male infant. Following awake intubation for airway protection,
      a 4.5 cm x 2.5 cm x 1.5 cm thymic cyst was removed. This case illustrates the
      wide differential diagnosis of cervicothoracic masses and shows the difficulty of
      preoperative diagnosis, especially in the case of thymic cysts with extension
      into the cervical space.

PMID- 22413631
TI  - The ABCs of ACOs.

PMID- 22413632
TI  - Reflections for the next generation of physicians.

PMID- 22413633
TI  - The mysteries of the head and neck.

PMID- 22413634
TI  - We can do more than assume the worst.

PMID- 22413635
TI  - Home care can reduce readmissions.

PMID- 22413636
TI  - Thanks for the respect.

PMID- 22413637
TI  - Music to their ears?

PMID- 22413638
TI  - Magic for sinus sufferers?

PMID- 22413639
TI  - A new look at an old standby.

PMID- 22413640
TI  - Why they regrow.

PMID- 22413641
TI  - Novel approach.

PMID- 22413643
TI  - Medicare cut to cost Minnesota physicians $270 million.

PMID- 22413642
TI  - Toward a unified profession.

PMID- 22413644
TI  - A cancer gone viral.

PMID- 22413645
TI  - A consideration of the tonsil question. 1918.

PMID- 22413646
TI  - The first new otologic disorder in a century: superior canal dehiscence syndrome.
AB  - Superior canal dehiscence syndrome is a recently described vestibular and hearing
      condition caused by an absence of bone over the arc of the superior semicircular
      canal. Patients with the condition present with a variety of perplexing symptoms
      including conductive hearing loss, hyperacusis, vertigo, autophony, and eye
      movement in response to sound. This article presents the case of a patient with
      the condition, discusses how it is distinct from other vestibular and hearing
      disorders, and describes how patients with this disorder can be diagnosed and
      treated.

PMID- 22413647
TI  - Meniere's disease: new concepts, new treatments.
AB  - Our understanding of Meniere's disease is being revamped. For decades, the
      condition was thought to be caused by excessive fluid retention (hydrops) in the
      endolymphatic spaces of the inner ear, which led to tears or ruptures of the
      membranous structures that affect hearing and balance. More recently, research
      has shown that hydrops is not always associated with Meniere's and ought not to
      be considered the ultimate cause of its symptoms. New theories center on the fact
      that Meniere's disease may not have a single cause but may well be a common
      endpoint of a variety of anatomic or physiologic variables, including ischemic or
      even autoimmune injuries. This article describes the new thinking about Meniere's
      and explains why current treatment approaches, although they are based on
      outdated understanding, may still be valuable for alleviating symptoms in some
      patients.

PMID- 22413648
TI  - Robotic surgery for head and neck cancer.
AB  - During the last decade, robotic surgery has evolved from a novelty to the
      preferred surgical method for urologic, gynecologic, thoracic, cardiothoracic,
      and gastrointestinal procedures. The use of robotics in head and neck surgery
      grew out of the success of other transoral surgical modalities used to remove
      head and neck tumors. This article reviews the evolution of head and neck
      surgery, the current capabilities of surgical robots, and anticipated future
      applications of this technology.

PMID- 22413649
TI  - Hyperacusis and misophonia: the lesser-known siblings of tinnitus.
AB  - Hyperacusis (decreased sound tolerance) and misophonia (fear of sound) are two
      conditions about which little is known. Consequently, physicians often struggle
      when they encounter patients who are affected by them. This article attempts to
      educate the medical community about hyperacusis and misophonia, both of which can
      have devastating effects on the lives of patients, and ways to manage them.

PMID- 22413650
TI  - Obstructive sleep apnea: a review and update.
AB  - Obstructive sleep apnea (OSA) is a common problem that plays a role in a number
      of other chronic health concerns including hypertension, atrial fibrillation,
      diabetes, and gastroesophageal reflux disease to name a few. In this article, we
      discuss the relationship between OSA and these conditions as well as how OSA is
      diagnosed and treated.

PMID- 22413651
TI  - HOPE clinic: a place to care.
AB  - The University of Minnesota Medical School and College of Pharmacy in Duluth
      worked with a local drop-in center in 2008 to start a free clinic. The HOPE
      (Health of People Everywhere) Clinic is a student-run, faculty-organized effort
      that offers students an opportunity to develop their clinical skills and learn
      how to work in interprofessional teams while providing needed care to people who
      are underserved or uninsured. This article describes how this initiative came
      about and the impact it is having on medical students.

PMID- 22413652
TI  - Revalidation for educators: status box, status quo, and status maintenance.

PMID- 22413653
TI  - Revalidation: administrative burden or golden opportunity?

PMID- 22413654
TI  - Testing of revalidation proposals: key findings from the pathfinder pilots.

PMID- 22413655
TI  - Revalidation and recertification: the process in the United States of America.

PMID- 22413656
TI  - Quality in continuing medical education: playing hide and seek.

PMID- 22413657
TI  - Verification of 'learning credits' by GP appraisers.
AB  - BACKGROUND: The RCGP CPD Learning Credits system aims to enable GPs to
      demonstrate knowledge and skills relevant to their daily practice. Credits are
      self-assessed and will form part of the 'evidence' necessary for successful
      revalidation. At an appraisal, GP appraisers verify the credits in terms of the
      time spent on the CPD activity and its impact on the GP's practice. The purpose
      of this study was to examine the extent to which GPs (as appraisees) are able to
      self-assess their own learning and, as appraisers, verify credits in a
      standardised way. METHOD: All 17 GP appraisers in NHS Lanarkshire were invited to
      participate in a study, which triangulated three sources of evidence on credits:
      self-rating, peer-assessment and workshop discussion. The resultant data were
      analysed on an Excel spreadsheet. Outcomes included self-assessed credit value,
      peer-assessed mean score (range) and free text. RESULTS: Of the 17 appraisers, 15
      completed the paperwork and 13 attended the workshop. GPs' self-assessed learning
      credits were equivalent to peer-assessed score in 5/15 cases, but considered
      overestimates in 4/15 and underestimates in 6/15 cases. The most extreme variance
      was for an oncology module, where the variance ranged from 28% to 200% of the
      self-assessed score. CONCLUSIONS: GPs have a variable understanding of how to
      award themselves learning credits and of how to judge the credits of potential
      appraisees. Without adequate resources for appraisal training, validated
      instruments, calibration and reliability, verification of the learning credit
      system will be flawed by its subjective and arbitrary nature.

PMID- 22413658
TI  - The implications of enhancing appraisal to meet the requirements of revalidation,
      as perceived by appraisers: a qualitative study in Scotland.
AB  - This paper describes a qualitative study which explored the possible impact of
      enhanced appraisal and the requirements of revalidation upon GP appraisers in
      Scotland. So far there has been little research examining the impact 'enhanced'
      appraisal may have on the appraisee or appraiser population. Key objectives were
      to identify potential benefits and problems with the introduction of enhanced
      appraisal for the appraiser population and to explore what they perceive its
      impact will be on the GP workforce more generally. Three focus groups were held
      with a purposive sample of 17 highly experienced GP appraisers from across
      Scotland between February and April 2010. The results showed that this group of
      appraisers perceived that they would need to become more prescriptive about the
      standard of basic paperwork and evidence that is submitted by an appraisee. This
      created some anxieties about taking on a more judgemental role. They were
      concerned about a possible need to inform a high-achieving GP that their evidence
      was insufficient. Concerns were also raised about appraisees becoming less open
      and candid during appraisal once the links to revalidation are in place.
      Uncertainty was expressed about the relationship between the appraiser and
      responsible officer (RO) and how appraisers should decide which appraisees ought
      to be flagged up to the RO. The need for clear, standardised summary forms (known
      as GP Scot 4 in Scotland) to be passed to the RO was highlighted. Some of the
      appraisers were unsure about the value of new types of evidence which will be
      required--notably MSF and continuing professional development (CPD) credits.
      However, a few appraisers noted that some early adopters of CPD credits liked
      this way of recording their learning whilst MSF could be valuable and was seldom
      controversial. Potential benefits of 'enhanced appraisal' were highlighted-
      particularly increased engagement from some GPs who have hitherto been reluctant
      appraisees. The appraisers in this study wanted further training for their role,
      particularly training and calibration in delivering MSF feedback and in verifying
      CPD credits. They were frustrated by delays to revalidation and concerned that
      enhanced appraisal might be implemented without sufficient support (remediation
      and IT systems) being in place. However, they remained cautiously optimistic that
      some of the formative elements of appraisal can be maintained and were content to
      continue as appraisers provided they receive appropriate training and support and
      provided adequate remediation systems are in place for those GPs requiring help.

PMID- 22413659
TI  - What do GP educators perceive to be the opportunities and challenges of
      introducing revalidation?

PMID- 22413660
TI  - Benefits of appraisal as perceived by general practitioners.
AB  - Appraisal for general practitioners (GPs) has been in place since 2002. We
      conducted a review of current literature on what benefits GPs perceived appraisal
      to offer. GPs recognised that appraisal offers the chance to reflect on their
      personal development, and promotes educational activity. Furthermore, there is a
      strong perception that appraisal encourages changes in clinical practice and
      offers additional benefits such as mentorship and motivational support for the
      doctor. The conclusion we draw is that GPs, and the patients that they treat,
      should continue to benefit from outputs of medical appraisal after the
      introduction of medical revalidation.

PMID- 22413661
TI  - Evaluation of GP appraiser development centres using emotional intelligence: can
      positive learning outcomes be transferred to practice?
AB  - This paper describes a longitudinal evaluation of six pilot medical appraiser
      development centres (ADCs) with GPs held between February and September 2009 in
      the Kent, Surrey and Sussex Deanery. The ADCs were developed using traditional
      development centre methods and incorporated the concept of emotional intelligence
      (El). Initial evaluation results have shown positive short-term outcomes relating
      to appraiser skills and self-confidence as well as transfer of learning. This
      paper extends this earlier evaluation by looking at appraiser and appraisee
      feedback approximately one year after the ADCs using a validated framework for
      training evaluation. We discuss the long-term affective, cognitive and
      behavioural learning outcomes and the impact participation in the ADCs has on the
      broader healthcare system, including effects upon patient care and safety.
      Limitations of the current project and opportunities for future research are
      discussed.

PMID- 22413662
TI  - Strengthening medical appraisal: reactions to proposals for a new appraisal
      system to support revalidation.
AB  - This paper introduces the first stage of the NHS Revalidation Support Team's
      (RST) proposals to strengthen medical appraisal. It reports on four focus groups
      held at London Deanery in 2010, with the aim of gauging initial reactions from
      general practitioners (GPs). The four groups consisted of two groups of
      appraisers and two groups of appraisees. After presentation of the proposals to
      strengthen appraisal, participants were invited to make comparisons between
      existing appraisal, and the new proposals, Interestingly, the matter which
      attracted most discussion was a proposal to include an element of self-assessment
      by the appraisee prior to appraisal, and not, as might have been expected, the
      proposals for assessment of the appraisee's progress towards revalidation by the
      appraiser. Since these focus groups, the model of strengthened medical appraisal
      referred to in this paper has been the subject of testing in the pathfinder
      pilot, a large scale pilot involving 3000 doctors in various settings in England.
      The evaluation of the pathfinder pilot was published (July 2011). After further
      refinement of the appraisal process, including taking into account new GMC and
      Royal College publications and more testing and piloting, the final version of
      medical appraisal to support revalidation, known as the Medical Appraisal Guide
      (MAG) is due to be published in March 2012, in time to permit the expected
      commencement of revalidation in late 2012.

PMID- 22413663
TI  - Lessons for revalidation: a case report of an external review for quality
      assurance of deanery appraisal systems for general practitioners.

PMID- 22413664
TI  - 'Doctors in difficulty': how can we help them to achieve their potential?

PMID- 22413665
TI  - Teaching non-verbal communication skills.

PMID- 22413666
TI  - Concordance focused practice: review of a simulated patient based workshop.

PMID- 22413667
TI  - Appraisal information needs of newly qualified GPs.

PMID- 22413668
TI  - Teaching multiple trainees in general practice: 'learning in 3D'.

PMID- 22413669
TI  - Developing a '5 R's' approach to enhance the GP trainee experience in hospital.

PMID- 22413670
TI  - Postgraduate certificate for GP appraisers.

PMID- 22413671
TI  - The e-learning site.

PMID- 22413672
TI  - How was it for you? Competency based selection of general practice educators.

PMID- 22413673
TI  - Improving the spread of appraisals throughout the year: a pilot of two management
      strategies.

PMID- 22413674
TI  - Remaining positive in the face of adversity.

PMID- 22413675
TI  - National pay system under threat as employers push for changes.

PMID- 22413676
TI  - Lansley's bill changes fail to win over unions.

PMID- 22413677
TI  - Patient outcomes improve when staff feel free to raise concerns.

PMID- 22413678
TI  - NHS employers join our campaign to ensure excellent patient care.

PMID- 22413679
TI  - Accentuate the positive in a time of uncertainty and staff cutbacks.

PMID- 22413680
TI  - 'Nurses have a duty to be kind, friendly and polite'.
AB  - In a new four-part series, we examine the four strands of fundamental care that
      are being highlighted by the Care campaign and show how some hospitals are taking
      steps to ensure improvements. This week we look at communication. Good
      communication is central to quality care, yet nurses concede that it is not
      always effective with patients.

PMID- 22413681
TI  - Tackling a weighty issue.
AB  - An MP is calling for government action to tackle increasing levels of obesity
      among nurses. Overweight and obese nurses need support from employers to make
      healthy food choices at work and become credible health educators and role
      models.

PMID- 22413682
TI  - A triumphant debut.
AB  - Nurse Christie Watson won the prestigious Costa first novel award for her book
      Tiny Sunbirds Far Away last month. In it she tells the story of a 12-year-old
      girl in Nigeria who trains to be a traditional midwife. Here, Ms Watson explains
      that nursing and writing are complementary careers, as both require resilience,
      hard work and an understanding of humanity.

PMID- 22413683
TI  - Introducing first-year student placements in critical care.
AB  - Pre-registration nurse education requires students to spend 50% of their
      programme in clinical practice. The intensive care unit (ICU) is an area that
      could accommodate students, provided that staff receive adequate support and
      preparation. This article discusses how staff in one ICU were prepared to support
      first-year nursing students and relates mentors' experience of assisting students
      at this stage of training. The article aims to give readers an insight into the
      types of activities that students can be involved in and the potential benefits
      of placements in an ICU for students.

PMID- 22413684
TI  - Improving care for people with learning disabilities in hospital.
AB  - Evidence suggests that people with learning disabilities have greater healthcare
      needs than the general population and that these needs are often unmet. A
      literature search was conducted to identify factors influencing general hospital
      care for people with a learning disability. Electronic databases, general
      internet searches and references from the initial search were used to identify
      relevant studies published between January 1990 and December 2010. Fourteen
      studies were identified that matched the inclusion criteria. Recurrent themes
      included the effect of being in hospital on the individual with a learning
      disability, attitude and knowledge of staff, the hospital environment, role of
      carers and recommendations for improvement. A critical appraisal tool was used to
      assess the quality of the selected literature. Despite limitations, all the
      studies contributed to the evidence base. Although much has been written about
      general hospital care for people with a learning disability, credible research in
      this area is lacking. The areas of good practice identified from the available
      literature need to be evaluated and disseminated so that all people with a
      learning disability can receive the best possible health care.

PMID- 22413685
TI  - Promoting patient safety in continence care.
AB  - Continence care is a fundamental component of nursing. Good quality continence
      care supports patient dignity and improves quality of life significantly.
      However, as with all aspects of health care, patients face a number of risks
      during the delivery of continence care and, perhaps more importantly, are at risk
      of harm when care is not given to the required standard. This article focuses on
      essential elements of continence care and explores pertinent risks to patient
      safety, which may occur if care is not individualised or delivered appropriately.

PMID- 22413686
TI  - Treating psoriasis.

PMID- 22413687
TI  - From diploma to degree.

PMID- 22413688
TI  - Revitalising a valuable role.

PMID- 22413689
TI  - Made to measure.

PMID- 22413690
TI  - When it rains, it pours: Blood thinners complicate a nosebleed.

PMID- 22413691
TI  - If you aren't reading, you're rusting! Reading is a career antioxidant.

PMID- 22413692
TI  - Small talk: Discourse with an educated man.

PMID- 22413693
TI  - Concussion management: Head injuries come with great risk. What should providers
      know about them?

PMID- 22413694
TI  - Learning from history: How will you lead EMS into the future?

PMID- 22413695
TI  - How to develop tactical EMS protocols.

PMID- 22413696
TI  - High-tech training preps agency: simulation assists Northwest Fire/Rescue
      District with emergency response.

PMID- 22413698
TI  - Electronic records: 21st century EMS: who likes paperwork anyway?

PMID- 22413697
TI  - Improving the information flow: Can an interoperable network architecture solve
      EMS communication woes?

PMID- 22413699
TI  - Managing unstable musculoskeletal injuries:.
AB  - Musculoskeletal injuries are commonly treated by prehospital providers. The
      American College of Surgeons Committee on Trauma supports the early management of
      musculoskeletal injuries including analgesia, repositioning and splint
      application. Even when patients have multiple injuries, it is important to apply
      splints to reduce internal bleeding, pain and the potential for fatty embolisms.
      Strongly consider administering analgesia to any patient with a suspected
      musculoskeletal injury; the majority of these patients go on to receive analgesia
      in the hospital while their time in the ambulance is likely the most
      uncomfortable period of their care. When applying a splint, remember that
      effective splints are complete, compact and comfortable.

PMID- 22413700
TI  - Understand the trauma triad of death: know its components to help protect
      patients.

PMID- 22413701
TI  - Coach class: who wouldn't benefit from a little scrutiny and feedback?

PMID- 22413702
TI  - Advances in diagnosis and management of hypokalemic and hyperkalemic emergencies.
AB  - With up to 56% of individuals taking diuretics likely to develop hypokalemia, and
      comorbid disease and many other types of medications having the potential to
      induce hyperkalemia, potassium abnormalities are some of the most commonly seen
      electrolyte abnormalities in the emergency department (ED). Unless recognized and
      treated appropriately, they can also be some of the most deadly. Symptoms
      accompanying potassium abnormalities are often vague, involving multiple organ
      systems. This evidence-based review discusses the etiology, differential
      diagnosis, and diagnostic studies for detecting hypokalemia and hyperkalemia,
      including managing laboratory errors that lead to factitious potassium findings.
      Recognition and treatment of life-threatening dysrhythmias in hypokalemia and
      hyperkalemia are key to managing these potassium abnormalities. Electrocardiogram
      (ECG) findings, treatment algorithms, and controversies on treating potassium
      abnormalities in the ED are discussed, with recommendations on criteria for
      disposition.

PMID- 22413703
TI  - [Inclusion: not always does every child benefit equally well from the same
      program].

PMID- 22413704
TI  - [Nursing symposium in Stuttgart as farewell to Elfriede Zoller: with gratitude
      for passionate commitment].

PMID- 22413705
TI  - [Breastfeeding groups - a foray through the provision of leadership assisted
      group meetings for nursing families in Germany].

PMID- 22413706
TI  - [Summer, sun, beach and "family care" on Mallorca].

PMID- 22413707
TI  - [Nursing care in the familiar environment: 24-hour home based nursing care as
      benefit of public health insurance and/or benefit through nursing insurance?].

PMID- 22413708
TI  - [On the article, "Using family midwives in the early intervention system - their
      role and responsibilities" KKS November 20 2011, pages 459-63].

PMID- 22413709
TI  - [Maria Walter: a great fighter for health and pediatric nursing].

PMID- 22413710
TI  - [Children in poverty in a wealthy land].

PMID- 22413711
TI  - [Unrest in the operating room: a study finds a correlation with postoperative
      infection rate].

PMID- 22413712
TI  - [Conscious sedation on the pediatric intensive care unit and nursing
      particularities].

PMID- 22413713
TI  - ["Forest, words, poetry": writing and speaking workshop at the Bernhard-Rose
      School in Berlin].

PMID- 22413714
TI  - Patients want to know.

PMID- 22413715
TI  - Dabigatran and atrial fibrillation: the alternative to warfarin for selected
      patients.
AB  - For patients with atrial fibrillation and a high risk of thrombosis, the standard
      prophylaxis is warfarin, an anticoagulant, at a dose adjusted to the INR.
      Warfarin and aspirin are both reasonable choices for patients with a moderate
      risk of thrombosis. Dabigatran, an oral anticoagulant that inhibits thrombin, has
      been authorised for patients with atrial fibrillation and a moderate or high risk
      of thrombosis, without associated valvular abnormalities. Clinical evaluation of
      dabigatran is based on a randomised "non-inferiority" trial comparing two doses
      of dabigatran (110 mg and 150 mg) taken twice daily, and adjusted-dose warfarin,
      in 18 113 patients treated for an average of 21 months. Overall mortality was
      about 4% per year and did not differ between the 3 groups. There was a greater
      reduction in the annual incidence of stroke or systemic embolism with the higher
      dose of dabigatran (1.1%) than with warfarin (1.7%). This is not the case for the
      lower dose (1.5%). In patients with good INR control, the difference in favour of
      the higher dose of dabigatran was no longer statistically significant. All-cause
      treatment discontinuation rates were higher with dabigatran than with warfarin
      (21% versus 17%, p<0.001). The incidence of serious bleeding did not differ
      statistically between warfarin and the higher dose of dabigatran (3.57% versus
      3.32%), but was lower with the lower dose of dabigatran (2.87%). Compared with
      warfarin, dabigatran appears to be associated with about a 0.2% excess of
      myocardial infarction (0.73% versus 0.53%). Dyspepsia is also more frequent with
      dabigatran (6% versus 1.4%). Hepatic adverse effects appear to be mild but need
      to be monitored. The effects of dabigatran are potentiated by combination with P
      glycoprotein inhibitors and drugs that impair renal function. Combination with
      other antithrombotic agents should also be avoided. Treatment with dabigatran
      does not require monitoring of haemostasis, whereas vitamin K inhibitors
      necessitate close INR monitoring. In contrast, renal function must be monitored,
      as renal impairment increases the risk of bleeding. Unlike vitamin K antagonists,
      there is no antidote for dabigatran overdose. In practice, warfarin remains the
      standard drug for patients with atrial fibrillation and a moderate or high risk
      of thrombosis. Aspirin is an alternative for moderate-risk patients. When the
      risk is significant and the INR cannot be maintained within the target range
      despite close monitoring, dabigatran is the alternative to warfarin, provided the
      patient is closely monitored, especially for changes in renal function.

PMID- 22413716
TI  - Eribulin: Heavily pretreated breast cancer: uncertain advantages, excessive
      adverse effects.
AB  - There is no standard treatment for women with metastatic breast cancer in whom
      multiple lines of chemotherapy, including anthracycline- and taxane-based
      regimens, have failed. Eribulin is now authorised for this indication in the
      European Union. Like taxanes, eribulin inhibits microtubule function. Initial
      evaluation is mainly based on a randomised controlled, but unblinded, trial
      comparing eribulin with various standard regimens chosen by the investigators.
      The median overall survival time was 2.7 months longer with eribulin (13.2 versus
      10.5 months, a statistically significant difference), while the time to cancer
      progression did not differ. The adverse effect profile of eribulin in this trial
      was similar to that of taxanes; neutropenia and peripheral neuropathy were the
      most frequent adverse effects. Several other adverse effects, including asthenia,
      loss of appetite and pain, affect quality of survival. In practice, the benefits
      of eribulin are uncertain and are currently outweighed by adverse effects. It is
      better to avoid eribulin and to focus on symptomatic treatment.

PMID- 22413717
TI  - Ambulatory care in France: too many adverse events.
AB  - A French study of adverse events linked to ambulatory care (the Evisa study) was
      conducted in France in 2008, using the same methodology as a 2004 national study
      (Eneis 1). It included 2946 patients hospitalised in the Aquitaine region and was
      designed to determine the proportion of hospital admissions that were due to
      serious adverse events in ambulatory care, as well as the proportion that were
      preventable. The overall mortality rate was not studied. Overall, 2.5% of
      hospitalised patients were admitted for adverse events related to ambulatory
      care, while the rate was as high as 14% in geriatric and neurology wards. About
      75% of the patients were admitted following therapeutic interventions, 20% after
      diagnostic procedures, and 5% after preventive procedures. The adverse events
      were considered preventable in nearly half of the cases. Drugs were involved in
      about 80% of the preventable serious adverse events, especially vitamin K
      antagonists, neuroleptics and diuretics. Twenty-nine cases were analysed in
      depth.The mechanisms leading to preventable serious adverse events necessitating
      hospitalisation were similar to those identified in 2004: lack of communication
      between caregivers, failure to regularly reassess ongoing treatments or health
      status, and difficulties in obtaining access to care. In practice, identifying
      and intercepting medical errors should be a priority for all healthcare
      professionals.

PMID- 22413718
TI  - Mobility aid-related accidents in children.
AB  - During the period 1991-2008, more than 63 000 children were examined in US
      emergency rooms following an accident related to a mobility aid: 40% of the
      children were less than 10 years old; 60% of the accidents occurred at home; and
      4.4% of the children were hospitalised. Wheelchairs were the devices most often
      involved (67%), followed by crutches and walkers. Most accidents involving
      children under 10 years old were linked to a walker or wheelchair, and mainly
      resulted in head injuries. Most of the accidents in older children involved
      crutches and caused lower-limb sprains. In practice, the correct use of mobility
      aids should be explained to parents and children, and information given about the
      circumstances most likely to lead to accidents. Children using these devices
      should be supervised if necessary.

PMID- 22413719
TI  - Varenicline: aggression and homicidal ideation.
AB  - Varenicline, a drug used for smoking cessation, carries a risk of
      neuropsychological adverse effects, including depression and suicide. Analysis of
      a series of detailed reports of aggression and homicidal ideation attributed to
      varenicline showed that most patients had no psychiatric history. These symptoms
      were often preceded by sleep disorders. Suicide and suicidal ideation were
      associated with signs of aggression in nearly one-third of cases. Aggressive
      symptoms recurred in patients who restarted varenicline. In practice, it is
      better to avoid using varenicline for smoking cessation and to use nicotine
      replacement instead when drug therapy is considered necessary.

PMID- 22413720
TI  - Fixed-dose glucose-lowering drug combinations: preventable lactic acidosis.

PMID- 22413721
TI  - Thalidomide: deafness.

PMID- 22413722
TI  - Drospirenone: venous thrombosis (continued).

PMID- 22413723
TI  - Pregnancy and alcohol: occasional, light drinking may be safe.
AB  - Many pregnant women drink varying quantities of alcohol, although several
      guidelines recommend total abstinence. What is known of the dangers of alcohol
      for the outcome of pregnancy and for the unborn child? To answer this question,
      we conducted a review of the literature using the standard Prescrire methodology.
      Fetal alcohol syndrome, which combines facial dysmorphism, growth retardation and
      intellectual disability, occurs in about 5% of children who are regularly exposed
      to at least five standard units per day (about 50 g of alcohol per day). Four
      studies have explored the link between heavy maternal alcohol use over a short
      period and the risk of cognitive impairment in the child. The results were
      inconclusive, however, and the authors failed to take concomitant chronic alcohol
      consumption into account. A methodologically sound study showed an increase in
      neurological abnormalities (seizures and epilepsy) when the mother drank heavily
      during short periods between the 11th and 16th weeks of pregnancy. There is a
      risk of cognitive and behavioural problems in children whose mothers regularly
      drank more than 2 standard units per day. Studies involving a total of about 150
      000 pregnancies sought a link between low-level alcohol consumption and abnormal
      pregnancy outcomes. Very few showed a statistically significant link, and the
      results are undermined by the failure to take other risk factors into account.
      Weekly consumption of 5 standard units or more during pregnancy has been linked
      to an increased risk of cryptorchidism. Studies in a total of 57 000 pregnancies
      showed no effect of minimal alcohol consumption on the risk of malformations. A
      study of 1000 pregnancies showed a statistically significant risk of major
      malformations, but there were several apparent biases. A link between infant
      mortality and alcohol consumption during pregnancy was examined in large cohort
      studies. Consumption of at least 4 standard units per week increased the risk of
      early neonatal death. Smoking further increased the risk. Daily alcohol
      consumption should be avoided during pregnancy. A face-to-face interview remains
      the best way of detecting at-risk drinking during pregnancy. Specific
      questionnaires (T-ACE and Tweak) can also be helpful. Women often spontaneously
      cut down on their drinking in early pregnancy. A clinical trial showed that women
      with at-risk drinking were more likely to reduce their consumption if they were
      informed of the risks for their pregnancy and their unborn child on several
      occasions than if they were simply given an information leaflet. In practice,
      women must be informed of the risks of alcohol consumption during pregnancy, but
      this must be done tactfully. The risks of minimal alcohol consumption should not
      be overstated.

PMID- 22413724
TI  - Pregnancy: another opportunity to raise the issue of alcohol.
AB  - A good doctor-patient relationship allows the issue of alcohol consumption to be
      raised. Simple questionnaires can also help.

PMID- 22413725
TI  - Anti-alcohol medication and pregnancy: weighing the risks.
AB  - When there is a major risk of alcohol withdrawal symptoms in a pregnant woman, a
      7-day course of benzodiazepine therapy has a positive harm-benefit balance.
      Medications designed to help maintain abstinence are not sufficiently effective
      to warrant initiating treatment during pregnancy.

PMID- 22413726
TI  - Alcohol during pregnancy: inform women, without overdramatising or inducing
      feelings of guilt.

PMID- 22413727
TI  - Learning from errors: a workshop for personal and collective reflection.
AB  - During the 2010 Prescrire Encounters, more than 90 participants attended a
      Preventing the Preventable workshop on learning from errors in order to provide
      high quality care. The workshop followed a standard method for reflection on
      medical errors: identifying and analysing preventable situations that resulted in
      errors, after which ideas for improvements were sought. During the reflection
      breakout sessions, participants described errors, expressed incentives and
      disincentives to talk about errors, and identified key messages. Most of the
      participants found these sessions valuable. The examination of medical errors
      helps to remove some of the obstacles that stand in the way of delivering high
      quality care to all patients. Some healthcare professionals are prepared to
      reflect on errors and to take action to overcome their reluctance to discuss
      them.

PMID- 22413728
TI  - Pharmaceutical quality: big pharma also at fault.

PMID- 22413729
TI  - With Medicare revenues at stake, ED managers place new importance on elevating
      the patient experience.
AB  - With a portion of Medicare revenue soon to be on the line based on patient
      satisfaction, ED managers have a heightened focus on making sure patients not
      only receive first-rate care, but that they also come away from the experience
      with good things to say. Some hospitals have implemented "patient centric"
      training for all employees, including the clinical staff, and they're getting
      regular feedback from patients on things they could do better. Furthermore,
      patient throughput--always an important factor--has taken on added significance.
      Beginning this fall, Medicare will begin withholding 1% of payments to hospitals
      so that it can use these funds to provide incentives to institutions that score
      high on patient satisfaction. The percent of payments withheld will rise to 2% by
      2017. ED managers have implemented rounding through the waiting areas so that
      patients and family members are kept informed, and they're coming up with new
      ways to shorten patient-to-provider times. Experts say patient views of time
      spent in the ED also impact satisfaction scores from inpatient stays.
      Sophistication in the art of cue management is helping some EDs clear waiting
      rooms and maximize resources.

PMID- 22413730
TI  - Expert: take aim at long wait times by mastering the art of cue management.

PMID- 22413731
TI  - Planning a brand new ED? Study up on acoustics, air quality, and patient wish
      lists.
AB  - Hospitals planning to construct new EDs have a golden opportunity to integrate
      designs and materials that can please both patients and providers. Experts say
      attention to acoustics, privacy, and air quality can lower stress levels and
      boost satisfaction. Further, designs that prioritize efficient work flows get
      high marks from providers. Experts advise hospital leaders to get considerable
      input from patients before designing a new ED facility. Privacy, quiet, and a
      connection to nature are top priorities for patients. Use design to enhance
      patient flow.

PMID- 22413732
TI  - Researchers find huge savings opportunity in oral form of IV drugs.
AB  - Researchers find that hospitals could save millions of dollars by switching
      commonly prescribed intravenous (IV) medications to their oral equivalents in
      patients who are able to take medications orally. These findings come from an
      analysis of 2010 computer records from one department at Johns Hopkins Hospital
      in Baltimore, MD, but researchers suggest such savings are possible hospital-wide
      and could be utilized with many additional IV drugs. Most IV drugs are much more
      expensive than their oral equivalent forms. Researchers conclude that the
      hospital could have saved more than $1 million by switching some patients over to
      the oral equivalent forms of four commonly prescribed IV drugs, and these savings
      are just for one department in one year. Additional savings related to reduced IV
      related infections and the costs of administering and maintaining IVs are also
      likely, say researchers. Education and clinical decision support tools are needed
      to make providers aware of opportunities to utilize the oral forms of IV
      medications.

PMID- 22413733
TI  - Clinical pharmacists with EM training slash medication errors, help to optimize
      therapies in the ED.
AB  - Pharmacists who specialize in emergency medicine are taking a place at the
      bedside in a small but growing number of EDs. Studies show the approach can make
      a big dent in medication errors and can quickly guide physicians toward optimal
      therapies with respect to trauma patients and other complex cases. Experts say
      clinical pharmacists provide an extra safeguard that is commonly missed in the
      fast-paced ED setting. Experts estimate that 10% of EDs have established clinical
      pharmacy programs in the past 10 years. Pharmacists serve on trauma teams, review
      medication orders, assist with medication titration, and act as a communication
      bridge between the ED and the inpatient pharmacy. Recent studies suggest
      pharmacists capture significantly more medication errors than other personnel,
      and that they help to speed patients with ST-elevation myocardial infarctions
      from the ED to the cardiac catheterization laboratory. Nurse and physician buy-in
      are critical to the success of a clinical pharmacist program in the ED.

PMID- 22413734
TI  - New 'patent accelerated care environment' aims to facilitate work flow, free up
      ED for acute care needs.
AB  - Faced with rising acuity levels and surging demand, Virginia Mason Medical Center
      modified the Clinical Decision Unit concept used in many EDs, and developed a new
      Patient Accelerated Care Environment (PACE) to care for observation patients,
      process patients for discharge, and to prepare patients for admission.The
      approach is designed to utilize ED beds for initial processing of patients,
      allowing resuscitative care if needed, and treating and releasing the patients
      with quick care needs. Using the Virginia Mason Production System, a methodology
      that is modeled after Toyota production techniques, developers designed an
      optimal work flow pattern and then built infrastructure to facilitate that
      process. All patients who present to the ED for care are seen by the ED team
      through a "team greet" approach. Approximately 35% to 40% of patients who come to
      the ED for care are transferred to the PACE unit. Patients assigned to the PACE
      unit typically remain there for 4 to 48 hours, depending on their care needs.

PMID- 22413735
TI  - Boost efficiency, patient satisfaction with staff-driven improvements.
AB  - A hospital-wide improvement effort has enabled Robert Wood Johnson University
      Hospital in Hamilton, NJ, to reinstitute a guarantee that patients arriving at
      the ED for care will be evaluated within 15 minutes and receive a medical
      examination within 30 minutes. Administrators used a team approach to identify
      bottlenecks and implement solutions, and they divided the ED into four zones,
      with provider teams responsible for each zone. Since implementing the guarantee
      in August of 2011, the ED has reduced its left-prior-to-medical-screening-exam
      rate from 3% to 1.4%, in an ED department that sees 50,000 patients per year. The
      zoning system in the ED has improved patient throughput and fostered
      accountability within the care teams responsible for each zone, say
      administrators. Overall care provider satisfaction has risen from the 75th
      percentile in 2010 to the 80th percentile in 2011, according to Press Ganey
      surveys.

PMID- 22413736
TI  - The efficacy of minimal contact interventions for acute tinnitus: a randomised
      controlled study.
AB  - Acute tinnitus can lead to substantial distress and eventually result in long
      lasting impairment. The aim of this study was to compare the efficacy of a
      cognitive-behavioural intervention (delivered as Internet self-management,
      bibliotherapy or group training) to the information-only control condition.
      Applicants suffered from subjective tinnitus for up to six months, were between
      18 and 75 years old and received no other tinnitus-related psychological
      treatment. A total of 304 participants were randomly assigned to one of the four
      study arms. Tinnitus distress, depressive symptoms, psychosomatic discomfort and
      treatment satisfaction were assessed. At the post-assessment tinnitus distress
      was significantly lower in the Internet and the group training conditions
      compared to the control condition. Inter-group effect sizes were moderate to
      large. At follow-up, all active training conditions showed significantly reduced
      tinnitus distress compared to the control condition (intention-to-treat
      analysis). An additional completer analysis showed a significant reduction in
      tinnitus distress only for the group condition. All effect sizes were moderate.
      There were no differences regarding psychosomatic discomfort, but depressive
      symptoms were reduced in the group condition at the post-assessment (intention-to
      treat analysis). Treatment satisfaction was significantly higher in the training
      conditions. The dropout rate was 39%. The present study shows that distress can
      be reduced as early as the acute stadium and that minimal-contact interventions
      are a promising way to do this. In particular, the Internet and group conditions
      led to a large, immediate decrease in distress, and the participants were highly
      satisfied with the training.

PMID- 22413738
TI  - Prevalence of ketoacidosis at diagnosis of childhood onset Type 1 diabetes in
      Wales from 1991 to 2009 and effect of a publicity campaign.
AB  - AIMS: To determine the proportion of cases of childhood Type 1 diabetes that
      present with ketoacidosis and any temporal trend. To assess the impact of a
      publicity campaign promoting earlier diagnosis. METHODS: We used an all-Wales
      register of incident cases with data on 2046 children from 1991 to 2009. The
      proportion with ketoacidosis at diagnosis was compared with the Yorkshire
      Childhood Diabetes Register. On World Diabetes Day posters were sent to every
      pharmacy, school and general practitioner surgery across Wales and radio
      interviews given. A questionnaire survey was conducted in Gwent to assess
      penetrance of the campaign. RESULTS: Annually, in 1991-2009 the proportion
      presenting with ketoacidosis varied between 20% and 33% (mean 25%) with no change
      over time. Similar proportions occurred in Yorkshire. Ketoacidosis was more
      common before age 5 years (37% of cases) than at age 5-9 years (20%) or 10-14
      years (23%) (P < 0.001). From November 2006-2007 30% of cases presented with
      ketoacidosis and from November 2007-2008 25% cases presented with ketoacidosis.
      After the campaign (November 2008-2009) 26% presented with ketoacidosis (P =
      0.72). The information had reached a low proportion of families. General
      practitioners referred immediately cases that presented to them. CONCLUSIONS:
      Over 20 years in Wales there has been no change in the proportion of children
      with Type 1 diabetes initially presenting with ketoacidosis. This presentation
      occurs in a higher proportion of new cases aged under 5 years. Publicity to
      increase awareness did not reduce the proportion with ketoacidosis at diagnosis
      in Wales. We need to get the educational message through to parents to reduce
      ketoacidosis at presentation.

PMID- 22413739
TI  - Circular dichroism probed by two-photon fluorescence microscopy in enantiopure
      chiral polyfluorene thin films.
AB  - Two-photon fluorescence scanning confocal microscopy sensitive to circular
      dichroism with a diffraction-limited resolution well below 500 nm is
      demonstrated. With this method, the spatial variation of the circular dichroism
      of thermally annealed chiral polyfluorene thin films has been imaged. We observed
      circular dichroism associated with submicrometer-sized domains showing
      helicoidally twisted macromolecular organization. Domains with opposite
      chiroptical properties, corresponding to left- or right-handed molecular
      organization, coexist in the film. Our results are consistent with those obtained
      by one-photon imaging and illustrate the potential of two-photon imaging for use
      in studying helical macromolecular organization.

PMID- 22413740
TI  - 'Andrology'- the New Journal of the American Society of Andrology and the
      European Academy of Andrology.

PMID- 22413737
TI  - The incredible ULKs.
AB  - Macroautophagy (commonly abbreviated as autophagy) is an evolutionary conserved
      lysosome-directed vesicular trafficking pathway in eukaryotic cells that mediates
      the lysosomal degradation of intracellular components. The cytoplasmic cargo is
      initially enclosed by a specific double membrane vesicle, termed the
      autophagosome. By this means, autophagy either helps to remove damaged
      organelles, long-lived proteins and protein aggregates, or serves as a recycling
      mechanism for molecular building blocks. Autophagy was once invented by
      unicellular organisms to compensate the fluctuating external supply of nutrients.
      In higher eukaryotes, it is strongly enhanced under various stress conditions,
      such as nutrient and growth factor deprivation or DNA damage. The
      serine/threonine kinase Atg1 was the first identified autophagy-related gene
      (ATG) product in yeast. The corresponding nematode homolog UNC-51, however, has
      additional neuronal functions. Vertebrate genomes finally encode five closely
      related kinases, of which UNC-51-like kinase 1 (Ulk1) and Ulk2 are both involved
      in the regulation of autophagy and further neuron-specific vesicular trafficking
      processes. This review will mainly focus on the vertebrate Ulk1/2-Atg13-FIP200
      protein complex, its function in autophagy initiation, its evolutionary descent
      from the yeast Atg1-Atg13-Atg17 complex, as well as the additional non-autophagic
      functions of its components. Since the rapid nutrient- and stress-dependent
      cellular responses are mainly mediated by serine/threonine phosphorylation, it
      will summarize our current knowledge about the relevant upstream signaling
      pathways and the altering phosphorylation status within this complex during
      autophagy induction.

PMID- 22413741
TI  - First case of trans apical implantation of an aortic valve in a patient with
      dextrocardia.
AB  - We describe the clinical presentation and implantation procedure of the first
      transcatheter aortic valve implantation described in a patient with dextrocardia.

PMID- 22413742
TI  - A promoter-swap strategy between the AtALMT and AtMATE genes increased
      Arabidopsis aluminum resistance and improved carbon-use efficiency for aluminum
      resistance.
AB  - The primary mechanism of Arabidopsis aluminum (Al) resistance is based on root Al
      exclusion, resulting from Al-activated root exudation of the Al(3+) -chelating
      organic acids, malate and citrate. Root malate exudation is the major contributor
      to Arabidopsis Al resistance, and is conferred by expression of AtALMT1, which
      encodes the root malate transporter. Root citrate exudation plays a smaller but
      still significant role in Arabidopsis Al resistance, and is conferred by
      expression of AtMATE, which encodes the root citrate transporter. In this study,
      we demonstrate that levels of Al-activated root organic acid exudation are
      closely correlated with expression of the organic acid transporter genes AtALMT1
      and AtMATE. We also found that the AtALMT1 promoter confers a significantly
      higher level of gene expression than the AtMATE promoter. Analysis of AtALMT1 and
      AtMATE tissue- and cell-specific expression based on stable expression of
      promoter-reporter gene constructs showed that the two genes are expressed in
      complementary root regions: AtALMT1 is expressed in the root apices, while AtMATE
      is expressed in the mature portions of the roots. As citrate is a much more
      effective chelator of Al(3+) than malate, we used a promoter-swap strategy to
      test whether root tip-localized expression of the AtMATE coding region driven by
      the stronger AtALMT1 promoter (AtALMT1(P)::AtMATE) resulted in increased
      Arabidopsis Al resistance. Our results indicate that expression of
      AtALMT1(P)::AtMATE not only significantly increased Al resistance of the
      transgenic plants, but also enhanced carbon-use efficiency for Al resistance.

PMID- 22413743
TI  - Dried blood spot analysis by digital microfluidics coupled to nanoelectrospray
      ionization mass spectrometry.
AB  - Dried blood spot (DBS) samples on filter paper are surging in popularity as a
      sampling and storage vehicle for a wide range of clinical and pharmaceutical
      applications. For example, a DBS sample is collected from every baby born in the
      province of Ontario, Canada, for quantification of approximately one hundred
      analytes that are used to screen for 28 conditions, including succinylacetone
      (SA), a marker for hepatorenal tyrosinemia. Unfortunately, the conventional
      methods used to evaluate DBS samples for newborn screening and other applications
      are tedious and slow, with limited options for automated analysis. In response to
      this challenge, we have developed a method to couple digital microfluidics (DMF)
      to nanoelectrospray ionization mass spectrometry (nESI-MS) for SA quantification
      in DBS samples. The new system is formed by sandwiching a pulled glass capillary
      emitter between the two DMF substrates such that the capillary emitter is
      immobilized without external seals or gaskets. Moreover, we introduce a new
      feedback control system that enables high-fidelity droplet manipulation across
      DBS samples without manual intervention. The system was validated by application
      to on-chip extraction, derivatization, and analysis of SA and other analytes from
      DBS samples, with comparable performance to gold-standard methods. We propose
      that the new methods described here can potentially contribute to a new
      generation of analytical techniques for quantifying analytes in DBS samples for a
      wide range of applications.

PMID- 22413744
TI  - Electrochemical deposition of germanium sulfide from room-temperature ionic
      liquids and subsequent Ag doping in an aqueous solution.
AB  - A facile room-temperature electrochemical deposition process for germanium
      sulfide (GeS(x)) has been developed with the use of an ionic liquid as an
      electrolyte. The electrodeposition mechanism follows the induced codeposition of
      Ge and S precursors in ionic liquids generating GeS(x) films. The
      electrodeposited GeS(x) films were characterized by scanning electron microscopy
      energy dispersive X-ray spectroscopy (SEM-EDS) and Raman and X-ray photoelectron
      spectroscopy (XPS). An aqueous-based Ag doping method was used to dope
      electrochemically grown GeS(x) films with controlled doping compared to the
      conventional process, which can be used in next-generation solid-state memory
      devices.

PMID- 22413746
TI  - Pharyngeal hairy polyps: five new cases and review of the literature.
AB  - Pharyngeal hairy polyps are rare lesions that present as a pedunculated mass that
      may arise from the oropharyngeal or nasopharyngeal regions of the pharynx. The
      mass has the potential to partially or completely obstruct pathways towards the
      trachea and/or esophagus resulting in respiratory distress and/or feeding
      difficulties respectively. They have a predilection for female infants of 6:1
      with the vast majority of the cases occurring in the infantile period. We report
      5 cases of the hairy polyp in female infants, one of which showed unusual
      presentation since it was diagnosed at ten months of age.

PMID- 22413747
TI  - Management of opioid-induced constipation in cancer patients: focus on
      methylnaltrexone.
AB  - Opioids are one of the most widely used therapies for the palliative treatment of
      cancer pain; however, despite their proven analgesic efficacy, they are
      associated with several adverse effects. Associated with psychological distress
      and multiple concomitant clinical concerns, constipation is the most commonly
      occurring adverse effect of chronic opioid therapy in cancer patients. Whilst
      prophylaxis remains the first-line management option, methylnaltrexone is a
      recommended treatment option for opioid-related constipation if administration of
      laxatives is ineffective. Due to its inability to cross the blood-brain barrier,
      methylnaltrexone exerts a peripheral inhibition of opioid-related effects without
      influencing the opioid-induced central effects; as a result, the analgesic effect
      of opioids is unaffected. Moreover, multiple clinical trials, albeit not always
      conducted specifically in cancer patients, have demonstrated that up to 4 months'
      treatment with either intravenous or subcutaneous methylnaltrexone provides
      effective relief from opioid-related constipation and is well tolerated.
      Preliminary evidence indicates that the addition of methylnaltrexone to standard
      care for opioid-related constipation may also be advantageous from a
      pharmacoeconomic perspective. In addition, preliminary data suggest that
      methylnaltrexone could be associated with some further clinical benefits other
      than the treatment of opioid-related constipation, such as the improvement of
      gastric emptying, the relief of nausea/vomiting, and the reduction of the risk of
      regurgitation and pulmonary aspiration. This narrative review examines the most
      recent evidence and evaluates the current role of methylnaltrexone in the
      management of opioid-related constipation, and its potential efficacy in cancer
      patients. The pharmacokinetics, pharmacodynamics, efficacy and tolerability of
      methylnaltrexone are discussed.

PMID- 22413748
TI  - Relative bioavailability study of a novel prodrug of tenofovir, tenofovir
      dipivoxil fumarate, in healthy male fasted volunteers.
AB  - BACKGROUND AND OBJECTIVE: Tenofovir dipivoxil fumarate (9-[(R)-2-[[bis
      (pivaloyloxymethoxy) phosphinoyl] methoxy] propyl] adenine fumarate) is a novel
      ester prodrug of tenofovir. It has been developed as an anti-hepatitis B virus
      clinical candidate. The purpose of this study was to determine the
      pharmacokinetic parameters of tenofovir dipivoxil fumarate (test) and the
      commercially available tenofovir disoproxil fumarate (Viread(r), reference). In
      addition, the bioavailability of tenofovir dipivoxil fumarate was evaluated in
      healthy male fasted subjects after a single comparatively equivalent dose.
      METHODS: This single-dose, randomized, two-way, open-label, crossover study was
      conducted at Xijing Hospital, Xi'an, China. The study drug was administered under
      fasted conditions. Serial blood samples were obtained over 72 hours after oral
      administration of each treatment. Bioavailability of the drug was assessed in
      accordance with the State Food and Drug Administration bioequivalence criteria.
      RESULTS: Eighteen subjects were enrolled and completed the study, with all study
      treatments being generally well tolerated. The geometric mean ratios (90%
      confidence interval [CI]) for maximum plasma concentration (C(max)), area under
      the plasma concentration-time curve from time zero to the last quantifiable
      concentration (AUC(last)), and area under the plasma concentration-time curve
      from time zero extrapolated to infinity (AUC(infinity)) were 124.49% (90% CI
      115.85, 133.79), 122.85% (90% CI 115.55, 130.62), and 122.43% (90% CI 115.71,
      129.54), respectively. CONCLUSION: The relative bioavailability of tenofovir
      dipivoxil was 20% higher compared with tenofovir disoproxil fumarate; this result
      was consistent with the preclinical data.

PMID- 22413749
TI  - Proteases, proteolysis and inflammatory molecules in the tears of people with
      keratoconus.
AB  - PURPOSE: To investigate the expression of proteases, proteolytic activity and
      cytokines in the tear film of people with keratoconus. METHODS: Basal tears from
      people with keratoconus, from individuals who had undergone corneal collagen
      cross-linking for the treatment of keratoconus, and from normal controls were
      collected using a capillary tube. Corneal curvature of each subject was mapped.
      The total protein in tears was estimated. Levels and activity of proteases in the
      tears were analysed using specific antibody arrays and activity assays. RESULTS:
      The total tear protein level was significantly reduced in keratoconus (4.1 +/-
      0.9 mg/ml) compared with normals (6.7 +/- 1.4 mg/ml) (p < 0.0001) or subjects who
      had undergone corneal collagen cross-linking (5.7 +/- 2.3 mg/ml) (p < 0.005).
      Significantly (p < 0.05) increased tear expression of matrix metalloproteinases
      (MMP) -1, -3, -7, -13, interleukins (IL) -4, -5, -6, -8 and tumour necrosis
      factor (TNF) -alpha, -beta were evident in keratoconus. Tear IL-6 was the only
      cytokine significantly (p < 0.05) increased in tears of keratoconus subjects
      compared with the collagen cross-linked group. No significant difference in tear
      proteases were observed between the normal and the cross-linked groups, although
      the expression of TNF-alpha was significantly (p < 0.05) increased in the cross
      linked group compared with the controls. Elevated gelatinolytic (87.5 +/- 33.6
      versus 45.8 +/- 24.6 FIU, p < 0.0001) and collagenolytic (6.1 +/- 3.2 versus 3.6
      +/- 2.0 FIU, p < 0.05) activities were observed in tears from keratoconus
      compared with normal subjects. The activity of tear gelatinases (69.6 +/- 22.2
      FIU) and collagenases (5.7 +/- 3.3 FIU) in the collagen cross-linked group was
      not significantly different compared with either keratoconus or normals.
      CONCLUSION: Tears of people with keratoconus had 1.9 times higher levels of
      proteolytic activity and over expression of several MMPs and cytokines compared
      with tears from controls. Further investigations are required to study the
      possible implications of these changes and whether they can be used to monitor
      disease progression or determine the success of corneal collagen cross-linking.

PMID- 22413750
TI  - Perinatal outcome of monochorionic diamniotic twin pregnancies managed from early
      gestation at a single center.
AB  - AIM: The aim of this study was to evaluate the perinatal outcome of monochorionic
      diamniotic (MD) twin gestations managed from early gestation onward at a single
      center. MATERIAL AND METHODS: This was a retrospective single-cohort study,
      spanning 6 years, of 219 MD twin pregnancies who received prenatal care before 14
      weeks of gestation and delivered at our center. The subjects were all under the
      same perinatal management protocol. The incidence of fetal or neonatal death,
      major neurological complications at 28 days of age, twin-twin transfusion
      syndrome (TTTS), twin anemia-polycythemia sequence, and discordant birth was
      evaluated. Laser surgery was offered for TTTS at less than 26 weeks; however,
      selective feticide was not performed. RESULTS: Pregnancy termination was selected
      in two cases. Miscarriage occurred in two (1%) of the cases and preterm delivery
      occurred in 91 (42%). In regard to perinatal outcome at 28 days of age, 195 (89%)
      women possessed two live infants and 205 (94%) possessed at least one live
      infant. The overall survival rate was 92% (403/438). The prevalence of TTTS was
      17 cases (8%), seven of whom underwent laser surgery. Four cases of twin anemia
      polycythemia sequence were diagnosed postnatally (2%); discordant birth was
      diagnosed in 24 (12%). Major neonatal neurological abnormalities were noted in
      six cases (2%). CONCLUSIONS: The incidence of perinatal complications in 219 sets
      of MD twins managed from early gestational age to the neonatal period in one
      perinatal center was demonstrated. The incidence of TTTS was 8%; the survival
      rate was 89% at 28 days of age.

PMID- 22413751
TI  - A comparison of intracoronary with intravenous glycoprotein IIb/IIIa inhibitors
      during percutaneous coronary intervention in patients with acute coronary
      syndrome: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: It is still debatable whether intracoronary (IC) administration of
      glycoprotein IIb/IIIa inhibitors (GPIs) is superior to intravenous (IV)
      administration for patients with acute coronary syndrome (ACS) undergoing
      percutaneous coronary intervention (PCI). METHODS: We performed a meta-analysis
      of randomized controlled clinical trials. A literature search was conducted for
      relevant trials. Primary end-points were short-term (1-3 months) and mid-/long
      term (6/12 months) major adverse cardiovascular events (MACEs) (mortality,
      reinfarction, target vessel revascularization [TVR]). Secondary end-points were
      thrombolysis in myocardial infarction (TIMI) grade flow, TIMI myocardial
      perfusion grade (TMPG) flow, left ventricular ejection fraction (LVEF) within 2
      weeks, and bleeding complication. RESULTS: Twelve studies were included in the
      meta-analysis. IC administration of GPIs did not decrease short-term mortality
      (OR: 0.71, 95% CI: 0.41-1.23, P = 0.22) and reinfarction rate (OR: 0.76, 95% CI:
      0.45-1.29, P = 0.31) compared with IV administration. There was a trend toward
      reduction of short-term TVR rate in IC group compared with IV group but not
      reaching statistical significance (OR: 0.57, 95% CI: 0.31-1.04, P = 0.07). IC
      administration of GPIs significantly increased TIMI grade 3 flow (OR: 1.48, 95%
      CI: 1.06-2.06, P = 0.02) and TMPG grade 2-3 flow (OR: 2.63, 95% CI: 1.53-4.51, P
      = 0.0004) compared with IV administration. No significant difference was observed
      in long-term MACEs rate, LVEF, and bleeding complication between the 2 groups.
      CONCLUSION: IC administration of GPIs in patients with ACS undergoing PCI can
      significantly increase target coronary flow and myocardial reperfusion without
      increasing the risk of bleeding complication, but cannot improve clinical outcome
      compared with IV administration.

PMID- 22413752
TI  - Gross motor development in children adopted from orphanage settings.
AB  - AIM: This study sought to examine the effect of environmental enrichment on the
      motor skills of children adopted from orphanage settings. We investigated balance
      and bilateral coordination skills in 33 internationally adopted
      postinstitutionalized children (16 males, 17 females; age range 8 y 5 mo-15 y 10
      mo; mean age 10 y 9 mo; SD 2 y 2 mo) and compared them with 34 non
      institutionalized children (21 males, 13 females; age range 8 y 3 mo-14 y 10 mo;
      mean age 11 y 2 mo; SD 2 y 1 mo) being raised in their birth families. METHOD:
      The children were individually administered the balance and bilateral
      coordination subtests of the Bruininks-Oseretsky Test of Motor Proficiency in a
      research laboratory. Parents completed questionnaires about developmental
      history, family environment, and orphanage care. RESULTS: Postinstitutionalized
      children showed motor system delays compared with the non-institutionalized
      comparison children (postinstitutionalized balance mean 9.44, SD 5.92, comparison
      children balance mean 14.12, SD 4.39; postinstitutionalized bilateral
      coordination mean 11.97, SD 5.43, comparison children mean 19.97, SD 3.97). The
      length of time that children remained institutionalized before adoption predicted
      balance delays (b=-1.57, t=-2.33, p=0.027) and the severity of caregiving
      deprivation the children experienced correlated with bilateral coordination (r=
      0.44, p=0.013). INTERPRETATION: These findings suggest that institutionalized
      settings do not provide the early life experiences needed for the development of
      age-level motor skills later in childhood and that simple environmental
      enrichment following adoption is not enough to remediate skills. Children who
      have experienced early institutional care may benefit from early identification
      and targeted intervention.

PMID- 22413753
TI  - Use of a balloon catheter in management of the pelvic space following
      laparoscopic abdominoperineal excision.
AB  - AIM: Management of the pelvic space following laparoscopic abdominoperineal
      excision remains controversial. We describe a simple technique for obliteration
      of the pelvic space after laparoscopic abdominoperineal excision. METHOD:
      Pneumoperitoneum was re-established after completion of the operative procedure
      and a Foley catheter Ch. 24 was inserted through the right lower port under
      direct vision. The balloon of the catheter, placed in the presacral space, was
      filled with 50 ml of sterile saline and connected to passive drainage. The
      catheter was removed 10 days postoperatively. RESULTS: This technique was used in
      15 patients with the median age of 74 years (range 63-86). Eleven patients were
      treated with preoperative chemoradiotherapy. The median length of hospital stay
      was 9 days (range 5-11). Two patients (13.3%) treated with chemoradiotherapy
      developed a superficial perineal wound infection and four patients (26.6%) had a
      deep pelvic abscess, which required surgical drainage. The median time of
      perineal wound healing was 3 months (range 2-8). The median follow-up time was 36
      months (range 18-60). None of the patients developed perineal hernia or
      intestinal obstruction in the follow-up period. One patient underwent small bowel
      resection due to stenosis caused by radiation enteritis. There was no local
      recurrence, but two patients developed distant metastases after 12 months.
      CONCLUSION: Our results suggest that filling the pelvic cavity with a balloon
      catheter for 10 days results in the creation of a thin, fibrotic peritoneal layer
      which keeps the small intestine out of the pelvis and prevents loops of intestine
      adhering in the pelvic cavity.

PMID- 22413755
TI  - Atypical subacute cutaneous lupus erythematosus presenting as lichen planus
      pemphigoides with autoantibodies to C-terminus of BP180, desmoglein 1 and SS-A/Ro
      antigen.

PMID- 22413754
TI  - Functional analysis of the protein phosphatase activity of PTEN.
AB  - In vitro, the tumour suppressor PTEN (phosphatase and tensin homologue deleted on
      chromosome 10) displays intrinsic phosphatase activity towards both protein and
      lipid substrates. In vivo, the lipid phosphatase activity of PTEN, through which
      it dephosphorylates the 3 position in the inositol sugar of phosphatidylinositol
      derivatives, is important for its tumour suppressor function; however, the
      significance of its protein phosphatase activity remains unclear. Using two
      photon laser-scanning microscopy and biolistic gene delivery of GFP (green
      fluorescent protein)-tagged constructs into organotypic hippocampal slice
      cultures, we have developed an assay of PTEN function in living tissue. Using
      this bioassay, we have demonstrated that overexpression of wild-type PTEN led to
      a decrease in spine density in neurons. Furthermore, it was the protein
      phosphatase activity, but not the lipid phosphatase activity, of PTEN that was
      essential for this effect. The ability of PTEN to decrease neuronal spine density
      depended upon the phosphorylation status of serine and threonine residues in its
      C-terminal segment and the integrity of the C-terminal PDZ-binding motif. The
      present study reveals a new aspect of the function of this important tumour
      suppressor and suggest that, in addition to dephosphorylating the 3 position in
      phosphatidylinositol phospholipids, the critical protein substrate of PTEN may be
      PTEN itself.

PMID- 22413756
TI  - Procedural sedation combined with locoregional anesthesia for orthopedic surgery
      of the pelvic limb in 10 dogs: case series.
AB  - HISTORY: Ten dogs weighing 36 (21.4-75) kg [median (min-max)] and aged 3 (1-9)
      years scheduled for orthopedic surgery involving the stifle and structures distal
      to it. PHYSICAL EXAMINATION: Patients were classified as ASA I or II based on
      physical examination and basic hematology and biochemistry. MANAGEMENT: Each dog
      was managed using combined femoral and sciatic nerve blocks and procedural
      sedation with an intravenous infusion of propofol (0.07-0.15 mg kg(-1) minute(
      1)) and dexmedetomidine (1 MUg kg(-1) hour(-1)). None of the patients required
      conversion to general anesthesia as a result of response to surgical stimulation.
      The level of sedation was considered adequate in all patients and was
      characterized by occasional head lifting, thoracic limb stretching, yawning,
      lingual movements and swallowing. The eye position ranged from central to partial
      ventromedial rotation and was accompanied by spontaneous blinking. Intra
      operative cardiovascular and ventilatory variables were considered within
      acceptable limits. Muscle relaxation at the surgical field was adequate and
      surgical conditions were indistinguishable from those produced by general
      anesthesia. Intraoperatively, no additional analgesics were considered necessary.
      The quality of the recoveries was considered excellent in all cases. FOLLOW UP:
      No additional pain relief was required in any of the dogs within the 10 hours
      following blockade. All dogs ate 5.5 (3.5-12) hours after recovery. Ambulation
      occurred at 4 (2-6) hours. No evidence of esophagitis or aspiration pneumonitis
      has been reported during a period of 1 year after the procedures in any of the
      dogs. CONCLUSION: When combined with femoral and sciatic nerve blocks, procedural
      sedation has the potential of being an alternative to general anesthesia for
      orthopedic surgery involving the stifle and structures distal to it in the dog.

PMID- 22413757
TI  - Orbitofrontal cortex biases attention to emotional events.
AB  - We examined the role of orbitofrontal (OF) cortex in regulating emotion-attention
      interaction and the balance between involuntary and voluntary attention
      allocation. We studied patients with OF lesion applying reaction time (RT) and
      event-related potential (ERP) measures in a lateralized visual discrimination
      task with novel task-irrelevant affective pictures (unpleasant, pleasant, or
      neutral) preceding a neutral target. This allowed for comparing the effects of
      automatic attention allocation to emotional versus neutral stimuli on subsequent
      voluntary attention allocation to target stimuli. N2-P3a and N2-P3b ERP
      components served as measures of involuntary and voluntary attention allocation
      correspondingly. Enhanced N2-P3a amplitudes to emotional distractors and reduced
      N2-P3b amplitudes to targets preceded by emotional distractors were observed in
      healthy subjects, suggesting automatic emotional orienting interfered with
      subsequent voluntary orienting. OF patients showed an opposite pattern with
      tendency towards reduced N2-P3a responses to emotional distractors, suggesting
      impaired automatic orienting to emotional stimuli due to orbitofrontal damage.
      Enhanced N2-P3b responses to targets preceded by any affective distractor were
      observed in OF patients, suggesting bias towards voluntary target-related
      attention allocation due to orbitofrontal lesion. Behavioral evidence indicated
      that left visual field (LVF) attention performance was modulated by emotional
      stimuli. Specifically, OF patients responded faster to LVF targets subsequent to
      pleasant emotional distractors. We suggest that damage to the orbitofrontal
      circuitry leads to dysbalance between voluntary and involuntary attention
      allocation in the context of affective distractors with predisposition to
      posterior target-related processing over frontal novelty and affect-related
      processing. Furthermore, we suggest that orbitofrontal influence on emotion
      attention interaction is valence and hemisphere dependent.

PMID- 22413758
TI  - Psychiatric clinical course strengthens the student-patient relationships of
      baccalaureate nursing students.
AB  - Psychiatric nursing teaches students how to engage and communicate with patients
      who have severe emotional distress. Nurses need this knowledge as the majority of
      patients encountered in hospitals are distressed. This study explores the impact
      of a psychiatric clinical course in helping students learn to relate to
      distressed patients. The study used a mixed research methodology to survey 67
      baccalaureate students about their experiences in the placement portion of the
      psychiatric nursing course. The pre-clinical questions focused on students'
      anticipation regarding individuals with mental illness and how the clinical
      experience would affect them as nurses and as individuals. The post-clinical
      questions asked how the clinical experience affected them. The students stated
      that their time with patients had changed them. Ninety-nine per cent were no
      longer frightened of the patients. Students realized the patients were distressed
      and were glad to help them. This work sensitized them to the individual rather
      than the generic patient. It initiated a process in self-awareness, in
      sensitivity to the feelings of another person and in communication skills. These
      are steps in the development of an empathetic presence. The students recognized
      the need for these skills in all nursing. The authors recommend strategies to
      assist students in developing an empathetic presence.

PMID- 22413759
TI  - Risk factors for cardiovascular and cerebrovascular diseases among ethnic Germans
      from the former Soviet Union: results of a nested case-control study.
AB  - BACKGROUND: Diseases of the circulatory system (CVD) are the most common causes
      of death in developed countries. However, the prevalence of CVD varies between
      countries; for example, the mortality rate in Russia is about four times higher
      than in Western Europe. In a recent retrospective cohort study it was
      unexpectedly found that CVD mortality is lower among "Aussiedler" (ethnic Germans
      from the former Soviet Union) compared to the German population. METHODS: This is
      a case-control study, nested into a recent cohort study of migrants from the
      former Soviet Union. Relatives of cases and controls themselves were interviewed
      by telephone using a standardized questionnaire. To estimate relative risks via
      the odds ratio (OR), a conditional logistic regression procedure was performed.
      RESULTS: Commonly known risk factors for CVD were identified as relevant to
      Aussiedler. The best multivariate model for CVD includes five risk factors:
      consumption of alcohol, smoking, diabetes, cholesterol and consumption of sweets.
      For alcohol consumption and smoking, OR = 3.68 (95% CI, 1.58-8.58) and OR = 3.07
      (95% CI, 1.42-6.62), respectively. For diabetes mellitus and high cholesterol
      values, OR = 3.29 (95% CI, 1.50-7.39) and OR = 2.32 (95% CI, 1.11-4.88),
      respectively. The almost complete abdication of sweets is associated with a
      protective effect, OR = 0.34 (95% CI, 0.18-0.64). The prevalence of risk factors
      is somewhat different to that of the autochthon German population and partly
      explains the differences in CVD mortality between both groups. CONCLUSIONS: The
      reported lower prevalences of known risk factors of CVD such as alcohol
      consumption, high cholesterol, diabetes and smoking (in women) could contribute
      to a lower risk of CVD.

PMID- 22413760
TI  - CD133 immunomagnetic separation: effectiveness of the method for CD133(+)
      isolation from umbilical cord blood.
AB  - BACKGROUND AIMS: Umbilical cord blood (UCB) is a rich source of stem cells, the
      characterization and isolation of which requires specific stem cell markers and
      reliable and reproducible protocols. METHODS: We assessed CD133 isolation in 39
      UCB samples, using a commercial immunomagnetic cell-sorting protocol, and,
      because of its non-reproducibility, we applied optimized protocols in an effort
      to improve it. These included extra-labeling of the selected CD133(+)
      subpopulation and indirect labeling using anti-phycoerythrin (PE) microbeads,
      goat anti-mouse IgG microbeads or a combination of both. The CD34 isolation was
      used as a control. RESULTS: The mononuclear cell fraction expressed 0.53+/-0.06%
      CD133. The corresponding value for CD34 was 1.64+/-0.15%. Following the
      manufacturer's instructions, the CD34 isolation resulted in a population
      expressing 93+/-1.25% CD34 while, after the corresponding process, CD133(+)
      expression ranged from 10% to 85% (median 60%). The optimized isolation protocols
      did not result in improved CD133(+) yield. The variation in the purity of the
      CD133 population cannot be attributed to the different clones of CD133 used,
      because they do not cross-block, while other factors such as glycosylation, which
      could possibly interfere, do not apply in normal hematopoietic stem cells (HSC).
      CONCLUSIONS: CD34 isolation by the immunomagnetic method results in highly pure
      CD34(+) population, while the efficient and reproducible yield of a pure CD133(+)
      population is not feasible. Therefore quantification of the positive cells should
      follow each isolation procedure in order to confirm the number of CD133(+) cells.

PMID- 22413761
TI  - The cost effectiveness of human papillomavirus vaccines: a systematic review.
AB  - INTRODUCTION: Human papillomavirus (HPV) is one of the world's most common
      sexually transmitted infections, and has been associated with a number of
      cervical and non-cervical diseases, including cancer. HPV vaccines have been
      licensed for use in females for some time, but the quadrivalent vaccine has only
      recently become licensed for use in males. Many countries have adopted a
      vaccination programme for adolescent females based on results of cost
      effectiveness analyses. However, given the new indications for use of the vaccine
      in males, decision makers require information on the cost effectiveness of
      vaccinating males in order to make policy decisions on whether or not to fund
      such programmes. OBJECTIVE: Our objective was to conduct a qualitative systematic
      review to update a previously conducted review of HPV vaccine studies. METHODS:
      Articles were obtained from an extensive literature search to determine the cost
      effectiveness of implementing an HPV vaccination programme with routine cervical
      cancer screening. A total of 29 studies were included in this review. Seventeen
      of the included articles looked only at cervical disease outcomes, and 12 studies
      also included non-cervical disease outcomes. Four studies explored the economic
      impact of vaccinating both boys and girls. One study focused on a population of
      men who have sex with men (MSM). RESULTS: While different model structures, input
      parameters and baseline assumptions were used, the consistent message in studies
      that focused on female-only vaccination programmes was that routine vaccination
      of females is cost effective compared with cervical cancer screening alone.
      DISCUSSION: Based on the currently available literature, it appears that the
      addition of boys to a vaccination programme generally exceeds traditional cost
      effectiveness thresholds. The MSM population represents a potential additional
      target for routine HPV vaccination; however, more cost-effectiveness studies are
      required before making such a policy change.

PMID- 22413763
TI  - Mercury chloride increases hepatic alanine aminotransferase and glucose 6
      phosphatase activities in newborn rats in vivo.
AB  - This work investigated the in vivo and in vitro effects of HgCl2 and ZnCl2 on
      metabolic enzymes from tissues of young rats to verify whether the physiological
      and biochemical alterations induced by mercury and prevented by zinc are related
      to hepatic and renal glucose metabolism. Wistar rats received (subcutaneous)
      saline or ZnCl2 (27 mg/kg/day) from 3 to 7 days old and saline or HgCl2 (5.0
      mg/kg/day) from 8 to 12 days old. Mercury exposure increased the hepatic alanine
      aminotransferase (~6-fold) and glucose 6-phosphatase (75%) activity; zinc pre
      exposure prevented totally and partially these mercury alterations respectively.
      In vitro, HgCl2 inhibited the serum (22%, 10 MUM) and liver (54%, 100 MUM)
      alanine aminotransferase, serum (53%) and liver (64%) lactate dehydrogenase (10
      MUM), and liver (53%) and kidney (41%) glucose 6-phosphatase (100 MUM) from 10-
      to 13-day-old rats. The results show that mercury induces distinct alterations in
      these enzymes when tested in vivo or in vitro as well as when different sources
      were used. The increase of both hepatic alanine aminotransferase and glucose 6
      phosphatase activity suggests that the mercury-exposed rats have increased
      gluconeogenic activity in the liver. Zinc prevents the in vivo effects on
      metabolic changes induced by mercury.

PMID- 22413762
TI  - Antifungal chemoprophylaxis in children and adolescents with haematological
      malignancies and following allogeneic haematopoietic stem cell transplantation:
      review of the literature and options for clinical practice.
AB  - Invasive opportunistic fungal infections are important causes of morbidity and
      mortality in children and adolescents with cancer or haematopoietic stem cell
      transplantation (HSCT). Difficulties in establishing the diagnosis continue to
      delay antifungal therapy, and this has been shown to adversely impact on
      survival. Apart from ongoing attempts to improve early recognition, effective
      chemoprophylaxis of invasive fungal infections remains a goal of high priority in
      populations with disease-related incidence rates of 10% or higher. These include
      patients with acute myeloid leukaemia, high-risk acute lymphoblastic leukaemias,
      recurrent leukaemias and those following allogeneic HSCT. Incidence rates in
      other paediatric cancer entities, including autologous HSCT, are considerably
      lower and do not justify the general implementation of antifungal prophylaxis.
      The difficulties in obtaining a timely diagnosis, the consequences of infectious
      morbidity on delaying anticancer treatment, and mortality rates >20% and >50% for
      invasive yeast and mould infections, respectively, provide a clear rationale for
      antifungal prophylaxis in high-risk populations. However, while antifungal
      prophylaxis has become part of infectious disease supportive care algorithms in
      most paediatric leukaemia and allogeneic transplantation programmes, antifungal
      prophylaxis remains a topic of controversy, with no clear consensus amongst
      different centres and groups. This is largely based on the limited paediatric
      data, with only a small number of meaningful studies, and on the fact that the
      scientific evidence for the benefit of antifungal prophylaxis has been generated
      exclusively by prospective, randomized, clinical phase III trials conducted in
      adults with comparable, but not similar conditions. In this article, we briefly
      review the epidemiology of invasive fungal infections in children and adolescents
      with cancer and following HSCT; delineate regulatory principles of paediatric
      drug development with relevant examples for their successful implementation with
      new antifungal compounds; provide information on the pharmacology and paediatric
      development of current antifungal compounds; discuss for each compound the
      evidence for effectiveness as primary or secondary antifungal prophylaxis in
      adults and the pertinent data published in paediatric patients; and conclude by
      providing practical options for prophylaxis in children and adolescents with
      haematological malignancies and following allogeneic HSCT.

PMID- 22413764
TI  - Variants of the lamin A/C (LMNA) gene in non-valvular atrial fibrillation
      patients: a possible pathogenic role of the Thr528Met mutation.
AB  - BACKGROUND AND OBJECTIVE: Lamin A/C (LMNA) gene mutations cause dilated
      cardiomyopathy, often accompanied by conduction disturbances. Our aim was to
      search for LMNA mutations in individuals with atrial fibrillation. METHODS: A
      cohort of Polish subjects (N = 103) with non-valvular atrial fibrillation with a
      high (48.5%) prevalence of conduction system disturbances was screened for LMNA
      variants by direct DNA sequencing. RESULTS: We found a single non-synonymous
      variant (Thr528Met) in a 72-year-old patient with normal left ventricular
      function and episodes of advanced atrioventricular block. One of his two mutation
      carrying daughters had episodes of type I second-degree atrioventricular block on
      a 24-hour Holter ECG and peak exercise arrhythmia. Interpretation of cardiac
      anomalies observed in the other daughter was complicated by thyroid
      insufficiency. A Thr528Met weak pathogenic effect was supported by transient
      transfections of C2C12 mouse myoblasts and computationally. Another interesting
      variant was Ile26Ile (c.78C>T), found in a New York Heart Association class III
      patient with a depressed left ventricular ejection fraction (30%), left bundle
      branch block, and a family history of heart disease. Ile26Ile was absent in 246
      healthy individuals and was computationally predicted to interfere with splicing.
      CONCLUSION: LMNA mutations are not a frequent cause of atrial fibrillation even
      when conduction disease is present. Unlike the majority of LMNA mutations clearly
      associated with a severe clinical phenotype and a poor prognosis, Thr528Met
      results in a more subtle pathogenic effect, while Ile26Ile should be considered
      as a variant of unknown significance.

PMID- 22413765
TI  - Peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala: lack of
      association with weight gain in psychiatric inpatients treated with olanzapine or
      clozapine.
AB  - BACKGROUND AND OBJECTIVE: Weight gain is a common problem of treatment with
      atypical antipsychotics. However, the dimension of body weight change differs
      interindividually, and various genetic factors are considered to be associated
      with this effect. Peroxisome proliferator-activated receptor gamma (PPARG)
      Pro12Ala polymorphism and its reported relationship to type 2 diabetes
      susceptibility and body mass accumulation prompted us to investigate the impact
      of this single nucleotide polymorphism (SNP) on antipsychotic-induced changes of
      body weight and body mass index (BMI) in a naturalistic study design. METHODS:
      Included were 138 olanzapine- and 32 clozapine-treated psychiatric inpatients
      whose demographic data, medical anamnesis, and drug treatment were assessed at
      admission to hospital and 4 weeks thereafter. The PPARG Pro12Ala SNP was
      determined with a validated real-time PCR assay. RESULTS: In contrast to previous
      investigations, we did not detect significant variations of weight gain among the
      different PPARG Pro12Ala genotypes. CONCLUSION: Our results suggest that the
      examined polymorphism appears to play a minor or no role in clinical practice
      concerning antipsychotic drug-induced weight gain.

PMID- 22413766
TI  - High levels of the extracellular matrix proteoglycan decorin are associated with
      inhibition of testicular function.
AB  - Decorin (DCN), a component of the extracellular matrix of the peritubular wall
      and the interstitial areas of the human testis, can interact with growth factor
      (GF) signalling, thereby blocking downstream actions of GFs. In the present study
      the expression and regulation of DCN using both human testes and two experimental
      animal models, namely the rhesus monkey and mouse, were examined. DCN protein was
      present in peritubular and interstitial areas of adult human and monkey testes,
      while it was almost undetectable in adult wild type mice. Interestingly, the
      levels and sites of testicular DCN expression in the monkeys were inversely
      correlated with testicular maturation markers. A strong DCN expression associated
      with the abundant connective tissue of the interstitial areas in the postnatal
      through pre-pubertal phases was observed. In adult and old monkeys the DCN
      pattern was similar to the one in normal human testes, presenting strong
      expression at the peritubular region. In the testes of both infertile men and in
      a mouse model of inflammation associated infertility (aromatase-overexpressing
      transgenic mice), the fibrotic changes and increased numbers of tumour necrosis
      factor (TNF)-alpha-producing immune cells were shown to be associated with
      increased production of DCN. Furthermore, studies with human testicular
      peritubular cells isolated from fibrotic testis indicated that TNF-alpha
      significantly increased DCN production. The data, thus, show that an increased
      DCN level is associated with impaired testicular function, supporting our
      hypothesis that DCN interferes with paracrine signalling of the testis in health
      and disease.

PMID- 22413767
TI  - High Ki-67 expression in diffuse large B-cell lymphoma patients with non-germinal
      center subtype indicates limited survival benefit from R-CHOP therapy.
AB  - OBJECTIVES: Rituximab has significantly improved the survival of patients with
      DLBCL, especially those with non-germinal center B-cell-like (non-GCB) subtype.
      The impact of Ki-67 expression, an index of proliferation, on the clinical
      outcomes of patients with DLBCL has largely been unexplored. This study aimed to
      investigate whether Ki-67 expression is an indicator of outcome in DLBCL patients
      (especially non-GCB DLBCL patients) treated with standard chemotherapy combined
      with rituximab. METHODS: Expression of Ki-67 protein was examined
      immunohistochemically in 118 tumor specimens from patients newly diagnosed with
      DLBCL and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin,
      vincristine, and prednisone). RESULTS: Overall survival (OS) and progression-free
      survival (PFS) were lower in patients with high Ki-67 expression than in those
      with low Ki-67 expression (3-year OS: 65.2% vs. 81.7%, P = 0.030; 3-year PFS:
      56.4% vs. 73.3%, P = 0.020), similar in patients with GCB subtype and those with
      the non-GCB subtype (OS: P = 0.330; PFS: P = 0.287). According to Ki-67
      expression status by immunophenotype subgroups, patients with high Ki-67
      expression in non-GCB subgroup had the most unfavorable PFS and OS, comparing
      with the other three subgroups (P = 0.004 and P = 0.002, respectively). In
      multivariate analysis, non-GCB with high Ki-67 expression was an independent
      prognostic predictor of inferior survival in DLBCL patients treated with R-CHOP.
      CONCLUSION: For DLBCL patients with non-GCB DLBCL and high Ki-67 expression, the
      survival benefit from R-CHOP therapy is limited.

PMID- 22413768
TI  - Application of random amplified polymorphic DNA (RAPD) to detect genotoxic effect
      of trifluralin on maize (Zea mays).
AB  - Trifluralin is a widely used dinitroaniline herbicide throughout the world.
      However, limited efforts have been made to study its genotoxic effects on
      different plants. The present study aimed to evaluate the herbicide's genotoxic
      potential on maize (Zea mays) by using the random amplified polymorphic DNA
      (RAPD) technique. For this purpose, maize seedlings were treated with aqueous
      solutions of trifluralin at concentrations ranging from 0.5 to 3 ppm for 7 days.
      In the RAPD analyses, 15 primers were used and 91 bands were obtained, with an
      average of 6.06 bands per primer in the control seedlings. After trifluralin
      treatment, significant changes were observed in RAPD profiles. These changes
      included loss of normal bands and appearance of new bands, in comparison to the
      control group, and they were dose dependent. In addition, root growth and total
      soluble protein level in trifluralin-treated seedlings were analyzed and compared
      for genomic template stability (GTS), which was performed for the qualitative
      measurement of changes in randomly amplified polymorphic DNA (RAPD) profiles. The
      results showed that GTS, root growth, and total soluble protein content of the
      seedlings gradually decreased with an increase in trifluralin concentration.
      These findings suggest that the RAPD technique is a useful biomarker assay to
      evaluate the genotoxic effects of herbicides on plants.

PMID- 22413769
TI  - Active head lifting from supine in early infancy: an indicator for non-optimal
      cognitive outcome in late infancy.
AB  - AIM: To explore whether active head lifting from supine (AHLS) in early infancy
      is associated with cognitive outcome in the second year of life. METHOD: The
      presence of AHLS was always recorded in the notes of infants admitted to our
      tertiary neonatal intensive care unit. Random sampling was used to pair infants
      with AHLS with two comparison infants without AHLS whose sex, gestational age,
      birth year (1993-2009), time of assessment, and developmental test (Griffiths
      Mental Development Scales, Mental Scale of the Bayley Scales of Infant
      Development-II, or cognitive subtest of the Bayley Scales of Infant and Toddler
      Development-III) were comparable. Brain injury identified from neonatal cranial
      ultrasound scans was classified as no - mild or moderate - severe. Z-scores of
      cognitive test outcomes were calculated for multivariable analysis. RESULTS:
      Eighty-seven preterm (34 males, 53 females) and 40 term (17 males, 23 females)
      infants with AHLS were identified. AHLS was documented at a mean (corrected) age
      of 7.0 (SD 1.7) and 8.1 (SD 2.2) months respectively. The cognitive assessments
      were performed at a mean corrected age of 15.7 (SD 1.7) and 23.9 (SD 1.6) months
      in preterm infants, and 19.1 (SD 2.3) months in term infants. The mean cognitive
      outcome of preterm and term infants with AHLS was lower than that of infants
      without AHLS (p=0.002 and p=0.004 respectively). This remained after excluding
      infants with cerebral palsy with matching comparison infants (p=0.001 in preterm
      and p=0.001 in term infants). The mean difference was highest (1.35SD) between
      term male infants and comparison infants (p=0.001). INTERPRETATION: AHLS is
      associated with a less favourable cognitive outcome in the second year of life in
      preterm as well as in term-born infants than in comparison infants.

PMID- 22413770
TI  - The influence of a continuous rate infusion of dexmedetomidine on the nociceptive
      withdrawal reflex and temporal summation during isoflurane anaesthesia in dogs.
AB  - OBJECTIVE: To examine the influence of a low dose dexmedetomidine infusion on the
      nociceptive withdrawal reflex and temporal summation in dogs during isoflurane
      anaesthesia. STUDY DESIGN: Prospective experimental blinded cross-over study.
      ANIMALS: Eight healthy mixed breed dogs, body weight Mean +/- SD 26.5 +/- 8.4 kg
      and age 25 +/- 16 months. METHODS: Anaesthesia was induced with propofol and
      maintained with isoflurane (Fe'ISO 1.3%) delivered in oxygen and air. After
      stabilization, baseline recordings (time 0) were obtained, then a dexmedetomidine
      bolus (1 MUg kg(-1) IV) followed by a continuous rate infusion (1 MUg kg(-1)
      hour(-1)) or saline placebo were administered. At times 10, 30 and 60 minutes
      after the initial bolus, electrical stimulations of increasing intensity were
      applied over the lateral plantar digital nerve, and administered both as single
      and as repeated stimuli. The resulting reflex responses were recorded using
      electromyography. Data were analysed using a multivariable linear regression
      model and a Kruskal Wallis test for single stimulation data, and repeated
      measures anova and paired t-test for repeated stimulation data. RESULTS: The AUC
      for the stimulus-response curves after single stimulation were similar for both
      treatments at time 0. At times 10, 30 and 60 the AUCs for the stimulus-response
      curves were significantly lower with dexmedetomidine treatment than with placebo.
      Temporal summation was evident in both treatments at times 0, 10, 30 and 60
      starting from a stimulation intensity of 10 mA. The magnitude of temporal
      summation was smaller in dexmedetomidine than in placebo treated dogs at time 10,
      30 and 60, but not at time 0. CONCLUSIONS: During isoflurane anaesthesia, low
      dose dexmedetomidine suppresses the nociceptive reflex responses after single and
      repeated electrical stimulation. CLINICAL RELEVANCE: This experimental study
      confirms previous reports on its peri-operative efficacy under clinical
      conditions, and further indicates that dexmedetomidine might reduce the risk of
      post-operative chronic pain development.

PMID- 22413772
TI  - A welcome to Drosophila olfaction.

PMID- 22413771
TI  - The photoprotective protein PsbS exerts control over CO(2)  assimilation rate in
      fluctuating light in rice.
AB  - A direct impact of chloroplastic protective energy dissipation (qE) on
      photosynthetic CO(2) assimilation has not been shown directly in plants in the
      absence of photoinhibition. To test this empirically we transformed rice to
      possess higher (overexpressors, OE) and lower (RNA interference, RNAi) levels of
      expression of the regulatory psbS gene and analysed CO(2) assimilation in
      transformants in a fluctuating measurement light regime. Western blots showed a
      several-fold difference in levels of PsbS protein between RNAi and OE plants with
      the wild type (WT) being intermediate. At a growth light intensity of 600 MUmol
      m(-2) sec(-1) , the carboxylation capacity, electron transport capacity and dark
      adapted F(v)/F(m) (ratio of variable to maximum fluorescence) were inhibited in
      RNAi plants compared with WT and OE. The PsbS content had a significant impact on
      qE (measured here as non-photochemical quenching, NPQ) but the strongest effect
      was observed transiently, immediately following the application of light. This
      capacity for qE was several-fold lower in RNAi plants and significantly higher in
      OE plants during the first 10 min of illumination. At steady state the
      differences were reduced: notably at 500 MUmol m(-2) sec(-1) all plants had the
      same NPQ values regardless of PsbS content. During a series of light-dark
      transitions the induction of CO(2) assimilation was inhibited in OE plants,
      reducing integrated photosynthesis during the light period. We conclude that the
      accumulation of PsbS and the resultant qE exerts control over photosynthesis in
      fluctuating light, showing that optimization of photoprotective processes is
      necessary for maximum photosynthetic productivity even in the absence of
      photoinhibitory stress.

PMID- 22413773
TI  - Romantic relationships: do socially anxious individuals benefit?
AB  - Psychological health and interpersonal functioning mutually influence each other.
      Social anxiety has a pervasive effect on interpersonal functioning, resulting in
      smaller social networks, increased likelihood of being single or divorced, and
      less intimacy in relationships. However, little is known about how relationships
      affect socially anxious individuals in return. We utilized a structured interview
      to assess how romantic relationships were perceived as influencing three aspects
      of psychological health (well-being, social anxiety and comfort in social
      situations) and whether these patterns differed as a function of social anxiety
      in an undergraduate sample. The perceived importance of several reasons for these
      effects, including those that could be characterized as both protective and
      harmful, was also assessed. Relationships were perceived as having contributed
      positively in each domain. However, when positive and negative reasons were
      examined separately, socially anxious individuals reported benefiting more from
      the positive reasons and being harmed more by negative reasons. Further, social
      anxiety was associated with endorsing certain reasons as important.

PMID- 22413774
TI  - Dangling conversations: reflections on the process of creating digital stories
      during a workshop with people with early-stage dementia.
AB  - Care and compassion are key features of the NHS Constitution. Recent reports have
      identified a lack of compassion in the care and treatment of older people. Nurses
      draw on aesthetic knowledge, developed through engagement with the experience of
      others, when providing compassionate care. Patient Voices reflective digital
      stories are used in healthcare education to facilitate student engagement with
      the patient experience. Digital stories were made with seven people with early
      stage dementia as part of a learning package for student nurses. In this paper
      the authors reflect on their experience and observations from facilitating the 4
      day digital story-making workshop. Social theories of dementia provide a
      theoretical framework for understanding these reflections. Despite considerable
      challenges in developing a story, and anxiety about using the technology, reading
      and speaking, all participants engaged in creating their own digital stories.
      Positive changes in the participants' interactions were observed. These
      improvements appeared to be the product of the person-centred facilitation and
      the creative process which supported self-expression and a sense of identity.
      Nurses working in this way could facilitate ability of the person with dementia
      to participate in their care, and improve their sense of well-being by supporting
      self-expression.

PMID- 22413775
TI  - Cutaneous Mycobacterium marinum infection mimicking felon in a patient with
      psoriatic arthritis treated with infliximab.

PMID- 22413776
TI  - Impaired fasting glucose in combination with silent myocardial ischaemia is
      associated with poor prognosis in healthy individuals.
AB  - AIM: As both impaired fasting glucose and silent myocardial ischaemia are risk
      factors for cardiovascular disease and death, we hypothesized that these risk
      factors in combination would identify those subjects at the highest risk of
      adverse events. METHODS: Healthy individuals without diabetes (n=596, 55-75
      years) were examined for silent myocardial infarction (>= 1 mm ST-interval during
      >= 1 min) by ambulant 48-h continuous electrocardiogram monitoring and impaired
      fasting glucose (fasting plasma glucose 5.6-6.9 mmol/l). RESULTS: After 6.3
      years, 77 subjects met the endpoint of myocardial infarction and/or death. The
      prevalence of silent myocardial ischaemia at inclusion was 12.3% in subjects with
      impaired fasting glucose and 11.7% in subjects with normal fasting glucose,
      P=0.69. Subjects with impaired fasting glucose/silent myocardial ischaemia more
      often met the endpoint (36%) than subjects with impaired fasting glucose/no
      silent myocardial ischaemia (15%), subjects with normal fasting glucose/silent
      myocardial ischaemia (12%), and subjects with normal fasting glucose/no silent
      myocardial ischaemia (10%), respectively, (P<0.001). In a Cox model including
      these four study groups of interest, gender, age, smoking habits, blood pressure
      and total cholesterol, only subjects with impaired fasting glucose/silent
      myocardial ischaemia exhibited an increased risk of death or myocardial
      infarction (hazard ratio 2.5, P=0.016). CONCLUSION: The combination of impaired
      fasting glucose and silent myocardial ischaemia was associated with the poorest
      prognosis in middle-aged and older subjects without previously known glucose
      metabolic aberration and heart disease.

PMID- 22413777
TI  - Spectroscopic and crystallographic characterization of "alternative resting" and
      "resting oxidized" enzyme forms of bilirubin oxidase: implications for activity
      and electrochemical behavior of multicopper oxidases.
AB  - While there is broad agreement on the catalytic mechanism of multicopper oxidases
      (MCOs), the geometric and electronic structures of the resting trinuclear Cu
      cluster have been variable, and their relevance to catalysis has been debated.
      Here, we present a spectroscopic characterization, complemented by
      crystallographic data, of two resting forms occurring in the same enzyme and
      define their interconversion. The resting oxidized form shows similar features to
      the resting form in Rhus vernicifera and Trametes versicolor laccase,
      characterized by "normal" type 2 Cu electron paramagnetic resonance (EPR)
      features, 330 nm absorption shoulder, and a short type 3 (T3) Cu-Cu distance,
      while the alternative resting form shows unusually small A(||) and high g(||) EPR
      features, lack of 330 nm absorption intensity, and a long T3 Cu-Cu distance.
      These different forms are evaluated with respect to activation for catalysis, and
      it is shown that the alternative resting form can only be activated by low
      potential reduction, in contrast to the resting oxidized form which is activated
      via type 1 Cu at high potential. This difference in activity is correlated to
      differences in redox states of the two forms and highlights the requirement for
      efficient sequential reduction of resting MCOs for their involvement in
      catalysis.

PMID- 22413779
TI  - Improved chopping of a lithium beam for plasma edge diagnostic at ASDEX Upgrade.
AB  - The lithium beam diagnostic at ASDEX Upgrade routinely delivers electron density
      profiles in the plasma edge by lithium beam impact excitation spectroscopy. An
      accurate background subtraction requires a periodically chopped lithium beam. A
      new, improved chopping system was developed and installed. It involves a voltage
      modulation for the extractor electrode and the beam deflection plates. The
      modulation of the extractor electrode reduces the unused portion of lithium ions
      and improves the stability of the beam with respect to its position. Furthermore,
      the data indicate an extended emitter lifetime. The extractor chopping was also
      found to be insensitive to sparks. The deflection chopping experiments
      demonstrated beam chopping in the kilohertz range. The significantly higher
      modulation frequency of the deflection chopping improves background subtraction
      of fast transient events. It allows a more accurate density measurements in the
      scrape off layer during impurity injections and edge localized modes.

PMID- 22413778
TI  - From "best practice" to "next practice": the effectiveness of school-based health
      promotion in improving healthy eating and physical activity and preventing
      childhood obesity.
AB  - BACKGROUND: In 2005, we reported on the success of Comprehensive School Health
      (CSH) in improving diets, activity levels, and body weights. The successful
      program was recognized as a "best practice" and has inspired the development of
      the Alberta Project Promoting active Living and healthy Eating (APPLE) Schools.
      The project includes 10 schools, most of which are located in socioeconomically
      disadvantaged areas. The present study examines the effectiveness of a CSH
      program adopted from a "best practice" example in another setting by evaluating
      temporal changes in diets, activity levels and body weight. METHODS: In 2008 and
      2010, we surveyed grade 5 students from approximately 150 randomly selected
      schools from the Canadian province of Alberta and students from 10 APPLE Schools.
      Students completed the Harvard Youth/Adolescent Food Frequency Questionnaire,
      questions on physical activity, and had their height and weight measured.
      Multilevel regression methods were used to analyze changes in diets, activity
      levels, and body weight between 2008 and 2010. RESULTS: In 2010 relative to 2008,
      students attending APPLE Schools were eating more fruits and vegetables,
      consuming fewer calories, were more physically active and were less likely obese.
      These changes contrasted changes observed among students elsewhere in the
      province. CONCLUSIONS: These findings provide evidence on the effectiveness of
      CSH in improving health behaviors. They show that an example of "best practice"
      may lead to success in another setting. Herewith the study provides the evidence
      that investments for broader program implementation based on "best practice" are
      justified.

PMID- 22413780
TI  - Multiple intraoral teratoma in a newborn infant: epignathus.
AB  - Teratomas originating from the oral cavity are named as epignathus. It is a rare
      type of teratoma. An 11-day old male newborn was diagnosed with cleft palate and
      intraoral masses. The mass on the right side was protruding from the mouth.
      Another one on the left side was extending from the nasopharynx to the
      oropharynx. The diagnosis of mature teratoma was made based on the
      histopathological study of surgically excised masses. We desired to report on
      this case since multiple localized epignatus in a newborn with cleft palate has
      not been described yet in the literature.

PMID- 22413781
TI  - Conformational transitions of flexible hydrophobic polyelectrolytes in solutions
      of monovalent and multivalent salts and their mixtures.
AB  - Conformations of cationic polyelectrolytes (PEs), a weak poly(2-vinylpyridine)
      (P2VP) and a strong poly(N-methyl-2-vinylpyridinium iodide) (qP2VP), adsorbed on
      mica from saline solutions in the presence of counterions of different valences
      are studied using in situ atomic force microscopy (AFM). Quantitative
      characteristics of chain conformations are analyzed using AFM images of the
      adsorbed molecules. The results of the statistical analysis of the chain contour
      reveal collapse of the PE coils when ionic strength is in a range from tens to
      hundreds of millimoles per kilogram and re-expansion of the coils with a further
      increase of ionic strength up to a region of the saturated saline solutions. The
      competition between monovalent and multivalent counterions simultaneously present
      in solutions strongly affects conformations of PE chains even at a very small
      fraction of multivalent counterions. Shrinkage of PE coils is steeper for
      multivalent counterions than for monovalent counterions. However, the re
      expansion is only incremental in the presence of multivalent counterions.
      Extended adsorbed coils at low salt concentrations and at very high
      concentrations of monovalent salt exhibit conformation corresponding to a 2D coil
      with 0.95 fraction of bound segments (segments in "trains") in the regime of
      diluted surface concentration of the PE. Shrunken coils in the intermediate range
      of ionic strength resemble 3D-globules with 0.8 fraction of trains. The
      incrementally re-expanded PE coils at a high ionic strength remain unchanged at
      higher multivalent salt concentrations up to the solubility limit of the salt.
      The formation of a strong PE complex with multivalent counterions at high ionic
      strength is not well understood yet. A speculative explanation of the observed
      experimental result is based on possible stabilization of the complex due to
      hydrophobic interactions of the backbone.

PMID- 22413783
TI  - Hand-assisted laparoscopic versus total laparoscopic right colectomy: a
      randomized controlled trial.
AB  - AIM: Laparoscopic colectomy for colorectal cancer is associated with definite
      short-term benefits, and is increasingly practised worldwide. The limitations of
      a pure laparoscopic approach include a relative lack of tactile feedback and long
      procedural time. Hand-assisted laparoscopic surgery was introduced in an attempt
      to facilitate operation by improving the tactile sensation. To date, there is no
      consensus as to which approach is better. Herein we conducted a randomized
      controlled trial comparing hand-assisted laparoscopic colectomy (HALC) with total
      laparoscopic colectomy (TLC) in the management of right-sided colonic cancer.
      METHODS: Adult patients with carcinoma of the caecum and ascending colon were
      recruited and randomized to undergo either HALC or TLC. Measured outcomes
      included operative time, blood loss, conversion rate, postoperative morbidities,
      postoperative pain, length of hospital stay, disease recurrence and patient
      survival. RESULTS: Sixty patients (HALC=30, TLC=30) were recruited. The two
      groups were comparable with regard to age, gender distribution, body mass index
      and final histopathological staging. No difference was observed between the
      groups in terms of operating time, conversion rate, operative blood loss, pain
      score and length of hospital stay. With a median follow-up of 27 to 33 months, no
      difference was observed in terms of disease recurrence, and the 5-year survival
      rates remained similar (83%vs 80%, P=0.923). CONCLUSION: HALC is safe and
      feasible, but it does not show any significant benefits over TLC in terms of
      operating time and conversion rate. Routine use of the hand-assisted laparoscopic
      technique in right hemicolectomy is therefore not recommended.

PMID- 22413782
TI  - The Boost study: design of a school- and community-based randomised trial to
      promote fruit and vegetable consumption among teenagers.
AB  - BACKGROUND: The aim of the Boost study was to produce a persistent increase in
      fruit and vegetable consumption among 13-year-olds. This paper describes the
      development, implementation and evaluation of a school-and community-based, multi
      component intervention guided by theory, evidence, and best practice.
      METHODS/DESIGN: We used the Intervention Mapping protocol to guide the
      development of the intervention. Programme activities combined environmental and
      educational strategies and focused on increasing access to fruit and vegetables
      in three settings: School: Daily provision of free fruit and vegetables; a
      pleasant eating environment; classroom curricular activities; individually
      computer tailored messages; one-day-workshop for teachers. Families: school
      meeting; guided child-parent activities; newsletters. Local community: guided
      visits in grocery stores and local area as part of classroom curriculum;
      information sheets to sports-and youth clubs.The Boost study employed a cluster
      randomised controlled study design and applied simple two-stage cluster sampling:
      A random sample of 10 municipalities followed by a random sample of 4 schools
      within each municipality (N = 40 schools). Schools were randomised into a total
      of 20 intervention-and 20 control schools. We included all year 7 pupils except
      those from school classes with special needs. Timeline: Baseline survey: August
      2010. Delivery of intervention: September 2010-May 2011. First follow-up survey:
      May/June 2011. Second follow-up survey: May/June 2012. PRIMARY OUTCOME MEASURES:
      Daily mean intake of fruit and vegetables and habitual fruit and vegetable intake
      measured by validated 24-hour recall-and food frequency questionnaires. SECONDARY
      OUTCOME MEASURES: determinants of fruit and vegetable intake, positive side
      effects and unintended adverse effects. Implementation was monitored by thorough
      process evaluation. DISCUSSION: The baseline data file included 2,156 adolescents
      (95%). There was baseline equivalence between intervention-and control groups for
      sociodemographics, primary outcomes, and availability at home, school and sports
      and youth clubs. Significantly larger proportions of pupils in the control group
      had parents born in Denmark. The study will provide insights into effective
      strategies to increase fruit and vegetable intake among teenagers. The study will
      gain knowledge on implementation processes, intervention effects in population
      subgroups with low intake, and opportunities for including local communities in
      interventions.

PMID- 22413785
TI  - Introduction to the bioequivalence theme issue.

PMID- 22413784
TI  - Combined elemental and biomolecular mass spectrometry imaging for probing the
      inventory of tissue at a micrometer scale.
AB  - Several complementary mass spectrometric imaging techniques allow mapping of
      various analytes within biological tissue sections. Laser ablation inductively
      coupled plasma mass spectrometry (LA-ICPMS) quantitatively detects elements and
      isotopes with very high sensitivity and a particularly high dynamical range.
      Matrix-assisted laser desorption/ionization ion mobility mass spectrometry (MALDI
      IM-MS) allows a pixel-by-pixel classification and identification of biomolecules.
      In order to dispose of the healthy hemisphere as an internal calibrant in
      addition to routinely used external standards, adjacent brain sections of mice
      with a unilateral 6-OHDA lesion of the medial forebrain bundle were chosen as
      exemplary samples. We demonstrate a comprehensive way of data acquisition and
      analysis by coregistering mass spectrometric data on photomicrographs as common
      reference space and thus providing trimodal spatial information. Registering
      subsequent planar element maps yielded continuous 3-dimensional data sets.
      Furthermore, we introduce a correction of MSI data for variable slice thickness
      applicable to all MSI techniques. In the present case, we observed increased
      concentrations of iron, manganese, and copper in the lesioned substantia nigra
      while monounsaturated lipid levels were decreased in the identical region of
      interest. Our techniques provide new insights into the intricate spatial
      relationship of morphology and chemistry within tissue.

PMID- 22413786
TI  - Assessing product bioequivalence for extended-release formulations and drugs with
      long half-lives.
AB  - When a drug product remains in the body for a duration of hours or days,
      estimating the extent of drug exposure is relatively straightforward. For
      immediate release (IR) dosage forms, the peak drug concentration (C(max)) and
      time to peak concentrations (T(max)) are typically adequate for comparing product
      rates of drug absorption. However, unique complexities need to be addressed when
      a drug remains in the system for a duration of months or years. Specifically, if
      the long duration of exposure is attributable to formulation effects, C(max) and
      T(max) may not be adequate to compare the rate of drug absorption, especially
      when there are multiphasic absorption processes. In this case, it may be
      appropriate to use partial (segmented areas) for comparing product profiles.
      However, the decision of how the curves are segmented is not straightforward.
      Points to consider are discussed in this manuscript. Alternatively, if the long
      half-life is due to the pharmacokinetics (PK) of the active pharmaceutical
      ingredient and not to formulation effects, C(max) and T(max) may be appropriate
      metrics for the rate of absorption but decisions regarding the duration of blood
      sampling needed to capture the AUC should be based upon an assessment of the
      inherent variability in drug absorption and elimination. Furthermore, it is
      important to be confident that the absorption phase is complete. In this
      manuscript, we explore some of the difficulties associated with determining
      optimal metrics for comparing the rate and extent of product release for long
      half life drugs when the long duration of exposure is attributable to either the
      inherent drug PK or to formulation effects.

PMID- 22413787
TI  - Estimating product bioequivalence for highly variable veterinary drugs.
AB  - The occurrence of drugs and drug formulations associated with large intrasubject
      pharmacokinetic (PK) variability has been well described in humans and is
      likewise encountered in veterinary medicine. The scaled average bioequivalence
      (SABE) approach adopted by CDER of the FDA for the determination of
      bioequivalence (BE) of highly variable drugs (HVD) needs to be considered when
      applied to veterinary dosage forms. However, because of some of the unique
      challenges that are encountered within the framework of veterinary medicine,
      variations of CDER's approach are presented. The present manuscript discusses HVD
      and highly variable veterinary drugs (HVVD) from the perspective of possible
      alternative approaches to support the assessment of product BE in veterinary
      medicine. Limitations in the use of 3- and 4-way crossover study designs are
      enumerated. In addition to a need for a statistical analysis of HVVD when using a
      parallel study design, the use of the secondary criteria (test-to-reference
      ratio), definition of sigma(0) , and average BE with expanding limits are raised.
      A number of the details need to be finalized, from the selection of a regulatory
      constant to the determination of 'highly variable' in a veterinary drug product.
      Academicians, industrial scientists, and regulators should continue this
      discussion and resolve these details.

PMID- 22413788
TI  - Pharmacokinetics and pharmacodynamics of stereoisomeric drugs with particular
      reference to bioequivalence determination.
AB  - Drugs containing one or more chiral centres exist in stereoisomeric molecular
      forms. Most commonly, drugs containing a single asymmetric carbon atom exist in
      two enantiomeric forms, designated as eutomer (the more potent) and distomer (the
      less potent). As well as differences in potency and other pharmacodynamic
      properties, most members of enantiomeric pairs commonly differ also in their
      pharmacokinetic profiles. This article reviews factors underlying differences in
      pharmacological properties of enantiomers. The relevance of such differences for
      studies designed to evaluate the bioequivalence of products containing chiral
      drugs is also reviewed.

PMID- 22413789
TI  - Demonstrating bioequivalence using clinical endpoint studies.
AB  - For drug products not amenable to blood level studies, clinical endpoint studies
      have been used as an indirect measure of formulation difference in
      bioavailability between test and reference products. However, clinical endpoint
      studies are not as sensitive in detecting formulation differences as blood level
      studies and offer numerous challenges to both regulatory authorities and
      sponsors. The objective of this article is not to suggest new regulatory
      policies, but to explore new methodologies and alternative solutions to clinical
      endpoint bioequivalence (BE) studies, which are used when a blood level study is
      not considered to be appropriate. To achieve this objective, this article
      identifies situations where a clinical endpoint study might be appropriate, lists
      the advantages and disadvantages of this type of study design, and discusses
      possible alternative solutions. It is concluded that future evidence-based
      research is needed to explore new methodologies such as clinical trial
      simulations of various study designs, new statistical methods, and new in vitro
      methods to demonstrate BE.

PMID- 22413790
TI  - Should licking behavior be considered in the bioavailability evaluation of
      transdermal products?
AB  - Antiparasitic drugs, and especially macrocyclic lactones (MLs), are often
      formulated as pour-on products because of their ease of administration,
      convenience, and reduction of stress in treated animals. However, because of self
      and allo-grooming, much of a drug administered transdermally may be systemically
      absorbed via the oral route, creating highly variable pharmacokinetic and
      pharmacodynamic response in treated (and untreated) animals. Testing
      bioequivalence (BE) of pour-on drugs in cattle under laboratory conditions (with
      restricted licking) ignores a major factor of drug disposition of these drugs and
      thus fails to predict therapeutic equivalence in the target population under
      clinical conditions of use. Therefore, the interanimal and intra-animal
      variability associated with licking behavior should be considered as a biological
      fact, rather than a noise that needs to be reduced or eliminated. As a result, it
      is recommended that the BE testing for pour-on products in cattle be conducted by
      evaluating both the mean and distribution of bioavailability parameters between
      the reference and test products when animals are not prevented from allo- and
      self-licking.

PMID- 22413791
TI  - Considerations for extrapolating in vivo bioequivalence data across species and
      routes.
AB  - The purpose of this article is to discuss the numerous species-specific and route
      specific factors that can influence the peak and extent of exposure of an active
      pharmaceutical ingredient as they relate to the demonstration of bioequivalence
      between veterinary drug products (test and reference formulations). Evaluation of
      potential circumstances when species-to-species or route-to-route extrapolations
      of bioequivalence data could be considered is provided, together with suggestions
      for alternative statistical analysis. It is concluded that further research is
      much needed in this area to establish an appropriate scientific basis for across
      species and across-route comparisons.

PMID- 22413792
TI  - Establishing bioequivalence of veterinary premixes (Type A medicated articles).
AB  - a) Key issues concerning Premix (Type A medicated articles) Bioequivalence
      evaluations: 1) This is a complex issue concerning both route of administration
      and formulation. 2) If the animal is not at the bunk/trough, the animal is not
      self-administering (eating medicated feed), thus there can be no drug absorption.
      b) Differing opinions among scientists and regulatory authorities/expert bodies
      regarding: 1) No harmonization on how to design, conduct, and interpret in vivo
      studies. 2) Applicability of biowaivers to Type A (premix) products. 3) Why are
      topdress and complete feed considered differently? Are they different
      formulations or different routes of administration? 4) Single dose vs. multi-dose
      studies. 5) What is the final formulation? c) What are the next steps: 1)
      Harmonize current bioequivalence guidelines through the VICH process. 2)
      Determine the applicability/non-applicability of the Biopharmaceutical
      Classification System (BCS). 3) Establish the Total Mixed Ration (i.e.
      formulation) effects. 4) Define the test subject (individual, pen, etc.).

PMID- 22413793
TI  - Challenges associated with the demonstration of bioequivalence of intramammary
      products in ruminants.
AB  - This article explores the numerous challenges encountered when the goal is to
      demonstrate bioequivalence (BE) between test and reference intramammary (IMM)
      products in ruminants. Numerous pathophysiological factors of mastitis and
      physicochemical properties of IMM formulations are implicated in the difficulties
      in confirming BE for this dosage form. Advantages and disadvantages of current BE
      study designs are discussed, and alternative perspectives are outlined. Ongoing
      and future research increasing our knowledge of the pharmacokinetics and
      pharmacodynamics of antimicrobial drugs delivered through this route is crucial
      to better understanding the implications of clinically significant formulation
      differences in the demonstration of BE and may also help in developing more
      effective IMM formulations for ruminants.

PMID- 22413794
TI  - The scientific basis for establishing solubility criteria for veterinary species.
AB  - The relationship between factors influencing the in vitro and in vivo drug
      solubilization is highly dependent upon the physiology of the individual animal
      species and the physico-chemical properties of the drug. The solubilization of a
      drug in an aqueous medium is controlled by the strength of the interaction
      between a molecule of the active pharmaceutical ingredient (API) and the
      molecules of the solvent. In this regard, the stronger this interaction, the
      greater the likelihood that the drug will go into solution. Counteracting this
      solubilization process is the strength of the affinity of the solute for itself,
      or how tightly bound the compound is to its own solid state form. The stronger
      affinity of a solute for itself, the more difficult it will be for that molecule
      to go into solubility. However, solubility is not a universal value. Rather, it
      should be considered from the perspective of the interactions between the API in
      its solid form and the solution conditions such as: pH, the nature of the primary
      solvent, the presence of co-solvents, the presence of solubilizing additives, the
      ionic strength of the medium, incubation time, and temperature. Each of these
      factors needs to be considered when evaluating potential interspecies differences
      in drug solubility.

PMID- 22413795
TI  - Drug solubility classification in the dog.
AB  - Similar to human drugs, oral drug delivery is a major route of drug
      administration in dogs. Therefore, it is important to consider how the
      physiological characteristics of the dog may influence the considerations that go
      into the classification of drug solubility. In this manuscript, we discuss the
      impact of body size vs. administered dose and gastric volume on the estimated
      gastric drug concentration that needs to be considered. However, when using a
      dose number (Do) paradigm, there are very few drugs for which the different
      methods of estimating gastric volume will alter the drug solubility
      classification. We also evaluate the range of pH values under which a solubility
      assessment should be generated and conclude that despite specific differences in
      the pH values of the gastrointestinal environment of people and dogs, the human
      pH criteria for evaluating drug solubility can be used when evaluating drug
      solubility of oral medications in dogs.

PMID- 22413796
TI  - Drug solubility classification in the bovine.
AB  - Currently, the basis for solubility test conditions and the corresponding
      solubility criteria is derived from the tremendous wealth of information
      developed to support human pharmaceutical product development and regulation.
      However, there are several critical differences between the gastrointestinal
      tract of ruminants and monogastric species that can affect the conditions and
      criteria to be applied to the classification of drug solubility in cattle. These
      include the pH of the stomach, the volume of the stomach, the types of oral
      formulations, and the definition of 'highest dose'. These points are discussed
      below and alternative perspectives for consideration with regard to possible
      modification of solubility criteria for ruminants are presented.

PMID- 22413797
TI  - How do you define equivalence of the API of biomass products?

PMID- 22413798
TI  - Challenges obtaining a biowaiver for topical veterinary dosage forms.
AB  - Obtaining a biowaiver for topical drugs used in veterinary species faces many of
      the same challenges associated with human topicals. However, the skin of domestic
      animals varies anatomically and biochemically and experimental approaches to
      assess bioequivalence (BE) in veterinary species have challenges that are not
      often encountered with human skin. This is especially the situation with locally
      acting drugs. The focus of this paper is to address several of the challenges
      associated with (i) determining the BE of these locally acting drugs and (ii)
      critically examine the current technological advances that can act as a surrogate
      for clinical trials.

PMID- 22413799
TI  - Weight gain in pregnancy: a survey of current practices in a teaching hospital.
AB  - One hundred and three obstetric and midwifery staff at a university teaching
      hospital were surveyed about knowledge and practices with regard to counselling
      women about appropriate gestational weight gain. Seventy-seven percent of staff
      reported advising women about weight gain in pregnancy under some circumstances,
      but only 22% set specific weight or weight gain targets. Seventy-nine percent of
      staff considered their training in this aspect of antenatal care to be
      inadequate. Further education and support of medical and nursing staff are needed
      to ensure guidelines for weight management in pregnancy are optimally
      implemented.

PMID- 22413800
TI  - Recurrent aphthous stomatitis: a review.
AB  - Recurrent aphthous stomatitis (RAS) is a common clinical condition producing
      painful ulcerations in oral cavity. The diagnosis of RAS is based on well-defined
      clinical characteristics but the precise etiology and pathogenesis of RAS remain
      unclear. The present article provides a detailed review of the current concepts
      and knowledge of the etiology, pathogenesis, and management of RAS.

PMID- 22413801
TI  - Development and institutional care.

PMID- 22413802
TI  - Genotypic diversity enhances invasive ability of Spartina alterniflora.
AB  - Although genetic diversity is very important for alien species, which have to
      cope with new environments, little is known about the role that genetic diversity
      plays in their invasive success. In this study, we set up a manipulation
      experiment including three levels of genotypic diversity to test whether
      genotypic diversity can enhance the invasive ability of alien species, in our
      case the invasive Spartina alterniflora in China, and to infer the underlying
      mechanisms. There was no significant relationship between genotypic diversity and
      parameters of performance in the first year; however, from the summer of the
      second year onwards, genotypic diversity enhanced four of the six parameters of
      performance. After two growing seasons, there were significant positive
      relationships between genotypic diversity and maximum spread distance, patch
      size, shoot number per patch, and aboveground biomass. Moreover, abundance of the
      native dominant species Scirpus mariqueter was marginally significantly decreased
      with genotypic diversity of S. alterniflora, suggesting that enhanced invasive
      ability of S. alterniflora may have depressed the growth of the native species.
      There was no significant difference in most measures of performance among six
      genotypes, but we observed a transgressive over performance in four measures in
      multiple-genotype patches. At the end of the experiment, there were significant
      nonadditive effects of genotypic diversity according to Monte Carlo permutations,
      in six-genotype, but not three-genotype plots. Our results indicated that both
      additive and nonadditive effects played roles in the positive relationship
      between genetic diversity and invasion success, and nonadditive effects were
      stronger as duration increased.

PMID- 22413803
TI  - DNA repair system and prostate cancer progression: the role of NBS1 polymorphism
      (rs1805794).
AB  - NBS1 plays an important role in the maintenance of genomic integrity, by being
      involved in cellular response to DNA damage. The NBS1 rs1805794 G>C polymorphism
      has been investigated in several studies, but its function still remains unclear
      due to some controversial results. The present work aimed to evaluate the role of
      this polymorphism in prostate cancer progression, by performing a case-control
      study comparing 239 patients who were diagnosed with early disease to 186 who
      presented advanced disease. We also assessed NBS1 mRNA expression among the
      different groups by quantitative real time (qRT)-polymerase chain reaction. We
      found that the GG carriers presented an almost two fold increased risk for
      advanced prostate disease (odds ratio [OR] = 1.87; confidence interval [CI] =
      1.26-2.79; p = 0.002). Further, high tumor grade (OR = 3.02; CI = 2.32-3.92;
      p<0.001) and high serum prostate specific antigen (PSA) (OR = 6.48; CI = 4.48
      9.38; p<0.001) were consistently associated to advanced disease. Regarding NBS1
      mRNA expression, we did not find any association with the different outcomes nor
      genotypes (p = 0.926; p = 0.894, respectively). Our results suggest for the first
      time that rs1805794 GG genotype appears to be associated with a higher risk for
      advanced prostate cancer, thus, suggesting a possible new role for NBS1 in
      prostate cancer progression.

PMID- 22413804
TI  - Lifestyle intervention for preventing weight gain in young adults: a systematic
      review and meta-analysis of RCTs.
AB  - Younger generations of Australians are gaining weight faster than their parents.
      Associated health consequences are likely to ensue unless weight gains are
      prevented; however, it is unclear how to effectively intervene in this
      population. Electronic databases for health sciences were searched from April to
      the end of August 2011. Nine studies were included in the review, eight in the
      meta-analysis, from 771 abstracts reviewed for eligibility criteria: randomized
      controlled trials of lifestyle interventions, published in English (1980 onward),
      aimed at preventing weight gain among healthy subjects 18-35 years. Mean body
      weight change was the primary outcome. The combined weighted mean change in
      intervention participants was -0.87 kg (95% CI -1.56, -0.18) and in control
      participants 0.86 kg (95% CI 0.14, 1.57). Post hoc meta-regression analyses
      revealed evidence-based interventions of 4 months or longer duration were
      significantly associated with greater weight loss (-1.62 [95% CI -3.21, -0.04], P
      = 0.045). The small number, short duration and large heterogeneity of trials
      means the effectiveness of lifestyle intervention for preventing young adult
      weight gain remains unclear. Future trials conducted over longer periods with
      larger samples are urgently required to develop effective programmes that will
      protect against weight gains in future generations.

PMID- 22413805
TI  - Dornase alpha compared to hypertonic saline for lung atelectasis in critically
      ill patients.
AB  - BACKGROUND: Despite the lack of randomized trials, nebulized Dornase alpha and
      hypertonic saline are used empirically to treat atelectasis in mechanically
      ventilated patients. Our objective was to determine the clinical and radiological
      efficacy of these medications as an adjunct to standard therapy in critically ill
      patients. METHODS: Mechanically ventilated patients with new onset (<48 h) lobar
      or multilobar atelectasis were randomized into three groups: nebulized Dornase
      alpha, hypertonic (7%) saline or normal saline every 12 h. All patients received
      standard therapy, including chest percussion therapy, kinetic therapy, and
      bronchodilators. The primary endpoint was the change in the daily chest X-ray
      atelectasis score. RESULTS: A total of 33 patients met the inclusion criteria and
      were randomized equally into the three groups. Patients in the Dornase alpha
      group showed a reduction of 2.18+/-1.33 points in the CXR score from baseline to
      day 7, whereas patients in the normal saline group had a reduction of 1.00+/-1.79
      points, and patients in the hypertonic saline group showed a score reduction of
      1.09+/-1.51 points. Pairwise comparison of the mean change of the CXR score
      showed no statistical difference between hypertonic saline, normal saline, and
      dornase alpha. Airway pressures as well as oxygenation, expressed as
      PaO(2)/F(I)O(2) and time to extubation also were similar among groups. During the
      study period the rate of extubation was 54% (6/11), 45% (5/11), and 63% (7/11) in
      the normal saline, hypertonic saline, and Dornase alpha groups, respectively
      (p=0.09). No treatment related complications were observed. CONCLUSIONS: There
      was no significant improvement in the chest X-ray atelectasis score in
      mechanically ventilated patients with new onset atelectasis who were nebulized
      with Dornase alpha twice a day. Hypertonic saline was no more effective than
      normal saline in this population. Larger randomized control trials are needed to
      confirm our results.

PMID- 22413806
TI  - Equivalence considerations for orally inhaled products for local action-ISAM/IPAC
      RS European Workshop report.
AB  - The purpose of this article is to document the discussions at the 2010 European
      Workshop on Equivalence Determinations for Orally Inhaled Drugs for Local Action,
      cohosted by the International Society for Aerosols in Medicine (ISAM) and the
      International Pharmaceutical Consortium on Regulation and Science (IPAC-RS). The
      article summarizes current regulatory approaches in Europe, the United States,
      and Canada, and presents points of consensus as well as ongoing debate in the
      four major areas: in vitro testing, pharmacokinetic and pharmacodynamic studies,
      and device similarity. Specific issues in need of further research and discussion
      are also identified.

PMID- 22413808
TI  - Fasting plasma glucose 6-12 weeks after starting insulin glargine predicts
      likelihood of treatment success: a pooled analysis.
AB  - AIMS: To evaluate whether fasting plasma glucose values measured early during
      insulin therapy can identify patients with Type 2 diabetes who may not achieve
      adequate glycaemic control after 6 months and will require additional treatment.
      METHODS: Patient-level data from seven prospective, randomized, controlled
      studies using treat-to-target methods were pooled to evaluate the efficacy of
      insulin glargine. Fasting plasma glucose was measured at baseline, week 6 or 8
      (6/8) and week 12. HbA(1c) was measured at week 24 to assess glycaemic control.
      RESULTS: One thousand and thirty-six patients (56% male, 81% white) were included
      in the analysis (mean age 56.3 years; duration of diabetes 8.4 years). Baseline
      mean fasting plasma glucose was 11.2 mmol/l and mean HbA(1c) was 73 mmol/mol
      (8.8%). After 24 weeks of treatment, mean HbA(1c) decreased to 53 mmol/mol
      (7.0%); 56% of patients reached a target HbA(1c) <= 53 mmol/mol (7.0%).
      Significant correlations with week 24 HbA(1c) were obtained for fasting plasma
      glucose measured at week 6/8 and week 12 (r = 0.32; P < 0.0001 for both).
      Patients with fasting plasma glucose > 10 mmol/l at week 6/8 or week 12 were
      significantly less likely to achieve the HbA(1c) target at the end of treatment
      than patients with fasting plasma glucose < 8.9 mmol/l (P < 0.0001 for both). If
      fasting plasma glucose was > 10 mmol/l at week 6/8 or week 12, patients had only
      a 27% chance of reaching the HbA(1c) goal. CONCLUSIONS: Fasting plasma glucose
      remaining > 10 mmol/l after 6-12 weeks of glargine therapy indicates that
      reaching target HbA(1c) <= 53 mmol/mol (7.0%) is unlikely and calls for
      individualized attention to consider further therapeutic options.

PMID- 22413809
TI  - Epidemiological aspects of non-human antibiotic usage and resistance:
      implications for the control of antibiotic resistance in Ghana.
AB  - OBJECTIVES: To provide insights into the epidemiology of antibiotic usage in
      animal husbandry in Ghana and its effect on resistance. METHODS: Three hundred
      and ninety-five randomly sampled commercial livestock keepers who practised
      intensive or extensive farming were interviewed about their antibiotic usage
      practices using a structured questionnaire. Escherichia coli isolated from stool
      specimens of farmers and their animals were tested against eight antibiotics
      using the Kirby Bauer method. RESULTS: Ninety-eight percent (387) of the farmers
      used antibiotics on animals and the main purpose was to prevent infections in
      animals; 41% applied antibiotics monthly. The overall prevalence of multiple drug
      resistance among the E. coli isolates was 91.6%; rates in human and animal
      isolates were 70.6% and 97.7%, respectively. The prevalence of resistance in
      animal isolates to the various drugs ranged from 60.8% (amikacin) to 95.7%
      (ampicillin); the prevalence of resistance in human isolates to the drugs ranged
      from 2% (cefuroxime) to 94.1% (gentamicin). Animal E. coli isolates showed higher
      resistance than that of human isolates for five of eight drugs tested.
      CONCLUSION: It is concluded that antibiotic usage in animal husbandry in Ghana is
      more driven by the interest of livestock keepers to prevent and treat animal
      infections than growth enhancement. Both animal and human E. coli showed high
      levels of antibiotic resistance, although resistance of animal isolates appeared
      to be higher than that of humans. There is the need for the development of an
      antibiotic-resistance management programme in Ghana that will focus
      simultaneously on human and animal use of antibiotics.

PMID- 22413810
TI  - Ovarian ligament adenomyoma: report of a rare entity with review of the
      literature.
AB  - Adenomyoma is a benign tumor composed of endometrial glands, specialized
      endometrioid stroma, and smooth muscle. These tumors typically originate within
      the uterus. An extrauterine adenomyoma is an extremely rare entity. We present
      the case of a 56-year-old perimenopausal woman with a right adnexal mass,
      diagnosed histopathologically as an ovarian ligament adenomyoma. This report
      documents a fourth case of an extrauterine adenomyoma and only the second case in
      ovarian ligament. The differential diagnosis includes endometrioma,
      leiomyomatosis peritonealis disseminata, uterus-like mass lesion and extrauterine
      leiomyoma with entrapped endometrioid glands and stroma. Two theories for the
      etiology of adenomyoma have been proposed: (i) Mullerian duct fusion defect and
      (ii) metaplasia.

PMID- 22413811
TI  - Paradoxical bulging of muscle after injection of botulinum neurotoxin type A into
      hypertrophied masseter muscle.

PMID- 22413812
TI  - Oxidative stress induced interleukin-32 mRNA expression in human bronchial
      epithelial cells.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by
      airflow obstruction and persistent inflammation in the airways and lung
      parenchyma. Oxidative stress contributes to the pathogenesis of COPD. Interleukin
      (IL)-32 expression has been reported to increase in the lung tissue of patients
      with COPD. Here, we show that IFNgamma upregulated IL-32 expression and that
      oxidative stress augmented IFNgamma-induced-IL-32 expression in airway epithelial
      cells. We further investigated transcriptional regulation responsible for
      IFNgamma induced IL-32 expression in human airway epithelial cells. METHODS:
      Human bronchial epithelial (HBE) cells were stimulated with H2O2 and IFNgamma,
      and IL-32 expression was evaluated. The cell viability was confirmed by MTT
      assay. The intracellular signaling pathways regulating IL-32 expression were
      investigated by examining the regulatory effects of MAPK inhibitors and JAK
      inhibitor after treatment with H2O2 and IFNgamma, and by using a ChIP assay to
      identify transcription factors (i.e. c-Jun, CREB) binding to the IL-32 promoter.
      Promoter activity assays were conducted after mutations were introduced into
      binding sites of c-Jun and CREB in the IL-32 promoter. IL-32 expression was also
      examined in HBE cells in which the expression of either c-Jun or CREB was knocked
      out by siRNA of indicated transcription factors. RESULTS: There were no
      significant differences of cell viability among groups. After stimulation with
      H2O2 or IFNgamma for 48 hours, IL-32 expression in HBE cells was increased by
      IFNgamma and synergistically upregulated by the addition of H2O2. The H2O2
      augmented IFNgamma induced IL-32 mRNA expression was suppressed by a JNK
      inhibitor, but not by MEK inhibitor, p38 inhibitor, and JAK inhibitor I.
      Significant binding of c-Jun and CREB to the IL-32 promoter was observed in the
      IFNgamma + H2O2 stimulated HBE cells. Introducing mutations into the c-Jun/CREB
      binding sites in the IL-32 promoter prominently suppressed its transcriptional
      activity. Further, knocking down CREB expression by siRNA resulted in significant
      suppression of IL-32 induction by IFNgamma and H2O2 in HBE cells. CONCLUSION: IL
      32 expression in airway epithelium may be augmented by inflammation and oxidative
      stress, which may occur in COPD acute exacerbation. c-Jun and CREB are key
      transcriptional factors in IFNgamma and H2O2 induced IL-32 expression.

PMID- 22413813
TI  - Relationships of leisure-time and non-leisure-time physical activity with
      depressive symptoms: a population-based study of Taiwanese older adults.
AB  - BACKGROUND: Limited research has explored the relationship between non-leisure
      time physical activity (NLTPA), including domestic and work-related physical
      activities, with depressive symptoms. This study was designed to elucidate
      independent associations between leisure-time physical activity (LTPA), NLTPA,
      and specific parameters of physical activity (frequency, duration and intensity)
      with depressive symptoms in older adults. METHODS: A total of 2,727 persons aged
      >= 65 years participating in the 2005 Taiwan National Health Interview Survey
      were studied. Depressive symptoms were measured by the Center for Epidemiological
      Studies Depression Scale. Information regarding energy parameters for each type
      of LTPA and NLTPA during the past 2-week period was analyzed. After adjusting for
      socio-demographic variables, lifestyle behaviors and health status, multivariate
      logistic regression models were used to compute adjusted odds ratios (AOR) for
      LTPA and NLTPA for predicting depressive symptoms. RESULTS: LTPA but not NLTPA
      was significantly associated with depressive symptoms. Compared with participants
      expending 2000+ kcal/week through LTPA, the risk of experiencing depressive
      symptoms was significantly higher for those expending 1-999 kcal/week (AOR =
      2.06, 95% CI: 1.25-3.39), and those who expending 0 kcal/week (AOR = 3.72, 95%CI:
      2.28-6.06). Among the three parameters of LTPA (intensity, duration and
      frequency) examined, only intensity was independently associated with depressive
      symptoms. CONCLUSIONS: These findings imply that exercise recommendations for
      older adults should emphasize the importance of higher intensity activity, rather
      than frequency or duration, for improved mental well-being. However, well
      designed prospective cohort studies or intervention trials are needed to confirm
      these findings.

PMID- 22413815
TI  - Twisted mannitol crystals establish homologous growth mechanisms for high-polymer
      and small-molecule ring-banded spherulites.
AB  - D-Mannitol belongs to a large and growing family of crystals with helical
      morphologies (Yu, L. J. Am. Chem. Soc.2003, 125, 6380). Two polymorphs of D
      mannitol, alpha and delta, when grown in the presence of additives such as
      poly(vinylpyrrolidone) (PVP) or D-sorbitol, form ring-banded spherulites composed
      of handed helical fibrils, where the helix axes correspond to the radial growth
      directions. The two polymorphs form helices with opposite senses in the presence
      of PVP but the same sense in the presence of D-sorbitol. The characteristic
      dimensions of the fibrils, including thickness, aspect ratio, and pitch, were
      determined by scanning probe and electron microscopies. These values must form
      the basis of any theory that presupposes what forces give rise to crystal
      twisting, a problem that has been broached but unsettled in the literature of
      polymer crystallization. The interdependence of the rhythmic variations of both
      linear and circular birefringence, as determined by Mueller matrix microscopy,
      informs the cooperative organization of mannitol fibers. The microstructure of
      mannitol ring-banded spherulites compares favorably to that of high polymers and
      is evaluated within the context of current theories of crystal twisting.

PMID- 22413814
TI  - Public support for neonatal screening for Pompe disease, a broad-phenotype
      condition.
AB  - BACKGROUND: Neonatal screening for Pompe disease has been introduced in Taiwan
      and a few U.S. states, while other jurisdictions including some European
      countries are piloting or considering this screening. First-tier screening flags
      both classic infantile and late-onset Pompe disease, which challenges current
      screening criteria. Previously, advocacy groups have sometimes supported expanded
      neonatal screening more than professional experts, while neutral citizens' views
      were unknown. This study aimed to measure support for neonatal screening for
      Pompe disease in the general public and to compare it to support among (parents
      of) patients with this condition. The study was done in the Netherlands, where
      newborns are not currently screened for Pompe disease. Newborn screening is not
      mandatory in the Netherlands but current uptake is almost universal. METHODS: A
      consumer panel (neutral group) and (parents of) patients with Pompe disease
      (Pompe group) were sent information and a questionnaire. Responses were analyzed
      of 555 neutral and 58 Pompe-experienced informants who had demonstrated
      sufficient understanding. RESULTS: 87% of the neutral group and 88% of the Pompe
      group supported the introduction of screening (95% CI of difference -10 to 7%).
      The groups were similar in their moral reasoning about screening and acceptance
      of false positives, but the Pompe-experienced group expected greater benefit from
      neonatal detection of late-onset disease. Multivariate regression analysis
      controlling for demographics confirmed that approval of the introduction of
      screening was independent of having (a child with) Pompe disease. Furthermore,
      respondents with university education, regardless of whether they have (a child
      with) Pompe disease, were more likely to be reluctant about the introduction of
      screening than those with less education, OR for approval 0.29 (95% CI 0.18 to
      0.49, p < 0.001). CONCLUSIONS: This survey suggests a rather high level of
      support for newborn screening for Pompe disease, not only among those who have
      personal experience of the disease but also among the general public in the
      Netherlands. Optional screening on the basis of informed parental consent is
      probably unrealistic, underlining the need for new guidelines to help
      policymakers in their consideration of newborn screening for broad phenotype
      conditions.

PMID- 22413816
TI  - Long-term follow-up after anterior sphincter repair: influence of age on
      functional outcome.
AB  - AIM: Anterior sphincter repair has been advocated for women with anterior
      sphincter defects and faecal incontinence. There have been a number of reports of
      deterioration in functional outcome from anal sphincter repair over the long-term
      and of inferior outcomes in older patients. This study set out to examine these
      issues in a specialist tertiary referral unit. METHOD: Patients having a
      sphincter repair were identified from a prospectively collected database. The
      information within the database was expanded by the use of a postal questionnaire
      and structured review of the case notes. The questionnaire incorporated commonly
      used validated scoring systems as well as subjective questions. RESULTS: One
      hundred and thirteen patients were identified, of whom 66 (58%) responded. Of
      these patients, four had incomplete medical notes, leaving 62 (55%) with both
      returned questionnaires and complete medical notes. Forty-eight (72%) patients
      reported subjective initial improvement in their symptoms, though only 37 (56%)
      believed themselves improved at long-term follow-up (median 8.8 years; range 1.1
      13.6 years). Incontinence and quality of life scores mirrored these patients'
      subjective responses. The median age of those patients reporting a subjective
      improvement at long-term follow-up was 38, compared with 56 in those who thought
      they were not improved (P < 0.001). CONCLUSIONS: Outcome from anal sphincter
      repair deteriorates with time. Subjective outcome is worse in older patients who
      additionally tend to have worse incontinence scores and quality of life measures.

PMID- 22413817
TI  - C-terminal heat shock protein 90 inhibitor decreases hyperglycemia-induced
      oxidative stress and improves mitochondrial bioenergetics in sensory neurons.
AB  - Diabetic peripheral neuropathy (DPN) is a common complication of diabetes in
      which hyperglycemia-induced mitochondrial dysfunction and enhanced oxidative
      stress contribute to sensory neuron pathology. KU-32 is a novobiocin-based, C
      terminal inhibitor of the molecular chaperone, heat shock protein 90 (Hsp90). KU
      32 ameliorates multiple sensory deficits associated with the progression of DPN
      and protects unmyelinated sensory neurons from glucose-induced toxicity.
      Mechanistically, KU-32 increased the expression of Hsp70, and this protein was
      critical for drug efficacy in reversing DPN. However, it remained unclear if KU
      32 had a broader effect on chaperone induction and if its efficacy was linked to
      improving mitochondrial dysfunction. Using cultures of hyperglycemically stressed
      primary sensory neurons, the present study investigated whether KU-32 had an
      effect on the translational induction of other chaperones and improved
      mitochondrial oxidative stress and bioenergetics. A variation of stable isotope
      labeling with amino acids in cell culture called pulse SILAC (pSILAC) was used to
      unbiasedly assess changes in protein translation. Hyperglycemia decreased the
      translation of numerous mitochondrial proteins that affect superoxide levels and
      respiratory activity. Importantly, this correlated with a decrease in
      mitochondrial oxygen consumption and an increase in superoxide levels. KU-32
      increased the translation of Mn superoxide dismutase and several cytosolic and
      mitochondrial chaperones. Consistent with these changes, KU-32 decreased
      mitochondrial superoxide levels and significantly enhanced respiratory activity.
      These data indicate that efficacy of modulating molecular chaperones in DPN may
      be due in part to improved neuronal mitochondrial bioenergetics and decreased
      oxidative stress.

PMID- 22413818
TI  - Knowledge of abortion law and provision of abortion services amongst tertiary
      students in Far North Queensland.
AB  - Abortion is an important health issue for Australian women, yet there are large
      variations across Australia in abortion service provision and in state laws
      regulating abortion practice. We conducted a survey of tertiary students in Far
      North Queensland to ascertain their knowledge of local abortion services and of
      abortion law in Queensland. Important gaps were demonstrated in their knowledge
      of the law and of the availability of abortion services.

PMID- 22413819
TI  - Identical twins with lethal congenital pulmonary airway malformation type 0
      (acinar dysplasia): further evidence of familial tendency.
AB  - We report a case of identical twins with lethal congenital pulmonary airway
      malformation (CPAM) type 0. Twin A expired several hours after birth, and twin B
      was sustained by extra-corporeal membrane oxygenation (ECMO) support; however,
      care was withdrawn from twin B following the autopsy of twin A, which revealed a
      diagnosis of CPAM type 0. Both twins showed pulmonary hypoplasia, histologically
      consistent with CPAM type 0 and pulmonary hypertension. Furthermore, the family
      also had a previous male who presented with pulmonary hypoplasia and respiratory
      failure and died shortly after birth; however, no autopsy was performed to
      confirm a diagnosis of CPAM. Here, in discussing our case, as well as previously
      reported cases, we demonstrate CPAM type 0's high prevalence among females (9:1
      ratio). From the reported cases, it appears that CPAM type 0's tendency to recur
      in families is up to 40%, suggesting an autosomal recessive inheritance pattern.
      However, the actual tendency of familial recurrence is hard to assess due to the
      rarity of the disease and the potential lack of reporting CPAM type 0 cases. To
      our knowledge, our report represents the first description of CPAM type 0 in
      identical twins.

PMID- 22413820
TI  - Pattern shape control for heat treatment purification of electron-beam-induced
      deposition of gold from the Me2Au(acac) precursor.
AB  - Gold structures can be created in a scanning electron microscope (SEM) from the
      Me(2)Au(acac) precursor by direct writing with the electron beam. The as
      deposited purity is usually poor, and a common purification approach is a post
      annealing step that indeed is effective but also induces a volume reduction
      because of carbon loss and an undesirable reconfiguration of the gold structure,
      resulting in the loss of the original shape. We studied the shape change as a
      result of such purification, and to minimize this effect, the application of a
      tantalum and chromium buffer layer was investigated. These buffer materials are
      well-known for their good adhesion properties. We confirm by dedicated SEM,
      atomic force microscopy (AFM), and transmission electron microscopy (TEM)
      analysis that, for the creation of a uniform Au structure, tantalum is a better
      buffer layer material than chromium. Post-annealing of the Au electron-beam
      induced deposition (EBID) patterns for 1 h at 600  degrees C in air resulted in a
      dramatic purity increase (from 8-12 atomic % Au to above 92 atomic % Au). The
      uncovered part of the tantalum layer can be easily etched away, resulting in a
      well-defined, high-purity, gold structure.

PMID- 22413822
TI  - Rheumatology meets hepatology in 2012: a clinician's guideline for TNF inhibitors
      in hepatitis B/C virus carriers.
AB  - Effective and less toxic biologics have revolutionized rheumatology as well as
      hepatology over the last decennia resulting in higher therapeutic goals.
      Traditional disease modifying anti-rheumatic drugs (tDMARDs) failing to achieve a
      quiescent chronic rheumatoid arthritis (RA) or spondylarthropathic arthritis (SA)
      inflammatory disease, nowadays are to be switched into a more potent strategy
      with ultimately a combination of tDMARD plus TNF inhibitors (TNFi) early in
      disease. Patients with previous microbiological infections however present a
      challenge for a modern rheumatologist aiming at complete remission, particularly
      in carriers of viral infections. Hepatologists nowadays, can treat chronic
      hepatitis B and C virus infections effectively with potent antivirals. In the
      current issue an overview is given regarding patients in whom TNFi may be
      indicated, but also have been infected with viral hepatitis.

PMID- 22413823
TI  - Alternative options for DNA-based experimental therapy of beta-thalassemia.
AB  - INTRODUCTION: Beta-thalassemias are caused by more than 200 mutations of the beta
      globin gene, leading to low or absent production of adult hemoglobin.
      Achievements have been made with innovative therapeutic strategies for beta
      thalassemias, based on research conducted at the levels of gene structure,
      transcription, mRNA processing and protein synthesis. AREAS COVERED: The
      objective of this review is to describe the development of therapeutic strategies
      employing viral and non-viral DNA-based approaches for treatment of beta
      thalassemia. EXPERT OPINION: Modification of beta-globin gene expression in beta
      thalassemia cells has been achieved by gene therapy, correction of the mutated
      beta-globin gene and RNA repair. In addition, cellular therapy has been proposed
      for beta-thalassemia, including reprogramming of somatic cells to generate
      induced pluripotent stem cells to be genetically corrected. Based on the concept
      that increased production of fetal hemoglobin (HbF) is beneficial in beta
      thalassemia, DNA-based approaches to increase HbF production have been optimized,
      including treatment of target cells with lentiviral vectors carrying gamma-globin
      genes. Finally, DNA-based targeting of alpha-globin gene expression has been
      applied to reduce the excess of alpha-globin production by beta-thalassemia
      cells, one of the major causes of the clinical phenotype.

PMID- 22413825
TI  - Immunotherapy of breast cancer.
AB  - INTRODUCTION: Immunotherapy of breast cancer has been shown to prevent
      recurrence, improve survival and eliminate breast cancer in humans. AREAS
      COVERED: The reason for this review is to present the current information and the
      prospects for the future of immunotherapy of breast cancer in humans to include
      tumor antigens for vaccines and targets for monoclonal antibodies and adoptive T
      cell therapy, and immune modulatory agents, such as adjuvants to stimulate the
      immune response and inhibitors of checkpoint blockade to prevent downmodulation
      of activated lymphocytes, to enhance these modalities. The research discussed and
      the literature search undertaken is of the clinical immunotherapy of breast
      cancer in humans, from 2000 to September, 2011. EXPERT OPINION: The key message
      of the paper is that one reason for the failure of the immune system to control
      macroscopic disease is that the immune escape mechanisms involving both tumor and
      the tumor stroma prevent the immune system from destroying the tumor. Changing
      the tumor microenvironment is necessary to eliminate macroscopic tumors.
      Prospects for improvement are proposals for combining current modalities of
      therapy with type 1 cellular immunity-inducing agents, all targeting multiple
      tumor antigens and in the context of minimal disease.

PMID- 22413824
TI  - Poxviral vectors for cancer immunotherapy.
AB  - INTRODUCTION: Poxviral vaccines have been given to over 1 billion people in the
      successful global eradication of smallpox. Recombinant poxviruses have been
      investigated extensively as a novel immunotherapy for cancer, undergoing several
      iterations to optimize their immunogenicity and efficacy. The current platform
      expressing multiple costimulatory molecules plus a tumor-associated antigen such
      as PSA, that is, PSA-TRICOM (PROSTVAC-V/F), is promising and is currently in a
      Phase III randomized, placebo-controlled clinical trial in metastatic castration
      resistant prostate cancer. AREAS COVERED: This review discusses the clinical
      development of poxviral-based cancer vaccines, with a particular focus on the
      rationale for combining vaccines with other treatment modalities, including
      radiotherapy, chemotherapy, hormonal therapy, other immune-based therapies and
      molecularly targeted therapy. We also discuss the importance of appropriate
      patient selection in clinical trial design. EXPERT OPINION: Preclinical and early
      clinical studies employing poxviral-vector vaccines have shown promising results
      with this novel immunologic approach, both alone and combined with other
      therapies. The challenges of translating the science of immunotherapy to clinical
      practice include clinical trial design that includes appropriate patient
      selection, appropriate end points and identification of meaningful surrogate
      biomarkers.

PMID- 22413826
TI  - The role of  cetuximab  in the management of head and neck cancers.
AB  - INTRODUCTION: The standard of care for patients with locally-advanced head and
      neck cancer is chemoradiation or surgical resection followed by radiation
      treatment with or without chemotherapy and despite aggressive, multimodality
      therapies with their associated toxicities, attempts are being made to improve
      efficacy while reducing toxicity. Cetuximab is a chimeric mAb directed against
      the EGFR that showed clinical activity in squamous cell carcinoma of head and
      neck (SCCHN). AREAS COVERED: Cetuximab is beneficial in recurrent and metastatic
      setting, as well as in the definitive setting. In a landmark study by Bonner et
      al., cetuximab was found to be effective in prolonging survival in conjunction
      with radiation treatment in locally-advanced tumors versus radiation therapy
      alone. The Erbitux in First-Line Treatment of Recurrent or Metastatic Head and
      Neck Cancer (EXTREME) trial also showed an improvement in conjunction with
      chemotherapy in recurrent and metastatic tumors. EXPERT OPINION: Cetuximab is an
      important therapeutic option in SSCHN, and will continue to be used in metastatic
      and definitive settings. While cetuximab is a valuable tool in the treatment of
      SCCHN, more studies are needed to maximize the efficacy of this mAb in clinical
      settings and to identify the subpopulation of patients that truly benefit from
      its use.

PMID- 22413827
TI  - Eculizumab  for treatment of asthma.
AB  - INTRODUCTION: Asthma is an inflammatory disease, which can be exacerbated by
      stimuli such as viral infections and exposure to allergens. Asthma continues to
      be a profound public health problem due to asthma exacerbation in a low
      proportion of patients in need of more effective medications. AREAS COVERED: The
      C5 complement pathway has been proposed as a new target for the treatment of
      asthma, supported by clinical observations of increased C5a levels in asthmatic
      airways, constitutive expression of C5 receptors on bronchial epithelium and
      smooth muscle cells, and preclinical studies in mice demonstrating inhibition of
      C5 cleavage reduced established airway inflammation and improves lung function.
      Eculizumab is a monoclonal antibody, which binds to the complement protein C5,
      thereby preventing the formation of C5a and C5b-9. The research discussed in this
      review describes development of eculizumab for the treatment of paroxysmal
      nocturnal hemoglobinuria and the efficacy of eculizumab on allergen-induced
      asthmatic responses in a placebo-controlled study. EXPERT OPINION: In an allergen
      challenge model of asthma, there was a significant period effect with eculizumab,
      with inhibition of the late asthmatic response in subjects who received placebo
      treatment first. Although this study provides some evidence that eculizumab may
      be effective to attenuate allergen-induced responses, the role of C5 in asthma
      remains to be clarified.

PMID- 22413828
TI  - Effect of polymerized human placenta hemoglobin on hemodynamic parameter and
      cardiac function in a rat hemorrhagic shock model.
AB  - To investigate whether polymerized human placenta hemoglobin (PolyPHb) improved
      hemodynamic parameter recovery and cardiac function after hemorrhagic shock, a
      mean arterial pressure (MAP) of 30 mmHg was maintained for 60min. Then, all the
      rats were randomly resuscitated with hetastarch (HES), shed blood (Whole Blood),
      or PolyPHb (PolyPHb). The MAP was greatly improved by PolyPHb, but it was still
      lower than that of the Whole Blood group. Meanwhile, the cardiac function and
      enzyme releases in the PolyPHb group were similar to the HES group. Therefore,
      our findings suggest that PolyPHb moderately improved hemodynamic recovery and
      provided little cardioprotective effect in hemorrhagic shock.

PMID- 22413829
TI  - Clinical characteristics and risk factors for septic shock in patients receiving
      emergency drainage for acute pyelonephritis with upper urinary tract calculi.
AB  - BACKGROUND: Acute pyelonephritis (APN) is a common complication of ureteral
      obstruction caused by urolithiasis, and it can be lethal if it progresses to
      septic shock. We investigated the clinical characteristics of patients undergoing
      emergency drainage and assessed risk factors for septic shock. METHODS: A
      retrospective study was performed of 98 patients (101 events) requiring emergency
      drainage at our urology department for obstructive APN associated with upper
      urinary tract calculi from January 2003 to January 2011. Clinical characteristics
      were summarized, and risk factors for septic shock were assessed by logistic
      regression analysis. RESULTS: Objective evidence of sepsis was found in 64
      (63.4%) events, and 21 events (20.8%) were categorized as septic shock. Ninety
      six patients recovered, but 2 patients died of septic shock. Multivariate
      analysis revealed that age and the presence of paralysis were independent risk
      factors for septic shock. CONCLUSIONS: APN associated with upper urinary tract
      calculi is a severe disease that should be treated with caution, particularly
      when risk factors are present.

PMID- 22413830
TI  - A long-term analysis evaluating the cost-effectiveness of biphasic insulin lispro
      mix 75/25 and mix 50/50 versus long-acting basal insulin analogs in the United
      States.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of biphasic insulin lispro mix
      75/25 (LM75/25) and mix 50/50 (LM50/50) compared with a long-acting analog
      insulin (LAAI) regimen from the perspective of a US healthcare payer. METHODS: A
      published computer simulation model of diabetes was used to evaluate the cost
      effectiveness of LM75/25 and LM50/50 vs a LAAI (insulin glargine) from the
      perspective of a US healthcare payer. Treatment effects in terms of HbA1c
      benefits were taken from a recent meta-analysis. Direct medical costs including
      pharmacy, complication, and patient management costs were obtained from published
      sources. All costs were expressed in 2010 US dollars and future costs and
      clinical benefits were discounted at 3% per annum. Sensitivity analyses were
      performed. RESULTS: LM75/25 and LM50/50 were associated with improvements in life
      expectancy of 0.08 and 0.09 years, improvements in quality-adjusted life
      expectancy of 0.07 quality-adjusted life years (QALYs) and 0.08 QALYs and
      increases in cost of US$ 1724 and US$ 1720, respectively, when compared with
      LAAI. LIMITATIONS: The base case analysis did not capture mild or serious
      hypoglycemia on the grounds that the hypoglycemia rate odds ratios failed to
      reach statistical significance in the meta-analysis. In addition, the baseline
      cohort characteristics were based on an insulin-naive population, as opposed to
      the cohorts in the meta-analysis, which were heterogeneous with regard to insulin
      treatment history. CONCLUSIONS: Based on a recently published meta-analysis,
      biphasic analog insulins are likely to improve clinical outcomes and reduce costs
      vs LAAIs in the long-term treatment of type 2 diabetes patients in the US.

PMID- 22413831
TI  - The prevalence of urinary incontinence 20 years after childbirth: a national
      cohort study in singleton primiparae after vaginal or caesarean delivery.
AB  - OBJECTIVE: To investigate the prevalence and risk factors for urinary
      incontinence (UI) 20 years after one vaginal delivery or one caesarean section.
      DESIGN: Registry-based national cohort study. SETTING: Women who returned postal
      questionnaires (response rate 65.2%) in 2008. POPULATION: Singleton primiparae
      who delivered in the period 1985-1988 with no further births (n = 5236). METHODS:
      The Swedish Pregnancy, Obesity and Pelvic Floor (SWEPOP) study linked Medical
      Birth Register (MBR) data to a questionnaire about UI. MAIN OUTCOME MEASURES:
      Prevalence of UI and UI for more than 10 years (UI > 10 years) were assessed 20
      years after childbirth. RESULTS: The prevalence of UI (40.3 versus 28.8%; OR
      1.67; 95% CI 1.45-1.92) and UI > 10 years (10.1 versus 3.9%; OR 2.75; 95% CI 2.02
      3.75) was higher in women after vaginal delivery than after caesarean section.
      There was no difference in the prevalence of UI or UI > 10 years after an acute
      caesarean section or an elective caesarean section. We found an 8% increased risk
      of UI per current body mass index (BMI) unit, and age at delivery increased the
      UI risk by 3% annually. CONCLUSIONS: Two decades after one birth, vaginal
      delivery was associated with a 67% increased risk of UI, and UI > 10 years
      increased by 275% compared with caesarean section. Our data indicate that it is
      necessary to perform eight or nine caesarean sections to avoid one case of UI.
      Weight control is an important prophylactic measure to reduce UI. Current BMI was
      the most important BMI-determinant for UI, which is important, as BMI is
      modifiable.

PMID- 22413832
TI  - Haemoglobin A(1c) , acute hyperglycaemia and short-term prognosis in patients
      without diabetes following acute ST-segment elevation myocardial infarction.
AB  - AIMS: To assess the prognostic impact of HbA(1c) and blood glucose level in
      patients with acute ST-segment elevation myocardial infarction and without
      diabetes. The relationship between HbA(1c) and acute hyperglycaemia was also
      explored. METHODS AND RESULTS: We evaluated 4793 ST-segment elevation myocardial
      infarction patients with baseline HbA(1c) and three glucose measurements in the
      first 24 h. First, patients were stratified into quintiles by HbA(1c) and
      mean/admission glucose level. A total of 373 deaths (7.8%) occurred at 7 days,
      and 486 deaths (10.1%) occurred at 30 days. There were no significant differences
      in 7- and 30-day mortality, and major adverse cardiovascular event rates across
      HbA(1c) quintiles (< 34.4 mmol/mol (5.3% ), 34.4 to < 37.7 mmol/mol (5.6%), 37.7
      to < 41.0 mmol/mol (5.9% ), 41.0 to < 47.5 mmol/mol (6.5%), and >= 47.5 mmol/mol;
      P for trend > 0.05). The risks of mortality and major adverse cardiovascular
      events were significantly increased in patients with higher glucose quintiles and
      lower quintile compared with the middle quintile after multivariable adjustment
      (P < 0.001). Patients were then reclassified into four groups according to
      mean/admission glucose and HbA(1c) levels. The group with elevated glucose and
      non-elevated HbA(1c) was associated with the highest mortality and major adverse
      cardiovascular event risk (P < 0.001). CONCLUSIONS: Unlike acute hyperglycaemia,
      an elevated HbA(1c) level was not a risk factor for short-term outcomes in ST
      segment elevation myocardial infarction patients without diabetes. Patients with
      acute hyperglycaemia and non-elevated HbA(1c) were associated with the worst
      prognosis. That suggests chronic glycaemic control/HbA(1c) level may help to
      recognize stress-induced hyperglycaemia and identify high-risk patients.

PMID- 22413833
TI  - Risk factors of treatment discontinuation due to uterine bleeding in adenomyosis
      patients treated with dienogest.
AB  - AIM: Adenomyosis patients treated with dienogest are considered to be at higher
      risk of uterine bleeding; however, the mechanisms which cause severe uterine
      bleeding in those patients are unknown. This study aims to investigate the risk
      factors of uterine bleeding among adenomyosis patients treated with dienogest.
      MATERIAL AND METHODS: Clinical data of 51 adenomyosis patients treated with
      dienogest were retrospectively collected from their medical records. The impact
      of potential risk factors (age, sagittal square area of the uterus before
      treatment, and estradiol at the third month of treatment) and confounders
      (hemoglobin before treatment and prior medical treatments) on the time to
      treatment discontinuation due to uterine bleeding was assessed using log-rank
      tests and a Cox proportional hazard model. RESULTS: Age (< 38 years, P = 0.004),
      hemoglobin before treatment (<12 g/dL, P = 0.047), and estradiol at the third
      month of treatment (>= 60 pg/mL, P = 0.027) had statistically significant effects
      on the time to treatment discontinuation due to uterine bleeding. Age was still
      statistically significant after controlling for hemoglobin (P = 0.023).
      CONCLUSION: Adenomyosis patients treated with dienogest are at higher risk of
      treatment discontinuation due to uterine bleeding, especially when they are of
      younger age, have anemia before treatment, and/or have mildly suppressed or
      unsuppressed estradiol after they started dienogest treatment. Clinicians should
      pay special attention when they prescribe dienogest for such patients.

PMID- 22413834
TI  - Rural electrification in Brazil and implications for schistosomiasis
      transmission: a preliminary study in a rural community in Minas Gerais State,
      Brazil.
AB  - OBJECTIVES: To evaluate the potential transmission of Schistosoma mansoni through
      well water pumped into households in a rural Brazilian community within the
      context of Brazil's rural electrification program Luz Para Todos (Light for All).
      METHODS: All households were interviewed about their water facilities and
      domestic water use, all household members were examined for S. mansoni infections
      and positives treated, and malacological and water contact studies were performed
      between 2001 and 2009. RESULTS: Thirty-one of the 142 households in the Virgem
      das Gracas study area owned wells with electric pumps in 2009, vs. no wells in
      2001, and the number of water storage tanks increased from 85 to 131. The
      potential for schistosomiasis transmission through piped well water was indicated
      by the recovery of Biomphalaria gabrata, including S. mansoni-infected snails,
      from wells, the presence of Biomphalaria in tanks and the ability of S. mansoni
      cercariae to remain infective for considerable distances in flowing water.
      However, access to well water was not associated with higher S. mansoni infection
      rates. CONCLUSIONS: Our results indicate that further studies are needed to
      determine the infectivity of well water and its impact on schistosomiasis
      transmission.

PMID- 22413835
TI  - Migration induced by epidermal and hepatocyte growth factors in oral squamous
      carcinoma cells in vitro: role of MEK/ERK, p38 and PI-3 kinase/Akt.
AB  - BACKGROUND: Cell migration is a necessary part of malignant invasiveness. Oral
      squamous cell carcinomas (OSCC) have a great tendency for local invasive growth.
      We have investigated signalling pathways involved in cell migration induced by
      epidermal growth factor (EGF) and hepatocyte growth factor (HGF) in OSCC cells
      and examined the effects of various experimental and clinically approved anti
      tumour signal inhibitors on the migratory activity. METHODS: Migration was
      studied in three human OSCC cell lines, using a scratch wound assay in vitro and
      time-lapse cinematography. Specific phosphorylation of signalling proteins was
      assessed by Western blotting. RESULTS: In the E10 cell line, EGF and HGF induced
      phosphorylation of EGF receptor (EGFR) and Met, respectively, phosphorylation of
      ERK1/2, p38 and Akt, and dose-dependent activation of cell migration. Addition of
      the EGFR-specific inhibitors cetuximab (antibody) or gefitinib (tyrosine kinase
      blocker) abolished cell migration elicited by EGF. Similarly, a Met kinase
      inhibitor (SU11274) blocked HGF-induced cell migration. Furthermore, when three
      cell lines were treated with blockers of the MEK/ERK, p38 or the PI-3 kinase/Akt
      pathways, the migratory response to both EGF and HGF was inhibited, but to
      varying degrees. Notably, in E10 and D12 cells, HGF-induced migration was
      particularly sensitive to PI-3 K-inhibition, while in C12 cells, both HGF- and
      EGF-induced migration were highly sensitive to p38-blockade. CONCLUSION: The
      results demonstrate that the MEK/ERK, p38 and PI-3 kinase pathways are all
      involved in mediating the increased migration in OSCC cell lines induced by EGF
      and HGF, but their relative importance and the effects of specific signal
      inhibitors differ.

PMID- 22413837
TI  - Naphtho[2,1-b:6,5-b']difuran: a versatile motif available for solution-processed
      single-crystal organic field-effect transistors with high hole mobility.
AB  - We here report naphtho[2,1-b:6,5-b']difuran derivatives as new p-type
      semiconductors that achieve hole mobilities of up to 3.6 cm(2) V(-1) s(-1) along
      with high I(on)/I(off) ratios in solution-processed single-crystal organic field
      effect transistors. These features originate from the dense crystal packing and
      the resulting large intermolecular pi-orbital overlap as well as from the small
      reorganization energy, all of which originate from the small radius of an oxygen
      atom.

PMID- 22413836
TI  - Power to identify a genetic predictor of antihypertensive drug response using
      different methods to measure blood pressure response.
AB  - BACKGROUND: To determine whether office, home, ambulatory daytime and nighttime
      blood pressure (BP) responses to antihypertensive drug therapy measure the same
      signal and which method provides greatest power to identify genetic predictors of
      BP response. METHODS: We analyzed office, home, ambulatory daytime and nighttime
      BP responses in hypertensive adults randomized to atenolol (N = 242) or
      hydrochlorothiazide (N = 257) in the Pharmacogenomic Evaluation of
      Antihypertensive Responses Study. Since different measured BP responses may have
      different predictors, we tested the "same signal" model by using linear
      regression methods to determine whether known predictors of BP response depend on
      the method of BP measurement. We estimated signal-to-noise ratios and compared
      power to identify a genetic polymorphism predicting BP response measured by each
      method separately and by weighted averages of multiple methods. RESULTS: After
      adjustment for pretreatment BP level, known predictors of BP response including
      plasma renin activity, race, and sex were independent of the method of BP
      measurement. Signal-to-noise ratios were more than 2-fold greater for home and
      ambulatory daytime BP responses than for office and ambulatory nighttime BP
      responses and up to 11-fold greater for weighted averages of all four methods.
      Power to identify a genetic polymorphism predicting BP response was directly
      related to the signal-to-noise ratio and, therefore, greatest with the weighted
      averages. CONCLUSION: Since different methods of measuring BP response to
      antihypertensive drug therapy measure the same signal, weighted averages of the
      BP responses measured by multiple methods minimize measurement error and optimize
      power to identify genetic predictors of BP response.

PMID- 22413838
TI  - Is female preference for large sexual ornaments due to a bias to escape predation
      risk?
AB  - BACKGROUND: A female preference for intense sexual visual signals is widespread
      in animals. Although the preferences for a signal per se and for the intensity of
      the signal were often regarded to have the identical origin, no study has
      demonstrated if this is true. It was suggested that the female fiddler crabs
      prefer males with courtship structures because of direct benefit to escape
      predation. Here we tested if female preference for both components (i.e. presence
      and size) of the courtship structure in Uca lactea is from the sensory bias to
      escape predation. If both components have the identical origin, females should
      show the same response to different-sized courtship structures regardless of
      predation risk. RESULTS: First, we observed responses of mate-searching female U.
      lactea to courting males with full-sized, half-sized and no semidomes which were
      experimentally manipulated. Females had a directional preference for males with
      bigger semidomes within normal variation. Thereafter, we tested the effect of
      predation risk on the female bias in the non-courtship context. When threatened
      by an avian mock predator, females preferentially approached burrows with full
      sized semidomes regardless of reproductive cycles (i.e. reproductive periods and
      non-reproductive periods). When the predator cue was absent, however, females
      preferred burrows with semidomes without discriminating structure size during
      reproductive periods but did not show any bias during non-reproductive periods.
      CONCLUSIONS: Results indicate that selection for the size of courtship structures
      in U. lactea may have an origin in the function to reduce predation risk, but
      that the preference for males with structures may have evolved by female choice,
      independent of predation pressure.

PMID- 22413839
TI  - A case-control study of Burkitt lymphoma in East Africa: are local health
      facilities an appropriate source of representative controls?
AB  - BACKGROUND: We investigated the feasibility and appropriateness of enrolling
      controls for Burkitt lymphoma (BL) from local health facilities in two regions in
      Uganda. METHODS: BL case data were compiled from two local hospitals with
      capacity to diagnose and treat BL in North-west and North-central regions of
      Uganda during 1997 to 2009. Local health facility data were compiled from
      children attending four representative local health facilities in the two regions
      over a two week period in May/June 2010. Age and sex patterns of BL cases and
      children at local facilities were compared and contrasted using frequency tables.
      RESULTS: There were 999 BL cases diagnosed in the study area (92% of all BL cases
      treated at the hospitals): 64% were from North-central and 36% from North-west
      region. The mean age of BL cases was 7.0 years (standard deviation [SD] 3.0).
      Boys were younger than girls (6.6 years versus 7.2 years, P = 0.004) and cases
      from North-central region were younger than cases from North-west region (6.8
      years versus 7.3 years, P = 0.014). There were 1012 children recorded at the four
      local health facilities: 91% at facilities in North-central region and 9% from
      facilities in North-west region. Daily attendance varied between 1 to 75 children
      per day. The mean age of children at health facilities was 2.2 years (SD 2.8); it
      did not differ by sex. Children at North-central region facilities were younger
      than children at North-west region facilities (1.8 years versus 6.6 years, P <
      0.001). CONCLUSIONS: While many children attend local health facilities,
      confirming feasibility of obtaining controls, their mean age is much lower than
      BL cases. Health facilities may be suitable for obtaining young, but not older,
      controls.

PMID- 22413840
TI  - Role of Gly117 in the cation/melibiose symport of MelB of Salmonella typhimurium.
AB  - The melibiose permease of Salmonella typhimurium (MelB(St)) catalyzes symport of
      melibiose with Na(+), Li(+), or H(+), and bioinformatics analysis indicates that
      a conserved Gly117 (helix IV) is part of the Na(+)-binding site. We mutated
      Gly117 to Ala, Pro, Trp, or Arg; the effects on melibiose transport and binding
      of cosubstrates depended on the physical-chemical properties of the side chain.
      Compared with WT MelB(St), the Gly117 -> Ala mutant exhibited little difference
      in either cosubstrate binding or stimulation of melibiose transport by Na(+) or
      Li(+), but all other mutations reduced melibiose active transport and efflux, and
      decreased the apparent affinity for Na(+). The bulky Trp at position 117 caused
      the greatest inhibition of melibiose binding, and Gly117 -> Arg yielded less than
      a 4-fold decrease in the apparent affinity for melibiose at saturating Na(+) or
      Li(+) concentration. Remarkably, the mutant Gly117 -> Arg catalyzed melibiose
      exchange in the presence of Na(+) or Li(+), but did not catalyze melibiose
      translocation involving net flux of the coupling cation, indicating that sugar is
      released prior to release of the coupling cation. Taken together, the findings
      are consistent with the notion that Gly117 plays an important role in cation
      binding and translocation.

PMID- 22413841
TI  - Nurse-delivered universal point-of-care testing for HIV in an open-access
      returning traveller clinic.
AB  - BACKGROUND: Early diagnosis of HIV infection reduces morbidity and mortality
      associated with late presentation. Despite UK guidelines, the HIV testing rate
      has not increased. We have introduced universal HIV screening in an open-access
      returning traveller clinic. METHODS: Data were prospectively recorded for all
      patients attending the open-access returning traveller clinic between August 2008
      and December 2010. HIV testing was offered to all patients from May 2009;
      initially testing with laboratory samples (phase 1) and subsequently a point-of
      care test (POCT) (phase 2). RESULTS: A total of 4965 patients attended the
      clinic; 1342 in phase 0, 792 in phase 1 and 2831 in phase 2. Testing rates for
      HIV increased significantly from 2% (38 of 1342) in phase 0 to 23.1% (183 of 792)
      in phase 1 and further increased to 44.5% (1261 of 2831) during phase 2 (P <
      0.0001). Two new diagnoses of HIV-1 were identified in phase 1 (1.1% of tested);
      seven patients had a reactive POCT test in phase 2, of whom five (0.4% of those
      tested) were confirmed in a 4th generation assay. The patients with false
      reactive tests had a concurrent Plasmodium falciparum infection. Patients
      travelling to the Middle East and Europe were less likely to accept an HIV test
      with POCT. CONCLUSIONS: A nurse-delivered universal point-of-care HIV testing
      service has been successfully introduced and sustained in an acute medical clinic
      in a low-prevalence country. Caution is required in communicating reactive
      results in low-prevalence settings where there may be alternative diagnoses or a
      low population prevalence of HIV infection.

PMID- 22413842
TI  - Giant congenital nevus with plexiform neurofibroma and malignant peripheral nerve
      sheath tumor.
AB  - A female patient with a giant congenital nevus associated with plexiform
      neurinoma and malignant peripheral nerve sheath tumor (MPNST) on head and neck is
      presented. We theoretically discuss possibilities of mutual origin all three
      entities, including the Boland theory of neurochristopaty. The clinical,
      surgical, and histologic aspects of the disease are discussed. Only one similar
      case in written literature was described.

PMID- 22413843
TI  - Married men's first time experiences of early childbearing and their role in
      sexual and reproductive decision making: a qualitative study from rural Vietnam.
AB  - Male partners' involvement in women's sexual and reproductive health has been
      increasingly emphasised in international health. A qualitative approach with open
      ended qualitative interviews was used to explore young, married men's first time
      experiences of early childbearing, their sexual and reproductive decision making
      and the meanings they make of their role as husbands and fathers. The results
      offer a nuanced picture of the men's vulnerability in becoming young fathers and
      having to assume their role as family decision-makers, while still being
      inexperienced in matters related to the health of their wives and newborn child.
      Constraints to gender equality and traditional norms and values continue to pose
      barriers to both young men and women making independent decisions in relation to
      marriage and childbearing. Men's involvement is necessary in healthcare
      programmes designed to improve women's sexual and reproductive health and the
      health of the newborn. Young, first-time fathers, in particular, need support and
      empowerment.

PMID- 22413844
TI  - Double vertical compression sutures: A novel conservative approach to managing
      post-partum haemorrhage due to placenta praevia and atonic bleeding.
AB  - Compression has been regarded as the main haemostatic mechanism of compression
      sutures; however, we suggest that reduced uterine blood flow may be another
      important action. We suggest that our 'double vertical compression sutures' may
      have dual actions: haemostatic compression of the bleeding surface and reduced
      uterine blood flow.

PMID- 22413845
TI  - A new strategy for detection and development of tractable telomerase inhibitors.
AB  - Despite intense academic and industrial efforts and innumerable in vitro and cell
      studies, no small-molecule telomerase inhibitors have emerged as drugs.
      Insufficient understanding of enzyme structure and mechanisms of interdiction
      coupled with the substantial complexities presented by its dimeric composition
      have stalled all progress toward small-molecule therapeutics. Here we challenge
      the assumption that human telomerase provides the best platform for inhibitor
      development by probing a monomeric  Tetrahymena  telomerase with six tool
      compounds. We find BIBR-1532 (2) and MST-312 (5) inhibit only human telomerase,
      whereas beta-R (1), THyF (3), TMPyP4 (6), and EGCG (4) inhibit both enzymes. Our
      study demonstrates that some small-molecule scaffolds can be easily surveyed with
      in vitro studies using  Tetrahymena  telomerase, a finding that could lead to
      more tractable inhibitors with a greater potential for development given the more
      precise insights that can be gleaned from this more easily expressed and assayed
      monomeric enzyme.

PMID- 22413846
TI  - Alterations of global histone H4K20 methylation during prostate carcinogenesis.
AB  - BACKGROUND: Global histone modifications have been implicated in the progression
      of various tumour entities. Our study was designed to assess global methylation
      levels of histone 4 lysine 20 (H4K20me1-3) at different stages of prostate cancer
      (PCA) carcinogenesis. METHODS: Global H4K20 methylation levels were evaluated
      using a tissue microarray in patients with clinically localized PCA (n = 113),
      non-malignant prostate disease (n = 27), metastatic hormone-naive PCA (mPCA, n =
      30) and castration-resistant PCA (CRPC, n = 34). Immunohistochemistry was
      performed to assess global levels of H4K20 methylation levels. RESULTS: Similar
      proportions of the normal, PCA, and mPCA prostate tissues showed strong H4K20me3
      staining. CRPC tissue analysis showed the weakest immunostaining levels of
      H4K20me1 and H4K20me2, compared to other prostate tissues. H4K20me2 methylation
      levels indicated significant differences in examined tissues except for normal
      prostate versus PCA tissue. H4K20me1 differentiates CRPC from other prostate
      tissues. H4K20me1 was significantly correlated with lymph node metastases, and
      H4K20me2 showed a significant correlation with the Gleason score. However, H4K20
      methylation levels failed to predict PSA recurrence after radical prostatectomy.
      CONCLUSIONS: H4K20 methylation levels constitute valuable markers for the dynamic
      process of prostate cancer carcinogenesis.

PMID- 22413847
TI  - Liposomes in cosmeceutics.
AB  - INTRODUCTION: Cosmeceuticals are cosmetic products with biologically active
      ingredients purporting to have medical or drug-like benefits. Some cosmeceuticals
      can act effectively when reaching their target sites in the deeper layers of the
      skin. However, the barrier nature of skin causes significant difficulties for
      compounds to be delivered through. Therefore, scientists are investigating
      various strategies to overcome these barrier properties. Liposomes have been
      claimed to improve the topical delivery of compounds. AREAS COVERED: This paper
      offers a brief overview of current approaches in the research and development of
      liposomal formulations to improve the performance of cosmeceuticals, from recent
      literature. This review deals with the potential of liposomes as a skin delivery
      system for cosmeceuticals, with a focus on the clinical application of liposomes.
      EXPERT OPINION: Liposomes are well-known vesicular cosmetic delivery systems. The
      topical application of liposomes offers a wide range of advantages including
      increased moisturization, restoring action, biodegradability, biocompatibility
      and extended and slow dermal release. Their similar structure to biological
      membranes allows penetration into the epidermal barrier, compared with other
      delivery systems. The incorporation of cosmeceuticals using suitable delivery
      systems is important in the management of cosmetic disorders.

PMID- 22413848
TI  - 13C pulse-labeling assessment of the community structure of active fungi in the
      rhizosphere of a genetically starch-modified potato (Solanum tuberosum) cultivar
      and its parental isoline.
AB  - * The aim of this study was to gain understanding of the carbon flow from the
      roots of a genetically modified (GM) amylopectin-accumulating potato (Solanum
      tuberosum) cultivar and its parental isoline to the soil fungal community using
      stable isotope probing (SIP). * The microbes receiving (13)C from the plant were
      assessed through RNA/phospholipid fatty acid analysis with stable isotope probing
      (PLFA-SIP) at three time-points (1, 5 and 12 d after the start of labeling). The
      communities of Ascomycota, Basidiomycota and Glomeromycota were analysed
      separately with RT-qPCR and terminal restriction fragment length polymorphism (T
      RFLP). * Ascomycetes and glomeromycetes received carbon from the plant as early
      as 1 and 5 d after labeling, while basidiomycetes were slower in accumulating the
      labeled carbon. The rate of carbon allocation in the GM variety differed from
      that in its parental variety, thereby affecting soil fungal communities. * We
      conclude that both saprotrophic and mycorrhizal fungi rapidly metabolize organic
      substrates flowing from the root into the rhizosphere, that there are large
      differences in utilization of root-derived compounds at a lower phylogenetic
      level within investigated fungal phyla, and that active communities in the
      rhizosphere differ between the GM plant and its parental cultivar through effects
      of differential carbon flow from the plant.

PMID- 22413849
TI  - Tunable helical assemblies of L-alanine methyl ester-containing
      polyphenylacetylene.
AB  - The self-assemblying behaviors of L-alanine methyl ester-containing
      polyphenylacetylene (PPA-Ala, in Chart 1 ) were investigated upon the evaporation
      of its solvent on mica and on air/water interfaces. The introduction of chiral
      amino acid attachments to the polyphenylacetylene backbone induced a helical
      conformation of the backbone, which was stabilized by various noncovalent
      interactions, especially hydrophobic effect and hydrogen bonds. The helicity of
      the polymer was further amplified in its higher-order self-assemblies as the
      formation of helical fibers on the surface of mica upon natural evaporation of
      its THF solution. By LB technique, the polymer chains were guided to form ordered
      parallel ridges and highly aligned, with their helical conformation still
      remaining. The reorganization of the chiral polymer chains on air/water interface
      was associated with the additional hydrophobic effect of PPA-Ala on an air/water
      interface. The polymer backbones had to adopt different arrangements to minimize
      their contact with water, and this adjustment led to the formation of aligned
      polymer ridges under proper surface pressure.

PMID- 22413850
TI  - Assessing the validity of an ELISA test for the serological diagnosis of human
      fascioliasis in different epidemiological situations.
AB  - OBJECTIVES: To improve the diagnosis of human fascioliasis caused by Fasciola
      hepatica and Fasciola gigantica, we evaluated the diagnostic accuracy of an
      enzyme-linked immunosorbent assay (ELISA), with Fasciola antigen from the adult
      liver fluke, for the detection of IgG against fascioliasis in human sera.
      METHODS: The sera of 54 fascioliasis cases, originating from three endemic areas,
      were used in this evaluation: (i) a hyperendemic F. hepatica area where humans
      usually shed a great number of parasite eggs in faeces (11 sera); (ii) an
      epidemic F. hepatica area where humans usually shed small amounts of parasite
      eggs (24 sera) and (iii) an overlap area of both Fasciola species and where human
      shedding of parasite eggs in faeces is usually scarce or non-existent (19 sera).
      One hundred and sixty-eight patients with other parasitic infections and 89
      healthy controls were also analysed. RESULTS: The respective sensitivity and
      specificity of this assay were 95.3% (95% confidence intervals, 82.9-99.2%) and
      95.7% (95% confidence intervals, 92.3-97.5%). No correlation between egg output
      and the OD450 values of the F. hepatica IgG ELISA test was observed. CONCLUSIONS:
      This test could be used both as an individual serodiagnostic test for human
      fascioliasis when backed up by a compatible clinical history together with a
      second diagnostic technique for other cross-reactive helminth infections, and in
      large-scale epidemiological studies of human fascioliasis worldwide.

PMID- 22413851
TI  - Dietary intake and stress fractures among elite male combat recruits.
AB  - BACKGROUND: Appropriate and sufficient dietary intake is one of the main
      requirements for maintaining fitness and health. Inadequate energy intake may
      have a negative impact on physical performance which may result in injuries among
      physically active populations. The purpose of this research was to evaluate a
      possible relationship between dietary intake and stress fracture occurrence among
      combat recruits during basic training (BT). METHODS: Data was collected from 74
      combat recruits (18.2 +/- 0.6 yrs) in the Israeli Defense Forces. Data analyses
      included changes in anthropometric measures, dietary intake, blood iron and
      calcium levels. Measurements were taken on entry to 4-month BT and at the end of
      BT. The occurrence of stress reaction injury was followed prospectively during
      the entire 6-month training period. RESULTS: Twelve recruits were diagnosed with
      stress fracture in the tibia or femur (SF group). Sixty two recruits completed BT
      without stress fractures (NSF). Calcium and vitamin D intakes reported on
      induction day were lower in the SF group compared to the NSF group-38.9% for
      calcium (589 +/- 92 and 964 +/- 373 mg.d-1, respectively, p < 0.001), and-25.1%
      for vitamin D (117.9 +/- 34.3 and 157.4 +/- 93.3 IU.d-1, respectively, p <
      0.001). During BT calcium and vitamin D intake continued to be at the same low
      values for the SF group but decreased for the NSF group and no significant
      differences were found between these two groups. CONCLUSIONS: The development of
      stress fractures in young recruits during combat BT was associated with dietary
      deficiency before induction and during BT of mainly vitamin D and calcium. For
      the purpose of intervention, the fact that the main deficiency is before
      induction will need special consideration.

PMID- 22413852
TI  - Oxidative stress in inflammation-based gastrointestinal tract diseases:
      challenges and opportunities.
AB  - Oxygen free radicals in excessively high amounts are all very reactive chemically
      and can impose a detrimental influence on living organisms by provoking
      "oxidative stress" that can damage major cellular constituents. The latter
      includes the cell membrane, cytoplasmic proteins, and nuclear DNA. Conversely,
      nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS)
      when present in low amounts play an important role as regulatory mediators in
      signaling processes, through which, paradoxically, many ROS-mediated responses
      can protect the cells against oxidative stress by induction of "redox
      homeostasis." Therefore, diseases associated with free radical overproduction are
      provoked by "blazed ROS productions" far beyond the host's capacity to quench.
      Free radicals have been implicated in the pathogenesis of diverse
      gastrointestinal (GI) diseases including gastroesophageal reflux disease (GERD),
      gastritis, enteritis, colitis and associated cancers as well as pancreatitis and
      liver cirrhosis. This article provides an overview of the role of oxidative
      stress in inflammation-based GI tract diseases, including reflux esophagitis,
      Helicobacter pylori-associated gastritis, non-steroidal anti-inflammatory drug
      induced enteritis, ulcerative colitis, and associated colorectal cancer. The
      challenging issue that ROS can contribute to diverse gastrointestinal
      dysfunction, or manifest dual roles in cancer promotion or cancer suppression
      will also be discussed for the opportunity to enhance understanding of
      inflammation-based GI diseases.

PMID- 22413853
TI  - Tolerance within the sleeve inserts of different surgical guides for guided
      implant surgery.
AB  - OBJECTIVES: Recently, guided implant surgery has been introduced and several
      studies verified its accuracy. While those studies reported on the accuracy of
      the entire procedure, this experiment wanted to evaluate the degree of deviation
      that can occur during the drilling procedure alone, due to the tolerance of the
      drill in the sleeve insert. MATERIAL AND METHODS: Drilling was executed in a
      plexi-glass box with a maximal inclination of the drills within the sleeve
      insert. Different sleeve inserts, sleeve positions, sleeve heights, sleeve insert
      heights and diameters were evaluated. RESULTS: The two tested sleeve inserts gave
      a maximum deviation in angulation of 5.2 degrees  and a maximum horizontal
      deviation of 1.3 mm at the implant shoulder and 2.4 mm at the apex for a 13 mm
      implant. These deviations decreased if the distance of the sleeve above the plexi
      glass box became smaller and hand hold sleeve inserts gave less deviation than
      drill hold sleeve inserts. The deviation increased by longer implant length,
      larger drill key diameter, shorter sleeves and/or drill key heights. CONCLUSIONS:
      For a minimal deviation during the surgery with a stereolithographic guide, it is
      very important to use the drill in a centric position, parallel to the cylinder.
      The use of longer drill keys and sleeves are critical for optimal accuracy.

PMID- 22413854
TI  - Simultaneous measurement of urinary albumin and total protein may facilitate
      decision-making in HIV-infected patients with proteinuria.
AB  - OBJECTIVE: We recently showed that a urine albumin/total protein ratio (uAPR)
      <0.4 identifies tubular pathology in proteinuric patients. In tubular disorders,
      proteinuria is usually of low molecular weight and contains relatively little
      albumin. We tested the hypothesis that uAPR is useful in identifying tubular
      pathology related to antiretroviral use in HIV-infected patients. METHODS: We
      retrospectively identified urine protein/creatinine ratios (uPCRs) in HIV
      infected patients. A subset of samples had uPCR and urine albumin/creatinie ratio
      (uACR) measured simultaneously. We classified proteinuric patients (uPCR >30
      mg/mmol) into two groups: those with predominantly 'tubular' proteinuria (TP)
      (uAPR <0.4) and those with predominantly 'glomerular' proteinuria (GP) (uAPR >=
      0.4). RESULTS: A total of 618 of 5244 samples from 1378 patients had uPCR >= 30
      mg/mmol. uAPRs were available in 144 patients: 46 patients (32%) had TP and 21
      (15%) GP; the remainder had uPCR <30 mg/mmol. The TP group had a higher
      fractional excretion of phosphate compared with the GP group (mean 27% vs. 16%,
      respectively; P<0.01). Patients with TP were more likely to be on tenofovir
      and/or a boosted protease inhibitor compared with those with GP. In 18 patients
      with heavy proteinuria (uPCR >100 mg/mmol), a renal assessment was made; eight
      had a kidney biopsy. In all cases, the uAPR results correlated with the
      nephrological diagnosis. CONCLUSIONS: In HIV-infected patients, measuring uAPR
      may help to identify patients in whom a renal biopsy is indicated, and those in
      whom tubular dysfunction might be an important cause of proteinuria and which may
      be related to antiretroviral toxicity. We suggest that this would be useful as a
      routine screening procedure in patients with proteinuria.

PMID- 22413855
TI  - MDM2 SNP309T>G polymorphism increases susceptibility to hepatitis B virus-related
      hepatocellular carcinoma in a northeast Han Chinese population.
AB  - BACKGROUND AND AIMS: The murine double minute 2 (MDM2) gene encodes a negative
      regulator of the tumour protein p53. A single nucleotide polymorphism (SNP) in
      MDM2 promoter, SNP309 T > G, has been showed to influence MDM2 protein expression
      and accelerate tumour formation. To investigate further the role of this locus,
      we examined the association of the SNP with hepatitis B virus (HBV)-related
      hepatocellular carcinoma (HCC) in a northeast Han Chinese population. METHODS:
      MDM2 SNP309 was genotyped in 310 HBV-related HCC patients, 314 non-HCC subjects
      with HBV infection and 480 healthy controls by using a PCR-RFLP method. RESULTS:
      Significant differences of MDM2 SNP309 were detected between HBV-related HCC
      patients and healthy controls (OR 1.729, 95%CI 1.369-2.183, P < 0.0001) or non
      HCC subjects with HBV infection (OR 1.351, 95% CI 1.060-1.722, P = 0.015) by a
      logistic regression analysis. Our data also revealed that subjects with the G
      allele had higher HBV-related HCC susceptibility than those with the T allele in
      various genetic models. In a meta-analysis, where we pooled our data with other
      published studies, the association between this loci and the disease was further
      confirmed (pooled OR 1.54, 95% CI 1.37-1.72, P < 0.0001). CONCLUSIONS: These
      results suggested that the MDM2 SNP309 might influence the risk of developing HBV
      related HCC in a northeast Han Chinese population.

PMID- 22413856
TI  - B-mode and colour Doppler sonographic examination of the milk vein and
      musculophrenic vein in dry cows and cows with a milk yield of 10 and 20 kg.
AB  - BACKGROUND: This study investigated the effect of milk yield on blood flow
      variables in the milk vein and musculophrenic vein in dairy cows. METHODS: Five
      healthy dry cows, five cows with a daily milk yield of 10 kg and five others with
      a daily milk yield of 20 kg underwent B-mode and colour Doppler sonographic
      examination. The diameter of the veins, blood flow velocities and blood flow
      volumes were measured on both sides in standing, non-sedated cows using a 7.5 MHz
      linear transducer. RESULTS: Lactating cows had significantly higher blood flow
      velocities in the milk vein than dry cows; the maximum blood flow velocity of dry
      cows and those with a daily milk yield of 10 and 20 kg were 14.04, 38.77 and
      39.49 cm/s, respectively, the minimum velocities were 0.63, 3.02 and 2.64 cm/s,
      respectively, and the mean maximum velocities were 8.21, 26.67 und 28.22 cm/s,
      respectively. Cows producing 20 kg of milk a day had a blood flow volume of 3.09
      l/min, which was significantly higher than 0.79 l/min recorded in dry cows.
      Lactating cows had significantly higher mean maximum blood flow velocities in the
      musculophrenic vein than dry cows. Blood flow variables of both veins did not
      differ significantly between the left and right side. CONCLUSION: This study
      showed that milk yield has a profound effect on blood flow variables in the milk
      vein and to a lesser extent the musculophrenic vein. This must be taken into
      consideration in future Doppler sonographic studies of these veins and possibly
      other vessels. Furthermore, measurements on one side are representative of both
      sides.

PMID- 22413857
TI  - Is myomectomy always the best choice for infertile women with symptomatic uterine
      fibroids?
AB  - Uterine artery embolization (UAE) is still regarded by most gynaecologists as
      contraindicated for women with symptomatic fibroids and otherwise unexplained
      infertility. For such patients, myomectomy is the usual option. We performed UAE
      as treatment of menorrhagia in an infertile woman with multiple subserosal and
      intramural fibroids who had previously failed multiple myomectomy. UAE resulted
      in durable symptom relief and substantial reduction of the uterine and fibroid
      size. The patient conceived spontaneously 20 months after UAE and progressed
      through pregnancy uneventfully. At 38 weeks of gestation, she underwent elective
      cesarean section and delivered a normal, healthy, 3180-g fetus without
      complications. The present case demonstrates that in symptomatic women with
      multiple subserosal and intramural fibroids and otherwise unexplained
      infertility, UAE may have symptomatic and reproductive outcomes superior to those
      of myomectomy.

PMID- 22413858
TI  - Effects of point substitutions on the structure of toxic Alzheimer's beta-amyloid
      channels: atomic force microscopy and molecular dynamics simulations.
AB  - Alzheimer's disease (AD) is a misfolded protein disease characterized by the
      accumulation of beta-amyloid (Abeta) peptide as senile plaques, progressive
      neurodegeneration, and memory loss. Recent evidence suggests that AD pathology is
      linked to the destabilization of cellular ionic homeostasis mediated by toxic
      pores made of Abeta peptides. Understanding the exact nature by which these pores
      conduct electrical and molecular signals could aid in identifying potential
      therapeutic targets for the prevention and treatment of AD. Here using atomic
      force microscopy (AFM) and molecular dynamics (MD) simulations, we compared the
      imaged pore structures with models to predict channel conformations as a function
      of amino acid sequence. Site-specific amino acid (AA) substitutions in the wild
      type Abeta(1-42) peptide yield information regarding the location and
      significance of individual AA residues to its characteristic structure-activity
      relationship. We selected two AAs that our MD simulation predicted to inhibit or
      permit pore conductance. The substitution of Phe19 with Pro has previously been
      shown to eliminate conductance in the planar lipid bilayer system. Our MD
      simulations predict a channel-like shape with a collapsed pore, which is
      supported by the AFM channel images. We suggest that proline, a known beta-sheet
      breaker, creates a kink in the center of the pore and prevents conductance via
      blockage. This residue may be a viable target for drug development studies aiming
      to inhibit Abeta from inducing ionic destabilization toxicity. The substitution
      of Phe20 with Cys exhibits pore structures indistinguishable from the wild type
      in AFM images. MD simulations predict site 20 to face the solvated pore. Overall,
      the mutations support the previously predicted beta-sheet-based channel
      structure.

PMID- 22413861
TI  - Stabilization of graphene sheets by a structured benzene/hexafluorobenzene mixed
      solvent.
AB  - Applications requiring pristine graphene derived from graphite demand a solution
      stabilization method that utilizes an easily removable media. Using a combination
      of molecular dynamics simulations and experimental techniques, we investigate the
      solublization/suspension of pristine graphene sheets by an equimolar mixture of
      benzene and hexafluorobenzene (C(6)H(6)/C(6)F(6)) that is known to form an
      ordered structure solidifying at 23.7  degrees C. Our simulations show that the
      graphene surface templates the self-assembly of the mixture into periodic layers
      extending up to 30 A from both sides of the graphene sheet. The solvent
      structuring is driven by quadrupolar interactions and consists of stacks of
      alternating C(6)H(6)/C(6)F(6) molecules rising from the surface of the graphene.
      These stacks result in density oscillations with a period of about 3.4 A. The
      high affinity of the 1:1 C(6)H(6)/C(6)F(6) mixture with graphene is consistent
      with observed hysteresis in Wilhelmy plate measurements using highly ordered
      pyrolytic graphite (HOPG). AFM, SEM, and TEM techniques verify the state of the
      suspended material after sonication. As an example of the utility of this
      mixture, graphene suspensions are freeze-dried at room temperature to produce a
      sponge-like morphology that reflects the structure of the graphene sheets in
      solution.

PMID- 22413859
TI  - Anticancer beta-hairpin peptides: membrane-induced folding triggers activity.
AB  - Several cationic antimicrobial peptides (AMPs) have recently been shown to
      display anticancer activity via a mechanism that usually entails the disruption
      of cancer cell membranes. In this work, we designed an 18-residue anticancer
      peptide, SVS-1, whose mechanism of action is designed to take advantage of the
      aberrant lipid composition presented on the outer leaflet of cancer cell
      membranes, which makes the surface of these cells electronegative relative to the
      surface of noncancerous cells. SVS-1 is designed to remain unfolded and inactive
      in aqueous solution but to preferentially fold at the surface of cancer cells,
      adopting an amphiphilic beta-hairpin structure capable of membrane disruption.
      Membrane-induced folding is driven by electrostatic interaction between the
      peptide and the negatively charged membrane surface of cancer cells. SVS-1 is
      active against a variety of cancer cell lines such as A549 (lung carcinoma), KB
      (epidermal carcinoma), MCF-7 (breast carcinoma), and MDA-MB-436 (breast
      carcinoma). However, the cytotoxicity toward noncancerous cells having typical
      membrane compositions, such as HUVEC and erythrocytes, is low. CD spectroscopy,
      appropriately designed peptide controls, cell-based studies, liposome leakage
      assays, and electron microscopy support the intended mechanism of action, which
      leads to preferential killing of cancerous cells.

PMID- 22413862
TI  - Large-scale functional RNAi screen in C. elegans identifies genes that regulate
      the dysfunction of mutant polyglutamine neurons.
AB  - BACKGROUND: A central goal in Huntington's disease (HD) research is to identify
      and prioritize candidate targets for neuroprotective intervention, which requires
      genome-scale information on the modifiers of early-stage neuron injury in HD.
      RESULTS: Here, we performed a large-scale RNA interference screen in C. elegans
      strains that express N-terminal huntingtin (htt) in touch receptor neurons. These
      neurons control the response to light touch. Their function is strongly impaired
      by expanded polyglutamines (128Q) as shown by the nearly complete loss of touch
      response in adult animals, providing an in vivo model in which to manipulate the
      early phases of expanded-polyQ neurotoxicity. In total, 6034 genes were examined,
      revealing 662 gene inactivations that either reduce or aggravate defective touch
      response in 128Q animals. Several genes were previously implicated in HD or
      neurodegenerative disease, suggesting that this screen has effectively identified
      candidate targets for HD. Network-based analysis emphasized a subset of high
      confidence modifier genes in pathways of interest in HD including metabolic,
      neurodevelopmental and pro-survival pathways. Finally, 49 modifiers of 128Q
      neuron dysfunction that are dysregulated in the striatum of either R/2 or CHL2 HD
      mice, or both, were identified. CONCLUSIONS: Collectively, these results
      highlight the relevance to HD pathogenesis, providing novel information on the
      potential therapeutic targets for neuroprotection in HD.

PMID- 22413864
TI  - Cyclooxygenase-2 inhibition restores ultraviolet B-induced downregulation of
      ATP2A2/SERCA2 in keratinocytes: possible therapeutic approach of cyclooxygenase-2
      inhibition for treatment of Darier disease.
AB  - BACKGROUND:   ATP2A2 encoding the sarcoplasmic/endoplasmic reticulum Ca(2+) 
      ATPase2 (SERCA2) is a Darier disease (DD)-related gene. Ultraviolet (UV) B
      irradiation downregulates ATP2A2/SERCA2 expression in keratinocytes, whereas
      cyclooxygenase-2 (COX-2) expression is dramatically upregulated by UVB.
      OBJECTIVES:  To analyse the involvement of COX-2 in ATP2A2/SERCA2 expression.
      METHODS:   Keratinocytes were transfected with COX-2 siRNA or treated with COX-2
      inhibitor, celecoxib, to evaluate the effect of COX-2 on ATP2A2/SERCA2
      expression. Quantitative real-time polymerase chain reaction, Western blotting
      analysis and reporter assay were used to determine the amount of mRNA, protein
      level and transcription activity, respectively. RESULTS:   COX-2 knockdown by
      siRNA resulted in upregulation of ATP2A2 transcription. Treatment by celecoxib
      rescued UVB-mediated suppression of the ATP2A2 transcription and SERCA2 protein
      expression. Simple addition of prostaglandin (PG) E(2) , which is a product of
      COX-2 enzyme, reduced the amounts of ATP2A2 mRNA and SERCA2 protein in
      keratinocytes. CONCLUSIONS:   UVB downregulates ATP2A2/SERCA2 expression via
      induction of COX-2 expression and subsequent increase of PGE(2) production in
      keratinocytes. Considering that DD is caused by the decreased function of SERCA2
      due to the reduced expression of the ATP2A2 gene, this finding shows the
      possibility that COX-2 inhibition may be useful to prevent and/or treat DD.

PMID- 22413865
TI  - Is there a world beyond bevacizumab in targeting angiogenesis in glioblastoma?
AB  - INTRODUCTION: Antiangiogenic approaches are currently the dominating experimental
      therapeutic strategy in glioblastoma. First enthusiasm was provoked by promising
      radiological response rates and an apparent clinical benefit with some of these
      agents. Major limitations include the modest number of durable responses, the
      lack of cytotoxic antitumor activity, of synergy when combined with chemotherapy
      and of an overall survival benefit. AREAS COVERED: We review the rationale as
      well as preclinical and clinical evidence for the future development of
      antiangiogenic agents in glioblastoma. The most prominent approach targets VEGF
      and includes agents such as the VEGF antibody bevacizumab, the VEGF receptor
      fusion protein aflibercept or the tyrosine kinase inhibitors cediranib and XL
      184. Inhibition of angiogenic pathways by small molecules, for example,
      enzastaurin, or anti-integrin-based approaches, for example, cilengitide,
      represent alternative strategies. EXPERT OPINION: Enzastaurin and cediranib
      failed in randomized Phase III trials in recurrent glioblastoma, aflibercept in
      Phase II. By contrast, bevacizumab was conditionally approved in many countries.
      Recently completed Phase III trials for bevacizumab and cilengitide in the first
      line setting will define the future role of these agents. This intense clinical
      trial activity reflects the hope that antiangiogenic agents will become part of
      the limited therapeutic options for glioblastoma.

PMID- 22413863
TI  - Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP)
      proteins and clinical candidate for the treatment of cancer (GDC-0152).
AB  - A series of compounds were designed and synthesized as antagonists of cIAP1/2, ML
      IAP, and XIAP based on the N-terminus, AVPI, of mature Smac. Compound 1 (GDC
      0152) has the best profile of these compounds; it binds to the XIAP BIR3 domain,
      the BIR domain of ML-IAP, and the BIR3 domains of cIAP1 and cIAP2 with K(i)
      values of 28, 14, 17, and 43 nM, respectively. These compounds promote
      degradation of cIAP1, induce activation of caspase-3/7, and lead to decreased
      viability of breast cancer cells without affecting normal mammary epithelial
      cells. Compound 1 inhibits tumor growth when dosed orally in the MDA-MB-231
      breast cancer xenograft model. Compound 1 was advanced to human clinical trials,
      and it exhibited linear pharmacokinetics over the dose range (0.049 to 1.48
      mg/kg) tested. Mean plasma clearance in humans was 9 +/- 3 mL/min/kg, and the
      volume of distribution was 0.6 +/- 0.2 L/kg.

PMID- 22413866
TI  - Amphiphilic phosphoprotein-controlled formation of amorphous calcium carbonate
      with hierarchical superstructure.
AB  - Amorphous calcium carbonate (ACC) plays important roles in biomineralization, and
      the phosphoproteins extracted from biogenic stable ACC can induce and stabilize
      synthetic ACC in vitro. Here, mineralization of square-shaped ACC plates with
      micrometer-sized channels has been reported in the presence of the amphiphilic
      phosphoprotein casein. Casein can be assumed to take a key role during ACC plate
      formation, where it serves as an effective stabilization agent for ACC and
      assembles spherical ACC particles into ACC plates. The stabilizing effect of
      casein arises from the electrostatic attraction between phosphate groups as well
      as carbonate groups (especially the former) and the calcium ions, preventing the
      transformation from unstable ACC to the more stable crystalline phase of CaCO(3).
      The assembling effect of casein mainly comes from the hydrophobic interaction
      between casein molecules bound on CaCO(3) particle surface. The inclusion of
      casein in ACC plates revealed by the thermogavimetric analysis confirms the
      proposed stabilizing and assembling mechanism. The ability to fabricate such
      novel hierarchical structured ACC holds the promise for creating more complex
      micro- and nanostructured materials by use of biological proteins with special
      structure.

PMID- 22413867
TI  - The evolution of reproductive structures in seed plants: a re-examination based
      on insights from developmental genetics.
AB  - The study of developmental genetics is providing insights into how plant
      morphology can and does evolve, and into the fundamental nature of specific
      organs. This new understanding has the potential to revise significantly the way
      we think about seed plant evolution, especially with regard to reproductive
      structures. Here, we have sought to take a step in bridging the divide between
      genetic data and critical fields such as paleobotany and systematics. We discuss
      the evidence for several evolutionarily important interpretations, including the
      possibility that ovules represent meristematic axes with their own type of
      lateral determinate organs (integuments) and a model that considers carpels as
      analogs of complex leaves. In addition, we highlight the aspects of reproductive
      development that are likely to be highly labile and homoplastic, factors that
      have major implications for the understanding of seed plant relationships.
      Although these hypotheses may suggest that some long-standing interpretations are
      misleading, they also open up whole new avenues for comparative study and suggest
      concrete best practices for evolutionary analyses of development.

PMID- 22413868
TI  - A rare lethal case of chondrodysplasia punctata with extensive airway
      involvement.
AB  - Stippled cartilaginous calcification, an important radiologic sign, is described
      as ''chondrodysplasia punctata'' when seen in association with limb shortening
      and maxillofacial hypoplasia. We report chondrodysplasia punctata in a male
      neonate who presented with limb shortening, midfacial hypoplasia, and laryngeal
      stenosis leading to death within a few minutes of birth. A post-mortem radiograph
      revealed generalized punctate calcification of cartilaginous structures,
      including airways, rib ends, spine, long bone epiphyses, tarsus and pinna, and
      brachytelephalangy.

PMID- 22413869
TI  - Insufficient maintenance DNA methylation is associated with abnormal embryonic
      development.
AB  - BACKGROUND: Early pregnancy loss (EPL) is a frustrating clinical problem, whose
      mechanisms are not completely understood. DNA methylation, which includes
      maintenance methylation and de novo methylation directed by DNA
      methyltransferases (DNMTs), is important for embryo development. Abnormal
      function of these DNMTs may have serious consequences for embryonic development.
      METHODS: To evaluate the possible involvement of DNA methylation in human EPL,
      the expression of DNMT proteins and global methylation of DNA were assessed in
      villous or decidua from EPL patients. The association of maintenance methylation
      with embryo implantation and development was also examined. RESULTS: We found
      that DNMT1 and DNMT3A were both expressed in normal human villous and decidua.
      DNMT1 expression and DNA global methylation levels were significantly down
      regulated in villous of EPL. DNMT3A expression was not significantly changed in
      the EPL group compared to controls in either villous or decidua. We also found
      that disturbance of maintenance methylation with a DNMT1 inhibitor may result in
      a decreased global DNA methylation level and impaired embryonic development in
      the mouse model, and inhibit in vitro embryo attachment to endometrial cells.
      CONCLUSIONS: Our results demonstrate that defects in DNA maintenance methylation
      in the embryo, not in the mother, are associated with abnormal embryonic
      implantation and development. The findings of the current study provide new
      insights into the etiology of EPL.

PMID- 22413870
TI  - Caudal anaesthesia of the infraorbital nerve for diagnosis of idiopathic
      headshaking and caudal compression of the infraorbital nerve for its treatment,
      in 58 horses.
AB  - REASONS FOR PERFORMING STUDY: Idiopathic headshaking is often a facial pain
      syndrome, but a diagnostic protocol has not been described. In a previous study,
      caudal compression of the infraorbital nerve for treatment offered a fair success
      rate, but low case numbers and short follow-up time were limitations. OBJECTIVES:
      To describe a diagnostic protocol for headshaking, examining the role of
      bilateral local analgesia of the posterior ethmoidal nerve (PET block). To report
      longer-term follow-up after surgery of the original cases and further cases and
      to determine whether changes to the technique influence success rates and
      complications. METHODS: Records of horses that had undergone PET block and caudal
      compression surgery at 3 hospitals were reviewed. Modifications to the surgical
      technique included placing additional coils into the infraorbital canal and/or
      performing concurrent laser cautery of the nerve. Follow-up information was
      obtained by telephone contact with owners. RESULTS: The PET block was performed
      in 27 horses, with a positive result in 23 of 27 (85%). Surgery was performed in
      58 horses. A successful outcome was initially achieved in 35 of 57 (63%) horses,
      but recurrence occurred between 9 and 30 months later in 9 (26%). Surgery was
      repeated in 10 of 31 (32%) horses. Final success rate, considering only response
      to the last performed surgery, was 28 of 57 (49%) horses with median follow-up
      time of 18 months (range 2-66 months). Nose-rubbing was reported post operatively
      in 30 of 48 (63%) horses. This resolved in all but 4 horses, which were subjected
      to euthanasia. Response to PET block or change in surgical technique did not
      appear to influence outcome or complications. CONCLUSIONS AND POTENTIAL
      RELEVANCE: The diagnostic protocol described is recommended for the investigation
      of headshakers. Caudal compression offers the best prognosis for a successful
      outcome compared with other treatments, for horses in which the only alternative
      is euthanasia. Surgical treatment of the disorder requires refinement, and the
      pathogenesis of the disorder requires investigation.

PMID- 22413871
TI  - M cell targeting by a Claudin 4 targeting peptide can enhance mucosal IgA
      responses.
AB  - BACKGROUND: Mucosal immune surveillance is thought to be largely achieved through
      uptake by specialized epithelial M cells. We recently identified Claudin 4 as an
      M cell target receptor and developed a Claudin 4 targeting peptide (CPE) that can
      mediate uptake of nanoparticles through Nasal Associated Lymphoid Tissue (NALT) M
      cells. METHODS: Recombinant influenza hemagglutinin (HA) and a version with the
      CPE peptide at the C-terminal end was used to immunize mice by the intranasal
      route along with a single dose of cholera toxin as an adjuvant. Serum and mucosal
      IgG and IgA responses were tested for reactivity to HA. RESULTS: We found that
      the recombinant HA was immunogenic on intranasal administration, and inclusion of
      the CPE targeting peptide induced higher mucosal IgA responses. This mucosal
      administration also induced systemic serum IgG responses with Th2 skewing, but
      targeting did not enhance IgG responses, suggesting that the IgG response to
      mucosal immunization is independent of the effects of CPE M cell targeting.
      CONCLUSIONS: M cell targeting mediated by a Claudin 4-specific targeting peptide
      can enhance mucosal IgA responses above the response to non-targeted mucosal
      antigen. Since Claudin 4 has also been found to be regulated in human Peyer's
      patch M cells, the CPE targeting peptide could be a reasonable platform delivery
      technology for mucosal vaccination.

PMID- 22413872
TI  - Pathogenesis and management of pruritus in cholestatic liver disease.
AB  - Patients with cholestatic liver diseases such as primary biliary cirrhosis,
      primary sclerosing cholangitis and intrahepatic cholestasis of pregnancy commonly
      complain of pruritus. The underlying pathogenesis remains obscure with several
      mediators possibly playing an important role; these include lysophosphatidic
      acid, bile salts, opioids, histamine and progesterone metabolites. We describe in
      this review novel insights into the pathogenesis and management of pruritus in
      patients with cholestasis.

PMID- 22413873
TI  - Effect of microthread presence and restoration design (screw versus cemented) in
      dental implant reliability and failure modes.
AB  - OBJECTIVES: This study evaluated the reliability and failure modes of implants
      with a microthreaded or smooth design at the crestal region, restored with
      screwed or cemented crowns. The postulated null hypothesis was that the presence
      of microthreads in the implant cervical region would not result in different
      reliability and strength to failure than smooth design, regardless of fixation
      method, when subjected to step-stress accelerated life-testing (SSALT) in water.
      MATERIALS AND METHODS: Eighty four dental implants (3.3 * 10 mm) were divided
      into four groups (n = 21) according to implant macrogeometric design at the
      crestal region and crown fixation method: Microthreads Screwed (MS); Smooth
      Screwed (SS); Microthreads Cemented (MC), and Smooth Cemented (SC). The abutments
      were torqued to the implants and standardized maxillary central incisor metallic
      crowns were cemented (MC, SC) or screwed (MS, SS) and subjected to SSALT in
      water. The probability of failure versus cycles (90% two-sided confidence
      intervals) was calculated and plotted using a power law relationship for damage
      accumulation. Reliability for a mission of 50,000 cycles at 150 N (90% 2-sided
      confidence intervals) was calculated. Differences between final failure loads
      during fatigue for each group were assessed by Kruskal-Wallis along with
      Benferroni's post hoc tests. Polarized-light and scanning electron microscopes
      were used for failure analyses. RESULTS: The Beta (beta) value (confidence
      interval range) derived from use level probability Weibull calculation of 1.30
      (0.76-2.22), 1.17 (0.70-1.96), 1.12 (0.71-1.76), and 0.52 (0.30-0.89) for groups
      MC, SC, MS, and SS respectively, indicated that fatigue was an accelerating
      factor for all groups, except for SS. The calculated reliability was higher for
      SC (99%) compared to MC (87%). No difference was observed between screwed
      restorations (MS - 29%, SS - 43%). Failure involved abutment screw fracture for
      all groups. The cemented groups (MC, SC) presented more abutment and implant
      fractures. Significantly higher load to fracture values were observed for SC and
      MC relative to MS and SS (P < 0.001). CONCLUSION: Since reliability and strength
      to failure was higher for SC than for MC, our postulated null hypothesis was
      rejected.

PMID- 22413874
TI  - The MONET trial: week 144 analysis of the efficacy of darunavir/ritonavir (DRV/r)
      monotherapy versus DRV/r plus two nucleoside reverse transcriptase inhibitors,
      for patients with viral load < 50 HIV-1 RNA copies/mL at baseline.
AB  - BACKGROUND: In the MONotherapy in Europe with Tmc114 (MONET) trial,
      darunavir/ritonavir (DRV/r) monotherapy showed noninferior efficacy vs. two
      nucleoside reverse transcriptase inhibitors (NRTIs) plus DRV/r at the primary 48
      week analysis. The trial was continued to week 144 to assess the durability of
      the results. METHODS: A total of 256 patients with viral load < 50 HIV-1 RNA
      copies/mL on current highly active antiretroviral therapy (HAART) for at least 6
      months switched to DRV/r 800/100 mg once daily, either as monotherapy (n=127) or
      with two NRTIs (n=129). Treatment failure was defined as two consecutive HIV RNA
      levels above 50 copies/mL [time to loss of virological response (TLOVR)] by week
      144, or discontinuation of study drugs. RESULTS: Eighty-one per cent of patients
      were male and 91% were Caucasian, and they had a median baseline CD4 count of 575
      cells/uL. More patients in the DRV/r monotherapy arm had hepatitis C virus
      coinfection at baseline than in the control arm (18% vs. 12%, respectively). By
      week 144, the percentage of patients with HIV RNA < 50 copies/mL [intent to treat
      (ITT), TLOVR, switch=failure method] was 69% vs. 75% in the DRV/r monotherapy and
      triple therapy arms [difference= -5.9%; 95% confidence interval (CI) -16.9%,
      +5.1%]; by a strict ITT analysis (switches not considered failures), the
      percentage of patients with HIV RNA < 50 copies/mL was 84% vs. 83.5%,
      respectively (difference= +0.5%; 95% CI -8.7%, +9.7%). Twenty-one and 13 patients
      had two consecutive HIV RNA results above 50 copies/mL in the DRV/r monotherapy
      arm and triple therapy arm, respectively, of whom 18 of 21 (86%) and 10 of 13
      (77%) had HIV RNA < 50 copies/mL at week 144. CONCLUSIONS: In this study, for
      patients with HIV RNA < 50 copies/mL at baseline, switching to DRV/r monotherapy
      showed noninferior efficacy to DRV/r plus two NRTIs in a strict ITT (switches not
      considered failures) analysis, but not in a TLOVR switch equals failure analysis.

PMID- 22413875
TI  - Capital and operating costs of full-scale fecal sludge management and wastewater
      treatment systems in Dakar, Senegal.
AB  - A financial comparison of a parallel sewer based (SB) system with activated
      sludge, and a fecal sludge management (FSM) system with onsite septic tanks,
      collection and transport (C&T) trucks, and drying beds was conducted. The
      annualized capital for the SB ($42.66 capita(-1) year(-1)) was ten times higher
      than the FSM ($4.05 capita(-1) year(-1)), the annual operating cost for the SB
      ($11.98 capita(-1) year(-1)) was 1.5 times higher than the FSM ($7.58 capita(-1)
      year(-1)), and the combined capital and operating for the SB ($54.64 capita(-1)
      year(-1)) was five times higher than FSM ($11.63 capita(-1) year(-1)). In Dakar,
      costs for SB are almost entirely borne by the sanitation utility, with only 6% of
      the annualized cost borne by users of the system. In addition to costing less
      overall, FSM operates with a different business model, with costs spread among
      households, private companies, and the utility. Hence, SB was 40 times more
      expensive to implement for the utility than FSM. However, the majority of FSM
      costs are borne at the household level and are inequitable. The results of the
      study illustrate that in low-income countries, vast improvements in sanitation
      can be affordable when employing FSM, whereas SB systems are prohibitively
      expensive.

PMID- 22413876
TI  - Crosstalk between transcription factors and microRNAs in human protein
      interaction network.
AB  - BACKGROUND: Gene regulatory networks control the global gene expression and the
      dynamics of protein output in living cells. In multicellular organisms,
      transcription factors and microRNAs are the major families of gene regulators.
      Recent studies have suggested that these two kinds of regulators share similar
      regulatory logics and participate in cooperative activities in the gene
      regulatory network; however, their combinational regulatory effects and
      preferences on the protein interaction network remain unclear. METHODS: In this
      study, we constructed a global human gene regulatory network comprising both
      transcriptional and post-transcriptional regulatory relationships, and integrated
      the protein interactome into this network. We then screened the integrated
      network for four types of regulatory motifs: single-regulation, co-regulation,
      crosstalk, and independent, and investigated their topological properties in the
      protein interaction network. RESULTS: Among the four types of network motifs, the
      crosstalk was found to have the most enriched protein-protein interactions in
      their downstream regulatory targets. The topological properties of these motifs
      also revealed that they target crucial proteins in the protein interaction
      network and may serve important roles of biological functions. CONCLUSIONS:
      Altogether, these results reveal the combinatorial regulatory patterns of
      transcription factors and microRNAs on the protein interactome, and provide
      further evidence to suggest the connection between gene regulatory network and
      protein interaction network.

PMID- 22413879
TI  - Preoperative plasma fibrinogen, platelet count and prognosis in epithelial
      ovarian cancer.
AB  - AIM: The aim of the present study was to investigate the correlation between
      fibrinogen level, platelet count and prognosis in patients with epithelial
      ovarian cancer (EOC). MATERIAL AND METHODS: Preoperative fibrinogen level and
      platelet count in 136 EOC patients and 146 patients with benign ovarian tumor,
      and their associations with clinicopathologic parameters and survival in EOC
      patients, were retrospectively analyzed. RESULTS: The fibrinogen level in EOC was
      higher than that in benign patients (3.95 +/- 1.37 g/L versus 2.88 +/- 0.6 g/L, P
      < 0.001), and 36.0% (49/136) of EOC patients had hyperfibrinogenemia (fibrinogen
      >4.0 g/L). The platelet count in EOC was higher than that in benign patients
      (251.5 +/- 89.4 * 10(9) /L versus 206.7 +/- 49.0 * 10(9) /L P < 0.001), and 7.4%
      (10/136) of EOC patients had thrombocytosis (platelet count >400 * 10(9) /L).
      Hyperfibrinogenemia was associated with International Federation of Gynecologists
      and Obstetricians (FIGO) stage, non-optimal cytoreduction and poor chemo
      response, but not with histologic type and grade, CA-125 level, chemotherapy
      method, and age. EOC patients with advanced disease showed higher rate of
      elevated thrombocyte count than patients with early disease (30.7% versus 8.3%, P
      = 0.002). The rate of thrombocytosis was higher in patients with
      hyperfibrinogenemia than in those with normal fibrinogen (9/10 versus 1/10, P <
      0.001). A significant correlation between platelet count and fibrinogen level was
      observed in EOC patients (P < 0.001). In multivariate analysis, overall survival
      was influenced by tumor stage (P < 0.001), chemotherapy with taxane (P < 0.001)
      and fibrinogen level (P = 0.004), and disease-free survival was only influenced
      by tumor stage (P < 0.001). CONCLUSION: Our findings suggest that
      hyperfibrinogenemia may be a predictor for poor chemo-response and have a
      potential role as independent prognostic factors in EOC patients.

PMID- 22413881
TI  - Left atrial volume index as a predictor of ventricle repolarization abnormalities
      in adult dialyzed patients.
AB  - This study was performed to investigate the relationship between left atrium (LA)
      volume index (LAVI) and left ventricle electrical activity presumably
      repolarization in end-stage renal disease patients. Study group was consisted of
      120 dialyzed patients divided into two subgroups: 57 (age 50.7 +/- 7.1) were on
      continuous ambulatory peritoneal dialysis (CAPD) and 73 (age 51.6 +/- 7.6) were
      hemodialyzed (HD). All patients were undergoing three-dimensional
      vectorcardiographic (VCG) monitoring to assess parameters concerning T vector:
      QRS-T angle, Tel, and Taz. Standard echocardiography was performed to assess:
      LAmax, LAshort, LAlong. LAVI was calculated due to formula: LAVI = (pi/6X [LAmax
      * LAshort * LAlong])/m2. LAVI in HD as well as in CAPD patients was significantly
      higher compared with controls (respectively: 36.29 +/- 10.92; 36.41 +/- 11.06;
      20.64 +/- 6.77 mL/m2). The calculated cutoff value of LAVI was 36.32 mL/m2. In HD
      patients, the strong correlations between LAVI and QRS-T angle and Tel were
      determined (respectively: r = 0.407, P < 0.001 and r = 0.359, P = 0.006).
      Similarly in CAPD group were significant associations between LAVI and QRS-T
      angle and Tel (respectively: r = 0.423, P < 0.001 and r = 0.374, P = 0.004). The
      QRS-T angle, Tel and Taz are independently and markedly associated with LAVI in
      both HD and CAPD patients. LAVI and VCG indices are higher in both HD and CAPD
      patients. Correlation between QRS-T angle and LAVI may reflect unfavorable
      influence on the electrical activity of the heart in dialyzed patients with left
      ventricle diastolic dysfunction. LAVI cutoff value is useful biomarker for
      stratification of ventricle repolarization disturbances in those patients.

PMID- 22413882
TI  - Metabolic, toxicological, and safety considerations for drugs used to treat ADHD.
AB  - INTRODUCTION: Pharmacotherapy is frequently used to treat symptoms of attention
      deficit/hyperactivity disorder (ADHD), the most common neurobehavioral disorder
      of childhood. The typically prescribed agents for ADHD have varying durations of
      effect and degrees of efficacy. The broad range of pharmacological treatments
      available allows for both single and combination therapies for achieving optimal
      therapeutic effects. Metabolic, toxicological, and safety information are
      critical for an informed evaluation of the risk/benefit considerations in
      prescribing practices. AREAS COVERED: This article focuses on the medications
      with current FDA approval for use in the treatment of ADHD in pediatric and adult
      populations. This review covers the stimulants (amphetamine and methylphenidate)
      and non-stimulants (atomoxetine, clonidine extended release, and guanfacine
      extended release) used to treat ADHD and presents an overview of their respective
      metabolic, toxicological, and safety features. A literature search and review of
      the relevant medications were carried out using the PubMed database up to
      November 2011. EXPERT OPINION: New trends in study design based on drug profiles
      include the use of adjuvant therapies and the inclusion of patients with
      comorbidities. The recent expansion of inclusion/exclusion criteria in pediatric
      clinical trials of ADHD allows for a more rigorous analysis of associated
      benefits and risks with the use of adjuvant therapy.

PMID- 22413880
TI  - HIV-1 gp41 transmembrane domain interacts with the fusion peptide: implication in
      lipid mixing and inhibition of virus-cell fusion.
AB  - Fusion of the human immunodeficiency virus (HIV) with target cells is mediated by
      the gp41 subunit of the envelope protein. Mutation and deletion studies within
      the transmembrane domain (TMD) of intact gp41 influenced its fusion activity. In
      addition, current models suggest that the TMD is in proximity with the fusion
      peptide (FP) at the late fusion stages, but there are no direct experimental data
      to support this hypothesis. Here, we investigated the TMD focusing on two
      regions: the N-terminal containing the GxxxG motif and the C-terminal containing
      the GLRI motif, which is conserved among the TMDs of HIV and the T-cell receptor.
      Studies utilizing the ToxR expression system combined with synthetic peptides and
      their fluorescent analogues derived from TMD revealed that the GxxxG motif is
      important for TMD self-association, whereas the C-terminal region is for its
      heteroassociation with FP. Functionally, all three TMD peptides induced lipid
      mixing that was enhanced significantly upon mixing with FP. Furthermore, the TMD
      peptides inhibited virus-cell fusion apparently through their interaction with
      their endogenous counterparts. Notably, the R2E mutant (in the GLRI) was
      significantly less potent than the two others. Overall, our findings provide
      experimental evidence that HIV-1 TMD contributes to membrane assembly and
      function of the HIV-1 envelope. Owing to similarities between functional domains
      within viruses, these findings suggest that the TMDs and FPs may contribute
      similarly in other viruses as well.

PMID- 22413883
TI  - Segmental changes in smooth muscle contraction as a predictive factor of the
      response to high-dose proton pump inhibitor treatment in patients with functional
      chest pain.
AB  - BACKGROUND AND AIMS: High-dose proton pump inhibitor (PPI) treatment leads to
      relatively little symptomatic improvement in patients with functional chest pain
      (FCP). This study was to evaluate the use of smooth muscle segmental changes in
      esophageal contraction as measured by topographical plots of high resolution
      manometry (HRM) as predictive factors of the response to high-dose PPI treatment
      in FCP patients. METHODS: Thirty patients diagnosed with FCP were treated with
      rabeprazole 20 mg twice daily for 2 weeks and classified as positive and negative
      responders based on symptom intensity score. HRM topographical plots were
      analyzed for segment lengths, maximal wave amplitudes, and pressure volumes of
      the proximal and distal smooth muscle segments. RESULTS: A positive response was
      observed in 23.3% of the patients. While the pressure volume of the proximal
      segment was significantly higher in the positive responders than the negative
      responders (900.4 +/- 91.5 mm Hg/cm per s vs. 780.5 +/- 133.3 mm Hg/cm per s, P =
      0.017), the pressure volume of the distal segment was significantly lower in the
      positive responders (1914.0 +/- 159.8 mm Hg/cm per s vs. 2140.5 +/- 276.2 mm
      Hg/cm per s, P = 0.014). A prominent shifting in pressure volume to the distal
      segment was observed in the negative responders compared with the positive
      responders (segmental ratio of pressure volume (SRPV): 2.9 +/- 0.5 vs. 2.1 +/-
      0.1, P < 0.001), and 2.39 was found to be the SRPV that best differentiated
      positive and negative responders. CONCLUSIONS: A low SRPV was associated with a
      positive response to high-dose PPI treatment in patients with FCP.

PMID- 22413884
TI  - Explaining regional variations in health care utilization between Swiss cantons
      using panel econometric models.
AB  - BACKGROUND: In spite of a detailed and nation-wide legislation frame, there exist
      large cantonal disparities in consumed quantities of health care services in
      Switzerland. In this study, the most important factors of influence causing these
      regional disparities are determined. The findings can also be productive for
      discussing the containment of health care consumption in other countries.
      METHODS: Based on the literature, relevant factors that cause geographic
      disparities of quantities and costs in western health care systems are
      identified. Using a selected set of these factors, individual panel econometric
      models are calculated to explain the variation of the utilization in each of the
      six largest health care service groups (general practitioners, specialist
      doctors, hospital inpatient, hospital outpatient, medication, and nursing homes)
      in Swiss mandatory health insurance (MHI). The main data source is 'Datenpool
      santesuisse', a database of Swiss health insurers. RESULTS: For all six health
      care service groups, significant factors influencing the utilization frequency
      over time and across cantons are found. A greater supply of service providers
      tends to have strong interrelations with per capita consumption of MHI services.
      On the demand side, older populations and higher population densities represent
      the clearest driving factors. CONCLUSIONS: Strategies to contain consumption and
      costs in health care should include several elements. In the federalist Swiss
      system, the structure of regional health care supply seems to generate
      significant effects. However, the extent of driving factors on the demand side
      (e.g., social deprivation) or financing instruments (e.g., high deductibles)
      should also be considered.

PMID- 22413886
TI  - Sibs with acrocephalopolydactylous dysplasia (Elejalde syndrome) in a non
      consanguineous family.
AB  - Acrocephalopolydactylous dysplasia, (Elejalde syndrome) is a rare condition; only
      six cases have been reported to date. We describe two infants born with Elejalde
      syndrome (ES); compare the clinical, pathological, and histological findings with
      those of known cases of Elejalde syndrome. The post-mortem histology study of the
      skin shows hyperplasia of connective tissues, a diagnostic sign in this
      condition. We describe cardiomegaly, cleft palate, and cryptorchidism not
      reported previously.

PMID- 22413885
TI  - Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and
      Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling.
AB  - BACKGROUND: T lymphocytes are orchestrators of adaptive immunity. Naive T cells
      may differentiate into Th1, Th2, Th17 or iTreg phenotypes, depending on
      environmental co-stimulatory signals. To identify genes and pathways involved in
      differentiation of Jurkat T cells towards Th1 and Th2 subtypes we performed
      comprehensive transcriptome analyses of Jurkat T cells stimulated with various
      stimuli and pathway inhibitors. Results from these experiments were validated in
      a human experimental setting using whole blood and purified CD4+ Tcells. RESULTS:
      Calcium-dependent activation of T cells using CD3/CD28 and PMA/CD3 stimulation
      induced a Th1 expression profile reflected by increased expression of T-bet,
      RUNX3, IL-2, and IFNgamma, whereas calcium-independent activation via PMA/CD28
      induced a Th2 expression profile which included GATA3, RXRA, CCL1 and Itk. Knock
      down with siRNA and gene expression profiling in the presence of selective kinase
      inhibitors showed that proximal kinases Lck and PKCtheta are crucial signaling
      hubs during T helper cell activation, revealing a clear role for Lck in Th1
      development and for PKCtheta in both Th1 and Th2 development. Medial signaling
      via MAPkinases appeared to be less important in these pathways, since specific
      inhibitors of these kinases displayed a minor effect on gene expression.
      Translation towards a primary, whole blood setting and purified human CD4+ T
      cells revealed that PMA/CD3 stimulation induced a more pronounced Th1 specific,
      Lck and PKCtheta dependent IFNgamma production, whereas PMA/CD28 induced Th2
      specific IL-5 and IL-13 production, independent of Lck activation. PMA/CD3
      mediated skewing towards a Th1 phenotype was also reflected in mRNA expression of
      the master transcription factor Tbet, whereas PMA/CD28-mediated stimulation
      enhanced GATA3 mRNA expression in primary human CD4+ Tcells. CONCLUSIONS: This
      study identifies stimulatory pathways and gene expression profiles for in vitro
      skewing of T helper cell activation. PMA/CD3 stimulation enhances a Th1-like
      response in an Lck and PKCtheta dependent fashion, whereas PMA/CD28 stimulation
      results in a Th2-like phenotype independent of the proximal TCR-tyrosine kinase
      Lck. This approach offers a robust and fast translational in vitro system for
      skewed T helper cell responses in Jurkat T cells, primary human CD4+ Tcells and
      in a more complex matrix such as human whole blood.

PMID- 22413887
TI  - Indiosides G-K: steroidal glycosides with cytotoxic and anti-inflammatory
      activities from Solanum violaceum.
AB  - Five new steroidal glycosides (1-5) and nine known compounds were isolated from
      Solanum violaceum. Indiosides G (1) and H (2) are spirostene saponins with an iso
      type F ring, indioside I (3) is a spirostane saponin, and indiosides J (4) and K
      (5) are unusual furostanol saponins with a deformed F ring. These structures
      represent rare naturally occurring steroidal skeletons. The structures of the new
      compounds were elucidated using 1D and 2D spectroscopic techniques and acid
      hydrolysis. Compounds 2, 3, and 7-9 exhibited cytotoxic activity against six
      human cancer cell lines (HepG2, Hep3B, A549, Ca9-22, MDA-MB-231, and MCF-7) with
      IC(50) values of 1.83-8.04 MUg/mL. Steroidal saponins 3, 8, and 9 showed
      inhibitory effects on superoxide anion generation with IC(50) values of 2.84 +/-
      0.18, 0.62 +/- 0.03, and 1.62 +/- 0.59 MUg/mL, respectively. Saponins 8 and 9
      also inhibited elastase release with IC(50) values of 111.05 +/- 7.37 and 4.04 +/
      0.51 MUg/mL, respectively. Structure-activity relationship correlations of these
      compounds with respect to cytotoxic and anti-inflammatory effects are discussed.

PMID- 22413889
TI  - Computer-assisted design/computer-assisted manufacturing zirconia implant fixed
      complete prostheses: clinical results and technical complications up to 4 years
      of function.
AB  - OBJECTIVE: To report the clinical results and technical complications with
      computer-assisted design/computer-assisted manufacturing (CAD/CAM) zirconia,
      implant fixed complete dental prostheses (IFCDPs) after 2-4 years in function.
      MATERIALS AND METHODS: Fourteen consecutive edentulous patients (16 edentulous
      arches) were included in this study. Ten of the patients were women and four were
      men, with an average age of 58 years (range: 35-71). Ten mandibular and six
      maxillary arches were restored with porcelain fused to zirconia (PFZ) IFCDPs. Of
      the 16 arches, 14 received one-piece and 2 received segmented two-piece IFCDPs,
      respectively. The mean clinical follow-up period was 3 years (range: 2-4). At the
      last recall appointment, biological and technical parameters of dental implant
      treatment were evaluated. RESULTS: The implant and prosthesis survival rate
      following prosthesis insertion was 100% up to 4-year follow-up. The prostheses in
      11 of the 16 restored arches were structurally sound, exhibited favorable soft
      tissue response, esthetics, and patient satisfaction. Five IFCDPs (31.25%) in
      four patients exhibited porcelain veneer chipping. Chipping was minor in three
      prostheses (three patients) and was addressed intraorally with polishing (one
      prosthesis) or composite resin (two prostheses). One patient with maxillary and
      mandibular zirconia IFCDP exhibited major porcelain chipping fractures which had
      to be repaired in the laboratory. Function, esthetics, and patient satisfaction
      were not affected in three of the four fracture incidents. Median crestal bone
      loss was 0.1 mm (0.01-0.2 mm). The presence of parafunctional activity, the IFCDP
      as opposing dentition, and the absence of occlusal night guard were associated
      with all the incidents of ceramic chipping. CONCLUSION: CAD/CAM zirconia IFCDPs
      are viable prosthetic treatment after 2-4 years in function, but not without
      complications. The porcelain chipping/fracture was the most frequent technical
      complication, with a 31.25% chipping rate at the prosthesis level. Despite the
      technical complications, increased patient satisfaction was noted.

PMID- 22413890
TI  - The Recent Infection Testing Algorithm (RITA) in clinical practice: a survey of
      HIV clinicians in England and Northern Ireland.
AB  - OBJECTIVES: In order to estimate HIV incidence among high-risk groups, in January
      2009 the Health Protection Agency introduced the Recent Infection Testing
      Algorithm (RITA) in England and Northern Ireland (E&NI), currently the only
      regions to inform patients of RITA results. This survey of HIV specialists aimed
      to investigate the role of RITA in patient management and explore clinicians'
      views on its role in clinical practice and during partner notification. METHODS:
      An online questionnaire was distributed to HIV specialists via the British HIV
      Association membership email list in February 2011. RESULTS: Forty-two HIV
      specialists from 32 HIV centres responded to the survey among 90 centres enrolled
      in the programme (response rate 36%). Testing for recent infection was considered
      standard of care by 83% of respondents, 80% felt confident in interpreting
      results and 92% discussed results with patients, particularly in the context of a
      possible HIV seroconversion illness (96%) or when deciding when to start
      antiretroviral therapy (70%). A third (36%) of specialists were initially
      concerned that RITA results may cause additional anxiety among patients; however,
      no adverse events were reported. The majority (90%) felt that results could
      assist with contact tracing by prioritizing patients with likely recent
      infection. However, only a few centres have currently incorporated RITA into
      their HIV partner notification protocols. CONCLUSIONS: RITA has been introduced
      into clinical practice with no reported patient adverse events. Access to results
      at centre level should be improved. National guidance regarding use of RITA as a
      tool for contact tracing is required.

PMID- 22413888
TI  - Acetate supplementation modulates brain histone acetylation and decreases
      interleukin-1beta expression in a rat model of neuroinflammation.
AB  - BACKGROUND: Long-term acetate supplementation reduces neuroglial activation and
      cholinergic cell loss in a rat model of lipopolysaccharide-induced
      neuroinflammation. Additionally, a single dose of glyceryl triacetate, used to
      induce acetate supplementation, increases histone H3 and H4 acetylation and
      inhibits histone deacetylase activity and histone deacetylase-2 expression in
      normal rat brain. Here, we propose that the therapeutic effect of acetate in
      reducing neuroglial activation is due to a reversal of lipopolysaccharide-induced
      changes in histone acetylation and pro-inflammatory cytokine expression. METHODS:
      In this study, we examined the effect of a 28-day-dosing regimen of glyceryl
      triacetate, to induce acetate supplementation, on brain histone acetylation and
      interleukin-1beta expression in a rat model of lipopolysaccharide-induced
      neuroinflammation. The effect was analyzed using Western blot analysis,
      quantitative real-time polymerase chain reaction and enzymic histone deacetylase
      and histone acetyltransferase assays. Statistical analysis was performed using
      one-way analysis of variance, parametric or nonparametric when appropriate,
      followed by Tukey's or Dunn's post-hoc test, respectively. RESULTS: We found that
      long-term acetate supplementation increased the proportion of brain histone H3
      acetylated at lysine 9 (H3K9), histone H4 acetylated at lysine 8 and histone H4
      acetylated at lysine 16. However, unlike a single dose of glyceryl triacetate,
      long-term treatment increased histone acetyltransferase activity and had no
      effect on histone deacetylase activity, with variable effects on brain histone
      deacetylase class I and II expression. In agreement with this hypothesis,
      neuroinflammation reduced the proportion of brain H3K9 acetylation by 50%, which
      was effectively reversed with acetate supplementation. Further, in rats subjected
      to lipopolysaccharide-induced neuroinflammation, the pro-inflammatory cytokine
      interleukin-1beta protein and mRNA levels were increased by 1.3- and 10-fold,
      respectively, and acetate supplementation reduced this expression to control
      levels. CONCLUSION: Based on these results, we conclude that dietary acetate
      supplementation attenuates neuroglial activation by effectively reducing pro
      inflammatory cytokine expression by a mechanism that may involve a distinct site
      specific pattern of histone acetylation and histone deacetylase expression in the
      brain.

PMID- 22413891
TI  - European outbreaks of atypical myopathy in grazing horses (2006-2009):
      determination of indicators for risk and prognostic factors.
AB  - REASONS FOR PERFORMING STUDY: Appropriate management of atypical myopathy (AM)
      requires the establishment of an accurate diagnosis and prognosis. Furthermore,
      preventive measures to avoid AM need to be refined. OBJECTIVES: The aims of the
      study were as follows: 1) to improve the diagnosis of AM; 2) to identify
      prognostic predictors; and 3) to refine recommended preventive measures based on
      indicators of risk factors. METHODS: An exploratory analysis of cases in Europe
      between 2006 and 2009 reported to the Atypical Myopathy Alert Group was
      conducted. Based on clinical data, reported cases were allocated into 2 groups:
      confirmed or highly probable AM (AM group; further divided into survivors and
      nonsurvivors); and cases with a low probability of having AM or with another
      final diagnosis (non-AM group). Using Welch's test and odds ratios corrected for
      multiple comparisons, the AM vs. non-AM groups were compared to identify
      indicators for diagnosis and risk factors, and survivors vs. nonsurvivors in the
      AM group were compared to identify prognostic factors. Sensitivity, specificity
      and positive and negative predictive values were calculated for specific clinical
      signs related to final diagnosis and outcome. RESULTS: From 600 reported cases,
      354 AM cases (survival rate of 26%) and 69 non-AM cases were identified, while
      there were insufficient data to categorise the remainder. Variables valuable for
      diagnosing AM compared with similar diseases were as follows: presence of dead
      leaves and wood and/or trees on pastures; sloping pastures; full-time pasture
      access; no food supplementation; normal body condition; pigmenturia;
      normothermia; and congested mucous membranes. Nonsurvival was associated with
      recumbency, sweating, anorexia, dyspnoea, tachypnoea and/or tachycardia. Survival
      was associated with remaining standing most of the time, normothermia, normal
      mucous membranes, defaecation and vitamin and antioxidant therapy. CONCLUSIONS
      AND POTENTIAL RELEVANCE: This study refines the list of risk factors for AM.
      Clinical signs valuable for diagnosis and prognosis have been identified,
      enabling clinicians to improve management of AM cases.

PMID- 22413892
TI  - Monophasic synovial sarcoma presenting as a primary ileal mass: a case report and
      review of the literature.
AB  - INTRODUCTION: Synovial sarcoma is a rare malignant mesenchymal tumor mainly
      arising in the peri-articular tissue in young adults. There are few cases
      reported in other areas. CASE PRESENTATION: We report the case of a 29-year-old
      Saudi woman of Arabian ethnicity with synovial sarcoma arising primarily from the
      ileum who presented with abdominal pain, a palpable mass and incomplete
      intestinal obstruction. A literature review was performed to gather information
      on this rare gastrointestinal tract sarcoma. CONCLUSIONS: Although it is a rare
      tumor of the pre-articular tissues, synovial sarcoma can present, in exceedingly
      rare cases, in unusual anatomical sites such as the gastrointestinal tract. We
      believe the reporting of all rare or unexpected presentations of sarcoma will
      eventually improve our understanding of this relatively unusual malignancy.

PMID- 22413893
TI  - VX fate on common matrices: evaporation versus degradation.
AB  - A study of the volatilization rate of the nerve agent VX (O-ethyl S-2-(N,N
      diisopropylamino)ethyl methylphosphonothiolate) from various urban matrices in a
      specially designed climatic chamber (model system) is described. The performance
      of the model system combined with the analytical procedure produced profiles of
      vapor concentration obtained from samples of VX dispersed as small droplets on
      the surfaces of the matrices. The results indicated that the bitumen-containing
      surfaces such as asphalt blocks and bitumen sheets conserve VX and slow-release
      part of it over a long period of time. No complete mass balance could be obtained
      for these surfaces. Influence of environmental and experimental parameters as
      well as the efficacy of decontamination procedure were also measured. From smooth
      surface tiles a fast release of VX was measured and almost a complete mass
      balance was obtained, which characterizes the behavior of inert surfaces.
      Experiments carried out on concrete blocks showed fast decay of the concentration
      profile along with a very poor reconstruction of the initial quantity of VX,
      implying that this matrix degraded VX actively due to its multiple basic
      catalytic sites. To complement this study, solid-state NMR measurements were
      compared to add data concerning agent-fate within the matrices.

PMID- 22413894
TI  - N95 filtering facepiece respirator deadspace temperature and humidity.
AB  - The objective of this study was to determine the levels of heat and humidity that
      develop within the deadspace of N95 filtering facepiece respirators (N95 FFR).
      Seventeen subjects wore two models each of N95 FFR and N95 FFR with an exhalation
      valve (N95 FFR/EV) while exercising on a treadmill at a low-moderate work rate
      for 1 and 2 hr in a temperate ambient environment. FFR deadspace temperature and
      relative humidity were monitored by a wireless sensor housed within the FFR. Each
      FFR was weighed pre- and post-testing to determine moisture retention. After 1
      hr, FFR deadspace temperature and humidity were markedly elevated above ambient
      levels, and the FFR deadspace mean apparent heat index was 54 degrees C. N95
      FFR/EV use resulted in significantly lower deadspace temperatures than N95 FFR (p
      = 0.01), but FFR deadspace humidity levels were not significantly different (p =
      0.32). Compared with the first hour of use, no significant increase in FFR
      deadspace heat and humidity occurred over the second hour. FFR mean moisture
      retention was < 0.3 grams over 2 hr. N95 FFR/EV offer a significant advantage in
      deadspace heat dissipation over N95 FFR at a low-moderate work rate over 1 hr of
      continuous use but offered no additional benefit in humidity amelioration.
      Moisture retention in N95 FFR and N95 FFR/EV is minimal after 2 hr of use.  
      [Supplementary materials are available for this article. Go to the publisher's
      online edition of Journal of Occupational and Environmental Hygiene for the
      following free supplemental resource: a file containing N95 filtering facepiece
      respirator deadspace mean RH and temperature recordings for 17 subjects treadmill
      exercising at 5.6 Km/H over 1 hour.].

PMID- 22413895
TI  - Interchain acetyl transfer in the E2 component of bacterial pyruvate
      dehydrogenase suggests a model with different roles for each chain in a trimer of
      the homooligomeric component.
AB  - The bacterial pyruvate dehydrogenase complex carries out conversion of pyruvate
      to acetyl-coenzyme A with the assistance of thiamin diphosphate (ThDP), several
      other cofactors, and three principal protein components, E1-E3, each present in
      multiple copies. The E2 component forms the core of the complexes, each copy
      consisting of variable numbers of lipoyl domains (LDs, lipoic acid covalently
      amidated at a lysine residue), peripheral subunit binding domains (PSBDs), and
      catalytic (or core) domains (CDs). The reaction starts with a ThDP-dependent
      decarboxylation on E1 to an enamine/C2alpha carbanion, followed by oxidation and
      acetyl transfer to form S-acetyldihydrolipoamide E2, and then transfer of this
      acetyl group from the LD to coenzyme A on the CD. The dihydrolipoamide E2 is
      finally reoxidized by the E3 component. This report investigates whether the
      acetyl group is passed from the LD to the CD in an intra- or interchain reaction.
      Using an Escherichia coli E2 component having a single LD, two types of
      constructs were prepared: one with a Lys to Ala substitution in the LD at the Lys
      carrying the lipoic acid, making E2 incompetent toward post-translational
      ligation of lipoic acid and, hence, toward reductive acetylation, and the other
      in which the His believed to catalyze the transthiolacetylation in the CD is
      substituted with A or C, the absence of His rendering it incompetent toward
      acetyl-CoA formation. Both kinetic evidence and mass spectrometric evidence
      support interchain transfer of the acetyl groups, providing a novel model for the
      presence of multiples of three chains in all E2 components, and their assembly in
      bacterial enzymes.

PMID- 22413896
TI  - Delayed presentation of intraperitoneal bladder rupture following domestic
      violence in pregnancy.
AB  - Trauma during pregnancy can present a unique challenge because of care for the
      mother and the fetus. About 6-7% of all pregnant patients are exposed to some
      sort of trauma, especially during the third trimester, with 0.3-0.4% requiring
      hospitalization. Although mostly accidental, injuries are sometimes caused by
      intentional violence. There is no published report on bladder rupture following
      trauma in pregnancy. We report a case of bladder injury following abdominal
      trauma in a pregnant woman.

PMID- 22413897
TI  - The influence of power dynamics and trust on multidisciplinary collaboration: a
      qualitative case study of type 2 diabetes mellitus.
AB  - BACKGROUND: Ongoing care for chronic conditions such as diabetes is best provided
      by a range of health professionals working together. There are challenges in
      achieving this where collaboration crosses organisational and sector boundaries.
      The aim of this article is to explore the influence of power dynamics and trust
      on collaboration between health professionals involved in the management of
      diabetes and their impact on patient experiences. METHODS: A qualitative case
      study conducted in a rural city in Australia. Forty five health service providers
      from nineteen organisations (including fee-for-service practices and block funded
      public sector services) and eight patients from two services were purposively
      recruited. Data was collected through semi-structured interviews that were audio
      taped and transcribed. A thematic analysis approach was used using a two-level
      coding scheme and cross-case comparisons. RESULTS: Three themes emerged in
      relation to power dynamics between health professionals: their use of power to
      protect their autonomy, power dynamics between private and public sector
      providers, and reducing their dependency on other health professionals to
      maintain their power. Despite the intention of government policies to support
      more shared decision-making, there is little evidence that this is happening. The
      major trust themes related to role perceptions, demonstrated competence, and the
      importance of good communication for the development of trust over time. The
      interaction between trust and role perceptions went beyond understanding each
      other's roles and professional identity. The level of trust related to the
      acceptance of each other's roles. The delivery of primary and community-based
      health services that crosses organisational boundaries adds a layer of complexity
      to interprofessional relationships. The roles of and role boundaries between and
      within professional groups and services are changing. The uncertainty and
      vulnerability associated with these changes has affected the level of trust and
      mistrust. CONCLUSIONS: Collaboration across organisational boundaries remains
      challenging. Power dynamics and trust affect the strategic choices made by each
      health professional about whether to collaborate, with whom, and to what level.
      These decisions directly influenced patient experiences. Unlike the difficulties
      in shifting the balance of power in interprofessional relationships, trust and
      respect can be fostered through a mix of interventions aimed at building personal
      relationships and establishing agreed rules that govern collaborative care and
      that are perceived as fair.

PMID- 22413898
TI  - The kinetics of lactate production and removal during whole-body exercise.
AB  - BACKGROUND: Based on a literature review, the current study aimed to construct
      mathematical models of lactate production and removal in both muscles and blood
      during steady state and at varying intensities during whole-body exercise. In
      order to experimentally test the models in dynamic situations, a cross-country
      skier performed laboratory tests while treadmill roller skiing, from where work
      rate, aerobic power and blood lactate concentration were measured. A two
      compartment simulation model for blood lactate production and removal was
      constructed. RESULTS: The simulated and experimental data differed less than 0.5
      mmol/L both during steady state and varying sub-maximal intensities. However, the
      simulation model for lactate removal after high exercise intensities seems to
      require further examination. CONCLUSIONS: Overall, the simulation models of
      lactate production and removal provide useful insight into the parameters that
      affect blood lactate response, and specifically how blood lactate concentration
      during practical training and testing in dynamical situations should be
      interpreted.

PMID- 22413899
TI  - Effects of modality change on health-related quality of life.
AB  - Patients with end-stage renal disease (ESRD) requiring renal replacement have
      impaired health-related quality of life (HRQoL), and there is general consensus
      that HRQoL improves with successful transplant and evidence of improvement with
      frequent hemodialysis. This study reports changes in HRQoL associated with
      changes in treatment modality to daily hemodialysis (DHD) and transplant among
      patients requiring renal replacement. This cohort study had assessments at
      baseline and 6-month following modality change. Subjects were nondiabetic
      individuals receiving conventional hemodialysis who (a) remained on conventional
      hemodialysis (n = 13), (b) changed to daily hemodialysis (DHD) (n = 10), or (c)
      received a living donor transplant (n = 20). Thirty-four healthy controls were
      assessed once for comparison. HRQoL was measured using the Kidney Disease Quality
      of Life Instrument. The Physical Functioning and Physical Composite Scale scores
      were primary outcomes. Transplantation resulted in significant improvements in
      six of eight generic scales and the physical composite scale (PCS). Those
      changing to DHD had significant improvements in Physical Function and PCS scales.
      Those remaining on dialysis remained lower than controls on all scales except for
      Vitality; the transplant group remained lower than controls only on the Vitality
      and General Health scales. Transplant resulted in significant improvements in
      four of the seven disease-specific scales (symptoms, effects, and burden of
      kidney disease, work). DHD resulted in improvements in the effects of kidney
      disease. Modality change to transplant results in significant improvement in
      HRQoL, achieving levels similar to controls. Change to daily hemodialysis
      improves only select HRQoL domains and remains low in disease-specific domains.

PMID- 22413900
TI  - HIV testing in community settings in resource-rich countries: a systematic review
      of the evidence.
AB  - OBJECTIVES: Community HIV testing represents an opportunity for diagnosing HIV
      infection among individuals who may not have contact with health services,
      especially in hard-to-reach groups. The aim of this review was to assess the
      evidence for feasibility, acceptability and effectiveness of HIV testing
      strategies in community settings in resource-rich countries. METHODS: The PubMed
      database was searched for English language studies of outreach HIV testing in
      resource-rich countries. Studies were included if they reported one of the
      following outcome measures: uptake of testing; seropositivity; client
      acceptability; or provider acceptability. RESULTS: Forty-four studies were
      identified; the majority took place in the USA and targeted men who have sex with
      men. Uptake of HIV testing varied between 9 and 95% (in 14 studies).
      Seropositivity was >= 1% in 30 of 34 studies. In 16 studies the proportion of
      patients who received their test results varied from 29 to 100% and rapid testing
      resulted in a higher proportion of clients receiving their results. Overall,
      client satisfaction with community HIV testing was high. However, concern
      remained over confidentiality, professional standards and the need for post-test
      counselling. Staff reported positive attitudes towards community testing.
      CONCLUSIONS: In the majority of studies, the reported seropositivity was higher
      than 1/1000, the threshold deemed to be cost-effective for routinely offering
      testing. Rapid testing improved the return of HIV test results to clients. HIV
      testing in outreach settings may be important in identifying undiagnosed
      infections in at-risk populations, but appropriate data to evaluate these
      initiatives must be collected.

PMID- 22413902
TI  - Computational study of isopropylbenzenium ions.
AB  - A theoretical investigation of the isopropylbenzenium ion system has been carried
      out with structures determined with B3LYP. Energies are calculated with the high
      accuracy composite methods, G3 (G3B3) and CBS (CBS-QB3). The main goal has been
      to resolve the following issue: Are there any stable ion pi-electron complexes of
      the type C(6)H(6)/C(3)H(7)(+) or C(6)H(7)(+)/C(3)H(6) in this system? Two minimum
      points on the potential energy surface (PES) corresponding to benzenium
      ion/propene complexes were found. Due to free internal rotation, they represent
      only one species. The barrier for forming an isopropylbenzenium ion from the
      complex is low, so the lifetime will be short. Computation of the IR spectrum of
      the complex shows that there is a very intense absorption line due to C-H
      stretching, in an otherwise empty region, that may be used to identify the
      complex, if present. No stable C(6)H(6)/C(3)H(7)(+) complex was found, but a
      quasi-stable species structurally corresponding to the earlier described stable
      C(6)H(6)/C(4)H(9)(+) complex was observed. A simplistic explanation why the
      benzene/isopropyl cation, in contrast to benzene/tert-butyl cation, does not form
      a stable ion/pi-electron complex is given.

PMID- 22413901
TI  - Neurotrophic actions of dopamine on the development of a serotonergic feeding
      circuit in Drosophila melanogaster.
AB  - BACKGROUND: In the fruit fly, Drosophila melanogaster, serotonin functions both
      as a neurotransmitter to regulate larval feeding, and in the development of the
      stomatogastric feeding circuit. There is an inverse relationship between neuronal
      serotonin levels during late embryogenesis and the complexity of the serotonergic
      fibers projecting from the larval brain to the foregut, which correlate with
      perturbations in feeding, the functional output of the circuit. Dopamine does not
      modulate larval feeding, and dopaminergic fibers do not innervate the larval
      foregut. Since dopamine can function in central nervous system development,
      separate from its role as a neurotransmitter, the role of neuronal dopamine was
      assessed on the development, and mature function, of the 5-HT larval feeding
      circuit. RESULTS: Both decreased and increased neuronal dopamine levels in late
      embryogenesis during development of this circuit result in depressed levels of
      larval feeding. Perturbations in neuronal dopamine during this developmental
      period also result in greater branch complexity of the serotonergic fibers
      innervating the gut, as well as increased size and number of the serotonin
      containing vesicles along the neurite length. This neurotrophic action for
      dopamine is modulated by the D2 dopamine receptor expressed during late
      embryogenesis in central 5-HT neurons. Animals carrying transgenic RNAi
      constructs to knock down both dopamine and serotonin synthesis in the central
      nervous system display normal feeding and fiber architecture. However, disparate
      levels of neuronal dopamine and serotonin during development of the circuit
      result in abnormal gut fiber architecture and feeding behavior. CONCLUSIONS:
      These results suggest that dopamine can exert a direct trophic influence on the
      development of a specific neural circuit, and that dopamine and serotonin may
      interact with each other to generate the neural architecture necessary for normal
      function of the circuit.

PMID- 22413903
TI  - Ferric carboxymaltose for the treatment of iron-deficiency anemia. [corrected].
AB  - INTRODUCTION: Anemic patients may benefit from the various intravenous iron
      replacement options available. Ferric carboxymaltose (FCM) is a new iron
      formulation (150 kDa) that can be given at high doses (20 mg/kg, up to 1000 mg)
      over a short period (<= 15 min), without test dosing. AREAS COVERED: This paper
      reviews studies dealing with the efficacy and safety of FCM for treating anemia
      in relatively large numbers of patients, in addition to analyzing the differences
      regarding clinical conditions, iron doses, follow-up, comparators, and
      hematologic response targets. EXPERT OPINION: Overall, there is substantial
      evidence that FCM is effective in treating iron-deficiency anemia in many acute
      and chronic conditions, with a favorable benefit-risk profile. The efficacy of
      FCM for correcting anemia is similar to that of iron sucrose, and it is superior
      to oral iron or placebo in replenishing iron stores. Despite higher acquisition
      costs (as fewer administrations are needed), treatment with FCM (as well as with
      iron isomaltoside 1000 or ferumoxytol) seems to be cost-effective when compared
      to iron sucrose, and is more convenient for patients. There are, however, some
      aspects (such as hypophosphatemia) and important missing information (such as use
      in children and pregnant women) that need to be addressed for facilitating a
      widespread use of FCM.

PMID- 22413904
TI  - Manganese oxides with rod-, wire-, tube-, and flower-like morphologies: highly
      effective catalysts for the removal of toluene.
AB  - Nanosized rod-like, wire-like, and tubular alpha-MnO(2) and flower-like spherical
      Mn(2)O(3) have been prepared via the hydrothermal method and the CCl(4) solution
      method, respectively. The physicochemical properties of the materials were
      characterized using numerous analytical techniques. The catalytic activities of
      the catalysts were evaluated for toluene oxidation. It is shown that alpha-MnO(2)
      nanorods, nanowires, and nanotubes with a surface area of 45-83 m(2)/g were
      tetragonal in crystal structure, whereas flower-like spherical Mn(2)O(3) with a
      surface area of 162 m(2)/g was of cubic crystal structure. There were the
      presence of surface Mn ions in multiple oxidation states (e.g., Mn(3+), Mn(4+),
      or even Mn(2+)) and the formation of surface oxygen vacancies. The oxygen
      adspecies concentration and low-temperature reducibility decreased in the order
      of rod-like alpha-MnO(2) > tube-like alpha-MnO(2) > flower-like Mn(2)O(3) > wire
      like alpha-MnO(2), in good agreement with the sequence of the catalytic
      performance of these samples. The best-performing rod-like alpha-MnO(2) catalyst
      could effectively catalyze the total oxidation of toluene at lower temperatures
      (T(50%) = 210  degrees C and T(90%) = 225  degrees C at space velocity = 20,000
      mL/(g h)). It is concluded that the excellent catalytic performance of alpha
      MnO(2) nanorods might be associated with the high oxygen adspecies concentration
      and good low-temperature reducibility. We are sure that such one-dimensional well
      defined morphological manganese oxides are promising materials for the catalytic
      elimination of air pollutants.

PMID- 22413905
TI  - Wire assisted transpancreatic septotomy, needle knife precut or both for
      difficult biliary access.
AB  - BACKGROUND AND AIMS: Pre-cut techniques, the most commonly described being needle
      knife papillotomy (NK), have been used to facilitate biliary access in failed
      standard biliary cannulation (BC). Transpancreatic septotomy (TS) is a pre-cut
      technique with limited outcome data. We aim to assess the outcomes of wire
      assisted transpancreatic septotomy (WTS) as the primary pre-cut technique after
      initial failed attempted BC and to compare these with outcomes of primary NK.
      METHODS: We retrospectively reviewed all endoscopic retrograde
      cholangiopancreatographies (ERCPs) performed by endoscopists who performed WTS
      over a 3-year period. We selected cases where WTS and/or NK were performed, and
      these cases were reviewed to assess for procedure related complications and BC
      success. RESULTS: During the study period 1336 ERCPs were performed. WTS was
      performed in 53 cases. In seven cases WTS and NK were performed sequentially
      (resulting in immediate cannulation in all these cases). Immediate BC was
      achieved on first attempt in 36 (68%) WTS cases and in a further 14 cases on a
      repeat attempt (cumulative BC rate 94%). During the same period 66 (5%) patients
      underwent primary NK. In these cases initial cannulation was achieved in 50 (76%)
      cases and cannulation on repeat attempt in six cases (cumulative success rate
      85%). Complications occurred in three WTS patients (5.6%) and seven NK patients
      (10.6%). The differences were not statistically significant. CONCLUSIONS: Wire
      assisted transpancreatic septotomy is a safe and effective alternative technique
      to traditional NK in patients who have failed standard BC techniques. It also
      allows other pre-cut techniques such as NK to be used should initial WTS be
      unsuccessful.

PMID- 22413906
TI  - Inhibition of p38 kinase suppresses the development of psoriasis-like lesions in
      a human skin transplant model of psoriasis.

PMID- 22413907
TI  - Value-added uses for crude glycerol--a byproduct of biodiesel production.
AB  - Biodiesel is a promising alternative, and renewable, fuel. As its production
      increases, so does production of the principle co-product, crude glycerol. The
      effective utilization of crude glycerol will contribute to the viability of
      biodiesel. In this review, composition and quality factors of crude glycerol are
      discussed. The value-added utilization opportunities of crude glycerol are
      reviewed. The majority of crude glycerol is used as feedstock for production of
      other value-added chemicals, followed by animal feeds.

PMID- 22413908
TI  - Passive smoke exposure of female rats caused aortic atherosclerotic precursor
      lesions in their offspring.
AB  - The aim of this study was to evaluate the presence and degree of preclinical
      atherosclerosis in pups of pregnant rats exposed to cigarette smoke. Abdominal
      aorta examined for atherosclerotic lesions and intimal medial thickness of the
      abdominal aorta was measured by image analysis. The study groups showed
      endothelial cellular losses, marked intimal injuries, elastic fiber damages,
      mononuclear cellular infiltration, and irregularities in internal elastic
      membrane, with pronounced damages as integrity losses and local fragmentations.
      The results provide evidence for development of an atherosclerotic process in the
      neonatal period, even in prenatal stage, long before the formation of smoke
      related cardiovascular diseases.

PMID- 22413909
TI  - The machine body metaphor: From science and technology to physical education and
      sport, in France (1825-1935).
AB  - The long history of the conception of physical exercise in France may be viewed
      as a function of a series of changes in understanding the body. Scientific
      concepts were used to present the body in official texts by authors specializing
      in the subject, or to describe them, as did Michel Foucault, as epistemic
      changes. A departure occurred during the 19th century that is clearly
      demonstrated in the writings of Gustave Adolphe Hirn. This breakthrough concerned
      the idea of considering the organism as an energy-generating machine. This
      metaphor was employed in describing the body during physical exercise from the
      17th to the 19th centuries, when the body was thought of as mechanical. Such
      metaphors were used by the most relevant figures writing at the end of the 19th
      century in the rationale that is examined in this paper. It shows how Hirn,
      Marey, Lagrange, Demenij, Hebert, and Tissie saw the body and how they employed
      machine metaphors when referring to it. These machine metaphors are analyzed from
      the time of their scientific and technological origins up to their current use in
      physical and sports education. This analysis will contribute to the understanding
      of how a scientific metaphor comes to be in common use and may lead to particular
      exercise practices.

PMID- 22413910
TI  - Targeting native adult heart progenitors with cardiogenic small molecules.
AB  - Targeting native progenitors with small molecule pharmaceuticals that direct cell
      fate decisions is an attractive approach for regenerative medicine. Here, we show
      that 3,5-disubstituted isoxazoles (Isx), stem cell-modulator small molecules
      originally recovered in a P19 embryonal carcinoma cell-based screen, directed
      cardiac muscle gene expression in vivo in target tissues of adult transgenic
      reporter mice. Isx also stimulated adult mouse myocardial cell cycle activity.
      Narrowing our focus onto one target cardiac-resident progenitor population, Isx
      directed muscle transcriptional programs in vivo in multipotent Notch-activated
      epicardium-derived cells (NECs), generating Notch-activated adult cardiomyocyte
      like precursors. Myocardial infarction (MI) preemptively differentiated NECs
      toward fibroblast lineages, overriding Isx's cardiogenic influence in this cell
      population. Isx dysregulated gene expression in vivo in Notch-activated repair
      fibroblasts, driving distinctive (pro-angiogenesis) gene programs, but failed to
      mitigate fibrosis or avert ventricular functional decline after MI. In NECs in
      vitro, Isx directed partial muscle differentiation, which included biosynthesis
      and assembly of sarcomeric alpha-actinin premyofibrils, beaded structures
      pathognomonic of early developing cardiomyocytes. Thus, although Isx small
      molecules have promising in vivo efficacy at the level of cardiac muscle gene
      expression in native multipotent progenitors and are first in class in this
      regard, a greater understanding of the dynamic interplay between fibrosis and
      cardiogenic small molecule signals will be required to pharmacologically enable
      regenerative repair of the heart.

PMID- 22413911
TI  - Antineoplastic agents. 587. Isolation and structure of 3-epipancratistatin from
      Narcissus cv. Ice Follies.
AB  - Bioassay-guided (cancer cell line) separation of an extract prepared from
      Narcissus cv. Ice Follies (from The Netherlands) led to the isolation of a new
      Amaryllidaceae isocarbostiryl, 3-epipancratistatin (1b), as well as narciclasine
      (2). This Narcissus cultivar was found to be a good source of narciclasine. The
      structure of 1b was established by high-resolution mass and high-field 2D NMR
      spectroscopic analyses. Against a panel of murine and human cancer cell lines, 3
      epipancratistatin (1b) led to cell growth inhibition (GI(50) 2.2-0.69 MUg/mL)
      some 100* less than that found for pancratistatin (1a) and narciclasine (2),
      thereby revealing an important configurational requirement in 1a for strong
      cancer cell growth inhibition.

PMID- 22413913
TI  - Are platelet volume indices of clinical use? A multidisciplinary review.
AB  - Platelet size correlates with platelet activity and can be assessed by platelet
      volume indices (PVI). The PVI, mean platelet volume (MPV), is universally
      available with routine blood counts by automated hemograms and therefore is an
      attractive index to study in clinical scenarios. PVI are useful in assessing the
      etiology of thrombocytopenia. In addition, a normal platelet distribution width
      in the setting of thrombocytosis is highly suggestive of a reactive etiology.
      Higher MPV is also associated with the presence of cardiovascular risk factors,
      chest pain due to acute coronary syndrome, and adverse outcome after acute
      coronary syndrome. Results from studies evaluating MPV in patients with
      peripheral artery disease, unprovoked deep vein thrombosis, and pulmonary
      embolism further advocate a potential role for MPV in identifying patients at
      high risk of thrombosis. Nevertheless, most of these data come from retrospective
      studies some of which have small study populations and confounding factors
      influencing platelet volume. Moreover, the cut-off values derived from these
      retrospective studies have not been validated prospectively. Despite the
      potential for clinical utility evident from these studies, the above-mentioned
      flaws together with technical problems in measuring MPV currently limit its
      clinical usefulness. Our review provides a perspective on PVI's potential
      clinical use.

PMID- 22413912
TI  - Update on diastolic heart failure or heart failure with preserved ejection
      fraction in the older adults.
AB  - Nearly half of all heart failure (HF) patients have diastolic HF (DHF) or
      clinical HF with normal or near-normal left ventricular ejection fraction (LVEF).
      Although the terminology has not been clearly defined, it is increasingly being
      referred to as HF with preserved ejection fraction (HFPEF). The prevalence of
      HFPEF increases with age, especially among older women. Identifying HFPEF is
      important because the etiology, pathogenesis, prognosis, and optimal management
      may differ from that for systolic HF (SHF) or HF with reduced ejection fraction.
      The clinical presentation of HF is similar for both SHF and HFPEF. As in SHF,
      HFPEF is a clinical diagnosis. Once a clinical diagnosis of HF has been made, the
      presence of HFPEF can be established by confirming a normal or near-normal LVEF,
      often by an echocardiogram. HFPEF is often associated with a history of
      hypertension, concentric left ventricular hypertrophy, vascular stiffness, and
      left ventricular diastolic dysfunction. As in SHF, HFPEF is also associated with
      poor outcomes. While therapies with angiotensin-converting enzyme inhibitors and
      beta-blockers improve outcomes in SHF, there is currently no such evidence of
      their benefits in older HFPEF patients. In this review recent advances in the
      diagnosis and management of HFPEF in older adults are discussed.

PMID- 22413914
TI  - Modified parainguinal approach for cystic calculus removal in five equids.
AB  - This report describes a modification of the parainguinal approach for removal of
      cystic calculi: a ventral midline laparotomy-guided parainguinal laparocystotomy.
      The ventral midline approach to the abdomen is rapid and routinely used by equine
      surgeons. With an arm introduced to the abdomen via the ventral midline, the
      surgeon is able to select the ideal parainguinal laparotomy incision location
      that allows bladder exteriorisation with the minimum amount of tension. Because
      the surgeon's hand is introduced via the ventral midline incision, the
      parainguinal incision can be sized to just allow exteriorisation of the urinary
      bladder and urolith, increasing extra-abdominal bladder security during cystotomy
      while reducing incision size in the parainguinal region. Finally, an assistant's
      hand via the ventral midline incision can maintain bladder stability within the
      parainguinal incision during cystotomy closure.

PMID- 22413915
TI  - The uncommon combination of common variable immunodeficiency, macrophage
      activation syndrome, and cytomegalovirus retinitis.
AB  - Common variable immunodeficiency (CVID) is a heterogeneous group of disorders
      with varied immunologic phenotypes and clinical manifestations. Patients with
      CVID are mainly characterized by decreased serum immunoglobulin levels, and
      increased susceptibility to recurrent bacterial infections, autoimmune disorders,
      and malignancies. Here we present a CVID patient who has developed a clinical
      polyclonal lymphocytic infiltration phenotype associated with severe and
      irreversible pancytopenia with unknown etiology. Progressive unilateral loss of
      vision and cytomegalovirus retinitis indicated the cause of patient's
      pancytopenia.

PMID- 22413916
TI  - Exogenous nef induces proinflammatory signaling events in murine macrophages.
AB  - Despite the fact that murine cells are not permissive for human immunodeficiency
      virus type 1 (HIV-1) infection, several investigators have constructed transgenic
      (Tg) mice to model HIV-1-induced diseases to overcome this restriction. The
      generation of Tg mice expressing selected HIV-1 genes revealed that Nef harbors a
      major disease determinant. HIV-1 Nef protein is a molecular adapter able to
      interact with several cellular partners, interfering with cellular functions. The
      phenotype of Nef Tg mice was extensively characterized regarding in vivo
      development of AIDS-like disease and the effects of Nef expression in T
      lymphocytes, but the functions eventually corrupted by Nef in monocytes and
      macrophages were less studied. Nef treatment of human monocyte-derived
      macrophages induces the internalization of the protein and modulates the
      production and secretion of different chemokines and cytokines by activating
      specific intracellular signaling pathways (i.e., NF-kappaB, MAPK, and IRF3).
      Therefore we set up an in vitro murine macrophage-based model using stabilized
      cell lines and primary peritoneal macrophages, and treated them with recombinant
      myristoylated Nef(SF2) (recNef). Like human cells, murine macrophages responded
      to Nef treatment, activating IKK-alpha and IKK-beta, JNK, and p38 MAP kinases.
      Activation of the NF-kappaB pathway is mandatory for the synthesis and release of
      a pool of cytokines and chemokines, including IFN-beta, that induce tyrosine
      phosphorylation of the signal transducer and activator of transcription (STAT)-1,
      STAT-2, and STAT-3, in an autocrine and paracrine manner, confirming that murine
      macrophages respond to Nef similarly to human ones. These data extend the results
      previously obtained in human primary macrophages, allowing the use of murine
      cells in culture to study signaling events modulated by Nef in myeloid-derived
      cells. In particular, it may be feasible to use macrophages derived from mice
      knocked out in specific signaling intermediates to obtain greater insight into
      the mechanism of Nef-induced effects.

PMID- 22413917
TI  - Yoshiki Hotta and the dawn of zebrafish molecular neurogenetics in Japan.
AB  - Abstract: After coming back to Japan to work in the Department of Physics at the
      University of Tokyo, Yoshiki Hotta spent a year or so on searching for behavioral
      mutants of goldfish. Although this endeavor did not succeed, he remained an
      adamant supporter of the development of zebrafish research in Japan. Here we
      review how his support helped zebrafish neurogenetics in Japan gain a unique
      position in the world research community.

PMID- 22413918
TI  - IR-spectrophotoelectrochemical characterization of mesoporous semiconductor
      films.
AB  - A combined IR-spectroscopic and electrochemical approach for the study of photo-
      and bias-induced reactions at the semiconductor/electrolyte interface is
      presented. Information on the electronic structure of a mesoporous semiconductor
      nanoparticle network, concretely the density and distribution of band gap states,
      as well as the nature of solution species are analyzed in situ. It has been shown
      that under appropriate conditions the electrode potential determines the quasi
      Fermi level throughout the mesoporous film and thus the occupation of IR-active
      band gap states, independently of the type of external perturbation, i.e.,
      application of a bias voltage or electrode exposure to photons exceeding the
      semiconductor band gap at open circuit. Importantly, electronic properties of the
      semiconductor and vibrational properties of solution species can be addressed
      simultaneously by IR-spectroscopy. In addition, electrochemical methods provide a
      means for the active manipulation (in potentiostatic measurements) or the passive
      tracking (during open circuit potential decay) of the quasi-Fermi level in the
      mesoporous film together with the possibility of electron quantification (by
      charge extraction experiments).

PMID- 22413919
TI  - Association of serum adipocytokine levels with cardiac autonomic neuropathy in
      type 2 diabetic patients.
AB  - BACKGROUND: Cardiac autonomic neuropathy (CAN) is a common complication of
      diabetes associated with poor prognosis. In addition, the autonomic imbalance is
      associated with cardiovascular disease (CVD) in diabetes. It is thought that
      adipocytokines contribute to the increased risk of vascular complications in
      patients with type 2 diabetes mellitus (T2DM). However, literature data on the
      association between CAN with adipocytokines such as leptin, tumor necrosis factor
      alpha (TNF-alpha), adiponectin in subjects with T2DM is limited.Therefore, in the
      present study, we examined the relationship between fasting serum leptin, TNF-
      alpha and adiponectin and CAN in Korean T2DM patients. METHODS: A total of 142
      T2DM patients (94 males, 48 females) were recruited. CAN was assessed by the five
      tests according to the Ewing's protocol and the time and frequency domain of the
      heart rate variability (HRV) was evaluated. Serum TNF-alpha and adiponectin
      levels were measured using enzyme-linked immunosorbent assay and serum leptin
      levels were measured using radioimmunoassay. RESULTS: Although, the mean levels
      of leptin, TNF-alpha and adiponectin were not significantly different between the
      groups with and without CAN, the levels of leptin and adiponectin had a tendency
      to increase as the score of CAN increased (p = 0.05, p = 0.036). Serum leptin
      levels demonstrated a negative correlation with low frequency (LF) in the upright
      position (p = 0.037). Regarding TNF-alpha, a significant negative correlation was
      observed with SDNN and RMSSD in the upright position (p = 0.023, p = 0.019).
      Adiponectin levels were not related to any HRV parameters. Multivariate logistic
      regression analysis demonstrated that the odds of CAN increased with a longer
      duration of diabetes (1.25, [1.07-1.47]) and higher homeostatic model of
      assessment-insulin resistance (HOMA-IR) (5.47, [1.8-16.5]). The relative risks
      for the presence of CAN were 14.1 and 51.6 for the adiponectin 2nd, 3rd tertiles
      when compared with first tertile (p-value for trend = 0.022). CONCLUSIONS: In the
      present study, the higher serum adiponectin levels and HOMA-IR were associated
      with an increased risk for the presence of CAN. Also, the CAN score correlated
      with the serum adiponectin. Serum adipocytokines such as leptin and TNF-alpha
      were significantly correlated with parameters of HRV, representative markers of
      CAN. Future prospective studies with larger number of patients are required to
      establish a direct relationship between plasma adipocytokine concentrations and
      the development or severity of CAN.

PMID- 22413920
TI  - An analysis of patients' understanding of 'routine' preoperative blood tests and
      HIV screening. Is no news really good news?
AB  - OBJECTIVES: Many patients may believe that HIV screening is included in routine
      preoperative work-ups. We examined what proportion of patients undergoing
      preoperative blood testing believed that they had been tested for HIV. METHODS:
      All patients hospitalized for elective orthopaedic surgery between January and
      December 2007 were contacted and asked to participate in a 15-min computer
      assisted telephone interview (n = 1330). The primary outcome was to determine
      which preoperative tests patients believed had been performed from a choice of
      glucose, clotting, HIV serology and cholesterol, and what percentage of patients
      interpreted the lack of result communication as a normal or negative test. The
      proportion of patients agreeable to HIV screening prior to future surgery was
      also determined. RESULTS: A total of 991 patients (75%) completed the
      questionnaire. Three hundred and seventy-five of these 991 patients (38%)
      believed incorrectly that they had been tested for HIV preoperatively. Younger
      patients were significantly more likely to believe that an HIV test had been
      performed (mean age 46 vs. 50 years for those who did not believe that an HIV
      test had been performed; P < 0.0001). Of the patients who believed that a test
      had been performed but received no result, 96% interpreted lack of a result as a
      negative HIV test. Over 80% of patients surveyed stated that they would agree to
      routine HIV screening prior to future surgery. A higher acceptance rate was
      associated with younger age (mean age 47 years for those who would agree vs. 56
      years for those who would not; P < 0.0001) and male sex ( P < 0.009).
      CONCLUSIONS: Many patients believe that a preoperative blood test routinely
      screens for HIV. The incorrect assumption that a lack of result communication
      indicates a negative test may contribute to delays in HIV diagnoses.

PMID- 22413921
TI  - Detection of vertical root fractures by conventional radiographic examination and
      cone beam computed tomography - an in vitro analysis.
AB  - OBJECTIVES:  This study compared the ability of conventional radiographic and
      cone beam computed tomography (CBCT) examinations to detect vertical root
      fractures (VRF) in teeth with or without root canal treatment and metallic posts.
      Furthermore, the influence of using different voxel sizes from CBCT images was
      assessed. METHODOLOGY:  Sixty single-rooted human teeth were randomly divided
      into two groups: experimental and control. Twenty teeth were endodontically
      prepared and obturated with gutta-percha, twenty had a metallic postcemented
      after the filling, and twenty had no preparation. The teeth from the experimental
      group were fractured. All teeth were radiographed with three different horizontal
      angles, and after, CBCT images were acquired following three protocols in which
      the variation was the voxel resolution (0.4, 0.3, and 0.2 mm). Three calibrated
      examiners assessed the images. RESULTS:  Chi-squared test showed no statistical
      difference among the images in detecting VRFs. The results of the diagnostic
      performance tests presented similar ability to detect VRFs when conventional
      radiographic examination was compared with 0.2 and 0.3-voxel CBCTs scans, in
      roots without endodontic treatment and metallic post. Moreover, specificity,
      sensitivity, and accuracy findings were similar for both 0.2 and 0.3-voxel
      resolution scans for teeth that are not root filled. However, it was observed
      that in teeth with root canal treatment and a post, the accuracy was higher when
      0.2-mm voxel resolution was used. CONCLUSION:  The radiographic examination with
      horizontal angle variation should be encouraged as the first complementary
      approach to assess the presence of VRFs. If conventional imaging is not capable
      to provide adequate information, CBCT can be indicated if a root fracture is
      strongly suspected. The root condition should then guide the voxel resolution
      choice, selecting 0.3-voxel for not root filled teeth and 0.2-voxel for teeth
      with filling and/or a post.

PMID- 22413922
TI  - Hysteroscopy after uterine fibroid embolization: evaluation of intrauterine
      findings in 127 patients.
AB  - AIM: Several atypical hysteroscopy findings have been described in association
      with uterine artery embolization (UAE). The purpose of this study was to evaluate
      the types and frequency of these findings in the largest published series of
      patients. MATERIAL AND METHODS: Premenopausal patients after bilateral UAE for
      symptomatic intramural fibroid underwent subsequent hysteroscopic examination 3-9
      months following UAE. The uterine cavity was examined with focus on specific post
      embolization changes. Biopsy of endometrium was obtained and evaluated together
      with a biopsy of abnormal foci if present. RESULTS: UAE was performed in a total
      of 127 women with an average size of dominant fibroid 63.1 mm in diameter and an
      average patient age of 35.1 years. Even though the majority of patients were
      asymptomatic at the time of hysteroscopy (78.0%), the post-embolization
      hysteroscopic examination was normal in only 51 patients (40.2%). The most
      frequent abnormalities included tissue necrosis (52 women, 40.9%), intracavitary
      myoma protrusion (45 women, 35.4%), endometrium 'spots' (22.1%), intrauterine
      synechiae (10.2%) and 'fistula' between the uterine cavity and intramural fibroid
      (6.3%). Histopathological examination showed normal, secretory or proliferative
      endometrium in 83.5% patients. Necrosis and/or hyalinization prevailed in the
      results of biopsy of abnormal loci (45 cases, 35.4%). CONCLUSION: Frequency of
      abnormal hysteroscopic findings several months after UAE for primary intramural
      myomas is high. Alarmingly high is the percentage of patients with a
      histopathologically verified necrosis. Performing hysteroscopy in selected
      patients after UAE is necessary before eventual surgical re-intervention,
      especially in women with reproductive plans.

PMID- 22413923
TI  - Ongoing monitoring of data clustering in multicenter studies.
AB  - BACKGROUND: Multicenter study designs have several advantages, but the
      possibility of non-random measurement error resulting from procedural differences
      between the centers is a special concern. While it is possible to address and
      correct for some measurement error through statistical analysis, proactive data
      monitoring is essential to ensure high-quality data collection. METHODS: In this
      article, we describe quality assurance efforts aimed at reducing the effect of
      measurement error in a recent follow-up of a large cluster-randomized controlled
      trial through periodic evaluation of intraclass correlation coefficients (ICCs)
      for continuous measurements. An ICC of 0 indicates the variance in the data is
      not due to variation between the centers, and thus the data are not clustered by
      center. RESULTS: Through our review of early data downloads, we identified
      several outcomes (including sitting height, waist circumference, and systolic
      blood pressure) with higher than expected ICC values. Further investigation
      revealed variations in the procedures used by pediatricians to measure these
      outcomes. We addressed these procedural inconsistencies through written
      clarification of the protocol and refresher training workshops with the
      pediatricians. Further data monitoring at subsequent downloads showed that these
      efforts had a beneficial effect on data quality (sitting height ICC decreased
      from 0.92 to 0.03, waist circumference from 0.10 to 0.07, and systolic blood
      pressure from 0.16 to 0.12). CONCLUSIONS: We describe a simple but formal
      mechanism for identifying ongoing problems during data collection. The
      calculation of the ICC can easily be programmed and the mechanism has wide
      applicability, not just to cluster randomized controlled trials but to any study
      with multiple centers or with multiple observers.

PMID- 22413925
TI  - Reversed freeze quench method near the solvent phase transition.
AB  - Freeze quenching is a general method for trapping reaction intermediates on a
      (sub)millisecond time scale. The method relies on a mixing and subsequent rapid
      freezing of solutions of reactants. If the reaction is limited by diffusion, it
      may be advantageous to initially mix the reactants under conditions where the
      reaction does not proceed, e.g., by mixing them at low temperature as solids. The
      temperature may then be raised close to the melting point of the solvent.
      Depending on the viscosity of the solvent, the temperature can be raised either
      by heating or by applying laser pulses of nanosecond length with concomitant
      conversion of light into heat. A reduction of the dead time and a good control of
      the reaction speed in comparison to the standard freeze quench technique has been
      achieved with this method. The feasibility of the method in combination with EPR
      spectroscopy is verified by examining the important prototypical reductions of
      benzoquinone and 2,6-dichlorophenolindophenol by ascorbate as representatives for
      two-step redox reactions. By using light pulses of a laser, the reaction could be
      driven with rates lowered by 4 orders of magnitude as compared to room
      temperature reaction rates. This has allowed the observation of previously
      unobserved radical intermediates: the reduction of DCPIP by ascorbate is found to
      be strongly pH dependent. It proceeds via two one-electron steps at low pH,
      whereas at neutral pH, the reduction of DCPIP by ascorbate proceeds in a 1:2
      stoichiometry followed by a disproportionation of the ascorbate radicals.

PMID- 22413926
TI  - Dichotomy in the definition of prescriptive information suggests both prescribed
      data and prescribed algorithms: biosemiotics applications in genomic systems.
AB  - The fields of molecular biology and computer science have cooperated over recent
      years to create a synergy between the cybernetic and biosemiotic relationship
      found in cellular genomics to that of information and language found in
      computational systems. Biological information frequently manifests its "meaning"
      through instruction or actual production of formal bio-function. Such information
      is called prescriptive information (PI). PI programs organize and execute a
      prescribed set of choices. Closer examination of this term in cellular systems
      has led to a dichotomy in its definition suggesting both prescribed data and
      prescribed algorithms are constituents of PI. This paper looks at this dichotomy
      as expressed in both the genetic code and in the central dogma of protein
      synthesis. An example of a genetic algorithm is modeled after the ribosome, and
      an examination of the protein synthesis process is used to differentiate PI data
      from PI algorithms.

PMID- 22413927
TI  - Efficacy and safety of biologics in erythrodermic psoriasis: a multicentre,
      retrospective study.
AB  - BACKGROUND: Even though efficacy of biologics has been extensively studied in
      psoriasis vulgaris, studies in erythrodermic psoriasis, the most severe form of
      the disease, have been scarcely reported. OBJECTIVES: To address the efficacy and
      safety of biologics in patients with erythrodermic psoriasis. METHODS: A
      multicentre national retrospective study was performed using the French Psoriasis
      Group network. Patients showing psoriasis involving at least 90% of body surface
      area (BSA), and in whom severity of the disease had been evaluated before and
      after 3 and/or 6 months of treatment with biologics, were enrolled in the study.
      Results were expressed using intention-to-treat analysis. RESULTS: We included 28
      patients, representing 42 flares of erythrodermic psoriasis treated with
      infliximab (n=24), adalimumab (n=7), etanercept (n=6), ustekinumab (n=3) or
      efalizumab (n=2). A 75% improvement of BSA or Psoriais Area and Severity Index 12
      14 weeks after treatment onset was reached in 48% of flares treated with
      infliximab, in 50% of those treated with adalimumab and in 40% of those treated
      with etanercept. Twelve serious adverse events, consisting of bacterial infection
      in seven of them, were observed. Biological treatment was discontinued for safety
      concern in 19% of cases. A given biologic was administered for up to 48 weeks in
      34% of flares. CONCLUSIONS: Biologics show overall good short-term efficacy, but
      treatment switch due to lack of efficacy or side-effects is frequently observed
      on a longer term, with only one-third of patients still receiving the same drug
      after 1 year. The most significant safety concern consists of severe infections.

PMID- 22413928
TI  - Proteus syndrome: three case reports with a review of the literature.
AB  - Proteus syndrome (PS) is a rare, progressive disorder that manifests as
      asymmetric, disproportionate overgrowth affecting tissues derived from any
      germline layer. Cases of PS from 2005-2010 were retrieved from the pathology
      files at our institution. Two confirmed cases and one possible case of PS were
      identified. All patients came from different ethnic backgrounds. Patient 1
      displayed classic skin and overgrowth lesions. Patient 2 displayed various
      features, particularly vascular malformations. Patient 3 demonstrated a
      cerebriform connective tissue nevus alone. These patients demonstrate the
      spectrum of presentations of PS. Much is left to learn about this disfiguring
      disease.

PMID- 22413929
TI  - Cellular translocation of a gamma-AApeptide mimetic of Tat peptide.
AB  - Cell-penetrating peptides including the trans-activating transcriptional
      activator (Tat) from HIV-1 have been used as carriers for intracellular delivery
      of a myriad of cargoes including drugs, molecular probes, DNAs and nanoparticles.
      Utilizing fluorescence flow cytometry and confocal fluorescence microscopy, we
      demonstrate that a gamma-AApeptide mimetic of Tat (48-57) can cross the cell
      membranes and enter the cytoplasm and nucleus of cells, with efficiency
      comparable to or better than that of Tat peptide (48-57). Deletion of the four
      side chains of the gamma-AApeptide attenuates translocation capability. We also
      establish that the gamma-AApeptide is even less toxic than the Tat peptide
      against mammalian cells. In addition to their low toxicity, gamma-AApeptides are
      resistant to protease degradation, which may prove to be advantageous over alpha
      peptides for further development of molecular transporters for intracellular
      delivery.

PMID- 22413930
TI  - Premature luteal regression in a pregnant mare and subsequent pregnancy
      maintenance with the use of oral altrenogest.
AB  - Premature luteal demise or luteal insufficiency is not well characterised as a
      cause of pregnancy loss in domestic species, including horses. In this report, a
      mare inseminated with cooled-transported semen at our facility returned for a
      routine pregnancy diagnosis at 15 days post ovulation. Ultrasonography per rectum
      revealed endometrial oedema and the absence of visual indication of a corpus
      luteum on either ovary. Nonetheless, an embryonic vesicle small for the
      gestational age was identified. Daily oral altrenogest treatment was implemented
      immediately. Serum progesterone concentration was 0.67 ng/ml, which is below the
      threshold considered adequate for pregnancy maintenance in the mare. Examinations
      were repeated at 17, 25, 30, 39, 49, 72 and 120 days post ovulation. At 25 days
      post ovulation the embryonic vesicle presented normal development for the
      gestational age. In addition, sequential blood samples were collected to measure
      progesterone, equine chorionic gonadotrophin and oestrone sulphate
      concentrations. Although progesterone concentration did not exceed 2 ng/ml until
      72 days post ovulation, all other results were unremarkable and a healthy filly
      was born uneventfully at 344 days post ovulation.

PMID- 22413932
TI  - The Hotta neurogenetics school.

PMID- 22413931
TI  - Assessing validity of a short food frequency questionnaire on present dietary
      intake of elderly Icelanders.
AB  - BACKGROUND: Few studies exist on the validity of food frequency questionnaires
      (FFQs) administered to elderly people. The aim of this study was to assess the
      validity of a short FFQ on present dietary intake, developed specially for the
      AGES-Reykjavik Study, which includes 5,764 elderly individuals. Assessing the
      validity of FFQs is essential before they are used in studies on diet-related
      disease risk and health outcomes. METHOD: 128 healthy elderly participants (74 y
      +/- 5.7; 58.6% female) answered the AGES-FFQ, and subsequently filled out a 3-day
      weighed food record. Validity of the AGES-FFQ was assessed by comparing its
      answers to the dietary data obtained from the weighed food records, using
      Spearman's rank correlation, Chi-Square/Kendall's tau, and a Jonckheere-Terpstra
      test for trend. RESULT: For men a correlation >= 0.4 was found for potatoes,
      fresh fruits, oatmeal/muesli, cakes/cookies, candy, dairy products, milk, pure
      fruit juice, cod liver oil, coffee, tea and sugar in coffee/tea (r = 0.40-0.71).
      A lower, but acceptable, correlation was also found for raw vegetables (r =
      0.33). The highest correlation for women was found for consumption of rye bread,
      oatmeal/muesli, raw vegetables, candy, dairy products, milk, pure fruit juice,
      cod liver oil, coffee and tea (r = 0.40-0.61). An acceptable correlation was also
      found for fish topping/salad, fresh fruit, blood/liver sausage, whole-wheat
      bread, and sugar in coffee/tea (r = 0.28-0.37). Questions on meat/fish meals,
      cooked vegetables and soft drinks did not show a significant correlation to the
      reference method. Pearson Chi-Square and Kendall's tau showed similar results, as
      did the Jonckheere-Terpstra trend test. CONCLUSION: A majority of the questions
      in the AGES-FFQ had an acceptable correlation and may be used to rank individuals
      according to their level of intake of several important foods/food groups. The
      AGES-FFQ on present diet may therefore be used to study the relationship between
      consumption of several specific foods/food groups and various health-related
      endpoints gathered in the AGES-Reykjavik Study.

PMID- 22413933
TI  - Ultrasensitive vapor detection with surface-enhanced Raman scattering-active gold
      nanoparticle immobilized flow-through multihole capillaries.
AB  - We developed novel flow-through surface-enhanced Raman scattering (SERS)
      platforms using gold nanoparticle (Au-NP) immobilized multihole capillaries for
      rapid and sensitive vapor detection. The multihole capillaries consisting of
      thousands of micrometer-sized flow-through channels provide many unique
      characteristics for vapor detection. Most importantly, its three-dimensional SERS
      active micro-/nanostructures make available multilayered assembly of Au-NPs,
      which greatly increase SERS-active surface area within a focal volume of
      excitation and collection, thus improving the detection sensitivity. In addition,
      the multihole capillary's inherent longitudinal channels offer rapid and
      convenient vapor delivery, yet its micrometer-sized holes increase the
      interaction between vapor molecules and SERS-active substrate. Experimentally,
      rapid pyridine vapor detection (within 1 s of exposure) and ultrasensitive 4
      nitrophenol vapor detection (at a sub-ppb level) were successfully achieved in
      open air at room temperature. Such an ultrasensitive SERS platform enabled, for
      the first time, the investigation of both pyridine and 4-nitrophenol vapor
      adsorption isotherms at very low concentrations. Type I and type V behaviors of
      the International Union of Pure and Applied Chemistry isotherm were well
      observed, respectively.

PMID- 22413934
TI  - Chromosome 22q11.2 microdeletion in monozygotic twins with discordant phenotype
      and deletion size.
AB  - We report on a pair of male monozygotic twins with 22q11.2 microdeletion,
      discordant phenotype and discordant deletion size. The second twin had findings
      suggestive of DiGeorge syndrome, while the first twin had milder anomalies
      without any cardiac malformation. The second twin had presented with intractable
      convulsion, cyanosis and cardiovascular failure in the fourth week of life and
      expired on the sixth week of life, whereas the first twin had some characteristic
      facial appearance with developmental delay but no other signs of the 22q11.2
      microdeletion syndrome including cardiovascular malformation. The fluorescence in
      situ hybridization (FISH) analysis had shown a microdeletion on the chromosome
      22q11.2 in both twins. The interphase FISH did not find any evidence for the
      mosaicism. The genomic DNA microarray analysis, using HumanCytoSNP-12 BeadChip
      (Illumina), was identical between the twins except different size of deletion of
      22q11.2. The zygosity using HumanCytoSNP-12 BeadChip (Illumina) microarray
      analysis suggested monozygosity. This observation indicates that altered size of
      the deletion may be the underlying etiology for the discordance in phenotype in
      monozygotic twins. We think early post zygotic events (mitotic non-allelic
      homologous recombination) could have been played a role in the alteration of
      22q11.2 deletion size and, thus phenotypic variability in the monozygotic twins.

PMID- 22413935
TI  - Total synthesis of lepadiformine alkaloids using N-Boc alpha-amino nitriles as
      trianion synthons.
AB  - Lepadiformine A, B, and C were synthesized in an enantiomerically pure form using
      a reductive cyclization strategy. N-Boc alpha-amino nitriles were deprotonated
      and alkylated with enantiomerically pure dibromides to afford the first ring. The
      products were manipulated to introduce phosphate leaving groups, and subsequent
      reductive lithiation followed by intramolecular alkylation formed the second ring
      with high stereoselectivity. The third ring was formed by intramolecular
      displacement of a mesylate by the deprotected amine. Lepadiformine A and B
      contain a hydroxymethyl group adjacent to the amine. This appendage was
      introduced in a sequence using a Polonovski-Potier reaction as the key step. The
      synthetic strategy is stereoselective and convergent and demonstrates the utility
      of N-Boc alpha-amino nitriles as linchpins for alkaloid synthesis.

PMID- 22413936
TI  - Endometrial stromal sarcoma arising from endometriosis of the terminal ileum: the
      role of immunohistochemistry in the differential diagnosis.
AB  - Low-grade endometrial stromal sarcoma (LESS) is an uncommon uterine malignancy.
      Occasionally, it may develop in extrauterine endometriotic lesions and present
      morphological characteristics mimicking various neoplasms, making its diagnosis
      very challenging. We report a rare case of a 56-year-old woman presenting with a
      pelvic mass, initially presumed to be of ovarian origin. After surgical excision
      the diagnosis of a LESS arising from foci of endometriosis of the terminal ileum
      was established. Pelvic lymph nodes and omentum were also infiltrated. The
      patient received adjuvant chemotherapy and medroxyprogesterone; she is alive with
      no evidence of disease after a follow-up of 38 months. Immunohistochemical
      characteristics of the tumor are very important for the differential diagnosis of
      this rare neoplasm and include diffuse strong positivity for CD 10, estrogen
      receptor expression and CD 34 negativity.

PMID- 22413937
TI  - Small-interfering RNA (siRNA)-based functional micro- and nanostructures for
      efficient and selective gene silencing.
AB  - Because of RNA's ability to encode structure and functional information,
      researchers have fabricated diverse geometric structures from this polymer at the
      micro- and nanoscale. With their tunable structures, rigidity, and
      biocompatibility, novel two-dimensional and three-dimensional RNA structures can
      serve as a fundamental platform for biomedical applications, including engineered
      tissues, biosensors, and drug delivery vehicles. The discovery of the potential
      of small-interfering RNA (siRNA) has underscored the applications of RNA-based
      micro- and nanostructures in medicine. Small-interfering RNA (siRNA), synthetic
      double-stranded RNA consisting of approximately 21 base pairs, suppresses
      problematic target genes in a sequence-specific manner via inherent RNA
      interference (RNAi) processing. As a result, siRNA offers a potential strategy
      for treatment of many human diseases. However, due to inefficient delivery to
      cells and off-target effects, the clinical application of therapeutic siRNA has
      been very challenging. To address these issues, researchers have studied a
      variety of nanocarrier systems for siRNA delivery. In this Account, we describe
      several strategies for efficient siRNA delivery and selective gene silencing. We
      took advantage of facile chemical conjugation and complementary hybridization to
      design novel siRNA-based micro- and nanostructures. Using chemical crosslinkers
      and hydrophobic/hydrophilic polymers at the end of siRNA, we produced various RNA
      based structures, including siRNA block copolymers, micelles, linear siRNA
      homopolymers, and microhydrogels. Because of their increased charge density and
      flexibility compared with conventional siRNA, these micro- and nanostructures can
      form polyelectrolyte complexes with poorly charged and biocompatible cationic
      carriers that are both more condensed and more homogenous than the complexes
      formed in other carrier systems. In addition, the fabricated siRNA-based
      structures are linked by cleavable disulfide bonds for facile generation of
      original siRNA in the cytosol and for target-specific gene silencing. These newly
      developed siRNA-based structures greatly enhance intracellular uptake and gene
      silencing both in vitro and in vivo, making them promising biomaterials for siRNA
      therapeutics.

PMID- 22413938
TI  - Pooled week 96 results of the phase III DUET-1 and DUET-2 trials of etravirine:
      further analysis of adverse events and laboratory abnormalities of special
      interest.
AB  - OBJECTIVES: The aim of the study was to investigate the frequency and severity of
      adverse events (AEs) and laboratory abnormalities of interest over 96 weeks of
      treatment with etravirine or placebo in the pooled TMC125 DUET (Demonstrate
      Undetectable viral load in patients Experienced with ARV Therapy) trials.
      METHODS: Treatment-experienced, HIV-1-infected patients randomly received
      etravirine 200 mg twice a day (bid) or placebo, plus a background regimen. The
      frequency and severity of neuropsychiatric, rash, hepatic and lipid AEs were
      analysed; frequencies were also adjusted for total patient-years of exposure
      (PYE). RESULTS: A total of 599 and 604 patients received etravirine and placebo,
      respectively (median treatment duration 96.0 and 69.6 weeks, respectively). There
      was no significant difference between the treatment groups in the frequency of
      neuropsychiatric AEs. However, a significant difference in the frequency of rash
      was observed (20.5% vs. 11.8%, respectively; P < 0.0001); rash was generally mild
      to moderate in severity; the rate of discontinuation because of rash was low
      (2.2% vs. 0% in the etravirine and placebo groups, respectively). The frequency
      of hepatic AEs was low and similar between the treatment groups (8.7% vs. 7.1%,
      respectively; P = 0.3370); hepatic enzyme levels did not increase over time.
      Lipid-related laboratory abnormalities and changes over time in lipid levels were
      generally comparable between treatment groups. Adjusting for treatment exposure,
      the frequency of AEs remained similar between treatment groups, with the
      exception of rash [13.7 vs. 9.3 per 100 PYE; relative risk (95% confidence
      interval) 1.48 (1.02-1.95)]. CONCLUSIONS: The frequency of AEs of interest was
      generally similar between the treatment groups, both overall and when adjusted
      for treatment exposure, with the exception of rash which was more frequent in the
      etravirine group.

PMID- 22413939
TI  - MRI features of gliomatosis cerebri in a dog.
AB  - The features of gliomatosis cerebri involving the brainstem and cerebellum in a 3
      year-old dog are described. In magnetic resonance (MR) images, there was diffuse
      loss of the cerebellar folia and cerebellar gray and white matter contrast.
      Multiple illdefined T2-hyperintensities were present in the cerebellar
      parenchyma. A poorly defined, T2-hyperintense mass effect was present ventral to
      the pons and rostral medulla. No contrast enhancement was noted. Cerebrospinal
      fluid (CSF) was normal. Postmortem examination was consistent with gliomatosis
      cerebri, based on compatible histopathology and immunohistochemical findings.
      Although rare, gliomatosis cerebri should be included as a differential for
      diffuse infiltrative central nervous system (CNS) lesions.

PMID- 22413940
TI  - Unacylated Ghrelin is associated with the isolated low HDL-cholesterol obese
      phenotype independently of insulin resistance and CRP level.
AB  - BACKGROUND: Low plasma high-density lipoprotein-cholesterol (HDL-c) level is
      commonly present in obesity and represents an independent cardiovascular risk
      factor. However, obese patients are a very heterogeneous population and the
      factors and mechanisms that contribute to low HDL-c remain unclear. The aim of
      this study was to investigate the association between plasma HDL-c levels and
      plasma hormonal profiles (insulin, adiponectin, resistin, leptin and ghrelin) in
      subsets of class II and III obese patients. METHODS: Fasting plasma levels of
      glucose, total cholesterol, LDL-c, HDL-c, triglycerides, free fatty acids,
      apoproteins A-I, B-100, B-48, C-II, C-III, insulin, hs-CRP, adipocytokines
      (adiponectin, resistin, leptin), unacylated ghrelin, body composition (DXA) and
      resting energy expenditure were measured in three subsets of obese patients: 17
      metabolically abnormal obese (MAO) with metabolic syndrome and the typical
      metabolic dyslipidaemia, 21 metabolically healthy obese (MHO) without metabolic
      syndrome and with a normal lipid profile, and 21 isolated low HDL-c obese
      patients (LHO) without metabolic syndrome, compared to 21 healthy lean control
      subjects. RESULTS: Insulin resistance (HOMA-IR) increased gradually from MHO to
      LHO and from LHO to MAO patients (p < 0.05 between MHO and MAO and between LHO
      and MAO). In multiple regression analysis, serum unacylated ghrelin levels were
      only positively and independently associated with HDL-c levels in the LHO group
      (p = 0.032). CONCLUSIONS: These results suggest that, in class II and III obese
      patients with an isolated low HDL-c phenotype, unacylated ghrelin is positively
      associated with HDL-c level independently of insulin resistance and CRP levels,
      and may contribute to the highly prevalent low HDL-c level seen in obesity.

PMID- 22413941
TI  - Development of a ReaxFF reactive force field for ettringite and study of its
      mechanical failure modes from reactive dynamics simulations.
AB  - Ettringite is a hexacalcium aluminate trisulfate hydrate mineral that forms
      during Portland cement hydration. Its presence plays an important role in
      controlling the setting rate of the highly reactive aluminate phases in cement
      paste and has also been associated with severe cracking in cured hardened cement.
      To understand how it forms and how its properties influence those of hardened
      cement and concrete, we have developed a first-principles-based ReaxFF reactive
      force field for Ca/Al/H/O/S. Here, we report on the development of this ReaxFF
      force field and on its validation and application using reactive molecular
      dynamics (RMD) simulations to characterize and understand the elastic, plastic,
      and failure response of ettringite at the atomic scale. The ReaxFF force field
      was validated by comparing the lattice parameters, pairwise distribution
      functions, and elastic constants of an ettringite crystal model obtained from RMD
      simulations with those from experiments. The predicted results are in close
      agreement with published experimental data. To characterize the atomistic failure
      modes of ettringite, we performed stress-strain simulations to find that Ca-O
      bonds are responsible for failure of the calcium sulfate and tricalcium aluminate
      (C3A) column in ettringite during uniaxial compression and tension and that
      hydrogen bond re-formation during compression induces an increase in plastic
      strain beyond the material's stress-strain proportionality limit. These results
      provide essential insight into understanding the mechanistic role of this mineral
      in cement and concrete degradation, and the ReaxFF potential developed in this
      work serves as a fundamental tool to further study the kinetics of hydration in
      cement and concrete.

PMID- 22413942
TI  - Histological and immunohistochemical analyses of the chronology of healing
      process after immediate tooth replantation in incisor rat teeth.
AB  - Dental tissues have special characteristics, and its regenerative capacity is
      noteworthy. However, understanding the circumstances that lead to regeneration is
      challenging. In this study, the chronology of the healing process after immediate
      replantation of rat incisor teeth was examined by histological and
      immunohistochemical analyses within a 60-day period. Thirty-six male Wistar rats
      had their maxillary right incisors extracted and replanted after 15 min in saline
      storage. The rats were sacrificed immediately 3, 7, 15, 28, and 60 days after
      replantation. The histological analysis showed rupture of the periodontal
      ligament and formation of a blood clot, which started being replaced by a
      connective tissue after 3 days. At 7 days, the gingival mucosa epithelium was
      reinserted and areas of root resorption could be seen. At 15 days, the
      periodontal ligament was repaired. At 3 days, the pulp presented an absence of
      the odontoblast layer, which started being replaced by a connective tissue. This
      tissue suffered gradual calcification, filling the root canal at 28 and 60 days.
      The root ends were closed. The immunohistochemical analysis revealed greater
      expression of OP, OPG, and RANK proteins in the initial periods (0 and 3 days),
      while TRAP expression predominated at 28 and 60 days (P < 0.05). In conclusion,
      in delayed tooth replantation, there is great new bone formation activity in the
      earlier periods of the repair process, while a predominance of bone resorption
      and remodeling is observed in the more advanced periods.

PMID- 22413943
TI  - Quantitative trait locus mapping for ethanol teratogenesis in BXD recombinant
      inbred mice.
AB  - BACKGROUND: Individual differences in susceptibility to the detrimental effects
      of prenatal ethanol (EtOH) exposure have been demonstrated. Many factors,
      including genetics, play a role in susceptibility and resistance. We have
      previously shown that C57BL/6J (B6) mice display a number of morphological
      malformations following an acute dose of EtOH in utero, while DBA/2J (D2) mice
      are relatively resistant. Here, we present the results of quantitative trait
      locus (QTL) mapping for EtOH teratogenesis in recombinant inbred strains derived
      from a cross between B6 and D2 (BXD RIs). METHODS: Pregnant dams were intubated
      with either maltose-dextrin or 5.8 g/kg EtOH on day 9 of gestation (GD9). On GD
      18, dams were sacrificed and fetuses and placentae were removed. Placentae and
      fetuses were weighed; fetuses were sexed and examined for gross morphological
      malformations. Fetuses were then either placed in Bouin's fixative for subsequent
      soft-tissue analyses or eviscerated and placed in EtOH for subsequent skeletal
      examinations. QTL mapping for maternal weight gain (MWG), prenatal mortality,
      fetal weight (FW) at c-section, placental weight (PW), and several morphological
      malformations was performed using WebQTL. RESULTS: Heritability for our traits
      ranged from 0.06 for PW to 0.39 for MWG. We found suggestive QTLs mediating all
      phenotypes and significant QTLs for FW and digit and rib malformations. While
      most QTL regions are large, several intriguing candidate genes emerged based on
      polymorphisms between B6 and D2 and gene function. CONCLUSIONS: In this first
      mapping study for EtOH teratogenesis, several QTLs were identified. Future
      studies will further characterize these regions. Identification of genes and
      epigenetic modifications mediating susceptibility to the teratogenic effects of
      alcohol in mice will provide targets to examine in human populations.

PMID- 22413944
TI  - Successful treatment of moderate to severe plaque psoriasis with the PEGylated
      Fab' certolizumab pegol: results of a phase II randomized, placebo-controlled
      trial with a re-treatment extension.
AB  - BACKGROUND: Certolizumab pegol (CZP) is a PEGylated antitumour necrosis factor
      agent. OBJECTIVES: To evaluate the efficacy and safety of CZP in patients with
      plaque psoriasis. METHODS: In a randomized, placebo-controlled, double-blind
      study, 176 patients with moderate to severe psoriasis received placebo or CZP 400
      mg at week 0 followed by placebo or CZP (200 or 400 mg) every other week until
      week 10. Co-primary endpoints were >= 75% improvement from baseline in Psoriasis
      Area and Severity Index (PASI 75) and a Physician's Global Assessment (PGA) of
      clear-almost clear at week 12. A re-treatment extension study was conducted in 71
      CZP PASI 75 responders who relapsed during a 12- to 24-week observation period
      without treatment. RESULTS: PASI 75 was achieved by 44/59 (75%), 48/58 (83%) and
      4/59 (7%) patients in the CZP 200 mg, CZP 400 mg and placebo groups, respectively
      (P < 0.001 for both treatment arms vs. placebo). A PGA score of clear-almost
      clear was achieved by 53%, 72% and 2%, respectively (P < 0.001 for both treatment
      arms vs. placebo). In the re-treatment study median PASI scores were similar at
      week 12 in the first treatment and re-treatment periods for both CZP groups.
      Serious adverse events occurred in 3%, 5% and 2% of CZP 200 mg, CZP 400 mg and
      placebo patients, respectively. CONCLUSIONS: Treatment with CZP significantly
      improved psoriasis at week 12. Similar efficacy was observed at week 12 in
      patients receiving re-treatment for loss of response after drug withdrawal.

PMID- 22413945
TI  - Congenital hyperinsulinism and cardiomyopathy.

PMID- 22413946
TI  - Survival estimates for elite male and female Olympic athletes and tennis
      championship competitors.
AB  - In this paper, we report survival estimates for male and female Olympic medal
      winners and for male and female finalists at the British and U S national tennis
      championships. We find a consistent longevity advantage of Olympic medal-winning
      female athletes over Olympic medal-winning male athletes competing separately in
      the same events since 1900 and for female finalists over male finalists competing
      separately in the finals of the national tennis championships of Britain and of
      the United States since the 1880s. This is the case for sample mean comparisons,
      for Kaplan-Meier survival function estimates, including life expectancy, and for
      Cox proportional hazard estimates, which show statistically significant lower
      hazard rates for women with birth year and other variables constant. The female
      longevity advantage over males is similar in the early period samples (birth
      years before 1920) and in the full period samples, and is 5-7 years.

PMID- 22413947
TI  - Inhibitory effects of silver ions on Legionella pneumophila grown on agar,
      intracellular in Acanthamoeba castellanii and in artificial biofilms.
AB  - AIMS: We undertook a series of experiments to investigate the susceptibility of
      Legionella pneumophila grown under extracellular and intracellular conditions and
      other water-related bacteria to silver ions. METHODS AND RESULTS: In this study,
      the antimicrobial effect of silver ions to intra- and extra-cellular grown
      Legionella bacteria was investigated. The minimal inhibitory concentration (MIC)
      after 24 h exposure, leading to a 5 log reduction, was c. 64 MUg l(-1) AgNO(3)
      for extracellular grown Legionella and other tested Gram-positive and Gram
      negative bacteria. In contrast, the MIC for intracellularly grown Legionella was
      up to 4096 MUg l(-1) AgNO(3) after 24 h. Furthermore, the heterotrophic bacteria
      grown within a biofilm model were killed at a concentration of 4-16 MUg l(-1)
      AgNO(3). In contrast, biofilm-associated Legionella were less sensitive (MIC 128
      512 MUg l(-1) AgNO(3)). CONCLUSION: Intracellularly and biofilm-grown legionellae
      are less sensitive against silver compared with agar-grown bacteria. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The reduced sensitivity of Legionella grown in amoebae
      might explain why the effect of silver decontamination requires an extended
      exposure in field trials.

PMID- 22413950
TI  - Biomarker models as surrogates for the disposition index in the Insulin
      Resistance Atherosclerosis Study.
AB  - AIMS: Insulin sensitivity and acute insulin response measure key components of
      Type 2 diabetes aetiology that contribute independently to risk in the Insulin
      Resistance Atherosclerosis Study. As insulin sensitivity and acute insulin
      response are not routinely measured in a clinical setting, we evaluated three
      fasting biomarker models, homeostasis model assessment of insulin sensitivity
      (HOMA-%S), beta-cell function (HOMA-%B) and a Diabetes Risk Score, as potential
      surrogates for risk associated with insulin sensitivity, acute insulin response
      and the interaction of these two measures, the disposition index. METHODS: Models
      were calculated from baseline plasma biomarker concentrations for 664
      participants who underwent a frequently sampled intravenous glucose tolerance
      test. To assess relationships among biomarker models and test measures, we
      calculated improvement in risk estimation gained by combining each fasting
      measure with each frequently sampled intravenous glucose tolerance test measure
      using logistic regression. RESULTS: The strongest correlates of acute insulin
      response, insulin sensitivity and disposition index were HOMA-%B (r(s)(2) =
      0.23), HOMA-%S (r(s)(2) = 0.48) and Diabetes Risk Score (r(s)(2) = 0.34),
      respectively. Individual areas under the curves for prediction of diabetes were
      0.549 (HOMA-%B), 0.694 (HOMA-%S), 0.700 (insulin sensitivity), 0.714 (acute
      insulin response), 0.756 (Diabetes Risk Score) and 0.817 (disposition index).
      Models combining acute insulin response with Diabetes Risk Score (area under the
      curve 0.798) or HOMA-%S (area under the curve 0.805) nearly equalled disposition
      index, outperforming other individual measures (P < 0.05). Insulin sensitivity
      plus Diabetes Risk Score (area under the curve 0.760) was better than insulin
      sensitivity (P = 0.03), but not better than Diabetes Risk Score alone. HOMA-%S
      plus insulin sensitivity (area under the curve 0.704) was not significantly
      better than either alone. CONCLUSIONS: The Diabetes Risk Score and HOMA-%S were
      excellent surrogates for insulin sensitivity, capturing the predictive power of
      insulin sensitivity. Diabetes Risk Score captured some of the additional
      predictive power of acute insulin response, but the HOMA models did not. No
      fasting model was as predictive as disposition index, but the Diabetes Risk Score
      was the best surrogate.

PMID- 22413951
TI  - Innovative approach to investigating the microstructure of calcified tissues
      using specular reflectance Fourier transform-infrared microspectroscopy and
      discriminant analysis.
AB  - Although bone fracture has become a serious global health issue, current clinical
      assessments of fracture risk based on bone mineral density are unable to
      accurately predict whether an individual is likely to suffer a fracture. There is
      increasing recognition that the chemical structure and composition, or
      microstructure, of mineralized tissues has an important role to play in
      determining the fracture resistance of bone. The objective of this preliminary
      study was to evaluate the use of specular reflectance Fourier transform infrared
      (SR FT-IR) microspectroscopy in conjunction with discriminant analysis as an
      innovative technique for providing future insights into the origins of orthopedic
      abnormalities. The impetus for this approach was that SR FT-IR microspectroscopy
      would offer several advantages over conventional transmission methods. Bone
      samples were obtained from young racehorses at known fracture predilection sites
      and spectra were successfully obtained from calcified cartilage and subchondral
      bone for the first time. By applying discriminant analysis to the spectral data
      set in biologically relevant regions, microstructural differences between groups
      of individuals were found to be related to features associated with both the
      mineral and organic components of the bone. The preliminary findings also suggest
      that differences in bone microstructure may exist between healthy individuals of
      the same age, raising important questions around the normal limits of individual
      variation and whether individuals may be predisposed to later fracture as a
      result of detrimental microstructural changes during early growth and
      development.

PMID- 22413949
TI  - In vitro corrosion of ZEK100 plates in Hank's Balanced Salt Solution.
AB  - BACKGROUND: In recent years magnesium alloys have been intensively investigated
      as potential resorbable materials with appropriate mechanical and corrosion
      properties. Particularly in orthopedic research magnesium is interesting because
      of its mechanical properties close to those of natural bone, the prevention of
      both stress shielding and removal of the implant after surgery. METHODS: ZEK100
      plates were examined in this in vitro study with Hank's Balanced Salt Solution
      under physiological conditions with a constant laminar flow rate. After 14, 28
      and 42 days of immersion the ZEK100 plates were mechanically tested via four
      point bending test. The surfaces of the immersed specimens were characterized by
      SEM, EDX and XRD. RESULTS: The four point bending test displayed an increased
      bending strength after 6 weeks immersion compared to the 2 week group and 4 week
      group. The characterization of the surface revealed the presence of high amounts
      of O, P and Ca on the surface and small Mg content. This indicates the
      precipitation of calcium phosphates with low solubility on the surface of the
      ZEK100 plates. CONCLUSIONS: The results of the present in vitro study indicate
      that ZEK100 is a potential candidate for degradable orthopedic implants. Further
      investigations are needed to examine the degradation behavior.

PMID- 22413952
TI  - Amyotrophic lateral sclerosis: new insights into underlying molecular mechanisms
      and opportunities for therapeutic intervention.
AB  - Recent years have witnessed a renewed interest in the pathogenic mechanisms of
      amyotrophic lateral sclerosis (ALS), a late-onset progressive degeneration of
      motor neurons. The discovery of new genes associated with the familial form of
      the disease, along with a deeper insight into pathways already described for this
      disease, has led scientists to reconsider previous postulates. While protein
      misfolding, mitochondrial dysfunction, oxidative damage, defective axonal
      transport, and excitotoxicity have not been dismissed, they need to be re
      examined as contributors to the onset or progression of ALS in the light of the
      current knowledge that the mutations of proteins involved in RNA processing,
      apparently unrelated to the previous "old partners," are causative of the same
      phenotype. Thus, newly envisaged models and tools may offer unforeseen clues on
      the etiology of this disease and hopefully provide the key to treatment.

PMID- 22413953
TI  - Targeting angiogenesis for the treatment of prostate cancer.
AB  - INTRODUCTION: While multiple therapies exist that prolong the lives of men with
      advanced prostate cancer, none are curative. This had led to a search to uncover
      novel targets for prostate cancer therapy, distinct from those of traditional
      hormonal approaches, chemotherapies, immunotherapies and bone-targeting
      approaches. The process of tumor angiogenesis is one target that is being
      exploited for therapeutic gain. AREAS COVERED: The most promising anti-angiogenic
      approaches for treatment of prostate cancer, focusing on clinical development of
      selected agents. These include VEGF-directed therapies, tyrosine kinase
      inhibitors, tumor-vascular disrupting agents, immunomodulatory drugs and
      miscellaneous anti-angiogenic agents. While none of these drugs have yet entered
      the market for the treatment of prostate cancer, several are now being tested in
      Phase III registrational trials. EXPERT OPINION: The development of anti
      angiogenic agents for prostate cancer has met with several challenges. This
      includes discordance between traditional prostate-specific antigen responses and
      clinical responses, which have clouded clinical trial design and interpretation,
      potential inadequate exposure to anti-angiogenic therapies with premature
      discontinuation of study drugs and the development of resistance to anti
      angiogenic monotherapies. These barriers will hopefully be overcome with the
      advent of more potent agents, the use of dual angiogenesis inhibition and the
      design of more informative clinical trials.

PMID- 22413954
TI  - A comparison of computed tomography, computed radiography, and film-screen
      radiography for the detection of canine pulmonary nodules.
AB  - Computed tomography (CT) has become more widely available and computed
      radiography (CR) has replaced film-screen radiography for canine thoracic imaging
      in many veterinary practices. There are limited data comparing these modalities
      in a veterinary clinical setting to detect pulmonary nodules. We compared CT, CR,
      and film-screen radiography for detecting the presence, number, and
      characteristics of pulmonary nodules in dogs. Observer performance for a variety
      of experience levels was also evaluated. Twenty-one client-owned dogs with a
      primary neoplastic process underwent CT and CR; nine also received film-screen
      radiographs. Positive/negative classification by consensus agreed between the
      three modalities in 8/9 dogs and between CR and CT in the remaining 12. CT
      detected the greatest (P = 0.002) total number of nodules and no difference was
      seen between CR and films. The greatest number of nodules was seen in the right
      middle and both caudal regions, but only using CT (P < 0.0001). Significantly
      smaller nodules were detected with CT (P = 0.0007) and no difference in minimum
      size was detected between CR and films. Observer accuracy was high for all
      modalities; particularly for CT (90.5-100%) and for the senior radiologist (90.5
      100%). CT was also characterized by the least interobserver variability. Although
      CT, CR, and film-screen performed similarly in determining the presence or
      absence of pulmonary nodules, a greater number of smaller nodules was detected
      with CT, and CT was associated with greater diagnostic confidence and observer
      accuracy and agreement.

PMID- 22413955
TI  - No increased risk of hepatotoxicity in long-term use of nonnucleoside reverse
      transcriptase inhibitors in HIV-infected patients.
AB  - OBJECTIVE: The aim of this study was to assess the incidence of hepatotoxicity in
      patients who had used nonnucleoside reverse transcriptase inhibitors (NNRTIs) for
      at least 3 years. METHODS: The study group consisted of HIV-infected patients
      under follow-up at our clinic, who had continuously used an NNRTI-containing
      regimen (efavirenz or nevirapine) for at least 3 years. Patients who had used
      protease inhibitors (PIs) for the same time span constituted a control group.
      Hepatotoxicity was graded according to the modified AIDS Clinical Trial Group
      grading system, using alanine aminotransferase (ALT) as a marker. RESULTS: One
      hundred and twenty-two patients on an NNRTI regimen and 54 PI-using patients were
      included in the analysis. The mean follow-up time was nearly 6 years. Eighteen
      NNRTI-using patients (14.8%) developed a clinically relevant (>=  grade II) event
      of hepatotoxicity during treatment; five of them (4.1%) developed severe
      hepatotoxicity (>=  grade III). No significant difference in the hepatotoxicity
      rate was seen between NNRTI- and PI-using patients (14.8 vs. 18.5%, respectively;
      P = 0.52) or between patients using efavirenz and nevirapine (13.8% vs. 16.7%,
      respectively; P = 0.51). A hepatitis C virus (HCV) coinfection was associated
      with an increased risk of the development of hepatotoxicity during NNRTI therapy
      [odds ratio (OR) 1.83; 95% confidence interval (CI) 1.33-4.24; P < 0.01].
      Finally, we observed that more hepatotoxic events occurred during the first year
      of NNRTI therapy compared with the entire period after 1 year (6.6 vs. 2.8
      events, respectively, per 100 person-years of treatment; P = 0.04). CONCLUSIONS:
      Long-term NNRTI use was not associated with a higher risk of clinically
      significant liver toxicity in patients who had been treated with NNRTI for at
      least 3 years.

PMID- 22413956
TI  - Pathogen safety of human C1 esterase inhibitor concentrate.
AB  - BACKGROUND: Human plasma-derived products--such as C1 esterase inhibitor (C1-INH)
      concentrate, used to treat hereditary angioedema--carry with them the risk of
      transmitting blood-borne viruses and, theoretically, prion proteins. To minimize
      this risk, three complementary approaches are implemented: selection and testing
      of plasma donations for the absence of pathogenic blood-borne viruses, similarly
      testing and releasing the plasma pool for fractionation, and ensuring that the
      manufacturing process includes validated steps for pathogen inactivation and
      removal. STUDY DESIGN AND METHODS: This article describes the selection of plasma
      for the production of C1-INH and the studies used to confirm the pathogen
      reduction capacity of the manufacturing process: three independent virus
      reduction steps--pasteurization, hydrophobic interaction chromatography (HIC),
      and virus filtration--and two prion reduction steps. Samples of product
      intermediates from the manufacturing steps were spiked with a panel of enveloped
      and nonenveloped viruses and two prion preparations and subjected to a valid
      scaled-down version of the respective manufacturing steps resulting in the
      quantification of the pathogen reduction factors. RESULTS: Validation studies
      demonstrated overall virus reduction factors for all viruses of more than 15 log,
      considerably exceeding the potential amount of virus present in a plasma pool for
      fractionation. Prion proteins were also efficiently removed by the manufacturing
      process, as currently determined in evaluating the prion removal capacity of the
      ammonium sulfate precipitation and HIC steps. CONCLUSION: The pathogen reduction
      capacity demonstrated here indicates that the manufacturing process of the C1-INH
      Berinert is highly effective for reducing enveloped and nonenveloped viruses and
      prion proteins.

PMID- 22413957
TI  - Large parasitic myomas in abdominal subcutaneous adipose tissue along a previous
      myomectomy scar.
AB  - The incidence of iatrogenic parasitic uterine myomas associated with the use of a
      laparoscopic morcellator has been increasing over the past decade. Recently, we
      encountered a very rare case with a large parasitic myoma measuring 12 cm in
      diameter in the abdominal subcutaneous adipose tissue along an abdominal
      longitudinal surgical scar. The patient had twice undergone abdominal myomectomy
      for multiple fundal myomas. This is the first report describing a case with as
      large a parasitic myoma presenting in the suprafascial adipose tissue under the
      surgical scar after laparotomy. In such a case demonstrating a solid tumor of
      unknown cause after a gynecologic surgical procedure, a parasitic myoma must be
      included in the differential diagnosis.

PMID- 22413958
TI  - Multiple fetal anomalies in association with topiramate and oxcarbezepine
      treatment.
AB  - We present a case of a woman who used topiramate (100 mg) and oxcarbazepine (300
      mg) continuously during pregnancy. Multiple fetal anomalies including limp
      defects of the lower extremities, pericardiac fluid collection, cardiomegaly,
      cleft lip and palate, absent right kidney, and dysplastic left kidney were found
      by ultrasonography. Labor was induced and anomalies were confirmed by autopsy.
      The malformation rate after exposure to oxcarbazepine in utero as a monotherapy
      was calculated to be 2.4%, which is compatible with the malformation rate seen in
      the general population. Topiramate is teratogenic in mice, rats, and rabbits, but
      there are very few reports about its teratogenicity in humans.

PMID- 22413959
TI  - Carvedilol attenuates the progression of alcohol fatty liver disease in rats.
AB  - BACKGROUND: Hepatosteatosis is an essential step in liver disease progression.
      However, the mechanisms that mediate the progression of hepatosteatosis and the
      optimal inhibitor of them remain largely unclear. The sympathetic nervous system
      (SNS) is responsible for the lipid metabolism and the accumulation of collagen
      that occurs in an injured liver. Medicines that inhibit this pathway may be a
      relevant treatment for the hepatosteatosis, and then reduce the liver injury that
      progresses through the stage of steatosis to fibrosis. METHODS: Using an ethanol
      liquid-diet-fed rat model of alcohol fatty liver disease (AFLD), we studied the
      effects of carvedilol, which can block the SNS completely via beta1, beta2, and
      alpha1 adrenergic receptors, on the sympathetic tone, hepatosteatosis, and
      fibrosis based on histological, immunohistochemical, Western blot, and reverse
      transcriptase polymerase chain reaction analyses. RESULTS: Carvedilol inhibited
      the ethanol-induced whole-body and hepatic sympathetic activities based on the
      serum 3-methoxy-4-hydroxyphenylglycol level and hepatic tyrosine hydroxylase
      expression. Carvedilol attenuated the hepatosteatosis, as evidenced by reduced
      hepatic triglyceride level and the accumulation of fatty droplets within
      hepatocytes, down-regulated fatty acid synthase and sterol regulatory element
      binding protein-1, and up-regulated peroxisome proliferator-activated receptor
      alpha. No fibrosis signs were shown in our rat model. Carvedilol inhibited
      ethanol-induced the thickening of zone 3 vessel walls, reduced the activation of
      hepatic stellate cells (HSCs), and decreased the induction of collagen,
      transforming growth factor beta1, and tissue inhibitor of metalloproteinases-1.
      Tumor necrosis factor alpha (TNF-alpha) was expressed on the activated HSCs and
      inhibited by carvedilol based on the immunohistochemical double staining
      analysis. CONCLUSIONS: Ethanol metabolism-induced lipogenesis may trigger the SNS
      activated HSCs feedback loop, and then induct the activated HSCs and the
      activated HSCs-derived TNF-alpha, the mediator of lipogenesis, overproduction.
      Carvedilol may block this feedback loop via antisympathetic activity and
      demonstrate its preventive role on the development of hepatosteatosis in rat with
      AFLD.

PMID- 22413960
TI  - Modified routes to the "designer" surfactant PQS.
AB  - Described herein are newly developed, straightforward entries to
      polyethyleneglycol ubiquinol succinate (PQS, n = 2), a designer surfactant that
      serves as precursor to micelle-forming, covalently bound catalysts for a variety
      of transformations in water with in-flask catalyst recycling.

PMID- 22413961
TI  - Functional analyses of the mutation nt-128 T->G in the hepatocyte nuclear factor
      1alpha promoter region in Chinese diabetes pedigrees.
AB  - AIMS: Hepatocyte nuclear factor-1alpha (HNF-1alpha) regulates the expression of
      genes encoding proteins involved in glucose metabolism and insulin secretion.
      Mutations in the HNF-1alpha gene cause maturity-onset diabetes of the young Type
      3. However, the mechanism leading to this disease has not been completely
      ascertained. Previously, we found a novel mutation in the regulatory element of
      the human HNF-1alpha gene in two Chinese diabetes pedigrees. The nucleotide at
      position -128 T was substituted by G (nt-128 T->G). In this study, we analysed
      the functional defect of nt-128 T->G in HNF-1alpha transcription activity.
      METHODS: Luciferase reporter gene assays were carried out to examine the
      functional characteristics of this mutant. Electrophoretic mobility shift assays
      and chromatin immunoprecipitation were performed to confirm the binding of
      nuclear proteins to oligonucleotides. RESULTS: The variant construct (nt-128 T
      >G) had a 1.65-fold increase in promoter activity compared with that of the wild
      type construct in HepG2 cells and a 1.33-fold increase in MIN6 cells,
      respectively. The variant resided at a FOXA/HNF-3 binding site identified by a
      series of competitive electrophoretic mobility shift assays and antibody
      supershift analyses. The assays showed a differential binding affinity in the
      wild-type and the nt-128 T->G mutant fragments by FOXA/HNF-3. Chromatin
      immunoprecipitation indicated that FOXA/HNF-3 bound to this region in vivo. One
      nucleotide substitution in the FOXA/HNF-3 site in the human HNF-1alpha regulatory
      element caused an increase of HNF-1alpha transcriptional activity. CONCLUSIONS:
      Our data suggested that this substitution in the promoter region affects DNA
      protein interaction and HNF-1alpha gene transcription. The mutant may contribute
      to the development of diabetes in these two nt-128 T->G pedigrees of Chinese.

PMID- 22413962
TI  - Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2
      diabetes, a randomised controlled trial.
AB  - BACKGROUND: Combining metformin (XR) with dapagliflozin to initiate
      pharmacotherapy in patients with type 2 diabetes (T2D) and high baseline HbA1c
      may be advantageous. We conducted two randomised, double-blind, three-arm 24-week
      trials in treatment-naive patients to compare dapagliflozin plus metformin,
      dapagliflozin alone and metformin alone. METHODS: Eligible patients had baseline
      HbA1c 7.5-12%. Each trial had three arms: dapagliflozin plus metformin,
      dapagliflozin monotherapy and metformin monotherapy. Dapagliflozin in combination
      and as monotherapy was dosed at 5 mg (Study 1) and 10 mg (Study 2). Metformin in
      combination and as monotherapy was titrated to 2000 mg. The primary endpoint was
      HbA1c change from baseline; secondary endpoints included change in fasting plasma
      glucose (FPG) and weight. RESULTS: In both trials, combination therapy led to
      significantly greater reductions in HbA1c compared with either monotherapy: -2.05
      for dapagliflozin + metformin, -1.19 for dapagliflozin, and -1.35 for metformin
      (p < 0.0001) (Study 1); -1.98 for dapagliflozin + metformin, -1.45 for
      dapagliflozin and -1.44 for metformin (p < 0.0001) (Study 2). Combination therapy
      was statistically superior to monotherapy in reduction of FPG (p < 0.0001 for
      both studies); combination therapy was more effective than metformin for weight
      reduction (p < 0.0001). Dapagliflozin 10 mg was non-inferior to metformin in
      reducing HbA1c (Study 2). Events suggestive of genital infection were reported in
      6.7%, 6.9% and 2.0% (Study 1) and 8.5%, 12.8% and 2.4% (Study 2) of patients in
      combination, dapagliflozin and metformin groups; events suggestive of urinary
      tract infection were reported in 7.7%, 7.9% and 7.5% (Study 1) and 7.6%, 11.0%
      and 4.3% (Study 2) of patients in the respective groups. No major hypoglycaemia
      was reported. CONCLUSION: In treatment-naive patients with T2D, dapagliflozin
      plus metformin was generally well tolerated and effective in reducing HbA1c, FPG
      and weight. Dapagliflozin-induced glucosuria led to an increase in events
      suggestive of urinary tract and genital infections.

PMID- 22413963
TI  - Genomic SNP array as a gold standard for prenatal diagnosis of foetal ultrasound
      abnormalities.
AB  - BACKGROUND: We have investigated whether replacing conventional karyotyping by
      SNP array analysis in cases of foetal ultrasound abnormalities would increase the
      diagnostic yield and speed of prenatal diagnosis in clinical practice.
      FINDINGS/RESULTS: From May 2009 till June 2011 we performed HumanCytoSNP-12 array
      (HCS) (http://www.Illumina.com) analysis in 207 cases of foetal structural
      abnormalities. HCS allows detecting unbalanced genomic abnormalities with a
      resolution of about 150/200 kb. All cases were selected by a clinical geneticist
      after excluding the most common aneuploidies by RAD (rapid aneuploidy detection).
      Pre-test genetic counselling was offered in all cases.In 24/207 (11,6%) foetuses
      a clinically relevant genetic abnormality was detected. Only 8/24 abnormalities
      would have been detected if only routine karyotyping was performed.
      Submicroscopic abnormalities were found in 16/207 (7,7%) cases. The array results
      were achieved within 1-2 weeks after amniocentesis. CONCLUSIONS: Prenatal SNP
      array testing is faster than karyotyping and allows detecting much smaller
      aberrations (~0.15 Mb) in addition to the microscopic unbalanced chromosome
      abnormalities detectable with karyotyping (~ > 5 Mb). Since karyotyping would
      have missed 66% (16/24) of genomic abnormalities in our cohort, we propose to
      perform genomic high resolution array testing assisted by pre-test counselling as
      a primary prenatal diagnostic test in cases of foetal ultrasound abnormalities.

PMID- 22413964
TI  - Smoking and prevalence of allergic disorders in Japanese pregnant women: baseline
      data from the Kyushu Okinawa Maternal and Child Health Study.
AB  - BACKGROUND: Studies on the associations between smoking and allergic diseases
      have mostly focused on asthma. Epidemiological studies in adults on the effects
      of smoking on allergic diseases other than asthma, such as eczema and
      rhinoconjunctivitis, have been limited, and the information that is available has
      been inconsistent. The aim of this study was to investigate the association
      between smoking status and environmental tobacco smoke (ETS) exposure and the
      prevalence of allergic diseases. METHODS: Study subjects were 1743 pregnant
      Japanese women. The definitions of wheeze and asthma were based on criteria from
      the European Community Respiratory Health Survey whereas those of eczema and
      rhinoconjunctivitis were based on criteria from the International Study of Asthma
      and Allergies in Childhood. Adjustment was made for age; region of residence;
      family history of asthma, atopic eczema, and allergic rhinitis; household income;
      and education. RESULTS: Compared with never smoking, current smoking and >= 4
      pack-years of smoking were independently positively associated with the
      prevalence of wheeze. There were no associations between smoking status and the
      prevalence of asthma, eczema, or rhinoconjunctivitis. When subjects who had never
      smoked were classified into four categories based on the source of ETS exposure
      (never, only at home, only at work, and both), exposure occurring both at home
      and at work was independently associated with an increased prevalence of two
      outcomes: wheeze and rhinoconjunctivitis. No relationships were observed between
      exposure to ETS and the prevalence of asthma or eczema. CONCLUSIONS: Our results
      provide evidence that current smoking and ETS exposure may increase the
      likelihood of wheeze. The possibility of a positive association between ETS
      exposure and rhinoconjunctivitis was also suggested.

PMID- 22413965
TI  - Accuracy of computed tomography in determining lesion size in canine appendicular
      osteosarcoma.
AB  - Multidetector contrast enhanced computed tomography with acquisition of 0.625-mm
      thick transverse images was used to measure the extent of appendicular
      osteosarcoma in 10 dogs. The measured length of tumor based on CT was compared to
      the true length of tumor using histopathology. There was a statistically
      significant association with good correlation between the true length of
      osteosarcoma compared to the length of intramedullary/endosteal abnormalities on
      CT with a mean overestimation of 1.8% (SD = 15%). There was not a statistically
      significant association between the true tumor length and the length of
      periosteal proliferation on CT with a mean overestimation of 9.7% (SD = 30.3%).
      There was a statistically significant association, but with poor correlation,
      between the true tumor length compared to the length of abnormal contrast
      enhancement with a mean overestimation of 9.6% (SD = 34.8%). The extent of
      intramedullary/endosteal CT abnormalities assessed from submillimeter transverse
      images may be of value in assessing patient candidacy and surgical margins for
      limb-sparing surgery.

PMID- 22413966
TI  - Reflectance mode confocal microscopy and digital image analysis in naevus of Hori
      and pathogenetic evaluation.

PMID- 22413967
TI  - Relative risk of cardiovascular disease among people living with HIV: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: The aim of this study was to estimate the relative risk of
      cardiovascular disease (CVD) among people living with HIV (PLHIV) compared with
      the HIV-uninfected population. METHODS: We conducted a systematic review and meta
      analysis of studies from the peer-reviewed literature. We searched the Medline
      database for relevant journal articles published before August 2010. Eligible
      studies were observational and randomized controlled trials, reporting CVD,
      defined as myocardial infarction (MI), ischaemic heart disease, cardiovascular
      and cerebrovascular events or coronary heart disease among HIV-positive adults.
      Pooled relative risks were calculated for various groupings, including different
      classes of antiretroviral therapy (ART). RESULTS: The relative risk of CVD was
      1.61 [95% confidence interval (CI) 1.43-1.81] among PLHIV without ART compared
      with HIV-uninfected people. The relative risk of CVD was 2.00 (95% CI 1.70-2.37)
      among PLHIV on ART compared with HIV-uninfected people and 1.52 (95% CI 1.35
      1.70) compared with treatment-naive PLHIV. We estimate the relative risk of CVD
      associated with protease inhibitor (PI)-, nucleoside reverse transcriptase
      inhibitor- and nonnucleoside reverse transcriptase inhibitor-based ART to be 1.11
      (95% CI 1.05-1.17), 1.05 (95% CI 1.01-1.10) and 1.04 (95% CI 0.99-1.09) per year
      of exposure, respectively. Not all ART was associated with increased risk;
      specifically, lopinavir/ritonavir and abacavir were associated with the greater
      risk and the relative risk of MI for PI-based versus non-PI-based ART was 1.41
      (95% CI 1.20-1.65). CONCLUSION: PLHIV are at increased risk of cardiovascular
      disease. Although effective in prolonging survival, ART (in particular PI-based
      regimens) is related to further increased risk of CVD events among people at
      highest initial absolute risk of cardiovascular disease.

PMID- 22413968
TI  - Patient blood transfusion management: discharge hemoglobin level as a surrogate
      marker for red blood cell utilization appropriateness.
AB  - BACKGROUND: Blood transfusion management strategies minimize transfusion
      associated risks, enhance outcomes, and reduce costs. We explored an association
      of discharge hemoglobin (Hb) with pretransfusion Hb, transfusion indications, and
      red blood cell (RBC) transfusions. We stipulate that patients with discharge Hb
      concentrations greater than 10.0 g/dL, or even 9.0 g/dL, received excessive RBC
      transfusions. STUDY DESIGN AND METHODS: We examined aggregate data from five
      hospitals and for one of the hospitals, the focus hospital, we reviewed patient
      records for a period of 6 months. Data analyses included number of RBC units
      transfused and Hb values before transfusion, after transfusion, and at discharge.
      RESULTS: In aggregate, 27% to 47% patients had discharge Hb levels greater than
      10.0 g/dL. At the focus hospital, 27% had a discharge Hb level greater than 10
      g/dL and 50.3% had a discharge Hb level greater than 9.0 g/dL. At the focus
      hospital, the mean Hb trigger for transfusion was a Hb level of 7.3 g/dL; the
      mean posttransfusion Hb level was 9.3 g/dL and mean discharge Hb level was 9.2
      g/dL. Overall, 76% of the transfusions were of an even number of RBC units.
      CONCLUSION: In aggregate, overutilization exceeded 20%. At the focus hospital,
      approximately one-quarter of patients receiving transfusions had a Hb
      concentration greater than 10.0 g/dL at discharge. Transfused patients' discharge
      Hb concentration represents an effective indicator for retrospective monitoring
      of transfusion appropriateness. In light of the large number of patients
      receiving even number transfusions, reviewing Hb levels after transfusion of each
      RBC unit could reduce unnecessary transfusions. Retrospective review of discharge
      Hb data focuses providers on transfusion outcomes and affords an educational
      opportunity for blood utilization management.

PMID- 22413969
TI  - Editorial: lipids in cancer cell biology and therapy.

PMID- 22413970
TI  - Statins and protein prenylation in cancer cell biology and therapy.
AB  - The use of statins has scaled up to become one of the most prescribed medicines
      in the world and have been very useful in the manegement of cardiovascular
      diseases and related mortality. The disclosure of their chemical structure
      similar to that of hydroxy methyl glutaryl-CoA (HMG-CoA) revealed their ability
      to compete with and inhibit the rate-limiting enzyme HMG-CoA reductase that
      catalyzes the synthesis of mevalonate, which then serves as the precursor for
      isoprenoids and cholesterol in the mevalonate pathway. While most of the effects
      of statins are associated with the lowering of cellular cholesterol levels, it is
      clear that they also blunt the non-sterol branch of the mevalonate pathway,
      decreasing formation of isoprenoids and altering protein-prenylation, a critical
      event in the posttranslational modulation of proteins involved in the regulation
      of cell cycle progression, proliferation and signaling pathways. Randomized
      controlled trials for the prevention of cardiovascular diseases indicated that
      statins elicited provocative and unexpected benefits for reducing a number of
      different types of cancers, including colorectal carcinoma, melanoma, prostate
      and hepatocellular carcinoma, although in other cancer types the preclinical
      expectations of statins were dissapointing. In this review, we will describe the
      evidence and mechanisms underlying the potential beneficial use of statins and
      the role of protein prenylation in cancer prevention. Of relevance, the
      combination of statins with other anti cancer drugs may be a significant asset in
      malignancies resistant to current therapy.

PMID- 22413972
TI  - Congenital heart disease.

PMID- 22413971
TI  - Trypsin immobilization on hairy polymer chains hybrid magnetic nanoparticles for
      ultra fast, highly efficient proteome digestion, facile 18O labeling and absolute
      protein quantification.
AB  - In recent years, quantitative proteomic research attracts great attention because
      of the urgent needs in biological and clinical research, such as biomarker
      discovery and verification. Currently, mass spectrometry (MS) based bottom up
      strategy has become the method of choice for proteomic quantification. In this
      strategy, the amount of proteins is determined by quantifying the corresponding
      proteolytic peptides of the proteins, therefore highly efficient and complete
      protein digestion is crucial for achieving accurate quantification results.
      However, the digestion efficiency and completeness obtained using conventional
      free protease digestion is not satisfactory for highly complex proteomic samples.
      In this work, we developed a new type of immobilized trypsin using hairy noncross
      linked polymer chains hybrid magnetic nanoparticle as the matrix aiming at ultra
      fast, highly efficient proteomic digestion and facile (18)O labeling for
      absolution protein quantification. The hybrid nanoparticle is synthesized by in
      situ growth of hairy polymer chains from the magnetic nanoparticle surface using
      surface initiated atom transfer radical polymerization technique. The flexible
      noncross-linked polymer chains not only provide large amount of binding sites but
      also work as scaffolds to support three-dimensional trypsin immobilization which
      leads to increased loading amount and improved accessibility of the immobilized
      trypsin. For complex proteomic samples, obviously increased digestion efficiency
      and completeness was demonstrated by 27.2% and 40.8% increase in the number of
      identified proteins and peptides as well as remarkably reduced undigested
      proteins residues compared with that obtained using conventional free trypsin
      digestion. The successful application in absolute protein quantification of
      enolase from Thermoanaerobacter tengcongensis protein extracts using (18)O
      labeling and MRM strategy further demonstrated the potential of this hybrid
      nanoparticle immobilized trypsin for high throughput proteome quantification.

PMID- 22413973
TI  - Novel imaging techniques for the diagnosis and treatment of congenital heart
      defects: MR-guided interventions and beyond.

PMID- 22413975
TI  - Personalized Medicine in the Genomics Era: highlights from an international
      symposium on childhood heart disease.
AB  - As the population of childhood heart disease survivors grows, a better
      understanding of the genetic underpinnings of heart disease is needed to improve
      diagnostics, therapeutics and outcomes. The Trans-Atlantic Research Network,
      GenomeHeart and The SickKids Heart Centre Biobank hosted an international
      symposium on childhood heart disease titled 'Personalized Medicine in the
      Genomics Era'. Experts in cardiology, developmental biology, genomics,
      pharmacology, bioinformatics, stem cell biology, ethics and biobanking shared
      their knowledge and expertise. The 2-day symposium hosted participants from North
      America, Europe and Asia including scientists, physicians, nurses, trainees and
      representatives from industry partners, federal and provincial funding agencies,
      and patient and community groups. The symposium focused on international research
      partnerships and application of current state-of-the-art in genomics and stem
      cell medicine towards personalized healthcare for childhood onset heart disease.

PMID- 22413976
TI  - Potential for stem cell use in congenital heart disease.
AB  - This article reports on the evolving field of stem cell therapy and its impact on
      the management of cardiac pathology, in particular congenital heart disease. To
      date, stem cell therapy has focused on cardiomyoplasty for heart muscle disease,
      stem cell therapies are already in clinical use for these disorders. Research is
      now also supporting the potential role of stem cell therapy for congenital heart
      disease. In the future it may be possible to use stem cells to create cellular
      grafts and structures that may be surgically implanted into the disordered heart
      using bioengineering technology. Different types of stem cells have been
      evaluated and the identification of specific cardiac stem cells offers great
      potential. Preliminary animal studies investigating fetal cardiac therapies are
      also underway. These new directions for stem cell research provide exciting
      potential for the future management of congenital heart disease.

PMID- 22413977
TI  - Changing epidemiology and mortality in adult congenital heart disease: looking
      into the future.
AB  - Advances in surgical and medical treatment of children born with congenital heart
      disease have led to a growing number of adult survivors, particularly to a
      growing number of adults with complex congenital heart disease. Childhood
      mortality has continuously decreased over the last few decades and mortality has
      shifted almost entirely to adulthood. However, most patients are not cured and
      many remain at risk of premature death. The extent of excess mortality among
      individual congenital disease entities is not well defined. In this article we
      outline the current demographics of adults with selected congenital heart
      lesions. Based on these contemporary patient cohorts, we delineate future changes
      in patient demographics. A better understanding of these trends may help in the
      optimal planning of future resource allocation for medical care and optimal
      planning of multicenter research, for this novel and growing population of young,
      chronically ill adults.

PMID- 22413978
TI  - Neurological injury and anesthetic neurotoxicity following neonatal cardiac
      surgery: does the head rule the heart or the heart rule the head?
AB  - The improvements in care of children with heart disease have resulted in a major
      decrease in mortality and increased attention to adverse events and quality of
      survival. There is important neurological morbidity in children with congenital
      heart disease. Some problems such as stroke or seizure may be immediately
      apparent, but others, such as learning disability and motor delay emerge over
      time. The etiology is multifactorial and includes genetic, procedural and social
      causes. Only some factors are modifiable. Over the last decade, evidence has been
      presented that anesthetic drugs may be a potential cause of CNS morbidity.
      Neonates and infants may be particularly vulnerable to this. The purpose of this
      article is to describe the multiple known causes of neurodevelopmental impairment
      in children with heart disease, including anesthetic agents, and to explore the
      relationship between congenital heart disease and its treatment in this regard.

PMID- 22413979
TI  - Fetal cardiac screening and variation in prenatal detection rates of congenital
      heart disease: why bother with screening at all?
AB  - Antenatal screening for fetal cardiac abnormalities was introduced over 25 years
      ago, yet detection of congenital heart disease before birth remains a challenge.
      While experienced tertiary centers report a high level of diagnostic accuracy,
      with most major forms of congenital heart disease being detectable before birth,
      the overall detection rate remains low. Pregnancies at increased risk of having
      an affected baby are referred to tertiary centers for fetal ECG, but most cases
      of congenital heart disease will occur in low-risk pregnancies. These cases will
      only be detected by screening the low-risk population at the time of routine
      obstetric scanning. Many obstetric ultrasound units have learnt to successfully
      obtain, and correctly interpret, views of the heart, including the four-chamber
      view and outflow tract views. However, standards for doing this are not uniform,
      nationally or internationally, so there is a significant variation in detection
      rates across individual countries and between different countries. Early
      diagnosis of babies with lesions that can result in cardiovascular collapse and
      death, could improve their survival as well as reducing morbidity. In addition,
      detection of a cardiac abnormality during pregnancy allows time to prepare
      parents for the likely course of events after birth. It also facilitates
      detection of other abnormalities in the baby and gives parents a choice, even if
      the choice is difficult and unwelcome. As well as providing parents with accurate
      and up-to-date information regarding the their baby's abnormality, it is vital to
      provide continuing support to help them deal with the problem, regardless of what
      decisions they make. Much work remains to establish a uniform standard for
      antenatal detection of cardiac abnormalities. More recent national guidelines for
      examining the fetal heart along with formalized auditing processes should help to
      achieve this, although considerable time and effort will be required,
      particularly with regard to the teaching and training required.

PMID- 22413980
TI  - Future horizons for catheter-based interventions in adult congenital and
      structural heart disease.
AB  - In recent decades, there has been an exponential growth in both the number and
      range of catheter-based interventions for adult congenital and structural heart
      disease. In this article, we discuss the rationale for the ongoing development of
      minimally invasive multidisciplinary interventions; the required training
      elements necessary to achieve expertise in the field; the cardiac team needed to
      best perform these interventions; and the currently available and up and coming
      technologies for performing transcatheter valve therapies.

PMID- 22413981
TI  - The use of reconstructive surgery to improve quality of life and survival in
      prenatal hypoplastic left heart syndrome.
AB  - Outcomes for hypoplastic left heart syndrome have improved substantially in the
      era of prenatal diagnosis. Current stage 1 survival rates are in excess of 90% in
      the absence of risk factors. However, fetuses with an intact atrial septum
      continue to have poor postnatal survival. Accurate diagnosis of these fetuses
      with an intact atrial septum relies upon careful assessment of the patent foramen
      ovale, pulmonary venous Doppler flow patterns and branch pulmonary artery Doppler
      flow patterns. Prenatal and perinatal interventions, such as the placement of an
      atrial stent in utero or delivery at a center where a stent may be placed
      immediately after birth to relieve left atrial hypertension, may improve survival
      in this particularly high-risk group.

PMID- 22413982
TI  - Single-ventricle palliation for high-risk neonates: examining the feasibility of
      an automated home monitoring system after stage I palliation.
AB  - Strategies to reduce interstage morbidity and mortality for patients with single
      ventricle following stage I palliation include, standardized care protocols,
      focused high-risk outpatient clinics, dedicated teams that focus on the unique
      needs of these fragile patients and use of home surveillance monitoring. Use of
      telemedicine devices for home monitoring has been shown to improve outcomes in
      adults. These devices allow for a more automated approach to home monitoring that
      have many advantages. We describe our program that utilizes a web-based
      telemedicine device to capture and transmit data from the homes of our patients
      during the interstage period. Our early data suggest that home telemedicine is
      feasible, provides a more systematic data review and analysis and supports the
      assertion that patients using home surveillance have significantly better
      nutritional status than those not using home monitoring.

PMID- 22413983
TI  - Stenting the patent ductus arteriosus in duct-dependent pulmonary circulation:
      techniques, complications and follow-up issues.
AB  - Maintaining ductal patency in duct-dependent congenital heart lesions by
      implantation of coronary stents is an alternative to systemic pulmonary shunt in
      selected cases and lesions with suitable anatomy. This article focuses on the
      procedure as the initial palliation in duct-dependent pulmonary circulation, its
      associated pitfalls and complications. A good understanding of the diverse duct
      morphology is paramount prior to stenting of the ductus. Long tortuous duct,
      insufficiently constricted ductus at the pulmonary end and ductus with associated
      branch pulmonary artery stenosis at the site of insertion are not suitable for
      stenting. Durability of palliation is generally inferior to a surgical shunt and
      this may dictate earlier definitive surgical repair. Acceleration of branch
      pulmonary artery stenosis in certain ductal morphology limits its general
      applicability. Bioabsorbable and biodegradable stents may offer some solution to
      this problem.

PMID- 22413984
TI  - Percutaneous interventions of the aorta.
AB  - Coarctation of the aorta includes a wide array of anatomical and
      pathophysiological variations that may cause important long-term morbidity and
      mortality. Percutaneous techniques, such as balloon dilation and stenting, allow
      clinicians to safely decrease or abolish most gradients along the aorta, albeit
      with limitations. Proper patient selection and interventional technique allow
      clinicians to obtain an adequate stretch or therapeutic tear of the vessel wall,
      but should avoid complications, such as an excessive tear, dissection, aneurysm
      formation or rupture. The interventional technique is tailored by patient
      characteristics such as age, size and growth potential, by characteristics of the
      lesion such as degree of narrowing, length, angulation(s) and by local
      regulations.

PMID- 22413985
TI  - Modulation of pulmonary vascular resistance as a target for therapeutic
      interventions in Fontan patients: focus on phosphodiesterase inhibitors.
AB  - Despite advancements in surgical techniques over the past 20 years, Fontan
      patients have decreased exercise capacity as a consequence of an inherent
      inability to adequately increase cardiac output during exercise. They are also
      affected by several complications that are associated with considerable morbidity
      and mortality. As the systemic and pulmonary circulations are placed in series
      without a subpulmonary ventricle propelling blood through the pulmonary
      vasculature, the systemic venous pressure and the respiratory mechanics are the
      only forces driving pulmonary blood flow. In Fontan circulation, pulmonary
      vascular resistance is the single most important factor involved in the
      limitation of cardiac output and treatments able to decrease pulmonary vascular
      resistance might conversely improve cardiac output and exercise capacity. In this
      article we discuss the initial experience with the use of sildenafil in Fontan
      patients and we discuss the possible mechanisms through which sildenafil might
      positively act in Fontan circulation.

PMID- 22413987
TI  - Looking ahead: clinical trial design in adult congenital heart disease.
AB  - Continued growth in the field of adult congenital heart disease has given rise to
      a critical mass of patients, investigators and resources dedicated to advancing
      knowledge through research. Impressive gains over the past decade have largely
      been driven by successful observational studies. Despite the privileged role of
      clinical trials in the hierarchy of evidence-based medicine, few such studies
      have thus far been conducted in adult congenital heart disease. Obstacles and
      challenges particular to clinical trials in adult congenital heart disease are
      addressed in this review. In looking ahead, examples of creative methodological
      solutions to maximizing the efficiency of clinical trials for rare diseases are
      discussed, including Bayesian analyses, outcome-adaptive randomization and
      internal pilot studies.

PMID- 22413986
TI  - Robotics and imaging in congenital heart surgery.
AB  - The initial success seen in adult cardiac surgery with the application of
      available robotic systems has not been realized as broadly in pediatric cardiac
      surgery. The main obstacles include extended set-up time and complexity of the
      procedures, as well as the large size of the instruments with respect to the size
      of the child. Moreover, while the main advantage of robotic systems is the
      ability to minimize incision size, for intracardiac repairs, cardiopulmonary
      bypass is still required. Catheter-based interventions, on the other hand, have
      expanded rapidly in both application as well as the complexity of procedures and
      lesions being treated. However, despite the development of sophisticated devices,
      robotic systems to aid catheter procedures have not been commonly applied in
      children. In this article, we describe new catheter-like robotic delivery
      platforms, which facilitate safe navigation and enable complex repairs, such as
      tissue approximation and fixation, and tissue removal, inside the beating heart.
      Additional features including the tracking of rapidly moving tissue targets and
      novel imaging approaches are described, along with a discussion of future
      prospects for steerable robotic systems.

PMID- 22413988
TI  - Changing lesion demographics of the adult with congenital heart disease: an
      emerging population with complex needs.
AB  - The demography of congenital heart disease is changing. Largely as a consequence
      of successful cardiac surgery in childhood, there are an increasing number of
      adults with congenital heart disease with a prevalence of more than four per 100
      adults. The type of disease in adults is also changing with an increasing number
      of survivors with complex disease. These patients have a significantly increased
      healthcare requirement in comparison to healthy adults and this includes
      noncardiac, multisystem morbidity. The adult congenital heart disease population
      are now developing problems associated with aging and there is a new population
      of geriatrics with congenital heart disease. As survival continues to improve,
      increased healthcare resources need to be directed towards the management of the
      adult with congenital heart disease.

PMID- 22413989
TI  - Cardiac risks and management of complications in pregnant women with congenital
      heart disease.
AB  - There are a growing number of women with congenital heart disease reaching
      adulthood and contemplating and/or undergoing pregnancy. However, pregnancy
      imposes hemodynamic stress on the heart and this can result in maternal, fetal
      and neonatal complications. Most women with congenital heart disease do well
      during pregnancy, but some women with high-risk cardiac lesions will not tolerate
      the hemodynamic changes of pregnancy. Physicians must be aware of the potential
      risks for the mother both during and after pregnancy, the risks to the fetus and
      neonate, and the risks and benefits of medications and procedures used during
      pregnancy. For women with complex cardiac conditions, management during pregnancy
      benefits from multidisciplinary care involving cardiologists with expertise in
      pregnancy, obstetricians with expertise in maternal fetal medicine,
      neonatologists and obstetric anesthetists, among others. This review will focus
      on the cardiac risks faced by women with congenital heart disease; particularly
      those at high risk, and on management strategies to mitigate risk and address
      cardiac complications.

PMID- 22413990
TI  - Heart transplantation in adults with end-stage congenital heart disease.
AB  - Residual abnormalities in cardiac structure and function predispose adults with
      congenital heart disease to late-onset heart failure and its complications.
      Evaluation of this population requires collaboration between adult congenital and
      heart failure specialists. In addition to assessing heart transplant eligibility,
      clinicians must balance the risks of premature listing against progressive heart
      failure and increased waiting list mortality. Following heart transplantation,
      adults with congenital heart disease have higher mortality due to an increased
      risk of bleeding, infection and donor right heart failure secondary to pulmonary
      hypertension. Concerns relating to increased early mortality should be balanced
      against superior long-term survival in adult congenital heart disease patients
      surviving beyond the first year after heart transplantation.

PMID- 22413991
TI  - Molecular mechanisms of the PRL phosphatases.
AB  - The phosphatases of regenerating liver (PRLs) are an intriguing family of dual
      specificity phosphatases due to their oncogenicity. The three members are small,
      single domain enzymes. We provide an overview of the phosphatases of regenerating
      liver, compare them to related phosphatases, and review recent reports about each
      phosphatase. Finally, we discuss similarities and differences between the
      phosphatases of regenerating liver, focusing on their molecular mechanisms and
      signalling pathways.

PMID- 22413992
TI  - Value of three-dimensional contrast-enhanced power Doppler ultrasound for
      characterizing adnexal masses.
AB  - AIMS: The aim of this study was to assess the diagnostic performance of 3-D
      contrast-enhanced power Doppler ultrasonography (3-D CEPDUS) for differentiating
      benign and malignant adnexal masses. MATERIAL AND METHODS: Consecutive patients
      with adnexal masses were included prospectively and underwent 2-D ultrasonography
      and 3-D CEPDUS in a tertiary centre in Paris, France. The main outcome measure
      was the diagnostic accuracy of 3-D CEPDUS to diagnose malignant and borderline
      adnexal masses. The reference standard was the final histological examination.
      Two-dimensional ultrasonography and 3-D CEPDUS were compared using
      semiquantitative scores. Three-dimensional CEPDUS assessed vessel density, vessel
      pattern, and three vascular indexes in a 5-mL region of interest (vascularization
      index [VI], flow index [FI], and vascularization flow index [VFI]). The 2-D and 3
      D examinations were done by different sonographers who were blinded to the other
      test. The pathologist was blinded to ultrasonography findings. RESULTS: Of 99
      patients, 88 had benign tumors and were compared to the 11 patients with
      borderline (n = 5) or malignant (n = 6) tumors. The sensitivity of the subjective
      2-D score was 55% (95% confidence interval [CI], 25-84) and specificity 94%
      (95%CI, 89-99). The sensitivity of the subjective 3-D score was 82% (95%CI, 58
      100) and specificity 90% (95%CI, 83-96). Improvement of detection of malignant or
      borderline tumors by subjective 3-D score was 150%. Vessel density and patterns
      were not more efficient than the subjective 3-D score. The mean vascular index
      values were significantly different between benign and borderline/malignant
      groups: VI, 7.2 versus 35.5 (P < 0.0001); FI, 37.0 versus 48.2 (P = 0.003); and
      VFI, 2.9 versus 17.6 (P < 0.0001), respectively. CONCLUSIONS: 3-D CEPDUS improves
      detection of malignant and borderline adnexal masses.

PMID- 22413993
TI  - Unusual presentation of metastatic Ewing sarcoma to the ovary in a 13 year-old: a
      case report and review.
AB  - Ewing sarcoma (ES) is the second most common bone malignancy in children and
      adolescents. Together with primitive neuroectodermal tumors (PNET), ES comprises
      the PNET/ES family. Metastasis is present in about 25% of patients at diagnosis
      and is most commonly found in the lung and bones. Primary PNET/ES of the ovary
      has been reported in many adult cases; however, secondary occurrences are rare.
      Here we present the clinical course of a 13-year-old patient with metastatic ES
      to the ovary without involvement of any other sites. To our knowledge, this is
      the second reported pediatric case of metastatic ES to the ovary.

PMID- 22413994
TI  - Centromeric association of small supernumerary marker chromosomes with their
      sister-chromosomes detected by three dimensional molecular cytogenetics.
AB  - BACKGROUND: Small supernumerary marker chromosomes (sSMC) are detected in 0.043%
      of general population and can be characterized for their chromosomal origin,
      genetic content and shape by molecular cytogenetic approaches. Even though
      recently progress was achieved towards genotype-phenotype-correlations of sSMC,
      nothing is known on the influence that an additional derivative extra chromosome
      has on the nuclear architecture. RESULTS: Here we present the first three
      dimensional interphase fluorescence in situ hybridization (FISH) studies for the
      nuclear architecture of sSMC. It could be shown that sSMC derived from
      chromosomes 15, 16 or 18 preferentially colocalized with one of their
      corresponding sister chromosomes. This was true in B- and T-lymphocytes as well
      as in skin fibroblasts. Additionally, a case with a complex sSMC with a karyotype
      47,XY,+der(18)t(8;18)(8p23.2 ~ 23.1;18q11.1) was studied. Here the sSMC co
      localized with one homologous chromosome 8 instead of 18. CONCLUSION: Overall,
      there is a kind of "attraction" between an sSMC and one of its homologous sister
      chromosomes. This seems to be transmitted by the euchromatic part of the sSMC
      rather than its heterochromatic one.

PMID- 22413995
TI  - Commentary on Caetano, Mills, and Vaeth (2012): the role of context on alcohol
      consumption among Mexican Americans.
AB  - BACKGROUND: In this commentary, we discuss a study by Caetano and colleagues
      (2012) that examines alcohol consumption and binge drinking behavior among U.S.
      Mexico border and non-border Mexican Americans using data from the Hispanic
      Americans Baseline Alcohol Survey. METHODS: We discuss how Caetano and colleagues
      (2012) addressed 3 gaps in our understanding of drinking behaviors among
      Hispanics: (1) effects of living near the U.S.-Mexico border, (2) gender
      differences in drinking behaviors, and (3) alcohol-related outcomes among young
      women. RESULTS: Findings suggest that Mexican American men and women living along
      the U.S.-Mexico border reported higher levels of drinking than their U.S.
      metropolitan counterparts (Caetano et al., 2012). CONCLUSIONS: This study
      represents an important contribution to the dearth of studies investigating
      disparities in alcohol-related consequences among Hispanic young adults living
      along the U.S.-Mexico border. Future research needs to examine why contextual
      factors of the U.S.-Mexico border generate differential effects in the Mexican
      American population.

PMID- 22413996
TI  - Vitamin supplementation and blood pressure in Type 2 diabetes.
AB  - AIMS: Vitamin D levels are inversely related to blood pressure. Given that low
      sun exposure can create a greater reliance on dietary sources of vitamin D, we
      aimed to determine whether dietary vitamin D and blood pressure associations
      differ between periods of low and high sun exposure. METHODS: Dietary intake,
      vitamin supplementation, blood pressure, and anthropometric parameters were
      assessed each season for 1 year (174 adults with Type 2 diabetes). Separate
      linear regression models were constructed for high and low sun exposure periods
      to examine associations of systolic blood pressure with dietary vitamin D intake
      and vitamin supplement use (adjusted for age, gender, BMI, ethnicity, smoking,
      alcohol, physical activity, antihypertensive medication and nutrient intake).
      Robustness of findings was confirmed with within-subject repeated measures
      analysis, including an interaction term for sun exposure period. RESULTS: Vitamin
      D intake from food sources was low year-round and no conclusive association with
      blood pressure was identified during either period. Systolic blood pressure was
      5.1 mmHg lower during the low sun exposure period (95% CI 0.5-9.7) in daily
      supplement users compared with non-users. The interaction term between supplement
      use and sun exposure period was significant (low sun exposure* no supplement, P =
      0.02). Systolic blood pressure was relatively stable in users (low and high sun
      exposure periods, respectively, mean +/- SE: 135.2 +/- 2.6 mmHg and 134.2 +/- 2.5
      mmHg), but not in non-users (140.2 +/- 2.7 mmHg and 130.5 +/- 2.5 mmHg).
      CONCLUSIONS: Vitamin supplementation may stabilize systolic blood pressure in
      adults with Type 2 diabetes across seasons.

PMID- 22413997
TI  - Concepts for designing and fabricating metal implant frameworks for hybrid
      implant prostheses.
AB  - Edentulous patients have reported difficulties in managing complete dentures;
      they have also reported functional concerns and higher expectations regarding
      complete dentures than the dentists who have treated them. Some of the objectives
      of definitive fixed implant prosthodontic care include predictable, long-term
      prostheses, improved function, and maintenance of alveolar bone. One of the keys
      to long-term clinical success is the design and fabrication of metal frameworks
      that support implant prostheses. Multiple, diverse methods have been reported
      regarding framework design in implant prosthodontics. Original designs were
      developed empirically, without the benefit of laboratory testing. Prosthetic
      complications reported after occlusal loading included screw loosening, screw
      fracture, prosthesis fracture, crestal bone loss around implants, and implant
      loss. Numerous authors promoted accurately fitting frameworks; however, it has
      been noted that metal frameworks do not fit accurately. Passively fitting metal
      implant frameworks and implants have not been realized. Biologic consequences of
      ill-fitting frameworks were not well understood. Basic engineering principles
      were then incorporated into implant framework designs; however, laboratory
      testing was lacking. It has been reported that I- and L-beam designs were the
      best clinical option. With the advent of CAD/CAM protocols, milled titanium
      frameworks became quite popular in implant prosthodontics. The purpose of this
      article is to discuss current and past literature regarding implant-retained
      frameworks for full-arch, hybrid restorations. Benefits, limitations, and
      complications associated with this type of prosthesis will be reviewed. This
      discussion will include the relative inaccuracy of casting/implant fit and
      improved accuracy noted with CAD/CAM framework/implant fit; cantilever extensions
      relative to the A/P implant spread; and mechanical properties associated with
      implant frameworks including I- and L-beam designs. Guidelines will be proposed
      for use by clinicians and laboratory technicians in designing implant-retained
      frameworks.

PMID- 22413998
TI  - Bioactivity-guided fractionation of the triglyceride-lowering component and in
      vivo and in vitro evaluation of hypolipidemic effects of Calyx seu Fructus
      Physalis.
AB  - BACKGROUND: In folklore, some people take the decoction of Calyx seu Fructus
      Physalis (CSFP) for lowering blood lipids. The present study is designed to
      evaluate the lipid-lowering activities of CSFP, and search for its
      pharmacodynamical material. METHODS: CSFP was extracted by water and 75% ethanol,
      respectively. The extracts of CSFP for reducing serum lipid levels were evaluated
      on mouse model of hyperlipidemia. The optimized extract was subjected to the
      bioactivity-guided fractionation in which the liquid-liquid extraction, collumn
      chromatography, the in vivo and in vitro models of hyperlipidemia were utilized.
      The structure of active component was determined by 13C-NMR and 1H-NMR. RESULTS:
      The 75% ethanol extract of CSFP decreased the serum total cholesterol (TC) and
      triglyceride (TG) levels in mouse model of hyperlipidemia. Followed a separation
      process for the 75% ethanol extract of CSFP, the fraction B was proved to be an
      active fraction for lowering lipid in vivo and in vitro experiments, which could
      significantly decrease the serum TC and TG levels in mouse model of
      hyperlipidemia, and remarkably decrease the increase of TG in primary mouse
      hepatocytes induced by high glucose and the increase of TG in HepG2 cells induced
      by oleic acid. The fraction B2, isolated from B on bioactivity-guided
      fractionation, could significantly decrease TG level in HepG2 cells. One compound
      with the highest content in B2 was isolated and determined as luteolin-7-O-beta-D
      glucopyranoside by NMR spectra. It could significantly reduce the TG level in
      HepG2 cells, and inhibited the accumulation of lipids by oil red O stain.
      CONCLUSION: Our results demonstrated that the 75% ethanol extract of CSFP could
      improve in vitro and in vivo lipid accumulation. Luteolin-7-O-beta-D
      glucopyranoside might be a leading pharmacodynamical material of CSFP for
      lowering lipids.

PMID- 22413999
TI  - Traumatic brain injury increased IGF-1B mRNA and altered IGF-1 exon 5 and
      promoter region epigenetic characteristics in the rat pup hippocampus.
AB  - Traumatic brain injury (TBI) is a major cause of acquired cognitive disability in
      childhood. Such disability may be blunted by enhancing the brain's endogenous
      neuroprotective response. An important endogenous neuroprotective response is the
      insulin-like growth factor-1 (IGF-1) mRNA variant, IGF-1B. IGF-1B mRNA,
      characterized by exon 5 inclusion, encodes the IGF-1 and Eb peptides. IGF-1A mRNA
      excludes exon 5 and encodes the IGF-1 and Ea peptides. A region in the human IGF
      1B homologue acts as an exon-splicing enhancer (ESE) to increase IGF-1B mRNA. It
      is not known if TBI is associated with increased brain IGF-1B mRNA. Epigenetic
      modifications may underlie altered gene expression in the brain after TBI. We
      hypothesized that TBI would increase hippocampal IGF-1B mRNA in 17-day-old rats,
      associated with DNA methylation and/or histone modifications at the promoter site
      1 (P1) or exon 5/ESE region. Hippocampi from rat pups after controlled cortical
      impact (CCI) were used to measure IGF-1B mRNA, DNA methylation, and histone
      modifications at the P1, P2, and exon5/ESE regions. In CCI hippocampi, IGF-1B
      mRNA peaked at post-injury day (PID) 2 (1700+/-320% sham), but normalized by PID
      14. IGF-1A peaked at PID 3 (280+/-52% sham), and remained elevated at PID 14.
      Increased IGF-1B mRNA was associated with increased methylation at P1, and
      increased histone modifications associated with gene activation at P2 and
      exon5/ESE, together with differential methylation in the exon 5/ESE regions. We
      report for the first time that hippocampal IGF-1B mRNA increased after
      developmental TBI. We speculate that epigenetic modifications at the P2 and exon
      5/ESE regions are important in the regulation of IGF-1B mRNA expression. The exon
      5/ESE region may present a means for future therapies to target IGF-1B
      transcription after TBI.

PMID- 22414000
TI  - Blood Epstein-Barr virus DNA load and risk of progression to AIDS-related
      systemic B lymphoma.
AB  - BACKGROUND: AIDS-related lymphoma (ARL) remains the main cause of AIDS-related
      deaths in the combined antiretroviral therapy (cART) era. Although most ARLs are
      associated with the Epstein-Barr virus (EBV), whether patients with high EBV
      burden are more at risk of developing ARL is unknown. This study investigated the
      relationship between high blood EBV DNA loads and subsequent progression to ARL.
      METHODS: We identified 43 cases of ARL diagnosed between 1988 and 2007 within two
      cohorts (ANRS SEROCO/HEMOCO and PRIMO) and for which stored serum and peripheral
      blood mononuclear cell (PBMC) samples were available within 3 years before ARL
      diagnosis. For each case, two controls matched for the cohort and CD4 cell count
      in the year of ARL diagnosis were selected. EBV DNA was measured in PBMCs and
      serum samples with a commercial kit. RESULTS: High levels of EBV DNA in PBMCs
      collected a median of 10 months before diagnosis were associated with an
      increased risk of developing systemic B lymphoma (adjusted odds ratio 2.47; 95%
      confidence interval 1.15; 5.32 for each 1 log copies/10(6) PBMC increase in EBV
      load) but not with primary brain lymphoma. CONCLUSION: In this study, HIV
      infected patients with undetectable EBV DNA in PBMCs did not develop ARL in the
      following 3 years, while high levels of EBV DNA in PBMCs predicted subsequent
      progression to systemic B lymphoma. Clinicians should be aware of the increased
      risk of developing systemic B lymphoma in HIV-infected patients with a high blood
      EBV DNA load.

PMID- 22414001
TI  - Silencing thioredoxin induces liver cancer cell senescence under hypoxia.
AB  - AIM:   Although thioredoxin 1 (TXN) has pleiotropic cellular functions as a redox
      sensitive protein, very little is known about its role in tumor survival and
      growth under hypoxia. MHCC97H hepatocellular carcinoma cells have a high
      metastatic potential and high thioredoxin expression levels compared with their
      parent cell line, MHCC97. Thus, we used this cell line to explore the functional
      connections between TXN and hypoxia. METHODS:   MHCC97H cells were cultured under
      normoxia and hypoxia for specific periods after nucleofection with TXN siRNA or
      control siRNA. We assessed the beta-phenylethyl isothiocyanate (PEITC)
      sensitivity of the cells, cell proliferation, cell cycle and senescence, and DNA
      damage response by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assays, colony formation assays, flow cytometry, beta-galactosidase
      staining, western blotting, and immunohistochemistry. RESULTS:   beta-phenylethyl
      isothiocyanate treatment shifted reduced TXN to oxidized TXN in MHCC97H cells.
      Although silencing of TXN via siRNA had no effect on the PEITC sensitivity of the
      cells, it suppressed cell proliferation and colony formation under both normoxia
      and hypoxia. Under hypoxia, silencing TXN did not induce apoptosis but induced
      DNA damage response and cellular senescence. CONCLUSIONS:   High TXN levels in
      MHCC97H cells protect them from DNA damage and cellular senescence under hypoxia.
      Targeting TXN might enhance the chemotherapeutic effects of some DNA-damaging
      agents against hepatocellular carcinoma.

PMID- 22414002
TI  - Classification of cultivation locations of Panax quinquefolius L samples using
      high performance liquid chromatography-electrospray ionization mass spectrometry
      and chemometric analysis.
AB  - Panax quinquefolius  L ( P. quinquefolius  L) samples grown in the United States
      and China were analyzed with high performance liquid chromatography-mass
      spectrometry (HPLC-MS). Prior to classification, the two-way data sets were
      subjected to pretreatment including baseline correction and retention time (RT)
      alignment. Principal component analysis (PCA) and projected difference resolution
      (PDR) metrics were used to evaluate the data quality and the pretreatment
      effects. A fuzzy rule-building expert system (FuRES) classifier was used to
      classify the  P. quinquefolius  L samples grown in the United States and China
      with the optimized partial least-squares (o-PLS) classifier as the positively
      biased control method. A classification rate as high as 98 +/- 3% with FuRES was
      obtained after baseline correction and RT alignment, which is equivalent to the
      result obtained by using the positively biased o-PLS control method (98 +/- 3%).
      RT alignment improved the classification rates for both FuRES and o-PLS
      classifiers (18% improvement for the FuRES classification rate and 10%
      improvement for the o-PLS classification rate with baseline correction). From the
      rule obtained to classify the  P. quinquefolius  L samples grown in the United
      States and China, peaks were identified that can be prospective biomarkers for
      differentiating samples from different growth regions. HPLC-MS with chemometric
      analysis has the potential to be used as an authentication method for  P.
      quinquefolius  L grown in China and the United States.

PMID- 22414003
TI  - How we treat: risk mitigation for ABO-incompatible plasma in plateletpheresis
      products.

PMID- 22414004
TI  - Prevalence, pattern, sensitivity and resistance to antibiotics of different
      bacteria isolated from port site infection in low risk patients after elective
      laparoscopic cholecystectomy for symptomatic cholelithiasis at tertiary care
      hospital of Kashmir.
AB  - The aim of this study was to determine specific pattern of port site microbial
      colonisation, sensitivity and resistance to different antibiotics of bacteria
      isolated from port site infection (PSI) in low risk patients after elective
      laparoscopic cholecystectomy in surgical wards at tertiary care hospital of
      Kashmir. This is a prospective study. The study included 675 consecutive patients
      of postoperative PSI after elective laparoscopic cholecystectomy for symptomatic
      cholelithiasis over a period of 12 months. Culture swabs were taken from port
      sites with signs of PSI and transported to the microbiology laboratory. The
      positive swab cultures were subjected to antibiotic susceptibility test. The data
      obtained was analysed by using appropriate statistical analytical tests. The
      incidence of PSI after elective laparoscopic cholecystectomy is 6.7%. The
      commonest organism responsible for PSI is pseudomonas, 19 (42.2%) cases. Most of
      the strains of organisms isolated were resistant to commonly used antibiotics in
      the hospital,pseudomonas was found 100% resistant to the combination of
      ampicillin + sulbactum and ceftriaxone and it was sensitive to imipenem, amikacin
      and vancomycin in 89.47,57 and 52.63% of cases respectively. Our study will be
      helpful in choosing effective empirical prophylactic antibiotic therapy in cases
      of elective laparoscopic cholecystectomy and will have a great impact on
      morbidity and mortality in them because of PSI.

PMID- 22414005
TI  - Discrepancy between human T-cell lymphotropic virus type I screening test and
      confirmatory tests in non-endemic areas.
AB  - AIM: The purpose of this study was to examine the seroprevalence of human T
      lymphotropic virus (HTLV)-I among pregnant women at our institution in Tokyo,
      Japan, which is a non-endemic area, and to investigate the results of Western
      blotting among pregnant women who had obtained positive results from a screening
      test. MATERIAL AND METHODS: The seroprevalence of HTLV-I was retrospectively
      reviewed in 11,352 pregnant women who gave birth at the National Center for Child
      Health and Development in Tokyo, Japan, between 2002 and 2009. For the screening
      test, a chemiluminescent enzyme immunoassay was performed followed by a
      confirmatory Western blot test. RESULTS: The overall positive rate for the
      screening test was 0.33% (37/11,352). Western blot testing was performed in 36 of
      these 37 cases. Only nine patients (25%) were positive for HTLV-I by Western blot
      testing, seven patients (19%) were indeterminate, and 20 patients (56%) were
      negative. CONCLUSIONS: In this study (carried out in a non-endemic area), the
      percentage of patients with a positive result from the screening test who were
      confirmed to be true carriers was significantly low, differing from endemic
      areas.

PMID- 22414006
TI  - Myofibroblastoma of breast in a male infant.
AB  - Breast masses are very rare in infants and premature telarche due to excessive
      endogen or exogenous estrogens is the most common presentation during infancy.
      Myofibroblastoma is a stromal tumor of the breast, occurring especially in elder
      males. This breast mass has a close relationship between androgen receptors and
      has not been reported in infants previously. A 10-month old male baby with a left
      breast mass, which is diagnosed as myofibroblastoma, is discussed to evaluate the
      clinical features and treatment modalities of breast myofibroblastomas in
      children.

PMID- 22414007
TI  - Commentary with regard to the role of alcohol and cofactors in the development of
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a primary cancer of the liver. It is clear that
      chronic alcohol abuse is associated with the development of HCC, but the
      mechanistic role of alcohol in HCC is not well studied. The research that is
      presented in the Brandon-Warner and colleagues' (2012) article approaches an
      important outcome of chronic alcohol abuse. The most important study results that
      are presented in their article show convincing data that chronic alcohol
      consumption by male mice resulted in a robust response in the liver to a
      carcinogen. It was shown that female mice responded significantly less to alcohol
      and the carcinogen than the male animals. The overall research data covered a
      number of aspects of the liver disease associated with chronic alcohol
      consumption and the presence of a carcinogen that will support a great deal of
      further research to develop mechanistic data.

PMID- 22414008
TI  - Two novel GPER agonists induce gene expression changes and growth effects in
      cancer cells.
AB  - Although the action of estrogens has been traditionally explained by the binding
      to and transactivation of the nuclear estrogen receptor (ER)alpha and ERbeta,
      recently the G protein-coupled receptor GPR30/GPER has been involved in the rapid
      estrogen signaling. We investigated the ability of two original molecules, which
      were named GPER-L1 and GPERL2, to bind to and activate the GPER transduction
      pathway in cancer cells. Competition assays, docking simulations, transfection
      experiments, real-time PCR, immunoblotting, gene silencing technology and growth
      assays were performed to ascertain the selective action of GPER-L1 and GPER-L2 in
      activating the GPER-mediated signaling. Both compounds, which did not show any
      ability to bind to and activate the classical ERs, were able to bind to GPER and
      to trigger the rapid activation of the GPER/EGFR/ERK transduction pathway which
      led to the up-regulation of GPER-target genes. Notably, GPER-L1 and GPER-L2
      induced the proliferation of SkBr3 breast and Ishikawa endometrial cancer cells
      at nM concentrations through GPER, hence providing further evidence on their
      capability to elicit relevant biological responses mediated by GPER. The
      identification and characterization of these novel compounds as selective GPER
      agonists represent a valuable tool to further dissect the pharmacology of this
      novel estrogen receptor and to better differentiate the specific functions
      elicited by each estrogen receptor subtype in cancer cells.

PMID- 22414009
TI  - Recent findings confirm LIM domain kinases as emerging target candidates for
      cancer therapy.
AB  - The two members of the LIM domain kinase family (LIMK1 and LIMK2) represent
      crucial keys in the signaling pathways that modulate the structure and activity
      of actin cytoskeleton. They maintain the optimal balance between phosphorylated
      and unphosphorylated cofilin that in turn acts by severing filamentous actin into
      globular actin and ensures actin turnover and cytoskeleton regulation. Many
      macromolecular partners able to regulate LIMK activity (positive and negative
      regulators) do exist. Proteins that enhance or reduce the nucleocytoplasmic
      shuttling of LIMK by direct or indirect interaction are also known. Among many
      LIMK activators, members of the Rho family of small GTPases (i.e., Rho, Rac, and
      Cdc42) and their downstream effectors (i.e., ROCK, PAK, and MK2) are involved in
      the progression of various human cancers toward invasive and metastatic stages.
      As LIMK are centrally positioned in the pathways leading to cytoskeleton dynamics
      and regulation, they could be considered as valuable targets for actin
      regulation. Fine modulation of LIMK activity could be a major challenge to
      inhibit tumor cell invasion mediated by one or a combination of the upstream
      signaling factors. As LIMK play a critical role in tumor cell invasion, they may
      be candidate targets for developing novel therapeutic agents toward tumor
      invasion and metastasis.

PMID- 22414010
TI  - New strategies in the chemotherapy of leukemia: eradicating cancer stem cells in
      chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the
      Philadelphia-positive chromosome deriving from a translocation between
      chromosomes 22 and 9. The oncogenic product of this aberrant chromosome is the
      constitutively active tyrosine kinase BCR-ABL that is responsible for leukemic
      cell growth, proliferation and survival driven by the dysregulation of a large
      array of signal transduction pathways. Inhibition of BCR-ABL with tyrosine kinase
      inhibitors proved to be an efficient therapy of CML in the chronic phase.
      Unfortunately, the impressive success of BCR-ABL inhibitors as front-line therapy
      in CML has been tempered by problems of disease persistence or relapse arising
      from different mechanisms, including mutations in the kinase domain of the enzyme
      BCRABL and mechanisms independent from BCR-ABL activity. Growing evidence has
      also suggested a pivotal role of persistent leukemic cancer stem cells,
      characterized by high self-renewal and pluripotency, in CML maintenance and/or
      relapse. The present review deals with the most recent advances in this
      challenging field and focuses on the development of new drugs and therapeutic
      approaches to eradicate the subtle and dangerous leukemic stem cells responsible
      for maintaining and sustaining tumor growth.

PMID- 22414011
TI  - Multifaceted mechanisms for cell survival and drug targeting in chronic
      myelogenous leukemia.
AB  - Treatment outcomes for chronic myelogenous leukemia (CML) have shown major
      improvements as a result of the development of the tyrosine kinase inhibitors
      (TKIs) imatinib, nilotinib and dasatinib for the disease-specific molecular
      target BCR-ABL1 tyrosine kinase (TK), but a cure of CML by BCR-ABL1 TKIs has been
      rarely achieved. CML cells are protected from cytotoxic insults, including those
      by TKIs, through various collaborative BCR-ABL1- mediated and -independent
      mechanisms, as well as cell-intrinsic and -extrinsic molecular mechanisms. These
      protective mechanisms include overlapping cell signaling pathways for normal
      hematopoietic proliferation, modulation of molecules associated with the BCL2
      family protein-regulated programmed cell death pathway, autophagic cell
      protection capability, bone marrow environment-mediated cell protective
      signaling, abnormally upregulated genetic instability and other BCR-ABL1-
      independent kinase activities. To develop a more effective treatment strategy for
      a cure by means of total leukemic cell killing, a thorough understanding of how
      CML cells survive and resist cytotoxic insults is essential. In this article, we
      review current knowledge about multifaceted BCR-ABL1-related and -unrelated
      mechanisms for survival and death of CML cells and present suggestions for the
      development of new therapeutic strategies for complete elimination of residual
      CML cells during TKI treatment.

PMID- 22414012
TI  - Antitumor effects of interferon-alpha on cell growth and metastasis in human
      nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a highly malignant and frequently metastasized
      tumor, and the prognosis is very poor when distant metastases occur. Recently,
      immunotherapy is becoming a promising therapeutic approach. Interferon-alpha (IFN
      alpha) represents the cytokines exhibiting the longest record of use in clinical
      oncology. In this study, we examined the antitumor effects of IFN-alpha1b on NPC.
      The results showed that recombinant human IFN-alpha1b (hIFN-alpha1b) suppressed
      cell growth, induced a G1-phase cell cycle arrest in vitro, increased the
      expression of p16 and pRb, and decreased the expression of CCND1 and CDK6. In
      vivo analyses showed that either recombinant adeno-associated virus (rAAV)-IFN
      alpha1b or hIFN-alpha1b treatment inhibited tumor growth and metastasis, reduced
      intratumoral microvessel density, increased cell apoptosis and necrosis, and
      induced prolonged survival. Notably, rAAV-IFN-alpha1b or hIFN-alpha1b treatment
      led to significantly higher serum levels of IL-12 and GM-CSF in mice compared to
      respective controls. Our findings suggest that IFN-alpha1b acts as a
      multifunctional antitumor agent in NPC, which may have important therapeutic
      implications.

PMID- 22414013
TI  - Bisquinolinium compounds induce quadruplex-specific transcriptome changes in HeLa
      S3 cell lines.
AB  - BACKGROUND: Guanosine rich sequences capable of forming G-quadruplex (G4) motifs
      are enriched near the gene transcription start site (TSS) in the human genome.
      When probed at the single gene level, G-quadruplex motifs residing in promoter
      regions show substantial effects on gene transcription. Moreover, further changes
      in transcription levels are noticed when G4-motifs are targeted with G-quadruplex
      specific small molecules. RESULTS: Global studies concerning general changes of
      the transcriptome via targeting promoter-based G-quadruplex motifs are very
      limited and have so far only been carried out with compounds displaying weak
      selectivity for quadruplex sequences. Here we utilize two G-quadruplex-specific
      bisquinolinium derivatives PhenDC3 and 360A and investigate their effects on the
      expression of the HeLa S3 transcriptome. Our results show wide-spread changes in
      the transcriptome with specificity for genes with G-quadruplex motifs near their
      transcription start sites (TSS). Using real-time PCR we further confirmed the
      specificity of PhenDC3 and 360A as potent molecules to target G-quadruplex
      regulated genes. CONCLUSIONS: Specific effects on quadruplex-containing genes
      have been observed utilizing whole-transcriptome analysis upon treatment of
      cultured cells with quadruplex-selective bisquinolinium compounds.

PMID- 22414014
TI  - Balancing cost and precision in hospital accountability sampling.
AB  - The purpose of this article is to examine the relationship between sample size
      and cost using a benefit to cost ratio in the context of hospital accountability
      measures. We argue that the decision to use larger samples should include an
      assessment of the marginal benefit in terms of the cost to obtain the samples.
      Our main conclusion is that without recognizing and balancing the cost of
      different sampling schemes and developing reasonable cost limits we lose an
      opportunity at efficiency.

PMID- 22414015
TI  - Measuring multidisciplinary team effectiveness in a ward-based healthcare
      setting: development of the team functioning assessment tool.
AB  - Nontechnical skills relating to team functioning are vital to the effective
      delivery of patient care and safety. In this study, we develop a reliable
      behavioral marker tool for assessing nontechnical skills that are critical to the
      success of ward-based multidisciplinary healthcare teams. The Team Functioning
      Assessment Tool (TFAT) was developed and refined using a literature review, focus
      groups, card-sorting exercise, field observations, and final questionnaire
      evaluation and refinement process. Results demonstrated that Clinical Planning,
      Executive Tasks, and Team Relations are important facets of effective
      multidisciplinary healthcare team functioning. The TFAT was also shown to yield
      acceptable inter-rater agreement.

PMID- 22414016
TI  - Interview with a quality leader: Dr. Suzanne Delbanco, on healthcare payment
      reform. Interviewed by Kevin Warren.
AB  - Suzanne F. Delbanco is the executive director of Catalyst for Payment Reform
      (CPR), a nonprofit organization working for coordinated action among the largest
      purchasers of healthcare and health plans to reform the way we pay for healthcare
      in the United States to improve quality and cost. In addition to her duties at
      CPR, Suzanne is on the Advisory Committee to the Director and the National
      Biosurveillance Advisory Subcommittee of the Centers for Disease Control and
      Prevention. She also serves on the boards of HCI3, the Anvita Health Advisory
      Council, the executive committee of the California Maternal Quality Care
      Collaborative, and participates in the Healthcare Executives Leadership Network.
      Before CPR, Suzanne was President, Health Care Division at Arrowsight Inc., a
      company using video to help hospitals measure the performance of healthcare
      workers and provide them with feedback while they are working to improve
      adherence to safety and quality protocols. From 2000 to 2007, Suzanne was the
      founding CEO of The Leapfrog Group. The Leapfrog Group uses the collective
      leverage of its large corporate and public members to initiate breakthrough
      improvements in the safety, quality, and affordability of healthcare for
      Americans. Before joining Leapfrog, Suzanne was a senior manager at the Pacific
      Business Group on Health where she worked on the Quality Team. Suzanne holds a
      PhD in Public Policy from the Goldman School of Public Policy and a MPH from the
      School of Public Health at the University of California, Berkeley.

PMID- 22414017
TI  - Measuring body mass index according to protocol: how are height and weight
      obtained?
AB  - Previous investigation at our resident-teaching, family medicine clinics
      determined that >80% of adult patients have body mass index (BMI) recorded in the
      electronic medical record. The quality of this measure, however, is not known.
      The objective of this study was to determine the accuracy of documented BMI. We
      used an observational study design to determine the means by which clinic staff
      obtain height and weight values from patients. We found that staff only obtained
      35.4% of these measurements according to protocol. The major reason for
      noncompliance with protocol was that shoes were not removed for the measurements.
      Our investigation indicated that providers, quality improvement teams, and
      researchers should not assume the accuracy of the recorded BMI. Future
      investigation is warranted to improve the quality of these measurements in the
      outpatient setting.

PMID- 22414018
TI  - Study on defensive medicine practices among obstetricians and gynecologists who
      provide breast care.
AB  - The purpose of this study was to assess malpractice concerns, career
      satisfaction, defensive medicine, experience with liability lawsuits, and changes
      in breast care practices among obstetricians and gynecologists (ob-gyns) who
      provide breast care. Four hundred ACOG Fellows were randomly selected and invited
      to participate, 247 (62%) responded. A majority of responders had increased the
      number of referrals for the diagnosis of breast abnormalities (58.9%) and
      treatment of breast disease (53.6%) due to fears and concerns regarding
      malpractice. On average, there was a high level of career satisfaction (M=8.5
      [SD=2.5] on a scale from 0 to 10); however, those who had been sued were
      significantly less satisfied than those who had not. Physicians who had decreased
      breast surgical procedures and increased referrals for diagnosis and treatment of
      breast disease reported practicing defensive medicine more frequently. In a
      regression analysis, having been sued was a significant predictor of practicing
      defensive medicine more often. Physicians from states with malpractice crisis
      reported practicing defensive medicine more frequently and more lawsuits than
      physicians from stable states. Malpractice fears and defensive medicine continue
      to affect the practices of ob-gyns, most specifically, as this study shows, ob
      gyns who provide breast care.

PMID- 22414019
TI  - Association of patient recognition of inpatient physicians with knowledge and
      satisfaction.
AB  - Patient recognition of hospital providers is low and may affect patient knowledge
      and satisfaction with care. Our study aimed to determine the association between
      patient knowledge of their inpatient providers' face, name, or role with
      knowledge of their diagnosis, satisfaction with care, and 30-day readmission
      rate. We conducted a cross-sectional survey of inpatients discharged from
      medicine housestaff teams from 2008 to 2009. Patients identified providers by
      face, name, and role and stated their reason for hospitalization. The Hospital
      Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey assessed
      patient satisfaction with care. Eighty-nine of 95 patients (94%) participated.
      Seventy-five percent of patients recognized one provider face, 28% knew at least
      one provider name, and 21% correctly stated provider roles. Fifty-seven percent
      of patients knew their diagnosis. Satisfaction with care via HCAHPS varied: 78%
      always felt treated with courtesy and respect; 75% felt doctors always listened;
      and 67% felt complete involvement in care decisions. In bivariate and
      multivariate analyses, knowledge of providers by face, name, or role was not
      associated with knowledge of diagnosis, satisfaction, or 30-day readmission rates
      (all p>.05). Thus, patient recognition of providers was not associated with their
      knowledge, satisfaction, or readmission.

PMID- 22414021
TI  - Changes in cholesterol metabolism-related gene expression in peripheral blood
      mononuclear cells from Alzheimer patients.
AB  - BACKGROUND: Cholesterol homeostasis dysfunction has been reported to have role in
      the pathogenesis of Alzheimer disease (AD). Therefore, changes in cholesterol
      metabolism in blood components may help to develop new potential AD biomarkers.
      In this study changes in cholesterol metabolism-related gene expression genes
      were evaluated in peripheral blood mononuclear cells (PBMCs) from AD subjects,
      their first degree relatives (FDR) and two groups of age matched controls (C1 >
      80 years, C2 < 60 years). The expression of three genes related to APP processing
      was also determined. RESULTS: Results showed significantly different behavior (P
      = 0.000) in the expression of all analyzed genes among the 4 groups. An inverse
      correlation emerged between the age of controls and the propensity of their PBMCs
      to express selected genes. Moreover, when gene expression was evaluated in PBMCs
      from AD patients and compared with that of PBMCs from healthy subjects of the
      same age, LDL-R and APP mRNAs were most abundant in AD as compared C1 whereas
      SREBP-2 and particularly nCEH were present at much lower mRNA levels in AD-PBMCs.
      This study describes for the first time a differential expression profile of
      cholesterol and APP related genes in PBMCs from AD patients and their FDR.
      CONCLUSIONS: We suggest that the expressions of cholesterol homeostasis and APP
      processing related genes in PBMC could be proposed as possible biomarkers to
      evaluate AD risk. In addition, gene expression in PBMC could be also used for
      diagnosis and development of therapeutic strategies as well as for personalized
      prediction in clinical outcome of AD.

PMID- 22414022
TI  - Ca(2+) /calmodulin- dependent protein kinase II mediates transforming growth
      factor-beta-induced hepatic stellate cells proliferation but not in collagen
      alpha1(I) production.
AB  - AIM:   Hepatic stellate cells (HSC) are the major players in hepatic fibrosis. As
      a most potent mitogen, transforming growth factor-beta (TGF-beta) strongly
      activates HSC and increases intracellular Ca(2+)  concentration. Here, we
      assessed the potential role of Ca(2+) /calmodulin-dependent protein kinase II
      (CaMKII), a main downstream effector of the Ca(2+)  signal in liver fibrogenesis
      cascade. METHODS:   A human immortal HSC cell line, LX-2, and primary rat hepatic
      stellate cells were used in current study. CaMKII blockage and Akt inhibition
      were performed by KN-93/CaMKIIalpha siRNA and LY294002, respectively. HSC
      proliferation was detected by 5-bromodeoxyuridine incorporation assay. Real-time
      polymerase chain reaction, western blot and enzyme-linked immunosorbent assay
      were used to measure mRNA, cellular protein and protein in medium, respectively.
      Procollagen alpha1(I) expression was detected by immunocytochemistry. The role of
      CaMKII on TGF-beta/Smad-induced collagen alpha1(I) expression was determined by
      (CAGA)(12) -MLP luciferase activity assay. RESULTS:   TGF-beta dramatically
      increased CaMKII mRNA, and total and phosphorylated CaMKII expression. KN-93 and
      CaMKIIalpha siRNA suppressed TGF-beta-mediated HSC proliferation. CaMKII
      interruption blocked TGF-beta-elicited Akt activation. LY294002 arrested HSC
      proliferation and collagen alpha1(I) production but had no effect on CaMKII.
      Furthermore, CaMKII led to increased p21 and p27 expression. KN-93 and
      CaMKIIalpha siRNA inhibited TGF-beta-induced and basal collagen alpha1(I)
      production but had no effect on the activity of (CAGA)(12) -MLP luciferase in
      response to TGF-beta stimulation. CONCLUSION:   CaMKII is a pivotal signal in TGF
      beta-induced fibrogenic cascades by means of stimulating HSC proliferation, and
      involved in a basal collagen production. Therefore, CaMKII will be a potentially
      effective target in the development of therapeutic intervention strategies to
      attenuate hepatic fibrosis.

PMID- 22414023
TI  - Medical care costs associated with traumatic brain injury over the full spectrum
      of disease: a controlled population-based study.
AB  - Data on traumatic brain injury (TBI) economic outcomes are limited. We used
      Rochester Epidemiology Project (REP) resources to estimate long-term medical
      costs for clinically-confirmed incident TBI across the full range of severity
      after controlling for pre-existing conditions and co-occurring injuries. All
      Olmsted County, Minnesota, residents with diagnoses indicative of potential TBI
      from 1985-2000 (n=46,114) were identified, and a random sample (n=7175) was
      selected for medical record review to confirm case status, and to characterize as
      definite (moderate/severe), probable (mild), or possible (symptomatic) TBI. For
      each case, we identified one age- and sex-matched non-TBI control registered in
      REP in the same year (+/-1 year) as case's TBI. Cases with co-occurring non-head
      injuries were assessed for non-head-injury severity and assigned similar non-head
      injury-severity controls. The 1145 case/control pairs for 1988-2000 were followed
      until earliest death/emigration of either member for medical costs 12 months
      before and up to 6 years after baseline (i.e., injury date for cases and
      comparable dates for controls). Differences between case and control costs were
      stratified by TBI severity, as defined by evidence of brain injury; comparisons
      used Wilcoxon signed-rank plus multivariate modeling (adjusted for pre-baseline
      characteristics). From baseline until 6 years, each TBI category exhibited
      significant incremental costs. For definite and probable TBI, most incremental
      costs occurred within the first 6 months; significant long-term incremental
      medical costs were not apparent among 1-year survivors. By contrast, cost
      differences between possible TBI cases and controls were not as great within the
      first 6 months, but were substantial among 1-year survivors. Although mean
      incremental costs were highest for definite cases, probable and possible cases
      accounted for>90% of all TBI events and 66% of total incremental costs.
      Preventing probable and possible events might facilitate substantial reductions
      in TBI-associated medical care costs.

PMID- 22414024
TI  - Consensus structure elucidation combining GC/EI-MS, structure generation, and
      calculated properties.
AB  - This article explores consensus structure elucidation on the basis of GC/EI-MS,
      structure generation, and calculated properties for unknown compounds. Candidate
      structures were generated using the molecular formula and substructure
      information obtained from GC/EI-MS spectra. Calculated properties were then used
      to score candidates according to a consensus approach, rather than filtering or
      exclusion. Two mass spectral match calculations (MOLGEN-MS and MetFrag),
      retention behavior (Lee retention index/boiling point correlation, NIST Kovat's
      retention index), octanol-water partitioning behavior (log K(ow)), and finally
      steric energy calculations were used to select candidates. A simple consensus
      scoring function was developed and tested on two unknown spectra detected in a
      mutagenic subfraction of a water sample from the Elbe River using GC/EI-MS. The
      top candidates proposed using the consensus scoring technique were purchased and
      confirmed analytically using GC/EI-MS and LC/MS/MS. Although the compounds
      identified were not responsible for the sample mutagenicity, the structure
      generation-based identification for GC/EI-MS using calculated properties and
      consensus scoring was demonstrated to be applicable to real-world unknowns and
      suggests that the development of a similar strategy for multidimensional high
      resolution MS could improve the outcomes of environmental and metabolomics
      studies.

PMID- 22414025
TI  - The early implementation of Trypanosoma cruzi antibody screening of donors and
      donations within England: preempting a problem.
AB  - BACKGROUND: Trypanosoma cruzi is a parasitic infection endemic in Central and
      Southern America, but is spreading into nonendemic countries with migration of
      infected individuals from endemic countries. The parasite is transmitted by
      transfusion or transplantation and donation screening is performed routinely in
      endemic countries to prevent transmission. In situations where migrants from
      endemic countries have settled in nonendemic countries and present as donors
      (blood or other cellular products), intervention is required to prevent
      transfusion or transplantation transmission. STUDY DESIGN AND METHODS: A
      screening program for T. cruzi was developed and has been used successfully for
      over 10 years that includes donor selection and donation screening. Donor
      selection criteria to identify specific risk of T. cruzi infection were developed
      together with laboratory screening of donations for T. cruzi antibodies and the
      subsequent confirmation of screen reactivity. RESULTS: Since the introduction of
      T. cruzi screening in England in 1998, a total of 38,585 donors and donations
      have been screened for T. cruzi antibodies, of which 223 were repeat reactive on
      screening and referred for confirmation: 206 confirmed negative, 14 inconclusive,
      and three positive. Since the move in 2005 from donor qualification to donation
      release testing, 15,536 donations were collected and screened, of which 15,499
      (99.8%) were T. cruzi antibody negative and released to inventory. CONCLUSION: An
      effective program to minimize risk of the transmission of T. cruzi infection via
      donations has been developed and implemented. Not only does the program minimize
      risk of transmission, it also minimizes the cumulative, and needless, loss of
      donors and donations that would ensue if permanent donor deferral alone was
      adopted.

PMID- 22414026
TI  - Arterial pressure profile in patients with cirrhosis: Fourier analysis of
      arterial pulse in relation to pressure level, stroke volume, and severity of
      disease: on the reduction of afterload in the hyperdynamic syndrome.
AB  - OBJECTIVE: Patients with cirrhosis have cardiovascular dysfunction and altered
      mechanical properties of large and small arteries. This study was undertaken in
      order to analyze the arterial pressure curve in relation to mean arterial
      pressure level, stroke volume, and severity of liver disease. MATERIALS AND
      METHODS: Forty-one patients with cirrhosis (Child-Turcotte classes A/B/C =
      13/15/13) were studied during a hemodynamic investigation of portal hypertension.
      Fifteen patients without liver disease served as controls. We applied fast
      Fourier analysis to quantify the pressure components of the arterial curve, the
      harmonic Fourier coefficients (HFC). RESULTS: Mean arterial pressure was
      significantly reduced (91 vs. 98 mmHg, p < 0.001) and stroke volume was
      significantly increased (94 vs. 78 ml, p < 0.001) in patients with cirrhosis
      versus controls. The HFC were significantly lower in patients with cirrhosis than
      in controls (-15 to -24%, p < 0.002), except for the fourth HFC, which was
      significantly increased (+28%, p < 0.02). In contrast to controls, which showed a
      highly significant effect of the level of arterial pressure on their HFC (p <
      0.001), patients with cirrhosis did not show pressure or stroke volume dependence
      on their HFC, indicating an overall compliant and slow reflective arterial
      vascular bed. The initial rise in pulse pressure (dP/dt) was inversely related to
      the Child-Turcotte score (p < 0.05), and the HFC were borderline significantly
      related to this score (p = 0.07). CONCLUSIONS: The arterial pulsation in
      cirrhosis is qualitatively changed with reduced pulse reflections, which may
      protect against manifest cardiac failure in patients with advanced cirrhosis.

PMID- 22414027
TI  - Modulation of structure and dynamics by disulfide bond formation in unfolded
      states.
AB  - During oxidative folding, the formation of disulfide bonds has profound effects
      on guiding the protein folding pathway. Until now, comparatively little is known
      about the changes in the conformational dynamics in folding intermediates of
      proteins that contain only a subset of their native disulfide bonds. In this
      comprehensive study, we probe the conformational landscape of non-native states
      of lysozyme containing a single native disulfide bond utilizing nuclear magnetic
      resonance (NMR) spectroscopy, small-angle X-ray scattering (SAXS), circular
      dichroism (CD) data, and modeling approaches. The impact on conformational
      dynamics varies widely depending on the loop size of the single disulfide
      variants and deviates significantly from random coil predictions for both NMR and
      SAXS data. From these experiments, we conclude that the introduction of single
      disulfides spanning a large portion of the polypeptide chain shifts the structure
      and dynamics of hydrophobic core residues of the protein so that these regions
      exhibit levels of order comparable to the native state on the nanosecond time
      scale.

PMID- 22414028
TI  - Uterine cervical malignant granular cell tumor.
AB  - Malignant granular cell tumor is relatively uncommon, constituting only 1-2% of
      all granular cell tumors. It is a rare and unusual tumor, especially in non
      typical sites, such as the uterine cervix, and grows more rapidly than benign
      granular cell tumor. It can be treated with surgical excision, but recurrence is
      possible and prognosis can be poor. A malignant granular cell tumor in the
      uterine cervix of a 37-year-old woman was incidentally diagnosed. The patient has
      a history of irregular vaginal bleeding. Uterine cervical biopsy under colposcope
      revealed a malignant granular cell tumor. After isophosphamide, etoposide, and
      cisplatin neoadjuvant chemotherapy, surgery was performed on the lesion, which
      approximately involved half the depth of cervical stroma. Computed tomography
      examination showed no local recurrence or distant metastasis during the 26-month
      follow-up period.

PMID- 22414029
TI  - Congenital pulmonary airway malformation (CPAM) [congenital cystic adenomatoid
      malformation] associated with tracheoesophageal fistula and agensesis of the
      corpus callosum.
AB  - Congenital pulmonary airway malformations (CPAM) are a family of hamartomatous
      disorders due to the uncontrolled overgrowth of the terminal bronchioles.
      Congenital pulmonary airway malformations can co-exist with cardiovascular and/or
      urogenital malformations, but their association with thoracopulmonary
      malformations is extremely rare. We report the first case of CPAM type I, co
      existing with tracheo-esophageal fistula and corpus callosum agenesis.

PMID- 22414030
TI  - Neurocysticercosis in immigrant populations.

PMID- 22414031
TI  - Quality of travel health advice in a French travel medicine and vaccine center: a
      prospective observational study.
AB  - BACKGROUND: The number of international trips undertaken by French citizens is
      rising and we wished to assess the appropriateness of advices given to travelers
      in a vaccine and travel medicine center in France. METHODS: We conducted a 3
      month prospective study in one center in Paris where prescriptions and advice to
      travelers are given by trained physicians in travel medicine who have access to a
      computerized decision support system (Edisan). A questionnaire was used to record
      trip characteristics, patients' demographics, and prescriptions. Main outcome
      measure was the adequacy of prescriptions for malaria prophylaxis, yellow fever,
      and hepatitis A vaccines to French guidelines. RESULTS: A total of 730 subjects
      were enrolled in this study, with a median age of 28 years. Travel destinations
      were sub-Saharan Africa (58%), Asia (21%), and South America (18%). Among the 608
      patients (83%) traveling to malaria-endemic areas, malaria prophylaxis was in
      accordance with guidelines in 578/608 patients (95.1%, 95% CI: 93-96.5), and
      doxycycline was the regimen of choice (48%). Inappropriate malaria prophylaxis
      was given to eight patients, one of whom developed plasmodium falciparum malaria.
      All 413 patients (100%, 95% CI: 99-100) traveling to yellow fever-endemic areas
      who needed vaccination were correctly vaccinated. However, three patients
      received yellow fever vaccination without indication. Also, 442 of 454 patients
      (97.4%, 95% CI: 95.4-98.5) eligible to receive hepatitis A vaccination were
      immunized. CONCLUSION: Appropriate advice for malaria prophylaxis, yellow fever,
      and hepatitis A vaccinations was provided in a travel medicine and vaccine center
      where trained physicians used a computerized decision support system. Even in
      this setting, however, errors can occur and professional practices should be
      regularly assessed to improve health care.

PMID- 22414032
TI  - Evaluation of travel medicine practice by yellow fever vaccination centers in
      England, Wales, and Northern Ireland.
AB  - BACKGROUND: The National Travel Health Network and Centre (NaTHNaC) introduced a
      program of registration, training, standards, and audit for yellow fever
      vaccination centers (YFVCs) in England, Wales, and Northern Ireland (EWNI) in
      2005. Prior to rolling out the program, NaTHNaC surveyed YFVCs in England.
      OBJECTIVES: To reassess the practice of YFVCs in 2009, 4 years after the
      institution of the NaTHNaC program, to identify areas for ongoing support, and to
      assess the impact of the program. METHODS: In 2009, all YFVCs in EWNI were asked
      to complete a questionnaire on type of practice, administration of travel
      vaccines, staff training, vaccine storage and patient record keeping, use of
      travel health information, evaluation of NaTHNaC yellow fever (YF) training, and
      resource and training needs. Data were analyzed using Microsoft Excel(r) and
      STATA 9(r). RESULTS: The questionnaire was completed by 1,438 YFVCs (41.5% of
      3,465 YFVCs). Most YFVCs were based in General Practice (87.4%). In nearly all
      YFVCs (97.0%), nurses advised travelers and administered YF vaccine. An annual
      median of 50 doses of YF vaccine was given by each YFVC. A total of 96.7% of
      nurses had received training in travel medicine, often through study days run by
      vaccine manufacturers. The internet was frequently used for information during
      travel consultations (84.8%) and NaTHNaC's on-line and telephone advice resources
      were highly rated. Following YF training, 95.8% of attendees expressed improved
      confidence regarding YF vaccination issues. There was excellent adherence to
      vaccination standards: >= 94% correctly stored vaccines, recorded refrigerator
      temperatures, and maintained YF vaccination records. CONCLUSIONS: In the 4 years
      since institution of the NaTHNaC program for YFVCs, there has been improved
      adherence to basic standards of immunization practice and increased confidence of
      health professionals in YF vaccination. The NaTHNaC program could be a model for
      other national public health bodies, as they establish a program for YF centers.

PMID- 22414033
TI  - Travel and tropical medicine practice among infectious disease practitioners.
AB  - BACKGROUND: Infectious disease specialists who evaluate international travelers
      before or after their trips need skills to prevent, recognize, and treat an
      increasingly broad range of infectious diseases. Wide variation exists in
      training and percentage effort among providers of this care. In parallel, there
      may be variations in approach to pre-travel consultation and the types of travel
      related illness encountered. Aggregate information from travel-medicine providers
      may reveal practice patterns and novel trends in infectious illness acquired
      through travel. METHODS: The 1,265 members of the Infectious Disease Society of
      America's Emerging Infections Network were queried by electronic survey about
      their training in travel medicine, resources used, pre-travel consultations, and
      evaluation of ill-returning travelers. The survey also captured information on
      whether any of 10 particular conditions had been diagnosed among ill-returning
      travelers, and if these diagnoses were perceived to be changing in frequency.
      RESULTS: A majority of respondents (69%) provided both pre-travel counseling and
      post-travel evaluations, with significant variation in the numbers of such
      consultations. A majority of all respondents (61%) reported inadequate training
      in travel medicine during their fellowship years. However, a majority of recent
      graduates (55%) reported adequate preparation. Diagnoses of malaria, traveler's
      diarrhea, and typhoid fever were reported by the most respondents (84, 71, and
      53%, respectively). CONCLUSIONS: The percent effort dedicated to pre-travel
      evaluation and care of the ill-returning traveler vary widely among infectious
      disease specialists, although a majority participate in these activities. On the
      basis of respondents' self-assessment, recent fellowship training is reported to
      equip graduates with better skills in these areas than more remote training.
      Ongoing monitoring of epidemiologic trends of travel-related illness is
      warranted.

PMID- 22414034
TI  - Deaths in international travelers arriving in the United States, July 1, 2005 to
      June 30, 2008.
AB  - BACKGROUND: The Centers for Disease Control and Prevention's (CDC) Quarantine
      Activity Reporting System (QARS), which documents reports of morbidity and
      mortality among travelers, was analyzed to describe the epidemiology of deaths
      during international travel. METHODS: We analyzed travel-related deaths reported
      to CDC from July 1, 2005 to June 30, 2008, in which international travelers died
      (1) on a U.S.-bound conveyance, or (2) within 72 hours after arriving in the
      United States, or (3) at any time after arriving in the United States from an
      illness possibly acquired during international travel. We analyzed age, sex, mode
      of travel (eg, by air, sea, land), date, and cause of death, and estimated rates
      using generalized linear models. RESULTS: We identified 213 deaths. The median
      age of deceased travelers was 66 years (range 1-95); 65% were male. Most deaths
      (62%) were associated with sea travel; of these, 111 (85%) occurred in cruise
      ship passengers and 20 (15%) among cargo and cruise ship crew members. Of 81 air
      travel-associated deaths, 77 occurred in passengers, 3 among air ambulance
      patients, and 1 in a stowaway. One death was associated with land travel. Deaths
      were categorized as cardiovascular (70%), infectious disease (12%), cancer (6%),
      unintentional injury (4%), intentional injury (1%), and other (7%). Of 145
      cardiovascular deaths with reported ages, 62% were in persons 65 years of age and
      older. Nineteen (73%) of 26 persons who died from infectious diseases had chronic
      medical conditions. There was significant seasonal variation (lowest in July
      September) in cardiovascular mortality in cruise ship passengers. CONCLUSIONS:
      Cardiovascular conditions were the major cause of death for both sexes. Travelers
      should seek pre-travel medical consultation, including guidance on preventing
      cardiovascular events, infections, and injuries. Persons with chronic medical
      conditions and the elderly should promptly seek medical care if they become ill
      during travel.

PMID- 22414035
TI  - Health risks of travelers with medical conditions--a retrospective analysis.
AB  - BACKGROUND: Traveling the world may result in infection with tropical or other
      travel-associated diseases. This applies increasingly also to people with immune
      compromising and other medical conditions, as well as to elderly individuals. To
      reduce exposure and susceptibility to health risks, there is a need for
      appropriate pre-travel advice for these particular groups of travelers. METHODS:
      In this observational study, we analyzed the overall risk of health problems
      among travelers with underlying medical conditions who attended the University of
      Amsterdam's Academic Medical Center's (AMC) travel clinic from January to October
      2010. Telephone questionnaires were administered to 345 travelers with underlying
      conditions and 100 healthy travelers. RESULTS: The most common underlying medical
      conditions studied included: (1) diabetes mellitus; (2) impaired immunity due to
      use of immune-suppressing medication; (3) reduced gastric barrier; and (4) HIV
      infection. The overall incidence of travel-related diseases (TRDs) was higher
      among those patients with underlying medical conditions compared to healthy
      travelers [incidence rate ratio (IRR) 2.26, 95% CI (1.29-3.98)]. Of all diseases
      reported, gastrointestinal disease, fever, and respiratory problems were reported
      most frequently. Travel to Central America, South Central Asia, Northeast Asia,
      and North Africa was associated with increased risk of contracting TRD. Hepatitis
      B protection was absent or unknown in 75% of these travelers. CONCLUSIONS:
      Travelers with medical conditions had a higher risk of obtaining TRD,
      predominantly gastrointestinal in nature.

PMID- 22414036
TI  - Neurocysticercosis among international travelers to disease-endemic areas.
AB  - OBJECTIVE: Review of neurocysticercosis in citizens from non-endemic countries
      who developed the disease after a travel to endemic regions, to estimate the
      magnitude of the disease and to determine the pattern of disease expression in
      travelers to disease-endemic areas. METHODS: MEDLINE and manual search of
      international travelers with neurocysticercosis diagnosed in countries where the
      disease is not endemic, from 1981 to October 2011. Abstracted data included:
      demographic profile of patients, clinical manifestations, form of
      neurocysticercosis, and therapy. RESULTS: A total of 35 articles reporting 52
      patients were found. Most patients were originally from Western Europe,
      Australia, Israel, and Japan. Mean age was 36.5 +/- 15.1 years, and 46% were
      women. Common places for travelling were the Indian Subcontinent, Latin America,
      and Southeast Asia. Mean time spent aboard was 56.6 +/- 56.1 months. Most
      patients developed symptoms 2 years or more after returning home. Seizures were
      the most common clinical manifestation of the disease (73%), and all but six
      patients had parenchymal brain cysticercosis (a single cysticercus granuloma was
      the most common neuroimaging finding, in 21 patients). Twenty patients underwent
      surgical resection of the brain lesion for diagnostic purposes, and 22 received
      cysticidal drugs. CONCLUSIONS: Neurocysticercosis is rare in international
      travelers to endemic countries, and most often occurs in long-term travelers. It
      is possible that most of these patients get infected by contact with a taenia
      carrier. The time elapsed between disease acquisition and symptoms occurrence
      suggests that, at least in some patients, clinical manifestations are related to
      reactivation of an infection that has previously been controlled by the host
      immune system.

PMID- 22414037
TI  - Neurocysticercosis among resettled refugees from Burma.
AB  - Taenia solium is the most common helminthic infection of the central nervous
      system and a leading cause of epilepsy in developing nations. Little is known
      about neurocysticercosis in refugees from Southeast Asia which is endemic for T
      solium. We present two cases in a single household of refugees from Burma.

PMID- 22414038
TI  - Lack of interference by zoster vaccine with the immune response to yellow fever
      vaccine.
AB  - Concerns exist about the serologic response to yellow fever (YF) vaccine when
      given within 28 days of another live virus vaccine. We report the case of a
      healthy adult who received 17D YF vaccine 21 days following administration of
      another live viral vaccine, and developed a protective level of immunity against
      YF virus.

PMID- 22414039
TI  - Successful treatment of imported mucosal Leishmania infantum leishmaniasis with
      miltefosine after severe hypokalemia under meglumine antimoniate treatment.
AB  - Old World mucosal leishmaniasis is a rare but regularly reported disease in
      Southern Europe. We report the case of a 64-year-old woman who developed severe
      hypokalemia under meglumine antimoniate treatment and was successfully treated
      under second line therapy with miltefosine.

PMID- 22414040
TI  - A case of Japanese encephalitis virus infection acquired during a trip in
      Thailand.
AB  - A case of Japanese encephalitis virus (JEV) infection is reported in a young
      traveler returning from Thailand. Clinical suspicion of JEV in travelers
      returning from endemic areas with neurologic symptoms is warranted. Confirmation
      of the diagnosis is complex and requires specialized laboratory services.
      Individualized advice on the costs and benefits of vaccination is recommended.

PMID- 22414041
TI  - Travel reported by pilgrims from Marseille, France before and after the 2010
      Hajj.
AB  - Sixty-seven percent of French pilgrims reported to have traveled out of France
      just before the 2010 Hajj (mainly in North Africa) and 26% planned to do so after
      leaving Saudi Arabia. Surveillance of Hajj-associated infectious diseases in
      returned French pilgrims should be coordinated between France and North African
      countries.

PMID- 22414042
TI  - Uncommon manifestation of a mixed-species malaria infection: cryptic falciparum
      malaria in a traveler with successfully treated tertian malaria.
AB  - We report a case of falciparum malaria in a traveler 9 days after successful
      treatment of ovale malaria. The underlying, cryptic mixed-species infection was
      primarily undetectable with standard laboratory diagnostics. This case highlights
      the limitations of these tests and the unpredictability of typical incubation
      periods in the individual case.

PMID- 22414043
TI  - Preexposure rabies vaccination schedule.

PMID- 22414045
TI  - Using the method of judgement analysis to address variations in diagnostic
      decision making.
AB  - BACKGROUND: Heart failure is not a clear-cut diagnosis but a complex clinical
      syndrome with consequent diagnostic uncertainty. Judgment analysis is a method to
      help clinical teams to understand how they make complex decisions. The method of
      judgment analysis was used to determine the factors that influence clinicians'
      diagnostic decisions about heart failure. METHODS: Three consultants, three
      middle grade doctors, and two junior doctors each evaluated 45 patient scenarios.
      The main outcomes were: clinicians' decisions whether or not to make a diagnosis
      of suspected heart failure; the relative importance of key factors within and
      between clinician groups in making these decisions, and the acceptability of the
      scenarios. RESULTS: The method was able to discriminate between important and
      unimportant factors in clinicians' diagnostic decisions. Junior and consultant
      physicians tended to use patient information similarly, although junior doctors
      placed particular weight on the chest X-Ray. Middle-grade doctors tended to use
      information differently but their diagnostic decisions agreed with consultants
      more frequently (k = 0.47) than junior doctors and consultants (k = 0.23), or
      middle grade and junior grade doctors (k = 0.10). CONCLUSIONS: Judgment analysis
      is a potentially valuable method to assess influences upon diagnostic decisions,
      helping clinicians to manage the quality assurance process through evaluation of
      care and continuing professional development.

PMID- 22414046
TI  - Effect of dentin pre-treatment with a casein phosphopeptide-amorphous calcium
      phosphate (CPP-ACP) paste on dentin bond strength in tridimensional cavities.
AB  - OBJECTIVE: This study aimed to evaluate the push-out bond strength of
      dimethacrylate (Clearfil SE Bond/Filtek Z250; and Adper SE Plus/Filtek Z250) and
      silorane-based (Filtek P90 adhesive system/Filtek P90 composite resin)
      restorative systems following selective dentin pre-treatment with a CPP-ACP
      containing paste (MI Paste). MATERIALS AND METHODS: Sixty bovine incisors were
      utilized. The buccal surface was wet-ground to obtain a flat dentin area.
      Standardized conical cavities were then prepared. Adhesive systems were applied
      according to manufacturers' directions and the composites were bulk-inserted into
      the cavity. The push-out bond strength test was performed at a universal testing
      machine (0.5 mm/min) until failure; failure modes were analyzed by scanning
      electron microscopy. Data were analyzed by two-way ANOVA and Tukey post-hoc test
      (p < 0.05). RESULTS: For Clearfil SE Bond/Filtek Z250 and Filtek P90 adhesive
      system/Filtek P90 composite resin, the dentin pre-treatment did not influence
      bond strength means. For Adper SE Plus/Filtek Z250, dentin samples treated with
      MI Paste had statistically higher bond strength means than non-treated specimens.
      Adhesive failures were more frequent. CONCLUSION: Dentin pre-treatment with the
      CPP-ACP containing paste did not negatively affect bond strength for Clearfil SE
      Bond/Filtek Z250 and Filtek P90 adhesive system/Filtek P90 composite resin
      restorative systems and improved bond strength for the Adper SE Plus/Filtek Z250
      restorative system.

PMID- 22414047
TI  - Gold nanoparticle-induced formation of artificial protein capsids.
AB  - Gold nanoparticles are generally considered to be biologically inactive. However,
      in this study we show that the addition of 1.4 nm diameter gold nanoparticle
      induces the remodeling of the ring-shaped protein TRAP into a hollow, capsid-like
      configuration. This structural remodeling is dependent upon the presence of
      cysteine residues on the TRAP surface as well as the specific type of gold
      nanoparticle. The results reveal an apparent novel catalytic role of gold
      nanoparticles.

PMID- 22414048
TI  - Anti-inflammatory effects of methoxyphenolic compounds on human airway cells.
AB  - BACKGROUND: The respiratory epithelium plays a central role in the inflammatory
      response in asthma and other diseases. Methoxyphenolic compounds are purported to
      be effective anti-inflammatory agents, but their effects on the airway epithelium
      have not been well characterized. METHODS: Human airway cells were stimulated
      with TNF-alpha in the presence or absence of 4-substituted methoxyphenols and
      resveratrol. The expression of various cytokines was measured by qPCR, ELISAs,
      and protein arrays. Reactive oxygen species (ROS) production was measured with a
      reactive fluorescent probe (3',6'-diacetate-2',7'-dichlorofluorescein).
      Activation of NF-kappaB was measured by nuclear translocation and
      phosphorylation. Ribonuclear protein association with mRNA was assessed with a
      biotin-RNA affinity isolation assay. RESULTS: Multiple inflammatory mediators
      were inhibited by methoxyphenols, including: CCL2, CCL5, IL-6, IL-8, ICAM-1, MIF,
      CXCL1, CXCL10, and Serpin E1. IC50 values were obtained for each compound that
      showed significant anti-inflammatory activity: diapocynin (20.3 MUM), resveratrol
      (42.7 MUM), 2-methoxyhydroquinone (64.3 MUM), apocynin (146.6 MUM), and 4-amino-2
      methoxyphenol (410 MUM). The anti-inflammatory activity did not correlate with
      inhibition of reactive oxygen species production or NF-kappaB activation.
      However, methoxyphenols inhibited binding of the RNA-binding protein HuR to mRNA,
      indicating that they may act post-transcriptionally. CONCLUSIONS: Methoxyphenols
      demonstrate anti-inflammatory activity in human airway cells. More potent
      compounds that act via similar mechanisms may have therapeutic potential as novel
      anti-inflammatory agents.

PMID- 22414049
TI  - Chinese Americans' views of prenatal genetic testing in the genomic era: a
      qualitative study.
AB  - Prenatal genetic testing (PGT) for early and accurate diagnosis of complex
      genomic diseases and traits, along with relatively rare and severe genetic
      disorders, is a growing trend in genomic medicine. To address the ethical, legal,
      and social issues regarding PGT use, the voices of racial/ethnic minorities
      should be heard. This first-of-its-kind qualitative study examined Chinese
      Americans' perspectives regarding PGT to diagnose their fetuses for various
      genetic/genomic diseases and traits. We conducted semi-structural, hypothetical
      scenario-based interviews with 49 participants from two major Chinese-American
      communities in the South. Although approximately one fifth of participants
      refused to test their fetuses, most tended to favor PGT. The four most frequently
      identified diseases/traits mentioned by participants included family-history
      related diseases, genetic disorders, intelligence quotient (IQ), and
      psychological/mental disorders. A few respondents, regardless of socio
      demographic status, indicated they might terminate their pregnancies if their
      fetuses carried genes for family-history-related diseases, genetic disorders, low
      IQ, psychological/mental disorders, and/or physical defects. Participants'
      attitudes might reflect lack of genetic/genomic knowledge and unawareness of
      available resources for families with special needs. Moreover, some participants'
      attitudes appeared related to their cultural beliefs. Our findings represent an
      initial window to understand Chinese Americans' views regarding PGT. Additional
      quantitative studies on large samples are needed.

PMID- 22414050
TI  - Effects of interferon therapy on development of hepatocellular carcinoma in
      patients with hepatitis C-related cirrhosis: A meta-analysis of randomized
      controlled trials.
AB  - AIM:   The role of interferon (IFN) therapy on prevention of hepatocellular
      carcinoma (HCC) in patients with hepatitis C virus (HCV)-related cirrhosis
      remains controversial. This meta-analysis aimed to determine whether IFN therapy
      reduced the incidence of HCC in HCV-related cirrhotic patients. METHODS:   We
      performed a meta-analysis including eight randomized controlled trials (RCT) (a
      total of 1505 patients) to assess the effect of IFN therapy on prevention of HCC
      in patients with HCV-related cirrhosis. The pooled odds ratios (OR) were
      calculated using a random or fixed effects model. RESULTS:   Our results showed
      that IFN therapy significantly decreased the overall HCC incidence in HCV-related
      cirrhotic patients (OR, 0.29; 95% confidence interval [CI], 0.10-0.80; P = 0.02).
      HCC risk in patients who failed to achieve sustained virological response (SVR)
      in the initial IFN-based treatment was also reduced by maintenance IFN therapy
      (OR, 0.54; 95% CI, 0.32-0.90; P = 0.02). Subgroup analysis indicated that IFN
      therapy decreased HCC incidence in HCV-related cirrhotic patients during long
      term follow up (>48 months) evidently (OR, 0.25; 95% CI, 0.09-0.67; P = 0.006).
      However, subgroup analysis of four RCT with short-term follow up (<=48 months)
      did not demonstrate the significant difference in HCC incidence between IFN
      treated cirrhotic patients and controls (OR, 0.78; 95% CI, 0.39-1.55; P = 0.48).
      CONCLUSION:   The present study suggested that IFN therapy could efficiently
      reduce HCC development in patients with HCV-related cirrhosis; this effect was
      more evident in the subgroup of patients with long-term follow up (>48 months).
      Patients who received maintenance IFN therapy had a lower risk of HCC than
      controls.

PMID- 22414051
TI  - Characterization of multifunctional nanosystems based on the avidin-nucleic acid
      interaction as signal enhancers in immuno-detection.
AB  - The Avidin-Nucleic-Acids-Nano-Assembly (ANANAS) is a kind of soft poly avidin
      nanoparticle originating from the high affinity interaction between avidin and
      the nucleic acids. In this work we investigated the possibility of transforming
      ANANAS cores into stoichiometrically controlled multifunctional nanoparticles
      through a "one-pot" procedure, and we measured in a quantitative way their
      ability to work as reagents for enhanced immunodiagnostic detection. Initially,
      we measured the ANANAS loading capability for biotinylated proteins of different
      nature. About 200 molecules of biotin-horseradish-peroxidase (40KDa b-HRP) and 60
      molecules of biotin-immunoglobulin-G (150KDa b-IgG) could be accommodated onto
      each nanoparticle, showing that steric limitations dictate the number of loadable
      entities. Stoichiometrically controlled functional assemblies were generated by
      mixing core particles with subsaturating amounts of b-HRP and b-IgG. When applied
      as detection reagents in an Enzyme-Linked-ImmunoSorbed-Assay (ELISA), these
      assemblies were up to two-orders of magnitude more sensitive than commercial HRP
      based reagents. Assemblies of different composition displayed different efficacy,
      indicating that the system functionality can be fine-tuned. Within-assay
      variability (CV%), measured to assess if the assembly procedure is reproducible,
      was within 10%. Stability experiments demonstrated that the functionalyzed
      assemblies are stable in solution for more than one week. In principle, any
      biotinylated function can be loaded onto the core particle, whose high loading
      capacity and tunability may open the way toward further application in
      biomedicine.

PMID- 22414052
TI  - Coordination and metalation bifunctionality of Cu with 5,10,15,20-tetra(4
      pyridyl)porphyrin: toward a mixed-valence two-dimensional coordination network.
AB  - We investigated the coordination self-assembly and metalation reaction of Cu with
      5,10,15,20-tetra(4-pyridyl)porphyrin (2HTPyP) on a Au(111) surface by means of
      scanning tunneling microscopy, X-ray photoelectron spectroscopy, and density
      functional theory calculations. 2HTPyP was found to interact with Cu through both
      the peripheral pyridyl groups and the porphyrin core. Pairs of pyridyl groups
      from neighboring molecules coordinate Cu(0) atoms, which leads to the formation
      of a supramolecular metal-organic coordination network. The network formation
      occurs at room temperature; annealing at 450 K enhances the process. The
      interaction of Cu with the porphyrin core is more complex. At room temperature,
      formation of an initial complex Cu(0)-2HTPyP is observed. Annealing at 450 K
      activates an intramolecular redox reaction, by which the coordinated Cu(0) is
      oxidized to Cu(II) and the complex Cu(II)TPyP is formed. The coordination network
      consists then of Cu(II) complexes linked by Cu(0) atoms; that is, it represents a
      mixed-valence two-dimensional coordination network consisting of an ordered array
      of Cu(II) and Cu(0) centers. Above 520 K, the network degrades and the Cu atoms
      in the linking positions diffuse into the substrate, while the Cu(II)TPyP
      complexes form a close-packed structure that is stabilized by weak intermolecular
      interactions. Density functional theory investigations show that the reaction
      with Cu(0) proceeds via formation of an initial complex between metal atom and
      porphyrin followed by formation of Cu(II) porphyrin within the course of the
      reaction. The activation barrier of the rate limiting step was found to be 24-37
      kcal mol(-1) depending on the method used. In addition, linear coordination of a
      Cu atom by two CuTPyP molecules is favorable according to gas-phase calculations.

PMID- 22414053
TI  - Early ERCP and biliary sphincterotomy with or without small-caliber pancreatic
      stent insertion in patients with acute biliary pancreatitis: better overall
      outcome with adequate pancreatic drainage.
AB  - OBJECTIVE: To analyze the efficacy of pancreatic duct (PD) stenting following
      endoscopic sphincterotomy (EST) compared with EST alone in reducing complication
      rate and improving overall outcome in acute biliary pancreatitis (ABP). METHODS:
      Between 1 January 2009 and 1 July 2010, 141 nonalcoholic patients with clinical,
      laboratory and imaging evidence of ABP were enrolled. Emergency endoscopic
      retrograde cholangiopancreatography (ERCP) was performed within 72 h from the
      onset of pain. Seventy patients underwent successful ERCP, EST, and stone
      extraction (control group); 71 patients (PD stent group) had EST, stone
      extraction and small-caliber (5 Fr, 3-5 cm) pancreatic stent insertion. All
      patients were hospitalized for medical therapy and jejunal feeding and were
      followed up. RESULTS: The mean age, Glasgow score, symptom to ERCP time, mean
      amylase and CRP levels at initial presentation were not significantly different
      in the PD stent group compared to the control group: 60.6 vs. 64.3, 3.21 vs.
      3.27, 34.4 vs. 40.2, 2446.9 vs. 2114.3, 121.1 vs. 152.4, respectively.
      Complications (admission to intensive care unit, pancreatic necrosis with
      septicemia, large (>6 cm) pseudocyst formation, need for surgical necrosectomy)
      were less frequent in the PD stent group resulting in a significantly lower
      overall complication rate (9.86% vs. 31.43%, p < 0.002). Mortality rates (0% vs.
      4.28%) were comparable, reasonably low and without any significant differences.
      CONCLUSIONS: Temporary small-caliber PD stent placement may offer sufficient
      drainage to reverse the process of ABP. Combined with EST the process results in
      a significantly less complication rate and better clinical outcome compared with
      EST alone during the early course of ABP.

PMID- 22414054
TI  - Determination of neutrophil antigen HNA-3a and HNA-3b genotype frequencies in six
      racial groups by high-throughput 5' exonuclease assay.
AB  - BACKGROUND: People with the human neutrophil antigen (HNA)-3b/3b type can make
      HNA-3a antibodies, which have been reported to cause immune neutropenia disorders
      and are especially prone to cause severe cases of transfusion-related acute lung
      injury. However, knowledge of HNA-3 allele frequencies outside Caucasian
      populations is limited. We developed a high-throughput genotyping assay and
      determined the HNA-3a/3b genotype frequencies in six different racial and ethnic
      groups. STUDY DESIGN AND METHODS: Genotyping utilized TaqMan 5' exonuclease
      chemistry and real-time polymerase chain reaction. A total of 742 DNA samples
      from six different racial and ethnic groups were genotyped for HNA-3a and HNA-3b.
      RESULTS: The genotyping assay showed 100% sensitivity and specificity compared to
      sequencing and phenotyping and had high throughput. A significant percentage of
      Caucasians (6.5%), Han Chinese (16%), and Asian Indians (6%) typed HNA-3b/3b, but
      only a small percentage of Hispanics (1%) and no African or Native Americans.
      CONCLUSIONS: The HNA-3 genotyping assay had high sensitivity, specificity, and
      sample throughput. HNA-3b/b genotype results determined for 742 individuals
      representing six different racial and ethnic groups showed that there could be a
      significant risk of producing anti-HNA-3a in Chinese, as well as in Caucasian and
      Asian Indian blood donor populations, but a very low risk in Hispanic, African,
      or Native American populations.

PMID- 22414056
TI  - Dietary fatty acids in metabolic syndrome, diabetes and cardiovascular diseases.
AB  - In the last few decades, the prevalence of overweight and essential obesity has
      been undergoing a fast and progressive worldwide increase. Obesity has been in
      turn linked to type II diabetes, with the total number of diabetic patients
      worryingly increasing, in the last fifteen years, suggesting a pandemic
      phenomenon. At the same time, an increase in the prevalence of cardiovascular
      diseases has been also recorded. Increasing evidence suggests that the diet is
      involved in such escalation. In particular, the progressive globalization of food
      industry allowed massive supply, at a relatively low price, of a great variety of
      pre-packed food and bakery products, with very high energy content. Most of this
      food contains high amounts of saturated fatty acids (SFA) and of hydrogenated or
      trans fatty acids (TFA), that probably represent the prominent risk factors in
      the diet. Herein we will report diffusion and possible impact on health of such
      molecules, with reference to coronary heart disease, insulin resistance,
      metabolic syndrome and diabetes. We will also discuss the cellular and molecular
      mechanisms of action of fatty acids and fatty acid-derivatives which have been
      involved either in promoting or in preventing human pathologies. Free fatty acids
      (FFA) are not indeed only essential fuels for the organism. They also act as
      ligands for both membrane and nuclear receptors involved in different signaling
      pathways. Notably, some of these pathways can induce cell stress and apoptosis.
      Most important, FFA can affect glucose-induced insulin secretion and activate
      beta-cell death. These events can be at least in part counteracted by
      polyunsaturated fatty acids.

PMID- 22414057
TI  - Role of vitamin D in the pathophysiology and treatment of type 2 diabetes.
AB  - The secosteroid vitamin D is best known for its role in calcium regulation and
      bone metabolism. Recently, however, an emerging body of evidence has suggested
      that vitamin D may have previously-unrecognized effects on a variety of
      physiologic processes, including those relating to glucose homeostasis. Indeed,
      vitamin D insufficiency has been linked with type 2 diabetes (T2DM). In this
      review, the potential association between vitamin D and T2DM will be evaluated
      from both a pathophysiologic and clinical perspective. We consider the biologic
      evidence in support of a mechanistic contribution of vitamin D insufficiency to
      insulin resistance and beta-cell dysfunction, the two main pathophysiologic
      defects underlying T2DM. We also evaluate the clinical data linking vitamin D
      with these metabolic defects and dysglycemia. Finally, interventional studies
      addressing the effect of vitamin D supplementation on glucose homeostasis are
      considered. At present, this evolving literature is marked by many conflicting
      results and methodologic limitations, such that definitive conclusion on the role
      of vitamin D in T2DM remains elusive. Nevertheless, in light of the widespread
      prevalence of both vitamin D insufficiency and T2DM, this potential relationship
      could hold enormous public health implications and hence demands further study to
      address its unresolved questions.

PMID- 22414058
TI  - Non-invasive methods of glucose measurement: current status and future
      perspectives.
AB  - Diabetes mellitus (DM) is a very common disease which, if a good glycemic control
      is not achieved, can lead to serious chronic complications such as cardiovascular
      disease, retinopathy, nephropathy and neuropathy. Selfmonitoring of blood glucose
      is a fundamental tool for the proper adjustment of the treatment of diabetes and,
      at present, it is based mainly on capillary blood obtained by finger-prick (the
      classical glucometers). Since this method is painful and the strips are
      expensive, investigators have been attracted by the idea of using a non-invasive
      device for determining blood glucose which would permit more frequent testing and
      a tighter control of diabetes. The non-invasive measurement of blood glucose is
      based on the ability of the glucose molecule to interact with various chemical or
      physical methods. Nevetheless, in spite of some encouraging results and the
      efforts made over the past 30-40 years, there is no device available at present
      for use in clinical practice. A possible explanation might be the combination
      between the specific features of each method and the specific characteristics of
      diabetic patients, which make them respond differently to physical and chemical
      methods when compared to their healthy counterparts. In this paper we will give
      an overview of the noninvasive devices tested so far and their implications for
      the clinical management of the diabetic patient.

PMID- 22414060
TI  - Synthesizing the tetracyclic core of nanolobatolide.
AB  - A concise synthetic pathway that enables the stereoselective construction of the
      tetracyclic core of nanolobatolide has been developed by applying a tandem ring
      closing metathesis (RCM) reaction of dienynes, a Eu(fod)(3)-catalyzed
      intermolecular Diels-Alder reaction, and a biomimetic epoxide opening reaction as
      key steps.

PMID- 22414059
TI  - The role of peroxidation of mitochondrial membrane phospholipids in pancreatic
      beta -cell failure.
AB  - Type 2 diabetes (T2D) is characterized by peripheral insulin resistance and
      pancreatic islet beta-cell failure. Accumulating evidence indicates that
      mitochondrial dysfunction is a central contributor to beta-cell failure in the
      pathogenesis of T2D. This review focuses on mechanisms whereby reactive oxygen
      species (ROS) produced by beta-cell in response to metabolic stress affect
      mitochondrial structure and function and lead to beta-cell failure. Specifically,
      ROS oxidize mitochondrial membrane phospholipids such as cardiolipin, which
      impairs membrane integrity and leads to cytochrome c release and apoptosis. In
      addition, ROS activate UCP2 via peroxidation of the mitochondrial membrane
      phospholipids, which results in proton leak leading to reduced ATP synthesis and
      content in beta-cells - critical parameters in the regulation of glucose
      stimulated insulin secretion. Group VIA Phospholipase A2 (iPLA2beta) appears to
      be a component of a mechanism for repairing mitochondrial phospholipids that
      contain oxidized fatty acid substituents, and genetic or acquired iPLA2beta
      deficiency increases beta-cell mitochondrial susceptibility to injury from ROS
      and predisposes to development of T2D. Interventions that attenuate the adverse
      effects of ROS on beta-cell mitochondrial phospholipids may prevent or retard the
      development of T2D.

PMID- 22414061
TI  - External hemipelvectomy as treatment for solitary coxofemoral metastasis from
      endometrial carcinoma: case report and review of the literature.
AB  - The best treatment for bone metastasis from endometrial cancer as a presenting
      feature is unclear. We report the first case in the literature of coxofemoral
      metastases from endometrial cancer treated by surgical approach. Then, after a
      careful review of the literature, we discuss the best therapeutic option for this
      subset of patients. A 62-year-old woman with pain, erythema and swelling of the
      left leg and no history of postmenopausal bleeding underwent biopsy of the leg,
      which revealed a moderately differentiated endometrial carcinoma, infiltrating
      muscle and adipose tissues. There were no other sites of distal spread. A
      literature review was conducted by searching the items 'endometrial cancer' and
      'bone metastasis' in MEDLINE and EnBase up to September 2010. The patient was
      treated with neoadjuvant chemotherapy, but she did not show a clinical response.
      By considering her prognosis and quality of life, we decided to perform for the
      first time a total abdominal hysterectomy with bilateral salpingo-oophorectomy in
      addition to an external hemipelvectomy with a limb amputation and partial ilium
      and pubic preservation. Thirty months after the procedure the patient is still
      alive. No other similar results are present in the literature. Patients in good
      clinical condition with a single bone metastasis of endometrial cancer should be
      treated aggressively with surgery, as survival can be extended with an acceptable
      quality of life.

PMID- 22414062
TI  - Discordant Streptococcus agalactiae (Group B streptococcus) gestational infection
      in monochorionic/diamniotic and dichorionic/diamniotic twins.
AB  - Infection due to Streptococcus agalactiae or Group B streptococcus may be
      acquired during parturition or gestation. Discordant twin gestational Group B
      streptococcus infections are rarely reported. We describe two cases of fatal
      discordant gestational Group B streptococcus infection in both a
      monochorionic/diamniotic pregnancy and in a dichorionic/diamniotic pregnancy. In
      both instances, cultures, examination of the placentae, and autopsy findings
      demonstrated infection by Group B streptococcus in only the presenting fetus.
      Despite the ubiquity of this organism, this is the first documented case of
      discordant gestational Group B streptococcus infection in
      monochorionic/diamniotic twins and only the third case documented in
      dichorionic/diamniotic twins.

PMID- 22414063
TI  - Purification of the COP9 signalosome complex and binding partners from human T
      cells.
AB  - The COP9 Signalosome (CSN) is a highly conserved eight subunit protein complex
      associated with a wide range of essential biological functions in eukaryotic
      cells, and directly involved in processes including deneddylation,
      phosphorylation, and ubiquitination. Despite its significant role, very few
      studies have been undertaken to reveal the interactions between the CSN and its
      binding partners, and none in human T cells. Here we present a purification
      method for the CSN and binding proteins via the Streptavidin-Binding Peptide
      (SBP) fused to CSN Subunit 1 (CSN1). Using this method, coupled with liquid
      chromatography-mass spectrometry analysis, we identified all eight subunits of
      the CSN, as well as expected and putative novel binding partners such as a tumor
      suppressor under the control of Cullin4a-ligase complex; Neurofibromin 2
      (Merlin). This work presents a method for fast, reliable, and specific affinity
      based purification of a protein complex from a nonadherent cell line. The
      purification of the CSN and binding partners from T cells can elucidate the roles
      of CSN in a cell type where it has never been studied before. This proteomic
      based approach can broaden our understanding of the functions of the CSN in
      contexts such as viral-host interactions or immune activation in their natural
      milieu.

PMID- 22414064
TI  - Diffusion of chlorin-p6 across phosphatidyl choline liposome bilayer probed by
      second harmonic generation.
AB  - We have investigated the diffusion of the photosensitizer Chlorin-p(6) (Cp(6))
      across a egg lecithin lipid bilayer at different pH by the Second Harmonic
      Generation (SHG) method. Cp(6) has three ionizable carboxylic acid groups, and
      consequently, neutral and several ionic forms of Cp(6) are expected to be present
      in the pH range 3-8. The absorption spectra of Cp(6) get considerably modified in
      the presence of liposomes as the pH is decreased indicating that the drug
      liposome binding is pH dependent. The first pK(a) of interconversion (D-C) has
      been identified at pH ~7.0 by fluorescence measurement in an earlier work. In
      this work, the second pK(a) of interconversion (C-B) has been identified at pH
      ~4.8 by the hyper-Rayleigh scattering method. At acidic pH (3, 4, and 5), where
      species A, B, and C are dominant, the addition of liposomes to a Cp(6) solution
      generates an instantaneous rise (less than 1 s) in the second harmonic (SH)
      signal followed by decays whose time constants ranged from ten to hundreds of
      seconds. The instantaneous rise is attributed to the adsorption of Cp(6) to the
      outer lipid bilayer, and the decay is attributed to the diffusion of the neutral
      and charged (A and B) species of the drug. The observed fast and slow time
      constants for diffusion in the pH range 3-5 are attributed to the neutral (A) and
      ionic form (B) of Cp(6), respectively. At pH 6, the intensity of the generated SH
      signals on the addition of liposome reduced, and at physiological pH, it was too
      weak to be detected. These results are consistent with previous studies that show
      that the interaction between Cp(6) and egg-PC liposomes is pH dependent. At lower
      pH due to the presence of the hydrophobic species (A and B) of Cp(6), its
      interaction with liposomes is strong, and at higher pH, the abundance of the
      negatively charged hydrophilic species (C and D) decreases the interaction with
      the like charged liposomes. We have also studied the effect of increasing the
      bilayer rigidity by decreasing the temperature of the medium or by incorporating
      50 mol % cholesterol in the lipid bilayer and observed that lowering of
      temperature has more profound effect on the diffusion rates. The characteristics
      of the SH signal changed significantly when liposomes incorporating 50 mol %
      cholesterol were used at a low (3  degrees C) temperature. Under these
      conditions, the SH signal consisted of an instantaneous (<1s) followed by a
      slower rise (10-90s), and then, it decayed on a much longer time scale. This slow
      rise of the SH signal at pH 3 and 4 may be attributed to the temperature
      dependent adsorption of the anionic species (B) of Cp(6) with the liposomes.
      Further investigations are required in order to understand clearly the pH
      dependent diffusion of this drug across lipid bilayers.

PMID- 22414065
TI  - Polymorphisms in Toll-like receptor genes influence antibody responses to
      cytomegalovirus glycoprotein B vaccine.
AB  - BACKGROUND: Congenital Cytomegalovirus (CMV) infection is an important medical
      problem that has yet no current solution. A clinical trial of CMV glycoprotein B
      (gB) vaccine in young women showed promising efficacy. Improved understanding of
      the basis for prevention of CMV infection is essential for developing improved
      vaccines. RESULTS: We genotyped 142 women previously vaccinated with three doses
      of CMV gB for single nucleotide polymorphisms (SNPs) in TLR 1-4, 6, 7, 9, and 10,
      and their associated intracellular signaling genes. SNPs in the platelet-derived
      growth factor receptor (PDGFRA) and integrins were also selected based on their
      role in binding gB. Specific SNPs in TLR7 and IKBKE (inhibitor of nuclear factor
      kappa-B kinase subunit epsilon) were associated with antibody responses to gB
      vaccine. Homozygous carriers of the minor allele at four SNPs in TLR7 showed
      higher vaccination-induced antibody responses to gB compared to heterozygotes or
      homozygotes for the common allele. SNP rs1953090 in IKBKE was associated with
      changes in antibody level from second to third dose of vaccine; homozygotes for
      the minor allele exhibited lower antibody responses while homozygotes for the
      major allele showed increased responses over time. CONCLUSIONS: These data
      contribute to our understanding of the immunogenetic mechanisms underlying
      variations in the immune response to CMV vaccine.

PMID- 22414066
TI  - Relentless increase of resistance to fluoroquinolones and expanded-spectrum
      cephalosporins in Escherichia coli: 20 years of surveillance in resource-limited
      settings from Latin America.
AB  - Previous studies on commensal Escherichia coli from healthy children in the
      Bolivian Chaco have shown remarkable resistance rates to the old antibiotics
      since the early 1990s, and the emergence of resistance to newer drugs
      (fluoroquinolones and expanded-spectrum cephalosporins) in the 2000s. Here we
      report the results of a new survey conducted in 2011 in the same setting. Rectal
      swabs were obtained from 482 healthy children (aged 6-72 months) from three urban
      areas of the Bolivian Chaco. Screening for antibiotic-resistant E. coli was
      performed by a direct plating method, as in the previous studies. The blaCTX-M
      genes were investigated by PCR/sequencing, and CTX-M-producing isolates were
      subjected to genotyping and detection of several plasmid-mediated quinolone
      resistance mechanisms. Results showed high rates of resistance to nalidixic acid
      (76%), ciprofloxacin (44%) and expanded-spectrum cephalosporins (12.4%),
      demonstrating a relentless increase of resistance to those drugs over the past
      two decades. CTX-M-type extended-spectrum beta-lactamases were found to be
      widespread (12%, 97% of extended-spectrum beta-lactamase producers). Compared
      with the previous studies, CTX-M-producing E. coli underwent a dramatic
      dissemination (120-fold increase since early 2000s) and a radical change of
      dominant CTX-M groups (CTX-M-1 and CTX-M-9 groups versus CTX-M-2 group). Most CTX
      M producers were not susceptible to quinolones (91%), and 55% carried plasmid
      mediated quinolone resistance genes (different combinations of aac(6')-Ib-cr,
      qnrB and qepA). This study shows the rapid and remarkable increasing trend for
      resistance to fluoroquinolones and expanded-spectrum cephalosporins in one of the
      poorest regions of Latin America, and underscores the need for urgent control
      strategies aimed at preserving the efficacy of those drugs in similar settings.

PMID- 22414067
TI  - Non-convulsive status epilepticus of frontal origin in mucopolysaccharidosis type
      II successfully treated with ethosuximide.
AB  - At 7 years of age, a female with mucopolysaccharidosis type II (MPS II) showed a
      sudden deterioration in neurological function, a sleep disorder, and progressive
      behavioural impairment. Electroencephalography was performed 1 year and 8 months
      after the onset of the neurological regression and revealed continuous ictal
      activity in the frontal regions. The female was diagnosed as having frontal non
      convulsive status epilepticus. After 5 weeks of therapy with ethosuximide, the
      ictal electroencephalographic activity disappeared. At the same time, her sleep
      and cognitive and behavioural functions were observed to improve. This is the
      first case of MPS type II reported in an individual with non-convulsive status
      epilepticus. Two main forms of MPS II can be recognized: attenuated and severe.
      Severe MPS II is characterized by neurodegeneration. No study has explored the
      relationship between epilepsy and neurological deterioration in MPS II. Our
      observation shows that epilepsy may be a treatable cause of neurological
      regression in individuals with MPS II.

PMID- 22414069
TI  - Immunomodulation in helminth infections. Editorial.

PMID- 22414071
TI  - Fast separation and quantification method for nitroguanidine and 2,4
      dinitroanisole by ultrafast liquid chromatography-tandem mass spectrometry.
AB  - Explosives are now persistent environmental pollutants that are targets of
      remediation and monitoring in a wide array of environmental media. Nitroguanidine
      (NG) and 2,4-dinitroanisole (DNAN) are two insensitive energetic compounds
      recently used as munitions explosives. To protect our environment and human
      health, the levels of these compounds in soils and waters need to be monitored.
      However, no sensitive analytical methods, such as liquid chromatography-tandem
      mass spectrometry (LC-MS/MS), have been developed for detecting these new
      compounds at trace levels and to be concurrently applied to monitor the common
      explosives. In general, the concentrations of explosives in either soil or water
      samples are very low and widely distributed. Therefore, a fast and sensitive
      method is required to monitor those compounds and increase our ability to find
      and address the threats they pose to human health and ecological receptors. In
      this study, a fast and sensitive analytical method has been developed to
      quantitatively determine NG and DNAN in soil, tap water, and river water by using
      ultrafast LC-MS/MS. To make this method a comprehensive analytical technique for
      other explosives as well, it has included other commonly used explosives in the
      method development, such as octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine
      (HMX), 1,3,5-trinitroper-hydro-1,3,5-triazine (RDX), 2,4,6-trinitrotoluene (TNT),
      2-amino-4,6-dinitrotoluene (ADNT), and pentaerythritol tetranitrate (PETN). The
      method detection limits (MDLs) of these compounds in soil ranged from 0.2 to 5
      ppb, and a good linearity was obtained over a concentration range of 0.5-200 ppb.
      The recoveries of some compounds are equal to or better than the current EPA
      methods but with much higher sensitivities.

PMID- 22414068
TI  - Peptide chain dynamics in light and heavy water: zooming in on internal friction.
AB  - Frictional effects due to the chain itself, rather than the solvent, may have a
      significant effect on protein dynamics. Experimentally, such "internal friction"
      has been investigated by studying folding or binding kinetics at varying solvent
      viscosity; however, the molecular origin of these effects is hard to pinpoint. We
      consider the kinetics of disordered glycine-serine and alpha-helix forming
      alanine peptides and a coarse-grained protein folding model in explicit-solvent
      molecular dynamics simulations. By varying the solvent mass over more than two
      orders of magnitude, we alter only the solvent viscosity and not the folding free
      energy. Folding dynamics at the near-vanishing solvent viscosities accessible by
      this approach suggests that solvent and internal friction effects are
      intrinsically entangled. This finding is rationalized by calculation of the
      polymer end-to-end distance dynamics from a Rouse model that includes internal
      friction. An analysis of the friction profile along different reaction
      coordinates, extracted from the simulation data, demonstrates that internal as
      well as solvent friction varies substantially along the folding pathways and
      furthermore suggests a connection between friction and the formation of hydrogen
      bonds upon folding.

PMID- 22414072
TI  - Calorimetric study of glass transition in molecular liquids consisting of
      globular associates: dicyclorohexylmethanol and tricyclohexylmethanol.
AB  - Heat capacities of liquids and liquid-quenched glasses (LQGs) of
      dicyclorohexylmethanol (DCHM) and tricyclohexylmethanol (TCHM) were measured by
      adiabatic calorimetry. Upon cooling the liquid compounds, they undergo glass
      transitions around 250 and 265 K, respectively. Temperature dependence of the FT
      IR spectrum of TCHM liquid showed the gradual formation of dimers in the
      supercooled state with decreasing temperature. The magnitude of heat capacity
      jump at glass transition is discussed through a comparison with other low
      molecular mass LQG. Combining the present results with previous heat capacity
      results on crystalline TCHM, residual entropies of LQG and standard thermodynamic
      quantities are established for both compounds.

PMID- 22414073
TI  - Microbial reductive transformation of phyllosilicate Fe(III) and U(VI) in fluvial
      subsurface sediments.
AB  - The microbial reduction of Fe(III) and U(VI) was investigated in shallow aquifer
      sediments collected from subsurface flood deposits near the Hanford Reach of the
      Columbia River in Washington State. Increases in 0.5 N HCl-extractable Fe(II)
      were observed in incubated sediments and (57)Fe Mossbauer spectroscopy revealed
      that Fe(III) associated with phyllosilicates and pyroxene was reduced to Fe(II).
      Aqueous uranium(VI) concentrations decreased in subsurface sediments incubated in
      sulfate-containing synthetic groundwater with the rate and extent being greater
      in sediment amended with organic carbon. X-ray absorption spectroscopy of
      bioreduced sediments indicated that 67-77% of the U signal was U(VI), probably as
      an adsorbed species associated with a new or modified reactive mineral phase.
      Phylotypes within the Deltaproteobacteria were more common in Hanford sediments
      incubated with U(VI) than without, and in U(VI)-free incubations, members of the
      Clostridiales were dominant with sulfate-reducing phylotypes more common in the
      sulfate-amended sediments. These results demonstrate the potential for anaerobic
      reduction of phyllosilicate Fe(III) and sulfate in Hanford unconfined aquifer
      sediments and biotransformations involving reduction and adsorption leading to
      decreased aqueous U concentrations.

PMID- 22414074
TI  - Clinical service desires of medical cannabis patients.
AB  - BACKGROUND: Medical cannabis dispensaries following the social or hybrid model
      offer supplementary holistic services in addition to dispensing medical cannabis.
      Historically, alternative physical health services have been the norm for these
      dispensaries, including services such as yoga, acupuncture, or chiropractor
      visits. A clinical service dearth remains for medical cannabis patients seeking
      substance use, misuse, dependence, and mental health services. This study
      examined patient desires for various clinical services and level of willingness
      to participate in specific clinical services. METHODS: Anonymous survey data (N =
      303) were collected at Harborside Health Center (HHC), a medical cannabis
      dispensary in Oakland, CA. The sample was 70% male, 48% Caucasian and 21% African
      American. The mean male age was 38 years old and female mean age was 30. Sixty
      two percent of the male participants and 44% of the female participants are
      single. Sixteen percent of the population reported having a domestic partner.
      Forty six percent of the participants are employed full time, 41% have completed
      at least some college, and 49% make less than $40,000 a year. RESULTS: A
      significant portion of the sample, 62%, indicated a desire to participate in free
      clinical services at HHC, 34% would like more information about substances and
      use, and 41% want to learn more about reducing harms from substance use. About
      one quarter of the participants marked "would" or "likely would" participate in
      individual services such as consultation. Approximately 20% indicated "would" or
      "likely would" participate in psycho-educational forums, harm reduction
      information sharing sessions, online support groups, and coping, life, and social
      skills group. There was little interest in traditional NA/AA 12-step groups or
      adapted 12-step groups. CONCLUSIONS: Desired clinical services can be qualified
      as a combination of harm reduction, educational, skills-based, peer support and
      therapeutic individual and group services. Results suggest that medical cannabis
      patients seek more information about various substances, including cannabis.
      Dispensaries can help to decrease gaps in substance education and clinical
      services and fulfill unmet clinical desires. More research is necessary in
      additional medical cannabis dispensaries in different geographic settings with
      different service delivery models.

PMID- 22414075
TI  - A novel rapid prototyping and finite element method-based development of the
      patient-specific temporomandibular joint implant.
AB  - OBJECTIVE: The objective of this study was to fabricate a successful implant for
      temporomandibular joint (TMJ) disorder patients who could not be treated through
      conventional surgeries. METHODS: A custom-made implant was fabricated using rapid
      prototyping (RP) for the TMJ surgery. The stability of the metallic implant was
      validated using a finite element analysis. RESULTS: The results of finite
      elements were stable and the design of the TMJ implant was suitable as per the
      patient's need. The customised implant was made using a fused deposition
      modelling method of RP and a vertical machining centre. The implant has provided
      normal jaw function for over 2 years since surgery. CONCLUSIONS: The approach
      utilised will be helpful in providing successful treatment to the deformed
      mandible and the mandible joints. This method allows to customise and to
      accurately fabricatie the implant. Advantages of this approach are that the
      physical model of the implant was tested for stability before the implantation,
      the surgeon can plan and rehearse the surgery in advance, it is a less invasive
      and less time-consuming surgical procedure.

PMID- 22414076
TI  - Time-frequency analysis of phonocardiogram signals using wavelet transform: a
      comparative study.
AB  - Analysis of phonocardiogram (PCG) signals provides a non-invasive means to
      determine the abnormalities caused by cardiovascular system pathology. In
      general, time-frequency representation (TFR) methods are used to study the PCG
      signal because it is one of the non-stationary bio-signals. The continuous
      wavelet transform (CWT) is especially suitable for the analysis of non-stationary
      signals and to obtain the TFR, due to its high resolution, both in time and in
      frequency and has recently become a favourite tool. It decomposes a signal in
      terms of elementary contributions called wavelets, which are shifted and dilated
      copies of a fixed mother wavelet function, and yields a joint TFR. Although the
      basic characteristics of the wavelets are similar, each type of the wavelets
      produces a different TFR. In this study, eight real types of the most known
      wavelets are examined on typical PCG signals indicating heart abnormalities in
      order to determine the best wavelet to obtain a reliable TFR. For this purpose,
      the wavelet energy and frequency spectrum estimations based on the CWT and the
      spectra of the chosen wavelets were compared with the energy distribution and the
      autoregressive frequency spectra in order to determine the most suitable wavelet.
      The results show that Morlet wavelet is the most reliable wavelet for the time
      frequency analysis of PCG signals.

PMID- 22414077
TI  - A study of direct moxibustion using mathematical methods.
AB  - Direct moxibustion is an important and widely used treatment method in
      traditional medical science. The use of a mathematical method to analyse direct
      moxibustion treatment is necessary and helpful in exploring the new direct
      moxibustion instruments and their standardisation. Thus, this paper aims to use a
      mathematical method to study direct moxibustion in skin to demonstrate a direct
      relationship between direct moxibustion and skin stimuli. In this paper, the
      transient thermal response of skin layers is analysed to study direct moxibustion
      using the data got from standardised method to measure the temperature of a
      burning moxa cone. Numerical simulations based on an appropriate finite element
      model are developed to predict the heat transfer, thermal damage and thermal
      stress distribution of barley moxa cones and jujube moxa cones in the skin
      tissue. The results are verified by the ancient literatures of traditional
      Chinese medicine and clinical application, and showed that mathematical method
      can be a good interface between moxa cone and skin tissue providing the numerical
      value basis for moxibustion.

PMID- 22414078
TI  - Selective serotonin reuptake inhibitors (SSRIs): therapeutic drug monitoring and
      pharmacological interactions.
AB  - New-generation antidepressants are a heterogeneous class of drugs used in the
      treatment of depression and related disorders. This review deals with the first
      new-generation antidepressant class to enter the pharmaceutical market, i.e.,
      selective serotonin reuptake inhibitors (SSRIs), which are still the most
      prescribed and widely used ones. Their common characteristics are the comparable
      clinical efficacy, good tolerability and relative safety in comparison to "first
      generation antidepressants", i.e. classic tricyclic antidepressants and monoamine
      oxidase inhibitors. This class of drugs includes fluoxetine, citalopram,
      paroxetine, sertraline, fluvoxamine and, since 2011, vilazodone. In this review,
      the main pharmacodynamic and pharmacokinetic properties of the six commercially
      available SSRIs are described, focusing on side and toxic effects, chemical
      clinical correlations, interactions with other drugs, the role of therapeutic
      drug monitoring (TDM) and related bioanalytical methodologies.

PMID- 22414079
TI  - UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) inhibitors:
      a new class of antibacterial agents.
AB  - The rapid increase of health-threatening infections by Gram-negative pathogens
      along with the emergence of multidrug-resistant bacterial strains demands the
      development of novel antibiotics directed against the previously unexploited
      targets. One of the promising targets in Gram-negative bacteria is the zinc
      dependent metalloamidase, UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine
      deacetylase (LpxC). LpxC catalyzes the first committed, second overall step in
      the biosynthetic pathway of lipid A. Thus, research on LpxC inhibitors as
      antibacterial agents has become an attractive field in the development of the
      novel antibiotic therapy of Gram-negative bacteria. In this review, we will
      summarize the recent progress in the studies on the structure, catalytic
      mechanism and regulation of LpxC and the current development of LpxC inhibitors.

PMID- 22414080
TI  - How is gene transfection able to improve current chemotherapy? The role of
      combined therapy in cancer treatment.
AB  - Despite advances in cancer treatment, a large number of patients eventually
      develop metastatic disease that is generally incurable. Systemic chemotherapy
      remains the standard treatment for these patients. Several chemotherapeutic
      combinations have proven effective in the management of cancer. Paradoxically,
      although the purpose of polychemotherapy is to improve the prognosis and prolong
      the survival of patients, it often carries considerable toxicity that causes
      substantial adverse symptoms. For this reason, a major goal of cancer research is
      to improve the effectiveness of these cytotoxic agents and reduce their adverse
      effects. Gene transfer has been proposed as a new strategy to enhance the
      efficacy of anti-tumor drugs in the treatment of intractable or metastatic
      cancers. In fact, the association of gene therapy and drugs (combined therapy)
      has been reported to increase the anti-proliferative effect of classical
      treatments in lung, bladder, pancreatic, colorectal and breast cancers, among
      others. Various especially promising therapies have been proposed in this
      context, including the use of suicide genes, antisense oligonucleotides,
      ribozymes and RNA interference. In this chapter, we review recent progress in the
      development of novel anti-cancer strategies that associate cytotoxic agents with
      gene transfer to enhance their antitumor effect.

PMID- 22414081
TI  - Novel patented SRC kinase inhibitor.
AB  - Src family of protein tyrosine kinases (SFKs) plays key roles in the regulation
      of signal transductions in cellular processes. However, hyper-activated SFKs lead
      to uncontrolled cell proliferation and cancers. Src-targeted compounds were
      developed to block the cell proliferation signal transductions for cancer
      therapy. Src kinase domain inhibitors were designed, synthesized and evaluated as
      anticancer agents, while the patents applied at the same time. Great progress has
      been made in the Src kinase inhibitor area. Herein, some predominant patents
      about Src kinase inhibitors of the recent years are reviewed.

PMID- 22414082
TI  - Modulation of inflammatory immune reactions by low-dose ionizing radiation:
      molecular mechanisms and clinical application.
AB  - During the last decade, a multitude of experimental evidence has accumulated
      showing that low-dose radiation therapy (single dose 0.5-1 Gy) functionally
      modulates a variety of inflammatory processes and cellular compounds including
      endothelial (EC), mononuclear (PBMC) and polymorphonuclear (PMN) cells,
      respectively. These modulations comprise a hampered leukocyte adhesion to EC,
      induction of apoptosis, a reduced activity of the inducible nitric oxide
      synthase, and a lowered oxidative burst in macrophages. Moreover, irradiation
      with a single dose between 0.5-0.7 Gy has been shown to induce the expression of
      X-chromosome linked inhibitor of apoptosis and transforming growth factor beta 1,
      to reduce the expression of E-selectin and L-selectin from EC and PBMC, and to
      hamper secretion of Interleukin-1, or chemokine CCL20 from macrophages and PMN.
      Notably, a common feature of most of these responses is that they display
      discontinuous or biphasic dose dependencies, shared with "non-targeted" effects
      of low-dose irradiation exposure like the bystander response and hyper
      radiosensitivity. Thus, the purpose of the present review is to discuss recent
      developments in the understanding of low-dose irradiation immune modulating
      properties with special emphasis on discontinuous dose response relationships.

PMID- 22414083
TI  - Induction of abscopal anti-tumor immunity and immunogenic tumor cell death by
      ionizing irradiation - implications for cancer therapies.
AB  - Although cancer progression is primarily driven by the expansion of tumor cells,
      the tumor microenvironment and anti-tumor immunity also play important roles.
      Herein, we consider how tumors can become established by escaping immune
      surveillance and also how cancer cells can be rendered visible to the immune
      system by standard therapies such as radiotherapy or chemotherapy, either alone
      or in combination with additional immune stimulators. Although local radiotherapy
      results in DNA damage (targeted effects), it is also capable of inducing
      immunogenic forms of tumor cell death which are associated with a release of
      immune activating danger signals (non-targeted effects), such as necrosis.
      Necrotic tumor cells may result from continued exposure to death stimuli and/or
      an impaired phosphatidylserine (PS) dependent clearance of the dying tumor cells.
      In such circumstances, mature dendritic cells take up tumor antigen and mediate
      the induction of adaptive and innate anti-tumor immunity. Locally-triggered,
      systemic immune activation can also lead to a spontaneous regression of tumors or
      metastases that are outside the radiation field - an effect which is termed
      abscopal. Preclinical studies have demonstrated that combining radiotherapy with
      immune stimulation can induce anti-tumor immunity. Given that it takes time for
      immunity to develop following exposure to immunogenic tumor cells, we propose
      practical combination therapies that should be considered as a basis for future
      research and clinical practice. It is essential that radiation oncologists become
      more aware of the importance of the immune system to the success of cancer
      therapy.

PMID- 22414084
TI  - The effect of chemotherapy/radiotherapy on cancerous pattern recognition by NK
      cells.
AB  - In recent years, the effects of cancer chemotherapy and radiotherapy (CT/RT)
      regimens as they apply to the immune system have been explored. NK cells
      represent the main cytotoxic arm of the innate immune system, and their
      functionality is vital to establishing an effective anti tumor immune response.
      This review examines current CT/RT interventions in light of their effects on NK
      cell functionality. The effects of CT/RT on the expression of the various ligands
      for activating and inhibitory NK cell receptors are discussed. Expression of
      ligands for the activating NKG2D receptor is enhanced by cell stress; accordingly
      there are numerous reports of their higher expression in cells exposed to various
      CT/RT agents. In contrast, some agents have been reported to cause ligand
      shedding, which can serve to inhibit NK cell activity. Reported effects of CT/RT
      on tumor expression of ligands for the activating Natural Cytotoxicity Receptors,
      and of HLA class I ligands for NK cell inhibitory receptors are also noted.
      Additionally, we describe reports concerning the direct effects of CT/RT on NK
      cell function. Many treatments adversely affect NK cell function directly, but
      observations made through in vitro systems may differ from those obtained
      utilizing clinical samples. The effects of CT/RT on both direct NK cell
      cytotoxicity and on NK cell-mediated Antibody Dependent Cellular Cytotoxicity are
      explored. Taken together, CT/RT affects NK cell anti-tumor immunity from multiple
      angles. The interplay is complex, and future work is needed to achieve the
      optimal synergy between CT/RT and innate as well as adaptive immunity in the
      treatment of cancer.

PMID- 22414085
TI  - Radiation-induced stress proteins - the role of heat shock proteins (HSP) in anti
      tumor responses.
AB  - Together with surgery and chemotherapy, ionizing irradiation is one of the key
      therapeutic approaches to treat cancer. More than 50 percent of all cancer
      patients will receive radiotherapeutic intervention at some stage of their
      disease. The more precise instrumentation for delivery of radiotherapy and the
      emphasis on hypofractionation technologies have drastically improved loco
      regional tumor control within the last decades. However, the appearance of
      distant metastases often requires additional systemic treatment modalities such
      as chemotherapy. High dose chemotherapy is generally considered as
      immunosuppressive and can cause severe adverse effects. Therefore, we want to
      elucidate the effects of ionizing irradiation on the immune system and provide
      immunological treatment strategies which are induced by the host's stress
      response. Similar to other stressors, ionizing irradiation is known to enhance
      the synthesis of a variety of immune-stimulatory and -modulating molecules such
      as heat shock proteins (HSP), high mobility group box 1 (HMGB1) and survivin.
      Herein, we focus on HSP that exhibit an unusual cell membrane localization and
      release mechanism in tumor cells. These tumor-specific characteristics render HSP
      as ideal targets for therapeutic interventions. Depending on their intra/membrane
      and extracellular localization HSP have the ability to protect tumor cells from
      stress-induced lethal damage by interfering with antiapoptotic pathways or to
      elicit anti-cancer immunity.

PMID- 22414086
TI  - The interaction of NK cells and dendritic cells in the tumor environment: how to
      enforce NK cell & DC action under immunosuppressive conditions?
AB  - The crosstalk of natural killer (NK) and dendritic cells (DCs) plays an important
      role in the induction of the tumor-specific immune response against cancer.
      During the last decade, our advanced understanding of the immune system led to
      the development of new therapeutic strategies in the field of immunotherapy and
      cellular immunology. However, these immunotherapeutic concepts have not been as
      successful as initially expected because of their inability to counteract cancer
      induced immunosuppressive pathways. Some of the major difficulties of effective
      cellular immunotherapy are the highly immunosuppressive factors induced by tumor
      cells themselves or by their microenvironment. Therefore, one major challenge in
      immunotherapy is the question: "How to enforce NK cell & DC action under
      immunosuppressive conditions?" This review focuses on the current knowledge on
      the tumor microenvironment, the crosstalk of NK cells and DCs, as well as their
      deregulation in the complex interplay with the immunosuppressive tumor
      microenvironment. We further discuss possible strategies to minimize the negative
      impact of the tumor microenvironment on the immune system.

PMID- 22414087
TI  - ChemoImmunoModulation: immune regulation by the antineoplastic chemotherapeutic
      agents.
AB  - Since 1948, when Farber et al. introduced aminopterin, the first chemotherapeutic
      agent, more than 100 such agents have come into use. Initially, antitumor
      chemotherapies were thought to produce only antiproliferative or cytotoxic
      effects on dividing tumor cells as it was often associated with the damage to
      healthy tissues and the development of resistant tumor clones. However, that view
      has been changing as a consequence of recent demonstrations that several
      antineoplastic drugs, even at low doses, have antiangiogenic and sometimes
      immunomodulating effects. In addition, new studies indicate that lowering the
      dose of conventional cytotoxic agents and combining chemotherapy with other
      modalities may not only decrease the toxicity of conventional chemotherapy, but
      also up-regulate the efficacy of different anticancer therapies. Giving
      chemotherapy in this manner has several potential advantages, including
      impediment of the onset of mutation-dependent mechanisms of acquired drug
      resistance and increase in the efficacy and durability of combinatorial
      therapeutic modalities. Certain "immunogenic" forms of cancer chemotherapy may
      cause indirect activation of immune cells due to the accessibility of tumor
      antigens and certain "danger" signals. Furthermore, new findings indicate that
      several chemotherapeutic agents can directly activate immune cells when used in
      ultra low noncytotoxic concentrations, the new phenomenon that was termed
      chemoimmunomodulation. The goal of this review is to analyze the immune
      modulating properties of antineoplastic chemotherapeutic agents and present new
      evidence of the immunostimulating potentials of several agents used in low and
      ultra low nontoxic doses. Therapeutic potentials of combined chemo
      immunotherapeutic regimens have been extensively reviewed in a variety of recent
      publications and will not be discussed.

PMID- 22414088
TI  - In vitro - in vivo correlation of gene expression alterations induced by liver
      carcinogens.
AB  - Although cultivated hepatocytes are widely used in the studies of drug
      metabolism, their application in toxicogenomics is considered as problematic,
      because previous studies have reported only little overlap between chemically
      induced gene expression alterations in liver in vivo and in cultivated
      hepatocytes. Here, we identified 22 genes that were altered in livers of rats
      after oral administration of the liver carcinogens aflatoxin B1 (AB1), 2
      nitrofluorene (2-NF), methapyrilene (MP) or piperonyl-butoxide (PBO). The
      functions of the 22 genes have been classified into two groups. Genes related to
      stress response, DNA repair or metabolism and genes associated with cell
      proliferation, respectively. Next, rat hepatocyte sandwich cultures were exposed
      to AB1, 2-NF, MP or PBO for 24h and expression of the above mentioned genes was
      determined by RT-qPCR. Significant correlations between the degree of gene
      expression alterations in vivo and in vitro were obtained for the stress, DNA
      repair and metabolism associated genes at concentrations covering a range from
      cytotoxic concentrations to non-toxic/in vivo relevant concentrations. In
      contrast to the stress associated genes, no significant in vivo/in vitro
      correlation was obtained for the genes associated with cell proliferation. To
      understand the reason of this discrepancy, we compared replacement proliferation
      in vivo and in vitro. While hepatocytes in vivo, killed after administration of
      hepatotoxic compounds, are rapidly replaced by proliferating surviving cells, in
      vitro no replacement proliferation as evidenced by BrdU incorporation was
      observed after washing out hepatotoxic concentrations of MP. In conclusion, there
      is a good correlation between gene expression alterations induced by liver
      carcinogens in vivo and in cultivated hepatocytes. However, it should be
      considered that cultivated primary hepatocytes do not show replacement
      proliferation explaining the in vivo/in vitro discrepancy concerning
      proliferation associated genes.

PMID- 22414089
TI  - Chemical metabolism of medicinal compounds from natural botanicals.
AB  - Traditional Chinese medicine (TCM) and its natural products are complex mixtures
      containing hundreds of chemically different constituents but only a few
      components are responsible for the pharmacological effects and bioactivities. In
      order to clarify the functional mechanism of active compounds, the studies on
      metabolism are of great significance and necessity. Previously, research mainly
      focused on the aspect of pharmacokinetics, however in recent years, chemical
      metabolism of active compounds has drawn increasing attention. Researches on the
      chemical metabolism of single phytochemicals help to understand the
      transformation process in vivo and mechanism of action, also contribute to
      pharmacodynamics and toxicology studies and new drug development. In the present
      paper, the chemical metabolism of nine categories of phytochemicals was reviewed.
      This review focused on pharmacological action, metabolic characteristics,
      metabolic pathways, metabolites and assay method of alkaloids, flavonoids,
      saponins, terpenoids, stilbenes, phenols, quinones, lignans and esters. The
      parent drugs, perhaps the metabolites, or they together play a role in
      pharmacological effects. And different routes of administration may lead to
      different results of transformation pathways and metabolites. Moreover, high-tech
      assay methods, particularly the combined use of modern instrument analytical
      techniques, are beneficial to the research of drug metabolism.

PMID- 22414090
TI  - Bcl-2 inhibitors: emerging drugs in cancer therapy.
AB  - Dose-limiting toxicity to healthy tissues is among the major hurdles in
      anticancer treatment along with intrinsic or acquired multi-drug resistance.
      Development of small molecule inhibitors (SMI) specific for antiapoptotic Bcl-2
      proteins is a novel approach in a way that these antagonists are aimed to
      interfere with specific protein-protein interactions unlike conventional chemo
      /radiotherapies. SMIs of antiapoptotic Bcl-2 proteins are assumed to compete with
      proapoptotic Bcl-2s to occupy BH3 docking grooves on the surfaces of
      antiapoptotic family members. Instead of directly initiating cell death, these
      inhibitors are intended to decrease apoptotic threshold in tumor cells that were
      already primed to death. In this regard, antiapoptotic Bcl-2 protein SMIs have
      the advantage of lower normal tissue toxicity relative to conventional anticancer
      therapies that interfere with general mechanisms including DNA synthesis, mitosis
      and tyrosine kinase activity. Besides, Bcl-2 antagonists were shown to potentiate
      efficacies of established drugs in several hematological malignancies and solid
      tumors which render them promising candidates for combination anticancer therapy.
      Utilizing these SMIs in such a way may prove to decrease the patient drug load by
      diminishing the required chemo-/radiotherapy dose. This review summarizes and
      compares BH3 mimetics on the basis of specificity, mode of action and efficacy,
      as well as providing remarks on their therapeutical potential and routes of
      development in near future.

PMID- 22414091
TI  - Prevalence of bacteriocin activities and bacteriocin-encoding genes in
      enterococcal clinical isolates in Iran.
AB  - The aim of the project was to isolate and characterize bacteriocin-producing
      enterococci, as well as determine the prevalence of enterocin structural genes in
      187 enterococcal clinical isolates from the northwest of Iran. The isolates were
      screened for antibacterial activity against 15 different indicator strains. The
      proteinaceous nature of the antimicrobial substances was confirmed by sensitivity
      to proteinase K; their stability to heat treatment was tested at 60  degrees C
      and 100  degrees C for 20 and 10 min, respectively. The PCR method was applied to
      detect previously identified enterocin genes. Our results showed that 38 (20.3%)
      of the enterococcal isolates were considered to be potential bacteriocinogenic
      strains. Furthermore, genes encoding diverse bacteriocin are highly distributed
      among clinical enterococci, and the strains with multi-bacteriocin genes
      displayed high antimicrobial activity. Enterocin A, enterolysin A, and enterocin
      L50A/B were the most abundant structural genes detected in bacteriocinogenic
      strains. This work is the first survey on the prevalence of bacteriocin genes
      among clinical enterococci in Iran that has isolated a strain with high
      antimicrobial activity and sensitivity to clinically relevant antibiotics.

PMID- 22414092
TI  - Diagnostic value of diffusion-weighted magnetic resonance imaging compared with
      fluorodeoxyglucose positron emission tomography/computed tomography for
      pancreatic malignancy: a meta-analysis using a hierarchical regression model.
AB  - BACKGROUND AND AIM: To obtain diagnostic performance of diffusion-weighted
      magnetic resonance imaging (DWI) and fluorine 18 fluorodeoxyglucose (FDG)
      positron emission tomography/computed tomography (PET/CT) in the detection of
      pancreatic malignancy. METHODS: We performed a meta-analysis of all available
      studies of the diagnostic performance of DWI and PET/CT for pancreatic
      malignancy. MEDLINE, EMBASE, Cochrane library and some other databases were
      searched for initial studies. We determined sensitivities and specificities
      across studies, calculated positive and negative likelihood ratios (LR+ and LR-),
      and constructed summary receiver operating characteristic curves (SROC) using
      hierarchical regression models. RESULTS: Across 16 studies with 804 patients,
      PET/CT sensitivity was 0.87 (95% confidence interval [CI], 0.82, 0.81) and
      specificity was 0.83 (95% CI, 0.71, 0.91). Overall, LR+ was 5.84 (95% CI, 4.59,
      7.42) and LR- was 0.24 (95% CI, 0.17, 0.33). DWI sensitivity was 0.85 (95% CI,
      0.74, 0.92) and specificity was 0.91 (95% CI, 0.71, 0.98). LR+ was 9.53 (95% CI,
      2.41, 37.65) and LR- was 0.17 (95% CI, 0.09, 0.32). In subgroup analysis, the
      sensitivity of enhanced versus unenhanced PET/CT in the detection of pancreatic
      cancer was 0.91 (95% CI, 0.86, 0.96) versus 0.84 (95% CI, 0.78, 0.90) (P > 0.05),
      the specificity 0.88 (95% CI, 0.73, 1.00) versus 0.81 (95% CI, 0.69, 0.94) (P >
      0.05). CONCLUSION: Positron emission tomography/computed tomography (PET/CT) was
      highly sensitive and DWI was a highly specific modality in diagnosing patients
      with pancreatic malignancy. PET/CT and DWI could play different roles in
      diagnosing pancreatic carcinoma. Enhanced PET/CT seems to be superior to
      unenhanced PET/CT. Further larger prospective studies are needed to establish its
      value for diagnosis in pancreatic cancer.

PMID- 22414094
TI  - Role of blunt suture needle in episiotomy repair at uncomplicated vaginal
      deliveries in reducing glove perforation rate: a randomized controlled trial.
AB  - AIM: The aim of this study was to evaluate the role of blunt suture needles for
      episiotomy repair at uncomplicated vaginal deliveries in reducing glove
      perforation rate. METHODS: This was a prospective randomized controlled trial
      wherein 300 nulliparous women with uncomplicated vaginal deliveries were
      randomized to episiotomy repair with either blunt or sharp suture needles.
      Patient demographics and clinical variables were collected. Postoperatively, the
      surgeons were surveyed regarding ease of using the needle, and glove perforation
      was determined by three tests: air insufflation, water filling and water load.
      RESULTS: A total of 41 perforations occurred in the 39 episiotomy repairs with
      glove perforations (13%). There was a significantly higher number of glove
      perforations using the sharp suture needles (28/150; 18.7%) than with the blunt
      suture needles (11/150; 7.3%) (P = 0.005). Glove perforation of the non-dominant
      hand occurred in 90% of the cases. Using a blunt suture needle took significantly
      more time (P < 0.001) to complete the repair than using a sharp needle. Surgeons
      reported that blunt needles were more difficult to use than sharp needles (P <
      0.001). CONCLUSION: Blunt suture needles for episiotomy repair were shown to have
      a significantly lower instance of glove perforation but required more time and
      are perceived to be more difficult to complete the repair as compared to sharp
      needles.

PMID- 22414093
TI  - European data on stem cell mobilization with plerixafor in patients with
      nonhematologic diseases: an analysis of the European consortium of stem cell
      mobilization.
AB  - BACKGROUND: Plerixafor with granulocyte-colony-stimulating factor (G-CSF) has
      been shown to enhance stem cell mobilization in patients with multiple myeloma
      and lymphoma with previous mobilization failure. In this European named patient
      program we report the experience in insufficiently mobilizing patients diagnosed
      with nonhematologic diseases. STUDY DESIGN AND METHODS: Thirty-three patients
      with germ cell tumor (n=11), Ewing sarcoma (n=6), Wiscott-Aldrich disease (n=5),
      neuroblastoma (n=4), and other nonhematologic diseases (n=7) were included in the
      study. Plerixafor was limited to patients with previous or current stem cell
      mobilization failure and given after 4 days of G-CSF (n=21) or after chemotherapy
      and G-CSF (n=12) in patients who mobilized poorly. RESULTS: Overall, 28 (85%)
      patients succeeded in collecting at least 2*10(6)/kg body weight (b.w.) CD34+
      cells (median, 5.0*10(6)/kg b.w. CD34+ cells; range, 2.0*10(6)-29.5*10(6)/kg b.w.
      CD34+ cells), and five (15%) patients collected a median of 1.5*10(6)/kg b.w.
      CD34+ cells (range, 0.9*10(6)-1.8*10(6)/kg b.w. CD34+ cells). Nineteen patients
      proceeded to transplantation. The median dose of CD34+ cells infused was
      3.3*10(6)/kg b.w. (range, 2.3*10(6)-6.7*10(6)/kg b.w. CD34+ cells). The median
      numbers of days to neutrophil and platelet engraftment were 11 (range, 9-12) and
      15 (range, 10-25) days, respectively. CONCLUSION: These data emphasize the role
      of plerixafor in combination with G-CSF or chemotherapy and G-CSF as an effective
      mobilization regimen with the potential of successful stem cell collection.
      Accordingly, plerixafor seems to be safe and effective in patients with
      nonhematologic diseases. Larger prospective studies are warranted to further
      assess its use in these patients.

PMID- 22414095
TI  - Local tumor control after retreatment of spinal metastasis using stereotactic
      body radiotherapy; comparison with initial treatment group.
AB  - BACKGROUND: The aim of this study is to evaluate local control rates after
      stereotactic body radiotherapy (SBRT) in recurrent spinal metastasis after
      external beam radiotherapy (EBRT) and new spinal metastatic lesions. MATERIAL AND
      METHODS: Retrospective review of medical records and radiological data was
      performed on 54 retreatment and 131 initial SBRT patients. To compare various
      fractionation schedules, the biologically effective dose (BED) was applied. SBRT
      dose was calculated with linear-quadratic model and normalized to a 2-Gy
      equivalent dose (nBED, alpha/beta =2 Gy for spinal cord, alpha/beta =10 Gy for
      tumor). Doses to a point within the spinal cord that received the maximum dose
      (Pmax) were checked. Local control failure was defined as progression by imaging
      study. Overall survival, progression free survival, delivered radiation dose to
      tumor and spinal cord, and spinal cord Pmax nBED were compared in two groups.
      RESULTS: The mean delivered radiation doses to tumor margin during SBRT were 51.1
      Gy2/10 (retreatment) and 50.7 Gy2/10 (initial treatment). Mean survival was 29.6
      months (overall)/20.7 months (retreatment)/ 32.4 months (initial treatment). Mean
      progression free period was 23.9 months (overall)/18.0 months (retreatment)/ 26.0
      months (initial treatment). Radiological control rates of retreatment and initial
      treatment group were 96%/95% at six months, 81%/89% at 12 months and 79%/90% at
      24 months. Among 54 retreatment lesions, 13 lesions showed local control failure
      during follow-up. With regard to spinal cord radiation dose during SBRT, Spinal
      cord Pmax nBED was 46.2 Gy2/2 (retreatment) and 48.7 Gy2/2 (initial treatment).
      In retreatment group, total nBED to spinal cord was a mean of 83.4 Gy2/2. There
      was no case of radiation myelopathy detected. CONCLUSIONS: Retreatment of spinal
      metastases using SBRT provided effective local control without neurological
      complications.

PMID- 22414097
TI  - Plasmonic properties of gold nanoparticles separated from a gold mirror by an
      ultrathin oxide.
AB  - That a nanoparticle (NP) (for example of gold) residing above a gold mirror is
      almost as effective a surface enhanced Raman scattering (SERS) substrate (when
      illuminated with light of the correct polarization and wavelength) as two closely
      coupled gold nanoparticles has been known for some time. The NP-overmirror (NPOM)
      configuration has the valuable advantage that it is amenable to top-down
      fabrication. We have fabricated a series of Au-NPOM substrates with varying but
      thin atomic layer-deposited oxide spacer and measured the SERS enhancement as a
      function of spacer thickness and angle of incidence (AOI). These were compared
      with high-quality finite-difference time-domain calculations, which reproduce the
      observed spacer thickness and AOI dependences faithfully. The SERS intensity is
      expected to be strongly affected by the AOI on account for the fact that the hot
      spot formed in the space between the NP and the mirror is most efficiently
      excited with an electromagnetic field component that is normal to the surface of
      the mirror. Intriguingly we find that the SERS intensity maximizes at ~60 degrees
      and show that this is due to the coherent superposition of the incident and the
      reflected field components. The observed SERS intensity is also shown to be very
      sensitive to the dielectric constant of the oxide spacer layer with the most
      intense signals obtained when using a low dielectric constant oxide layer
      (SiO(2)).

PMID- 22414096
TI  - Do radiation oncologists tailor information to patients needs? And, if so, does
      it affect patients?
AB  - BACKGROUND: Our study aims to investigate whether information given by radiation
      oncologists to their patients is tailored to the patient's desired level of
      information and, if so, what the effect of tailoring is on patient-reported
      outcomes, i.e. satisfaction, health, anxiety and self-efficacy. MATERIAL AND
      METHODS: Consecutive radiotherapy patients (n = 150) completed a baseline
      questionnaire one week before their initial consultation, immediately following
      this consultation, and again one week prior to their first follow-up visit. The
      initial consultation was videotaped and 10 radiation oncologists' information
      giving behavior (content and duration) analyzed. RESULTS: The overall amount of
      information provided by the radiation oncologists matched with patients'
      information needs in 50.8% (k = 0.07) of the consultations. No significant
      associations between tailored information giving and patient-reported outcomes
      were found, except for tailoring of information on procedures, and patients'
      anxiety and global health. These associations were no longer significant when
      correcting for patients' background characteristics. CONCLUSION: This study shows
      that radiation oncologists poorly tailor their information to the needs of their
      patients. However, lack of tailoring is not associated with worse patient
      reported outcomes. Until more evidence is available, radiation oncologists may
      explicitly ask patients about their information preferences and tailor the
      information provided accordingly.

PMID- 22414098
TI  - Modulation of the immune system by ionizing irradiation and chemotherapeutic
      agents - contribution of immune activation and blocking of immune suppression to
      cancer therapy success.

PMID- 22414099
TI  - Editorial: Coming back to nature: plants as a vital source of pharmaceutically
      important metabolites.

PMID- 22414100
TI  - Power from the garden: plant compounds as inhibitors of the hallmarks of cancer.
AB  - On December 23rd, 1971, President Richard Nixon signed the National Cancer Act
      and invested more than $ 100 million "to launch an intensive campaign to find a
      cure for cancer". Today, despite these considerable efforts, cancer still remains
      a very aggressive silent killer all over the world. Moreover, over the last
      decade, novel synthetic chemotherapeutic agents currently in use in the clinics
      did not succeed in fulfilling their expectations even though they are very cost
      intensive. In parallel, there is increasing evidence for the potential of plant
      derived compounds on the inhibition of different steps of tumor genesis and
      associated inflammatory processes, underlining the importance of these products
      in cancer prevention and therapy. This review summarizes the impact of selected
      natural compounds on the eight major alterations, known as the cancer hallmarks,
      and also on their two enabling characteristics that were coined by Hanahan and
      Weinberg earlier. Altogether these ten alterations are responsible for the
      progressive transition of healthy cells into neoplastic ones and their further
      dissemination in the body. With this review, we try to highlight molecular
      mechanisms by which plant extracts and their purified active components fight and
      overcome these pathological variations of the cell signaling pathways for the
      improvement of prevention and therapy. We truly believe that all diseases can be
      found in Nature and that Nature also provides the efficient cures.

PMID- 22414101
TI  - Anti-inflammatory agents from plants: progress and potential.
AB  - The identification of substances that can promote the resolution of inflammation
      in a way that is homeostatic, modulatory, efficient, and well-tolerated by the
      body is of fundamental importance. Traditional medicines have long provided front
      line pharmacotherapy for many millions of people worldwide. Medicinal extracts
      are a rich source of therapeutic leads for the pharmaceutical industry. The use
      of medicinal plant therapies to treat chronic illness, including rheumatoid
      arthritis (RA) and inflammatory bowel disease (IBD), is thus widespread and on
      the rise.The aim of this review is to present recent progress in clinical anti
      inflammatory studies of plant extracts and compound leads such as green tea
      polyphenols, curcumin, resveratrol, boswellic acid, and cucurbitacins, among
      others, against chronic inflammatory diseases, mainly RA and IBD. In this
      context, the present paper also highlights the most promising experimental data
      on those plant extracts and pure compounds active in animal models of the
      aforementioned diseases.

PMID- 22414103
TI  - The potential of secondary metabolites from plants as drugs or leads against
      protozoan neglected diseases - part I.
AB  - Infections with protozoan parasites are a major cause of disease and mortality in
      many tropical countries of the world. Diseases caused by species of the genera
      Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania
      (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical
      Diseases" (NTDs) defined as such by WHO due to the neglect of financial
      investment into research and development of new drugs by a large part of
      pharmaceutical industry and neglect of public awareness in high income countries.
      Another major tropical protozoan disease is malaria (caused by various Plasmodium
      species), which -although not mentioned currently by the WHO as a neglected
      disease- still represents a major problem, especially to people living under poor
      circumstances in tropical countries. Malaria causes by far the highest number of
      deaths of all protozoan infections and is often (as in this review) included in
      the NTDs. The mentioned diseases threaten many millions of lives world-wide and
      they are mostly associated with poor socioeconomic and hygienic environment.
      Existing therapies suffer from various shortcomings, namely, a high degree of
      toxicity and unwanted effects, lack of availability and/or problematic
      application under the life conditions of affected populations. Development of
      new, safe and affordable drugs is therefore an urgent need. Nature has provided
      an innumerable number of drugs for the treatment of many serious diseases. Among
      the natural sources for new bioactive chemicals, plants are still predominant.
      Their secondary metabolism yields an immeasurable wealth of chemical structures
      which has been and will continue to be a source of new drugs, directly in their
      native form and after optimization by synthetic medicinal chemistry. The current
      review, published in two parts, attempts to give an overview on the potential of
      such plant-derived natural products as antiprotozoal leads and/or drugs in the
      fight against NTDs.

PMID- 22414102
TI  - Anti-inflammatory iridoids of botanical origin.
AB  - Inflammation is a manifestation of a wide range of disorders which include;
      arthritis, atherosclerosis, Alzheimer's disease, inflammatory bowel syndrome,
      physical injury and infection amongst many others. Common treatment modalities
      are usually nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin,
      paracetamol, indomethacin and ibuprofen as well as corticosteroids such as
      prednisone. These however, may be associated with a host of side effects due to
      non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and
      those with selectivity may be highly priced. Thus, there is a continuing search
      for safe and effective antiinflammatory molecules from natural sources. Research
      has confirmed that iridoids exhibit promising anti-inflammatory activity which
      may be beneficial in the treatment of inflammation. Iridoids are secondary
      metabolites present in various plants, especially in species belonging to the
      Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae
      families. Many of these ethnobotanicals have an illustrious history of
      traditional use alluding to their use to treat inflammation. Although iridoids
      exhibit a wide range of pharmacological activities such as cardiovascular,
      hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour,
      antiviral, immunomodulation and purgative effects this review will acutely focus
      on their anti-inflammatory properties. The paper aims to present a summary for
      the most prominent iridoid-containing plants for which anti-inflammatory activity
      has been demonstrated in vitro and / or in vivo.

PMID- 22414104
TI  - The potential of secondary metabolites from plants as drugs or leads against
      protozoan neglected diseases - part II.
AB  - Infections with protozoan parasites are a major cause of disease and mortality in
      many tropical countries of the world. Diseases caused by species of the genera
      Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania
      (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical
      Diseases" (NTDs) defined by the WHO. Furthermore, malaria (caused by various
      Plasmodium species) can be considered a neglected disease in certain countries
      and with regard to availability and affordability of the antimalarials. Living
      organisms, especially plants, provide an innumerable number of molecules with
      potential for the treatment of many serious diseases. The current review attempts
      to give an overview on the potential of such plant-derived natural products as
      antiprotozoal leads and/or drugs in the fight against NTDs. In part I, a general
      description of the diseases, the current state of therapy and need for new
      therapeuticals, assay methods and strategies applied in the search for new plant
      derived natural products against these diseases and an overview on natural
      products of terpenoid origin with antiprotozoal potential were given. The present
      part II compiles the current knowledge on natural products with antiprotozoal
      activity that are derived from the shikimate pathway (lignans, coumarins, caffeic
      acid derivatives), quinones of various structural classes, compounds formed via
      the polyketide pathways (flavonoids and related compounds, chromenes and related
      benzopyrans and benzofurans, xanthones, acetogenins from Annonaceae and
      polyacetylenes) as well as the diverse classes of alkaloids. In total, both parts
      compile the literature on almost 900 different plant-derived natural products and
      their activity data, taken from over 800 references. These data, as the result of
      enormous efforts of numerous research groups world-wide, illustrate that plant
      secondary metabolites represent an immensely rich source of chemical diversity
      with an extremely high potential to yield a wealth of lead structures towards new
      therapies for NTDs. Only a small percentage, however, of the roughly 200,000
      plant species on earth have been studied chemically and only a small percentage
      of these plants or their constituents has been investigated for antiprotozoal
      activity. The repository of plant-derived natural products hence deserves to be
      investigated even more intensely than it has been up to present.

PMID- 22414105
TI  - Nature against depression.
AB  - Depression is a major health problem currently recognized as a leading cause of
      morbidity worldwide. In the United States alone, depression affects approximately
      20% of the population. With current medications suffering from major shortcomings
      that include slow onset of action, poor efficacy, and unwanted side effects, the
      search for new and improved antidepressants is ever increasing. In an effort to
      evade side effects, people have been resorting to popular traditional herbal
      medicines to relieve the symptoms of depression, and there is a need for more
      empirical knowledge about their use and effectiveness. This review provides an
      overview of the current knowledge state regarding a variety of natural plant
      products commonly used in depression. Herbal medicines discussed that have been
      used in clinical trials for the treatment of mild to moderate depression states
      include the popular St. John's wort, saffron, Rhodiola, lavender, Echium, and the
      Chinese formula banxia houpu. In addition, new emerging herbal products that have
      been studied in different animal models are discussed including Polygala
      tenuifolia, the traditional Chinese herbal SYJN formula, gan mai da zao, and
      Cannabis sativa constituents. A comprehensive review of the chemical,
      pharmacological, and clinical aspects of each of the reviewed products is
      provided. Finally, recent preclinical studies reporting the antidepressant action
      of marine-derived natural products are discussed at the end of the review.

PMID- 22414106
TI  - Phytochemicals from plants to combat cardiovascular disease.
AB  - For many decades, the use of synthetic chemicals as drugs has been effective in
      the treatment of most diseases. Moreover, from ancient to modern history, many
      traditional plant based medicines are playing an important role in health care.
      Phytochemicals are natural bioactive compounds found in vegetables, fruits,
      medicinal plants, aromatic plants, leaves, flowers and roots which act as a
      defense system to combat against diseases. The phytochemicals from natural
      products cover a diverse range of chemical entities such as polyphenols,
      flavonoids, steroidal saponins, organosulphur compounds and vitamins. A number of
      bioactive compounds generally obtained from terrestrial plants such as
      isoflavones, diosgenin, resveratrol, quercetin, catechin, sulforaphane,
      tocotrienols and carotenoids are proven to reduce the risk of cardiovascular
      diseases and aid in cardioprotection which is the leading cause of death
      globally. The cardioprotective effects of the various phytochemicals are perhaps
      due to their antioxidative, antihypercholesteroemic, antiangiogenic, anti
      ischemic, inhibition of platelet aggregation and anti inflammatory activities
      that reduce the risk of cardiovascular disorders. The multi-faceted role of the
      phytochemicals is mediated by its structure-function relationship and can be
      considered as leads for cardiovascular drug design in future. This review
      summarizes the findings of recent studies on selected phytochemicals as
      prophylactic and therapeutic agents in cardioprotection.

PMID- 22414107
TI  - Current concepts on selected plant secondary metabolites with promising
      inhibitory effects against enzymes linked to Alzheimer's disease.
AB  - Alzheimer's disease (AD) has become one of the deadliest diseases for human
      beings with special incidence in elderly population. It is a progressive
      neurodegenerative disease and the most prevalent cause of dementia. The
      neuropathology of AD has not been fully elucidated yet, however, cholinergic
      hypothesis is the most accepted theory nowadays, resulting from the cholinergic
      deficit emerging in the brains of AD patients. Shortage of the neurotransmitters,
      acetylcholine and butyrylcholine has been demonstrated, and therefore, inhibition
      of the enzymes; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) that
      break down acetylcholine and butyrylcholine has become a standard approach for AD
      treatment. However, cholinesterase inhibitors are only effective in symptomatic
      treatment and have no ability to impede the disease. The pathogenesis of AD is
      highly complex and another hypothesis is the formation of amyloid plaques
      containing beta-amyloid peptide, which causes neurolesions in the brains of AD
      patients. Beta-amyloid peptide is generated after the sequential cleavage of
      amyloid precursor protein, especially by the beta- and gamma-secretase in the
      amyloidogenic pathway. The secretases involved in the processing of amyloid
      precursor protein are of particular interest and, consequently, the inhibition of
      secretase enzyme family of protease type has become another desired treatment
      strategy for AD. On the other hand, medicinal plants are attractive sources for
      drug research and development as they produce chemically-varying molecules with
      preferred biological activities. The aim of this article is to review the
      available data on selected inhibitors from plant secondary metabolites with
      emphasis on cholinesterase, prolyl endopeptidase, and secretase enzyme families
      as being the current treatments of AD.

PMID- 22414108
TI  - Novel tyrosinase inhibitors from natural resources - their computational studies.
AB  - Tyrosinase is a multi-copper enzyme widely distributed in different organisms,
      including plants & mammals, etc., which is responsible for pigmentations,
      undesired browning of fruits and vegetables. This is the key enzyme in the
      melanogenesis in human and molting process of insects. Therefore the inhibitors
      of the enzyme may lead to novel skin whitening agents, anti-browning substances
      or compounds for insect control. A large numbers of moderate to potent tyrosinase
      inhibitors have been reported during the last decade. From our group, we reported
      a number of potent inhibitors from synthetic, semi-synthetic and natural origins.
      The compounds are from several chemical classes, like phenolics, terpenes,
      steroids, chalcones, flavonoids, alkaloids, long-chain fatty acids, coumarins,
      sildenafil analogs, bipiperidines, biscoumarins, oxadiazole, tetraketones, etc.
      More recently, the crystal structure of mushroom and couple of other tyrosinases
      has been published and more recently the crystal structure of mushroom tyrosinase
      complexes with a highly potent inhibitor tropolone has been reported. Yet there
      is a lack of information of inhibitor-tyrosinase intermolecular interactions. To
      overcome such issues, some researchers started utilizing in silico tools, like
      molecular docking simulations, for such purposes. There are also few papers
      published about the successful utilization of computational tools like QSAR-based
      and ligand-based virtual screening to identify novel and potent inhibitors of the
      enzyme. In our group, we are using all possible computational tools, like ligand
      based as well structure-based approaches, to identify new inhibitors. In this
      review, some of such examples are briefly described.

PMID- 22414109
TI  - Modulation of k-Ras signaling by natural products.
AB  - Ras proteins regulate diverse cellular pathways that are important in the growth
      and spread of malignancies, including cell proliferation, cell cycle regulation,
      cell survival, angiogenesis and cell migration. These proteins lack the
      conventional transmembrane or hydrophobic domain typical of membrane associated
      proteins. Being small and hydrophilic in nature, these proteins undergo four
      stage post-translational lipid modifications viz. prenylation, AAX proteolysis,
      carboxymethylation and palmitoylation for membrane localization which is
      important for their function. Therefore, enzymes involved in these modifications
      viz. farnesyl transferase (FTase), geranylgeranyl transferase-I (GGTase-I),
      geranylgeranyl transferase-II (GGTase-II), Ras converting enzyme-1 (Rce-1) and
      isoprenyl cysteine methyl transferase (ICMT) are emerging as potential
      therapeutic targets for the discovery of newer anticancer therapeutics. Several
      natural products have shown modulation of these post-translational enzymes. In
      the present review, natural products isolated from terrestrial as well as marine
      sources showing ability to modulate these k-Ras post-translational targets and
      their promise as potential anticancer agents have been discussed. A total of 157
      natural products with 141 corresponding references have been covered.

PMID- 22414110
TI  - Chios gum mastic: A review of its biological activities.
AB  - The resin of Pistacia lentiscus (L.) var. chia (Duham), an evergreen shrub
      belonging to the family Anacardiaceae and uniquely cultivated in southern Chios,
      is known as mastic. It has been used for more than 2500 years in traditional
      Greek medicine for treating several diseases such as gastralgia and peptic
      ulcers, while the actions of the gum are mentioned in the works of Herodotus,
      Dioscorides and Galen. Several Roman, Byzantine, Arab and European authors make
      extensive references to mastic's healing properties. Modern scientific research
      has justified the beneficial action of mastic to gastric diseases, by revealing
      its in vivo and in vitro activity against Helicobacter pylori, which is
      considered as the main cause for gastric ulcers. Furthermore, studies of the
      antimicrobial, antifungal, antioxidant, hypolipidemic, anti-inflammatory, anti
      Crohn and anticancer activities of mastic have characterized it as a wide-range
      therapeutic agent and a potential source of nature-originated treatments.

PMID- 22414112
TI  - Physical activity of children with cerebral palsy: what are the considerations?

PMID- 22414111
TI  - Automatic single-trial discrimination of mental arithmetic, mental singing and
      the no-control state from prefrontal activity: toward a three-state NIRS-BCI.
AB  - BACKGROUND: Near-infrared spectroscopy (NIRS) is an optical imaging technology
      that has recently been investigated for use in a safe, non-invasive brain
      computer interface (BCI) for individuals with severe motor impairments. To date,
      most NIRS-BCI studies have attempted to discriminate two mental states (e.g., a
      mental task and rest), which could potentially lead to a two-choice BCI system.
      In this study, we attempted to automatically differentiate three mental states -
      specifically, intentional activity due to 1) a mental arithmetic (MA) task and 2)
      a mental singing (MS) task, and 3) an unconstrained, "no-control (NC)" state - to
      investigate the feasibility of a three-choice system-paced NIRS-BCI. RESULTS:
      Deploying a dual-wavelength frequency domain near-infrared spectrometer, we
      interrogated nine sites around the frontopolar locations while 7 able-bodied
      adults performed mental arithmetic and mental singing to answer multiple-choice
      questions within a system-paced paradigm. With a linear classifier trained on a
      ten-dimensional feature set, an overall classification accuracy of 56.2% was
      achieved for the MA vs. MS vs. NC classification problem and all individual
      participant accuracies significantly exceeded chance (i.e., 33%). However, as
      anticipated based on results of previous work, the three-class discrimination was
      unsuccessful for three participants due to the ineffectiveness of the mental
      singing task. Excluding these three participants increases the accuracy rate to
      62.5%. Even without training, three of the remaining four participants achieved
      accuracies approaching 70%, the value often cited as being necessary for
      effective BCI communication. CONCLUSIONS: These results are encouraging and
      demonstrate the potential of a three-state system-paced NIRS-BCI with two
      intentional control states corresponding to mental arithmetic and mental singing.

PMID- 22414113
TI  - Divergent physiological characteristics and responses to endurance training among
      inbred mouse strains.
AB  - Both baseline values and adaptive changes in mice can vary depending on the
      genetic background. We aimed to assess variation in a battery of variables and
      their adaptations to endurance training in six inbred mouse strains. Males, n =
      184, from A/J, BALB/cByJ, C3H/HeJ, C57BL/6J, DBA/2J, and PWD/PhJ strains were
      assigned to a control or an endurance group (5 weeks swimming exercise). Enzyme
      activity, histology of soleus (SOL) muscle, swimming endurance, cardiac
      ventricular and hind limb muscle weight, and femur length were examined.
      Endurance capacity, morphological and histological variables, and enzyme activity
      substantially differed among strains. For example, SOL weight was twofold higher
      and cross-sectional area (CSA) of fibers was ~ 30% greater in C57BL/6J than in
      PWD/PhJ strain. The CSA of type 1 fibers were larger than type 2A in PWD/PhJ (P <
      0.01); however, the reverse was true in DBA/2J and BALB/cByJ strains (P < 0.05).
      Swimming endurance in DBA/2J strain was ~ 9 times better than in BALB/cByJ.
      Endurance training increased the activity of citrate synthase in gastrocnemius
      across strains (P < 0.01), however, changes in endurance were strain-specific;
      the C57BL/6J and DBA/2J strains improved substantially, whereas A/J and BALB/cByJ
      strains did not. In conclusion, genetic background is a potent determinant of the
      physiological characteristics and adaptations to training in mice.

PMID- 22414114
TI  - Design of experiments utilization to map the processing capabilities of a micro
      spray dryer: particle design and throughput optimization in support of drug
      discovery.
AB  - There has been a growing interest in amorphous solid dispersions for
      bioavailability enhancement in drug discovery. Spray drying, as shown in this
      study, is well suited to produce prototype amorphous dispersions in the Candidate
      Selection stage where drug supply is limited. This investigation mapped the
      processing window of a micro-spray dryer to achieve desired particle
      characteristics and optimize throughput/yield. Effects of processing variables on
      the properties of hypromellose acetate succinate were evaluated by a fractional
      factorial design of experiments. Parameters studied include solid loading,
      atomization, nozzle size, and spray rate. Response variables include particle
      size, morphology and yield. Unlike most other commercial small-scale spray
      dryers, the ProCepT was capable of producing particles with a relatively wide
      mean particle size, ca. 2-35 um, allowing material properties to be tailored to
      support various applications. In addition, an optimized throughput of 35 g/hour
      with a yield of 75-95% was achieved, which affords to support studies from Lead
      identification/Lead-optimization to early safety studies. A regression model was
      constructed to quantify the relationship between processing parameters and the
      response variables. The response surface curves provide a useful tool to design
      processing conditions, leading to a reduction in development time and drug usage
      to support drug discovery.

PMID- 22414116
TI  - Rasch analysis of items from two self-report measures of motor function:
      determination of item difficulty and relationships with children's ability
      levels.
AB  - AIM: The aim of this article was to determine item measurement properties of a
      set of items selected from the Gillette Functional Assessment Questionnaire (FAQ)
      and the Pediatric Outcome Data Collection Instrument (PODCI) using Rasch
      analysis, and to explore relationships between the FAQ/PODCI combined set of
      items, FAQ walking scale level, Gross Motor Function Classification System
      (GMFCS) levels, and the Gait Deviation Index on a common measurement scale.
      METHOD: Rasch analysis was performed on data from a retrospective chart review of
      parent-reported FAQ and PODCI data from 485 individuals (273 males; 212 females;
      mean age 9 y 10 mo, SD 3 y 10 mo) who underwent first-time three-dimensional gait
      analysis. Of the 485 individuals, 289 had a diagnosis of cerebral palsy (104
      GMFCS level I, 97 GMFCS level II, 69 GMFCS level III, and 19 GMFCS level IV).
      Rasch-based person abilities and item difficulties based on subgroups defined by
      the FAQ walking scale level, Gait Deviation Index, and the GMFCS level were
      compared. RESULTS: The FAQ/PODCI item set demonstrated necessary Rasch
      characteristics to support its use as a combined measurement scale. Item
      groupings at similar difficulty levels were consistent with the mean person
      abilities of subgroups based on FAQ walking scale level, Gait Deviation Index,
      and GMFCS level. INTERPRETATION: Rasch-derived person ability scores from the
      FAQ/PODCI combined item set are consistent with clinical measures. Rasch analysis
      provides insights that may improve interpretation of the difficulty of motor
      functions for children with disabilities.

PMID- 22414115
TI  - Colorectal cancer risk assessment and screening recommendation: a community
      survey of healthcare providers' practice from a patient perspective.
AB  - BACKGROUND: Family history is a common risk factor for colorectal cancer (CRC),
      yet it is often underused to guide risk assessment and the provision of risk
      appropriate CRC screening recommendation. The aim of this study was to identify
      from a patient perspective health care providers' current practice relating to:
      (i) assessment of family history of CRC; (ii) notification of "increased risk" to
      patients at "moderately/potentially high" familial risk; and (iii) recommendation
      that patients undertake CRC screening. METHODS: 1592 persons aged 56-88 years
      randomly selected from the Hunter Community Study (HCS), New South Wales,
      Australia were mailed a questionnaire. 1117 participants (70%) returned a
      questionnaire. RESULTS: Thirty eight percent of respondents reported ever being
      asked about their family history of CRC. Ever discussing family history of CRC
      with a health care provider was significantly more likely to occur for persons
      with a higher level of education, who had ever received screening advice and with
      a lower physical component summary score. Fifty one percent of persons at
      "moderately/potentially high risk" were notified of their "increased risk" of
      developing CRC. Thirty one percent of persons across each level of risk had ever
      received CRC screening advice from a health care provider. Screening advice
      provision was significantly more likely to occur for persons who had ever
      discussed their family history of CRC with a health care provider and who were at
      "moderately/potentially high risk". CONCLUSIONS: Effective interventions that
      integrate both the assessment and notification of familial risk of CRC to the
      wider population are needed. Systematic and cost-effective mechanisms that
      facilitate family history collection, risk assessment and provision of screening
      advice within the primary health care setting are required.

PMID- 22414117
TI  - Synthesis of substituted 1H-indazoles from arynes and hydrazones.
AB  - The 1H-indazole skeleton can be constructed by a [3 + 2] annulation approach from
      arynes and hydrazones. Under different reaction conditions, both N
      tosylhydrazones and N-aryl/alkylhydrazones can be used to afford a variety of
      indazoles. The former reaction affords 3-substituted indazoles either via in situ
      generated diazo compounds or through an annulation/elimination process. The
      latter reaction leads to 1,3-disubstituted indazoles likely through an
      annulation/oxidation process. The reactions operate under mild conditions and can
      accommodate aryl, vinyl, and less satisfactorily, alkyl groups.

PMID- 22414118
TI  - Foreword: V International EURAIBI meeting brain injury and neonatal diseases:
      early diagnosis and therapeutic strategies.

PMID- 22414119
TI  - On the deactivation mechanisms of adenine-thymine base pair.
AB  - In this contribution, the multiconfigurational second-order perturbation theory
      method based on a complete active space reference wave function (CASSCF/CASPT2)
      is applied to study all possible single and double proton/hydrogen transfers
      between the nucleobases in the adenine-thymine (AT) base pair, analyzing the role
      of excited states with different nature [localized (LE) and charge transfer
      (CT)], and considering concerted as well as step-wise mechanisms. According to
      the findings, once the lowest excited states, localized in adenine, are populated
      during UV irradiation of the Watson-Crick base pair, the proton transfer in the N
      O bridge does not require high energy in order to populate a CT state. The latter
      state will immediately relax toward a crossing with the ground state, which will
      funnel the system to either the canonical structure or the imino-enol tautomer.
      The base pair is also capable of repairing itself easily since the imino-enol
      species is unstable to thermal conversion.

PMID- 22414120
TI  - Road Safety in 10 Countries: a global opportunity.

PMID- 22414121
TI  - The importance of data for global road safety.

PMID- 22414122
TI  - Quantifying the underestimated burden of road traffic mortality in Mexico: a
      comparison of three approaches.
AB  - INTRODUCTION: We present a novel multistep technique to estimate the actual
      burden of road traffic mortality in Mexico during the time period 1999 to 2009 by
      comparing 3 approaches for redistribution of nonspecific ("garbage")
      International Classification of Diseases (ICD)-coded deaths. METHODS: Road
      traffic (RT) mortality data were extracted using a secondary analysis of the
      Mexican mortality databases for the period 1999 to 2009. In an attempt to correct
      for underestimation due to inappropriately coded deaths, those deaths assigned to
      nonspecific codes were redistributed utilizing 3 different adjustment methods. A
      comparison of the 3 adjustment approaches (proportional, multiple imputation, and
      regression) is presented. A Poisson regression analysis was utilized to model
      mortality trends in the raw data and the 3 estimates. RESULTS: After adjustments,
      the total number of RT deaths increased by 18 to 45 percent, showing significant
      underestimation when only the raw data are used. All 3 approaches showed
      statistically significantly higher RT mortality rates than the crude figures. The
      proportional approach resulted in the highest RT mortality rate estimate of 23
      per 100,000 in 2009 and showed a statistically significant positive increase of
      1.5 percent per year across the decade. The 60+ age group and pedestrians had the
      highest mortality rates of 40 and 10.3 per 100,000, respectively. Over the
      decade, there was an alarming 332 percent increase in the mortality rate for male
      motorcyclists. CONCLUSION: Though efforts to improve coding should continue to be
      implemented, we present an additional and often overlooked contribution to the
      underestimation of road traffic mortality: the ICD nonspecific codes. Improved
      estimates of road traffic mortality are important in Mexico for policy change and
      decision making, highlighting the importance of targeting road traffic deaths as
      a public health problem. The approach presented here may also be useful for
      estimating the burden of other deaths with similar coding problems.

PMID- 22414124
TI  - Evidence-based road safety practice in India: assessment of the adequacy of
      publicly available data in meeting requirements for comprehensive road safety
      data systems.
AB  - OBJECTIVE: To assess the availability and coverage of publicly available road
      safety data at the national and state levels in India. METHODS: We reviewed the 2
      publicly accessible data sources in India for the availability of data related to
      traffic injuries and deaths: (1) the National Crime Records Bureau (NCRB) and (2)
      the Ministry of Road Transport and Highways (MORTH). Using the World Health
      Organization (WHO) manual for the comprehensive assessment of road safety data,
      we developed a checklist of indicators required for comprehensive road safety
      assessment. These indicators were then used to assess the availability of road
      safety data in India using the NCRB and MORTH data. We assessed the availability
      of data on outcomes and exposures indicators (i.e., number of crashes, injuries,
      deaths, timing of deaths, gender and age distribution of injuries and deaths),
      safety performance indicators (i.e., with reference to select risk factors of
      speeding, alcohol, and helmet use), and cost indicators (i.e., medical costs,
      material costs, intervention costs, productivity costs, time costs, and losses to
      quality of life). RESULTS: Information on outcome indicators was the most
      comprehensive in terms of availability. Both NCRB and MORTH databases had data
      for most of the need areas specified by the WHO under outcomes and exposure
      indicators. Regarding outcome and exposure indicators, data were available for 81
      and 91 percent of specified need areas at the national level from NCRB and MORTH
      databases, respectively. At the state level, data on outcome and exposure
      indicators were available for only 54 percent of need areas from either of the 2
      sources. There were no data on safety performance indicators in the NCRB
      database. From the MORTH database, data availability on safety performance
      indicators was 60 percent at both national and state levels. Data availability on
      costs and process indicators was found to be below 20 percent at the national and
      state levels. CONCLUSION: Overall, there is an urgent need to improve the
      publicly available road safety data in India. This will enhance monitoring of the
      burden of traffic injuries and deaths, enable sound interpretation of national
      road safety data, and allow the formulation effective road safety policies.

PMID- 22414123
TI  - Road traffic deaths in Brazil: rising trends in pedestrian and motorcycle
      occupant deaths.
AB  - OBJECTIVE: According to the World Health Organization, the global burden of road
      traffic mortality exceeds 1.27 million people annually; over 90 percent occur in
      low- and middle-income countries. Brazil's road traffic mortality rate of ~20 per
      100,000 is significantly higher than nearby Chile or Argentina. To date, there
      has been very little information published on road traffic fatalities among
      vulnerable road users (VRUs) in Brazil. METHODS: Road traffic fatality data from
      2000 to 2008 were extracted from Brazil's Mortality Information System (SIM).
      Road traffic deaths were extracted using the International Classification of
      Diseases (ICD-10) V-codes (V01-V89) and then subcategorized by VRU categories.
      Information was then disaggregated by gender, age, and region. RESULTS: In 2008,
      39,211 deaths due to road traffic injuries were recorded in Brazil, resulting in
      a crude mortality rate of 20.7 per 100,000 inhabitants. Pedestrian mortality
      averaged 5.46 deaths per 100,000 between 2000 and 2008. The mortality rate for
      elderly pedestrians (80+ years) is 20.1 per 100,000, over 10 times that of 0- to
      9-year-olds. In the past decade, motorcycle occupant mortality has dramatically
      increased by over 300 percent from 1.5 per 100,000 in 2000 to 4.7 per 100,000 in
      2008. The 20- to 29-year age group remains most affected by motorcycle deaths,
      with a peak fatality rate of 10.76 per 100,000 in 2008. The north and northeast
      regions, with the lower per capita gross domestic product (GDP), have higher
      proportions of VRU deaths compared with other regions. CONCLUSIONS: Vulnerable
      road users are contributing an increasing proportion of the road traffic
      fatalities in Brazil. Nationally, elderly pedestrians are at particularly high
      risk and motorcycle fatalities are increasing at a rapid rate. Less prosperous
      regions have higher proportions of VRU deaths. Understanding the epidemiology of
      road traffic mortality in vulnerable road user categories will better allow for
      targeted interventions to reduce these preventable deaths.

PMID- 22414125
TI  - Road traffic injuries in Kenya: the health burden and risk factors in two
      districts.
AB  - BACKGROUND: Road traffic injuries (RTIs) contribute to a significant proportion
      of the burden of disease in Kenya. They also have a significant impact on the
      social and economic well-being of individuals, their families, and society.
      However, though estimates quantifying the burden of RTIs in Kenya do exist, most
      of these studies date back to the early 2000s-more than one decade ago.
      OBJECTIVE: This article aims to present the current status of road safety in
      Kenya. Using data from the police and vital registration systems in Kenya, we
      present the current epidemiology of RTIs in the nation. We also sought to assess
      the status of 3 well-known risk factors for RTIs-speeding and the use of helmets
      and reflective clothing. METHODS: Data for this study were collected in 2 steps.
      The first step involved the collection of secondary data from the Kenya traffic
      police as well as the National Vital Registration System to assess the current
      trends of RTIs in Kenya. Following this, observational studies were conducted in
      the Thika and Naivasha districts in Kenya to assess the current status of
      speeding among all vehicles and the use of helmets and reflective clothing among
      motorcyclists. RESULTS: The overall RTI rate in Kenya was 59.96 per 100,000
      population in 2009, with vehicle passengers being the most affected. Notably,
      injuries to motorcyclists increased at an annual rate of approximately 29 percent
      (95% confidence interval [CI]: 27-32; P < .001). The mean age of death due to
      road traffic crashes was 35 years. Fatalities due to RTIs increased at an annual
      rate of 7 percent (95% CI: 6-8; P < .001) for the period 2004 to 2009.
      Observational studies revealed that 69.45 percent of vehicles in Thika and 34.32
      percent of vehicles in Naivasha were speeding. Helmets were used by less than one
      third of motorcycle drivers in both study districts, with prevalence rates
      ranging between 3 and 4 percent among passengers. CONCLUSIONS: This study
      highlights the significant burden of RTIs in Kenya. A renewed focus on addressing
      this burden is necessary. Focusing on increasing helmet and reflective clothing
      use and enforcement of speed limits has the potential to prevent a large number
      of road traffic crashes, injuries, and fatalities. However, it is difficult to
      demonstrate the magnitude of the injury problem to policymakers with minimal or
      inaccurate data, and this study illustrates the need for national continuous,
      systematic, and sustainable data collection efforts, echoing similar calls for
      action throughout the injury literature.

PMID- 22414126
TI  - Helmet use among motorcyclists in Cambodia: a survey of use, knowledge,
      attitudes, and practices.
AB  - OBJECTIVE: Road traffic injuries (RTIs) are a leading cause of disability and
      fatality globally. Motorcycle-related injuries, mainly head injuries, and related
      deaths and disabilities are a significant contributor to the burden of disease in
      low- and middle-income countries (LMICs). Helmets have been proven to be an
      effective way to reduce the risk of head injury. As motorcycle use continually
      increases in Cambodia, head injuries and related deaths and disabilities are
      expected to rise. This article aims to assess the current status of helmet use in
      Cambodia, as well as the knowledge, attitudes, and practices among motorcyclists,
      in order to assist with better planning and implementation of injury prevention
      strategies. METHODS: Two separate methodologies were employed for this study.
      Helmet observations were conducted in Phnom Penh, Kandal, Kampong Speu, Siem
      Reap, and Kampong Cham to assess the current status of helmet use during the day
      and at night. Roadside knowledge, attitudes, and practice (KAP) interviews were
      also conducted in Phnom Penh, Kandal, and Kampong Speu to determine the
      prevailing beliefs around helmet use in Cambodia. RESULTS: Based on observations,
      the proportion of helmet wearing across all study sites was 25 percent at night
      and 43 percent during the day among all motorcyclists. The observed proportion
      was up to 10 times higher among drivers compared to passengers. The top 3 reasons
      for always wearing a helmet were lifesaving potential, legal duty, and police
      fines. Almost 60 percent of respondents said that their use or nonuse of a helmet
      depended on where they were driving. Helmet quality, price, style, and color were
      important factors influencing the decision to purchase a helmet. CONCLUSIONS: A
      paradox appears to exist in Cambodia; though awareness of the benefits of wearing
      a helmet is high, actual helmet use remains low in the country. Daytime usage is
      higher than nighttime, and these proportions are significantly higher among
      drivers compared to passengers. There is a continuing need to improve the
      proportion of all-day helmet wearing, especially at night and among motorcycle
      passengers in Cambodia.

PMID- 22414127
TI  - Drinking and driving in Vietnam: public knowledge, attitudes, and practices.
AB  - OBJECTIVE: Injuries are among the 10 leading causes of death for all ages in
      Vietnam, and road traffic fatalities account for approximately half of those
      deaths. Despite having what is considered to be one of the most stringent alcohol
      legislations in the region, alcohol involvement in road traffic crashes remains
      high. This study aims to illustrate the knowledge, attitudes, and practices
      around alcohol use and drinking and driving by age and sex in 3 provinces in
      Vietnam. METHODS: This study was conducted between January and February 2011,
      surveying randomly selected road users over the age of 17 years at gas stations
      in 3 provinces: Ha Nam, Ninh Binh, and Bac Giang, Vietnam. Data were collected
      for one week at each gas station. A knowledge, attitudes, and practices (KAPs)
      survey was administered in 7 time blocks of 90 min throughout the day, from 07:30
      am to 9:30 pm. RESULTS: There were a total of 633 respondents almost evenly
      divided among the 3 provinces. Males accounted for 69.1 percent of respondents;
      the majority were 36 years of age or younger. Despite the belief that drinking
      and driving will increase the risk of a crash, a significant proportion of
      respondents (44.9%) reported drinking and driving; 56.7 percent admitted to
      drinking and driving within the last month. Drinking and driving was more common
      among males, with approximately 60.2 percent indicating a history of drinking and
      driving. This proportion was particularly high among males aged 17 to 26 (71.4%).
      It was found that preferred alternatives to drinking and driving when available
      were leaving with a nondrinker (42%), resting until "feeling conscious" (23%),
      and drinking less (20%). CONCLUSIONS: This study shows that, in general, alcohol
      use and drinking and driving remain a problem in Vietnam, a major concern given
      that the country is rapidly motorizing and likewise increasing the likelihood of
      road traffic crashes in the absence of effective interventions. To target
      drinking and driving in Vietnam we call for a multifaceted approach, including
      social marketing and public education campaigns, enhanced enforcement, and
      programs that either limit the number of drinks to drivers or young individuals
      or those that provide alternatives to drinking and driving.

PMID- 22414128
TI  - Road traffic injuries and data systems in Egypt: addressing the challenges.
AB  - OBJECTIVE: Road traffic injuries (RTIs) are a major cause of global mortality and
      morbidity, killing approximately 1.3 million people and injuring 20 to 50 million
      each year. The significance of this public health threat is most pronounced in
      low- and middle-income countries where 90 percent of the world's road traffic
      related fatalities take place. Current estimates for Egypt show a road traffic
      fatality rate of 42 deaths per 100,000 population-one of the highest in the
      Eastern Mediterranean Region. RTIs are also responsible for 1.8 percent of all
      deaths and 2.4 percent of all disability-adjusted life years (DALYs) lost in the
      country. Despite this, studies surrounding this topic are scarce, and reliable
      data are limited. The overall goal of this article is to define the health impact
      of RTIs in Egypt and to identify the strengths and weaknesses of each data source
      for the purpose of improving the current RTI data systems. METHODS: A 2-pronged
      approach was undertaken to assess the burden of RTIs in Egypt. First, a thorough
      literature review was performed using PubMed, Embase, ISIS Web of Knowledge, and
      Scopus databases. Articles pertaining to Egypt and road traffic injuries were
      selected for screening. With assistance from Egyptian colleagues, a comprehensive
      exploration of data sources pertaining to RTIs in Egypt was undertaken and
      secondary data from these sources were procured for analysis. RESULTS: The
      literature review yielded a total of 20 studies, of which 6 were multi-country
      and 5 were hospital-based studies. None examined risk factors such as speeding,
      alcohol, or seat belt use. Secondary data sources were acquired from national
      hospital-based injury surveillance; a community-based health survey; pre-hospital
      injury surveillance; the Ministry of Transport; the General Authority for Roads,
      Bridges and Land Transport; death certificates; and the central agency for public
      motorization and statistics. Risk factor data are also limited from these
      sources. CONCLUSION: The results of this article clearly highlight the
      significant burden that road traffic injuries pose on the health of the Egyptian
      population. The hospital-based injury surveillance system that has been
      established in the country and the use of International Classification of
      Diseases (ICD-10) coding brings the system very closely in line with
      international guidelines. There is, however, some considerable room for
      improvement, including the need to extend the coverage of the surveillance
      system, the inclusion of injury severity scores and disability indicators, and
      standardization of the sometimes rather disparate sources from various sectors in
      order to maximally capture the true burden of RTIs.

PMID- 22414129
TI  - Road traffic injury in China: a review of national data sources.
AB  - OBJECTIVE: Road traffic injury (RTI) has become one of the leading causes of
      deaths in China, yet numbers on road traffic deaths are often inconsistent. This
      study sought to systematically review 4 national-level data sources that can be
      used to estimate burdens of RTI, including mortality, injury, and crashes in
      China. METHODS: We conducted structured literature reviews in PubMed, using
      combined key words of injury or fatality or injury surveillance and traffic and
      China in order to identify relevant studies (in both English and Chinese) and
      data sources. We also conducted interviews and hosted seminars with key
      researchers from the Chinese Center for Disease Control and Prevention (Chinese
      CDC) to identify potential useful data sources for injury surveillance. We then
      extracted key information from publicly available reports of each data source.
      RESULTS: Four national-level data sources were reviewed and compared: Ministry of
      Health-Vital Registration (MOH-VR) System, Chinese CDC-Disease Surveillance
      Points (DSP), Chinese CDC-National Injury Surveillance System (NISS), and police
      reports. Together they provide a complementary yet somewhat contradictory
      epidemiological profile of RTIs in China. Estimates on road traffic fatalities
      obtained from MOH-VR and police reports are often used by researchers and
      policymakers, whereas DSP and NISS, both with great merits, have virtually not
      been used for RTI research. Despite the well-documented problems of underreported
      deaths with both MOH-VR and DSP, estimated road traffic deaths from both systems
      were 3 times those reported by the police. CONCLUSIONS: As the foundation of
      injury prevention, national-level data sources and surveillance systems were
      reviewed in the study. Existing data infrastructures present the Chinese
      government a great opportunity to strengthen and integrate existing surveillance
      systems to better track road traffic injury and fatality and identify the
      population at risk.

PMID- 22414130
TI  - Burden of road traffic injuries in Turkey.
AB  - OBJECTIVE: Road traffic injuries (RTIs) are one of the leading causes of global
      deaths, contributing to 1.3 million lives lost each year. Although all regions
      are affected, low- and middle-income countries share a disproportionate burden.
      The significance of this public health threat is growing in Turkey, where current
      estimates show that 2.0 percent of all deaths in the country are due to RTIs.
      Despite the significance of this growing epidemic, data pertaining to RTIs in
      Turkey are limited. In order to address the gap in knowledge, this article
      presents an overview of the epidemiology of RTIs in Turkey through an analysis of
      available secondary data sets and a comprehensive review of scientifically
      published studies. METHODS: A literature review was performed during December
      2010 using PubMed, Embase, and ISIS Web of Knowledge databases and Google search
      engines. Peer-reviewed literature pertaining to Turkey and RTIs were selected for
      screening. Secondary data were also procured with assistance from Turkish
      colleagues through an exploration of data sources pertaining to RTIs in Turkey.
      RESULTS: The literature review yielded a total of 70 studies with publication
      years ranging from 1988 to 2010. Secondary data sources were procured from the
      ministries of Health and Interior as well as the Turkish Statistical Institute.
      These data sources focus primarily on crashes, injuries, and fatalities (crash
      rate of 1328.5 per 100,000 population; injury rate of 257.9 per 100,000
      population; fatality rate of 5.9 per 100,000). Risk factor data surrounding road
      safety are limited. CONCLUSION: The findings reveal the significant burden that
      RTIs pose on the health of the Turkish population. The introduction of new
      technologies such as the novel digital recording systems in place to record pre
      hospital services and Global Positioning System (GPS) tracking of road traffic
      crashes by the police have allowed for a more accurate picture of the burden of
      RTIs in Turkey. There are, however, some considerable gaps and limitations within
      the data systems. Incorporation of standardized definitions, regular data audits,
      and timely review of collated data will improve the utility of RTI data and allow
      it to be used for policy influence.

PMID- 22414131
TI  - Seat belt and child seat use in Lipetskaya Oblast, Russia: frequencies,
      attitudes, and perceptions.
AB  - OBJECTIVE: Despite the importance of understanding seat belt use patterns among
      drivers and passengers for the purpose of direct interventions or monitoring
      improvements, no study has described wearing rates for all seat positions in
      Russia. This study describes observed seat belt use and knowledge, attitudes, and
      perceptions of seat belt use in Lipetskaya Oblast, Russia. METHODS: An
      observational study on the use of seat belts and child restraints in the
      Lipetskaya region conducted during October 2010 collected data in 6 districts and
      on 3 different road types. A roadside survey gathered information on knowledge,
      attitudes, and perceptions toward the use of seat belts from randomly selected
      drivers. Frequencies of seat belt use by seat position, gender, and road type
      were calculated. A multivariable logit model disclosed the associations between
      seat belt use and sociodemographic factors. The study design permitted comparison
      of observed seat belt use to self-reported seat belt use. RESULTS: A total of
      25,795 vehicles and 39,833 drivers and passengers contributed observations.
      Overall, 55 percent of drivers were observed to be using seat belts. More than
      half (58%) of front seat passengers wore seat belts and only 9 percent of back
      seat passengers were observed to be wearing seat belts; 11 percent of cars with
      children had any type of child safety measure. Drivers on urban roads were less
      likely to wear seat belts compared to those on main highways and rural roads.
      Nearly 60 percent of survey respondents mentioned "seat belts save lives," and
      more than half mentioned law requirements and fines. CONCLUSIONS: Although the
      observed seat belt use in Lipetskaya Oblast is much higher than previous
      estimates in Russia, overall wearing rates remain far from universal. Rear seat
      passengers and children are particularly at risk. Because combined education and
      enforcement has proven to be effective elsewhere, such interventions are needed
      to improve seat belt use.

PMID- 22414132
TI  - Projecting the health and economic impact of road safety initiatives: a case
      study of a multi-country project.
AB  - OBJECTIVE: The Road Safety in 10 Countries (RS-10) project will implement 12
      different road safety interventions at specific sites within 10 low- and middle
      income countries (LMICs). This evaluation reports the number of lives that RS-10
      is projected to save in those locations, the economic value of the risk
      reduction, and the maximum level of investment that a public health intervention
      of this magnitude would be able to incur before its costs outweigh its health
      benefits. METHODS: We assumed a 5-year time implementation horizon corresponding
      to the duration of RS-10. Based on a preliminary literature review, we estimated
      the effectiveness for each of the RS-10 interventions. Applying these
      effectiveness estimates to the size of the population at risk at RS-10 sites, we
      calculated the number of lives and life years saved (LYS) by RS-10. We projected
      the value of a statistical life (VSL) in each RS-10 country based on gross
      national income (GNI) and estimated the value of the lives saved using each
      country's VSL. Sensitivity analysis addressed robustness to assumptions about
      elasticity, discount rates, and intervention effectiveness. RESULTS: From the
      evidence base reviewed, only 13 studies met our selection criteria. Such a
      limited base presents uncertainties about the potential impact of the modeled
      interventions. We tried to account for these uncertainties by allowing
      effectiveness to vary +/- 20 percent for each intervention. Despite this
      variability, RS-10 remains likely to be worth the investment. RS-10 is expected
      to save 10,310 lives over 5 years (discounted at 3%). VSL and $/LYS methods
      provide concordant results. Based on our estimates of each country's VSL, the
      respective countries would be willing to pay $2.45 billion to lower these
      fatality risks (varying intervention effectiveness by +/- 20 percent, the
      corresponding range is $2.0-$2.9 billion). Analysis based on $/LYS shows that the
      RS-10 project will be cost-effective as long as its costs do not exceed $5.14
      billion (under +/- 20% intervention effectiveness, the range = $4.1-$6.2
      billion). Even at low efficacy, these estimates are still several orders of
      magnitude above the $125 million projected investment. CONCLUSION: RS-10 is
      likely to yield high returns for invested resources. The study's chief limitation
      was the reliance on the world's limited evidence base on how effective the road
      safety interventions will be. Planned evaluation of RS-10 will enhance planners'
      ability to conduct economic assessments of road safety in developing countries.

PMID- 22414133
TI  - Double-fold C-H oxygenation of arenes using PyrDipSi: a general and efficient
      traceless/modifiable silicon-tethered directing group.
AB  - The efficient Pd-catalyzed double-fold C-H oxygenation of arenes into resorcinols
      using the newly developed 2-pyrimidyldiisopropylsilyl (PyrDipSi) directing group
      is described. Its use allows for the sequential introduction of OAc and OPiv
      groups in a one-pot manner to produce orthogonally protected resorcinol
      derivatives. The PyrDipSi group is superior to the previously developed 2
      pyridyldiisopropylsilyl (PyDipSi) group, as it is efficient for monooxygenation
      of ortho-substituted arenes. Notably, the PyrDipSi group can be easily installed
      into arene molecules and can be easily removed or modified after the oxygenation
      reaction.

PMID- 22414134
TI  - Effects of robotic-assisted laparoscopic prostatectomy on surgical pathology
      specimens.
AB  - BACKGROUND: Robotic-assisted laparoscopic prostatectomy (RALP) has greatly
      changed clinical management of prostate cancer. It is important for pathologists
      and urologists to compare RALP with conventional open radical retropubic
      prostatectomy (RRP), and evaluate their effects on surgical pathology specimens.
      METHODS: We retrospectively reviewed and statistically analyzed 262 consecutive
      RALP (n = 182) and RRP (n = 80) procedures performed in our institution from 2007
      to 2010. From these, 49 RALP and 33 RRP cases were randomly selected for
      additional microscopic examination to analyze the degree of capsular incision and
      the amount of residual prostate surface adipose tissue. RESULTS: Positive
      surgical margins were present in 28.6% RALP and 57.5% RRP cases, a statistically
      significant difference. In patients with stage T2c tumors, which represent 61.2%
      RALP and 63.8% RRP patients, the positive surgical margin rate was 24.1% in the
      RALP group and 58.8% in the RRP group (statistically significant difference). For
      other pathologic stages, the differences in positive margins between RALP and RRP
      groups were not statistically significant. The incidence of positive surgical
      margins after RALP was related to higher tumor stage, higher Gleason score,
      higher tumor volume and lower prostate weight, but was not related to the
      surgeons performing the procedure. When compared with RRP, RALP also caused less
      severe prostatic capsular incision and maintained larger amounts of residual
      surface adipose tissue in prostatectomy specimens. CONCLUSIONS: In this study
      RALP showed a statistically significant lower positive surgical margin rate than
      RRP. Analysis of capsular incision and amount of prostatic surface residual
      adipose tissue suggested that RALP caused less prostatic capsular damage than
      RRP. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1278078279667611.

PMID- 22414136
TI  - Molecular fractionation of dissolved organic matter with metal salts.
AB  - Coagulation of dissolved organic matter (DOM) by hydrolyzing metals is an
      important environmental process with particular relevance, e.g., for the cycling
      of organic matter in metal-rich aquatic systems or the flocculation of organic
      matter in wastewater treatment plants. Often, a nonremovable fraction of DOM
      remains in solution even at low DOM/metal ratios. Because coagulation by metals
      results from interactions with functional groups, we hypothesize that
      noncoagulating fractions have a distinct molecular composition. To test the
      hypothesis, we analyzed peat-derived dissolved organic matter remaining in
      solution after mixing with salts of Ca, Al, and Fe using 15 T Electrospray
      Ionization Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry (ESI-FT
      ICR-MS). Addition of metals resulted in a net removal of DOM. Also a reduction of
      molecular diversity was observed, as the number of peaks from the ESI-FT-ICR-MS
      spectra decreased. At DOM/metal ratios of ~9 Ca did not show any preference for
      distinct molecular fractions, while Fe and Al removed preferentially the most
      oxidized compounds (O/C ratio >0.4) of the peat leachate. Lowering DOM/metal
      ratios to ~1 resulted in further removal of less oxidized as well as more
      aromatic compounds ("black carbon"). Molecular composition in the residual
      solution after coagulation was more saturated, less polar, and less oxidized
      compared to the original peat leachate and exhibited a surprising similarity with
      DOM of marine origin. By identifying more than 9200 molecular formulas we can
      show that structural properties (saturation and aromaticity) and oxygen content
      of individual DOM molecules play an important role in coagulation with metals. We
      conclude that polyvalent cations not only alter the net mobility but also the
      very molecular composition of DOM in aquatic environments.

PMID- 22414135
TI  - Using Rasch rating scale model to reassess the psychometric properties of the
      Persian version of the PedsQLTM 4.0 Generic Core Scales in school children.
AB  - BACKGROUND: Item response theory (IRT) is extensively used to develop adaptive
      instruments of health-related quality of life (HRQoL). However, each IRT model
      has its own function to estimate item and category parameters, and hence
      different results may be found using the same response categories with different
      IRT models. The present study used the Rasch rating scale model (RSM) to examine
      and reassess the psychometric properties of the Persian version of the PedsQLTM
      4.0 Generic Core Scales. METHODS: The PedsQLTM 4.0 Generic Core Scales was
      completed by 938 Iranian school children and their parents. Convergent,
      discriminant and construct validity of the instrument were assessed by classical
      test theory (CTT). The RSM was applied to investigate person and item
      reliability, item statistics and ordering of response categories. RESULTS: The
      CTT method showed that the scaling success rate for convergent and discriminant
      validity were 100% in all domains with the exception of physical health in the
      child self-report. Moreover, confirmatory factor analysis supported a four-factor
      model similar to its original version. The RSM showed that 22 out of 23 items had
      acceptable infit and outfit statistics (<1.4, >0.6), person reliabilities were
      low, item reliabilities were high, and item difficulty ranged from -1.01 to 0.71
      and -0.68 to 0.43 for child self-report and parent proxy-report, respectively.
      Also the RSM showed that successive response categories for all items were not
      located in the expected order. CONCLUSIONS: This study revealed that, in all
      domains, the five response categories did not perform adequately. It is not known
      whether this problem is a function of the meaning of the response choices in the
      Persian language or an artifact of a mostly healthy population that did not use
      the full range of the response categories. The response categories should be
      evaluated in further validation studies, especially in large samples of
      chronically ill patients.

PMID- 22414137
TI  - Biopolymer system for cell recovery from microfluidic cell capture devices.
AB  - Microfluidic systems for affinity-based cell isolation have emerged as a
      promising approach for the isolation of specific cells from complex matrices
      (i.e., circulating tumor cells in whole blood). However, these technologies
      remain limited by the lack of reliable methods for the innocuous recovery of
      surface captured cells. Here, we present a biofunctional sacrificial hydrogel
      coating for microfluidic chips that enables the highly efficient release of
      isolated cells (99% +/- 1%) following gel dissolution. This covalently cross
      linked alginate biopolymer system is stable in a wide variety of physiologic
      solutions (including EDTA treated whole blood) and may be rapidly degraded via
      backbone cleavage with alginate lyase. The capture and release of EpCAM
      expressing cancer cells using this approach was found to have no significant
      effect on cell viability or proliferative potential, and recovered cells were
      demonstrated to be compatible with downstream immunostaining and FISH analysis.

PMID- 22414138
TI  - Preliminary study of enteroscopy-guided, self-expandable metal stent placement
      for malignant small bowel obstruction.
AB  - BACKGROUND AND AIMS: Technical limitations of conventional endoscopes and
      delivery systems frequently hamper palliative endoscopic placement of self
      expandable metal stents for malignant small bowel obstruction. This study
      examined feasibility of the double balloon enteroscope-guided withdrawal
      reinsertion method as a rescue procedure in patients with failed palliative stent
      placement for malignant small bowel obstruction. METHODS: We enrolled 19
      consecutive patients with small bowel obstruction due to metastatic gastric (n =
      15) or colorectal cancer (n = 2), or primary small bowel carcinoma (n = 2), in
      whom previous attempts to place self-expandable metal stents using conventional
      endoscopy had failed. Ten patients had undergone previous gastric surgery. After
      passing a guide-wire using an enteroscope with or without the double-balloon
      method, the enteroscope was withdrawn. A conventional endoscope was re-inserted
      along the guide-wire, and through-the-scope self-expandable metal stent placement
      was performed. RESULTS: Obstruction sites were efferent jejunal loop, proximal
      jejunum, and third duodenal portion. Technical success was achieved with 94.7%
      (18/19) of stents, and clinical success occurred with 84.2% (16/19) of patients.
      The gastric outlet obstruction score (pre-procedure: 0.68 +/- 0.58) increased by
      one week (2.05 +/- 0.52, P < 0.001). Stent migration and restenosis occurred in
      two (10.5%) and four (21.1%) of 19 stents, respectively. Median stent patency
      duration was 67 days and median survival was 93 days; these did not differ
      significantly by palliative chemotherapy (P = 0.76 and 0.67, respectively).
      CONCLUSIONS: The double-balloon enteroscopy-guided method followed by
      conventional endoscopic self-expandable metal stent delivery was effective for
      rescue palliation of malignant small bowel obstruction.

PMID- 22414139
TI  - Guidelines for office gynecology in Japan: Japan Society of Obstetrics and
      Gynecology and Japan Association of Obstetricians and Gynecologists 2011 edition.
AB  - Gynecology in the office setting is developing worldwide. Clinical guidelines for
      office gynecology were first published by the Japan Society of Obstetrics and
      Gynecology and the Japan Association of Obstetricians and Gynecologists in 2011.
      These guidelines include a total of 72 clinical questions covering four areas
      (Infectious disease, Malignancies and benign tumors, Endocrinology and
      infertility, and Healthcare for women). These clinical questions were followed by
      several answers, backgrounds, explanations and references covering common
      problems and questions encountered in office gynecology. Each answer with a
      recommendation level of A, B or C has been prepared based principally on evidence
      or consensus among Japanese gynecologists.These guidelines would promote a better
      understanding of the current standard care practices for gynecologic outpatients
      in Japan.

PMID- 22414140
TI  - Details of the paranephridial system of a species of Prohyptiasmus
      (Cyclocoelidae: Hyptiasminae) from an American coot, Fulica americana (Rallidae)
      in Oklahoma.
AB  - During a study of the endohelminths of aquatic birds from the central flyway of
      North America, the details of the paranephridial systems of 3 immature specimens
      of Prohyptiasmus sp. were examined; the worms had been collected by the late Dr.
      J. Teague Self, former Professor, Department of Zoology, University of Oklahoma,
      Norman, Oklahoma from an American coot, Fulica americana (Raillidae), from the
      Cheyenne Bottoms, Roger Mills County, Oklahoma and deposited in the Harold W.
      Manter Laboratory of Parasitology. The excretory vesicle was Y-shaped and had a
      reduced stem. There were 3 main excretory canals on each side that, in the case
      of the most lateral 2 pairs, reached anteriorly to the level of the oral sucker.
      The most lateral canals entered the excretory vesicle about halfway down the stem
      on each side; the middle canals entered the vesicle at the tips of the branches
      of the vesicle; and the most medial canals entered the vesicle on the anterior
      edge about halfway between the branch point and the tips of the branches. There
      were numerous smaller secondary canals that interconnected with each other and
      with the 6 main paranephridial canals, forming a net-like system.

PMID- 22414141
TI  - Regional variation in the modeling of donation frequency: the case of Hema
      Quebec, Canada.
AB  - BACKGROUND: Many studies on factors that can affect the frequency of blood
      donation have shown the influence of several individual characteristics. However,
      few studies have analyzed regional variations in blood donation frequency. The
      objective of this article is to verify to what extent individual and geographic
      variables influence blood donation in the Province of Quebec, Canada. STUDY
      DESIGN AND METHODS: This article used a database provided by Hema-Quebec (the
      organization in charge of blood collection in Quebec), which included 426,247
      donors, who made 1.4 million donations over a period of 5 years. Using the
      donors' residential postal codes and those of the blood collection sites, we
      created two geographic variables: the distance between the donor's place of
      residence and his or her collection site and each donor's region of residence. We
      subsequently modeled the frequency of blood donation and the different donor
      categories (based on the number of blood donations) using both a negative
      binomial regression model and an ordinal logistic regression model. RESULTS: The
      results indicate that, once the individual characteristics have been taken into
      account, the geographic variables, including proximity to the collection site,
      have a significant impact on the frequency of blood donation. Likewise, according
      to the results of the negative binomial model, among the 17 regions in the
      Province of Quebec, there are five regions where blood donation incidence rate
      ratios (IRRs) are very high, that is, Abitibi-Temiscamingue (IRR, 1.77; 95%
      confidence interval [CI], 1.61-1.95); Bas-Saint-Laurent (IRR, 1.75; 95% CI, 1.59
      1.93); Saguenay-Lac-Saint-Jean (IRR, 1.68; 95% CI, 1.53-1.84); Centre-du-Quebec
      (IRR, 1.66; 95% CI, 1.51-1.83); and Chaudiere-Appalaches (IRR, 1.62; 95% CI, 1.48
      1.78). CONCLUSION: Such knowledge of the geography of blood donations makes it
      possible to better target certain regions when planning new blood drives, to
      ensure a constant blood supply.

PMID- 22414142
TI  - Trends in the prevalence of thrombocytopenia among individuals infected with
      hepatitis C virus in the United States, 1999-2008.
AB  - BACKGROUND: Thrombocytopenia is associated with the natural history of hepatitis
      C virus (HCV) infection and anti-viral therapy. Recent, national estimates of the
      clinical burden of thrombocytopenia among HCV-infected individuals in the United
      States are unavailable. Bi-yearly data from the 1999-2000 to 2007-2008 National
      Health and Nutrition Examination Surveys (NHANES) were used to examine the
      prevalence of thrombocytopenia among HCV-infected individuals in the United
      States. RESULTS: Among 467 HCV-infected individuals in the survey (weighted
      population = 3,597,039), mean weighted age was 46.7 years (standard deviation =
      15.5) and 61.7% were male. Overall, 7.6% met the study definition of TCP at the
      150 * 10(9)/L threshold; 4.5%, 2.0%, and 0.8% had platelet counts below 125, 100,
      and 75 * 10(9)/L, respectively. The 2-year weighted prevalences of
      thrombocytopenia (150 * 10(9)/L threshold) from 1999-2008 were 4.9%, 8.6%, 6.5%,
      4.1%, and 12.9%. The unadjusted biannual time trend (odds ratio) was 1.16 (95%
      confidence interval = 0.82-1.64). In the two adjusted models, the odds by time
      ranged from 1.24-1.40, depending on whether the model included demographic or
      laboratory variables or both, but did not reach statistical significance. Age was
      positively and significantly related to thrombocytopenia status. CONCLUSIONS: As
      the HCV-infected population ages, the prevalence of thrombocytopenia is expected
      to rise. This study provides limited evidence of such an effect at the national
      level.

PMID- 22414143
TI  - Active head lifting from supine in infancy: a significant stereotypy?

PMID- 22414144
TI  - Chinese students in Japan: the mediator and the moderator between their
      personality and mental health.
AB  - To clarify the influence of personality traits on the psychological acculturation
      of Chinese international students in Japan, the present study used three
      structuring questions: (a) What personality trait makes the students vulnerable
      to psychological distress? (b) What mediates between personality and
      psychological distress? (c) What buffers personality from psychological distress?
      The study examined personality traits (Harm-Avoidance, HA; and Self-Directedness,
      SD; two dimensions of the Temperament and Character Inventory), acculturation
      attitudes (integration, assimilation, separation, and marginalization), and the
      mental health (General Health Questionnaire (GHQ)-30) of 253 Chinese students in
      Japan (17-30 years of age) using self-report questionnaires. The hypotheses are:
      For the Chinese international students in Japan, (a) the individuals with high HA
      or low SD are more vulnerable to psychological distress; (b) the acculturation
      strategy mediates between personality (HA/SD) and mental health (GHQ); (c) social
      support can moderate the effect of personality on acculturation adaptation. The
      results show that the Chinese international students in Japan had higher GHQ
      scores compared to normative standards, and marginalization (a less adaptive
      strategy) was their second most preferred acculturation strategy, next to
      integration. Individuals with high HA or low SD were more likely to have a
      marginalization attitude and suffer from more psychological distress. The
      mediation effect of marginalization and the moderation effect of social support
      in life (SSL) between HA/SD and GHQ were confirmed. Most of the hypotheses were
      supported by the results. Explanations of these findings and their implication
      for acculturation adaptation are discussed. 

PMID- 22414145
TI  - TLR4, IL-6, IL-18, MyD88 and HMGB1 are highly expressed in intracranial
      inflammatory lesions and the IgG4/IgG ratio correlates with TLR4 and IL-6.
AB  - We determined distribution of plasma cells and IgG4/IgG index and factors
      associated with the index in intracranial inflammatory lesions. Specimens of nine
      patients were analyzed immunohistochemically using antibodies against CD45, CD68,
      CD3, CD4, CD8, CD20, CD138, lambda chain, kappa chain, IgG, IgG4, IL-1alpha, IL
      6, IL-18, toll-like receptor (TLR) 2, TLR4, high-mobility group box 1 (HMGB1),
      tumor necrosis factor-alpha (TNF-alpha), myeloid differentiation factor 88
      (MyD88), and anaplastic lymphoma kinase (ALK). The relationship between all the
      factors was assessed using Spearman's rank correlation coefficient (rho).
      Negative ALK staining was observed in all the patients. Plasma cells were
      detected in eight patients with varying degrees. The highest number of
      neutrophils, but no plasma cells, was observed in a patient with the shortest
      history of inflammation. IgG4/IgG index was independent of the number of plasma
      cells. The index was relatively highly correlated with IL-6 (rho = 0.7271) and
      TLR4 expression (rho = 0.7246). IL-6 expression was highly correlated with TLR4
      expression (rho = 0.8042). IL-18 was maximally expressed in all the patients.
      TLR4 expression was strong, but TRL2 expression was weak. Positive HMGB1 staining
      was observed in all the patients, predominantly in the nuclei, but also in the
      cytoplasm in four patients. The cytoplasmic expression strongly correlated with
      IL-1alpha expression (rho = 0.9583). The cytoplasmic colocalization of HMGB1 and
      IL-1alpha was histologically confirmed in cells with collapsing nuclei by the
      double-staining method. The IgG4/IgG indexes varied case by case. IL-6 and TLR4
      expressions may influence IgG4/IgG index. The nuclei of cells with both IL-1alpha
      and HMGB1 expressions in the cytoplasm collapse in the cell death stage. The
      cooperative high expression of TLR4, IL-6, IL-18, MyD88 and HMGB1 suggest their
      critical roles in the inflammation circuit.

PMID- 22414146
TI  - Two-dimensional nanomembranes: can they outperform lower dimensional
      nanocrystals?
AB  - Inorganic nanomembranes, analogues to graphene, are expected to impact a wide
      range of device concepts including thin-film or flexible platforms. Size
      dependent properties and high surface area-two key characteristics of zero- (0D)
      and one-dimensional (1D) nanocrystals-are still present in most nanomembranes,
      rendering their use more probable in practical applications. These advantages
      make nanomembranes strong contenders for outpacing 0D and 1D nanocrystals, which
      are often difficult to integrate into commercial device technologies. This
      Perspective highlights important progress made by Wang et al. (doi:
      10.1021/nn2050906) in large-scale fabrication of free-standing nanomembranes by
      using a solution-based technique, as reported in this issue of ACS Nano. The
      simplicity of this new approach and the elimination of typical delamination
      processes used in top-down nanomembrane fabrications are among the strengths of
      this technique. Areas for improvement along with an overview of other related
      work are also discussed.

PMID- 22414147
TI  - Antimicrobial efficacy of alcohol-based hand gels with a 30-s application.
AB  - AIMS: The objective of this study was to assess the antimicrobial efficacy of
      alcohol-based hand gels according to European Norm 1500 (EN 1500). METHODS AND
      RESULTS: We assessed the antimicrobial efficacy of 12 alcohol-based hand gels
      produced in Brazil, containing 70% w/w or v/v ethyl alcohol as the active
      ingredient, according to EN 1500, with a 30-s application. In addition, 70% w/w
      ethyl alcohol and three alcohol-based hand rubs commonly used in Europe and
      effective according to EN 1500 were also tested. Eight of 12 (67%) alcohol-based
      hand gels produced in Brazil failed by EN 1500. In contrast, 70% w/w ethyl
      alcohol and European alcohol-based hand rubs were approved by EN 1500.
      CONCLUSIONS: In this study, the majority of Brazilian alcohol-based hand gels
      showed limited efficacy on hand hygiene within 30 s. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The findings of this study may be used as an important argument to
      motivate Brazilian manufacturers to improve the antimicrobial efficacy of alcohol
      based hand gels, because it is prudent to suppose that alcohol-based hand gels
      can be recommended for use in healthcare settings only if they show antimicrobial
      activity at least similar to that of alcohol-based liquid preparations, including
      the traditional 70% w/w ethyl alcohol.

PMID- 22414148
TI  - Generation of functional coatings on hydrophobic surfaces through deposition of
      denatured proteins followed by grafting from polymerization.
AB  - Hydrophilic coatings were produced on flat hydrophobic substrates featuring n
      octadecyltrichlorosilane (ODTS) and synthetic polypropylene (PP) nonwoven
      surfaces through the adsorption of denatured proteins. Specifically,
      physisorption from aqueous solutions of alpha-lactalbumin, lysozyme, fibrinogen,
      and two soy globulin proteins (glycinin and beta-conglycinin) after chemical
      (urea) and thermal denaturation endowed the hydrophobic surfaces with amino and
      hydroxyl functionalities, yielding enhanced wettability. Proteins adsorbed
      strongly onto ODTS and PP through nonspecific interactions. The thickness of
      adsorbed heat-denatured proteins was adjusted by varying the pH, protein
      concentration in solution, and adsorption time. In addition, the stability of the
      immobilized protein layer was improved significantly after interfacial cross
      linking with glutaraldehyde in the presence of sodium borohydride. The amino and
      hydroxyl groups present on the protein-modified surfaces served as reactive sites
      for the attachment of polymerization initiators from which polymer brushes were
      grown by surface-initiated atom-transfer radical polymerization of 2-hydroxyethyl
      methacrylate. Protein denaturation and adsorption as well as the grafting of
      polymeric brushes were characterized by circular dichroism, ellipsometry, contact
      angle, and Fourier transform infrared spectroscopy in the attenuated total
      reflection mode.

PMID- 22414149
TI  - Effect of adsorption and regeneration temperature on irreversible adsorption of
      organic vapors on beaded activated carbon.
AB  - This paper investigates the effect of adsorption and regeneration temperature on
      the irreversible adsorption of a mixture of organic compounds typically emitted
      from automobile painting operations. Adsorption of the organic vapors mixture
      onto microporous beaded activated carbon (BAC) and regeneration of the saturated
      BAC were completed under different conditions. Results indicated that increasing
      the adsorption temperature from 25 to 35 or 45  degrees C increased heel buildup
      on BAC by about 30% irrespective of the regeneration temperature due to
      chemisorption. The adsorption capacity (for the first cycle) of the mixture onto
      the BAC at these three temperatures remained almost unchanged indicating
      chemisorption of some of these compounds onto the BAC. Increasing the
      regeneration temperature from 288 to 400  degrees C resulted in 61% reduction in
      the heel at all adsorption temperatures, possibly due to desorption of chemicals
      from narrow micropores. BET area and pore volumes of the BAC decreased
      proportionally to the cumulative heel. Pore size distribution and pore volume
      reduction confirmed that the heel was mainly built up in narrow micropores which
      can be occupied or blocked by some of the adsorbates.

PMID- 22414150
TI  - Nickel-catalyzed Negishi alkylations of styrenyl aziridines.
AB  - A nickel-catalyzed cross-coupling reaction between N-sulfonyl aziridines and
      organozinc reagents is reported. The catalytic system comprises an inexpensive
      and air-stable Ni(II) source and dimethyl fumarate as ligand. Regioselective
      synthesis of beta-substituted amines is possible under mild and functional-group
      tolerant conditions. The stereoselectivity of the reaction is consistent with a
      stereoconvergent mechanism wherein the sulfonamide directs C-C bond formation.

PMID- 22414151
TI  - Expert commentary. Teaching case: New onset migraine with aura?

PMID- 22414152
TI  - Feature detection with controlled error rates in LC/MS images.
AB  - The Median M-N rule is a feature detection algorithm to detect peptide signals in
      Liquid Chromatography/Mass Spectrometry (LC/MS) images. As the procedure does not
      adequately control the statistical errors, we investigate an extension of the
      Median M-N rule to compute a statistical bound on the false-positive rate. We
      then study the false-negative rate and provide insights on the types of signal
      that can be detected by the M-N rule and the limit of detection. The resulting
      feature detection algorithm, which we term Quantile M-N rule, can be used in most
      feature detection algorithms to provide statistical control of the false-positive
      and false-negative rate.

PMID- 22414153
TI  - Improved harmonic mean estimator for phylogenetic model evidence.
AB  - Bayesian phylogenetic methods are generating noticeable enthusiasm in the field
      of molecular systematics. Many phylogenetic models are often at stake, and
      different approaches are used to compare them within a Bayesian framework. The
      Bayes factor, defined as the ratio of the marginal likelihoods of two competing
      models, plays a key role in Bayesian model selection. We focus on an alternative
      estimator of the marginal likelihood whose computation is still a challenging
      problem. Several computational solutions have been proposed, none of which can be
      considered outperforming the others simultaneously in terms of simplicity of
      implementation, computational burden and precision of the estimates.
      Practitioners and researchers, often led by available software, have privileged
      so far the simplicity of the harmonic mean (HM) estimator. However, it is known
      that the resulting estimates of the Bayesian evidence in favor of one model are
      biased and often inaccurate, up to having an infinite variance so that the
      reliability of the corresponding conclusions is doubtful. We consider possible
      improvements of the generalized harmonic mean (GHM) idea that recycle Markov
      Chain Monte Carlo (MCMC) simulations from the posterior, share the computational
      simplicity of the original HM estimator, but, unlike it, overcome the infinite
      variance issue. We show reliability and comparative performance of the improved
      harmonic mean estimators comparing them to approximation techniques relying on
      improved variants of the thermodynamic integration.

PMID- 22414154
TI  - Accurate mass spectrometry based protein quantification via shared peptides.
AB  - In mass spectrometry-based protein quantification, peptides that are shared
      across different protein sequences are often discarded as being uninformative
      with respect to each of the parent proteins. We investigate the use of shared
      peptides which are ubiquitous (~50% of peptides) in mass spectrometric data-sets
      for accurate protein identification and quantification. Different from existing
      approaches, we show how shared peptides can help compute the relative amounts of
      the proteins that contain them. Also, proteins with no unique peptide in the
      sample can still be analyzed for relative abundance. Our article uses shared
      peptides in protein quantification and makes use of combinatorial optimization to
      reduce the error in relative abundance measurements. We describe the topological
      and numerical properties required for robust estimates, and use them to improve
      our estimates for ill-conditioned systems. Extensive simulations validate our
      approach even in the presence of experimental error. We apply our method to a
      model of Arabidopsis thaliana root knot nematode infection, and investigate the
      differential role of several protein family members in mediating host response to
      the pathogen.

PMID- 22414155
TI  - Differential solubility of ethylene and acetylene in room-temperature ionic
      liquids: a theoretical study.
AB  - The room-temperature ionic liquids (RTILs) have potential in realizing the
      ethylene (C(2)H(4)) and acetylene (C(2)H(2)) separation and avoiding solvent loss
      and environmental pollution compared with traditional solvents. The interaction
      mechanisms between gases and RTILs are important for the exploration of new RTILs
      for gas separation; thus, they were studied by quantum chemical calculation and
      molecular dynamics simulation in this work. The optimized geometries were
      obtained for the complexes of C(2)H(4)/C(2)H(2) with anions (Tf(2)N(-), BF(4)(-),
      and OAc(-)), cation (bmim(+)), and their ion pairs, and the analysis for
      geometry, interaction energy, natural bond orbital (NBO), and atoms in molecules
      (AIM) was performed. The quantum chemical calculation results show that the
      hydrogen-bonding interaction between the gas molecule and anion is the dominant
      factor in determining the solubility of C(2)H(2) in RTILs. However, the hydrogen
      bonding interaction, the p-pi interaction in C(2)H(4)-anion, and the pi-pi
      interaction in C(2)H(4)-cation are weak and comparable, which all affect the
      solubility of C(2)H(4) in RTILs with comparable contribution. The calculated
      results for the distance of H(gas)...X (X = O or F in anions), the BSSE-corrected
      interaction energy, the electron density of H(gas)...X at the bond critical point
      (rho(BCP)), and the relative second-order perturbation stabilization energy
      (E(2)) are consistent with the experimental data that C(2)H(2) is more soluble
      than C(2)H(4) in the same RTILs and the solubility of C(2)H(4) in RTILs has the
      following order: [bmim][Tf(2)N] > [bmim][OAc] > [bmim][BF(4)]. The calculated
      results also agree with the order of C(2)H(2) solubility in different RTILs that
      [bmim][OAc] > [bmim][BF(4)] > [bmim][Tf(2)N]. Furthermore, the calculation
      results indicate that there is strong C(2)H(2)-RTIL interaction, which cannot be
      negligible compared to the RTIL-RTIL interaction; thus, the regular solution
      theory is probably not suitable to correlate C(2)H(2) solubility in RTILs. The
      molecular dynamics simulation results show that the hydrogen bond between the H
      in C2 of the imidazolium cation and the anion will weaken the hydrogen-bonding
      interaction of the gas molecule and anion in a realistic solution condition,
      especially in the C(2)H(4)-RTIL system.

PMID- 22414158
TI  - High-definition X-ray fluorescence elemental mapping of paintings.
AB  - A historical self-portrait painted by Sir Arthur Streeton (1867-1943) has been
      studied with fast-scanning X-ray fluorescence microscopy using synchrotron
      radiation. One of the technique's unique strengths is the ability to reveal metal
      distributions in the pigments of underlying brushstrokes, thus providing
      information critical to the interpretation of a painting. We have applied the
      nondestructive technique with the event-mode Maia X-ray detector, which has the
      capability to record elemental maps at megapixels per hour with the full X-ray
      fluorescence spectrum collected per pixel. The painting poses a difficult
      challenge to conventional X-ray analysis, because it was completely obscured with
      heavy brushstrokes of highly X-ray absorptive lead white paint
      (2PbCO(3).Pb(OH)(2)) by the artist, making it an excellent candidate for the
      application of the synchrotron-based technique. The 25 megapixel elemental maps
      were successfully observed through the lead white paint across the 200 * 300
      mm(2) scan area. The sweeping brushstrokes of the lead white overpaint
      contributed significant detrimental structure to the elemental maps. A corrective
      procedure was devised to enhance the visualization of the elemental maps by using
      the elastic X-ray scatter as a proxy for the lead white overpaint. We foresee the
      technique applied to the most demanding of culturally significant artworks where
      conventional analytical methods are inadequate.

PMID- 22414157
TI  - A prospective clinical trial on the influence of a triamcinolone/demeclocycline
      and a calcium hydroxide based temporary cement on pain perception.
AB  - INTRODUCTION: The aim of this clinical trial was to compare the degree of short
      term post-operative irritation after application of a
      triamcinolone/demeclocycyline based or a calcium hydroxide based provisional
      cement. METHODS: A total of 109 patients (55 female and 54 male; mean age: 51 +/-
      14 years) with primary or secondary dentinal caries were randomly assigned to the
      two treatment groups of this biomedical clinical trial (phase III). Selection
      criteria were good systemic health and treated teeth, which were vital and showed
      no symptoms of pulpitis. Up to three teeth were prepared for indirect metallic
      restorations, and the provisional restorations were cemented with a
      triamcinolone/demeclocycyline (Ledermix) or a calcium hydroxide (Provicol) based
      material. The intensity of post-operative pain experienced was documented
      according to the VAS (4, 12, 20, 24, and 82 h) and compared to VAS baseline.
      RESULTS: A total of 159 teeth were treated (Ledermix: 83 teeth, Provicol: 76
      teeth). The minor irritation of the teeth, experienced prior to treatment, was
      similar in both groups; however, 4 h after treatment this value was significantly
      higher in the Provicol group than in the Ledermix group (p < 0.005, t-test).
      After 12 h, the difference was no longer significant. The number of patients
      taking analgesics for post-treatment pain was higher in the Provicol group (n =
      11/53) than in the Ledermix group (n = 3/56). CONCLUSIONS: The patients had no
      long term post-operative pain experience in both groups. However, within the
      first hours after cementation the sensation of pain was considerably higher in
      the Provicol group than in the Ledermix group.

PMID- 22414156
TI  - IL-1RI (interleukin-1 receptor type I) signalling is essential for host defence
      and hemichannel activity during acute central nervous system bacterial infection.
AB  - Staphylococcus aureus is a common aetiological agent of bacterial brain
      abscesses. We have previously established that a considerable IL-1 (interleukin
      1) response is elicited immediately following S. aureus infection, where the
      cytokine can exert pleiotropic effects on glial activation and blood-brain
      barrier permeability. To assess the combined actions of IL-1alpha and IL-1beta
      during CNS (central nervous system) infection, host defence responses were
      evaluated in IL-1RI (IL-1 receptor type I) KO (knockout) animals. IL-1RI KO mice
      were exquisitely sensitive to intracerebral S. aureus infection, as demonstrated
      by enhanced mortality rates and bacterial burdens within the first 24 h following
      pathogen exposure compared with WT (wild-type) animals. Loss of IL-1RI signalling
      also dampened the expression of select cytokines and chemokines, concomitant with
      significant reductions in neutrophil and macrophage infiltrates into the brain.
      In addition, the opening of astrocyte hemichannels during acute infection was
      shown to be dependent on IL-1RI activity. Collectively, these results demonstrate
      that IL-1RI signalling plays a pivotal role in the genesis of immune responses
      during the acute stage of brain abscess development through S. aureus
      containment, inflammatory mediator production, peripheral immune cell
      recruitment, and regulation of astrocyte hemichannel activity. Taken in the
      context of previous studies with MyD88 (myeloid differentiation primary response
      gene 88) and TLR2 (Toll-like receptor 2) KO animals, the current report advances
      our understanding of MyD88-dependent cascades and implicates IL-1RI signalling as
      a major antimicrobial effector pathway during acute brain-abscess formation.

PMID- 22414159
TI  - Characterization of chromosome-specific genomic DNA from hexaploid oat.
AB  - We have sequenced, assembled, and characterized a set of complexity-reduced
      genomic clones derived from a chromosome 18D-specific library from hexaploid oat
      ( Avena sativa  L.). Sequences from 314 clones were assembled into 99 contigs of
      identical or nearly identical sequence. The Censor tool was used to identify
      similarity to known and characterized repeat sequences in RepBase. Eight repeat
      classes were scattered throughout 50 contigs, with most repeats belonging to
      seven transposon and retrotransposon classes. After accounting for known repeats,
      additional matches to orthologous genes from other species were identified in 24
      regions of 22 contigs, and an additional 47 regions matched genomic sequences
      from oat and other related species. These results provide information about the
      types and density of transposable elements in the oat genome, as well as the
      potential for identifying unique or chromosome-specific sequence elements in oat.
      Overall, these results predict a low success rate in identifying chromosome
      specific coding regions in oat through chromosome isolation and genome complexity
      reduction.

PMID- 22414160
TI  - Structure and mechanism of diet specialisation: testing models of individual
      variation in resource use with sea otters.
AB  - Studies of consumer-resource interactions suggest that individual diet
      specialisation is empirically widespread and theoretically important to the
      organisation and dynamics of populations and communities. We used weighted
      networks to analyze the resource use by sea otters, testing three alternative
      models for how individual diet specialisation may arise. As expected, individual
      specialisation was absent when otter density was low, but increased at high-otter
      density. A high-density emergence of nested resource-use networks was consistent
      with the model assuming individuals share preference ranks. However, a density
      dependent emergence of a non-nested modular network for 'core' resources was more
      consistent with the 'competitive refuge' model. Individuals from different diet
      modules showed predictable variation in rank-order prey preferences and handling
      times of core resources, further supporting the competitive refuge model. Our
      findings support a hierarchical organisation of diet specialisation and suggest
      individual use of core and marginal resources may be driven by different
      selective pressures.

PMID- 22414161
TI  - Carbon-boron bond cross-coupling reaction catalyzed by -PPh(2) containing
      palladium-indolylphosphine complexes.
AB  - This study describes the application of indolylphosphine ligands with a
      diphenylphosphino moiety to the palladium-catalyzed borylation of aryl chlorides.
      The combination of palladium metal precursor with PPh(2)-Andole-phos, which
      comprises an inexpensive -PPh(2) group, provides highly effective catalysts for
      the borylation of aryl chlorides. A range of functional groups such as -CN, 
      NO(2), -CHO, -COMe, -COOMe, and -CF(3) was compatible, and the catalyst loading
      down to 0.025 mol % of Pd can be achieved. The Pd/PPh(2)-Andole-phos system is
      able to catalyze both borylation reaction and Suzuki-Miyaura coupling reaction in
      a one-pot sequential manner for the direct synthesis of biaryl compounds in
      excellent yields.

PMID- 22414162
TI  - Prevalence and associated factors with esophageal varices in early primary
      biliary cirrhosis.
AB  - BACKGROUND AND AIMS: Recent routine testing for anti-mitochondrial antibodies has
      increased the number of patients with early primary biliary cirrhosis (PBC). The
      prevalence and clinical significance of esophageal varices in those patients
      remains obscure. METHODS: A systematic cohort analysis of 256 PBC patients was
      performed to clarify the prevalence, characteristics, and prognosis of the
      patients with early PBC and esophageal varices. RESULTS: Twenty-two patients had
      esophageal varices at the time of diagnosis: 5.5% (12/217) with early disease of
      histological stage 1 or 2, and 25.6% (10/39) with advanced disease of stage 3 or
      4. Immediate treatments were required for two patients with early PBC: one for
      bleeding varices, and the other for large varices. The overall survival of the
      patients with early PBC and esophageal varices at diagnosis did not significantly
      differ from that of patients without esophageal varices (P = 0.66). High alkaline
      phosphatase (ALP) ratios (odds ratio = 2.3) and low platelet counts (odds ratio =
      0.77) were significantly associated with the presence of esophageal varices in
      the patients with early PBC. Significant associations of these two factors with
      the development of esophageal varices during follow-up were also revealed (odds
      ratio = 1.4 and 0.88, respectively). The patients with early PBC and high ALP
      ratios >= 1.9 had significantly high risks of developing esophageal varices
      during follow-up (P = 0.022). CONCLUSIONS: High ALP ratios and low platelet
      counts at diagnosis and decreased platelet counts during follow-up are useful
      predictors of esophageal varices in patients with early PBC.

PMID- 22414163
TI  - Long-term beneficial effect of protease inhibitors on the intrinsic apoptosis of
      peripheral blood mononuclear cells in HIV-infected patients.
AB  - BACKGROUND: Viral suppression by antiretroviral therapy (ART) inhibits HIV
      induced apoptosis and CD4 T-cell loss. It has been suggested that protease
      inhibitors (PIs) have nonviral antiapoptotic effects by maintaining mitochondrial
      integrity. Long-term clinical effects of PI-based ART on mitochondrial toxicity
      and lymphocyte apoptosis beyond viral suppression have not been exploited to
      date. METHODS: We conducted a 7-year study on HIV-1-infected patients from the
      Cologne HIV cohort with sufficient viral suppression under either a PI-based or
      nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. Eight
      patients on PI and eight on NNRTI were eligible for inclusion in the analysis.
      The primary outcome measure was defined as a change in the mitochondrial-to
      nuclear DNA ratio in PBMCs. Further key molecules involved in extrinsic [tumour
      necrosis factor-related apoptosis-inducing ligand (TRAIL), Fas ligand (FasL) and
      caspase 8], intrinsic [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein
      (Bax), caspase 9 and lactate-to-pyruvate ratio] and overall apoptosis [Annexin+/7
      aminoactinomycin D (7-AAD)- and caspase 3/7] and viral activity [negative
      regulatory factor (Nef), interferon-alpha (IFN-alpha) and myxovirus resistance
      protein A (MxA)] were measured. RESULTS: Demographic and baseline clinical
      parameters were similar in the two groups, except that patients in the PI group
      had a higher mean age. After 7 years of treatment, CD4 T-cell count increased and
      the expression of genes encoding the proapoptotic viral protein Nef and HIV
      induced cytokine IFN-alpha and its downstream effector MxA decreased in both
      groups. Focusing on the different pathways of apoptosis, only in the PI group
      intrinsic apoptosis decreased significant and in the inter-group comparison the
      decrease was significantly higher than in the NNRTI group. CONCLUSIONS: Our study
      provides evidence that long-term therapy with a PI-based regimen may be superior
      to that with a NNRTI-based regimen with regard to its intrinsic antiapoptotic
      effect.

PMID- 22414165
TI  - Prevalence of pulmonary TB and spoligotype pattern of Mycobacterium tuberculosis
      among TB suspects in a rural community in Southwest Ethiopia.
AB  - BACKGROUND: In Ethiopia where there is no strong surveillance system and state of
      the art diagnostic facilities are limited, the real burden of tuberculosis (TB)
      is not well known. We conducted a community based survey to estimate the
      prevalence of pulmonary TB and spoligotype pattern of the Mycobacterium
      tuberculosis isolates in Southwest Ethiopia. METHODS: A total of 30040 adults in
      10882 households were screened for pulmonary TB in Gilgel Gibe field research
      centre in Southwest Ethiopia. A total of 482 TB suspects were identified and
      smear microscopy and culture was done for 428 TB suspects. Counseling and testing
      for HIV/AIDS was done for all TB suspects. Spoligotyping was done to characterize
      the Mycobacterium tuberculosis isolates. RESULTS: Majority of the TB suspects
      were females (60.7%) and non-literates (83.6%). Using smear microscopy, a total
      of 5 new and 4 old cases of pulmonary TB cases were identified making the
      prevalence of TB 30 per 100,000. However, using the culture method, we identified
      17 new cases with a prevalence of 76.1 per 100,000. There were 4.3 undiagnosed
      pulmonary TB cases for every TB case who was diagnosed through the passive case
      detection mechanism in the health facility. Eleven isolates (64.7%) belonged to
      the six previously known spoligotypes: T, Haarlem and Central-Asian (CAS). Six
      new spoligotype patterns of Mycobacterium tuberculosis, not present in the
      international database (SpolDB4) were identified. None of the rural residents was
      HIV infected and only 5 (5.5%) of the urban TB suspects were positive for HIV.
      CONCLUSION: The prevalence of TB in the rural community of Southwest Ethiopia is
      low. There are large numbers of undiagnosed TB cases in the community. However,
      the number of sputum smear-positive cases was very low and therefore the risk of
      transmitting the infection to others may be limited. Active case finding through
      health extension workers in the community can improve the low case detection rate
      in Ethiopia. A large scale study on the genotyping of Mycobacterium tuberculosis
      in Ethiopia is crucial to understand transmission dynamics, identification of
      drug resistant strains and design preventive strategies.

PMID- 22414166
TI  - Detection of antibodies in wild ruminants to evaluate exposure to liver
      trematodes.
AB  - Wild ruminants sharing pastures with domestic livestock are at risk of infection
      by liver trematodes. Detection of antibodies provides a very useful tool to gain
      more knowledge about the distribution of these parasites. Non-lethal methods are
      strongly encouraged for the analysis of the risk of infection among wild
      ruminants. A seroepidemiological survey was conducted to analyze exposure to
      hepatic trematodes ( Fasciola hepatica and Dicrocoelium dendriticum ) in wild
      ruminants from southern Spain. Blood samples were collected from 69 bovids
      (Mouflon + Spanish ibex) and 143 cervids (red deer + fallow deer) from Sierra de
      Cazorla, Segura and Las Villas Natural Park. The samples were analyzed using the
      excretory/secretory antigens of each trematode to determine the IgG response. All
      the animals were examined at necropsy for the presence of flukes, and the
      species, age, and gender of the animals were recorded. Fasciola hepatica were
      only observed in cervids (3%; 95% confidence interval [CI]  =  2-8), while D.
      dendriticum specimens were recorded in 1% (0-8) of bovids and 4% (CI  =  2-9) of
      the cervids. The IgG-seroprevalence against F. hepatica was significantly higher
      in the cervids. Statistical differences according to gender were observed. The
      bovids exhibited the greatest percentages of positive cases to D. dendriticum
      antigens, and the DdES-seroprevalence was related to age of the animals. When
      considering all the factors, the FhES-seroprevalence was initially distributed
      according to the type of ruminant (cervids), gender (male), and age (>2 yr).

PMID- 22414167
TI  - Comparison of cystatin C- and creatinine-based estimation of glomerular
      filtration rate according to glycaemic status in Type 2 diabetes.
AB  - AIMS: The influence of hyperglycaemia on the performance of glomerular filtration
      rate (GFR) estimating equations remains to be determined. We compared the
      performance of creatinine-based GFR with cystatin C-based GFR in patients with
      Type 2 diabetes according to glycaemic status. METHODS: In a cross-sectional
      study of 210 patients with Type 2 diabetes, we staged glycaemic status by HbA(1c)
      tertiles [HbA(1c) <= 75 mmol/mol (9.0%) (n = 70), HbA(1c) 76-95 mmol/mol (9.1
      10.8%) (n = 70), HbA(1c) >95 mmol/mol (10.8%) (n = 70)] and measured GFR.
      Isotopic GFR was measured using renal dynamic imaging with (99m) Tc-diethylene
      triamine-penta-acetic acid. Estimated GFR (eGFR) was measured using creatinine
      based formulae (Cockcroft-Gault-eGFR, the Modification of Diet in Renal Disease
      equation-eGFR and the Chronic Kidney Disease Epidemiology Collaboration formula
      eGFR) and a cystatin C-based formula (cystatin C-eGFR). RESULTS: The isotopic GFR
      of all patients was 93.1 +/- 34.1 ml min(-1) 1.73 m(-2). All methods for
      estimating GFR underestimated isotopic GFR [Cockcroft-Gault-eGFR (68.8 +/- 38.6
      ml min(-1) 1.73 m(-2) ) (P < 0.05), Modification of Diet in Renal Disease-eGFR
      (74.8 +/- 31.3 ml min(-1) 1.73 m(-2) ) (P < 0.05), Chronic Kidney Disease
      Epidemiology Collaboration-eGFR (72.9 +/- 26.6 ml min(-1) 1.73 m(-2)) (P < 0.05)
      and cystatin C-eGFR (83.5 +/- 33.2 ml min(-1) 1.73 m(-2)) (P < 0.05)]. In all
      patient groups, cystatin C-eGFR was less biased and more accurate than the
      creatinine-based formulae, especially in the group with HbA(1c) > 95 mmol/mol
      (10.8%) where there was no difference between cystatin C-eGFR and isotopic GFR.
      CONCLUSIONS: Performance of cystatin C-eGFR was superior to creatinine-based GFR
      in patients with Type 2 diabetes with HbA(1c) >95 mmol/mol (10.8%).

PMID- 22414168
TI  - Staging of lung cancer in a tertiary care setting in Sri Lanka, using TNM 7th
      edition. A comparison against TNM6.
AB  - BACKGROUND: Lung cancer is a leading cause of cancer-related mortality in Sri
      Lanka and throughout the world. The latest staging system for lung cancer is the
      tumor node metastasis (TNM) 7th edition in which there are major changes to the
      previous version. The objective of our study was to find out the implications of
      TNM7th edition on lung cancer staging in a resource limited setting, and to
      compare it with the previous TNM 6th edition. METHODS: Patients with
      histologically proven lung cancer consecutively presented to respiratory unit of
      Teaching Hospital Kandy, Sri Lanka were recruited to the study over a period of
      one year from April 2010 to March 2011. They were staged using CT, ultrasound
      scan of abdomen, bronchoscopy and CT spine and brain when necessary. Staging was
      done using TNM 7 as well as TNM6. Surgical or non-surgical treatment arms were
      decided on staging and the number of patients in each treatment arm was compared
      between the two staging systems. RESULTS: Out of 62 patients, thirty four
      patients (54%) had metastatic disease and 19 (30%) of them had pleural effusions
      (M1a), while 15 (24%) had distant metastasis (M1b). When compared to TNM6 there
      was no difference in the number of patients in T1 category, but the number in T2
      was higher in TNM7 (25 Vs 20). Similarly the number in T3 group was higher in
      TNM7 (11 Vs 5) and the number in M category was doubled (34 Vs 17 [Chi-6.46, p =
      0.011]) compared to TNM 6. The number of patients suitable for surgery were
      17(27.5%) in TNM 7 and 18(29%) [Chi-0.02, p = 0.88] in TNM6. CONCLUSIONS: This
      study shows that a significant proportion of patients were having advanced
      disease with distant metastasis on presentation. The number of patients falling
      to stage IV is significantly higher when staged with TNM7 but there was no
      significant difference in the number of patients undergoing surgery when TNM 7
      was used compared to TNM6.

PMID- 22414169
TI  - Stable performance of non-aerated two-stage partial nitritation/anammox (PANAM)
      with minimal process control.
AB  - Partial nitritation/anammox (PANAM) technologies have rapidly developed over the
      last decade, but still considerable amounts of energy are required for active
      aeration. In this study, a non-aerated two-stage PANAM process was investigated.
      In the first-stage upflow fixed-film bioreactor, nitratation could not be
      prevented at ammonium loading rates up to 186 mg N l(-1) d(-1) and low influent
      dissolved oxygen (0.1 mg O(2) l(-1)). Yet, increasing the loading rate to 416 and
      747 mg N l(-1) d(-1) by decreasing the hydraulic retention time to 8 and 5 h,
      respectively, resulted in partial nitritation with the desired nitrite to
      ammonium nitrogen ratio for the subsequent anammox stage (0.71-1.05). The second
      stage anammox reactor was established with a synthetic feeding based on ammonium
      and nitrite. After establishing anammox at low biomass content (0.5 g VSS l(-1)),
      the anammox influent was switched to partial nitritation effluent at a loading
      rate of 71 mg N l(-1) d(-1), of which 78% was removed at the stoichiometrically
      expected nitrite to ammonium consumption ratios (1.19) and nitrate production to
      ammonium consumption ratio (0.24). The combined PANAM reactors were operated for
      3 months at a stable performance. Overall, PANAM appeals economically, saving
      about 50% of the energy costs, as well as technically, given straightforward
      operational principles.

PMID- 22414170
TI  - A 14-year-old girl with lissencephaly and craniofacial dysmorphism.

PMID- 22414164
TI  - Patient-reported physical activity questionnaires: a systematic review of content
      and format.
AB  - BACKGROUND: Many patients with chronic illness are limited in their physical
      activities. This systematic review evaluates the content and format of patient
      reported outcome (PRO) questionnaires that measure physical activity in elderly
      and chronically ill populations. METHODS: Questionnaires were identified by a
      systematic literature search of electronic databases (Medline, Embase, PsychINFO
      & CINAHL), hand searches (reference sections and PROQOLID database) and expert
      input. A qualitative analysis was conducted to assess the content and format of
      the questionnaires and a Venn diagram was produced to illustrate this. Each stage
      of the review process was conducted by at least two independent reviewers.
      RESULTS: 104 questionnaires fulfilled our criteria. From these, 182 physical
      activity domains and 1965 items were extracted. Initial qualitative analysis of
      the domains found 11 categories. Further synthesis of the domains found 4 broad
      categories: 'physical activity related to general activities and mobility',
      'physical activity related to activities of daily living', 'physical activity
      related to work, social or leisure time activities', and '(disease-specific)
      symptoms related to physical activity'. The Venn diagram showed that no
      questionnaires covered all 4 categories and that the '(disease-specific) symptoms
      related to physical activity' category was often not combined with the other
      categories. CONCLUSIONS: A large number of questionnaires with a broad range of
      physical activity content were identified. Although the content could be broadly
      organised, there was no consensus on the content and format of physical activity
      PRO questionnaires in elderly and chronically ill populations. Nevertheless, this
      systematic review will help investigators to select a physical activity PRO
      questionnaire that best serves their research question and context.

PMID- 22414171
TI  - Rasch analysis of items from two self-report measures.

PMID- 22414173
TI  - Vasectomy illustrated.

PMID- 22414172
TI  - Hyperbranched double hydrophilic block copolymer micelles of poly(ethylene oxide)
      and polyglycerol for pH-responsive drug delivery.
AB  - We report the synthesis of a well-defined hyperbranched double hydrophilic block
      copolymer of poly(ethylene oxide)-hyperbranched-polyglycerol (PEO-hb-PG) to
      develop an efficient drug delivery system. In specific, we demonstrate the
      hyperbranched PEO-hb-PG can form a self-assembled micellar structure on
      conjugation with the hydrophobic anticancer agent doxorubicin, which is linked to
      the polymer by pH-sensitive hydrazone bonds, resulting in a pH-responsive
      controlled release of doxorubicin. Dynamic light scattering, atomic force
      microscopy, and transmission electron microscopy demonstrated successful
      formation of the spherical core-shell type micelles with an average size of about
      200 nm. Moreover, the pH-responsive release of doxorubicin and in vitro
      cytotoxicity studies revealed the controlled stimuli-responsive drug delivery
      system desirable for enhanced efficiency. Benefiting from many desirable features
      of hyperbranched double hydrophilic block copolymers such as enhanced
      biocompatibility, increased water solubility, and drug loading efficiency as well
      as improved clearance of the polymer after drug release, we believe that double
      hydrophilic block copolymer will provide a versatile platform to develop
      excellent drug delivery systems for effective treatment of cancer.

PMID- 22414174
TI  - 'New kids' in androgen(i) city.

PMID- 22414175
TI  - Travel-associated extended-spectrum beta-lactamase-producing Escherichia coli
      bloodstream infection following transrectal ultrasound-guided prostate biopsy.

PMID- 22414177
TI  - Results from an international multicentre double-blind randomized controlled
      trial on the perioperative efficacy and safety of bipolar vs monopolar
      transurethral resection of the prostate.

PMID- 22414178
TI  - Erlotinib and pemetrexed as maintenance therapy for advanced non-small-cell lung
      cancer: a systematic review and indirect comparison.
AB  - BACKGROUND: Two new agents have recently been licensed as maintenance therapy for
      advanced non-small-cell lung cancer (NSCLC) by the US Food and Drug
      Administration. This paper aims to systematically review the evidence from all
      available clinical trials of erlotinib and pemetrexed as maintenance therapy for
      advanced NSCLC. METHODS: Systematic literature searches were performed in PUBMED,
      EMBASE and Cochrane databases. Abstracts presented at two conferences were also
      researched. The effects of erlotinib and pemetrexed on overall survival and
      progression-free survival were compared using an indirect treatment comparison
      method with placebo or observation as a common comparator. RESULTS: Five
      randomized controlled studies were included. Both interventions offered
      significant advantages for overall survival (OS) and progression-free survival
      (PFS) compared with placebo or observation. Using indirect comparison meta
      analysis, the relative hazards ratio of pemetrexed compared with erlotinib for
      PFS was 0.71 (95% CI 0.60-0.85; p = 0.0001), suggested that pemetrexed was
      superior to erlotinib in terms of progression-free survival. Although relative
      hazards ratio for OS showed no significant difference between the two agents (HR
      0.88; 95% CI 0.71-1.08, p = 0.22). CONCLUSIONS: There is evidence to suggest that
      maintenance treatment with erlotinib or pemetrexed has clinically relevant and
      statistically significant advantages over treatment with placebo or observation
      in patients with advanced NSCLC.

PMID- 22414179
TI  - Epidemiology of severe pediatric adenovirus lower respiratory tract infections in
      Manitoba, Canada, 1991-2005.
AB  - BACKGROUND: Most pediatric adenovirus respiratory infections are mild and
      indistinguishable from other viral causes. However, in a few children, the
      disease can be severe and result in substantial morbidity. We describe the
      epidemiologic, clinical, radiologic features and outcome of adenovirus lower
      respiratory tract infections (LRTI) in Aboriginal and Non-Aboriginal children in
      Manitoba, Canada during the years 1991 and 2005. METHODS: This was a
      retrospective study of 193 children who presented to the department of pediatrics
      at Winnipeg Children's Hospital, Manitoba, Canada with LRTI and had a positive
      respiratory culture for adenovirus. Patients' demographics, clinical and
      radiologic features and outcomes were collected. Adenovirus serotype
      distributions and temporal associations were described. Approximate incidence
      comparisons (detection rates) of adenovirus LRTI among Aboriginal and Non
      Aboriginal children were estimated with 95% confidence intervals. RESULTS:
      Adenovirus infections occurred throughout the year with clusters in the fall and
      winter. Serotypes 1 to 3 were the predominant isolates (two thirds of the cases).
      The infection was more frequent among Canadian Aboriginals, as illustrated in
      2004, where its incidence in children 0-4 years old was 5.6 fold higher in
      Aboriginals (13.51 vs. 2.39 per 10,000, p < 0.000). There were no significant
      differences in length of hospitalization and use of ventilator assistance between
      the two groups (p > 0.185 and p > 0.624, respectively) nor across serotypes (p >
      0.10 and p > 0.05, respectively). The disease primarily affected infants (median
      age, 9.5 months). Most children presented with bronchiolitis or pneumonia, with
      multi-lobar consolidations on the chest x-ray. Chronic (residual) changes were
      documented in 16 patients, with eight patients showing bronchiectasis on the
      chest computerized tomography scan. CONCLUSIONS: Adenovirus infection is
      associated with significant respiratory morbidities, especially in young infants.
      The infection appears to be more frequent in Aboriginal children. These results
      justify a careful follow-up for children with adenovirus LRTI.

PMID- 22414180
TI  - Interobserver agreement in contrast harmonic endoscopic ultrasound.
AB  - BACKGROUND AND AIM: Contrast harmonic endoscopic ultrasound (CH-EUS) was recently
      introduced to clinical practice; its reproducibility among endosonographers is
      unknown. Our aim was to assess the interobserver agreement (IA) in CH-EUS.
      METHODS: Fifteen endosonographers (eight experienced and seven non-experienced)
      from 11 Italian EUS centers evaluated 80 video-cases (40 solid pancreatic
      lesions, 20 pancreatic cystic lesions and 20 submucosal lesions) of CH-EUS,
      according to the degree of enhancement, the pattern of distribution and the
      washout of the contrast agent. IA within each group and between the two groups of
      observers was assessed with the Fleiss kappa statistic. RESULTS: Overall IA was
      moderate for the uptake and fair for the pattern of distribution and the washout.
      In solid pancreatic lesions, IA was moderate for the uptake and fair for the
      pattern and the washout. In cystic pancreatic lesions, IA was uniformly moderate
      for the assessment of uptake, slight for the pattern and fair for the washout. In
      submucosal tumors, IA was substantial for the uptake, slight for the pattern and
      fair for the washout. Non-experienced endosonographers demonstrated, in most
      cases, comparable IA with the experienced ones. CONCLUSIONS: Interobserver
      agreement among endosonographers for CH EUS was satisfactory. In particular,
      overall IA varied from slight to substantial, being fair in the majority of
      cases. Inherent structural features of the lesions, as well as technical
      differences between the variables assessed, could have accounted for the
      fluctuation of the results. Outcomes of IA were reproducible between experienced
      and non-experienced endosonographers.

PMID- 22414182
TI  - Characterization of a novel copper-haem c dissimilatory nitrite reductase from
      Ralstonia pickettii.
AB  - NiRs (nitrite reductases) convert nitrite into NO in the denitrification process.
      RpNiR (Ralstonia pickettii NiR), a new type of dissimilatory Cu-containing NiR
      with a C-terminal haem c domain from R. pickettii, has been cloned, overexpressed
      in Escherichia coli and purified to homogeneity. The enzyme has a subunit
      molecular mass of 50515 Da, consistent with sequence data showing homology to the
      well-studied two-domain Cu NiRs, but with an attached C-terminal haem c domain.
      Gel filtration and combined SEC (size-exclusion chromatography)-SAXS (small angle
      X-ray scattering) analysis shows the protein to be trimeric. The metal content of
      RpNiR is consistent with each monomer having a single haem c group and the two Cu
      sites being metallated by Cu(2+) ions. The absorption spectrum of the oxidized as
      isolated recombinant enzyme is dominated by the haem c. X-band EPR spectra have
      clear features arising from both type 1 Cu and type 2 Cu centres in addition to
      those of low-spin ferric haem. The requirements for activity and low apparent
      K(m) for nitrite are similar to other CuNiRs (Cu-centre NiRs). However, EPR and
      direct binding measurements of nitrite show that oxidized RpNiR binds nitrite
      very weakly, suggesting that substrate binds to the reduced type 2 Cu site during
      turnover. Analysis of SEC-SAXS data suggests that the haem c domains in RpNiR
      form extensions into the solvent, conferring a high degree of conformational
      flexibility in solution. SAXS data yield R(g) (gyration radius) and D(max)
      (maximum particle diameter) values of 43.4 A (1 A=0.1 nm) and 154 A compared with
      28 A and 80 A found for the two-domain CuNiR of Alcaligenes xylosoxidans.

PMID- 22414181
TI  - Silyl glyoxylates. Conception and realization of flexible conjunctive reagents
      for multicomponent coupling.
AB  - This Perspective describes the discovery and development of silyl glyoxylates, a
      new family of conjunctive reagents for use in multicomponent coupling reactions.
      The selection of the nucleophilic and electrophilic components determines whether
      the silyl glyoxylate reagent will function as a synthetic equivalent to the
      dipolar glycolic acid synthon, the glyoxylate anion synthon, or the alpha-keto
      ester homoenolate synthon. The ability to select for any of these reaction modes
      has translated to excellent structural diversity in the derived three- and four
      component coupling adducts. Preliminary findings on the development of catalytic
      reactions using these reagents are detailed, as are the design and discovery of
      new reactions directed toward particular functional group arrays embedded within
      bioactive natural products.

PMID- 22414183
TI  - A single climate driver has direct and indirect effects on insect population
      dynamics.
AB  - Weather drives population dynamics directly, through effects on vital rates, or
      indirectly, through effects on the population's competitors, predators or prey
      and thence on vital rates. Indirect effects may include non-additive interactions
      with density dependence. Detection of climate drivers is critical to predicting
      climate change effects, but identification of potential drivers may depend on
      knowing the underlying mechanisms. For the butterfly Speyeria mormonia, one
      climate driver, snow melt date, has multiple effects on population growth. Snow
      melt date in year t has density-dependent indirect effects. Through frost
      effects, early snow melt decreases floral resources, thence per-capita nectar
      availability, which determines fecundity in the lab. Snow melt date in year t + 1
      has density-independent direct effects. These effects explain 84% of the
      variation in population growth rate. One climate parameter thus has multiple
      effects on the dynamics of a species with non-overlapping generations, with one
      effect not detectable without understanding the underlying mechanism.

PMID- 22414184
TI  - Photoinduced switching from living radical polymerization to a radical coupling
      reaction mediated by organotellurium compounds.
AB  - An efficient and simple method for the synthesis of symmetric macromolecules by
      photoinduced switching from radical polymerization to a radical coupling reaction
      is reported. Structurally well-defined telechelic polyisoprenes and ABA-triblock
      copolymers were prepared by successive organotellurium-mediated living radical
      polymerization (TERP) under thermal conditions, followed by a polymer-end radical
      coupling reaction under photoirradiation.

PMID- 22414185
TI  - Unraveling functional abdominal bloating and distension: the role of thoraco
      abdominal accommodation and a physical sign to aid its detection.
AB  - Bloating and distension are common complaints in patients with irritable bowel
      syndrome of which the cause has remained elusive, although it has been shown that
      the obvious explanation of excessive gas is unlikely. The recent application of
      technologies such as the gas challenge technique, abdominal inductance
      plethysmography, CT scanning, as well as electromyography of the diaphragm and
      anterior abdominal wall, have allowed the situation to be slowly unraveled. It is
      now seems probable that the pathophysiology of bloating and distension are subtly
      different with the former having a sensory component whereas mechanical factors,
      such as disordered abdominal accommodation, contribute more to the latter.

PMID- 22414186
TI  - Frequency analysis may distinguish the effects of calcium antagonists on
      mechanical and electrical activity.

PMID- 22414188
TI  - Comparison of worm development and host immune responses in natural hosts of
      Schistosoma japonicum, yellow cattle and water buffalo.
AB  - BACKGROUND: Yellow cattle and water buffalo are two of the most important natural
      hosts for Schistosoma japonicum in China. Previous observation has revealed that
      yellow cattle are more suited to the development of S. japonicum than water
      buffalo. Understanding more about the molecular mechanisms involved in worm
      development, as well as the pathological and immunological differences between
      yellow cattle and water buffalo post infection with S japonicum will provide
      useful information for the vaccine design and its delivery procedure. RESULTS:
      The worm length (p < 0.01), worm recovery rate (p < 0.01) and the percentage of
      paired worms (p < 0.01) were significantly greater in yellow cattle than those in
      water buffalo. There were many white egg granulomas in the livers of yellow
      cattle, but fewer were observed in water buffalo at 7 weeks post infection. The
      livers of infected yellow cattle contained significantly increased accumulation
      of inflammatory cells, and the schistosome eggs were surrounded with large
      amounts of eosinophil infiltration. In contrast, no hepatocyte swelling or
      lymphocyte infiltration, and fewer white blood cells, was observed in water
      buffalo. The percentage of CD4+ T cells was higher in yellow cattle, while the
      percentage of CD8+ T cells was higher in water buffalo from pre-infection to 7 w
      post infection. The CD4/CD8 ratios were decreased in both species after challenge
      with schistosomes. Comparing with water buffalo, the IFN-gamma level was higher
      and decreased significantly, while the IL-4 level was lower and increased
      gradually in yellow cattle from pre-infection to 7 w post infection. CONCLUSIONS:
      In this study, we confirmed that yellow cattle were more suited to the
      development of S. japonicum than water buffalo, and more serious pathological
      damage was observed in infected yellow cattle. Immunological analysis suggested
      that CD4+ T cells might be an integral component of the immune response and might
      associate with worm development in yellow cattle. A shift from Th1 to Th2 type
      polarized immunity was only shown clearly in schistosome-infected yellow cattle,
      but no shift in water buffalo. The results provide valuable information for
      increased understanding of host-schistosome interactions, and for control of
      schistosomiasis.

PMID- 22414189
TI  - Headache currents commentary.
AB  - What Happens to the Old Headache Medicines? Rapoport AM, MD. Old headache
      medicines never die; they either fade away or come back in disguise. The disguise
      is often a new route of administration, which may work better, faster, more
      completely, with fewer adverse events, and/or have certain other advantages. The
      clinical aspects of 3 of the oldest headache medicines (ergotamine tartrate,
      dihydroergotamine, and methysergide) will be discussed here. Sumatriptan will
      then be discussed as the prototype of the newest category of acute care therapy
      (triptans) for migraine. It will be compared with the older medications, and the
      new forms being developed will be briefly discussed. Diclofenac potassium for
      oral solution will be mentioned as the newest drug approved for migraine by the
      Food and Drug Administration and a possible alternative to triptans in patients
      with frequent headaches or those with contraindications to vasoconstrictors.
      Dihydroergotamine, Ergotamine, Methysergide and Sumatriptan - Basic Science in
      Relation to Migraine Treatment. Dahlof C, Maassen Van Den Brink A. The 5
      hydroxytryptamine (5-HT) receptor family mediates the effects of several drugs
      highly effective in migraine primarily by activating 5-HT(1B) , 5-HT(1D) , and 5
      HT(1F) receptors. Ergotamine, dihydroergotamine and methysergide, as well as the
      "triptan" sumatriptan, are all agonists for these receptors. The receptor profile
      and degree of selectivity of these 4 drugs differ, which is reflected by their
      side effects that limit their use in the acute and prophylactic treatment of
      migraine. The acute antimigraine efficacy of these remedies is very much
      dependent on the formulation used where, in general, parenteral formulations are
      more effective in relieving the symptoms of a migraine attack.

PMID- 22414190
TI  - Cold electron source with an electron multiplier illuminated by ultraviolet
      photons.
AB  - A cold electron source has been developed using a microchannel plate (MCP)
      electron multiplier. Primary electron emission is initiated by illumination with
      ultraviolet photons from a diode. Final electron emission currents of up to 10
      MUA in continuous wave (CW) mode and 10 mA in pulsed mode have been achieved from
      a MCP with an active diameter of 5.5 mm. Electron emission generated by UV
      photons with a wavelength of 260 nm has been shown to be about 30 times more
      efficient than emission generated by photons with a wavelength of 300 nm.
      Application of this cold electron source in mass spectrometry is discussed.

PMID- 22414191
TI  - Identification of citrinin as the defence metabolite of Penicillium corylophilum
      stressed with the antagonist fungus Beauveria bassiana.
AB  - Penicillium corylophilum isolated from mosquitoes was cultivated in liquid media
      leading to the first reported identification of citrinin (1a) as one metabolic
      component of this fungus. The produced amount of 1a indicated this compound as
      the most abundant secondary metabolite of this fungus. Stressing the culture of
      P. corylophilum with the presence of the antagonistic fungus Beauveria bassiana
      increased in 65% the production of 1a. Similar results were obtained with the
      presence of other fungi in the culture media, indicating that citrinin is the
      main defence metabolite of P. corylophilum. In agreement with this conclusion,
      citrinin showed a reasonable fungicidal activity against Colletotrichum
      gloeosporioides and B. bassiana.

PMID- 22414192
TI  - Threat advantage: perception of angry and happy dynamic faces across cultures.
AB  - The current study tested whether the perception of angry faces is cross
      culturally privileged over that of happy faces, by comparing perception of the
      offset of emotion in a dynamic flow of expressions. Thirty Chinese and 30
      European-American participants saw movies that morphed an anger expression into a
      happy expression of the same stimulus person, or vice versa. Participants were
      asked to stop the movie at the point where they ceased seeing the initial
      emotion. As expected, participants cross-culturally continued to perceive anger
      longer than happiness. Moreover, anger was perceived longer in in-group than in
      out-group faces. The effects were driven by female rather than male targets.
      Results are discussed with reference to the important role of context in emotion
      perception.

PMID- 22414193
TI  - Isolation and initial characterization of a novel type of Baeyer-Villiger
      monooxygenase activity from a marine microorganism.
AB  - A novel type of Baeyer-Villiger monooxygenase (BVMO) has been found in a marine
      strain of Stenotrophomonas maltophila strain PML168 that was isolated from a
      temperate intertidal zone. The enzyme is able to use NADH as the source of
      reducing power necessary to accept the atom of diatomic oxygen not incorporated
      into the oxyfunctionalized substrate. Growth studies have establish that the
      enzyme is inducible, appears to serve a catabolic role, and is specifically
      induced by one or more unidentified components of seawater as well as various
      anthropogenic xenobiotic compounds. A blast search of the primary sequence of the
      enzyme, recovered from the genomic sequence of the isolate, has placed this
      atypical BVMO in the context of the several hundred known members of the
      flavoprotein monooxygenase superfamily. A particular feature of this BVMO lies in
      its truncated C-terminal domain, which results in a relatively small protein (357
      amino acids; 38.4 kDa). In addition, metagenomic screening has been conducted on
      DNA recovered from an extensive range of marine environmental samples to gauge
      the relative abundance and distribution of similar enzymes within the global
      marine microbial community. Although low, abundance was detected in samples from
      many marine provinces, confirming the potential for biodiscovery in marine
      microorganisms.

PMID- 22414194
TI  - Chiral sensing using an achiral europium(III) complex by induced circularly
      polarized luminescence.
AB  - [Eu(bda)(2)](-) (bda = 2,2'-bipyridine-6,6'-dicarboxylic acid) produces intense
      circularly polarized luminescence (CPL) in aqueous solutions in the presence of
      (S)-2-pyrrolidone-5-carboxylic acid upon UV irradiation, although the molecular
      structure of the europium(III) complex is achiral. The mechanism for the
      induction of CPL was preliminarily attributed to distortions induced by
      association with an amino acid to generate chirality in the achiral complex. The
      optical anisotropy factor (g(lum) value) for the (5)D(0) -> (7)F(1) transition
      was 0.03 in the presence of 1.0 mol dm(-3) of the amino acid. Analysis of the CPL
      intensity as a function of the amino acid concentration gave an association
      constant between those of [Eu(bda)(2)](-) and the amino acid, K(aso) = 0.55 +/-
      0.09 mol(-1) dm(3). These results demonstrate the potential of [Eu(bda)(2)](-) to
      act as a luminescent chiral-sensing reagent in microscopic spectroscopy.

PMID- 22414195
TI  - Cord blood immune status: predicting health or allergy?

PMID- 22414196
TI  - We call for iCAALL: International Collaboration in Asthma, Allergy and
      Immunology.

PMID- 22414197
TI  - Classical pattern recall tests and the prospective nature of expert performance.
AB  - It is well established that experts are particularly adept at recalling and/or
      recognizing the key features of domain-relevant patterns. We compared the recall
      performance of expert and novice basketball players when viewing static and
      moving patterns. A novel method of analysis was used where the accuracy of the
      participants in recalling player positions was compared to actual player
      positions both at the final frame of pattern presentation and at 50 successive 40
      ms increments thereafter. Experts encoded the locations of the players in both
      the static and moving patterns significantly further in advance of their actual
      finishing point than did nonexperts. Experts' use of an anticipatory encoding
      process, which was of a magnitude unmatched by nonexperts, suggests that many
      previous investigations may have underestimated the extent of the expert
      advantage in pattern recall.

PMID- 22414198
TI  - Effectiveness of peer-led self-management coaching for patients recently
      diagnosed with Type 2 diabetes mellitus in primary care: a randomized controlled
      trial.
AB  - AIMS: To study the effectiveness of a peer-led self-management coaching
      intervention in recently diagnosed patients with Type 2 diabetes. METHODS:
      Randomized controlled trial of recently diagnosed patients with Type 2 diabetes
      from 54 participating general practices. The intervention group received three
      home visits by an experienced peer (expert patient) who adhered to the
      recommended treatment and lifestyle guidelines. Together with their expert
      patient, participants set feasible goals and these were evaluated in the next
      visit. Participants in the control group received care as usual. At baseline, 3
      months and 6 months post-intervention, participants completed a questionnaire
      measuring changes in self-efficacy, coping, physical activity, dietary habits,
      psychological well-being, depressive symptoms and diabetes related distress.
      RESULTS: In total, 327 patients were eligible for inclusion in the study of which
      133 consented to participate. In participating patients, self-efficacy, coping
      and saturated fat intake improved significantly over time. Analyses of
      participants with low self-efficacy at baseline (25th percentile: 44) revealed a
      significant time * group difference, F = 3.71; P = 0.03. Participants who
      reported low psychological well-being at baseline increased substantially
      throughout the study (F = 23.84; P < 0.01) but no significant time * group
      differences were found. CONCLUSIONS: A peer-led self-management coaching
      programme for recently diagnosed patients with Type 2 diabetes improved self
      efficacy of patients experiencing low self-efficacy shortly after diagnosis.

PMID- 22414199
TI  - Patients' lived experiences of a reduced intake of food and drinks during
      illness: a literature review.
AB  - AIM: This study aims to identify patients' lived experiences of having a reduced
      intake of food and drink during illness, through a literature review. METHODS:
      Scientific studies were selected through a systematic search of CINAHL, PubMed,
      SweMed, British Nursing Index, Psycinfo and EMBASE. A deductive thematic analysis
      was performed on the studies included. The analysis provided three main themes:
      (i) serving of food and drink - patient experiences. (ii) Modifications related
      to illness - patient experiences. (iii) Nutritional care provided by healthcare
      professionals nutritional care - patient experiences. FINDINGS: Generally
      speaking, the findings showed high satisfaction with the food served at
      hospitals. However, patients' individual tastes and preferences as to when and
      where to eat were found to affect their intake of food and drink. Physical
      changes because of illness were stated as the main reason for the patients' lived
      experiences of a reduced intake of food and drink. These experiences seemed to be
      related to negative feelings, such as anxiety and shame during meals.
      Furthermore, the literature review revealed a lack of professional assistance
      during meals and insufficient guidance on how to handle specific nutritional
      problems. CONCLUSIONS: Patients expect committed nursing care in regard to
      nutritional advice during illness and assistance in meal-related situations.
      Nurses need to refocus on fundamental caring.

PMID- 22414200
TI  - Measurement equivalence of the SF-36 in the Canadian Multicentre Osteoporosis
      Study.
AB  - BACKGROUND: Studies that compare health-related quality of life (HRQOL) and other
      patient-reported outcomes in different populations rest on the assumption that
      the measure has equivalent psychometric properties across groups. This study
      examined the measurement equivalence (ME) of the 36-item Medical Outcomes Study
      Short Form Survey (SF-36), a widely-used measure of HRQOL, by sex and race in a
      population-based Canadian sample. FINDINGS: SF-36 data were from the Canadian
      Multicentre Osteoporosis Study, a prospective cohort study that randomly sampled
      adult men and women from nine sites across Canada. Confirmatory factor analysis
      (CFA) techniques were used to test hypotheses about four forms of ME, which are
      based on equality of the factor loadings, variances, covariances, and intercepts.
      Analyses were conducted for Caucasian and non-Caucasian females (n = 6,539) and
      males (n = 2,884). CFA results revealed that a measurement model with physical
      and mental health factors provided a good fit to the data. All forms of ME were
      satisfied for the study groups. CONCLUSIONS: The results suggest that sex and
      race do not influence the conceptualization of a general measure of HRQOL in the
      Canadian population.

PMID- 22414201
TI  - Synthesis of imidazo[4,5-b]pyridines and imidazo[4,5-b]pyrazines by palladium
      catalyzed amidation of 2-chloro-3-amino-heterocycles.
AB  - A facile synthesis of imidazo[4,5-b]pyridines and -pyrazines is described using a
      Pd-catalyzed amide coupling reaction. This reaction provides quick access to
      products with substitution at N1 and C2. A model system relevant to the natural
      product pentosidine has been demonstrated, as well as the total synthesis of the
      mutagen 1-Me-5-PhIP.

PMID- 22414202
TI  - Ambulatory activity of children with cerebral palsy: which characteristics are
      important?
AB  - AIM: To assess ambulatory activity of children with cerebral palsy (CP), aged 7
      to 13 years, and identify associated characteristics. METHOD:   Sixty-two
      children with spastic CP (39 males, 23 females; mean age 10y 1mo, SD 1y 8mo; age
      range 7-13y), classified as Gross Motor Function Classification System (GMFCS)
      levels I to III, participated. Ambulatory activity was measured during 1 week
      with a StepWatch activity monitor as steps per day, and time spent at medium and
      high step rates. Multiple linear regression analyses were performed following a
      backward selection procedure until only independent variables with p<0.05
      remained in the model. Ambulatory activity outcome parameters served as dependent
      variables, and disease, personal, and environmental characteristics as
      independent variables. Ambulatory activity was corrected for body height.
      RESULTS: Children took more steps during school days (5169 steps, SD 1641) than
      during weekend days (4158 steps, SD 2048; p<0.001). Higher GMFCS level, bilateral
      CP, and higher age were associated with lower ambulatory activity on school days
      (R(2) ranged from 43-53%), whereas bilateral CP, higher age, and no sport club
      participation were associated with lower ambulatory activity in the weekend (R(2)
      ranged from 21-42%). Correcting for body height decreased the association with
      age. INTERPRETATION: Interventions should focus at increasing physical activity
      at the weekend for children with bilateral spastic CP.

PMID- 22414203
TI  - Retraction: Screening and identification of a renal carcinoma specific peptide
      from a phage display peptide library.

PMID- 22414204
TI  - Tunnel field-effect transistors based on InP-GaAs heterostructure nanowires.
AB  - We present tunneling field-effect transistors fabricated from InP-GaAs
      heterostructure nanowires with an n-i-p doping profile, where the intrinsic InP
      region is modulated by a top gate. The devices show an inverse subthreshold slope
      down to 50 mV/dec averaged over two decades with an on/off current ratio of
      approximately 10(7) for a gate voltage swing (V(GS)) of 1 V and an on-current of
      2.2 MUA/MUm. Low-temperature measurements suggest a mechanism of trap-assisted
      tunneling, possibly explained by a narrow band gap segment of InGaAsP.

PMID- 22414205
TI  - Electrodeposition of a biopolymeric hydrogel: potential for one-step protein
      electroaddressing.
AB  - The electrodeposition of hydrogels provides a programmable means to assemble soft
      matter for various technological applications. We report an anodic method to
      deposit hydrogel films of the aminopolysaccharide chitosan. Evidence suggests the
      deposition mechanism involves the electrolysis of chloride to generate reactive
      chlorine species (e.g., HOCl) that partially oxidize chitosan to generate
      aldehydes that can couple covalently with amines (presumably through Schiff base
      linkages). Chitosan's anodic deposition is controllable spatially and temporally.
      Consistent with a covalent cross-linking mechanism, the deposited chitosan
      undergoes repeated swelling/deswelling in response to pH changes. Consistent with
      a covalent conjugation mechanism, proteins could be codeposited and retained
      within the chitosan film even after detergent washing. As a proof-of-concept, we
      electroaddressed glucose oxidase to a side-wall electrode of a microfabricated
      fluidic channel and demonstrated this enzyme could perform electrochemical
      biosensing functions. Thus, anodic chitosan deposition provides a reagentless,
      single-step method to electroaddress a stimuli-responsive and biofunctionalized
      hydrogel film.

PMID- 22414206
TI  - The effects of depression and use of antidepressive medicines during pregnancy on
      the methylation status of the IGF2 imprinted control regions in the offspring.
AB  - In utero exposures to environmental factors may result in persistent epigenetic
      modifications affecting normal development and susceptibility to chronic diseases
      in later life. We explored the relationship between exposure of the growing fetus
      to maternal depression or antidepressants and DNA methylation at two
      differentially methylated regions (DMRs) of the imprinted Insulin-like Growth
      Factor 2 (IGF2) gene. Aberrant DNA methylation at the IGF2 and neighboring H19
      DMRs has been associated with deregulated IGF2 expression, childhood cancers and
      several chronic diseases during adulthood. Our study population is comprised of
      pregnant mothers and their newborns (n = 436), as part of the Newborn Epigenetics
      Study (NEST). A standardized questionnaire was completed and medical record data
      were abstracted to ascertain maternal depression and antidepressive drug use. DMR
      methylation levels in umbilical cord blood leukocytes were quantified using
      pyrosequencing. From the 436 newborns, laboratory data were obtained for 356
      individuals at the IGF2 DMRs, and for 411 individuals at the H19 DMRs; about half
      of each group was African American or Caucasian. While overall no association
      between depression and methylation profiles was found, we observed a significant
      hypermethylation of the H19 DMRs in newborns of African American (n = 177) but
      not Caucasian (n = 168) mothers who reported the use of antidepressive drugs
      during pregnancy (beta = +6.89, p = 0.01). Of note, our data reveal a race
      independent association between smoking during pregnancy and methylation at the
      IGF2 DMR (+3.05%, p = 0.01). In conclusion, our findings suggest a race-dependent
      response related to maternal use of antidepressants at one of the IGF2 DMRs in
      the offspring.

PMID- 22414207
TI  - Conservative and radiological management of simple renal cysts: a comprehensive
      review.
AB  - What's known on the subject? and What does the study add? Simple renal cysts are
      a common entity, which may need observation and follow-up or treatment. The
      study, for the first time, systematically reviews the indications for follow-up
      or radiological treatment of simple renal cysts. To review the conservative and
      radiological management of simple renal cysts a systematic literature review was
      performed. Simple renal cysts are commonly found in the adult population.
      Increasing age is highly associated with its incidence. When they remain
      asymptomatic they require neither treatment nor follow-up. When the shape of the
      cyst is slightly irregular follow-up is mandatory to exclude malignant
      progression. Symptomatic cysts require intervention. Ultrasound or computed
      tomography guidance have been effectively used for cyst puncture. However, simple
      fluid aspiration is ineffective leading to cyst recurrence. Aspiration should be
      accompanied with the injection of a sclerosing agent to destroy renal cyst
      epithelium. Several issues such as the ultimate technique and agent remain to be
      clarified. High rates of cyst disappearance and long-lasting cyst volume
      reduction have been reported with the use of various sclerosants. Ethanol in high
      concentrations and multiple injections is more commonly used with new agents
      showing similar efficacy and better complication profile. Studies comparing
      radiological intervention to surgical excision are lacking. Simple renal cysts
      may not require treatment when asymptomatic. Radiological intervention with the
      use of sclerosants needs further evaluation and comparison with other treatment
      methods.

PMID- 22414208
TI  - Structure and dynamics of P,N-containing heterocycles and their metal complexes
      in solution.
AB  - Conformations and dynamics of 1,5-diaza-3,7-diphosphacyclooctane (1) with chiral
      l-menthyl substituents on the phosphorus atoms and several metal complexes
      thereof were investigated by a variety of DNMR methods. In solution 1 adopts a
      C(2) symmetrical "crown"-like conformation (CW) and the conformational preference
      and dynamics of the complexes depend on the type of metal: for the Cu complex the
      CW form is preferred, whereas the Pd, Pt, or Mo complexes exist in an equilibrium
      of two "chair-boat"-like conformations (CB/CB*). The barriers of interconversion
      between these two conformations for the Pd and Pt complexes are about 2 times
      higher than for the Mo complex. Quantum chemical calculations (B3LYP/6-31G(d))
      are in agreement with experimental findings.

PMID- 22414209
TI  - An institutional perspective on the impact of recent antibiotic exposure on
      length of stay and hospital costs for patients with gram-negative sepsis.
AB  - BACKGROUND: Prior antibiotic exposure has been associated with the emergence of
      antibiotic resistance in subsequent bacterial infections, whose outcomes are
      typically worse than similar infections with more antibiotic susceptible
      infections. The influence of prior antibiotic exposure on hospital length of stay
      (LOS) and costs in patients with severe sepsis or septic shock attributed to Gram
      negative bacteremia has not been previously examined. METHODS: A retrospective
      cohort study of hospitalized patients (January 2002-December 2007) was performed
      at Barnes-Jewish Hospital, a 1200-bed urban teaching hospital. Patients with Gram
      negative bacteremia complicated by severe sepsis or septic shock had data
      abstraction from computerized medical records. We examined a consecutive cohort
      of 754 subjects (mean age 59.3 +/- 16.3 yrs, mean APACHE II 23.7 +/- 6.7).
      RESULTS: Escherichia coli (30.8%), Klebsiella pneumoniae (23.2%), and Pseudomonas
      aeruginosa (17.6%) were the most common organisms isolated from blood cultures.
      310 patients (41.1%) had exposure to antimicrobial agents in the previous 90
      days. Patients with recent antibiotic exposure had greater inappropriate initial
      antimicrobial therapy (45.4% v. 21.2%; p < 0.001) and hospital mortality (51.3%
      v. 34.0%; p < 0.001) compared to patients without recent antibiotic exposure. The
      unadjusted median LOS (25th percentile, 75th percentile) following sepsis onset
      in patients with prior antimicrobial exposure was 13.0 days (5.0 days, 24.0 days)
      compared to 8.0 days (5.0 days, 14.0 days) in those without prior antimicrobial
      exposure (p < 0.001). In a Cox model controlling for multiple confounders, prior
      antibiotic exposure independently correlated with remaining hospitalized
      (Adjusted hazard ratio: 1.473, 95% CI: 1.297-1.672, p < 0.001). Adjusting for
      potential confounders indicated that prior antibiotic exposure independently
      increased median attributable LOS by 5.0 days. Similarly, total hospital costs
      following sepsis onset was significantly greater among patients with prior
      antimicrobial exposure (median values: $94,737 v. $21,329; p < 0.001).
      CONCLUSIONS: Recent antibiotic exposure is associated with increased LOS and
      hospital costs in Gram-negative bacteremia complicated by severe sepsis or septic
      shock. Clinicians and hospital administrators should consider the potential
      impact of recent antibiotic exposure when formulating empiric treatment decisions
      for patients with serious infections attributed to Gram-negative bacteria.

PMID- 22414210
TI  - Characterization of the evolutionarily conserved iron-sulfur cluster of
      sirohydrochlorin ferrochelatase from Arabidopsis thaliana.
AB  - Sirohaem is a cofactor of nitrite and sulfite reductases, essential for
      assimilation of nitrogen and sulfur. Sirohaem is synthesized from the central
      tetrapyrrole intermediate uroporphyrinogen III by methylation, oxidation and
      ferrochelation reactions. In Arabidopsis thaliana, the ferrochelation step is
      catalysed by sirohydrochlorin ferrochelatase (SirB), which, unlike its
      counterparts in bacteria, contains an [Fe-S] cluster. We determined the cluster
      to be a [4Fe-4S] type, which quickly oxidizes to a [2Fe-2S] form in the presence
      of oxygen. We also identified the cluster ligands as four conserved cysteine
      residues located at the C-terminus. A fifth conserved cysteine residue, Cys(135),
      is not involved in ligating the cluster directly, but influences the oxygen
      sensitivity of the [4Fe-4S] form, and possibly the affinity for the substrate
      metal. Substitution mutants of the enzyme lacking the Fe-S cluster or Cys(135)
      retain the same specific activity in vitro and dimeric quaternary structure as
      the wild-type enzyme. The mutant variants also rescue a defined Escherichia coli
      sirohaem-deficient mutant. However, the mutant enzymes cannot complement
      Arabidopsis plants with a null AtSirB mutation, which exhibits post-germination
      arrest. These observations suggest an important physiological role for the Fe-S
      cluster in Planta, highlighting the close association of iron, sulfur and
      tetrapyrrole metabolism.

PMID- 22414211
TI  - Distribution trends of gastric polyps: an endoscopy database analysis of 24 121
      northern Chinese patients.
AB  - BACKGROUND AND AIM: Traditionally the most common gastric polyps are hyperplastic
      polyps (HPs). However, in the last two decades, fundic gland polyps (FGPs) have
      greatly increased in Western countries. We aimed to re-evaluate and compare the
      distribution of gastric polyps in a northern Chinese population in 2000 and 2010.
      METHODS: Consecutive patients with gastric polyps detected in 2000 and 2010 were
      analyzed and biopsies were re-evaluated. Data including patients' age, sex,
      symptoms and the number, size, location, Helicobacter pylori (H. pylori)
      infection of polyps were recorded. RESULTS: A total of 6784 and 17 337 patients
      underwent esophagogastroduodenoscopy in 2000 and 2010, 68 and 183 patients were
      diagnosed with gastric polyps, respectively. H. pylori infection decreased from
      54.4% to 37.7% (P = 0.017). Overall, spectrum of gastric polyps changed (P <
      0.001). HPs accounted for 28.3% and decreased from 48.5% to 20.8%,
      adenoma/carcinoma and inflammatory polyps also decreased. FGPs were present in
      50.6% and increased from 8.8% to 66.1%. The location of polyps was also changed
      with an increase of polyps in gastric corpus. There was a high proportion of FGPs
      in females, while adenomas/adenocarcinomas were more common in males. The
      distribution pattern was similar in young and elderly patients. CONCLUSIONS:
      Spectrum change of gastric polyps was observed over the past 10 years in the
      northern Chinese population most likely due to the higher proportion of FGPs.
      Further studies are required to investigate the reasons and confirm whether it
      will lead to a different management strategy in China.

PMID- 22414212
TI  - Monitoring airborne biotic contaminants in the indoor environment of pig and
      poultry confinement buildings.
AB  - Given the growing concerns over human and animal health issues related to
      confined animal feeding operations, an in-depth examination is required to
      monitor for airborne bacteria and associated antibiotic resistance genes. Our 16S
      rRNA-based pyrosequencing revealed that the airborne microbial community skewed
      towards a higher abundance of Firmicutes (> 59.2%) and Bacteroidetes (4.2-31.4%)
      within the confinement buildings, while the office environment was predominated
      by Proteobacteria (55.2%). Furthermore, bioaerosols in the confinement buildings
      were sporadically associated with genera of potential pathogens, and these genera
      were more frequently observed in the bioaerosols of pig and layer hen confinement
      than the turkey confinement buildings and office environment. High abundances of
      tetracycline resistance genes (9.55 * 10(2)  to 1.69 * 10(6)  copies ng(-1)  DNA)
      were also detected in the bioaerosols sampled from confinement buildings.
      Bacterial lineages present in the poultry bioaerosols clustered apart from those
      present in the pig bioaerosols and among the different phases of pig production,
      suggesting that different livestock as well as production phase were associated
      with a distinct airborne microbial community. By understanding the diversity of
      biotic contaminants associated with the different confinement buildings, this
      study facilitates the implementation of better management strategies to minimize
      potential health impacts on both livestock and humans working in this
      environment.

PMID- 22414213
TI  - Preparation of alkyl-modified silicon nanosheets by hydrosilylation of layered
      polysilane (Si6H6).
AB  - Alkyl-modified crystalline silicon nanosheets 2 were synthesized and maintained
      the crystal structure of a Si(111) plane, in which the dangling silicon bond is
      stabilized by capping with the alkyl group. 2 was characterized using UV-vis,
      Fourier transform-infrared, and X-ray photoelectron spectroscopies; X-ray
      diffraction; and X-ray absorption near edge structure analysis. A model structure
      is proposed that has a periodicity through the nanosheet surface.

PMID- 22414214
TI  - Emotions in sexual morality: testing the separate elicitors of anger and disgust.
AB  - Recent work suggests that negative moral judgements of sexual activities are
      informed by disgust and anger. A correlational study (N=62) and an experiment
      (N=176) examined the specific antecedents that elicit these distinct, though
      correlated, moral emotions. Participants in Study 1 rated their emotional
      reactions to, and judgements of, 10 sexual scenarios. Across scenarios,
      judgements of abnormality predicted disgust independent of anger, and judgements
      of harm/rights violation predicted anger independent of disgust. Study 2
      replicated these results in an experimental design. Participants rated their
      emotions and judgements in response to behaviours that varied in degree of
      potential sexual morality violation (non-sexual, heterosexual, homosexual) and
      rights violation (no harm, indirect harm, direct harm). Judgement of rights
      violation mediated the effects of harm on anger. Judgements of abnormality, but
      not other antecedents proposed to elicit moral disgust, mediated the effects of
      sexual immorality on disgust.

PMID- 22414215
TI  - Adrenocortical carcinoma: an unusual genetic cause!

PMID- 22414216
TI  - Na2EuAs2S5, NaEuAsS4, and Na4Eu(AsS4)2: controlling the valency of arsenic in
      polysulfide fluxes.
AB  - The reactivity of europium with As species in Lewis basic alkali-metal
      polysulfide fluxes was investigated along with compound formation and the
      As(3+)/As(5+) interplay vis-a-vis changes in the flux basicity. The compound
      Na(2)EuAs(2)S(5) containing trivalent As(3+) is stabilized from an arsenic-rich
      polysulfide flux. It crystallizes in the monoclinic centrosymmetric space group
      P2(1)/c. Na(2)EuAs(2)S(5) has [As(2)S(5)](4-) units, built of corner sharing
      AsS(3) pyramids, which are coordinated to Eu(2+) ions to give a two-dimensional
      (2D) layered structure. A sodium polysulfide flux with comparatively less arsenic
      led to the As(5+) containing compounds NaEuAsS(4) (orthorhombic, Ama2) and
      Na(4)Eu(AsS(4))(2) (triclinic, P1) depending on Na(2)S/S ratio. The NaEuAsS(4)
      and Na(4)Eu(AsS(4))(2) have a three-dimensional (3D) structure built of
      [AsS(4)](3-) tetrahedra coordinated to Eu(2+) ions. All compounds are
      semiconductors with optical energy gaps of ~2 eV.

PMID- 22414217
TI  - Improving outcomes for psychoses through the use of psycho-education; preliminary
      findings.
AB  - A psycho-education programme is provided for patients suffering from psychosis in
      Scotland's only high secure hospital. An 18-month pilot study was carried out
      with consecutive case sample (treatment group) and 'treatment as usual'
      comparison group (control group). Pre, post and 6-month follow-up assessments
      were carried out. A range of outcome measures were used, including two measures
      of knowledge: a self-report assessment tool - Forensic Assessment of Knowledge
      Tool and the Understanding Medication Questionnaire. Other measures were used to
      establish level of insight, Schedule for the Assessment of Insight and assess
      mental state [Positive and Negative Syndrome Scale (PANSS)]. Results from (n =
      48) participants indicate no statistical difference between the treatment and
      control group scores on any assessment prior to commencement of the intervention,
      indicating a well-matched sample group. However, all four assessments showed
      statistically significant changes post group. Treatment group showed an ability
      to improve knowledge and retain information about psychosis, which may account
      for their improved mental state and level of insight. Despite methodological
      limitations and a small sample group, this project has given an early indication
      of the positive value of this psycho-education programme in a forensic setting.

PMID- 22414218
TI  - Severe hypoglycaemia from repaglinide-brotizolam drug interaction: a case report
      and literature review.

PMID- 22414219
TI  - Arthroscopic anatomical double-bundle anterior cruciate ligament reconstruction
      for asian patient using a bone-patellar tendon-bone and gracilis tendon composite
      autograft: a technical note.
AB  - BACKGROUND: Recent years have seen anterior cruciate ligament (ACL)
      reconstruction being performed in a broad range of patients, regardless of age,
      sex and occupation, thanks to great advances in surgical techniques, surgical
      instruments and basic research. In cases of ACL reconstruction, bone-patellar
      tendon-bone (BTB) graft or hamstring graft are frequency used. However, potential
      complications associated with tunnel enlargement due to soft tissue graft such as
      hamstring were reported. On the other hand, an altered rotational axis resulting
      in significantly greater translation of the lateral compartment in the single
      bundle compared with double bundle ACL reconstruction was reported. METHOD AND
      PROCEDURE: A reconstruction procedure was modified for the ACL using a double
      bundle that is the combination of BTB and gracilis tendon composite autograft.
      Two tibial and two femoral bone tunnels are used to reconstruct two bundles of
      ACL; an anteromedial bundle (AMB) and a posterolateral bundle (PLB). The femoral
      bone tunnels are created just posterior to the resident's ridge. The tibial bone
      tunnels are created at the center of AM and PL tibial attachment, respectively.
      BTB is fixed in the AM tunnels produced on the anatomical points of tibia and
      femur. The gracilis graft is fixed in an anatomical PL tunnel produced. The mean
      width of BTB is 7 mm, since10 mm graft is sometimes not suitable for patients,
      especially small Asian people and females. For these patients, 10 mm graft is
      bigger than one third of patella tendon width. CONCLUSION: The devised surgical
      procedure based on a combination of BTB and gracilis autograft is suitable
      reconstruction method for patients who have small or medium width of patellar
      tendon such as Asian people and females. This technique is also applicable to
      revision surgery.

PMID- 22414220
TI  - Houttuynoids A-E, anti-herpes simplex virus active flavonoids with novel
      skeletons from Houttuynia cordata.
AB  - Houttuynoids A-E (1-5), a new type of flavonoid with houttuynin tethered to
      hyperoside, and their presumed biosynthetic precursor hyperoside (6) were
      isolated from the whole plant of Houttuynia cordata. Their structures were
      elucidated by analysis of 1D and 2D NMR. A hypothetical biogenetic pathway for
      houttuynoids A-E was proposed. Compounds 1-5 exhibited potent anti-HSV (herpes
      simplex viruses) activity.

PMID- 22414221
TI  - TGFBR1 mutations associated with Loeys-Dietz syndrome are inactivating.
AB  - To assess the effect of Loeys-Dietz syndrome (LDS) mutations affecting TGFBetaR1
      a selection of seven disease-associated amino acid substitutions were introduced
      into wild type TGFbetaR1 and constitutively active TGFbetaR1(T204D). Receptor
      function was tested by co-transfection with a luciferase reporter or EGFP-tagged
      SMAD2 in HEK293 cells. All of the mutations were found to be inactivating for
      canonical TGF-beta signaling. Differences in residual activity were not found to
      correlate with disease subtype. In co-transfection experiments with equal amounts
      wild-type receptor, the LDS mutations were found to confer a modest dominant
      negative effect. These results are discussed in relation to LDS and the related
      Marfan syndrome.

PMID- 22414222
TI  - Interkingdom adenosine signal reduces Pseudomonas aeruginosa pathogenicity.
AB  - Pseudomonas aeruginosa is becoming recognized as an important pathogen in the
      gastrointestinal (GI) tract. Here we demonstrate that adenosine, derived from
      hydrolysis of ATP from the eucaryotic host, is a potent interkingdom signal in
      the GI tract for this pathogen. The addition of adenosine nearly abolished P.
      aeruginosa biofilm formation and abolished swarming by preventing production of
      rhamnolipids. Since the adenosine metabolite inosine did not affect biofilm
      formation and since a mutant unable to metabolize adenosine behaved like the wild
      type strain, adenosine metabolism is not required to reduce pathogenicity.
      Adenosine also reduces production of the virulence factors pyocyanin, elastase,
      extracellular polysaccharide, siderophores and the Pseudomonas quinolone signal
      which led to reduced virulence with Caenorhabditis elegans. To provide insights
      into how adenosine reduces the virulence of P. aeruginosa, a whole-transcriptome
      analysis was conducted which revealed that adenosine addition represses genes
      similar to an iron-replete condition; however, adenosine did not directly bind
      Fur. Therefore, adenosine decreases P. aeruginosa pathogenicity as an
      interkingdom signal by causing genes related to iron acquisition to be repressed.

PMID- 22414223
TI  - Longitudinal study on morbidity and mortality in white veal calves in Belgium.
AB  - BACKGROUND: Mortality and morbidity are hardly documented in the white veal
      industry, despite high levels of antimicrobial drug use and resistance. The
      objective of the present study was to determine the causes and epidemiology of
      morbidity and mortality in dairy, beef and crossbred white veal production. A
      total of 5853 calves, housed in 15 production cohorts, were followed during one
      production cycle. Causes of mortality were determined by necropsy. Morbidity was
      daily recorded by the producers. RESULTS: The total mortality risk was 5,3% and
      was significantly higher in beef veal production compared to dairy or crossbreds.
      The main causes of mortality were pneumonia (1.3% of the calves at risk), ruminal
      disorders (0.7%), idiopathic peritonitis (0.5%), enterotoxaemia (0.5%) and
      enteritis (0.4%). Belgian Blue beef calves were more likely to die from
      pneumonia, enterotoxaemia and arthritis. Detection of bovine viral diarrhea virus
      at necropsy was associated with chronic pneumonia and pleuritis. Of the calves,
      25.4% was treated individually and the morbidity rate was 1.66 cases per 1000
      calf days at risk. The incidence rate of respiratory disease, diarrhea, arthritis
      and otitis was 0.95, 0.30, 0.11 and 0.07 cases per 1000 calf days at risk
      respectively. Morbidity peaked in the first three weeks after arrival and
      gradually declined towards the end of the production cycle. CONCLUSIONS: The
      present study provided insights into the causes and epidemiology of morbidity and
      mortality in white veal calves in Belgium, housed in the most frequent housing
      system in Europe. The necropsy findings, identified risk periods and differences
      between production systems can guide both veterinarians and producers towards the
      most profitable and ethical preventive and therapeutic protocols.

PMID- 22414224
TI  - Looking for interaction: quantitative measurement of research utilization by
      Dutch local health officials.
AB  - BACKGROUND: In the Netherlands, local authorities are required by law to develop
      local health memoranda, based on epidemiological analyses. The purpose of this
      study was to assess the actual use of these epidemiological reports by municipal
      health officials and associated factors that affect this use. METHOD: Based on a
      conceptual framework, we designed a questionnaire in which we operationalized
      instrumental, conceptual, and symbolic use, the interaction between researchers
      and local health officials, and four clusters of barriers in this interaction
      process. We conducted an internet survey among 155 Dutch local health officials
      representing 35% of all Dutch municipalities. By means of multiple regression
      analyses, we gained insight into the related factors for each of the three types
      of research utilization. RESULTS: The results show that local health officials
      use epidemiological research more often in a conceptual than an instrumental or
      symbolic way. This can be explained by the complexity of the local policy process
      which is often linked to policies in other areas, and the various policy actors
      involved. Conceptual use was statistically associated with a presentation given
      by the epidemiologist during the policy process, the presence of obstructions
      regarding the report's accessibility, and the local official's personal belief
      systems and interests originating from different professional values and
      responsibilities. Instrumental and symbolic use increased with the involvement of
      local officials in the research process. CONCLUSIONS: The results of this study
      provide a partial solution to understanding and influencing research utilization.
      The quantitative approach underpins earlier qualitative findings on this topic.
      The outcomes suggest that RPHS epidemiologists can use different strategies to
      improve research utilization. 'Blurring the boundaries', and the enhancement of
      interfaces between epidemiologists and local health officials, like direct
      interactions into each other's work processes, is expected to create better
      possibilities for optimizing research use.

PMID- 22414225
TI  - Comparison of pain on injection during induction of anaesthesia with alfaxalone
      and two formulations of propofol in dogs.
AB  - OBJECTIVE: To compare the incidence of pain during injection of three intravenous
      induction agents in dogs. STUDY DESIGN: Prospective, crossover, randomized,
      blinded, clinical study. ANIMALS: Thirty dogs requiring anaesthesia for
      radiotherapy. METHODS: Dogs were anaesthetized on three occasions at weekly
      intervals. An IV cephalic catheter was placed, flushed with saline and alfentanil
      0.01 mg kg(-1) and atropine 0.02 mg kg(-1) administered. After 30 seconds either:
      propofol lipid macroemulsion (Drug(P) ), propofol lipid-free microemulsion
      (Drug(PC) ) or alfaxalone (Drug(A)) was administered over 60 seconds. Each
      induction agent was administered once to each dog. Induction was recorded by
      video and reviewed by an assessor, unaware of treatment. Catheter placement
      (number of attempts, site, size and recent vein use) were recorded. Behavioural
      changes associated with pain or excitation, were recorded. Severity of pain on
      injection was recorded (mild, moderate or severe pain). Incidence of pain was
      analysed using logistic regression, excitation using McNemar's test (p < 0.05)
      and association of pain with induction agent and catheter placement using the
      Akaike Information Criterion (AIC). RESULTS: No dogs reacted to saline or
      Drug(A,) thus Drug(A) was excluded from analysis. Pain on injection occurred in
      six dogs (20%) with Drug(PC) and one dog (3.3%) with Drug(P). Pain was severe in
      four dogs with Drug(PC). Drug(P) resulted in a trend for reduced risk of pain
      compared to Drug(PC) (p = 0.076, odds ratio [confidence intervals] 0.14 [0.027
      0.86]). Both propofol formulations resulted in greater risk of excitation than
      Drug(A) (p = 0.0003, odds ratio 4.5 [1.86-10.90]). Induction agent was associated
      with pain, whilst catheter placement was not. One dog developed facial oedema and
      one other dog skin necrosis adjacent to the catheter site following Drug(PC.) The
      study was terminated early due to ethical concerns about the severity of
      reactions with Drug(PC). conclusions and clinical relevance: Drug(PC) was
      associated with clinically relevant moderate to severe pain behaviour whilst
      Drug(A) and Drug(P) were not.

PMID- 22414226
TI  - Immunolocalisation of 11beta-HSD-1 and -2, glucocorticoid receptor,
      mineralocorticoid receptor and Na+ K+-ATPase during the postnatal development of
      the rat epididymis.
AB  - Glucocorticoids have been implicated in male reproductive function and 11beta-HSD
      1 and -2, the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR),
      all of which are known to modulate glucocorticoid action, have been localised in
      the adult rat epididymis, but their developmental expression has not been
      investigated. Na(+)K(+)-ATPase activity, responsible for sodium transport, is
      induced by both mineralocorticoids and glucocorticoids in the kidney and colon,
      and has been localised in epididymal epithelium. This study examined the
      immunolocalisation of 11beta-HSD-1 and -2, GR, MR and Na(+)K(+)-ATPase in rat
      epididymal epithelium (n = 5) at postnatal days (pnd) 1, 7, 15, 28, 40, 60, 75
      and 104, and relative mRNA expression of 11beta-HSD-1 and -2, and GR at pre
      puberty (pnd 28) and post-puberty (pnd 75). 11beta-HSD-1, GR and MR were
      localised in the epididymal epithelium from pnd 1, and 11beta-HSD-2 and Na(+)K(+)
      ATPase reactivity from pnd 15. At pnd 28 there was maximal immunoreactivity for
      both the GR and MR and 11beta-HSD-1 and -2. 11beta-HSD-1 mRNA expression in the
      caput increased from pre- to post-puberty, whereas 11beta-HSD-2 mRNA expression
      fell over the same period (P < 0.01). GR mRNA expression was similar at pre- and
      post-puberty in both caput and cauda. Developmental changes in expression of
      11beta-HSD-1 and -2 suggest that overall exposure of the epididymis to
      glucocorticoids increases post-puberty, but cell-specific expression of the
      11beta-HSD enzymes still provides a capacity for intricate local control of
      glucocorticoid exposure.

PMID- 22414228
TI  - KCNQ1 gene polymorphisms are associated with the therapeutic efficacy of
      repaglinide in Chinese type 2 diabetic patients.
AB  - The present study evaluated the effects of KCNQ1 rs2237892 and rs2237895
      polymorphisms on repaglinide efficacy in Chinese patients with type 2 diabetes
      mellitus (T2DM). In all, 367 T2DM patients and 214 controls were genotyped. Forty
      of the T2DM patients were randomly selected to undergo 8 weeks repaglinide
      treatment. The frequency of the rs2237892 allele was lower in the T2DM patients
      than in the control group (P < 0.05). The frequency of the rs2237895 C allele was
      higher in T2DM patients than in healthy control subjects (P < 0.05). Diabetic
      patients with the rs2237892 risk C allele had lower fasting insulin levels (P <
      0.01) and homeostasis model assessment of insulin resistance (HOMA-IR; P < 0.01)
      values than carriers of the T allele. Diabetic patients with the rs2237895 risk C
      allele had higher fasting plasma glucose (P < 0.01), postprandial plasma glucose
      (PPG) levels (P < 0.01) and HOMA-IR values (P < 0.01) than those with the A
      allele. Following repaglinide treatment, those T2DM patients with the rs2237892 T
      allele and rs2237895 C allele were more likely to have a positive response to
      repaglinide in terms of PPG levels (P < 0.05) than T2DM patients with the
      rs2237892 CC and rs2237895 AA genotypes. In conclusion, KCNQ1 rs2237892 and
      rs2237895 polymorphisms were found to be associated with the therapeutic efficacy
      of repaglinide in Chinese T2DM patients.

PMID- 22414227
TI  - Epigenetic (de)regulation of adult hippocampal neurogenesis: implications for
      depression.
AB  - Adult neurogenesis represents a dynamic level of modulation upon the
      neuroplastic properties of the mature nervous system, that is essential to the
      homeostatic brain function. The adult neurogenic process comprises several
      sequential steps, all of which subjected to an assortment of cell-intrinsic and
      neurogenic-niche complex regulatory mechanisms. Among these, epigenetic
      regulation is now emerging as a crucial regulator of several neurogenesis steps.
      In particular, the active regulation of hippocampal neurogenesis and its
      repercussions in global hippocampal function are of special interest for the
      biomedical field, since imbalances at this level have been strongly related to
      the precipitation of several neuropsychyatric disorders, such as depression.
      Indeed, growing evidence supports that the detrimental effects on adult
      hippocampal neurogenesis, that have been associated with depression, might be
      epigenetically-mediated. Therefore, understanding the epigenetic regulation of
      the neurogenic process may provide a link between neurogenesis imbalances and the
      deterioration of the behavioural and cognitive domains frequently affected in
      depression, thus contributing to unravel the complex pathophysiology of this
      disorder.Here, we outline some of the major epigenetic mechanisms contributing to
      the regulation of hippocampal neurogenesis and discuss several lines of evidence
      supporting their involvement on the development of imbalances in the neurogenic
      process, often correlated to behavioural and cognitive deficits commonly observed
      in major depressive disorder.

PMID- 22414229
TI  - Anomalous bodily-self experiences among recreational ketamine users.
AB  - INTRODUCTION: Out-of-body experiences present a unique paradigm to investigate
      cognitive and neural mechanisms of bodily-self processes and their disorders.
      Previous work on out-of-body experiences associated with sleep paralysis
      supported a model in which illusory movement experiences reflect disrupted bodily
      self integration generating anomalous vestibular and motor sensations. Further
      disintegration and progression of the experience may then give rise to out-of
      body feelings, which in turn may instigate out-of-body autoscopy. METHODS: The
      current study assesses the disintegration model through analyses of out-of-body
      experiences reports from an online survey of individuals reporting recreational
      ketamine use (n=128) and cross-validation in a sample of nonketamine polydrug
      users (n=64). Path analyses using intensity and frequency measures of anomalous
      experiences assess the fit of seven competing models. RESULTS: The disintegration
      model (illusory movement -> out-of-body feelings -> out-of-body autoscopy)
      emerged as the best fitting model overall and results support full mediation of
      the relation between illusory movement experiences and out-of-body autoscopy by
      out-of-body feelings. Moreover, lifetime measures of ketamine use predicted the
      frequency of illusory movement experiences. CONCLUSIONS: The results corroborate
      this structural model of out-of-body phenomena and encourage a framework for
      future studies into aetiological mechanisms of out-of-body experiences to include
      neurochemical systems.

PMID- 22414230
TI  - Complexes of lanthanide nitrates with tri tert butylphosphine oxide.
AB  - Reaction of lanthanide nitrates with (t)Bu(3)PO (=L) lead to the isolation of
      complexes Ln(NO(3))(3)L(2).H(2)O.nEtOH (Ln = La (1), Nd(2)), Ln(NO(3))(3)L(2)
      .nEtOH (Sm(3), Eu(4)), and Ln(NO(3))(3)L(2) (Dy(5), Er(6), Lu(7)). These have
      been characterized by elemental analysis, infrared and NMR((1)H, (13)C and (31)P)
      spectroscopy and single-crystal X-ray diffraction. The structures show L to be
      positioned on opposite sides of the metal with the nitrates forming an equatorial
      band. When Ln = Dy, Er, and Lu two distinct molecules are present in the unit
      cell. A major isomer (70%) has a (P)O-Ln-O(P) angle of less than 180 degrees 
      with one of the nitrate ligands twisted out of the plane of the other nitrates
      while the lower abundance isomer is more symmetric with the (P)O-Ln-O(P) angle of
      180 degrees  and the nitrate ligands coplanar giving a hexagonal bipyramidal
      geometry. These isomers cannot be observed by variable temperature solution (31)P
      NMR measurements but are clearly seen in the solid-state NMR spectrum of the Lu
      complex. Variable temperature solid-state NMR indicates that the isomers do not
      interconvert at temperatures up to 100  degrees C. Attempts to prepare cationic
      species [Ln(NO(3))(2)L(3)](+)[PF(6)](-) have not been totally successful and led
      to the isolation of crystals of Lu(NO(3))(3)L(2) and Tb(NO(3))(3)L(2).CH(3)CN
      (8).

PMID- 22414231
TI  - Clinical Epigenetics is now a fully open access journal.

PMID- 22414232
TI  - Clinical features and outcomes of primary hepatic neuroendocrine carcinomas.
AB  - BACKGROUND AND AIM: Primary hepatic neuroendocrine carcinomas (PHNECs) are
      extremely rare, with only about 150 cases having been reported in the English
      language literature. Because of the rarity of PHNECs, its clinical features and
      treatment outcomes are not well understood. Here, we report our experiences with
      PHNECs. METHODS: We identified patients diagnosed with PHNEC and analyzed their
      demographics, baseline laboratory data, tumor characteristics, treatment
      modalities and outcomes. RESULTS: A total of 218 consecutive patients were
      identified with pathologically confirmed neuroendocrine carcinoma. Of these, 12
      patients were diagnosed with PHNECs; the median age was 66.5 years (range, 37 to
      80 years), and seven patients (58.3%) were male. Two patients who each had a
      single hepatic mass underwent curative surgical resection. One patient who was of
      inoperable status at the initial diagnosis because of multiple intrahepatic
      metastases showed a partial response after the ninth round of systemic
      chemotherapy and then underwent surgical resection. The median overall survival
      in the 12 patients was 16.5 months (range, 0.7 to 41.7 months). Three patients
      who underwent surgical treatment are alive without recurrence for 15.2 months,
      18.0 months, and 36.9 months, respectively. CONCLUSIONS: Primary hepatic
      neuroendocrine carcinoma should be considered as a possible differential
      diagnosis in the management of hepatic tumors. The liver can be the primary
      origin of neuroendocrine tumors, and if the tumors are diagnosed as primary
      hepatic neuroendocrine tumors, surgical resection must be considered for curative
      treatment.

PMID- 22414233
TI  - Postdialysis blood pressure rise predicts long-term outcomes in chronic
      hemodialysis patients: a four-year prospective observational cohort study.
AB  - BACKGROUND: The blood pressure (BP) of a proportion of chronic hemodialysis (HD)
      patients rises after HD. We investigated the influence of postdialysis BP rise on
      long-term outcomes. METHODS: A total of 115 prevalent HD patients were enrolled.
      Because of the fluctuating nature of predialysis and postdialysis BP, systolic BP
      (SBP) and diastolic BP before and after HD were recorded from 25 consecutive HD
      sessions during a 2-month period. Patients were followed for 4 years or until
      death or withdrawal. RESULTS: Kaplan-Meier estimates revealed that patients with
      average postdialysis SBP rise of more than 5 mmHg were at the highest risk of
      both cardiovascular and all-cause mortality as compared to those with an average
      postdialysis SBP change between -5 to 5 mmHg and those with an average
      postdialysis SBP drop of more than 5 mmHg. Furthermore, multivariate Cox
      regression analysis indicated that both postdialysis SBP rise of more than 5 mmHg
      (HR, 3.925 [95% CI, 1.410-10.846], p = 0.008) and high cardiothoracic (CT) ratio
      of more than 50% (HR, 7.560 [95% CI, 2.048-27.912], p = 0.002) independently
      predicted all-cause mortality. We also found that patients with an average
      postdialysis SBP rise were associated with subclinical volume overload, as
      evidenced by the significantly higher CT ratio (p = 0.008). CONCLUSIONS: A
      postdialysis SBP rise in HD patients independently predicted 4-year
      cardiovascular and all-cause mortality. Considering postdialysis SBP rise was
      associated with higher CT ratio, intensive evaluation of cardiac and volume
      status should be performed in patients with postdialysis SBP rise.

PMID- 22414234
TI  - The csgD mRNA as a hub for signal integration via multiple small RNAs.
AB  - The transcription factor CsgD governing the production of curli fimbriae and
      cellulose is a key player in the complex regulatory circuit that decides whether
      Escherichia coli form biofilms. The csgD gene itself is tightly controlled at the
      level of transcription by a large array of DNA-binding proteins, but what happens
      after transcription is less understood. In this issue of Molecular Microbiology,
      Jorgensen et al. (2012), Mika et al. (2012) and Thomason et al. (2012) report on
      small RNAs (McaS, RprA and GcvB) that together with the RNA-chaperone Hfq
      regulate the mRNAs of csgD and other biofilm genes, and illustrate the burgeoning
      concept that the 5' region of bacterial mRNA serves as a hub for sRNA-mediated
      signal integration at the post-transcriptional level.

PMID- 22414235
TI  - Modelling reproduction of Plutella xylostella L. (Lepidoptera: Plutellidae):
      climate change may modify pest incidence levels.
AB  - Temperature is considered to be an important abiotic factor influencing insect
      reproduction. Despite the importance of Plutella xylostella L. (Lepidoptera:
      Plutellidae) as a pest of brassicaceous crops worldwide, the effects of
      temperature on its reproduction are not well understood. We evaluated the effect
      of constant temperatures ranging from 10 to 32.5 degrees C on the reproduction of
      P. xylostella and developed an oviposition model for the species. The model
      combined temperature-dependent parameters of total fecundity, age-specific
      oviposition rate and age-specific survival. Additionally, we modelled population
      growth as a function of temperature. The estimated parameters allowed us to
      discuss the possible consequences of global warming on P. xylostella
      distribution. Temperature affected the length of pre-oviposition after adult
      emergence, oviposition period, longevity, total fecundity and egg viability. The
      model predicted that both daily egg production and length of oviposition period
      decreased at temperatures below 15 degrees C and above 25 degrees C. Population
      growth increased linearly with temperature in a range from 10 degrees C to 25
      degrees C; however, the model predicted a reduction in population growth at
      temperatures above 28.6 degrees C. Data suggested that temperature plays a
      critical role in P. xylostella reproduction, and subtle differences in average
      temperature could have an impact on its population growth. This is especially
      important in the context of global climate change, which in turn could alter the
      distribution and abundance of the pest in some regions of the world. 

PMID- 22414237
TI  - Efficient and high yield one-pot synthesis of cyclometalated platinum(II) beta
      diketonates at ambient temperature.
AB  - Cyclometalated Pt(II) beta-diketonates are widely used as efficient luminescent
      materials but are typically prepared at high temperatures in low yields using
      excess reagents. A one-pot synthesis of these complexes is described employing
      stoichiometric reagents and short reaction times at ambient temperature, giving
      yields of up to 94%. The method is applicable to a broad range of substrates
      including N^C, P^C, and C^C chelate Pt(II) complexes and different beta
      diketonate ligands.

PMID- 22414236
TI  - Negative life events and substance use moderate cognitive behavioral adolescent
      depression prevention intervention.
AB  - Investigate factors that amplify or mitigate the effects of an indicated
      cognitive behavioral (CB) depression prevention program for adolescents with
      elevated depressive symptoms. Using data from a randomized trial (Registration
      No. NCT00183417; n = 173) in which adolescents (M age=15.5, SD=1.2) were assigned
      to a brief cognitive behavioral prevention program or an educational brochure
      control condition, we tested whether elevated motivation to reduce depression and
      initial depressive symptom severity amplified intervention effects and whether
      negative life events, social support deficits, and substance use attenuated
      intervention effects. Hierarchical linear modeling (HLM) indicated differential
      intervention effects for two of the five examined variables: negative life events
      and substance use. For adolescents at low and medium levels of substance use or
      negative life events, the CB intervention produced declines in depressive
      symptoms relative to controls. However, at high levels of substance use or
      negative life events, the CB intervention did not significantly reduce depressive
      symptoms in comparison to controls. Results imply that high-risk adolescents with
      either high rates of major life stress or initial substance use may require
      specialized depression prevention efforts.

PMID- 22414238
TI  - Morphological evidence that pentagastrin regulates secretion in the human parotid
      gland.
AB  - Salivary secretion is principally regulated by autonomic nerves. However, recent
      evidence from in vivo animal experiments suggests that gastrointestinal peptide
      hormones can also influence saliva production. The aim of the present study was
      to define the secretagogue activity of the gastrin-analogue pentagastrin in human
      salivary glands. For this purpose, parotid tissues were exposed to pentagastrin
      in vitro. Morphological techniques were used to evaluate modifications to serous
      acinar cells associated with secretion. Using a variant of the osmium maceration
      method, high resolution scanning electron microscopy allowed assessment of the
      morphology of the cytoplasmic aspect of the plasmalemma to demonstrate secretory
      activity. To quantify responses to pentagastrin, we recorded morphometric data on
      microvilli, microbuds, and protrusions. Dose-dependent morphological changes were
      observed, whereas protein concentration increased in the incubate. The use of
      selective receptor antagonists showed pentagastrin to act principally via
      cholecystokinin-A receptors. The morphological responses observed following
      exposure to pentagastrin differed from those elicited following exposure to the
      pan-muscarinic agonist carbachol. This study provides the first demonstration of
      a direct secretory action of gastrointestinal peptides on salivary glands in
      humans.

PMID- 22414239
TI  - Magnetic properties of hexanuclear lanthanide(III) clusters incorporating a
      central MU6-carbonate ligand derived from atmospheric CO2 fixation.
AB  - Three isostructural hexanuclear lanthanide(III) clusters are reported (Ln(III) =
      Gd, Tb, and Dy). The metallic core of each complex displays an unusual
      arrangement of ions, which is stabilized by a MU(6)-carbonate ligand. Magnetic
      studies show that the Ln(III) ions in each compound are weakly exchange coupled,
      with the Tb and Dy analogues displaying single-molecule-magnet behavior.

PMID- 22414240
TI  - Diet quality and mental health in subsequent years among Canadian youth.
AB  - OBJECTIVE: To examine the association between diet quality and the diagnosis of
      an internalizing disorder in children and adolescents. DESIGN: A prospective
      study examining the relationship between diet quality and mental health. FFQ
      responses of 3757 children were used to calculate a composite score for diet
      quality and its four components: variety, adequacy, moderation and balance.
      Physicians' diagnoses on internalizing disorders were obtained by linking the
      children's dietary information to administrative health data. Negative binomial
      regression models were used to examine the association between diet quality and
      diagnosis of an internalizing disorder. SETTING: The Canadian province of Nova
      Scotia. SUBJECTS: A provincially representative sample of grade 5 students (age
      10-11 years). RESULTS: Diet quality was not found to be associated with
      internalizing disorder in a statistically significant manner (incidence rate
      ratio = 1.09; 95 % CI 0.73, 1.63). However, relative to children with little
      variety in their diets, children with greater variety in their diet had
      statistically significant lower rates of internalizing disorder in subsequent
      years (incidence rate ratio = 0.45; 95 % CI 0.25, 0.82). CONCLUSIONS: These
      findings suggest the importance of variety in children's diet and opportunities
      in the prevention of adolescent depression and anxiety.

PMID- 22414241
TI  - Cytotoxic T-lymphocyte associated antigen-4 gene polymorphisms and primary
      biliary cirrhosis: a systematic review.
AB  - BACKGROUND AND AIM: The cytotoxic T-lymphocyte antigen 4 (CTLA4) is an inhibitory
      receptor expressed on activated and regulatory T lymphocytes. Polymorphisms could
      have remarkable effects on susceptibility to autoimmunity. However, the
      associations between CTLA-4 polymorphisms and primary biliary cirrhosis (PBC)
      remain ambiguous. The aim of this meta-analysis is to determine more precise
      estimations of the relationship. METHODS: From literature retrieval from PubMed,
      Web of Science, Science Direct, and the Chinese National Knowledge Infrastructure
      (CNKI) Database, the publications on the associations between rs231775,
      rs3087243, rs5742909, rs231725 and rs11571317 polymorphisms of CTLA4 and PBC
      through June 2011 were collected. Odds ratios (OR) with 95% confidence intervals
      (95% CI) were calculated in fixed or random model, I(2) was calculated to examine
      heterogeneity, and funnel plots were plotted to examine small study effects with
      Revman 5.1 and Stata 11. RESULTS: Overall, a significantly increased risk was
      found for G versus A allele for rs231775 (OR = 1.28, 95% CI = 1.17-1.41). For
      rs3087243, a significant association was found for AA versus GG genotype (OR =
      0.66; 95% CI = 0.55-0.80). When subgroup analysis by ethnicity was performed, the
      same association was only found in Caucasians. For rs231725, the OR values (95%
      CI) for GG versus AA, GA versus AA and G versus A allele were 0.52 (0.40-0.68),
      0.74 (0.60-0.92) and 0.73 (0.61-0.88). No significant associations were found for
      other polymorphisms. CONCLUSION: The G allele of rs231775 is a risk factor for
      PBC, while AA genotype of rs3087243 and GG, GA and G allele of rs231725 show
      negative associations with PBC.

PMID- 22414242
TI  - A universal method for the detection and identification of Aphidiinae parasitoids
      within their aphid hosts.
AB  - Molecular methods are increasingly used to detect and identify parasites in their
      hosts. However, existing methods are generally not appropriate for studying
      complex host-parasite interactions because they require prior knowledge of
      species composition. DNA barcoding is a molecular method that allows identifying
      species using DNA sequences as an identification key. We used DNA amplification
      with primers common to aphid parasitoids and sequencing of the amplified fragment
      to detect and identify parasitoids in their hosts, without prior knowledge on the
      species potentially present. To implement this approach, we developed a method
      based on 16S rRNA mitochondrial gene and LWRh nuclear gene. First, we designed
      two primer pairs specific to Aphidiinae (Hymenoptera), the main group of aphid
      parasitoids. Second, we tested whether the amplified regions could correctly
      identify Aphidiinae species and found that 61 species were accurately identified
      of 75 tested. We then determined the ability of each primer pair to detect
      immature parasitoids inside their aphid host. Detection was earlier for 16S than
      for LWRh, with parasitoids detected, respectively, 24 and 48 h after egg
      injection. Finally, we applied this method to assess parasitism rate in field
      populations of several aphid species. The interest of this tool for analysing
      aphid-parasitoid food webs is discussed.

PMID- 22414243
TI  - Rapid detection of common mutations of the FGFR3 gene causing thanatophoric
      dysplasia type I: two case reports.
AB  - Thanatophoric dysplasia (TD) is a relatively common lethal skeletal dysplasia.
      These malformations result from the mutations in fibroblast growth factor
      receptor 3 (FGFR3) gene, which is located on the short arm of chromosome 4.
      Accurate diagnosis of fetal TD is important for patient counseling and to plan
      the management. A definite diagnosis can be established by molecular genetic
      analysis to find out the abnormal mutations in the FGFR3 gene. We reported on two
      cases of TD type I found by prenatal ultrasound and confirmed by molecular
      analysis of FGFR3 gene using high-resolution melting analysis.

PMID- 22414245
TI  - Influence of fentanyl on intra-abdominal pressure during laparoscopy in dogs.
AB  - OBJECTIVE: To evaluate the influence of fentanyl on intra-abdominal pressures in
      spontaneously breathing dogs during capnoperitoneum. STUDY DESIGN: Prospective
      clinical study. ANIMALS: Eleven healthy client-owned and five healthy
      experimental dogs undergoing laparoscopy. METHODS: Dogs were premedicated with
      acepromazine (0.03 mg kg(-1) IV) and carprofen (4 mg kg(-1) IV). Anaesthesia was
      induced with propofol and maintained with isoflurane in oxygen. The abdomen was
      insufflated with CO(2) (11-16 cm H(2) O). Intra-abdominal pressures were measured
      with a transducer. Respiratory variables were measured with a spirometry sensor
      and side-stream capnography. Following preparation, fentanyl (1 MUg kg(-1) ) was
      injected over 30 seconds IV. Data were recorded 5 minutes before, during and 5
      minutes after treatment. The following time points were selected for statistical
      analysis (anova, p < 0.05): -160, -140, -120, -100, -80, -60, -40, -20, 0, 30,
      50, 70, 90, 110, 130 and 150 seconds after the start of fentanyl injection.
      RESULTS: Intra-abdominal pressure increased during inspiration in 15 dogs but
      decreased in one dog. Fentanyl treatment did not alter these patterns. Peak
      inspiratory and end-expiratory intra-abdominal pressures continuously decreased
      over time during the whole experiment and fentanyl exaggerated the decrease in
      inspiratory pressures but did not affect the rate of decrease in expiratory
      pressures. Differences between intra-abdominal pressures were stable before, but
      decreased after fentanyl administration from 4.1 +/- 1.4 to 3.3 +/- 1.2 cm H(2) O
      (at 0 and 150 seconds time points). End-tidal CO(2) partial pressures increased
      from 6.0 +/- 0.8 to 6.6 +/- 0.9 kPa, respiratory rate decreased from 10.8 +/- 2.6
      to 7.8 +/- 2.2 breaths per minute and tidal volume decreased from 13.7 +/- 4.4 to
      12.4 +/- 2.9 mL kg(-1) after fentanyl but these variables did not change before
      fentanyl treatment. Airway pressures did not change. CONCLUSIONS AND CLINICAL
      RELEVANCE: Fentanyl did not increase intra-abdominal pressures in dogs.

PMID- 22414244
TI  - Addition of bevacizumab to first-line chemotherapy in advanced colorectal cancer:
      a systematic review and meta-analysis, with emphasis on chemotherapy subgroups.
AB  - BACKGROUND: Bevacizumab has an important role in first-line treatment of
      metastatic colorectal cancer. However, clinical trials studying its effect have
      involved distinct chemotherapy regimens with divergent results. The aim of this
      meta-analysis is to gather current data and evaluate not only the efficacy of
      bevacizumab, but also the impact of divergent backbone regimens. METHODS: A wide
      search of randomized clinical trials using bevacizumab in first-line metastatic
      colorectal cancer was performed in Embase, MEDLINE, LILACS and Cochrane
      databases. Meeting presentations and abstracts were also investigated. The
      resulting data were examined and included in the meta-analysis according to the
      type of regimen. RESULTS: Six trials, totaling 3060 patients, were analyzed.
      There was an advantage to using bevacizumab for overall survival (OS) and
      progression-free survival (PFS) (HR = 0.84; CI: 0.77-0.91; P < 0.00001 and HR =
      0.72; CI: 0.66-0.78; P < 0.00001, respectively). However, heterogeneity of
      results was very high for both outcomes, and subgroup analyses supported the OS
      advantage with bevacizumab restricted to irinotecan-based regimens. Infusional
      fluorouracil subsets involved a minor proportion, and did not demonstrate
      statistical benefit in PFS or OS. Regarding toxicity, higher rates of grades 3-4
      hypertension, bleeding, thromboembolic events and proteinuria were uniformly
      observed with bevacizumab, leading to increased treatment interruptions (HR =
      1.47; P = 0.0004). CONCLUSIONS: Bevacizumab has efficacy in first-line treatment
      of advanced colorectal cancer, but the current data are insufficient to support
      efficacy in all regimens, especially infusional fluorouracil regimens, like
      FOLFIRI and FOLFOX.

PMID- 22414246
TI  - Determinants of successful clinical networks: the conceptual framework and study
      protocol.
AB  - BACKGROUND: Clinical networks are increasingly being viewed as an important
      strategy for increasing evidence-based practice and improving models of care, but
      success is variable and characteristics of networks with high impact are
      uncertain. This study takes advantage of the variability in the functioning and
      outcomes of networks supported by the Australian New South Wales (NSW) Agency for
      Clinical Innovation's non-mandatory model of clinical networks to investigate the
      factors that contribute to the success of clinical networks. METHODS/DESIGN: The
      objective of this retrospective study is to examine the association between
      external support, organisational and program factors, and indicators of success
      among 19 clinical networks over a three-year period (2006-2008). The outcomes
      (health impact, system impact, programs implemented, engagement, user perception,
      and financial leverage) and explanatory factors will be collected using a web
      based survey, interviews, and record review. An independent expert panel will
      provide judgements about the impact or extent of each network's initiatives on
      health and system impacts. The ratings of the expert panel will be the outcome
      used in multivariable analyses. Following the rating of network success, a
      qualitative study will be conducted to provide a more in-depth examination of the
      most successful networks. DISCUSSION: This is the first study to combine
      quantitative and qualitative methods to examine the factors that contribute to
      the success of clinical networks and, more generally, is the largest study of
      clinical networks undertaken. The adaptation of expert panel methods to rate the
      impacts of networks is the methodological innovation of this study. The proposed
      project will identify the conditions that should be established or encouraged by
      agencies developing clinical networks and will be of immediate use in forming
      strategies and programs to maximise the effectiveness of such networks.

PMID- 22414247
TI  - Analysis of hypermethylation and expression profiles of APC and ATM genes in
      patients with oral squamous cell carcinoma.
AB  - BACKGROUND: Adenomatous polyposis coli (APC) and Ataxia-telangiectasia-mutated
      (ATM) gene products have an important role in cell cycle control and maintenance
      of genomic stability. Our aim was to analyze ATM and APC methylation and its
      relationship with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS:
      Eighty-four OSCC tissues that have been fixed in paraffin along with 57 control
      oral samples have been used for analyzing promoter methylation of ATM and APC
      genes by Methylation Specific Polymerase Chain Reaction (MS-PCR). In addition, 10
      cases of OSCC and the same of matched controls were examined for estimating
      expression of the above mentioned genes using Real-Time Reverse-Transcription
      PCR. RESULTS: Observed promoter methylations were 71.42% and 87.71% for the APC
      gene and 88.09% and 77.19% for the ATM gene in cases and controls, respectively.
      Analysis of these data showed that promoter methylation at APC was significantly
      different in cases compared to healthy controls (p = 0.01), but no difference was
      detected for the ATM gene. Furthermore, the mRNA expression levels did not differ
      statistically between cases and controls for both ATM (cases = 9, controls = 10)
      and APC (cases = 11, controls = 10) genes. CONCLUSIONS: Our results, for the
      first time, provide methylation profiles of ATM and APC genes in a sample of
      patients with OSCC in a southeast Iranian population. The present data support
      related evidence of APC methylation effect on OSCC development.

PMID- 22414248
TI  - Brain base arteries: pattern and variation in the European otter (Lutra lutra).
AB  - The pattern and variation of the brain base arteries were investigated in 30
      specimens of European otter. It was found that the vascular pattern in this
      species is similar to the vascular pattern found in other Carnivora. A very well
      developed basilar artery, which was formed as a result of the anastomosis of
      equally well-developed vertebral arteries and the ventral spinal artery, was
      demonstrated to be characteristic of the species. Most of the variation in the
      pattern of origin concerned the origin of the middle cerebral arteries and
      labyrinthine arteries. In a single individual, a double middle cerebral artery
      was observed. Overall, the specimens demonstrated a clear regularity in the
      pattern of vessels in the base of the brain and a small range of variation.

PMID- 22414249
TI  - Twofold light and magnetic responsive behavior in nanoparticle-lyotropic liquid
      crystal systems.
AB  - We demonstrate the dual magnetic and light responsive nature of hybrid mesophases
      constituted by Fe(3)O(4) nanoparticles dispersed in lipid-based lyotropic liquid
      crystals (LC). When subjected to an external magnetic field in the mesophase
      isotropic state, the nanoparticles aggregate and orient along the magnetic field
      direction, and upon cooling the system through the disorder-order transition the
      aggregates drive the orientation of the mesophase via heterogeneous nucleation;
      furthermore, order-disorder transitions in the lipidic mesophase can be triggered
      by Fe(3)O(4)-induced photothermal effect under visible light exposure. Both the
      orientational order and the photothermal effect of the hybrid mesophase can be
      tuned by the nanoparticle content, offering a general route for controlled
      assembly of complex fluids with combined magnetic and light responsiveness.

PMID- 22414250
TI  - Current status and future perspectives of leukocytapheresis for inflammatory
      bowel disease.
AB  - Ulcerative colitis (UC) and Crohn's disease (CD) comprise the idiopathic
      inflammatory bowel diseases (IBD) of the gut. The etiology of IBD is poorly
      understood, but an autoimmune disturbance has been suggested to play an important
      role in this incurable disease. Extracorporeal leukocytapheresis (CAP) is an
      additional adjunct for IBD patients refractory to other conventional therapies,
      including steroids. The primary aim of CAP should be to suppress such unwanted
      immunological response by removing circulating inflammatory cells from the blood
      stream. The first decade has been passed since CAP was approved by Japanese
      social health insurance policy. It is therefore now an appropriate opportunity to
      upgrade and summarize our current understandings and/or future perspectives of
      this unique non-pharmacological and non-surgical strategy for IBD patients.
      According to several clinical and basic research reports, an early introduction
      of CAP should produce higher efficacy as compared with CAP applied sometime after
      a clinical relapse. Likewise, CAP therapy adjusted to patients' body-weight as
      well as two treatment sessions per week (intensive regimen) should benefit the
      efficacy rate. The etiology of IBD is not fully elucidated yet. As a result, the
      major therapeutic strategies in the Western world have been immunosuppressive
      therapy, including biologics. CAP is an unusual treatment modality for IBD
      because it seems to have both effectiveness and safety, which should generally be
      balanced in this type of illness. We now have to develop future strategies with
      and without combining biologics to improve the quality of life of IBD patients.

PMID- 22414252
TI  - Carbocyclization cascades of allyl ketenimines via aza-Claisen rearrangements of
      N-phosphoryl-N-allyl-ynamides.
AB  - A series of carbocyclization cascades of allyl ketenimines initiated through a
      thermal aza-Claisen rearrangement of N-phosphoryl-N-allyl ynamides is described.
      Interceptions of the cationic intermediate via Meerwein-Wagner rearrangements and
      polyene-type cyclizations en route to fused bi- and tricyclic frameworks are
      featured.

PMID- 22414251
TI  - Incremental evolution of the neural crest, neural crest cells and neural crest
      derived skeletal tissues.
AB  - Urochordates (ascidians) have recently supplanted cephalochordates (amphioxus) as
      the extant sister taxon of vertebrates. Given that urochordates possess migratory
      cells that have been classified as 'neural crest-like'- and that cephalochordates
      lack such cells--this phylogenetic hypothesis may have significant implications
      with respect to the origin of the neural crest and neural crest-derived skeletal
      tissues in vertebrates. We present an overview of the genes and gene regulatory
      network associated with specification of the neural crest in vertebrates. We then
      use these molecular data--alongside cell behaviour, cell fate and embryonic
      context--to assess putative antecedents (latent homologues) of the neural crest
      or neural crest cells in ascidians and cephalochordates. Ascidian migratory
      mesenchymal cells--non-pigment-forming trunk lateral line cells and pigment
      forming 'neural crest-like cells' (NCLC)--are unlikely latent neural crest cell
      homologues. Rather, Snail-expressing cells at the neural plate of border of
      urochordates and cephalochordates likely represent the extent of neural crest
      elaboration in non-vertebrate chordates. We also review evidence for the
      evolutionary origin of two neural crest-derived skeletal tissues--cartilage and
      dentine. Dentine is a bona fide vertebrate novelty, and dentine-secreting
      odontoblasts represent a cell type that is exclusively derived from the neural
      crest. Cartilage, on the other hand, likely has a much deeper origin within the
      Metazoa. The mesodermally derived cellular cartilages of some protostome
      invertebrates are much more similar to vertebrate cartilage than is the acellular
      'cartilage-like' tissue in cephalochordate pharyngeal arches. Cartilage,
      therefore, is not a vertebrate novelty, and a well-developed chondrogenic program
      was most likely co-opted from mesoderm to the neural crest along the vertebrate
      stem. We conclude that the neural crest is a vertebrate novelty, but that neural
      crest cells and their derivatives evolved and diversified in a step-wise fashion-
      first by elaboration of neural plate border cells, then by the innovation or co
      option of new or ancient metazoan cell fates.

PMID- 22414253
TI  - Carbonyl amine/Schiff base ligands in manganese complexes: theoretical study on
      the mechanism, capability of NO release.
AB  - A compound having the capability of releasing NO upon exposure to visible or near
      infrared (vis or NIR) light could be a potential candidate for photodynamic
      therapy (PDT), which is significant for humans. Here, we investigated a series of
      Mn(II) complexes (a-d) based on density functional theory (DFT) to illuminate the
      mechanism of their behavior of releasing NO. Their structural, spectroscopic, and
      photodissociable properties were calculated by quantum theoretical methods to
      give a detailed and warranted explanation of the performance of releasing NO. The
      results indicate that, for a-d, releasing NO was attributed to the electron
      transfer from d(yz)/d(xz)(Mn) orbitals to pi*(NO) orbitals at the second excited
      triplet state (T(2)). Importantly, we confirmed the finding in the experiment
      that d could release NO upon exposure to the NIR region and, thus, may be a best
      candidate for PDT in a-d. Therefore, to take d for example, the analyses of the
      potential energy curves (PECs) of difference states and electron density
      difference between the T(2) and the ground state (S(0)) were performed to further
      provide evidence of ligand dissociation and release of NO at the T(2) state.
      Finally, we hope that our discussion can provide assistance to understand the
      behavior of the release of NO and design novel photodissociable transition metal
      nitrosyls for PDT applications.

PMID- 22414254
TI  - Impact of DNA methylation on trophoblast function.
AB  - The influence of epigenetics is evident in many fields of medicine today. This
      is also true in placentology, where versatile epigenetic mechanisms that regulate
      expression of genes have shown to have important influence on trophoblast
      implantation and placentation. Such gene regulation can be established in
      different ways and on different molecular levels, the most common being the DNA
      methylation. DNA methylation has been shown today as an important predictive
      component in assessing clinical prognosis of certain malignant tumors; in
      addition, it opens up new possibilities for non-invasive prenatal diagnosis
      utilizing cell-free fetal DNA methods. By using a well known demethylating agent
      5-azacytidine in pregnant rat model, we have been able to change gene expression
      and, consequently, the processes of trophoblast differentiation and placental
      development. In this review, we describe how changes in gene methylation effect
      trophoblast development and placentation and offer our perspective on use of
      trophoblast epigenetic research for better understanding of not only placenta
      development but cancer cell growth and invasion as well.

PMID- 22414255
TI  - Temporal trends and anaemia-associated factors in 6- to 59-month-old children in
      Northeast Brazil.
AB  - OBJECTIVE: To analyse the trends and factors associated with anaemia in 6- to 59
      month-old children in Northeast Brazil. DESIGN: Cross-sectional study assessed
      information from the second and third Pernambuco State Health and Nutrition
      Surveys carried out in 1997 and 2006. A multiple regression analysis was
      performed from a conceptual model addressing biological and socio-economic
      factors, housing and sanitation conditions, maternal factors, health care and
      nutrition, consumption, morbidity and nutritional status. Poisson's regression
      with robust variance was used. SETTING: Pernambuco, Brazil. SUBJECTS: A total of
      777 and 993 children, respectively, in the second and third Pernambuco State
      Health and Nutrition Surveys. RESULTS: The prevalence of anaemia (Hb < 11 g/dl)
      decreased by 19.3 % (40.9 % down to 33.0 %) between surveys. Maternal education
      level (less than 8 years in school), households ranked in the lowest
      environmental index tertile and children between 6 and 23 months of age were the
      variables common to the final models in the surveys of 1997 and 2006. Elements
      like living in rural areas, household income less than two minimum official wages
      and low birth weight were still present in the final model of the 1997 survey.
      Households ranked in the lowest economic index tertile were associated with
      anaemia in the model of the 2006 survey. CONCLUSIONS: The study results are quite
      encouraging from the perspective of reducing the prevalence of anaemia. Maternal
      education level, environmental conditions and child age were determinant factors
      in both surveys, and economic factors were determinant in 2006.

PMID- 22414256
TI  - Biomimetic droplets for artificial engagement of living cell surface receptors:
      the specific case of the T-cell.
AB  - Liquid colloids, in the form of droplets grafted with specific biomolecules, are
      emerging as potential biomimetic systems. Here we show for the first time the
      possibility of forming hybrid conjugates between an advanced living cell model,
      the T-cell of the Jurkat cell line, and a specifically grafted droplet. Using T
      cells expressing a fluorescent chimeric protein associated with the TCR/CD3
      complex and fluorescent ligand-grafted droplets, we demonstrate formation of an
      interfacial contact concentrated in linking molecules, the morphology and
      dynamics of which strongly depend on the targeted receptor. The sequence of
      events ranges from the initial concentration of molecules following an unbound
      molecule gradient to active actin-driven spreading and fragmentation of the
      contact, ending with droplet internalization. We observed synchronized
      colocalization of receptors and ligands driven by cell dynamics and closely
      mirrored by the droplet interface. Using intracellular calcium probe Fura-2, we
      also showed that the cell/droplet interaction can trigger the T-cell signaling
      cascade. By examining molecular dynamics using FRAP measurements, we observed a
      nearly frozen cell droplet joining interface. Taken together, our results point
      to liquid colloids as promising new tools both for probing cell surface
      interactions and receptor dynamics and for manipulating biological cell
      functions.

PMID- 22414257
TI  - Proinflammatory and anti-inflammatory cytokines in gingival crevicular fluid and
      serum of patients with rheumatoid arthritis and patients with chronic
      periodontitis.
AB  - BACKGROUND: The aim of this study is to evaluate proinflammatory and anti
      inflammatory cytokine levels in gingival crevicular fluid (GCF) and serum of
      rheumatoid arthritis (RA) and chronic periodontitis (CP) patients to assess
      whether cytokine profiles distinguish patients with RA and patients with CP while
      using healthy patients as background controls. METHODS: A total of 49 patients,
      17 patients with RA (three males and 14 females; mean age: 47.82 +/- 10.74
      years), 16 patients with CP (10 males and six females; mean age: 44.00 +/- 7.00
      years), and 16 controls (eight males and eight females; mean age: 28.06 +/- 6.18
      years) were enrolled. Patients with RA were under the supervision of
      rheumatologists; 15 of the patients with RA were being treated with methotrexate
      sulfasalazine combined therapy, and two of the patients were being treated with
      leflunomid therapy. Periodontal parameters (plaque index, gingival index, probing
      depth, and clinical attachment level) were recorded. Interleukin (IL)-1beta, IL
      4, IL-10, and tumor necrosis factor-alpha (TNF-alpha) were determined in GCF and
      IL-1beta and IL-10 in serum by enzyme-linked immunosorbent assay. RESULTS: There
      were significant differences found among RA, CP, and control groups for all
      periodontal parameters (P <0.05). The total amount and concentration of GCF IL-1
      beta, IL-4, IL-10, and TNF-alpha were similar in RA and CP patients (P >0.05).
      Although the total amount and concentration of serum IL-10 was not significantly
      different among the groups (P >0.05), serum IL-1beta was significantly lower in
      the RA group compared to CP patients and controls and was higher in GCF of the RA
      group compared to the CP group. CONCLUSIONS: Although clinical periodontal
      disease parameters indicated more severe periodontal disease in CP compared to RA
      patients, immunologic evaluation did not reveal consistent results regarding
      proinflammatory and anti-inflammatory cytokine levels. This might be a result of
      the use of non-steroidal anti-inflammatory drugs and rheumatoid agents by
      patients with RA.

PMID- 22414258
TI  - Alveolar bone loss associated with age-related macular degeneration in males.
AB  - BACKGROUND: The aim of this study is to examine the relationship of selected
      systemic and oral health parameters and the salivary presence of six periodontal
      pathogens to age-related macular degeneration (AMD). METHODS: The present cross
      sectional study includes data on 1,751 individuals (>=30 years old). General
      health information was obtained by questionnaires and interviews, including self
      reported diagnosis of AMD, as well as by the general and oral health examination,
      including panoramic radiography and laboratory analyses. Fifty-four individuals
      with degenerative fundus changes formed the AMD group, and the other 1,697 formed
      the non-AMD group. Pearson chi(2) and analysis of variance tests were used for
      comparisons of categorical parameters and continuous parameters between the
      participant groups, respectively. A logistic regression analysis was performed to
      study the association of AMD with alveolar bone loss and the number of teeth by
      controlling for age, diabetic status, systolic blood pressure, education, and
      smoking, and also for the carriage of salivary bacteria. RESULTS: Advanced age,
      systolic blood pressure, and diabetes were associated with AMD (P <0.001),
      whereas the carriage rates of the examined periodontal pathogens were not. In the
      whole study population, the participants with AMD had fewer teeth (P <0.001) and
      more alveolar bone loss (P = 0.004) compared with non-AMD participants. In a
      logistic regression model adjusted for age, smoking, and diabetes, alveolar bone
      loss was associated with AMD in males with an odds ratio of 4.3 (95% confidence
      interval = 1.3 to 14.6, P = 0.013). CONCLUSION: In this population-based health
      survey, alveolar bone loss is independently associated with AMD in males.

PMID- 22414259
TI  - Nano-sized calcium phosphate particles for periodontal gene therapy.
AB  - BACKGROUND: Growth factors such as platelet-derived growth factor (PDGF) have
      significantly enhanced periodontal therapy outcomes with a high degree of
      variability, mostly due to the lack of continual supply for a required period of
      time. One method to overcome this barrier is gene therapy. The aim of this in
      vitro study is to evaluate PDGF-B gene delivery in fibroblasts using nano-sized
      calcium phosphate particles (NCaPP) as vectors. METHODS: NCaPP incorporating
      green fluorescent protein (NCaPP-GFP) and PDGF-B (NCaPP-PDGF-B) plasmids were
      synthesized using an established precipitation system and characterized using
      transmission electron microscopy and 1.2% agarose gel electrophoresis.
      Biocompatibility and transfection of the nanoplexes in fibroblasts were evaluated
      using cytotoxicity assay and florescence microscopy, respectively. Polymerase
      chain reaction and enzyme-linked immunosorbent assay were performed to evaluate
      PDGF-B transfection after different time points of treatments, and the
      functionality of PDGF-B transfection was evaluated using the cell proliferation
      assay. RESULTS: Synthesized NCaPP nanoplexes incorporating the genes of GFP and
      PDGF-B were spherical in shape and measured about 30 to 50 nm in diameter. Gel
      electrophoresis confirmed DNA incorporation and stability within the nanoplexes,
      and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium reagent assay demonstrated their biocompatibility in fibroblasts. In
      vitro transfection studies revealed a higher and longer lasting transfection
      after NCaPP-PDGF-B treatment, which lasted up to 96 hours. Significantly enhanced
      fibroblast proliferation observed in NCaPP-PDGF-B-treated cells confirmed the
      functionality of these nanoplexes. CONCLUSION: NCaPP demonstrated higher levels
      of biocompatibility and efficiently transfected PDGF plasmids into fibroblasts
      under described in vitro conditions.

PMID- 22414260
TI  - The lifetime direct cost of periodontal treatment: a case study from a Norwegian
      specialist practice.
AB  - BACKGROUND: Successful periodontal treatment requires a commitment to regular
      lifelong maintenance and may be perceived by patients to be costly. This study
      calculates the total lifetime cost of periodontal treatment in the setting of a
      specialist periodontal practice and investigates the cost implications of
      choosing not to proceed with such treatment. METHODS: Data from patients treated
      in a specialist practice in Norway were used to calculate the total lifetime cost
      of periodontal treatment that included baseline periodontal treatment, regular
      maintenance, retreatment, and replacing teeth lost during maintenance.
      Incremental costs for alternative strategies based on opting to forego
      periodontal treatment or maintenance and to replace any teeth lost with either
      bridgework or implants were calculated. RESULTS: Patients who completed baseline
      periodontal treatment but did not have any additional maintenance or retreatment
      could replace only three teeth with bridgework or two teeth with implants before
      the cost of replacing additional teeth would exceed the cost of lifetime
      periodontal treatment. Patients who did not have any periodontal treatment could
      replace <= 4 teeth with bridgework or implants before a replacement strategy
      became more expensive. CONCLUSIONS: Within the limits of the assumptions made,
      periodontal treatment in a Norwegian specialist periodontal practice is cost
      effective when compared to an approach that relies on opting to replace teeth
      lost as a result of progressive periodontitis with fixed restorations. In
      particular, patients who have initial comprehensive periodontal treatment but do
      not subsequently comply with maintenance could, on average, replace <= 3 teeth
      with bridgework or two teeth with implants before this approach would exceed the
      direct cost of lifetime periodontal treatment in the setting of the specialist
      practice studied.

PMID- 22414261
TI  - Exfoliative cytology and titanium dental implants: a pilot study.
AB  - BACKGROUND: Oral exfoliative cytology is a diagnostic method that involves the
      study of cells exfoliated from the oral mucosa. Ions/particles released from
      metallic implants can remain in the peri-implant milieu. The aim of the present
      study is to assess the presence of metal particles in cells exfoliated from peri
      implant oral mucosa around titanium dental implants. METHODS: The study comprised
      30 patients carrying titanium dental implants, who had neither a metallic
      prosthesis nor metal restorations in neighboring teeth. Individuals undergoing
      orthodontic therapy and those who had oral piercing were also excluded from the
      study. The study sample included patients with and without peri-implantitis.
      Cytologic samples of the peri-implant area were collected. Samples of the
      marginal gingiva on the contralateral side of the implant were taken from the
      same individuals to serve as control. Cytologic analysis was performed using
      light microscopy. Titanium concentration was determined using inductively coupled
      plasma-mass spectrophotometry. RESULTS: Metal-like particles were observed inside
      and outside epithelial cells and macrophages in cytologic smears of peri-implant
      mucosa of both patients with and without peri-implantitis. No particles were
      found in the control cytologic samples. The concentration of titanium was higher
      in the peri-implantitis group compared with the group without peri-implantitis;
      no traces of titanium were observed in controls. CONCLUSIONS: Regardless of an
      inflammatory response, ions/particles are released from the surface of the
      implant into the biologic milieu. Exfoliative cytology is a simple technique that
      may be used to detect metal particles in cells exfoliated from the peri-implant
      mucosa.

PMID- 22414262
TI  - Agreement between direct, oscillometric and Doppler ultrasound blood pressures
      using three different cuff positions in anesthetized dogs.
AB  - OBJECTIVE: To evaluate the agreement between invasive blood pressure (IBP) and
      Doppler ultrasound blood pressure (DUBP) using three cuff positions and
      oscillometric blood pressure (OBP) in anesthetized dogs. STUDY DESIGN:
      Prospective study. ANIMALS: Nine adult dogs weighing 14.5-29.5 kg. METHODS: The
      cuff was placed above and below the tarsus, and above the carpus with the DUBP
      and above the carpus with the OBP monitor. Based on IBP recorded via a dorsal
      pedal artery catheter, conditions of low, normal, and high systolic arterial
      pressures [SAP (mmHg) <90, between 90 and 140, and >140, respectively] were
      induced by changes in isoflurane concentrations and/or dopamine administration.
      Mean biases +/- 2 SD (limits of agreement) were determined. RESULTS: At high
      blood pressures, regardless of cuff position, SAP determinations with the DUBP
      underestimated invasive SAP values by more than 20 mmHg in most instances. With
      the DUBP, cuff placement above the tarsus yielded better agreement with invasive
      SAP during low blood pressures (0.2 +/- 16 mmHg). The OBP underestimated SAP
      during high blood pressures (-42 +/- 42 mmHg) and yielded better agreement with
      IBP for mean (MAP) and diastolic (DAP) arterial pressure measurements [overall
      bias: 2 +/- 15 mmHg (MAP) and 0.2 +/- 16 mmHg (DAP)]. CONCLUSIONS: Agreement of
      SAP determinations with the DUBP is poor at SAP > 140 mmHg, regardless of cuff
      placement. Measurement error of the DUBP with the cuff placed above the tarsus is
      clinically acceptable during low blood pressures. Agreement of MAP and DAP
      measurements with this OBP monitor compared with IBP was clinically acceptable
      over a wide pressure range. CLINICAL RELEVANCE: With the DUBP device, placing the
      cuff above the tarsus allows reasonable agreement with IBP obtained via dorsal
      pedal artery catheterization. Only MAP and DAP provide reasonable estimates of
      direct blood pressure with the OBP monitor evaluated.

PMID- 22414263
TI  - Impairments in daily functioning after heavy and extreme episodic drinking in
      university students.
AB  - INTRODUCTION AND AIM: Excessive consumption of alcohol is a major public health
      issue in university students. The dangers of heavy drinking are well known, with
      both acute and long-term consequences; however, there is limited information on
      patterns of extreme drinking (twice over the recommended threshold for low-risk
      drinking), and the differential effects of heavy versus extreme drinking on
      immediate consequent functioning in daily life. The current study investigated
      drinking patterns in a sample of university students and the association of
      different levels of alcohol consumption with self-reported physical, cognitive
      and emotional function the day after the drinking episode. DESIGN AND METHODS:
      Data for this study were collected from a sample of 281 University of Otago
      students using a 21 day Internet-based daily diary. Participants reported on
      their drinking the previous night and their physical, cognitive and emotional
      functioning on that day. RESULTS: Participants reported drinking on 26.8% days
      overall and consuming an average of 7.2 standard drinks per occasion. Only heavy
      drinking (7+standard drinks for men, 5+standard drinks for women) and
      particularly extreme drinking (14+for men, 10+for women) predicted significant
      decreases in physical and cognitive functioning the next day. However, low-risk
      drinking (<= 6 drinks for men,<= 4 for women) was not associated with next-day
      impairment. DISCUSSION AND CONCLUSIONS: Findings suggest that there are adverse,
      intermediate consequences of excessive drinking on dimensions relevant to
      students' lives. Drinking within low-risk guidelines is recommended.

PMID- 22414264
TI  - 3D Variation in delineation of head and neck organs at risk.
AB  - BACKGROUND: Consistent delineation of patient anatomy becomes increasingly
      important with the growing use of highly conformal and adaptive radiotherapy
      techniques. This study investigates the magnitude and 3D localization of
      interobserver variability of organs at risk (OARs) in the head and neck area with
      application of delineation guidelines, to establish measures to reduce current
      redundant variability in delineation practice. METHODS: Interobserver variability
      among five experienced radiation oncologists was studied in a set of 12 head and
      neck patient CT scans for the spinal cord, parotid and submandibular glands,
      thyroid cartilage, and glottic larynx. For all OARs, three endpoints were
      calculated: the Intraclass Correlation Coefficient (ICC), the Concordance Index
      (CI) and a 3D measure of variation (3D SD). RESULTS: All endpoints showed largest
      interobserver variability for the glottic larynx (ICC = 0.27, mean CI = 0.37 and
      3D SD = 3.9 mm). Better agreement in delineations was observed for the other OARs
      (range, ICC = 0.32-0.83, mean CI = 0.64-0.71 and 3D SD = 0.9-2.6 mm). Cranial,
      caudal, and medial regions of the OARs showed largest variations. All endpoints
      provided support for improvement of delineation practice. CONCLUSIONS: Variation
      in delineation is traced to several regional causes. Measures to reduce this
      variation can be: (1) guideline development, (2) joint delineation review
      sessions and (3) application of multimodality imaging. Improvement of delineation
      practice is needed to standardize patient treatments.

PMID- 22414265
TI  - Pediatric hydronephrotic segmental renal dysplasia with ipsilateral
      ureterovesical obstruction--rare coincidence or a consequence?
AB  - Obstruction in the developing urinary tract during embryonic life is one of the
      factors promoting disordered metanephric development in renal dysplasia.
      Dysplastic kidneys usually undergo involution during the first 5 years of life.
      Herein, we narrate a rare case of hydronephrotic segmental dysplasia co-existing
      with ipsilateral ureterovesical obstruction, in a 7-year-old male child,
      masquerading as hydronephrosis. Etiopathogenesis of segmental dysplasia
      presenting at this age is not clearly understood, and could be a consequence of
      intrauterine obstructive uropathy. Histologic evidence of dysplasia in a
      hydronephrotic kidney should warrant a close follow-up for pathologic changes in
      the contralateral kidney or urinary tract.

PMID- 22414266
TI  - Does neighborhood environment influence girls' pubertal onset? findings from a
      cohort study.
AB  - BACKGROUND: Pubertal onset occurs earlier than in the past among U.S. girls.
      Early onset is associated with numerous deleterious outcomes across the life
      course, including overweight, breast cancer and cardiovascular health. Increases
      in childhood overweight have been implicated as a key reason for this secular
      trend. Scarce research, however, has examined how neighborhood environment may
      influence overweight and, in turn, pubertal timing. The current study
      prospectively examined associations between neighborhood environment and timing
      of pubertal onset in a multi-ethnic cohort of girls. Body mass index (BMI) was
      examined as a mediator of these associations. METHODS: Participants were 213
      girls, 6-8 years old at baseline, in an on-going longitudinal study. The current
      report is based on 5 time points (baseline and 4 annual follow-up visits).
      Neighborhood environment, assessed at baseline, used direct observation. Tanner
      stage and anthropometry were assessed annually in clinic. Survival analysis was
      utilized to investigate the influence of neighborhood factors on breast and pubic
      hair onset, with BMI as a mediator. We also examined the modifying role of girls'
      ethnicity. RESULTS: When adjusting for income, one neighborhood factor
      (Recreation) predicted delayed onset of breast and pubic hair development, but
      only for African American girls. BMI did not mediate the association between
      Recreation and pubertal onset; however, these associations persisted when BMI was
      included in the models. CONCLUSIONS: For African American girls, but not girls
      from other ethnic groups, neighborhood availability of recreational outlets was
      associated with onset of breast and pubic hair. Given the documented risk for
      early puberty among African American girls, these findings have important
      potential implications for public health interventions related to timing of
      puberty and related health outcomes in adolescence and adulthood.

PMID- 22414267
TI  - Detecting aphid predation by earwigs in organic citrus orchards using molecular
      markers.
AB  - Aphids (Hemiptera: Aphidoidea) can damage citrus trees via direct damage to
      leaves and flowers or via the indirect transmission of viruses. Predators such as
      the European earwig, Forficula auricularia Linnaeus (Dermaptera: Forficulidae),
      may assist in keeping aphid populations under control in citrus orchards. Group
      specific primers were developed to detect aphid DNA in earwigs, in order to
      determine earwig predation rates in aphids in Mediterranean organic citrus trees.
      These primers were designed in accordance with the alignment of comparable
      sequences of aphids and earwigs, and they amplified a 224 bp fragment of the
      mitochondrial cytochrome c oxidase subunit I (COI) region. Following the
      consumption of three to five Aphis spiraecola Patch, aphid DNA was still
      detectable in 50% of earwigs one day after the ingestion. When predation was
      evaluated in the field, aphid DNA was detected in earwigs in May, June and July
      but not in April and August. The most interesting result is that of May, when
      aphid abundance was very low but 30% of the earwigs tested positive for aphid
      DNA. This finding suggests that earwigs are important aphid predators in citrus
      orchards, as they probably alter aphid dynamics as a result of early seasonal
      pressure on this pest. 

PMID- 22414268
TI  - Outcomes of herniotomy in premature infants: recent 10 year experience.
AB  - BACKGROUND: The timing of herniotomy in premature infants is controversial.
      METHODS: Outcomes of herniotomy in 47 premature infants admitted to the neonatal
      intensive care unit (NICU) were retrospectively reviewed for preoperative
      clinical features, respiratory interventions, and anesthetic and surgical
      complications. The data were compared with those of full-term infants (n = 52).
      Fourteen of the premature infants underwent herniotomy before NICU discharge and
      33 after discharge. The predictive factors for anesthetic and surgical
      complications were also investigated via multiple regression analysis. RESULTS:
      Mean post-conceptional age at surgery in premature infants and full-term infants
      was 47 weeks and 50 weeks, respectively. Mean bodyweight at surgery in those
      infants was 4087 g and 5454 g, respectively. The rate of incarcerated hernia and
      emergency surgery was lower in premature infants. Delayed extubation of the
      tracheal tube after surgery was noted in four premature infants, but not in full
      term infants. Two cases of cryptorchidism in premature infants and one recurrence
      in a full-term infant that required reoperation were noted. On multiple
      regression analysis no factor (including respiratory interventions) was found to
      be capable of predicting complications. CONCLUSION: Although no predictive factor
      for complications was identified, there were some anesthetic and surgical
      complications in premature infants. If there is no risk of incarceration,
      herniotomy in premature infants should be performed at a time when the risk of
      anesthetic complications is decreased. If there is a risk of incarcerated hernia,
      herniotomy should be performed carefully in order to avoid occurrence of
      anesthetic and surgical complications.

PMID- 22414269
TI  - Case of Mycobacterium haemophilum infection in a Japanese renal transplant
      patient and a review of Japanese cases.

PMID- 22414270
TI  - Resolving self-assembly of bile acids at the molecular length scale.
AB  - The self-assembly behavior of the naturally occurring steroidal bile compounds
      cholic, deoxycholic, ursodeoxycholic, and lithocholic acid was studied by
      combining atomic force microscopy (AFM), polarized optical microscopy (POM),
      Fourier-transform infrared spectroscopy (FTIR), absorption spectroscopy (UV-vis),
      circular dichroism (CD), and wide-angle X-ray scattering (WAXS). Molecular
      solutions of these mono-, di-, and trihydroxyl substituted bile acids
      spontaneously evolved into supramolecular aggregates upon the incremental
      addition of H(2)O as a poor solvent. Highly crystalline nanostructured
      multilayered assemblies were formed, which revealed a very rich polymorphism of
      micro- and macro-structures depending on the chemical structure of the bile acid
      and the properties of the cosolvent (EtOH or DMSO) used. In particular, AFM
      allowed resolving the crystalline structure to an unprecedented level. It was
      thus possible to establish that bile acids associate into H-bonded chiral dimer
      building blocks, which organize in 2D layers of nanostructured lamellar surface
      topologies with unique facial amphiphilicity. The detailed understanding of the
      hierarchical organization in bile acid assemblies may contribute to develop
      strategies to design bioinspired materials with tailor-made nanostructured
      surface topologies.

PMID- 22414271
TI  - Natural enamel caries in polarized light microscopy: differences in
      histopathological features derived from a qualitative versus a quantitative
      approach to interpret enamel birefringence.
AB  - Lesion area measurement of enamel caries using polarized light microscopy (PLM)
      is currently performed in a large number of studies, but measurements are based
      mainly on a mislead qualitative interpretation of enamel birefringence in a
      single immersion medium. Here, five natural enamel caries lesions are analysed by
      microradiography and in PLM, and the differences in their histopathological
      features derived from a qualitative versus a quantitative interpretation of
      enamel birefringence are described. Enamel birefringence in different immersion
      media (air, water and quinoline) is interpreted by both qualitative and
      quantitative approaches, the former leading to an underestimation of the depth of
      enamel caries mainly when the criterion of validating sound enamel as a
      negatively birefringent area in immersion in water is used (a current common
      practice in dental research). Procedures to avoid the shortcomings of a
      qualitative interpretation of enamel birefringence are presented and discussed.

PMID- 22414272
TI  - One-step homogeneous magnetic nanoparticle immunoassay for biomarker detection
      directly in blood plasma.
AB  - Assay technologies capable of detecting low biomarker concentrations in complex
      biological samples are fundamental for biological research and for applications
      in medical diagnostics. In this paper we address the challenge to perform protein
      biomarker detection homogeneously in one single step, applying a minute amount of
      reagent directly into whole human blood plasma, avoiding any sample dilution,
      separation, amplification, or fluid manipulation steps. We describe a one-step
      homogeneous assay technology based on antibody-coated magnetic nanoparticles that
      are spiked in very small amount directly into blood plasma. Pulsed magnetic
      fields and a double-linker molecular architecture are used to generate high
      biomarker-induced binding and low nonspecific binding between the nanoparticles.
      We demonstrate dose-response curves for prostate specific antigen (PSA) measured
      in undiluted human blood plasma with a detection limit of 400-500 femtomol/L, in
      a total assay time of 14 min and an optically probed volume of only 1 nL. We
      explain the dose-response curves with a model based on discrete binding of
      biomarker molecules onto the nanoparticles, which allows us to extract reaction
      parameters for the binding of biomarker molecules onto the nanoparticles and for
      the biomarker-induced binding between nanoparticles. The demonstrated analytical
      performance and understanding of the nanoparticle assay technology render it of
      interest for a wide range of applications in quantitative biology and medical
      diagnostics.

PMID- 22414273
TI  - Cholesteryl ester transfer protein gene polymorphisms increase the risk of fatty
      liver in females independent of adiposity.
AB  - BACKGROUND AND AIM: Environmental factors including excessive caloric intake lead
      to disordered lipid metabolism and fatty liver disease (FLD). However, FLD
      demonstrates heritability suggesting genetic factors are also important. We aimed
      to use a candidate gene approach to examine the association between FLD and
      single nucleotide polymorphisms (SNPs) in lipid metabolism genes in the
      adolescent population-based Western Australian Pregnancy (Raine) Cohort. METHODS:
      A total 951 seventeen year-olds underwent hepatic ultrasound, anthropometric and
      biochemical characterization, DNA extraction and genotyping for 57 SNPs in seven
      lipid metabolism genes (ApoB100, ATGL, ABHD5, MTTP, CETP, SREBP-1c, PPARalpha).
      Associations were adjusted for metabolic factors and Bonferroni corrected.
      RESULTS: The prevalence of FLD was 16.2% (11.4% male vs 21.2% female, P=0.001).
      Multivariate analysis of metabolic factors found suprailiac skinfold thickness
      (SST) to be the major predictor of FLD in females and males (odds ratio [OR]
      1.11, 95% confidence interval [CI] 1.08-1.15, P=1.7*10(-10) and OR 1.17, 95%CI
      1.13-1.22, P=2.4*10(-11) , respectively). In females, two SNPs in linkage
      disequilibrium from the CETP gene were associated with FLD: rs12447924 (OR 2.16,
      95%CI 1.42-3.32, P=0.0003) and rs12597002 (OR=2.22, 95%CI 1.46-3.41 P=0.0002). In
      lean homozygotes, the probability of FLD was over 30%, compared with 10-15% in
      lean heterozygotes and 3-5% in lean wild-types. However, these associations were
      modified by SST, such that for obese individuals, the probability of FLD was over
      30% in all genotype groups. CONCLUSIONS: Cholesteryl ester transfer protein gene
      polymorphisms are associated with an increased risk of FLD in adolescent females.
      The effect is independent of adiposity in homozygotes, thereby placing lean
      individuals at a significant risk of FLD.

PMID- 22414274
TI  - Low glycaemic variability in subjects with Type 2 diabetes following pre-Ramadan
      assessment and adjustments for fasting.

PMID- 22414275
TI  - Ribavirin restores ESR1 gene expression and tamoxifen sensitivity in ESR1
      negative breast cancer cell lines.
AB  - Tumor growth is estrogen independent in approximately one-third of all breast
      cancers, which makes these patients unresponsive to hormonal treatment. This
      unresponsiveness to hormonal treatment may be explained through the absence of
      the estrogen receptor alpha (ESR1). The ESR1 gene re-expression through
      epigenetic modulators such as DNA methyltransferase inhibitors and/or histone
      deacetylase inhibitors restores tamoxifen sensitivity in ESR1 negative breast
      cancer cell lines and opens new treatment horizons in patients who were
      previously associated with a poor prognosis.In the study presented herein, we
      tested the ability of ribavirin, which shares some structural similarities with
      the DNA-methyltransferase inhibitor 5-azacytidine and which is widely known as an
      anti-viral agent in the treatment of hepatitis C, to restore ESR1 gene re
      expression in ESR1 negative breast cancer cell lines.In our study we identified
      ribavirin to restore ESR1 gene re-expression alone and even more in combination
      with suberoylanilide hydroxamic acid (SAHA - up to 276 fold induction).Ribavirin
      and analogs could pave the way to novel translational research projects that aim
      to restore ESR1 gene re-expression and thus the susceptibility to tamoxifen-based
      endocrine treatment strategies.

PMID- 22414276
TI  - Interenzyme substrate diffusion for an enzyme cascade organized on spatially
      addressable DNA nanostructures.
AB  - Spatially addressable DNA nanostructures facilitate the self-assembly of
      heterogeneous elements with precisely controlled patterns. Here we organized
      discrete glucose oxidase (GOx)/horseradish peroxidase (HRP) enzyme pairs on
      specific DNA origami tiles with controlled interenzyme spacing and position. The
      distance between enzymes was systematically varied from 10 to 65 nm, and the
      corresponding activities were evaluated. The study revealed two different
      distance-dependent kinetic processes associated with the assembled enzyme pairs.
      Strongly enhanced activity was observed for those assemblies in which the enzymes
      were closely spaced, while the activity dropped dramatically for enzymes as
      little as 20 nm apart. Increasing the spacing further resulted in a much weaker
      distance dependence. Combined with diffusion modeling, the results suggest that
      Brownian diffusion of intermediates in solution governed the variations in
      activity for more distant enzyme pairs, while dimensionally limited diffusion of
      intermediates across connected protein surfaces contributed to the enhancement in
      activity for closely spaced GOx/HRP assemblies. To further test the role of
      limited dimensional diffusion along protein surfaces, a noncatalytic protein
      bridge was inserted between GOx and HRP to connect their hydration shells. This
      resulted in substantially enhanced activity of the enzyme pair.

PMID- 22414277
TI  - Catechol-O-methyltranferase gene expression is associated with response to
      citalopram in obsessive-compulsive disorder.
AB  - OBJECTIVE: To determine whether polymorphisms of the dopamine D(2) receptor
      (DRD2) and catechol-O-methyl-transferase (COMT) receptor genes affect the
      efficacy of quetiapine addition to citalopram in patients with OCD. METHODS:
      Sixty-four drug-free or drug-naive patients meeting DSM-IV criteria for OCD were
      randomized to 10 weeks double-blind treatment with citalopram (60 mg/day) with
      quetiapine (300 -450 mg/day) or with placebo. The change from baseline to
      endpoint on the total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the
      response to treatment were the primary outcome measures. Response was defined as
      a 25% decrease in Y-BOCS score. Responders and nonresponders were stratified
      according to DRD2 TaqI A and COMT Val(158)Met genotypes. RESULTS: No significant
      differences in genotype distribution or allele frequencies of the COMT or DRD2
      receptor were found between responders and nonresponders to citalopram with
      quetiapine. However, nearly half of responders to citalopram with placebo carried
      the Met/Met (48%) genotype of the COMT polymorphism compared to none of the
      nonresponders (chi(2) = 10.06, df = 2, P = 0.007). CONCLUSIONS: The Met allele
      load of the COMT receptor gene was associated with response to 10 weeks of
      treatment with citalopram in drug-free or drug-naive OCD patients.

PMID- 22414278
TI  - Bioconjugated and cross-linked bionanostructures for bifunctional
      immunohistochemical labeling.
AB  - The present study describes the development and use of a new bioconjugate
      combining targeted quantum dot labeling with an immunoperoxidase method and
      explores whether these bioconjugates could specifically and effectively label
      Cu/Zn superoxide dismutase (SOD1). The new bioconjugate is designed for the
      examination of samples both under fluorescent and bright-field microscopy at the
      same time. For this purpose chlorobis(2-2'-bipyridyl) methacryloyl tyrosine
      ruthenium(II) and bis (2-2'-bipyridyl) methacryloyltyrosine
      methacryloyltryptophan-ruthenium (II) photosensitive monomers and photosensitive
      poly(Bis (2-2'-bipyridyl)) methacryloyltyrosine-methacryloyltryptophan
      ruthenium(II) were synthesized and characterized. The anti-SOD1 antibody and
      horseradish peroxidase (HRD) conjugated quantum dots were prepared by using this
      polymer. The anti-SOD1 antibody and HRD conjugated quantum dots were used in
      labeling and imaging of SOD1 in rat liver sections. Quantum dot particles were
      observed as a bright fluorescence in their specific binding locations inside the
      hepatocytes. The HRD-diaminobenzidine reaction product was observed as brown
      colored particles at the same locations under bright-field microscopy. Structural
      details of the tissue sections could be examined at the same time. The
      conjugation protocol is simple; the bioconjugate is applicable for efficient cell
      labeling and can be adapted for imaging of other targets in different tissues.
      Also, the prepared nanobioconjugates have mechanic stability and can be used for
      a long period.

PMID- 22414279
TI  - Normal tissue complication probability modeling of acute hematologic toxicity in
      patients treated with intensity-modulated radiation therapy for squamous cell
      carcinoma of the anal canal.
AB  - PURPOSE: To identify dosimetric parameters that correlate with acute hematologic
      toxicity (HT) in patients with squamous cell carcinoma of the anal canal treated
      with definitive chemoradiotherapy (CRT). METHODS AND MATERIALS: We analyzed 33
      patients receiving CRT. Pelvic bone (PBM) was contoured for each patient and
      divided into subsites: ilium, lower pelvis (LP), and lumbosacral spine (LSS). The
      volume of each region receiving at least 5, 10, 15, 20, 30, and 40 Gy was
      calculated. Endpoints included grade >=3 HT (HT3+) and hematologic event (HE),
      defined as any grade >=2 HT with a modification in chemotherapy dose. Normal
      tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher
      Burman (LKB) model. Logistic regression was used to test associations between HT
      and dosimetric/clinical parameters. RESULTS: Nine patients experienced HT3+ and
      15 patients experienced HE. Constrained optimization of the LKB model for HT3+
      yielded the parameters m = 0.175, n = 1, and TD(50) = 32 Gy. With this model,
      mean PBM doses of 25 Gy, 27.5 Gy, and 31 Gy result in a 10%, 20%, and 40% risk of
      HT3+, respectively. Compared with patients with mean PBM dose of <30 Gy, patients
      with mean PBM dose >=30 Gy had a 14-fold increase in the odds of developing HT3+
      (p = 0.005). Several low-dose radiation parameters (i.e., PBM-V10) were
      associated with the development of HT3+ and HE. No association was found with the
      ilium, LP, or clinical factors. CONCLUSIONS: LKB modeling confirms the
      expectation that PBM acts like a parallel organ, implying that the mean dose to
      the organ is a useful predictor for toxicity. Low-dose radiation to the PBM was
      also associated with clinically significant HT. Keeping the mean PBM dose <22.5
      Gy and <25 Gy is associated with a 5% and 10% risk of HT, respectively.

PMID- 22414280
TI  - MGMT gene promoter methylation as a potent prognostic factor in glioblastoma
      treated with temozolomide-based chemoradiotherapy: a single-institution study.
AB  - PURPOSE: Recently, cells deficient in O(6)-methylguanine-DNA methyltransferase
      (MGMT) were found to show increased sensitivity to temozolomide (TMZ). We
      evaluated whether hypermethylation of MGMT was associated with survival in
      patients with glioblastoma multiforme (GBM). METHODS AND MATERIALS: We
      retrospectively analyzed 93 patients with histologically confirmed GBM who
      received involved-field radiotherapy with TMZ from 2001 to 2008. The median age
      was 58 years (range, 24-78 years). Surgical resection was total in 39 patients
      (42%), subtotal in 30 patients (32%), and partial in 17 patients (18%); only a
      biopsy was performed in 7 patients (8%). Postoperative radiotherapy began within
      3 weeks of surgery in 87% of the patients. Radiotherapy doses ranged from 50 to
      74 Gy (median, 70 Gy). MGMT gene methylation was determined in 78 patients; MGMT
      was unmethylated in 43 patients (55%) and methylated in 35 patients (45%). The
      median follow-up period was 22 months (range, 3-88 months) for all patients.
      RESULTS: The median overall survival (OS) was 22 months, and progression-free
      survival (PFS) was 11 months. MGMT gene methylation was an independently
      significant prognostic factor for both OS (p = 0.002) and PFS (p = 0.008) in
      multivariate analysis. The median OS was 29 months for the methylated group and
      20 months for the unmethylated group. In 35 patients with methylated MGMT genes,
      the 2-year and 5-year OS rates were 54% and 31%, respectively. Six patients with
      combined prognostic factors of methylated MGMT genes, age <=50 years, and
      total/subtotal resections are all alive 38 to 77 months after operation, whereas
      the median OS in 8 patients with unmethylated MGMT genes, age >50 years, and less
      than subtotal resection was 13.2 months. CONCLUSION: We confirmed that MGMT gene
      methylation is a potent prognostic factor in patients with GBM. Our results
      suggest that early postoperative radiotherapy and a high total/subtotal resection
      rate might further improve the outcome.

PMID- 22414281
TI  - Role of diffusion-weighted magnetic resonance imaging in predicting sensitivity
      to chemoradiotherapy in muscle-invasive bladder cancer.
AB  - PURPOSE: In chemoradiation (CRT)-based bladder-sparing approaches for muscle
      invasive bladder cancer (MIBC), patients who respond favorably to induction CRT
      enjoy the benefits of bladder preservation, whereas nonresponders do not. Thus,
      accurate prediction of CRT sensitivity would optimize patient selection for
      bladder-sparing protocols. Diffusion-weighted MRI (DW-MRI) is a functional
      imaging technique that quantifies the diffusion of water molecules in a
      noninvasive manner. We investigated whether DW-MRI predicts CRT sensitivity of
      MIBC. METHODS AND MATERIALS: The study cohort consisted of 23 MIBC patients
      (cT2/T3 = 7/16) who underwent induction CRT consisting of radiotherapy to the
      small pelvis (40 Gy) with two cycles of cisplatin (20 mg/day for 5 days),
      followed by partial or radical cystectomy. All patients underwent DW-MRI before
      the initiation of treatment. Associations of apparent diffusion coefficient (ADC)
      values with CRT sensitivity were analyzed. The proliferative potential of MIBC
      was also assessed by analyzing the Ki-67 labeling index (LI) in pretherapeutic
      biopsy specimens. RESULTS: Thirteen patients (57%) achieved pathologic complete
      response (pCR) to CRT. These CRT-sensitive MIBCs showed significantly lower ADC
      values (median, 0.63 * 10(-3) mm(2)/s; range, 0.43-0.77) than CRT-resistant (no
      pCR) MIBCs (median, 0.84 * 10(-3) mm(2)/s; range, 0.69-1.09; p = 0.0003).
      Multivariate analysis identified ADC value as the only significant and
      independent predictor of CRT sensitivity (p < 0.0001; odds ratio per 0.001 *10(
      3) mm(2)/s increase, 1.03; 95% confidence interval, 1.01-1.08). With a cutoff ADC
      value at 0.74 * 10(-3) mm(2)/s, sensitivity/specificity/accuracy in predicting
      CRT sensitivity was 92/90/91%. Ki-67 LI was significantly higher in CRT-sensitive
      MIBCs (p = 0.0005) and significantly and inversely correlated with ADC values
      (rho = -0.67, p = 0.0007). CONCLUSIONS: DW-MRI is a potential biomarker for
      predicting CRT sensitivity in MIBC. DW-MRI may be useful to optimize patient
      selection for CRT-based bladder-sparing approaches.

PMID- 22414282
TI  - Impact of different treatment approaches on pregnancy outcomes in 99 women
      treated for Hodgkin lymphoma.
AB  - PURPOSE: The aim of this study was to evaluate the pregnancy outcomes in women
      with Hodgkin lymphoma (HL) diagnosis, treated between 1972 and 1999 at Department
      of Radiotherapy and Hematology of University "Sapienza" of Roma. METHODS AND
      MATERIALS: We retrospectively studied 99 female patients that conceived after
      treatment for HL. Fifty-nine (59%) were treated with chemotherapy and
      radiotherapy, 32 (32%) with radiotherapy alone as supradiaphragmatic or as
      infradiaphragmatic and 8 (8%) patients with chemotherapy alone. RESULTS: Ninety
      nine patients reported 145 pregnancies. We observed 132 deliveries (2 of them
      twin births) after a median of 55 months (range, 14-278 months) from the end of
      therapy. Twelve women (12%) experienced 13 miscarriages after a median of 50
      months (range, 13-120) from the end of therapy. We recorded 9/132 (7%) premature
      births and 3/134 babies (2%) were underweight at the time of birth. We recorded 2
      cases of congenital malformations. No statistical differences were recorded when
      adverse pregnancy outcomes were analyzed with respect to chemotherapy alone,
      radiotherapy alone, or combined therapy. CONCLUSIONS: No significant associations
      between pregnancy outcomes and therapeutic approaches were found. In particular,
      the infradiaphragmatic radiotherapy showed no statistical association with
      miscarriages, premature birth, and low birth weight at term when compared with
      other therapeutic approaches.

PMID- 22414283
TI  - Recursive partitioning analysis for new classification of patients with
      esophageal cancer treated by chemoradiotherapy.
AB  - BACKGROUND: The 7th edition of the American Joint Committee on Cancer staging
      system does not include lymph node size in the guidelines for staging patients
      with esophageal cancer. The objectives of this study were to determine the
      prognostic impact of the maximum metastatic lymph node diameter (ND) on survival
      and to develop and validate a new staging system for patients with esophageal
      squamous cell cancer who were treated with definitive chemoradiotherapy (CRT).
      METHODS: Information on 402 patients with esophageal cancer undergoing CRT at two
      institutions was reviewed. Univariate and multivariate analyses of data from one
      institution were used to assess the impact of clinical factors on survival, and
      recursive partitioning analysis was performed to develop the new staging
      classification. To assess its clinical utility, the new classification was
      validated using data from the second institution. RESULTS: By multivariate
      analysis, gender, T, N, and ND stages were independently and significantly
      associated with survival (p < 0.05). The resulting new staging classification was
      based on the T and ND. The four new stages led to good separation of survival
      curves in both the developmental and validation datasets (p < 0.05). CONCLUSIONS:
      Our results showed that lymph node size is a strong independent prognostic factor
      and that the new staging system, which incorporated lymph node size, provided
      good prognostic power, and discriminated effectively for patients with esophageal
      cancer undergoing CRT.

PMID- 22414284
TI  - Reirradiation with cetuximab in locoregional recurrent and inoperable squamous
      cell carcinoma of the head and neck: feasibility and first efficacy results.
AB  - PURPOSE: To report our experience with a prospective protocol of external beam
      reirradiation (Re-RT) combined with cetuximab for patients with inoperable,
      recurrent squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND
      METHODS: Between August 2008 and June 2010, 18 patients with inoperable
      recurrence of SCCHN after adjuvant or definitive radiotherapy (RT) and
      simultaneous or sequential cisplatin-based chemotherapy for primary SCCHN were
      enrolled. Acute and late toxicity from the experimental regimen were recorded
      every week during RT and every 3 months thereafter. Efficacy was assessed with
      repeated imaging using response evaluation criteria in solid tumors and clinical
      examinations 8-12 weeks after completion of the treatment and every 3 months
      thereafter. RESULTS: Median follow-up time for all patients was 9.4 (range: 3.85
      31.7) months and for patients alive 30.4 (range: 15.7-31.7) months. Acute
      toxicity was generally mild or moderate. Five patients developed a grade 3
      acneiform rash related to cetuximab. Late toxicity occurred as grade 3 trismus in
      five and as grade 3 abacterial salivary gland inflammation in one patient,
      respectively. Overall response rate was 47%. Median overall and progression-free
      survival for all patients was 8.38 months and 7.33 months, respectively. The
      overall survival rate was 44% at 1 year, with a 1 year local control rate of 33%.
      CONCLUSION: Notwithstanding the limitations of our preliminary data Re-RT
      combined with cetuximab for recurrent and inoperable SCCHN is feasible and the
      integration of newer targeted agents seems to be less toxic compared to
      conventional chemotherapy with encouraging response rates at least for a subset
      of patients.

PMID- 22414285
TI  - Is image registration of fluorodeoxyglucose-positron emission tomography/computed
      tomography for head-and-neck cancer treatment planning necessary?
AB  - PURPOSE: To evaluate dosimetry and patterns of failure related to
      fluorodeoxyglucose-positron emission tomography (FDG-PET)-defined biological
      tumor volumes (BTVs) for head-and-neck squamous cell carcinoma (HNSCC) treated
      with definitive radiotherapy (RT). METHODS AND MATERIALS: We conducted a
      retrospective study of 91 HNSCC patients who received pretreatment PET/CT scans
      that were not formally used for target delineation. The median follow-up was 34.5
      months. Image registration was performed for PET, planning CT, and post-RT
      failure CT scans. Previously defined primary (CT(PRIMARY)) and nodal (CT(NODE))
      gross tumor volumes (GTV) were used. The primary BTV (BTV(PRIMARY)) and nodal BTV
      (BTV(NODE)) were defined visually (PET(vis)). The BTV(PRIMARY) was also contoured
      using 40% and 50% peak PET activity (PET(40,) PET(50)). The recurrent GTVs were
      contoured on post-RT CT scans. Dosimetry was evaluated on the planning-CT and
      pretreatment PET scan. PET and CT dosimetric/volumetric data was compared for
      those with and without local-regional failure (LRF). RESULTS: In all, 29 of 91
      (32%) patients experienced LRF: 10 local alone, 7 regional alone, and 12 local
      and regional. BTVs and CT volumes had less than complete overlap. BTVs were
      smaller than CT-defined targets. Dosimetric coverage was similar between failed
      and controlled groups as well as between BTVs and CT-defined volumes.
      CONCLUSIONS: PET and CT-defined tumor volumes received similar RT doses despite
      having less than complete overlap and the inaccuracies of image registration. LRF
      correlated with both CT and PET-defined volumes. The dosimetry for PET- and/or CT
      based tumor volumes was not significantly inferior in patients with LRF. CT-based
      delineation alone may be sufficient for treatment planning in patients with
      HNSCC. Image registration of FDG-PET may not be necessary.

PMID- 22414286
TI  - Pancreatic neuroendocrine tumors with involved surgical margins: prognostic
      factors and the role of adjuvant radiotherapy.
AB  - PURPOSE: Pancreatic neuroendocrine tumors (pNET) are rare neoplasms associated
      with poor outcomes without resection, and involved surgical margins are
      associated with a worse prognosis. The role of adjuvant radiotherapy (RT) in
      these patients has not been characterized. METHODS AND MATERIALS: We
      retrospectively evaluated 46 consecutive patients with positive or close (<1 mm)
      margins after pNET resection, treated from 1983 to 2010, 16 of whom received
      adjuvant RT. Median RT dose was 50.4 Gy in 1.8-Gy fractions; half the patients
      received concurrent chemotherapy with 5-fluorouracil or capecitabine. No patients
      received adjuvant chemotherapy. Cox multivariate analysis (MVA) was used to
      analyze factors associated with overall survival (OS). RESULTS: Median age at
      diagnosis was 56 years, and 52% of patients were female. Median tumor size was 38
      mm, 57% of patients were node-positive, and 11% had a resected solitary liver
      metastasis. Patients who received RT were more likely to have larger tumors
      (median, 54 mm vs. 30 mm, respectively, p = 0.002) and node positivity (81% vs.
      33%, respectively, p = 0.002) than those not receiving RT. Median follow-up was
      39 months. Actuarial 5-year OS was 62% (95% confidence interval [CI], 41%-77%).
      In the group that did not receive RT, 3 patients (10%) experienced local
      recurrence (LR) and 5 patients (18%) developed new distant metastases, while in
      the RT group, 1 patient (6%) experienced LR and 5 patients (38%) developed
      distant metastases. Of all recurrences, 29% were LR. On MVA, male gender
      (adjusted hazard ratio [AHR] = 3.81; 95% CI, 1.21-11.92; p = 0.02) and increasing
      tumor size (AHR = 1.02; 95% CI, 1.01-1.04; p = 0.007) were associated with
      decreased OS. CONCLUSIONS: Long-term survival is common among patients with
      involved-margin pNET. Despite significantly worse pathologic features among
      patients receiving adjuvant RT, rates of LR between groups were similar,
      suggesting that RT might aid local control, and merits further evaluation.

PMID- 22414287
TI  - Surface dose investigation of the flattening filter-free photon beams.
AB  - PURPOSE: Flattening filter-free (FFF) x-rays can provide more efficient use of
      photons and a significant increase of dose rate compared with conventional
      flattened x-rays, features that are especially beneficial for stereotactic
      radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). The available data
      on the entrance doses of the FFF photon beams remain limited. The purpose of this
      study was to investigate the entrance dose of FFF photons in the buildup region
      and to compare it with that of conventional flattened photons. METHODS AND
      MATERIALS: A Varian TrueBeam linear accelerator has been in full clinical
      operation with 6-MV and 10-MV FFF and flattened x-ray photons. Entrance dose at
      the surface was measured using a parallel plate ionization chamber in a solid
      water phantom with buildup depth = 0~15 mm for 6X and 0~25 mm for 10X. Different
      field size (FS) patterns were created in the Eclipse Treatment Planning System by
      multileaf collimator (MLC) rather than jaws (FS = 2 * 2, 3 * 3, 4 * 4, 6 * 6, and
      10 * 10 cm(2) by MLC and jaw size = 2.2 * 2.2, 3.2 * 3.2, 4.2 * 4.2, 6 * 6, and
      10 * 10 cm(2)). The smallest FS was about four times larger than the ion chamber
      dimension. All buildup dose measurements were normalized to FS = 10 * 10 cm(2) at
      the depth of dose maximum (dmax). RESULTS: Good repeatability was demonstrated
      and surface dose increased linearly with FS for both flattened and FFF photons.
      The entrance dose of the FFF photons was modestly larger than that of the
      corresponding flattened photons for both 6X and 10X for different FS ranging from
      2 * 2 cm(2) to 10 * 10 cm(2). CONCLUSIONS: The FFF photons have a higher entrance
      dose than that of the corresponding flattened photons for FS smaller than 10 * 10
      cm(2). However, the difference is not substantial and may be clinically
      insignificant.

PMID- 22414288
TI  - Simultaneous inhibition of EGFR and PI3K enhances radiosensitivity in human
      breast cancer.
AB  - PURPOSE: Mutations in the epidermal growth factor receptor
      (EGFR)/phosphoinositide 3-kinase (PI3K)/Akt signaling transduction pathway are
      common in cancer. This pathway is imperative to the radiosensitivity of cancer
      cells. We aimed to investigate the radiosensitizing effects of the simultaneous
      inhibition of EGFR and PI3K in breast cancer cells. METHODS AND MATERIALS: MCF-7
      cell lines with low expression of EGFR and wild-type PTEN and MDA-MB-468 cell
      lines with high expression of EGFR and mutant PTEN were used. The
      radiosensitizing effects by the inhibition of EGFR with AG1478 and/or PI3K with
      Ly294002 were determined by colony formation assay, Western blot was used to
      investigate the effects on downstream signaling. Flow cytometry was used for
      apoptosis and cell cycle analysis. Mice-bearing xenografts of MDA-MB-468 breast
      cancer cells were also used to observe the radiosensitizing effect. RESULTS:
      Simultaneous inhibition of EGFR and PI3K greatly enhanced radiosensitizing effect
      in MDA-MB-468 in terms of apoptosis and mitotic death, either inhibition of EGFR
      or PI3K alone could enhance radiosensitivity with a dose-modifying factor
      (DMF(SF2)) of 1.311 and 1.437, radiosensitizing effect was further enhanced by
      simultaneous inhibition of EGFR and PI3K with a DMF(SF2) at 2.698. DNA flow
      cytometric analysis indicated that dual inhibition combined with irradiation
      significantly induced G0/G1 phase arrest in MDA-MB-468 cells. The expression of
      phosphor-Akt and phosphor-Erk1/2 (induced by irradiation and PI3K inhibitor) were
      fully attenuated by simultaneous treatment with both inhibitors in combination
      with irradiation. In addition, dual inhibition combined with irradiation induced
      dramatic tumor growth delay in MDA-MB-468 xenografts. CONCLUSIONS: Our study
      indicated that simultaneous inhibition of EGFR and PI3K could further sensitize
      the cancer cells to irradiation compared to the single inhibitor with irradiation
      in vitro and in vivo. The approach may have important therapeutic implication in
      the treatment of a subset of breast cancer patients with high expression of EGFR
      and deficient function of PTEN.

PMID- 22414289
TI  - Quality of life scores as prognostic factors of overall survival in advanced head
      and neck cancer: analysis of a phase III randomized trial of pemetrexed plus
      cisplatin versus cisplatin monotherapy.
AB  - OBJECTIVES: We examined the prognostic factors (clinical, demographic, and health
      related quality of life [HRQoL]) of overall survival (OS) and progression-free
      survival (PFS) in patients with recurrent/metastatic head and neck cancer (HNC)
      who were treated with pemetrexed plus cisplatin versus cisplatin in a phase III,
      multinational, randomized trial. MATERIALS AND METHODS: Five subscales of the
      Functional Assessment of Cancer Therapy-Head and Neck Cancer (FACT-H&N), modified
      to score from 0 to 100, measured HRQoL at baseline and during treatment.
      Univariate and multivariate Cox proportional hazards models were used on data
      pooled from both treatment arms to assess the effect of baseline prognostic
      factors on OS and PFS. RESULTS: Of 795 patients randomized, 704 completed a
      baseline FACT-H&N and were included in the analysis. Age (<65 versus ?65;
      HR=0.74, 95% CI: 0.61-0.90), race (Caucasian versus non-Caucasian; HR=0.83, 95%
      CI: 0.70-0.98 per table), Eastern Cooperative Oncology Group performance status
      (ECOG PS; 0/1 versus 2; HR=0.44, 95% CI: 0.35-0.56), prior surgery/radiotherapy
      in the last 6months (no versus yes; HR=0.74, 95% CI: 0.61-0.90), and primary site
      of disease (oral cavity versus other; HR=1.37, 95% CI: 1.15-1.63) were
      significantly prognostic of OS in univariate models, as were baseline scores on
      four FACT-H&N subscales (physical well-being, emotional well-being, functional
      well-being, additional concerns-H&N; HRs=0.82-0.94; all P?0.002). In multivariate
      models, significant prognostic factors were age (HR=0.78); race (HR=0.76 per
      table); ECOG PS (HR=0.56); prior surgery/radiotherapy (HR=0.76); and baseline
      scores of the FACT-H&N subscales of physical well-being, social/family well
      being, and additional concerns-H&N (HRs=0.89-0.94; all P?0.014 per table).
      CONCLUSIONS: The results suggest that baseline HRQoL scores are prognostic
      indicators of OS in recurrent/metastatic HNC in addition to other known clinical
      and demographic indicators. HRQoL might be considered as a stratification factor
      in randomized clinical trials of recurrent/metastatic HNC.

PMID- 22414291
TI  - Transforming growth factor-beta enhances invasion and metastasis in Ras
      transfected human malignant epidermal keratinocytes.
AB  - Transforming growth factor-beta (TGF-beta) is known to act as a tumour suppressor
      early in carcinogenesis, but then switches to a pro-metastatic factor in some
      late stage cancers. However, the actions of TGF-beta are context dependent, and
      it is currently unclear how TGF-beta influences the progression of human squamous
      cell carcinoma (SCC). This study examined the effect of overexpression of TGF
      beta1 or TGF-beta2 in Ras-transfected human malignant epidermal keratinocytes
      that represent the early stages of human SCC. In vitro, the proliferation of
      cells overexpressing TGF-beta1 or TGF-beta2 was inhibited by exogenous TGF-beta1;
      cells overexpressing TGF-beta1 also grew more slowly than controls, but the
      growth rate of TGF-beta2 overexpressing cells was unaltered. However, cells that
      overexpressed either TGF-beta1 or TGF-beta2 were markedly more invasive than
      controls in an organotypic model of SCC. The proliferation of the invading TGF
      beta1 overexpressing cells in the organotypic assays was higher than controls.
      Similarly, tumours formed by the TGF-beta1 overexpressing cells following
      transplantation to athymic mice were larger than tumours formed by control cells
      and proliferated at a higher rate. Our results demonstrate that elevated
      expression of either TGF-beta1 or TGF-beta2 in cells that represent the early
      stages in the development of human SCC results in a more aggressive phenotype.

PMID- 22414292
TI  - Drug delivery in the nasal cavity after functional endoscopic sinus surgery: a
      computational fluid dynamics study.
AB  - BACKGROUND: Intranasal medication is commonly used for nasal disease. However,
      there are no clear specifications for intranasal medication delivery after
      functional endoscopic sinus surgery. METHODS: A three-dimensional model of the
      nasal cavity was constructed from computed tomography scans of an adult Chinese
      male who had previously undergone functional endoscopic sinus surgery in the
      right nasal cavity. Computational fluid dynamic simulations modelled airflow and
      particle deposition, based on discrete phase models. RESULTS: In the right nasal
      cavity, more particles passed through the upper dorsal region, around the
      surgical area, and streamed into the right maxillary sinus region. In the left
      cavity, particles were distributed more regularly and uniformly in the ventral
      region around the inferior turbinate. A lower inspiratory airflow rate and
      smaller initial particle velocity assisted particle deposition within the right
      maxillary sinus cavity. In the right nasal cavity, the optimal particle diameter
      was approximately 10(-5) m for maxillary sinus cavity deposition and 3 * 10(-6) m
      for bottom region deposition. In the right nasal cavity, altered back head tilt
      angles enhanced particle deposition in the top region of the surgical area, and
      altered right side head tilt angles helped enhance maxillary sinus cavity
      deposition. CONCLUSION: This model indicates that a moderate inspiratory airflow
      rate and a particle diameter of approximately 10(-5) m should improve intranasal
      medication deposition into the maxillary sinus cavity following functional
      endoscopic sinus surgery.

PMID- 22414293
TI  - An exploratory cluster randomised trial of a university halls of residence based
      social norms intervention in Wales, UK.
AB  - BACKGROUND: Excessive alcohol consumption amongst university students has
      received increasing attention. A social norms approach to reducing drinking
      behaviours has met with some success in the USA. Such an approach is based on the
      assumption that student's perceptions of the norms of their peers are highly
      influential, but that these perceptions are often incorrect. Social norms
      interventions therefore aim to correct these inaccurate perceptions, and in turn,
      to change behaviours. However, UK studies are scarce and it is increasingly
      recognised that social norm interventions need to be supported by socio
      ecological approaches that address the wider determinants of behaviour.
      OBJECTIVES: To describe the research design for an exploratory trial examining
      the acceptability, hypothesised process of change and implementation of a social
      norm marketing campaign designed to correct misperceptions of normative alcohol
      use and reduce levels of misuse, implemented alongside a university wide alcohol
      harm reduction toolkit. It also assesses the feasibility of a potential large
      scale effectiveness trial by providing key trial design parameters including
      randomisation, recruitment and retention, contamination, data collection methods,
      outcome measures and intracluster correlations. METHODS/DESIGN: The study adopts
      an exploratory cluster randomised controlled trial design with halls of residence
      as the unit of allocation, and a nested mixed methods process evaluation. Four
      Welsh (UK) universities participated in the study, with residence hall managers
      consenting to implementation of the trial in 50 university owned campus based
      halls of residence. Consenting halls were randomised to either a phased multi
      channel social norm marketing campaign addressing normative discrepancies (n = 25
      intervention) or normal practice (n = 25 control). The primary outcome is alcohol
      consumption (units per week) measured using the Daily Drinking Questionnaire.
      Secondary outcomes assess frequency of alcohol consumption, higher risk drinking,
      alcohol related problems and change in perceptions of alcohol-related descriptive
      and injunctive norms. Data will be collected for all 50 halls at 4 months follow
      up through a cross-sectional on line and postal survey of approximately 4000
      first year students. The process evaluation will explore the acceptability and
      implementation of the social norms intervention and toolkit and hypothesised
      process of change including awareness, receptivity and normative changes.
      DISCUSSION: Exploratory trials such as this are essential to inform future
      definitive trials by providing crucial methodological parameters and guidance on
      designing and implementing optimum interventions. TRIAL REGISTRATION NUMBER:
      ISRCTN: ISRCTN48556384.

PMID- 22414295
TI  - Nickel carbide as a source of grain rotation in epitaxial graphene.
AB  - Graphene has a close lattice match to the Ni(111) surface, resulting in a
      preference for 1 * 1 configurations. We have investigated graphene grown by
      chemical vapor deposition (CVD) on the nickel carbide (Ni(2)C) reconstruction of
      Ni(111) with scanning tunneling microscopy (STM). The presence of excess carbon,
      in the form of Ni(2)C, prevents graphene from adopting the preferred 1 * 1
      configuration and leads to grain rotation. STM measurements show that residual
      Ni(2)C domains are present under rotated graphene. Nickel vacancy islands are
      observed at the periphery of rotated grains and indicate Ni(2)C dissolution after
      graphene growth. Density functional theory (DFT) calculations predict a very weak
      (van der Waals type) interaction of graphene with the underlying Ni(2)C, which
      should facilitate a phase separation of the carbide into metal-supported
      graphene. These results demonstrate that surface phases such as Ni(2)C can play a
      major role in the quality of epitaxial graphene.

PMID- 22414294
TI  - Toxic epidermal necrolysis in a 4-year-old boy successfully treated with plasma
      exchange in combination with methylprednisolone and i.v. immunoglobulin.

PMID- 22414296
TI  - Profile of the static permittivity tensor of water at interfaces: consequences
      for capacitance, hydration interaction and ion adsorption.
AB  - We derive the theoretical framework to calculate the dielectric response tensor
      and determine its components for water adjacent to hydrophilic and hydrophobic
      surfaces using molecular dynamics simulations. For the nonpolarizable water model
      used, linear response theory is found to be applicable up to an external
      perpendicular field strength of ~2 V/nm, which is well beyond the experimental
      dielectric breakdown threshold. The dipole contribution dominates the dielectric
      response parallel to the interface, whereas for the perpendicular component it is
      essential to keep the quadrupole and octupole terms. Including the space
      dependent dielectric function in a mean-field description of the ion distribution
      at a single charged interface, we reproduce experimental values of the
      interfacial capacitance. At the same time, the dielectric function decreases the
      electrostatic part of the disjoining pressure between two charged surfaces,
      unlike previously thought. The difference in interfacial polarizability between
      hydrophilic and hydrophobic surfaces can be quantized in terms of the dielectric
      dividing surface. Using the dielectric dividing surface and the Gibbs dividing
      surface positions to estimate the free energy of a single ion close to an
      interface, ion-specific adsorption effects are found to be more pronounced at
      hydrophobic surfaces than at hydrophilic surfaces, in agreement with experimental
      trends.

PMID- 22414290
TI  - Neuropilins: expression and roles in the epithelium.
AB  - Initially found expressed in neuronal and then later in endothelial cells, it is
      well established that the transmembrane glycoproteins neuropilin-1 (NRP1) and
      neuropilin-2 (NRP2) play essential roles in axonal growth and guidance and in
      physiological and pathological angiogenesis. Neuropilin expression and function
      in epithelial cells has received little attention when compared with neuronal and
      endothelial cells. Overexpression of NRPs is shown to enhance growth, correlate
      with invasion and is associated with poor prognosis in various tumour types,
      especially those of epithelial origin. The contribution of NRP and its ligands to
      tumour growth and metastasis has spurred a strong interest in NRPs as novel
      chemotherapy drug targets. Given NRP's role as a multifunctional co-receptor with
      an ability to bind with disparate ligand families, this has sparked new areas of
      research implicating NRPs in diverse biological functions. Here, we review the
      growing body of research demonstrating NRP expression and role in the normal and
      neoplastic epithelium.

PMID- 22414297
TI  - Arterial stiffness and endothelial dysfunction independently and synergistically
      predict cardiovascular and renal outcome in patients with type 1 diabetes.
AB  - AIMS: To evaluate whether pulse pressure alone or with placental growth factor as
      estimates of arterial stiffness and endothelial dysfunction, predicts mortality,
      cardiovascular disease and progression to end-stage renal disease in patients
      with Type 1 diabetes. METHODS: Prospective, observational study, median (range)
      follow-up 8 (0-13) years, 900 patients with Type 1 diabetes, 458 with diabetic
      nephropathy, mean +/- SD age 44 +/- 11 years. RESULTS: During follow-up, we
      recorded 178 (20%) all-cause deaths, 109 (12%) cardiovascular deaths, 213 (24%)
      cardiovascular events and 73 (16%) progressed to end-stage renal disease.
      Elevated pulse pressure predicted all-cause and cardiovascular mortality and
      cardiovascular events [Hazard Ratio (HR) (95% CI) per 10 mmHg increase]: HR 1.2
      (1.1-1.3), 1.3 (1.2-1.5) and 1.2 (1.1-1.3), P<0.001 (adjusted for sex, age,
      HbA(1c) , cholesterol, diastolic blood pressure, creatinine, smoking, previous
      cardiovascular disease and nephropathy status). Furthermore, pulse pressure
      predicted the development of end-stage renal disease in patients with diabetic
      nephropathy: HR 1.2 (1.1-1.4), P=0.011 (adjusted for sex, age, HbA(1c) ,
      cholesterol, diastolic blood pressure, previous cardiovascular disease and
      glomerular filtration rate). In a two-hit model, patients with pulse pressure and
      placental growth factor levels above the median vs. below the median had
      increased risk of all-cause and cardiovascular mortality, cardiovascular events
      and progression to end-stage renal disease: adjusted HRs 2.3 (1.2-4.2), 4.2 (1.6
      11.0), 2.3 (1.3-4.1) and 3.5 (1.0-11.8),P<0.05. CONCLUSIONS: Elevated pulse
      pressure independently predicts mortality, cardiovascular events and progression
      to end-stage renal disease in patients with Type 1 diabetes. Placental growth
      factor adds to the predictive value of pulse pressure on cardiovascular and renal
      outcome.

PMID- 22414298
TI  - Lack of an association between E-selectin gene polymorphisms and risk of Kawasaki
      disease.
AB  - BACKGROUND: Coronary artery lesions (CAL) are a serious complication of Kawasaki
      disease (KD). The increased serum E-selectin level during the acute phase of KD
      and the association of E-selectin gene (SELE) polymorphisms with the prevalence
      of coronary artery disease in adults suggest a possible association between SELE
      polymorphisms and the development of CAL in KD patients. METHODS: The subjects
      consisted of 177 KD patients, including 59 with and 118 without CAL, and 305
      healthy controls. Two single nucleotide polymorphisms (SNP) of SELE, 98G>T
      (rs1805193) and Ser128Arg (rs5361), were genotyped by direct sequencing and the
      high-resolution melting curve method, respectively. The allele distributions were
      assessed using the chi-squared test. RESULTS: There were no significant
      differences in the T allele frequency at 98G>T between KD patients and controls
      (1.4% vs 1.0%, P = 0.55) or between KD patients with and without CAL (1.7% vs
      1.3%, P = 0.77). Similarly, there were no differences in the distribution of the
      C allele (128Arg) at Ser128Arg between KD patients and controls (4.5% vs 3.4%, P
      = 0.40) or between KD patients with and without CAL (4.2% vs 4.7%, P = 0.86).
      CONCLUSION: Although no association was detected between these SELE polymorphisms
      and the prevalence of KD or the development of CAL, this may have been due to the
      study limitations, including a low frequency of the minor alleles and a small
      sample size. A larger-scale association study is needed in order for a definitive
      conclusion to be made as to whether these SNP are associated with susceptibility
      to KD or not.

PMID- 22414299
TI  - Human cytomegalovirus UL94 is a nucleocytoplasmic shuttling protein containing
      two NLSs and one NES.
AB  - The tegument protein UL94 is a human cytomegalovirus (HCMV) late protein and its
      function has yet to be determined. Using live cell fluorescence recovery after
      photobleaching (FRAP) and fluorescence loss in photobleaching (FLIP) imaging, we
      found that UL94 is able to shuttle between the nucleus and cytoplasm. Analysis of
      UL94 mutants fused to EGFP showed that two newly characterized nuclear
      localization sequences (NLSs) and amino acid 343 play key roles in UL94 nuclear
      localization. Mutation of these sequences can alter the intracellular
      distribution of UL94 and disrupt its nucleocytoplasmic shuttling. Amino acid 343
      of UL94 was also found to be crucial for its interaction with another HCMV
      tegument protein pp28. Furthermore, one nuclear export sequence (NES) was
      identified within UL94. Mutation of the key amino acids in the NES can also alter
      the intracellular distribution of UL94 and disrupt its shuttling function. Like
      other proteins containing a leucine-rich export signal, nuclear export of the
      UL94 was affected by leptomycin B, indicating that it is exported via the Crm1
      dependent pathway. Our data provide a basis for further understanding the
      character and function of HCMV UL94.

PMID- 22414300
TI  - Suffocating cancer: hypoxia-associated epimutations as targets for cancer
      therapy.
AB  - Lower than normal levels of oxygen (hypoxia) is a hallmark of all solid tumours
      rendering them frequently resistant to both radiotherapy and chemotherapy
      regimes. Furthermore, tumour hypoxia and activation of the hypoxia inducible
      factor (HIF) transcriptional pathway is associated with poorer prognosis. Driven
      by both genetic and epigenetic changes, cancer cells do not only survive but
      thrive in hypoxic conditions. Detailed knowledge of these changes and their
      functional consequences is of great clinical utility and is already helping to
      determine phenotypic plasticity, histological tumour grading and overall
      prognosis and survival stratification in several cancer types. As epigenetic
      changes - contrary to genetic changes - are potentially reversible, they may
      prove to be potent therapeutic targets to add to the cancer physicians'
      armorarium in the future.Here, we review the therapeutic potential of epigenetic
      modifications (including DNA methylation, histone modifications and miRNAs)
      occurring in hypoxia with particular reference to cancer and tumourigenesis.

PMID- 22414301
TI  - Chondrogenic differentiation of human subchondral progenitor cells is affected by
      synovial fluid from donors with osteoarthritis or rheumatoid arthritis.
AB  - BACKGROUND: Microfracture is a first-line treatment option for cartilage repair.
      In microfracture, subchondral mesenchymal cortico-spongious progenitor cells
      (CSP) enter the defect and form cartilage repair tissue. The aim of our study was
      to investigate the effects of joint disease conditions on the in vitro
      chondrogenesis of human CSP. METHODS: CSP were harvested from the subchondral
      bone marrow. CSP characterization was performed by analysis of cell surface
      antigen pattern and by assessing the chondrogenic, osteogenic and adipogenic
      differentiation potential, histologically. To assess the effect of synovial fluid
      (SF) on chondrogenesis of CSP, micro-masses were stimulated with SF from healthy
      (ND), osteoarthritis (OA) and rheumatoid arthritis donors (RA) without
      transforming growth factor beta 3. RESULTS: CSP showed the typical cell surface
      antigen pattern known from mesenchymal stem cells and were capable of osteogenic,
      adipogenic and chondrogenic differentiation. In micro-masses stimulated with SF,
      histological staining as well as gene expression analysis of typical chondrogenic
      marker genes showed that SF from ND and OA induced the chondrogenic marker genes
      aggrecan, types II and IX collagen, cartilage oligomeric matrix protein (COMP)
      and link protein, compared to controls not treated with SF. In contrast, the
      supplementation with SF from RA donors decreased the expression of aggrecan, type
      II collagen, COMP and link protein, compared to CSP treated with SF from ND or
      OA. CONCLUSION: These results suggest that in RA, SF may impair cartilage repair
      by subchondral mesenchymal progenitor cells in microfracture, while in OA, SF may
      has no negative, but a delaying effect on the cartilage matrix formation.

PMID- 22414302
TI  - Weight management experiences of overweight and obese Canadian adults: findings
      from a national survey.
AB  - INTRODUCTION: We know little about how the 2006 Canadian Clinical Practice
      Guidelines for the management and prevention of obesity relate to Canadians'
      weight management experiences or whether these experiences reflect the
      recommendations in the Guidelines. METHODS: We used data from a general
      population omnibus survey to understand these two issues, particularly in
      relation to chronic disease. The survey included 23 questions related to weight
      management practices as well as those related to demographic characteristics.
      RESULTS: Of 2004 respondents, 33% were classified as overweight and 20% as obese.
      In the 12 months before the survey, 48% of overweight and obese respondents
      reported asking their physician about weight loss, while 30% reported that their
      physician advised them to lose weight without them specifically asking. With
      regard to the recommendations within the Guidelines, 14% of overweight and 18% of
      obese respondents reported having their waist circumference measured, 82% of
      overweight and 87% of obese respondents reported having their blood pressure
      measured, and 36% of overweight and 50% of obese respondents reported having a
      test for diabetes. CONCLUSION: These findings have implications for chronic
      disease identification and management.

PMID- 22414303
TI  - The National Population Health Survey's assessment of depression risk factor
      associations: a simulation study assessing vulnerability to bias.
AB  - BACKGROUND: In Canada, the major source of longitudinal information on major
      depression epidemiology has been the National Population Health Survey (NPHS).
      However, the timing of NPHS interviews may raise concerns about the quality of
      its estimates. Specifically, the NPHS interview assesses major depressive
      episodes (MDE) in the year before an interview, whereas the interviews are
      conducted 2 years apart. The objective of this study was to determine whether
      this aspect of the NPHS can be expected to introduce bias into longitudinal
      estimates of risk factor associations. METHODS: A simulation model was used to
      represent the underlying epidemiology and the expected results of a study
      adopting the NPHS approach to assessment of MDE. The model was used to explore
      the extent of the resulting distortion of estimates across a range of underlying
      hazard ratios. RESULTS: The simulations indicated that the timing and coverage of
      depression interviews in the NPHS would not introduce substantial bias. The model
      suggested that incidence would be underestimated as a result of episodes being
      missed, but that this would not substantially distort estimates of association.
      CONCLUSION: The timing of interviews in the NPHS is not expected to cause biased
      relative risk estimates. NPHS estimates may, of course, be influenced by other
      sources of bias.

PMID- 22414304
TI  - Dietary supplement use and iron, zinc and folate intake in pregnant women in
      London, Ontario.
AB  - INTRODUCTION: We examined the dietary intake of iron, zinc and folate, estimated
      from both food and supplement sources, in 2019 pregnant women who participated in
      the Prenatal Health Project (PHP). The PHP recruited pregnant women from
      ultrasound clinics in London, Ontario, in the years 2002-2005. METHODS:
      Participants completed a telephone survey, which included a food frequency
      questionnaire and questions on dietary supplement use. Frequencies of use of
      dietary supplements were generated. Nutrient intake values were estimated from
      food and supplement sources, and summed to calculate total daily intake values.
      RESULTS: Most women took a multivitamin supplement, and many women took folic
      acid and iron supplements; however, one-fifth of the sample did not take any
      supplements providing any of the three micronutrients. Despite being of a higher
      socio-economic status overall, significant proportions of the cohort ranked below
      the recommended dietary allowance values for iron, zinc, and folate. This
      suggests there may be other barriers that impact dietary practices. CONCLUSIONS:
      Further research is required on how to better promote supplement use and a
      healthy diet during pregnancy.

PMID- 22414305
TI  - Status report - National Epidemiologic Database for the Study of Autism in Canada
      (NEDSAC).

PMID- 22414306
TI  - Correlates of age at diagnosis of autism spectrum disorders in six Canadian
      regions.
AB  - INTRODUCTION: Early identification of autism spectrum disorders (ASD) is
      important, since earlier exposure to behavioural intervention programs may result
      in better outcomes for the child. Moreover, it allows families timely access to
      other treatments and supports. METHODS: Using generalized linear modeling, we
      examined the association between child and family characteristics and the age at
      which 2180 children were diagnosed with ASD between 1997 and 2005 in six Canadian
      regions. RESULTS: A diagnosis of pervasive developmental disorder-not otherwise
      specified (PDD-NOS) or Asperger syndrome, rural residence, diagnosis in more
      recent years, and foreign birthplace were associated with a later age at
      diagnosis. Children who are visible minorities or who have siblings with ASD were
      more likely to be diagnosed earlier. Collectively, these factors explained little
      of the variation in age at diagnosis, however. CONCLUSION: While it is
      encouraging that ethnocultural identity, neighbourhood income, urban or rural
      residence, and sex of the child were not major contributors to disparities in the
      age when children were identified with ASD, more work is needed to determine what
      does account for the differences observed. Regional variations in the impact of
      several factors suggest that aggregating data may not be an optimal strategy if
      the findings are meant to inform policy and clinical practice at the local level.

PMID- 22414307
TI  - The development of national indicators for the surveillance of osteoporosis in
      Canada.
AB  - INTRODUCTION: The Public Health Agency of Canada, in collaboration with bone
      health and osteoporosis experts from across Canada (n = 12), selected a core set
      of indicators for the public health surveillance of osteoporosis using a formal
      consensus process. METHODS: A literature review identified candidate indicators
      that were subsequently categorized into an osteoporosis-specific indicator
      framework. A survey was then administered to obtain expert opinion on the
      indicators' public health importance. Indicators that scored less than 3 on a
      Likert scale of 1 (low) to 5 (high) were excluded from further consideration.
      Subsequently, a majority vote on the remaining indicators' level of public health
      importance was sought during a face-to-face meeting. RESULTS: The literature
      yielded 111 indicators, and 88 were selected for further consideration via the
      survey. At the face-to-face meeting, more than half the experts considered 39
      indicators to be important from the public health perspective. CONCLUSION: This
      core set of indicators will serve to inform the development of new data sources
      and the integration, analysis and interpretation of existing data into
      surveillance products for the purpose of public health action.

PMID- 22414308
TI  - A new knowledge synthesis method that is applicable to public policies.

PMID- 22414309
TI  - Salmon fibrin treatment of spinal cord injury promotes functional recovery and
      density of serotonergic innervation.
AB  - The neural degeneration caused by spinal cord injury leaves a cavity at the
      injury site that greatly inhibits repair. One approach to promoting repair is to
      fill the cavity with a scaffold to limit further damage and encourage regrowth.
      Injectable materials are advantageous scaffolds because they can be placed as a
      liquid in the lesion site then form a solid in vivo that precisely matches the
      contours of the lesion. Fibrin is one type of injectable scaffold, but risk of
      infection from blood borne pathogens has limited its use. We investigated the
      potential utility of salmon fibrin as an injectable scaffold to treat spinal cord
      injury since it lacks mammalian infectious agents and encourages greater neuronal
      extension in vitro than mammalian fibrin or Matrigel(r), another injectable
      material. Female rats received a T9 dorsal hemisection injury and were treated
      with either salmon or human fibrin at the time of injury while a third group
      served as untreated controls. Locomotor function was assessed using the BBB
      scale, bladder function was analyzed by measuring residual urine, and sensory
      responses were tested by mechanical stimulation (von Frey hairs). Histological
      analyses quantified the glial scar, lesion volume, and serotonergic fiber
      density. Rats that received salmon fibrin exhibited significantly improved
      recovery of both locomotor and bladder function and a greater density of
      serotonergic innervation caudal to the lesion site without exacerbation of pain.
      Rats treated with salmon fibrin also exhibited less autophagia than those treated
      with human fibrin, potentially pointing to amelioration of sensory dysfunction.
      Glial scar formation and lesion size did not differ significantly among groups.
      The pattern and timing of salmon fibrin's effects suggest that it acts on
      neuronal populations but not by stimulating long tract regeneration. Salmon
      fibrin clearly has properties distinct from those of mammalian fibrin and is a
      beneficial injectable scaffold for treatment of spinal cord injury.

PMID- 22414310
TI  - Impact of inhibition of erythropoietin treatment-mediated neurogenesis in the
      dentate gyrus of the hippocampus on restoration of spatial learning after
      traumatic brain injury.
AB  - Our previous study demonstrates that delayed (initiated 24h post injury)
      erythropoietin (EPO) therapy for traumatic brain injury (TBI) significantly
      improves spatial learning. In this study, we investigated the impact of
      inhibition of EPO treatment-mediated neurogenesis on spatial learning after
      experimental TBI. Young male Wistar rats (318+/-7 g) were subjected to unilateral
      controlled cortical impact injury. TBI rats received delayed EPO treatment (5000
      U/kg in saline) administered intraperitoneally once daily at 1, 2, and 3 days
      post injury and intracerebroventricular (icv) infusion of either a mitotic
      inhibitor cytosine-b-D-arabinofuranoside or vehicle (saline) for 14 days. Another
      2 groups of TBI rats were treated intraperitoneally with saline and infused icv
      with either a mitotic inhibitor Ara-C or saline for 14 days. Animals receiving
      sham operation were infused icv with either Ara-C infusion or saline.
      Bromodeoxyuridine (BrdU) was administered to label dividing cells. Spatial
      learning was assessed using a modified Morris water maze test. Animals were
      sacrificed at 35 days after injury and brain sections stained for
      immunohistochemical analyses. As compared to the saline treatment,
      immunohistochemical analysis revealed that delayed EPO treatment significantly
      increased the number of BrdU-positive cells and new neurons co-stained with BrdU
      and NeuN (mature neuron marker) in the dentate gyrus in TBI rats. EPO treatment
      improved spatial learning after TBI. Ara-C infusion significantly abolished
      neurogenesis and spatial learning recovery after TBI and EPO treatment. Both EPO
      and Ara-C reduced the number of astrocytes and microglia/macrophages in the
      dentate gyrus after TBI. Our findings are highly suggestive for an important role
      of EPO-amplified dentate gyrus neurogenesis as one of the mechanisms underlying
      EPO therapeutic treatments after TBI, strongly indicating that strategies
      promoting endogenous neurogenesis may hold an important therapeutic potential for
      treatment of TBI.

PMID- 22414311
TI  - Molecular interactions of the phytotoxins destruxin B and sirodesmin PL with
      crucifers and cereals: metabolism and elicitation of plant defenses.
AB  - Destruxin B and sirodesmin PL are phytotoxins produced by the phytopathogenic
      fungi Alternaria brassicae (Berk.) Sacc. and Leptosphaeria maculans (asexual
      stage Phoma lingam), respectively. The molecular interaction of destruxin B and
      sirodesmin PL with cruciferous and cereal species was investigated using HPLC-ESI
      MS(n). It was determined that crucifers transformed destruxin B to
      hydroxydestruxin B, but sirodesmin PL was not transformed. Overall, the results
      suggest that the five cruciferous species Arabidopsis thaliana, Thellungiella
      salsuginea, Erucastrum gallicum, Brassica rapa and Brassica napus are likely to
      produce a destruxin B detoxifying enzyme (destruxin B hydroxylase), similar to
      other cruciferous species reported previously. In addition, HPLC analyses and
      quantification of the phytoalexins elicited in each cruciferous species by these
      phytotoxins indicates that sirodesmin PL elicits a larger number of phytoalexins
      than destruxin B. Interestingly, transformation of destruxin B appears to occur
      also in the cereals Avena sativa and Triticum aestivum; however, the various
      destruxin metabolites detected in these cereals suggest that these reactions are
      non-specific enzymatic transformations, contrary to those observed in crucifers,
      where only a main transformation pathway is detectable. None of the toxins appear
      to elicit production of metabolites in either A. sativa or T. aestivum.

PMID- 22414312
TI  - Influence of repeated short-term nitrogen limitations on leaf phenolics
      metabolism in tomato.
AB  - High concentrations of phenolics have been shown to play a role in plant
      resistance to pathogens. One way to obtain increased phenolic concentrations in
      plant tissues is to limit mineral nitrogen (N) availability; however, over long
      periods, this treatment will have a negative effect on plant growth. The aim of
      our study was to determine the effect of repeated short-term N limitations on
      plant growth and phenolic metabolism in leaves. Tomato plants (Solanum
      lycopersicum, cv. Pixie) were subjected to two successive 10-day N-limitation
      periods (0.15 mM NO(3)(-), 0.01 mM NH(4)(+)), followed by periods of full
      nutrient supply (15 mM NO(3)(-), 1.2 mM NH(4)(+)). Additionally, other plants
      were subjected to either of these two limitation periods, and a set of control
      plants was given a full nutrient supply during the entire period. The phenolic
      metabolism was monitored by measuring the leaf concentrations of chlorogenic
      acid, three flavonol glycosides (quercetin and kaempferol derivatives) and two
      major anthocyanins, together with the expression of eight structural genes and
      three transcription factors of the phenylpropanoid pathway. The relative growth
      rate of the plants decreased during the N-limitation periods but was restored as
      soon as N was resupplied. Each N-limitation period resulted in an up-regulation
      of the phenolic biosynthetic pathway, as demonstrated by an increase in the leaf
      phenolic concentration and an up-regulation of the related genes. The genes in
      the phenolic pathway were down-regulated immediately when N was resupplied;
      however, the leaf concentrations of several phenolics, particularly flavonol
      glycosides, were maintained at significantly higher levels than in the control
      plants for up to 17 days after the end of the first limitation. The amplitude of
      the increase in leaf phenolic concentration did not depend on the number of N
      limitation periods to which the plant was subjected, which indicates that the
      plants did not acclimate to nitrogen limitation. Successive N-limitation periods
      resulted in additive increases in flavonol glycoside concentrations.

PMID- 22414313
TI  - Quasi-output-cost-ratio, perceived voice quality, and subjective evaluation in
      female kindergarten teachers.
AB  - This study estimated vocal economy and investigated its relation to perceived
      voice quality and self-reported symptoms of vocal fatigue in kindergarten
      teachers. Quasi-output-cost ratio (QOCR) was calculated for sustained vowel [a:]
      at habitual loudness and at sound pressure level (SPL) of 90 dB(6cm). QOCR was
      calculated as (SPL/CQ(EGG)) * T/T(0), where CQ(EGG) is the contact quotient
      measured from the electroglottogram, T is the period length, and T(0) is
      arbitrarily set mean period length (0.005 s in females). QOCR correlated
      negatively with perceived firmness at standard SPL and with the evaluation of too
      high pitch for the subject at both SPLs. QOCR did not predict self-reported vocal
      fatigue. Further studies with connected speech and objectively stated loading
      symptoms are warranted.

PMID- 22414314
TI  - Development and evaluation of a modified Frequency Scale for the Symptoms of
      Gastroesophageal Reflux Disease to distinguish functional dyspepsia from non
      erosive reflux disease.
AB  - BACKGROUND AND AIM: The Frequency Scale for the Symptoms of Gastroesophageal
      Reflux Disease (FSSG) is the standard questionnaire used in Japan for the
      diagnosis of gastroesophageal reflux disease (GERD) and assessment of the
      response to treatment. We modified the FSSG in order to assess dyspepsia
      symptoms, and evaluated the modified questionnaire. METHODS: We modified the FSSG
      by adding two questions on interdigestive and postprandial epigastric pain. We
      then assessed the modified FSSG with 100 new untreated symptomatic patients
      presenting to hospital and in 200 subjects undergoing health checks. Endoscopic
      assessment of the esophagogastric junction was performed according to the
      modified Los Angeles classification with addition of Grade N (normal appearance)
      and Grade M (minimal change). Endoscopic images were assessed by five experienced
      endoscopists blinded to the questionnaire results. RESULTS: The 100 new patients
      included 16 with erosive GERD (>Grade A), 12 with peptic ulcer, and two with
      gastric cancer. Among the 70 patients with no evidence of organic disease, the
      modified FSSG diagnosed functional dyspepsia (FD) in 41 and non-erosive gastric
      disease (NERD) in 29. A significant difference was seen in the dyspepsia score
      between patients with FD and NERD. Subjects with endoscopic GERD undergoing
      health checks had significantly higher scores for all symptoms, reflux symptoms,
      and dyspeptic symptoms on the modified FSSG. CONCLUSION: The modified FSSG can
      clearly distinguish FD from NERD, and is useful for the assessment of dyspeptic
      symptoms.

PMID- 22414316
TI  - Two new nortriterpenoid saponins from Salicornia bigelovii Torr. and their
      cytotoxic activity.
AB  - Investigation of characteristic constituents of Salicornia bigelovii Torr. led to
      isolation of two new 30-nortriterpenoid glycosides, Bigelovii A (1), Bigelovii B
      (2), together with two known 30-nortriterpenoid glycosides 3-4 and three known
      oleanane-type triterpenoid glycosides 5-7. The structures of new compounds were
      elucidated by extensive 1D and 2D NMR, and MS spectroscopic analysis, and
      chemical evidences. All compounds were isolated for the first time from
      Chenopodiaceae. Thus compounds 1-4 were evaluated for their cytotoxicity and
      compouds 1, 3 showed moderate activity against four cell lines, HL-60
      (promyelocytic leukemia), MCF-7 (breast carcinoma), HepG2 (liver carcinoma) and
      A549 (lung carcinoma), with IC(50) values of 6.18, 78.08, 13.64 and >100MUM for
      1; 31.87, >100, ~100, >100MUM for 3, respectively.

PMID- 22414317
TI  - Chemical constituents of the aerial part of Derris elliptica.
AB  - A new coumaronochromone, 6,4'-dihydroxy-7,5' -dimethoxy-coumaronochromone (1),
      together with eleven known flavonoids (2-12) were isolated from the ethanol
      extract of the aerial part of Derris elliptica. Their structures were elucidated
      on the basis of spectroscopic analysis. Compounds 2, 4, 7, 8 and 9 exhibited
      moderate insecticidal activities against larvae of Aedes albopictus. All
      compounds showed strong cytotoxic activities against Spodoptera litura (SL) and
      Trichoplusia ni BTI-Tn-5B1-4 (Hi-5) cells comparison to positive control of
      rotenone.

PMID- 22414318
TI  - Co-encapsulation and sustained-release of four components in ginkgo terpenes from
      injectable PELGE nanoparticles.
AB  - It is difficult to develop injectable sustained delivery systems for herbal
      medicines because of their composition complexity. Encapsulating various
      compounds with different physiochemical properties and achieving their
      synchronized and sustained release seem too hard to realize. In this paper, an
      injectable nanoparticulate system based on an mPEG-PLGA-mPEG (PELGE) platform was
      prepared for co-encapsulation and sustained release of four active components
      (ginkgolides A, B, C and bilobalide) in Ginkgo biloba extract. Different carriers
      were screened by macrophage uptake experiment for their ability to be long
      circulation. Drug loaded nanoparticles were prepared with 10% PEG(2000) modified
      PLGA by a co-precipitation method. The encapsulation efficiency of the total
      ginkgo terpenes (GT) in the optimal formulation was 78.84+/-2.06% with a loading
      dose of 11.90+/-0.31mg/150mg PELGE. The particles exhibited a spherical shape
      with a mean diameter of 123.3+/-44.0nm and zeta potential of -30.86+/-2.49mV.
      Sustained and synchronized release of the four components from PELGE
      nanoparticles was observed both in vitro and in vivo, which was mainly
      contributed to the long circulation of PEGylated nanoparticles and the slow
      degradation of PLGA. The half-life time of the four terpenoid compounds were also
      significantly improved by incorporation into PELGE nanoparticles. The results
      indicate that a PELGE nanoparticle is a promising carrier system for sustained
      and synchronized release of herbal medicines containing multiple components.

PMID- 22414319
TI  - The effectiveness of a preferred intensity exercise programme on the mental
      health outcomes of young people with depression: a sequential mixed methods
      evaluation.
AB  - BACKGROUND: People with mental illness are more likely to suffer physical health
      problems than comparable populations who do not have mental illness. There is
      evidence to suggest that exercise, as well has having obvious physical benefits,
      also has positive effects on mental health. There is a distinct paucity of
      research testing its effects on young people seeking help for mental health
      issues. Additionally, it is generally found that compliance with prescribed
      exercise programmes is low. As such, encouraging young people to exercise at
      levels recommended by national guidelines may be unrealistic considering their
      struggle with mental health difficulties. It is proposed that an exercise
      intervention tailored to young people's preferred intensity may improve mental
      health outcomes, overall quality of life, and reduce exercise attrition rates.
      METHODS/DESIGN: A sequential mixed methods design will be utilised to assess the
      effectiveness of an individually tailored exercise programme on the mental health
      outcomes of young people with depression. The mixed methods design incorporates a
      Randomised Controlled Trial (RCT), focus groups and interviews and an economic
      evaluation. PARTICIPANTS: 158 young people (14-17 years) recruited from primary
      care and voluntary services randomly allocated to either the intervention group
      or control group. Intervention group: PARTICIPANTS will undertake a 12 week
      exercise programme of 12 * 60 minutes of preferred intensity aerobic exercise
      receiving motivational coaching and support throughout. PARTICIPANTS will also be
      invited to attend focus groups and 1-1 interviews following completion of the
      exercise programme to illicit potential barriers facilitators to participation.
      CONTROL GROUP: PARTICIPANTS will receive treatment as usual. PRIMARY OUTCOME
      MEASURE: Depression using the Children's Depression Inventory 2 (CDI-2).
      SECONDARY OUTCOME MEASURES: Quality of Life (EQ-5D), physical fitness (Borg RPE
      scale, heart rate), incidents of self-harm, treatment received and compliance
      with treatment, and the cost effectiveness of the intervention. Outcome measures
      will be taken at baseline, post intervention and 6 month follow up. DISCUSSION:
      The results of this study will inform policy makers of the effectiveness of
      preferred intensity exercise on the mental health outcomes of young people with
      depression, the acceptability of such an intervention to this population and its
      cost effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01474837.

PMID- 22414320
TI  - Flavonoids as modulators of memory and learning: molecular interactions resulting
      in behavioural effects.
AB  - There is considerable interest in the potential of a group of dietary-derived
      phytochemicals known as flavonoids in modulating neuronal function and thereby
      influencing memory, learning and cognitive function. The present review begins by
      detailing the molecular events that underlie the acquisition and consolidation of
      new memories in the brain in order to provide a critical background to
      understanding the impact of flavonoid-rich diets or pure flavonoids on memory.
      Data suggests that despite limited brain bioavailability, dietary supplementation
      with flavonoid-rich foods, such as blueberry, green tea and Ginkgo biloba lead to
      significant reversals of age-related deficits on spatial memory and learning.
      Furthermore, animal and cellular studies suggest that the mechanisms underpinning
      their ability to induce improvements in memory are linked to the potential of
      absorbed flavonoids and their metabolites to interact with and modulate critical
      signalling pathways, transcription factors and gene and/or protein expression
      which control memory and learning processes in the hippocampus; the brain
      structure where spatial learning occurs. Overall, current evidence suggests that
      human translation of these animal investigations are warranted, as are further
      studies, to better understand the precise cause-and-effect relationship between
      flavonoid intake and cognitive outputs.

PMID- 22414321
TI  - Olmsted syndrome: a new case complicated with easily broken hair and treated with
      oral retinoid.

PMID- 22414322
TI  - Accuracy of glycated haemoglobin in screening for pre-diabetes in Asian Indians-
      a community survey: the Chandigarh Urban Diabetes Study (CUDS).
AB  - AIM: To compare American Diabetes Association and International Expert Committee
      recommended cut-off values of HbA(1c) for detecting the presence of pre-diabetes
      against plasma glucose values obtained from oral glucose tolerance tests in Asian
      Indians. METHODS: A cross-sectional randomly sampled population survey involving
      2368 adults, aged >= 20 years. HbA(1c) was measured on a Bio-Rad 10 system in
      1972 subjects. RESULTS: Of the 1972 subjects studied, 329 were detected to have
      pre-diabetes based on isolated impaired fasting glucose in 125 subjects (6.3%),
      isolated impaired glucose tolerance in 141 subjects (7.1%) and the presence of
      both in 63 subjects (3.2%). The HbA(1c) cut-off of 34 mmol/mol (5.7%), as
      recommended by the American Diabetes Association for detecting the presence of
      pre-diabetes, showed sensitivity of 62%, specificity 77%, with a positive
      predictive value of 34.7%, a negative predictive value of 89.5% and accuracy of
      67.8%; whereas the HbA(1c) cut-off recommended by the International Expert
      Committee of 42 mmol/mol (6%) had a sensitivity of 36%, specificity of 90%,
      positive predictive value of 42.7%, negative predictive of 85.4% and an accuracy
      of 77%. However, both these HbA(1c) cut-offs underdiagnosed the presence of pre
      diabetes in 38 and 64% of these subjects, respectively. CONCLUSIONS: The American
      Diabetes Association and the International Expert Committee recommended HbA(1c)
      cut-off values and oral glucose tolerance tests identify different pre-diabetes
      cohorts. Long-term prospective studies are required to define the usefulness of
      one over the other.

PMID- 22414324
TI  - Redox-gated potential micellar carriers based on electrostatic assembly of soft
      coordination suprapolymers.
AB  - We report in this paper the release and uptake of charged payloads in redox
      responsive electrostatic micellar systems composed of negatively charged soft
      iron coordination suprapolymers and positively charged block copolymers. This
      micellar system was reported in our previous work (Yan, Y.; Lan, Y. R.; de
      Keizer, A.; Drechsler, M.; Van As, H.; Stuart, M. A. C.; Besseling, N. A. M.
      Redox responsive molecular assemblies based on metallic coordination polymers.
      Soft Matter, 2010, 6, 3244-3248), where we proposed that the system can be used
      as a redox-triggered release and uptake system. In this paper, we successfully
      selected a negatively charged fluorescent dye, eosin B, as a model cargo to track
      the release and upload process. Upon being compacted in the mixed micelles of
      coordination polymers and diblock copolymers, the fluorescence of eosin B was
      effectively quenched. Once reduction was conducted, excess negative charges were
      introduced to the mixed micelles so that the negatively charged eosin B was
      expelled out which was accompanied by the recovery of the fluorescence. The free
      negatively charged eosin B was able to be taken up by the Fe(II) micelles again
      if oxidation of Fe(II) was carried out since excess positive charges were
      produced. Beside eosin B, other charged species, such as various charged
      macromolecules, were tested to be capable of uptake and release by this micellar
      system. We suppose this system can be potentially used as a redox-gated micellar
      carrier for uptake and release of charged cargos.

PMID- 22414323
TI  - Epigenetic understanding of gene-environment interactions in psychiatric
      disorders: a new concept of clinical genetics.
AB  - Epigenetics is a mechanism that regulates gene expression independently of the
      underlying DNA sequence, relying instead on the chemical modification of DNA and
      histone proteins. Although environmental and genetic factors were thought to be
      independently associated with disorders, several recent lines of evidence suggest
      that epigenetics bridges these two factors. Epigenetic gene regulation is
      essential for normal development, thus defects in epigenetics cause various rare
      congenital diseases. Because epigenetics is a reversible system that can be
      affected by various environmental factors, such as drugs, nutrition, and mental
      stress, the epigenetic disorders also include common diseases induced by
      environmental factors. In this review, we discuss the nature of epigenetic
      disorders, particularly psychiatric disorders, on the basis of recent findings:
      1) susceptibility of the conditions to environmental factors, 2) treatment by
      taking advantage of their reversible nature, and 3) transgenerational inheritance
      of epigenetic changes, that is, acquired adaptive epigenetic changes that are
      passed on to offspring. These recently discovered aspects of epigenetics provide
      a new concept of clinical genetics.

PMID- 22414325
TI  - Particles and powders: tools of innovation for non-invasive drug administration.
AB  - The paper briefly illustrates several approaches applied in delivering
      particulate drugs as powders. Microparticulate drug powders are difficult to
      manipulate with respect to dosage form preparation, particularly when they have
      very small size as this leads to poor flow and packing properties. When the
      dosage form performance resides in the presence of individual intact drug
      particles, the particle characteristics have to be retained in their original
      state, i.e., not altered during manufacturing and/or within the dosage form.
      There are several examples of dry powder dosage forms intended for different
      administration routes whose performance is strictly dependent on particle
      characteristics. In addition, the preparation of the finished dosage form is
      dependent on powder properties. The paper addresses dry powder formulations with
      special focus on oral powders mainly for elderly people or children, nasal
      powders and inhalation dry powders. These dosage forms are very attractive for
      both researchers and companies. Their formulation requires deep investigation,
      mainly in order to define particle structure and performance. Indeed, this makes
      for a new breakthrough in pharmaceutics and may lead to innovative products.

PMID- 22414326
TI  - Value of amino-terminal pro B-natriuretic peptide in diagnosing Kawasaki disease.
AB  - BACKGROUND: The aim of the present study was to investigate the diagnostic value
      of the N-terminal B-type natriuretic peptide (NT-proBNP) in acute Kawasaki
      disease (KD) given that the clinical criteria and the current basic laboratory
      tests lack the necessary specificity for accurate diagnosis. METHODS: Basic
      biological tests and serum NT-proBNP levels obtained from acute KD patients were
      compared to that of febrile controls. NT-proBNP was considered abnormal based on
      the following definitions: above a cut-off determined on receiver operator
      characteristic (ROC) analysis, above the upper limit for age, or above 2 SD
      calculated from healthy children. Analyses were also performed for KD cases with
      complete or incomplete criteria combined and separately. RESULTS: There were 81
      patients and 49 controls aged 3.60 +/- 2.77 versus 4.25 +/- 3.88 years (P= 0.69).
      ROC analysis yielded significant area under the curve for NT-proBNP. The
      sensitivity, specificity, positive and negative predictive values were 70.4
      88.9%, 69.4-91.8%, 82.8-93.4%, and 65.2-79.1%. The odds ratios based on NT-proBNP
      definitions varied between 18.13 (95% confidence interval [CI]: 7.21-45.57),
      20.82 (95%CI: 8.18-53.0), and 26.71 (95%CI: 8.64-82.57; P < 0.001). Results were
      reproducible for cases with complete or incomplete criteria separately.
      CONCLUSION: NT-proBNP is a reliable marker for the diagnosis of KD. Prospective
      clinical studies with emphasis on NT-proBNP in a diagnostic algorithm are needed.

PMID- 22414327
TI  - Ectopic pancreas tissue appearing in a mediastinal cyst.
AB  - Heterotopia of pancreatic tissue is a common developmental anomaly. Although
      ectopic pancreatic tissue is mostly found in the gastrointestinal tract,
      localization in the mediastinum is extremely rare. We report a 32-year-old male
      patient who had an urgent thoracotomy two years ago due to a thoracic surgery.
      During the thoracotomy fragments of a partly necrotic cystic mass in the right
      thorax were removed and decortication was performed. Two years later the patient
      was hospitalized again because of haemoptysis and atypical chest pain. A residual
      cystic mass was detected between the right hilum and the ascending aorta
      connecting to the pericardium, the superior vena cava and the aorta on the chest
      CT. After the operation a mediastinal cyst was diagnosed, with a pancreatic
      tissue by histology.

PMID- 22414328
TI  - Oesophagostomum dentatum and Oesophagostomum quadrispinulatum: characterization
      of the complete mitochondrial genome sequences of the two pig nodule worms.
AB  - In the present study, the complete mitochondrial DNA (mtDNA) sequences of the pig
      nodule worm Oesophagostomum quadrispinulatum were determined for the first time,
      and the mt genome of Oesophagostomum dentatum from China was also sequenced for
      comparative analysis of their gene contents and genome organizations. The mtDNA
      sequences of O. dentatum China isolate and O. quadrispinulatum were 13,752 and
      13,681 bp in size, respectively. Each of the two mt genomes comprises 36 genes,
      including 12 protein-coding genes, two ribosomal RNA and 22 transfer RNA genes,
      but lacks the ATP synthetase subunit 8 gene. All genes are transcribed in the
      same direction and have a nucleotide composition high in A and T. The contents of
      A+T are 75.79% and 77.52% for the mt genomes of O. dentatum and O.
      quadrispinulatum, respectively. Phylogenetic analyses using concatenated amino
      acid sequences of the 12 protein-coding genes, with three different computational
      algorithms (maximum likelihood, maximum parsimony and Bayesian inference), all
      revealed that O. dentatum and O. quadrispinulatum represent distinct but closely
      related species. These data provide novel and useful markers for studying the
      systematics, population genetics and molecular diagnosis of the two pig nodule
      worms.

PMID- 22414329
TI  - Complete sequence analysis of 18S rDNA based on genomic DNA extraction from
      individual Demodex mites (Acari: Demodicidae).
AB  - The study for the first time attempted to accomplish 18S ribosomal DNA (rDNA)
      complete sequence amplification and analysis for three Demodex species (Demodex
      folliculorum, Demodex brevis and Demodex canis) based on gDNA extraction from
      individual mites. The mites were treated by DNA Release Additive and Hot Start II
      DNA Polymerase so as to promote mite disruption and increase PCR specificity.
      Determination of D. folliculorum gDNA showed that the gDNA yield reached the
      highest at 1 mite, tending to descend with the increase of mite number. The
      individual mite gDNA was successfully used for 18S rDNA fragment (about 900 bp)
      amplification examination. The alignments of 18S rDNA complete sequences of
      individual mite samples and those of pooled mite samples ( >= 1000mites/sample)
      showed over 97% identities for each species, indicating that the gDNA extracted
      from a single individual mite was as satisfactory as that from pooled mites for
      PCR amplification. Further pairwise sequence analyses showed that average
      divergence, genetic distance, transition/transversion or phylogenetic tree could
      not effectively identify the three Demodex species, largely due to the
      differentiation in the D. canis isolates. It can be concluded that the individual
      Demodex mite gDNA can satisfy the molecular study of Demodex. 18S rDNA complete
      sequence is suitable for interfamily identification in Cheyletoidea, but whether
      it is suitable for intrafamily identification cannot be confirmed until the
      ascertainment of the types of Demodex mites parasitizing in dogs.

PMID- 22414330
TI  - Larger biopsies evaluation of transient elastography for detecting advanced
      fibrosis in patients with compensated chronic hepatitis B.
AB  - BACKGROUND AND AIM: Although larger biopsies sample had been recommended for the
      study of non-invasive liver fibrosis assessment, few studies with larger biopsies
      for transient elastography (TE) detecting liver fibrosis had been reported. The
      present study tries to re-evaluate the performance of TE for detecting advanced
      fibrosis (>=F3) with larger biopsies in patients with compensated chronic
      hepatitis B. METHODS: A total of 375 compensated patients were analyzed, who had
      undergone liver biopsy, reliable TE and routine blood tests. RESULTS: The area
      under the receiver operating characteristic curve (AUC) was influenced by liver
      biopsy sample: 0.873 (95% confidence interval 0.838-0.909) in total patients,
      0.880 (0.844-0.917) in length >= 15 mm, 0.897 (0.863-0.932) in length >= 20 mm
      and 0.911 (0.874-0.949) in length >= 25 mm. In patients with sample length >= 20
      mm, the cutoffs to exclude and confirm advanced fibrosis were 7.1 kPa and 12.7
      kPa, respectively. Stratified by alanine aminotransferase of two times the upper
      limit of normal (ALT 2 * ULN), transient elastography detecting advanced fibrosis
      with the most efficiency by 72.5% of patients obviated from liver biopsy. In
      patients with normal bilirubin and ALT < 2 * ULN, the area was 0.921 (0.860
      0.982), and cutoffs for excluding and confirming diagnosis were 7.4 kPa and 10.6
      kPa, respectively; 80% of patients could be classified with or without advanced
      fibrosis (AF). In patients with normal bilirubin and ALT >= 2 * ULN, the
      corresponding numbers were 0.885 (0.824-0.947), 7.5 kPa, 12.7 kPa and 79.2%,
      respectively. CONCLUSIONS: Inadequate sample study would underestimate the
      efficiency of TE on detecting advanced fibrosis. With ALT 2 * ULN stratified
      cutoffs, TE determined nearly 80% of patients with normal bilirubin as AF or non
      AF and obviated them from liver biopsies.

PMID- 22414331
TI  - Improving the diagnostic yield of EEG tests.

PMID- 22414332
TI  - Sentence repetition and digit span: potential markers of bilingual children with
      suspected SLI?
AB  - PURPOSE: Digit span and sentence repetition are identified as potential markers
      for specific language impairment (SLI). We investigated if language learning of
      bilingual children with suspected language impairment (biSLI) was also influenced
      and led by memory constraints. METHOD: In a retrospective study, 19 children with
      SLI and 25 controls (ages 4;9-5;9), as well as 15 biSLI children and 14 controls
      (ages 5;1-8;9) were compared with regard to their performance on a digit span and
      sentence repetition task. RESULTS: Both groups with language impairment
      (SLI/biSLI) showed reduced performance on both tasks. Sentence repetition
      predicted language comprehension, and the digit span task predicted grammar
      abilities of the SLI, biSLI, and their controls. CONCLUSION: Sentence repetition
      and short-term memory provide information on language comprehension and grammar
      abilities in language-impaired mono- and bilingual children and confirm their
      function as SLI markers.

PMID- 22414334
TI  - Follicle stimulating hormone receptor G-29A, 919A>G, 2039A>G polymorphism and the
      risk of male infertility: a meta-analysis.
AB  - Studies of the relationship between male infertility and polymorphisms in the
      regions of FSHR G-29A (rs1394205), 919A>G (Thr(307)Ala, rs6165) and 2039A>G
      (Asn(680)Ser, rs6166) have reported inconsistent results. To assess the
      association between them, a meta-analysis was conducted. PubMed and CBMdisc
      literature search were conducted to identify all eligible studies investigating
      such a relationship. The pooled ORs were performed for co-dominant model,
      dominant model and recessive model in FSHR G-29A, Thr(307)Ala and Asn(680)Ser
      respectively to assess the strength of association. A total of 1644 male
      infertility cases and 1748 controls were collected from seven case-control
      studies. In the overall analysis, no significant association between the three
      polymorphisms and risk of male infertility was observed. Stratified analysis
      showed that there were no significantly increased risks of azoospermia and
      oligoasthenoteratozoospermia (OAT) in any of the genetic models. This meta
      analysis supports that FSHR G-29A, Thr(307)Ala and Asn(680)Ser polymorphisms may
      not be capable of causing male infertility susceptibility.

PMID- 22414335
TI  - High GC content of simple sequence repeats in Herpes simplex virus type 1 genome.
AB  - The presence, locations and composition of simple sequence repeats (SSRs) in
      Herpes simplex virus type 1 (HSV-1) genome were extracted and analyzed by using
      the software Imperfect Microsatellite Extractor (IMEx). There were 663 mon-, 502
      di-, 184 tri-, 20 tetra-, 4 penta- and 4 hexanucleotide SSRs that were observed
      in different distribution between coding and noncoding regions in the HSV-1
      genome. G/C, GC/CG, and (GGC)(n) were predominant in mononucleotide, dinucletide,
      trinucleotide repeats respectively. Indeed, the results showed that GC content in
      simple sequence repeats was notably higher than that in entire HSV-1 genome. Our
      data might be helpful for studying the pathogenesis, genome structure and
      evolution of HSV-1.

PMID- 22414336
TI  - Preferences of people with diabetes for diabetic retinopathy screening: a
      discrete choice experiment.
AB  - AIMS: The ever-increasing prevalence of diabetes places pressure on the provision
      of diabetic retinopathy screening services. As the first study of its kind, we
      aimed to determine preferences for diabetic retinopathy screening in people with
      diabetes and to examine the trade-offs between frequency of screening and other
      service attributes. METHODS: A questionnaire including a discrete choice
      experiment was administered to people (n = 198) attending diabetic retinopathy
      screening at eight clinics across Wales, United Kingdom. The discrete choice
      experiment contained eight pairwise choices in which screening provision was
      described by five attributes: frequency of screening; travel time; results time;
      ability of screening to detect other changes; and explanation of results. Data
      were analysed using logistic regression techniques. RESULTS: We gained a response
      rate of 86.4% from the 198 questionnaires administered at clinics; 160 complete
      responses were analysed. Respondents valued four out of the five attributes
      [ability of screening to detect other changes (P = 0.000), explanation of results
      (P = 0.024), frequency of screening (P = 0.000) and travel time (P = 0.007)].
      Results time was insignificant (P = 0.122). Respondents were willing to wait an
      additional 12, 2 and 1 month between screening tests to have a test that was able
      to detect additional changes, to have their results explained in person rather
      than by letter and to have a 15-min reduction in travel time, respectively.
      CONCLUSIONS: Respondents were willing to accept a longer screening interval, as
      long as preferences for other attributes of service provision (ability of
      screening to detect other changes, explanation of results and travel time) were
      made available.

PMID- 22414337
TI  - Early post-operative thrombosis of the prosthetic mitral valve in patient with
      heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is one of the most common immune-mediated
      adverse drug reactions, with frequencies as high as 2-3% for certain groups of
      post-cardiac surgery patients. We report on an 50-year-old woman with early post
      operative thrombosis of the prosthetic mitral valve due to heparin-induced
      thrombocytopenia. Non-invasive imaging (two-dimensional transesophageal
      echocardiography; 2D-TEE) allowed the exact localisation of thrombotic masses and
      revealed the increase of the mean diastolic mitral gradient. The HIT diagnosis
      was proved by the clinical scoring system, and with the identification of heparin
      platelet factor 4-induced antibodies. After the withdrawal of LMWH therapy and
      the start of intravenous lepirudin treatment, the patient's medical condition
      improved continuously. Follow-up echocardiography showed a step-wise decrease in
      the severity of the mean diastolic mitral valve gradient and a complete
      resolution of thrombus formations. Perhaps we may remind ourselves that, whilst
      HIT is one of the most common immune-mediated adverse drug reactions for certain
      groups of post-cardiac surgery patients, it can be managed successfully. We would
      also stress the importance of serial 2D-TEE examinations in the early post
      operative period.

PMID- 22414339
TI  - Hyper-aging dynamics of nanoclay suspension.
AB  - Aqueous suspension of nanoclay Laponite undergoes structural evolution as a
      function of time, which enhances its elasticity and relaxation time. In this
      work, we employ an effective time approach to investigate long-term relaxation
      dynamics by carrying out creep experiments. Typically, we observe that the
      monotonic evolution of elastic modulus shifts to lower aging times, while maxima
      in viscous moduli get progressively broader for experiments carried out on a
      later date after preparation (idle time) of the nanoclay suspension. Application
      of effective time theory produces a superposition of all the creep curves
      irrespective of their initial state. The resulting dependence of the relaxation
      time on aging time shows very strong hyper-aging dynamics at short idle times,
      which progressively weakens to demonstrate a linear dependence in the limit of
      very long idle times. Remarkably, this behavior of nanoclay suspensions is akin
      to that observed for polymeric glasses. Consideration of aging as a first-order
      process suggests that continued hyper-aging dynamics causes cessation of aging.
      The dependence of relaxation time on aging time, therefore, must attenuate
      eventually producing linear or weaker dependence on time in order to approach a
      progressively low-energy state in the limit of very long times as observed
      experimentally. We also develop a simple scaling model based on a concept of
      aging of an energy well, which qualitatively captures various experimental
      observations very well, leading to profound insight into the hyper-aging dynamics
      of nanoclay suspensions.

PMID- 22414338
TI  - The impact of obesity on the immune response to infection.
AB  - There is strong evidence indicating that excess adiposity negatively impacts
      immune function and host defence in obese individuals. This is a review of
      research findings concerning the impact of obesity on the immune response to
      infection, including a discussion of possible mechanisms. Obesity is
      characterised by a state of low-grade, chronic inflammation in addition to
      disturbed levels of circulating nutrients and metabolic hormones. The impact of
      these metabolic abnormalities on obesity-related comorbidities has undergone
      intense scrutiny over the past decade. However, relatively little is known of how
      the immune system and host defence are influenced by the pro-inflammatory and
      excess energy milieu of the obese. Epidemiological data suggest obese human
      subjects are at greater risk for nosocomial infections, especially following
      surgery. Additionally, the significance of altered immunity in obese human
      subjects is emphasised by recent studies reporting obesity to be an independent
      risk factor for increased morbidity and mortality following infection with the
      2009 pandemic influenza A (H1N1) virus. Rodent models offer important insight
      into how metabolic abnormalities associated with excess body weight can impair
      immunity. However, more research is necessary to understand the specific aspects
      of immunity that are impaired and what factors are contributing to reduced
      immunocompetence in the obese. Additionally, special consideration of how
      infection in this at-risk population is managed is required, given that this
      population may not respond optimally to antimicrobial drugs and vaccination.
      Obesity impacts millions globally, and greater understanding of its associated
      physiological disturbances is a key public health concern.

PMID- 22414341
TI  - Unraveling the mysterious role of palladium in Feigl
      bis(dimethylglyoximate)nickel(II) spot tests by means of confocal Raman
      microscopy.
AB  - The acid protection effect promoted by traces of PdCl(2) in [Ni(dmgH)(2)] spot
      tests was elucidated from confocal Raman microscopy imaging, which revealed the
      formation of protecting layers of [Pd(dmgH)(2)] closing the extremities of the
      [Ni(dmgH)(2)] filaments.

PMID- 22414340
TI  - Is Friedreich ataxia an epigenetic disorder?
AB  - Friedreich ataxia (FRDA) is a debilitating and frequently fatal neurological
      disorder that is recessively inherited. It belongs to the group of genetic
      disorders known as the Repeat Expansion Diseases, in which pathology arises from
      the deleterious consequences of the inheritance of a tandem repeat array whose
      repeat number exceeds a critical threshold. In the case of FRDA, the repeat unit
      is the triplet GAA*TTC and the tandem array is located in the first intron of the
      frataxin (FXN) gene. Pathology arises because expanded alleles make lower than
      normal levels of mature FXN mRNA and thus reduced levels of frataxin, the FXN
      gene product. The repeats form a variety of unusual DNA structures that have the
      potential to affect gene expression in a number of ways. For example, triplex
      formation in vitro and in bacteria leads to the formation of persistent RNA:DNA
      hybrids that block transcription. In addition, these repeats have been shown to
      affect splicing in model systems. More recently, it has been shown that the
      region flanking the repeats in the FXN gene is enriched for epigenetic marks
      characteristic of transcriptionally repressed regions of the genome. However,
      exactly how repeats in an intron cause the FXN mRNA deficit in FRDA has been the
      subject of much debate. Identifying the mechanism or mechanisms responsible for
      the FXN mRNA deficit in FRDA is important for the development of treatments for
      this currently incurable disorder. This review discusses evidence for and against
      different models for the repeat-mediated mRNA deficit.

PMID- 22414344
TI  - Breaching the skin barrier--insights from molecular simulation of model
      membranes.
AB  - Breaching the skin's barrier function by design is an important strategy for
      delivering drugs and vaccines to the body. However, while there are many proposed
      approaches for reversibly breaching the skin barrier, our understanding of the
      molecular processes involved is still rudimentary. Molecular simulation offers an
      unprecedented molecular-level resolution with an ability to reproduce molecular
      and bulk level properties. We review the basis of the molecular simulation
      methodology and give applications of relevance to the skin lipid barrier,
      focusing on permeation of molecules and chemical approaches for breaching the
      lipid barrier by design. The bulk kinetic model based on Fick's Law describing
      absorption of a drug through skin has been reconciled with statistical mechanical
      quantities such as the local excess chemical potential and local diffusion
      coefficient within the membrane structure. Applications of molecular simulation
      reviewed include investigations of the structure and dynamics of simple models of
      skin lipids, calculation of the permeability of molecules in simple model
      membranes, and mechanisms of action of the penetration enhancers, DMSO, ethanol
      and oleic acid. The studies reviewed illustrate the power and potential of
      molecular simulation to yield important physical insights, inform and rationalize
      experimental studies, and to predict structural changes, and kinetic and
      thermodynamic quantities.

PMID- 22414342
TI  - A cross-sectional description of social capital in an international sample of
      persons living with HIV/AIDS (PLWH).
AB  - BACKGROUND: Social capital refers to the resources linked to having a strong
      social network. This concept plays into health outcomes among People Living with
      HIV/AIDS because, globally, this is a highly marginalized population. Case
      studies show that modifying social capital can lead to improvements in HIV
      transmission and management; however, there remains a lack of description or
      definition of social capital in international settings. The purpose of our paper
      was to describe the degree of social capital in an international sample of adults
      living with HIV/AIDS. METHODS: We recruited PLWH at 16 sites from five countries
      including Canada, China, Namibia, Thailand, and the United States. Participants
      (n = 1,963) completed a cross-sectional survey and data were collected between
      August, 2009 and December, 2010. Data analyses included descriptive statistics,
      factor analysis, and correlational analysis. RESULTS: Participant's mean age was
      45.2 years, most (69%) identified as male, African American/Black (39.9%), and
      unemployed (69.5%). Total mean social capital was 2.68 points, a higher than
      average total social capital score. Moderate correlations were observed between
      self-reported physical (r = 0.25) and psychological condition (r = 0.36), social
      support (r = 0.31), and total social capital. No relationships between mental
      health factors, including substance use, and social capital were detected.
      CONCLUSIONS: This is the first report to describe levels of total social capital
      in an international sample of PLWH and to describe its relationship to self
      reported health in this population.

PMID- 22414345
TI  - Tracheobronchial aspiration of foreign bodies and rigid bronchoscopy in children.
AB  - BACKGROUND: A significant proportion of cases of tracheobronchial foreign body
      aspiration due to life-threatening condition is observed during childhood. The
      aim of the present study was to describe our experience with the diagnosis and
      treatment of foreign body aspirations during childhood and review published
      literature. METHODS: One hundred and eighty-four patients under 16 years of age
      with a tentative diagnosis of foreign body aspiration were retrospectively
      evaluated according to age, sex, patient delay symptoms at presentation, foreign
      body type, localization and the diagnostic and therapeutic methods used. RESULTS:
      The most frequently aspirated objects were shelled nuts and seeds such as
      sunflower seeds, pistachio and hazelnuts. The chief symptom was cough. On
      physical examination, the most frequent findings were unilateral decrease of
      respiratory sound on the affected side with coarsening and bronchi. While 51% of
      cases presented a radiological finding, chest X-ray was normal in the other. All
      patients underwent rigid bronchoscopy under general anesthesia and a foreign body
      was identified in 137 (74.3%). The rigid bronchoscopy intervention was used in
      some cases, especially in the presence of tracheal foreign bodies of organic
      origin. CONCLUSIONS: Tracheobronchial foreign body aspiration is a significant
      cause of childhood morbidity and mortality. Early diagnosis and treatment is of
      utmost importance. Rigid bronchoscopy under general anesthesia should be
      performed in all patients suspected of foreign body aspiration, which could
      minimize mortality and morbidity if performed by experienced personnel with safe
      methods.

PMID- 22414343
TI  - Dynamics of molecular responses to coxsackievirus B4 infection differentiate
      between resolution and progression of acute pancreatitis.
AB  - A coxsackievirus B4 induces acute pancreatitis with different outcomes. The study
      utilized a systems biology approach to identify molecular immune responses that
      differentiate between disease resolution and disease progression. The data
      establish a temporal pattern of host responses that differentiate the resolution
      of acute pancreatitis from the progression to chronic pancreatitis. A group of
      twenty-five genes exhibited characteristic expression profiles that were observed
      during the development of chronic pancreatitis but not during the resolution of
      disease. We postulate that the temporal dynamics of the twenty-five genes
      influence the development of pathogenic immune responses associated with chronic
      pancreatitis. Furthermore, a subset of eleven genes exhibited increased
      expression as viral titers waned. Of the eleven gene products, five are secreted
      molecules, TNF-alpha, IFN-gamma, CXCL10, IL-10, and IL-22b, and represent novel
      potential therapeutic targets since they can be readily modulated with antibodies
      against the specific cytokine/chemokine or with antibodies against the
      corresponding receptors.

PMID- 22414346
TI  - Does paracetamol prevent apnoea in infants? The current dilemma of evaluation of
      therapies in the absence of randomized controlled trials.

PMID- 22414349
TI  - Care of the dying patient: a neglected issue in Pakistani context.

PMID- 22414348
TI  - Contingency discriminability and the generalized matching law describe choice on
      concurrent ratio schedules of wheel-running reinforcement.
AB  - Belke (2010) showed that on concurrent ratio schedules, the difference in ratio
      requirements required to produce near exclusive preference for the lower ratio
      alternative was substantively greater when the reinforcer was wheel running than
      when it was sucrose. The current study replicated this finding and showed that
      this choice behavior can be described by the matching law and the contingency
      discriminability model. Eight female Long Evans rats were exposed to concurrent
      VR schedules of wheel-running reinforcement (30s) and the schedule value of the
      initially preferred alternative was systematically increased. Two rats rapidly
      developed exclusive preference for the lower ratio alternative, but the majority
      did not - even when ratios differed by 20:1. Analysis showed that estimates of
      slopes from the matching law and the proportion of reinforcers misattributed from
      the contingency discriminability model were related to the ratios at which near
      exclusive preference developed. The fit of these models would be consistent with
      misattribution of reinforcers or poor discrimination between alternatives due to
      the long duration of wheel running.

PMID- 22414350
TI  - Human papilloma virus and oral lesions in gutka eating subjects in Karachi.
AB  - OBJECTIVE: To determine the frequency of HPV in eaters of Gutka (betel, areca,
      lime and tobacco concoction), presenting with oral lesions. STUDY DESIGN: A
      descriptive study. PLACE AND DURATION OF STUDY: Ziauddin University Research
      Laboratory, from February to July 2010. METHODOLOGY: Subjects munching Gutka
      fulfilled the inclusion criteria. Samples were collected in the form of 20 - 40
      ml oral rinse from 262 subjects who were habitual eaters of Gutka after an
      informed consent. Gentle brushings from the lesion were taken from subjects with
      the help of a brush at the other end of dental floss and the oral rinse was
      stored at 4 degrees C until DNA extraction. DNA was extracted and PCR was
      performed using HPV consensus primers Gp5+/Gp6+. Oral cavity was examined for the
      presence of ulcer, trismus, sub-mucosal fibrosis, leukoplakia and/or warts.
      RESULTS: Out of 262 subjects, 42 were females and 220 males with an average age
      of 27+/- 10 years. HPV was positive in 47 subjects (17.9%). HPV frequency was
      2.7% greater in chewers with more than 10 years of habit compared to less than 10
      years. Examination of oral cavity showed 78% presenting with more than one
      complaint including oral ulcers (25%), rough mucosa (62%), sub-mucosal fibrosis
      (24%), leukoplakia (20%) and erythroplakia (10.6%). Highest frequency of HPV was
      observed in erythroplakia (25%). Association between presence of symptoms and HPV
      shows an ODDS RATIO: ad/bc= 4982/430=11.6. CONCLUSION: Oral lesions caused by
      constant exposure to Gutka are associated with high frequency of HPV infection,
      which may be a risk factor for squamous cell carcinoma of the oral cavity. People
      should be educated about the consequences of Gutka abuse.

PMID- 22414351
TI  - Nutritional status in patients with hepatitis C.
AB  - OBJECTIVE: To assess the nutritional status via the SGA (subjective global
      assessment) screening tool of patients at all stages of hepatitis C virus (HCV)
      liver disease. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Out
      patient Clinics of the Aga Khan University Hospital, Karachi, conducted from
      October 2009 to January 2011. METHODOLOGY: Patients with hepatitis C virus
      infection and their HCV-negative attendants were enrolled from the outpatient
      clinics, and categorized into 4 groups of 100 patients each: healthy controls
      (HC), those with chronic hepatitis C infection (CHC), compensated cirrhotics (CC)
      and decompensated cirrhotics (DC). The validated subjective global assessment
      (SGA) tool was used to assess nutritional status. RESULTS: A total of 400
      patients were enrolled. Most of the patients in the HC group were class 'A' (best
      nutritional status). In contrast, the majority (64%) in the DC group were in the
      class 'C' (worst status). The compensated cirrhosis (CC) group showed that 90% of
      patients were malnourished, while 98% of all patients were malnourished in the DC
      group, predominantly class 'C'. Most importantly, 14% of patients with chronic
      hepatitis C (CHC) also scored a 'B' on the SGA; which when compared to HC was
      statistically significant (p=0.005). As the groups progressed in their disease
      from CHC to DC, the transition in nutritional status from 'A' to 'C' between
      groups was statistically significant. CONCLUSION: Malnutrition occurs early in
      the course of HCV, and progresses relentlessly throughout the spectrum of
      HCVdisease.

PMID- 22414352
TI  - Transpapillary versus palatal injection technique for maxillary tooth
      extractions.
AB  - OBJECTIVE: To compare the pain during injection administration and efficacy of
      transpapillary injection with palatal injection for simple maxillary tooth
      extractions. STUDY DESIGN: Randomized control trial. PLACE AND DURATION OF STUDY:
      The oral and maxillofacial surgery department of Armed Forces Institute of
      Dentistry, Rawalpindi, Pakistan, from July to December 2009. METHODOLOGY:
      Patients requiring simple extraction in maxilla were randomly divided into two
      groups each consisting of 100 patients. Group 1 was given conventional palatal
      injection and served as a control, whereas Group 2 received the transpapillary
      injection. Two percent Lignocaine with Adrenaline (1:100,000) was used for both
      groups. Pain during injection and then during the extraction were recorded for
      both groups using the Visual Analogue Scale and Faces Pain Score Scales on
      specially designed proformas. The data was analyzed using SPSS version 17.0 and
      independent t-test was applied to compare pain between both groups. P-value of
      less than 0.05 was considered to be statistically significant. RESULTS: Group 1
      consisted of 61 males and 39 females with an age ranging from 11-73 years (mean=
      39.92 + 14.85 years) while Group 2 consisted of 59 males and 41 females with an
      age ranging from 10-70 years (mean= 39.31 + 18.53 years). Results of FPS and VAS
      scores for injection and procedure were analyzed using independent t-test.
      Difference of scores for pain during injection were found to be significant (p <
      0.05) while the scores for the procedure were seen to be statistically
      insignificant (p > 0.05) showing that transpapillary injection is equally
      effective for maxillary extractions as palatal injection but with significantly
      decreased pain during injection. CONCLUSION: Transpapillary injection is an easy
      and effective way of eliminating the pain of palatal injection for maxillary
      extractions.

PMID- 22414353
TI  - Enteric fever in Karachi: current antibiotic susceptibility of Salmonellae
      isolates.
AB  - OBJECTIVE: To determine the current sensitivity and resistance profile of
      Salmonellae (S.) isolates in a laboratory setting. STUDY DESIGN: An observational
      study. PLACE AND DURATION OF STUDY: Dr. Essa's Laboratory and Diagnostic Centre,
      Karachi, Pakistan, from November 2008 - October 2010. METHODOLOGY: Isolates from
      blood culture specimens of 481 bacteraemic patients were identified using
      conventional biochemical tests. Salmonellae was confirmed with specific antisera
      and their antibiograms determined by Kirby-Bauer Disc Diffusion method using 12
      relevant antibiotics. Inclusions of the study were bacteraemia documented in all
      blood samples positive for S. typhi, S. paratyphi-A and B. Exclusions were all
      samples other than blood and blood samples negative for S. typhi and S. paratyphi
      A and B during the same period. Multidrug resistance (MDR) of isolates was
      defined as the isolates showing resistance to all conventional anti-typhoid
      medicines i.e., Chloramphenicol, Ampicillin and Co-trimoxazole. RESULTS:
      Specimens (n=217) yielded 131 Salmonellae typhi (60.36%), 71 S. paratyphi-A
      (32.71%), and 15 S. paratyphi-B (6.9%); these were sensitive to the Quinolones
      [Enoxacin: 94.96% (n=91), Ciprofloxacin, 96.47% (n=182), Ofloxacin: 95.74%
      (n=203)], and Cephalosporins [Cefixime: 96.62% (n=202), Cefotaxime: 99.17%
      (n=206), Ceftriaxone: 98.79% (n=208)]. Resistance to Amoxicillin was 96.48%
      (n=128) and 29.91% (n=78) to Co-trimoxazole. About 62.64% (n=136) of the isolates
      were MDR strains. CONCLUSION: Ciprofloxacin is currently a suitable empirical
      choice in presumed enteric fever cases, but culture and sensitivity analysis
      should be encouraged and results incorporated in prescription strategy.
      Increasing frequency of S. paratyphi-A isolates possibly suggests incomplete
      coverage employing monovalent vaccine.

PMID- 22414354
TI  - Non-viral microbial keratitis: etiology, clinical features and visual outcome.
AB  - OBJECTIVE: To determine the etiology, clinical features and visual outcome in non
      viral microbial keratitis. STUDY DESIGN: An observational study (case series).
      PLACE AND DURATION OF STUDY: Department of Ophthalmology, Khyber Teaching
      Hospital, Peshawar, Pakistan, from January 2007 to December 2009. METHODOLOGY:
      Charts of all patients with infective keratitis treated at the department were
      reviewed. The data collected and recorded on a standardized form included age,
      gender, predisposing factors, microbiology results of culture and sensitivity,
      clinical features, treatment given, complications and visual acuity at last
      follow-up (at least 2 months). RESULTS: Among a total of 228 cases, 148 were male
      (64.9%) and 80 were female (35.1%). Mean age of the patients was 42.8 +/- 21.9
      years. Trauma was the most common (31.5%) predisposing factor followed by
      previous ocular surgery (8.8%) and use of topical steroids (6.6%). The most
      common isolate among positive cultures was Staphylococcus aureus isolated in
      31.4% (11/35) eyes followed by fungal hyphae in 25.7% (9/35) and Gram negative
      bacilli in 17.1% (6/35) eyes. Visual outcome was good (> 6/18) in 19.6 %,
      moderate (< 6/18 to 3 6/60) in 22% and poor (< 6/60) in 58.4%. CONCLUSION: The
      main predisposing factors in the studied group of patients with non-viral
      keratitis were ocular trauma and injudicious use of topical steroids. The most
      common microorganism involved was Staphylococcus aureus. Visual outcome was
      moderate to poor even after successful treatment.

PMID- 22414355
TI  - Ventilator-associated pneumonia in children.
AB  - OBJECTIVE: To determine the frequency of Ventilator-Associated Pneumonia (VAP)
      and to identify the associated factors, causative organisms and outcome of VAP in
      children admitted to ICU. STUDY DESIGN: Cross-sectional, observational study.
      PLACE AND DURATION OF STUDY: Medical ICU (MICU) of the Children's Hospital and
      Institute of Child Health, Lahore, from August 2008 to March 2009. METHODOLOGY:
      All children admitted to MICU and requiring ventilation during the study period
      were included and monitored for any features suggestive of VAP. Partial septic
      screen was done in all suspected cases. VAP was labelled when any patient on the
      ventilator for more than 48 hours had at least 2 of the following features of
      nosocomial infection - fever > 101 degrees F, TLC < 4000 or > 15000 per mm3,
      neutrophils > 85%, CRP > 48 mg/L or new findings on chest examination suggestive
      of pneumonia; and radiological evidence of new or progressive and persistent
      infiltrates. Percentages were compared using chi-square test with the
      significance at p-value less than 0.05. RESULTS: Of the 93 children requiring
      mechanical ventilation during the study period, 16 developed VAP (17%). Almost
      half (46%) were younger than 1 year with male to female ratio of 1.2:1. Children
      developing VAP required ventilation for 13.5 (+ 10.1) days compared to 7.7 (+
      5.5) days in those who did not develop VAP. The common organisms isolated were
      Pseudomonas, Klebsiella and E. coli. Factors associated with increased frequency
      of VAP included age less than 1 year, unplanned emergency intubation and use of
      continuous intravenous sedation. Features that strongly suggested underlying VAP
      included purulent tracheal secretions compared to increased secretions alone, CRP
      > 48 mg/L, positive radiological findings and positive tracheal aspirate culture.
      Overall mortality was 23% among the ventilated cohort. Thirty two percent of them
      had VAP compared to only 13% among those who survived to discharge (p = 0.03).
      CONCLUSION: The frequency of VAP was 17% in this series. Factors significantly
      associated with VAP were age less than 1 year, unplanned intubation and
      continuous sedation. The important predictors of VAP included purulent tracheal
      secretions, high CRP and persistent new radiological findings.

PMID- 22414356
TI  - Seminal volume in the investigation of male infertility.
AB  - OBJECTIVE: To determine the seminal volume among infertile males and the
      frequency distribution of hypospermic and hyperspermic patients in infertile
      males. STUDY DESIGN: Cross-sectional observational study. PLACE AND DURATION OF
      STUDY: Department of Reproductive Physiology/Health, Public Health Laboratories
      Division, National Institute of Health, Islamabad, from 2002 to 2009.
      METHODOLOGY: Semen examinations of infertile male were carried out according to
      the standardized method of the World Health Organization. Seminal volume of 2-6
      ml were considered normal, while volumes less than 2 ml and higher than 6 ml were
      considered hypospermic and hyperspermic respectively. RESULTS: Out of 1521
      patients, 355 were hypospermic (23.34%), 1046 were normospermic (68.78%) while
      120 were hyperspermic (7.88%). In the hypospermic cases, 57 out of 355 (16.05%)
      had a volume of less than 1 ml. Of those 57 patients, 34 were found to be
      azoospermic, 12 were asthenozoospermic, one each were terato- and polyzoospermic,
      while 6 had normal counts. Among the hyperspermic patients (n=120), 3 were
      azoospermic, 24 were oligozoospermic and 19 cases (15.84%) had count within the
      normal range, while 1 patient was polyzoospermic. Significant differences (p <
      0.05) were observed among azoospermic, oligoasthenozoospermic and
      teratozoospermic groups when comparing hypo and hyperspermic patients.
      CONCLUSION: Seminal volume is an important parameter for assessment of
      infertility investigation and its abnormalities constitute a valuable index of
      problems with the male partner, even if the count and motility are well within
      the acceptable limits.

PMID- 22414357
TI  - Body mass index and dynamic lung volumes in office workers.
AB  - OBJECTIVE: To measure the association of body mass index (BMI) to lung volumes
      assessed by spirometer. STUDY DESIGN: Cross-sectional analytical study. PLACE AND
      DURATION OF STUDY: Department of Physiology and Cell Biology, University of
      Health Sciences, Lahore, from February to August 2009. METHODOLOGY: Two hundred
      and twenty-five apparently healthy adult office workers of either gender aged >
      20 years were recruited. Height and weight were measured and BMI was calculated
      as kg/m2. Subjects were categorized as normal (BMI=18.5 to 24.9 kg/m2);
      overweight (BMI=25 to 29.9 kg/m2); and obese Class 1 (BMI=30 to 34.9 kg/m2) on
      the basis of BMI. Lung volumes were measured by digital spirometer and were
      reported as percentage of predicted values for forced vital capacity (FVC%),
      forced expiratory volume in first second (FEV1%) and ratio of FEV1 to FVC
      (FEV1:FVC). Groups were compared using t-test and ANOVA, correlation was assessed
      by Pearson's 'r'. RESULTS: Significant differences in lung volumes were found in
      different BMI categories. Obese subjects had significantly lower FVC% (p <
      0.0001), as well as significantly lower FEV1% (p = 0.003) as compared to normal
      subjects. There were significant linear relationships between obesity and PFTs.
      BMI had significant negative linear association with FVC% in overweight (r = 
      0.197) and obese (r = - 0.488); and with FEV1% in obese subjects (r = -0.510).
      Gender and age had no significant effect on mean values of PFTs. CONCLUSION:
      Obese individuals in this sample had significant decline in lung volumes.

PMID- 22414358
TI  - Posterior reversible encephalopathy syndrome (PRES).
AB  - Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic
      entity. Neurotoxicity with characteristic watershed CT/MR imaging features
      characterize this  condition. This case report describes PRES syndrome in a 35
      year-old patient admitted with eclampsia. On the first postpartum day; she
      developed severe headache, generalized tonic-clonic seizures and visual symptoms
      including transient visual loss. MRI scan of the brain showed symmetric areas of
      hyperintense signal on T2-weighted images in the occipital lobes bilaterally.
      Patient improved symptomatically. Repeat MRI of the brain 4 months after initial
      admission showed resolution of the previous abnormalities.

PMID- 22414359
TI  - Abdominal cocoon (sclerosing encapsulating peritonitis): a rare cause of
      intestinal obstruction.
AB  - A 24 years old lady presented with classical history of acute intestinal
      obstruction. There was a background history of chronic abdomen for 9 years. There
      was asymmetrical abdominal distension. On laparotomy, the entire small intestine
      was cocooned and enclosed in a yellowish white thick fibrotic membrane resulting
      in obstruction of the small intestine. When the membrane was carefully peeled off
      the small intestine, the underlying small gut was found to be absolutely healthy.
      The histopathology report was consistent with non-specific dense fibrosis. Based
      on these findings, a diagnosis of abdominal cocoon or sclerosing encapsulating
      peritonitis was made which is an extremely rare cause of small bowel obstruction.

PMID- 22414360
TI  - Bouveret's syndrome: successful endoscopic treatment of gastric outlet
      obstruction caused by an impacted gallstone.
AB  - Bouveret's syndrome is defined as gastric outlet obstruction caused by duodenal
      impaction of a large gallstone which passes into the duodenal bulb through a
      cholecystogastric or cholecystoduodenal fistula. This is a report of a 62 years
      old female who presented with complaint of persistent vomiting and upper
      abdominal pain for the last 5 days. Ultrasound abdomen was suggestive of
      pneumobilia. CT scan of upper abdomen showed cholecystoduodenal fistula and
      complete obstruction of third part of duodenum by a large stone, which was
      reported as Bouveret's syndrome. She underwent  emergency gastroscopy. The stone
      was retrieved by Dormia basket, crushed with lithotripter and extracted
      endoscopically.Complete intestinal obstruction was relieved endoscopically.

PMID- 22414361
TI  - Bilateral brachial plexus injury.
AB  - Brachial plexus injuries can occur as a result of various mechanisms such as
      stretching, direct and indirect trauma or following childbirth. Bilateral
      brachial plexus injuries are uncommon and associated with a poor functional
      outcome. We report a case of bilateral brachial plexus injury resulting from
      prolonged immobilization of the arms in hyper-abducted position resulting in
      compression of the brachial plexus on both sides. The injuries were treated
      conservatively and following 4 months of active rehabilitation in our unit, the
      patient still had poor arm functions and required care and support in the
      community on discharge.

PMID- 22414362
TI  - Brown-McLean syndrome with keratoconus.
AB  - We report a case of unilateral Brown-McLean syndrome (peripheral corneal oedema)
      with bilateral keratoconus. A 30 years old lady presented with decreased vision
      in her right eye for the last 2 years. There was no history of surgery or trauma.
      Patient had no systemic illness. There was peripheral concentric corneal oedema
      extending 2.5-3.5 mm from the limbus involving right eye. On topography, we found
      bilateral keratoconus. To the best of our knowledge, this combination of Brown
      McLean syndrome and keratoconus has not been reported before.

PMID- 22414363
TI  - Patella dislocation association with drop foot.
AB  - All limb injuries should be examined with complete documentation of neurovascular
      assessment as they are often ignored in the busy emergency department setup. This
      may lead to delay in such diagnosis during the treatment of limb injuries at a
      follow-up in orthopaedic clinics. Early diagnosis can help orthopaedic team to
      investigate and start treatment which may help in the recovery of such
      neurovascular injuries. We report a case of missed neurovascular assessment in
      the emergency department on a patellar dislocation of a young person leading to
      foot drop and sensory numbness in the deep peroneal nerve distribution, which
      improved completely within three and a half months with conservative treatment.
      This is also the first reported case of foot drop in association with patellar
      dislocation.

PMID- 22414365
TI  - Rapidly progressive periodontal disease associated with human immunodeficiency
      virus.
AB  - Severe periodontal inflammation with generalized dental plaque accumulation,
      spontaneous and severe gingival bleeding, fungal infection, and interdental
      papillae necrosis are presented in a patient infected with human immunodeficiency
      virus (HIV). Bite-wing radiographs revealed a generalized horizontal alveolar
      bone loss of 7-8 millimetres in both arches. Erythematous patches were noted on
      the gingival mucosa in both jaws. DNA testing was performed to indentify the
      periodontopathogens. The patient had no signs or symptoms of acquired
      immunodeficiency syndrome. This case-report presents the massive periodontal
      destruction that occurred in a patient infected with HIV. Therefore, it is highly
      recommended that patients infected with HIV should be regularly monitored to aid
      in early detection and to provide proper management of periodontal inflammatory
      conditions to minimize its destruction.

PMID- 22414364
TI  - Malignant transformation of a potentially low risk lichenoid reaction.
AB  - Lichenoid reaction represents a family of oral lesions identical, both clinically
      and histologically to oral lichen planus. The triggering factor for this lesion
      varies from medicines to dental materials, usually demonstrating a cause-effect
      relationship unlike lichen planus. We present a typical case of lichenoid
      reaction on the buccal mucosa that appeared in response to betel quid which
      progressed to carcinoma during a follow-up period of 6 months. Lichenoid
      reactions occurring in response to known carcinogens and that occurring in risk
      group population has to be observed more cautiously.

PMID- 22414366
TI  - Pneumothorax in pregnancy secondary to ruptured pulmonary hydatid cyst.
AB  - Hydatid disease in pregnancy is a rare condition. Ruptured pulmonary hydatid cyst
      with pneumothorax during pregnancy is potentially serious for both the patient
      and the fetus. Diagnosis, treatment, and the mode of delivery of the infant all
      present complex problems related to this event. We describe here a case of
      pneumothorax occurring during pregnancy secondary to ruptured pulmonary hydatid
      cyst with a good outcome for both the mother and the fetus.

PMID- 22414367
TI  - Bleeding disorders in obstetrics and gynaecological practice.
AB  - The objective of the study was to determine the frequency, types, presenting
      symptoms and management options in patients with bleeding disorders in the local
      obstetric and gynaecological practice. This was a descriptive study of oneyear
      duration conducted at the Pakistan Atomic Energy Commission General Hospital,
      Islamabad. Types of bleeding disorders in decreasing order of frequency were
      HELLP syndrome in 27.7% (n=5), gestational thrombocytopenia in 22% (n=4), Von
      Willbrand disease in 16.66% (n=3), Glanzmann's thrombesthenia in 11.11% (n=2),
      autoimmune haemolytic anaemia in 11.11% (n=2), post-transfusion purpura in 6%
      (n=1) and factor V deficiency in 6% (n=1). HELLP syndrome and gestational
      thrombocytopenia were the commonest bleeding disorders in pregnant patients and
      Von Willebrand disease is the the commonest bleeding disorder in gynaecological
      patients with menorrhagia.

PMID- 22414368
TI  - Retention of knowledge of the Paediatric Life Support guidelines.
AB  - Paediatric Life Support (PLS) courses are thought to significantly increase
      knowledge of paediatric resuscitation for all professional groups. PLS and
      Newborn Life Support (NLS) guidelines were revised and updated in 2005. In a
      telephonic survey, the retention and awareness of the changes in PLS guidelines
      were evaluated among 100 junior paediatric doctors. Overall, second on-call
      doctors tended to score higher than the first on-call doctors (score 6.55 +/-
      2.25 vs. 5.89 +/- 2.17 respectively, p = 0.062). Doctors who attended PLS courses
      after 2005 tended to have higher scores. There is a need to streamline formalised
      regular updates (e.g. annual online written multiple choice questions) and in
      house rehearsals using mock emergency scenarios at local, regional and national
      level.

PMID- 22414369
TI  - Pott's puffy tumour.

PMID- 22414371
TI  - Taurine attenuates maternal and embryonic oxidative stress in a streptozotocin
      diabetic rat model.
AB  - Oxidative stress mechanisms have been implicated in congenital anomalies and
      morbidity/mortality of fetus/newborn in diabetic pregnancy. Numerous antioxidant
      treatments have shown varied beneficial effects in improving both maternal and
      fetal outcomes. The present study examined the propensity of taurine to attenuate
      the degree of embryopathy and oxidative stress among pregnant diabetic rats.
      Adult rats (CFT-Wistar) were rendered diabetic with an acute dose of
      streptozotocin (STZ; 45 mg/kg bodyweight) on gestation day (GD) 4. Both Diabetic
      and non-diabetic dams were given oral supplements of taurine (0.5 and 1g/kg
      bodyweight/day) from GD 5 to GD 12. Maternal diet intake, bodyweight gain and
      urine output were monitored and dams were killed on GD 13. Markers of oxidative
      stress were determined in embryos and maternal livers. STZ treatment induced
      marked embryopathy (32%) and taurine supplements markedly reduced the degree of
      embryopathy (54% protection). The STZ-induced higher oxidative stress was
      significantly attenuated in rats given taurine supplements (P<0.05) and a similar
      effect was seen in embryos (P<0.05). These data suggest that dietary taurine
      during pregnancy provides significant protection against diabetes-induced
      oxidative stress in both the mother and the embryos and thus may serve as a
      therapeutic supplement during diabetic pregnancy. Diabetes during pregnancy
      affects >5% of all pregnancies, causing reproductive abnormalities that enhance
      spontaneous abortion - congenital anomalies, morbidity and mortality of both
      mother and fetus/newborn. One of the major mechanisms is increased oxidative
      stress caused by hyperglycaemia and the most prominent anti-teratogenic effect
      was achieved using antioxidative agents. Management of oxidative stress is
      considered, along with tight glycaemic control, to be beneficial both before
      conception and during pregnancy. Taurine, a ubiquitous amino acid found in almost
      all mammalian tissues, constitutes more than 50% of free amino acids. The aim of
      the study was to determine whether oral taurine supplementation given to pregnant
      diabetic rats during the post-implantation period could reduce embryo lethality
      and protect the developing embryos against maternal hyperglycaemia-induced
      oxidative stress. Adult rats were rendered diabetic with an acute dose of
      streptozotocin on gestation day (GD) 4. Both diabetic and non-diabetic dams were
      administered oral taurine for a period of 8 days (GD 5-13). Maternal diet intake,
      bodyweight gain and urine output were monitored and dams were killed on GD 13.
      Markers of oxidative stress and antioxidant defences were studied in embryos and
      maternal livers. STZ induced marked embryopathy (32%) and taurine supplementation
      offered significant protection (54%). Taurine significantly offset diabetes
      associated oxidative stress in the embryos of diabetic rats. These data suggest
      that dietary taurine supplementation during pregnancy provides significant
      protection against diabetes-induced oxidative stress both in mother and embryos
      and thus may serve as a therapeutic supplement under diabetic pregnancy.

PMID- 22414372
TI  - Ovarian biopsy has no role as a routine diagnostic test of ovarian reserve: a
      systematic review.
AB  - Ovarian reserve describes a woman's reproductive potential and there are a
      variety of tests for this. This reflects the lack of a gold standard and the lack
      of a single test that provides sufficient accuracy. Ovarian biopsy has been
      proposed as a potential tool for assessing the ovarian reserve and therefore the
      ability or inability for a woman to bear a child with or without treatment. The
      literature assessing the diagnostic accuracy of ovarian biopsy as a test of
      ovarian reserve for predicting fertility outcomes (live birth rate, ongoing
      pregnancy, clinical pregnancy, biochemical pregnancy, embryos available, oocytes
      retrieved or cancelled cycles) was systematically reviewed. There were no studies
      identified that assessed the diagnostic accuracy of ovarian biopsy for predicting
      fertility outcomes but a number of studies provided evidence that ovarian
      follicles are distributed unevenly and randomly throughout the ovarian cortex.
      This leads to sampling error when ovarian biopsy is used to sample the ovarian
      reserve. It is concluded that ovarian biopsy should not be used as a test of
      ovarian reserve. Every woman is born with a limited number of eggs, and as women
      age, their ability to have children eventually decreases to zero due to the loss
      of these eggs. Ovarian reserve is a term that describes the remaining pool of
      eggs. Testing for ovarian reserve enables one to predict the ability or inability
      of a woman to have a child and how long a woman may be able to defer having a
      child. This is of importance as social trends in developed countries are leading
      to increasing numbers of women who have children at later stages of their lives.
      One test of ovarian reserve is an ovarian biopsy, where a woman undergoes an
      operation to have a small piece of her ovary removed. The number of eggs in this
      removed piece is counted, and from this, the number of eggs in the whole ovary
      can be estimated and calculated. We reviewed the literature for all studies that
      examined the accuracy of ovarian biopsy to predict fertility outcomes but found
      no studies that answered this question. A number of studies have found that eggs
      are distributed unevenly and randomly in an ovary. As such, the number of eggs in
      an ovarian biopsy sample does not represent the actual number of eggs remaining
      in the ovary. Because of this and the risks inherent in the operation to perform
      this test, we believe that ovarian biopsy should not be used as a test of ovarian
      reserve.

PMID- 22414373
TI  - Can oestradiol pretreatment be used to reliably avoid weekend oocyte retrievals?
AB  - Scheduling the initiation of ovarian stimulation in a gonadotrophin-releasing
      hormone (GnRH)-antagonist protocol by sex steroid pretreatment has been suggested
      as a means to reduce the incidence of oocyte retrievals during weekends. The
      rationale is that by manipulating the initiation of gonadotrophin stimulation,
      Thursday or Friday will be avoided as days on which triggering of final oocyte
      maturation will be performed and thus weekend oocyte retrievals will not occur.
      Apparently, the assumption behind such an approach is that duration of
      stimulation is homogenous enough to serve this purpose reliably. However,
      existing data suggest that large inter-individual variation exists in the
      duration of gonadotrophin stimulation required to reach predefined criteria for
      triggering final oocyte maturation, regardless of whether stimulation was
      initiated with spontaneous menstruation or after pretreatment with sex-steroids.
      Therefore, it is highly unlikely that any type of pretreatment aiming to allow
      initiation of stimulation on a certain day will result in avoidance of weekend
      oocyte retrievals, when predefined criteria for triggering final oocyte
      maturation are used.

PMID- 22414374
TI  - Survey of residual nitrite and nitrate in conventional and
      organic/natural/uncured/indirectly cured meats available at retail in the United
      States.
AB  - A survey of residual nitrite (NO(2)(-)) and nitrate (NO(3)(-)) in cured meats
      available at retail was conducted to verify concentrations in conventional (C)
      products and establish a baseline for organic/natural/uncured/indirectly cured
      (ONC) products. In this study, 470 cured meat products representing six major
      categories were taken from retail outlets in five major metropolitan cities
      across the United States. Random samples representing both C and ONC type
      products were analyzed for NO(2)(-) and NO(3)(-) content (ppm) using an ENO-20
      high-performance liquid chromatography system equipped with a reverse phase
      column. Generally, there were no differences in NO(2)(-) concentrations between C
      and ONC meat categories, but a few ONC products surveyed in certain cities were
      lower in NO(3)(-) content. Pairwise comparisons between cities indicated that
      NO(2)(-) and NO(3)(-) contents of all C type products were not appreciably
      different, and the same was true for most ONC products. Numerical NO(2)(-) values
      were less variable than NO(3)(-) concentrations within each meat product
      category. NO(2)(-) concentrations were similar to those previously reported by
      Cassens ( Cassens  ,   R. G. Residual nitrite in cured meat .  Food Technol.    
      1997a  ,   51  ,   53 - 55  ) in 1997. Residual NO(2)(-) and NO(3)(-) values in
      this study were numerically lower than those reported by NAS ( National Academy
      of Sciences .   The Health Effects of Nitrate, Nitrite, and N-Nitroso Compounds ;
      National Academy Press :  Washington, DC ,    1981  ) in 1981. Data from this
      survey provide a benchmark of NO(2)(-) and NO(3)(-) concentrations for ONC
      products available at retail.

PMID- 22414375
TI  - Energy restriction and the prevention of breast cancer.
AB  - Energy restriction (ER) to control weight is a potential strategy for breast
      cancer prevention. The protective effects of habitual continuous energy
      restriction (CER) and weight loss on breast tumour formation have been
      conclusively demonstrated in animal studies over the past 100 years, and more
      recently in women using data from observational studies and bariatric surgery.
      Intermittent energy restriction (IER) and intermittent fasting (IF) are possible
      alternative preventative approaches which may be easier for individuals to
      undertake and possibly more effective than standard CER. Here, we summarise the
      available data on CER, IER and IF with special emphasis on their potential for
      breast cancer prevention. In animals, IER is superior or equivalent to CER with
      the exception of carcinogen-induced tumour models when initiated soon after
      carcinogen exposure. There are no human data on IER and breast cancer risk, but
      three studies demonstrated IER and CER to be equivalent for weight loss. IF
      regimens also reduce mammary tumour formation in animal models and also led to
      weight loss in human subjects, but have not been directly compared with CER.
      Animal and some human data suggest that both IER and IF may differ
      mechanistically compared with CER and may bring about greater reduction in
      hepatic and visceral fat stores, insulin-like growth factor 1 (IGF-1) levels and
      cell proliferation, and increased insulin sensitivity and adiponectin levels.
      Although IER and IF were first studied 65 years ago, we conclude that further
      studies are required to assess their values compared with CER.

PMID- 22414378
TI  - Reproducibility and intraindividual variation over days in buccal cell DNA
      methylation of two asthma genes, interferon gamma (IFNgamma) and inducible nitric
      oxide synthase (iNOS).
AB  - The biological mechanisms responsible for the onset and exacerbation of asthma
      symptoms in children may involve the epigenetic regulation of inflammatory genes
      after environmental exposures. Using buccal cells, we hypothesized that DNA
      methylation in promoter regions of two asthma genes, inducible nitric oxide
      synthase (iNOS) and interferon gamma (IFNgamma), can vary over several days.
      Repeat buccal samples were collected 4 to 7 days apart from 34 children
      participating in the Columbia Center for Children's Environmental Health (CCCEH)
      birth cohort study. Several field duplicates (sequential collection of two
      samples in the field) and replicates (one sample pyrosequenced twice) also were
      collected to ensure consistency with collection and laboratory procedures. DNA
      methylation was assessed by pyrosequencing a PCR of bisulfite-treated DNA. We
      found that replicate and field duplicate samples were correlated strongly (r =
      0.86 to 0.99, P < 0.05), while repeat samples demonstrated low within-subject
      correlations (r = 0.19 to 0.56, P = 0.06 to 0.30). Our data reveal DNA
      methylation as a dynamic epigenetic mechanism that can be accessed safely and
      reproducibly in an inner city pediatric cohort using non-invasive buccal swabs
      and pyrosequencing technology.

PMID- 22414377
TI  - Protein degradation and the stress response.
AB  - Environmental stresses are manifold and so are the responses they elicit. This is
      particularly true for higher eukaryotes where various tissues and cell types are
      differentially affected by the insult. Type and scope of the stress response can
      therefore differ greatly among cell types. Given the importance of the ubiquitin
      proteasome system (UPS) for most cellular processes, it comes as no surprise that
      the UPR plays a pivotal role in counteracting the effects of stressors. Here we
      outline contributions of the UPS to stress sensing, signaling, and response
      pathways. We make no claim to comprehensiveness but choose selected examples to
      illustrate concepts and mechanisms by which protein modification with ubiquitin
      and proteasomal degradation of key regulators ensures cellular integrity during
      stress situations.

PMID- 22414379
TI  - Clinical correlates of atypical femoral fracture.
AB  - BACKGROUND: Reports of atypical femur fracture in bisphosphonate-exposed women
      have prompted interest in characterizing the clinical profiles of these patients.
      METHODS: Among women age >=60 years with hip or femur fracture during 2007-2008,
      we identified 79 with low-trauma subtrochanteric or femoral shaft fracture.
      Radiographic images were reviewed to assign fracture pattern and distinguish
      atypical femur fracture from non-atypical femur fracture. Differences in clinical
      characteristics and pharmacologic exposures were compared. RESULTS: Among 79
      women (38 subtrochanteric and 41 femoral shaft fracture), 38 had an atypical
      femur fracture. Compared to those with a non-atypical femur fracture, women with
      atypical femur fracture were significantly younger (74.0 vs 81.0 years), more
      likely to be Asian (50.0 vs 2.4%) and to have received bisphosphonate therapy
      (97.4 vs 41.5%). Similarly, the contralateral femur showed a stress or complete
      fracture in 39.5% of atypical femur fractures vs 2.4% non-atypical femur
      fracture, and focal cortical hypertrophy of the contralateral femur in an
      additional 21.1% of atypical cases. CONCLUSIONS: Women suffering atypical femur
      fractures have a markedly different clinical profile from those sustaining
      typical fractures. Women with atypical femur fracture tend to be younger, Asian,
      and bisphosphonate-exposed. The high frequency of contralateral femur findings
      suggests a generalized process.

PMID- 22414380
TI  - Enhanced fungal DNA-extraction from formalin-fixed, paraffin-embedded tissue
      specimens by application of thermal energy.
AB  - Determining the etiology of invasive fungal infections (IFI) is critical for
      patient management as fungi vary in their susceptibility to antifungals. However,
      the etiology remains obscure in many cases due to negative culture results. The
      identification of fungal DNA by PCR in pathology blocks and sequencing it is an
      alternative approach to determine the cause of IFI. Previous studies identified
      fungal DNA in only 50% of samples with positive histopathology results, probably
      due to DNA damage by tissue fixation. We used realtime PCR to quantify human and
      fungal DNA from formalin-fixed, paraffin-embedded tissue specimens in order to
      study the effect of thermal energy during extraction on the yield of amplifiable
      DNA and subsequent identification of fungal DNA. Tissue sections from eight
      patients with proven IFI were subjected to DNA extraction with varying exposure
      to thermal energy. Amplifiable DNA increased up to 76-fold by increasing the
      incubation temperature from 65 degrees C to 90 degrees C and an additional
      increase was documented by incubating samples for up to 6 hours at this
      temperature. The augmented amplification of fungal DNA was associated with
      improved species identification by the sequencing of the PCR amplicons. This may
      help illuminate the etiology of IFI and thereby improve patient management by
      guiding antifungal therapy.

PMID- 22414381
TI  - Study on sexual and reproductive health behaviors of unmarried female migrants in
      China.
AB  - AIM: The purpose of this study was to broadly assess the level of knowledge,
      attitude and behaviors related to sexual and reproductive health (SRH) among
      unmarried female migrants in China. MATERIAL AND METHODS: This cross-sectional
      study was conducted and a self-administered questionnaire was designed for
      collecting information on SRH including 15 items for knowledge, 8 items for
      attitude and some items for contraception and abortion related behaviors.
      RESULTS: A total of 1690 unmarried female migrants were interviewed. Most of the
      respondents had less knowledge of SRH. Only one-third of respondents was aware of
      emergency contraceptives and could freely talk about SRH with their friends. Over
      one-third of respondents were not willing to come into contact with someone with
      AIDS or STDs. In this study, 10.4% participants had an unwanted pregnancy and 95%
      of them had an abortion. Multivariate analysis showed that having a boyfriend,
      duration of employment in city, knowledge on SRH and freely discussing SRH with
      peer were associated with having premarital sex among these unmarried female
      migrants. CONCLUSION: This study revealed that the unmarried female migrant was
      one of the most vulnerable groups concerning SRH. In some policy reforms,
      appropriate and cost-effective SRH services should be provided for these
      migrants.

PMID- 22414382
TI  - Stereoselective dissipation of epoxiconazole in grape (Vitis vinifera cv. Kyoho)
      and soil under field conditions.
AB  - Stereoselective dissipation of epoxiconazole had been studied in grape and soil
      during plant growing under field conditions in this paper. A sensitive and rapid
      chiral method was developed and validated for the determination of epoxiconazole
      stereoisomers in grape and soil based on liquid chromatography coupled with
      triple quadrupole mass spectrometry (LC-MS/MS). Phenomenex Lux Cellulose-1 column
      was used for enantioseparation with a mixture of acetonitrile/water (90/10, v/v)
      as mobile phase at flow rate of 0.3 mL min(-1). Fortified recoveries in grape and
      soil samples ranged from 76.0% to 91.9% and relative standard deviations were
      less than 11.4% with fortified levels of 0.025-1.0 mg kg(-1). The limits of
      detection and quantification were 0.005 mg kg(-1) and 0.025 mg kg(-1),
      respectively, with linear calibration curves extending up to 5.0 mg kg(-1). The
      field experimental results showed that dissipations of epoxiconazole
      stereoisomers in grape followed first-order kinetics (R(2)>0.92) and
      stereoselectivity occurred in 2 h after spraying. The (-)-stereoisomer with half
      life of 9.3 d degraded faster than (+)-stereoisomer with that of 13.2 d, and
      resulted in relative enrichment of (+)-stereoisomer. However, the stereoisomeric
      dissipations in soil were triphasic ("increase-decrease-steady") with lower
      dissipation rates, and also occurred with preferential degradation of (-)
      stereoisomer under field condition. The results for stereoselective dissipations
      can be applied for food and environmental assessments of chiral pesticides.

PMID- 22414383
TI  - Diabetic retinopathy screening: perspectives of people with diabetes, screening
      intervals and costs of attending screening.
AB  - AIMS: To obtain the views of people with diabetes about the provision of diabetic
      retinopathy screening services; and the interval of screening. METHODS: Between
      October 2009 and January 2010, people with diabetes attending diabetic
      retinopathy screening clinics across Wales were asked to complete a questionnaire
      comprising of two parts: the first asking about their health, diabetes history,
      demographic characteristics and views about the diabetic retinopathy screening
      service, and the second asking about the costs of attending the screening.
      RESULTS: The response rate was 40% (n = 621) from 1550 questionnaires distributed
      at diabetic retinopathy clinics, with 600 complete responses analysed.
      Respondents had a mean known duration of diabetes of 8.5 years (sd 7.8) and had
      attended for screening on average 3.2 times (sd 1.6) in the last 5 years. Sixty
      eight per cent (n = 408) of respondents reported having their eyes screened
      approximately once a year. Eighty-five per cent (n = 507) felt that they should
      have their eyes screened every year. However, 65% (n = 390) of respondents would
      accept screening at 2- or 3-year intervals if medical evidence showed that it was
      safe. The reported personal costs incurred by respondents attending diabetic
      retinopathy screening were low. CONCLUSION: Our study suggests that people with
      diabetes undergoing diabetic retinopathy screening would accept a greater
      screening interval, provided that adequate clinical evidence and medical
      reassurance were given.

PMID- 22414384
TI  - Polyethylene glycosylation prolongs the stability of recombinant human
      paraoxonase-1.
AB  - Paraoxonase-1 (PON1) is a native enzyme that is synthesized in the liver and is
      capable of hydrolyzing organophosphates (OPs). It is regarded as part of a
      promising approach for the pretreatment and therapy of OP poisoning. Previous
      experiments with purified rabbit serum PON1 have established that it can protect
      rats against many OP exposures. In the current paper, we described a preparation
      of active recombinant human PON1 (rHuPON1) by engineering an Escherichia coli
      expression system. Recombinant HuPON1 was purified by Ni-NTA affinity
      chromatography followed by DEAE sepharose fast-flow chromatography. After
      purification, rHuPON1 was chemically modified with polyethyleneglycol (PEG)-20K.
      Recombinant HuPON1 exhibited a mean residence time (MRT) of 8.9h, which was
      threefold shorter than that of native HuPON1 in rats. However, rHuPON1 chemically
      modified with PEG-20K displayed an MRT of 19.5h, suggesting that PEG modification
      can prolong the circulatory stability of rHuPON1. PEG-rHuPON1 had a catalytic
      efficiency sufficient in protecting rats against OP poisoning, as measured by
      acetylcholinesterase activity in tissues and signs after poisoning.

PMID- 22414385
TI  - In vivo hydroquinone exposure causes tracheal hyperresponsiveness due to TNF
      secretion by epithelial cells.
AB  - Hydroquinone (HQ) is the main oxidative substance in cigarette smoke and a toxic
      product of benzene biotransformation. Although the respiratory tract is an inlet
      pathway of HQ exposure, its effect on airway muscle responsiveness has not been
      assessed. We thus investigated the effects of low dose in vivo HQ-exposure on
      tracheal responsiveness to a muscarinic receptor agonist. Male Swiss mice were
      exposed to aerosolised 5% ethanol/saline solution (HQ vehicle; control) or 0.04
      ppm HQ (1h/day for 5 days) and tracheal rings were collected 1h after the last
      exposure. HQ exposure caused tracheal hyperresponsiveness to methacholine (MCh),
      which was abolished by mechanical removal of the epithelium. This
      hyperresponsiveness was not dependent on neutrophil infiltration, but on tumour
      necrosis factor (TNF) secretion by epithelial cells. This conclusion was based on
      the following data: (1) trachea from HQ-exposed mice presented a higher amount of
      TNF, which was abrogated following removal of the epithelium; (2) the trachea
      hyperresponsiveness and TNF levels were attenuated by in vivo chlorpromazine
      (CPZ) treatment, an inhibitor of TNF synthesis. The involvement of HQ-induced TNF
      secretion in trachea mast cell degranulation was also demonstrated by the partial
      reversion of tracheal hyperresponsiveness in sodium cromoglicate-treated animals,
      and the in vivo HQ-exposure-induced degranulation of trachea connective tissue
      and mucosal mast cells, which was reversed by CPZ treatment. Our data show that
      in vivo HQ exposure indirectly exacerbates the parasympathetic-induced
      contraction of airway smooth muscle cells, mediated by TNF secreted by tracheal
      epithelial cells, clearly showing the link between environmental HQ exposure and
      the reactivity of airways.

PMID- 22414387
TI  - Lyophilised ready-to-use formulations of PEG-PCL-PEI nano-carriers for siRNA
      delivery.
AB  - The purpose of the present study was to transfer aqueous PEG-PCL-PEI nano
      suspensions into dry ready-to-use formulations, suitable for delivery of siRNA.
      Therefore, freshly prepared nano-suspensions were lyophilised with glucose as
      lyoprotectant. Firstly, the required glucose concentration for sufficient
      stabilisation of unloaded carriers was determined via dynamic light scattering.
      Morphology of fresh and rehydrated carriers was visualised by cryogenic scanning
      electron microscopy. Subsequently, the feasibility of siRNA loading before and
      after lyophilisation was investigated. For both strategies complex diameter and
      in vitro transfection efficiency were determined and correlated to freshly
      prepared samples. Hydrodynamic diameter (95.2 +/- 1.4 nm) and size distribution
      (0.132 +/- 0.019) of unloaded nano-suspension were restored after rehydration by
      addition of >= 1.5% of glucose before lyophilisation. Moreover, after loading of
      rehydrated carriers with siRNA, no significant difference in complex size was
      observed as compared to freshly prepared ones. Stabilisation of pre-formed
      carrier/siRNA complexes during lyophilisation is feasible at elevated N/P (e.g.
      20) and glucose concentrations above 5%. As determined via real-time-PCR,
      lyophilised samples were as active as freshly prepared ones regarding
      transfection efficiency. In conclusion, lyophilisation is an effective technique
      to produce physically stable PEG-PCL-PEI formulations. These general findings may
      be applicable to further particulate gene delivery systems to shelf ready-to-use
      formulations.

PMID- 22414386
TI  - Pharmacologic ER stress induces non-alcoholic steatohepatitis in an animal model.
AB  - Endoplasmic reticulum (ER) stress refers to a condition of accumulation of
      unfolded or misfolded proteins in the ER lumen, which is known to activate an
      intracellular stress signaling termed Unfolded Protein Response (UPR). A number
      of pharmacologic reagents or pathophysiologic stimuli can induce ER stress and
      activation of the UPR signaling, leading to alteration of cell physiology that is
      associated with the initiation and progression of a variety of diseases. Non
      alcoholic steatohepatitis (NASH), characterized by hepatic steatosis and
      inflammation, has been considered the precursor or the hepatic manifestation of
      metabolic disease. In this study, we delineated the toxic effect and molecular
      basis by which pharmacologic ER stress, induced by a bacterial nucleoside
      antibiotic tunicamycin (TM), promotes NASH in an animal model. Mice of C57BL/6J
      strain background were challenged with pharmacologic ER stress by intraperitoneal
      injection of TM. Upon TM injection, mice exhibited a quick NASH state
      characterized by hepatic steatosis and inflammation. An increase in hepatic
      triglycerides (TG) and a decrease in plasma lipids, including plasma TG, plasma
      cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL),
      were observed in the TM-treated mice. In response to TM challenge, cleavage of
      sterol responsive binding protein (SREBP)-1a and SREBP-1c, the key trans
      activators for lipid and sterol biosynthesis, was dramatically increased in the
      liver. Consistent with the hepatic steatosis phenotype, expression of some key
      regulators and enzymes in de novo lipogenesis and lipid droplet formation was up
      regulated, while expression of those involved in lipolysis and fatty acid
      oxidation was down-regulated in the liver of mice challenged with TM. Moreover,
      TM treatment significantly increased phosphorylation of NF-kappaB inhibitors
      (IkappaB), leading to the activation of NF-kappaB-mediated inflammatory pathway
      in the liver. Our study not only confirmed that pharmacologic ER stress is a
      strong "hit" that triggers NASH, but also demonstrated crucial molecular links
      between ER stress, lipid metabolism, and inflammation in the liver in vivo.

PMID- 22414388
TI  - Solid dispersions of itraconazole for inhalation with enhanced dissolution,
      solubility and dispersion properties.
AB  - The purpose of this study was to produce a dry powder for inhalation (DPI) of a
      poorly soluble active ingredient (itraconazole: ITZ) that would present an
      improved dissolution rate and enhanced solubility with good aerosolization
      properties. Solid dispersions of amorphous ITZ, mannitol and, when applicable, D
      alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) were produced by spray
      drying hydro-alcoholic solutions in which all agents were dissolved. These dry
      formulations were characterized in terms of their aerosol performances and their
      dissolution, solubility and physical properties. Modulate differential scanning
      calorimetry and X-ray powder diffraction analyses showed that ITZ recovered from
      the different spray-dried solutions was in an amorphous state and that mannitol
      was crystalline. The inlet drying temperature and, indirectly, the outlet
      temperature selected during the spray-drying were critical parameters. The outlet
      temperature should be below the ITZ glass transition temperature to avoid severe
      particle agglomeration. The formation of a solid dispersion between amorphous ITZ
      and mannitol allowed the dry powder to be produced with an improved dissolution
      rate, greater saturation solubility than bulk ITZ and good aerosol properties.
      The use of a polymeric surfactant (such as TPGS) was beneficial in terms of
      dissolution rate acceleration and solubility enhancement, but it also reduced
      aerosol performance. For example, significant dissolution rate acceleration
      (f(2)<50) and greater saturation solubility were obtained when introducing 1%
      (w/w) TPGS (mean dissolution time dropped from 50.4 min to 36.9 min and
      saturation solubility increased from 20 +/- 3 ng/ml to 46 +/- 2 ng/ml). However,
      the fine particle fraction dropped from 47 +/- 2% to 37.2 +/- 0.4%. This study
      showed that mannitol solid dispersions may provide an effective formulation type
      for producing DPIs of poorly soluble active ingredients, as exemplified by ITZ.

PMID- 22414390
TI  - Fecal glucocorticoid response to environmental stressors in green iguanas (Iguana
      iguana).
AB  - Quantification of glucocorticoid metabolites in feces has been shown to be a
      powerful tool in evaluating well-being in vertebrates. Little is known however
      about the hypothalamic-pituitary-adrenal axis response to stressors, and
      consequent glucocorticoid excretion, in reptiles. In a longitudinal study, fecal
      corticosterone metabolite (FCM) levels in green iguanas (Iguana iguana) were
      quantified during periods of rest and exposure to hypothesized stressors. FCM
      quantification was combined with behavioral analysis to further contextualize the
      measured increases. It was shown that both daily 5-minute handling/restraint, as
      well as housing devoid of climbing opportunity, resulted in increased FCM
      excretion. Behavioral analysis suggested that the iguanas were chronically
      stressed by the lack of climbing opportunity, whereas handling may have induced
      only a transient stress response. The experimental design, using repeated periods
      of stressor-exposure, also revealed a facilitating effect, where the two
      stressors potentiated one another. Furthermore, the order of the two stressors
      was found to be important. The study provides insight into the functioning of the
      hormonal stress response in green iguanas, and to the refining of their housing
      and handling.

PMID- 22414389
TI  - Structural characterization of the lignin in the cortex and pith of elephant
      grass (Pennisetum purpureum) stems.
AB  - The structure of the lignin in the cortex and pith of elephant grass (Pennisetum
      purpureum) stems was studied both in situ and in isolated milled "wood" lignins
      by several analytical methods. The presence of p-coumarate and ferulate in the
      cortex and pith, as well as in their isolated lignins, was revealed by pyrolysis
      in the presence of tetramethylammonium hydroxide, and by 2D NMR, and indicated
      that ferulate acylates the carbohydrates while p-coumarate acylates the lignin
      polymer. 2D NMR showed a predominance of alkyl aryl ether (beta-O-4') linkages
      (82% of total interunit linkages), with low amounts of "condensed" substructures,
      such as resinols (beta-beta'), phenylcoumarans (beta-5'), and spirodienones (beta
      1'). Moreover, the NMR also indicated that these lignins are extensively acylated
      at the gamma-carbon of the side chain. DFRC analyses confirmed that p-coumarate
      groups acylate the gamma-OHs of these lignins, and predominantly on syringyl
      units.

PMID- 22414391
TI  - [Alteration of the state general or alteration of the clinical relevance?].

PMID- 22414392
TI  - [Pastel in the urine bag].
AB  - Purple urine bag syndrome is a relatively unknown phenomenon in which the urine
      bag and the collector of chronically catheterized patients turn purple or blue.
      It affects predominantly women, and is mainly reported in elderly patients. The
      mechanism seems to be related to the appearance in the urine of two compounds
      that have been identified as indigo (blue) and indirubin (red) which bind to the
      urine bag and the collector. Several associated factors are usually mentioned
      such as constipation, alkaline urine, bed rest, institutionalization or cognitive
      impairment. They are risk factor of this phenomenon. On the other hand, an
      infection or a urinary bacterial colonization is necessary and high bacterial
      counts seem to be the critical step in the development of the purple urine bag
      syndrome. We report on two cases of purple urine bag syndrome observed in two
      patients being treated in a long-term care unit. Both of whom were diagnosed with
      indwelling urinary bacterial colonization, with Escherichia coli and Pseudomonas
      aeruginosa respectively.

PMID- 22414393
TI  - [Adequacy to the recommendations in urinary tract infections: a multicenter
      transversal survey in hospitalized patients aged over 75 years].
AB  - French diagnostic and therapeutic recommendations about UI were built-up in 2008.
      We studied clinician's practices and evaluated the adequacy to the
      recommendations in hospitalized patients aged over 75 years. METHOD: Multicenter
      survey in acute care of geriatric, internal medicine and infectious disease
      wards. During one week, all positive urine cultures of patients over 75 were
      reported to the local investigator who had to fill out a questionnaire. The data
      specified the final diagnosis: cystitis, pyelonephritis, prostatitis, or
      colonization, the antibiotic treatment, the re-evaluation after 72 hours of
      treatment, the association with another infectious diagnosis and the radiological
      examinations performed. RESULTS: 241 questionnaires were collected from 48 wards.
      Colonization, cystitis, pyelonephritis and prostatitis were diagnosed
      respectively in 42, 27, 20 and 11% of urine cultures. In 48% of cystitis cases,
      the duration of treatment was inadequate. In 77% cases of pyelonephritis, the
      antibiotic was adapted to the recommendations, but 44% of patients had no further
      radiological examination. In cases of prostatitis antibiotic therapy was adequate
      in 74% of cases but often with a non-conform duration of treatment (56%) and
      absence of further radiographic examination (70%). The reassessment of the
      treatment at day 3 ranged from 63 to 88%. In 26% of UI diagnosis, another
      associated infection was described, mainly bronchopneumonia (56%). CONCLUSION:
      Progress is needed to optimize treatment revaluation at 72 hours and adequate
      duration of treatment. The association of UI and bronchopneumonia is
      questionable. More specific recommendations would probably be useful to optimize
      the management of UI in the elderly.

PMID- 22414394
TI  - [Botulinum toxin in the elderly to the care of limbs spastic hypertonia and toes
      or fingers dystonias].
AB  - OBJECTIVE: To show the botulinum toxin interest and limits in the elderly
      presenting a limbs spastic hypertonia and/or a dystonia, through a clinical study
      and a literature review. METHOD: We report a 6 years and 8 months retrospective
      single center study, concerning 49 patients, all of them was more than 70 years
      old and had received one or several botulinum toxin injections for a limbs
      spastic hypertonia and/or a dystonia. RESULTS: The population average was 76,9
      years old (70 to 92 years old). It was possible to realize several sessions for
      the same patient if respecting a three months interval between two sessions. No
      major side effects was noticed. More than half of the patients felt a significant
      improvement of their life quality, their functional status and/or on pain. A
      multidisciplinary care was systematically associated with the botulinum toxin.
      CONCLUSION: The botulinum toxin is an additional asset for the spasticity care of
      the geriatric patient in rehabilitation, if indications and contraindications are
      advisedly targeted. The age cannot be considered as a limitating factor.

PMID- 22414395
TI  - [Analysis of iatrogenic risk related to anticholinergic effects using two scales
      in acute geriatric inpatient unit].
AB  - Anticholinergic medications are responsible for most frequent adverse drug
      effects. Two scales have been elaborated as tools for prescribers: the
      Anticholinergic Drug Scale (ADS) of Carnahan et al., and the Anticholinergic Risk
      Scale (ARS) of Rudolph et al. The objective of this study was to analyze the
      diagnostic performance of both scales for predicting signs related to an
      anticholinergic effect. METHOD: Medical records of 1379 patients aged 75 years or
      older hospitalized in a geriatric acute care unit between 2002 and 2005 were
      studied. The analyze was made retrospectively, but data were collected
      prospectively. RESULTS: Risk of appearance of total anticholinergic signs (ADS :
      OR 1,45, CI 95% [1,03-2,03], p=0,037 and ARS : OR 1,98, CI 95% [1,19-3,28]
      p<0,01) and peripheral signs (ADS: OR 1,66, CI 95% [1,22-2,26], p<0,01 and ARS :
      OR 1,81, CI 95% [1,19-2,75], p<0,01) increased when score was >= 3 with both
      scales, which wasn't the case for central signs. CONCLUSION: Both scales
      permitted to detect an increased risk of appearance of total and peripheral
      anticholinergic signs, but not the centrals as delirium. Interest of total
      anticholinergic burden remains to be demonstrated, especially for delirium risk
      assessment.

PMID- 22414396
TI  - [Deterioration of general condition: a "geriatric syndrome"?].
AB  - INTRODUCTION: Deterioration of general condition (DGC) is a common cause of
      admission in geriatrics. Except some French textbooks which define DGC as a
      clinical pattern that associates asthenia, anorexia and wheigt loss, we did not
      find a consensus to define this entity. OBJECTIVES: To assess the clinical
      pattern that covers DGC as a cause of admission in an acute geriatric unit.
      METHODS: Analyse of 747 medical charts of patients consecutively admitted between
      April 2006 and September 2008. The admission's complaints of patients were
      identified with a particular focus on the triad asthenia, anorexia and weight
      loss. RESULTS: Two hundred eleven patients (28%) were admitted during this period
      for DGC. Among them, 38% had at least one of the complaints that characterizes
      the concept of DGC (asthenia, anorexia, weight loss), 2% had three complaints, 8%
      had at least two and 28% one. Among patients referred for DGC, 45% were admitted
      for one or more geriatric problems and 53% for complaints of medico-surgical
      condition. DISCUSSION: The lack of consistency in the clinical picture of
      patients admitted for DGC does not say whether it's a real syndrome. In
      geriatrics, however it could represent an expression of frailty.

PMID- 22414397
TI  - [Estimate of the prevalence of cognitive impairment in an elderly population of
      the health center of Senegalese national retirement institution].
AB  - OBJECTIVE: To assess the prevalence of cognitive impairment in a Senegalese
      elderly population, of the Sociohealth and university center of Senegalese
      national retirement institution, Dakar, Senegal. METHODOLOGY: A cross sectional
      study was conducted in 872 Senegalese elderly population aged 55 years and over
      utilizing the Sociohealth and university center of IPRES, Dakar, Senegal for
      health care. Sociodemographic, lifestyles, physical activity, medical history,
      familial history of dementia data were collected with a structured questionnaire
      completed with a clinical exam and neuropsychological testing. Cognitive
      impairment was defined as a score of 28 or less with the test of Senegal.
      RESULTS: Ninety four subjects (10.8%; 95% CI 8,7-12,9) had cognitive impairment.
      Mean age was 67.2 years (+/-7.5 years), 63% were men, 79% were married, and half
      of them knew how to read and write. Hypertension, arthritis and gastro-intestinal
      diseases were the main health conditions reported. Prevalence of cognitive
      impairment varied with age and education. CONCLUSION: Prevalence of cognitive
      decline in the Sociohealth and university center of IPRES, Dakar, Senegal, is
      higher and varied with age and education.

PMID- 22414398
TI  - [Elderly subjects hospitalised in acute care medical unit: baseline date and on
      year follow-up].
AB  - OBJECTIVES: To describe the elderly population hospitalized in a service of short
      term care, and to follow during one year its evolution in term of dependence and
      of rehospitalisation. METHODS: Inclusion of all the patients of more than 75
      years hospitalized in the service during 5 weeks, with initial geriatric
      evaluation, and phone evaluation in 6 months and one year. RESULTS: Seventy-four
      patients were included, among which 57 were living at home. The mean length of
      stay was 11 days. In one year, 22 patients died, 23 went in institution and 29
      are always in the place of residence, among which 18 with a rise of the helps.
      53% of patients were rehospitalized at least once. CONCLUSION: This work allows a
      description, social and functional, of the patients older than 75 years,
      hospitalized in the service. It confirms the risk of loss of autonomy and of
      unplanned readmission, in the short and medium term, that a geriatric program
      could limit.

PMID- 22414399
TI  - [Emotions and lateral sclerosis].

PMID- 22414400
TI  - [Emotions and amyotrophic lateral sclerosis: a psychopathological perspective].
AB  - Emotions have not often been studied in amyotrophic lateral sclerosis (ALS). Most
      existing studies have assessed the psychopathological manifestations involved,
      essentially depression and less frequently anxiety. The results have shown that
      major depressive episodes and anxious episodes are not frequent in ALS patients,
      although moderate depressive or anxious symptoms are often observed, but less
      frequently than in other diseases like multiple sclerosis or Parkinson's disease.
      Depressive symptoms are not correlated to the duration or severity of the
      disease. This has led us to investigate the coping mechanisms involved in ALS.
      Results of previously published studies have shown that they did not differ from
      those observed in other somatic diseases, but ALS patients show more frequent
      concern with spirituality and religious preoccupations. It thus appears necessary
      to make a more detailed study of how ALS patients cope with the disease and its
      ominous consequences. Emotional processing difficulties may be a factor
      underlying quite diverse somatic and psychological disorders. The Baker's model
      propose five stages in emotional processing: emotional experience, emotional
      expression, labelling, linkage and awareness. Assessment of the emotional
      processing used by ALS patients should improve our comprehension of their
      adaptive functioning. The patients' caregivers play an essential role, and
      studies have shown that they often suffer themselves from depression and the
      burdens involved, and that the perceived social support has an impact on the
      quality of life and on the depression of the patients. Therefore, it seems
      important to assess the emotional processing not only of patients but also of
      their caregivers.

PMID- 22414401
TI  - [Alzheimer's disease and related disorders: specificity of young onset patients,
      including ethical aspects].
AB  - The number of patients with young onset dementia (YOD) (that is before age 65) is
      estimated at 32,000 in France, and 5000 with onset dementia before 60 years.
      These patients differ from older ones by the greater number of rares causes
      (29%), heterogeneity of the presentation among the usual diseases, such as non
      amnestic phenotypes of Alzheimer's disease, high frequency of frontal symptoms,
      and possible genetic origin. These aspects must be taken into account for the
      diagnosis, often more difficult than in older ones because patients have a little
      knowledge of the YOD, excepted in the genetics forms. YOD patients can still work
      or drive a car, and we should choose between the respect for autonomy and the
      security for the patient and their carers. YOD patients can be more often
      included in pharmacological trials because they have lower associated disorders.
      Individual non-pharmacological treatment should be priviledged because they don't
      easily accept collective activities with other patients over 60 years of age.
      Excepted for the very young patients (onset before 45), the survival is longer
      than in late onset dementia, with sometimes severe behavioral problems related to
      frontal syndrome. In France, the caregiving at home has been improved since the
      possibility for the YOD patients to receive a financial assistance reserved for
      the disabled patients, but admission to a nursing home before 60 is very
      difficult and increases the caregiver burden and perception of unfairness. There
      is a discrimination between young or older demented patients related to the great
      difficulty to meet the needs of younger patients, due to the rigidity of the
      medical and social systems. The presentation of a limited offer for the YOD
      patients must initiate reflections on our capacities to respect the autonomy and
      the dignity of the Alzheimer's patients regardless of age.

PMID- 22414402
TI  - [For an integrative approach of Alzheimer's disease. Relevance and limits].
AB  - Alzheimer's disease could be studied according to neurological, cognitive, and
      psychopathological aspects. We propose an integrative approach fitting together
      the theoretical advances of the various dimensions to develop a better
      understanding of the disorders, then a better care for the patients. The
      integrative approach deviates deliberately from any attempt to formulate
      etiological hypotheses, and considers the disorder in its functional complexity,
      simultaneously taking into account the somatic and psychological factors
      involved. According to this monistic view, the traditional cleavage between the
      soma and psyche, usually found in Alzheimer's disease, should be rejected and
      substituted for the principle of compatibility intending to identify the points
      of convergence of various conceptual approaches in order to emphasize their
      potential overlap and areas of clinical complementarity rather than their
      epistemological antagonisms. The neuro-psychic link is therefore central to the
      conceptual development proposed here, and more specifically for the memory
      disorders, the concept of memory trace belonging both to psychoanalytic and
      neuropsychological theories.

PMID- 22414403
TI  - [The effects of video games on cognitive aging].
AB  - Advancing age is associated with cognitive decline, which, however, remains a
      very heterogeneous phenomenon. Indeed, several extrinsic factors seem to modulate
      the effect of aging on cognition. Recently, several studies have provided
      evidence that the practice of video games could engender many benefits by
      favoring the maintenance of cognitive vitality in the elderly. This review of the
      literature aims to establish a precise inventory of the relations between the
      various types of video games and cognitive aging, including both sedentary video
      games (i.e., classics as well as brain training) and active video games (i.e.,
      exergames). The largest benefits seem to be provided by exergames which combine
      game play with significant physical exercise. This article also tries to define
      the determinants of the training programs which could be responsible for the
      observed improvements.

PMID- 22414404
TI  - [What about the mental time travel and age-related effects?].
AB  - According to Tulving, episodic memory allows humans to travel mentally through
      subjective time into either the past or the future, this ability being at the
      origin of adaptation, organization and planning of future behavior. The main aim
      of this review is to present a state of art of episodic mental time travel and a
      lifespan perspective from children to elderly people. We examine the numerous
      similarities between remembering the past and envisioning the future which have
      been highlighted in cognitive, neuroimaging, and neuropsychological studies. We
      also present studies that have given evidence that remembering the past and
      imagining the future differ somewhat. We focus on demonstrating that hippocampal
      dysfunction is associated with disturbances in the recall of episodic
      autobiographical details in past memories, but also in the imagining of episodic
      detailed future events. More specifically, we discuss that the future seems to
      involve higher semantic processes mediated by the inferior frontal and lateral
      temporal gyri. We propose that the study of mental travel in personal time could
      be undertaken in line with the distinction between the memory of (episodic)
      experiences and (semantic) personal knowledge of one's life, which constitutes a
      major part of the self and constraints what we have been, what we are now, and
      what we might yet become.

PMID- 22414405
TI  - [Apathy in frontotemporal dementia and Alzheimer's disease: are there distinct
      profiles?].
AB  - OBJECTIVE: To find out if distinct clinical profiles of apathy can be
      distinguished in frontotemporal dementia (FTD) and Alzheimer's disease (AD).
      SUBJECTS: 13 outpatients with the frontal variant of DFT, 36 with AD and 29
      control subjects. METHODS: The scores of the Apathy evaluation scale, AES
      (Marin), filled in by close relatives, were compared to a) cognitives measures,
      including global ratings (Mini mental state, Dementia rating scale), and specific
      assessments for memory (Selective reminding test), inhibition (Stroop test) and
      planification (6 elements); b) affective measures for depression (Montgomery and
      Asberg, and Hamilton depression rating scales), emotional disturbances (Abrams
      and Taylor scale, ATS; Depression mood scale, DMS), assessment of valence and
      intensity of affective reactions by the International affective picture system,
      IAPS), dimensions of personality (NEO PI-R, Defensive style questionnaire, DSQ);
      c) functional assessment: Self-maintenance physical scale (ADL) and Instrumental
      activities of daily living (Lawton), Social activities scale (Katz and Lyerly),
      and Disability assessment for dementia, DAD. Apathy was also assessed by the
      Neuropsychiatric Inventory (NPI) and a new tool, the Goal-directed activities
      scale (GDAS), which allows a quantitative assessment of 32 goal-directed
      activities and a qualitative evaluation of 4 causal attributions: E = related to
      external factors; M = disease related; C = affective disturbance related; and D =
      lack of motivation. RESULTS: A close relationship was found between AES scores
      and global cognitive deficits in FTD and AD, but only in AD for the memory and
      executive tests. No relationship was found with the depression scales or
      dimensions of personality. A significant relationship was found both in FDT and
      AD with blunted affect as assessed by ATS, but not with direct assessment by the
      DMS or reactions to the IAPS. Functional activities were closely related to AES
      scores in all evaluations, except for ADL score in FTD. Causal attributions were
      mainly related to lack of motivation in FTD (60% of cases according to the
      patients, and 85% according to the spouses), and both to affective disturbances
      (respectively in 36 and 48% of cases) and lack of motivation (33% and 45%) in AD.
      CONCLUSION: No distinct cognitive or emotional profiles of apathy could be found
      in FTD and AD. Apathy was constant, more severe, and mainly related to lack of
      motivation in FTD, less constant, less severe in AD, and related both to
      affective disturbances and lack of motivation.

PMID- 22414406
TI  - HIV testing and willingness to get HIV testing at a peer-run drop-in centre for
      people who inject drugs in Bangkok, Thailand.
AB  - BACKGROUND: Regular HIV testing among people who inject drugs is an essential
      component of HIV prevention and treatment efforts. We explored HIV testing
      behaviour among a community-recruited sample of injection drug users (IDU) in
      Bangkok, Thailand. METHODS: Data collected through the Mitsampan Community
      Research Project were used to examine correlates of HIV testing behaviour among
      IDU and to explore reasons for not being tested. Multivariate logistic regression
      was used to examine factors associated with willingness to access HIV testing at
      the drug-user-run Mitsampan Harm Reduction Centre (MSHRC). RESULTS: Among the 244
      IDU who participated in this study, 186 (76.2%) reported receiving HIV testing in
      the previous six months. Enrolment in voluntary drug treatment (odds ratio [OR] =
      2.34; 95% confidence interval [CI]: 1.18-4.63) and the tenofovir trial (OR =
      44.81; 95%CI: 13.44-149.45) were positively associated with having been tested,
      whereas MSHRC use (OR = 1.78; 95%CI: 0.96-3.29) was marginally associated with
      having been tested. 56.9% of those who had not been tested reported in engaging
      in HIV risk behaviour in the past six months. 181 (74.2%) participants were
      willing to be tested at the MSHRC if testing were offered there. In multivariate
      analyses, willingness to get HIV testing at the MSHRC was positively associated
      with ever having been to the MSHRC (adjusted odds ratio [AOR] = 2.42; 95%CI: 1.21
      4.85) and, among females, being enrolled in voluntary drug treatment services
      (AOR = 9.38; 95%CI: 1.14-76.98). CONCLUSIONS: More than three-quarters of IDU
      received HIV testing in the previous six months. However, HIV risk behaviour was
      common among those who had not been tested. Additionally, 74.2% of participants
      were willing to receive HIV testing at the MSHRC. These findings provide evidence
      for ongoing HIV prevention education, as well potential benefits of incorporating
      HIV testing for IDU within peer-led harm reduction programs.

PMID- 22414407
TI  - Fluid and electrolyte management for the surgical patient.
AB  - For surgical patients, appropriate selection and administration of fluids can
      mitigate against organ failure, whereas improper dosing can exacerbate already
      injured systems. Fluid and electrolyte goals and deficiencies must be defined for
      individual patients to provide the appropriate combination of resuscitation and
      maintenance fluids. Specific electrolyte abnormalities should be anticipated,
      identified, and corrected to optimize organ functions. Using the strong-ion
      approach to acid-base assessment, delivered fluids that contain calculated
      amounts of electrolytes will interact with the patient's plasma charge and
      influence the patient's pH, allowing the clinician to achieve a more precise end
      point.

PMID- 22414408
TI  - Hypoperfusion, shock states, and abdominal compartment syndrome (ACS).
AB  - Cardiovascular dysfunction and failure are commonly encountered in patients with
      intra-abdominal hypertension or abdominal compartment syndrome. Accurate
      assessment and optimization of preload, afterload, and contractility are
      essential to restoring end-organ perfusion and maximizing patient survival.
      Application of a goal-directed resuscitation strategy, including abdominal
      decompression, when indicated, improves cardiac function, reverses end-organ
      failure, and minimizes intra-abdominal hypertension-related patient morbidity and
      mortality.

PMID- 22414409
TI  - Massive transfusion of blood in the surgical patient.
AB  - Hemorrhage remains a leading cause of morbidity and death in both civilian and
      military trauma. Restoration of effective end-organ perfusion by stopping
      hemorrhage and restoring intravascular volume in such a way as to minimize
      acidosis, hypothermia, and coagulopathy, almost always requires the use of blood
      and/or blood-component therapy. The best method to manage life-threatening
      hemorrhage is to avoid the circumstance that prompted it or to mitigate blood
      loss early in the injury cycle; otherwise, blood replacement must suffice. This
      article reviews current understanding of massive transfusion, along with its
      attendant unintended consequences, in the management of patients with profound
      hemorrhage.

PMID- 22414410
TI  - Postoperative gastrointestinal hemorrhage.
AB  - Significant gastrointestinal (GI) bleeding in the postoperative period is an
      uncommon complication of surgery. The management of GI bleeding within the
      postoperative period is complex because of a larger differential for the source
      of bleeding and a more complex risk/benefit analysis. There is minimal published
      literature specific to the management of postoperative GI bleeding, and the
      infrequency, complexity, and variability of the clinical setting of this
      complication confound simplistic consideration of its cause and therapy. This
      article outlines a systematic evaluation of the patient, treatment options, and
      assessment of risk/benefit ratio for various treatment options.

PMID- 22414411
TI  - Damage control for intra-abdominal sepsis.
AB  - With the success of damage-control surgery for the treatment of exsanguinating
      truncal trauma, it has been adapted to other surgical diseases associated with
      shock states, such as severe secondary peritonitis. The structured approach of
      damage control is easily adapted to and can incorporate the fundamental elements
      of the Surviving Sepsis Campaign. It is not meant to replace tried and true
      surgical principles, such as source control, but is a usable framework in
      managing the complicated circumstances seen with these patients.

PMID- 22414412
TI  - Pathogenesis and clinical and economic consequences of postoperative ileus.
AB  - Postoperative ileus is a preventable disease with surprising economic
      consequences. Understanding the triad of dysmotility in conjunction with an
      enhanced recovery program improves patient outcome, decreases length of stay in
      hospital, and lowers the cost. Alvimopan and other investigational promotility
      medications can help attain these goals. Surgeons should avoid labeling all
      postoperative abdominal distention as ileus, which not only prevents timely
      diagnosis and treatment of early postoperative small bowel obstruction or acute
      colonic pseudo-obstruction but also increases patient morbidity and mortality.

PMID- 22414413
TI  - Perioperative nutritional support: immunonutrition, probiotics, and anabolic
      steroids.
AB  - Nutritional support in surgical patients has evolved from simple provision of
      adequate calories to retard loss of lean body mass to the provision of specific
      nutrients in an attempt to manipulate metabolic and immune responses. Although
      still limited, the current understanding of this complex subject indicates that
      the type, route, amount, and composition of nutritional support provided to
      patients can affect their outcome. Further studies are, however, needed to better
      characterize the exact nutritional support that is most beneficial for a specific
      disease state and a specific patient.

PMID- 22414414
TI  - Surgical prophylaxis and other complication avoidance care bundles.
AB  - Individual health care quality measures that have been shown to improve outcome
      can be combined together into what are called care bundles, with the expectation
      that this set of practices produces further improvements in outcome. Prevention
      of surgical site infection is the focus of several quality measures put forward
      by the Surgical Care Improvement Project; these can collectively be considered a
      bundle as well. Whether these process measures, which include several components
      related to the administration of antibiotic prophylaxis, are effective in
      decreasing rates of surgical site infection has come under considerable debate
      recently.

PMID- 22414415
TI  - Organ failure avoidance and mitigation strategies in surgery.
AB  - Postoperative organ failure is a challenging disease process that is better
      prevented than treated. Providers should use close observation and clinical
      judgment, and checklists of best practices to minimize the risk of organ failure
      in their patients. The treatment of multiorgan dysfunction syndrome (MODS)
      generally remains supportive, outside of rapid initiation of source control (when
      appropriate) and targeted antibiotic therapy. More specific treatments may be
      developed as the complex pathophysiology of MODS is better understood and more
      homogenous patient populations are selected for study.

PMID- 22414416
TI  - Postoperative pulmonary complications: pneumonia and acute respiratory failure.
AB  - Postoperative pulmonary complications (atelectasis, pneumonia, pulmonary edema,
      acute respiratory failure) are common, particularly after abdominal and thoracic
      surgery, pneumonia and atelectasis being the most common. Postoperative pneumonia
      is associated with increased morbidity, length of hospital stay, and costs. Few
      institutions have pneumonia prevention programs for surgical patients, and these
      should be strongly considered. Acute respiratory failure is a life-threatening
      pulmonary complication that requires institution of mechanical ventilation and
      admission to the intensive care unit, and is associated with increased risk for
      ventilator-associated pneumonia. This article discusses epidemiology, risk
      factors, diagnosis, treatment, and prevention of these pulmonary complications in
      surgical patients.

PMID- 22414417
TI  - Multidrug-resistant organisms and antibiotic management.
AB  - The increasing prevalence of multidrug-resistant (MDR) infections in clinical
      practice stems from clinical and veterinary antibiotic use, and animal husbandry.
      As resistance to antibiotics becomes more common, a vicious circle develops
      wherein increasingly broad-spectrum agents must be prescribed empirically to
      ensure that initial antibiotic therapy is adequate to the task, and new, ever
      more powerful agents are needed for the treatment of MDR bacteria. Unfortunately,
      a dearth of new agents and drugs is in development. As clinicians we must learn
      to make do with what we have for the foreseeable future, according to the
      principles of antibiotic stewardship.

PMID- 22414418
TI  - Prevention of chronic pain after surgical nerve injury: amputation and
      thoracotomy.
AB  - Although techniques for acute pain management have improved in recent years, a
      dramatic reduction in the incidence and severity of chronic pain following
      surgery has not occurred. Amputation and thoracotomy, although technically
      different, share the commonalities of unavoidable nerve injury and the frequent
      presence of persistent postsurgical neuropathic pain. The authors review the risk
      factors for the development of chronic pain following these surgeries and the
      current evidence that supports analgesic interventions. The inconclusive results
      from many preemptive analgesic studies may require us to reconceptualize the
      perioperative treatment period as a time of gradual neurologic remodeling.

PMID- 22414419
TI  - Postoperative complications: delirium.
AB  - Delirium is a common feature of the postoperative period, leading to increased
      morbidity and mortality and significant costs. Multiple factors predispose a
      patient to delirium in its hypoactive, hyperactive, or mixed forms. Tools have
      been validated for its quick and accurate identification to ensure timely and
      effective multidisciplinary intervention and treatment. A significant percentage
      of patients may require placement in skilled nursing facilities or similar care
      environments because of the long-lasting effects. The physician must be vigilant
      in the search for and identification of all forms of delirium and must
      effectively treat the underlying medical condition and symptoms.

PMID- 22414420
TI  - Rescue therapies in the surgical patient.
AB  - In the perioperative period, patients may suffer complications leading to serious
      adverse events. Patient deterioration needs to be rapidly identified, and a rapid
      response system must be initiated. Additional personnel may also be needed.
      Rescue therapies, beyond the routine resuscitative efforts, may be needed in some
      cases. The types of complications that may be faced include a difficult airway,
      refractory hypoxemia, pulmonary embolism, myocardial infarction, cardiac arrest
      with restoration of pulse but ongoing coma, and stroke. Although perioperative
      complications can be catastrophic, rapid intervention, including rescue therapies
      when necessary, can improve outcomes.

PMID- 22414421
TI  - The American College of Surgeons Trauma Quality Improvement Program.
AB  - The American College of Surgeons Trauma Quality Improvement Program (ACS TQIP) is
      a recent addition to the many quality improvement collaboratives that have been
      established in surgery. On the background of a well-established trauma center and
      its performance improvement activities, ACS TQIP offers the potential to advance
      trauma care and offers participating centers the opportunity to better understand
      their strengths and areas for improvement. The rationale for ACS TQIP's
      development, implementation challenges, and potential for advancing the quality
      of trauma care are described.

PMID- 22414422
TI  - Management of peri-operative complications.

PMID- 22414423
TI  - Management of peri-operative complications.

PMID- 22414424
TI  - Deep-sea and pelagic rod visual pigments identified in the mysticete whales.
AB  - Our current understanding of the spectral sensitivities of the mysticete whale
      rod-based visual pigments is based on two species, the gray whale (Eschrichtius
      robustus) and the humpback whale (Megaptera novaeangliae) possessing absorbance
      maxima determined from difference spectra to be 492 and 497 nm, respectively.
      These absorbance maxima values are blueshifted relative to those from typical
      terrestrial mammals (~500 nm) but are redshifted when compared to those
      identified in the odontocetes (479-484 nm). Although these mysticete species
      represent two of the four mysticete families, they do not fully represent the
      mysticete whales in terms of foraging strategy and underwater photic environments
      where foraging occurs. In order to better understand the spectral sensitivities
      of the mysticete whale rod visual pigments, we have examined the rod opsin genes
      from 11 mysticete species and their associated amino acid substitutions. Based on
      the amino acids occurring at positions 83, 292, and 299 along with the directly
      determined dark spectra from expressed odontocete and mysticete rod visual
      pigments, we have determined that the majority of mysticete whales possess deep
      sea and pelagic like rod visual pigments with absorbance maxima between 479 and
      484 nm. Finally, we have defined the five amino acid substitution events that
      determine the resulting absorbance spectra and associated absorbance maxima for
      the mysticete whale rod visual pigments examined here.

PMID- 22414425
TI  - Design of cyclic RKKH peptide-conjugated PEG liposomes targeting the integrin
      alpha2beta1 receptor.
AB  - Peptide conjugation to the surface of stealth liposomes has been studied for
      liposomal drug targeting to cells expressing specific receptors to provide a site
      specific drug delivery. This study investigated the potential of peptide
      conjugated liposomes for targeting cells expressing the human integrin
      alpha(2)beta(1) receptor. A 12 amino acid head-to-tail cyclic peptide derived
      from the Jararhagin protein containing the Arg-Lys-Lys-His (RKKH)-specific
      binding site was conjugated to the distal ends of poly(ethylene glycol) (PEG)
      chains on PEGylated liposomes. Epithelial cells expressing the receptor showed
      increased cellular association and uptake of peptide-conjugated liposomes at 4 
      degrees C, compared to liposomes conjugated with a non-specific peptide. The
      interaction between cells and peptide-conjugated liposomes was significantly
      increased at 37  degrees C suggesting that a possible uptake mechanism might be
      energy-dependent endocytosis. In keratinocyte cell cultures, the ligand
      conjugated liposomes loaded with the vitamin D(3) analogue calcipotriol induced
      transcription of the gene encoding the antimicrobial peptide cathelicidin, which
      is activated through the vitamin D(3) receptor upon binding of vitamin D(3)
      analogues. This suggests that the liposomes are internalized and that
      calcipotriol is delivered intracellularly and released in an active form. In
      conclusion, the 12 amino acid head-to-tail cyclic RKKH peptide seems promising
      for targeting of liposomes to the integrin alpha(2)beta(1) receptor.

PMID- 22414426
TI  - Self nanoprecipitating preconcentrate of tamoxifen citrate for enhanced
      bioavailability.
AB  - We disclose a self nanoprecipitating preconcentrate (SNP) of tamoxifen citrate
      (TMX), which forms TMX loaded polymeric nanoparticles, on dilution with aqueous
      media. SNP comprised TMX, polymer (Kollidon SR) and surfactant/s dissolved in a
      pharmaceutically acceptable vehicle. Binary surfactant mixtures of Aerosol OT
      (AOT) with Tween 80 revealed synergistic reduction in surface tension to enable
      both high entrapment efficiency (EE) and low particle size (PS). Synergism of the
      surfactants was confirmed by molecular interaction parameter(beta(sigma)).
      Combination of AOT and Tween 80 resulted in EE (~85%) and PS (<250nm). Formation
      of TMX-KSR nanoparticles in situ was reproducible under most experimental
      conditions and exhibited pH independent behavior. Dilution volume (>80mL)
      influenced both PS and EE while dilution temperature influenced only PS. Marginal
      increase in size was evident at the end of 1h nevertheless was not of concern as
      TMX SNP exhibited near complete release in 1h. DSC and XRD studies revealed
      amorphous nature of TMX in nanoparticles. FTIR imaging confirmed uniform
      distribution of TMX in nanoparticles. ESEM and TEM revealed spherical
      nanoparticles. Biodistribution studies of (99m)Tc labeled TMX SNP in rats
      revealed no significant absorption however oral pharmacokinetics revealed
      enhanced oral bioavailability of TMX (165%) compared to TMX suspension. SNP
      presents a new in situ approach, for design of drug loaded polymeric
      nanoparticles.

PMID- 22414428
TI  - Upholding the highest standards of integrity in the content of the Journal of
      Agricultural and Food Chemistry.

PMID- 22414427
TI  - The evolution of filamin-a protein domain repeat perspective.
AB  - Particularly in higher eukaryotes, some protein domains are found in tandem
      repeats, performing broad functions often related to cellular organization. For
      instance, the eukaryotic protein filamin interacts with many proteins and is
      crucial for the cytoskeleton. The functional properties of long repeat domains
      are governed by the specific properties of each individual domain as well as by
      the repeat copy number. To provide better understanding of the evolutionary and
      functional history of repeating domains, we investigated the mode of evolution of
      the filamin domain in some detail. Among the domains that are common in long
      repeat proteins, sushi and spectrin domains evolve primarily through cassette
      tandem duplications while scavenger and immunoglobulin repeats appear to evolve
      through clustered tandem duplications. Additionally, immunoglobulin and filamin
      repeats exhibit a unique pattern where every other domain shows high sequence
      similarity. This pattern may be the result of tandem duplications, serve to avert
      aggregation between adjacent domains or it is the result of functional
      constraints. In filamin, our studies confirm the presence of interspersed
      integrin binding domains in vertebrates, while invertebrates exhibit more varied
      patterns, including more clustered integrin binding domains. The most notable
      case is leech filamin, which contains a 20 repeat expansion and exhibits unique
      dimerization topology. Clearly, invertebrate filamins are varied and contain
      examples of similar adjacent integrin-binding domains. Given that invertebrate
      integrin shows more similarity to the weaker filamin binder, integrin beta3, it
      is possible that the distance between integrin-binding domains is not as crucial
      for invertebrate filamins as for vertebrates.

PMID- 22414429
TI  - Retraction. Freshly crushed garlic is a superior cardioprotective agent than
      processed garlic.

PMID- 22414430
TI  - Retraction. Does white wine qualify for French paradox? Comparison of the
      cardioprotective effects of red and white wines and their constituents:
      resveratrol, tyrosol, and hydroxytyrosol.

PMID- 22414431
TI  - Retraction. Broccoli: a unique vegetable that protects mammalian hearts through
      the redox cycling of the thioredoxin superfamily.

PMID- 22414432
TI  - On-chip microelectrophoresis for the study of in vitro nonhomologous end-joining
      DNA double-strand break repair.
AB  - Oligomerization of linearized plasmids by nuclear proteins extracts, a recognized
      measure of nonhomologous end-joining (NHEJ) repair capacity, is typically
      assessed through agarose gel electrophoresis, a labor-intensive procedure. In the
      current study, a more convenient NHEJ assay was developed using microchips that
      allow scaled-down separation and quantification. This microchip method allows a
      considerable reduction in sample amount and analysis time with similar costs and
      comparable or slightly better precision. Data obtained with quercetin and
      wortmannin show that the method can be applied to the screening of food
      components and natural products for positive and negative modulators of NHEJ,
      potential chemopreventive and indirect genotoxic compounds, respectively.

PMID- 22414433
TI  - The epigenetic effects of butyrate: potential therapeutic implications for
      clinical practice.
AB  - Butyrate is a short chain fatty acid derived from the microbial fermentation of
      dietary fibers in the colon. In the last decade, multiple beneficial effects of
      butyrate at intestinal and extraintestinal level have been demonstrated. The
      mechanisms of action of butyrate are different and many of these involve an
      epigenetic regulation of gene expression through the inhibition of histone
      deacetylase. There is a growing interest in butyrate because its impact on
      epigenetic mechanisms will lead to more specific and efficacious therapeutic
      strategies for the prevention and treatment of different diseases ranging from
      genetic/metabolic conditions to neurological degenerative disorders. This review
      is focused on recent data regarding the epigenetic effects of butyrate with
      potential clinical implications in human medicine.

PMID- 22414434
TI  - Oxidative stress associated with paternal care in smallmouth bass (Micropterus
      dolomieu).
AB  - In species that provide parental care, care for offspring is often accompanied by
      an increase in locomotor activity and a decrease in feeding opportunities which
      can negatively impact endogenous energy reserves. Depletion of parental energy
      stores and declines in nutritional condition can cause physiological
      disturbances, such as an imbalance between free radical production and available
      antioxidants, known as oxidative stress. Using the teleost smallmouth bass
      (Micropterus dolomieu) as a model, we tested if the energetic challenge
      associated with sole paternal care was associated with oxidative stress. Blood
      samples from parental males were collected throughout parental care, during egg,
      embryo, and larval stages of offspring development, and assayed for both
      antioxidant capacity and oxidative damage. A reduction in oxygen radical
      absorbance capacity was observed during the parental care period, indicating a
      decrease in resistance to oxidative stress. Although no change was observed in
      the reduced:total thiol ratio, a significant increase in the concentration of
      both oxidized and total thiols occurred during the parental care period. No
      increase in the oxidative stress markers 8-hydroxy-2-deoxyguanosine, protein
      carbonyls and lipid peroxides was observed. We concluded that oxidative stress
      did not occur as a result of parental care in the male smallmouth bass. This
      study provides evidence that participation in energetically taxing activities,
      such as parental care, can result in a decrease in antioxidant resources, but may
      not always result in oxidative stress.

PMID- 22414435
TI  - Germination stimulants of Phelipanche ramosa in the rhizosphere of Brassica napus
      are derived from the glucosinolate pathway.
AB  - Phelipanche ramosa is a major parasitic weed of Brassica napus. The first step in
      a host-parasitic plant interaction is stimulation of parasite seed germination by
      compounds released from host roots. However, germination stimulants produced by
      B. napus have not been identified yet. In this study, we characterized the
      germination stimulants that accumulate in B. napus roots and are released into
      the rhizosphere. Eight glucosinolate-breakdown products were identified and
      quantified in B. napus roots by gas chromatography-mass spectrometry. Two (3
      phenylpropanenitrile and 2-phenylethyl isothiocyanate [2-PEITC]) were identified
      in the B. napus rhizosphere. Among glucosinolate-breakdown products, P. ramosa
      germination was strongly and specifically triggered by isothiocyanates,
      indicating that 2-PEITC, in particular, plays a key role in the B. napus-P.
      ramosa interaction. Known strigolactones were not detected by ultraperformance
      liquid chromatography-tandem mass spectrometry, and seed of Phelipanche and
      Orobanche spp. that respond to strigolactones but not to isothiocyanates did not
      germinate in the rhizosphere of B. napus. Furthermore, both wild-type and
      strigolactone biosynthesis mutants of Arabidopsis thaliana Atccd7 and Atccd8
      induced similar levels of P. ramosa seed germination, suggesting that compounds
      other than strigolactone function as germination stimulants for P. ramosa in
      other Brassicaceae spp. Our results open perspectives on the high adaptation
      potential of root-parasitic plants under host-driven selection pressures.

PMID- 22414436
TI  - A novel virus-like double-stranded RNA in an obligate biotroph arbuscular
      mycorrhizal fungus: a hidden player in mycorrhizal symbiosis.
AB  - Arbuscular mycorrhizal (AM) fungi form mutualistic associations with most land
      plants and enhance phosphorus uptake of the host plants. Fungal viruses
      (mycoviruses) that possess a double-stranded RNA (dsRNA) genome often affect
      plant-fungal interactions via altering phenotypic expression of their host fungi.
      The present study demonstrates, for the first time, the presence of dsRNAs, which
      are highly likely to be mycoviruses, in AM fungi. dsRNA was extracted from
      mycelia of Glomus sp. strain RF1, purified, and subjected to electrophoresis. The
      fungus was found to harbor various dsRNA segments that differed in size. Among
      them, a 4.5-kbp segment was termed Glomus sp. strain RF1 virus-like medium dsRNA
      (GRF1V-M) and characterized in detail. The GRF1V-M genome segment was 4,557
      nucleotides in length and encoded RNA-dependent RNA polymerase and a structural
      protein. GRF1V-M was phylogenetically distinct and could not be assigned to known
      genera of mycovirus. The GRF1V-M-free culture line of Glomus sp. strain RF1,
      which was raised by single-spore isolation, produced twofold greater number of
      spores and promoted plant growth more efficiently than the GRF1V-M-positive
      lines. These observations suggest that mycoviruses in AM fungi, at least some of
      them, have evolved under unique selection pressures and are a biologically active
      component in the symbiosis.

PMID- 22414437
TI  - The awr gene family encodes a novel class of Ralstonia solanacearum type III
      effectors displaying virulence and avirulence activities.
AB  - We present here the characterization of a new gene family, awr, found in all
      sequenced Ralstonia solanacearum strains and in other bacterial pathogens. We
      demonstrate that the five paralogues in strain GMI1000 encode type III-secreted
      effectors and that deletion of all awr genes severely impairs its capacity to
      multiply in natural host plants. Complementation studies show that the AWR
      (alanine-tryptophan-arginine tryad) effectors display some functional redundancy,
      although AWR2 is the major contributor to virulence. In contrast, the strain
      devoid of all awr genes (Deltaawr1-5) exhibits enhanced pathogenicity on
      Arabidopsis plants. A gain-of-function approach expressing AWR in Pseudomonas
      syringae pv. tomato DC3000 proves that this is likely due to effector
      recognition, because AWR5 and AWR4 restrict growth of this bacterium in
      Arabidopsis. Transient overexpression of AWR in nonhost tobacco species caused
      macroscopic cell death to varying extents, which, in the case of AWR5, shows
      characteristics of a typical hypersensitive response. Our work demonstrates that
      AWR, which show no similarity to any protein with known function, can specify
      either virulence or avirulence in the interaction of R. solanacearum with its
      plant hosts.

PMID- 22414438
TI  - Inhibition of glutamine synthetase by phosphinothricin leads to transcriptome
      reprograming in root nodules of Medicago truncatula.
AB  - Glutamine synthetase (GS) is a vital enzyme for the assimilation of ammonia into
      amino acids in higher plants. In legumes, GS plays a crucial role in the
      assimilation of the ammonium released by nitrogen-fixing bacteria in root
      nodules, constituting an important metabolic knob controlling the nitrogen (N)
      assimilatory pathways. To identify new regulators of nodule metabolism, we
      profiled the transcriptome of Medicago truncatula nodules impaired in N
      assimilation by specifically inhibiting GS activity using phosphinothricin (PPT).
      Global transcript expression of nodules collected before and after PPT addition
      (4, 8, and 24 h) was assessed using Affymetrix M. truncatula GeneChip arrays.
      Hundreds of genes were regulated at the three time points, illustrating the
      dramatic alterations in cell metabolism that are imposed on the nodules upon GS
      inhibition. The data indicate that GS inhibition triggers a fast plant defense
      response, induces premature nodule senescence, and promotes loss of root nodule
      identity. Consecutive metabolic changes were identified at the three time points
      analyzed. The results point to a fast repression of asparagine synthesis and of
      the glycolytic pathway and to the synthesis of glutamate via reactions
      alternative to the GS/GOGAT cycle. Several genes potentially involved in the
      molecular surveillance for internal organic N availability are identified and a
      number of transporters potentially important for nodule functioning are
      pinpointed. The data provided by this study contributes to the mapping of
      regulatory and metabolic networks involved in root nodule functioning and
      highlight candidate modulators for functional analysis.

PMID- 22414439
TI  - Effector-triggered immunity signaling: from gene-for-gene pathways to protein
      protein interaction networks.
AB  - In its simplicity and testability, Flor's gene-for-gene hypothesis has been a
      powerful driver in plant immunity research for decades. Once the molecular
      underpinnings of gene-for-gene resistance had come into sharper focus, there was
      a reassessment of Flor's hypothesis and a name change to effector-triggered
      immunity. As implied by the name change and exemplified by pioneering studies,
      plant immunity is increasingly described in terms of protein rather than genetic
      interactions. This progress leads to a reinterpretation of old concepts of
      pathogen recognition and resistance signaling and, of course, opens up new
      questions. Here, we provide a brief historical overview of resistance gene
      function and how a new focus on protein interactions can lead to a deeper
      understanding of the logic of plant innate immunity signaling.

PMID- 22414440
TI  - Molecular characterization and functional analysis of a necrosis- and ethylene
      inducing, protein-encoding gene family from Verticillium dahliae.
AB  - Verticillium dahliae Kleb. is a hemibiotrophic, phytopathogenic fungus that
      causes wilt disease in a wide range of crops, including cotton. Successful host
      colonization by hemibiotrophic pathogens requires the induction of plant cell
      death to provide the saprophytic nutrition for the transition from the biotrophic
      to the necrotrophic stage. In this study, we identified a necrosis-inducing
      Phytophthora protein (NPP1) domain-containing protein family containing nine
      genes in a virulent, defoliating isolate of V. dahliae (V592), named the VdNLP
      genes. Functional analysis demonstrated that only two of these VdNLP genes,
      VdNLP1 and VdNLP2, encoded proteins that were capable of inducing necrotic
      lesions and triggering defense responses in Nicotiana benthamiana, Arabidopsis,
      and cotton plants. Both VdNLP1 and VdNLP2 induced the wilting of cotton seedling
      cotyledons. However, gene-deletion mutants targeted by VdNLP1, VdNLP2, or both
      did not affect the pathogenicity of V. dahliae V592 in cotton infection. Similar
      expression and induction patterns were found for seven of the nine VdNLP
      transcripts. Through a comparison of the conserved amino acid residues of VdNLP
      with different necrosis-inducing activities, combined with mutagenesis-based
      analyses, we identified several novel conserved amino acid residues, in addition
      to the known conserved heptapeptide GHRHDWE motif and the cysteine residues of
      the NPP domain-containing protein, that are indispensable for the necrosis
      inducing activity of the VdNLP2 protein.

PMID- 22414441
TI  - The molecular basis of host specialization in bean pathovars of Pseudomonas
      syringae.
AB  - Biotrophic phytopathogens are typically limited to their adapted host range. In
      recent decades, investigations have teased apart the general molecular basis of
      intraspecific variation for innate immunity of plants, typically involving
      receptor proteins that enable perception of pathogen-associated molecular
      patterns or avirulence elicitors from the pathogen as triggers for defense
      induction. However, general consensus concerning evolutionary and molecular
      factors that alter host range across closely related phytopathogen isolates has
      been more elusive. Here, through genome comparisons and genetic manipulations, we
      investigate the underlying mechanisms that structure host range across closely
      related strains of Pseudomonas syringae isolated from different legume hosts.
      Although type III secretion-independent virulence factors are conserved across
      these three strains, we find that the presence of two genes encoding type III
      effectors (hopC1 and hopM1) and the absence of another (avrB2) potentially
      contribute to host range differences between pathovars glycinea and phaseolicola.
      These findings reinforce the idea that a complex genetic basis underlies host
      range evolution in plant pathogens. This complexity is present even in host
      microbe interactions featuring relatively little divergence among both hosts and
      their adapted pathogens.

PMID- 22414442
TI  - Qualitative and quantitative late blight resistance in the potato cultivar Sarpo
      Mira is determined by the perception of five distinct RXLR effectors.
AB  - Potato defends against Phytophthora infestans infection by resistance (R)-gene
      based qualitative resistance as well as a quantitative field resistance. R genes
      are renowned to be rapidly overcome by this oomycete, and potato cultivars with a
      decent and durable resistance to current P. infestans populations are hardly
      available. However, potato cultivar Sarpo Mira has retained resistance in the
      field over several years. We dissected the resistance of 'Sarpo Mira' in a
      segregating population by matching the responses to P. infestans RXLR effectors
      with race-specific resistance to differential strains. The resistance is based on
      the combination of four pyramided qualitative R genes and a quantitative R gene
      that was associated with field resistance. The qualitative R genes include R3a,
      R3b, R4, and the newly identified Rpi-Smira1. The qualitative resistances matched
      responses to avirulence (AVR)3a, AVR3b, AVR4, and AVRSmira1 RXLR effectors and
      were overcome by particular P. infestans strains. The quantitative resistance was
      determined to be conferred by a novel gene, Rpi-Smira2. It was only detected
      under field conditions and was associated with responses to the RXLR effector
      AvrSmira2. We foresee that effector-based resistance breeding will facilitate
      selecting and combining qualitative and quantitative resistances that may lead to
      a more durable resistance to late blight.

PMID- 22414443
TI  - Functional interaction between plastidial starch phosphorylase and starch
      branching enzymes from rice during the synthesis of branched maltodextrins.
AB  - The present study established the way in which plastidial alpha-glucan
      phosphorylase (Pho1) synthesizes maltodextrin (MD) which can be the primer for
      starch biosynthesis in rice endosperm. The synthesis of MD by Pho1 was markedly
      accelerated by branching enzyme (BE) isozymes, although the greatest effect was
      exhibited by the presence of branching isozyme I (BEI) rather than by isozyme IIa
      (BEIIa) or isozyme IIb (BEIIb). The enhancement of the activity of Pho1 by BE was
      not merely due to the supply of a non-reducing ends. At the same time, Pho1
      greatly enhanced the BE activity, possibly by generating a branched carbohydrate
      substrate which is used by BE with a higher affinity. The addition of isoamylase
      to the reaction mixture did not prevent the concerted action of Pho1 and BEI.
      Furthermore, in the product, the branched structure was, at least to some extent,
      maintained. Based on these results we propose that the interaction between Pho1
      and BE is not merely due to chain-elongating and chain-branching reactions, but
      occurs in a physically and catalytically synergistic manner by each activating
      the mutual capacity of the other, presumably forming a physical association of
      Pho1, BEI and branched MDs. This close interaction might play a crucial role in
      the synthesis of branched MDs and the branched MDs can act as a primer for the
      biosynthesis of amylopectin molecules.

PMID- 22414444
TI  - Traumatized and inflamed--but resilient: glial aromatization and the avian brain.
AB  - Steroids like estrogens have potent effects on the vertebrate brain, and are
      provided to neural targets from peripheral and central sources. Estradiol
      synthesized within the vertebrate CNS modulates neural structure and function,
      including the pathways involved in neuroprotection, and perhaps, neural repair.
      Specifically, aromatase; the enzyme responsible for the conversion of
      testosterone to estradiol, is upregulated in the avian and mammalian brain
      following disruption of the neuropil by multiple forms of perturbation including
      mechanical injury, ischemia and excitotoxicity. This injury induced aromatase
      expression is somewhat unique in that it occurs in astroglia rather than neurons,
      and is stimulated in response to factors associated with brain damage. In this
      review, we focus on the induction, expression and consequences of glial
      aromatization in the songbird brain. We begin with a review of the anatomical
      consequences of glial estrogen provision followed by a discussion of the cellular
      mechanisms whereby glial aromatization may affect injury-induced neuroplasticity.
      We then present the current status of our understanding regarding the inductive
      role of inflammatory processes in the transcription and translation of astrocytic
      aromatase. We consider the functional aspects of glial aromatization before
      concluding with unanswered questions and suggestions for future studies. Birds
      have long informed us about fundamental questions in endocrinology, immunology,
      and neuroplasticity; and their unique anatomical and physiological
      characteristics continue to provide an excellent system in which to learn about
      brain trauma, inflammation, and neuroprotection.

PMID- 22414446
TI  - Accessing primary health care: a meta-ethnography of the experiences of British
      South Asian patients with diabetes, coronary heart disease or a mental health
      problem.
AB  - OBJECTIVES: To develop an explanatory framework of the problems accessing primary
      care health services experienced by British South Asian patients with a long-term
      condition or mental health problem. METHODS: This study used meta-ethnographic
      methods. Published qualitative studies were identified from a structured search
      of six databases and themes synthesized across studies to develop a new
      explanatory framework. RESULTS: Initial searches identified 951 potentially
      relevant records from which a total of 27 articles were identified that met
      inclusion and exclusion criteria. Twelve of these articles were chosen on the
      basis of their quality and relevance. These 12 articles described themes relating
      to the cultural, spatial and temporal dimensions of patient experiences of
      accessing and using health care. Our interpretive synthesis showed that access to
      primary care among British South Asians with diabetes, coronary heart disease and
      psychological health problems is co-constructed and negotiated over time and
      space along the key domains of the candidacy model of access: from help-seeking
      to interactions at the interface to following treatment advice. In the case of
      each condition, British South Asians' claims to candidacy were constrained where
      their individual as well as broader social and cultural characteristics lacked
      fit with professionals' ways of working and cultural typifications. CONCLUSION:
      Interventions that positively affect professionals' capacity to support patient
      claims to candidacy are likely to help support British South Asians overcome a
      broad range of barriers to care for physical and mental health problems.

PMID- 22414445
TI  - Racial and ethnic differences in diurnal cortisol rhythms in preadolescents: the
      role of parental psychosocial risk and monitoring.
AB  - Racial/ethnic minorities experience persistent health disparities due in part to
      their exposure to chronic SES and psychosocial risk. The hypothalamic-pituitary
      adrenal axis and its hormonal end product, cortisol, are believed to mediate the
      associations between chronic stress and poor health. In this study, racial/ethnic
      differences in diurnal salivary cortisol rhythms in 179 preadolescent youths and
      the contributing roles of SES risk, psychosocial risk, perceived discrimination,
      harsh parenting, and parental monitoring were examined. The analyses revealed
      racial/ethnic differences in diurnal cortisol rhythms, with African Americans
      having significantly flatter morning-to-evening cortisol slopes than Caucasians
      and with Latinos having significantly lower evening cortisol levels than
      Caucasians. Greater psychosocial risk and less parental monitoring were
      associated with flatter cortisol slopes. Racial/ethnic differences on the
      cortisol measures persisted when controlling for SES, psychosocial risk, and
      parenting quality. The need to assess chronic risk across the lifespan and
      disentangle possible genetic from environmental contributors is discussed.

PMID- 22414447
TI  - Modern or distinct axial bauplan in early hominins? Comments on Haeusler et al.
      (2011).

PMID- 22414449
TI  - Editorial. PSA screening and low risk prostate cancer, what's going on? are we
      shooting the messenger?

PMID- 22414450
TI  - Management of patients with clinical stage I nonseminomatous testicular germ cell
      tumours: active surveillance versus primary chemotherapy versus nerve sparing
      retroperitoneal lymphadenectomy.
AB  - Clinical stage I testicular nonseminomatous germ cell tumours (NSGCT) are highly
      curable. Following orchidectomy a risk-adapted approach using active surveillance
      (AS), nerve sparing  retroperitoneal lymph node  dissection (nsRPLND) and primary
      chemotherapy is recommended by the current guidelines. CS I is defined negative
      or declining tumour markers to their half-life following orchidectomy and
      negative imaging studies of the chest, abdomen and retroperitoneum. Low risk CS I
      NSGCT are defined by the absence of vascular invasion, low percentage of
      embryonal carcinoma (ECA) and low proliferating Ki-67 index. High risk CS I NSGCT
      are defined by the presence of VI, high percentage of ECA and a high Ki-67 index.
      According to the current guidelines, active surveillance, primary chemotherapy
      and nerve sparing RPLND represent 3 treatment options with the same high cure
      rate of about 100% but significantly different long-term  complications.  As
      demonstrated, active surveillance can be performed in low risk and in high risk
      NSGCT with an anticipated relapse rate of about 15% and 50%. The majority of 
      patients will  relapse with good and intermediate prognosis tumours which have to
      be treated with 3 to 4 cycles chemotherapy. About 25% to 30% of these patients
      will have to undergo postchemotherapy RPLND for  residual masses.  Primary
      chemotherapy with 1 -2 cycles PEB is a therapeutic option for high risk clinical
      stage I NSGCT associated with a recurrence rate of only 2-3% and a minimal acute
      and long-term toxicity rate. Nerve sparing RPLND, if performed properly,  will
      cure about 85%  of all high risk patients with clinical stage I NSGCT without the
      need for chemotherapy. Although armchair calculations of the odds of cure and
      toxicity associated with the various treatment options can be performed,
      recommendations about the most optimal  therapy  in clinical stage I NSGCT remain
      controversial. There seems to be a consensus that active surveillance is the
      treatment strategy of choice for CS I low risk patients.  However,  there is no
      clear cut recommendation in high risk patients. Each treatment has its own
      advantages and disadvantages which have to be discussed thoroughly with the 
      patient.  If, however, the positive results of 1 cycle of PEB can be validated,
      it will become the standard cytotoxic approach for clinical stage I NSGCT.

PMID- 22414451
TI  - Transitional cell carcinoma of the upper urinary tract after cystectomy.
AB  - OBJECTIVE: To assess the incidence, characteristics and outcome of upper urinary
      tract tumors (UUTTs) that developed in patients who underwent radical cystectomy
      for  urothelial carcinoma. METHODS: We performed an analysis of original and
      review articles that were related to post-cystectomy UUTTs. The articles were
      published from 1984 through 2011 and  were identified by searching the Pub Med
      database. RESULTS: The incidence of post-cystectomy UUTT ranges from 2-6% and is
      stable over time. The primary risk factors include a tumor in the distal  ureter
      in the cystectomy  specimen and signs of multifocal disease (e.g., multiplicity,
      a history of non-muscle-invasive bladder tumor, diffuse carcinoma in situ and the
      presence of a tumor in the prostatic urethra). The median time between cystectomy
      and UUTT exceeded three years in 70% of the reviewed cases. Even with regular
      radiological follow-up visits, over  50% of  cases were  diagnosed after clinical
      onset, and over 70% were in an advanced stage. Currently, a multidetector
      computed tomography urography is the standard technique  for studying  the upper
      urinary tract. In patients with urinary diversion, the maximum yield of cytology
      can be obtained when this technique is used to confirm a clinical or radiological
      suspicion of UUTT. Nephroureterectomy is the treatment of choice for these
      tumors. The high prevalence of high-grade and stage UUTT results in
      endourological treatment being  restricted to only selected cases. Despite
      surgery, fewer than 30% of post-cystectomy UUTT patients experience prolonged
      survival. CONCLUSIONS: Post-cystectomy UUTT is rare and usually has a late onset.
      A distal ureteral tumor and the presence of multifocal disease are its primary
      risk factors.  Most cases of post-cystectomy UUTT are diagnosed clinically and in
      advanced stages.

PMID- 22414452
TI  - Neuroendocrine carcinoma of the urinary bladder. 15-year retrospective analysis.
AB  - OBJECTIVES: Neuroendocrine tumors (NET) are cancers found in the bronchopulmonary
      tract, where they were first described in 1926. The tumors are associated  with
      poor  prognosis due to their high metastatic potency even after radical
      treatments associated with other neo- or adjuvant therapies. NET of the urinary
      bladder is a rare tumor and accounts for 0.5% of bladder tumors. METHODS: The
      study was designed as an observational, descriptive and retrospective study of 13
      patients diagnosed, treated, and followed for NET of the urinary bladder  at the
      Hospital and University Complex of Albacete, Albacete, Spain between 1995 and
      2010. RESULTS: The sample was composed of 11 men and 2 women. Mean patient age at
      the time of diagnosis was 71 (range, 57-88; SD, 6.98) years. T4 (6  patients) was
      the most  common T tumor stage, followed by T2 (5 patients) and T3 (2 patients).
      In the case of N tumor stage, the most common was N2. In the remaining 3 
      patients, the degree of  lymph node involvement could not be assessed. Six
      presented distant metastasis at the time of diagnosis. Eleven patients presented
      small-cell NET on histology. Seven  underwent radical surgery (radical
      cystectomy). All other patients were treated by deep transurethral resection of
      bladder tumor, except for 1 patient treated  by partial  cystectomy. Adjuvant
      chemo-therapy (usually an association of carboplatin/cisplatin and etoposide) was
      administered to 4 patients. Of these 4  patients, 2 were also treated  by pelvic
      radiotherapy. Two patients survived more than 5 years following diagnosis. In
      fact, at the time the study data was collected only 4 patients had survived and 2
      presented tumor recurrence. Of the 9 deaths, 8 occurred within 6 months of
      diagnosis and 1 at 24 months. All of them were the result of the disease itself.
      CONCLUSIONS: Neuroendocrine tumor of the urinary bladder is a rare, aggressive
      tumor with high metastatic potential that should be considered in the
      differential diagnosis  of urinary bladder neoplasms. Despite various
      multimodality treatments have been used prognosis is poor.

PMID- 22414453
TI  - Outcomes and complications of sphincterotomy with bladder neck incision in
      neurologically healthy male patients with voiding dysfunction.
AB  - OBJECTIVES: To evaluate the efficacy, complications and outcomes of
      sphincterotomy with bladder neck incision in patients with voiding dysfunction
      (VD). METHODS: We evaluated our prospectively established urologic urodynamic
      database and identified the records of 30 male patients with VD that underwent 
      sphincterotomy between Octuber 1993 and December 2008. The IPSS and urodynamics
      were analyzed before and after surgery, we recorded the outcomes and
      complications.  Numerical data were analyzed with Student's t and Wilcoxon tests
      (p < 0.05). ANOVA was used for the follow up. RESULTS: Thirty patients underwent
      sphincterotomy with a mean age of 41 years (range 18-63 years). Statistical
      differences  (p< 0.05) were found for: maximum  flow rate (17.61 +/- 7.7 vs 23.5
      +/- 12.19 ml/s), detrusor pressure (73.53 +/- 21.51 vs 47.4 +/- 16.24 cmH20),
      maximum  cystometric capacity (462.74 +/- 224.2 vs 382.2 +/- 167.48 ml), 
      functional urethral length (64.3 +/- 22.6 vs 42.2 +/- 18.4 mm), Maximum urethral
      pressure (120.1 +/- 46.8 vs 59.23+/- 22.67  cmH20), total  urethral closure area
      (3315 +/- 1269.7 vs  1189 +/- 49.23 cmH20*mm) and postvoid residual volume (161.3
      +/- 177.9 vs 57 +/- 100.8 ml). The IPSS improved and was stable at 60  months (p
      < 0.02).  No significant association  was found to develop incontinence after the
      procedure. CONCLUSION: Sphincterotomy for male patients with dysfunctional
      voiding improves voiding dynamics with a low rate of complications and minimum
      risk of incontinency.

PMID- 22414454
TI  - Double J catheter migrated to the bladder and encrusted. Case report and
      bibliographic review.
AB  - OBJECTIVE: Urinary tract obstruction is one of the most prevalent diseases in
      urology. The handling of it includes conservative (analgesia and fluid therapy)
      and  invasive (urinary diversion) measures. Ureteral stent is the method
      currently employed for urinary tract diversion. Complications of urinary tract
      stents maintenance  have already been studied and are well known. We report a
      case of ureteral stent migrated to the bladder, calcified and embedded and we
      review the existing literature. METHODS: A 28 year-old man with the diagnosis of
      ureteral stent coiled in bladder and calcified. The patient was successfully
      operated of suprapubic cystolithotomy. We conducted a Medline search using the
      terms "ureteral stent "+" embedded stent, "" bladder ureteral stent, "incrusted
      bladder stent" and "ureteral stent complicactions". RESULTS: He is currently free
      of disease. We found a total of 45 articles that responded to the search
      criteria, from which we select the highest citation index. CONCLUSIONS: The use
      of ureteral stents for urinary diversion of the upper urinary tract is safe and
      well tolerated but not without complications, that is why we  have to raise
      awareness among patients of the need to undergo periodic inspections and instruct
      them to possible symptoms and / or signs that may indicate changes  in position
      and / or state of the stent.

PMID- 22414455
TI  - Xenograft iterposition in female urethral diverticulum surgery.
AB  - OBJECTIVE: To describe the use collagen xenograft as adjuvant therapy in the
      surgical treatment of female urethral diverticulum (FUD) and  to perform a
      bibliographic review. METHODS: We performed a surgical approach to remove the
      diverticulum and repair the remaining dead space with a porcine collagen mesh to
      avoid fistulas. Monitoring  is done by MRI. RESULTS: After two years of follow up
      the patient improved considerably, disappearing the previous symptoms. Follow-up
      MRI showed no abnormality: There  was no inflammatory reaction or encapsulation
      of any kind. CONCLUSIONS: We recognize that the flap or the use of a xenograft
      are not always necessary, but due to its technical simplicity and effectiveness,
      it is an important  tool for diverticulum surgery. However, more experience is
      needed to assess the appropriateness of this method.

PMID- 22414456
TI  - Antopol-Goldman lesion: a rare clinical entity in the differential diagnosis of
      macroscopic hematuria.
AB  - OBJECTIVE: To describe the case of a patient with gross hematuria. The
      pathological study revealed a subepithelial hematoma of the renal pelvis (Antopol
      Goldman  lesion). METHODS/RESULTS: An 86 year-old woman presented with gross
      hematuria through the right ureteral orifice. A filling defect is visualized in
      the right renal  pelvis on CT and right nephroureterectomy was carried out after
      the diagnosis of suspicious upper urinary tract tumor. The pathological study
      revealed the presence of a subepithelial  hematoma without evidence of
      malignancy. CONCLUSION: Antopol-Goldman lesion is a benign condition that one
      must have in mind in the work up of patients with hematuria and filling defects
      in the urinary  tract who present a predisposing factor for pyelic hematoma.

PMID- 22414457
TI  - Ultrasound diagnosis of three cases of Mondor's disease.
AB  - OBJECTIVE: To describe clinical features and ultrasound findings of three cases
      of a little-known and relatively infrequent entity in daily clinical activity,
      which  is often unnoticed and under-reported: penile Mondor's disease or
      superficial penile veins thrombophlebitis. METHODS: We are reporting the cases of
      three patients aged 33, 25 and 39 years who were referred to our department, the
      first case with suspicion of inguinal hernia,  the second one to rule out
      testicular pathology because of pubic and perineal discomfort, and the third one
      for painful induration of the dorsal region of the penis. The three patients
      underwent Doppler-ultrasound examination (Toshiba(r), using a 13-18MHz linear 
      transducer)  to establish definitive diagnosis, and had a favorable evolution
      with conservative management. RESULTS: Ultrasound examination revealed: Case 1.
      Penile superficial dorsal vein and lateral superficial veins thrombosis. Case 2.
      Thrombosis of the right branch of  the superficial dorsal vein and its perineal
      distal connections. Case 3. Penile superficial dorsal vein thrombosis. Definitive
      diagnosis of the three cases was Mondor's disease. CONCLUSIONS: Mondor's disease
      is an often under-reported entity in daily clinical activity. Doppler-ultrasound
      findings  (echogenic material within veins, lack of any response after
      compression by the transducer and absence of color flow) confirm de diagnosis.
      This disease has  a favorable evolution and functional prognosis. Knowledge of
      Mondor's disease by echographists is basic to avoid false-negative results in
      radiologic examination.

PMID- 22414458
TI  - Subcutaneous urinary extravasation after percoutaneous nephrolithotomy.

PMID- 22414459
TI  - Intravesical thermometer.

PMID- 22414460
TI  - Individualized guidelines for the management of aggression in dementia - Part 1:
      key concepts.
AB  - BACKGROUND: Clinical guidelines have the potential to assist in the management of
      aggression in dementia. This study aims to develop a conceptual framework for the
      construction of individualized guidelines for this group. METHODS: A concept map
      of the topic "How to manage aggression in dementia" was developed by reviewing
      research papers, clinical guidelines, and gray literature. Titles and abstracts
      of papers that met search criteria were manually scanned in an iterative process
      for the extraction of key ideas and terminology commonly used to describe the
      field. Essential ideas and concepts were recorded on a concept map and
      hierarchically arranged. The concept map was converted into an interactive PDF
      document for easy distribution and sharing. RESULTS: Ten key concepts were found
      to be important when managing aggression in dementia clustered along three major
      dimensions: Patient, Disorder and Treatment. The dimension Patient was defined by
      the "Patient's individual characteristics," the "Personal life story," and the
      "Patient's environment." Disorder was defined by the "Presentation of symptoms"
      and "Theory of causation." Treatment was defined by "Goals and expectations,"
      "Non-pharmacological interventions," "Pharmacological interventions," "Ethics and
      Restraint Use," and "Emergency treatment." Concepts relating to clinical
      guidelines themselves were also included in the interactive map, including
      "Support from evidence-based medicine," "Regular updates," "Disclosures," and
      "Usability." CONCLUSION: Managing aggression in dementia requires consideration
      of a wide range of factors relating to the patient, the dementia and behavioral
      disturbance, and possible treatment options. An interactive and hierarchical
      concept map provides a framework to develop individualized clinical guidelines.

PMID- 22414461
TI  - Virtual reality simulator training of laparoscopic cholecystectomies - a
      systematic review.
AB  - BACKGROUND AND AIMS: Simulators are widely used in occupations where practice in
      authentic environments would involve high human or economic risks. Surgical
      procedures can be simulated by increasingly complex and expensive techniques.
      This review gives an update on computer-based virtual reality (VR) simulators in
      training for laparoscopic cholecystectomies. MATERIALS AND METHODS: From leading
      databases (Medline, Cochrane, Embase), randomised or controlled trials and the
      latest systematic reviews were systematically searched and reviewed. Twelve
      randomised trials involving simulators were identified and analysed, as well as
      four controlled studies. Furthermore, seven studies comparing black boxes and
      simulators were included. RESULTS: The results indicated any kind of simulator
      training (black box, VR) to be beneficial at novice level. After VR training,
      novice surgeons seemed to be able to perform their first live cholecystectomies
      with fewer errors, and in one trial the positive effect remained during the first
      ten cholecystectomies. No clinical follow-up data were found. Optimal learning
      requires skills training to be conducted as part of a systematic training
      program. No data on the cost-benefit of simulators were found, the price of a VR
      simulator begins at EUR 60 000. CONCLUSIONS: Theoretical background to learning
      and limited research data support the use of simulators in the early phases of
      surgical training. The cost of buying and using simulators is justified if the
      risk of injuries and complications to patients can be reduced. Developing
      surgical skills requires repeated training. In order to achieve optimal learning
      a validated training program is needed.

PMID- 22414462
TI  - Fifty-four emergent cricothyroidotomies: are surgeons reluctant teachers?
AB  - BACKGROUND: Emergent cricothyroidotomy remains an uncommon, but life-saving, core
      procedural training requirement for emergency medicine (EM) physician training.
      We hypothesized that, although most cricothyroidotomies occur in the emergency
      department (ED), they are rarely performed by EM physicians. METHODS: We
      conducted a retrospective analysis of all emergent cricothyroidotomies performed
      at two large level one trauma centers over 10 years. Operators and assistants for
      all procedures were identified, as well as mechanism of injury and patient
      demographics were examined. RESULTS: Fifty-four cricothyroidotomies were
      performed. Patients were: mean age of 50, 80% male and 90% blunt trauma. The most
      common primary operator was a surgeon (n = 47, 87%), followed by an Emergency
      Medical Services (EMS) provider (n = 6, 11%) and a EM physician (n = 1, 2%). In
      all cases, except those performed by EMS, the operator or assistant was an
      attending surgeon. All EMS procedures resulted in serious complications compared
      to in-hospital procedures (p < 0.0001). CONCLUSIONS: 1. Pre-hospital
      cricothyroidotomy results in serious complications. 2. Despite the ubiquitous
      presence of emergency medicine physicians in the ED, all crico-thyroidotomies
      were performed by a surgeon, which may represent a serious emergency medicine
      training deficiency.

PMID- 22414463
TI  - Single-incision laparoscopic colectomy using the Gelport system for early colon
      cancer.
AB  - BACKGROUND: Laparoscopic surgery has spread quickly during the past twenty years,
      and has become one of the important treatments in the field of colorectal
      surgery. Recently, natural orifice transluminal endoscopic surgery (NOTES) has
      been studied as the next generation of minimally-invasive surgery, but the
      feasibility and safety of the NOTES method have not been evaluated. In such a
      situation, single-incision laparoscopic surgery has attracted interest from
      surgeons worldwide. However, single-incision laparoscopic colorectal surgery has
      not yet been standardized. METHODS: From February 2010, single-incision
      laparoscopic colectomy was performed for 7 patients presenting with early colon
      cancer. All procedures were performed by two experts with the License of
      Endoscopic Surgical Skill Qualification System (ESSQS) of Japan Society for
      Endoscopic Surgery (JSES) in the field of colorectal Surgery. RESULTS: We used
      the Gelport system (Applied Medical, Rancho Santa Margarita, CA, USA) as the
      access port and 3 trocars of different sizes (Ethicon, Inc., Cincinnati, OH,
      USA). Using this technique, we did not experience any difficulties or use any
      articulated instruments. All of the present 7 patients underwent the single
      incision laparoscopic colectomy successfully and had no complications.
      CONCLUSION: Single-incision laparoscopic surgery using the Gelport was performed
      safely in the present cases. The use of the Gelport as an access port can address
      the technical difficulty associated with this new technique.

PMID- 22414464
TI  - Proximal bowel necrosis after high ligation of the inferior mesenteric artery in
      colorectal surgery.
AB  - BACKGROUND AND AIMS: High ligation of the inferior mesenteric artery may
      jeopardize blood supply to the proximal bowel. We undertook this study to review
      the clinical features and outcomes of patients who developed proximal bowel
      necrosis after high ligation of the inferior mesenteric artery, and to assess the
      incidence and the risk factors for this complication. MATERIALS AND METHODS: A
      retrospective analysis of patients undergoing high or low ligation for sigmoid
      colon and rectal cancer with a primary anastomosis between April 2004 and March
      2009 was performed. Patient and tumor characteristics and the incidence of bowel
      necrosis were reviewed. RESULTS: Four hundred and nine patients were included to
      the analysis. Six out of 302 patients (2.0%) with high ligation developed
      proximal bowel necrosis, while the remaining 107 patients with low ligation did
      not suffer from this complication. All patients who developed proximal bowel
      necrosis underwent secondary surgery with resection of necrotic bowel. The
      pathological examination of the resected specimen revealed mucosal to transmural
      ischemic necrosis without the evidence of vascular thrombosis or embolic
      occlusion. Univariate analysis revealed that advanced age, cerebrovascular
      disease, and hypertension were significantly associated with proximal bowel
      necrosis. Multivariate analysis demonstrated that cerebrovascular disease was an
      independent predictor of this complication. Of these six patients, two died from
      associated complications. CONCLUSIONS: Proximal bowel necrosis after high
      ligation is potentially fatal, and this report provides a warning in clinical
      settings where high ligation is indicated. Further studies are warranted to
      evaluate its distinct relationship with high ligation and to clarify whether low
      ligation would be a safeguard.

PMID- 22414465
TI  - Survival after adjuvant chemoradiotherapy or surgery alone in resectable
      adenocarcinoma at the gastro-esophageal junction.
AB  - BACKGROUND AND AIMS: Longterm survival after curative resection for
      adenocarcinoma at the gastro-esophageal junction (GEJ) range between 18% and 50%.
      In the pivotal Intergroup-0116 Phase III trial by Macdonald et all, adjuvant
      chemoradiotherapy improved both disease-free and overall survival in curatively
      resected patients with mainly gastric adenocarcinoma. We compared survival data
      for curatively resected patients with adeno-carcinoma solely at the gastro
      esophageal junction (GEJ), treated with surgery alone or surgery and adjuvant
      chemoradio-therapy. METHODS: From 2003 to 2009, 211 patients underwent curative
      resection. Surgery alone was performed in 95 pa-tients and 116 patients received
      adjuvant therapy after resection. All patients underwent Lewis-Tanner operation
      with D1 node resection including coliac nodes (D1+). Informations about
      recurrence and death were collected from the Danish Cancer Register and the
      Central Death Register. Patients who died after experiencing severe complications
      after surgery were excluded from the survival analysis. Patients with T0N0 or
      T1N0 were also excluded because patients of this category were not given adjuvant
      therapy according to the Macdonald protocol. RESULTS: Patients with positive node
      status in the resected specimen, the 3-year disease-free survival after adjuvant
      chemoradiotherapy (n = 91) or surgery alone (n = 43) was 24% and 37%,
      respectively. Median time of survival was prolonged by 10 month in favour of
      those who received chemoradiotherapy. However, after controlling for the
      confounding effect of age and node status, only positive node status in the
      resected specimen had significant partial effect on survival. CONCLUSION:
      Chemoradiotherapy according to the Intergroup-0116 protocol might still be a
      reasonable option after curative resection in patients with GEJ adenocarcinomas
      and positive lymph node status, who did not receive neoadjuvant chemotherapy.

PMID- 22414466
TI  - The introduction of a laparoscopic liver surgery programme: a cost analysis of
      initial experience in a university hospital.
AB  - BACKGROUND AND AIMS: In the era of expanding costs of healthcare, this study was
      conducted to perform a cost analysis of introducing a laparoscopic liver surgery
      programme for left sided liver lesions. MATERIALS AND METHODS: Consecutive
      patients treated by laparoscopic liver resections of left lateral segments were
      included. Controls were a group of 14 patients undergoing open resection for
      similar pathology. Primary outcomes were costs. Secondary outcomes were
      complications, conversions, blood loss, length of operation, and length of
      hospital stay. RESULTS: The laparoscopic approach for hepatic left lateral
      resection (bisegmentectomy 2 and 3) was performed in fourteen patients (group I,
      median age 54 [range 26-82] years). In the open group, fourteen patients from a
      prospectively collected database with the same type of resection were selected
      (group II, median age 64 [range 29-76] years). Costs of theatre usage in the
      laparoscopic group were significantly lower (p=0.031). No significant differences
      in costs of disposable instruments, ward stay and total costs were observed
      between the two groups. There were three complications in the laparoscopic group
      compared with two complications in the open group. In the laparoscopic group
      there were 2 conversions (14%). Median blood loss was significantly lower in the
      laparoscopic group (50 mls [range 0-750], (p=0.001) versus the open group (500
      mls [range 150-750]). Furthermore, operation time was also significantly lower in
      the laparoscopic group (116 [range 85-261] minutes) versus the open group (165
      [range 96-217] minutes, p=0.016). Median length of stay was 6 [range 4-11] days
      in group I versus 6 [range 5-13] days in group II (p=0.508). CONCLUSION: Costs of
      laparoscopic liver resections proved to be equivalent to open surgery.
      Furthermore, implementation of a laparoscopic liver resection programme seems
      feasible and safe with reduced blood loss and operation time and comparable
      morbidity and length of stay.

PMID- 22414467
TI  - Preliminary study analyzing the methylated genes in the plasma of patients with
      pancreatic cancer.
AB  - BACKGROUND AND AIMS: CpG islands of the promoter region of some genes are
      methylated in pancreatic cancer tissue and the detection of this methylation has
      been suggested to be useful in the diagnosis of various cancers. The aim of this
      study was to investigate whether the detection of methylated CpG islands in
      plasma can be used in the diagnosis of pancreatic cancer. MATERIAL AND METHODS:
      Plasma DNA was collected from patients with pancreatic cancer, chronic
      pancreatitis, and healthy controls. The methylation status of six genes, UCHL1,
      NPTX2, SARP2, ppENK, p16, and RASSF1A, was checked by methylation-specific PCR
      and was subsequently confirmed by direct sequencing after bisulfite treatment.
      RESULTS: CpG island methylation was detectable in 13 of 16 patients (81.3%) with
      pancreatic cancer, 1 of 29 healthy controls (3.5%), and 8 of 13 patients with
      chronic pancreatitis (61.5%). The mean number of genes with CpG island
      methylation was 1.6+/-1.2 in pancreatic cancer, 0.04+/-0.19 in healthy controls,
      and 1.2+/-1.1 in chronic pancreatitis. Among six genes, p16 was more specifically
      methylated in pancreatic cancer compared with chronic pancreatitis (p=0.016). The
      methylation status was not correlated with smoking history, tumor size, or cancer
      stage. CONCLUSIONS: The detection of methylated genes in the plasma may have a
      role in differentiating between pancreatic cancers and healthy controls but not
      between pancreatic cancer and chronic pancreatitis.

PMID- 22414468
TI  - ERCP procedures in a Finnish community hospital: a retrospective analysis of 1207
      cases.
AB  - BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is a
      procedure with a risk of serious and life-threatening complications. The most
      common complications are pancreatitis, haemorrhage, perforation and cholangitis.
      The aim of this study was to determine indications, success rates and
      complications in a low-volume ERCP unit in Kanta-Hame Central Hospital (KHCH).
      MATERIAL AND METHODS: Data on 1207 consecutive ERCPs performed in KHCH between
      2002 and 2009 was collected retrospectively from patient histories. Complications
      were classified according to need for intervention and length of hospitalisation.
      RESULTS: Cannulation of the desired duct was successful in 89.2% of 825 ERCPs
      with no earlier sphincterotomy. Complete stone removal was achieved in 91.3% of
      procedures. Standard biliary sphincterotomy was performed in 73.8% and precut
      sphincterotomy in 12.0 % of cases. Cholangitis developed in 2.1%, bleeding in
      1.9%, pancreatitis in 1.9%, perforation in 1.0% and cardio-pulmonary or
      miscellaneous complications in 4.2% of cases. The majority of complications could
      be managed conservatively. In procedures with no earlier sphincterotomy ERCP
      related 30-day mortality was 0.2% (n=2) and overall 30-day mortality was 3.3%
      (n=27). CONCLUSIONS: ERCP indications and success rates, as well as morbidity and
      mortality were comparable to those re-ported earlier. Although the success rate
      of cannulation and thereby ERCP procedures seem to be somewhat lower than in
      tertiary referral centres, ERCP procedures can be safely performed in a low
      volume ERCP unit by concentrating procedures on a few experienced endoscopists.
      The success rates may be further improved with the latest cannulation techniques,
      used selectively in the last years of the study period.

PMID- 22414469
TI  - Characteristics and differences in necrotizing fasciitis and gas forming
      myonecrosis: a series of 36 patients.
AB  - BACKGROUND AND AIMS: Necrotizing fasciitis (NF) and gas forming myonecrosis
      (GFM), both being subtypes of necrotizing soft tissue infection (NSTI), are life
      threatening conditions sharing certain similarities. Despite the necessity of
      early and radical surgical debridement in necrotizing infections, the distinction
      between these entities is of clinical relevance since gas forming myonecrosis in
      a number of cases results from an underlying abdominal cause and the focus of
      infection can be missed. This study was to evaluate the incidence and risk
      factors as well as the mortality rate in patients with NSTI and GFM. MATERIAL AND
      METHODS: All patients with NSTI treated in the authors' hospital between January
      2005 and Decem-ber 2009 were enrolled in the study. Medical records, histological
      slides, microbiological and laboratory parameters as well as Computerized
      Tomography (CT) and magnetic resonance imaging (MRI) scans were reviewed for all
      patients. Differences between NF and GFM regarding hospital stay, number of
      surgical interventions and pre-existing comorbidities as well as mortality rate
      were analyzed. The laboratory risk factor for necrotizing fasciitis (LRINEC)
      score was calculated in all patients on admission. RESULTS AND CONCLUSIONS:
      Thirty patients (17 female, 13 male) with necrotizing fasciitis with a mean age
      of 55 years (SD 15.5) were included in the study. There was no statistically
      significant difference between survivors and deceased patients comparing the
      LRINEC score (n.s.). Patients with necrotizing fasciitis secondarily involving
      the trunk had a significantly higher mortality rate (OR 11.2; 95% CI=1.7-72.3).
      In the majority of cases (12 cases), minor skin lesions were identified as the
      site of origin. Amongst all necrotizing soft tissue infections six patients
      (female n=3; male n=3) with a mean age of 61.5 years (SD 12.2) with non
      clostridial gas forming myonecrosis were identified. Three patients had a history
      of malignancy and in three patients the infection was secondary to major surgery.
      The mean LRINEC score was 8.5 (SD 1). Three patients (50%) died due to GFM. Early
      diagnosis and appropriate intervention is critical to provide accurate treatment
      decisions. Eradicating the differing primary sources of infection in GFM and NF
      will have a positive impact on outcome.

PMID- 22414470
TI  - Sensitivity of MRI for articular cartilage lesions of the patellae.
AB  - BACKGROUND AND AIMS: Reliable diagnosis of articular cartilage lesions of the
      patellae is often based on arthroscopy. However, unnecessary arthroscopies should
      be avoided. The aim of this study was to assess the sensitivity and applicability
      of MRI to diagnosing articular cartilage lesions of the patellae. MATERIALS AND
      METHODS: We identified 74 consecutive males (mean age 21 years, range 18-28) from
      the medical records of our institute with the sole diagnosis of articular
      cartilage lesions of the patellae based on arthroscopy. Magnetic resonance
      imaging was performed with 1.0 Tesla scanner a mean of 4 weeks before
      arthroscopy. Sensitivity of symptoms, and MRI for the diagnosis was calculated.
      RESULTS: Based on arthroscopy, 20 (27%) cases of cartilage lesions of the
      patellae were grade-I, 32 (43%) were grade-II, and 22 (30%) were grade-III. MRI
      revealed cartilage lesions of the patellae in 49 knees (66%), indicating that the
      sensitivity of MRI was 66% (95% CI: 53%-74%). MRI sensitivity increased with the
      severity of chondral lesions: all grade III to IV lesions were detected
      (sensitivity 100%, 95% CI: 85%-100%) by MRI. Grade of articular cartilage lesions
      of the patellae based on arthroscopy was not associated with clinical symptoms
      (p=0.61). CONCLUSIONS: The sensitivity of 1.0 Tesla MRI for detecting grade-I
      lesions was low and could not be used to confirm the diagnosis of articular
      cartilage lesions of the patellae. For the detection of more severe grade-II to
      III lesions, the MRI sensitivity was markedly higher. MRI may thus be considered
      an accurate diagnostic tool for identifying more severe cases of articular
      cartilage lesions of the patellae.

PMID- 22414471
TI  - Early results of large head metal-on-metal hip arthroplasties.
AB  - BACKGROUND AND AIMS: Total hip arthroplasty significantly improves patient's life
      quality. However, total joint replacement is associated with possible
      complications, such as dislocations, infections, fractures and periprosthetic
      osteolysis. The goal of this study was to evaluate a large head metal-on-metal
      total hip arthroplasties and analyse short term complications related to them.
      MATERIAL AND METHODS: Between 9/2005 and 6/2009, a total of 691 hip replacements
      were performed on 635 patients with the use of Magnum M2 large head cementless
      metal-on-metal prosthesis in Turku University Hospital. All patients had a
      scheduled follow-up at two to three months, and at one year. The results were
      evaluated using X-rays, Harris Hip Score (HHS), and evaluating post-operative
      complications and reasons for re-operations. RESULTS: During our follow-up the
      HHS median raised from its preoperative value of 59.8 to 86.4 two to three months
      after the operation, and to 93.9 one year after the operation. As a complication
      we had five infections requiring single open debridement (early infection) or a
      two stage revision. Seven patients had a periprosthetic femoral fracture that was
      operated and 11 patients were reoperated because of acetabular component
      malposition, fracture or early loosening. We did not observe any dislocations, n.
      ischiadicus damages, squeeking or complications related to high metal ion release
      (ALVAL-reactions (Aseptic Lymphocyte-dominated Vasculitis-Associated Lesion) or
      pseudotumours). CONCLUSIONS: The metal-on-metal bearing pair allows large femoral
      head size, which decreases the risk for dislocation. It may also decrease the
      risk for osteolysis and aseptic loosening in a long run. Early complication rate
      related to the bearing surface is minimal. Metal-on-metal prosthesis is a good
      choice for young and active patients with good bone quality.

PMID- 22414472
TI  - Posterolateral spondylodesis using bioactive glass S53P4 and autogenous bone in
      instrumented unstable lumbar spine burst fractures. A prospective 10-year follow
      up study.
AB  - BACKGROUND AND AIMS: A prospective long-term follow-up study of bioactive glass
      (BAG)-S53P4 and autogenous bone (AB) used as bone graft substitutes for
      posterolateral spondylodesis in treatment of unstable lumbar spine burst
      fractures during 1996-1998 was conducted. MATERIAL AND METHODS: The lumbar
      fractures were fixed using posterior USS instrumentation. BAG was implanted on
      the left side of the fusion-bed and AB on the right side. The operative outcome
      was evaluated on X-rays and CT scans, and a clinical examination was also
      performed. RESULTS: The Oswestry score was excellent, and the mean pain score 1.
      The mean compression rate of the injured vertebral body was 25%. A solid bony
      fusion was seen on CT scans on the AB side in all patients and on the BAG side in
      five patients, and a partial fusion in five patients, resulting in a total fusion
      rate of 71% of all fused segments in the BAG group. CONCLUSIONS: Our long-term
      results show that BAG-S54P4 bone graft material is safe to be used as a bone
      graft extender in spine surgery.

PMID- 22414473
TI  - Ethanol extract from a Chinese herbal formula, "Zuojin Pill", inhibit the
      expression of inflammatory mediators in lipopolysaccharide-stimulated RAW 264.7
      mouse macrophages.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Zuojin Pill (ZJP), a traditional Chinese
      medicinal decoction that has been used in treating gastritis, gastric ulcer since
      15th century, contains two herbs: Rhizoma Coptidis and Fructus Evodiae in the
      ratio of 6:1 (w/w). Alkaloids are the main active principles contributing to
      ZJP's efficacy, but anti-inflammatory mechanism has not been fully clarified. AIM
      OF THE STUDY: The objective of the study is to reveal anti-inflammatory molecular
      mechanism of ethanol extract from ZJP, which would form an additional proof to
      the traditional experience of ZJP in clinical administration. MATERIALS AND
      METHODS: Seven alkaloids were determined from the ethanol extract of ZJP using
      high performance liquid chromatography (HPLC) with the gradient mobile phase. The
      ethanol extract from ZJP were used to evaluate the anti-inflammatory action in
      murine macrophage cell line RAW 264.7 treated with lipopolysaccharide (LPS).
      Production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) were measured by
      the Griess colorimetric method and enzyme-linked immunosorbent assay (ELISA),
      respectively. Proteome profiler array was analyzed to evaluate 40 cytokines at
      protein level. In addition, interleukin 6 (IL-6) and tumor necrosis factor-alpha
      (TNF-alpha) synthesis were analyzed using ELISA to confirm the result of the
      Proteome profiler array. The gene expression levels of inducible nitric oxide
      synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-alpha, IL-6, and interleukin 1beta
      (IL-1beta) were detected by quantitative real-time reverse-transcription
      polymerase chain reaction (real-time RT-PCR). Furthermore, the nuclear
      translocation of the NF-kappaB p50 and p65 subunits was detected with ELISA.
      RESULTS: The secretions of NO, PGE(2) and the mRNA expression of iNOS, COX-2 were
      significantly inhibited, moreover, the protein and mRNA expressions of IL-6, IL
      1beta and TNF-alpha were inhibited by preventing the nuclear translocation of the
      NF-kappaB p50 and p65 subunits. The proteome profiler array showed that 15
      cytokines and chemokines involved in the inflammatory process were down-regulated
      by ZJP. CONCLUSION: These results suggest that the anti-inflammatory properties
      of ethanol extract from ZJP might be the results from the inhibition of iNOS, COX
      2, IL-6, IL-1beta, and TNF-alpha expression through preventing the nuclear
      translocation of the NF-kappaB p50 and p65 subunits in RAW 264.7 cells. In
      addition, these results provided evidence to understand the therapeutic effects
      of ZJP on gastritis, gastric ulcer, and other inflammatory diseases in clinic.

PMID- 22414474
TI  - Danggui-Shaoyao-San ameliorates cognition deficits and attenuates oxidative
      stress-related neuronal apoptosis in d-galactose-induced senescent mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Danggui-Shaoyao-San (DSS), a famous traditional
      Chinese medicine formula consisting of six herbal medicines, has been used to
      treat gynecological disorders and neural dysfunctions. AIM OF THE STUDY: The
      present study was carried out to investigate the effects of DSS on cognitive
      ability and oxidative stress-related neuronal apoptosis in the hippocampus of
      aging mice induced by d-galactose (d-gal) to elucidate the underlying molecular
      mechanisms. MATERIALS AND METHODS: Ethanol extract of DSS (DE) were orally
      administered to d-gal-induced senescent mice for six weeks. The cognitive ability
      was determined by the methods of step-down type passive avoidance test and Morris
      water maze test. The activities of superoxide dismutase (SOD) and nitric oxide
      synthase (NOS), and levels of carbonyl protein (CP), glutathione (GSH),
      malondialdehyde (MDA) and nitric oxide (NO) were also examined. Furthermore, the
      expression of apoptotic related proteins in hippocampus of d-gal-treated mice,
      such as Bcl-2, Bax and caspase-3 proteins, were determined by
      immunohistochemistry. RESULTS: DE at the doses of 1.8, 3.6 and 7.2g/kg
      significantly enhanced the cognitive performances and restored the abnormal
      activities of SOD and NOS and levels of CP, MDA, GSH and NO induced by d-gal.
      Moreover, the neural apoptosis in the hippocampus of d-gal-treated mice was
      improved by DE through regulating the expression of Bcl-2, Bax and caspase-3.
      CONCLUSION: These results demonstrate that DE has neuroprotective effects in d
      gal-induced senescent mice by ameliorating oxidative stress induced neuronal
      apoptosis in the brain.

PMID- 22414475
TI  - Effect of Poria cocos on hypertonic stress-induced water channel expression and
      apoptosis in renal collecting duct cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: A major physiological role of the kidney is to
      regulate body water and urine concentration. Aquaporin-2 (AQP2), a family of
      water channels, plays an important role in the urinary concentrating process and
      regulation of water balance in the kidney. The dried sclerotia of Poria cocos
      Wolf has been known to have a diuretic effect and used for the treatment of
      chronic edema and nephrosis. AIM OF THE STUDY: This study was conducted to
      evaluate the inhibitory effect of the sclerotia of Poria cocos (WPC) on
      hypertonic stress-induced AQP2 expression and apoptosis in inner medullary
      collecting duct cell lines (IMCD-3). MATERIALS AND METHODS: Hypertonic stress was
      induced by 175mM NaCl. Inhibitory effect of WPC on hypertonic stress-induced AQP2
      expression and apoptosis were determined by western blot, RT-PCR, and
      immunofluorescence. RESULTS: Hypertonic stress (175mM NaCl) increased in the
      levels of AQP2 expression by hypertonicity in IMCD-3 cells. WPC attenuated the
      hypertonicity-induced increase in protein and mRNA levels of AQP2 in a
      concentration-dependent manner. Pretreatment with WPC attenuated hypertonicity
      induced cell death. Hypertonicity increased serum- and glucocorticoid-inducible
      protein kinase (Sgk1) phosphorylation, however, WPC attenuated the hypertonicity
      induced Sgk1 activation. Tonicity-responsive enhancer binding protein (TonEBP)
      mRNA was also recovered by WPC under hypertonic stress. Pretreatment with WPC
      presented the similar effect of PKA inhibitor which decreased hypertonic stress
      induced AQP2 expression. Hypertonicity increased cAMP levels and the changes were
      blocked by WPC. On the other hand, hypertonic stress-induced Bax or caspase-3
      expression was decreased by WPC, resulting in anti-apoptotic effect. CONCLUSIONS:
      These results provided evidence that the beneficial effect of WPC in water
      balance against in vitro hypertonic stress of renal collecting ducts. In
      addition, WPC exhibits anti-apoptotic property response to hypertonic stress.
      Thus, these data suggests that WPC has benefit for the therapeutic approach to
      the inhibition of renal disorder.

PMID- 22414476
TI  - Anticonvulsant effect of Marsilea quadrifolia Linn. on pentylenetetrazole induced
      seizure: a behavioral and EEG study in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Marsilea quadrifolia Linn (MQ) extract has been
      used traditionally as sedative and antiepileptic drug in India. AIM OF THIS
      STUDY: To investigate the anticonvulsive potential of MQ extracts by using
      behavior and electroencephalographic (EEG) analysis on pentylenetetrazole (PTZ)
      induced seizure model in rats. MATERIALS AND METHODS: For anticonvulsant effect,
      60minutes after administration of MQ, behavior and EEG were analyzed during PTZ
      (60mg/kg) induced seizures. Changes of EEG power, latency of onset of seizure,
      seizure severity score, and duration of epileptic seizure were determined.
      RESULTS: Both the water and ethanol extract of MQ increased the latency of
      seizure but also decreased duration of epileptic seizure and seizure severity
      score. This reduction of seizure severity was also observed in EEG recording and
      EEG power analysis. The effectiveness of MQ ethanol extract is better than MQ
      water extract. CONCLUSION: Both water and ethanol extract of MQ were effective in
      reducing the severity of behavioral and EEG seizures induced by PTZ in rats. This
      study justifies the traditional use of this plant in epilepsy.

PMID- 22414477
TI  - Evaluation of Cameroonian plants towards experimental bone regeneration.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Elephantopus mollis, Spilanthes africana, Urena
      lobata, Momordica multiflora, Asystasia gangetica and Brillantaisia ovariensis
      are used in Cameroonian traditional medicine for the treatment of bone diseases
      and fracture repair. The aim of this study was to evaluate the effect of
      ethanolic extracts of six Cameroonian medicinal plants on bone regeneration
      following bone and marrow injury. MATERIALS AND METHODS: Ethanol extract of
      Cameroonian medicinal plants were administered (each extract at 250, 500 and
      750mg/kg doses) orally to adult female Sprague-Dawley rats having a drill hole
      injury (0.8mm) in the femur diaphysis. Vehicle (gum-acacia in distilled water)
      was given to the control group. After 12 days of treatment, animals were
      euthanized and femur bones collected. Confocal microscopy of fractured bone was
      performed to evaluate bone regeneration (calcein labeling). Only active plant
      extracts were used for further experiments. Thus, callus was analyzed by
      microcomputed tomography. Osteogenic effects of the extracts were evaluated by
      assessing mineralized nodules formation of bone marrow stromal cells and
      osteoblast recruitment at drill hole site by immunohistochemistry. RESULTS:
      Ethanolic extract of the leaves and twigs of Elephantopus mollis (EM) and whole
      plant of Spilanthes africana (SA) dose-dependently stimulated bone regeneration
      at the drill hole site. EM at 250 and 750mg/kg doses and SA at 750mg/kg dose
      significantly increased mineral deposition compared to controls. Both extracts at
      500 and 750mg/kg doses improved microarchitecture of the regenerating bone
      evident from increased bone volume fraction, trabecular thickness, trabecular
      number, and decreased trabecular separation and structure model index. EM and SA
      extracts increased the formation of mineralized nodules from the bone marrow
      stromal cells. In addition, EM and SA extracts increased osteoblast recruitment
      at the drill hole site evident from increased Runx-2 positive cells following
      their treatments compared to control. CONCLUSION: Ethanolic extracts of EM and SA
      accelerate fracture repair in rats via stimulatory effects on osteoblast
      differentiation and mineralization, thereby justifying their traditional use.

PMID- 22414478
TI  - Aqueous fraction from Cuscuta japonica seed suppresses melanin synthesis through
      inhibition of the p38 mitogen-activated protein kinase signaling pathway in
      B16F10 cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Semen cuscutae has been used traditionally to
      treat pimples and alleviate freckles and melasma in Korea. The present study
      aimed to investigate the inhibitory effect of Cuscuta japonica Choisy seeds on
      alpha-melanocyte-stimulating hormone (alpha-MSH)-induced melanogenesis. MATERIALS
      AND METHODS: The aqueous fraction from Semen cuscutae (AFSC) was used to
      determine anti-melanogenic effects by examination of cellular melanin contents,
      tyrosinase activity assay, cAMP assay and Western blot analysis for melanin
      synthesis-related signaling proteins in B16F10 mouse melanoma cells. RESULTS:
      AFSC markedly inhibited alpha-MSH-induced melanin synthesis and tyrosinase
      activity, and also decreased alpha-MSH-induced expression of microphthalmia
      associated transcription factor (MITF) and tyrosinase-related proteins (TRPs).
      Moreover, AFSC significantly decreased the level of phosphorylated p38 mitogen
      activated protein kinase (MAPK) signaling through the down-regulation of alpha
      MSH-induced cAMP. Furthermore, we confirmed that the specific inhibitor of p38
      MAPK (SB203580)-mediated suppressed melanin synthesis and tyrosinase activity was
      further attenuated by AFSC. AFSC also further decreased SB203580-mediated
      suppression of MITF and TRP expression. CONCLUSIONS: These results indicate that
      AFSC inhibits p38 MAPK phosphorylation with suppressed cAMP levels and
      subsequently down-regulate MITF and TRP expression, which results in a marked
      reduction of melanin synthesis and tyrosinase activity in alpha-MSH-stimulated
      B16F10 cells.

PMID- 22414479
TI  - HILIC quantification of oenotheralanosterol A and B from Oenothera biennis and
      their suppression of IL-6 and TNF-alpha expression in mouse macrophages.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Evening primrose (Oenothera biennis L.) is a wild
      medicinal herb of Central American origin that is now globally widespread. Its
      traditional uses include treatment of rheumatoid arthritis and premenopausal pain
      both of which have an inflammatory component. The present study demonstrates the
      in vitro anti-inflammatory activity of three Oenothera biennis compounds.
      MATERIALS AND METHODS: Oenotheralanosterol A and B (Oen-A & Oen-B) along with
      gallic acid (GA) were isolated and characterized using column chromatography and
      NMR. The compounds were tested with LPS stimulated peritoneal mouse macrophages
      assaying for suppression of IL-6, TNF-alpha and NO synthesis. An HILIC method for
      the simultaneous quantitation of GA, Oen-A, and Oen-B in Oenothera biennis plant
      material was also developed as a means of monitoring quality of plant material.
      RESULTS: Significant inhibition of TNF-alpha and IL-6 by GA, Oen-A and Oen-B was
      observed (p<0.05). Inhibition was concentration dependent and no synergistic or
      antagonistic effect on pro-inflammatory cytokines was found when used in
      combination (1:1) (p>0.05). The HILIC analysis method was validated using
      Oenothera biennis root. CONCLUSION: The study demonstrates the anti-inflammatory
      activity of Oenothera biennis root compounds and supports its traditional use in
      arthritis management. Active anti-inflammatory compounds were identified and
      quantified by the HILIC method.

PMID- 22414480
TI  - Antiallergic effects of Scutellaria baicalensis on inflammation in vivo and in
      vitro.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis (SB) is one of the most
      widely used medicinal herbs for the treatment of inflammation. In this study, we
      investigated the antiallergic effect of SB in vivo and in vitro. MATERIALS AND
      METHODS: Sprague-Dawley (SD) rats received intradermal injections of anti-DNP IgE
      at each of three dorsal skin sites. Forty-eight hours later, each rat received an
      injection of DNP-HSA in saline containing 4% Evans blue through the dorsal vein
      of the penis. One hour before injection, SB extract was administered orally. The
      dorsal skin of the rats was removed and the pigment area measured. In addition,
      rat peritoneal mast cells (RPMCs) were cultured and purified to investigate
      histamine release. In vitro, human mast cells (HMC-1) were pretreated with SB
      extract for 30min before stimulation with phorbol 12-myristate 13-acetate (PMA)
      plus A23187. The effects on pro-inflammatory cytokine expression and mitogen
      activated protein (MAP) kinase expression were investigated using TNF-alpha and
      IL-8 assays, and Western blotting analysis of HMC-1 cells. RESULTS AND
      CONCLUSIONS: SB treatment inhibited the passive cutaneous anaphylaxis reaction
      compared to the control group, and histamine release decreased significantly
      following treatment of RPMCs with SB. In HMC-1 cells, SB restored IL-8 and TNF
      alpha expression and inhibited MAP kinase expression in compound 48/80-induced
      HMC-1 cells. These data suggest that SB may prove to be a useful anti
      inflammatory agent through its downregulation of the expression of various
      inflammatory mediators.

PMID- 22414481
TI  - In vitro and in vivo evaluation of the genotoxicity of Gumiganghwal-tang, a
      traditional herbal prescription.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Gumiganghwal-tang (GGT, known as Kumi-Kyokatsu-to
      in Japanese) is a traditional herbal prescription made from nine different herbs
      that is used for the treatment of the common cold, pain, and inflammatory
      diseases. AIM OF THE STUDY: This study evaluated the potential genotoxicity of an
      aqueous GGT extract using three standard battery of tests as part of a safety
      evaluation. MATERIALS AND METHODS: We prepared GGT using a water extraction
      method and subsequently extracted six compounds from GGT by high performance
      liquid chromatography. GGT extract genotoxicity was assayed using three standard
      tests including the in vitro bacterial reverse mutation test, the in vitro
      chromosomal aberration test with Chinese hamster lung cells, and the in vivo
      micronucleus test using ICR mouse bone marrow recommended by the Korean Food and
      Drug Administration. RESULTS: The bacterial reverse mutation assay showed that
      GGT extract doses ranging from 333.3 up to 5000mg/plate induced a greater than 2
      fold increase in the number of revertant TA1537 strain colonies exhibiting
      metabolic activation (with S-9 mix), when compared with the vehicle control. The
      chromosomal aberration test showed that GGT extract induced an increase in the
      number of chromosomal aberrations after treatment for 6h with the S-9 mix and 22h
      without the S-9 mix, when compared with vehicle control. In contrast, the
      micronucleus test showed that GGT extract did not significantly increase the
      number of micronucleated polychromatic erythrocytes (MNPCEs) in ICR mouse bone
      marrow. CONCLUSIONS: Based on these results, it was concluded that GGT extract
      acted as a genotoxic material in our experimental conditions. We did not identify
      the compounds responsible for the induction of genotoxic effects, but it was
      significant that we provided a basic genotoxicity profile for GGT.

PMID- 22414482
TI  - Cellular cholesterol efflux and cholesterol loading capacity of serum: effects of
      LDL-apheresis.
AB  - High LDL-cholesterol (LDL-C) characterizes familial hypercholesterolemia (FH) and
      familial combined hyperlipidemia (FCH). LDL-apheresis, used in these patients to
      reduce LDL-C levels, has been shown to also affect HDL levels and composition. We
      studied LDL-apheresis effects on six FH and nine FCH subjects' serum capacity to
      modulate cellular cholesterol efflux, an index of HDL functionality, and to load
      macrophages with cholesterol. Serum cholesterol efflux capacity (CEC) and
      macrophage cholesterol loading capacity (CLC) were measured before, immediately
      after, and two days after LDL-apheresis. The procedure reduced total cholesterol
      (TC), LDL-C, and apoB plasma levels (-69%, -80% and -74%, respectively),
      parameters only partially restored two days later. HDL-C and apoA-I plasma
      levels, reduced after LDL-apheresis (-27% and -16%, respectively), were restored
      to almost normal levels two days later. LDL-apheresis reduced serum aqueous
      diffusion (AD) CEC, SR-BI-CEC, and ABCA1-CEC. AD and SR-BI were fully restored
      whereas ABCA1-CEC remained low two days later. Sera immediately and two days
      after LDL-apheresis had a lower CLC than pre-LDL-apheresis sera. In conclusion,
      LDL-apheresis transiently reduces HDL-C levels and serum CEC, but it also reduces
      also serum capacity to deliver cholesterol to macrophages. Despite a potentially
      negative effect on HDL levels and composition, LDL-apheresis may counteract foam
      cells formation.

PMID- 22414483
TI  - A simplified procedure for semi-targeted lipidomic analysis of oxidized
      phosphatidylcholines induced by UVA irradiation.
AB  - Oxidized phospholipids (OxPLs) are increasingly recognized as signaling mediators
      that are not only markers of oxidative stress but are also "makers" of pathology
      relevant to disease pathogenesis. Understanding the biological role of individual
      molecular species of OxPLs requires the knowledge of their concentration kinetics
      in cells and tissues. In this work, we describe a straightforward
      "fingerprinting" procedure for analysis of a broad spectrum of molecular species
      generated by oxidation of the four most abundant species of polyunsaturated
      phosphatidylcholines (OxPCs). The approach is based on liquid-liquid extraction
      followed by reversed-phase HPLC coupled to electrospray ionization MS/MS. More
      than 500 peaks corresponding in retention properties to polar and oxidized PCs
      were detected within 8 min at 99 m/z precursor values using a single diagnostic
      product ion in extracts from human dermal fibroblasts. Two hundred seventeen of
      these peaks were fluence-dependently and statistically significantly increased
      upon exposure of cells to UVA irradiation, suggesting that these are genuine
      oxidized or oxidatively fragmented species. This method of semitargeted lipidomic
      analysis may serve as a simple first step for characterization of specific
      "signatures" of OxPCs produced by different types of oxidative stress in order to
      select the most informative peaks for identification of their molecular structure
      and biological role.

PMID- 22414484
TI  - Chimeric relaxin peptides highlight the role of the A-chain in the function of H2
      relaxin.
AB  - Human gene-2 (H2) relaxin is a member of the insulin-relaxin peptide superfamily.
      Because of the potential clinical applications of H2 relaxin, there is a need for
      novel analogs that have improved biological activity and receptor specificity. In
      this respect, we have chemically assembled chimeric peptides consisting of the B
      chain of H2 relaxin in combination with A-chains from other insulin/relaxin
      family members. The peptides were prepared using solid phase peptide synthesis
      together with regioselective disulfide bond formation and characterized by RP
      HPLC, MALDI-TOF MS and amino acid analysis. Their in vitro activity was assessed
      in RXFP1 or RXFP2 expressing cells. Replacement of the H2 relaxin A-chain
      resulted in parallel losses of binding affinity and activity on RXFP1. Not
      surprisingly H1A-H2B demonstrated the highest activity as the H1 A-chain shares
      high homology with H2 relaxin whereas INSLA-H2B, which shows low homology, had
      very poor activity. Importantly A-chain replacements had a dramatic effect on
      RXFP2 activity similar to previous results demonstrating different modes of
      activation of A-chain variants on RXFP1 and RXFP2. H3A-H2B is particularly
      interesting as it displays moderate activity at RXFP1 but poor activity at RXFP2
      indicating that it may be a template for specific RXFP1 agonist development. Our
      study confirms that the activity of H2 relaxin at both RXFP1 and RXFP2 relies on
      interactions with both the B- and A-chains, and also provide new biochemical
      insights into the mechanism of relaxin action that the A-chain needs to be in
      native or near-native form for strong RXFP1 or RXFP2 agonist activity.

PMID- 22414485
TI  - An extended Kalman filtering approach for the estimation of human head tissue
      conductivities by using EEG data: a simulation study.
AB  - In this study, we propose an extended Kalman filter approach for the estimation
      of the human head tissue conductivities in vivo by using electroencephalogram
      (EEG) data. Since the relationship between the surface potentials and
      conductivity distribution is nonlinear, the proposed algorithm first linearizes
      the system and applies extended Kalman filtering. By using a three-compartment
      realistic head model obtained from the magnetic resonance images of a real
      subject, a known dipole assumption and 32 electrode positions, the performance of
      the proposed method is tested in simulation studies and it is shown that the
      proposed algorithm estimates the tissue conductivities with less than 1% error in
      noiseless measurements and less than 5% error when the signal-to-noise ratio is
      40 dB or higher. We conclude that the proposed extended Kalman filter approach
      successfully estimates the tissue conductivities in vivo.

PMID- 22414486
TI  - Practical quantitative and kinetic applications of bio-layer interferometry for
      toxicokinetic analysis of a monoclonal antibody therapeutic.
AB  - Bio-layer interferometry (BLI) is a label-free technology that can be used for
      kinetic characterization of proteins. Although other label-free platforms have
      been used for quantitation purposes (most notably surface plasmon resonance),
      little work has been done using BLI. Here we present rationale and strategies for
      the development and analytical qualification of a BLI assay for the quantitation
      of a humanized antibody therapeutic in cynomolgus monkey plasma. Results of the
      qualification were compared to those of a validated ELISA used to quantitate the
      same therapeutic. Selectivity, matrix effect, and precision and accuracy were
      similar between the two methods. Target interference was more pronounced in the
      BLI assay compared to the ELISA. The main difference between the two assays was
      in the dynamic range (0.1-10 MUg/mL for ELISA vs. 0.4-50 MUg/mL for BLI). The
      monkey plasma BLI assay was applied to rat plasma for the comparison of study
      samples generated in the same matrix by ELISA. A direct quantitation comparison
      of sample results for the two methods shows a high degree of agreement
      (r(2)=0.979, slope=1.017). However, an evaluation of low concentration samples
      showed a bias of over-recovery in the BLI compared to the ELISA. In addition to
      utilizing the quantitative capabilities of the platform, we evaluated the utility
      of using the kinetic properties of the quantitative assay to detect anti-drug
      antibodies (ADA) and illustrated the potential for ADA to cause either over
      recovery (non-neutralizing ADA) or under recovery (neutralizing ADA) of a
      biotherapeutic using the BLI assay.

PMID- 22414487
TI  - Cellular detection of multiple antigens at single cell resolution using
      antibodies generated from the same species.
AB  - Biology at a cellular level comes with a great amount of heterogeneity. It is now
      evident that even clonally propagated cells in an in vitro population do not
      express the same set of cellular epitopes. The vascular endothelial as well as
      blood cells show a very high degree of heterogeneity in expression of specific
      proteins. Although several methods exist for identification of genome or
      transcriptome from a single cell, there is still limited advancement in detection
      of multiple cellular antigens in a single cell. This has been mainly due to the
      limited availability of different antibodies. Single-cell detection methods
      involving the use of multiple monoclonal antibodies generated in the same species
      would therefore provide with an important tool for cellular detection of
      antigens. Here, we describe a method to assess multiple proteins in a cell using
      different antibodies generated in the same species.

PMID- 22414488
TI  - Diagnostic oral food challenges: procedures and biomarkers.
AB  - Oral food challenge (OFC) is the gold standard for the diagnosis of food allergy.
      They are conducted to confirm whether an allergy to food exists (initial
      challenge) or to monitor for resolution of a food allergy. The history of an
      immediate allergic reaction, when supported by positive tests for specific IgE
      antibodies to the suspect food, is often sufficient to establish a diagnosis
      without OFC. Additionally, higher concentrations of food-specific IgE or larger
      allergy prick skin test wheal sizes correlate with an increased likelihood of a
      reaction upon ingestion. Although these food-specific IgE tests are helpful
      biomarkers of allergy, their limited sensitivity and specificity often
      necessitates the use of OFC to establish reactivity. Furthermore, the
      pathogenesis of non-IgE-mediated food allergy, such as food protein-induced
      enterocolitis (FPIES) or proctocolitis and food allergy due to mixed IgE and non
      IgE mediated processes, such as atopic dermatitis or eosinophilic
      gastroenteropathies may not be assessable with specific IgE tests, also
      warranting OFCs. This review provides an overview on the technique and
      interpretation of OFCs, use of food-specific testing to predict whether OFC is
      warranted and to predict OFC outcomes. Additionally, biomarkers that correlate
      with OFC outcomes will be discussed, as well as future diagnostic tests promising
      better predictive value.

PMID- 22414489
TI  - Multiple basal cell carcinomas in a 38-year-old woman with Goltz syndrome.
AB  - BACKGROUND: Focal dermal hypoplasia (FDH) or Goltz syndrome is a rare genetic
      multisystem disorder characterized by hypoplasia of ectodermally and mesodermally
      derived tissues. No cases of development of basal cell carcinomas in patients
      affected by FDH have previously been reported. METHODS: We followed a 38-year-old
      woman with FDH who developed, within a period of 3 years, 14 atypical pigmented
      lesions. All of them were surgically removed and pathologically assessed. In
      2007, this patient underwent molecular examination with the multiple amplifiable
      probe hybridization technique. RESULTS: Histopathological examination showed 6
      basal cell carcinomas, 2 basaloid proliferations, 2 tumours of follicular
      infundibulum and 2 solar lentigines. Molecular examination showed that only 1
      copy of the coding exons of PORCN and EBP, respectively, was present, reflecting
      a microdeletion of one of her X chromosomes, eliminating at least the
      neighbouring genes PORCN and EBP. CONCLUSIONS: No other cases of association
      between FDH and multiple cutaneous basal cell carcinomas have previously been
      reported, so it could be interesting to take into consideration this aspect in
      the molecular assessment of these patients to improve information on the disease.
      This is a single case experience, and especially the molecular results need
      confirmation and validation by other groups involved in the diagnosis.

PMID- 22414490
TI  - Pilot study comparing changes in postural control after training using a video
      game balance board program and 2 standard activity-based balance intervention
      programs.
AB  - OBJECTIVE: To compare the impacts of Tai Chi, a standard balance exercise
      program, and a video game balance board program on postural control and perceived
      falls risk. DESIGN: Randomized controlled trial. SETTING: Research laboratory.
      PARTICIPANTS: Independent seniors (N=40; 72.5+/-8.40) began the training, 27
      completed. INTERVENTIONS: Tai Chi, a standard balance exercise program, and a
      video game balance board program. MAIN OUTCOME MEASURES: The following were used
      as measures: Timed Up & Go, One-Leg Stance, functional reach, Tinetti Performance
      Oriented Mobility Assessment, force plate center of pressure (COP) and time to
      boundary, dynamic posturography (DP), Falls Risk for Older People-Community
      Setting, and Falls Efficacy Scale. RESULTS: No significant differences were seen
      between groups for any outcome measures at baseline, nor were significant time or
      group * time differences for any field test or questionnaire. No group * time
      differences were seen for any COP measures; however, significant time differences
      were seen for total COP, 3 of 4 anterior/posterior displacement and both
      velocity, and 1 displacement and 1 velocity medial/lateral measure across time
      for the entire sample. For DP, significant improvements in the overall score
      (dynamic movement analysis score), and in 2 of the 3 linear and angular measures
      were seen for the sample. CONCLUSIONS: The video game balance board program,
      which can be performed at home, was as effective as Tai Chi and the standard
      balance exercise program in improving postural control and balance dictated by
      the force plate postural sway and DP measures. This finding may have implications
      for exercise adherence because the at-home nature of the intervention eliminates
      many obstacles to exercise training.

PMID- 22414491
TI  - Dissecting kinase profiling data to predict activity and understand cross
      reactivity of kinase inhibitors.
AB  - The development of selective and multitargeted kinase inhibitors has received
      much attention, because cross-reactivity with unintended targets may cause toxic
      side effects, while it can also give rise to efficacious multitargeted drugs.
      Here we describe a deconvolution approach to dissecting kinase profiling data in
      order to gain knowledge about cross-reactivity of inhibitors from large-scale
      profiling data. This approach not only enables activity predictions of given
      compounds on a kinome-wide scale, but also allows to extract residue-fragment
      pairs that are associated with activity. We demonstrate its effectiveness using a
      large-scale public chemogenomics data set and also apply our proposed model to a
      recently published bioactivity data set. We further illustrate that the
      preference of given compounds for kinases of interest is better understood by
      residue-fragment pairs, which could provide both biological and chemical insights
      into cross-reactivity.

PMID- 22414493
TI  - HLA DR15 antigen status does not impact graft-versus-host disease or survival in
      HLA-matched sibling transplantation for hematologic malignancies.
AB  - The HLA class II DRB1 antigen DR15 is an important prognostic marker in immune
      mediated marrow failure states. DR15 has also been associated with favorable
      outcomes (reduced acute graft-versus-host disease [aGVHD] and relapse) after
      allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on
      transplantation outcomes, we conducted a retrospective study of 2891 recipients
      of first allogeneic stem cell transplant from HLA-matched sibling donors for the
      treatment of acute leukemia, chronic myeloid leukemia, or myelodysplastic
      syndrome (MDS) between 1990 and 2007. All patients received conventional
      myeloablative conditioning, T-replete grafts, and cyclosporine plus methotrexate
      based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732
      patients (25.3%) as positive and 2159 patients (74.7%) as negative for DRB1*15:01
      or *15:02 (DR15). There were no significant differences in baseline
      characteristics between the HLA DR15 positive and negative groups. In univariate
      analysis, HLA-DR15 status had no impact on neutrophil engraftment, aGVHD, chronic
      GVHD (cGVHD), treatment-related mortality, relapse, disease-free survival, or
      overall survival (OS). In multivariate analysis, DR15 status showed no
      significant difference in aGVHD, cGVHD, OS, or relapse. In conclusion, DR15
      status had no impact on major HLA-matched sibling donor hematopoietic cell
      transplant outcomes in this large and homogenous cohort of patients with leukemia
      and MDS.

PMID- 22414492
TI  - Roles of histone deacetylases in epigenetic regulation: emerging paradigms from
      studies with inhibitors.
AB  - The zinc-dependent mammalian histone deacetylase (HDAC) family comprises 11
      enzymes, which have specific and critical functions in development and tissue
      homeostasis. Mounting evidence points to a link between misregulated HDAC
      activity and many oncologic and nononcologic diseases. Thus the development of
      HDAC inhibitors for therapeutic treatment garners a lot of interest from academic
      researchers and biotechnology entrepreneurs. Numerous studies of HDAC inhibitor
      specificities and molecular mechanisms of action are ongoing. In one of these
      studies, mass spectrometry was used to characterize the affinities and
      selectivities of HDAC inhibitors toward native HDAC multiprotein complexes in
      cell extracts. Such a novel approach reproduces in vivo molecular interactions
      more accurately than standard studies using purified proteins or protein domains
      as targets and could be very useful in the isolation of inhibitors with superior
      clinical efficacy and decreased toxicity compared to the ones presently tested or
      approved. HDAC inhibitor induced-transcriptional reprogramming, believed to
      contribute largely to their therapeutic benefits, is achieved through various and
      complex mechanisms not fully understood, including histone deacetylation,
      transcription factor or regulator (including HDAC1) deacetylation followed by
      chromatin remodeling and positive or negative outcome regarding transcription
      initiation. Although only a very low percentage of protein-coding genes are
      affected by the action of HDAC inhibitors, about 40% of noncoding microRNAs are
      upregulated or downregulated. Moreover, a whole new world of long noncoding RNAs
      is emerging, revealing a new class of potential targets for HDAC inhibition. HDAC
      inhibitors might also regulate transcription elongation and have been shown to
      impinge on alternative splicing.

PMID- 22414495
TI  - Biologically-induced precipitation of sphalerite-wurtzite nanoparticles by
      sulfate-reducing bacteria: implications for acid mine drainage treatment.
AB  - Several experiments were conducted to evaluate zinc-tolerance of sulfate-reducing
      bacteria (SRB) obtained from three environmental samples, two inocula from
      sulfide-mining districts and another inoculum from a wastewater treatment plant.
      The populations of SRB resisted zinc concentrations of 260 mg/L for 42 days in a
      sulfate-rich medium. During the experiments, sulfate was reduced to sulfide and
      concentrations in solution decreased. Zinc concentrations also decreased from 260
      mg/L to values below detection limit. Both decreases were consistent with the
      precipitation of newly-formed sphalerite and wurtzite, two polymorphs of ZnS,
      forming <2.5-MUm-diameter spherical aggregates identified by microscopy and
      synchrotron-MU-XRD. Sulfate and zinc are present in high concentrations in acid
      mine drainage (AMD) even after passive treatments based on limestone dissolution.
      The implementation of a SRB-based zinc removal step in these systems could
      completely reduce the mobility of all metals, which would improve the quality of
      stream sediments, water and soils in AMD-affected landscapes.

PMID- 22414494
TI  - Predictors of quality of life ratings for persons with dementia simultaneously
      reported by patients and their caregivers: the Cache County (Utah) Study.
AB  - BACKGROUND: Quality of life (QOL) is frequently assessed in persons with dementia
      (PWD) through self- and/or proxy-report. Determinants of QOL ratings are
      multidimensional and may differ between patients and caregiver proxies. This
      study compared self- and proxy-reported QOL ratings in a population-based study
      of PWD and their caregivers, and examined the extent to which discrepancies in
      reports were associated with characteristics of the PWD. METHODS: The sample
      consisted of 246 patient/caregiver dyads from the initial visit of the Cache
      County Dementia Progression Study, with both members of the dyad rating PWD QOL.
      PWD age, gender, cognitive impairment (Mini-Mental State Examination),
      neuropsychiatric symptoms (Neuropsychiatric Inventory; NPI), dementia severity
      (Clinical Dementia Rating), medical comorbidities (General Medical Health
      Rating), and functional impairment (Dementia Severity Rating Scale) were examined
      as correlates of self- and proxy-reported QOL ratings and the differences between
      the QOL reports. RESULTS: Self- and proxy-reported PWD QOL ratings were only
      modestly correlated. Medical comorbidity was associated with self-report whereas
      NPI was associated with proxy-report. Dementia severity was associated with
      discrepancies in self- and proxy-report, with worse patient cognition associated
      with poorer proxy-reported QOL ratings. CONCLUSIONS: PWD self- and proxy-reported
      QOL ratings are associated with different variables. Discrepancies between PWD
      and caregiver perceptions of PWD QOL should be recognized, particularly in cases
      of more severe dementia.

PMID- 22414496
TI  - Comparative evaluation of environmental contamination and DNA damage induced by
      electronic-waste in Nigeria and China.
AB  - In the last decade, China and Nigeria have been prime destinations for the
      world's e-waste disposal leading to serious environmental contamination. We
      carried out a comparative study of the level of contamination using soils and
      plants from e-waste dumping and processing sites in both countries. Levels of
      polyaromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and
      polybrominated diphenyl ethers (PBDEs) were analyzed using gas
      chromatography/spectrophotometry and heavy metals using atomic absorption
      spectrophotometry. DNA damage was assayed in human peripheral blood lymphocytes
      using an alkaline comet assay. Soils and plants were highly contaminated with
      toxic PAHs, PCBs, PBDEs, and heavy metals in both countries. Soil samples from
      China and plant samples from Nigeria were more contaminated. There was a positive
      correlation between the concentrations of organics and heavy metals in plant
      samples and the surrounding soils. In human lymphocytes, all tested samples
      induced significant (p<0.05) concentration-dependent increases in DNA damage
      compared with the negative control. These findings suggest that e-waste
      components/constituents can accumulate, in soil and surrounding vegetation, to
      toxic and genotoxic levels that could induce adverse health effects in exposed
      individuals.

PMID- 22414498
TI  - Surviving stress.

PMID- 22414497
TI  - Virulence of Streptococcus pneumoniae serotype 6C in experimental otitis media.
AB  - Increases in colonization with serotypes of Streptococcus pneumoniae not
      contained within the 7-valent pneumococcal conjugate vaccine (PCV) have been
      reported among children following introduction. Serotype 6C has emerged as
      prevalent in nasopharyngeal colonization and acute otitis media (AOM), though it
      is uncommonly recovered from children with invasive pneumococcal disease. Vaccine
      serotypes within PCV7 have been replaced by nonvaccine serotypes without
      significant changes in the overall carriage rate. We hypothesize 1) that
      serotypes vary in their ability to evade host defenses and establish AOM
      following colonization and 2) the observed reduction in pneumococcal otitis
      results from a reduced disease potential by some 'replacement serotypes'. We
      compared the capacity of S. pneumoniae serotypes 6C and 19A to produce
      experimental otitis media (EOM) in a chinchilla model. The proportion of
      chinchillas that developed culture positive EOM and density of middle ear
      infection was evaluated. EOM was found in 28/82 (34%) ears challenged with 6C
      compared to 13/18(72.2%) with 19A [p = 0.0003]. When disease due to 6C did occur,
      it was characterized by low-density infection. Our findings demonstrate that
      challenge with serotype 6C results in EOM less frequently than 19A. These data
      support the need for greater knowledge regarding differences among serotypes to
      produce AOM.

PMID- 22414499
TI  - Ketorolac nasal spray--a new formulation of this non-narcotic pain reliever.

PMID- 22414500
TI  - Multidisciplinary treatment of maxillary central incisors: a case report.

PMID- 22414501
TI  - Provisional cements--are they getting better?

PMID- 22414502
TI  - To treat or not to treat...that is the question.

PMID- 22414503
TI  - Duplicating the form and function of posterior teeth with Class II resin-based
      composite.
AB  - The most common material used to fill Class II restorations in posterior teeth is
      resin-based composite (RBC). Despite the popularity of RBC restorations, there
      are challenges to placing them properly. Improperly shaped restorations with
      sharp edges and corners will chip and fracture, resulting in premature failure.
      Properly placed RBC restorations will duplicate the embrasures, contact area,
      marginal ridge, and occlusal fossa of natural teeth. RBC restorations should
      mimic the smooth and rounded contours of the natural dentition to ensure
      longevity.

PMID- 22414504
TI  - The influence of composite resin restorations and lining on radiographic
      diagnosis and decision-making: an in vitro investigation.
AB  - The objective of this study was to evaluate the influence of resin-based
      restorations on the interpretation of digital and conventional radiographic
      images and to correlate the proposed diagnosis with decision-making. Class II
      cavities were prepared in one of the proximal surfaces of extracted human molars.
      Teeth were divided into five groups (n = 10) according to the restoratives used:
      Natural Flow (NF) and Filtek Supreme (FS); Filtek Flow (FF) and FS; Tetric Flow
      (TF) and FS; Protect Liner F (PLF) and FS; and FS alone. Bitewing radiographs
      were taken using conventional and digital systems. Subjective analysis was
      performed for each surface: no restoration; restored teeth; or restored teeth
      with gap. Based on the given diagnosis, clinical conduct was then indicated.
      Material radiopacity was determined according to ISO 4049. A Fisher exact test
      evaluated the influence of the restoratives on the diagnosis. Means were compared
      using ANOVA and the Games-Howell test. A Friedman test was used to analyze the
      influence of the systems on the diagnosis, and a binomial test was used to
      analyze the association between the presence of gaps and the decision to replace
      the restoration (P = 0.05).  For each system, TF+FS was significantly associated
      with a high percentage of correct diagnoses. The opposite was the case for
      PLF+FS, which differed from all other groups. Radiographic systems presented
      similar behaviors, except for NF+FS. Apart from PLF, adequate radiopacity was
      observed. Diagnosis was influenced by restorative materials, regardless of the
      radiographic system used. The low radiopacity of PLF led to a greater number of
      erroneous diagnoses. Moreover, the decision-making process was influenced
      strongly by the given diagnosis.

PMID- 22414505
TI  - The influence of master cast technique on the cast precision of implant-retained
      fixed prostheses.
AB  - The aim of this study was to evaluate the precision of three different mold
      filling techniques in order to obtain a cast simulating a three-unit, implant
      retained, fixed prosthesis. Thirty casts (n = 10) were obtained using three
      different mold filling techniques. Group 1 used a unique fulfillment technique,
      Group 2 used a two-step fulfillment technique, and Group 3 used a latex cylinder
      technique. Using a metallic matrix, a titanium substructure was created to
      simulate a three-unit fixed prosthesis used as reference to evaluate the marginal
      misfit and tension forces in each cast. The vertical misfit was measured by an
      optical microscope with an increase of 120X and by an analysis unit using the one
      screw test. The tension was quantified using strain gauges.  The strain results
      showed a statistical difference between Group 3 and the other groups. The Tukey
      test showed no difference between the different treatment groups (p = 0.05). All
      three techniques were deemed efficient; however, considering that the cylinder
      latex technique induced less force toward the implants, it is the preferable
      technique for daily clinical practice.

PMID- 22414506
TI  - Basic principles of maximizing dental office productivity.
AB  - To maximize office productivity, dentists should focus on performing tasks that
      only they can perform and not spend office hours performing tasks that can be
      delegated to non-dentist personnel. An important element of maximizing
      productivity is to arrange the schedule so that multiple patients are seated
      simultaneously in different operatories. Doing so allows the dentist to work on
      one patient in one operatory without needing to wait for local anesthetic to take
      effect on another patient in another operatory, or for assistants to perform
      tasks (such as cleaning up, taking radiographs, performing prophylaxis, or
      transporting and preparing equipment and supplies) in other operatories. Another
      way to improve productivity is to structure procedures so that fewer steps are
      needed to set up and implement them. In addition, during procedures, four-handed
      dental passing methods can be used to provide the dentist with supplies or
      equipment when needed. This article reviews basic principles of maximizing dental
      office productivity, based on the author's observations of business logistics
      used by various dental offices.

PMID- 22414507
TI  - Impact of surface finishes on the flexural strength and fracture toughness of In
      Ceram Zirconia.
AB  - Dental restorations made of zirconia are usually selectively adjusted chairside
      to eliminate occlusal or internal interferences that can impair the mechanical
      properties of ceramic framework material. Effects of polishing procedures on
      zirconia after chipping or simply glazing the monolithic zirconia restorations
      are not known. This study evaluated the effects of different surface treatment
      procedures--namely, glazing or grinding, finishing, and polishing regimens--on
      the flexural strength and fracture toughness of a zirconia core material. Forty
      zirconia specimens were prepared and divided into two main groups (n = 20)
      according to the type of surface treatment (glazed or ground, finished, and
      polished). Each group was further divided into two subgroups (n = 10) according
      to type of mechanical test (flexural strength and fracture toughness). The
      roughness measurements were performed before mechanical testing. Qualitative
      evaluation of representative specimens of each subgroup was performed using SEM.
      The surface roughness mean (MUm; +/- standard deviations) recorded for the glazed
      specimens (0.94 +/- 0.2) was significantly lower than that of the finished and
      polished group (3.01 +/- 0.1) (P < 0.05). The glazed zirconia showed
      significantly higher flexural strength (385.4 +/- 45.4 MPa) and fracture
      toughness (6.07 +/- 1 MPa.m1/2) values than the ground, finished, polished
      zirconia (302.4 +/- 47.6 MPa and 2.14 +/- 0.5 MPa.m1/2) (P = 0.002 and P < 0.001
      for flexural strength and fracture toughness, respectively). A smooth topographic
      pattern after glazing could not be obtained after finishing and polishing.
      Grinding, finishing, and polishing markedly decreased the flexural strength and
      fracture toughness of zirconia compared to the glazed groups.

PMID- 22414508
TI  - Effectiveness of LANAP over time as measured by tooth loss.
AB  - This study examines the effectiveness of the laser-assisted new attachment
      procedure (LANAP) as measured by tooth loss, comparing data to published studies
      using conventional surgical treatment modalities for the primary treatment of
      Types III and IV periodontitis.  Retrospective data from 107 patients presenting
      with Types III and IV periodontitis were gathered and evaluated. All patients
      received LANAP periodontal therapy as their primary surgical treatment according
      to the FDA-cleared LANAP protocol. The patients averaged 6.2 years post
      treatment. The data were compared to several published studies for outcome
      classification and tooth loss over time.  The effectiveness of LANAP as a primary
      treatment method for Types III and IV periodontitis compares very favorably with
      conventional surgical treatment modalities concerning tooth loss and stability
      over time, need for surgical retreatment, and outcome classification.  Dentistry
      continues to develop less invasive means of providing patient care without
      sacrificing results. Less invasive treatment of periodontitis, with reduced
      postoperative morbidity yet equal results in tooth retention over time is an
      important goal. LANAP treatment for moderate and advanced periodontitis provides
      a less invasive treatment alternative for the dentist and patient to consider as
      a part of informed consent.

PMID- 22414509
TI  - Residual oxygen releasing time from dental structure after carbamide peroxide
      exposure: study of the effects of a neutralizer gel.
AB  - The purpose of this article was to assess in vitro the effects of a catalase
      based neutralizer gel in the release of residual oxygen in permanent human teeth
      specimens exposed to 10% carbamide peroxide. Thirty teeth specimens (5.0 x 5.0 x
      3.0 mm3) were randomly divided into three groups (n = 10): Group 1, nonbleached
      negative control specimens; Group 2, bleached positive control specimens; and
      Group 3, bleached specimens exposed to a catalase-based gel. The bleaching
      treatment was performed six hours per day for 14 days. At the end of the
      bleaching treatment, Group 3 specimens were immersed in a receptacle containing
      the catalase-based experimental gel for three minutes. Titrations were performed
      to determine the quantity of residual oxygen that each test specimen released,
      starting immediately after the end of the bleaching treatment and exposure (or
      not) to the catalase-based gel, and repeated on days 1-5, 10, and 15. The values
      obtained were statistically analyzed by ANOVA and a Tukey post hoc test (P <
      0.05).  The release values of residual O2 for Group 2 were equal to those of
      Group 1 after 10 days and to those of Group 3 after five days. The use of a
      catalase-based experimental neutralizer gel, applied for three minutes, reduced
      by half the time required for complete release of residual oxygen from tooth
      structure after exposure to a 10% carbamide peroxide bleaching agent.

PMID- 22414510
TI  - Expansile mass in the edentulous mandible. Cemento-osseous dysplasia.

PMID- 22414511
TI  - Painless red lesion on the tongue. Pyogenic granuloma.

PMID- 22414512
TI  - Crown-root fracture of fused primary teeth--a case report.
AB  - In the primary dentition, traumatic injuries affecting the tooth-supporting
      structures are common due to increased bone resilience in children. Crown-root
      fracture, defined as a fracture involving enamel, dentin, and cementum, is
      uncommon in the primary dentition, comprising only 2% of dental traumas. This
      article reports the treatment and follow-up of a 2-year-old boy who suffered a
      traumatic crown-root fracture involving a primary anterior incisor that was fused
      to a supernumerary tooth.

PMID- 22414513
TI  - Shear bond strength of new self-adhesive flowable composite resins.
AB  - Recently, new self-adhesive flowable composite resin systems have been introduced
      to the market. These new composite resin systems reportedly bond to dentin and
      enamel without the application of an adhesive bonding agent. The purpose of this
      study was to evaluate the shear bond strength to enamel of two new self-adhesive
      flowable composites with and without the use of an etch-and-rinse bonding agent.
      The new self-adhesive flowable composites had significantly lower bond strengths
      to enamel compared to a traditional adhesively bonded flowable composite. Both
      self-adhesive flowable composites had a significant increase in bond strength to
      enamel with the use of a phosphoric acid-etch and adhesive bonding agent.

PMID- 22414514
TI  - Mandibular desmoplastic ameloblastoma: case report.
AB  - Desmoplastic ameloblastoma (DA) is a tumor characterized by unique clinical,
      radiological, and histopathologic features, mostly an abundance of densely
      collagenous stroma with small nests and islands of odontogenic epithelium. Due to
      its aggressive, highly invasive nature, there is a tendency to treat DA with bone
      resection. This article reports and discusses an uncommon case of mandibular DA,
      focusing on the importance of early, effective treatment.

PMID- 22414515
TI  - Orthodontic treatment of a child with Crigler-Najjar syndrome type I using
      tacrolimus following liver transplantation.
AB  - The present study reports the orthodontic treatment of a child with Crigler
      Najjar syndrome type I following a liver transplant and administration of
      tacrolimus (1 mg/day). Tacrolimus (FK506) is fundamental to immunosuppression
      following transplantation. The child exhibited Class II division 1 malocclusion.
      The treatment option was to use a Herbst appliance for seven months and a fixed
      appliance (straight wire) for 12 months.

PMID- 22414516
TI  - Physiotherapy as an adjuvant therapy for treatment of TMJ disorders.
AB  - Physiotherapy has long been used to cure joint and muscle diseases. It has also
      been used to treat various diseases without inflicting mental trauma or the pain
      of surgery. This adjunctive therapeutic modality is widely used for patients with
      orofacial disorders, especially in the prevention or treatment of
      temporomandibular joint (TMJ) disorder, hypomobility, or ankylosis. Physiotherapy
      has a particular importance in the treatment of TMJ disorders such as myofascial
      pain and internal derangement. This review article highlights the importance of
      physiotherapy as an emerging adjuvant therapy in the treatment of TMJ disorders.

PMID- 22414517
TI  - Esthetic and functional combination of fixed and removable prostheses.
AB  - When creating optimally esthetic contemporary prosthetic restorations, clinicians
      should balance patient preferences and requests with functional and esthetic
      demands. Beyond fulfilling the treatment objectives of restoring function and
      optimizing esthetics, the combination of fixed and removable dental prostheses
      should also blend seamlessly into the oral environment.  Treatment planning and
      proper design of the prostheses is of paramount importance, while knowledge of
      material science and laboratory steps is needed to guarantee successful execution
      of clinical procedures. This article provides methods and techniques for
      improvement of the esthetic outcome through the description of clinical and
      laboratory steps of a clinical case.

PMID- 22414518
TI  - Evaluating EDTA as a substitute for phosphoric acid-etching of enamel and dentin.
AB  - Matrix metalloproteinases (MMPs) are proteolytic enzymes released when dentin is
      acid-etched. The enzymes are capable of destroying unprotected collagen fibrils
      that are not encapsulated by the dentin adhesive. Chlorhexidine applied after
      etching inhibits the activation of released MMPs, whereas neutral ethylenediamine
      tetra-acetic acid (EDTA) prevents the release of MMPs. The purpose of this study
      was to determine if conditioning enamel and dentin with EDTA can be a substitute
      for treating acid-etching enamel and dentin with chlorhexidine. A column of
      composite resin was bonded to enamel and dentin after conditioning. Shear bond
      strengths were evaluated after 48 hours and after accelerated aging for three
      hours in 12% sodium hypochlorite.  Shear bond strengths ranged from 15.6 MP a for
      accelerated aged EDTA enamel specimens to 26.8 MPa for dentin conditioned with
      EDTA and tested after 48 hours. A three-way ANOVA and a Tukey HSD test found
      statistically significant differences among the eight groups and the three
      independent variables (P < 0.05). EDTA was successfully substituted for
      phosphoric acid-etched enamel and dentin treated with chlorhexidine. Interactions
      of conditioning agent and aging were significant for dentin but not for enamel.
      In an effort to reduce the detrimental effects of MMPs, conditioning enamel and
      dentin with EDTA is an alternative to treating acid-etched dentin and enamel with
      chlorhexidine.

PMID- 22414520
TI  - Clinical efficacy of tetracaine anesthetic paste.
AB  - Benzocaine, the most commonly used topical anesthetic in dentistry, often fails
      to eliminate the pain associated with injections. One type of anesthetic used
      frequently in medicine with success is tetracaine, but minimal research has been
      done regarding the application of tetracaine in dentistry. This study sought to
      evaluate the effectiveness and safety of tetracaine anesthetic paste (TAP), a
      newly formulated topical anesthetic. For this study, TAP was applied to the
      maxillary mucobuccal fold of one side of the arch and benzocaine paste was
      applied to the opposite side prior to injection of anesthetic. Patients then
      reported the level of pain experienced on each side and were evaluated for any
      adverse reactions. The results showed no difference in effectiveness between TAP
      and benzocaine paste, and no adverse reactions were reported. Because of the
      safety and effectiveness of tetracaine extraorally, further research is warranted
      on its intraoral use.

PMID- 22414519
TI  - Fracture strength of endodontically treated teeth restored with different
      strategies after mechanical cycling.
AB  - The aim of this study was to analyze the fracture strength of endodontically
      treated teeth with different coronal restoration strategies after mechanical
      cycling. Thirty bovine teeth were randomly allocated into three groups (n = 10):
      Group 1, cast metal post and core; Group 2, glass fiber post with a composite
      resin core; Group 3, glass fiber post with a glass prefabricated core. For post
      cementation, an etch and rinse multistep adhesive system and resin cement were
      used. The specimens were submitted to mechanical cycling (106 cycles, 90 N, 4 Hz,
      37 +/- 1 degree C) and immediately loaded in a universal testing machine. The
      statistical analysis (one-way ANOVA) did not indicate a significant difference
      among the tested groups (Group 1 = 593.9 +/- 128.7 N; Group 2 = 554.4 +/- 213.3
      N; Group 3 = 427 +/- 104.8 N; P = 0.06). With regard to fracture patterns, all
      Group 1 specimens demonstrated catastrophic failures, while the specimens in
      Groups 2 and 3 demonstrated core or core/post failure. Despite the similar
      fracture strength observed in the tested groups, teeth restored with composite
      resin or glass prefabricated cores demonstrated favorable failure patterns
      compared to the cast metal post and core group. This study demonstrates that a
      glass prefabricated core can be an acceptable alternative for the reconstruction
      of endodontically treated teeth.

PMID- 22414521
TI  - Chloroquine-induced hyperpigmentation of the hard palate.
AB  - This article reports a rare case of extensive palatal pigmentation secondary to
      long-term chloroquine treatment. Chloroquine was originally used as an
      antimalarial agent, but it is now widely used as an adjunct in the treatment of
      autoimmune diseases. Adverse effects of chloroquine usually include skin changes
      such as bullous pemphigoid, exacerbation of psoriasis, and pigmentation of the
      skin and mucous membranes as well as retinopathy, gastrointestinal alterations,
      and neuromuscular disorders. Extensive oral pigmentation is an uncommon feature
      of an adverse drug effect, and diagnosis should be based on clinicopathological
      findings.

PMID- 22414522
TI  - Influence of acid-etching and ceramic primers on the repair of a glass ceramic.
AB  - The objective of this study was to evaluate the influence of different primers on
      the microtensile bond strength (MUTBS) between a feldspathic ceramic and two
      composites. Forty blocks (6.0 x 6.0 x 5.0 mm3) were prepared from Vita Mark II .
      After polishing, they were randomly divided into 10 groups according to the
      surface treatment: Group 1, hydrofluoric acid 10% (HF) + silane; Group 2, CoJet +
      silane; Group 3, HF + Metal/Zirconia Primer; Group 4, HF + Clearfil Primer; Group
      5, HF + Alloy Primer; Group 6, HF + V-Primer; Group 7, Metal/Zirconia Primer;
      Group 8, Clearfil Primer; Group 9, Alloy Primer; Group 10, V-Primer. After each
      surface treatment, an adhesive was applied and one of two composite resins was
      incrementally built up. The sticks obtained from each block (bonded area: 1.0 mm2
      +/- 0.2 mm) were stored in distilled water at 37 degrees C for 30 days and
      submitted to thermocycling (7,000 cycles; 5 degrees C/55 degrees C +/- 1 degree
      C). The MUTBS test was carried out using a universal testing machine (1.0
      mm/min). Data were analyzed using ANOVA and a Tukey test (a = 0.05). The surface
      treatments significantly affected the results (P < 0.05); no difference was
      observed between the composites (P > 0.05). The bond strength means (MPa) were as
      follows: Group 1a = 29.6; Group 1b = 33.7; Group 2a = 28.9; Group 2b = 27.1;
      Group 3a = 13.8; Group 3b = 14.9; Group 4a = 18.6; Group 4b = 19.4; Group 5a =
      15.3; Group 5b = 16.5; Group 6a = 11; Group 6b = 18; Groups 7a to 10b = 0. While
      the use of primers alone was not sufficient for adequate bond strengths to
      feldspathic ceramic, HF etching followed by any silane delivered higher bond
      strength.

PMID- 22414523
TI  - Antral membrane elevation using a post graft: a crestal approach.
AB  - The crestal approach to elevating the antral membrane by a resorbable StemVie
      post is a modification of the sinus lift technique. This technique can add 4-10
      mm of bone height for severely atrophic ridges in areas that are difficult to
      access through a lateral window. The procedure is minimally invasive, simple, and
      predictable, and has less postoperative morbidity due to smaller flap design and
      minimal osteotomy. If sufficient alveolar bone is present for stabilization, an
      implant can be placed simultaneously with an antral elevation and graft. The
      StemVie post resorbs completely and is replaced by the patient's own bone.
      Healing is enhanced with the addition of bone marrow aspirate and/or peripheral
      venous blood to the StemVie post graft. The graft will absorb the blood or the
      marrow, allowing them to infiltrate through the porosity present in the graft.
      Bone marrow aspirate aids in healing with the addition of precursor osteoblastic
      stem cells, cytokines, and growth factors, while peripheral blood supplies mostly
      cytokines and growth factors.

PMID- 22414524
TI  - Orthograde retreatment failure with extruded MTA apical plug in a large
      periradicular lesion followed by surgical intervention: case report.
AB  - Absence of periapical healing after orthograde retreatment using an apical plug
      with mineral trioxide aggregate (MTA) can require surgical intervention. A
      patient with a root-filled maxillary central incisor with chronic apical
      periodontitis and sinus tract was referred for endodontic retreatment. Excessive
      apical enlargement was verified, indicating an MTA apical plug placement;
      however, an unintentional extrusion of MTA occurred during this step. The root
      canal was filled with gutta-percha and sealer, and periodic recalls were
      scheduled. The sinus tract was observed after six months and the lesion remained
      unaltered, although the extruded MTA had resorbed; therefore, an apicoectomy and
      retrograde root-end filling with MTA were performed. Absence of sinus tract,
      normal clinical aspect, and complete repair of the lesion were observed at the
      two-year follow-up.

PMID- 22414525
TI  - The assessment of changes in cognitive functioning in the elderly: age- and
      education-specific reliable change indices for the SIDAM.
AB  - BACKGROUND/AIMS: The diagnostic criteria for dementia include reliable evidence
      of cognitive deterioration over time measured by cognitive tests. The Structured
      Interview for the Diagnosis of Dementia of the Alzheimer Type, Multi-infarct
      Dementia and Dementia of other Etiology according to DSM-III-R, DSM-IV and ICD-10
      (SIDAM) is a neuropsychological instrument to determine cognitive status in
      patients with mild cognitive impairment (MCI) and dementia. Normative data for
      changes in cognitive functioning that normally occur in cognitively healthy
      individuals are required to interpret changes in SIDAM test scores. METHODS: A
      sample of 1,090 cognitively healthy individuals participating in the German Study
      on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe) aged 75
      years and older was assessed four times at 1.5-year intervals over a period of
      4.5 years using the SIDAM. Age- and education-specific reliable change indices
      (RCIs) accounting for probable measurement error and practice effects were
      computed for a 90% confidence interval. RESULTS: Across different age and
      education subgroups, changes from at least 3-5 points indicated significant (i.e.
      reliable) changes in SIDAM test scores at the 90% confidence level. CONCLUSION:
      This study offers age- and education-specific normative data for the SIDAM based
      upon established RCI methods. The RCI scores provided in this study may help
      clinicians and researchers to interpret cognitive changes in SIDAM test scores
      and may contribute to the early detection and diagnosis of MCI and dementia in
      the elderly.

PMID- 22414526
TI  - Evaluation of scientific programs at a large-scale academic congress: lessons
      from the 22nd World Congress of Dermatology.
AB  - BACKGROUND: The organization of a scientific program and the arrangement of the
      speakers require a considerable amount of time and effort. However, little is
      known about how to reinforce the participants' satisfaction with scientific
      programs at a large-scale academic congress with multiple parallel sessions.
      OBJECTIVES: This study had three main purposes: (1) to create a reference for
      future congresses, (2) to determine session popularity and participation rate,
      and (3) to identify which characteristics of sessions can affect the perception
      of the audience. METHODS: A total of 216 scientific sessions during the 22nd
      World Congress of Dermatology were evaluated using printed evaluation surveys.
      RESULTS: The average scores for all sessions and speakers were relatively high.
      There were significant differences in the numbers of total session scores,
      collected surveys and speakers for each session category. The number of speakers
      at each session was not related to the session results. It was found that among
      the three different session grades (excellent, fair and poor), the proportion of
      speakers of each grade especially contributed to the perceived quality of the
      poor-grade sessions. CONCLUSIONS: This survey will help to organize scientific
      sessions and improve the quality of academic congresses.

PMID- 22414527
TI  - Impact of anesthesia on pathophysiology and mortality following subarachnoid
      hemorrhage in rats.
AB  - BACKGROUND: Anesthesia is indispensable for in vivo research but has the
      intrinsic potential to alter study results. The aim of the current study was to
      investigate the impact of three common anesthesia protocols on physiological
      parameters and outcome following the most common experimental model for
      subarachnoid hemorrhage (SAH), endovascular perforation. METHODS: Sprague-Dawley
      rats (n = 38) were randomly assigned to (1) chloral hydrate, (2) isoflurane or
      (3) midazolam/medetomidine/fentanyl (MMF) anesthesia. Arterial blood gases,
      intracranial pressure (ICP), mean arterial blood pressure (MAP), cerebral
      perfusion pressure (CPP), and regional cerebral blood flow (rCBF) were monitored
      before and for 3 hours after SAH. Brain water content, mortality and rate of
      secondary bleeding were also evaluated. RESULTS: Under baseline conditions
      isoflurane anesthesia resulted in deterioration of respiratory parameters
      (arterial pCO2 and pO2) and increased brain water content. After SAH, isoflurane
      and chloral hydrate were associated with reduced MAP, incomplete recovery of post
      hemorrhagic rCBF (23 +/- 13% and 87 +/- 18% of baseline, respectively) and a high
      anesthesia-related mortality (17 and 50%, respectively). Anesthesia with MMF
      provided stable hemodynamics (MAP between 100-110 mmHg), high post-hemorrhagic
      rCBF values, and a high rate of re-bleedings (> 50%), a phenomenon often observed
      after SAH in humans. CONCLUSION: Based on these findings we recommend anesthesia
      with MMF for the endovascular perforation model of SAH.

PMID- 22414528
TI  - Impact of gender on snore-based obstructive sleep apnea screening.
AB  - Obstructive sleep apnea syndrome (OSA) is a serious widespread disease in which
      upper airways (UA) are collapsed during sleep. OSA has marked male predominance
      in prevalence. Although women are less vulnerable to OSA, under-diagnosed OSA in
      women may associate with serious consequences. Snoring is commonly associated
      with OSA and one of the earliest symptoms. Snore sounds (SS) are generated due to
      vibration of the collapsing soft tissues of the UA. Structural and functional
      properties of the UA are gender dependent. SS capture these time varying gender
      attributed UA properties and those could be embedded in the acoustic properties
      of SS. In this paper, we investigate the gender-specific acoustic property
      differences of SS and try to exploit these differences to enhance the snore-based
      OSA detection performance. We developed a snore-based multi-feature vector for
      OSA screening and one time-measured neck circumference was augmented. Snore
      features were estimated from SS recorded in a sleep laboratory from 35 females
      and 51 males and multi-layer neural network-based pattern recognition algorithms
      were used for OSA/non-OSA classification. The results were K-fold cross
      validated. Gender-dependent modeling resulted in an increase of around 7% in
      sensitivity and 6% in specificity at the decision threshold AHI = 15 against a
      gender-neutral model. These results established the importance of adopting gender
      specific models for the snore-based OSA screening technique.

PMID- 22414529
TI  - Specific phosphorylation of alphaA-crystallin is required for the alphaA
      crystallin-induced protection of astrocytes against staurosporine and C2-ceramide
      toxicity.
AB  - We previously reported that alphaA-crystallin and protease-activated receptor are
      involved in protection of astrocytes against C2-ceramide- and staurosporine
      induced cell death (Li et al., 2009). Here, we investigated the molecular
      mechanism of alphaA-crystallin-mediated cytoprotection. We found that the
      expression of mutants mimicking specific phosphorylation of alphaA-crystallin
      increases the protection of astrocytes. However, the expression of mutants
      mimicking unphosphorylation of alphaA-crystallin results in loss of protection.
      These data revealed that the phosphorylation of alphaA-crystallin at Ser122 and
      Ser148 is required for protection. Furthermore, we explored the mechanism of
      cytoprotection of astrocytes by alphaA-crystallin. Application of specific
      inhibitors of p38 and ERK abrogates the protection of astrocytes by over
      expression of alphaA-crystallin. Thus, p38 and ERK contribute to protective
      processes by alphaA-crystallin. This is comparable to our previous results which
      demonstrated that p38 and ERK regulated protease-activated receptor-2 (PAR
      2)/alphaB-crystallin-mediated cytoprotection. Furthermore, we found that PAR-2
      activation increases the expression of alphaA-crystallin. Thus, endogenous alphaA
      crystallin protects astrocytes via mechanisms, which regulate the expression
      and/or phosphorylation status of alphaA-crystallin.

PMID- 22414530
TI  - A personal view from a long-lasting collaborator on the research strategies of
      Marshall Nirenberg.
AB  - In this review, I summarized transition in Dr. Marshall Nirenberg's research
      interests during 1970s, from a view of a long-lasting collaborator. Nirenberg
      switched his research filed to neurobiology after his success in deciphering
      genetic code and being honored with the Nobel Prize in Physiology or Medicine in
      1968. His targets were to obtain genetically pure population of neurons, i.e.
      neuroblastoma clones, to make somatic hydrid cells, to culture neuronal and
      muscle cells, and to produce monoclonal antibodies against whole retinal or
      neuroblastoma cells. He studied neurotransmitters, receptors, cyclic nucleotides,
      cell differentiation, secretion, synapse formation, and chemical recognition.
      Especially he liked his hypothesis for opiate tolerance and dependency as a model
      of cellular memory. Through these studies, he seemed to devote all his time of
      about 50 years from 1960s to decoding brain memory processes.

PMID- 22414532
TI  - Molecular analysis of central feeding regulation by neuropeptide Y (NPY) neurons
      with NPY receptor small interfering RNAs (siRNAs).
AB  - Hypothalamic neuropeptides play important roles in central feeding behavior.
      Among them, neuropeptide Y (NPY) has the strongest orexigenic action. It is
      synthesized in NPY-expressing neurons in the arcuate nucleus (ARC), which
      projects to other nuclei, mainly to the paraventricular nucleus (PVN). PVN, which
      possesses NPY-Y1, -Y2 and -Y4, -Y5 receptors, is considered as feeding center for
      central feeding behavior. Herein I review recent results on feeding behavior
      obtained by gene knockdown technologies. The small interfering RNA (siRNA)
      plasmid-based vectors, which drive transcription of siRNA by U6 RNA polymerase
      III promoter to produce knockdown of the NPY and its receptor (Y1, Y2, Y4 and Y5)
      genes, were stereotaxically injected into mouse ARC and PVN. Feeding behaviors
      were measured for 6days after siRNA vector injection. NPY and its receptor mRNA
      levels were decreased, which were measured by RT-PCR and in situ hybridization,
      and simultaneous decrease in their proteins was also detected in separate nuclei
      by immunohistochemistry. In the NPY system, decrease in NPY, Y1 and Y5
      expressions in specialized nuclei diminished central feeding behavior, whereas
      decrease in Y2 or Y4 expression in both ARC or PVN did not affect feeding
      behavior. Thus, specialized change in expressions of NPY and its receptors
      (especially Y1 and Y5) are important for regulation of endogenous feeding
      behavior in central regulation. Further analysis of NPY receptors may provide
      better understanding of feeding behavior and of potential therapeutic targets.

PMID- 22414531
TI  - The role of agrin in synaptic development, plasticity and signaling in the
      central nervous system.
AB  - Development of the neuromuscular junction (NMJ) requires secretion of specific
      isoforms of the proteoglycan agrin by motor neurons. Secreted agrin is widely
      expressed in the basal lamina of various tissues, whereas a transmembrane form is
      highly expressed in the brain. Expression in the brain is greatest during the
      period of synaptogenesis, but remains high in regions of the adult brain that
      show extensive synaptic plasticity. The well-established role of agrin in NMJ
      development and its presence in the brain elicited investigations of its possible
      role in synaptogenesis in the brain. Initial studies on the embryonic brain and
      neuronal cultures of agrin-null mice did not reveal any defects in
      synaptogenesis. However, subsequent studies in culture demonstrated inhibition of
      synaptogenesis by agrin antisense oligonucleotides or agrin siRNA. More recently,
      a substantial loss of excitatory synapses was found in the brains of transgenic
      adult mice that lacked agrin expression everywhere but in motor neurons. The
      mechanisms by which agrin influences synapse formation, maintenance and
      plasticity may include enhancement of excitatory synaptic signaling, activation
      of the "muscle-specific" receptor tyrosine kinase (MuSK) and positive regulation
      of dendritic filopodia. In this article I will review the evidence that agrin
      regulates synapse development, plasticity and signaling in the brain and discuss
      the evidence for the proposed mechanisms.

PMID- 22414533
TI  - Bloodstream infections in cystic fibrosis: nine years of experience in both
      adults and children.
AB  - BACKGROUND: We report the aetiology and outcome of bloodstream infections (BSI)
      occurring at two regional cystic fibrosis (CF) centres (one adult, one
      paediatric) between 1998 and 2006. METHODS: A retrospective analysis of all
      positive blood cultures during the study period was performed. RESULTS: During
      the study period 1691 blood culture sets were taken. Fifty-seven clinically
      significant episodes of BSI in 48 people with CF (36 adult, 12 paediatric) were
      identified, along with 28 other episodes considered to be contamination or not
      clinically significant. The most common BSIs were caused by coagulase-negative
      staphylococci (13) Candida spp (10), and Stenotrophomonas maltophilia (8). The
      majority (82%) of significant BSIs were considered to originate from totally
      implantable vascular access devices (TIVADs); only 9% were attributed to the
      lower respiratory tract. The TIVAD was removed in two-thirds of cases of TIVAD
      associated BSI. There were three deaths (60% of cases) attributable to BSI
      originating from the lower respiratory tract but no deaths attributable to TIVAD
      associated BSI. CONCLUSION: Most significant BSIs in patients with CF originate
      from TIVADs. Targeted antimicrobial therapy and appropriate early device removal
      is associated with good clinical outcome. BSI originating from the lower
      respiratory tract is associated with poor clinical outcome.

PMID- 22414534
TI  - Calcium signaling in developing embryos: focus on the regulation of cell shape
      changes and collective movements.
AB  - During morphogenesis tissues significantly remodel by coordinated cell migrations
      and cell rearrangements. Central to this problem are cell shape changes that are
      driven by distinct cytoskeletal reorganization responsible for force generation.
      Calcium is a versatile and universal messenger that is implicated in the
      regulation of embryonic development. Although calcium transients accrue clearly
      and more intensely in tissues undergoing rearrangement/migration, it is far from
      clear what the role of these calcium signals is. Here we summarize the evidence
      implicating calcium participation in tissue movements, cell shape changes and the
      reorganization of contractile cytoskeletal elements in developing embryos. We
      also discuss a novel hypothesis that short-lived calcium spikes are required in
      cells and tissues undergoing migration and rearrangements as a fine tuning
      response mechanism to prevent local, abnormally high fluctuations in cytoskeletal
      activities.

PMID- 22414536
TI  - Optical imaging of concealed brain activity using a gold mirror in honeybees.
AB  - Brain activity is inherently combinatorial and three-dimensional. Optical imaging
      techniques offer a suitable opportunity to record many activity foci
      simultaneously, but under conventional microscopy conditions, optical access is
      generally limited to the frontal part of the brain. Thus, even for cases in which
      optical recordings have delivered substantial data, our knowledge of deeper
      layers is deficient. Using the honeybee olfactory system as a test system, we
      report that by using a gold-sputtered cover slip as a minute mirror, it is
      possible to optically access and record from otherwise inaccessible brain areas.
      In insects, the first brain area to code for odors is the antennal lobe
      (comparable to the vertebrate olfactory bulb). Several previous studies have
      characterized glomerular odor response patterns of the frontal view, readily
      accessible when the head capsule of the bee is opened. However, until now, the
      back and the sides of the antennal lobe have remained utterly unexplored. This is
      particularly relevant because in the honeybee these two views coincide with two
      separate olfactory subsystems, related to two axonal tracts of second-order
      neurons: the lAPT and the mAPT. Combining wide-field microscopy, calcium imaging,
      and a minute mirror, we report the first glomerular odor responses from the side
      of the honeybee antennal lobe.

PMID- 22414535
TI  - Attractive guidance: how the chemokine SDF1/CXCL12 guides different cells to
      different locations.
AB  - During the development and adult life of multicellular organisms cells move from
      one location to another as they assemble into organs, seal a wound or fight
      pathogens. For navigation, migrating cells follow cues that guide them to their
      final position. Frequently, a single cue simultaneously guides different cells to
      different positions. Recent studies of one such cue-the chemokine SDF1-suggest
      strategies for how the animal achieves this task without causing erroneous
      migration.

PMID- 22414537
TI  - Dopaminergic system as the mechanism underlying personality in a beetle.
AB  - Individuals in many animal species exhibit 'personality,' consistent differences
      in behaviour across time, situations and/or contexts. Previous work has revealed
      a negative genetic correlation between intensity of tonic immobility and walking
      activity levels in the confused flour beetle, Tribolium confusum, thus suggesting
      these beetles exhibit personality in activity-related traits. The present study
      investigated the mechanism underlying this correlation. We used individuals
      derived from two strains established via artificial divergent selection for
      duration of tonic immobility. "Long" (L) strains exhibited higher frequencies and
      longer durations of tonic immobility, and lower activity levels, while "Short"
      (S) strains exhibited lower frequencies and shorter durations of tonic immobility
      and higher activity levels. We found that the duration of tonic immobility, and
      activity level, could be altered by caffeine administration; L strains fed with
      caffeine exhibited decreased durations of tonic immobility and increased activity
      levels. We also found that brain dopamine levels were lower in L strains than in
      S strains. Consequently, this study demonstrates that the dopaminergic system
      plays an important part in controlling the genetic correlation between tonic
      immobility and activity levels in this species.

PMID- 22414538
TI  - Increase of 30K protein in identified motoneurons by hemolymph results in
      inhibition of programmed cell death in silkworm, Bombyx mori (Lepidoptera,
      Bombycidae).
AB  - This study demonstrates that a 30K protein was gradually synthesized in primary
      cultured motoneurons from the accessory planta retractor (APR) of the 6th
      abdominal ganglion (APR6) in silkworm ventral ganglia through stimulation of
      hemolymph. An increase in 30K protein synthesis resulted in an inhibition of
      programmed cell death (PCD) of APR6 motoneurons. The 30K protein was gradually
      synthesized from the 30Kc6 gene of identified APR6s in day-6 4th instars to day-9
      5th instar larvae, but synthesis of the 30K protein ceased in isolated APR6s of
      day-1 pupa, which normally begin to undergo PCD. When pupal APR6s were treated
      with larval hemolymph, however, the 30K protein was synthesized suggesting the
      existence of an anti-PCD factor in the larval hemolymph. An increase of 30K
      protein within the APR6s was confirmed by antiserum made against the recombinant
      30K protein that originated from the APR 30Kc6 gene. Larval APR6, in which PCD
      was induced with 20-hydroxyecdysone (20E) added to the primary culture, exhibited
      some PCD characteristics of shrinkage of cell bodies, axonal fragmentation and
      loss of mitochondrial function. These results provide new insights on the
      survival or PCD of insect motoneurons through stimulation of hemolymph.

PMID- 22414539
TI  - Student nurses as school nurse extenders.
AB  - The severe underuse of school nurses leaves students with unaddressed health
      needs that impact their safety and learning ability. An undergraduate pediatric
      clinical focusing on nursing students and the role of a school nurse in an
      elementary school setting can be a unique approach to combining the needs of
      school children and educating student nurses. One school of nursing created such
      a project to help address these needs and collect data on the activities student
      nurses performed in school nurse role and their impact on student health. This
      project serves as both a practice improvement project and an innovation in
      pediatric clinical education. The purposes of this project were to quantify
      baccalaureate nursing student activities related to the school nurse role and to
      evaluate the results that have the potential to impact on student health in an
      urban elementary school.

PMID- 22414540
TI  - Telephone follow-up for pediatric ambulatory surgery: parent and provider
      satisfaction.
AB  - Traditional 4- to 6-week clinic follow-up after pediatric ambulatory surgery does
      not rapidly identify complications and is often a burden for parents. Telephone
      follow-up offers support and is preferred in a variety of adult populations, but
      there is little research in pediatrics to support this practice. This article
      describes a practice change involving a standardized telephone follow-up protocol
      by a pediatric nurse practitioner to parents within 1 week of their child's
      ambulatory surgery. An interview survey method was used to evaluate parent
      satisfaction with telephone follow-up and desire for a clinic visit. Staff
      satisfaction and resource utilization are also described.

PMID- 22414541
TI  - Positive components of mental health provide significant protection against
      likelihood of falling in older women over a 13-year period.
AB  - BACKGROUND: In late life, falls are associated with disability, increased health
      service utilization and mortality. Physical and psychological risk factors of
      falls include falls history, grip strength, sedative use, stroke, cognitive
      impairment, and mental ill-health. Less understood is the role of positive
      psychological well-being components. This study investigated the protective
      effect of vitality on the likelihood of falls in comparison to mental and
      physical health. METHODS: Female participants were drawn from the Dynamic
      Analyses to Optimise Ageing (DYNOPTA) harmonization project. Participants (n =
      11,340) were aged 55-95 years (Mean = 73.68; SD = 4.31) at baseline and observed
      on up to four occasions for up to 13 years (Mean = 5.30; SD = 2.53). RESULTS: A
      series of random intercept logistic regression models consistently identified
      vitality's protective effects on falls as a stronger effect in the reduction of
      the likelihood of falls than the effect of mental health. Vitality is a
      significant predictor of falls likelihood even after adjusting for physical
      health, although the size of effect is substantially explained by its covariance
      with mental and physical heath. CONCLUSIONS: Vitality has significant protective
      effects on the likelihood of falls. In comparison with mental health, vitality
      reported much stronger protective effects on the likelihood to fall in comparison
      with the risk associated with poor mental health in a large sample of older
      female adults. Both physical health and mental health account for much of the
      variance in vitality, but vitality still reports a protective effect on the
      likelihood of falls.

PMID- 22414542
TI  - Pathological changes in tight junctions and potential applications into
      therapies.
AB  - Epithelial cells are pivotal in the separation of the body from the outside
      environment. Orally administered drugs must pass across epithelial cell sheets,
      and most pathological organisms invade the body through epithelial cells. Tight
      junctions (TJs) are sealing complexes between adjacent epithelial cells.
      Modulation of TJ components is a potent strategy for increasing absorption.
      Inflammation often causes disruption of the TJ barrier. Molecular imaging
      technology has enabled elucidation of the dynamics of TJs. Molecular pathological
      analysis has shown the relationship between TJ components and molecular
      pathological conditions. In this article, we discuss TJ-targeted drug development
      over the past 2 years.

PMID- 22414543
TI  - Catechins containing a galloyl moiety as potential anti-HIV-1 compounds.
AB  - Catechins containing galloyl moieties are important natural antioxidant
      compounds. In this paper, we review the multiple mechanisms whereby catechins
      containing a galloyl moiety can target key proteins to inhibit sexual
      transmission of HIV-1, as well as HIV-1 fusion, HIV-1 reverse transcriptase, HIV
      1 integrase and HIV-1 protease. Furthermore, catechins with a galloyl moiety can
      mediate host cell factors such as nitric oxide synthase, nuclear factor-kappaB
      and casein kinase II to inhibit HIV-1 infection. The most significant inhibitory
      effect is blocking gp120 binding to isolated human CD4+ T cells. The multiple
      mechanisms underlying the anti-HIV activity of galloyl-containing catechins
      predict that these catechins could be used as alternative therapies in the
      treatment of HIV infection.

PMID- 22414544
TI  - R&D investments for neglected diseases can be sensitive to the economic goal of
      pharmaceutical companies.
AB  - A fundamental problem with neglected diseases is how to induce pharmaceutical
      companies to invest resources for developing effective treatments. A recent
      debate focused on the role of economic incentives represented by monetary
      transfers to the firms. In this article I focus on the economic goals of
      pharmaceutical companies, as determinants for R&D effort. In particular, within a
      stylized framework, the work compares expected profit and expected productivity
      maximization, arguing that the former in general induces higher R&D investments
      than the latter. Therefore, as it is currently the case, when pharmaceutical
      firms focus on productivity, appropriate economic incentives might be needed for
      them to invest in R&D for neglected diseases.

PMID- 22414545
TI  - Risk factors for intra-abdominal infection after pancreaticoduodenectomy - a
      retrospective analysis to evaluate the significance of preoperative biliary
      drainage and postoperative pancreatic fistula.
AB  - BACKGROUND/AIMS: Intra-abdominal infection (IAI) after pancreaticoduodenectomy
      (PD) is a common cause of prolongation of postoperative hospital stay and
      readmission to the hospital following discharge. METHODOLOGY: Two hundred and six
      patients undergoing PD were reviewed to investigate the risk factors for IAI
      after PD. Patients were separated into two groups: those who developed IAI after
      PD (Group A; n=44), and those who had not developed IAI after PD (Group B;
      n=162), the two groups were then compared to identify the risk factors for IAI
      after PD. A hundred and six patients (51.5%) underwent preoperative biliary
      drainage (PBD). RESULTS: Multivariate analysis revealed that pancreatic fistula
      (PF) was an independent risk factor for IAI after PD (p<0.001; odds ratio=9.58;
      95% confidence interval=4.37-21.0), but PBD was not a significant risk factor.
      CONCLUSIONS: We demonstrated that the adequate PBD might not affect IAI after PD.
      On the other hand, PF was an independent risk factor for IAI after PD. A large
      randomized controlled trial, which would prove the effect of early removal of a
      prophylactic placed drain to prevent IAI, should be planned.

PMID- 22414546
TI  - Endoscopic approach for postoperative complications following laparoscopic
      assisted gastrectomy in early gastric cancer: literature review.
AB  - BACKGROUND/AIMS: Laparoscopic-assisted gastrectomy (LAG) is a minimal invasive
      surgery for stomach cancer. The endoscopic approach for postoperative
      complications could reduce re-operation. The aim of our study is to investigate
      the efficacy of endoscopic procedures and postoperative complications of LAG.
      METHODOLOGY: A total of 393 patients who underwent LAG for early gastric cancer
      were included retrospectively. Technical and clinical success of endoscopic
      procedures and the relationship between postoperative complications and the types
      of resection and anastomosis were evaluated. RESULTS: The mean age of patients
      was 58 years old and the number of men was 250 (63.8%). Forty five complications
      occurred in 37 patients (11.5%). Early (within 1 month) and late (after 1 month)
      postoperative complications occurred in 30 (7.7%) and 6 (1.5%) patients,
      respectively. Endoscopic procedures were performed for intraluminal bleeding,
      anastomotic leakage and anastomotic stenosis. Clinical and technical success of
      endoscopic procedures was 100% (16/16) and 93.8% (15/16) respectively. The
      occurrence of anastomotic leakage and anastomotic stenosis were significantly
      high in LATG and Roux-en-Y group than LADG and Billroth-I, and LADG and Billroth
      II groups. CONCLUSIONS: Our study showed that endoscopic procedures could
      effectively control postoperative anastomotic complications. Anastomotic leakage
      and stenosis occurred more frequently in patients who underwent LATG with Roux-en
      Y anastomosis.

PMID- 22414547
TI  - Decreased expression of T-cadherin is associated with gastric cancer prognosis.
AB  - BACKGROUND/AIMS: To investigate the expression status of truncated-cadherin (T
      cadherin) and its clinicopathological significance in gastric cancer.
      METHODOLOGY: Expression status of T-cadherin was detected in a total of 103
      surgical specimens of gastric cancer and 34 corresponding normal gastric tissues
      by real-time qPCR, western blotting and immunohistochemistry. Correlation between
      the expression of T-cadherin and clinicopathological factors of gastric cancer
      was analyzed. RESULTS: T-cadherin mRNA levels were significantly reduced in 29
      (85.3%) tumor tissue samples, compared with levels in the adjacent normal tissue
      samples (p<0.01). This finding was confirmed by western blotting analysis
      (p<0.01) and immunohistochemistry analysis (p<0.01). Larger tumor size (diameter
      >4cm), lymph node metastasis, invasion into surrounding tissues, poor
      differentiation and higher TNM stage of carcinoma were significantly correlated
      with decreased expression of T-cadherin (p<0.05 or p<0.01). Univariate Cox
      regression analysis showed that smaller tumor size (diameter =4cm), none lymph
      node metastasis, none invasion into surrounding tissues, well-differentiation,
      lower TNM stage and higher expression of T-cadherin were closely associated with
      increased overall survival (p<0.05 or p<0.01). Multivariate Cox regression
      analysis showed that positive expression of T-cadherin was a most important
      independent risk factor in gastric cancer. CONCLUSIONS: Expression of T-cadherin
      is an important independent prognostic predictor, which can be used as a
      biomarker of progression and prognosis in gastric cancer.

PMID- 22414549
TI  - Portal vein anastomosis with parachute method in hepatectomy and pancreatectomy.
AB  - In advanced cancers of hepatobiliary and pancreatic lesions, major vascular
      resection and reconstruction are necessary to accomplish curative resection.
      Stenosis of vascular anastomosis is a concern in case of portal or superior
      mesenteric venous anastomosis with different vascular calibers. We attempted to
      apply parachute anastomosis in such a situation, which has often been used in the
      field of cardiovascular surgery. We applied this procedure in 4 cases of two
      hepatectomies in intrahepatic cholangiocarcinomas and two pancreatectomies in
      pancreatic carcinomas, in which combined vascular resection was necessary. After
      anastomosis, the orifice of anastomotic veins was well matched and did not show
      stenosis or poor blood flow on ultrasonographic examination. Parachute
      anastomosis in the portal or superior mesenteric vein is a useful procedure to
      prevent vascular stenosis, particularly in case of anastomosis with different
      calibers.

PMID- 22414548
TI  - Correlations between clinicopathological parameters and molecular signatures of
      primary tumors for patients with stage T3n0 colorectal adenocarcinomas: a single
      center retrospective study on 100 cases.
AB  - BACKGROUND/AIMS: To examine the clinical and protein expression characteristics
      of tumor tissues for prediction of prognosis in colorectal cancer (CRC).
      METHODOLOGY: We retrospectively analyzed the clinicopathological data of patients
      with stage T3N0 CRC, operated between 1997-2003 and the surgical materials for
      the relation between disease prognosis and p53, p21, p16, beta-catenin, E
      cadherin, EGFR, hMLH1, hMSH2 and TS protein expressions. RESULTS: A significantly
      shorter 3-year disease free survival was observed in patients under the age of
      50. The worst 5-year overall survival (OS) observed for patients over 70. Tumor
      localization and number of processed lymph nodes significantly affected
      prognosis. The EGFR, hMSH2 and TS expressions and the 5-fluorouracyl treatment
      were not found to be of prognostic value; p53 and p21 positivity had
      significantly worse survival. When beta-catenin membrane expression disappeared
      on tumor cells, the 5-year OS rate decreased and time to metastasis shortened
      significantly. Membrane beta-catenin expression, processed lymph nodes number and
      age were detected as independent prognostic markers. CONCLUSIONS: These results
      suggest that the evaluation of a clinicopathological profile, based on age, tumor
      localization, number of examined lymph nodes, p53, p21 and E-cadherin beta
      catenin expression appears to be useful in identifying high risk patients.

PMID- 22414550
TI  - Alzheimer's disease: genetic polymorphisms and rate of decline.
AB  - BACKGROUND/AIM: To investigate the influence of established genetic risk factors
      for Alzheimer's disease on the speed of disease progression. METHODS:
      Polymorphisms (in ACE, ApoE, BIN1, CLU, CR1, CST3, EXOC3L2, GWA14q32.13, IL8,
      LDLR, PICALM, TNK1) of 40 Alzheimer's disease patients from a longitudinal study
      were analyzed. A standardized loss of Mini-Mental State Examination points was
      used as the progression parameter. RESULTS: Polymorphisms in CST3 and EXOC3L2 as
      well as the absence of APOE4 were associated with more aggressive disease
      courses. A trend was observed for BIN1. CONCLUSION: In addition to being a risk
      factor for disease development, some of the polymorphisms investigated here are
      associated with higher rates of decline and disease progression and thus might
      act as prognostic disease markers. This effect needs to be considered in future
      treatment strategies.

PMID- 22414551
TI  - Delayed beneficial effect of acute exercise on red blood cell aggregate strength
      in patients with sickle cell anemia.
AB  - Because of the metabolic changes induced by a physical activity, the
      hemorheological properties of patients with sickle cell anemia could be further
      impaired and increase the risks for vaso-occlusive complications. However, few
      studies suggest that moderate physical activity could be beneficial rather than
      harmful in patients with sickle cell anemia (SCA). However, the definition of
      what can be considered as a moderate physical activity in SCA patients is
      imprecise. The present study tested the effects of a short incremental cycling
      exercise test conducted until the first ventilatory threshold on different
      biomarkers. Hematological and hemorheological parameters were compared between 8
      patients with SCA and 13 healthy subjects (CONT) before, immediately after the
      end of the exercise and at 12, 36 and 60 hours after the exercise. We observed no
      significant hematological or hemorheological alteration induced by the exercise
      in the two groups. However, the exercise resulted in a delayed improvement of the
      red blood cell disaggregation threshold at 36 and 60 hrs after exercise in the
      SCA group which was paralleled to the decrease in the platelet count in this
      group. The present study suggests that such an exercise might be beneficial for
      microcirculatory blood flow.

PMID- 22414552
TI  - Beyond virological suppression: the role of adherence in the late HAART era.
AB  - HAART has increased the life expectancy of HIV-infected individuals
      significantly. Optimal adherence to HAART results in viral suppression and immune
      recovery in the majority of HIV-infected persons. Data from the early HAART era
      suggest that adherence levels of greater than 95% are necessary to achieve and
      maintain virological suppression. However, the optimal threshold of adherence
      required to maximize the pharmacological benefits of contemporary antiretroviral
      regimens, particularly in the virologically suppressed patient, is unknown. This
      review examines new data on the role of adherence in the late HAART era, focusing
      on virological, immunological and epidemiological aspects. We begin with a
      discussion of the impact of adherence on viral dynamics and immunological
      parameters in the virologically suppressed patient. We then review the importance
      of adherence in emerging antiretroviral treatment strategies. Finally, we
      summarize accumulating data on the role of antiretroviral adherence in the
      prevention of HIV transmission. Taken together, the data reviewed reinforce the
      critical importance of adherence in the management of HIV infection in the late
      HAART era.

PMID- 22414553
TI  - Bioinformatics as a driver, not a passenger, of translational biomedical
      research: Perspectives from the 6th Benelux bioinformatics conference.
AB  - The 6th Benelux Bioinformatics Conference (BBC11) held in Luxembourg on 12 and
      13 December 2011 attracted around 200 participants, including internationally
      renowned guest speakers and more than 100 peer-reviewed submissions from 3
      continents. Researchers from the public and private sectors convened at BBC11 to
      discuss advances and challenges in a wide spectrum of application areas. A key
      theme of the conference was the contribution of bioinformatics to enable and
      accelerate translational and clinical research. The BBC11 stressed the need for
      stronger collaborating efforts across disciplines and institutions. The
      demonstration of the clinical relevance of systems approaches and of next
      generation sequencing-based measurement technologies are among the existing
      opportunities for increasing impact in translational research. Translational
      bioinformatics will benefit from research models that strike a balance between
      the importance of protecting intellectual property and the need to openly access
      scientific and technological advances. The full conference proceedings are freely
      available at http://www.bbc11.lu.

PMID- 22414554
TI  - Prevalence of water pipe use and its correlates in Iranian women of reproductive
      age in Tehran: a population-based study.
AB  - OBJECTIVE: The objective of this study was to determine the prevalence of water
      pipe smoking and its associated sociodemographic factors among Iranian women of
      reproductive age in Tehran. SUBJECTS AND METHODS: This was a population-based
      cross-sectional study of 1,359 Iranian women aged 15-49 years. The multistage
      random cluster technique was used to obtain the sample. Questionnaire-based
      interviews with questions relating to water pipe smoking and sociodemographic
      variables were used to collect the data. The multivariate logistic regression
      model was used to analyse the relationships between the dependent variable (water
      pipe smoking) and the independent variables (sociodemographic characteristics).
      RESULTS: The prevalence of water pipe smoking was 6.3% among Iranian women. Water
      pipe smoking was more likely in the age range of 15-24 years [odds ratio (OR) =
      4.8, 95% confidence interval (95% CI) = 2.7-8.6] compared to the age range of 35
      years or older, in women with a university education (OR = 1.9, 95% CI = 1.3-3.0)
      compared to women with a high-school diploma or lower, and in women with an
      average crowding index score (OR = 4.7, 95% CI = 2.1-10.6) compared to women
      living in small families. CONCLUSION: The findings of this study show that
      Iranian women with a university education and the younger age group (15-24 years)
      were at most risk of water pipe smoking. The findings of this study about
      associated factors may contribute to the development of efficient health
      promotion programmes for the prevention and cessation of water pipe smoking.

PMID- 22414555
TI  - Umbilical cord mesenchymal stem cells suppress B-cell proliferation and
      differentiation.
AB  - Mesenchymal stem cells (MSCs) may be obtained from umbilical cord as an abundant
      and noninvasive source. However, the immunomodulatory properties of umbilical
      cord-MSCs (UC-MSCs) were poorly studied. In this study, we aimed to investigate
      the effects of UC-MSCs on B-cell proliferation and differentiation. UC-MSCs were
      found to suppress the proliferation of B cells isolated from murine spleen.
      Moreover, UC-MSCs markedly suppressed B-cell differentiation as shown by the
      decreased number of CD138+cells and reduced levels of IgM and IgG production in
      coculture. As revealed by transwell experiments, soluble factors produced by UC
      MSCs might be involved in mediating B-cell suppression. The Blimp-1 mRNA
      expression was suppressed whereas the PAX-5 mRNA expression was induced in
      coculture. Finally, UC-MSCs modified the phosphorylation pattern of Akt and p38
      pathways, which were involved in B-cell proliferation and differentiation. These
      results may further support the potential therapeutic use of UC-MSCs in treating
      autoimmune disorders.

PMID- 22414556
TI  - Mathematical modelling of transformations of asymmetrically distributed
      biological data: an application to a quantitative classification of spiny neurons
      of the human putamen.
AB  - Many measurements in biology follow distributions that can be approximated well
      by the normal distribution. The normal distribution plays an extremely important
      role in probability theory. However, some of the experimental data in biology are
      distributed asymmetrically. In order to transform such an asymmetrical
      distribution into a normal distribution, for which the standard statistical
      tables can be used for probability analysis of the available data, one must
      choose suitable transformation functions. We have met this problem when we
      qualitatively classified the spiny neurons in the adult human putamen. But, if
      one tries to test a qualitative classification of neurons quantitatively, a
      considerable class overlap between cells occurs as well as asymmetry often
      appears in the distributions of the data. We have already offered a method to
      overcome the overlapping problem when the data distributions are normal. In order
      to resolve the asymmetry problem in data distribution, we transformed our
      asymmetrically distributed data into an approximately normal distribution using a
      family of simple power functions and on a basis of appropriate probability
      analysis we propose a more acceptable classification scheme for the spiny
      neurons. The significance of our results in terms of current classifications of
      neurons in the adult human putamen is discussed.

PMID- 22414557
TI  - DNA repair as a biomarker. Foreword.

PMID- 22414558
TI  - A single-dose cytomegalovirus-based vaccine encoding tetanus toxin fragment C
      induces sustained levels of protective tetanus toxin antibodies in mice.
AB  - The current commercially available vaccine used to prevent tetanus disease
      following infection with the anaerobic bacterium Clostridium tetani is safe and
      effective. However, tetanus remains a major source of mortality in developing
      countries. In 2008, neonatal tetanus was estimated to have caused >59,000 deaths,
      accounting for 1% of worldwide infant mortality, primarily in poorer nations. The
      cost of multiple vaccine doses administered by injection necessary to achieve
      protective levels of anti-tetanus toxoid antibodies is the primary reason for low
      vaccine coverage. Herein, we show that a novel vaccine strategy using a
      cytomegalovirus (CMV)-based vaccine platform induces protective levels of anti
      tetanus antibodies that are durable (lasting >13 months) in mice following only a
      single dose. This study demonstrates the ability of a 'single-dose' CMV-based
      vaccine strategy to induce durable protection, and supports the potential for a
      tetanus vaccine based on CMV to impact the incidence of tetanus in developing
      countries.

PMID- 22414559
TI  - Dextran sulfate sodium-induced ulcerative colitis leads to increased
      hematopoiesis and induces both local as well as systemic genotoxicity in mice.
AB  - Ulcerative colitis is a chronic gastrointestinal disorder eliciting the risk of
      colorectal cancer, the third most common malignancy in humans. The present study
      was aimed to characterize dextran sulfate sodium-induced ulcerative colitis and
      to elucidate its influence on the bone marrow cell proliferation and the
      subsequent stimulation of the systemic genotoxicity in mice. Experimental colitis
      was induced in Swiss mice using 3% (w/v) dextran sulfate sodium in drinking
      water. The severity of colitis was assessed on the basis of clinical signs, colon
      length, oxidative stress parameters, various pro-inflammatory markers,
      histopathological evaluation and immunohistochemical staining of 8-oxo-7,8
      dihydro-2'-deoxyguanosine in the colon of dextran sulfate sodium treated mice.
      Further, assessment of genotoxicity was carried out using alkaline and modified
      comet assays in the colon and lymphocytes and micronucleus assay in the
      peripheral blood of mice. For the evaluation of inflammation-induced cell
      proliferation in the bone marrow, proliferating cell nuclear antigen
      immunostaining was carried out in the bone marrow of mice. Dextran sulfate sodium
      induced severe colitis as evident from the elevated disease activity index,
      reduced colon length, increased oxidative stress, histological abnormalities and
      oxidative DNA damage in the colon of mice. Moreover, colitis-induced elevated
      prostaglandin-E2 level in the plasma of dextran sulfate sodium treated mice
      stimulated the cell proliferation in the bone marrow, which further triggered
      colitis-induced DNA damage in the peripheral blood of mice.

PMID- 22414560
TI  - Retrotransposon insertions in rice gene pairs associated with reduced
      conservation of gene pairs in grass genomes.
AB  - Small-scale changes in gene order and orientation are common in plant genomes,
      even across relatively short evolutionary distances. We investigated the
      association of retrotransposons in and near rice gene pairs with gene pair
      conservation, inversion, rearrangement, and deletion in sorghum, maize, and
      Brachypodium. Copia and Gypsy LTR-retrotransposon insertions were found to be
      primarily associated with reduced frequency of gene pair conservation and an
      increase in both gene pair rearrangement and gene deletions. SINEs are associated
      with gene pair rearrangement, while LINEs are associated with gene deletions.
      Despite being more frequently associated with retrotransposons than convergent
      and tandem pairs, divergent gene pairs showed the least effects from that
      association. In contrast, convergent pairs were least frequently associated with
      retrotransposons yet showed the greatest effects. Insertions between genes were
      associated with the greatest effects on gene pair arrangement, while insertions
      flanking gene pairs had significant effects only on divergent pairs.

PMID- 22414561
TI  - Family structure and income during the stages of childhood and subsequent
      prosocial behavior in young adulthood.
AB  - This study investigated whether family structure transition and low income are
      risk factors in the development of prosocial behavior. Models of young adults'
      prosocial behavior - charitable giving and volunteering - were estimated as
      functions of their family structure and income during the stages of childhood.
      Participants were a representative sample of 1011 American young adults. In the
      full sample, family structure transition during adolescence was negatively
      associated with subsequent charitable giving in young adulthood. Low income
      during adolescence was negatively associated with both giving and volunteering in
      young adulthood. European-American young men also exhibited a negative
      association between family structure transition during adolescence and subsequent
      volunteering. The results did not seem to describe African-American young adults.
      Keeping this qualification in mind, the results suggest that adolescence is a
      sensitive stage in the development of charitable giving and volunteering.

PMID- 22414562
TI  - Physical restraint use in institutional care of old people in Sweden in 2000 and
      2007.
AB  - BACKGROUND: Physical restraint use is common in institutional care for old people
      and mainly used to prevent falls, despite the fall-preventive effect of physical
      restraints being questioned in previous research. The aim of the study was to
      investigate the use of physical restraints in Sweden in 2000 and 2007. METHODS:
      Data were collected from two comparable census surveys conducted in all
      institutional care units for old people in 2000 (n = 3,669) and 2007 (n = 2,914).
      Information on residents' characteristics and physical restraint use was
      collected using the Multi-Dimensional Dementia Assessment Scale (MDDAS). RESULTS:
      In 2000 16.0% (95% confidence interval (CI) 14.8%-17.2%) of the residents were
      restrained compared to 18.2% (95% CI 16.8%-19.6%) in 2007 (p = 0.017). Adjusting
      for residents' characteristics showed that residents in 2007 were more likely to
      be physically restrained, relative to the residents in 2000 (odds ratio (OR)
      1.031, 95% CI 1.005-1.058, p = 0.017). In 2007 the residents had been restrained
      longer, and a higher proportion were restrained for unknown reasons. CONCLUSIONS:
      Physical restraint use is still common. Moreover, the findings of this study
      suggest a small increase (OR 1.031) in the prevalence of physical restraint use
      from 2000 to 2007 adjusted for residents' characteristics.

PMID- 22414563
TI  - In vitro genotoxicity of neutral red after photo-activation and metabolic
      activation in the Ames test, the micronucleus test and the comet assay.
AB  - Neutral red (Nr) is relatively non-toxic and is widely used as indicator dye in
      many biological test systems. It absorbs visible light and is known to act as a
      photosensitizer, involving the generation of reactive oxygen species (type-I
      reaction) and singlet oxygen (type-II reaction). The mutagenicity of Nr was
      determined in the Ames test (with Salmonella typhimurium strains TA1535, TA97,
      TA98, TA98NR, TA100, and TA102) with and without metabolic activation, and with
      and without photo-activation on agar plates. Similarly to the situation following
      metabolic activation, photo-mutagenicity of Nr was seen with all Salmonella
      strains tested, albeit with different effects between these strains. To our
      knowledge, Nr is the only photo-mutagen showing such a broad action. Since the
      effects are also observed in strains not known to be responsive to ROS, this
      indicates that ROS production is not the sole mode of action that leads to photo
      genotoxicity. The reactive species produced by irradiation are short-lived as pre
      irradiation of an Nr solution did not produce mutagenic effects when added to the
      bacteria. In addition, mutagenicity in TA98 following irradiation was stronger
      than in the nitroreductase-deficient strain TA98NR, indicating that nitro
      derivatives that are transformed by bacterial nitroreductase to hydroxylamines
      appear to play a role in the photo-mutagenicity of Nr. Photo-genotoxicity of Nr
      was further investigated in the comet assay and micronucleus test in L5178Y
      cells. Concentration-dependent increases in primary DNA damage and in the
      frequency of micronuclei were observed after irradiation.

PMID- 22414564
TI  - Genotoxicity assessment in patients with thalassemia minor.
AB  - Thalassemia is an inherited blood disorder that affects both genders and results
      in reduced synthesis of hemoglobin, and thus causing anemia. Previous studies
      have shown that the severe form of this disease, thalassemia major, is associated
      with genotoxicity. This includes increases in the level of sister chromatid
      exchange (SCEs), chromosomal aberrations (CAs) and micronuclei. In this study, we
      assessed genotoxicity in the lymphocytes of thalassemia minor subjects using
      sister chromatid exchange (SCE) and chromosomal aberration (CA) assays. In
      addition, we investigated the level of oxidative DNA damage by measuring 8
      hydroxy-2'-deoxyguanosine (8OHdG) biomarker in urine samples. Eighteen
      thalassemia minor subjects and eighteen matched normal healthy controls were
      volunteered in the study. In addition, seven thalassemia major patients were
      recruited as positive controls. The results showed increases in the frequency of
      SCEs (P<0.05) in thalassemia minor compared to healthy controls. However, no
      difference in CAs frequency was detected between thalassemia minor and controls
      (P>0.05). Both SECs and CAs in thalassemia major patients were significantly
      higher compared to other groups (P<0.05). Regarding urine 8OHdG levels, the
      result showed a slight increase in thalassemia minor compared to healthy controls
      but the difference was not significant (P>0.05). In conclusion, our results
      showed that thalassemia minor is associated with genotoxicity to blood
      lymphocytes as indicated by SCEs assay.

PMID- 22414565
TI  - Recurrent gastric varices bleeding after living-related liver transplantation
      successfully eradicated by splenic artery embolization.
AB  - Living related liver transplantation (LRLT) may not be the only treatment for
      recurrent bleeding due to severe gastric varices secondary to left-side portal
      hypertension and splenic vein thrombosis. Splenectomy is the preferred long-term
      standard treatment for non-orthotopic liver transplantation patients, but
      additional treatments such as post-transplantation partial splenic arterial
      embolization to preserve the immunological function of the spleen and thus
      prevent the occurrence of post LRLT severe infection are suggested for these
      patients.

PMID- 22414566
TI  - Perspectives for improving the evaluation and access of therapies for rare lung
      diseases in Europe.
AB  - The approach to treating a rare disease is different to that taken for more
      common diseases. Small patient cohorts alter clinical trial design and limit
      enrollment, and the picture for rare lung diseases is further complicated by the
      fact that most are composed of a variety of clinical phenotypes. Since the
      outcome measures of lung impairment have considerable test-to-test variability,
      potential new therapies face a substantial challenge. In this paper we will
      review the current sources of clinical data for rare lung diseases and the
      regulatory challenges encountered by their treatment, with particular reference
      to alpha(1)-antitrypsin deficiency, lymphangioleiomyomatosis, cystic fibrosis,
      and pulmonary alveolar proteinosis. Strategies will also be identified for the
      better utilization of available data from patients with rare lung diseases,
      recognizing that the development cost of new therapies and the number of patients
      who will ultimately use them may not be aligned. Also important is improved
      communication between patients and their organizations, basic researchers,
      clinicians and their registries, drug developers, regulators such as the European
      Medicines Agency, and national health services. At present, licensing and
      reimbursement requirements are not aligned, either nationally or internationally,
      and variations also exist in drug availability between countries because of
      different national licensing and reimbursement rules. The changes needed to
      optimize European rare lung disease therapies include a commitment to develop
      empowered patient communities as advocates for therapy, the development of novel
      trial designs with new endpoints, and for regulatory bodies to be willing to
      accept nontraditional models of efficacy for orphan drugs.

PMID- 22414567
TI  - Risk assessment of development of hepatic decompensation in histologically proven
      hepatitis B viral cirrhosis using liver stiffness measurement.
AB  - BACKGROUND/AIMS: There are few studies regarding the predictive value of liver
      stiffness measurement (LSM) for development of hepatic decompensation. We
      assessed the risk of hepatic decompensations in B-viral compensated cirrhosis,
      using an LSM and LSM-based model (LSM-spleen diameter to platelet ratio score,
      LSPS = LSM * spleen diameter/platelet count) in a prospective, longitudinal
      study. METHODS: We analyzed 217 patients with histologically proven B-viral
      cirrhosis, well-preserved liver function, and no history of decompensation. The
      Kaplan-Meier and Cox regression method were used to examine the major endpoint,
      time to the first decompensation event, defined as development of ascites,
      hepatic encephalopathy, variceal hemorrhage, and deterioration of liver function
      to Child-Pugh class B/C. RESULTS: During follow-up, 26 patients experienced
      hepatic decompensation, ascites (n = 22), hepatic encephalopathy (n = 11),
      variceal hemorrhage (n = 9), and deterioration of liver function (n = 20). For
      risk stratification, patients were grouped as LSM <13, 13-18, and >=18 kPa, and
      from multivariate analysis, patients with LSM 13-18 kPa [hazard ratio (HR) 4.547/
      p = 0.044] and >=18 kPa (HR 12.446/p < 0.001) retained independently higher risks
      than patients with LSM <13 kPa. Similarly, when patients were grouped as LSPS
      <1.1, 1.1-2.5, and >=2.5, those with LSPS 1.1-2.5 (HR 5.796/p = 0.004) and >=2.5
      (HR 13.618/p < 0.001) retained independently higher risks than those with LSPS
      <1.1. CONCLUSION: LSM and LSPS are useful in risk assessment of hepatic
      decompensation among complication-naive B-viral cirrhotic patients.

PMID- 22414568
TI  - Antiretroviral nucleoside analogues suppress antibody synthesis in human B
      lymphocytes.
AB  - BACKGROUND: Some antiretroviral nucleoside reverse transcriptase inhibitors
      (NRTI) impair mitochondrial polymerase-gamma and T-cell proliferation, possibly
      by pyrimidine depletion. We aimed to analyse NRTI effects on the content of
      mitochondrial DNA (mtDNA) and B-cells, and on their proliferation and antibody
      synthesis. METHODS: Peripheral blood B-lymphocytes from six healthy individuals
      were stimulated in vitro with interleukin-4 and Staphylococcus aureus
      superantigen in the presence or absence of NRTI in concentrations equivalent to,
      or fivefold exceeding, human peak plasma levels. We also tested the effects of
      uridine, a pyrimidine precursor, which has antagonized NRTI toxicities in other
      models. RESULTS: During 9 days of culture, B-lymphocyte proliferation and
      vitality were not affected by NRTI. Didanosine and stavudine, but not zidovudine,
      dose-dependently induced mtDNA depletion. All three NRTI significantly and dose
      dependently impaired the synthesis of all immunoglobulin classes. The
      lymphocytotoxic effects of the thymidine analogues zidovudine and stavudine on B
      lymphocytes were antagonized by the addition of uridine. CONCLUSIONS: Didanosine,
      stavudine and zidovudine induce mitochondrial toxicity in human B-lymphocytes and
      impair the immunoglobulin synthesis in vitro, warranting further studies on their
      in vivo effects.

PMID- 22414569
TI  - Rehabilitative management of swallowing and oral-motor movements in patients with
      tetanus of a public service in Brazil.
AB  - When looking at developing countries, the prolonged intensive medical and nursing
      care required by many patients places extra demands on an already stretched
      healthcare budget. The purpose of this study was to verify the effectiveness of a
      systematic rehabilitative program for swallowing and oral-motor movements in
      intensive care unit patients with the diagnosis of tetanus. Forty-five patients
      who were clinically diagnosed with tetanus were included in the study.
      Participants were divided in two groups: GI - consisted of 18 tetanus patients
      who were consecutively admitted to the infectious disease ICU from January 2002
      to December 2005, prior to the existence of a systematic swallowing and oral
      motor intervention; GII - consisted of 27 tetanus patients who were consecutively
      admitted to the infectious disease ICU from January 2006 to December 2009 and
      were submitted to a specific rehabilitative management of swallowing and of the
      oral-motor movements. Results indicate that the proposed rehabilitative program
      reduced by approximately 50% the time patients remained in the ICU. The
      significant improvement observed in patients with tetanus who were submitted to
      the rehabilitative program for swallowing and oral-motor movements occurred in
      conjunction with a reduction in the amount of time necessary to reintroduce oral
      feeding, to decannulate and to remove the feeding tubes. In conclusion,
      swallowing/muscle exercise, in patients with severe/very severe tetanus, seem to
      promote the remission of muscle tension and seem to maximize functional
      swallowing.

PMID- 22414570
TI  - Synergistic effects of antidementia drugs on spatial learning and recall in the
      APP23 transgenic mouse model of Alzheimer's disease.
AB  - Current treatment of Alzheimer's disease rests on cholinergic and anti
      glutamatergic substances. It has been suggested that acetylcholine is required
      for memory acquisition but is less important for memory retrieval. It was our
      goal to investigate the effects of treatment with donepezil, memantine, and a
      combination thereof on spatial memory. We assessed spatial memory of male wild
      type and B6C3-Tg(APPswe,PSEN1dE9)85Dbo (APP23) transgenic animals in a complex
      dry-land maze. Animals were treated with donepezil (1 mg/kg) and memantine (10
      mg/kg). Total time to escape from the maze decreased in 4.5 month old sham
      treated wild-type animals and, to a lesser extent, in APP23 animals. Analysis of
      time spent moving and resting revealed that the treatment effect is conferred by
      a reduction of the moving time for donepezil and a reduction of the resting time
      for memantine. Combination treatment with donepezil and memantine fostered a
      greater improvement than treatment with either substance alone. We conclude that
      enhancement of spatial learning in a dry-land maze on cholinergic or anti
      glutamatergic treatment is differentially conferred during moving of the animals,
      possibly reflecting acquisition of spatial information, and resting of the
      animals, possibly reflecting retrieval of spatial information. Combination
      treatment with donepezil and memantine exerts a synergistic effect improving both
      moving time and resting time and thus possibly both spatial learning and
      retrieval.

PMID- 22414572
TI  - Differential responses of white adipose tissue and brown adipose tissue to
      caloric restriction in rats.
AB  - Caloric restriction (CR) slows the aging process and extends longevity, but the
      exact underlying mechanisms remain debatable. It has recently been suggested that
      the beneficial action of CR may be mediated in part by adipose tissue remodeling.
      Mammals have two types of adipose tissue: white adipose tissue (WAT) and brown
      adipose tissue (BAT). In this study, proteome analysis using two-dimensional gel
      electrophoresis combined with MALDI-TOF MS, and subsequent analyses were
      performed on both WAT and BAT from 9-month-old male rats fed ad libitum or
      subjected to CR for 6 months. Our findings suggest that CR activates
      mitochondrial energy metabolism and fatty acid biosynthesis in WAT. It is likely
      that in CR animals WAT functions as an energy transducer from glucose to energy
      dense lipid. In contrast, in BAT CR either had no effect on, or down-regulated,
      the mitochondrial electron transport chain, but enhanced fatty acid biosynthesis.
      This suggests that in CR animals BAT may change its function from an energy
      consuming system to an energy reservoir system. Based on our findings, we
      conclude that WAT and BAT cooperate to use energy effectively via a differential
      response of mitochondrial function to CR.

PMID- 22414571
TI  - Hippocampal shape analysis in Alzheimer's disease and frontotemporal lobar
      degeneration subtypes.
AB  - Hippocampal pathology is central to Alzheimer's disease (AD) and other forms of
      dementia such as frontotemporal lobar degeneration (FTLD). Autopsy studies have
      shown that certain hippocampal subfields are more vulnerable than others to AD
      and FTLD pathology, in particular the subiculum and cornu ammonis 1 (CA1). We
      conducted shape analysis of hippocampi segmented from structural T1 MRI images on
      clinically diagnosed dementia patients and controls. The subjects included 19 AD
      and 35 FTLD patients [13 frontotemporal dementia (FTD), 13 semantic dementia
      (SD), and 9 progressive nonfluent aphasia (PNFA)] and 21 controls. Compared to
      controls, SD displayed severe atrophy of the whole left hippocampus. PNFA and FTD
      also displayed atrophy on the left side, restricted to the hippocampal head in
      FTD. Finally, AD displayed most atrophy in left hippocampal body with relative
      sparing of the hippocampal head. Consistent with neuropathological studies, most
      atrophic deformation was found in CA1 and subiculum areas in FTLD and AD.

PMID- 22414573
TI  - Start up partial nitrification at low temperature with a real-time control
      strategy based on blower frequency and pH.
AB  - In this study, the performance of partial nitrification via nitrite at low
      temperature was investigated in a pilot-scale sequencing batch reactor (SBR) with
      a working volume of 7.0m(3). A novel real-time control strategy, based on blower
      frequency (BF) and pH, was designed and evaluated. The nitrogen break point (NBP)
      in the BF curve and the nitrate/nitrite apex point (NAP) in the pH curve were
      used to identify the endpoint of the aerobic and anoxic phases, respectively. The
      nitrite accumulation rate (NAR) rapidly increased from 19.8% to 90%. Partial
      nitrification was achieved at low temperature (11-16 degrees C) in 40 days and
      was stably maintained for as long as 140 days by applying a real-time control
      strategy based on pH and BF. Fluorescence in situ hybirdization (FISH) results
      demonstrated that ammonia oxidation bacteria (AOB) had developed into the
      dominant nitrifying bacteria compared to nitrite oxidation bacteria (NOB) in the
      system.

PMID- 22414574
TI  - Effect of increasing anodic NaCl concentration on microbial fuel cell
      performance.
AB  - High salinity effluents represent an estimated 5% of the wastewater generated
      worldwide. In microbial fuel cells, high salinity is usually considered
      beneficial to power production because increased conductivity facilitates proton
      transfer and therefore decreases the internal resistance of the system. However,
      high salt concentrations are known to adversely affect the physiology of
      anaerobic microbial consortia. In this study, the effect of increasing NaCl
      concentration in the anode chamber of a microbial fuel cell fed with sodium
      acetate was tested. Adding up to 20 g L(-1) of NaCl enhanced the overall
      performance of the system, reducing the internal resistance by 33% and increasing
      the maximum power production by 30%. Higher NaCl concentration proved detrimental
      to the system. However, the Coulombic efficiency started to be affected at a much
      lower NaCl concentration of 10 g L(-1), showing that the anodophilic bacteria are
      sensitive to NaCl at relatively low concentrations.

PMID- 22414575
TI  - Enzymatic production of xylooligosaccharides from alkali solubilized xylan of
      natural grass (Sehima nervosum).
AB  - In this study, a process for producing XOS from Sehima nervosum grass was
      developed. The grass contains 28.1% hemicellulose. NaOH and steam application
      yielded 98% of original xylan in contrast to 85% by KOH application. Hydrolysis
      of xylan with commercial xylanase caused breakdown into XOS comprising of
      xylobiose, xylotriose along with xylose. Response surface model (RSM) revealed
      highest xylobiose yield (11 g/100g xylan) at pH 5.03, temperature 45.19 degrees
      C, reaction time 10.11h with enzyme dose 17.41 U. Similarly for maximizing
      xylotriose yield, ideal hydrolysis conditions were pH 5.11, temperature 40.33
      degrees C, reaction time 16.55 h with enzyme dose 13.20 U. A two step process
      encompassing xylan fractionation and enzymatic hydrolysis enabled XOS production
      from the S. nervosum grass.

PMID- 22414576
TI  - Cultivation of a thermo-tolerant microalga in an outdoor photobioreactor:
      influences of CO2 and nitrogen sources on the accelerated growth.
AB  - A photobioreactor was designed to evaluate the performance of a newly isolated
      thermo-tolerant microalga Desmodesmus sp. F2 in municipal wastewater under
      tropical outdoor conditions. The environmental parameters, levels of nutrients,
      and growth rates were monitored during the cultivations to elucidate the factors
      that contributed to accelerated growth after lag phase. Cultures bubbled with
      CO(2)-air had about 20% higher yields than the air-bubbled culture, and 2% of
      CO(2) at a flux rate of 5L/min was sufficient to reach this increased yield. In
      the cultures bubbled with CO(2)-air, the microalgal cells preferentially utilized
      ammonium and nitrate, while the air-bubbled culture made greater use of ammonium
      and organic nitrogen. In conclusion, the factors required for microalga
      Desmodesmus sp. F2 to achieve accelerated growth in tropical outdoor conditions
      include (1) 2% CO(2) bubbling; (2) a level of ammonium higher than 100 MUM; and
      (3) a level of nitrate higher than 400 MUM.

PMID- 22414577
TI  - Potential of jackfruit peel as precursor for activated carbon prepared by
      microwave induced NaOH activation.
AB  - The feasibility of preparing activated carbon (JPAC) from jackfruit peel, an
      industrial residue abundantly available from food manufacturing plants via
      microwave-assisted NaOH activation was explored. The influences of chemical
      impregnation ratio, microwave power and radiation time on the properties of
      activated carbon were investigated. JPAC was examined by pore structural
      analysis, scanning electron microscopy, Fourier transform infrared spectroscopy,
      nitrogen adsorption isotherm, elemental analysis, surface acidity/basicity and
      zeta potential measurements. The adsorptive behavior of JPAC was quantified using
      methylene blue as model dye compound. The best conditions resulted in JPAC with a
      monolayer adsorption capacity of 400.06 mg/g and carbon yield of 80.82%. The
      adsorption data was best fitted to the pseudo-second-order equation, while the
      adsorption mechanism was well described by the intraparticle diffusion model. The
      findings revealed the versatility of jackfruit peels as good precursor for
      preparation of high quality activated carbon.

PMID- 22414578
TI  - MetaPath: an electronic knowledge base for collating, exchanging and analyzing
      case studies of xenobiotic metabolism.
AB  - The MetaPath knowledge base was developed for the purpose of archiving, sharing
      and analyzing experimental data on metabolism, metabolic pathways and crucial
      supporting metadata. The MetaPath system grew out of the need to compile and
      organize the results of metabolism studies into a systematic database to
      facilitate data comparisons and evaluations. Specialized MetaPath data evaluation
      tools facilitate the review of pesticide metabolism data submitted for regulatory
      risk assessments as well as exchange of results of complex analyses used in
      regulation and research. Customized screen editors called Composers were
      developed to automate data entry into MetaPath while also streamlining the
      production of agency specific study summaries such as the Data Evaluation Records
      (DER) used by the US EPA Office of Pesticide Programs. Efforts are underway
      through an Organization for Economic Co-operation and Development (OECD) work
      group to extend the use of DER Composers as harmonized templates for rat
      metabolism, livestock residue, plant residue and environmental degradation
      studies.

PMID- 22414579
TI  - Systems biology of tumor dormancy: linking biology and mathematics on multiple
      scales to improve cancer therapy.
AB  - For many decades, it has been appreciated that tumor progression is not
      monotonic, and development of a cancer cell does not equate to inevitable cancer
      presentation in the clinic. Tumor progression is challenged by numerous intrinsic
      and extrinsic bottlenecks that can hold the tumor in dormant stages for prolonged
      periods. Given the complex, multiscale nature of these bottlenecks, the Center of
      Cancer Systems Biology organized a workshop on critical issues of systems biology
      of tumor dormancy. The program for the meeting this past July, chaired by N.
      Almog and H. Enderling, included discussions and interactive breakout sessions on
      regulation of tumor dormancy by angiogenesis, tumor-immune system interactions,
      cancer stem cell kinetics, and cell signaling pathways. Three important
      conclusions emerged from the meeting. The first was the urgent need to
      differentiate between tumor cell and tumor population dormancy of the primary
      tumor and metastatic deposits, the second was the continued need for
      interdisciplinary dialogs, and the third was the need to bring cross-scale
      mechanistic thinking to the field to achieve a more robust understanding of tumor
      dormancy and its clinical implications.

PMID- 22414580
TI  - Proteomic portrait of human breast cancer progression identifies novel prognostic
      markers.
AB  - Breast cancer is the second leading cause of cancer death for women in the United
      States. Of the different subtypes, estrogen receptor-negative (ER(-)) tumors,
      which are ErbB2+ or triple-negative, carry a relatively poor prognosis. In this
      study, we used system-wide analysis of breast cancer proteomes to identify
      proteins that are associated with the progression of ER(-) tumors. Our two-step
      approach included an initial deep analysis of cultured cells that were obtained
      from tumors of defined breast cancer stages, followed by a validation set using
      human breast tumors. Using high-resolution mass spectrometry and quantification
      by Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC), we
      identified 8,750 proteins and quantified 7,800 of them. A stage-specific
      signature was extracted and validated by mass spectrometry and
      immunohistochemistry on tissue microarrays. Overall, the proteomics signature
      reflected both a global loss of tissue architecture and a number of metabolic
      changes in the transformed cells. Proteomic analysis also identified high levels
      of IDH2 and CRABP2 and low levels of SEC14L2 to be prognostic markers for overall
      breast cancer survival. Together, our findings suggest that global proteomic
      analysis provides information about the protein changes specific to ER(-) breast
      tumor progression as well as important prognostic information.

PMID- 22414581
TI  - Tumor microenvironment complexity: emerging roles in cancer therapy.
AB  - The tumor microenvironment (TME) consists of cells, soluble factors, signaling
      molecules, extracellular matrix, and mechanical cues that can promote neoplastic
      transformation, support tumor growth and invasion, protect the tumor from host
      immunity, foster therapeutic resistance, and provide niches for dormant
      metastases to thrive. An American Association for Cancer Research (AACR) special
      conference held on November 3-6, 2011, addressed five emerging concepts in our
      understanding of the TME: its dynamic evolution, how it is educated by tumor
      cells, pathways of communication between stromal and tumor cells,
      immunomodulatory roles of the lymphatic system, and contribution of the
      intestinal microbiota. These discussions raised critical questions on how to
      include the analysis of the TME in personalized cancer diagnosis and treatment.

PMID- 22414582
TI  - Perceptions of heart disease in community-dwelling Lebanese.
AB  - BACKGROUND: People's beliefs about heart disease affect how quickly they respond
      to a cardiac event and their subsequent recovery. AIMS: To explore beliefs about
      symptoms, causes, timeline, consequences and curability of heart disease in
      Lebanese adults; and to identify differences in these beliefs by demographic
      characteristics and cardiovascular risk status. METHODS: A total of 401 visitors
      of patients admitted to two hospitals in Beirut were interviewed using the
      modified Illness Perception Questionnaire, in addition to demographic and health
      related questions. Participants were 25 years and older, visiting patients
      hospitalised for 7 days or less and had no history of coronary artery disease
      (CAD). RESULTS: Participants were mostly young (56.2% < 40 years of age), married
      (61.3%), women (57.9%), with at least secondary education (69%). The majority of
      participants perceived heart disease to be a chronic illness, with serious
      consequences. Eighty per cent identified the most common symptoms and causes of
      CAD. Over 80% believed that CAD can be controlled by lifestyle but 57.67% doubted
      complete recovery from a heart attack. Younger, single individuals and those with
      higher socioeconomic status perceived significantly stronger control than older,
      married and lower socioeconomic status participants. Smokers and diabetics
      perceived lower control over CAD than their counterparts. Participants with
      family history of CAD considered it more chronic than those without history.
      CONCLUSION: The findings reflect knowledge of symptoms and causes of CAD, but
      inconsistent beliefs about its control. Educational campaigns are needed to
      dispel misconceptions.

PMID- 22414583
TI  - Patients with a congenital heart defect and type D personality feel functionally
      more impaired, report a poorer health status and quality of life, but use less
      healthcare.
AB  - BACKGROUND: Type D personality, characterized by high levels of negative
      affectivity and social inhibition, is related to mortality, morbidity, poor
      health status, quality of life (QoL) and less healthcare utilization in various
      cardiovascular patient groups. To date, studies in patients with congenital heart
      disease (CHD) are lacking. AIMS: (1) To examine the prevalence of type D
      personality in CHD patients; (2) to compare type D to non-type D patients with
      regard to disease severity, functional status, health status and QoL; and (3) to
      examine the extent to which type D personality is independently related to
      healthcare utilization. METHODS: A total of 1109 adult CHD patients were included
      in a questionnaire survey. Due to missing data, 302 patients were excluded.
      RESULTS: The prevalence of Type D personality was 20.4%. Type D patients reported
      a poorer functional status, health status and QoL than non-type D patients
      (p<0.05). Type D patients reported less healthcare use than non-type D patients
      (primary and cardiac outpatient healthcare: adjusted OR=0.56, 95% CI=0.35-0.90;
      inpatient healthcare: adjusted OR=0.38, 95% CI=0.17-0.83). Results of a post-hoc
      analysis showed a high prevalence of type D personality in patients with a poor
      functional status who did not consult their cardiologist. CONCLUSION: type D
      patients report a poorer functional status, health status and QoL, but less
      healthcare utilization. In clinical practice, patients should be screened for
      type D personality, since social inhibition may prevent them from contacting a
      healthcare provider in the event of symptom aggravation.

PMID- 22414585
TI  - A 21st century evaluation of the safety of oral vitamin D.
AB  - The safety of daily consumption of vitamin D was examined. A detailed literature
      search was conducted using the search term vitamin D; primary and secondary
      sources of original data and meta-analyses and systematic reviews were evaluated
      and summarized. A large body of scientific evidence demonstrates that long-term
      daily intakes of 600 to 800 IU of vitamin D are insufficient to achieve and
      sustain vitamin D adequacy (serum 25-hydroxyergocalciferol + 25
      hydroxycholecalciferol concentration >75 nmol/L). Maximization of the physiologic
      benefits of vitamin D to the musculoskeletal system, the central and peripheral
      nervous systems, the heart and central and peripheral cardiovascular systems, the
      respiratory system, the skin, the eyes, dentition, glucoregulation,
      immunoregulation, and disease resistance requires daily vitamin D intakes of at
      least 1500 IU. Because long-term daily intakes up to and including 10 000 IU of
      vitamin D do not produce signs or symptoms of vitamin D toxicity and are safe for
      the entire general population of otherwise healthy adults, even daily vitamin D
      intakes of 2000 IU allow for the often-cited and excessively conservative five
      fold safety factor. In conclusion, long-term daily intakes of up to and including
      10 000 IU of vitamin D maximize physiologic benefits and are safe.

PMID- 22414586
TI  - A new polemic to acrylamide toxicity.

PMID- 22414584
TI  - Commonalities and differences in correlates of depressive symptoms in men and
      women with heart failure.
AB  - OBJECTIVE: (i) To compare the prevalence and severity of depressive symptoms
      between men and women enrolled in a large heart failure (HF) registry. (ii) To
      determine gender differences in predictors of depressive symptoms from
      demographic, behavioral, clinical, and psychosocial factors in HF patients.
      METHODS: In 622 HF patients (70% male, 61 +/- 13 years, 59% NYHA class III/IV),
      depressive symptoms were assessed by the Patient Health Questionnaire (PHQ-9).
      Potential correlates were age, ethnicity, education, marital and financial
      status, smoking, exercise, body mass index (BMI), HF etiology, NYHA class,
      comorbidities, functional capacity, anxiety, and perceived control. To identify
      gender-specific correlates of depressive symptoms, separate logistic regression
      models were built by gender. RESULTS: Correlates of depressive symptoms in men
      were financial status (p = 0.027), NYHA (p = 0.001); functional capacity (p <
      0.001); health perception (p = 0.043); perceived control (p = 0.002) and anxiety
      (p < 0.001). Correlates of depressive symptoms in women were BMI (p = 0.003);
      perceived control (p = 0.013) and anxiety (p < 0.001). CONCLUSIONS: In HF
      patients, lowering depressive symptoms may require gender-specific interventions
      focusing on weight management in women and improving perceived functional
      capacity in men. Both men and women with HF may benefit from anxiety reduction
      and increased control.

PMID- 22414587
TI  - Potato fiber protects the small intestinal wall against the toxic influence of
      acrylamide.
AB  - OBJECTIVE: Acrylamide is a neurotoxic, genotoxic substance present in many
      commonly consumed food products and has been shown to have carcinogenic effects
      in rodents. The protective effects (if any) of potato fiber preparations,
      composed of cell wall material from potatoes, against the toxic influence of
      dietary acrylamide on the small intestinal wall were investigated. METHODS: Male
      mice of the BALB/c strain were used in the study. Acrylamide was administered to
      the mice in their drinking water (0.5 mg/kg of body weight per day) and one of
      two types of potato fiber preparations (heated or raw potato fiber preparation)
      was added to their feed (2% addition to their feed). Histomorphometry of the
      small intestinal wall, hemoglobin adducts of acrylamide, animal weight, and feed
      and water consumption analyses were performed. RESULTS: Acrylamide altered the
      morphology and histology of the small intestinal wall, decreasing proliferation,
      myenteron and submucosal thicknesses, villus length, fractal dimension, crypt
      depth, crypt number, and the small intestinal absorptive surface. Conversely,
      apoptosis, hemoglobin adduct levels, intensity of epithelium staining, enterocyte
      number, villus epithelial thickness, and crypt width and parameters associated
      with nerve ganglia were increased. The two potato fiber preparations that were
      used abolished the negative influences of acrylamide on the small intestinal wall
      and had no influence on the hemoglobin adduct levels of acrylamide. CONCLUSION:
      The negative impact of acrylamide on the histologic structure, regeneration, and
      innervation of the small intestinal wall and the absorptive function of the small
      intestinal mucosa can be abolished by dietary potato fiber preparations.

PMID- 22414589
TI  - Labial melanotic macule: a potential pitfall on reflectance confocal microscopy.

PMID- 22414588
TI  - Effects of a reduced dose of stavudine on the incidence and severity of
      peripheral neuropathy in HIV-infected adults in South Africa.
AB  - BACKGROUND: Although recent World Health Organization (WHO) guidelines recommend
      withdrawing stavudine (d4T) from first-line antiretroviral therapy (ART), it
      remains commonly used in resource-limited settings. In 2006, WHO recommended
      decreasing the dose of d4T from 40 mg to 30 mg to mitigate toxicities. We
      compared the incidence and severity of peripheral neuropathy by d4T dose in a
      retrospective cohort study. METHODS: Patients' charts from an ART-naive
      population at a rural clinic in KwaZulu-Natal, South Africa, were retrospectively
      reviewed for signs and symptoms of incident peripheral neuropathy and were graded
      for severity using the DAIDS scale. Patients enrolled prior to the WHO guideline
      change were included in the study if they were on d4T 40 mg for >=6 months. After
      the guideline change all patients were initiated on d4T 30 mg. RESULTS: A total
      of 475 patients were analysed, including 235 in the 40 mg cohort (152.7 person
      years [py]) and 240 in the 30 mg cohort (244.7 py). Incidence of peripheral
      neuropathy was 90.4/100 py (95% CI 75.9, 106.8) in the 40 mg cohort versus
      40.5/100 py (95% CI 32.9, 49.3) in the 30 mg group (incidence rate ratio 0.45;
      P<0.0001). There was no difference in proportion of severe peripheral neuropathy
      cases (grade 3/4) between the cohorts: 8.3% in the 40 mg group and 8.9% in the 30
      mg group (P=1.0). In a multivariate analysis, risk of peripheral neuropathy was
      associated with increasing age (hazard ratio [HR] 1.65, 95% CI 1.24, 2.19), 40 mg
      dose (HR 2.1, 95% CI 1.61, 2.74) and concurrent tuberculosis therapy (HR 1.41,
      95% CI 1.06, 1.87). CONCLUSIONS: Incidence of peripheral neuropathy in the 40 mg
      cohort was extremely high and, although lower, the rate in the 30 mg cohort was
      nonetheless unacceptably high.

PMID- 22414590
TI  - The origin of the audiovisual bounce inducing effect: a TMS study.
AB  - The audiovisual bounce inducing effect (ABE) is a bouncing percept induced by the
      presence of a sound at the moment of two moving objects intercepting in a motion
      display otherwise perceived as streaming. The origin of the ABE is still debated:
      the effect could arise from the subtraction of attentional resources caused by
      the sound (needed to favor the perception of streaming), and/or from the cross
      modal integration (binding) of visual and auditory information: indeed bouncing
      like sounds are best in inducing the ABE. The neural mechanism responsible for
      the ABE is still unknown. Here, by using offline TMS, we investigated the role of
      the posterior parietal cortex (PPC), thought to be involved in both attentional
      and binding processes, in the generation of the ABE. Results show that disrupting
      the functional integrity of the right (but not the left) PPC has the effect of
      weakening the binding of cross-modal information, which reduces the magnitude of
      the ABE. Indeed, if the effect of parietal stimulation was merely to disrupt
      attention, we would expect an increase (not a decrease) of bouncing percepts. The
      present study not only shows the involvement of the right PPC in the ABE, but
      also support the notion that cross-modal binding (and not attention) is at the
      origin of the ABE.

PMID- 22414591
TI  - Tracking of pitch probabilities in congenital amusia.
AB  - Auditory perception involves not only hearing a series of sounds but also making
      predictions about future ones. For typical listeners, these predictions are
      formed on the basis of long-term schematic knowledge, gained over a lifetime of
      exposure to the auditory environment. Individuals with a developmental disorder
      known as congenital amusia show marked difficulties with music perception and
      production. The current study investigated whether these difficulties can be
      explained, either by a failure to internalise the statistical regularities
      present in music, or by a failure to consciously access this information. Two
      versions of a melodic priming paradigm were used to probe participants' abilities
      to form melodic pitch expectations, in an implicit and an explicit manner. In the
      implicit version (Experiment 1), participants made speeded, forced-choice
      discriminations concerning the timbre of a cued target note. In the explicit
      version (Experiment 2), participants used a 1-7 rating scale to indicate the
      degree to which the pitch of the cued target note was expected or unexpected.
      Target notes were chosen to have high or low probability in the context of the
      melody, based on the predictions of a computational model of melodic expectation.
      Analysis of the data from the implicit task revealed a melodic priming effect in
      both amusic and control participants whereby both groups showed faster responses
      to high probability than low probability notes rendered in the same timbre as the
      context. However, analysis of the data from the explicit task revealed that
      amusic participants were significantly worse than controls at using explicit
      ratings to differentiate between high and low probability events in a melodic
      context. Taken together, findings from the current study make an important
      contribution in demonstrating that amusic individuals track melodic pitch
      probabilities at an implicit level despite an impairment, relative to controls,
      when required to make explicit judgments in this regard. However the unexpected
      finding that amusics nevertheless are able to use explicit ratings to distinguish
      between high and low probability notes (albeit not as well as controls) makes a
      similarly important contribution in revealing a sensitivity to musical structure
      that has not previously been demonstrated in these individuals.

PMID- 22414592
TI  - The role of inferior frontal gyrus in processing Chinese classifiers.
AB  - The Chinese classifier system classifies nouns and builds a relation between
      classifiers and their corresponding nouns. This functional magnetic resonance
      imaging (fMRI) study examined brain activation of Chinese classifiers during
      reading comprehension. Thirty-four participants read and performed semantic
      congruency judgments on congruent, inside-classifier (IC) violated, and outside
      classifier (OC) violated sentences. The IC and OC violations were created by
      changing the correct classifier to an inappropriate classifier and a non
      classifier, respectively. The comparison of the IC violation vs. the congruent
      condition produced greater activation in the mid-ventral region (BA 45) of the
      left inferior frontal gyrus (IFG), suggesting an increased demand on semantic
      processing. Contrasting different subtypes of IC violation produced greater
      activation in the right IFG (BAs 45 and 47), indicating that processing
      mass/count classifiers involves distinct brain activations. The OC violation
      produced greater activation in the left IFG (BAs 45 and 44), suggesting both
      semantic and syntactic processing. These results indicate that different parts of
      the IFG contribute to syntactic and semantic processing of classifier phrases in
      reading Chinese for comprehension.

PMID- 22414593
TI  - Social economic decision-making across the lifespan: An fMRI investigation.
AB  - Recent research in neuroeconomics suggests that social economic decision-making
      may be best understood as a dual-systems process, integrating the influence of
      deliberative and affective subsystems. However, most of this research has focused
      on young adults and it remains unclear whether our current models extend to
      healthy aging. To address this question, we investigated the behavioral and
      neural basis of simple economic decisions in 18 young and 20 older healthy
      adults. Participants made decisions which involved accepting or rejecting
      monetary offers from human and non-human (computer) partners in an Ultimatum
      Game, while undergoing functional magnetic resonance imaging (fMRI). The
      partners' proposals involved splitting an amount of money between the two
      players, and ranged from $1 to $5 (from a $10 pot). Relative to young adults,
      older participants expected more equitable offers and rejected moderately unfair
      offers ($3) to a larger extent. Imaging results revealed that, relative to young
      participants, older adults had higher activations in the left dorsolateral
      prefrontal cortex (DLPFC) when receiving unfair offers ($1-$3). Age group
      moderated the relationship between left DLPFC activation and acceptance rates of
      unfair offers. In contrast, older adults showed lower activation of bilateral
      anterior insula in response to unfair offers. No age group difference was
      observed when participants received fair ($5) offers. These findings suggest that
      healthy aging may be associated with a stronger reliance on computational areas
      subserving goal maintenance and rule shifting (DLPFC) during interactive economic
      decision-making. Consistent with a well-documented "positivity effect", older age
      may also decrease recruitment of areas involved in emotion processing and
      integration (anterior insula) in the face of social norm violation.

PMID- 22414594
TI  - Disinhibited feedback as a cause of synesthesia: evidence from a functional
      connectivity study on auditory-visual synesthetes.
AB  - In synesthesia, certain stimuli to one sensory modality lead to sensory
      perception in another unstimulated modality. In addition to other models, a two
      stage model is discussed to explain this phenomenon, which combines two
      previously formulated hypotheses regarding synesthesia: direct cross-activation
      and hyperbinding. The direct cross-activation model postulates that direct
      connections between sensory-specific areas are responsible for co-activation and
      synesthetic perception. The hyperbinding hypothesis suggests that the inducing
      stimulus and the synesthetic sensation are coupled by a sensory nexus area, which
      may be located in the parietal cortex. This latter hypothesis is compatible with
      the disinhibited feedback model, which suggests unusual feedback from multimodal
      convergence areas as the cause of synesthesia. In this study, the relevance of
      these models was tested in a group (n=14) of auditory-visual synesthetes by
      performing a functional connectivity analysis on functional magnetic resonance
      imaging (fMRI) data. Different simple and complex sounds were used as stimuli,
      and functionally defined seed areas in the bilateral auditory cortex (AC) and the
      left inferior parietal cortex (IPC) were used for the connectivity calculations.
      We found no differences in the connectivity of the AC and the visual areas
      between synesthetes and controls. The main finding of the study was stronger
      connectivity of the left IPC with the left primary auditory and right primary
      visual cortex in the group of auditory-visual synesthetes. The results support
      the model of disinhibited feedback as a cause of synesthetic perception but do
      not suggest direct cross-activation.

PMID- 22414595
TI  - The sound of music: differentiating musicians using a fast, musical multi-feature
      mismatch negativity paradigm.
AB  - Musicians' skills in auditory processing depend highly on instrument, performance
      practice, and on level of expertise. Yet, it is not known though whether the
      style/genre of music might shape auditory processing in the brains of musicians.
      Here, we aimed at tackling the role of musical style/genre on modulating neural
      and behavioral responses to changes in musical features. Using a novel, fast and
      musical sounding multi-feature paradigm, we measured the mismatch negativity
      (MMN), a pre-attentive brain response, to six types of musical feature change in
      musicians playing three distinct styles of music (classical, jazz, rock/pop) and
      in non-musicians. Jazz and classical musicians scored higher in the musical
      aptitude test than band musicians and non-musicians, especially with regards to
      tonal abilities. These results were extended by the MMN findings: jazz musicians
      had larger MMN-amplitude than all other experimental groups across the six
      different sound features, indicating a greater overall sensitivity to auditory
      outliers. In particular, we found enhanced processing of pith and sliding up to
      pitches in jazz musicians only. Furthermore, we observed a more frontal MMN to
      pitch and location compared to the other deviants in jazz musicians and left
      lateralization of the MMN to timbre in classical musicians. These findings
      indicate that the characteristics of the style/genre of music played by musicians
      influence their perceptual skills and the brain processing of sound features
      embedded in a musical context. Musicians' brain is hence shaped by the type of
      training, musical style/genre, and listening experiences.

PMID- 22414596
TI  - Prevalence and correlates of suicidal thought and self-destructive behavior among
      an elderly hospital population in Iran.
AB  - BACKGROUND: Few studies have examined suicidal ideation and behavior in
      hospitalized physically ill elderly patients, a group potentially at high risk.
      Our aim was to investigate the prevalence and risk factors for suicide ideation,
      and direct and indirect self-destructive behaviors among a sample of elderly
      inpatients. METHODS: A cross-sectional study was conducted in 2009; 650
      inpatients aged 60 years and over were screened from various medical services in
      teaching hospitals affiliated to Shiraz University of Medical Sciences in Iran.
      Suicidal ideation and behavior were measured with the Beck Scale for Suicidal
      Ideation (BSSI) and the Harmful Behavior Scale (HBS). Depression was measured
      with the Geriatric Depression Scale (GDS), medical burden with the geriatric
      version of the Cumulative Illness Rating Scale (CIRS-G), life events with the
      Paykel Life Event Scale, and social support with the Perceived Social Support
      Scale. RESULT: Of the 650 patients screened with a mean age of 70.5 years (SD +/-
      7.5), 570 met inclusion criteria and of these 123 (21.6%) reported suicidal
      ideation on the BSSI and 80 (14.4%) had at least one self-destructive behavior
      included in the HBS. There was a significant correlation between suicide ideation
      and harmful behaviors (r = 0.503, p = 0.001). In a regression analysis,
      depressive symptoms, increased burden of medical conditions, marital status,
      history of substance use, history of traumatic life events, lack of perceived
      social support, and poor education were associated with both suicide ideation and
      harmful behavior. From demographic variables, living without a spouse and
      unemployment were predictors of suicidal ideation and behavior. CONCLUSION:
      Hospitalized, physically ill elderly patients have high rates of suicidal
      ideation and self-destructive behavior and these vary according to psychosocial
      and clinical factors. The general hospital is therefore a potential site for the
      recognition of suicidal individuals and implementation of proximal suicide
      prevention strategies.

PMID- 22414597
TI  - Implication of new atherosclerotic carotid plaques in the cardiovascular outcome
      of patients with rheumatoid arthritis.

PMID- 22414598
TI  - Cancer of unknown primary site.
AB  - Cancer of unknown primary site (CUP) is a well recognised clinical disorder,
      accounting for 3-5% of all malignant epithelial tumours. CUP is clinically
      characterised as an aggressive disease with early dissemination. Diagnostic
      approaches to identify the primary site include detailed histopathological
      examination with specific immunohistochemistry and radiological assessment. Gene
      profiling microarray diagnosis has high sensitivity, but further prospective
      study is necessary to establish whether patients' outcomes are improved by its
      clinical use. Metastatic adenocarcinoma is the most common CUP histopathology
      (80%). CUP patients are divided into subsets of favourable (20%) and unfavourable
      (80%) prognosis. Favourable subsets are mostly given locoregional treatment or
      systemic platinum-based chemotherapy. Responses and survival are similar to those
      of patients with relevant known primary tumours. Patients in unfavourable subsets
      are treated with empirical chemotherapy based on combination regimens of platinum
      or taxane, but responses and survival are generally poor.

PMID- 22414599
TI  - Retinoblastoma.
AB  - Retinoblastoma is an aggressive eye cancer of infancy and childhood. Survival and
      the chance of saving vision depend on severity of disease at presentation.
      Retinoblastoma was the first tumour to draw attention to the genetic aetiology of
      cancer. Despite good understanding of its aetiology, mortality from
      retinoblastoma is about 70% in countries of low and middle income, where most
      affected children live. Poor public and medical awareness, and an absence of
      rigorous clinical trials to assess innovative treatments impede progress.
      Worldwide, most of the estimated 9000 newly diagnosed patients every year will
      die. However, global digital communications present opportunities to optimise
      standards of care for children and families affected by this rare and often
      devastating cancer. Parents are now leading the effort for widespread awareness
      of the danger of leucocoria. Genome-level technologies could make genetic testing
      a reality for every family affected by retinoblastoma. Best-practice guidelines,
      online sharing of pathological images, point-of-care data entry,
      multidisciplinary research, and clinical trials can reduce mortality. Most
      importantly, active participation of survivors and families will ensure that the
      whole wellbeing of the child is prioritised in any treatment plan.

PMID- 22414600
TI  - Early repolarization ECG pattern in patients with ARVC: normal variant?

PMID- 22414602
TI  - MicroRNA 96 is a post-transcriptional suppressor of anaplastic lymphoma kinase
      expression.
AB  - Anaplastic lymphoma kinase (ALK) constitutes a part of the oncogenic fusion
      proteins nucleophosmin-ALK and echinoderm microtubule-associated protein like 4
      ALK, which are aberrantly expressed in a subset of T-cell anaplastic large-cell
      lymphoma and non-small-cell lung cancer, respectively. The expression of mutated,
      constitutively active ALK also occurs in a subset of neuroblastoma tumors. ALK is
      believed to play an important role in promoting tumor survival. Nevertheless, the
      mechanisms underlying the expression of ALK in cancer cells are not completely
      known. MicroRNA (miR) has been implicated in the regulation of the expression of
      both oncogenes and tumor suppressor genes. We tested the hypothesis that the
      expression of ALK could be regulated by miR. Three Internet-based algorithms
      identified miR-96 to potentially bind with the ALK 3'-untranslated region.
      Notably, miR-96 levels were markedly decreased in ALK-expressing cancer cell
      lines and primary human tumors compared with their normal cellular and tissue
      counterparts. Transfection of the cell lines with miR-96 decreased levels of the
      different forms of ALK protein, without significant effects on ALK mRNA.
      Furthermore, miR-96 decreased the phosphorylation of ALK target proteins,
      including Akt, STAT3, JNK, and type I insulin-like growth factor receptor, and it
      down-regulated JunB. These effects were associated with reduced proliferation,
      colony formation, and migration of ALK-expressing cancer cells. These data
      provide novel evidence that decreases in miR-96 could represent a mechanism
      underlying the aberrant expression of ALK in cancer cells.

PMID- 22414603
TI  - Albendazole causes stage-dependent developmental toxicity and is deactivated by a
      mammalian metabolization system in a modified zebrafish embryotoxicity test.
AB  - The zebrafish embryotoxicity test has previously been combined with an external
      metabolic activation system (MAS) to assess developmental toxicity of metabolites
      produced by maternal metabolism. Due to toxicity of MAS the exposure was limited
      to one early and short period. We have modified the method and included
      additional testing time points with extended exposure durations. Using the
      anthelmintic drug albendazole as a model substance, we demonstrated stage
      dependent toxic effects at three windows of zebrafish embryo development, i.e. 2
      3, 12-14 and 24-28h post fertilization, and showed that MAS, by metabolic
      deactivation, reduced the toxicity of albendazole at all time points. Chemical
      analysis confirmed that albendazole was efficiently metabolized by MAS to the
      corresponding sulfoxide and sulfone, which are non-toxic to zebrafish embryos. To
      conclude, the modified zebrafish embryotoxicity test with MAS can be expanded for
      assessment of metabolites at different developmental stages.

PMID- 22414605
TI  - Chronic disease epidemiology, cancer and mobile global approaches to disease
      prevention.
AB  - The focus of this symposium was worldwide prevention of chronic disease through
      the use of inexpensive Internet pathways, as demonstrated with the Supercourse
      project, and other initiatives, including promoting mobile phone technology (m
      health). This symposium highlighted the need to use the Supercourse to prevent
      cancer and other chronic diseases. It also highlighted several components of the
      Supercourse library, including the former Soviet Union network, the Latin
      American network, and some other initiatives.

PMID- 22414604
TI  - Perfluorooctanoic acid effects on ovaries mediate its inhibition of peripubertal
      mammary gland development in Balb/c and C57Bl/6 mice.
AB  - Exposure to perfluorooctanoic acid (PFOA), a synthetic perfluorinated compound
      and an agonist of peroxisome proliferator-activated receptor alpha (PPARalpha),
      causes stunted mouse mammary gland development in various developmental stages.
      However, the underlying mechanisms remain poorly understood. We found that
      peripubertal PFOA exposure significantly inhibited mammary gland growth in both
      Balb/c and C57Bl/6 wild type mice, but not in C57Bl/6 PPARalpha knockout mice,
      and Balb/c mice were more sensitive to PFOA inhibition. PFOA caused (1) delayed
      or absence of vaginal opening and lack of estrous cycling during the experimental
      period; (2) decreases in ovarian steroid hormonal synthetic enzyme levels; and
      (3) reduced expression of estrogen- or progesterone-induced mammary growth
      factors. Supplementation with exogenous estrogen and/or progesterone reversed the
      PFOA inhibitory effect on mammary gland. These results indicate that PFOA effects
      on ovaries mediate its inhibition of mammary gland development in Balb/c and
      C57Bl/6 mice and that PPARalpha expression is a contributing factor.

PMID- 22414606
TI  - Linkage of data in the study of ethnic inequalities and inequities in health
      outcomes in Scotland, New Zealand and The Netherlands: insights for global study
      of ethnicity and health.
AB  - Reducing inequalities in health is a global priority. An essential tool in
      achieving this reduction is the ability to provide valid measurements of
      inequalities, which are comparable over time and ultimately across countries and
      continents. With valid data a true understanding of inequalities can be
      ascertained, which can begin to inform effective legislation and policy. In this
      workshop, the speakers described in three different countries, Scotland, New
      Zealand and The Netherlands, how record linkage has been used to link ethnic
      status to health and health care measures and so to determine ethnic inequalities
      in health with the ultimate aim of reducing these inequalities.

PMID- 22414607
TI  - Organising a World Congress of Epidemiology (WCE): reflections and lessons from
      the XIX WCE, Scotland.
AB  - The 3-yearly World Congress of Epidemiology is the premier, international,
      scientific conference organised under the auspices of the International
      Epidemiological Association (in open competition). This paper explores the
      justification for seeking to host the Congress and reflects on the structures and
      processes adopted in making the XIXth Congress in Scotland happen. Preparing the
      bid was invaluable for forming collaborations, generating scientific ideas, and
      garnering opinion. After the bid was accepted, we formed a local organising
      committee, named the Management Executive Committee to signal its decision making
      authority; and scientific, fundraising, marketing, international and social
      subcommittees. There was uncertainty about critical matters such as delegate
      numbers, costs and the total budget. Early decisions had to be made on, for
      example, the fee and fundraising target (L250,000), despite financial risks.
      Development of the scientific programme was a critical step that underpinned
      fundraising and marketing and permitted involvement of the international
      committee. Overall the 2011 WCE succeeded. The key ingredients to success were: a
      large collaboration of institutions and individuals; early pledges of financial
      support mostly from the UK; the valuable and relevant experience of the
      professional conference organisers; unstinting support and advice from IEA; and
      the effectiveness of the committee structure. The educational and professional
      development benefits of this WCE will reach a worldwide community and not just
      delegates, because of video, PowerPoint and textual accounts being open access on
      the Internet. This reach is unprecedented for IEA's World Congresses. We
      anticipate that the Congress will translate into better public health practice,
      better future Congresses, advances in epidemiology and improved population
      health.

PMID- 22414609
TI  - Implementation of formalin-fixed, paraffin-embedded cell line pellets as high
      quality process controls in quality assessment programs for KRAS mutation
      analysis.
AB  - In recent years, the mutational status of the KRAS oncogene has become
      incorporated into standard medical care as a predictive marker for therapeutic
      decisions related to patients with metastasized colorectal cancer. This is
      necessary, because these patients benefit from epidermal growth factor receptor
      (EGFR)-targeted therapy with increased progression-free survival only if the
      tumor does not carry a mutation in KRAS. Many different analytical platforms,
      both those commercially available and those developed in house, have been used
      within pathology laboratories to assess KRAS mutational status. For a testing
      laboratory to become accredited to perform such tests, it is essential that they
      perform reliability testing, but it has not previously been possible to perform
      this kind of testing on the complete workflow on a large scale without
      compromising reproducibility or the mimicry of the control sample. We assessed a
      novel synthetic control for formalin-fixed, paraffin-embedded (FFPE) tumor
      samples in a blind study conducted within nine laboratories across Europe. We
      show that FFPE material can, at least in part, mimic clinical samples and we
      demonstrate this control to be a valuable tool in the assessment of platforms
      used in testing for KRAS mutational status.

PMID- 22414608
TI  - The development of neural correlates for memory formation.
AB  - A growing body of literature considers the development of episodic memory systems
      in the brain; the majority are neuroimaging studies conducted during memory
      encoding in order to explore developmental trajectories in memory formation. This
      review considers evidence from behavioral studies of memory development, neural
      correlates of memory formation in adults, and structural brain development, all
      of which form the foundation of a developmental cognitive neuroscience approach
      to memory development. I then aim to integrate the current evidence from
      developmental functional neuroimaging studies of memory formation with respect to
      three hypotheses. First, memory development reflects the development in the use
      of memory strategies, linked to prefrontal cortex. Second, developmental effects
      within the medial temporal lobes are more complex, and correspond to current
      notions about the nature in which the MTL support the formation of memory. Third,
      neurocognitive changes in content representation influence memory. Open issues
      and current directions are discussed.

PMID- 22414610
TI  - Genital prolapse in women.
AB  - INTRODUCTION: Prolapse of the uterus or vagina is usually the result of loss of
      pelvic support, and causes mainly non-specific symptoms. It may affect over half
      of women aged 50 to 59 years, but spontaneous regression may occur. Risks of
      genital prolapse increase with advancing parity and age, increasing weight of the
      largest baby delivered, and hysterectomy. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical questions: What are
      the effects of non-surgical treatments in women with genital prolapse? What are
      the effects of surgical treatments in women with anterior vaginal wall prolapse?
      What are the effects of surgical treatments in women with posterior vaginal wall
      prolapse? What are the effects of surgical treatments in women with upper vaginal
      wall prolapse? What are the effects of using different surgical materials in
      women with genital prolapse? We searched: Medline, Embase, The Cochrane Library,
      and other important databases up to August 2011 (Clinical Evidence reviews are
      updated periodically; please check our website for the most up-to-date version of
      this review). We included harms alerts from relevant organisations such as the US
      Food and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 15 systematic reviews, RCTs, or
      observational studies that met our inclusion criteria. We performed a GRADE
      evaluation of the quality of evidence for interventions. CONCLUSIONS: In this
      systematic review, we present information relating to the effectiveness and
      safety of the following interventions: abdominal Burch colposuspension; abdominal
      sacral colpopexy; abdominal sacrohysteropexy; anterior colporrhaphy with mesh
      reinforcement; laparoscopic surgery; mesh or synthetic grafts; native
      (autologous) tissue; open abdominal surgery; pelvic floor muscle exercises;
      posterior colporrhaphy (with or without mesh reinforcement); posterior
      intravaginal slingplasty (infracoccygeal sacropexy); sacrospinous colpopexy
      (vaginal sacral colpopexy); sutures; traditional anterior colporrhaphy; transanal
      repair; ultralateral anterior colporrhaphy alone or with cadaveric fascia patch;
      vaginal hysterectomy; vaginal oestrogen; vaginal pessaries; and vaginal
      sacrospinous colpopexy.

PMID- 22414611
TI  - Counteracting tinnitus by acoustic coordinated reset neuromodulation.
AB  - PURPOSE: Subjective tinnitus is associated with pathologic enhanced neuronal
      synchronization. We used a model based desynchronization technique, acoustic
      coordinated reset (CR) neuromodulation, to specifically counteract tinnitus
      related neuronal synchrony thereby inducing an unlearning of pathological
      synaptic connectivity and neuronal synchrony. METHODS: In a prospective,
      randomized, single blind, placebo-controlled trial in 63 patients with chronic
      tonal tinnitus and up to 50 dB hearing loss we studied safety and efficacy of
      different doses of acoustic CR neuromodulation. We measured visual analogue scale
      and tinnitus questionnaire (TQ) scores and spontaneous EEG. RESULTS: CR treatment
      was safe, well-tolerated and caused a significant decrease of tinnitus loudness
      and symptoms. Placebo treatment did not lead to any significant changes. Effects
      gained in 12 weeks of treatment persisted through a preplanned 4-week therapy
      pause and showed sustained long-term effects after 10 months of therapy:
      response, i.e. a reduction of at least 6 TQ points, was obtained in 75% of
      patients with a mean TQ reduction of 50% among responders. CR therapy
      significantly lowered tinnitus frequency and reversed the tinnitus related EEG
      alterations. CONCLUSION: The CR-induced reduction of tinnitus and underlying
      neuronal characteristics indicates a new non-invasive therapy which might also be
      applicable to other conditions with neuronal hypersynchrony.

PMID- 22414612
TI  - Synthesis and evaluation of 1-(substituted)-3-prop-2-ynylureas as antiangiogenic
      agents.
AB  - Novel urea derivatives of alkynes have been designed, synthesized, and evaluated
      as potential cancer therapeutics leads. The most active 1-((3
      chloromethyl)phenyl)-3-prop-2-ynylurea (1) exhibited cytotoxic effect against
      HELA and MCF-7 cell lines with IC(50) values of 1.55 MUM and 1.48 MUM,
      respectively. Further investigation on tube formation assay in human vein
      umbilical cells (HUVEC) demonstrated that 1 and methyl 4-(3-(3
      ethynylureido)benzyloxy) benzoate (6) possess antiangiogenic activity, with
      minimum effective dose of 25 nM (for 1) and 6.25 MUM (for 6). The ED(50) of 1 and
      6 were found to be 0.26 MUM and 17.52 MUM, respectively. The results from in
      vitro tyrosine kinase assay indicated the EGFR inhibition of 1 over other kinases
      (VEGFR2, FGFR1 and PDGFRbeta). The cytotoxicity of 1 against EGFR overexpressing
      cell line A431 (IC(50) 36 nM) was comparable to that of erlotinib. The binding
      mode of 1 from docking simulation in the EGFR active site revealed that the urea
      motif formed hydrogen bonding with Lys745, Thr854 and Asp855 in hydrophobic
      pocket of EGFR. Compound 1 is considered as a potential lead for further
      optimization.

PMID- 22414613
TI  - Synthesis and biological evaluation of novel small non-peptidic HIV-1 PIs: the
      benzothiophene ring as an effective moiety.
AB  - Synthesis and biological evaluation of a new series of potential HIV-1 protease
      inhibitors incorporating different heterocycles are described. The variation of
      heteroatom in such molecules has displayed totally different biological
      activities and a benzothiophene containing inhibitor has shown high potency
      against wild type HIV-1 protease with IC(50)=60 nM, thanks to the lower
      desolvation penalty to be payed by such hydrophobic moiety.

PMID- 22414615
TI  - An N200 speller integrating the spatial profile for the detection of the non
      control state.
AB  - The N200 speller is a recently developed non-flashing visual brain-computer
      interface (BCI) paradigm utilizing the overt attention modulation effects on
      motion-onset visual evoked potentials (mVEP). In this study, a novel algorithm is
      proposed and applied in an online N200 speller. The proposed algorithm integrates
      the spatial information of the speller matrix to provide a more precise
      description of the mVEP response patterns, which is defined as the 'spatial
      profile'. More importantly, only control state data are used in the algorithm to
      train a classifier that nonetheless can detect the non-control state effectively.
      Compared to an algorithm with similar structure but not using the spatial profile
      information, the proposed algorithm shows significantly higher performance for
      the recognition of the non-control state while achieving a comparable performance
      for classifying different control states. Offline and online classification
      results show that the proposed N200 speller is a promising step toward a
      practical, online non-flashing BCI system for daily use.

PMID- 22414614
TI  - Phosphonium lipocations as antiparasitic agents.
AB  - Phosphonium lipocations were synthesized and evaluated for inhibition of the
      development of Plasmodium falciparum and Trypanosoma cruzi, etiological agents of
      malaria and Chagas disease, respectively. Optimal phthalimides and 1,4
      naphthoquinone-based lipocations were active in vitro at mid-high nM
      concentrations against P. falciparum and low MUM concentrations against T. cruzi.

PMID- 22414616
TI  - Striatal dysfunction during failed motor inhibition in children at risk for
      bipolar disorder.
AB  - BACKGROUND: A better understanding of the neural underpinnings of bipolar
      disorder (BD) can be obtained by examining brain activity in symptom-free
      individuals at risk for BD. This study examined the neural correlates of motor
      inhibition in a sample of symptom-free youths at familial risk for BD. METHODS:
      19 euthymic youths with BD, 13 asymptomatic youths with a first-degree relative
      with BD, and 21 healthy comparison children completed the stop signal task in a 3
      T scanner. RESULTS: Children at familial risk for BD exhibited increased putamen
      activation during unsuccessful inhibition that distinguished them from both
      healthy and BD children. Youths with BD exhibited reduced activation of the right
      nucleus accumbens during unsuccessful inhibition as compared to the other
      participant groups. CONCLUSIONS: Striatal activation patterns differ between
      youths at risk for BD and healthy comparison children during a motor inhibition
      task.

PMID- 22414617
TI  - Angiotensin-(1-7) induces peripheral antinociception through mas receptor
      activation in an opioid-independent pathway.
AB  - The G protein-coupled receptor Mas was recently described as an angiotensin-(1-7)
      [Ang-(1-7)] receptor. In the present study, we demonstrate an antinociceptive
      effect of Ang-(1-7) for the first time. Additionally, we evaluated the anatomical
      localization of Mas in the dorsal root ganglia using immunofluorescence. This is
      the first evidence indicating that this receptor is present in sensitive neurons.
      The antinociceptive effect was demonstrated using the rat paw pressure test. For
      this test, sensitivity is increased by intraplantar injection of prostaglandin
      E(2). Ang-(1-7) administered locally into the right hind paw elicited a dose
      dependent antinociceptive effect. Because the higher dose of Ang-(1-7) did not
      produce an effect when injected into the contralateral paw, this effect was
      considered local. The specific antagonist for the Mas receptor, A-779, inhibited
      the peripheral antinociception induced by exposure to 4 MUg/paw Ang-(1-7) in a
      dose-dependent manner. The highest dose completely reversed the antinociceptive
      effect induced by Ang-(1-7), suggesting that the Mas receptor is an obligatory
      component in this process and that other angiotensin receptors may not be
      involved. When injected alone, the antagonist was unable to induce hyperalgesia
      or antinociception. Alternatively, naloxone was unable to inhibit the
      antinociceptive effect induced by Ang-(1-7), suggesting that endogenous opioid
      peptides may not be involved in this response. These data provide the first
      anatomical basis for the physiological role of Ang-(1-7) in the modulation of
      pain perception via Mas receptor activation in an opioid-independent pathway.
      Taken together, these results provide new perspectives for the development of a
      new class of analgesic drugs.

PMID- 22414618
TI  - Sexuality, aging, and dementia.
AB  - BACKGROUND: Sexuality in later life and its relationship to dementia is a
      neglected topic: greater understanding of the area has the potential to
      contribute to the quality of life of people with dementia, their family members,
      and formal carers. We review current knowledge about sexuality, aging, and
      dementia. METHODS: We undertook a review of the recent literature to examine of
      the following areas: what is known about sexuality and aging, and about attitudes
      to sexuality and aging; what is known about the relevance of sexuality and aging
      to people living with dementia and their care; and the management of sexual
      behaviors causing concern to others. RESULTS: Sexual activity decreases in
      frequency with increasing age but many older people remain sexually active; there
      is no age limit to sexual responsiveness; and sexuality is becoming more
      important to successive cohorts of older people, including people living with
      dementia and gay, lesbian, bisexual, and transgendered elderly people. Attitudes
      and beliefs toward sexuality and aging are strongly influenced by stereotypes and
      myths, not only among the general public but also among those working in health
      and social care. CONCLUSIONS: Professional bodies should include sexuality,
      aging, and dementia in their training curricula. More work is needed on the
      impact of environmental issues, particularly in group living situations, on older
      adults' sexuality, and on consent issues. Ethical decision-making frameworks can
      be useful in practice. Organizations should investigate how to support staff in
      avoiding a problem-orientated approach and focus on providing holistic person
      centered care.

PMID- 22414620
TI  - Sustained release of PTH(1-34) from PLGA microspheres suppresses osteoarthritis
      progression in rats.
AB  - We previously reported that PTH(1-34) inhibits the terminal differentiation of
      articular chondrocytes and, in turn, suppresses the progression of osteoarthritis
      (OA). However, this treatment requires an injection of PTH(1-34) once every 3
      days over the treatment period. In this study, we studied the effect of sustained
      administration of PTH(1-34) in a papain-induced OA rat model. We developed an
      effective controlled-release system for prolonging the treatment duration of an
      intra-articular injection for OA treatment in rats. The effects of released PTH(1
      34) from PLGA(65:35)-encapsulated PTH(1-34) microspheres (PTH/PLGA) on papain
      induced OA in rat knees were studied. Microsphere morphology was observed in
      vitro by scanning electron microscopy, and microsphere size was determined with a
      particle size analyzer. The PTH(1-34) encapsulation efficiency and release
      profile, as well as the toxicity of PTH/PLGA, were examined. The bioactivity of
      released PTH(1-34) was tested by examining cAMP levels in MC3T3E1 cells. In vivo,
      we evaluated the changes of localized GAG, Col II, and Col X in the articular
      cartilage of rat knees. Our results demonstrated that the surface of the PLGA
      microspheres was smooth, and the size of the microspheres was in the range of 51
      127 MUm. PTH/PLGA microspheres sustainably released PTH(1-34) for 19 days with a
      concentration range of 0.01-100 nM that covered the expected concentration of
      10nM at 37 degrees C. The cAMP levels of MC3T3E1 cells were elevated in the
      response to released PTH(1-34) from PTH/PLGA microspheres, indicating that the
      released PTH(1-34) is bioactive. Most importantly, intra-articular treatment with
      either PTH(1-34) (0.1-100 nM) 3 days/injection or PTH/PLGA microspheres (15
      days/injection) for 5 weeks revealed the similar effect on suppressing papain
      induced OA changes (decreasing GAG and Col II and increasing Col X) in rat knee
      cartilage. The effect of PTH/PLGA microspheres on suppressing OA progression was
      similar to that of a once-every-three-day injection of PTH(1-34), indicating that
      both the sustained and intermittent action of PTH(1-34) effectively suppress OA
      progression. The developed PLGA microspheres with sustained release and long-term
      effect may be potent carriers for PTH(1-34) used to treat early OA.

PMID- 22414621
TI  - Osteostatin-loaded onto mesoporous ceramics improves the early phase of bone
      regeneration in a rabbit osteopenia model.
AB  - Parathyroid hormone-related protein (PTHrP) is an important modulator of bone
      formation. Recently, we reported that PTHrP (107-111) (osteostatin) coating onto
      mesoporous ceramics confers osteogenic activity to these materials. Bone repair
      is dramatically compromised in osteopenia/osteoporosis. Thus, we examined the
      efficacy of unmodified and organically modified SBA15 ceramics loaded with
      osteostatin in promoting bone repair in an osteoporotic rabbit model.
      Osteoporosis was induced in New Zealand rabbits by methylprednisolone
      administration, and healthy rabbits were used as controls. Tested materials were
      implanted into a femoral cavitary defect, and animals were sacrificed at 2 weeks
      post-implantation. At this time, implants were encapsulated by a variable layer
      of fibrotic tissue with no evidence of inflammation. Similarly to observations in
      normal rabbits, both types of osteostatin-loaded bioceramics induced tissue
      regeneration associated with increased staining for PCNA, Runx2, osteopontin,
      and/or vascular endothelial growth factor in osteoporotic rabbits. Our present
      findings demonstrate that these osteostatin-bearing bioceramics increase the
      early repair response not only in normal bone but also in osteoporotic bone after
      a local injury.

PMID- 22414622
TI  - Collateral damage and compensatory changes after injection of a toxin targeting
      neurons with the neurokinin-1 receptor in the nucleus tractus solitarii of rat.
AB  - Injection into the nucleus tractus solitarii (NTS) of toxins that target
      substance P (SP) receptors ablates neurons that express neurokinin-1 (NK1)
      receptors, attenuates baroreflexes, and results in increased lability of arterial
      pressure. We and others have shown that the toxin leads to loss of neurons
      containing SP receptors and loss of GABAergic neurons in the NTS; but given that
      neither type neuron is thought to be integral to baroreflex transmission in NTS,
      mechanisms responsible for the cardiovascular changes remained unclear. Because
      NK1 receptors colocalize with N-methyl-d-aspartate (NMDA) receptors and alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in NTS and
      because glutamate transmission may be integral to baroreflex transmission in the
      NTS we hypothesized that the toxic lesions may interrupt mechanisms for glutamate
      transmission. Interruption of those mechanisms could be responsible for the
      cardiovascular effects. We tested the hypothesis by performing fluorescent
      immunohistochemistry, confocal microscopy and image analysis after injecting
      stabilized SP-SAP (SSP-SAP) unilaterally into the NTS. We assessed changes in
      immunoreactivity (IR) of NMDA receptor subunit 1 (NMDAR1), AMPA receptor subunit
      2 (GluR2), and 3 types of vesicular glutamate transporters (VGluT) as well as IR
      of gamma-aminobutyric acid receptors type b (GABAb), neuronal nitric oxide
      synthase (nNOS), tyrosine hydroxylase (TH), and protein gene product 9.5 (PGP
      9.5), a neuronal marker, in the NTS. When compared to that of the same section of
      the un-injected NTS, IR decreased significantly in the injected side for NMDAR1
      (p<0.01), GluR2 (p<0.01), VGluT3 (p<0.01), GABAb (p<0.001), and PGP9.5 (p<0.001).
      In contrast, IR for VGluT1 (p<0.001), VGluT2 (p<0.001), nNOS (p<0.001), and TH
      (p<0.001) increased significantly. We conclude that pathologic effects following
      ablation of neurons with NK1 receptors in NTS may result from interruption of
      neurotransmission through other neurochemical systems associated with NK1
      receptors-containing neurons.

PMID- 22414619
TI  - The dentin organic matrix - limitations of restorative dentistry hidden on the
      nanometer scale.
AB  - The prevention and treatment of dental caries are major challenges occurring in
      dentistry. The foundations for modern management of this dental disease,
      estimated to affect 90% of adults in Western countries, rest upon the dependence
      of ultrafine interactions between synthetic polymeric biomaterials and
      nanostructured supramolecular assemblies that compose the tooth organic
      substrate. Research has shown, however, that this interaction imposes less than
      desirable long-term prospects for current resin-based dental restorations. Here
      we review progress in the identification of the nanostructural organization of
      the organic matrix of dentin, the largest component of the tooth structure, and
      highlight aspects relevant to understating the interaction of restorative
      biomaterials with the dentin substrate. We offer novel insights into the
      influence of the hierarchically assembled supramolecular structure of dentin
      collagen fibrils and their structural dependence on water molecules. Secondly, we
      review recent evidence for the participation of proteoglycans in composing the
      dentin organic network. Finally, we discuss the relation of these complexly
      assembled nanostructures with the protease degradative processes driving the low
      durability of current resin-based dental restorations. We argue in favour of the
      structural limitations that these complexly organized and inherently hydrated
      organic structures may impose on the clinical prospects of current hydrophobic
      and hydrolyzable dental polymers that establish ultrafine contact with the tooth
      substrate.

PMID- 22414623
TI  - Cytokines profiling by multiplex analysis in experimental arthritis: which
      pathophysiological relevance for articular versus systemic mediators?
AB  - INTRODUCTION: We have taken advantage of the large screening capacity of a
      multiplex immunoassay to better define the respective contribution of articular
      versus systemic cytokines in experimental arthritis. METHODS: We performed a
      follow up (from 7 hours to 14 days) multiplex analysis of 24 cytokines in
      synovial fluid and sera of rats developing Antigen-Induced Arthritis (AIA) and
      confronted their protein level changes with molecular, biochemical, histological
      and clinical events occurring in the course of the disease. RESULTS: The time
      scheduled findings in arthritic joints correlated with time-dependent changes of
      cytokine amounts in joint effusions but not with their blood levels. From seven
      hours after sensitization, high levels of chemokines (MCP-1, MIP1alpha, GRO/KC,
      RANTES, eotaxin) were found in synovial fluid of arthritic knees whereas
      perivascular infiltration occurred in the synovium; local release of inflammatory
      cytokines (IFNgamma, IL-1beta, IL-6) preceded the spreading of inflammation and
      resulted in progressive degradation of cartilage and bone. Finally a local
      overexpression of several cytokines/adipocytokines poorly described in arthritis
      (IL-13, IL-18, leptin) was observed. CONCLUSIONS: Distinct panels of cytokines
      were found in arthritic fluid during AIA, and the expected effect of mediators
      correlated well with changes occurring in joint tissues. Moreover, multiplex
      analysis could be helpful to identify new pathogenic mediators and to elucidate
      the mechanisms supporting the efficacy of putative targeted therapies.

PMID- 22414624
TI  - Acute effects of different glycemic index diets on serum motilin, orexin and
      neuropeptide Y concentrations in healthy individuals.
AB  - AIM: To determine whether different glycemic index (GI) diets have different
      effects on the acute secretion of motilin, orexin and neuropeptide Y (NPY),
      regulators of food intake, energy homeostasis and glucose metabolism. METHODS:
      Fifty healthy volunteers were randomly assigned to two groups and were fed an
      isocaloric breakfast (464 kcal) containing high GI (HGI; GI=90) or low GI (LGI;
      GI=47) components. Serum motilin, orexin, and NPY concentrations were measured
      before (0 h) and 2h after the meal. RESULTS: The concentrations of motilin,
      orexin-A, NPY, C-peptide, and blood glucose at 0 h were similar in both groups of
      subjects. However, 2 h after breakfast, the serum motilin, NPY, C-peptide, and
      blood glucose concentrations were increased and orexin-A concentrations were
      decreased in both groups. The percentage changes from 0 to 2 h [(2-h value-0-h
      value)/baseline*100)] in motilin (27.72+/-2.46% vs. 20.95+/-2.06%, p=0.04) and
      orexin-A (9.15+/-2.06% vs. 3.49+/-1.67%, p=0.038) concentrations were
      significantly higher in the LGI group than in the HGI group. By contrast, the
      percentage changes in NPY (53.7+/-9.73% vs. 28.1+/-5.2%, p=0.026) and blood
      glucose (12.3+/-3.78% vs. 1.77+/-2.52%, p=0.025) concentrations were
      significantly greater in the HGI group than in the LGI group. Although C-peptide
      concentrations increased significantly after breakfast in both groups, the
      magnitude of the increase was similar (132.69+/-25.15% vs. 139.98+/-27.29%,
      p=0.845). Motilin and NPY concentrations were moderately positive correlated
      (r=0.410, p=0.042), while orexin-A and NPY concentrations were negatively
      correlated (r=-0.429, p=0.033) at 2h in the LGI group. CONCLUSIONS: A breakfast
      with a LGI reduced the secretion of orexin-A but significantly stimulated motilin
      secretion, without marked effects on the secretion of NPY. Therefore, consumption
      of a LGI diet may help to regulate food intake and energy expenditure in healthy
      individuals based on the changes in these hormones.

PMID- 22414626
TI  - Topical treatment habits in psoriasis patients receiving adalimumab.
AB  - BACKGROUND: Biologics are used increasingly to treat moderate-to-severe
      psoriasis. Here the topical treatment habits (corticosteroids and vitamin D
      derivates) and moisturizer use of 97 Swiss patients (male 65, female 32)
      receiving adalimumab have been evaluated. METHODS: Using a short cross-sectional
      survey the pharmacist asked patients during telephone contact about their topical
      treatment habits and psoriasis activity. RESULTS: 47 patients with adalimumab
      monotherapy were still free of psoriatic lesions after a longer follow-up of 13
      months of therapy; 8 of them still used topical treatment. In contrast, 38 of 50
      patients with remaining lesions used topicals. More than 75% of patients
      indicated that the perceived efficacy of additional topical therapy was >=5 on a
      visual analog scale (0-10). The use of moisturizers did not correlate with
      disease activity. CONCLUSION: Topical treatment use by adalimumab patients is
      associated with remaining disease activity. 83% of patients without residual
      plaques (40% of all adalimumab patients) are able to stop topical treatment
      completely.

PMID- 22414625
TI  - Association of a genetic polymorphism of the alcohol-metabolizing enzyme ADH1C
      with alcohol dependence: results of a case-control study.
AB  - OBJECTIVE: Alcohol dependence causes serious problems which may be influenced by
      genetic factors associated with alcohol metabolism. The aim was to investigate
      the allelic and genotypic difference in distribution of a polymorphism in alcohol
      dehydrogenase 1C gene (ADH1C) between alcohol-dependent individuals and controls,
      and to examine if these genotypes were associated with the age at which the
      patient became alcohol-dependent. METHODS: We conducted a case-control study
      including 90 alcohol-dependent cases and 100 historic controls. The genomic DNA
      was isolated and the alleles were analyzed with an RFLP. RESULTS: The ADH1C*1
      allele frequencies were 0.89 (95% CI 0.84-0.91) in controls and 0.68 (95% CI 0.61
      0.74) in alcohol-dependent patients. The frequencies of the ADH1C*2 allele were
      0.11 (95% CI 0.07-0.14) and 0.32 (95% CI 0.25-0.38) among controls and alcohol
      dependent patients, respectively (p < 0.0001). The ADH1C*1/*1 genotype frequency
      was significantly higher in the control group (77%) compared to that of the
      alcohol-dependents (51%, p < 0.0001). The ADH1C*1/*2 genotype frequency was
      significantly lower in the control group (23%) compared to that of the alcohol
      dependents (42%, p < 0.0001). We obtained no statistically significant difference
      among the ADH1C genotype groups regarding age. CONCLUSIONS: These findings
      suggest that a significantly higher presence of ADH1C*2 allele is associated with
      alcohol dependence in a Turkish population. Studies with other related
      polymorphisms are needed to more precisely estimate the association of alcohol
      dependence with ADH1C.

PMID- 22414627
TI  - Skeletal muscle involvement in myotonic dystrophy type 2. A comparative muscle
      ultrasound study.
AB  - This study determines the presence and extent of muscle changes in 31 myotonic
      dystrophy type 2 (DM2) patients detected by muscle ultrasound. Results were
      compared to 31 adult-onset myotonic dystrophy type 1 patients (DM1) and healthy
      controls. Furthermore, we tested the hypothesis that structural muscle changes
      correlate with age, quantitative muscle force and serum creatine kinase in both
      disorders. In DM2 all seven examined muscles (right masseter muscle, right and
      left biceps brachii, right and left forearm flexors, right rectus femoris, and
      left tibialis anterior muscle) showed increased mean echo intensities (p <=
      0.001). Atrophy of the masseter muscle and rectus femoris were both found in 23%
      of DM2 patients. Muscle thickness was significantly more decreased in the elbow
      flexors in DM2 compared to DM1. Echo intensity sum score correlated positively
      with age in DM2 (r=0.57, p=0.001) and negatively with muscle force (r=0.36,
      p=0.048). We conclude that all tested muscles are affected and structurally
      abnormal in DM2 patients. Proximal arm muscles are more affected in DM2 compared
      to DM1, which corresponds to clinical findings.

PMID- 22414628
TI  - Nongenomic effects of thyroid hormones on the immune system cells: New targets,
      old players.
AB  - It is now widely accepted that thyroid hormones, l-thyroxine (T(4)) and 3,3',5
      triiodo-l-thyronine (T(3)), act as modulators of the immune response. Immune
      functions such as chemotaxis, phagocytosis, generation of reactive oxygen
      species, and cytokine synthesis and release, are altered in hypo- and hyper
      thyroid conditions, even though for many immune cells no clear correlation has
      been found between altered levels of T(3) or T(4) and effects on the immune
      responses. Integrins are extracellular matrix proteins that are important
      modulators of many cellular responses, and the integrin alphavbeta3 has been
      identified as a cell surface receptor for thyroid hormones. Rapid signaling via
      this plasma membrane binding site appears to be responsible for many nongenomic
      effects of thyroid hormones, independent of the classic nuclear receptors.
      Through the integrin alphavbeta3 receptor the hormone can activate both the
      ERK1/2 and phosphatidylinositol 3-kinase pathways, with downstream effects
      including intracellular protein trafficking, angiogenesis and tumor cell
      proliferation. It has recently become clear that an important downstream target
      of the thyroid hormone nongenomic pathway may be the mammalian target of
      rapamycin, mTOR. New results demonstrate the capability of T(3) or T(4) to induce
      in the short time range important responses related to the immune function, such
      as reactive oxygen species production and cell migration in THP-1 monocytes. Thus
      thyroid hormones seem to be able to modulate the immune system by a combination
      of rapid nongenomic responses interacting with the classical nuclear response.

PMID- 22414629
TI  - Non-genomic effects of vitamin D in human spermatozoa.
AB  - The spectrum for vitamin D (VD) mediated effects has expanded in recent years.
      Activated VD (1,25(OH)(2)D(3)) binds to the VD receptor (VDR) and mediates non
      genomic effects through the alternative ligand binding-pocket (VDR-ap) or
      regulates gene transcription through the genomic binding-pocket. VDR and VD
      metabolizing enzymes are expressed in human testis, male reproductive tract and
      mature spermatozoa, and VD is considered important for male reproduction.
      Expression of the VD-inactivating enzyme CYP24A1 at the annulus of human
      spermatozoa distinguish normal and infertile men with high specificity, and
      CYP24A1 expression is positively correlated with all semen variables and
      suggested as a marker for both semen quality and VD responsiveness. Moreover,
      spermatozoa are transcriptionally silent and are therefore a unique model to
      study non-genomic effects. 1,25(OH)(2)D(3) induced a rapid increase in
      intracellular calcium concentration [Ca(2+)](i) in human spermatozoa. The
      [Ca(2+)](i) increase was abrogated by the non-genomic VDR antagonist
      1beta,25(OH)(2)D(3), while the specific agonist for VDR-ap (JN) increased
      [Ca(2+)](i) with similar kinetics as 1,25(OH)(2)D(3). The rise in [Ca(2+)](i)
      originated as a Ca(2+)-release from intracellular stores since inhibition of
      phospholipase-C diminished the 1,25(OH)(2)D(3) mediated Ca(2+) response, while
      suspending spermatozoa in a nominally Ca(2+)-free medium did not affect the VD
      mediated Ca(2+) rise. The spatio-temporal kinetics of the VD-response differed
      from the progesterone-mediated increase in [Ca(2+)](i) as the VD-mediated Ca(2+)
      rise was not observed in the tail region and was independent of extracellular
      Ca(2+). A functional role of the VD-mediated Ca(2+) increase was supported by
      showing that 1,25(OH)(2)D(3) increased sperm motility and induced the acrosome
      reaction in vitro.

PMID- 22414630
TI  - Outcome of repeat supratrigonal obstetric vesicovaginal fistula repair after
      previous failed repair.
AB  - INTRODUCTION: Currently, surgical repair for vesicovaginal fistula (VVF) provides
      excellent results, but the recurrent VVF is difficult to treat as compared to
      primary. PATIENTS AND METHODS: Sixty-eight patients (44 primipara and 24
      multipara) with recurrent VVF repair from January 2002 to December 2007 were
      included in present study. The mean size of fistula was 2.8 cm (1.0-6.5). The
      previous surgical repair was through the abdominal route in 50 patients (73.53%)
      and through the vaginal route in the remaining 18 patients (26.47%). RESULTS: The
      procedure was successful in 62 of 68 patients (91.17%). The mean duration of
      surgery was 146.6 min (100-210). Mean blood loss was 160 ml (110-400) and mean
      hospital stay was 5.6 days (4-10). Eight patients developed complications.
      CONCLUSION: Recurrent VVF is difficult to treat, but excellent results can still
      be achieved by strictly sticking to the principals of surgical repair for VVF.

PMID- 22414631
TI  - Fibromyalgia, mood disorders, and intense creative energy: A1AT polymorphisms are
      not always silent.
AB  - Persons with single copies of common alpha-1-antitrypsin polymorphisms such as S
      and Z are often considered "silent carriers". Published evidence however supports
      a complex behavioral phenotype or trait - intense creative energy ("ICE")
      associated with A1AT polymorphisms. We now confirm that phenotype and present an
      association of fibromyalgia syndrome (FMS) and A1AT in a consecutive series of
      neurological patients. This is a retrospective case control series of 3176
      consecutive patients presenting to Duke University Memory Clinic (747 patients)
      and to regional community-based Caldwell Hospital Neurology and Memory center
      (2429 patients). Work-up included medical history and examination, psychological
      evaluation, and genetic analysis. Chronic widespread pain (CWP) or FMS were
      diagnosed according to clinical guidelines, mostly as secondary diagnoses.
      Neurological patients carrying A1AT polymorphisms were common (ca 16% prevalence)
      and carriers had significantly higher use of inhaler and anxiolytic medications.
      Patients with ICE phenotype had a significantly higher proportion of A1AT
      polymorphisms (42%) compared to non-ICE patients (13%). Presence of CWP or FMS
      was common (14-22%) with average age at presentation of 56 years old and mostly
      female gender (82%). Patients with CWP/FMS had again significantly higher
      proportion of A1AT polymorphisms (38%) compared to other neurological patients
      (13%). Patients with anxiety disorders, bipolar I or bipolar II disorders or PTSD
      also had increased proportion of A1AT polymorphisms and significant overlap with
      ICE and FMS phenotype. Significant reductions in CWP/FMS prevalence are seen in
      apolipoprotein E4 carriers and methylene tetrahydrofolate reductase (MTHFR)
      mutation homozygotes. Since ICE phenotype is reported as a lifelong behavioral
      attribute, the presumption is that A1AT carriers have fundamental differences in
      brain development and inflammatory response. In support of this concept is
      finding those persons reporting a diagnosis of juvenile rheumatoid or idiopathic
      arthritis (JRA, JIA) had a significantly high proportion of A1AT polymorphisms
      (63%), suggesting a spectrum for JRA to later FMS presentations. Likewise,
      persons reporting a history of attention deficit disorder (ADD) had an increased
      proportion of A1AT polymorphisms (26%) compared to non-ADD persons (13%). Toxic
      environmental exposures are common (23%) and associated with diagnoses of PSP,
      PPA, FTD, FTD-PD, PD and ADVD. A1AT carriers were increased in cases of toxic
      exposure and PSP, PPA and FTD-PD. Our findings support the ICE behavioral
      phenotype for A1AT polymorphism carriers and the reported association with
      anxiety and bipolar spectrum disorders. We now extend that phenotype to apparent
      vulnerability to inflammatory muscle disease in a spectrum from JRA to
      fibromyalgia (FMS) and specific behavioral subsets of ADD, PTSD, and specific
      late onset neurological syndromes (FTD-PD and PPA). High and low risk FMS subsets
      can be defined using A1AT, MTHFR and APOE genotyping. Clinical diagnoses
      associated with A1AT polymorphisms included fibromyalgia, JRA/JIA, bipolar
      disorder, PTSD, primary progressive aphasia and FTDPD, but not most Alzheimer
      Disease subtypes. These results support an extended phenotype for A1AT mutation
      carriers beyond liver and lung vulnerability to selective advantages: ICE
      phenotype and disadvantages: fibromyalgia, affective disorders, and selected late
      onset neurological syndromes.

PMID- 22414632
TI  - 18F-FDG PET as a surrogate biomarker in non-small cell lung cancer treated with
      erlotinib: newly identified lesions are more informative than standardized uptake
      value.
AB  - This study assesses the predictive value of (18)F-FDG PET for overall survival in
      lung cancer patients treated with a targeted drug. METHODS: (18)F-FDG PET was
      performed in 125 second- or third-line non-small cell lung cancer (NSCLC)
      patients with a baseline Eastern Cooperative Oncology Group performance status
      less than 3 before treatment with erlotinib (150 mg daily) and 2 wk into
      treatment. The predictive value of (18)F-FDG PET, clinical parameters, and
      epithelial growth factor receptor (EGFR) mutation status for survival duration
      was evaluated by fitting accelerated failure time models. RESULTS: New lesions on
      PET at 2 wk, EGFR mutation status, performance status, and baseline tumor burden
      were independent and significant predictors of overall survival. Reduction of
      maximum standardized uptake value by at least 35% was predictive of survival only
      when EGFR mutation status was not accounted for. CONCLUSION: (18)F-FDG PET in
      second- or third-line NSCLC patients at 2 wk after starting treatment with
      erlotinib carries information about overall survival. Parametric survival
      modeling enables a quantitative assessment of the predictive value of (18)F-FDG
      PET in the context of clinical and laboratory information. New-lesion status by
      (18)F-FDG PET at 2 wk is a potential surrogate biomarker for survival in NSCLC.

PMID- 22414633
TI  - Bone marrow dosimetry using 124I-PET.
AB  - Bone marrow is usually dose-limiting for radioimmunotherapy. In this study, we
      directly estimated red marrow activity concentration and the self-dose component
      of absorbed radiation dose to red marrow based on PET/CT of 2 different (124)I
      labeled antibodies (cG250 and huA33) and compared the results with plasma
      activity concentration and plasma-based dose estimates. METHODS: Two groups of
      patients injected with (124)I-labeled monoclonal antibodies (11 patients with
      renal cancer receiving (124)I-cG250 and 5 patients with colorectal cancer
      receiving (124)I- huA33) were imaged by PET or PET/CT on 2 or 3 occasions after
      infusion. Regions of interest were drawn over several lumbar vertebrae, and red
      marrow activity concentration was quantified. Plasma activity concentration was
      also quantified using multiple patient blood samples. The red marrow-to-plasma
      activity concentration ratio (RMPR) was calculated at the times of imaging. The
      self-dose component of the absorbed radiation dose to the red marrow was
      estimated from the images, from the plasma measurements, and using a combination
      of both sets of measurements. RESULTS: RMPR was observed to increase with time
      for both groups of patients. Mean (+/-SD) time-dependent RMPR (RMPR(t)) for the
      cG250 group increased from 0.13 +/- 0.06 immediately after infusion to 0.23 +/-
      0.09 at approximately 6 d after infusion. For the huA33 group, mean RMPR(t) was
      0.10 +/- 0.04 immediately after infusion, 0.13 +/- 0.05 approximately 2 d after
      infusion, and 0.20 +/- 0.09 approximately 7 d after infusion. Plasma-based
      estimates of red marrow self-dose tended to be greater than image-based values
      by, on average, 11% and 47% for cG250 and huA33, respectively, but by as much as 
      73% to 62% for individual patients. The hybrid method combining RMPR(t) and
      plasma activity concentration provided a closer match to the image-based dose
      estimates (average discrepancies, -2% and 18% for cG250 and huA33, respectively).
      CONCLUSION: These results suggest that the assumption of time-independent
      proportionality between red marrow and plasma activity concentration may be too
      simplistic. Individualized imaged-based dosimetry is probably required for the
      optimal therapeutic delivery of radiolabeled antibodies, which does not
      compromise red marrow and may allow, for some patients, a substantial increase in
      administered activity and thus tumor dose.

PMID- 22414634
TI  - Relative equilibrium plot improves graphical analysis and allows bias correction
      of standardized uptake value ratio in quantitative 11C-PiB PET studies.
AB  - Both the standardized uptake value ratio (SUVR) and the Logan plot result in
      biased distribution volume ratios (DVRs) in ligand-receptor dynamic PET studies.
      The objective of this study was to use a recently developed relative equilibrium
      based graphical (RE) plot method to improve and simplify the 2 commonly used
      methods for quantification of (11)C-Pittsburgh compound B ((11)C-PiB) PET.
      METHODS: The overestimation of DVR in SUVR was analyzed theoretically using the
      Logan and the RE plots. A bias-corrected SUVR (bcSUVR) was derived from the RE
      plot. Seventy-eight (11)C-PiB dynamic PET scans (66 from controls and 12 from
      participants with mild cognitive impaired [MCI] from the Baltimore Longitudinal
      Study of Aging) were acquired over 90 min. Regions of interest (ROIs) were
      defined on coregistered MR images. Both the ROI and the pixelwise time-activity
      curves were used to evaluate the estimates of DVR. DVRs obtained using the Logan
      plot applied to ROI time-activity curves were used as a reference for comparison
      of DVR estimates. RESULTS: Results from the theoretic analysis were confirmed by
      human studies. ROI estimates from the RE plot and the bcSUVR were nearly
      identical to those from the Logan plot with ROI time-activity curves. In
      contrast, ROI estimates from DVR images in frontal, temporal, parietal, and
      cingulate regions and the striatum were underestimated by the Logan plot
      (controls, 4%-12%; MCI, 9%-16%) and overestimated by the SUVR (controls, 8%-16%;
      MCI, 16%-24%). This bias was higher in the MCI group than in controls (P < 0.01)
      but was not present when data were analyzed using either the RE plot or the
      bcSUVR. CONCLUSION: The RE plot improves pixelwise quantification of (11)C-PiB
      dynamic PET, compared with the conventional Logan plot. The bcSUVR results in
      lower bias and higher consistency of DVR estimates than of SUVR. The RE plot and
      the bcSUVR are practical quantitative approaches that improve the analysis of
      (11)C-PiB studies.

PMID- 22414635
TI  - Glucose metabolism in the insula and cingulate is affected by systemic
      inflammation in humans.
AB  - Depression is associated with systemic inflammation, and the systemic
      inflammation caused by endotoxin administration elicits mild depressive symptoms
      such as fatigue and reduced interest. The neural correlates of depressive
      symptoms that result from systemic inflammation are poorly defined. The aim of
      this study was to use (18)F-FDG PET to identify brain regions involved in the
      response to endotoxin administration in humans. METHODS: Nine healthy subjects
      received double-blind endotoxin (0.8 ng/kg) and placebo on different days. (18)F
      FDG PET was used to measure differences in the cerebral metabolic rate of glucose
      in the following regions of interest: insula, cingulate, and amygdala. Serum
      levels of tumor necrosis factor-alpha and interleukin-6 were used to gauge the
      systemic inflammatory response, and depressive symptoms were measured with the
      Montgomery-Asberg Depression Rating Scale and other scales. RESULTS: Endotoxin
      administration was associated with an increase in Montgomery-Asberg Depression
      Rating Scale, increased fatigue, reduced social interest, increased levels of
      inflammatory cytokines, higher normalized glucose metabolism (NGM) in the insula,
      and, at a trend level, lower NGM in the cingulate. Secondary analyses of insula
      and cingulate subregions indicated that these changes were driven by the right
      anterior insula and the right anterior cingulate. There was a negative
      correlation between peak cytokine levels and change in social interest and
      between peak cytokine levels and change in insula NGM. There was a positive
      correlation between the change in NGM in the insula and change in social
      interest. CONCLUSION: Systemic inflammation in humans causes an increase in
      depressive symptoms and concurrent changes in glucose metabolism in the insula
      and cingulate-brain regions that are involved in interoception, positive
      emotionality, and motivation.

PMID- 22414636
TI  - In vivo evaluation of a cancer therapy strategy combining HSV1716-mediated
      oncolysis with gene transfer and targeted radiotherapy.
AB  - Oncolytic herpes viruses show promise for cancer treatment. However, it is
      unlikely that they will fulfill their therapeutic potential when used as
      monotherapies. An alternative strategy is to use these viruses not only as
      oncolytic agents but also as a delivery mechanism of therapeutic transgenes to
      enhance tumor cell killing. The herpes simplex virus 1 deletion mutant HSV1716 is
      a conditionally replicating oncolytic virus that selectively replicates in and
      lyses dividing tumor cells. It has a proven safety profile in clinical trials and
      has demonstrated efficacy as a gene-delivery vehicle. To enhance its therapeutic
      potential, we have engineered HSV1716 to convey the noradrenaline transporter
      (NAT) gene (HSV1716/NAT), whose expression endows infected cells with the
      capacity to accumulate the noradrenaline analog metaiodobenzylguanidine (MIBG).
      Thus, the NAT gene-infected cells are susceptible to targeted radiotherapy using
      radiolabeled (131)I-MIBG, a strategy that has already shown promise for combined
      targeted radiotherapy-gene therapy in cancer cells after plasmid-mediated
      transfection. METHODS: We used HSV1716/NAT as a dual cell lysis-gene delivery
      vehicle for targeting the NAT transgene to human tumor xenografts in vivo.
      RESULTS: In tumor xenografts that did not express NAT, intratumoral or
      intravenous injection of HSV1716/NAT induced the capacity for active uptake of
      (131)I-MIBG. Administration of HSV1716/NAT and (131)I-MIBG resulted in decreased
      tumor growth and enhanced survival relative to injection of either agent alone.
      Efficacy was dependent on the scheduling of delivery of the 2 agents. CONCLUSION:
      These findings support a role for combination radiotherapy-gene therapy for
      cancer using HSV1716 expressing the NAT transgene and targeted radionuclide
      therapy.

PMID- 22414637
TI  - Multifunctional profiling of non-small cell lung cancer using 18F-FDG PET/CT and
      volume perfusion CT.
AB  - The aim of this study was to investigate correlations between glucose metabolism
      registered by (18)F-FDG PET/CT and tumor perfusion quantified by volume perfusion
      CT and immunohistochemical markers Ki67 and microvessel density (MVD) in patients
      with non-small cell lung cancer (NSCLC). METHODS: Between February 2010 and April
      2011, 24 consecutive patients (21 women, 3 men; mean age +/- SD, 67.6 +/- 6.8 y;
      age range, 55.6-81.3 y) with histologically proven NSCLC (14 adenocarcinoma, 9
      squamous cell lung carcinoma [SCC], and 1 mixed adenocarcinoma and SCC) underwent
      (18)F-FDG PET/CT and additional volume perfusion CT. Maximum standardized uptake
      value (SUV(max)), mean SUV, and the metabolic tumor volume were used for (18)F
      FDG uptake quantification. Blood flow (BF), blood volume (BV), flow extraction
      product (K(trans)), and standardized perfusion value (SPV) were determined as CT
      perfusion parameters. Both perfusion parameters and (18)F-FDG uptake values were
      subsequently related to the histologic subtypes, proliferation marker Ki67, MVD
      according to CD34 staining, and total tumor volume. RESULTS: Mean SUV, SUV(max),
      and the metabolic tumor volume (mL) were 5.8, 8.7, and 32.3, respectively, in
      adenocarcinoma and 8.5, 12.9, and 16.8, respectively, in SCC. Mean BF (mL/100
      mL/min), mean BV (mL/100 mL), and K(trans) (mL/100 mL/min) were 35.4, 7.3, and
      27.8, respectively, in adenocarcinoma and 35.5, 10.0, and 27.8, respectively, in
      SCC. Moderate correlations were found between the (18)F-FDG PET/CT parameters and
      Ki67 as well as between CT perfusion parameters and MVD but not vice versa. For
      all tumors, the following correlations were found: between SUV(max) and Ki67, r =
      0.762 (P = 0.017); between SUV(max) and MVD, r = -0.237 (P = 0.359); between mean
      BF and Ki67, r = -0.127 (P = 0.626); and between mean BF and MVD, r = 0.467 (P =
      0.059). Interestingly, correlations between the BF-metabolic relationship and
      total tumor volume were higher in SCC (r = 0.762, P = 0.017) than in
      adenocarcinoma (r = -0.0791, P = 0.788). CONCLUSION: (18)F-FDG uptake correlates
      with Ki67, whereas BF, BV, and K(trans) correlate with MVD. Therefore, (18)F-FDG
      uptake and perfusion parameters provide complementary functional information. An
      improved tumor profiling will be beneficial for both prognosis and therapy
      response evaluation in these tumors.

PMID- 22414638
TI  - Initial results of simultaneous PET/MRI experiments with an MRI-compatible
      silicon photomultiplier PET scanner.
AB  - The most investigated semiconductor photosensor for MRI-compatible PET detectors
      is the avalanche photodiode (APD). However, the silicon photomultiplier (SiPM),
      also called the Geiger-mode APD, is gaining attention in the development of the
      next generation of PET/MRI systems because the SiPM has much better performance
      than the APD. We have developed an MRI-compatible PET system based on
      multichannel SiPM arrays to allow simultaneous PET/MRI. METHODS: The SiPM PET
      scanner consists of 12 detector modules with a ring diameter of 13.6 cm and an
      axial extent of 3.2 cm. In each detector module, 4 multichannel SiPM arrays (with
      4 * 4 channels arranged in a 2 * 2 array to yield 8 * 8 channels) were coupled
      with 20 * 18 Lu(1.9)Gd(0.1)SiO(5):Ce crystals (each crystal is 1.5 * 1.5 * 7 mm)
      and mounted on a charge division network for multiplexing 64 signals into 4
      position signals. Each detector module was enclosed in a shielding box to reduce
      interference between the PET and MRI scanners, and the temperature inside the box
      was monitored for correction of the temperature-dependent gain variation of the
      SiPM. The PET detector signal was routed to the outside of the MRI room and
      processed with a field programmable gate array-based data acquisition system. MRI
      compatibility tests and simultaneous PET/MRI acquisitions were performed inside a
      3-T clinical MRI system with 4-cm loop receiver coils that were built into the
      SiPM PET scanner. Interference between the imaging systems was investigated, and
      phantom and mouse experiments were performed. RESULTS: No radiofrequency
      interference on the PET signal or degradation in the energy spectrum and flood
      map was shown during simultaneous PET/MRI. The quality of the MRI scans acquired
      with and without the operating PET showed only slight degradation. The results of
      phantom and mouse experiments confirmed the feasibility of this system for
      simultaneous PET/MRI. CONCLUSION: Simultaneous PET/MRI was possible with a
      multichannel SiPM-based PET scanner, with no radiofrequency interference on PET
      signals or images and only slight degradation of the MRI scans.

PMID- 22414639
TI  - On the decoding of intracranial data using sparse orthonormalized partial least
      squares.
AB  - It has recently been shown that robust decoding of motor output from
      electrocorticogram signals in monkeys over prolonged periods of time has become
      feasible (Chao et al 2010 Front. Neuroeng. 3 1-10). In order to achieve these
      results, multivariate partial least-squares (PLS) regression was used. PLS uses a
      set of latent variables, referred to as components, to model the relationship
      between the input and the output data and is known to handle high-dimensional and
      possibly strongly correlated inputs and outputs well. We developed a new decoding
      method called sparse orthonormalized partial least squares (SOPLS) which was
      tested on a subset of the data used in Chao et al (2010) (freely obtainable from
      neurotycho.org (Nagasaka et al 2011 PLoS ONE 6 e22561)). We show that SOPLS
      reaches the same decoding performance as PLS using just two sparse components
      which can each be interpreted as encoding particular combinations of motor
      parameters. Furthermore, the sparse solution afforded by the SOPLS model allowed
      us to show the functional involvement of beta and gamma band responses in
      premotor and motor cortex for predicting the first component. Based on the
      literature, we conjecture that this first component is involved in the encoding
      of movement direction. Hence, the sparse and compact representation afforded by
      the SOPLS model facilitates interpretation of which spectral, spatial and
      temporal components are involved in successful decoding. These advantages make
      the proposed decoding method an important new tool in neuroprosthetics.

PMID- 22414640
TI  - Antioxidants and antioxidant treatment in disease.

PMID- 22414641
TI  - Fragrance material review on 2,4-dimethylbenzyl acetate.
AB  - A toxicologic and dermatologic review of 2,4-dimethylbenzyl acetate when used as
      a fragrance ingredient is presented. 2,4-Dimethylbenzyl acetate is a member of
      the fragrance structural group aryl alkyl alcohol simple acid esters (AAASAE).
      The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol
      with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate,
      acetate, propionate, butyrate, iso-butyrate and carbonate esters. This review
      contains a detailed summary of all available toxicology and dermatology papers
      that are related to this individual fragrance ingredient and is not intended as a
      stand-alone document. Available data for 2,4-dimethylbenzyl acetate were
      evaluated, then summarized, and includes: physical properties, acute toxicity,
      skin irritation, mucous membrane (eye) irritation, and skin sensitization data. A
      safety assessment of the entire AAASAE will be published simultaneously with this
      document. Please refer to Belsito et al. (2012) for an overall assessment of the
      safe use of this material and all AAASAE in fragrances.

PMID- 22414642
TI  - Fragrance material review on benzyl propionate.
AB  - A toxicologic and dermatologic review of benzyl propionate when used as a
      fragrance ingredient is presented. Benzyl propionate is a member of the fragrance
      structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The AAASAE
      fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a
      simple carboxylic acid (a chain of 1 to 4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for benzyl propionate were evaluated, then
      summarized, and includes: physical properties, acute toxicity, skin irritation,
      skin sensitization, elicitation, toxicokinetics, and genotoxicity data. A safety
      assessment of the entire AAASAE will be published simultaneously with this
      document. Please refer to Belsito et al. (2012) for an overall assessment of the
      safe use of this material and all AAASAE in fragrances.

PMID- 22414643
TI  - Fragrance material review on 4-methylbenzyl acetate.
AB  - A toxicologic and dermatologic review of 4-methylbenzyl acetate when used as a
      fragrance ingredient is presented. 4-Methylbenzyl acetate is a member of the
      fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The
      AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with
      a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for 4-methylbenzyl acetate were evaluated, then
      summarized, and includes: physical properties, skin irritation, skin
      sensitization, and elicitation data. A safety assessment of the entire AAASAE
      will be published simultaneously with this document. Please refer to Belsito et
      al. (2012) for an overall assessment of the safe use of this material and all
      AAASAE in fragrances.

PMID- 22414644
TI  - Fragrance material review on phenethyl acetate.
AB  - A toxicologic and dermatologic review of phenethyl acetate when used as a
      fragrance ingredient is presented. Phenethyl acetate is a member of the fragrance
      structural group aryl alkyl alcohol simple acid esters (AAASAE). The AAASAE
      fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a
      simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for phenethyl acetate were evaluated, then
      summarized, and includes: physical properties, acute toxicity, skin irritation,
      mucous membrane (eye) irritation, skin sensitization, elicitation,
      toxicokinetics, repeated dose, genotoxicity, and carcinogenicity data. A safety
      assessment of the entire AAASAE will be published simultaneously with this
      document. Please refer to Belsito et al. (2012) for an overall assessment of the
      safe use of this material and all AAASAE in fragrances.

PMID- 22414645
TI  - Fragrance material review on 1,1-dimethyl-2-phenylethyl butyrate.
AB  - A toxicologic and dermatologic review of 1,1-dimethyl-2-phenylethyl butyrate when
      used as a fragrance ingredient is presented. 1,1-Dimethyl-2-phenylethyl butyrate
      is a member of the fragrance structural group aryl alkyl alcohol simple acid
      esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an
      aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to
      generate formate, acetate, propionate, butyrate, isobutyrate and carbonate
      esters. This review contains a detailed summary of all available toxicology and
      dermatology papers that are related to this individual fragrance ingredient and
      is not intended as a stand-alone document. Available data for 1,1-dimethyl-2
      phenylethyl butyrate were evaluated, then summarized, and includes: physical
      properties, acute toxicity, skin irritation, mucous membrane (eye) irritation,
      skin sensitization, and genotoxicity data. A safety assessment of the entire
      AAASAE will be published simultaneously with this document. Please refer to
      Belsito et al. (2012) for an overall assessment of the safe use of this material
      and all AAASAE in fragrances.

PMID- 22414646
TI  - Regulation of renal organic anion and cation transporters by thymoquinone in
      cisplatin induced kidney injury.
AB  - In previous studies, we have demonstrated the biological activity of thymoquinone
      (TQ), an active compound extracted from the Nigella sativa plant, against
      cisplatin-induced neurotoxicity. Recenty, it was observed that there is an
      inherent lack in regulation of renal organic anion and cation transporters in
      cisplatin-induced nephrotoxicity. Here, we report, for the first time, the effect
      of TQ on alterations in the renal expression of organic anion transporters (OATs)
      and organic cation transporters (OCTs), as well as multidrug resistance
      associated proteins (MRPs) in rats treated with cisplatin. Twenty-eight 8-week
      old male Wistar rats were divided into four groups of control, TQ treated (10
      mg/kg b.w. in drinking water for 5 days), cisplatin (7 mg/kg b.w., i.p.) and TQ
      and cisplatin combination treatment. Cisplatin-induced malondialdehyde (MDA) and
      8-isoprostane increase was found to be markedly reduced in rats treated with TQ.
      In cisplatin only treated rats, the induced renal injury increased protein levels
      of the efflux transporters MRP2 and MRP4 while expression of OAT1, OAT3, OCT1 and
      OCT2 was reduced. In combination TQ- and cisplatin-treated rats, expression of
      MRP2 and MRP4 proteins was decreased in the kidneys. Conversely, TQ treatment
      increased levels of OCT1, OCT2, OAT1 and OAT3 and decreased levels of 8
      isoprostane and MDA levels in cisplatin-treated rats. In conclusion, the present
      study shows that the TQ synergizes with its nephroprotective effect against
      cisplatin-induced acute kidney injury in rats.

PMID- 22414647
TI  - Fragrance material review on carbonic acid, methyl phenylmethyl ester.
AB  - A toxicologic and dermatologic review of carbonic acid, methyl phenylmethyl ester
      when used as a fragrance ingredient is presented. Carbonic acid, methyl
      phenylmethyl ester is a member of the fragrance structural group Aryl Alkyl
      Alcohol Simple Acid Esters (AAASAE). The AAASAE fragrance ingredients are
      prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain
      of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate
      and carbonate esters. This review contains a detailed summary of all available
      toxicology and dermatology papers that are related to this individual fragrance
      ingredient and is not intended as a stand-alone document. Available data for
      carbonic acid, methyl phenylmethyl ester were evaluated, then summarized, and
      includes: physical properties, acute toxicity, skin irritation, and skin
      sensitization data. A safety assessment of the entire AAASAE will be published
      simultaneously with this document. Please refer to Belsito et al. (2012) for an
      overall assessment of the safe use of this material and all AAASAE in fragrances.

PMID- 22414648
TI  - Fragrance material review on 2-phenoxyethyl isobutyrate.
AB  - A toxicologic and dermatologic review of 2-phenoxyethyl isobutyrate when used as
      a fragrance ingredient is presented. 2-Phenoxyethyl isobutyrate is a member of
      the fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE).
      The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol
      with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate,
      acetate, propionate, butyrate, isobutyrate and carbonate esters. This review
      contains a detailed summary of all available toxicology and dermatology papers
      that are related to this individual fragrance ingredient and is not intended as a
      stand-alone document. Available data for 2-phenoxyethyl isobutyrate were
      evaluated, then summarized, and includes: physical properties, acute toxicity,
      skin irritation, mucous membrane (eye) irritation, skin sensitization,
      toxicokinetics, repeated dose, and genotoxicity data. A safety assessment of the
      entire AAASAE will be published simultaneously with this document. Please refer
      to Belsito et al. (2012) for an overall assessment of the safe use of this
      material and all AAASAE in fragrances.

PMID- 22414650
TI  - Fragrance material review on anisyl formate.
AB  - A toxicologic and dermatologic review of anisyl formate when used as a fragrance
      ingredient is presented. Anisyl formate is a member of the fragrance structural
      group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The AAASAE fragrance
      ingredients are prepared by reacting an aryl alkyl alcohol with a simple
      carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate, and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for anisyl formate were evaluated, then
      summarized, and includes: physical properties, acute toxicity, skin irritation,
      and skin sensitization data. A safety assessment of the entire AAASAE will be
      published simultaneously with this document. Please refer to Belsito et al.
      (2012) for an overall assessment of the safe use of this material and all AAASAE
      in fragrances.

PMID- 22414649
TI  - Capsaicin consumption, Helicobacter pylori CagA status and IL1B-31C>T genotypes:
      a host and environment interaction in gastric cancer.
AB  - Gastric cancer (GC) has been associated with a complex combination of genetic and
      environmental factors. In contrast to most countries, available information on GC
      mortality trends showed a gradual increase in Mexico. Our aim was to explore
      potential interactions among dietary (chili pepper consumption), infectious
      (Helicobacter pylori) and genetic factors (IL1B-31 genotypes) on GC risk. The
      study was performed in three areas of Mexico, with different GC mortality rates.
      We included 158 GC patients and 317 clinical controls. Consumption of capsaicin
      (Cap), the pungent active substance of chili peppers, was estimated by food
      frequency questionnaire. H. pylori CagA status was assessed by ELISA, and IL1B-31
      genotypes were determined by TaqMan assays and Pyrosequencing in DNA samples.
      Multivariate unconditional logistic regression was used to estimate potential
      interactions. Moderate to high Cap consumption synergistically increased GC risk
      in genetically susceptible individuals (IL1B-31C allele carriers) infected with
      the more virulent H. pylori (CagA+) strains. The combined presence of these
      factors might explain the absence of a decreasing trend for GC in Mexico.
      However, further research on gene-environment interactions is required to fully
      understand the factors determining GC patterns in susceptible populations, with
      the aim of recommending preventive measures for high risk individuals.

PMID- 22414651
TI  - Fragrance material review on 3-phenylpropyl acetate.
AB  - A toxicologic and dermatologic review of 3-phenylpropyl acetate when used as a
      fragrance ingredient is presented. 3-Phenylpropyl acetate is a member of the
      fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The
      AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with
      a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for 3-phenylpropyl acetate were evaluated, then
      summarized, and includes: physical properties, acute toxicity, skin irritation,
      skin sensitization, and toxicokinetics data. A safety assessment of the entire
      AAASAE will be published simultaneously with this document. Please refer to
      Belsito et al., 2012 for an overall assessment of the safe use of this material
      and all AAASAE in fragrances.

PMID- 22414652
TI  - Fragrance material review on 2-(p-tolyloxy)ethyl acetate.
AB  - A toxicologic and dermatologic review of 2-(p-tolyloxy)ethyl acetate when used as
      a fragrance ingredient is presented. 2-(p-tolyloxy)ethyl acetate is a member of
      the fragrance structural group aryl alkyl alcohol simple acid esters (AAASAE).
      The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol
      with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate,
      acetate, propionate, butyrate, isobutyrate and carbonate esters. This review
      contains a detailed summary of all available toxicology and dermatology papers
      that are related to this individual fragrance ingredient and is not intended as a
      stand-alone document. Available data for 2-(p-tolyloxy)ethyl acetate were
      evaluated, then summarized, and includes physical properties data. A safety
      assessment of the entire AAASAE will be published simultaneously with this
      document. Please refer to Belsito et al. (2012) for an overall assessment of the
      safe use of this material and all AAASAE in fragrances.

PMID- 22414653
TI  - Fragrance material review on 2-phenoxyethyl propionate.
AB  - A toxicologic and dermatologic review of 2-phenoxyethyl propionate when used as a
      fragrance ingredient is presented. 2-Phenoxyethyl propionate is a member of the
      fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The
      AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with
      a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for 2-phenoxyethyl propionate were evaluated, then
      summarized, and includes: physical properties, acute toxicity, skin irritation,
      skin sensitization, and genotoxicity data. A safety assessment of the entire
      AAASAE will be published simultaneously with this document. Please refer to
      Belsito et al. (2012) for an overall assessment of the safe use of this material
      and all AAASAE in fragrances.

PMID- 22414654
TI  - Fragrance material review on anisyl acetate.
AB  - A toxicologic and dermatologic review of anisyl acetate when used as a fragrance
      ingredient is presented. Anisyl acetate is a member of the fragrance structural
      group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The AAASAE fragrance
      ingredients are prepared by reacting an aryl alkyl alcohol with a simple
      carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for anisyl acetate were evaluated, then
      summarized, and includes: physical properties, skin irritation, skin
      sensitization, elicitation, and phototoxicity data. A safety assessment of the
      entire AAASAE will be published simultaneously with this document. Please refer
      to Belsito et al., 2012 for an overall assessment of the safe use of this
      material and all AAASAE in fragrances.

PMID- 22414655
TI  - Modulation of irinotecan-induced genomic DNA damage by theanine.
AB  - The possible chemoprotective activity of theanine against irinotecan-induced
      genomic DNA damage towards mouse bone marrow cells was investigated. Chromosomal
      aberrations, DNA damage, micronuclei formation and mitotic activity were studied
      in the current study as markers of genomic damage. Oxidative DNA stress markers
      such as 8-hydroxydeoxyguanosine, lipid peroxidation, reduced and oxidized
      glutathione levels were assessed as a possible mechanism underlying this
      amelioration. Theanine was neither genotoxic nor cytotoxic in mice at doses
      equivalent to 30 or 60 mg/kg for 12 days. Pretreatment of mice with theanine
      significantly reduced irinotecan-induced genomic damage in the bone marrow cells
      and these effects were dose dependent. Irinotecan induced marked biochemical
      alterations characteristic of oxidative DNA stress, including increased 8
      hydroxydeoxyguanosine, enhanced lipid peroxidation and reduction in the
      reduced/oxidized glutathione ratio. Prior administration of theanine ahead of
      irinotecan challenge ameliorated these oxidative DNA stress markers. Overall,
      this study provides for the first time that theanine has a protective role in the
      abatement of irinotecan-induced genomic damage in the bone marrow cells of mice
      that resides, at least in part, on its ability to modulate the cellular
      antioxidant levels and consequently protect bone marrow from irinotecan
      genotoxicity.

PMID- 22414656
TI  - Fragrance material review on 2-hydroxy-2-phenylethyl acetate.
AB  - A toxicologic and dermatologic review of 2-hydroxy-2-phenylethyl acetate when
      used as a fragrance ingredient is presented. 2-Hydroxy-2-phenylethyl acetate is a
      member of the fragrance structural group aryl alkyl alcohol simple acid esters
      (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl
      alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate
      formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This
      review contains a detailed summary of all available toxicology and dermatology
      papers that are related to this individual fragrance ingredient and is not
      intended as a stand-alone document. Available data for 2-hydroxy-2-phenylethyl
      acetate was evaluated then summarized and includes physical properties data. A
      safety assessment of the entire AAASAE will be published simultaneously with this
      document. Please refer to Belsito et al. (2012) for an overall assessment of the
      safe use of this material and all AAASAE in fragrances.

PMID- 22414657
TI  - Parenting and the emotional and behavioural adjustment of young children in
      families with a parent with bipolar disorder.
AB  - BACKGROUND: Children of parents with bipolar disorder are at increased risk of
      disturbance. AIMS: This study examined relationships between parental mood,
      parenting, household organization and child emotional and behavioural adjustment
      in families with a parent with bipolar disorder to determine areas of specific
      need for parenting support. METHOD: 48 parents were recruited through
      advertisements via self-help organizations. The study was conducted online.
      Parental mood and activity was assessed by self-report questionnaires (CES-D,
      ISS, MDQ and SRM); parenting was assessed using the Parenting Scale (PS). The SDQ
      was used to assess the parent's view of their child's emotional and behavioural
      difficulties. The Confusion, Hubbub and Order Scale (CHAOS) assessed household
      organization. RESULTS: Parents reported high levels of difficulties across all
      measures and scores were above clinical cut-offs on most scales. Children were
      reported as showing high levels of disturbance on the SDQ, including all sub
      scales. Parenting and depression scores were significantly positively correlated,
      as were depression, parenting and CHAOS score. Regression analyses indicated that
      CHAOS was the strongest predictor of Total Difficulties and Emotional Symptoms on
      the SDQ. CONCLUSIONS: Families are likely to benefit from interventions tailored
      to meet their parenting needs.

PMID- 22414658
TI  - Medial lemniscus lesion in pediatric hemiplegic patients without corticospinal
      tract and posterior thalamic radiation lesion.
AB  - OBJECTIVES: Using diffusion tensor imaging (DTI), we investigated the state of
      medial lemniscus (ML), corticospinal tract (CST), and posterior thalamic
      radiation (PTR), which were expected as probable reasons for clinical hemiplegia
      in pediatric patients, especially those who showed impaired fine motor control
      and proprioception, but no definite motor weakness or spasticity. METHODS: We
      recruited 13 hemiplegic patients and 8 age-matched healthy control subjects.
      Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) for the
      bilateral ML, CST, and PTR were calculated and compared between the affected
      hemisphere of the patient (AP), the unaffected hemisphere of the patient (UP),
      and the mean value of the bilateral hemispheres in control subjects (MC).
      RESULTS: FA and ADC values for the CST and PTR did not differ significantly
      between the AP, UP, and MC subgroups (p > 0.05). However, the FA value for the ML
      in AP showed a significant decrease, compared with that in UP (p = 0.012) and MC
      (p = 0.047). DTT for the CST and PTR showed preserved integrity and ML in the UP
      also had continuity to the cortex; however, ML in AP showed disruption.
      CONCLUSIONS: Using DTI, we demonstrated that the ML lesion might be related to
      clinical hemiplegia in pediatric patients.

PMID- 22414659
TI  - A pilot study on the validity of using pictures and videos for individualized
      symptom provocation in obsessive-compulsive disorder.
AB  - Distressing symptom-related anxiety is difficult to study in obsessive-compulsive
      disorder (OCD) due to the disorder's heterogeneity. Our aim was to develop and
      validate a set of pictures and films comprising a variety of prominent OCD
      triggers that can be used for individually tailored symptom provocation in
      experimental studies. In a two-staged production procedure a large pool of OCD
      triggers and neutral contents was produced and preselected by three
      psychotherapists specialized in OCD. A sample of 13 OCD patients and 13 controls
      rated their anxiety, aversiveness and arousal during exposure to OCD-relevant,
      aversive and neutral control stimuli. Our findings demonstrate differences
      between the responses of patients and controls to OCD triggers only. Symptom
      related anxiety was stronger in response to dynamic compared with static OCD
      relevant stimuli. Due to the small number of 13 patients included in the study,
      only tentative conclusions can be drawn and this study merely provides a first
      step of validation. These standardized sets constitute valuable tools that can be
      used in experimental studies on the brain correlates of OCD symptoms and for the
      study of therapeutic interventions in order to contribute to future developments
      in the field.

PMID- 22414660
TI  - Depersonalization disorder and anxiety: a special relationship?
AB  - A significant association between anxiety and depersonalization has been found in
      healthy controls and psychiatric patients irrespective of underlying conditions.
      Although patients with depersonalization disorder (DPD) often have a history of
      severe anxiety symptoms, clinical observations suggest that the relation between
      anxiety and depersonalization is complex and poorly understood. Using relevant
      rating scales, levels of anxiety and depersonalization were assessed in 291
      consecutive DPD cases. 'High' and 'low' depersonalization groups, were compared
      according to anxiety severity. Correlation and multivariate regression analyses
      were also used to assessed the contribution of anxiety to the phenomenology and
      natural course of depersonalization. A low but significant association between
      depersonalization and anxiety (as measured by Beck's Anxiety Inventory) was only
      apparent in those patients with low intensity depersonalization, but not in those
      with severe depersonalization. Levels of anxiety did not seem to make specific
      contributions to the clinical features of depersonalization itself, although DPD
      patients with high anxiety seem characterised by additional non-specific
      perceptual symptoms. The presence of a 'statistical dissociation' between
      depersonalization and anxiety adds further evidence in favour of
      depersonalization disorder being an independent condition and suggests that its
      association with anxiety has been overemphasized.

PMID- 22414661
TI  - Investigating association of four gene regions (GABRB3, MAOB, PAH, and SLC6A4)
      with five symptoms in schizophrenia.
AB  - Recently, microsatellite polymorphisms have been reported to be associated with
      four genes, GABRB3, MAOB, PAH, and SLC6A4, and their relationships have been
      tested to five symptom factors: hallucinations, delusions, negative symptoms,
      mania, and depression. These factors were frequently present in schizophrenia
      spectrum disorders in the Irish Study of High Density Schizophrenia Families
      (ISHDSF) with a proband with the diagnosis of schizophrenia (Bergen et al.,
      2009). Of these, GABRB3 and PAH were reported to be significantly associated with
      hallucinations and delusions in a 90-family subset of the ISHDSF, respectively.
      In this study, we tested the association of genetic markers from these four gene
      regions with the approximate five clinical symptoms, based upon 256 schizophrenia
      patients, with genotypic data obtained by higher resolution single nucleotide
      polymorphism (SNP) genotyping. We found one GABRB3 SNP (rs1426891, 70.8kb
      downstream of this gene) and haplotype constructed by three SNPs (rs1426891,
      rs2912602, and rs2912600) were significantly associated with hallucinations in
      Caucasians after Bonferroni correction for multiple testing (Bonferroni corrected
      P: 0.032 and 0.016, respectively). Additionally, we found one haplotype
      constructed by two SNPs, rs5905587-rs37615860, in MAOB/NDP gene region was
      significantly associated with delusions in all samples tested (Bonferroni
      corrected P: 0.048). These results provide additional evidence that GABRB3 and
      MAOB/NDP gene regions might constitute risk factors for hallucinations and
      delusions in schizophrenia.

PMID- 22414662
TI  - Emotional hyperreactivity as a core dimension of manic and mixed states.
AB  - Despite its obvious importance in mood disorders, characterization of emotional
      reactivity has been neglected in bipolar disorders. Concerning manic states and
      the current classification, the main criterion is the presence of an elevated or
      expansive mood. In contrast to this characteristic and often prolonged mood
      state, emotional reactivity refers to a brief evoked response to salient
      emotional stimuli. The goal of this study was to assess the intensity of
      emotional responses triggered by viewing slides in bipolar patients with manic or
      mixed states. Our hypothesis was that all emotional responses are exacerbated,
      whatever the valence of the stimuli. We compared 33 patients with manic or mixed
      states with 33 matched euthymic patients and 33 healthy control subjects. Arousal
      and attribution of valence were assessed while subjects viewed slides taken from
      the International Affective Picture System (positive, neutral and negative
      slides). Patients with manic or mixed states reported a higher arousal when
      viewing all types of slides in comparison with the other groups. Concerning
      attribution of valence, patients with manic or mixed states assessed neutral
      slides as more pleasant. When bipolar patients with manic and mixed states are
      placed in front of positive, neutral and negative slides, the slides trigger a
      higher intensity of emotions, whatever the valence of the emotional stimuli.
      These results strengthen the importance of emotional hyperreactivity as a core
      dimension in manic and mixed states in bipolar disorder.

PMID- 22414663
TI  - Association between catechol-O-methyltransferase Val158Met polymorphism and
      negative symptoms of schizophrenia in the Korean population.

PMID- 22414664
TI  - Role of Slr1045 in environmental stress tolerance and lipid transport in the
      cyanobacterium Synechocystis sp. PCC6803.
AB  - ATP-binding cassette (ABC) transporter proteins mediate energy-dependent
      transport of substrates across cell membranes. Numerous ABC transporter-related
      genes have been found in the Synechocystis sp. PCC6803 genome by genome sequence
      analysis including H(+), iron, phosphate, polysaccharide, and CO(2) transport
      related genes. The substrates of many other ABC transporters are still unknown.
      To identify ABC transporters involved in acid tolerance, deletion mutants of ABC
      transporter genes with unknown substrates were screened for acid stress
      sensitivities in low pH medium. It was found that cells expressing the deletion
      mutant of slr1045 were more sensitive to acid stress than the wild-type cells.
      Moreover, slr1045 expression in the wild-type cells was increased under acid
      stress. These results indicate that slr1045 is an essential gene for survival
      under acid stress. The mutant displayed high osmotic stress resistance and
      high/low temperature stress sensitivity. Considering the temperature-sensitive
      phenotype and homology to the organic solvent-resistant ABC system, we
      subsequently compared the lipid profiles of slr1045 mutant and wild-type cells by
      thin-layer chromatography. In acid stress conditions, the phosphatidylglycerol
      (PG) content in the slr1045 mutant cells was approximately 40% of that in the
      wild-type cells. Moreover, the addition of PG to the medium compensated for the
      growth deficiency of the slr1045 mutant cells under acid stress conditions. These
      data suggest that slr1045 plays a role in the stabilization of cell membranes in
      challenging environmental conditions. This article is part of a Special Issue
      entitled: Photosynthesis Research for Sustainability: from Natural to Artificial.

PMID- 22414665
TI  - Complex effects of 17beta-estradiol on mitochondrial function.
AB  - Existing literature on estradiol indicates that it affects mitochondrial
      functions at low micromolar concentrations. Particularly blockade of the
      permeability transition pore (PTP) or modulation of the enzymatic activity of one
      or more complexes of the respiratory chain were suspicious. We prepared
      mitoplasts from rat liver mitochondria (RLM) to study by single-channel patch
      clamp techniques the PTP, and from rat astrocytes to study the potassium BK
      channel said to modulate the PTP. Additionally, we measured respiration of intact
      RLM. After application of 17beta-estradiol (betaE) our single-channel results
      reveal a transient increase of activity of both, the BK-channel and the PTP
      followed by their powerful inhibition. Respiration measurements demonstrate
      inhibition of the Ca(2+)-induced permeability transition, as well, though only at
      higher concentrations (>=30MUM). At lower concentrations, we observed an increase
      of endogenous- and state 2-respiration. Furthermore, we show that betaE
      diminishes the phosphorylating respiration supported by complex I-substrates
      (glutamate/malate) or by the complex II-substrate succinate. Taken together the
      results suggest that betaE affects mitochondria by several modes, including
      partial inhibition of the activities of ion channels of the inner membrane and of
      respiration. This article is part of a Special Issue entitled: 17th European
      Bioenergetics Conference (EBEC 2012).

PMID- 22414666
TI  - Solution structure of CyanoP from Synechocystis sp. PCC 6803: new insights on the
      structural basis for functional specialization amongst PsbP family proteins.
AB  - The structure of the CyanoP subunit of photosystem II from the cyanobacterium
      Synechocystis sp. PCC 6803 has been determined in solution by Nuclear Magnetic
      Resonance spectroscopy. Combined with homology modeling of PsbP-like structures
      we have identified distinct structural differences between PsbP homologues which
      may account for the functional differences apparent between members of this
      protein family. A surface cleft containing a large number of conserved residues
      found only in CyanoP and PsbP-like homologues has been identified and our
      findings suggest that one of the potential cation binding sites found in CyanoP
      may be functionally significant. Evidence for the evolution and divergence of the
      PsbP super family is presented from a structural perspective including
      identification of residues which distinguish the PsbP family from unrelated
      proteins with a similar domain fold. This article is part of a Special Issue
      entitled: Photosynthesis Research for Sustainability: from Natural to Artificial.

PMID- 22414667
TI  - [A neonate with acute swelling of hands and feet].
AB  - A 4-week-old girl presented with acute swelling of hands and feet preceded by a
      red facial rash. In the days before formula feeding was gradually introduced.
      This proved to be a rare but severe generalized allergic reaction to cow milk.

PMID- 22414668
TI  - [A patient with bilateral testicular cancer].
AB  - BACKGROUND: In men aged 15-34 testicular cancer is the most commonly occurring
      malignancy. After treatment, the average 5-year survival rate is 85%. Recurring
      symptoms or raised tumour markers may indicate the presence of a second primary
      contralateral testicular tumour. CASE DESCRIPTION: A 34-year-old man presented
      with pain in his left testicle. Eight years previously he had been diagnosed with
      cancer of his right testicle which was treated successfully by orchidectomy and
      two cycles of chemotherapy. Further investigations revealed raised tumour
      markers. The patient proved to have a contralateral testis carcinoma with 2 lung
      metastases. CONCLUSION: 1-3% of patients with testicular cancer develop
      metachronous (i.e. not concurrent) contralateral testicular cancer. Follow-up and
      self-examination are very important for early diagnosis of a metachronous
      contralateral malignancy.

PMID- 22414669
TI  - [Suspicion of pulmonary embolism: added value of CT depends on patient
      characteristics and referring individual].
AB  - OBJECTIVE: To evaluate the added value of CT pulmonary angiography (CTPA) in
      patients who have undergone this procedure for suspected pulmonary embolism (PE).
      We evaluated this added value by investigating both the rate of pulmonary
      embolism ascertained and the rate of CTPA without abnormal findings, each in
      relationship to various characteristics of the patient and referring individuals.
      DESIGN: Diagnostic cross sectional research METHOD: Data on all patients 18 years
      and older who underwent CTPA from November 2008 to February 2011 at the Leiden
      University Medical Centre because of suspected pulmonary embolism were entered
      into a database. We collected information on the patient, referring individual,
      reason for referral and the outcome of the CTPA, and described the rate of
      positive CTPA for various subgroups. In addition, we described the rate of CTPA's
      within these groups in which no abnormalities were demonstrable. RESULTS: After
      exclusion of patients with a PE found by chance (n = 28), the total patient
      population was comprised of 1344 patients. In 19.1% of these patients, PE was
      confirmed by CTPA. This percentage was lower in the female population (16.9%; 95%
      CI: 14.4-19.6), and in outpatients (10.9%; 95% CI: 5.5-16.3). In 42% of CTPAs in
      the group of patients younger than 40 years,  no abnormalities were found
      CONCLUSION: The CTPA yield could be improved in women and younger patients. This
      would increase cost-effectiveness and reduce unnecessary side effects.  For this
      reason, further investigation into the motives of doctors referring young people,
      women and outpatients would be helpful in preventing the overuse of this
      diagnostic tool.

PMID- 22414670
TI  - [Clinical problems in multiple osteochondroma].
AB  - Multiple osteochondroma, also known as hereditary multiple exostoses, is a
      relatively rare genetic disorder characterized by the presence of multiple
      osteochondromas. The disease is frequently painful, with restriction of the
      activities of daily living, problems with carrying out an occupation and
      performance at school. In addition, characteristic skeletal deformities and
      postural abnormalities of the joints very frequently occur in patients with this
      disorder. Malignant transformation of osteochondroma to chondrosarcoma occurs in
      1-5% of the patients with multiple osteochondroma. Treatment of patients with
      multiple osteochondromas must be tuned to the problems experienced by the
      patient. Symptomatic osteochondromas are often an indication for excision;
      knowledge of the natural progression of the abnormality is important in this.
      Periodical screening is essential: in children to prevent or correct deformity
      and postural abnormalities and in adults to detect and treat malignant
      transformation of osteochondroma at an early stage.

PMID- 22414671
TI  - [Intraoperative imaging using fluorescence].
AB  - Intraoperative imaging using fluorescence is an experimental technique by which
      specific tissue structures can be visualised. A preoperatively administered
      optical contrast agent with fluorescence properties is detected during the
      operation using a light-sensitive camera system. Using this technique, vital
      anatomical structures such as blood vessels, bile ducts and ureters are rendered
      visible to the surgeon. The technique can also serve as a detection method for
      sentinel lymph nodes. Furthermore, tumour-specific fluorescent tracers are being
      developed to delineate tumours from surrounding tissue. The aim of this is to
      increase the number of radical cancer operations and reduce iatrogenic tissue
      damage. Currently, clinical studies are being conducted to investigate the value
      and feasibility of this technique for different surgical specialties.

PMID- 22414672
TI  - [Abdominal pain with a microvascular cause].
AB  - A 50-year-old Caucasian man was admitted with unexplained abdominal pain. Based
      on CT scan results, a perforation resulting from colitis of the transverse colon
      was suspected. Additional colonoscopy showed ulcerative stenosis of the
      transverse colon. Initially, the patient recovered on conservative treatment;
      however, because of persistent stenosis, an elective resection of the transverse
      colon was performed. A CT scan revealed free gas around the anastomosis on the
      fourth postoperative day. Relaparotomy revealed leakage and diffuse ischaemic
      changes around the anastomosis as well as perforations at different sites on the
      small bowel. Postoperative CT angiography showed stenosis of the proximal celiac
      trunk, which was successfully stented. Digital subtraction angiography (DSA)
      revealed luminal irregularities of the superior mesenteric, the middle colic as
      well as the main hepatic and splenic arteries. Eventually, the clinical
      presentation and surgical, radiologic and histopathological findings together led
      to the diagnosis of polyarteritis nodosa (PAN). Aggressive treatment with
      glucocorticoids and cyclophosphamide resulted in the resolution of symptoms and
      the disappearance of radiologic abnormalities.

PMID- 22414673
TI  - [CTPA in suspected pulmonary embolism: diagnostic strategy].
AB  - De Bruin and colleagues recently analysed the performance of the CTPA scan in
      patients with suspected pulmonary embolism. Their study shows that in a
      significant number of patients no abnormalities were found on a CTPA scan, a
      troubling finding given the radiation exposure. Young patients and ambulatory
      patients, in particular, often had a completely normal CTPA scan. Better
      stratification of patients with a high suspicion of pulmonary embolism is
      required, including evaluation of the value of clinical decision rules in
      ambulatory patients with suspected pulmonary embolism. In addition, the use of
      perfusion scanning, which involves significantly less radiation exposure,
      deserves further research in young people. Principally, a diagnostic strategy for
      pulmonary embolism comprising a clinical decision rule, followed by a D-dimer
      test if necessary, should be applied in clinical practice. This strategy will
      significantly reduce the number of CTPA scans showing no pulmonary embolism.

PMID- 22414674
TI  - Endogenous endomorphin-2 contributes to spinal K-opioid antinociception.
AB  - BACKGROUND/AIMS: Multiple opioid receptor (OR) types and endogenous opioid
      peptides exist in the spinal dorsal horn and there may be interactions among
      these receptor types that involve opioid peptides. In a previous study we
      observed that antinociceptive effects of the selective kappa-opioid receptor
      (kappaOR) agonist, U50,488H, was attenuated in MU-opioid receptor (MUOR) knockout
      mice as compared to wild-type mice when administered spinally. This suggests that
      an interaction between kappaORs and MUORs exits in the spinal cord. The present
      study was aimed at investigating whether endogenous opioid peptides were involved
      in such interaction. METHODS: We examined whether the presence of antibodies to
      endogenous opioid peptides, endomorphin-2, met-enkephalin and dynorphin A
      affected the antinociceptive effects of spinal U50,488H in rats. The tail-flick
      test was used to assess pain thresholds. RESULTS: The increase in tail-flick
      latency after spinal U50,488H was attenuated when the rats were pretreated
      intrathecally with antiserum against endomorphin-2. Pretreatments with antisera
      against met-enkephalin and dynorphin A had no effect on U50,488H antinociception.
      The antisera alone did not affect pain threshold. CONCLUSION: The results suggest
      that endomorphin-2, an endogenous opioid peptide highly selective to the MUOR,
      plays a role in antinociception induced by kappaOR activation in the spinal cord.

PMID- 22414675
TI  - Insulin-like growth factor-1, insulin-like growth factor binding protein-3 and
      lobule type in the Nurses' Health Study II.
AB  - INTRODUCTION: Previous research in the Nurses' Health Study (NHS) and the NHSII
      observed that, among women diagnosed with benign breast disease (BBD), those with
      predominant type 1/no type 3 lobules (a marker of complete involution) versus
      other lobule types were at lower risk of subsequent breast cancer. Studies in
      animal models suggest that insulin-like growth factor-1 (IGF-1) may inhibit
      involution of lobules in the breast; however, this has not been studied in
      humans. METHODS: We conducted a cross-sectional study among 472 women in the
      NHSII who were diagnosed with biopsy-confirmed proliferative BBD between 1991 and
      2002 and provided blood samples between 1996 and 1999. A pathologist, blinded to
      exposure status, classified lobule type in normal adjacent tissue on available
      biopsy slides according to the number of acini per lobule. For each participant,
      the pathologist determined the predominant lobule type (that is, type 1, type 2,
      or type 3) and whether any type 1 or any type 3 lobules were present. Lobule type
      was then classified as: predominant type 1/no type 3 lobules, which is suggestive
      of complete involution; or other lobule types. Multivariate logistic models were
      used to assess the associations between plasma IGF-1, insulin-like growth factor
      binding protein-3 (IGFBP-3), and the ratio of IGF-1:IGFBP-3 levels with lobule
      type. RESULTS: In univariate analyses, greater age, higher body mass index,
      postmenopausal status, nulliparity, and lower IGF-1 levels were associated with
      predominant type 1/no type 3 lobules (P < 0.05). In multivariate models adjusting
      for age and assay batch, higher IGF-1 levels were associated with decreased odds
      of predominant type 1/no type 3 lobules (odds ratio quartile 4 vs. quartile 1 =
      0.37, 95% confidence interval = 0.15 to 0.89). Greater ratios of IGF-1:IGFBP-3
      levels were also associated with decreased odds of predominant type 1/no type 3
      lobules (odds ratio quartile 4 vs. quartile 1 = 0.26, 95% confidence interval =
      0.11 to 0.64). These results were slightly attenuated after adjustment for other
      potential predictors of lobule type. CONCLUSIONS: Higher IGF-1 levels and a
      greater IGF-1:IGFBP-3 ratio were associated with decreased odds of having
      predominant type 1 lobules/no type 3 lobules among women with proliferative BBD
      in the NHSII. This study provides further evidence for the role of insulin-like
      growth factors in the structure of breast lobules and lobular involution.

PMID- 22414676
TI  - The neuropsychological profile of children, adolescents, and young adults with
      anorexia nervosa.
AB  - The neuropsychological profile of a sample of 155 patients with a clinical
      diagnosis of anorexia nervosa was assessed using a test battery specifically
      developed for such patients. The current findings suggest that the patients
      display a common neuropsychological profile including both strengths and
      weaknesses when compared with published norms. The patients displayed good verbal
      fluency skills, but performed poorly on tests of visuospatial memory, associated
      with relatively weak central coherence. They were within the average range on the
      assessment of executive functioning except for one measure of set-shifting. This
      study provides a valuable point of reference for clinicians when considering
      treatment options.

PMID- 22414677
TI  - Differential impairment of source memory in progressive versus non-progressive
      behavioral variant frontotemporal dementia.
AB  - Episodic memory has recently been shown to be impaired in the behavioral variant
      of frontotemporal dementia (bvFTD) when so-called non-progressive cases are
      excluded. Such non-progressive cases present with the behavioral features of
      bvFTD, but show no evidence of cognitive decline over time. To date, evidence
      regarding episodic memory performance in bvFTD subgroups on more stringent tasks
      is lacking. We investigated temporal and spatial source memory in progressive (n
      = 7) versus non-progressive (n = 12) bvFTD. BvFTD cases were retrospectively
      classified based on general cognitive decline on the Addenbrooke's Cognitive
      Examination Revised, and the presence of atrophy on structural neuroimaging, over
      3 years following diagnosis. Progressors showed impaired temporal and spatial
      source retrieval. Non-progressors displayed temporal source deficits only. These
      differential source memory profiles point to the variability of episodic memory
      performance in bvFTD, and underscore the importance of differential diagnosis of
      bvFTD subgroups using longitudinal and neuroimaging data.

PMID- 22414678
TI  - PENS syndrome: a new neurocutaneous phenotype.
AB  - BACKGROUND: The central nervous system originates ontogenetically from the
      ectoderm and therefore numerous neurocutaneous syndromes exist. OBJECTIVE: We
      describe a novel neurocutaneous syndrome with characteristic epidermal papules
      and plaques associated with mild psychomotor retardation and epilepsy with a good
      prognosis. METHODS: We investigated history, clinical features, laboratory
      parameters including karyotype, histopathological and immunohistological
      examination, electron microscopy, HPV infection, EEG and neurologic imaging in
      patients with an unusual symptom complex. RESULTS: Six children are reported with
      characteristic keratotic papules and plaques of 'gem-like' appearance, randomly
      distributed on the trunk and the proximal part of the limbs. Four patients were
      unrelated and two were siblings. The cutaneous lesions appeared congenitally or
      developed soon after birth. The skin lesions were rounded or of an irregularly
      polycyclic shape, ranging from 0.5 to 1.5 cm in diameter. A few to eighteen
      lesions were present. The lesional surface was rough and of white or yellowish
      color. Histopathological examination showed acanthokeratosis, but immunostaining
      for keratins and melanocytes, electron microscopy and laboratory results were
      within normal range. During the natural course of the disease the lesions were
      stable and asymptomatic. All but one of our six patients developed neurologic
      signs and symptoms during the first year of life, in the form of epilepsy and
      psychomotor delay. Five children had low intellectual performance together with
      EEG abnormalities and some had MRI changes of the brain. One patient had marked
      language impairment. The central nervous system involvement had a peculiar benign
      and self-limiting course and total normalization occurred in one case.
      LIMITATIONS: We present only a small series of patients. CONCLUSION: Cutaneous
      lesions showing identical clinical and microscopical features, but without any
      extracutaneous abnormalities, have recently been described by Torrelo et al. [J
      Am Acad Dermatol 2011;64:888-892] under the designation 'papular epidermal nevus
      with "skyline" basal cell layer (PENS)'. An association of such nevi with
      neurologic abnormalities had so far only been published in the 'Atlas of
      Genodermatoses' edited by Caputo and Tadini. We believe that this unique and
      otherwise undescribed symptom complex is a new neurocutaneous phenotype that may
      be called PENS syndrome. Whether this new syndrome can be categorized as a
      distinct phenotype within the group of epidermal nevus syndromes remains
      speculative and has to be clarified by further investigations.

PMID- 22414679
TI  - Synthesis and structure elucidation of novel fused 1,2,4-triazine derivatives as
      potent inhibitors targeting CYP1A1 activity.
AB  - Synthesis and structure elucidation of new series of novel fused 1,2,4-triazine
      derivatives 3a-3f, 4a-4i and 6a-6b and their inhibitory activities are presented.
      Molecular structures of the synthesized compounds were confirmed by (1)H NMR,
      (13)C NMR, MS spectra and elemental analyses. X-ray crystallographic analysis was
      performed on 2-acetyl-8-(N,N-diacetylamino)-6-(4-methoxybenzyl)-3-(4-methoxy
      phenyl)-7-oxo-2,3-dihydro-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazine 3d and 2
      acetyl-8-(N-acetylamino)-6-benzyl-3-(4-chlorophenyl)-3-methyl-7-oxo-2,3-dihydro
      7H-[1,2,4]triazolo[4,3-b][1,2,4]triazine 4e to secure their structures. The
      inhibitory effect of these compounds toward the CPY1A1 activity was screened to
      determine their potential as promising anticancer drugs. Our data showed that
      compounds 4e, 5a, 5b and 6b possess the highest inhibitory effects among all
      tested compounds. Furthermore, analysis of triazolotriazine derivatives docking
      showed that these compounds bind only at the interface of substrate recognition
      site 2 (SRS2) and (SRS6) at the outer surface of the protein. Amino-acids ASN214,
      SER216 and ILE462 participate in the binding of these compounds through H-bonds.

PMID- 22414680
TI  - Potential hazards to embryo implantation: A human endometrial in vitro model to
      identify unwanted antigestagenic actions of chemicals.
AB  - Embryo implantation is a crucial step in human reproduction and depends on the
      timely development of a receptive endometrium. The human endometrium is unique
      among adult tissues due to its dynamic alterations during each menstrual cycle.
      It hosts the implantation process which is governed by progesterone, whereas
      17beta-estradiol regulates the preceding proliferation of the endometrium. The
      receptors for both steroids are targets for drugs and endocrine disrupting
      chemicals. Chemicals with unwanted antigestagenic actions are potentially
      hazardous to embryo implantation since many pharmaceutical antiprogestins
      adversely affect endometrial receptivity. This risk can be addressed by human
      tissue-specific in vitro assays. As working basis we compiled data on chemicals
      interacting with the PR. In our experimental work, we developed a flexible in
      vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin
      compounds on pre-selected target genes were characterized by sigmoidal
      concentration-response curves obtained by RT-qPCR. The estrogen sulfotransferase
      (SULT1E1) was identified as the most responsive target gene by microarray
      analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration
      dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower
      potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl
      acetoacetate showed no effect. The effects of progesterone and RU486 were
      confirmed on the protein level by Western blotting. We demonstrated proof of
      principle that our Ishikawa model is suitable to study quantitatively effects of
      antiprogestin-like chemicals on endometrial target genes in comparison to
      pharmaceutical reference compounds. This test is useful for hazard identification
      and may contribute to reduce animal studies.

PMID- 22414681
TI  - Enteral vs total parenteral nutrition following major upper gastrointestinal
      surgery.
AB  - A best evidence topic in surgery was written according to a structured protocol.
      The question addressed was in patients undergoing elective major upper
      gastrointestinal surgery requiring post-operative nutritional support, does
      enteral feeding as compared to total parenteral feeding confer any clinical
      benefits. Thirty-two papers were identified by a search of the Medline and Embase
      databases, of which seven represented the best evidence to answer the clinical
      question. The authors, journal, date and country of publication, patient group,
      study group, relevant outcomes and results of these papers were tabulated. All
      seven of these papers were randomised controlled trials which demonstrated
      enteral nutrition to be associated with shorter hospital stay, lower incidence of
      severe or infectious complications, lower severity of complications and decreased
      cost as compared to parenteral nutrition. For patients undergoing elective major
      upper gastrointestinal surgery requiring post-operative nutritional support,
      enteral feeding should be considered as the most desirable form of post-operative
      feeding.

PMID- 22414682
TI  - The effects of epidermal growth factor and transforming growth factor-alpha on
      secretion of interleukin-8 and growth-regulated oncogene-alpha in human granulosa
      lutein cells.
AB  - BACKGROUND: In order to investigate the roles of epidermal growth factor (EGF)
      and transforming growth factor (TGF)-alpha in ovulation, we studied the
      production of interleukin (IL)-8 and growth-regulated oncogene (GRO)-alpha in
      cultured human granulosa-lutein cells. METHODS: Granulosa-lutein cells obtained
      from the follicular fluids of in vitro fertilization and embryo transfer patients
      were cultured and treated with EGF, TGF-alpha, tumor necrosis factor (TNF)-alpha
      or 12-O-tetradecanoylphorbol 13-acetate (TPA). An immortalized granulosa cell
      line (GC1a) was also cultured and treated with EGF, TGF-alpha or mitogen
      activated protein kinase kinase inhibitor. The supernatants were collected, and
      IL-8 and GRO-alpha were measured by ELISA. RESULTS: The levels of IL-8 and GRO
      alpha were significantly increased after treatment with EGF, TGF-alpha, TNF-alpha
      and TPA by primary cultured granulosa-lutein cells. The levels of IL-8 and GRO
      alpha were also significantly increased after treatment with EGF or TGF-alpha in
      a dose-dependent manner by GC1a. When GC1a was treated with EGF, TGF-alpha or
      U0126, the levels of IL-8 and GRO-alpha were significantly decreased. CONCLUSION:
      Our data indicate that the production of IL-8 and GRO-alpha is upregulated by EGF
      and TGF-alpha. It is suggested that EGF and TGF-alpha may play an important role
      in luteinization processes involving IL-8 and GRO-alpha production.

PMID- 22414683
TI  - A novel BCI based on ERP components sensitive to configural processing of human
      faces.
AB  - This study introduces a novel brain-computer interface (BCI) based on an oddball
      paradigm using stimuli of facial images with loss of configural face information
      (e.g., inversion of face). To the best of our knowledge, till now the configural
      processing of human faces has not been applied to BCI but widely studied in
      cognitive neuroscience research. Our experiments confirm that the face-sensitive
      event-related potential (ERP) components N170 and vertex positive potential (VPP)
      have reflected early structural encoding of faces and can be modulated by the
      configural processing of faces. With the proposed novel paradigm, we investigate
      the effects of ERP components N170, VPP and P300 on target detection for BCI. An
      eight-class BCI platform is developed to analyze ERPs and evaluate the target
      detection performance using linear discriminant analysis without complicated
      feature extraction processing. The online classification accuracy of 88.7% and
      information transfer rate of 38.7 bits min(-1) using stimuli of inverted faces
      with only single trial suggest that the proposed paradigm based on the configural
      processing of faces is very promising for visual stimuli-driven BCI applications.

PMID- 22414684
TI  - Completeness of infectious disease notification in the United Kingdom: A
      systematic review.
AB  - OBJECTIVES: Infectious disease legislation in the United Kingdom has recently
      changed. Our aim was to provide a baseline against which to assess the impact of
      these changes by synthesising current knowledge on completeness of notification
      and on factors associated with better reporting rates. METHODS: We systematically
      reviewed the literature for studies reporting completeness of reporting of
      notifiable infectious diseases in the United Kingdom over the past 35 years.
      RESULTS: Altogether, 46 studies met our search criteria. Reporting completeness
      varied from 3% to 95% and was most strongly correlated with the disease being
      reported. Median reporting completeness was 73% (range 6%-93%) for tuberculosis,
      65% (range 40%-95%) for meningococcal disease, and 40% (range 3%-87%) for other
      diseases (Kruskal-Wallis test, p < 0.05). Reporting completeness did not change
      for either tuberculosis or meningococcal disease over the period studied. In
      multivariate analysis, none of the factors examined (study size, study time
      period, number of data sources used to assess completeness, uncorrected or
      corrected study design) were significantly associated with reporting
      completeness. CONCLUSION: Reporting completeness has not improved over the past
      three decades. It remains sub-optimal even for diseases which are under enhanced
      surveillance or are of significant public health importance.

PMID- 22414685
TI  - Screening of healthcare workers in response to a group A streptococcal outbreak
      in a maternity setting.

PMID- 22414686
TI  - Action reflections: a client-centered technique to bridge the WHY-HOW transition
      in Motivational Interviewing.
AB  - BACKGROUND: When using Motivational Interviewing (MI), once resistance or
      ambivalence are resolved and motivation is solidified, many practitioners
      struggle with how best to transition the discussion toward action planning, while
      still retaining the spirit and style of client centeredness, i.e., moving from
      the WHY phase to the HOW phase of counseling in a style that is MI-consistent.
      For many, there is a perception that the counseling style, skills, and strategies
      used to build motivation are distinct from those used in the action planning
      phase. The WHY to HOW transition does not, however, necessitate abandoning a
      client-centered style for a more overtly educational or directive style. Goal
      setting, action planning, provision of advice, and relapse prevention can be
      implemented from an autonomy supportive, MI consistent framework. METHOD: To this
      end, this article will present a new class of reflection, which we have termed
      "action reflections", that can be used to help bridge the WHY-HOW gap. Action
      reflections (AR) allow the clinician to maintain a tone and orientation that are
      consistent with MI, i.e. autonomy support; guiding versus directing, during the
      action phase of counseling. They differ from reflecting change talk as they focus
      not on the WHY of change, but the HOW, WHEN, or WHERE. Action Reflections (ARs)
      also differ from the more common type of reflections such as those that focus on
      client feelings, rolling with resistance, or acknowledging ambivalence as ARs
      usually contain a potential concrete step that the client has directly or
      obliquely mentioned. Like any type of reflection, ARs represent the clinician's
      best guess for what the client has said or, more apropos here, where the
      conversation might be heading. CONCLUSION: This article describes the various
      types of ARs and provides examples of each to help clinicians incorporate them
      into their behavior change counseling.

PMID- 22414687
TI  - GLP1-derived nonapeptide GLP1(28-36)amide protects pancreatic beta-cells from
      glucolipotoxicity.
AB  - Type 2 diabetes, often associated with obesity, results from a deficiency of
      insulin production and action manifested in increased blood levels of glucose and
      lipids that further promote insulin resistance and impair insulin secretion.
      Glucolipotoxicity caused by elevated plasma glucose and lipid levels is a major
      cause of impaired glucose-stimulated insulin secretion from pancreatic beta
      cells, due to increased oxidative stress, and insulin resistance. Glucagon-like
      peptide-1 (GLP1), an insulinotropic glucoincretin hormone, is known to promote
      beta-cell survival via its actions on its G-protein-coupled receptor on beta
      cells. Here, we report that a nonapeptide, GLP1(28-36)amide, derived from the C
      terminal domain of the insulinotropic GLP1, exerts cytoprotective actions on INS
      1 beta-cells and on dispersed human islet cells in vitro in conditions of
      glucolipotoxicity and increased oxidative stress independently of the GLP1
      receptor. The nonapeptide appears to enter preferably stressed, glucolipotoxic
      cells compared with normal unstressed cells. It targets mitochondria and improves
      impaired mitochondrial membrane potential, increases cellular ATP levels,
      inhibits cytochrome c release, caspase activation, and apoptosis, and enhances
      the viability and survival of INS-1 beta-cells. We propose that GLP1(28-36)amide
      might be useful in alleviating beta-cell stress and might improve beta-cell
      functions and survival.

PMID- 22414688
TI  - Blood pressure-lowering effects of beetroot juice and novel beetroot-enriched
      bread products in normotensive male subjects.
AB  - A number of vegetables have a high nitrate content which after ingestion can be
      reduced to nitrite by oral bacteria, and further to vasoprotective NO
      endogenously. In the present study, two separate randomly controlled, single
      blind, cross-over, postprandial studies were performed in normotensive
      volunteers. Ambulatory blood pressure (BP) was measured over a 24 h period
      following consumption of either four doses of beetroot juice (BJ), 0, 100, 250
      and 500 g (n 18), or three bread products, control bread (0 g beetroot), red
      beetroot- and white beetroot-enriched breads (n 14). Total urinary
      nitrate/nitrite (NO(x)) was measured at baseline, and at 2, 4 and 24 h post
      ingestion. BJ consumption significantly, and in a near dose-dependent manner,
      lowered systolic BP (SBP, P < 0.01) and diastolic BP (DBP, P < 0.001) over a
      period of 24 h, compared with water control. Furthermore, bread products enriched
      with 100 g red or white beetroot lowered SBP and DBP over a period of 24 h (red
      beetroot-enriched bread, P <0.05), with no statistical differences between the
      varieties. Total urinary NO(x) significantly increased following the consumption
      of 100 g (P < 0.01), 250 g (P <0.001) and 500 g BJ (P <0.001) and after red
      beetroot-enriched bread ingestion (P <0.05), but did not reach significance for
      white beetroot-enriched bread compared with the no-beetroot condition. These
      studies demonstrated significant hypotensive effects of a low dose (100 g) of
      beetroot which was unaffected by processing or the presence of betacyanins. These
      data strengthen the evidence for cardioprotective BP-lowering effects of dietary
      nitrate-rich vegetables.

PMID- 22414689
TI  - Insights into substrate recognition by the Escherichia coli Orf135 protein
      through its solution structure.
AB  - Escherichia coli Orf135 hydrolyzes oxidatively damaged nucleotides such as 2
      hydroxy-dATP, 8-oxo-dGTP and 5-hydroxy-CTP, in addition to 5-methyl-dCTP, dCTP
      and CTP. Nucleotide pool sanitization by Orf135 is important since nucleotides
      are continually subjected to potential damage by reactive oxygen species produced
      during respiration. Orf135 is a member of the Nudix family of proteins which
      hydrolyze nucleoside diphosphate derivatives. Nudix hydrolases are characterized
      by the presence of a conserved motif, even though they recognize various
      substrates and possess a variety of substrate binding pockets. We investigated
      the tertiary structure of Orf135 and its interaction with a 2-hydroxy-dATP analog
      using NMR. We report on the solution structure of Orf135, which should contribute
      towards a structural understanding of Orf135 and its interaction with substrates.

PMID- 22414690
TI  - Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster.
AB  - The crystal structure of the NTF2-like domain of the Drosophila homolog of Ras
      GTPase SH3 Binding Protein (G3BP), Rasputin, was determined at 2.7A resolution.
      The overall structure is highly similar to nuclear transport factor 2: It is a
      homodimer comprised of a beta-sheet and three alpha-helices forming a cone-like
      shape. However, known binding sites for RanGDP and FxFG containing peptides show
      electrostatic and steric differences compared to nuclear transport factor 2. A
      HEPES molecule bound in the structure suggests a new, and possibly
      physiologically relevant, ligand binding site.

PMID- 22414691
TI  - L-type voltage-operated calcium channels, N-methyl-D-aspartate receptors and
      neuronal nitric-oxide synthase form a calcium/redox nano-transducer within lipid
      rafts.
AB  - Cytosolic calcium plays a leading role in the control of neuronal excitability,
      plasticity and survival. This work aims to experimentally assess the possibility
      that lipid rafts of the plasma membrane can provide a structural platform for a
      faster and tighter functional coupling between calcium and nitric-oxide signaling
      in neurons. Using primary cerebellar granule neurons (CGN) in culture this
      hypothesis has been experimentally assessed with fluorescence resonance energy
      transfer imaging, preparations of lipid rafts-enriched membrane fragments and
      western blotting. The results obtained in this work demonstrated that major
      calcium entry systems of the plasma membrane of CGN (L-type calcium channels and
      N-methyl-D-aspartate receptors) and nitric-oxide synthase are separated by less
      than 80 nm from each other within lipid rafts-associated sub-microdomains,
      suggesting a new role of lipid rafts as neuronal calcium/redox nano-transducers.

PMID- 22414692
TI  - Crystal structure and substrate-binding mode of a novel pectate lyase from
      alkaliphilic Bacillus sp. N16-5.
AB  - The pectate lyase (Bsp165PelA) from Bacillus sp. N16-5 has great potential in
      industrial applications because it shows high specific activity under extremely
      alkaline conditions. Besides, activity measurement of Bsp165PelA does not require
      addition of calcium, in a way different from the other pectate lyases. Here we
      report crystal structures of Bsp165PelA in apo-form and in complex with
      trigalacturonate. The parallel beta-helix, active site residues and substrate
      binding cleft are similar to those in the other pectate lyases from
      Polysaccharide Lyase family 1. However, some of the highly conserved Ca(2+)
      binding residues and secondary structures are altered in Bsp165PelA, making it
      difficult to coordinate with Ca(2+) as in the other pectate lyases. We found
      Bsp165PelA forms some direct enzyme-substrate interactions instead of using
      Ca(2+) ions bridging in the extremely alkaline environment.

PMID- 22414693
TI  - Measurement of hemoglobin in whole blood using a partial least squares regression
      model with selected second derivative near infrared transmission spectral
      signals.
AB  - In this work, we propose a signal selection procedure for determination of
      hemoglobin (Hb) concentration in whole blood using near infrared (NIR)
      transmission spectral signals. A dataset of 190 whole blood NIR transmission
      spectra with reference Hb concentrations was used to evaluate the method.
      Spectral signals were selected based on the squared correlation coefficient
      (R(2)) between the signal and the Hb concentration. An improved uninformative
      variable elimination (UVE) procedure was performed to remove redundant signals
      from the primary selected signal set. A partial least squares (PLS) regression
      model was built with the final selected signals and the corresponding Hb
      concentrations. The results indicate that the proposed method is effective at
      increasing the predictive power of the NIR-PLS spectral model for determining Hb
      concentration in whole blood samples.

PMID- 22414694
TI  - Rapamycin suppresses the recurrent excitatory circuits of dentate gyrus in a
      mouse model of temporal lobe epilepsy.
AB  - Recurrent excitatory circuits and abnormal recurrent excitatory inputs are
      essential in epileptogenesis. Studies in temporal lobe epilepsy have shown that
      mossy fiber sprouting, which represents synaptic reorganization, renders the
      formation of abnormal recurrent excitatory circuits and inputs. The mammalian
      target of rapamycin (mTOR) pathway has recently been proved important in mossy
      fiber sprouting. In the present study, rapamycin, a mTOR inhibiter, was injected
      into the mouse of temporal lobe epilepsy. Electrophysiological and histological
      properties of the hippocampus were investigated by whole cell patch clamp,
      extracellular recording and Timm staining. Following the development of epilepsy,
      frequency of spontaneous excitatory postsynaptic currents (EPSCs) and amplitude
      of antidromically evoked EPSCs in granule cells were remarkably increased, as
      well as the epileptiform activity and mossy fiber sprouting were detected, which
      indicated the formation of abnormal recurrent excitatory circuits. By the use of
      rapamycin, frequency of spontaneous EPSCs, amplitude of antidromically evoked
      EPSCs, the epileptiform activity and mossy fiber sprouting were all remarkably
      suppressed. Our findings suggested an anti-epileptogenic role of rapamycin by
      suppressing the recurrent excitatory circuits of dentate gyrus.

PMID- 22414695
TI  - KCC2 transport activity requires the highly conserved L675 in the C-terminal
      beta1 strand.
AB  - The activity of the neuron-specific K(+), Cl(-) co-transporter 2 (KCC2) is
      required for hyperpolarizing action of GABA and glycine. KCC2-mediated transport
      therefore plays a pivotal role in neuronal inhibition. Few analyses have
      addressed the amino acid requirements for transport-competent conformation. KCC2
      consists of 12 transmembrane domains flanked by two intracellular termini.
      Structural analyses of a related archaeal protein have identified an evolutionary
      extremely conserved beta1 strand, which links the transmembrane domain to a C
      terminal dimerization interface. Here, we focused on the sequence requirement of
      this linker. We mutated four highly conserved amino acids of the beta1 strand
      ((673)QLLV(676)) to alanine and analyzed the functional consequences in mammalian
      cells. Flux measurements demonstrated that L(675A) significantly reduced KCC2
      transport activity by 41%, whereas the other three mutants displayed normal
      activity. Immunocytochemistry and cell surface labeling revealed normal
      trafficking of all four mutants. Altogether, our results identify L(675) as a
      critical residue for KCC2 transport activity. Furthermore, in view of its
      evolutionary conservation, the data suggest a remarkable tolerance of the KCC2
      transport activity to amino acid substitutions in the beta1 strand.

PMID- 22414696
TI  - Dopamine modulation affects the performance of parkinsonian patients in a
      precision motor task measured by an antropomorphic device.
AB  - Several parameters related to the timing, grip force and load force involved in a
      precision grasping task were studied in patients with Parkinson's disease (PD) at
      different moments of medication and healthy controls, using a sensorized
      anthropomorphic device which was totally adapted to the human hand. The aim of
      this work was to carry out an accurate study of the reach-load-grip-hold-place
      release subtasks to identify any physical motor impairment, its relation to
      medication and Parkinsonian strategies. Twenty seven patients in ON and OFF-like
      medication moments, and twenty seven age-matched controls took part in the
      experiment, which consisted of using the index finger and the thumb to perform a
      precision motor task involving different experimental objects. Visual cues were
      used as distracting elements. Results showed several motor parameters impaired in
      OFF-like medication moment but attenuated in ON state, suggesting a medication
      effect on the performance of the task.

PMID- 22414697
TI  - Eosinophilic meningitis without peripheral eosinophilia.

PMID- 22414698
TI  - Topical and systemic cannabidiol improves trinitrobenzene sulfonic acid colitis
      in mice.
AB  - BACKGROUND/AIMS: Compounds of Cannabis sativa are known to exert anti
      inflammatory properties, some of them without inducing psychotropic side effects.
      Cannabidiol (CBD) is such a side effect-free phytocannabinoid that improves
      chemically induced colitis in rodents when given intraperitoneally. Here, we
      tested the possibility whether rectal and oral application of CBD would also
      ameliorate colonic inflammation, as these routes of application may represent a
      more appropriate way for delivering drugs in human colitis. METHODS: Colitis was
      induced in CD1 mice by trinitrobenzene sulfonic acid. Individual groups were
      either treated with CBD intraperitoneally (10 mg/kg), orally (20 mg/kg) or
      intrarectally (20 mg/kg). Colitis was evaluated by macroscopic scoring,
      histopathology and the myeloperoxidase (MPO) assay. RESULTS: Intraperitoneal
      treatment of mice with CBD led to improvement of colonic inflammation.
      Intrarectal treatment with CBD also led to a significant improvement of disease
      parameters and to a decrease in MPO activity while oral treatment, using the same
      dose as per rectum, had no ameliorating effect on colitis. CONCLUSION: The data
      of this study indicate that in addition to intraperitoneal application,
      intrarectal delivery of cannabinoids may represent a useful therapeutic
      administration route for the treatment of colonic inflammation.

PMID- 22414700
TI  - The triad of success in personalised medicine: pharmacogenomics, biotechnology
      and regulatory issues from a Central European perspective.
AB  - The population of the world has recently passed the 7 billion milestone and as
      the cost of human genome sequencing is rapidly declining, sequence data of
      billions of people should be accessible much sooner than anyone would have
      predicted 10 years ago. This will form the basis of personalised medicine.
      However it is still not clear, even in principle, whether these data, combined
      with data of the expression of one's genome in various cells and tissues relevant
      to different diseases, could be used effectively in clinical medicine and
      healthcare, or in predicting responses to different therapies. Therefore this is
      an important issue which needs to be addressed before more resources are wasted
      on less than informative studies and surveys simply because technologies exist.
      As a typical example, we have selected and summarise here key studies from the
      biomedical literature that focus on gene expression profiling of the response to
      biologic therapies in peripheral blood and biopsy samples in autoimmune diseases
      such as rheumatoid arthritis, spondylarthropathy, inflammatory bowel diseases and
      psoriasis. We also present the state of the biotechnology market from a European
      perspective, discuss how spin-offs leverage the power of genomic technologies and
      describe how they might contribute to personalised medicine. As ethical, legal
      and social issues are essential in the area of genomics, we analysed these
      aspects and present here the European situation with a special focus on Hungary.
      We propose that the synergy of these three issues: pharmacogenomics,
      biotechnology and regulatory issues should be considered a triad necessary to
      succeed in personalised medicine.

PMID- 22414699
TI  - Coordinated, multi-joint, fatigue-resistant feline stance produced with
      intrafascicular hind limb nerve stimulation.
AB  - The production of graceful skeletal movements requires coordinated activation of
      multiple muscles that produce torques around multiple joints. The work described
      herein is focused on one such movement, stance, that requires coordinated
      activation of extensor muscles acting around the hip, knee and ankle joints. The
      forces evoked in these muscles by external stimulation all have a complex
      dependence on muscle length and shortening velocities, and some of these muscles
      are biarticular. In order to recreate sit-to-stand maneuvers in the anesthetized
      feline, we excited the hind limb musculature using intrafascicular multielectrode
      stimulation (IFMS) of the muscular branch of the sciatic nerve, the femoral nerve
      and the main branch of the sciatic nerve. Stimulation was achieved with either
      acutely or chronically implanted Utah Slanted Electrode Arrays (USEAs) via
      subsets of electrodes (1) that activated motor units in the extensor muscles of
      the hip, knee and ankle joints, (2) that were able to evoke large extension
      forces and (3) that manifested minimal coactivation of the targeted motor units.
      Three hind limb force-generation strategies were investigated, including
      sequential activation of independent motor units to increase force, and
      interleaved or simultaneous IFMS of three sets of six or more USEA electrodes
      that excited the hip, knee and ankle extensors. All force-generation strategies
      evoked stance, but the interleaved IFMS strategy also reduced muscle fatigue
      produced by repeated sit-to-stand maneuvers compared with fatigue produced by
      simultaneous activation of different motor neuron pools. These results
      demonstrate the use of interleaved IFMS as a means to recreate coordinated,
      fatigue-resistant multi-joint muscle forces in the unilateral hind limb. This
      muscle activation paradigm could provide a promising neuroprosthetic approach for
      the restoration of sit-to-stand transitions in individuals who are paralyzed by
      spinal cord injury, stroke or disease.

PMID- 22414701
TI  - Schistosoma mansoni histones: from transcription to chromatin regulation; an in
      silico analysis.
AB  - Schistosoma mansoni is a human endoparasite with a complex life cycle that also
      infects an invertebrate mollusk intermediate host and exhibits many diverse
      phenotypes. Its complexity is reflected in a large genome and different
      transcriptome profiles specific to each life cycle stage. Epigenetic regulation
      of gene expression such as the post-translational modification of histones has a
      significant impact on phenotypes, and this information storage function resides
      primarily at histone tails, which results in a varied histone code. Evidence of
      transcription of the different histone families at all life stages of the
      parasite was detected by a survey of transcriptome databases; manual curation of
      each gene prediction at the genome sequence level showed errors in the coding
      sequences of three of them. The biogenesis of histones is coupled to DNA
      replication, and a detailed in silico analysis of the specialized machinery of
      histone mRNA processing in the S. mansoni genome reveals that it is as conserved
      as in other eukaryotes, consisting in transcription factors and stem-loop binding
      proteins which recognize the stem loop structure at the histone mRNA 3'UTR.
      Histone modifying enzymes (HMEs) such as histone acetyltransferases,
      methyltransferases and deacetylases (HDACs) have been described in S. mansoni,
      and their potential as new therapeutic targets was evidenced with the apoptotic
      phenotype that resulted from HDAC inhibition. However, the overall regulation of
      transcription coupled with gene expression profiles correlated to histone
      modifications has not yet been characterized. Besides the interaction of HMEs
      with histones, many factors involved in cellular processes are known to bind to
      histones, and were identified here by an in silico analysis of the S. mansoni
      genome. Knowledge of the histone families opens up perspectives for further
      studies that will lead to a better identification of their post-translational
      modifications, their gene regulation and to the possible characterization of HMEs
      as targets for the development of new drugs.

PMID- 22414702
TI  - Design and evaluation of poly(DL-lactic-co-glycolic acid) nanocomposite particles
      containing salmon calcitonin for inhalation.
AB  - Salmon calcitonin, for the treatment of calcium homeostasis and bone remodeling,
      was used as a model peptide drug and adsorbed on the surface of biodegradable
      polymeric poly(dl-lactic-co-glycolic acid) (PLGA) nanospheres. Subsequently, the
      nanospheres were treated using lyophilizer and loaded onto inhalable carrier
      using Mechanofusion to obtain nanocomposite particles suitable for inhalation.
      The physicochemical properties and in vitro inhalation properties of the
      nanocomposite particles were investigated. The pulmonary distribution and
      pharmacological effect were also evaluated in male Wistar rats. The results
      showed that the drug loading efficiency of salmon calcitonin on PLGA nanospheres
      were exceeding 96% (w/w). Inhalation efficiency of the lyophilized PLGA
      nanospheres was largely improved after they were loaded on the surface of
      inhalable carrier. Over 50% (w/w) of the lyophilized PLGA nanospheres could be
      deposited in the alveoli section after intratracheal administration to male
      Wistar rats, while a rapid elimination rate of the lyophilized nanospheres from
      the lung was found in pulmonary distribution study. The in vivo pharmacological
      study showed that the nanocomposite particles exhibited superior hypocalcemic
      action over salmon calcitonion solution and the lyophilized nanospheres. It
      suggested that the Mechanofusion(TM) technique can impart improved inhalation
      properties to the lyophilized nanospheres for pulmonary delivery of therapeutic
      peptide drugs.

PMID- 22414703
TI  - Nephrostomy tube-free versus nephrostomy tube for renal drainage after
      percutaneous nephrolithotomy: a systematic review and meta-analysis.
AB  - BACKGROUND: Historically, percutaneous nephrostomy drainage following
      percutaneous nephrolithotomy (PNL) has been considered the standard of care. More
      recently, however, an increasing number of centers are performing tubeless (with
      insertion of JJ ureteric stent) or totally tubeless (with no internal or external
      drainage) PNL with impressive outcome data. OBJECTIVE: This systematic review is
      to compare the clinical therapeutic efficacy and safety of nephrostomy tube-free
      (NT-free) and standard PNL. MATERIALS AND METHODS: We searched PubMed (1966 to
      April 2011), Embase (1966 to April 2011), and the Cochrane Library without
      language restriction. All randomized controlled trials that compared NT-free PNL
      (using a double-J stent) with standard PNL were enrolled in this review. The
      Cochrane Collaboration's RevMan5.0.2 software was used for statistical analysis.
      RESULTS: Nine studies involving 547 patients were included. Patients were divided
      into 4 groups: NT-free group, small tube group (8-9 Fr), middle tube group (16-18
      Fr), and large tube group (20-24 Fr). Meta-analysis showed that: (1) with regard
      to hospital stay (h) and visual analog scale scores for postoperative pain on day
      1, there was no significant difference between the NT-free group and the small
      tube group, but there were differences between the NT-free group versus the
      middle and large tube groups; (2) for puncture site urinary leakage, no
      significant difference was found between the NT-free group and the small and
      middle tube groups; (3) no significant difference was found with regard to
      transfusion, fever or infection, operative time between the NT-free group and the
      3 tube groups. CONCLUSIONS: The clinical efficacy and safety of NT-free and small
      tube are similar in all measurements. Compared with the middle and large tubes,
      NT-free PNL could reduce hospital stay and postoperative analgesia requirement
      without increasing other complications.

PMID- 22414704
TI  - Effect of dietary fibre of barley variety 'Rihane' on azoxymethane-induced
      aberrant crypt foci development and on colonic microbiota diversity in rats.
AB  - Many epidemiological and experimental studies have suggested an important role
      for dietary fibre (DF) of cereals in the prevention of colon cancer. The
      objective of the present study was to explain the effects of the DF of barley
      Rihane (BR) on azoxymethane (AOM)-induced aberrant crypt foci (ACF) and colonic
      bacterial diversity in rats. Following an acclimatisation period, rats were
      divided into four groups and fed a control (C) diet or experimental diet
      containing 30 % of BR. DF content in the experimental diet was twice that of the
      C diet (total DF was 8.69 % in the C diet and 15.24 % in the BR diet). At 7 and 8
      weeks of age, rats received two successive subcutaneous injections of AOM at 20
      mg/kg body weight. At 12 weeks after the first injection, ten animals from each
      group were killed. The BR diet decreased colonic pH (P < 0.05) compared with the
      C diet. The total number of ACF observed decreased considerably in the BR/AOM
      group compared with the C/AOM group (P < 0.05). Comparison of similarity
      coefficients showed variability of colonic microbiota species between the
      different groups. In addition, we showed inter-individual variability within the
      same group. This similarity was affected by BR and AOM. The present results show
      that bifidobacteria numbers were lower in rats fed the BR diet compared with
      those fed the C diet. However, the number of enterobacteria in colonic content
      was increased (P < 0.05) in the BR group compared with the C group. The results
      from the present study show that the DF of BR reduced the incidence of AOM
      induced ACF and increased microbiota biodiversity.

PMID- 22414705
TI  - Noradrenergic moderation of working memory impairments in adults with autism
      spectrum disorder.
AB  - In addition to having difficulties with social communications, individuals with
      an autism spectrum disorder (ASD) often also experience impairment in higher
      order, executive skills. The present study examined the effects of
      pharmacological modulation of the norepinephrine system on the severity of such
      impairments. A sample of 14 high-functioning adults with ASD and a
      demographically-matched comparison group of 13 typically developing individuals
      participated. An AX continuous performance test (AX-CPT) was used to evaluate
      working memory and inhibitory control. AX-CPT performance was assessed following
      administration of a single dose of propranolol (a beta adrenergic antagonist) and
      following placebo (sugar pill) administration. Individuals with ASD performed
      more poorly than non-ASD individuals in the working memory condition (BX trials).
      Importantly, administration of propranolol attenuated this impairment, with the
      ASD group performing significantly better in the propranolol condition than the
      placebo condition. Working memory performance of the non-ASD group was unaffected
      by propranolol/placebo administration. No group or medication effects were
      observed for the inhibition condition (AY trials). The present findings suggest
      that norepinephrine may play a role in some, but not necessarily all, cognitive
      impairments associated with ASD. Additional research is needed to fully
      understand whether this role is primarily causal or compensatory in nature.

PMID- 22414706
TI  - Anesthesia implications of waterpipe use.
AB  - The waterpipe is an ancient Middle Eastern tobacco delivery system, which is also
      known as hookah, shisha, or narghile, and it is gaining widespread use.
      Waterpipes are often perceived as less dangerous than cigarettes. The amount of
      smoke inhaled in a waterpipe session may equal that produced by more than 100
      cigarettes with high nicotine, carbon monoxide, and carcinogen intake. A case of
      significantly elevated intraoperative carboxyhemoglobin level and decreased
      oxyhemoglobin saturation in a patient with recent waterpipe use is presented.

PMID- 22414707
TI  - Recognition of local anesthetic maldistribution in axillary brachial plexus block
      guided by ultrasound and nerve stimulation.
AB  - Nerve stimulation may occur despite the presence of a fascial barrier between the
      needle tip and the nerve, which may prevent appropriate flow or distribution of
      local anesthetic solution. During an axillary nerve block, ultrasound (US)
      guidance was used to identify the median nerve. Insertion of a needle with US and
      nerve stimulator guidance resulted in the appearance of the needle tip in contact
      with the nerve. However, as local anesthetic injection was begun, it was clear
      that the injectate was accumulating superficial to the investing fascia of the
      neurovascular bundle. No injectate was seen below the fascia. With US guidance,
      the needle was repositioned at a greater depth. Repeat injection of local
      anesthetic clearly flowed around the nerve.

PMID- 22414708
TI  - Ultrasound-guided common peroneal nerve block at the level of the fibular head.
AB  - A common peroneal nerve block at the fibular head is uncommon in clinical
      practice. The case of a 41 year old, morbidly obese woman requiring right total
      ankle replacement is presented. Ultrasound-guided common peroneal nerve block was
      performed at the fibular head after an unsuccessful popliteal approach.

PMID- 22414709
TI  - The dos and do knots of central venous catheterization.
AB  - Central venous catheterization plays an important role in patients with end-stage
      renal disease undergoing hemodialysis. Placement of a right subclavian
      hemodialysis catheter was complicated by looping and entrapment of the guidewire.
      Computed tomographic and three-dimensional scans were essential in locating and
      determining that the guidewire was outside the vessel.

PMID- 22414710
TI  - Use of the DCI video laryngoscope system in a pediatric patient with amniotic
      band syndrome and craniofacial abnormalities affecting the airway.
AB  - A 14 month old, 19 kg female infant with aminotic band syndrome and severe
      craniofacial malformations presented for placement of an open gastrostomy tube.
      Spontaneous ventilation was maintained while an "awake look" was performed with
      the video laryngoscope using intravenous propofol (30 mg total) for sedation. A
      Grade I Cormack-Lehane score was obtained on the monitor. Succinylcholine was
      then administered intravenously and orotracheal intubation was performed on the
      first attempt with a size 4.5 endotracheal tube.

PMID- 22414711
TI  - Blood utilization: fostering an effective hospital transfusion culture.
AB  - An effective hospital transfusion culture should encourage clinicians to consider
      the possibility of transfusion in their patients well before the need actually
      arises, and to plan ahead in an attempt to use blood products most efficiently.
      Strategies for improved blood utilization include timely and adequate
      preoperative assessment of risk, optimization of baseline hemoglobin,
      anticipation of potential transfusion problems, intraoperative techniques to
      minimize blood loss, blood conservation technologies, transfusion guidelines and
      targeted therapy, point of care testing, and massive transfusion protocols.
      Attention to these elements promotes a safe and cost-effective transfusion
      culture.

PMID- 22414712
TI  - Ultrasound versus nerve stimulator: what's missing and is it really important?

PMID- 22414714
TI  - Proper depth placement of oral endotracheal tubes in adults: 21/23 cm or 20/22
      cm?

PMID- 22414716
TI  - The "rotated mask hold" and "chin lift grip" may improve the one-hand face mask
      ventilation airway maneuver.

PMID- 22414717
TI  - Makeshift jet ventilator setup.

PMID- 22414718
TI  - Urgent laparotomy helped resuscitate a neonate with increased intra-abdominal
      pressure who had cardiac arrest with anesthetic induction.

PMID- 22414719
TI  - Tramadol for postdural puncture headache treatment in a pediatric patient
      following failed blood patch.

PMID- 22414720
TI  - Unexpected failed intubation with the introducer bougie-assisted Airtraq
      technique using the Parker Flex-Tip Tube.

PMID- 22414721
TI  - Anaphylactic shock during liver hydatid cyst surgery.

PMID- 22414722
TI  - The two different effects of the potential neuroprotective compound minocycline
      on AMPA-type glutamate receptors.
AB  - BACKGROUND: Minocycline has demonstrated neuroprotective effects in experimental
      neurodegenerative diseases. The aim of this study was to investigate if there is
      any direct interaction between minocycline and the AMPA-type receptor channels,
      and to elucidate the underlying molecular pharmacological mechanisms. METHODS:
      The patch-clamp technique was used combined with an ultrafast solution exchange
      system to investigate the interaction of minocycline with recombinant AMPA-type
      glutamate receptor channels (homomeric GluR2flipGQ or nondesensitizing
      GluR2L504Y). RESULTS: Dose-dependent decreases in the relative peak current
      amplitude (rAmp) and the relative steady-state current (rC(des)) were found in
      coapplication experiments with GluR2L504Y receptors, but not in preincubation
      experiments. Furthermore, coapplication of 1 or 3 mmol/l minocycline showed a
      decrease in the fast time constant of current decay, and reopening currents were
      observed. But in the test with GluR2flipGQ receptors, rAmp, relative area under
      the curve and rC(des) increased with increasing concentrations of minocycline,
      and the steady-state time constant also increased when 3 MUmol/l glutamate were
      used as agonist. CONCLUSION: Minocycline modulates AMPA-type receptor channels in
      a combination of a weaker open-channel block effect and a stronger potentiation
      effect, and the latter effect arises mainly from attenuating the extent of
      receptor desensitization.

PMID- 22414723
TI  - Indication for random skin biopsy for the diagnosis of intravascular large B cell
      lymphoma.
AB  - BACKGROUND: The use of random skin biopsy (RSB) to diagnose intravascular large B
      cell lymphoma (IVLBCL) has increased. OBJECTIVE: To explore the indication for
      RSB to diagnose IVLBCL. METHODS: We retrospectively evaluated the medical records
      of 18 Japanese adults who underwent RSB between January 2008 and December 2009.
      RESULTS: A final diagnosis of IVLBCL was returned in 2 patients based on RSB
      findings and in 1 based on brain biopsy findings. All 3 patients manifested
      neurological symptoms, hematocytopenia, elevated levels of LDH and soluble
      interleukin-2 receptor (sIL-2R), and the absence of lymphadenopathy. Malignant
      lymphoma other than IVLBCL was diagnosed in 6 patients, and in 5 of 6 patients
      who underwent nodal or parenchymal biopsy diagnostic findings were made.
      CONCLUSION: Although RSB is useful for the early diagnosis of IVLBCL, careful
      selection of patients is necessary. In patients with neurological symptoms,
      hematocytopenia, elevated LDH and sIL-2R and no nodal involvement, RSB may be
      useful.

PMID- 22414724
TI  - Knowledge of risk factors and stroke symptoms among nonstroke patients.
AB  - BACKGROUND AND PURPOSE: This study aimed to evaluate knowledge of stroke warning
      signs, risk factors, treatment and prevention among patients not suffering from
      stroke. METHODS: Patients admitted to one of five Neurology Departments in Poland
      for diseases other than stroke were asked to answer a questionnaire regarding
      awareness of cerebrovascular risk factors and stroke. The study was performed
      between November 1 and December 31,2008. RESULTS: 481 patients were included in
      the study (59.7% women). Proper definition of stroke and transient ischemic
      attack was given by 90.3 and 60.5% of respondents, respectively. Hypertension was
      reported as a risk factor by 91.1% of participants. Approximately 70% knew that
      hypercholesterolemia and smoking are risk factors of stroke, but only one third
      identified diabetes mellitus as a risk factor. Cardiac arrhythmia was recognized
      as a risk factor by 8.4%. Twenty-five percent of participants did not know any
      symptom of stroke. Identification of stroke signs was worse by participants from
      rural areas. Ten percent identified disturbances of consciousness, numbness, and
      dizziness as stroke symptoms. CONCLUSIONS: The knowledge of fundamental risk
      factors was sufficiently good, but recognition of cardiac arrhythmia and diabetes
      mellitus was unsatisfactory. The knowledge of stroke symptoms was unsatisfactory,
      particularly in rural areas. Additional education programs are necessary.

PMID- 22414726
TI  - Activation of DNA damage response pathways as a consequence of anthracycline-DNA
      adduct formation.
AB  - The cytotoxicity of doxorubicin, a clinically used anti-neoplastic drug, can be
      enhanced by formaldehyde (either endogenous or exogenous) to promote the
      formation of doxorubicin-DNA adducts. Formaldehyde supplies the carbon required
      for the covalent linkage of doxorubicin to one strand of DNA, with hydrogen bonds
      stabilising the doxorubicin mono-adduct to the other strand of DNA, to act much
      like an interstrand crosslink. Interstrand crosslinks present a major challenge
      for cellular repair processes, requiring the activation of numerous DNA damage
      response proteins for resolution of the resulting DNA intermediates and damage.
      This work investigates DNA damage response proteins activated by doxorubicin-DNA
      adducts. Although p53 was phosphorylated at Serine 15 in response to adducts,
      long term growth inhibition of mammalian cells was not affected by p53 status.
      Using siRNA technology and kinase inhibitors we observed enhanced cellular
      sensitivity to doxorubicin-DNA adducts when the activity of the signalling
      protein kinases ATM and ATR were lost. Cells synchronised using a double
      thymidine block were sensitised to adduct-initiated cell death upon ATR
      knockdown, but relatively unaffected by ATM knockdown. Loss of ATR was associated
      with abrogation of a drug-induced G(2)/M block and induction of mitotic
      catastrophe, while loss of ATM was associated with drug-induced apoptosis in non
      synchronised cells. These proteins may therefore be potential drug targets to
      achieve synergistic cytotoxic responses to doxorubicin-DNA adduct forming
      therapies. The analysis of these protein kinases with respect to cell cycle
      progression indicates that ATR is required for G(2)/M checkpoint responses while
      ATM appears to function in G(1) mediated responses to anthracycline adducts.

PMID- 22414725
TI  - GW583340 and GW2974, human EGFR and HER-2 inhibitors, reverse ABCG2- and ABCB1
      mediated drug resistance.
AB  - The overexpression of ATP binding cassette (ABC) transporters often leads to the
      development of multidrug resistance (MDR) and results in a suboptimal response to
      chemotherapy. Previously, we reported that lapatinib (GW572016), a human
      epidermal growth factor receptor (EGFR) and HER-2 tyrosine kinase inhibitor
      (TKI), significantly reverses MDR in cancer cells by blocking the efflux function
      of ABC subfamily B member 1 (ABCB1) and ABC subfamily G member 2 (ABCG2). In the
      present study, we conducted in vitro experiments to evaluate if GW583340 and
      GW2974, structural analogues of lapatinib, could reverse ABCB1- and ABCG2
      mediated MDR. Our results showed that GW583340 and GW2974 significantly
      sensitized ABCB1 and ABCG2 overexpressing MDR cells to their anticancer
      substrates. GW583340 and GW2974 significantly increased the intracellular
      accumulation of [(3)H]-paclitaxel in ABCB1 overexpressing cells and [(3)H]
      mitoxantrone in ABCG2 overexpressing cells respectively. In addition, GW583340
      and GW2974 significantly inhibited ABCG2-mediated transport of methotrexate in
      ABCG2 overexpressing membrane vesicles. There was no significant change in the
      expression levels of ABCB1 and ABCG2 in the cell lines exposed to 5MUM of either
      GW583340 or GW2974 for 3 days. In addition, a docking model predicted the binding
      conformation of GW583340 and GW2974 to be within the transmembrane region of
      homology modeled human ABCB1 and ABCG2. We conclude that GW583340 and GW2974, at
      clinically achievable plasma concentrations, reverse ABCB1- and ABCG2-mediated
      MDR by blocking the drug efflux function of these transporters. These findings
      may be useful in developing combination therapy for cancer treatment with EGFR
      TKIs.

PMID- 22414727
TI  - Investigation of imatinib and other approved drugs as starting points for
      antidiabetic drug discovery with FXR modulating activity.
AB  - A self-organizing map (SOM) is a virtual screening method used for correlation of
      molecular structure and potential biological activity on a certain target and
      offers a way to represent multi-dimensional data of large databases in a two
      dimensional space. Large databases, for example the DrugBank database, provide
      information about biological activity and chemical structure of small molecules
      and are widely used in drug development for identification of new lead
      structures. The farnesoid X receptor (FXR) is a ligand activated transcription
      factor involved in key regulation mechanisms within glucose and lipid
      homeostasis. Although FXR became an established target in drug development for
      diseases associated with lipid, glucose or hepatic disorders during the last
      decade, none of the developed compounds have reached later phases of clinical
      development so far. We used a SOM trained with known FXR ligands to screen the
      DrugBank database for potential ligands for FXR. In this article, we report the
      successful identification of six approved drugs out of the Drugbank as FXR
      modulators (ketoconazole, pentamidine, dobutamine, imatinib, papaverine and
      montelukast) by using a SOM for screening of the DrugBank database. We show FXR
      modulation by selected compounds in a full length FXR transactivation assay and
      modulation of a FXR target gene by imatinib.

PMID- 22414728
TI  - A latent discriminative model-based approach for classification of imaginary
      motor tasks from EEG data.
AB  - We consider the problem of classification of imaginary motor tasks from
      electroencephalography (EEG) data for brain-computer interfaces (BCIs) and
      propose a new approach based on hidden conditional random fields (HCRFs). HCRFs
      are discriminative graphical models that are attractive for this problem because
      they (1) exploit the temporal structure of EEG; (2) include latent variables that
      can be used to model different brain states in the signal; and (3) involve
      learned statistical models matched to the classification task, avoiding some of
      the limitations of generative models. Our approach involves spatial filtering of
      the EEG signals and estimation of power spectra based on autoregressive modeling
      of temporal segments of the EEG signals. Given this time-frequency
      representation, we select certain frequency bands that are known to be associated
      with execution of motor tasks. These selected features constitute the data that
      are fed to the HCRF, parameters of which are learned from training data.
      Inference algorithms on the HCRFs are used for the classification of motor tasks.
      We experimentally compare this approach to the best performing methods in BCI
      competition IV as well as a number of more recent methods and observe that our
      proposed method yields better classification accuracy.

PMID- 22414729
TI  - Commentary: the use of health and behavior codes in pediatric psychology: where
      are we now?
AB  - This article focuses on the current status of the use of Health and Behavior
      (H&B) codes by pediatric psychologists. We address the rationale for the use of
      these codes in a pediatric psychology setting, practice updates since the codes
      were initiated, and our experience with utilizing these codes in one pediatric
      hospital. We conclude with a summary of our assertions and future directions for
      policy and practice.

PMID- 22414730
TI  - The abnormal processing of TDP-43 is not an upstream event of reduced ADAR2
      activity in ALS motor neurons.
AB  - TDP-43 pathology in motor neurons is a hallmark of ALS. In addition, the reduced
      expression of an RNA editing enzyme, adenosine deaminase acting on RNA 2 (ADAR2),
      increases the expression of GluA2 with an unedited Q/R site in the motor neurons
      of patients with sporadic ALS. As the occurrence of these two disease-specific
      abnormalities in the same motor neurons suggests a molecular link between them,
      we examined the effects of altered TDP-43 processing on ADAR2 activity in
      TetHeLaG2m and Neuro2a cells. We found that ADAR2 activity did not consistently
      change due to the overexpression or knockdown of TDP-43 or the expression of
      abnormal TDP-43, including caspase-3-cleaved fragments, truncated TDP-43 lacking
      either nuclear localization or export signals and ALS-linked TDP-43 mutants.
      These results suggest that the abnormal processing of TDP-43 is not an upstream
      event of inefficient GluA2 Q/R site editing in the motor neurons of sporadic ALS
      patients.

PMID- 22414731
TI  - Paclitaxel-loaded ethosomes(r): potential treatment of squamous cell carcinoma, a
      malignant transformation of actinic keratoses.
AB  - Topical application of anticancer drugs for the treatment of malignancies
      represents a new challenge in dermatology, potentially being an alternative
      therapeutic approach for the efficacious treatment of non-melanoma skin cancer,
      that is, actinic keratoses, and malignant lesions of the skin caused by
      ultraviolet radiation. Anti-proliferative and antimitotic drugs, including many
      of the taxanes, are currently under investigation for the treatment of cutaneous
      malignant transformation of actinic keratoses, particularly the squamous cell
      carcinoma. Paclitaxel-loaded ethosomes(r) are proposed as topical drug delivery
      systems for the treatment of this pathology due to their suitable physicochemical
      characteristics and enhanced skin penetration ability for deep dermal delivery.
      Our in vitro data show that the skin application of paclitaxel-loaded
      ethosomes(r) improved the permeation of paclitaxel in a stratum corneum-epidermis
      membrane model and increased its anti-proliferative activity in a squamous cell
      carcinoma model as compared to the free drug. The results obtained encouraged the
      use of the paclitaxel-loaded ethosomes(r) as the formulation for the potential
      treatment of squamous cell carcinoma, a malignant transformation of actinic
      keratoses.

PMID- 22414732
TI  - Nocturnal changes in knee cartilage thickness in young healthy adults.
AB  - Magnetic resonance imaging (MRI) allows one to analyze cartilage physiology in
      vivo. Cartilage deforms during loading, but little is known about its recovery
      after deformation. Here we study 'nocturnal' changes in knee cartilage thickness
      and whether postexercise deformation differs between morning and evening. Axial
      magnetic resonance (MR) images were acquired in the right knees of 17 healthy
      volunteers (age 23.5 +/- 3.0 years) after a normal day, and then after 30 deep
      knee bends. Coronal images were additionally acquired in 8 of these volunteers
      after a normal day and then after 2 min of static loading of the leg with 150%
      body weight. The volunteers then remained unloaded overnight and the same
      protocol was repeated in the morning. A significant increase (p < 0.01) in
      cartilage thickness was observed between evening (preexercise) and morning
      (preexercise): +2.4% in the patella, +8.4% in the medial tibia and +6.2% in the
      lateral tibia. Deformation in the morning (-6.8/ -4.6/-5.1%) was generally
      greater than that in the evening (-5.4/-3.2/-3.7%), but this difference did not
      reach statistical significance. No significant difference in the nocturnal
      thickness increase (or postexercise deformation) was observed between men and
      women. We conclude that knee cartilage (thickness) recovers overnight by
      approximately 2-8%, independent of sex. Given the lack of 'predeformation' after
      nocturnal periods of unloading, morning postexercise deformation of the cartilage
      may have a greater magnitude than evening postexercise deformation.

PMID- 22414733
TI  - Differential effects of low-dose resveratrol on adiposity and hepatic steatosis
      in diet-induced obese mice.
AB  - Consumption of a high-fat diet (HFD) enriched in saturated fat induces excessive
      weight gain due to adiposity, which can lead to metabolic complications, as well
      as increased risk of fatty liver disease and CVD. The present study investigated
      the underlying mechanism and dose-response effects of resveratrol (RV) on
      obesity, hepatic steatosis and dyslipidaemia in mice fed a HFD. Male C57BL/6J
      mice were fed a normal diet or a HFD (20 % fat, w/w) combined with 0.005 or 0.02
      % (w/w) RV for 10 weeks. As expected, mice fed a HFD developed obesity, as shown
      by increased body weight gain, visceral fat, hepatic fat and plasma cholesterol.
      RV significantly reduced visceral fat and plasma NEFA. In the liver of HFD-fed
      mice, RV significantly reduced TAG and cholesterol, as well as lipid droplet
      number and size. A low dose of RV (0.005 %) appeared to be more effective than a
      higher dose of RV (0.02 %) for suppressing adiposity and hepatic steatosis
      development with a significant decrease in body weight gain, plasma TAG and total
      cholesterol levels. These changes were seemingly attributable to a suppression of
      the fatty acid (FA) synthase, glucose-6-phosphate dehydrogenase, and
      phosphatidate phosphohydrolase and/or an activation of FA oxidation in the liver
      and epididymal adipose tissue. In conclusion, daily consumption of a low dose of
      RV is effective for protecting against diet-induced obesity, hepatic steatosis
      and dyslipidaemia in HFD-fed mice.

PMID- 22414734
TI  - Maternal-child overweight/obesity and undernutrition in Kenya: a geographic
      analysis.
AB  - OBJECTIVE: The purpose of the study was to examine geographic relationships of
      nutritional status (BMI), including underweight, overweight and obesity, among
      Kenyan mothers and children. DESIGN: Spatial relationships were examined
      concerning BMI of the mothers and BMI-for-age percentiles of their children.
      These included spatial statistical measures of the clustering of segments of the
      population, in addition to inspection of co-location of significant clusters.
      SETTING: Rural and urban areas of Kenya, including the cities of Nairobi and
      Mombasa, and the Kisumu region. SUBJECTS: Mother-child pairs from Demographic and
      Health Survey data including 1541 observations in 2003 and 1592 observations in
      2009. These mother-child pairs were organized into 399 locational clusters.
      RESULTS: There is extremely strong evidence that high BMI values exhibit strong
      spatial clustering. There were co-locations of overweight mothers and overweight
      children only in the Nairobi region, while both underweight mothers and children
      tended to cluster in rural areas. In Mombasa clusters of overweight mothers were
      associated with normal-weight children, while in the Kisumu region clusters of
      overweight children were associated with normal-weight mothers. CONCLUSIONS:
      These findings show there is geographic variability as well as some defined
      patterns concerning the distribution of malnutrition among mothers and children
      in Kenya, and suggest the need for further geographic analyses concerning the
      potential factors which influence nutritional status in this population. In
      addition, the methods used in this research may be easily applied to other
      Demographic and Health Survey data in order to begin to understand the geographic
      determinants of health in low-income countries.

PMID- 22414735
TI  - Mentoring in gynecologic oncology fellowship training and beyond.

PMID- 22414737
TI  - Temperamental surgency and emotion regulation as predictors of childhood social
      competence.
AB  - The primary aims of the current study were to longitudinally examine the direct
      relationship between children's temperamental surgency and social behaviors as
      well as the moderating role of children's emotion regulation. A total of 90 4.5
      year-old children participated in a laboratory visit where children's
      temperamental surgency was rated by experimenters and children's emotion
      regulation abilities were assessed. The summer before entry into first grade,
      children's social behaviors with unfamiliar peers were observed in the laboratory
      and mothers completed a questionnaire about children's social behaviors.
      Supporting our hypotheses, results revealed that children high in temperamental
      surgency developed more negative peer behaviors, whereas children low in
      temperamental surgency were more likely to develop behavioral wariness with
      peers. Emotion regulatory behaviors were found to moderate the relation between
      temperamental surgency and aggression, where high-surgent children who showed
      high levels of social support seeking were less likely to be rated by their
      mothers as high in aggression. Furthermore, results revealed that low-surgent
      children who showed high levels of distraction/self-soothing were more likely to
      show behavioral wariness around unfamiliar peers, whereas high-surgent children
      who used more distraction/self-soothing behaviors were rated by their mothers as
      lower in social competence.

PMID- 22414738
TI  - Subliminal food images compromise superior working memory performance in women
      with restricting anorexia nervosa.
AB  - Prefrontal cortex (PFC) is dysregulated in women with restricting anorexia
      nervosa (RAN). It is not known whether appetitive non-conscious stimuli bias
      cognitive responses in those with RAN. Thirteen women with RAN and 20 healthy
      controls (HC) completed a dorsolateral PFC (DLPFC) working memory task and an
      anterior cingulate cortex (ACC) conflict task, while masked subliminal food,
      aversive and neutral images were presented. During the DLPFC task, accuracy was
      higher in the RAN compared to the HC group, but superior performance was
      compromised when subliminal food stimuli were presented: errors positively
      correlated with self-reported trait anxiety in the RAN group. These effects were
      not observed in the ACC task. Appetitive activation is intact and anxiogenic in
      women with RAN, and non-consciously interacts with working memory processes
      associated with the DLPFC. This interaction mechanism may underlie cognitive
      inhibition of appetitive processes that are anxiety inducing, in people with AN.

PMID- 22414739
TI  - A simple and rapid quantitative sweat test based on cobalt chloride color change.
AB  - BACKGROUND: Existing sweat tests are either cumbersome, require dedicated
      technical equipment and/or do not give reliable quantitative results. The present
      study was performed to develop and describe a rapid and simple test for a
      practical and quantitative evaluation of sweating. METHODS: Cobalt chloride
      patches were used to collect sweat during exercise and after application of
      aluminum hydrochloride. Color change from blue to red was recorded and
      quantified, and the amount of sweat was calculated from a standard curve.
      RESULTS: Cobalt-chloride-containing patches evaluated with standard office
      equipment provide a rapid, simple and highly sensitive method for the
      quantitative measurement of sweating. CONCLUSIONS: Possible applications that
      need to be evaluated in further studies are the diagnosis and monitoring of
      diseases associated with disordered sweat production and the evaluation of
      antiperspirants.

PMID- 22414740
TI  - The vaccination coverage required to establish herd immunity against influenza
      viruses.
AB  - OBJECTIVE: 1) To determine the influenza vaccination coverage required to
      establish herd immunity, and 2) to assess whether the percentages of vaccination
      coverage proposed and those registered in the United States and Europe are
      sufficient to establish herd immunity. METHODS: The vaccination coverage required
      to establish herd immunity was determined by taking into account the number of
      secondary cases per infected case (R(o)) and the vaccine effectiveness. RESULTS:
      The required percentage that would have been required to establish herd immunity
      against previous influenza viruses ranged from 13% to 100% for the 1918-19, 1957
      58, 1968-69 and 2009-10 pandemic viruses, and from 30% to 40% for the 2008-09
      epidemic virus. The objectives of vaccination coverage proposed in the United
      States - 80% in healthy persons and 90% in high-risk persons - are sufficient to
      establish herd immunity, while those proposed in Europe - only 75% in elderly and
      high-risk persons - are not sufficient. The percentages of vaccination coverage
      registered in the United States and Europe are not sufficient to establish herd
      immunity. CONCLUSION: The influenza vaccination coverage must be increased in the
      United States and Europe in order to establish herd immunity. It is necessary to
      develop new influenza prevention messages based on herd immunity.

PMID- 22414741
TI  - Risk of smoking and body mass index for incidence of diabetes mellitus in a rural
      Japanese population.
AB  - OBJECTIVE: To assess the risk of smoking, body mass index (BMI), and both for
      incidence of diabetes in a rural Japanese population. METHOD: This study was a
      10.1-year cohort study of 2070 men and 3802 women aged 40-69 years without
      diabetes at baseline who underwent a health check-up at one central hospital in
      Nagano Prefecture. Participants were classified according to a combination of
      smoking status and BMI. Participants were followed from 1990 to 2006. The
      incidence of diabetes was determined from fasting and random levels of plasma
      glucose, HbA(1c) levels or being under medical treatment for diabetes. RESULTS:
      Diabetes developed in 595 of the participants during 59,111 person-years of
      follow-up. In men, the multivariable-adjusted hazard ratios for incidence of
      diabetes compared with non-smokers of normal weight were as follows: 3.36 (2.02
      5.60) in current smokers with normal weight and 1.70 (0.87-3.34) and 3.93 (2.22
      6.96) in obese non-smokers and obese current smokers, respectively. In men the
      population-attributable fraction of diabetes onset due to current smoking,
      obesity and both were 22.0%, 2.5% and 11.2%, respectively. CONCLUSION: Regardless
      of BMI, smoking is an important risk factor for diabetes in male populations with
      a high prevalence of smoking.

PMID- 22414742
TI  - Reassessment of sst3 somatostatin receptor expression in human normal and
      neoplastic tissues using the novel rabbit monoclonal antibody UMB-5.
AB  - BACKGROUND: Among the five somatostatin receptors (sst(1)-sst(5)), the sst(3)
      receptor displays a distinct pharmacological profile. Like sst(2), the sst(3)
      receptor efficiently internalizes radiolabeled somatostatin analogs. Unlike
      sst(2), however, internalized sst(3) receptors are rapidly transferred to
      lysosomes for degradation. Apart from this, very little is known about the
      clinical relevance of the sst(3) receptor, which may in part be due to the lack
      of specific monoclonal sst(3) antibodies. METHODS: Here, we have extensively
      characterized the novel rabbit monoclonal anti-human sst(3) antibody UMB-5 using
      transfected cells and receptor-expressing tissues. UMB-5 was then subjected to
      immunohistochemical staining of a series of 190 formalin-fixed, paraffin-embedded
      normal and neoplastic human tissues. RESULTS: Specificity of UMB-5 was
      demonstrated by detection of a broad band migrating at a molecular weight of
      70,000-85,000 in immunoblots from human pituitary. After enzymatic
      deglycosylation, the size of this band decreased to a molecular weight of 45,000.
      Tissue immunostaining was completely abolished by pre-adsorption of UMB-5 with
      its immunizing peptide. In addition, UMB-5 detected distinct cell populations in
      human tissues like pancreatic islands, anterior pituitary, adrenal cortex,
      adrenal medulla, and enteric ganglia, similar to that seen with a rabbit
      polyclonal antibody generated against a different carboxyl-terminal epitope of
      the sst(3) receptor. In a comparative immunohistochemical study, UMB-5 yielded
      predominant plasma membrane staining in the majority of pituitary adenomas,
      pheochromocytomas, and a subset of neuroendocrine tumors. The sst(3) receptor was
      also present in many glioblastomas, pancreatic, breast, cervix, and ovarian
      carcinomas. CONCLUSION: The rabbit monoclonal antibody UMB-5 may prove of great
      value in the identification of sst(3)-expressing tumors during routine
      histopathological examinations. Given its unique trafficking properties, these
      tumors may be potential candidates for sst(3)-directed receptor radiotherapy.

PMID- 22414744
TI  - Stress reactivity and the Hemodynamic Profile-Compensation Deficit (HP-CD) Model
      of blood pressure regulation.
AB  - Considering the central role of the concept of blood pressure reactivity to
      explanations of the influence of life stress in the pathogenesis of
      cardiovascular disease, it is important that the underlying psychophysiological
      determinants of blood pressure change are elucidated. Empirical evidence is
      reviewed concerning the utility of the Hemodynamic Profile-Compensation Deficit
      (HP-CD) Model (Gregg et al., 2002), which draws on physiological theory that
      explains blood pressure regulation as a dynamic compensatory relation between
      cardiac output and total peripheral resistance. Core constructs and quantitative
      features of the Model are explained, accompanied by a focussed review of the
      Model's application in reactivity studies of stress, lifestyle behaviours,
      laboratory-to-field generalisability, and personality differences. Although the
      available studies are relatively few in number, evidence of the Model's utility
      is promising. Application of the Model in further research could help to
      elucidate cardiovascular pathogenesis in ways not achievable through the study of
      blood pressure reactivity alone.

PMID- 22414745
TI  - Cardiac vagal control as a prospective predictor of anxiety in women diagnosed
      with breast cancer.
AB  - Low cardiac vagal control (CVC) has been associated with state and trait anxiety
      and anxiety spectrum disorders. Studies indicate that diagnosis and treatments
      for breast cancer may be associated with anxiety. The current study examined
      whether CVC prospectively predicted a trajectory of change in anxiety following
      breast cancer diagnosis. Forty-three women diagnosed with non-metastatic breast
      cancer completed the Taylor Manifest Anxiety Scale and the Perceived Stress
      Scale, and a 5-min resting electrocardiographic (ECG) segment was recorded. Self
      report measures were completed approximately every 3 months for a year.
      Respiratory sinus arrhythmia (RSA) significantly predicted the trajectory of
      change in anxiety over the follow-up period: participants with higher baseline
      RSA evidenced decreasing anxiety, whereas those with lower baseline RSA had
      increasing anxiety. These results are consistent with the hypothesis that CVC
      facilitates the modulation of anxiety in women coping with significant stressors
      of breast cancer diagnosis and treatment.

PMID- 22414746
TI  - Molecular characterization of amelogenesis imperfecta in Chinese patients.
AB  - BACKGROUND: Mutations in 6 genes have been identified as being part of the
      etiology of amelogenesis imperfecta (AI) with various phenotypes in an isolated
      condition. Among them the FAM83H gene is the major contributor to the etiology of
      AI with unknown function. OBJECTIVE: This study aims to determine the phenotypic
      and molecular characterization of Chinese AI patients and to analyze the
      structure and function of the FAM83H protein. METHODS: We enrolled 6
      hypocalcified AI and 3 hypoplastic AI families from the Chinese population.
      Mutation analysis was performed by amplifying and sequencing all exons including
      intron-exon borders for FAM83H and ENAM genes. Structural modeling and function
      analysis on the FAM83H protein were carried out by bioinformatic processing.
      RESULTS: No obvious anterior open bite was observed in all the investigated
      individuals. Five mutations (c.906T>G, c.924dupT, c.973C>T, c.1354C>T and
      c.2029C>T) in the C-terminal of the FAM83H gene were revealed, respectively, in 5
      out of 6 hypocalcified AI families, and a splicing mutation c.534 + 1G>A in the
      ENAM gene was identified in 1 out of 3 hypoplastic AI families. Structural models
      of the N- and C-terminal regions of FAM83H were generated by homology modeling.
      The predicted structure of the FAM83H N-terminal shows resemblance to that of
      glycosyltransferases with GT-A folds, and the predicted structure of the FAM83H C
      terminal possesses similarity to type I collagen protein. CONCLUSIONS: To our
      knowledge, this is the first report of AI with specific molecular variations in
      families of Chinese descent. Our study provides new insights into the structure
      and function of the FAM83H protein.

PMID- 22414748
TI  - Response to Klyuyev and Vassylyev: on the mechanism of tagetitoxin inhibition of
      transcription.
AB  - In their commentary, Klyuyev and Vassylyev dispute a model of transcription
      inhibition by tagetitoxin (Tgt) proposed by us based on biochemical analysis and
      computational docking. We maintain that, although an alternative explanation can
      be provided for any single observation reported by us, taken together our results
      support a model in which Tgt acts by trapping the trigger loop (TL) in an
      inactive state (Artsimovitch et al.). This model is consistent with all the data
      collected with a physiological target for the inhibitor, the transcription
      elongation complex (EC). The Tgt-binding pose in our model is indeed different
      from that observed in the structure of the Thermus thermophilus RNA polymerase
      (RNAP) holoenzyme in the absence of nucleic acids (Vassylyev et al. Nat Struct
      Mol Biol 2005; 12:1086). The latter can hardly be considered a dogma because RNAP
      undergoes conformational changes in the course of the transcription cycle and
      during catalysis and small molecules containing phosphates likely bind to several
      sites on RNAP, with the crystallographic site/pose not necessarily being the one
      most relevant mechanistically. Furthermore, the model proposed based on the
      Tgt/holoenzyme structure does not explain the inhibitor's effects on transcript
      elongation and RNAP translocation. These arguments necessitate further inquiry
      into the mechanism of inhibition by Tgt by techniques orthogonal to X-ray
      crystallography. In our opinion, elucidation of a molecular mechanism of any RNAP
      inhibitor and the follow-up design of more potent derivatives requires a
      combination of approaches, including genetics, biochemistry, biophysics, X-ray
      crystallography and computational analysis.

PMID- 22414749
TI  - Synthetic in vitro transcription circuits.
AB  - With the help of only two enzymes--an RNA polymerase and a ribonuclease--reduced
      versions of transcriptional regulatory circuits can be implemented in vitro.
      These circuits enable the emulation of naturally occurring biochemical networks,
      the exploration of biological circuit design principles and the biochemical
      implementation of powerful computational models.

PMID- 22414750
TI  - CTCF-dependent chromatin insulator as a built-in attenuator of angiogenesis.
AB  - VEGF is a pivotal pro-angiogenic growth factor and its dosage decisively impacts
      vascularization. We recently identified a CTCF-dependent chromatin insulator that
      critically restrains the transcriptional induction of VEGF and angiogenesis. We
      postulate that CTCF may exert enhancer blocking by mediating chromatin looping
      and/or RNA polymerase pausing at the VEGF locus.

PMID- 22414751
TI  - Transcriptional control of Gad2.
AB  - Gad2 encodes GAD65, which is present preferentially in presynaptic terminals for
      synthesis of GABA for vesicle release. Gad2 is a regulatory target of cell
      activities in various brain functions and in GABA perturbation-related
      neurological diseases. However, our understanding of how Gad2 is
      transcriptionally regulated and how Gad2 transcription responds to changing cell
      environment under these conditions is still limited. This review discusses recent
      advances in the regulatory mechanisms for Gad2 transcription and highlights the
      characteristics of TATA-less Gad2 promoters and regulation of Gad2 transcription
      by CREB and by activity-dependent epigenetic modification of the chromatin
      structure in regulatory elements of the Gad2 gene.

PMID- 22414752
TI  - A novel mechanism of bacterial adaptation mediated by copper-dependent RNA
      polymerase sigma factors.
AB  - One of the mechanisms widely used by bacteria to adapt to their environment is
      mediated by alternative sigma factors. Here we discuss the mechanism of action of
      a novel metal-dependent ECF sigma factor, whose ability to bind DNA depends on
      the redox state of copper.

PMID- 22414753
TI  - Mapping gene-environment interactions at regulatory polymorphisms: insights into
      mechanisms of phenotypic variation.
AB  - Genetic effects on gene regulation make a substantial contribution to phenotypic
      diversity, yet their mechanisms remain elusive. Here, we discuss the potential
      insights to be gained from mapping gene-environment interactions at regulatory
      polymorphisms (i.e., genetic variation that affects gene expression under
      specific environmental conditions). We highlight a novel statistical method to
      identify specific patterns of gene-environment interaction at these regulatory
      polymorphisms. Reviewing its application to a study that mapped gene expression
      in the presence and absence of glucocorticoids, we discuss the mechanistic
      insights that this approach provides.

PMID- 22414754
TI  - The binding site and mechanism of the RNA polymerase inhibitor tagetitoxin: an
      issue open to debate.
AB  - In a recent paper in the Journal of Biological Chemistry, Artsimovitch et al.
      report a major revision of a crystallographic model and proposed mechanism of the
      RNA polymerase inhibitor, tagetitoxin. This reassessment is based on theoretical
      modeling using molecular dynamics simulations. Here, we argue that this
      theoretical model contradicts experimental results and a published crystal
      structure cannot exclude several mechanistically distinct alternative models and
      does not support some major conclusions. We conclude that understanding the
      tagetitoxin mechanism is beyond the reach of currently available computational
      simulations and must await input from high-resolution crystal structures of
      tagetitoxin bound to elongation complex, extensive biochemical studies, or both.

PMID- 22414756
TI  - Low-dose cyclosporine mediates donor hyporesponsiveness in a fully mismatched rat
      kidney transplant model.
AB  - Tolerance induction protocols have been successfully tested in animal models, yet
      their compatibility with immunosuppressive drugs remains to be fully elucidated.
      Our own previous data have indicated that cyclosporine A (CsA) affects the
      balance of effector and regulatory mechanisms with low-dose CsA doses promoting
      hyporesponsiveness. Here, we present a fully mismatched rat kidney model in which
      low-dose CsA treatment induces donor hyporesponsiveness to secondary renal
      allografts. Lewis recipients of DA kidney grafts received low, medium or high
      doses of CsA * 10 days. By 30 days, the primary transplant was removed and a
      second transplant of donor origin was engrafted. Following low-dose CsA, but not
      high-dose CsA treatment of the primary recipient, secondary transplants were
      accepted long-term in the absence of immunosuppression. Regulatory T-cell
      function was unimpaired and independent of the CyA dosage. Of note, low-dose CsA
      significantly reduced alloantibody titers in primary recipients. Adoptive
      transfer of graft infiltrating cells or splenocytes from hyporesponsive
      recipients supported long-term acceptance of donor kidney allografts. These
      results demonstrate a dose-dependent and transferable "pro-tolerogenic" effect of
      low-dose CsA treatment. This model is of clinical relevance to test the
      interference of CsA with tolerance induction in the absence of additional
      immunosuppression.

PMID- 22414757
TI  - Alkyl cinnamates as regulator for the C1 domain of protein kinase C isoforms.
AB  - The protein kinase C (PKC) family of serine/threonine kinases is an attractive
      drug target for the treatment of cancer and other diseases. Natural product
      curcumin is known to interact with PKC isoforms through the C1 domain and
      modulate PKC activity. The reported results demonstrate that the symmetric
      curcumin molecule might act as two separate units during its recognition of C1
      domains. To understand the importance of the two halves of curcumin in PKC
      binding and to develop effective PKC regulators, we synthesized a series of alkyl
      cinnamates (1-8), characterized absorption and fluorescence properties and
      measured binding affinities with the C1b subdomains of PKC isoforms. The binding
      parameters of the monomeric compounds and liposomes containing compounds
      confirmed their interaction with the C1b subdomains of PKCdelta and PKCtheta. The
      molecular docking analysis with PKCdelta and PKCtheta C1b subdomains revealed
      that the alkyl cinnamates form hydrogen bond with the backbone of the protein at
      the same binding site as that of diacylglycerol and phorbol esters. The results
      show that the alkyl cinnamates bind to the activator binding site of PKCs and
      both methoxy and hydroxyl groups play important roles in the binding process.

PMID- 22414758
TI  - Identification and analysis of two novel sites of rat GnRH receptor gene promoter
      activity: the pineal gland and retina.
AB  - BACKGROUND AND AIMS: In mammals, activation of pituitary GnRH receptor (GnRHR) by
      hypothalamic GnRH increases the synthesis and secretion of LH and FSH, which, in
      turn, regulate gonadal functions. However, GnRHR gene (Gnrhr) expression is not
      restricted to the pituitary. METHODS: To gain insight into the extrapituitary
      expression of Gnrhr, a transgenic mouse model that expresses the human placental
      alkaline phosphatase reporter gene driven by the rat Gnrhr promoter was created.
      RESULTS: This study shows that the rat Gnrhr promoter is operative in two
      functionally related organs, the pineal gland, as early as embryonic day (E)
      13.5, and the retina where activity was only detected at E17.5. Accordingly,
      Gnrhr mRNA were present in both tissues. Transcription factors known to regulate
      Gnrhr promoter activity such as the LIM homeodomain factors LHX3 and ISL1 were
      also detected in the retina. Furthermore, transient transfection studies in CHO
      and gonadotrope cells revealed that OTX2, a major transcription factor in both
      pineal and retina cell differentiation, is able to activate the Gnrhr promoter
      together with either CREB or PROP1, depending on the cell context. CONCLUSION:
      Rather than using alternate promoters, Gnrhr expression is directed to diverse
      cell lineages through specific associations of transcription factors acting on
      distinct response elements along the same promoter. These data open new avenues
      regarding GnRH-mediated control of seasonal and circadian rhythms in reproductive
      physiology.

PMID- 22414755
TI  - Transcription control by long non-coding RNAs.
AB  - Non-coding RNAs have been found to regulate many cellular processes and thus
      expand the functional genetic repertoire contained within the genome. With the
      recent advent of genomic tools, it is now evident that these RNA molecules play
      central regulatory roles in many transcriptional programs. Here we discuss how
      they are targeted to promoters in several cases and how they operate at specific
      points in the transcription cycle to precisely control gene expression.

PMID- 22414759
TI  - Associations between polymorphisms in genes involved in fatty acid metabolism and
      dietary fat intakes.
AB  - BACKGROUND: Obesity prevalence is growing in our population. Twin studies have
      estimated the heritability of dietary intakes to about 30%. The objective of this
      study was to verify whether polymorphisms in genes involved in fatty acid
      metabolism are associated with dietary fat intakes. METHODS: Seven hundred
      participants were recruited. A validated food frequency questionnaire was used to
      assess dietary intakes. PCR-RFLP and TAQMAN methodology were used to genotype
      PPARalpha Leu162Val, PPARgamma Pro12Ala, PPARdelta -87T>C, PPARGC1alpha
      Gly482Ser, FASN Val1483Ile and SREBF1 c.*619C>G. Statistical analyses were
      executed with SAS statistical package. RESULTS: Carriers of the Ala12 allele of
      PPARgamma Pro12Ala polymorphism had higher intakes of total fat (p = 0.04). For
      FASN Val1483Ile polymorphism, significant gene-sex interaction effects were found
      for total fat and saturated fat intakes (p = 0.02 and p = 0.002, respectively).
      No significant difference in fat intakes was observed for PPARalpha Leu162Val,
      PPARdelta -87T>C, PPARGC1alpha Gly482Ser and SREBF1 c.*619C>G polymorphisms.
      CONCLUSIONS: Polymorphisms in PPARgamma and FASN seem to be associated with
      dietary fat intakes. Genetic variants are important to take into account when
      studying dietary intakes.

PMID- 22414760
TI  - Usefulness of alpha-fetoprotein response in patients treated with sorafenib for
      advanced hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Tumor shrinkage has been considered a fundamental surrogate
      efficacy measure for new cancer treatments. However, in patients treated with
      sorafenib for advanced hepatocellular carcinoma (HCC), tumor shrinkage rarely
      accompanies increased survival, thereby questioning the prognostic value of
      imaging-based Response Evaluation Criteria in Solid Tumors (RECIST). We
      investigated the prognostic usefulness of a decrease in serum alpha-fetoprotein
      (AFP) and compared it to RECIST. METHODS: In HCC patients treated with sorafenib
      with baseline AFP >20 ng/ml, AFP response was defined as a >20% decrease in AFP
      during 8weeks of treatment. Patients were also assessed by RECIST and were
      categorized as having radiologically proven progressive disease or disease
      control (consisting of complete or partial responses and stable disease).
      Comparisons of survival by RECIST and AFP response were corrected for guarantee
      time bias by the landmark method. RESULTS: We evaluated 85 patients for AFP
      response, among them, 82 were also evaluated by RECIST. In the analysis of AFP
      response, 32 out of 85 patients (37.6%) were responders, whereas 58 out of 82
      patients (70.7%) achieved disease control. In landmark analysis, the hazard
      ratios (HR) for survival according to AFP response and disease control were 0.59
      (p=0.040) and 1.03 (p=0.913), respectively. In multivariate analysis, only AFP
      response (HR=0.52; p=0.009) and Cancer of the Liver Italian Program dichotomized
      stage (HR=0.42; p=0.002) were prognostic factors of survival. CONCLUSIONS:
      Assessment of AFP response may be considered as an alternative to RECIST to
      capture sorafenib activity in HCC.

PMID- 22414761
TI  - Apolipoprotein-E and hepatitis C lipoviral particles in genotype 1 infection:
      evidence for an association with interferon sensitivity.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) interacts with apolipoproteins B
      (apoB) and E (apoE) to form infectious lipoviral particles (LVP). Response to
      peginterferon is influenced by interferon-stimulated genes (ISGs) and IL28B
      genotype. LDL cholesterol (LDL-C) also predicts interferon response, therefore we
      hypothesised that LVP may also be associated with interferon sensitivity.
      METHODS: LVP (HCV RNA density <=1.07 g/ml) and 'non-LVP' (d >1.07 g/ml) were
      measured in 72 fasted HCV-G1 patients by iodixanol density gradient
      ultracentrifugation and the LVP ratio (LVP/LVP+non-LVP) was calculated. Fasting
      lipid profiles and apolipoproteins B and E were measured. Interferon-gamma
      inducible protein 10 kDa (IP10), a marker of ISGs, was measured by ELISA.
      RESULTS: Complete early virological response (EVR) was associated with lower apoE
      (23.9+/-7.7 vs. 36.1+/-15.3 mg/L, p=0.013), higher LDL-C (p=0.039) and lower LVP
      ratios (p=0.022) compared to null responders. In multivariate linear regression
      analysis, apoE was independently associated with LVP (R(2) 19.5%, p=0.003) and
      LVP ratio (p=0.042), and negatively with LDL-C (p<0.001). IP10 was significantly
      associated with ApoB (p=0.001) and liver stiffness (p=0.032). IL28B rs12979860 CC
      was associated with complete EVR (p=0.044), low apoE (CC 28+/-11 vs. CT/TT 35+/
      13 mg/L, p=0.048) and higher non-LVP (p=0.008). Logistic regression analysis
      indicated that patients with high LVP ratios were less likely to have EVR (odds
      ratio 0.01, p=0.018). CONCLUSIONS: In HCV-G1, interferon sensitivity is
      characterised by low LVP ratios and low apoE levels in addition to higher LDL-C
      and IL28B rs12979860 CC. Null-response is associated with increased LVP ratio.
      The association of apoE and LVP with peginterferon treatment response suggests
      that lipid modulation is a potential target to modify interferon sensitivity.

PMID- 22414762
TI  - Benefits associated with antiviral treatment in kidney allograft recipients with
      chronic hepatitis B virus infection.
AB  - BACKGROUND & AIMS: Hepatitis B virus (HBV) infection is more frequent in kidney
      recipients than in the general population with a higher rate of liver-related
      morbidity and mortality. We evaluated the benefit associated with HBV viral
      suppression by nucleos(t)ide analogues treatment in HBV-infected kidney
      recipients. METHODS: This retrospective study included 42 HBsAg-positive kidney
      recipients, 33 males, 9 females, median age 54 years, followed up during a mean
      of 15.4+/-11.8 years after kidney transplantation. Mean treatment duration by
      single or combined nucleos(t)ide analogues was 6.8+/-4.3 years. Fibrosis, before
      treatment, according to Metavir score was: F4 for 6 patients, F3 for 10, F2 for
      6, and F0-F1 for 20 patients. The primary end point, the patient survival, was
      defined as patient death or liver transplantation, the secondary end point was
      graft survival. RESULTS: HBV DNA at the last evaluation was undetectable (<12
      IU/ml) in 92.8% of patients. During the follow-up, 8 patients died (17.7%), death
      being related to hepatocellular carcinoma in 4 (9.5%), including 1 patient with
      baseline mild fibrosis, and to extrahepatic causes in 4. This mortality rate is
      strikingly lower than that previously reported in HBV-infected kidney recipients
      before oral antiviral therapies. Graft survival seems to be improved when
      compared to the former series. CONCLUSIONS: Suppression of HBV replication
      associated with nucleo(s)tide analogues treatment improves the survival of HBV
      infected kidney recipients. Viral suppression does not exclude regular follow-up
      given the risk of occurrence of hepatocellular carcinoma even in non-cirrhotic
      patients.

PMID- 22414763
TI  - Novel human SR-BI antibodies prevent infection and dissemination of HCV in vitro
      and in humanized mice.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV)-induced end-stage liver disease is
      currently the major indication for liver transplantation in the Western world.
      After transplantation, the donor liver almost inevitably becomes infected by the
      circulating virus and disease progression is accelerated in immune suppressed
      transplant patients. The current standard therapy, based on pegylated interferon
      and ribavirin, induces severe side effects and is often ineffective in this
      population. Therefore, new strategies to prevent graft re-infection are urgently
      needed. We have previously shown that monoclonal antibodies (mAbs) against the
      HCV co-receptor scavenger receptor class B type I (SR-BI/Cla1) inhibit infection
      by different HCV genotypes in cell culture. METHODS: Using phage display
      libraries, we have generated a large set of novel human mAbs against SR-BI and
      evaluated their effectiveness in preventing HCV infection and direct cell-to-cell
      spread in vitro and in vivo using uPA-SCID mice with a humanized liver. RESULTS:
      Eleven human monoclonal antibodies were generated that specifically recognize SR
      BI. Two antibodies, mAb8 and mAb151, displayed the highest binding and inhibitory
      properties and also interfered with direct cell-to-cell spread in vitro. Studies
      in humanized mice showed that both antibodies were capable of preventing HCV
      infection and could block intrahepatic spread and virus amplification when
      administered 3 days after infection. Interestingly, anti-SR-BI therapy was
      effective against an HCV variant that escaped the control of the adaptive immune
      response in a liver transplant patient. CONCLUSIONS: The anti-SR-BI mAbs
      generated in this study may represent novel therapeutic tools to prevent HCV re
      infection of liver allografts.

PMID- 22414764
TI  - Epidermal growth factor receptor and HER-3 restrict cell response to sorafenib in
      hepatocellular carcinoma cells.
AB  - BACKGROUND & AIMS: Sorafenib is the standard of care for the treatment of
      advanced hepatocellular carcinoma (HCC). However, primary and acquired resistance
      is observed in patients. We examined whether gefitinib, which inhibits both
      epidermal growth factor receptor (EGFR) and HER-3 phosphorylation, could improve
      HCC cell response to sorafenib. METHODS: Sorafenib and gefitinib were tested in
      HCC tumor xenografts and in sorafenib-sensitive and sorafenib-resistant HCC cell
      lines. Biomarkers relevant to the HER system were analyzed by Western blotting
      and ELISA. RNA interference was used to downregulate the HER system. Amphiregulin
      concentrations were measured by ELISA in sera from patients under sorafenib
      treatment. RESULTS: Sorafenib combined with gefitinib significantly inhibited
      tumor growth in mice and reduced cell viability in vitro compared to single
      agents. In cell lines cultured in 10% serum or treated with EGF, sorafenib alone
      inhibited phospho-STAT3 while it maintained or even increased phospho-ERK and/or
      phospho-AKT. The paradoxical effects of sorafenib were prevented by gefitinib or
      by downregulation of EGFR and HER-3 expression. In cells with acquired resistance
      to sorafenib, aberrant activation of EGFR/HER-3 receptors as well as
      overexpression of several EGFR ligands were observed. These enhanced
      autocrine/paracrine loops led to the constitutive activation of ERK and AKT and
      conferred increased sensitivity to gefitinib. Increased serum concentrations of
      amphiregulin were observed in 10 out of 14 patients under sorafenib treatment
      compared to baselines. CONCLUSIONS: Signaling pathways controlled by EGFR and HER
      3 restrict sorafenib effects both in naive and sorafenib-resistant HCC cells.
      Consequently, gefitinib cooperates with sorafenib to increase antiproliferative
      response and to prevent resistance.

PMID- 22414765
TI  - Bak deficiency inhibits liver carcinogenesis: a causal link between apoptosis and
      carcinogenesis.
AB  - BACKGROUND & AIMS: Hepatocyte apoptosis is a key feature of chronic liver disease
      including viral hepatitis and steatohepatitis. A previous study demonstrated that
      absence of the Bcl-2 family protein Mcl-1 led to increased hepatocyte apoptosis
      and development of liver tumors in mice. Since Mcl-1 not only inhibits the
      mitochondrial pathway of apoptosis but can also inhibit cell cycle progression
      and promote DNA repair, it remains to be proven whether the tumor suppressive
      effects of Mcl-1 are mediated by prevention of apoptosis. METHODS: We examined
      liver tumor development, fibrogenesis, and oxidative stress in livers of
      hepatocyte-specific knockout (KO) of Mcl-1 or Bcl-xL, another key antagonist of
      apoptosis in hepatocytes. We also examined the impact of additional KO of Bak, a
      downstream molecule of Mcl-1 towards apoptosis but not the cell cycle or DNA
      damage pathway, on tumor development, hepatocyte apoptosis, and inflammation.
      RESULTS: Bcl-xL KO led to a high incidence of liver tumors in 1.5-year-old mice,
      similar to Mcl-1 KO. Bcl-xL- or Mcl-1-deficient livers showed higher levels of
      TNF-alpha production and oxidative stress than wild-type livers at as early as 6
      weeks of age and oxidative DNA damage at 1.5 years. Deletion of Bak significantly
      inhibited hepatocyte apoptosis in Mcl-1 KO mice and reduced the incidence of
      liver cancer, coinciding with reduction of TNF-alpha production, oxidative
      stress, and oxidative DNA damage in non-cancerous livers. CONCLUSIONS: Our
      findings strongly suggest that chronically increased apoptosis in hepatocytes is
      carcinogenic and offer genetic evidence that inhibition of apoptosis may suppress
      liver carcinogenesis in chronic liver disease.

PMID- 22414766
TI  - Rapid and strong antiviral activity of the non-nucleosidic NS5B polymerase
      inhibitor BI 207127 in combination with peginterferon alfa 2a and ribavirin.
AB  - BACKGROUND & AIMS: BI 207127 is a potent non-nucleoside hepatitis C virus (HCV)
      NS5B polymerase inhibitor in vitro. METHODS: In this double-blind, placebo
      controlled study, 57 HCV genotype (GT)-1 patients (n=27 treatment-naive [TN];
      n=30 treatment-experienced [TE]) with compensated liver disease were randomised
      for 28-day treatment with 400, 600, or 800 mg BI 207127 three times daily (TID)
      or placebo (only TN) in combination with peginterferon alfa 2a and ribavirin
      (PegIFN/RBV). Plasma HCV RNA was measured by Roche COBAS TaqMan assay. RESULTS:
      HCV RNA decreased in a dose-dependent manner with little difference between 600
      mg (TN 5.6 log(10), TE 4.2 log(10)) and 800 mg (TN 5.4 log(10), TE 4.5 log(10)).
      Rapid virological response (RVR; HCV RNA <15 IU/ml) at day 28 occurred in 11/19
      TN and 4/30 TE patients treated with BI 207127. GT-1b patients had stronger
      reductions in HCV RNA than GT-1a (RVR: TN 64% vs. 43%; TE 33% vs. 5%). There were
      no breakthroughs (HCV RNA rebound >1 log(10) from nadir) in the TN groups,
      whereas 3/30 TE patients experienced breakthrough due to P495-mutations.
      Gastrointestinal adverse events (AEs) and rash were the major AEs and most
      frequent at higher doses. One and four patients discontinued due to AEs in the
      600 and 800 mg groups, respectively. Overall, tolerability was good and better at
      600 mg than 800 mg. CONCLUSIONS: BI 207127 in combination with PegIFN/RBV
      demonstrated strong antiviral activity with a favourable safety and tolerability
      profile. The best benefit/risk ratio was observed at 600 mg.

PMID- 22414767
TI  - Effect of ursodeoxycholic acid on bile acid profiles and intestinal
      detoxification machinery in primary biliary cirrhosis and health.
AB  - BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) exerts anticholestatic,
      antifibrotic and antiproliferative effects in primary biliary cirrhosis (PBC) via
      mechanisms not yet fully understood. Its adequate biliary enrichment is
      considered mandatory for therapeutic efficacy. However, precise determination of
      biliary enrichment of UDCA is not possible in clinical practice. Therefore, we
      investigated (i) the relationship between biliary enrichment and plasma
      pharmacokinetics of UDCA, (ii) the effect of UDCA on plasma and biliary bile acid
      composition and conjugation patterns, and (iii) on the intestinal detoxification
      machinery in patients with PBC and healthy controls. METHODS: In 11 PBC patients
      and 11 matched healthy subjects, cystic bile and duodenal tissue were collected
      before and after 3 weeks of administration of UDCA (15 mg/kg/day). Extensive
      pharmacokinetic profiling of bile acids was performed. The effect of UDCA on the
      intestinal detoxification machinery was studied by quantitative PCR and Western
      blotting. RESULTS: The relative fraction of UDCA and its conjugates in plasma at
      trough level[x] correlated with their biliary enrichment[y] (r=0.73, p=0.0001,
      y=3.65+0.49x). Taurine conjugates of the major hydrophobic bile acid,
      chenodeoxycholic acid, were more prominent in bile of PBC patients than in that
      of healthy controls. Biliary bile acid conjugation patterns normalized after
      treatment with UDCA. UDCA induced duodenal expression of key export pumps, BCRP
      and P-glycoprotein. CONCLUSIONS: Biliary and trough plasma enrichment of UDCA are
      closely correlated in PBC and health. Taurine conjugation may represent an
      adaptive mechanism in PBC against chenodeoxycholic acid-mediated bile duct
      damage. UDCA may stabilize small intestinal detoxification by upregulation of
      efflux pumps.

PMID- 22414768
TI  - Exercise and non-alcoholic fatty liver disease: a systematic review and meta
      analysis.
AB  - BACKGROUND & AIMS: Exercise is an integral component of lifestyle intervention
      aimed at weight loss, but an independent benefit of exercise in NAFLD has also
      been suggested. METHODS: We aimed to evaluate the efficacy of aerobic exercise
      and/or progressive resistance training for the modulation of liver fat and
      alanine aminotransferase (ALT) levels in adults. Relevant databases were searched
      up to August 2011 for controlled trials, which compared regular exercise vs. a
      non-exercise control on change in liver fat and/or ALT. RESULTS: Of the 16,822
      studies from the initial search, 12 were included. There was a significant pooled
      effect size (ES) for the comparison between exercise therapy vs. control (ES=
      0.37, 95% CI: -0.06 to -0.69; p=0.02), but only when interventions which compared
      combined exercise and diet vs. diet-alone and achieved substantial weight loss,
      were omitted. The benefit of exercise on liver fat occurred with minimal or no
      weight loss. There was no effect of exercise alone vs. control on ALT (ES=-0.15,
      95% CI: 0.14 to -0.45; p=0.32). CONCLUSIONS: Individual reports of exercise
      interventions often have low sample sizes and insufficient power to detect
      clinically meaningful hepatic benefits. By pooling current research, we show
      clear evidence for a benefit of exercise therapy on liver fat but not ALT levels.
      This benefit is apparent with minimal or no weight loss and at exercise levels
      below current exercise recommendations for obesity management. Given the paucity
      of current treatment options, exercise provides a valid, low-cost therapy for
      disorders characterised by fatty liver.

PMID- 22414769
TI  - Imparting permanent antimicrobial activity onto viscose and acrylic fabrics.
AB  - Viscose and acrylic fabrics were aminated to enhance metal chelation of Cu, Zn
      and Ni for the purpose of imparting fabrics antimicrobial activity against
      Escherichia coli and Staphylococcus aureus. Fabrics were firstly epoxidized using
      epichlorohydrin prior amination. Optimization of the reaction conditions, e.g.,
      temperature, medium pH, amine type and metal type and their concentrations, are
      reported. Aminated fabrics of viscose and acrylic were shown to be viable for
      chelation with divalent metal cations. The overall results revealed that
      antibacterial resistance of metalized aminated fabrics that the activity trend of
      metals is in the order Cu-complex>Zn-complex>Ni-complex with regard to fighting
      of microorganisms and permanent even after 10 washing. Reaction mechanism of
      epoxidation, amination and metal chelation of fabrics are offered supported by FT
      IR structural study, nitrogen content and atomic absorption spectroscopy.

PMID- 22414770
TI  - Reorganization of oscillatory activity in human parietal cortex during spatial
      updating.
AB  - Single-neuron recordings have shown that the posterior parietal cortex (PPC)
      processes spatial information in many frames of reference, including gaze
      centered, head-centered, body-centered, and intermediate coding frames. At the
      population level, rhythmic neuronal synchronization may provide a mechanism by
      which PPC could selectively emphasize the task-relevant reference frame in
      spatial processing. Using magnetoencephalography, we tested this hypothesis by
      studying the modulations in oscillatory activity in a spatial updating task.
      Human subjects had to remember the location of a target, briefly flashed left or
      right of central fixation. Next, they refixated and then, after a further memory
      delay, made a saccade to the memorized target location. We observed gamma-band
      (>40 Hz) synchronization and alpha-band (8-12 Hz) desychronization in
      contralateral occipital and parietal areas, both showing updating in a gaze
      centered reference frame but with fast and slow time courses, respectively.
      Furthermore, after updating, ipsilateral areas showed less alpha
      desynchronization when they had been contralateral to the target before updating.
      Taken together, our results suggest that power in the gamma band is instantly
      reorganized to encode task-relevant visuomotor space in a gaze-centered reference
      frame, while power in the alpha band reflects a regulatory mechanism actively
      facilitating the gating of the saccade target and inhibiting the original
      stimulus representation.

PMID- 22414771
TI  - Ependymal ciliary dysfunction and reactive astrocytosis in a reorganized
      subventricular zone after stroke.
AB  - Subventricular zone (SVZ) astrocytes and ependymal cells are both derived from
      radial glia and may have similar gliotic reactions after stroke. Diminishing SVZ
      neurogenesis worsens outcomes in mice, yet the effects of stroke on SVZ
      astrocytes and ependymal cells are poorly understood. We used mouse experimental
      stroke to determine if SVZ astrocytes and ependymal cells assume similar
      phenotypes and if stroke impacts their functions. Using lateral ventricular wall
      whole mount preparations, we show that stroke caused SVZ reactive astrocytosis,
      disrupting the neuroblast migratory scaffold. Also, SVZ vascular density and
      neural proliferation increased but apoptosis did not. In contrast to other
      reports, ependymal denudation and cell division was never observed. Remarkably,
      however, ependymal cells assumed features of reactive astrocytes post stroke,
      robustly expressing de novo glial fibrillary acidic protein, enlargening and
      extending long processes. Unexpectedly, stroke disrupted motile cilia planar cell
      polarity in ependymal cells. This suggested ciliary function was affected and
      indeed ventricular surface flow was slower and more turbulent post stroke.
      Together, these results demonstrate that in response to stroke there is
      significant SVZ reorganization with implications for both pathophysiology and
      therapeutic strategies.

PMID- 22414773
TI  - Protein synthesis in gilthead sea bream: response to partial fishmeal
      replacement.
AB  - The present study aimed to measure tissue protein synthesis in sea bream fed
      isonitrogenous diets that contained 63, 55 and 50 % fishmeal; in the latter two
      diets, 16 and 27 % of the fishmeal protein was replaced with plant protein. Over
      a 35 d period, there were no differences in feed intake, growth or feed
      efficiency among the three diets. Protein metabolism was then measured in the
      liver and white muscle tissue as rates of protein synthesis and as the capacity
      for protein synthesis before feeding (0 h) and at different times after feeding
      (4-48 h). Diet did not have a significant effect on protein synthesis or on the
      capacity for protein synthesis in either tissue. The capacity for protein
      synthesis was not affected by time after feeding, and overall mean values were
      81.02 (se 1.68) and 4.07 (se 0.94) mg RNA/g protein for the liver and white
      muscle, respectively. Liver and white muscle fractional rates of protein
      synthesis were significantly higher at 4-8 h, intermediate at 12 h and were not
      different among pre-feeding (0 h), 24 and 48 h. Overall, the indices of protein
      metabolism measured at various times over 48 h following feeding were closely
      aligned with measurements of feeding, growth and growth efficiency established
      over a longer time scale.

PMID- 22414772
TI  - The "what" and "when" of self-initiated movements.
AB  - The ability to generate intentional behavior is undeniably at the core of what
      makes us acting subjects. Intentional actions consist of at least 2 components
      (Brass M, Haggard P. 2008. The what, when, whether model of intentional action.
      Neuroscientist. 14:319-325.): choosing an appropriate behavior (what) and
      selecting the moment of execution (when). The aim of this study was to identify
      differing and overlapping neural networks underlying the "what" and "when" of
      intentional movement initiation. While scanned with functional magnetic resonance
      imaging, 35 healthy subjects performed self-initiated and reactive, that is,
      internally and externally triggered movements of the right or left index finger
      in 3 experimental conditions: 1) "Free Choice" (free timing: when/choice of hand:
      what), 2) "Timed Choice" (external timing/choice of hand: what), and 3) "No
      Choice" (external timing/cued hand). The what-component specifically employed the
      presupplementary motor area (SMA) and dorsal premotor cortex bilaterally. The
      when-network consisted of superior SMA together with insula and Area 44
      bilaterally as well as bilateral anterior putamen, globus pallidus, and left
      cerebellum subcortically. These 2 components recruited different networks,
      pointing to a partially distinct neuronal realization of the relating functions.
      Finally, the more intentional components were involved, the higher was activity
      in the anterior midcingulate cortex, which highlighted its role in intentional
      initiation of behavior.

PMID- 22414774
TI  - Long term metabolic impact of high protein neonatal feeding: a preliminary study
      in male rat pups born with a low birth weight.
AB  - BACKGROUND & AIMS: Nutrition received in early life may impact adult health. The
      aim of the study was to determine whether high protein feeding in neonatal period
      would have long term metabolic effects in an animal model of low birth weight
      infants. METHODS: Male rat pups born from dams receiving a low protein diet
      during gestation were separated from their mothers, and equipped with gastrostomy
      tubes to receive as their sole feeding a milk formula of either adequate protein
      (AP; n = 14; 8.7 g protein/dL; total energy: 155 kcal/100 g), or high protein
      content (HP; n = 14; 13.0 g protein/dL; total energy: 171 kcal/100 g) between the
      7th (D7) and 21st day (D21) of life. Rats were then weaned to standard chow until
      sacrificed at adulthood. RESULTS: At D18, HP feeding was associated with higher
      estimated rates of protein turnover (p = 0.007) and synthesis (p = 0.051), as
      assessed using l-[U-(13)C]valine infusion. HP milk feeding in early life was
      associated with an increase in weight gain from puberty through adulthood, along
      with an increase in food intake, serum insulin (179 +/- 58 vs. 55 +/- 7 pmol/L;
      means +/- SE), pancreatic beta-cell number, plasma triglycerides (95 +/- 8 vs. 73
      +/- 9 mg/dL), serum leptin (9.7 +/- 1.0 vs. 5.5 +/- 1.2 ng/mL), mesenteric fat
      mass, and adipocyte size. CONCLUSIONS: In an animal model of low birth weight
      infants, high protein neonatal feeding may have a lasting effect on fat and
      glucose metabolism, potentially leading to "metabolic syndrome" in adulthood.

PMID- 22414775
TI  - Sarcopenia as a risk factor for falls in elderly individuals: results from the
      ilSIRENTE study.
AB  - BACKGROUND & AIMS: Sarcopenia has been indicated as a reliable marker of frailty
      and poor prognosis among the oldest individuals. We evaluated the relationship
      between sarcopenia and 2-year risk of falls in a population of persons aged 80
      years or older. METHODS: Data are from the baseline and follow-up evaluations of
      the Aging and Longevity Study in the Sirente Geographic Area (ilSIRENTE Study)
      (n=260). According to the European Working Group on Sarcopenia in Older People
      (EWGSOP), sarcopenia was diagnosed in presence of low muscle mass (mid-arm muscle
      circumference) plus either low muscle strength (hand grip) or low physical
      performance (4-m walking speed). The primary outcome measure was the incident
      falls during the follow-up period of 2 years. The relationship between sarcopenia
      and incident falls was estimated by deriving hazard ratios (HRs) from multiple
      logistic regression models considering the dependent variable of interest at
      least one fall during the follow-up period. RESULTS: Sixty-six participants
      (25.4%) were identified as affected by sarcopenia. Eighteen out of 66 (27.3%)
      participants with sarcopenia and 19 out of 194 (9.8%) without sarcopenia reported
      incident falls during the two-year follow-up of the study (p<0.001). After
      adjusting for age, gender, cognitive impairment, ADL impairment, sensory
      impairments, BMI, depression, physical activity, cholesterol, stroke, diabetes,
      number of medications, and C-reactive protein, participants with sarcopenia had a
      higher risk of incident falls compared with non sarcopenic subjects (adjusted
      hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.25-8.29). CONCLUSIONS:
      The present study suggests that sarcopenia - assessed using the EWGSOP algorithm 
      is highly prevalent among elderly persons without gender differences (25%).
      Sarcopenic participants were over three times more likely to fall during a follow
      up period of 2 years relative to non sarcopenic individuals, regardless of age,
      gender and other confounding factors.

PMID- 22414776
TI  - Vitamin D status in healthy Romanian caregivers and risk of respiratory
      infections.
AB  - OBJECTIVES: To investigate the vitamin D status during winter of a healthy
      population of hospital employees and to assess the correlation between vitamin D
      status and risk of infections in the upper respiratory tract. DESIGN: One hundred
      and ten healthy volunteers answered a questionnaire on their solar exposure
      habits and vitamin D intake and delivered one blood sample for quantification of
      vitamin D level (serum 25-hydroxyvitamin D (25(OH)D) concentration) during
      December 2007-January 2008. At the end of the winter we screened for the
      occurrence of respiratory infections and sought associations with vitamin D
      status. SETTING: Bucharest, Romania, 45 degrees N. SUBJECTS: One hundred and ten
      healthy hospital employees. RESULTS: Eighty per cent of participants were vitamin
      D deficient (25(OH)D level below 50 nmol/l). The main determinant of serum
      25(OH)D was sun exposure during the summer previous to the study (P = 0.02 in
      multivariate analysis). Intake of vitamin D, BMI and age played no significant
      role for the level of 25(OH)D. Overall we found a non-significant negative
      correlation between 25(OH)D level and new cases of infection (Spearman
      correlation coefficient of -0.12, P = 0.2). CONCLUSIONS: Vitamin D status is
      alarmingly poor in active, relatively young women residing in Romania. If our
      results are reproduced by other investigations, action to improve vitamin D
      status at the population level is necessary. We were not able to show a
      statistically significant relationship between vitamin D status and infection
      risk in our material.

PMID- 22414777
TI  - Levels of heat shock protein 27 in placentae from small for gestational age
      newborns.
AB  - BACKGROUND/AIM: Recent data suggest that hsp27, a low-molecular-weight heat shock
      protein, exerts important cellular actions, including the modulation of oestrogen
      action. We investigated whether hsp27 was differentially expressed in placental
      samples from small for gestational age (SGA) neonates. METHODS: This study was
      performed in an academic hospital. Samples of villous tissue were obtained from
      placentae of 31 SGA (n = 16) or adequate to gestational age neonates (n = 15)
      delivered vaginally. The histological distribution of hsp27 in placental villi
      was investigated by immunohistochemistry, and the concentration of the protein
      was quantified by ELISA. Differences between groups were assessed by the
      nonparametric Mann-Whitney U test. RESULTS: Specific staining for hsp27 was
      detected in trophoblastic cells in most of the villi. The levels of hsp27 were
      lower in placentae from SGA neonates than from adequate to gestational age
      neonates. CONCLUSION: The expression of hsp27 was reduced in placentae from SGA
      neonates. Further work is required in order to clarify the role of hsp27 in
      placental physiology.

PMID- 22414780
TI  - Thermoregulatory aspects of performance.

PMID- 22414781
TI  - Effects of a toxic cyanobacterial bloom (Planktothrix agardhii) on fish: insights
      from histopathological and quantitative proteomic assessments following the oral
      exposure of medaka fish (Oryzias latipes).
AB  - Cyanobacterial toxic blooms often occur in freshwater lakes and constitute a
      potential health risk to human populations, as well as to fish and other aquatic
      organisms. Microcystin-LR (the cyanotoxin most commonly detected in the
      freshwater environment) is a potent hepatotoxin, deregulating the kinase pathway
      by inhibiting phosphatases 1 and 2A. Although toxicological effects have been
      clearly linked to the in vitro exposure of fish to purified microcystins,
      cyanotoxins are produced by the cyanobacteria together with numerous other
      potentially toxic molecules, and their overall and specific implications for the
      health of fish have still not been clearly established and remain puzzlingly
      difficult to assess. The medaka fish (Oryzias latipes) was chosen as an in vitro
      model for studying the effects of a cyanobacterial bloom on liver protein
      contents using a gel free quantitative approach, iTRAQ, in addition to pathology
      examinations on histological preparations. Fish were gavaged with 5 MUL
      cyanobacterial extracts (Planktothrix agardhii) from a natural bloom (La Grande
      Paroisse, France) containing 2.5 MUg equiv. MC-LR. 2h after exposure, the fish
      were sacrificed and livers were collected for analysis. Histological observations
      indicate that hepatocytes present glycogen storage loss, and cellular damages,
      together with immunological localization of MCs. Using a proteomic approach, 304
      proteins were identified in the fish livers, 147 of them with a high degree of
      identification confidence. Fifteen of these proteins were statistically
      significantly different from those of controls (gavaged with water only).
      Overall, these protein regulation discrepancies clearly indicate that oxidative
      stress and lipid regulation had occurred in the livers of the exposed medaka
      fish. In contrast to previous pure microcystin-LR gavage experiments, marked
      induction of vitellogenin 1 protein was observed for the first time with a
      cyanobacterial extract. This finding was confirmed by ELISA quantification of
      vitellogenin liver content, suggesting that the Planktothrix bloom extract had
      induced the occurrence of an endocrine-disrupting effect.

PMID- 22414783
TI  - Erbium emission in MOS light emitting  devices: from energy transfer to direct 
      impact excitation.
AB  - The electroluminescence (EL) at 1.54 MUm of metal-oxide-semiconductor (MOS)
      devices withEr3C ions embedded in the silicon-rich silicon oxide (SRSO) layer has
      been investigated under different polarization conditions and compared with that
      of erbium doped SiO2 layers. EL time-resolved measurements allowed us to
      distinguish between two different excitation mechanisms responsible for the Er3C
      emission under an alternate pulsed voltage signal (APV). Energy transfer from
      silicon nanoclusters (Si-ncs) to Er3C is clearly observed at low-field APV
      excitation. We demonstrate that sequential electron and hole injection at the
      edges of the pulses creates excited states in Si-ncs which upon recombination
      transfer their energy to Er3C ions. On the contrary, direct impact excitation of
      Er3C by hot injected carriers starts at the Fowler-Nordheim injection threshold
      (above 5 MV cm(-1)) and dominates for high-field APV excitation.

PMID- 22414784
TI  - Does body mass index influence the outcomes of a Waking-based pulmonary
      rehabilitation programme in COPD?
AB  - Body mass index (BMI) is an important prognostic measure in chronic obstructive
      pulmonary disease (COPD). However, its effects on pulmonary rehabilitation (PR)
      are unknown. This study aimed to evaluate the effectiveness of a walking-based PR
      programme across the BMI range and the impact of BMI on exercise performance and
      health status. A total of 601 patients with COPD completed a PR programme. The
      effects of BMI on exercise capacity (incremental and endurance shuttle walk tests
      (ISWT and ESWT)) and health status (chronic respiratory questionnaire (CRQ))
      before and after PR were evaluated. 16% of patients were underweight, with 53%
      overweight or obese. At baseline, the obese had worse ISWT (-54 m +/- 14 m; p =
      0.001) despite a higher predicted forced expiratory volume in 1 s (7.4m +/- 1.6%;
      p < 0.001). Patients in all BMI categories made clinically important improvements
      in ISWT distance: BMI <21, 62 m; 21-25, 59 m; 25-30, 59 m; >30, 65 m (p = <
      0.001). All four domains of the CRQ increased above the level of clinical
      significance for all BMI categories (all p < 0.001). The majority of patients
      with COPD were overweight associated with a lower walking capacity. A walking
      based PR programme was comparably effective across the BMI spectrum. Patients
      with COPD should be referred for standard PR, independent of BMI.

PMID- 22414785
TI  - Vitamin D actions to regulate calcium and skeletal homeostasis.
AB  - The endocrine action of plasma 1,25-dihydroxyvitamin D plays a key role in the
      regulation of plasma calcium and phosphate homeostasis with activities on the
      intestine, kidney and bone. A current, controversial question is whether vitamin
      D exerts direct actions on bone cells to regulate bone mineral homeostasis.
      Results from clinical, rodent model and in vitro studies on human bone cells
      provide an impressive body of data to support this proposal particularly at the
      level of serum 25-hydroxyvitamin D status. Each of the major bone cell types is
      capable of metabolising vitamin D to the active metabolite, 1,25-dihydroxyvitamin
      D. Thus under conditions when bone tissue synthesis of 1,25-dihydroxyvitamin D is
      optimal, vitamin D activity enhances bone mineral status. Dietary calcium and
      phosphate intakes are the critical environmental cues together with vitamin D
      status to determine whether 1,25-dihydroxyvitamin D exerts an anabolic or
      catabolic action on bone mineral status.

PMID- 22414786
TI  - Potential utility of resting-state magnetoencephalography as a biomarker of CNS
      abnormality in HIV disease.
AB  - There is a lack of a neuroimaging biomarker for HIV-Associated Neurocognitive
      Disorder. We report magnetoencephalography (MEG) data from patients with HIV
      disease and risk-group appropriate controls that were collected to determine the
      MEG frequency profile during the resting state, and the stability of the profile
      over 24 weeks. 17 individuals (10 HIV+, 7 HIV-) completed detailed
      neurobehavioral evaluations and 10min of resting-state MEG acquisition with a 306
      channel whole-head system. The entire evaluation and MEG measurement were
      repeated 24 weeks later. Relative MEG power in the delta (0-4Hz), theta (4-7Hz),
      alpha (8-12Hz), beta (12-30Hz) and low gamma (30-50Hz) bands was computed for 8
      predefined sensor groups. The median stability of resting-state relative power
      over 24 weeks of follow-up was .80 with eyes closed, and .72 with eyes open. The
      relative gamma power in the right occipital (t(15)=1.99, p<.06, r=-.46) and right
      frontal (t(15)=2.15, p<.05, r=-.48) regions was associated with serostatus. The
      effect of age on delta power was greater in the seropositive subjects (r(2)=.51)
      than in the seronegative subjects (r(2)=.11). Individuals with high theta-to
      gamma ratios tended to have lower cognitive test performance, regardless of
      serostatus. The stability of the wide-band MEG frequency profiles over 24 weeks
      supports the utility of MEG as a biomarker. The links between the MEG profile,
      serostatus, and cognition suggest further research on its potential in HAND is
      needed.

PMID- 22414787
TI  - Sweet and salty. An assessment of the snacks and beverages sold in vending
      machines on US post-secondary institution campuses.
AB  - This study assessed the nutritional quality of snacks and beverages sold in
      vending machines. The contents of snack and beverage vending machines in 78
      buildings on 11 US post-secondary education campuses were surveyed. Of the 2607
      snack machine slots surveyed, the most common snacks vended were salty snacks
      (e.g., chips, pretzels) and sweets (i.e., candy and candy bars). The 1650
      beverage machine slots assessed contained twice as many sugar-sweetened beverages
      as non-calorie-containing beverages. Only two institutions sold both milk and
      100% juice in vending machines. The portion of snacks and beverages sold averaged
      more than 200 cal. Neither snacks nor beverages were nutrient dense. The majority
      of snacks were low in fiber and high in calories and fat and almost half were
      high in sugar. Most beverages were high in calories and sugar. This study's
      findings suggest that vending machines provide limited healthful choices.
      Findings from benchmark assessments of components of the food environment, like
      the vending options reported here, can provide valuable input to campus
      administrators, health services, food service, and students who want to establish
      campus policies to promote healthful eating.

PMID- 22414788
TI  - Evaluating the difference in preventive vaccination uptake in patients with
      diabetes mellitus.

PMID- 22414789
TI  - Comment: Neuroleptic malignant syndrome versus serotonin syndrome: the search for
      a diagnostic tool.

PMID- 22414782
TI  - 8OHdG as a marker for Huntington disease progression.
AB  - Leukocyte 8-hydroxydeoxyguanosine (8OHdG) is an indicator of oxidative stress,
      impaired metabolism, and mitochondrial dysfunction, features that have been
      implicated in Huntington disease (HD). Increased levels of 8OHdG have been
      reported in the caudate, parietal cortex, and peripherally in the serum and
      leukocytes, in patients diagnosed with HD. However, little is known about levels
      in prodromal patients and changes that might occur as the disease progresses. To
      address these issues, 8OHdG was tracked over time for a subset of participants
      enrolled in the PREDICT-HD study. Participants were stratified into four groups
      based on proximity to HD diagnosis at study entry: Controls (gene-negative
      individuals), Low (low probability of near-future diagnosis), Medium, and High.
      Blood samples were analyzed using Liquid Chromatography Electrochemical Array,
      and for comparison purposes, a separate cross-sectional sample was analyzed using
      liquid chromatography coupled with multiple-reaction-monitoring mass
      spectrometry. Longitudinal data analysis showed that initial status (at study
      entry) and annual rate of change varied as a function of proximity group,
      adjusting for sex, education, age at study entry, and site effects. Overall
      levels were lowest for the Control group and highest for the High group, and the
      rate of increase varied in a similar manner. The finding that 8OHdG
      concentrations increased as a function of proximity to projected disease
      diagnosis and duration indicates support for the continued assessment of 8OHdG as
      a robust clinical HD biomarker.

PMID- 22414792
TI  - Comment: Neuroleptic malignant syndrome versus serotonin syndrome: the search for
      a diagnostic tool.

PMID- 22414791
TI  - Cholinesterase inhibitor adjunctive therapy for cognitive impairment and
      depressive symptoms in older adults with depression.
AB  - OBJECTIVE: To review the primary literature regarding the use of cholinesterase
      inhibitors (ChEIs) as adjunctive therapy for cognitive enhancement and
      improvement of depressive symptoms for older adults with depression. DATA
      SOURCES: A literature search of MEDLINE (1950-September 2011) was conducted,
      using the search term depression in combination with cholinesterase inhibitor,
      donepezil, galantamine, or rivastigmine. A search of reference citations was
      conducted to identify additional references. STUDY SELECTION AND DATA EXTRACTION:
      English-language clinical trials were evaluated. Studies that included subjects
      with Alzheimer's disease, dementia, Parkinson disease, bipolar disorder, or
      schizophrenia were excluded. Four clinical studies met our criteria. DATA
      SYNTHESIS: We identified 4 randomized, double-blind, placebo-controlled trials
      that ranged in sample size from 20 to 130. Galantamine 16 mg daily was evaluated
      in 2 trials lasting 8 and 24 weeks. Neither study found a statistically
      significant difference in measures of cognition or Hamilton Rating Scale for
      Depression scores. Donepezil augmentation was evaluated in a 1-year and a 2-year
      trial. Donepezil was found to improve global cognition at 1 year, but the benefit
      did not persist at year 2. Subjects with mild cognitive impairment at baseline
      who received donepezil experienced higher depression recurrence than did those
      who took placebo (p = 0.03); this effect was not observed in cognitively intact
      subjects (p = 0.39). CONCLUSIONS: There is no clear benefit for ChEI therapy as
      an adjunct to antidepressant therapy for depressed older adults.

PMID- 22414793
TI  - Effect of medication reconciliation at hospital admission on medication
      discrepancies during hospitalization and at discharge for geriatric patients.
AB  - BACKGROUND: Medication discrepancies have the potential to cause harm. Medication
      reconciliation by clinical pharmacists aims to prevent discrepancies and other
      drug-related problems. OBJECTIVE: To determine how often discrepancies in the
      physician-acquired medication history result in discrepancies during
      hospitalization and at discharge. Secondary objectives were to determine the
      influence of clinical pharmacists' interventions on discrepancies and to
      investigate possible patient-related determinants for experiencing discrepancies.
      METHODS: This was a retrospective, single-center, cohort study of patients who
      were admitted to the acute geriatric department of a Belgian university hospital
      and followed up by clinical pharmacists between September 2009 and April 2010.
      Patients were limited to those 65 years or older who were taking 1 or more
      prescription drug. Medication reconciliation at admission, during
      hospitalization, and at discharge was conducted by an independent pharmacist who
      gathered information via chart reviews. RESULTS: The reconciliation process at
      admission identified 681 discrepancies in 199 patients. Approximately 81.9% (163)
      of patients had at least 1 discrepancy in the physician-acquired medication
      history. The clinical pharmacists performed 386 interventions, which were
      accepted in 279 cases (72.3%). A quarter of the medication history discrepancies
      (165; 24.2%) resulted in discrepancies during hospitalization, mostly because the
      intervention was not accepted. At discharge, 278 medication history discrepancies
      (40.8%) resulted in discrepancies in the discharge letter, accounting for 50.2%
      of all 554 discrepancies identified in the discharge letters. The likelihood for
      experiencing discrepancies at admission increased by 47% for every additional
      drug listed in the medication history. CONCLUSIONS: Discrepancies in the
      physician-acquired medication history at admission do not always correlate with
      discrepancies during hospitalization because of clinical pharmacists'
      interventions; however, discrepancies at admission may be associated with at
      least half of the discrepancies at discharge. Clinical pharmacist-conducted
      medication reconciliation can reduce these discrepancies, provided the erroneous
      information in the physician-acquired medication history is corrected and each
      intentional change in the medication plan is well documented during
      hospitalization and at discharge.

PMID- 22414794
TI  - Quality of clinical trials in gastroenteropancreatic neuroendocrine tumours.
AB  - BACKGROUND: The heterogeneity of neuroendocrine tumours (NETs) makes
      interpretation of clinical trials in this disease challenging. Our aim was to
      review the quality of treatment trials in NETs in order to inform the design and
      reporting of future studies. METHODS: We identified studies by searching MEDLINE.
      We considered all phase II and III trials of systemic antineoplastic treatments
      published between 2000 and 2011. Information on trial design, study population,
      end points, statistical considerations and results was abstracted from each
      article using a standardized form. RESULTS: Seven phase III and 39 phase II
      trials were identified. The make-up of the study population was variable: only
      24% of trials included patients with one type of tumour (pancreatic NET or
      carcinoid tumour), 41% included patients with both tumour types, and 35% of
      trials included other endocrine cancers. Disease progression at baseline was
      often not reported and was documented for all patients in 22% of the trials. The
      functional status of the tumour, tumour differentiation, and Ki67 index were
      reported in 35, 43, and 15% of trials, respectively. The primary end point was
      clearly defined in 72% of trials. Identifiable statistical design, and predefined
      sample size were reported in 74 and 61% of trials, respectively. Conflicts of
      interest and study sponsorship were reported in 46 and 85% of trials.
      CONCLUSIONS: The quality of the design and reporting of phase II/III NET trials,
      as described in other cancers, is poor. Future trials should include more
      homogenous patient populations while adhering to rigorous selection, reporting
      and interpretation of population and trial parameters.

PMID- 22414795
TI  - Feedback networks between microRNAs and epigenetic modifications in urological
      tumors.
AB  - Epigenetic modifications and microRNAs are known to play key roles in human
      cancer. For urological tumors, changes in epigenetic modifications and aberrant
      microRNA profiles have been reported. However, the mechanisms of epigenetic and
      microRNA regulation are not entirely separable. Increasingly, recent research in
      these fields overlaps. There seems to be a complicated feedback interrelationship
      between epigenetic and microRNA regulation that must be highly controlled.
      Disruptions of this feedback network can have serious consequences for various
      biological processes and can result in cellular transformation. Investigation of
      the network between microRNAs and epigenetics could lead to a better
      understanding of the processes involved in development and progression of
      urological tumors. This understanding could provide new approaches for the
      development of novel individualized therapies, which are adjusted to the
      molecular pattern of a tumor. In this review, we present an overview of microRNA
      epigenetic circuits acting in urological tumors.

PMID- 22414797
TI  - Discussing epigenetics in Southern California: a report from the International
      Symposium on Epigenetic Control and Cellular Plasticity, UCI, December 15-16,
      2011.
AB  - With the goal of discussing how epigenetic control and chromatin remodeling
      contribute to the various processes that lead to cellular plasticity and disease,
      this symposium marks the collaboration between the Institut National de la Sante
      et de la Recherche Medicale (INSERM) in France and the University of California,
      Irvine (UCI). Organized by Paolo Sassone-Corsi (UCI) and held at the Beckman
      Center of the National Academy of Sciences at the UCI campus December 15-16,
      2011, this was the first of a series of international conferences on epigenetics
      dedicated to the scientific community in Southern California. The meeting also
      served as the official kick off for the newly formed Center for Epigenetics and
      Metabolism at the School of Medicine, UCI (http://cem.igb.uci.edu).

PMID- 22414798
TI  - Biostructural theory of the living systems.
AB  - Eugen Macovschi is among the few scientists who tried, and partly succeeded, to
      explain the differences between "dead" and "living" in biological sciences. He
      discovered and characterized the so-called biostructure of the living bodies and
      worked out a biostructural theory, which is the first supramolecular conception
      in biology. Nevertheless, complex biological systems are currently considered
      only from the molecular point of view, although they may be regarded as specific
      phenomena on highly structured bodies within the four-dimensional Universe.
      According to Macovschi, the biostructure provides organisms with life properties
      and controls their life processes and chemical changes. Nevertheless, plant cells
      or bacterial ones differ much from the animal or human cells. In fact, there are
      various biostructures which are related with cell properties. Hence, this theory
      creates confusions and cannot be easily used to explain all the properties of the
      biosystems. Consequently, it is our goal to highlight the principles, advantages,
      limitations, and applications of the biostructural theory, which might support
      new ideas and theories in modern life sciences.

PMID- 22414799
TI  - Parents' misperceptions of social norms for pre-school children's snacking
      behaviour.
AB  - OBJECTIVE: Misperception of social norms may result in normalising unhealthy
      behaviours. The present study tested the hypothesis that parents overestimate
      both the frequency of unhealthy snacking in pre-school children other than their
      own (descriptive norms) and its acceptability to other parents (injunctive
      norms). DESIGN: A cross-sectional, self-report community survey. Questions
      assessed the frequency with which respondents' own child ate unhealthy snacks and
      their beliefs about the appropriate frequency for children to snack. Perceived
      descriptive norms were assessed by asking parents to estimate how often other 2-4
      year-old children in their area ate snacks. Perceived injunctive norms were
      assessed by asking them about other parents' beliefs regarding the appropriate
      frequency for snacks. Misperceptions were assessed from (i) the difference
      between the prevalence of daily snacking and parents' perceived prevalence and
      (ii) the difference between acceptability of daily snacking and parents' beliefs
      about its acceptability to others. SETTING: Pre-schools and children's centres in
      one borough of London, UK. SUBJECTS: Parents (n 432) of children age 2-4 years.
      RESULTS: On average, parents believed that more than half of 'other' children had
      snacks at least daily, while prevalence data indicated this occurred in only 10 %
      of families. The same discrepancy was observed for perceived injunctive norms:
      parents overestimated other parents' acceptance of frequent snacking, with two
      thirds of parents having a self v. others discrepancy. CONCLUSIONS:
      Misperceptions were identified for descriptive and injunctive norms for
      children's snacking. Accurate information could create less permissive norms and
      motivate parents to limit their child's intake of unhealthy snacks.

PMID- 22414800
TI  - Palinacousis--evidence to suggest a post-ictal phenomenon.
AB  - INTRODUCTION: Palinacousis is a paroxysmal auditory illusion in which
      perseveration of an external auditory stimulus occurs after cessation of the
      stimulus. The subjects recognize the illusory nature of this experience, which is
      often a fragment of the last sentence they heard. Palinacousis has been reported
      in only a few documented cases. It has been described as an aura, a component of
      complex partial seizures, and a post-ictal event. We put forward evidence
      demonstrating palinacousis as a post-ictal event. CASE: A 68-year-old woman
      presented with an acute sensory aphasia, and an EEG showed frequent epileptiform
      discharges from the left temporo-parietal region. MRI showed an enhancing mass in
      the left inferior parietal lobule that was consistent with a metastasis. A CT
      scan of the thorax later showed an enhancing mass in the left lung that was
      determined to be an invasive non-small cell carcinoma. Treatment with
      levetiracetam resulted in loss of epileptiform activity on EEG and resolution of
      aphasia, but soon afterward, she started complaining of recurrent auditory
      illusions in her right ear. These consisted of phrases from the ends of sentences
      she heard. Continuous EEG monitoring during her auditory symptoms showed
      intermittent left temporal slowing but no epileptiform discharges or
      electrographic seizures. An FDG-PET scan with the glucose uptake phase during
      episodes of auditory illusions revealed hypometabolism of bilateral medial
      temporal cortices and increased uptake in the metastatic tumor. REVIEW OF
      LITERATURE: A systematic review identified 14 cases with palinacousis since 1981.
      Cases prior to that were excluded due to the lack of sufficient data. DISCUSSION:
      We propose that palinacousis is a "negative" phenomenon, at least in some
      individuals. It occurs with a loss of function of a region of the brain that
      normally suppresses auditory perseveration.

PMID- 22414801
TI  - Ion specific influences on the stability and unfolding transitions of a naturally
      aggregating protein; RecA.
AB  - The Escherichia coli RecA protein is a naturally aggregated protein complex that
      is affected by the presence of salts. In order to gain further insight into the
      nature of the ion-interactions on a naturally aggregating protein we used
      circular dichroism (CD), fluorescence and dynamic light scattering (DLS) to study
      the effects of different concentrations of MgCl2, CaCl2, NaCl, Na2SO4, and MgSO4
      on RecA structure and thermal unfolding. The results show unique ion influences
      on RecA structure, aggregation, unfolding transitions and stability and the anion
      effects correlate with the reverse Hofmeister series. The mechanisms of the ion
      induced changes most likely result from specific ion binding, changes in the
      interfacial tension and altered protein-solvent interactions that may be
      especially important for protein-protein interactions in naturally aggregating
      proteins. The presence of some ions leads to the formation of RecA complexes that
      are resistant to complete denaturation and nonspecific aggregation.

PMID- 22414802
TI  - Utilizing genomic polymorphisms to personalize hepatitis C therapies.
AB  - PURPOSE OF REVIEW: The need for liver transplant due to the progression of
      hepatitis C virus (HCV) infection necessitates the consideration of antiviral
      treatment. Host genomic variations affect response to HCV treatment and predict
      the rates of adverse effects. Recently, multiple genomic polymorphisms were found
      to be critical in predicting treatment response as well as the rate of
      neuropsychiatric adverse effects in patients infected with HCV who are receiving
      antiviral treatments. RECENT FINDINGS: The use of antiviral treatments (pegylated
      IFN-alpha and ribavirin) to clear HCV infection is associated with poor response
      in HCV genotype 1 and with the development of depression. Polymorphisms in the
      promoter region of the IFN-alpha/beta receptor 1 (IFNAR1) can influence the risk
      of developing depression. Similar polymorphisms in the IL28B gene encoding for
      IFN-lambda-3 are associated with a two- to three-fold improvement in response to
      treatment. SUMMARY: In patients with HCV infection receiving antiviral
      treatments, genomic variations in two genes can help predict the increased risk
      of developing depression and the likelihood of achieving virus clearance. This
      can identify patients who are at an increased likelihood of virus clearance and
      who should be targeted to receive prophylactic approaches (antidepressants,
      psychotropics) to prevent the development of depression during HCV antiviral
      treatment.

PMID- 22414804
TI  - In pursuit of scientific excellence: sex matters.

PMID- 22414803
TI  - Increased Abeta production prompts the onset of glucose intolerance and insulin
      resistance.
AB  - Type 2 diabetes (T2D) mellitus and Alzheimer's disease (AD) are two prevalent
      diseases with comparable pathophysiological features and genetic predisposition.
      Patients with AD are more susceptible to develop T2D. However, the molecular
      mechanism linking AD and T2D remains elusive. In this study, we have generated a
      new mouse model to test the hypothesis that AD would prompt the onset of T2D in
      mice. To test our hypothesis, we crossed Alzheimer APPswe/PS1dE9 (APP/PS1)
      transgenic mice with mice partially deficient in leptin signaling (db/+). Body
      weight, plasma glucose, and insulin levels were monitored. Phenotypic
      characterization of glucose metabolism was performed using glucose and insulin
      tolerance tests. beta-Cell mass, islet volume, and islet number were analyzed by
      histomorphometry. APP/PS1 coexpression in mice with intact leptin receptor
      signaling did not show any metabolic perturbations in glucose metabolism or
      insulin sensitivity. In contrast, APP/PS1 coexpression in db/+ mice resulted in
      nonfasting hyperglycemia, hyperinsulinemia, and hypercholesterolemia without
      changes in body weight. Conversely, fasting blood glucose and cholesterol levels
      remained unchanged. Coinciding with altered glucose metabolism, APP/PS1
      coexpression in db/+ mice resulted in glucose intolerance, insulin resistance,
      and impaired insulin signaling. In addition, histomorphometric analysis of
      pancreata revealed augmented beta-cell mass. Taken together, these findings
      provide experimental evidence to support the notion that aberrant Abeta
      production might be a mechanistic link underlying the pathology of insulin
      resistance and T2D in AD.

PMID- 22414805
TI  - The role of estrogen receptor-alpha and its activation function-1 for growth
      plate closure in female mice.
AB  - High estradiol levels in late puberty induce growth plate closure and thereby
      cessation of growth in humans. In mice, the growth plates do not fuse after
      sexual maturation, but old mice display reduced longitudinal bone growth and high
      dose estradiol treatment induces growth plate closure. Estrogen receptor (ER)
      alpha stimulates gene transcription via two activation functions (AFs), AF-1 and
      AF-2. To evaluate the role of ERalpha and its AF-1 for age-dependent reduction in
      longitudinal bone growth and growth plate closure, female mice with inactivation
      of ERalpha (ERalpha(-/-)) or ERalphaAF-1 (ERalphaAF-1(0)) were evaluated. Old (16
      to 19-mo-old) female ERalpha(-/-) mice showed continued substantial longitudinal
      bone growth, resulting in longer bones (tibia: +8.3%, P < 0.01) associated with
      increased growth plate height (+18%, P < 0.05) compared with wild-type (WT) mice.
      In contrast, the longitudinal bone growth ceased in old ERalphaAF-1(0) mice
      (tibia: -4.9%, P < 0.01). Importantly, the proximal tibial growth plates were
      closed in all old ERalphaAF-1(0) mice while they were open in all WT mice. Growth
      plate closure was associated with a significantly altered balance between
      chondrocyte proliferation and apoptosis in the growth plate. In conclusion, old
      female ERalpha(-/-) mice display a prolonged and enhanced longitudinal bone
      growth associated with increased growth plate height, resembling the growth
      phenotype of patients with inactivating mutations in ERalpha or aromatase. In
      contrast, ERalphaAF-1 deletion results in a hyperactive ERalpha, altering the
      chondrocyte proliferation/apoptosis balance, leading to growth plate closure.
      This suggests that growth plate closure is induced by functions of ERalpha that
      do not require AF-1 and that ERalphaAF-1 opposes growth plate closure.

PMID- 22414806
TI  - Disruption of parathyroid hormone and parathyroid hormone-related peptide
      receptor phosphorylation prolongs ERK1/2 MAPK activation and enhances c-fos
      expression.
AB  - Previous studies have demonstrated that parathyroid hormone (PTH) binding to the
      PTH/PTH-related peptide receptor (PPR) stimulates G protein coupling, receptor
      phosphorylation, beta-arrestin translocation, and internalization of the
      ligand/receptor complex. The extracellular signal-regulated mitogen-activated
      protein kinases 1/2 (ERK1/2 MAPK) are downstream effectors of PPR. In the current
      study, we investigated the role of PPR phosphorylation in the PTH regulation of
      the ERK1/2 MAPK pathway. Short treatment with PTH (0-40 min) of LLCP-K(1) cells
      stably expressing a wild-type (WT) or a phosphorylation-deficient (PD) PPR (WT
      PPR or PD-PPR cells, respectively) results in similar activation of ERK1/2.
      Interestingly, PTH stimulation of ERK1/2 in the WT-PPR cells then decreases as a
      result of longer PTH (60 min) treatment, and inhibition of ERK1/2 by PTH is
      observed at 90 min. Strikingly, the PD-PPR cells exhibit prolonged ERK1/2
      activation up to 90 min of PTH treatment. An ERK1/2-dependent increase in c-fos
      expression is observed in the PD-PPR cells. Subsequently, c-fos expression in the
      WT-PPR and PD-PPR cells was markedly attenuated by a specific ERK1/2 pathway
      inhibitor. Further investigations revealed that PTH treatment causes a robust
      recruitment of a green fluorescent protein-tagged beta-arrestin2 (beta-arrestin2
      GFP) in the WT-PPR cells. In contrast, beta-arrestin2 recruitment was reduced in
      the PD-PPR cells. Importantly, expression of a receptor phosphorylation
      independent beta-arrestin2 (R169E) in the PD-PPR cells restored the biphasic
      effect of PTH on ERK1/2 as in the WT-PPR cells. The study reports a novel role
      for receptor phosphorylation and beta-arrestin2 in the subsequent inhibition of
      the ERK1/2 pathway and in control of gene expression.

PMID- 22414807
TI  - Glucose-mediated control of ghrelin release from primary cultures of gastric
      mucosal cells.
AB  - The peptide hormone ghrelin is released from a distinct group of gastrointestinal
      cells in response to caloric restriction, whereas its levels fall after eating.
      The mechanisms by which ghrelin secretion is regulated remain largely unknown.
      Here, we have used primary cultures of mouse gastric mucosal cells to investigate
      ghrelin secretion, with an emphasis on the role of glucose. Ghrelin secretion
      from these cells upon exposure to different d-glucose concentrations, the glucose
      antimetabolite 2-deoxy-d-glucose, and other potential secretagogues was assessed.
      The expression profile of proteins involved in glucose transport, metabolism, and
      utilization within highly enriched pools of mouse ghrelin cells and within
      cultured ghrelinoma cells was also determined. Ghrelin release negatively
      correlated with d-glucose concentration. Insulin blocked ghrelin release, but
      only in a low d-glucose environment. 2-Deoxy-d-glucose prevented the inhibitory
      effect of high d-glucose exposure on ghrelin release. mRNAs encoding several
      facilitative glucose transporters, hexokinases, the ATP-sensitive potassium
      channel subunit Kir6.2, and sulfonylurea type 1 receptor were expressed highly
      within ghrelin cells, although neither tolbutamide nor diazoxide exerted direct
      effects on ghrelin secretion. These findings suggest that direct exposure of
      ghrelin cells to low ambient d-glucose stimulates ghrelin release, whereas high d
      glucose and glucose metabolism within ghrelin cells block ghrelin release. Also,
      low d-glucose sensitizes ghrelin cells to insulin. Various glucose transporters,
      channels, and enzymes that mediate glucose responsiveness in other cell types may
      contribute to the ghrelin cell machinery involved in regulating ghrelin secretion
      under these different glucose environments, although their exact roles in ghrelin
      release remain uncertain.

PMID- 22414808
TI  - Intracellular and plasma membrane-initiated pathways involved in the [Ca2+]i
      elevations induced by iodothyronines (T3 and T2) in pituitary GH3 cells.
AB  - The role of 3,5,3'-triiodo-l-thyronine (T3) and its metabolite 3,5-diiodo-l
      thyronine (T2) in modulating the intracellular Ca(2+) concentration ([Ca(2+)](i))
      and endogenous nitric oxide (NO) synthesis was evaluated in pituitary GH(3) cells
      in the absence or presence of extracellular Ca(2+). When applied in Ca(2+)-free
      solution, T2 and T3 increased [Ca(2+)](i), in a dose-dependent way, and NO
      levels. Inhibition of neuronal NO synthase by N(G)-nitro-l-arginine methyl ester
      and l-n(5)-(1-iminoethyl)ornithine hydrochloride significantly reduced the
      [Ca(2+)](i) increase induced by T2 and T3. However, while depletion of inositol
      trisphosphate-dependent Ca(2+) stores did not interfere with the T2- and T3
      induced [Ca(2+)](i) increases, the inhibition of phosphatidylinositol 3-kinase by
      LY-294002 and the dominant negative form of Akt mutated at the ATP binding site
      prevented these effects. Furthermore, the mitochondrial protonophore carbonyl
      cyanide 4-(trifluoromethoxy)phenylhydrazone prevented the increases in both
      [Ca(2+)](i) and NO elicited by T2 or T3. Interestingly, rotenone blocked the
      early [Ca(2+)](i) increases elicited by T2 and T3, while antimycin prevented only
      that elicited by T3. Inhibition of mitochondrial Na(+)/Ca(2+) exchanger by
      CGP37157 significantly reduced the [Ca(2+)](i) increases induced by T2 and T3. In
      the presence of extracellular calcium (1.2 mM), under carbonyl cyanide 4
      (trifluoromethoxy)phenylhydrazone, T2 and T3 increased both [Ca(2+)](i) and
      intracellular Na(+) concentration; nimodipine reduced the [Ca(2+)](i) increases
      elicited by T2 and T3, but inhibition of NO synthase and blockade of the
      Na(+)/H(+) pump by 5-(N-ethyl-N-isopropyl)amiloride prevented only that elicited
      by T3; and CB-DMB, bisindolylmaleimide, and LY-294002 (inhibitors of the
      Na(+)/Ca(2+) exchanger, PKC, and phosphatidylinositol 3-kinase, respectively)
      failed to modify the T2- and T3-induced effects. Collectively, the present
      results suggest that T2 and T3 exert short-term nongenomic effects on
      intracellular calcium and NO by modulating plasma membrane and mitochondrial
      pathways that differ between these iodothyronines.

PMID- 22414809
TI  - Extrahepatic tissues compensate for loss of hepatic taurine synthesis in mice
      with liver-specific knockout of cysteine dioxygenase.
AB  - Because hepatic cysteine dioxygenase (CDO) appears to play the major role in
      controlling cysteine catabolism in the intact rat, we characterized the effect of
      a lack of hepatic CDO on the regulation of cysteine and its metabolites at the
      whole body level. In mice with liver-specific deletion of CDO expression, hepatic
      and plasma cysteine levels increased. In addition, in mice with liver-specific
      deletion of CDO expression, the abundance of CDO and the proportion of CDO
      existing as the mature, more active isoform increased in extrahepatic tissues
      that express CDO (kidney, brown fat, and gonadal fat). CDO abundance was also
      increased in the pancreas, where most of the enzyme in both control and liver CDO
      knockout mice was in the more active isoform. This upregulation of CDO
      concentration and active-site cofactor formation were not associated with an
      increase in CDO mRNA and thus presumably were due to a decrease in CDO
      degradation and an increase in CDO cofactor formation in association with
      increased exposure of extrahepatic tissues to cysteine in mice lacking hepatic
      CDO. Extrahepatic tissues of liver CDO-knockout mice also had higher levels of
      hypotaurine, consistent with increased metabolism of cysteine by the
      CDO/cysteinesulfinate decarboxylase pathway. The hepatic CDO-knockout mice were
      able to maintain normal levels of glutathione, taurine, and sulfate. The
      maintenance of taurine concentrations in liver as well as in extrahepatic tissues
      is particularly notable, since mice were fed a taurine-free diet and liver is
      normally considered the major site of taurine biosynthesis. This redundant
      capacity for regulation of cysteine concentrations and production of
      hypotaurine/taurine is additional support for the body's robust mechanisms for
      control of body cysteine levels and indicates that extrahepatic tissues are able
      to compensate for a lack of hepatic capacity for cysteine catabolism.

PMID- 22414810
TI  - Amnesia induced by morphine in spatial memory retrieval inhibited in morphine
      sensitized rats.
AB  - The present study investigated the effect of morphine sensitization on the
      impairment of spatial memory retrieval induced by acute morphine in adult male
      rats. Spatial memory was assessed by 2-day Morris water maze task which included
      training and test day. On the training day, rats were trained by a single
      training session of 8 trials. On the test day, a probe trial consisting of 60s
      free swim period without a platform and the visible test were administered.
      Morphine sensitization was induced by subcutaneous (s.c.) injection of morphine,
      once daily for 3 days followed by 5 days without drug treatment before training.
      The results indicated that acute administration of morphine (7.5mg/kg, s.c.)
      before testing impaired spatial memory on the test day. Pre-test morphine-induced
      amnesia decreased in morphine-sensitized (15 and 20mg/kg, s.c.) rats. Improvement
      in spatial memory retrieval in morphine-sensitized rats was inhibited by once
      daily administration of naloxone (1 and 2mg/kg, s.c.) 30 min prior to the
      injection of morphine for three days. The results suggest that morphine
      sensitization reverses the impairment of spatial memory retrieval induced by
      acute morphine and it is implied that mu-opioid receptors may play an important
      role in this effect.

PMID- 22414811
TI  - Pseudolaric acid B induces mitotic catastrophe followed by apoptotic cell death
      in murine fibrosarcoma L929 cells.
AB  - Pseudolaric acid B (PAB) is the primary biologically active compound isolated
      from the root bark of P. kaempferi Gordon. Previous studies have demonstrated
      that PAB arrests cells in G2/M phase in several cancer cell lines without
      significantly perturbing the G2/M transition-associated proteins. CylinB1, a
      marker for mitotic phase arrest, was up-regulated in cells treated with PAB.
      Therefore, we investigated whether PAB affects cell cycle progression at the
      mitotic phase. The mitotic index increased during a 24h treatment with PAB,
      suggesting that PAB arrested cell cycle progression at mitosis. In addition,
      after a prolonged mitotic arrest, the cells underwent mitotic catastrophe. After
      an extended treatment with PAB (longer than 24h), the protein levels of cylinB1
      and cdc2 significantly decreased in both nuclear and cytosolic extracts.
      According to these results, we concluded that mitotic slippage could be due to
      the inactivation of the cylinB1-cdc2 complex resulting from prolonged treatment
      with PAB. The cells undergoing mitotic catastrophe died via apoptosis.

PMID- 22414812
TI  - Effects of proangiotensin-12 infused continuously over 14 days in conscious rats.
AB  - The carboxyl terminal-extended form of angiotensin I, proangotensin-12, was
      recently identified in rat tissues including the small intestine, cardiac
      ventricles, and kidneys. Single administration of proangiotensin-12 exerts
      vasoconstrictor and pressor effects, probably by conversion to angiotensin II;
      however, there are currently no data available about the subacute effects of
      proangiotensin-12. In the present study, we examined the effects of prolonged
      infusion of proangiotensin-12 in conscious rats. Continuous, subcutaneous
      infusion of 240 pmol/kg/min of proangiotensin-12 gradually elevated blood
      pressure over 14 days, as did the same dose of angiotensin II. The pressor
      effects of proangiotensin-12 were abolished by oral administration of losartan,
      an angiotensin II type 1 receptor blocker, or perindopril, an angiotensin
      converting enzyme (ACE) inhibitor. Meanwhile, angiotensin II-induced elevation of
      blood pressure was inhibited by losartan but not by perindopril. Both the plasma
      aldosterone level and heart weight/body weight ratio were increased by the
      prolonged infusion of proangiotensin-12, but these increases were attenuated by
      losartan and perindopril. The present results suggest that proangiotensin-12
      infused continuously over 14 days exerts pressor effects accompanied with the
      elevation of plasma aldosterone and cardiac hypertrophy in an ACE- and
      angiotensin II type 1 receptor-dependent manner.

PMID- 22414813
TI  - Frontal theta cordance predicts 6-month antidepressant response to subcallosal
      cingulate deep brain stimulation for treatment-resistant depression: a pilot
      study.
AB  - Deep brain stimulation (DBS) of subcallosal cingulate white matter (SCC) may be
      an effective approach for treatment-resistant depression (TRD) that otherwise
      fails to respond to more conventional therapies, but DBS is invasive, costly, and
      has potential for adverse effects. Therefore, it is important to identify
      potential biomarkers for predicting antidepressant response before intervention.
      Resting-state EEG was recorded from 12 TRD patients at pre-treatment baseline,
      after 4 weeks SCC DBS, and after 24 weeks SCC DBS. Lower frontal theta cordance
      (FTC) at baseline (and higher FTC after 4 weeks) predicted lower depression
      severity scores after 24 weeks. Greater FTC increases (baseline-4 weeks)
      predicted greater decreases in depression severity scores subsequently (4-24
      weeks) and over the course of the study (baseline-24 weeks). Predictive
      relationships were topographically specific to theta cordance for frontal
      electrodes. Thus, results from this pilot study suggest that baseline FTC and
      changes early in treatment each have utility as biomarkers for predicting 6-month
      clinical response to SCC DBS for TRD.

PMID- 22414814
TI  - Temporally dependent changes in cocaine-induced synaptic plasticity in the
      nucleus accumbens shell are reversed by D1-like dopamine receptor stimulation.
AB  - Dopaminergic and glutamatergic inputs to the nucleus accumbens shell have a
      central role in reward processing. Non-contingent cocaine administration
      generates a number of long-term AMPA receptor-dependent changes in synaptic
      efficacy. However, the synaptic consequences of cocaine self-administration and
      the potential role of dopamine in these processes remain unclear. Here, we
      examined the influence of D1 dopamine receptor (D1DR) activation on excitatory
      synaptic plasticity in the accumbens shell of adult rats following cocaine self
      administration. Our results indicated that during the first 2 days following
      cocaine exposure both pre- and post-synaptic mechanisms contribute to a net
      decrease in AMPA receptor-mediated signaling. This is reflected by decreased
      frequency of miniature EPSCs (mEPSCs) attributable to enhanced cannabinoid
      receptor activity, decreased mEPSC amplitude, and increased paired-pulse ratio of
      evoked EPSCs. In contrast, the only changes observed in the shell 3-4 weeks
      following cocaine self-administration were increased mEPSCs amplitudes and
      AMPA/NMDA ratios. We further found that although these cocaine-induced
      neuroadaptations during early and late abstinence have different synaptic
      expression mechanisms, they were normalized by stimulation of D1DRs. Thus, pre
      exposure to the D1DR agonist, SKF38393, during the initial period of abstinence
      increased excitatory synaptic strength, but reduced excitatory signaling after
      weeks of abstinence. Taken together, these results indicate that the direction of
      changes in excitatory transmission induced by cocaine self-administration
      switches over the first few weeks of abstinence. Moreover, D1DRs gate the
      stability of these cocaine-induced changes at glutamatergic synapses in the
      accumbens shell by utilizing multiple temporally distinct mechanisms, which has
      implications for the treatment of cocaine craving and addiction.

PMID- 22414815
TI  - The SSRI citalopram affects fetal thalamic axon responsiveness to netrin-1 in
      vitro independently of SERT antagonism.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) signaling is thought to modulate nervous
      system development. Genetic and pharmacological studies support the idea that
      altered 5-HT signaling during development can have enduring consequences on brain
      function and behavior. Recently, we discovered that 5-HT can modulate thalamic
      axon guidance in vitro and in vivo. Embryonic thalamic axons transiently express
      the 5-HT transporter (SERT; Slc6a4) and accumulate 5-HT, suggesting that the SERT
      activity of these axons may regulate 5-HT-modulated guidance cues. We tested
      whether pharmacologically blocking SERT using selective 5-HT reuptake inhibitors
      (SSRIs) would impact the action of 5-HT on thalamic axon responses to netrin-1 in
      vitro. Surprisingly, we observed that two high-affinity SSRIs, racemic citalopram
      ((RS)-CIT) and paroxetine, affect the outgrowth of embryonic thalamic axons, but
      differ with respect to their dependence on SERT blockade. Using a recently
      developed 'citalopram insensitive' transgenic mouse line and in vitro
      pharmacology, we show that the effect of (RS)-CIT effect is SERT independent, but
      rather arises from R-CIT activation of the orphan sigma-1 receptor(sigma1,
      Oprs1). Our results reveal a novel sigma1 activity in modulating axon guidance
      and a 5-HT independent action of a widely prescribed SSRI. By extension, (RS)-CIT
      and possibly other structurally similar SSRIs may have other off-target actions
      that can impact neural development and contribute to therapeutic efficacy or side
      effects.

PMID- 22414816
TI  - Decreased cocaine motor sensitization and self-administration in mice
      overexpressing cannabinoid CB2 receptors.
AB  - The potential involvement of the cannabinoid CB2 receptors (CB2r) in the adaptive
      responses induced by cocaine was studied in transgenic mice overexpressing the
      CB2r (CB2xP) and in wild-type (WT) littermates. For this purpose, the acute and
      sensitized locomotor responses to cocaine, conditioned place preference, and
      cocaine intravenous self-administration were evaluated. In addition, we assessed
      whether CB2r were localized in neurons and/or astrocytes, and whether they
      colocalized with dopamine D1 and D2 receptors (D1Dr and D2Dr). Dopamine (DA)
      extracellular levels in the nucleus accumbens (NAcc), and gene expression of
      tyrosine hydroxylase (TH) and DA transporter (DAT) in the ventral tegmental area
      (VTA), and MU-opioid and cannabinoid CB1 receptors in the NAcc were also studied
      in both genotypes. CB2xP mice showed decreased motor response to acute
      administration of cocaine (10-20 mg/kg) and cocaine-induced motor sensitization
      compared with WT mice. CB2xP mice presented cocaine-induced conditioned place
      aversion and self-administered less cocaine than WT mice. CB2r were found in
      neurons and astrocytes and colocalized with D2Dr in the VTA and NAcc. No
      significant differences in extracellular DA levels in the NAcc were observed
      between genotypes after cocaine administration. Under baseline conditions, TH and
      DAT gene expression was higher and MU-opioid receptor gene expression was lower
      in CB2xP than in WT mice. However, both genotypes showed similar changes in TH
      and MU-opioid receptor gene expression after cocaine challenge independently of
      the pretreatment received. Importantly, the cocaine challenge decreased DAT gene
      expression to a lesser extent in cocaine-pretreated CB2xP than in cocaine
      pretreated WT mice. These results revealed that CB2r are involved in cocaine
      motor responses and cocaine self-administration, suggesting that this receptor
      could represent a promising target to develop novel treatments for cocaine
      addiction.

PMID- 22414817
TI  - Palmitoylethanolamide protects against the amyloid-beta25-35-induced learning and
      memory impairment in mice, an experimental model of Alzheimer disease.
AB  - Alzheimer disease (AD) is the most common form of neurodegenerative dementia.
      Amyloid-beta deposition, neurofibrillary tangle formation, and neuro-inflammation
      are the major pathogenic mechanisms that in concert lead to memory dysfunction
      and decline of cognition. Palmitoylethanolamide (PEA) is the naturally occurring
      lipid amide between palmitic acid and ethanolamine. Despite its clear role in
      inflammation and pain control, only limited in vitro evidence exist about a role
      for PEA in neurodegenerative diseases. Here we describe the neuroprotective
      activities of PEA in mice injected intracerebroventricularly with amyloid-beta 25
      35 (Ab25-35) peptide (9 nmol). We used spatial and non-spatial memory tasks to
      evaluate learning and memory dysfunctions. Ab25-35 injection significantly
      impaired spontaneous alternation performances, water maze spatial reference and
      working-like memory, and novel object recognition test. PEA was administered once
      a day (3-30 mg/kg, subcutaneously), starting 3 h after Ab25-35, for 1 or 2 weeks.
      PEA reduced (10 mg/kg) or prevented (30 mg/kg) behavioral impairments induced by
      Ab25-35 injection. PEA failed to rescue memory deficits induced by Ab25-35
      injection in peroxisome proliferator-activated receptor-alpha (PPAR-alpha) null
      mice. GW7647 (2-(4-(2-(1-cyclohexanebutyl)-3-cyclohexylureido)ethyl)phenylthio)-2
      methylpropionic acid; 5 mg/kg per day), a synthetic PPAR-alpha agonist, mimicked
      the effect of PEA. Acute treatment with PEA was ineffective. According with the
      neuroprotective profile of PEA observed during behavioral studies, experimental
      molecular and biochemical markers induced by Ab25-35 injection, such as lipid
      peroxidation, protein nytrosylation, inducible nitric oxide synthase induction,
      and caspase3 activation, were reduced by PEA treatment. These data disclose novel
      findings about the therapeutic potential of PEA, unrevealing a previously unknown
      therapeutic possibility to treat memory deficits associated with AD.

PMID- 22414818
TI  - Dissociation of hedonic reaction to reward and incentive motivation in an animal
      model of the negative symptoms of schizophrenia.
AB  - We previously showed that mice that selectively and reversibly overexpress
      striatal D2 receptors (D2R-OE) model the negative symptoms of schizophrenia.
      Specifically, D2R-OE mice display a deficit in incentive motivation. The present
      studies investigated the basis for this deficit. First, we assessed whether
      hedonic reaction to reward is intact in D2R-OE mice. We assessed licking behavior
      and video-scored positive hedonic facial reactions to increasing concentrations
      of sucrose in control and D2R-OE mice. We found no difference between D2R-OE mice
      and controls in hedonic reactions. To further understand the basis of the
      motivational deficit, mice were given a choice between pressing a lever for
      access to a preferred reward (evaporated milk) or consuming a freely available
      less preferred reward (home-cage chow). D2R-OE mice pressed less for the
      preferred milk and consumed more of the freely available less preferred chow,
      indicating that striatal overexpression of postsynaptic D2Rs can alter
      cost/benefit computations, leading to a motivational deficit. This motivational
      impairment was ameliorated when the transgene was turned off and D2R levels were
      normalized. Such a deficit may arise from impaired ability to represent the value
      of future rewards. To test this, we used operant concurrent schedules and found
      reduced sensitivity to the value of future outcomes in D2R-OE mice. These results
      demonstrate for the first time in a transgenic animal model of schizophrenia a
      dissociation between hedonic reaction to reward and incentive motivation, and
      show a striking parallel to the proposed neurobiological and psychological
      mechanisms of impaired incentive motivation in schizophrenia.

PMID- 22414819
TI  - Zinc combined with vitamin A reduces upper respiratory tract infection morbidity
      in a randomised trial in preschool children in Indonesia.
AB  - Zn supplementation has shown inconsistent effects on respiratory morbidity in
      young children in developing countries. Few studies have focused on upper
      respiratory tract infection (URTI), a frequent cause of morbidity in this group,
      and potential benefit from Zn supplementation or factors that influence its
      efficacy. We investigated the effects of Zn supplementation on URTI before and
      after vitamin A supplementation. This randomised double-blinded controlled Zn
      supplementation study was conducted on 826 children aged 2-5 years. Placebo or Zn
      (10 mg/d) was given in syrup daily for 4 months, with 200 000 IU vitamin A (60 mg
      retinol) given to all children at 2 months. Health workers visited children every
      3 d for compliance and morbidity information. We found that 84 % of children
      experienced URTI during the study. Zn supplementation reduced the percentage of
      days with URTI (12 % reduction; P = 0.09), with greater impact following vitamin
      A supplementation (20 % reduction; P = 0.01). Vitamin A supplementation was
      associated with a decreased number but an increased duration of URTI episodes. We
      conclude that Zn combined with vitamin A supplementation significantly reduced
      the percentage of days with URTI in a population of preschool Indonesian children
      with marginal nutritional status. The results suggest that vitamin A status
      modifies the efficacy of Zn supplementation on URTI.

PMID- 22414820
TI  - Reliable fabrication of 3 nm gaps between  nanoelectrodes by electron-beam 
      lithography.
AB  - The reliable fabrication of nanoelectrode pairs with predefined separations in
      the few nanometer range is an essential prerequisite for future nanoelectronic
      devices. Here we demonstrate a fine-tuned electron-beam lithographic (EBL)
      fabrication route which is suitable for defining nanoelectrode pairs with a gap
      size down to 3 +/- 1 nm and with a yield of 55%. This achievement is based on an
      optimized two-layer resist system in combination with an adopted developer
      system, as well as on an elaborated nanoelectrode pattern design taking into
      consideration the EBL inherent proximity effect. Thus, even a structural control
      in the nanometer scale is achieved in the EBL process.

PMID- 22414821
TI  - Preclinical evaluation of ice-free cryopreserved arteries: structural integrity
      and hemocompatibility.
AB  - OBJECTIVE: Arterial allografts are routinely employed for reconstruction of
      infected prosthetic grafts. Usually, banked cryopreserved arteries are used;
      however, existing conventional freezing cryopreservation techniques applied to
      arteries are expensive. In contrast, a new ice-free cryopreservation technique
      results in processing, storage and shipping methods that are technically simpler
      and potentially less costly. The objective of this study was to determine whether
      or not ice-free cryopreservation causes tissue changes that might preclude
      clinical use. METHODS: Conventionally frozen cryopreserved porcine arteries were
      compared with ice-free cryopreserved arteries and untreated fresh controls using
      morphological (light, scanning electron and laser scanning microscopy), viability
      (alamarBlue assay) and hemocompatibility methods (blood cell adhesion,
      thrombin/antithrombin-III-complex, polymorphonuclear neutrophil-elastase, beta
      thromboglobulin and terminal complement complex SC5b-9). RESULTS: No
      statistically significant structural or hemocompatibility differences between ice
      free cryopreserved and frozen tissues were detectable. There were no quantitative
      differences observed for either autofluorescence (elastin) or second harmonic
      generation (collagen) measured by laser scanning microscopy. Cell viability in
      ice-free cryopreserved arteries was significantly reduced compared to fresh and
      frozen tissues (p < 0.05). CONCLUSIONS: The formation of ice in aortic artery
      preservation did not make a difference in histology, structure or
      thrombogenicity, but significantly increased viability compared with a
      preservation method that precludes ice formation. Reduced cell viability should
      not reduce in vivo performance. Therefore, ice-free cryopreservation is a
      potentially safe and cost-effective technique for the cryopreservation of blood
      vessel allografts.

PMID- 22414822
TI  - A prospective randomized trial of different supplementary local anesthetic
      techniques after failure of inferior alveolar nerve block in patients with
      irreversible pulpitis in mandibular teeth.
AB  - OBJECTIVE: The objective of this study was to compare the efficacy of
      supplementary repeat inferior alveolar nerve block with 2% lidocaine and
      epinephrine, buccal infiltration with 4% articaine with epinephrine,
      intraligamentary injection, or intraosseous injection (both with 2% lidocaine
      with epinephrine) after failed inferior alveolar nerve block (IANB) for securing
      pain-free treatment in patients experiencing irreversible pulpitis in mandibular
      permanent teeth. METHODS: This randomized clinical trial included 182 patients
      diagnosed with irreversible pulpitis in mandibular teeth. Patients received 2.0
      mL of 2% lidocaine with 1:80,000 epinephrine as an IANB injection. Patients who
      did not experience pain-free treatment received randomly 1 of 4 supplementary
      techniques, namely repeat lidocaine IANB (rIANB), articaine buccal infiltration
      (ABI), lidocaine intraligamentary injection (PDL), or lidocaine intraosseous
      injection (IO). Successful pulp anesthesia was considered to have occurred when
      no response was obtained to the maximum stimulation (80 reading) of the pulp
      tester, at which time treatment commenced. Treatment was regarded as being
      successfully completed when it was associated with no pain. Data were analyzed by
      chi(2) and Fisher exact tests. RESULTS: Of the 182 patients, 122 achieved
      successful pulpal anesthesia within 10 minutes after initial IANB injection; 82
      experienced pain-free treatment. ABI and IO allowed more successful (pain-free)
      treatment (84% and 68%, respectively) than rIANB or PDL supplementary techniques
      (32% and 48%, respectively); this was statistically significant (P = .001).
      CONCLUSIONS: IANB injection alone does not always allow pain-free treatment for
      mandibular teeth with irreversible pulpitis. Supplementary buccal infiltration
      with 4% articaine with epinephrine and intraosseous injection with 2% lidocaine
      with epinephrine are more likely to allow pain-free treatment than
      intraligamentary and repeat IANB injections with 2% lidocaine with epinephrine
      for patients experiencing irreversible pulpitis in mandibular permanent teeth.

PMID- 22414823
TI  - Antagonistic interactions between sodium hypochlorite, chlorhexidine, EDTA, and
      citric acid.
AB  - INTRODUCTION: Root canal irrigants play a significant role in the elimination of
      microorganisms, tissue dissolution, and the removal of debris and smear layer. No
      single solution is able to fulfill these actions completely; therefore, their
      association is required. The aim of this investigation was to review the
      antagonistic interactions occurring when sodium hypochlorite (NaOCl),
      chlorhexidine (CHX), EDTA, and citric acid (CA) are used together during
      endodontic treatment. METHODS: A search was performed in the electronic database
      Medline (articles published through 2011; English language; and the following
      search terms or combinations: "interaction AND root canal irrigant or endodontic
      irrigant or sodium hypochlorite or chlorhexidine," "sodium hypochlorite AND EDTA
      or ethylenediaminetetraacetic acid or citric acid or chelating agent or
      chlorhexidine," and "chlorhexidine AND EDTA or ethylenediaminetetraacetic acid or
      citric acid or chelating agent") to identify publications that studied unwanted
      chemical interactions between NaOCl, CHX, and EDTA and CA. RESULTS: The search
      identified 1,285 publications; 19 fulfilled the inclusion/exclusion criteria of
      the review. Their research methodology was classified as either in vitro or ex
      vivo. CONCLUSIONS: Antagonistic interactions included the loss of free available
      chlorine for NaOCl when in contact with chelators, which consequently reduced the
      tissue dissolution capability and to a lesser extent antimicrobial activities.
      When CHX and NaOCl are mixed, a precipitate forms that can present detrimental
      consequences for endodontic treatment, including a risk of discoloration and
      potential leaching of unidentified chemicals into the periradicular tissues. CHX
      and EDTA mixtures cause a precipitate, whereas CHX and CA do not exhibit
      interaction.

PMID- 22414824
TI  - 10-year survival evaluation for glass-fiber-supported postendodontic restoration:
      a prospective observational clinical study.
AB  - INTRODUCTION: Glass-fiber-reinforced endodontic posts (GFRPs), in combination
      with composite resin core materials, are commonly used to build up damaged
      endodontically treated teeth. However, long-term clinical data are scarce. Thus,
      the aim of this investigation was to evaluate the survival of 3 different GFRP
      systems, taking into account several other relevant factors. METHODS: One-hundred
      forty-nine GFRPs in 122 patients were followed for up to 120 months. GFRPs were
      adhesively luted using the etch-and-rinse technique. The core was built with a
      chemically curing composite resin and restored according to the specific
      prosthetic treatment plan. Cox proportional hazards models were used to evaluate
      the association between clinical variables and the time until failure. RESULTS:
      Within 10 years, 55 failures could be observed (annual failure rate = 4.6%) with
      the most frequent ones being post fracture, loss of post retention (both n = 17),
      endodontic problems (n = 7), and those resulting in tooth extraction (n = 10).
      Sixty posts could be followed up for 105 to 120 months (34 posts lost to follow
      up, [mean (standard deviation) survival time: 74 (43) months]). In crude
      analyses, only the tooth type in favor of posterior teeth compared with anterior
      teeth and the number of remaining cavity walls (in favor of >= 1 compared with no
      wall) were significantly associated with the failure rate. Cox regression
      analysis revealed a significant hazard ratio of 2.0 (95% confidence interval, 1.1
      3.5; P = .021) for tooth type in favor of posterior teeth. CONCLUSIONS: The
      relatively high annual failure rate of GFRPs highlights that the treatment
      decision should take into account the most relevant factors as tooth type and the
      number of remaining cavity walls.

PMID- 22414825
TI  - Comparative analysis of accessory mesial canal identification in mandibular first
      molars by using four different diagnostic methods.
AB  - INTRODUCTION: The objective of the present in vitro study was to compare 4
      diagnostic methods to identify accessory mesial canals (AMCs) in lower first
      molars. METHODS: Forty-four lower first molars were selected for assessment with
      cone-beam computed tomography (CBCT), digital radiography (DR), clinical
      inspection (CI), and dental operating microscope (DOM). Initially, axial images
      were obtained by using CBCT, and radiographs were taken in ortho, mesial, and
      distal angulations. The images were assessed by 2 independent groups of
      examiners, and all of the results obtained remained undisclosed until the end of
      the experiment. Subsequently, root canal access was prepared, and the mesial
      subpulpal groove was located by using sharp endodontic explorers. The roots were
      examined with DOM, and all identified canals were negotiated and instrumented by
      using a ProTaper Rotary System. The results were tabulated and statistically
      analyzed by nonparametric McNemar tests. RESULTS: Twelve AMCs (27.0%) were
      identified by CBCT, and 58.0% were instrumented. No AMCs were visualized in any
      DR examined. Fifteen potential AMCs (34%) were identified by CI, but only 47.0%
      were confirmed after instrumentation. Thirteen AMCs (30.0%) were identified by
      DOM, and 84.0% could be negotiated and instrumented. CONCLUSIONS: There were
      statistically significant differences between the 4 types of assessments for AMC
      identification. There was good agreement between DOM and CBCT, whereas DR and CI
      were not as precise as either of the other 2 diagnostic methods.

PMID- 22414826
TI  - Success rates for removing or bypassing fractured instruments: a prospective
      clinical study.
AB  - INTRODUCTION: The objective of this study was to evaluate the success rates of
      standardized techniques for removing or bypassing fractured instruments from root
      canals and determine whether visualization of the fractured instrument with the
      aid of an operating microscope has any impact on the success rates. METHODS: In
      this prospective study, attempts were made to visualize 112 fractured instruments
      under a dental operating microscope after creating a straight-line access to the
      fragment. By using ultrasonic tips alone or associated with bypassing, the Ruddle
      technique was attempted to remove the 68 visible instruments. Bypassing was
      performed for the 44 nonvisible fragments. The chi(2) test was performed to
      assess whether any significant difference occurred between the success rates
      observed for the visible and nonvisible fractured instrument groups. RESULTS: The
      overall success rate (removal and bypassing) was 70.5% (n = 79). In the visible
      fragment group, the success rate was 85.3% (n = 58), and in the nonvisible
      fragment group it was 47.7% (n = 21). Success rates were significantly higher
      when the fragment was visible (P = .0009). CONCLUSIONS: The standardized
      techniques used in this study for removing or bypassing fractured instruments
      were effective, and approximately 2 times greater success rate was obtained when
      the fragment was visible inside the root canal compared with when it was
      nonvisible.

PMID- 22414827
TI  - In vivo efficacy of three different endodontic irrigation systems for irrigant
      delivery to working length of mesial canals of mandibular molars.
AB  - INTRODUCTION: Many in vitro studies have debated over the ability of different
      irrigant delivery and/or agitation systems to reach the apical third of curved
      root canals; however, little is known about irrigant penetration in vivo.
      Therefore, the purpose of this study was to compare the efficacy of the
      conventional endodontic irrigation needle, passive ultrasonic irrigation (PUI),
      and a negative pressure system for irrigant delivery to working length (WL) of
      mesial canals of mandibular molars. METHODS: Thirty mesial canals of 30 vital
      mandibular first or second molars were randomly assigned into 3 groups (n = 10):
      (1) Monoject syringe with 27-gauge needle; (2) PUI with IrriSafe tip; and (3)
      EndoVac system. All canals were treated following the same preparation protocol
      to size 35/0.04 by using 5.25% NaOCl as irrigant during preparation procedure.
      Before obturation, canals were irrigated with 1 mL of a radiopaque solution by
      using the assigned irrigation system, and a digital radiograph was taken by using
      a parallel technique. With the aid of image editing software the distance between
      WL and maximum irrigant penetration was measured. RESULTS: Mean distances for
      Monoject, PUI, and EndoVac groups were 1.51 mm, 0.21 mm, and 0.42 mm,
      respectively. Analysis of variance test showed statistically significant
      differences between groups (P < .001). Tukey honestly significant difference test
      showed statistically significant differences between the Monoject group and the
      other 2 groups (P < .001) but no significant differences between PUI and EndoVac
      groups (P = .06). CONCLUSIONS: PUI and EndoVac are more effective than the
      conventional endodontic needle in delivering irrigant to WL of root canals.

PMID- 22414828
TI  - Apical periodontium response to enamel matrix derivative as an intracanal
      medication in rat immature teeth with pulp necrosis: radiographic and histologic
      findings.
AB  - INTRODUCTION: The aim of this study was to evaluate the enamel matrix derivative
      (EMD) biomaterial in nonvital immature teeth. METHODS: To arrest root
      development, pulpectomies were performed in the lower first molars of 36 4-week
      old rats; the cavities were left exposed to the oral environment for 3 weeks.
      Then, chemical disinfection was performed, and triple antibiotic paste (TAP) or
      EMD was applied in the root canals. A control group did not receive any
      treatment. Radiographic and histological data were evaluated after 3 and 6 weeks.
      RESULTS: At 3 weeks, TAP promoted a milder inflammatory response and increased
      root lengths compared with the control group. At 6 weeks, root development and
      reduced periapical lesions could be observed in both test groups, mainly because
      of the deposition of a cementum-like tissue. EMD promoted narrower canals
      compared with TAP (P < .05). CONCLUSIONS: EMD deserves attention as a potential
      tool in the treatment of nonvital immature teeth. The ingrowth of cementum-like
      tissues into canal spaces favored dental wall thickness and may contribute to
      tooth resistance and support.

PMID- 22414829
TI  - Coculture of dental pulp stem cells with endothelial cells enhances osteo
      /odontogenic and angiogenic potential in vitro.
AB  - INTRODUCTION: Dental pulp stem cells (DPSCs) have received much attention as a
      promising population of stem cells in regenerative endodontics. Securing a good
      blood supply during regeneration is a challenging task because of the constricted
      apical canal opening, which allows only a limited blood supply. The aim of this
      study was to investigate any potential synergistic effects of dental pulp stem
      cells and endothelial cells (ECs) on osteo-/odontogenic and angiogenic
      differentiation in vitro. METHODS: Different ratios of DPSCs and ECs were
      cultured in direct contact using optimized medium for coculture. The 70%
      confluent cocultures were incubated in the osteo-/odontogenic differentiation
      medium for up to 3 weeks. Alkaline phosphatase (ALP) activity, the expression
      levels of ALP, bone sialoprotein (BSP), dentin sialophosphoprotein (DSPP) genes,
      and alizarin red staining for mineralization at different time points were
      analyzed. The tubular network formation on Matrigel and the gene expression
      levels of CD117, VEGF, CD34, and Flk-1 were used as assays to analyze
      angiogenesis. RESULTS: The quantification of ALP in DPSC:EC cocultures revealed a
      greater ALP activity compared with DPSC-alone cultures. At all the time points,
      1:1 cultures showed a significantly greater ALP activity than that of DPSC-alone
      cultures. Alizarin red staining and quantification revealed a much greater amount
      of calcification in the 1:1 and 1:5 cocultures compared with other cultures (P <
      .01). The expression levels of ALP, BSP, and DSPP genes further confirmed the
      greater osteo-/odontogenic differentiation in cocultures compared with those of
      DPSC-alone cultures. Matrigel assay showed that the addition of DPSCs stabilized
      preexisting vessel-like structures formed by ECs and increased the longevity of
      them. CONCLUSIONS: Direct coculture of DPSCs and ECs enhances the in vitro
      differentiation toward osteo-/odontogenic and angiogenic phenotypes.

PMID- 22414830
TI  - Lipopolysaccharide enhances decorin expression through the Toll-like receptor 4,
      myeloid differentiating factor 88, nuclear factor-kappa B, and mitogen-activated
      protein kinase pathways in odontoblast cells.
AB  - INTRODUCTION: Lipopolysaccharide (LPS) has been shown to regulate the function of
      odontoblasts. However, the molecular mechanisms of the effect of LPS on
      odontoblasts are poorly understood. Decorin (DCN), one of the major matrix
      proteoglycans, is known to affect the mineralization of teeth. In this study, we
      investigated whether LPS can regulate the expression of DCN in odontoblasts and
      determined the intracellular signaling pathways triggered by LPS. METHODS: The
      DCN messenger RNA and protein expression changes in mouse odontoblast-lineage
      cells (OLCs) were detected by real-time polymerase chain reaction (PCR) analysis
      and enzyme-linked immunosorbent assay (ELISA). Whether TLR4, myeloid
      differentiating factor 88 (MyD88), nuclear factor-kappa B (NF-kappaB), or mitogen
      activated protein kinase (MAPK) pathways were involved in the LPS-induced DCN
      expression was determined by examined real-time PCR, ELISA, and luciferase
      activity assay. The activation of extracellular signal-regulated kinase (ERK),
      p38, and JNK in OLCs was measured by Western blot analysis. RESULTS: We found
      that the mouse OLCs expressed DCN. DCN messenger RNA was rapidly induced by LPS
      in a time- and dose-dependent manner. Pretreatment with a MyD88 inhibitory
      peptide, a TLR4 antibody, or a specific inhibitor for NF-kappaB or I Kappa B
      alpha (IkappaBalpha) significantly inhibited LPS-induced DCN expression.
      Moreover, the LPS-mediated increase in kappaB-luciferase activity in OLCs was
      suppressed by the overexpression of dominant negative mutants of TLR4, MyD88, and
      IkappaBalpha but not by a dominant negative mutant of TLR2. In addition, LPS
      stimulation activated the ERK, p38, and JNK MAPK pathways. The pretreatment of
      OLCs with specific inhibitors of the ERK, p38, and JNK MAPK pathways markedly
      offset the LPS-induced up-regulation of DCN expression. CONCLUSIONS: Our results
      show that LPS stimulation can up-regulate the gene expression of DCN via the
      TLR4, MyD88, NF-kappaB, and MAPK pathways in odontoblast cells.

PMID- 22414831
TI  - Vesicular glutamate transporters in axons that innervate the human dental pulp.
AB  - INTRODUCTION: Vesicular glutamate transporters (VGLUTs) are involved in the
      transport of transmitter glutamate into synaptic vesicles and are used as markers
      for glutamatergic neurons. METHODS: To assess which types of VGLUTs are involved
      in the glutamate signaling in pulpal axons and to investigate their distribution,
      we performed light microscopic immunohistochemistry by using antibodies against
      VGLUT1, VGLUT2, calcitonin gene-related peptide, and Western blot analysis in
      human dental pulp. RESULTS: VGLUT1 was expressed in a large number of pulpal
      axons, especially in the peripheral pulp where the axons branch extensively. The
      VGLUT1 immunopositive axons showed bead-like appearance, and the majority of
      these also expressed calcitonin gene-related peptide. VGLUT2 was expressed in few
      axons throughout the pulp. CONCLUSIONS: Our findings suggest that VGLUT1 is
      involved mainly in the glutamate-mediated signaling of pain, primarily at the
      level of the peripheral pulp.

PMID- 22414832
TI  - High-purity hepatic lineage differentiated from dental pulp stem cells in serum
      free medium.
AB  - INTRODUCTION: We have previously differentiated hepatocyte like cells from
      deciduous tooth pulp stem and extracted third molar pulp stem cells with a
      protocol that used fetal bovine serum, but it showed high contaminations of
      nondifferentiated cells. Both the lower purity of hepatically differentiated
      cells and usage of serum are obstacles for application of cell therapy or
      regenerative medicine. Objective of this study was to investigate the capacity
      for and purity of hepatocyte-like differentiation of CD117-positive dental pulp
      stem cells without serum. METHODS: Mesenchymal cells from human deciduous and
      extracted third molar pulp were isolated and expanded in vitro. We separated
      CD117-positive cells by using a magnetic-activated cell sorter. The cells were
      characterized immunofluorescently by using known stem cell markers. For hepatic
      differentiation, the media were supplemented with hepatic growth factor, insulin
      transferrin-selenium-x, dexamethasone, and oncostatin M. Expression of hepatic
      markers alpha fetoprotein, albumin, hepatic nuclear factor-4 alpha, insulin-like
      growth factor-1, and carbamoyl phosphate synthetase was examined
      immunofluorescently after differentiation. The amount of differentiated cells was
      assessed by using flow cytometry. Glycogen storage and urea concentration in the
      medium were defined. RESULTS: Both cell cultures demonstrated a number of cells
      positive for all tested hepatic markers after differentiation, ie, albumin
      positive cells were almost 90% of differentiated deciduous pulp cells. The
      concentration of urea in the media increased significantly after differentiation.
      Significant amount of cytoplasmic glycogen storage was found in the cells.
      CONCLUSIONS: Without serum both cell types differentiated into high-purity
      hepatocyte-like cells. These cells offer a source for hepatocyte lineage
      differentiation for transplantation in the future.

PMID- 22414833
TI  - T-lymphocyte and cytokine expression in human inflammatory periapical lesions.
AB  - INTRODUCTION: Lymphocytes, among many cells, express different sets of cytokines,
      chemokines, and receptors, which are considered important mediators of periapical
      immune response to infection. METHODS: The aim of this study was to evaluate the
      mRNA expression of CD4(+)CD28(+) and CD8(+) T genes and the gene expression of
      interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-17A, IL
      10, CCL2/MCP-1, CCL4, CCL5, CXCR4, CCR5, and receptor activator for nuclear
      factor kappa B ligand (RANKL) in periapical interstitial fluid from human root
      canal infections. The samples were collected immediately after root canal
      cleaning and 7 days later (restrained root canal bacterial load) to characterize
      those gene expressions. RESULTS: Real-time polymerase chain reaction demonstrated
      significantly higher levels of CD4(+)CD28(+) and CD8(+) T-cell markers in the
      former root canal condition and an increase of IL-10 and CXCR4, followed by a
      decrease of proinflammatory cytokines such as RANKL, interferon-gamma, IL-1beta,
      and CCL5. CONCLUSIONS: Analyses of T-lymphocyte and cytokine expression in
      periapical area were able to show that distinct root canal conditions might play
      regulatory roles in controlling local immune/inflammatory processes.

PMID- 22414834
TI  - A comparison of the cytotoxicity and proinflammatory cytokine production of
      EndoSequence root repair material and ProRoot mineral trioxide aggregate in human
      osteoblast cell culture using reverse-transcriptase polymerase chain reaction.
AB  - INTRODUCTION: The purpose of this study was to compare the cytotoxicity and
      cytokine expression profiles of EndoSequence Root Repair Material (ERRM;
      Brasseler, Savannah, GA) putty, ERRM flowable, and ProRoot mineral trioxide
      aggregate (MTA; Dentsply Tulsa Dental, Johnson City, TN) using osteoblast cells
      (MG-63). METHODS: Four millimeters in diameter of each material was placed in the
      center of a 6-well culture plate, and a 2-mL suspension (10(5) cells/mL) of human
      osteoblasts was seeded in each well. Photomicrograph images were used to evaluate
      cytotoxicity as evidenced by the lack of osteoblast cell growth in relation to
      the materials with AH-26 (Dentsply Tulsa Dental) as the positive control. In
      addition, reverse-transcriptase polymerase chain reaction (RT-PCR) was used to
      evaluate the expression of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis
      factor-alpha (TNF-alpha). Cytokine expression of MG-63 cells upon
      lipopolysaccharide treatment was used as controls. RT-PCR results were normalized
      by the expression of the housekeeping gene beta-actin and were used to measure
      cytokine expression. Statistical analysis was performed using analysis of
      variance. RESULTS: Results showed that ERRM putty and MTA exhibited minimal
      levels of cytotoxicity; however, ERRM was slightly more cytotoxic although not
      statistically significant. The expression of IL-1beta, IL-6, and IL-8 was
      detected in all samples with minimal TNF-alpha expression. CONCLUSIONS: We
      concluded that ERRM and MTA showed similar cytotoxicity and cytokine expressions.

PMID- 22414835
TI  - In vitro evaluation of MTAD and nisin in combination against common pathogens
      associated with root canal infection.
AB  - INTRODUCTION: Many pathogenic microorganisms were found in an infected root
      canal. The object of this study was to evaluate the effect of MTAD in combination
      with nisin on the pathogens associated with root canal infection. METHODS: The
      survival rates of 9 pathogenic bacteria were determined after 1-, 5-, and 10
      minute treatment with MTAD, MTAN (substitution of doxycycline with nisin), and
      MTADN (nisin in combination with doxycycline). The survival rates of Enterococcus
      faecalis in the starvation phase and pretreatment alkalization as well as in the
      normal physiological state under MTAD, MTAN, and MTADN challenge for 1, 5, and 10
      minutes were evaluated and compared. Furthermore, scanning electron microscopy
      was used to observe the morphologic modification of Actinomyces naeslundii,
      Lactobacillus paracasei, and Porphyromonas gingivalis after MTAD and MTADN
      treatment. RESULTS: L. fermenti, L. paracasei, A. viscosus, A. naeslundii,
      Streptococcus gordonii, and Peptostreptococcus were more sensitive to MTADN and
      MTAN than to MTAD. MTAD, MTAN, and MTADN showed a rapid antibacterial effect on
      P. gingivalis, Prevotella intermedia, and Fusobacterium nucleatum. Enterococcus
      faecalis in the stress state was as sensitive to MTAD, MTAN, and MTADN as the
      control E. faecalis. Furthermore, in the observation of scanning electron
      microscopy, the membranes in A. naeslundii and L. paracasei presented significant
      rupture, and P. gingivalis did not exhibit significant damage after MTADN
      treatment. CONCLUSIONS: MTAD in combination with nisin improved antibacterial
      efficacy against pathogens, especially for some gram-positive bacteria associated
      with persistent intracanal infection. Therefore, the combination had the
      potential to be used as an effective intracanal irrigation.

PMID- 22414836
TI  - Cytotoxicity and genotoxicity of root canal sealers based on mineral trioxide
      aggregate.
AB  - INTRODUCTION: MTA has good biological properties, and it is a mineralization
      inducing material with different indications in endodontics. Initially this
      material was not recommended as root canal sealer. However, a resin sealer based
      on mineral trioxide aggregate (MTA Fillapex) was recently released with this
      indication. Because MTA is in contact with the periodontal tissues, bone, and
      pulp, it is important to know its cytotoxic and genotoxic effects. The purpose of
      this study was to evaluate the cytotoxicity and genotoxicity of MTA canal sealer
      (Fillapex) compared with white MTA cement and AH Plus. METHODS: Chinese hamster
      fibroblasts (V79) were placed in contact with different dilutions of culture
      media previously exposed to such materials. Cytotoxicity was evaluated by methol
      thiazol-diphenyl tetrazolium assay in spectrophotometer to check the viability
      rate and cell survival. The genotoxicity was accessed by the micronucleus
      formation assay. Cell survival rate and micronuclei number were assessed before
      and after exposure to cement extracts, and the results were statistically
      analyzed by Kruskal-Wallis and Dunn tests (P < .05). RESULTS: The results showed
      that the cell viability remained above 50% in white MTA group for all dilutions.
      AH Plus induced an intermediate cytotoxicity in a dilution-dependent manner,
      followed by Fillapex MTA. CONCLUSIONS: White MTA group was the less cytotoxic
      material in this study. Both AH Plus and Fillapex MTA sealer showed the lowest
      cell viability rates and caused an increased micronucleus formation when compared
      with control untreated group.

PMID- 22414837
TI  - Effects of various mixing techniques on push-out bond strengths of white mineral
      trioxide aggregate.
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of 3 different
      mixing methods on push-out bond strength of white tooth-colored mineral trioxide
      aggregate (MTA). METHODS: Sixty 2-mm-thick root sections were prepared from 60
      single-rooted human teeth and filled with MTA. The samples were randomly divided
      into 3 groups (n = 20) of MTA mixed by ultrasonic, trituration, or conventional
      methods and then allowed to set for 72 hours in a synthetic tissue fluid
      environment. Push-out bond strength values of the specimens were measured by a
      universal testing machine and examined under a stereomicroscope at * 4 to
      determine the nature of the bond failure. RESULTS: The means of push-out bond
      strength values of white MTA in the ultrasonic, conventional, and trituration
      groups were 105.67 +/- 12.79, 118.95 +/- 12.76, and 99.60 +/- 14.27 MPa,
      respectively. The differences between the 3 groups were not statistically
      significant. CONCLUSIONS: On the basis of the results of this study, it can be
      concluded that different mixing methods have no significant effect on push-out
      bond strength of white MTA.

PMID- 22414838
TI  - Canal shaping with WaveOne Primary reciprocating files and ProTaper system: a
      comparative study.
AB  - INTRODUCTION: This study compared the canal curvature and axis modification after
      instrumentation with WaveOne Primary reciprocating files (Dentsply Maillefer,
      Ballaigues, Switzerland) and nickel-titanium (NiTi) rotary ProTaper (Dentsply
      Maillefer). METHODS: Thirty ISO 15, 0.02 taper, Endo Training Blocks (Dentsply
      Maillefer) were used. In all specimens, the glide path was achieved with PathFile
      1, 2, and 3 (Dentsply Maillefer) at the working length (WL). Specimens were then
      assigned to 1 of 2 groups for shaping: specimens in group 1 were shaped with
      ProTaper S1-S2-F1-F2 at the WL and specimens in group 2 were shaped with WaveOne
      Primary reciprocating files at the WL. Pre- and postinstrumentation digital
      images were superimposed and processed with Matlab r2010b (The MathWorks Inc,
      Natick, MA) software to analyze the curvature-radius ratio (CRr) and the relative
      axis error (rAe), representing canal curvature modification. Data were analyzed
      with one-way balanced analyses of variance at 2 levels (P < .05). RESULTS: The
      instrument factor was extremely significant for both the CRr parameter (F(1) =
      9.59, P = .004) and the rAe parameter (F(1) = 13.55, P = .001). CONCLUSIONS:
      Canal modifications are reduced when the new WaveOne NiTi single-file system is
      used.

PMID- 22414839
TI  - Evaluation of push-out bond strength of two endodontic post systems.
AB  - INTRODUCTION: The aim of this study was to evaluate the push-out bond strengths
      of a new polyfiber post system and a fiber post that were adhesively luted with a
      dual-cure resin cement. METHODS: Forty single-rooted human maxillary teeth were
      sectioned below the cementoenamel junction, and the roots were endodontically
      treated. The roots were randomly divided into 2 groups of 20 specimens each
      according to the post type used: SpiraPost (group A; DMG, Englewood, NJ) and DT
      Light-Post Illusion X-RO (group B; Bisco Inc, Schaumburg, IL). All posts were
      cemented with dual-cure resin cement. Bonded specimens were cut into 1-mm-thick
      sections, and push-out tests were performed using a universal testing machine.
      All specimens were loaded until fracture, and the failure modes were evaluated
      with a stereomicroscope at 50* magnification. Representative specimens were
      analyzed by scanning electron microscopy. RESULTS: Push-out bond strength was
      significantly affected by the type of post (P < .05). In all root sections, the
      SpiraPost push-out bond strength values were significantly higher than that those
      of DT Light-Post Illusion X-RO (P < .05). Cohesive failure within the post was
      the most frequent type of failure for the SpiraPost system. CONCLUSIONS: In all
      root segments, the SpiraPost system provided significantly increased post
      retention compared with the fiber post.

PMID- 22414840
TI  - An in vitro cyclic fatigue analysis of different endodontic nickel-titanium
      rotary instruments.
AB  - INTRODUCTION: The study compared Twisted File (TF) with 3 traditionally
      manufactured systems to determine whether changes in the manufacturing process
      improved the cyclic fatigue resistance. METHODS: Four rotary file systems, (1)
      ProFile (PF), (2) Mtwo, (3) K3, and (4) TF, were tested in artificial canals with
      45 degrees  and 90 degrees  angles of curvature. Ten instruments each of the 4
      file systems were tested in both angles of curvature (n = 10). All instruments
      had identical size and taper (.06/0.25 tip diameter). RESULTS: A statistically
      significant difference (P < .05) was noted between TF and other nickel-titanium
      instruments in both 45 degrees  and 90 degrees  angles of curvature. TF showed
      the greatest mean number of cycles to failure. There was no statistical
      difference between PF and K3 (P > .05) in both canal curvatures; however,
      statistically significant difference (P < .05) was observed between Mtwo and the
      other 2 traditionally manufactured instruments. Mtwo showed the lowest mean
      number of cycles to failure. CONCLUSIONS: Under the conditions of this study,
      size .06/0.25 TF was significantly more resistant to fatigue than the other 3
      instrument systems produced with the traditional grinding process.

PMID- 22414841
TI  - Are endodontically treated incisors reliable abutments for zirconia-based fixed
      partial dentures in the esthetic zone?
AB  - INTRODUCTION: This ex vivo pilot study tested the influence of defect extension
      and quartz-fiber post placement (QFP) on the ex vivo survival rate and fracture
      resistance of root-treated upper central incisors served as abutments for
      zirconia 2-unit cantilever fixed partial dentures (2U-FPDs) exposed to 10 years
      of simulated clinical function. METHODS: Human maxillary central incisors were
      endodontically treated and divided into the following 5 groups (n = 8): (1)
      access cavity filled with core build-up composite, (2) biproximal class III
      cavities filled as in group 1, (3) specimens restored as in group 2 with QFP
      placed, (4) specimens decoronated and core buildup as in group 1, and (5)
      specimens restored as in group 4 but with QFP as in group 3. On all specimens, 2U
      FPDs were placed with dual-curing resin cement. In order to simulate 10 years of
      clinical function, specimens were exposed to thermal cycling and mechanical
      loading with subsequent loading to failure. Kaplan-Meier curves were constructed,
      and log-rank tests were performed. Fracture force and patterns were compared by
      means of Kruskal-Wallis, Mann-Whitney U (post hoc), and Fisher exact tests,
      respectively (P = .05). RESULTS: For specimens only with an access cavity, it was
      observed that 25% had catastrophic tooth fractures and the lowest load-to
      fracture values. In all other groups, chipping combined with or without debonding
      occurred. Groups did not differ significantly regarding the survival rate (P =
      .603) and fracture patterns (P = .633), but they did for fracture load including
      technical failures (P = .017). CONCLUSIONS: After 10 years of simulated clinical
      function, both defect extension and placement of QFP had no significant influence
      on survival of root-treated upper central incisors as abutments restored with
      zirconia-based 2U-FPDs.

PMID- 22414842
TI  - Treatment of root canal biofilms of Enterococcus faecalis with ozone gas and
      passive ultrasound activation.
AB  - INTRODUCTION: Biofilms of resistant species such as Enterococcus faecalis pose a
      major challenge in the treatment of root canals with established periapical
      disease. This study examined the effects of gaseous ozone delivered into saline
      on biofilms of E. faecalis in root canals of extracted teeth with and without the
      use of passive ultrasonic agitation. METHODS: Biofilms of E. faecalis were
      established over 14 days in 70 single roots that had undergone biomechanical
      preparation followed by gamma irradiation. The presence and purity of biofilms
      were confirmed using scanning electron microscopy and culture. Biofilms were
      treated with saline (negative control), 1% sodium hypochlorite for 120 seconds
      (positive control), ozone (140 ppm ozone in air at 2 L/min delivered into saline
      using a cannula for 120 seconds), saline with passive ultrasonic activation (70
      kHz and 200 mW/cm(2) applied to an ISO 15 file held passively within the canal,
      for 120 seconds), and ozone followed immediately by ultrasonic agitation. After
      treatment, samples were taken from the biofilm and serially diluted for plate
      counting. RESULTS: Analysis revealed that 1% sodium hypochlorite was the most
      effective disinfecting agent followed by ozone combined with ultrasonic
      agitation, ozone alone, and finally ultrasonic alone. CONCLUSIONS: Although none
      of the treatment regimes were able to reliably render canals sterile under the
      conditions used, ozone gas delivered into irrigating fluids in the root canal may
      be useful as an adjunct for endodontic disinfection.

PMID- 22414843
TI  - Effect from cyclic fatigue of nickel-titanium rotary files on torsional
      resistance.
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of cyclic fatigue
      on the torsional resistance of nickel-titanium (NiTi) rotary instruments.
      METHODS: ProFile (#25/0.06; Dentsply Maillefer, Ballaigues, Switzerland) and
      ProTaper (F1, Dentsply Maillefer), both of which have the same external diameter
      at D5, were tested using a fatigue testing machine for the mean number of cycles
      of failure (mNCF). Then, new files were cyclic precycled to 4 conditions (ie, 0%,
      25%, 50%, and 75% of the mNCF) before the torsional resistance test was performed
      on these cyclic preloaded files. A uniform clockwise rotation was applied to the
      file in a straight state in a torsion tester. The torsional load and distortion
      angle were recorded during rotation until the file succumbed to the torque. The
      toughness was computed. The results were analyzed statistically using one-way
      analysis of variance and the Duncan post hoc comparison to find any differences
      between groups at a significance level of 95%. RESULTS: In both ProFile and
      ProTaper groups, the 75% preloading groups had significantly lower torsional
      strength than other preloaded files. In the ProFile group, the 50% and 75%
      preloading groups had a smaller distortion angle until fracture than the 25% and
      no preloading groups. The 75% preloading group showed a lower toughness value
      than the 25% and no preloading groups. In the ProTaper group, all preloading
      groups had less distortion and toughness than the no preloading group.
      Fractographic examinations revealed the 75% preloaded files showed less amount of
      reverse-wound flute than other preloading groups. CONCLUSIONS: Within the
      limitations of the methodology, it could be concluded that approximate 75% cyclic
      fatigue may reduce the torsional resistance of NiTi rotary instruments
      significantly.

PMID- 22414844
TI  - Effect of laser-activated irrigation of 1320-nanometer Nd:YAG laser on sealer
      penetration in curved root canals.
AB  - INTRODUCTION: The purpose of this study was to investigate the efficacy of laser
      activated irrigation (LAI) of 1320-nm neodymium-doped:yttrium-aluminum-garnet
      (Nd:YAG) laser on sealer penetration into dentinal tubules in the presence of
      5.25% sodium hypochlorite (NaOCl) or 17% ethylenediaminetetraacetic acid (EDTA).
      METHODS: The curved root canals (>20 degrees ) from 63 extracted human molars
      (negative control, n = 3) were prepared to size #30.06 with NaOCl irrigation.
      Teeth were divided into 4 groups (n = 15) as follows: group N, NaOCl irrigation
      without LAI; group E, EDTA irrigation without LAI; group NL, LAI with NaOCl;
      group EL, LAI with EDTA. In all groups, the laser fiber was inserted and
      withdrawn 4 times for 5 seconds each. Teeth were obturated with gutta-percha and
      fluorescent-labeled sealer. Transverse sections at 2 and 5 mm from root apex were
      examined with confocal laser scanning microscopy, and the percentage of sealer
      penetration into dentinal tubules was measured. RESULTS: Groups E, NL, and EL
      showed higher percentage of sealer penetration than group N (P < .05). With NaOCl
      as irrigant, LAI (group NL) resulted in significantly higher amount of sealer
      penetration than nonactivated group (group N) in both levels (P < .05). However,
      with EDTA, no significant differences in sealer penetration were observed between
      the laser-activated group (group EL) and its nonactivated counterpart (group E)
      in both levels (P > .05). CONCLUSIONS: The 1320-nm Nd:YAG laser activation with
      either NaOCl or EDTA was much better than NaOCl irrigation alone and as effective
      as EDTA final flush for sealer penetration into dentinal tubules. Additional use
      of laser with EDTA did not improve the quality of obturation in the curved
      canals.

PMID- 22414845
TI  - Failure of setting of mineral trioxide aggregate in the presence of fetal bovine
      serum and its prevention.
AB  - INTRODUCTION: The purpose of this study was to examine the effect of fetal bovine
      serum (FBS) on the setting of 2 white mineral trioxide aggregates (MTAs) and to
      determine if calcium chloride (CaCl(2)) alters the setting behavior of both MTAs
      under this condition. METHODS: Two types of MTA cements (ProRoot MTA [Dentsply
      Tulsa Dental, Tulsa, OK] and MTA-Angelus [Angelus Dental Solutions, Londrina,
      Brazil]) were mixed with either distilled water (DW) or 10% CaCl(2) solution.
      Mixed MTA was placed in a polyethylene mold, and each mold was then placed in
      saline or FBS-soaked Oasis. After storing for 4 days, the MTA samples were
      removed from the molds, and the microhardness was independently measured at 3
      different levels: 0.5 mm, 2 mm, and 4 mm away from the bottom in contact with the
      immersion solution. RESULTS: None of the samples mixed with DW and exposed to FBS
      for 4 days had set at the 0.5-mm and 2-mm levels. CaCl(2) was effective in
      reducing (the 0.5-mm level) or eliminating (the 2- and 4-mm levels) the adverse
      effect of FBS. The groups with short-term exposure to FBS had the same surface
      microhardness as the groups stored in saline-soaked Oasis. CONCLUSIONS: MTA did
      not set when the mixed MTA was exposed to FBS for 4 days. In these cases, 10%
      CaCl(2) helped the setting of MTA, and the effect was more pronounced in ProRoot
      MTA than in MTA-Angelus. In contrast, short-term exposure to FBS had minimal or
      no detrimental effects on the setting behaviors of both MTAs.

PMID- 22414846
TI  - Cyclic fatigue and torsional resistance of two new nickel-titanium instruments
      used in reciprocation motion: Reciproc versus WaveOne.
AB  - INTRODUCTION: The use of reciprocating movement was claimed to increase the
      resistance of nickel-titanium (NiTi) file to fatigue in comparison with
      continuous rotation. Recently 2 new brands of NiTi files have been marketed for
      use in a RM mode. The purpose of this study was to compare the cyclic fatigue
      resistance and torsional resistance of these 2 files, Reciproc and WaveOne.
      METHODS: Cyclic fatigue test with a simultaneous pecking motion was performed
      with the instrument (n = 10 each) operating in the recommended reciprocation
      motion until fracture for the Reciproc R25 and WaveOne Primary files. ProTaper F2
      was tested in continuous rotation to serve as a control for comparison. The
      number of cycles to fracture (NCF) was determined by measuring the time to
      fracture. The length of the fragment was measured and the fracture surface was
      examined by using scanning electron microscopy. Torsional strength was measured
      by using a torsiometer after fixing the apical 5 mm of the instrument rigidly.
      Statistical analysis was performed by using one-way analysis of variance.
      RESULTS: The results showed that Reciproc had a higher NCF and WaveOne had a
      higher torsional resistance than the others. Both reciprocating files
      demonstrated significantly higher cyclic fatigue and torsional resistances than
      ProTaper (P < .05). The fractographic analysis showed typical features of cyclic
      fatigue and torsional failure for all instruments. CONCLUSIONS: The 2 brands of
      NiTi file for use with a reciprocation motion seem to have superior mechanical
      properties.

PMID- 22414847
TI  - Evaluation of antibacterial effects by atmospheric pressure nonequilibrium
      plasmas against Enterococcus faecalis biofilms in vitro.
AB  - INTRODUCTION: The aim of this study was to evaluate the in vitro antibacterial
      activity by atmospheric pressure nonequilibrium plasmas (APNPs) as an effective
      approach against bacterial biofilms in root canal systems during endodontic
      therapy. METHODS: Sterile cover slips were placed into the wells of tissue
      culture plates to permit the formation of Enterococcus faecalis biofilms.
      Biofilms were treated for 5 minutes with APNPs or 2% chlorhexidine digluconate
      (CHX). The viability of biofilm bacteria was analyzed by staining and confocal
      laser scanning microscopy. In addition, infected single-rooted teeth were exposed
      to APNPs or 2% CHX for 5, 10, and 15 minutes. After treatment, the root canals
      were flushed, and the resulting suspensions were inoculated onto brain-heart
      infusion agar to assess bacterial survival. Finally, micro-computed tomography
      scanning was used to observe and verify the root canal systems relative to the
      antibacterial effects obtained. RESULTS: Treatment for 5 minutes with APNPs or 2%
      CHX killed the majority of bacteria in the E. faecalis biofilms. Moreover, APNP
      treatment was as effective as 2% CHX for inactivating bacteria in infected root
      canals (P > .05). Bacterial survival after treatment with APNPs or 2% CHX
      remarkably reduced with increasing exposure times (P < .05). There was no
      significant difference between bacterial survival in complex root canal systems
      and simple straight canals (P > .05). CONCLUSIONS: APNPs can be an effective
      adjunct to standard endodontic antimicrobial treatment.

PMID- 22414848
TI  - Surgical management of vertical root fractures for posterior teeth: report of
      four cases.
AB  - INTRODUCTION: The objective of this article was to present a surgical treatment
      option for teeth with incomplete vertical root fracture in maxillary and
      mandibular posterior teeth. METHODS: Four cases are presented in which 1
      endodontically treated maxillary or mandibular molar had an incomplete vertical
      root fracture involving 1 of the roots. The tooth underwent a flap elevation
      procedure to visualize the pattern of bone loss and assess the extent of root
      fracture. The fracture line was eliminated by resecting the root in a beveled
      manner, after which root-end preparation and root-end filling were performed by
      using mineral trioxide aggregate. The osteotomy was covered with an absorbable
      collagen membrane. Cases were followed up for 8-24 months after surgery. RESULTS:
      The procedure was shown to be predictable and successful in this series. Root
      length was preserved, and tooth extraction was avoided. CONCLUSIONS: The
      microsurgical treatment option for multirooted teeth with incomplete vertical
      root fracture resulted in long-term clinical success.

PMID- 22414849
TI  - The effect of Alzheimer's disease and Parkinson's disease on olfaction: a meta
      analysis.
AB  - Impaired sense of smell is one of the earliest clinical features in both
      Alzheimer's disease (AD) and Parkinson's disease (PD). A meta-analysis was
      performed on articles obtained from the PubMed database in order to determine
      what aspects of olfaction are affected in these two diseases. By applying strict
      criteria, we included a total of 81 studies meeting the following criteria: (1)
      patients had a clinical diagnosis of AD or PD; (2) patients were compared to a
      healthy control group; (3) patients and controls were age-matched; (4) olfactory
      function was assessed by means of a psychophysical olfactory test; (5) mean and
      standard deviation were reported. Results indicate that AD and PD patients are
      more impaired on odor identification and recognition tasks than on odor detection
      thresholds task. In addition, PD patients are more impaired on detection
      thresholds than AD patients. These results suggest that PD patients are more
      impaired on low-level perceptual olfactory tasks whereas AD patients are more
      strongly impaired on higher-order olfactory tasks involving specific cognitive
      processes. The effect appears more pronounced for AD than PD, which seem to be
      affected more homogeneously. In conclusion, olfactory identification and
      recognition appear as the most interesting candidates to be included in a battery
      to detect subclinical cases in AD. In parallel, detection thresholds should be
      included in such a battery for subclinical PD patients.

PMID- 22414850
TI  - Oral ibuprofen versus intravenous ibuprofen or intravenous indomethacin for the
      treatment of patent ductus arteriosus in preterm infants: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Pharmacological closure of patent ductus arteriosus (PDA) is commonly
      achieved by intravenous (IV) administration of ibuprofen or indomethacin.
      Occasionally, oral ibuprofen is used for PDA treatment although its efficacy and
      safety are unclear. OBJECTIVES: To systematically review randomized and quasi
      randomized trials comparing oral ibuprofen with IV ibuprofen or IV indomethacin
      for closure of PDA in preterm infants. METHODS: The standard search methods of
      the Cochrane Neonatal Review Group were used. RESULTS: We identified two studies
      (n = 166) of good methodological quality comparing oral ibuprofen with IV
      ibuprofen and three small trials (n = 92) of moderate methodological quality
      comparing oral ibuprofen to IV indomethacin. Meta-analysis showed higher PDA
      closure rate of oral ibuprofen versus IV ibuprofen but no difference between oral
      ibuprofen and IV indomethacin. Meta-analysis did not indicate a significant
      difference in adverse effects. CONCLUSION: Oral ibuprofen for PDA closure appears
      to be as effective as IV ibuprofen and IV indomethacin. Due to small sample size,
      lack of data in extremely preterm neonates, and methodological limitations of
      reviewed trials, definitive conclusions cannot be drawn. Randomized trials with a
      low risk of bias and adequate sample size in extremely preterm infants are
      urgently needed.

PMID- 22414852
TI  - Community-level response of coastal microbial biofilms to ocean acidification in
      a natural carbon dioxide vent ecosystem.
AB  - The impacts of ocean acidification on coastal biofilms are poorly understood.
      Carbon dioxide vent areas provide an opportunity to make predictions about the
      impacts of ocean acidification. We compared biofilms that colonised glass slides
      in areas exposed to ambient and elevated levels of pCO(2) along a coastal pH
      gradient, with biofilms grown at ambient and reduced light levels. Biofilm
      production was highest under ambient light levels, but under both light regimes
      biofilm production was enhanced in seawater with high pCO(2). Uronic acids are a
      component of biofilms and increased significantly with high pCO(2). Bacteria and
      Eukarya denaturing gradient gel electrophoresis profile analysis showed clear
      differences in the structures of ambient and reduced light biofilm communities,
      and biofilms grown at high pCO(2) compared with ambient conditions. This study
      characterises biofilm response to natural seabed CO(2) seeps and provides a
      baseline understanding of how coastal ecosystems may respond to increased pCO(2)
      levels.

PMID- 22414851
TI  - Androgen receptors, sex behavior, and aggression.
AB  - Androgens are intricately involved in reproductive and aggressive behaviors, but
      the role of the androgen receptor in mediating these behaviors is less defined.
      Further, activity of the hypothalamic-pituitary-gonadal axis and hypothalamic
      pituitary-adrenal axis can influence each other at the level of the androgen
      receptor. Knowledge of the mechanisms for androgens' effects on behaviors through
      the androgen receptor will guide future studies in elucidating male reproductive
      and aggressive behavior repertoires.

PMID- 22414853
TI  - Diaminothiazoles inhibit angiogenesis efficiently by suppressing Akt
      phosphorylation.
AB  - The prevention of neovessel formation or angiogenesis is a recent popular
      strategy for limiting and curing cancer. Diaminothiazoles are a class of
      compounds that have been reported to show promise in the treatment of cancer by
      inhibiting cancer cell proliferation and inducing apoptosis, because of their
      effects on microtubules and as inhibitors of cyclin-dependent kinases. Many
      microtubule-targeting agents are being studied for their antiangiogenic activity,
      and a few have shown promising activity in the treatment of cancer. Here, we
      report that diaminothiazoles can be highly effective as antiangiogenic agents, as
      observed in the chick membrane assay. The lead compound, 4-amino-5-benzoyl-2-(4
      methoxyphenylamino)thiazole (DAT1), inhibits endothelial cell processes such as
      invasion, migration, and tubule formation, which require a functional
      cytoskeleton. DAT1 also decreases the expression of cell adhesion markers. The
      antiangiogenic activities of DAT1 occur at concentrations that are not cytotoxic
      to the normal endothelium. Analysis of intracellular signaling pathways shows
      that DAT1 inhibits Akt phosphorylation, which is actively involved in the
      angiogenic process. The antiangiogenic properties of diaminothiazoles, in
      addition to their promising antimitotic and cytotoxic properties in cancer cell
      lines, give them an extra advantage in the treatment of cancer.

PMID- 22414855
TI  - A model-based approach to predicting the human pharmacokinetics of a monoclonal
      antibody exhibiting target-mediated drug disposition.
AB  - In the drug discovery and development setting, the ability to accurately predict
      the human pharmacokinetics (PK) of a candidate compound from preclinical data is
      critical for informing the effective design of the first-in-human trial. PK
      prediction is especially challenging for monoclonal antibodies exhibiting
      nonlinear PK attributed to target-mediated drug disposition (TMDD). Here, we
      present a model-based method for predicting the PK of PF-03446962, an IgG2
      antibody directed against human ALK1 (activin receptor-like kinase 1) receptor.
      Systems parameters as determined experimentally or obtained from the literature,
      such as binding affinity (k(on) and k(off)), internalization of the drug-target
      complex (k(int)), target degradation rate (k(deg)), and target abundance (R(0)),
      were directly integrated into the modeling and prediction. NONMEM 7 was used to
      model monkey PK data and simulate human PK profiles based on the construct of a
      TMDD model using a population-based approach. As validated by actual patient data
      from a phase I study, the human PK of PF-03446962 were predicted within 1- to 2
      fold of observations. Whereas traditional approaches fail, this approach
      successfully predicted the human PK of a monoclonal antibody exhibiting
      nonlinearity because of TMDD.

PMID- 22414854
TI  - Is hydrogen sulfide-induced suspended animation general anesthesia?
AB  - Hydrogen sulfide (H(2)S) depresses mitochondrial function and thereby metabolic
      rates in mice, purportedly resulting in a state of "suspended animation."
      Volatile anesthetics also depress mitochondrial function, an effect that may
      contribute to their anesthetic properties. In this study, we ask whether H(2)S
      has general anesthetic properties, and by extension, whether mitochondrial
      effects underlie the state of anesthesia. We compared loss of righting reflex,
      electroencephalography, and electromyography in mice exposed to metabolically
      equipotent concentrations of halothane, isoflurane, sevoflurane, and H(2)S. We
      also studied combinations of H(2)S and anesthetics to assess additivity. Finally,
      the long-term effects of H(2)S were assessed by using the Morris water maze
      behavioral testing 2 to 3 weeks after exposures. Exposure to H(2)S decreases O(2)
      consumption, CO(2) production, and body temperature similarly to that of the
      general anesthetics, but fails to produce a loss of righting reflex or muscle
      atonia at metabolically equivalent concentrations. When combined, H(2)S
      antagonizes the metabolic effects of isoflurane, but potentiates the isoflurane
      induced loss of righting reflex. We found no effect of prior H(2)S exposure on
      memory or learning. H(2)S (250 ppm), not itself lethal, produced delayed
      lethality when combined with subanesthetic concentrations of isoflurane. H(2)S
      cannot be considered a general anesthetic, despite similar metabolic suppression.
      Metabolic suppression, presumably via mitochondrial actions, is not sufficient to
      account for the hypnotic or immobilizing components of the anesthetic state.
      Combinations of H(2)S and isoflurane can be lethal, suggesting extreme care in
      the combination of these gases in clinical situations.

PMID- 22414856
TI  - Attenuation of cisplatin-induced renal injury by inhibition of soluble epoxide
      hydrolase involves nuclear factor kappaB signaling.
AB  - Acute kidney injury is associated with a significant inflammatory response that
      has been the target of renoprotection strategies. Epoxyeicosatrienoic acids
      (EETs) are anti-inflammatory cytochrome P450-derived eicosanoids that are
      abundantly produced in the kidney and metabolized by soluble epoxide hydrolase
      (sEH; Ephx2) to less active dihydroxyeicosatrienoic acids. Genetic disruption of
      Ephx2 and chemical inhibition of sEH were used to test whether the anti
      inflammatory effects of EETs, and other lipid epoxide substrates of sEH, afford
      protection against cisplatin-induced nephrotoxicity. EET hydrolysis was
      significantly reduced in Ephx2(-/-) mice and was associated with an attenuation
      of cisplatin-induced increases in serum urea nitrogen and creatinine levels.
      Histological evidence of renal tubular damage and neutrophil infiltration was
      also reduced in the Ephx2(-/-) mice. Likewise, cisplatin had no effect on renal
      function, neutrophil infiltration, or tubular structure and integrity in mice
      treated with the potent sEH inhibitor 1-adamantan-1-yl-3-(1-methylsulfonyl
      piperidin-4-yl-urea) (AR9273). Consistent with the ability of EETs to interfere
      with nuclear factor-kappaB (NF-kappaB) signaling, the observed renoprotection was
      associated with attenuation of renal NF-kappaB activity and corresponding
      decreases in the expression of tumor necrosis factor (TNF) alpha, TNF receptor
      (TNFR) 1, TNFR2, and intercellular adhesive molecule-1 before the detection of
      tubular injury. These data suggest that EETs or other fatty acid epoxides can
      attenuate cisplatin-induced kidney injury and sEH inhibition is a novel
      renoprotective strategy.

PMID- 22414858
TI  - The alpha4beta2 nicotine acetylcholine receptor agonist ispronicline induces c
      Fos expression in selective regions of the rat forebrain.
AB  - The dominant nicotine acetylcholine receptor (nAChR) subtype in the brain is the
      pentameric receptor containing both alpha4 and beta2 subunits (alpha4beta2). Due
      to the lack of selective agonists it has not been ruled out what neuronal
      circuits that are stimulated after systemic administration with nicotine. We used
      the novel and selective alpha4beta2 receptor agonist ispronicline (10 and 30
      mg/kg s.c.) to localise the activated neurons in the rat forebrain using c-Fos
      immunoreactivity as a marker of immediate neuronal activity. In the hypothalamic
      paraventricular nucleus, a large increase of c-Fos-positive cells was found only
      within its medial part. In addition, an increased number of c-Fos-immunoreactive
      cells were observed in the central nucleus of the amygdala, and the dorsolateral
      part of the bed nucleus of the stria terminalis. The restricted distribution of c
      Fos to these areas, all of which are directly or indirectly involved in acute
      stress regulation after a single dose of ispronicline, supports earlier studies
      that the alpha4beta2 receptors are strongly involved in nicotine-dependent
      activation of the hypothalamo-pituitary adrenocortical axis.

PMID- 22414857
TI  - p38 mitogen-activated protein kinase is required for the antitumor activity of
      the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid.
AB  - 5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a potent vascular disrupting agent,
      selectively destroys established tumor vasculature, causing a rapid collapse in
      blood flow that ultimately leads to inhibition of tumor growth. Here, we
      demonstrate that p38 MAPK is critically involved in DMXAA-induced cytoskeleton
      reorganization in endothelial cells and tumor necrosis factor-alpha (TNF-alpha)
      production in macrophages, both of which were essential for DMXAA-induced
      vascular disruption. Inhibition of p38 mitogen-activated protein kinase (MAPK)
      significantly attenuated DMXAA-induced actin cytoskeleton reorganization in human
      umbilical vein endothelial cells and TNF-alpha production in macrophages. In
      vivo, p38 MAPK inhibition attenuated the immediate reduction in tumor blood flow
      induced by DMXAA treatment (<30 min) by inhibiting actin cytoskeleton
      reorganization in tumor vascular endothelial cells and blunted the long-lasting
      (>4 h) DMXAA-induced shutdown of the tumor vasculature by inhibiting intratumoral
      TNF-alpha production. These results indicate that p38 MAPK plays a critical role
      in DMXAA-induced endothelial cell cytoskeleton reorganization and TNF-alpha
      production, thus regulating DMXAA-induced antitumor activity.

PMID- 22414859
TI  - Thalamic cholinergic innervation is spared in Alzheimer disease compared to
      parkinsonian disorders.
AB  - There are two major sources of cholinergic projections in the brain. The nucleus
      basalis of Meynert provides the principal cholinergic input of the cortical
      mantle and the pedunculopontine nucleus-laterodorsal tegmental complex (PPN-LDTC;
      hereafter referred to as PPN) provides the major cholinergic input to the
      thalamus. Cortical cholinergic denervation has previously been shown to be part
      of Alzheimer and parkinsonian dementia but there is less information about
      subcortical thalamic cholinergic denervation. We investigated thalamic
      cholinergic afferent integrity by measuring PPN-Thalamic (PPN-Thal)
      acetylcholinesterase (AChE) activity via PET imaging in Alzheimer (AD), Parkinson
      disease without dementia (PD), Parkinson disease with dementia (PDD) and dementia
      with Lewy bodies (DLB). AD (n=13; mean age 75.4 +/- 5.5), PD (n=11; age 71.4 +/-
      6.4), PDD (n=6; age 70.8+/-4.7), DLB (n=6; age 68.0 +/- 8.6) and normal controls
      (NC; n=14; age 69.0 +/- 7.5) subjects underwent AChE [11C]-methyl-4-piperidinyl
      propionate (PMP) PET imaging. PPN-Thal PET data were analyzed using the Nagatsuka
      method. There were no significant differences in mean age between the groups
      (F=1.86, p=0.134). Kruskal-Wallis testing demonstrated a significant group effect
      for PPN-Thal AChE hydrolysis rates (F=9.62, p<0.0001). Compared to NC, reduced
      thalamic k3 hydrolysis rate was noted in subjects with PDD (-19.8%; AChE k3
      hydrolysis rates 0.1072 +/- 0.0143 min-1), DLB (-17.4%; 0.1103 +/- 0.0112 min-1)
      and PD (-12.8%; 0.1165 +/- 0.0114 min-1). Each of these 3 subgroups was
      statistically different from AD subjects (-0.7%; 0.1326 +/- 0.0095 min-1) who
      showed relatively spared thalamic k3 hydrolysis rates which were comparable to NC
      (0.1336 +/- 0.0142 min-1). Thalamic cholinergic denervation is present in PD,
      PDD, and DLB but not in AD. Neurodegenerative involvement of thalamic cholinergic
      afferent projections may contribute to disease-specific motor and cognitive
      abnormalities.

PMID- 22414860
TI  - Strategies for restoring vision to the blind: current and emerging technologies.
AB  - This paper reviews the current state of the art in the design of retinal
      prostheses that hope to restore vision to the blind. The progress and the
      challenges faced by electronic implants are discussed. Additionally, the emerging
      technologies in the field are also reviewed. These include optogenetics and
      chemical interfaces that interface to the neural system. These emerging fields
      have made tremendous progress in the last few years and offer new hope in the
      design of retinal prosthetic devices.

PMID- 22414862
TI  - 5-HT(1A) receptor and apoptosis contribute to interferon-alpha-induced
      "depressive-like" behavior in mice.
AB  - Interferon-alpha (IFN-alpha)-induced "depressive-like" behavior is a major
      limitation for the treatment of hepatitis C virus (HCV), especially for patients
      with psychiatric disorders. Recently, serotonin 1A (5-HT(1A)) receptor and
      cellular apoptosis are involved in mechanism(s) contributing to depression. To
      gain insight into this mechanism(s), we used C57BL/6J mice to examine the impact
      of IFN-alpha on the modulation of 5-HT(1A) receptor and cellular apoptosis and
      their relationship. Our results showed that repeated administration of IFN-alpha
      (6 MIU/kg, s.c.) induced "depressive-like" behavior of mice in the forced swim
      test, tail suspension test and sucrose preference test. Besides, the depressive
      mice exhibited a notable downregulation of 5-HT(1A) receptor and upregulation of
      cleaved caspase-3 and Bax/Bcl-2 ratio. These changes could be blocked by the 5
      HT(1A) receptor agonist 8-OH-DPAT (0.5 mg/kg, i.p., 30 min before IFN-alpha
      administration), but not by the standard antidepressant imipramine (10 mg/kg,
      i.p., 30 min before IFN-alpha administration) although both of them could
      ameliorate the depressive-like behavior of mice. These findings indicated that
      repeated injection with IFN-alpha provoked "depressive-like" behavior through
      cellular apoptosis, which could be ameliorated by the activation of 5-HT(1A)
      receptor.

PMID- 22414861
TI  - Real-time fMRI applied to pain management.
AB  - Current views recognize the brain as playing a pivotal role in the arising and
      maintenance of pain experience. Real-time fMRI (rtfMRI) feedback is a potential
      tool for pain modulation that directly targets the brain with the goal of
      restoring regulatory function. Though still relatively new, rtfMRI is a rapidly
      developing technology that has evolved in the last 15 years from simple proof of
      concept experiments to demonstrations of learned control of single and multiple
      brain areas. Numerous studies indicate rtfMRI feedback assisted control over
      specific brain areas may have applications including mood regulation, language
      processing, neurorehabilitation in stroke, enhancement of perception and
      learning, and pain management. We discuss in detail earlier work from our lab in
      which rtfMRI feedback was used to train both healthy controls and chronic pain
      patients to modulate anterior cingulate cortex (ACC) activation for the purposes
      of altering pain experience. Both groups improved in their ability to control ACC
      activation and modulate their pain with rtfMRI feedback training. Furthermore,
      the degree to which participants were able to modulate their pain correlated with
      the degree of control over ACC activation. We additionally review current
      advances in rtfMRI feedback, such as real-time pattern classification, that bring
      the technology closer to more comprehensive control over neural function.
      Finally, remaining methodological questions concerning the further development of
      rtfMRI feedback and its implications for the future of pain research are also
      discussed.

PMID- 22414863
TI  - Differential behavioral responses of the spontaneously hypertensive rat to
      methylphenidate and methamphetamine: lack of a rewarding effect of repeated
      methylphenidate treatment.
AB  - Several questions remain unanswered concerning the effects of long-term
      methylphenidate treatment in individuals with attention-deficit/hyperactivity
      disorder (ADHD). It has been speculated that repeated methylphenidate treatment
      may facilitate abuse of the drug or psychological dependence. In the present
      study, we conducted conditioned place preference (CPP) tests to investigate
      whether the repeated treatment of methylphenidate results to greater "liking" of
      the drug. We compared the effect of methylphenidate with that of methamphetamine,
      a drug with high abuse and dependence liability; also used as a treatment of
      ADHD. Prior to CPP tests, adolescent spontaneously hypertensive rats (SHR)
      (putative rodent model of ADHD) and Wistar rats (strain used to represent the
      "normal" heterogeneous population) were administered intraperitoneally with
      methylphenidate (1.25, 5 and 20 mg/kg) or methamphetamine (1.25 and 5 mg/kg) for
      14 days in their home cages. CPP tests were commenced and rats were conditioned
      with the two stimulants at the doses stated. We found that (1) repeated
      administration of methylphenidate and methamphetamine was rewarding in Wistar
      rats (2) stimulant-treated SHR showed CPP only to methamphetamine but not to
      methylphenidate. The observation that Wistar rats, but not SHR showed CPP to
      methylphenidate indicates vulnerability of "normal" individuals to
      methylphenidate abuse and dependence following repeated exposure or
      administration of the drug. The findings in SHR suggest the safety of
      methylphenidate as an ADHD intervention insofar as its behavioral effects are
      compared with those of methamphetamine, and to the extent that the SHR
      appropriately models ADHD in humans.

PMID- 22414864
TI  - Different involvement of ventral and dorsal norepinephrine pathways on
      norepinephrine reuptake inhibitor-induced locomotion and antidepressant-like
      effects in rats.
AB  - Two experiments were performed to investigate the involvements of ventral and
      dorsal norepinephrine bundle (VNB and DNB) in a selective norepinephrine reuptake
      inhibitor (NRI) reboxetine (RBX)-induced locomotion and antidepressant-like
      effects. Rats in the Experiment 1 received a local brain injection of 6
      hydroxydopamine (6-OHDA) or an intraperitoneal injection of N-(2-chloroethyl)-N
      ethyl-2-bromobenzylamine (DSP-4) to lesion their VNB or DNB, respectively. Acute
      effects of RBX (10 mg/kg, i.p.) on the locomotor activity and the forced swim
      test (FST) were measured 14 days after the lesion. In Experiment 2, activities of
      the norepinephrine transporter (NET) and the protein kinase C (PKC) in cortex,
      hippocampus, and locus coeruleus (LC) were detected by western blot after 14 days
      chronic RBX treatment. Results showed that the antidepressant-like effect of RBX
      was blocked in VNB lesion but augmented in DNB lesion, and was not relevant to
      the RBX-induced hypoactivity. Fourteen-days RBX treatment altered the activities
      of NET and PKC in LC but not hippocampus or cortex. The possible involvement of
      VNB and DNB in the RBX-induced antidepressant-like effect is discussed.

PMID- 22414865
TI  - Spike shape analysis of surface electromyographic activity in wrist flexor and
      extensor muscles of the world's fastest drummer.
AB  - Spike shape analysis (SSA) is a method to infer motor unit (MU) activity by
      examining interference pattern of surface electromyography (sEMG). SSA has
      succeeded to assess neuromuscular adaptations after dynamic training; however, it
      has not been used to assess muscle activities during the dynamic movements as
      seen in music performance. The present study used SSA to investigate sEMG
      activities of wrist flexor and extensor muscles in the winner of a contest to
      find the world's fastest drummer (WFD) during performing rhythmic wrist
      flexion/extension movements with one hand using a handheld drumstick. SSA
      measures of the WFD were compared with those in the two control groups: non
      drummers (NDs) and ordinary drummers (ODs). We found that the WFD showed
      significantly high mean spike frequency (MSF), short mean spike duration (MSD),
      and small mean number of peaks per spike (MNPPS) compared with the control
      groups. These results suggest that the WFD had exceptional MU activity such as
      higher MU discharge rate, more MU recruitment, and/or higher MU synchronization
      to achieve extraordinary fast 10-Hz drumming performance. SSA will be useful to
      investigate the muscle activity seen in music performance.

PMID- 22414866
TI  - Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on retinal
      dopaminergic system in mice.
AB  - The neurotoxins methamphetamine (METH) and MPTP are well-known for their effects
      on the nigrostriatal dopaminergic system and use in modeling neurodegenerative
      disorders such as Parkinson's disease. It is not well-known though, how METH or
      MPTP affects the visual system and specifically the retinal dopaminergic system.
      This study was designed to examine acute effects of multiple doses of METH and
      MPTP on the retinal dopaminergic system. Mice were exposed to either low- (LD) 10
      mg/kg total dose or high-dose (HD) 30 mg/kg total dose, of METH or MPTP and the
      retinal catecholaminergic system was analyzed by HPLC. METH produced no
      significant changes in dopamine (DA), its metabolites 3,4-dihydroxyphenylacetic
      acid (DOPAC) and homovanillic acid (HVA) or DA usage in the retina. LD-MPTP
      produced no change in DA level, but significantly decreased DOPAC and HVA. LD
      MPTP also significantly decreased DA usage as measured by the DOPAC/DA and HVA/DA
      ratios. HD-MPTP significantly decreased DA, DOPAC and HVA, but did not affect DA
      usage. Taken together these results suggest that inhibition of the DA
      metabolizing enzymes monoamine oxidase A (MAO) or catechol-O-methyl transferase
      (COMT) may take place at lower doses of MPTP treatment; conversely, higher doses
      of MPTP may cause decreases in DA, DOPAC and HVA through another mechanism.

PMID- 22414867
TI  - CCK-B receptor gene and response to cholecystokinin-tetrapeptide in healthy
      volunteers.
AB  - Recent investigations suggest that genes that confer risk for panic disorder (PD)
      may moderate response to panicogenic agents in healthy volunteers. Given the
      potential role of the central cholecystokinin receptor (CCKBR) (CT) polymorphism
      alleles 26 and 27 in PD, the present study attempted to discern if these alleles
      moderated panicogenic sensitivity to the CCKBR agonist, CCK-tetrapeptide (CCK-4),
      in healthy volunteers. The study group consisted of 92 men and women with no
      personal or family history of psychiatric illness. Participants provided blood
      samples for genotyping of the CCKBR alleles and they received a 25 MUg bolus
      injection of CCK-4. Behavioral, cardiovascular and hormonal responses to the
      peptide were assessed and analyzed with adjusted linear regression models.
      Carriers of the CCKBR alleles tended to have higher levels of pre-challenge
      anxiety and significantly higher levels of anxiety sensitivity and introversion
      than those without the alleles. However, they did not exhibit an enhanced
      panicogenic response to CCK-4. Overall, our findings do not demonstrate a role of
      these alleles in modulating CCK-4's panicogenicity. The significant association
      between the risk alleles and anxiety-related personality traits is intriguing and
      further exploration of this association is merited.

PMID- 22414868
TI  - Silver cluster-biomolecule hybrids: from basics towards sensors.
AB  - We focus on the functional role of small silver clusters in model hybrid systems
      involving peptides in the context of a new generation of nanostructured materials
      for biosensing. The optical properties of hybrids in the gas phase and at support
      will be addressed with the aim to bridge fundamental and application aspects. We
      show that extension and enhancement of absorption of peptides can be achieved by
      small silver clusters due to the interaction of intense intracluster excitations
      with the pi-pi* excitations of chromophoric aminoacids. Moreover, we demonstrate
      that the binding of a peptide to a supported silver cluster can be detected by
      the optical fingerprint. This illustrates that supported silver clusters can
      serve as building blocks for biosensing materials. Moreover, the clusters can be
      used simultaneously to immobilize biomolecules and to increase the sensitivity of
      detection, thus replacing the standard use of organic dyes and providing label
      free detection. Complementary to that, we show that protected silver clusters
      containing a cluster core and a shell liganded by thiolates exhibit absorption
      properties with intense transitions in the visible regime which are also suitable
      for biosensing applications.

PMID- 22414869
TI  - Modafinil inhibits K(Ca)3.1 currents and muscle contraction via a cAMP-dependent
      mechanism.
AB  - Modafinil has been used as a psychostimulant for the treatment of narcolepsy.
      However, its primary mechanism of action remains elusive. Therefore, we examined
      the effects of modafinil on K(Ca)3.1 channels and vascular smooth muscle
      contraction. K(Ca)3.1 currents and channel activity were measured using a voltage
      clamp technique and inside-out patches in mouse embryonic fibroblast cell line,
      NIH-3T3 fibroblasts. Intracellular adenosine 3',5'-cyclic monophosphate (cAMP)
      concentration was measured, and the phosphorylation of K(Ca)3.1 channel protein
      was examined using western blotting in NIH-3T3 fibroblasts and/or primary
      cultured mouse aortic smooth muscle cells (SMCs). Muscle contractions were
      recorded from mouse aorta and rat pulmonary artery by using a myograph developed
      in-house. Modafinil was found to inhibit K(Ca)3.1 currents in a concentration
      dependent manner, and the half-maximal inhibition (IC(50)) of modafinil for the
      current inhibition was 6.8 +/- 0.7 nM. The protein kinase A (PKA) activator
      forskolin also inhibited K(Ca)3.1 currents. The inhibitory effects of modafinil
      and forskolin on K(Ca)3.1 currents were blocked by the PKA inhibitors PKI(14-22)
      or H-89. In addition, modafinil relaxed blood vessels (mouse aorta and rat
      pulmonary artery) in a concentration-dependent manner. Modafinil increased cAMP
      concentrations in NIH-3T3 fibroblasts or primary cultured mouse aortic SMCs and
      phosphorylated K(Ca)3.1 channel protein in NIH-3T3 fibroblasts. However, open
      probability and single-channel current amplitudes of K(Ca)3.1 channels were not
      changed by modafinil. From these results, we conclude that modafinil inhibits
      K(Ca)3.1 channels and vascular smooth muscle contraction by cAMP-dependent
      phosphorylation, suggesting that modafinil can be used as a cAMP-dependent
      K(Ca)3.1 channel blocker and vasodilator.

PMID- 22414870
TI  - Colonization of Euprymna scolopes squid by Vibrio fischeri.
AB  - Specific bacteria are found in association with animal tissue. Such host
      bacterial associations (symbioses) can be detrimental (pathogenic), have no
      fitness consequence (commensal), or be beneficial (mutualistic). While much
      attention has been given to pathogenic interactions, little is known about the
      processes that dictate the reproducible acquisition of beneficial/commensal
      bacteria from the environment. The light-organ mutualism between the marine Gram
      negative bacterium V. fischeri and the Hawaiian bobtail squid, E. scolopes,
      represents a highly specific interaction in which one host (E. scolopes)
      establishes a symbiotic relationship with only one bacterial species (V.
      fischeri) throughout the course of its lifetime. Bioluminescence produced by V.
      fischeri during this interaction provides an anti-predatory benefit to E.
      scolopes during nocturnal activities, while the nutrient-rich host tissue
      provides V. fischeri with a protected niche. During each host generation, this
      relationship is recapitulated, thus representing a predictable process that can
      be assessed in detail at various stages of symbiotic development. In the
      laboratory, the juvenile squid hatch aposymbiotically (uncolonized), and, if
      collected within the first 30-60 minutes and transferred to symbiont-free water,
      cannot be colonized except by the experimental inoculum. This interaction thus
      provides a useful model system in which to assess the individual steps that lead
      to specific acquisition of a symbiotic microbe from the environment. Here we
      describe a method to assess the degree of colonization that occurs when newly
      hatched aposymbiotic E. scolopes are exposed to (artificial) seawater containing
      V. fischeri. This simple assay describes inoculation, natural infection, and
      recovery of the bacterial symbiont from the nascent light organ of E. scolopes.
      Care is taken to provide a consistent environment for the animals during
      symbiotic development, especially with regard to water quality and light cues.
      Methods to characterize the symbiotic population described include (1)
      measurement of bacterially-derived bioluminescence, and (2) direct colony
      counting of recovered symbionts.

PMID- 22414871
TI  - Lumbar intervertebral disc degeneration associated with axial and radiating low
      back pain in ageing SPARC-null mice.
AB  - Chronic low back pain (LBP) is a complex, multifactorial disorder with unclear
      underlying mechanisms. In humans and rodents, decreased expression of secreted
      protein acidic rich in cysteine (SPARC) is associated with intervertebral disc
      (IVD) degeneration and signs of LBP. The current study investigates the
      hypothesis that IVD degeneration is a risk factor for chronic LBP. SPARC-null and
      age-matched control mice ranging from 6 to 78 weeks of age were evaluated in this
      study. X-ray and histologic analysis revealed reduced IVD height, increased
      wedging, and signs of degeneration (bulging and herniation). Cutaneous
      sensitivity to cold, heat, and mechanical stimuli were used as measures of
      referred (low back and tail) and radiating pain (hind paw). Region specificity
      was assessed by measuring icilin- and capsaicin-evoked behaviour after
      subcutaneous injection into the hind paw or upper lip. Axial discomfort was
      measured by the tail suspension and grip force assays. Motor impairment was
      determined by the accelerating rotarod. Physical function was evaluated by
      voluntary activity after axial strain or during ambulation with forced lateral
      flexion. SPARC-null mice developed (1) region-specific, age-dependent
      hypersensitivity to cold, icilin, and capsaicin (hind paw only), (2) axial
      discomfort, (3) motor impairment, and (4) reduced physical function. Morphine (6
      mg/kg, i.p.) reduced cutaneous sensitivity and alleviated axial discomfort in
      SPARC-null mice. Ageing SPARC-null mice mirror many aspects of the complex and
      challenging nature of LBP in humans and incorporate both anatomic and functional
      components of the disease. The current study supports the hypothesis that IVD
      degeneration is a risk factor for chronic LBP.

PMID- 22414872
TI  - Recent advances and clinical application of erythropoietin and erythropoiesis
      stimulating agents.
AB  - Erythropoietin (EPO) is an essential glycoprotein that facilitates red blood cell
      maturation from erythroid progenitors and mediates erythropoiesis. The use of
      recombinant human EPO (rhEPO) dramatically changed management of anemic patients
      with chronic kidney disease and improved their quality of life. EPO is mainly
      produced in the fetal liver and the postnatal kidney, although the molecular
      determinants for tissue-specific expression are elusive. Meanwhile, recent
      advances established a role of hypoxia-inducible factors (HIF) in
      transcriptionally upregulating EPO in hypoxia. Out of three HIF- isoforms, HIF-2
      appears to play a central role. Prolyl hydroxylase domain-containing protein
      (PHD), a key regulator connecting oxygen availability and HIF-alpha expression,
      is also involved in hypoxic induction of EPO mRNA and the precise roles of PHD
      paralogs in erythropoiesis are now beginning to be uncovered. On the other hand,
      widespread expression of EPO receptors (EPOR) beyond erythroid progenitors led to
      the discovery of non-hematopoietic, pleiotropic roles of EPO in the brain, the
      heart and the kidney. The precise signal transduction pathways of pleiotropic EPO
      remain unclear, but carbamylated EPO, which fails to bind to the canonical EPOR
      homodimers or transduce the JAK2-STAT5 signaling, conferred organ protection
      through multimeric receptors composed of EPO-R and the common beta subunit
      (betaCR). The clinical benefit of normalization of anemia in pre-dialysis CKD by
      EPO therapy is controversial and recent large-scale, randomized-controlled trials
      do not favor normalization of anemia by EPO in improving cardiovascular as well
      as renal outcomes. The optimal EPO therapy should be determined based on the
      clinical context of individual patients.

PMID- 22414873
TI  - Mesangial cell biology.
AB  - Mesangial cells originate from the metanephric mesenchyme and maintain structural
      integrity of the glomerular microvascular bed and mesangial matrix homeostasis.
      In response to metabolic, immunologic or hemodynamic injury, these cells undergo
      apoptosis or acquire an activated phenotype and undergo hypertrophy,
      proliferation with excessive production of matrix proteins, growth factors,
      chemokines and cytokines. These soluble factors exert autocrine and paracrine
      effects on the cells or on other glomerular cells, respectively. MCs are primary
      targets of immune-mediated glomerular diseases such as IGA nephropathy or
      metabolic diseases such as diabetes. MCs may also respond to injury that
      primarily involves podocytes and endothelial cells or to structural and genetic
      abnormalities of the glomerular basement membrane. Signal transduction and
      oxidant stress pathways are activated in MCs and likely represent integrated
      input from multiple mediators. Such responses are convenient targets for
      therapeutic intervention. Studies in cultured MCs should be supplemented with in
      vivo studies as well as examination of freshly isolated cells from normal and
      diseases glomeruli. In addition to ex vivo morphologic studies in kidney cortex,
      cells should be studied in their natural environment, isolated glomeruli or even
      tissue slices. Identification of a specific marker of MCs should help genetic
      manipulation as well as selective therapeutic targeting of these cells.
      Identification of biological responses of MCs that are not mediated by the renin
      angiotensin system should help development of novel and effective therapeutic
      strategies to treat diseases characterized by MC pathology.

PMID- 22414875
TI  - Effects of testosterone supplementation on clinical and rehabilitative outcomes
      in older men undergoing on-pump CABG.
AB  - Testosterone levels decrease with age. This decline is steeper during "critical
      illnesses". Cardiac surgery is a particular representative model of major
      clinical condition producing stress responses similar to those observed during
      severe nonsurgical illness. Cardiac revascularization with extracorporeal
      circulation is characterized by marked postoperative complications such as
      insulin resistance, a pro-inflammatory state, acute anemia and renal dysfunction.
      These phenomena are more evident in older subjects, who are particularly
      vulnerable in the post-operative state, a condition that has been recently termed
      as "acute postoperative frailty". We recently showed that in older men with low
      ejection fraction undergoing cardiac revascularization with extracorporeal
      circulation, there is a profound decline in anabolic hormones, including
      testosterone. After surgery testosterone concentration frequently declines to
      less than 200 ng/dl, a situation suggestive of overt hypogonadism. Since men with
      low testosterone levels have a high probability of developing mobility
      limitations, we considered this a rationale for the perioperative use of
      testosterone treatment in older men undergoing cardiac revasularization surgery.
      We hypothesized that testosterone supplementation at this time might attenuate
      the impressive post-surgical catabolic hormonal milieu. The aim of this
      manuscript is to elucidate an ongoing randomized clinical trial in older men (70+
      years old) undergoing elective cardiovascular revascularization with
      extracorporeal circulation. This randomized clinical trial will evaluate the
      effects of intramuscular testosterone administration on clinical and functional
      outcomes in this population. The study will also address potential mechanisms
      underlying the expected beneficial effects of testosterone supplementation
      including improvement of insulin sensitivity, markers of inflammatory status and
      improved hemoglobin levels.

PMID- 22414874
TI  - Notch signaling in diabetic nephropathy.
AB  - Notch signaling is an evolutionarily conserved cell-cell signaling system that
      controls the fate of cells during development. In this review, we will summarize
      the literature that notch signaling during development controls nephron number
      and segmentation and therefore could influence kidney disease susceptibility. We
      will also review the evidence that Notch is reactivated in adult-onset diabetic
      kidney disease where it promotes the development of nephropathy including
      glomerulopathy, tubulointerstitial fibrosis and possibly arteriopathy and
      inflammation. Finally, we will review the evidence that blockade of pathogenic
      Notch signaling alters the natural history of diabetic nephropathy and thus could
      represent a novel therapeutic approach to the management of diabetic kidney
      disease.

PMID- 22414876
TI  - Alpha-1-antitrypsin acts as a preeclampsia-related protein: a proteomic study.
AB  - AIMS: To screen the preeclampsia-related protein by proteomics. METHODS:
      Proteomics was performed to identify differential protein expression profiles
      between normal full-term pregnancy, early-onset severe preeclampsia (ES-PE) or
      late-onset severe preeclampsia (LS-PE; n = 10 per group). Real-time quantitative
      PCR and immunohistochemistry were conducted to confirm the expression of alpha(1)
      antitrypsin (alpha(1)-AT) in the decidual tissues of different subjects. ELISA
      was employed to detect the alpha(1)-AT content in the peripheral blood of 90
      women (n = 30 per group). RESULTS: We successfully constructed two-dimensional
      electrophoresis maps of decidual tissues, and a total of 20 differentially
      expressed proteins were identified. The alpha(1)-AT expression was different
      among the three groups. The normal full-term pregnancy women expressed the most
      alpha(1)-AT, and the LS-PE women expressed the least amount of alpha(1)-AT. The
      difference in the alpha(1)-AT expression was consistent with the proteomics data.
      The peripheral alpha(1)-AT content was the highest in the normal full-term
      pregnancy group (1.85 +/- 0.15 g/l), moderate in the ES-PE group (0.77 +/- 0.14
      g/l) and lowest in the LS-PE group (0.42 +/- 0.07 g/l; p < 0.05). CONCLUSION:
      Using 2D PAGE, we identified twenty proteins with significantly altered
      expression in PE. These differentially expressed proteins include prevention
      protein, in which alpha(1)-AT is downregulated in PE.

PMID- 22414877
TI  - Novel tagging SNP rs1495741 and 2-SNPs (rs1041983 and rs1801280) yield a high
      prediction of the NAT2 genotype in HapMap samples.

PMID- 22414878
TI  - Patent ductus arteriosus: mechanisms and management.

PMID- 22414879
TI  - Mechanisms for ductus arteriosus closure.
AB  - Closure of the ductus arteriosus at birth is a complex phenomenon being
      conditioned by antenatal events and progressing in preprogrammed steps.
      Functional at first, narrowing of the vessel is determined by 2 overlapping
      processes--removal of the prostaglandin E(2)-based relaxation sustaining prenatal
      patency and activation of a constrictor mechanism by the natural rise in blood
      oxygen tension. Two schemes have been proposed for oxygen action--one involving a
      cytochrome P450 hemoprotein (sensor)/endothelin-1 (effector) complex and the
      other a set of voltage-gated K(+) channels. These proposals, however, are not
      mutually exclusive. Structural closure follows the constriction through a
      remodeling process initiated antenatally with the development of intimal cushions
      and completed postnatally by a host of humoral and mechanical stimuli. Research
      in this area has already provided clinical applications. Nevertheless, management
      of premature infants with persistent ductus remains troublesome and calls for an
      alternative approach to the prostaglandin E(2) inhibitors now in use. Studies in
      progress on the oxygen-sensing system may lead to a definitive solution for this
      problem.

PMID- 22414880
TI  - Genetics of patent ductus arteriosus susceptibility and treatment.
AB  - The ductus arteriosus is a vital fetal structure designed to close shortly after
      birth. Although many physiologic and pharmacologic investigations have
      characterized the closure of this structure, genetic studies of persistent
      patency of the ductus arteriosus (patent ductus arteriosus, PDA) are relatively
      recent. Progress in the identification of specific genes associated with PDA is
      well behind that of many adult-onset diseases because of several reasons ranging
      from the lack of large biorepositories for this unique population to the belief
      that any genetic contribution to PDA is minimal. Viewing the PDA as a complex,
      developmentally influenced disease with both genetic and environmental risk
      factors has resulted in initial successes in some genetic studies. We will
      introduce several genetic approaches, which have been or are currently being
      applied to the study of PDA, that have been successful in identifying
      polymorphisms associated with adult diseases. Genetic investigations of PDA will
      be discussed with respect to heritability, in general, and to specific risk
      genes. Several animal models that have been used to study PDA-related genes will
      also be presented. Further advances in discovering genetic variation causing PDA
      will drive the more rational use of current therapies, and may help identify
      currently unknown targets for future therapeutic manipulation.

PMID- 22414881
TI  - The ductus arteriosus: a refined approach!
AB  - Although ongoing patency of the ductus arteriosus is common in small extremely
      preterm infants, consensus is lacking regarding its clinical significance and
      treatment strategies. Literature regarding likelihood of spontaneous closure,
      impact on neonatal morbidity and long-term outcomes, and adverse effects of
      intervention has led to uncertainty as to the best course of action. Enhancing
      the determination of hemodynamic significance and refining patient selection for
      therapeutic intervention will streamline the decision-making process. Targeted
      neonatal echocardiography performed by the clinician has gained popularity
      worldwide, and preliminary data show that it has the potential to optimize
      patient outcomes. We review the arguments for and against medical and surgical
      therapy, explore how targeted neonatal echocardiography used in conjunction with
      biomarkers may refine the treatment approach, and consider future directions in
      the field.

PMID- 22414882
TI  - Diagnosis of the preterm patent ductus arteriosus: clinical signs, biomarkers, or
      ultrasound?
AB  - The current uncertainty in relation to treatment of the preterm patent ductus
      arteriosus reflects limitations to our understanding of the pathophysiology of
      ductal shunting, most particularly which ducts matter to which babies and when
      they matter. Doppler ultrasound offers a pragmatic tool with which to assess
      ductal patency and shunt significance and to allow prediction of spontaneous and
      therapeutic closure. Biomarkers, such as B-type natriuretic peptide, and clinical
      signs may have a diagnostic role where ultrasound is not available and also
      possibly as an adjunct to echocardiography in determining the pathophysiological
      impact of a ductal shunt in an individual baby.

PMID- 22414884
TI  - Managing the patent ductus arteriosus in the premature neonate: a new look at
      what we thought we knew.
AB  - Over recent years, the clinical approach to patency of the ductus arteriosus in
      the premature neonate has been the subject of intensive reevaluation. What had
      once been considered inherently obvious is no longer to be taken for granted. In
      this review we will focus on some of the controversies surrounding various
      aspects of the pharmacologic treatment regimens for patent ductus arteriosus
      closure. The pros and cons of prophylactic vs therapeutic indomethacin, of early
      vs late therapy, of high- vs low-dose indomethacin, of single vs multiple courses
      of treatment, and of ibuprofen vs indomethacin will be considered. In addition,
      the possibility that patency of the ductus arteriosus is merely a physiological
      manifestation of extreme prematurity, and thus does not necessarily need to be
      therapeutically closed, has become a viable approach in some cases. As such, we
      will examine echocardiographic and biochemical criteria aimed at determining the
      clinical and hemodynamic significance of ductal shunting, and thereby of the need
      to treat. Finally, we speculate on potential therapeutic directions for the
      future, including individualized treatment regimens and multidrug treatment
      cocktails for those who fail initial monodrug therapy.

PMID- 22414883
TI  - Patent ductus arteriosus: are current neonatal treatment options better or worse
      than no treatment at all?
AB  - Although a moderate-sized patent ductus arteriosus (PDA) needs to be closed by
      the time a child is 1-2 years old, there is great uncertainty about whether it
      needs to be closed during the neonatal period. Although 95% of neonatologists
      believe that a moderate-sized PDA should be closed if it persists in infants
      (born before 28 weeks) who still require mechanical ventilation, the number of
      neonatologists who treat a PDA when it occurs in infants who do not require
      mechanical ventilation varies widely. Both the high likelihood of spontaneous
      ductus closure and the absence of randomized controlled trials, specifically
      addressing the risks and benefits of neonatal ductus closure, add to the current
      uncertainty. New information suggests that early pharmacologic treatment has
      several important short-term benefits for the preterm newborn. By contrast,
      ductus ligation, while eliminating the detrimental effects of a PDA on lung
      development, may create its own set of morbidities that counteract many of the
      benefits derived from ductus closure.

PMID- 22414885
TI  - Pros and cons of patent ductus arteriosus ligation: hemodynamic changes and other
      morbidities after patent ductus arteriosus ligation.
AB  - Although surgical ligation of a persistent patent ductus arteriosus resolves the
      adverse hemodynamic consequences of the systemic-to-pulmonary shunt and may
      confer some long-term benefits, it is also associated with both immediate and
      long-term negative effects. The population that benefits from or is harmed by the
      procedure is not clearly defined. Although indiscriminate ligation of the patent
      ductus arteriosus in all patients is not supported by the available information,
      the recent suggestion declaring the ductus harmless is not supported either. As
      we await the results of appropriately designed randomized control studies to
      define the indications for ligation, we must use clinical and echocardiographic
      indicators of a hemodynamically significant ductus arteriosus and thoughtful
      assessment of each individual patient to help guide us in addressing this complex
      problem.

PMID- 22414886
TI  - The patent ductus arteriosus in term infants, children, and adults.
AB  - During fetal life, the ductus arteriosus is a normal and essential structure that
      connects the pulmonary artery to the distal aortic arch, permitting right
      ventricular ejection into the aorta. After birth, with commencement of pulmonary
      blood flow and a 2-ventricle circulation, a variety of physiological and
      biochemical signals normally result in complete closure of the ductus. Persistent
      patency of the ductus arteriosus may impair systemic cardiac output and result in
      deleterious effects on the cardiovascular system and lungs. Although surgery is
      still the treatment of choice for most premature infants with patent ductus
      arteriosus (PDA), transcatheter techniques have largely supplanted surgery for
      closure of PDA in children and adults. This article is a review of the PDA in
      term infants, children, and adults, with focus on the clinical manifestations and
      management.

PMID- 22414887
TI  - Synthesis of core/shell spinel  ferrite/carbon nanoparticles with  enhanced
      cycling stability for lithium ion  battery anodes.
AB  - Monodispersed core/shell spinel ferrite/carbon nanoparticles are formed by
      thermolysis of metal (Fe3+, Co2+) oleates followed by carbon coating. The phase
      and morphology of nanoparticles are characterized by x-ray diffraction and
      transmission electron microscopy. Pure Fe3O4 and CoFe2O4 nanoparticles are
      initially prepared through thermal decomposition of metal-oleate precursors at
      310 degrees C and they are found to exhibit poor electrochemical performance
      because of the easy aggregation of nanoparticles and the resulting increase in
      the interparticle contact resistance. In contrast, uniform carbon coating of
      Fe3O4 and CoFe2O4 nanoparticles by low-temperature (180 degrees C) decomposition
      of malic acid allowed each nanoparticle to be electrically wired to a current
      collector through a conducting percolative path. Core/shell Fe3O4/C and CoFe2O4/C
      nanocomposite electrodes show a high specific capacity that can exceed 700 mAh g(
      1) after 200 cycles, along with enhanced cycling stability.

PMID- 22414888
TI  - Exercise response in hypertrophic cardiomyopathy: blunted left ventricular
      deformational and twisting reserve with altered systolic-diastolic coupling.
AB  - BACKGROUND: Abnormal left ventricular (LV) deformational mechanics have been
      demonstrated in patients with hypertrophic cardiomyopathy (HCM) at rest, but
      there is a lack of information on their adaptation to exercise. The aim of this
      study was to assess the adaptability of LV strains and torsional mechanics during
      exercise in HCM patients. METHODS AND RESULTS: Twenty nonobstructive HCM patients
      (age, 48.3+/-12.3 years; 14 men) and 20 control subjects underwent speckle
      tracking echocardiographic measurement of longitudinal, radial, and
      circumferential strains, systolic twist, and diastolic untwisting rate (UTR) at
      rest and submaximal exercise. HCM patients showed lower resting longitudinal (
      15.7+/-5.0% versus -19.4+/-2.6%, P<0.001) and radial (38.1+/-11.3% versus 44.7+/
      14.4%, P<0.05) strains but higher circumferential strain (-21.9+/-4.0% versus 
      18.8+/-2.3%, P<0.05) and twist (15.7+/-3.6 degrees  versus 9.3+/-2.6 degrees ,
      P<0.0001) than control subjects. Exercise induced an increase in all strains in
      control subjects but only a moderate increase in longitudinal strain (to -18.4+/
      5.0%), without significant changes in radial and circumferential strains or twist
      in HCM patients. Exercise peak UTR was lower (-119.0+/-31.5 degrees /s versus 
      137.3+/-41.1 degrees /s) and occurred later (137+/-18% versus 125+/-11% systolic
      time, P<0.05) in HCM than in control subjects. A significant relationship between
      twist and UTR was obtained in control subjects (beta=-0.0807, P<0.001) but not in
      HCM patients (beta=-0.0051, P=0.68). CONCLUSIONS: HCM patients had severely
      limited strain adaptability and no LV twisting reserve at exercise. They had
      reduced and delayed UTR with reduced systolic-diastolic coupling efficiency by
      twist-untwist mechanics.

PMID- 22414889
TI  - Are dieting-related cognitive impairments a function of iron status?
AB  - The aim of the present study was to investigate whether the impairments in
      cognitive function observed in unsupported dieting are related to compromised Fe
      status. During a non-clinical intervention, overweight participants (age: 18-45
      years, BMI: 25-30 kg/m2) either participated in a commercially available weight
      loss regimen (n 14), dieted without support (n 17) or acted as a non-dieting
      control group (n 14) for a period of 8 weeks. Measurements of cognitive function
      and blood chemistry were taken at a pre-diet baseline, after 1 week and 8 weeks
      of dieting. After 1 week, unsupported dieters displayed impaired verbal memory,
      executive function and slower reaction speeds than the other two groups, this
      difference disappearing by the end of the study. There were no significant group
      related changes in blood chemistry over the course of the study, although there
      were group-related changes in a number of self-reported food-related cognitions.
      In conclusion, impaired cognition among unsupported dieters is not due to
      compromised Fe status and is most likely to result from psychological variables.

PMID- 22414891
TI  - Current world literature.

PMID- 22414890
TI  - Association between single nucleotide polymorphisms in p53 and abortion in
      Thoroughbred mares.
AB  - Single nucleotide polymorphisms (SNPs) in the p53 gene have been studied
      extensively in humans. The aims of this study were to determine the frequency of
      the Arg/Pro SNP in p53 in Thoroughbred mares on one stud in Brazil and to
      correlate p53 genotypes with reproductive performance. SNPs were detected by PCR
      restriction fragment length polymorphism in blood samples from 105 horses and
      confirmed by sequencing. The allele frequency in Thoroughbred mares at codon 72
      in exon 4 was 73.3% Arg/Pro, 17.1% Arg/Arg and 9.6% Pro/Pro. The presence of
      Arg/Pro was significantly associated with abortion (P=0.02), while Pro/Pro mares
      had a lower probability of abortion (P<0.05). Using a logistic regression model,
      the dominance effect was significant (P=0.044; odds ratio 7.94) for abortion and
      additive effects were not significant (P=0.26). p53 may play a role in equine
      reproduction.

PMID- 22414894
TI  - Association between the self-perception period of lower urinary tract symptoms
      and the International Prostate Symptom Score.
AB  - OBJECTIVES: The timing of visiting a hospital after self-perception of lower
      urinary tract symptoms (LUTS) is different between individuals. The association
      between the self-perception period (S-PP) of LUTS and the progression of LUTS has
      seldom been documented. The aim of this study was to investigate the association
      between the S-PP of LUTS and the International Prostate Symptom Score (IPSS).
      SUBJECTS AND METHODS: This was a cross-sectional study comprising 267 men aged 40
      years and older who participated in a prostate examination survey between
      February and May 2009. Survey questionnaires included items on the IPSS, the S
      PPs of seven individual LUTSs assessed in the IPSS. RESULTS: The S-PP of LUTS
      became significantly longer as the severity of LUTS increased. Of the seven
      symptoms, a weak urinary stream and nocturia showed longer S-PPs than others.
      Partial correlation between the S-PP and IPSS showed a statistically significant
      positive correlation. Linear regression analysis showed a statistically
      significant relationship that unstandardized coefficients included 0.051 and
      0.005 for IPSS and quality of life. CONCLUSIONS: These findings suggest that the
      S-PP is an independent risk factor for LUTS progression. S-PPs have to be
      considered for treatment or prevention of LUTS.

PMID- 22414895
TI  - Cell signalling: Building strong muscles.

PMID- 22414896
TI  - Apoptosis: A lipid trigger of MOMP.

PMID- 22414898
TI  - Combining form with function--the dawn of phosphole-based functional materials.
AB  - Phosphole-based pi-conjugated compounds have recently attracted significant
      attention due their unique electronic properties. It is now well established that
      the versatile phosphorus chemistry offers great opportunities for efficient fine
      tuning of the properties of pi-conjugated systems from a fundamental point of
      view; a feature that pure carbon-based pi-conjugated materials cannot provide.
      This perspective highlights the recent progress using phosphole-based pi
      conjugated building blocks towards applied materials with multiple and diverse
      functionalities.

PMID- 22414899
TI  - Deterioration of bulk heterojunction organic photovoltaic devices by a minute
      amount of oxidized fullerene.
AB  - A chemical model of deterioration of a bulk heterojunction organic solar cell
      containing a photooxidized product of 1,4
      bis(dimethylphenylsilylmethyl)[60]fullerene suggests that molecular oxygen
      degrades device performance by two mechanisms.

PMID- 22414897
TI  - Transcriptional integration of metabolism by the nuclear sterol-activated
      receptors LXR and FXR.
AB  - Nuclear receptors are integrators of hormonal and nutritional signals, mediating
      changes to metabolic pathways within the body. Given that modulation of lipid and
      glucose metabolism has been linked to diseases including type 2 diabetes, obesity
      and atherosclerosis, a greater understanding of pathways that regulate metabolism
      in physiology and disease is crucial. The liver X receptors (LXRs) and the
      farnesoid X receptors (FXRs) are activated by oxysterols and bile acids,
      respectively. Mounting evidence indicates that these nuclear receptors have
      essential roles, not only in the regulation of cholesterol and bile acid
      metabolism but also in the integration of sterol, fatty acid and glucose
      metabolism.

PMID- 22414900
TI  - Density, DSC, X-ray and NMR measurements through the gel and lamellar phase
      transitions of 1-myristoyl-2-stearoyl-sn-glycero-3-phosphatidylcholine (MSPC) and
      1-stearoyl-2-myristoyl-sn-glycero-3-phosphatidylcholine (SMPC): observation of
      slow relaxation processes and mechanisms of phase transitions.
AB  - Dialkyl lecithin dispersions in water exhibit two phase transitions upon cooling
      from the lamellar phase (L(alpha)). At the main transition (T(M)) the L(alpha)
      phase changes to a ripple (gel) phase (P(beta')) which then transforms to a
      second gel phase (L(beta')) at the "pretransition" (T(P)). We have made accurate
      density measurements through the various phases for two lecithins having unequal
      chains: 1-myristoyl-2-stearoyl-sn-glycero-3-phosphatidylcholine (MSPC) and 1
      stearoyl-2-myristoyl-sn-glycero-3-phosphatidylcholine (SMPC). The measurements
      were carried out over five heat/cool cycles from 5 to 55  degrees C, followed by
      cooling back to 5  degrees C. The samples were then held at 50  degrees C for 24
      hours, followed by a further three cool/heat cycles. For SMPC we observe an
      increase in density of the gel phases over the first 5 cycles, followed by much
      smaller changes after incubation at 50  degrees C. The lamellar phase also shows
      an increase in density, albeit much smaller. This parallels the behaviour of 1,2
      di-palmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and 1,2-di-myristoyl-sn
      glycero-3-phosphatidylcholine (DMPC) reported earlier (Jones et al., Liquid
      Crystals 32, 1465 (2005)). For MSPC we observe a decrease in density within the
      gel phases while T(P) almost disappears after the first cycle. The lamellar phase
      shows little evidence of any change with each cycle. Within the lamellar phases
      there is a marked reduction in density on approaching T(M), which is attributed
      to the formation of transitory gel phase domains. Additional measurements by DSC
      and X-ray diffraction show that the changes in densities are not accompanied by
      large changes in transition enthalpies or phase structures. NMR data indicate
      that the pretransitional event within the L(alpha) phase is accompanied by
      ordering of the alkyl chains. The results indicate that the exact nature of the
      lipid alkyl chains could play a key role in the formation of gel phase patches
      within membrane bilayers. Their detailed chemical structures merit more attention
      than by simply assuming a uniform "bending energy" to describe the behaviour.

PMID- 22414893
TI  - The importance of early brain injury after subarachnoid hemorrhage.
AB  - Aneurysmal subarachnoid hemorrhage (aSAH) is a medical emergency that accounts
      for 5% of all stroke cases. Individuals affected are typically in the prime of
      their lives (mean age 50 years). Approximately 12% of patients die before
      receiving medical attention, 33% within 48 h and 50% within 30 days of aSAH. Of
      the survivors 50% suffer from permanent disability with an estimated lifetime
      cost more than double that of an ischemic stroke. Traditionally, spasm that
      develops in large cerebral arteries 3-7 days after aneurysm rupture is considered
      the most important determinant of brain injury and outcome after aSAH. However,
      recent studies show that prevention of delayed vasospasm does not improve outcome
      in aSAH patients. This finding has finally brought in focus the influence of
      early brain injury on outcome of aSAH. A substantial amount of evidence indicates
      that brain injury begins at the aneurysm rupture, evolves with time and plays an
      important role in patients' outcome. In this manuscript we review early brain
      injury after aSAH. Due to the early nature, most of the information on this
      injury comes from animals and few only from autopsy of patients who died within
      days after aSAH. Consequently, we began with a review of animal models of early
      brain injury, next we review the mechanisms of brain injury according to the
      sequence of their temporal appearance and finally we discuss the failure of
      clinical translation of therapies successful in animal models of aSAH.

PMID- 22414901
TI  - VEGF target in HHT lung patients: the role of bevacizumab as a possible
      alternative to embolization.

PMID- 22414902
TI  - Pandemic influenza a in residential summer camps--Maine, 2009.
AB  - OBJECTIVE: The aim of this study was to evaluate the preparedness for and
      response of Maine summer camps to the 2009 pandemic influenza H1N1 (pH1N1).
      METHODS: We conducted a retrospective web-based survey of the Maine Youth Camping
      Foundation members at the end of the 2009 camping season. The outcome measures
      were responses to the pandemic including educational efforts, isolation practices
      and antiviral usages as well as percentage of influenza-like illness (ILI) and
      laboratory-confirmed influenza outbreaks among Maine residential summer camps.
      RESULTS: Of 107 residential camps queried, 91 (85%) responded. Although 43 (47%)
      of 91 camps reported cases of ILI, and 19 (21%) had outbreaks (ie, 3 or more
      confirmed cases of pH1N1), no respondents reported closing camps or canceling
      sessions. Most camps reported that they communicated with campers' families about
      pH1N1 and implemented control measures, including educating campers and staff
      about symptoms, isolating ill campers and staff, encouraging increased hand
      washing and hygiene practices and increasing the availability of hand sanitizers.
      Of the 43 camps with cases of ILI or laboratory-confirmed pH1N1, 25 (58%) used
      antiviral medication for treatment, and 18 (42%) used antiviral medications for
      prophylaxis; antiviral practices varied among camps. CONCLUSIONS: Summer camps in
      Maine were in general well prepared for pH1N1. Most camps followed public health
      guidance and implemented preventive measures. Many camps experienced ILI and
      outbreaks during the season, but did not report major disruptions. Camps should
      review their preparedness and disease control plans annually and public health
      authorities should keep guidance and recommendations simple and consistent.

PMID- 22414903
TI  - Commentary: pediatric antifungal drug development: lessons learned and
      recommendations for the future.

PMID- 22414904
TI  - Infectious etiologies of transient neutropenia in previously healthy children.
AB  - BACKGROUND: Healthy children presenting with neutropenia are often hospitalized
      and treated empirically with antibiotics without an evidence of infection. The
      objective of this study was to investigate the infectious causes of isolated
      transient neutropenia in otherwise previously healthy children. METHOD: A 2-year
      prospective study was conducted at a tertiary hospital in Kuwait. All previously
      healthy children (aged 1 month to 12 years) hospitalized with isolated
      neutropenia defined as absolute neutrophil count (ANC) <= 1.5 * 10/L were
      enrolled in the study. Investigations to identify the infectious causes included
      blood and urine culture for bacteria whereas for viruses, serology for Epstein
      Barr virus, cytomegalovirus, adenovirus, parvovirus and polymerase chain reaction
      for human herpes virus 6 and enterovirus were performed. RESULTS: Fifty-five
      children were enrolled during the study. Children less than 2 years of age
      constituted 73% of the sample. There were 2 peaks of presentation: March-May
      (33%) and September-November (38%). Associated features were congested throat
      (56%), runny nose (53%) and cervical lymphadenopathy (20%). The median ANC on
      admission was 0.6 * 10/L. Associated infections were documented in 55% of
      enrolled children and were as follows: human herpesvirus 6, 30%; enterovirus,
      23%; influenza A H1N1, 13%; parvovirus, 10%; Epstein-Barr virus, 10%; urinary
      tract infection, (Eshcherichia coli) 7%; and adenovirus, 7%. No serious bacterial
      infection was identified, and the mean time for recovery of the ANC was 16.7 +/-
      15 days. CONCLUSIONS: Neutropenia in previously healthy children in Kuwait is
      caused by demonstrable infections in 55% of cases. Majority of children will
      recover their ANC completely within 1 month without significant infectious
      complications.

PMID- 22414905
TI  - Trend of pneumonia incidence among children infected with HIV in the era of
      highly active antiretroviral therapy.
AB  - We performed a retrospective study using a cross-sectional design for each year
      from 1997 to 2008 to evaluate the trend in pneumonia rates among HIV-infected
      children in the highly active antiretroviral therapy (HAART) era in Spain. We
      found that rate of pneumonia decreased among HIV-Infected children in the highly
      active antiretroviral therapy era but still remained higher than in the general
      population. Non-AIDS-defining pneumonia remains a significant health problem for
      HIV-infected children.

PMID- 22414906
TI  - The impact of the H1N1 influenza pandemic on clinical presentations and viral
      epidemiology of acute respiratory infection in preschool children in Brazil.
AB  - We assessed the impact of the H1N1 influenza pandemic on acute respiratory
      infection in young children from low-income families in Brazil. Influenza
      (specifically H1N1) detection in acute respiratory infection quintupled during
      the pandemic and, during its peak, it was associated with 30% of all acute
      respiratory infection visits to the emergency department. H1N1 was also
      associated with increased risk of hospitalization and coinfection.

PMID- 22414907
TI  - Trough lopinavir concentrations in preterm HIV-infected infants.
AB  - Because of serious adverse effects, the Food and Drug Administration warns
      against using lopinavir in infants younger than 42 weeks postconception. However,
      there is an imperative for early treatment. We report on our use of LPV in 8
      premature HIV-infected infants. The median age at initiation was 27 days. Trough
      values guided dosing. Five infants needed doses above 300 mg/m. Although no
      adverse events were noted, lopinavir usage requires caution and careful
      monitoring.

PMID- 22414908
TI  - Cholesterol efflux assay.
AB  - Cholesterol content of cells must be maintained within the very tight limits, too
      much or too little cholesterol in a cell results in disruption of cellular
      membranes, apoptosis and necrosis. Cells can source cholesterol from
      intracellular synthesis and from plasma lipoproteins, both sources are sufficient
      to fully satisfy cells' requirements for cholesterol. The processes of
      cholesterol synthesis and uptake are tightly regulated and deficiencies of
      cholesterol are rare. Excessive cholesterol is more common problem. With the
      exception of hepatocytes and to some degree adrenocortical cells, cells are
      unable to degrade cholesterol. Cells have two options to reduce their cholesterol
      content: to convert cholesterol into cholesteryl esters, an option with limited
      capacity as overloading cells with cholesteryl esters is also toxic, and
      cholesterol efflux, an option with potentially unlimited capacity. Cholesterol
      efflux is a specific process that is regulated by a number of intracellular
      transporters, such as ATP binding cassette transporter proteins A1 (ABCA1) and G1
      (ABCG1) and scavenger receptor type B1. The natural acceptor of cholesterol in
      plasma is high density lipoprotein (HDL) and apolipoprotein A-I. The cholesterol
      efflux assay is designed to quantitate the rate of cholesterol efflux from
      cultured cells. It measures the capacity of cells to maintain cholesterol efflux
      and/or the capacity of plasma acceptors to accept cholesterol released from
      cells. The assay consists of the following steps. Step 1: labelling cellular
      cholesterol by adding labelled cholesterol to serum-containing medium and
      incubating with cells for 24-48 h. This step may be combined with loading of
      cells with cholesterol. Step 2: incubation of cells in serum-free medium to
      equilibrate labelled cholesterol among all intracellular cholesterol pools. This
      stage may be combined with activation of cellular cholesterol transporters. Step
      3: incubation of cells with extracellular acceptor and quantitation of movement
      of labelled cholesterol from cells to the acceptor. If cholesterol precursors
      were used to label newly synthesized cholesterol, a fourth step, purification of
      cholesterol, may be required. The assay delivers the following information: (i)
      how a particular treatment (a mutation, a knock-down, an overexpression or a
      treatment) affects the capacity of cell to efflux cholesterol and (ii) how the
      capacity of plasma acceptors to accept cholesterol is affected by a disease or a
      treatment. This method is often used in context of cardiovascular research,
      metabolic and neurodegenerative disorders, infectious and reproductive diseases.

PMID- 22414909
TI  - Oral ibuprofen for patent ductus arteriosus: effective and safe or just cheap?
      Commentary on R. Neumann et al.: Oral ibuprofen versus intravenous ibuprofen or
      intravenous indomethacin for the treatment of patent ductus arteriosus in preterm
      infants: a systematic review and meta-analysis (Neonatology 2012;102:9-15).

PMID- 22414910
TI  - Tumor metabolism as modulator of immune response and tumor progression.
AB  - About a century ago Otto Warburg observed that tumor cells exhibited increased
      glycolysis despite the presence of oxygen and stated this metabolic shift to
      glycolysis as the origin of cancer cell. In the meantime it has become clear,
      that the altered glucose metabolism is only one piece of the tumor metabolome
      puzzle. In addition, amino acid, lipid and adenosine metabolism are adapted to
      fulfill the tumors needs for energy and generation of building blocks such as
      lipids and nucleotides for new cell structures. The altered tumor metabolism
      leads to accumulation of specific metabolites in the tumor environment and
      creates a favorable milieu for tumor growth, progression and metastasis. These
      tumor-derived metabolites are important players in immune escape mechanisms
      beside other known factors such as cytokines, chemokines and growth factors. A
      variety of metabolites re-educate immune cells and prevent an effective immune
      response against tumor cells. Furthermore, tumor infiltrating immune cells
      support tumor growth by the secretion of cytokines, growth factors and other
      metabolic determinants. Hence, a complex interplay of tumor metabolites,
      cytokines and stromal factors is active in tumors and facilitates their
      establishment and growth. Pharmacological blockade of tumor metabolites could
      overcome some limitations of cancer treatment and rescue the endogenous immune
      response against tumor cells.

PMID- 22414912
TI  - Direction-tunable nanotwins in copper  nanowires by laser-assisted 
      electrochemical deposition.
AB  - Nanotwins can improve mechanical strength and maintain high electrical
      conductivity in metallic nanowires. We demonstrated a method of pulsed-laser
      assisted electrodeposition, which could form dense nanotwins with tunable
      directions in copper nanowires of uniform sizes. Transmission electron microscopy
      characterization showed with a growth potential of -0:2 V, nanotwins tend to
      align along the longitudinal direction of the nanowires, whereas at a larger
      potential of -0:8 V, nanotwins of {111}g/<112> type perpendicular to the
      longitudinal direction of the wire were formed. The two types of nanotwins were
      investigated by comparing the microstructures under different electrochemical
      conditions and laser irradiation energies. Two different mechanisms are proposed
      annealing twins and growth twins.

PMID- 22414911
TI  - Tumor associated regulatory dendritic cells.
AB  - Immune effector and regulatory cells in the tumor microenvironment are key
      factors in tumor development and progression as the pathogenesis of cancer
      vitally depends on the multifaceted interactions between various
      microenvironmental stimuli provided by tumor-associated immune cells. Immune
      regulatory cells participate in all stages of cancer development from the
      induction of genomic instability to the maintenance of intratumoral angiogenesis,
      proliferation and spreading of malignant cells, and formation of premetastatic
      niches in distal tissues. Dendritic cells in the tumor microenvironment serve as
      a double-edged sword and, in addition to initiating potent anti-tumor immune
      responses, may mediate genomic damage, support neovascularization, block anti
      tumor immunity and stimulate cancerous cell growth and spreading. Regulatory
      dendritic cells in cancer may directly and indirectly maintain antigen-specific
      and non-specific T cell unresponsiveness by controlling T cell polarization, MDSC
      and Treg differentiation and activity, and affecting specific microenvironmental
      conditions in premalignant niches. Understanding the mechanisms involved in
      regulatory dendritic cell polarization and operation and revealing
      pharmacological means for harnessing these pathways will provide additional
      opportunities for modifying the tumor microenvironment and improving the efficacy
      of different therapeutic approaches to cancer.

PMID- 22414913
TI  - Nonsynonymous variants in mt-Nd2, mt-Nd4, and mt-Nd5 are linked to effects on
      oxidative phosphorylation and insulin sensitivity in rat conplastic strains.
AB  - Common inbred strains of the laboratory rat can be divided into four different
      mitochondrial DNA haplotype groups represented by the SHR, BN, LEW, and F344
      strains. In the current study, we investigated the metabolic and hemodynamic
      effects of the SHR vs. LEW mitochondrial genomes by comparing the SHR to a new
      SHR conplastic strain, SHR-mt(LEW); these strains are genetically identical
      except for their mitochondrial genomes. Complete mitochondrial DNA (mtDNA)
      sequence analysis comparing the SHR and LEW strains revealed gene variants
      encoding amino acid substitutions limited to a single mitochondrial enzyme
      complex, NADH dehydrogenase (complex I), affecting subunits 2, 4, and 5. Two of
      the variants in the mt-Nd4 subunit gene are located close to variants known to be
      associated with exercise intolerance and diabetes mellitus in humans. No variants
      were found in tRNA or rRNA genes. These variants in mt-Nd2, mt-Nd4, and mt-Nd5 in
      the SHR-mt(LEW) conplastic strain were linked to reductions in oxidative and
      nonoxidative glucose metabolism in skeletal muscle. In addition, SHR-mt(LEW)
      conplastic rats showed increased serum nonesterified fatty acid levels and
      resistance to insulin stimulated incorporation of glucose into adipose tissue
      lipids. These results provide evidence that inherited variation in mitochondrial
      genes encoding respiratory chain complex I subunits, in the absence of variation
      in the nuclear genome and other confounding factors, can influence glucose and
      lipid metabolism when expressed on the nuclear genetic background of the SHR
      strain.

PMID- 22414914
TI  - Effect of the metabolic environment at key stages of follicle development in
      cattle: focus on steroid biosynthesis.
AB  - Cellular mechanisms that contribute to low estradiol concentrations produced by
      the preovulatory ovarian follicle in cattle with a compromised metabolic status
      are largely unknown. To gain insight into the main metabolic mechanisms affecting
      preovulatory follicle function, two different animal models were used. Experiment
      1 compared Holstein-Friesian nonlactating heifers (n = 17) and lactating cows (n
      = 16) at three stages of preovulatory follicle development: 1) newly selected
      dominant follicle in the luteal phase (Selection), 2) follicular phase before the
      LH surge (Differentiation), and 3) preovulatory phase after the LH surge
      (Luteinization). Experiment 2 compared newly selected dominant follicles in the
      luteal phase in beef heifers fed a diet of 1.2 times maintenance (M, n = 8) or
      0.4 M (n = 11). Lactating cows and 0.4 M beef heifers had higher concentrations
      of beta-hydroxybutyrate, and lower concentrations of glucose, insulin, and IGF-I
      compared with dairy heifers and 1.2 M beef heifers, respectively. In lactating
      cows this altered metabolic environment was associated with reduced dominant
      follicle estradiol and progesterone synthesis during Differentiation and
      Luteinization, respectively, and in 0.4 M beef heifers with reduced dominant
      follicle estradiol synthesis. Using a combination of RNA sequencing, Ingenuity
      Pathway Analysis, and qRT-PCR validation, we identified several important
      molecular markers involved in steroid biosynthesis, such as the expression of
      steroidogenic acute regulatory protein (STAR) within developing dominant
      follicles, to be downregulated by the catabolic state. Based on this, we propose
      that the adverse metabolic environment caused by lactation or nutritional
      restriction decreases preovulatory follicle function mainly by affecting
      cholesterol transport into the mitochondria to initiate steroidogenesis.

PMID- 22414915
TI  - In pursuit of scientific excellence: sex matters.

PMID- 22414916
TI  - Genetic support and diversity of acquired extended-spectrum beta-lactamases in
      Gram-negative rods.
AB  - Genes encoding extended-spectrum beta-lactamases (ESBLs) have been reported in a
      variety of Gram-negative species, mostly in Enterobacteriaceae, Pseudomonas
      aeruginosa and Acinetobacter baumannii. They are either TEM- or SHV-derivatives,
      CTX-M-like enzymes and less frequently of the GES, PER, or VEB types. The
      mechanisms at the origin of their acquisition are diverse, and mostly are related
      to insertion sequences, transposons and class 1 integrons. This diversity of
      genetic vehicles at the origin of these mobilization/acquisition processes may
      explain spread of ESBLs worldwide.

PMID- 22414917
TI  - Evidence of purifying selection on merozoite surface protein 8 (MSP8) and 10
      (MSP10) in Plasmodium spp.
AB  - Evidence for natural selection, positive or negative, on gene encoding antigens
      may indicate variation or functional constraints that are immunologically
      relevant. Most malaria surface antigens with high genetic diversity have been
      reported to be under positive-diversifying selection. However, antigens with
      limited genetic variation are usually ignored in terms of the role that natural
      selection may have in generating such patterns. We investigated orthologous genes
      encoding two merozoite proteins, MSP8 and MSP10, among several mammalian
      Plasmodium spp. These antigens, together with MSP1, are among the few MSPs that
      have two epidermal growth factor-like domains (EGF) at the C-terminal. Those EGF
      are relatively conserved (low levels of genetic polymorphism) and have been
      proposed to act as ligands during the invasion of RBCs. We use several
      evolutionary genetic methods to detect patterns consistent with natural selection
      acting on MSP8 and MSP10 orthologs in the human parasites Plasmodium falciparum
      and P. vivax, as well as closely related malarial species found in non-human
      primates (NHPs). Overall, these antigens have low polymorphism in the human
      parasites in comparison with the orthologs from other Plasmodium spp. We found
      that the MSP10 gene polymorphism in P. falciparum only harbor non-synonymous
      substitutions, a pattern consistent with a gene under positive selection.
      Evidence of purifying selection was found on the polymorphism observed in both
      orthologs from P. cynomolgi, a non-human primate parasite closely related to P.
      vivax, but it was not conclusive in the human parasite. Yet, using phylogenetic
      base approaches, we found evidence for purifying selection on both MSP8 and MSP10
      in the lineage leading to P. vivax. Such antigens evolving under strong
      functional constraints could become valuable vaccine candidates. We discuss how
      comparative approaches could allow detecting patterns consistent with negative
      selection even when there is low polymorphism in the extant populations.

PMID- 22414918
TI  - Phylogenetic analysis supports horizontal gene transfer of L-amino acid oxidase
      gene in Streptococcus oligofermentans.
AB  - Phylogenetic analysis of 10 amino acid sequences from 19 Streptococcus species
      showed that S. oligofermentans clustered within the mitis group. However, the l
      amino acid oxidase (LAAO) of S. oligofermentans showed a different clustering
      pattern from the other proteins analyzed implicating horizontal gene transfer
      (HGT) in the origin of the S. oligofermentans LAAO gene. LAAO of S.
      oligofermentans is known to confer ability to compete with other oral cavity
      bacteria, most notably S. mutans; therefore, the HGT event may have been
      important in extending the ecological niche occupied by this species, consistent
      with those of other studies suggesting that HGT can play a key role in enabling
      bacterial species to occupy new ecological niches.

PMID- 22414919
TI  - Impact of psychotropic drugs on adult hippocampal neurogenesis.
AB  - This review focuses on the relationship between psychotropic drugs and adult
      hippocampal neurogenesis. Adult neurogenesis is important for learning and
      memory, as well as for depression and anxiety. There is some evidence that
      chronic treatment with opiates, stimulants and entactogens decreases neurogenesis
      and consequently impairs cognitive function, as well as inducing depressive-like
      behaviour in animals during drug withdrawal. On the other hand, NMDA receptor
      antagonists increase neurogenesis, but negatively affect cognitive function and
      have an antidepressant-like profile. We suggest that drug-induced changes in
      neurogenesis have a greater and more concise effect on emotive state reflecting
      the direction of influencing new cells proliferation than the performance of
      cognitive tasks. In this review we provide some evidence for this assumption.

PMID- 22414920
TI  - Alcohol misuse Y91 coding in ICD-11: rational terminology and logical coding
      specifically to encourage early identification and advice.
AB  - Alcohol misuse is a common presentation to the Emergency Department (ED). The
      International Classification of Diseases ICD-10 for alcohol misuse, both under
      F10 and Y90/Y91, is not straightforward. The practicalities of coding ED
      attendances reveal an increasing detachment from ICD-10 (currently under review).
      Early identification [sometimes using blood alcohol concentrations (BACs)] and
      brief advice (IBA) can reduce unscheduled alcohol-related ED re-attendance. The
      UK Government Department of Health has implemented use of the terms 'Hazardous
      Drinking', 'Harmful Drinking' and 'Dependent Drinking' in its Public Service
      Agreements aimed at reducing harm by alcohol. Simplifying coding might increase
      IBA usage. We suggest that coding improvements in ICD-11 should update Y91
      (currently 'clinical assessment')-with ICD-10 Y90 remaining for BAC to classify a
      patient's 'alcohol status'. Y90 and Y91 together would indicate the urgency for
      early IBA and/or speciality referral, aiming to reduce the prevalence of
      'Dependent Drinking'.

PMID- 22414921
TI  - The effects of prenatal alcohol exposure on the developmental retina of mice.
AB  - AIMS: Our aim is to investigate the effects of prenatal alcohol exposure (PAE) on
      the development of retinal bipolar and horizontal cells. METHODS: The alterations
      of the retinal bipolar and horizontal cells in P7, P14 and P30 mice were observed
      after PAE, with immunofluorescent labeling and DiI diolistic assay. RESULTS: The
      retinal development of filial pups was affected by PAE in a dose-dependent and
      long-term manner. The number of bipolar cells of alcohol groups was significantly
      lower than that of the control, and the dendritic receptive field of horizontal
      cells was also significantly smaller than those of the control groups (P < 0.01).
      CONCLUSION: PAE was able to cause retarded development of pup retinal neural
      cells.

PMID- 22414922
TI  - CAGE, RAPS4, RAPS4-QF and AUDIT screening tests for men and women admitted for
      acute alcohol intoxication to an emergency department: are standard thresholds
      appropriate?
AB  - AIMS: A number of screening instruments are routinely used in Emergency
      Department (ED) situations to identify alcohol-use disorders (AUD). We wished to
      study the psychometric features, particularly concerning optimal thresholds
      scores (TSs), of four assessment scales frequently used to screen for abuse
      and/or dependence, the cut-down annoyed guilty eye-opener (CAGE), Rapid Alcohol
      Problem Screen 4 (RAPS4), RAPS4-quantity-frequency and AUD Identification Test
      (AUDIT) questionnaires, particularly in the sub-group of people admitted for
      acute alcohol intoxication (AAI). METHODS: All included patients [AAI admitted to
      ED (blood alcohol level >=0.8 g/l)] were assessed by the four scales, and with a
      gold standard (alcohol dependence/abuse section of the Mini International
      Neuropsychiatric Interview), to determine AUD status. To investigate the TSs of
      the scales, we used Youden's index, efficiency, receiver operating characteristic
      (ROC) curve techniques and quality ROC curve technique for optimized TS (indices
      of quality). RESULTS: A total of 164 persons (122 males, 42 females) were
      included in the study. Nineteen (11.60%) were identified as alcohol abusers alone
      and 128 (78.1%) as alcohol dependents (DSM-IV). Results suggest a statistically
      significant difference between men and women (P < 0.05) in performance of the
      screening tests RAPS4 (>=1) and CAGE (>=2) for detecting abuse. Also, in this
      population, we show an increase in TSs of RAPS4 (>=2) and CAGE (>=3) for
      detecting dependence compared with those typically accepted in non-intoxicated
      individuals. The AUDIT test demonstrates good performance for detecting alcohol
      abuse and/or alcohol-dependent patients (>=7 for women and >=12 for men) and for
      distinguishing alcohol dependence (>=11 for women and >=14 for men) from other
      conditions. CONCLUSION: Our study underscores for the first time the need to
      adapt, taking into account gender, the thresholds of tests typically used for
      detection of abuse and dependence in this population.

PMID- 22414925
TI  - Microbubble incision as a new rescue technique for big-bubble deep anterior
      lamellar keratoplasty with failed bubble formation.
AB  - PURPOSE: To describe a new surgical technique allowing dissection down to
      Descemet membrane in big-bubble deep anterior lamellar keratoplasty (DALK) with
      failed big-bubble formation (the "microbubble incision technique"). METHODS: This
      is an interventional case series of 10 consecutive patients with keratoconus
      undergoing intended big-bubble DALK with failure to establish a normal big
      bubble. In all patients, repeated air injections into the stroma were performed,
      leaving a whitish colored stroma. Lamellar dissection as far down as possible was
      then performed within this white tissue. As soon as the anterior chamber was
      visible, a large remaining intrastromal air bubble was incised with a sharp 15
      degree knife introduced perpendicular to the tissue to open up this predescemetic
      bubble. If deeper air bubbles were still visible, this approach was repeated.
      Using a blunt spatula, this new layer was then prepared and viscodissection
      performed. RESULTS: Using this novel approach, in 9 of the 10 patients, it was
      possible to dissect down to Descemet membrane. Macroperforation made conversion
      to penetrating keratoplasty necessary in 1 patient. Microperforations not
      necessitating conversion occurred in 2 patients. All 9 patients with "rescued"
      DALK had an uneventful postoperative course and had a mean visual acuity of 20/63
      +/- 20/125 (range, 20/500-20/50) and a mean endothelial cell count of 1672 +/-
      163 cells per square millimeter (range, 1493-1867 cells/mm) at 3 months.
      CONCLUSIONS: Microbubble incision is a new rescue technique for big-bubble DALK
      patients without bubble formation allowing for a safer dissection down to
      Descemet membrane.

PMID- 22414926
TI  - Head circumference in untreated and IGF-I treated patients with Laron syndrome:
      comparison with untreated and hGH-treated children with isolated growth hormone
      deficiency.
AB  - BACKGROUND: Head circumference (HC) is a simple and practical measure of brain
      size, development and longitudinal measurements of the HC in childhood are an
      index of brain growth. OBJECTIVE: To determine the effects of long IGF-I
      deficiency and treatment on HC in patients with Laron syndrome (LS). PATIENTS: 20
      untreated adult LS patients, aged 48.4+/-11.2 years and 13 LS patients treated
      between ages of 5.6+/-4 to 11.3+/-3 years were studied. 15 patients with
      congenital IGHD treated between age 6.1+/-4 and 13+/-4 by hGH served as controls.
      METHODS: HC was expressed as standard deviation (SD) and Ht as SDS. HC was
      measured and plotted on Nellhaus charts. Linear height (Ht) was measured by a
      Harpenden Stadiometer. CONCLUSIONS: The mean HC deficit of the adult untreated LS
      males was -2.9+/-0.6 SD compared to a Ht deficit of -7.0+/-1.7 SDS. The HC of the
      LS adult females was -3.6+/-1 SD compared to a Ht SDS of -6.9+/-1.5 (p<0.001).
      IGF-I treatment (150-200 MUg/kg once daily) increased the HC from -3.3+/-0.9 (m+/
      SD) to normal values (0.87+/-1.8 SD) (p<0.001) in 11/13 children. The Ht SDS
      deficit decreased only by 1.5 SDS. hGH treatment of cIGHD children increased the
      HC from -2.0+/-1.8 to 0.3+/-1.2 SD and the Ht SDS from -4.8+/-1.6 to 1.6+/-1.0.

PMID- 22414923
TI  - Stress-induced impairments in prefrontal-mediated behaviors and the role of the N
      methyl-D-aspartate receptor.
AB  - The prefrontal cortex (PFC) mediates higher-order cognitive and executive
      functions that subserve various complex, adaptable behaviors, such as cognitive
      flexibility, attention, and working memory. Deficits in these functions typify
      multiple neuropsychiatric disorders that are caused or exacerbated by exposure to
      psychological stress. Here we review recent evidence examining the effects of
      stress on executive and cognitive functions in rodents and discuss an emerging
      body of evidence that implicates the N-methyl-D-aspartate receptor (NMDAR) as a
      potentially critical molecular mechanism mediating these effects. Future work in
      this area could open up new avenues for developing pharmacotherapies for
      ameliorating cognitive dysfunction in neuropsychiatric disease.

PMID- 22414927
TI  - Impact of race on predialysis discussions and kidney transplant preemptive wait
      listing.
AB  - BACKGROUND/AIMS: US registry data have consistently shown that blacks are less
      likely than whites to be wait-listed before beginning dialysis. METHODS: The
      Comprehensive Dialysis Study (CDS) was a special study conducted by the US Renal
      Data System (USRDS) in which a national cohort of patients who began maintenance
      dialysis therapy in 2005-2007 were asked whether kidney transplantation (KT) had
      been discussed with them before they started dialysis. Using responses from black
      and white CDS participants and information from the USRDS, we investigated
      preemptive wait-listing as a function of patient-reported predialysis KT
      discussion. RESULTS: Among those reporting early KT discussion, 31.0% of patients
      preemptively wait-listed were black, compared to 27.5% of those not preemptively
      wait-listed. Two thirds of preemptively wait-listed patients had received
      nephrology care more than 12 months before starting dialysis and reported that KT
      was discussed with them 12 months or more before dialysis. Early KT discussion
      and higher serum albumin and hemoglobin levels remained significant predictors of
      preemptive wait-listing in an adjusted logistic regression analysis. Among those
      preemptively wait-listed, 33% of blacks and 60% of whites had received a
      transplant by September 30, 2009 (study end date). CONCLUSION: Early KT
      discussion appeared to reduce barriers to black patients' waiting list placement
      before the start of dialysis, which in turn may facilitate earlier access to a
      deceased donor organ transplant.

PMID- 22414928
TI  - Testosterone-induced prostate growth is blocked by co- and preadministration of
      norethisterone enanthate in castrated cynomolgus monkeys.
AB  - INTRODUCTION: Prostate size and function are regulated by testosterone. However,
      the progesterone receptor is expressed in the primate prostate. Progestins affect
      the prostate by endocrine suppression, but can also act directly. Examining the
      role of progestins, we studied the effects of norethisterone (NET) on
      testosterone undecanoate (TU)-induced prostate growth in castrated macaques.
      MATERIALS AND METHODS: Two groups (n = 6 for each group) received TU every 9
      weeks. Using a crossover setting, group I received norethisterone enanthate
      (NETE) 3 times at 3-week intervals, while group II received placebo. After 9
      weeks, placebo was administered to group I, and group II received NETE. RESULTS:
      In group II, the prostate grew under TU and placebo over the first period. In
      group I, coadministered with NETE, the increase was lower. After the crossover,
      prostates of animals previously treated with NETE did not increase to normal
      values under placebo. Prostates of animals treated with TU and placebo in the
      first period shrank following NETE administration after the crossover. The long
      half-life of NET can explain the lack of a TU effect on animals coadministered
      with NETE after the crossover. CONCLUSIONS: Pre- and coadministration of NET
      reduces testosterone-induced prostate growth with possible implications for the
      treatment of benign prostate hyperplasia and hormonal male contraception.

PMID- 22414929
TI  - Ternary compound CuInTe2: a promising thermoelectric material with diamond-like
      structure.
AB  - We report a ternary compound CuInTe(2) with diamond-like structure as a promising
      thermoelectric material in moderate temperature range. Due to the good electrical
      properties and low thermal conductivity, the zT value of CuInTe(2) reaches 1.18
      at 850 K, better than any other un-doped diamond-like material.

PMID- 22414930
TI  - Microbiological quality of cuttlefish (Sepia pharaonis) fillets stored in dry and
      wet ice.
AB  - Microbiological quality of cuttlefish (Sepia pharaonis) fillets stored in three
      different ice conditions was studied. Fillets stored in wet ice at a ratio of 1:1
      (package III) were sensorially acceptable for only 18 h, while that stored in dry
      ice at 1:1 (package I) and combination of dry ice and wet ice at 1:0.2:0.5
      (package II) were in acceptable condition up to 24 h without re-icing and thus
      there was an extension of shelf life by about 33%. Total bacterial load was 7
      log10 cfu/g at the end of the storage period. Total psychrophilic population
      increased from zero to 7 log10 cfu/g while total lactic acid bacteria from zero
      to 5 log10 cfu/g. H2S producers were detected only at 18 h, with a count of 1
      log10 cfu/g. Sulphite-reducing Clostridia increased gradually from zero to 110
      most probable number count/g. Fresh cuttlefish fillets carried a bacterial flora
      of Micrococcus, Planococcus, Streptococcus, Moraxella, Proteus and Aeromonas.
      Pseudomonas was dominant in wet ice pack, while Aeromonas was dominant in both
      the dry ice and combination pack. Immediately after packing, the temperatures
      recorded in packages I, II and III were 10.5, 1.2 and 3.0  degrees C,
      respectively, which drastically decreased in 1 h and then maintained and finally
      increased gradually. The results indicate that use of combination of dry ice and
      wet ice is economical and very much useful to seafood industries, as this package
      considerably reduced the cost of air freight, as well as improved the quality and
      shelf life of cuttlefish.

PMID- 22414931
TI  - Correlation of average hydrophobicity, water/air interface surface rheological
      properties and foaming properties of proteins.
AB  - A comparative study on the behavior in the air-water interface of beta
      lactoglobulin, alpha-lactoalbumin, glycinin and beta-conglycinin was performed.
      The behavior at the interface was evaluated by equilibrium surface tension and
      surface rheological properties of adsorbed films. There were significant
      differences (alpha <= 0.05) in the values of the constants of adsorption to the
      interface of the four proteins. The glycinin had the slowest rate of adsorption,
      due to its low average hydrophobicity, low molecular flexibility and large
      molecular size. Smaller proteins like beta-lactoglobulin and alpha-lactoalbumin
      tended to greater equilibrium pressure values than the larger proteins because of
      its higher rate of adsorption to the interface. The foam capacity of proteins
      showed a positive correlation with the average hydrophobicity; the maximal
      retained liquid volume or the initial rate of passage of liquid to foam were
      significantly lower (alpha <= 0.05) when protein was glycinin. The dilatational
      modulus of glycinin was the lowest, which implies lowest resistance to disruption
      of the film. Glycinin protein has lower proportion of gravitational drainage and
      higher disproportionation having perhaps a less resistant film. In conclusion,
      beta-conglycinin and whey proteins showed a similar behavior, so beta-conglycinin
      might be the best soybean protein to replace milk proteins in food formulations.

PMID- 22414932
TI  - Potential of Spanish sour-sweet pomegranates (cultivar C25) for the juice
      industry.
AB  - Commercial juices of sweet pomegranates and fresh juices of sour-sweet
      pomegranates were analysed for organic acids, sugars, antioxidant activity,
      volatile composition, sensory profile and consumer liking. Organic acids and
      sugars were analysed by high-performance liquid chromatography, while volatiles
      were extracted using hydrodistillation and analysed by gas chromatography-mass
      spectrometry and gas chromatography-flame ionisation detector. Malic acid was
      predominant in sweet juices while citric acid in sour-sweet samples. Fructose and
      glucose were found as the predominant sugars in all juices. A total of 18
      compounds were found in pomegranate aroma profile, including monoterpenes,
      aldehydes, alcohols, monoterpenoids and linear hydrocarbons; the most abundant
      compounds were 3-carene, alpha-terpinene and alpha-terpineol. The total
      concentration of volatiles ranged from 2.0 up to 5.1 mg/L, with commercial
      samples presenting higher total concentrations due to the presence of peel
      volatiles. The high potential of sour-sweet pomegranate fruits for the juice
      industry was supported by (a) the high values of positive attributes, such as
      colour and fresh pomegranate flavour and (b) the high overall liking of
      consumers.

PMID- 22414933
TI  - Phenolic compounds and sensorial characterization of wines aged with alternative
      to barrel products made of Spanish oak wood (Quercus pyrenaica Willd.).
AB  - Wood of Quercus pyrenaica has suitable properties for the wine ageing process.
      However, the forest available for the barrel making from this particular type of
      tree is very limited. Nevertheless, it is highly advisable to use this kind of
      wood in order to manufacture alternative oak products. This study presents the
      results of ageing the same red wine using different pieces of wood (chips and
      staves) of Spanish oak (Q. pyrenaica), American oak (Quercus alba) and French oak
      (Quercus petraea) in conjunction with small, controlled amounts of oxygen. In
      addition, the phenolic parameters, colour and sensory analysis point out that
      wines aged with Q. pyrenaica pieces have similar enological characteristics to
      those aged with American or French oak pieces of wood (chips and staves).
      Furthermore, the total oxygen consumed and its relation with sensory properties
      also has been studied in this article in order to know how the oxygen behaves in
      these processes. Besides, it is going to put forward the fact that chips and
      staves from Q. pyrenaica oak are suitable for the ageing of red wines and better
      considered than American or French ones, showing higher aromatic intensity,
      complexity, woody, balsamic and cocoa. Finally, the tasters valued highly the
      wines with staves, pointing out its flavour and roundness in mouth.

PMID- 22414934
TI  - The antimicrobial effects of cranberry against Staphylococcus aureus.
AB  - The antimicrobial effects of the American cranberry (Vaccinium macrocarpon) on a
      major food-borne pathogen, Staphylococcus aureus, were investigated using
      commercially obtained Lakewood(r) organic cranberry juice and Ocean Spray(r)
      cranberry juice cocktail and four other berry fruit extracts (acai berry,
      strawberry, raspberry, and blueberry). The results showed that cranberry is a
      potent antimicrobial against S. aureus and the most potent among the berries
      studied. The order of percentage inhibition of bacterial growth at the same
      concentration of phenolic materials as gallic acid equivalents was Lakewood
      cranberry juice > Ocean Spray cranberry juice ? blueberry > acai berry ?
      raspberry ? strawberry. The antimicrobial effect was not due to the acidity of
      the berries as NaOH-neutralized samples were almost as effective in terms of
      percentage inhibition of viable cell growth. Solid-phase extraction of cranberry
      juice using C18 solid phase showed that the antimicrobial effects reside
      exclusively with the C18-bound materials.

PMID- 22414935
TI  - Preventing the wound-induced deterioration of Yali pears by chitosan coating
      treatments.
AB  - Yali pears (Pyrus bretschneideri Rehd.) are susceptible to mechanical damage. In
      this study, the protective effects of chitosan treatments on the quality of
      bruised pears were evaluated. The fruit were treated with 1.5% chitosan before or
      after bruise damage, respectively. Then, the fruit were stored at 16  degrees C
      and 85-90% relative humidity. Postharvest quality parameters were analyzed during
      the storage. Bruise damage accelerated the decrease of firmness and the ratio of
      sugar to acid, while a delay of firmness and sugar-to-acid ratio in those pears
      treated with chitosan before or after was found. Meanwhile, chitosan treatments
      both before and after damage delayed the color changes caused by damage,
      inhibited disease incidence increase, and enhanced the bruise recovery during the
      storage. Our results suggested that chitosan treatment could be used to control
      the physiological responses induced by bruise damage.

PMID- 22414936
TI  - The influence of inoculum composition on selected bioactive and nutritional
      parameters of grass pea tempeh obtained by mixed-culture fermentation with
      Rhizopus oligosporus and Aspergillus oryzae strains.
AB  - Tempeh is a popular Indonesian product obtained from legume seeds by solid-state
      fermentation with Rhizopus sp. The aim of this research was to study the effect
      of simultaneous mixed-culture fermentation of grass pea seeds on selected
      parameters of products as compared to traditional tempeh. The inoculum contained
      different ratios of Rhizopus oligosporus and Aspergillus oryzae spores. The
      simultaneous fermentation of grass pea seeds with inoculum consisting of 1.2 *
      10(6) R. oligosporus and 0.6 * 10(6) A. oryzae spores (per 60 g of seeds)
      resulted in a product of improved quality, as compared with traditionally made
      tempeh (obtained after inoculation with 1.2 * 10(6) R. oligosporus spores), at
      the same fermentation time. This product had radical scavenging ability 70%
      higher than the one obtained with pure R. oligosporus culture and contained 2.23
      g/kg dm of soluble phenols. The thiamin and riboflavin levels were above three
      (340 ug/g dm) and two (50.50 ug/g dm) folds higher than in traditionally made
      tempeh, respectively. The product had 65% in vitro bioavailability of proteins
      and 33% in vitro bioavailability of sugars. It also contained 40% less 3-N-oxalyl
      L-2, 3-diaminopropionic acid (0.074 g/kg dm), as compared to traditional tempeh.

PMID- 22414938
TI  - Left ventricular systolic and diastolic function in obstructive sleep apnea:
      impact of continuous positive airway pressure therapy.
AB  - BACKGROUND: Previous studies in obstructive sleep apnea (OSA) were limited by
      study cohorts with comorbidities that confound assessment of left ventricular
      (LV) systolic and diastolic function. We comprehensively evaluated LV function
      using 2-dimensional echocardiography (2DE), tissue Doppler imaging (TDI), and 3
      dimensional echocardiography (3DE) in subjects moderate-severe OSA, who were
      compared with disease (patients with hypertension, no OSA) and healthy control
      subjects. METHODS AND RESULTS: A total of 120 subjects (n=40 each of matched OSA,
      hypertension and healthy cohorts) underwent echocardiographic examination for the
      assessment of septal and posterior wall thickness, LV mass index, LV volumes and
      ejection fraction, mitral valve inflow indices (E, A), mitral annular velocity
      (S, E'), and left atrial volume index (LAVI). OSA subjects were treated with
      continuous positive airway pressure (mean duration of 26 weeks), after which the
      echocardiographic parameters were reassessed. Posterior wall thickness and LV
      mass index were significantly higher in OSA and hypertensive groups compared with
      healthy. Systolic S velocity was reduced in OSA and hypertensive compared with
      healthy control subjects (P<0.05). Diastolic function (E/A, IVRT, and E/E') was
      impaired in both OSA and hypertensive groups. On 3DE, mean LAVI was significantly
      greater in OSA and hypertensive compared with healthy. In OSA patients,
      continuous positive airway pressure therapy resulted in reduction of the
      posterior wall thickness (P=0.02) and improvement in LV ejection fraction
      (P<0.05), systolic S velocity (P<0.05), and diastolic LV impairment parameters.
      CONCLUSIONS: Moderate to severe OSA causes structural and functional changes in V
      function and are comparable to that seen in hypertension. These abnormalities
      significantly improve after CPAP therapy.

PMID- 22414937
TI  - Neural correlates of attention bias to threat in post-traumatic stress disorder.
AB  - Attentional biases have been proposed to contribute to symptom maintenance in
      posttraumatic stress disorder (PTSD), although the neural correlates of these
      processes have not been well defined; this was the goal of the present study. We
      administered an attention bias task, the dot probe, to a sample of 37 (19
      control, 18 PTSD+) traumatized African-American adults during fMRI. Compared to
      controls, PTSD+ participants demonstrated increased activation in the
      dorsolateral prefrontal cortex (dlPFC) in response to threat cue trials. In
      addition, attentional avoidance of threat corresponded with increased
      ventrolateral prefrontal cortex (vlPFC) and dorsal anterior cingulate cortex
      (dACC) activation in the PTSD group, a pattern that was not observed in controls.
      These data provide evidence to suggest that relative increases in dlPFC, dACC and
      vlPFC activation represent neural markers of attentional bias for threat in
      individuals with PTSD, reflecting selective disruptions in attentional control
      and emotion processing networks in this disorder.

PMID- 22414939
TI  - Care and outcomes of Hispanic patients admitted with heart failure with preserved
      or reduced ejection fraction: findings from get with the guidelines-heart
      failure.
AB  - BACKGROUND: Although individuals of Hispanic ethnicity are at high risk for
      developing heart failure (HF), little is known about differences between Hispanic
      HF patients stratified by left ventricular ejection fraction (EF). We compared
      characteristics, quality of care, and outcomes between Hispanic and non-Hispanic
      white patients hospitalized for HF with preserved EF (PEF) or reduced EF (REF).
      METHODS AND RESULTS: From 247 hospitals in Get With The Guidelines-Heart Failure
      between 2005-2010, 6117 Hispanics were compared with 71 859 non-Hispanic whites.
      Forty-six percent of Hispanics had PEF (EF >40%), whereas 54% had REF (EF <40%);
      55% and 45% of non-Hispanic whites had PEF and REF, respectively. Relative to non
      Hispanic whites, Hispanics with PEF or REF were more likely to be younger and to
      have diabetes, hypertension, and overweight/obesity. In multivariate analysis, a
      lower mortality risk was observed among Hispanics with PEF (odds ratio, 0.50; 95%
      confidence interval, 0.31-0.81; P=0.005) but not in Hispanics with REF (odds
      ratio, 0.94; 95% confidence interval, 0.62-1.43; P=0.784) compared with non
      Hispanic whites. In all groups, composite performance improved within the study
      period (Hispanics PEF: 75.2-95.1%; non-Hispanic whites PEF: 79.0-92.7%; Hispanics
      REF: 67.7-88.4%; non-Hispanic whites REF: 60.8-85.6%, P<0.0001). CONCLUSIONS:
      Hispanic HF patients with PEF had better in-hospital survival than non-Hispanic
      whites with PEF. Inpatient mortality was similar between groups with REF. Quality
      of care was similar and improved over time irrespective of ethnicity,
      highlighting the potential benefit of performance improvement programs in
      promoting equitable care.

PMID- 22414940
TI  - A diruthenium soft ferromagnet showing T(c) = 3.0 K:
      Mn4(H2O)16H[Ru2(CO3)4]2[Ru2(CO3)4(H2O)2].11H2O.
AB  - A three-dimensional CO(3)(2-)-bridged Mn(II)-Ru(2)(II,III) complex,
      Mn(4)(H(2)O)(16)H[Ru(2)(CO(3))(4)](2)[Ru(2)(CO(3))(4)(H(2)O)(2)].11H(2)O (1), was
      synthesized by self-assembling Ru(2)(CO(3))(4)(3-) paddle-wheel precursors and
      Mn(2+) cations. It contains an unprecedented layer [Ru(2)(CO(3))(4)](n)(3n-) with
      (4,4) network. The ferromagnetic coupling between spin centers results in
      ordering below 3.0 K.

PMID- 22414948
TI  - Sensory systems: sounds like competition.

PMID- 22414949
TI  - Synaptic transmission: X marks the exocytotic spot (and foretells vesicle fusion
      mode).

PMID- 22414944
TI  - Obesity and the brain: how convincing is the addiction model?
AB  - An increasingly influential perspective conceptualizes both obesity and
      overeating as a food addiction accompanied by corresponding brain changes.
      Because there are far-reaching implications for clinical practice and social
      policy if it becomes widely accepted, a critical evaluation of this model is
      important. We examine the current evidence for the link between addiction and
      obesity, identifying several fundamental shortcomings in the model, as well as
      weaknesses and inconsistencies in the empirical support for it from human
      neuroscientific research.

PMID- 22414952
TI  - Solvated electrons at the water-air interface: surface versus bulk signal in low
      kinetic energy photoelectron spectroscopy.
AB  - Time-resolved photoelectron spectroscopy at low kinetic energies (?5 eV) is
      applied to dilute iodide solutions with different surface and bulk contributions.
      The results indicate a pronounced surface sensitivity. Signals assigned to
      solvated electrons near the liquid surface decay rapidly on a sub-ps timescale.
      In contrast to the literature, a long-lived surface solvated electron at 1.6 eV
      binding energy is not observed.

PMID- 22414953
TI  - Exploring carrier transport phenomena  in a CVD-assembled graphene FET on 
      hexagonal boron nitride.
AB  - The supporting substrate plays a crucial role in preserving the superb electrical
      characteristicsof an atomically thin 2D carbon system. We explore carrier
      transport behavior in achemical-vapor-deposition- (CVD-) assembled graphene
      monolayer on hexagonal boron nitride (h-BN) substrate. Graphene-channel field
      effect transistors (GFETs) were fabricated on ultra-thin h-BN multilayers to
      screen out carrier scattering from the underlying SiO2 substrate. To explore the
      transport phenomena, we use three different approaches to extract carrier
      mobility, namely, effective carrier mobility (MUFE), intrinsic carrier mobility
      (MU), and field-effect mobility (MUFE). A comparative study has been conducted
      based on the electrical characterization results, uncovering the impacts of
      supporting substrate material and device geometry scaling on carrier mobility in
      GFETs with CVD-assembled graphene as the active channel.

PMID- 22414954
TI  - Varicella zoster virus infection during chemotherapy in solid cancer patients.
AB  - BACKGROUND: Varicella zoster virus (VZV) infection is a representative
      opportunistic infection in patients with hematological malignancies, with a high
      incidence of 30-50%. Many studies on the risk factors of VZV infection in this
      patient group have been conducted. However, few data have been reported exploring
      VZV infection during systemic chemotherapy in solid cancer patients. PATIENTS AND
      METHODS: We retrospectively analyzed 92 patients diagnosed with VZV infection
      between April 2001 and July 2010 during systemic chemotherapy for solid tumors.
      All patients had received antiviral prophylaxis for VZV. RESULTS: The median age
      at the time of diagnosis of VZV infection was 60.8 years (range 30.1-83.0) and
      the majority of patients (79.3%) did not have comorbidities. Eighty-one patients
      (88%) received chemotherapy for locally advanced or metastatic/recurrent disease
      and 11 (12.0%) had adjuvant chemotherapy after curative resection. Of 92
      patients, 14 (15.2%) had non-small cell lung cancer and 10 (10.9%) breast cancer.
      All patients had a median of 2 metastatic lesions (range 0-4). At the time of
      diagnosis, 55 patients (59.8%) were receiving first-line chemotherapy and 15
      (16.3%) more than third-line chemotherapy. The mean white blood cell, platelet
      and albumin level was 5,736/MUl, 205.7 * 10(3) and 3.8 mg/dl, respectively. On
      analysis for disease evaluation at the time nearest to diagnosis of VZV
      infection, only 14 patients (15.2%) revealed tumor response to chemotherapy.
      After the diagnosis of VZV infection, all patients were treated with antiviral
      agents. None of the patients experienced failure of therapy for VZV. CONCLUSION:
      We reported VZV infection during systemic chemotherapy in solid cancer patients.
      Patients may have a relatively poor tumor response to chemotherapy at the time
      nearest to diagnosis of VZV infection. A prospective or matched controlled trial
      is needed to confirm this finding.

PMID- 22414955
TI  - Functionalized electrospun nanofibers as bioseparators in microfluidic systems.
AB  - Functionalized electrospun nanofibers were integrated into microfluidic channels
      to serve as on-chip bioseparators. Specifically, poly(vinyl alcohol) (PVA)
      nanofiber mats were shown to successfully serve as bioseparators for negatively
      charged nanoparticles. Nanofibers were electrospun onto gold microelectrodes,
      which were incorporated into poly(methyl methacrylate) (PMMA) microfluidic
      devices using UV-assisted thermal bonding. PVA nanofibers functionalized with
      poly(hexadimethrine bromide) (polybrene) were positively charged and successfully
      filtered negatively charged liposomes out of a buffer solution, while negatively
      charged nanofibers functionalized with Poly(methyl vinyl ether-alt-maleic
      anhydride) (POLY(MVE/MA)) were shown to repel the liposomes. The effect of fiber
      mat thickness was studied using confocal fluorescence microscopy, determining a
      quite broad optimal range of thicknesses for specific liposome retention, which
      simplifies fiber mat production with respect to retention reliability. Finally,
      it was demonstrated that liposomes bound to positively charged nanofibers could
      be selectively released using a 4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic
      acid (HEPES)-sucrose-saline (HSS) solution of pH 9, which dramatically changes
      the nanofiber zeta potential and renders the positively charged nanofibers
      negatively charged. This is the first demonstration of functional electrospun
      nanofibers used to enable sample preparation procedures of isolation and
      concentration in lab-on-a-chip devices. This has far reaching impact on the
      ability to integrate functional surfaces and materials into microfluidic devices
      and to significantly expand their ability toward simple lab-on-a-chip devices.

PMID- 22414956
TI  - Avidity-based extracellular interaction screening (AVEXIS) for the scalable
      detection of low-affinity extracellular receptor-ligand interactions.
AB  - Extracellular protein:protein interactions between secreted or membrane-tethered
      proteins are critical for both initiating intercellular communication and
      ensuring cohesion within multicellular organisms. Proteins predicted to form
      extracellular interactions are encoded by approximately a quarter of human genes,
      but despite their importance and abundance, the majority of these proteins have
      no documented binding partner. Primarily, this is due to their biochemical
      intractability: membrane-embedded proteins are difficult to solubilise in their
      native conformation and contain structurally-important posttranslational
      modifications. Also, the interaction affinities between receptor proteins are
      often characterised by extremely low interaction strengths (half-lives < 1
      second) precluding their detection with many commonly-used high throughput
      methods. Here, we describe an assay, AVEXIS (AVidity-based EXtracellular
      Interaction Screen) that overcomes these technical challenges enabling the
      detection of very weak protein interactions (t(1/2) <= 0.1 sec) with a low false
      positive rate. The assay is usually implemented in a high throughput format to
      enable the systematic screening of many thousands of interactions in a convenient
      microtitre plate format (Fig. 1). It relies on the production of soluble
      recombinant protein libraries that contain the ectodomain fragments of cell
      surface receptors or secreted proteins within which to screen for interactions;
      therefore, this approach is suitable for type I, type II, GPI-linked cell surface
      receptors and secreted proteins but not for multipass membrane proteins such as
      ion channels or transporters. The recombinant protein libraries are produced
      using a convenient and high-level mammalian expression system, to ensure that
      important posttranslational modifications such as glycosylation and disulphide
      bonds are added. Expressed recombinant proteins are secreted into the medium and
      produced in two forms: a biotinylated bait which can be captured on a
      streptavidin-coated solid phase suitable for screening, and a pentamerised enzyme
      tagged (beta-lactamase) prey. The bait and prey proteins are presented to each
      other in a binary fashion to detect direct interactions between them, similar to
      a conventional ELISA (Fig. 1). The pentamerisation of the proteins in the prey is
      achieved through a peptide sequence from the cartilage oligomeric matrix protein
      (COMP) and increases the local concentration of the ectodomains thereby providing
      significant avidity gains to enable even very transient interactions to be
      detected. By normalising the activities of both the bait and prey to
      predetermined levels prior to screening, we have shown that interactions having
      monomeric half-lives of 0.1 sec can be detected with low false positive rates.

PMID- 22414957
TI  - Epiretinal membrane after pars plana vitrectomy for primary pseudophakic or
      aphakic rhegmatogenous retinal detachment: incidence and outcomes.
AB  - PURPOSE: To compare outcomes of eyes that did or did not develop an epiretinal
      membrane (ERM) after repair of primary pseudophakic or aphakic rhegmatogenous
      retinal detachment by pars plana vitrectomy alone. METHODS: Interventional,
      prospective, consecutive case series. Of 312 consecutive eyes that underwent pars
      plana vitrectomy for primary rhegmatogenous retinal detachment, 28 (8.97%)
      developed ERM during the postoperative period. Best-corrected visual acuity
      (BCVA) and fundus examinations were performed 1 month and 3, 6, and 12 months
      postoperatively. RESULTS: Eyes with an ERM more often had a break at the equator
      (odds ratio, 3.92; 95% confidence interval, 1.3-11.2; P < 0.011). At ERM
      diagnosis, BCVA ranged from 20/400 to 20/25 with a mean of 20/100 (0.75 logarithm
      of the minimum angle of resolution), and BCVA at the final visit ranged from
      20/200 to 20/25 with a mean of 20/63 (0.53 logarithm of the minimum angle of
      resolution). Of the 22 eyes that underwent surgical removal of the ERM, BCVA was
      >= 20/40 in 5 (22.7%) before the surgical procedure and in 13 (59%) at the final
      follow-up visit. CONCLUSION: The incidence of ERM after pars plana vitrectomy
      alone for the repair of primary pseudophakic or aphakic rhegmatogenous retinal
      detachment was similar to reported incidences after scleral buckling. Best
      corrected visual acuity improved after surgical removal of ERM, although eyes
      with the macula detached had lower final BCVA.

PMID- 22414958
TI  - Retreatment with anti-vascular endothelial growth factor therapy based on changes
      in visual acuity after initial stabilization of neovascular age-related macular
      degeneration: 3-year follow-up results.
AB  - PURPOSE: To evaluate the 3-year therapeutic benefit of intravitreal bevacizumab
      in neovascular related macular degeneration (nAMD) in a standard clinical setting
      involving 3 initial injections and a pro re nata regimen as recommended in the
      PRONTO study. METHODS: In this interventional clinical study, 181 eyes of 160
      consecutive patients with active neovascular related macular degeneration meeting
      recommended criteria for inclusion and protocol criteria for anti-vascular
      endothelial growth factor therapy undergoing intravitreal bevacizumab monotherapy
      were observed. Data of treatment-naive eyes (Group 1, n = 114) were analyzed
      separately from eyes that had undergone previous photodynamic therapy plus
      intravitreal triamcinolone (Group 2, n = 67). Re-treatment criteria were based on
      clinical outcome following the official European label regimen. After 1 year of
      continuous service at an academic referral center, follow-up was performed in
      private practices in collaboration with the referral center. Main outcome
      parameters were best-corrected visual acuity and central retinal thickness.
      RESULTS: After 3 years, best-corrected visual acuity decreased in the overall
      population (0.23 +/- 0.16 to 0.16 +/- 0.21. P = 0.002) and in both groups
      compared with baseline (0.24 +/- 0.21 to 0.17 +/- 0.21, Group 1, P = 0.03; 0.22
      +/- 0.19 to 0.16 +/- 0.21, Group 2, P > 0.05), whereas central retinal thickness
      increased in the overall population (291 +/- 92 to 319 +/- 110 MUm, P = 0.01) and
      in both groups (291 +/- 96 to 325 +/- 117 MUm, Group 1, P > 0.05; 290 +/- 83 to
      308 +/- 96 MUm, Group 2, P > 0.05) because of chronic cystic degeneration changes
      of the macula. Mean treatment rate was 5.1 +/- 3.9 (Group 1) versus 3.7 +/- 2.7
      (Group 2, P = 0.01). Five cases of severe intraocular inflammation after
      intravitreal bevacizumab were documented. DISCUSSION: While the functional and
      morphological benefits persisted for the first year after intravitreal
      bevacizumab treatment, after this time both functional and morphologic results
      were disappointing during long-term follow-up with visual acuity loss as the main
      retreatment criterion. After stabilization of the disease, a monthly follow-up of
      optical coherence tomography and re-treatment based on morphologic, clinical, and
      vision outcomes may increase the efficacy in patients with neovascular related
      macular degeneration under anti-vascular endothelial growth factor treatment.

PMID- 22414959
TI  - Missense substitutions associated with behavioural disturbances in Alzheimer's
      disease (AD).
AB  - Behavioural and psychological symptoms in dementia, or BPSD, occur in the
      majority of Alzheimer's disease (AD) patients. They are associated with
      considerable patient morbidity and greater care-giver stress. There is some
      evidence suggesting that BPSD have a genetic component and a large number of
      studies have examined the association of candidate genes with these symptoms.
      This review provides a comprehensive summary of all the published studies
      investigating the association of candidate gene missense substitutions with BPSD.
      Missense substitutions could potentially alter protein function or render the
      protein non-functional, resulting in phenotypic consequences. More than 80
      studies investigating the association of 8 missense substitutions in 7 genes with
      BPSD were identified. However, results of these studies are contradictory and do
      not provide firm support for these associations. Larger studies and more
      systematic approaches will delineate the association of missense substitutions
      with behavioural symptoms in AD.

PMID- 22414960
TI  - The role of Nogo-A in neuroregeneration: a review.
AB  - Nogo, also known as Reticulon-4, is a protein that is specific to the central
      nervous system (CNS), and has been identified as an inhibitor of neurite
      outgrowth. Nogo-A is the largest member of the Nogo family and is responsible for
      inhibition of CNS regeneration. The structural information and biological
      functions of Nogo family members are reviewed in this study. The Nogo-66 receptor
      (NgR), a membrane protein which binds to Nogo, may play an important role in
      signal transduction for several myelin-associated inhibitors. The discovery of
      the Nogo family and the NgR provides an opportunity to develop interventions to
      promote axonal regeneration in the CNS after brain injury. Basic and clinical
      research of Nogo has increased our understanding of the mechanisms underlying
      spinal cord injury, multiple sclerosis, and neuroregenerative diseases.
      Understanding the biological functions of Nogo family members may open up a new
      avenue for the development of therapeutic agents. The anatomical and biological
      plastic changes are reviewed in animal models of injuries in the adult CNS. The
      role of Nogo A in neuroregeneration, and the mechanisms underlying functional
      recovery after CNS injury, are also detailed in this review.

PMID- 22414961
TI  - Effects of chronic clozapine administration on markers of arachidonic acid
      cascade and synaptic integrity in rat brain.
AB  - BACKGROUND: The mode of action of clozapine, an atypical antipsychotic approved
      for treating schizophrenia (SZ) and used for bipolar disorder (BD) mania, remains
      unclear. We tested for overlap with the actions of the mood stabilizers, lithium,
      carbamazepine and valproate, which downregulate arachidonic acid (AA) cascade
      markers in rat brain and upregulate BDNF. AA cascade markers are upregulated in
      BD and SZ postmortem BD brain in association with neuroinflammation and synaptic
      loss, while BDNF is decreased. METHODS: Rats were injected intraperitoneally with
      a therapeutically relevant dose of clozapine (10 mg/kg/day) or with saline for 30
      days, and AA cascade and synaptic markers and BDNF were measured in the brain.
      RESULTS: Compared with saline-injected rats, chronic clozapine increased brain
      activity, mRNA and protein levels of docosahexaenoic acid (DHA)-selective calcium
      independent phospholipase A2 type VIA (iPLA2), mRNA and protein levels of BDNF
      and of the postsynaptic marker, drebrin, while decreasing cyclooxygenase (COX)
      activity and concentration of prostaglandin E2 (PGE2), a proinflammatory AA
      metabolite. Activity and expression of AA-selective calcium-dependent cytosolic
      cPLA2 type IVA and of secretory sPLA2 Type II were unchanged. CONCLUSIONS: These
      results show overlap with effects of mood stabilizers with regard to
      downregulation of COX activity and PGE2 and to increased BDNF and suggest a
      common action against the reported neuropathology of BD and SZ. The increased
      iPLA2 expression following clozapine suggests increased production of anti
      inflammatory DHA metabolites, and, with increased BDNF and drebrin, clear
      neuroprotective action.

PMID- 22414963
TI  - Regulatory RNA-binding proteins in senescence.
AB  - The expression of senescence-associated genes, which governs the progression and
      the maintenance of senescence, is regulated at multiple levels. Apart from the
      transcriptional mechanisms that control cellular senescence, studies over the
      past decade have revealed that post-transcriptional gene regulation, especially
      through changes in mRNA turnover and translation, critically influences protein
      expression patterns in the senescent cell. Among the post-transcriptional
      regulatory factors, RNA-binding proteins (RBPs) are particularly influential in
      the establishment of senescence-associated protein profiles. In this review, I
      discuss the current knowledge of the role of RBPs in cellular senescence and the
      molecular mechanisms that regulate their function.

PMID- 22414962
TI  - Altered locomotor and stereotyped responses to acute methamphetamine in
      adolescent, maternally separated rats.
AB  - RATIONALE: Neonatal maternal separation (MS) has been used to model the effects
      of early life stress in rodents. MS alters behavioral responses to a variety of
      abused drugs, but few studies have examined its effects on methamphetamine
      sensitivity. OBJECTIVES: We sought to determine the effects of MS on locomotor
      and stereotyped responses to low-to-moderate doses of methamphetamine in male and
      female adolescent rats. METHODS: Male and female rat pups were subjected to 3 h
      per day of MS on postnatal days (PN) 2-14 or a brief handling control procedure
      during the same period. During adolescence (approximately PN 40), all rats were
      tested for locomotor activity and stereotyped behavior in response to acute
      methamphetamine administration (0, 1.0, or 3.0 mg/kg, s.c.). RESULTS: MS rats of
      both sexes exhibited increased locomotor activity in a novel environment,
      relative to handled controls. MS increased the locomotor response to
      methamphetamine (METH), and this effect occurred at different doses for male (3.0
      mg/kg) and female (1.0 mg/kg) rats. MS also increased stereotyped behavior in
      response to METH (1.0 mg/kg) in both sexes. CONCLUSIONS: MS enhances the
      locomotor response to METH in a dose- and sex-dependent manner. These results
      suggest that individuals with a history of early life stress may be particularly
      vulnerable to the psychostimulant effects of METH, even at relatively low doses.

PMID- 22414965
TI  - The structure and chemistry of tris(pentafluorophenyl)borane protected
      mononuclear nitridotitanium complexes.
AB  - Treatment of TiCl(NMe(2))(3) with H(3)N.B(C(6)F(5))(3) results in N-H activation
      and ligand exchange to yield the structurally characterised salt
      [TiCl(NMe(2))(2)(NMe(2)H)(2)](+)[Ti[triple
      bond]NB(C(6)F(5))(3)(Cl)(2)(NMe(2)H)(2)](-). Cation exchange with [Me(4)N]Cl,
      [Ph(4)P]Cl and [(PhCH(2))Ph(3)P]Cl yields the respective ammonium and phosphonium
      salts of the [Ti[triple bond]NB(C(6)F(5))(3)(Cl)(2)(NMe(2)H)(2)](-) anion. X-ray
      crystallography reveals that the essential trigonal bipyramidal geometry and
      composition of the anion is retained in each of these salts despite some minor
      variations in the Ti-N-B angle and the nature of the interionic interactions.
      Electronic investigation by DFT calculations confirmed the Ti-N triple bond
      character implied by the experimentally determined bond length, with the HOMO and
      HOMO-1 having Ti-N pi-bonding character. The dimethylamine ligands of the anion
      resist substitution by moderate bases but can be displaced by pyridine to give a
      pentacoordinate anion. In contrast, addition of 2,2'-bipyridyl gives a neutral
      octahedral complex. Treatment of the pyridine complex with TlCp results in the
      formation of a four coordinate anionic cyclopentadienyl complex.

PMID- 22414964
TI  - Equivalent effects on fecal reactive oxygen species generation with oral
      supplementation of three iron compounds: ferrous sulfate, sodium iron EDTA and
      iron polymaltose.
AB  - BACKGROUND: In any context of iron supplementation in the prenatal prophylaxis or
      therapeutic dosage range, a large amount will remain unabsorbed and pass through
      the intestinal tract into the colonic digesta possibly causing increased
      oxidation. AIM: To compare the generation of fecal reactive oxygen species (ROS)
      in situ after daily consumption of 100 mg of elemental iron in three frequently
      used forms of iron supplements. METHODS: Ten healthy, iron-repleted adult males
      were investigated before and during supplementation with three oral iron
      compounds: 100 mg of oral iron were given as ferrous sulfate, Na Fe-EDTA and iron
      polymaltose for 6 days to each subject in an individually stratified sequence.
      Stool samples were collected and analyzed for iron content and the in situ
      generation of fecal ROS. RESULTS: Significant increases in fecal ROS generation
      were observed during oral iron supplementation. No statistical differences were
      seen in either residual concentrations of non-heme iron in stool or the level of
      fecal ROS generation between the three Fe compounds. There was, however, a
      significant association between the iron concentration in the stool and ROS
      generation. CONCLUSION: In spite of the differences in their chemical
      characteristics, none of the three distinct iron complexes reduced oxidative
      stress in the intestinal lumen.

PMID- 22414966
TI  - Nickel, copper, and zinc centered ruthenium-substituted porphyrins: effect of
      transition metals on photoinduced DNA cleavage and photoinduced melanoma cell
      toxicity.
AB  - Coordination of two [Ru(bipy)(2)Cl](+) moieties (where bipy = 2,2'-bipyridine) to
      the pyridyl nitrogens in the 5,10-positions of meso-5,10,15-(4-pyridyl)-20
      (pentafluorophenyl)porphyrin gives the diruthenium porphyrin complex I. Insertion
      of nickel(II), copper(II), and zinc(II) into the porphyrin center gives the
      complexes II-IV, respectively. Electronic transitions associated with the
      ruthenium porphyrin include an intense Soret band and four less intense Q-bands
      in the visible region of the spectrum. An intense pi-pi* transition in the UV
      region associated with the bipyridyl groups and a metal-to-ligand charge transfer
      (MLCT) band appearing as a shoulder to the Soret band are also observed. A shift
      of the Soret band and collapse of the Q-bands into one band is observed upon
      insertion of the metal ions into the porphyrin center. Electrochemical properties
      associated with the complexes include a redox couple in the cathodic region
      attributed to the porphyrin and a redox couple in the anodic region due to the
      Ru(III/II) couple. DNA titrations of the complexes indicate that they interact
      strongly with DNA potentially through an intercalation mechanism. Irradiation of
      aqueous solutions of the complexes and supercoiled DNA at a 5:1 base pair to
      complex ratio with visible light above 400 nm shows nicking of DNA for the
      nickel(II) and copper(II) complexes and photocleavage of DNA for the zinc(II)
      complex. Cell studies with dermal skin (normal) fibroblast and melanoma cells
      indicate that the free base porphyrin(I) is toxic to both normal and melanoma
      cells, while the nickel(II) and copper(II) complexes, II and III, are non-toxic
      to both cell lines when irradiated with a tungsten lamp. The zinc(II) complex,
      IV, is non-toxic to normal cells but toxic to melanoma cells when irradiated
      under the same conditions.

PMID- 22414967
TI  - National patterns in human papillomavirus vaccination: an analysis of the
      National Survey of Family Growth.
AB  - Human papillomavirus (HPV) vaccine has shown effectiveness for girls and young
      women. Despite this, there are population disparities in vaccine utilization
      rates. The purpose of this study was to evaluate maternal correlates of HPV
      vaccination among their adolescent daughters using a nationally-representative
      population-based sample, emphasizing race/ethnicity-specific disparities and
      barriers. Mothers of 9-18 y-old girls having heard of HPV vaccine and completing
      the HPV vaccine survey module from the 2006-2008 National Survey of Family Growth
      (NSFG) (n = 444) were analyzed for maternally-reported adolescent HPV vaccination
      and maternal intent to vaccinate her adolescent daughter if no dose had been
      received. Correlates of uptake and intent were examined using multivariate
      logistic regression. 27% of mothers (n = 98) reported that their daughters were
      vaccinated against HPV. Independent correlates of vaccination included African
      American race (adjusted odds ratio (AOR),0.29; 95% confidence interval (CI),0.11
      0.77), and living below the poverty level (AOR,4.43; 95%CI, 1.53-12.82). 46% (n =
      152) of mothers of non-vaccinated daughters intended to vaccinate them.
      Correlates of maternal intention included maternal pelvic exam history (AOR,0.06;
      95%CI, 0.007-0.51), multiple male lifetime sexual partners (AOR,3.22 ; 95% CI,
      1.34-7.76), religiosity (AOR,0.37; 95% CI,0.16-0.87) and acceptability of
      premarital sex among 18 y-olds (AOR,2.45; 95% CI, 1.16-5.20). In conclusion, HPV
      vaccination initiation among adolescent daughters of mothers participating in the
      NSFG continues to lag among African-American participants. However, no
      racial/ethnic differences in maternal intent-to-vaccinate her daughter were
      detected. Future interventions need to address specific maternal barriers to
      vaccine uptake and how these may differ from vaccine intention.

PMID- 22414968
TI  - Clinical trials in elderly ovarian cancer patients - does it make sense?

PMID- 22414969
TI  - Treatment of elderly ovarian cancer patients in the context of controlled
      clinical trials: a joint analysis of the AGO Germany experience.
AB  - BACKGROUND: Age remains a negative prognostic factor in ovarian cancer (OC). 3
      separate analyses by the AGO (Arbeitsgemeinschaft Gynaekologische Onkologie) give
      insight into the treatment of elderly patients (EPs) in the context of controlled
      clinical trials (CCTs). METHODS: 1 retrospective study evaluated the reasons for
      non-enrolment into CCTs of patients with advanced OC in AGO centers. 2 other
      exploratory age-specific analyses of a phase III trial in advanced OC treated
      with platinum/ paclitaxel evaluated (1) feasibility, toxicity and quality of life
      (QoL) and (2) the clinical outcome. RESULTS: Non-study patients were
      significantly older (66.7 vs. 57.2 years). Reasons for non-enrolment were
      predominantly predefined exclusion criteria, numeric age, and the patient's
      decision. The phase III trial confirmed an under-representation of EPs. Cycle
      delivery was significantly lower and discontinuation more frequent in EPs than in
      younger patients (YPs), although QoL, toxicity, cycle delays, and dose reductions
      were comparable. Delivery of cycles was prognostically significant in EPs but not
      YPs. The survival advantage of YPs remained significant even in completely
      debulked patients. CONCLUSION: There is some kind of investigator reservation for
      the treatment of EPs, which not only applies for the enrolment into clinical
      trials but also for the treatment, even under CCT conditions, with impact on
      outcome.

PMID- 22414970
TI  - Clinical significance of diffuse hepatic visualization and thyroid bed uptake on
      post-ablative iodine-131 whole body scan in differentiated thyroid cancer.
AB  - BACKGROUND: The aim of this study was to investigate whether diffuse hepatic and
      thyroid bed uptake of (131)I on post-ablative whole body scans (PAWBS) of
      patients with differentiated thyroid cancer (DTC) have any relevance for clinical
      outcome and parameters. PATIENTS AND METHODS: We retrospectively reviewed 838
      patients with DTC, who were treated at Pusan National University Hospital from
      2004 to 2009. Grades of hepatic and thyroid bed uptake on (131)I whole body scan
      were classified from 0 to 3 by visual assessment. Recurrence-free survival was
      evaluated with the Kaplan-Meier method and Cox regression analysis. RESULTS: Male
      patients having tumors larger than 4 cm (p = 0.005), multiple tumor foci (p <
      0.001), involved margins (p = 0.006), and a higher TNM stage (p < 0.001) were
      more likely to relapse. Thyroid bed grade (p < 0.001) and liver uptake grade (p =
      0.002) were also revealed as significant prognostic factors. Intense thyroid bed
      uptake and faint hepatic activity were related to poor prognosis. CONCLUSIONS: We
      suggest that increased retention of (131)I in the thyroid bed and less
      visualization of liver on PAWBS mean poor prognosis. This would be related to the
      amount of remnant thyroid tissue and ineffective destruction of it.

PMID- 22414971
TI  - Expression of vascular endothelial growth factor C correlates with lymphatic
      vessel density and prognosis in human gastroesophageal junction carcinoma.
AB  - BACKGROUND: The present study clarifies the clinical significance of vascular
      endothelial growth factor C (VEGF-C) in patients with gastroesophageal junction
      carcinoma treated with curative resection, as well as the correlation between
      VEGF-C expression and lymphatic vessel density (LVD). PATIENTS AND METHODS: VEGF
      C expression was immunohistochemically detected in 128 patients with
      gastroesophageal junction carcinoma, who underwent curative surgical resection.
      The mean optical density (MOD) was measured to represent the expression level of
      VEGF-C. The lymphatic vessels were labeled with D2-40 to calculate LVD. The
      association between MOD and LVD and clinicopathological parameters as well as the
      prognosis were analyzed. RESULTS: Both VEGF-C expression and LVD were correlated
      with nodal metastasis and clinical stage (p < 0.05). For the high (MOD > 0.18)
      and low (MOD <= 0.18) VEGF-C group, the mean LVD was 16.9 +/- 5.96 and 13.6 +/-
      5.58, respectively (p = 0.002), and the mean number of positive resected lymph
      nodes was 2.9 +/- 2.44 and 2.0 +/- 2.36, respectively (p = 0.025). For the high
      (LVD > 13) and low (LVD <= 13) LVD group, the mean number of positive resected
      lymph nodes was 3.0 +/- 2.34 and 1.9 +/- 2.43, respectively (p = 0.010). In
      univariate analysis, both high expression of VEGF-C and a high LVD level were
      statistically associated with poor disease-free survival (p = 0.000).
      Multivariate analysis showed that VEGF-C, nodal metastasis, depth of tumor
      invasion, postoperative chemotherapy, and resection extent were independent
      survival predictors (p < 0.05). CONCLUSIONS: Increased expression of VEGF-C is
      correlated with high levels of LVD and poorer treatment outcome.

PMID- 22414972
TI  - Factors influencing the hormone receptor and HER2 levels in breast cancer: a
      population-based analysis.
AB  - BACKGROUND: Breast cancer (BC) is regarded as a heterogeneous disease that is
      classified into various molecular subtypes using gene expression analysis. The
      aim of this study was to perform a population-based analysis of the prevalence of
      molecular BC subtypes in Turkish women, and to determine their association with
      known prognostic and clinicopathological factors. PATIENTS AND METHODS: A total
      of 1,025 cases with operable BC, who presented within a 2 year period (2006
      2007), were evaluated. Estrogen receptor (ER), progesterone receptor (PR), and
      HER2 expression were determined immunohistochemically. RESULTS: 68.3% of patients
      were ER-positive, and 71.5% were PR-positive. Among the 28.3% of HER2-positive
      tumors, the majority (19.2%) stained +++. Almost 50% of the tumors were ER+ PR+
      HER2-, which makes this the predominant tumor type. For both triple-negative and
      positive status, a ratio of approximately 10% was determined. For ER+ PR+ HER2-,
      tumor histology, tumor stage, and histological grade were found to be correlated.
      Menopausal status, obesity, tumor histology, histological grade, in-situ
      component, and lymphovascular invasion were associated with triple-positive
      tumors. A significant relationship was found between the variables - including
      histological grade, in-situ component, and involvement of axillary lymph nodes -
      and triple-negative status. CONCLUSION: A more thorough understanding of the
      biological background and underlying mechanisms of BC may allow the development
      of rational targeted approaches and therapies.

PMID- 22414973
TI  - Trisomy 8 is the most frequent cytogenetic abnormality in de novo myelodysplastic
      syndrome in China.
AB  - BACKGROUND: Cytogenetic abnormalities have been detected in 40-60% of patients
      with de novo myelodysplastic syndrome (MDS). Some reports suggest that Asian and
      Western MDS patients have different cytogenetic features. PATIENTS AND METHODS:
      We retrospectively analyzed 168 patients with de novo MDS and compared our
      results with other Chinese centers to investigate the prevalence and cytogenetic
      characteristics of MDS in China. RESULTS: In our study, chromosome abnormalities
      were detected in 40.48% of patients (68/168). Although the median survival time
      did not differ between younger and older (>=60 years) patients (p = 0.969),
      survival curves based on International Prognostic Scoring System (IPSS)
      cytogenetic groups and WHO Classification-Based Prognostic Scoring System (WPSS)
      risk groups were significantly different (p < 0.001). Survival differences were
      observed between patients in the normal karyotype group, sole trisomy 8 group,
      and poor cytogenetic group according to IPSS (p < 0.001). In agreement with the
      results from 2 other large Chinese centers, trisomy 8 was the most detected
      cytogenetic abnormality, with a prevalence of 14.21%. CONCLUSION: Trisomy 8,
      categorized as intermediate cytogenetic risk group in our study, is the most
      frequent cytogenetic abnormality in de novo MDS in China.

PMID- 22414974
TI  - Comparative analysis of tumor markers and evaluation of their predictive value in
      patients with colorectal cancer.
AB  - BACKGROUND: We evaluated the feasibility of CEA/CK20 mRNA and CEA/CA19-9 proteins
      as tumor markers for colorectal cancer by detecting tumor-specific mRNAs in
      circulating tumor cells and secreted tumor-specific proteins in the peripheral
      blood of colorectal cancer patients. PATIENTS AND METHODS: Peripheral blood was
      obtained from 23 healthy volunteers and 46 colorectal cancer patients on the day
      of initiation of adjuvant chemotherapy after surgery (stages I-III, n = 27) or on
      the first day of chemotherapy after diagnosis (stage IV, n = 19). Levels of
      CEA/CK20 mRNA in peripheral blood mononuclear cells (PBMCs) were determined with
      quantitative real-time reverse transcription polymerase chain reaction, and serum
      CEA/CA19-9 protein levels were determined by radioimmunoassay. RESULTS: The
      detection sensitivity of CK20 mRNA was approximately 1 tumor cell in 1 * 10(7)
      PBMCs, and that of CEA mRNA was approximately 1 tumor cell in 1 * 10(6) PBMCs.
      Patients with stage IV colorectal cancer had higher levels of CEA mRNA, CK20
      mRNA, and serum CEA than patients at stages I-III. Peripheral blood CEA mRNA
      levels were predictive of overall survival, while serum protein levels of CEA and
      CA19-9 had no predictive value. CONCLUSION: Peripheral blood CEA mRNA is a useful
      marker of overall survival in colorectal cancer patients, that is sensitive and
      specific.

PMID- 22414975
TI  - Malignant perivascular epithelioid cell tumor of the mesentery: a case report and
      literature review.
AB  - BACKGROUND: Perivascular epithelioid cell tumors (PEComas) are very rare
      mesenchymal neoplasms, and have been found in various organs such as the liver,
      kidney, falciform ligament, uterus, uterine cervix, and both the small and large
      bowel. However, only 3 cases of mesenteric PEComa have been described in the
      literature so far. The treatment and prognosis of malignant mesenteric PEComas
      are discussed. CASE REPORT: We report the case of a 59-year-old man diagnosed
      with PEComa. He underwent segmental resection of the jejunum and tumor resection.
      Malignant mesenteric PEComa was confirmed on the basis of clinicopathological
      features. Tumor resection was followed by concurrent chemoradiotherapy.
      CONCLUSION: Besides surgery, no effective treatment for malignant PEComa has been
      established thus far because of the rarity of this tumor. Here, we report our
      experience of treating a malignant mesenteric PEComa using surgery and subsequent
      adjuvant therapy, which effectively controlled disease progression and prevented
      local recurrence.

PMID- 22414976
TI  - Effectiveness and safe use of modified FOLFOX-6 for metastatic gastric cancer
      with signet ring cell components complicated by disseminated intravascular
      coagulation and diffuse bone marrow carcinomatosis.
AB  - We report the case of a 62-year-old woman with a metastatic gastric cancer
      complicated by diffuse bone marrow carcinomatosis, disseminated intravascular
      coagulation (DIC) and microangiopathic hemolytic anemia (MHA) treated by modified
      FOLFOX-6 as front-line chemotherapy regimen. This chemotherapy showed clinical,
      morphological and biological efficiency and safety in this rare and severe
      hematological complication at initial diagnosis. Furthermore, this is the first
      case of diffuse bone carcinomatosis from a gastric cancer to be monitored by
      positron emission tomography integrated computed tomography (PET-CT) scan using
      18-fluorodeoxyglucose (18-FDG).

PMID- 22414977
TI  - Hoarseness: an unusual complication of port-A catheter perforation.
AB  - BACKGROUND: A port-A catheter implantation for cancer patients is popular as a
      route for chemotherapy. Potential complications exist, such as perforation during
      chemotherapeutic agent infusion, especially when the port-A tip is incorrectly
      positioned or when it is in long-term use. CASE REPORT: We report on a patient
      who presented with hoarseness as a result of port-A catheter perforation-related
      mediastinitis subsequent to chemotherapeutic agent infusion through the catheter.
      CONCLUSIONS: Hoarseness is a rare complication of port-A perforation and
      extravasation. To avoid perforation, the tip of the catheter should be located in
      a high-flow vessel, such as the distal superior vena cava rather than higher in
      the caval vein, to prevent a locally increased concentration of drugs. We also
      recommend that a venogram be arranged if extravasation is suspected.

PMID- 22414978
TI  - Quiz case: a 19-year-old woman with hypercalcemia and abdominal pain.

PMID- 22414979
TI  - Pregnancy after successful cancer treatment: what needs to be considered?
AB  - Over the last decade, advances in oncology led to improved treatment results and
      increasing numbers of long-term cancer survivors. Fulfilling the desire to have
      children is important for many patients after cancer treatment. Consequently,
      oncologists, gynecologists and obstetricians are seeing more patients who wish to
      conceive after treatment. The necessary prerequisites that should be considered
      when supporting a planned pregnancy after cancer treatment are discussed in this
      article. The possible consequences of chemotherapy and radiotherapy on the course
      of pregnancy and the health of the offspring, as well as the interactions between
      cancer and pregnancy, are reviewed with the focus on childhood cancer, malignant
      lymphomas, and breast cancer. Despite chemo- or radiotherapy, neither the
      teratogenic risk nor the risk of adventitious cancers appears to be increased for
      the offspring of cancer survivors. However, there is a slightly higher risk of
      miscarriage after chemotherapy. In case of radiation to the uterus, there is a
      higher risk of premature birth, intrauterine growth retardation, and increased
      perinatal mortality. The effect is more pronounced after prepubertal radiation
      than for postpubertal radiation. The former cancer patient's desire to conceive
      can nevertheless be supported, given that pregnancy and birth are closely
      monitored.

PMID- 22414980
TI  - Breast-conserving therapy for early-stage breast cancer in Chinese women: a meta
      analysis of case-control studies.
AB  - BACKGROUND: Breast cancer has a high incidence worldwide, while Chinese patients
      have some special characteristics compared to Western patients. A meta-analysis
      was carried out to determine the effectiveness of breast-conserving therapy (BCT)
      or mastectomy therapy (MT) for early-stage breast cancers in Chinese women.
      METHODS: A fully recursive literature search was conducted in the Chinese
      Biomedical Literature Database. Case-control trials were considered for
      inclusion. Analyses were carried out using the Review Manager software (RevMan,
      version 5.0). RESULTS: The meta-analysis showed that the 3-year or 5-year overall
      survival, the locoregional recurrence rate, and the metastasis rate were not
      statistically different between the BCT group and the MT group, but the
      complication recurrence rate increased in the MT group. Subgroup analysis
      indicated that no significant differences were observed in the affected limb
      swelling recurrence rate between the BCT group and the MT group. CONCLUSIONS: BCT
      was the better choice than MT for Chinese women with early-stage breast cancer.

PMID- 22414982
TI  - Urine metabolomics combined with the personalized diagnosis guided by Chinese
      medicine reveals subtypes of pre-diabetes.
AB  - The prevalence of type 2 diabetes continuously increases globally. A personalized
      strategy applied in the pre-diabetic stage is vital for diabetic prevention and
      management. The personalized diagnosis of Chinese Medicine (CM) may help to
      stratify the diabetics. Metabolomics is regarded as a potential platform to
      provide biomarkers for disease-subtypes. We designed an explorative study of 50
      pre-diabetic males, combining GC-MS urine metabolomics with CM diagnosis in order
      to identify diagnostic biomarkers for pre-diabetic subtypes. Three CM physicians
      reached 85% diagnosis consistency resulting in the classification of 3 pre
      diabetic groups. The urine metabolic patterns of groups 1 'Qi-Yin deficiency' and
      2 'Qi-Yin deficiency with dampness' (subtype A) and group 3 'Qi-Yin deficiency
      with stagnation' (subtype B) were clearly discriminated. The majority of
      metabolites (51%), mainly sugars and amino acids, showed higher urine levels in
      subtype B compared with subtype A. This indicated more disturbances of
      carbohydrate metabolism and renal function in subtype B compared with subtype A.
      No differences were found for hematological and biochemical parameters except for
      levels of glucose and gamma-glutamyltransferase that were significantly higher in
      subtype B compared with subtype A. This study proved that combining metabolomics
      with CM diagnosis can reveal metabolic signatures for pre-diabetic subtypes. The
      identified urinary metabolites may be of special clinical relevance for non
      invasive screening for subtypes of pre-diabetes, which could lead to an
      improvement in personalized interventions for diabetics.

PMID- 22414981
TI  - Seaweed consumption and the risk of thyroid cancer in women:  the Japan Public
      Health Center-based Prospective Study.
AB  - Iodine is a suspected risk factor for thyroid cancer. Seaweed accounts for about
      80% of Japanese people's iodine intake. We examined the association between
      seaweed consumption and the risk of thyroid cancer in Japanese women. Women
      participating in the Japan Public Health Center-based Prospective Study (n=52
      679; age: 40-69 years) were followed up for a mean of 14.5 years; 134 new thyroid
      cancer cases, including 113 papillary carcinoma cases, were identified. Seaweed
      consumption was assessed using a food-frequency questionnaire and divided into
      three categories: 2 days/week or less (reference); 3-4 days/week; and almost
      daily. The Cox proportional hazards model was applied to estimate hazard ratios
      (HRs) and 95% confidence intervals (CIs). Seaweed consumption was clearly
      associated with an increased risk of papillary carcinoma (HR for almost daily
      consumption compared with 2 days/week or less=1.71; 95% CI: 1.01-2.90; trend
      P=0.04). After stratification for menopausal status, an increased risk was
      observed in postmenopausal women (papillary carcinoma HR for almost daily
      consumption compared with 2 days/week or less=3.81, 95% CI: 1.67-8.68; trend
      P<0.01), but not in premenopausal women (HR=0.91, 95% CI: 0.44-1.91; trend
      P=0.76). This study identified a positive association between seaweed consumption
      and the risk of thyroid cancer (especially for papillary carcinoma) in
      postmenopausal women.

PMID- 22414983
TI  - When perceptual time stands still: long percept-memory in binocular rivalry.
AB  - We have carried out binocular rivalry experiments with a large number of subjects
      to obtain high quality statistics on probability distribution of dominance
      duration (PDDD) for two cases where (a) the rival stimulus is continuously
      presented and (b) the rival stimulus is periodically removed, with stimulus-on
      and stimulus-off intervals T(on) and T(off) respectively. In the present study we
      have chosen to study the regime of relatively long stimulus-on time, i.e., T(on)>
      1s, where the stimulus presentation duration is significantly longer than the
      human reaction and recognition time. In the case of periodically removed
      stimulus, the total probability for percept reversal during each of the
      successive stimulus-on intervals T(on) can be predicted using the PDDD for
      continuous viewing. More importantly, this total probability for percept reversal
      during any stimulus-on interval is independent of the length T(off) of the
      preceding blank time, which can be quite long. We argue that this suggests that,
      in the regime of long T(on) and T(off) considered here, the variables
      representing the perceptual state do not change significantly during long blank
      intervals. We discuss that these findings impose challenges to theoretical models
      which aim at describing visual perception.

PMID- 22414984
TI  - Protective embolization of the gastroduodenal artery with a one-HydroCoil
      technique in radioembolization procedures.
AB  - PURPOSE: Protective occlusion of the gastroduodenal artery (GDA) is required to
      avoid severe adverse effects and complications in radioembolization procedures.
      Because of the expandable features of HydroCoils, our goal was to occlude the GDA
      with only one HydroCoil to provide particle reflux protection. METHODS: Twenty
      three subjects with unresectable liver tumors, who were scheduled for protective
      occlusion of the GDA before radioembolization therapy, were included. The primary
      end point was to achieve a proximal occlusion of the GDA with only one detachable
      HydroCoil. Evaluated parameters were duration of deployment, and early (during
      the intervention) and late (7-21 days) occlusion rates of GDA. Secondary end
      points included complete duration of the intervention, amount of contrast medium
      used, fluoroscopy rates, and adverse effects. RESULTS: In all cases, the GDA was
      successfully occluded with only one HydroCoil. The selected diameter/length range
      was 4/10 mm in 2 patients, 4/15 mm in 6 patients, and 4/20 mm in 15 patients.
      HydroCoils were implanted, on average, 3.75 mm from the origin of the GDA (range
      1.5-6.8 mm), with an average deployment time of 2:47 (median 2:42, range 2:30
      3:07) min. In 21 (91%) of 23 patients, a complete occlusion of the GDA was
      achieved during the first 30 min after the coil implantation; however, in all
      patients, a late occlusion of the GDA was present after 6 to 29 days. No clinical
      or technical complications were reported. CONCLUSION: We demonstrated that
      occlusion of the GDA with a single HydroCoil is a safe procedure and successfully
      prevents extrahepatic embolization before radioembolization.

PMID- 22414985
TI  - US-guided femoral and sciatic nerve blocks for analgesia during endovenous laser
      ablation.
AB  - PURPOSE: Endovenous laser ablation may be associated with significant pain when
      performed under standard local tumescent anesthesia. The purpose of this study
      was to investigate the efficacy of femoral and sciatic nerve blocks for analgesia
      during endovenous ablation in patients with lower extremity venous insufficiency.
      METHODS: During a 28-month period, ultrasound-guided femoral or sciatic nerve
      blocks were performed to provide analgesia during endovenous laser ablation in
      506 legs and 307 patients. The femoral block (n = 402) was performed at the level
      of the inguinal ligament, and the sciatic block at the posterior midthigh (n =
      124), by injecting a diluted lidocaine solution under ultrasound guidance. After
      the blocks, endovenous laser ablations and other treatments (phlebectomy or foam
      sclerotherapy) were performed in the standard fashion. After the procedures, a
      visual analogue pain scale (1-10) was used for pain assessment. RESULTS: After
      the blocks, pain scores were 0 or 1 (no pain) in 240 legs, 2 or 3 (uncomfortable)
      in 225 legs, and 4 or 5 (annoying) in 41 legs. Patients never experienced any
      pain higher than score 5. The statistical analysis revealed no significant
      difference between the pain scores of the right leg versus the left leg (p =
      0.321) and between the pain scores after the femoral versus sciatic block (p =
      0.7). CONCLUSIONS: Ultrasound-guided femoral and sciatic nerve blocks may provide
      considerable reduction of pain during endovenous laser and other treatments, such
      as ambulatory phlebectomy and foam sclerotherapy. They may make these procedures
      more comfortable for the patient and easier for the operator.

PMID- 22414986
TI  - Hippocrates predicted renal cryoablation bleeding risk in patients receiving
      anticoagulation.

PMID- 22414987
TI  - Cost-effectiveness analysis of infrapopliteal drug-eluting stents.
AB  - INTRODUCTION: There are no cost-utility data about below-the-knee placement of
      drug-eluting stents. The authors determined the cost-effectiveness of
      infrapopliteal drug-eluting stents for critical limb ischemia (CLI) treatment.
      METHODS: The event-free individual survival outcomes defined by the absence of
      any major events, including death, major amputation, and target limb repeat
      procedures, were reconstructed on the basis of two published infrapopliteal
      series. The first included spot Bail-out use of Sirolimus-eluting stents versus
      bare metal stents after suboptimal balloon angioplasty (Bail-out SES).The second
      was full-lesion Primary Everolimus-eluting stenting versus plain balloon
      angioplasty and bail-out bare metal stenting as necessary (primary EES). The
      number-needed-to-treat (NNT) to avoid one major event and incremental cost
      effectiveness ratios (ICERs) were calculated for a 3-year postprocedural period
      for both strategies. RESULTS: Overall event-free survival was significantly
      improved in both strategies (hazard ratio (HR) [confidence interval (CI)]: 0.68
      [0.41-1.12] in Bail-out SES and HR [CI]: 0.53 [0.29-0.99] in Primary EES). Event
      free survival gain per patient was 0.89 (range, 0.11-3.0) years in Bail-out SES
      with an NNT of 4.6 (CI: 2.5-25.6) and a corresponding ICER of 6,518<euro> (range
      1,685-10,112<euro>). Survival gain was 0.91 (range 0.25-3.0) years in Primary EES
      with an NNT of 2.7 (CI: 1.7-5.8) and an ICER of 11,581<euro> (range, 4,945
      21,428<euro>) per event-free life-year gained. Two-way sensitivity analysis
      showed that stented lesion length >10 cm and/or DES list price >1000<euro> were
      associated with the least economically favorable scenario in both strategies.
      CONCLUSIONS: Both strategies of bail-out SES and primary EES placement in the
      infrapopliteal arteries for CLI treatment exhibit single-digit NNT and relatively
      low corresponding ICERs.

PMID- 22414988
TI  - Kinetics of the iodate reduction by hydrogen peroxide and relation with the
      Briggs-Rauscher and Bray-Liebhafsky oscillating reactions.
AB  - The iodate reduction by hydrogen peroxide in acidic solutions is part of the Bray
      Liebhafsky and Briggs-Rauscher oscillating reactions. At low hydrogen peroxide
      concentrations, typical of the Bray-Liebhafsky reaction, its rate law is -d[IO(
      )(3)]/dt = (k'(R) + k"(R)[H(+)])[IO(-)(3)][H(2)O(2)] with k'(R) = 1.3 * 10(-7)(20
      degrees ), 7.8 * 10(-7) (39 degrees ), 1.4 * 10(-5) M(-1) s(-1) (60 degrees ) and
      k"(R) = 1.5 * 10(-5) (25 degrees ), 6.2 * 10(-5) (39 degrees ), 6.3 * 10(-4) M(
      2) s(-1) (60 degrees ). It is explained by a non-radical mechanism. At high
      hydrogen peroxide concentrations, typical of the Briggs-Rauscher reaction, a new
      reaction pathway appears with a rate more than proportional to [H(2)O(2)](2) and
      nearly independent of [IO(3)(-)] > 0.01 M. This pathway is inhibited by
      scavengers of free radicals. We suggest that it has a radical mechanism starting
      with IOH + H(2)O(2)? IOOH + H(2)O and IOOH+H(2)O(2)-> IO + H(2)O+HOO.

PMID- 22414989
TI  - Preparation of regularly structured  nanotubular TiO2 thin films on ITO and 
      their modification with thin ALD-grown  layers.
AB  - Nanotubular titanium dioxide thin films were prepared by anodization of titanium
      metal films evaporated on indium tin oxide (ITO) coated glass. A facile method to
      enhance the adhesion of the titanium film to the ITO glass was developed. An
      optimum thickness of 550 nm for the evaporated titanium was found to keep the
      film adhered to ITO during the anodization. The films were further modified by
      growing amorphous titania, alumina and tantala thin films conformally in the
      nanotubes by atomic layer deposition (ALD). The optical, electrical and physical
      properties of the different structures were compared. It was shown that even 5 nm
      thin layers can modify the properties of the nanotubular titanium dioxide films.

PMID- 22414990
TI  - Why use a connectivity-based approach to study stroke and recovery of function?
AB  - The brain is organized into a set of widely distributed networks. Therefore,
      although structural damage from stroke is focal, remote dysfunction can occur in
      regions connected to the area of lesion. Historically, neuroscience has focused
      on local processing due in part to the absence of tools to study the function of
      distributed networks. In this article we discuss how a more comprehensive
      understanding of the effects of stroke can be attained using resting state
      functional connectivity BOLD magnetic resonance imaging (resting state fcMRI).
      Resting state fcMRI has a number of advantages over task-evoked fMRI for studying
      brain network reorganization in response to stroke, including the ability to
      image subjects with a broad range of impairments and the ability to study
      multiple networks simultaneously. We describe our rationale for using resting
      state connectivity as a tool for investigating the neural substrates of stroke
      recovery in a heterogeneous population of stroke patients and discuss the main
      questions we hope to answer, in particular whether resting state fcMRI measures
      in the acute phase of stroke can predict subsequent recovery. Early results
      suggest that disruption of inter-hemispheric connectivity in the somatomotor
      network and the dorsal attention network is more strongly associated with
      behavioral impairment in those domains than is intra-hemispheric connectivity
      within either the lesioned or unaffected hemisphere. We also observe in the
      somatomotor network an interesting interaction between corticospinal tract damage
      and decreased inter-hemispheric connectivity that suggests that both processes
      combine to contribute to neuromotor impairment after stroke. A connectivity-based
      approach will provide greater insight into network reorganization in the acute
      and chronic phases after stroke and will contribute to improving prognostic
      ability and the development of therapeutic interventions.

PMID- 22414992
TI  - Automatic fiber bundle segmentation in massive tractography datasets using a
      multi-subject bundle atlas.
AB  - This paper presents a method for automatic segmentation of white matter fiber
      bundles from massive dMRI tractography datasets. The method is based on a multi
      subject bundle atlas derived from a two-level intra-subject and inter-subject
      clustering strategy. This atlas is a model of the brain white matter
      organization, computed for a group of subjects, made up of a set of generic fiber
      bundles that can be detected in most of the population. Each atlas bundle
      corresponds to several inter-subject clusters manually labeled to account for
      subdivisions of the underlying pathways often presenting large variability across
      subjects. An atlas bundle is represented by the multi-subject list of the
      centroids of all intra-subject clusters in order to get a good sampling of the
      shape and localization variability. The atlas, composed of 36 known deep white
      matter bundles and 47 superficial white matter bundles in each hemisphere, was
      inferred from a first database of 12 brains. It was successfully used to segment
      the deep white matter bundles in a second database of 20 brains and most of the
      superficial white matter bundles in 10 subjects of the same database.

PMID- 22414991
TI  - Visual analytics of brain networks.
AB  - Identification of regions of interest (ROIs) is a fundamental issue in brain
      network construction and analysis. Recent studies demonstrate that multimodal
      neuroimaging approaches and joint analysis strategies are crucial for accurate,
      reliable and individualized identification of brain ROIs. In this paper, we
      present a novel approach of visual analytics and its open-source software for ROI
      definition and brain network construction. By combining neuroscience knowledge
      and computational intelligence capabilities, visual analytics can generate
      accurate, reliable and individualized ROIs for brain networks via joint modeling
      of multimodal neuroimaging data and an intuitive and real-time visual analytics
      interface. Furthermore, it can be used as a functional ROI optimization and
      prediction solution when fMRI data is unavailable or inadequate. We have applied
      this approach to an operation span working memory fMRI/DTI dataset, a
      schizophrenia DTI/resting state fMRI (R-fMRI) dataset, and a mild cognitive
      impairment DTI/R-fMRI dataset, in order to demonstrate the effectiveness of
      visual analytics. Our experimental results are encouraging.

PMID- 22414993
TI  - Neural correlates of temporal integration in face recognition: an fMRI study.
AB  - Integration of temporally separated visual inputs is crucial for perception of a
      unified representation. Here, we show that regions involved in configural
      processing of faces contribute to temporal integration occurring within a limited
      time-window using a multivariate analysis (partial least squares, PLS) exploring
      the relation between brain activity and recognition performance. During fMRI, top
      and bottom parts of a famous face were presented sequentially with a varying
      interval (0, 200, or 800 ms) or were misaligned. The 800 ms condition activated
      several regions implicated in face processing, attention and working memory,
      relative to the other conditions, suggesting more active maintenance of
      individual face parts. Analysis of brain-behavior correlations showed that better
      identification in the 0 and 200 conditions was associated with increased activity
      in areas considered to be part of a configural face processing network, including
      right fusiform, middle occipital, bilateral superior temporal areas,
      anterior/middle cingulate and frontal cortices. In contrast, successful
      recognition in the 800 and misaligned conditions, which involve analytic and
      strategic processing, was negatively associated with activation in these regions.
      Thus, configural processing may involve rapid temporal integration of facial
      features and their relations. Our finding that regions concerned with configural
      and analytic processes in the service of face identification opposed each other
      may explain why it is difficult to apply the two processes concurrently.

PMID- 22414994
TI  - Hippocampal subfield volumes correlate with memory training benefit in subjective
      memory impairment.
AB  - Although some older adults experiencing memory problems have been shown to
      benefit from cognitive training, evidence regarding who will improve from this
      type of intervention is lacking. Automated hippocampal volumetry might be used to
      foresee treatment outcomes. We hypothesized that larger hippocampal volumes are
      associated with greater memory performance changes following training, and that
      effects are selectively related to specific hippocampal subfields. 19 memory
      clinic outpatients with subjective memory impairment (mean age=60.9 years)
      underwent MRI-scanning and then followed an eight week training scheme aimed at
      improving verbal memory. We assessed verbal memory before and after training, and
      tested whether pretraining hippocampal volumes were related to memory
      improvements. To delineate regional specificity, we employed a new technique
      enabling automated volumetry of seven hippocampal subfields - including the cornu
      ammonis (CA) sectors and the dentate gyrus (DG). The results showed that larger
      hippocampal volumes before training were related to greater verbal recall
      improvements. Subfield volumetry revealed specific correlations between memory
      improvement and pretraining volumes of the left CA2/3 and CA4/DG. Depressive
      symptoms further gave a unique contribution in predicting gain of the
      intervention, independent of hippocampal volume. The results indicated that
      subjects with a stronger depressive symptom load benefited more from the
      training. A prediction model including baseline CA2/3-volume and depressive
      symptoms explained 42% of the variation in recall improvement. Our results are
      the first to suggest that hippocampal subfield volumetry is related to
      intervention outcomes in older adults experiencing memory problems. Also,
      previous studies have tended to exclude patients with concomitant depressive
      symptoms and memory complaints. The present results, however, strengthen the
      rationale and potential for cognitive intervention in these patients.

PMID- 22414995
TI  - Neurological recovery is impaired by concurrent but not by asymptomatic pre
      existing spinal cord compression after traumatic spinal cord injury.
AB  - STUDY DESIGN: An in vivo animal study to examine the influence of pre-existing or
      concurrent spinal canal stenosis (SCS) on the functional recovery after spinal
      cord injury (SCI). OBJECTIVES: To clarify whether spinal cord compression before
      or after SCI results in less favorable neurological recovery. SUMMARY OF
      BACKGROUND DATA: The influence of spinal cord compression on the neurological
      recovery after SCI remains unclear. METHODS: We created mice with SCS using an
      extradural spacer before or after producing SCI and statistically analyzed the
      correlation between the extent of SCS and neurological outcomes. The extent of
      SCS was calculated by micro-computed tomography, and the spinal cord blood flow
      (SCBF) was measured serially with laser Doppler flowmetry. Molecular and
      immunohistochemical examinations were performed to evaluate the
      neovascularization at the site of cord compression. RESULTS: Spacer placement
      (<300 MUm) alone in the control mouse resulted in no neurological deficits. Even
      with spacer placement that caused asymptomatic SCS, the functional recovery after
      SCI was progressively impaired as spacer sizes increased in the mice with SCS co
      occurring with SCI, whereas no significant impact was observed in the mice with
      pre-existing SCS, irrespective of the spacer sizes. The SCBF progressively
      decreased immediately after SCS was produced, but it fully recovered at the later
      time points. Angiogenesis-related genes were upregulated, and neovascular vessels
      were observed after producing the SCS. We found that concurrent SCS resulted in a
      significant reduction and impaired the subsequent recovery of the SCBF, whereas
      pre-existing SCS did not affect the hemodynamics of the spinal cord after SCI.
      CONCLUSION: The dynamic reduction of the SCBF occurring immediately after spinal
      cord compression is a significant factor that impairs the neurological recovery
      after SCI, whereas pre-existing SCS is not always an impediment due to the
      potentially restructured SCBF.

PMID- 22414996
TI  - Nonoperative treatment of occipital condyle fractures: an outcomes review of 32
      fractures.
AB  - STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To evaluate the outcomes
      of patients with occipital condyle fractures (OCFs) treated nonoperatively and
      establish factors associated with neck disability. SUMMARY OF BACKGROUND DATA:
      The majority of OCFs are treated nonoperatively; however, few studies have
      reported long-term functional outcomes of these patients. METHODS: From 1999 to
      2007, 103 patients with OCFs were identified. Of this cohort, 28 patients with 32
      fractures met the inclusion criteria. Fracture and patient characteristics,
      including patient age and sex, Anderson and Montesano fracture type,
      bilaterality, associated head injury, and fracture displacement, were noted. The
      Neck Disability Index (NDI) was calculated at final follow-up. RESULTS: Anderson
      and Montesano type III fractures were the most commonly observed (54%), followed
      by type II (43%). The mean NDI was 14.0, which correlates with mild disability,
      and the NDI headache question showed the highest mean disability score of all
      questions. There was no statistically significant association between NDI scores
      and fracture type, displacement of fracture, sex, bilaterality, or presence of
      head injury. Age was associated with NDI scores, with age range of 40 to 60 years
      having a mean NDI score of 24.3. CONCLUSION: Anderson and Montessano types I, II,
      and III OCFs may be treated nonoperatively in the absence of ligamentous
      instability and concomitant cervical injuries with the expectation of mild neck
      disability regardless of the displacement, bilaterality, sex, or presence of head
      injury. Greater disability may be expected in patients aged between 40 and 60
      years than in other ages.

PMID- 22414999
TI  - Osteoconductive bone graft extenders in posterolateral thoracolumbar spinal
      fusion: a systematic review.
AB  - STUDY DESIGN: A systematic review. OBJECTIVE: To evaluate the efficacy, safety,
      and outcomes of osteoconductive bone graft extenders (BGEs) compared with iliac
      crest bone graft (ICBG) in posterolateral thoracolumbar spinal fusion. SUMMARY OF
      BACKGROUND DATA: ICBG is the current "gold standard" for achieving spinal
      arthrodesis. However, morbidity associated with its harvesting has led to the
      increased use of BGEs. METHODS: An electronic literature search was conducted
      through April 2011 using MEDLINE, EMBASE, CENTRAL, and Cochrane Library. Risk of
      bias and methodological assessment was performed using the Cochrane Risk of Bias
      Tool. Higgins I(2) test was used to assess for heterogeneity. Pooled weighted
      relative risk (RR) ratios were calculated to compare fusion and adverse event
      rates. Weighted standardized mean differences were calculated to compare
      functional outcome and pain scores. RESULTS: Thirteen studies were included
      representing a total of 768 patients. Overall study quality was low (mean
      Cochrane Risk of Bias score, 4.8 out of 12; range, 3-6). Fusion rates were
      comparable between the BGE and ICBG groups (RR, 0.96; 95% confidence interval
      [CI], 0.89-1.03; P = 0.28). Higgins I(2) test (58%) suggested substantial
      heterogeneity in the pooling of studies. The pooled rate of donor site pain in
      the ICBG group was 11.2% (95% CI, 7.4%-15.1%). Reported adverse events, excluding
      donor site pain, were significantly lower in the BGE group (RR, 0.42; 95% CI,
      0.28-0.64; P < 0.0001). Functional outcomes were not significantly different
      between the 2 groups. CONCLUSION: Osteoconductive BGEs combined with local spine
      autograft and/or bone marrow aspirate have comparable fusion rates, similar
      functional outcomes, lower complication rates, and a lower risk of donor site
      pain than ICBG. Caution should be taken in interpreting these findings, given the
      low quality of the studies and the heterogeneity in the results. Randomized
      controlled studies using blinded assessments are required to help elucidate more
      conclusive evidence.

PMID- 22415000
TI  - Early imaging for acute low back pain: one-year health and disability outcomes
      among Washington State workers.
AB  - STUDY DESIGN: A population-based, prospective cohort study. OBJECTIVE: To
      evaluate the association of early imaging and health and disability status 1 year
      following acute low back injury, among a population-based sample of Washington
      State workers' compensation claimants. SUMMARY OF BACKGROUND DATA: Use of early
      diagnostic magnetic resonance imaging (MRI) for low back pain (LBP) contributes
      to increasing health care costs but may not lead to better outcomes than delayed
      imaging. In the worker's compensation system, LBP is common and costly. This
      research examines the association between early MRI among workers with LBP and
      health outcomes (pain intensity, Roland disability score, and 36-Item Short Form
      Health Survey scores) and disability status 1 year after injury. METHODS: This
      nonrandomized prospective cohort study of Washington State workers' compensation
      claimants with nonspecific LBP used administrative claims and interview data.
      Multivariable regression methods were used to estimate change in health outcome
      scores, the relative risk of disability at 1 year, and the rate of recovery 1
      year after injury. RESULTS: Of 1226 participants, 18.6% received early MRI. Most
      (77.9%) had mild/major sprains and 22.1% had radiculopathy. Participants with
      early MRI differed significantly at baseline in pain, function, and psychosocial
      variables. After adjusting for covariates, early imaging was not associated with
      substantial differences in 1-year health outcomes for sprains or radiculopathy.
      For workers with mild/major sprain, early imaging was associated with a 2-fold
      increase in the likelihood of work disability benefits at 1 year (adjusted
      relative risk: 2.03, 95% confidence interval: 1.33-3.11). Early imaging was not
      associated with an increased risk of long-term disability for workers with
      radiculopathy (adjusted relative risk: 1.31, 95% confidence interval: 0.84-2.05).
      For both groups, early MRI was associated with longer disability duration (P <
      0.001). CONCLUSION: Among workers with LBP, early MRI is not associated with
      better health outcomes and is associated with increased likelihood of disability
      and its duration. These associations warrant further testing in a randomized
      controlled trial. Our findings suggest that adherence to evidence-based
      guidelines is an important factor in ensuring that workers receive the highest
      quality care for occupational injuries.

PMID- 22415001
TI  - Comparison of 3-dimensional spinal reconstruction accuracy: biplanar radiographs
      with EOS versus computed tomography.
AB  - STUDY DESIGN: Experimental study for systematic evaluation of 3-dimensional (3D)
      reconstructions from low-dose digital stereoradiography. OBJECTIVE: To assess the
      accuracy of EOS (EOS Imaging, Paris, France) 3-dimensional (3D) reconstructions
      compared with 3D computed tomography (CT) and the effect spine positioning within
      the EOS unit has on reconstruction accuracy. SUMMARY OF BACKGROUND DATA:
      Scoliosis is a 3D deformity, but 3D morphological analyses are still rare. A new
      low-dose radiation digital stereoradiography system (EOS) was previously
      evaluated for intra/interobserver variability, but data are limited for 3D
      reconstruction accuracy. METHODS: Three synthetic scoliotic phantoms (T1-pelvis)
      were scanned in upright position at 0 degrees , +/-5 degrees , and +/-10 degrees 
      of axial rotation within EOS and in supine position using CT. Three-dimensional
      EOS reconstructions were superimposed on corresponding 3D computed tomographic
      reconstructions. Shape, position, and orientation accuracy were assessed for each
      vertebra and the entire spine. Additional routine planer clinical deformity
      measurements were compared: Cobb angle, kyphosis, lordosis, and pelvic incidence.
      RESULTS: Mean EOS vertebral body shape accuracy was 1.1 +/- 0.2 mm (maximum 4.7
      mm), with 95% confidence interval of 1.7 mm. Different anatomical vertebral
      regions were modeled well with root-mean-square (RMS) values from 1.2 to 1.6 mm.
      Position and orientation accuracy of each vertebra were high: RMS offset was 1.2
      mm (maximum 3.7 mm) and RMS axial rotation was 1.9 degrees  (maximum 5.8 degrees
      ). There was no significant difference in each of the analyzed parameters (P >
      0.05) associated with varying the rotational position of the phantoms in EOS
      machine. Planer measurements accuracy was less than 1 degrees  mean difference
      for pelvic incidence, Cobb angle (mean 1.6 degrees /maximum 3.9 degrees ), and
      sagittal kyphosis (mean less than 1 degrees , maximum 4.9 degrees ). CONCLUSION:
      The EOS image acquisition and reconstruction software provides accurate 3D spinal
      representations of scoliotic spinal deformities. The results of this study
      provide spinal deformity surgeons evidence pertaining to this new upright 3D
      imaging technology that may aid in the clinical diagnosis and decision making for
      patients with scoliosis.

PMID- 22415002
TI  - On-chip isotachophoresis for separation of ions and purification of nucleic
      acids.
AB  - Electrokinetic techniques are a staple of microscale applications because of
      their unique ability to perform a variety of fluidic and electrophoretic
      processes in simple, compact systems with no moving parts. Isotachophoresis (ITP)
      is a simple and very robust electrokinetic technique that can achieve million
      fold preconcentration and efficient separation and extraction based on ionic
      mobility. For example, we have demonstrated the application of ITP to separation
      and sensitive detection of unlabeled ionic molecules (e.g. toxins, DNA, rRNA,
      miRNA) with little or no sample preparation and to extraction and purification of
      nucleic acids from complex matrices including cell culture, urine, and blood. ITP
      achieves focusing and separation using an applied electric field and two buffers
      within a fluidic channel system. For anionic analytes, the leading electrolyte
      (LE) buffer is chosen such that its anions have higher effective electrophoretic
      mobility than the anions of the trailing electrolyte (TE) buffer (Effective
      mobility describes the observable drift velocity of an ion and takes into account
      the ionization state of the ion, as described in detail by Persat et al.). After
      establishing an interface between the TE and LE, an electric field is applied
      such that LE ions move away from the region occupied by TE ions. Sample ions of
      intermediate effective mobility race ahead of TE ions but cannot overtake LE
      ions, and so they focus at the LE-TE interface (hereafter called the "ITP
      interface"). Further, the TE and LE form regions of respectively low and high
      conductivity, which establish a steep electric field gradient at the ITP
      interface. This field gradient preconcentrates sample species as they focus.
      Proper choice of TE and LE results in focusing and purification of target species
      from other non-focused species and, eventually, separation and segregation of
      sample species. We here review the physical principles underlying ITP and discuss
      two standard modes of operation: "peak" and "plateau" modes. In peak mode,
      relatively dilute sample ions focus together within overlapping narrow peaks at
      the ITP interface. In plateau mode, more abundant sample ions reach a steady
      state concentration and segregate into adjoining plateau-like zones ordered by
      their effective mobility. Peak and plateau modes arise out of the same underlying
      physics, but represent distinct regimes differentiated by the initial analyte
      concentration and/or the amount of time allotted for sample accumulation. We
      first describe in detail a model peak mode experiment and then demonstrate a peak
      mode assay for the extraction of nucleic acids from E. coli cell culture. We
      conclude by presenting a plateau mode assay, where we use a non-focusing tracer
      (NFT) species to visualize the separation and perform quantitation of amino
      acids.

PMID- 22415003
TI  - Death is associated with complement C3 depletion in cerebrospinal fluid of
      patients with pneumococcal meningitis.
AB  - Pneumococcal meningitis can lead to death or serious neurological sequelae as a
      result of the host inflammatory response. We investigated the association between
      host response protein expression and outcome in patients with pneumococcal
      meningitis. Cerebrospinal fluid (CSF) was obtained from 80 patients with
      pneumococcal meningitis (40 nonsurvivors and 40 survivors) and 10 normal
      controls. Candidate proteins were analyzed for an association with survival.
      Complement C3 levels were 5-fold lower in nonsurvivors than in survivors (P <
      0.05). This C3 reduction was not associated with lower levels in serum,
      indicating a compartmentalized CSF response. Transferrin levels were
      significantly higher in CSF (but not serum) from nonsurvivors than in CSF from
      survivors, suggestive of blood-brain barrier damage. Classical apoptosis proteins
      caspase 3 and apoptosis-inducing factor were not present in CSF. Expression of
      creatine kinase BB in clinically infected CSF suggested neuronal necrosis, but
      there was no clear association between level of expression and clinical outcome.
      Increased blood-brain barrier permeability and complement C3 depletion may have a
      role in determining outcome from bacterial meningitis. Therapeutic use of
      citicoline or caspase inhibitors is unlikely to have beneficial effects in
      patients with meningitis. IMPORTANCE: We previously identified proteins
      associated with clinical outcome in patients diagnosed with pneumococcal
      meningitis in a pilot proteomics study of cerebrospinal fluid (CSF). In this
      article, we have quantitatively assayed specific proteins identified from this
      previous proteomics analysis along with proteins associated with cell death by
      using Western blotting.

PMID- 22415004
TI  - Annexin A5 binds to lipopolysaccharide and reduces its endotoxin activity.
AB  - Annexin A5 (AnxA5) has a high affinity for phosphatidylserine. The protein is
      widely used to detect apoptotic cells because phosphatidylserine, a phospholipid
      that is normally present in the inner leaflets of cytoplasmic membranes, becomes
      translocated to the outer leaflets during programmed cell death. Here we report
      the novel observation that AnxA5 binds to Gram-negative bacteria via the lipid A
      domain of lipopolysaccharide (LPS). Binding of AnxA5 to bacteria was measured
      quantitatively, confirmed by fluorescence microscopy, and found to be inhibited
      by antibodies against lipid A. AnxA5 also bound to purified dot-blotted LPS and
      lipid A. Through ellipsometry, we found that the binding of AnxA5 to purified LPS
      was calcium dependent and rapid and showed a high affinity-characteristics
      similar to those of AnxA5 binding to phosphatidylserine. Initial functional
      studies indicated that AnxA5 can affect LPS activities. AnxA5 inhibited LPS
      mediated gelation in the Limulus amebocyte lysate assay. Incubation of LPS with
      the protein reduced the quantity of tumor necrosis factor alpha (TNF-alpha)
      released by cultured monocytes compared to that released upon incubation with LPS
      alone. Initial in vivo experiments indicated that injection of mice with LPS
      preincubated with AnxA5 produced serum TNF-alpha levels lower than those seen
      after injection of LPS alone. These data demonstrate that AnxA5 binds to LPS and
      open paths to investigation of the potential biological and therapeutic
      implications of this interaction. IMPORTANCE: AnxA5 is highly expressed in cells
      that have a barrier function-including, among others, vascular endothelium,
      placental trophoblasts, and epithelial cells lining bile ducts, renal tubules,
      mammary ducts, and nasal epithelium. The protein has been well characterized for
      its binding to phospholipid bilayers that contain phosphatidylserine. This report
      of a previously unrecognized activity of AnxA5 opens the door to investigation of
      the possibility that this binding may have biological and therapeutic
      ramifications. In view of the tissue expression of the protein, the present
      results suggest the possibility that AnxA5 plays a role in modulating the host
      defense against lipopolysaccharide at these anatomic sites, where cells may
      interface with microorganisms. These results also raise the intriguing
      possibility that AnxA5 or analogous proteins or peptides could provide novel
      approaches to addressing the difficult clinical problem of Gram-negative sepsis.

PMID- 22415005
TI  - A bilayer-couple model of bacterial outer membrane vesicle biogenesis.
AB  - Gram-negative bacteria naturally produce outer membrane vesicles (OMVs) that
      arise through bulging and pinching off of the outer membrane. OMVs have several
      biological functions for bacteria, most notably as trafficking vehicles for
      toxins, antimicrobials, and signaling molecules. While their biological roles are
      now appreciated, the mechanism of OMV formation has not been fully elucidated. We
      recently demonstrated that the signaling molecule 2-heptyl-3-hydroxy-4-quinolone
      (PQS) is required for OMV biogenesis in P. aeruginosa. We hypothesized that PQS
      stimulates OMV formation through direct interaction with the outer leaflet of the
      outer membrane. To test this hypothesis, we employed a red blood cell (RBC) model
      that has been used extensively to study small-molecule-membrane interactions. Our
      results revealed that addition of PQS to RBCs induced membrane curvature,
      resulting in the formation of membrane spicules (spikes), consistent with small
      molecules that are inserted stably into the outer leaflet of the membrane.
      Radiotracer experiments demonstrated that sufficient PQS was inserted into the
      membrane to account for this curvature and that curvature induction was specific
      to PQS structure. These data suggest that a low rate of interleaflet flip-flop
      forces PQS to accumulate in and expand the outer leaflet relative to the inner
      leaflet, thus inducing membrane curvature. In support of PQS-mediated outer
      leaflet expansion, the PQS effect was antagonized by chlorpromazine, a molecule
      known to be preferentially inserted into the inner leaflet. Based on these data,
      we propose a bilayer-couple model to describe P. aeruginosa OMV biogenesis and
      suggest that this is a general mechanism for bacterial OMV formation. IMPORTANCE:
      Despite the ubiquity and importance of outer membrane vesicle (OMV) production in
      Gram-negative bacteria, the molecular details of OMV biogenesis are not fully
      understood. Early experiments showed that 2-heptyl-3-hydroxy-4-quinolone (PQS)
      induces OMV formation through physical interaction with the membrane but did not
      elucidate the mechanism. The present study demonstrates that PQS specifically and
      reversibly promotes blebbing of model membranes dependent upon the same
      properties that are required for OMV formation in P. aeruginosa. These results
      are consistent with a mechanism where expansion of the outer leaflet relative to
      the inner leaflet induces localized membrane curvature. This "bilayer-couple"
      model can account for OMV formation under all conditions and is easily
      generalized to other Gram-negative bacteria. The model therefore raises the
      possibility of a universal paradigm for vesicle production in prokaryotes with
      features strikingly different from what is known in eukaryotes.

PMID- 22415006
TI  - Generation of a novel nucleic acid-based reporter system to detect phenotypic
      susceptibility to antibiotics in Mycobacterium tuberculosis.
AB  - We designed, constructed, and evaluated a prototype novel reporter system
      comprised of two functional cassettes: (i) the SP6 RNA polymerase gene under
      transcriptional control of a promoter active in mycobacteria and (ii) the
      consensus SP6 polymerase promoter that directs expression of an otherwise
      unexpressed sequence. We incorporated the reporter system into a
      mycobacteriophage for delivery into viable Mycobacterium tuberculosis, and
      introduction led to synthesis of an SP6 polymerase-dependent surrogate marker RNA
      that we detected by reverse transcriptase PCR (RT-PCR). The reporter confirmed
      the susceptibility profile of both drug-susceptible and drug-resistant M.
      tuberculosis strains exposed to first-line antitubercular drugs and required as
      little as 16 h of exposure to antibacterial agents targeting bacterial metabolic
      processes to accurately read the reaction. The reporter system translated the
      bacterial phenotype into a language interpretable by rapid and sensitive nucleic
      acid detection. As a phenotypic assay that works only on viable M. tuberculosis,
      it could be used to rapidly assess resistance to any drug, including drugs for
      which the mechanism of resistance is unknown or which result from many potential
      known (and unknown) genetic alterations. IMPORTANCE: The ability to detect
      antibiotic resistance of slow-growing bacteria (i.e., Mycobacterium tuberculosis)
      is hampered by two factors, the time to detection (weeks to months) and the
      resistance mechanism (unknown for many drugs), delaying the appropriate treatment
      of patients with drug-resistant or multidrug-resistant tuberculosis (TB). The
      novel technique described in this article uses a unique surrogate nucleic acid
      marker produced by phage that infects M. tuberculosis to record phenotypic
      antibiotic susceptibility in less than a day.

PMID- 22415007
TI  - Increased Y-chromosome detection by SRY duplexing.
AB  - OBJECTIVE: Determining fetal sex noninvasively is dependent of a robust assay. We
      designed a novel SRY assay and combined it with a SRY assay from literature
      forming a duplex assay with the same fluorescent dye to increase detection of Y
      chromosome at low cell-free fetal DNA or chimeric DNA concentrations. METHODS: We
      analyzed 48 plasma samples from pregnant women in gestational weeks 5-35. Fetal
      sex was determined by DYS14 and SRY. We also compared 2 monoplex SRY assays with
      a SRY duplex assay at low DNA concentrations. RESULTS: The DYS14 assay was more
      sensitive than the SRY assay, but less specific at low cell-free fetal DNA
      concentrations. We obtained a more sensitive duplex SRY assay with the same
      specificity as the 2 monoplex assays. CONCLUSION: The SRY duplex assay improves
      the SRY detection at low DNA concentration.

PMID- 22415008
TI  - Dissociated vertical deviation in congenital fibrosis of the extraocular muscles.

PMID- 22415009
TI  - Aqueous solvation of amphiphilic solutes: concentration and temperature dependent
      study of the ultrafast polarisability relaxation dynamics.
AB  - An understanding of the influence of hydrophilic and hydrophobic interactions on
      the dynamics of solvating water molecules is important in a diverse range of
      phenomena. The polarisability anisotropy relaxation dynamics of aqueous solutions
      of the amphiphiles TBA (t-butyl alcohol) and TMAO (trimethylamine N-oxide) have
      been measured as a function of concentration and temperature. TMAO is shown to
      have a greater effect on the picosecond relaxation dynamics of water than TBA.
      This result is consistent with hydrophilic interactions being mainly responsible
      for the slowing down the polarisability relaxation in aqueous solutions. The room
      temperature Raman spectral densities of the two solutions are remarkably similar
      to that of bulk water, an effect which is tentatively ascribed to the formation
      of nanoscale structure in the solutions, allowing the formation of bulk-like
      water pools. The temperature dependent spectral density of TMAO remains similar
      to that of bulk water at all temperatures, while that for TBA shows a marked
      decrease in the amplitude of the response usually ascribed to a water-water
      stretch with increasing temperature. This is discussed in terms of the
      temperature dependent structure of TBA aggregates in solution.

PMID- 22415010
TI  - Deficiency of glycine N-methyltransferase aggravates atherosclerosis in
      apolipoprotein E-null mice.
AB  - The mechanism underlying the dysregulation of cholesterol metabolism and
      inflammation in atherogenesis is not understood fully. Glycine N
      methyltransferase (GNMT) has been implicated in hepatic lipid metabolism and the
      pathogenesis of liver diseases. However, little is known about the significance
      of GNMT in atherosclerosis. We showed the predominant expression of GNMT in foamy
      macrophages of mouse atherosclerotic aortas. Genetic deletion of GNMT exacerbated
      the hyperlipidemia, inflammation and development of atherosclerosis in
      apolipoprotein E-deficient mice. In addition, ablation of GNMT in macrophages
      aggravated oxidized low-density lipoprotein-mediated cholesterol accumulation in
      macrophage foam cells by downregulating the expression of reverse cholesterol
      transporters including ATP-binding cassette transporters-A1 and G1 and scavenger
      receptor BI. Furthermore, tumor necrosis factor-alpha-induced inflammatory
      response was promoted in GNMT-null macrophages. Collectively, our data suggest
      that GNMT is a crucial regulator in cholesterol metabolism and in inflammation,
      and contributes to the pathogenesis of atherosclerosis. This finding may reveal a
      potential therapeutic target for atherosclerosis.

PMID- 22415011
TI  - Delayed administration of pyroglutamate helix B surface peptide (pHBSP), a novel
      nonerythropoietic analog of erythropoietin, attenuates acute kidney injury.
AB  - In preclinical studies, erythropoietin (EPO) reduces ischemia-reperfusion
      associated tissue injury (for example, stroke, myocardial infarction, acute
      kidney injury, hemorrhagic shock and liver ischemia). It has been proposed that
      the erythropoietic effects of EPO are mediated by the classic EPO receptor
      homodimer, whereas the tissue-protective effects are mediated by a hetero-complex
      between the EPO receptor monomer and the beta-common receptor (termed "tissue
      protective receptor"). Here, we investigate the effects of a novel, selective
      ligand of the tissue-protective receptor (pyroglutamate helix B surface peptide
      [pHBSP]) in a rodent model of acute kidney injury/dysfunction. Administration of
      pHBSP (10 MUg/kg intraperitoneally [i.p.] 6 h into reperfusion) or EPO (1,000
      IU/kg i.p. 4 h into reperfusion) to rats subjected to 30 min ischemia and 48 h
      reperfusion resulted in significant attenuation of renal and tubular dysfunction.
      Both pHBSP and EPO enhanced the phosphorylation of Akt (activation) and glycogen
      synthase kinase 3beta (inhibition) in the rat kidney after ischemia-reperfusion,
      resulting in prevention of the activation of nuclear factor-kappaB (reduction in
      nuclear translocation of p65). Interestingly, the phosphorylation of endothelial
      nitric oxide synthase was enhanced by EPO and, to a much lesser extent, by pHBSP,
      suggesting that the signaling pathways activated by EPO and pHBSP may not be
      identical.

PMID- 22415012
TI  - A CYP26B1 polymorphism enhances retinoic acid catabolism and may aggravate
      atherosclerosis.
AB  - All-trans retinoic acid, controlled by cytochrome P450, family 26 (CYP26)
      enzymes, potentially has beneficial effects in atherosclerosis treatment. This
      study investigates CYP26 subfamily B, polypeptide 1 (CYP26B1) in atherosclerosis
      and the effects of a genetic polymorphism in CYP26B1 on retinoid catabolism. We
      found that CYP26B1 mRNA was induced by retinoic acid in human atherosclerotic
      arteries, and CYP26B1 and the macrophage marker CD68 were colocalized in human
      atherosclerotic lesions. In mice, Cyp26B1 mRNA was higher in atherosclerotic
      arteries than in normal arteries. Databases were queried for nonsynonymous
      CYP26B1 single nucleotide polymorphisms (SNPs) and rs2241057 selected for further
      studies. Constructs of the CYP26B1 variants were created and used for production
      of purified proteins and transfection of macrophagelike cells. The minor variant
      catabolized retinoic acid with significantly higher efficiency, indicating that
      rs2241057 is functional and suggesting reduced retinoid availability in tissues
      with the minor variant. rs2241057 was investigated in a Stockholm Coronary
      Atherosclerosis Risk Factor (SCARF) subgroup. The minor allele was associated
      with slightly larger lesions, as determined by angiography. In summary, this
      study identifies the first CYP26B1 polymorphism that alters CYP26B1 capacity to
      metabolize retinoic acid. CYP26B1 was expressed in macrophage-rich areas of human
      atherosclerotic lesions, induced by retinoic acid and increased in murine
      atherosclerosis. Taken together, the results indicate that CYP26B1 capacity is
      genetically regulated and suggest that local CYP26B1 activity may influence
      atherosclerosis.

PMID- 22415014
TI  - Complex evolution in Arundinarieae (Poaceae: Bambusoideae): incongruence between
      plastid and nuclear GBSSI gene phylogenies.
AB  - The monophyly of tribe Arundinarieae (the temperate woody bamboos) has been
      unequivocally recovered in previous molecular phylogenetic studies. In a recent
      phylogenetic study, 10 major lineages in Arundinarieae were resolved based on
      eight non-coding plastid regions, which conflicted significantly with
      morphological classifications both at the subtribal and generic levels.
      Nevertheless, relationships among and within the 10 lineages remain unclear. In
      order to further unravel the evolutionary history of Arundinarieae, we used the
      nuclear GBSSI gene sequences along with those of eight plastid regions for
      phylogenetic reconstruction, with an emphasis on Chinese species. The results of
      the plastid analyses agreed with previous studies, whereas 13 primary clades
      revealed in the GBSSI phylogeny were better resolved at the generic level than
      the plastid phylogeny. Our analyses also revealed many inconsistencies between
      the plastid DNA and the nuclear GBSSI trees. These results implied that the
      nuclear genome and the plastid genome had different evolutionary trajectories.
      The patterns of incongruence suggested that lack of informative characters,
      incomplete lineage sorting, and/or hybridization (introgression) could be the
      causes. Seven putative hybrid species were hypothesized, four of which are
      discussed in detail on the basis of topological incongruence, chromosome numbers,
      morphology, and distribution patterns, and those taxa probably resulted from
      homoploid hybrid speciation. Overall, our study indicates that the tribe
      Arundinarieae has undergone a complex evolution.

PMID- 22415013
TI  - Diametrically opposite methylome-transcriptome relationships in high- and low-CpG
      promoter genes in postmitotic neural rat tissue.
AB  - DNA methylation can control some CpG-poor genes but unbiased studies have not
      found a consistent genome-wide association with gene activity outside of CpG
      islands or shores possibly due to use of cell lines or limited bioinformatics
      analyses. We performed reduced representation bisulfite sequencing (RRBS) of rat
      dorsal root ganglia encompassing postmitotic primary sensory neurons (n = 5, r >
      0.99; orthogonal validation p < 10(-19)). The rat genome suggested a dichotomy of
      genes previously reported in other mammals: low CpG content (< 3.2%) promoter
      (LCP) genes and high CpG content (>= 3.2%) promoter (HCP) genes. A genome-wide
      integrated methylome-transcriptome analysis showed that LCP genes were markedly
      hypermethylated when repressed, and hypomethylated when active with a 40%
      difference in a broad region at the 5' of the transcription start site (p < 10(
      87) for -6000 bp to -2000 bp, p < 10(-73) for -2000 bp to +2000 bp, no difference
      in gene body p = 0.42). HCP genes had minimal TSS-associated methylation
      regardless of transcription status, but gene body methylation appeared to be lost
      in repressed HCP genes. Therefore, diametrically opposite methylome-transcriptome
      associations characterize LCP and HCP genes in postmitotic neural tissue in vivo.

PMID- 22415015
TI  - Rapid diversification in the North American minnow genus Nocomis.
AB  - Diversification rates among stream fishes are likely governed by geographical
      factors that impact connectivity among and between stream systems. Herein we
      investigate rates of diversification within species of River Chubs, Nocomis, a
      monophyletic group of stream fishes distributed throughout the drainage basins of
      the Mississippi River, Atlantic Slope and Gulf Coast. We used nucleotide
      sequences of two protein-coding nuclear genes (IRBP and rhodopsin) and one
      mitochondrial gene (cytochrome b) to generate a phylogenetic hypothesis of
      population-level relationships within and among species. Results of molecular
      analyses suggest that morphological and meristic treatments of Nocomis have
      underestimated species diversity within the group. Tree-based Bayesian methods
      and diversification statistics were implemented to model the rate of evolutionary
      change along lineages and estimate divergence dates among phylogroups.
      Significantly elevated rates of cladogenesis are observed among coastally
      distributed populations 2-3 million years before present. This period was
      dominated by dramatic sea level fluctuations that suggest a period of climatic
      instability. Climatic instability and other factors may have driven the burst of
      rapid diversification observed in Nocomis. Results generated in this study
      reinforce faunistic and geologic arguments for the hypothesized existence of
      extinct rivers, such as White's River and the Appalachian River.

PMID- 22415016
TI  - Blended learning in paediatric emergency medicine:  preliminary analysis of a
      virtual learning environment.
AB  - OBJECTIVES: Paediatric emergency medicine (PEM) currently faces many competing
      educational challenges. Recent changes to the working patterns have made the
      delivery of effective teaching to trainees extremely difficult. We developed a
      virtual learning environment, on the basis of socioconstructivist principles,
      which allows learning to take place regardless of time or location. The aim was
      to evaluate the effectiveness of a blended e-learning approach for PEM training.
      METHODS: We evaluated the experiences of ST3 trainees in PEM using a multimodal
      approach. We classified and analysed message board discussions over a 6-month
      period to look for evidence of practice change and learning. We conducted
      semistructured qualitative interviews with trainees approximately 5 months after
      they completed the course. RESULTS: Trainees embraced the virtual learning
      environment and had positive experiences of the blended approach to learning.
      Socioconstructivist learning did take place through the use of message boards on
      the virtual learning environment. Despite their initial unfamiliarity with the
      online learning system, the participants found it easy to access and use. The
      participants found the learning relevant and there was an overlap between shop
      floor learning and the online content. Clinical discussion was often led by
      trainees on the forums and these were described as enjoyable and informative.
      CONCLUSION: A blended approach to e-learning in basic PEM is effective and
      enjoyable to trainees.

PMID- 22415018
TI  - Intravenous immunoglobulins modulate neutrophil activation and vascular injury
      through FcgammaRIII and SHP-1.
AB  - RATIONALE: Intravascular neutrophil recruitment and activation are key pathogenic
      factors that contribute to vascular injury. Intravenous immunoglobulin (IVIG) has
      been shown to have a beneficial effect in systemic inflammatory disorders;
      however, the mechanisms underlying IVIG's inhibitory effect on neutrophil
      recruitment and activation are not understood. OBJECTIVE: We studied the
      mechanisms by which IVIG exerts protection from neutrophil-mediated acute
      vascular injury. METHODS AND RESULTS: We examined neutrophil behavior in response
      to IVIG in vivo, using real-time intravital microscopy. We found that an antibody
      that blocks both FcgammaRIII and its inhibitory receptor counterpart,
      FcgammaRIIB, abrogated the inhibitory effect of IVIG on leukocyte recruitment and
      heterotypic red blood cell (RBC) interactions with adherent leukocytes in wild
      type mice. In the context of sickle cell disease, the blockade of both
      FcgammaRIIB and III abrogated the protective effect of IVIG on acute vaso
      occlusive crisis caused by neutrophil recruitment and activation. Analysis of
      FcgammaRIIB- and FcgammaRIII-deficient mice revealed the predominant expression
      of FcgammaRIII on circulating neutrophils. FcgammaRIII mediated IVIG-triggered
      inhibition of leukocyte recruitment, circulating RBC capture, and enhanced Mac-1
      activity, whereas FcgammaRIIB was dispensable. In addition, FcgammaRIII-induced
      IVIG anti-inflammatory activity in neutrophils was mediated by recruitment of Src
      homology 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1). Indeed, the
      protective effect of IVIG on leukocyte recruitment and activation was abrogated
      in SHP-1-mutant mice. CONCLUSIONS: FcgammaRIII, a classic activating receptor,
      has an unexpected inhibitory role on neutrophil adhesion and activation via
      recruitment of SHP-1 in response to IVIG. Our results identify SHP-1 as a
      therapeutic target in neutrophil-mediated vascular injury.

PMID- 22415017
TI  - Revascularization of ischemic skeletal muscle by estrogen-related receptor-gamma.
AB  - RATIONALE: Oxidative myofibers in the skeletal muscles express high levels of
      angiogenic factors, have dense vasculature, and promptly revascularize during
      ischemia. Estrogen-related receptor-gamma (ERRgamma) activates genes that govern
      metabolic and vascular features typical to oxidative myofibers. Therefore,
      ERRgamma-dependent remodeling of the myofibers may promote neoangiogenesis and
      restoration of blood perfusion in skeletal muscle ischemia. OBJECTIVE: To
      investigate the muscle fiber type remodeling by ERRgamma and its role in the
      vascular recovery of ischemic muscle. METHODS AND RESULTS: Using immunohistology,
      we show that skeletal muscle-specific transgenic overexpression of ERRgamma
      increases the proportions of oxidative and densely vascularized type IIA and IIX
      myofibers and decreases glycolytic and less vascularized type IIB myofibers. This
      myofiber remodeling results in a higher basal blood flow in the transgenic
      skeletal muscle. By applying unilateral hind limb ischemia to transgenic and wild
      type mice, we found accelerated revascularization (fluorescent microangiography),
      restoration of blood perfusion (laser Doppler flowmetry), and muscle repair
      (Evans blue dye exclusion) in transgenic compared to wild-type ischemic muscles.
      This ameliorative effect is linked to enhanced neoangiogenesis (CD31 staining and
      microfil perfusion) by ERRgamma. Using cultured muscle cells in which ERRgamma is
      inactivated, we show that the receptor is dispensable for the classical hypoxic
      response of transcriptional upregulation and secretion of vascular endothelial
      growth factor A. Rather, the ameliorative effect of ERRgamma is linked to the
      receptor-mediated increase in oxidative myofibers that inherently express and
      secrete high levels of angiogenic factors. CONCLUSIONS: The ERRgamma is a hypoxia
      independent inducer of neoangiogenesis that can promote reparative
      revascularization.

PMID- 22415019
TI  - Influence of body parameters on gastric bioelectric and biomagnetic fields in a
      realistic volume conductor.
AB  - Electrogastrograms (EGG) and magnetogastrograms (MGG) provide two complementary
      methods for non-invasively recording electric or magnetic fields resulting from
      gastric electrical slow wave activity. It is known that EGG signals are
      relatively weak and difficult to reliably record while magnetic fields are, in
      theory, less attenuated by the low-conductivity fat layers present in the body.
      In this paper, we quantified the effects of fat thickness and conductivity values
      on resultant magnetic and electric fields using anatomically realistic torso
      models and trains of dipole sources reflecting recent experimental results. The
      results showed that when the fat conductivity was increased, there was minimal
      change in both potential and magnetic fields. However, when the fat conductivity
      was reduced, the magnetic fields were largely unchanged, but electric potentials
      had a significant change in patterns and amplitudes. When the thickness of the
      fat layer was increased by 30 mm, the amplitude of the magnetic fields decreased
      10% more than potentials but magnetic field patterns were changed about four
      times less than potentials. The ability to localize the underlying sources from
      the magnetic fields using a surface current density measure was altered by less
      than 2 mm when the fat layer was increased by 30 mm. In summary, results confirm
      that MGG provides a favorable method over EGG when there are uncertain levels of
      fat thickness or conductivity.

PMID- 22415020
TI  - Genetic and clinical heterogeneity in Meniere's disease.

PMID- 22415021
TI  - Effective treatment of rat adjuvant-induced arthritis by celastrol.
AB  - We have previously reported an increase in interleukin (IL)-1beta and IL-17
      levels, and a continuous activation of caspase-1 in early rheumatoid arthritis
      (RA) patients. These results suggest that drugs targeting IL-1beta regulatory
      pathways, in addition to tumor necrosis factor (TNF), may constitute promising
      therapeutic agents in early RA. We have recently used a THP-1 macrophage-like
      cell line to screen 2320 compounds for those that down-regulate both IL-1beta and
      TNF secretion. Celastrol was one of the most promising therapeutic candidates
      identified in that study. Our main goal in the present work was to investigate
      whether administration of celastrol is able to attenuate inflammation in a rat
      model of adjuvant-induced arthritis (AIA). Moreover, since IL-1beta is known to
      play a role in the polarization of Th17 cells, we also investigate whether
      administration of digoxin, a specific inhibitor of Th17 cells polarization, is
      able to attenuate inflammation in the same rat model. We found that celastrol
      administration significantly suppressed joint inflammation. The histological and
      immunohistochemical evaluation revealed that celastrol-treated rats had a normal
      joint structure with complete abrogation of the inflammatory infiltrate and
      cellular proliferation. In contrast, we observed that digoxin administration
      significantly ameliorated inflammation but only if administrated in the early
      phase of disease course (after 4days of disease induction), and it was not
      efficient at inhibiting the infiltration of immune cells within the joint and in
      preventing damage. Thus, our results suggest that celastrol has significant anti
      inflammatory and anti-proliferative properties and can constitute a potential
      anti-inflammatory drug with therapeutic efficacy in the treatment of immune
      mediated inflammatory diseases such as RA. Furthermore, we find that early
      inhibition of Th17 cells polarization ameliorates arthritis but it is not as
      effective as celastrol.

PMID- 22415022
TI  - Vascular endothelial growth factor receptor-2 in macular oedema with retinal vein
      occlusion.
AB  - BACKGROUND: To evaluate the relationships among vitreous fluid levels of soluble
      vascular endothelial growth factor receptor-2 (sVEGFR-2), vascular endothelial
      growth factor (VEGF), and the severity of macular oedema secondary to branch
      retinal vein occlusion (BRVO). METHODS: Twenty-five BRVO patients with macular
      oedema were enrolled. Vitreous fluid samples were obtained during vitreoretinal
      surgery to measure the levels of sVEGFR-2 and VEGF. Macular oedema was examined
      by optical coherence tomography. RESULTS: The vitreous fluid levels of VEGF and
      sVEGFR-2 were significantly correlated with the severity of macular oedema (rho =
      0.54, p = 0.008 and rho = 0.40, p = 0.047, respectively). The sVEGFR-2 * VEGF
      product was also significantly correlated with the severity of macular oedema
      (rho = 0.62, p = 0.003). CONCLUSIONS: The severity of macular oedema was more
      closely associated with sVEGFR-2 * VEGF than sVEGFR-2 or VEGF alone, suggesting
      that macular oedema in BRVO patients may be influenced by both VEGF and sVEGFR-2.

PMID- 22415023
TI  - Microchip electrophoresis with amperometric detection for the study of the
      generation of nitric oxide by NONOate salts.
AB  - Microchip electrophoresis (ME) with electrochemical detection was used to monitor
      nitric oxide (NO) production from diethylammonium (Z)-1-(N,N-diethylamino)diazen
      1-ium-1,2-diolate (DEA/NO) and 1-(hydroxyl-NNO-azoxy)-L-proline disodium salt
      (PROLI/NO). NO was generated through acid hydrolysis of these NONOate salts. The
      products of acid hydrolysis were introduced into a 5-cm separation channel using
      gated injection. The separation was accomplished using reverse polarity and a
      background electrolyte consisting of 10 mM boric acid and 2 mM
      tetradecyltrimethylammonium bromide, pH 11. Electrochemical detection was
      performed using an isolated potentiostat in an in-channel configuration.
      Potentials applied to the working electrode, typically higher than +1.0 V vs.
      Ag/AgCl, allowed the direct detection of nitrite, NO, DEA/NO, and PROLI/NO.
      Baseline resolution was achieved for the separation of PROLI/NO and NO while
      resolution between DEA/NO and NO was poor (1.0 +/- 0.2). Nitrite was present in
      all samples tested.

PMID- 22415024
TI  - Conformational analyses of peptides and proteins by vibrational Raman optical
      activity.
AB  - Recent developments of vibrational Raman optical activity (ROA) spectroscopy
      enabled the detailed analyses of the backbone and side chain conformations of
      peptides and proteins in solution phases. ROA can be used as a powerful
      analytical technique for determining not only the structures of conformers, but
      also their populations even for systems in fast conformational equilibria where
      NMR spectroscopy is difficult to be applied. ROA enabled the monitoring of the
      secondary structures of denatured or unfolded proteins, such as an amyloid fibril
      and its prefibril intermediates.

PMID- 22415025
TI  - Preparation of a sewage sludge laboratory quality control material for butyltin
      compounds and their determination by isotope-dilution mass spectrometry.
AB  - The characterisation of a laboratory quality control material (QCM) for
      dibutyltin (DBT) and tributyltin (TBT) in sewage sludge is described. The
      reference values were determined by the use of two different types of isotope
      dilution mass spectrometry: gas chromatography-mass spectrometry and gas
      chromatography-inductively coupled plasma mass spectrometry. To avoid possible
      analytical errors such as non-quantitative extraction and species degradation
      during sample preparation, different extraction methods were tested (microwave-
      and ultrasound-assisted extraction and mechanical stirring). The reference values
      were based on the unweighted means of results from the homogenisation and
      characterisation studies. The reference values obtained were 1,553 +/- 87 and 534
      +/- 38 ng Sn g(-1) for DBT and TBT, respectively. In the uncertainty budget
      estimation, the sample inhomogeneity and between-method imprecision were taken
      into account. The concentrations of DBT and TBT in QCM are similar to those in
      the harbour sediment certified reference material PACS-2. Likewise, the levels of
      DBT and TBT are in the range of these compounds normally present in sewage sludge
      worldwide. In the future, the QCM will be used for an intercomparison study on
      DBT and TBT in sewage sludge, and as a day-to-day QCM during studies concerning
      the application of sewage sludge as an additive to artificial soil or as a raw
      material in civil engineering construction.

PMID- 22415026
TI  - Spatiotemporal alteration of phospholipids and prostaglandins in a rat model of
      spinal cord injury.
AB  - We determined quantitative and qualitative alterations in lipids during the
      occurrence and progression of spinal cord injury (SCI) in rats to identify
      potential clinical indicators of SCI pathology. Imaging mass spectrometry (IMS)
      was used to visualize twelve molecular species of phosphatidylcholine (PC) on
      thin slices of spinal cord with SCI. In addition, twelve species of phospholipids
      and five species of prostaglandins (PGs) were quantified by liquid chromatography
      electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) of lipid extracts
      from control/injured spinal cords. Unique distribution patterns were observed for
      phospholipids with different fatty acid compositions, and distinct dynamic
      changes were seen in both their amounts and their distributions in tissue as
      tissue damage resulting from SCI progressed. In particular, PCs containing
      docosahexaenoic acid localized to the large nucleus in the anterior horn region
      at one day post-SCI and rapidly decreased thereafter. In contrast, PCs containing
      arachidonic acid (AA-PCs) were normally found in the posterior horn region and
      were intensely and temporarily elevated one week after SCI.
      Lysophosphatidylcholines (LPCs) also increased at the same SCI stage and in
      regions with elevated AA-PCs, indicating the release of AA and the production of
      PGs. Moreover, LC-ESI-MS/MS analysis of lipid extracts from the spinal cord
      tissue at the impact site demonstrated a peak in PGE2 that reflected the
      elevation/reduction pattern of AA-PCs and LPC. Although further investigation is
      required, we suggest that invasive immune cells that penetrated from the impaired
      blood-brain barrier at 1-2 weeks post-SCI may have produced LPCs, released AA
      from AA-PCs, and produced PGs in SCI tissue at sites enriched in AA-PCs/LPC.

PMID- 22415028
TI  - Showcase for endocrine disruption.

PMID- 22415029
TI  - The immninent dawn of SPRMs in obstetrics and gynecology.
AB  - Selective progesterone receptor modulators (SPRMs) have been developed since the
      late 70s when mifepristone was first described. They act through nuclear
      progesterone receptors and can have agonist or mixed agonist antagonist actions
      depending on the cell and tissue. Mifepristone has unique major antagonist
      properties allowing its use for pregnancy termination. Ulipristal acetate has
      been marketed in 2009 for emergency contraception and has been recently approved
      for preoperative myoma treatment. Further perspectives for SPRMs use include long
      term estrogen free contraception, endometriosis treatment. However long term
      applications will be possible only after confirmation of endometrial safety.

PMID- 22415030
TI  - Tibiofibular screw fixation for syndesmotic ruptures: a biomechanical analysis.
AB  - The mechanisms of injuries to the tibiofibular syndesmosis include isolated
      rupture and rupture in combination with ankle fractures. Current concepts of
      surgical treatment are fixation using bioabsorbable screws, syndesmotic stapling,
      syndesmotic hooks, and the widely used screw fixation. Postoperative care
      utilises passive motion of the ankle joint either with or without axial weight
      bearing. The aim of our investigation was to quantify the motion of the mortise
      during axial load. Therefore, photoelastic tests, on the one hand, and
      biomechanical tests of cadaveric specimens, on the other, using axial loads of up
      to 2,000 N were used. Our photoelastic investigations showed force distribution
      through the screw into the cranial and caudal parts of the distal fibula.
      Biomechanical testing showed a progressive dehiscence in both ruptured and
      fixated specimens up to 2.89 (ruptured) and 2.42 mm (despite screw). Our findings
      strongly suggest a concept of partial weight-bearing at most to support
      regeneration of scar tissue and to prevent the appearance of instability in the
      ankle joint.

PMID- 22415027
TI  - The peroxisome: an update on mysteries.
AB  - Peroxisomes contribute to several crucial metabolic processes such as beta
      oxidation of fatty acids, biosynthesis of ether phospholipids and metabolism of
      reactive oxygen species, which render them indispensable to human health and
      development. Peroxisomes are highly dynamic organelles that rapidly assemble,
      multiply and degrade in response to metabolic needs. In recent years, the
      interest in peroxisomes and their physiological functions has significantly
      increased. This review intends to highlight recent discoveries and trends in
      peroxisome research, and represents an update as well as a continuation of a
      former review article. Novel exciting findings on the biological functions,
      biogenesis, formation and degradation of peroxisomes, on peroxisomal dynamics and
      division, as well as on the interaction and cross-talk of peroxisomes with other
      subcellular compartments are addressed. Furthermore, recent findings on the role
      of peroxisomes in the brain are discussed.

PMID- 22415031
TI  - Glass wool filters for concentrating waterborne viruses and agricultural zoonotic
      pathogens.
AB  - The key first step in evaluating pathogen levels in suspected contaminated water
      is concentration. Concentration methods tend to be specific for a particular
      pathogen group, for example US Environmental Protection Agency Method 1623 for
      Giardia and Cryptosporidium, which means multiple methods are required if the
      sampling program is targeting more than one pathogen group. Another drawback of
      current methods is the equipment can be complicated and expensive, for example
      the VIRADEL method with the 1MDS cartridge filter for concentrating viruses. In
      this article we describe how to construct glass wool filters for concentrating
      waterborne pathogens. After filter elution, the concentrate is amenable to a
      second concentration step, such as centrifugation, followed by pathogen detection
      and enumeration by cultural or molecular methods. The filters have several
      advantages. Construction is easy and the filters can be built to any size for
      meeting specific sampling requirements. The filter parts are inexpensive, making
      it possible to collect a large number of samples without severely impacting a
      project budget. Large sample volumes (100s to 1,000s L) can be concentrated
      depending on the rate of clogging from sample turbidity. The filters are highly
      portable and with minimal equipment, such as a pump and flow meter, they can be
      implemented in the field for sampling finished drinking water, surface water,
      groundwater, and agricultural runoff. Lastly, glass wool filtration is effective
      for concentrating a variety of pathogen types so only one method is necessary.
      Here we report on filter effectiveness in concentrating waterborne human
      enterovirus, Salmonella enterica, Cryptosporidium parvum, and avian influenza
      virus.

PMID- 22415033
TI  - Re: "Use of penicillin and other antibiotics and risk of multiple sclerosis: a
      population-based case-control study".

PMID- 22415032
TI  - Cardiovascular epidemiology in a changing world--challenges to investigators and
      the National Heart, Lung, and Blood Institute.
AB  - Over the past 60 years, revolutionary discoveries made by epidemiologists have
      contributed to marked declines in cardiovascular disease morbidity and mortality.
      Now, in an era of increasingly constrained resources, researchers in
      cardiovascular epidemiology face a number of challenges that call for novel,
      paradigm-shifting approaches. In this paper, the authors pose to the community 4
      critical questions: 1) How can we avoid wasting resources on studies that provide
      little incremental knowledge? 2) How can we assure that we direct our resources
      as economically as possible towards innovative science? 3) How can we be nimble,
      responding quickly to new opportunities? 4) How can we identify prospectively the
      most meritorious research questions? Senior program staff at the National Heart,
      Lung, and Blood Institute invite the epidemiology community to join them in an
      ongoing Web-based blog conversation so that together we might develop novel
      approaches that will facilitate the next generation of high-impact discoveries.

PMID- 22415034
TI  - Re: "Use of penicillin and other antibiotics and risk of multiple sclerosis: a
      population-based case-control study".

PMID- 22415035
TI  - Neoadjuvant use of sunitinib in locally advanced GIST with intolerance to
      imatinib.
AB  - Gastrointestinal stromal tumors (GIST) arise from precursor cells in the
      myenteric plexus and comprise the most common mesenchymal tumors of the
      gastrointestinal tract. Surgical resection is the mainstay of therapy for
      localized disease. Recurrent, unresectable, and metastatic tumors are associated
      with a poor prognosis given their resistance to conventional chemotherapy and
      radiation. Advances in the understanding of molecular pathophysiology of GIST and
      the use of targeted small-molecule therapies have resulted in dramatic increases
      in survival. Preliminary data have demonstrated benefits in using imatinib in a
      neoadjuvant setting; however, there are no studies to date analyzing the use of
      neoadjuvant sunitinib in primary advanced GIST. Here we present the case of a
      patient with locally advanced primary GIST who developed severe toxicity on
      imatinib therapy and was successfully treated with sunitinib in the neoadjuvant
      setting to achieve complete surgical resection.

PMID- 22415036
TI  - Heritability of dietary food intake patterns.
AB  - The quality and quantity of food intake affect body weight, but little is known
      about the genetics of such human dietary intake patterns in relation to the
      genetics of BMI. We aimed to estimate the heritability of dietary intake patterns
      and genetic correlation with BMI in participants of the Erasmus Rucphen Family
      study. The study included 1,690 individuals (42 % men; age range, 19-92), of whom
      41.4 % were overweight and 15.9 % were obese. Self-report questionnaires were
      used to assess the number of days (0-7) on which participants consumed
      vegetables, fruit, fruit juice, fish, unhealthy snacks, fastfood, and soft
      drinks. Principal component analysis was applied to examine the correlations
      between the questionnaire items and to generate dietary intake pattern scores.
      Heritability and the shared genetic and shared non-genetic (environmental)
      correlations were estimated using the family structure of the cohort. Principal
      component analysis suggested that the questionnaire items could be grouped in a
      healthy and unhealthy dietary intake pattern, explaining 22 and 18 % of the
      phenotypic variance, respectively. The dietary intake patterns had a heritability
      of 0.32 for the healthy and 0.27 for the unhealthy pattern. Genetic correlations
      between the dietary intake patterns and BMI were not significant, but we found a
      significant environmental correlation between the unhealthy dietary intake
      pattern and BMI. Specific dietary intake patterns are associated with the risk of
      obesity and are heritable traits. The genetic factors that determine specific
      dietary intake patterns do not significantly overlap with the genetic factors
      that determine BMI. 

PMID- 22415037
TI  - Measurement and validation of the nature of salivary adiponectin.
AB  - Adiponectin (Ad) is an adipocyte-derived hormone that plays an essential role in
      regulating insulin sensitivity, inflammation, and atherogenesis. Levels of some
      hormones in saliva change in a fashion similar to that in plasma in response to a
      disease or physiological condition. Since saliva is an easy to obtain biological
      fluid, measurements of salivary hormonal changes are preferred in diagnoses and
      treatments. Therefore, it was of interest to examine the nature of salivary Ad.
      While there have been two publications in the literature reporting presence of Ad
      in human saliva, the nature of salivary Ad has not been characterized. To this
      end, we investigated the effect of sample dilution on the measurement of Ad in
      saliva. To our surprise, we observed an increase in measurable level of Ad in
      saliva on sample dilution. One explanation for this paradoxical observation may
      be the presence of inhibitor(s) of Ad/anti-Ad binding in saliva that following
      dilution relieves the inhibitory effect. Working with this hypothesis, we were
      able to demonstrate the presence of an inhibitor in saliva that co-eluted with
      the dimeric form of Ad and was capable of inhibiting Ad assay. The presence of
      such inhibitor(s) may lead to underestimation of Ad in saliva. 

PMID- 22415038
TI  - A systematic molecular simulation study of ionic liquid surfaces using intrinsic
      analysis methods.
AB  - In this paper, we apply novel intrinsic analysis methods, coupled with bivariate
      orientation analysis, to obtain a detailed picture of the molecular-level
      structure of ionic liquid surfaces. We observe pronounced layering at the
      interface, alternating non-polar with ionic regions. The outermost regions of the
      surface are populated by alkyl chains, which are followed by a dense and tightly
      packed layer formed of oppositely charged ionic moieties. We then systematically
      change the cation chain length, the anion size, the temperature and the molecular
      model, to examine the effect of each of these parameters on the interfacial
      structure. Increasing the cation chain length promotes orientations in which the
      chain is pointing into the vapor, thus increasing the coverage of the surface
      with alkyl groups. Larger anions promote a disruption of the dense ionic layer,
      increasing the orientational freedom of cations and increasing the amount of free
      space. The temperature had a relatively small effect on the surface structure,
      while the effect of the choice of molecular model was clearly significant,
      particularly on the orientational preferences at the interface. Our study
      demonstrates the usefulness of molecular simulation methods in the design of
      ionic liquids to suit particular applications.

PMID- 22415039
TI  - Assessment of sleep quality in adolescents with temporomandibular disorders.
AB  - OBJECTIVES: To determine the frequency of temporomandibular disorders (TMDs) and
      investigate their relationship with sleep quality in 18 and 19-year-old
      adolescents. METHODS: Cross-sectional design; dysfunctions were diagnosed using
      the Research Diagnostic Criteria for Temporomandibular Disorders and sleep was
      assessed using the Pittsburgh Sleep Quality Index in 200 students. Data were
      analyzed by frequency distribution and using the chi-square test and Student's t
      test. RESULTS: 35.5% of the adolescents had dysfunctions. The mean total score of
      adolescents with dysfunctions was 7.34 and 4.76 for adolescents without
      dysfunctions (p < 0.001). 82% of the participants were free from dysfunctions.
      17% of those with dysfunctions had good sleep quality. CONCLUSIONS: The frequency
      of dysfunctions was elevated and dysfunctions were associated with poor sleep
      quality. The study design does not allow it to be determined whether poor sleep
      quality is a cause or a consequence of TMDs, which can be elucidated in future
      studies.

PMID- 22415040
TI  - Retrieving backbone string neighbors provides insights into structural modeling
      of membrane proteins.
AB  - Identification of protein structural neighbors to a query is fundamental in
      structure and function prediction. Here we present BS-align, a systematic method
      to retrieve backbone string neighbors from primary sequences as templates for
      protein modeling. The backbone conformation of a protein is represented by the
      backbone string, as defined in Ramachandran space. The backbone string of a query
      can be accurately predicted by two innovative technologies: a knowledge-driven
      sequence alignment and encoding of a backbone string element profile. Then, the
      predicted backbone string is employed to align against a backbone string database
      and retrieve a set of backbone string neighbors. The backbone string neighbors
      were shown to be close to native structures of query proteins. BS-align was
      successfully employed to predict models of 10 membrane proteins with lengths
      ranging between 229 and 595 residues, and whose high-resolution structural
      determinations were difficult to elucidate both by experiment and prediction. The
      obtained TM-scores and root mean square deviations of the models confirmed that
      the models based on the backbone string neighbors retrieved by the BS-align were
      very close to the native membrane structures although the query and the neighbor
      shared a very low sequence identity. The backbone string system represents a new
      road for the prediction of protein structure from sequence, and suggests that the
      similarity of the backbone string would be more informative than describing a
      protein as belonging to a fold.

PMID- 22415041
TI  - Phase-dependent synaptic changes in the hippocampal CA1 field underlying
      extinction processes in freely moving rats.
AB  - Recent studies focus on the functional significance of a novel form of synaptic
      plasticity, low-frequency stimulation (LFS)-induced synaptic potentiation in the
      hippocampal CA1 area. In the present study, we elucidated dynamic changes in
      synaptic function in the CA1 field during extinction processes associated with
      context-dependent fear memory in freely moving rats, with a focus on LFS-induced
      synaptic plasticity. Synaptic transmission in the CA1 field was transiently
      depressed during each extinction trial, but synaptic efficacy was gradually
      enhanced by repeated extinction trials, accompanied by decreases in freezing. On
      the day following the extinction training, synaptic transmission did not show
      further changes during extinction retrieval, suggesting that the hippocampal
      synaptic transmission that underlies extinction processes changes in a phase
      dependent manner. The synaptic potentiation produced by extinction training was
      mimicked by synaptic changes induced by LFS (0.5 Hz) in the group that previously
      received footshock conditioning. Furthermore, the expression of freezing during
      re-exposure to footshock box was significantly reduced in the LFS application
      group in a manner similar to the extinction group. These results suggest that LFS
      induced synaptic plasticity may be associated with the extinction processes that
      underlie context-dependent fear memory. This hypothesis was supported by the fact
      that synaptic potentiation induced by extinction training did not occur in a
      juvenile stress model that exhibited extinction deficits. Given the similarity
      between these electrophysiological and behavioral data, LFS-induced synaptic
      plasticity may be related to extinction learning, with some aspects of neuronal
      oscillations, during the acquisition and/or consolidation of extinction memory.

PMID- 22415042
TI  - Modified endoscopic maxillary medial sinusotomy for sinonasal inverted papilloma
      with attachment to the anterior medial wall of maxillary sinus.
AB  - OBJECTIVES: The endoscopic management of inverted papilloma (IP) has gained in
      popularity over the last 15 years. However, the appropriate management of lesions
      involving the anterior medial wall of the maxillary sinus still has to be
      determined. METHODS: We performed a retrospective review of the surgical results
      for patients with IP attached to the anterior medial wall of the maxillary sinus
      in the Otolaryngology, Head and Neck Surgery Department, Beijing TongRen
      Hospital. The tumors were removed by using our surgical technique of modified
      endoscopic maxillary medial sinusotomy, which was defined as an extended
      endoscopic medial maxillectomy with preservation of the nasolacrimal duct and
      inferior turbinate. Sinus endoscopy was used to screen for disease after
      endoscopic resection and the clinical outcomes were analyzed. RESULTS: A total of
      7 patients (4 males and 3 females) were identified. Pre- and postoperative
      pathological examinations revealed inverted papilloma as the diagnosis. All
      tumors were defined as Krouse III lesions. There were no complications recorded
      as a result of surgery. All patients remain disease free with a mean follow-up of
      35.7 months (range 20-68 months). CONCLUSION: Sinonasal IP with attachment to the
      anterior medial portion of the maxillary sinus can be treated successfully using
      modified endoscopic maxillary medial sinusotomy with preservation of the
      nasolacrimal duct and inferior turbinate.

PMID- 22415043
TI  - The root as a drill: an ethylene-auxin interaction facilitates root penetration
      in soil.
AB  - Plant roots forage the soil for water and nutrients and overcome the soil's
      physical compactness. Roots are endowed with a mechanism that allows them to
      penetrate and grow in dense media such as soil. However, the molecular mechanisms
      underlying this process are still poorly understood. The nature of the media in
      which roots grow adds to the difficulty to in situ analyze the mechanisms
      underlying root penetration. Inhibition of ethylene perception by application of
      1-methyl cyclopropene (1-MCP) to tomato seedlings nearly abolished the root
      penetration in Soilrite. The reversal of this process by auxin indicated
      operation of an auxin-ethylene signaling pathway in the regulation of root
      penetration. The tomato pct1-2 mutant that exhibits an enhanced polar transport
      of auxin required higher doses of 1-MCP to inhibit root penetration, indicating a
      pivotal role of auxin transport in this process. In this update we provide a
      brief review of our current understanding of molecular processes underlying root
      penetration in higher plants.

PMID- 22415045
TI  - Complex regulation of an R gene SNC1 revealed by auto-immune mutants.
AB  - Plants have evolved resistance (R) proteins to detect pathogen effectors and
      trigger plant defense responses in the so named effector-triggered immunity
      (ETI). R proteins are under negative regulation in plants as upregulated
      activation of R protein is detrimental to plant growth. Autoimmune mutants have
      been instrumental in understanding the fine tuning of plant defense responses.
      Recently, a number of such mutants have been molecularly characterized, and some
      of them result from over-activation of SNC1, a TIR-NBS-LRR type of R protein.
      Studies of these mutants revealed a complex negative regulation of SNC1 activity
      from transcriptional to post-translational regulation. Here, we summarize studies
      on these SNC1-dependent auto-immune mutants and discuss the fine regulation of R
      proteins in plant immunity.

PMID- 22415044
TI  - Identification of miRNAs in sorghum by using bioinformatics approach.
AB  - MicroRNAs (miRNAs) regulate gene expression mainly by post-transcriptional gene
      silencing (PTGS) and in some cases by transcriptional genes silencing (TGS).
      miRNAs play critical roles in developmental processes, nutrient homeostasis,
      abiotic stress and pathogen responses of plants. In contrast to the large number
      of miRNAs predicted in cereal model plant rice, only 148 miRNAs were predicted in
      sorghum till date (miRBase release 17). This suggested that miRNAs identified in
      sorghum is far from saturation. Hence, we developed a bioinformatics pipeline
      using an in-house PERL script and publicly available structure prediction tools
      to identify miRNAs and their target genes from publically available Expressed
      Sequence Tags (EST) and Genomic Survey Sequence (GSS). About 1379 known and
      unique plant miRNAs from 33 different crops were used to predict new miRNAs in
      sorghum. We identified 31 new miRNAs belonging to 10 different miRNA families. We
      predicted 72 potential target genes for 31 miRNAs, and most of these target genes
      are predicted to be involved in plant growth and development.These newly
      identified miRNAs add to the growing database of miRNA and lay the foundation for
      further understanding of miRNA function in sorghum plant development.

PMID- 22415046
TI  - Mechanisms for calcium sensing receptor-regulated stomatal closure in response to
      the extracellular calcium signal.
AB  - In Arabidopsis, extracellular calcium (Ca2+(o)) promotes intracellular calcium
      (Ca2+(i)) transients and stomatal closure, which has been found to be regulated
      by the calcium sensing receptor (CAS). However, the detailed pathways for
      transducting the Ca2+(o) signal by CAS are still unclear. We found that nitric
      oxide (NO) and the hydrogen peroxide (H2O2) accumulated in the guard cell
      chloroplast were the two elements that act downstream of the CAS signaling and
      trigger the stomatal closure by prolonging Ca2+(i) transients. Here we provide
      more commentary on CAS-regulated H2O2 generation from chloroplast and Ca2+(i)
      transients in response to Ca2+(o), as well as other potential mechanisms that may
      be involved in the CAS signaling pathway.

PMID- 22415047
TI  - Role of H2O2 in pea seed germination.
AB  - The imbibition of pea seeds with hydrogen peroxide H2O2 increased the germination
      as well as the seedling growth, producing an invigoration of the seeds. We
      propose that H2O2 could acts as signaling molecule in the beginning of seed
      germination involving specific changes at proteomic, transcriptomic and hormonal
      levels. These findings have practical implication in the context of seed priming
      technologies to invigorate low vigour seeds.

PMID- 22415048
TI  - The ABA-INSENSITIVE-4 (ABI4) transcription factor links redox, hormone and sugar
      signaling pathways.
AB  - The cellular reduction-oxidation (redox) hub processes information from
      metabolism and the environment and so regulates plant growth and defense through
      integration with the hormone signaling network. One key pathway of redox control
      involves interactions with ABSCISIC ACID (ABA). Accumulating evidence suggests
      that the ABA-INSENSITIVE-4 (ABI4) transcription factor plays a key role in
      transmitting information concerning the abundance of ascorbate and hence the
      ability of cells to buffer oxidative challenges. ABI4 is required for the
      ascorbate-dependent control of growth, a process that involves enhancement of
      salicylic acid (SA) signaling and inhibition of jasmonic acid (JA) signaling
      pathways. Low redox buffering capacity reinforces SA- JA- interactions through
      the mediation of ABA and ABI4 to fine-tune plant growth and defense in relation
      to metabolic cues and environmental challenges. Moreover, ABI4-mediated pathways
      of sugar sensitivity are also responsive to the abundance of ascorbate, providing
      evidence of overlap between redox and sugar signaling pathways.

PMID- 22415049
TI  - Plastid DNA in the nucleus: new genes for old.
AB  - Nuclear genomes of eukaryotes are bombarded by a continuous deluge of organellar
      DNA which contributes significantly to eukaryote evolution. Here, we present a
      new PCR-based method that allows the specific amplification of nuclear integrants
      of organellar DNA (norgs) by exploiting recent deletions present in organellar
      genome sequences. We have used this method to amplify nuclear integrants of
      plastid DNA (nupts) from the nuclear genomes of several Nicotiana species and to
      study the evolutionary forces acting upon these sequences. The role of nupts in
      endosymbiotic evolution and the different genetic factors influencing the time
      available for a chloroplastic gene to be functionally relocated in the nucleus
      are discussed.

PMID- 22415050
TI  - Experimental and statistical post-validation of positive example EST sequences
      carrying peroxisome targeting signals type 1 (PTS1).
AB  - We recently developed the first algorithms specifically for plants to predict
      proteins carrying peroxisome targeting signals type 1 (PTS1) from genome
      sequences. As validated experimentally, the prediction methods are able to
      correctly predict unknown peroxisomal Arabidopsis proteins and to infer novel
      PTS1 tripeptides. The high prediction performance is primarily determined by the
      large number and sequence diversity of the underlying positive example sequences,
      which mainly derived from EST databases. However, a few constructs remained
      cytosolic in experimental validation studies, indicating sequencing errors in
      some ESTs. To identify erroneous sequences, we validated subcellular targeting of
      additional positive example sequences in the present study. Moreover, we analyzed
      the distribution of prediction scores separately for each orthologous group of
      PTS1 proteins, which generally resembled normal distributions with group-specific
      mean values. The cytosolic sequences commonly represented outliers of low
      prediction scores and were located at the very tail of a fitted normal
      distribution. Three statistical methods for identifying outliers were compared in
      terms of sensitivity and specificity." Their combined application allows
      elimination of erroneous ESTs from positive example data sets. This new post
      validation method will further improve the prediction accuracy of both PTS1 and
      PTS2 protein prediction models for plants, fungi, and mammals.

PMID- 22415051
TI  - Primary lung transplantation after bridge with extracorporeal membrane
      oxygenation:  a plea for a shift in our paradigms for indications.
AB  - BACKGROUND: The introduction of the lung allocation score has brought lung
      transplantation (LTX) of patients on extracorporeal membrane oxygenation (ECMO)
      bridge into the focus of interest. We reviewed our institutional experience with
      ECMO as a bridge to LTX. METHODS: Between 1998 and 2011, 38 patients (median age
      30.1 years, range 13-66 years) underwent ECMO support with intention to bridge to
      primary LTX. The underlying diagnosis was cystic fibrosis (n=17), pulmonary
      hypertension (n=4), idiopathic pulmonary fibrosis (n=9), adult respiratory
      distress syndrome (n=4), hemosiderosis (n=1), bronchiolitis obliterans (n=1),
      sarcoidosis (n=1), and bronchiectasis (n=1). The type of extracorporeal bridge
      was venovenous (n=18), venoarterial (n=15), interventional lung assist (n=1), or
      a stepwise combination of them (n=4). The median bridging time was 5.5 days
      (range 1-63) days. The type of transplantation was double LTX (n=7), size-reduced
      double LTX (n=8), lobar LTX (n=16), split LTX (n=2), and lobar LTX after ex vivo
      lung perfusion (n=1). RESULTS: Four patients died before transplantation. Thirty
      four patients underwent LTX, of them eight patients died in the hospital after a
      median stay of 24.5 days (range 1-180 days). Twenty-six patients left the
      hospital and returned to normal life (median hospital stay=47.5 days; range 21-90
      days). The 1-, 3-, and 5-year survival for all transplanted patients was 60%,
      60%, and 48%, respectively. The 1-, 3-, and 5-year survival conditional on 3
      month survival for patients bridged with ECMO to LTX (78%, 78%, and 63%) was not
      worse than for other LTX patients within the same period of time (90%, 80%, and
      72%, respectively, P=0.09, 0.505, and 0.344). CONCLUSION: Transplantation of
      patients bridged on ECMO to LTX is feasible and results in acceptable outcome.

PMID- 22415053
TI  - Initiation of ventricular contraction as reflected in the aortic pressure
      waveform.
AB  - Prior to aortic valve opening, aortic pressure is perturbed by ventricular
      contraction. The onset of this pressure perturbation coincides with the onset of
      the left ventricular (LV) isovolumic contraction, and hence will be referred to
      as the start of the arterially detected isovolumic contraction (AIC(start)). In
      the present study we test the hypothesis that the pressure perturbation indeed
      has a cardiac origin. In ten Yorkshire-Landrace swine, waveform intensity
      analysis demonstrated that AIC(start) was followed by a positive intensity wave
      (0.3 * 10(5) +/- 0.3 * 10(5) W (m(2) s(2))(-1)). Timing analysis of LV and aortic
      pressure waveform showed that AIC(start) was preceded by a LV pressure
      perturbation (3.8 +/- 1.8 ms, p < 0.001). These novel cardiac timing and aortic
      wave intensity findings reveal the cardiac origin of the pressure perturbation.
      In 15 Yorkshire-Landrace swine, myocardial motion analysis showed a significantly
      higher rate of segment shortening during the first part of the LV pressure
      perturbation. Therefore, both the LV and aortic pressure perturbation are most
      likely caused by the early phase of myocardial contraction, which also causes
      mitral valve closure. Consequently, AIC(start) is useful in the determination of
      the isovolumic contraction period, a well-known marker to quantify cardiac
      dysfunction.

PMID- 22415054
TI  - 'Porcelain kidney': case report and review of the literature.
AB  - A rare case of pan-subepithelial dystrophic calcium deposition and bone marrow
      formation in hydronephrosis secondary to obstructive urolithiasis is reported and
      discussed. An elderly gentleman presented with accelerated hypertension, a
      nonfunctioning left kidney secondary to obstructive nephrolithiasis with
      additional pancalyceal calcification. His left retroperitoneoscopic nephrectomy
      specimen revealed sterile hydronephrosis secondary to an impacted ureteropelvic
      junction stone and pan-subepithelial fibrocalcific lamellar deposition. Special
      stains confirmed end-stage renal disease with chronic pyelonephritis with
      subepithelial dystrophic calcium deposition and evidence of bone marrow
      formation.

PMID- 22415052
TI  - Computational simulations of hemodynamic changes within thoracic, coronary, and
      cerebral arteries following early wall remodeling in response to distal aortic
      coarctation.
AB  - Mounting evidence suggests that the pulsatile character of blood pressure and
      flow within large arteries plays a particularly important role as a mechano
      biological stimulus for wall growth and remodeling. Nevertheless, understanding
      better the highly coupled interactions between evolving wall geometry, structure,
      and properties and the hemodynamics will require significantly more experimental
      data. Computational fluid-solid-growth models promise to aid in the design and
      interpretation of such experiments and to identify candidate mechanobiological
      mechanisms for the observed arterial adaptations. Motivated by recent aortic
      coarctation models in animals, we used a computational fluid-solid interaction
      model to study possible local and systemic effects on the hemodynamics within the
      thoracic aorta and coronary, carotid, and cerebral arteries due to a distal
      aortic coarctation and subsequent spatial variations in wall adaptation. In
      particular, we studied an initial stage of acute cardiac compensation (i.e.,
      maintenance of cardiac output) followed by early arterial wall remodeling (i.e.,
      spatially varying wall thickening and stiffening). Results suggested, for
      example, that while coarctation increased both the mean and pulse pressure in the
      proximal vessels, the locations nearest to the coarctation experienced the
      greatest changes in pulse pressure. In addition, after introducing a spatially
      varying wall adaptation, pressure, left ventricular work, and wave speed all
      increased. Finally, vessel wall strain similarly experienced spatial variations
      consistent with the degree of vascular wall adaptation.

PMID- 22415056
TI  - HER-2 in breast cancer: a puzzle's piece!

PMID- 22415057
TI  - Use of fluorescence in situ hybridization to distinguish metastatic uveal from
      cutaneous melanoma.
AB  - Metastatic lesions of malignant melanoma can on occasion be difficult to classify
      with regard to the primary site of origin. Given the lack of specificity of light
      microscopic features, ancillary studies are needed. In this study, the authors
      explored the possibility of distinguishing metastatic tumors derived from uveal
      primaries from those known to have originated from a cutaneous melanoma by
      fluorescence in situ hybridization (FISH) using probes for chromosome 3, 8q24,
      and 1p36. A total of 32 metastatic tumors were analyzed by FISH. Monosomy 3 was
      detected in 9 out of 16 (56.3%) cases of metastatic uveal melanoma but was not
      found in any of the 16 metastatic cutaneous melanomas (P < .001). With regard to
      1p36, amplifications were found in 8 out of 16 (50%) cases of metastatic
      cutaneous melanoma but not in any case of uveal melanoma (P < .05). 1p36 was
      deleted in 3 cases of uveal and 1 case of cutaneous melanoma. Amplifications of
      8q were found in 15 out of 16 (94%) cases of uveal melanoma metastases and in 12
      out of 16 (75%) cases of cutaneous metastases. The findings suggest that FISH for
      monosomy 3 is a useful adjunct tool in the differential diagnosis of metastatic
      uveal versus cutaneous melanoma.

PMID- 22415058
TI  - Polypoid intestinal metaplasia of the external urethral meatus.
AB  - A 33-year-old male patient presented with a 1.5-cm polypoid lesion at the edge of
      the urethral meatus that showed a gross appearance similar to that of a urethral
      caruncle in the female. The histological features revealed a superficially
      ulcerated lesion composed of colonic-type mucosal glands with focal regenerative
      atypia. This case appears to be the first reported one on an intestinal-type
      polyp in this site. The patient had no further problems after excisional biopsy.

PMID- 22415059
TI  - Nephrogenic adenoma of the urinary tract: a review.
AB  - Nephrogenic adenoma (NA) is an uncommon and intriguing lesion in the urinary
      tract. The pathogenesis of NA is not entirely clear. NA was considered to be a
      metaplastic process of the urothelium in response to chronic irritation of the
      urinary tract. However, recent evidence has shown that NA is not a metaplastic
      lesion but rather a proliferation of exfoliated and implanted renal epithelial
      cells in the urinary tract. Histologically, NAs exhibit, singly or in
      combination, tubules, small papillae, and microcystic structures lined by cells
      with little cytological atypia and focal hobnail changes. Solid formations and
      compressed spindled cells within a fibromyxoid background are rarely observed.
      Differential diagnosis includes, but is not limited to, malignant neoplasms
      occurring at the same sites, in particular urothelial carcinoma with deceptively
      bland morphology (with small tubules, microcystic and nested variants), prostatic
      adenocarcinoma, and clear cell adenocarcinoma. Immunohistochemical studies with
      antibodies targeting members of the paired box gene family (PAX2 and/or PAX8) in
      NAs may be helpful in the differential diagnosis of urothelial lesions and
      prostatic adenocarcinoma. NAs are most likely to be confused with clear cell
      adenocarcinoma, especially in small biopsy specimens. This is confounded by both
      lesions being frequently positive for PAX2, PAX8, and CK7 and not infrequently
      positive for p504S (alpha-methylacyl-CoA-racemase, AMACR) by
      immunohistochemistry. Recognition of its characteristic morphological patterns
      and awareness of its unusual architectural and cytological features are important
      in making the diagnosis of NA and distinguishing this lesion from its mimickers.

PMID- 22415060
TI  - UbcH10 expression in benign, hyperplastic, and malignant endometrial curetted
      materials: a tissue microarray study.
AB  - The aim of this study was to investigate the role of UbcH10 expression in the
      differential diagnosis of benign, hyperplastic, and malignant endometrial tissues
      and also the relationship of UbcH10 with the clinicopathologic parameters of
      malignant cases. A tissue microarray was performed for 81 endometrial curettage
      biopsies, which histological diagnosis had demonstrated to be 13 cases of
      proliferative endometrium, 7 cases of disordered proliferative endometrium, 5
      cases of complex atypical hyperplasia, 24 cases of nonatypical hyperplasia, and
      32 cases of endometrioid adenocarcinoma. Expression of UbcH10 was assessed by
      immunohistochemistry. When groups were compared according to UbcH10 percentages
      and scores, a statistically significant difference was found only between the
      carcinoma group and the other groups, except the complex atypical hyperplasia
      group (P < .05). In the malignant group, UbcH10 percentages and scores were only
      significantly related to age. There was no significant association between UbcH10
      expression and tumor grade and stage. Overexpression of UbcH10 may be a useful
      indicator of endometrial carcinoma. UbcH10 also deserves further evaluation in
      the detection of prognostic mean and also for its role in endometrial
      carcinogenesis.

PMID- 22415061
TI  - Accuracy of preoperative biopsies compared with surgical specimens in the
      diagnosis of colorectal adenocarcinoma.
AB  - OBJECTIVE: Since the first data from a patient with colorectal adenocarcinoma are
      obtained by biopsy, this study evaluated the accuracy of diagnosis by biopsy as
      compared with the diagnostic potential of the surgical specimen, considering the
      histological type, grade of differentiation, and immunohistochemical expression
      of p53. METHODS: The specimens were obtained from 80 patients assisted at
      Hospital Sao Paulo. The biopsy and surgical specimen sections were stained by
      hematoxylin-eosin and immunohistochemistry and compared by 3 pathologists blinded
      to the evaluations. RESULTS: The accuracy for the histological types was 88%. The
      grade of differentiation presented an accuracy of 70% with Kappa = .48. The
      expression of protein p53 exhibited an accuracy of 68% with Kappa = .22.
      CONCLUSION: The preoperative biopsy of colorectal adenocarcinoma presented good
      accuracy compared with histopathological examination of the surgical specimen,
      but with weak to moderate effective degree of agreement between the results.

PMID- 22415062
TI  - Plasmin system of Alzheimer's disease patients: CSF analysis.
AB  - Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder
      characterized by the extracellular deposit of Amyloid beta (Abeta), mainly of the
      Amyloid beta(1-42) (Abeta(1-42)) peptide in the hippocampus and neocortex leading
      to progressive cognitive decline and dementia. The possible imbalance between the
      Abeta production/degradation process was suggested to contribute to the
      pathogenesis of AD. Among others, the serine protease plasmin has shown to be
      involved in Abeta(1-42) clearance, a hypothesis strengthened by neuropathological
      studies on AD brains. To explore whether there is a change in plasmin system in
      CSF of AD patients, we analyzed CSF samples from AD and age-matched controls,
      looking at plasminogen, tissue plasminogen activator (t-PA) and plasminogen
      activator inhibitor (PAI-1) protein levels and t-PA and urokinase plasminogen
      activator (u-PA) enzymatic activities. We also measured Abeta(1-42), total-tau
      and phospho-tau (181) CSF levels and sought for a possible relationship between
      them and plasmin system values. Our findings showed that t-PA, plasminogen and
      PAI-1 levels, as t-PA enzymatic activity, remained unchanged in AD with respect
      to controls; u-PA activity was not detected. We conclude that CSF analysis of
      plasminogen system does not reflect changes observed post-mortem. Unfortunately,
      the CSF detection of plasmin system could not be a useful biomarker for either AD
      diagnosis or disease progression. However, these findings do not exclude the
      possible involvement of the plasmin system in AD.

PMID- 22415063
TI  - Multidimensional plasma protein separation technique for identification of
      potential Alzheimer's disease plasma biomarkers: a pilot study.
AB  - Neurochemical differential diagnosis between Alzheimer's disease and other
      dementias is currently based on CSF biomarkers. Here, we report a method by which
      potential biomarkers can be identified in blood. Blood plasma samples from seven
      well-characterized Alzheimer's patients and seven non-Alzheimer's patients were
      subjected to a multi-dimensional protein separation procedure. After removal of
      12 high-abundance proteins, the depleted samples from both diagnostic groups were
      labeled with different fluorescent dyes, mixed and separated by anion exchange
      and RP-chromatography. The resulting chromatography fractions were analyzed on 2D
      gels. Twenty significant differentially expressed proteins were identified by
      mass spectrometry analysis. Ten of these proteins were either involved in the
      pathophysiology of Alzheimer's disease or the amyloid/Abeta-peptide processing
      pathway. This work demonstrated a successful application of a multidimensional
      separation technique and holds the potential to identifying blood-based
      biomarkers for other diseases in the future.

PMID- 22415065
TI  - Changes in breathing pattern and thoracoabdominal motion after bariatric surgery:
      a longitudinal study.
AB  - This study evaluated the breathing pattern of 30 obese patients [32 +/- 9 years
      old; body mass index (BMI): 42.72 +/- 4.10 kg/m(2)] before and after bariatric
      surgery and compared them with 30 control individuals (31 +/- 8 years old, BMI:
      21.99 +/- 2.22 kg/m(2)). Measurements were performed using calibrated respiratory
      inductive plethysmography. Six months after bariatric surgery, obese patients
      exhibited a significant reduction in tidal volume (V(T)), minute ventilation
      (V(E)) and inspiratory duty cycle (T(I)/T(TOT)) compared with pre-surgical
      values. The control group had a higher breathing frequency, V(E) and phase angle
      (PhAng). There were no significant differences in V(T)/T(I), percentage of rib
      cage motion (%RC) or abdominal motion (%AB). Obese patients exhibited changes in
      their breathing pattern and asynchrony after bariatric surgery without any
      changes in thoracoabdominal motion. Certain aspects of the breathing pattern of
      obese patients became more similar to those of the controls after surgery.

PMID- 22415064
TI  - Role of autophagy inhibitors and inducers in modulating the toxicity of
      trimethyltin in neuronal cell cultures.
AB  - Trimethyltin (TMT) is a triorganotin compound which determines neurodegeneration
      of specific brain areas particularly damaging the limbic system. Earlier
      ultrastructural studies indicated the formation of autophagic vacuoles in neurons
      after TMT intoxication. However, no evaluation has been attempted to determine
      the role of the autophagic pathway in TMT neurotoxicity. To assess the
      contribution of autophagy to TMT-induced neuronal cell death, we checked the
      vulnerability of neuronal cultures to TMT after activation or inhibition of
      autophagy. Our results show that autophagy inhibitors (3-methyladenine and L
      asparagine) greatly enhanced TMT neurotoxicity. Conversely, known activators of
      autophagy, such as lithium and rapamycin, displayed neuroprotection against this
      toxic compound. Due to its diverse targets, the action of lithium was complex.
      When lithium was administered according to a chronic treatment protocol (6 days
      pretreatment) it was able to rescue both hippocampal and cortical neurons from
      TMT (or from glutamate toxicity used as reference). This effect was accompanied
      by an increased phosphorylation of glycogen synthase kinase 3 which is a known
      target for lithium neuroprotection. If the pre-incubation time was reduced to 2 h
      (acute treatment protocol), lithium was still able to counteract TMT toxicity in
      hippocampal but not in cortical neurons. The neuroprotective effect of lithium
      acutely administered against TMT in hippocampal neurons can be completely
      reverted by an excess of inositol and is possibly related to the inactivation of
      inositol monophosphatase, a key regulator of autophagy. These data indicate that
      TMT neurotoxicity can be dramatically modified, at least in vitro, by lithium
      addition which seems to act through different mechanisms if acutely or
      chronically administered.

PMID- 22415066
TI  - Effect of airway inflammation on short-latency reflex inhibition to inspiratory
      loading in human scalene muscles.
AB  - The short-latency reflex inhibition of human inspiratory muscles produced by
      loading is prolonged in asthma and obstructive sleep apnoea, both diseases
      involving airway and systemic inflammation. Both diseases also involve repetitive
      inspiratory loading. Although airway mucosal afferents are not critical
      components of the normal reflex arc, during airway inflammation, prolongation of
      the reflex may be caused by altered mucosal afferent sensitivity, or altered
      central processing of their inputs. We hypothesised that acute viral airway
      inflammation would replicate the reflex abnormality. The reflex was tested in 9
      subjects with a "common cold" during both the acute infection and when well.
      Surface electrodes recorded electromyographic (EMG) activity bilaterally from
      scalene muscles. Latencies of the inhibitory response (IR) did not differ
      significantly (IR peak 67 vs 70 ms (p=0.12), and IR offset 87 vs 90 ms (p=0.23),
      between the inflamed and well conditions, respectively). There was no difference
      in any measure of the size of the reflex inhibition.

PMID- 22415068
TI  - Human herpes virus 6-associated myelitis following allogeneic bone marrow
      transplantation.

PMID- 22415067
TI  - Thrombosis and severe asthenia as priority manifestations in paroxysmal nocturnal
      haemoglobinuria.

PMID- 22415069
TI  - Briefs on insulin and innate immune response.
AB  - Insulin is a pivotal regulator of glucose metabolism and exerts an important
      anabolic function throughout the body. Insulin commands the glucose uptake by the
      cells and might control the processes in which there is need for energy such as
      mitogenesis and gene transcription. In certain conditions, diabetes mellitus for
      example, when insulin is diminished, the homeostasis of many tissues and organs
      are broken what can lead to a higher mortality due to an enhanced susceptibility
      to infections. This vulnerability to infections can partially be explained by a
      change in response to inflammation. In fact, diabetic animals and patients show a
      deficient inflammatory response. Many animal models have shown that neutrophils
      chemotaxis and recruitment are dampened and macrophages from diabetic patients
      have low phagocytic and microbicidal activities. In most cases, once insulin
      therapy is introduced, clinical symptoms and signs can be reverted. In addition,
      there are a number of studies trying to demystify pathways under insulin command.
      Researchers are also trying to understand how insulin is able to keep
      inflammatory response under control, restores innate immune cells ability to
      fight against pathogens and harmlessly activates adaptive immunity response. This
      review provides an overview on how inflammatory response is driven in the absence
      of insulin in diabetes and discusses recent findings on the influence of insulin
      on innate imune response. At the end, some signaling pathways are also
      highlighted and important enzymes and proteins that control DNA transcription are
      presented.

PMID- 22415070
TI  - The suppressive effects of Bursopentine (BP5) on oxidative stress and NF-KB
      activation in lipopolysaccharide-activated murine peritoneal macrophages.
AB  - BACKGROUND/AIM: Bursopentine (BP5) is a novel thiol-containing pentapeptide
      isolated from chicken bursa of Fabricius, and is reported to exert
      immunomodulatory effects on B and T lymphocytes. It has been found that some
      thiol compounds, such as glutathione (GSH) and N-acetylcysteine (NAC) protect
      living cells from oxidative stress. This led us to investigate whether BP5 had
      any ability to protect macrophages from oxidative stress as well as any mechanism
      that might underlie this process. METHODS: Murine peritoneal macrophages
      activated by lipopolysaccharide (LPS) (2 MUg/ml) were treated with single bouts
      (0, 25, 50, and 100 MUM) of BP5. RESULTS: BP5 potently suppressed the markers for
      oxidative stress, including nitric oxide (NO), reactive oxygen species (ROS),
      lipid peroxidation, and protein oxidation. It also decreased the expression and
      activity of inducible nitric oxide synthase (iNOS) and promoted a protective
      antioxidant state by elevating GSH content and by activating the expression and
      activity of certain key antioxidant and redox enzymes, including glutathione
      peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and
      catalase (CAT). This suppressive effect on oxidative stress was accompanied by
      down-regulated expression and activity of nuclear factor kappa B (NF-kappaB).
      CONCLUSION: These findings demonstrate that BP5 can protect LPS-activated murine
      peritoneal macrophages from oxidative stress. BP5 may have applications as an
      anti-oxidative stress reagent.

PMID- 22415071
TI  - Effect of thymoquinone on cytosolic pH and Na+/H+ exchanger activity in mouse
      dendritic cells.
AB  - The anti-inflammatory Nigella sativa component thymoquinone compromises the
      function of dendritic cells (DCs), key players in the regulation of innate and
      adaptive immunity. DC function is regulated by the Na(+)/H(+) exchanger (NHE),
      which is stimulated by lipopolysaccharides (LPS) and required for LPS-induced
      cell swelling, reactive oxygen species (ROS) production, TNF-alpha release and
      migration. Here we explored, whether thymoquinone influences NHE activity in DCs.
      To this end, bone marrow derived mouse DCs were treated with LPS in the absence
      and presence of thymoquinone (10 MUM). Cytosolic pH (pH(i)) was determined from
      2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence, NHE
      activity from the Na(+)-dependent realkalinization following an ammonium pulse,
      cell volume from forward scatter in FACS analysis, ROS production from 2',7'
      dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, TNF-alpha production
      utilizing ELISA and DC migration with transwell migration assays. As a result,
      exposure of DCs to LPS (1 MUg/ml) led within 4 hours to transient increase of NHE
      activity. Thymoquinone did not significantly modify cytosolic pH or cellular NHE
      activity in the absence of LPS, but abrogated the effect of LPS on NHE activity.
      Accordingly, in the presence of thymoquinone LPS-treatment resulted in cytosolic
      acidification. LPS further increased forward scatter and ROS formation, effects
      similarly abrogated by thymoquinone. Again, in the absence of LPS, thymoquinone
      did not significantly modify ROS formation and cell volume. LPS further triggered
      TNF-alpha release and migration, effects again blunted in the presence of
      thymoquinone. NHE1 inhibitor cariporide (10 MUM) blunted LPS induced TNF-alpha
      release and migration. The effects of thymoquinone on NHE activity and migration
      were reversed upon treatment of the cells with t-butyl hydroperoxide (TBOOH, 5
      MUM). In conclusion, thymoquinone blunts LPS induced NHE activity, cell swelling,
      oxidative burst, cytokine release and migration of bone marrow derived murine
      dendritic cells. NHE inhibition may thus contribute to the antiinflammatory
      action of thymoquinone.

PMID- 22415072
TI  - TP-58, a novel thienopyridine derivative, protects mice from concanavalinA
      induced hepatitis by suppressing inflammation.
AB  - Hepatitis represents a ubiquitous human health problem but effective therapies
      with limited side effects are still lacking. In this study, we investigated the
      effect and mechanism of TP-58, a novel thienopyridine derivative, on a murine
      fulminant hepatitis model induced by concanavalin A (ConA). We found TP-58
      markedly alleviated ConA-caused liver injury and increased survival ratio of mice
      injected with a lethal dose of ConA. Oral administration of TP-58 significantly
      alleviated ConA-caused liver injury in mice by the reduction of serum
      aminotransferases and liver necrosis.The analysis of proinflammatory cytokines
      showed that TP-58 decreased both hepatic mRNA expressions and serum protein
      levels of TNF-alpha and IL-6. And the result from LPS-stimulated RAW 264.7 cells
      showed TP-58 suppressed the production of TNF-alpha, IL-6, and Nitro Oxide (NO)
      in the supernatant of LPS-stimulated RAW 264.7 cells. The study of activation of
      nuclear factor-kappaB (NF-kappaB) by electrophoretic mobility shift assay (EMSA)
      showed that TP-58 inhibited the activation of NF-kappaB both in vivo and in
      vitro. The inhibitory effect was also accompanied by a parallel reduction of
      IkappaB phosphorylation. These results indicate that TP-58 protects against liver
      injury by inhibition of the NF-kappaB-mediated inflammation and suggest a
      potential role of TP-58 against acute liver injury and other inflammatory
      diseases.

PMID- 22415073
TI  - Reduced hepatic injury in Toll-like receptor 4-deficient mice following D
      galactosamine/lipopolysaccharide-induced fulminant hepatic failure.
AB  - Liver transplantation is the only therapy of proven benefit in fulminant hepatic
      failure (FHF). Lipopolysaccharide (LPS), D-galactosamine (GalN)-induced FHF is a
      well established model of liver injury in mice. Toll-Like Receptor 4 (TLR4) has
      been identified as a receptor for LPS. The aim of this study was to investigate
      the role of TLR4 in FHF induced by D-GalN/LPS administration in mice. Wild type
      (WT) and TLR4 deficient (TLR4ko) mice were studied in vivo in a fulminant model
      induced by GalN/LPS. Hepatic TLR4 expression, serum liver enzymes, hepatic and
      serum TNF-alpha and interleukin-1beta levels were determined. Apoptotic cells
      were identified by immunohistochemistry for caspase-3. Nuclear factor-kappabeta
      (NF-kappa beta) and phosphorylated c-Jun hepatic expression were studied using
      Western blot analysis. All WT mice died within 24 hours after administration of
      GalN/LPS while all TLR4ko mice survived. Serum liver enzymes, interleukin-1beta,
      TNF-alpha level, TLR4 mRNA expression, hepatic injury and hepatocyte apoptosis
      all significantly decreased in TLR4ko mice compared with WT mice. A significant
      decrease in hepatic c-Jun and IkappaB signaling pathway was noted in TLR4ko mice
      compared with WT mice. In conclusion, following induction of FHF, the
      inflammatory response and the liver injury in TLR4ko mice was significantly
      attenuated through decreased hepatic c-Jun and NF-kappaB expression and thus
      decreased TNF-alpha level. Down-regulation of TLR4 expression plays a pivotal
      role in GalN/LPS induced FHF. These findings might have important implications
      for the use of the anti TLR4 protein signaling as a potential target for
      therapeutic intervention in FHF.

PMID- 22415074
TI  - Anti-fibrotic effects via regulation of transcription factor Sp1 on hepatic
      stellate cells.
AB  - BACKGROUND: Hepatic stellate cells (HSCs), the central cells in hepatic fibrosis,
      are characterized by sustaining activation, a process that consists in increased
      proliferation and over-expression of fibrotic genes. Transcription factor Sp1
      mediates the expression of a variety of fibrotic genes expression and thereby
      play an important role in fibrosis. In addition, previous reports have indicated
      that Sp1 binding activity is greatly increased in activated HSCs. Thus, our aim
      was to investigate the anti-proliferative and anti-fibrotic effects of the
      oligonuceotide decoy of the transcription factor Sp1, ODN, a potent inhibitor of
      Sp1-activated transcription. METHODS: We optimized Lipofectamin 2000 (LF2000):ODN
      DNA ratio for the transfection of hepatic stellate cells HSC-T6. Then we measure
      the effect of transfected ODN on HSC-T6 cells' proliferation and fibrotic gene
      expression, and study the mechanism involved. RESULTS: At a DNA concentration of
      1 MUM and a ratio ODN DNA:LF2000 of 1:3, HSC-T6 cells have the maximal
      transfection efficiency with the lowest toxicity. Transfected ODN effectively
      blocks Sp1 binding to the promoter regions of cell cycle regulatory proteins
      cyclin D1, p27(KIP1) and fibrotic genes, including transforming growth factor
      (TGF)-beta1, Platelet-derived growth factor (PDGF)-BB, alpha-SMA, alpha1 (I)
      collagen and tissue inhibitor of metalloproteinases-1 (TIMP-1). ODN inhibits HSC
      T6 proliferation and fibrotic genes expression in vitro. CONCLUSION: Sp1 is a key
      transcription factor that mediates proliferation and fibrotic gene synthesis of
      HSC-T6, inhibition of Sp1 with decoy ODN may be an effective approach to prevent
      the progression of hepatic fibrosis.

PMID- 22415075
TI  - Expression of TMEM16A and SLC4A4 in human pancreatic islets.
AB  - BACKGROUND/AIMS: Stimulation of insulin release by D-glucose is accompanied by
      Cl(-) and HCO(3)(-) efflux from pancreatic islet cells. The efflux of these
      anions may involve volume-regulated anion channels, including possibly TMEM16A,
      and the Na(+)-HCO(3)(-)-cotransporter SLC4A4. The present study was designed to
      explore the expression of both TMEM16A and SLC4A4 in human pancreatic islets.
      METHODS: Pancreases were obtained from human cadaveric donors. Immunodetection of
      TMEM16A and SLC4A4 was performed by immunohistochemistry on sections of fixed
      pancreas, while real-time PCR for the study of corresponding gene expression was
      performed on RNA extracted from both total pancreatic pieces and isolated
      pancreatic islets. RESULTS: RT-PCR yielded lower levels of SLC4A4 in isolated
      islets than in the total pancreas, whilst a mirror image prevailed for TMEM16A
      mRNA. Immunohistochemistry of human pancreas, however, indicated comparable
      immunostaining of SLC4A4 in insulin-producing cells and exocrine pancreatic
      cells, whilst that of TMEM16A appeared less pronounced in insulin-producing cells
      than in exocrine cells. CONCLUSION: The present findings support the view that,
      in humans like in rodent, the regulation of anion fluxes in insulin-producing
      cells may involve both SLC4A4 and TMEM16A.

PMID- 22415076
TI  - A new role for aquaporin 7 in insulin secretion.
AB  - BACGROUNS/AIMS: Several insulinotropic agents were recently reported to cause
      beta-cell swelling. The possible participation of AQP7 to water transport was
      investigated in AQP7(+/+) or AQP7(-/-) mice. METHODS: Aquaporin expression,
      insulin secretion, cell swelling and electrical activity were investigated in
      pancreatic islets. RESULTS: RT-PCR revealed the expression of AQP5 and AQP8 mRNA.
      Double immunofluorescent labeling indicated their presence in beta-cells. Whilst
      basal insulin release from isolated pancreatic islets incubated at 2.8 mM D
      glucose did not differ between AQP7(+/+) or AQP7(-/-) mice, the secretion of
      insulin evoked by the omission of 50 mM NaCl, the substitution of 50 mM NaCl by
      100 mM glycerol or a rise in D-glucose concentration to 8.3 mM and 16.7 mM was
      severely impaired in the islets from AQP7(-/-) mice. Yet, exposure of beta-cells
      to either the hypotonic medium or a rise in D-glucose concentration caused a
      similar degree of swelling and comparable pattern of electrical activity in cells
      from AQP7(+/+) and AQP7(-/-) mice. Both the cell swelling and change in membrane
      potential were only impaired in AQP7(-/-) cells when exposed to 50 mM glycerol.
      CONCLUSION: It is proposed, therefore, that AQP7 may, directly or indirectly,
      play a role at a distal site in the exocytotic pathway.

PMID- 22415077
TI  - Effect of the AMP-kinase modulators AICAR, metformin and compound C on insulin
      secretion of INS-1E rat insulinoma cells under standard cell culture conditions.
AB  - BACKGROUND/AIMS: The function of beta-cells is regulated by nutrient uptake and
      metabolism. The cells' metabolic state can be expressed as concentration ratios
      of AMP, ADP and ATP. Relative changes in these ratios regulate insulin release.
      An increase in the intracellular ATP concentration causes closure of K(ATP)
      channels and cell membrane depolarization, which triggers stimulus-secretion
      coupling (SSC). In addition to K(ATP) channels, the AMP-dependent protein kinase
      (AMPK), a major cellular fuel sensor in a variety of cells and tissues, also
      affects insulin secretion and beta-cell survival. In a previous study we found
      that the widely used AMPK inhibitor compound C retards proliferation and induces
      apoptosis in the rat beta-cell line INS-1E. We therefore tested the effects of
      AMPK activators (AICAR and metformin), and compound C on AMPK phosphorylation,
      insulin secretion, K(ATP) channel currents, cell membrane potential,
      intracellular calcium concentration, apoptosis and cell cycle distribution of INS
      1E cells under standard cell culture conditions (11 mM glucose). METHODS: Western
      blotting, ELISA, patch-clamp, calcium imaging and flow cytometry. RESULTS: We
      found that basal AMPK phosphorylation is enhanced by AICAR (1 mM) and metformin
      (1 mM) but remained unaffected by compound C (10 MUM). Both AICAR and compound C
      stimulated basal insulin secretion whereas metformin had no effect. Pre
      incubation with AICAR (1 mM) caused an inhibition of K(ATP) currents but did not
      significantly alter the average cell membrane potential (Vm) or the threshold
      potential of electrical activity. Acute administration of AICAR (300 MUM) led to
      a depolarization of Vm, which was not due to an inhibition of the basal- or
      glucose-induced chloride conductance, and was not accompanied by elevations of
      intracellular calcium (Ca(i)). AICAR had no additive blocking effect on K(ATP)
      currents when applied together with tolbutamide. Compound C applied over 24 hours
      induced an increase in the percentage of cells positive for caspase activity,
      whereas AICAR (1 mM) applied for 48 hours was without effect. Medium glucose
      concentration <3 mM caused cell cycle arrest, caspase activation and an increase
      of cell granularity. CONCLUSION: We conclude that under standard cell culture
      conditions the AMPK modulators AICAR and compound C, but not metformin, stimulate
      insulin secretion by AMPK-independent mechanisms.

PMID- 22415078
TI  - Effects of zinc and DHA on the epigenetic regulation of human neuronal cells.
AB  - Dietary intake of zinc and omega-3 fatty acids (DHA) have health benefits for a
      number of human diseases. However, the molecular basis of these health benefits
      remains unclear. Recently, we reported that zinc and DHA affect expression levels
      of histones H3 and H4 in human neuronal M17 cells. Here, using immunoblotting and
      densitometric analysis, we aimed to investigate the effect of zinc and DHA on
      post-translational modifications of histone H3 in M17 cells. In response to
      increase in zinc concentration, we observed increase in deacetylation,
      methylation and phosphorylation of H3 and decrease in acetylation. We also
      investigated the role of zinc in apoptosis, and found that zinc reduced the
      levels of the anti-apoptotic marker Bcl-2 while increasing the apoptotic marker
      caspase-3 levels, correlating with cell viability assays. Conversely, DHA
      treatment resulted in increase in acetylation of H3 and Bcl-2 levels and decrease
      in deacetylation, methylation, phosphorylation of H3 and caspase-3 levels,
      suggesting that DHA promotes gene expression and neuroprotection. Our novel
      findings show the opposing effects of zinc and DHA on the epigenetic regulation
      of human neuronal cells and highlight the potential benefit of dietary intake of
      DHA for management of neurodegenerative diseases.

PMID- 22415079
TI  - Heme oxygenase (HO-1) rescue of adipocyte dysfunction in HO-2 deficient mice via
      recruitment of epoxyeicosatrienoic acids (EETs) and adiponectin.
AB  - BACKGROUND/AIMS: HO-1 and EETs are functionally linked and their interactions
      influence body weight, insulin sensitivity, and serum levels of inflammatory
      cytokines in metabolic syndrome phenotype of HO-2 null mice. The HO-2 isozyme is
      essential for regulating physiological levels of ROS. Recent studies have
      suggested a potential role of EET in modifying adipocyte differentiation through
      up-regulation of HO-1-adiponectin-AkT signaling in human mesenchymal stem cells
      (MSCs). Our aim was to examine the consequences of HO deficiency on MSC-derived
      adipogenesis in vitro using MSC derived from HO-2 null and WT mice in vivo.
      METHODS: Four-month-old HO-2 null (HO-2(-/-)) and B6/129SF2/J (WT) mice were
      divided into three groups (four mice/group): WT, HO-2(-/-), and HO-2(-/-) +CoPP.
      Adipogenesis was performed on purified MSC-derived adipocytes cultured in
      adipogenic differentiation media and an EET-agonist was added every 3 days.
      RESULTS: HO-2 depletion of MSC adipocytes resulted in increased adipogenesis
      (p<0.01) and increased levels of inflammatory cytokines including (TNF)-alpha
      (p<0.05), (MCP)-1 (p<0.05), and (IL-1)-beta (p<0.05). These results were
      accompanied by decreases in HO-1 (p<0.05) and subsequently EET and HO activity
      (p<0.05). Up-regulation of HO-1 resulted in decreased MSC-derived adipocyte
      differentiation, decreased production of TNF-alpha and MCP-1 and increased levels
      of adiponectin (p<0.05). Cyp2J5 (p<0.05), HO-1 (p<0.05), and adiponectin mRNA
      levels (p<0.05) were also decreased in visceral adipose tissue isolated from HO-2
      null compared to WT mice. EET agonist stimulation of MSC adipocytes derived from
      HO-2 null mice yielded similar results. CONCLUSION: Increased levels of EET and
      HO-1 are essential for protection against the adverse effects of adipocyte
      hypertrophy and the ensuing metabolic syndrome. These results offer a portal into
      therapeutic approaches for the prevention of the metabolic syndrome.

PMID- 22415080
TI  - Long-term neuropeptide Y administration in the periphery induces abnormal
      baroreflex sensitivity and obesity in rats.
AB  - Neuropeptide Y (NPY) is an important neuronal element involved in cardiovascular
      regulation. Since elevated plasma levels of NPY have been observed in numerous
      pathological situations, this study aimed to determine whether long-term elevated
      plasma concentrations of NPY could result in aberrant baroreflex sensitivity.
      Mini-osmotic pump containing NPY (85 MUg per 30 days) was subcutaneously
      implanted between scapulae in male rats for 4 months. The rats treated with NPY
      showed the following characters compared with control group: (1) attenuated heart
      rate responding to the increases in mean arterial blood pressure (MABP) induced
      by phenylephrine, but enhanced heart rate responding to the decreases in MABP
      induced by sodium nitroprusside; (2) decreased protein levels of substance P (SP)
      and GluR2, while increased the expression of gamma-aminobutyric acid A receptor
      (GABA(A)R) in brainstem; (3) abdominal obesity indicated by increased body weight
      and accumulated fat mass in peritoneal cavity; (4) significant increases in total
      cholesterol, triglycerides, and low density lipoprotein levels in the periphery.
      These findings indicate that long-term NPY administration in the periphery leads
      to abnormal baroreflex sensitivity due, at least in part, to the down-regulated
      expression of SP/GluR2 and elevated expression of GABA(A)R in both protein and
      RNA levels, which indicate the alternations in glutamate function and GABA action
      in the nucleus tractus solitarii in NPY-treated rats. Furthermore, long-term NPY
      administration results in abdominal obesity and dyslipidemia.

PMID- 22415081
TI  - Benzo[a]pyrene potentiates the pathogenesis of abdominal aortic aneurysms in
      apolipoprotein E knockout mice.
AB  - The objective of this study was to determine the effect of benzo[a]pyrene (BaP),
      an abundant environmental polycyclic aromatic hydrocarbon compound, on the
      pathogenesis of abdominal aortic aneurysms (AAA). Earlier studies have shown that
      BaP promotes vasculopathy, including atherosclerosis, a predisposing factor for
      AAA development. In two experimental arms, 203 apolipoprotein E knockout (ApoE-/
      ) mice were evaluated in 4 groups: BaP, angiotensin II (AngII), BaP+AngII and
      control. Mice in the first arm were exposed to 5mg/kg/week of BaP for 42 days,
      and in the second arm to 0.71mg/kg daily for 60 days. In arm one, AAA incidence
      was higher in the BaP+AngII (14/28) versus AngII (8/27) group (p < 0.05), rupture
      (n=3) was observed only in BaP+AngII treated mice (p < 0.05). In the second arm,
      AAA incidence did not differ between AngII (17/30) and BaP+AngII (16/29) groups.
      However, intact AAA diameter was larger in the BaP+AngII (2.3 +/- 0.1mm) versus
      AngII (1.9 +/- 0.1mm) group (p < 0.05), but AAA rupture did not differ (p=NS). In
      both experimental arms, BaP+AngII mice showed increased expression of tumor
      necrosis factor alpha (TNF-alpha), cyclophilin A (Cyp A), and matrix
      metalloproteinase-9 (MMP9) (p < 0.05). No AAA occurred in control or BaP groups.
      These findings suggest the role of BaP exposure in potentiating AAA pathogenesis,
      which may have potential public health significance.

PMID- 22415082
TI  - Mitochondrial molecular basis of sevoflurane and propofol cardioprotection in
      patients undergoing aortic valve replacement with cardiopulmonary bypass.
AB  - BACKGROUND/AIMS: Study elucidates and compares the mitochondrial bioenergetic
      related molecular basis of sevoflurane and propofol cardioprotection during
      aortic valve replacement surgery due to aortic valve stenosis. METHODS: Twenty
      two patients were prospectively randomized in two groups regarding the anesthetic
      regime: sevoflurane and propofol. Hemodynamic parameters, biomarkers of cardiac
      injury and brain natriuretic peptide (BNP) were measured preoperatively and
      postoperatively. In tissue samples, taken from the interventricular septum, key
      mitochondrial molecules were determined by Western blot, real time PCR, as well
      as confocal microscopy and immunohisto- and immunocyto-chemical analysis.
      RESULTS: The protein levels of cytochrome c oxidase and ATP synthase were higher
      in sevoflurane than in propofol group. Nevertheless, cytochrome c protein content
      was higher in propofol than sevoflurane receiving patients. Propofol group also
      showed higher protein level of connexin 43 (Cx43) than sevoflurane group.
      Besides, immunogold analysis showed its mitochondrial localization. The mRNA
      level of mtDNA and uncoupling protein (UCP2) were higher in propofol than
      sevoflurane patients, as well. On the other hand, there were no significant
      differences between groups in hemodynamic assessment, intensive care unit length
      of stay, troponin I and BNP level. CONCLUSIONS: Our data indicate that
      sevoflurane and propofol lead to cardiac protection via different mitochondrially
      related molecular mechanisms. It appears that sevoflurane acts regulating
      cytochrome c oxidase and ATP synthase, while the effects of propofol occur
      through regulation of cytochrome c, Cx43, mtDNA transcription and UCP2.

PMID- 22415083
TI  - Granulocyte colony stimulating factor prevents kidney infarction and attenuates
      renovascular hypertension.
AB  - BACKGROUND: G-CSF is a critical regulator of hematopoietic cell proliferation,
      differentiation and survival. It has been reported that G-CSF attenuates renal
      injury during acute ischemia-reperfusion. In this study we evaluated the effects
      of G-CSF on the renal and cardiovascular systems of 2K1C hypertensive mice.
      METHODS: Male C57BL/6 mice were subjected to left renal artery clipping (2K1C) or
      sham operation and were then administered G-CSF (100 MUg/kg/day) or vehicle for
      14 days. RESULTS: Arterial pressure was higher in 2K1C + vehicle animals than in
      2K1C + G-CSF (150+/-5 vs. 129+/-2 mmHg, p<0.01, n=8). Plasma angiotensin I, II
      and 1-7 concentrations were significantly increased in 2K1C + Vehicle when
      compared to the normotensive Sham group. G-CSF prevented the increase of these
      vasoactive peptides. The clipped kidney/contralateral kidney weight ratio showed
      a less atrophy of the ischemic kidney in the treated group (0.50+/-0.02 vs.
      0.66+/-0.01, p<0.05). The infarction area in the clipped kidney was completely
      prevented in 7 out of 8 2K1C + G-CSF mice. Administration of G-CSF protected the
      clipped kidney from apoptosis. CONCLUSION: Our data indicate that G-CSF prevents
      kidney infarction and markedly attenuates the increases in plasma angiotensin
      levels and hypertension in 2K1C mice, reinforcing the protective effect of G-CSF
      on kidney ischemia.

PMID- 22415084
TI  - Expression of junctional adhesion molecule-C on the surface of platelets supports
      adhesion, but not differentiation, of human CD34 cells in vitro.
AB  - BACKGROUND: CD34(+) progenitor cells play an important role in haematopoiesis and
      vascular homeostasis. The aim of the present study was to investigate the role of
      platelet-derived junctional adhesion molecule-C (JAM-C) in adhesion and
      differentiation of human CD34(+) cells in vitro, as well as its association with
      platelet-derived P-selectin in patients with coronary artery disease. METHODS AND
      RESULTS: Using flow cytometry we observed that JAM-C expression on the surface of
      washed platelets is increased after activation with thrombin receptor activating
      peptide-6 in vitro and correlated with platelet-derived P-selectin expression in
      patients with coronary artery disease (r=0.326, P=0.007). The role of JAM-C and
      its counter receptor Mac-1 in adhesion of human CD34(+) cells over immobilized
      platelets was investigated by using a neutralizing soluble protein (sJAM-C-Fc)
      and a monoclonal antibody against JAM-C or integrin Mac-1 (CD11b/CD18). Treatment
      with soluble JAM-C-Fc or anti-JAM-C or anti-Mac-1, but not with control-Fc or
      IgG1, resulted in a significantly decreased adhesion of human CD34(+) cells to
      platelets under static conditions (P<0.05). In order to validate our findings
      under high shear stress we performed flow chamber experiments. In a similar
      manner, inhibiting JAM-C interaction with Mac-1 resulted in a significantly
      decreased adhesion of CD34(+) cells over immobilized platelets under high shear
      stress (P<0.05). Colony forming unit assays and coculture assays revealed that
      inhibition of JAM-C/Mac-1 axis did not influence the platelet-mediated
      differentiation of CD34(+) cells to endothelial cells or to macrophages/foam
      cells. CONCLUSIONS: Taken together a platelet-derived JAM-C supports CD34(+) cell
      adhesion, a mechanism potentially involved in homing as well as domiciliation of
      human CD34(+) cells.

PMID- 22415085
TI  - Interaction of diesel exhaust particles with human, rat and mouse erythrocytes in
      vitro.
AB  - Inhaled ultrafine (nano) particles can translocate into the bloodstream and
      interact with circulatory cells causing systemic and cardiovascular events. To
      gain more insight into this potential mechanism, we studied the interaction of
      diesel exhaust particles (DEP) with human, rat and mouse erythrocytes in vitro.
      Incubation of erythrocytes with DEP (1, 10 or 100 MUg/ml) for 30 min caused the
      highest hemolytic effect (up to 38%) in rats, compared to small but significant
      hemolysis in mice (up to 2.5%) and humans (up to 0.7%). Transmission electron
      microscopy of erythrocytes revealed the presence of variable degrees of ultrafine
      (nano)-sized aggregates of DEP either internalized and/or adsorbed onto the
      erythrocytes in the three species. A significant amount of DEP was found in rat
      and mouse (but not human) erythrocytes. Lipid erythrocyte susceptibility to in
      vitro peroxidation measured by malondialdehyde showed a significant and dose
      dependent increase in erythrocytes of rats, but not humans or mice. Unlike in
      human erythrocytes, total antioxidant status (TAS) and superoxide dismutase (SOD)
      activity in rats were significantly and dose- dependently decreased. In mouse
      erythrocytes, DEP caused a decreased in SOD (at 10 MUg/ml) and TAS (at 100
      MUg/ml) activities. In conclusion, DEP caused species-dependent erythrocyte
      hemolysis and oxidative stress, and were either taken up and/or adsorbed onto the
      red blood cells. Rat (and to a lesser degree mouse) erythrocytes were susceptible
      to DEP. Human erythrocytes showed the highest resistance to the observed effects.
      These species difference should be noted when using rats and mice blood as models
      for humans.

PMID- 22415086
TI  - Protein kinase CK1alpha regulates erythrocyte survival.
AB  - Protein kinase CK1 (casein kinase 1) isoforms are involved in the regulation of
      various physiological functions including apoptosis. The specific CK1 inhibitor
      D4476 may either inhibit or foster apoptosis. Similar to apoptosis of nucleated
      cells, eryptosis, the suicidal death of erythrocytes, is paralleled by cell
      shrinkage and cell membrane scrambling with phosphatidylserine exposure at the
      cell surface. Triggers of eryptosis include increase of cytosolic Ca(2+) activity
      following energy depletion (removal of glucose) or oxidative stress (exposure to
      the oxidant tert-butyl hydroperoxide [TBOOH]). Western blotting was utilized to
      verify that erythrocytes express the protein kinase CK1alpha, and FACS analysis
      to determine whether the CK1 inhibitor D4476 and CK1alpha activator pyrvinium
      pamoate modify forward scatter (reflecting cell volume), annexin V binding
      (reflecting phosphatidylserine exposure), and Fluo3 fluorescence (reflecting
      cytosolic Ca(2+) activity). As a result, both, human and murine erythrocytes
      express CK1 isoform alpha. Glucose depletion (48 hours) and exposure to 0.3 mM
      TBOOH (30 minutes) both decreased forward scatter, increased annexin V binding
      and increased Fluo3 fluorescence. CK1 inhibitor D4476 (10 MUM) significantly
      blunted the decrease in forward scatter, the increase in annexin V binding and
      the increase in Fluo 3 fluorescence. (R)-DRF053, another CK1 inhibitor, similarly
      blunted the increase in annexin V binding upon glucose depletion. The CK1alpha
      specific activator pyrvinium pamoate (10 MUM) significantly enhanced the increase
      in annexin V binding and Fluo3 fluorescence upon glucose depletion and TBOOH
      exposure. In the presence of glucose, pyrvinium pamoate slightly but
      significantly increased Fluo3 fluorescence. In conclusion, CK1 isoform alpha
      participates in the regulation of erythrocyte programmed cell death by modulating
      cytosolic Ca(2+) activity.

PMID- 22415087
TI  - Zinc at cytotoxic concentrations affects posttranscriptional events of gene
      expression in cancer cells.
AB  - Zinc at cytotoxic concentrations has been shown to regulate gene transcription in
      cancer cells, though zinc's involvement in posttranscriptional regulation is less
      characterized. In this study, we investigated the involvement of cytotoxic zinc
      in the posttranscriptional steps of gene expression. Clioquinol, a well
      established zinc ionophore, was used to raise intracellular zinc to reported
      cytotoxic levels. The MCF-7 human cancer cell line was applied as a cell model
      system. Several parameters were used as indictors of posttranscriptional
      regulation, including p-body formation, microRNA profiling, expression level of
      proteins known to regulate mRNA degradation, microRNA processing, and protein
      translation. p-body formation was observed in MCF-7 cells using several molecules
      known as p-body components. Clioquinol plus zinc enhanced p-body assembly in MCF
      7 cells. This enhancement was zinc-specific and could be blocked by a high
      affinity zinc chelator. The enhancement does not seem to be due to a stress
      response, as paclitaxel, a commonly used chemotherapeutic, did not cause enhanced
      p-body formation at a highly cytotoxic concentration. microRNA profiling
      indicated that clioquinol plus zinc globally down-regulates microRNA expression
      in this model system, which is associated with the reduced expression of Dicer,
      an enzyme key to microRNA maturation, and Ago2, a protein essential for microRNA
      stability. This study demonstrates that ionophoric zinc can induce cytotoxicity
      in cancer cells by globally regulating posttranscriptional events.

PMID- 22415088
TI  - Indomethacin activates protein kinase C and potentiates alpha7 ACh receptor
      responses.
AB  - BACKGROUND/AIMS: We have earlier found that indomethacin activates CaMKII, as a
      novel action distinct from COX inhibition. To explore further indomethacin
      actions, the present study focused upon PKC and examined the effect of
      indomethacin on alpha7 ACh receptor responses and hippocampal synaptic
      transmission through PKC. METHODS: We recorded currents through alpha7 ACh
      receptors expressed in Xenopus oocytes, quantified PKC activity in the in situ
      and cell-free PKC assay, and monitored field excitatory postsynaptic potentials
      (fEPSPs) and miniature excitatory postsynaptic currents (mEPSCs) from the CA1
      region of rat hippocampal slices. RESULTS: Indomethacin potentiated alpha7 ACh
      receptor currents in a bell-shaped concentration (100 nM-1 mM)-dependent manner,
      and the potentiating effect was inhibited by the PKC inhibitor GF109203X.
      Indomethacin activated PKC in a concentration (1-100 MUM)-dependent manner for
      cultured rat hippocampal neurons. Additionally, indomethacin (100 MUM)
      significantly activated PKC-epsilon under the cell-free conditions. Indomethacin
      (100 MUM) induced a transient huge increase in the fEPSP slope followed by
      persistent increase, and the former effect was attenuated by the alpha7 ACh
      receptor antagonist alpha-bungarotoxin or GF109203X. Indomethacin (100 MUM) also
      increased the rate of nicotine-evoked mEPSCs, and the effect was prevented by
      alpha-bungarotoxin or GF109203X. CONCLUSION: The results of the present study
      show that indomethacin activates PKC, possibly PKC-e in the brain, thereby
      potentiating alpha7 ACh receptor responses to stimulate presynaptic glutamate
      release, which in part contributes to facilitation of hippocampal transmission.
      This extends our knowledge about diverse indomethacin actions.

PMID- 22415089
TI  - Functional effects of nanoparticle exposure on Calu-3 airway epithelial cells.
AB  - High concentrations of manufactured carbon nanoparticles (CNP) are known to cause
      oxidative stress, inflammatory responses and granuloma formation in respiratory
      epithelia. To examine the effects of lower, more physiologically relevant
      concentrations, the human airway epithelial cell line, Calu-3, was used to
      evaluate potential alterations in transepithelial permeability and cellular
      function of airway epithelia after exposure to environmentally realistic
      concentrations of carbon nanoparticles. Three common carbon nanoparticles,
      fullerenes, single- and multi-wall carbon nanotubes (SWCNT, MWCNT) were used in
      these experiments. Electrophysiological measurements were performed to assay
      transepithelial electrical resistance (TEER) and epinephrine-stimulated chloride
      (Cl(-)) ion secretion of epithelial cell monolayers that had been exposed to
      nanoparticles for three different times (1 h, 24 h and 48 h) and over a 7 log
      unit range of concentrations. Fullerenes did not have any effect on the TEER or
      stimulated ion transport. However, the carbon nanotubes (CNT) significantly
      decreased TEER and inhibited epinephrine-stimulated Cl(-) secretion. The changes
      were time dependent and at more chronic exposures caused functional effects which
      were evident at concentrations substantially lower than have been previously
      examined. The functional changes manifested in response to physiologically
      relevant exposures would inhibit mucociliary clearance mechanisms and compromise
      the barrier function of airway epithelia.

PMID- 22415090
TI  - Lipopolysaccharide-induced cyclooxygenase-2 expression in mouse transformed Clara
      cells.
AB  - BACKGROUND/AIMS: Exacerbation of innate immune responses can contribute to
      development of acute lung injury. Multiple cell populations, including the
      bronchiolar epithelium, coordinate these inflammatory responses. Clara cells, non
      ciliated epithelial cells, are located in the distal airways in humans and
      conducting airways in mice. These cells actively participate in innate immune
      responses but their precise contributions remain poorly defined. METHODS: To test
      the hypothesis that E. coli lipopolysaccaride (LPS) treatment stimulates
      production of pro-inflammatory mediators in mouse transformed Clara cells (MTCC),
      MTCC were treated with E. coli lipopolysaccaride (LPS). RESULTS: LPS increased
      COX-2 expression and stimulated production of prostaglandins, including
      prostaglandin E(2) (PGE(2)). Enhanced mitogen activated protein kinase (MAPK)
      activation, nuclear factor-kappaB (NFkappaB) activation, and chemokine production
      were observed in MTCC in response to LPS treatment. CONCLUSIONS: While the role
      for Clara cells in the regulation of host defense and the progression of acute
      lung injury needs further characterization, our data suggests the importance of
      this unique cell population in the pathogenesis of LPS-induced acute lung injury.

PMID- 22415091
TI  - Nuclear transport of Wilms' tumour protein Wt1 involves importins alpha and beta.
AB  - BACKGROUND/AIMS: Wilms' tumour protein, Wt1, is a zinc finger molecule, which is
      required for normal embryonic development. Mutations of the WT1 gene can give
      rise to childhood cancer of the kidneys. Different Wt1 isoforms exist, which
      function either as transcription factors or have a presumed role in mRNA
      processing. Previous studies suggested that Wt1 undergoes nucleocytoplasmic
      shuttling, and cytoplasmic Wt1 was higher in malignant than in normal cells. The
      aim of this study was to analyse the molecular pathways along which Wt1 shuttles
      between the cytoplasm and nucleus. METHODS: Interaction of Wt1 protein with
      various importin alpha subtypes and importin beta was assessed in pull-down
      assays and co-immunoprecipitation experiments. Nuclear localisation signals (NLS)
      were identified by combining site-directed mutagenesis with subcellular
      immunodetection of the transfected Wt1 variants. RESULTS: Wt1(+/-KTS) proteins
      were found to interact with importin alpha1 and importin beta in vitro and in
      living cells in vivo. A NLS that was necessary and sufficient for nuclear import
      could be mapped to the third Wt1 zinc finger. Mutation of this NLS strongly
      weakened binding of Wt1 to importins. CONCLUSION: Nuclear translocation of Wilms'
      tumour protein involves importins alpha and beta, and a NLS in the third zinc
      finger.

PMID- 22415092
TI  - Tumor cell-educated periprostatic adipose tissue acquires an aggressive cancer
      promoting secretory profile.
AB  - BACKGROUND/AIMS: The microenvironment produces important factors that are crucial
      to prostate cancer (PCa) progression. However, the extent to which the cancer
      cells stimulate periprostatic adipose tissue (PPAT) to produce these proteins is
      largely unknown. Our purpose was to determine whether PCa cell-derived factors
      influence PPAT metabolic activity. METHODS: Primary cultures of human PPAT
      samples from PCa patients (adipose tissue organotypic explants and primary
      stromal vascular fraction, SVF) were stimulated with conditioned medium (CM)
      collected from prostate carcinoma (PC3) cells. Cultures without CM were used as
      control. We used multiplex analysis and ELISA for protein quantification, qPCR to
      determine mitochondrial DNA (mtDNA) copy number and zymography for matrix
      metalloproteinase activity, in order to evaluate the response of adipose tissue
      explants and SVFs to PC3 CM. RESULTS: Stimulation of PPAT explants with PCa PC3
      CM induced adipokines associated with cancer progression (osteopontin, tumoral
      necrosis factor alpha and interleukin-6) and reduced the expression of the
      protective adipokine adiponectin. Notably, osteopontin protein expression was 13
      fold upregulated. Matrix metalloproteinase 9 activity and mitochondrial DNA copy
      number were higher after stimulation with cancer CM. Stromovascular cells from
      PPAT in culture were not influenced by tumor-derived factors. CONCLUSION: The
      modulation of adipokine expression by tumor CM indicates the pervasive extent to
      which tumor cells command PPAT to produce factors favorable to their
      aggressiveness.

PMID- 22415093
TI  - PDGF-D/PDGF-betabeta receptor-regulated chemotaxis of malignant mesothelioma
      cells.
AB  - BACKGROUND/AIMS: Our earlier study suggested that platelet-derived growth factor
      (PDGF)- betabeta receptor regulates chemotaxis of human malignant mesothelioma
      cells such as MSTO-211H, NCIH-2052, NCIH-2452, and NCIH-28 cells, but not non
      malignant Met5A cells. The present study was designed to gain further insight
      into the PDGF-betabeta receptor signals underlying the chemotaxis. METHODS: PDGF
      D secreted from cells, activation of Akt and ERK, and cell migration were
      monitored for cells with and without knocking-down PDGF-betabeta receptor.
      RESULTS: FBS significantly stimulated PDGF-D secretion from malignant
      mesothelioma cells, but not Met5A cells. PDGF-D activated Akt and ERK in both the
      non-malignant and malignant cells. PDGF-D significantly facilitated migration of
      malignant mesothelioma cells, but not Met5A cells, with the extent varying among
      the cell types. The facilitatory action of PDGF-D was clearly prevented by
      knocking-down PDGF-betabeta receptor or inhibitors of PI3 kinase, PDK1, Akt,
      Rac1, ROCK, and MEK. CONCLUSION: The results of the present study indicate that
      PDGF-D promotes malignant mesothelioma cell chemotaxis through PDGF-betabeta
      receptor signaling pathways along a PI3 kinase/PDK1/Akt/Rac1/ROCK axis and
      relevant to ERK activation.

PMID- 22415094
TI  - Anticancer potential of 3-(arylideneamino)-2-phenylquinazoline-4(3H)-one
      derivatives.
AB  - Different quinazoline derivatives have showed wide spectrum of pharmacological
      activities. Some 3-(arylideneamino)-phenylquinazoline-4(3H)-ones have been
      reported to possess antimicrobial activity. The present study has been undertaken
      to evaluate the anticancer effect of these quinazolinone derivatives. The
      quinazolinone derivatives were synthesized as reported earlier. Compounds
      containing NO(2), OH, OCH(3), or OH and OCH(3) as substituent(s) on the
      arylideneamino group were named as P(3a), P(3b), P(3c), and P(3d) respectively.
      Out of these, P(3a) and P(3d) showed better cytotoxic activity than P(3b) and
      P(3c) on a panel of six cancer cell lines of different origin, namely, B16F10,
      MiaPaCa-2, HCT116, HeLa, MCF7, and HepG2, though the effect was higher in B16F10,
      HCT116, and MCF7 cells. P(3a) and P(3d) induced death of B16F10 and HCT116 cells
      was associated with characteristic apoptotic changes like cell shrinkage, nuclear
      condensation, DNA fragmentation, and annexin V binding. Also, cell cycle arrest
      at G1 phase, alteration of caspase-3, caspase-9, Bcl-2 and PARP levels, loss of
      mitochondrial membrane potential, and enhanced level of cytosolic cytochrome c
      were observed in treated B16F10 cells. Treatment with multiple doses of P(3a)
      significantly increased the survival rate of B16F10 tumor bearing BALB/c mice by
      suppressing the volume of tumor while decreasing microvascular density and
      mitotic index of the tumor cells.

PMID- 22415095
TI  - The effects of 17beta-estradiol on mitochondrial biogenesis and function in
      breast cancer cell lines are dependent on the ERalpha/ERbeta ratio.
AB  - BACKGROUND/AIMS: 17beta-estradiol (E2) is a risk factor for the development of
      breast cancer, and cause tumorigenesis in epithelial breast cells. Moreover, E2
      has distinct effects on different tissues that are attributed to the presence of
      two estrogen receptor isoforms, ERalpha and ERbeta. METHODS: The effect of E2 on
      mitochondrial biogenesis and function was investigated in two breast cancer cell
      lines with different estrogen receptor ratios, MCF-7 (high ERalpha/ERbeta ratio)
      and T47D (low ERalpha/ERbeta ratio) cell lines treated with physiological
      concentrations of E2 (1 nM). RESULTS: Mitochondria of the MCF-7 cell line showed
      an increase in proliferation but a decrease in functionality, while the T47D cell
      line, with low ERalpha/ERbeta ratio, maintained functionality with fewer
      mitochondria. CONCLUSION: Our results suggest that ERs endowment and its subtypes
      relation have an effect on treatment response and could contribute new ideas
      about mitochondria and ERs in breast cancer, as well as new indicators to the
      disease progression.

PMID- 22415096
TI  - Hypoxia-induced up-regulation of aquaporin-1 protein in prostate cancer cells in
      a p38-dependent manner.
AB  - BACKGROUND/AIMS: Aquaporin-1 (AQP1) is a glycoprotein that mediates osmotic water
      transport, its expression has been found to correlate with tumour stage in some
      tumours. However, the mechanism by which AQP1 protein expression is regulated in
      tumor cells remains to be fully elucidated. We hypothesized that hypoxia might
      play an important role in AQP1 induction during tumorigenesis and at the late
      stages of tumor development. METHODS: Isotonic and serum-free hypoxic models were
      used to investigate AQP1 expression in PC-3M human prostate cancer cells.
      RESULTS: AQP1 expression was up-regulated by density-induced pericellular hypoxia
      and cobalt(II) chloride (CoCl(2))-induced hypoxia at the transcriptional level.
      Moreover, phosphorylation of p38 mitogen-activated protein kinase (MAPK) was
      induced by density-induced pericellular hypoxia and CoCl(2)-induced hypoxia,
      specific inhibitors of p38 MAPK could concentration-dependently block those
      effects of hypoxia on AQP1 expression. Intracellular calcium ion (Ca(2+)) and
      protein kinase C (PKC) were shown to be responsible for the activation of p38
      MAPK pathway. In addition, AQP1 induction in dense cultures was dependent on
      lowered oxygen (O(2)) tension. In high cell density culture, certain secretory
      proteins might induce AQP1 expression indirectly. CONCLUSION: These findings
      suggest that AQP1 could be induced by hypoxia at transcription level, and the
      regulation of AQP1 in PC-3M cells is dependent on calcium, PKC and p38 MAPK, as
      well as low oxygen tension.

PMID- 22415097
TI  - A novel anticancer agent, SKLB70359, inhibits human hepatic carcinoma cells
      proliferation via G0/G1 cell cycle arrest and apoptosis induction.
AB  - Hepatocellular carcinoma is one of the most common cancers in worldwide. We
      previously reported a novel thienopyridine derivative 3-amino-6-(3,4
      dichlorophenyl) thieno[2,3-b]pyridine-2-carboxamide (SKLB70359) which possesses
      anticancer activity against hepatocellular carcinoma. In present study, we
      further investigated its anticancer activity and possible mechanism. The
      SKLB70359 treatment decreased the viability of a panel of hepatocellular
      carcinoma cell lines in a concentration- and time-dependent manner with IC(50)
      0.4 ~ 2.5 MUM. The mechanism study showed that SKLB70359 induced G0/G1 cell cycle
      arrest and then led to apoptotic cell death of HepG2 cell. The SKLB70359 induced
      G0/G1 cell cycle arrest was characterized by down-regulation of cyclin-dependent
      kinase 2 (CDK2), CDK4, CDK6 expression and up-regulation of p53, p21(WAF1).
      Activating of caspase-3 and caspase-9 was also observed. Meanwhile, proliferation
      inhibitory effect of SKLB70359 was associated with decreased level of
      phosphorylated p44/42 mitogen activated protein kinase (p44/42 MAPK) and
      phosphorylated retinoblastoma protein (Rb). Moreover, SKLB70359 exhibit less
      toxicity to non-cancer cells than tumor cells. In conclusion, the findings in
      this study suggested that SKLB70359 have potential anticancer efficacy via G0/G1
      cell cycle arrest and apoptosis induction. Its potential to be a candidate of
      anticancer agent is worth being further investigated.

PMID- 22415098
TI  - WNK3-SPAK interaction is required for the modulation of NCC and other members of
      the SLC12 family.
AB  - The serine/threonine with no lysine kinase 3 (WNK3) modulates the activity of the
      electroneutral cation-coupled chloride cotransporters (CCC) to promote Cl(-)
      influx and prevent Cl(-) efflux, thus fitting the profile for a putative "Cl(-)
      sensing kinase". The Ste20-type kinases, SPAK/OSR1, become phosphorylated in
      response to reduction in intracellular chloride concentration and regulate the
      activity of NKCC1. Several studies have now shown that WNKs function upstream of
      SPAK/OSR1. This study was designed to analyze the role of WNK3-SPAK interaction
      in the regulation of CCCs with particular emphasis on NCC. In this study we used
      the functional expression system of Xenopus laevis oocytes to show that different
      SPAK binding sites in WNK3 ((241, 872, 1336)RFxV) are required for the kinase to
      have effects on CCCs. WNK3-F1337A no longer activated NKCC2, but the effects on
      NCC, NKCC1, and KCC4 were preserved. In contrast, the effects of WNK3 on these
      cotransporters were prevented in WNK3-F242A. The elimination of F873 had no
      consequence on WNK3 effects. WNK3 promoted NCC phosphorylation at threonine 58,
      even in the absence of the unique SPAK binding site of NCC, but this effect was
      abolished in the mutant WNK3-F242A. Thus, our data support the hypothesis that
      the effects of WNK3 upon NCC and other CCCs require the interaction and
      activation of the SPAK kinase. The effect is dependent on one of the three
      binding sites for SPAK that are present in WNK3, but not on the SPAK binding
      sites on the CCCs, which suggests that WNK3 is capable of binding both SPAK and
      CCCs to promote their phosphorylation.

PMID- 22415099
TI  - KCC2a expression in a human fetal lens epithelial cell line.
AB  - The fetal human lens epithelial cell (LEC) line (FHL124) possesses all four
      K(+)Cl(-) (KCC) cotransporter isoforms, KCC1-4, despite KCC2 being typically
      considered a neuronal isoform. Since at least two spliced variants, KCC2a and
      KCC2b, are co-expressed in cells of the central nervous system, this study sought
      to define the KCC2 expression profile in FHL124 cells. KCC2a, but not KCC2b
      transcripts were detected by reverse transcriptase polymerase chain reaction (RT
      PCR). Proteins of molecular weights ranging from 95 to 135 kDa were found by
      Western blotting using non-variant specific anti-KCC2 antibodies directed against
      two different regions of the KCC2 proteins, and by biotinylation suggesting
      membrane expression. Immunofluorescence revealed membrane and punctate
      cytoplasmic staining for KCC2. Low levels of cytosolic alphaA and alphaB
      crystallines, and neuron-specific enolase were also detected contrasting with the
      strong membrane immunofluorescence staining for the Na/K ATPase alpha1 subunit.
      Since the lack of neuron-specific expression of the KCC2b variant in non-neuronal
      tissues has been proposed under control of a neuron-restrictive silencing element
      in the KCC2 gene, we hypothesize that this control may be lifted for the KCC2a
      variant in the FHL124 epithelial cell culture, a non-neuronal tissue of
      ectodermal origin.

PMID- 22415100
TI  - Synthesis and characterization of novel chiral NHC-palladium complexes and their
      application in copper-free Sonogashira reactions.
AB  - A new series of chiral N-heterocyclic carbene (NHC) palladium complexes were
      synthesized from a relatively inexpensive amino acid, l-phenylalanine. All these
      compounds were fully characterized by (1)H-NMR, (13)C-NMR and elemental analysis.
      The X-ray molecular structures of two of the complexes were reported. The
      catalytic activity of the four palladium complexes was successfully tested in the
      Sonogashira reaction under copper free conditions in air. The palladium complex
      3a provided good activity in the Sonogashira coupling reaction.

PMID- 22415101
TI  - Effect of multiple set on intramuscular metabolic stress during low-intensity
      resistance exercise with blood flow restriction.
AB  - Our previous study reported that intramuscular metabolic stress during low
      intensity resistance exercise was significantly enhanced by combining blood flow
      restriction (BFR); however, they did not reach the levels achieved during high
      intensity resistance exercise. That study was performed using a single set of
      exercise; however, usual resistance exercise consists of multiple sets with rest
      intervals. Therefore, we investigated the intramuscular metabolic stress during
      multiple-set BFR exercises, and compared the results with those during multiple
      set high-intensity resistance exercise. Twelve healthy young subjects performed 3
      sets of 1-min unilateral plantar flexion (30 repetitions) with 1-min intervals
      under 4 different conditions: low intensity (L, 20% 1 RM) and high intensity (H,
      65% 1 RM) without BFR, and L with intermittent BFR (IBFR, only during exercise)
      and with continuous BFR (CBFR, during rest intervals as well as exercise).
      Intramuscular metabolic stress, defined as intramuscular metabolites and pH, and
      muscle fiber recruitment were evaluated by 31P-magnetic resonance spectroscopy.
      The changes of intramuscular metabolites and pH during IBFR were significantly
      greater than those in L but significantly lower than those in H. By contrast,
      those changes in CBFR were similar to those in H. Moreover, the fast-twitch fiber
      recruitment, evaluating by a splitting Pi peak, showed a similar level to H. In
      conclusion, the multiple sets of low-intensity resistance exercise with
      continuous BFR could achieve with the same metabolic stress as multiple sets of
      high-intensity resistance exercise.

PMID- 22415102
TI  - Short-term creatine supplementation decreases reactive oxygen species content
      with no changes in expression and activity of antioxidant enzymes in skeletal
      muscle.
AB  - The effect of short-term creatine (Cr) supplementation upon content of skeletal
      muscle-derived-reactive oxygen species (ROS) was investigated. Wistar rats were
      supplemented with Cr (5 g/kg BW) or vehicle, by gavage, for 6 days. Soleus and
      extensor digitorum longus (EDL) muscles were removed and incubated for evaluation
      of ROS content using Amplex-UltraRed reagent. The analysis of expression and
      activity of antioxidant enzymes (superoxide dismutase 1 and 2, catalase and
      glutathione peroxidase) were performed. Direct scavenger action of Cr on
      superoxide radical and hydrogen peroxide was also investigated. Short-term Cr
      supplementation attenuated ROS content in both soleus and EDL muscles (by 41 and
      33.7%, respectively). Cr supplementation did not change expression and activity
      of antioxidant enzymes. Basal TBARS content was not altered by Cr
      supplementation. In cell-free experiments, Cr showed a scavenger effect on
      superoxide radical in concentrations of 20 and 40 mM, but not on hydrogen
      peroxide. These results indicate that Cr supplementation decreases ROS content in
      skeletal muscle possibly due to a direct action of Cr molecule on superoxide
      radical.

PMID- 22415103
TI  - Zwitterionic clusters with dianion core produced by electrospray ionisation of
      Bronsted acidic ionic liquids.
AB  - New Bronsted acidic ionic liquids (BAILs) are prepared by treating zwitterions,
      which are composed of an imidazolium cation and a sulfonate anion, with an
      alkanedisulfonic acid. Acidification of the zwitterions produces the cation and
      deprotonation of the alkanedisulfonic acid forms the anion of the new BAILs.
      Direct laser desorption/ionisation (LDI), matrix-assisted LDI (MALDI) and
      electrospray ionisation (ESI) are employed to transfer ions into the gas-phase
      for detection by mass spectrometry and for dissociation studies by tandem mass
      spectrometry. The components of the BAILs are confirmed by LDI and MALDI by the
      detection of the respective cation and anion and by ESI by the observation of the
      cation and the dianion. A prominent feature of ESI is the formation of aggregates
      (cluster ions). Positively charged cluster ions are formally composed of multiple
      zwitterions plus one additional proton. In the negative-ion mode the clusters
      also incorporate the zwitterions which are, however, linked with the
      alkanedisulfonate dianion. In collision-induced dissociations (CID), the cationic
      aggregates show the evaporation of zwitterions until the protonated zwitterion is
      reached. Similarly, the cluster dianions release zwitterions until the free
      alkane disulfonate dianion is reached. However, the 1:1 adduct of dianion and
      zwitterion also displays proton transfer and Coulomb explosion into the mono
      protonated disulfonic mono-anion and an imidazole-based carbene with sulfonate
      mono-anion.

PMID- 22415104
TI  - Adaptive microclimatic evolution of the dehydrin 6 gene in wild barley at
      "Evolution Canyon", Israel.
AB  - Dehydrins are one of the major stress-induced gene families, and the expression
      of dehydrin 6 (Dhn6) is strictly related to drought in barley. In order to
      investigate how the evolution of the Dhn6 gene is associated with adaptation to
      environmental changes, we examined 48 genotypes of wild barley, Hordeum
      spontaneum, from "Evolution Canyon" at Mount Carmel, Israel. The Dhn6 sequences
      of the 48 genotypes were identified, and a recent insertion of 342 bp at 5'UTR
      was found in the sequences of 11 genotypes. Both nucleotide and haplotype
      diversity of single nucleotide polymorphism in Dhn6 coding regions were higher on
      the AS ("African" slope or dry slope) than on the ES ("European" slope or humid
      slope), and the applied Tajima D and Fu-Li test rejected neutrality of SNP
      diversity. Expression analysis indicated that the 342 bp insertion at 5'UTR was
      associated with the earlier up-regulation of Dhn6 after dehydration. The genetic
      divergence of amino acids sequences indicated significant positive selection of
      Dhn6 among the wild barley populations. The diversity of Dhn6 in microclimatic
      divergence slopes suggested that Dhn6 has been subjected to natural selection and
      adaptively associated with drought resistance of wild barley at "Evolution
      Canyon".

PMID- 22415106
TI  - Clinical appraisal of endoscopy with narrow-band imaging system in the evaluation
      and management of homogeneous oral leukoplakia.
AB  - PURPOSE: To evaluate the clinical usefulness of endoscopy with a narrow-band
      imaging (NBI) system for the evaluation and management of homogeneous oral
      leukoplakia. METHODS: The chart records, morphology of vascular architecture of
      NBI, and histopathology of patients with homogeneous leukoplakia were
      retrospectively reviewed and analyzed. RESULTS: A total of 160 patients, with an
      average age of 50.96 +/- 10.25 years, were enrolled. In 35 cases of thin
      leukoplakia, only intraepithelium papillary capillary loop (IPCL) type I was
      shown by NBI, and only squamous hyperplasia was revealed pathologically. In 125
      cases of thick leukoplakia, IPCL type I was found in 94, IPCL type II in 29, and
      IPCL type III in 2. The Kendall rank correlation between pathology and NBI images
      was significant (p < 0.0001). CONCLUSIONS: The dichotomous classification of
      homogeneous leukoplakia by NBI is meaningful, and endoscopy with the NBI system
      is a promising tool for the evaluation and management of homogeneous oral
      leukoplakia.

PMID- 22415107
TI  - Effect of physical activity on functional performance and knee pain in patients
      with osteoarthritis :  analysis with marginal structural models.
AB  - BACKGROUND: A previous analysis of the Osteoarthritis Initiative study reported a
      dose-response relationship between physical activity and improved physical
      function in adults with knee osteoarthritis, using conventional statistical
      methods. These methods are subject to bias when confounders are affected by prior
      exposure. METHODS: We used baseline and 1-, 2-, and 3-year follow-up data from
      the Osteoarthritis Initiative study of 2545 US adults with knee osteoarthritis
      recruited between 2004 and 2006 from 4 clinical sites. Physical activity was
      measured using the Physical Activity Scale for the Elderly, and outcomes were
      functional performance measured by the timed 20-meter walk test and self-reported
      knee pain measured by the Western Ontario and McMaster Universities
      Osteoarthritis Index. We estimated the effect of physical activity on each
      outcome using inverse probability-weighted (IPW) estimators of marginal
      structural models. For each outcome, we fitted 2 separate IPW models adjusting
      for concurrent or lagged confounders. RESULTS: The mean differences in walking
      speed for the second, third, and fourth quartiles of physical activity relative
      to the first were 0.48 (95% confidence interval = -0.12 to 1.08), 0.45 (-0.23 to
      1.13), and 0.46 (-0.29 to 1.22) meters/min based on the IPW model adjusting for
      concurrent confounders. When adjusting for lagged confounders, the results were
      1.35 (0.64 to 2.07), 1.33 (0.54 to 2.14), and 1.26 (0.40 to 2.12). Both IPW
      models indicated that physical activity did not affect knee pain. CONCLUSIONS:
      Physical activity has no effect on knee pain and may have either a very small
      effect or no effect on functional performance in adults with knee osteoarthritis.

PMID- 22415108
TI  - Folic acid use and nonsyndromic orofacial clefts in China: a prospective cohort
      study.
AB  - BACKGROUND: Questions remain about the effectiveness, dose, and timing of folic
      acid in preventing orofacial clefts. Case-control studies report conflicting
      results. There have been no cohort studies of orofacial clefts and the use of
      folic acid without other vitamins. METHODS: In a prospective cohort of 240,244
      women enrolled between 1993 and 1995 in 1 northern and 2 southern provinces in
      China, we examined the risk of nonsyndromic cleft lip with or without cleft
      palate (CL/P) and cleft palate alone (CP) in relation to maternal use of 400 MUg
      of folic acid without other vitamins. RESULTS: Daily use of 400 MUg of folic acid
      without other vitamins, started before the last menstrual period (LMP), was
      associated with reduced risk of CL/P with adjusted rate ratio (aRR) of 0.69 (95%
      confidence interval = 0.55-0.87). The greatest reduction in risk was observed in
      the north among daily users who began taking folic acid pills before LMP (aRR =
      0.21 [0.10-0.44]); in the south there was marginal reduction in risk (aRR = 0.81
      [0.63-1.05]). No evidence of reduced CL/P risk was observed among women who
      started folic acid pills on or after their LMP. No persuasive evidence for
      reduction in CP risk was seen with folic acid pill use at any time. CONCLUSION:
      Daily maternal consumption of 400 MUg of folic acid without other vitamins,
      started before mother's LMP, was associated with a reduced risk of CL/P in babies
      born in a high-prevalence region of China.

PMID- 22415109
TI  - Socioeconomic position and lung cancer risk: how important is the modeling of
      smoking?
AB  - BACKGROUND: Although it has been reported that low socioeconomic position (SEP)
      is associated with lung cancer, the extent to which this reflects SEP differences
      in cigarette smoking is unclear. We investigated how various modeling approaches
      for smoking might influence this observed association. METHODS: We used data from
      a case-control study conducted in Montreal, Canada (1996-2002), comprising 1203
      subjects with incident lung cancer and 1513 population controls. SEP was measured
      by census-based and self-reported income, residential value, education level, and
      occupational class. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      estimated using logistic regression, and Akaike's Information Criterion (AIC) was
      used to compare model fit. RESULTS: Associations were observed between SEP
      indicators and lung cancer, but gradually disappeared with more comprehensive
      adjustment for smoking. For comparisons of the highest to lowest categories of
      census-based income, the OR for lung cancer was 0.58 (95% CI = 0.32-1.05) when
      adjusting only for smoking status (never, former, current), but 0.97 (0.51-1.86)
      when adjusting for smoking status, cigarette-years, and time since cessation. For
      comparisons of highest to lowest levels of education, the ORs for lung cancer
      were 0.50 (0.38-0.65) and 0.76 (0.57-1.02), when making the least and most
      comprehensive adjustments for smoking, respectively. Similarly, comparing highly
      skilled with unskilled manual workers, the ORs were 0.78 (0.54-1.12) and 1.00
      (0.68-1.47), respectively. With thorough smoking adjustment, associations between
      SEP indicators and lung cancer virtually disappeared, and SEP did not improve
      model fit. CONCLUSIONS: Previously reported associations of SEP with lung cancer
      may be attributable to incomplete adjustment for smoking. Our findings underline
      the importance of adjusting for several dimensions of smoking behavior to make
      correct inferences.

PMID- 22415110
TI  - Long-term dietary cadmium intake and cancer incidence.
AB  - BACKGROUND: Cadmium, a ubiquitous environmental pollutant, is classified as a
      carcinogenic substance. Several laboratory and epidemiologic studies of workers
      and subjects in polluted areas have suggested a positive association between
      cadmium exposure and risk of several cancers. However, data from general
      populations are sparse. We prospectively examined the association between cadmium
      exposure and incidence of cancer in a Japanese population with a relatively high
      dietary intake of cadmium. METHODS: We conducted a population-based prospective
      study in 90,383 Japanese men and women 45-74 years of age. Participants responded
      to a validated questionnaire that included 138 food items. We estimated dietary
      cadmium intake from 6 food groups, based on the questionnaire data. During 9
      years of follow-up, 5849 cancer cases were identified. Hazard ratios (HRs) and
      95% confidence intervals (CIs) for cancer were calculated by Cox proportional
      hazards modeling. RESULTS: There was no evidence of an association of cadmium
      consumption and total cancer, with HRs in the highest versus lowest cadmium
      intake group of 0.94 (95% CI = 0.82 to 1.08; test for trend, P = 0.46) for men
      and 0.96 (0.81 to 1.15; 0.60) for women. No site-specific cancers were associated
      with cadmium intake in men or women. CONCLUSION: We found no associations of
      cancer with cadmium, at least at the exposure levels observed in a general
      population in Japan.

PMID- 22415111
TI  - Major life events as potential triggers of sudden cardiac arrest.
AB  - BACKGROUND: We investigated the risk of sudden cardiac arrest in association with
      the recent loss of, or separation from, a family member or friend. METHODS: Our
      case-crossover study included 490 apparently healthy married residents of King
      County, Washington, who suffered sudden cardiac arrest between 1988 and 2005. We
      compared exposure to spouse-reported family/friend events occurring <= 1 month
      before sudden cardiac arrest with events occurring in the previous 5 months. We
      evaluated potential effect modification by habitual vigorous physical activity.
      RESULTS: Recent family/friend events were associated with a higher risk of sudden
      cardiac arrest (odds ratio [OR] = 1.6; 95% confidence interval [CI] = 1.1-2.4).
      ORs for cases with and without habitual vigorous physical activity were 1.1 (0.6
      2.2) and 2.0 (1.2-3.1), respectively (interaction P = 0.02). CONCLUSIONS: These
      results suggest family/friend events may trigger sudden cardiac arrest and raise
      the hypothesis that habitual vigorous physical activity may lower susceptibility
      to these potential triggers.

PMID- 22415112
TI  - Quantitative imaging biomarkers: the application of advanced image processing and
      analysis to clinical and preclinical decision making.
AB  - The importance of medical imaging for clinical decision making has been steadily
      increasing over the last four decades. Recently, there has also been an emphasis
      on medical imaging for preclinical decision making, i.e., for use in
      pharamaceutical and medical device development. There is also a drive towards
      quantification of imaging findings by using quantitative imaging biomarkers,
      which can improve sensitivity, specificity, accuracy and reproducibility of
      imaged characteristics used for diagnostic and therapeutic decisions. An
      important component of the discovery, characterization, validation and
      application of quantitative imaging biomarkers is the extraction of information
      and meaning from images through image processing and subsequent analysis.
      However, many advanced image processing and analysis methods are not applied
      directly to questions of clinical interest, i.e., for diagnostic and therapeutic
      decision making, which is a consideration that should be closely linked to the
      development of such algorithms. This article is meant to address these concerns.
      First, quantitative imaging biomarkers are introduced by providing definitions
      and concepts. Then, potential applications of advanced image processing and
      analysis to areas of quantitative imaging biomarker research are described;
      specifically, research into osteoarthritis (OA), Alzheimer's disease (AD) and
      cancer is presented. Then, challenges in quantitative imaging biomarker research
      are discussed. Finally, a conceptual framework for integrating clinical and
      preclinical considerations into the development of quantitative imaging
      biomarkers and their computer-assisted methods of extraction is presented.

PMID- 22415113
TI  - Application of innovation economics to medical imaging and information systems
      technologies.

PMID- 22415114
TI  - A genetically encoded copper(I) sensor based on engineered structural distortion
      of EGFP.
AB  - We report a genetically encoded fluorescent sensor for in vivo copper(I) imaging
      based on engineered intramolecular mechanical strain and structural distortion of
      EGFP.

PMID- 22415115
TI  - REGgamma is a strong candidate for the regulation of cell cycle, proliferation
      and the invasion by poorly differentiated thyroid carcinoma cells.
AB  - REGgamma is a proteasome activator that facilitates the degradation of small
      peptides. Abnormally high expression of REGgamma has been observed in thyroid
      carcinomas. The purpose of the present study was to explore the role of REGgamma
      in poorly differentiated thyroid carcinoma (PDTC). For this purpose, small
      interfering RNA (siRNA) was introduced to down-regulate the level of REGgamma in
      the PDTC cell line SW579. Down-regulation of REGgamma at the mRNA and protein
      levels was confirmed by RT-PCR and Western blot analyses. FACS analysis revealed
      cell cycle arrest at the G1/S transition, the MTT assay showed inhibition of cell
      proliferation, and the Transwell assay showed restricted cell invasion.
      Furthermore, the expression of the p21 protein was increased, the expression of
      proliferating cell nuclear antigen (PCNA) protein decreased, and the expression
      of the p27 protein was unchanged as shown by Western blot analyses. REGgamma
      plays a critical role in the cell cycle, proliferation and invasion of SW579
      cells. The alteration of p21 and PCNA proteins related to the down-regulation of
      REGgamma suggests that p21 and PCNA participate in the process of REGgamma
      regulation of cell cycle progression and cell proliferation. Thus, targeting
      REGgamma has a therapeutic potential in the management of PDTC patients.

PMID- 22415116
TI  - Negative correlation between phospholipase and esterase activity produced by
      Fusarium isolates.
AB  - Fusarium species have emerged as one of the more outstanding groups of clinically
      important filamentous fungi, causing localized and life-threatening invasive
      infections with high morbidity and mortality. The ability to produce different
      types of hydrolytic enzymes is thought to be an important virulence mechanism of
      fungal pathogens and could be associated with the environment of the
      microorganism. Here, we have measured the production of two distinct lipolytic
      enzymes, phospholipase and esterase, by sixteen Fusarium isolates recovered from
      the hospital environment, immunocompromised patients' blood cultures, foot
      interdigital space scrapings from immunocompromised patients, and foot
      interdigital space scrapings from immunocompetent patients (4 isolates each).
      Fourteen of these 16 isolates were identified as Fusarium solani species complex
      (FSSC) and two were identified as F. oxysporum species complex (FOSC). Some
      relevant genus characteristics were visualized by light and electron microscopy
      such as curved and multicelled macroconidia with 3 or 4 septa, microconidia,
      phialides, and abundant chlamydospores. All Fusarium isolates were able to
      produce esterase and phospholipase under the experimental conditions. However, a
      negative correlation was observed between these two enzymes, indicating that a
      Fusarium isolate with high phospholipase activity has low esterase activity and
      vice versa. In addition, Fusarium isolated from clinical material produced more
      phospholipases, while environmental strains produced more esterases. These
      observations may be correlated with the different types of substrates that these
      fungi need to degrade during their nutrition processes.

PMID- 22415117
TI  - Pulsed ultrasound therapy accelerates the recovery of skeletal muscle damage
      induced by Bothrops jararacussu venom.
AB  - We studied the effect of pulsed ultrasound therapy (UST) and antibothropic
      polyvalent antivenom (PAV) on the regeneration of mouse extensor digitorum longus
      muscle following damage by Bothrops jararacussu venom. Animals (Swiss male and
      female mice weighing 25.0 +/- 5.0 g; 5 animals per group) received a perimuscular
      injection of venom (1 mg/kg) and treatment with UST was started 1 h later (1
      min/day, 3 MHz, 0.3 W/cm(2), pulsed mode). Three and 28 days after injection,
      muscles were dissected and processed for light microscopy. The venom caused
      complete degeneration of muscle fibers. UST alone and combined with PAV (1.0
      mL/kg) partially protected these fibers, whereas muscles receiving no treatment
      showed disorganized fascicules and fibers with reduced diameter. Treatment with
      UST and PAV decreased the effects of the venom on creatine kinase content and
      motor activity (approximately 75 and 48%, respectively). Sonication of the venom
      solution immediately before application decreased the in vivo and ex vivo
      myotoxic activities (approximately 60 and 50%, respectively). The present data
      show that UST counteracts some effects of B. jararacussu venom, causing
      structural and functional improvement of the regenerated muscle after venom
      injury.

PMID- 22415118
TI  - Time course of the hemodynamic responses to aortic depressor nerve stimulation in
      conscious spontaneously hypertensive rats.
AB  - The time to reach the maximum response of arterial pressure, heart rate and
      vascular resistance (hindquarter and mesenteric) was measured in conscious male
      spontaneously hypertensive (SHR) and normotensive control rats (NCR; Wistar; 18
      22 weeks) subjected to electrical stimulation of the aortic depressor nerve (ADN)
      under thiopental anesthesia. The parameters of stimulation were 1 mA intensity
      and 2 ms pulse length applied for 5 s, using frequencies of 10, 30, and 90 Hz.
      The time to reach the hemodynamic responses at different frequencies of ADN
      stimulation was similar for SHR (N = 15) and NCR (N = 14); hypotension = NCR
      (4194 +/- 336 to 3695 +/- 463 ms) vs SHR (3475 +/- 354 to 4494 +/- 300 ms);
      bradycardia = NCR (1618 +/- 152 to 1358 +/- 185 ms) vs SHR (1911 +/- 323 to 1852
      +/- 431 ms), and the fall in hindquarter vascular resistance = NCR (6054 +/- 486
      to 6550 +/- 847 ms) vs SHR (4849 +/- 918 to 4926 +/- 646 ms); mesenteric = NCR
      (5574 +/- 790 to 5752 +/- 539 ms) vs SHR (5638 +/- 648 to 6777 +/- 624 ms). In
      addition, ADN stimulation produced baroreflex responses characterized by a faster
      cardiac effect followed by a vascular effect, which together contributed to the
      decrease in arterial pressure. Therefore, the results indicate that there is no
      alteration in the conduction of the electrical impulse after the site of
      baroreceptor mechanical transduction in the baroreflex pathway (central and/or
      efferent) in conscious SHR compared to NCR.

PMID- 22415119
TI  - Forced to be right.
AB  - In "Forced to be Free", Neil Levy surveys the raft of documented decision-making
      biases that humans are heir to, and advances several bold proposals designed to
      enhance the patient's judgment. Gratefully, Levy is moved by the psychological
      research on judgment and decision-making that documents people's inaccuracy when
      identifying courses of action will best promote their subjective well-being. But
      Levy is quick to favour the patient's present preferences, to ensure they get
      "final say" about their treatment. I urge the opposite inclination, raising
      doubts about whether the patient's "present preferences" are the best expression
      of their "final say". When there is adequate evidence that people, by their own
      lights, overemphasize their present preferences about the future, we should
      carefully depreciate those preferences, in effect biasing them to make the right
      decision by their own lights. 

PMID- 22415120
TI  - Peer-to-peer nursing rounds and hospital-acquired pressure ulcer prevalence in a
      surgical intensive care unit: a quality improvement project.
AB  - We conducted a quality improvement project in order to evaluate the effect of
      nurse-to-nurse bedside "rounding" as a strategy to decrease hospital-acquired
      pressure ulcers (HAPU) in a surgical intensive care unit. We instituted weekly
      peer-to-peer bedside skin rounds in a 17-bed surgical intensive care unit. Two
      nurses were identified as skin champions and trained by the hospital's certified
      WOC nurse to conduct skin rounds. The skin champion nurses conducted weekly peer
      to-peer rounds that included discussions about key elements of our patients' skin
      status including current Braden Scale for Pressure Sore Risk score, and
      implementation of specific interventions related to subscale risk assessment. If
      a pressure ulcer was present, the current action plan was reevaluated for
      effectiveness. Quarterly HAPU prevalence studies were conducted from January 2008
      to December 2010. Nineteen patients experienced a HAPU: 17 were located on the
      coccyx and 2 on the heel. Ten ulcers were classified as stage II, 3 PU were stage
      IV, 5 were deemed unstageable, and 1 was classified as a deep tissue injury. The
      frequency of preventive interventions rose during our quality improvement
      project. Specifically, the use of prevention surfaces increased 92%,
      repositioning increased 30%, nutrition interventions increased 77%, and moisture
      management increased 100%. Prior to focused nursing rounds, the highest HAPU
      prevalence rate was 27%. After implementing focused nursing rounds, HAPU rates
      trended down and were 0% for 3 consecutive quarters.

PMID- 22415121
TI  - Context for WOC practice: special focus on preventing sacral pressure ulcers in
      the intensive care unit setting.

PMID- 22415122
TI  - Navigating the institutional review board in the wound, ostomy, and continence
      research process.

PMID- 22415123
TI  - Prophylactic dressing application to reduce pressure ulcer formation in cardiac
      surgery patients.
AB  - PURPOSE: The study was designed to determine if application of a self-adherent
      silicone border foam dressing would reduce pressure ulcer incidence when compared
      to standard preventive interventions among patients managed in a cardiac surgery
      intensive care unit (CSICU). SUBJECTS AND SETTING: One hundred consecutive
      patients in the CSICU at Virginia Commonwealth University Medical Center in
      Richmond participated in the study. Fifteen were subsequently excluded due to
      incomplete data or failure to remain in the CSICU for at least 48 hours. Of the
      100 subjects consecutively enrolled, 56 subjects were assigned to the
      intervention group with attrition of 6 subjects (6/56), and 39 were assigned to
      the standard care comparison group with attrition of 4 subjects (4/39). Five
      study forms were lost and the group assignment of those subjects is unknown.
      METHODS: Patients admitted to the CSICU were assigned to either standard
      treatment or an intervention group consisting of standard preventive care plus
      application of the silicone border foam dressing. The assignment of subjects to
      these groups was done in a nonrandom manner, via prestudy room designation (7
      intervention rooms/7 standard practice rooms) and room availability on call from
      the operating room. The charge nurse and bed management staff were unaware of
      room designation, and staff did not know which group the subjects were assigned
      to until they admitted the patient and opened the bedside chart that indicated
      group assignment. Twenty-one covariates were compared between the 2 groups. A Cox
      proportional hazards model was computed to compare the hazard (risk per unit
      time) of developing a pressure ulcer between these groups. Propensity score
      covariate adjustment was performed to adjust for any imbalance between the
      groups. RESULTS: Nine pressure ulcers developed during the course of the study.
      Eight pressure ulcers developed in 4 out of 35 patients who received standard
      preventive care; 5 were classified as suspected deep tissue injuries and 3 were
      classified as stage II pressure ulcers. One pressure ulcer developed in 1 out of
      50 patients in the intervention group; it was classified as suspected deep tissue
      injury. No statistically significant difference in any covariate was found
      between the groups (all P > .058). The group that received standard care had a
      hazard ratio of 3.6 in relation to the intervention group, but this difference
      was not statistically significant (P = .3). CONCLUSION: Pressure ulcer incidence
      was lower than anticipated over the study period for both groups. No
      statistically significant difference in pressure ulcer incidence between the
      intervention and control groups was found. A randomized controlled trial based on
      a power analysis is needed to more precisely determine the efficacy of a silicone
      border foam dressing for prevention of pressure ulcers in the intensive care
      unit.

PMID- 22415124
TI  - Reduction of sacral pressure ulcers in the intensive care unit using a silicone
      border foam dressing.
AB  - PURPOSE: We sought to determine if a silicone border foam dressing could decrease
      the incidence of sacral pressure ulcers in an intensive care unit. SUBJECTS AND
      SETTING: The study setting was an intensive care unit located in a 303-bed
      hospital with a designation of level 2 trauma. The unit specializes in the care
      of critically ill medical and postoperative adults. Two hundred seventy-three
      patients participated in the study; their mean age was 65 years (range, 18-105
      years). METHODS: Baseline sacral hospital-acquired pressure ulcer (HAPU)
      incidence was determined during a period of 35 months; skin care representatives
      examined all patients in our critical care unit for HAPUs on a monthly basis.
      Based on this baseline incidence, we studied the effect of application of a
      silicone-bordered foam dressing applied to the sacrum. The observation period for
      our study intervention was 6 months; the sacral area was examined twice daily
      during this period. RESULTS: The average baseline sacral HAPU prevalence during
      the 35-month observation was 13.6% as compared to an incidence of 1.8% during a 6
      month prospective study. Three of the 5 patients developed suspected deep tissue
      injuries and subsequently expired. The remaining 2 subjects developed stage 2
      pressure ulcers, one of whom also expired. CONCLUSION: Following application of a
      silicone-bordered foam dressing, we were able to achieve a HAPU of 1.8%.

PMID- 22415125
TI  - Use of a sacral silicone border foam dressing as one component of a pressure
      ulcer prevention program in an intensive care unit setting.
AB  - In 2008, patients in the intensive care unit (ICU) at Danbury Hospital, Danbury,
      Connecticut, experienced 79 pressure ulcers. As a result, pressure ulcer
      prevention interventions were standardized in critical care and medical-surgical
      units and education was provided to all direct patient care staff about
      principles of skin care and prevention. Following these efforts, 53 ICU patients
      developed pressure ulcers in the sacral area in fiscal year 2009, representing a
      12.5% incidence for the ICU as compared to a 3.4% overall pressure ulcer
      incidence for the total hospital. In order to achieve additional reduction in
      pressure ulcer incidence, we replicated an initiative that called for application
      of a silicone foam dressing every 3 days to determine its effect on sacral
      pressure ulcer incidence in the ICU. We found that the use of the dressing
      further diminished the incidence of sacral pressure ulcers in our patients.

PMID- 22415126
TI  - Studies on the use of silicone foam dressing for prevention of sacrococcygeal
      breakdown in high-risk patients.

PMID- 22415127
TI  - The relationship between spiritual well-being and psychosocial adjustment in
      Taiwanese patients with colorectal cancer and a colostomy.
AB  - PURPOSE: We examined relationships among demographic and clinical
      characteristics, spiritual well-being, and psychosocial adjustment in Taiwanese
      patients with colorectal cancer and a colostomy. DESIGN: A descriptive, cross
      sectional, exploratory study design was used to answer research questions.
      SUBJECTS AND SETTING: Participants were recruited from the outpatient ambulatory
      clinic in the gastrointestinal surgical department at the medical center of
      National Taiwan University. Forty-five Taiwanese patients aged 42 to 83 years who
      were diagnosed with colorectal cancer and underwent colostomy surgery
      participated in the study. METHODS: Participants completed a personal data
      questionnaire designed for this study, along with 2 validated instruments, the
      Spiritual Well-Being Scale and the Psychosocial Adjustment to Illness Scale-Self
      Report. FINDINGS: Forty-five persons participated in the study; 69% reported a
      moderate level of spiritual well-being. Participants reported strong adjustment
      to extended family relationships, but poor adjustment in sexual relationships.
      Spiritual well-being was significantly associated with psychosocial adjustment (r
      = -0.52, P < .01), and 4 predictors (income change after surgery, self-rated
      disease severity, time since surgery, and spiritual well-being) accounted for 53%
      of the variance in psychosocial adjustment. CONCLUSIONS: Spiritual well-being
      plays an important role for Taiwanese patients when faced with psychosocial
      adjustment related to life with colorectal cancer and a colostomy.

PMID- 22415129
TI  - Prospective longitudinal evaluation of quality of life in patients with permanent
      colostomy after curative resection for rectal cancer: a preliminary study.
AB  - PURPOSE: The aim of this study was to evaluate health-related quality of life in
      patients with a colostomy immediately before and during the first year after
      surgery. SUBJECTS AND SETTING: Patients (aged >=20 years) who were diagnosed with
      rectal cancer and scheduled to undergo curative surgery with a permanent
      colostomy were recruited for this study. Data were collected at 2 university
      hospitals in Tokyo. METHODS: Participants were asked to complete a self
      administered questionnaire regarding health-related quality of life before
      surgery and a mailed or hand delivered questionnaire to evaluate quality of life
      at 2, 6, and 12 months after surgery using the Short Form-36 version 2. For
      patients who responded at all 4 time points, the scores at each time point were
      compared using paired t tests to examine longitudinal changes in quality of life
      after surgery. RESULTS: Mean quality-of-life scores in most domains before
      surgery and during the first year after surgery were lower than the normal
      control in the norm-based scoring method. Scores at 2 months after surgery were
      lower than those before surgery. At 12 months after surgery, however, quality-of
      life scores improved almost to the level observed before surgery, with the
      exception of the score in the social functioning domain. Statistical differences
      in scores between the time points of the survey were observed in the role
      physical, bodily pain, and mental health domains. CONCLUSIONS: These results
      suggest that patients with permanent colostomy after curative resection for
      rectal cancer need additional medical support and care before surgery and during
      the first year after surgery.

PMID- 22415130
TI  - WOC nurse consult: peristomal varices.

PMID- 22415131
TI  - Environmental cues to urgency and leakage episodes in patients with overactive
      bladder syndrome: a pilot study.
AB  - PURPOSE: To assess the frequency with which environmental cues, which might
      constitute Pavlovian-conditioned stimuli, occur with urgency and leakage symptoms
      associated with overactive bladder syndrome (OAB). SUBJECTS AND SETTINGS: The
      sample group comprised 17 adults (13 women and 4 men); their median age was 74.71
      years. METHODS: A semistructured interview was conducted with a convenience
      sample of 17 patients diagnosed with OAB. Patients were interviewed about
      interoceptive and environmental cues they related to instances of urinary urgency
      and leakage. Interviews persisted for 6.11 to 59.38 minutes (M = 21.86 minutes)
      and were conducted by an interviewer who was trained to administer the interview
      guide. RESULTS: Most respondents associated at least 1 environmental cue with
      urgency and leakage, respectively. A mean of 6.1 urgency-related and 4.0 leak
      related environmental cues were reported. The most commonly reported
      environmental cues were "on my way to the bathroom" reported by 88% and "opening
      the front door of my home" reported by 71%. CONCLUSION: These findings support
      the hypothesis that Pavlovian conditioning plays a role in OAB symptoms and
      suggest that treatment might be enhanced by inclusion of Pavlovian extinction
      procedures.

PMID- 22415132
TI  - Competence to provide urinary incontinence care in Taiwan's nursing homes:
      perceptions of nurses and nurse assistants.
AB  - PURPOSE: Nursing staff play an essential role in ensuring the quality of
      continence care in nursing homes. The purpose of this study was to describe the
      level of competence (knowledge, attitudes, and practice behaviors) of urinary
      incontinence (UI) care in nursing home staff in Taiwan. METHOD: A cross-sectional
      postal survey was used to gather self-reported data from an island-wide sample of
      195 nurses and 99 nurse assistants (NAs) in Taiwan. Participants completed the UI
      knowledge, the UI attitude, and the practice behaviors of UI care scales.
      RESULTS: The level of UI knowledge in nurses was higher than that of NAs,
      although nurses had less-positive attitudes than NAs. Reported practice behaviors
      of UI care did not differ between nurses and NAs. Changes of wet clothes, linens,
      and diapers were the most commonly reported practice behaviors. Information
      gathering, physical examination, and pelvic floor muscle exercises were performed
      less commonly in nursing homes. CONCLUSIONS: Knowledge and positive attitudes
      regarding UI need to be improved in both nurses and NAs in nursing homes. Several
      deficits were found in practice behaviors of UI care. A competency-based
      education approach is suggested to enable awareness of UI and cultural changes on
      individual and institutional levels.

PMID- 22415133
TI  - The certified foot care nurse and the importance of comprehensive foot
      assessments.

PMID- 22415134
TI  - Reepithelialization under pressure: a case study.
AB  - BACKGROUND: This case study describes the care of an obese male with a history of
      hypertension and venous insufficiency. CASE: The patient is a 55-year-old
      nonsmoker with clinical evidence of normal extremity arterial flow, who sustained
      a traumatic rupture of a venous varicosity on his left lateral calf while getting
      out of his car. Several months of wound care using standard compression
      strategies failed to result in wound closure. Drawing on a case study that
      described the management of a burn wound with silver hydrofiber, the patient was
      successfully managed with the same silver hydrofiber along with compression. This
      wound reepithelialized following application of a single dressing that remained
      in place under compression for a period of 2 weeks. After months of trial and
      failure, full healing was achieved within 4 weeks of initiating this treatment.
      CONCLUSION: Delivery of optimal care is based on the unique needs of the patient
      and available resources. This case illustrated how a published case study can be
      applied to the unique challenges of a second patient.

PMID- 22415136
TI  - Overexpression of IL-7 enhances cisplatin resistance in glioma.
AB  - Cisplatin is one of the most commonly used chemotherapeutic agents for glioma
      patients. In this study, array comparative genomic hybridization (aCGH) was used
      to identify genes associated with cisplatin resistance in a human glioma cell
      line. The cisplatin-resistant U251/CP2 cell line was derived by stepwise
      selection using cisplatin. The genetic aberrations of the U251 parental cell line
      and the U251/CP2 cells were analyzed using aCGH. RT-PCR was used to detect the
      expression of the altered genes revealed by aCGH. The sensitivity of glioma cells
      to cisplatin was determined by using the MTT assay. Apoptosis was detected using
      flow cytometry and western blot analysis. The IC 50 value of cisplatin in
      U251/CP2 cells was five times higher than its IC 50 in U251 cells. The U251 cells
      lost at least one copy each of the CFHR1 and CFHR3 genes, and both CFHR1 and
      CFHR3 were homozygously deleted in U251/CP2 cells. The U251/CP2 cells gained two
      to three copies of C8orf70 and IL-7 genes. IL-7 mRNA expression was studied in 12
      glioma cell lines, and expression was positively correlated with the IC 50 of
      cisplatin. Furthermore, IL-7 mRNA expression was also positively correlated with
      the IC 50 of cisplatin in 91 clinical glioma specimens. Additionally, treatment
      with recombinant human IL-7 (rhIL-7) enhanced cisplatin resistance and increased
      the relative growth rate of the glioma cells. Moreover, the apoptosis induced by
      cisplatin could be inhibited by IL-7. In conclusion, our results suggest that IL
      7 may play an important role in cisplatin resistance in glioma.

PMID- 22415137
TI  - Boswellic acid induces epigenetic alterations by modulating DNA methylation in
      colorectal cancer cells.
AB  - Accumulating evidence suggests that chemopreventive effects of some dietary
      polyphenols may in part be mediated by their ability to influence epigenetic
      mechanisms in cancer cells. Boswellic acids, derived from the plant Boswellia
      serrata, have long been used for the treatment of various inflammatory diseases
      due to their potent anti-inflammatory activities. Recent preclinical studies have
      also suggested that this compound has anti-cancer potential against various
      malignancies. However, the precise molecular mechanisms underlying their anti
      cancer effects remain elusive. Herein, we report that boswellic acids modulate
      DNA methylation status of several tumor suppressor genes in colorectal cancer
      (CRC) cells. We treated RKO, SW48 and SW480 CRC cell lines with the active
      principle present in boswellic acids, acetyl-keto-beta-boswellic acid (AKBA).
      Using genome-wide DNA methylation and gene expression microarray analyses, we
      discovered that AKBA induced a modest genome-wide demethylation that permitted
      simultaneous re-activation of the corresponding tumor suppressor genes. The
      quantitative methylation-specific PCR and RT-PCR validated the gene demethylation
      and re-expression in several putative tumor suppressor genes including SAMD14 and
      SMPD3. Furthermore, AKBA inhibited DNMT activity in CRC cells. Taken together,
      these results lend further support to the growing notion that anti-cancer effect
      of boswellic acids may in part be due to its ability to demethylate and
      reactivate methylation-silenced tumor suppressor genes. These results suggest
      that not only boswellic acid might be a promising epigenetic modulator in the
      chemoprevention and treatment of CRC, but also provide a rationale for future
      investigations on the usefulness of such botanicals for epigenetic therapy in
      other human malignancies.

PMID- 22415138
TI  - Multiple pharmacological actions of Yiqi Huatan Decoction in a model of
      depression in rats.
AB  - OBJECTIVE: To investigate the influence of Yiqi Huatan Decoction (, YHD) on a
      model of depression in rats under different pathological conditions. METHODS:
      Thirty-two male SD rats were randomly divided into 4 groups of 8: normal, model,
      YHD, and maprotiline. The model group, YHD group and maprotiline group used
      separate feeding and rats were exposed to chronic and unpredictable stress to
      build the depression model. From day 2, the YHD group and maprotiline group were
      respectively given YHD (7 g/kg) and maprotiline (10 mg/kg) by gastrogavage once
      daily. The normal and model groups were given the same volume of drinking water.
      The medication duration were 21 days. At the end of the experiment, the serum
      levels of copper and zinc were determined by atomic absorption spectroscopy,
      plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol (COR)
      were detected by radioimmunoassay, and levels of norepinephrine (NE), dopamine
      (DA), and 5-hydroxytryptamine (5-HT) in the hypothalamus were analysed by high
      performance liquid chromatography-eletricochemistry. RESULTS: Compared with the
      content of copper and zinc in the serum of rats in the normal group, serum copper
      levels in model rats were significantly increased and zinc content was
      significantly reduced (both P<0.05). Plasma concentrations of ACTH and COR in the
      model group were significantly increased compared with those in the normal group
      (P<0.05, P<0.01). The contents of NE, DA, and 5-HT in the hypothalamus of rats in
      the model group were significantly reduced compared with those of the normal
      group (P<0.05 or P<0.01). Compared with those in the model group, the serum
      copper content and plasma concentrations of ACTH and COR were significantly
      decreased (all P<0.05); meanwhile, serum zinc content and hypothalamic contents
      of NE, DA, and 5-HT were significantly increased in rats of the YHD group (all
      P<0.05). The same effects were also shown in the maprotiline group except for 5
      HT (all P<0.05) CONCLUSION: The pharmacological actions of YHD for depression
      might be related to improving trace-element anomalies, reversing endocrine
      dysfunction, and modulating the disorders of monoaminergic neurotransmitters.

PMID- 22415139
TI  - Therapeutic effect of Bushen Huoxue recipe on autoimmune premature ovarian
      failure mice established by immunization with recombinant porcine zona pellucida
      4 antigen.
AB  - OBJECTIVE: To investigate the efficacy and mechanism of Bushen Huoxue Recipe (,
      BHR) in the treatment of murine autoimmune premature ovarian failure (POF).
      METHODS: The recombinant porcine zona pellucida 4 (pZP4) was expressed in E. coli
      BL21 (DE3) strain within prokaryotic plasmid pET28a (+), purified by Ni-affinity
      chromatography and verified by Western blot. Murine autoimmune POF model was
      established by immunization with pZP4 of female BALB/c mice. Fifty POF mice were
      randomly divided into 5 groups, which were respectively given low (3.75 mg/kg),
      moderate (7.5 mg/kg), and high dose (15.0 mg/kg) of BHR by gastrogavage once
      daily for 20 days, with 17-beta-estradiol (0.13 mg/kg) and normal saline as
      positive and negative control. Estrous cycles were analyzed through vaginal
      smears, serum estradiol (E) levels, and anti-pZP4 antibody titers were detected
      by ELISA. The proliferative responses in vitro of spleen lymphocytes to pZP4
      antigen restimulation were measured by [(3)H]-thymidine incorporation, and the
      histomorphology changes of ovary were evaluated by optical microscope. RESULTS:
      The purified pZP4 was visible as a single lane with 14.4 kD in SDS-PAGE and
      Western blot. The murine POF model with lengthening estrous cycles, decreased
      levels of serum E2, high titers of serum anti-pZP4 antibody, and reduced ovarian
      follicles and corpus lutea were established by immunization with recombinant
      pZP4. Treatment with moderate and high dosage BHR significantly increased ovarian
      follicles and reduced the proliferation of spleen lymphocytes to the pZP4 antigen
      of POF mice (P <0.05). However, only the high dosage BHR administration
      significantly improved the estrous cycles, elevated the serum E levels (P <0.01),
      and decreased the serum anti-pZP4 antibody titers of model mice P<0.05).
      CONCLUSIONS: The recombinant pZP4 could evoke the antigen-specific immune
      response in mice and induce the autoimmune ovarian injury. It has been
      demonstrated that BHR was able to increase the serum E levels and protect ovarian
      functions from the autoimmune injury in murine POF model.

PMID- 22415140
TI  - Drug-drug interaction potential of marketed oncology drugs: in vitro assessment
      of time-dependent cytochrome P450 inhibition, reactive metabolite formation and
      drug-drug interaction prediction.
AB  - PURPOSE: To evaluate 26 marketed oncology drugs for time-dependent inhibition
      (TDI) of cytochrome P450 (CYP) enzymes. Evaluate TDI-positive drugs for potential
      to generate reactive intermediates. Assess clinical drug-drug interaction (DDI)
      risk using static mechanistic models. METHODS: Human liver microsomes and CYP
      specific probes were used to assess TDI in a dilution shift assay followed by
      generation of K(I) and k(inact). Reactive metabolite trapping studies were
      performed with stable label probes. Static mechanistic model was used to predict
      DDI risk using a 1.25-fold AUC increase as a cut-off for positive DDI. RESULTS:
      Negative TDI across CYPs was observed for 13/26 drugs; the rest were time
      dependent inhibitors of, predominantly, CYP3A. The k(inact)/K(I) ratios for 11
      kinase inhibitors ranged from 0.7 to 42.2 ml/min/MUmol. Stable label trapping
      agent-drug conjugates were observed for ten kinase inhibitors. DDI predictions
      gave no false negatives, one true negative, four false positives and three true
      positives. The magnitude of DDI was overestimated irrespective of the inhibitor
      concentration selected. CONCLUSIONS: 13/26 oncology drugs investigated showed TDI
      potential towards CYP3A, formation of reactive metabolites was also observed. An
      industry standard static mechanistic model gave no false negative predictions but
      did not capture the modest clinical DDI potential of kinase inhibitors.

PMID- 22415141
TI  - Prevalence of sleep disturbances in mild cognitive impairment and dementing
      disorders: a multicenter Italian clinical cross-sectional study on 431 patients.
AB  - BACKGROUND/AIMS: Sleep disturbances are common in the elderly and in persons with
      cognitive decline. The aim of this study was to describe frequency and
      characteristics of insomnia, excessive daytime sleepiness, sleep-disordered
      breathing, REM behavior disorder and restless legs syndrome in a large cohort of
      persons with mild cognitive impairment or dementia. METHODS: 431 consecutive
      patients were enrolled in 10 Italian neurological centers: 204 had Alzheimer's
      disease, 138 mild cognitive impairment, 43 vascular dementia, 25 frontotemporal
      dementia and 21 Lewy body dementia or Parkinson's disease dementia. Sleep
      disorders were investigated with a battery of standardized questions and
      questionnaires. RESULTS: Over 60% of persons had one or more sleep disturbances
      almost invariably associated one to another without any evident and specific
      pattern of co-occurrence. Persons with Alzheimer's disease and those with mild
      cognitive impairment had the same frequency of any sleep disorder. Sleep
      disordered breathing was more frequent in vascular dementia. REM behavior
      disorder was more represented in Lewy body or Parkinson's disease dementia.
      CONCLUSION: A careful clinical evaluation of sleep disorders should be performed
      routinely in the clinical setting of persons with cognitive decline. Instrumental
      supports should be used only in selected patients.

PMID- 22415142
TI  - Persistent and recrudescent infection in cattle following natural infection with
      Middle Point orbivirus.
AB  - Middle Point orbivirus (MPOV) is a recently described Australian arbovirus,
      related to Yunnan orbivirus from China. Analysis of genetic variation within the
      major serotype gene of MPOV isolates collected from sentinel cattle has
      identified eight co-circulating strains. The pattern of strain isolation from
      individual animals during the study period was consistent with an interpretation
      of persistent MPOV infection of up to five months, featuring episodes of
      quiescence (below levels required for virus isolation) followed by viral
      recrudescence. This is significant with regard to current interpretations of
      infection, persistence and recrudescence during natural infections of
      orbiviruses, including bluetongue virus.

PMID- 22415143
TI  - Increased risks of coronary heart disease and stroke among spousal caregivers of
      cancer patients.
AB  - BACKGROUND: Spousal caregivers of cancer patients suffer psychological and
      physical burdens that may affect their risk of subsequently developing coronary
      heart disease and stroke. METHODS AND RESULTS: Cancer patients were identified in
      the Swedish Cancer Registry, and information on their spouses was retrieved from
      the Swedish Multi-Generation Register. Follow-up of caregivers was performed from
      the date of the first diagnosis of cancer in their spouses through 2008.
      Standardized incidence ratios were calculated for spousal caregivers of cancer
      patients compared with those without an affected spouse. After the cancer
      diagnosis in wives, the risks of coronary heart disease, ischemic stroke, and
      hemorrhagic stroke in husbands were 1.13 (95% confidence interval [CI], 1.10
      1.16), 1.24 (95% CI, 1.21-1.27), and 1.25 (95% CI, 1.18-1.32), respectively. The
      corresponding risks in wives with an affected husband were 1.13 (95% CI, 1.10
      1.16), 1.29 (95% CI, 1.26-1.32), and 1.27 (95% CI, 1.19-1.34). The increases were
      consistent over time and were more pronounced if the spouse was affected by a
      cancer with a high mortality rate, such as pancreatic and lung cancers.
      CONCLUSIONS: Spousal caregivers of cancer patients have increased risks of
      coronary heart disease and stroke that persist over time. Clinical attention
      should be paid to spousal caregivers, especially those caring for cancer patients
      with high mortality rates.

PMID- 22415144
TI  - Spouses of patients with cancer have an increased risk of cardiovascular disease:
      what do we know about this link?

PMID- 22415145
TI  - Cardioprotection through S-nitros(yl)ation of macrophage migration inhibitory
      factor.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is a structurally unique
      inflammatory cytokine that controls cellular signaling in human physiology and
      disease through extra- and intracellular processes. Macrophage migration
      inhibitory factor has been shown to mediate both disease-exacerbating and
      beneficial effects, but the underlying mechanism(s) controlling these diverse
      functions are poorly understood. METHODS AND RESULTS: Here, we have identified an
      S-nitros(yl)ation modification of MIF that regulates the protective functional
      phenotype of MIF in myocardial reperfusion injury. Macrophage migration
      inhibitory factor contains 3 cysteine (Cys) residues; using recombinant wtMIF and
      site-specific MIF mutants, we have identified that Cys-81 is modified by S
      nitros(yl)ation whereas the CXXC-derived Cys residues of MIF remained unaffected.
      The selective S-nitrosothiol formation at Cys-81 led to a doubling of the
      oxidoreductase activity of MIF. Importantly, S-nitrosothiol-MIF formation was
      measured both in vitro and in vivo and led to a decrease in cardiomyocyte
      apoptosis in the reperfused heart. This decrease was paralleled by a S
      nitrosothiol-MIF- but not Cys81 serine (Ser)-MIF mutant-dependent reduction of
      infarct size in an in vivo model of myocardial ischemia/reperfusion injury.
      CONCLUSIONS: S-nitros(yl)ation of MIF is a pivotal novel regulatory mechanism,
      providing enhanced activity resulting in increased cytoprotection in myocardial
      reperfusion injury.

PMID- 22415147
TI  - Chemical characterization of acidic oligosaccharides in milk of the red kangaroo
      (Macropus rufus).
AB  - In the milk of marsupials, oligosaccharides usually predominate over lactose
      during early to mid lactation. Studies have shown that tammar wallaby milk
      contains a major series of neutral galactosyllactose oligosaccharides ranging in
      size from tri- to at least octasaccharides, as well as beta(1-6) linked N
      acetylglucosamine-containing oligosaccharides as a minor series. In this study,
      acidic oligosaccharides were purified from red kangaroo milk and characterized by
      (1)H-nuclear magnetic resonance spectrometry and matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry, to be as follows:
      Neu5Ac(alpha2-3)Gal(beta1-4)Glc (3'-SL), Neu5Ac(alpha2-3)Gal(beta1-3)Gal(beta1
      4)Glc (sialyl 3'-galactosyllactose), Neu5Ac(alpha2-3)Gal(beta1-3)Gal(beta1
      3)Gal(beta1-4)Glc, Neu5Ac(alpha2-3)Gal(beta1-3)Gal(beta1-3)Gal(beta1-3)Gal(beta1
      4)Glc, Neu5Ac(alpha2-3)Gal(beta1-3)[Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1-4)Glc
      (sialyl lacto-N-novopentaose a), Gal(beta1-3)[Neu5Ac(alpha2-6)Gal(beta1
      4)GlcNAc(beta1-6)]Gal(beta1-4)Glc (sialyl lacto-N-novopentaose b), Neu5Ac(alpha2
      3)Gal(beta1-3)Gal(beta1-3)[Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1-4)Glc, Gal(beta1
      3)(-3-O-sulfate)Gal(beta1-3)Gal(beta1-4)Glc, Gal(beta1-3)(-3-O-sulfate)Gal(beta1
      3)Gal(beta1-3)Gal(beta1-4)Glc, Gal(beta1-3)(-3-O-sulfate)Gal(beta1-3)Gal(beta1
      3)Gal(beta1-3)Gal(beta1-4)Glc, Gal(beta1-3)(-3-O-sulfate)Gal(beta1-3)[Gal(beta1
      4)GlcNAc(beta1-6)]Gal(beta1-4)Glc, Gal(beta1-3)(-3-O-sulfate)Gal(beta1
      3)Gal(beta1-3)[Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1-4)Glc. These acidic
      oligosaccharides were shown to be sialylated or sulfated in the non-reducing ends
      to the major linear and the minor branched series of neutral oligosaccharides of
      tammar wallaby milk.

PMID- 22415148
TI  - Phase I trial of irinotecan and amrubicin with granulocyte colony-stimulating
      factor support in extensive-stage small-cell lung cancer.
AB  - PURPOSE: We conducted a phase I trial of irinotecan (CPT-11), a topoisomerase I
      inhibitor, combined with amrubicin, a topoisomerase II inhibitor, with
      recombinant human granulocyte colony-stimulating factor (rhG-CSF) support to
      overcome the neutropenia associated with this particular combination. The aim was
      to determine the maximum tolerated dose (MTD) of amrubicin combined with a fixed
      dose of CPT-11 and the dose-limiting toxicities (DLTs) of this combination in
      extensive-stage small-cell lung cancer (ED-SCLC) patients. METHODS: Fifteen
      patients with ED-SCLC were treated at 3-week intervals with amrubicin on days 1-3
      plus 60 mg/m(2) CPT-11 on days 1 and 8. In addition, prophylactic rhG-CSF (50
      MUg/m(2)) was given from day 4 to day 21, except on the day of CPT-11
      administration. Amrubicin was started at 30 mg/m(2) and then escalated in 5
      mg/m(2) increments until MTD was reached. RESULTS: The MTD of amrubicin was 35
      mg/m(2), since 2 of 4 patients experienced DLTs during the first cycle of
      treatment at the 40 mg/m(2) dose level. Neutropenia, neutropenic fever, ileus,
      and diarrhea were the DLTs. There were 13 partial responses among the 13
      assessable patients, yielding an overall response rate of 100 %. Median
      progression-free survival and overall survival were 7.4 months and 13.4 months,
      respectively. CONCLUSION: The combination of amrubicin and CPT-11 showed high
      activity against ED-SCLC with acceptable toxicity. Use of rhG-CSF allowed the
      dose of amrubicin to be raised 40 % above that in the original regimen (60
      mg/m(2) CPT-11 and 25 mg/m(2) amrubicin).

PMID- 22415149
TI  - Prediction of ADHD to anxiety disorders: an 11-year national insurance data
      analysis in Taiwan.
AB  - OBJECTIVE: To prospectively investigate prediction of ADHD to anxiety disorders
      (ANXs) in a national sample of Taiwan. METHOD: From the Taiwan National Health
      Insurance Dataset (1997-2007), we collected 2,385 cases of new diagnoses of ADHD
      from 1999 to 2003 and 9,540 sex-, age- and index dates of the first diagnosis of
      ADHD-matched cohort controls without ADHD. The outcome is age of the first
      diagnosis of ANXs until December 31, 2007. RESULTS: More cases of ADHD (17.7%)
      developed ANXs than did matched controls (1.9%) with a younger age onset (12.7
      years vs. 17.9 years) and a shorter "survival time" (1.4 years vs. 5.0 years).
      Cox models revealed a significant prediction of ADHD to ANXs controlling for
      other psychiatric comorbidities [Hazard ratio (HR) = 15.83]. The magnitude of
      such association was greater in males and decreased with older age of first ADHD
      diagnosis. CONCLUSION: The findings imply that early detection and treatment for
      ADHD may offset later development of ANXs.

PMID- 22415150
TI  - Elevated tear interleukin-6 and interleukin-8 levels associated with silicone
      hydrogel and conventional hydrogel contact lens wear.
AB  - PURPOSE: The aim of this study was to evaluate the ocular tear interleukin (IL)-6
      and IL-8 concentrations within the first 6 months of contact lens (CL) wear in
      eyes of neophyte CL users who had been commenced on either silicone hydrogel CL
      (SH-CL) or conventional hydrogel CL (CH-CL). METHODS: Twenty-four subjects with
      no history of CL wear received either SH-CL (n=12) or CH-CL (n=12) for a period
      of 6 months in this prospective study. Tear IL-6 and IL-8 concentrations were
      determined before CL wear (0 months) and at 1, 3, and 6 months after CL
      commencement. The sera of all the subjects were tested and graded (grades 0-6)
      for grass, weed, and tree pollen-specific immunoglobulin E (IgE) levels. RESULTS:
      Tear IL-6 concentrations at 0, 1, 3, and 6 months for SH-CL and CH-CL users were
      7.1 +/- 6.4, 10.5 +/- 8.9, 18.6 +/- 17.0, 33.1 +/- 15.0 pg/mL and 10.9 +/- 8.2,
      6.4 +/- 4.0, 24.2 +/- 13.2, 34.4 +/- 17.5 pg/mL, respectively. In both groups, IL
      6 levels were significantly elevated at 6 months compared with those at 0 months
      (P<0.001). Tear IL-8 concentrations at 0, 1, 3, and 6 months for SH-CL and CH-CL
      users were 107.4 +/- 56.8, 106.0 +/- 47.4, 319.5 +/- 154.8, 412.6 +/- 104.1 pg/mL
      and 176.4 +/- 59.7, 196.2 +/- 145.0, 410.7 +/- 121.2, 456.7 +/- 19.2 pg/mL,
      respectively. In both groups, tear IL-8 levels were significantly elevated at 6
      months compared with those at 0 months (P<0.001). The tear IL-6 and IL-8 levels
      were found to be similar within the 2 groups at the 6-month time point (P>0.05).
      The serum grass, weed, and tree pollen-specific IgE levels were similar between
      groups (P>0.05) and less than 0.35 kU/L (grade 0) in 22 of 24 (91.7%)
      participants tested. CONCLUSIONS: The SH-CL and CH-CL wear is associated with
      elevation of IL-6 and IL-8 levels in the tears of healthy, nonatopic neophyte CL
      users.

PMID- 22415151
TI  - Automatic segmentation of the central epithelium imaged with three optical
      coherence tomography devices.
AB  - PURPOSE: The aim of this study was to investigate the feasibility of automatic
      segmentation of the central corneal thickness (CCT) and epithelial thickness (ET)
      of the human cornea obtained with different spectral domain optical coherence
      tomography (OCT) instruments. METHODS: Ten left eyes from 10 healthy subjects
      with a mean age of 22.5 +/- 1.5 years participated in this study. A custom-built
      ultra-high resolution OCT (UHR-OCT) with a 3-MUm axial resolution, ultralong scan
      depth OCT (UL-OCT) with a 7.5-MUm resolution, and commercial RTVue OCT with a 5
      MUm resolution were used to image the cornea. An automated segmentation algorithm
      was developed to process the OCT images and yield the CCT and ET. The measurement
      was verified by a manual measurement. RESULTS: The automatic algorithm
      successfully processed the central thickness of the cornea and corneal epithelium
      for all images. The average CCT obtained by the automatic segmentation algorithm
      was 528.1 +/- 22.4 MUm, 526.1 +/- 23.4 MUm, and 525.2 +/- 23.7 MUm for UHR-OCT,
      UL-OCT, and RTVue, respectively. The average ET was 53.2 +/- 2.0 MUm, 54.1 +/-
      3.0 MUm, and 52.1 +/- 2.5 MUm for UHR-OCT, UL-OCT, and RTVue, respectively. These
      measurements were in agreement with those of the manual method for the CCT (all
      r>0.997, P<0.05) and for the ET (all r>0.71, P<0.05). CONCLUSIONS: The algorithm
      seemed to be feasible for automatically segmenting the CCT and ET in OCT images
      using these tested OCT devices. The segmented results were equivalent to that
      obtained with the manual method.

PMID- 22415152
TI  - Accuracy and repeatability of a new tono-pachymeter for measuring central corneal
      thickness.
AB  - OBJECTIVES: The recently developed noncontact tonopachymeter Tonopachy NT-530 P
      provides intraocular pressure values corrected for central corneal thickness
      (CCT). The purpose of this study was to assess the accuracy and repeatability of
      its CCT measurements. METHODS: The CCT measurements were obtained in 64 right
      eyes of 64 young healthy subjects using the Orbscan corneal topography system
      followed by the Tonopachy and then by ultrasound pachymetry (UP). Another sample
      of 31 subjects was used to test the repeatability of the tonopachy measurements
      in 2 separate sessions 1 week apart. To compare the tonometers and determine
      intersession repeatability for the tonopachymeter, differences in the readings
      provided by pairs of the instruments or obtained in the two sessions were plotted
      against mean differences. The hypothesis of zero bias was examined by a paired t
      test. The coefficient of repeatability was calculated as the 95% limits of
      agreement (LoAs) of differences between the 2 sessions. RESULTS: Measurements
      made using the three instruments were significantly correlated (P<0.001). Mean
      CCTs (+/-SD) measured using the Tonopachy, Orbscan (acoustic factor set at 0.92)
      and ultrasound pachymeter were 530.42 +/- 34.96, 526.73 +/- 39.53, and 550.69 +/-
      37.26 MUm, respectively. The differences between modalities (+/-95% LoAs) were 
      3.68 +/- 24.36 for Orbscan versus Tonopachy, 20.66 +/- 14.69 for UP versus
      Tonopachy, and 23.95 +/- 24.21 for UP versus Orbscan. The coefficient of
      repeatability for the tonopachymeter was +/-15.11 MUm. CONCLUSIONS: The Tonopachy
      offers similar CCT measurements to those provided by conventional pachymeters
      with good repeatability.

PMID- 22415153
TI  - Case report: a successful LipiFlow treatment of a single case of meibomian gland
      dysfunction and dropout.
AB  - OBJECTIVE: The aim of this study was to investigate whether a single case of
      meibomian gland dysfunction (MGD), with significant MG dropout resulting in
      evaporative dry eye, could be effectively treated with the LipiFlow (a new Food
      and Drug Administration-approved thermodynamic pulsatile treatment). MATERIALS
      AND METHODS: A 39-year-old white woman experienced severe dry eye symptoms
      because of MGD with considerable MG dropout resulting in evaporative dry eye.
      Standardized diagnostic MG expression and meibography led to the tentative
      diagnosis of nonobvious MGD (only 1 functional MG on each lower lid) and MG
      dropout (~50% of the lower lid MGs were missing with the remaining MGs being
      severely truncated). The patient underwent a single 12-min LipiFlow treatment per
      eye and returned for follow-up at 1 and 7 months posttreatment. RESULTS: The
      LipiFlow treatment increased the number of functional lower lid MGs from 1 to 5
      glands OD and 1 to 7 glands OS at 1 month with slight regression at 7 months (4
      OD and 4 OS); increased fluorescein break-up time from 4 to 7 sec OD and 4 to 9
      sec OS at both 1 and 7 months; and decreased symptom scores by approximately 50%
      at 1 month and approximately 75% at 7 months. CONCLUSIONS: These results
      demonstrate the effectiveness of the LipiFlow in restoring MG function and
      improving ocular comfort even in this particular case of significant MG dropout
      and MG truncation.

PMID- 22415154
TI  - Analysis of sentinel lymph node biopsy results in colon cancer in regard of the
      anthropometric features of the population and body composition assessment
      formulas.
AB  - PURPOSE: The aim of the study was to assess sentinel lymph node biopsy (SLNB)
      results in colon cancer (CC) regarding basic anthropometric features of the
      studied population and their derivatives calculated using mathematical formulas.
      METHODS: One hundred three SLNBs in CC have been analysed. Various indicators
      were calculated for every patient using mathematical formulas: BMI, Roher's
      index, lean body weight, body fat percentage and body weight/ideal body weight
      for a given height ratios using the following formulas: Broca's, Broca's ideal
      weight, Broca-Brugsch, Lorenz's, Potton's, Devine's, Robinson's, Miller's and
      Hamwi. The results were compared with accuracy, sensitivity and false negative
      results percentage by means of ROC curves and the test for structure indicators
      (for determined cut-off points). RESULTS: No statistically significant
      relationship between the results and patients' sex or age were found. ROC curve
      analysis did not reveal statistically significant relationships between the
      obtained results and indicators calculated on the basis of growth and weigh (all
      p > 0.05). The analyses of sensitivity and accuracy with determined cut-off
      point, in spite of differences amounting to 19 % (analysis of lean body
      weight/weight ratio), showed no statistical significance for any of the
      relationships (all p > 0.05). CONCLUSIONS: No indicator with high diagnostic and
      prognostic value has been found. The problem of qualifying patients for SLNB in
      CC in regard of the anthropometric features of the population and body
      composition assessment formulas remains open and requires further analysis on
      larger populations.

PMID- 22415156
TI  - MSNA during prolonged post-faint hypotension.
AB  - BACKGROUND: Following tilt-induced syncope, blood pressure usually recovers
      rapidly after tilt back to the horizontal position. However, in some patients,
      hemodynamic recovery is delayed, a condition recently termed "prolonged post
      faint hypotension" (PPFH). The mechanism is thought to be mediated by increased
      vagal outflow rather than exaggerated peripheral vasodilatation and sympathetic
      withdrawal. To date, no muscle sympathetic nerve activity (MSNA) recordings have
      been reported in this condition, so we aimed to confirm that neither
      vasodilatation nor MSNA withdrawal was responsible. OBJECTIVES: To
      retrospectively select patients with satisfactory recordings of continuous BP and
      MSNA during tilt-induced syncope. To compare hemodynamic and MSNA profiles in
      patients with PPFH to patients with normal recovery (NR) after tilt-back.
      METHODS: All patients were studied in Christchurch, New Zealand, between 1998 and
      2008 using continuous arterial BP monitoring, and microneurographic recordings of
      MSNA from the right leg. Only patients with satisfactory BP and MSNA data
      throughout baseline, head-up tilt and presyncope were selected. Stroke volume
      (SV), cardiac output (CO), and total peripheral resistance (TPR) were derived
      using Modelflow. After baseline measurements, patients were tilted to the head-up
      60 degrees  position and given GTN spray if asymptomatic after 20 min. Following
      the onset of presyncope, patients were tilted slowly back to the horizontal. PPFH
      was defined as systolic BP <85 mmHg for at least 2 min after tilt-back.
      Measurements were averaged at baseline, early tilt, presyncope, early and late
      recovery. Within-group comparisons were made between baseline and all other time
      points. Between-group comparisons were made over all time points. RESULTS:
      Patients with PPFH (7 males, age 46 +/- 5 years, n = 8) and with NR (8 males, age
      47 +/- 6 years, n = 8) were selected. Presyncope was provoked by GTN in 4/8
      patients in each group. In both groups, MAP remained below baseline during early
      and late recovery: PPFH 84 +/- 5 versus 51 +/- 5 and 64 +/- 5 mmHg (p = 0.001, p
      = 0.001); NR 104 +/- 5 versus 83 +/- 5 and 93 +/- 5 mmHg (p = 0.001, p = 0.03).
      However, MAP and HR were lower in the PPFH group (p = 0.004, p = 0.023). During
      early recovery, CO remained below baseline only in the PPFH group (p = 0.001),
      whereas TPR remained constant in both groups. In both groups, all MSNA indices
      tended to remain above baseline levels during early and late recovery. PPFH 25 +/
      2 increased to 31 +/- 6 and 29 +/- 4 bursts/min (p = 0.09, 0.02); NR 23 +/- 3
      increased to 33 +/- 3 and 34 +/- 3 bursts/min (p = 0.06, 0.01). CONCLUSIONS: PPFH
      does not appear to be mediated by exaggerated vasodilatation or sympathetic
      withdrawal. Delayed recovery of cardiac output by increased vagal outflow is a
      more likely mechanism.

PMID- 22415155
TI  - Targeting the vasculature of visceral tumors: novel insights and treatment
      perspectives.
AB  - BACKGROUND: Angiogenesis, the formation of new blood vessels from the endothelium
      of the existing vasculature, describes a crucial process in tumor growth, disease
      progression, and metastasis. Therefore, the upcoming strategy of inhibiting tumor
      angiogenesis has generated different treatment modalities, which have been
      transferred into clinical practice in recent years. Currently, this concept is
      applied to target the vasculature of different visceral tumors and intensive
      clinical research has just started. MATERIALS AND METHODS: This review summarizes
      the modifications of systemic treatment of visceral tumors by targeting the
      vasculature in the past years. Moreover, novel targets and treatment strategies
      will be discussed to evaluate future directions. RESULTS: Leading antiangiogenic
      drugs combined with systemic chemotherapy have been applied with increasing
      success during the last years. Therefore, the concept of combining vascular
      targeting agents with established chemotherapeutic regimens has been increasingly
      adopted into the therapies of different visceral tumors. CONCLUSION: Targeting
      the vasculature of visceral tumors in combination with established standard tumor
      therapies includes major clinical potential for future therapy concepts.

PMID- 22415157
TI  - A novel synthetic strategy for monosubstituted cyclodextrin derivatives.
AB  - A first solid phase approach to obtain monosubstituted CD conjugates to different
      labels has been developed. A new solid support has been designed to get a variety
      of C-6 monofunctionalized CDs (alpha, beta, MebetaCD and HPbetaCD) covalently
      linked through a phosphodiester bridge to different labels, in highly pure form
      and under very mild detachment conditions.

PMID- 22415158
TI  - Vibrations and hydrogen bonding in porphycene.
AB  - Combined use of IR, Raman, neutron scattering and fluorescence measurements for
      porphycene isolated in helium nanodroplets, supersonic jet and cryogenic
      matrices, as well as for solid and liquid solutions, resulted in the assignments
      of almost all of 108 fundamental vibrations. The puzzling feature of porphycene
      is the apparent lack of the N-H stretching band in the IR spectrum, predicted to
      be the strongest of all bands by standard harmonic calculations. Theoretical
      modeling of the IR spectra, based on ab initio molecular dynamics simulations,
      reveals that the N-H stretching mode should appear as an extremely broad band in
      the 2250-3000 cm(-1) region. Coupling of the N-H stretching vibration to other
      modes is discussed in the context of multidimensional character of intramolecular
      double hydrogen transfer in porphycene. The analysis can be generalized to other
      strongly hydrogen-bonded systems.

PMID- 22415159
TI  - Endogenous opioid and cannabinoid mechanisms are involved in the analgesic
      effects of celecoxib in the central nervous system.
AB  - BACKGROUND/AIMS: In this study we analyzed the mechanisms underlying celecoxib
      induced analgesia in a model of inflammatory pain in rats, using the
      intracerebroventricular (i.c.v.) administration of selective opioid and
      cannabinoid antagonists. METHODS AND RESULTS: Analgesic effects of celecoxib were
      prevented by selective MU-(beta-funaltrexamine) and delta-(naltrindole), but not
      kappa-(nor-binaltorphimine) opioid antagonists, given i.c.v. 30 min before
      celecoxib. Similar pretreatment with AM 251, but not SR 144528, cannabinoid CB(1)
      and CB(2) receptor antagonists, respectively, prevented celecoxib-induced
      analgesia. The fatty acid amide hydrolase inhibitor, URB 597, also prevented
      celecoxib-induced analgesia. CONCLUSIONS: Our data provided further evidence for
      the involvement of endogenous opioids and revealed a new cannabinoid component of
      the mechanism(s) underlying celecoxib-induced analgesia.

PMID- 22415160
TI  - Public health genomics in Spain: the status of a non-existing reality.
AB  - AIMS: The Public Health Genomics European Network (PHGEN) aimed, among other
      objectives, to identify the geographical variability and legal barriers of
      genomic medicine and public health genomics (PHG) at an international market,
      where the lack of policy coherence may limit its development in Europe. PHGEN
      supported the creation of National Task Forces (NTF) to overview the national
      settings and identify proposals in different European countries. Here we
      summarize the key issues which emerged during the discussions conducted within
      the Spanish NTF. METHODS: The Spanish NTF is composed of 25 experts and key
      leaders in PHG-related areas of knowledge and met 3 times between January 2007
      and 2008 to identify, discuss and propose recommendations for the development and
      use of PHG in Spain. Discussions were recorded and shared with participants for
      amendments. RESULTS: We observed lack of applied knowledge on PHG, training
      skills and capacities on genomics of the involved specialists (gynecology,
      pediatrics, oncology, etc.), lack of applied research on diagnostics and
      knowledge on the topic in the population and mass media. Some promoting factors
      were observed, such as plans on genetics in the different regional autonomous
      communities, guidance on the introduction of genomic technologies and the new
      regional health technology regulatory frameworks. CONCLUSION: Although there is a
      current Spanish regulatory framework for the introduction of health technologies
      and a published biomedical law that could be useful for the development of PHG in
      Spain, specific and tailored initiatives should be promoted by regional and
      national authorities to improve the accreditation professionals and to inform the
      citizens on genomic technologies in order to empower them.

PMID- 22415162
TI  - Bird-nest puzzle: can the study of unisexual flowers such as cucumber solve the
      problem of plant sex determination?
AB  - Unisexual flower development has long been used as a model system to understand
      the mechanism of plant sex determination. However, based on our investigation of
      the mechanisms regulating the development of unisexual cucumber flowers, we have
      realized that understanding how organ development is inhibited may not
      necessarily reveal how an organ is formed. We refer to this problem as a "bird
      nest puzzle," meaning one cannot understand how a bird lays and hatches its eggs
      by understanding how its nest is ruined. To understand the biological
      significance of unisexual flowers, we reexamine the original meaning of sex and
      its application in plants. Additionally, we propose that the fundamental
      biological advantage for the selection and maintenance of unisexual flowers
      during evolution is to promote cross pollination.

PMID- 22415163
TI  - CTCF-binding sites within the H19 ICR differentially regulate local chromatin
      structures and cis-acting functions.
AB  - It is generally assumed that CTCF-binding sites are synonymous with the
      demarcation of expression domains by promoting the formation of chromatin loops.
      We have proposed earlier, however, that such features may be context-dependent.
      In support of this notion, we show here that chromatin loop structures, impinging
      on CTCF-binding sites 1/2 and 3/4 at the 5' and 3'-ends, respectively, within the
      maternal allele of the H19 imprinting control region (ICR), differ significantly.
      Although abrogation of CTCF binding to the maternal H19 ICR allele results in
      loss of chromatin loops in the 3'-region, there is a dramatic gain of long-range
      chromatin loops impinging on the 5'-region. As the degree of occupancy of its
      four CTCF-binding sites discriminates between the chromatin insulator and
      replication timing functions, we submit that the CTCF-binding sites within the
      H19 ICR are functionally diverse and organize context-dependent higher order
      chromatin conformations.

PMID- 22415161
TI  - Expression of wheat Na(+)/H(+) antiporter TNHXS1 and H(+)- pyrophosphatase TVP1
      genes in tobacco from a bicistronic transcriptional unit improves salt tolerance.
AB  - Abiotic stress tolerance of plants is a very complex trait and involves multiple
      physiological and biochemical processes. Thus, the improvement of plant stress
      tolerance should involve pyramiding of multiple genes. In the present study, we
      report the construction and application of a bicistronic system, involving the
      internal ribosome entry site (IRES) sequence from the 5'UTR of the heat-shock
      protein of tobacco gene NtHSF-1, to the improvement of salt tolerance in
      transgenic tobacco plants. Two genes from wheat encoding two important vacuolar
      ion transporters, Na(+)/H(+) antiporter (TNHXS1) and H(+)-pyrophosphatase (TVP1),
      were linked via IRES to generate the bicistronic construct TNHXS1-IRES-TVP1.
      Molecular analysis of transgenic tobacco plants revealed the correct integration
      of the TNHXS1-IRES-TVP1construct into tobacco genome and the production of the
      full-length bicistronic mRNA from the 35S promoter. Ion transport analyses with
      tonoplast vesicles isolated from transgenic lines confirmed that single
      transgenic lines TVP1cl19 and TNHXS1cl7 had greater H(+)-PPiase and Na(+)/H(+)
      antiport activity, respectively, than the WT. Interestingly, the co-expression of
      TVP1 and TNHXS1 increased both Na(+)/H(+) antiport and H(+)-PPiase activities and
      induced the H(+) pumping activity of the endogenous V-ATPase. Transgenic tobacco
      plants expressing TNHXS1-IRES-TVP1 showed a better performance than either of the
      single gene-transformed lines and the wild type plants when subjected to salt
      treatment. In addition, the TNHXS1-IRES-TVP1 transgenic plants accumulated less
      Na(+) and more K(+) in their leaf tissue than did the wild type and the single
      gene-transformed lines. These results demonstrate that IRES system, described
      herein, can co-ordinate the expression of two important abiotic stress-tolerance
      genes and that this expression system is a valuable tool for obtaining transgenic
      plants with improved salt tolerance.

PMID- 22415165
TI  - Essential resources from the WOCN Society: a special supplement to the Journal of
      Wound, Ostomy and Continence Nursing.

PMID- 22415164
TI  - Retrotransposons as a major source of epigenetic variations in the mammalian
      genome.
AB  - Transcription of retrotransposons is usually repressed by DNA methylation, but a
      few elements, such as intracisternal A-particles (IAPs) associated with the
      Agouti and Axin-fused loci, partially escape this repression mechanism. The
      levels of this repression are also variable among individuals with an identical
      genome sequence, generating epigenetically different states of loci or
      'epialleles.' In the current study, we tested the existence of additional
      retrotransposon-derived epialleles in the mouse genome. Using a series of
      bioinformatic approaches, 143 candidate epialleles were first identified from the
      mouse genome based on their promoter activity and association with active histone
      modification marks. Detailed analyses suggest that a subset of these elements
      showed variable levels of DNA methylation among the individual mice of an
      isogenic background, revealing their stochastic nature (metastability) of DNA
      methylation. The analyses also identified two opposite patterns of DNA
      methylation during development, progressive gaining vs. losing, confirming the
      dynamic nature of their DNA methylation patterns. qRT-PCR analyses demonstrated
      that the expression levels of these elements are indeed variable among the
      individual mice, suggesting functional consequences on their associated
      endogenous genes. Overall, these data confirm the presence of a number of new
      retrotransposon-derived epialleles with suggestions of the presence of more, and
      further identify retrotransposons as a major source of epigenetic variations in
      the mammalian genome.

PMID- 22415166
TI  - Understanding Medicare Part B Incident to Billing: a fact sheet.

PMID- 22415167
TI  - Position statement about the role and scope of practice for wound care providers.

PMID- 22415168
TI  - Ankle Brachial Index: quick reference guide for clinicians.

PMID- 22415169
TI  - Clean vs. sterile dressing techniques for management of chronic wounds: a fact
      sheet.

PMID- 22415170
TI  - Introduction to Reimbursement of Advanced Practice Registered Nurse Services and
      Understanding Medicare Part B Incident to Billing.

PMID- 22415171
TI  - Reimbursement of Advanced Practice Registered Nurse Services: a fact sheet.

PMID- 22415172
TI  - Probing the role of encapsulated alkaline earth metal atoms in endohedral
      metallofullerenes M@C76 (M = Ca, Sr, and Ba) by first-principles calculations.
AB  - By means of density functional theory and statistical mechanics, we investigate
      the geometric and electronic structures, thermodynamic stability and infrared
      (IR) vibrational frequencies of alkaline earth metal endohedral fullerenes,
      M@C(76) (M = Ca, Sr, and Ba). The results reveal that M@C(1)(17,459)-C(76)
      possesses the lowest energy followed by M@C(2v)(19,138)-C(76) with a very small
      energy difference. Both the structures have a pair of adjacent pentagons and are
      related by a single Stone-Wales transformation. Equilibrium statistical
      thermodynamic analyses based on Gibbs energy treatments suggest that
      M@C(1)(17,459)-C(76) has a prominent thermodynamic stability at higher
      temperatures, in contrast with M@C(2v)(19,138)-C(76) whose thermodynamic
      stability is affected by the encapsulated metal atom. The encapsulated metallic
      atoms as well as cage structures significantly influence the electronic
      properties of endohedral fullerenes such as electron affinities and ionization
      potentials. On the other hand, the singlet-triplet splitting energy DeltaE(S-T)
      depends on the cage structures. In addition, IR spectra and chemical shifts of
      these compounds have been computed to assist further experimental
      characterization.

PMID- 22415173
TI  - Mental health of the elderly in Brazil: the relevance of epidemiological
      research.

PMID- 22415174
TI  - [Survival analysis of dialysis patients in the Brazilian Unified National Health
      System].
AB  - The aim of this study was to analyze the survival of patients who initiated renal
      replacement therapy (RRT) with hemodialysis or peritoneal dialysis in the
      Brazilian Unified National Health System from 2002 to 2004. This was an
      observational, prospective, non-concurrent study. The study used the National
      Database for Renal Replacement Therapies resulting from probabilistic matching of
      Authorization of High-Complexity Procedures/Outpatient Information System and the
      Mortality Information System. The study included patients admitted in 2002 and
      2003, with 3 months of treatment, and 18 years or older. Of the 31,298 patients,
      the majority: began RRT with hemodialysis, were male, with mean age 54 years, and
      living in the Southeast region and in municipalities with a mean HDI of 0.78.
      Increased risk of death was associated with: female gender, age greater than 55
      years, diagnosis of diabetes mellitus, peritoneal dialysis, and not residing in
      the Southeast region. Residing in cities with higher HDI was associated with
      lower risk. Adjusted risk was HR = 1.17 in favor of hemodialysis. The results
      suggest shorter survival for peritoneal dialysis and older patients. It is thus
      necessary to support policies to better evaluate the RRT modality with studies
      that further elucidate the findings.

PMID- 22415175
TI  - [Adequacy of prenatal care in the National Health System in the city of Rio de
      Janeiro, Brazil].
AB  - The persistence of negative perinatal outcomes in Rio de Janeiro suggests
      problems in the quality of prenatal care. The most recent study in the city
      showed that only 38% of prenatal care was adequate. This study aimed to evaluate
      the adequacy of prenatal care under the Brazilian Unified National Health System
      in the city of Rio de Janeiro. A cross-sectional study in 2007-2008 interviewed
      2,422 women receiving prenatal care for low-risk pregnancy. Evaluation of care
      used the PHPN index, based on guidelines from the Program for Humanization of
      Prenatal Care and Childbirth (Brazilian Ministry of Health) and an expanded PHPN
      index, which included clinical-obstetric procedures, prescription of
      supplementary ferrous sulfate, and educational activities. According to the PHPN
      index, 38.5% of prenatal care was adequate, as compared to 33.3% based on the
      expanded PHPN index. Strategies to expand early entry of pregnant women into
      prenatal care and better use of their contact with the health services in order
      to promote healthcare measures are essential to correct this situation.

PMID- 22415176
TI  - [Distribution of general and abdominal obesity in adults in a city in southern
      Brazil].
AB  - The objective of this study was to determine the prevalence and trends in general
      and abdominal obesity in adults 20 years or older in Pelotas, Rio Grande do Sul
      State, Brazil, using a cross-sectional population-based design, in 2010. General
      obesity was defined as body mass index (BMI) > 30 kg/m2 and abdominal obesity as
      waist circumference (WC) > 88 cm for women and > 102 cm for men. Interviews were
      held with 2,448 eligible individuals. General obesity prevalence was 21.7% in men
      and 29.2% in women, while abdominal obesity was present in 19.5% of men and 37.5%
      of women. According to multivariate analysis, lower schooling was associated with
      increased BMI and WC in women. Family income was inversely related to abdominal
      obesity in men. Prevalence of general obesity had increased 1.2 times in women
      and 1.5 in men, when compared to studies in 1994 and 2000. Abdominal obesity
      showed a small decrease in women, but remained stable in men. Prevalence of
      general obesity increased in the previous 10 years, while abdominal obesity
      remained basically stable.

PMID- 22415177
TI  - [Impact of the Family Health Strategy: an analysis in cities in Northeast Brazil
      with more than 100,000 inhabitants].
AB  - This study aimed to analyze the impact of the Family Health Strategy (FHS) on
      oral health in Northeast Brazil, in 12 municipalities with more than 100 thousand
      inhabitants. The reference was 20 census tracts, 10 of which in areas with oral
      health covered by the FHS for at least a year, matched with 10 census tracts
      without oral health coverage. The total sample included 59,221 individuals. Three
      possible effects were considered: negative, positive, and absence of effect on
      the outcomes, based on the prevalence ratio adjusted by Poisson regression. The
      outcomes "access to collective preventive measures" and "treatment of toothache"
      indicate a positive effect in the FHS oral health model. However, the outcomes
      "coverage of tooth extraction" and "restorative treatment" showed either a
      negative effect or no effect in the majority of the municipalities in the sample.
      Evidence indicates that within the FHS, the results reflect the local
      organizational models for oral health care.

PMID- 22415178
TI  - Association between levels of physical activity and use of medication among older
      women.
AB  - The aim of this study was to determine the association between levels of physical
      activity and usage of medication in older women. The level of physical activity
      was assessed using a pedometer. Use of medication was assessed through medical
      records supplied in reports kept by the Family Health Program, City Health
      Department, Sao Caetano do Sul, Sao Paulo State, Brazil. Regular use of
      pharmaceuticals, regardless of type of illness or treatment, was listed. Data
      analysis was performed using Poisson regression to estimate the prevalence ratio.
      The results of the study indicated that, amongst the 271 eligible women, 84.9%
      had been classified as active. Only 23.2% did not use any type of medication
      while 29.8% used three or more medications. The level of physical activity was
      inversely associated with the number of medications used, under both crude
      analysis and after adjustment. The study concluded that higher volumes of
      physical activity were significantly associated with lower usage of
      pharmaceuticals in women who are involved in a physical activity program.

PMID- 22415179
TI  - [Hepatitis B mortality in Brazil, 2000-2009].
AB  - This descriptive study focused on the mortality profile associated with hepatitis
      B virus (HBV) in Brazil as a whole and by region, based on data from the
      Mortality Information System (MIS). The study sample consisted of deaths from HBV
      recorded in the MIS from January 1, 2000, to December 31, 2009. The crude
      mortality rate remained constant in the country; the proportion of hepatocellular
      carcinoma with HBV as the associated cause was no greater than 7%. The
      standardized mortality rate was highest in the North of Brazil, and the
      proportional mortality rate was higher in males. In 2009, the potential years of
      life lost (PYLL) were highest in males in the 50-59-year age bracket and in
      females in the 40-49-year bracket. The largest increase in PYLL occurred in males
      60 to 69 years of age. The study emphasizes the importance of scaling up
      preventive measures against HBV, in addition to expanding access to early
      diagnosis in order to reduce HBV mortality in the coming decades.

PMID- 22415180
TI  - [Consequences of the judicialization of health policies: the cost of medicines
      for mucopolysaccharidosis].
AB  - This study analyzes expenditures backed by court rulings to ensure the public
      provision of medicines for treatment of mucopolysaccharidosis (MPS), a rare
      disease that requires high-cost drugs not covered by the Brazilian government's
      policy for pharmaceutical care and which have disputed clinical efficacy. The
      methodology included a review of files from 196 court rulings ordering the
      Brazilian Ministry of Health to provide the medicines, in addition to Ministry of
      Health administrative records. According to the analysis, the "judicialization"
      of the health system subjected the Brazilian government to a monopoly in the
      distribution of medicines and consequently the loss of its capacity to manage
      drug purchases. The study also indicates that the imposition of immediate,
      individualized purchases prevents obtaining economies of scale with planned
      procurement of larger amounts of the medication, besides causing logistic
      difficulties in controlling the amounts consumed and stored. In conclusion,
      litigation results from the lack of a clear policy in the health system for rare
      diseases in general, thereby leading to excessive expenditures for MPS treatment.

PMID- 22415181
TI  - [Coverage by the Family Health Strategy and diagnosis of syphilis in pregnancy
      and congenital syphilis].
AB  - This paper aimed to correlate syphilis in pregnancy and congenital syphilis with
      coverage of the Family Health Strategy (FHS), based on available data in the
      national health information systems. The syphilis notification estimates were
      calculated according to the Sentinel Childbirth Study for 2004 under the Ministry
      of Health and the data were obtained from the websites of the Health Surveillance
      Secretariat and Healthcare Secretariat, for the year 2008. The ratios between
      observed and estimated gestational syphilis and congenital syphilis were not
      statistically correlated with population coverage by the FHS (r = -0.28 and r = 
      0.40, respectively). The FHS is a privileged area for prenatal care and logically
      a source of compulsory notification of syphilis in pregnancy. By combining
      diagnosis with adequate treatment of syphilis in pregnant women and their
      partners, the FHS becomes a prime instrument for eliminating congenital syphilis
      in Brazil. Expanding the FHS coverage and quality of care are essential for
      achieving this goal.

PMID- 22415182
TI  - Epidemiological changes and financial consequences of hypertension in Latin
      America: implications for the health system and patients in Mexico.
AB  - The aim of this study was to assess the costs and financial consequences of
      epidemiological changes in hypertension in Mexico. The cost evaluation method to
      estimate costs was based on instrumentation techniques. To estimate the
      epidemiological changes and expected cases of hypertension in 2010-2012, three
      probabilistic models were constructed according to the Box-Jenkins technique.
      Comparing the economic impact, from 2010 to 2012 there will be a 24% increase in
      financial requirements (p < 0.05). The total cost of hypertension in 2011 will be
      US$ 5,733,350,291, including US$ 2,718,280,941 in direct costs and US$
      3,015,069,350 in indirect costs. If the risk factors and various healthcare
      models remain unaltered in the institutions analyzed here, the financial
      consequences will have a major impact on users' pockets, followed by social
      security providers and public healthcare providers. The authors suggest a
      revision in the planning, organization, and allocation of resources, particularly
      programs for health promotion and prevention of hypertension.

PMID- 22415184
TI  - [The Family Health Strategy and hospital admissions of children under five years
      in Piaui State, Brazil].
AB  - Hospitalizations for some health conditions can be reduced by timely primary care
      with appropriate quality, especially in children. This study analyzed the trend
      in hospitalizations in children under five years of age in Piaui State, Brazil,
      from 2000 to 2010, according to groups of causes (ICD-10) and hospital admissions
      in 2010, based on the Brazilian List of Hospitalizations for Primary Care
      Sensitive Conditions. The objectives were to identify changes in the hospital
      morbidity profile and to discuss their relationship to expansion of the Family
      Health Strategy (FHS) in the State. Piaui showed the highest proportional
      expansion of the FHS in Brazil, reaching an estimated coverage of 97.2% in 2010.
      From 2000 to 2010, there was a reduction in the hospitalization frequency and
      rates in children under five years, but the proportion of hospitalizations in the
      leading groups of causes persisted or increased during the decade. In 2010, 60%
      of hospitalizations in children under five years were for causes that are
      sensitive to primary care, especially infectious gastroenteritis, respiratory
      infections, and asthma.

PMID- 22415183
TI  - [Prevalence of minor psychiatric disorders among primary healthcare workers in
      the South and Northeast regions of Brazil].
AB  - Mental health problems are among the most prevalent conditions in health workers.
      We evaluated the prevalence of minor psychiatric disorders and associated factors
      among primary healthcare workers. The study design was cross-sectional and
      services-based, in 240 primary healthcare units in 41 municipalities (counties)
      with more than 100 thousand inhabitants in seven States in the South and
      Northeast regions of Brazil. A total of 4,749 primary healthcare workers were
      interviewed, and prevalence of minor psychiatric disorders was 16%, with no
      statistical differences according to region or primary care model. The rate was
      higher in community health workers and other workers with secondary education
      (18%) and lower in health professionals with university training (10%); while
      physicians (15%) and nurses and nurse technicians (14.6%) were in an intermediate
      situation (p < 0.001). Occupational characteristics showed the strongest
      association with the occurrence of minor psychiatric disorders according to the
      adjusted analysis, suggesting that their reduction requires improvements in work
      conditions in primary healthcare and in the management of the Unified National
      Health System.

PMID- 22415185
TI  - [The Brazilian pharmaceutical industry and foreign trade: is there evidence of
      regressive specialization?].
AB  - Based on an exploratory discussion, the aim of this article is to investigate
      whether there is evidence of regressive specialization in the foreign trade
      pattern of the Brazilian pharmaceutical industry since trade liberalization in
      the 1990s. A descriptive statistical analysis drew on data for foreign trade in
      pharmaceutical and organic chemical products, available in the Aliceweb system of
      the Ministry of Development, Industry, and Foreign Trade, covering the periods
      1989-1995 and 1996-2008. The results, especially concerning trends in Brazil's
      trade with developed countries, suggest evidence of regressive specialization.

PMID- 22415186
TI  - [Evaluation of health planning activities by family health teams].
AB  - Evaluation of health planning activities adapted to the local context is an
      essential part of daily work in the Family Health Strategy (FHS). This study
      aimed to evaluate the planning activities conducted by family health teams in
      Espirito Santo State, Brazil. This was an ecological study based on secondary
      data from 241 health teams in 46 municipalities (counties) in the State that use
      the Evaluation for Quality Improvement in the Family Health Strategy (AMQ-ESF)
      form. Criteria were set for evaluating the responses by health professionals to
      the quality standards in the AMQ-ESF forms, and health planning indicators were
      listed. The responses were stratified according to the municipality's population
      size and time since implementation of the FHS and population coverage. The study
      mostly showed low adequacy rates in the teams' work processes in relation to the
      AMQ quality standards, and stratification of the variables had no influence on
      the local planning practices. Specific measures are needed to upgrade the work
      processes in the FHS.

PMID- 22415187
TI  - [The association between proximity to sports facilities and participation in
      sports among 13-year-olds in the city of Porto, Portugal].
AB  - The built environment can influence sports practice. The objective of this study
      was to examine the association between proximity (< 500m) to sports facilities
      and participation in sports. We evaluated 1,175 13-year-olds (54% girls) enrolled
      in public and private schools in Porto, Portugal. Sports activity was assessed
      using a self-completed questionnaire. The adolescents' residences and sports
      facilities were georeferenced. A matrix of distances from each residence to the
      facilities was calculated. For the majority (87%) of the adolescents, there was
      at least one sports facility close to their place of residence. No statistically
      significant differences were found in participation in sports based on proximity
      to facilities (< 500m vs. > 500m); the proportions were 44% vs. 38% (p = 0.414)
      in girls and 72% vs. 61% (p = 0.094) in boys. In conclusion, proximity to sports
      facilities was not significantly associated with participation in sports.

PMID- 22415188
TI  - [Determinants of neonatal mortality: a case-control study in Fortaleza, Ceara
      State, Brazil].
AB  - This case-control study with 132 cases and 264 controls aimed to determine
      predictors of neonatal mortality using hierarchical modeling. Cases were defined
      as newborns that died within 28 days of birth, and controls as the survivors,
      among infants of mothers living in Fortaleza, Ceara State, Brazil. Hierarchical
      logistic regression identified factors associated with neonatal death: maternal
      race, with brown/black race showing a protective effect (OR = 0.23; IC95%: 0.09
      0.56), time spent from home to the hospital > 30 minutes (OR = 3.12; 95%CI: 1.34
      7.25), time < 1h or > 10 hours between hospital admission and delivery (OR =
      2.43; 95%CI: 1.24-4.76), inadequate prenatal care (OR = 2.03; 95%CI: 1.03-3.99),
      low birth weight (OR = 14.75; 95%CI: 5.26-41.35), prematurity (OR = 3.41; 95%CI:
      1.29-8.98), and male gender (OR = 2.09; 95%CI: 1.09-4.03). In this case series,
      neonatal deaths were associated with the quality of prenatal care and direct care
      during labor.

PMID- 22415189
TI  - [Current issues regarding health surveillance of fluoride concentrations in
      foods].
AB  - This study analyzed the position of the Federal (Brazil), State (Sao Paulo), and
      municipal (Bauru, Sao Paulo) governments, civil society representatives, the
      regulated sector, and research associations concerning issues with fluoride
      content in foods. Analysis of the interviews (N = 15) used a qualitative
      methodology (collective subject discourse theory). Various central ideas were
      identified, including the need for stronger health surveillance in monitoring and
      controlling fluoride levels, educational measures, and more research in the area.
      The study concludes that the health surveillance approach to fluoride levels in
      foods is necessary, but still incipient. There is a mismatch between research
      output and surveillance. Regulation alone does not suffice to solve all the
      issues. Health risk communication and health education measures need to be
      implemented. Issues with fluoride on food labels need further research for the
      intervention to be effective.

PMID- 22415190
TI  - [Factors associated with smoking in the elderly: a health survey in Sao Paulo
      (ISA-SP)].
AB  - This article reports on smoking prevalence and associated factors in the elderly,
      based on a population-based cross-sectional study with multi-stage sampling
      including 1,954 individuals 60 years or older living in four areas of Sao Paulo
      State, Brazil. Overall smoking prevalence was 12.2%, and higher rates were
      associated with male gender, age 60-69 years, not belonging to an Evangelical
      church, lower income, low body weight, lack of leisure-time physical activity,
      depression/anxiety, and hypertension. There was a high prevalence of smokers
      among individuals with a history of stroke, cancer, and chronic obstructive
      pulmonary disease. The results point to the need for effective interventions in
      healthcare services to promote smoking cessation among the elderly, since many
      are unable to stop on their own, even when they have tobacco-related illnesses.
      Special attention should be paid to individuals that depend on the National
      Health System, since smoking prevalence is higher in underprivileged
      socioeconomic groups.

PMID- 22415191
TI  - [Cross-cultural adaptation of the Brazilian version of the Impact of Events Scale
      Revised (IES-R)].
AB  - The Impact of Events Scale-Revised (IES-R) is used to screen for post-traumatic
      stress disorder (PTSD). The aim of this study was to assess the cross-cultural
      adaptation of the IES-R. The scale was translated into Brazilian Portuguese and
      culturally adapted. Reliability and validity were evaluated in 45 individuals
      divided into three groups of 15 (without PTSD, with PTSD, and treated for PTSD).
      Reliability was evaluated using intraclass correlation coefficient - ICC and
      Cronbach's alfa. Discriminant validity was evaluated by comparing mean IES-R
      scores in the three groups. The area under the ROC curve (AUC) was evaluated to
      determine cut-offs with higher sensitivity (s) and specificity (e) using the
      clinical interview (DSM-IV) as reference. The IES-R showed good reliability (ICC
      = 1; alfa from 0.75 to 0.93). The mean IES-R scores (p < 0.05) and ROC curve had
      good discriminant validity for a cut-off of 5.6 (s = 0.80, e = 0.70 and AUC =
      0.81). The Brazilian version of IES-R showed good properties and can be a useful
      screening tool for PTSD.

PMID- 22415192
TI  - Anterior limb of the internal capsule in schizophrenia: a diffusion tensor
      tractography study.
AB  - Thalamo-cortical feedback loops play a key role in the processing and
      coordination of processing and integration of perceptual inputs and outputs, and
      disruption in this connection has long been hypothesized to contribute
      significantly to neuropsychological disturbances in schizophrenia. To test this
      hypothesis, we applied diffusion tensor tractography to 18 patients suffering
      schizophrenia and 20 control subjects. Fractional anisotropy (FA) was evaluated
      in the bilateral anterior and posterior limbs of the internal capsule, and
      correlated with clinical and neurocognitive measures. Patients diagnosed with
      schizophrenia showed significantly reduced FA bilaterally in the anterior but not
      the posterior limb of the internal capsule, compared with healthy control
      subjects. Lower FA correlated with lower scores on tests of declarative episodic
      memory in the patient group only. These findings suggest that disruptions,
      bilaterally, in thalamo-cortical connections in schizophrenia may contribute to
      disease-related impairment in the coordination of mnemonic processes of encoding
      and retrieval that are vital for efficient learning of new information.

PMID- 22415193
TI  - Local susceptibility causes diffusion alterations in patients with Alzheimer's
      disease and mild cognitive impairment.
AB  - Recent studies with positron emission tomography (PET) using the Pittsburgh
      compound B (PIB) found widespread amyloid plaque depositions in patients with
      Alzheimer's disease (AD) and mild cognitive impairment (MCI) and even in
      cognitively normal (CN) subjects. The aim of this study was to investigate
      whether the local susceptibility gradients in brain tissue alter regional
      diffusion measurements using MRI in patients with AD and MCI. Two diffusion
      tensor (DT)-MRI data sets were acquired with alternating polarities of the
      external diffusion-sensitizing gradients. Three subject groups were included: 15
      patients with AD, 18 patients with MCI and 16 CN. Maps of mean diffusivity (MD)
      and fractional anisotropy (FA) were computed separately for positive (p) and
      negative (n) polarities (pMD and nMD, pFA and nFA). Voxel-wise paired t-tests
      were performed between pMD versus nMD or between pFA versus nFA maps, separately
      for each subject group. We also investigated regions-of-interest (ROIs) in the
      brain. Based on the pair-wise comparisons, we found significant differences
      between pMD and nMD in all three groups. Results of ROI-based analyses showed
      that the non-linear behaviors of the ROI data sets were shown for all three
      groups. In conclusion, significant differences of MD maps between the two
      polarities of diffusion-sensitizing gradients were found, suggesting that the
      intrinsic background gradients may alter MD signals in specific regions. It can
      be important to take into account the effects of local gradient alterations
      during diffusion measurements in patients with AD, MCI and elderly controls.

PMID- 22415194
TI  - Downregulation of miR-27a* and miR-532-5p and upregulation of miR-146a and miR
      155 in LPS-induced RAW264.7 macrophage cells.
AB  - MicroRNAs (miRNAs) are short non-coding RNAs that are involved in the epigenetic
      regulation of cellular processes. To identify more miRNAs which are involved in
      the macrophage inflammatory response to lipopolysaccharide (LPS) stimulation and
      dissect the mechanisms more clearly, microRNA profiling of LPS-treated RAW264.7
      macrophage cells was performed by initial high-throughput array-based screen and
      further real-time RT-PCR validation; bioinformatics approaches were used to
      analyze the target genes of the differentially expressed miRNAs. Compared to the
      untreated control, two microRNAs (miR-146a and miR-155) with more than twofold
      higher expression and two microRNAs (miR-27a* and miR-532-5p) with twofold lower
      expression were detected by array-based screen, which can be validated by qRT
      PCR, and more than 1,000 candidate target genes were detected by at least of one
      of four different algorithms (TargetScan, PicTar, miRDB, and microRNA.org); with
      gene ontology classification, we were able to correlate the upregulation and
      downregulation of miRNA to the differential expression of inflammation-related
      candidate target gene during LPS-induced inflammation. Our findings may provide
      the basic information for the precise roles of miRNAs in the macrophage
      inflammatory response to LPS stimulation in the future.

PMID- 22415195
TI  - The efficiency of proanthocyanidin in an experimental pulmonary fibrosis model:
      comparison with taurine.
AB  - Pulmonary fibrosis (PF) is a progressive fatal disorder. Bleomycin (BLM) is a
      widely used chemotherapeutic agent causing PF. Numerous agents have been
      investigated to prevent the progression of PF so far, but there is still a need
      to find more efficacious agents. Proanthocyanidin (PA) is a strong antioxidant,
      the main ingredient of grape seed extract. Since PA is ready for use in practice,
      we aimed to compare the preventive effect of PA in comparison with taurine (Tau)
      in BLM-induced PF. Forty Wistar male albino rats were used in the study and were
      divided into four groups: group 1, control; group 2, BLM-induced PF group; group
      3, BLM-induced PF and treated with PA group; and group 4, BLM-induced PF and
      treated with Tau group. Treatments were begun 10 days before and continued 21
      days after BLM injection. PA and Tau effectively inhibited inflammation, edema,
      severity of fibrosis, fibrosis extension, inflammatory cell accumulation, iNOS
      staining, and hydroxyproline level as well (p < 0.05). Total histological scores
      of the PA group were similar to the control group; Tau was significantly higher
      than the control group but lower than the BLM group (p < 0.05). We believe that
      PA could be a new treatment choice for PF, but further studies need to be
      conducted to verify the findings of the current study.

PMID- 22415197
TI  - The jejunum of diarrhea-predominant irritable bowel syndrome shows molecular
      alterations in the tight junction signaling pathway that are associated with
      mucosal pathobiology and clinical manifestations.
AB  - OBJECTIVES: Diarrhea-predominant irritable bowel syndrome (IBS-D) patients show
      altered epithelial permeability and mucosal micro-inflammation in both proximal
      and distal regions of the intestine. The objective of this study was to determine
      the molecular events and mechanisms and the clinical role of upper small
      intestinal alterations. METHODS: Clinical assessment and a jejunal biopsy was
      obtained in IBS-D patients and healthy subjects. Routine histology and
      immunohistochemistry was performed in all participants to assess the number of
      mast cells (MCs) and intraepithelial lymphocytes. RNA in tissue samples was
      isolated to identify genes showing consistent differential expression by
      microarray analysis followed by pathway and network analysis in order to identify
      the biological functions of the differentially expressed genes in IBS-D. Gene and
      protein expression of tight junction (TJ) components was also assessed by
      quantitative real-time polymerase chain reaction and confocal microscopy to
      evaluate the pathways identified by gene expression analysis. RESULTS: The
      analysis reveals a strong association between the transcript signature of the
      jejunal mucosa of IBS-D and intestinal permeability, MC biology, and TJ
      signaling. The expression of zonula occludens 1 (ZO-1) was reduced in IBS-D at
      both gene and protein level, with protein redistribution from the TJ to the
      cytoplasm. Remarkably, our analysis disclosed significant correlation between ZO
      proteins, MC activation, and clinical symptoms. CONCLUSIONS: IBS-D manifestations
      are linked to molecular alterations involving MC-related dysregulation of TJ
      functioning in the jejunal mucosa.

PMID- 22415196
TI  - Obstetric trauma, pelvic floor injury and fecal incontinence: a population-based
      case-control study.
AB  - OBJECTIVES: Current concepts based on referral center data suggest that pelvic
      floor injury from obstetric trauma is a major risk factor for fecal incontinence
      (FI) in women. In contrast, a majority of community women only develop FI decades
      after vaginal delivery, and obstetric events are not independent risk factors for
      FI. However, obstetric events are imperfect surrogates for anal and pelvic floor
      injury, which is often clinically occult. Hence, the objectives of this study
      were to evaluate the relationship between prior obstetric events, pelvic floor
      injury, and FI among community women. METHODS: In this nested case-control study
      of 68 women with FI (cases; mean age 57 years) and 68 age-matched controls from a
      population-based cohort in Olmsted County, MN, pelvic floor anatomy and motion
      during voluntary contraction and defecation were assessed by magnetic resonance
      imaging. Obstetric events and bowel habits were recorded. RESULTS: By
      multivariable analysis, internal sphincter injury (cases-28%, controls-6%; odds
      ratio (OR): 8.8; 95% confidence interval (CI): 2.3-34) and reduced perineal
      descent during defecation (cases-2.6 +/- 0.2 cm, controls-3.1 +/- 0.2 cm; OR:
      1.7; 95% CI: 1.2-2.4) increased FI risk, but external sphincter injury (cases
      25%, controls-4%; P<0.005) was not independently predictive. Puborectalis injury
      was associated (P<0.05) with impaired anorectal motion during squeeze, but was
      not independently associated with FI. Grades 3-4 episiotomy (OR: 3.9; 95% CI: 1.4
      11) but not other obstetric events increased the risk for pelvic floor injury.
      Heavy smoking (>= 20 pack-years) was associated (P=0.052) with external sphincter
      atrophy. CONCLUSIONS: State-of-the-art imaging techniques reveal pelvic floor
      injury or abnormal anorectal motion in a minority of community women with FI.
      Internal sphincter injury and reduced perineal descent during defecation are
      independent risk factors for FI. In addition to grades 3-4 episiotomy, smoking
      may be a potentially preventable, risk factor for pelvic floor injury.

PMID- 22415198
TI  - Relationship between gallbladder surgery and ethnic admixture in African American
      and Hispanic American women.
AB  - OBJECTIVES: The objective of this study was to investigate whether differences in
      admixture in African American and Hispanic American adult women are associated
      with differences in gallbladder surgery. METHODS: Gallbladder surgery history on
      entry to the Women's Health Initiative's (WHI) study was used as a dichotomous
      outcome measure for this study. The proportion of European, sub-Saharan African,
      and Amerindian (AMI) admixture was estimated for 10,841 African American and
      4,620 Hispanic American women in WHI using 92 ancestry informative markers.
      Logistic regression analyses assessed the relationship between admixture and
      gallbladder surgery in WHI women (enrollment at ages >50, mean age 61 years) with
      or without adjusting for multiple covariates, including measures of adiposity,
      parity, alcohol use, and education. RESULTS: There was a significant positive
      association between AMI admixture and the frequency of gallbladder surgery in
      Hispanic Americans. The odds ratio (OR) and 95% confidence intervals (CIs) for
      AMI admixture group was OR=2.97, CI=2.01-4.38, P<10(-4). Although there were
      strong positive associations with parity and adiposity, and negative associations
      with alcohol consumption and education, accounting for these covariates did not
      remove the admixture association (OR=2.46, CI=1.62-3.73). In contrast, the effect
      of African admixture was nearly indistinguishable from that of the European
      admixture, both of which were protective in the Hispanic American group, and
      African admixture had a marginal association with decreased gallbladder surgery
      in the African American group. Measures of adiposity were associated with
      increased risk for gallbladder surgery and remained significant after accounting
      for admixture and each of the other covariates. Education level and alcohol use
      were associated with decreased risk for gallbladder disease. However, after
      accounting for the other covariates these variably remained significant.
      CONCLUSIONS: AMI admixture is strongly associated with gallbladder surgery in
      women, even after adjustment for selected risk factors for cholelithiasis.
      Additional studies to ascertain the specific genetic risk factors underlying
      these associations are warranted.

PMID- 22415199
TI  - Microalterations of esophagus in patients with non-erosive reflux disease: in
      vivo diagnosis by confocal laser endomicroscopy and its relationship with
      gastroesophageal reflux.
AB  - OBJECTIVES: Objectively diagnosing non-erosive reflux disease (NERD) is still a
      challenge. We aimed to evaluate the use of in-vivo confocal laser endomicroscopy
      (CLE) to examine the microalterations of the esophagus in patients with NERD and
      its relationship with reflux episodes monitored by multiple intraluminal
      impedance-pH (MII-pH). METHODS: Patients with gastroesophageal reflux symptoms
      completed reflux disease questionnaires. NERD was determined by negative
      gastroscopy. Patients without reflux symptoms were recruited as controls. Pilot
      clinical study was followed by prospective controlled blinded study. All subjects
      were examined by white-light mode of the endoscopy followed by the standard CLE
      mode and then MII-pH monitoring. The microalterations seen on CLE images and the
      correlation between CLE features and reflux episodes were evaluated, the
      correlation between CLE and transmission electron microscope (TEM) data was also
      analyzed. RESULTS: On CLE images, NERD patients had more intrapapillary capillary
      loops (IPCLs) per image than did controls (8.29 +/- 3.52 vs. 5.69 +/- 2.31,
      P=0.010), as well as the diameter of IPCLs (19.48 +/- 3.13 vs. 15.87 +/- 2.21
      MUm, P=0.041) and intercellular spaces of squamous cells (3.40 +/- 0.82 vs. 1.90
      +/- 0.53 MUm, P=0.042). The receiver operating characteristic analysis indicated
      that IPCLs number (optimal cutoff >6 per image, area under the curve (AUC) 0.722,
      95% confidence interval (CI) 0.592-0.853, sensitivity 67.7%, specificity 71.6%),
      IPCLs diameter (optimal cutoff >17.2 MUm, AUC 0.847, 95% CI 0.747-0.947,
      sensitivity 81%, specificity 76%), and the intercellular spaces of squamous cells
      (optimal cutoff >2.40 MUm, AUC 0.935, 95% CI 0.875-0.995, sensitivity 85.7%,
      specificity 90.5%) diagnosed NERD with reasonable accuracy. Combined features of
      dilatation of intercellular space plus increased IPCLs provided 100% specificity
      in the diagnosis of NERD patients. The intercellular spaces of squamous cells
      observed on CLE were highly related to that on TEM findings (r=0.75, P<0.001).
      Multivariate progressive regression analysis showed that acidic reflux,
      especially in the supine position, was related to the increased number and
      dilation of IPCLs in the squamous epithelium (beta=0.063, t=2.895, P=0.038 and
      beta=0.156, t=1.023, P=0.04). CONCLUSIONS: CLE represents a useful and
      potentially significant improvement over standard endoscopy to examine the
      microalterations of the esophagus in vivo. Acidic reflux is responsible for the
      microalterations in the esophagus of patients with NERD.

PMID- 22415201
TI  - Neural mechanisms of timing control in a coincident timing task.
AB  - Many ball sports such as tennis or baseball require precise temporal anticipation
      of both sensory input and motor output (i.e., receptor anticipation and effector
      anticipation, respectively) and close performance monitoring. We investigated the
      neural mechanisms underlying timing control and performance monitoring in a
      coincident timing task involving both types of anticipations. Peak force for two
      time-to-peak force (TTP) conditions-recorded with a force-sensitive key-was
      required to coincide with a specific position of a stimulus rotating either slow
      or fast on a clock face while the contingent negative variation (CNV) and the
      motor-elicited negativity were recorded. Absolute timing error was generally
      smaller for short TTP (high velocity) conditions. CNV amplitudes increased with
      both faster stimulus velocity and longer TTPs possibly reflecting increased motor
      programming efforts. In addition, the motor-elicited negativity was largest in
      the slow stimulus/short TTP condition, probably representing some forms of
      performance monitoring as well as shorter response duration. Our findings
      indicate that the coincident timing task is a good model for real-life situations
      of tool use.

PMID- 22415202
TI  - Forces, movements and reflexes produced by pushing human teeth.
AB  - Pushing a tooth results in movement of the tooth and reflex inhibition of
      activity in jaw-closing muscles. The aims of this study were to determine how
      much tooth movement is required to elicit such reflexes and whether this is
      dependent on the point of force application to the tooth. Eight experiments were
      performed on six volunteer subjects. Electromyograms (EMGs) were recorded from a
      masseter muscle while the subjects produced approximately 12.5 % of the EMG
      associated with maximal clenching. Reflexes were evoked by pushing at two
      positions (incisal and cervical) on an upper central incisor. The forces applied
      and the resulting movements of the tooth were recorded. There was a linear
      relationship between force and movement regardless of whether the force was
      incisal or cervical (Pearson's r = 0.91 and r = 0.93 respectively). There were no
      differences between the slopes or intercepts for these relationships (ANCOVA p =
      0.42, p = 0.46 respectively). There were linear relationships between the
      logarithms of force or movement and the resulting inhibitory reflexes (r = 0.81,
      0.79, 0.81 and 0.74 for incisal and cervical forces and incisal and cervical
      movements, respectively). Again, there were no significant differences between
      the slopes for these relationships (ANCOVA p = 0.75, p = 0.46 for force and
      movement, respectively). There were no significant differences between the reflex
      thresholds for incisal and cervical stimuli in terms of force (0.23 and 0.25 N,
      ANCOVA p = 0.1) or movement (9.7 and 8.5 MUm, ANCOVA p = 0.22). Thus, it appears
      that neither tooth movements nor jaw reflexes are dependent on the point of force
      application to a tooth.

PMID- 22415200
TI  - Myeloproliferation and hematopoietic stem cell dysfunction due to defective Notch
      receptor modification by O-fucose glycans.
AB  - O-fucosylglycans on Notch extracellular domain epidermal growth factor (EGF)
      repeats are critical in modulating Notch signaling by altering the sensitivity of
      Notch receptors to activation by Notch ligands. Mice lacking Notch O
      fucosylglycans display granulo-monocytic myeloproliferation, hematopoietic stem
      cell dysfunction and aberrant stem cell niche occupancy. The inability of the
      stem cells/progenitors that lack Notch O-fucosylglycans to transcribe Notch
      signaling activation is attributed by a loss of effective Notch-ligand
      interaction. These findings, in conjunction with myeloproliferation identified in
      mouse models with defective Notch cleavage or ligand endocytosis, reveal emerging
      new roles of Notch in hematopoietic stem cell biology and myeloid homeostasis.

PMID- 22415203
TI  - Increased high-density lipoprotein cholesterol is associated with a high
      prevalence of pre-hypertension and hypertension in community-dwelling persons.
AB  - The aim of this article was that high-density lipoprotein cholesterol (HDL-C)
      reduces blood vessel injury through its antioxidant and anti-inflammatory
      functions. However, the effect of HDL-C on blood pressure may be controversial.
      Therefore, the aim of this study was to address whether HDL-C level is associated
      with blood pressure, and we examined cross-sectional data from community-dwelling
      persons. A total of 859 men [58 +/- 15 (mean +/- standard deviation); 20-89
      (range) (years) and 1,169 women (61 +/- 13; 19-88 years)] participants not on
      medication for hypertension were recruited from a single community at the time of
      their annual health examination. We examined the relationship between
      cardiovascular risk factors and blood pressure status. Multiple linear regression
      analysis using systolic blood pressure (SBP) and diastolic blood pressure (DBP)
      as an objective variable showed that HDL-C was significantly and independently
      associated with both SBP (beta = 0.138), and DBP (beta = 0.144). Compared to
      normotensive participants with the lowest quartile of HDL-C, multivariate
      adjusted odds ratio (OR) for pre-hypertension was 1.72 (1.22-2.45) for the second
      quartile, 1.51 (1.07-2.15) for the third quartile, and 1.52 (1.04-2.22) for the
      highest quartile. Moreover, compared with normotensive participants with the
      lowest quartile, the multivariate-adjusted ORs for hypertension were 2.37 (1.63
      3.45), 2.24 (1.54-3.28), 3.15 (2.10-4.74), respectively. There were no
      interactions between the two groups stratified by gender, age, BMI, drinking
      status, TG, FPG, and medication. Therefore, we concluded that HDL-C levels were
      positively associated with blood pressure in Japanese dwelling-community persons.

PMID- 22415204
TI  - Effects of guanidinium ions on the conformational structure of glucose oxidase
      studied by electrochemistry, spectroscopy, and theoretical calculations: towards
      developing a chemical-induced protein conformation assay.
AB  - Understanding conformation transitions of proteins in the presence of a chemical
      denaturant is a topic of great interest because the rich information contained in
      chemical unfolding is of fundamental importance for proteomic and pharmaceutical
      research. In this work, the conformational structure changes of glucose oxidase
      (GOx) induced by guanidinium ions (Gdm(+)) were studied in detail by a
      combination of electrochemical methods, various spectroscopic techniques
      including ultraviolet-visible (UV-vis) absorption, fluorescence, Fourier
      transform infrared (FTIR), and circular dichroism (CD) spectroscopy, molecular
      dynamics (MD) simulations, and density functional theory (DFT) calculations with
      the purpose of revealing the mechanism of chemical unfolding of proteins. The
      results indicated that GOx underwent substantial conformational changes both at
      the secondary and tertiary structure levels after interacting with Gdm(+) ions.
      The interaction of GOx with the chemical denaturant resulted in a disturbance of
      the structure of the flavin prosthetic group (FAD moiety) that induced the moiety
      to become less exposed to solvent than that in the native protein molecule. The
      calculation from quantitative second-derivative infrared and CD spectra showed
      that Gdm(+) ions induced the conversion of alpha-helix to beta-sheet structures.
      MD simulations and DFT calculations revealed that Gdm(+) ions could enter the
      active pocket of the GOx molecule and interact with the FAD group, leading to a
      significant alteration in the structural characteristics and hydrogen bond
      networks formed between FAD and the surrounding amino acid residues. These
      alterations in the conformational structure of GOx resulted in a significant
      decrease in the catalytic activity of the enzyme to glucose oxidation. The study
      essentially provides an effective way for investigating the mechanism of chemical
      denaturant-induced protein unfolding, and this approach can be used for assessing
      the effect of drug molecules on proteins.

PMID- 22415205
TI  - Perspectives of adolescent siblings of children with Down syndrome who have
      multiple health problems.
AB  - Authors of this qualitative descriptive study interviewed 21 adolescent siblings
      of children with Down syndrome (DS) who also had additional health problems rated
      as requiring extensive care by parents. Analysis revealed positive/negative
      aspects of the experience; however, participants emphasized the positive rather
      than negative experiences and focused more on the fact that the child had DS
      rather than health problems requiring additional care. Most said they would not
      change anything about their experience and did not believe the child with DS
      would ever live independently. They did, however, acknowledge their family was
      affected by the caregiving needs of the child which often required extra
      vigilance or specific care depending on the health problem. Information gained
      can help improve understanding of adolescent sibling perceptions about living
      with a child with DS who also requires additional care because of ongoing health
      problems so more appropriate and individualized nursing interventions can be
      provided.

PMID- 22415206
TI  - The development of Cam-type deformity in adolescent and young male soccer
      players.
AB  - BACKGROUND: Cam impingement is a well-recognized cause of hip pain and might
      cause osteoarthritis of the hip. Clinically, cam impingement is mostly observed
      in young, active male patients, but only a few studies have focused on the
      manifestation of cam-type deformities during skeletal development. PURPOSE: To
      determine the age of onset and prevalence of cam-type deformities in young male
      soccer players versus controls. STUDY DESIGN: Cross-sectional study; Level of
      evidence, 3. METHODS: In this study, 89 elite preprofessional soccer players and
      92 controls aged 12 to 19 years were included. In the soccer players, range of
      motion and impingement tests were performed. Both an anteroposterior (AP) pelvic
      radiograph and a frog-leg lateral radiograph of the hip were obtained according
      to a standardized protocol. Controls with both an AP pelvic and a frog-leg
      lateral radiograph and no hip disorders were obtained from radiology databases.
      The alpha angle was automatically determined in all radiographs, using a
      threshold value of 60 degrees  to define a cam-type deformity. Further, all
      radiographs were scored using a 3-point scoring system. The anterosuperior head
      neck junction was classified as (1) normal, (2) flattened, or (3) having a
      prominence. Differences in prevalence were tested using logistic regression.
      Differences in range of motion were calculated using generalized estimating
      equations. RESULTS: An alpha angle >60 degrees  was already found at the age of
      12 years in some soccer players and controls. A cam-type deformity defined by
      alpha angle tended to be more prevalent in soccer players (26%) than in controls
      (17%; P = .31). In 13% of soccer players, a prominence was visible on radiographs
      and was first seen at the age of 13 years. The anterosuperior flattening (56% vs
      18%, P = .0001) and prominence (13% vs 0%, P < .03) were more prevalent in soccer
      players than in controls. CONCLUSION: Cam-type deformities were recognizable and
      present from the age of 13 years and were more prevalent in soccer players than
      in their nonathletic peers. Cam-type deformity develops during adolescence and is
      likely to be influenced by high-impact sports practice.

PMID- 22415207
TI  - Axial load-bearing capacity of an osteochondral autograft stabilized with a
      resorbable osteoconductive bone cement compared with a press-fit graft in a
      bovine model.
AB  - BACKGROUND: Osteochondral autografts in mosaicplasty are inserted in a press-fit
      fashion, and hence, patients are kept nonweightbearing for up to 2 months after
      surgery to allow bone healing and prevent complications. Very little has been
      published regarding alternative fixation techniques of those grafts. HYPOTHESIS:
      Osteochondral autografts stabilized with a resorbable osteoconductive bone cement
      would have a greater load-bearing capacity than standard press-fit grafts. STUDY
      DESIGN: Controlled laboratory study. METHODS: Biomechanical testing was conducted
      on 8 pairs of cadaveric bovine distal femurs. For the first 4 pairs, 6 single
      osteochondral autografts were inserted in a press-fit fashion on one femur. On
      the contralateral femur, 6 grafts were stabilized with a calcium triglyceride
      osteoconductive bone cement. For the 4 remaining pairs of femurs, 4 groups of 3
      adjacent press-fit grafts were inserted on one femur, whereas on the
      contralateral femur, grafts were cemented. After a maturation period of 48 hours,
      axial loading was applied on all single grafts and on the middle graft of each 3
      in-a-row series. RESULTS: For the single-graft configuration, median loads
      required to sink the press-fit and cemented grafts by 2 and 3 mm were 281.87 N
      versus 345.56 N (P = .015) and 336.29 N versus 454.08 N (P = .018), respectively.
      For the 3-in-a-row configuration, median loads required to sink the press-fit and
      cemented grafts by 2 and 3 mm were 260.31 N versus 353.47 N (P = .035) and 384.83
      N versus 455.68 N (P = .029), respectively. CONCLUSION: Fixation of osteochondral
      grafts using bone cement appears to improve immediate stability over the original
      mosaicplasty technique for both single- and multiple-graft configurations.
      CLINICAL RELEVANCE: Achieving greater primary stability of osteochondral grafts
      could potentially accelerate postoperative recovery, allowing early weightbearing
      and physical therapy.

PMID- 22415208
TI  - The FIFA 11+ program is effective in preventing injuries in elite male basketball
      players: a cluster randomized controlled trial.
AB  - BACKGROUND: Recently, structured training programs for sports injury prevention
      ("The 11" and "The 11+") have been validated in soccer. The FIFA 11+ program has
      not been evaluated in basketball. HYPOTHESIS: The FIFA 11+ program is effective
      in reducing the rates of injury in male basketball players. STUDY DESIGN:
      Randomized controlled trial; Level of evidence, 1. METHODS: The authors
      randomized 11 teams of the same club. Seven teams were allocated to the
      intervention group (80 players; mean [SD] age 13.5 [2.3] years), and 4 teams were
      allocated to the control group (41 players; mean [SD] age 15.2 [4.6] years). The
      authors conducted an injury surveillance program during a 9-month season. The
      primary outcome was any injury to the athletes. The secondary outcome was any
      injury to the lower extremity (foot, ankle, lower leg, knee, thigh, groin, and
      hip). They included an analysis of the type of exposure (match or training),
      injury location in the body, and type of injury (acute or overuse). RESULTS:
      During the 9-month season, 23 (19%) of the 121 players included in the study
      sustained a total of 31 injuries (14 in the intervention group and 17 in the
      control group). In the intervention group, injury rates per 1000 athlete
      exposures were lower than those in the control group, with statistical
      significance, for overall injuries (0.95 vs 2.16; P = .0004), training injuries
      (0.14 vs 0.76; P = .007), lower extremity injuries (0.68 vs 1.4; P = .022), acute
      injuries (0.61 vs 1.91; P < .0001), and severe injuries (0 vs 0.51; P = .004).
      The intervention group also had statistically significant lower injury rates for
      trunk (0.07 vs 0.51; P = .013), leg (0 vs 0.38; P = .007), and hip and groin (0
      vs 0.25; P = .023) compared with the control group. There was no statistically
      significant difference in match injuries, knee injuries, ankle injuries, and
      overuse injuries between 2 groups. The most frequent acute injury diagnoses were
      ligament sprains (0.41 and 0.38 in the intervention and control groups,
      respectively; P < .006) and contractures (0.76 and 0.07 in the control and
      intervention groups, respectively; P < .003). CONCLUSION: The FIFA 11+ warm-up
      program is effective in reducing the rates of injuries in elite male basketball
      players.

PMID- 22415209
TI  - Tibial tubercle-posterior cruciate ligament distance: a new measurement to define
      the position of the tibial tubercle in patients with patellar dislocation.
AB  - BACKGROUND: In patients with patellar instability, a pathological tibial tubercle
      trochlear groove (TT-TG) distance is a risk factor. However, the TT-TG distance
      gives no information about the location of the malformation. HYPOTHESIS: Not all
      patients with a pathological TT-TG distance (>=20 mm) had lateralization of the
      tibial tubercle. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2.
      METHODS: Fifty-eight knees in 49 patients with 2 or more patellar dislocations
      and 60 knees in 30 volunteers with no history of dislocation were analyzed using
      magnetic resonance imaging (MRI). The tibial tubercle-posterior cruciate ligament
      (TT-PCL) distance was defined as the mediolateral distance between the tibial
      tubercle midpoint and the medial border of the posterior cruciate ligament. The
      distance was measured parallel to the dorsal aspect of the proximal tibia (dorsal
      tibia condylar line). Three observers performed the measurements. Significant
      differences in the TT-PCL distance between the patient and the control group were
      estimated using an unpaired t test. The inter- and intraobserver variability of
      the measurement was performed. RESULTS: The intraclass correlation coefficients
      for inter- and intraobserver variability of the TT-PCL distance were higher than
      0.74 and 0.93, respectively. A statistically significant difference (P < .05) was
      found between the TT-PCL distance in the control group (mean [SD], 18.4 [3.35]
      mm) and in patients (21.9 [4.30] mm). The mean (SD) TT-TG was 18.9 (5.16) mm in
      the patient group and 11.9 (4.67) mm in the control group (P < .05). In the
      control group, 95% had a TT-PCL distance <24 mm. In the patient group, 22 of 58
      knee joints (38%) had a TT-PCL distance >=24 mm. Seventeen of 40 knee joints
      (43%) with a TT-TG distance >=20 mm had a TT-PCL distance <24 mm. CONCLUSION:
      Only 57% of the patients with a pathological TT-TG distance (>=20 mm) had
      lateralization of the tibial tubercle in relation to the posterior cruciate
      ligament. The TT-PCL distance is an alternative method for determining the
      position of the tibial tubercle.

PMID- 22415210
TI  - Comparison of partial versus complete arthroscopic repair of massive rotator cuff
      tears.
AB  - BACKGROUND: Complete repair of massive rotator cuff tears can be limited by
      tendon retraction and poor tissue quality. When a complete repair cannot be
      accomplished, a significant partial repair may be possible. HYPOTHESIS: A partial
      repair will yield comparable outcomes to complete repair of massive rotator cuff
      tears in this specific patient population. STUDY DESIGN: Cohort study; Level of
      evidence, 3. METHODS: All consecutive arthroscopic rotator cuff repairs done at
      the authors' institution over a 2-year period were identified. A retrospective
      chart review was performed. Inclusion criteria required that each patient have a
      massive rotator cuff tear (30 cm(2) or greater). Patients were categorized as
      either partial or complete repair. The University of California, Los Angeles
      (UCLA) shoulder scores were used to measure patient outcomes at an average follow
      up of 24 months (10-40 months). RESULTS: Of 1128 consecutive arthroscopic rotator
      cuff repairs, 97 (9%) patients were noted intraoperatively to have massive tears
      measuring 30 cm(2) or greater. Complete repair was achieved in 52 patients,
      whereas partial repair was possible in 45 patients. Eleven patients were lost to
      follow-up. The 41 remaining patients with only partial repair achieved a
      postoperative mean UCLA score of 29.49, and the 45 patients with complete repair
      achieved a mean UCLA score of 29.64, yielding significant improvement in both the
      partial repair group (P = .0001) and the complete repair group (P = .0001)
      compared with preoperative UCLA scores. However, no statistically significant
      differences in postoperative outcomes were noted when the 2 groups were compared
      with one another (P = .89). CONCLUSION: Partial repair of massive rotator cuff
      tears yielded outcomes comparable with complete repair of massive tears.

PMID- 22415211
TI  - Clock test deficits related to the global cognitive state in Alzheimer's and
      Parkinson's disease.
AB  - BACKGROUND/AIMS: Clock drawing (CD) seems to be impaired quite early in the
      process of cognitive decline in Parkinson's disease (PD). METHODS: We assessed
      performance on the CD test (CDT), clock setting test (CST) and clock reading test
      (CRT) in 32 elderly healthy controls, 41 patients with PD, 23 patients with
      amnestic mild cognitive impairment (aMCI) and 40 patients with Alzheimer's
      dementia (AD). Our focus was on comparing the performance of PD and aMCI/AD
      patients in relation to their global cognitive states (operationalized by the
      Mini Mental Status Examination). We also analyzed qualitative differences in
      errors of drawing, setting and reading clocks. RESULTS: We found that performance
      in CDT, but not in the CST or CRT, was impaired earlier in PD than in aMCI/AD.
      Incorrect placement of the minute hand was the most prominent error in both
      patient groups. We found no specific influence of visuospatial dysfunction in PD
      on clock drawing. CONCLUSION: Our findings suggest that executive function
      related to retrieval of semantic memory about the minute hand is compromised
      early in PD.

PMID- 22415212
TI  - Influence of methanandamide and CGRP on potassium currents in smooth muscle cells
      of small mesenteric arteries.
AB  - Cannabinoids have potent vasodilatory actions in a variety of vascular
      preparations. Their mechanism of action, however, is complex. Apart from acting
      on vascular smooth muscle or endothelial cannabinoid receptors, several studies
      point to the activation of type 1 vanilloid (TRPV1) receptors on primary afferent
      perivascular nerves, stimulating the release of calcitonin gene-related peptide
      (CGRP). In the present study, the direct influence of the cannabinoid
      methanandamide and the neuropeptide CGRP on the membrane potassium ion (K(+))
      currents of rat mesenteric myocytes was explored. Methanandamide (10 MUM)
      decreased outward K(+) currents, an effect similar to that observed in smooth
      muscle cells from the rat aorta. Conversely, CGRP (10 nM) significantly increased
      whole-cell K(+) currents and this effect was abolished by preexposure to
      tetraethylammonium chloride (1 mM) or iberiotoxin (100 nM), inhibitors of large
      conductance calcium-dependent K (BK(Ca)) channels but not by glibenclamide (10
      MUM), an inhibitor of ATP-dependent K channels. In the presence of the CGRP
      receptor antagonist CGRP(8-37) (100 nM), the adenylyl cyclase inhibitor SQ22536
      (100 MUM), or the protein kinase A inhibitor Rp-cAMPS (10 MUM), CGRP had no
      effect. These findings show that methanandamide does not increase membrane K(+)
      currents in smooth muscle cells of small mesenteric arteries, supporting an
      indirect mechanism for the reported hyperpolarizing influence in this vessel.
      Moreover, CGRP acts directly on these smooth muscle cells by increasing BK(Ca)
      channel activity in a CGRP receptor and cyclic adenosine monophosphate-dependent
      way. Collectively, these data indicate that methanandamide relaxes and
      hyperpolarizes intact mesenteric vessels by releasing CGRP from perivascular
      nerves.

PMID- 22415213
TI  - Postnatal developmental decline in IK1 in mouse ventricular myocytes isolated by
      the Langendorff perfusion method: comparison with the chunk method.
AB  - Expression and function of cardiac ion channels exhibit postnatal developmental
      changes, which, however, has not yet been proven in ventricular myocytes isolated
      using similar techniques. In this study, ventricular myocytes were enzymatically
      dissociated from mouse heart at different postnatal ages (including postnatal day
      0) by similar techniques using Langendorff perfusion. Whole-cell patch-clamp
      experiments were performed to record action potentials, I (K1), I (Kr), I (Kur),
      I (ss), and I (Ca,L), in ventricular myocytes freshly isolated from postnatal
      days 0, 7, and 14 and adult mice. Viable ventricular myocytes of day-0 mouse
      heart exhibited spindle-shaped appearance having cell length of approximately 50
      MUm, which gradually developed to a rod-shaped one having clear cross striation
      with cell length of approximately 120 MUm (adult). The action potential duration
      markedly shortened, while the resting membrane potential depolarized to a small
      but significant extent during postnatal development. I (K1) density was maximal
      in postnatal day-0 ventricular myocytes and gradually decreased during
      development, which was accompanied by postnatal depolarization of resting
      membrane potential. However, I (K1) density was markedly decreased by
      approximately 80% in postnatal day-0 ventricular myocytes, when isolated by the
      chunk method. Quantitative real-time polymerase chain reaction (PCR) and western
      blot analyses demonstrated higher Kir2.3 expression but lower expression levels
      of Kir2.1 and Kir2.2 in day-0 mouse ventricles, compared with those of day-14 and
      adult mouse ventricles. Whereas I (Kr) exhibited marked decrease during postnatal
      development, I (Kur), I (ss), and I (Ca,L) exhibited postnatal developmental
      increase. The present cell isolation method using the Langendorff perfusion thus
      found that, in mouse ventricles, I (K1) exhibited postnatal developmental
      decrease, associated with depolarization of resting potential.

PMID- 22415214
TI  - Cell type influences the molecular mechanisms involved in hormonal regulation of
      ERG K+ channels.
AB  - While the thyrotropin-releasing hormone (TRH) effect of raising intracellular
      Ca(2+) levels has been shown to rely on G(q/11) and PLC activation, the molecular
      mechanisms involved in the regulation of ERG K(+) channels by TRH are still
      partially unknown. We have analysed the effects of betagamma scavengers, Akt/PKB
      inactivation, and TRH receptor (TRH-R) overexpression on such regulation in
      native and heterologous expression cell systems. In native rat pituitary GH(3)
      cells beta-ARK/CT, Galpha(t), and phosducin significantly reduced TRH inhibition
      of rERG currents, whereas in HEK-H36/T1 cells permanently expressing TRH-R and
      hERG, neither of the betagamma scavengers affected the TRH-induced shift in V
      (1/2). Use of specific siRNAs to knock Akt/PKB expression down abolished the TRH
      effect on HEK-H36/T1 cell hERG, but not on rERG from GH(3) cells. Indeed,
      wortmannin or long insulin pretreatment also blocked TRH regulation of ERG
      currents in HEK-H36/T1 but not in GH(3) cells. To determine whether these
      differences could be related to the amount of TRH-Rs in the cell, we studied the
      TRH concentration dependence of the Ca(2+) and ERG responses in GH(3) cells
      overexpressing the receptors. The data indicated that independent of the receptor
      number additional cellular factor(s) contribute differently to couple the TRH-R
      to hERG channel modulation in HEK-H36/T1 cells. We conclude that regulation of
      ERG currents by TRH and its receptor is transduced in GH(3) and HEK-H36/T1 cell
      systems through common and different elements, and hence that the cell type
      influences the signalling pathways involved in the TRH-evoked responses.

PMID- 22415215
TI  - Endoplasmic reticulum-mitochondria coupling: local Ca2+ signalling with
      functional consequences.
AB  - Plasma membrane store-operated Ca2+ release-activated Ca2+ (CRAC) channels are a
      widespread and conserved Ca2+ influx pathway, driving activation of a range of
      spatially and temporally distinct cellular responses. Although CRAC channels are
      activated by the loss of Ca2+ from the endoplasmic reticulum, their gating is
      regulated by mitochondria. Through their ability to buffer cytoplasmic Ca2+,
      mitochondria take up Ca2+ released from the endoplasmic reticulum by InsP3
      receptors, leading to more extensive store depletion and stronger activation of
      CRAC channels. Mitochondria also buffer Ca2+ that enters through CRAC channels,
      reducing Ca2+-dependent slow inactivation of the channels. In addition,
      depolarised mitochondria impair movement of the CRAC channel activating protein
      STIM1 across the endoplasmic reticulum membrane. Because they regulate CRAC
      channel activity, particularly Ca2+-dependent slow inactivation, mitochondria
      influence CRAC channel-driven enzyme activation, secretion and gene expression.
      Mitochondrial regulation of CRAC channels therefore provides an important control
      element to the regulation of intracellular Ca2+ signalling.

PMID- 22415216
TI  - Osteopathology induced by bisphosphonates and dental implants: clinical
      observations.
AB  - OBJECTIVES: Although there are many reports about risk factors for the
      development of BP-associated osteonecrosis of the jaws, the role of dental
      implants as a local risk factor is still discussed, especially in patients with
      oral BP treatment. Until now, a few case reports and surveys display a possible
      minor risk in patients with oral BP therapy, whereas the avoidance of implant
      placement is generally accepted in patients with intravenous BP therapy. PATIENT
      AND METHODS: In this study, the cases of 14 patients with osteonecrosis of the
      jaws in association with BP therapy and dental implant placement were analyzed
      carefully with a detailed literature review. RESULTS: Of 14 patients, nine had
      underlying malignant disease and five patients had osteoporosis. In ten patients,
      implants were placed either in the posterior mandible or maxilla; the mean
      interval between implant insertion and disease onset was 20.9 months. Pain (n12)
      and signs of infection (n10) were the most common symptoms. Histologically, signs
      of infection were found in nine of 11 analyzed patients with presence of
      Actinomyces in six patients. Two patients turned out to have infiltration of
      underlying malignant disease. CONCLUSIONS: Posteriorly placed implants seem to be
      of higher risk of development of osteonecrosis of the jaws. Not only the implant
      placement but also the inserted implant itself seems to be a continuous risk
      factor. CLINICAL RELEVANCE: The herein elaborated risk factors help dentists plan
      dental rehabilitation with implants in this high-risk group of patients and
      indicate careful and regular dental recall.

PMID- 22415217
TI  - The role of unfinished root canal treatment in odontogenic maxillofacial
      infections requiring hospital care.
AB  - OBJECTIVES: The aim of this study was to evaluate clinical and radiological
      findings and the role of periapical infection and antecedent dental treatment of
      infected focus teeth in odontogenic maxillofacial abscesses requiring hospital
      care. MATERIALS AND METHODS: In this retrospective cohort study, we evaluated
      medical records and panoramic radiographs during the hospital stay of patients (n
      = 60) admitted due to odontogenic maxillofacial infection originating from
      periapical periodontitis. RESULTS: Twenty-three (38 %) patients had received
      endodontic treatment and ten (17 %) other acute dental treatment. Twenty-seven
      (45 %) had not visited the dentist in the near past. Median age of the patients
      was 45 (range 20-88) years and 60 % were males. Unfinished root canal treatment
      (RCT) was the major risk factor for hospitalisation in 16 (27 %) of the 60 cases
      (p = .0065). Completed RCT was the source only in 7 (12 %) of the 60 cases. Two
      of these RCTs were adequate and five inadequate. CONCLUSIONS: The initiation of
      inadequate or incomplete primary RCT of acute periapical periodontitis appears to
      open a risk window for locally invasive spread of infection with local abscess
      formation and systemic symptoms. Thereafter, the quality of the completed RCT
      appears to have minor impact. However, a considerable proportion of the patients
      had not received any dental treatment confirming the importance of good dental
      health. Thus, thorough canal debridement during the first session is essential
      for minimising the risk for spread of infection in addition to incision and
      drainage of the abscess. If this cannot be achieved, tooth extraction should be
      considered. CLINICAL RELEVANCE: Incomplete or inadequate canal debridement and
      drainage of the abscess may increase the risk for spread of endodontic infection.

PMID- 22415218
TI  - EGCG blocks TGFbeta1-induced CCN2 by suppressing JNK and p38 in buccal
      fibroblasts.
AB  - OBJECTIVES: Transforming growth factor beta (TGFbeta) has been suggested as the
      main trigger for the increased collagen production and decreased matrix
      degradation pathways in oral submucous fibrosis (OSF). Connective tissue growth
      factor (CTGF/CCN2) and cyclooxygenase-2 (COX-2) were found to overexpress in OSF.
      The aim of this study was to investigate the molecular mechanism underlying the
      TGFbeta-induced CCN2 expressions in human buccal mucosal fibroblasts (BMFs) to
      identify the potential targets for drug intervention or chemoprevention of OSF.
      MATERIALS AND METHODS: TGFbeta-induced CCN2 expression and its signaling pathways
      were assessed by Western blot analyses in BMFs. RESULTS: TGFbeta1 stimulated CCN2
      synthesis in BMFs. Pretreatment with c-Jun NH(2)-terminal kinase (JNK) inhibitor
      SP600125, p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, and
      activin receptor-like kinase 5 (ALK5) inhibitor SB431542 significantly reduced
      TGFbeta1-induced CCN2 synthesis. Epigallocatechin-3-gallate (EGCG) completely
      blocked TGFbeta1-induced CCN2 synthesis by inhibiting the phosphorylation of JNK
      and p38 MAPK. Prostaglandin E(2) (PGE(2)) inhibited the TGFbeta1-induced CCN2
      synthesis in human fetal lung fibroblasts IMR90 but not in BMFs. CONCLUSIONS: The
      TGFbeta1-induced CCN2 synthesis in BMFs could be mediated by the ALK5, JNK, and
      p38 MAPK pathways. EGCG blocks TGFbeta1-induced CCN2 by suppressing JNK and p38
      in BMFs. CLINICAL RELEVANCE: The exceptional signal transduction pathways of
      TGFbeta1-induced CCN2 production in BMFs contribute to the resistance of PGE(2)
      downregulation of CCN2 expression; therefore, the CTGF/CCN2 levels are maintained
      in the OSF tissues in the presence of COX-2. EGCG may serve as a useful agent in
      controlling OSF.

PMID- 22415219
TI  - Prenatal diagnosis of 2q32 deletion syndrome characterized by multiple segmental
      deletions and complex chromosomal rearrangement involving chromosomes 2, 5 and 7.
AB  - This is the first case of 2q32 microdeletion syndrome diagnosed prenatally and
      followed throughout the pregnancy. The pregnancy was complicated by fetal club
      feet, ventriculomegaly, intrauterine growth retardation and polyhydramnios. This
      is a unique and highly complicated prenatal diagnosis case of a de novo complex
      chromosomal rearrangement involving chromosomes 2, 5 and 7 with 15 breaks and
      multiple interstitial 2q deletions, resulting in the 2q32 microdeletion syndrome.
      The delineation of the karyotype in this case and origin of the pathology
      required the use of multiple genetic technologies including conventional
      cytogenetics, fluorescence in situ hybridization, single-nucleotide polymorphism
      array and array comparative genomic hybridization.

PMID- 22415220
TI  - Immunohistochemical detection of glypican-5 in paraffin-embedded material: an
      optimized method for a novel research antibody.
AB  - Glypican-5 (GPC5) is a cell surface heparan sulfate proteoglycan and 1 of 6
      closely related members of the glypican family in mammals. Glypicans are
      predominantly expressed during development in cell-specific and tissue-specific
      contexts, and the expression of some is linked to developmental disorders and
      several visceral malignancies. We have previously shown that the region of
      amplification at 13q31.3 in a subset of rhabdomyosarcomas contains the GPC5
      locus, and by copy number and gene expression analyses, that GPC5 is consistently
      expressed and upregulated in amplified tumors. As the immunohistochemical profile
      of GPC5 is untested, our aim was to optimize a commercially available anti-human
      GPC5 antibody for immunohistochemical use in formalin-fixed and paraffin-embedded
      (FFPE) tissue. Quantitative real-time polymerase chain reaction analyses of
      normal tissue samples indicated that the brain and testis highly expressed GPC5.
      High protein expression in these tissues and a cell line constructed to
      overexpress GPC5 were demonstrated by Western blotting. These normal tissues and
      the isogenic cell line were FFPE, and immunohistochemical expression of GPC5 was
      assessed using different methods of antigen retrieval, detection, and primary
      antibody concentration. The optimum conditions for detection were by heat-induced
      antigen retrieval, in sodium citrate buffer at pH 6. Enzyme-mediated retrieval
      did not produce effective detection, producing weaker, less well-localized GPC5
      expression. We demonstrate that anti-human GPC5 antibody is amenable to use in
      FFPE tissue and with the optimized protocol we describe shows specific cellular
      localization and good staining intensity with minimal background staining.

PMID- 22415221
TI  - The composition of the cuticular and internal free fatty acids and alcohols from
      Lucilia sericata males and females.
AB  - GC, GC-MS, and HPLC-LLSD analyses were used to identify and quantify cuticular
      and internal lipids in males and females of the blow-fly (Lucilia sericata).
      Sixteen free fatty acids, seven alcohols and cholesterol were identified and
      quantitatively determined in the cuticular lipids of L. sericata. Cuticular fatty
      acids ranged from C(6) to C(20) and included unsaturated entities such as 16:1n
      9, 18:1n-9, 20:4n-3 and 20:5n-3. Cuticular alcohols (only saturated and even
      numbered) ranged from C(12) to C(20) in males and C(10) to C(22) in females. Only
      one sterol was found in the cuticular lipids of both males and females. 23 free
      fatty acids, five alcohols and cholesterol were identified in the internal
      lipids. Internal fatty acids were present in large amounts-7.4 mg/g (female) and
      10.1 mg/g (male). Only traces of internal alcohols (from C(14) to C(26) in males,
      from C(14) to C(22) in females) were found in L. sericata. Large amounts of
      internal cholesterol were identified in L. sericata males and females (0.49 and
      0.97 mg/g of the insect body, respectively).

PMID- 22415222
TI  - Influence of heart failure etiology on the effect of upgrading from right
      ventricular apical to biventricular or bifocal pacing in patients with permanent
      atrial fibrillation and advanced heart failure.
AB  - INTRODUCTION: Chronic heart failure (HF) results from various disease processes.
      There are no data on the effect of the etiology of HF on the improvement after
      pacemaker upgrade. OBJECTIVES The aim of the study was to assess changes in
      various parameters in patients with ischemic (IC) and nonischemic (NIC)
      cardiomyopathy after pacemaker upgrade in pacemaker-dependent patients with
      permanent atrial fibrillation, in the course of advanced HF during 12-month
      follow-up. PATIENTS AND METHODS: The study involved 34 patients who underwent an
      upgrade from right ventricular apical to biventricular or bifocal right
      ventricular pacing. In each patient, 12-lead electrocardiography, transthoracic
      echocardiography, 6-minute walking test, and the measurement of brain natriuretic
      peptide levels were performed. Ischemic etiology of HF was confirmed in 25
      subjects. The subgroups of cardiomyopathy were compared in terms of the
      improvement in relative and absolute values of the parameters at 6 and 12 months.
      RESULTS: At baseline, the subgroups did not differ significantly in demographic
      data and the measured parameters. All patients completed the first period of
      follow-up showing clinical improvement after pacemaker upgrade. A significantly
      greater relative increase in the left ventricular ejection fraction was observed
      in the NIC subgroup at 6 months. The whole 12-month follow-up period was
      completed by a similar percentage of the IC and NIC patients (76% vs. 88.9%; P =
      0.73). In the IC subgroup, a greater degree of mitral regurgitation was observed.
      CONCLUSIONS: Patients with IC or NIC who underwent an upgrade from right
      ventricular apical to biventricular or bifocal right ventricular pacing and
      completed a 12-month follow-up did not differ in clinical improvement.
      Significant differences were observed in echocardiographic parameters.

PMID- 22415223
TI  - Can Minnesota Multiphasic Personality Inventory-2 predict response to selective
      serotonin reuptake inhibitors in depressed outpatients?
AB  - There is growing evidence that individual differences among patients with major
      depressive disorder (MDD) on psychological and demographic measures may predict
      the therapeutic response to selective serotonin reuptake inhibitors (SSRIs). In
      this retrospective chart review, 108 outpatients with current major depressive
      episodes were treated with citalopram, paroxetine, or fluvoxamine. The Hamilton
      Depression Rating Scale and the Minnesota Multiphasic Personality Inventory-2
      were administered before and after 8 weeks of SSRIs treatment. Clinical response
      was defined as a 50% or greater decrease in the 17-item Hamilton Depression
      Rating Scale total score (final visit minus baseline). This naturalistic short
      term follow-up outcome study demonstrates that among depressive outpatients who
      responded to an 8-week trial, 57.4% achieved a good response to SSRIs.
      Statistical analysis showed that SSRI treatment may be 3.03 times more
      advantageous for MDD outpatients who are younger than 39 years. The patients with
      an elevated score of above 66T on the Social Introversion Minnesota Multiphasic
      Personality Inventory-2 scale are approximately 0.37 times as likely to be SSRI
      responders as are patients with a Social Introversion score less than 66T. Thus,
      it seems that in MDD outpatient age is the strongest predictor of response to
      SSRIs.

PMID- 22415224
TI  - Missing the dog that failed to bark in the nighttime: on the overestimation of
      occurrences over non-occurrences in hypothesis testing.
AB  - In three studies, we investigated whether and to what extent the evaluation of
      two mutually exclusive hypotheses is affected by a feature-positive effect,
      wherein present clues are weighted more than absent clues. Participants (N = 126)
      were presented with abstract problems concerning the most likely provenance of a
      card that was drawn from one of two decks. We factored the correct response (the
      hypothesis favored by the consideration of all clues) and the ratio of present-to
      absent features in each set of observations. Furthermore, across the studies, we
      manipulated the presentation format of the features' probabilities by providing
      the probability distributions of occurrences (Study 1), non-occurrences (Study 3)
      or both (Study 2). In all studies, both participant preference and accuracy were
      mostly determined by an over-reliance on present features. Moreover, across
      participants, both confidence in the responses and the informativeness of the
      present clues correlated positively with the number of responses given in line
      with an exclusive consideration of present features. These results were mostly
      independent of both the rarity of the absent clues and the presentation format.
      We concluded that the feature-positive effect influences hypothesis evaluation,
      and we discussed the implications for confirmation bias.

PMID- 22415225
TI  - Poly(I:C) treatment influences the expression of calreticulin and profilin-1 in a
      human HNSCC cell line: a proteomic study.
AB  - Polyinosinic:polycytidylic acid (poly (I:C)) has been formerly known to be an
      interferon inducer but the mechanism of its action was not revealed until the
      discovery of Toll-like receptors (TLRs). TLRs are members of transmembrane
      proteins that recognize conserved molecular motifs of viral and bacterial origin
      and initiate innate immune response. Recent studies have shown that they are also
      expressed on tumor cells, but their role in these cells is still not clear. TLR3
      recognizes double-stranded RNA (poly (I:C)) and is primarily involved in the
      defense against viruses. TLR3 ligand binding initiates the activation of
      transcription factors NF-kappaB, IRF family members, and AP-1, which can induce
      wide cascading effect on the cell and consequently activate many cellular
      processes. Since little is known about TLR3 target genes, we have used the
      proteomic approach to widen the current knowledge. In this study, we have
      discovered 15 differentially expressed proteins, mostly connected with protein
      metabolic processes. Furthermore, we have confirmed by Western blot that
      calreticulin and profilin-1, proteins which have been shown previously to be
      involved in processes connected with tumor progression, are differentially
      expressed after poly(I:C) treatment. By using TLR3 small interfering RNA, we
      showed that calreticulin expression might be TLR3 dependent, unlike profilin-1.

PMID- 22415226
TI  - Circulating levels of endothelin-1 (ET-1) and its precursor (Big ET-1) in breast
      cancer early diagnosis.
AB  - Deregulation of the endothelin system, comprised of endothelin-1 (ET-1), its
      isoforms (ET-2 and ET-3) and their receptors (ET(A)R and ET(B)R), is under
      investigation in various types of human cancer. ET-1 has been suggested to
      participate in breast cancer development and progression, while Big ET-1, its
      biological precursor, has also been found elevated in breast cancer patients. In
      the present study, we investigated plasma ET-1 and Big ET-1 levels in patients
      with suspicious mammographic lesions, in order to assess their potential
      application as diagnostic biomarkers in the early estimation of breast disease.
      The study consisted of 94 patients (Group A to 30 patients with invasive ductal
      carcinoma: Group B, 30 with ductal carcinoma in situ; and group C, 34 with
      papilloma or ductal hyperplasia), who underwent an image-guided vacuum-assisted
      breast biopsy, and 30 healthy controls (group D). ET-1 and Big ET-1 plasma levels
      were measured with enzyme-linked immunosorbent assay. ET-1 levels did not exhibit
      significant differences between patients and healthy controls (Group A to 0.92
      fmol/mL; Group B: 0.90 fmol/mL; Group C: 0.66 fmol/mL; and Group D: 0.86
      fmol/mL). In contrast, Big ET-1 levels were significantly higher in patients with
      invasive or in situ carcinoma compared to healthy controls (Group A: 0.69
      fmol/mL; Group B, 0.62 fmol/mL; and group D: 0.39 fmol/mL; p < 0.001 and p <
      0.01). Plasma Big ET-1 may provide a useful tool for the early detection of
      invasive or noninvasive ductal breast cancer. The utilization of such a
      diagnostic tool would greatly assist in the modern management of breast cancer.

PMID- 22415227
TI  - Demoralization in mental health organizations: leadership and social support
      help.
AB  - Demoralization is a commonly observed feeling state that is characterized by a
      sense of loss of or threat to one's personal values or goals and a perceived
      inability to overcome obstacles toward achieving these goals. Demoralization has
      features in common with burnout and may precede or accompany it. Psychiatrists
      working in many mental health care organizational settings, be they in the public
      or private sectors, may be at particular risk for demoralization. This is due
      partly to stressors that threaten their own professional values because of
      factors such as programmatic cut backs, budgetary reductions and changing social
      emphases on the value of mental health treatments. They also may be at risk for
      demoralization because of the effects on them of the governance styles of the
      agencies in which they are employed. The leadership or governance style in large
      organizational settings often is authoritarian, hierarchical and bureaucratic,
      approaches that are antithetical to the more participative leadership styles
      favored by many mental health professionals in their clinical activities.
      Clinical leaders in mental health organizations must exhibit various competencies
      to successfully address demoralization in clinical staff and to provide a
      counterbalance to the effects of the governance style of many agencies in which
      they are employed. Appropriate leadership skills, sometimes too simplistically
      termed "social support", have been found to reduce burnout in various populations
      and are likely to lessen demoralization as well. This paper reviews these
      important leadership issues and the relationship of social support to recognized
      leadership competencies.

PMID- 22415228
TI  - Assigning kinetic 3D-signatures to glycocodes.
AB  - Reconciling glycocodes and their associated bioactivities, via 3D-structure, will
      rationalise burgeoning high-throughput functional glycomics data and underpin a
      new era of opportunity in chemical biology. A major impasse to achieving this
      goal is a detailed understanding of pyranose sugar ring 3D-conformation (or
      pucker) and the affiliated microsecond-timescale exchange kinetics. Here, we
      perform hardware-accelerated kinetically-rigorous equilibrium simulations of
      fundamental monosaccharides to produce the hypothesis that pyranoses have
      microsecond-timescale kinetic puckering signatures in water, classified as
      unstable (rare in the glycome), metastable (infrequently observed) and stable
      (prevalent). The predicted MUs-metastability of beta-d-glucose explained hitherto
      irreconcilable experimental measurements. Twisted puckers seen in carbohydrate
      enzymes were present in the aqueous 3D-ensemble (suggesting preorganization) and
      pyranose-water interactions accounted for the relative stability of beta-d
      galactose. Characteristic 3D-shapes for biologically- and commercially-important
      carbohydrates and new rules linking chemical modifications with pyranose MUs
      puckering kinetics are proposed. The observations advance structural-glycomics
      towards dynamic 3D-templates suitable for structure-based design.

PMID- 22415229
TI  - Loss of GPER identifies new targets for therapy among a subgroup of ERalpha
      positive endometrial cancer patients with poor outcome.
AB  - BACKGROUND: The G protein-coupled oestrogen receptor, GPER, has been suggested as
      an alternative oestrogen receptor. Our purpose was to investigate the potential
      of GPER as a prognostic and predictive marker in endometrial carcinoma and to
      search for new drug candidates to improve treatment of aggressive disease.
      MATERIALS AND METHOD: A total of 767 primary endometrial carcinomas derived from
      three patient series, including an external dataset, were studied for protein and
      mRNA expression levels to investigate and validate if GPER loss identifies poor
      prognosis and new targets for therapy in endometrial carcinoma. Gene expression
      levels, according to ERalpha/GPER status, were used to search the connectivity
      map database for small molecular inhibitors with potential for treatment of
      metastatic disease for receptor status subgroups. RESULTS: Loss of GPER protein
      is significantly correlated with low GPER mRNA, high FIGO stage, non-endometrioid
      histology, high grade, aneuploidy and ERalpha loss (all P-values <=0.05). Loss of
      GPER among ERalpha-positive patients identifies a subgroup with poor prognosis
      that until now has been unrecognised, with reduced 5-year survival from 93% to
      76% (P=0.003). Additional loss of GPER from primary to metastatic lesion
      counterparts further supports that loss of GPER is associated with disease
      progression. CONCLUSION: These results support that GPER status adds clinically
      relevant information to ERalpha status in endometrial carcinoma and suggest a
      potential for new inhibitors in the treatment of metastatic endometrial cancers
      with ERalpha expression and GPER loss.

PMID- 22415230
TI  - Magnesium intake, plasma C-peptide, and colorectal cancer incidence in US women:
      a 28-year follow-up study.
AB  - BACKGROUND: Laboratory studies suggest a possible role of magnesium intake in
      colorectal carcinogenesis but epidemiological evidence is inconclusive. METHOD:
      We tested magnesium-colorectal cancer hypothesis in the Nurses' Health Study, in
      which 85 924 women free of cancer in 1980 were followed until June 2008. Cox
      proportional hazards regression models were used to estimate multivariable
      relative risks (MV RRs, 95% confidence intervals). RESULTS: In the age-adjusted
      model, magnesium intake was significantly inversely associated with colorectal
      cancer risk; the RRs from lowest to highest decile of total magnesium intake were
      1.0 (ref), 0.93, 0.81, 0.72, 0.74, 0.77, 0.72, 0.75, 0.80, and 0.67
      (P(trend)<0.001). However, in the MV model adjusted for known dietary and non
      dietary risk factors for colorectal cancer, the association was significantly
      attenuated; the MV RRs were 1.0 (ref), 0.96, 0.85, 0.78, 0.82, 0.86, 0.84, 0.91,
      1.02, and 0.93 (P(trend)=0.77). Similarly, magnesium intakes were significantly
      inversely associated with concentrations of plasma C-peptide in age-adjusted
      model (P(trend)=0.002) but not in multivariate-adjusted model (P(trend)=0.61).
      Results did not differ by subsite or modified by calcium intakes or body mass
      index. CONCLUSION: These prospective results do not support an independent
      association of magnesium intake with either colorectal cancer risk or plasma C
      peptide levels in women.

PMID- 22415231
TI  - Major ethnic group differences in breast cancer screening uptake in Scotland are
      not extinguished by adjustment for indices of geographical residence, area
      deprivation, long-term illness and education.
AB  - BACKGROUND: Breast cancer screening data generally show lower uptake in minority
      ethnic groups. We investigated whether such variations occur in Scotland.
      METHODS: Using non-disclosive computerised linkage we combined Scottish breast
      screening and Census 2001 data. Non-attendance at first breast-screening
      invitation (2002-2008) was compared between 11 ethnic groups using age-adjusted
      risk ratios (RR) with 95% confidence intervals (CI), multiplied by 100, using
      Poisson regression. RESULTS: Compared with the White Scottish (RR=100), non
      attendance was similar for Other White British (99.5, 95% CI 96.1-103.2) and
      Chinese (112.8, 95% CI 96.3-132.2) and higher for Pakistani (181.7, 95% CI 164.9
      200.2), African (162.2, 95% CI 130.8-201.1), Other South Asian (151.7, 95% CI
      118.9-193.7) and Indian (141.7, 95% CI 121.1-165.7) groups. Adjustment for rural
      vs urban residence, long-term illness, area deprivation and education, associated
      with risk of non-attendance, increased the RR for non-attendance except for
      Pakistani women where it was modestly attenuated (RR=164.9, 149.4-182.1).
      CONCLUSION: Our data show important inequality in breast cancer screening uptake,
      not attenuated by potential confounding factors. Ethnic inequalities in breast
      screening attendance are of concern especially given evidence that the
      traditionally lower breast cancer rates in South Asian groups are converging
      towards the risks in the White UK population. Notwithstanding the forthcoming
      review of breast cancer screening, these data call for urgent action.

PMID- 22415232
TI  - Safety of UFT/LV and S-1 as adjuvant therapy for stage III colon cancer in phase
      III trial: ACTS-CC trial.
AB  - BACKGROUND: The Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC) is
      a phase III trial designed to validate the non-inferiority of S-1 to
      UFT/leucovorin (LV) as postoperative adjuvant chemotherapy for stage III colon
      cancer. We report the results of a planned safety analysis. METHODS: Patients
      aged 20-80 years with curatively resected stage III colon cancer were randomly
      assigned to receive UFT/LV (UFT, 300 mg m(-2) per day as tegafur; LV, 75 mg per
      day on days 1-28, every 35 days, 5 courses) or S-1 (80, 100, or 120 mg per day on
      days 1-28, every 42 days, 4 courses). Treatment status and safety were evaluated.
      RESULTS: Of 1535 enrolled patients, a total of 1504 (756 allocated to S-1 and 748
      to UFT/LV) were analysed. The completion rate of protocol treatment was 77% in
      the S-1 group and 73% in the UFT/LV group. The overall incidence of adverse
      events (AEs) were 80% in S-1 and 74% in UFT/LV. Stomatitis, anorexia,
      hyperpigmentation, and haematological toxicities were common in S-1, whereas
      increased alanine aminotransferase and aspartate aminotransferase were common in
      UFT/LV. The incidences of ?grade 3 AEs were 16% and 14%, respectively.
      CONCLUSION: Although AE profiles differed between the groups, feasibility of the
      protocol treatment was good. Both S-1 and UFT/LV could be safely used as adjuvant
      chemotherapy.

PMID- 22415233
TI  - The chemokine, CXCL12, is an independent predictor of poor survival in ovarian
      cancer.
AB  - BACKGROUND: The chemokine CXCL12 and its cognate receptor, CXCR4, have been
      implicated in numerous tumour types where expression promotes tumour growth,
      angiogenesis, metastasis and suppresses tumour immunity. METHODS: Using a tissue
      microarray of 289 primary ovarian cancers coupled to a comprehensive database of
      clinicopathological variables, the expression of CXCL12 and CXCR4 was assessed by
      immunohistochemistry and its impact in terms of survival and clinicopathological
      variables was determined. RESULTS: Patients whose tumours expressed high levels
      of CXCL12 had significantly poorer survival (P=0.026) than patients whose tumours
      failed to produce this chemokine. Lack of CXCL12 expression within tumours was
      associated with a 51-month survival advantage for patients when compared with
      patients whose tumours expressed high levels of CXCL12. FIGO stage, adjuvant
      chemotherapy and the absence of macroscopic disease after surgery were all shown
      to predict prognosis independently of each other in this cohort of patients.
      CXCL12 was independently predictive of prognosis on multivariate analysis
      (P=0.016). There was no correlation between CXCL12 and any clinicopathological
      variable. CONCLUSION: The chemokine CXCL12 is an independent predictor of poor
      survival in ovarian cancer. High expression of CXCL12 was seen in only 20% of the
      tumours, suggesting a role for anti-CXCL12/CXCR4 therapy in the management of
      these patients.

PMID- 22415234
TI  - Impact of genomic stability on protein expression in endometrioid endometrial
      cancer.
AB  - BACKGROUND: Genomic stability is one of the crucial prognostic factors for
      patients with endometrioid endometrial cancer (EEC). The impact of genomic
      stability on the tumour tissue proteome of EEC is not yet well established.
      METHODS: Tissue lysates of EEC, squamous cervical cancer (SCC), normal
      endometrium and squamous cervical epithelium were subjected to two-dimensional
      (2D) gel electrophoresis and identification of proteins by MALDI TOF MS.
      Expression of selected proteins was analysed in independent samples by
      immunohistochemistry. RESULTS: Diploid and aneuploid genomically unstable EEC
      displayed similar patterns of protein expression. This was in contrast to diploid
      stable EEC, which displayed a protein expression profile similar to normal
      endometrium. Approximately 10% of the differentially expressed proteins in EEC
      were specific for this type of cancer with differential expression of other
      proteins observed in other types of malignancy (e.g., SCC). Selected proteins
      differentially expressed in 2D gels of EEC were further analysed in an EEC
      precursor lesion, that is, atypical hyperplasia of endometrium, and showed
      increased expression of CLIC1, EIF4A1 and PRDX6 and decreased expression of ENO1,
      ANXA4, EMD and Ku70. CONCLUSION: Protein expression in diploid and aneuploid
      genomically unstable EEC is different from the expression profile of proteins in
      diploid genomically stable EEC. We showed that changes in expression of proteins
      typical for EEC could already be detected in precursor lesions, that is, atypical
      hyperplasia of endometrium, highlighting their clinical potential for improving
      early diagnostics of EEC.

PMID- 22415235
TI  - Mutation analysis of RAD51D in non-BRCA1/2 ovarian and breast cancer families.
AB  - BACKGROUND: Recent data show that mutations in RAD51D have an aetiological role
      in ovarian carcinoma, yet mutations do not appear to be associated with an
      increased risk for breast cancer. We studied ovarian and breast cancer families
      having at least one woman affected by ovarian carcinoma, to assess the importance
      of RAD51D mutations in such families. METHODS: The coding region of the RAD51D
      gene was analysed in 175 BRCA1/2-negative families with family histories of both
      ovarian and breast cancer ascertained from two Canadian and two Belgian
      institutions. RESULTS: We identified one previously reported deleterious
      mutation, p.Arg186(*) (c.556C>T), and two novel variants; missense substitution
      p.Cys119Arg and an intronic variant c.83-26A>G. p.Arg186(*) segregated with the
      disease in the family and two ovarian carcinomas available for analysis showed
      loss of the wild-type allele, but the novel variants are likely neutral.
      CONCLUSION: RAD51D should be included in genetic screening of ovarian cancer
      families that do not have BRCA1/BRCA2 mutations. We show that mutations are more
      likely to be found in families with two or more ovarian cancers, or in probands
      with first-degree relatives with ovarian cancer, and we feel testing should be
      preferentially offered to affected women from such families.

PMID- 22415237
TI  - How many strata in an RCT? A flexible approach.
AB  - BACKGROUND: The need to allow for prognostic factors when designing and analysing
      cancer trials is well recognised, but the possibility of overstratification
      should be avoided by restricting the number of strata. The proposed method
      improves on existing guidance by being based on explicit principles and being
      more adaptable to circumstances, and should be of particular use to clinicians
      when designing a trial. METHODS: Given a proposed sample size, a minimum
      allowable number in a stratum and an acceptable risk of observing fewer than this
      minimum, the number of strata can then be obtained by assuming a Poisson
      distribution for the number of observations per stratum. This can easily be
      programmed into Excel. RESULTS: An example is given for a hypothetical typical
      trial of 250 patients, which for 80% power and 5% two-sided significance would
      correspond to a Cohen's effect size of 0.355 (about halfway between the 'small'
      and 'moderate' thresholds). To have a <1% risk of fewer than 10 patients in a
      stratum, no >13 strata should be considered. For a survival analysis with the
      same overall sample size but 170 deaths, no >9 strata would be prudent. In the
      context of a cancer trial this could easily be met by only two prognostic
      variables. CONCLUSION: The method proposed is flexible and based on explicit
      principles and may be applied in the design or analysis of both clinical trials
      and epidemiological studies.

PMID- 22415236
TI  - The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR
      inhibition.
AB  - BACKGROUND: Combined targeting of MAPK and PI3K signalling pathways may be
      necessary for optimal therapeutic activity in cancer. This study evaluated the
      MEK inhibitors AZD6244 and PD0325901, alone and in combination with the dual
      mTOR/PI3K inhibitor NVP-BEZ235 or the PI3K inhibitor GDC-0941, in three
      colorectal cancer cell lines. METHODS: Growth inhibition, survival and signal
      transduction were measured using the Sulforhodamine B assay, clonogenicity and
      western blotting, respectively, in HCT116, HT29 and DLD1 cell lines. RESULTS: All
      MEK/PI3K inhibitor combinations exhibited marked synergistic growth inhibition;
      however, GDC-0941 displayed greater synergy in combination with either MEK
      inhibitor. NVP-BEZ235 exhibited stronger inhibition of 4EBP1 phosphorylation, and
      similar inhibition of S6 and AKT phosphorylation, compared with GDC-0941. Both
      PD0325901 and AZD6244 inhibited ERK phosphorylation, and with MEK/PI3K inhibitor
      combinations inhibition of S6 phosphorylation was increased. The reduced synergy
      exhibited by NVP-BEZ235 in combination with MEK inhibitors, compared with GDC
      0941, may be due to inhibition of mTOR, and the addition of the mTORC1/2
      inhibitor KU0063794 compromised the synergy of GDC-0941:PD0325901 combinations.
      CONCLUSION: These studies confirm that dual targeting of PI3K and MEK can induce
      synergistic growth inhibition; however, the combination of specific PI3K
      inhibitors, rather than dual mTOR/PI3K inhibitors, with MEK inhibitors results in
      greater synergy.

PMID- 22415238
TI  - Detection of Merkel cell virus and correlation with histologic presence of Merkel
      cell carcinoma in sentinel lymph nodes.
AB  - BACKGROUND: Adjuvant treatment can dramatically improve the survival of patients
      with metastatic Merkel cell carcinoma (MCC), making early, accurate detection of
      nodal disease critical. The purpose of this study was to correlate Merkel cell
      virus (MCV) detection with histopathologic disease in sentinel lymph nodes (SLNs)
      of MCC. METHODS: Merkel cell carcinoma cases with SLN (n=25) were compared with
      negative controls (n=27). Viral load was obtained by quantitative polymerase
      chain reaction (PCR) for regions VP1 and LT3 of MCV. Histopathologic disease and
      viral load were correlated. RESULTS: Merkel cell virus was detected in 16 out of
      17 (94%) of primary MCC (mean viral load (MVL)=1.44 copies per genome). Viral
      load in the negative controls was <0.01 copies per genome. Merkel cell carcinoma
      was present in 5 out of 25 (20%) SLN by histopathology, and MCV was detected in
      11 out of 25 (44%) MCC SLN (MVL=1.68 copies per genome). In all, 15 out of 25
      (60%) SLN showed correlation between histologic and MCV results. In all, 2 out of
      25 (8%) samples were histopathologically positive and PCR negative. Of note, 8
      out of 25 (32%) samples had detectable MCV without microscopic disease.
      CONCLUSION: Patients with positive SLN for MCV even if negative by histopathology
      were identified. The application of molecular techniques to detect subhistologic
      disease in SLN of MCC patients may identify a subset of patients who would
      benefit from adjuvant nodal treatment.

PMID- 22415239
TI  - The Aarhus statement: improving design and reporting of studies on early cancer
      diagnosis.
AB  - Early diagnosis is a key factor in improving the outcomes of cancer patients. A
      greater understanding of the pre-diagnostic patient pathways is vital yet, at
      present, research in this field lacks consistent definitions and methods. As a
      consequence much early diagnosis research is difficult to interpret. A consensus
      group was formed with the aim of producing guidance and a checklist for early
      cancer-diagnosis researchers. A consensus conference approach combined with
      nominal group techniques was used. The work was supported by a systematic review
      of early diagnosis literature, focussing on existing instruments used to measure
      time points and intervals in early cancer-diagnosis research. A series of
      recommendations for definitions and methodological approaches is presented. This
      is complemented by a checklist that early diagnosis researchers can use when
      designing and conducting studies in this field. The Aarhus checklist is a
      resource for early cancer-diagnosis research that should promote greater
      precision and transparency in both definitions and methods. Further work will
      examine whether the checklist can be readily adopted by researchers, and feedback
      on the guidance will be used in future updates.

PMID- 22415241
TI  - Metronomic chemotherapy with cyclophosphamide and dexamethasone in patients with
      metastatic carcinoma of the prostate.

PMID- 22415242
TI  - External mouthpart morphology in the Tenuipalpidae (Tetranychoidea): Raoiella a
      case study.
AB  - The use of low-temperature scanning electron microscopy (LTSEM) to study external
      mouthpart morphology in the Tenuipalpidae, in particular the genus Raoiella, has
      brought some aspects of the mechanics of feeding in this group into question. In
      addition, an LTSEM study on the specialized feeding behaviour of Raoiella indica
      Hirst (Tetranychoidea: Tenuipalpidae) revealed host plant use in this species
      could be affected by stomatal complex morphology.

PMID- 22415243
TI  - Underwater survival of Rhipicephalus sanguineus (Acari: Ixodidae).
AB  - Rhipicephalus sanguineus (Acari: Ixodidae) is a worldwide distributed tick, also
      due to its adaptability to different environmental conditions. In order to assess
      its ability to survive and to lay eggs after water immersion, 150 engorged
      females from southern Italy were water immersed for 1-15 days whereas eggs were
      flooded for 1-5 days. All females survived water immersion for 48 h, some of them
      up to 72 h, but egg hatch rate was negatively correlated with female submersion
      period. All eggs flooded for up to 120 h hatched successfully. These findings
      suggest that R. sanguineus is able to survive underwater for some days without
      loosing any biological activity. This feature should be considered in relation to
      its potential to spread to new areas and to its role as a vector of pathogens
      also in consideration of changes in climate the Earth is currently experiencing.

PMID- 22415244
TI  - Acaricidal activity and repellency of essential oil from Piper aduncum and its
      components against Tetranychus urticae.
AB  - The chemical composition of essential oil of leaves of Piper aduncum L., growing
      wild in a fragment of the Atlantic Rainforest biome in northeastern Brazil, was
      determined through gas chromatography-mass spectrometry. The acaricidal activity
      and repellency of the essential oil and its components [dillapiole (0.28 g/ml),
      alpha-humulene (0.016 g/ml), (E)-nerolidol (0.0007 g/ml) and beta-caryophyllene
      (0.0021 g/ml)] were evaluated in the laboratory against adults of Tetranychus
      urticae Koch. The mites were more susceptible to the oil in fumigation tests
      (LC(50) = 0.01 MUl/l of air) than in contact test with closed Petri dish (LC(50)
      = 7.17 MUl/ml); mortality was reduced by approximately 50 % in the latter test.
      The repellent action of the oil and toxicity by fumigation and contact did not
      differ significantly from the positive control (eugenol). The repellent activity
      was attributed to the components (E)-nerolidol, alpha-humulene and beta
      caryophyllene, whereas toxicity by fumigation and contact was attributed to beta
      caryophyllene. The effect of Piper oil and the role of its components regarding
      host plant preference with a two-choice leaf disk test are also discussed.

PMID- 22415245
TI  - On the structure and dynamics of the hydrated sulfite ion in aqueous solution--an
      ab initio QMCF MD simulation and large angle X-ray scattering study.
AB  - Theoretical ab initio quantum mechanical charge field molecular dynamics (QMCF
      MD) formalism has been applied in conjunction to experimental large angle X-ray
      scattering to study the structure and dynamics of the hydrated sulfite ion in
      aqueous solution. The results show that there is a considerable effect of the
      lone electron-pair on sulfur concerning structure and dynamics in comparison with
      the sulfate ion with higher oxidation number and symmetry of the hydration shell.
      The S-O bond distance in the hydrated sulfite ion has been determined to 1.53(1)
      A by both methods. The hydrogen bonds between the three water molecules bound to
      each sulfite oxygen are only slightly stronger than those in bulk water. The
      sulfite ion can therefore be regarded as a weak structure maker. The water
      exchange rate is somewhat slower for the sulfite ion than for the sulfate ion,
      tau(0.5) = 3.2 and 2.6 ps, respectively. An even more striking observation in the
      angular radial distribution (ARD) functions is that the for sulfite ion the water
      exchange takes place in close vicinity of the lone electron-pair directed at its
      sides, while in principle no water exchange did take place of the water molecules
      hydrogen bound to sulfite oxygens during the simulation time. This is also
      confirmed when detailed pathway analysis is conducted. The simulation showed that
      the water molecules hydrogen bound to the sulfite oxygens can move inside the
      hydration shell to the area outside the lone electron-pair and there be
      exchanged. On the other hand, for the hydrated sulfate ion in aqueous solution
      one can clearly see from the ARD that the distribution of exchange events is
      symmetrical around the entire hydration sphere.

PMID- 22415246
TI  - Methods for comprehensive chromosome screening of oocytes and embryos:
      capabilities, limitations, and evidence of validity.
AB  - Preimplantation aneuploidy screening of cleavage stage embryos using fluorescence
      in situ hybridization (FISH) may no longer be considered the standard of care in
      reproductive medicine. Over the last few years, there has been considerable
      development of novel technologies for comprehensive chromosome screening (CCS) of
      the human genome. Among the notable methodologies that have been incorporated are
      whole genome amplification, metaphase and array based comparative genomic
      hybridization, single nucleotide polymorphism microarrays, and quantitative real
      time PCR. As these methods become more integral to treating patients with
      infertility, it is critical that clinicians and scientists obtain a better
      understanding of their capabilities and limitations. This article will focus on
      reviewing these technologies and the evidence of their validity.

PMID- 22415247
TI  - Genetic screening for chromosomal abnormalities and Y chromosome microdeletions
      in Chinese infertile men.
AB  - PURPOSES: To investigate the frequency and type of both chromosomal abnormalities
      and Y chromosome microdeletions and analyze their association with defective
      spermatogenesis in Chinese infertile men. METHODS: This is a single center study.
      Karyotyping using G-banding and screening for Y chromosome microdeletion by
      multiplex polymerase chain reaction(PCR)were performed in 200 controls and 1,333
      infertile men, including 945 patients with non-obstructive azoospermia and 388
      patients with severe oligozoospermia. RESULTS: Out of 1,333 infertile patients,
      154(11.55%) presented chromosomal abnormalities. Of these, 139 of 945 (14.71%)
      were from the azoospermic and 15 of 388 (3.87%) from the severe oligozoospermic
      patient groups. The incidence of sex chromosomal abnormalities in men with
      azoospermia was 11.53% compared with 1.03% in men with severe oligozoospermia (P
      < 0.01). Also 144 of 1,333(10.80%) patients presented Y chromosome
      microdeletions. The incidence of azoospermia factor(AZF) microdeletion was 11.75%
      and 8.51% in patients with azoospermia and severe oligozoospermia respectively.
      Deletion of AZFc was the most common and deletions in AZFa or AZFab or AZFabc
      were found in azoospermic men. In addition, 34 patients had chromosomal
      abnormalities among the 144 patients with Y chromosome microdeletions. No
      chromosomal abnormality and microdeletion in AZF region were detected in
      controls. CONCLUSIONS: There was a high incidence (19.80%) of chromosomal
      abnormalities and Y chromosomal microdeletions in Chinese infertile males with
      azoospermia or severe oligozoospermia. These findings strongly suggest that
      genetic screening should be advised to infertile men before starting assisted
      reproductive treatments.

PMID- 22415248
TI  - Paediatric adverse drug reactions reported to the Spanish Pharmacovigilance
      System from 2004 to 2009.
AB  - PURPOSE: This study was conducted to evaluate relevant new information about ADRs
      reported in the Spanish paediatric population over a 6-year period. METHODS:
      Adverse drug reactions (ADRs) for individuals aged 0-17 years reported to the
      Spanish Pharmacovigilance System from 2004 to 2009 were analysed with respect to
      time, age and sex, category of ADR [System Organ Class (SOC)], seriousness,
      suspected medicines [level 2 of the Anatomical Therapeutic Chemical (ATC)
      Classification System] and type of reporter. RESULTS: In total, 4,279 ADR reports
      corresponding to 8,196 ADRs were analysed, approximately two ADRs per report. The
      rate of paediatric ADR reports in 2009 was 165 per million, of which nearly half
      (46 %) were for children (age group 2-11 years). Similar total numbers of ADRs
      were reported for boys and girls. The most frequent ADRs reported were from the
      following SOCs: general disorders and administration site conditions (34 %); skin
      and subcutaneous tissue disorders (15 %); nervous system disorders (14 %).
      Reports encompassed medicines from various ATC groups: vaccines and anti
      infectives for systemic use (67 %); nervous system (9 %); respiratory system (9
      %). On average, 37 % of ADRs were classified as serious. There were 33 fatal
      ADRs, and 35 % of the paediatric population associated with the ADR notifications
      required hospitalization or extended hospital stay. CONCLUSIONS: In Spain, ADR
      reporting rate in the paediatric population has increased since 2004. The
      proportion of suspected ADR reports related to vaccines was predominant, which
      highlights the important role played by nurses. ADR notification of congenital
      malformations in newborn infants highlights the need for joint action between the
      Spanish System of Pharmacovigilance of Medicines for Human Use (SEFV-H) and
      paediatricians, obstetricians and gynaecologists. The publication of safety
      reports by regulatory agencies is determinant for the increased number of ADR
      notifications.

PMID- 22415249
TI  - On the definition and the computation of the type-reproduction number T for
      structured populations in heterogeneous environments.
AB  - In the context of mathematical epidemiology, the type-reproduction number (TRN)
      for a specific host type is interpreted as the average number of secondary cases
      of that type produced by the primary cases of the same host type during the
      entire course of infection. Here, it must be noted that T takes into account not
      only the secondary cases directly transmitted from the specific host but also the
      cases indirectly transmitted by way of other types, who were infected from the
      primary cases of the specific host with no intermediate cases of the target host.
      Roberts and Heesterbeek (Proc R Soc Lond B 270:1359-1364, 2003) have shown that T
      is a useful measure when a particular single host type is targeted in the disease
      control effort in a community with various types of host, based on the fact that
      the sign relation sign(R0-1) = sign(T-1) holds between the basic reproduction
      number R0 and T. In fact, T can be seen as an extension of R0 in a sense that the
      threshold condition of the total population growth can be formulated by the
      reproduction process of the target type only. However, the original formulation
      is limited to populations with discrete state space in constant environments. In
      this paper, based on a new perspective of R0 in heterogeneous environments (Inaba
      in J Math Biol 2011), we give a general definition of the TRN for continuously
      structured populations in heterogeneous environments and show some examples of
      its computation and applications.

PMID- 22415251
TI  - Risks of endemicity, morbidity and perspectives regarding the control of Chagas
      disease in the Amazon Region.
AB  - Chagas disease, in the Amazon Region as elsewhere, can be considered an enzootic
      disease of wild animals or an anthropozoonosis, an accidental disease of humans
      that is acquired when humans penetrate a wild ecosystem or when wild triatomines
      invade human dwellings attracted by light or searching for human blood. The risk
      of endemic Chagas disease in the Amazon Region is associated with the following
      phenomena: (i) extensive deforestation associated with the displacement of wild
      mammals, which are the normal sources of blood for triatomines, (ii) adaptation
      of wild triatomines to human dwellings due to the need for a new source of blood
      for feeding and (iii) uncontrolled migration of human populations and domestic
      animals that are already infected with Trypanosoma cruzi from areas endemic for
      Chagas disease to the Amazon Region. Several outbreaks of severe acute cases of
      Chagas disease, as well as chronic cases, have been described in the Amazon
      Region. Control measures targeted to avoiding endemic Chagas disease in the
      Amazon Region should be the following: improving health education in communities,
      training public health officials and communities for vector and Chagas disease
      surveillance and training local physicians to recognise and treat acute and
      chronic cases of Chagas diseases as soon as possible.

PMID- 22415250
TI  - Complexity and dynamics of host-fungal interactions.
AB  - Pathologies attributable to fungal infections represent a growing concern in both
      developed and developing countries. Initially discovered as opportunistic
      pathogens of immunocompromised hosts, fungi such as Candida albicans are now
      being placed at the centre of a more complex and dynamic picture in which the
      outcome of an infection is the result of an intricate network of molecular
      interactions between the fungus, the host and the commensal microflora co
      inhabiting various host niches, and especially the gastrointestinal (GI) tract.
      The complexity of the host-fungal interaction begins with the numerous pathogen
      associated molecular patterns (PAMPs) present on the fungal cell wall that are
      recognized by multiple pathogen-recognition receptors (PRRs), expressed by
      several types of host cells. PAMP-PRR interactions elicit a variety of
      intracellular signalling pathways leading to a wide array of immune responses,
      some of which promote fungal clearance while others contribute to pathogenesis.
      The picture is further complicated by the fact that numerous commensal bacteria
      normally co-inhabiting the host's GI tract produce molecules that either directly
      modulate the survival and virulence of commensal fungi such as C. albicans or
      indirectly modulate the host's antifungal immune responses. On top of this
      complexity, this host-microbiome-fungal interaction exhibits features of a
      dynamic system, in which the same fungi can easily switch between different
      morphological forms presenting different PAMPs at different moments of time.
      Furthermore, fungal pathogens can rapidly accumulate genomic alterations that
      further modify their recognition by the immune system, their virulence and their
      resistance to antifungal compounds. Thus, based on available molecular data
      alone, it is currently difficult to construct a coherent model able to explain
      the balance between commensalism and virulence and to predict the outcome of a
      fungal infection. Here, we review current advances in our understanding of this
      complex and dynamic system and propose new avenues of investigation to assemble a
      more complete picture of the host-fungal interaction, integrating microbiological
      and immunological data under the lens of systems biology and evolutionary
      genomics.

PMID- 22415252
TI  - Depletion of CD25+ cells during acute toxoplasmosis does not significantly
      increase mortality in Swiss OF1 mice.
AB  - The interleukin (IL)-2R alpha chain (CD25) is expressed on regulatory T cells
      (Treg), which constitute more than 85% of the CD25+ T cell population in a naive
      mouse. CD25 is also expressed on effector T cells in mice suffering from an acute
      infection by the obligate intracellular protozoan parasite, Toxoplasma gondii.
      Lethal toxoplasmosis is accompanied by a significant loss of Treg in mice
      naturally susceptible to toxoplasmosis. The present study was done to explore the
      role of Treg cells using an anti-CD25 antibody-mediated depletion in mice
      naturally resistant to toxoplasmosis. Although a significant decrease in the
      percentage of Treg cells was observed following anti-CD25 monoclonal antibody
      injections, the depletion of CD25+ cells during acute toxoplasmosis did not
      significantly increase the mortality of Swiss OF1 mice and no significant
      difference was observed in the brain parasitic load between the mice in the
      depleted-infected and isotype-infected groups. We found no significant difference
      between the titres of total IgG in the sera of the mice from the two groups in
      the chronic phase. However, CD25+ cells depletion was followed by significantly
      higher levels of IL-12 in the serum of depleted mice than in that of mice
      injected with the isotype control antibody.

PMID- 22415253
TI  - The distribution pattern of Lutzomyia longipalpis (Diptera: Psychodidae) in the
      peridomiciles of a sector with canine and human visceral leishmaniasis
      transmission in the municipality of Dracena, Sao Paulo, Brazil.
AB  - The specimen distribution pattern of a species can be used to characterise a
      population of interest and also provides area-specific guidance for pest
      management and control. In the municipality of Dracena, in the state of Sao
      Paulo, we analysed 5,889 Lutzomyia longipalpis specimens collected from the
      peridomiciles of 14 houses in a sector where American visceral leishmaniasis
      (AVL) is transmitted to humans and dogs. The goal was to analyse the dispersion
      and a theoretical fitting of the species occurrence probability. From January
      December 2005, samples were collected once per week using CDC light traps that
      operated for 12-h periods. Each collection was considered a sub-sample and was
      evaluated monthly. The standardised Morisita index was used as a measure of
      dispersion. Adherence tests were performed for the log-series distribution. The
      number of traps was used to adjust the octave plots. The quantity of Lu.
      longipalpis in the sector was highly aggregated for each month of the year,
      adhering to a log-series distribution for 11 of the 12 months analysed. A sex
      stratified analysis demonstrated a pattern of aggregated dispersion adjusted for
      each month of the year. The classes and frequencies of the traps in octaves can
      be employed as indicators for entomological surveillance and AVL control.

PMID- 22415254
TI  - Analysis of the NTPDase and ecto-5'-nucleotidase profiles in serum-limited
      Trichomonas vaginalis.
AB  - Trichomonas vaginalis is a parasite of the human urogenital tract that causes
      trichomonosis, the most prevalent non-viral sexually transmitted disease.
      Ectonucleoside triphosphate diphosphohydrolase (NTPDase) family members, which
      hydrolyse extracellular ATP and ADP and ecto-5'-nucleotidase, which hydrolyses
      AMP, have been characterised in T. vaginalis. For trichomonad culture, the growth
      medium is supplemented with 10% serum, which is an important source of nutrients,
      such as adenosine. Here, we investigated the ATP metabolism of T. vaginalis
      trophozoites from long-term cultures and clinical isolates under limited bovine
      serum conditions (1% serum). The specific enzymatic activities were expressed as
      nmol inorganic phosphate (Pi) released/min/mg protein, the gene expression
      patterns were determined by reverse transcriptase-polymerase chain reaction, the
      extracellular adenine nucleotide hydrolysis was analysed by high performance
      liquid chromatography and the cell cycle analysis was assessed by flow cytometry.
      Serum limitation led to the profound activation of NTPDase and ecto-5'
      nucleotidase activities. Furthermore, the levels of NTPDase A and B transcripts
      increased and extracellular ATP metabolism was activated, which led to enhanced
      ATP hydrolysis and the formation of ADP and AMP. Moreover, the cell cycle was
      arrested at the G0/G1 stage, which suggested adenosine uptake. Our data suggest
      that under conditions of serum limitation, NTPDase and ecto-5'-nucleotidase play
      a role in providing the adenosine required for T. vaginalis growth and that this
      process contributes to the establishment of parasitism.

PMID- 22415255
TI  - The phylogeny of Simulium (Chirostilbia) (Diptera: Simuliidae) and perspectives
      on the systematics of the genus in the Neotropical Region.
AB  - Recently, knowledge of Neotropical Simuliidae has been accumulating quickly.
      However, information about supra-specific relationships is scarce and diagnoses
      of Simulium subgenera are unsatisfactory. To investigate the relationships among
      Simulium (Chirostilbia) species and test the subgenus monophyly, we performed a
      cladistic analysis. The ingroup included all species of this subgenus and the
      outgroup included representatives of the 17 species groups of Neotropical
      Simulium and three Holarctic species. The study was based on a data matrix with
      31 terminal taxa and 45 morphological characteristics of adult, pupa and larva.
      The phylogenetic analysis under equal weights resulted in eight most-parsimonious
      trees (length = 178, consistency index = 34, retention index = 67). The monophyly
      of the S. (Chirostilbia) was not supported in our analysis. The Simulium
      subpallidum species group was closer to Simulium (Psilopelmia) and Simulium
      (Ectemnaspis) than to the Simulium pertinax species group. Additionally, we
      describe the three-dimensional shape of the terminalia of male and female of
      Simulium (Chirostilbia) for the first time and provide comments about the
      taxonomic problems involving some species of the subgenus: Simulium acarayense,
      Simulium papaveroi, S. pertinax, Simulium serranum, Simulium striginotum and S.
      subpallidum.

PMID- 22415256
TI  - Genetic and morphological characterisation of a new species of the genus
      Hysterothylacium (Nematoda) from Paralichthys isosceles Jordan, 1890 (Pisces:
      Teleostei) of the Neotropical Region, state of Rio de Janeiro, Brazil.
AB  - Taking into account the difficulties of taxonomic identification of larval
      anisakid nematodes based on morphological characters, genetic analyses were
      performed, together with those usually applied, in order to identify anisakid
      larvae found in the flounder Paralichthys isosceles from the littoral of the
      state of Rio de Janeiro, Brazil. The analysis of 1,820 larvae revealed a new
      species, similar to Hysterothylacium MD, Hysterothylacium 2, Hysterothylacium KB
      and Hysterothylacium sp regarding the absence of the larval tooth, an excretory
      pore situated below the nerve ring level, and slender lateral alae. Moreover, the
      new species differs from Hysterothylacium fortalezae and Hysterothylacium
      reliquens with regard to the number and size of spines present on the tail end
      and from Hysterothylacium patagonicus by the absence of interlabia. The maximum
      parsimony and neighbour joining tree topologies based on the 18S ribosomal DNA
      gene, complete internal transcribed spacer region and cytochrome oxidase 2 (COII)
      gene demonstrated that the Brazilian larvae belong to Raphidascarididae and
      represent a unique genetic entity, confirmed as a new Hysterothylacium species.
      Furthermore, the new species presents COII genetic signatures and shares
      polymorphisms with Raphidascarididae members. This is the first description of a
      new anisakid species from Brazil through the integration of morphological and
      molecular taxonomy data.

PMID- 22415257
TI  - An evaluation of the dot-ELISA procedure as a diagnostic test in an area with a
      high prevalence of human Toxocara canis infection.
AB  - The aim of this work was to evaluate a dot-enzyme-linked immunosorbent assay (dot
      ELISA) using excretory-secretory antigens from the larval stages of Toxocara
      canis for the diagnosis of toxocariasis. A secondary aim was to establish the
      optimal conditions for its use in an area with a high prevalence of human T.
      canis infection. The dot-ELISA test was standardised using different
      concentrations of the antigen fixed on nitrocellulose paper strips and increasing
      dilutions of the serum and conjugate. Both the dot-ELISA and standard ELISA
      methods were tested in parallel with the same batch of sera from controls and
      from individuals living in the problem area. The best results were obtained with
      1.33 ug/mL of antigen, dilutions of 1/80 for the samples and controls and a
      dilution of 1/5,000 for the anti-human IgG-peroxidase conjugate. All steps of the
      procedure were performed at room temperature. The coincidence between ELISA and
      dot-ELISA was 85% and the kappa index was 0.72. The dot-ELISA test described here
      is rapid, easy to perform and does not require expensive equipment. Thus, this
      test is suitable for the serological diagnosis of human T. canis infection in
      field surveys and in the primary health care centres of endemic regions.

PMID- 22415258
TI  - The persistence of multifocal colonisation by a single ABC genotype of Candida
      albicans may predict the transition from commensalism to infection.
AB  - Candida albicans is a common member of the human microbiota and may cause
      invasive disease in susceptible populations. Several risk factors have been
      proposed for candidaemia acquisition. Previous Candida multifocal colonisation
      among hospitalised patients may be crucial for the successful establishment of
      candidaemia. Nevertheless, it is still not clear whether the persistence or
      replacement of a single clone of C. albicans in multiple anatomical sites of the
      organism may represent an additional risk for candidaemia acquisition. Therefore,
      we prospectively evaluated the dynamics of the colonising strains of C. albicans
      for two groups of seven critically ill patients: group I included patients
      colonised by C. albicans in multiple sites who did not develop candidaemia and
      group II included patients who were colonised and who developed candidaemia. ABC
      and microsatellite genotyping of 51 strains of C. albicans revealed that patients
      who did not develop candidaemia were multiply colonised by at least two ABC
      genotypes of C. albicans, whereas candidaemic patients had highly related
      microsatellites and the same ABC genotype in colonising and bloodstream isolates
      that were probably present in different body sites before the onset of
      candidaemia.

PMID- 22415259
TI  - Co-infections associated with human immunodeficiency virus type 1 in pregnant
      women from southern Brazil: high rate of intraepithelial cervical lesions.
AB  - Human immunodeficiency virus type 1 (HIV-positive) pregnant women require
      specific prophylactic and therapeutic approaches. The efficacy of established
      approaches is further challenged by co-infection with other sexually transmitted
      diseases (STDs). The objective of this study was to determine the prevalence of
      co-infections in pregnant women infected with different HIV-1 subtypes and to
      relate these findings, together with additional demographic and clinical
      parameters, to maternal and infant outcomes. Blood samples from pregnant women
      were collected and tested for syphilis, hepatitis B virus (HBV) and hepatitis C
      virus (HCV). Human papillomavirus (HPV) diagnosis was evaluated by the presence
      of alterations in the cervical epithelium detected through a cytopathological
      exam. Medical charts provided patient data for the mothers and children.
      Statistical analyses were conducted with STATA 9.0. We found a prevalence of
      10.8% for HCV, 2.3% for chronic HBV, 3.1% for syphilis and 40.8% for HPV. Of
      those co-infected with HPV, 52.9% presented high-grade intraepithelial lesions or
      in situ carcinoma. Prematurity, birth weight, Apgar 1' and 5' and Capurro scores
      were similar between co-infected and non-co-infected women. The presence of other
      STDs did not impact maternal and concept outcomes. More than half of the patients
      presenting cervical cytology abnormalities suggestive of HPV had high-grade
      squamous intraepithelial lesions or cervical cancer, evidencing an alarming rate
      of these lesions.

PMID- 22415260
TI  - Acute experimental Trypanosoma cruzi infection: establishing a murine model that
      utilises non-invasive measurements of disease parameters.
AB  - Trypanosoma cruzi infection has a large public health impact in Latin American
      countries. Although the transmission rates via blood transfusions and insect
      vectors have declined sharply in the past 20 years due to policies of the
      Southern Cone countries, a large number of people are still at risk for
      infection. Currently, no accepted experimental model or descriptions of the
      clinical signs that occur during the course of acute murine infection are
      available. The aim of this work was to use non-invasive methods to evaluate the
      clinical signs of Balb/c mice infected with the Y strain of T. cruzi. The
      infected mice displayed evident clinical changes beginning in the third week of
      infection. The mice were evaluated based on physical characteristics, spontaneous
      activity, exploratory behaviour and physiological alterations. We hope that the
      results presented in this report provide parameters that complement the effective
      monitoring of trypanocidal treatment and other interventions used to treat
      experimental Chagas disease.

PMID- 22415261
TI  - Assessment of the treatment of chronic hepatitis C in the state of Mato Grosso,
      central Brazil.
AB  - In Brazil, the treatment of hepatitis C virus (HCV) infection is funded by the
      national public health system (SUS). To evaluate treatment results in the state
      of Mato Grosso, central Brazil, we have consulted the files of the office of the
      State Department of Health responsible for supplying such medications. We
      obtained information on 232 treatments of 201 patients who underwent treatment in
      or prior to 2008. The study was conducted by reviewing medical records, making
      telephone calls and interviewing the assistant physicians. Thirty-nine patients
      (19.4%) had cirrhosis and HCV genotype 1 predominated (64.3%). Excluding patients
      with comorbidities or treatment without ribavirin we analysed 175 treatments
      (sustained virologic response occurred in 32.6% of cases). Twenty-six of these
      175 were retreatments and the sustained virological response (SVR) rate among
      them was 30.8%; the SVR rate was 32.9% among those receiving treatment for the
      first time. The SVR rate of genotype 1 patients was 27.8%, whereas it was 37.5%
      in non-1 genotype patients. The adjusted multivariate analysis showed association
      of SVR with the absence of cirrhosis [odds ratio (OR): 7.7; confidence interval
      (CI) 95%: 2.5, 33.3], the use of pegylated interferon (OR: 5.8; CI 95%: 1.5,
      21.4), non-1 genotype (OR: 5.3; CI 95%: 1.7, 16.7) and uninterrupted treatment
      (OR: 9.0; CI 95%: 3.3, 45.4). The SVR rates were similar to those found in other
      Brazilian studies about HCV, but lower than those found in national and
      international clinical trials. These data suggest that the treatments of chronic
      hepatitis C that are made available by SUS does not, under normal conditions,
      work as well as the original controlled studies indicated.

PMID- 22415262
TI  - HLA-A*01 allele: a risk factor for dengue haemorrhagic fever in Brazil's
      population.
AB  - Severe forms of dengue, such as dengue haemorrhagic fever (DHF) and dengue shock
      syndrome, are examples of a complex pathogenic mechanism in which the virus,
      environment and host immune response interact. The influence of the host's
      genetic predisposition to susceptibility or resistance to infectious diseases has
      been evidenced in several studies. The association of the human leukocyte antigen
      gene (HLA) class I alleles with DHF susceptibility or resistance has been
      reported in ethnically and geographically distinct populations. Due to these
      ethnic and viral strain differences, associations occur in each population,
      independently with a specific allele, which most likely explains the associations
      of several alleles with DHF. As the potential role of HLA alleles in the
      progression of DHF in Brazilian patients remains unknown, we then identified HLA
      A alleles in 67 patients with dengue fever and 42 with DHF from Rio de Janeiro,
      Brazil, selected from 2002-2008 by the sequence-based typing technique.
      Statistical analysis revealed an association between the HLA-A*01 allele and DHF
      [odds ratio (OR) = 2.7, p = 0.01], while analysis of the HLA-A*31 allele (OR =
      0.5, p = 0.11) suggested a potential protective role in DHF that should be
      further investigated. This study provides evidence that HLA class I alleles might
      be important risk factors for DHF in Brazilian patients.

PMID- 22415263
TI  - Exploring the association between Trypanosoma cruzi infection in rural
      communities and environmental changes in the southern Gran Chaco.
AB  - The association between land use and land cover changes between 1979-2004 in a
      2.26-million-hectare area south of the Gran Chaco region and Trypanosoma cruzi
      infection in rural communities was analysed. The extent of cultural land, open
      and closed forests and shrubland up to 3,000 m around rural communities in the
      north, northwest and west of the province of Cordoba was estimated using Landsat
      satellite imagery. The T. cruzi prevalence was estimated with a cross-sectional
      serological survey conducted in the rural communities. The land cover showed the
      same patterns in the 1979, 1999 and 2004 satellite imagery in both the northwest
      and west regions, with shrinking regions of cultured land and expanding closed
      forests away from the community. The closed forests and agricultural land
      coverage in the north region showed the same trend as in the northwest and west
      regions in 1979 but not in 1999 or 2004. In the latter two years, the coverage
      remote from the communities was either constant or changed in opposite ways from
      that of the northwest and west regions. The changes in closed forests and
      cultured vegetation alone did not have a significant, direct relationship with
      the occurrence of rural communities with at least one person infected by T.
      cruzi. This study suggests that the overall decrease in the prevalence of T.
      cruzi is a consequence of a combined effect of vector control activities and
      changes in land use and land cover.

PMID- 22415264
TI  - Kinetoplastid membrane protein-11 exacerbates infection with Leishmania
      amazonensis in murine macrophages.
AB  - In Leishmania amazonensis, kinetoplastid membrane protein-11 (KMP-11) expression
      increases during meta-cyclogenesis and is higher in amastigotes than in
      promastigotes, suggesting a role for this protein in the infection of the
      mammalian host. We show that the addition of KMP-11 exacerbates L. amazonensis
      infection in peritoneal macrophages from BALB/c mice by increasing interleukin
      (IL)-10 secretion and arginase activity while reducing nitric oxide (NO)
      production. The doses of KMP-11, the IL-10 levels and the intracellular
      amastigote loads were strongly, positively and significantly correlated. The
      increase in parasite load induced by KMP-11 was inhibited by anti-KMP-11 or anti
      IL-10 neutralising antibodies, but not by isotype controls. The neutralising
      antibodies, but not the isotype controls, were also able to significantly
      decrease the parasite load in macrophages cultured without the addition of KMP
      11, demonstrating that KMP-11-induced exacerbation of the infection is not
      dependent on the addition of exogenous KMP-11 and that the protein naturally
      expressed by the parasite is able to promote it. In this study, the exacerbating
      effect of KMP-11 on macrophage infection with Leishmania is for the first time
      demonstrated, implicating it as a virulence factor in L. amazonensis. The
      stimulation of IL-10 production and arginase activity and the inhibition of NO
      synthesis are likely involved in this effect.

PMID- 22415265
TI  - Histopathological examination of nerve samples from pure neural leprosy patients:
      obtaining maximum information to improve diagnostic efficiency.
AB  - Nerve biopsy examination is an important auxiliary procedure for diagnosing pure
      neural leprosy (PNL). When acid-fast bacilli (AFB) are not detected in the nerve
      sample, the value of other nonspecific histological alterations should be
      considered along with pertinent clinical, electroneuromyographical and laboratory
      data (the detection of Mycobacterium leprae DNA with polymerase chain reaction
      and the detection of serum anti-phenolic glycolipid 1 antibodies) to support a
      possible or probable PNL diagnosis. Three hundred forty nerve samples [144 from
      PNL patients and 196 from patients with non-leprosy peripheral neuropathies
      (NLN)] were examined. Both AFB-negative and AFB-positive PNL samples had more
      frequent histopathological alterations (epithelioid granulomas, mononuclear
      infiltrates, fibrosis, perineurial and subperineurial oedema and decreased
      numbers of myelinated fibres) than the NLN group. Multivariate analysis revealed
      that independently, mononuclear infiltrate and perineurial fibrosis were more
      common in the PNL group and were able to correctly classify AFB-negative PNL
      samples. These results indicate that even in the absence of AFB, these
      histopathological nerve alterations may justify a PNL diagnosis when observed in
      conjunction with pertinent clinical, epidemiological and laboratory data.

PMID- 22415266
TI  - Genetic diversity of NS3 protease from Brazilian HCV isolates and possible
      implications for therapy with direct-acting antiviral drugs.
AB  - The hepatitis C virus (HCV) NS3 protease has been one of the molecular targets of
      new therapeutic approaches. Its genomic sequence variability in Brazilian HCV
      isolates is poorly documented. To obtain more information on the magnitude of its
      genetic diversity, 114 Brazilian HCV samples were sequenced and analysed together
      with global reference sequences. Genetic distance (d) analyses revealed that
      subtype 1b had a higher degree of heterogeneity (d = 0.098) than subtypes 1a (d =
      0.060) and 3a (d = 0.062). Brazilian isolates of subtype 1b were distributed in
      the phylogenetic tree among sequences from other countries, whereas most subtype
      1a and 3a sequences clustered into a single branch. Additional characterisation
      of subtype 1a in clades 1 and 2 revealed that all but two Brazilian subtype 1a
      sequences formed a distinct and strongly supported (approximate likelihood-ratio
      test = 93) group of sequences inside clade 1. Moreover, this subcluster inside
      clade 1 presented an unusual phenotypic characteristic in relation to the
      presence of resistance mutations for macrocyclic inhibitors. In particular, the
      mutation Q80K was found in the majority of clade 1 sequences, but not in the
      Brazilian isolates. These data demonstrate that Brazilian HCV subtypes display a
      distinct pattern of genetic diversity and reinforce the importance of sequence
      information in future therapeutic approaches.

PMID- 22415267
TI  - Retention of a recombinant GFP protein expressed by the yellow fever 17D virus in
      the E/NS1 intergenic region in the endoplasmic reticulum.
AB  - The flaviviral envelope proteins, E protein and precursor membrane protein, are
      mainly associated with the endoplasmic reticulum (ER) through two transmembrane
      (TM) domains that are exposed to the luminal face of this compartment. Their
      retention is associated with the viral assembly process. ER-retrieval motifs were
      mapped at the carboxy terminus of these envelope proteins. A recombinant yellow
      fever (YF) 17D virus expressing the reporter green fluorescent protein (GFP) with
      the stem-anchor (SA) region of E protein fused to its carboxy terminus was
      subjected to distinct genetic mutations in the SA sequence to investigate their
      effect on ER retention. Initially, we introduced progressive deletions of the
      stem elements (H1, CS and H2). In a second set of mutants, the effect of a length
      increase for the first TM anchor region was evaluated either by replacing it with
      the longer TM of human LAMP-1 or by the insertion of the VALLLVA sequence into
      its carboxy terminus. We did not detect any effect on the GFP localisation in the
      cell, which remained associated with the ER. Further studies should be undertaken
      to elucidate the causes of the ER retention of recombinant proteins expressed at
      the intergenic E/NS1 region of the YF 17D virus polyprotein.

PMID- 22415268
TI  - Trichuris sp. from 1,040 +/- 50-year-old Cervidae coprolites from the
      archaeological site Furna do Estrago, Pernambuco, Brazil.
AB  - We present results of the paleoparasitological analysis of Cervidae coprolites
      that were recovered from the archaeological site Furna do Estrago, Pernambuco,
      Brazil. Trichuris sp. eggs were recovered from the coprolite samples dated 1,040
      +/- 50 years before present. This is the first record of Trichuris sp. in
      semiarid Cervidae, unexpectedly recorded in archaeological material.

PMID- 22415269
TI  - Echinococcus granulosus genotypes circulating in alpacas (Lama pacos) and pigs
      (Sus scrofa) from an endemic region in Peru.
AB  - The identification of the genotypes of Echinococcus granulosus present in
      livestock and wild animals within regions endemic for cystic echinococcosis (CE)
      is epidemiologically important. Individual strains display different biological
      characteristics that contribute to outbreaks of CE and that must be taken into
      account in the design of intervention programs. In this study, samples of hydatid
      cysts due to E. granulosus were collected from alpacas (4) in Puno and pigs (8)
      in Ayacucho in Peru, an endemic region for CE. Polymerase chain reaction
      amplification and DNA sequencing of specific regions of the mitochondrial
      cytochrome C oxidase subunit 1 and NADH dehydrogenase subunit 1 genes confirmed
      the presence of a strain common to sheep, the G1 genotype, in alpacas. Two
      different strains of E. granulosus were identified in pigs: the G1 and the G7
      genotypes. This is the first report of the G1 genotype of E. granulosus in
      alpacas in endemic regions of CE in Peru.

PMID- 22415270
TI  - The first report of Aedes (Stegomyia) albopictus in Haiti.
AB  - Aedes albopictus was found in six of the 10 departments of Haiti and in 14 of the
      35 communes surveyed. The survey found the larvae of Ae. albopictus in 13
      different types of containers. Used tires and tins were by far the most common
      breeding sites used by this mosquito species. At the breeding sites, Ae.
      albopictus was associated with other mosquito species, such as Aedes aegypti,
      Culex nigripalpus and Aedes mediovittatus. The highest proportion of association
      was with Ae. aegypti. This study represents the first report of Ae. albopictus in
      Haiti.

PMID- 22415272
TI  - Lysine decarboxylase catalyzes the first step of quinolizidine alkaloid
      biosynthesis and coevolved with alkaloid production in leguminosae.
AB  - Lysine decarboxylase (LDC) catalyzes the first-step in the biosynthetic pathway
      of quinolizidine alkaloids (QAs), which form a distinct, large family of plant
      alkaloids. A cDNA of lysine/ornithine decarboxylase (L/ODC) was isolated by
      differential transcript screening in QA-producing and nonproducing cultivars of
      Lupinus angustifolius. We also obtained L/ODC cDNAs from four other QA-producing
      plants, Sophora flavescens, Echinosophora koreensis, Thermopsis chinensis, and
      Baptisia australis. These L/ODCs form a phylogenetically distinct subclade in the
      family of plant ornithine decarboxylases. Recombinant L/ODCs from QA-producing
      plants preferentially or equally catalyzed the decarboxylation of L-lysine and L
      ornithine. L. angustifolius L/ODC (La-L/ODC) was found to be localized in
      chloroplasts, as suggested by the transient expression of a fusion protein of La
      L/ODC fused to the N terminus of green fluorescent protein in Arabidopsis
      thaliana. Transgenic tobacco (Nicotiana tabacum) suspension cells and hairy roots
      produced enhanced levels of cadaverine-derived alkaloids, and transgenic
      Arabidopsis plants expressing (La-L/ODC) produced enhanced levels of cadaverine,
      indicating the involvement of this enzyme in lysine decarboxylation to form
      cadaverine. Site-directed mutagenesis and protein modeling studies revealed a
      structural basis for preferential LDC activity, suggesting an evolutionary
      implication of L/ODC in the QA-producing plants.

PMID- 22415273
TI  - Acquisition and diversification of cladodes: leaf-like organs in the genus
      Asparagus.
AB  - The genus Asparagus is unusual in producing axillary, determinate organs called
      cladodes, which may take on either a flattened or cylindrical form. Here, we
      investigated the evolution of cladodes to elucidate the mechanisms at play in the
      diversification of shoot morphology. Our observations of Asparagus asparagoides,
      which has leaf-like cladodes, showed that its cladodes are anatomically and
      developmentally similar to leaves but differ in the adaxial/abaxial polarity of
      the vasculature. In addition to the expression of an ortholog of KNAT1,
      orthologous genes that are normally expressed in leaves, asymmetric leaves1 and
      HD-ZIPIII, were found to be expressed in cladode primordia in a leaf-like manner.
      The cylindrical cladodes of Asparagus officinalis showed largely similar
      expression patterns but showed evidence of being genetically abaxialized. These
      results provide evidence that cladodes are modified axillary shoots, suggest that
      the co-option of preexisting gene networks involved in leaf development
      transferred the leaf-like form to axillary shoots, and imply that altered
      expression of leaf polarity genes led to the evolution of cylindrical cladodes in
      the A. officinalis clade.

PMID- 22415274
TI  - Comparative analysis of benzoxazinoid biosynthesis in monocots and dicots:
      independent recruitment of stabilization and activation functions.
AB  - Benzoxazinoids represent preformed protective and allelophatic compounds that are
      found in a multitude of species of the family Poaceae (Gramineae) and occur
      sporadically in single species of phylogenetically unrelated dicots.
      Stabilization by glucosylation and activation by hydrolysis is essential for the
      function of these plant defense compounds. We isolated and functionally
      characterized from the dicot larkspur (Consolida orientalis) the benzoxazinoid
      specific UDP-glucosyltransferase and beta-glucosidase that catalyze the enzymatic
      functions required to avoid autotoxicity and allow activation upon challenge by
      herbivore and pathogen attack. A phylogenetic comparison of these enzymes with
      their counterparts in the grasses indicates convergent evolution by repeated
      recruitment from homologous but not orthologous genes. The data reveal a great
      evolutionary flexibility in recruitment of these essential functions of secondary
      plant metabolism.

PMID- 22415276
TI  - Comparative analysis of platelet-derived microparticles reveals differences in
      their amount and proteome depending on the platelet stimulus.
AB  - Platelet-derived microparticles (PMP) are elevated in a number of disorders (e.g.
      cardiovascular disease and cancer). In the present study, we have carried out a
      high-resolution 2-DE-based proteomic analysis of PMP originated following
      platelet activation with different stimulus. Flow cytometric analysis revealed a
      higher average number of microparticles when platelets are activated with shear
      (1800 s(-1)) compared to 0.5 U/mL thrombin. Regarding the proteomic analysis, 30
      protein features were found to be differentially regulated between shear and
      thrombin groups in the pI 4-7 range, from which 28 were successfully identified
      by MS, corresponding to 26 open-reading frames. Signaling proteins constituted
      the major functional group, including membrane receptors, and adapters. Ingenuity
      Pathways Analysis (IPA) software revealed that 21 of the 26 differentially
      regulated unique proteins identified are part of a common network related to cell
      assembly and organization and cell morphology. Western blotting analyses
      confirmed that Dok-2 and the integrin alpha6 are differentially regulated in PMP
      depending on the platelet stimulus. Interestingly, both proteins participate in
      mechanisms regulating angiogenesis so could be part of PMP regulation of
      endothelial cells function. In conclusion, this study shows that platelets shed
      microparticles in different amounts and with a different proteome depending on
      the stimulus.This article is part of a Special Issue entitled: Integrated omics.

PMID- 22415275
TI  - Regulation of root greening by light and auxin/cytokinin signaling in
      Arabidopsis.
AB  - Tight coordination between plastid differentiation and plant development is best
      evidenced by the synchronized development of photosynthetic tissues and the
      biogenesis of chloroplasts. Here, we show that Arabidopsis thaliana roots
      demonstrate accelerated chlorophyll accumulation and chloroplast development when
      they are detached from shoots. However, this phenomenon is repressed by auxin
      treatment. Mutant analyses suggest that auxin transported from the shoot
      represses root greening via the function of indole-3-acetic acid14, auxin
      response factor7 (ARF7), and ARF19. Cytokinin signaling, on the contrary, is
      required for chlorophyll biosynthesis in roots. The regulation by auxin/cytokinin
      is dependent on the transcription factor long hypocotyl5 (HY5), which is required
      for the expression of key chlorophyll biosynthesis genes in roots. The expression
      of yet another root greening transcription factor, golden2-like2 (GLK2), was
      found to be regulated in opposing directions by auxin and cytokinin. Furthermore,
      both the hormone signaling and the GLK transcription factors modified the
      accumulation of HY5 in roots. Overexpression of GLKs in the hy5 mutant provided
      evidence that GLKs require HY5 to maximize their activities in root greening. We
      conclude that the combination of HY5 and GLKs, functioning downstream of light
      and auxin/cytokinin signaling pathways, is responsible for coordinated expression
      of the key genes in chloroplast biogenesis.

PMID- 22415277
TI  - Identification of potential host proteins for influenza A virus based on
      topological and biological characteristics by proteome-wide network approach.
AB  - A proteome-wide network approach was performed to characterize significant
      patterns of influenza A virus (IAV)-human interactions, and to further identify
      potentially valuable targets for prophylactic and therapeutic interventions.
      Topological analysis demonstrated a strong tendency for IAV to interplay with
      highly connected and central proteins located in sparsely connected sub-networks.
      Additionally, functional analysis based on biological process revealed a number
      of functional groups overrepresented for IAV interactions, in which regulation of
      cell death and apoptosis, and phosphorus metabolic process is the most highly
      enriched. In order to investigate whether these topological and biological
      features are significant enough to distinguish IAV targets from human proteome, a
      discrimination model was constructed based on these features using support vector
      machine coupled with genetic algorithm. The average result of overall prediction
      accuracy is 71.04% by leave-one-out across validation test. The optimized
      classifier was then applied to 9706 human proteins. As a result, 1418 novel genes
      were identified from human interactome, some of which were experimentally
      validated by others' works to be important for IAV infection. The findings
      presented in this study might be important in discovering new drug targets for
      therapeutic treatments as well as revealing topological features and functional
      properties specific for viral infection.

PMID- 22415279
TI  - Focus on patient empowerment.

PMID- 22415278
TI  - Epitope presentation is an important determinant of the utility of antigens
      identified from protein arrays in the development of autoantibody diagnostic
      assays.
AB  - Autoantibodies represent an attractive biomarker for diagnostic assays
      principally due to the stability of immunoglobulin in patient serum facilitating
      measurement with conventional assays. Immune responses to tumorigenesis may
      facilitate detection of ovarian cancer in the early stages of the disease with
      identification of a panel of tumour specific autoantibodies. Despite the
      reporting of many tumour associated autoantibodies using arrays of tumour
      antigens, this has not led to the advance in diagnostic capability as rapidly as
      was initially expected. Here we examine the potential diagnostic utility of
      candidate autoantibody biomarkers identified via screening of serum samples on a
      high content human protein array from a unique cohort of early stage and late
      stage ovarian cancer patients. We analyse the performance of autoantibodies to
      the tumour suppressor protein p53 and the novel autoantigens alpha adducin and
      endosulfine alpha identified in our array screen. Each antigen has different
      performance characteristics using conventional ELISA format and Western blot
      immunoassay. The high attrition rate of promising autoantigens identified by
      array screening can in part be explained by the presentation of the epitope of
      the antigen in the subsequent method of validation and this study provides
      directions on maximising the potential of candidate biomarkers. This article is
      part of a Special Issue entitled: Translational Proteomics.

PMID- 22415280
TI  - On the language and content of patient engagement.

PMID- 22415281
TI  - Patient engagement--what works?
AB  - The recent focus on patient engagement acknowledges that patients have an
      important role to play in their own health care. This includes reading,
      understanding and acting on health information (health literacy), working
      together with clinicians to select appropriate treatments or management options
      (shared decision making), and providing feedback on health care processes and
      outcomes (quality improvement). Various interventions designed to help patients
      play an effective role have been evaluated in trials and systematic reviews. This
      article outlines the evidence in support of the most promising interventions.

PMID- 22415282
TI  - Shared decision making: informing and involving patients to do the right thing in
      health care.
AB  - At the individual level, practicing high-quality medical care means doing the
      right thing for a patient as safely as possible. Some medical decisions have one
      optimal course of action, but most have multiple reasonable options with outcomes
      that will be valued differently by different people. For these preference
      sensitive decisions, involving patients in a shared decision-making process is
      critical. Patient decision aids are tools that help make shared decision making
      practical. Policy changes at the federal and state level can help make shared
      decision making with the active participation of informed patients the rule
      rather than the exception.

PMID- 22415283
TI  - Spreading a patient-centered medical home redesign: a case study.
AB  - Health care leaders and policymakers are turning to the patient-centered medical
      home (PCMH) model to contain costs, improve the quality of care, and create a
      more positive primary care work environment. We describe how Group Health, an
      integrated delivery system, developed and implemented a PCMH intervention that
      included standardized structural and practice level changes. This intervention
      was spread to a diverse set of 26 primary care practices in 14 months using Lean
      Management principles. Group Health's experience provides valuable insights that
      can be used to improve the design and implementation of future PCMH models.

PMID- 22415284
TI  - The medium is the (health) measure: patient engagement using personal
      technologies.
AB  - With the phrase "the medium is the message", Marshall McLuhan argued that
      technologies are the messages themselves and not just the medium. Almost 50 years
      later, we understand that modern information and communication technologies
      expand our ability to perceive our world to an extent that would be impossible
      without the medium. In this article, we contend that information and
      communication technologies are becoming the dominant medium for patient
      engagement. Information and communication technologies will efficiently change
      patient-reported measurement into much more behaviorally sophisticated
      information that will create a very different interaction between patients and a
      new kind of health care workforce.

PMID- 22415285
TI  - International perspectives on patient engagement: results from the 2011
      Commonwealth Fund Survey.
AB  - We analyzed 2011 survey data of patients with complex health care needs in 11
      countries (Australia, Canada, France, Germany, the Netherlands, New Zealand,
      Norway, Sweden, Switzerland, the United Kingdom, and the United States) on their
      care experiences. Wide country variation was reported in how well patients were
      engaged by their clinicians; UK and Swiss patients reported the most positive
      experiences, but gaps were reported in all countries. Disparities by income were
      found in several countries, with the widest gaps reported in the United States.
      Across countries, engaged patients reported receiving higher-quality care, fewer
      errors, and more positive views of the health system.

PMID- 22415286
TI  - The dos and don'ts of patient engagement in busy office practices.

PMID- 22415287
TI  - Return on investment from employment of community health workers.
AB  - Community Health Workers (CHWs) are gaining acceptance in the US health care
      system, but have been subject to challenges as to their "cost-effectiveness."
      This situation is shifting, with a growing body of published evidence as to the
      effectiveness of CHWs, but much of the evidence of cost savings from employing
      CHWs is still unpublished. Return on investment analysis for CHWs must consider a
      range of possible CHW roles and stakeholder points of view. Current trends
      suggest we may be entering a new era of acceptance in which a generally lower
      threshold of evidence is required in proposing the employment of CHWs.

PMID- 22415288
TI  - Patient experience of care in the safety net: current efforts and challenges.
AB  - Measuring patient experience of care fosters the delivery of patient-centered
      services and increases health care quality. Most pay-for-performance and public
      reporting programs focus on care provided to insured populations, excluding the
      uninsured. Using qualitative research methods, we interviewed leaders of
      California safety-net practices to assess how they measure patient experience of
      care and the measurement barriers they encounter. Most had unmet needs for
      assistance with data collection and quality improvement strategies for their
      patient population. Tailored measurement and quality improvement resources,
      coupled with policy mandates to give all patients a voice, would improve the
      quality of patient-centered care in safety-net organizations.

PMID- 22415289
TI  - Characteristics of all, occasional, and frequent emergency department visits due
      to ambulatory care-sensitive conditions in Florida.
AB  - We studied characteristics of all, occasional, and frequent emergency department
      (ED) visits due to ambulatory care-sensitive conditions (ACSCs). We used a cross
      sectional, split-sample design with multivariate logistic regressions using
      encounter-level, all-payer ED data from all Florida hospitals for the year of
      2005. We evaluated associations of key patient characteristics, characteristics
      of ED utilization, and availability of primary care physicians in the area, with
      ED visits for ACSCs. We concluded that factors associated with ED use for ACSCs
      were similar for occasional and frequent ED users. Therefore, universal
      strategies for reduction of ED overutilization by increasing access to,
      timeliness, and quality of primary care for all patients likely to experience
      ACSCs should be used.

PMID- 22415291
TI  - Highly cytotoxic vanadium(V) complexes of salan ligands; insights on the role of
      hydrolysis.
AB  - Vanadium(V) oxo complexes with tetradentate diamine bis(phenolato) "salan"
      ligands of the type LVO(OiPr) (L is salan) with different steric and electronic
      substitutions at the ortho and para positions to the binding phenolato moiety
      were synthesized and their hydrolytic stability and cytotoxicity were analyzed.
      With one exception bearing large steric groups, all complexes examined displayed
      marked cytotoxic activity, comparable to, and often higher than, that of
      cisplatin. While the hydrolytic stability changed significantly depending on the
      substituent at the ortho position relative the O-donor with little effect of para
      substitutions, the cytotoxic activity largely was not affected, and high
      cytotoxicity was recorded also for relatively unstable complexes. Additional
      measurements revealed that the cytotoxicity is largely maintained following pre
      incubation of up to 18 hours of the complexes in the biological medium prior to
      cell addition, suggesting that hydrolysis products might serve as the active
      species. In addition, appreciable cytotoxic activity was measured for an isolated
      hydrolysis product that was analyzed crystallographically to exhibit a dimeric
      structure with bridging oxo ligand where both metal centers are bound to the
      salan ligand, supporting the aforementioned conclusions.

PMID- 22415292
TI  - Myoglobin-directed assemblies of binary monolayers functionalized with
      iminodiacetic acid ligands at the air-water interface through metal coordination
      for multivalent protein binding.
AB  - Myoglobin binding to the binary monolayers composed of sodium hexadecylimino
      diacetate and hexadecanol at the air-water interface by means of metal
      coordination has been investigated using infrared reflection absorption
      spectroscopy (IRRAS). In the absence of Cu(2+), no myoglobin binding to the
      binary monolayers was observed. In the presence of Cu(2+), remarkable myoglobin
      binding to the binary monolayers resulted from the formation of ternary complexes
      of iminodiacetate (IDA)-Cu(2+)-surface histidine. Myoglobin-directed assemblies
      of the binary monolayers facilitated multivalent protein binding through lateral
      rearrangements of the IDA ligands and reorientations of the alkyl chains for
      enhanced protein binding. Myoglobin binding to and desorption from the binary
      monolayers could be readily controlled through metal coordination.

PMID- 22415293
TI  - Effectiveness and cost-effectiveness of sentinel lymph node biopsy compared with
      axillary node dissection in patients with early-stage breast cancer: a decision
      model analysis.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) is less invasive than axillary
      lymph node dissection (ALND) for staging early breast cancer, and has a lower
      risk of arm lymphoedema and similar rates of locoregional recurrence up to 8
      years. This study estimates the longer-term effectiveness and cost-effectiveness
      of SLNB. METHODS: A Markov decision model was developed to estimate the
      incremental quality-adjusted life years (QALYs) and costs of an SLNB-based
      staging and management strategy compared with ALND over 20 years' follow-up. The
      probability and quality-of-life weighting (utility) of outcomes were estimated
      from published data and population statistics. Costs were estimated from the
      perspective of the Australian health care system. The model was used to identify
      key factors affecting treatment decisions. RESULTS: The SLNB was more effective
      and less costly than the ALND over 20 years, with 8 QALYs gained and $883,000
      saved per 1000 patients. The SLNB was less effective when: SLNB false negative
      (FN) rate >13%; 5-year incidence of axillary recurrence after an SLNB FN>19%;
      risk of an SLNB-positive result >48%; lymphoedema prevalence after ALND <14%; or
      lymphoedema utility decrement <0.012. CONCLUSION: The long-term advantage of SLNB
      over ALND was modest and sensitive to variations in key assumptions, indicating a
      need for reliable information on lymphoedema incidence and disutility following
      SLNB. In addition to awaiting longer-term trial data, risk models to better
      identify patients at high risk of axillary metastasis will be valuable to inform
      decision-making.

PMID- 22415294
TI  - Making hard choices easier: a prospective, multicentre study to assess the
      efficacy of a fertility-related decision aid in young women with early-stage
      breast cancer.
AB  - BACKGROUND: Fertility is a priority for many young women with breast cancer.
      Women need to be informed about interventions to retain fertility before
      chemotherapy so as to make good quality decisions. This study aimed to
      prospectively evaluate the efficacy of a fertility-related decision aid (DA).
      METHODS: A total of 120 newly diagnosed early-stage breast cancer patients from
      19 Australian oncology clinics, aged 18-40 years and desired future fertility,
      were assessed on decisional conflict, knowledge, decision regret, and
      satisfaction about fertility-related treatment decisions. These were measured at
      baseline, 1 and 12 months, and were examined using linear mixed effects models.
      RESULTS: Compared with usual care, women who received the DA had reduced
      decisional conflict (beta=-1.51; 95%CI: -2.54 to 0.48; P=0.004) and improved
      knowledge (beta=0.09; 95%CI: 0.01-0.16; P=0.02), after adjusting for education,
      desire for children and baseline uncertainty. The DA was associated with reduced
      decisional regret at 1 year (beta=-3.73; 95%CI: -7.12 to -0.35; P=0.031), after
      adjusting for education. Women who received the DA were more satisfied with the
      information received on the impact of cancer treatment on fertility (P<0.001),
      fertility options (P=0.005), and rated it more helpful (P=0.002), than those who
      received standard care. CONCLUSION: These findings support widespread use of this
      DA shortly after diagnosis (before chemotherapy) among younger breast cancer
      patients who have not completed their families.

PMID- 22415295
TI  - Dissection of stromal and cancer cell-derived signals in melanoma xenografts
      before and after treatment with DMXAA.
AB  - BACKGROUND: The non-malignant cells of the tumour stroma have a critical role in
      tumour biology. Studies dissecting the interplay between cancer cells and stromal
      cells are required to further our understanding of tumour progression and methods
      of intervention. For proof-of-principle of a multi-modal approach to dissect the
      differential effects of treatment on cancer cells and stromal cells, we analysed
      the effects of the stromal-targeting agent 5,6-dimethylxanthenone-4-acetic acid
      on melanoma xenografts. METHODS: Flow cytometry and multi-colour
      immunofluorescence staining was used to analyse leukocyte numbers in xenografts.
      Murine-specific and human-specific multiplex cytokine panels were used to
      quantitate cytokines produced by stromal and melanoma cells, respectively. Human
      and mouse Affymetrix microarrays were used to separately identify melanoma cell
      specific and stromal cell-specific gene expression. RESULTS: 5,6
      Dimethylxanthenone-4-acetic acid activated pro-inflammatory signalling pathways
      and cytokine expression from both stromal and cancer cells, leading to neutrophil
      accumulation and haemorrhagic necrosis and a delay in tumour re-growth of 26 days
      in A375 melanoma xenografts. CONCLUSION: 5,6-Dimethylxanthenone-4-acetic acid and
      related analogues may potentially have utility in the treatment of melanoma. The
      experimental platform used allowed distinction between cancer cells and stromal
      cells and can be applied to investigate other tumour models and anti-cancer
      agents.

PMID- 22415298
TI  - Fetal programming: maternal nutrition and role of one-carbon metabolism.
AB  - India is world's capital for low birth weight (LBW), which is ascribed to
      intrauterine growth restriction (IUGR) rather than prematurity. An average Indian
      mother is short and thin and gives birth to a light and thin baby. Maternal
      undernutrition is thought to be a major factor in the aetiology of IUGR, and the
      undernutrition is usually thought to be a low macronutrient intake. The Pune
      Maternal Nutrition Study (PMNS) showed that the Indian babies were thin but fat
      (more adipose) compared to European babies, and that maternal intake of
      micronutrient-rich foods was a strong determinant of fetal size. Two thirds of
      the mothers had low vitamin B(12) concentrations, folate deficiency was rare, and
      high circulating concentrations of homocysteine predicted IUGR. Follow up of
      these children revealed that higher maternal folate in pregnancy predicted higher
      adiposity and insulin resistance at 6 years of age. The most insulin resistant
      children were born to mothers who were vitamin B(12) deficient and had high
      folate concentrations. Thus, PMNS suggests an important role for maternal one
      carbon (1C) metabolism in fetal growth and programming of diabetes risk. This
      could be due to the role of 1C metabolism in synthesis of nucleic acids, genomic
      stability and the epigenetic regulation of gene function. In addition, methionine
      has important role in protein synthesis. These ideas are supported by animal
      studies. The next logical step in India will be to improve 1C metabolism in
      adolescents to effect intergenerational prevention of adiposity, diabetes and
      other related conditions.

PMID- 22415297
TI  - Mechanisms affecting neuroendocrine and epigenetic regulation of body weight and
      onset of puberty: potential implications in the child born small for gestational
      age (SGA).
AB  - Signaling peptides produced in peripheral tissues such as gut, adipose tissue,
      and pancreas communicate with brain centers, such as hypothalamus and hindbrain
      to manage energy homeostasis. These regulatory mechanisms of energy intake and
      storage have evolved during long periods of hunger in the evolution of man to
      protect the species from extinction. It is now clear that these circuitries are
      influenced by prenatal and postnatal environmental factors including endocrine
      disruptive chemicals. Hypothalamic appetite regulatory systems develop and mature
      in utero and early infancy, and involve signaling pathways that are important
      also for the regulation of puberty onset. Recent studies in humans and animals
      have shown that metabolic pathways involved in regulation of growth, body weight
      gain and sexual maturation are largely affected by epigenetic programming that
      can impact both current and future generations. In particular, intrauterine and
      early infantile developmental phases of high plasticity are susceptible to
      factors that affect metabolic programming that therefore, affect metabolic
      function throughout life. In children born small for gestational age, poor
      nutritional conditions during gestation can modify metabolic systems to adapt to
      expectations of chronic undernutrition. These children are potentially poorly
      equipped to cope with energy-dense diets and are possibly programmed to store as
      much energy as possible, leading to later obesity, metabolic syndrome, disturbed
      regulation of normal puberty and early onset of cardiovascular disease. Most
      cases of disturbed energy balance are likely a result of a combination of
      genetics, epigenetics and environment. This review will discuss potential
      mechanisms linking intrauterine growth retardation with changes in growth, energy
      homeostasis and sexual maturation.

PMID- 22415299
TI  - Catch up growth in low birth weight infants: striking a healthy balance.
AB  - Catch-up growth in the first few months of life is seen almost ubiquitously in
      infants born small for their gestational age and conventionally considered highly
      desirable as it erases the growth deficit. However, recently such growth has been
      linked to an increased risk of later adiposity, insulin resistance and
      cardiovascular disease in both low income and high-income countries. In India, a
      third of all babies are born with a low birth weight, but the optimal growth
      pattern for such infants is uncertain. As a response to the high rates of
      infectious morbidities, undernutrition and stunting in children, the current
      policy is to promote rapid growth in infancy. However, with socio-economic
      transition and urbanization making the Indian environment more obesogenic, and
      the increasing prevalence of type 2 diabetes and cardiovascular disease,
      affecting progressively younger population, the long term adverse programming
      effect of fast/excessive weight gain in infancy on later body composition and
      metabolism may outweigh short-term benefits. This review discusses the above
      issues focusing on the need to strike a healthy balance between the risks and
      benefits of catch-up growth in Indian infants.

PMID- 22415300
TI  - Identification and expression of a novel member of Ly-6 superfamily in zebrafish
      Denio rerio.
AB  - Ly-6 superfamily members are present in many metazoans and are divided into two
      groups: secreted proteins and glycosylphosphatidyl inositol (GPI)-anchored
      membrane proteins. They both contain one or more conserved domain identified as
      Ly-6/uPAR (LU) domain and play key roles in cellular adhesion and signaling.
      Here, we identify a novel member, lymphocyte antigen-6 epidermis (lye), of Ly-6
      superfamily in zebrafish. In silico analyses revealed that lye codes for a
      predicted GPI-anchored membrane protein containing a conserved LU domain and 10
      position-specific conserved cysteines typical of known Ly-6 proteins. Whole mount
      in situ hybridization showed that lye is predominantly expressed in epidermis. We
      thus named the gene lye, highlighting it is expressed in epidermis. Lye exhibits
      a dynamic expression pattern during development, which is initially expressed in
      enveloping layer at gastrula stage, then expressed in epidermis at later stages.
      It is also expressed in olfactory placode at 24 h post-fertilization.
      Subsequently, epidermal expression of lye becomes weaker gradually, whereas the
      expression in pharyngeal arch and pectoral fin increases at 2 and 3 days post
      fertilization. Our study lays a foundation for further investigation of lye roles
      in early developmental stages.

PMID- 22415301
TI  - Myc-associated zinc finger protein (MAZ) is regulated by miR-125b and mediates
      VEGF-induced angiogenesis in glioblastoma.
AB  - In patients with glioblastomas, vascular endothelial growth factor (VEGF) is a
      key mediator of tumor-associated angiogenesis. Glioblastomas are notorious for
      their capacity to induce neovascularization, driving continued tumor growth. Here
      we report that miR-125b is down-regulated in glioblastoma-associated endothelial
      cells, resulting in increased expression of its target, myc-associated zinc
      finger protein (MAZ), a transcription factor that regulates VEGF. The down
      regulation of miR-125b was also observed on exposure of endothelial cells to
      glioblastoma-conditioned medium or VEGF, resulting in increased MAZ expression.
      Further analysis revealed that inhibition of MAZ accumulation by miR-125b, or by
      MAZ-specific shRNAs, attenuated primary human brain endothelial cell migration
      and tubule formation in vitro, phenomena considered to mimick angiogenic
      processes in vitro. Moreover, MAZ expression was elevated in brain blood vessels
      of glioblastoma patients. Altogether these results demonstrate a functional feed
      forward loop in glioblastoma-related angiogenesis, in which VEGF inhibits the
      expression of miR-125b, resulting in increased expression of MAZ, which in its
      turn causes transcriptional activation of VEGF. This loop is functionally impeded
      by the VEGF receptor inhibitor vandetanib, and our results may contribute to the
      further development of inhibitors of tumor-angiogenesis.

PMID- 22415302
TI  - Blunted epidermal L-tryptophan metabolism in vitiligo affects immune response and
      ROS scavenging by Fenton chemistry, part 1: Epidermal H2O2/ONOO(-)-mediated
      stress abrogates tryptophan hydroxylase and dopa decarboxylase activities,
      leading to low serotonin and melatonin levels.
AB  - Vitiligo is characterized by a progressive loss of inherited skin color. The
      cause of the disease is still unknown. To date, there is accumulating in vivo and
      in vitro evidence for massive oxidative stress via hydrogen peroxide (H(2)O(2))
      and peroxynitrite (ONOO(-)) in the skin of affected individuals. Autoimmune
      etiology is the favored theory. Since depletion of the essential amino acid L
      tryptophan (Trp) affects immune response mechanisms, we here looked at epidermal
      Trp metabolism via tryptophan hydroxylase (TPH) with its downstream cascade,
      including serotonin and melatonin. Our in situ immunofluorescence and Western
      blot data reveal significantly lower TPH1 expression in patients with vitiligo.
      Expression is also low in melanocytes and keratinocytes under in vitro
      conditions. Although in vivo Fourier transform-Raman spectroscopy proves the
      presence of 5-hydroxytryptophan, epidermal TPH activity is completely absent.
      Regulation of TPH via microphthalmia-associated transcription factor and L-type
      calcium channels is severely affected. Moreover, dopa decarboxylase (DDC)
      expression is significantly lower, in association with decreased serotonin and
      melatonin levels. Computer simulation supports H(2)O(2)/ONOO(-)-mediated
      oxidation/nitration of TPH1 and DDC, affecting, in turn, enzyme functionality.
      Taken together, our data point to depletion of epidermal Trp by Fenton chemistry
      and exclude melatonin as a relevant contributor to epidermal redox balance and
      immune response in vitiligo.

PMID- 22415303
TI  - The A2B adenosine receptor modulates pulmonary hypertension associated with
      interstitial lung disease.
AB  - Development of pulmonary hypertension is a common and deadly complication of
      interstitial lung disease. Little is known regarding the cellular and molecular
      mechanisms that lead to pulmonary hypertension in patients with interstitial lung
      disease, and effective treatment options are lacking. The purpose of this study
      was to examine the adenosine 2B receptor (A(2B)R) as a regulator of vascular
      remodeling and pulmonary hypertension secondary to pulmonary fibrosis. To
      accomplish this, cellular and molecular changes in vascular remodeling were
      monitored in mice exposed to bleomycin in conjunction with genetic removal of the
      A(2B)R or treatment with the A(2B)R antagonist GS-6201. Results demonstrated that
      GS-6201 treatment or genetic removal of the A(2B)R attenuated vascular remodeling
      and hypertension in our model. Furthermore, direct A(2B)R activation on vascular
      cells promoted interleukin-6 and endothelin-1 release. These studies identify a
      novel mechanism of disease progression to pulmonary hypertension and support the
      development of A(2B)R antagonists for the treatment of pulmonary hypertension
      secondary to interstitial lung disease.

PMID- 22415304
TI  - Mycobacterium tuberculosis Rv0577, a novel TLR2 agonist, induces maturation of
      dendritic cells and drives Th1 immune response.
AB  - Tuberculosis (TB) caused by Mycobacterium tuberculosis constitutes an ongoing
      threat to global health. An antigen that can induce dendritic cell (DC)
      maturation and lead to enhanced cellular immunity is crucial to the development
      of an effective TB vaccine. Here, we investigated the functional roles and the
      related signaling mechanism of the Rv0577 protein, a M. tuberculosis complex
      restricted secreted protein involved in the methylglyoxal detoxification pathway.
      Rv0577 recognizes Toll-like receptor 2 (TLR2) and functionally induces DC
      maturation by augmenting the expression of cell surface molecules (CD80, CD86,
      and MHC class I and II) and proinflammatory cytokine production (TNF-alpha, IL
      1beta, IL-6, and IL-12p70) in DCs on MyD88-dependent signaling, mitogen-activated
      protein kinases, and nuclear factor kappaB signaling pathways. In addition,
      Rv0577-treated DCs activated naive T cells, effectively polarized CD4(+) and
      CD8(+) T cells to secrete IFN-gamma and IL-2, and induced T-cell proliferation,
      indicating that this protein possibly contributes to Th1-polarization of the
      immune response. More important, unlike LPS, Rv0577-treated DCs specifically
      induced the proliferation of memory CD4(+)/CD8(+)CD44(high)CD62L(low) T cells in
      the spleen of M. tuberculosis-infected mice in a TLR2-dependent manner. Taken
      together, these findings suggest that Rv0577 may regulate innate and adaptive
      immunity by interacting with TLR2, a finding that could be helpful in the design
      of new TB vaccines.

PMID- 22415305
TI  - Overexpression of AMP-metabolizing enzymes controls adenine nucleotide levels and
      AMPK activation in HEK293T cells.
AB  - We investigated whether overexpression of AMP-metabolizing enzymes in intact
      cells would modulate oligomycin-induced AMPK activation. Human embryonic kidney
      (HEK) 293T cells were transiently transfected with increasing amounts of plasmid
      vectors to obtain a graded increase in overexpression of AMP-deaminase (AMPD) 1,
      AMPD2, and soluble 5'-nucleotidase IA (cN-IA) for measurements of AMPK activation
      and total intracellular adenine nucleotide levels induced by oligomycin
      treatment. Overexpression of AMPD1 and AMPD2 slightly decreased AMP levels and
      oligomycin-induced AMPK activation. Increased overexpression of cN-IA led to
      reductions in the oligomycin-induced increases in AMP and ADP concentrations by
      ~70 and 50%, respectively, concomitant with a 50% decrease in AMPK activation.
      The results support the view that a rise in ADP as well as AMP is important for
      activation of AMPK, which can thus be regulated by the adenylate energy charge.
      The control coefficient of cN-IA on AMP was 0.3-0.7, whereas the values for AMPD1
      and AMPD2 were <0.1, suggesting that in this model cN-IA exerts a large
      proportion of control over intracellular AMP. Therefore, small molecule
      inhibition of cN-IA could be a strategy for AMPK activation.

PMID- 22415306
TI  - Blunted epidermal L-tryptophan metabolism in vitiligo affects immune response and
      ROS scavenging by Fenton chemistry, part 2: Epidermal H2O2/ONOO(-)-mediated
      stress in vitiligo hampers indoleamine 2,3-dioxygenase and aryl hydrocarbon
      receptor-mediated immune response signaling.
AB  - Vitiligo is characterized by a mostly progressive loss of the inherited skin
      color. The cause of the disease is still unknown, despite accumulating in vivo
      and in vitro evidence of massive oxidative stress via hydrogen peroxide
      (H(2)O(2)) and peroxynitrite (ONOO(-)) in the skin of affected individuals. The
      most favored hypothesis is based on autoimmune mechanisms. Since depletion of the
      essential amino acid L-tryptophan (Trp) severely affects various immune
      responses, we here looked at Trp metabolism and signaling in these patients. Our
      in vivo and in vitro data revealed total absence of epidermal Trp hydroxylase
      activities and the presence of H(2)O(2)/ONOO(-) deactivated indoleamine 2,3
      dioxygenase. Aryl hydrocarbon receptor signaling is severely impaired despite the
      ligand (Trp dimer) being formed, as shown by mass spectrometry. Loss of this
      signal is supported by the absence of downstream signals (COX-2 and CYP1A1) as
      well as regulatory T-lymphocytes and by computer modeling. In vivo Fourier
      transform Raman spectroscopy confirmed the presence of Trp metabolites together
      with H(2)O(2) supporting deprivation of the epidermal Trp pool by Fenton
      chemistry. Taken together, our data support a long-expressed role for in loco
      redox balance and a distinct immune response. These insights could open novel
      treatment strategies for this disease.

PMID- 22415307
TI  - Biochemical and mechanical environment cooperatively regulate skeletal muscle
      regeneration.
AB  - During forelimb regeneration in the newt Notophthalmus viridescens, the dynamic
      expression of a transitional matrix rich in hyaluronic acid, tenascin-C, and
      fibronectin controls muscle cell behavior in vivo and in vitro. However, the
      influence of extracellular matrix (ECM) remodeling on tissue stiffness and the
      cellular response to mechanical variations during regeneration was unknown. By
      measuring the transverse stiffness of tissues in situ, we found undifferentiated
      regenerative blastemas were less stiff than differentiated stump muscle (13.3+/
      1.6 vs. 16.6+/-1.2 kPa). To directly determine how ECM and stiffness combine to
      affect skeletal muscle fragmentation, migration, and fusion, we coated silicone
      based substrates ranging from 2 to 100 kPa with matrices representative of
      transitional (tenascin-C and fibronectin) and differentiated environments
      (laminin and Matrigel). Using live-cell imaging, we found softer tenascin-C
      coated substrates significantly enhanced migration and fragmentation of primary
      newt muscle cells. In contrast, stiffer substrates coated with laminin, Matrigel,
      or fibronectin increased differentiation while suppressing migration and
      fragmentation. These data support our in vivo observations that a transitional
      matrix of reduced stiffness regulates muscle plasticity and progenitor cell
      recruitment into the regenerative blastema. These new findings will enable the
      determination of how biochemical and mechanical cues from the ECM control genetic
      pathways that drive regeneration.

PMID- 22415308
TI  - Divergent roles of CD44 and carcinoembryonic antigen in colon cancer metastasis.
AB  - After separating from a primary tumor, metastasizing cells enter the circulatory
      system and interact with host cells before lodging in secondary organs. Previous
      studies have implicated the surface glycoproteins CD44 and carcinoembryonic
      antigen (CEA) in adhesion, migration, and invasion, suggesting that they may
      influence metastatic progression. To elucidate the role of these multifunctional
      molecules while avoiding the potential drawbacks of ectopic expression or
      monoclonal antibody treatments, we silenced the expression of CD44 and/or CEA in
      LS174T colon carcinoma cells and analyzed their ability to metastasize in 2
      independent mouse models. Quantitative PCR revealed that CD44 knockdown increased
      lung and liver metastasis >10-fold, while metastasis was decreased by >50%
      following CEA knockdown. These findings were corroborated by in vitro experiments
      assessing the metastatic potential of LS174T cells. Cell migration was decreased
      as a result of silencing CEA but was enhanced in CD44-knockdown cells. In
      addition, CD44 silencing promoted homotypic aggregation of LS147T cells, a
      phenotype that was reversed by additional CEA knockdown. Finally, CD44-knockdown
      cells exhibited greater mechanical compliance than control cells, a property that
      correlates with increased metastatic potential. Collectively, these data indicate
      that CEA, but not CD44, is a viable target for therapeutics aimed at curbing
      colon carcinoma metastasis.

PMID- 22415309
TI  - Hypoxia induces IGFBP3 in esophageal squamous cancer cells through HIF-1alpha
      mediated mRNA transcription and continuous protein synthesis.
AB  - Insulin-like growth factor binding protein (IGFBP)-3 regulates cell proliferation
      and apoptosis in esophageal squamous cell carcinoma (ESCC) cells. We have
      investigated how the hypoxic tumor microenvironment in ESCC fosters the induction
      of IGFBP3. RNA interference experiments revealed that hypoxia-inducible factor
      (HIF)-1alpha, but not HIF-2alpha, regulates IGFBP3 mRNA induction. By chromatin
      immunoprecipitation and transfection assays, HIF-1alpha was found to
      transactivate IGFBP3 through a novel hypoxia responsive element (HRE) located at
      57 kb upstream from the transcription start site. Metabolic labeling experiments
      demonstrated hypoxia-mediated inhibition of global protein synthesis. 7-Methyl
      GTP-cap binding assays suggested that hypoxia suppresses cap-dependent
      translation. Experiments using pharmacological inhibitors for mammalian target of
      rapamycin (mTOR) suggested that a relatively weak mTOR activity may be sufficient
      for cap-dependent translation of IGFBP3 under hypoxic conditions. Bicistronic RNA
      reporter transfection assays did not validate the possibility of an internal
      ribosome entry site as a potential mechanism for cap-independent translation for
      IGFBP3 mRNA. Finally, IGFBP3 mRNA was found enriched to the polysomes. In
      aggregate, our study establishes IGFBP3 as a direct HIF-1alpha target gene and
      that polysome enrichment of IGFBP3 mRNA may permit continuous translation under
      hypoxic conditions.

PMID- 22415310
TI  - ATP released from cardiac fibroblasts via connexin hemichannels activates
      profibrotic P2Y2 receptors.
AB  - Cardiac fibroblasts (CFs) play an essential role in remodeling of the cardiac
      extracellular matrix. Extracellular nucleotide signaling may provoke a
      profibrotic response in CFs. We tested the hypothesis that physical perturbations
      release ATP from CFs and that ATP participates in profibrotic signaling. ATP
      release was abolished by the channel inhibitor carbenoxolone and inhibited by
      knockdown of either connexin (Cx)43 or Cx45 (47 and 35%, respectively), implying
      that hypotonic stimulation induces ATP release via Cx43 and Cx45 hemichannels,
      although pannexin 1 may also play a role. ATP released by hypotonic stimulation
      rapidly (<10 min) increased phosphorylated ERK by 5-8 fold, an effect largely
      eliminated by P2Y(2) receptor knockdown or ATP hydrolysis with apyrase. ATP
      stimulation of P2Y(2) receptors increased alpha-smooth muscle actin (alpha-SMA)
      production, and in an ERK-dependent manner, ATP increased collagen accumulation
      by 60% and mRNA expression of profibrotic markers: plasminogen activator
      inhibitor-1 and monocyte chemotactic protein-1 by 4.5- and 4.0-fold,
      respectively. Apyrase treatment substantially reduced the basal profibrotic
      phenotype, decreasing collagen and alpha-SMA content and increasing matrix
      metalloproteinase expression. Thus, ATP release activates P2Y(2) receptors to
      mediate profibrotic responses in CFs, implying that nucleotide release under both
      basal and activated states is likely an important mechanism for fibroblast
      homeostasis.

PMID- 22415311
TI  - Hepatic induction of cholesterol biosynthesis reflects a remote adaptive response
      to pneumococcal pneumonia.
AB  - Community-acquired pneumonia presents a spectrum of clinical phenotypes, from
      lobar pneumonia to septic shock, while mechanisms underlying progression are
      incompletely understood. In a transcriptomic and metabolomic study across
      tissues, we examined serotype-specific regulation of signaling and metabolic
      pathways in C57BL/6 mice intratracheally instilled with either serotype 19F
      Streptococcus pneumoniae (S19; causing lobar pneumonia), or serotype 2 S.
      pneumoniae (S2; causing septic pneumococcal disease,) or vehicle (Todd-Hewitt
      broth). Samples of lung, liver, and blood were collected at 6 and 24 h
      postinfection and subjected to microarray analysis and mass spectrometry. Results
      comprise a preferential induction of cholesterol biosynthesis in lobar pneumonia
      at low-infection doses (10(5) colony forming units/mouse) leading to increased
      plasma cholesterol (vehicle: 1.8+/-0.12 mM, S2: 2.3+/-0.10 mM, S19: 2.9+/-0.15
      mM; P<0.05, comparing S19 to vehicle and S2). This induction was pneumolysin
      dependent, as a pneumolysin-deficient strain of serotype 19F failed to induce
      cholesterol biosynthesis (S19DeltaPLY: 1.9+/-0.03 mM). Preincubation of
      pneumolysin with purified cholesterol or plasma from hypercholesterolemic mice
      prior to intratracheal instillation protected against lung barrier dysfunction
      and alveolar macrophage necrosis. Cholesterol may attenuate disease severity by
      neutralizing pneumolysin in the alveolar compartment and thus prevent septic
      disease progression.

PMID- 22415313
TI  - Relevance of birth cohorts to assessment of asthma persistence.
AB  - The definition of persistent asthma in longitudinal studies reflects symptoms
      reported at every assessment with no substantive asymptomatic periods. Early
      childhood wheezing may be transient, especially if it is of viral etiology.
      Longitudinal studies provide greater opportunity to confirm the diagnosis by
      variability of symptoms, objective measurements, and therapeutic responses.
      Several clinical phenotypes of childhood asthma have been identified, with
      general consistency between cohorts. Persistent wheezing is often associated with
      loss of lung function, which is evident from early-childhood and related to
      persistent inflammation and airway hyperresponsiveness. Female sex, atopy, airway
      responsiveness, and personal smoking, but not exposure to environmental tobacco
      smoke, are risk factors for persistence of childhood asthma into adulthood. The
      effect of breastfeeding remains controversial, but gene-environment interactions
      may partly explain outcomes. Understanding the natural history and underlying
      causes of asthma may lead to development of strategies for primary prevention.

PMID- 22415314
TI  - Spleen cells from young but not old immunized mice eradicate large established
      cancers.
AB  - PURPOSE: Solid tumors that have grown two weeks or longer in mice and have
      diameters larger than 1 cm are histologically indistinguishable from
      autochthonous human cancers. When experimental tumors reach this clinically
      relevant size, they are usually refractory to most immunotherapies but may be
      destroyed by adoptive T-cell transfer. However, TCR-transgenic T cells and/or
      tumor cells overexpressing antigens are frequently used in these experiments.
      Here we studied the requirements for destroying clinical size, unmanipulated 8101
      tumors by adoptive cell therapy. EXPERIMENTAL DESIGN: 8101 arose in an old mouse
      after chronic exposure to UV light. A cancer line was established, which was
      never serially transplanted. The immunodominant CD8(+) T cell-recognized antigen
      of this tumor is caused by a somatic tumor-specific mutation in the RNA helicase
      p68. 8101 tumors were treated with spleen cells from young naive, or young and
      old immunized mice to ascertain the characteristics of immune cells that lead to
      rejection. RESULTS: Here we show that the mutant p68 peptide has an exceptionally
      high affinity to the presenting MHC class I molecule K(b) and that spleen cells
      from immunized young syngeneic mice adoptively transferred to Rag(-/-) or cancer
      suppressed euthymic mice eradicate 8101 tumors larger than 1 cm in average
      diameter and established for several weeks. Spleen cells from naive young mice or
      from old and boosted (reimmunized) mice were ineffective. CONCLUSIONS: Relapse
      free destruction of large and long-established tumors expressing a genuine very
      high-affinity tumor-specific antigen can be achieved by using adoptive transfer
      of lymphocytes from immunized young individuals.

PMID- 22415315
TI  - Molecular pathways: the role of primary cilia in cancer progression and
      therapeutics with a focus on Hedgehog signaling.
AB  - Abnormal Hedgehog (Hh) pathway activity has been reported in many cancers,
      including basal cell carcinomas, medulloblastomas, rhabdomyosarcomas,
      glioblastomas, and breast and prostate cancers. For this reason, the Hh pathway
      is a flourishing area for development of anticancer drugs such as Hh ligand
      antagonists (e.g., 5E1 and robotnikinin), Smo inhibitors (e.g., GDC-0449 and IPI
      926), and Gli transcriptional activity inhibitors (e.g., GANT58 and GANT61). It
      is now clear that primary cilia are required for activation of the Hh pathway in
      normal vertebrate cells. It is in the primary cilium that both positive and
      negative effectors of the Hh pathway are processed by posttranslational
      modifications. In many cancers, preliminary results suggest that primary cilia
      are lost. As drugs that inhibit different steps of the Hh pathway are developed,
      it will be important to consider how these drugs will function in the context of
      primary cilia in the tumor environment. Here, we discuss why some of the Hh
      inhibitors may be ineffective if primary cilia are lost on cancer cells.
      Understanding the relationships between clinical inhibitors of the Hh pathway and
      the presence or absence of primary cilia may turn out to be critical for
      targeting these therapeutics to the correct population of patients and improving
      their efficacy. Further work is needed in this area to maximize the potential of
      these exciting therapeutic targets.

PMID- 22415316
TI  - IDH mutation and neuroglial developmental features define clinically distinct
      subclasses of lower grade diffuse astrocytic glioma.
AB  - PURPOSE: Diffuse gliomas represent the most prevalent class of primary brain
      tumor. Despite significant recent advances in the understanding of glioblastoma
      [World Health Organization (WHO) IV], its most malignant subtype, lower grade
      (WHO II and III) glioma variants remain comparatively understudied, especially in
      light of their notable clinical heterogeneity. Accordingly, we sought to identify
      and characterize clinically relevant molecular subclasses of lower grade diffuse
      astrocytic gliomas. EXPERIMENTAL DESIGN: We conducted multidimensional molecular
      profiling, including global transcriptional analysis, on 101 lower grade diffuse
      astrocytic gliomas collected at our own institution and validated our findings
      using publically available gene expression and copy number data from large
      independent patient cohorts. RESULTS: We found that IDH mutational status
      delineated molecularly and clinically distinct glioma subsets, with IDH mutant
      (IDH mt) tumors exhibiting TP53 mutations, platelet-derived growth factor
      receptor (PDGFR)A overexpression, and prolonged survival, and IDH wild-type (IDH
      wt) tumors exhibiting EGFR amplification, PTEN loss, and unfavorable disease
      outcome. Furthermore, global expression profiling revealed three robust molecular
      subclasses within lower grade diffuse astrocytic gliomas, two of which were
      predominantly IDH mt and one almost entirely IDH wt. IDH mt subclasses were
      distinguished from each other on the basis of TP53 mutations, DNA copy number
      abnormalities, and links to distinct stages of neurogenesis in the subventricular
      zone. This latter finding implicates discrete pools of neuroglial progenitors as
      cells of origin for the different subclasses of IDH mt tumors. CONCLUSION: We
      have elucidated molecularly distinct subclasses of lower grade diffuse astrocytic
      glioma that dictate clinical behavior and show fundamental associations with both
      IDH mutational status and neuroglial developmental stage.

PMID- 22415317
TI  - Kidney and hypertension: is there a place for renalase?
AB  - Chronic kidney disease (CKD) is associated with a considerably higher risk of
      cardiovascular disease due to the presence of traditional and nontraditional risk
      factors. Hypertension occurs in approximately 80% to 85% of the patients with CKD
      and its etiology is multifactorial. The sympathetic nervous system activity is
      enhanced in patients witch CKD resulting in increased vascular resistance and
      systemic blood pressure. This enhanced activity is the result of overspill and
      reduced catecholamine clearance. Recently, a new protein was discovered, named
      renalase. Experimental in vitro studies showed that renalase degrades
      catecholamines and thus may have a significant hemodynamic effect in vivo, for
      example may decrease cardiac contractility, heart rate, and blood pressure.
      Studies conducted in CKD and hemodialysis patients demonstrated lower serum
      renalase levels compared with healthy individuals. Other studies revealed
      increased serum renalase levels in dialysis population and kidney transplant
      recipients. There are no data concerning the association between renalase gene
      expression and activity/concentration and function of renalase; thus, it has to
      be proved in further studies that renalase is not an innocent bystander but is
      involved in the pathogenesis of hypertension.

PMID- 22415318
TI  - Relation between projection positions and X-ray radiation doses during placement
      of the coronary sinus mapping electrode.
AB  - PURPOSE: To reduce X-ray radiation injury, we investigated the relation between
      projection positions and X-ray radiation doses when a coronary sinus mapping
      electrode was placed. METHODS: There were 400 patients in whom a coronary sinus
      mapping electrode was placed for intracardiac electrophysiologic examination or
      radio-frequency catheter ablation in our hospital between 1 June 2008 and 31 May
      2011. The doctors who placed the coronary sinus mapping electrode and the
      projection positions including posteroanterior, left anterior oblique 45 degrees
      , and right anterior oblique 30 degrees  projection positions were randomly
      selected. X-ray doses were recorded when the coronary sinus mapping electrode was
      placed, and then, these were compared between the three projection positions.
      RESULTS: The X-ray dose was significantly lower in the right anterior oblique 30
      degrees  projection position (50.01 +/- 11.38 mGy) than in the posteroanterior
      projection position (68.05 +/- 18.85 mGy, q = 12.924, p = 0.000) and the left
      anterior oblique 45 degrees  projection position (71.66 +/- 16.95 mGy, q =
      15.214, p = 0.000). There were no statistical significances in X-ray doses
      between the posteroanterior and the left anterior oblique 45 degrees  projection
      positions (p = 0.066) and different operators (p = 0.985). CONCLUSION: Based on
      the results of this study, we suggest that in placing the coronary sinus mapping
      electrode, the right anterior oblique 30 degrees  projection position should be
      first adopted because it can allow the electrode to be easily placed and reduce
      the X-ray radiation dose as much as possible.

PMID- 22415320
TI  - Synchronous Embryonal Rhabdomyosarcoma (NOS) of the Mid-oesophagus and Stomach.

PMID- 22415319
TI  - Animal models of peripheral neuropathies.
AB  - Peripheral neuropathies are common neurological diseases, and various animal
      models have been developed to study disease pathogenesis and test potential
      therapeutic drugs. Three commonly studied disease models with huge public health
      impact are diabetic peripheral neuropathy, chemotherapy-induced peripheral
      neuropathy, and human immunodeficiency virus-associated sensory neuropathies. A
      common theme in these animal models is the comprehensive use of pathological,
      electrophysiological, and behavioral outcome measures that mimic the human
      disease. In recent years, the focus has shifted to the use of outcome measures
      that are also available in clinical use and can be done in a blinded and
      quantitative manner. One such evaluation tool is the evaluation of epidermal
      innervation with a simple skin biopsy. Future clinical trials will be needed to
      validate the translational usefulness of this outcome measure and validation
      against accepted outcome measures that rely on clinical symptoms or examination
      findings in patients.

PMID- 22415321
TI  - Cytotoxic effect of freeze-dried extract of Ecballium elaterium fruit on gastric
      adenocarcinoma (AGS) and esophageal squamous cell carcinoma (KYSE30) cell lines.
AB  - PURPOSE: Ecballium elaterium (L.) A. Rich (Cucurbitaceae), also known as the
      "squirting cucumber," is a wild medicinal plant found abundantly in Moghan,
      Ardabil province, Iran. This study was undertaken to examine possible cytotoxic
      effect of freeze-dried aqueous extract of E. elaterium fruit on cell lines of
      gastric and esophageal origin namely called AGS (human gastric carcinoma) and
      KYSE30 (human esophageal squamous cell carcinoma). METHODS: The aqueous extract
      of the fruits of E. elaterium was prepared and freeze-dried. AGS and KYSE30
      cancer cell lines were treated by the extract and incubated for 24, 48, and 72 h.
      Cytotoxicity was examined by MTT assay. Ethidium bromide/acridine orange (EB/AO)
      staining was used for apoptotic cell detection. A DAPI staining method was used
      to analyze cell cycle by flow cytometry. RESULTS: The IC(50) values were 2.5,
      0.7, and 0.7 MUg/ml for AGS cell line after 24, 48, and 72 h, respectively.
      IC(50) values for KYSE30 cell line were 500, 150, and 125 MUg/ml after 24, 48,
      and 72 h, respectively. The EB/AO staining showed an increase in apoptotic cells.
      Cell cycle analysis showed a significant increase in cell density at G2/M phase.
      CONCLUSIONS: The results of the current study showed that the freeze-dried
      aqueous extract of E. elaterium fruit has a cytotoxic effect on gastric and
      esophageal cancer cell lines by means of apoptosis. The gastric cancer cells
      (AGS) showed a remarkably higher sensitivity. It seems that several compounds are
      possibly responsible for the cytotoxic effect of the extract.

PMID- 22415323
TI  - Promoter-associated RNAs and promoter-targeted RNAs.
AB  - The world of RNAs is much more complex than previously thought, and has rapidly
      emerged as one of the most actively researched topics in the life sciences.
      Recently, two findings in this field were reported and given special attention:
      promoter-associated RNAs (paRNAs), a novel class of RNAs with numerous potential
      functions; and promoter-targeted RNA-induced transcriptional gene regulation, a
      new regulatory mechanism to control transcription. In this review, we summarize
      the studies in these two areas, and outline the current understanding with
      respect to the potential biological functions of paRNAs, and the molecular
      mechanisms of promoter-targeted RNA-induced transcriptional gene silencing and
      activation. Additionally, we seek to integrate these two areas, as paRNAs may
      have potential biological links with promoter-targeted RNA-induced
      transcriptional gene regulation. Finally, we will discuss the significance of
      identifying paRNAs and the possible use of promoter-targeted RNAs in gene
      regulation and therapy.

PMID- 22415322
TI  - Interkinetic nuclear migration: beyond a hallmark of neurogenesis.
AB  - Interkinetic nuclear migration (INM) is an oscillatory nuclear movement that is
      synchronized with the progression of the cell cycle. The efforts of several
      researchers, following the first report of INM in 1935, have revealed many of the
      molecular mechanisms of this fascinating phenomenon linking the timing of the
      cell cycle and nuclear positioning in tissue. Researchers are now faced with a
      more fundamental question: is INM important for tissue, particularly brain,
      development? In this review, I summarize the current understanding of the
      regulatory mechanisms governing INM, investigations involving several different
      tissues and species, and possible explanations for how nuclear movement affects
      cell-fate determination and tissue formation.

PMID- 22415324
TI  - Chromogranin A binds to alphavbeta6-integrin and promotes wound healing in mice.
AB  - Chromogranin A (CgA), a secretory protein expressed by many neuroendocrine cells,
      neurons, cardiomyocytes, and keratinocytes, is the precursor of various peptides
      that regulate the carbohydrate/lipid metabolism and the cardiovascular system. We
      have found that CgA, locally administered to injured mice, can accelerate
      keratinocyte proliferation and wound healing. This biological activity was
      abolished by the Asp(45)Glu mutation. CgA and its N-terminal fragments, but not
      the corresponding Asp(45)Glu mutants, could selectively recognize the alphavbeta6
      integrin on keratinocytes (a cell-adhesion receptor that is up-regulated during
      wound healing) and regulate keratinocyte adhesion, proliferation, and migration.
      No binding was observed to other integrins such as alphavbeta3, alphavbeta5,
      alphavbeta8, alpha5beta1, alpha1beta1, alpha3beta1, alpha6beta4, alpha6beta7 and
      alpha9beta1. Structure-activity studies showed that the entire CgA(39-63) region
      is crucial for alphavbeta6 recognition (K(i) = 7 nM). This region contains an RGD
      site (residues CgA(43-45)) followed by an amphipathic alpha-helix (residues
      CgA(47-63)), both crucial for binding affinity and selectivity. These results
      suggest that the interaction of the RGD/alpha-helix motif of CgA with alphavbeta6
      regulates keratinocyte physiology in wound healing.

PMID- 22415327
TI  - Reactivity of lithium n-butyl amidinates towards group 14 metal(II) chlorides
      providing series of hetero- and homoleptic tetrylenes.
AB  - The new class of homo- and heteroleptic n-butyl-N,N'-disubstituted amidinato
      group 14 metal(II) complexes were prepared by salt elimination from starting
      lithium amidinates and metal(II) chlorides both in stoichiometric ratio 2:1 and
      1:1, respectively. The target amidinates contain less bulky isopropyl or
      cyclohexyl as well as a sterically demanding aromatic substituent. Desired 1:1
      Pb(II) complexes are not accessible by the described procedure. Ligand transfer
      from Pb to Sn is taking place if homoleptic Pb(II) compounds are reacted with
      SnCl(2). Prepared tetrylenes were characterized by (1)H, (13)C, (119)Sn and
      (207)Pb NMR spectroscopy in C(6)D(6) or THF-d(8). X-Ray diffraction studies of
      one heteroleptic Ge(II) monomeric where the coordination polyhedron of the three
      coordinated germanium atoms is a trigonal pyramid, two different dimeric
      structures of heteroleptic Sn(II) complexes, one amidine hydroiodide byproduct
      and the oxidation product of the heteroleptic chloro Sn(II) amidinate as a
      tetranuclear species with two Sn(IV) and two Sn(II) atoms in central Sn(2)O(2)
      planar ring were performed on appropriate single crystals. The dimer of one of
      the heteroleptic stannylenes reveals a new type of monomeric units connection,
      weak Sn-Cl contact and an interaction of the tin atom with delocalized N-C(C)-N
      system of the amidinato ligand of the second molecule.

PMID- 22415325
TI  - Heterogeneity of molecular markers in chronic myelomonocytic leukemia: a disease
      associated with several gene alterations.
AB  - The relatively homogenous clinical features and poor prognosis of chronic
      myelomonocytic leukemia (CMML) are associated with a molecular heterogeneity,
      with various mutations impacting several convergent pathways. Due to the
      restricted understanding of the mechanism involved in leukemogenesis, CMML still
      appears as a diagnostic and therapeutic undertaking, and poor prognosis of
      leukemia. Contrary to chronic myelogenous leukemia, BCR-ABL1-positive,
      cytogenetic, and molecular abnormalities of CMML are not specific and not
      pathognomonic, confirming the different levels of heterogeneity of this disease.
      Various mutations can be associated with a common phenotype not distinct at the
      clinical level, further demonstrating that molecular probings are needed for
      choosing individual targeted therapies.

PMID- 22415328
TI  - Explaining the erectile responses of rapists to rape stories: the contributions
      of sexual activity, non-consent, and violence with injury.
AB  - In phallometric research, rapists have a unique pattern of erectile responses to
      stimuli depicting sexual activities involving coercion and violence. In this
      study, we attempted to determine the cues that control rapists' erectile
      responses to rape stories in the laboratory. A total of 12 rapists and 14 non
      rapists were exposed to recorded audio scenarios that systematically varied with
      regard to the presence or absence of three orthogonally varied elements: sexual
      activity and nudity, violence and injury, and expression of non-consent. As
      expected from prior research, an index computed by subtracting participants'
      greatest mean responses to stories describing mutually consenting sexual activity
      from their greatest mean responses to stories describing rape was much higher
      among rapists than non-rapists. Both groups showed larger responses when stories
      involved sexual activity and nudity, but neither group exhibited a preference for
      cues of violence and serious injury, or for cues of non-consent. The element that
      produced the larger group difference, however, was the presence or absence of
      active consent. The results indicated that a sexual interest in (or indifference
      to) non-consent is at least as central to accounting for the unique sexual
      orientation of rapists as is sexual responding to violence and injury.

PMID- 22415329
TI  - Attitudes of Cairo University medical students toward smoking:  the need for
      tobacco control programs in medical education.
AB  - BACKGROUND: Tobacco smoking rates are increasing in developing countries and so
      are tobacco-related chronic diseases. Reported figures from the WHO show rates of
      smoking in Egypt as high as 20% but limited information is available about
      smoking specifically among physicians and medical students. MATERIALS AND
      METHODS: Final-year medical students of Cairo University were surveyed regarding
      their tobacco behavior and attitudes using a modified Global Health Professions
      Student Survey. We approached 220 students by randomly selecting clinical units
      into which they were assigned and requested completion of the survey. RESULTS:
      Ever users of some form of tobacco comprised 46.7% of students sampled, current
      users of cigarettes comprised 17.4%, and current users of water pipe 'sheesha'
      comprised 17.6%. The vast majority (87.7%) of students believed that smoking is a
      public health problem in Cairo and supported restriction of tobacco. Yet, only
      58.5% stated that they were taught it is important for physicians to provide
      tobacco education materials to patients. Among ever users of cigarettes, 54.4%
      believed health professionals do not serve as health role models for patients,
      and only a small percentage of all students (34.2%) stated that they had received
      some form of training on smoking cessation in their medical curriculum to be able
      to instruct patients. CONCLUSION AND RECOMMENDATIONS: A high rate of smoking was
      revealed among medical students in Cairo. Overall, approximately 23.4% of
      students were currently smoking cigarettes and/or sheesha, and 46.7% were ever
      users of some form of tobacco. A formal antitobacco program for medical students
      should be incorporated into their medical curriculum to change the attitudes of
      medical students and overcome the anticipated increase in chronic diseases in
      Egypt.

PMID- 22415326
TI  - The cerebrospinal fluid: regulator of neurogenesis, behavior, and beyond.
AB  - The cerebrospinal fluid (CSF) has attracted renewed interest as an active
      signaling milieu that regulates brain development, homeostasis, and disease.
      Advances in proteomics research have enabled an improved characterization of the
      CSF from development through adulthood, and key neurogenic signaling pathways
      that are transmitted via the CSF are now being elucidated. Due to its immediate
      contact with neural stem cells in the developing and adult brain, the CSF's
      ability to swiftly distribute signals across vast distances in the central
      nervous system is opening avenues to novel and exciting therapeutic approaches.
      In this review, we will discuss the development of the choroid plexus-CSF system,
      and review the current literature on how the CSF actively regulates mammalian
      brain development, behavior, and responses to traumatic brain injury.

PMID- 22415330
TI  - Incidence and patterns of injury-related mortality:  a register-based follow-up
      study in Alexandria, Egypt (2000-2010).
AB  - BACKGROUND: Injuries, with their grave social and economic consequences, although
      preventable, are an important cause of death in individuals in their most
      productive earning years, especially in developing countries. This study aimed to
      determine the incidence and describe the patterns of injury-related mortality in
      Alexandria, Egypt, through 2000-2010, and to identify their association with some
      demographic characteristics. MATERIALS AND METHODS: Data were collected from the
      information and decision support center in Alexandria, as case records, for the
      period 2000-2010. STATA 11 software was used. Time-series analyses (trends and
      seasonality) were performed for all injuries combined and separately. The
      association between demographic characteristics and injury-related mortalities
      was determined using zero-inflated Poisson regression. RESULTS: Injury-related
      mortalities comprised a total of 19 731 deaths between 2000 and 2010 (the
      incidence ranged between 38.3/100 000 and 51.1/100,000). Road traffic accident
      was the first leading cause. Almost 70% of injury-related deaths occurred in the
      age group 15 to <60 years. Men were more at risk than women for all types of
      injuries, except burns. Higher rates were calculated for poor and remote
      districts. Summer months showed the highest seasonal index for each type and all
      combined. CONCLUSION AND RECOMMENDATION: Policy makers need to recognize injuries
      as a public health crisis, especially road traffic accidents, and need to design
      and implement urgent interventions for safety applicable to the Egyptian
      demography and distribution.

PMID- 22415331
TI  - Trend, features and outcome of meningitis in the Communicable Diseases hospital,
      Alexandria, Egypt, 1997-2006.
AB  - BACKGROUND: Following vaccine introduction, long-term epidemiological changes
      have been occurred in meningitis. Studying these changes is of practical
      importance for both public health planning and clinical management. OBJECTIVES:
      To study trend in meningitis in Alexandria, Egypt (1997-2006) as well patients'
      characteristics and outcome. MATERIALS AND METHODS: The descriptive epidemiologic
      approach was adopted. Study population was all discharge records and computer
      files of meningitis admissions to the Communicable Diseases Hospital in
      Alexandria, Egypt, 1997-2006. Outcome measures were age, number and percentage of
      patients, organisms proportions and case fatality. RESULTS: The study included
      1210 recorded meningitis cases. Patients had a mean age of 22.26 years and a male
      to female ratio of 1.8 : 1. Study started with a sharp descent of yearly
      admissions (1997-1999) and ended by a sharp increase (2004-2006). Cases
      insignificantly increased during autumn through spring. Neisseria meningitidis
      was the dominant pathogen (28.9%) in all years. Mycobacterium tuberculosis (MTB)
      was the second common agent (11.6%) with a decreasing frequency till 2000.
      Streptococcus pneumoniae was responsible for 8.9% of cases. Group B Streptococci
      and Haemophilus influenzae type b caused 2.8% and 2.4% of cases respectively.
      Both had a declining trend. Other bacteria (gram negative bacteria, non specific
      streptococci and staphylococci) was isolated in 2.7% whereas no organism could be
      identified in 45.6% of specimens. All agent differences were statistically
      significant where P<0.001. The mean hospital stay was 14.95 days. Overall case
      fatality was 17.6%. The most lethal was other bacteria [Odds Ratio=6.0, 95%
      Confidence interval=3.0-12.2]. Fatal outcome was predicted by short hospital stay
      (regression coefficient(r)=-0.17, P<0.001), diagnosis of other bacterial (r=1.75,
      P<0.001), pneumococcal (r=0.66, P=0.02) or tuberculous meningitis (r=0.59,
      P=0.04) and being an elderly (r=1.80, P<0.001) or an adult (r=1.03, P<0.001).
      CONCLUSION: Neisseria remained the main etiologic agent of meningitis. TB emerged
      as the second pathogen. Rate of bacterial un-detection was high. Mean age of
      meningitis had shifted to adult age. Other bacteria, pneumococci, MTB and
      advanced age were important predictors for mortality.

PMID- 22415332
TI  - General practitioners' knowledge and practices related to alopecia areata in
      Qassim region, Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVES: The importance of alopecia areata (AA) originated from
      the social acceptance of its psychological and emotional consequences. This study
      aimed to explore the knowledge and practices of general practitioners regarding
      the disease in Qassim region, Saudi Arabia, to obtain baseline data to aid in
      quality improvement of the available health services. SUBJECTS AND METHODS: The
      study included 142 general practitioners working in primary healthcare centers in
      the Qassim region. Knowledge on causes, risk factors, and treatment practices was
      obtained using a self-administrated structured questionnaire. RESULTS: The mean
      (+/- SD) age of participants was 42.9 +/- 7.8 years. More than 35.0% of them had
      work experience of less than 10 years. Nineteen percent of the participants had
      low knowledge score, with significant difference in sex and years of work
      experience. Approximately 45.8% of surveyed doctors reported AA to be an
      autoimmune disease, 68.3% incorrectly responded that AA is more common in male
      patients, 64.1% recognized that family history is important, 26.1% blamed
      personal hygiene, and 16.2% thought that AA is a communicable disease. With
      regard to management, 45.7% of participants prescribed local steroids for
      treatment; however, 25.3% prescribed only multivitamins. CONCLUSION AND
      RECOMMENDATIONS: That general practitioners in the Qassim region have
      satisfactory knowledge of AA, and most of them engage in fair treatment
      practices. However, there are still some gaps in different aspects that warrant
      continuous educational programs to improve their quality and performance.

PMID- 22415333
TI  - Famotidine in the treatment of functional dyspepsia:  a randomized double-blind,
      placebo-controlled trial.
AB  - AIM: In the present study, we aimed to investigate patients with a documented
      diagnosis of functional dyspepsia (FD) who had been admitted to our outpatient
      Gastroenterology Clinic and provided consent to participate in this randomized,
      double-blind, placebo-controlled trial of the therapeutic impact of famotidine on
      the symptoms and quality of life of FD patients. PARTICIPANTS AND METHODS: A
      total of 160 patients attending our outpatient clinic with a diagnosis of FD
      according to Rome III criteria were enrolled in this double-blind study. They
      were randomized into case (famotidine treatment) and placebo groups; patients
      were asked to refill the Honk Kong dyspepsia index (a self global assessment
      tool) before the start of the study as well as after 3 months of treatment.
      RESULTS: Both famotidine and placebo led to significant improvements in dyspepsia
      symptoms, except for vomiting in both groups and loss of appetite in the placebo
      control group. However, the extent of these improvements was not different
      between the two study groups for most of the study parameters, whereas belching,
      feeling of acid regurgitation, heartburn, and the total score for the Hong Kong
      dyspepsia index were significantly more responsive to famotidine than placebo. No
      significant effectiveness of famotidine therapy was found regarding quality of
      life. CONCLUSION AND RECOMMENDATIONS: This study showed a significant improvement
      in the total dyspepsia scores of FD, with a marked effect on belching, heartburn,
      and the feeling of acid regurgitation. These findings suggest that famotidine may
      be administered in certain FD patients who have significantly more symptoms of
      belching, heartburn, and acid regurgitation.

PMID- 22415334
TI  - Pediatric burns in Khuzestan Province, Iran.
AB  - BACKGROUND: Burn injuries are the most frequently occurring injuries among
      pediatric populations worldwide, and they are significant pediatric injuries in
      Iran. AIM: This study was conducted to analyze the pattern of pediatric burns in
      Khuzestan province in the south-west of Iran from April 2006 to March 2007.
      PATIENTS AND METHODS: The location of the study was Taleghani Hospital, a sole
      center for burn patients in Khuzestan province. The number of patients with burns
      admitted to the center in 1 year (from April 2006 to March 2007) was 211. Data
      were obtained by reviewing the medical records of patients hospitalized at the
      center. RESULTS: Of the patients, 85 (40.3%) were female and 126 (59.7%) were
      male. Of the 85 female patients, 50 were from urban areas and 35 were from rural
      areas. Of the 126 male patients, 68 (54%) were from urban areas and 58 (46%) were
      from rural areas. The mean +/- SE age of the children ranging between 0 and 11
      years was 3.20 +/- 0.188. Scalding was the predominant cause of burns and caused
      86.7% of the burns. The age of the patients with scald injuries (2.95 +/- 2.56
      years) was significantly lower than that of patients with flame injuries (4.28 +/
      3.3 years) (P=0.007). Correlation analysis showed that younger children and
      urban residents are more vulnerable to scald injuries. The mean body surface area
      of burns was 20.5 +/- 10.26 cm in all patients. CONCLUSION AND RECOMMENDATIONS:
      Scalding was the most common cause of burns. Age <4 years and residency in urban
      areas were the major factors increasing the risk of burn accidents in children in
      Khuzestan. An appropriate burn prevention program, with focus on education, is
      needed to prevent this injury.

PMID- 22415335
TI  - Comparison of vitamin D deficiency in Saudi married couples.
AB  - BACKGROUND/OBJECTIVE: Vitamin D deficiency is highly prevalent in Saudi Arabia.
      The study objective was to compare vitamin D deficiency in Saudi married couples.
      SUBJECTS/METHODS: This cross-sectional study was carried out in the Royal Guard
      primary health care center in Riyadh, Saudi Arabia on a consecutive sample of 50
      Saudi married couples attending the center without complaints related to vitamin
      D deficiency. Data were collected through an interview questionnaire addressing
      the risk factors and dietary habits. Quantitative determination of total 25
      hydroxy vitamin D in blood was done by Electro-Chemical Luminescence assay.
      Fieldwork was carried out from December 2010 to January 2011. RESULTS: Men had
      higher sun exposure (P = 0.001), more use of light clothes at home (P = 0.002)
      and more intake of milk (P = 0.023) and soft drinks (P = 0.001). Vitamin D was
      higher in men with mean difference about 9 nmol/l (P < 0.001). The prevalence of
      vitamin D deficiency (<25 nmol/l) was 70% in women, compared with 40% in men (P =
      0.001). Multivariate analysis identified male gender, physical activity and the
      intake of milk as statistically significant positive independent predictors of
      vitamin D level, adjusted for factors as age, sun exposure, clothing, skin color,
      BMI, soft drinks and animal protein intake. CONCLUSION: Vitamin D deficiency is
      very high among Saudi married couples, especially wives. Female gender is an
      independent predictor of lower vitamin D level, in addition to sedentary
      lifestyle and low milk consumption. There is a need to revise the levels set for
      the diagnosis of vitamin D deficiency or insufficiency in the study region.

PMID- 22415336
TI  - Dietary associations with prediabetic states--the DR's EXTRA Study
      (ISRCTN45977199).
AB  - BACKGROUND/OBJECTIVES: Impaired fasting plasma glucose (IFG) and impaired glucose
      tolerance (IGT) predict development of type 2 diabetes (T2D), but display
      different pathophysiology for T2D. We studied the association of selected food
      items and nutrients with IFG, IGT and combined IFG and IGT (IFG+IGT), independent
      of cardiorespiratory fitness (VO(2max)). SUBJECTS/METHODS: In a population-based
      sample of 1261 individuals, aged 58-78 years, we identified 126 subjects with
      IFG, 97 with IGT and 49 with simultaneous IFG and IGT by an oral glucose
      tolerance test. Dietary intake was assessed by 4-day food records.
      Cardiorespiratory fitness was assessed by defining maximal oxygen uptake
      (VO(2max)) from respiratory gas analysis during a maximal symptom-limited
      exercise stress test on a bicycle ergometer. RESULTS: Increased intake of
      saturated fat was associated with higher odds for IFG (OR 1.07; 1.01-1.14) after
      adjustment for age, gender, VO(2max) and energy misreporting variable.
      Consumption of additional whole-grain bread (50 g/1000 kcal) and intake of
      dietary fiber (g/1000 kcal) were inversely associated with IGT (OR 0.61; 0.41
      0.92, OR 0.91; CI 0.85-0.97, respectively). CONCLUSION: Dietary fiber and sources
      of cereal fiber are negatively associated with IGT, and saturated fat intake is
      positively associated with IFG, but not with IGT. The present data give practical
      dietary means at the population level for the elimination of prediabetic
      conditions.

PMID- 22415337
TI  - Vitamin D status and determinants of deficiency among non-pregnant Jordanian
      women of reproductive age.
AB  - BACKGROUND/OBJECTIVES: Vitamin D deficiency, a risk factor for osteomalacia and
      osteoporosis, is a re-emerging health problem globally. While sunlight is an
      important vitamin D source, previous investigations among women whose culture
      encourages skin covering have been small, not nationally representative, or both.
      We investigated serum 25-hydroxyvitamin D (25(OH)D(3)) status and factors
      associated with deficiency in a nationally representative survey of 2013
      Jordanian women of reproductive age in Spring 2010. SUBJECTS/METHODS: We measured
      25(OH)D(3) concentrations by liquid chromatography-tandem mass spectrometry and
      calculated prevalence ratios for deficiency associated with skin covering and
      other factors. RESULTS: Results showed 60.3% (95% CI: 57.1-63.4%) deficiency (<12
      ng/ml) and 95.7% (95% CI: 94.4-96.8%) insufficiency (<20 ng/ml) among women.
      Prevalence of deficiency was 1.60 times higher for women who covered with a
      scarf/hijab (95% CI: 1.06-2.40, P = 0.024) and 1.87 times higher for women who
      wore full cover, or a niqab (95% CI: 1.20-2.93, P = 0.006), compared with the
      women who did not wear a scarf/hijab or niqab. Compared with rural women
      completing at least secondary education, prevalence of deficiency was 1.30 times
      higher for urban women of the same education level (95% CI: 1.08-1.57, P =
      0.006), 1.18 times higher for urban women completing less than secondary
      education (95% CI: 0.98-1.43, P = 0.09), and 0.66 times lower for rural women
      completing less than secondary education (95% CI: 0.52-0.84, P = 0.001).
      CONCLUSION: Vitamin D deficiency and insufficiency pose significant public health
      problems in Jordanian women. Prevalence of deficiency is significantly higher
      among urban women and among women who cover with a scarf/hijab or niqab.

PMID- 22415338
TI  - Spin crossover transition of Fe(phen)2(NCS)2: periodic dispersion-corrected
      density-functional study.
AB  - Periodic dispersion corrected DFT calculations have been performed to study the
      spin-crossover transition of Fe(phen)(2)(NCS)(2) in the molecular and in the
      crystalline state. We show that London dispersion interactions play a crucial
      role in the cohesion of the crystals. Based on calculations of vibrational
      eigenstates of the isolated molecule and of the crystalline phase in both the low
      and high-spin states, the transition entropies and enthalpies have been
      calculated. We demonstrate that, due to the stabilization of the low-spin state
      by intermolecular dispersion forces, the transition enthalpy at the transition
      temperature is larger for the crystalline phase in comparison with an isolated
      molecule. The effective coordination number of the nitrogen atoms of the ligands
      around the iron atom has been identified as the order parameter driving the quasi
      reversible low-spin to high-spin transition in the crystal. Finally, using
      constrained geometry relaxations at fixed values of the coordination number, we
      computed the energy barrier of the LS to HS transition and found it to be in a
      reasonable agreement with the experimental value.

PMID- 22415339
TI  - Human skin permeation of neutral species and ionic species: extended linear free
      energy relationship analyses.
AB  - The permeability, K(p), of some ionized solutes (including nine acids and nine
      bases) through human epidermis membrane was measured in this work. Combined with
      the experimental K(p) data set for neutral species created by Abraham and Martins
      and reliable K(p) data for ionic species from the literature, a linear free
      energy relationship (LFER) analysis was conducted. The values of log K(p) for 118
      compounds have been correlated with solute descriptors to yield an LFER equation
      that incorporates neutral species and ionic species, with R(2) = 0.861 and SD =
      0.462 log units. The equation can be used to predict K(p) for neutral species and
      ionic species, as well as partly ionized solutes. Predicted values for the
      passive permeation of the sodium ion and the tetraethylammonium ion are in good
      accord with the experimental values. It was observed that neutral acids and bases
      are more permeable than their ionized forms, and that the ratio depends on the
      actual structure. The correlation between human skin permeation and water-organic
      solvent/artificial membrane partitions was investigated by comparison of the
      coefficients in the LFER equations. Partition into cerasome is a reasonable model
      for partition into skin, and using cerasome as a surrogate for the partitioning
      process, we separate permeation into partition and diffusion processes. We show
      that the poor permeability of ionic species is largely due to slow diffusion
      through the stratum corneum. This is especially marked for a number of protonated
      base cations.

PMID- 22415340
TI  - Alveolar echinococcosis of the liver: a single center experience.
AB  - INTRODUCTION: In humans, alveolar echinococcosis (AE) of the liver is caused by
      canine tapeworm called Echinococcus multilocularis. The disease is most prevalent
      in the northern hemisphere and in the eastern part of Turkey. OBJECTIVES: The aim
      of the study was to review the natural history of AE and its clinical and
      radiological features. PATIENTS AND METHODS: The retrospective study involved 23
      patients (10 men, 13 women), aged 34-75 years with AE who had been referred to
      our liver disease clinic in the past 4 years. Only patients with pathologically
      proven AE were included in the study. The sociodemographic, clinical, and
      radiological features of AE were also evaluated. RESULTS: The main laboratory
      characteristics of AE included mild eosinophilic leukocytosis with
      hypergammaglobulinemia, elevated C-reactive protein levels, near-normal liver
      transaminases, and increased levels of cholestatic enzymes and immunoglobulin E.
      Eight patients (35%) had hepatitis B e antigen-negative hepatitis B infection.
      Budd-Chiari syndrome was identified in 3 of 23 patients (13%). Eighty-three
      percent of the patients had a seropositive test result for AE, and approximately
      one-third of the patients had distant metastasis. Surgical treatment was
      administered in 4 patients. Four patients died due to complications during follow
      up. CONCLUSIONS: Patients with AE have numerous complications and advanced
      disease at the time of diagnosis. The clinical picture of AE comprises a number
      of hepatic and extrahepatic disturbances related both to destructive and mass
      effects of the tapeworm.

PMID- 22415341
TI  - The rehabilitation of children with anti-N-methyl-D-aspartate-receptor
      encephalitis: a case series.
AB  - Anti-N-methyl-D-aspartate (NMDA)-receptor encephalitis is a serious, complex, and
      potentially fatal disease in children. Children with this condition frequently
      present with altered mental status, rapid functional deterioration, and seizures.
      Despite aggressive treatment with immune therapy such as corticosteroids,
      intravenous immunoglobin, and plasmapheresis, children often need extensive
      rehabilitative services and can be left with lasting deficits. In this case
      series, we report on six known consecutive pediatric cases of N-methyl-D
      aspartate-receptor antibody encephalitis in Northern California requiring
      comprehensive inpatient rehabilitation. The children presented with a variety of
      symptoms and had waxing and waning clinical courses. All children progressed well
      through their rehabilitation programs but were discharged home with persistent
      functional deficits. At follow-up, all but one child had lasting deficits.
      Because of the complicated management and extensive rehabilitation needs of
      children with anti-N-methyl-D-aspartate-receptor encephalitis, physiatrists and
      other rehabilitation providers should be knowledgeable about this complex
      condition.

PMID- 22415342
TI  - Do current methods of strength testing for the return to sport after injuries
      really address functional performance?

PMID- 22415344
TI  - Cerebrotendinous xanthomatosis with progressive cerebellar vacuolation : six-year
      MRI follow-up.

PMID- 22415343
TI  - The role of intraoperative micro-Doppler ultrasound in verifying proper clip
      placement in intracranial aneurysm surgery.
AB  - INTRODUCTION: Aneurysmal subarachnoid hemorrhage constitutes a clinical entity
      associated with high mortality and morbidity. It is widely accepted that improper
      clip placement may have as a result of incomplete aneurysm occlusion and/or
      partial or complete obstruction of an adjacent vessel. Various modalities,
      including intraoperative or postoperative digital subtracting angiography, near
      infrared indocyanine green angiography, micro-Doppler ultrasonography (MDU), and
      neurophysiological studies, have been utilized for verifying proper clip
      placement. The aim of our study was to review the role of MDU during aneurysmal
      surgery. METHODS: A literature search was performed using any possible
      combination of the following terms: "aneurysm," "brain," "cerebral," "clip,"
      "clipping," "clip malpositioning," "clip repositioning," "clip suboptimal
      positioning," "Doppler," "intracranial," "microsurgery," "micro-Doppler,"
      "residual neck," "ultrasonography," "ultrasound," and "vessel occlusion".
      Additionally, reference lists from the retrieved articles were reviewed for
      identifying any additional articles. Case reports and miniseries were excluded.
      RESULTS: A total of 19 series employing intraoperative MDU during aneurysmal
      microsurgery were retrieved. All studies demonstrated that MDU accuracy is
      extremely high. The highest reported false-positive rate of MDU was 2 %, while
      the false-negative rate was reported as high as 1.6 %. It has been demonstrated
      that the presence of subarachnoid hemorrhage, specific anatomic locations, and
      large size may predispose to improper clip placement. Intraoperative MDU's
      technical limitations and weaknesses are adequately identified, in order to
      minimize the possibility of any misinterpretations. CONCLUSION: Intraoperative
      MDU constitutes a safe, accurate, and low cost imaging modality for evaluating
      blood flow and for verifying proper clip placement during microsurgical clipping.

PMID- 22415346
TI  - Hypertension resulting from overexpression of translationally controlled tumor
      protein increases the severity of atherosclerosis in apolipoprotein E knock-out
      mice.
AB  - Hypertension is a well-established etiological factor for atherogenesis. We
      previously showed that transgenic mice overexpressing translationally controlled
      tumor protein (TCTP) develop systemic arterial hypertension. In this study we
      explored the cardiovascular effects of TCTP overexpression and possibly of the
      resultant hypertension on the severity of atherosclerosis in apolipoprotein E
      deficient mice. Through multiple mating of TCTP-overexpressing transgenic mice
      (TCTP-TG) with apolipoprotein E knock-out mice (ApoE KO), we generated non
      transgenic (nTG), TCTP-TG, nTG/ApoE KO and TCTP-TG/ApoE KO mice with similar
      genetic background. Male mice, 7-week old, were fed a lipid-enriched Western diet
      for 16 weeks, and blood pressure and body weight change were monitored every 2
      weeks. Plasma lipid profiles and atherosclerotic lesions in aorta were quantified
      at the end of study. We found that blood pressure levels of TCTP-TG and TCTP
      TG/ApoE KO, were similarly elevated while nTG and nTG/ApoE KO mice were
      normotensive. TCTP overexpression in ApoE KO mice led to significant exacerbation
      of atherosclerotic lesions. Feeding Western diet resulted in increases in total
      cholesterol, triglyceride (TG) and low density lipoprotein, and decreased high
      density lipoprotein (HDL) in ApoE KO mice. No significant differences were found
      in plasma lipid profiles of nTG/ApoE KO and TCTP-TG/ApoE KO. This study suggests
      that overexpression of TCTP, which induces hypertension, also accelerates the
      development of atherosclerotic lesion caused by high-fat and high-cholesterol
      diet without significantly altering plasma lipid profiles. We conclude that TCTP
      induced hypertension could increase the severity of atherosclerotic lesion and
      suggest that inhibition of TCTP or its signaling pathways may be a potential
      approach to the therapy of both diseases, hypertension and atherosclerosis.

PMID- 22415347
TI  - Nanoinjection: pronuclear DNA delivery using a charged lance.
AB  - We present a non-fluidic pronuclear injection method using a silicon microchip
      "nanoinjector" composed of a microelectromechanical system with a solid,
      electrically conductive lance. Unlike microinjection which uses fluid delivery of
      DNA, nanoinjection electrically accumulates DNA on the lance, the DNA-coated
      lance is inserted into the pronucleus, and DNA is electrically released. We
      compared nanoinjection and microinjection side-by-side over the course of 4 days,
      injecting 1,013 eggs between the two groups. Nanoinjected zygotes had
      significantly higher rates of integration per injected embryo, with 6.2%
      integration for nanoinjected embryos compared to 1.6% integration for
      microinjected embryos. This advantage is explained by nanoinjected zygotes'
      significantly higher viability in two stages of development: zygote progress to
      two-cell stage, and progress from two-cell stage embryos to birth. We observed
      that 77.6% of nanoinjected zygotes proceeded to two-cell stage compared to 54.7%
      of microinjected zygotes. Of the healthy two-cell stage embryos, 52.4% from the
      nanoinjection group and 23.9% from the microinjected group developed into pups.
      Structural advantages of the nanoinjector are likely to contribute to the high
      viability observed. For instance, because charge is used to retain and release
      DNA, extracellular fluid is not injected into the pronucleus and the cross
      sectional area of the nanoinjection lance (0.06 um(2)) is smaller than that of a
      microinjection pipette tip (0.78 um(2)). According to results from the
      comparative nanoinjection versus microinjection study, we conclude that
      nanoinjection is a viable method of pronuclear DNA transfer which presents
      viability advantages over microinjection.

PMID- 22415348
TI  - Genetics of thoracic aortic aneurysms.
AB  - Understanding of the genetics of thoracic aortic aneurysm is increasing rapidly,
      due to discovery of novel genes, better definition of the phenotypes associated
      with mutations in a given gene and better understanding of the pathophysiology.
      Beyond Marfan syndrome, usually related to mutation in FBN1, mutations have been
      reported in TGFBR1, TGFBR2, ACTA2, MYH11, and SMAD3. All are transmitted as
      dominant autosomal traits. The importance of genetics in patients with bicuspid
      aortic valve and non-syndromic thoracic aortic aneurysm is also increasingly
      recognized. The following is a review of the phenotypes associated with the
      different mutations and the clinical consequences of this recent information.

PMID- 22415349
TI  - Tracking of wisent-bison-yak mitochondrial evolution.
AB  - One of the most informative sources which allow the drawing of far-reaching
      conclusions about the origins and phylogenetics of many species, including
      domestic animals and humans, is mitochondrial DNA (mtDNA). One of the important
      research targets should include the identification of similarities between wild
      and domestic species. The analysis involved the nucleotide sequences of mtDNA of
      wisent, auroch, bison, yak, bovine reference sequence (BRS) T3, T3a, T3b, T1,
      T1a, T1'2'3, T2, T3, T4, T5, Q, Q1, P, R, I1, and I2 bovine haplotypes. The non
      coding D-loop regions were excluded from the evolutionary analysis and 15,419-bp
      coding sequences were used in the final dataset. Trees constructed on the basis
      of whole mitochondrial genomes or on total mtDNA coding sequences alignment were
      generally in agreement with previous studies on the Bovini tribe. American bison
      shows stronger maternal relationships to yak than to wisent. It seems that the
      isolation and divergence of wisent took place early, almost 2 to 1.6 million
      years ago. This appears to be compatible with the paleontological date,
      indicating Late Pleistocene speciation of Bison bonasus. The yak/bison
      mitochondrial transfer model is in agreement with our mutation analysis and
      phylogenetic tree. The bison/yak mutations were collected in the bison
      mitochondrial genome before the transfer. After the transfer, the parallel
      accumulation of unique mutations took place. According to our assessment, the
      transfer took place at about 700 ky. The characteristic feature of the wisent and
      bison evolution is the maintenance of mtDNA variability, despite the fact that
      both species underwent population bottlenecks. Our studies did not reveal any
      impact of these phenomena populations in the analyzed mitochondrial genomes.

PMID- 22415350
TI  - Novel insertion in exon 5 of the TCOF1 gene in twin sisters with Treacher Collins
      syndrome.
AB  - Treacher Collins syndrome (TCS) is associated with an abnormal differentiation of
      the first and second pharyngeal arches during fetal development. This causes
      mostly craniofacial deformities, which require numerous corrective surgeries. TCS
      is an autosomal dominant disorder and it occurs in the general population at a
      frequency of 1 in 50,000 live births. The syndrome is caused by mutations in the
      TCOF1 gene, which encodes the serine/alanine-rich protein named Treacle. Over 120
      mutations of the TCOF1 gene responsible for TCS have been described. About 70% of
      recognized mutations are deletions, which lead to a frame shift, formation of a
      termination codon, and shortening of the protein product of the gene. Herewith, a
      new heterozygotic insertion, c.484_668ins185bp, was described in two monozygotic
      twin sisters suffering from TCS. This mutation was absent in their father,
      brother, and uncle, indicating a de novo origin. The insertion causes a shift in
      the reading frame and premature termination of translation at 167 aa. The novel
      insertion is the longest ever found in the TCOF1 gene and the only one found
      among monozygotic twin sisters.

PMID- 22415351
TI  - Chromosome fragility in river buffalo cows exposed to dioxins.
AB  - Fifty river buffalo (Bubalus bubalis, 2n = 50) cows reared in two different
      provinces of Campania (southern Italy) underwent cytogenetic investigations to
      ascertain possible differences in their chromosome stability. One group (Caserta
      province) was under legal sequestration due to the presence in the milk mass of
      higher mean values of dioxins [21.79 pg/g of fat as sum of polychloro-dibenzo
      dioxins (PCDDs), polychloro-dibenzo-furans (PCDFs) and dioxin-like
      polychlorobiphenyls (DL-PCBs)] than both those permitted (6.0 pg/g of fat as WHO
      TEQ) and those (1.3 pg/g of fat as WHO-TEQ) observed in the control group raised
      in Salerno province. Two types of peripheral blood cell cultures were performed:
      without (normal cultures for the chromosome abnormality (CA) test: chromatid
      breaks, chromosome breaks, fragments) and with the addition of BrdU for the
      sister chromatid exchange (SCE) test). The CA test revealed a significantly (P <
      0.01) higher chromosome fragility in the exposed cows compared to the control.
      Indeed, mean values of CA/cell were 1.26 +/- 1.15 in exposed cows and 0.37 +/-
      0.71 in the control. Mean SCE was higher in exposed cows (8.50 +/- 3.35) than
      that (8.29 +/- 3.51) found in the control but the difference was not significant.
      Comparison within the same group of cows at first (FL) and multiple (ML)
      lactations revealed significantly (P < 0.01) higher mean values of CA/cell in
      exposed ML-cows vs FL-cows while no statistical differences were found between ML
      cows and FL-cows in the control farm. By contrast, significantly (P < 0.01)
      higher mean values of SCE were found in both groups of FL-cows versus ML-cows.
      Comparisons with other previous studied species (sheep and cattle) were also
      performed.

PMID- 22415352
TI  - Expression of the newly identified gene CAC1 in the hippocampus of Alzheimer's
      disease patients.
AB  - Alzheimer's disease (AD), the most common form of senile dementia, is associated
      with neurodegeneration. The development of Alzheimer's disease is related to
      abnormalities of cell cycle regulation. Preliminary work showed that a novel
      gene, CAC1, was highly expressed in tumors and had an oncogene-like function
      related to cell cycle regulation. The pathogenesis of AD is still incompletely
      understood. In this study, we measured the expression level of CAC1 in the
      hippocampus of AD patients to explore the involvement of CAC1 in the development
      of AD. Our findings showed that the expression level of CAC1 in the hippocampus
      of AD patients was significantly lower than that of normal controls. The
      reduction of CAC1 expression did not affect tau/p-tau-396, amyloid precursor
      protein or apolipoprotein E4 in the in vitro model. A reduction of cyclin E was
      detected after a CAC1-knockdown. Interestingly, we found that the knockdown of
      CAC1 by RNAi led to an increase in oxidative stress and the level of p53 protein
      in SHSY-5Y cells. The expression of CAC1 in SHSY-5Y cells protected the cells
      from apoptosis induced by Abeta toxicity or oxidative stress. These results
      established that CAC1 is an important factor for the protection of cells against
      Abeta toxicity and oxidative stress.

PMID- 22415353
TI  - Artificial cold wave-induced cerebral infarction in rats with carotid
      atherosclerosis.
AB  - To investigate the effects of cold on blood pressure, serum endothelin-1 content,
      serum nitric oxide content, and morbidity of cerebral infarction, as well as
      assess the therapeutic effect of nimodipine. A total of 200 rats were initially
      assigned to a normal group (n = 10), sham group (n = 10), and carotid
      atherosclerosis group (n = 180), and subsequently the animals in the carotid
      atherosclerosis group were randomly assigned to three groups: non-cold (n = 59),
      cold treatment (n = 58), and nimodipine (n = 58). Rats in the cold and nimodipine
      groups experienced an artificial cold wave. The temperature was set at 22 degrees
      C for 12 h (7:00 am to 7:00 pm) and then at 4 degrees C for another 12 h (7:00 pm
      to 7:00 am), representing a cycle. The animals underwent three cycles of cold.
      Rats in the nimodipine group were treated with nimodipine and those in the cold
      group with given an equal volume of intragastric normal saline for 3 days.
      Hematoxylin and eosin staining showed features of carotid atherosclerosis in all
      animals. Blood pressure fluctuated with alteration of temperature. A temperature
      decrease was accompanied by an increase of blood pressure and elevation of serum
      levels of endothelium-1 and nitric oxide. In addition, although nimodipine could
      prevent the cold-induced increase of blood pressure and elevation of serum
      endothelium-1 and nitric oxide levels, it had no effect on blood pressure
      fluctuation or morbidity of cerebral infarction. The results suggest that
      dramatic variation in temperature is one of the main causes of cold-induced
      fluctuation of blood pressure.

PMID- 22415354
TI  - The functional role of chromogranins in exocytosis.
AB  - Chromogranins A (CgA) and B (CgB) are the main soluble proteins of large dense
      core secretory vesicles (LDCVs). Using CgA- and CgB-knockout (KO) mice, we found
      that the absence of chromogranins A and B induces significant changes in
      catecholamine (CA) accumulation and the kinetics of exocytosis. By crossing these
      two knockout strains, we generated a viable and fertile double CgA/B-KO mouse in
      which the catecholamine content in chromaffin LDCVs was halved, and the secretory
      response significantly reduced. Incubating cells with L-DOPA increased the
      vesicular CA content in wild-type (WT) but not in Cg-KO cells, which was not due
      to changes in amine transport, or in the synthesis or degradation of cytosolic
      amines. Electron microscopy revealed the presence of giant secretory vesicles
      exhibiting significant alterations, with little or no electrodense inner matrix.
      Proteomic analysis confirmed the absence of CgA and B, and revealed small changes
      in SgII in the LDCV-enriched fraction, as well as the overexpression of
      fibrinogen and other proteins. In summary, our findings indicate that the
      mechanisms responsible for vesicular accumulation of CA are saturated in Cgs-KO
      cells, in contrast to the ample capacity for further accumulation in WT cells. We
      conclude that Cgs contribute to a highly efficient system that directly mediates
      monoamine accumulation and exocytosis in LDCVs.

PMID- 22415355
TI  - Neuroprotective effect of quercetin against hydrogen peroxide-induced oxidative
      injury in P19 neurons.
AB  - Oxidative stress is implicated in neuronal death in a variety of
      neurodegenerative diseases. In the present study, P19 neurons obtained by the
      differentiation procedure from mouse teratocarcinoma P19 cells were used to
      investigate the ability of quercetin, a plant-derived flavonoid, to prevent
      neuronal death induced by exposure to 150 MUM or 1.5 mM hydrogen peroxide
      (H(2)O(2)) for 24 h. Quercetin treatment improved viability of P19 neurons
      exposed to both types of oxidative injury. During the modest oxidative stress,
      quercetin diminished generation of reactive oxygen species (ROS) and prevented
      H(2)O(2)-induced nuclear condensation, increase in caspase 3/7 activity and rise
      in poly(APD-ribose) polymerase expression. Expression of Bcl-2 family members Bax
      and Bcl-2 was not affected by quercetin treatment at both the transcriptional and
      translational levels. During the severe oxidative injury, quercetin prevented
      H(2)O(2)-induced rise in ROS accumulation and changes in plasma membrane
      integrity and nuclear morphology. The obtained results suggest that
      neuroprotective effects of quercetin are related to its antioxidative action and
      prevention of events associated with programmed cell death cascade. In the light
      of these findings, one might assume beneficial effects of quercetin for the
      prevention of oxidative stress-driven neuronal loss in human aging and age
      related neurodegenerative diseases.

PMID- 22415356
TI  - De novo MGC4607 gene heterozygous missense variants in a child with multiple
      cerebral cavernous malformations.
AB  - Cavernous malformations are angiographically occult, low-pressure neurovascular
      lesions with distinct imaging and clinical characteristics; main clinical
      manifestations are seizure, focal neurological deficits and epileptic attacks.
      Here we describe the molecular characterization of an Italian child, a
      symptomatic patient, affected by multiple cerebral cavernous malformations,
      without a family history of the disease and harbouring a new MGC4607 gene
      mutation. We identified two de novo missense variants in exon 6 of the gene both
      present on the same allele (cis configuration). DNA analysis for KRIT1, and
      PDCD10 gene variation through direct sequencing and MLPA analysis excluded
      further mutations. STR multiplex assay, allele-specific analysis and DHPLC
      analysis were performed for a better genetic characterization. Our findings
      emphasize the importance of the genetic test in subjects presenting multiple
      cerebral cavernomas for an adequate counselling, as well as for disease
      management since early identification of genetic abnormalities enable patients to
      have their lesions removed before they haemorrhage and cause deficit and/or
      epilepsy.

PMID- 22415357
TI  - Correlation between oocyte number and follicular fluid concentration of pituitary
      adenylate cyclase-activating polypeptide (PACAP) in women after superovulation
      treatment.
AB  - Follicular growth, ovulation, and luteinization are influenced by interactions of
      peptide and steroid hormone-signaling cascades in the ovary. Pituitary adenylate
      cyclase-activating polypeptide (PACAP) plays an important role in the regulation
      of several endocrine processes and is present in ovarian follicular fluid (FF).
      However, little is known about PACAP in FF with regard to maturation, ovulation,
      fertilization, and successful pregnancy. The aim of this pilot study was to
      investigate whether there is a correlation between PACAP concentration in FF and
      ovarian response to superovulation treatment in infertile women, performed in
      volunteers (n = 132; aged between 20 and 35). After treatment, the number of
      harvested oocytes was recorded and PACAP immunoreactivity in FF was measured by
      radioimmunoassay. All the corresponding PACAP concentrations were below 290
      fmol/ml in cases when the number of harvested oocytes exceeded 14 per patient,
      while in all cases above 290 fmol/ml, the number of oocytes was below 14. Using
      these cutoff values, we determined three study groups: high-PACAP concentration,
      high-oocyte number, and low-PACAP concentration-low-oocyte number groups. Median
      values of PACAP concentration in these groups were 411.2, 106.5, and 101.0
      fmol/ml, respectively, while the median values of harvested oocytes were 5.5,
      19.0, and 5.0, respectively. Differences were significant, indicating a
      correlation between concentration of PACAP in FF and the number of recruited
      oocytes. Higher concentrations of PACAP in FF might be associated with lower
      number of developing oocytes, while low concentrations of PACAP might correlate
      with a markedly higher number of ova retrieved, thus predicting a higher chance
      for ovarian hyperstimulation. Our present study is among the first few human
      clinical studies with direct conclusions drawn for possible clinical impact of
      PACAP.

PMID- 22415358
TI  - Assessing the reliability and validity of a shorter walk test compared with the
      10-Meter Walk Test for measurements of gait speed in healthy, older adults.
AB  - BACKGROUND AND PURPOSE: Walking speed is associated with several health-related
      outcomes. Research examining how differences in test walking distance affect
      walking speed reliability and validity is limited. The primary purpose of this
      study was to examine the reliability and concurrent validity of gait speed
      measurements obtained from a 4-Meter Walk Test compared with the commonly used 10
      Meter Walk Test. A second objective was to similarly examine 2 different timing
      methods: stopwatch and automatic timers. METHODS: Forty-three healthy, older
      adults (mean age = 84.3 +/- 6.9 years) performed 3 consecutive walking trials on
      the 4- and 10-Meter Walk Tests at their self-selected walking speed. RESULTS:
      Gait speed measurements for both tests were shown to have excellent test-retest
      reliability (ICC values of 0.96-0.98), with similar results for stopwatch and
      automatic timer assessments (ICC values of 0.99-1.00). Standard error of the
      measurement (SEM) values were small (0.004-0.008 m/s) across measurement methods.
      While the ICC value for gait speed measurements between the 2 walk tests was
      0.93, the Bland-Altman analysis revealed a discrepancy of +/-0.15 to +/-0.17 m/s
      between measurement methods. DISCUSSION: Both 4- and 10-m gait speed assessments
      had excellent test-retest reliability with similar SEM and minimal detectable
      change values. There was little difference in SEM values between the 2 timing
      methods. While the mean difference in gait speed between the 4- and 10-Meter Walk
      Tests was small, the range of the measurement differences was large enough to
      potentially mask meaningful changes in gait speed over time if both methods were
      used interchangeably. CONCLUSIONS: While the reliability of both walking tests is
      excellent, the 4-Meter Walk Test does not exhibit a high enough degree of
      concurrent validity with the 10-Meter Walk Test to be used interchangeably for
      gait speed assessments in healthy, older adults. We therefore recommend using the
      10-Meter Walk Test to obtain the most valid clinical assessment of walking speed
      when using it as a 1-time indicator of health status.

PMID- 22415359
TI  - Gait speed is limited but improves over the course of acute care physical
      therapy.
AB  - BACKGROUND: Gait is a common focus of physical therapists' management of patients
      in acute care settings. Walking speed, the distance a patient covers per unit
      time, has been advocated as a "sixth vital sign." However, the feasibility of
      measuring walking speed and the degree to which walking speed is limited or
      improves over the course of therapy in the acute care setting are unclear.
      PURPOSE: The purpose of this study of patients undergoing physical therapy during
      acute care hospitalization, therefore, was to determine whether walking speed can
      be measured in acute care and whether walking speed is limited and changes over
      the course of therapy. METHODS: This was an observational cross-sectional study.
      Participants were 46 hospital inpatients, mean age 75.0 years (SD = 7.8),
      referred to physical therapy and able to walk at least 20 ft. Information
      regarding diagnosis, comorbidities, physical assistance, device use, body height,
      and weight was obtained. Speed was determined during initial and final physical
      therapy visits while patients walked at their self-selected speed over a marked
      course in a hospital corridor. RESULTS: Therapists reported that walking speed
      was clinically feasible, requiring inexpensive, available resources, 4 minutes'
      additional time, and simple calculations for documentation. Initial walking speed
      was a mean of 0.33 m/s (SD = 0.21; 95% confidence interval [CI]: 0.27-0.39),
      whereas final speed was 0.37 m/s (SD = 0.20; 95% CI: 0.31-0.43). The Wilcoxon
      test showed the increase in walking speed (0.04 m/s) to be significant (P = .005)
      over a mean therapy period of 2.0 days (SD = 1.4) and total hospitalization
      period of 5.5 days (SD = 3.6). The effect size and standardized response mean
      were 0.19 and 0.36, respectively. Minimal detectable change was 0.18 m/s.
      CONCLUSION: Walking speed is a feasible measure for patients admitted to an acute
      care hospital. It shows that patients walk slowly relative to community
      requirements but that their speed improves even over a short course of therapy.

PMID- 22415360
TI  - Synthesis of amphiphilic [PEO(PCL)2] triarm star-shaped block copolymers: a
      promising system for in cell delivery.
AB  - The paper reports on a simple method of synthesizing [PEO(PCL)(2)] triarm star
      shaped copolymers by a combination of Michael-addition type reaction and ring
      opening polymerization. A Michael-addition reaction yielded a PEO end-capped by
      two hydroxyl groups-a [PEO(OH)(2)] macroinitiator-which was used for sequential
      building of PCL blocks. The macroinitiator and copolymers were analyzed by FTIR,
      (1)H NMR spectroscopy and SEC. The self-assembly behavior of the copolymers in
      aqueous media was studied by UV-Vis spectroscopy. The size and morphology of the
      obtained micelles were determined by TEM. None of the polymers had cytotoxic
      effects in vitro. Cellular uptake studies showed the accumulation of neutral red
      loaded micelles in the perinuclear area of human hepatocellular carcinoma cells
      revealing a cellular uptake associated with macropinocytosis and caveolae
      mediated endocytosis. The accumulation had a sustained effect over 3 days
      pointing at the potential application of the copolymers micelles as a drug
      delivery system.

PMID- 22415361
TI  - Evaluation of the controlled release ability from the poly(2-hydroxyethyl
      methacrylate-co-3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5]-undecane) polymer network
      synthesized in the presence of beta-cyclodextrin.
AB  - The study presents the possibility to use the 2-hydroxyethyl methacrylate--HEMA
      copolymer with a comonomer with spiroacetal moiety, 3,9-divinyl-2,4,8,10
      tetraoxaspiro[5.5]-undecane)-U, as polymer network for loading the indomethacin-
      INN as drug model, and also, the controlled release evaluation of the prepared
      bioactive system. The macromolecular compounds were prepared by radical
      dispersion polymerization in the presence of a pair of surfactants. The use of
      cyclodextrin as surfactant allowed the building of the host-guest complexes by
      inclusion of hydrophobic molecules. Also, the cyclodextrin supplemented the
      hydrogen bonds and the hydrophobic interactions responsible for the stability of
      the achieved complexes. The copolymers composition and the INN inclusion onto the
      polymeric matrix were confirmed by FTIR analysis. The porous structure of the
      lyophilized P(HEMA-U) samples was illustrated by SEM images. The swelling studies
      evidenced the interdependence between P(HEMA-U) network properties and the
      spiroacetal moiety amount. Thus, the copolymers presented the increase of the
      equilibrium swelling degree with pH and temperature. Also, the polymeric matrices
      manifested dual sensitivity with pH and temperature. The in vitro release of the
      INN drug from the polymeric network as well as the in vivo experimental studies
      evidenced the benefit consequence of the spiroacetal compound presence. The
      clinical observation of the experimental groups does not show any behavioral
      modifications to suggest a possible toxic effect of these polymeric formulations
      with and without INN.

PMID- 22415362
TI  - Long-term conversion of 45S5 bioactive glass-ceramic microspheres in aqueous
      phosphate solution.
AB  - The conversion of 45S5 glass and glass-ceramics to a hydroxyapatite (HA)-like
      material in vitro has been studied extensively, but only for short reaction times
      (typically <3 months). In this paper, we report for the first time on the long
      term conversion of 45S5 glass-ceramic microspheres (designated 45S5c) in an
      aqueous phosphate solution. Microspheres of 45S5c (75-150 MUm) were immersed for
      10 years at room temperature (~25  degrees C) in K(2)HPO(4) solution with a
      concentration of 0.01 M or 1.0 M, and with a starting pH of 7.0 or 9.5. The
      reacted 45S5c microspheres and solutions were analyzed using structural and
      analytical techniques. Only 25-45 vol% of the 45S5c microspheres were converted
      to an HA-like material after the 10 year reaction. In solutions with a starting
      pH of 9.5, an increase in the K(2)HPO(4) concentration from 0.01 to 1.0 M
      resulted in a doubling of the volume of the microspheres converted to an HA-like
      material but had little effect on the composition of the HA-like product. In
      comparison, reaction of the 45S5c microspheres in the solution with a starting pH
      of 7.0 resulted in an HA-like product in the 0.01 M K(2)HPO(4) solution but a
      calcium pyrophosphate product, Ca(10)K(4)(P(2)O(7))(6).9H(2)O, in the 1.0 M
      solution. The consequences of these results for the long-term use of 45S5 glass
      ceramics in biomedical applications are discussed.

PMID- 22415363
TI  - Siloxane-poly(lactic acid)-vaterite composites with 3D cotton-like structure.
AB  - Trace amounts of ionic calcium and silicon species have been reported to
      stimulate the proliferation, differentiation, and mineralization of bone-forming
      cells. Composite materials comprising siloxane-doped calcium carbonate (vaterite)
      particles and poly(L-lactic acid) have been developed [siloxane-poly(lactic acid)
      vaterite hybrid-composite, SiPVH] so far; they were designed such that calcium
      and silicate ions are gradually released from SiPVH and they show the chronic
      effects of ions on cellular activities. In the present work, SiPVH with a 3D
      cotton-like structure was prepared by electrospinning to obtain the major
      advantages of excellent bioactivity and ease of handling for bone filling
      surgery. The diameter of the fibrous skeletons that form structure of the cotton
      like SiPVH was controlled to ~10 MUm to achieve cellular migration into the
      spaces between fibers. The resulting cotton-like SiPVH showed good flexibility.
      The fiber surface was coated rapidly with numerous particles of several hundred
      nanometers in size by alternate soaking in CaCl(2) and Na(2)HPO(4). The treated
      cotton-like material, which released calcium and silicate ions gradually, showed
      good cellular migration behavior into the 3D structure in cell culture tests
      using murine osteoblast-like MC3T3-E1 cells.

PMID- 22415364
TI  - Development of fibroblast culture in three-dimensional activated carbon fiber
      based scaffold for wound healing.
AB  - This work developed a novel bi-layer wound dressing composed of 3D activated
      carbon fibers that allows facilitates fibroblast cell growth and migration to a
      wound site for tissue reconstruction, and the gentamicin is incorporated into a
      poly(gamma-glutamic acid)/gelatin membrane to prevent bacterial infection. In an
      in vitro, field emission scanning electron microscopy shows that rat skin
      fibroblasts appeared and spread on the surface of activated carbon fibers, and
      penetrated the interior and exterior of the 3D activated carbon fiber construct
      to a depth of roughly 200 MUm. An in vivo analysis shows that fibroblast cells
      containing the proposed 3D scaffold had the potential of a biologically
      functionalized dressing to accelerate wound closure. Additionally, fibroblasts
      migrated to the wound site in a bi-layer wound dressing containing fibroblasts,
      enhancing fibronectin and type I collagen expression, resulting in faster skin
      regeneration than that achieved with a TegadermTM hydrocolloid dressing or gauze.

PMID- 22415366
TI  - Sperm are promiscuous and CatSper is to blame....

PMID- 22415365
TI  - Cohesin-SA1 deficiency drives aneuploidy and tumourigenesis in mice due to
      impaired replication of telomeres.
AB  - Cohesin is a protein complex originally identified for its role in sister
      chromatid cohesion, although increasing evidence portrays it also as a major
      organizer of interphase chromatin. Vertebrate cohesin consists of Smc1, Smc3,
      Rad21/Scc1 and either stromal antigen 1 (SA1) or SA2. To explore the functional
      specificity of these two versions of cohesin and their relevance for embryonic
      development and cancer, we generated a mouse model deficient for SA1. Complete
      ablation of SA1 results in embryonic lethality, while heterozygous animals have
      shorter lifespan and earlier onset of tumourigenesis. SA1-null mouse embryonic
      fibroblasts show decreased proliferation and increased aneuploidy as a result of
      chromosome segregation defects. These defects are not caused by impaired
      centromeric cohesion, which depends on cohesin-SA2. Instead, they arise from
      defective telomere replication, which requires cohesion mediated specifically by
      cohesin-SA1. We propose a novel mechanism for aneuploidy generation that involves
      impaired telomere replication upon loss of cohesin-SA1, with clear implications
      in tumourigenesis.

PMID- 22415367
TI  - Equal opportunity for all.

PMID- 22415369
TI  - Human mitotic chromosome structure: what happened to the 30-nm fibre?

PMID- 22415368
TI  - A unique role of cohesin-SA1 in gene regulation and development.
AB  - Vertebrates have two cohesin complexes that consist of Smc1, Smc3, Rad21/Scc1 and
      either SA1 or SA2, but their functional specificity is unclear. Mouse embryos
      lacking SA1 show developmental delay and die before birth. Comparison of the
      genome-wide distribution of cohesin in wild-type and SA1-null cells reveals that
      SA1 is largely responsible for cohesin accumulation at promoters and at sites
      bound by the insulator protein CTCF. As a consequence, ablation of SA1 alters
      transcription of genes involved in biological processes related to Cornelia de
      Lange syndrome (CdLS), a genetic disorder linked to dysfunction of cohesin. We
      show that the presence of cohesin-SA1 at the promoter of myc and of protocadherin
      genes positively regulates their expression, a task that cannot be assumed by
      cohesin-SA2. Lack of SA1 also alters cohesin-binding pattern along some gene
      clusters and leads to dysregulation of genes within. We hypothesize that impaired
      cohesin-SA1 function in gene expression underlies the molecular aetiology of
      CdLS.

PMID- 22415370
TI  - First principles studies of the graphene-phenol interactions.
AB  - Studies of the interaction between phenol and intrinsic graphene, as well as
      phenol and aluminum doped graphene layer are performed using first principles
      total energy calculations within the periodic density functional theory. A 4x4
      periodic structure is used to explore the adsorption of a phenol molecule on the
      intrinsic graphene and on aluminum doped graphene layer. The electron-ion
      interactions are modeled using ultra-soft pseudo-potentials, and the exchange
      correlation energies are treated according to the generalized gradient
      approximation (GGA) with the PBE parameterization. We consider different molecule
      orientations: parallel and perpendicular to the graphene layer to relax the
      atomic structure. To explain the optimized atomic geometry we determine binding
      energies for all cases and the density of states (DOS) and partial DOS for the
      most relevant configurations. Results indicate that the direct interaction of
      oxygen with aluminum yields the ground state geometry with the phenol molecule
      adsorbed on the graphene layer. Binding energies and DOS structures also
      demonstrate that the ground state configuration is that where the O and Al atoms
      interact with a separation distance of 1.97 A.

PMID- 22415372
TI  - The contribution of school breaks to the all-day physical activity of 9- and 10
      year-old overweight and non-overweight children.
AB  - OBJECTIVES: This study examines whether moderate-to-vigorous physical activity
      (MVPA), in at least 30-min school breaks (SB), helps to achieve the health
      related amount of daily physical activity (PA) and whether these exercises
      influence after-school PA. METHODS: The ActiTrainer-based PA was monitored over
      two school days in 239 children aged from 9 to 10 (57.3% female; 20.1%
      overweight, and 19.2% obese), in Katowice, in February 2010. PA was assessed
      based on steps, heart rate, and duration of PA. RESULTS: MVPA, for 30 min during
      SB, represented an average of 1,258 steps for overweight girls and 1,620 steps
      for boys, and 1,336 steps for non-overweight girls and 1,758 steps for boys.
      Children with 30 min of MVPA during SB attained a higher daily amount of steps (p
      < 0.001) and duration of overall PA (p < 0.01), in comparison with less
      physically active children. CONCLUSION: The daily 30 min of MVPA during SB
      amounts to 12.5% of the overall number of steps for girls and 16.3% for boys,
      thus contributing to higher school PA and overall PA and leading to the
      achievement of the health-related minimum of PA.

PMID- 22415373
TI  - Do social relations explain health inequalities? Evidence from a longitudinal
      survey in a changing eastern German region.
AB  - OBJECTIVES: This study explores the contribution of social relations to explain
      inequalities in self-rated health in a changing north-eastern German region. So
      far, there are only few studies that analysed the mediating effects of social
      relations in a longitudinal design. METHODS: We used data from the Study of
      Health in Pomerania (SHIP) consisting of 3,300 randomly selected men and women at
      baseline (2001), and at the 5-year follow-up (2006). Indicators of social
      inequality were education, equivalent household income and occupational status.
      Social relations were estimated by the Social Integration Index (SII) and the
      perceived instrumental and emotional support. Self-rated general health was
      assessed at both waves of data collection. RESULTS: Depending on the indicators
      used, social relations explain up to 35% of the inequalities in self-rated
      health. Changes in odds ratios are slightly more pronounced when education and
      income are used as inequality indicator and when adjusting for the SII.
      CONCLUSIONS: Overall findings suggest that social relations are an important
      explanatory factor for health inequalities in a deprived German region.

PMID- 22415374
TI  - Acid extraction to a hydrophobic ionic liquid: the role of added
      tributylphosphate investigated by experiments and simulations.
AB  - We have studied the extraction of four HA acids (HNO(3), HReO(4), HClO(4), HCl)
      to a hydrophobic ionic liquid (IL) 1-butyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)amide (BMI(+) Tf(2)N(-)) at room temperature, in a
      wide range of acidic concentrations in water. The effect of tributylphosphate
      (TBP) as co-solvent is investigated. According to experimental observations,
      water dragging to the IL phase increases with added TBP and/or acids. Acid
      extraction is found to be weak, however, for the four acids except for
      concentrated HNO(3) (>3 M). Molecular dynamics simulations on model biphasic
      systems show that TBP is not surface active, but well dissolved in the IL. They
      also reveal the importance of HA acid model (either totally or half dissociated)
      and of the TBP content on acid extraction to the IL. Furthermore, they show that
      "the proton" can be extracted by TBP (H(3)O(+)(TBP)(3)"complex") without its A(-)
      conjugated base, via a cation transfer mechanism (BMI(+) transfer to water).
      Experiments and simulations show that TBP plays an important role in the mutual
      solubility between water and ionic liquid, by different amounts, depending on the
      HA acid. On the other hand, both approaches indicate that a HTf(2)N containing
      aqueous solution completely mixes with the [BMI][Tf(2)N] IL that contains the
      same Tf(2)N(-) anion.

PMID- 22415376
TI  - Qualitative and quantitative intravaginal targeting: key to anti-HIV-1
      microbicide delivery from test tube to in vivo success.
AB  - The past decade has seen several effective anti-HIV-1 agent discoveries, yet
      microbicides continue to disappoint clinically. Our review expounds the view that
      unsatisfactory microbicide failures may be a result of inefficient delivery
      systems employed. We hereby propose a thorough scientific qualitative and
      quantitative investigation of important aspects involved in HIV-1 transmission as
      a prerequisite for microbicide delivery. Intravaginal targeting of HIV-1
      increases the chances of microbicide success, wherein vaginal microenvironmental
      factors including pH should be maintained at HIV-1 prohibitive acidic levels
      simultaneously to ward off other sexually transmitted diseases, which compromise
      vaginal epithelial barrier properties. Furthermore, choice of receptors to target
      both on HIV-1 and on target cells is vital in deterring transmission. Appropriate
      modeling of virus-target cell interactions as well as targeting early stages of
      the HIV-1 infection accompanied by computation and delivery of appropriate
      microbicide quantities could revolutionize microbicide research, ultimately
      delivering a female-controlled HIV-1 prevention modality appropriately.

PMID- 22415375
TI  - Signaling networks regulating tooth organogenesis and regeneration, and the
      specification of dental mesenchymal and epithelial cell lineages.
AB  - Teeth develop as ectodermal appendages from epithelial and mesenchymal tissues.
      Tooth organogenesis is regulated by an intricate network of cell-cell signaling
      during all steps of development. The dental hard tissues, dentin, enamel, and
      cementum, are formed by unique cell types whose differentiation is intimately
      linked with morphogenesis. During evolution the capacity for tooth replacement
      has been reduced in mammals, whereas teeth have acquired more complex shapes.
      Mammalian teeth contain stem cells but they may not provide a source for
      bioengineering of human teeth. Therefore it is likely that nondental cells will
      have to be reprogrammed for the purpose of clinical tooth regeneration. Obviously
      this will require understanding of the mechanisms of normal development. The
      signaling networks mediating the epithelial-mesenchymal interactions during
      morphogenesis are well characterized but the molecular signatures of the
      odontogenic tissues remain to be uncovered.

PMID- 22415378
TI  - Management strategies to optimize clinical outcomes after acute traumatic spinal
      cord injury: integration of medical and surgical approaches.
AB  - Although spinal cord injury (SCI) is approximately one-tenth as common as
      traumatic brain injury, its effects, at both a personal and societal level, are
      particularly devastating. At present, there is no single therapy that has
      demonstrated a uniform ability to improve neurological outcomes for SCI patients
      at long-term follow-up. In spite of this, the last 30 years have borne witness to
      numerous incremental advances within the field of spinal trauma including the
      incorporation of standardized neurological assessment tools, the completion of
      several large therapeutic efficacy trials and the development of modern day
      surgical classification systems. In this article we review the current evidence
      surrounding the medical and surgical management of SCI, as well as identify areas
      where future research is needed.

PMID- 22415379
TI  - Motion preservation in cervical spine: review.
AB  - Cervical disc replacement is an innovative technology that preserves motion at
      the instrumented level and has evolved as a potential alternative to spinal
      fusion for the treatment of cervical radiculopathy and myelopathy. Despite the
      excellent results of anterior cervical discectomy and fusion, arthroplasty allows
      for motion preservation which may be beneficial. Although the initial and midterm
      results from the randomized clinical trials demonstrated safety and equivalent
      clinical success as compared to anterior cervical fusion; the evidence
      establishing the superiority of arthroplasty over fusion in terms of preventing
      adjacent segment degeneration/disease is not available at this time.

PMID- 22415377
TI  - Effect of race and socioeconomic status on surgical margins and biochemical
      outcomes in an equal-access health care setting: results from the Shared Equal
      Access Regional Cancer Hospital (SEARCH) database.
AB  - BACKGROUND: The impact of race and socioeconomic status (SES) in prostate cancer
      (CaP) outcomes has been well-studied, but controversy remains. The associations
      of race/SES with intermediate CaP outcomes, including positive surgical margin
      (PSM) and biochemical recurrence (BCR), were explored in an equal-access setting.
      METHODS: Data were retrospectively collected from 2502 men in the Shared Equal
      Access Regional Cancer Hospitals (SEARCH) database who underwent radical
      prostatectomy from 1989 to 2010. SES (income, education, employment, and poverty)
      was estimated from linkage of home ZIP code to census data. Logistic regression
      with adjustment for pre- and postoperative covariates estimated risk for
      associations between race/SES and pathologic outcomes. Cox proportional hazards
      models estimated risk for associations between race/SES and time to BCR. RESULTS:
      Black men were more likely to have lower SES than white men (P < .001). On
      multivariate analysis, race was not associated with PSM, but higher SES was
      associated with less PSM and fewer Gleason sum >= 7 pathologic tumors when SES
      was assessed by education, employment, or poverty (P trend <= .051) and income,
      employment, or poverty (P trend <= 0.059), respectively. Crude Cox models showed
      black men had higher BCR risk (hazards ratio = 1.20, 95% confidence interval =
      1.05-1.38, P = .009) that persisted after adjustment for covariates including SES
      (hazards ratio >= 1.18, P <= .040). Higher SES measured by income and poverty
      were associated with less BCR, but only for black men (P trend <= .048).
      CONCLUSIONS: Even in an equal-access setting, higher SES predicted lower PSM
      risk, and race persisted in predicting BCR despite adjustment for SES. Low SES
      black patients may be at greatest risk for postprostatectomy BCR.

PMID- 22415380
TI  - Minimally invasive surgery for the lumbar spine.
AB  - Minimally invasive spine surgery is a rapidly developing field that has the
      potential to decrease surgical morbidity and improve recovery compared to
      traditional spinal approaches. Minimally invasive approaches have been developed
      for all regions of the spine, but have been best documented for degenerative
      conditions of the lumbar spine. Lumbar decompression and lumbar interbody fusion
      are two of the most well-studied minimally invasive surgical approaches. This
      article will review both the rationale and technique for minimally invasive
      lumbar decompression and for a minimally invasive transforaminal lumbar interbody
      fusion (TLIF).

PMID- 22415381
TI  - A review of image-guided spinal surgery.
AB  - Image-guided spinal surgery has evolved rapidly in recent years. This review
      highlights the advances in image-guided spinal surgery during this evolution. The
      current literature regarding image-guided spinal surgery will be discussed. In
      addition, several aspects of image-guided spinal surgery will be focused on,
      including its learning curve and influence on operating room time, as well as its
      effect on surgeon radiation exposure. The accuracy of instrumentation placement
      with this technology and current applications will also be addressed.

PMID- 22415382
TI  - Primitive neuroectodermal tumors of the central nervous system associated with
      genetic and metabolic defects.
AB  - AIM: To evaluate the genetic, congenital and metabolic disorders which were
      detected concurrently with primitive neuroectodermal tumors (PNET) of the central
      nervous system in children. METHODS: Medical records of 1030 children who were
      admitted to our department with diagnosis of brain tumor between 1975 and 2005
      were reviewed retrospectively. Medulloblastoma and supratentorial PNETs were
      detected in 289 patients. They were reviewed for associated metabolic conditions,
      genetic and congenital defects. RESULTS: One of the following conditions were
      detected in 10 patients with medulloblastoma and supratentorial PNETs:
      Neurofibromatosis type 1, Gorlin syndrome, juvenile polyposis coli, cancer prone
      syndrome of total premature chromatid separation and Fanconi anemia, bilateral
      retinoblastoma, L-2-hydroxyglutaric aciduria, Gilbert syndrome, gray platelet
      syndrome, cleft lip-palate and left renal agenesis. In the patients with multiple
      malignant diseases, cancer prone syndrome of total premature chromatid separation
      and Fanconi anemia, Gorlin syndrome and juvenile polyposis coli were diagnosed
      after diagnosis of the malignant tumors. Medulloblastoma was the first
      manifestation in the case with Gorlin syndrome. In case with retinoblastoma,
      pineal PNET was detected 2 months after diagnosis of retinoblastoma. Cleft lip
      palate and L-2-Hydroxyglutaric aciduria were detected previously in the patients
      before their brain tumors whereas Gray platelet, Gilbert syndrome and left renal
      agenesis were diagnosed during treatment of medulloblastoma. CONCLUSION:
      Associated genetic, metabolic and congenital conditions were detected in 3.5% of
      the cases. Thus the patients with PNET should be followed for these defects.

PMID- 22415383
TI  - Resection of a large spinal intradural ependymoma using a limited unilateral
      laminectomy approach in the lumbosacral region.
AB  - Ependymomas are the most common gliomas of the lower spinal cord, conus
      medullaris and filum terminale. Although there are several surgical modalities
      indicated in the removal of spinal tumors, total laminectomy is the conventional
      method used. However, surgical complications, such as spinal deformities and
      instability are more common with this approach compared to limited unilateral
      hemilaminectomy. To present the clinical and radiologic results of patient with a
      large spinal intradural ependymoma via a limited posterior unilateral laminectomy
      approach in the lumbosacral region. The aim of this study was to present a
      modified duramater incisions and surgical positions setup, and discussed the
      major controversies in treatment in the literature. This article reports the
      surgical resection of a lumbosacrally localized ependymoma in a 25-year-old male
      patient using unilateral laminectomy at the L4 to S3 levels. The tumor was
      removed with any difficulty in reaching to contralateral side. A follow-up lumbar
      magnetic resonance imaging scan with and without contrast performed 18 months
      postoperatively showed no residual or recurrent tumor lesions. This procedure may
      be more difficult than the conventional total laminectomy as suturing of the
      duramater. However, modified duramater incisions and setup of microscope
      operating table provides best facilitates to surgery manipulation. Besides,
      unilateral limited laminectomy protected the posterior supporting elements. In
      order to reduce the postoperative complications and minimize the destruction of
      tissue, unilateral limited hemilaminectomy is recommended for the removal of
      intradural tumors. This technique facilitates the return of the patient to
      ordinary life.

PMID- 22415384
TI  - Congenital dermal sinus of the cervical spine: clinical characteristics and
      management.
AB  - Congenital dermal sinus (CDS) in the cervical region is extremely rare with only
      few cases reported in the literature. This study reports a young case of CDS, by
      which we demonstrate the clinical characteristics and management of cervical CDS,
      particularly in kids. A 2-year and 7-month-old male child who presented with a
      one-year history of difficulty in holding objects by hands was diagnosed to have
      harbored a CDS in the cervical spine since birth. Neurological examination
      demonstrated mild weakness in both hands and also atrophy in intrinsic hand
      muscles. Surgery was performed right after diagnosis. Intraoperatively, the sinus
      tract was totally excised, and untethering was performed. No complications were
      found after operation. Histopathological examination suggested dorsal dermal
      sinus. During the follow-up of three years, the patient presented a stable
      neurologic deficit but did not suffer from an aggravation or improvement of
      nervous symptoms. At three-year follow-up, the patient was a stable neurologic
      deficit, and MRI revealed no evidence of the untethered cervical spinal cord and
      dermal sinus tract. The management strategies of CDS are early surgical treatment
      to prevent the development of neurological defects.

PMID- 22415385
TI  - Operative case of Langerhans'cell histiocytosis of the skull with dural invasion.
      An immunohystochemical study of ki-67 expression of eosinophilic granuloma: case
      report and review of the literature.
AB  - Eosinophilic granuloma (EG), Letterer-Siwe disease and Hand-Schuller-Christian
      disease are collectively called Langherans-cell histiocytosis (LCH). While the
      latter two are systemic diseases, the former is a localized form of
      histiocytosis. Solitary EG of the skull are rare lesions characterized by a
      natural history not well defined yet. In this context, we report a case of a 23
      year-old male suffering for a recurrent and progressive right parietal headache.
      On computed tomography (CT) it was observed an ostelytic lesion which on magnetic
      resonance imaging (MRI) appeared as an hyperintense soft mass on both T1 and T2
      weighted images. The lesion showed a marked and heterogeneous enhancement after
      gadolinium administration. The surgical excision was complete and the severe
      headache disappeared. Immunohistochemical analysis of the specimen indicated an
      eosinophilic granuloma characterized by Ki-67 nuclear antigen expression with a
      labeling index of 20%. In the pertinent literature we have found two aggressive
      cases of EG showing the Ki-67 expression with a respectively 6.2% (occipital bone
      granuloma) and 10% (parietal bone granuloma) labeling index. That high
      proliferative activity suggests a local Langherans' cell proliferation along with
      an exuberant inflammatory response and also explains the aggressive clinical
      course and the rapid expansion of the lesion observed in some rare cases of
      solitary EG. This is the third case-report of calvarial EG characterized by Ki-67
      nuclear antigen expression.

PMID- 22415386
TI  - Surgical approaches to meningiomas of the trigone.

PMID- 22415387
TI  - Noninvasive continuous arterial blood pressure monitoring with Nexfin(r).
AB  - BACKGROUND: If invasive measurement of arterial blood pressure is not warranted,
      finger cuff technology can provide continuous and noninvasive monitoring. Finger
      and radial artery pressures differ; Nexfin(r) (BMEYE, Amsterdam, The Netherlands)
      measures finger arterial pressure and uses physiologic reconstruction
      methodologies to obtain values comparable to invasive pressures. METHODS: Intra
      arterial pressure (IAP) and noninvasive Nexfin arterial pressure (NAP) were
      measured in cardiothoracic surgery patients, because invasive pressures are
      available. NAP-IAP differences were analyzed during 30 min. Tracking was
      quantified by within-subject precision (SD of individual NAP-IAP differences) and
      correlation coefficients. The ranges of pressure change were quantified by within
      subject variability (SD of individual averages of NAP and IAP). Accuracy and
      precision were expressed as group average +/- SD of the differences and
      considered acceptable when smaller than 5 +/- 8 mmHg, the Association for the
      Advancement of Medical Instrumentation criteria. RESULTS: NAP and IAP were
      obtained in 50 (34-83 yr, 40 men) patients. For systolic, diastolic, mean
      arterial, and pulse pressure, median (25-75 percentiles) correlation coefficients
      were 0.96 (0.91-0.98), 0.93 (0.87-0.96), 0.96 (0.90-0.97), and 0.94 (0.85-0.98),
      respectively. Within-subject precisions were 4 +/- 2, 3 +/- 1, 3 +/- 2, and 3 +/-
      2 mmHg, and within-subject variations 13 +/- 6, 6 +/- 3, 9 +/- 4, and 7 +/- 4
      mmHg, indicating precision over a wide range of pressures. Group average +/- SD
      of the NAP-IAP differences were -1 +/- 7, 3 +/- 6, 2 +/- 6, and -3 +/- 4 mmHg,
      meeting criteria. Differences were not related to mean arterial pressure or heart
      rate. CONCLUSION: Arterial blood pressure can be measured noninvasively and
      continuously using physiologic pressure reconstruction. Changes in pressure can
      be followed and values are comparable to invasive monitoring.

PMID- 22415388
TI  - Acute kidney injury and extrarenal organ dysfunction: new concepts and
      experimental evidence.
AB  - Acute kidney injury (AKI) is a frequent complication in the intensive care unit
      with limited therapeutic modalities. Although survival from isolated AKI has
      improved with recent advancements in renal replacement therapy, mortality from
      AKI complicated by multiorgan dysfunction has remained unchanged and is estimated
      to be approximately 50%. Hence, defining and better understanding the
      pathophysiology of distant organ dysfunction associated with AKI is clinically
      important because it may lead to new treatment strategies. In animal models, it
      has become increasingly clear that AKI is not an isolated event but results in
      remote organ dysfunction involving the heart, lungs, liver, intestines, and brain
      through an inflammatory mechanism that involves neutrophil migration, cytokine
      expression, and increased oxidative stress. The purpose of this brief review is
      to summarize the human and basic science evidence for AKI and its detrimental
      effects on distant organs.

PMID- 22415390
TI  - The need for large clinical studies in perioperative medicine.

PMID- 22415391
TI  - Targeted prophylaxis of postoperative delirium.

PMID- 22415392
TI  - Comparing oxygen targeting in preterm infants between the Masimo and Philips
      pulse oximeters.

PMID- 22415393
TI  - Infant, obstetrical and maternal characteristics associated with thromboembolism
      in infancy: a nationwide population-based case-control study.
AB  - OBJECTIVES: To identify infant, obstetrical and maternal characteristics
      associated with arterial ischaemic stroke (AIS) and venous thromboembolism (VTE)
      in infancy (<1 year). DESIGN: Nationwide, population-based nested case-control
      study. All infants with a verified first-time diagnosis of AIS, VTE or both in
      Denmark through the years 1994-2006 were included, and 10 population controls
      were selected for each case. RESULTS: Case-infants presented with AIS (n=71) or
      VTE (n=38). AIS in infancy was associated with primiparity (adjusted OR 5.9 CI
      95% 3.0 to 11.6)), delivery by an emergency caesarean section (adjusted OR 1.9
      (CI 95% 1.0 to 3.3)), and post-term birth (adjusted OR 2.2 (CI 95% 1.1 to 4.8)).
      Male sex was associated with an increased risk of AIS among neonates (crude OR
      1.8 (CI 95% 1.0 to 3.4)) but not among later born (crude OR 0.6 (CI 95% 0.2 to
      1.4)). Risk factors for VTE in infancy included preterm birth (adjusted OR 5.5
      (CI 95% 1.8 to 16.9)), low Apgar score (adjusted OR 9.2 (CI 95% 1.9 to 45.2)),
      and multiple births (adjusted OR 7.1 (CI 95% 1.1 to 48.1)). Previous maternal
      thromboembolism and pregnancy-related disorders were not associated with the risk
      of thromboembolism in the children. CONCLUSION: Several apparently independent
      infant, obstetrical and maternal characteristics were associated with
      thromboembolism in early life.

PMID- 22415394
TI  - Isolated left ventricular noncompaction: what do we really know?
AB  - Isolated left ventricular noncompaction (ILVNC) is a myocardial disorder thought
      to occur as a result of an arrest in embryogenesis. Recently, it has been
      classified as a genetic cardiomyopathy. Familial and sporadic forms of ILVNC have
      been documented. There is considerable genetic heterogeneity among familial
      forms, although sarcomeric mutations are the most common genetic mutations.
      Issues related to familial screening require careful consideration and future
      research. There is considerable controversy regarding several aspects relating to
      pathogenesis, diagnosis, and management of subjects with ILVNC. Differentiating
      some cases of ILVNC from normal variant myocardial architecture is challenging
      and requires future work. This review is intended to provide clinicians insight
      into several aspects of these challenging issues and offer some practical
      guidance in dealing with some of these difficult clinical scenarios.

PMID- 22415395
TI  - Early detection of chemotherapy-related left ventricular dysfunction.
AB  - Modern advances in cancer treatment have resulted in improved survival. As a
      result, effects of cancer therapy on other organ systems such as the heart are
      more likely to become clinically relevant. One such possibility is chemotherapy
      related left ventricular dysfunction. Although in clinical practice
      cardiotoxicity is evaluated by symptoms and left ventricular ejection fraction,
      these occur relatively late in the disease process after the heart's compensatory
      mechanisms have been expended. Ideally, left ventricular dysfunction would be
      identified early so that cancer patients and their physicians can make informed
      decisions about their therapeutic options and institute careful surveillance and
      early initiation of cardioprotective medication where appropriate. This review
      discusses the role of echocardiography to detect subclinical left ventricular
      dysfunction in cancer patients exposed to chemotherapy with potential
      cardiotoxicity, particularly anthracyclines and trastuzumab.

PMID- 22415396
TI  - Isolated ultrafiltration in heart failure patients.
AB  - Most heart failure hospitalizations are due to volume overload, which contributes
      to disease progression. Heart failure decompensation is typically treated with
      intravenous diuretics, which are of limited efficacy especially in patients with
      underlying chronic kidney disease. Since the introduction of hemodialysis,
      ultrafiltration has been used to remove excess body fluid. Newer, simplified
      isolated ultrafiltration devices make ultrafiltration feasible at most hospitals
      and in less acute care settings. Veno-venous ultrafiltration is characterized by
      transport of solutes and water across a semipermeable membrane in response to a
      transmembrane pressure gradient generated by a peristaltic pump. Monitoring of
      ultrafiltration requires a combination of clinical and biomarkers values.
      Hemodynamic instability due to overaggressive fluid removal must be avoided.
      Based on recent clinical trials, practice guidelines state that ultrafiltration
      is reasonable for patients with congestion refractory to medical therapy (Class
      IIa, Level of Evidence B). Unanswered questions regarding ultrafiltration in
      heart failure patients include optimal fluid removal rates, effect on long-term
      survival, and cost.

PMID- 22415397
TI  - The comorbidity conundrum: a focus on the role of noncardiovascular chronic
      conditions in the heart failure patient.
AB  - The rapid aging of the US population combined with improvements in modern
      medicine has created a new public health concern of comorbidity, a chronic
      condition that co-exists with a primary illness. Over 141 million Americans
      suffer from one or more comorbid conditions. In the heart failure (HF) patient,
      this comorbidity burden is particularly high, with over 40% of patients having
      five or more chronic conditions. These comorbidities can vary from being a risk
      factor to a cause of HF progression or even a precipitating factor for
      decompensation. Comorbidities, particularly the noncardiovascular conditions,
      have been associated with greater health resource utilization, poor health
      outcomes, and increased mortality. To minimize the negative impact that these
      comorbidities have on patient outcomes, appropriate attention should be paid to
      identifying, prioritizing, and managing each condition; minimizing medication
      complexity and polypharmacy; and improving overall coordination of care between
      providers and patients.

PMID- 22415398
TI  - Comparison of FIGO 1988 and 2009 staging systems for endometrial carcinoma.
AB  - The objective of this study was to compare FIGO 1988 and 2009 endometrial
      carcinoma staging systems in terms of patient distribution and efficacy in
      predicting prognosis in patients treated with surgery and adjuvant radiotherapy
      (RT). Medical records of 351 patients treated between 1994 and 2009 were
      retrospectively analyzed. Adjuvant RT was in the form of vaginal cuff
      brachytherapy (BRT) in patients with uterine confined disease and risk factors,
      whereas high-risk patients received risk-adapted external pelvic RT. The median
      follow-up time was 55 months (range, 2.5-133 months). Five-year overall (OS) and
      disease-free survival (DFS) for the entire group was 83 and 88%, respectively.
      Stage migration was observed in 188 (54%) patients. Stage migration generally did
      not cause any significant effect in OS and DFS rates. However, 5-year OS and DFS
      for stage I patients with positive peritoneal cytology was significantly lower
      than the other patients with negative cytology in FIGO 2009 system. The survival
      curves overlapped for stage IA, IB and II in the new staging system. On the other
      hand, the division of stage IIIC as IIIC1 and IIIC2 significantly affected the
      prognosis. Patients with stage IIIC2 tumor had 40% OS and 48% DFS rates compared
      to 69 and 66% in stage IIIC1 patients (p=0.002). The major improvement of FIGO
      2009 seems to be the subclassification of stage IIIC disease into IIIC1 and
      IIIC2. The positivity of peritoneal cytology per se seems to have an influence in
      prognosis in our cohort. To withdraw the positive cytology from staging may
      mislead the prognosis estimation in these patients and lead to undertreatment.

PMID- 22415399
TI  - Role of HER2-neu as a prognostic factor for survival and relapse in pT1a-bN0M0
      breast cancer: a systematic review of the literature with a pooled-analysis.
AB  - High levels of human epidermal growth receptor 2 (HER2) expression are associated
      with recurrence and death in breast cancer (BC) patients. We have performed a
      systematic review and meta-analysis in order to evaluate the prognosis for HER2+
      pT1a-bN0M0 BC patients. A search of PubMed and Embase was performed. Studies were
      included if they reported hazard ratios (HRs) with a 95% confidence interval (CI)
      for multivariate analyses of relapse or survival in pT1a-bN0M0, HER2+ BC patients
      treated with surgery and chemotherapy and/or endocrine therapy, but not with
      trastuzumab. A total of 764 patients from seven studies were included in the meta
      analysis. In the pooled analysis, HER2 had a detrimental effect on relapse-free
      (HR 4.68, 95% CI 3.05-7.18; p<0.00001) and distant relapse-free survival, with a
      HR of 5.6 (95% CI 2.65-11.85; p<0.00001). HER2+ status was also linked to
      increased risk of death (HR 3.4, 95% CI 0.86-13.41; p=0.08) and worst BC-specific
      survival (HR 2.61, 95% CI 1.51-4.51; p=0.0006), but these data were presented in
      few studies. HER2+ pT1a-bN0M0 BC is associated with a dismal prognosis. In these
      patients, HER2 has to be taken into account when deciding on adjuvant therapy,
      and trastuzumab should be considered.

PMID- 22415401
TI  - HPLC/APCI mass spectrometry of saturated and unsaturated hydrocarbons by using
      hydrocarbon solvents as the APCI reagent and HPLC mobile phase.
AB  - Saturated and unsaturated, linear, branched, and cyclic hydrocarbons, as well as
      polyaromatic and heteroaromatic hydrocarbons, were successfully ionized by
      atmospheric pressure chemical ionization (APCI) using small hydrocarbons as
      reagents in a linear quadrupole ion trap (LQIT) mass spectrometer. Pentane was
      proved to be the best reagent among the hydrocarbon reagents studied. This
      ionization method generated different types of abundant ions (i.e., [M + H](+),
      M(+*), [M - H](+) and [M - 2H](+ *)), with little or no fragmentation. The
      radical cations can be differentiated from the even-electron ions by using
      dimethyl disulfide, thus facilitating molecular weight (MW) determination. While
      some steroids and lignin monomer model compounds, such as androsterone and 4
      hydroxy-3-methoxybenzaldehyde, also formed abundant M(+*) and [M + H](+) ions,
      this was not true for all of them. Analysis of two known mixtures as well as a
      base oil sample demonstrated that each component of the known mixtures could be
      observed and that a correct MW distribution was obtained for the base oil. The
      feasibility of using this ionization method on the chromatographic time scale was
      demonstrated by using high-performance liquid chromatography (HPLC) with hexane
      as the mobile phase (and APCI reagent) to separate an artificial mixture prior to
      mass spectrometric analysis.

PMID- 22415400
TI  - A study on mutational dynamics of simple sequence repeats in relation to mismatch
      repair system in prokaryotic genomes.
AB  - Mutational bias toward expansion or contraction of simple sequence repeats (SSRs)
      is referred to as directionality of SSR evolution. In this communication, we
      report the mutational bias exhibited by mononucleotide SSRs occurring in the non
      coding regions of several prokaryotic genomes. Our investigations revealed that
      the strains or species lacking mismatch repair (MMR) system generally show higher
      number of polymorphic SSRs than those species/strains having MMR system. An
      exception to this observation was seen in the mycobacterial genomes that are MMR
      deficient where only a few SSR tracts were seen with mutations. This low
      incidence of SSR mutations even in the MMR-deficient background could be
      attributed to the high fidelity of the DNA polymerases as a consequence of high
      generation time of the mycobacteria. MMR system-deficient species generally did
      not show any bias toward mononucleotide SSR expansions or contractions indicating
      a neutral evolution of SSRs in these species. The MMR-proficient species in which
      the observed mutations correspond to secondary mutations showed bias toward
      contraction of polymononucleotide tracts, perhaps, indicating low efficiency of
      MMR system to repair SSR-induced slippage errors on template strands. This bias
      toward deletion in the mononucleotide SSR tracts might be a probable reason
      behind scarcity for long poly A|T and G|C tracts in prokaryotic systems which are
      mostly MMR proficient. In conclusion, our study clearly demonstrates mutational
      dynamics of SSRs in relation to the presence/absence of MMR system in the
      prokaryotic system.

PMID- 22415402
TI  - Epidemic characterization and modeling within herd transmission dynamics of an
      "emerging trans-boundary" camel disease epidemic in Ethiopia.
AB  - A highly acute and contagious camel disease, an epidemic wave of unknown
      etiology, referred to here as camel sudden death syndrome, has plagued camel
      population in countries in the Horn of Africa. To better understand its epidemic
      patterns and transmission dynamics, we used epidemiologic parameters and
      differential equation deterministic modeling (SEIR/D-model) to predict the
      outcome likelihood following an exposure of susceptible camel population. Our
      results showed 45.7, 17.6, and 38.6 % overall morbidity, mortality, and case
      fatality rates of the epidemic, respectively. Pregnant camels had the highest
      mortality and case fatality rates, followed by breeding males, and lactating
      females, implying serious socioeconomic consequences. Disease dynamics appeared
      to be linked to livestock trade route and animal movements. The epidemic
      exhibited a strong basic reproductive number (R (0)) with an average of 16 camels
      infected by one infectious case during the entire infectious period. The epidemic
      curve suggested that the critical moment of the disease development is
      approximately between 30 and 40 days, where both infected/exposed and infectious
      camels are at their highest numbers. The lag between infected/infectious curves
      indicates a time-shift of approximately 3-5 days from when a camel is infected
      and until it becomes infectious. According to this predictive model, of all
      animals exposed to the infection, 66.8 % (n = 868) and 33.2 % (n = 431) had
      recovered and died, respectively, at the end of epidemic period. Hence, if early
      measures are not taken, such an epidemic could cause a much more devastative
      effect, within short period of time than the anticipated proportion.

PMID- 22415403
TI  - Biochemical changes in heat exposed buffalo heifers supplemented with yeast.
AB  - Serum electrolytes, minerals, blood biochemical and plasma enzymes were studied
      in heat exposed buffalo heifers supplemented with yeast powder in feed to
      alleviate the adverse effects of heat stress. Eighteen healthy Murrah buffalo
      heifers (270-280) kg were divided into three groups. Animals of group I were kept
      in shed and served as control, while group II and group III were exposed in a
      psychrometric chamber at 40 degrees C for 4 hrs daily for 16 days continuously.
      The animals in group III were also supplemented with yeast powder at 10 g per
      animal per day. The serum sodium, potassium and chloride levels decreased
      significantly (P < 0.05) in group II and their levels tended to be maintained in
      group III. Serum calcium, magnesium, phosphorus, glucose and total cholesterol
      concentration decreased (P < 0.05) significantly whereas total protein increased
      in group II due to heat stress. The levels of these minerals tended to be normal
      in group III. The plasma concentration of SGOT and SGPT increased significantly
      (P < 0.05), whereas the concentration of plasma alkaline phosphatase and acid
      phosphatase decreased due to thermal exposure. The levels of these enzymes tended
      to be normal in group III. The results indicated significant deviations in blood
      biochemical due to thermal stress and their levels tended to be normal in yeast
      supplemented group of buffalo heifers.

PMID- 22415404
TI  - Titanium elastic nailing radius and ulna fractures in adolescents.
AB  - Over the last 40 years, anatomic reduction with plate stabilization has become
      the standard in adult patients with diaphyseal fractures of the radius and ulna.
      When operative fixation has been indicated in skeletally immature patients with
      these fractures, a variety of techniques have been reported, with intramedullary
      fixation becoming increasingly accepted. There is currently significant
      variability in the treatment of adolescents with forearm fractures. The purpose
      of this study was to investigate the clinical and radiographic outcomes in the
      adolescent population after intramedullary fixation of both bone forearm
      fractures. A retrospective review identified 32 patients 12-18 years of age who
      had undergone intramedullary fixation of both forearm bones in the past 20 years
      at our institution. Galeazzi, Monteggia, radial head, and distal metaphyseal
      fractures were excluded. Radiographic evaluation was performed to determine union
      and postoperative radial bow. Clinical follow-up was carried out for
      postoperative complications and range of motion of the wrist, forearm, and elbow.
      The mean age of the patients was 14.1 years. A total of 19 fractures were closed
      injuries, nine were grade 1, three were grade 2, and one fracture was a grade 3b.
      Of the patients, 15.6% had limited postoperative range of motion. All patients in
      the older age group, 15-18 years of age, had a normal range of motion. A decrease
      in radial bow was not associated with limitation in motion. There was a 98% union
      rate, and all unions occurred by 7.5 months. Only three major complications
      occurred, two refractures and one ulnar hardware migration, and subsequent radius
      nonunion occurred in the one grade 3b injury. Flexible intramedullary nailing of
      both bone forearm fractures provides reliable bony union and excellent
      postoperative clinical results in adolescents. Level of evidence, IV.

PMID- 22415405
TI  - 90Y-labeled tin fluoride colloid as a promising therapeutic agent: preparation,
      characterization, and biological study in rats.
AB  - In this study, tin fluoride colloid (SnF-c) was prepared, labeled with yttrium-90
      ((90)Y), and characterized with respect to its physicochemical properties and
      biological behavior in an animal model. Particle size of SnF-c, at constant
      concentration of SnF(2), was dependent on pH, concentration of sodium fluoride
      (NaF), temperature, and time. The particle size of SnF-c decreased with an
      increase in NaF concentration and a decrease in reaction mixture pH.
      Radiolabeling yield of (90)Y-SnF-c at higher temperature increased and it was
      greater than 98% for the preparation at 95  degrees C. The (90)Y-SnF-c
      demonstrated high in vitro stability both in human serum and human synovial fluid
      at 37  degrees C up to 7 days. In vivo distribution studies in healthy male
      Wistar rats of (90)Y-SnF-c (particles <1 MUm), following intravenous
      administration, revealed that the localization takes place preferably in the
      liver. The (90)Y-SnF-c (particles >1 MUm) was well retained in the synovial space
      for 96 h after intra-articular injection, whereas leakage of (90)Y from the joint
      was 1.96% over this period. Because of high labeling yield and stability, (90)Y
      SnF-c might be a promising agent for radiosynovectomy or therapy of liver
      malignancies.

PMID- 22415408
TI  - Family history and parental recognition of overweight in Croatian children.
AB  - The aim of this study was to evaluate the perception of parents on the weight
      status of their offspring, particularly in relation to a family history of
      obesity and obesity-related illnesses. A cross-sectional study of 1,068 child
      parent dyads sampled at school entry health examination was conducted (median age
      of the child 6.75 years, range 5.7-8.3 years, 50.3 % males). The parental
      perception of the weight status of their child was compared to the body mass
      index (BMI, kilogram per square meter), calculated from measured weight and
      height. Weight status (underweight, normal, overweight, and obese) was defined
      using the United States Centers for Disease Control and Prevention BMI for age
      reference charts. Backward multiple linear regression analysis was used to
      determine possible predictors of parental misclassification of overweight/obese
      children. Among this cohort of children, 12 % were overweight, 10.2 % obese, and
      8.1 % were underweight. Only 24.8 % of obese children and 2.2 % of overweight
      children were considered "overweight" by their parents. A positive family history
      was not significantly associated with parental recognition of overweight.
      Parental misperception of overweight/obese children as being normal was related
      to the child BMI z-score (odds ratio (OR) 0.036; 0.012-0.111) and diabetes in
      family history (OR 3.187; 1.207-8.413). CONCLUSION: The majority of parents did
      not perceive their overweight/obese children as overweight. As having an obese
      family member or one who has suffered from an obesity-related illness does not
      increase the parental ability to recognize overweight in their children,
      strategies to increase public awareness about the importance of one's family
      medical history are needed.

PMID- 22415409
TI  - Efficacy of VeinViewer in pediatric peripheral intravenous access: a randomized
      controlled trial.
AB  - Peripheral venous access in infants and children is technically challenging,
      because their veins are small and located deep in subcutaneous tissue, which
      makes them difficult to palpate or visualize. The VeinViewer(r) (Luminetx
      Corporation, Memphis, TN, USA) is a near-infrared light device that delineates
      the running course of subcutaneous veins. In this study, we investigated whether
      the use of the VeinViewer(r) in infants and children facilitated peripheral
      venous access, especially in difficult cases. This study was a randomized,
      controlled trial of a convenience sample of pediatric patients between the ages
      of 1 month and 16 years who required peripheral venous access in the pediatric
      ward. Prior to randomization, difficult intravenous access (DIVA) score, a four
      variable clinical prediction rule for first-attempt success, was estimated. We
      compared the first-attempt success rates and procedural times between the
      VeinViewer(r) group and a control group. We evaluated 111 patients: 54 in the
      VeinViewer(r) group and 57 in the control group. Patient demographics and factors
      related to the success of vein access were similar for both groups. The overall
      first-attempt success rate was 69.4%: i.e., 77/111 in the VeinViewer(r) group and
      38/57 in the control group, a difference that was not statistically significant.
      However, the first-attempt success rate increased from 5/20 in the control group
      to 14/24 in the VeinViewer(r) group for difficult veins with a DIVA score greater
      than 4 (p=0.026). There were no significant differences in procedural time
      between the two groups. CONCLUSION: The VeinViewer(r) facilitated peripheral
      venous access for pediatric patients with difficult veins, which enhanced first
      attempt success rates.

PMID- 22415411
TI  - Diagnostic accuracy of fine-needle aspiration versus core-needle biopsy for the
      diagnosis of thyroid malignancy in a clinical cohort.
AB  - OBJECTIVES: To retrospectively compare the accuracy of fine-needle aspiration
      (FNA) and core-needle biopsy (CNB) for the diagnosis of thyroid malignancy
      METHODS: We evaluated the results of FNA and CNB in 555 consecutive thyroid
      nodules with final diagnoses (malignancy 318, benign 237). All patients underwent
      FNA and CNB simultaneously for each nodule. We assessed the sensitivity,
      specificity and accuracy of FNA, CNB and FNA/CNB for the diagnosis of thyroid
      malignancy. RESULTS: The sensitivity of FNA, CNB and FNA/CNB for thyroid
      malignancy was 68.6%, 86.8% and 90.6%, specificity 100%, 99.2% and 99.2%, and
      accuracy 82.0%, 92.1% and 94.2%, respectively. The sensitivity and accuracy of
      CNB or FNA/CNB for thyroid malignancy were significantly higher than those of FNA
      (P < 0.001). Compared with CNB alone, FNA/CNB was more accurate for thyroid
      malignancy only in small nodules less than 1 cm (P < 0.001). CONCLUSIONS: Our
      clinical cohort data demonstrated that CNB was more accurate for the diagnosis of
      thyroid malignancy than FNA, and FNA/CNB was more accurate than CNB alone in
      small thyroid nodules. CNB will play a complementary role in optimal surgical
      decision-making and the management of thyroid nodules. KEY POINTS: * CNB was more
      accurate for the diagnosis of malignancy than FNA. * Combined FNA/CNB was more
      accurate than CNB alone in small thyroid nodules. * CNB should play at least a
      complementary role in managing thyroid nodules.

PMID- 22415410
TI  - Precise measurement of renal filtration and vascular parameters using a two
      compartment model for dynamic contrast-enhanced MRI of the kidney gives realistic
      normal values.
AB  - OBJECTIVE: To model the uptake phase of T(1)-weighted DCE-MRI data in normal
      kidneys and to demonstrate that the fitted physiological parameters correlate
      with published normal values. METHODS: The model incorporates delay and
      broadening of the arterial vascular peak as it appears in the capillary bed, two
      distinct compartments for renal intravascular and extravascular Gd tracer, and
      uses a small-vessel haematocrit value of 24%. Four physiological parameters can
      be estimated: regional filtration K ( trans ) (ml min(-1) [ml tissue](-1)),
      perfusion F (ml min(-1) [100 ml tissue](-1)), blood volume v ( b ) (%) and mean
      residence time MRT (s). From these are found the filtration fraction (FF; %) and
      total GFR (ml min(-1)). Fifteen healthy volunteers were imaged twice using
      oblique coronal slices every 2.5 s to determine the reproducibility. RESULTS:
      Using parenchymal ROIs, group mean values for renal biomarkers all agreed with
      published values: K ( trans ): 0.25; F: 219; v ( b ): 34; MRT: 5.5; FF: 15; GFR:
      115. Nominally cortical ROIs consistently underestimated total filtration (by
      ~50%). Reproducibility was 7-18%. Sensitivity analysis showed that these fitted
      parameters are most vulnerable to errors in the fixed parameters kidney T(1),
      flip angle, haematocrit and relaxivity. CONCLUSIONS: These renal biomarkers can
      potentially measure renal physiology in diagnosis and treatment. KEY POINTS: *
      Dynamic contrast-enhanced magnetic resonance imaging can measure renal function.
      * Filtration and perfusion values in healthy volunteers agree with published
      normal values. * Precision measured in healthy volunteers is between 7 and 15%.

PMID- 22415412
TI  - The Breast Imaging Reporting and Data System (BI-RADS) in the Dutch breast cancer
      screening programme: its role as an assessment and stratification tool.
AB  - OBJECTIVES: To assess the suitability of the Breast Imaging Reporting and Data
      System (BI-RADS) as a quality assessment tool in the Dutch breast cancer
      screening programme. METHODS: The data of 93,793 screened women in the Amsterdam
      screening region (November 2005-July 2006) were reviewed. BI-RADS categories,
      work-up, age, final diagnosis and final TNM classification were available from
      the screening registry. Interval cancers were obtained through linkage with the
      cancer registry. BI-RADS was introduced as a pilot in the Amsterdam region before
      the nationwide introduction of digital mammography (2009-2010). RESULTS: A total
      of 1,559 women were referred to hospital (referral rate 1.7 %). Breast cancer was
      diagnosed in 485 women (detection rate 0.52 %); 253 interval cancers were
      reported, yielding a programme sensitivity of 66 % and specificity of 99 %. BI
      RADS 0 had a lower positive predictive value (PPV, 14.1 %) than BI-RADS 4 (39.1
      %) and BI-RADS 5 (92.9 %; P < 0.0001). The number of invasive procedures and
      tumour size also differed significantly between BI-RADS categories (P < 0.0001).
      CONCLUSION: The significant differences in PPV, invasive procedures and tumour
      size match with stratification into BI-RADS categories. It revealed inter
      observer variability between screening radiologists and can thus be used as a
      quality assessment tool in screening and as a stratification tool in diagnostic
      work-up. KEY POINTS: * The BI-RADS atlas is widely used in breast cancer
      screening programmes. * There were significant differences in results amongst
      different BI-RADS categories. * Those differences represented the radiologists'
      degree of suspicion for malignancy, thus enabling stratification of referrals. *
      BI-RADS can be used as a quality assessment tool in screening. * Training should
      create more uniformity in applying the BI-RADS lexicon.

PMID- 22415413
TI  - Abdominal fat distribution on computed tomography predicts ureteric calculus
      fragmentation by shock wave lithotripsy.
AB  - OBJECTIVES: To assess the effects of abdominal fat on shock wave lithotripsy
      (SWL). We used pre-SWL unenhanced computed tomography (CT) to evaluate the impact
      of abdominal fat distribution and calculus characteristics on the outcome of SWL.
      METHODS: One hundred and eighty-five patients with a solitary ureteric calculus
      treated with SWL were retrospectively reviewed. Each patient underwent unenhanced
      CT within 1 month before SWL treatment. Treatment outcomes were evaluated 1 month
      later. Unenhanced CT parameters, including calculus surface area, Hounsfield unit
      (HU) density, abdominal fat area and skin to calculus distance (SSD) were
      analysed. RESULTS: One hundred and twenty-eight of the 185 patients were found to
      be calculus-free following treatment. HU density, total fat area, visceral fat
      area and SSD were identified as significant variables on multivariate logistic
      regression analysis. The receiver-operating characteristic analyses showed that
      total fat area, para/perirenal fat area and visceral fat area were sensitive
      predictors of SWL outcomes. CONCLUSION: This study revealed that higher
      quantities of abdominal fat, especially visceral fat, are associated with a lower
      calculus-free rate following SWL treatment. Unenhanced CT is a convenient
      technique for diagnosing the presence of a calculus, assessing the intra
      abdominal fat distribution and thereby helping to predict the outcome of SWL. KEY
      POINTS: * Unenhanced CT is now widely used to assess ureteric calculi. * The same
      CT protocol can provide measurements of abdominal fat distribution. * Ureteric
      calculi are usually treated by shock wave lithotripsy (SWL). * Greater intra
      abdominal fat stores are generally associated with poorer SWL results.

PMID- 22415415
TI  - Immuno-like assays and biomimetic microchips.
AB  - Biomimetic assays with molecularly imprinted polymers (MIPs) are bound to be an
      alternative to the traditional immuno-analytical methods based on antibodies.
      This is due to the unique combination of advantages displayed by the artificial
      materials including the absence of animal inoculation and sacrifice, unnecessary
      hapten conjugation to a carrier protein for stimulated production, the
      possibility of manufacturing MIPs against toxic substances, excellent
      physicochemical stability, reusability, ease of storage, and recognition in
      organic media. If the selectivity and affinity of MIPs are increased, many more
      immuno-like assays will be developed using radioactive, enzymatic, colorimetric,
      fluorescent, chemiluminescent, or electrochemical interrogation methods. This
      chapter provides a comprehensive comparison between the bio- and biomimetic
      entities and their usage.

PMID- 22415414
TI  - Lung cancer perfusion: can we measure pulmonary and bronchial circulation
      simultaneously?
AB  - OBJECTIVE: To describe a new CT perfusion technique for assessing the dual blood
      supply in lung cancer and present the initial results. METHODS: This study was
      approved by the institutional review board. A CT protocol was developed, and a
      dual-input CT perfusion (DI-CTP) analysis model was applied and evaluated
      regarding the blood flow fractions in lung tumours. The pulmonary trunk and the
      descending aorta were selected as the input arteries for the pulmonary
      circulation and the bronchial circulation respectively. Pulmonary flow (PF),
      bronchial flow (BF), and a perfusion index (PI, = PF/ (PF + BF)) were calculated
      using the maximum slope method. After written informed consent was obtained, 13
      consecutive subjects with primary lung cancer underwent DI-CTP. RESULTS:
      Perfusion results are as follows: PF, 13.45 +/- 10.97 ml/min/100 ml; BF, 48.67 +/
      28.87 ml/min/100 ml; PI, 21 % +/- 11 %. BF is significantly larger than PF, P <
      0.001. There is a negative correlation between the tumour volume and perfusion
      index (r = 0.671, P = 0.012). CONCLUSION: The dual-input CT perfusion analysis
      method can be applied successfully to lung tumours. Initial results demonstrate a
      dual blood supply in primary lung cancer, in which the systemic circulation is
      dominant, and that the proportion of the two circulation systems is moderately
      dependent on tumour size. KEY POINTS: A new CT perfusion technique can assess
      lung cancer's dual blood supply. A dual blood supply was confirmed with dominant
      bronchial circulation in lung cancer. The proportion of the two circulations is
      moderately dependent on tumour size. This new technique may benefit the
      management of lung cancer.

PMID- 22415416
TI  - Chromatography, solid-phase extraction, and capillary electrochromatography with
      MIPs.
AB  - Most analytical applications of molecularly imprinted polymers are based on their
      selective adsorption properties towards the template or its analogs. In
      chromatography, solid phase extraction and electrochromatography this adsorption
      is a dynamic process. The dynamic process combined with the nonlinear adsorption
      isotherm of the polymers and other factors results in complications which have
      limited the success of imprinted polymers. This chapter explains these problems
      and shows many examples of successful applications overcoming or avoiding the
      problems.

PMID- 22415417
TI  - Microgels and nanogels with catalytic activity.
AB  - Molecular imprinting has grown considerably over the last decade with more and
      more applications being developed. The use of this approach for the generation of
      enzyme-mimics is here reviewed with a particular focus on the most recent
      achievements using different polymer formats such as microgels and nanogels,
      beads, membranes and also silica nanoparticles.

PMID- 22415418
TI  - Interaction of vanadium oxide cluster anions with water: an experimental and
      theoretical study on reactivity and mechanism.
AB  - Vanadium oxide cluster anions (V(x)O(y)(-), x = 2-3; y = 3-7) are produced by
      laser ablation and reacted with water in a fast flow reactor. A time-of-flight
      mass spectrometer is used to detect the cluster distribution before and after the
      reactions. Reaction channels of molecular hydrogen elimination (for V(2,3)O(3)(
      )), water association (for V(2)O(5)(-) and V(3)O(6,7)(-)) and the coexistence of
      both channels (for V(2)O(4)(-) and V(3)O(4,5)(-)) are observed. V(2)O(6)(-) and
      V(3)O(8)(-) are nearly inert toward water. Density functional theory (DFT)
      calculations are performed to study the reaction mechanism of V(2)O(3)(-) in
      different spin states with water and the results support the experimental
      observation. The reaction mechanism of V(2)O(3)(+) with water is also studied,
      which is in agreement with the experimental report in previous literature [Eur.
      J. Inorg. Chem., 2008, 4961] that molecular hydrogen elimination is a minor
      reaction channel for V(2)O(3)(+) + H(2)O. The influence of cluster charge states
      and oxidation states of vanadium atoms on the cluster reactivity are presented
      based on the experimental and theoretical studies.

PMID- 22415419
TI  - Effectiveness of sentinel lymph node intraoperative examination in 753 women with
      breast cancer: are we overtreating patients?
AB  - OBJECTIVE: The goal of our study was to evaluate the sensitivity and specificity
      of sentinel lymph node biopsy (SLNB) frozen section (FS) examinations to detect
      metastatic lymph nodes and also its potential role in avoiding unnecessary
      demolitive axillary surgery. BACKGROUND: SLNB is the standard of care in surgical
      oncology of the breast. Intraoperative evaluation of the SLN seems to achieve
      sufficient sensitivity for macrometastasis (Ma), leading to axillary lymph node
      dissection (ALND) only when strictly necessary. Is it equally as clear when to
      perform ALND if micrometastasis (Mi) or isolated tumor cells (ITCs) are detected?
      METHODS: All consecutive patients from January 2005 to September 2010 operated on
      for breast cancer were prospectively enrolled. All patients underwent an FS SLNB.
      The sensitivity and specificity of SLN FSs in detecting Ma, Mi, and ITCs was
      calculated. All patients with Ma or Mi at FS underwent ALND. For all patients who
      underwent ALND, the number of metastatic non-SLNs was recorded and correlated to
      the size of the SLN metastasis. RESULTS: A total of 753 patients were enrolled.
      FS examination had an overall 54% sensitivity and 100% specificity in detecting
      metastatic disease (Ma/Mi/ITCs). The sensitivity rises to 89% if only Mas were
      considered and to 64% if Mas and Mis were counted together. All patients with Mas
      or Mis detected at FS had a completion ALND during the same procedure (156/222).
      All patients with Mas detected at final pathology (16 false negatives, 2.6%) and
      50 women with Mis or ITCs (119 false negatives, 20%) underwent a delayed ALND.
      When Mis or ITCs were detected in the SLN, only 8 of 73 (10.9%) and none of 4
      (0%) patients, respectively, had at least 1 metastatic non-SLN after ALND. Two
      patients (2/460, 0.43%) who had negative SLNs showed local axillary recurrence.
      After a mean follow-up of 32 months, none of the 71 patients with Mis or ITCs who
      did not undergo a second operation showed local recurrence. CONCLUSIONS: SLNB FS
      is highly effective in detecting the subgroup of patients who may benefit from
      completion ALND during the same surgical procedure. The role of Mi/ITCs in the
      SLN(s) is still unclear, but our data lean toward a less aggressive surgical
      approach.

PMID- 22415420
TI  - Relapse-free survival in patients with nonmetastatic, surgically resected
      pancreatic neuroendocrine tumors: an analysis of the AJCC and ENETS staging
      classifications.
AB  - BACKGROUND: The risk of metastatic spread among patients with early-stage
      pancreatic neuroendocrine tumors has not been well established. The authors
      sought to evaluate whether the new TNM staging systems proposed by the American
      Joint Committee on Cancer (AJCC) and European Neuroendocrine Tumor Society
      (ENETS) are prognostic for relapse-free survival (RFS) after surgical resection.
      METHODS: Patients with surgically resected localized or locally advanced
      pancreatic NETs treated at the H. Lee Moffitt Cancer Center between 1999 and 2010
      were assigned a stage (I-III) based on the AJCC and ENETS classifications. RFS
      and overall survival were measured using Kaplan-Meier methodology, with log-rank
      testing for evaluation of the 2 tumor staging systems. Multivariate analysis was
      performed controlling for tumor grade, location, surgery type, functional
      hormonal status, and incidental diagnosis. RESULTS: The authors identified 123
      patients with nonmetastatic, surgically resected pancreatic NETs. When using the
      AJCC classification, 5-year RFS rates for stages I through III were 78%, 53%, and
      33%, respectively (P < 0.01). Using the ENETS classification, 5-year RFS rates
      for stages I to III were 100%, 70%, and 53% (P < 0.18). When excluding patients
      who were referred after their metastatic recurrence, the 5-year RFS rates for
      stages I to III were 90%, 73%, and 66% according to the AJCC classification, and
      100%, 84%, and 75% according to the ENETS classification. Recurrence rates peaked
      at approximately 2 years after surgery. CONCLUSIONS: The AJCC and ENETS TNM
      classifications for pancreatic NETs are prognostic for recurrence-free survival
      and can be adopted in clinical practice.

PMID- 22415421
TI  - Long-term follow-up of malignancy biomarkers in patients with Barrett's esophagus
      undergoing medical or surgical treatment.
AB  - OBJECTIVE: This study aims to compare some validated biomarkers of malignancy (Ki
      67, p53, and apoptosis) between 2 groups of patients with Barrett's esophagus
      (BE) undergoing randomly medical or surgical treatment. BACKGROUND: The treatment
      of choice to prevent the malignant progression of BE remains controversial.
      Translational studies using biomarkers associated with the metaplasia-tumor
      pathway could be useful to provide some information in this regard. METHODS: The
      study group consisted of 45 patients: 20 under medical treatment with 40 mg/day
      of proton pump inhibitors (PPIs) and 25 after Nissen fundoplication (NFP). After
      a median follow-up of 8 years (range, 5-10 years), the values of Ki-67, p53, and
      apoptosis were analyzed in all patients before treatment (n = 45) and then 1 year
      (n = 45), 3 years (n = 45), 5 years (n = 45), and 10 years (n = 25) afterwards in
      both groups of treatment. These values were also analyzed in 2 subgroups of
      patients with successful medical and surgical treatment. RESULTS: Both Ki-67 and
      p53 remained stable after NFP, whereas they increased progressively in patients
      under PPIs with statistically significant differences between the 2 groups.
      Conversely, the apoptotic index increased progressively after NFP and decreased
      in the patients under PPIs with significant differences at 3, 5, and 10 years of
      follow-up. On comparing the subgroups of successful treatment the same
      differences were found. CONCLUSIONS: Barrett's epithelium remains more stable
      after a long-term follow-up in patients with BE treated surgically than in those
      under PPIs even in the absence of abnormal rates of acid reflux.

PMID- 22415422
TI  - Evaluation study of different strategies for detecting surgical site infections
      using the hospital information system at Lyon University Hospital, France.
AB  - OBJECTIVE: To evaluate different strategies for detecting surgical site
      infections (SSIs) using different sources (notification by the surgeon,
      bacteriological results, antibiotic prescription, and discharge diagnosis codes).
      BACKGROUND: Surveillance plays a role in reducing the risks of SSIs but the
      performance of case reports by surgeons is insufficient. Indirect methods of SSI
      detection are an alternative to increase the quality of surveillance. METHODS: A
      retrospective cohort study of 446 patients operated consecutively during the
      first half of 2007 was set up in a 56-bed general surgery unit in Lyon University
      Hospital, France. Patients were followed up 30 days after intervention. Different
      methods of detection were established by combining different data sources. The
      sensitivity and specificity of these methods were calculated by using, as
      reference method, the manual review of the medical records. RESULTS: The
      sensitivity and specificity of SSI detection were, respectively, 18.4% (95%
      confidence interval [CI]: 7.9-31.6) and 100% for surgeon notification; 63.2% (95%
      CI: 47.3-78.9) and 95.1% (95% CI: 92.9-97.1) for detection based on positive
      cultures; 68.4% (95% CI: 52.6-81.6) and 87.5% (95% CI: 84.3-90.7) using
      antibiotic prescription; 26.3% (95% CI: 13.2-42.1) and 99.5% (95% CI: 98.8-100)
      using discharge diagnosis codes. By combining the latter 3 sources, the
      sensitivity increased at 86.8% (95% CI: 76.3-97.4) and the specificity was
      lowered at 85.5% (95% CI: 82.1-89.0). CONCLUSIONS: SSI detection based on the
      combination of data extracted automatically from the hospital information system
      performed well. This strategy has been implemented gradually in Lyon University
      Hospital.

PMID- 22415423
TI  - Congruence of primary brain tumor patient and caregiver symptom report.
AB  - BACKGROUND: Evaluating the severity of symptoms in patients with primary brain
      tumors (PBTs) is important in clinical care and research but may be difficult due
      to patient neurocognitive (NC) impairment. This study was conducted to evaluate
      the congruence of symptom reporting in patient and caregiver dyads, examining
      potential impact of NC impairment and Karnofsky performance status (KPS).
      METHODS: PBT patients undergoing NC testing and their caregivers were included in
      this study. These dyads (paired patient and caregiver group) completed the MD
      Anderson Symptom Inventory-Brain Tumor Module prior to testing, and impairment
      was categorized based on NC test scores. Concordance and equivalency was then
      assessed using Bland-Altman analysis and 2 one-sided techniques. RESULTS: A total
      of 115 dyads participated. Median patient and caregiver age was 49 and 51 years,
      respectively, and 63% of patients were male (73% female caregivers). Most
      patients had a good KPS (>=90, 66%) but were classified as NC impaired (58%).
      Caregiver's report of patient symptoms are congruent to the self-report of the
      patient. Equivalency between patient and caregiver report were found using
      prespecified confidence intervals. KPS group (good, >=90; poor, <=80) comparisons
      of equivalency indicated no significant differences in symptoms and interference
      reporting between dyads (good = 0.49, P > .05; and poor = 0.3, P > .05) overall,
      but there was a tendency for higher report by caregivers if the patients had a
      poor KPS. CONCLUSIONS: Caregivers of PBT patients have similar assessments of
      symptom severity (highly congruent) with patient self-report regardless of NC
      function or KPS. These findings suggest that caregivers may serve as proxy report
      of symptoms for primary brain tumor patients.

PMID- 22415424
TI  - Theoretical analysis of the conversion mechanism of acetylene to ethylidyne on
      Pt(111).
AB  - The conversion of acetylene to ethylidyne on Pt(111) has been comprehensively
      investigated using self-consistent periodic density functional theory. Geometries
      and energies for all of the intermediates involved as well as the conversion
      mechanism were analyzed. On Pt(111), the carbon atoms in the majority of stable
      C(2)H(x) (x = 1-4) intermediates prefer saturated sp(3) configurations with the
      missing H atoms substituted by the adjacent metal atoms. The most favorable
      conversion pathway for acetylene to ethylidyne is via a three-step reaction
      mechanism, acetylene -> vinyl -> vinylidene -> ethylidyne. The first step,
      acetylene -> vinyl, depends on the availability of surface H atoms: without
      preadsorbed H the reaction occurs via the initial disproportionation of
      acetylene, which resulted in adsorbed vinyl; with an abundance of preadsorbed H,
      acetylene could transform to vinyl via both the disproportionation and
      hydrogenation reactions. Conversions through initial dehydrogenation of acetylene
      and isomerizations of acetylene and vinyl are unfavorable due to high energy
      barriers along the relevant pathways. The conversion rate involving vinylidene as
      an intermediate is at least 100 times larger than that involving ethylidene.

PMID- 22415425
TI  - Generalized linear mixed models for mapping multiple quantitative trait loci.
AB  - Many biological traits are discretely distributed in phenotype but continuously
      distributed in genetics because they are controlled by multiple genes and
      environmental variants. Due to the quantitative nature of the genetic background,
      these multiple genes are called quantitative trait loci (QTL). When the QTL
      effects are treated as random, they can be estimated in a single generalized
      linear mixed model (GLMM), even if the number of QTL may be larger than the
      sample size. The GLMM in its original form cannot be applied to QTL mapping for
      discrete traits if there are missing genotypes. We examined two alternative
      missing genotype-handling methods: the expectation method and the overdispersion
      method. Simulation studies show that the two methods are efficient for multiple
      QTL mapping (MQM) under the GLMM framework. The overdispersion method showed
      slight advantages over the expectation method in terms of smaller mean-squared
      errors of the estimated QTL effects. The two methods of GLMM were applied to MQM
      for the female fertility trait of wheat. Multiple QTL were detected to control
      the variation of the number of seeded spikelets.

PMID- 22415426
TI  - Trapeziectomy and tendon suspension with or without a mitek anchor fixation in
      the thumb basal joint osteoarthritis.
AB  - Partial trapeziectomy with suspension ligamentoplasty is a commonly performed
      treatment of thumb osteoarthritis. Nevertheless, the post-operative recovery
      remains long and critical reason for which different modifications of the
      surgical technique have been proposed. To compare two suspension ligamentoplasty
      techniques, one with a mitek anchor and another without, a retrospective study of
      55 consecutive operated patients was performed. A detailed clinical analysis of
      pain, function and a radiologic assessment of the trapeziometacarpal space were
      performed. Mitek anchor fixation was associated with a shorter convalescence
      period. However, in spite of an improved radiological maintenance of the
      scaphometacarpal space, mitek anchor fixation was associated with an impaired
      postoperative function and residual pain when compared with the conventional
      suspension ligamentoplasty procedure. Patient's satisfaction was comparable in
      both groups. In our series stabilization of the suspension ligamentoplasty
      procedure by the insertion of a mitek anchor did not bring the hoped benefits to
      the patients with a trapeziometacarpal arthritis.

PMID- 22415427
TI  - Perineural fat grafting in the treatment of painful end-neuromas of the upper
      limb: a pilot study.
AB  - The purpose of this study was to evaluate the effectiveness and middle-term
      durability of the results achieved with perineural fat grafting of painful
      neuromas of the upper limb. We retrospectively analysed eight patients, affected
      by eight neuromas, treated by neuroma excision and fat grafting around the
      proximal nerve stump. Clinical parameters, the disabilities of the arm shoulder
      and hand score, and the visual analogue scale were recorded at 2, 6 and 12 months
      after surgery. A reduction of 23.2% was observed in the mean disabilities of the
      arm shoulder and hand scores at 12 months. The spontaneous baseline visual
      analogue scale score showed a mean improvement of 22% at 12 months, although not
      this was not statistically significant. Perineural fat grafting is a quick and
      useful procedure and could represent a useful primary operation in the treatment
      of pain syndromes of neuropatic origin.

PMID- 22415428
TI  - Metachronous Mycobacterium terrae complex tenosynovitis of the hand.

PMID- 22415429
TI  - Dorsal scapholunate ligament injury: a classification of clinical forms.
AB  - The dorsal scapholunate (SL) ligament may disrupt in variety of ways. Each form
      of injury requires specific fixation. To investigate the incidence of each type
      of ligament failure, the records of 45 patients with adequate information, good
      quality pictures, or videos demonstrating injury characteristics were reviewed.
      Four types of SL injury were found: type 1 (lateral avulsion from the scaphoid)
      was the most frequent, present in 19 patients (42%); type 2 (medial avulsion from
      the lunate) was the least frequent, with 7 cases (16%); type 3 (mid-substance
      rupture) was found on 9 occasions (20%); and type 4 (partial rupture plus
      elongation) was observed on 10 occasions (22%). Based on our observations, we
      submit that an arthroscopically assisted SL capsuloplasty may not be possible in
      all cases, particularly not when the ligament has avulsed off the bone (60% of
      the cases), leaving no ligament remnant on one side. Most patients will require
      ligament reattachment techniques using transosseous sutures, bone anchors, or
      ligament reconstruction.

PMID- 22415430
TI  - Nasopharyngeal carcinoma with hand metastasis.

PMID- 22415431
TI  - Iatrogenic ulna fracture following Kirschner wire fixation of a distal radius
      fracture in a 98-year-old lady.

PMID- 22415433
TI  - LaOF:Eu3+ nanocrystals: hydrothermal synthesis, white and color-tuning emission
      properties.
AB  - Uniform LaOF and LaOF : Eu(3+) nanocrystals of the gamma-form have been
      successfully synthesized under mild conditions via a facile hydrothermal method
      followed a heat treatment of their bastnaesite-type precursor (LaCO(3)F). The
      synthetic details, investigations into the phase purity and the presence of the
      oxocarbonate anion CO(3)(2-) proven by IR measurements and EDX, as well as X-ray
      powder diffraction data, are given. Photoluminescence (PL) and
      cathodoluminescence (CL) spectra were utilized to characterize the luminescence
      properties of the LaCO(3)F : Eu(3+) and LaOF : Eu(3+) samples. Under ultraviolet
      light excitation, the LaCO(3)F : Eu(3+) precursor shows an orange emission of
      Eu(3+) (dominated by (5)D(0)->(7)F(1)), while the product of heat treatment, LaOF
      : Eu(3+), shows the characteristic emissions of Eu(3+) ((5)D(J)->(7)F(J')J, J' =
      0, 1, 2, 3 transitions). Under the excitation of UV and low-voltage electron
      beams, the emission color (including white) of LaOF : Eu(3+) can be tuned by
      adjusting the doping concentration of Eu(3+). The corresponding luminescence
      mechanisms have been discussed in detail.

PMID- 22415432
TI  - Enhanced peripheral gammadeltaT cells cytotoxicity potential in patients with HBV
      associated acute-on-chronic liver failure might contribute to the disease
      progression.
AB  - BACKGROUND: The current study explored the characteristics of gammadelta T cells
      in the blood of HBV-associated acute-on-chronic liver failure (HBV-ACLF) patients
      and examined the relationship between gammadelta T cells and the clinical
      parameters. METHODS: Blood samples were obtained from 26 patients with HBV-ACLF,
      40 patients with chronic hepatitis B virus (HBV) infection (CHBV), and 25 healthy
      controls (HC). The frequencies of gammadelta T cells, subtype Vdelta1T or
      Vdelta2T, and CD45RO(+)gammadelta T cells were determined using flow cytometry.
      Intracellular cytokine staining analysis was used to evaluate the proportion of
      the IFN-gamma-, TNF-alpha-, or IL-17-producing gammadelta T cells, and CD107a- or
      granzyme B-positive gammadelta T cells. RESULTS: We found that the proportion of
      gammadelta T cells in blood samples from HBV-ACLF patients was much lower than in
      samples from CHBV patients or healthy controls. After stimulation with PMA and
      ionomycin, gammadelta T cells from HBV-ACLF patients produced the greatest amount
      of TNF-alpha or IL-17 among the three groups. Granzyme B- or CD107a-positive
      gammadelta T cells were significantly more frequent than in CHBV or control
      samples. There was a negative correlation between the percent of TNF
      alpha(+)gammadelta T cells and ALT or AST levels, and between the percent of
      CD107a(+)gammadelta T cells and TBiL or DBiL levels. CONCLUSIONS: These results
      suggest that gammadelta T cells might participate in liver injury in HBV-ACLF
      patients by producing increased amounts of inflammatory cytokines and/or
      cytotoxicity ability. These findings provide novel information regarding the
      pathogenesis of HBV-ACLF.

PMID- 22415435
TI  - Mortality and morbidity of nosocomial respiratory syncytial virus (RSV) infection
      in ventilated children--a ten year perspective.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is one of the most common pathogens
      involved in nosocomial infection in children. The aim of the study was to
      determine the impact of nosocomial RSV infection on mortality and pediatric
      intensive care unit (PICU) morbidity of ventilated children. METHODS: This is a
      prospective observational cohort study of all children ventilated with RSV
      infection in a tertiary-referral PICU over a 10-year period. Determinants of the
      relationship of nosocomial (PICU-acquired and hospital ward-acquired) RSV
      infection to mortality and PICU morbidity were adjusted for by performing
      multiple regression analysis. RESULTS: Of 525 RSV-positive children ventilated on
      PICU during the ten-year study period, 38 (7.2%) acquired their RSV infection
      following PICU admission and 38 (7.2%) had acquired RSV in hospital. Ten (26%)
      children that acquired RSV on PICU died (RR 6.4, 95%CI 3.2-12.9) and 11 (29%)
      with hospital ward-acquired infection died (RR 9.8, 95%CI 5.1-18.9), compared to
      18 (4%) with community-acquired RSV infection. Nosocomial RSV infection was
      significantly and independently associated with death which was more strongly
      predicted by immunodeficiency and congenital heart disease (P<0.01). Nosocomial
      RSV infection was the strongest predictor for morbidity as reflected in duration
      of ventilation and length of stay on PICU (P<0.01). CONCLUSION: Nosocomial RSV
      infection was independently associated with increased mortality and was the
      strongest predictor of duration of ventilation and length of stay in children on
      PICU. Decreasing nosocomial RSV infection would reduce deaths in ventilated
      children.

PMID- 22415436
TI  - Post-hoc revision of the pediatric anesthesia emergence delirium rating scale:
      clinical improvement of a bedside-tool?
AB  - BACKGROUND: Pediatric delirium (PD) is a severe neuropsychiatric disorder often
      seen at the pediatric intensive care unit (PICU). The Pediatric Anesthesia
      Emergence Delirium (PAED) scale assesses five behavioral items on a five-level
      severity scale, and is easily applicable in children. However, the five-level
      severity scales are rather arbitrarily anchored and subjective. This study aimed
      to pilot a practical and clinical improvement of the PAED by condensing the five
      level scales of the five behavioral items to a more objectively anchored two- and
      three-point scale. METHODS: Post-hoc analysis of routine data in an eight-bed
      PICU in a tertiary university hospital. 144 critically ill, non-electively
      admitted patients, aged 1-18 years, were included between November 2006 and
      February 2010. Scales of the five PAED-items were condensed post-hoc from five to
      two- and three levels of severity. Five scale properties were analyzed: 1)
      internal consistency; 2) item-total score correlations; 3) inter-rater agreement;
      4) sensitivity and specificity; and 5) discriminative diagnostic ability.
      RESULTS: Three-level PAED-items post-hoc displayed Cronbach's alpha of 0.86, and
      mean item-total score correlation was 0.71 (range 0.60 to 0.79). Inter-rater
      agreement was high (0.90). The most optimal cut-off was 8 (sensitivity=100%,
      specificity=96.7%) with an area under the curve (AUC) of 0.98. Likelihood ratio
      for a positive test result (LR+) was 30.3. CONCLUSION: A three-level severity
      scale for the five PAED-items may be optimal to diagnose PD. Further prospective
      research is required to determine whether a revised PAED has adequate
      psychometric properties and is applicable across different clinical settings.

PMID- 22415437
TI  - Anesthetic concerns for robotic-assisted laparoscopic radical prostatectomy.
AB  - The anesthetic concerns of patients undergoing robotic-assisted laparoscopic
      radical prostatectomy (RALP) are primarily related to the use of pneumoperitoneum
      in the steep Trendelenburg position. This combination will affect
      cerebrovascular, respiratory and hemodynamic homeostasis. Possible non-surgical
      complications range from mild subcutaneous emphysema to devastating ischemic
      optic neuropathy. The anesthetic management of RALP patients involves a thorough
      preoperative evaluation, careful positioning on the operative table, managing
      ventilation issues, and appropriate fluid management. Close coordination between
      the anesthesia and surgical teams is required for a successful surgery. This
      review will discuss the anesthetic concerns and perioperative management of
      patients presenting for RALP.

PMID- 22415438
TI  - Hemorrhagic shock resulting in cardiac arrest: is therapeutic hypothermia
      contraindicated?

PMID- 22415439
TI  - Comparison of conventional radiography combined with ultrasonography versus
      nonenhanced helical computed tomography in evaluation of patients with renal
      colic.
AB  - The aim of this study is to determine whether kidneys ureters bladder X-ray (KUB)
      film combined with ultrasound (US) can be effectively used in evaluation of renal
      colic and miss stones with clinically significant size identified on nonenhanced
      computed tomography (NECT) in patients with urolithiasis. This retrospective
      study evaluated the clinical and radiological records of 300 patients at our
      institution undergoing KUB and/or US and/or NECT for the evaluation of renal
      colic from June 2007 to December 2010. Of patients with negative findings on KUB
      and/or US, 22 had renal stones on NECT (mean size 4.4 mm, range 3-8), 3 had lower
      ureteral stone (mean size 3.3 mm, range 2-5). In patients with isolated
      suspicious renal ectasia without stone image, two had renal stone on NECT (mean
      size 4 mm, range 2-6), 5 had upper ureteral stone (mean size 4.4 mm, range 4-6),
      7 had middle ureteral stone (mean size 3.7 mm, range 3-4) and 14 had lower
      ureteral stone (mean size 4 mm, range 2-6). The cost-effective and almost
      radiation-free combination of KUB and US should be preferred for diagnosis of
      urolithiasis, as it detects most of the ureteral and renal calculi which are
      clinically significant.

PMID- 22415440
TI  - Evaluation of surgical outcomes of retro-rectus versus intraperitoneal
      reinforcement with bio-prosthetic mesh in the repair of contaminated ventral
      hernias.
AB  - INTRODUCTION: Hernia repairs in contaminated fields are often reinforced with a
      bioprosthetic mesh. When choosing which of the multiple musculofascial abdominal
      wall planes provides the most durable repair, there is little guidance. We
      hypothesized that the retro-rectus plane would reduce recurrence rates versus
      intraperitoneal placement due to greater surface area contact of mesh with well
      vascularized tissue. METHODS: Forty-nine of the 80 patients in an ongoing,
      prospective, multicenter study of contaminated ventral hernia repairs (RICH
      study, NCT00617357) achieved fascial closure after musculofascial centralization
      and reinforcement with non-crosslinked porcine acellular dermal matrix
      (StratticeTM, LifeCell, Branchburg, NJ) and were retrospectively analyzed. The
      Strattice was placed in the retro-rectus position in 23 patients and in the
      intraperitoneal position in 26. RESULTS: Subjects were comparable in age,
      obesity, prior wound infection, presence of a stoma, and infected mesh removal (p
      > 0.05). More smokers were present in the intraperitoneal group (p = 0.02). Retro
      rectus defects were significantly wider and had larger area than the
      intraperitoneal repairs. At the 1-year follow-up, 44 (90%) of patients were
      available for review. There was no difference in wound infections, seromas, or
      hematomas. Recurrent hernias were identified in 10% of retro-rectus repairs and
      30% of intraperitoneal repairs (p = 0.14). CONCLUSIONS: In this retrospective
      analysis of a prospective multicenter study of large, contaminated ventral
      hernias, despite a larger hernia defect in the retro-rectus group, placement of
      the mesh in the retro-rectus compartment resulted in a similar recurrence rate to
      intraperitoneal mesh placement. Ongoing evaluation is important to establish
      longer-term outcomes and the validity of these findings.

PMID- 22415441
TI  - Anticoccidial effect of halofuginone hydrobromide against Eimeria tenella with
      associated histology.
AB  - Halofuginone (stenorol) has been used as an effective anticoccidial reagent for
      decades but very little is known about its mode of action. In this study,
      chickens were inoculated with Eimeria tenella oocysts on 14-day-old and medicated
      with halofuginone at days 0, 1, 2, 3, 4, 5 and 6 post inoculations (groups 0, 1,
      2, 3, 4, 5 and 6, respectively). Chickens in group 7 were taken as challenge
      unmedicated control and in group 8 unchallenged-unmedicated control. The survival
      rate, body weight gains (BWG), oocysts production, cecal scores, bloody diarrhea
      and histological examinations were analyzed to evaluate the anticoccidial
      efficacy of halofuginone and to initially elucidate its mechanisms. Results
      showed that halofuginone which acted as a coccidiostatic can significantly
      enhance the BWG, and decrease both the oocyst shedding and cecal destruction
      caused by E. tenella infection. The histological slide examination noted that
      halofuginone was effective when provided 0-2 days post inoculation but only
      partially effective when applied 3-7 days post infection. The second-generation
      schizonts treated with halofuginone appeared vacuolated and degenerated. It is
      concluded that halofuginone can inhibit the parasite's invasion of host cecal
      hypothetical cell at the early stages of life cycle and later disturb the
      parasite's development by vacuolation of the schizonts. The resulting abnormal
      schizonts could not divide into schizoites and were eventually eliminated by the
      host's immune response.

PMID- 22415442
TI  - Abeta toxicity in Alzheimer's disease.
AB  - Alzheimer's Disease (AD), the most common age-related neurodegenerative disorder,
      is characterized by progressive cognitive decline, synaptic loss, the formation
      of extracellular beta-amyloid plaques and intracellular neurofibrillary tangles,
      and neuronal cell death. Despite the massive neuronal loss in the 'late stage' of
      disease, dendritic spine loss represents the best pathological correlate to the
      cognitive impairment in AD patients. The 'amyloid hypothesis' of AD recognizes
      the Abeta peptide as the principal player in the pathological process. Many lines
      of evidence point out to the neurotoxicity of Abeta, highlighting the correlation
      between soluble Abeta oligomer accumulation, rather than insoluble Abeta fibrils
      and disease progression. Pathological increase of Abeta in AD brains, resulting
      from an imbalance between its production, aggregation and clearance, might target
      mitochondrial function promoting a progressive synaptic impairment. The knowledge
      of the exact mechanisms by which Abeta peptide impairs neuronal function will
      help us to design new pharmacological tools for preventing AD neurodegeneration.

PMID- 22415443
TI  - Effect of pesticides on the aggregation of mutant huntingtin protein.
AB  - The classical reports on neurodegeneration concentrate on studying disruption of
      signalling cascades. Although it is now well recognized that misfolding and
      aggregation of specific proteins are associated with a majority of these
      diseases, their role in aggravating the symptoms is not so well understood.
      Huntington's disease (HD) is a neurodegenerative disorder that results from
      damage to complex II of mitochondria. In this work, we have studied the effect of
      mitochondrial complex I inhibitors, viz. 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine and rotenone, and complex II inhibitor, viz. 3-nitropropionic
      acid, on the aggregation of mutant huntingtin (mthtt) protein, whose misfolding
      and aggregation results in cellular abnormalities characteristic of HD. All three
      inhibitors were found to accelerate the aggregation of mthtt in vitro, although
      the amounts of aggregates formed were different in all cases. Thus, apart from
      their effect on mitochondrial viability, these neurotoxins are capable of
      interfering with the protein aggregation process and thus, hastening the onset of
      the disease.

PMID- 22415445
TI  - A novel conjugate of a cell-penetrating peptide and a ferrocenyl amino acid: a
      potential electrochemical sensor for living cells?
AB  - The conjugation of a ferrocenyl amino acid to the cell-penetrating peptide hCT(9
      32) does not impair its ability to efficiently translocate into cells.
      Furthermore, the bioconjugate does not induce any cytotoxicity, thus presenting a
      potential electrochemical sensor suitable for the detection of living cells.

PMID- 22415444
TI  - Anti-proliferative effects of tricyclodecan-9-yl-xanthogenate (D609) involve
      ceramide and cell cycle inhibition.
AB  - Tricyclodecan-9-yl-xanthogenate (D609) inhibits phosphatidylcholine (PC)
      phospholipase C (PLC) and/or sphingomyelin (SM) synthase (SMS). Inhibiting SMS
      can increase ceramide levels, which can inhibit cell proliferation. Here, we
      examined how individual inflammatory and glia cell proliferation is altered by
      D609. Treatment with 100-MUM D609 significantly attenuated the proliferation of
      RAW 264.7 macrophages, N9 and BV-2 microglia, and DITNC(1) astrocytes, without
      affecting cell viability. D609 significantly inhibited BrdU incorporation in BV-2
      microglia and caused accumulation of cells in G(1) phase with decreased number of
      cells in the S phase. D609 treatment for 2 h significantly increased ceramide
      levels in BV-2 microglia, which, following a media change, returned to control
      levels 22 h later. This suggests that the effect of D609 may be mediated, at
      least in part, through ceramide increase via SMS inhibition. Western blots
      demonstrated that 2-h treatment of BV-2 microglia with D609 increased expression
      of the cyclin-dependent kinase (Cdk) inhibitor p21 and down-regulated phospho
      retinoblastoma (Rb), both of which returned to basal levels 22 h after removal of
      D609. Exogenous C8-ceramide also inhibited BV-2 microglia proliferation without
      loss of viability and decreased BrdU incorporation, supporting the involvement of
      ceramide in D609-mediated cell cycle arrest. Our current data suggest that D609
      may offer benefit after stroke (Adibhatla and Hatcher, Mol Neurobiol 41:206-217,
      2010) through ceramide-mediated cell cycle arrest, thus restricting glial cell
      proliferation.

PMID- 22415446
TI  - Action video game experience reduces the cost of switching tasks.
AB  - Video game expertise has been shown to have beneficial effects for visual
      attention processes, but the effects of action video game playing on executive
      functions, such as task switching and filtering out distracting information, are
      less well understood. In the main experiment presented here, video game players
      (VGPs) and nonplayers (nVGPs) switched between two tasks of unequal familiarity:
      a familiar task of responding in the direction indicated by an arrow, and a novel
      task of responding in the opposite direction. nVGPs had large response time costs
      for switching from the novel task to the familiar task, and small costs for
      switching from the familiar task to the novel task, replicating prior findings.
      However, as compared to the nVGPs, VGPs were more facile in switching between
      tasks, producing overall smaller and more symmetric switching costs, suggesting
      that experience with action video games produces improvements in executive
      functioning. In contrast, VGPs and nVGPs did not differ in filtering out the
      irrelevant flanking stimuli or in remembering details of aurally presented
      stories. The lack of global differences between the groups suggests that the
      improved task-switching performance seen in VGPs was not due to differences in
      global factors, such as VGPs being more motivated than nVGPs.

PMID- 22415447
TI  - Cross-modal nonspatial repetition inhibition.
AB  - Although it has been well documented that the spatial inhibitory effect induced
      by repetition of location (i.e., spatial inhibition of return, or IOR) occurs
      cross-modally, we do not yet know whether nonspatial (e.g., color-based)
      repetition-induced inhibition occurs in a cross-modal fashion as well. In the
      present study, a novel cross-modal paradigm with regard to color-based repetition
      was adopted. An intervening neutral cue, whose semantic identity was different
      from those of both the prime and the target, was introduced between the prime and
      the target in a repetition-priming task. The modalities of the prime, the neutral
      cue, and the target could be either visual or auditory, and the prime and the
      target could refer either to the same or to different semantic identities. By
      adopting this paradigm, we aimed to answer two questions: (1) What are the
      specific conditions under which cross-modal semantic-based repetition inhibition
      occurs? (2) Are the representations inhibited in the semantic-based repetition
      inhibition effect supramodal or modality-specific? Our results suggested that
      semantic-based repetition inhibition occurs only when the prime and the neutral
      cue are from the same sensory modality, and it occurs irrespective of whether the
      modality of the target is cued and irrespective of whether the modality of the
      target is auditory or visual. Taken together, our results suggest that the
      occurrence of cross-modal nonspatial repetition inhibition is conditional and
      that the nonspatial representations inhibited by the repetition inhibition are
      supramodal.

PMID- 22415448
TI  - Special issue: 2nd International Symposium on Sustainable Agriculture in Sub
      tropical Regions.

PMID- 22415449
TI  - World fertilizer nutrient reserves: a view to the future.
AB  - The increasing need for food production in subtropical regions likely translates
      to a need for additional plant nutrients. As a consequence, knowledge of world
      fertilizer nutrient reserves is of particular relevance to sustainable
      agriculture in the subtropics. The stewardship responsibilities of agriculture
      include the wise use of the raw materials from which commercial fertilizers are
      produced. Development and implementation of fertilizer best management practices
      with focus on the 4Rs-right source, right rate, right time, right place-are
      timely not only for short-term economic and environmental reasons, but also for
      the wise stewardship of the non-renewable nutrient resources upon which food,
      feed, fiber, and fuel production depend.

PMID- 22415450
TI  - [Non-invasive mechanical ventilation in COPD].
AB  - Non-invasive mechanical ventilation is the preferred method for the treatment of
      acute respiratory failure in patients with chronic obstructive pulmonary disease
      (COPD). Primary contraindications and stopping criteria must be regarded to avoid
      delaying endotracheal intubation. The primary interface is usually a nasal-oral
      mask. Cautious sedation can facilitate non-invasive ventilation in some patients.
      Under certain circumstances non-invasive ventilation may enable successful
      extubation in COPD patients with prolonged weaning. COPD patients can also
      benefit from preventive non-invasive ventilation in order to avoid re-intubation
      after a planned extubation. Domiciliary nocturnal non-invasive ventilation is an
      option for some patients with COPD in chronic hypercapnic respiratory failure.
      This treatment should be established in a specialised unit.

PMID- 22415451
TI  - Paired exchange kidney donation in India: a five-year single-center experience.
AB  - INTRODUCTION: Paired exchange kidney donation (PKD) is an evolving strategy for
      overcoming the barriers that confront patients with end-stage renal disease, when
      the only living potential donors who are willing to donate to them are deemed to
      be unsuitable as donors for them owing to an incompatibility of blood type, of
      HLA cross-match, or of both. In the PKD, the incompatibility problems with two
      donor recipient pairs can be solved by exchanging donors. Although PKD is
      increasing worldwide, we in India have not nearly reached the estimated potential
      of this modality. Herein, we have reported our results with a living donor
      exchange program in past 5 years. MATERIALS AND METHODS: Between March 2006 and
      June 2011, we performed 44 living PKD transplantations. All donor and recipient
      procedures were performed successfully. ABO incompatibility or positive
      lymphocyte cross-match were found in 20 pairs and 2 pairs, respectively. RESULTS:
      The mean recipient age was 42.5 years (range 33-59 years). The mean donor age was
      38 years (range 31-56 years). At a median follow-up of 33 months (range 1-59
      months), graft survival rate was 100 %. All patients have functioning grafts with
      a median serum Creatinine level of 1.13, 1.5, and 1.35 mg/dl at 3 month, 1 year,
      and 3 years, respectively. One patient died after 4 month of transplant due to
      pneumonitis with sepsis. Allograft dysfunction was not seen in any of the
      recipients. CONCLUSION: The PKD transplantation is a viable procedure medically
      and economically, which can be promoted in centers with a low deceased donor
      transplantation rate and a high number of incompatible related donors. We
      achieved excellent graft outcome by using the PKD transplantation program as an
      option to reduce the donor organ shortage.

PMID- 22415452
TI  - [Opacification of a hydrophilic intraocular lens 4 years after cataract surgery.
      A biomaterial analysis].
AB  - Calcification of hydrophilic intraocular lenses (IOL) is a rare complication. We
      report about the uneventful replacement of an opacified hydrophilic IOL. The
      patient presented 4 years after uneventful cataract surgery with a reduction of
      visual acuity due to calcification of the IOL. Macroscopically, the optic and the
      haptics were opacified. Light and scanning electron microscopy revealed granular
      deposits on the external surface of the IOL and numerous fine granular deposits
      within the optic of the IOL which were distributed in a line parallel to the
      surface of the IOL.

PMID- 22415453
TI  - [Iritis with destabilization of the intraocular pressure due to dislocation of a
      posterior chamber intraocular lens].
AB  - This report concerns the case of a 67-year-old male patient who underwent
      uncomplicated phacoemulsification with implantation of a posterior chamber
      intraocular lens (IOL). After an interval of 2 months the patient developed
      iritis together with an uncontrollable increase in intraocular pressure. After a
      detailed examination a dislocated haptic of the IOL was identified as the cause
      of the symptoms. The dislocation had led to uveitis-glaucoma-hyphema syndrome
      although no hemorrhage was observed. In addition to this complication the haptic
      had arroded the zonular complex which made implantation of an anterior chamber
      lens necessary. Although improvements in operating techniques, lens materials and
      designs have been made uveitis-glaucoma-hyphema syndrome has to be kept in mind.
      Surgical intervention is the only therapeutic option.

PMID- 22415454
TI  - Further data supporting that paclitaxel-associated acute pain syndrome is
      associated with development of peripheral neuropathy: North Central Cancer
      Treatment Group trial N08C1.
AB  - BACKGROUND: Paclitaxel causes an acute pain syndrome (P-APS), occurring within
      days after each dose and usually abating within days. Paclitaxel also causes a
      more classic peripheral neuropathy, which steadily increases in severity with
      increasing paclitaxel total doses. Little detail is available regarding the
      natural history of these 2 syndromes, or any relationship between them, although
      a recent publication does provide natural history data about weekly paclitaxel,
      supporting an association between the severity of P-APS and eventual peripheral
      neuropathy symptoms. METHODS: Patients entering this study were about to receive
      paclitaxel and carboplatin every 3 weeks. Daily questionnaires were completed for
      the first week after every chemotherapy dose, and European Organization for
      Research and Treatment of Cancer, Quality of Life Questionnaire, Chemotherapy
      Induced Peripheral Neuropathy 20-item instruments were completed weekly. RESULTS:
      The P-APS severity peaked on day 4 after the initial chemotherapy dose, with 12%,
      29%, 23%, and 36% of patients having maximal pain scores of 0, 1 to 4, 5 or 6, or
      7 to 10 during the first week after the first dose of therapy, respectively.
      Patients with P-APS scores of 0 to 4 with the first dose of chemotherapy had less
      eventual sensory neuropathy than did patients with P-APS scores of 5 to 10 (P =
      0.001). With regard to the more peripheral neuropathy, sensory neuropathy was
      more problematic than was either motor or autonomic neuropathy. Numbness and
      tingling were more common components of the sensory neuropathy than was pain.
      CONCLUSIONS: Patients with worse P-APS severities appear to have more eventual
      chemotherapy-induced peripheral neuropathy. This provides support for the concept
      that P-APS is a form of nerve pathology.

PMID- 22415455
TI  - Recovery effects of hyperoxic gas inhalation or contrast water immersion on the
      postexercise cytokine response, perceptual recovery, and next day exercise
      performance.
AB  - The effect of different recovery modalities on the postexercise cytokine
      response, perceptual recovery, and subsequent day athletic performance were
      investigated. Eight highly trained athletes completed 3 swimming sessions
      consisting of 20 * 200 m efforts, in a counterbalanced repeated-measures design.
      At the conclusion of each session, athletes undertook a 30-minute recovery
      intervention of contrast water therapy (CWT), supplemental oxygen (HYP), or
      passive rest (CON). Venous blood samples were analyzed for levels of interleukin
      6 (IL-6) at the pre-, post-, and 30-minute postswim time points, and a rating of
      perceived recovery was recorded at the conclusion of the 30-minute intervention
      and upon returning to the pool 12 hour later. Finally, a 200-m swim time trial
      was completed as a measure of next day performance. The results showed that there
      was a significant increase in IL-6 at the completion of exercise, which persisted
      after 30 minutes of recovery (p < 0.05), with no differences evident between the
      groups. Additionally, the perception of recovery after the 30-minute intervention
      was significantly lower in the CON when compared with the CWI and HYP (p < 0.05).
      However, there were no differences in the 12-hour postrecovery time trial
      performances. These results suggest that a 30-minute recovery intervention using
      CWT or HYP has limited influence on the acute-phase response or on improving
      subsequent day athletic performance. However, strength and conditioning
      specialists should encourage the use of a structured postexercise recovery
      procedure because the evidence suggests that the acute perception of recovery is
      much greater when some form of intervention is implemented in comparison with no
      recovery procedure at all.

PMID- 22415457
TI  - Controlled synthesis of olive-shaped Bi2S3/BiVO4 microspheres through a limited
      chemical conversion route and enhanced visible-light-responding photocatalytic
      activity.
AB  - Well-defined olive-shaped Bi(2)S(3)/BiVO(4) microspheres were synthesized through
      a limited chemical conversion route (LCCR), where olive-shaped BiVO(4)
      microspheres and thioacetamide (TAA) were used as precursors and sulfur source,
      respectively. The as-synthesized products were characterized by X-ray diffraction
      (XRD), field emission scanning electron microscopy (FE-SEM), high-resolution
      transmission microscope (HRTEM), X-ray photoelectron spectra (XPS), UV-visible
      diffuse-reflectance spectroscopy (UV-vis DRS), and photoluminescence (PL) spectra
      in detail. Compared with pure BiVO(4) microspheres and Bi(2)S(3) nanorods, the
      Bi(2)S(3)/BiVO(4) products showed obviously enhanced photocatalytic activity for
      the degradation of rhodamine B (Rh B) in aqueous solution under visible-light
      irradiation (lambda > 400 nm). In addition, the Bi(2)S(3)/BiVO(4) composite
      microspheres showed good visible-light-driven photocatalytic activity for the
      degradation of refractory oxytetracycline (OTC) as well. On the basis of UV-vis
      DRS, the calculated energy band positions, and PL spectra, the mechanism of
      enhanced photocatalytic activity of Bi(2)S(3)/BiVO(4) was proposed. The present
      study provides a new strategy to design composite materials with enhanced
      photocatalytic performance.

PMID- 22415456
TI  - Transcriptional variation in the malaria parasite Plasmodium falciparum.
AB  - Malaria genetic variation has been extensively characterized, but the level of
      epigenetic plasticity remains largely unexplored. Here we provide a comprehensive
      characterization of transcriptional variation in the most lethal malaria
      parasite, Plasmodium falciparum, based on highly accurate transcriptional
      analysis of isogenic parasite lines grown under homogeneous conditions. This
      analysis revealed extensive transcriptional heterogeneity within genetically
      homogeneous clonal parasite populations. We show that clonally variant expression
      controlled at the epigenetic level is an intrinsic property of specific genes and
      gene families, the majority of which participate in host-parasite interactions.
      Intrinsic transcriptional variability is not restricted to genes involved in
      immune evasion, but also affects genes linked to lipid metabolism, protein
      folding, erythrocyte remodeling, or transcriptional regulation, among others,
      indicating that epigenetic variation results in both antigenic and functional
      variation. We observed a general association between heterochromatin marks and
      clonally variant expression, extending previous observations for specific genes
      to essentially all variantly expressed gene families. These results suggest that
      phenotypic variation of functionally unrelated P. falciparum gene families is
      mediated by a common mechanism based on reversible formation of H3K9me3-based
      heterochromatin. In changing environments, diversity confers fitness to a
      population. Our results support the idea that P. falciparum uses a bet-hedging
      strategy, as an alternative to directed transcriptional responses, to adapt to
      common fluctuations in its environment. Consistent with this idea, we found that
      transcriptionally different isogenic parasite lines markedly differed in their
      survival to heat-shock mimicking febrile episodes and adapted to periodic heat
      shock with a pattern consistent with natural selection of pre-existing parasites.

PMID- 22415458
TI  - Photipyrones A and B, new pyrone derivatives from the plant endophytic fungus
      Pestalotiopsis photiniae.

PMID- 22415459
TI  - New verticilides, inhibitors of acyl-CoA:cholesterol acyltransferase, produced by
      Verticillium sp. FKI-2679.
AB  - Verticillium sp. FKI-2679, a soil isolate, was found to produce inhibitors of
      acyl-CoA:cholesterol acyltransferase (ACAT) in a cell-based assay using ACAT1-
      and ACAT2-expressing CHO cells. Three new compounds, verticilides A2, A3 and B1,
      were isolated along with a known compound, verticilide A1, from the fermentation
      broth of the fungus by solvent extraction, ODS column chromatography, silica gel
      column chromatography and preparative HPLC. Structure elucidation showed that
      these compounds were new cyclic depsipeptide. Verticilides A1, A2, A3 and B1
      showed a degree of selectivity towards ACAT2, with IC(50)s 8.5-11-fold more
      potent than observed against ACAT1.

PMID- 22415460
TI  - Identification of aluminium dioxalate in fungal cultures grown on vermiculite.

PMID- 22415462
TI  - Spatial heterogeneity in a lyotropic liquid crystal with hexagonal phase.
AB  - Non-ionic surfactant hexaethylene glycol, C(12)E(6), in water self-assembles into
      various kinds of mesophases by varying the surfactant concentration. A spatial
      heterogeneity was discussed on the basis of the diffusion of probe particles
      dispersed in the C(12)E(6)-water solution. Interestingly, at 50 wt% C(12)E(6)
      where the hexagonal structure was formed, two kinds of motion of probe particles
      were observed: some particles normally diffused while others were restricted,
      indicating the existence of a heterogeneity in the physical properties. Such
      heterogeneity can be explained in terms of heterogeneous structures composed of
      hexagonal domains with isotropic-like regions.

PMID- 22415461
TI  - Role of dutasteride in pre-clinical ETS fusion-positive prostate cancer models.
AB  - BACKGROUND: Androgens play a crucial role in prostate cancer, hence the
      androgenic pathway has become an important target of therapeutic intervention.
      Previously we discovered that gene fusions between the 5'-untranslated region of
      androgen regulated gene TMPRSS2 and the ETS transcription factor family members
      were present in a majority of the prostate cancer cases. The resulting aberrant
      overexpression of ETS genes drives tumor progression. METHODS: Here, we evaluated
      the expression levels of 5alpha-reductase isoenzymes in prostate cancer cell
      lines and tissues. We tested the effect of dutasteride, a 5alpha-reductase
      inhibitor, in TMPRSS2-ERG fusion-positive VCaP cell proliferation and cell
      invasion. We also evaluated the effect of dutasteride on the TMPRSS2-ERG fusion
      gene expression. Finally, we tested dutasteride alone or in combination with an
      anti-androgen in VCaP cell xenografts tumor model. RESULTS: Our data showed that
      5alpha-reductase SRD5A1 and SRD5A3 isoenzymes that are responsible for the
      conversion of testosterone to DHT, are highly expressed in metastatic prostate
      cancer compared to benign and localized prostate cancer. Dutasteride treatment
      attenuated VCaP cell proliferation and invasion. VCaP cells pre-treated with
      dutasteride showed a reduction in ERG and PSA expression. In vivo studies
      demonstrated that dutasteride in combination with the anti-androgen bicalutamide
      significantly decreased tumor burden in VCaP cell xenograft model. CONCLUSIONS:
      Our findings suggest that dutasteride can inhibit ERG fusion-positive cell growth
      and in combination with anti-androgen, significantly reduce the tumor burden. Our
      study suggests that anti-androgens used in combination with dutasteride could
      synergistically augment the therapeutic efficacy in the treatment of ETS-positive
      prostate cancer.

PMID- 22415463
TI  - Myocardial perfusion single-photon emission tomography (SPET) and positron
      emission tomography-computed tomography (PET-CT) imaging for congenitally
      corrected transposition of great arteries.
AB  - Congenitally corrected transposition of great arteries (ccTGA) consists of both
      atrioventricular and ventriculo-arterial discordance. In patients with ccTGA, the
      pulmonary artery arises from the left ventricle, whereas the aorta arises from
      the right ventricle. The burden of the systemic blood pressure on the right
      ventricle involves an increased risk of coronary artery disease (CAD) and, as a
      long-term consequence, myocardial hypertrophy and gradual failure. This report
      describes the case of an adult patient affected by ccTGA who was referred for an
      episode of atypical chest pain while at rest. First-line diagnostic examinations
      were inconclusive. Myocardial perfusion single-photon emission tomography (SPET)
      was performed to exclude CAD, but the congenital abnormalities of the patient's
      heart made interpretation of the images particularly difficult. A perfusion
      positron emission tomography-computed tomography (PET-CT) scan with (13)N-ammonia
      then was suggested, which unmasked an unexpected artifact. The case report
      demonstrates that hybrid imaging techniques such as SPET-CT and PET-CT should be
      used systematically when CAD is suspected for patients with abnormal anatomy of
      the heart, including ccTGA.

PMID- 22415465
TI  - Combination radiotherapy in an orthotopic mouse brain tumor model.
AB  - Glioblastoma multiforme (GBM) are the most common and aggressive adult primary
      brain tumors. In recent years there has been substantial progress in the
      understanding of the mechanics of tumor invasion, and direct intracerebral
      inoculation of tumor provides the opportunity of observing the invasive process
      in a physiologically appropriate environment. As far as human brain tumors are
      concerned, the orthotopic models currently available are established either by
      stereotaxic injection of cell suspensions or implantation of a solid piece of
      tumor through a complicated craniotomy procedure. In our technique we harvest
      cells from tissue culture to create a cell suspension used to implant directly
      into the brain. The duration of the surgery is approximately 30 minutes, and as
      the mouse needs to be in a constant surgical plane, an injectable anesthetic is
      used. The mouse is placed in a stereotaxic jig made by Stoetling (figure 1).
      After the surgical area is cleaned and prepared, an incision is made; and the
      bregma is located to determine the location of the craniotomy. The location of
      the craniotomy is 2 mm to the right and 1 mm rostral to the bregma. The depth is
      3 mm from the surface of the skull, and cells are injected at a rate of 2 MUl
      every 2 minutes. The skin is sutured with 5-0 PDS, and the mouse is allowed to
      wake up on a heating pad. From our experience, depending on the cell line,
      treatment can take place from 7-10 days after surgery. Drug delivery is dependent
      on the drug composition. For radiation treatment the mice are anesthetized, and
      put into a custom made jig. Lead covers the mouse's body and exposes only the
      brain of the mouse. The study of tumorigenesis and the evaluation of new
      therapies for GBM require accurate and reproducible brain tumor animal models.
      Thus we use this orthotopic brain model to study the interaction of the
      microenvironment of the brain and the tumor, to test the effectiveness of
      different therapeutic agents with and without radiation.

PMID- 22415466
TI  - Vascular neurobehcet disease: correlation with current disease activity forum and
      systemic vascular involvement.
AB  - Behcet's syndrome (BS) is a chronic relapsing vascular inflammatory disease of
      unknown etiology with high morbidity and mortality. This research aims to study
      the clinical patterns of CNS disease in a group of patients with BS as well as
      the frequency and type of the associated radiographic findings suggestive of
      structural cerebral vascular disease. The findings were studied in relation to
      disease activity and features of systemic vascular involvement. Forty patients
      fulfilling the diagnostic criteria of the International Study Group for Behcet's
      Disease, mean age of 33.56 +/- 9.7 years, were enrolled. Patients were subjected
      to magnetic resonance imaging with conjugate survey of cerebral blood vessels'
      flow pattern abnormalities by transcranial Doppler study. Thirty healthy controls
      were included. Behcet's Disease Current Activity Form Score was used. Neuro
      Behcet's syndrome (NBS) was diagnosed in 37.5% with headache being the most
      common (86.6% of cases), pyramidal affection (signs of upper motor neuron
      lesions/hemiplegia) was reported in 33.3%, attacks of disturbed conscious level
      in 26.6%, and cranial nerve affection in 6.5%. Of the patients, 66.6% with
      clinical features of NBS had statistically significant radiographic evidences of
      cerebrovascular disease (p = 0.01). Patients with NBS had significantly higher
      disease activity index score (r = 0.69, p = 0.0001). Radiographic findings and
      flow abnormalities were significantly less in patients on immune suppressants and
      antiplatelet drugs (p = 0.003, 0.04). BS patients with clinical neurologic
      disease were found to have radiographic findings suggestive of cerebral vascular
      disease with high disease activity index score. Drugs like immunosuppressants and
      oral antiplatelets might retard cerebral vascular disease progression and flow
      abnormalities, respectively.

PMID- 22415467
TI  - Disease activity in systemic lupus erythematosus patients with end-stage renal
      disease: systematic review of the literature.
AB  - It is not unusual that patients with systemic lupus erythematosus (SLE) progress
      to terminal renal failure and subsequently require renal replacement therapy.
      Previous studies have shown that clinical and/or serological remission in
      patients with SLE is common in those who develop end-stage renal disease (ESRD).
      On the other hand, the persistence of lupus activity among patients undergoing
      long-term dialysis is not rare, either. The aim of this study is to define, by
      means of a systematic review, the course of SLE activity in patients who
      developed ESRD. Data were obtained through searches for articles in the MEDLINE
      (1966 to 2011), SCielo, and LILACS databases, using the following keywords:
      "chronic renal failure", "systemic lupus erythematosus", "end-stage renal
      disease", "lupus activity", "disease activity", "lupus flare", "hemodialysis",
      and "renal replacement therapy" and their corresponding translations in
      Portuguese. Twenty-four articles were found which evaluated the degree of lupus
      activity in patients with ESRD. Fifteen of these studies spoke of a substantial
      reduction of clinical and/or serological activity after the development of ESRD,
      while nine articles found that the amount of clinical and/or serological activity
      was similar to that of the phase prior to terminal renal failure, or it occurred
      in at least 50% of the patients studied. Although the majority of studies showed
      that lupus flares tend to decrease in frequency in patients who develop ESRD, in
      this scenario, one should be prepared to correctly diagnose a recurrence of the
      disease, as well as to perform appropriate therapy.

PMID- 22415468
TI  - Dried cytospin preparations of synovial fluid are a stable material for long-time
      storage and delayed crystal analysis.
AB  - The aim of this study was to evaluate dried SF cytospin preparations as a
      suitable medium for long-time storage and delayed crystal analysis. For this
      purpose, we analyzed ten MSU-positive, ten CPPD-positive and 20 crystal-negative
      SF at baseline (wet preparation), after 24 h, 1 week, 4 weeks, 6 months and 12
      months for the occurrence of crystals. After cytocentrifugation for 10 min at 700
      rpm in a Shandon Cytospin 4 cytocentrifuge (Thermo Fisher Scientific, Waltham,
      USA), the sediments were dried on the slides and examined in blinded fashion at
      any time point by an experienced analyst using polarized microscopy. The crystal
      content of the initially MSU- and CPPD-positive samples was positively confirmed
      at any time point of the study, whereas the controls remained crystal-negative
      during the whole study period. Thus, compared to the examined wet preparations at
      baseline, there were no false positive or false negative results observed. In
      conclusion, dried cytospin preparations were confirmed as a suitable material for
      long-time storage and delayed crystal identification.

PMID- 22415470
TI  - Tracking spatial information during reading: a cue-based process.
AB  - The goal of the present set of experiments was to examine whether a cue-based
      mechanism could account for how, and under what conditions, spatial information
      is tracked. In five experiments, reading times were measured for a target
      sentence that contradicted the earlier-described location of a protagonist. When
      the target sentence contained either one or two cues to earlier spatial
      information (Experiments 1a-1c), reading times were disrupted. When all cues were
      eliminated (Experiments 2a and 2b), reading time were disrupted only when readers
      were instructed to take the perspective of the protagonist. The combined results
      of all five experiments are consistent with a cue-based mechanism: Readers encode
      spatial information but do not update earlier-encoded spatial information except
      in response to specific text characteristics (i.e., cues to earlier spatial
      information) or task demands (e.g., an instruction to read from the perspective
      of the protagonist) that increase the accessibility of earlier-encoded spatial
      information.

PMID- 22415469
TI  - Costs and trends in pancreatic cancer treatment.
AB  - BACKGROUND: Pancreatic cancer poses a substantial morbidity and mortality burden
      in the United States, and predominantly affects older adults. The objective of
      this study was to estimate the direct medical costs of pancreatic cancer
      treatment in a population-based cohort of Medicare beneficiaries, and the
      contribution of different treatment modalities and health care services to the
      total cost of care and trends in costs over time. METHODS: In the linked
      Surveillance, Epidemiology, and End Results (SEER)-Medicare database, pancreatic
      cancer patients were identified who were aged 66 years or older and who were
      diagnosed from 2000 to 2007. Total direct medical costs were estimated from
      Medicare payments overall and within categories of care. Costs attributable to
      pancreatic cancer were estimated by subtracting the costs of medical care in a
      matched cohort of cancer-free beneficiaries. RESULTS: A total of 15,037 patients
      were identified, of whom 97% were observed from diagnosis until death. Mean total
      direct medical costs were $65,500. Mean total costs were greater for patients
      with resectable locoregional disease ($134,700) than for those with unresectable
      locoregional or distant disease ($65,300 and $49,000, respectively).
      Hospitalizations and cancer-directed procedures collectively accounted for the
      largest fraction of health care costs. The total cost of care appeared to
      increase slightly over the study period (P = .05). The mean costs attributable to
      pancreatic cancer were $61,700. CONCLUSIONS: Despite poor prognosis and short
      survival, the economic burden of pancreatic cancer in the elderly is substantial.
      Demographic trends, greater use of targeted therapies, and possible
      implementation of screening strategies are likely to impact treatment patterns
      and costs in the future.

PMID- 22415471
TI  - Rare earth hybrid materials of organically modified silica covalently bonded to a
      GaN matrix: multicomponent assembly and multi-color luminescence.
AB  - Three kinds of rare earth hybrid materials with enhanced thermostability and
      photoluminescence properties have been prepared for the first time by using a
      functionalized GaN matrix as one of the building blocks. A number of silane
      coupling agents (isocyanate triethoxysilane (ICTES), 3-chloropropyl
      triethoxysilane (CPTES) and 3-aminopropyl triethoxysilane (APTES)) behave as the
      covalent linkages for modification by both hydroxylation of GaN and
      functionalized photoactive ligands (4-mercaptobenzoic acid (MBA), 4
      hydroxybenzoic acid (HBA) and nitrobenzoyl chloride (NBC)), resulting in the
      precursors (MBA-ICTES-GaN, HBA-CPTES-GaN and NBC-APTES-GaN). Subsequently,
      multicomponent photofunctional rare earth hybrid materials with the three
      precursors and 1,10-phenanthroline (Phen) are assembled and characterized by
      their FTIR spectra, UV-vis diffuse reflectance spectra, XRD patterns, and
      photoluminescent behaviour (luminescence, lifetime, quantum efficiency, and
      energy transfer). These results reveal that the Eu(3+) hybrids with the MBA-ICTES
      GaN unit have a better luminescence intensity ratio, higher quantum efficiency
      and longer lifetime than those with the HBA-CPTES-GaN and NBC-APTES-GaN units.
      Meanwhile the hybrid Phen-Tb-HBA-CPTES-GaN possesses a stronger characteristic
      emission of Tb(3+) ions than the other two hybrids (Phen-Tb-MBA-ICTES-GaN and
      Phen-Tb-NBC-APTES-GaN). Moreover, two-color-based hybrid materials are fabricated
      by combining different molar ratios of Eu(3+) and Tb(3+) in the same system (Phen
      RE-MBA-ICTES-GaN) with emission at a wavelength of 331 nm (RE = Eu, Tb) and
      yellow luminescence can be achieved.

PMID- 22415472
TI  - Should we treat acute HIV infection?
AB  - Critical advances in the early diagnosis of HIV now allow for treatment
      opportunities during acute infection. It remains unclear whether treatment of
      acute HIV infection with antiretroviral therapy improves long-term clinical
      outcomes for the individual and current guidelines are not definitive in
      recommending therapy at this stage of infection. However, treatment of acute HIV
      infection may have short-term benefit on viral set point when compared to delayed
      therapy as well as reducing the risk of transmission to others. Herein we review
      the immunological and clinical literature to discuss whether we should treat
      acute HIV infection, both from the perspective of the individual HIV-infected
      patient and from the public health perspective. As transmission of drug-resistant
      HIV variants are of concern, we also review recent clinical trial data to provide
      recommendations for which specific antiretroviral treatment regimens should be
      considered for the treatment of acute HIV infection.

PMID- 22415473
TI  - HIV-1 prevention for HIV-1 serodiscordant couples.
AB  - A substantial proportion of HIV-1 infected individuals in sub-Saharan Africa are
      in stable relationships with HIV-1 uninfected partners, and HIV-1 serodiscordant
      couples thus represent an important target population for HIV-1 prevention.
      Couple-based HIV-1 testing and counseling facilitates identification of HIV-1
      serodiscordant couples, counseling about risk reduction, and referrals to HIV-1
      treatment, reproductive health services, and support services. Maximizing HIV-1
      prevention for HIV-1 serodiscordant couples requires a combination of strategies,
      including counseling about condoms, sexual risk, fertility, contraception, and
      the clinical and prevention benefits of antiretroviral therapy (ART) for the HIV
      1-infected partner; provision of clinical care and ART for the HIV-1-infected
      partner; antenatal care and services to prevent mother-to-child transmission for
      HIV-1-infected pregnant women; male circumcision for HIV-1-uninfected men; and,
      pending guidelines and demonstration projects, oral pre-exposure prophylaxis
      (PrEP) for HIV-1-uninfected partners.

PMID- 22415474
TI  - Eliminating the HIV reservoir.
AB  - In the past few years, major advances have been achieved in understanding the
      nature and the maintenance mechanisms of the HIV reservoir. Although
      antiretroviral therapy works well in a majority of patients, it faces problems of
      compliance, resistance, toxicity, and cost. In most cases, the remaining HIV
      reservoir precluding antiretroviral cessation consists of a tiny cell pool that
      is long-lived and inaccessible to current therapies. New strategies are therefore
      needed to either purge or control this residual reservoir and finally stop
      antiretroviral drugs. Both ways leading to a functional or a sterilizing cure are
      currently pursued. Several molecules have been identified to achieve these goals
      and some of them have already entered clinical testing in humans. In this
      article, we review recent findings on the biology of HIV persistence and detail
      how HIV eradication trials should be designed in the near future.

PMID- 22415475
TI  - Interpreting indices of physiological stress in free-living vertebrates.
AB  - When vertebrate physiological ecologists use the terms 'stress' or 'physiological
      stress', they typically mean the level of hypothalamus-pituitary-adrenal (HPA-)
      axis activation. Measurements of stress hormone concentrations (e.g.
      glucocorticoids in blood, urine or faeces), leukocytes (e.g. the neutrophil
      lymphocyte ratio or heterophil equivalent), immunofunction (e.g. innate, cell
      mediated or humoral immunity measures) and regenerative anaemia (e.g. mean
      erythrocyte volume and red blood cell distribution width) have all been used to
      estimate HPA-axis activity in free-living vertebrates. Stress metrics have
      provided insights into aspects of autecology or population regulation that could
      not have been easily obtained using other indices of population wellbeing, such
      as body condition or relative abundance. However, short- and long-term stress
      (often problematically termed acute and chronic stress, respectively) can
      interact in unpredictable ways. When animals experience trapping and handling
      stress before blood, faeces and/or urine is sampled, the interaction of short-
      and long-term stress can confound interpretation of the data, a fact not always
      acknowledged in studies of stress in free-living vertebrates. This review
      examines how stress metrics can be confounded when estimates of HPA-axis
      activation are collected for free-living vertebrates and outlines some approaches
      that can be used to help circumvent the influence of potentially confounding
      factors.

PMID- 22415476
TI  - A prospective study of breast lymphedema: frequency, symptoms, and quality of
      life.
AB  - Although lymphedema of the arm is a well-known complication of breast and
      axillary surgery, breast lymphedema has received scant attention. We sought to
      prospectively characterize breast lymphedema's incidence, associated symptoms,
      clinical course, and impact on quality of life. Subjects were enrolled
      prospectively from a consecutive sample of patients undergoing non-mastectomy
      breast procedures (excisional biopsy or wide local excision +/- lymph node
      removal) and followed for signs and symptoms of lymphedema in the operated
      breast. Symptoms and distress were serially assessed with 11-point linear analog
      scales. Breast lymphedema was diagnosed independent of symptoms, based on the
      distribution and degree of edema and erythema. One hundred twenty-four women were
      followed for a median of 11 months, and breast lymphedema was diagnosed in 38
      (31%) women. Breast lymphedema was more frequent after breast surgery with
      axillary node removal (49%) compared to breast surgery alone (0%), p < 0.0001.
      Breast lymphedema involved multiple quadrants in most women and was characterized
      by edema in 100% and erythema in 79%. Patients with breast lymphedema were
      significantly more likely than women without breast lymphedema to report symptoms
      of breast heaviness (65% vs 22%, p < 0.0001), redness (62% vs 29%, p = 0.0006),
      and swelling (59% vs 22%, p < 0.0001), but symptom-associated distress was low
      overall. Three of 32 breast lymphedema patients with clinical follow-up developed
      chronic edema. Breast lymphedema occurs in approximately one-half of women who
      undergo breast surgery with axillary node removal. The condition is characterized
      by diffuse skin edema and erythema as well as self-reported symptoms with a low
      level of distress.

PMID- 22415477
TI  - Second-line bevacizumab-containing therapy in patients with triple-negative
      breast cancer: subgroup analysis of the RIBBON-2 trial.
AB  - Patients with metastatic triple-negative breast cancer (TNBC) typically have a
      poor prognosis and limited treatment options. To determine the impact of
      combining bevacizumab with second-line chemotherapy in patients with metastatic
      TNBC, we performed an exploratory subgroup analysis of the randomized phase 3
      RIBBON-2 trial. RIBBON-2 enrolled patients with metastatic breast cancer that had
      progressed on first-line non-bevacizumab-containing chemotherapy. After selection
      of chemotherapy (taxane, gemcitabine, capecitabine, or vinorelbine), patients
      were randomized 2:1 to receive chemotherapy with either bevacizumab (10 mg/kg
      every 2 weeks or 15 mg/kg every 3 weeks) or placebo. The primary endpoint was
      progression-free survival (PFS). Secondary endpoints included overall survival
      (OS), objective response rate (ORR), and safety. Of 684 patients treated in
      RIBBON-2, 159 (23%) had TNBC. Baseline characteristics were reasonably balanced
      in the two treatment groups. The majority received taxane chemotherapy. The
      hazard ratio (HR) for PFS was 0.494 [95% confidence interval (CI) 0.33-0.74; P =
      0.0006]. Median PFS was 6.0 months with bevacizumab-chemotherapy versus 2.7
      months with chemotherapy alone. Median OS was 17.9 versus 12.6 months,
      respectively (HR 0.624, 95% CI 0.39-1.007; P = 0.0534). ORR was 41 versus 18%,
      respectively (P = 0.0078). The safety profile was consistent with the overall
      study population and previous phase 3 trials of bevacizumab. Patients with
      metastatic TNBC derived significant PFS and response benefits from the
      combination of bevacizumab with second-line chemotherapy. Despite the small
      sample size and immature data, there was a trend toward improved OS.

PMID- 22415478
TI  - The SNP rs895819 in miR-27a is not associated with familial breast cancer risk in
      Italians.

PMID- 22415480
TI  - Atypical ezrin localization as a marker of locally advanced breast cancer.
AB  - Locally advanced breast cancer (LABC) was initially characterized as a large
      primary tumor (>=5 cm), associated with or without skin or chest-wall
      involvement, fixed axillary lymph nodes, or disease spread to the ipsilateral
      internal mammary or supraclavicular nodes. Since 2002, LABC has been reclassified
      to include smaller stage IIB tumors (2 to <5 cm) with lymph node involvement, or
      stages IIIA-IIIB (>=5 cm) with or without nodal involvement. Despite the rather
      common presentation of LABC, it remains a poorly understood and highly variable
      clinical presentation of breast cancer that is a challenge to treatment. Here, we
      characterized a panel of breast tumors of known stage, grade, and key clinical
      pathological parameters for the expression of the protein ezrin, which is
      involved in promoting signaling of the PI3K-Akt-mTOR pathway in response to
      extracellular and tumor micro-environmental signals, and is involved in breast
      cancer invasion and metastasis. We show that ezrin, which resides primarily in
      the apical membrane in normal breast epithelium, relocalizes primarily to the
      cytoplasm in >80 % of traditional (T3) invasive ductal LABC tumors (>=5 cm).
      Cytoplasmic ezrin is very strongly associated with a single characteristic in
      breast cancer-large tumor size. In contrast, in large non-malignant
      fibroadenomas, ezrin staining was similar to that of normal breast epithelium.
      Small (T1, 1 cm) invasive ductal carcinomas displayed largely apical membrane and
      perinuclear ezrin localization with weak cytoplasmic staining. Cytoplasmic ezrin
      localization was also associated with positive lymph node status, but no other
      clinical-pathological features, including hormone receptor status, histological
      or nuclear grade of tumor cell. The cytoplasmic relocalization of ezrin may
      therefore represent a novel marker for large malignant tumor size, reflecting the
      unique biology of LABC.

PMID- 22415479
TI  - 25-Hydroxy vitamin-D, obesity, and associated variables as predictors of breast
      cancer risk and tamoxifen benefit in NSABP-P1.
AB  - Observational studies suggest that host factors are associated with breast cancer
      risk. The influence of obesity, vitamin-D status, insulin resistance,
      inflammation, and elevated adipocytokines in women at high risk of breast cancer
      is unknown. The NSABP-P1 trial population was used for a nested case-control
      study. Cases were drawn from those who developed invasive breast cancer and
      controls selected from unaffected participants (<=4 per case) matched for age,
      race, 5 year Gail score, and geographic location of clinical center as a
      surrogate for latitude. Fasting serum banked at trial enrolment was assayed for
      25-hydroxy vitamin-D (25OHD), insulin, leptin (adipocytokine), and C-reactive
      protein (CRP, marker of inflammation). Logistic regression was used to test for
      associations between study variables and the risk of invasive breast cancer. Two
      hundred and thirty-one cases were matched with 856 controls. Mean age was 54, and
      49% were premenopausal. There were negative correlations for 25OHD with body mass
      index (BMI), insulin, CRP, and leptin. BMI >= 25 kg/m(2) was associated with
      higher breast cancer risk (odds ratio [OR] 1.45, p = 0.02) and tamoxifen
      treatment was associated with lower risk (OR = 0.44, p < 0.001). Suboptimal 25OHD
      (<72 nmol/l) did not influence breast cancer risk (OR = 1.06, p = 0.76). When
      evaluated as continuous variables, 25OHD, insulin, CRP, and leptin levels were
      not associated with breast cancer risk (all p > 0.34). In this high risk
      population, higher BMI was associated with a greater breast cancer risk. Serum
      levels of 25OHD, insulin, CRP, and leptin were not independent predictors of
      either breast cancer risk or tamoxifen benefit.

PMID- 22415482
TI  - The metal selectivity of a short peptide maquette imitating the high-affinity
      metal-binding site of E. coli HypB.
AB  - A seven-residue peptide based on the high-affinity metal-binding site of E. coli
      HypB maintains the nickel-binding activity of the full-length protein. The
      ability of the peptide to bind transition metals other than nickel was explored,
      and is discussed in the context of the function of HypB in hydrogenase
      biosynthesis.

PMID- 22415481
TI  - The role of cytoskeleton, components of inositol phospholipid signaling pathway
      and iron in Ehrlichia canis in vitro proliferation.
AB  - Ehrlichia canis, etiologic agent of Canine Monocytic Ehrlichiosis, is an
      obligatory intracellular bacterium that parasitizes monocytes and macrophages. In
      this study we analyzed the role of the cytoskeleton specifically actin
      microfilaments and microtubules, components of inositol phospholipid signaling
      pathway such as phospholipase C (PLC), protein kinase (PTK) and calcium channels
      as well as the role of iron in the E. canis proliferation in DH82 cells.
      Different inhibitory compounds were used for each component: Cytochalasin D
      (inhibits actin polymerization), Nocodazole (inhibits microtubule
      polymerization), Neomycin (PLC inhibitor), Genistein (PTK inhibitor), Verapamil
      (calcium channel blocker) and Deferoxamine (iron chelator). We observed a
      significant decrease in the total number of bacteria in infected cells treated
      suggesting that these cellular components analized are essentials to E. canis
      proliferation.

PMID- 22415483
TI  - [Surgery in partnership].

PMID- 22415484
TI  - [Clinical trials in surgery. On the way towards evidence-based surgery].
AB  - The Study Centre of the German Surgical Society (SDGC) aims at a sustainable
      support of clinical trials in surgery. The SDGC focuses especially on the
      development and conducting of clinical trials in university and non-academic
      hospitals. This article outlines current fields of action and future perspectives
      of the SDGC.

PMID- 22415485
TI  - [Nursing: partnership with the medical profession on equal terms].
AB  - Partnership on equal terms between the nursing and medical profession at the
      Surgical Department of the University Hospital Heidelberg has become evident as
      shown exemplarily in central patient management, wound management and acute pain
      service. By using the skills of both professions, aims to improve patient care
      and operational procedures have been agreed. The transfer of competencies and
      responsibilities needed to achieve these aims has led to an increase in
      recognition of the nursing profession. Physicians have experienced a clear relief
      in pressure and quality has simultaneously been improved. This partnership leads
      to an atmosphere of respect and recognition.

PMID- 22415486
TI  - [The role of surgery in intensive care medicine].
AB  - The dominant role for the emergence and establishment of intensive care medicine
      can be attributed to surgery. The first critical care units were developed in
      surgical university hospitals. Numerous scientific findings and interventional
      procedures have been contributed to intensive care medicine by surgeons and
      surgical disease symptoms shaped the character of the intensive care units.
      Currently 40% of the intensive care beds in Germany are assigned to surgical
      disciplines and surgery is the prerequisite for this operative intensive care.
      Nevertheless, both the human and ideational impact of surgery on intensive care
      medicine has decreased in recent decades. Through the formation of large
      interdisciplinary intensive care units, surgery continues to be threatened with
      losing its influence even further. Now and in the future, the role of surgery has
      to be the maintenance and enhancement of surgical specialized intensive care
      medicine. Surgery has to make surgical intensive care medicine interesting and
      attractive for physicians again.

PMID- 22415487
TI  - [Surgical standards in perioperative treatment].
AB  - Perioperative medicine includes the areas of clarification, patient safety,
      hygiene standards, prophylaxis for thrombosis and antibiotics, pain therapy and
      morbidity and mortality conference. All these procedures show how complex
      perioperative medicine is.

PMID- 22415488
TI  - [Fast-track: evaluation of a new concept].
AB  - The term fast-track describes the combination of several perioperative evidence
      based measures to form a clinical pathway. The primary aim of fast-track is to
      optimize organ function after surgery in order to avoid general morbidity. At the
      same time patient recovery is dramatically enhanced and discharge from hospital
      is possible much earlier than with traditional perioperative care. This article
      describes the author's experience in implementing a fast-track program for
      elective colonic resection. It shows the current status of scientific evaluation
      of the fast-track concept and discusses typical obstacles during introduction of
      fast-track into the clinical routine in Germany.

PMID- 22415489
TI  - [Surgery and management: natural partners].
AB  - The term management is a description of the functions: planning, organization,
      leadership and control in institutions and the corresponding persons holding
      these powers. In order to efficiently lead a department of surgery, surgeons need
      to possess management qualities and have to be able to act as team leaders. Good
      management of a surgical department leads to avoidance of complications and
      increased profits as well as more efficient use of operating room capacities and
      a better organization within the department.

PMID- 22415490
TI  - [Meaningful advanced training concepts for surgeons].
AB  - A state of the art surgical training is crucial for the attraction of surgery as
      a medical profession. The German surgical community can only succeed in
      overcoming the shortage of young surgeons by the development of an attractive and
      professional training environment. Responsibility for surgical training has to be
      taken by the heads of department as well as by the surgical societies. Good
      surgical training should be deemed to be part of the corporate strategy of German
      hospitals and participation in external courses has to be properly funded by the
      hospital management. On the other hand residents are asked for commitment and
      flexibility and should keep records in logbooks and take part in assessment
      projects to gain continuing feedback on their learning progress. The surgical
      community is in charge of developing a structured but flexible training
      curriculum for each of the eight surgical training trunks. A perfect future
      curriculum has to reflect and cross-link local hospital training programs with a
      central training portfolio of a future Academy of German Surgeons, such as
      workshops, courses and e-learning projects. This challenge has to be dealt with
      in close cooperation by all surgical boards and societies. A common sense of
      surgery as a community in diversity is crucial for the success of this endeavour.

PMID- 22415491
TI  - [Importance of staging laparoscopy for stomach cancer].

PMID- 22415492
TI  - [Calcimimetics: no competition for surgery in primary hyperparathyroidism].

PMID- 22415493
TI  - Sirenomelia sequence with other rare congenital anomalies.

PMID- 22415494
TI  - Addition of cobalamin to iron and folic acid improves hemoglobin rise in
      nutritional anemia.
AB  - OBJECTIVE: To assess whether addition of cobalamin (cbl) to iron-folic acid will
      result in improved response in nutritional anemia. METHODS: This study included
      150 children aged between 0.5-5 y having nutritional anemia. Anemia was
      categorized for severity and red cell morphology. Serum levels of ferritin were
      obtained in all cases while levels of cbl and folic acid (FA) were done only in
      children having macrocytic or dimorphic anemia. Children were randomized to
      receive either iron and FA (Group I) or iron, FA and cbl (Group II). Response to
      treatment was assessed at 2, 4 and 8 wk. RESULTS: Of all the 150 patients, iron
      deficiency was documented in 111 patients. Of the 41 cases in whom, Cbl and FA
      levels were done, 97.56% and 53.66% had deficiency of cbl and FA respectively.
      Patients in group II had higher Hb level at 2, 4 and 8 wk (significant at 4 and 8
      wk). Percentage Hb rise from baseline Hb was significantly higher in group II (p
      0.00). In group II, increase in Hb among cases with macrocytosis and others were
      similar although percentage increase in Hb was more pronounced among patients
      with macrocytic anemia or dimorphic anemia. However, this difference was
      statistically not significant (p = 0.18). CONCLUSIONS: Children receiving cbl in
      addition to iron and FA showed an improved hematological response.

PMID- 22415495
TI  - Enteric Fever presenting as secondary hemophagocytic lymphohistiocytosis.

PMID- 22415496
TI  - Sinus Pericranii: a case report and review of literature.
AB  - Normally, there is no obvious communication between the intracranial and extra
      cranial venous drainages in the head. In Sinus Pericranii, there is an abnormal
      communication, either from the extra cranial system to the intracranial venous
      sinuses or from the intracranial venous system to the extra cranial draining
      veins. Venous anomaly is a collection of non muscular venous blood vessels,
      adhering tightly to the outer surface of the skull and directly communicating
      with an intracranial venous sinus through diploic veins. The varicosities are
      intimately associated with the periostium, are distensible, and vary in size with
      changes in intracranial pressure Sinus pericranii is not a single clinico
      pathologic entity, rather a symptom complex with diverse clinical
      manifestations.In this article,the authors present a case of 8 mo old boy having
      Sinus Pericranii.

PMID- 22415497
TI  - Physicochemical properties determined by DeltapKa for protic ionic liquids based
      on an organic super-strong base with various Bronsted acids.
AB  - Neutralization of an organic super-strong base, 1,8-diazabicyclo-[5,4,0]-undec-7
      ene (DBU), with different Bronsted acids affords a novel series of protic ionic
      liquids (PILs) with wide variations in the DeltapK(a) of the constituent amine
      and acids. The physicochemical properties of these PILs, such as thermal
      properties, density, conductivity, viscosity, self-diffusion coefficient,
      vibrational stretching frequency, and (1)H-chemical shifts of the N-H bond, have
      been studied in detail. The generated PILs have melting temperatures below 100 
      degrees C, and six are liquids at ambient temperatures. Thermogravimetric
      analyses (TGA) conducted under isothermal and programmed heating conditions have
      shown that PILs with DeltapK(a)>= 15 exhibit good thermal stability similar to
      aprotic ionic liquids. For instance, PILs with DeltapK(a) > 20 show remarkably
      high short-term thermal stability up to ca. 450  degrees C under a nitrogen
      atmosphere. The viscosity, ionic conductivity, and molar conductivity of the PILs
      fit well with the Vogel-Fulcher-Tamman equation for their dependencies on
      temperature. The relative cationic and anionic self-diffusion coefficients of the
      PILs estimated by the pulsed-field gradient spin-echo (PGSE) NMR method appear to
      be dependent on the structure and strength of the Bronsted acids. Evaluation of
      the ionicity based on both the Walden plot and PGSE-NMR revealed that it
      increases until DeltapK(a) becomes 15 for the PILs.

PMID- 22415498
TI  - Keeping resolutions.

PMID- 22415499
TI  - Society of trauma nurses.

PMID- 22415500
TI  - Risk factors associated with pressure ulcer development in critically ill
      traumatic spinal cord injury patients.
AB  - Critically ill spinal cord injury (SCI) patients are at high risk for pressure
      ulcers. Research is needed to identify risk factors for pressure ulcers. The aim
      of this study was to investigate risk factors and outcomes of pressure ulcers in
      critically ill SCI patients. This is a retrospective cohort study. Data were
      gathered from medical records of adult patients with SCI admitted to surgical
      intensive care units. Ninety-four SCI patients participated in this study.
      Clinical variables associated with pressure ulcers were as follows: fecal
      management systems, incontinence, acidosis, support surfaces, steroids, and
      additional equipment. Hypotension was the strongest predictor of pressure ulcers.
      Nursing interventions may address risk factors and improve patient outcomes.

PMID- 22415501
TI  - A systematic approach to very important person preparedness for a trauma center.
AB  - Hospitals across the United States are more involved in disaster/rapid response
      planning than ever. This collaboration is often driven by continuing federal and
      state preparedness and all-hazards planning efforts that provide cooperative
      agreement and/or grant support. These efforts currently include programs
      administered by the US assistant secretary for preparedness and response, the US
      Centers for Disease Control and Prevention, the US Department of Defense, and the
      US Department of Homeland Security. Beyond legislated support or mandates, key
      emergency management regulations governing hospital-specific disaster planning
      and response activities are required of hospitals by The Joint Commission, the
      largest national hospital accrediting body. Despite this ongoing, heightened
      awareness and inclusion of health care in local and regional emergency response
      planning, there is 1 partnership to yet strengthen: the relationship between
      community trauma centers and US Secret Service staff responsible for White House
      travel and health care contingency plans. One Michigan hospital system designed a
      program that has made preevent communications and preparedness for rapid very
      important person response with the Secret Service as important as other local all
      hazards planning; the evolution of this partnership is the focus of this article.

PMID- 22415503
TI  - Stopping the ouch of injury: injury prevention for faith community nurses.
AB  - Faith Community Nurses (FCNs) work in congregations to promote health within and
      beyond the faith community. The FCN is in an ideal situation to promote injury
      prevention, but many FCNs lack the resources to facilitate injury-prevention
      programs. Our community teaching hospital's trauma services department undertook
      a project to increase awareness among FCNs of their role in promoting injury
      prevention strategies by developing an injury-prevention resource library and
      hosting a train-the-trainer workshop for FCNs. This endeavor was very successful
      and helped forge an ongoing collaborative relationship between faith communities
      and trauma services.

PMID- 22415504
TI  - Management of incidental findings in the trauma patient: is the trauma team a
      primary care provider as well?
AB  - BACKGROUND: Computed tomographic scanning and tertiary surveys have resulted in
      an increase of incidental findings (IFs) unrelated to the trauma. The goals were
      to (1) characterize the frequency and nature of IFs and (2) explore their
      management by a trauma nurse practitioner. METHODS: A prospective log of IFs and
      follow-up details was maintained by a trauma nurse practitioner. Supplemental
      data were obtained through hospital databases. RESULTS: A total of 404 trauma
      patients were screened for IFs over a 6-month period, and 68% had IFs of varying
      severity. CONCLUSION: IFs are frequent in trauma. Appropriate management and
      follow-up is a major commitment that can be well managed by a trauma nurse
      practitioner.

PMID- 22415505
TI  - Do they really care? How trauma patients perceive nurses' caring behaviors.
AB  - Applying the theory of Nursing as Caring can help the nurse provide care that is
      perceived as caring by moderately to severely injured trauma patients. The Caring
      Behaviors Inventory was administered in a 1-to-1 interview format to hospitalized
      trauma patients in a level 2 trauma center. Nurses were positively perceived in
      their caring behaviors with some variation based on gender and ethnicity. The
      modified Caring Behaviors Inventory is quick to use and is reliable and valid.

PMID- 22415506
TI  - A survey of trauma registrars: job requirements, responsibilities, recruitment,
      and retention.
AB  - Study purpose was to describe trauma registrar job requirements,
      responsibilities, and recruitment/retention practices. An online survey was used.
      One-third required a high school diploma; two-thirds required a college degree.
      Most required skills were medical terminology (66%), database management (65%),
      anatomy (64%), Word (63%). Data responsibilities included abstracting, entry,
      coding, and validating. Few employers required certification. Twenty-six percent
      reported problems with recruitment, and 35% with retention. Salary and lack of
      advancement were primary reasons for employee turnover. Certifications were less
      relevant than skills; the primary focus was data management. Recommendations for
      recruitment/retention include job flexibility, educational opportunities, and
      recognition as a profession.

PMID- 22415508
TI  - Development of a geriatric resuscitation protocol, utilization compliance, and
      outcomes.
AB  - Inconsistent application of trauma service resources and underevaluation of risk
      and resuscitation status in elderly trauma patients are problematic. We describe
      a geriatric protocol that includes initial lactate determination and trauma
      surgery admission. Protocol compliance rates were initial lactate determination,
      67.9%; trauma service admission for overt or compensated (elevated lactate)
      shock, 73.6%; and trauma service consultation for nonshock patients, 67.8%.
      Implementation of this protocol resulted in a trend toward reduced mortality and
      reduced potentially preventable deaths.

PMID- 22415509
TI  - Etiology, diagnosis, and characteristics of facial fracture at a midwestern level
      I trauma center.
AB  - Study purpose was to describe facial fracture frequency, demography, injury
      characteristics, and diagnostic modalities at a Midwestern level I trauma center.
      A retrospective review was conducted on a Midwestern trauma center registry for
      years 2008 and 2009. Patient and injury data were collected along with diagnostic
      modality for facial fracture patients. Comparative statistics were conducted on
      the basis of the number of facial fractures, route of admission, presence of
      traumatic brain injury, and gender. There were 154 patients diagnosed with 443
      facial fractures, representing 5% of the trauma population. Median patient age
      was 45 years. Median number of fractures was 2. Fractures were frequently present
      in orbit (32%), malar bone and maxilla (26%), and the nasal bones (19%). Motor
      vehicle crash was the most common mechanism (47%). Most fractures were diagnosed
      with maxillofacial computed tomography (78%). Males had an odds ratio of 2.5 (95%
      confidence interval, 1.15-5.43) for multiple facial fractures and composed 67% of
      the sample. Traumatic brain injury was diagnosed in 71% of patients. This study
      of a medium-sized city and its surrounding rural areas revealed differences from
      studies in large urban centers. Differences included lower gender ratio, older
      average age, and mechanism of injury. While urban trauma centers report assault
      as a leading cause of facial fracture, this study noted higher frequencies of
      motor vehicle crash and falls and fewer assaults.

PMID- 22415510
TI  - Oral contrast omission in the computed tomographic evaluation of blunt abdominal
      trauma: a literature review.
AB  - The purpose of this review is to examine existing research on oral contrast
      administrating as it pertains to the computed tomographic (CT) evaluation of
      blunt abdominal trauma, as well as to determine the necessity of oral contrast as
      part of a CT scanning universal protocol. Many hospitals routinely administer
      both oral and intravenous contrast prior to abdominal CT scan. There have been
      found to be numerous disadvantages and risks associated with oral contrast
      administration prior to CT scan. There has been a shift in many hospitals over
      the years from traditional CT scanners to multidetector row helical scanners,
      which allow for thinner collimation and higher spatial resolution. With the
      advances in technology, from single detector row to multidetector row helical CT
      scanners, the question whether oral contrast is necessary, useful, or dangerous
      presents itself. There is a significant lack of research on this topic over the
      past 10 years. All of the studies referenced support no longer administering oral
      contrast for the initial evaluation of the patient with blunt abdominal trauma.
      However, the findings of the studies cited in this article are based on small
      sample sizes and low incidences of solid organ, bowel, or mesenteric injuries.
      The current level of available research has significant limitations to support a
      recommendation to eliminate the administration of oral contrast before obtaining
      the initial CT scanning for blunt abdominal trauma. Further research is necessary
      before any conclusion or practice change can be made.

PMID- 22415511
TI  - Durable medical equipment recycling: a pilot program.
AB  - Our unfunded trauma patients often lack the access to adequate health care
      services and equipment after hospital discharge. We have developed and
      implemented a pilot program to provide reclaimed durable medical equipment to
      medically indigent trauma patients. Our program includes the reuse of items such
      as front-wheeled walkers, bedside commodes, shower chairs, crutches, and canes.

PMID- 22415512
TI  - Multiple domains in MtENOD8 protein including the signal peptide target it to the
      symbiosome.
AB  - Symbiotic nitrogen fixation occurs in nodules, specialized organs on the roots of
      legumes. Within nodules, host plant cells are infected with rhizobia that are
      encapsulated by a plant-derived membrane forming a novel organelle, the
      symbiosome. In Medicago truncatula, the symbiosome consists of the symbiosome
      membrane, a single rhizobium, and the soluble space between them, called the
      symbiosome space. The symbiosome space is enriched with plant-derived proteins,
      including the M. truncatula EARLY NODULIN8 (MtENOD8) protein. Here, we present
      evidence from green fluorescent protein (GFP) fusion experiments that the MtENOD8
      protein contains at least three symbiosome targeting domains, including its N
      terminal signal peptide (SP). When ectopically expressed in nonnodulated root
      tissue, the MtENOD8 SP delivers GFP to the vacuole. During the course of
      nodulation, there is a nodule-specific redirection of MtENOD8-SP-GFP from the
      vacuole to punctate intermediates and subsequently to symbiosomes, with
      redirection of MtENOD8-SP-GFP from the vacuole to punctate intermediates
      preceding intracellular rhizobial infection. Experiments with M. truncatula
      mutants having defects in rhizobial infection and symbiosome development
      demonstrated that the MtNIP/LATD gene is required for redirection of the MtENOD8
      SP-GFP from the vacuoles to punctate intermediates in nodules. Our evidence shows
      that MtENOD8 has evolved redundant targeting sequences for symbiosome targeting
      and that intracellular localization of ectopically expressed MtENOD8-SP-GFP is
      useful as a marker for monitoring the extent of development in mutant nodules.

PMID- 22415513
TI  - Barley ROP binding kinase1 is involved in microtubule organization and in basal
      penetration resistance to the barley powdery mildew fungus.
AB  - Certain plant receptor-like cytoplasmic kinases were reported to interact with
      small monomeric G-proteins of the RHO of plant (ROP; also called RAC) family in
      planta and to be activated by this interaction in vitro. We identified a barley
      (Hordeum vulgare) partial cDNA of a ROP binding protein kinase (HvRBK1) in yeast
      (Saccharomyces cerevisiae) two-hybrid screenings with barley HvROP bait proteins.
      Protein interaction of the constitutively activated (CA) barley HvROPs CA HvRACB
      and CA HvRAC1 with full-length HvRBK1 was verified in yeast and in planta. Green
      fluorescent protein-tagged HvRBK1 appears in the cytoplasm and nucleoplasm, but
      CA HvRACB or CA HvRAC1 can recruit green fluorescent protein-HvRBK1 to the cell
      periphery. Barley HvRBK1 is an active kinase in vitro, and activity is enhanced
      by CA HvRACB or GTP-loaded HvRAC1. Hence, HvRBK1 might act downstream of active
      HvROPs. Transient-induced gene silencing of barley HvRBK1 supported penetration
      by the parasitic fungus Blumeria graminis f. sp. hordei, suggesting a function of
      the protein in basal disease resistance. Transient knockdown of HvRBK1 also
      influenced the stability of cortical microtubules in barley epidermal cells.
      Hence, HvRBK1 might function in basal resistance to powdery mildew by influencing
      microtubule organization.

PMID- 22415516
TI  - Silicon-containing polymer-derived ceramic nanocomposites (PDC-NCs): preparative
      approaches and properties.
AB  - Composites consist by definition of at least two materials (Gibbsian phases) with
      rather different properties. They exhibit a heterogeneous microstructure and
      possess improved properties with respect to their components. Furthermore, the
      design of their microstructure allows for tailoring their overall properties. In
      the last decades, intense work was performed on the synthesis of nanocomposites,
      which have the feature that at least one of their components is nanoscaled.
      However, the microstructure-property relationship of nanocomposite materials is
      still a challenging topic. This tutorial review paper deals with a special class
      of nanocomposites, i.e. polymer-derived ceramic nanocomposites (PDC-NCs), which
      have been shown to be promising materials for various structural and functional
      applications. Within this context, different preparative approaches for PDC-NCs
      as well as some of their properties will be presented and discussed. Furthermore,
      recent results concerning the relationship between the nano/microstructure of PDC
      NCs and their properties will be highlighted.

PMID- 22415514
TI  - Reactive oxygen species-driven transcription in Arabidopsis under oxygen
      deprivation.
AB  - Reactive oxygen species (ROS) play an important role as triggers of gene
      expression during biotic and abiotic stresses, among which is low oxygen (O(2)).
      Previous studies have shown that ROS regulation under low O(2) is driven by a RHO
      like GTPase that allows tight control of hydrogen peroxide (H(2)O(2)) production.
      H(2)O(2) is thought to regulate the expression of heat shock proteins, in a
      mechanism that is common to both O(2) deprivation and to heat stress. In this
      work, we used publicly available Arabidopsis (Arabidopsis thaliana) microarray
      datasets related to ROS and O(2) deprivation to define transcriptome convergence
      pattern. Our results show that although Arabidopsis response to anoxic and
      hypoxic treatments share a common core of genes related to the anaerobic
      metabolism, they differ in terms of ROS-related gene response. We propose that
      H(2)O(2) production under O(2) deprivation is a trait present in a very early
      phase of anoxia, and that ROS are needed for the regulation of a set of genes
      belonging to the heat shock protein and ROS-mediated groups. This mechanism,
      likely not regulated via the N-end rule pathway for O(2) sensing, is probably
      mediated by a NADPH oxidase and it is involved in plant tolerance to the stress.

PMID- 22415515
TI  - RecA-dependent DNA repair results in increased heteroplasmy of the Arabidopsis
      mitochondrial genome.
AB  - Plant mitochondria have very active DNA recombination activities that are
      responsible for its plastic structures and that should be involved in the repair
      of double-strand breaks in the mitochondrial genome. Little is still known on
      plant mitochondrial DNA repair, but repair by recombination is believed to be a
      major determinant in the rapid evolution of plant mitochondrial genomes. In
      flowering plants, mitochondria possess at least two eubacteria-type RecA proteins
      that should be core components of the mitochondrial repair mechanisms. We have
      performed functional analyses of the two Arabidopsis (Arabidopsis thaliana)
      mitochondrial RecAs (RECA2 and RECA3) to assess their potential roles in
      recombination-dependent repair. Heterologous expression in Escherichia coli
      revealed that RECA2 and RECA3 have overlapping as well as specific activities
      that allow them to partially complement bacterial repair pathways. RECA2 and
      RECA3 have similar patterns of expression, and mutants of either display the same
      molecular phenotypes of increased recombination between intermediate-size
      repeats, thus suggesting that they act in the same recombination pathways.
      However, RECA2 is essential past the seedling stage and should have additional
      important functions. Treatment of plants with several DNA-damaging drugs further
      showed that RECA3 is required for different recombination-dependent repair
      pathways that significantly contribute to plant fitness under stress. Replication
      repair of double-strand breaks results in the accumulation of crossovers that
      increase the heteroplasmic state of the mitochondrial DNA. It was shown that
      these are transmitted to the plant progeny, enhancing the potential for
      mitochondrial genome evolution.

PMID- 22415519
TI  - Epigenetic down regulation of RASSF10 and its possible clinical implication in
      prostate carcinoma.
AB  - BACKGROUND: Ras association domain family (RASSF) comprises several tumor
      suppressor genes, which are often epigenetically inactivated in human tumors.
      Here, we aim to analyze the relevance of the recently identified member RASSF10
      in prostate carcinogenesis. METHODS: RASSF10 promoter methylation and mRNA
      expression were investigated by bisulfite-pyrosequencing and qRT-PCR,
      respectively, in prostate carcinoma (PCa) cell lines (LNCaP, 22Rv1, DU-145) and
      in 83 primary PCa and 53 primary benign prostatic hyperplasia (BPH) tissues
      obtained after radical prostatectomy. Histological localization of RASSF10 was
      done by in situ hybridization. To prove the epigenetic nature of RASSF10 down
      regulation, PCa cell lines were treated with 5-aza-2-deoxycytidine and
      trichostatin A. Potential function of RASSF10 was analyzed in LNCaP by colony
      formation and apoptosis assays. RESULTS: RASSF10 mRNA was localized to cells of
      the basal layer of the prostatic gland. Absence (LNCaP) and decrease (22Rv1, DU
      145) of RASSF10 expression was associated with promoter methylation and could be
      restored by demethylating agents. A link between RASSF10 mRNA reduction and
      promoter methylation was also detected in primary prostate tissues (P = 0.006),
      where PCa showed more frequently reduced RASSF10 levels when compared with BPH
      (33.7% vs. 13.2%, P = 0.009). RASSF10 methylation could be further associated
      with advanced tumor stage and advanced age (P-values < 0.05). Our preliminary
      functional assays revealed the ability of RASSF10 to inhibit colony formation (P
      = 0.018) and to increase apoptosis (P = 0.035). CONCLUSIONS: This is the first
      study, which demonstrates the frequent epigenetic inactivation of RASSF10 in PCa
      and its implication in clinical symptoms of PCa.

PMID- 22415520
TI  - Genetic variants of organic cation transporter 1 (OCT1) and OCT2 significantly
      reduce lamivudine uptake.
AB  - The study sought to investigate the effect of genetic variants of OCT1 (OCT1
      P283L and -P341L) and OCT2 (OCT2-T199I, -T201M and -A270S), which were identified
      in a Korean population, on the transport of lamivudine in vitro and to compare
      the substrate dependent effects of OCT1 and OCT2 variants with 1-methyl-4
      phenylpyridinium (MPP+), tetraethyl ammonium (TEA), metformin and lamivudine as
      substrates for these transporters. When the transport kinetics of lamivudine
      uptake in oocytes overexpressing OCT1 and OCT2 wild-type (WT) and variant
      proteins were measured, lamivudine uptake mediated by OCT1-WT was saturable, and
      uptake was decreased in oocytes expressing OCT1-P283L and -P341L variants
      compared with that in OCT1-WT. The Clint of lamivudine in oocytes expressing OCT1
      P283L was decreased by 85.1% compared with OCT1-WT, whereas it was decreased by
      48.7% in oocytes expressing OCT1-P341L. The Clint of lamivudine in oocytes
      expressing OCT2-T199I, -T201M and -A270S was decreased by 86.2%, 88.9% and 73.6%,
      respectively, compared with OCT2-WT. When comparing various substrates such as
      MPP+, TEA, metformin and lamivudine, the effects of the OCT1 genetic
      polymorphisms on their uptake were not identical. However, contrary to the case
      of OCT1, the uptake of MPP+, TEA, metformin and lamivudine in oocytes expressing
      OCT2-T199I, -T201M and -A270S variants was decreased significantly compared with
      that in oocytes expressing OCT2-WT. In conclusion, the effect of genetic
      variations of OCT1 and OCT2 on the uptake of MPP+, TEA, metformin and lamivudine
      was substrate-dependent.

PMID- 22415521
TI  - Growth assays to assess polyglutamine toxicity in yeast.
AB  - Protein misfolding is associated with many human diseases, particularly
      neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and
      Huntington's disease. Huntington's disease (HD) is caused by the abnormal
      expansion of a polyglutamine (polyQ) region within the protein huntingtin. The
      polyQ-expanded huntingtin protein attains an aberrant conformation (i.e. it
      misfolds) and causes cellular toxicity. At least eight further neurodegenerative
      diseases are caused by polyQ-expansions, including the Spinocerebellar Ataxias
      and Kennedy's disease. The model organism yeast has facilitated significant
      insights into the cellular and molecular basis of polyQ-toxicity, including the
      impact of intra- and inter-molecular factors of polyQ-toxicity, and the
      identification of cellular pathways that are impaired in cells expressing polyQ
      expansion proteins. Importantly, many aspects of polyQ-toxicity that were found
      in yeast were reproduced in other experimental systems and to some extent in
      samples from HD patients, thus demonstrating the significance of the yeast model
      for the discovery of basic mechanisms underpinning polyQ-toxicity. A direct and
      relatively simple way to determine polyQ-toxicity in yeast is to measure growth
      defects of yeast cells expressing polyQ-expansion proteins. This manuscript
      describes three complementary experimental approaches to determine polyQ-toxicity
      in yeast by measuring the growth of yeast cells expressing polyQ-expansion
      proteins. The first two experimental approaches monitor yeast growth on plates,
      the third approach monitors the growth of liquid yeast cultures using the
      BioscreenC instrument. Furthermore, this manuscript describes experimental
      difficulties that can occur when handling yeast polyQ models and outlines
      strategies that will help to avoid or minimize these difficulties. The protocols
      described here can be used to identify and to characterize genetic pathways and
      small molecules that modulate polyQ-toxicity. Moreover, the described assays may
      serve as templates for accurate analyses of the toxicity caused by other disease
      associated misfolded proteins in yeast models.

PMID- 22415522
TI  - Functional roles and foundational characteristics of psychologists in integrated
      primary care.
AB  - Psychologists are presented with unprecedented opportunities to integrate their
      work in primary care settings. Although some roles of psychologists in primary
      care overlap with those in traditional psychology practice settings, a number are
      distinct reflecting the uniqueness of the primary care culture. In this paper, we
      first describe the integrated primary care setting, with a focus on those
      settings that have components of patient centered medical home. We then describe
      functional roles and foundational characteristics of psychologists in integrated
      primary care. The description of functional roles emphasizes the diversity of
      roles performed. The foundational characteristics identified are those that we
      consider the 'primary care ethic,' or core characteristics of psychologists that
      serve as the basis for the various functional roles in integrated primary care.
      The 'primary care ethic' includes attitudes, values, knowledge, and abilities
      that are essential to the psychologist being a valued, effective, and productive
      primary care team member.

PMID- 22415523
TI  - Cognitive, health, and sociodemographic predictors of longitudinal decline in
      hearing acuity among older adults.
AB  - BACKGROUND: We aimed to investigate predictors of change in pure-tone hearing
      thresholds in older adults. METHODS: Data were drawn from a pooled sample from
      the Dynamic Analyses to Optimise Ageing (DYNOPTA) project (N = 4,221, mean age =
      73.6, range: 50-103 years). Pure-tone hearing thresholds were tested for
      frequencies between 0.5 and 8 kHz, on up to four occasions over a period of 11
      years. Linear mixed models tested for predictors of change in hearing. RESULTS:
      Hearing loss for high-range frequencies preceded decline in low-range
      frequencies. Men had higher baseline hearing thresholds, but women experienced
      faster rates of decline in hearing for mid- to high-range frequencies. The
      estimated rate of change for a 75-year-old adult was 0.91 decibel hearing level
      (dB HL) per year for pure-tone thresholds averaged over frequencies ranging
      between 0.5 and 4 kHz in the better ear. Baseline age (beta = 0.03, p < .01),
      hypertension (beta = 0.15, p < .01), and probable cognitive impairment (beta =
      0.40, p = .01) were independent predictors of annual rate of change in hearing
      thresholds. Incidence of probable cognitive impairment was also associated with
      higher hearing thresholds. Other known correlates for prevalence of hearing
      impairment, including low education, noise damage, diabetes, and history of
      stroke were independently associated with baseline levels of hearing but were not
      predictive of change in hearing thresholds. CONCLUSIONS: Faster rates of decline
      in hearing are predicted by probable cognitive impairment and hypertension.

PMID- 22415524
TI  - Are multiple visual short-term memory storages necessary to explain the retro-cue
      effect?
AB  - Recent research has shown that change detection performance is enhanced when,
      during the retention interval, attention is cued to the location of the upcoming
      test item. This retro-cue advantage has led some researchers to suggest that
      visual short-term memory (VSTM) is divided into a durable, limited-capacity
      storage and a more fragile, high-capacity storage. Consequently, performance is
      poor on the no-cue trials because fragile VSTM is overwritten by the test display
      and only durable VSTM is accessible under these conditions. In contrast,
      performance is improved in the retro-cue condition because attention keeps
      fragile VSTM accessible. The aim of the present study was to test the assumptions
      underlying this two-storage account. Participants were asked to encode an array
      of colors for a change detection task involving no-cue and retro-cue trials. A
      retro-cue advantage was found even when the cue was presented after a visual
      (Experiment 1) or a central (Experiment 2) interference. Furthermore, the
      magnitude of the interference was comparable between the no-cue and retro-cue
      trials. These data undermine the main empirical support for the two-storage
      account and suggest that the presence of a retro-cue benefit cannot be used to
      differentiate between different VSTM storages.

PMID- 22415525
TI  - Hypoxia-inducible factor prolyl hydroxylase inhibition: robust new target or
      another big bust for stroke therapeutics?
AB  - A major challenge in developing stroke therapeutics that augment adaptive
      pathways to stress has been to identify targets that can activate compensatory
      programs without inducing or adding to the stress of injury. In this regard,
      hypoxia-inducible factor prolyl hydroxylases (HIF PHDs) are central gatekeepers
      of posttranscriptional and transcriptional adaptation to hypoxia, oxidative
      stress, and excitotoxicity. Indeed, some of the known salutary effects of
      putative 'antioxidant' iron chelators in ischemic and hemorrhagic stroke may
      derive from their abilities to inhibit this family of iron, 2-oxoglutarate, and
      oxygen-dependent enzymes. Evidence from a number of laboratories supports the
      notion that HIF PHD inhibition can improve histological and functional outcomes
      in ischemic and hemorrhagic stroke models. In this review, we discuss this
      evidence and highlight important gaps in our understanding that render HIF PHD
      inhibition a promising but not yet preclinically validated target for protection
      and repair after stroke.

PMID- 22415527
TI  - Optimizing size thresholds in a plant-pollinator interaction web: towards a
      mechanistic understanding of ecological networks.
AB  - Using functional traits together with abundance effects strengthens the
      prediction of interactions between pairs of species in ecological networks.
      Insights into the way species interact as well as prediction accuracy can be
      gained when thresholds for trait value combinations that make interactions
      possible are optimized through model selection. I present novel data of two
      subalpine plant-pollinator communities and build several stochastic models
      integrating flower abundance and morphological threshold rules that allow or
      restrict interactions between species. The number of correctly predicted
      interactions was highest when thresholds were set so that the insect's proboscis
      was not shorter than the nectar-holder depth minus 1-1.6 mm, and not wider than
      the nectar-holder width minus 0.5 mm. In comparison with models based solely on
      plant abundance effects, the model incorporating optimized size thresholds better
      predicted the distribution of the trait differences between plants and insects.
      This indicates that a mechanistic approach of interaction webs based on optimized
      size thresholds provides valuable information on community structure. The
      possible implications for community functioning are discussed.

PMID- 22415529
TI  - Copper(I) coordination polymers of 2,2'-dipyridylamine derivatives: syntheses,
      structures, and luminescence.
AB  - Reactions of CuX (X = Br(-), I(-) or CN(-)) with various types of 2,2'
      dipyridylamine (dpa) derivatives have been performed via a hydrothermal
      solvothermal method and the products have been structurally characterized by X
      ray crystallography. Four ligands with different coordination motifs were
      employed in the reactions, including angular N,N,N',N'-tetra(2-pyridyl)-2,6
      pyridinediamine (tppda); linear N,N,N',N'-tetra(2-pyridyl)-1,4-phenylenediamine
      (tppa) and N,N,N',N'-tetra(2-pyridyl)biphenyl-4,4'-diamine (tpbpa); and star
      shaped tris-[4-(2,2'-dipyridylamino)-phenyl]amine (tdpa), which yielded eight
      copper(I) complexes exhibiting different stoichiometries of Cu-dpa and variable
      coordination modes of dpa. The compound [Cu(2)(tppda)(MU-I)(2)](n) (1) forms a
      one dimensional (1D) coordination polymer exclusively through double MU(2)-I
      bridges, which arranges to two dimensional (2D) metal-organic frameworks (MOFs)
      via the face-to-face pi...pi stacking interactions from pyridyl rings. The
      compound [Cu(6)(tppa)(MU(3)-Br)(6)](n) (2) forms a 2D network linked through
      multiple MU(3)-Br bridges. The compound [Cu(2)(tppa)(MU-CN)(2)](n) (3) is also a
      2D MOF containing 1D (CuCN)(n) chains. The compounds [Cu(tpbpa)Br](n) (4) and
      [Cu(4)(tpbpa)(2)(MU-I)(4)](n) (5) display two different 1D assemblies: a zig-zag
      chain for 4 and a linear structure for 5. The compound [Cu(4)(tpbpa)(MU
      CN)(4)](n) (6) shows a pseudo-4,8(2) topological net, while the compound
      [Cu(8)(tpbpa)(MU-CN)(8)](n).2nH(2)O (7) exhibits a three-dimensional (3D)
      framework containing a ...PM... double helical structure, although both of them
      contain (CuCN)(n) chains. The compound [Cu(2)(tdpa)(MU-I)(2)](n) (8) is a zig-zag
      chain based on the star-shaped molecule tpda, in which one of three dpa-arms is
      free of coordination to metal ions. All complexes exhibit luminescence in the
      solid state.

PMID- 22415526
TI  - The impact of portal vein resection on outcomes for hilar cholangiocarcinoma: a
      multi-institutional analysis of 305 cases.
AB  - BACKGROUND. Surgical strategy for hilar cholangiocarcinoma often includes
      hepatectomy, but the role of portal vein resection (PVR) remains controversial.
      In this study, the authors sought to identify factors associated with outcome
      after surgical management of hilar cholangiocarcinoma and examined the impact of
      PVR on survival. METHODS: Three hundred five patients who underwent curative
      intent surgery for hilar cholangiocarcinoma between 1984 and 2010 were identified
      from an international, multi-institutional database. Clinicopathologic data were
      evaluated using univariate and multivariate analyses. RESULTS: Most patients had
      hilar cholangiocarcinoma with tumors classified as T3/T4 (51.1%) and Bismuth
      Corlette type II/III (60.9%). Resection involved extrahepatic bile duct resection
      (EHBR) alone (26.6%); or hepatectomy and EHBR without PVR (56.7%); or combined
      hepatectomy, EHBR, and PVR (16.7%). Negative resection (R0) margin status was
      higher among the patients who underwent hepatectomy plus EHBR (without PVR,
      64.2%; with PVR, 66.7%) versus EHBR alone (54.3%; P < .001). The median number of
      lymph nodes assessed was higher among the patients who underwent hepatectomy plus
      EHBR (without PVR, 6 lymph nodes; with PVR, 4 lymph nodes) versus EHBR alone (2
      lymph nodes; P < .001). The 90-day mortality rate was lower for patients who
      underwent EHBR alone (1.2%) compared with the rate for patients who underwent
      hepatectomy plus EHBR (without PVR, 10.6%, with PVR, 17.6%; P < .001). The
      overall 5-year survival rate was 20.2%. Factors that were associated with an
      adverse prognosis included lymph node metastasis (hazard ratio [HR], 1.79; P =
      .002) and R1 margin status (HR, 1.81; P < .001). Microscopic vascular invasion
      did not influence survival (HR, 1.23; P = .19). Among the patients who underwent
      hepatectomy plus EHBR, PVR was not associated with a worse long-term outcome (P =
      .76). CONCLUSIONS: EHBR alone was associated with a greater risk of positive
      surgical margins and worse lymph node clearance. The current results indicated
      that hepatectomy should be considered the standard treatment for hilar
      cholangiocarcinoma, and PVR should be undertaken when necessary to extirpate all
      disease. Combined hepatectomy, EHBR, and PVR can offer long-term survival in some
      patients with advanced hilar cholangiocarcinoma.

PMID- 22415530
TI  - A survey of anesthesiologists' views of operating room recycling.
AB  - BACKGROUND: Operating rooms contribute significantly to the increasing volumes
      and costs of hospital waste. Little is known, however, about doctors' views of
      hospital waste recycling despite their potential influence in improving recycling
      programs. We surveyed the waste recycling views held by anesthesiologists in
      Australia, New Zealand, and England in regional or metropolitan and public or
      private practice. We asked the following: (1) What proportion of
      anesthesiologists consider recycling operating room waste to be important? (2)
      What do respondents consider to be identifiable barriers preventing operating
      room recycling? METHODS: We performed a Web-based survey of 11 questions of
      attitudes to operating room waste recycling held by anesthesiologists. After
      piloting, the survey was e-mailed to 500 randomly selected Fellows of the
      Australian and New Zealand College of Anesthetists. All anesthetic departments of
      the National Health Service of England also received the e-mail with a request
      that English consultant anesthesiologists complete the survey. RESULTS: We
      received 780 responses from anesthesiologists, 210 (41% response rate) from
      Australia and New Zealand and 570 (11% response rate at worst) from England.
      Regardless of location or type of practice, most (725, 93%; 95% confidence
      interval [CI]: 91% to 95%) responding anesthesiologists would like to increase
      recycling of operating room waste and would commit their time, but not their
      money to doing so. Only 87 (11%; 95% CI: 9% to 14%) respondents agreed/strongly
      agreed that waste recycling occurred in their operating rooms already. Survey
      respondents thought that the greatest barriers to recycling waste were (1)
      inadequate recycling facilities, 381 (49%); (2) negative staff attitudes, 133
      (17%); and (3) inadequate information on how to recycle waste, 121 (16%). Time,
      safety, inadequate space for recycling receptacles, and cost were each thought by
      <5% of respondents to be the greatest barrier to recycling. CONCLUSIONS: Most
      responding anesthesiologists supported greater operating room waste recycling but
      thought that there were identifiable barriers. Anesthesiologists could take a
      leadership role and work with other hospital employees to improve operating room
      recycling. We suggest studies of the effect of improving operating room recycling
      facilities, education, and staff attitudes.

PMID- 22415531
TI  - Case report: anterior mediastinal central line malposition.
AB  - Central venous catheter (CVC) placement is a routine procedure in the management
      of critically ill patients. It is important to ensure correct positioning of the
      catheter tip just above the junction of the superior vena cava and the right
      atrium, to reduce associated complications and to optimize catheter function. The
      incidence of catheter misplacement is approximately 3%-4% for both subclavian and
      internal jugular vein access procedures. CVC placement in the right subclavian
      vein is associated with a higher risk of malposition.(1) We report an unexpected
      secondary malposition of a right subclavian CVC in the anterior mediastinum, with
      resultant vena caval perforation in a patient admitted to the neuro-critical care
      unit after undergoing a craniotomy procedure. 

PMID- 22415532
TI  - Novel double and single ryanodine receptor 1 variants in two Austrian malignant
      hyperthermia families.
AB  - BACKGROUND: Malignant hyperthermia (MH) is a potentially lethal genetic disorder
      in response to volatile anesthetics and depolarizing muscle relaxants. To support
      the claim that a novel genetic variant causes MH, it is necessary to demonstrate
      that it has significant effects on the sensitivity of the ryanodine receptor
      (RYR1) calcium channel. In this study we focused on 2 Austrian families with
      strong MH disposition and new RYR1 variants. METHODS: We sequenced the entire
      coding region of the RYR1 from 2 Austrian MH individuals. Genotype-phenotype
      segregation and evolutionary conservation of the variants were considered. On a
      functional level, Ca(2+) release experiments with fura-2-acetoxymethyl ester were
      performed in cultured skeletal muscle cells derived from individuals carrying the
      new variants and compared with control cells from nonsusceptible individuals.
      Caffeine, 4-chloro-m-cresole (4-CmC), and halothane were used as specific Ca(2+)
      releasing agents. RESULTS: The variant p.A612P in family A segregated with an MH
      susceptible phenotype and cells showed an increased sensitivity for all Ca(2+)
      releasing substances tested. In family B, 2 variants (p.R2458H/p.R3348C) were
      identified. While p.R2458H and p.R2458H/p.R3348C segregated with an MH
      susceptible diagnosis, p.R3348C alone showed an MH equivocal diagnosis. Ca(2+)
      release experiments showed that exchanges of these highly conserved amino acids
      increased the sensitivities for the substances tested (except 4-CmC with p.R2458H
      and p.R3348C) when compared with the MH-negative control group. CONCLUSIONS: Our
      results suggest that these variants are new causative MH variants.

PMID- 22415533
TI  - Managing fresh gas flow to reduce environmental contamination.
AB  - Anesthetic drugs have the potential to contribute to global warming. There is
      some debate about the overall impact of anesthetic drugs relative to carbon
      dioxide, but there is no question that practice patterns can limit the degree of
      environmental contamination. In particular, careful attention to managing fresh
      gas flow can use anesthetic drugs more efficiently--reducing waste while
      achieving the same effect on the patient. The environmental impact of a single
      case may be minimal, but when compounded over an entire career, the manner in
      which fresh gas flow is managed by each individual practitioner can make a
      significant difference in the volume of anesthetic gases released into the
      atmosphere. The maintenance phase of anesthesia is the best opportunity to reduce
      fresh gas flow because circuit gas concentrations are relatively stable and it is
      often the longest phase of the procedure. There are, however, methods for
      managing fresh gas flow during induction and emergence that can reduce the amount
      of wasted anesthetic vapor. This article provides background information and
      discusses strategies for managing fresh gas flow during each phase of anesthesia
      with the goal of reducing waste when using a circle anesthesia system. Monitoring
      oxygen and anesthetic gas concentrations is essential to implementing these
      strategies safely and effectively. Future technological advances in anesthetic
      delivery systems are needed to make it less challenging to manage fresh gas flow.

PMID- 22415534
TI  - The efficacy of morphine, pregabalin, gabapentin, and duloxetine on mechanical
      allodynia is different from that on neuroma pain in the rat neuropathic pain
      model.
AB  - BACKGROUND: It has been reported that <50% of neuropathic pain patients are
      satisfactorily treated with drugs. It is possible that this lack of efficacy of
      drugs on neuropathic pain might be due to the drugs prescribed, regardless of the
      origin of pain. We compared the efficacy of orally administered morphine,
      pregabalin, gabapentin, and duloxetine on mechanical allodynia with that on
      neuroma pain using the tibial neuroma transposition (TNT) model. METHODS: In the
      TNT model, the tibial nerve is transected, and the tibial nerve stump is
      transpositioned to the lateral aspect of the hindlimb. After TNT injury,
      mechanical allodynia and neuroma pain are observed. Morphine, pregabalin,
      gabapentin, and duloxetine were administered orally and were examined for the
      antiallodynic and antineuroma pain effects. RESULTS: Morphine, pregabalin,
      gabapentin, and duloxetine attenuated the level of mechanical allodynia in a dose
      dependent manner. Morphine-but not pregabalin, gabapentin, and duloxetine
      attenuated the neuroma pain. Morphine was less potent in neuroma pain than in
      mechanical allodynia. In the 2-drug-combination studies (morphine + pregabalin,
      morphine + duloxetine, and pregabalin + duloxetine), all drug combinations
      produced a synergistic effect on mechanical allodynia, but not on neuroma pain.
      CONCLUSIONS: These data indicate that the potency of morphine and the efficacy of
      pregabalin, gabapentin, and duloxetine on mechanical allodynia are different from
      those on neuroma pain and that combination therapy is one of different
      therapeutic choices for the treatment of neuropathic pain.

PMID- 22415535
TI  - The prevention of chronic postsurgical pain using gabapentin and pregabalin: a
      combined systematic review and meta-analysis.
AB  - BACKGROUND: Many clinical trials have demonstrated the effectiveness of
      gabapentin and pregabalin administration in the perioperative period as an
      adjunct to reduce acute postoperative pain. However, very few clinical trials
      have examined the use of gabapentin and pregabalin for the prevention of chronic
      postsurgical pain (CPSP). We (1) systematically reviewed the published literature
      pertaining to the prevention of CPSP (>= 2 months after surgery) after
      perioperative administration of gabapentin and pregabalin and (2) performed a
      meta-analysis using studies that report sufficient data. A search of electronic
      databases (Medline, Embase, Cochrane Central Register of Controlled Trials,
      Cochrane Database of Systematic Reviews, IPA, and CINAHL) for relevant English
      language trials to June 2011 was conducted. METHODS: The following inclusion
      criteria for identified clinical trials were used for entry into the present
      systematic review: randomization; double-blind assessments of pain and analgesic
      use; report of pain using a reliable and valid measure; report of analgesic
      consumption; and an absence of design flaws, methodological problems or
      confounders that render interpretation of the results ambiguous. Trials that did
      not fit the definition of preventive analgesia and did not assess chronic pain at
      2 or more months after surgery were excluded. RESULTS: The database search
      yielded 474 citations. Eleven studies met the inclusion criteria. Of the 11
      trials, 8 studied gabapentin, 4 of which (i.e., 50%) found that perioperative
      administration of gabapentin decreased the incidence of chronic pain more than 2
      months after surgery. The 3 trials that used pregabalin demonstrated a
      significant reduction in the incidence of CPSP, and 2 of the 3 trials also found
      an improvement in postsurgical patient function. Eight studies were included in a
      meta-analysis, 6 of the gabapentin trials demonstrated a moderate-to-large
      reduction in the development of CPSP (pooled odds ratio [OR] 0.52; 95% confidence
      interval [CI], 0.27 to 0.98; P = 0.04), and the 2 pregabalin trials found a very
      large reduction in the development of CPSP (pooled OR 0.09; 95% CI, 0.02 to 0.79;
      P = 0.007). CONCLUSIONS: The present review supports the view that perioperative
      administration of gabapentin and pregabalin are effective in reducing the
      incidence of CPSP. Better-designed and appropriately powered clinical trials are
      needed to confirm these early findings.

PMID- 22415536
TI  - Exercise training attenuates neuropathic pain and cytokine expression after
      chronic constriction injury of rat sciatic nerve.
AB  - BACKGROUND: The underlying mechanism of exercise on neuropathic pain is not well
      understood. We investigated whether physical exercise regulates the functional
      recovery and heat shock protein 72 (Hsp72), tumor necrosis factor-alpha (TNF
      alpha), and interlukin-1beta (IL-1beta) expression after chronic constriction
      injury (CCI) of the sciatic nerve. METHODS: Male Sprague-Dawley rats were divided
      into 7 groups: control, sham operated (SO), SO with swimming or treadmill
      exercise (SOSE or SOTE), CCI, CCI with swimming or treadmill exercise (CCISE or
      CCITE). We recorded body weight, thermal withdrawal latency, and mechanical
      withdrawal threshold as well as Hsp72, TNF-alpha, and IL-1beta expression in
      sciatic nerve. RESULTS: The body weights in the control and SO groups were
      heavier than those in the SOSE, SOTE, CCI, CCISE, and CCITE groups. CCI rats with
      swimming or treadmill exercise showed significant increase in thermal withdrawal
      latency and mechanical withdrawal threshold when compared with CCI rats without
      exercise on day 21 after CCI. Both CCISE and CCITE groups demonstrated greater
      Hsp72 expression and lower TNF-alpha or IL-1beta level than did the CCI group in
      sciatic nerve on day 21 after CCI. CONCLUSIONS: These results suggest that
      progressive exercise training decreases peripheral neuropathic pain as well as
      TNF-alpha and IL-1beta overproduction and increases HSP72 expression after CCI of
      the sciatic nerve.

PMID- 22415537
TI  - Propofol wastage in anesthesia.
AB  - BACKGROUND: Drug waste has been implicated as a significant contributor to
      environmental contamination and unnecessary health care costs. METHODS: We
      collected the contents of pharmaceutical waste collection containers in each of 8
      operating rooms, sorted them by hand, and tabulated the results. Propofol
      returned to the pharmacy was not counted as wasted drug. RESULTS: Wasted or
      discarded propofol accounted for 45% of all the drug waste. CONCLUSIONS: Propofol
      does not degrade in nature, accumulates in body fat, and is toxic to aquatic
      life. We reduced wastage by removing 50 and 100 mL vials of propofol from the
      pharmacy, retaining only the smallest size (20 mL).

PMID- 22415538
TI  - [Diagnosis and management of pain syndromes following parotidectomy].
AB  - The preservation of the great auricular nerve in parotid gland surgery for benign
      disease is discussed controversially. The negative impact on quality of life due
      to lack of sensation in the auricle was underestimated in former times. Thus,
      more and more surgeons try to preserve the nerve with rising incidence of
      possible complications like neuralgia. We report on three patients with
      postoperative neuralgia of the great auricular nerve. Two patients experienced a
      long lasting remission of their neuralgia after an infiltration of the punctum
      nervosum with a local anesthetic. In a third patient the great auricular nerve
      had to be resected 6 months after parotidectomy. Other options of therapy are
      described.

PMID- 22415540
TI  - Binuclear rhenium(I) complexes for the photocatalytic reduction of CO2.
AB  - Binuclear rhenium(I) complexes with 1,2-bis(4,4'-methyl-[2,2']bipyridyl)-ethane
      and 1,2-bis(4,4'-methyl-[2,2']bipyridyl)-dodecane as bridging ligands and their
      mononuclear analogues have been synthesized and characterized by their
      spectroscopic and electrochemical properties. First reduction potentials and
      luminescence properties as well as the reductive quenching of the emissive state
      with TEOA were not affected by the alkyl linker. By means of a detailed
      comparison of the photocatalytic CO(2) reductions of the monometallic and the
      bimetallic complexes a great beneficial effect on the activity depending on the
      proximity of the centres was found. In high dilution the overall kinetics in the
      CO(2) photoreduction of mononuclear complexes are clearly monometallic. If the
      proximity of the centres is adjusted according to the lifetime of the OER (one
      electron reduced species) the photocatalytic activity is greatly improved showing
      a clear bimetallic mechanism. In the binuclear rhenium complexes, both the facile
      generation of a free coordination site and binuclear interactions for effective
      two electron transfer can be realized.

PMID- 22415539
TI  - Adipose tissue as regulator of vascular tone.
AB  - Adipokines secreted by visceral, subcutaneous, and perivascular adipocytes are
      involved in the regulation of vascular tone by acting as circulatory hormones
      (leptin, adiponectin, omentin, visfatin, angiotensin II, resistin, tumor necrosis
      factor-alpha, interleukin-6, apelin) and/or via local paracrine factors
      (perivascular adipocyte-derived relaxing and contractile factors). Vascular tone
      regulation by adipokines is compromised in obesitas and obesity-related
      disorders. Hypoxia created in growing adipose tissue dysregulates synthesis of
      vasoactive adipokines in favor of harmful proinflammatory adipokines, while the
      levels of the cardioprotective adipokines adiponectin and omentin decrease.
      Considering the potential of the role of adipokines in obesity-related vascular
      diseases, strategies to counter these diseases by targeting the adipokines are
      discussed.

PMID- 22415541
TI  - Genetic characterization of Aleutian mink disease viruses isolated in China.
AB  - Aleutian mink disease virus (AMDV) is a parvovirus that causes an immune complex
      mediated disease in minks. To understand the genetic characterization of AMDV in
      China, the genomic sequences of three isolates, ADV-LN1, ADV-LN2, and ADV-LN3,
      from different farms in the Northern China were analyzed. The results showed that
      the lengths of genomic sequences of three isolates were 4,543, 4,566, and 4,566
      bp, respectively. They shared only 95.5-96.3 % nucleotide identity with each
      other. The nucleotide and amino acid homology of genome sequence between the
      Chinese isolates and European or American strains (ADV-G, ADV-Utah1, and ADV-SL3)
      were 92.4-95.0 % and 92.1-93.8 %, respectively. The amino acid substitutions
      randomly distributed in the genome, especially NS gene. ADV-LN1 strain had a 9
      amino-acid deletion at amino acid positions 70 and 72-79 in the VP1 gene,
      comparing with ADV-G strain; ADV-LN2 and ADV-LN3 strains had 1-amino-acid
      deletion at amino acid positions 70 in the VP1. Some potential glycosylation site
      mutations in VP and NS genes were also observed. Phylogenetic analysis results
      showed that the three strains belonged to two different branches based on the
      complete coding sequence of VP2 gene. However, they all were in the same group
      together with the strains from United States based on the NS1 sequence. It
      indicated that Chinese AMDV isolates had genetic diversity. The origin of the
      ancestors of the Chinese AMDV strains might be associated with the American
      strains.

PMID- 22415542
TI  - Phylogenetic analysis of the VP2 gene of Aleutian mink disease parvoviruses
      isolated from 2009 to 2011 in China.
AB  - Aleutian mink disease parvovirus (AMDV) is a non-enveloped virus with a single
      stranded DNA genome that causes a fatal, usually persistent immune complex
      disease in minks. In this study, a total of 18,654 serum samples were collected
      from minks that were farmed in China from 2009 to 2011. After testing by counter
      current immunoelectrophoresis (CIE), the seroprevalence of AMDV was found to be
      68.67 %. The results show that there is a serious epidemic among Chinese minks
      used for breeding. To gain detailed information regarding the molecular
      epidemiology of AMDV in China, nine strains of AMDV were isolated from mink
      samples that were collected from four of the primary mink farming areas in China.
      The full-length capsid protein VP2 gene from each strain was sequenced after PCR
      amplification, and a phylogenetic analysis was performed on the VP2 gene
      sequence, including the VP2 genes from the other 10 AMDV strains available in the
      GenBank database, which were submitted from the 1970s to 2009. The phylogenetic
      analysis showed that the AMDV isolates were divided into five independent clades.
      The Chinese AMDV strains were distributed among all five groups and showed a high
      level of genetic diversity. Over 50 % of the Chinese AMDV strains were classified
      into two clades that consisted only of isolates from China and that were distinct
      from AMDV strains found in other countries. This finding indicated that both
      local and imported ADMV species are prevalent in the Chinese mink farming
      population.

PMID- 22415543
TI  - Reproducibility of qualitative assessment of stent struts coverage by optical
      coherence tomography.
AB  - Assessment of stent strut coverage by optical coherence tomography (OCT) is not
      standardized. The methodology most commonly used is based on a visual binary
      qualitative assessment (strut covered or not). However, the influence of
      magnification (zoom setting) to the inter- and intra-observer agreements has not
      yet been evaluated. Aim of our study was therefore to evaluate the agreements of
      this approach, taking into account various zoom settings. 126 struts from 10
      selected frames were independently evaluated by four observers using a stepwise
      approach increasing the zoom setting as following: (1) full view of the lumen
      (FV), (2) half view of the lumen (HV) and (3) a quarter view of the lumen (QV).
      Intra- and inter-observer agreements (kappa) were assessed. The rate of
      uncoverage was determined for each strut as the number of times it was defined as
      uncovered divided by the total number of observations (maximum 12 = 3 zoom
      settings * 4 analysts) and expressed as percentage. The inter-observer kappa
      values (mean [range]) were 0.32 [0.07-0.63], 0.40 [0.18-0.69] and 0.33 [0.09
      0.6], within FV, HV and QV respectively. The intra-observer kappa values were
      0.60 [0.50-0.70], 0.75 [0.75-0.76] and 0.60 [0.50-0.70], within FV, HV and QV
      respectively. By increasing zoom setting the kappa value of intra-observer
      agreement was 0.74 [0.58-0.83] (from FV to HV), 0.70 [0.56-0.83] (from HV to QV)
      and 0.70 [0.37-0.86] (from FV to QV). Overall, the rate of uncoverage was 15.5%
      [8.3-100%]. The OCT qualitative evaluation of strut coverage has wide inter and
      intra-observer agreements and is dependent of the zoom setting used during the
      analysis. A more reproducible approach would be needed to eventually increase the
      probability to link uncovered struts with clinical events.

PMID- 22415544
TI  - MDCK cell-cultured influenza virus vaccine protects mice from lethal challenge
      with different influenza viruses.
AB  - Influenza epidemics are major health concern worldwide. Vaccination is the major
      strategy to protect the general population from a pandemic. Currently, most
      influenza vaccines are manufactured using chicken embroynated eggs, but this
      manufacturing method has potential limitations, and cell-based vaccines offer a
      number of advantages over the traditional method. We reported here using the
      scalable bioreactor to produce pandemic influenza virus vaccine in a Madin-Darby
      canine kidney cell culture system. In the 7.5-L bioreactor, the cell
      concentration reached to 3.2 * 10(6) cells/mL and the highest virus titers of 256
      HAU/50 MUL and 1 * 10(7) TCID50/mL. The HA concentration was found to be 11.2
      MUg/mL. The vaccines produced by the cell-cultured system induced neutralization
      antibodies, cross-reactive T-cell responses, and were protective in a mouse model
      against different lethal influenza virus challenge. These data indicate that
      microcarrier-based cell-cultured influenza virus vaccine manufacture system in
      scalable bioreactor could be used to produce effective pandemic influenza virus
      vaccines.

PMID- 22415545
TI  - (1)H, (13)C and (15)N resonance assignments of the periplasmic signalling domain
      of HasR, a TonB-dependent outer membrane heme transporter.
AB  - TonB-dependent transporters (TBDTs) are bacterial outer membrane proteins that
      internalize nutrients such as vitamin B12, metal complexes, heme, some
      carbohydrates, etc. In addition to their transport activity, several TBDTs are
      also involved in a signalling cascade from the cell surface into the cytoplasm,
      via their periplasmic signalling domain. Here we report the backbone and side
      chain resonance assignments of the signalling domain of HasR, a TonB-dependent
      outer membrane heme transporter from Serratia marcescens as a first step towards
      its structural study.

PMID- 22415546
TI  - Aliphatic (1)H, (13)C and (15)N chemical shift assignments of dihydrofolate
      reductase from the psychropiezophile Moritella profunda in complex with NADP(+)
      and folate.
AB  - Dihydrofolate reductase from the deep-sea bacterium Moritella profunda (MpDHFR)
      has been (13)C/(15)N isotopically labelled and purified. Here, we report the
      aliphatic (1)H, (13)C and (15)N resonance assignments of MpDHFR in complex with
      NADP(+) and folate. The spectra of MpDHFR suggest considerably greater
      conformational heterogeneity than is seen in the closely related DHFR from
      Escherichia coli.

PMID- 22415547
TI  - Water-clustering in hygroscopic ionic liquids-an implicit solvent analysis.
AB  - Most ionic liquids are known to be hygroscopic to varying degrees, and that can
      be detrimental or useful depending upon the application in question. Water can
      accumulate slowly over hours or days to saturation levels corresponding to the
      humidity level. When designing or deploying a new ionic liquid it is important to
      be able to estimate its maximum moisture absorbing ability at the temperature and
      pressure of its operation. With this goal in mind we have carried out
      computational studies on three ionic liquid systems based on [BF(4)](-), [PF(6)](
      ), and [Tf(2)N](-) anions and 1-alkyl-3-methyl-imidazolium ([C(n)mim](+)) cations
      within an implicit solvent formalism. For highly hygroscopic systems like
      [C(n)mim][BF(4)] we find that non-iterative calculations with single water
      molecules can lead to significant underestimation of the maximum moisture
      content, while iterative calculations can result in miscibility behavior
      qualitatively different from experimental observations. On the other hand, the
      inclusion of small hydrogen-bonded water-clusters up to an appropriately chosen
      size is shown to yield better quantitative agreements with experimentally
      observed water uptake. Additionally, such calculations appear consistent with a
      number of thermodynamically interesting phase behaviors, including limited
      solubility to full-miscibility transitions as a function of temperature and as a
      function of the alkyl chain length of the imidazolium cation. For hydrophobic
      systems like [C(n)mim][PF(6)] and [C(n)mim][Tf(2)N] the computed solubility (for
      each n) is found to have a smooth convergence behavior as a function of the
      largest cluster-size considered with the results for the larger clusters being
      close to that obtained by iterative calculations with single water molecules.

PMID- 22415548
TI  - Monomeric adenine decay dynamics influenced by the DNA environment.
AB  - We report on-the-fly surface-hopping dynamics simulations of single adenine
      embedded in solvated DNA oligomers, (dA)10 and (dA)10.(dT)10. Both model systems
      are found to decay from the S1 to the S0 state via distinct monomeric channels,
      on account of the strong hydrogen-bonding interactions between the Watson-Crick
      pair in the double-stranded oligomer. Surprisingly, the decay times (several
      picoseconds) for the current models are 10 times longer than those of adenine in
      the gas or aqueous phase, while matching one of the time constants observed
      experimentally. We discuss possible reasons for these longer decay times,
      including steric hindrance in the DNA strands, electronic effects of the
      environment, and the presence of other local excited-state minima. We present
      optimized geometries and relative energies for representative S0 and S1 minima as
      well as conical intersections related to the hopping events. We have also
      computed steady-state and time-dependent fluorescence spectra that may help
      understand the experimental observations.

PMID- 22415549
TI  - Fabrication and characterization of nanostructured titania films with integrated
      function from inorganic-organic hybrid materials.
AB  - Nanostructured titania films are of growing interest due to their application in
      future photovoltaic technologies. Therefore, a lot of effort has been put into
      the controlled fabrication and tailoring of titania nanostructures. The
      controlled sol-gel synthesis of titania, in particular in combination with block
      copolymer templates, is very promising because of its high control on the
      nanostructure, easy application and cheap processing possibilities. This tutorial
      review gives a short overview of the structural control of titania films gained
      by using templated sol-gel chemistry and shows how this approach is extended by
      the addition of further functionality to the films. Different expansions of the
      sol-gel templating are possible by the fabrication of gradient samples, by the
      addition of a homopolymer, by the combination with micro-fluidics and also by the
      application of novel precursors for low-temperature processing. Moreover,
      hierarchically structured titania films can be fabricated via the subsequent
      application of several sol-gel steps or via the inclusion of colloidal templates
      in a one-step process. Integrated function in the block copolymer used in the sol
      gel synthesis allows for the fabrication of an integrated blocking layer or an
      integrated hole-conductor. Both approaches grant a one-step fabrication of two
      components of a working solar cell, which make them very promising towards a
      cheap solar cell production route. Looking to the complete solar cell, the top
      contact is also of great importance as it influences the function of the whole
      solar cell. Thus, the mechanisms acting in the top contact formation are also
      reviewed. For all these aspects, characterization techniques that allow for a
      structural investigation of nanostructures inside the active layers are
      important. Therefore, the characterization techniques that are used in real space
      as well as in reciprocal space are explained shortly as well.

PMID- 22415550
TI  - Large-scale recording of neurons by movable silicon probes in behaving rodents.
AB  - A major challenge in neuroscience is linking behavior to the collective activity
      of neural assemblies. Understanding of input-output relationships of neurons and
      circuits requires methods with the spatial selectivity and temporal resolution
      appropriate for mechanistic analysis of neural ensembles in the behaving animal,
      i.e. recording of representatively large samples of isolated single neurons.
      Ensemble monitoring of neuronal activity has progressed remarkably in the past
      decade in both small and large-brained animals, including human subjects.
      Multiple-site recording with silicon-based devices are particularly effective
      because of their scalability, small volume and geometric design. Here, we
      describe methods for recording multiple single neurons and local field potential
      in behaving rodents, using commercially available micro-machined silicon probes
      with custom-made accessory components. There are two basic options for
      interfacing silicon probes to preamplifiers: printed circuit boards and flexible
      cables. Probe supplying companies (http://www.neuronexustech.com/;
      http://www.sbmicrosystems.com/; http://www.acreo.se/) usually provide the bonding
      service and deliver probes bonded to printed circuit boards or flexible cables.
      Here, we describe the implantation of a 4-shank, 32-site probe attached to
      flexible polyimide cable, and mounted on a movable microdrive. Each step of the
      probe preparation, microdrive construction and surgery is illustrated so that the
      end user can easily replicate the process.

PMID- 22415551
TI  - Modelling the site of bromide binding in vanadate-dependent bromoperoxidases.
AB  - Treatment of Boc-protected (S)-serine (Ser) methyl ester with triphenylphosphine
      bromide Ph(3)PBr (intermittently generated from PPh(3) and N-bromosuccinimide)
      yields Boc-3-bromoalanine (R)-Boc-BrAlaMe and, after deprotection, bromoalanine
      methyl ester (R)-BrAlaMe in the form of its hydrobromide. Boc-BrAlaMe and BrAlaMe
      have been structurally characterised. The reaction between BrAlaMe,
      salicylaldehyde (sal) and VO(2+) results in the formation of Schiff base
      complexes of composition [VO(sal-BrAlaMe)solv](+) (solv = CH(3)OH: 3, THF: 5) and
      [VO(sal-BrAla)THF] 4. DFT calculations of the structures of 3, 4 and 5, based on
      the B3LYP functional and employing the triple zeta basis set 6-311++g(d,p),
      provide distances Br...V = 4.0 +/- 0.1 A, if some distortion of the dihedral
      angle ?N-C-C-Br is allowed (affording a maximum energy of ca. 45 kJ mol(-1)), and
      thus model Br...V distances detected by X-ray methods in bromoperoxidases from
      the marine algae Ascophyllum nodosum and Corallina pilulifera. The DFT
      calculations have been validated by comparing calculated and found structures,
      including the new complex [V(V)O(Amp-sal)OMe(MeOH)] (1, Amp is the aminophenol
      moiety) and the known complex [VO(L-Ser-van)H(2)O] (van = vanillin). Additional
      validation has been undertaken by checking experimental against calculated
      (BHandHLYP) EPR spectroscopic hyperfine coupling constants. Complexes containing
      bromine as a substituent at the phenyl moiety of a Schiff base ligand do not
      allow for an appropriate simulation of the Br...V distance in peroxidases. The
      closest agreement, d(Br...V) = 4.87 A, is achieved with [VO(3Br-salSer)THF] (6),
      where 3Brsal-Ser is the dianionic Schiff base formed between 3-Br-5-NO(2)
      salicylaldehyde and serine.

PMID- 22415552
TI  - Production, characterization and antioxidant activity of exopolysaccharides from
      submerged culture of Morchella crassipes.
AB  - The aim of this work was to investigate the fermentation optimization, molecular
      characterization, and antioxidant activity in vitro of exopolysaccharides (EPS)
      from Morchella crassipes in submerged culture. Firstly, an optimal medium for EPS
      production was obtained by single-factor experiment and central composite design
      as follows: maltose 44.79 g/L and tryptone 4.21 g/L. Then, one fraction of EPS
      was obtained from the culture filtrates by size exclusion chromatography and the
      molecular characteristics were examined by a multi-angle laser light scattering
      and refractive index detector system. The weight-average molar mass and the
      polydispersity ratio of the EPS fraction were revealed to be 1.961 * 10(4) g/mol
      and 1.838, respectively. FT-IR spectroscopy was used for obtaining vibrational
      spectra of the purified EPS fraction. Finally, the antioxidant activity of EPS
      was investigated and the relationship with molecular properties was discussed as
      well.

PMID- 22415554
TI  - Delineating compartmentalized control of phenylpropanoid metabolism.

PMID- 22415553
TI  - Optimal induction of myeloma cell death requires dual blockade of
      phosphoinositide 3-kinase and mTOR signalling and is determined by translocation
      subtype.
AB  - Novel inhibitors of PI3K, Akt and mTOR have been developed recently, some of
      which have entered clinical trials. Although such compounds inhibit cell
      proliferation, their effects on cell survival, an important determinant of
      clinical response, are less distinct. Using a broad panel of myeloma cell lines
      and primary patient samples, we show that dual PI3K and mTOR inhibition can
      induce cell death. The effects are most marked in cells expressing the t(4;14)
      translocation, whereas t(11;14) cells are largely resistant. Using specific
      inhibitors of individual pathway components, we show that optimal induction of
      cell death requires inhibition of both PI3K and mTOR. This is due to a PI3K
      independent component of mTOR activation downstream of the MAP kinase pathway.
      Novel mTOR kinase inhibitors, which block both TORC1 and TORC2 complexes thereby
      also reducing Akt activity, are less effective than dual PI3K/mTOR inhibitors
      because of feedback activation of PI3K signalling. Dual PI3K/mTOR inhibitors
      sensitise t(4;14) and t(14;16), but not t(11;14), expressing cells to the
      cytotoxic effects of dexamethasone. We have identified a robust cytogenetic
      biomarker for response to PI3K/mTOR inhibition--these results will inform the
      design and prioritisation of clinical studies with novel inhibitors in genetic
      subgroups of myeloma.

PMID- 22415555
TI  - Letter from the editor-in-chief.

PMID- 22415556
TI  - LaCoO3 acting as an efficient and robust catalyst for photocatalytic water
      oxidation with persulfate.
AB  - Cobalt-containing metal oxides [perovskites (LaCoO(3), NdCoO(3), YCoO(3),
      La(0.7)Sr(0.3)CoO(3)), spinel (Co(3)O(4)) and wolframite (CoWO(4))] have been
      examined as catalysts for photocatalytic water oxidation with Na(2)S(2)O(8) and
      [Ru(bpy)(3)](2+) as an electron acceptor and a photosensitizer, respectively.
      Catalysts with the perovskite structure exhibited higher catalytic activity as
      compared with the catalysts with the spinel and wolframite structures. LaCoO(3),
      which stabilizes Co(III) species in the perovskite structure, exhibited the
      highest catalytic activity in the photocatalytic water oxidation compared with
      CoWO(4), Co(3)O(4) and La(0.7)Sr(0.3)CoO(3) which contain Co(II) or Co(IV)
      species in the matrices. The high catalytic reactivity of LaCoO(3) possessing
      perovskite structure was maintained in NdCoO(3) and YCoO(3) which exclusively
      contain Co(III) species. Thus, the catalytic activity of Co ions can be
      controlled by the additional metal ions, which leads to development of highly
      reactive and robust catalysts for the photocatalytic water oxidation.

PMID- 22415559
TI  - Music making for health, well-being and behaviour change in youth justice
      settings: a systematic review.
AB  - Youth justice is an important public health issue. There is growing recognition
      of the need to adopt effective, evidence-based strategies for working with young
      offenders. Music interventions may be particularly well suited to addressing risk
      factors in young people and reducing juvenile crime. This systematic review of
      international research seeks to contribute to the evidence base on the impact of
      music making on the health, well-being and behaviour of young offenders and those
      considered at risk of offending. It examines outcomes of music making identified
      in quantitative research and discusses theories from qualitative research that
      might help to understand the impact of music making in youth justice settings.

PMID- 22415557
TI  - Ribosomal protein L11 is related to brain maturation during the adult phase in
      Apis cerana cerana (Hymenoptera, Apidae).
AB  - Ribosomal proteins (RPs) play pivotal roles in developmental regulation. The loss
      or mutation of ribosomal protein L11 (RPL11) induces various developmental
      defects. However, few RPs have been functionally characterized in Apis cerana
      cerana. In this study, we isolated a single copy gene, AccRPL11, and
      characterized its connection to brain maturation. AccRPL11 expression was highly
      concentrated in the adult brain and was significantly induced by abiotic stresses
      such as pesticides and heavy metals. Immunofluorescence assays demonstrated that
      AccRPL11 was localized to the medulla, lobula and surrounding tissues of
      esophagus in the brain. The post-transcriptional knockdown of AccRPL11 gene
      expression resulted in a severe decrease in adult brain than in other tissues.
      The expression levels of other brain development-related genes, p38, ERK2, CacyBP
      and CREB, were also reduced. Immunofluorescence signal attenuation was also
      observed in AccRPL11-rich regions of the brain in dsAccRPL11-injected honeybees.
      Taken together, these results suggest that AccRPL11 may be functional in brain
      maturation in honeybee adults.

PMID- 22415560
TI  - Success criteria in pediatric neuroendoscopic procedures. Proposal for
      classification of results after 67 operations.
AB  - PURPOSE: Controversial issues exist concerning criteria for patient selection and
      long-term success in pediatric neuroendoscopic procedures. We designed a
      classification of success grades applicable to high-pressure and chronic
      hydrocephalus and also to those cases in which different endoscopic maneuvers are
      performed during the same procedure. We then evaluated the success rate and
      complications in our series. METHODS: A total of 59 patients underwent 67
      neuroendoscopic procedures between January 2003 and January 2011. A retrospective
      study was made of the preoperative history, operative reports, and postoperative
      imaging findings and medical records. A 5-grade scale was developed to assess the
      type of success depending on clinical and radiological data. Complications
      related to the surgical procedure were also recorded. RESULTS: Two patients were
      excluded from the success analysis due to insufficient follow-up time. The final
      results for the first procedures in 57 patients were complete and permanent
      success (grade I) in 49.1%, complete but transitory success (grade II) in 10.5%,
      partial success (grade III) in 12.3%, doubtful success (grade IV) in 5.3%, and
      failure (grade V) in 22.8%. In eight cases a second procedure followed the
      failure of the first: grade I success was achieved in seven cases (87.5%) and
      grade V in one case (12.5%). The highest success rates were achieved in cases of
      hydrocephalus caused by tumors or arachnoid cysts and the lowest in slit
      ventricle syndrome. CONCLUSIONS: A common classification of degrees of success,
      such as that proposed here, would aid the development of comparative and
      cooperative studies.

PMID- 22415561
TI  - Monitoring heavy metal pollution by aquatic plants: a systematic study of copper
      uptake.
AB  - INTRODUCTION: The copper bioaccumulation by the floating Lemna minor and by the
      completely submerged Ranunculus tricophyllus as a function of exposure time and
      copper concentration was studied, with the aim of proposing these species as
      environmental biosensors of the water pollution. RESULTS: The results show that
      both these aquatic angiosperms are good indicators of copper pollution because
      the copper uptake is the only function of metal concentration (water pollution).
      CONCLUSION: Uptake behavior is reported as a function of the time and
      concentration, based on the results of a 3-year study. Kinetic evaluations are
      proposed.

PMID- 22415562
TI  - Reconciling subjective memory complaints with objective memory performance in the
      menopausal transition.
AB  - OBJECTIVE: The overall aim of this study was to examine the relationship between
      subjective memory complaints and objective cognitive performance in
      perimenopausal women. The specific aims were to determine (1) if subjective
      complaints of memory problems relate to objective performance on memory tests,
      (2) if subjective complaints of memory problems relate to other domains of
      cognitive function, and (3) if subjective memory complaints relate to other
      noncognitive factors, such as depression, anxiety, and sleep quality. METHODS:
      Seventy-five perimenopausal women completed a comprehensive neuropsychological
      battery, which included measures of attention, working memory, verbal memory,
      verbal fluency, visuospatial skill, and fine motor dexterity; completed self
      report inventories of their perceived memory and menopausal symptoms; and
      provided serum levels of estradiol and follicle-stimulating hormone. RESULTS:
      Memory complaints were not associated with verbal learning or verbal memory but
      were associated with working memory and complex attention/vigilance. Memory
      complaints were also associated with symptoms of depression, anxiety, somatic
      complaints, and sleep disturbance. Regression analyses revealed that memory
      complaints were best predicted by depressive symptoms, somatic complaints, and
      working memory performance. CONCLUSIONS: Memory complaints in the menopausal
      transition may reflect true difficulties with attentionally mediated cognitive
      processes. Memory complaints may also be associated with other menopausal-related
      symptoms.

PMID- 22415563
TI  - Androstenediol complements estrogenic bioactivity during the menopausal
      transition.
AB  - OBJECTIVE: The perimenopausal increase in circulating dehydroepiandrosterone
      sulfate (DHEAS) levels during the menopausal transition (MT) is accompanied by
      other adrenal steroids that have the potential to alter estrogen/androgen balance
      and explain the wide interwoman range of estrogen-related symptoms experienced
      during the MT. METHODS: Annual serum samples from the Study of Women's Health
      Across the Nation, which had previously been analyzed for immunoreactive
      estradiol (E2), testosterone, DHEAS, and sex hormone-binding globulin, were
      selected based on DHEAS concentration and analyzed for immunoreactive and
      bioactive estrogens and androgens, including immunoreactive androstenedione,
      dehydroepiandrosterone, and 5-androstene-3beta,17beta-diol (androstenediol
      [Adiol]). RESULTS: A two-fold increase in circulating androstenedione and
      testosterone was found to rise in parallel with the rise in circulating DHEAS,
      whereas dehydroepiandrosterone and Adiol concentrations rose seven- to eight
      fold. Circulating Adiol, which has both androgenic and estrogenic biological
      activity, was significantly associated (P < 0.02) with circulating estrogen
      bioactivity only when E2 concentrations were low and Adiol levels were high.
      CONCLUSIONS: The wide range of circulating levels of Adiol and its contribution
      to total circulating estrogenicity during the MT is consistent with the observed
      interwoman difference in symptoms at this time. Therefore, we conclude that Adiol
      contributes to circulating estrogenicity when E2 production falls at menopause
      and may contribute significantly to the endocrine changes experienced by midlife
      women.

PMID- 22415564
TI  - Multimorbidity and associated factors in Brazilian women aged 40 to 65 years:  a
      population-based study.
AB  - OBJECTIVE: The aim of this study was to evaluate the presence of multimorbidity
      and associated factors in Brazilian women aged 40 to 65 years with 11 or more
      years of school education. METHODS: A secondary analysis of a cross-sectional
      population-based study was conducted using an anonymous self-report questionnaire
      completed by 377 women. The number of reported morbid conditions was evaluated
      (depression, hypertension, diabetes mellitus, urinary incontinence, and insomnia)
      and classified as none or one and two or more morbid conditions. The
      sociodemographic, behavioral, clinical, and reproductive factors associated with
      these conditions were also assessed. The chi test and multiple logistic
      regression analysis with stepwise selection criteria were used to select the
      major factors associated with morbid conditions, with a significance level set at
      5%. RESULTS: Insomnia was reported by 38.5%, depression by 31%, hypertension by
      28.4%, urinary incontinence by 23.2%, and diabetes by 6.3% of the participants.
      In this sample, 28.9% did not report any morbid conditions, 31.8% reported one
      morbid condition, and 39.3% reported two or more morbid conditions. On logistic
      regression analysis, the increased likelihood of having two or more morbid
      conditions was associated with bad/fair self-perception of health (increased 5.1
      times; 95% CI, 1.85-14.1), nonperformance of physical activity (increased by 2.7
      times; 95% CI, 1.08-6.81), obesity (increased by 30.3 times; 95% CI, 3.17-250),
      postmenopause (increased by 4.4 times; 95% CI, 1.57-12.11), and nervousness
      (increased by 3.8 times; 95% CI, 1.45-9.8). CONCLUSIONS: A worse self-perception
      of health, sedentariness, obesity, nervousness, and being postmenopausal were
      associated with multimorbidity.

PMID- 22415565
TI  - Estrogen deficiency accelerates aging of the optic nerve.
AB  - The aim of this study was to provide a comprehensive review on hormone-based
      pathophysiology of aging of the optic nerve and glaucoma, including a literature
      review and expert opinions. Glaucoma, a group of intraocular pressure-related
      optic neuropathies, is characterized by the slow progressive neurodegeneration of
      retinal ganglion cells and their axons, resulting in irreversible visual
      sensitivity loss and blindness. Increasing evidence suggests that glaucoma
      represents the accelerated aging of the optic nerve and is a neurodegenerative
      disease of the central nervous system. This review highlights the high burden of
      glaucoma in older women and the importance of understanding the hormone-related
      pathophysiology of optic nerve aging and glaucoma in women. Strong
      epidemiological, clinical, and experimental evidence supports the proposed
      hypothesis that early loss of estrogen leads to premature aging and increased
      susceptibility of the optic nerve to glaucomatous damage. Future investigations
      into the hormone-related mechanisms of aging and glaucoma will support the
      development of novel sex-specific preventive and therapeutic strategies in
      glaucoma.

PMID- 22415566
TI  - Association of sex hormones and sex hormone-binding globulin with depressive
      symptoms in postmenopausal women:  the Multiethnic Study of Atherosclerosis.
AB  - OBJECTIVE: Sex hormones are thought to play an important role in the
      pathophysiology of depressive disorders in women. This study assessed the
      associations of total testosterone (T), bioavailable T, estradiol,
      dehydroepiandrosterone, and sex hormone-binding globulin (SHBG) with depressive
      symptoms stratified on postmenopausal stage to determine whether the associations
      were strongest for early postmenopausal women. METHODS: Women (N = 1,824) free of
      depressive symptoms at baseline (2000-2002) in the Multiethnic Study of
      Atherosclerosis were categorized into tertiles of years postmenopause: T1, 0 to
      10 years; T2, 11 to 20 years; and T3, 21 to 58 years. Multivariable-adjusted
      relative risks (RRs) and 95% CIs were computed for the incidence of depressive
      symptoms, as defined by a score of 16 or higher on the Center for Epidemiologic
      Studies Depression scale at examination 3 (2004-2005). RESULTS: In analysis
      including all sex hormones, the RR for incident depressive symptoms associated
      with 1 unit higher log total T was 0.57 (P = 0.13), with log estradiol was 0.78
      (P = 0.04), with log SHBG was 1.84 (P = 0.003), and with log
      dehydroepiandrosterone was 1.45 (P = 0.08) in T1. Without adjustment for SHBG,
      the RR for log bioavailable T was 0.16 (P = 0.04). However, in T2 and T3, there
      were no meaningful associations of hormone or SHBG levels with incident
      depressive symptoms. When stratified by HT use, results were consistent for HT
      users but attenuated for HT nonusers. CONCLUSIONS: In early postmenopausal women,
      sex hormones were associated with incident depressive symptoms.

PMID- 22415567
TI  - Dietary phytoestrogen intakes and cognitive function during the menopausal
      transition:  results from the Study of Women's Health Across the Nation
      Phytoestrogen Study.
AB  - OBJECTIVE: Phytoestrogens, which consist mainly of isoflavones, lignans, and
      coumestans have estrogenic and anti-inflammatory properties. Previous research
      suggests that higher dietary or supplemental intakes of isoflavones and lignans
      are related to better cognitive performance in middle-aged and older women.
      METHODS: We conducted longitudinal analysis of dietary phytoestrogens and
      cognitive performance in a cohort of African American, white, Chinese, and
      Japanese women undergoing the menopausal transition. The tests were Symbol Digit
      Modalities, East Boston Memory, and Digits Span Backward. Phytoestrogens were
      assessed using the Food Frequency Questionnaire. We modeled each cognitive score
      as a function of concurrent value of the primary predictors (highest tertile of
      isoflavones, lignans, or coumestrol) and covariates including the menopausal
      transition stage. RESULTS: Coumestrol and isoflavone intakes were 10 and 25 times
      greater, respectively, in Asian than in non-Asian participants. During late
      perimenopause and postmenopause, Asian women with high isoflavone intakes did
      better on processing speed, but during early perimenopause and postmenopause,
      high-isoflavone Asian consumers performed worse on verbal memory. The highest
      isoflavone consumers among non-Asians likewise posted lower verbal memory scores
      during early perimenopause. A verbal memory benefit of higher dietary lignan
      consumption was apparent only during late perimenopause, when women from all
      ethnic/racial groups who were in the highest tertile of intake demonstrated a
      small advantage. Coumestrol was unrelated to cognitive performance. CONCLUSIONS:
      The cognitive effects of dietary phytoestrogens are small, seem to be class
      specific, vary by menopause stage and cognitive domain, and differ among
      ethnic/racial groups (but whether this is related to dose or to host factors
      cannot be discerned).

PMID- 22415568
TI  - Are vasomotor symptoms associated with sleep characteristics among symptomatic
      midlife women? Comparisons of self-report and objective measures.
AB  - OBJECTIVE: Many women report vasomotor symptoms (VMS) and sleep problems during
      the menopausal transition. Although reported VMS are consistently related to
      reported sleep disturbance, findings using physiologic measures of VMS or sleep
      have been more mixed. Our objective was to examine whether more VMS during sleep
      are associated with poorer sleep among midlife women with VMS using physiologic
      measures of both VMS and sleep. METHODS: A subcohort of participants (N = 52)
      with VMS, a uterus and both ovaries, and free of medications affecting VMS from
      the Pittsburgh site of the Study of Women's Health Across the Nation underwent
      four 24-hour periods of in-home ambulatory VMS and sleep measurement. Measures
      included sternal skin conductance for the measurement of VMS, actigraphy for
      assessing sleep, a VMS diary, and a sleep diary completed before bed and upon
      waking. Associations between VMS and sleep were evaluated using generalized
      estimating equations with covariates age, body mass index, medications affecting
      sleep, race, financial strain, and depressive symptoms. RESULTS: More VMS
      recalled upon waking were associated with significantly lower actigraphy-assessed
      sleep efficiency, significantly higher wakefulness after sleep onset, and
      somewhat longer sleep latency. Conversely, physiologically measured VMS and VMS
      reported during the night were largely unrelated to sleep characteristics.
      CONCLUSIONS: Associations between VMS and sleep may depend more on the awareness
      of and recall of VMS rather than solely on their physiologic occurrence.

PMID- 22415569
TI  - Effects of rosiglitazone on the cardiovascular profile in postmenopausal women
      without diabetes mellitus:  interplay of thiazolidinediones and hormone therapy.
AB  - OBJECTIVE: Thiazolidinediones have antiatherothrombotic effects on persons with
      diabetes. Hormone therapy among postmenopausal women has both positive and
      negative cardiovascular effects. However, the effects of rosiglitazone with or
      without concurrent long-term hormone therapy on the cardiovascular profile of
      nondiabetic postmenopausal women are unknown. METHODS: Thirty-eight nondiabetic
      postmenopausal women were enrolled in this double-blind and placebo-controlled
      study. Eighteen participants received 4 mg rosiglitazone, and 20 participants
      took placebo daily for 12 weeks. Global endothelial function and plasma
      biomarkers were measured. RESULTS: Baseline characteristics and parameters were
      similar between the groups. Rosiglitazone, but not placebo, significantly reduced
      leukocyte count and plasma levels of matrix metalloproteinase-9 and inhibited the
      elevation of plasma levels of plasminogen activator inhibitor-1 and tissue
      plasminogen activator (P < 0.05 for all). Most of the favorable effects provided
      by rosiglitazone were still present in participants with concurrent hormone
      therapy. Increased body weight and waist size as well as elevation of the plasma
      levels of total and low-density lipoprotein cholesterol were noted after
      rosiglitazone treatment among participants without concurrent hormone therapy. No
      significant change in the global endothelial function occurred in response to
      treatment in either group. CONCLUSIONS: Rosiglitazone treatment provided both
      protective and harmful cardiovascular effects in nondiabetic postmenopausal
      women. Concurrent hormone therapy resulted in the maintenance of the major
      beneficial effects while neutralizing the unfavorable effects of rosiglitazone.

PMID- 22415570
TI  - Menopausal transition stage-specific changes in circulating adrenal androgens.
AB  - OBJECTIVE: It is now recognized that mean circulating dehydroepiandrosterone
      sulfate (DHEAS) concentrations in most midlife women exhibit a positive
      inflection starting in early perimenopause, continuing through early
      postmenopause and returning to early perimenopausal levels by late postmenopause.
      This rise in mean DHEAS is accompanied by concomitant rises in testosterone (T),
      dehydroepiandrosteone (DHEA), and androstenedione (Adione) and an equal rise in
      androstenediol (Adiol). These observations suggest that there is a specific
      relationship between the circulating levels of steroids emanating from the
      adrenal glands, declining ovarian function, and the stages of the menopausal
      transition. This study was designed to test the hypothesis that the menopausal
      stage-specific change in circulating DHEAS is associated with concomitant changes
      in the circulating pattern of adrenal steroids and that some of these adrenal
      androgens could influence the circulating estrogen/androgen balance. METHODS:
      Stored annual serum samples (N = 120) were first selected to represent four
      longitudinal DHEAS profiles of individual women to assess and compare changes in
      the adrenal contribution to circulating steroids. RESULTS: Changes in mean
      circulating DHEAS levels in midlife women during the menopausal transition is
      associated with changes in mean circulating T, Adione, and Adiol. Mean Adione and
      T concentrations changed the least, whereas mean DHEAS and Adiol changed the
      most. CONCLUSIONS: Changes in circulating steroid hormone emanating from the
      adrenal during the menopausal transition may be more important than the decline
      in ovarian function in terms of altering the estrogen/androgen balance.

PMID- 22415571
TI  - Preparation of dissolvable albumin stents for vascular anastomosis with a 1.9 um
      laser and in vitro mechanical strength assessments.
AB  - INTRODUCTION: We present a clinically relevant method for producing and
      sterilizing dissolvable albumin stents to provide intraluminal support during
      vascular anastomosis, and a method for photothermally soldering vessels using a
      1.9 um diode laser with a 200-um spot size, albumin solder, and water as the
      chromophore. Our aim in this study was to assess the mechanical integrity of
      soldered vessels, and to determine if gamma-irradiation affected the solubility
      of the stents. MATERIALS AND METHODS: The axial tensile strength and burst
      pressure of 3.75 +/- 0.3 mm inner-diameter vessels soldered with varied swath
      width (1-7 mm), laser power (430-610 mW), solder concentration (22-46%w/w), and
      solder layering (1-3 layers) was tested in vitro. Stent dissolution was monitored
      by weight in blood, and with UV absorbance measurements in phosphate buffered
      saline (PBS). Solubility was measured for stents sterilized by 25 kGy gamma
      irradiation, and stents with varied diameter and wall thickness. RESULTS:
      Optimized soldering parameters yielded tensile strengths of 4.4 +/- 1.2 N and
      burst pressures of 400 +/- 90 mm Hg with stay sutures. Differences in stent
      solubility in blood and PBS were not statistically significant (p = 0.99).
      Sterilization by 25 kGy gamma-irradiation did not cause significant changes (p >
      0.6) in stent solubility, which was primarily volume-dependent. Under simulated
      intravascular flow conditions, 3 mm stents dissolved completely with 2.7 +/- 0.7
      ml/mg. CONCLUSIONS: The results show that fast-dissolving stents can be produced
      reliably using the extrusion technique, and sterilized by gamma-irradiation.
      Without stay sutures, soldered vessels exhibited low tensile strength, but burst
      pressures comparable to sutured vessels. It was concluded that stay sutures would
      be necessary in vivo due to degradation of the tensile strength of soldered
      vessels with exposure to moisture.

PMID- 22415572
TI  - The effect of He-Ne and Ga-Al-As laser light on the healing of hard palate mucosa
      of mice.
AB  - Low-level laser therapy (LLLT) has been used to accelerate wound healing, yet
      questions remain concerning its therapeutic applications. This study aimed to
      compare the healing efficacy of helium-neon (He-Ne) red light (laser) and gallium
      aluminum arsenide (Ga-Al-As) infrared lasers at two different doses on hard
      palate wounds. In a randomized controlled study, 75 adult male mice were divided
      into five groups of 15 each, after undergoing identical surgical procedures; a
      control group, with no laser irradiation; HD1 and HD2 groups, treated with He-Ne
      laser (wavelengths 632.8 nm, power 5 mW, and spot size 0.02 cm(2)) at doses of 4
      J/cm(2) and 7.5 J/cm(2) respectively; and GD1 and GD2 groups, treated with Ga-Al
      As laser (wavelengths 830 nm, peak power 25 mW, and spot size 0.10 cm(2)) at the
      doses of 4 J/cm(2) and 7.5 J/cm(2), respectively. Five animals from each group
      were killed on the third, seventh, and 14 days after surgery, and biopsies were
      made for histological analysis. On the 3rd and 7th day after the surgery, the
      number of polymorphonuclear cells (PMN) in HD1, HD2, GD1, and GD2 groups was
      significantly lower than that of the control group. On the 7th and 14th day, the
      fibroblasts and new blood vessels counts and collagen density fibers in HD1, HD2,
      GD1, and GD2 groups were also significantly higher than that of the control
      groups, and the fibroblast counts and collagen density fibers in HD1 and HD2
      groups were higher than that of the GD1 and GD2 groups. LLLT with He-Ne laser
      compared to Ga-Al-As laser has a positive healing effect on hard palate gingival
      wounds in mice regardless of the radiation dose.

PMID- 22415573
TI  - Optical features for chronological aging and photoaging skin by optical coherence
      tomography.
AB  - The characteristics of skins in different aging processes were obtained by
      optical coherence tomography (OCT) single scattering model, and their optical
      parameters were analyzed quantitatively. Significant differences were found in
      epidermis thickness and attenuation coefficients in chronological aging skins and
      photonaging skins. These parameters can be served as indicators of skin type as
      well as the progress of aging. These results are valuable to the study of aging
      skin, and they could further help to understand the mechanism of aging.

PMID- 22415574
TI  - Infrared low-level diode laser on serum chemokine MCP-1 modulation in mice.
AB  - The effect of the low-level laser therapy (LLLT) in the modulation of cells
      related to inflammatory processes has been widely studied, with different
      parameters. The objective was to investigate the immediate and cumulative effect
      of infrared LLLT on chemokine monocyte chemotactic protein-1 (MCP-1) modulation
      in mice. Fifty-two isogenic mice were distributed in seven groups: control (n =
      10, no surgical procedure), laser I (n = 7, surgical procedure and a single LLLT
      exposure 12 h after the surgery), laser II (n = 7, surgery followed by two LLLT
      exposures, 12 and 36 h after surgery), and laser III (n = 7, surgery followed by
      three LLLT exposures, 12, 36, and 60 h after surgery). For each group, a sham
      group (n = 21) underwent surgery without laser application. The animals in the
      laser groups received an infrared diode continuous laser exposure (AsGaAl, 780 nm
      wavelength, power of 20 mW, energy density of 10 J/cm(2), spot size of 0,04
      cm(2)) on three points (20 s per point), and a final energy of 0.4 J. The animals
      were sacrificed 36 h (laser I and sham I groups), 60 h (laser II and sham II),
      and 84 h (laser III and sham III groups) after surgery. The MCP-1 concentrations
      were measured by cytometric bead array. There was no significant difference
      between the three periods in the sham group (p = 0.3). There was a lower
      concentration of MCP-1 in the laser III group compared to the laser I group (p =
      0.05). The infrared LLLT showed a cumulative effect in the modulation of
      chemokine MCP-1 concentration. Three LLLT exposures were necessary to achieve the
      MCP-1 modulation.

PMID- 22415575
TI  - Preparation of 3D fibrin scaffolds for stem cell culture applications.
AB  - Stem cells are found in naturally occurring 3D microenvironments in vivo, which
      are often referred to as the stem cell niche. Culturing stem cells inside of 3D
      biomaterial scaffolds provides a way to accurately mimic these microenvironments,
      providing an advantage over traditional 2D culture methods using polystyrene as
      well as a method for engineering replacement tissues. While 2D tissue culture
      polystrene has been used for the majority of cell culture experiments, 3D
      biomaterial scaffolds can more closely replicate the microenvironments found in
      vivo by enabling more accurate establishment of cell polarity in the environment
      and possessing biochemical and mechanical properties similar to soft tissue. A
      variety of naturally derived and synthetic biomaterial scaffolds have been
      investigated as 3D environments for supporting stem cell growth. While synthetic
      scaffolds can be synthesized to have a greater range of mechanical and chemical
      properties and often have greater reproducibility, natural biomaterials are often
      composed of proteins and polysaccharides found in the extracelluar matrix and as
      a result contain binding sites for cell adhesion and readily support cell
      culture. Fibrin scaffolds, produced by polymerizing the protein fibrinogen
      obtained from plasma, have been widely investigated for a variety of tissue
      engineering applications both in vitro and in vivo. Such scaffolds can be
      modified using a variety of methods to incorporate controlled release systems for
      delivering therapeutic factors. Previous work has shown that such scaffolds can
      be used to successfully culture embryonic stem cells and this scaffold-based
      culture system can be used to screen the effects of various growth factors on the
      differentiation of the stem cells seeded inside. This protocol details the
      process of polymerizing fibrin scaffolds from fibrinogen solutions using the
      enzymatic activity of thrombin. The process takes 2 days to complete, including
      an overnight dialysis step for the fibrinogen solution to remove citrates that
      inhibit polymerization. These detailed methods rely on fibrinogen concentrations
      determined to be optimal for embryonic and induced pluripotent stem cell culture.
      Other groups have further investigated fibrin scaffolds for a wide range of cell
      types and applications - demonstrating the versatility of this approach.

PMID- 22415576
TI  - Entrapped intralesional marrow: a hitherto undescribed imaging feature of benign
      notochordal cell tumour.
AB  - We report two cases of histologically proven benign notochordal cell tumour
      (BNCT) with imaging evidence of entrapped intralesional marrow and discuss the
      relevance of previously undescribed imaging feature.

PMID- 22415577
TI  - Reducing the burden of ischemia reperfusion: editorial to: "Effect of Chronic CPT
      1 Inhibition on Myocardial Ischemia-Reperfusion Injury (I/R) in a Model of Diet
      Induced Obesity" by G. Maarman et al.

PMID- 22415578
TI  - Late effects of chemotherapy and radiotherapy in osteosarcoma and Ewing sarcoma
      patients: the Italian Sarcoma Group Experience (1983-2006).
AB  - BACKGROUND: Patients with osteosarcoma and Ewing sarcoma have achieved longer
      survival over the past decades, but late side effects of chemotherapy and
      radiotherapy have become important concerns. METHODS: The authors reviewed all
      patients with localized osteosarcoma or Ewing sarcoma who had been enrolled in
      the Italian Sarcoma Group neoadjuvant protocols from 1983 through 2006. Data were
      updated in December 2010 to determine 3 endpoints: the incidence of a secondary
      primary cancer (designated as "second malignant neoplasm" [SMN]), infertility,
      and cardiotoxicity. RESULTS: Data were available on 883 patients with
      osteosarcoma and 543 patients with Ewing sarcoma. In the osteosarcoma group,
      there were 39 SMNs (4.4%) in 36 patients; in the Ewing sarcoma group, 15 patients
      (2.8%) experienced a single SMN each. The cumulative 10-year and 20-year
      incidence of an SMN (+/-standard error) was 4.9% +/- 0.9% and 6.1% +/- 1.2%,
      respectively, in the osteosarcoma group and 3.4% +/- 0.9% and 4.7% +/- 1.6%,
      respectively, in the Ewing sarcoma group. The most common SMN in the osteosarcoma
      group was breast cancer (n = 11), and the most common SMN in the Ewing sarcoma
      group was radiotherapy-induced osteosarcoma (n = 6). After 20 years, the risk of
      developing an SMN increased, whereas the risk of a recurrence of the primary
      tumor decreased. Permanent sterility was more common in males than in females.
      Doxorubicin cardiotoxicity occurred in 18 patients with osteosarcoma (2%) and in
      7 patients with Ewing sarcoma (1.3%). CONCLUSIONS: The awareness of late side
      effects in long-term survivors of primary bone cancers should encourage longer
      follow-up.

PMID- 22415580
TI  - Cytotoxicity and cellular impact of dinuclear organoiridium DNA intercalators and
      nucleases with long rigid bridging ligands.
AB  - The DNA binding modes and cleavage properties of novel dinuclear Ir(III)
      polypyridyl (pp) complexes [{(eta(5)-C(5)Me(5))Ir(pp)}(2)(MU-B)](CF(3)SO(3))(4)
      depend on the lengths of their rigid bridging dipyridinyl ligands B. Mono
      intercalation and strong DNA cleavage properties were observed for the
      dipyrido[2,3-a:2',3'-c]phenazine (dppz) complexes 1 (B = 4-[(E)-2-(4
      pyridinyl)ethenyl]pyridine) and 3 (B = 4-(2-pyridin-4-ylethynyl)pyridine), whose
      intracationic Ir...Ir' distances are about 13.1 and 13.3 A, respectively. In
      contrast, UV/Vis and CD spectra were in accordance with a stable intertwined bis
      intercalation mode for pairs of cations of 5 (B = 1,4-di(2-pyridin-4
      ylethynyl)benzene), whose much longer Ir...Ir' distance of 20.6 A allows a stack
      of five aromatic chromophores to be sandwiched between its effectively parallel
      dppz ligands. Whereas both 1 and 3 cleaved DNA in the dark, complex 5 exhibited
      only photoinduced nuclease activity. A significantly higher antiproliferative
      activity towards MCF-7 breast carcinoma cells was observed for the nucleases 1
      and 3, whose IC(50) values of 0.61 and 0.49 were much lower than that of 2.2 MUM
      for bis-intercalator 5. Values of 3.8 MUM, only slightly higher than that of 5,
      were recorded for the 5,6-dimethylphenanthroline complexes 4 and 6, whose
      bridging ligands are identical to those of 3 and 5, respectively. Marked
      antileukemic activity (IC(50) = 6-7 MUM) associated with increased levels of
      reactive oxygen species and apoptosis induction was recorded for both 3 and 5
      towards Jurkat cells at concentrations of 5 MUM and above. Online studies with a
      sensor chip system indicated that 5 MUM solutions of these complexes invoke a
      rapid and massive reduction in MCF-7 cell respiration.

PMID- 22415579
TI  - Hormonal mechanisms for regulation of aggression in human coalitions.
AB  - Coalitions and alliances are core aspects of human behavior. All societies
      recognize alliances among communities, usually based in part on kinship and
      marriage. Aggression between groups is ubiquitous, often deadly, fueled by
      revenge, and can have devastating effects on general human welfare. Given its
      significance, it is surprising how little we know about the neurobiological and
      hormonal mechanisms that underpin human coalitionary behavior. Here we first
      briefly review a model of human coalitionary behavior based on a process of
      runaway social selection. We then present several exploratory analyses of
      neuroendocrine responses to coalitionary social events in a rural Dominican
      community, with the objective of understanding differences between in-group and
      out-group competition in adult and adolescent males. Our analyses indicate: (1)
      adult and adolescent males do not elevate testosterone when they defeat their
      friends, but they do elevate testosterone when they defeat outsiders; (2) pre
      competition testosterone and cortisol levels are negatively associated with
      strength of coalitionary ties; and (3) adult males usually elevate testosterone
      when interacting with adult women who are potential mates, but in a striking
      reversal, they have lower testosterone if the woman is a conjugal partner of a
      close friend. These naturalistic studies hint that reciprocity, dampening of
      aggression, and competition among friends and allies may be biologically embedded
      in unique ways among humans.

PMID- 22415581
TI  - Elimination therapy for the endemic malarias.
AB  - Most malaria diagnosed outside endemic zones occurs in patients experiencing the
      consequences of what was likely a single infectious bite by an anopheline
      mosquito. A single species of parasite is nearly always involved and expert
      opinion on malaria chemotherapy uniformly prescribes species- and stage-specific
      treatments. However the vast majority of people experiencing malaria, those
      resident in endemic zones, do so repeatedly and very often with the involvement
      of two or more species and stages of parasite. Silent forms of these infections
      asymptomatic and beyond the reach of diagnostics-may accumulate to form
      substantial and unchallenged reservoirs of infection. In such settings treating
      only the species and stage of malaria revealed by diagnosis and not others may
      not be sensible or appropriate. Developing therapeutic strategies that address
      all species and stages independently of diagnostic evidence may substantially
      improve the effectiveness of the control and elimination of endemic malaria.

PMID- 22415582
TI  - Are fluoroquinolones superior antibiotics for the treatment of community-acquired
      pneumonia?
AB  - Various guidelines for the antibiotic treatment of community-acquired pneumonia
      (CAP) are presented that include fluoroquinolone antibiotics. The efficacy of
      current fluoroquinolone antibiotics in the treatment of CAP is summarized.
      Healthcare resource utilization and shortened duration of clinical symptoms have
      been shown in some, but not all of CAP trials utilizing fluoroquinolone
      antibiotics. Although evidence for both the clinical and microbiological efficacy
      of fluoroquinolone antibiotics is abundant, no convincing data demonstrates that
      they are superior to other standard antibiotics included in CAP guidelines.

PMID- 22415583
TI  - Increased urinary podocytes following indomethacin suggests drug-induced
      glomerular injury.
AB  - BACKGROUND: Preterm infants are delivered while glomerulogenesis is ongoing and
      may be exposed to insults, including medications that may affect renal
      development. Podocytes detected in the urine are an indicator of glomerular
      injury. The aims of this study were to determine whether preterm and term infants
      excrete podocytes in their urine and whether exposure to gentamicin and
      indomethacin increase podocyte excretion in their urine. METHODS: Preterm infants
      <33 weeks gestation had urine collected each day while receiving either
      gentamicin or indomethacin. Preterm and term control infants had urine collected
      for 3 days. The number of casts and podocytes present in the urine of infants
      receiving indomethacin and gentamicin were compared with preterm and term control
      infants. RESULTS: Forty-two neonates were included in the study. Podocytes were
      present in small numbers (< 2) in the urine of both preterm and term control
      neonates. The number of podocytes in the preterm group receiving indomethacin was
      significantly higher than in all other groups (p=0.02) ,as was urinary albumin
      (p=0.02). CONCLUSIONS: Increased number of podocytes in preterm neonates
      receiving indomethacin and higher excretion of albumin suggest glomerular injury
      is occurring. It is unknown whether injury to glomeruli during glomerulogenesis
      in preterm neonates has long-term sequelae for renal development and function
      into adulthood.

PMID- 22415584
TI  - Boy with autosomal recessive polycystic kidney and autosomal dominant polycystic
      liver disease.
AB  - BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) shows a great
      phenotypic variability between patients, ranging from perinatal demise to mildly
      affected adults. Autosomal dominant polycystic liver disease (PCLD) does not
      manifest in childhood. CASE-DIAGNOSIS/TREATMENT: A boy was reported with the co
      occurrence of ARPKD and PCLD. He presented at the age of 16 days with
      pyelonephritis and urosepsis. Subsequent investigations showed enlarged kidneys
      and hyperechogenic renal medulla and liver parenchyma. Genetic analysis revealed
      compound heterozygous mutations in the PKHD1 gene (p.Arg496X and p.Ser1862Leu).
      After his mother was diagnosed with PCLD, the finding of a liver cyst on
      ultrasound prompted analysis of the PRKCSH gene, revealing a missense mutation
      (p.Arg139His). At the most recent follow-up at 13 years of age, the patient's
      course and clinical examination was uneventful with normal renal and liver
      function without evidence of portal hypertension. CONCLUSIONS: The patient with
      ARPKD and PCLD has so far demonstrated a benign clinical outcome, consistent with
      the great phenotypic variability of ARPKD and, apart from the liver cyst,
      asymptomatic manifestation of PCLD in childhood. However, close long-term follow
      up is mandatory.

PMID- 22415585
TI  - Treatment and outcome of Wilms' tumour patients: an analysis of all cases
      registered in the UKW3 trial.
AB  - BACKGROUND: The randomised findings of the UKW3 trial were that preoperative
      chemotherapy was associated with a more advantageous stage distribution and
      reduction in therapy burden versus immediate nephrectomy without compromising
      outcome in localised Wilms' tumour (WT). We analysed outcome in all WT registered
      in UKW3. PATIENTS AND METHODS: Seven hundred and eighteen WT cases (7%
      anaplastic) were registered in UKW3. We assigned a treatment stage and conducted
      survival analysis. RESULTS: Five-year event-free survival (EFS) and overall
      survival (OS) were 77.2% [95% confidence interval (CI) 73.9-80.2] and 87.5% (95%
      CI 84.8-89.7) after median follow-up of 9.5 years and 10.0 years, respectively.
      Five-year OS in localised non-anaplastic cases was 92.9% (95% CI 90.2-94.9).
      Anaplasia was associated with adverse outcome compared with non-anaplastic cases:
      5-year EFS of 42.0% (95% CI 28.3-55.1) versus 79.8% (95% CI 76.5-82.7) and 5-year
      OS of 60% (95% CI 45.1-72.0) versus 89.6% (95% CI 87.0-91.7), respectively.
      Outcomes were similar for non-anaplastic stage I or II but significantly poorer
      in stage III cases than stage I. Five-year OS after relapse was 54.1% (95% CI
      44.5-62.8). Forty-seven percent of non-anaplastic WT received anthracycline; 27%
      were treated with radiotherapy first line. CONCLUSION: These outcomes provide a
      baseline for future comparisons of WT treatment approach, burden and patient
      outcome.

PMID- 22415587
TI  - Underutilization of genetics services for autism: the importance of parental
      awareness and provider recommendation.
AB  - Reasons for the underutilization of genetics services by families of children
      with autism spectrum disorders (ASD) are not well understood. We report the
      identification of factors associated with this underuse. Survey-based study of
      parents and/or guardians of children with ASD. One hundred fifty-five families
      completed the questionnaire. Thirty-one of 155 (20%) children had seen a genetics
      professional. Forty-nine of 154 (32%) children had undergone genetic testing.
      Parents whose child saw a genetics professional were more likely to 1) Have a
      primary provider refer for or suggest a genetics evaluation 2) Have asked for a
      referral, and/or 3) Know another person with a genetic cause of ASD. amilies of
      children with ASD who have not received genetics services are less aware of their
      availability and utility. They are also less likely to have their provider
      recommend a clinical genetics evaluation. Efforts should be taken to increase
      awareness of both health providers and parents regarding the usefulness of
      genetics services for ASD.

PMID- 22415588
TI  - Aberrant activation of liver X receptors impairs pancreatic beta cell function
      through upregulation of sterol regulatory element-binding protein 1c in mouse
      islets and rodent cell lines.
AB  - AIMS/HYPOTHESIS: Liver X receptors (LXR) are important transcriptional regulators
      of lipid and glucose metabolism. Our previous report demonstrated that LXR
      activation inhibited pancreatic beta cell proliferation through cell cycle
      arrest. Here we explore the role of LXR activation in beta cell insulin secretion
      and the underlying mechanism that might be involved. METHODS: Mouse pancreatic
      islets or insulin-secreting MIN6 cells were exposed to the LXR agonist, T0901317,
      and insulin secretion, glucose and fatty acid oxidation, and lipogenic gene
      expression were assessed. The unsaturated fatty acid eicosapentaenoic acid and
      the dominant negative sterol regulatory element binding protein 1c (SREBP1c) were
      used to inhibit endogenous SREBP1c and evaluate the involvement of SREBP1c in
      beta cell dysfunction induced by LXR activation. RESULTS: Treatment with the LXR
      agonist decreased beta cell glucose sensitivity and impaired glucose-stimulated
      insulin secretion in vivo and in vitro. This was accompanied by derangements of
      beta cell glucose oxygen consumption, glucose oxidation, ATP production and
      intracellular voltage-gated calcium channel flux. LXR activation also regulated
      the expression of lipid metabolism-related genes such as Fas, Acc (also known as
      Acaca) and Cpt1a, and led to intracellular lipid accumulation. Further studies
      revealed that inhibition of SREBP1c abolished LXR activation-induced lipid
      accumulation and improved beta cell glucose metabolism, ATP production and
      insulin secretion. CONCLUSIONS/INTERPRETATION: Our data reveal that aberrant
      activation of LXR reproduced the phenomenon of beta cell dysfunction in the
      development of type 2 diabetes in vitro and in vivo. Upregulation of SREBP1c
      production and the lipotoxicity mediated by it played a central role in this
      process.

PMID- 22415591
TI  - Why voltage-gated Ca2+ and bacterial Na+ channels with the same EEEE motif in
      their selectivity filters confer opposite metal selectivity.
AB  - Voltage-gated sodium (Na(v)) and calcium (Ca(v)) channels, which play essential
      biological roles, are characterized by their ability to discriminate the "native"
      ion from other competing cations. Surprisingly, Na(+)-selective bacterial Na(v)
      and high voltage-activated Ca(2+)-selective Ca(v) channels both exhibit
      selectivity filters (the narrowest part of the open pore) lined by four Glu
      residues that interact specifically with the permeating ions. This raises the
      intriguing question why selectivity filters with the same EEEE motif are Na(+)
      selective in Na(v) channels but Ca(2+)-selective in Ca(v) channels. We show that
      the different degree of metal hydration inside the pore, which is related to the
      pore size and rigidity, can account for the opposite ion selectivity in Na(v) and
      Ca(v) channels with identical EEEE selectivity filters. The results are
      consistent with experimental estimates of the metal hydration structure in Na(v)
      and Ca(v) channels with the EEEE motif. They suggest that the protein matrix,
      which can enhance or attenuate ion-protein interactions relative to ion-solvent
      interactions by controlling the pore's solvent accessibility, size/rigidity, and
      charge state, is a key determinant of Ca(2+)vs. Na(+) selectivity in EEEE
      selectivity filters.

PMID- 22415589
TI  - Pentamethylquercetin generates beneficial effects in monosodium glutamate-induced
      obese mice and C2C12 myotubes by activating AMP-activated protein kinase.
AB  - AIMS/HYPOTHESIS: Pentamethylquercetin (PMQ) has recently been shown to have
      glucose-lowering properties. Here, we aimed to characterise the effectiveness and
      underlying mechanisms of PMQ for ameliorating metabolic disorders in vivo and
      vitro. METHODS: We generated a mouse model of obesity by neonatal administration
      of monosodium glutamate (MSG) and used it to assess the properties of PMQ as a
      treatment for metabolic disorders. We also investigated the possible underlying
      mechanisms of PMQ in the prevention of metabolic disorders. RESULTS: Compared
      with normal mice, MSG mice had metabolic disorders, including central obesity,
      hyperinsulinaemia, insulin resistance, hyperglycaemia, hyperlipidaemia, decreased
      phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase
      (ACC), and downregulated levels of GLUT4 in gastrocnemius muscles. In MSG mice,
      PMQ treatment (5, 10, 20 mg/kg daily) reduced body weight gain, waist
      circumference, adipose tissue mass, serum glucose, triacylglycerol and total
      cholesterol, while improving insulin resistance, activating AMPK and increasing
      ACC phosphorylation and GLUT4 abundance. In C2C12 myotubes, PMQ (10 MUmol/l)
      increased glucose consumption by ~65%. PMQ treatment (1-10 MUmol/l) also
      activated AMPK, increased ACC phosphorylation and GLUT4 abundance, and
      upregulated the expression of some key genes involved in fatty acid oxidation.
      CONCLUSIONS/INTERPRETATION: These findings suggest that PMQ can ameliorate
      metabolic disorders at least in part via stimulation of AMPK activity.

PMID- 22415590
TI  - The effect of inositol hexaphosphate on the expression of selected
      metalloproteinases and their tissue inhibitors in IL-1beta-stimulated colon
      cancer cells.
AB  - INTRODUCTION: Matrix metalloproteinases (MMPs) have repeatedly been shown to play
      a very active role in extracellular matrix degradation associated with tumor
      invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for
      their ability to inhibit MMP activity thereby inhibiting malignant progression.
      Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both
      preventive and therapeutic effects against various cancers including that of
      colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell
      adhesion and migration. In the present study, the effect of IP6 on the expression
      of MMP and TIMP genes was evaluated in unstimulated and IL-1beta-stimulated colon
      cancer cell line Caco-2. MATERIALS AND METHODS: Real-time QRT-PCR was used to
      validate the transcription level of selected MMP and TIMP genes in Caco-2 cells
      after treatment with 1 ng/ml of IL-1beta, 2.5 mM of IP6, and both for 6, 12, and
      24 h. RESULTS: Stimulation of cells with IL-1beta only resulted in an
      overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP
      3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an
      efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription
      stimulated by IL-1beta in 6 h lasting culture. After 12 h, IL-1beta-induced MMP-2
      mRNA expression was significantly reduced by IP6. CONCLUSION: Proinflammatory
      cytokine IL-1beta upregulates MMP and TIMP mRNAs expression in colon cancer
      epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both
      MMP and TIMP genes and downregulates IL-1beta stimulated transcription of some of
      these genes. IP6 exerts its anti-metastatic activity through modulation of MMP
      and TIMP genes expression to prevent cancer cell migration and invasion.

PMID- 22415593
TI  - Diagnostic accuracy of mediastinal width measurement on posteroanterior and
      anteroposterior chest radiographs in the depiction of acute nontraumatic thoracic
      aortic dissection.
AB  - We aimed to explore the diagnostic accuracy of various mediastinal measurements
      in determining acute nontraumatic thoracic aortic dissection with respect to
      posteroanterior (PA) and anteroposterior (AP) chest radiographs, which had
      received little attention so far. We retrospectively reviewed 100 patients (50 PA
      and 50 AP chest radiographs) with confirmed acute thoracic aortic dissection and
      120 patients (60 PA and 60 AP chest radiographs) with confirmed normal aorta.
      Those who had prior history of trauma or aortic disease were excluded. The
      maximal mediastinal width (MW) and maximal left mediastinal width (LMW) were
      measured by two independent radiologists and the mediastinal width ratio (MWR)
      was calculated. Statistical analysis was then performed with independent sample t
      test. PA projection was significantly more accurate than AP projection, achieving
      higher sensitivity and specificity. LMW and MW were the most powerful parameters
      on PA and AP chest radiographs, respectively. The optimal cutoff levels were LMW
      = 4.95 cm (sensitivity, 90 %; specificity, 90 %) and MW = 7.45 cm (sensitivity,
      90 %; specificity, 88.3 %) for PA projection and LMW = 5.45 cm (sensitivity, 76
      %; specificity, 65 %) and MW = 8.65 cm (sensitivity, 72 %; specificity, 80 %) for
      AP projection. MWR was found less useful and less reliable. The use of LMW alone
      in PA film would allow more accurate prediction of aortic dissection. PA chest
      radiograph has a higher diagnostic accuracy when compared with AP chest
      radiograph, with negative PA chest radiograph showing less probability for aortic
      dissection. Lower threshold for proceeding to computed tomography aortogram is
      recommended however, especially in the elderly and patients with widened
      mediastinum on AP chest radiograph.

PMID- 22415595
TI  - Ru-Pt and Ru-Pd heterobimetallic complexes based on a new ligand with two
      distinct chelate sites.
AB  - A new ligand p-[N-2-(2'-pyridyl)benzimidazolyl]-[N-2-(2'-pyridyl)indolyl]-benzene
      (L1) has been synthesized and fully characterized. L1 has two distinct chelating
      sites: one N,N-chelate site and one N,C-chelate site. This ligand has been found
      to be very effective in selective binding to two different metal ions. Two new
      heterobimetallic complexes Ru-Pt and Ru-Pd using L1 as the bridging ligand have
      been successfully synthesized and fully characterized. To understand the mutual
      influence of the two metal centers on electronic and photophysical properties,
      the corresponding monometallic Ru(II), Pt(II) and Pd(II) compounds have also been
      synthesized and investigated. All Ru(II)-containing complexes have been found to
      be luminescent. Electronic communication between the two different metal centers
      in the heterobimetallic compounds was found to be weak. The Pt(II) moiety appears
      to enhance the phosphorescent efficiency of the Ru(II) unit while the Pd(II)
      analogue has little influence.

PMID- 22415594
TI  - Imaging of acute conditions affecting the hepatic vasculature.
AB  - Liver imaging primarily consists of evaluating the parenchyma and biliary system.
      However, the liver has a rich, complex vascularity which can also be affected by
      numerous disease processes. By considering disease processes that primarily
      affect the hepatic veins, portal veins, and hepatic arteries, an anatomy-based
      approach of hepatic vascular diseases can be applied to image interpretation to
      allow rapid diagnosis and prompt initiation of treatment. Computed tomography,
      magnetic resonance imaging, and ultrasound are all effectively used to evaluate
      the liver and can play complimentary roles. In this article, the key imaging
      findings of acute conditions affecting the hepatic veins (passive congestion,
      acute thrombosis/Budd-Chiari, stenosis), portal veins (thrombosis, phlebitis,
      stenosis), hepatic arteries (laceration, pseudoaneurysm, thrombosis), and
      arteriovenous structures (hereditary hemorrhagic telangiectasis, arteriovenous
      fistula) will be reviewed.

PMID- 22415596
TI  - Cytotoxicity of water-soluble mPEG-SH-coated silver nanoparticles in HL-7702
      cells.
AB  - Silver nanoparticles (AgNPs) are being used widely and increasingly in various
      products and medical supplies due to their antibacterial activity. However,
      little is known about the impacts of the AgNPs. Herein, The primary purpose of
      this study was to investigate the cytotoxic effect of AgNPs in the human liver
      cell line (HL-7702). The water-soluble alpha-Methoxy-poly (ethylene glycol)-omega
      mercapto (mPEG-SH)-coated AgNPs (40 nm) were synthesized, which showed superior
      stabilization and uniform dispersion in culture medium. The effect of mPEG-SH
      coated silver nanoparticles on cell viability, leakage of lactate dehydrogenase
      (LDH), oxidative stress, mitochondrial membrane potential (MMP), and cell cycle
      was evaluated after the cells were treated with nanoparticles. The results showed
      that the coated AgNPs could be taken up by cells, decreased cell viability in
      dose- and time-dependent manners at dosage levels between 6.25 and 100.00 MUg/mL,
      caused membrane damage (LDH leakage), and decreased the activities of superoxide
      dismutase and glutathione peroxides. The level of malondialdehyde, an end product
      of lipid peroxidation, was also increased in AgNPs-exposed cells. Moreover, flow
      cytometric analysis showed that AgNP exposure decrease MMP and cause G2/M phase
      arrest. Thus, our data suggest that mPEG-SH-coated AgNPs have the potential
      toxicity that is associated with oxidative stress, apoptosis, and DNA damage.

PMID- 22415597
TI  - Deaths observed in Medicare beneficiaries: average attributable fraction and its
      longitudinal extension for many diseases.
AB  - Calculating the longitudinal extension of the average attributable fraction (LE
      AAF) for many risk factors (RFs) requires a two-stage computational process using
      only those combinations of RFs observed in the dataset. We first screen
      candidates RFs in a Cox Model, and assuming piecewise constant hazards, use
      pooled logistic regression to model the probability of death as a function of
      combinations of selected RFs. We average the iterative differencing of the
      attributable fractions calculated for all overlapping subsets of co-occurring RFs
      to obtain a LE-AAF for each RF that is additive and symmetrical. We illustrate by
      partitioning the additive proportions of death from 10 different groupings of
      acute and chronic diseases, on a national sample of older persons from the US
      (Medicare Beneficiary Survey) over a 4-year period and compare with results
      reported by the National Center for Healthcare Statistics. We conclude that
      careful screening of RFs with analysis restricted to extant combinations greatly
      reduces computational burden. LE-AAF accounted for a cumulative total of 66% of
      the deaths in our sample, compared with the 83% accounted for by the National
      Center for Healthcare Statistics.

PMID- 22415598
TI  - Clinical impact of 18F-choline PET/CT in patients with recurrent prostate cancer.
AB  - PURPOSE: To investigate the clinical value of (18)F-fluorocholine PET/CT (CH
      PET/CT) in treatment decisions in patients with recurrent prostate cancer (rPCA).
      METHODS: The study was a retrospective evaluation of 156 patients with rPCA and
      CH-PET/CT for restaging. Questionnaires for each examination were sent to the
      referring physicians 14-64 months after examination. Questions included
      information regarding initial extent of disease, curative first-line treatment,
      and the treatment plan before and after CH-PET/CT. Additionally, PSA values at
      diagnosis, after initial treatment, before CH-PET/CT and at the end of follow-up
      were also obtained from the questionnaires. RESULTS: Mean follow-up was 42
      months. The mean Gleason score was 6.9 at initial diagnosis. Initial treatment
      was: radical prostatectomy in 110 patients, radiotherapy in 39, and combined
      prostatectomy and radiotherapy in 7. Median PSA values before CH-PET/CT and at
      the end of follow-up were 3.40 ng/ml and 0.91 ng/ml. PSA levels remained stable,
      decreased or were below measurable levels in 108 patients. PSA levels increased
      in 48 patients. In 75 of the 156 patients (48%) the treatment plan was changed
      due to the CH-PET/CT findings. In 33 patients the therapeutic plan was changed
      from palliative treatment to treatment with curative intent. In 15 patients
      treatment was changed from curative to palliative. In 8 patients treatment was
      changed from curative to another strategy and in 2 patients from one palliative
      strategy to another. In 17 patients the treatment plan was adapted. CONCLUSION:
      CH-PET/CT has an important impact on the therapeutic strategy in patients with
      rPCA and can help to determine an appropriate treatment.

PMID- 22415600
TI  - The importance of standardized interpretation of molecular breast imaging with
      dedicated gamma cameras.

PMID- 22415599
TI  - Relationship between late ventricular potentials and myocardial 123I
      metaiodobenzylguanidine scintigraphy in patients with dilated cardiomyopathy with
      mild to moderate heart failure: results of a prospective study of sudden death
      events.
AB  - PURPOSE: Late ventricular potentials (LPs) are considered to be useful for
      identifying patients with heart failure at risk of developing ventricular
      arrhythmias. (123)I-metaiodobenzylguanidine (MIBG) scintigraphy, which is used to
      evaluate cardiac sympathetic activity, has demonstrated cardiac sympathetic
      denervation in patients with malignant ventricular tachyarrhythmias. This study
      was undertaken to clarify the relationship between LPs and (123)I-MIBG
      scintigraphy findings in patients with dilated cardiomyopathy (DCM). METHODS: A
      total of 56 patients with DCM were divided into an LP-positive group (n = 24) and
      an LP-negative group (n = 32). During the compensated period, the delayed
      heart/mediastinum count (H/M) ratio, delayed total defect score (TDS), and
      washout rate (WR) were determined from (123)I-MIBG images and plasma brain
      natriuretic peptide (BNP) concentrations were measured. Left ventricular end
      diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left
      ventricular ejection fraction (LVEF) were simultaneously determined by
      echocardiography. RESULTS: LVEDV, LVESV, LVEF and plasma BNP concentrations were
      similar in the two groups. However, TDS was significantly higher (35 +/- 8 vs. 28
      +/- 6, p < 0.005), the H/M ratio was significantly lower (1.57 +/- 0.23 vs. 1.78
      +/- 0.20, p < 0.005), and the WR was significantly higher (60 +/- 14% vs. 46 +/-
      12%, p < 0.001) in the LP-positive than in the LP-negative group. The average
      follow-up time was 4.5 years, and there were nine sudden deaths among the 56
      patients (16.1%). In logistic regression analysis, the incidences of sudden death
      events were similar in those LP-negative with WR <50%, LP-negative with WR >= 50%
      and LP-positive with WR <50% (0%, 10.0% and 14.3%, respectively), but was
      significantly higher (41.2%) in those LP-positive with WR >= 50% (p < 0.01, p <
      0.05, and p < 0.05, respectively). CONCLUSION: The present study demonstrated
      that the values of cardiac (123)I-MIBG scintigraphic parameters were worse in LP
      positive DCM patients than in LP-negative DCM patients. Furthermore, in LP
      positive DCM patients with a high WR, the incidence of sudden death events was
      higher than that in other subgroups of DCM patients.

PMID- 22415601
TI  - Slow down to stay alive: HER4 protects against cellular stress and confers
      chemoresistance in neuroblastoma.
AB  - BACKGROUND: Neuroblastoma (NBL) is a common pediatric solid tumor, and outcomes
      for patients with advanced neuroblastoma remain poor despite extremely aggressive
      treatment. Chemotherapy resistance at relapse contributes heavily to treatment
      failure. The poor survival of patients with high-risk NBL prompted this
      investigation into novel treatment options with the objective of gaining a better
      understanding of resistance mechanisms. On the basis of previous work and on data
      from publicly available studies, the authors hypothesized that human epidermal
      growth factor receptor 4 (Her4) contributes to resistance. METHODS: Her4
      expression was reduced with small-hairpin RNA (shRNA) to over express
      intracellular HER4, and the authors tested its impact on tumor cell survival
      under various culture conditions. The resulting changes in gene expression after
      HER4 knockdown were measured by using a messenger RNA (mRNA) array. RESULTS: HER4
      expression was up-regulated in tumor spheres compared with the expression in
      monolayer culture. With HER4 knockdown, NBL cells became less resistant to
      anoikis and serum starvation. Moreover, HER4 knockdown increased the
      chemosensitivity of NBL cells to cisplatin, doxorubicin, etoposide, and activated
      ifosfamide. In mRNA array analysis, HER4 knockdown predominately altered genes
      related to cell cycle regulation. In NBL spheres compared with monolayers, cell
      proliferation was decreased, and cyclin D expression was reduced. HER4 knockdown
      reversed cyclin D suppression. Overexpressed intracellular HER4 slowed the cell
      cycle and induced chemoresistance. CONCLUSIONS: The current results indicated
      that HER4 protects NBL cells from multiple exogenous apoptotic stimuli, including
      anoikis, nutrient deficiency, and cytotoxic chemotherapy. The intracellular
      fragment of HER4 was sufficient to confer this phenotype. HER4 functions as a
      cell cycle suppressor, maintaining resistance to cellular stress. The current
      findings indicate that HER4 overexpression may be associated with refractory
      disease, and HER4 may be an important therapeutic target.

PMID- 22415602
TI  - Comparing current definitions of return to work: a measurement approach.
AB  - INTRODUCTION: Return-to-work (RTW) status is an often used outcome in work and
      health research. In low back pain, work is regarded as a normal activity a worker
      should return to in order to fully recover. Comparing outcomes across studies and
      even jurisdictions using different definitions of RTW can be challenging for
      readers in general and when performing a systematic review in particular. In this
      study, the measurement properties of previously defined RTW outcomes were
      examined with data from two studies from two countries. METHODS: Data on RTW in
      low back pain (LBP) from the Canadian Early Claimant Cohort (ECC); a workers'
      compensation based study, and the Dutch Amsterdam Sherbrooke Evaluation (ASE)
      study were analyzed. Correlations between outcomes, differences in predictive
      validity when using different outcomes and construct validity when comparing
      outcomes to a functional status outcome were analyzed. RESULTS: In the ECC all
      definitions were highly correlated and performed similarly in predictive
      validity. When compared to functional status, RTW definitions in the ECC study
      performed fair to good on all time points. In the ASE study all definitions were
      highly correlated and performed similarly in predictive validity. The RTW
      definitions, however, failed to compare or compared poorly with functional
      status. Only one definition compared fairly on one time point. CONCLUSIONS:
      Differently defined outcomes are highly correlated, give similar results in
      prediction, but seem to differ in construct validity when compared to functional
      status depending on societal context or possibly birth cohort. Comparison of
      studies using different RTW definitions appears valid as long as RTW status is
      not considered as a measure of functional status.

PMID- 22415603
TI  - Near-UV laser treatment of extrinsic dental enamel stains.
AB  - BACKGROUND AND OBJECTIVES: The selective ablation of extrinsic dental enamel
      stains using a 400-nm laser is evaluated at several fluences for completely
      removing stains with minimal damage to the underlying enamel. STUDY
      DESIGN/MATERIALS AND METHODS: A frequency-doubled Ti:sapphire laser (400-nm
      wavelength, 60-nanosecond pulse duration, 10-Hz repetition rate) was used to
      treat 10 extracted human teeth with extrinsic enamel staining. Each tooth was
      irradiated perpendicular to the surface in a back-and-forth motion over a 1-mm
      length using an ~300-um-diam 10th-order super-Gaussian beam with fluences ranging
      from 0.8 to 6.4 J/cm(2) . Laser triangulation determined stain depth and volume
      removed by measuring 3D surface images before and after irradiation. Scanning
      electron microscopy evaluated the surface roughness of enamel following stain
      removal. Fluorescence spectroscopy measured spectra of unbleached and
      photobleached stains in the spectral range of 600-800 nm. RESULTS: Extrinsic
      enamel stains are removed with laser fluences between 0.8 and 6.4 J/cm(2) .
      Stains removed on sound enamel leave behind a smooth enamel surface. Stain
      removal in areas with signs of earlier cariogenic acid attacks resulted in
      isolated and randomly located laser-induced, 50-um-diam enamel pits. These pits
      contain 0.5-um diam, smooth craters indicative of heat transfer from the stain to
      the enamel and subsequent melting and water droplet ejection. Ablation stalling
      of enamel stains is typically observed at low fluences (<3 J/cm(2) ) and is
      accompanied by a drastic reduction in porphyrin fluorescence from the Soret band.
      CONCLUSION: Laser ablation of extrinsic enamel stains at 400 nm is observed to be
      most efficient above 3 J/cm(2) with minimal damage to the underlying enamel.
      Unsound underlying enamel is also observed to be selectively removed after
      irradiation.

PMID- 22415604
TI  - Reduced visual discrimination in cochlear implant users.
AB  - The aim of the study was to investigate low-level visual function in cochlear
      implant users. Spatial frequency discrimination was assessed in 16 adults with
      normal hearing and 18 adults with profound deafness who had a cochlear implant.
      Thresholds were measured with sinusoidal gratings using a two-alternative
      temporal forced-choice procedure combined with an adaptive staircase. Cochlear
      implant users had significantly poorer spatial frequency discrimination compared
      with normal hearing participants. Therefore, auditory privation leads to
      substantial changes in this particular visual function and these changes remain
      even after the restoration of hearing with a cochlear implant.

PMID- 22415605
TI  - 5-HT1A and 5-HT7 receptors contribute to lurasidone-induced dopamine efflux.
AB  - Lurasidone is a novel, atypical antipsychotic drug with serotonin [5
      hydroxytryptamine (5-HT)]2A, 5-HT7, dopamine (DA) D2 antagonist, and 5-HT1A
      receptor partial agonist properties. The ability of lurasidone to reverse the
      effects of subchronic administration phencyclidine, to impair novel object
      recognition in rats, an animal model of cognitive impairment in schizophrenia, is
      dependent, in part, on its 5-HT1A agonist and 5-HT7 receptor antagonist
      properties. We tested whether 5-HT1A partial agonism or 5-HT7 antagonism, or
      both, contributed to the ability of lurasidone to enhance cortical and
      hippocampal DA efflux, which may be related to its ability to improve cognition.
      Here, we report that lurasidone, 0.25 and 0.5, but not 0.1 mg/kg, subcutaneously,
      significantly increased DA efflux in the prefrontal cortex and hippocampus in a
      dose-dependent manner. Lurasidone, 0.5 mg/kg, also produced a smaller increase in
      DA efflux in the nucleus accumbens. Pretreatment with the 5-HT1A receptor
      antagonist, WAY100635 (0.2 mg/kg, subcutaneously), partially blocked the
      lurasidone-induced cortical and hippocampal DA efflux. Further, subeffective
      doses of the 5-HT1A receptor agonist, tandospirone (0.2 mg/kg), or the 5-HT7
      antagonist, SB269970 (0.3 mg/kg), potentiated the ability of a subeffective dose
      of lurasidone (0.1 mg/kg) to increase DA efflux in the prefrontal cortex. These
      findings suggest that the effects of lurasidone on the prefrontal cortex and
      hippocampus, DA efflux are dependent, at least partially, on its 5-HT1A agonist
      and 5-HT7 antagonist properties and may contribute to its efficacy to reverse the
      effects of subchronic phencyclidine treatment and improve schizophrenia.

PMID- 22415606
TI  - Economic factors in of patients' nonadherence to antidepressant treatment.
AB  - PURPOSE: Patients' nonadherence to antidepressant treatment hampers cost and
      efficacy of depression-specific treatment. However, previous studies have failed
      to find consistent findings in economic effect on nonadherence and also failed to
      reach consensus in how to measure nonadherence to treatment. The study attempts
      to investigate income effect on nonadherence to selective serotonin reuptake
      inhibitors (SSRIs) treatment with clear definitions of nonadherence: self
      discontinuation of SSRIs (nonpersistence) and under-dose of SSRIs
      (noncompliance). METHODS: The study extracted data from the National Comorbidity
      Survey-Replication (NCS-R). The study sample (n = 280) includes adults between
      the ages of 18 and 64 who were diagnosed with Diagnostic Statistics Manual IV
      Major Depressive Episode (MDE) at some point during their lifetime and medicated
      with SSRIs in the past 12 months. RESULTS: Just above poverty level of family
      income and no health insurance increased the risk of medication nonpersistence in
      SSRIs treatment. The study findings confirmed that African Americans were at
      higher risk of medication noncompliance than Whites (odds ratio, 4.53) and MDE
      comorbidity was positively associated with medication noncompliance (odds ratio,
      4.25). CONCLUSIONS: Low income level, combined with health insurance status, and
      race/ethnicity, predict nonadherence to antidepressant treatment. The study
      findings would help physicians and hospitals developing interventional strategies
      and programs to increase patients' adherence rates in antidepressant treatment.

PMID- 22415608
TI  - Participation in cancer rehabilitation and unmet needs: a population-based cohort
      study.
AB  - PURPOSE: To investigate associations between cancer survivors' sex, age, and
      diagnosis in relation to their (1) need for rehabilitation, (2) participation in
      rehabilitation activities, and (3) unmet needs for rehabilitation in a 14-month
      period following date of diagnosis. METHODS: A population-based cohort study was
      performed on incident cancer patients diagnosed from 1 October 2007 to 30
      September 2008. Fourteen months after diagnosis, participants completed a
      questionnaire developed to measure the aspects of rehabilitation. Logistic
      regression analyses were used to explore the association between sex, age, and
      diagnosis, and the outcome variables for rehabilitation. RESULTS: A total of
      3,439 patients participated, yielding an overall response rate of 70%. One third
      of the cancer patients reported a need for physical rehabilitation and one third
      for psychological rehabilitation. Half of the patients participated in at least
      one activity. Unmet needs were most often reported in psychological, sexual, and
      financial areas. Women expressed more needs, participated more often in
      rehabilitation activities, and had, to a higher extent, their emotional needs
      fulfilled. Breast cancer patients participated more often in physical
      rehabilitation. Elderly who expressed rehabilitation needs more often had them
      unresolved. CONCLUSIONS: A substantial variation in rehabilitation needs,
      participation in activities, and unmet needs in relation to sex, age, and cancer
      type was observed. Cancer care ought to systematically address the wide range of
      needs in all groups through integration of systematic needs assessment and
      targeted supply of offers.

PMID- 22415607
TI  - Effect of gamma radiation on bonding to human enamel and dentin.
AB  - PURPOSES: This study evaluated the effect of gamma radiation on the microtensile
      bond strength of resin-based composite restoration to human enamel and dentin
      performed either before or after radiotherapy. METHODS: Thirty sound human third
      molars were sectioned mesio-distally into buccal and lingual halves and then
      randomly divided into enamel or dentin groups. Enamel and dentin substrates were
      randomly divided into three sub-groups (n = 10): Control, which received no
      irradiation; specimens were irradiated before restoration protocol; and specimens
      were irradiated after restoration protocol. Radiation therapy was defined by
      application of 60-Gy dose fractionally with daily exposures of 2 Gy, 5 days a
      week, over 6 weeks. Restorations were carried out using Adper Single Bond
      adhesive system and Filtek Z250 resin composite. The specimens were sectioned
      producing 4 sticks per specimen and submitted to microtensile on a testing
      machine. Data were submitted to two-way ANOVA followed by Tukey test (p < 0.05).
      Failure modes were examined under optical microscopy and SEM. RESULTS: Bond
      strength to enamel was significantly higher than to dentin irrespective radiation
      therapy. Radiotherapy applied before restoration significantly reduced the bond
      strength to both substrates. A predominance of adhesive failures was detected for
      control groups and groups restored before radiotherapy. Cohesive failures in
      dentin and enamel increased when the specimens were restored after irradiation.
      CONCLUSIONS: The gamma radiation had a significant detrimental effect on bond
      strength to human enamel and dentin when the adhesive restorative procedure was
      carried out after radiotherapy.

PMID- 22415609
TI  - Factors related to use of the Internet as a source of health information by
      urological cancer patients.
AB  - AIMS: The aims of this study were to describe the profile of urological cancer
      patients who look for health information on the Internet and to analyse the
      factors related to use of the Internet as a source of health information.
      METHODOLOGY: A cross-sectional descriptive study using individual, semi
      structured, questionnaire-based interviews was carried out in oncology clinics in
      a hospital in Granada (Spain) in a sample group of 169 patients with prostate,
      bladder and kidney cancer. The dependent variable was use of the Internet as a
      source of health information. The independent variables were sociodemographic
      variables, health status, relationship with healthcare services, patient's role
      in decision-making process, satisfaction with healthcare, Internet use, Internet
      skills and attitude. Data analyses include descriptive, bivariate and
      multivariate analyses. RESULTS: Of the patients in the sample group, 72.2 % had
      prostate cancer, 19.4 % had bladder cancer and 8.3 % had kidney cancer. Only 11.2
      % of patients in the group used the Internet as a source of health information.
      These patients were typically men of an average age of 62 years, who live in
      urban areas, who have completed secondary or university education, with a high
      income and who usually share the role of decision maker with their doctor.
      Patients who use the Internet as a source of health information usually look for
      support from psychological support groups, have family members who also look for
      information on the Internet and prefer sources of information other than those
      provided by the health services. CONCLUSIONS: The study outlines the profile of
      urological cancer patients who use the Internet as a source of health
      information. Internet use is related to a patient's attitude towards decision
      making, level of education and whether or not they look for information from
      sources other than the health system itself.

PMID- 22415610
TI  - Drug-induced hallucinatory syndrome in a patient with breast cancer after
      paclitaxel infusion.

PMID- 22415611
TI  - Aligned carbon nanotube, graphene and graphite oxide thin films via substrate
      directed rapid interfacial deposition.
AB  - A procedure for depositing thin films of carbon nanostructures is described that
      overcomes the limitations typically associated with solution based methods.
      Transparent and conductively continuous carbon coatings can be grown on virtually
      any type of substrate within seconds. Interfacial surface tension gradients
      result in directional fluid flow and film spreading at the water/oil interface.
      Transparent films of carbon nanostructures are produced including aligned ropes
      of single-walled carbon nanotubes and assemblies of single sheets of chemically
      converted graphene and graphite oxide. Process scale-up, layer-by-layer
      deposition, and a simple method for coating non-activated hydrophobic surfaces
      are demonstrated.

PMID- 22415613
TI  - Ligand binding assays in the 21st century laboratory: recommendations for
      characterization and supply of critical reagents.
AB  - Critical reagents are essential components of ligand binding assays (LBAs) and
      are utilized throughout the process of drug discovery, development, and post
      marketing monitoring. Successful lifecycle management of LBA critical reagents
      minimizes assay performance problems caused by declining reagent activity and can
      mitigate the risk of delays during preclinical and clinical studies. Proactive
      reagent management assures adequate supply. It also assures that the quality of
      critical reagents is appropriate and consistent for the intended LBA use
      throughout all stages of the drug development process. This manuscript summarizes
      the key considerations for the generation, production, characterization,
      qualification, documentation, and management of critical reagents in LBAs, with
      recommendations for antibodies (monoclonal and polyclonal), engineered proteins,
      peptides, and their conjugates. Recommendations are given for each reagent type
      on basic and optional characterization profiles, expiration dates and storage
      temperatures, and investment in a knowledge database system. These
      recommendations represent a consensus among the authors and should be used to
      assist bioanalytical laboratories in the implementation of a best practices
      program for critical reagent life cycle management.

PMID- 22415612
TI  - Challenges in development of targeted liposomal therapeutics.
AB  - Liposomes, phospholipid vesicles with a bilayered membrane structure, have been
      widely used as pharmaceutical carriers for drugs and genes, in particular for
      treatment of cancer. To enhance the efficacy of the liposomal drugs, drug-loaded
      liposomes are targeted to the tumors by means of passive (enhanced permeability
      and retention mediated) targeting, based on the longevity of liposomes in blood
      and its accumulation in pathological sites with compromised vasculature, and
      active targeting, based on the attachment of specific ligands to the liposomal
      surface to bind certain antigens on the target cells. Antibody-targeted liposomes
      loaded with anticancer drugs demonstrate high potential for clinical
      applications. This review highlights evolution of liposomes for both passive and
      active targeting and challenges in development of targeted liposomal therapeutics
      specifically antibody-targeted liposomes.

PMID- 22415614
TI  - Role of metabolism in the effects of genistein and its phase II conjugates on the
      growth of human breast cell lines.
AB  - Genistein has been investigated for several decades for its potential role in
      breast cancer prevention. Previous researches have shown that glucuronide and
      sulfate conjugates are the major species circulating in the blood after genistein
      ingestion. It was hypothesized that enzymes (UDP-glucuronosyltransferases,
      sulphotransferases, beta-glucuronidases, and sulphatases) present in breast
      tissues would catalyze the inter-conversion between the aglycone and the
      conjugates in situ. Therefore, our aim was to investigate how genistein,
      genistein-7-glucuronide (G-7-G), genistein-7-sulfate (G-7-S), and 4'-sulfate (G
      4'-S) were metabolized in mammary cells and to determine the effects of
      metabolism on their proliferative actions using cultured breast cell lines. As
      expected, genistein stimulated the cell growth of breast cancer cells (MCF-7 and
      T47D) concentration-dependently at lower concentrations but inhibited their
      growth at higher concentration. It showed low activities in a non-tumorigenic
      cell line (MCF-10A) due to the absence of ERalpha. Genistein was extensively
      metabolized to glucuronides by MCF-7 and to sulfates by T47D, while it was poorly
      metabolized by MCF-10A. G-7-G displayed weak stimulation activity in breast
      cancer cells. G-7-G underwent extensive metabolism in T47D and MCF-10A but not in
      MCF-7. The proliferative effects of G-7-G on MCF-7 and T47D were associated with
      its hydrolysis to genistein in these cells. In contrast, G-7-S and G-4'-S were
      not metabolized by these three cells and had no effects on their growth. In
      conclusion, production of phase II metabolites did not affect the proliferation
      effect of genistein on MCF-7 and T47D. Deconjugation was correlated to the
      apparent proliferative effects of G-7-G in breast cancer cells.

PMID- 22415615
TI  - Complex [corrected] regional pain syndrome: what specialized rehabilitation
      services do patients require?
AB  - Complex [corrected] regional pain syndrome (CRPS) is a complex disorder, the
      optimal treatment of which requires an interdisciplinary approach encompassing
      medical, interventional, psychological, and rehabilitation services that
      emphasize the role of physical and occupational therapies. The central focus of
      treatment is the restoration of function, utilizing a systematic, coordinated,
      and progressive set of therapeutic strategies. The poorly delineated
      pathophysiology and variable course of CRPS suggest that individualized
      strategies are required for optimal management, but also mean that carefully
      controlled trials of physiotherapy are difficult to conduct. This article
      presents a brief review of the nature and pathophysiology of CRPS, the medical
      and psychological approaches that have been found to be effective, and a review
      of the current trends in rehabilitation.

PMID- 22415616
TI  - The inverted CD4/CD8 ratio and associated parameters in 66-year-old individuals:
      the Swedish HEXA immune study.
AB  - The Swedish OCTO and NONA immune longitudinal studies were able to identify and
      confirm an immune risk profile (IRP) predictive of an increased 2-year mortality
      in very old individuals, 86-94 years of age. The IRP, was associated with
      persistent cytomegalovirus infection and characterized by inverted CD4/CD8 ratio
      and related to expansion of terminally differentiated effector memory T cells
      (TEMRA phenotype). In the present HEXA immune longitudinal study, we have
      examined a younger group of elderly individuals (n = 424, 66 years of age) in a
      population-based sample in the community of Jonkoping, Sweden, to examine the
      relevance of findings previously demonstrated in the very old. Immunological
      monitoring that was conducted included T cell subsets and CMV-IgG and CMV-IgM
      serology. The result showed a prevalence of 15 % of individuals with an inverted
      CD4/CD8 ratio, which was associated with seropositivity to cytomegalovirus and
      increases in the level of TEMRA cells. The proportion of individuals with an
      inverted CD4/CD8 ratio was significantly higher in men whereas the numbers of
      CD3+CD4+ cells were significantly higher in women. In conclusion, these findings
      are very similar to those previously found by us in the Swedish longitudinal
      studies, suggesting that an immune profile previously identified in the very old
      also exists in the present sample of hexagenerians. Therefore, it will be
      important to examine clinical parameters, including morbidity and mortality, to
      assess whether the immune profile also is a risk profile associated with higher
      mortality in this sample of hexagenerians.

PMID- 22415617
TI  - [Pneumology in Germany: from basic research to patient care].

PMID- 22415618
TI  - [Acceptance of a telemonitoring device in patients  with chronic obstructive
      pulmonary disease].
AB  - OBJECTIVE: The aim of this trial was to assess the acceptance of a telemonitoring
      device (Health Buddy(r)) by patients with chronic obstructive pulmonary disease
      (COPD). The device makes it possible to monitor vital parameters and to ask
      questions about symptoms, behavior and disease-specific knowledge. METHOD: A
      single-arm non-randomized clinical study was performed for three months in 43
      patients with severe/very severe COPD. The primary intent was to determine the
      patients' compliance with the device. In addition the patients were questioned
      about their general acceptance of the telemonitoring intervention, their quality
      of life and the overall use of resources. RESULTS: 36 patients (25 men, 11 women,
      mean age 67,9 +/- 6,9; range 54 - 81 years) completed the protocol. All 43
      patients were using the device (Health Buddy(r)) on two thirds of all possible
      working days (this had been predefined as full compliance). Especially the
      questions on technical functioning of the device, trust in the technique and data
      security, as well as the confidentiality of communication with the physician via
      telemedicine were very positively answered. Health-related quality of life did
      not change and no rise of autonomy was noted. However, the objective of early
      detecting of acute exacerbations by daily measurements of vital parameters and
      assessment of symptoms was difficult to achieve because of inadequate definition
      of the parameters. CONCLUSION: This cohort of patients with advanced COPD was
      highly compliant in the use of the telemonitoring device. But clinical efficacy
      and economic effectiveness remain to be investigated.

PMID- 22415619
TI  - [Dyspnoea after complication-free tracheostomy].
AB  - HISTORY: A 70-year-old woman had been under oncological supervision for several
      years because of breast cancer with bone and lymph node metastases. For several
      weeks she had been treated for increasing vocal cord paresis of uncertain cause,
      requiring a tracheostomy, a speech cannula being inserted after eight days.
      Several days later the patient began to complain of dyspnea, but repeated
      inspection and cleaning of the cannula failed to reveal its cause. The
      increasingly anxious patient was given a benzodiazepine preparation to calm her.
      She was then transferred to the intensive care unit because of worsening
      respiratory insufficiency and impaired consciousness. DIAGNOSIS AND COURSE: A
      fiberoptic bronchoscopy was performed immediately, which revealed a black foreign
      body immediately distal to the tip of the tracheal cannula. The cannula was
      removed and the slightly sedated patient at once coughed up a large amount of
      bronchial secretion and a long, curved and fairly firm blood clot. Control
      bronchoscopy now revealed a flat, slightly hemorrhagic ulcer on the dorsal
      tracheal wall at the point where the cannula tip had made contact with the
      tracheal wall. CONCLUSION: Even trained personnel may have difficulty in
      recognizing intratracheal thrombi in patients with a tracheostomy. It is thus
      essential that an endoscopy is performed in patients with obstructive symptoms
      after a tracheostomy.

PMID- 22415620
TI  - [44-year-old man from Southeast Asia with chest pain].

PMID- 22415621
TI  - [Difficult and severe asthma in adults: definition, diagnosis and treatment].

PMID- 22415622
TI  - [Should we always use EGFR mutation analysis prior to palliative firstline
      therapy of metastatic adenocarcinoma of the lung? Pro].

PMID- 22415623
TI  - [Should we always use EGFR mutation analysis prior to palliative firstline
      therapy of metastatic adenocarcinoma of the lung? Contra].

PMID- 22415624
TI  - [Idiopathic pulmonary fibrosis: modern guideline-concordant diagnostics and
      innovative treatment].
AB  - Interstitial lung diseases are a heterogenic group of diseases who share in
      common manifestation of the disease process in the distal airways and alevolo
      capilary membrane. Idiopathic pulmonary fibrosis (IPF) is of special interest as
      it is the most prevalent entity within the idiopathic interstitial pneumonias and
      it is associated with the worst prognosis. Diagnosis of IPF necessitates
      confirmation of a "usual interstitial pneumonia" (UIP) pattern on high-resolution
      computed tomography or on histology from a surgical lung biopsy. The recently
      published evidence-based IPF-guidelines for the first time define radiologic
      criteria for a UIP pattern and thus allow to make an IPF diagnosis in the absence
      of a surgical lung biopsy. Moreover, an IPF diagnosis can be made only after
      exclusion of any other cause for an interstitial lung disease.In the new IPF
      guideline no medical therapy has received a positive recommendation. Based on the
      available evidence only pirfenidone has been shown to attenuate disease
      progression in mild to moderate IPF populations, with low-moderate quality of
      evidence. Pirfenidone has been approved for mild-moderate IPF in the European
      Union in February 2011 and is approved in Japan since 2009. In IPF-patients who
      cannot receive pirfenidone high-dose N-acetylcysteine is an "off-label-use"
      option that also has been shown to slow disease progression, however, based on
      low quality of evidence only. Recent studies suggest that anti-inflammatory
      therapies (prednione, azathioprine) may be harmful in IPF patients and cannot be
      recommended. Besides medical therapies IPF patients should receive best
      supportive care, which includes long-term oxygen therapy in hypoxemic patients
      and pulmonary rehabilitation as well as lung transplantation for eligible
      patients.

PMID- 22415625
TI  - [Gout as a systemic disease. Manifestations, complications and comorbidities of
      hyperuricaemia].
AB  - Of all inflammatory rheumatic diseases gout has the highest prevalence. Patients
      with intermittent acute gout attacks are usually treated by primary care
      physicians. However, in cases of insufficient long-term control of serum uric
      acid levels, complications or atypical clinical manifestations may necessitate
      consultation with a rheumatologist in the further course of the disease. An
      oligoarticular or polyarticular presentation can give rise to the initial
      suspicion of rheumatoid or psoriatic arthritis. In these cases a careful clinical
      work-up supported by laboratory and imaging investigations is necessary and
      synovial fluid analysis is usually required. As in other rheumatic diseases extra
      articular manifestations are of utmost importance for morbidity and mortality.
      Gout is a complex metabolic and inflammatory disease and besides articular
      symptoms the renal and cardiovascular effects of hyperuricemia are particularly
      relevant for the overall prognosis.

PMID- 22415626
TI  - Urinary incontinence: prevalence, risk factors, and impact on health related
      quality of life in Saudi women.
AB  - AIMS: The aims of this study were to determine the prevalence, risk factors, and
      impact upon health related quality of life (HRQL) of urinary incontinence in
      Saudi women. METHODS: We performed a clinic-based cross-sectional survey. 6,600
      women aged 20 years and older were selected. The bother of urinary incontinence
      symptoms was assessed using the Arabic version of the short form of Urogenital
      Distress Inventory (UDI-6) questionnaire. We measured the impact of urinary
      incontinence on HRQL using the Incontinence Impact Questionnaire (IIQ-7).
      RESULTS: The overall prevalence of urinary incontinence in our study was 29%. The
      prevalence of urinary incontinence according to its type was 50% stress urinary
      incontinence, 28% urgency urinary incontinence, and 22% mixed urinary
      incontinence. Older age, obesity, large baby birth weight, high parity, caesarean
      delivery, vaginal delivery, and diabetes were significant risk factors. Less than
      10% of the women in this study reported a significant effect of urinary
      incontinence on their HRQL. In our study population, 9% sought medical care.
      CONCLUSIONS: Twenty-nine percent of the women in Riyadh suffered from urinary
      incontinence. Diabetes is the most significant factor. Urinary incontinence
      affects women's HRQL. Most of the women did not seek medical care. We consider
      our study as an important step to start the plans for early detection, and
      treating urinary incontinence in Saudi Arabia.

PMID- 22415627
TI  - Posterior pelvic floor disorders and obstructed defecation syndrome: clinical and
      therapeutic approach.
AB  - There are no clear recommended imaging guidelines for the assessment of patients
      presenting primarily with obstructed defecation syndrome and defecation
      difficulty. The gold standard has always been the defecating proctogram which may
      require a rather poorly tolerated extended technique involving high-radiation
      exposure in young women which includes cystography, vaginography, small bowel
      opacification, and occasional peritoneography. The development of dynamic
      magnetic resonance imaging has obviated many of these extended techniques and may
      be supplemented by novel ultrasonographic methods including dynamic transperineal
      sonography, real-time 3D translabial ultrasound and 3D dynamic echodefecography.
      Patients potentially suitable for surgical treatment display a multiplicity of
      pelvic floor and perineal soft-tissue anomalies where one pathology (such as
      rectocele or enterocele) are considered dominant. Despite the introduction of
      recent stapled and robotic technologies, there is a dual dialog concerning the
      functional outcome of these procedures. Imaging and surgical algorithms for these
      patients are provided. 

PMID- 22415629
TI  - Modular synthesis of optically active lactones by Ru-catalyzed asymmetric allylic
      carboxylation and ring-closing metathesis reaction.
AB  - A new synthetic route to optically active unsaturated gamma- and delta-lactones
      has been demonstrated via asymmetric allylic carboxylation with a planar-chiral
      Cp'Ru catalyst and ring-closing metathesis reaction with a Grubbs II catalyst,
      and successfully applied to the enantioselective synthesis of (R)-(-)
      massoialactone.

PMID- 22415630
TI  - Likelihood-based methods for regression analysis with binary exposure status
      assessed by pooling.
AB  - The need for resource-intensive laboratory assays to assess exposures in many
      epidemiologic studies provides ample motivation to consider study designs that
      incorporate pooled samples. In this paper, we consider the case in which
      specimens are combined for the purpose of determining the presence or absence of
      a pool-wise exposure, in lieu of assessing the actual binary exposure status for
      each member of the pool. We presume a primary logistic regression model for an
      observed binary outcome, together with a secondary regression model for exposure.
      We facilitate maximum likelihood analysis by complete enumeration of the possible
      implications of a positive pool, and we discuss the applicability of this
      approach under both cross-sectional and case-control sampling. We also provide a
      maximum likelihood approach for longitudinal or repeated measures studies where
      the binary outcome and exposure are assessed on multiple occasions and within
      subject pooling is conducted for exposure assessment. Simulation studies
      illustrate the performance of the proposed approaches along with their
      computational feasibility using widely available software. We apply the methods
      to investigate gene-disease association in a population-based case-control study
      of colorectal cancer.

PMID- 22415633
TI  - Laser-nanostructure interactions for ion production.
AB  - Interactions between pulsed laser radiation and nanostructured materials, with
      dimensions ranging from 1 nm to 500 nm, can result in enhanced desorption and
      ionization of organic and biomolecular adsorbates. When the critical dimensions
      of the nanostructures fall below the characteristic lengths for the involved
      transport processes, novel regimes of ion production are observed. Systems with
      dimensions commensurate with the wavelength of the laser radiation are the basis
      of photonic ion sources with unique properties, including polarization dependent
      ion yields and fragmentation. The main characteristics of these systems are often
      governed by altered modes of transport, e.g., ballistic vs. diffusive, energy
      confinement, plasmon resonances, and local field enhancements. Some structures
      offer control over the internal energy and the active fragmentation channels for
      the produced ions. Emerging applications of photonic ion sources in mass
      spectrometry benefit from ultrahigh sensitivity, a wide dynamic range for
      detection and quantitation, and a broad coverage of adsorbates ranging from small
      organic molecules to biopolymers, as well as to highly complex samples like
      single cells. 

PMID- 22415632
TI  - A Bayesian analysis of the 2009 decline in tuberculosis morbidity in the United
      States.
AB  - Although annual data are commonly used to model linear trends and changes in
      trends of disease incidence, monthly data could provide additional resolution for
      statistical inferences. Because monthly data may exhibit seasonal patterns, we
      need to consider seasonally adjusted models, which can be theoretically complex
      and computationally intensive. We propose a combination of methods to reduce the
      complexity of modeling seasonal data and to provide estimates for a change in
      trend when the timing and magnitude of the change are unknown. To assess
      potential changes in trend, we first used autoregressive integrated moving
      average (ARIMA) models to analyze the residuals and forecast errors, followed by
      multiple ARIMA intervention models to estimate the timing and magnitude of the
      change. Because the variable corresponding to time of change is not a statistical
      parameter, its confidence bounds cannot be estimated by intervention models. To
      model timing of change and its credible interval, we developed a Bayesian
      technique. We avoided the need for computationally intensive simulations by
      deriving a closed form for the posterior distribution of the time of change.
      Using a combination of ARIMA and Bayesian methods, we estimated the timing and
      magnitude of change in trend for tuberculosis cases in the United States.
      Published 2012. This article is a US Government work and is in the public domain
      in the USA.

PMID- 22415631
TI  - Identification of novel and conserved Populus tomentosa microRNA as components of
      a response to water stress.
AB  - MicroRNAs (miRNAs) are a class of small, non-coding RNAs that play important
      downregulation roles in plants growth, development, and stress responses. To
      better identify Populus tomentosa miRNAs and understand the functions of miRNAs
      in response to water stress (drought and flooding), 152 conserved miRNAs
      belonging to 36 miRNA families, 8 known but non-conserved miRNAs and 64 candidate
      novel miRNAs belonging to 54 miRNA families were identified and analyzed from
      three small RNA (sRNA) libraries (drought treatment, flooding treatment, and
      control) by high-throughput sequencing combined with qRT-PCR. Significant changes
      in the expression of 17 conserved miRNA families and nine novel miRNAs were
      observed in response to drought stress, and in seven conserved miRNA families and
      five novel miRNAs in response to flooding stress. Both miRNA and miRNA*s were
      involved in the regulation of plant stress responses. The annotation of the
      potential targets of miRNAs with differential expression indicate that many types
      of genes encoding transcription factors, enzymes, and signal transduction
      components are implicated in the abiotic stress response..

PMID- 22415635
TI  - A multivendor phantom study comparing the image quality produced from three state
      of-the-art SPECT-CT systems.
AB  - OBJECTIVE: Ongoing advancements in single photon emission computed tomography
      with on-board X-ray computed tomography (SPECT-CT) hardware and software raise
      important questions regarding the relative performances of various cameras and
      their respective image-processing software. This phantom-based study compares
      images produced from three state-of-the-art cameras using four image quality
      measurements. METHODS: A thorax phantom modeling the spine, lungs, a healthy
      heart, and three tumors (cylindrical bottles) was scanned using the following
      SPECT-CT systems: Philips' Precedence (PP), GE's Infinia-Hawkeye (GH), and
      Siemens' Symbia-T6 (SS). For each scan, Tc-99m solutions were injected into the
      heart, three bottles, and thorax to yield activity concentration ratios of
      roughly 6:1 for both heart:thorax and tumor:thorax. The data were reconstructed
      using the most advanced software available on the cameras, namely, Evolution for
      Bone and Evolution for Cardiac (EVB and EVC, respectively), Astonish (AST), and
      Flash3D (FLA) for GH, PP, and SS, respectively. In addition, all sets of data
      were reconstructed using our in-house software. The mean values of activity
      error, uniformity, signal-to-noise ratio, and contrast error were used as figures
      of merit (FOM). RESULTS: No significant differences were observed for all FOM
      between all in-house reconstructions using PP, GH, and SS acquisition data. The
      mean activity error for the AST reconstruction (-24.0+/-1.6%) was significantly
      closer to the truth relative to EVB (-38.0+/-1.6%), EVC (-34.5+/-2.3%), and FLA (
      33.8+/-1.6%). No significant differences were found between EVC and FLA for all
      FOM. CONCLUSION: In this phantom-based study, Philips' AST provided the most
      quantitatively accurate and highest contrast images, whereas Siemens' FLA and
      GE's EVC provided relatively higher signal-to-noise ratios and more uniform
      images.

PMID- 22415634
TI  - Narrow band imaging of squamous cell carcinoma tumors using topically delivered
      anti-EGFR antibody conjugated gold nanorods.
AB  - BACKGROUND: Nanoparticles have recently gained interest as exogenous contrast
      agents in a variety of biomedical applications related to cancer detection and
      treatment. The objective of this study was to determine the potential of
      topically administered antibody conjugated gold nanorods (GNRs) for imaging
      squamous cell carcinomas (SCCs) of the skin using near-infrared narrowband
      imaging (NBI). Near-infrared (NIR) NBI images narrow wavelength bands to enhance
      contrast from plasmonic particles in a wide field portable and noncontact device
      that is clinically compatible for real-time tumor imaging and tumor margin
      demarcation. STUDY DESIGN: We conjugated GNRs to Cetuximab, a clinically approved
      humanized antibody that targets the epidermal growth factor receptor (EGFR),
      which is overexpressed on the surface of many tumor cells, especially SCCs. We
      excised subcutaneous xenografts of SCCs (A431) from Swiss nu/nu mice and divided
      the tumors into two groups: (1) the targeted group (Cetuximab conjugated GNRs)
      and (2) the control group (polyethylene glycol-conjugated GNRs). After topical
      application of particles and incubation for 30 minutes, the tumors were washed
      and imaged using NBI. In addition, we performed two-photon imaging to quantify
      the binding of EGFR targeted GNRs in tumors and their depth profile. RESULTS: The
      NBI images showed a visual increase in contrast from tumors after topical
      administration of targeted GNR. Targeted GNR tumors showed increased contrast
      compared to tumors administered with the control GNR. There was a statistically
      significant increase in mean pixel intensity (~2.5*) from targeted GNR tumors (n
      = 6). Two-photon microscopy images of targeted GNRs confirmed their binding
      affinity to the EGF receptors over expressed in the A431 tumors. CONCLUSION: We
      have demonstrated that a topical application of gold nanorods targeted
      specifically to tumor growth factor receptors results in a significantly higher
      image contrast compared to nontargeted gold nanorods. These results demonstrate
      the feasibility of near-infrared NBI to image and demarcate tumor margins during
      surgical resection using topical administration of targeted GNR.

PMID- 22415636
TI  - Nanoscale characterization and magnetic reversal mechanism investigation of
      electrospun NiFe2O4 multi-particle-chain nanofibres.
AB  - NiFe(2)O(4) multi-particle-chain nanofibres have been successfully fabricated
      using electrospinning followed by calcination, and their morphology, chemistry
      and crystal structure were characterized at the nanoscale. Individual NiFe(2)O(4)
      nanofibres were found to consist of many nanocrystallites stacked along the
      nanofibre axis. Chemical analysis shows that the atomic ratio of Ni : Fe is 1 :
      2, indicating that the composition was NiFe(2)O(4). The crystal structure of
      individual NiFe(2)O(4) multi-particle-chain nanofibres proved to be
      polycrystalline with a face centered cubic (fcc) structure. The nanocrystallites
      in the nanofibres were revealed to have a single-crystal structure with random
      crystallographic orientations. The magnetic measurements reveal that the
      NiFe(2)O(4) multi-particle-chain nanofibres have a coercivity force of 166 Oe. A
      "chain of sheets" micromagentism model was proposed to interpret the observed
      magnetic behaviour of the NiFe(2)O(4) multi-particle-chain nanofibres. Simulation
      studies of the coercivity are in good agreement with the experimental results at
      room temperature. It is believed that this work will significantly expand the use
      and application of these compounds in the field of biomagnetic nano-devices and
      improve understanding of the magnetic origin of spinel ferrites.

PMID- 22415637
TI  - Serial correlation in optimal design for nonlinear mixed effects models.
AB  - In population modeling two sources of variability are commonly included; inter
      individual variability and residual variability. Rich sampling optimal design
      (more samples than model parameters) using these models will often result in a
      sampling schedule where some measurements are taken at exactly the same time
      point, thereby maximizing the signal-to-noise ratio. This behavior is a result of
      not appropriately taking into account error generation mechanisms and is often
      clinically unappealing and may be avoided by including intrinsic variability,
      i.e. serially correlated residual errors. In this paper we extend previous work
      that investigated optimal designs of population models including serial
      correlation using stochastic differential equations to optimal design with the
      more robust, and analytic, AR(1) autocorrelation model. Further, we investigate
      the importance of correlation strength, design criteria and robust designs.
      Finally, we explore the optimal design properties when estimating parameters with
      and without serial correlation. In the investigated examples the designs and
      estimation performance differs significantly when handling serial correlation.

PMID- 22415638
TI  - Is rational antipsychotic polytherapy feasible? A selective review.
AB  - Antipsychotic polytherapy (APT) has evolved as a common treatment strategy at
      odds with recommendations from schizophrenia treatment guidelines. The literature
      on combinations with clozapine as a means to enhance efficacy and with
      aripiprazole to reduce side effects was reviewed. No solid evidence supporting
      antipsychotic combinations with clozapine for treatment-resistant patients with
      schizophrenia was identified. The reason for this may be that most combinations
      with clozapine increase the D(2)-receptor blockade, and this strategy is probably
      not efficient for patients with treatment-resistant schizophrenia. Some basic and
      clinical evidence for the addition of aripiprazole to lower prolactin levels was
      identified. In conclusion, there is very limited support in the evidence for the
      feasibility of rational APT.

PMID- 22415639
TI  - Ligustrazine phosphate ethosomes for treatment of Alzheimer's disease, in vitro
      and in animal model studies.
AB  - In the present study, we have investigated transdermal administration of
      ligustrazine phosphate (LP), as an antioxidant, for the treatment of Alzheimer's
      disease (AD). The LP transdermal ethosomal system was designed and characterized.
      Franz-type diffusion cells and confocal laser scanning microscopy were used for
      the in vitro permeation studies. Furthermore, the effect of LP transdermal
      ethosomal system on AD was evaluated in the scopolamine-induced amnesia rats by
      evaluating the behavioral performance in the Morris water maze test. The
      activities of the antioxidant enzymes and the levels of the lipid peroxidation
      product malondialdehyde (MDA) in the brain of rats were also determined. The
      results showed that both the penetration ability and the drug deposition in skin
      of the LP ethosomal system were significantly higher than the aqueous one. The LP
      transdermal ethosomal system could recover the activities of the antioxidant
      enzymes and the levels of MDA in the brain of the amnesic rats to the similar
      status of the normal rats, which was also indirectly reflected by the improvement
      in the behavioral performance. In conclusion, LP might offer a potential
      alternative therapeutic drug in the fight against AD, and ethosomes could be
      vesicles of choice for transdermal delivery of LP.

PMID- 22415640
TI  - Quantification of mass transfer during spheronisation.
AB  - Spherical granules (pellets) are quite useful in many pharmaceutical
      applications. The extrusion spheronisation technique is well established as a
      method of producing pellets of a spherical shape and narrow size distribution.
      After the extrusion, the cylindrical extrudates are transformed to spherical
      pellets by spheronisation. The frequently used models consider deformation and
      breakage during this process. However, the adhesion of fine particles has been
      neglected as a mechanism in spheronisation for many years. This study quantifies
      the mass transfer between pellets during spheronisation. During the
      investigation, the pelletisation aids (microcrystalline cellulose and kappa
      carrageenan), the drug (acetaminophen and ibuprofen) and water content were
      varied systematically. A novel parameter, namely, the "mass transfer fraction"
      (MTF), was defined to quantify the mass transfer between the pellets. All four
      investigated formulations had an MTF between 0.10 and 0.52 that implies that up
      to 50 % of the final pellet weight was involved in mass transfer. Both
      pelletisation aids showed similar MTF, independent of the drug used. Furthermore,
      an increase of the MTF, with respect to an increase of the water content, was
      found for microcrystalline cellulose formulations. In conclusion, the mass
      transfer between the pellets has to be considered as a mechanism for
      spheronisation.

PMID- 22415642
TI  - Fluoride in the drinking water of Nagaur tehsil of Nagaur District, Rajasthan,
      India.
AB  - Fluoride concentration of groundwater samples from 100 villages of Nagaur tehsil
      was determined, 85 villages were found to have fluoride concentration more than
      1.5 mg/L. The maximum fluoride concentration was recorded 6.6 mg/L in groundwater
      of Singhani village, while the minimum was recorded in Kurchhi village. As per
      the desirable and maximum permissible limit for fluoride in drinking water,
      determined by World Health Organization, the groundwater of about 85 villages of
      the studied sites is unfit for drinking purpose.

PMID- 22415641
TI  - Immunomodulatory and physical effects of phospholipid composition in vaccine
      adjuvant emulsions.
AB  - Egg phosphatidylcholine is commonly used as an emulsifier in formulations
      administered parenterally. However, synthetic phosphatidylcholine (PC)
      emulsifiers are now widely available and may be desirable substitutes for egg
      derived phospholipids due to stability, purity, and material source
      considerations. In earlier work, we demonstrated that a squalene-1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphocholine (POPC) emulsion provided equivalent physical
      stability compared to a squalene-egg PC emulsion. In the present manuscript, we
      evaluate the physical stability of vaccine adjuvant emulsions containing a range
      of other synthetic phosphatidylcholine emulsifiers. Besides the POPC emulsion,
      the 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) emulsion showed good
      particle size and visual stability compared to emulsions made with other
      synthetic phospholipids. Moreover, comparable immune responses were elicited by
      squalene emulsions employing various synthetic PC or egg PC emulsifiers in
      combination with an inactivated influenza vaccine or a recombinant malaria
      antigen, and these responses were generally enhanced compared to antigen without
      adjuvant. Therefore, we show that (1) some synthetic PCs (DMPC, POPC, and to a
      lesser extent 1,2-dioleoyl-sn-glycero-3-phosphocholine) are effective stabilizers
      of squalene emulsion over a range of storage temperatures while others are not
      (1,2-distearoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine, and 1,2-dilauroyl-sn-glycero-3-phosphocholine) and (2) the
      immunogenicity of stable squalene emulsions is similar regardless of PC source.

PMID- 22415643
TI  - Automated sample clean-up and fraction of organochlorine pesticides in sediments
      using the SPE-GPC-VAP system.
AB  - This paper describes an automated sample clean-up and fraction method using the
      SPE-GPC-VAP system for the determination of organochlorine pesticides (OCPs) in
      sediments. The method is based on a simultaneous extraction/clean-up step to
      reduce analysis time and solvent consumption. The parameters of a solid-phase
      extraction procedure, a gel permeation chromatography procedure and an AccuVap
      procedure were optimized to obtain maximum recovery of the target analytes with
      minimum presence of matrix-interfering compounds. The detection limits ranged
      from 0.03 to 0.13 ng g(-1) and the recovery ranged from 50.05% to 104.39%. The
      relative standard deviation was lower than 19.34% when OCPs concentrations in
      sediments ranged from 1.25 to 125 ng g(-1).

PMID- 22415644
TI  - Lead content in multifloral honey from central Croatia over a three-year period.
AB  - Lead concentrations were analysed by atomic absorption spectrometry in
      multifloral honeys collected in central Croatia (Zagreb County) during a three
      year period from 2009 to 2011. The mean levels of elements (MUg/kg) in honey
      samples measured were: 90.8 in 2009, 189 in 2010 and 360 in 2011. Significant
      differences were observed, and Pb levels determined in 2009 were significantly
      lower than those in 2010 and 2011 (p < 0.05, both). In 2009 there was no
      concentration found above 300 MUg/kg. However, in 2010 and 2011 levels exceeding
      300 MUg/kg were found in 28.6 % and 25 % of samples. Trace element levels of Pb
      determined in multifloral honey were generally higher than concentrations
      obtained from other geographical origins and neighbouring countries. These high
      concentrations of Pb may be related to the fact that the central region is
      becoming increasingly urban and the network of motorways is growing. Accordingly,
      the risk of positioning hives near zones of busy highways and railways is
      increasing. This underlines that particular attention should be paid to toxic Pb
      levels, due to their gradual increased during the study period.

PMID- 22415645
TI  - Metal pollution in seaweed and related sediment of the Persian Gulf, Iran.
AB  - Nickel, cadmium, copper and lead in the sediment and seven species of algae from
      six locations in the Bushehr Province on the Coast of the Persian Gulf were
      determined. Sampling sites represent areas of importance in seaweed harvest and
      areas near sources of anthropogenic pollution. The mean concentrations of metals
      in the sediment (across all six collection sites, and collection periods) were:
      Pb (42.4 +/- 2.7), Cd (7.4 +/- 1), Ni (38.1 +/- 3.7), and Cu (8.3 +/- 1.2) MUg g(
      1) dry weight. High significant positive correlations existed between metals in
      cervicornis, corticata, and pavonica algae and the sediment, suggesting these
      species of algae are suitable for biomonitoring of the area.

PMID- 22415646
TI  - Plastic debris in the digestive tract of sheep and goats: an increasing
      environmental contamination in Birjand, Iran.
AB  - A total of 230 goats and 185 sheep were evaluated in this cross-sectional
      observational study. After emptying the gastrointestinal tract, the size,
      location, adhesion and obstruction were examined. Twenty seven and half percent
      of sheep and 24 point 3 % of goats had foreign bodies. Most foreign bodies were
      plastic materials in sheep and goats. Forty percent of pregnant animals had
      foreign bodies. Drought and lack of adequate pastures in the past years have been
      a major cause of the swallowing of foreign objects by sheep and goats.

PMID- 22415647
TI  - Potential risks of effluent from acid mine drainage treatment plants at abandoned
      coal mines.
AB  - The lethal and sublethal toxicity of effluent from three acid mine drainage
      treatment plants were monitored from August 2009 to April 2010 using Daphnia
      magna (reference species) and Moina macrocopa (indigenous species). Acute lethal
      toxicity was observed in Samma effluent due to incomplete neutralization of acid
      mine drainages by the successive alkalinity producing system (SAPS).
      Additionally, there was no significant difference in toxicity values (TU) between
      D. magna and M. macrocopa (p < 0.05). Toxicity identification results of the
      final effluent collected in January 2010 showed that Al and Zn were key toxicants
      in addition to acidic pH. Unlike the Samma effluent, both Hwangji and Hamtae
      effluent had pH values that were near neutrality and showed either no acute
      toxicity or toxicity values less than 1 TU. However, the feeding rates of D.
      magna and M. macrocopa were significantly reduced when compared to the control (p
      < 0.05). These findings suggest that the Hamtae and Hwangji effluent likely have
      a sublethal effect on aquatic organisms in receiving water bodies.

PMID- 22415648
TI  - Assessment of the levels of persistent organic pollutants and 1-hydroxypyrene in
      blood and urine samples from Mexican children living in an endemic malaria area
      in Mexico.
AB  - The aim of this study was to evaluate the exposure levels to persistent organic
      pollutants and 1-hydroxypyrene in children living in an endemic malaria zone in
      Mexico. The blood levels for 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT),
      1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and lindane ranged from 15.4
      to 17,886.5 ng/g lipid, 6,624.3 to 100,119.0 ng/g lipid, and 351.1 to 6,153.8
      ng/g lipid, respectively. For total polychlorinated biphenyls the blood levels
      ranged from 2,584.9 to 14,547.9 ng/g lipid. Regarding urinary 1-hydroxypyrene
      levels, the mean level was 2.9 +/- 3.1 MUmol/mol creatinine. In conclusion, the
      children in our study are exposed to levels higher than normal to mixtures of
      environmental contaminants.

PMID- 22415649
TI  - Dissipation and residues of myclobutanil in tobacco and soil under field
      conditions.
AB  - Field experiments were conducted in two different locations to determine the
      dissipation pattern and residue levels of myclobutanil in tobacco leaves and
      soil. Myclobutanil 12.5 % microemulsion (ME) formulation was sprayed once at 3.0
      mL/ha, and the residues in green tobacco leaves dissipated to more than 50 % of
      the initial deposits 5 days after application and up to above 90 % after 21 days.
      The dissipation rate of myclobutanil in soil was lower than that in green tobacco
      leaves. The residues dissipated above 50 % of the initial deposits 7 days after
      treatment and dissipated about 90 % after 42 days. The calculated half-life
      values (T (1/2)) were found to be 4.89-6.77 days in green tobacco leaves and
      12.88-19.20 days in soil, respectively. The ultimate residues of myclobutanil in
      flue-cured tobacco leaves and soil were determined after the third and fourth
      applications at levels of 2.0 and 3.0 mL/ha. Myclobutanil residues in cured
      tobacco leaves 21 days after the last treatment ranged from 0.85 to 3.27 mg/kg.
      Meanwhile, the residues detected in soil reached below 0.045 mg/kg 21 days after
      the last treatment.

PMID- 22415650
TI  - A phase 2 study of bevacizumab with cisplatin plus intensity-modulated radiation
      therapy for stage III/IVB head and neck squamous cell cancer.
AB  - BACKGROUND: For patients with stage III through IVB head and neck squamous cell
      carcinoma (HNSCC), concurrent high-dose cisplatin plus radiation therapy is a
      widely accepted standard of care. HNSCC tumors that express high levels of
      vascular endothelial growth factor have been associated with a worse prognosis,
      and bevacizumab may sensitize tumors to cisplatin and radiation. METHODS: Planned
      treatment consisted of definitive intensity-modulated radiation therapy (IMRT)
      (total, 70 grays) with concurrent cisplatin (50 mg/m(2) on days 1, 2, 22, 23, 43,
      and 44) and bevacizumab (15 mg/kg on days 1, 22, and 43). The primary endpoint
      was 2-year progression-free survival (PFS), and overall survival (OS) was a
      secondary endpoint. RESULTS: Forty-two previously untreated patients (34 men and
      8 women; median age, 55 years; range, 27-75 years) with stage III through IV
      HNSCC without distant metastasis (oropharyngeal carcinoma, 39 patients; laryngeal
      carcinoma, 3 patients) were treated. Human papillomavirus (HPV) status by was
      determined by in situ hybridization (HPV positive, 16 patients; HPV negative, 14
      patients, unknown HPV status, 12 patients). The toxicities (determined according
      to version 3.0 of Common Terminology Criteria for Adverse Events Common) that
      were experienced by all patients (any grade) were mucositis, lymphopenia,
      leukopenia, throat pain, fatigue, and anemia. There were 2 treatment-related
      deaths, including 1 sudden death and 1 death from aspiration pneumonia. The
      median follow-up was approximately 31.8 months (range, <3 to 51 months). The 2
      year PFS rate was 75.9% (95% confidence interval, 63.9%-90.1%), and the 2-year OS
      rate was 88% (95% confidence interval, 78.6%-98.4%). Among 32 patients for whom
      post-treatment Head and Neck Performance Status Scores were obtained (median, 5.6
      months after completing radiation therapy), scores of 100 for eating, speech, and
      diet, respectively, were recorded among 75%, 84%, and 50% of patients.
      BACKGROUND: The addition of bevacizumab to high-dose cisplatin plus IMRT did not
      appear to increase toxicity to unacceptable levels among patients with HNSCC, and
      the efficacy results were encouraging.

PMID- 22415651
TI  - A questionnaire on the educational system for pancreatoduodenectomy performed in
      1,134 patients in 71 institutions as members of the Japanese Society of
      Pancreatic Surgery.
AB  - BACKGROUND/PURPOSE: Mastering the technique of pancreaticoduodenectomy (PD) is a
      major theme in hepato-biliary-pancreatic surgery, and education for PD has not
      been established even in each institution. With the progression of disease, the
      difficulty of PD increases due to cases requiring resection of multiple organs
      and borderline resectable cases, and complications affecting survival also often
      occur. To help to improve the education of young surgeons, we clarified the
      institutions' principles and the status of operations performed by young
      surgeons. METHODS: We sent questionnaires to institutions as members of the
      Japanese Society of Pancreatic Surgery about the institutions' educational
      principles in 2010 and surgeons who performed PD and patients treated by PD
      between January and December 2007. The PD operators were classified into two
      groups: postgraduate year <= 10 or >= 11, and each institution's principles, and
      pre-, intra-, and postoperative factors were evaluated. RESULTS: PD was performed
      by surgeons at postgraduate year <= 10 in 29 (40.6%) institutions. Education
      programs were using 29 (41.4%) institutions. High-volume centers, where the
      surgeons performing PD tend to be at postgraduate year <= 10, can provide more
      training. Preoperative risks were not included in the criteria for selecting
      cases for operations by young surgeons, and young surgeons tended to perform PD
      in patients with less advanced stages. The incidence of pancreatic fistula
      classified as International Study Group of Pancreatic Surgery Grade B or C was
      significantly higher (P = 0.010) in the operator group at postgraduate year <= 10
      (24.6%, 32 patients) than that at postgraduate year >= 11 (17.6%, 177 patients).
      Cumulative survival rate of pancreatic cancer or extrahepatic bile duct cancer
      did not significantly differ between the two operator groups. CONCLUSION: The
      present questionnaire showed increased opportunities of performing operations by
      young surgeons. Although the incidence of Grade B/C fistula is higher for
      postgraduate year <= 10, postoperative outcome is acceptable. It is acceptable
      for the pancreaticoduodenectomy performed by young surgeons, when young surgeons
      receive high-level education under the guidance of supervisory doctor. Prognosis
      did not differ between two operator groups at postgraduate year <= 10 and >= 11
      in this study. Based on these findings, operations by surgeons at postgraduate
      year <= 10 present can be recommended.

PMID- 22415652
TI  - Metallic stents are more efficacious than plastic stents in unresectable
      malignant hilar biliary strictures: a randomized controlled trial.
AB  - BACKGROUND: Endoscopic biliary stenting is a well-established palliative
      treatment for unresectable malignant biliary strictures, for which plastic tube
      stents (PSs) and self-expandable metallic stents (SEMSs) are most commonly used.
      The efficacy of these stents has been extensively described in distal biliary
      strictures, but not in hilar biliary strictures. The present study aimed to
      compare the efficacy of PSs and SEMSs for unresectable malignant hilar biliary
      strictures. METHODS: From June 2004 to November 2008, 60 patients were enrolled
      and prospectively randomized into the PS or SEMS group. RESULTS: The 6-month
      patency rate was significantly higher in the SEMS group than in the PS group (81
      vs. 20%; p = 0.0012). Kaplan-Meier analysis showed significantly longer patency
      in the SEMS group than in the PS group (p = 0.0002); the 50% patency period was
      359 days in the SEMS group and 112 days in the PS group. There was no significant
      difference in the overall survival period between the PS and SEMS groups (p =
      0.2834). The mean number of reinterventions for stent failures was significantly
      lower in the SEMS group (0.63 times/patient) than in the PS group (1.80
      times/patient) (p = 0.0008). The overall total cost for the treatment was
      significantly lower in the SEMS group than in the PS group (p = 0.0222).
      CONCLUSIONS: SEMSs were associated with a longer patency than PSs in patients
      with unresectable hilar biliary stricture. SEMSs were also more advantageous in
      reducing the number of reintervention sessions and the overall treatment cost.

PMID- 22415653
TI  - Effect of Cissampelos pareira root extract on isoproterenol-induced cardiac
      dysfunction.
AB  - The aim of this study was to assess the cardioprotective effect of Cissampelos
      pareira root extract on isoproterenol-induced cardiac dysfunction in rats. Male
      albino Wistar rats were randomly divided into eight groups and received either
      normal saline (0.5 ml/kg, intraperitoneally), isoproterenol (5 mg/kg,
      intraperitoneally), C. pareira (100 and 200 mg/kg, by gavage, respectively)
      alone, amlodipine (9 mg/kg, by gavage) alone, C. pareira (100 and 200 mg/kg,
      respectively) + isoproterenol and amlodipine (9 mg/kg) + isoproterenol, once a
      day for 30 days, respectively. Isoproterenol-induced cardiac dysfunction was
      characterized by a significant (P < 0.001) increase in the heart weigh/body
      weight ratio, serum calcineurin, nitric oxide, lactate dehydrogenase, and
      thiobarbituric acid reactive substance levels, as well as a significant decrease
      in serum-reduced glutathione, cardiac glutathione peroxidase, glutathione
      reductase, and glutathione-S-transferase levels, which were significantly (P <
      0.05 and P < 0.01) improved by C. pareira treatment. No significant alteration
      was observed in the group treated with C. pareira alone compared with the
      control. C. pareira treatment also restored histopathological changes observed in
      isoproterenol-induced rats. Amlodipine is used as standard drug in this study.
      Thus, these results suggest that the attenuation of isoproterenol-induced cardiac
      dysfunction by treatment with ethanolic root extract of C. pareira may be due to
      amelioration of calcineurin activity and free radical formation, and by
      augmentation of antioxidant enzymes activities.

PMID- 22415654
TI  - Simultaneous determination of heavy metal pollution in commercial traditional
      Chinese medicines in China.
AB  - A rapid and accurate method of quantifying heavy metal pollution in commercial
      traditional Chinese medicines (TCMs) is described. The method uses modified wet
      digestion for sample preparation and atomic absorption spectrophotometry for
      detecting the content of copper (Cu), cadmium (Cd), arsenic (As), lead (Pb) and
      mercury (Hg). The determination limits of the method were 0.001, 0.002, 0.001,
      0.001 and 0.001 mg/kg for Cu, Cd, As, Pb and Hg, respectively. The method was
      applied to the quantification of heavy metal pollution in 50 different commercial
      TCMs in a total of 250 samples. Heavy metal contents in the samples investigated
      were found at different levels. The level of As did not exceed the legal limit
      stated in the China pharmacopoeia 2010, whereas Cu, Cd, Pb and Hg were above
      permitted levels in some samples.

PMID- 22415656
TI  - [Prevention of bone mineral deficiency in premature infants: review of the
      literature with focus on monitoring of urinary calcium and phosphate].
AB  - BACKGROUND: Bone mineral deficiency of prematurity (BMDoP) is caused by the lack
      of simultaneous availability of calcium (Ca) and anorganic phosphate (P) during
      rapid skeletal growth. METHODS: Review of the literature on the prevention of
      BMDoP, with specific attention to the limitations of the monitoring of urinary
      calcium and phosphate concentrations. RESULTS: Intrauterine bone mineral
      accretion (BMA) can be achieved in preterm infants if urinary concentrations of
      Ca and P continuously show that the supplementation with these ions slightly
      exceeds the actual need. An individually adjusted supplementation with Ca and P
      appears rational because both growth velocity and enteral Ca absorption are
      highly variable and determine the need for enteral Ca and P administration. If,
      however, urinary concentrations of Ca and P are used to determine whether Ca and
      P supplementation is adequate, mechanisms affecting the urinary excretion of
      these ions other than nutrition have to be taken into account. Specifically,
      methylxanthines and diuretics increase the renal Ca losses, and the renal P
      threshold may be lowered in premature infants. A positive effect of physical
      activity on BMA has been shown in several studies. CONCLUSIONS: An individualized
      Ca and P supplementation in preterm infants aiming for supplementation in a
      slight excess of the actual need and guided by urinary Ca and P concentrations
      appears able to prevent BMDoP. Monitoring of urinary Ca and P concentrations
      needs to take into account non-nutritional factors affecting these
      concentrations. BMA may further be improved by physical activity.

PMID- 22415657
TI  - What are the best outcome measures when assessing treatments for LUTD?--achieving
      the most out of outcome evaluation: ICI-RS 2011.
AB  - A think tank was convened at the third ICI-RS meeting held in the UK, June 2011,
      to consider the best outcome measures when assessing treatments for lower urinary
      tract dysfunction (LUTD). Given the vast array of measures available a focus on
      questionnaires was decided upon, which continued to highlight a plethora of
      available tools. The decision was therefore taken to approach this topic from an
      alternative perspective and instead ask the audience of gathered experts in this
      field to consider, "What we need to ask as a minimum in order to capture the most
      fundamental parameters when evaluating new treatments for LUTD?" Discussions
      highlighted the need for inclusion of a global measure in all outcome evaluations
      in order to increase comparability between different treatment evaluations and
      different populations. More specific categories of evaluation identified were:
      treatment satisfaction, symptom quantification, health related quality of life
      and adverse events. Further optional components were identified for inclusion
      where relevant, such as health economic, goal setting and psychosocial
      evaluation. A "Minimum Outcome Set for Testing (MOST)" was therefore proposed by
      selecting a health outcome measure from each category while not being
      prescriptive about specific outcome measurement selection. The 'MOST' toolkit is
      therefore proposed to promote standardized evaluation in this field and
      represents a useful starting point for further consideration of this concept.

PMID- 22415658
TI  - Synthesis and biological evaluation of 1-phenyl-1,2,3,4-dihydroisoquinoline
      compounds as tubulin polymerization inhibitors.
AB  - A series of 1-phenyl-3,4-dihydroisoquinoline derivatives and several 1-phenyl
      1,2,3,4-tetrahydroisoquinoline, 1-phenyl-isoquinoline analogues were synthesized,
      and their cytotoxicity and tubulin polymerization inhibitory activity were
      evaluated. The 1-phenyl-3,4-dihydroisoquinoline compounds were found to be
      potential tubulin polymerization inhibitors. Compound 5n, bearing a 3'-OH and 4'
      OCH(3) substituted 1-phenyl B-ring, was shown to confer optimal bioactivity. The
      single-crystal structure of 5n was further determined by X-ray diffraction, and
      the binding mode of 5n to tubulin was obtained by molecular docking, which can
      explain the structure-activity relationships. The studies presented here provide
      a new structural type for the development of novel antitumor agents.

PMID- 22415659
TI  - Midkine upregulates MICA/B expression in human gastric cancer cells and decreases
      natural killer cell cytotoxicity.
AB  - Midkine (MK) is a heparin-binding growth factor overexpressed in various human
      cancers. In the current study, a positive correlation was observed between MK
      expression and MICA/B serum levels of gastric cancer patients. In addition, MK
      transfection significantly increased MICA/B expression in gastric cancer cells.
      The soluble MICA/B expression was also elevated. Furthermore, MK transfection
      inhibited CD107a and Granzyme B expression, thereby suppressing the natural
      killer (NK) cell cytotoxicity in vitro. The phosphorylation of p38 MAPK and its
      promotion of CHOP expression were also observed after MK treatment and
      transfection. CHOP was indirectly bound to the MICA/B promoter region by
      interacting with AP-1, leading to MICA/B transcription. Overall, the current
      study shows that MK expression in tumor cells indirectly suppresses NK
      cytotoxicity by inducing MICA/B expression and suppressing NKG2D expression.

PMID- 22415660
TI  - Prognostic factors in civilian gunshot wounds to the head: a series of 110
      surgical patients and brief literature review.
AB  - This study was carried out to evaluate the early results and the prognostic
      factors affecting the outcome during the in-hospital stay of 110 patients with
      civilian gunshot wounds to the head admitted at the Hospital of Restauracao,
      Recife, Brazil. Penetrating injury (66%) was the most prevalent type of wound
      encountered in the present series. Twelve of the 110 (10.9%) patients presented a
      unilateral dilated pupil at the admission. Motor impairment was present in 24/110
      (21.8%) patients. Intracerebral hematoma was present in 36/110 (32.7%) and there
      were 15/110 (13%) patients with cerebrospinal fluid fistula. Eleven of 110
      patients developed meningitis and in 9/110 intracranial abscesses occurred. Nine
      of 110 patients developed deep venous thrombosis, 11/110 had urinary infection,
      and coagulopathy was detected in 8/110. Following the surgical procedure, 27/110
      (24.5%) patients died during their hospital stay. When the two groups, survivors
      and non-survivors, were compared, there were significant statistical differences
      and the univariate analysis identified five preoperative predictors of a poor
      outcome following surgery: age over 40 years (odds ratios (OR) 5.4, 95% CI 1.73
      16.82); presence of unilateral pupil dilatation (OR 5.5, 95% CI 1.641-18.13); low
      (<=8) Glasgow coma score on admission (OR 6.50, 95% CI 2.27-18.60), presence of
      intracranial hematoma (OR 3.0, 95% CI 1.21-7.34), and respiratory infection (OR
      4.8, 95% CI 1.75-13.47). Thus, (a) age of the patient (juvenile/young age), (b)
      high preoperative Glasgow coma score, (c) lack of pupil abnormalities, and (d)
      absence of intracerebral hematoma are predictors of a good prognosis.

PMID- 22415661
TI  - Piecewise exponential survival times and analysis of case-cohort data.
AB  - Case-cohort designs select a random sample of a cohort to be used as control with
      cases arising from the follow-up of the cohort. Analyses of case-cohort studies
      with time-varying exposures that use Cox partial likelihood methods can be
      computer intensive. We propose a piecewise-exponential approach where Poisson
      regression model parameters are estimated from a pseudolikelihood and the
      corresponding variances are derived by applying Taylor linearization methods that
      are used in survey research. The proposed approach is evaluated using Monte Carlo
      simulations. An illustration is provided using data from the Alpha-Tocopherol,
      Beta-Carotene Cancer Prevention Study of male smokers in Finland, where a case
      cohort study of serum glucose level and pancreatic cancer was analyzed.

PMID- 22415662
TI  - Can the new American Joint Committee on Cancer staging system predict survival in
      rectal cancer patients treated with curative surgery following preoperative
      chemoradiotherapy?
AB  - BACKGROUND: Although ypStage has been known as a strong prognosticator of
      recurrence and survival, the detailed interaction of ypT and ypN classification
      on a survival rate has never been evaluated. METHODS: Between October 2001 and
      December 2007, in total, 960 patients with locally advanced rectal cancer were
      enrolled retrospectively at 3 centers. Five-year overall survival (OS) and
      disease-free survival (DFS) rate were calculated for each ypTN classification.
      RESULTS: The ypT classification interacted with ypN classification to affect
      survival in most categories. Patients with ypStage 0 and I cancers showed a >90%
      5-year OS (ypStage 0, 96.5%; ypStage I, 92.9%; P = .346) and 5-year DFS (ypStage
      0, 90.2%; ypStage I, 90.7%; P = .879). Among ypStage III subgroups, large
      differences in 5-year OS (ypStage IIIA, 90.1%; ypStage IIIB, 68.3%; ypStage IIIC,
      40.5%; P < .001) and 5-year DFS (ypStage IIIA, 74.8%; ypStage IIIB, 55.1%;
      ypStage IIIC, 12.3%; P < .001) were observed. OS and DFS in patients with ypStage
      IIIA disease were similar to or greater than those in patients with ypStage IIA
      or IIB/IIC disease. Four patient risk groups were defined: 1) low (ypT0-isN0,
      ypT1N0, ypT2N0), 2) intermediate (ypT0-2N1, ypT3N0), 3) moderately high (ypT0
      2N2, ypT3N1, ypT4N0), and 4) high risk (ypT3N2, ypT4N1-2). Risk grouping showed a
      narrower range of survival rate compared with ypStage grouping. CONCLUSIONS:
      ypStage in rectal cancer, defined according to the 7th edition of the American
      Joint Committee on Cancer staging system, predicts survival for most ypNT
      classifications. However, patients with ypStage I rectal cancer have a similar
      prognosis to those with ypStage 0 cancer, and risk grouping reflects more precise
      survival outcomes than ypStage.

PMID- 22415663
TI  - Edge effects control helical wrapping of carbon nanotubes by polysaccharides.
AB  - Carbon nanotubes (CNTs) wrapped by polysaccharide chains via noncovalent
      interactions have been shown to be soluble and dispersed in aqueous environments,
      and have several potential chemical and biomedical applications. The wrapping
      mechanism, in particular the role played by the end of the CNT, remains, however,
      unknown. In this work, a hybrid complex formed by an amylose (AMYL) chain and a
      single-walled carbon nanotube (SWNT) has been examined by means of atomistic
      molecular dynamics (MD) simulations to assess its propensity toward self
      assembly, alongside its structural characteristics in water. To explore edge
      effects, the middle and end regions of the SWNT have been chosen as two initial
      wrapping sites, to which two relative orientations have been assigned, i.e.
      parallel and orthogonal. The present results prove that AMYL can wrap
      spontaneously around the tubular surface, starting from the end of the SWNT and
      driven by both favorable van der Waals attraction and hydrophobic interactions,
      and resulting in a perfectly compact, helical conformation stabilized by an
      interlaced hydrogen-bond network. Principal component analysis carried out over
      the MD trajectories reveals that stepwise burial of hydrophobic faces of pyranose
      rings controlled by hydrophobic interactions is a key step in the formation of
      the helix. Conversely, if wrapping proceeds from the middle of the SWNT, self
      organization into a helical structure is not observed due to strong van der Waals
      attractions preventing the hydrophobic faces of the AMYL chain generating enough
      contacts with the tubular surface.

PMID- 22415664
TI  - Significance of histomorphology of early triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) is a heterogeneous disease. Possibly genetic
      characterisation provides the most appropriate information on tumour biology and
      prognosis, but it is only limitedly available in clinical practice. The aim of
      this investigation was to explore what additional prognostic information could be
      gained from detailed histomorphologic report. PATIENTS AND METHOD: patients were
      selected retrospectively operated from 2005 to 2009 in one institution and charts
      were revised. Beyond age, tumour and nodal status, histologic grade and therapy,
      the additional pathologic characteristics were also involved in analysis:
      necrosis, lymphocytic infiltration, peritumoural vascular invasion (PVI),
      perineural invasion, DCIS extent and grade, perinodal spread, mitotic activity
      index (MAI). RESULTS: 295 early TNBC were involved. In univariate survival
      analysis with a mean follow-up of 3.57 years the tumour size, the nodal status,
      type of operation (conservation or mastectomy), irradiation, PVI and perinodal
      spread proved to be significantly connected with both disease free survival (DFS)
      and breast cancer specific overall survival (BSOS), and necrosis and chemotherapy
      with BSOS. Necrosis analysed together with lymphocytic infiltrate showed greater
      predicting power. In multivariate analysis nodal metastasis, necrosis
      positive/lymphacytic infiltration negative status and lack of irradiation has
      significant negative impact on DFS (p = <0.0001 HR:1.98 [1.4-2.77], p = <0.017
      HR:2.1 [1.1-3.8], p = <0.001 HR:0.25 [0.11-0.57], respectively) and BSOS (p =
      <0.0001 HR:2.47 [1.8-3.4], p = <0.017 HR:3.7 [1.6-8.2], p = <0.0017 HR:0.24 [0.1
      0.58], respectively). For DFS perivascular invasion also showed significant
      effect (p = <0.042 HR:2.5 [1.0-6.0]). Nodal status was the strongest prognostic
      parameter but other histomorphologic parameters can be used for prognosis
      prediction.

PMID- 22415665
TI  - Sterile inflammatory response in acute pancreatitis.
AB  - The initial injury in acute pancreatitis is characteristically sterile and
      results in acinar cells necrosis. Intracellular contents released from damaged
      cells into the extracellular space serve as damage-associated molecular patterns
      (DAMPs) that trigger inflammation. There is increasing evidence that this sterile
      inflammatory response mediated through DAMPs released from necrotic acinar cells
      is a key determinant of further pancreatic injury, remote organ injury, and
      disease resolution in experimental models. A number of DAMPS, including high
      mobility group box protein 1, DNA, adenosine triphosphate and heat shock protein
      70, have been shown to have a role in experimental pancreatitis. Many of these
      DAMPs are also detectable in the human pancreatitis. Genetic deletion and
      pharmacologic antagonism demonstrate that specific DAMP receptors, including Toll
      like receptor (TLR) 4, TLR9, and P2X7, are also required for inflammation in
      experimental acute pancreatitis. Downstream DAMP-sensing components include nod
      like receptor protein 3, caspase 1, interleukin-1beta (IL-1), IL-18, and IL-1
      receptor, and also are required for full experimental pancreatitis. These DAMP
      mediated pathways provide novel therapeutic targets using antagonists of TLRs and
      other receptors.

PMID- 22415666
TI  - Multicenter study of serous cystic neoplasm of the Japan pancreas society.
AB  - OBJECTIVES: There have been only a few reports on follow-up results of serous
      cystic neoplasm (SCN) of the pancreas. The frequency of malignancy and surgical
      indication of SCN are not determined yet. METHODS: In this multi-institutional
      study of the Japan Pancreas Society, a total of 172 patients with SCN were
      enrolled. The mean follow-up period was 4.5 years. Surgical resection was
      performed in 90 patients, whereas the remaining 82 were simply observed. RESULTS:
      Of all patients, 20% were symptomatic. The tumor was located in the pancreatic
      head (39%), body (35%), and tail (22%). The mean diameter of the tumor was 4.1
      cm. None of the patients showed distant or lymph node metastasis except for liver
      metastasis found in 2 patients (1.2%). No patient died during the follow-up. The
      preoperative diagnosis did not correctly identify SCN in 57 (63%) of 90 resected
      cases. A honeycomb appearance, which is one of the most characteristic findings
      of SCN, could be diagnosed better by endoscopic ultrasonography than by other
      imaging diagnostic modalities. CONCLUSIONS: Surgical resection should be
      considered only when clear distinction from other surgical diseases is difficult,
      when symptoms or mass effects are present, and when the tumor size is large.

PMID- 22415667
TI  - Pancreatic stellate cells do not exhibit features of antigen-presenting cells.
AB  - OBJECTIVES: Major histocompatibility complex (MHC) class II molecules are
      expressed on professional antigen-presenting cells (APCs), and pancreatic
      stellate cells (PSCs) have endocytic and phagocytic functions and play a role in
      the immune responses of the pancreas. The aim of the present study was to
      investigate whether PSCs exhibit features of APCs. METHODS: Rat and human PSCs
      were cultured with interferon-gamma (IFN-gamma) or an exogenous antigen,
      ovalbumin (OVA), and they were analyzed for expression of MHC II molecules by
      flow cytometry and reverse transcription-polymerase chain reaction. RESULTS: The
      cells simulated with IFN-gamma expressed very little or no MHC class II molecules
      or human leukocyte antigen (HLA)-DR at the transcriptional level. Stimulation
      with IFN-gamma failed to induce expression of MHC class II molecules and HLA-DR
      molecules according to the results of flow cytometry. Dual-color flow cytometric
      analysis showed that approximately 95% of the PSCs took up OVA; however, none of
      the cells that took up OVA expressed MHC class II molecules or HLA-DR molecules.
      CONCLUSIONS: Pancreatic stellate cells do not seem to be responsible for the MHC
      class II-dependent pathway of antigen presentation, suggesting that PSCs do not
      play a role in adaptive immunity as APCs.

PMID- 22415668
TI  - Acute pancreatitis secondary to neuroendocrine pancreatic tumors: report of 3
      cases and literature review.
AB  - Pancreatic tumors (particularly neuroendocrine) are an uncommon cause of acute
      pancreatitis (AP). This is a report of 3 cases of acute pancreatitis secondary to
      advanced neuroendocrine tumors and a literature review. Including these cases,
      only 30 have been reported. Most cases are non-functioning, diagnosed in an
      advanced stage, associating mild pancreatitis and in patients older than forty.
      Pancreatic neuroendocrine tumors are an uncommon cause of AP but must be included
      in the differential diagnosis of this disease, especially if the patient is older
      than 40 and the etiology of the AP is not clear.

PMID- 22415669
TI  - Coculture of insulin-producing RIN5AH cells with neural crest stem cells protects
      partially against cytokine-induced cell death.

PMID- 22415670
TI  - Long-term disease control with sunitinib in a patient with metastatic pancreatic
      neuroendocrine tumor (NET) associated with Von Hippel-Lindau syndrome (VHL).

PMID- 22415671
TI  - Soluble IL-2 receptor, a new marker for autoimmune pancreatitis.

PMID- 22415672
TI  - Exploring protein kinase inhibitors: potentiating gemcitabine efficacy in
      pancreatic cancer.

PMID- 22415673
TI  - In vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) in
      solid pseudopapillary tumor of the pancreas.

PMID- 22415674
TI  - Synchronous extrapancreatic malignant papillary mucinous neoplasms in a patient
      with intraductal papillary mucinous neoplasm of the pancreas: a rare case of
      simultaneous pancreatic, hepatic, and pulmonary involvement.

PMID- 22415675
TI  - Pancreatic metastases from a bronchopulmonary carcinoid diagnosed by endoscopic
      ultrasonography-guided fine-needle tissue acquisition.

PMID- 22415676
TI  - Stone management for the patient on anticoagulation.
AB  - Use of chronic anticoagulation has increased recently, leading to more surgical
      intervention on patients taking chronic anticoagulation. This review discusses
      anticoagulation and the management of urolithiasis.

PMID- 22415677
TI  - Density functional theory study of nitrogen-14 nuclear quadrupole coupling
      parameters of L-histidine: hydrogen-bonded system.
AB  - The calculations of nitrogen-14 nuclear quadrupole parameters, nuclear quadrupole
      coupling constant, chi, and asymmetry parameter, eta, of L-His were done in two
      distinct environments: one as a free fully optimized molecule, an isolated
      molecule with the geometrical parameters taken from X-ray, and the other in the
      orthorhombic and monoclinic solid states. The most probable interacting molecules
      with the central molecule in the crystalline phase were considered in the
      hexameric clusters to include hydrogen-bonding effects in the calculations. The
      computations were performed with PW91P86/6-31++G** and B3LYP6-31++G** methods
      using the Gaussian 98 program. The good agreement between the nitrogen-14
      quadrupole parameters of the free His and imidazole molecules with their
      microwave available data demonstrates that the applied level of theory and the 6
      31++G** basis set are suitable to obtain reliable electric field gradient values.
      In the solid state, the shifts of quadrupole coupling parameters from the monomer
      to the solid phase are reasonably well reproduced for the amino and imino sites
      of imidazole ring in a hexameric cluster. That implies the fact that the
      hexameric cluster worked effectively to generate the results which are compatible
      with the experiment. The quadrupole coupling constant values of -N(+) H(3) group
      are in fair agreement with the experiment. This discrepancy is due to the
      absences of vibrational effects and the rotation of -N(+) H(3) group around N
      C(alpha) bond.

PMID- 22415679
TI  - RNA silencing and its application in plants.

PMID- 22415678
TI  - The application of dexmedetomidine in children undergoing vitreoretinal surgery.
AB  - PURPOSE: Dexmedetomidine is a highly selective alpha-2 adrenergic agonist that
      has a sedative effect and has been shown to reduce anesthetic requirements. It
      also has a sympatholytic effect, which may prove useful when used to blunt the
      sympathetic surge during intubation and extubation. However, its effects on
      intraocular pressure, hemodynamic stability, attenuation of extubation response,
      and emergence agitation remain unclear for pediatric patients undergoing
      vitreoretinal surgery. We focused on these effects in this study. METHODS: Sixty
      ASA I-II patients undergoing vitreoretinal surgery, were anesthetized with
      sevoflurane 1-2% end-tidal concentration in oxygen supplemented by remifentanil
      0.2 MUg/kg/min. Intraocular pressure was measured after inhalation of sevoflurane
      (IOP(Baseline)) and 10 min after intravenous administration of dexmedetomidine
      0.5 MUg/kg or normal saline (IOP(10min)), after induction of anesthesia. Blood
      pressure and heart rate were recorded every 5 min during surgery. The incidence
      and severity of coughing and emergence agitation and untoward airway events after
      extubation, for example breath holding, laryngospasm, bronchospasm, and oxygen
      desaturation, were assessed. Extubation time and emergence time were also
      documented. RESULTS: There was no significant difference in intraocular pressure
      at the two time points between the groups (p > 0.05). In both groups mean
      arterial pressure and heart rate decreased from baseline after anesthetic
      induction (p < 0.05). The increase from intraoperative values in mean arterial
      pressure and heart rate associated with extubation was diminished in the
      dexmedetomidine group compared with the control group (p < 0.05). Coughing after
      extubation was less common (10 vs. 21) and less severe (3 moderate and 7 minimal;
      vs. 2 severe, 7 moderate and 12 minimal) in the dexmedetomidine group than in the
      control group (p < 0.05). There were no significant differences between the
      groups in time to emergence or extubation (p > 0.05). The dexmedetomidine group
      had a lower incidence of emergence agitation than the control group (10 vs.
      43.3%, p < 0.05). The incidence of breath holding, laryngospasm, bronchospasm and
      oxygen desaturation was not significantly different between the groups (p >
      0.05). CONCLUSIONS: Dexmedetomidine 0.5 ug/kg had no effect on intraoperative
      hemodynamics or intraocular pressure, but attenuated the hemodynamic response to
      extubation and diminished emergence agitation in pediatric patients undergoing
      vitreoretinal surgery.

PMID- 22415680
TI  - Virus-induced gene silencing and its application in plant functional genomics.
AB  - Virus-induced gene silencing is regarded as a powerful and efficient tool for the
      analysis of gene function in plants because it is simple, rapid and
      transformation-free. It has been used to perform both forward and reverse
      genetics to identify plant functional genes. Many viruses have been developed
      into virus-induced gene silencing vectors and gene functions involved in
      development, biotic and abiotic stresses, metabolism, and cellular signaling have
      been reported. In this review, we discuss the development and application of
      virus-induced gene silencing in plant functional genomics.

PMID- 22415681
TI  - Viral suppression of RNA silencing.
AB  - Gene silencing (RNA silencing) plays a fundamental role in antiviral defense in
      plants, fungi and invertebrates. Viruses encode proteins that suppress gene
      silencing to counter host defense. Viral suppressors of RNA silencing (VSRs) have
      been identified from almost all plant virus genera and some viruses of insects
      and mammals. Recent studies have revealed that VSRs counter host defense and
      interfere with host gene regulation by interacting with RNA or important
      components of the RNA silencing pathway. Here, we review the current
      understanding of the complex mechanisms of VSRs that have been revealed by recent
      studies.

PMID- 22415682
TI  - The role of virus-derived small interfering RNAs in RNA silencing in plants.
AB  - Antiviral defense is one of the important roles of RNA silencing in plants. Virus
      derived small interfering RNAs (vsiRNAs) are found in the infected host cells,
      indicating that the host RNA silencing machinery can target viral RNAs for
      destruction. With the development of high-throughput sequencing of vsiRNAs,
      recent genetic studies have shed light on the origin and composition of vsiRNAs
      and their potential functions in the regulation of gene expression. Here, we
      briefly describe the origin and biogenesis of vsiRNAs, and review the recent
      discoveries regarding vsiRNA-mediated RNA silencing of viral genomes and host
      transcripts. This will better our understanding of virus pathogenicity and RNA
      silencing-related host-pathogen interactions in plants.

PMID- 22415683
TI  - Identification of a suitable endogenous control gene in porcine blastocysts for
      use in quantitative PCR analysis of microRNAs.
AB  - To obtain reliable results in quantitative PCR (qPCR) reactions, an endogenous
      control (EC) gene is needed to correct for systematic variations. In this study,
      a TaqMan low density array was used to quantify the expression levels of microRNA
      (miRNA) genes in in vivo fertilized, in vitro fertilized, parthenogenetic and
      somatic cell nuclear transfer blastocysts. The aim was to identify suitable EC
      genes for the qPCR analysis of miRNAs in porcine blastocysts. The results showed
      that thirty-six miRNAs were commonly expressed in the four kinds of embryos and
      the expression levels of eleven miRNAs were similar in the different embryo types
      (P-value>0.05). These 11 miRNAs were selected as candidate EC genes for further
      analysis and, of these, miR-16 was identified as the most stable EC gene by the
      GeNorm (a tool based on a pair-wise comparison model that calculates the internal
      control genes stability measure and determines the most reliable pair of EC
      genes) and NormFinder (an excel plug-in that uses an ANOVA-based model to
      estimate intra- and inter-group variation to indicate the single most stable EC
      gene) programs. In addition, a cell number normalization method validated miR-16
      as a suitable EC gene for use in future qPCR analysis of miRNAs in porcine
      blastocysts.

PMID- 22415684
TI  - Therapeutic effects of human amniotic epithelial cell transplantation on double
      transgenic mice co-expressing APPswe and PS1DeltaE9-deleted genes.
AB  - Human amniotic epithelial cells (HAECs), which exhibit characteristics of
      embryonic and pluripotent stem cells, could be utilized for cell therapy without
      legal or ethical problems. Double-transgenic (TG) mice (n=20) and wild-type (WT)
      mice (n=20) were randomly assigned to two groups, respectively. The
      transplantation group was treated with HAECs and the control group with PBS. A
      six-radial arm water maze was used to assess spatial memory. Immunofluorescence
      was utilized to track HAEC survival. Immunohistochemistry was used to determine
      octamer-binding protein 4 (oct-4) and nanog expression in the HAECs. High
      performance liquid chromatography (HPLC) was used to measure acetylcholine levels
      in the hippocampus. The density of cholinergic neurons in the basal forebrain and
      nerve fibers in the hippocampus was measured following acetylcholinesterase
      staining. Results showed that transplanted HAECs survived for at least eight
      weeks and migrated to the third ventricle without immune rejection. Graft HAECs
      also expressed the specific stem cell markers oct-4 and nanog. Compared with the
      control group, HAEC transplantation significantly ameliorated spatial memory
      deficits in TG mice, as well as increased acetylcholine levels and the number of
      hippocampal cholinergic neurites. Intracerebroventricular HAEC transplantation
      improved spatial memory in double-TG mice, and results suggested that increased
      acetylcholine levels in the hippocampus, released by surviving cholinergic
      neurites, were responsible for this improvement.

PMID- 22415685
TI  - Identification of the novel recessive gene pi55(t) conferring resistance to
      Magnaporthe oryzae.
AB  - The elite rice cultivar Yuejingsimiao 2 (YJ2) is characterized by a high level of
      grain quality and yield, and resistance against Magnaporthe oryzae. YJ2 showed
      100% resistance to four fungal populations collected from Guangdong, Sichuan,
      Liaoning, and Heilongjiang Provinces, which is a higher frequency than that shown
      by the well-known resistance (R) gene donor cultivars such as Sanhuangzhan 2 and
      28zhan. Segregation analysis for resistance with F(2) and F(4) populations
      indicated the resistance of YJ2 was controlled by multiple genes that are
      dominant or recessive. The putative R genes of YJ2 were roughly tagged by SSR
      markers, located on chromosomes 2, 6, 8, and 12, in a bulked-segregant analysis
      using genome-wide selected SSR markers with F(4) lines that segregated into 3
      resistant (R):1 susceptible (S) or 1R:3S. The recessive R gene on chromosome 8
      was further mapped to an interval ~1.9 cM/152 kb in length by linkage analysis
      with genomic position-ready markers in the mapping population derived from an
      F(4) line that segregated into 1R:3S. Given that no major R gene was mapped to
      this interval, the novel R gene was designated as pi55(t). Out of 26 candidate
      genes predicted in the region based on the reference genomic sequence of the
      cultivar Nipponbare, two genes that encode a leucine-rich repeat-containing
      protein and heavy-metal-associated domain-containing protein, respectively, were
      suggested as the most likely candidates for pi55(t).

PMID- 22415686
TI  - Target deletion of the AAA ATPase PpCDC48II in Physcomitrella patens results in
      freezing sensitivity after cold acclimation.
AB  - CDC48 is a highly conserved protein in eukaryotes and belongs to the AAA (ATPase
      associated with a variety of cellular activities) superfamily. It can interact
      with many different co-factors and form protein complexes that play important
      roles in various cellular processes. According to the Physcomitrella patens
      database, one member of the ATPases, the cell cycle gene PpCDC48II, was cloned.
      PpCDC48II contains two typical ATPase modules and is highly homologous to
      AtCDC48A. PpCDC48II was up-regulated in mRNA levels after incubation at 0 degrees
      C for 36 and 72 h. To further elucidate protein function, we disrupted the
      PpCDC48II gene by transforming P. patens with the corresponding linear genomic
      sequences. When treated to the same freezing stress, it was found that PpCDC48II
      knockout plants were less resistant to freezing treatment than wild type after
      acclimation. This suggested that PpCDC48II was an essential gene for low
      temperature-induced freezing tolerance in P. patens cells.

PMID- 22415687
TI  - Development of a colorimetric assay for rapid quantitative measurement of
      clavulanic acid in microbial samples.
AB  - We developed a colorimetric assay to quantify clavulanic acid (CA) in culture
      broth of Streptomyces clavuligerus, to facilitate screening of a large number of
      S. clavuligerus mutants. The assay is based on a beta-lactamase-catalyzed
      reaction, in which the yellow substrate nitrocefin (lambda (max)=390 nm) is
      converted to a red product (lambda (max)=486 nm). Since CA can irreversibly
      inhibit beta-lactamase activity, the level of CA in a sample can be measured as a
      function of the A (390)/A (486) ratio in the assay mixture. The sensitivity and
      detection window of the assay were determined to be 50 MUg L(-1) and 50 MUg L(-1)
      to 10 mg L(-1), respectively. The reliability of the assay was confirmed by
      comparing assay results with those obtained by HPLC. The assay was used to screen
      a pool of 65 S. clavuligerus mutants and was reliable for identifying CA over
      producing mutants. Therefore, the assay saves time and labor in large-scale
      mutant screening and evaluation tasks. The detection window and the reliability
      of this assay are markedly better than those of previously reported CA assays.
      This assay method is suitable for high throughput screening of microbial samples
      and allows direct visual observation of CA levels on agar plates.

PMID- 22415688
TI  - Screening for differentially expressed genes in Anoectochilus roxburghii
      (Orchidaceae) during symbiosis with the mycorrhizal fungus Epulorhiza sp.
AB  - Mycorrhizal fungi promote the growth and development of plants, including
      medicinal plants. The mechanisms by which this growth promotion occurs are of
      theoretical interest and practical importance to agriculture. Here, an endophytic
      fungus (AR-18) was isolated from roots of the orchid Anoectochilus roxburghii
      growing in the wild, and identified as Epulorhiza sp. Tissue-cultured seedlings
      of A. roxburghii were inoculated with AR-18 and co-cultured for 60 d. Endotrophic
      mycorrhiza formed and the growth of A. roxburghii was markedly promoted by the
      fungus. To identify genes in A. roxburghii that were differentially expressed
      during the symbiosis with AR-18, we used the differential display reverse
      transcription polymerase chain reaction (DDRT-PCR) method to compare the
      transcriptomes between seedlings inoculated with the fungus and control
      seedlings. We amplified 52 DDRT-PCR bands using 15 primer combinations of three
      anchor primers and five arbitrary primers, and nine bands were re-amplified by
      double primers. Reverse Northern blot analyses were used to further screen the
      bands. Five clones were up-regulated in the symbiotic interaction, including
      genes encoding a uracil phosphoribosyltransferase (UPRTs; EC 2.4.2.9) and a
      hypothetical protein. One gene encoding an amino acid transmembrane transporter
      was down-regulated, and one gene encoding a tRNA-Lys (trnK) and a maturase K
      (matK) pseudogene were expressed only in the inoculated seedlings. The possible
      roles of the above genes, especially the UPRTs and matK genes, are discussed in
      relation to the fungal interaction. This study is the first of its type in A.
      roxburghii.

PMID- 22415689
TI  - Promotion of spinosad biosynthesis by chromosomal integration of the Vitreoscilla
      hemoglobin gene in Saccharopolyspora spinosa.
AB  - To promote spinosad biosynthesis by improving the limited oxygen supply during
      high-density fermentation of Saccharopolyspora spinosa, the open reading frame of
      the Vitreoscilla hemoglobin gene was placed under the control of the promoter for
      the erythromycin resistance gene by splicing using overlapping extension PCR.
      This was cloned into the integrating vector pSET152, yielding the Vitreoscilla
      hemoglobin gene expression plasmid pSET152EVHB. This was then introduced into S.
      spinosa SP06081 by conjugal transfer, and integrated into the chromosome by site
      specific recombination at the integration site PhiC31 on pSET152EVHB. The
      resultant conjugant, S. spinosa S078-1101, was genetically stable. The
      integration was further confirmed by PCR and Southern blotting analysis. A carbon
      monoxide differential spectrum assay showed that active Vitreoscilla hemoglobin
      was successfully expressed in S. spinosa S078-1101. Fermentation results revealed
      that expression of the Vitreoscilla hemoglobin gene significantly promoted
      spinosad biosynthesis under normal oxygen and moderately oxygen-limiting
      conditions (P<0.01). These findings demonstrate that integrating expression of
      the Vitreoscilla hemoglobin gene improves oxygen uptake and is an effective means
      for the genetic improvement of S. spinosa fermentation.

PMID- 22415690
TI  - Biomechanism of adhesion in gecko setae.
AB  - The study of the adhesion of millions of setae on the toes of geckos has been
      advanced in recent years with the emergence of new technology and measurement
      methods. The theory of the mechanism of adhesion by van der Waals forces is now
      accepted and broadly understood. However, this paper presents limitations of this
      theory and gives a new hypothesis of the biomechanism of gecko adhesion. The
      findings are obtained through measurements of the magnitude of the adhesion of
      setae under three different conditions, to show the close relationship between
      adhesion and status of the setae. They are reinforced by demonstrating two setal
      structures, follicle cells and hair, the former making the setae capable of
      producing bioelectrical charges, which play an important role in attachment and
      detachment processes. It is shown that the abundant muscular tissues at the base
      of the setae cells, which are controlled by peripheral nerves, are instrumental
      in producing the foot movement involved in attachment and detachment. Our study
      will further uncover the adhesion mechanism of geckos, and provide new ideas for
      designing and fabricating synthetic setae.

PMID- 22415691
TI  - Carbon cycling of Chinese forests: from carbon storage, dynamics to models.

PMID- 22415692
TI  - [International Standards of Tuberculosis Care (ISTC)--comments from the German
      point of view].
AB  - The "International Standards for Tuberculosis Care" (ISTC) were developed by the
      World Health Organisation (WHO) and others to provide internationally agreed and,
      if possible, evidence-based standards for tuberculosis care including the care by
      private providers who are not part of national tuberculosis programmes or health
      care systems. Hence, the ISTC primarily address resource-restrained countries
      with high tuberculosis prevalence. In this article, the German translation of the
      21 standards from 2009 is presented - addressing diagnostic and therapeutic
      standards, co-infection (especially with HIV) and public-health issues. The
      accompanying comments show how these standards have to be modified for Germany
      due to the medical resources available here and country-specific characteristics
      respectively.

PMID- 22415693
TI  - [Thymoma as a rare cause of non-cardiac chest pain].

PMID- 22415694
TI  - Life defined: I do not believe that the definition of life is an enormous
      problem: we have merely been looking in the wrong place.

PMID- 22415696
TI  - Is cell fusion driven by excitation? (Comment on DOI: 10.1002/bies.201100135).

PMID- 22415699
TI  - On the choice of parameterisation and priors for the Bayesian analyses of
      Mendelian randomisation studies.
AB  - Mendelian randomisation is a form of instrumental variable analysis that
      estimates the causal effect of an intermediate phenotype or exposure on an
      outcome or disease in the presence of unobserved confounding, using a genetic
      variant as the instrument. A Bayesian approach allows current knowledge to be
      incorporated into the analysis in the form of informative prior distributions,
      and the unobserved confounder can be modelled explicitly. We consider Bayesian
      methods for Mendelian randomisation in the case where all relationships are
      linear and there are no interactions. A 'full' model in which the unobserved
      confounder is included explicitly is not completely identifiable, although the
      causal parameter can be estimated. We compare inferences from this general but
      non-identified model with a reduced parameter model that is identifiable. We show
      that, theoretically, additional information about the causal parameter can be
      obtained by using the non-identifiable full model, rather than the identifiable
      reduced model, but that this is advantageous only when realistically informative
      priors are used and when the instrument is weak or the sample size is small.
      Furthermore, we consider the impact of using 'vague' versus 'informative' priors.

PMID- 22415700
TI  - Interaction of salivary and midgut proteins of Helicoverpa armigera with soybean
      trypsin inhibitor.
AB  - Feeding of Helicoverpa armigera larvae on semi-synthetic diet containing Soybean
      trypsin inhibitor (STI) resulted in disappearance of STI sensitive protease in
      salivary and midgut protease extract. This might be due to in situ inhibition by
      dietary STI. STI was largely degraded within 1 h of incubation with total
      salivary protease (1:1). Degradation was relatively low in midgut proteases. STI
      interacting proteins were isolated from saliva and midgut extracts of larvae fed
      on STI supplemented diet using affinity column. Most of the isolated proteins
      showed caseinolytic activity in zymogram. Denovo sequencing data of seven
      different peptides selected from trypsin digested total protein showed similarity
      to chymotrypsinogen, serine protease, aminopeptidase N, peroxidase, hypothetical
      protein and muscle specific protein.

PMID- 22415701
TI  - Women with occult stress incontinence should not routinely have a mid-urethral
      sling with prolapse surgery.
AB  - The risk of postoperative stress incontinence (SI) is increased in women with
      occult stress incontinence (OSI) but the majority of patients will not develop
      troublesome SI postoperatively or need further SI surgery. This risk reported in
      current studies does not warrant a mid-urethral sling at the time of surgery for
      pelvic organ prolapse in women with OSI. However, if performed, the risks as well
      as the benefits need to be discussed with the patient.

PMID- 22415702
TI  - Electromyographic evaluation of pelvic floor muscles in pregnant and nonpregnant
      women.
AB  - INTRODUCTION AND HYPOTHESIS: We compared the maximal voluntary contraction (MVC)
      and strength of pelvic floor muscles (PFM) of pregnant and nonpregnant women
      using surface electromyography (SEMG). METHODS: Fifteen pregnant primiparous
      women and 15 nulliparous nonpregnant women were evaluated. The healthy pregnant
      women were in the third trimester of pregnancy with a single fetus and did not
      have any neuromuscular alterations. The nonpregnant women did not present with PF
      dysfunctions and, as with the pregnant women, did not have any previous
      gynecological surgeries or degenerative neuromuscular alterations. The evaluation
      methods used were digital palpation (Oxford Grading Scale, which ranges from 0 to
      5) and SEMG. In the EMG exam, MVC activity was evaluated, and the better of two
      contractions was chosen. Before the evaluation, all women received information
      about PFM localization and function and how to correctly contract PFM. RESULTS:
      In the EMG evaluation, MVC was significantly greater in the nonpregnant group
      (90.7 MUv) than in the pregnant group (30 MUv), with p < 0.001. The same results
      were observed after vaginal palpation, measured by the Oxford scale, which
      presented an average of 2.1 in the pregnant group and 4.5 in the nonpregnant
      group (p = 0.005). CONCLUSION: In comparison to nulliparous women, pregnant women
      demonstrated worse PFM function with decreased strength and electrical activity.

PMID- 22415703
TI  - Levator function and voluntary augmentation of maximum urethral closure pressure.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of the study was to test whether women with
      symptoms of pelvic floor dysfunction can augment maximum urethral closure
      pressure (MUCP) with a pelvic floor muscle contraction (PFMC) and whether
      augmentation is associated with structure and function of the levator ani muscle.
      METHODS: Between January and December 2009, 300 women attended a tertiary
      referral service for multichannel urodynamic testing and 4D pelvic floor
      ultrasound. The MUCP was obtained with a perfused fluid-filled catheter.
      Augmented MUCPs were obtained during directed PFMC. Levator contraction strength
      was assessed digitally, using the Modified Oxford Grading (MOS). Levator
      integrity was determined using tomographic ultrasound, and we also measured
      dimensions of the levator hiatus at rest and on PFMC, blinded against all
      clinical data. RESULTS: The MUCP was measured at a mean of 36 cm H(2)O (range 2
      111). Augmented MUCP was 42 cm H(2)O on average (4-125). Of those who attempted
      augmentation (n = 275), 80 produced a reduction in MUCP and were excluded,
      leaving 195. There was a significant correlation between MOS and augmentation (r
      = 0.24, P = 0.001). Women with an intact levator muscle were able to augment more
      effectively (P = 0.038). CONCLUSIONS: Urethral closure pressure can be augmented
      voluntarily by symptomatic patients, on average by about 20 %. The degree of
      augmentation is positively associated with levator contractility as measured by
      digital palpation and negatively with levator avulsion.

PMID- 22415704
TI  - Vitamin D status: a review with implications for the pelvic floor.
AB  - Vitamin D is a micronutrient vital in calcium homeostasis and musculoskeletal
      function. Vitamin D insufficiency is a common variant of vitamin D deficiency
      that shows clinical signs of rickets and osteomalacia. The clinical significance
      of vitamin D insufficiency is being explored in several medical conditions.
      However, the most robust work suggests a role in musculoskeletal disease. The
      pelvic floor is a unique part of the body and the function of which is dependent
      on interrelationships between muscle, nerve, connective tissue, and bone. Pelvic
      floor disorders result when these relationships are disrupted. This paper reviews
      current knowledge regarding vitamin D nutritional status, the importance of
      vitamin D in muscle function, and how insufficient or deficient vitamin D levels
      may play a role in the function of the female pelvic floor.

PMID- 22415705
TI  - Treatment of focal dystonia.
AB  - OPINION STATEMENT: Dystonia is characterized by repetitive twisting movements or
      abnormal postures due to involuntary muscle activity. When limited to a single
      body region it is called focal dystonia. Examples of focal dystonia include
      cervical dystonia (neck), blepharospasm (eyes), oromandibular dystonia, focal
      limb dystonia, and spasmodic dysphonia, which are discussed here. Once the
      diagnosis is established, the therapeutic plan is discussed with the patients.
      They are informed that there is no cure for dystonia and treatment is
      symptomatic. The main therapeutic option for treating focal dystonias is
      botulinum toxin (BoNT). There have been several attempts to characterize the
      procedure, the type of toxin, dosage, techniques, and combination with physical
      measures in each of the focal dystonia forms. The general treatment principles
      are similar. The affected muscles are injected at muscle sites based on evidence
      and experience using standard dosages based on the type of toxin used. The
      injections are repeated after 3 to 6 months based on the individual response
      duration. In the uncommon event of nonresponse with BoNT, the dose and site are
      reassessed. Oral drug treatment could be considered as an additional option. Once
      the condition is thought to be medically refractory, the opinion from the deep
      brain stimulation (DBS) team for the suitability of the patient for DBS is taken.
      The successful use of DBS in cervical dystonia has led to increased acceptance
      for trial in other forms of focal dystonias. DBS surgery in focal dystonias other
      than cervical is, however, still experimental. The patients may be offered the
      surgery with adequate explanation of the risks and benefits. Patient education
      and directing the patients towards dystonia support groups and relevant websites
      that provide scientific information may be useful for long-term compliance and
      benefit.

PMID- 22415707
TI  - Congenital lobar emphysema: the role of multislice computed tomography with
      virtual bronchoscopy in the differential diagnosis with bronchial foreign bodies.

PMID- 22415706
TI  - NBI flexible laryngoscopy targeted tissue sampling in head and neck cancer
      patients with difficult airways.
AB  - Direct suspension laryngoscopic biopsy of neoplasms in larynx, oropharynx, and
      hypopharynx was an arduous procedure in patients with a history of head and neck
      cancer and difficult airways. This preliminary study was aimed to report the
      efficacy and safety of a narrow band imaging-guided biopsy of this category by
      flexible laryngoscopy. This is a retrospective chart review study conducted in
      setting of tertiary referral centre. Nineteen consecutive head and neck cancer
      patients with difficulty in general anesthesia and rigid endoscopic approach due
      to trismus, craniofacial deformities, and/or limited neck extension after cancer
      therapy were referred for endoscopic biopsy of their suspicious lesions in
      larynx, hypopharynx, or parts of oropharynx. Following topical anesthesia, a
      flexible laryngoscope was introduced through the nose into the pharynx. Under
      narrow band imaging magnified view, the specified tumor foci were biopsied in an
      office-based setting. All of the lesions were reached and biopsied to obtain
      sufficient tissue samples. The procedure took <20 min in every case. Twelve of
      the 19 pathologic examinations disclosed the malignancies at the first biopsy,
      and another underwent a second biopsy to prove cancer recurrence. The other six
      patients with benign lesions received further follow-up for at least 6 months and
      showed no recurrence. There were no complications associated with the technique.
      This study introduced that flexible laryngoscopy with narrow band imaging has the
      advantages of nimbleness, precision, and minimal morbidity. This combined
      technique may be a safe and promising method for tissue sampling of suspicious
      recurrence in head and neck cancer patients with difficult airways.

PMID- 22415708
TI  - Insurance and inpatient care: differences in length of stay and costs between
      surgically treated cancer patients.
AB  - BACKGROUND: Early research demonstrated that patients' length-of-stay and
      inpatient costs varied according to their health insurance status. The authors of
      the current report studied a population-based sample of privately insured,
      Medicaid-insured, and uninsured inpatients ages 21 to 64 years who underwent
      surgical resection for either nonsmall cell lung cancer (NSCLC) (n = 781) or
      colorectal cancer (CRC) (n = 8190) or who underwent mastectomy (n = 6201) to
      compare length of stay and inpatient costs by insurance status. METHODS: Data for
      this study were derived from all civilian, acute-care hospitals in Virginia from
      1999 to 2005. Hierarchical generalized linear models were used to estimate the
      relation between the explanatory variables and lengths of stay and costs. All
      analyses controlled for patient characteristics and hospital random effects.
      RESULTS: Medicaid-insured patients with NSCLC had longer lengths of stay (39% or
      2.64 days longer) and higher inpatient costs (20% or $2479 higher costs).
      Uninsured and Medicaid-insured patients with CRC had longer lengths of stay and
      higher inpatient costs. In contrast, uninsured patients with breast cancer had
      11% shorter lengths of stay and 12% lower inpatient costs than privately insured
      patients. Medicaid-insured patients had 10% lower inpatient costs than privately
      insured patients. Differences were no longer statistically significant when
      reconstruction was added to the models. CONCLUSIONS: Health insurance affected
      the need for health care and the amount of health care received. Uninsured and
      Medicaid-insured patients with lung cancer and colon cancer who underwent
      resection had longer lengths of stay and higher inpatient costs than privately
      insured patients, but they had shorter lengths of stay when reconstruction was
      not provided. Among the patients with breast cancer, patients and/or providers
      economized on discretionary procedures.

PMID- 22415709
TI  - The over-expression of cell migratory genes in alveolar rhabdomyosarcoma could
      contribute to metastatic spread.
AB  - Alveolar (ARMS) and Embryonal (ERMS) rhabdomyosarcoma differ in their response to
      current treatments. The ARMS subtype has a less favourable prognosis and often
      presents with widespread metastases, while the less metastatic ERMS has a 5 year
      survival rate of more than 80 %. In this study we investigate gene expression
      differences that could contribute to the high frequency of metastasis in ARMS.
      Microarray analysis identified significant differences in DNA repair, cell cycle
      and cell migration between the two RMS subtypes. Two genes up regulated in ARMS
      and involved in cell migration; the engulfment and cell motility gene 1 (ELMO1)
      and NEL-like 1 gene (NELL1) were selected for further investigation. Over
      expression of ELMO1 significantly increased cell invasion from 24.70 +/- 7% to 93
      +/- 5.4% in primary myoblasts and from 29.43 +/- 2.1% to 87.33 +/- 4.1% in the
      ERMS cell line RD. siRNA knockout of ELMO1 in the ARMS cell line RH30
      significantly reduced cell invasion from 88.2 +/- 3.8% to 35.2 +/- 2.5%. Over
      expression of NELL1 significantly increased myoblast invasion from 23.6 +/- 6.9%
      to 100 +/- 0.1%, but had no effect on invasion of the ERMS cell line RD. These
      findings suggest that ELMO1 may play a key role in ARMS metastasis. NELL1
      increased invasion in primary myoblasts, but other factors required for it to
      enhance motility were not present in the RD ERMS cell line. Impairing ELMO1
      function by pharmacological or siRNA knockdown could be a highly effective
      approach to reduce the metastatic spread of RMS.

PMID- 22415710
TI  - Inhibitory effect of non-anticoagulant heparin (S-NACH) on pancreatic cancer cell
      adhesion and metastasis in human umbilical cord vessel segment and in mouse
      model.
AB  - Metastasis is the most devastating aspect of cancer and it is the main cause of
      morbidity and mortality in cancer patients. Tumor cell adhesion to the vascular
      endothelial cell lining is an important step in metastatic progression and is
      prompted by platelets. Mucin 1 is over-expressed and aberrantly glycosylated in
      more than 60% of pancreatic ductal adeno-carcinomas, which mediate adhesion of
      pancreatic cancer cells to platelets via P-selectin. The anticoagulant low
      molecular weight heparins (LMWHs), which are commonly used in venous
      Thromboprophylaxis and treatment, appear to have an effect on cancer survival.
      The aim of this study is to investigate the effect of platelets on human
      pancreatic cancer MPanc96 cell adhesion to the endothelial cell vessel wall, and
      to examine the effect of heparin derivatives on MPanc96 adhesion using a novel,
      in vitro model of human umbilical cord vein. The modified heparin S-NACH
      (sulfated non-anticoagulant heparin), which is devoid of antithrombin (AT)
      binding and devoid of inhibition of systemic AT-dependent coagulation factors
      such as factor Xa and IIa, and the LMWH tinzaparin both potently reduced adhesion
      and invasion of fluorescence-labeled MPanc96 cancer cells to the endothelial
      layer of umbilical cord vein in a dose-dependent manner. S-NACH effectively
      inhibited P-selectin mediated MPanc96 cell adhesion, and inhibited cell adhesion
      and invasion similar to tinzaparin, indicating that systemic anticoagulation is
      not a necessary component for heparin attenuation of cancer cell adhesion,
      invasion, and metastasis. Also, S-NACH and tinzaparin versus unfractionated
      heparin, heparin derivatives enoxaparin, deltaparin, fraxiparin, and fondaparinux
      were evaluated for their effect on platelet-cancer cell adhesion. An in vivo anti
      metastatic S-NACH-treated nude mouse model of MPanc96 pancreatic cancer cell
      metastasis demonstrated potent anti-metastasis efficacy as evidenced by IVIS
      imaging and histological staining.

PMID- 22415711
TI  - Water flow enhancement in hydrophilic nanochannels.
AB  - All published reports on fluid flow enhancement and water slippage are associated
      with hydrophobic surfaces, such as carbon nanotubes. Here, we investigate water
      flow in hydrophilic alumina nanochannels with diameters ranging from 20 nm to 100
      nm. For the smallest channels tested, the water permeability is more than double
      than the theoretical prediction using the Hagen-Poiseuille equation. Though such
      an enhancement is significantly smaller than what has been measured in carbon
      nanotubes, it clearly shows that flow enhancement and water slippage occurs on
      hydrophilic surfaces as well, contrary to existing theoretical models. To the
      authors' knowledge, it is the first experimental demonstration of water slippage
      on hydrophilic surfaces. The results show the dependence of the flow enhancement
      on the surface chemistry, diameter and length of the nanochannel.

PMID- 22415712
TI  - Synthesis, characterization, and biological-pharmacological evaluation of new
      phosphazenes bearing dioxybiphenyl and schiff base groups.
AB  - A new spirocyclophosphazene, 2,2-bis(2-formylphenoxy)-4,4,6,6-bis[spiro(2',2"
      dioxy-1'-1"-biphenylyl)]cyclotriphosphazene (3), was obtained from the reaction
      of 2,2-dichloro-4,4,6,6-bis[spiro(2',2"-dioxy-1'-1"
      biphenylyl)]cyclotriphosphazene (2) with 2-hydroxybenzaldehyde. New phosphazene
      derivatives bearing Schiff base and dioxybiphenyl groups have been synthesized by
      the reactions of 3 with different amines. The structures of the compounds were
      defined by elemental analysis, IR, (1) H, (13) C, and (31) P NMR spectroscopy.
      All the synthesized compounds were screened for their antibacterial activity
      against both types of Gram-negative and Gram-positive bacteria. The most potent
      antibacterial compound of this series was compound 12 which has the low MIC value
      of 3.75-0.9375 ug/mL. Both minimal inhibitory concentrations (MIC) and inhibition
      zones were determined in order to monitor the efficacy of the synthesized
      compounds. New compounds were also screened for anticonvulsant, CNS depressant,
      and sedative-hypnotic activity. After i.p. injection to mice at doses of 30, 100,
      and 300 mg/kg body weight phosphazenes were examined in the maximal electroshock
      induced seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure
      models in mice. The neurotoxicity was assessed using the rotorod method.
      Compounds 4, 5, and 11 were found to be active in both MES screen and scPTZ
      screen at 0.5 h. All except 12 showed more than 44% decrease in locomotor
      activity after 1 h of compound administration via actophotometer screen. CNS
      depressant activity screened with the help of the forced swim method resulted in
      some potent compounds. Except for 7 and 12 other tested compounds were found to
      exhibit potent CNS depressants activity as indicated by increased immobility
      time.

PMID- 22415713
TI  - [Underdiagnosed disco-ligamentous lesion in the cervical spine of a paraglider].
AB  - INTRODUCTION: Paragliding is an increasingly popular airborne sport with numerous
      associated injuries. We here describe the case of an experienced paraglider who,
      after a fall from 15 meters, presented with an initially underdiagnosed disco
      ligamentous lesion of the cervical spine. PATIENT AND METHOD: We report on a 51
      year-old male paraglider, who was referred to our hospital four days after a fall
      from 15 meters. Initial treatment was performed in a regional hospital. The
      performed clinical and radiological examinations including computerized
      tomography showed, besides a fracture of the radius, no further abnormalities.
      RESULTS: The patient was discharged home four days after injury. Due to
      persistent pain in the cervical spine and parasthesia, the patient was referred
      to the practicing orthopaedic surgeon. The performed MRI and CT including the
      sagittal and coronal planes showed a disco-ligamentous lesion of the cervical
      spine. The patient was transferred immediately to our hospital for surgical
      treatment. The initial existing neurological symptoms resolved postoperatively
      and the patient was discharged home in a well condition. DISCUSSION: Injuries of
      the cervical are extremely rare in paragliders. Nevertheless, this case
      underscores the importance of adequate clinical and radiological examinations. We
      report the case of our patient to increase awareness among physicians and
      training staff working in emergency rooms.

PMID- 22415714
TI  - [Isolated rupture of the distal tendon of the biceps femoris muscle in a sport
      climber: an uncommon injury].
AB  - An isolated rupture of the distal tendon of the biceps femoris muscle without a
      direct trauma is an extremely rare injury. To date only a few case reports have
      been described in the literature. For sport climbers such an injury has never
      been described before. We report about a 41-year-old male sport climber
      complaining of such an injury after indoor rock-climbing. Unlike the previously
      described reports, the rupture occured during a phase of maximum static tension,
      without acceleration or movement of the knee joint. History and clinical
      characteristics, sonography and magnetic resonance imaging confirm the diagnosis
      and should always be performed to exclude other injuries. Early operative
      treatment with anatomic refixation of the ruptured tendon is necessary to restore
      function, although there are differences in the type of postoperative treatment.

PMID- 22415715
TI  - Imaging measures predict progression in progressive supranuclear palsy.
AB  - OBJECTIVE: The aim of this work was to determine whether the progressive
      supranuclear palsy rating scale, a measure of disease severity, is associated
      with neuroanatomical changes in progressive supranuclear palsy. METHODS: We
      recruited 22 subjects with probable progressive supranuclear palsy who completed
      the progressive supranuclear palsy rating scale at 2 time points. All subjects
      had magnetic resonance imaging and diffusion tensor imaging. Associations were
      assessed between whole brain volume, ventricular volume, midbrain area and
      superior cerebellar peduncle fractional anisotropy, and baseline/change of the
      progressive supranuclear palsy rating scale. RESULTS: Superior cerebellar
      peduncle fractional anisotropy correlated with the total score and gait/midline
      subscore of the progressive supranuclear palsy rating scale. Whole brain volume,
      midbrain area, and disease duration predicted subsequent change over time in the
      gait/midline subscore of the progressive supranuclear palsy rating scale.
      CONCLUSIONS: Imaging measures could be useful to help predict clinical
      progression in subjects with progressive supranuclear palsy.

PMID- 22415717
TI  - The psychology of LUTS: ICI-RS 2011.
AB  - INTRODUCTION: There is undoubtedly a link between lower urinary tract and
      psychological symptoms. The association is likely to be multifactorial, but
      whether psychological symptoms are causal or coincidental remains unknown.
      METHODS: This paper is a result of a think tank session conducted at the ICI-RS
      meeting 2011 in Bristol and a PubMed search on the subject of psychology and
      LUTS. RESULTS: Recent population studies have shown that LUTS are prevalent and
      that psychological morbidity is related to severity of LUTS. Evidence suggests
      that the psychological status of patients plays a significant role in their
      symptoms perception. Animal studies have shown the importance of programming and
      emotional stress on subsequent psychological problems. The link between early
      events in childhood and resulting LUTS in later life remains uncertain. The
      possibility that for some patients urinary symptoms could be part of a somatizing
      process requires further consideration. The possibility that patients' symptoms
      could be part of a somatization process needs further consideration.
      Neuroendocrine and neuroimaging studies suggest pathways that may link
      psychological and lower urinary tract functioning from early life, opening new
      avenues to better understand the treatment of both symptom groups. CONCLUSION:
      Whilst psychological morbidity will result from any distressing chronic medical
      condition the possibility of causation, and or maintenance of LUTS through
      psychological causes requires further research. It is important to recognize that
      amongst our younger and older patients suffering with LUTS a significant
      psychological component exists. Failure to address this may lead to incomplete
      assessment and consequently inadequate treatment.

PMID- 22415718
TI  - A role for WNT/beta-catenin signaling in the neural mechanisms of behavior.
AB  - Wnt signaling pathways play a role in a variety of cellular processes including
      development, cell proliferation, cell fate, and motility. The Wnt/beta-catenin
      pathway is among the most studied of the Wnt pathways and is highly conserved
      throughout evolution. Recent in vitro and slice physiology experiments have shown
      that this pathway also functions in synaptic transmission and activity-dependent
      synaptic plasticity. Since it has now been shown that many components of this
      signaling pathway are found in the adult brain, Wnt/beta-catenin signaling may be
      important for maintaining and protecting neural connections throughout the
      lifespan. Here we summarize the role of Wnt/beta-catenin signaling in the
      postnatal brain and discuss recent studies suggesting that deregulated Wnt
      signaling can result in altered behavior and cognitive disorders.

PMID- 22415719
TI  - Nuclear translocation of beta-catenin is essential for glioma cell survival.
AB  - Identification of molecular pathways that are essential for cancer cell survival
      is vital for understanding the underlying biology, as well as to design effective
      cancer therapeutics. beta-catenin, a multifunctional oncogenic protein,
      participates in cell development. Its multifaceted functions primarily lie to the
      subcellular distribution. The present study demonstrated that beta-catenin
      accumulated in the nucleus to a greater extent in high-grade gliomas compared
      with low-grade gliomas. In addition, nuclear localization correlated with a worse
      prognosis for patients, as determined by immunohistochemical analysis of 74
      glioma samples. Nuclear expression of beta-catenin was down-regulated in LN229
      and U87 glioma cells by a small molecule inhibitor of beta-catenin/TCF4
      signaling, demonstrating strongly inhibited beta-catenin/TCF4 transcriptional
      activity and STAT3 luciferase activity, as well as decreased mRNA and protein
      levels of nuclear beta-catenin, TCF4, EGFR, AKT1, AKT2 and STAT3. Furthermore,
      repressed nuclear translocation of beta-catenin resulted in inhibition of
      proliferation and invasiveness, and also induced apoptosis of glioma cells.
      Similar results were also observed in vivo; intratumoral injection of such small
      molecule inhibitor downregulated expression of nuclear beta-catenin, TCF4, and
      components of the EGFR pathway, and also delayed tumor growth in nude mice
      harboring subcutaneous U87 xenografts. Results from the present study provided
      evidence that nuclear accumulation of beta-catenin participated in malignant
      progression of gliomas and implicated poor prognosis, highlighting it as a
      potential therapeutic target for gliomas.

PMID- 22415720
TI  - Functional imaging and the cerebellum: recent developments and challenges.
      Editorial.
AB  - Recent neuroimaging developments allow a better in vivo characterization of the
      structural and functional connectivity of the human cerebellum. Ultrahigh fields,
      which considerably increase spatial resolution, enable to visualize deep
      cerebellar nuclei and cerebello-cortical sublayers. Tractography reconstructs
      afferent and efferent pathway of the cerebellum. Resting-state functional
      connectivity individualizes the prewired, parallel close-looped sensorimotor,
      cognitive, and affective networks passing through the cerebellum. These results
      are un agreement with activation maps obtained during stimulation functional
      neuroimaging or inferred from neurological deficits due to cerebellar lesions.
      Therefore, neuroimaging supports the hypothesis that cerebellum constitutes a
      general modulator involved in optimizing mental performance and computing
      internal models. However, the great challenges will remain to unravel: (1) the
      functional role of red and bulbar olivary nuclei, (2) the information processing
      in the cerebellar microcircuitry, and (3) the abstract computation performed by
      the cerebellum and shared by sensorimotor, cognitive, and affective domains.

PMID- 22415721
TI  - Correspondence of ectomycorrhizal diversity and colonisation of willows (Salix
      spp.) grown in short rotation coppice on arable sites and adjacent natural
      stands.
AB  - Willows (Salix spp.) are mycorrhizal tree species sometimes cultivated as short
      rotation coppice (SRC) on arable sites for energy purposes; they are also among
      the earliest plants colonising primary successional sites in natural stands. The
      objective of this study was to analyse the degree of colonisation and diversity
      of ectomycorrhizal (EM) communities on willows grown as SRC in arable soils and
      their adjacent natural or naturalized stands. Arable sites usually lack
      ectomycorrhizal host plants before the establishment of SRC, and adjacent natural
      or naturalized willow stands were hypothesized to be a leading source of
      ectomycorrhizal inoculum for the SRC. Three test sites including SRC stands
      (Salix viminalis, Salix dasyclados, and Salix schwerinii) and adjacent natural or
      naturalized (Salix caprea, Salix fragilis, and Salix * mollissima) stands in
      central Sweden were investigated on EM colonisation and morphotypes, and the
      fungal partners of 36 of the total 49 EM fungi morphotypes were identified using
      molecular tools. The frequency of mycorrhizas in the natural/naturalized stands
      was higher (two sites) or lower (one site) than in the corresponding cultivated
      stands. Correspondence analysis revealed that some EM taxa (e.g. Agaricales) were
      mostly associated with cultivated willows, while others (e.g. Thelephorales) were
      mostly found in natural/naturalized stands. In conclusion, we found strong
      effects of sites and willow genotype on EM fungi formation, but poor
      correspondence between the EM fungi abundance and diversity in SRC and their
      adjacent natural/naturalized stands. The underlying mechanism might be selective
      promotion of some EM fungi species by more effective spore dispersal.

PMID- 22415722
TI  - Endoscopic treatment of Haglund's syndrome with a three portal technique.
AB  - PURPOSE: The purpose of our study is to make a retrospective evaluation of
      endoscopic treatment of Haglund's syndrome using a new three portal technique.
      METHODS: All 23 patients (25 heels) with a mean age of 27.7 years were evaluated
      pre-operatively and postoperatively with parallel pitch lines, the American
      Orthopaedic Foot and Ankle Society (AOFAS) score and the Ogilvie Harris score.
      RESULTS: The mean follow-up was 41 months (range, 30-59 months). There were no
      obvious complications in our study. In 22 heels, postoperative lateral
      radiographs showed the achievement of negative parallel pitch lines. The average
      AOFAS score improved from 63.3 +/- 11.9 points pre-operatively to 86.8 +/- 10.1
      points at final follow-up. There were 14 excellent results, seven good results,
      two fair results and two poor results. For the Ogilvie Harris score, there were
      15 excellent, seven good, one fair, and two poor results. CONCLUSION: An
      endoscopic procedure using the three portal technique seemed to be a safe and
      efficacious option for surgical treatment of Haglund's syndrome.

PMID- 22415723
TI  - Platinum-catalysed bisindolylation of allenes: a complementary alternative to
      gold catalysis.
AB  - Pt versus Au: Platinum-catalysed addition of nucleophiles to allenes follows a
      distinctly different pathway to the process catalysed by gold(I) complexes; the
      platinum catalyst leads to different products with indoles involving a
      bisindolylation reaction, whereas gold(I) gives allyl indoles from a single
      addition (see scheme).

PMID- 22415724
TI  - Super-resolution imaging prompts re-thinking of cell biology mechanisms: selected
      cases using stimulated emission depletion microscopy.
AB  - The use of super-resolution imaging techniques in cell biology has yielded a
      wealth of information regarding cellular elements and processes that were
      invisible to conventional imaging. Focusing on images obtained by stimulated
      emission depletion (STED) microscopy, we discuss how the new high-resolution data
      influence the ways in which we use and interpret images in cell biology. Super
      resolution images have lent support to some of our current hypotheses. But, more
      significantly, they have revealed unexpectedly complex processes that cannot be
      accounted for by the simpler models based on diffraction-limited imaging. The
      super-resolution imaging data challenge cell biologists to change their
      theoretical framework, by including, for instance, interpretations that describe
      multiple functions, functional errors or lack of function for cellular elements.
      In this context, we argue that descriptive research using super-resolution
      microscopy is now as necessary as hypothesis-driven research.

PMID- 22415725
TI  - Flagging clinical adverse experiences: reducing false discoveries without
      materially compromising power for detecting true signals.
AB  - Comparative analyses of safety/tolerability data from a typical phase III
      randomized clinical trial generate multiple p-values associated with adverse
      experiences (AEs) across several body systems. A common approach is to 'flag' any
      AE with a p-value less than or equal to 0.05, ignoring the multiplicity problem.
      Despite the fact that this approach can result in excessive false discoveries
      (false positives), many researchers avoid a multiplicity adjustment to curtail
      the risk of missing true safety signals. We propose a new flagging mechanism that
      significantly lowers the false discovery rate (FDR) without materially
      compromising the power for detecting true signals, relative to the common no
      adjustment approach. Our simple two-step procedure is an enhancement of the
      Mehrotra-Heyse-Tukey approach that leverages the natural grouping of AEs by body
      systems. We use simulations to show that, on the basis of FDR and power, our
      procedure is an attractive alternative to the following: (i) the no-adjustment
      approach; (ii) a one-step FDR approach that ignores the grouping of AEs by body
      systems; and (iii) a recently proposed two-step FDR approach for much larger
      scale settings such as genome-wide association studies. We use three clinical
      trial examples for illustration.

PMID- 22415726
TI  - Hip injuries in the overhead athlete.
AB  - BACKGROUND: The overhead athlete is at risk for shoulder and elbow injuries.
      However, the mechanics associated with overhead sports also place athletes at
      risk for hip injuries. Advancements in hip arthroscopy have identified
      femoroacetabular impingement (FAI) and instability as potential contributors to
      labral and chondral pathology in this athletic population. QUESTIONS/PURPOSES: We
      therefore determined whether hip function improves after arthroscopic treatment
      of FAI in overhead athletes and the rate at which overhead athletes returned to
      preinjury level of play. METHODS: We retrospectively identified high-level
      baseball and lacrosse players (varsity high school, collegiate, and professional)
      who underwent arthroscopic treatment for FAI. Thirty-four athletes with an
      average age of 21.4 years met study criteria. There were 16 baseball players and
      18 lacrosse players. All patients completed modified Harris hip scores and were
      assessed for ability to return to preinjury level of play. The minimum followup
      was 12 months (average, 25 months; range 12-41 months). RESULTS: Mean modified
      Harris hip scores improved from 70 to 92. Thirty-three of 34 patients were able
      to return to preinjury level of sports participation. CONCLUSIONS: Arthroscopic
      management of hip injuries in the high-level overhead throwing athlete can result
      in a high rate of return to play. Mechanical overload of the hip from impingement
      and secondary instability can have a substantial effect on hip function and may
      be the cause of deterioration in athletic performance in some cases. LEVEL OF
      EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 22415728
TI  - Retrieval studies in orthopaedic surgery: Editorial comment: Learning every
      implant's story.

PMID- 22415727
TI  - Anti-TGF-beta antibody combined with dendritic cells produce antitumor effects in
      osteosarcoma.
AB  - BACKGROUND: We previously reported the combination of tumor cryotreatment with
      dendritic cells to promote antitumor immunity. The effect of the combination
      treatment with dendritic cells and antitransforming growth factor-beta (anti-TGF
      beta) antibody on the elimination of regulatory T cells and the inhibition of
      tumor growth was investigated. QUESTIONS/PURPOSES: The effects of the combination
      treatment with dendritic cells and anti-TGF-beta antibody on the enhancement of
      systemic immune responses and inhibition of metastatic tumor growth were
      investigated in a murine osteosarcoma (LM8) model. MATERIALS AND METHODS: To
      evaluate activation of the immune response, we established the following three
      groups of C3H mice (60 mice total): (1) excision only; (2) tumor excision and
      administration of anti-TGF-beta antibody; and (3) tumor excision and
      administration of dendritic cells exposed to cryotreated tumor lysates with anti
      TGF-beta antibody. RESULTS: The mice that received dendritic cells exposed to
      cryotreated tumor lysates with anti-TGF-beta antibody showed increased numbers of
      CD8(+) T lymphocytes, reduced regulatory T lymphocytes in the metastatic lesion,
      and inhibition of metastatic growth. The combined therapy group showed reduced
      numbers of regulatory T lymphocytes in the spleen and high serum interferon gamma
      level. CONCLUSIONS: The control of the inhibitory condition induced by regulatory
      T cells is important to improve the suppression of the cytotoxic lymphocytes.
      Combining dendritic cells with anti-TGF-beta antibody enhanced the systemic
      immune response. CLINICAL RELEVANCE: We suggest that our immunotherapy could be
      developed further to improve the treatment of osteosarcoma.

PMID- 22415729
TI  - Sovereign immunity: Principles and application in medical malpractice.
AB  - BACKGROUND: Tort law seeks accountability when parties engage in negligent
      conduct, and aims to compensate the victims of such conduct. An exception to this
      general rule governing medical negligence is the doctrine of sovereign immunity.
      Historically, individuals acting under the authority of the government or other
      sovereign entity had almost complete protection against tort liability.
      QUESTIONS/PURPOSES: This article addressed the following: (1) the development of
      sovereign immunity in law, (2) the lasting impact of the Federal Tort Claims Act
      on sovereign immunity, and (3) the contemporary application of sovereign immunity
      to medical malpractice, using case examples from Virginia and Florida. METHODS: I
      performed an Internet search to identify sources that addressed the concept of
      sovereign immunity, followed by a focused search for relevant articles in PubMed
      and LexisNexis, literature databases for medical and legal professionals,
      respectively. RESULTS: Historically, sovereign liability conferred absolute
      immunity from lawsuits in favor of the sovereign (ie, the government). Practical
      considerations in our democratic system have contributed to an evolution of this
      doctrine. CONCLUSIONS: Understanding sovereign immunity and its contemporary
      application are of value for any physician interested in the debate concerning
      medical malpractice in the United States. Under certain circumstances, physicians
      working as employees of the federal or state government may be protected against
      individual liability if the government is substituted as the defendant.

PMID- 22415730
TI  - Current approaches in cerebral palsy, a focus on gait problems: editorial
      comment.

PMID- 22415731
TI  - Identification of a truncation mutation of acylglycerol kinase (AGK) gene in a
      novel autosomal recessive cataract locus.
AB  - Hereditary forms of cataract are genetically heterogeneous. Mutations in
      crystallin genes account for most Mendelian forms, but identification of other
      cataract genes has provided insights into additional molecular mechanisms that
      control lens transparency. In a multiplex consanguineous family with isolated
      congenital cataract, we identified a novel autosomal recessive cataract locus on
      7q33-q36.1. Exome sequencing revealed a splice-site mutation in AGK, encoding
      acylglycerol kinase, which we confirm led to aberrant splicing and predicted
      premature truncation. This is the first mutation in this lipid metabolism gene to
      be implicated in the development of isolated cataract, although it remains to be
      seen if the mechanism involves perturbation of lenticular lipid composition or
      aberrant signaling during lens morphogenesis.

PMID- 22415732
TI  - Comparing nouns and verbs in a lexical task.
AB  - We analyzed the differential processing of nouns and verbs in a lexical decision
      task. Moderate and high-frequency nouns and verbs were compared. The
      characteristics of our material were specified at the formal level (number of
      letters and syllables, number of homographs, orthographic neighbors, frequency
      and age of acquisition), and at the semantic level (imagery, number and strength
      of associations, number of meanings, context dependency). A regression analysis
      indicated a classical frequency effect and a word-type effect, with latencies for
      verbs being slower than for nouns. The regression analysis did not permit the
      conclusion that semantic effects were involved (particularly imageability).
      Nevertheless, the semantic opposition between nouns as prototypical
      representations of objects, and verbs as prototypical representation of actions
      was not tested in this experiment and remains a good candidate explanation of the
      response time discrepancies between verbs and nouns.

PMID- 22415733
TI  - Activating situation schemas: the effects of multiple thematic roles on related
      verbs in a continuous priming paradigm.
AB  - Extensive evidence has shown that presentation of a word (target) following a
      related word (prime) results in faster reaction times compared to unrelated
      words. Two primes preceding a target have been used to examine the effects of
      multiple influences on a target. Several studies have observed greater, or
      additive, priming effects of multiple related primes compared to single related
      primes. The present study aims to eliminate attentional factors that may have
      contributed to findings in previous studies that used explicitly presented primes
      and targets. Thus, a continuous priming paradigm where targets are unknown to
      participants is used with noun-noun-verb triads filling agent, patient, and
      action roles in situation schemas (tourist, car, rent). Results replicate priming
      of single nouns preceding related verbs but do not suggest an additive effect for
      two nouns versus one. The absence of additive priming suggests that attentional
      processes may have been a factor in previous research.

PMID- 22415734
TI  - A note from history: landmarks in history of cancer, part 4.
AB  - In the second half of the 19th century, most cancer patients were cared for by
      surgeons who exerted ascesis and limited their operations to 1 or 2 specific
      areas. To assist surgeons and other physicians in caring for their patients,
      pathologists described newly discovered entities, refined the microscopic
      classification of tumors, and introduced the grading of cancers. The discoveries
      of Rontgen and the Curies revolutionized the diagnosis and treatment of cancers.
      The search for the cause of cancers extended to infectious organisms, chemicals,
      and radioactive materials. The 50 years covered in this review formed the
      groundwork for the coordinated, specialized care of cancer patients at
      institutions dedicated to render the most promising treatment.

PMID- 22415736
TI  - Effect of addition of 'carrier' DNA during transient protein expression in
      suspension CHO culture.
AB  - Transient protein expression using polyethyleneimine as a transfection agent is
      useful for the rapid production of small amounts of recombinant proteins. It is
      known that an increase in extracellular DNA concentration during transfection can
      lead to a nonlinear increase in intracellular DNA concentration. We present an
      approach that hypothesizes that this nonlinearity can be used to  decrease the
      amount of plasmid required for productive transfections. Through addition of non
      coding 'carrier' DNA to increase total DNA concentration during transfection, we
      report a statistically significant increase in protein (IgG) expression per unit
      plasmid used for transfection. This approach could be useful to increase protein
      yields for large scale transfections under conditions where plasmid availability
      is limited.

PMID- 22415737
TI  - Effect of the distance between adherent mesenchymal stem cell and the focus of
      irradiation of femtosecond laser on cell replication capacity.
AB  - The effect of femtosecond laser irradiation on adherent mesenchymal stem cell was
      investigated with the aim to develop a novel noninvasive cell purification
      system. A single mesenchymal stem cell was irradiated with a femtosecond laser on
      the center of the cell using several energy values and the cell lost its
      replication capacity with one time irradiation with an energy of 2.0 MUJ. Besides
      at a neighbor point in the major axis, when irradiated in the minor axis at a
      distance shorter than 10 MUm, the cell stopped its replication capacity. The
      accumulation effect of cell damage caused by multiple laser shots at a neighbor
      point in the minor axis was correlated with the critical distance at which the
      cell lost its replication capacity. Finally, a novel equation of laser cell
      damage as a function of laser pulse energy and laser shot number is proposed.

PMID- 22415738
TI  - Dynamic photo-control of kinesin on a photoisomerizable monolayer--hydrolysis
      rate of ATP and motility of microtubules depending on the terminal group.
AB  - The reversibly and repeatedly altered gliding motility of microtubules driven by
      kinesin on the photoresponsive monolayer surface is studied. It was confirmed
      that an azobenzene monolayer surface needs to have free amino terminal groups for
      the successful dynamic control of the motility of microtubule. The surface of the
      azobenzene monolayer with terminal amino groups can dynamically control the ATP
      hydrolysis activity of kinesin which resulted in the change in motility of the
      microtubules.

PMID- 22415739
TI  - Automatic segmentation of carotid B-mode images using fuzzy classification.
AB  - This paper presents a new method for the automatic segmentation of the common
      carotid artery in B-mode images. This method uses the instantaneous coefficient
      of variation edge detector, fuzzy classification of edges and dynamic
      programming. Several discriminating features of the intima and adventitia
      boundaries are considered, like the edge strength, the intensity gradient
      orientation, the valley shaped intensity profile and contextual information of
      the region delimited by those boundaries. The adopted fuzzy classification of
      edges helps avoiding low-pass filtering. The method is suited to real-time
      processing and user interaction is not required. Both the near and far wall
      boundaries can be detected in arteries with plaques of different types and sizes.
      Both expert manual and automatic tracings are significantly better for the far
      wall, due to the better visibility of the intima and adventitia boundaries. The
      automatic detection of the far wall shows an accuracy similar to the manual
      detections. For this wall, the error coefficient of variation for the mean intima
      media thickness is in the range [5.6, 6.6 %] for automatic detections and in
      [6.7, 7.1 %] for manual ones. In the case of the near wall, the same coefficient
      of variation is in [11.2, 13.0 %] for automatic detections and in [5.9, 9.0 %]
      for manual detections. The mean intima-media thickness measurement errors
      observed for the far wall [Formula: see text] are among the best values reported
      for other fully automatic approaches. The application of this approach in
      clinical practice is encouraged by the results for the far wall and the short
      processing time (mean of 2.1 s per image).

PMID- 22415740
TI  - Efficient and robust estimation of blood oxygenation levels in single cerebral
      veins.
AB  - Blood oxygenation level is an important measure that can be used alongside
      functional magnetic resonance imaging data in order to obtain closer correlates
      of neuronal activation. A robust estimate of this measure has thus far not been
      demonstrated. This is mainly due to the lack of knowledge of the underlying
      parameters which influence the numerical estimates of blood oxygenation. In this
      paper, we present a systematic analysis of the estimation performance of venous
      hemoglobin oxygen saturation [Formula: see text] as a function of noise,
      physiologic and geometric parameters. Furthermore, we present a novel algorithm
      for estimating [Formula: see text] from the temporal decay of an MR signal. The
      proposed algorithm incorporates prior information about the functional dependence
      between [Formula: see text] and relaxation rates. We compare our algorithm to an
      existing method in the literature and analyze the estimation performance. We show
      that our proposed algorithm is more efficient, achieving gains in performance as
      high as 92 %. We also show how our estimation algorithm takes advantage of signal
      features that are specific to the underlying physiology and geometry. We argue
      that optimal acquisition sequences, and corresponding estimation methods, should
      take into account such features in order to obtain robust estimates of blood
      oxygenation.

PMID- 22415741
TI  - Comparative analysis of perioperative intraperitoneal chemotherapy regimen in
      appendiceal and colorectal peritoneal carcinomatosis.
AB  - BACKGROUND: Perioperative intraperitoneal chemotherapy (PIC) is delivered by
      intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and early
      postoperative intraperitoneal chemotherapy (EPIC). The relative survival benefits
      of each or both regimens are explored in this large series of patients undergoing
      cytoreduction at a single institution. METHODS: Patients with a complete (CCR0)
      or optimal (CCR1) cytoreduction who received intraperitoneal chemotherapy for
      appendiceal and colorectal peritoneal carcinomatosis were included for analysis.
      PIC regimens were delivered according to the treatment protocol. Standardized
      statistical analyses were performed. RESULTS: Of 262 patients, 98 patients (37%)
      had colorectal peritoneal carcinomatosis, 108 patients (41%) had low-grade
      pseudomyxoma peritonei and 56 patients (21%) had appendiceal peritoneal
      carcinomatosis. For pseudomyxoma peritonei, recurrence-free survival (RFS) did
      not vary with PIC regimen, 5-year survival was 86% in the HIPEC and EPIC group
      and 64% in the HIPEC or EPIC group (P = 0.070). For appendiceal peritoneal
      carcinomatosis, RFS and overall survival (OS) did not vary with PIC regimen. For
      colorectal peritoneal carcinomatosis, the median RFS was 33 months in the HIPEC
      and EPIC group, 19 months in the HIPEC alone group and 20 months in the EPIC
      alone group (P = 0.046). OS did not vary with PIC regimen. CONCLUSION: From our
      experience, without compromising the perioperative morbidity and mortality, PIC
      consisting of HIPEC and EPIC appears to be associated with potential survival
      benefits of improved OS in pseudomyxoma peritonei and RFS in colorectal
      peritoneal carcinomatosis.

PMID- 22415742
TI  - Reasons for avoidance of bevacizumab with first-line FOLFOX for advanced
      colorectal cancer.
AB  - BACKGROUND: The addition of bevacizumab to standard chemotherapy has significant
      clinical benefits in metastatic colorectal cancer. However, its use is often
      avoided due to patient condition or disease status. METHODS: Of 228 consecutive
      patients receiving first-line FOLFOX-based regimens from June 2007 to June 2009,
      96 patients (42 %) received FOLFOX alone without bevacizumab. We retrospectively
      examined the reasons why bevacizumab was not combined with FOLFOX. RESULTS: Among
      96 patients for whom the addition of bevacizumab was avoided, 73 patients (76 %)
      had bevacizumab-related contraindications including hypertension, proteinuria,
      bleeding, thromboembolic events, wound-healing complications and gastrointestinal
      perforation. Other avoidance reasons were conditions precluding the use of
      bevacizumab in 15 patients (16 %), economic problems and anxiety about adverse
      events in 8 patients (8 %), and unknown reasons in 3 patients. CONCLUSIONS:
      Bevacizumab-related contraindications were the main reason for drug avoidance,
      though economic problems and anxiety about rare but serious adverse events were
      also factors for avoidance of bevacizumab.

PMID- 22415743
TI  - First indicators of relapse in breast cancer: evaluation of the follow-up program
      at our hospital.
AB  - BACKGROUND: Guidelines for breast cancer patient follow-up have not been widely
      adopted in Japan. To assess our intensive follow-up program, we evaluated first
      relapse and its indicators in patients with breast cancer. PATIENTS: Of 964
      patients, 126 relapsed and 43 died in the median follow-up term of 45 months.
      Follow-ups were scheduled every 6-12 months for imaging and tumor marker (TM)
      evaluation. RESULTS: Of 126 relapsed patients, 30 (23.8%) had symptoms of
      relapse. First indicators of relapse in 96 asymptomatic patients were physical
      examination in 24 patients (19%); imaging, 57 patients (45.3%); and TMs, 15
      patients (11.9%). The most sensitive indicators were physical examination for
      local relapse, ultrasonography for regional lymph nodes, scintigraphy for bone,
      computed tomography for lung, and TMs for liver metastasis. During intensive
      follow-up, 43% of relapsed patients were identified by symptoms or physical
      examination. These patients had poor prognosis compare to patients identified by
      imaging or TMs in overall survival and post-relapse survival (p = 0.009 and
      0.019, respectively). In all 964 patients, the relapse rates for stage I, IIA,
      IIB, and III tumors were 7.4, 7.9, 19.9, and 43.5%, respectively. The percentage
      of first relapse detected by imaging or TMs for stage I, IIA, IIB, and III were
      4.7, 5.1, 11.8, and 19.8%, respectively. The cost of our follow-up program for 10
      years was approximately 290,000 yen per patient. CONCLUSION: A routine intensive
      follow-up program involving imaging and evaluation of TMs in all patients has low
      efficacy and high expenditure.

PMID- 22415744
TI  - Synthesis and preliminary pharmacological investigation of new N-substituted-N
      [omega-(omega-phenoxy-alkylpiperazin-1-yl)alkyl]guanidines as non-imidazole
      histamine H(3) antagonists.
AB  - Novel, potent non-imidazole histamine H(3)  receptor antagonists were prepared.
      Detailed structure-activity studies revealed that N-(4-trifluoromethylbenzyl)-N
      [4-(7-phenoxyheptylpiperazin-1-yl)butyl]guanidine (pA(2)  = 8.49 +/- 0.05), 1h,
      and N-(4-nitrobenzyl)-N-[4-(7-phenoxyheptylpiperazin-1-yl)butyl]guanidine (pA(2) 
      = 8.43 +/- 0.05), 1l, exhibit high affinity for the H(3)  histamine receptor. The
      most potent antagonists in this series, 1e, 1h, and 1l, were also in vitro tested
      as H(1)  receptor antagonists, showing weak H(1) -antagonistic activity with
      pA(2)  = 6.70 +/- 0.09, pA(2)  = 6.46 +/- 0.09, and pA(2)  = 6.65 +/- 0.11,
      respectively.

PMID- 22415745
TI  - Abnormal axillary lymph nodes on negative mammograms: causes other than breast
      cancer.
AB  - Enlargement of lymph nodes can be due to a variety of benign and malignant    
      causes. The most common malignant cause is invasive ductal carcinoma, which is   
      usually visualized with mammography. Excluding breast cancer, other causes of   
      abnormal lymph nodes that produce a negative mammogram include lymphoma,    
      metastases from other malignancies, and benign etiologies such as inflammatory   
      processes, infectious diseases, collagen vascular diseases, and miscellaneous   
      causes. In this essay, we described common causes of abnormal axillary lymph    
      nodes on negative mammograms excluding breast cancer.

PMID- 22415746
TI  - Plus ca change, plus c'est la meme chose: reflection on access to health care in
      mainstream services by people with intellectual disabilities in England.

PMID- 22415747
TI  - The mediating impact of coping style on stress perception for parents of
      individuals with intellectual disabilities.
AB  - Research reveals that parents of individuals with intellectual disabilities
      experience more stress than parents of persons of normal development. The
      majority of previous research has measured direct relationships between stress
      variables and stress perception and little attention has been given to the impact
      of mediating variables. The present study utilized an indirect pathway model to
      examine the mediating influence of coping style on the relationship between
      social support, severity of child disability, parental optimism and stress
      perception for these parents. Parents of individuals receiving mental health
      services through an agency in Southeastern Michigan participated in the study.
      Results indicated that coping style partially mediated the relationship between
      social support and stress perception for parents of individuals with intellectual
      disabilities.

PMID- 22415748
TI  - Non-verbal communication between Registered Nurses Intellectual Disability and
      people with an intellectual disability: an exploratory study of the nurse's
      experiences. Part 1.
AB  - This is the first of two articles presenting the findings of a qualitative study
      which explored the experiences of Registered Nurses Intellectual Disability
      (RNIDs) of communicating with people with an intellectual disability who
      communicate non-verbally. The article reports and critically discusses the
      findings in the context of the policy and service delivery discourses of person
      centredness, inclusion, choice and independence. Arguably, RNIDs are the
      profession who most frequently encounter people with an intellectual disability
      and communication impairment. The results suggest that the communication studied
      is both complicated and multifaceted. An overarching category of
      'familiarity/knowing the person' encompasses discrete but related themes and
      subthemes that explain the process: the RNID knowing the service-user; the
      RNID/service-user relationship; and the value of experience. People with an
      intellectual disability, their families and disability services are facing a time
      of great change, and RNIDs will have a crucial role in supporting this
      transition.

PMID- 22415750
TI  - What determines whether a patient with LUTS seeks treatment? ICI-RS 2011.
AB  - AIMS: To review the known determinants of healthcare-seeking behavior for LUTS
      and address unmet needs and future research priorities. METHODS: The PubMed
      literature was searched for currently known factors affecting treatment seeking
      for LUTS, OAB, and incontinence in men and women. RESULTS: Further to the great
      variation in rates for treatment seeking for LUTS in both men and women, several
      biomedical and psychosocial factors affecting HSB have been identified in studies
      to date. Symptom severity and bother, age, and impact on quality of life have
      consistently been identified as potent determinants of treatment seeking for
      LUTS. Race and ethnicity also play a role. Advice from others and the media,
      embarrassment, personal beliefs and attitudes towards healthcare use, and
      subjective well-being are but a few of the psychosocial determinants which may
      impact on a patient's decision to seek medical advice for LUTS. Studying the role
      of reassurance versus medical treatment, referral patterns for LUTS in various
      populations, the role of comorbidities in HSB, cultural issues, bother-associated
      parameters and psychosocial profiles in association with healthcare-seeking,
      patients' expectations, HSB in relation to health economics, and development of
      questionnaires on HSB for patients and physicians should be amongst future
      research priorities. CONCLUSIONS: Increasing research interest has helped
      identify several biomedical and psychosocial factors affecting HSB for LUTS.
      Qualitative research is needed as well as studies to address aspects of HSB, not
      only in subjects attending the available healthcare services, but even more in
      those patients who do not seek medical advice for their LUTS.

PMID- 22415749
TI  - Temporal relationships between depressive symptoms and white matter
      hyperintensities in older men and women.
AB  - OBJECTIVE: Associations between vascular disease and depression in late life,
      including increased white matter hyperintensities (WMHs), have been reported.
      Whether depression is an etiology or a consequence of vascular disease is still
      unknown. We investigated the temporal relationship between depressive symptoms
      and WMHs in older men and women. METHODS: We utilized data from 90 dementia-free
      older adults (39 women, 51 men), 57 years of age and older at baseline, from the
      neuroimaging substudy of the Baltimore Longitudinal Study of Aging. Participants
      were followed for up to 8 years. Ratings of white matter disease burden were
      available for the first, last, and at least one interim visit, and participants
      completed the Center for Epidemiologic Studies Depression Scale (CES-D) annually.
      Statistical models, performed separately in men and women, examined whether
      depressive symptoms predicted subsequent WMH ratings or WMHs predicted subsequent
      depressive symptoms. RESULTS: The total CES-D score was not associated with WMHs
      in men or women. In men, the CES-D depressed mood subscale predicted accelerating
      longitudinal increases in WMHs at older ages, but WMHs did not predict subsequent
      depressive symptoms. In women, there were no significant associations between the
      CES-D depressed mood subscale and WMHs. CONCLUSIONS: White matter disease may be
      a consequence of depressed mood in men but not in women. Intervention strategies
      for depression may slow the progression of white matter disease in older men.
      These results add to previous findings documenting sex differences in the
      correlates of depressive disorders in late life.

PMID- 22415751
TI  - Regulation of Th1/Th2 polarization by tissue inhibitor of metalloproteinase-3 via
      modulating dendritic cells.
AB  - Tissue inhibitor of metalloproteinase-3 (TIMP-3) is one of a family of proteins
      inhibiting matrix metalloproteinases, which has also been identified as a
      mediator for checking inflammation. Meanwhile, it is well known that inflammation
      causes the activation of the immune response. However, it is not clear whether
      TIMP-3 plays a role in the immune system. In the present study, we demonstrated a
      novel function of TIMP-3 in Th1/Th2 polarization through its influence on the
      antigen-presenting cells. First, TIMP-3 was found strikingly up-regulated by IL-4
      during the differentiation of human dendritic cells via the p38MAPK pathway.
      Second, the expression of costimulatory molecule-CD86 was repressed by TIMP-3.
      Besides, the induction of IL-12 in matured dendritic cells was significantly
      inhibited in a PI3K-dependent manner. Furthermore, dendritic cells matured in the
      presence of TIMP-3 could stimulate allogeneic naive T helper (Th) cells to
      display a prominent Th2 polarization. Importantly, in an autoimmune disorder
      primary immune thrombocytopenia, TIMP-3 showed a statistically positive
      correlation with IL-4 and platelet count, but a negative correlation with IFN
      gamma in patient blood samples. Collectively, these in vitro and in vivo data
      clearly suggested a novel role of TIMP-3 in Th1/Th2 balance in humans.

PMID- 22415752
TI  - Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a
      molecular classification with implications for targeted therapies.
AB  - Mounting evidence indicates that grouping of chronic lymphocytic leukemia (CLL)
      into distinct subsets with stereotyped BCRs is functionally and prognostically
      relevant. However, several issues need revisiting, including the criteria for
      identification of BCR stereotypy and its actual frequency as well as the
      identification of "CLL-biased" features in BCR Ig stereotypes. To this end, we
      examined 7596 Ig VH (IGHV-IGHD-IGHJ) sequences from 7424 CLL patients, 3 times
      the size of the largest published series, with an updated version of our purpose
      built clustering algorithm. We document that CLL may be subdivided into 2
      distinct categories: one with stereotyped and the other with nonstereotyped BCRs,
      at an approximate ratio of 1:2, and provide evidence suggesting a different
      ontogeny for these 2 categories. We also show that subset-defining sequence
      patterns in CLL differ from those underlying BCR stereotypy in other B-cell
      malignancies. Notably, 19 major subsets contained from 20 to 213 sequences each,
      collectively accounting for 943 sequences or one-eighth of the cohort. Hence,
      this compartmentalized examination of VH sequences may pave the way toward a
      molecular classification of CLL with implications for targeted therapeutic
      interventions, applicable to a significant number of patients assigned to the
      same subset.

PMID- 22415753
TI  - Hemogenic endothelium during development and beyond.
AB  - During embryonic development, multilineage HSCs/progenitor cells are derived from
      specialized endothelial cells, termed hemogenic endothelium, within the yolk sac,
      placenta, and aorta. Whether hemogenic endothelial cells contribute to blood cell
      development at other sites of definitive hematopoiesis, such as in the fetal
      liver and fetal bone marrow, is not known. Also unknown is whether such cells
      exist within the vasculature of adult bone marrow and generate hematopoietic stem
      cells after birth. These issues and their clinical relevance are discussed
      herein.

PMID- 22415754
TI  - Immune insufficiency during GVHD is due to defective antigen presentation within
      dendritic cell subsets.
AB  - Alloreactivity after transplantation is associated with profound immune
      suppression, and consequent opportunistic infection results in high morbidity and
      mortality. This immune suppression is most profound during GVHD after bone marrow
      transplantation where an inflammatory cytokine storm dominates. Contrary to
      current dogma, which avers that this is a T-cell defect, we demonstrate that the
      impairment lies within conventional dendritic cells (cDCs). Significantly,
      exogenous antigens can only be presented by the CD8(-) cDC subset after bone
      marrow transplantation, and inflammation during GVHD specifically renders the MHC
      class II presentation pathway in this population incompetent. In contrast, both
      classic and cross-presentation within MHC class I remain largely intact.
      Importantly, this defect in antigen processing can be partially reversed by TNF
      inhibition or the adoptive transfer of donor cDCs generated in the absence of
      inflammation.

PMID- 22415755
TI  - Automated microfluidic platform for studies of carbon dioxide dissolution and
      solubility in physical solvents.
AB  - We present an automated microfluidic (MF) approach for the systematic and rapid
      investigation of carbon dioxide (CO(2)) mass transfer and solubility in physical
      solvents. Uniformly sized bubbles of CO(2) with lengths exceeding the width of
      the microchannel (plugs) were isothermally generated in a co-flowing physical
      solvent within a gas-impermeable, silicon-based MF platform that is compatible
      with a wide range of solvents, temperatures and pressures. We dynamically
      determined the volume reduction of the plugs from images that were accommodated
      within a single field of view, six different downstream locations of the
      microchannel at any given flow condition. Evaluating plug sizes in real time
      allowed our automated strategy to suitably select inlet pressures and solvent
      flow rates such that otherwise dynamically self-selecting parameters (e.g., the
      plug size, the solvent segment size, and the plug velocity) could be either kept
      constant or systematically altered. Specifically, if a constant slug length was
      imposed, the volumetric dissolution rate of CO(2) could be deduced from the
      measured rate of plug shrinkage. The solubility of CO(2) in the physical solvent
      was obtained from a comparison between the terminal and the initial plug sizes.
      Solubility data were acquired every 5 min and were within 2-5% accuracy as
      compared to literature data. A parameter space consisting of the plug length,
      solvent slug length and plug velocity at the microchannel inlet was established
      for different CO(2)-solvent pairs with high and low gas solubilities. In a case
      study, we selected the gas-liquid pair CO(2)-dimethyl carbonate (DMC) and
      volumetric mass transfer coefficients 4-30 s(-1) (translating into mass transfer
      times between 0.25 s and 0.03 s), and Henry's constants, within the range of 6-12
      MPa.

PMID- 22415756
TI  - Total synthesis of exiguamines A and B inspired by catecholamine chemistry.
AB  - The evolution of a total synthesis of the exiguamines, two structurally unusual
      natural products that are highly active inhibitors of indolamine-2,3-dioxygenase
      (IDO), is described. The ultimately successful strategy involves advanced cross
      coupling methodology and features a potentially biosynthetic
      tautomerization/electrocyclization cascade reaction that forms two heterocycles
      and installs a quaternary ammonium ion in a single synthetic operation.

PMID- 22415757
TI  - Early experience for the robotic duodenum-preserving pancreatic head resection.
AB  - BACKGROUND: The duodenum-preserving pancreatic head resection (DPPHR) has been
      accepted as a valid surgical alternative to more extensive standard resections
      for the treatment of benign and low malignant tumors at the head of the pancreas.
      In this article, a new minimally invasive operation, the robot-assisted
      laparoscopic technique, is introduced for this procedure. METHODS: From March
      2010 to Dec 2010, four patients (three women and one man), with a mean age of
      42.3 years (range: 21-62 years), underwent robot-assisted laparoscopic DPPHR at
      the Hepato-Bilio-Pancreatic Surgical Department of Rui Jin Hospital in Shanghai,
      China. The preoperative symptoms include two cases of repeated upper abdominal
      pain, one case with no obvious preoperative symptoms, and one case of repeated
      hypoglycemia. The da Vinci Surgical System was used to perform the main steps of
      the operation. All patients underwent a pancreaticogastrostomy for
      pancreaticoenteric reconstruction to the distal stump. RESULTS: All four
      surgeries were successfully performed. There were no deaths. The mean operative
      time was 298.8 (270-335) min, average blood loss was 425 ml (range: 100-600 ml).
      The mean postoperative hospital stay was 26.8 days (range: 20-30 days). The one
      patient with an islet cell tumor has had normal blood glucose levels since the
      operation, and the other three patients have had no hyperglycemia. Three of the
      patients developed a pancreatic fistula that was cured by conservative treatment.
      CONCLUSIONS: The robotic surgical system is technically fully capable of
      performing the complex DPPHR procedure with an acceptable range of surgical
      complications. It breaks through the bottleneck of the traditional laparoscopic
      technology and expands the range of its applications. However, this new
      technology is still at an exploratory stage, and the long-term effect remains to
      be validated by additional clinical data.

PMID- 22415758
TI  - Identification of risk factors for esophagojejunal anastomotic leakage after
      gastric surgery.
AB  - BACKGROUND: Despite the development of the surgical technique and improvements in
      perioperative management, anastomotic leakage still occurs at esophagojejunal
      anastomoses after total or proximal gastrectomy. Anastomotic leakage is one of
      the major complications of concern, chiefly because it can lead to death. The
      objective of the present study was to identify the risk factors for
      esophagojejunal anastomotic leakage. METHODS: The study was based on
      retrospective analysis of the data of a total of 1,640 consecutive patients who
      underwent total, proximal, or completion gastrectomy, including esophagojejunal
      anastomosis, between 1999 and 2008. RESULTS: Thirty-five patients (2.1 %)
      developed anastomotic leakage. Univariate analysis revealed patient age,
      pulmonary insufficiency, lymph node dissection, combined resection of other
      organs, omental resection, operative time, blood loss, intraoperative blood
      transfusion, and postoperative creatinine level were the significant factors
      influencing anastomotic leakage. Multivariate analysis identified pulmonary
      insufficiency and the duration of the operation as the predictors of anastomotic
      leakage. CONCLUSIONS: To avoid leakage, surgeons should take care in creating the
      anastomosis in gastrectomy patients, particularly in cases of poor pulmonary
      function or when the procedure requires a longer operation.

PMID- 22415759
TI  - Prospective study of a new dynamic stabilisation system in the treatment of
      degenerative discopathy and instability of the lumbar spine.
AB  - INTRODUCTION: Posterior dynamic stabilisation (PDS) aims at relieving lumbar
      discogenic pain and preserving adjacent levels from accelerated degeneration.
      PURPOSE: To evaluate the results of a novel PDS system in 32 adult patients
      affected by chronic low back pain (CLBP) due to degenerative lumbar spine
      instability (DLSI). METHOD: A progressive follow-up for 12 months of 32 patients,
      with collection of complete clinical (ODI and VAS back + leg) and radiological
      data (resting + functional radiographs and MRI). RESULTS: Mean ODI scores
      improved from 49 to 6%, VAS back from 5 to 1 and VAS leg from 7 to 2. Twenty-two
      patients underwent fusion of a lower lumbar segment and stabilisation of an upper
      segment (hybrid fusion) whereas ten underwent dynamic stabilisation. In 16/32
      patients, decompression was added to treat radicular pain. Motion in non-fused
      instrumented levels was unrestricted on functional X-rays and MRIs did not show
      significant morphologic changes. Four patients (12.5%) had unchanged functional
      and pain scores while two (6.3%) suffered worsening low back pain necessitating
      implant removal and spinal fusion. No infection, no new neurologic deficit or
      implant failure was recorded. CONCLUSIONS: The 1 year follow-up shows that the
      tested PDS system is able to provide a significant improvement in pain and
      disability scores when applied to patients affected by DLSI. The system does not
      provide better clinical results when compared to similar trials on posterior
      fusion. Further follow-up is ongoing to investigate the potential preservation of
      adjacent levels from accelerated degeneration.

PMID- 22415760
TI  - "In situ" fusion or reduction in high-grade high dysplastic developmental
      spondylolisthesis (HDSS).
AB  - PURPOSE: To assess if the evaluation of the spino-pelvic balance can be effective
      in the surgical decision making of the high-grade high dysplastic developmental
      spondylolisthesis (HDDS). METHODS: Sixteen patients affected with high-grade HDDS
      (6 treated with "in situ" fusion, and 10 with reduction and fusion) were
      retrospectively evaluated. A clinical and radiological assessment of the
      deformity correction was carried out, with a minimum follow-up of 2 years. The
      differences between the pre- and postoperative measures were statistically
      analyzed using a two-tailed, paired t test. RESULTS: The six patients treated
      with "in situ" fusion showed no statistically significant change at the last
      follow-up relative to pelvic tilt (PT), sacral slope (SS), and grade, while the
      10 patients treated with reduction showed significant changes: PT significantly
      decreased following surgery, while SS and grade significantly increased.
      CONCLUSIONS: The analysis of the spino-pelvic sagittal balance allows to identify
      two types of HDDS: the balanced deformities, which do not need reduction, and the
      unbalanced deformities, in which correction is needed.

PMID- 22415761
TI  - The use of self-mating PEEK as an alternative bearing material for cervical disc
      arthroplasty: a comparison of different simulator inputs and tribological
      environments.
AB  - PURPOSE: The hypothesis for this study was that the simulated wear behavior of a
      hydroxyapatite coated, self-mating PEEK cervical disc arthroplasty device would
      be dependent on the simulated testing environment. METHODS: Five groups of
      devices were evaluated under suggested ASTM and ISO load and motion profiles. The
      groups utilized different testing frequencies and protein content of simulator
      fluid, in addition to assessing the potential for third body wear. The average
      wear rates were determined using linear regression analysis with a generalized
      estimating equation. Significant differences between groups were determined using
      the Wald's test. RESULTS: The simulated wear behavior was shown to be highly
      dependent on the testing environment, where protein content more than decreasing
      the cyclic loading frequency resulted in increased wear, but was not dependent on
      the suggested load and motion profiles. It was demonstrated that a self-mating
      PEEK cervical disc arthroplasty device has wear rates that are similar to
      existing material combinations for cervical disc arthroplasty. CONCLUSIONS: This
      study showed that at a time when data from retrieval analyses is deficient, it is
      important to test the wear resistance of cervical disc arthroplasty devices under
      various conditions. Long-term clinical results and ongoing implant retrievals are
      required for validation between clinical performance and simulator inputs.

PMID- 22415762
TI  - Comparative effectiveness research across two spine registries.
AB  - BACKGROUND: Comparative effectiveness research in spine surgery is still a
      rarity. In this study, pain alleviation and quality of life (QoL) improvement
      after lumbar total disc arthroplasty (TDA) and anterior lumbar interbody fusion
      (ALIF) were anonymously compared by surgeon and implant. METHODS: A total of 534
      monosegmental TDAs from the SWISSspine registry were analyzed. Mean age was 42
      years (19-65 years), 59% were females. Fifty cases with ALIF were documented in
      the international Spine Tango registry and used as concurrent comparator group
      for the pain analysis. Mean age was 46 years (21-69 years), 78% were females. The
      average follow-up time in both samples was 1 year. Comparison of back/leg pain
      alleviation and QoL improvement was performed. Unadjusted and adjusted
      probabilities for achievement of minimum clinically relevant improvements of 18
      VAS points or 0.25 EQ-5D points were calculated for each surgeon. RESULTS: Mean
      preoperative back pain decreased from 69 to 30 points at 1 year (ODelta 39pts)
      after TDA, and from 66 to 27 points after ALIF (ODelta 39pts). Mean preoperative
      QoL improved from 0.34 to 0.74 points at 1 year (ODelta 0.40pts). There were
      surgeons with better patient selection, indicated by lower adjusted probabilities
      reflecting worsening of outcomes if they had treated an average patient sample.
      ALIF had similar pain alleviation than TDA. CONCLUSIONS: Pain alleviation after
      TDA and ALIF was similar. Differences in surgeon's patient selection based on
      pain and QoL were revealed. Some surgeons seem to miss the full therapeutic
      potential of TDA by selecting patients with lower symptom severity.

PMID- 22415763
TI  - Rett networked database: an integrated clinical and genetic network of Rett
      syndrome databases.
AB  - Rett syndrome (RTT) is a neurodevelopmental disorder with one principal phenotype
      and several distinct, atypical variants (Zappella, early seizure onset and
      congenital variants). Mutations in MECP2 are found in most cases of classic RTT
      but at least two additional genes, CDKL5 and FOXG1, can underlie some (usually
      variant) cases. There is only limited correlation between genotype and phenotype.
      The Rett Networked Database (http://www.rettdatabasenetwork.org/) has been
      established to share clinical and genetic information. Through an "adaptor"
      process of data harmonization, a set of 293 clinical items and 16 genetic items
      was generated; 62 clinical and 7 genetic items constitute the core dataset; 23
      clinical items contain longitudinal information. The database contains
      information on 1838 patients from 11 countries (December 2011), with or without
      mutations in known genes. These numbers can expand indefinitely. Data are entered
      by a clinician in each center who supervises accuracy. This network was
      constructed to make available pooled international data for the study of RTT
      natural history and genotype-phenotype correlation and to indicate the proportion
      of patients with specific clinical features and mutations. We expect that the
      network will serve for the recruitment of patients into clinical trials and for
      developing quality measures to drive up standards of medical management.

PMID- 22415764
TI  - Transient aberration of neuronal development in the hippocampal dentate gyrus
      after developmental exposure to brominated flame retardants in rats.
AB  - We immunohistochemically investigated the impact and reversibility of three
      brominated flame retardants (BFRs) known to be weak thyroid hormone disruptors on
      neuronal development in the hippocampal formation and apoptosis in the dentate
      subgranular zone. Pregnant Sprague-Dawley rats were exposed to 10, 100, or 1,000
      ppm decabromodiphenyl ether (DBDE); 100, 1,000 or 10,000 ppm tetrabromobisphenol
      A (TBBPA) or 1,2,5,6,9,10-hexabromocyclododecane (HBCD) in the diet from
      gestational day 10 through to day 20 after delivery (weaning). On postnatal day
      (PND) 20, interneurons in the dentate hilus-expressing reelin increased with all
      chemicals, suggestive of aberration of neuronal migration. However, this increase
      had disappeared by PND 77. NeuN-positive mature neurons increased in the hilus on
      PND 77 with all chemicals. In the subgranular zone on PND 20, an increase in
      apoptotic bodies suggestive of impaired neurogenesis was observed after exposure
      to TBBPA or HBCD. The effects on neuronal development were detected at doses of
      >=100 ppm DBDE; >=1,000 ppm TBBPA; and at least at 10,000 ppm HBCD. On PND 20,
      the highest dose of DBDE and HBCD revealed mild fluctuations in the serum
      concentrations of thyroid-related hormones suggestive of weak developmental
      hypothyroidism, while TBBPA did not. Thus, DBDE and TBBPA may exert direct effect
      on neuronal development in the brain, but hypothyroidism may be operated for DBDE
      and HBCD at high doses. An excess of mature neurons in the hilus at later stages
      may be the signature of the developmental effects of BFRs. However, the effect
      itself was reversible.

PMID- 22415765
TI  - Cytotoxicity of hydroxyapatite nanoparticles is shape and cell dependent.
AB  - Nanosized hydroxyapatite (nHA) has been proposed as drug delivery vehicles
      because of its biocompatibility. While the possible risks of nHA inducing
      inflammation have been highlighted, the specific influence of varying nHA
      particle morphology is still unclear. In order to establish this understanding,
      nHA of four different shapes--needle (nHA-ND), plate (nHA-PL), sphere (nHA-SP)
      and rod (nHA-RD)--were synthesized. The particle effects with the concentration
      of 10-300 MUg/mL on cytotoxicity, oxygen species generation, production of
      inflammatory cytokines (TNF-alpha and IL-6), particle-cell association and
      cellular uptake were evaluated on BEAS-2B and RAW264.7 cells. Results show that
      nHA-ND and nHA-PL induced the most significant cell death in BEAS-2B cultures
      compared to nHA-SP and nHA-RD. Necrosis-apoptosis assay by FITC Annexin V and
      propidium iodide (PI) staining revealed loss of the majority of BEAS-2B by
      necrosis. No significant cell death was recorded in RAW264.7 cultures exposed to
      any of the nHA groups. Correspondingly, no significant differences were observed
      in TNF-alpha level for RAW264.7 cells upon incubation with nHA of different
      shapes. In addition, nHA-RD exhibited a higher degree of particle-cell
      association and internalization in both BEAS-2B and RAW264.7 cells, compared to
      nHA-ND. The phenomena suggested that higher particle-cell association and
      increased cellular uptake of nHA need not result in increased cytotoxicity,
      indicating the importance of particle shape on cytotoxicity. Specifically, needle
      and plate-shaped nHA induced the most significant cell-specific cytotoxicity and
      IL-6 expression but showed the least particle-cell association. Taken
      collectively, we demonstrated the shape-dependent effects of nHA on cytotoxicity,
      inflammatory cytokine expression and particle-cell association.

PMID- 22415766
TI  - Zinc as a multipurpose trace element.

PMID- 22415767
TI  - FRET microscopy in the living cell: different approaches, strengths and
      weaknesses.
AB  - New imaging methodologies in quantitative fluorescence microscopy, such as
      Forster resonance energy transfer (FRET), have been developed in the last few
      years and are beginning to be extensively applied to biological problems. FRET is
      employed for the detection and quantification of protein interactions, and of
      biochemical activities. Herein, we review the different methods to measure FRET
      in microscopy, and more importantly, their strengths and weaknesses. In our
      opinion, fluorescence lifetime imaging microscopy (FLIM) is advantageous for
      detecting inter-molecular interactions quantitatively, the intensity ratio
      approach representing a valid and straightforward option for detecting intra
      molecular FRET. Promising approaches in single molecule techniques and data
      analysis for quantitative and fast spatio-temporal protein-protein interaction
      studies open new avenues for FRET in biological research.

PMID- 22415768
TI  - Characteristics of recent biostatistical methods adopted by researchers
      publishing in general/internal medicine journals.
AB  - BACKGROUND: Novel statistical methods are constantly being developed within the
      context of biomedical research; however, the characteristics of biostatistics
      methods that have been adopted into the field of general/internal medicine (GIM)
      is unclear. This study highlights the statistical journal articles, the
      statistical journals, and the types of statistical methods that appear to be
      having the most direct impact on GIM research. METHODS: Descriptive techniques,
      including analyses of articles' keywords and controlled vocabulary terms, were
      used to characterize the articles published in statistics and probability
      journals that were subsequently referenced within GIM journal articles during a
      recent 10-year period (2000-2009). RESULTS: From the 45 statistics and
      probability journals of interest, a total of 989 unique articles were identified
      as being cited by 2183 (out of a total of about 127 469) unique GIM journal
      articles. The most frequently cited statistical topics included general/other
      statistical methods, followed by randomized trials, epidemiologic methods, meta
      analysis, generalized linear models, and computer simulation. CONCLUSION: As
      statisticians continue to develop and refine techniques, the promotion and
      adoption of these methods should also be addressed so that their efforts spent in
      developing the methods are not done in vain.

PMID- 22415769
TI  - Tetraspanins stimulate protein synthesis in myeloma cell lines.
AB  - Intensive protein synthesis is a unique and differential trait of multiple
      myeloma (MM) cells. Previously we showed that tetraspanin (CD81, CD82)
      overexpression in MM cell lines attenuated Akt/mTOR cascades, activated UPR, and
      caused autophagic death, suggesting breach of protein homeostasis. Here, we
      explored the role of protein synthesis in the tetraspanin-induced MM cell death.
      Contrary to attenuation of the major metabolic regulator, mTOR we determined
      elevated steady-state levels of protein in CD81N1/CD82N1 transfected MM lines
      (RPMI-8226, CAG). Elevated levels of immunoglobulins supported increased protein
      production in RPMI-8226. Changes in cell morphology consistent with elevated
      protein synthesis were also determined (cell, nuclei, and nucleoli sizes and
      ratios). Increased levels of phospho-rpS6 and decreased levels of phospho-AMPK
      were consistent with increased translation but independent of mTOR. Involvement
      of p38 and its role in tetraspanin induced translation and cell death were
      demonstrated. Microarray analyses of tetraspanin transfected MM cell lines
      revealed activation of protein synthesis signaling cascades and signals
      implicated in ribosome biogenesis (snoRNAs). Finally, we showed tetraspanins
      elevated protein synthesis was instrumental to MM cells' death. This work
      explores and demonstrates that excessive protein translation can be detrimental
      to MM cell lines and therefore may present a therapeutic target. Proteostasis is
      particularly important in MM because it integrates the high levels of protein
      production unique to myeloma cells with critically important microenvironmental
      cues. We suggest that increasing translation may be the path of least resistance
      in MM and thus may afford a novel platform for strategically designed therapy.

PMID- 22415770
TI  - Intravitreal triamcinolone for cancer-associated retinopathy refractory to
      systemic therapy.
AB  - PURPOSE: The purpose of this study is to report the use of intravitreal
      triamcinolone for treatment of cancer-associated retinopathy (CAR) refractory to
      systemic therapy. METHODS: This was a retrospective chart review study. RESULTS:
      A 67-year-old man presented with cancer-associated retinopathy with antibodies
      against a 46-kDa retinal protein, alpha enolase. There was disease progression
      despite therapy with mycophenolate and intravenous immunoglobulin. Serial
      intravitreal injections of triamcinolone resulted in restoration of photoreceptor
      anatomy on optical coherence tomography and visual improvement. The patient's
      vision was preserved at 20/40 OD and 20/32 OS until his death from lung cancer 31
      months after CAR diagnosis. CONCLUSIONS: Intravitreal triamcinolone may be
      beneficial for maintenance of vision in patients with CAR.

PMID- 22415772
TI  - Enantioselective alkynylbenzaldehyde cyclizations catalyzed by chiral gold(I)
      acyclic diaminocarbene complexes containing weak Au-arene interactions.

PMID- 22415774
TI  - Axial distribution of myosin binding protein-C is unaffected by mutations in
      human cardiac and skeletal muscle.
AB  - Myosin binding protein-C (MyBP-C), a major thick filament associated sarcomeric
      protein, plays an important functional and structural role in regulating
      sarcomere assembly and crossbridge formation. Missing or aberrant MyBP-C proteins
      (both cardiac and skeletal) have been shown to cause both cardiac and skeletal
      myopathies, thereby emphasising its importance for the normal functioning of the
      sarcomere. Mutations in cardiac MyBP-C are a major cause of hypertrophic
      cardiomyopathy (HCM), while mutations in skeletal MyBP-C have been implicated in
      a disease of skeletal muscle-distal arthrogryposis type 1 (DA-1). Here we report
      the first detailed electron microscopy studies on human cardiac and skeletal
      tissues carrying MyBP-C gene mutations, using samples obtained from HCM and DA-1
      patients. We have used established image averaging methods to identify and study
      the axial distribution of MyBP-C on the thick filament by averaging profile plots
      of the A-band of the sarcomere from electron micrographs of human cardiac and
      skeletal myopathy specimens. Due to the difficulty of obtaining normal human
      tissue, we compared the distribution to the A-band structure in normal frog
      skeletal, rat cardiac muscle and in cardiac muscle of MyBP-C-deficient mice. Very
      similar overall profile averages were obtained from the C-zones in cardiac HCM
      samples and skeletal DA-1 samples with MyBP-C gene mutations, suggesting that
      mutations in MyBP-C do not alter its mean axial distribution along the thick
      filament.

PMID- 22415775
TI  - Determination of single cell surface protein expression using a tagless
      microfluidic method.
AB  - We describe a method to detect the expression of a surface protein in single
      cells without prior labeling or manipulation using a microfluidic device. When
      the protein is expressed on a cell surface, it undergoes transient bond formation
      with an immobilized ligand as the cell is pumped through a microfluidic channel,
      resulting in a specific decrease in the cell's velocity. We were able to detect
      the expression of interleukin 13 receptor alpha 2 (IL13Ralpha2) differentially
      expressed on LM2 cells, a subline of MDA-MB-231 human breast cancer cells with a
      unique lung metastatic capability. The detection of cells with high expression of
      the protein was near 100% sensitive and 100% specific. We also provided proof of
      principle of multiplexing by tracking the same cell over two, differentially
      coated patches. The method is non-destructive and cells can be collected for
      reanalysis. The system can identify positive cells in a cell mixture. This method
      will have a potential impact in analyzing cancer cells when only a few are
      available, such as the case with needle aspirates and when labeling and
      manipulation result in cell loss.

PMID- 22415776
TI  - Stably integrated and expressed retroviral sequences can influence nuclear
      location and chromatin condensation of the integration locus.
AB  - The large-scale chromatin organization of retrovirus and retroviral gene vector
      integration loci has attracted little attention so far. We compared the nuclear
      organization of transcribed integration loci with the corresponding loci on the
      homologous chromosomes. Loci containing gamma-retroviral gene transfer vectors in
      mouse hematopoietic precursor cells showed small but significant repositioning of
      the integration loci towards the nuclear interior. HIV integration loci in human
      cells showed a significant repositioning towards the nuclear interior in two out
      of five cases. Notably, repositioned HIV integration loci also showed chromatin
      decondensation. Transcriptional activation of HIV by sodium butyrate treatment
      did not lead to a further enhancement of the differences between integration and
      homologous loci. The positioning relative to splicing speckles was
      indistinguishable for integration and homologous control loci. Our data show that
      stable retroviral integration can lead to alterations of the nuclear chromatin
      organization, and has the potential to modulate chromatin structure of the host
      cell. We thus present an example where a few kb of exogenous DNA are sufficient
      to significantly alter the large-scale chromatin organization of an endogenous
      locus.

PMID- 22415778
TI  - The complex of immunoglobulin A and uromodulin as a diagnostic marker for
      immunoglobulin A nephropathy.
AB  - BACKGROUND: The only tool to diagnose immunoglobulinn A nephropathy (IgAN) is
      renal biopsy which requires hospitalization; moreover, renal biopsy has a risk of
      critical bleeding. Therefore, a non-invasive method for accurate diagnosis of
      IgAN is desirable and a must-to-have tool for the clinics. For this purpose, we
      evaluated the diagnostic value of the IgA-uromodulin complex in the urine of
      patients with IgAN for its feasibility and adequacy. METHOD: We determined the
      IgA-uromodulin complex as a candidate for a diagnostic marker of IgAN by
      immunoprecipitation, liquid chromatography-mass spectrometry (LC-MS) and Western
      blot analysis. The enzyme-linked immunosorbent assay (ELISA) for the IgA
      uromodulin complex was developed and applied to urine samples obtained from
      various kidney disease patients. RESULT: One hundred and three of 126 urine
      samples (81.7%) from IgAN patients were positive for the IgA-uromodulin complex,
      while only 25 out of 94 urine samples (26.6%) in other kidney disease patients
      were positive. Sensitivity was 81.7%, specificity was 73.4%, and diagnosis
      efficiency was 78.2%. The complex was negative in eight urine samples obtained
      from patients with Alport syndrome which is almost impossible to discriminate
      from IgAN by routine urinalysis. CONCLUSION: Detection of the urinary IgA
      uromodulin complex by ELISA is a useful non-invasive method to diagnose IgAN.

PMID- 22415777
TI  - Proteomic and protein interaction network analysis of human T lymphocytes during
      cell-cycle entry.
AB  - Regulating the transition of cells such as T lymphocytes from quiescence (G(0))
      into an activated, proliferating state involves initiation of cellular programs
      resulting in entry into the cell cycle (proliferation), the growth cycle
      (blastogenesis, cell size) and effector (functional) activation. We show the
      first proteomic analysis of protein interaction networks activated during entry
      into the first cell cycle from G(0). We also provide proof of principle that
      blastogenesis and proliferation programs are separable in primary human T cells.
      We employed a proteomic profiling method to identify large-scale changes in
      chromatin/nuclear matrix-bound and unbound proteins in human T lymphocytes during
      the transition from G(0) into the first cell cycle and mapped them to form
      functionally annotated, dynamic protein interaction networks. Inhibiting the
      induction of two proteins involved in two of the most significantly upregulated
      cellular processes, ribosome biogenesis (eIF6) and hnRNA splicing (SF3B2/SF3B4),
      showed, respectively, that human T cells can enter the cell cycle without growing
      in size, or increase in size without entering the cell cycle.

PMID- 22415779
TI  - p38 Mitogen-activated protein kinase signaling, ERCC1 expression, and viability
      of lung cancer cells from never or light smoker patients.
AB  - BACKGROUND: Expression of DNA-repair proteins and activated mitogen-activated
      protein kinases (MAPKs) may differ according to smoking status. The authors
      investigated whether p38 MAPK activity contributed to the viability of cisplatin
      in lung cancer cell lines from never or light smokers and to ERCC1 mRNA
      expression. METHODS: Activated p38 MAPK was tested as a predictor for ERCC1
      levels in 117 lung adenocarcinomas. Cell viabilities of NCI-H1975, NCI-H1793, NCI
      H1650, and NCI-H1651 cell lines, derived from never or light smokers, were
      measured after treatment with the p38 MAPK inhibitor SB202190 and cisplatin. The
      role of p38alpha (MAPK14) and p38beta (MAPK11) isoforms and ERCC1 was evaluated
      using RNA interference. RESULTS: ERCC1 protein-level expression was predicted by
      activated p38 MAPK in lung adenocarcinoma tissues. The p38-specific inhibitor
      SB202190 strongly decreased cell viability (43%-63%). SB202190 plus cisplatin
      significantly decreased cell viability in every cell line, including cisplatin
      resistant NCI-H1793. Genetic inhibition, targeting both MAPK11 and MAPK14,
      reduced the viability of the different cell lines: down-regulation of p38beta
      accounted for most of this effect. Cisplatin's effect was greater after MAPK11
      down-regulation for NCI-H1651, and MAPK14 down-regulation for NCI-H1650. In
      addition, both SB202190 and MAPK11 inhibition reduced excision repair cross
      complementing 1 mRNA levels. CONCLUSIONS: Lung cancer cells from never or light
      smokers rely on p38 MAPK signaling for survival. MAPK11 is involved in that
      pathway and might contribute to ERCC1 expression. Sensitization to cisplatin can
      be achieved by pharmacological inhibition of p38 MAPK signaling.

PMID- 22415780
TI  - Extracellular polymeric substances (EPS) from aerobic granular sludges:
      extraction, fractionation, and anionic properties.
AB  - A multi-method protocol previously proposed for the extraction of extracellular
      polymeric substances (EPS) from flocculated sludges was investigated on dense
      aerobic granules. The protocol combines mechanical disruption by sonication and
      chemical extraction using the Tween detergent and the cation chelator, EDTA.
      Polysaccharides were mainly recovered during the first sonication step while
      proteins were recovered all along the extractive procedure with a high prevalence
      in the EDTA step. These data confirmed the interest of the multi-method protocol
      for harvesting a diversified pool of EPS from dense granules and for
      fractionation of the polymers according to their physicochemical properties. In
      addition, the high extractability of proteins with EDTA confers a specific
      behavior of the aerobic granules towards the multi-method extraction protocol,
      supporting the idea that proteins are associated in the granule matrix through
      ionic interactions involving divalent cations. Analysis of the extracted EPS by
      anionic exchange chromatography confirmed the presence of highly anionic proteins
      that were specifically detected in the extracts obtained from granules. One
      important question is now to investigate whether these highly anionic proteins
      are involved in the aggregation and densification process and if their presence
      is related to the cohesive properties of these particles.

PMID- 22415781
TI  - Production of alkaline protease by Bacillus altitudinis GVC11 using castor husk
      in solid-state fermentation.
AB  - Castor (Ricinus communis L.) is an important oil seed crop having its main
      cultivated area in India, China, and Brazil in dry land farming. Castor husk is
      generated as waste in castor oil production. Use of castor husk waste as
      substrate is studied for alkaline protease production by Bacillus altitudinis
      GVC11 in solid-state fermentation. Various parameters like moisture content,
      incubation period, particle size, effect of carbon and nitrogen sources are
      studied and optimized for enzyme production. Highest enzyme production of 419,293
      units per gram husk is obtained. Cost of enzyme production can be reduced by
      using castor husk as substrate.

PMID- 22415782
TI  - Subtractive genomics approach to identify putative drug targets and
      identification of drug-like molecules for beta subunit of DNA polymerase III in
      Streptococcus species.
AB  - The prolonged use of the antibiotics over the years has transformed many
      organisms resistant to multiple drugs. This has made the field of drug discovery
      of vital importance in curing various infections and diseases. The drugs act by
      binding to a specific target protein of prime importance for the cell's survival.
      Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes
      are the few gram positive organisms that have developed resistance to drugs. It
      causes pneumonia, meningitis, pharyngitis, otitis media, sinusitis, bacteremia,
      pericarditis, and arthritis infections. The present study was carried out to
      identify potential drug targets and inhibitors for beta subunit of DNA polymerase
      III in these three Streptococcus species that might facilitate the discovery of
      novel drugs in near future. Various steps were adopted to find out novel drug
      targets. And finally 3D structure of DNA polymerase III subunit beta was modeled.
      The ligand library was generated from various databases to find the most suitable
      ligands. All the ligands were docked using Molegro Virtual Docker and the lead
      molecules were investigated for ADME and toxicity.

PMID- 22415783
TI  - Examining the potential of plasma-assisted pretreated wheat straw for enzyme
      production by Trichoderma reesei.
AB  - Plasma-assisted pretreated wheat straw was investigated for cellulase and
      xylanase production by Trichoderma reesei fermentation. Fermentations were
      conducted with media containing washed and unwashed plasma-assisted pretreated
      wheat straw as carbon source which was sterilized by autoclavation. To account
      for any effects of autoclavation, a comparison was made with unsterilized media
      containing antibiotics. It was found that unsterilized washed plasma-assisted
      pretreated wheat straw (which contained antibiotics) was best suited for the
      production of xylanases (110 IU ml(-1)) and cellulases (0.5 filter paper units
      (FPU) ml(-1)). Addition of Avicel boosted enzyme titers with the highest
      cellulase titers (1.5 FPU ml(-1)) found with addition of 50 % w/w Avicel and with
      the highest xylanase production (350 IU ml(-1)) reached in the presence of 10 %
      w/w Avicel. Comparison with enzyme titers from other nonrefined feedstocks
      suggests that plasma pretreated wheat straw is a promising and suitable substrate
      for cellulase and hemicellulase production.

PMID- 22415784
TI  - Effects of different amino acids in culture media on surfactin variants produced
      by Bacillus subtilis TD7.
AB  - Surfactin produced by Bacillus subtilis has different variants, which are
      affected by the composition of substrate available. To demonstrate the effects of
      amino acids on surfactin variants, B. subtilis TD7 was cultivated under the same
      conditions but with different amino acids supplied in media, respectively, and
      the type as well as the proportion of surfactin variants produced was analyzed
      with electrospray ionization mass spectrometry and gas chromatography-mass
      spectrometry. The result shows that the addition of different amino acids
      significantly influences the proportion of surfactin variants with different
      fatty acids. When Arg, Gln, or Val was added to the culture medium of B. subtilis
      TD7, the proportion of produced surfactin variants with even beta-hydroxy fatty
      acids significantly increased, while the addition of Cys, His, Ile, Leu, Met,
      Ser, or Thr enhanced the proportion of surfactin variants with odd beta-hydroxy
      fatty acids markedly. This result may be of some reference value in enhancing the
      production of specific surfactin variants as well as in the research on the
      relationship between culture media and the corresponding products of a certain
      bacterium.

PMID- 22415785
TI  - Granulation of nitrifying bacteria in a sequencing batch reactor for biological
      stabilisation of source-separated urine.
AB  - Biological stabilisation of human urine highly depends on the abundance and
      activities of nitrifying bacteria. However, it is quite difficult to enrich
      nitrifiers as bio-aggregation by self-immobilized biomass. In this study,
      granulation of nitrifying bacteria involving inoculation strategy was developed.
      Two sequencing batch reactors, the one inoculated with nitrifying bacteria and
      the other inoculated with aerobic granules, were operated in laboratory side by
      side with a feeding of urine solution. Aerobic nitrifying granules (ANG), with
      compact morphological structure and good nitrifying activity, were achieved in
      the reactor inoculated with aerobic granules. Enrichment of nitrifying bacteria
      favors the nutrient uptake, and hence, to obtain a high ammonia oxidation
      efficiency. Nonetheless, nitrite accumulation gradually dominated in reactor,
      partly attributes to a high concentration of free nitrous acid and free ammonia
      in bulk. The matured ANG had a rather stable microbial profile, as that a number
      of activated bacteria occupied the surface of granule. It was also found that ANG
      were much more impermeable than aerobic granules and activated sludge, which was
      demonstrated as smaller porosities, and therewith an excellent settleability. The
      results herein reveal that granulation of nitrifying bacteria could enrich the
      biomass to implement stabilisation of urine in biological way.

PMID- 22415786
TI  - Effects of light intensity on the growth and lipid accumulation of microalga
      Scenedesmus sp. 11-1 under nitrogen limitation.
AB  - Scenedesmus spp. have been reported as potential microalgal species used for the
      lipid production. This study investigated the effects of light intensity (at
      three levels: 50, 250, and 400 MUmol photons m(-2) s(-1)) on the growth and lipid
      production of Scenedesmus sp. 11-1 under N-limited condition. Carotenoid to
      chlorophyll ratio was higher when algae 11-1 grew under 250 and 400 MUmol photons
      m(-2) s(-1) than that under 50 MUmol photons m(-2) s(-1), while protein contents
      was lower. Highest biomass yield (3.88 g L(-1)), lipid content (41.1 %), and
      neutral lipid content (32.9 %) were achieved when algae 11-1 grew at 400 MUmol
      photons m(-2) s(-1). Lipid production was slight lower at 250 MUmol photons m(-2)
      s(-1) level compared to 400 MUmol photons m(-2) s(-1). The major fatty acids in
      the neutral lipid of 11-1 were oleic acid (43-52 %), palmitic acid (24-27 %), and
      linoleic acid (7-11 %). In addition, polyunsaturated fatty acids had a positive
      correlation with total lipid production, and monounsaturated fatty acids had a
      negative one.

PMID- 22415787
TI  - Binding and encapsulation of doxorubicin on smart pectin hydrogels for oral
      delivery.
AB  - Pectins (Pec) of 33 to 74 % esterification degree were tested with doxorubicin
      (Dox), a very high toxic drug widely used in cancer therapies. Pec with 35 and 55
      % DE were selected because of the Dox binding higher than Pec microspheres of 35
      and 55 % obtained by ionotropic gelation with Ca+2 have 88 and 66 % Dox loading
      capacity. Kinetic Dox release showed more than 80.0 and about 30.0 % free drug
      from 35 % and 55 % Pec formulations at pH 7.4, and 37  degrees C after 1-h
      incubation, respectively. Besides, Dox release decrease to 12 % in 55 % Pec
      microsphere formulation after 1-year storage at 4  degrees C. FTIR analysis of
      Pec-Dox complex showed hipsochromic shifts for the sigma(C=O), delta(N-H) and
      sigma(C-C) vibrational modes compared to Dox spectrum suggesting strong
      interaction between the drug cargo and the matrix. Rheological studies of Pec and
      Pec-Dox samples flow behavior exhibited a shear-thinning nature. Fifty-five
      percent of Pec showed higher viscosity than the viscosity for 35 % Pec in all
      range of temperatures analyzed, and decreased when the temperature is raised.
      Besides, Pec-Dox complexes have higher viscosity values than those of the
      corresponding Pec samples, and viscosity curves as function of shear rate for 35
      % Pec-Dox are above the curves of 55 % Pec-Dox. In both cases, the results are
      confirming significant interaction between the cargo and the matrix, which also
      was established in viscoelastic dynamic analysis.

PMID- 22415788
TI  - Co-culture of microalgae, cyanobacteria, and macromycetes for exopolysaccharides
      production: process preliminary optimization and partial characterization.
AB  - In this study, the biomass and exopolysaccharides (EPS) production in co-cultures
      of microalgae/cyanobacteria and macromycetes was evaluated as a technology for
      producing new polysaccharides for medical and/or industrial application. Based on
      biomass and EPS productivity of monocultures, two algae and two fungi were
      selected and cultured in different co-culture arrangements. The hydrosoluble EPS
      fractions from mono- and co-cultures were characterized by 13C NMR spectroscopy
      and gas chromatography coupled to mass spectrometry and compared. It was found
      that co-cultures resulted in the production of an EPS different from those
      produced by monocultures, showing fungal predominance with
      microalgal/cyanobacterial traces. Co-cultures conditions were screened
      (temperature, agitation speed, fungal and microalgae inoculation rate, initial
      pH, illumination rate, and glucose concentration) in order to achieve maximum
      biomass and EPS production, resulting in an increase of 33 and 61% in
      exopolysaccharides and biomass productions, respectively (patent pending).

PMID- 22415789
TI  - Production, purification, and characterization of a beta-glucosidase of
      Penicillium funiculosum NCL1.
AB  - Penicillium funiculosum NCL1, a filamentous fungus, produced significantly higher
      levels of beta-glucosidase. The effect of initial pH, incubation temperature, and
      different carbon sources on extracellular beta-glucosidase production was studied
      in submerged fermentation. At 30  degrees C with initial pH 5.0, enzyme
      production was increased by 48-fold upon induction with paper mill waste, as
      compared to commercial cellulose powder. In zymogram analysis, four isoforms of
      beta-glucosidases were observed with wheat bran whereas a minimum of one isoform
      was observed with other carbon sources. A major beta-glucosidase (Bgl3A) with the
      apparent molecular weight of ~120 kDa, induced by paper mill waste, was purified
      19-fold to homogeneity, with a specific activity of 1,796 U/mg. Bgl3A was a
      monomeric glycoprotein with 29% of neutral carbohydrate content. It showed
      optimum activity at pH 4.0 and 5.0, optimum temperature at 60  degrees C, and
      exhibited a half-life of 1 h at 60  degrees C. K(m) of Bgl3A was found to be
      0.057 mM with p-nitrophenyl beta-D-glucoside and V(max) was 1,920 U/mg. The
      purified enzyme exhibited glucose tolerance with a K(i) of 1.5 mM. Bgl3A readily
      hydrolyzed glucosides with beta-linkage. Bgl3A activity was enhanced (156%) by
      Zn2+ and was not affected by other metal cations and reagents. The
      supplementation of Bgl3A (5 U/mg) with Trichoderma reesei cellulase complex (5
      FPU/mg) resulted in about 70% of enhanced glucose production, which emphasizes
      the industrial importance of Bgl3A.

PMID- 22415790
TI  - Development of DNA-designed avian IgY antibodies for detection of Mycobacterium
      avium subsp. paratuberculosis heat shock protein 70 (Hsp70) and anti-Hsp70
      antibodies in the serum of normal cattle.
AB  - Mycobacterium avium subsp. paratuberculosis heat shock protein 70 (MAPHsp70) is
      an immunodominant antigen, which can be used as a subunit vaccine against bovine
      paratuberculosis. In the present study, we evaluated the immunogenic activities
      of MAPHsp70 expressed by DNA vaccine in chicken and the use of prepared specific
      avian IgY antibodies for western blotting and ELISA methods. The gene encoding
      MAP Hsp70 was subcloned into the eukaryotic expression vector, pcDNA3.1, and the
      recombinant plasmid (pcDNA3.1-MAP Hsp70) transfected into COS-7 cells. Chickens
      were also immunized with pcDNA3.1-MAP Hsp70, and egg yolk antibodies extracted
      from eggs were collected after immunization. DNA-designed IgY antibody was used
      in Western blotting analysis to detect the expression of MAPHsp70, and in a
      sandwich ELISA to assess the prevalence of anti-MAPHsp70 antibodies in cattle
      serum. Western blotting results indicate the expression of rMAP hsp70 in COS-7
      cells and sandwich ELISA could detect anti-MAPHsp70 antibodies in 7.5% of cows.
      Chicken immunization with pcDNA3.1-MAPHsp70 could demonstrate the effective
      production of anti-MAPHsp70 IgY antibodies. Monospecific anti-MAPHsp70 antibody
      generated in chickens is useful for detection of MAPHsp70 peptide in cell culture
      and MAP lysate.

PMID- 22415791
TI  - Microsomal epoxide hydrolase polymorphisms, cigarette smoking, and risk of
      colorectal cancer: the Fukuoka Colorectal Cancer Study.
AB  - Microsomal epoxide hydrolase (EPHX1) plays an important role in the activation
      and detoxification of polycyclic aromatic hydrocarbons, carcinogens found in
      cigarette smoke. Polymorphisms in exon 3 (Y113H) and exon 4 (H139R) of the EPHX1
      have been associated with enzyme activity. We investigated the risk of colorectal
      cancer in relation to the EPHX1 Y113H and H139R polymorphisms and assessed effect
      modifications of cigarette smoking and the other covariates. The interaction
      between the EPHX1 polymorphisms and selected genetic polymorphisms was also
      examined. We used data from Fukuoka Colorectal Cancer Study, a community-based
      case-control study, including 685 cases and 778 controls. In-person interviews
      were conducted to assess lifestyle factors. The EPHX1 Y113H and H139R
      polymorphisms were determined by the TaqMan assay and the polymerase chain
      reaction-restriction fragment length polymorphism, respectively. Neither of the
      two polymorphisms nor the imputed EPHX1 phenotype was associated with colorectal
      cancer risk. Cigarette smoking and alcohol intake showed no effect modification
      on the association with the EPHX1 polymorphisms or the imputed EPHX1 phenotype.
      Increased risks of colorectal cancer associated with the 113Y allele and imputed
      EPHX1 phenotype were observed among individuals with high body mass index (BMI;
      >=25.0 kg/m(2)), but not among those with low BMI (<25.0 kg/m(2)). The risk
      decreased with an increasing number of the 139R allele in the null genotypes of
      GSTM1/GSTT1. It is unlikely that the EPHX1 polymorphisms play an important role
      in colorectal carcinogenesis. The observed interactions of the EPHX1
      polymorphisms with BMI and the GSTM1/GSTT1 genotypes warrant further
      investigation.

PMID- 22415792
TI  - Defining female voiding dysfunction: ICI-RS 2011.
AB  - Whilst symptoms of bladder outlet obstruction (BOO) and post micturition symptoms
      are more commonly reported in men a significant number of women may also complain
      of voiding dysfunction. However, despite the recent advances in the
      standardisation of terminology of lower urinary tract dysfunction there remains a
      lack of consensus regarding a precise diagnosis and definition of voiding
      abnormalities in women. In addition voiding symptoms may co-exist with storage
      symptoms as well as those associated with urinary incontinence. Consequently many
      patients present with a spectrum of different urinary symptoms, related to both
      storage and voiding, which may be multifactorial in origin or be related to one
      another. The purpose of this paper is to review the current literature in order
      to accurately define and classify female voiding dysfunction including causes and
      aetiology. In addition to reviewing the investigation and management of those
      women with voiding dysfunction recommendations are proposed for management in
      clinical practice as well as suggestions for future research.

PMID- 22415793
TI  - Formal synthesis of (-)-englerin A and cytotoxicity studies of truncated
      englerins.
AB  - An efficient formal synthesis of (-)-englerin A (1) is reported. The target
      molecule is a recently isolated guaiane sesquiterpene that possesses highly
      potent and selective activity against renal cancer cell-lines. Our
      enantioselective strategy involved the construction of the BC ring system of
      compound 1 through a Rh(II)-catalyzed [4+3] cycloaddition reaction followed by
      subsequent attachment of the A ring through an intramolecular aldol condensation
      reaction. As such, this strategy allows the synthesis of truncated englerins.
      Evaluation of these analogues with the A498 renal cancer cell-line suggested that
      the A ring of englerin is crucial to its antiproliferative activity. Moreover,
      evaluation of these analogues led to the identification of potent growth
      inhibitors of CEM cells with GI(50) values in the range 1-3 MUM.

PMID- 22415794
TI  - Complex formation between heme oxygenase and phytochrome during biosynthesis in
      Pseudomonas syringae pv. tomato.
AB  - The plant pathogen Pseudomonas syringae pv. tomato carries two genes encoding
      bacterial phytochromes. Sequence motifs identify both proteins (PstBphP1 and
      PstBphP2, respectively) as biliverdin IXalpha (BV)-binding phytochromes. PstbphP1
      is arranged in an operon with a heme oxygenase (PstBphO)-encoding gene (PstbphO),
      whereas PstbphP2 is flanked downstream by a gene encoding a CheY-type response
      regulator. Expression of the heme oxygenase PstBphO yielded a green protein
      (lambda(max) = 650 nm), indicative for bound BV. Heterologous expression of
      PstbphP1 and PstbphP2 and in vitro assembly with BV IXalpha yielded the
      apoproteins for both phytochromes, but only in the case of PstBphP1 a light
      inducible chromoprotein. Attempts to express the endogenous heme oxygenase BphO
      and either of the two phytochromes from two plasmids yielded only holo-PstBphP1.
      Relatively small amounts of soluble holo-PstBphP2 were just obtained upon co
      expression with BphO from P. aeruginosa. Expression of the operon containing
      PstbphO:PstbphP1 led to an improved yield and better photoreactivity for
      PstBphP1, whereas an identical construct, exchanging PstbphP1 for PstbphP2
      (PstbphO:PstbphP2), again yielded only minute amounts of chromophore-loaded BphP2
      holoprotein. The improved yield for PstBphP1 from the PstbphO:PstbphP1 operon
      expression is apparently caused by complex formation between both proteins during
      biosynthesis as affinity chromatography of either protein using two different
      tags always co-purified the reaction partner. These results support the
      importance of protein-protein interactions during tetrapyrrole metabolism and
      phytochrome assembly.

PMID- 22415795
TI  - First report of the safety, tolerability, and pharmacokinetics of the Src kinase
      inhibitor saracatinib (AZD0530) in Japanese patients with advanced solid tumours.
AB  - BACKGROUND: Saracatinib (AZD0530) is a selective, oral Src inhibitor that has
      demonstrated antitumour activity in preclinical studies. METHODS: This open
      label, dose-escalation, phase I study evaluated the safety and tolerability of
      saracatinib in Japanese patients with advanced solid tumours (clinicaltrials.gov
      NCT00704366). Patients received continuous once-daily oral dosing with
      saracatinib starting 7 days after a single dose in ascending dose cohorts until
      dose-limiting toxicity (DLT) or disease progression. Pharmacokinetics and
      efficacy were also evaluated. RESULTS: A total of 12 patients received
      saracatinib at doses of 50 (n = 3), 125 (n = 6), and 175 mg (n = 3). Median
      durations of exposure were 65, 44, and 16 days in the 50, 125, and 175 mg
      cohorts, respectively. The most common adverse events were diarrhoea (67 %),
      nausea (67 %), decreased appetite (58 %), lymphopenia (50 %) and pyrexia (50 %).
      The most common grade >=3 adverse events were leukopenia, lymphopenia,
      neutropenia, and haemoglobin decreased (all 17 %). DLTs occurred in two patients,
      both in the 175 mg cohort: grade 3 aspartate aminotransferase increased with
      grade 3 gamma-glutamyltransferase increased (n = 1); and grade 3 hypoxia (n = 1).
      Following a single dose, saracatinib median t(max) across the doses was 2-4 h,
      and thereafter plasma concentrations declined in a biphasic manner, with mean
      terminal half-life of approximately 45 h. Geometric mean saracatinib exposures
      were 0.8-2.1 times greater than those reported in Caucasian patients. The best
      response was stable disease (50 mg, n = 2; 125 mg, n = 1). CONCLUSIONS:
      Saracatinib was tolerated in Japanese patients with advanced solid tumours at
      doses up to 125 mg.

PMID- 22415796
TI  - Evaluation of deoxyhypusine synthase inhibitors targeting BCR-ABL positive
      leukemias.
AB  - Effective inhibition of BCR-ABL tyrosine kinase activity with Imatinib represents
      a breakthrough in the treatment of patients with chronic myeloid leukemia (CML).
      However, more than 30 % of patients with CML in chronic phase do not respond
      adequately to Imatinib and the drug seems not to affect the quiescent pool of BCR
      ABL positive leukemic stem and progenitor cells. Therefore, despite encouraging
      clinical results, Imatinib can still not be considered a curative treatment
      option in CML. We recently reported downregulation of eukaryotic initiation
      factor 5A (eIF5A) in Imatinib treated K562 cells. Furthermore, the inhibition of
      eIF5A by siRNA in combination with Imatinib has been shown to exert synergistic
      cytotoxic effects on BCR-ABL positive cell lines. Based on the structure of known
      deoxyhypusine synthase (DHS) inhibitors such as CNI-1493, a drug design approach
      was applied to develop potential compounds targeting DHS. Here we report the
      biological evaluation of selected novel (DHSI-15) as compared to established (CNI
      1493, deoxyspergualin) DHS inhibitors. We show that upon the compounds tested,
      DHSI-15 and deoxyspergualin exert strongest antiproliferative effects on BCR-ABL
      cells including Imatinib resistant mutants. However, this effect did not seem to
      be restricted to BCR-ABL positive cell lines or primary cells. Both compounds are
      able to induce apoptosis/necrosis during long term incubation of BCR-ABL positive
      BA/F3 derivates. Pharmacological synergism can be observed for deoxyspergualin
      and Imatinib, but not for DHSI-15 and Imatinib. Finally we show that
      deoxyspergualin is able to inhibit proliferation of CD34+ progenitor cells from
      CML patients. We conclude that inhibition of deoxyhypusine synthase (DHS) can be
      supportive for the anti-proliferative treatment of leukemia and merits further
      investigation including other cancers.

PMID- 22415797
TI  - Clinical development of insulin-like growth factor receptor--1 (IGF-1R)
      inhibitors: at the crossroad?
AB  - Insulin like growth factor receptor (IGF-1R) targeting became one of the most
      investigated areas in anticancer drug development during the last decade.
      Strategies aiming to block IGF-1R activity include monoclonal antibodies,
      tyrosine kinase inhibitors and anti-ligands antibodies. Initial enthusiasm
      quickly encountered challenges. Unfortunately the validation of the efficacy of
      IGF-1R targeted agents in large clinical trials failed, however anecdotal single
      agent activity was seen in early studies. Consequently, questions regarding the
      selection of right target population and the appropriate trial design are
      arising. Despite the plethora of clinical trials conducted no predictive
      biomarker has been validated so far and resistance mechanisms to IGF-1R
      inhibitors remain unclear. The other issue to be addressed is how to best combine
      IGF-1R inhibitors with other therapeutic approaches. This review highlights the
      most relevant clinical data emphasizing the main tumor types where IGF-1R
      inhibition showed potential interest. We also tried to extract based on clinical
      and translational data some candidate biomarkers that could help better to select
      patient population who potentially could benefit most from this therapeutic
      approach.

PMID- 22415798
TI  - A phase I study of sorafenib and vorinostat in patients with advanced solid
      tumors with expanded cohorts in renal cell carcinoma and non-small cell lung
      cancer.
AB  - BACKGROUND: This phase I study evaluated the safety, tolerability and preliminary
      efficacy of sorafenib combined with vorinostat in patients with solid tumors.
      PATIENTS AND METHODS: Patients were treated with sorafenib 400 mg po bid daily
      and vorinostat 200-400 mg po days 1-14 of a 21 day cycle to establish the
      recommended phase II dose (RP2D). The tolerability and efficacy of the RP2D was
      further tested in two cohorts of 6-12 patients each with advanced RCC and NSCLC.
      RESULTS: 17 patients were treated in the dose escalation phase that established
      the RP2D at sorafenib 400 mg po bid daily, vorinostat 300 mg po days 1-14. Dose
      limiting toxicities (DLT) included intolerable grade 2 hand-foot syndrome and
      multiple grade 1 toxicities causing dose interruption for more than 14 days.
      Despite good tolerance in the all-comers population, the RP2D was poorly
      tolerated in the RCC and NSCLC cohorts with the majority being unable to finish 2
      full cycles of therapy. Although there were no confirmed responses, 1 patient
      each with NSCLC adenocarcinoma and renal sarcoma had unconfirmed partial
      responses and 5 of 8 patients with RCC having durable minor responses (11-26 %),
      including 2 who were on treatment for nearly a year. CONCLUSIONS: Although
      tolerable in other tumor types, sorafenib 400 mg po bid with vorinostat 300 mg po
      daily days 1-14 of a 21-day cycle is not tolerable without dose reductions/delays
      in RCC and NSCLC patients. These patients may require lower doses than the RP2D
      explored within this study. No confirmed responses were seen but minor responses
      particularly in RCC were observed.

PMID- 22415799
TI  - Scandium(III)-zeolites as new heterogeneous catalysts for imino-Diels-Alder
      reactions.
AB  - This study demonstrates the first zeolite-catalyzed synthesis of piperidine
      derivatives, including peptidomimetics and indoloquinolizidine alkaloids. The
      approach developed utilizes a highly effective one-pot reaction cascade, through
      imine formation and imino-Diels-Alder reactions, promoted by scandium-loaded
      zeolites as a heterogeneous catalyst. The methodology described benefits from
      very low catalyst loadings (<=5 mol % of Sc(III) ), commercially and readily
      available starting materials, and mild reaction conditions. Furthermore, the
      Sc(III) -zeolite catalyst can be readily reused more than 10 times without any
      loss in efficiency.

PMID- 22415800
TI  - Mutual influence between halogen bonds and cation-pi interactions: a theoretical
      study.
AB  - The interplay between halogen bonds and cation-pi interactions is investigated by
      ab initio calculations at the MP2 level of theory. Different energetic effects
      are observed in the studied complexes in which halogen bonds and cation-pi
      interactions coexist, which can be ascribed to the direction of charge transfer
      for the two interactions. These effects are analyzed in detail in terms of the
      structural, energetic, and charge-transfer properties of the complexes. In
      addition, the quantum theory of atoms in molecules is employed to characterize
      the interactions and to examine their enhancement and attenuation in terms of the
      variations in electron density at the bond and cage critical points. Finally,
      experimental evidence for a combination of the two interactions is obtained from
      the Cambridge Structural Database.

PMID- 22415801
TI  - Calibration of the motor-assisted robotic stereotaxy system: MARS.
AB  - BACKGROUND: The motor-assisted robotic stereotaxy system presents a compact and
      light-weight robotic system for stereotactic neurosurgery. Our system is designed
      to position probes in the human brain for various applications, for example, deep
      brain stimulation. It features five fully automated axes. High positioning
      accuracy is of utmost importance in robotic neurosurgery. METHODS: First, the key
      parameters of the robot's kinematics are determined using an optical tracking
      system. Next, the positioning errors at the center of the arc--which is
      equivalent to the target position in stereotactic interventions--are investigated
      using a set of perpendicular cameras. A modeless robot calibration method is
      introduced and evaluated. To conclude, the application accuracy of the robot is
      studied in a phantom trial. RESULTS: We identified the bending of the arc under
      load as the robot's main error source. A calibration algorithm was implemented to
      compensate for the deflection of the robot's arc. The mean error after the
      calibration was 0.26 mm, the 68.27th percentile was 0.32 mm, and the 95.45th was
      0.50 mm. CONCLUSION: The kinematic properties of the robot were measured, and
      based on the results an appropriate calibration method was derived. With mean
      errors smaller than currently used mechanical systems, our results show that the
      robot's accuracy is appropriate for stereotactic interventions.

PMID- 22415802
TI  - Angiogenic functionalisation of titanium surfaces using nano-anchored VEGF - an
      in vitro study.
AB  - The aim of the present study was to test the hypothesis that sandblasted and acid
      etched titanium surfaces can be functionalised with vascular endothelial growth
      factor (VEGF) using oligonucleotides for anchorage and slow release. rhVEGF165
      molecules were conjugated to strands of 30-mer non-coding DNA oligonucleotides
      (ODN) and hybridised to complementary ODN anchor strands which had been
      immobilised to the surface of sandblasted/acid etched (SAE) Ti specimens.
      Specimens with non-conjugated VEGF adsorbed to ODN anchor strands and to blank
      SAE surfaces served as controls. Specific binding of conjugated VEGF exhibited
      the highest percentage of immobilised VEGF (71.0 %), whereas non-conjugated VEGF
      only achieved 53.2 and 30.7 %, respectively. Cumulative release reached 54.0 % of
      the immobilised growth factor in the group of specifically bound VEGF after 4
      weeks, whereas non-conjugated VEGF adsorbed to ODN strands released 78.9% and
      VEGF adsorbed to SAE Ti surfaces released 97.4 %. Proliferation of human
      umbilical vein endothelial cells (HUVECs) was significantly increased on the
      surfaces with specifically bound VEGF compared to the control surfaces and SAE Ti
      surfaces without VEGF. Moreover, the released conjugated VEGF exhibited
      biological activity by induction of von Willebrand Factor (vWF) in mesenchymal
      stem cells. It is concluded that the angiogenic functionalisation of SAE titanium
      surfaces can be achieved by conjugation of VEGF to ODN strands and hybridisation
      to complementary ODN strands that are anchored to the titanium surface. The
      angiogenic effect is exerted both through the immobilised and the released
      portion of the growth factor.

PMID- 22415803
TI  - Multivalent structure of galectin-1-nanogold complex serves as potential
      therapeutics for rheumatoid arthritis by enhancing receptor clustering.
AB  - Cellular behaviour is controlled by numerous processes, including intracellular
      signalling pathways that are triggered by the binding of ligands with cell
      surface receptors. Multivalent ligands have multiple copies of a recognition
      element that binds to receptors and influences downstream signals. Nanoparticle
      ligand complexes may form multivalent structures to crosslink receptors with high
      avidity and specificity. After conjugation onto gold nanoparticles, galectin-1
      (Au-Gal1) bound with higher affinity to Jurkat cells to promote CD45 clustering
      and inhibition of its phosphatase activity, resulting in enhancement of apoptosis
      via caspase-dependent pathways. Au-Gal1 injected intra-articularly into rats with
      collagen-induced arthritis (CIA) promoted apoptosis of CD4+ T cells and reduced
      pro-inflammatory cytokine levels in the ankle joints as well as ameliorated
      clinical symptoms of arthritis. These observed therapeutic effects indicate that
      the multivalent structure of nanoparticle-ligands can regulate the distribution
      of cell surface receptors and subsequent intracellular signalling, and this may
      provide new insights into nanoparticle applications.

PMID- 22415804
TI  - Dynamic cell adhesion and migration on nanoscale grooved substrates.
AB  - Organised nanotopography mimicking the natural extracellular matrix can be used
      to control morphology, cell motility, and differentiation. However, it is still
      unknown how specific cell types react with specific patterns. Both initial
      adhesion and preferential cell migration may be important to initiate and
      increase cell locomotion and coverage with cells, and thus achieve an enhanced
      wound healing response around an implantable material. Therefore, the aim of this
      study was to evaluate how MC3T3-E1 osteoblast initial adhesion and directional
      migration are influenced by nanogrooves with pitches ranging from 150 nm up to
      1000 nm. In this study, we used a multi-patterned substrate with five different
      groove patterns and a smooth area with either a concentric or radial orientation.
      Initial cell adhesion measurements after 10 s were performed using atomic force
      spectroscopy-assisted single-cell force spectroscopy, and demonstrated that
      nascent cell adhesion was highly induced by a 600 nm pitch and reduced by a 150
      nm pitch. Addition of RGD peptide significantly reduced adhesion, indicating that
      integrins and cell adhesive proteins (e.g. fibronectin or vitronectin) are key
      factors in specific cell adhesion on nanogrooved substrates. Also, cell migration
      was highly dependent on the groove pitch; the highest directional migration
      parallel to the grooves was observed on a 600 nm pitch, whereas a 150 nm pitch
      restrained directional cell migration. From this study, we conclude that grooves
      with a pitch of 600 nm may be favourable to enhance fast wound closure, thereby
      promoting tissue regeneration.

PMID- 22415805
TI  - Using PhenX measures to identify opportunities for cross-study analysis.
AB  - The PhenX Toolkit provides researchers with recommended, well-established, low
      burden measures suitable for human subject research. The database of Genotypes
      and Phenotypes (dbGaP) is the data repository for a variety of studies funded by
      the National Institutes of Health, including genome-wide association studies. The
      dbGaP requires that investigators provide a data dictionary of study variables as
      part of the data submission process. Thus, dbGaP is a unique resource that can
      help investigators identify studies that share the same or similar variables. As
      a proof of concept, variables from 16 studies deposited in dbGaP were mapped to
      PhenX measures. Soon, investigators will be able to search dbGaP using PhenX
      variable identifiers and find comparable and related variables in these 16
      studies. To enhance effective data exchange, PhenX measures, protocols, and
      variables were modeled in Logical Observation Identifiers Names and Codes
      (LOINC(r) ). PhenX domains and measures are also represented in the Cancer Data
      Standards Registry and Repository (caDSR). Associating PhenX measures with
      existing standards (LOINC(r) and caDSR) and mapping to dbGaP study variables
      extends the utility of these measures by revealing new opportunities for cross
      study analysis.

PMID- 22415806
TI  - Highly efficient asymmetric Michael addition of diaryl phosphine oxides to
      alpha,beta-unsaturated N-acylated oxazolidin-2-ones.

PMID- 22415807
TI  - Functional polymorphisms in the insulin-like binding protein-3 gene may modulate
      susceptibility to differentiated thyroid carcinoma in Caucasian Americans.
AB  - The insulin-like growth factor (IGF) pathway is believed to play a pivotal role
      in thyroid carcinogenesis. Polymorphisms of IGF-1 and IGF binding protein-3
      (IGFBP-3) have been associated with modulation of risk for the emergence of
      assorted common malignancies, but studies of the influence of such polymorphisms
      on risk of differentiated thyroid carcinoma (DTC) are lacking. In a case-control
      study of 173 DTC patients, 101 patients with benign thyroid disease, and 401
      controls, an unconditional logistical regression model adjusted for age and sex
      was applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for
      the associations between polymorphisms of IGF-1 and IGFBP-3 and DTC risk. IGFBP-3
      rs2132572 GA/AA genotypes were associated with a decreased risk of DTC (adjusted
      OR = 0.6, 95% CI: 0.4-0.9), particularly multifocal DTC (adjusted OR = 0.3, 95%
      CI: 0.1-0.7). The association with DTC was more evident in subjects with a first
      degree family history of cancer (adjusted OR = 0.4, 95% CI: 0.2-0.7,
      P(interaction)  = 0.013) and non-drinkers (adjusted OR = 0.4, 95% CI: 0.2-0.7,
      P(interaction)  = 0.028). A four single nucleotide polymorphism haplotype of
      IGFBP-3 was associated with a decreased risk of DTC (adjusted OR = 0.7, 95% CI:
      0.5-1.0, P = 0.030). Our study suggests that polymorphic IGFBP-3 may be involved
      in susceptibility to DTC.

PMID- 22415808
TI  - How should bladder sensation be measured? ICI-RS 2011.
AB  - AIMS: Disturbed bladder sensations, or in broader terms, sensory dysfunctions are
      increasingly recognized as key elements in the origin and manifestation of
      symptom syndromes of urinary dysfunction. Adequate assessment of bladder
      sensation is crucial to improve our understanding of the pathophysiology and
      treatment of urinary dysfunction. This manuscript summarizes the discussions of a
      think tank on "How to measure bladder sensation" held at the ICI-RS meeting in
      2011. METHODS: Based upon literature reviews on bladder sensation presented at
      the think tank in the ICI-RS meeting, discussions evolved which were summarized
      in the ICI-RS report. Different physicians/researchers further elaborated on this
      report, which is presented in this manuscript. RESULTS: Bladder sensations are
      not merely the result of bladder distension. Other factors inside the bladder or
      bladder wall: central processing and/or cognitive manipulation may play an
      important role. Current methods to measure sensations such as urodynamics,
      voiding diaries, forced diuresis, electrical stimulation and brain imaging are
      likely sub-optimal as they only consider part of these factors in isolation.
      CONCLUSIONS: Different methods to measure bladder sensations have been described
      and are used in clinical practice. Current methods only address part of the
      parameters responsible for the generation and perception of urinary sensations.
      Further focused research is required, and several recommendations are provided.

PMID- 22415809
TI  - Characteristic imaging features of body packers: a pictorial essay.
AB  - The drug-trafficking business has risen tremendously because of the current
      increased demand for illegal narcotics. The smugglers conceal the drugs in their
      bodies (body packers) in order to bypass the tight security at international
      borders. A suspected body packer will normally be sent to the hospital for
      imaging investigations to confirm the presence of drugs in the body.
      Radiologists, therefore, need to be familiar with and able to identify drug
      packets within the human body because they shoulder the legal responsibilities.
      This pictorial essay describes the characteristic imaging features of drug
      packets within the gastrointestinal tract.

PMID- 22415810
TI  - The relationship between receiving care within a medical home and HPV vaccine
      receipt for adolescent girls: results of the 2007 National Survey of Children's
      Health.
AB  - To estimate initiation of HPV vaccination among adolescent girls and examine the
      relationship between receiving care consistent with the medical home model in a
      population-based sample. We used the National Survey of Children's Health 2007, a
      nationally representative sample of children in the United States, to study
      adolescent girls 12-17 years of age. We present the results of descriptive and
      multivariable logistic regression analyses for the relationship between receiving
      care within a medical home, as defined by the American Academy of Pediatrics, and
      HPV vaccination initiation. Overall, 18.1% of adolescent girls had received at
      least one HPV vaccine injection and 54.6% received care within a medical home.
      The relationship between having a medical home and HPV vaccine initiation was
      heterogeneous across levels of household income and parent education. After
      adjusting for region of U.S., insurance status, and race/ethnicity, we found
      increased odds of HPV vaccine receipt for girls with versus without a medical
      home among those in low income households (<300% of the federal poverty level)
      whose parents have less than a high school education (OR 3.98, 95% CI 1.52
      10.44). Results were not significant for other strata of household income and
      parent education. These findings suggest the important role of receiving care in
      a medical home model in HPV vaccine adoption for adolescents in households with
      low incomes and low parent education. Continued promotion of the medical home
      model at the federal and state levels, especially within vulnerable populations,
      may help to reduce disparities in access to preventive vaccines.

PMID- 22415811
TI  - Pregnant and moving: understanding residential mobility during pregnancy and in
      the first year of life using a prospective birth cohort.
AB  - To examine residential mobility (i.e., moving) during pregnancy and in the first
      year of an infant's life using a large, prospective birth cohort in Rhode Island.
      Participants were recruited from Women and Infants Hospital of Rhode Island
      between January 5, 2009 and March 19, 2009. Residential histories were collected
      from mothers in-person immediately post-partum and by phone at 7 months and at 13
      months post-partum. Of 1,040 mothers interviewed at birth, 71% (n = 740)
      completed the 13 month follow-up interview. Forty-one percent of mothers (n =
      300) moved at least once between conception and 1 year post-partum, with the
      number of moves ranging from 0 to 8. Among movers, 69.0% moved once, 21.0% moved
      twice, and 10.0% moved three or more times. Mothers who moved tended to be
      younger, have fewer children, were not White, and had lower household incomes
      than those who did not move. Mothers who moved during pregnancy had 2.05 (95% CI:
      1.40-2.98) times the odds of moving post-partum than mothers who had not moved in
      the antenatal period. There were statistical differences across socio-demographic
      groups with regard to when, where, and why mothers moved. Forty percent of movers
      during pregnancy (n = 61) moved for at least one negative reason, while 32.2% of
      movers during infancy (n = 64) relocated under negative circumstances. A
      substantial proportion of mothers moved pre- and post-partum, frequently under
      negative circumstances. Study findings have important implications for obstetric
      and pediatric providers who seek to understand, retain, and improve the health of
      their patient populations.

PMID- 22415812
TI  - The web of risk factors for excessive gestational weight gain in low income
      women.
AB  - The objective of this study is to gain an in-depth understanding of issues
      related to gestational weight gain (GWG) including general health, diet, and
      physical activity among high and low income women and to elucidate socio
      ecological and psychosocial risk factors that increase risk for excessive GWG. We
      conducted 9 focus groups with high (n = 4 groups) and low (n = 5 groups) income
      pregnant women aged 18-35 years to discuss health, GWG, diet and physical
      activity following a discussion guide. The constant comparative method was used
      to code focus group notes and to identify emergent themes. Themes were
      categorized within the integrative model of behavioral prediction. Low income
      women, in contrast to high income women, had higher BMIs, had more children, and
      were African American. Diet and physical activity behaviors reported by low
      income women were more likely to promote positive energy balance than were those
      of high income women. The underlying behavioral, efficacy, and normative beliefs
      described by both groups of women explained most of these behaviors. Experiencing
      multiple risk factors may lead to (1) engaging in several behavior changes during
      pregnancy unrelated to weight and (2) holding more weight gain-promoting beliefs
      than weight maintaining beliefs. These factors could inhibit diet and physical
      activity behaviors and/or behavior changes that promote energy balance and in
      combination, result in excessive GWG. Low income women experience multiple risk
      factors for excessive GWG and successful interventions to prevent excessive GWG
      and pregnancy related weight gain will need to recognize the complex web of
      influences.

PMID- 22415813
TI  - Assessing the congruence of transition preparedness as reported by parents and
      their adolescents with special health care needs.
AB  - Several studies have investigated how prepared adolescents are to transition to
      adult health care and barriers to transition for adolescents with special health
      care needs. The majority of these studies, however, have only assessed these
      experiences from the parents' point of view. Our study aims to assess the
      congruence of adolescents and parents reported transition planning and the
      factors associated with planning. A secondary data analysis was conducted using
      telephone survey data. Data were collected from parents and adolescents with
      special health care needs who received health care through Florida's Title V
      public insurance program. The final sample included 376 matched pairs of
      adolescent-parent surveys. To assess health care transition planning, respondents
      were asked if discussions had occurred with the adolescents' doctor, nurse, or
      with each other. Parents reported higher levels of planning than adolescents.
      Results show the lowest level of agreement between the parent and adolescent
      reports (kappa < 0.2) and the highest level of agreement when parents and
      adolescents were asked if they discussed transition with each other (kappa =
      0.19). Regression results suggest that older adolescents are more prepared (vs.
      younger) and that adolescents whose parents have lower educational attainment are
      less prepared for transition. Results from this study suggest that there may be
      miscommunication around discussions related to transition, although further
      research is warranted. It is important to ensure that adolescents, not just
      parents, have a thorough understanding of transition since they will ultimately
      be responsible for their own health care once they reach adulthood.

PMID- 22415814
TI  - Severe acute maternal morbidity in a high-income developing multiethnic country.
AB  - With declining maternal mortality, the study of severe acute maternal morbidity
      (SAMM) provides an opportunity to measure the quality of maternal care and to
      identify ways to improve it. The objective was to study the epidemiology of
      severe acute maternal morbidity in a high income, rapidly developing, multiethnic
      country in the Middle East, and to determine the role of ethnicity in maternal
      morbidity. We included all births occurring in maternal units with more than 500
      births a year over a 6 year period in Abu Dhabi emirate, the largest province of
      the United Arab Emirates. Data on SAMM was collected retrospectively for the
      first 3 years and prospectively for the later 3 years. A clinical criteria based
      approach was used to define SAMM. Over the 6 year period there were 122,705
      deliveries, and a total of 926 cases of SAMM were identified. The SAMM to births
      ratio was 7.5/1,000 deliveries. The leading cause of maternal morbidity was
      hypertensive disorders (59.5 %) followed by hemorrhage (39.6 %). There were clear
      ethnic differences. Preeclampsia was significantly higher in women from the
      Indian sub-continent and hemorrhage was more prevalent in UAE women. We have
      shown that it is possible to use a clinical criteria based approach to study the
      epidemiology of SAMM. The leading contributors to SAMM were hypertensive
      disorders and hemorrhage with clear ethnic links supporting earlier reports of a
      complex interaction between ethnicity, socioeconomic status and maternal health.

PMID- 22415815
TI  - Positive and negative psychosocial impact of being diagnosed with cancer as an
      adolescent or young adult.
AB  - BACKGROUND: The objective of this study was to explore the psychosocial impact of
      cancer on newly diagnosed adolescent and young adult (AYA) cancer patients.
      METHODS: This was a population-based, multicenter study of 523 newly diagnosed
      AYA survivors (ages 15-39 years) of germ cell cancer (n = 204), non-Hodgkin
      lymphoma (n = 131), Hodgkin lymphoma (n = 142), acute lymphocytic leukemia (n =
      21), or sarcoma (n = 25) from 7 National Cancer Institute Surveillance,
      Epidemiology, and End Results (SEER) registries. Age at diagnosis was categorized
      into 3 groups (ages 15-20 years, 21-29 years, and 30-39 years). RESULTS:
      Respondents (43% response rate), on average (+/-standard deviation), were aged 29
      = 6.7 years, and most patients (80.1%) were not receiving treatment at the time
      the completed the survey. With modest differences between the age groups, the
      most prevalent areas of life impacted in a negative way were financial, body
      image, control over life, work plans, relationship with spouse/significant other,
      and plans for having children. Endorsement of positive life impact items also was
      evident across the 3 age groups, particularly with regard to relationships,
      future plans/goals, and health competence. CONCLUSIONS: The current results
      indicated that there will be future need for interventions targeting financial
      assistance, body image issues, relationships, and helping AYAs to attain their
      education objectives.

PMID- 22415816
TI  - Fluorescence correlation spectroscopy.
AB  - Fluorescence correlation spectroscopy (FCS) is a powerful technique to measure
      concentrations, mobilities, and interactions of fluorescent biomolecules. It can
      be applied to various biological systems such as simple homogeneous solutions,
      cells, artificial, or cellular membranes and whole organisms. Here, we introduce
      the basic principle of FCS, discuss its application to biological questions as
      well as its limitations and challenges, present an overview of novel technical
      developments to overcome those challenges, and conclude with speculations about
      the future applications of fluorescence fluctuation spectroscopy.

PMID- 22415817
TI  - Supported Pd-Cu bimetallic nanoparticles that have high activity for the
      electrochemical oxidation of methanol.
AB  - Monodisperse bimetallic Pd-Cu nanoparticles with controllable size and
      composition were synthesized by a one-step multiphase ethylene glycol (EG)
      method. Adjusting the stoichiometric ratio of the Pd and Cu precursors afforded
      nanoparticles with different compositions, such as Pd(85)-Cu(15), Pd(56)-Cu(44),
      and Pd(39)-Cu(61). The nanoparticles were separated from the solution mixture by
      extraction with non-polar solvents, such as n-hexane. Monodisperse bimetallic Pd
      Cu nanoparticles with narrow size-distribution were obtained without the need for
      a size-selection process. Capping ligands that were bound to the surface of the
      particles were removed through heat treatment when the as-prepared nanoparticles
      were loaded onto a Vulcan XC-72 carbon support. Supported bimetallic Pd-Cu
      nanoparticles showed enhanced electrocatalytic activity towards methanol
      oxidation compared with supported Pd nanoparticles that were fabricated according
      to the same EG method. For a bimetallic Pd-Cu catalyst that contained 15 % Cu,
      the activity was even comparable to the state-of-the-art commercially available
      Pt/C catalysts. A STEM-HAADF study indicated that the formation of random solid
      solution alloy structures in the bimetallic Pd(85)-Cu(15)/C catalysts played a
      key role in improving the electrochemical activity.

PMID- 22415818
TI  - Principal interactions analysis for repeated measures data: application to gene
      gene and gene-environment interactions.
AB  - Many existing cohorts with longitudinal data on environmental exposures,
      occupational history, lifestyle/ behavioral characteristics, and health outcomes
      have collected genetic data in recent years. In this paper, we consider the
      problem of modeling gene-gene and gene-environment interactions with repeated
      measures data on a quantitative trait. We review possibilities of using classical
      models proposed by Tukey (1949) and Mandel (1961) using the cell means of a two
      way classification array for such data. Although these models are effective for
      detecting interactions in the presence of main effects, they fail miserably if
      the interaction structure is misspecified. We explore a more robust class of
      interaction models that are based on a singular value decomposition of the cell
      means residual matrix after fitting the additive main effect terms. This class of
      additive main effects and multiplicative interaction models (Gollob, 1968)
      provide useful summaries for subject-specific and time-varying effects as
      represented in terms of their contribution to the leading eigenvalues of the
      interaction matrix. It also makes the interaction structure more amenable to
      geometric representation. We call this analysis 'principal interactions
      analysis'. While the paper primarily focuses on a cell-mean-based analysis of
      repeated measures outcome, we also introduce resampling-based methods that
      appropriately recognize the unbalanced and longitudinal nature of the data
      instead of reducing the response to cell means. We illustrate the proposed
      methods by using data from the Normative Aging Study, a longitudinal cohort study
      of Boston area veterans since 1963. We carry out simulation studies under an
      array of classical interaction models and common epistasis models to illustrate
      the properties of the principal interactions analysis procedure in comparison
      with the classical alternatives.

PMID- 22415819
TI  - Does quantification of myocardial flow reserve using rubidium-82 positron
      emission tomography facilitate detection of multivessel coronary artery disease?
AB  - BACKGROUND: Relative myocardial perfusion imaging (MPI) is the standard imaging
      approach for the diagnosis and prognostic work-up of coronary artery disease
      (CAD). However, this technique may underestimate the extent of disease in
      patients with 3-vessel CAD. Positron emission tomography (PET) is also able to
      quantify myocardial blood flow. Rubidium-82 ((82)Rb) is a valid PET tracer
      alternative in centers that lack a cyclotron. The aim of this study was to assess
      whether assessment of myocardial flow reserve (MFR) measured with (82)Rb PET is
      an independent predictor of severe obstructive 3-vessel CAD. METHODS: We enrolled
      a cohort of 120 consecutive patients referred to a dipyridamole (82)Rb PET MPI
      for evaluation of ischemia neither with prior coronary artery bypass graft nor
      with recent percutaneous coronary intervention that also underwent coronary
      angiogram within 6 months of the PET study. Patients with and without 3-vessel
      CAD were compared. RESULTS: Among patients with severe 3-vessel CAD, MFR was
      globally reduced (<2) in 88% (22/25). On the adjusted logistic Cox model, MFR was
      an independent predictor of 3-vessel CAD [.5 unit decrease, HR: 2.1, 95% CI (1.2
      3.8); P = .015]. The incremental value of (82)Rb MFR over the SSS was also shown
      by comparing the adjusted SSS models with and without (82)Rb MFR (P = .005).
      CONCLUSION: (82)Rb MFR is an independent predictor of 3-vessel CAD and provided
      added value to relative MPI. Clinical integration of this approach should be
      considered to enhance detection and risk assessment of patients with known or
      suspected CAD.

PMID- 22415820
TI  - Focal breast uptake of 99mTc-sestamibi in a man with spindle cell lipoma.

PMID- 22415821
TI  - A tribute to Francesco Lenci on the occasion of his 70th birthday.

PMID- 22415823
TI  - Observation of conducting filament growth in nanoscale resistive memories.
AB  - Nanoscale resistive switching devices, sometimes termed memristors, have recently
      generated significant interest for memory, logic and neuromorphic applications.
      Resistive switching effects in dielectric-based devices are normally assumed to
      be caused by conducting filament formation across the electrodes, but the nature
      of the filaments and their growth dynamics remain controversial. Here we report
      direct transmission electron microscopy imaging, and structural and compositional
      analysis of the nanoscale conducting filaments. Through systematic ex-situ and in
      situ transmission electron microscopy studies on devices under different
      programming conditions, we found that the filament growth can be dominated by
      cation transport in the dielectric film. Unexpectedly, two different growth modes
      were observed for the first time in materials with different microstructures.
      Regardless of the growth direction, the narrowest region of the filament was
      found to be near the dielectric/inert-electrode interface in these devices,
      suggesting that this region deserves particular attention for continued device
      optimization.

PMID- 22415822
TI  - Lipid storage disorders block lysosomal trafficking by inhibiting a TRP channel
      and lysosomal calcium release.
AB  - Lysosomal lipid accumulation, defects in membrane trafficking and altered Ca(2+)
      homoeostasis are common features in many lysosomal storage diseases. Mucolipin
      transient receptor potential channel 1 (TRPML1) is the principle Ca(2+) channel
      in the lysosome. Here we show that TRPML1-mediated lysosomal Ca(2+) release,
      measured using a genetically encoded Ca(2+) indicator (GCaMP3) attached directly
      to TRPML1 and elicited by a potent membrane-permeable synthetic agonist, is
      dramatically reduced in Niemann-Pick (NP) disease cells. Sphingomyelins (SMs) are
      plasma membrane lipids that undergo sphingomyelinase (SMase)-mediated hydrolysis
      in the lysosomes of normal cells, but accumulate distinctively in lysosomes of NP
      cells. Patch-clamp analyses revealed that TRPML1 channel activity is inhibited by
      SMs, but potentiated by SMases. In NP-type C cells, increasing TRPML1's
      expression or activity was sufficient to correct the trafficking defects and
      reduce lysosome storage and cholesterol accumulation. We propose that abnormal
      accumulation of luminal lipids causes secondary lysosome storage by blocking
      TRPML1- and Ca(2+)-dependent lysosomal trafficking.

PMID- 22415824
TI  - SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal
      single-strand break repair.
AB  - Breaking and sealing one strand of DNA is an inherent feature of chromosome
      metabolism to overcome torsional barriers. Failure to reseal broken DNA strands
      results in protein-linked DNA breaks, causing neurodegeneration in humans. This
      is typified by defects in tyrosyl DNA phosphodiesterase 1 (TDP1), which removes
      stalled topoisomerase 1 peptides from DNA termini. Here we show that TDP1 is a
      substrate for modification by the small ubiquitin-like modifier SUMO. We purify
      SUMOylated TDP1 from mammalian cells and identify the SUMOylation site as lysine
      111. While SUMOylation exhibits no impact on TDP1 catalytic activity, it promotes
      its accumulation at sites of DNA damage. A TDP1 SUMOylation-deficient mutant
      displays a reduced rate of repair of chromosomal single-strand breaks arising
      from transcription-associated topoisomerase 1 activity or oxidative stress. These
      data identify a role for SUMO during single-strand break repair, and suggest a
      mechanism for protecting the nervous system from genotoxic stress.

PMID- 22415825
TI  - Probing charge scattering mechanisms in suspended graphene by varying its
      dielectric environment.
AB  - Graphene with high carrier mobility MU is required both for graphene-based
      electronic devices and for the investigation of the fundamental properties of
      Dirac fermions. An attractive approach to increase the mobility is to place
      graphene in an environment with high static dielectric constant kappa that would
      screen the electric field due to the charged impurities present near graphene's
      surface. Here we investigate the effect of the dielectric environment of graphene
      and study electrical transport in multi-terminal graphene devices suspended in
      liquids with kappa ranging from 1.9 to 33. For non-polar liquids (kappa<5), we
      observe a rapid increase of MU(kappa), with room-temperature mobility reaching
      ~60,000 cm(2) Vs(-1) for devices in anisole (kappa = 4.3). We associate this
      trend with dielectric screening of charged impurities adsorbed on graphene. We
      observe much lower mobility MU~20,000 cm(2) Vs(-1) for devices in polar liquids
      (kappa >= 18) and explain it by additional scattering caused by ions present in
      such liquids.

PMID- 22415826
TI  - Activation of canonical Wnt signalling is required for TGF-beta-mediated
      fibrosis.
AB  - The transforming growth factor-beta (TGF-beta) signalling pathway is a key
      mediator of fibroblast activation that drives the aberrant synthesis of
      extracellular matrix in fibrotic diseases. Here we demonstrate a novel link
      between transforming growth factor-beta and the canonical Wnt pathway. TGF-beta
      stimulates canonical Wnt signalling in a p38-dependent manner by decreasing the
      expression of the Wnt antagonist Dickkopf-1. Tissue samples from human fibrotic
      diseases show enhanced expression of Wnt proteins and decreased expression of
      Dickkopf-1. Activation of the canonical Wnt pathway stimulates fibroblasts in
      vitro and induces fibrosis in vivo. Transgenic overexpression of Dickkopf-1
      ameliorates skin fibrosis induced by constitutively active TGF-beta receptor type
      I signalling and also prevents fibrosis in other TGF-beta-dependent animal
      models. These findings demonstrate that canonical Wnt signalling is necessary for
      TGF-beta-mediated fibrosis and highlight a key role for the interaction of both
      pathways in the pathogenesis of fibrotic diseases.

PMID- 22415827
TI  - Infrared light excites cells by changing their electrical capacitance.
AB  - Optical stimulation has enabled important advances in the study of brain function
      and other biological processes, and holds promise for medical applications
      ranging from hearing restoration to cardiac pace making. In particular, pulsed
      laser stimulation using infrared wavelengths >1.5 MUm has therapeutic potential
      based on its ability to directly stimulate nerves and muscles without any genetic
      or chemical pre-treatment. However, the mechanism of infrared stimulation has
      been a mystery, hindering its path to the clinic. Here we show that infrared
      light excites cells through a novel, highly general electrostatic mechanism.
      Infrared pulses are absorbed by water, producing a rapid local increase in
      temperature. This heating reversibly alters the electrical capacitance of the
      plasma membrane, depolarizing the target cell. This mechanism is fully reversible
      and requires only the most basic properties of cell membranes. Our findings
      underscore the generality of pulsed infrared stimulation and its medical
      potential.

PMID- 22415828
TI  - Bright single-photon sources in bottom-up tailored nanowires.
AB  - The ability to achieve near-unity light-extraction efficiency is necessary for a
      truly deterministic single-photon source. The most promising method to reach such
      high efficiencies is based on embedding single-photon emitters in tapered
      photonic waveguides defined by top-down etching techniques. However, light
      extraction efficiencies in current top-down approaches are limited by fabrication
      imperfections and etching-induced defects. The efficiency is further tempered by
      randomly positioned off-axis quantum emitters. Here we present perfectly
      positioned single quantum dots on the axis of a tailored nanowire waveguide using
      bottom-up growth. In comparison to quantum dots in nanowires without waveguides,
      we demonstrate a 24-fold enhancement in the single-photon flux, corresponding to
      a light-extraction efficiency of 42%. Such high efficiencies in one-dimensional
      nanowires are promising to transfer quantum information over large distances
      between remote stationary qubits using flying qubits within the same nanowire p-n
      junction.

PMID- 22415829
TI  - Intracellular chloride concentration influences the GABAA receptor subunit
      composition.
AB  - GABA(A) receptors (GABA(A)Rs) exist as different subtype variants showing unique
      functional properties and defined spatio-temporal expression pattern. The
      molecular mechanisms underlying the developmental expression of different
      GABA(A)R are largely unknown. The intracellular concentration of chloride ([Cl(
      )](i)), the main ion permeating through GABA(A)Rs, also undergoes considerable
      changes during maturation, being higher at early neuronal stages with respect to
      adult neurons. Here we investigate the possibility that [Cl(-)](i) could modulate
      the sequential expression of specific GABA(A)Rs subtypes in primary cerebellar
      neurons. We show that [Cl(-)](i) regulates the expression of alpha3-1 and delta
      containing GABA(A) receptors, responsible for phasic and tonic inhibition,
      respectively. Our findings highlight the role of [Cl(-)](i) in tuning the
      strength of GABAergic responses by acting as an intracellular messenger.

PMID- 22415830
TI  - Odour concentration-dependent olfactory preference change in C. elegans.
AB  - The same odorant can induce attractive or repulsive responses depending on its
      concentration in various animals including humans. However, little is understood
      about the neuronal basis of this behavioural phenomenon. Here we show that
      Caenorhabditis elegans avoids high concentrations of odorants that are attractive
      at low concentrations. Behavioural analyses and computer simulation reveal that
      the odour concentration-dependent behaviour is primarily generated by
      klinokinesis, a behavioural strategy in C. elegans. Genetic analyses and lesion
      experiments show that distinct combinations of sensory neurons function at
      different concentrations of the odorant; AWC and ASH sensory neurons have
      critical roles for attraction to or avoidance of the odorant, respectively.
      Moreover, we found that AWC neurons respond to only lower concentrations of the
      odorant, whereas ASH neurons respond to only higher concentrations of odorant.
      Hence, our study suggests that odour concentration coding in C. elegans mostly
      conforms to the labelled-line principle where distinct neurons respond to
      distinct stimuli.

PMID- 22415831
TI  - Multiple exposures to drought 'train' transcriptional responses in Arabidopsis.
AB  - Pre-exposure to stress may alter plants' subsequent responses by producing faster
      and/or stronger reactions implying that plants exercise a form of 'stress
      memory'. The mechanisms of plants' stress memory responses are poorly understood
      leaving this fundamental biological question unanswered. Here we show that during
      recurring dehydration stresses Arabidopsis plants display transcriptional stress
      memory demonstrated by an increase in the rate of transcription and elevated
      transcript levels of a subset of the stress-response genes (trainable genes).
      During recovery (watered) states, trainable genes produce transcripts at basal
      (preinduced) levels, but remain associated with atypically high H3K4me3 and Ser5P
      polymerase II levels, indicating that RNA polymerase II is stalled. This is the
      first example of a stalled RNA polymerase II and its involvement in
      transcriptional memory in plants. These newly discovered phenomena might be a
      general feature of plant stress-response systems and could lead to novel
      approaches for increasing the flexibility of a plant's ability to respond to the
      environment.

PMID- 22415832
TI  - Fast and ultrasensitive method for quantitating prion infectivity titre.
AB  - Bioassay by end-point dilution has been used for decades for routine
      determination of prion infectivity titre. Here we show that the new protein
      misfolding cyclic amplification with beads (PMCAb) technique can be used to
      estimate titres of the infection-specific forms of the prion protein with a
      higher level of precision and in 3-6 days as opposed to 2 years, when compared
      with the bioassay. For two hamster strains, 263 K and SSLOW, the median reactive
      doses determined by PCMAb (PMCAb(50)) were found to be 10(12.8) and 10(12.2) per
      gram of brain tissue, which are 160- and 4,000-fold higher than the corresponding
      median infectious dose (ID(50)) values measured by bioassay. The 10(2)- to 10(3)
      fold differences between ID(50) and PMCAb(50) values could be due to a large
      excess of PMCAb-reactive prion protein seeds with little or no infectivity.
      Alternatively, the differences between ID(50) and PMCAb(50) could be due to
      higher rate of clearance of infection-specific prion protein seeds in animals
      versus PMCAb reactions. A well-calibrated PMCAb reaction can be an efficient and
      cost-effective method for the estimation of infection-specific prion protein
      titre.

PMID- 22415833
TI  - Integrated photosystem II-based photo-bioelectrochemical cells.
AB  - Photosynthesis is a sustainable process that converts light energy into chemical
      energy. Substantial research efforts are directed towards the application of the
      photosynthetic reaction centres, photosystems I and II, as active components for
      the light-induced generation of electrical power or fuel products. Nonetheless,
      no integrated photo-bioelectrochemical device that produces electrical power,
      upon irradiation of an aqueous solution that includes two inter-connected
      electrodes is known. Here we report the assembly of photobiofuel cells that
      generate electricity upon irradiation of biomaterial-functionalized electrodes in
      aqueous solutions. The cells are composed of electrically contacted photosystem
      II-functionalized photoanodes and an electrically wired bilirubin oxidase/carbon
      nanotubes-modified cathode. Illumination of the photoanodes yields the oxidation
      of water to O(2) and the transfer of electrons through the external circuit to
      the cathode, where O(2) is re-reduced to water.

PMID- 22415834
TI  - Sensitivity control through attenuation of signal transfer efficiency by negative
      regulation of cellular signalling.
AB  - Sensitivity is one of the hallmarks of biological and pharmacological responses.
      However, the principle of controlling sensitivity remains unclear. Here we
      theoretically analyse a simple biochemical reaction and find that the signal
      transfer efficiency of the transient peak amplitude attenuates depending on the
      strength of negative regulation. We experimentally find that many signalling
      pathways in various cell lines, including the Akt and ERK pathways, can be
      approximated by simple biochemical reactions and that the same property of the
      attenuation of signal transfer efficiency was observed for such pathways. Because
      of this property, a downstream molecule should show higher sensitivity to an
      activator and lower sensitivity to an inhibitor than an upstream molecule.
      Indeed, we experimentally verify that S6, which lies downstream of Akt, shows
      lower sensitivity to an epidermal growth factor receptor inhibitor than Akt.
      Thus, cells can control downstream sensitivity through the attenuation of signal
      transfer efficiency by changing the expression level of negative regulators.

PMID- 22415835
TI  - Ciliogenic RFX transcription factors regulate FGF1 gene promoter.
AB  - Fibroblast growth factor 1 (FGF1) has been shown to regulate cell proliferation,
      cell division, and neurogenesis. Human FGF1 gene 1B promoter (-540 to +31)-driven
      green fluorescence (F1BGFP) was shown to recapitulate endogenous FGF1 gene
      expression. It can also be used to isolate neural stem/progenitor cells (NSPCs)
      and glioblastoma stem cells (GBM-SCs) from developing mouse brains and human
      glioblastoma tissues, respectively. However, the regulatory mechanisms of FGF-1B
      promoter and F1BGFP(+) cells are not clear. In this study, we present several
      lines of evidence to show the roles of ciliogenic RFX transcription factors in
      the regulation of FGF-1B gene promoter and F1BGFP(+) cells: (i) RFX1, RFX2, and
      RFX3 transcription factors could directly bind the 18-bp cis-element (-484 to 
      467), and contribute to the regulation of FGF1 promoter and neurosphere
      formation. (ii) We demonstrated RFX2/RFX3 complex could only be detected in the
      nuclear extract of FGF-1B positive cells, but not in FGF-1B negative cells. (iii)
      Protein kinase C inhibitors, staurosporine and rottlerin, could decrease the
      percentage of F1BGFP(+) cells and their neurosphere formation efficiency through
      reducing the RFX2/3 complex. (iv) RNA interference knockdown of RFX2 could
      significantly reduce the percentage of F1BGFP(+) cells and their neurosphere
      formation efficiency whereas overexpression of RFX2 resulted in the opposite
      effects. Taken together, this study suggests ciliogenic RFX transcription factors
      regulate FGF-1B promoter activity and the maintenance of F1BGFP(+) NSPCs and GBM
      SCs.

PMID- 22415836
TI  - High-throughput screening assay for embryoid body differentiation of human
      embryonic stem cells.
AB  - Serum-free human pluripotent stem cell media offer the potential to develop
      reproducible clinically applicable differentiation strategies and protocols. The
      vast array of possible growth factor and cytokine combinations for media
      formulations makes differentiation protocol optimization both labor and cost
      intensive. This unit describes a 96-well plate, 4-color flow cytometry-based
      screening assay to optimize pluripotent stem cell differentiation protocols. We
      provide conditions both to differentiate human embryonic stem cells (hESCs) into
      the three primary germ layers, ectoderm, endoderm, and mesoderm, and to utilize
      flow cytometry to distinguish between them. This assay exhibits low inter-well
      variability and can be utilized to efficiently screen a variety of media
      formulations, reducing cost, incubator space, and labor. Protocols can be adapted
      to a variety of differentiation stages and lineages.

PMID- 22415837
TI  - A protocol to quantify mammary early common progenitors from long-term
      mammosphere culture.
AB  - Here we describe a protocol established in our laboratory to quantify early
      common progenitors/stem cells grown as spheres in non-adherent culture
      conditions. This protocol is based on the combination of two functional tests:
      the mammosphere assay to maintain and enrich early mammary progenitors/stem
      cells, and the epithelial colony-forming cells (E-CFC) assay to identify and
      quantify further differentiated epithelial progenitors. Primary spheres mainly
      contain progenitors and rare stem/early common progenitor cells while secondary
      and tertiary spheres contain progenitor cells derived from the early common
      progenitor/stem cell population maintained through passages and partially
      differentiated. Spheres are enzymatically and mechanically dissociated; the
      derived cells are subsequently plated on irradiated NIH-3T3 fibroblasts for
      further processing, as in the E-CFC assay. The principle of this assay is to
      quantify the number of epithelial colonies generated by cells present in the
      different sequential spheres. This assay has therefore been named ECP-DC,
      standing for Early Common Progenitor-Derived Colonies assay.

PMID- 22415838
TI  - Amniotic membrane: separation of amniotic mesoderm from amniotic epithelium and
      isolation of their respective mesenchymal stromal and epithelial cells.
AB  - The human amniotic membrane (hAM) or amnion contains two principal types of
      cells: amniotic epithelial cells (hAECs) and amniotic mesenchymal stromal cells
      (hAMSCs), located in two distinct regions: the epithelium and the stromal layer.
      Emerging evidence suggests that both of them retain multipotent/pluripotent
      characteristics, making the amniotic membrane a promising and very attractive
      source of cells for regenerative medicine. Therefore, the isolation of hAECs and
      hAMSCs has recently received great interest; they can be released by differential
      enzymatic digestion and various procedures have been reported; however,
      significant contamination of hAMCs with hAECs and vice versa frequently occurs.
      This unit describes an efficient and rapid method to separate, mechanically,
      amniotic mesoderm from amniotic epithelium in order to obtain, after subsequent
      enzymatic digestions, purified population of hAMCs and hAECs. In this way, the
      cells can be cultured or investigated for other aims avoiding additional
      procedures related to their purification.

PMID- 22415839
TI  - Derivation of cerebellar neurons from human pluripotent stem cells.
AB  - Here we provide a protocol for differentiation of human embryonic stem cells
      (hESC) into cerebellar neurons using a novel defined culture method. This
      protocol is based on the application of inductive signaling factors involved in
      the early patterning of the cerebellar region of the neural tube, followed by the
      application of factors responsible for cerebellar neuron specification. Human
      pluripotent stem cells are induced to form spherical embryonic-like structures
      called embryoid bodies (EBs) and neuroepithelial tube-like rosettes using defined
      chemical conditions. In the presence of FGF, Wnt, and RA signaling factors the
      rosettes were specified to OTX2-expressing cells. Further specification of
      derived cells involves application of BMP factors involved in early development
      of granule cell progenitors, followed by mitogens and neurotrophins. It typically
      takes 5 weeks to generate the functional cerebellar granule neurons. This
      protocol is feeder-free, applies human recombinant factors, and produces high
      yield of desired neurons.

PMID- 22415840
TI  - Reproducible expansion and characterization of mouse neural stem/progenitor cells
      in adherent cultures derived from the adult subventricular zone.
AB  - Endogenous neural stem/progenitor cells (NSPCs) residing in the subventricular
      zone (SVZ) of the adult mouse forebrain have been shown to enhance their
      neurogenic potential in response to CNS injury. Mechanisms involved in regulating
      adult neurogenesis under naive or stressed conditions can be studied using a
      monolayer cell-culture system of the nestin-expressing NSPC lineage to analyze
      proliferation, survival, and differentiation. Here, a protocol for the expansion
      of NSPCs for studies aimed at understanding the functional role of NSPCs in
      maintaining adult neurogenic processes is described. This unit outlines detailed
      procedures for: (1) isolation, maintenance, and culture of the NSPC component of
      the SVZ niche from the lateral wall of the lateral ventricle; (2)
      characterization of NSPC functions by examining proliferation, survival, and
      differentiation; and (3) efficient siRNA transfection methods in 96-well format.

PMID- 22415841
TI  - Neural differentiation of P19 carcinoma cells and primary neurospheres: cell
      morphology, proliferation, viability, and functionality.
AB  - This unit describes the culture and induction of in vitro models of neural
      differentiation and strategies to evaluate the participation of extrinsic and
      intrinsic factors in modulation of this process. Protocols focus on large-scale
      expansion of pluripotent P19 murine embryonic carcinoma cells and their induction
      to neural differentiation in the presence of retinoic acid, closely resembling
      conditions of early neuroectodermal differentiation. Procedures are also
      described for obtaining rat neural precursor cells (NPCs) or neurospheres and for
      differentiating them in the absence of growth factors. Experimental strategies
      are reported using P19 cells and NPCs as in vitro models for studying the actions
      of extrinsic and intrinsic factors on morphology, proliferation, viability,
      neural phenotype determination, and progress of differentiation, as well as the
      functionality of ion channels and metabotropic receptors in inducing calcium
      fluxes at different developmental stages. The methods described here may be
      useful for optimizing in vitro protocols for stem cell differentiation into
      defined neural populations, as well as for studying mechanisms that underlie
      neurogenesis and gliogenesis.

PMID- 22415842
TI  - Using microRNAs to enhance the generation of induced pluripotent stem cells.
AB  - Somatic cells reprogrammed to acquire an ES-like state are termed iPS cells. In
      this unit, a protocol to use microRNAs as enhancers to increase the reprogramming
      efficiency is described. Mouse embryonic fibroblasts (MEFs) are isolated from
      E13.5 mouse embryos and seeded for reprogramming by defined factors. microRNA
      mimics are transfected into MEFs at two time points during this process to
      enhance the overall reprogramming efficiency. Two standard protocols for
      characterization of these miR-iPSCs, embryoid body formation and teratoma
      formation, are also provided. By using this method, the investigators can obtain
      a significantly higher number of bona-fide iPSC colonies and miR-iPSCs can be
      derived at a faster rate than with non-treated cells.

PMID- 22415843
TI  - Detection and measurement of surface electron transfer on reduced molybdenum
      oxides (MoO(x)) and catalytic activities of Au/MoO(x).
AB  - The sensing of electrons confined inside surface defect sites has been
      demonstrated. Tetracyanoethylene was employed as a single-electron acceptor to
      characterize the reduction of fully oxidized MoO(3) . Electron transfer deposits
      negative charge on closely contacted gold nanoparticles on the surface, which
      explains the high catalytic activity in the aerobic oxidation of alcohols.

PMID- 22415844
TI  - Characteristics of atmospheric non-methane hydrocarbons during haze episode in
      Beijing, China.
AB  - This study firstly focused on non-methane hydrocarbons (NMHCs) during three
      successive days with haze episode (16-18 August 2006) in Beijing. Concentrations
      of alkanes, alkenes, aromatic hydrocarbons, and ethyne all peaked at traffic rush
      hour, implying vehicular emission; and alkanes also peaked at non-traffic rush
      hour in the daytime, implying additional source. Especially, alkanes and
      aromatics clearly showed higher levels in the nighttime than that in the daytime,
      implying their active photochemical reactions in the daytime. Correlation
      coefficients (R (2)) showed that propane, n-butane, i-butane, ethene, propene,
      and benzene correlated with ethyne (R (2) = 0.61-0.66), suggesting that their
      main source is vehicular emission; 2-methylpentane and n-hexane correlated with i
      pentane (R (2) = 0.61-0.64), suggesting that gasoline evaporation is their main
      source; and ethylbezene, m-/p-xylene, and o-xylene correlated with toluene (R (2)
      = 0.60-0.79), suggesting that their main source is similar to that of toluene
      (e.g., solvent usage). The R (2) of ethyne, i-pentane, and toluene with total
      NMHCs were 0.58, 0.76, and 0.60, respectively, indicating that ambient
      hydrocarbons are associated with vehicular emission, gasoline evaporation, and
      solvent usage. The sources of other hydrocarbons (e.g., ethane) might be natural
      gas leakage, biogenic emission, or long-range transport of air pollutants.
      Measured higher mean B/T ratio (0.78 +/- 0.27) was caused by the more intensive
      photochemical activity of toluene than benzene, still indicating the dominant
      emission from vehicles.

PMID- 22415845
TI  - Integrating data-driven ecological models in an expert-based decision support
      system for water management in the Du river basin (Vietnam).
AB  - In this study, classification trees were combined with the Water Framework
      Directive (WFD)-Explorer, a modular toolbox that supports integrated water
      management in a river basin to evaluate the impact of different restoration
      measures on river ecology. First, the WFD-Explorer toolbox analysed the effect of
      different restoration options on the abiotic river characteristics based on the
      water and substance balance embedded in the simulation environment. Based on
      these abiotic characteristics, the biological index Biological Monitoring Working
      Party for Vietnam was then predicted by classification trees that were trained on
      biological and abiotic data collected in the Du river basin in northern Vietnam.
      The ecological status of streams in the basin ranged from nearly pristine
      headwaters to severely impacted river stretches. Elimination of point sources
      from ore extraction and decentralised domestic wastewater treatment proved to be
      the most effective measures to improve the ecological condition of the Du river
      basin. The combination of the WFD-Explorer results with data-driven models
      enabled model application in a situation where expert knowledge was lacking.
      Consequently, this approach appeared promising for decision support in the
      context of river restoration and conservation management.

PMID- 22415846
TI  - Spatial assessment of soil salinity in the Harran Plain using multiple kriging
      techniques.
AB  - The Harran Plain is located in the southeastern part of Turkey and has recently
      been developed for irrigation agriculture. It already faces soil salinity
      problems causing major yield losses. Management of the problem is hindered by the
      lack of information on the extent and geography of the salinization problem. A
      survey was carried out to delineate the spatial distribution of salt-affected
      areas by randomly selecting 140 locations that were sampled at two depths (0 to
      30 and 30 to 60 cm) and analyzed for soil salinity variables: soil electrical
      conductivity (EC), soluble cations (Ca(2+,) Mg(2+), Na(+), and K(+)), soluble
      anions (SO (4) (2-) , Cl(-)), exchangeable Na(+) (me 100 g(-1)) and exchangeable
      sodium percentage. Terrain attributes (slope, topographical wetness index) were
      extracted from the digital elevation model of the study area. Variogram analyses
      after log transformation and ordinary kriging (OK) were applied to map spatial
      patterns of soil salinity variables. Multivariate geostatistical methods
      regression kriging (RK) and kriging with external drift (KED)-were used using
      elevation and soil electrical conductivity data as covariates. Performances of
      the three estimation methods (OK, RK, and KED) were compared using independent
      validation samples randomly selected from the main dataset. Soils were
      categorized into salinity classes using disjunctive kriging (DK) and ArcGIS, and
      classification accuracy was tested using the kappa statistic. Results showed that
      soil salinity variables all have skewed distribution and are poorly correlated
      with terrain indices but have strong correlations among each other. Up to 65 %
      improvement was obtained in the estimations of soil salinity variables using
      hybrid methods over OK with the best estimations obtained with RK using EC(0-30)
      as covariate. DK-ArcGIS successfully classified soil samples into different
      salinity groups with overall accuracy of 75 % and kappa of 0.55 (p < 0.001).

PMID- 22415847
TI  - Ethical aspects of participation in the database of genotypes and phenotypes of
      the National Center for Biotechnology Information: the Cancer and Leukemia Group
      B Experience.
AB  - BACKGROUND: The rapid pace of genetics research, coupled with evolving standards
      for informed consent, can create ethical challenges regarding future use of
      tissue or information from completed clinical trials. The Cancer and Leukemia
      Group B (CALGB) Oncology Cooperative Group was faced with an ethical dilemma
      regarding sharing genetic data from a completed genome-wide association study
      (GWAS) that was conducted as part of a large, multicenter breast cancer clinical
      trial with a national database: the Database of Genotypes and Phenotypes National
      Center for Biotechnology Information (dbGaP). METHODS: The CALGB Ethics Committee
      conducted a series of multidisciplinary meetings and teleconferences involving
      patient advocates, bioethicists, clinical researchers, and clinical oncologists
      to evaluate the ethical issues raised by this case and to identify lessons for
      improving informed consent to future genetics research in oncology trials.
      RESULTS: The Ethics Committee recommended that GWAS data be provided to dbGaP
      consistent with documented consent for future use of tissue among trial
      participants. Ethical issues, including adequacy of informed consent to future
      research, limitations of privacy in modern genetics research, the potential
      impact of population-based genetics research on health disparities, and recontact
      of research participants for clinical care or further research, were identified
      as major ethical considerations in this area. CONCLUSIONS: Although modern
      standards for informed consent should not prohibit research or sharing of data
      consistent with participant's intent and the public interest, there is an urgent
      need for national consensus on the appropriate use of archived tissue and
      standardized informed consent for future research among cancer clinical trial
      participants.

PMID- 22415849
TI  - Meta-analysis of complications in aortic valve replacement: comparison of
      Medtronic-Corevalve, Edwards-Sapien and surgical aortic valve replacement in
      8,536 patients.
AB  - BACKGROUND: We sought to establish the complication rates following transcatheter
      aortic valve replacement (TAVR) in the context of high risk and octogenarian
      surgical aortic valve replacement (SAVR) in the contemporary literature, and to
      critically analyze population characteristics and outcomes. METHODS: TAVR studies
      were selected from nonoverlapping series and SAVR studies for comparison if they
      met similar entry criteria. Bayesian meta-analytic methods were employed.
      RESULTS: For the 5024 TAVR and 3512 SAVR patients included in the study, TAVR
      subjects had greater baseline renal impairment (P < 0.001), a higher incidence of
      prior myocardial infarction (P = 0.032) and respiratory disease (P = 0.005) and a
      higher logistic EuroSCORE (P = 0.039). There were no significant differences
      observed in complications studied in SAVR and TAVR: 30 day mortality (9% vs 8.5%,
      P = 0.31), 1 year mortality (18.4% vs 22.8%, P = 0.65), 30 day stroke (2.4% vs
      2.6%, P = 0.72), new permanent pacemaker (5.9% vs 12.1%, P = 0.055) and dialysis
      inception (2.4% vs 4.1%, P = 0.70). We also compared demographics and outcomes
      between the two types of transcatheter valves. Apart from some variation in
      functional status, there were no significant differences at baseline with
      different TAVR designs. The only difference in complications was the need for
      pacemaker insertion, higher with the Medtronic-Corevalve than with the Edwards
      Sapien design (24.5% vs 5.9% P < 0.0001). CONCLUSIONS: Complications for elderly
      and high risk aortic stenosis patients being treated by TAVR appear comparable to
      those selected for SAVR in the real-world.

PMID- 22415848
TI  - Deep sequencing of the LRRK2 gene in 14,002 individuals reveals evidence of
      purifying selection and independent origin of the p.Arg1628Pro mutation in
      Europe.
AB  - Genetic variation in LRRK2 predisposes to Parkinson disease (PD), which underpins
      its development as a therapeutic target. Here, we aimed to identify novel
      genotype-phenotype associations that might support developing LRRK2 therapies for
      other conditions. We sequenced the 51 exons of LRRK2 in cases comprising 12
      common diseases (n = 9,582), and in 4,420 population controls. We identified 739
      single-nucleotide variants, 62% of which were observed in only one person,
      including 316 novel exonic variants. We found evidence of purifying selection for
      the LRRK2 gene and a trend suggesting that this is more pronounced in the central
      (ROC-COR-kinase) core protein domains of LRRK2 than the flanking domains.
      Population genetic analyses revealed that LRRK2 is not especially polymorphic or
      differentiated in comparison to 201 other drug target genes. Among Europeans, we
      identified 17 carriers (0.13%) of pathogenic LRRK2 mutations that were not
      significantly enriched within any disease or in those reporting a family history
      of PD. Analysis of pathogenic mutations within Europe reveals that the
      p.Arg1628Pro (c4883G>C) mutation arose independently in Europe and Asia. Taken
      together, these findings demonstrate how targeted deep sequencing can help to
      reveal fundamental characteristics of clinically important loci.

PMID- 22415850
TI  - The adult urology perspective on management of stress urinary incontinence in
      pediatric urology: ICI-RS 2011.
AB  - The modern era of patient-centered, multidisciplinary professional practice comes
      with the expectation of effective interaction between specialties dealing with
      closely related clinical areas. Interaction between adult and pediatric urology
      is generally limited in terms of training, conferences, and joint
      diagnostic/treatment algorithms. However, in the more complex cases managed by
      pediatric urologists, long-term medical input is commonly necessary. Accordingly,
      regular interaction between the relevant specialties would be beneficial for
      continuity of care of individual patients, achieving best results at transition
      to adolescence, awareness of long-term outcome of pediatric urological procedures
      and development of new surgical techniques. This article reviews the discussions
      at the 2011 International Consultation on Incontinence Research Society meeting
      in Bristol.

PMID- 22415851
TI  - Overexpression of calreticulin in pre-eclamptic placentas: effect on apoptosis,
      cell invasion and severity of pre-eclampsia.
AB  - Endoplasmic reticulum (ER) stress has recently been identified as an important
      process involved in the pathology of pre-eclampsia (PE). Calreticulin (CRT) is an
      important ER resident protein which participates in the regulation of
      intracellular Ca(2+) homeostasis, cell adhesion, and cell apoptosis. In order to
      clarify the role of this protein in normal human pregnancy and in PE, this study
      has examined the expression of CRT in pre-eclamptic placenta compared with
      control placenta. The expression of CRT mRNA and protein was elevated in the pre
      eclamptic placentas in comparison with control placentas. Furthermore, the
      expression level was related to the severity of symptoms experienced by PE
      patients. Therefore, this study aimed to identify the biological characteristics
      of the CRT gene in trophoblast cells. A CRT-expressing vector was transfected
      into the JEG-3 human choriocarcinoma cell line. Investigations showed that both
      proliferation and invasion were inhibited and apoptosis was promoted by CRT
      expression in JEG-3 cells. These data suggest that augmentation of CRT in the
      placenta may induce cell apoptosis and impair the invasion of extravillous
      trophoblast cells, thus leading to shallow placentation in PE.

PMID- 22415852
TI  - Celecoxib inhibits growth of human autosomal dominant polycystic kidney cyst
      lining epithelial cells through the VEGF/Raf/MAPK/ERK signaling pathway.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a progressive chronic
      kidney disease. To date there are no effective medicines to halt development and
      growth of cysts. In the present study, we explored novel effects of celecoxib
      (CXB), a COX-2 specific inhibitor, on primary cultures of human ADPKD cyst-lining
      epithelial cells. Primary cultures of ADPKD cyst-lining epithelial cells were
      obtained from five patients. Effects of CXB were measured by various assays to
      detect BrdU incorporation, apoptosis and proliferation in vitro. Additionally,
      effects of CXB on kidney weight, the cyst index, the fibrosis index, blood urea
      nitrogen (BUN), serum creatinine (SCr), serum 6-keto-PGF-1alpha, serum
      thromboxane-2 (TXB2) and renal PCNA expression were assessed in Han:SPRD rat, a
      well-characterized rodent model of PKD. CXB inhibited proliferation of ADPKD cyst
      lining epithelial cells, blocked the release of VEGF from the cells and induced
      extensive apoptosis in a time- and dose-dependent manner. Moreover, CXB up
      regulated the cell cycle negative regulator p21(CIP/WAF1) and the cell cycle
      positive regulator Cyclin A, blocked ERK1/2 phosphorylation, induced apoptotic
      factors (Bax and caspase-3) and reduced Bcl-2. Furthermore, CXB inhibited the
      expression of VEGFR-2 and Raf-1 in ADPKD cyst-lining epithelial cells. CXB
      markedly reduced the cyst index, the fibrosis index, leukocyte infiltration, BUN,
      SCr, serum 6-keto-PGF-1alpha, TXB2 and renal PCNA expression in Han:SPRD rat. We
      demonstrated for the first time that CXB could suppress renal cyst-lining growth
      both in vitro and in vivo in Han:SPRD rat. CXB can inhibit proliferation,
      suppress cell cycle progression, and induce apoptosis in ADPKD cyst-lining
      epithelial cells through the inhibition of the VEGF/VEGFR-2/Raf-1/MAPK/ERK
      signaling pathway.

PMID- 22415854
TI  - Synthesis of 2- and 2,7-functionalized pyrene derivatives: an application of
      selective C-H borylation.
AB  - An efficient synthetic route to 2- and 2,7-substituted pyrenes is described. The
      regiospecific direct C-H borylation of pyrene with an iridium-based catalyst,
      prepared in situ by the reaction of [{Ir(MU-OMe)cod}(2)] (cod = 1,5
      cyclooctadiene) with 4,4'-di-tert-butyl-2,2'-bipyridine, gives 2,7
      bis(Bpin)pyrene (1) and 2-(Bpin)pyrene (2, pin = OCMe(2)CMe(2)O). From 1, by
      simple derivatization strategies, we synthesized 2,7-bis(R)-pyrenes with R =
      BF(3)K (3), Br (4), OH (5), B(OH)(2) (6), and OTf (7). Using these nominally
      nucleophilic and electrophilic derivatives as coupling partners in Suzuki
      Miyaura, Sonogashira, and Buchwald-Hartwig cross-coupling reactions, we obtained
      2,7-bis(R)-pyrenes with R = (4-CO(2)C(8)H(17))C(6)H(4) (8), Ph (9), C=CPh (10),
      C=C[{4-B(Mes)(2)}C(6)H(4)] (11), C=CTMS (12), C=C[(4-NMe(2))C(6)H(4)] (14), C=CH
      (15), N(Ph)[(4-OMe)C(6)H(4)] (16), and R = OTf, R' = C=CTMS (13). Lithiation of
      4, followed by reaction with CO(2), yielded pyrene-2,7-dicarboxylic acid (17),
      whilst borylation of 2-tBu-pyrene gave 2-tBu-7-Bpin-pyrene (18) selectively. By
      similar routes (including Negishi cross-coupling reactions), monosubstituted 2-R
      pyrenes with R = BF(3)K (19), Br (20), OH (21), B(OH)(2) (22), [4
      B(Mes)(2)]C(6)H(4) (23), B(Mes)(2) (24), OTf (25), C=CPh (26), C=CTMS (27), (4
      CO(2)Me)C(6)H(4) (28), C=CH (29), C(3)H(6)CO(2)Me (30), OC(3)H(6)CO(2)Me (31),
      C(3)H(6)CO(2)H (32), OC(3)H(6)CO(2)H (33), and O(CH(2))(12)Br (34) were obtained
      from 2. These derivatives are of synthetic and photophysical interest because
      they contain donor, acceptor, and conjugated substituents. The crystal structures
      of compounds 4, 5, 7, 12, 18, 19, 21, 23, 26, and 28-31 have also been obtained
      from single-crystal X-ray diffraction data, revealing a diversity of packing
      modes, which are described in the Supporting Information. A detailed discussion
      of the structures of 1 and 2, their polymorphs, solvates, and co-crystals is
      reported separately.

PMID- 22415853
TI  - Scanning image correlation spectroscopy.
AB  - Molecular interactions are at the origin of life. How molecules get at different
      locations in the cell and how they locate their partners is a major and partially
      unresolved question in biology that is paramount to signaling. Spatio-temporal
      correlations of fluctuating fluorescently tagged molecules reveal how they move,
      interact, and bind in the different cellular compartments. Methods based on
      fluctuations represent a remarkable technical advancement in biological imaging.
      Here we discuss image analysis methods based on spatial and temporal correlation
      of fluctuations, raster image correlation spectroscopy, number and brightness,
      and spatial cross-correlations that give us information about how individual
      molecules move in cells and interact with partners at the single molecule level.
      These methods can be implemented with a standard laser scanning microscope and
      produce a cellular level spatio-temporal map of molecular interactions.

PMID- 22415855
TI  - Friedel-Crafts acylation on graphene.
AB  - There is an excitement around graphene as a promising new material for
      nanotechnological and nanoarchitectonic applications. Despite the low chemical
      reactivity of graphene, chemical functionalization remains a prominent and viable
      solution to tailor its chemical, physical, and electronic properties. Herein, we
      report the covalent functionalization of reduced graphene oxide through Friedel
      Crafts reactions under mild conditions of polyphosphoric-acid/phosphorus
      pentoxide and 4-aminobenzoic acid. Successful functionalization was confirmed by
      X-ray photoelectron spectroscopy (XPS), FTIR, and Raman spectroscopy. The success
      of the Friedel-Crafts reaction provides an important expansion of the synthetic
      "toolbox" for future modifications of graphene towards the specific needs of
      different applications.

PMID- 22415856
TI  - Lipid profiles of pediatric hematopoietic stem cell transplant survivors.
AB  - Cardiovascular disease (CVD) is the leading cause of death among adults in the
      United States. CVD pathology, including abnormal lipid levels, may begin in
      childhood. Hematopoietic stem cell transplant (HSCT) survivors have increased
      risk of abnormal lipid levels, but there is limited information in children post
      HSCT. The study aimed to describe lipid levels and identify the factors
      associated with dyslipidemia in pediatric HSCT survivors during the first 3 years
      post-HSCT. This descriptive research study used a retrospective chart review to
      assess lipid profiles among 31 pediatric HSCT patients. Mean lipid levels were
      within normal limits but contained large ranges in values. There was no
      statistically significant change over time; however, there was an increased trend
      of total cholesterol and low-density lipoprotein levels and a decreased trend of
      high-density lipoprotein levels. The majority of patients had one abnormal lipid
      level at 1 and 2 years post-HSCT. Body mass index was the only factor
      significantly associated with dyslipidemia. An awareness of dyslipidemia among
      HSCT survivors may allow for early identification and treatment of abnormal lipid
      levels.

PMID- 22415857
TI  - Health care providers' perspectives about working with parents of children with
      cancer: a qualitative study.
AB  - Research to understand the sources of stress and job satisfaction in pediatric
      oncology staff is limited. The aim of the authors' qualitative study was to
      describe the key work-related demands and rewards in relation to working closely
      with parents from the perspective of health care providers (HCPs). Semistructured
      interviews were conducted with 13 doctors, 9 nurses, 5 social workers, and 6
      child life specialists. Line-by-line, focused, and theoretical coding was used to
      establish categories and themes. Constant comparisons were used to examine the
      relationships within and across codes and categories. Interviewing continued
      until no new themes emerged. HCPs found it rewarding when they established close
      or long-term relationships with parents and to helped families through the entire
      cancer journey, including palliative care. HCPs found it challenging to work with
      complex families; with parents who are demanding, rude, or angry; with parents
      who have differing views about the treatments and palliative care; and with
      having to relay bad news to parents. Future research could explore the
      relationship between the factors that the authors have identified and burnout
      syndrome.

PMID- 22415858
TI  - Limitations of patient-associated co-morbidity model in predicting postoperative
      morbidity and mortality in pancreatic operations.
AB  - BACKGROUND: Patient-associated co-morbidities are a potential cause of
      postoperative complications. The National Surgical Quality Improvement Project
      (NSQIP) collects data on patient outcomes to provide risk-adjusted outcomes data
      to participating hospitals. However, operations which may have a high
      distribution of technically-related complications, such as pancreatic operations,
      may not be adequately assessed using such predictive models. METHODS: A combined
      data set of NSQIP Public Use files (PUF) from 2005 to 2008 was created. Using
      this database, multiple logistic regression analyses were used to generate a
      predictive model of 30-day postoperative morbidity and mortality for pancreatic
      operations and all other operations recorded in NSQIP. Receiver-operator
      characteristic curves were generated and the area under those curves (AUROC) used
      to generate a c-statistic to assess the model's discriminatory ability. Observed
      to-expected (O/E) ratios of for mortality and morbidity using not only patient
      associated co-morbidities, but operation-associated information, such as work
      relative-value units and Current Procedural Terminology codes, were generated.
      Data were analyzed in SPSS. RESULTS: In the 4-year period analyzed, there were
      7,097 complex pancreatic procedures done which were compared to 568,371
      procedures that were not. For postoperative mortality, the AUROC was less for
      pancreatic operations (0.741) compared to all other operation (0.947) and all
      other inpatient operations (0.927). Similarly for postoperative morbidity, the
      AUROC was less for pancreatic operations (0.598) compared to all other operations
      (0.764) and all other inpatient operations (0.817). However, the O/E ratios were
      similar in both groups for mortality (all other operations, 0.94 vs. pancreatic
      operations, 0.92) and morbidity (0.98 for both). CONCLUSIONS: These data imply
      that the factors used to assess postoperative mortality and morbidity may not
      completely explain postoperative outcomes in pancreatic operations. These
      procedures are technically demanding and can have morbidities not related to pre
      existing co-morbid conditions; therefore, preoperative prediction based on pre
      existing co-morbidities may have limitations in these types of operations.

PMID- 22415859
TI  - Repulsive guidance molecule B (RGMB) plays negative roles in breast cancer by
      coordinating BMP signaling.
AB  - Repulsive guidance molecules (RGMs) coordinate axon formation and iron
      homestasis. These molecules are also known as co-receptors of bone morphogenetic
      proteins (BMPs). However, the role played by RGMs in breast cancer remains
      unclear. The present study investigated the impact of RGMB on functions of breast
      cancer cells and corresponding mechanisms. RGMB was knocked down in breast cancer
      cells by way of an anti-RGMB ribozyme transgene. Knockdown of RGMB resulted in
      enhanced capacities of proliferation, adhesion, and migration in breast cancer
      cells. Further investigations demonstrated RGMB knockdown resulted in a reduced
      expression and activity of Caspase-3, accompanied with better survival in RGMB
      knockdown cells under serum starvation, which might be induced by its repression
      on MAPK JNK pathway. Up-regulations of Snai1, Twist, FAK, and Paxillin via
      enhanced Smad dependent sigaling led to increased capacities of adhesion and
      migration. Our current data firstly revealed that RGMB may act as a negative
      regulator in breast cancer through BMP signaling.

PMID- 22415860
TI  - Social tolerance in a despotic primate: co-feeding between consortship partners
      in rhesus macaques.
AB  - Food sharing among nonkin-one of the most fascinating cooperative behaviors in
      humans-is not widespread in nonhuman primates. Over the past few years, a large
      body of work has investigated the contexts in which primates cooperate and share
      food with unrelated individuals. This work has successfully demonstrated that
      species-specific differences in temperament constrain the extent to which food
      sharing emerges in experimental situations, with despotic species being less
      likely to share food than tolerant ones. However, little experimental work has
      examined the contexts that promote food sharing and cooperation within a species.
      Here, we examine whether one salient reproductive context-the consortship dyad
      can allow the necessary social tolerance for co-feeding to emerge in an extremely
      despotic species, the rhesus macaque (Macaca mulatta). We gave naturally formed
      male-female rhesus macaque pairs access to a monopolizable food site in the free
      ranging population at Cayo Santiago, Puerto Rico. Using this method, we were able
      to show that tolerated co-feeding between unrelated adults can take place in this
      despotic species. Specifically, our results show that consort pairs co-fed at the
      experimental food site more than nonconsort control pairs, leading females to
      obtain more food in this context. These results suggest that co-feeding is
      possible even in the most despotic of primate species, but perhaps only in
      contexts that specifically promote the necessary social tolerance. Researchers
      might profit from exploring whether other kinds of within-species contexts could
      also generate cooperative behaviors.

PMID- 22415862
TI  - Prognostic value of estrogen receptor alpha and progesterone receptor conversion
      in distant breast cancer metastases.
AB  - BACKGROUND: Changes in the receptor profile of primary breast cancers to their
      metastases (receptor conversion) have been described for the estrogen receptor
      alpha (ERalpha) and progesterone receptor (PR). The purpose of this study was to
      evaluate the impact of receptor conversion for ERalpha and PR on survival in a
      large group of distant non-bone breast cancer metastases. METHODS: Receptor
      conversion was studied by immunohistochemistry in a group of 233 metastatic
      breast cancer patients. Kaplan-Meier overall survival curves were plotted, and
      differences between the curves were analyzed by log-rank analysis. The additional
      prognostic value of conversion to established prognosticators was studied by Cox
      regression. RESULTS: Overall survival of patients showing conversion from
      positive to negative ERalpha or PR, or from negative to positive ERalpha or PR,
      or remaining receptor negative was comparable, and significantly worse than
      patients remaining receptor positive. ERalpha or PR receptor conversion from
      positive in the primary breast tumor to negative in distant metastases has
      independent negative prognostic value. CONCLUSIONS: ERalpha or PR receptor
      conversion from positive in the primary breast cancer to negative in distant
      metastases has negative prognostic value.

PMID- 22415861
TI  - Dietary tryptophan changes serum stress markers, enzyme activity, and ions
      concentration of wild common carp Cyprinus carpio exposed to ambient copper.
AB  - Effect of dietary tryptophan (TRP) on copper toxicity was investigated in common
      carp, Cyprinus carpio. Fish were randomly distributed into two triplicate
      treatments (control and TRP) and fed control (TRP = 3.1 g kg(-1)) or TRP (TRP =
      8.1 g kg(-1)) diets over a 2-week period. Then, both treatments were subjected to
      10 mg l(-1) copper sulfate over a 7-day period. Mortality and serum cortisol,
      glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      sodium, potassium, and chloride levels were recorded at 0, 24, 72, 120, and 168 h
      post-copper exposure. There was no mortality in the TRP group, whereas the
      control group mortality was started at 120 h post-copper exposure (21.7 +/- 7.6
      %) and reached 61.7 +/- 10.4 % at the end of the experiment. Cortisol, glucose,
      ALT, and AST levels significantly (P < 0.05) increased after copper exposure in
      both groups; however, the control group showed significantly higher levels than
      the TRP group. In both groups, sodium decreased after copper exposure and did not
      return to the pre-exposure values. Potassium levels significantly increased 24 h
      post-copper exposure in both groups and remained significantly elevated in the
      control group at 72 h, when fell to the pre-exposure values in the TRP group. No
      significant changes were observed in the chloride levels in any groups. It is
      concluded that dietary TRP is capable to increase common carp tolerance to copper
      toxicity via mitigating copper-induced stress rather than restoring gill
      dysfunction and hydromineral imbalance.

PMID- 22415864
TI  - The influence of oxygen content on the thermal activation of hematite nanowires.

PMID- 22415863
TI  - Does psychological stress affect LUT function in children? ICI-RS 2011.
AB  - AIMS: Psychological factors and LUTS are closely associated in children. 20-40%
      of children with nocturnal enuresis (NE) and 30-40% with daytime urinary
      incontinence (DUI) have a clinical psychiatric disorder, many more are
      distressed. The associations are complex and differ for each individual subtype
      of disorder, as both genetic and environmental factors can interact. The aim of
      this paper is to provide an overview and discuss possible causal associations.
      METHODS: Relevant studies are reviewed--preferably with population-based,
      representative results. RESULTS: Four basic associations are possible.
      Psychological symptoms and disorders can (1) be a consequence of LUTS and NE/DUI;
      (2) They can be induced by them; (3) Both can be due to common, shared
      etiological factors; and (4) They can co-occur by chance without causality.
      CONCLUSIONS: Due to these complex associations, a descriptive approach is
      endorsed. Both the subtype of NE/DUI and possible psychological symptoms and
      disorders need to be identified--possible causal relationships can be analyzed in
      a second step. Screening for psychological symptoms with parental behavioral
      questionnaires in all settings is recommended, as well as counselling and
      treatment if indicated.

PMID- 22415865
TI  - Genome-wide arrays: quality criteria and platforms to be used in routine
      diagnostics.
AB  - Whole-genome analysis using genome-wide arrays, also called "genomic arrays,"
      "microarrays," or "arrays," has become the first-tier diagnostic test for
      patients with developmental abnormalities and/or intellectual disabilities. In
      addition to constitutional anomalies, genomic arrays are also used to diagnose
      acquired disorders. Despite the rapid implementation of these technologies in
      diagnostic laboratories, external quality control schemes (such as CEQA, EMQN, UK
      NEQAS, and the USA QA scheme CAP) and interlaboratory comparisons show that there
      are huge differences in quality, interpretation, and reporting among
      laboratories. We offer guidance to laboratories to help assure the quality of
      array experiments and to standardize minimum detection resolution, and we also
      provide guidelines to standardize interpretation and reporting.

PMID- 22415866
TI  - Microrheology of human synovial fluid of arthritis patients studied by diffusing
      wave spectroscopy.
AB  - The viscoelastic properties of synovial fluid (SF) are critical to its functions
      of lubrication and shock-absorption of joints in human body; a change in the
      viscoelastic properties, even of only a few percents, is often concomitant with
      arthritis. In this work, the elastic modulus G '(f) and the viscous modulus G
      ''(f) of SF from patients suffering from three kinds of joint diseases, namely,
      osteoarthritis (OA), rheumatoid arthritis (RA), and gouty arthritis (GA), were
      determined as a function of frequency "f " (in the low frequency range from f ~
      0.1 to 10 Hz) by Diffusing Wave Spectroscopy (DWS) and correlated with the white
      blood cell (WBC) count. A strong correlation was observed, showing a higher WBC
      count corresponding to lower elastic and viscous moduli, G ' and G ''; further
      details depend on inflammatory vs. non-inflammatory, and on the severity of
      inflammation. Different types of arthritis lead to different degrees of
      decreasing viscoelasticity. Identical measurements were carried out with a
      commercial visco-supplementation (or artificial SF) to serve as reference. In
      general, the reduction in both G ' and G '' was most severe in the case of GA and
      least severe in the case of OA. Besides, in all cases, the reduction in G ' was
      more prominent than the reduction in G '', indicating that in general, the
      deterioration in the elasticity of SF by inflammation is more severe than that in
      the viscosity. This simple method for quantitative physical characterization of
      synovial fluid may serve as a useful complementary metric to the conventional
      biochemical analysis in clinical diagnosis of arthritis.

PMID- 22415867
TI  - Racial and ethnic differences in cardio-metabolic risk in individuals with
      undiagnosed diabetes: National Health and Nutrition Examination Survey 1999-2008.
AB  - BACKGROUND: Although early recognition and treatment of diabetes may be essential
      to prevent complications, roughly one-fifth of diabetes remains undiagnosed.
      OBJECTIVE: Examine cardio-metabolic risk factors and their control in non
      Hispanic white (NHW), non-Hispanic black (NHB) and Mexican American (MA)
      individuals with undiagnosed diabetes. DESIGN: Nationally representative cross
      sectional study of participants in the National Health and Nutrition Examination
      Survey (NHANES) continuous cycles conducted 1999 through 2008. PARTICIPANTS: Of
      22,621 non-pregnant individuals aged >=20 years, 2521 had diagnosed diabetes. Of
      the remaining 20,100 individuals, 17,963 had HbA1c measured, 551 of whom were
      classified as having undiagnosed diabetes and comprise the study population. MAIN
      MEASURES: Undiagnosed diabetes was defined as HbA1c >= 6.5% without a self-report
      of physician diagnosed diabetes. Cardio-metabolic risk factor control was
      examined using regression methods for complex survey data. KEY RESULTS: Among
      individuals with undiagnosed diabetes, mean HbA1c level was 7.7% (95% CI: 7.5,
      7.9), 19.3% (95% CI: 14.2, 24.3) smoked, 59.7% (95% CI: 54.5, 64.8%) had
      hypertension and 96.5% (95% CI: 94.6, 98.4%) had dyslipidemia. Lipid profiles
      were remarkably different across racial-ethnic groups: NHB had the highest LDL-
      and HDL-cholesterol, but the lowest triglycerides, while MA had the highest
      triglycerides and the lowest LDL-cholesterol. After adjusting for age, sex,
      NHANES examination cycle and use of either blood pressure or lipid medication,
      the odds of having blood pressure >=130/80 mmHg was higher in NHB [1.92 (95% CI:
      1.09, 3.55)] than NHW, while the odds of having LDL-cholesterol >100 mg/dl was
      higher in NHW[2.93 (95% CI: 1.37, 6.24)] and NHB[3.34 (95% CI: 1.08, 10.3)] than
      MA. CONCLUSIONS: In a nationally representative sample of individuals with
      undiagnosed diabetes, cardio-metabolic risk factor levels were high across all
      racial/ethnic groups, but NHB and MA had poorer control compared to NHW.
      Interventions that target identification of diabetes and treatment of cardio
      metabolic risk factors are needed.

PMID- 22415869
TI  - Characterisation of solute mobility in hypercross-linked resins in solvents of
      different polarity: two promising supports for catalysis.
AB  - Two hypercross-linked resins stemming from a gel-type poly-chloromethylated
      styrene-divinylbenzene resin (GT) in beaded form are investigated with a
      combination of spectroscopic techniques (EPR and time-domain (TD)-NMR
      spectroscopy) to evaluate their use as supports for the development of
      operationally flexible heterogeneous metal catalysts, suitable to be employed in
      liquid and gas phase. The first resin (HGT) is the direct product of the
      hypercross-linking reaction, whereas the second one (HGS) is the sulphonated
      analogue of HGT obtained by exchanging approximately 3 wt % of the chloromethyl
      groups with sulphonic groups. HGT and HGS absorb both polar and apolar solvents
      in the permanent nanoporosity created by the hypercross-linking, and NMR data
      highlight that the pore size is not affected by the different properties of the
      investigated liquid media. The EPR analysis of the dry resins reveals that during
      the hypercross-linking process paramagnetic species are formed in the HGT beads,
      which persist in the sulphonated resin. The mobility of solutes inside the
      polymers framework was investigated with EPR spectroscopy upon soaking the resins
      with solutions of two spin probes (2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)
      and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL)) in THF, toluene, n
      heptane and water. The EPR spectra show that, depending on the solvent, the two
      resins can act as sorbents, able to trap the solutes in the polymer framework, or
      as simple supports that allow free diffusion of the solutes. Our results suggest
      that HGT and HGS are promising supporting materials for metal catalysts, provided
      one chooses carefully the solvent to be employed for the catalysed reaction as
      this choice strongly affects the mobility of the substrates and, thus their
      effective reactivity.

PMID- 22415868
TI  - Image analysis in fluorescence microscopy: bacterial dynamics as a case study.
AB  - Fluorescence microscopy is the primary tool for studying complex processes inside
      individual living cells. Technical advances in both molecular biology and
      microscopy have made it possible to image cells from many genetic and
      environmental backgrounds. These images contain a vast amount of information,
      which is often hidden behind various sources of noise, convoluted with other
      information and stochastic in nature. Accessing the desired biological
      information therefore requires new tools of computational image analysis and
      modeling. Here, we review some of the recent advances in computational analysis
      of images obtained from fluorescence microscopy, focusing on bacterial systems.
      We emphasize techniques that are readily available to molecular and cell
      biologists but also point out examples where problem-specific image analyses are
      necessary. Thus, image analysis is not only a toolkit to be applied to new images
      but also an integral part of the design and implementation of a microscopy
      experiment.

PMID- 22415870
TI  - A convenient formula for sample size calculations in clinical trials with
      multiple co-primary continuous endpoints.
AB  - The clinical efficacy of a new treatment may often be better evaluated by two or
      more co-primary endpoints. Recently, in pharmaceutical drug development, there
      has been increasing discussion regarding establishing statistically significant
      favorable results on more than one endpoint in comparisons between treatments,
      which is referred to as a problem of multiple co-primary endpoints. Several
      methods have been proposed for calculating the sample size required to design a
      trial with multiple co-primary correlated endpoints. However, because these
      methods require users to have considerable mathematical sophistication and
      knowledge of programming techniques, their application and spread may be
      restricted in practice. To improve the convenience of these methods, in this
      paper, we provide a useful formula with accompanying numerical tables for sample
      size calculations to design clinical trials with two treatments, where the
      efficacy of a new treatment is demonstrated on continuous co-primary endpoints.
      In addition, we provide some examples to illustrate the sample size calculations
      made using the formula. Using the formula and the tables, which can be read
      according to the patterns of correlations and effect size ratios expected in
      multiple co-primary endpoints, makes it convenient to evaluate the required
      sample size promptly.

PMID- 22415871
TI  - Efficient use of longitudinal CD4 counts and viral load measures in survival
      analysis.
AB  - CD4 counts and viral loads are dynamic quantities that change with time in HIV
      infected persons. Commonly used single summary measures, such as viral load set
      point or early CD4 count, do not explicitly account for changes in viral load or
      CD4 counts or other features of the overall time course of these measures.
      However, the efficient use of all repeated measurements within each subject is
      often a challenge made more difficult by sparse and irregular sampling over time.
      Here, we illustrate how functional principal component (FPC) analysis provides an
      effective statistical approach for exploiting the patterns in CD4 count and viral
      load data over time. We demonstrate the method by using data from Kenyan women
      who acquired HIV-1 during follow-up in a cohort that practices high-risk
      activities and were subsequently followed up prospectively from early infection.
      The FPC scores for each woman obtained using this method served as informative
      summary statistics for the CD4 count and viral load trajectories. Similar to
      baseline CD4 count or viral set point, the first FPC score can be interpreted as
      a single-value summary measure of an individual's overall CD4 count or viral
      load. However, unlike most single-value summaries of CD4 count or viral load
      trajectories, the first FPC score summarizes the dynamics of these quantities and
      is seen to reveal specific features of the trajectories associated with mortality
      in this cohort. Moreover, the FPC scores are shown to be a more powerful
      prognostic factor than other common summaries when used in survival analysis.

PMID- 22415872
TI  - Diabetes disrupts the response of retinal endothelial cells to the angiomodulator
      lysophosphatidic acid.
AB  - The objectives of this study were to investigate how diabetes mellitus (DM)
      influences responsiveness of retinal neovessels to lysophosphatidic acid (LPA)
      and to elucidate the underlying mechanism. To this end, we used an ex vivo assay
      in which neovessels sprouted from retinal explants (isolated from either control
      or DM mice) when cultured between two layers of collagen and in the presence of
      vascular endothelial growth factor-A. While DM had no effect on the formation of
      neovessels, it prevented LPA-induced regression. High-glucose (HG) treatment of
      retinal explants mimicked the DM phenotype. Similarly, primary retinal
      endothelial cells (RECs), which were subjected to HG treatment, organized into
      tubes that were resistant to LPA. HG caused LPA resistance within RECs by
      elevating ROS, which activated Src-family kinases that stimulated the
      extracellular signal-related kinase (Erk) pathway, which antagonized LPA-mediated
      signaling events that were required for regression. This ROS/Src/Erk pathway
      mechanism appeared to be the same route by which DM induced LPA resistance of
      retinal neovessels. We conclude that DM/HG reprograms signaling pathways in RECs
      to induce a state of LPA resistance.

PMID- 22415873
TI  - Liver X receptor alpha is involved in the transcriptional regulation of the 6
      phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene.
AB  - The activity of 6-phosphofructo-1-kinase is strictly controlled by fructose-2,6
      bisphosphate, the level of which is regulated by another enzyme, 6-phosphofructo
      2-kinase/fructose-2,6-bisphosphatase (PFK2/FBP2). PFK2/FBP2 is a bifunctional
      enzyme, having kinase and phosphatase activities, and regulates both glycolysis
      and gluconeogenesis. Here, we examined the hormonal regulation of the PFK2/FBP2
      gene in vitro using the reporter assay, the electromobility shift assay (EMSA),
      and the chromatin immunoprecipitation (ChIP) assay in HuH7 cells and also using
      the mouse liver in vivo. We found that the transcriptional activity of the
      PFK2/FBP2 gene was stimulated by insulin and inhibited by cAMP and
      glucocorticoid. Liver X receptor (LXR) alpha showed a potent and specific
      stimulatory effect on PFK2/FBP2 gene transcription. Deletion and mutagenesis
      analyses identified the LXR response element (LXRE) in the 5'-promoter region of
      the PFK2/FBP2 gene. Binding of LXRalpha was confirmed by the EMSA and ChIP assay.
      Endogenous PFK2/FBP2 mRNA in the mouse liver was increased in the
      fasting/refeeding state compared with the fasting state. Altogether, PFK2/FBP2
      gene transcription is found to be regulated in a way that is more similar to
      other glycolytic enzyme genes than to gluconeogenic genes. Furthermore, our data
      strongly suggest that LXRalpha is one of the key regulators of PFK2/FBP2 gene
      transcription.

PMID- 22415874
TI  - alpha1-Acid glycoprotein decreases neutrophil migration and increases
      susceptibility to sepsis in diabetic mice.
AB  - The mechanisms underlying immune deficiency in diabetes are largely unknown. In
      the present study, we demonstrate that diabetic mice are highly susceptible to
      polymicrobial sepsis due to reduction in rolling, adhesion, and migration of
      leukocytes to the focus of infection. In addition, after sepsis induction, CXCR2
      was strongly downregulated in neutrophils from diabetic mice compared with
      nondiabetic mice. Furthermore, CXCR2 downregulation was associated with increased
      G-protein-coupled receptor kinase 2 (GRK2) expression in these cells. Different
      from nondiabetic mice, diabetic animals submitted to mild sepsis displayed a
      significant augment in alpha1-acid glycoprotein (AGP) hepatic mRNA expression and
      serum protein levels. Administration of AGP in nondiabetic mice subjected to mild
      sepsis inhibited the neutrophil migration to the focus of infection, as well as
      induced l-selectin shedding and rise in CD11b of blood neutrophils. Insulin
      treatment of diabetic mice reduced mortality rate, prevented the failure of
      neutrophil migration, impaired GRK2-mediated CXCR2 downregulation, and decreased
      the generation of AGP. Finally, administration of AGP abolished the effect of
      insulin treatment in diabetic mice. Together, these data suggest that AGP may be
      involved in reduction of neutrophil migration and increased susceptibility to
      sepsis in diabetic mice.

PMID- 22415875
TI  - Calorie restriction reduces the influence of glucoregulatory dysfunction on
      regional brain volume in aged rhesus monkeys.
AB  - Insulin signaling dysregulation is related to neural atrophy in hippocampus and
      other areas affected by neurovascular and neurodegenerative disorders. It is not
      known if long-term calorie restriction (CR) can ameliorate this relationship
      through improved insulin signaling or if such an effect might influence task
      learning and performance. To model this hypothesis, magnetic resonance imaging
      was conducted on 27 CR and 17 control rhesus monkeys aged 19-31 years from a
      longitudinal study. Voxel-based regression analyses were used to associate
      insulin sensitivity with brain volume and microstructure cross-sectionally.
      Monkey motor assessment panel (mMAP) performance was used as a measure of task
      performance. CR improved glucoregulation parameters and related indices. Higher
      insulin sensitivity predicted more gray matter in parietal and frontal cortices
      across groups. An insulin sensitivity * dietary condition interaction indicated
      that CR animals had more gray matter in hippocampus and other areas per unit
      increase relative to controls, suggesting a beneficial effect. Finally, bilateral
      hippocampal volume adjusted by insulin sensitivity, but not volume itself, was
      significantly associated with mMAP learning and performance. These results
      suggest that CR improves glucose regulation and may positively influence specific
      brain regions and at least motor task performance. Additional studies are
      warranted to validate these relationships.

PMID- 22415876
TI  - Concordance of changes in metabolic pathways based on plasma metabolomics and
      skeletal muscle transcriptomics in type 1 diabetes.
AB  - Insulin regulates many cellular processes, but the full impact of insulin
      deficiency on cellular functions remains to be defined. Applying a mass
      spectrometry-based nontargeted metabolomics approach, we report here alterations
      of 330 plasma metabolites representing 33 metabolic pathways during an 8-h
      insulin deprivation in type 1 diabetic individuals. These pathways included those
      known to be affected by insulin such as glucose, amino acid and lipid metabolism,
      Krebs cycle, and immune responses and those hitherto unknown to be altered
      including prostaglandin, arachidonic acid, leukotrienes, neurotransmitters,
      nucleotides, and anti-inflammatory responses. A significant concordance of
      metabolome and skeletal muscle transcriptome-based pathways supports an
      assumption that plasma metabolites are chemical fingerprints of cellular events.
      Although insulin treatment normalized plasma glucose and many other metabolites,
      there were 71 metabolites and 24 pathways that differed between nondiabetes and
      insulin-treated type 1 diabetes. Confirmation of many known pathways altered by
      insulin using a single blood test offers confidence in the current approach.
      Future research needs to be focused on newly discovered pathways affected by
      insulin deficiency and systemic insulin treatment to determine whether they
      contribute to the high morbidity and mortality in T1D despite insulin treatment.

PMID- 22415878
TI  - Deletion of the androgen receptor in adipose tissue in male mice elevates retinol
      binding protein 4 and reveals independent effects on visceral fat mass and on
      glucose homeostasis.
AB  - Testosterone deficiency is epidemic in obese ageing males with type 2 diabetes,
      but the direction of causality remains unclear. Testosterone-deficient males and
      global androgen receptor (AR) knockout mice are insulin resistant with increased
      fat, but it is unclear whether AR signaling in adipose tissue mediates body fat
      redistribution and alters glucose homoeostasis. To investigate this, mice with
      selective knockdown of AR in adipocytes (fARKO) were generated. Male fARKO mice
      on normal diet had reduced perigonadal fat but were hyperinsulinemic and by age
      12 months, were insulin deficient in the absence of obesity. On high-fat diet,
      fARKO mice had impaired compensatory insulin secretion and hyperglycemia, with
      increased susceptibility to visceral obesity. Adipokine screening in fARKO mice
      revealed a selective increase in plasma and intra-adipose retinol binding protein
      4 (RBP4) that preceded obesity. AR activation in murine 3T3 adipocytes
      downregulated RBP4 mRNA. We conclude that AR signaling in adipocytes not only
      protects against high-fat diet-induced visceral obesity but also regulates
      insulin action and glucose homeostasis, independently of adiposity. Androgen
      deficiency in adipocytes in mice resembles human type 2 diabetes, with early
      insulin resistance and evolving insulin deficiency.

PMID- 22415877
TI  - No interactions between previously associated 2-hour glucose gene variants and
      physical activity or BMI on 2-hour glucose levels.
AB  - Gene-lifestyle interactions have been suggested to contribute to the development
      of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge
      are used to diagnose diabetes and are associated with both genetic and lifestyle
      factors. However, whether these factors interact to determine 2-h glucose levels
      is unknown. We meta-analyzed single nucleotide polymorphism (SNP) * BMI and SNP *
      physical activity (PA) interaction regression models for five SNPs previously
      associated with 2-h glucose levels from up to 22 studies comprising 54,884
      individuals without diabetes. PA levels were dichotomized, with individuals below
      the first quintile classified as inactive (20%) and the remainder as active
      (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h
      glucose levels than active individuals (beta = 0.22 mmol/L [95% CI 0.13-0.31], P
      = 1.63 * 10(-6)). All SNPs were associated with 2-h glucose (beta = 0.06-0.12
      mmol/allele, P <= 1.53 * 10(-7)), but no significant interactions were found with
      PA (P > 0.18) or BMI (P >= 0.04). In this large study of gene-lifestyle
      interaction, we observed no interactions between genetic and lifestyle factors,
      both of which were associated with 2-h glucose. It is perhaps unlikely that top
      loci from genome-wide association studies will exhibit strong subgroup-specific
      effects, and may not, therefore, make the best candidates for the study of
      interactions.

PMID- 22415879
TI  - Adiponectin increases skeletal muscle mitochondrial biogenesis by suppressing
      mitogen-activated protein kinase phosphatase-1.
AB  - Adiponectin enhances mitochondrial biogenesis and oxidative metabolism in
      skeletal muscle. This study aimed to investigate the underlying mechanisms
      through which adiponectin induces mitochondrial biogenesis in skeletal muscle.
      Mitochondrial contents, expression, and activation status of p38 mitogen
      activated protein kinase (MAPK) and PPARgamma coactivator 1alpha (PGC-1alpha)
      were compared between skeletal muscle samples from adiponectin gene knockout,
      adiponectin-reconstituted, and control mice. Adenovirus-mediated adiponectin and
      MAPK phosphatase-1 (MKP1) overexpression were used to verify the relationship of
      MKP1 and PGC-1alpha in adiponectin-enhanced mitochondrial biogenesis using
      cultured C2C12 myotubes and PGC-1alpha knockout mice. An inhibitory effect of
      adiponectin on MKP1 gene expression was observed in mouse skeletal muscle and
      cultured C2C12 myotubes. Overexpression of MKP1 attenuated adiponectin-enhanced
      mitochondrial biogenesis, with significantly decreased PGC-1alpha expression and
      p38 MAPK phosphorylation. Although in vivo adiponectin overexpression reduced
      MKP1 protein levels, the stimulative effects of adiponectin on mitochondrial
      biogenesis vanished in skeletal muscle of PGC-1alpha knockout mice. Therefore,
      our study indicates that adiponectin enhances p38 MAPK/PGC-1alpha signaling and
      mitochondrial biogenesis in skeletal muscle by suppressing MKP1 expression.

PMID- 22415880
TI  - The AGE-breaker ALT-711 restores high blood flow-dependent remodeling in
      mesenteric resistance arteries in a rat model of type 2 diabetes.
AB  - Flow-mediated remodeling of resistance arteries is essential for
      revascularization in ischemic diseases, but this is impaired in diabetes. We
      hypothesized that breaking advanced glycation end product (AGE) cross-links could
      improve remodeling in mesenteric resistance arteries in Zucker diabetic fatty
      (ZDF) rats compared with lean Zucker (LZ) rats. Arteries, exposed to high (HF) or
      normal (NF) blood flow after alternate arterial ligation in vivo, were collected
      after 2 weeks. In LZ rats, HF artery diameter was larger than for NF vessels, but
      this was not the case in ZDF rats. Endothelium-mediated dilation in ZDF rats,
      which was lower than in LZ rats, was further decreased in HF arteries. Treatment
      of rats with the AGE-breaker 4,5-dimethyl-3-phenacylthiazolium chloride (ALT-711)
      (3 mg/kg/day; 3 weeks) reversed diabetes-induced impairment of HF-dependent
      remodeling. ALT-711 also improved endothelium nitric oxide-dependent relaxation
      in mesenteric resistance arteries. Reactive oxygen species reduction restored
      relaxation in ZDF rats but not in LZ or ALT-711-treated rats. AGEs were reduced
      in ALT-711-treated ZDF rats compared with ZDF rats. Metalloproteinase activity,
      necessary for HF-dependent remodeling, was reduced in ZDF rats compared with LZ
      rats and restored by ALT-711. Thus, targeting AGE cross-links may provide a
      therapeutic potential for overcoming microvascular complications in ischemic
      disorders occurring in diabetes.

PMID- 22415881
TI  - The ATP-P2X7 signaling axis is dispensable for obesity-associated inflammasome
      activation in adipose tissue.
AB  - Inflammasome activation in adipose tissue has been implicated in obesity
      associated insulin resistance and type 2 diabetes. However, when and how
      inflammasome is activated in adipose tissue remains speculative. Here we test the
      hypothesis that extracellular ATP, a potent stimulus of inflammasome in
      macrophages via purinergic receptor P2X, ligand-gated ion channel, 7 (P2X(7)),
      may play a role in inflammasome activation in adipose tissue in obesity. Our data
      show that inflammasome is activated in adipose tissue upon 8-week feeding of 60%
      high-fat diet (HFD), coinciding with the onset of hyperglycemia and
      hyperinsulinemia as well as the induction of P2X(7) in adipose tissue.
      Unexpectedly, P2X(7)-deficient animals on HFD exhibit no changes in metabolic
      phenotypes, inflammatory responses, or inflammasome activation when compared with
      the wild-type controls. Similar observations have been obtained in hematopoietic
      cell-specific P2X(7)-deficient animals generated by bone marrow transplantation.
      Thus, we conclude that inflammasome activation in adipose tissue in obesity
      coincides with the onset of hyperglycemia and hyperinsulinemia but, unexpectedly,
      is not mediated by the ATP-P2X(7) signaling axis. The nature of the inflammasome
      activating danger signal(s) in adipose tissue in obesity remains to be
      characterized.

PMID- 22415883
TI  - A new supramolecular hole injection/transport material on conducting polymer for
      application in light-emitting diodes.
AB  - A new DNA-mimetic pi-conjugated polymer poly(triphenylamine-carbazole) (PTC-U)
      has been prepared which exhibits high thermal stability, non-corrosion, excellent
      hole injection and electron-blocking abilities in the solid state owing to the
      uracil induced physical cross-linking. In addition, a trilayer device with PTC-U
      as a hole injection/transport layer is approximately 1.6 times higher than that
      of the commercial product PEDOT:PSS-based devices.

PMID- 22415882
TI  - Species-specific biological effects of FGF-2 in articular cartilage: implication
      for distinct roles within the FGF receptor family.
AB  - Existing literature demonstrates that fibroblast growth factor-2 (FGF-2) exerts
      opposing, contradictory biological effects on cartilage homeostasis in different
      species. In human articular cartilage, FGF-2 plays a catabolic and anti-anabolic
      role in cartilage homeostasis, driving homeostasis toward degeneration and
      osteoarthritis (OA). In murine joints, however, FGF-2 has been identified as an
      anabolic mediator as ablation of the FGF-2 gene demonstrated increased
      susceptibility to OA. There have been no previous studies specifically addressing
      species-specific differences in FGF-2-mediated biological effects. In this study,
      we provide a mechanistic understanding by which FGF-2 exerts contradictory
      biological effects in human versus murine tissues. Using human articular
      cartilage (ex vivo) and a medial meniscal destabilization (DMM) animal model (in
      vivo), species-specific expression patterns of FGFR receptors (FGFRs) are
      elucidated between human and murine articular cartilage. In the murine OA model
      followed by intra-articular injection of FGF-2, we further correlate FGFR
      profiles to changes in behavioral pain perception, proteoglycan content in
      articular cartilage, and production of inflammatory (CD11b) and angiogenic (VEGF)
      mediators in synovium lining cells. Our results suggest that the fundamental
      differences in cellular responses between human and murine tissues may be
      secondary to distinctive expression patterns of FGFRs that eventually determine
      biological outcomes in the presence of FGF-2. The complex interplay of FGFRs and
      the downstream signaling cascades induced by FGF-2 in human cartilage should add
      caution to the use of this particular growth factor for biological therapy in the
      future.

PMID- 22415885
TI  - Nasopharyngeal necrosis after chronic opioid (oxycodone/acetaminophen)
      insufflation.
AB  - Nasopharyngeal necrosis resulting from narcotic insufflation is a recognized
      phenomenon, but cocaine use is more commonly associated with this pathology than
      opioid abuse. Physical exam findings associated with severe tissue destruction
      are not routinely seen on physical examination or available in the medical
      literature. We present a case of chronic oxycodone/acetaminophen insufflation and
      images of a defect in the soft palate.

PMID- 22415886
TI  - Unintentional chronic acetaminophen poisoning during pregnancy resulting in liver
      transplantation.
AB  - INTRODUCTION: Acetaminophen (APAP) is a widely used medication in pregnancy and
      is considered safe. Unfortunately, APAP is also among the most commonly reported
      agents implicated in overdoses during pregnancy. We present a unique case of a
      pregnant patient with fulminant hepatic failure resulting in a liver transplant
      from repeated supratherapeutic ingestions of APAP. CASE REPORT: A 22 year
      pregnant female presented with abdominal pain and hepatotoxicity after taking
      supratherapeutic amounts of APAP to treat dental pain. The patient denied
      intentional or acute ingestion of APAP but did admit to taking approximately 8-9
      grams of APAP per day for 10-14 days for dental pain. Other cause of
      hepatotoxicity, including acute fatty liver of pregnancy, were evaluated for and
      ruled out. She developed fulminant hepatic failure and required liver
      transplantation which was successful. The pregnancy remained viable through the
      operation but intrauterine fetal demise occurred 2 weeks later. An MRI of the
      fetus showed extensive peri-cerebral and intraventricular hemorrhage with
      extensive periventricular leukomalacia. DISCUSSION: The degree of morbidity from
      repeated supratherapeutic ingestions of APAP seen in this case is rare and poorly
      described in a pregnant patient. There are no prior reports describing the need
      for liver transplant after repeated supratherapeutic ingestions of APAP during
      pregnancy. Along with the typical cause of hepatotoxicy several unique pregnancy
      related causes also had to be evaluated for. This case highlights the significant
      morbidity that can occur with even unintentional APAP toxicity and the need to
      educate patients, especially pregnant patients, of the risk of excessive APAP
      use.

PMID- 22415887
TI  - Helicobacter pylori induces promoter methylation of E-cadherin via interleukin
      1beta activation of nitric oxide production in gastric cancer cells.
AB  - BACKGROUND: Helicobacter pylori infection causes gastric mucosal inflammatory
      responses, resulting in up-regulation of interleukin-1beta (IL-1beta) and
      overproduction of mutagenic nitric oxide (NO). The authors previously
      demonstrated that IL-1beta plays an important role in H. pylori-induced E
      cadherin (E-cad) methylation. Here, they extend the study to investigate the
      downstream effect of IL-1beta on H. pylori-induced gastric inflammation and
      aberrant DNA methylation. METHODS: Human gastric cancer cell lines (MKN7, MKN74,
      and TMK-1) with and without pretreatment of IL-1 receptor antagonist (IL-1ra)
      were treated with IL-1beta or infected with H. pylori. Promoter methylation
      status of E-cad was examined by methylation-specific polymerase chain reaction
      (PCR). Expression of E-cad, inducible nitric oxide synthase (iNOS), and nuclear
      factor kappaB (NFkappaB) was assessed by quantitative reverse transcriptase PCR,
      Western blotting, or immunofluorescence. NO production and total DNA
      methyltransferase (DNMT) activity were assayed fluorometrically. RESULTS: Both IL
      1beta treatment and H. pylori infection-induced E-cad methylation led to a
      decrease in E-cad expression at both mRNA and protein levels. Total DNMT
      enzymatic activity was significantly elevated in treated cells, accounting for
      the observed E-cad methylation induction. Increased expression of NFkappaB was
      accompanied by up-regulation of iNOS and production of NO in treated cells.
      Reversal of all these phenomena in cells pretreated with IL-1ra suggested H.
      pylori-induced E-cad methylation via IL-1beta stimulation of the NFkappaB
      transcriptional system, leading to activation of DNMT activity by NO production.
      CONCLUSIONS: These findings reveal a previously unknown effect of IL-1beta and NO
      on H. pylori-induced aberrant DNA methylation. This possible pathway indicates
      the role of NO in epigenetic modification that links inflammation to
      carcinogenesis.

PMID- 22415888
TI  - Influence of diabetes on efficacy of aliskiren, losartan or both on left
      ventricular mass regression.
AB  - HYPOTHESIS/ INTRODUCTION: We investigated whether diabetes modified the
      effectiveness of renin-angiotensin-aldosterone system (RAAS) inhibition on left
      ventricular hypertrophy (LVH) regression in hypertensive patients in the
      Aliskiren in Left Ventricular Hypertrophy (ALLAY) trial. MATERIALS AND METHODS:
      Participants (n=465) with LVH and a BMI > 25 kg/m(2) were randomized to aliskiren
      300mg, losartan 100mg or both daily for 36 weeks, and LVH regression was assessed
      by cardiac magnetic resonance imaging. Renin concentration, plasma renin activity
      and aldosterone were assessed in a subset of patients. RESULTS: Patients with
      diabetes mellitus (DM) (n=111, 24%) were older (61+/-9 vs. 58+/-11 years,
      p=0.03), had higher BMI (32.2+/-4.2 vs. 30.7 +/- 4 kg/m(2), p=0.004), higher
      systolic blood pressure (148+/-14 vs. 145+/-14mmHg, p=0.03) and lower eGFR (79+/
      16 vs. 84+/-16ml/min, p=0.03) at baseline. Combination therapy with aliskiren
      plus losartan was associated with greater LVH reduction than losartan alone in
      patients with DM (p=0.01), but not in patients without DM (p=0.91; unadjusted
      interaction p=0.06; adjusted p = 0.038). In a subset of 138 participants, plasma
      aldosterone was reduced to a greater extent in patients with DM (p-interaction =
      0.004). CONCLUSIONS: Patients with DM and LVH may derive differential benefit
      with dual RAAS inhibition with a combination of aliskiren and losartan compared
      with losartan alone with respect to LVH reduction. Whether these findings will
      result in improved outcomes will be further explored in larger studies.

PMID- 22415889
TI  - Total syntheses of the elusive welwitindolinones with bicyclo[4.3.1] cores.
AB  - The welwitindolinones with bicyclo[4.3.1] cores are a class of natural products
      that have attracted tremendous interest from the synthetic community because of
      their fascinating structures and promising biological profiles. More than 15
      research groups worldwide have reported progress toward these elusive natural
      products. This Minireview describes contemporary studies aimed at the total
      synthesis of these challenging targets, in addition to the two recently completed
      syntheses of welwitindolinones with bicyclo[4.3.1] cores reported by Rawal and
      Garg in 2011. Both of the completed efforts rely on C4-C11 bond constructions to
      access the congested bicyclic framework of these elusive natural products.

PMID- 22415890
TI  - Should we screen for and treat lower urinary tract dysfunction after major pelvic
      surgery? ICI-RS 2011.
AB  - AIMS: Given the relative frequency of lower urinary tract dysfunction (LUTD)
      after major pelvic surgery, the main question for this debate is: "Should we
      [actively] screen for LUTD after major pelvic surgery," with the intention to
      treat and improve patient care. METHODS: The discussants selected relevant papers
      from a limited review of the literature [PubMed/Medline database (January 1966 to
      May 2011)] and prepared the YES versus NO presentations. RESULTS: The evidence
      was presented for the following major pelvic procedures: colorectal surgery,
      hysterectomy, and surgery for other benign gynecologic conditions, radical
      prostatectomy, brachytherapy, and primary cryotherapy for prostate cancer. Based
      on the presentations, the audience voted in favor of screening for LUTD after
      major pelvic surgery. CONCLUSIONS: Irreversible treatment should be delayed in
      case of LUTD after major pelvic surgery. In fact, most symptoms spontaneously
      subside within 6 months after the surgery. Once the period of 6-12 months of
      conservative management has been completed and if LUTD persists, a new urodynamic
      screening should be followed by appropriate treatment.

PMID- 22415891
TI  - Total variation versus wavelet-based methods for image denoising in fluorescence
      lifetime imaging microscopy.
AB  - We report the first application of wavelet-based denoising (noise removal)
      methods to time-domain box-car fluorescence lifetime imaging microscopy (FLIM)
      images and compare the results to novel total variation (TV) denoising methods.
      Methods were tested first on artificial images and then applied to low-light live
      cell images. Relative to undenoised images, TV methods could improve lifetime
      precision up to 10-fold in artificial images, while preserving the overall
      accuracy of lifetime and amplitude values of a single-exponential decay model and
      improving local lifetime fitting in live-cell images. Wavelet-based methods were
      at least 4-fold faster than TV methods, but could introduce significant
      inaccuracies in recovered lifetime values. The denoising methods discussed can
      potentially enhance a variety of FLIM applications, including live-cell, in vivo
      animal, or endoscopic imaging studies, especially under challenging imaging
      conditions such as low-light or fast video-rate imaging.

PMID- 22415893
TI  - On oxygen-containing groups in chemically modified graphenes.
AB  - Reduced graphenes (belonging to the class of chemically modified graphenes, CMG)
      are one of the most investigated and utilized materials in current research.
      Oxygen functionalities on the CMG surfaces have dramatic influences on material
      properties. Interestingly, these functionalities are rarely comprehensively
      characterized. Herein, the four most commonly used CMGs, mainly electrochemically
      reduced graphene oxide (ER-GO), thermally reduced graphene oxide (TR-GO), and the
      corresponding starting materials, that is, graphene oxide and graphite oxide,
      were comprehensively characterized by a wide variety of methods, such as high
      resolution X-ray photoelectron spectroscopy, electrochemical impedance
      spectroscopy, UV/Vis spectroscopy, transmission electron microscopy (TEM), and
      voltammetry, to establish connections between the structures of these materials
      that carry different oxygen functionalities and their electrochemical behaviors.
      This was followed by the quantification of the negatively charged oxygen
      containing groups (OCGs) by UV/Vis spectroscopy and of the electrochemically
      reducible OCGs by voltammetry. Lastly, a biofunctionalization with gold
      nanoparticle (AuNP)-modified DNA sequences was performed by the formation of
      covalent bonds with the carboxylic groups (-COOH) on the CMG surfaces. There was
      an evident predominance of functionalizable -COOH groups on the ER-GO surface, as
      confirmed by a higher amount of Au detected both with differential-pulse
      voltammetry and impedance spectroscopy, coupled with visualization by TEM. We
      exploited the DNA-Au bioconjugates as highly specific stains to localize and
      visualize the positions of carboxylic groups. Our findings are very important to
      clearly identify the presence, nature, and distribution of oxygen functionalities
      on different chemically modified graphenes.

PMID- 22415892
TI  - Integration of global resources for human genetic variation and disease.
AB  - There is an increasing accumulation of data on disease-related mutations and
      associated phenotypes in a wide variety of databases worldwide. Exploiting these
      data in the context of whole genome sequencing is inhibited because the phenotype
      information in these databases is often difficult to search meaningfully or
      relate between data sets, and automated computational integration is not
      possible. Key to this integration is the development of ontology-based methods
      for describing diseases in terms of their component phenotypes. This would allow
      analysis of variation in disease manifestation, relationships between diseases
      and phenotypes in model organisms, and linking diseases to gene mutations,
      pathways, and phenotypes. Building a systematic link to phenotypes manifested in
      model organisms will be of particular importance with the advent of new, large
      scale phenotyping projects such as the International Mouse Phenotyping
      Consortium. In addition to improved semantic description, funding and
      organizational innovations are required to support this integration. In
      particular, a series of national or international hubs to hold genotype and
      phenotype data are needed which could feed data to a central database. In
      addition, better coordination of clinical and bioinformatics experts and,
      crucially, development of a transnational funding and international coordination
      infrastructure will be required.

PMID- 22415894
TI  - Simultaneous determination of atorvastatin and niacin in human plasma by LC-MS/MS
      and its application to a human pharmacokinetic study.
AB  - A rapid, simple, sensitive and selective LC-MS/MS method has been developed and
      validated for quantification of the atorvastatin (AT) and niacin (NA) in 250 MUL
      human plasma. The analytical procedure involves a liquid-liquid extraction method
      using nevirapine as an internal standard (IS). The chromatographic separation was
      achieved on a Hypurity Advance (4.6 * 50 mm, 5 um) column using a mobile phase
      consisting of 0.1% formic acid buffer-acetonitrile (20:80, v/v) at flow rate of
      0.8 mL/min. The API-4000 LC-MS/MS was operated in the multiple-reaction
      monitoring mode using electrospray ionization. The total run time of analysis was
      3 min and elution of AT, NA and IS occurred at 1.06, 1.84 and 0.92 min,
      respectively. A detailed validation of the method was performed as per the US
      Food and Drug Administration guidelines and the standard curves found to be
      linear in the range of 0.10-30.0 ng/mL for AT and 20.2-6026 ng/mL for NA, with a
      coefficient of correlation of >= 0.99 for both the compounds. AT and NA were
      found to be stable in a battery of stability studies, viz. bench-top,
      autosampler, re-injection, wet-extract and repeated freeze-thaw cycles. The
      developed assay method was successfully applied to a pharmacokinetic study in
      humans.

PMID- 22415895
TI  - Facile fabrication of light, flexible and multifunctional graphene fibers.
AB  - Macroscopic graphene fibers with strength comparable to carbon nanotube yarns
      have been fabricated with a facile dimensionally-confined hydrothermal strategy
      from low-cost, aqueous graphite oxide suspensions, which is shapable, weavable,
      and has a density of less than 1/7 conventional carbon fibers. In combination
      with the easy in situ and post-synthesis functionalization, the highly flexible
      graphene fibers can be woven into smart textiles.

PMID- 22415896
TI  - An aqueous orally active vaccine targeted against a RAGE/AB complex as a novel
      therapeutic for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that
      gradually destroys a person's memory. Substantial evidence suggests that amyloid
      beta (Abeta) and the receptor for advanced glycation endproducts (RAGE) play an
      important and often deleterious role in the pathogenesis of AD. RAGE facilitates
      the translocation of Abeta from the periphery into the brain, mediates the Abeta
      induced neurotoxicity, and enhances the release of pro-inflammatory cytokines
      increasing the inflammatory response. In addition, soluble forms of RAGE (sRAGE)
      and Abeta bind together in the periphery forming high molecular weight complexes
      that are more highly immunogenic and less neurotoxic than Abeta1-42 alone. We
      show here that there are elevated anti-RAGE and anti-Abeta titers (in a near 1:1
      relationship) in samples analyzed from human AD patients, aged non-human
      primates, and AD transgenic mice (APPSWE-PS1). We show that an in vitro prepared
      RAGE/Abeta complex induces a greater immunogenic response (increased anti-Abeta1
      42 and anti-RAGE antibody titers) in both human peripheral blood mononuclear
      cells (PBMCs) and immunized Balb-C mice than does either Abeta1-42 or RAGE alone.
      Further, pretreatment with endogenous anti-RAGE antibodies isolated from our
      transgenic APPSWE-PS1 mice can prevent Abeta1-42-induced neurotoxicity in
      cultured primary rat cortical neurons. Finally, we examine the effectiveness of
      an orally administered vaccine of either RAGE/Abeta complex or Abeta1-42 alone in
      improving cognitive function in our AD transgenic mice. Our results to date
      support the hypothesis that a protein complex vaccine that targets both RAGE and
      Abeta1-42 will provide a more effective treatment for AD than vaccination with
      Abeta1-42 alone.

PMID- 22415897
TI  - Pure and mixed fibrolamellar hepatocellular carcinomas differ in natural history
      and prognosis after complete surgical resection.
AB  - BACKGROUND: The purpose of the current study was to describe pure and mixed
      fibrolamellar hepatocellular carcinoma (FL-HCC). METHODS: Consecutive patients
      with pure and mixed FL-HCC were identified from a central pathological review
      using Edmondson's criteria. Clinical, pathological, and epigenetic
      characteristics of patients who underwent curative surgery were evaluated.
      Overall and disease-free survival as well as patterns of disease recurrence were
      examined. Methylation levels of L1 retrotransposon (LINE-1) repetitive elements
      and Ras association domain family 1A gene (RASSF1) promoter were also assessed
      using pyrosequencing. RESULTS: Forty of 53 patients with a median age of 22 years
      (range, 9 years-;65 years) met the criteria for analysis. Central pathological
      review found that 30 patients (75%) had pure and 10 patients (25%) had mixed FL
      HCC. Pure FL-HCC typically occurred in patients aged < 30 years. These patients
      often presented with lymph node metastasis at the time of diagnosis and
      frequently experienced extrahepatic recurrences (n = 16). Conversely, mixed FL
      HCC appeared to resemble to classic HCC, occurring in patients aged > 40 years
      and frequently involving the liver as the primary site of disease recurrence.
      With a median follow-up of 7.8 years, the median overall survival from the time
      of diagnosis in all patients was 6.4 years (range, 3.2 years-12 years).
      Multivariate analysis found that the risk of death was increased in patients with
      higher American Joint Committee on Cancer disease stages (P = .003) and those
      with mixed FL-HCC (P = .03). Methylation analysis of LINE-1 repetitive elements
      and RASSF1 promoter revealed different methylation levels between pure and mixed
      FL-HCC, suggesting a different epigenetic background. CONCLUSIONS: Pure and mixed
      FL-HCC display distinct clinical presentations and epigenetic backgrounds leading
      to different prognoses and as such may be regarded as separate clinical entities.

PMID- 22415898
TI  - Using factor mixture analysis to model heterogeneity, cognitive structure, and
      determinants of dementia: an application to the Aging, Demographics, and Memory
      Study.
AB  - The Aging, Demographics, and Memory Study is the first extensive study of
      cognitive impairment and dementia of population in the USA. A large sample of
      participants with ages 71 years or older has answered an in-depth questionnaire
      which included an extensive cognitive assessment. One of the principal aims of
      the study was to assign a diagnosis of dementia, cognitive impairment but not
      demented, or normal to the respondents. Because of this heterogeneity, we apply
      factor mixture model to the set of neuropsychological measures of the study in
      order to perform clustering of subjects and dimension reduction simultaneously.
      Moreover, we consider an extended variant of the model by incorporating a set of
      demographics and clinical covariates which directly affect the latent variables
      of the factor mixture model. The interest of the analysis is to investigate
      whether respondents exhibit the same association of overall cognitive functioning
      with the covariates or whether groups of respondents exist that exhibit different
      association with the covariates, indicating different determinants of overall
      cognitive functioning.

PMID- 22415899
TI  - An automated approach for segmentation of intravascular ultrasound images based
      on parametric active contour models.
AB  - This paper presents a fully automated approach to detect the intima and media
      adventitia borders in intravascular ultrasound images based on parametric active
      contour models. To detect the intima border, we compute a new image feature
      applying a combination of short-term autocorrelations calculated for the contour
      pixels. These feature values are employed to define an energy function of the
      active contour called normalized cumulative short-term autocorrelation.
      Exploiting this energy function, the intima border is separated accurately from
      the blood region contaminated by high speckle noise. To extract media-adventitia
      boundary, we define a new form of energy function based on edge, texture and
      spring forces for the active contour. Utilizing this active contour, the media
      adventitia border is identified correctly even in presence of branch openings and
      calcifications. Experimental results indicate accuracy of the proposed methods.
      In addition, statistical analysis demonstrates high conformity between manual
      tracing and the results obtained by the proposed approaches.

PMID- 22415900
TI  - A chiral bis(betaine) catalyst for the Mannich reaction of azlactones and
      aliphatic imines.

PMID- 22415901
TI  - Evaluation of five risk prediction models for elective abdominal aortic aneurysm
      repair using the UK National Vascular Database.
AB  - BACKGROUND: There is no consensus on the best risk prediction model for mortality
      following elective abdominal aortic aneurysm (AAA) repair. The objective was to
      evaluate the performance of five risk prediction models using the UK National
      Vascular Database (NVD). METHODS: Data on elective AAA repairs from the NVD
      between January 2008 and December 2010 were analysed. The models assessed were:
      Glasgow Aneurysm Score (GAS), Vascular Biochemical and Haematological Outcome
      Model (VBHOM), physiological component of the Vascular Physiological and
      Operative Severity Score for enUmeration of Mortality (V-POSSUM), Medicare and
      Vascular Governance North West (VGNW). Overall model discrimination and
      calibration in equally sized risk-group quintiles were assessed. RESULTS: The
      study cohort included 10,891 patients undergoing elective AAA repair (median age
      74 years, 87.3 per cent men). The in-hospital mortality rates following
      endovascular and open repair were 1.3 and 4.7 per cent respectively (2.9 per cent
      overall). The Medicare and VGNW models both showed good discrimination (area
      under receiver operating characteristic (ROC) curve 0.71), whereas the GAS, VBHOM
      and V-POSSUM models showed poor discrimination (area under ROC curve 0.60, 0.61
      and 0.62 respectively). The VGNW model was the only one to predict the overall
      mortality rate in the cohort (3.3 per cent predicted versus 2.9 per cent
      observed; P = 0.066). The VGNW model demonstrated good calibration, predicting
      risk accurately in four risk-group quintiles. The Medicare, V-POSSUM and VBHOM
      models accurately predicted risk in three, two and no risk-group quintiles
      respectively. CONCLUSION: The Medicare and VGNW models contain similar risk
      factors and showed good discrimination when applied to the NVD. Both models would
      be suitable for risk prediction after elective AAA repair in the UK.

PMID- 22415902
TI  - A green chemistry of graphene: photochemical reduction towards monolayer graphene
      sheets and the role of water adlayers.
AB  - Clean sheets: Stable aqueous dispersions of graphene sheets (GSs) are obtained by
      exposing graphene oxide to irradiation with light at room temperature, without
      using any chemical additives. The photochemical reduction method is sustainable
      and scalable, repairs a majority of defects in the graphene layers, and can be
      used to fine-tune surface functional groups. Interestingly, the aqueous GS
      dispersions are stable without any added surfactant. The existence of a water
      layer that is strongly bound to GS is evidenced.

PMID- 22415903
TI  - Strategies for tissue and organ decellularization.
AB  - Decellularized tissues have been successfully used in a variety of tissue
      engineering/regenerative medicine applications, and more recently decellularized
      organs have been utilized in the first stages of organ engineering. The protocols
      used to decellularize simple tissues versus intact organs differ greatly. Herein,
      the most commonly used decellularization methods for both surgical mesh materials
      and whole organs are described, with consideration given to how these different
      processes affect the extracellular matrix and the host response to the scaffold.

PMID- 22415904
TI  - Concise review: Adipose-derived stem cells as a novel tool for future
      regenerative medicine.
AB  - The potential use of stem cell-based therapies for the repair and regeneration of
      various tissues and organs offers a paradigm shift that may provide alternative
      therapeutic solutions for a number of diseases. The use of either embryonic stem
      cells (ESCs) or induced pluripotent stem cells in clinical situations is limited
      due to cell regulations and to technical and ethical considerations involved in
      the genetic manipulation of human ESCs, even though these cells are,
      theoretically, highly beneficial. Mesenchymal stem cells seem to be an ideal
      population of stem cells for practical regenerative medicine, because they are
      not subjected to the same restrictions. In particular, large number of adipose
      derived stem cells (ASCs) can be easily harvested from adipose tissue.
      Furthermore, recent basic research and preclinical studies have revealed that the
      use of ASCs in regenerative medicine is not limited to mesodermal tissue but
      extends to both ectodermal and endodermal tissues and organs, although ASCs
      originate from mesodermal lineages. Based on this background knowledge, the
      primary purpose of this concise review is to summarize and describe the
      underlying biology of ASCs and their proliferation and differentiation
      capacities, together with current preclinical and clinical data from a variety of
      medical fields regarding the use of ASCs in regenerative medicine. In addition,
      future directions for ASCs in terms of cell-based therapies and regenerative
      medicine are discussed.

PMID- 22415905
TI  - Determination of gemifloxacin on dried blood spots by hydrophilic interaction
      liquid chromatography with fluorescence detector: application to pharmacokinetics
      in rats.
AB  - A highly selective, sensitive and rapid hydrophilic liquid interaction
      chromatographic method was developed and validated for determination of
      gemifloxacin on dried blood spots. The chromatographic separation was achieved on
      a reversed-phase zwitterionic hydrophilic interaction liquid chromatographic
      ZIC(r)HILIC-C18 (4.6 * 100 mm; 5 um) column using acetonitrile-10 mM ammonium
      acetate (pH 3.5; 80:20, v/v) as a mobile phase in an isocratic elution mode at a
      flow rate 0.6 mL/min at 27  degrees C. An on-line fluorescence detector set at
      excitation and emission wavelengths of 269 and 393 nm, respectively was used for
      monitoring column eluents. Ciprofloxacin was used as an internal standard. The
      method was validated for accuracy, precision, linearity and selectivity by design
      of experiments following ICH guidelines. The assay exhibited a linear range of 25
      5000 ng/mL for gemifloxacin on dried blood spots. The lower limit of detection
      was found to be 10 ng/mL. The intra- and inter-assay coefficients of variation
      did not exceed 7.4% deviation of the nominal concentration. The recovery of GFX
      from dried blood spots was >95.0% and its stability was excellent with no
      evidence of degradation during sample processing for at least 3 months storage in
      a freezer at -20  degrees C.

PMID- 22415906
TI  - Carotid jugular arteriovenous fistula: an unusual complication of internal
      jugular vein catheterization in children.
AB  - Central venous catheterization is essential in the management of patients
      requiring long-term intravenous access. Various risks during central line
      insertion have been described in the medical literature, including the
      potentially life-threatening complication of iatrogenic arteriovenous fistula
      (AVF). We describe a novel case of carotid jugular AVF following implanted port
      (BardPort(r) by C.R. Bard, Inc.) insertion in a pediatric oncology patient who
      had suffered cerebral infarct due to thromboembolism. Pediatr Blood Cancer 2012;
      59: 1302-1304. (c) 2012 Wiley Periodicals, Inc.

PMID- 22415907
TI  - Nocturia Think Tank: focus on nocturnal polyuria: ICI-RS 2011.
AB  - The following is a report of the proceedings of the Nocturia Think Tank sessions
      of the annual International Consultation on Incontinence-Research Society, which
      took place June 13-15, 2011 in Bristol, UK. The report is organized into sections
      pertaining to the main topics of discussions having occurred at that meeting,
      centering on the relationship of nocturnal polyuria (NP) and nocturia but also
      synthesizing more current evidence advancing our knowledge of the diagnosis and
      management of nocturia. This article is not meant to be a comprehensive review on
      the subject of nocturia, a number of which are available in the recent
      literature. All authors were physically present during, or in a preliminary
      session just prior to, the meeting in Bristol.

PMID- 22415908
TI  - Organotin-catalyzed highly regioselective thiocarbonylation of nonprotected
      carbohydrates and synthesis of deoxy carbohydrates in a minimum number of steps.
AB  - Nonprotected carbohydrates: The catalytic regioselective thiocarbonylation of
      carbohydrates by using organotin dichloride under mild conditions was
      demonstrated. The reaction afforded various deoxy saccharides in high yields and
      excellent regioselectivity in a minimum number of steps. The regioselectivity of
      the thiocarbonylation is attributed to the intrinsic character of the
      carbohydrates based on the stereorelationship of their hydroxy groups (see
      scheme).

PMID- 22415909
TI  - Bioinspired layered composites based on flattened double-walled carbon nanotubes.
AB  - Inspired by the layered hierarchical nano- and microstructures of natural nacre,
      flattened double-walled carbon nanotube (FDWCNT) reinforced epoxy composites are
      fabricated. Impressively, the prepared composites exhibit layered structures
      analogous to nacre, and the FDWCNT loading can reach 70 wt%, which results in
      superior mechanical properties that evidently outperform other existing
      materials.

PMID- 22415910
TI  - A new permutation-based method for assessing agreement between two observers
      making replicated quantitative readings.
AB  - The coefficient of individual equivalence is a permutation-based measure of
      agreement between two observers making replicated readings on each subject. It
      compares the observed disagreement between the observers to the expected
      disagreement under individual equivalence. Individual equivalence of observers
      requires that for every study subject, the conditional distributions of the
      readings of the observers given the subject's characteristics are identical.
      Therefore, under individual equivalence it does not matter which observer is
      making a particular reading on a given subject. We introduce both nonparametric
      and parametric methods to estimate the coefficient as well as its standard error.
      We compare the new coefficient with the coefficient of individual agreement and
      with the concordance correlation coefficient. We also evaluate the performance of
      the estimates of the new coefficient via simulations and illustrate this new
      approach using data from a study comparing two noninvasive techniques for
      measuring carotid stenosis to an invasive gold standard.

PMID- 22415912
TI  - Amblyopia: background to the special issue on stroke recovery.
AB  - In this introductory article, we summarize the evidence from humans and animal
      models on the shaping of postnatal visual development by focused binocular input.
      When balanced input is missing during a sensitive period, deficits emerge,
      including seemingly permanent impairments in visual acuity that are labeled
      amblyopia. Rodent models have identified neurochemical changes that control the
      onset of such sensitive periods and molecular and structural brakes that lead to
      the diminution of the plasticity thereafter. Both animal and human studies of
      amblyopia have recently identified exciting ways to remediate vision in adulthood
      that bear some similarity to the interventions that have proved successful in
      promoting recovery from stroke.

PMID- 22415913
TI  - Functional connectivity and neurological recovery.
AB  - Modern theories of brain function emphasize the importance of distributed
      functional networks and synchronized activity within and between networks in
      mediating cognitive functions. This view highlights the importance of considering
      brain-behavior relationships after focsal lesions not only as the result of local
      structural damage but also as a more widespread alteration of the physiological
      state of networks connected to the lesion. Recent findings demonstrate coherent
      activity in large-scale brain networks not only during task performance, but
      also, surprisingly, at rest in the absence of stimuli, tasks, or overt responses.
      Moreover, breakdown of coherent activity at rest, even in regions that are
      structurally intact, correlates with behavioral deficits and with their recovery
      after injury. This network perspective is fundamental to understand not only
      healthy brain function, but also the pathophysiology of brain injuries,
      mechanisms of functional recovery, and the basis for novel interventions for
      therapy.

PMID- 22415915
TI  - From motor cortex to visual cortex: the application of noninvasive brain
      stimulation to amblyopia.
AB  - Noninvasive brain stimulation is a technique for inducing changes in the
      excitability of discrete neural populations in the human brain. A current model
      of the underlying pathological processes contributing to the loss of motor
      function after stroke has motivated a number of research groups to investigate
      the potential therapeutic application of brain stimulation to stroke
      rehabilitation. The loss of motor function is modeled as resulting from a
      combination of reduced excitability in the lesioned motor cortex and an increased
      inhibitory drive from the nonlesioned hemisphere over the lesioned hemisphere.
      This combination of impaired neural function and pathological suppression
      resonates with current views on the cause of the visual impairment in amblyopia.
      Here, we discuss how the rationale for using noninvasive brain stimulation in
      stroke rehabilitation can be applied to amblyopia, review a proof-of-principle
      study demonstrating that brain stimulation can temporarily improve amblyopic eye
      function, and propose future research avenues.

PMID- 22415914
TI  - Recovery of motor function after stroke.
AB  - The human brain possesses a remarkable ability to adapt in response to changing
      anatomical (e.g., aging) or environmental modifications. This form of
      neuroplasticity is important at all stages of life but is critical in
      neurological disorders such as amblyopia and stroke. This review focuses upon our
      new understanding of possible mechanisms underlying functional deficits evidenced
      after adult-onset stroke. We review the functional interactions between different
      brain regions that may contribute to motor disability after stroke and, based on
      this information, possible interventional approaches to motor stroke disability.
      New information now points to the involvement of non-primary motor areas and
      their interaction with the primary motor cortex as areas of interest. The
      emergence of this new information is likely to impact new efforts to develop more
      effective neurorehabilitative interventions using transcranial magnetic
      stimulation (TMS) and transcranial direct current stimulation (tDCS) that may be
      relevant to other neurological disorders such as amblyopia.

PMID- 22415916
TI  - Parallels between use of constraint-induced movement therapy to treat
      neurological motor disorders and amblyopia training.
AB  - There are striking similarities between the visual defect of amblyopia and the
      motor deficit of the extremities produced by such types of damage to the central
      nervous system (CNS) as stroke and traumatic brain injury, both after and before
      maturity. Part of the motor deficit of the extremities following CNS injury can
      be attributed to a learning phenomenon termed "learned nonuse" or if present from
      birth, "developmental disregard." The same mechanism is hypothesized to be
      involved in the development of amblyopia. Treatments that are efficacious in the
      remediation of these defects, Constraint-Induced Movement therapy and amblyopia
      training, also share a number of strong similarities. In addition, plastic brain
      changes are produced by CI therapy and are hypothesized to occur during amblyopia
      training.

PMID- 22415917
TI  - The mirror neuron system and treatment of stroke.
AB  - Mirror neurons discharge during the execution of ecological goal-directed manual
      and oral actions, as well as during the observation of the same actions done by
      other individuals. These neurons were first identified in the ventral premotor
      cortex (PMv; area F5) and later on in the inferior parietal lobule (areas PF and
      PFG) of monkey brain, constituting a "mirror neuron" system. Several pieces of
      experimental data suggest that a mirror neuron system devoted to hand, mouth, and
      foot actions might also be present in humans. In the present paper, we review the
      experimental evidence on the role of the mirror neuron system in action
      understanding and imitation, both in hand motor function and speech. Based on the
      features of the mirror neuron system and its role in action understanding and
      imitation, we discuss the use of action observation and imitation as an approach
      for systematic training in the rehabilitation of patients with motor impairment
      of the upper limb and aphasia following stroke. We present the results of some
      preliminary studies to test this concept, and a discussion of network models as a
      measure of neurobiological change.

PMID- 22415918
TI  - Age, experience, injury, and the changing brain.
AB  - The fundamental concept in the emerging field of rehabilitation and brain
      plasticity is that although there is much constancy in brain function and
      organization across our lifetime, there is remarkable variability as well. This
      variability reflects the brain's capacity to alter its structure and function in
      reaction to environmental diversity as well as to perturbations including injury
      throughout the lifespan. Although the term brain plasticity is now widely used,
      it is not easily defined and is used to refer to changes at many levels in the
      nervous system ranging from molecular events, such as changes in gene expression,
      to behavior (e.g., Shaw & McEachern (Eds.) [2001]. Toward a Theory of
      Neuroplasticity. Philadelphia, USA: Psychology Press). The focus of our work has
      been to correlate changes in behavior, neuronal morphology, and the organization
      of motor maps after cortical injury throughout the lifespan. In this article, we
      review evidence we have collected from a rat model of normal development and the
      effects of brain injury, and comment on the general principals that may apply to
      human stroke and amblyopia.

PMID- 22415919
TI  - Stroke recovery and sensory plasticity: common mechanisms?
AB  - Presentations in this symposium are considered in the context of mechanisms of
      sensory plasticity, particularly in the auditory system. The auditory nervous
      system has two discrete end organs that are separately vulnerable to clinical and
      experimental injury, and brainstem processing mechanisms that are highly
      specialized for temporal, spectral, and spatial coding. These include giant axo
      somatic synapses and neurons with spatially segregated bipolar dendrites, each
      innervated exclusively from one ear. This architecture allows exquisite control
      of afferent-target interactions, including known excitatory and inhibitory
      couplings, and consequently enhanced interpretation of data from other brain
      systems. For example, deafening can silence the auditory nerve, but has
      surprisingly little impact on normal brain function, as evidenced by the success
      of cochlear implants. The observed amplification from one brain region to another
      of degeneration following stroke or discrete brain lesions may thus be due to
      secondary rather than primary afferent consequences of the lesion.

PMID- 22415920
TI  - Sensitive periods for language and recovery from stroke: conceptual and practical
      parallels.
AB  - In this review, we consider the literature on sensitive periods for language
      acquisition from the perspective of the stroke recovery literature treated in
      this Special Issue. Conceptually, the two areas of study are linked in a number
      of ways. For example, the fact that learning itself can set the stage for future
      failures to learn (in second language learning) or to remediate (as described in
      constraint therapy) is an important insight in both areas, as is the increasing
      awareness that limits on learning can be overcome by creating the appropriate
      environmental context. Similar practical issues, such as distinguishing native
      like language acquisition or recovery of function from compensatory mechanisms,
      arise in both areas as well.

PMID- 22415921
TI  - The effects of injury to dynamic neural networks in the mature and developing
      brain.
AB  - This special section emphasizes three key factors relevant to understanding brain
      responses to injury. First, it is important to consider the impact of injury on
      brain networks rather then just the localized neuropathology. In contrast to
      older localizationist models, neural systems views emphasize that the effects of
      localized injury cascade through the neural system altering function at multiple
      levels. Thus, effective remediation must accommodate the multiple effects of
      brain injury. Second, the role of neural plasticity in the brain response to
      injury is critical. Rehabilitation implies that neural system is adaptive and
      capable of changing in response to input. Thus exploiting the brain's inherent
      plasticity is central to remediation. Finally, the timing of injury is an
      essential consideration. Adult injury disrupts stable neural systems and
      plasticity operates to regain functional balance. In contrast, early injury
      affects fundamental development processes and alters the emerging organization
      and functioning of neural systems.

PMID- 22415922
TI  - Using knowledge of development to promote recovery of function after brain
      damage.
AB  - Knowledge of normal development of brain-behavior relations plays an important
      role in understanding how the plasticity of the nervous system can be used to
      promote recovery of function following brain damage. Aspects of the other
      articles in this issue are used in justification of the value of such
      developmental knowledge. Also, the development of amblyopia and its remediation
      in adulthood is discussed as a model for developing other techniques for ensuring
      recovery of function after stroke. Although the articles in this issue establish
      an excellent context for improving actual recovery of function (rather than
      compensation for deficits), much still needs to be discovered about how we can
      use developmental knowledge, along with knowledge of the plasticity of the
      nervous system, to improve remediation techniques.

PMID- 22415923
TI  - The reorganized brain: how treatment strategies for stroke and amblyopia can
      inform our knowledge of plasticity throughout the lifespan.
AB  - Neural plasticity plays a crucial role in human development. During development,
      neural networks are shaped by experience-dependent processes that selectively
      strengthen and prune connections so that those that remain match the environment
      and process it optimally. Over time, neural connections become more stable,
      forming widely distributed, interconnected networks involving balanced excitation
      and inhibition and structural stabilizers like myelin. It was long believed that
      the potential for organization or reorganization existed only during early
      development. However, the successful treatments for adults with stroke or
      amblyopia discussed in this issue suggest that the potential for significant
      reorganization persists well into adulthood. Thus, development can be thought of
      as the stabilization of connections to match the current environment but with
      considerable residual plasticity that can be revealed if there is a shift in the
      excitatory: inhibitory balance or the removal of the structural stabilizers.

PMID- 22415924
TI  - Organometallic ruthenium and iridium transfer-hydrogenation catalysts using
      coenzyme NADH as a cofactor.
AB  - Artificial enzymes: half-sandwich arene ruthenium(II) and cyclopentadienyl
      iridium(III) complexes containing N,N-chelated ligands can use NADH as a source
      of hydride for the reduction of ketones. Moreover, cyclopentadienyl
      phenanthroline iridium(III) derivatives at micromolar concentrations are robust
      catalysts for the production of H(2) from NADH in water and can raise the
      NAD(+)/NADH ratio in cancer cells.

PMID- 22415925
TI  - Clinical implication of an insufficient number of examined lymph nodes after
      curative resection for gastric cancer.
AB  - BACKGROUND: The seventh edition of the tumor, lymph node (LN), metastasis (TNM)
      staging system increased the required number of examined LNs in gastric cancer
      from 15 to 16. However, the same staging system defines lymph node-negative
      gastric cancer regardless of the number of examined LNs. In this study, the
      authors evaluated whether gastric cancer can be staged properly with fewer than
      15 examined LNs. METHODS: The survival rates of 10,010 patients who underwent
      curative gastrectomy from 1987 to 2007 were analyzed. The patients were divided
      into 2 groups according to the number of examined LNs, termed the "insufficient"
      group (<=15 examined LNs) and the "sufficient" group (>=16 examined LNs). The
      survival curves of patients from both groups were compared according to the
      seventh edition of the TNM classification. RESULTS: Three hundred sixteen
      patients (3.2%) had <=15 examined LNs for staging after they underwent standard,
      curative lymphadenectomy. Patients who had T1 tumor classification, N0 lymph node
      status, and stage I disease with an insufficient number of examined LNs after
      curative gastrectomy had a significantly worse prognosis than patients who had
      >=16 examined LNs. Moreover, having an insufficient number of examined LNs was an
      independent prognostic factor for patients who had T1, N0, and stage I disease.
      CONCLUSIONS: Lymph node-negative cancers in which <=15 LNs were examined,
      classified as N0 in the new TNM staging system, could not adequately predict
      patient survival after curative gastrectomy, especially in patients with early
      stage gastric cancer.

PMID- 22415926
TI  - Predictors of kidney biopsy complication among patients with systemic lupus
      erythematosus.
AB  - Kidney biopsy is essential for the diagnosis and management of lupus nephritis.
      The risk of bleeding complication, however, is not defined in the systemic lupus
      erythematosus population. A retrospective cohort study was conducted to determine
      predictors of major and minor complications among patients with systemic lupus
      erythematosus undergoing percutaneous ultrasound-guided kidney biopsy. Major
      complications included bleeding necessitating intervention, hypotension requiring
      vasopressors or higher level of care or death. Minor complications included
      moderate or large (>= 4 cm in largest diameter) perinephric hematoma, gross
      hematuria or voiding difficulties. All patients were observed for at least 23 h
      post-procedure. The overall incidence of bleeding was 10.5% (2.7% major, 7.8%
      minor). Adjusted logistic regression showed that for every 10,000 cells/mm(3)
      decrease in platelet count, risk for major and any complication increased by 27%
      (odds ratio 1.27; 95% confidence intervals 1.06-1.51; p = 0.01) and 8% (odds
      ratio 1.08; 95% confidence intervals 1.02-1.15; p = 0.01), respectively. Patients
      with a platelet count <150,000 cells/mm(3) were 30 times more likely to
      experience a major complication (p = 0.002). Other candidate predictors,
      including steroid exposure, kidney function, hematocrit and histopathology, were
      not significant. Kidney biopsies are well tolerated in patients with systemic
      lupus erythematosus. However, patients with pre-biopsy platelet counts <150,000
      cells/mm(3) are at markedly increased risk for a major bleeding complication.

PMID- 22415927
TI  - Microcirculation as determined by iontophoresis in SLE-patients and controls.
AB  - BACKGROUND: The risk of cardiovascular disease (CVD), microangiopathy and
      prevalence of atherosclerotic plaques are increased in Systemic Lupus
      Erythematosus (SLE). As systemic endothelial dysfunction is one of the earliest
      signs of these vascular outcomes in the general population we assessed skin
      microvascular endothelial function in SLE patients. METHODS: Endothelial function
      in skin was tested with local application of acetylcholine (inducing endothelium
      dependent vasodilatation) and any concomitant increase in skin perfusion was
      measured with Laser Doppler Fluxmetry (LDF) in 84 SLE-patients (83% women, mean
      age 47 years) and 81 age and sex matched controls. Common carotid intima-media
      thickness (cIMT) and plaque occurrence were also determined using B-mode
      ultrasound. RESULTS: There were no significant differences in skin microvascular
      endothelial function between SLE-patients and controls. In the SLE group,
      endothelial function did not vary in relation to skin manifestations, Raynaud's
      phenomenon, nephritis or plaque occurrence. In SLE patients with CVD, however,
      endothelial function was impaired. CONCLUSION: Skin microvascular endothelial
      function is associated with CVD but not with early signs of atherosclerosis in
      SLE-patients. The endothelial function is not different in SLE-patients as
      compared to controls.

PMID- 22415928
TI  - Human embryonic stem cells exhibit increased propensity to differentiate during
      the G1 phase prior to phosphorylation of retinoblastoma protein.
AB  - While experimentally induced arrest of human embryonic stem cells (hESCs) in G1
      has been shown to stimulate differentiation, it remains unclear whether the
      unperturbed G1 phase in hESCs is causally related to differentiation. Here, we
      use centrifugal elutriation to isolate and investigate differentiation
      propensities of hESCs in different phases of their cell cycle. We found that
      isolated G1 cells exhibit higher differentiation propensity compared with S and
      G2 cells, and they differentiate at low cell densities even under self-renewing
      conditions. This differentiation of G1 cells was partially prevented in dense
      cultures of these cells and completely abrogated in coculture with S and G2
      cells. However, coculturing without cell-to-cell contact did not rescue the
      differentiation of G1 cells. Finally, we show that the subset of G1 hESCs with
      reduced phosphorylation of retinoblastoma has the highest propensity to
      differentiate and that the differentiation is preceded by cell cycle arrest.
      These results provide direct evidence for increased propensity of hESCs to
      differentiate in G1 and suggest a role for neighboring cells in preventing
      differentiation of hESCs as they pass through a differentiation sensitive, G1
      phase.

PMID- 22415929
TI  - Highly efficient heterogeneous gold-catalyzed direct synthesis of tertiary and
      secondary amines from alcohols and urea.
AB  - Urea, the white gold: The efficient synthesis of tertiary and secondary amines is
      achieved by heterogeneous gold-catalyzed direct amination of stoichiometric
      alcohols with urea in good to excellent yields. Via a hydrogen autotransfer
      pathway, the reactions of primary alcohols with urea give tertiary amines
      exclusively, while secondary alcohols selectively afford secondary amines.

PMID- 22415930
TI  - Oxygen-bound Hell's gate globin I by classical versus LB nanotemplate method.
AB  - X-ray atomic structure of recombinant Hell's gate globin I (HGbI) from
      Methylacidophilum infernorum was calculated from the X-ray diffraction data of
      two different types of crystals: obtained by classical hanging drop and by LB
      nanotemplate method under the same crystallization conditions. After the accurate
      comparison of crystallographic parameters and electron density maps of two
      structures they appears to be quite similar, while the quality of the crystals
      grown by LB nanotemplate method was higher then of those grown by classical
      method. Indeed, the resolution of the LB crystal structure was 1.65 A, while
      classical crystals showed only 3.2 A resolution. Moreover, the reproducibility of
      this result in the case of LB crystals was much better-nine crystals from 10 gave
      the same structural results, while only two of 10 classical crystals were
      appropriate for the X-ray structure resolution.

PMID- 22415931
TI  - A novel polymorphic allele of human arylacetamide deacetylase leads to decreased
      enzyme activity.
AB  - Human arylacetamide deacetylase (AADAC) is responsible for the hydrolysis of
      clinically used drugs such as flutamide, phenacetin, and rifamycins. Our recent
      studies suggested that human AADAC is a relevant enzyme pharmacologically and
      toxicologically. To date, the genetic polymorphisms that affect enzyme activity
      in AADAC have been unknown. In this study, we found single-nucleotide
      polymorphisms in the human AADAC gene in a liver sample that showed remarkably
      low flutamide hydrolase activity. Among them, g.13651G > A (V281I) and g.14008T >
      C (X400Q) were nonsynonymous. The latter would be predicted to cause a C-terminal
      one-amino acid (glutamine) extension. The AADAC*2 allele (g.13651G > A) was found
      in all populations investigated in this study (European American, African
      American, Korean, and Japanese), at allelic frequencies of 52.6 to 63.5%, whereas
      the AADAC*3 allele (g.13651G > A/g.14008T > C) was found in European American
      (1.3%) and African American (2.0%) samples. COS7 cells expressing AADAC.1 (wild
      type) exhibited flutamide, phenacetin, and rifampicin hydrolase activities with
      intrinsic clearance (CLint) values of 1.31 +/- 0.06, 1.00 +/- 0.02, and 0.39 +/-
      0.02 MUl x min(-1) x unit(-1), respectively. AADAC.2, which is a protein produced
      from the AADAC*2 allele, showed moderately lower or similar CLint values,
      compared with AADAC.1, but AADAC.3 showed substantially lower CLint values
      (flutamide hydrolase, 0.21 +/- 0.02 MUl x min(-1) x unit(-1); phenacetin
      hydrolase, 0.12 +/- 0.00 MUl x min(-1) x unit(-1); rifampicin hydrolase, 0.03 +/-
      0.01 MUl x min(-1) x unit(-1), respectively). Microsomes from a liver sample
      genotyped as AADAC*3/AADAC*3 showed decreased enzyme activities, compared with
      those genotyped as AADAC*1/AADAC*1, AADAC*1/AADAC*2, and AADAC*2/AADAC*2. In
      conclusion, we found an AADAC allele that yielded decreased enzyme activity. This
      study should provide useful information on interindividual variations in AADAC
      enzyme activity.

PMID- 22415932
TI  - Drug interaction of efavirenz and midazolam: efavirenz activates the CYP3A
      mediated midazolam 1'-hydroxylation in vitro.
AB  - CYP3A4 and CYP3A5 are the most important drug-metabolizing enzymes. For several
      drugs, heteroactivation of CYP3A-mediated reactions has been demonstrated in
      vitro. In vivo data suggested a possible acute activation of CYP3A4-catalyzed
      midazolam metabolism by efavirenz. Therefore, we aimed to investigate the effect
      of efavirenz on the in vitro metabolism of midazolam. The formation of 1'
      hydroxymidazolam was studied in pooled human liver microsomes (HLM) and
      recombinant human CYP3A4 and CYP3A5 (rCYP3A4 and rCYP3A5) in the presence of
      efavirenz (0.5, 1, and 5 MUM). Product formation rates (V(max)) increased with
      increasing efavirenz concentrations (~1.5-fold increase at 5 MUM efavirenz in HLM
      and ~1.4-fold in rCYP3A4). The activation in rCYP3A4 was dependent on cytochrome
      b5, and the activating effect was also observed in rCYP3A5 supplemented with
      cytochrome b5, where Vmax was ~1.3-fold enhanced. Concomitant inhibition of CYP3A
      activity with ketoconazole in HLM abolished the increase in the 1'
      hydroxymidazolam formation rate, further confirming involvement of CYP3A. The
      results of this study represent a distinct acute activation of midazolam
      metabolism and support the in vivo observations. Moreover, only efavirenz, but
      not its major metabolite 8-hydroxyefavirenz, was responsible for the activation.
      The increase in 1'-hydroxymidazolam formation may have been caused by binding of
      efavirenz to a peripheral site of the enzyme, leading to enhanced midazolam
      turnover due to changes at the active site.

PMID- 22415933
TI  - Transport of the coumarin metabolite 7-hydroxycoumarin glucuronide is mediated
      via multidrug resistance-associated proteins 3 and 4.
AB  - Coumarin (1,2-benzopyrone) is a natural compound that has been used as a
      fragrance in the food and perfume industry and could have therapeutic usefulness
      in the treatment of lymphedema and different types of cancer. Several previous
      pharmacokinetic studies of coumarin have been performed in humans, which revealed
      extensive first-pass metabolism of the compound. 7-Hydroxycoumarin (7-HC) and its
      glucuronide (7-HC-G) are the main metabolites formed in humans, and via this
      route, 80 to 90% of the absorbed coumarin is excreted into urine, mainly as 7-HC
      G. Active transport processes play a role in the urinary excretion of 7-HC-G;
      however, until now, the transporters involved remained to be elucidated. In this
      study, we investigated whether the efflux transporters multidrug resistance
      associated proteins (MRP)1-4, breast cancer resistance protein, or P-glycoprotein
      play a role in 7-HC and 7-HC-G transport. For this purpose, we measured uptake of
      the metabolites into membrane vesicles overexpressing these transporters. Our
      results showed that 7-HC is not transported by any of the efflux transporters
      tested, whereas 7-HC-G was a substrate of MRP3 and MRP4. These results are in
      line with the pharmacokinetic profile of coumarin and suggest that MRP3 and MRP4
      are the main transporters involved in the excretion of the coumarin metabolite 7
      HC-G from liver and kidney.

PMID- 22415934
TI  - The identification and internal validation of a preoperative serum biomarker
      panel to determine extracapsular extension in patients with prostate cancer.
AB  - BACKGROUND: Accurate preoperative staging of prostate cancer (PCa) is important
      but current diagnostic methods cannot accurately determine extracapsular
      extension (ECE), resulting in the possible triage of patients towards a less
      appropriate arm of therapy. This has consequences to patient care and better
      methods of preoperatively determining ECE are required. METHODS: We followed a
      biomarker development pathway and compared the preoperative serum expressions of
      VEGF-D, PEDF, IGF-I, IGFBP3, and CD14 in patients from the Irish Prostate Cancer
      Research Consortium (PCRC) with radical prostatectomy determined ECE against
      patients with nonECE. RESULTS: The expression measurements of five proteins were
      fitted into a logistic regression model and backwards variable elimination
      methods were applied which resulted in a model with IGFBP3 and CD14 as the best
      combination biomarker panel. This panel was tested in an independent cohort of
      patients using an optimized multiplex electrochemiluminescence assay. Receiver
      operating characteristic curves were generated and the areas under the curve
      (AUC) were calculated as an estimation of prediction accuracy. The biomarker
      panel was validated with an AUC of 76.6%, and a sensitivity and specificity of
      80% and 75% was obtained. CONCLUSIONS: This is the first internally validated,
      preoperative serum biomarker panel that identifies ECE in patients with Gleason
      score 7 PCa with AUC 76.6%. The panel surpasses the routinely used diagnostic
      standards in accuracy and may help to improve preoperative cancer staging, better
      inform treatment options, and improve the referral patterns of patients with
      urgently treatable cancers towards more appropriate arms of therapy.

PMID- 22415935
TI  - Can we, and do we need to, define bladder neck hypermobility and intrinsic
      sphincteric deficiency? ICI-RS 2011.
AB  - AIMS: Bladder neck hypermobility (BNH, also called urethral hypermobility), and
      intrinsic sphincteric deficiency (ISD) are terms frequently used in the clinical
      evaluation and management of stress urinary incontinence, and as subject
      qualifiers in clinical research. The terms also infer pathophysiologic concepts,
      as BNH and ISD appear to represent two different aspects of failure of the
      continence mechanism. Unfortunately, neither term is well-defined, and the
      various clinical and urodynamic characterizations of these terms do not correlate
      well with one another. METHODS: The value of these concepts and these specific
      terms was debated at the ICI-RS meeting, Bristol, UK, June 2011. Two clinicians
      were asked to take opposing viewpoints, with three weeks lead-time prior to the
      meeting. Each discussant presented one viewpoint, "for" or "against," followed by
      a brief discussion to review the presentations. RESULTS: The consensus was that,
      while we currently cannot adequately define these terms, there is a need to
      develop terminology employing these concepts. CONCLUSIONS: Terminology should
      permit improved definition of the sphincteric mechanism, allow individual patient
      characterization and serve as useful waypoints in treatment decisions.

PMID- 22415936
TI  - [Pd(IPr*)(cinnamyl)Cl]: an efficient pre-catalyst for the preparation of tetra
      ortho-substituted biaryls by Suzuki-Miyaura cross-coupling.
AB  - The bigger the better: The new well-defined [Pd(IPr*)(cin)Cl] pre-catalyst is
      described. This complex proves to be highly active in the Suzuki-Miyaura cross
      coupling for the synthesis of tetra-ortho-substituted biaryls under mild
      conditions. IPr* is reported as the largest N-heterocyclic carbene (NHC) to date
      for [Pd(NHC)(cin)Cl] complexes, explaining the high reactivity observed for this
      complex in this challenging transformation.

PMID- 22415937
TI  - Misuse of DeLong test to compare AUCs for nested models.
AB  - The area under the receiver operating characteristics curve (AUC of ROC) is a
      widely used measure of discrimination in risk prediction models. Routinely, the
      Mann-Whitney statistics is used as an estimator of AUC, while the change in AUC
      is tested by the DeLong test. However, very often, in settings where the model is
      developed and tested on the same dataset, the added predictor is statistically
      significantly associated with the outcome but fails to produce a significant
      improvement in the AUC. No conclusive resolution exists to explain this finding.
      In this paper, we will show that the reason lies in the inappropriate application
      of the DeLong test in the setting of nested models. Using numerical simulations
      and a theoretical argument based on generalized U-statistics, we show that if the
      added predictor is not statistically significantly associated with the outcome,
      the null distribution is non-normal, contrary to the assumption of DeLong test.
      Our simulations of different scenarios show that the loss of power because of
      such a misuse of the DeLong test leads to a conservative test for small and
      moderate effect sizes. This problem does not exist in cases of predictors that
      are associated with the outcome and for non-nested models. We suggest that for
      nested models, only the test of association be performed for the new predictors,
      and if the result is significant, change in AUC be estimated with an appropriate
      confidence interval, which can be based on the DeLong approach.

PMID- 22415940
TI  - Visible-light-promoted stereoselective alkylation by combining heterogeneous
      photocatalysis with organocatalysis.

PMID- 22415941
TI  - Production of biohydrogen by aqueous phase reforming of polyols over platinum
      catalysts supported on three-dimensionally bimodal mesoporous carbon.
AB  - Now in 3D! Three-dimensionally bimodal carbons (3D-BMC) with mesopores of tunable
      size (controlled through the polymerization of the carbon precursor) are
      synthesized. After loading with platinum, the catalysts are used in aqueous phase
      reforming of polyols, and show superior performance in terms of carbon
      conversion, hydrogen yield, selectivity, and hydrogen production rate compared to
      platinum catalysts supported on activated carbon or two-dimensional CMK-3.

PMID- 22415942
TI  - Lumbar intraspinal injection of neural stem cells in patients with amyotrophic
      lateral sclerosis: results of a phase I trial in 12 patients.
AB  - Advances in stem cell biology have generated intense interest in the prospect of
      transplanting stem cells into the nervous system for the treatment of
      neurodegenerative diseases. Here, we report the results of an ongoing phase I
      trial of intraspinal injections of fetal-derived neural stems cells in patients
      with amyotrophic lateral sclerosis (ALS). This is a first-in-human clinical trial
      with the goal of assessing the safety and tolerability of the surgical procedure,
      the introduction of stem cells into the spinal cord, and the use of
      immunosuppressant drugs in this patient population. Twelve patients received
      either five unilateral or five bilateral (10 total) injections into the lumbar
      spinal cord at a dose of 100,000 cells per injection. All patients tolerated the
      treatment without any long-term complications related to either the surgical
      procedure or the implantation of stem cells. Clinical assessments ranging from 6
      to 18 months after transplantation demonstrated no evidence of acceleration of
      disease progression due to the intervention. One patient has shown improvement in
      his clinical status, although these data must be interpreted with caution since
      this trial was neither designed nor powered to measure treatment efficacy. These
      results allow us to report success in achieving the phase I goal of demonstrating
      safety of this therapeutic approach. Based on these positive results, we can now
      advance this trial by testing intraspinal injections into the cervical spinal
      cord, with the goal of protecting motor neuron pools affecting respiratory
      function, which may prolong life for patients with ALS.

PMID- 22415943
TI  - Novel Polypyridyl chelators deplete cellular zinc and destabilize the X-linked
      inhibitor of apoptosis protein (XIAP) prior to induction of apoptosis in human
      prostate and breast cancer cells.
AB  - X-linked inhibitor of apoptosis protein (XIAP), inhibits the initiation and
      execution phases of the apoptotic pathway. XIAP is the most potent member of the
      inhibitor of apoptosis protein (IAP) family of the endogenous caspase inhibitors.
      Therefore, targeting XIAP may be a promising strategy for the treatment of
      apoptosis-resistant malignancies. In this study, we systematically studied the
      relationships of chemical structures of several novel ligands to their zinc (Zn)
      binding ability, molecular target XIAP, and tumor cell death-inducing activity.
      We show that treatment of PC-3 prostate cancer and MDA-MB-231 breast cancer cells
      with these membrane-permeable Zn-chelators with different Zn affinities results
      in varying degrees of XIAP depletion. Following decreased level of XIAP
      expression, we also show apoptosis-related caspase activation and cellular
      morphological changes upon treatment with strong Zn-chelators N4Py and BnTPEN.
      Addition of Zn has a full protective effect on the cells treated with these
      chelators, while iron (Fe) addition has only partial protection that, however,
      can be further increased to a comparable level of protection as Zn by inhibition
      of ROS generation, indicating that cell death effects mediated by Fe- but not Zn
      complexes involve redox cycling. These findings suggest that strong Zn-chelating
      agents may be useful in the treatment of apoptosis-resistant human cancers.

PMID- 22415945
TI  - Pathological findings at radical prostatectomy in patients initially managed by
      active surveillance: a comparative analysis.
AB  - BACKGROUND: The purpose of our analysis was to determine if delays in treatment
      caused by active surveillance result in significant pathological changes when
      patients no longer meet the criteria on repeat biopsy and to study whether or not
      these changes may affect treatment outcomes. METHODS: Out of 207 men who were on
      active surveillance, 47 (23%) no longer met the criteria after one of the repeat
      biopsies. Twenty-two underwent radical prostatectomy at our institution and
      formed the main group (Group 1) of this study. One hundred sixty-four patients
      met the criteria for active surveillance but underwent immediate surgery. Of
      these patients, we selected 38 (23%) with the lowest predicted biochemical
      recurrence-free survival. These patients formed the comparison group (Group 2).
      Pathological features as well as postoperative biochemical outcomes were compared
      between the groups. RESULTS: Seven patients (32%) in Group 1 and four (11%) in
      Group 2 have predominantly high-grade cancer (i.e., >=4/5 + 3) at pathology. The
      visually estimated percent of carcinoma was also higher in patients initially
      managed by active surveillance (median 12.5 vs. 5.0 in Groups 1 and 2,
      respectively, P = 0.009). Other pathological characteristics were similar in both
      groups. With limited duration of follow-up, postoperative biochemical recurrence
      free survival did not differ significantly between the groups. CONCLUSIONS: Our
      study has demonstrated that both tumor grade and volume may increase during
      active surveillance. However, the clinical significance of these changes with
      respect to the outcomes of delayed treatment remains to be established.

PMID- 22415944
TI  - Light and heavy touch reduces postural sway and modifies axial tone in
      Parkinson's disease.
AB  - BACKGROUND: Light touch with a stable object reduces postural sway by increasing
      axial postural tone in healthy subjects. However, it is unknown whether subjects
      with Parkinson's disease (PD), who have more postural sway and higher axial
      postural tone than healthy subjects, can benefit from haptic touch. OBJECTIVE: To
      investigate the effect of light and heavy touch on postural stability and hip
      tone in subjects with PD. METHODS: Fourteen subjects with mid-stage PD and 14
      healthy control subjects were evaluated during quiet standing with eyes closed
      with their arms (a) crossed, (b) lightly touching a fixed rigid bar in front of
      them, and (c) firmly gripping the bar. Postural sway was measured with a
      forceplate, and axial hip tone was quantified using a unique device that measures
      the resistance of the hips to yaw rotation while maintaining active stance.
      RESULTS: Subjects with PD significantly decreased their postural sway with light
      or heavy touch (P < .001 vs arms crossed), similarly as control subjects. Without
      touch, hip tone was larger in PD subjects. With touch, however, tone values were
      similar in both groups. This change in hip tone with touch was highly correlated
      with the initial amount of tone (PD, r = -.72 to -.95; controls, r = -.74 to 
      .85). CONCLUSIONS: The authors showed, for the first time, that subjects with PD
      benefit from touch similarly to control subjects and that despite higher axial
      postural tone, PD subjects are able to modulate their tone with touch. Future
      studies should investigate the complex relationship between touch and postural
      tone.

PMID- 22415946
TI  - A boradiazaindacene-based turn-on fluorescent probe for cyanide detection in
      aqueous media.
AB  - Turn on events: A molecular probe consisting of a boradiazaindacene unit
      conjugated with a dicyano-vinyl group has been designed for the selective and
      sensitive detection of cyanide by strong fluorescence enhancement in aqueous
      media (see scheme).

PMID- 22415947
TI  - Can we identify men who will have complications from benign prostatic obstruction
      (BPO)? ICI-RS 2011.
AB  - AIMS: This ICI-RS report aims to analyze morphological or functional
      complications of the lower or upper urinary tract in elderly men, clarify the
      association between complications and benign prostatic obstruction (BPO) and
      define men who will develop these complications. Research proposals to further
      enlighten these associations were to be defined. METHODS: A think-tank discussion
      was held on the annual ICI-RS meeting in 2011. The published literature between
      1966 and 2011 was reviewed and research proposals were defined with all congress
      participants. RESULTS: Post-void residual, bladder diverticula or calculi, vesico
      ureteral reflux, hydronephrosis, renal insufficiency, and urinary retention
      appear with greater prevalence in patients with symptoms or signs of benign
      prostatic hyperplasia. BPO may directly or indirectly be responsible for these
      complications but conclusive evidence for BPO as the primary cause does not
      exist. Many of the complications have a multifactorial etiology and BPO is only
      partially responsible. It is currently impossible to define men who will develop
      complications. CONCLUSIONS: In contrast to the widespread belief of urologist,
      there is only rudimentary data available showing no convincing association
      between urinary tract complications and BPO. The ICI-RS proposes that prospective
      trials are conducted to demonstrate the association between complications and BPO
      by using cystometry, pressure-flow (P/F) studies, and other commonly used BPO
      parameters in men with complications and comparing those with a cohort of age
      matched men without complications. Non-invasive proxy parameters of BPO, for
      example, ultrasonic measurement of detrusor wall thickness, can be used instead
      of P/F studies especially in longitudinal trials.

PMID- 22415948
TI  - The effect of cluster size imbalance and covariates on the estimation performance
      of quadratic inference functions.
AB  - Generalized estimating equations (GEE) are commonly used for the analysis of
      correlated data. However, use of quadratic inference functions (QIFs) is becoming
      popular because it increases efficiency relative to GEE when the working
      covariance structure is misspecified. Although shown to be advantageous in the
      literature, the impacts of covariates and imbalanced cluster sizes on the
      estimation performance of the QIF method in finite samples have not been studied.
      This cluster size variation causes QIF's estimating equations and GEE to be in
      separate classes when an exchangeable correlation structure is implemented,
      causing QIF and GEE to be incomparable in terms of efficiency. When utilizing
      this structure and the number of clusters is not large, we discuss how covariates
      and cluster size imbalance can cause QIF, rather than GEE, to produce estimates
      with the larger variability. This occurrence is mainly due to the empirical
      nature of weighting QIF employs, rather than differences in estimating equations
      classes. We demonstrate QIF's lost estimation precision through simulation
      studies covering a variety of general cluster randomized trial scenarios and
      compare QIF and GEE in the analysis of data from a cluster randomized trial.

PMID- 22415949
TI  - Ruthenium-catalyzed [2+2+2] cycloaddition of diynes with nitriles in pure water.
AB  - One ring to bind them: An efficient method for synthesizing highly functionalized
      pyridine derivatives from diynes and nitriles is described. The reaction system
      involves Cp*Ru(COD)Cl/tppts-catalyzed [2+2+2] cycloaddition in pure water.
      Without being accompanied by diyne dimerization or trimerization byproducts, the
      desired products can be obtained in moderate to high yields.

PMID- 22415950
TI  - Mesoporous Au/TiO2 nanocomposite microspheres for visible-light photocatalysis.
AB  - Mesoporous Au/TiO(2) nanocomposite microspheres have been synthesized by using a
      microemulsion-based bottom-up self-assembly (EBS) process starting from
      monodisperse gold and titania nanocrystals as building blocks. The microspheres
      had large surface areas (above 270 m(2) g(-1)) and open mesopores (about 5 nm),
      which led to the adsorption-driven concentration of organic molecules in the
      vicinity of the microspheres. Au nanoparticles, which were stably confined within
      the microspheres, enhanced the absorption over the broad UV/Vis/NIR spectroscopic
      range, owing to their strong surface plasmon resonance (SPR); as a result, the Au
      nanoparticles promoted the visible-light photo-induced degradation of organic
      compounds.

PMID- 22415951
TI  - Neurotrophic bone marrow cellular nests prevent spinal motoneuron degeneration in
      amyotrophic lateral sclerosis patients: a pilot safety study.
AB  - The objective of this article is to assess the safety of intraspinal infusion of
      autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for
      histopathological signs of cellular neurotrophism in amyotrophic lateral
      sclerosis (ALS) patients. We conducted an open single arm phase I trial. After 6
      months observation, autologous BMNCs were infused into the posterior spinal cord
      funiculus. Safety was the primary endpoint and was defined as the absence of
      serious transplant-related adverse events. In addition, forced vital capacity
      (FVC), ALS-functional rating scale (ALS-FRS), Medical Research Council scale for
      assessment of muscle power (MRC), and Norris scales were assessed 6 and 3 months
      prior to the transplant and quarterly afterward for 1 year. Pathological studies
      were performed in case of death. Eleven patients were included. We did not
      observe any severe transplant-related adverse event, but there were 43 nonsevere
      events. Twenty-two (51%) resolved in <=2 weeks and only four were still present
      at the end of follow-up. All were common terminology criteria for adverse events
      grade <=2. No acceleration in the rate of decline of FVC, ALS-FRS, Norris, or MRC
      scales was observed. Four patients died on days 359, 378, 808, and 1,058 post
      transplant for reasons unrelated to the procedure. Spinal cord pathological
      analysis showed a greater number of motoneurons in the treated segments compared
      with the untreated segments (4.2 +/- 0.8 motoneurons per section [mns per sect]
      and 0.9 +/- 0.3 mns per sect, respectively). In the treated segments, motoneurons
      were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits.
      This clinical trial confirms not only the safety of intraspinal infusion of
      autologous BMNC in ALS patients but also provides evidence strongly suggesting
      their neurotrophic activity.

PMID- 22415952
TI  - Fever and haemoptysis in an injecting drug user.

PMID- 22415953
TI  - Who is shaping the future of European health systems?

PMID- 22415954
TI  - Will your telomeres tell your future?

PMID- 22415955
TI  - Whistleblower lawsuit claims Takeda concealed harms of diabetes drug.

PMID- 22415956
TI  - Teenage smoking is an "epidemic," says US surgeon general.

PMID- 22415957
TI  - Liberal Democrats vent opposition to health reforms in England but fail to "kill
      the bill".

PMID- 22415958
TI  - Anaesthetics journals retract further articles after ethics approval is found
      lacking.

PMID- 22415959
TI  - High Court quashes GMC's findings that psychiatrist abused his position.

PMID- 22415960
TI  - Genetic manipulation of crops could offer healthier food, say scientists.

PMID- 22415961
TI  - Man is granted right to seek declaration allowing a doctor to kill him.

PMID- 22415962
TI  - Bis(imidazolium) L-tartrate: a hydrogen-bonded displacive-type molecular
      ferroelectric material.
AB  - A hydrogen-bonded ionic cocrystal with imidazole as molecular rotator and L
      tartaric acid as homochiral component is reported as a displacive-type
      ferroelectric material. It undergoes a paraelectric-ferroelectric phase
      transition at 252 K with exceptional dielectric responses triggered by atomic
      displacements.

PMID- 22415963
TI  - Structural evolution and functional diversification analyses of argonaute
      protein.
AB  - Argonaute (AGO) proteins are highly specialized small-RNA-binding modules and
      small RNAs are anchored to their specific binding pockets guiding AGO proteins to
      target mRNA molecules for silencing or destruction. The 135 full-length AGO
      protein sequences derived from 36 species covering prokaryote, archaea, and
      eukaryote are chosen for structural and functional analyses. The results show
      that bacteria and archaeal AGO proteins are clustered in the same clade and there
      exist multiple AGO proteins in most eukaryotic species, demonstrating that the
      increase of AGO gene copy number and horizontal gene transfer (HGT) have been the
      main evolutionary driving forces for adaptability and biodiversity. And the
      emergence of PAZ domain in AGO proteins is the unique evolutionary event. The
      analysis of middle domain (MID)-nucleotide contaction shows that either the
      position of sulfate I bond in Nc_QDE2 or the site of phosphate I bond in Hs_AGO2
      represents the 5'-nucleotide binding site of miRNA. Also, H334, T335, and Y336 of
      Hs_AGO1 can form hydrogen bonds with 3'-overhanging ends of miRNAs and the same
      situation exists in Hs_AGO2, Hs_AGO3, Hs_AGO4, Dm_AGO1, and Ce_Alg1. Some PIWI
      domains containing conserved DDH motif have no slicer activity, and post
      translational modifications may be associated with the endonucleolytic activities
      of AGOs. With the numbers of AGO genes increasing and fewer crystal structures
      available, the evolutionary and functional analyses of AGO proteins can help
      clarify the molecular mechanism of function diversification in response to
      environmental changes, and solve major issues including host defense mechanism
      against virus infection and molecular basis of disease.

PMID- 22415964
TI  - Improved lithium cyclability and storage in mesoporous SnO2 electronically wired
      with very low concentrations (<=1 %) of reduced graphene oxide.
AB  - On the wire: Mesoporous tin dioxide (SnO(2)) wired with very low amounts (<=1 %)
      of reduced graphene oxide (rGO) exhibits a remarkable improvement in lithium-ion
      battery performance over bare mesoporous or solid nanoparticles of SnO(2).
      Reversible lithium intercalation into SnO(2)/SnO over several cycles was
      demonstrated in addition to conventional reversible lithium storage by an
      alloying reaction.

PMID- 22415965
TI  - Does diabetes mellitus-induced bladder remodeling affect lower urinary tract
      function? ICI-RS 2011.
AB  - AIMS: Due to an increase in aging population and changing eating habits diabetes
      mellitus (DM) type II is a rapidly increasing condition worldwide. Although not
      so detrimental as other co-morbidities, uropathy contributes to a significantly
      reduced quality-of-life in those affected. The purpose of this ICS-RS report is
      to highlight clinical and basic research data to outline directions for further
      research and possible treatment approaches. METHODS: This report is based on a
      think tank presentation and discussion at the ICI-RS 2011, original research data
      and literature research. RESULTS: Clinical and experimental data confirm that
      detrusor overactivity, both neurogenic and myogenic, and changes in transmitter
      regulation leading to a hyper- excitability of the detrusor are the major
      findings in diabetic neuropathic bladders. These findings seem to be related to
      an earlier stage of DM, whereas detrusor underactivity appears to be linked to
      later stages of DM. Detrusor smooth muscle cells seem to be modulated directly by
      hyperglycemia. Data support the theory that hyperglycemia-induced oxidative
      stress in the detrusor smooth muscle and that micro- and macrovascular events are
      also responsible for urologic complications of DM. CONCLUSIONS: DM causes bladder
      remodelling leading to uropathy in a mulitfactorial way. Future research should
      focus on the effects of DM as a function of time and develop novel animal models
      looking at defined aspects as well as interaction of different aspects- such as
      oxidative stress in neurogenic, myogenic and urothelial components and the role
      of inflammation and hypoxia caused by vascular complications.

PMID- 22415966
TI  - A Bayesian-frequentist two-stage single-arm phase II clinical trial design.
AB  - It is well-known that both frequentist and Bayesian clinical trial designs have
      their own advantages and disadvantages. To have better properties inherited from
      these two types of designs, we developed a Bayesian-frequentist two-stage single
      arm phase II clinical trial design. This design allows both early acceptance and
      rejection of the null hypothesis ( H(0) ). The measures (for example probability
      of trial early termination, expected sample size, etc.) of the design properties
      under both frequentist and Bayesian settings are derived. Moreover, under the
      Bayesian setting, the upper and lower boundaries are determined with predictive
      probability of trial success outcome. Given a beta prior and a sample size for
      stage I, based on the marginal distribution of the responses at stage I, we
      derived Bayesian Type I and Type II error rates. By controlling both frequentist
      and Bayesian error rates, the Bayesian-frequentist two-stage design has special
      features compared with other two-stage designs.

PMID- 22415967
TI  - A bond path and an attractive Ehrenfest force do not necessarily indicate bonding
      interactions: case study on M2X2 (M = Li, Na, K; X = H, OH, F, Cl).
AB  - Interactions in dimers of model alkali metal derivatives M(2)X(2) (M = Li or Na
      or K; X = H or F, Cl, OH) are studied in the frame of the quantum theory of atoms
      in molecules (QTAIM) using the interacting quantum atoms approach (IQA). Contrary
      to opinion prevalent in QTAIM studies, the interaction between two anions linked
      by a bond path is demonstrated to be strongly repulsive. One may therefore say
      that a bond path does not necessarily indicate bonding interactions. The
      interactions between two anions or two cations that are not linked by a bond path
      are also strongly repulsive. The repulsive anion-anion and cation-cation
      interactions are outweighed by much stronger attractive anion-cation
      interactions, and the model molecules are therefore in a stable state. The
      attractive Ehrenfest forces (calculated in the frame of the QTAIM) acting across
      interatomic surfaces shared by anions in the dimers do not reflect the repulsive
      interactions between anions. Probable reasons of this disagreement are discussed.
      The force exerted on the nucleus and the electrons of a particular atom by the
      nucleus and the electrons of any another atom in question is proposed. It is
      assumed that this force unambiguously exposes whether basins of two atoms are
      attracted or repelled by each other in a polyatomic molecule.

PMID- 22415968
TI  - Polo-like kinase 1 inhibition kills glioblastoma multiforme brain tumor cells in
      part through loss of SOX2 and delays tumor progression in mice.
AB  - Glioblastoma multiforme (GBM) ranks among the deadliest types of cancer and given
      these new therapies are urgently needed. To identify molecular targets, we
      queried a microarray profiling 467 human GBMs and discovered that polo-like
      kinase 1 (PLK1) was highly expressed in these tumors and that it clustered with
      the proliferative subtype. Patients with PLK1-high tumors were more likely to die
      from their disease suggesting that current therapies are inactive against such
      tumors. This prompted us to examine its expression in brain tumor initiating
      cells (BTICs) given their association with treatment failure. BTICs isolated from
      patients expressed 110-470 times more PLK1 than normal human astrocytes.
      Moreover, BTICs rely on PLK1 for survival because the PLK1 inhibitor BI2536
      inhibited their growth in tumorsphere cultures. PLK1 inhibition suppressed
      growth, caused G(2) /M arrest, induced apoptosis, and reduced the expression of
      SOX2, a marker of neural stem cells, in SF188 cells. Consistent with SOX2
      inhibition, the loss of PLK1 activity caused the cells to differentiate based on
      elevated levels of glial fibrillary acidic protein and changes in cellular
      morphology. We then knocked glial fibrillary acidic protein (GFAP) down SOX2 with
      siRNA and showed that it too inhibited cell growth and induced cell death.
      Likewise, in U251 cells, PLK1 inhibition suppressed cell growth, downregulated
      SOX2, and induced cell death. Furthermore, BI2536 delayed tumor growth of U251
      cells in an orthotopic brain tumor model, demonstrating that the drug is active
      against GBM. In conclusion, PLK1 level is elevated in GBM and its inhibition
      restricts the growth of brain cancer cells.

PMID- 22415969
TI  - Superior herniation of the mediastinum presenting as an anterior neck mass on
      straining.
AB  - We report an infant with an anterior neck mass present only on straining. Airway
      fluoroscopy revealed this to be due to superior mediastinal herniation. Neck
      masses apparent only during Valsalva maneuver are rare and awareness of the
      differential diagnosis is important to avoid unnecessary investigation or
      surgery.

PMID- 22415970
TI  - Resveratrol chemosensitizes breast cancer cells to melphalan by cell cycle
      arrest.
AB  - Melphalan (MEL) is a chemotherapeutic agent used in breast cancer therapy;
      however, MEL's side effects limit its clinical applications. In the last 20
      years, resveratrol (RSV), a polyphenol found in grape skins, has been proposed to
      reduce the risk of cancer development. The aim of this study was to investigate
      whether RSV would be able to enhance the antitumor effects of MEL in MCF-7 and
      MDA-MB-231 cells. RSV potentiated the cytotoxic effects of MEL in human breast
      cancer cells. This finding was related to the ability of RSV to sensitize MCF-7
      cells to MEL-induced apoptosis. The sensitization by RSV involved the enhancement
      of p53 levels, the decrease of procaspase 8 and the activation of caspases 7 and
      9. Another proposed mechanism for the chemosensitization effect of MCF-7 cells to
      MEL by RSV was the cell cycle arrest in the S phase. The treatment with RSV or
      MEL increased the levels of p-Chk2. The increase became pronounced in the
      combined treatments of the compounds. The expression of cyclin A was decreased by
      treatment with RSV and by the combination of RSV with MEL. While the levels of
      cyclin dependent kinase 2 (CDK2) remained unchanged by treatments, its active
      form (Thr(160) -phosphorylated CDK2) was decreased by treatment with RSV and by
      the combination of RSV with MEL. The activity of CDK7, kinase that phosphorylates
      CDK2 at Thr(160), was inhibited by RSV and by the combination of RSV with MEL.
      These results indicate that RSV could be used as an adjuvant agent during breast
      cancer therapy with MEL.

PMID- 22415971
TI  - A direct catalytic asymmetric aldol reaction of alpha-sulfanyl lactones:
      efficient synthesis of SPT inhibitors.

PMID- 22415972
TI  - Pooled-testing procedures for screening high volume clinical specimens in
      heterogeneous populations.
AB  - Pooled testing is a procedure commonly used to reduce the cost of screening a
      large number of individuals for infectious diseases. In its simplest form, pooled
      testing works by compositing a set of individual specimens (e.g., blood or urine)
      into a common pool. If the pool tests negative, all individuals within it are
      diagnosed as negative. If the pool tests positive, retesting is needed to decode
      the positive individuals from the negative individuals. Traditionally, pooled
      testing has assumed that each individual has the same probability of being
      positive. However, this assumption is often unrealistic, especially when known
      risk factors can be used to measure distinct probabilities of positivity for each
      individual. In this paper, we investigate new pooled-testing algorithms that
      exploit the heterogeneity among individual probabilities and subsequently reduce
      the total number of tests needed, while maintaining accuracy levels similar to
      standard algorithms that do not account for heterogeneity. We apply these
      algorithms to data from the Infertility Prevention Project, a nationally
      implemented program supported by the Centers for Disease Control and Prevention.

PMID- 22415973
TI  - Chiral discrimination of aliphatic amines and amino alcohols using NMR
      spectroscopy.
AB  - Two methods are compared for analyzing the enantiomeric purity of aliphatic
      amines and amino alcohols using NMR spectroscopy. The first employs (+)-(18-crown
      6)-2,3,11,12-tetracarboxylic acid as a chiral NMR solvating agent in methanol
      d(4) . The second involves a derivatization scheme in which the amine is reacted
      with naphtho[2,3-c]furan-1,3-dione to form the corresponding amide. The naphthyl
      amide is then mixed with a chiral calix[4]resorcinarene in deuterium oxide. The
      crown ether only produces sufficient enantiomeric discrimination to determine
      enantiomeric purity for three of the nine substrates studied. The system with the
      naphthyl amide and a calix[4]resorcinarene produces enantiomeric discrimination
      of sufficient magnitude to determine enantiomeric purity for all nine substrates.
      The H1 and H4 resonances of the naphthyl ring are especially suitable to monitor
      for enantiomeric discrimination. The order of the (R)- and (S)-enantiomers of the
      H1 and H4 resonances exhibit specific trends for aliphatic amines and amino
      alcohols that correlate with the absolute configuration.

PMID- 22415974
TI  - Full characterization of colloidal solutions of long-alkyl-chain-amine-stabilized
      ZnO nanoparticles by NMR spectroscopy: surface state, equilibria, and affinity.
AB  - Full NMR characterization of ZnO nanoparticles (NPs) stabilized by various amines
      (hexadecylamine, dodecylamine, and octylamine) in C(7)D(8) demonstrated that the
      surface of this apparently simple system was very complex. Using different NMR
      spectroscopic techniques ((1)H, PGSE-NMR, diffusion-filtered (1)H NMR, NOESY,
      ROESY), we observed at least three different modes of interaction of the amines
      at the surface of the NPs, in thermodynamic equilibrium with the free amines, the
      relative populations of which varied with their concentration. The first mode
      corresponded to a strong interaction between a small amount of amine and the ZnO
      NPs (k(desorp)~13 s(-1)). The second mode corresponded to a weak interaction
      between the amines and the surface of the ZnO NPs (k(off(2))~50-60 s(-1)). The
      third, and weakest, mode of interaction corresponded to the formation of a second
      ligand shell by the amine around the NPs that was held together through van der
      Waals interactions (k(off(1))~25*10(5) s(-1)). The second and third modes were in
      fast exchange on the NMR timescales with the free amines. The strongly
      interacting amines at the NPs surface (first mode) were in slow exchange with the
      other modes. A complex hydrogen-bonding network at the NPs surface was also
      observed, which did not only involve the coordinated amine but also THF and water
      molecules that remained from the synthesis.

PMID- 22415975
TI  - Sp1, acetylated histone-3 and p300 regulate TRAIL transcription: mechanisms of
      PDGF-BB-mediated VSMC proliferation and migration.
AB  - We recently reported that TNF-related apoptosis-inducing ligand (TRAIL) is
      important in atherogenesis, since it can induce vascular smooth muscle cell
      (VSMC) proliferation and arterial thickening following injury. Here we show the
      first demonstrate that TRAIL siRNA reduces platelet-derived growth factor-BB
      (PDGF-BB)-stimulated VSMC proliferation and migration. PDGF-BB-inducible VSMC
      proliferation was completely inhibited in VSMCs isolated from aortas of TRAIL(-/
      ) mice; whereas inducible migration was blocked compared to control VSMCs. TRAIL
      transcriptional control mediating this response is not established. TRAIL mRNA,
      protein and promoter activity was increased by PDGF-BB and subsequently inhibited
      by dominant-negative Sp1, suggesting that the transcription factor Sp1 plays a
      role. Sp1 bound multiple Sp1 sites on the TRAIL promoter, including two
      established (Sp1-1 and -2) and two novel Sp1-5/6 and -7 sites. PDGF-BB-inducible
      TRAIL promoter activity by Sp1 was mediated through these sites, since transverse
      mutations to each abolished inducible activity. PDGF-BB stimulation increased
      acetylation of histone-3 (ac-H3) and expression of the transcriptional co
      activator p300, implicating chromatin remodelling. p300 overexpression increased
      TRAIL promoter activity, which was blocked by dominant-negative Sp1. Furthermore,
      PDGF-BB treatment increased the physical interaction of Sp1, p300 and ac-H3,
      while chromatin immunoprecipitation studies revealed Sp1, p300 and ac-H3
      enrichment on the TRAIL promoter. Taken together, our studies demonstrate for the
      first time that PDGF-BB-induced TRAIL transcriptional activity requires the
      cooperation of Sp1, ac-H3 and p300, mediating increased expression of TRAIL which
      is important for VSMC proliferation and migration. Our findings have the
      promising potential for targeting TRAIL as a new therapeutic for vascular
      proliferative disorders.

PMID- 22415976
TI  - 3D nanofluidic channels shaped by electron-beam-induced etching.
AB  - In-plane nanofluidic channels with 3D topography are fabricated. Nanochannel
      masters are written by electron beam lithography in SU-8 resist and shaped by
      electron-beam-induced etching (EBIE) with water as the precursor gas. Nanofunnel
      replicas cast from unmodified and EBIE-modified masters show that the funnel tip
      dimensions decrease from a 150-nm depth and 80-nm width to a 70-nm depth and 40
      nm width.

PMID- 22415977
TI  - Functionally convergent white adipogenic progenitors of different lineages
      participate in a diffused system supporting tissue regeneration.
AB  - Pathologies characterized by lipomatous infiltration of craniofacial structures
      as well as certain forms of lipodystrophies suggest the existence of a distinct
      adipogenic program in the cephalic region of mammals. Using lineage tracing, we
      studied the origin of craniofacial adipocytes that accumulate both in cranial fat
      depots and during ectopic lipomatous infiltration of craniofacial muscles. We
      found that unlike their counterparts in limb muscle, a significant percentage of
      cranial adipocytes is derived from the neural crest (NC). In addition, we
      identified a population of NC-derived Lin(-)/alpha7(-)/CD34(+)/Sca-1(+)
      fibro/adipogenic progenitors (NC-FAPs) that resides exclusively in the mesenchyme
      of cephalic fat and muscle. Comparative analysis of the adipogenic potential,
      impact on metabolism, and contribution to the regenerative response of NC-FAPs
      and mesoderm-derived FAPs (M-FAPs) suggests that these cells are functionally
      indistinguishable. While both NC- and M-FAPs express mesenchymal markers and
      promyogenic cytokines upon damage-induced activation, NC-FAPs additionally
      express components of the NC developmental program. Furthermore, we show that
      craniofacial FAP composition changes with age, with young mice containing FAPs
      that are almost exclusively of NC origin, while NC-FAPs are progressively
      replaced by M-FAPs as mice age. Based on these results, we propose that in the
      adult, ontogenetically distinct FAPs form a diffused system reminiscent of the
      endothelium, which can originate from multiple developmental intermediates to
      seed all anatomical locations.

PMID- 22415978
TI  - Vocal cord dysfunction in adolescents.
AB  - RATIONALE FOR THE STUDY: Vocal cord dysfunction (VCD) often presents with
      dramatic and abrupt symptoms. To diagnose VCD, visualization by direct
      laryngoscopy is required and because patients are usually asymptomatic, a
      specific method to provoke VCD is needed. Approaches to predict VCD by
      alterations of the flow-volume loop have been investigated. METHODS: Adolescents
      with clinical suspicion of VCD were invited to participate. After an initial
      pulmonary function test (PFT), direct laryngoscopy was performed. This was
      followed by a methacholine challenge test (MCT); the methacholine dose causing a
      20% drop in forced expiratory volume after 1 sec (FEV(1) ) (PD(20) FEV(1) ) was
      calculated. Then a second laryngoscopy was conducted. PFT changes before and
      after MCT were compared with the data of 14 healthy controls (HCs). RESULTS:
      Thirty-five patients (8-19 years) were investigated. Three showed anatomical
      alterations. Of the remaining 32 patients, 14 had VCD and 18 had bronchial
      hyperresponsiveness (non-VCD). In 29 patients with a positive MCT, PD(20) FEV(1)
      methacholine was significantly lower in VCD compared with non-VCD (VCD 0.24 +/-
      0.4 mg, non-VCD 0.73 +/- 0.73 mg, P = 0.0006). A PD(20) FEV(1)  < 0.24 mg
      methacholine predicted VCD with a sensitivity of 85% and a specificity of 75%.
      VCD patients showed significantly lower PFT parameters after challenge; FEV(1) :
      VCD 58.5 +/- 20.1%, non-VCD 80.2 +/- 18.0%, and HCs 98.7 +/- 16.6% (P < 0.0001).
      CONCLUSIONS: The combination of MCT and laryngoscopy may be able to differentiate
      between VCD and non-VCD. VCD patients showed a positive reaction at lower
      methacholine doses and displayed greater airway obstruction after MCT. PFTs and
      MCT do not replace direct laryngoscopy in the diagnosis of VCD in adolescents.

PMID- 22415979
TI  - Regio- and stereocontrolled introduction of secondary alkyl groups to electron
      deficient arenes through copper-catalyzed allylic alkylation.

PMID- 22415980
TI  - A restricted mixture model for dietary pattern analysis in small samples.
AB  - Multivariate finite mixture models have been applied to the identification of
      dietary patterns. These models are known to have many parameters, and
      consequently large samples are usually required. We present a special case of a
      multivariate mixture model that reduces the number of parameters to be estimated
      and seems adequate for small to moderately sized samples. We illustrate our
      approach with an analysis of Portuguese data from a food-frequency questionnaire
      and with a simulation study.

PMID- 22415981
TI  - Substituent electrophilicities in the NMR spectra of barbituric derivatives.
AB  - Comparison of the (1) H and (13)  C NMR spectra of a series of substituted 5
      benzylidene-N,N'-dimethylbarbituric acids (1) revealed chemical-shift variations
      of different centers that correlated with the theoretical electrophilicities or
      with the substituent electrophilic constant sigma(omega) , in an example of the
      usefulness of these DFT-based indices.

PMID- 22415982
TI  - A POSS-based supramolecular amphiphile and its hierarchical self-assembly
      behaviors.
AB  - A polyhedral oligomeric silsesquioxane (POSS)-based supramolecular amphiphile is
      prepared from the host-guest inclusion complexation between a mono adamantane
      functionalized POSS (AD-POSS) and a beta-cyclodextrin oligomer (P(beta-CD)).
      Assisted by the interface of H(2)O/toluene, the obtained supramolecular hybrids
      self-assemble into stable hollow nanospheres with thick walls. These hollow
      nanospheres aggregate together into a sphere layer through a spin coating
      technique, which then further transforms into a thin porous film containing
      nanometer-scale holes. The hollow nanospheres have a low cytotoxicity. The in
      vitro cell culture indicates the nanoporous films promote adhesion and
      proliferation of cells. The self-assembly morphologies and structures have been
      carefully characterized by SEM, TEM, AFM, DLS, XPS and water-contact angle
      measurements, and the self-assembly mechanism has also been discussed.

PMID- 22415983
TI  - Synthesis of a hierarchical three-component nanocomposite structure system with
      enhanced electrocatalytic and photoelectrical properties.
AB  - Effective control over the morphology and size of Pd/Pt nanoparticles is
      currently of immense interest because their electronic, optical, and catalytic
      properties are superior to pure platinum nanoparticles. However, control over the
      nanoparticle shape is still challenging. Therefore, a novel design and synthetic
      route needs to be developed to obtain a high-performance catalyst. Herein, a
      hierarchical three-component nanocomposite structure system (HTNSS) composed of
      graphene, TiO(2), and Pd@Pt core-shell nanoparticles was designed and synthesized
      by a sequential strategy that focuses on constructing the monolithic structure
      rather than limited single-component counterparts. The resulting composites were
      characterized by various techniques, which showed that the Pd@Pt core-shell
      nanoparticles were preferentially deposited on the peripheral interface of the
      graphene and TiO(2) nanoparticles. The photoelectrical and catalytic performances
      were obviously improved relative to the commercially available E-TEK Pt/C owing
      to their synergistic effect.

PMID- 22415984
TI  - Fano resonance in (gold core)-(dielectric shell) nanostructures without symmetry
      breaking.
AB  - A Fano resonance is observed in highly symmetric nanostructures comprising Au
      nanosphere cores and dielectric shells. It arises from the interference between
      the narrow plasmon resonance of the Au nanosphere core and the broad scattering
      background of the dielectric shell. The Fano resonance behavior is dependent on
      the gap distance between the core and shell and the shell material.

PMID- 22415986
TI  - Passage of health bill into law is unlikely to help GPs "heaving under the
      pressure" of NHS changes.

PMID- 22415987
TI  - Derivation of mesenchymal stem cells from human induced pluripotent stem cells
      cultured on synthetic substrates.
AB  - Human-induced pluripotent stem cells (hiPSCs) may represent an ideal cell source
      for research and applications in regenerative medicine. However, standard culture
      conditions that depend on the use of undefined substrates and xenogeneic medium
      components represent a significant obstacle to clinical translation. Recently, we
      reported a defined culture system for human embryonic stem cells using a
      synthetic polymer coating, poly[2-(methacryloyloxy)ethyl dimethyl-(3
      sulfopropyl)ammonium hydroxide] (PMEDSAH), in conjunction with xenogeneic-free
      culture medium. Here, we tested the hypothesis that iPSCs could be maintained in
      an undifferentiated state in this xeno-free culture system and subsequently be
      differentiated into mesenchymal stem cells (iPS-MSCs). hiPSCs were cultured on
      PMEDSAH and differentiated into functional MSCs, as confirmed by expression of
      characteristic MSC markers (CD166+, CD105+, CD90+,CD73+, CD31-, CD34-, and CD45-)
      and their ability to differentiate in vitro into adipogenic, chondrogenic, and
      osteoblastic lineages. To demonstrate the potential of iPS-MSCs to regenerate
      bone in vivo, the newly derived cells were induced to osteoblast differentiation
      for 4 days and transplanted into calvaria defects in immunocompromised mice for 8
      weeks. MicroCT and histologic analyses demonstrated de novo bone formation in the
      calvaria defects for animals treated with iPS-MSCs but not for the control group.
      Moreover, positive staining for human nuclear antigen and human mitochondria
      monoclonal antibodies confirmed the participation of the transplanted hiPS-MSCs
      in the regenerated bone. These results demonstrate that hiPSCs cultured in a xeno
      free system have the capability to differentiate into functional MSCs with the
      ability to form bone in vivo.

PMID- 22415988
TI  - Catalytic asymmetric hydrogenation of naphthalenes.

PMID- 22416005
TI  - Surgical management of pulmonary artery sling: trachea diameter and outcomes with
      or without tracheoplasty.
AB  - OBJECTIVES: Pulmonary artery sling is frequently associated with tracheal and/or
      bronchial stenosis. A number of patients receive only re-implantation or
      relocation of the left pulmonary artery (LPA) while other patients may require
      tracheoplasty for stenosis of the airway. This study used computer tomography
      (CT) scans for the evaluation of airways and to evaluate the trachea diameter and
      the clinical outcomes with or without tracheoplasty. METHODS: A total of 15
      patients with PA sling who received CT scans were included in this study. We
      reviewed the clinical outcomes and the severity of trachea stenosis, and
      evaluated various surgical strategies. RESULTS: Among the 15 patients, one
      received only conservative treatment, 14 (93%) patients received LPA re
      implantation, and eight (53%) received tracheoplasty. For the eight patients that
      received LPA reimplantation and tracheoplasty, five received slide tracheoplasty
      and all survived, two patients had pericardial patch augmentation and both died,
      and one patient received a resection and end-to-end anastomosis and survived. The
      diameter of the trachea in survivors without tracheoplasty was significantly
      larger than those who died or received tracheoplasty (3.2 +/- 0.3 mm vs. 2.2 +/-
      0.4 mm, P = 0.003). Establishing 3.0 mm as the threshold, the positive predictive
      value for tracheoplasty or mortality was 89% and the negative predictive value
      was 83%. CONCLUSIONS: In this study cohort, approximately 60% of the patients
      with PA sling received tracheoplasty. A diameter of the trachea <3 mm is
      associated with the use of tracheoplasty or poor outcomes. Slide tracheoplasty
      provided acceptable good results.

PMID- 22416006
TI  - Small-conductance calcium-activated K(+) channels 3 (SK3) regulate blastocyst
      hatching by control of intracellular calcium concentration.
AB  - BACKGROUND: The present study was designed to investigate the expression of small
      conductance calcium-activated K(+) channels 3 (SK3) in preimplantation embryos
      and to explore their role in the underlying mechanism of blastocyst hatching.
      METHODS: Human preimplantation embryos were donated by patients who achieved
      successful pregnancy with in vitro fertilization. Mouse preimplantation embryos
      in different stages were collected and cultured with or without siRNA cell
      injection. The expression of SK3 was examined by RT-PCR, quantitative real-time
      PCR, western blot and immunofluorescence. Functional expression of SK3 was
      investigated using the patch-clamp technique. [Ca(2+)]i was measured by
      fluorescent imaging. Embryos were cultured in vitro to investigate the effect of
      SK3 knockdown or apamin, an SK3 inhibitor, on blastocyst hatching and F-actin
      formation. RESULTS: In human blastocysts, the level of SK3 expression was
      significantly lower in blastocysts that failed to hatch than in blastocysts that
      hatched successfully. In mouse embryos, SK3 mRNA and protein were not found in
      zygotes, but were detected from the 2-cell stage onward, with the highest levels
      observed in blastocysts. SK3 was predominately located in the trophectoderm cell
      membrane of expanded blastocysts. SK3 knockdown in trophectoderm cells not only
      suppressed the SK3 current, but also reduced [Ca(2+)]i elevation and membrane
      potential hyperpolarization induced by thapsigargin. Although the formation of
      expanded blastocysts was not affected, blastocyst hatching and F-actin formation
      were significantly inhibited after SK3 knockdown in trophectoderm cells.
      CONCLUSIONS: SK3-mediated [Ca(2+)]i elevation and membrane potential
      hyperpolarization in trophectoderm cells are important for blastocyst hatching,
      and defects in SK3 expression may contribute to infertility.

PMID- 22416007
TI  - Segmental bowel resection for colorectal endometriosis: is there a correlation
      between histological pattern and clinical outcomes?
AB  - BACKGROUND: Laparoscopic segmental resection as a treatment for intestinal
      endometriosis can be supported by favorable clinical outcomes, but carries a high
      risk of major complications. The purpose of this study is to evaluate
      histopathological patterns of colorectal endometriosis and investigate potential
      relationships between histological findings and clinical data. METHODS: We
      consecutively included 47 patients treated with laparoscopic segmental resection
      because of symptomatic colorectal endometriosis. All patients underwent follow-up
      for a median of 18 months (range: 6-35). We examined the histological patterns of
      colorectal endometriosis and evaluated the relationships between histological
      findings (satellite lesions, positive margins and vertical infiltration) and
      clinical outcomes (incidence of recurrence, quality of life and symptom
      improvement). Moreover, we observed if satellite lesions could influence
      preoperative scores of the short form-36 health survey (SF-36) questionnaire and
      visual analogue score (VAS) for pain symptoms. RESULTS: There were no
      statistically significant differences in terms of anatomical and pain
      recurrences, pain symptoms and quality of life improvement among patients with or
      without positive margins, satellite lesions and different degrees of vertical
      infiltration (P > 0.05). Furthermore, women with or without satellite lesions
      were no different in terms of preoperative VAS of pain symptoms and SF-36 scores
      (P > 0.05). CONCLUSIONS: The presence of satellite lesions or positive resection
      margins does not seem to influence clinical outcomes of segmental colorectal
      resection. Similarly, satellite lesions do not appear to have a major role in
      determining preoperative clinical presentation. These results may be useful to
      reconsider the surgical strategy for bowel endometriosis.

PMID- 22416008
TI  - Estimation of the frequency of involuntary infertility on a nation-wide basis.
AB  - BACKGROUND: Assessing couple fecundity on a nation-wide basis without excluding
      couples who eventually remain infertile is challenging. Our aim was to describe
      couple fecundity (in terms of frequency of involuntary infertility) among the
      general population living in France. METHODS: We used a current-duration design.
      A random sample of 64 262 households was selected in 2007-2008, allowing us to
      identify 15 810 women aged 18-44 years. Eligible women (n= 1089) were those
      having regular sexual intercourse with a male partner, not using any method of
      contraception and not having delivered in the previous 3 months. These women
      reported information on the current duration of unprotected intercourse (CDUI,
      the time elapsed between the start of the period of unprotected intercourse and
      the time of inclusion in the study). The CDUI distribution was used to estimate
      the frequency of involuntary infertility, using a newly developed statistical
      technique that does not require couples to be followed up until the end of the
      period of unprotected intercourse. RESULTS: CDUI was defined for 867 women. An
      estimated 46% of couples had no detected pregnancy conceived during the first 6
      months of unprotected intercourse [95% confidence interval (CI), 36-56%]. The
      proportions of couples with no detected pregnancy within 12 and 24 months were
      24% (19-30%) and 11% (8-14%), respectively. CONCLUSIONS: These results constitute
      one of the few descriptions of the fecundity of a nation-wide representative
      sample of couples from the general population, not limited to couples who
      eventually conceived or to those resorting to medical help.

PMID- 22416009
TI  - Endothelial dysfunction but not increased carotid intima-media thickness in young
      European women with endometriosis.
AB  - BACKGROUND: Atherosclerosis is a chronic and degenerative disease developing
      typically in the elderly; nonetheless, a condition of accelerated atherosclerosis
      can be observed precociously in the presence of some diseases. Endometriosis, a
      chronic benign gynecological disorder, shows some characteristics, such as
      oxidative stress, systemic inflammation and a pro-atherogenic lipid profile,
      which could increase the risk of developing accelerated atherosclerosis. The aim
      of our study was to evaluate markers of subclinical atherosclerosis in young
      European women with endometriosis. METHODS: This cross-sectional study included
      37 women with endometriosis and 31 control subjects. The presence of subclinical
      atherosclerosis was investigated by ultrasound evaluation of common carotid
      intima-media thickness (ccIMT) and flow-mediated dilation (FMD); in addition,
      serum levels of lipids, inflammatory and coagulation parameters, as well as
      markers of endothelial inflammation and activation, were determined. RESULTS:
      Women with endometriosis showed significantly lower values of FMD compared with
      controls [mean difference: -4.62, 95% confidence interval (CI): -6.52, -2.73; P <
      0.001], whereas no significant differences in ccIMT values were found between the
      two groups. As regards markers of endothelial inflammation and activation, women
      with endometriosis had significantly higher values of inter-cellular adhesion
      molecule 1 (P < 0.001), vascular cell adhesion molecule 1 (P < 0.001), E-selectin
      (P < 0.001), von Willebrand factor (P = 0.004) and ristocetin cofactor (P =
      0.001) compared with controls. CONCLUSIONS: Our study suggests that women with
      endometriosis have more subclinical atherosclerosis, resulting in a higher risk
      of developing cardiovascular disorders. Moreover, our findings demonstrate that
      endothelial dysfunction can occur in the absence of structural atherosclerotic
      changes; its evaluation might be helpful in young women with endometriosis.

PMID- 22416010
TI  - Diagnostic value of serum activin A and follistatin levels in women with
      peritoneal, ovarian and deep infiltrating endometriosis.
AB  - BACKGROUND: Activin A is a growth factor, produced by the endometrium, whose
      actions are modulated by the binding protein follistatin. Both proteins are
      detectable in the peripheral serum and their concentrations may be increased in
      women with endometriosis. The present study was designed to evaluate whether
      serum levels of activin A and follistatin are altered, and therefore have a
      potential diagnostic value, in women with peritoneal, ovarian and deep
      infiltrating endometriosis. METHODS: We performed a multicenter controlled study
      evaluating simultaneously serum activin A and follistatin concentrations in women
      with and without endometriosis. Women with endometriosis (n = 139) were
      subdivided into three groups: peritoneal endometriosis (n = 28); ovarian
      endometrioma (n = 61) and deep infiltrating endometriosis (n = 50). The control
      group (n = 75) consisted of healthy women with regular menstrual cycles. Blood
      samples were collected from a peripheral vein and assayed for activin A and
      follistatin using commercially available enzyme immunoassay kits. RESULTS: The
      ovarian endometrioma group had serum activin A levels significantly higher than
      healthy controls (0.22 +/- 0.01 ng/ml versus 0.17 +/- 0.01 ng/ml, P < 0.01). None
      of the endometriosis groups had serum follistatin levels which were significantly
      altered compared with healthy controls; however, levels found in the endometrioma
      group (2.34 +/- 0.32 ng/ml) were higher than that in the deep endometriosis group
      (1.50 +/- 0.17 ng/ml, P < 0.05). The area under the receiver operating
      characteristic curve of activin A was 0.700 (95% confidence interval: 0.605
      0.794), while that of follistatin was 0.620 (95% confidence interval: 0.510
      0.730) for the diagnosis of ovarian endometrioma. The combination of both markers
      into a duo marker index did not improve significantly their diagnostic accuracy.
      CONCLUSIONS: The present study demonstrated that serum activin A and follistatin
      are not significantly altered in peritoneal or deep infiltrating endometriosis
      and have limited diagnostic accuracy in the diagnosis of ovarian endometrioma.

PMID- 22416011
TI  - Fertile offspring derived from mouse spermatogonial stem cells cryopreserved for
      more than 14 years.
AB  - BACKGROUND: Approximately 80% of childhood cancers can now be cured but a side
      effect of treatment results in about one-third of the surviving boys being
      infertile or severely subfertile when they reach reproductive age. Currently,
      more than 1 in 5000 men of reproductive age who are childhood cancer survivors
      suffer from this serious quality of life problem. It is possible to obtain a
      testicular biopsy before treatment to preserve the spermatogonial stem cells
      (SSCs) of the male by cryopreservation, but the results of long-term storage of
      SSCs on their subsequent functional ability to generate normal offspring has not
      been examined in any mammalian species. Moreover, it will be necessary to
      increase the number of these cryopreserved SSCs to remove any contaminating
      malignant cells and assure regeneration of spermatogenesis. METHODS AND RESULTS:
      In this report, we demonstrate that long-term cryopreservation (>14 years) of
      testis cells from mouse, rat, rabbit and baboon safeguards SSC viability, and
      that these cells can colonize the seminiferous tubules of recipient testes.
      Moreover, mouse and rat SSCs can be cultured and re-establish complete
      spermatogenesis, and fertile mouse progeny without apparent genetic or epigenetic
      errors were generated by the sperm produced. CONCLUSIONS: These findings provide
      a platform for fertility preservation in prepubertal boys undergoing gonadotoxic
      treatments.

PMID- 22416012
TI  - SEMA3A deletion in a family with Kallmann syndrome validates the role of
      semaphorin 3A in human puberty and olfactory system development.
AB  - BACKGROUND: Kallmann syndrome (KS) is a genetic disorder associating pubertal
      failure with congenitally absent or impaired sense of smell. KS is related to
      defective neuronal development affecting both the migration of olfactory nerve
      endings and GnRH neurons. The discovery of several genetic mutations responsible
      for KS led to the identification of signaling pathways involved in these
      processes, but the mutations so far identified account for only 30% of cases of
      KS. Here, we attempted to identify new genes responsible for KS by using a pan
      genomic approach. METHODS: From a cohort of 120 KS patients, we selected 48
      propositi with no mutations in known KS genes. They were analyzed by comparative
      genomic hybridization array, using Agilent 105K oligonucleotide chips with a mean
      resolution of 50 kb. RESULTS: One propositus was found to have a heterozygous
      deletion of 213 kb at locus 7q21.11, confirmed by real-time qPCR, deleting 11 of
      the 17 SEMA3A exons. This deletion cosegregated in the propositus' family with
      the KS phenotype, that was transmitted in autosomal dominant fashion and was not
      associated with other neurological or non-neurological clinical disorders. SEMA3A
      codes for semaphorin 3A, a protein that interacts with neuropilins. Mice lacking
      semaphorin 3A expression have been showed to have a Kallmann-like phenotype.
      CONCLUSIONS: SEMA3A is therefore a new gene whose loss-of-function is involved in
      KS. These findings validate the specific role of semaphorin 3A in the development
      of the olfactory system and in neuronal control of puberty in humans.

PMID- 22416014
TI  - Multinuclear magnetic resonance studies of 2-aryl-1,3,4-selenadiazoles.
AB  - 2-Aryl-1,3,4-selenadiazoles were studied by (1) H, (13) C, (15) N and (77) Se NMR
      spectroscopy. The results (chemical shifts and coupling constants) were
      correlated with Hammett substituent parameters as well as calculated chemical
      shifts and bond lengths.

PMID- 22416013
TI  - Dietary fat and semen quality among men attending a fertility clinic.
AB  - BACKGROUND: The objective of this study was to examine the relation between
      dietary fats and semen quality parameters. METHODS: Data from 99 men with
      complete dietary and semen quality data were analyzed. Fatty acid levels in sperm
      and seminal plasma were measured using gas chromatography in a subgroup of men (n
      = 23). Linear regression was used to determine associations while adjusting for
      potential confounders. RESULTS: Men were primarily Caucasian (89%) with a mean
      (SD) age of 36.4 (5.3) years; 71% were overweight or obese; and 67% were never
      smokers. Higher total fat intake was negatively related to total sperm count and
      concentration. Men in the highest third of total fat intake had 43% (95%
      confidence interval (CI): 62-14%) lower total sperm count and 38% (95% CI: 58
      10%) lower sperm concentration than men in the lowest third (P(trend) = 0.01).
      This association was driven by intake of saturated fats. Levels of saturated
      fatty acids in sperm were also negatively related to sperm concentration (r= 
      0.53), but saturated fat intake was unrelated to sperm levels (r = 0.09). Higher
      intake of omega-3 polyunsaturated fats was related to a more favorable sperm
      morphology. Men in the highest third of omega-3 fatty acids had 1.9% (0.4-3.5%)
      higher normal morphology than men in the lowest third (P(trend) = 0.02).
      CONCLUSIONS: In this preliminary cross-sectional study, high intake of saturated
      fats was negatively related to sperm concentration whereas higher intake of omega
      3 fats was positively related to sperm morphology. Further, studies with larger
      samples are now required to confirm these findings.

PMID- 22416015
TI  - The use of novel biomarkers to determine dietary mercury accumulation in nestling
      waterbirds.
AB  - Mercury (Hg) depuration into growing feathers is a well-studied phenomenon in
      waterbirds. Although the kinetics of Hg excretion in relation to molt and diet
      has been studied extensively, the relationship between the individual nutritional
      condition of nestlings and dietary Hg accumulation has not been investigated. In
      the present study, a body-condition index (BCI) and nutritional condition index
      (NCI) for nestlings of two waterbird species occupying different trophic
      positions on the aquatic food web were determined and used to predict Hg
      accumulation through diet. Candidate models consisting of these indices and
      nestling age were compared using Akaike's information criterion corrected for
      small sample sizes. For both species, the top-performing model contained the sole
      parameter of nutritional condition index (NCI). The relationship between Hg and
      NCI was stronger in the species foraging higher on the trophic web, which
      experienced higher rates of Hg depuration into feathers. Models containing BCI
      could not be discounted (AICc < 2) for one of the species and the utility of this
      index is discussed.

PMID- 22416016
TI  - Oligonuclear molecular models of intermetallic phases: a case study on
      [Pd2Zn6Ga2(Cp*)5(CH3)3].
AB  - The synthesis, characterization, and theoretical investigation by means of
      quantum-chemical calculations of an oligonuclear metal-rich compound are
      presented. The reaction of homoleptic dinuclear palladium compound [Pd(2)(MU
      GaCp*)(3)(GaCp*)(2)] with ZnMe(2) resulted in the formation of unprecedented
      ternary Pd/Ga/Zn compound [Pd(2)Zn(6)Ga(2)(Cp*)(5)(CH(3))(3)] (1), which was
      analyzed by (1)H and (13)C NMR spectroscopy, MS, elemental analysis, and single
      crystal X-ray diffraction. Compound 1 consisted of two C(s)-symmetric molecular
      isomers, as revealed by NMR spectroscopy, at which distinct site-preferences
      related to the Ga and Zn positions were observed by quantum-chemical
      calculations. Structural characterization of compound 1 showed significantly
      different coordination environments for both palladium centers. Whilst one Pd
      atom sat in the central of a bi-capped trigonal prism, thereby resulting in a
      formal 18-valence electron fragment, {Pd(ZnMe)(2)(ZnCp*)(4)(GaMe)}, the other Pd
      atom occupied one capping unit, thereby resulting in a highly unsaturated 12
      valence electron fragment, {Pd(GaCp*)}. The bonding situation, as determined by
      atoms-in-molecules analysis (AIM), NBO partial charges, and molecular orbital
      (MO) analysis, pointed out that significant Pd-Pd interactions had a large stake
      in the stabilization of this unusual molecule. The characterization and quantum
      chemical calculations of compound 1 revealed distinct similarities to related
      M/Zn/Ga Hume-Rothery intermetallic solid-state compounds, such as Ga/Zn-exchange
      reactions, the site-preferences of the Zn/Ga positions, and direct M-M bonding,
      which contributes to the overall stability of the metal-rich compound.

PMID- 22416017
TI  - Hippocampal theta-driving cells revealed by Granger causality.
AB  - The two-dipole model of theta generation in hippocampal CA1 suggests that the
      inhibitory perisomatic theta dipole is generated by local GABAergic interneurons.
      Various CA1 interneurons fire preferentially at different theta phases, raising
      the question of how these theta-locked interneurons contribute to the generation
      of theta oscillations. We here recorded interneurons in the hippocampal CA1 area
      of freely behaving mice, and identified a unique subset of theta-locked
      interneurons by using the Granger causality approach. These cells fired in an
      extremely reliable theta-burst pattern at high firing rates (~90 Hz) during
      exploration and always locked to ascending phases of the theta waves. Among theta
      locked interneurons we recorded, only these cells generated strong Granger causal
      influences on local field potential (LFP) signals within the theta band (4-12
      Hz), and the influences were persistent across behavioral states. Our results
      suggest that this unique type of theta-locked interneurons serve as the local
      inhibitory theta dipole control cells in shaping hippocampal theta oscillations.

PMID- 22416018
TI  - Surface plasmon resonance biosensors incorporating gold nanoparticles.
AB  - SPR biosensing is increasingly popular for the detection of a multitude of
      biomolecules. It offers label-free detection and study of proteins, nucleic
      acids, and other biomolecules in real time. A recent trend involves incorporation
      of AuNPs, either within the sensing surface itself or as signal enhancing tagging
      molecules. The importance of AuNP and detecting agent spacing is described and
      techniques using macromolecular spacing aids are highlighted. Recent methods to
      enhance SPR detection capabilities using gold nanoparticles are reviewed, as well
      as device fabrication and the results of incorporation. SPR detection is a highly
      versatile method for the detection of biomolecules and, with the incorporation of
      AuNPs, shows promise in extending it to a number of new applications.

PMID- 22416019
TI  - Can mucosal healing be a cost-effective endpoint for biologic therapy in Crohn's
      disease? A decision analysis.
AB  - BACKGROUND: Observational studies have demonstrated that mucosal healing (MH) may
      be associated with reductions in hospitalizations and surgeries for moderate to
      severe Crohn's disease (CD). Whether treatment to achieve MH is a cost-effective
      endpoint has not been established previously. METHODS: We constructed a decision
      analytic model comparing two treatment strategies. In the clinical response (CR)
      arm, patients not in clinical remission at year 1 are dose-escalated. In the MH
      arm, patients with persistence of mucosal ulcerations at year 1 are escalated
      irrespective of clinical symptoms. Patients remain at risk for hospitalization
      and surgeries while they have active disease. We examined a 2-year time horizon.
      RESULTS: In the base case the MH strategy was more effective at 2 years (quality
      adjusted life year [QALY] 0.71) compared to the CR strategy (QALY 0.69) but was
      also more expensive with an incremental cost-effectiveness ratio (ICER) of
      $49,278/QALY gained. In a hypothetical cohort of 100,000 patients assigned to
      each treatment arm, the MH strategy resulted in lower rates of hospitalization
      and surgery with a number needed to treat of 27 and 106, respectively. The
      results were sensitive to the ability of infliximab to achieve MH and the
      incremental benefit of MH over clinical remission. CONCLUSIONS: We demonstrate
      that MH as an endpoint is a cost-effective strategy in CD patients initiating IFX
      therapy. Further prospective studies on durability of MH and its incremental
      benefit as well as the ability of other available biologic agents to achieve MH
      are necessary to validate our findings.

PMID- 22416020
TI  - UV radiation induces genome-mediated, site-specific cleavage in viral proteins.
AB  - Much research has been dedicated to understanding the molecular basis of UV
      damage to biomolecules, yet many questions remain regarding the specific pathways
      involved. Here we describe a genome-mediated mechanism that causes site-specific
      virus protein cleavage upon UV irradiation. Bacteriophage MS2 was disinfected
      with 254 nm UV, and protein damage was characterized with ESI- and MALDI-based FT
      ICR, Orbitrap, and TOF mass spectroscopy. Top-down mass spectrometry of the
      products identified the backbone cleavage site as Cys46-Ser47 in the virus capsid
      protein, a location of viral genome-protein interaction. The presence of viral
      RNA was essential to inducing backbone cleavage. The similar bacteriophage GA did
      not exhibit site-specific protein cleavage. Based on the major protein fragments
      identified by accurate mass analysis, a cleavage mechanism is proposed by radical
      formation. The mechanism involves initial oxidation of the Cys46 side chain
      followed by hydrogen atom abstraction from Ser47 C(alpha). Computational protein
      QM/MM studies confirmed the initial steps of the radical mechanism. Collectively,
      this study describes a rare incidence of genome-induced protein cleavage without
      the addition of sensitizers.

PMID- 22416021
TI  - Effectiveness of sequencing selected exons of DNAH5 and DNAI1 in diagnosis of
      primary ciliary dyskinesia.
AB  - INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare genetically heterogenous
      condition. Mutations in DNAH5 or DNAI1 genes can be found in about a third of the
      patients with PCD. Increased occurrence of mutations was described in several
      exons of these long genes. The objective of the study was to test the sensitivity
      of sequencing of selected 13 exons (as compared to costly sequencing of all 100
      exons of the two genes), and to determine the prevalence of the DNAH5 or DNAI1
      mutations in the Czech PCD database. METHODS: The Czech national PCD database has
      identified 31 pediatric patients, diagnosed based on clinical findings and tests
      on the ciliated epithelium. Twenty-seven patients from 24 families agreed on
      genetic testing. In the first step, direct sequencing of selected 13 exons (9 of
      DNAH5 and 4 of DNAI1) was performed, and then we compared its effectiveness in
      detecting at least one mutation with results of sequencing all 100 exons of the
      two genes. RESULTS: The sequencing of all exons identified compound
      heterozygosity for PCD mutations in nine patients from eight families (DNAH5 in
      eight and DNAI1 in one patient), and heterozygozity for a DNAH5 mutation of
      uncertain functional significance in one additional patient. The first step of
      selected exon sequencing detected a mutation in five out of these eight families,
      its actual sensitivity being 62.5%, with a high predictive value. The phenotypic
      and clinical characteristics of all the paediatric patients with PCD are shown.
      CONCLUSIONS: Selected exon sequencing detects at least one mutated allele in over
      a half of our patients who have PCD due to DNAH5 or DNAI1 mutations. To lower the
      costs of the genetic testing, targeted step-wise genetic testing may be a
      reasonable approach to detect mutations in PCD patients, especially if their
      phenotype is taken into account.

PMID- 22416022
TI  - Structure elucidation and NMR assignments of an unusual triterpene saponin
      derivative from Ilex kudincha.
AB  - One unusual triterpenoid derivative, ilekudinchoside E (1), was isolated from the
      leaves of Ilex kudincha. The structure was established by various spectroscopic
      techniques, including one- and two-dimensional NMR, HRTOFMS and CD spectra.

PMID- 22416023
TI  - Construction of a microstructured collagen membrane mimicking the papillary
      dermis architecture and guiding keratinocyte morphology and gene expression.
AB  - A papillary-structured collagen fibril membrane is created, mimicking the 3D
      architecture of the human papillary dermis. Primary human keratinocytes cultured
      to confluency on papillar-structured films are compared to keratinocytes cultured
      on flat membranes. Microscopical evaluation reveals the presence of
      morphologically distinct cells at the base of the papillar structures that are
      not observed on flat membranes. Gene expression microarrays and RT-qPCR indicate
      that these cells are in a more proliferative/migrational state, whereas cells on
      flat membranes have a more differentiated expression profile. Immunohistochemical
      stainings confirm these results. In conclusion, specific collagen architecture
      can direct keratinocyte behavior, and this may be used to further improve skin
      regeneration.

PMID- 22416024
TI  - Geometric and electronic structures of phenoxyl radicals hydrogen bonded to
      neutral and cationic partners.
AB  - Two di-tert-butylphenols incorporating an N-methylbenzimidazole moiety in the
      ortho or para position have been synthesised ((Me)OH and (pMe)OH, respectively).
      Their X-ray structures evidence a hydrogen bond between the phenolic proton and
      the iminic nitrogen atom, whose nature is intra- and intermolecular,
      respectively. The present studies demonstrate that (Me)OH is readily oxidised by
      an intramolecular PET mechanism to form the hydrogen-bonded phenoxyl-N
      methylbenzimidazolium system ((Me)OH)(.+) , whereas oxidation of (pMe)OH occurs
      by intermolecular PET, affording the neutral phenoxyl benzimidazole ((pMe)O)(.)
      system. The deprotonations of (Me)OH and (pMe)OH yield the corresponding
      phenolate species ((Me)O)(-) and ((pMe)O)(-), respectively, whilst that of the
      previously reported (H)OH (analogous to (Me)OH but lacking the N-methyl group)
      produces an unprecedented hydrogen-bonded phenol benzimidazolate species, as
      evidenced by its X-ray structure. The latter is believed to be in equilibrium in
      solution with its tautomeric phenolate form, as suggested by NMR,
      electrochemistry and DFT studies. The one-electron oxidations of the anions occur
      by a simple ET process affording phenoxyl radical species, whose electronic
      structure has been studied by HF-EPR spectroscopy and DFT calculations. In
      particular, analysis of the g(1) tensor shows the order
      2.0079>2.0072>2.0069>2.0067 for ((Me)O)(.), ((H)O)(.), ((Me)OH)(.+) and
      ((H)OH)(.+), respectively. ((Me)O)(.) exhibits the largest g(1) tensor (2.0079),
      consistent with the absence of intramolecular hydrogen bond. The g(1) tensor of
      ((H)O)(.) is intermediate between those of ((Me)OH)(.+) and ((Me)O)(.)
      (g(1)=2.0072), indicating that the phenoxyl oxygen is hydrogen-bonded with a
      neutral benzimidazole partner.

PMID- 22416025
TI  - Growing pains: twin family study evidence for genetic susceptibility and a
      genetic relationship with restless legs syndrome.
AB  - BACKGROUND: Growing pains (GP) is a prevalent familial childhood disorder of
      unknown aetiology. Familial occurrence of GP, and individual and familial
      association of GP with restless legs syndrome (RLS) has been reported. METHODS:
      We applied a twin family design to search for evidence of genetic susceptibility
      to GP, and for a genetic relationship between GP and RLS. The parents of 1843
      twin pairs aged 3-16 years were administered a questionnaire, which identified 88
      pairs with at least one twin individual fulfilling criteria for GP. Standard
      questionnaires for history of GP and RLS were completed for these twin pairs,
      their siblings and parents. RESULTS: Twenty-five of 34 monozygotic (MZ) pairs
      were concordant for GP, compared with 12 of the 54 dizygotic (DZ) pairs. The
      casewise concordance was 0.85 and 0.36 for MZ and DZ pairs, respectively (p <
      0.001). The lifetime GP prevalence for relatives of twins with GP was 51% for non
      twin siblings, 47% for parents. Twenty-three percent of twin individuals with GP
      met RLS criteria compared with 8% of twin individuals without GP (p = 0.03). Of
      the twins with GP concordance, 19% met RLS criteria compared with 2% of twins
      with GP discordance (p = 0.01). In two MZ pairs, one had GP and the other RLS.
      The lifetime prevalence of RLS was 40% for mothers, and 24% for fathers and 18%
      for non-twin siblings. CONCLUSION: This first twin family study of GP provides
      evidence for a genetic aetiology and for a genetic relationship to RLS.

PMID- 22416027
TI  - Benchmark calculations of (29) Si-(1) H spin-spin coupling constants across
      double bond.
AB  - Benchmark calculations of geminal and vicinal (29) Si-(1) H spin-spin coupling
      constants across double bond in three reference alkenylsilanes have been carried
      out at both DFT and SOPPA levels in comparison with experiment. At the former,
      four density functionals, B3LYP, B3PW91, PBE0 and KT3, were tested in combination
      with five representative basis sets. At the latter, three main SOPPA-based
      methods, SOPPA, SOPPA(CC2) and SOPPA(CCSD), were examined in combination with the
      same series of basis sets. On the whole, the wavefunction methods showed much
      better results as compared to DFT, with the most efficient combination of
      SOPPA/cc-pVTZ-su2 characterized by a mean absolute error of only 0.4 Hz
      calculated for a set of nine coupling constants in three compounds with a sample
      span of around 40 Hz.

PMID- 22416028
TI  - Kinetic and stoichiometric characterisation of streptavidin-binding aptamers.
AB  - Aptamers are oligonucleotide ligands that are selected for high-affinity binding
      to molecular targets. Only limited knowledge relating to relations between
      structural and kinetic properties that define aptamer-target interactions is
      available. To this end, streptavidin-binding aptamers were isolated and
      characterised by distinct analytical techniques. Binding kinetics of five broadly
      similar aptamers were determined by surface plasmon resonance (SPR); affinities
      ranged from 35-375 nM with large differences in association and dissociation
      rates. Native mass spectrometry showed that streptavidin can accommodate up to
      two aptamer units. In a 3D model of one aptamer, conserved regions are exposed,
      strongly suggesting that they directly interact with the biotin-binding pockets
      of streptavidin. Mutational studies confirmed both conserved regions to be
      crucial for binding. An important result is the observation that the most
      abundant aptamer in our selections is not the tightest binder, emphasising the
      importance of having insight into the kinetics of complex formation. To find the
      tightest binder it might be better to perform fewer selection rounds and to focus
      on post-selection characterisation, through the use of complementary approaches
      as described in this study.

PMID- 22416029
TI  - Branched mesoporous Mn3O4 nanorods: facile synthesis and catalysis in the
      degradation of methylene blue.
AB  - Branched MnOOH nanorods with diameters in the range of 50-150 nm and lengths of
      up to tens of micrometers were prepared by using potassium permanganate (KMnO(4))
      and PEG 400 (PEG=polyethylene glycol) as starting materials through a simple
      hydrothermal process at 160  degrees C. After annealing at 300  degrees C under a
      N(2) atmosphere for 5 h, MnOOH nanorods became gradually dehydrated and
      transformed into mesoporous Mn(3)O(4) nanorods with a slight size-shrinking. The
      as-obtained mesoporous Mn(3)O(4) nanorods had an average surface area of 32.88
      m(2) g(-1) and a mean pore size of 3.7 nm. Through tuning the experimental
      parameters, such as the annealing atmosphere and temperature, beta-MnO(2),
      Mn(2)O(3), Mn(3)O(4), MnO, and Mn(5)O(8) were selectively produced. Among these
      structures, mesoporous Mn(3)O(4) nanorods were efficient for the catalytic
      degradation of methylene blue (MB) in the presence of H(2)O(2) at 80  degrees C.

PMID- 22416030
TI  - Photo-crosslinked biodegradable hydrogels prepared from fumaric acid monoethyl
      ester-functionalized oligomers for protein delivery.
AB  - Photo-crosslinkable, fumaric acid monoethyl ester-functionalized triblock
      oligomers are synthesized and copolymerized with N-vinyl-2-pyrrolidone to form
      biodegradable photo-crosslinked hydrogels. Poly(ethylene glycol) is used as the
      middle hydrophilic segment and the hydrophobic segments are based on D,L-lactide,
      trimethylene carbonate or a mixture of these monomers. Two model proteins,
      lysozyme and albumin, are incorporated in the hydrogels and their release is
      studied. The composition of the hydrophobic segments could be used to tune
      degradation behavior and release rates. Careful optimization of photo
      polymerization conditions is needed to limit conjugation of proteins to the
      hydrogels and protein denaturation.

PMID- 22416031
TI  - Genetic variation in the beta-2 adrenergic receptor is associated with chronic
      musculoskeletal complaints in adolescents.
AB  - BACKGROUND: There is significant evidence to suggest that psychological and
      stress-related factors are important predictors of the onset of chronic
      widespread pain (CWP) and fibromyalgia (FM). The hypothalamic-pituitary-adrenal
      axis, together with the efferent sympathetic/adrenomedullary system, influence
      all body organs (including muscles) during short- and long-term threatening
      stimuli. The aim of this study was to investigate the relationship between
      genetic variants in adrenergic candidate genes and chronic musculoskeletal
      complaints (MSCs) in adolescents. METHODS: Adolescents from the Western
      Australian Pregnancy (Raine) Cohort attending the 17-year cohort review completed
      a questionnaire containing a broad range of psychosocial factors and pain
      assessment (n = 1004). Blood samples were collected for DNA extraction and
      genotyping. Genotype data was obtained for 14 single nucleotide polymorphisms
      (SNPs) in two candidate genes - beta-2 adrenergic receptor (ADRB2) and
      catecholamine-O-methyltransferase (COMT). Haplotypes were reconstructed for all
      individuals with genotype data. RESULTS AND CONCLUSION: Both female gender and
      poor mental health were associated with (1) an increased risk for chronic,
      disabling comorbid neck and low back pain (CDCP); and (2) an increase in the
      number of areas of pain. Of the 14 SNPs evaluated, only SNP rs2053044 (ADRB2,
      recessive model) displayed an association with CDCP [odds ratio (OR) = 2.49; 95%
      confidence interval (CI) = 1.25, 4.98; p = 0.01] and pain in three to four pain
      areas in the last month (OR = 1.86; 95% CI = 1.13, 3.06; p = 0.02). These data
      suggest that genetic variants in ADRB2 may be involved in chronic MSCs.

PMID- 22416032
TI  - Trends in treatment of newly treated schizophrenia-spectrum disorder patients in
      Taiwan from 1999 to 2006.
AB  - PURPOSE: This study aimed to examine trends in the first-year pharmacological
      treatment of newly treated schizophrenia patients in Taiwan between 1999 and
      2006. METHOD: We collected data from the National Health Insurance Research
      Database of all newly treated patients with a diagnosis of schizophrenia-spectrum
      disorder (ICD-9 295.x). We analyzed all prescription records after diagnosis of
      schizophrenia and described the patterns of antipsychotics use, other concomitant
      psychotropic agents use, and mental health system utilization. We tested for
      trend using multivariate logistic regression and Spearman's partial correlation
      rank test. RESULTS: A total of 2895 newly treated patients with schizophrenia
      were enrolled. The percentage of prescriptions of second-generation
      antipsychotics (SGAs) was found to have increased significantly, from 27.5% in
      1999 to 76.9% in 2006. The ratio of good antipsychotics adherence (medication
      possession ratio >0.8) also increased, from 23.2% in 1998 to 38.9% in 2006.
      Corresponding to this, the percentage of usage of first-generation antipsychotic
      drugs, anticholinergic agents, and long-term combination therapy declined.
      However, the prescription of antidepressants and mood stabilizers and the
      hospitalization rate increased. No change was noted in the number of psychiatric
      visits. CONCLUSION: In the first-year treatment of newly treated schizophrenic
      patients between 1999 and 2006, we found pharmacological treatment had changed in
      terms of types of antipsychotics, adherence, and the use of other concomitant
      psychotropic agents, with the introduction of SGAs. The benefits and costs of the
      changes with a trend toward an increasing prescription of SGAs warrant further
      investigation.

PMID- 22416033
TI  - Hearing aid for vertebrates via multiple episodic adaptive events on prestin
      genes.
AB  - Auditory detection is essential for survival and reproduction of vertebrates, yet
      the genetic changes underlying the evolution and diversity of hearing are poorly
      documented. Recent discoveries concerning prestin, which is responsible for
      cochlear amplification by electromotility, provide an opportunity to redress this
      situation. We identify prestin genes from the genomes of 14 vertebrates,
      including three fishes, one amphibian, one lizard, one bird, and eight mammals.
      An evolutionary analysis of these sequences and 34 previously known prestin genes
      reveals for the first time that this hearing gene was under positive selection in
      the most recent common ancestor (MRCA) of tetrapods. This discovery might
      document the genetic basis of enhanced high sound sensibility in tetrapods. An
      investigation of the adaptive gain and evolution of electromotility, an important
      evolutionary innovation for the highest hearing ability of mammals, detects
      evidence for positive selections on the MRCA of mammals, therians, and
      placentals, respectively. It is suggested that electromotility determined by
      prestin might initially appear in the MRCA of mammals, and its functional
      improvements might occur in the MRCA of therian and placental mammals. Our patch
      clamp experiments further support this hypothesis, revealing the functional
      divergence of voltage-dependent nonlinear capacitance of prestin from platypus,
      opossum, and gerbil. Moreover, structure-based cdocking analyses detect
      positively selected amino acids in the MRCA of placental mammals that are key
      residues in sulfate anion transport. This study provides new insights into the
      adaptation and functional diversity of hearing sensitivity in vertebrates by
      evolutionary and functional analysis of the hearing gene prestin.

PMID- 22416034
TI  - Structure determination of fexofenadine-alpha-cyclodextrin complex by
      quantitative 2D ROESY analysis and molecular mechanics studies.
AB  - Complexation of fexofenadine with alpha-cyclodextrin in aqueous medium was
      studied. The stoichiometry of the resulting inclusion complex was determined by
      (1) H NMR titration data. 2D ROESY data provided the evidence of formation of the
      complex by entry of the phenyl ring into the alpha-cyclodextrin cavity probably
      from wider opening. Determination of relative peak intensities of intermolecular
      cross-peaks for the most stable complexes obtained by molecular mechanics (MM2)
      studies and from 2D ROESY spectral data confirmed the presence of only one
      complex in solution that has been fully characterized.

PMID- 22416036
TI  - Transcranial direct current stimulation does neither modulate results of a
      quantitative sensory testing protocol nor ratings of suprathreshold heat stimuli
      in healthy volunteers.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) has been shown to
      effectively modulate cortical excitability. Several studies have suggested
      clinical efficacy in pain syndromes such as central neuropathic pain or
      fibromyalgia. However, little is known regarding tDCS effects on nociception in
      healthy volunteers. METHODS: In the present study, we examined the effects of
      anodal, cathodal and sham stimulation of the left primary motor cortex in 17
      healthy volunteers on modalities of a comprehensive quantitative sensory testing
      protocol (including thermal and mechanoreceptive detection and pain thresholds)
      and on a repetitive heat pain paradigm mimicking clinical pain. The study was
      conducted in a single-blind crossover fashion. tDCS was applied at 1 mA for 15
      min. RESULTS: We could not detect any relevant modulation of somatosensory and
      pain variables in quantitative sensory testing. In addition, no significant
      alteration of enhanced pain ratings to repetitive noxious heat stimuli (heat
      hyperalgesia) was found. CONCLUSION: As pain processing in chronic pain patients
      might differ, tDCS could exert its antinociceptive effects depending on the
      activation level of the nociceptive system.

PMID- 22416035
TI  - Enhanced cytotoxicity of PARP inhibition in mantle cell lymphoma harbouring
      mutations in both ATM and p53.
AB  - Poly-ADP ribose polymerase (PARP) inhibitors have shown promise in the treatment
      of human malignancies characterized by deficiencies in the DNA damage repair
      proteins BRCA1 and BRCA2 and preclinical studies have demonstrated the potential
      effectiveness of PARP inhibitors in targeting ataxia-telangiectasia mutated (ATM)
      deficient tumours. Here, we show that mantle cell lymphoma (MCL) cells deficient
      in both ATM and p53 are more sensitive to the PARP inhibitor olaparib than cells
      lacking ATM function alone. In ATM-deficient MCL cells, olaparib induced DNA-PK
      dependent phosphorylation and stabilization of p53 as well as expression of p53
      responsive cell cycle checkpoint regulators, and inhibition of DNA-PK reduced the
      toxicity of olaparib in ATM-deficient MCL cells. Thus, both DNA-PK and p53
      regulate the response of ATM-deficient MCL cells to olaparib. In addition, small
      molecule inhibition of both ATM and PARP was cytotoxic in normal human
      fibroblasts with disruption of p53, implying that the combination of ATM and PARP
      inhibitors may have utility in targeting p53-deficient malignancies.

PMID- 22416037
TI  - A flavoprotein monooxygenase that catalyses a Baeyer-Villiger reaction and
      thioether oxidation using NADH as the nicotinamide cofactor.
AB  - A gene from the marine bacterium Stenotrophomonas maltophilia encodes a 38.6 kDa
      FAD-containing flavoprotein (Uniprot B2FLR2) named S. maltophilia flavin
      containing monooxygenase (SMFMO), which catalyses the oxidation of thioethers and
      also the regioselective Baeyer-Villiger oxidation of the model substrate
      bicyclo[3.2.0]hept-2-en-6-one. The enzyme was unusual in its ability to employ
      either NADH or NADPH as nicotinamide cofactor. The K(M)  and k(cat)  values for
      NADH were 23.7+/-9.1 MUM and 0.029 s(-1)  and 27.3+/-5.3 MUM and 0.022 s(-1)  for
      NADPH. However, k(cat) /K(M)  value for the ketone substrate in the presence of
      100 MUM cofactor was 17 times greater for NADH than for NADPH. SMFMO catalysed
      the quantitative conversion of 5 mM ketone in the presence of substoichiometric
      concentrations of NADH with the formate dehydrogenase cofactor recycling system,
      to give the 2-oxa and 3-oxa lactone products of Baeyer-Villiger reaction in a
      ratio of 5:1, albeit with poor enantioselectivity. The conversion with NADPH was
      15 %. SMFMO also catalysed the NADH-dependent transformation of prochiral
      aromatic thioethers, giving in the best case, 80 % ee for the transformation of p
      chlorophenyl methyl sulfide to its R enantiomer. The structure of SMFMO reveals
      that the relaxation in cofactor specificity appears to be accomplished by the
      substitution of an arginine residue, responsible for recognition of the 2'
      phosphate on the NADPH ribose in related NADPH-dependent FMOs, with a glutamine
      residue in SMFMO. SMFMO is thus representative of a separate class of single
      component, flavoprotein monooxygenases that catalyse NADH-dependent oxidations
      from which possible sequences and strategies for developing NADH-dependent
      biocatalysts for asymmetric oxygenation reactions might be identified.

PMID- 22416038
TI  - Near-IR excitation transfer and electron transfer in a BF2-chelated
      dipyrromethane-azadipyrromethane dyad and triad.
AB  - A molecular dyad and triad, comprised of a known photosensitizer, BF(2)-chelated
      dipyrromethane (BDP), covalently linked to its structural analog and near-IR
      emitting sensitizer, BF(2)-chelated tetraarylazadipyrromethane (ADP), have been
      newly synthesized and the photoinduced energy and electron transfer were examined
      by femtosecond and nanosecond laser flash photolysis. The structural integrity of
      the newly synthesized compounds has been established by spectroscopic,
      electrochemical, and computational methods. The DFT calculations revealed a
      molecular-clip-type structure for the triad, in which the BDP and ADP entities
      are separated by about 14 A with a dihedral angle between the fluorophores of
      around 70 degrees . Differential pulse voltammetry studies have revealed the
      redox states, allowing estimation of the energies of the charge-separated states.
      Such calculations revealed a charge separation from the singlet excited BDP
      ((1)BDP*) to ADP (BDP(.+)-ADP(.-)) to be energetically favorable in nonpolar
      toluene and in polar benzonitrile. In addition, the excitation transfer from the
      singlet BDP to ADP is also envisioned due to good spectral overlap of the BDP
      emission and ADP absorption spectra. Femtosecond laser flash photolysis studies
      provided concrete evidence for the occurrence of energy transfer from (1)BDP* to
      ADP (in benzonitrile and toluene) and electron transfer from BDP to (1)ADP* (in
      benzonitrile, but not in toluene). The kinetic study of energy transfer was
      measured by monitoring the rise of the ADP emission and revealed fast energy
      transfer (ca. 10(11) s(-1)) in these molecular systems. The kinetics of electron
      transfer via (1)ADP*, measured by monitoring the decay of the singlet ADP at
      lambda=820 nm, revealed a relatively fast charge-separation process from BDP to
      (1)ADP*. These findings suggest the potential of the examined ADP-BDP molecules
      to be efficient photosynthetic antenna and reaction center models.

PMID- 22416039
TI  - Comfort First: an evaluation of a procedural pain management programme for
      children with cancer.
AB  - BACKGROUND: The Comfort First Program (CFP) provides children and their
      caregivers with early procedural pain management intervention to reduce
      procedural pain and distress. This study evaluated whether the CFP was meeting
      its goals and effectively implementing the Royal Australasian College of
      Physicians paediatric pain management guidelines. METHODS: The study was
      conducted as a single-site cross-sectional audit. One hundred and thirty-five
      patients (mean age 7.7 years) receiving treatment at the Royal Children's
      Hospital, Melbourne, Children's Cancer Centre Day Oncology Unit were observed.
      Procedural aspects related to the treatment room, carer and staff behaviour,
      child distress and use of pharmacologic and nonpharmacologic interventions were
      recorded using an audit tool developed for the study. RESULTS: The procedure room
      was regularly quiet and prepared before the child entered. Median procedure
      duration was 8 min. Median procedure wait time was 54 min. At least one carer was
      typically present during procedures. Comfort First (CF) clinicians were more
      likely to be present in procedures with a significantly distressed child. Carers,
      nurses and CF clinicians generally displayed comfort-promoting behaviour. Topical
      anaesthetic was regularly utilised. Nonpharmacologic supports were frequently
      used, particularly distraction. Patients under 8 years of age were significantly
      more likely to receive nonpharmacologic supports and have a carer and CF
      clinician present. Age was a significant predictor of distress, with higher
      distress rates in younger children. CONCLUSIONS: The CFP was found to be
      effectively implementing procedural pain guidelines. Regular audit is recommended
      to ensure adherence to pain management standards.

PMID- 22416041
TI  - Covalent functionalization of strained graphene.
AB  - An enhancement of the chemical activity of graphene is evidenced by first
      principles modelling of the chemisorption of hydrogen, fluorine, oxygen and
      hydroxyl groups on strained graphene. For the case of negative strain or
      compression, chemisorption of the single hydrogen, fluorine or hydroxyl group is
      energetically more favourable than those of their pairs on different sublattices.
      This behaviour stabilizes the magnetism caused by the chemisorption being against
      its destruction by the pair formations. Initially flat, compressed graphene is
      shown to buckle spontaneously right after chemisorption of single adatoms. Unlike
      hydrogenation or fluorination, the oxidation process turns from the endothermic
      to exothermic for all types of the strain and depends on the direction of applied
      strains. Such properties will be useful in designing graphene devices utilizing
      functionalization as well as mechanical strains.

PMID- 22416040
TI  - Pain-related catastrophizing in pain patients and people with pain in the general
      population.
AB  - BACKGROUND: Catastrophizing is a defining factor in the pain experience and
      strongly contributes to the prediction of various aspects of health.
      Catastrophizing is not just present in pain patients, but may also be present in
      people with non-clinical pain. The aim of the present study is to investigate
      levels of catastrophizing in pain patients and people with pain from the general
      population. Also, the relationship between catastrophizing and pain intensity,
      specialist consultation and use of pain medication is studied. METHODS: A cross
      sectional survey design was used, including 150 pain patients and 376 respondents
      from the general population. RESULTS: The results show that pain is highly
      prevalent in the general population. The pain patients reported significantly
      higher levels of pain intensity and catastrophizing than the community pain
      sample. In both samples, significant positive correlations between
      catastrophizing and pain intensity were found. The data show a linear
      relationship between catastrophizing and pain intensity, which can be interpreted
      as evidence for a dose-response pattern in pain-related catastrophizing.
      Furthermore, catastrophizing predicted specialist consultation and medication use
      in the community pain sample. CONCLUSIONS: It can be concluded that pain-related
      catastrophizing is present in pain patients as well as people with pain from the
      general population in a dose-response pattern. Catastrophizing seems to be an
      important factor determining certain aspects of pain-related medical consumption,
      even in non-clinical pain, and should therefore be a target of the screening
      procedure and early intervention.

PMID- 22416042
TI  - Amphiphilic Schiff base organogels: metal-ion-mediated chiral twists and chiral
      recognition.
AB  - New amphiphilic gelators that contained both Schiff base and L-glutamide
      moieties, abbreviated as o-SLG and p-SLG, were synthesized and their self
      assembly in various organic solvents in the absence and presence of metal ions
      was investigated. Gelation test revealed that o-SLG formed a thermotropic gel in
      many organic solvents, whilst p-SLG did not. When metal ions, such as Cu(2+),
      Zn(2+), Mg(2+), Ni(2+), were added, different behaviors were observed. The
      addition of Cu(2+) induced p-SLG to from an organogel. In the case of o-SLG, the
      addition of Cu(2+) and Mg(2+) ions maintained the gelating ability of the
      compound, whilst Zn(2+) and Ni(2+) ions destroyed the gel. In addition, the
      introduction of Cu(2+) ions caused the nanofiber gel to perform a chiral twist,
      whilst the Mg(2+) ions enhanced the fluorescence of the gel. More interestingly,
      the Mg(2+)-ion-mediated organogel showed differences in the fluorescence
      quenching by D- and L-tartaric acid, thus showing a chiral recognition ability.

PMID- 22416043
TI  - Exploring the anticancer activity of functionalized isoindigos: synthesis, drug
      like potential, mode of action and effect on tumor-induced xenografts.
AB  - Meisoindigo has been used as an indirubin substitute for the treatment of chronic
      myeloid leukemia (CML) for several years. In view of its poor solubility and
      erratic absorption, several investigations have focused on developing analogues
      with more desirable physicochemical profiles. Here, we investigated the structure
      activity relationship (SAR) of meisoindigo with respect to its antiproliferative
      activity on leukemic K562 cells and found that appending a phenalkyl side chain
      onto the lactam NH resulted in analogues that retained good activity.
      Furthermore, analogues in which the phenyl ring was substituted with a basic
      heterocycle were significantly more soluble than meisoindigo while retaining
      acceptable antiproliferative profiles. The most promising analogue (E)-1-(2-(4
      methylpiperazin-1-yl)ethyl)-[3,3'-biindolinylidene]-2,2'-dione (5-4) is more
      potent than meisoindigo across a panel of malignant cells, with at least 40 times
      greater solubility than meisoindigo, little or no tendency to aggregate in
      solution and capable of significantly extending the lifespans of animals with
      K562 induced xenografts. Mechanistically, it induced apoptotic cell death and
      disrupted the progression of K562 cells from the G(1)  to G(2)  phase. Taken
      together, our findings highlighted the feasibility of addressing the
      physicochemical deficits of the isoindigo scaffold by systematic modifications
      which was achieved without overt loss of growth inhibitory activity.

PMID- 22416045
TI  - Vestibular and motor contributions to mobility: limitations of seniors awaiting
      discharge from hospital care.
AB  - BACKGROUND AND PURPOSE: Following hospitalization, seniors are at risk of
      impaired mobility and increased risk of falling, which can lead to injuries and
      re-admission. The primary purpose of this paper was to evaluate the ability of
      hospitalized seniors to use vestibular inputs for balance control. The secondary
      purpose was to examine the influence of vestibular function and lower limb muscle
      strength on mobility. METHODS: Experimental and correlation designs were used.
      Patients (aged 65-90 years), preparing for discharge from an inpatient geriatric
      rehabilitation unit, were recruited. Vestibular control of standing balance was
      measured using the Clinical Test of Sensory Interaction for Balance (CTSIB).
      Mobility was measured with the Timed Up and Go (TUG) Test. Lower limb muscle
      maximum voluntary isometric contraction (MVIC) strength was tested with portable
      dynamometry. Wilcoxon signed rank test, with alpha adjusted for multiple
      comparisons (p <= 0.017), was used to compare relevant components of the CTSIB.
      Stepwise regression was used to assess the influence of vestibular impairment on
      TUG score. RESULTS: CTSIB(Test6) (median = 7.1 seconds, range = 0.0-30.0) was
      less than CTSIB(Test1) (30.0 seconds, 30.0-30.0) and CTSIB(Test4) (30.0 seconds,
      10.5-30.0) (W = 136, p < 0.017). MVIC scores (Nm.kg-1, mean +/- SD) included hip
      abduction 0.38 +/- 0.2, hip flexion 0.32 +/- 0.1, hip extension 0.44 +/- 0.2,
      knee flexion 0.31 +/- 0.1, knee extension 0.33 +/- 0.2, ankle dorsiflexion 0.12
      +/- 0.1 and ankle plantarflexion 0.23 +/- 0.1. Mean TUG score was 26.1 +/- 6.0
      seconds. Performance on CTSIB(Test6) explained 55% of the variance in TUG scores,
      whereas hip extension strength explained an additional 6%. CONCLUSIONS: Seniors
      awaiting discharge from hospital had impaired vestibular control of balance that
      was systematically associated with impaired mobility. Evaluating vestibular
      function prior to discharge from hospital could improve discharge planning with
      respect to management of impairments that threaten balance and safe mobility.

PMID- 22416046
TI  - Gas-phase thermodynamics as a validation of computational catalysis on surfaces:
      a case study of Fischer-Tropsch synthesis.
AB  - Density functional theory has become a valuable tool to study surface catalysis.
      However, due to the scarcity of clean and reliable experimental data on surfaces,
      the theoretical methods employed to explore heterogeneous catalytic mechanisms
      are usually less well validated than those for gas-phase reactions. We argue
      herein that gas-phase reactions and the corresponding surface reactions are
      related through the Born-Haber cycle and computational catalysis on surfaces will
      be less meaningful if gas-phase behavior cannot first be suitably determined. In
      this contribution, we have constructed a set of gas-phase reactions relevant to
      the Fischer-Tropsch synthesis as a case study. With this set, we have tested the
      validity of the widely used PBE and B3LYP functionals and found that neither of
      them are capable of describing all kinds of gas-phase reactions properly, such
      that some surface reactions may be biased falsely against the others.
      Significantly, XYG3, which is a double-hybrid functional that includes Hartree
      Fock-like exchange and many-body perturbation correlation effects, presents a
      significant improvement for all of the gas-phase reactions, holding promise for
      further development for surface catalysis.

PMID- 22416044
TI  - HDL mimetics inhibit tumor development in both induced and spontaneous mouse
      models of colon cancer.
AB  - Recent studies suggest that high-density lipoprotein (HDL) levels are inversely
      related to colon cancer risk. HDL mimetics constructed from a number of peptides
      and proteins with varying structures possess anti-inflammatory and antioxidant
      properties reminiscent of HDL. In this article, we examined whether HDL mimetics,
      L-4F (an apolipoprotein A-I mimetic peptide) and G* (an apolipoprotein J mimetic
      peptide) affect tumor growth and development in mouse models of colon cancer. HDL
      mimetics reduced viability and proliferation of CT26 cells, a mouse colon
      adenocarcinoma cell line, and decreased CT26 cell-mediated tumor burden in BALB/c
      mice when administered subcutaneously or orally. Plasma levels of
      lysophosphatidic acid (LPA), a serum biomarker for colon cancer, were
      significantly reduced in mice that received HDL mimetics, suggesting that binding
      and removal of proinflammatory lipids is a potential mechanism for the inhibition
      of tumor development by HDL mimetics. Furthermore, L-4F significantly reduced
      size and number of polyps in APC(min/+) mice, a mouse model for human familial
      adenomatous polyposis, suggesting that HDL mimetics are effective in inhibiting
      the development of both induced and spontaneous cancers of the colon. Our
      results, for the first time, identify HDL mimetics as a novel therapeutic
      strategy for the treatment of colon cancer.

PMID- 22416047
TI  - Observ-OM and Observ-TAB: Universal syntax solutions for the integration, search,
      and exchange of phenotype and genotype information.
AB  - Genetic and epidemiological research increasingly employs large collections of
      phenotypic and molecular observation data from high quality human and model
      organism samples. Standardization efforts have produced a few simple formats for
      exchange of these various data, but a lightweight and convenient data
      representation scheme for all data modalities does not exist, hindering
      successful data integration, such as assignment of mouse models to orphan
      diseases and phenotypic clustering for pathways. We report a unified system to
      integrate and compare observation data across experimental projects, disease
      databases, and clinical biobanks. The core object model (Observ-OM) comprises
      only four basic concepts to represent any kind of observation: Targets, Features,
      Protocols (and their Applications), and Values. An easy-to-use file format
      (Observ-TAB) employs Excel to represent individual and aggregate data in
      straightforward spreadsheets. The systems have been tested successfully on human
      biobank, genome-wide association studies, quantitative trait loci, model
      organism, and patient registry data using the MOLGENIS platform to quickly setup
      custom data portals. Our system will dramatically lower the barrier for future
      data sharing and facilitate integrated search across panels and species. All
      models, formats, documentation, and software are available for free and open
      source (LGPLv3) at http://www.observ-om.org.

PMID- 22416048
TI  - Structure-based design of novel pyrimido[4,5-c]pyridazine derivatives as
      dihydropteroate synthase inhibitors with increased affinity.
AB  - Dihydropteroate synthase (DHPS) is the validated drug target for sulfonamide
      antimicrobial therapy. However, due to widespread drug resistance and poor
      tolerance, the use of sulfonamide antibiotics is now limited. The pterin binding
      pocket in DHPS is highly conserved and is distinct from the sulfonamide binding
      site. It therefore represents an attractive alternative target for the design of
      novel antibacterial agents. We previously carried out the structural
      characterization of a known pyridazine inhibitor in the Bacillus anthracis DHPS
      pterin site and identified a number of unfavorable interactions that appear to
      compromise binding. With this structural information, a series of 4,5-dioxo
      1,4,5,6-tetrahydropyrimido[4,5-c]pyridazines were designed to improve binding
      affinity. Most importantly, the N-methyl ring substitution was removed to improve
      binding within the pterin pocket, and the length of the side chain carboxylic
      acid was optimized to fully engage the pyrophosphate binding site. These
      inhibitors were synthesized and evaluated by an enzyme activity assay, X-ray
      crystallography, isothermal calorimetry, and surface plasmon resonance to obtain
      a comprehensive understanding of the binding interactions from structural,
      kinetic, and thermodynamic perspectives. This study clearly demonstrates that
      compounds lacking the N-methyl substitution exhibit increased inhibition of DHPS,
      but the beneficial effects of optimizing the side chain length are less apparent.

PMID- 22416049
TI  - Bioinspired electrospun knotted microfibers for fog harvesting.

PMID- 22416050
TI  - An efficient synthesis of quinoxalinone derivatives as potent inhibitors of
      aldose reductase.
AB  - A novel and facile synthesis of quinoxalinone derivatives was developed in which
      a wide range of 3-chloroquinoxalin-2(1H)-ones as key intermediates can be
      generated chemo- and regioselectively in good yields from corresponding
      quinoxaline-2,3(1H,4H)-diones. This new protocol is arguably superior, as it
      allows the design and preparation of a variety of bioactive quinoxaline-based
      compounds, which are particularly effective in the treatment of diabetes and its
      complications. Through this procedure, a new class of quinoxalinone-based aldose
      reductase inhibitors were synthesized successfully. Most of the inhibitors, with
      an N1-acetic acid head group and a substituted C3-phenoxy side chain, proved to
      be potent and selective. Their IC(50) values ranged from 11.4 to 74.8 nM. Among
      them, 2-(3-(4-bromophenoxy)-7-fluoro-2-oxoquinoxalin-1(2H)-yl)acetic acid and 2
      (6-bromo-3-(4-bromophenoxy)-2-oxoquinoxalin-1(2H)-yl)acetic acid were the most
      active. Structure-activity relationship and molecular docking studies highlighted
      the importance of the ether spacer in the C3-phenoxy side chains, and provided
      clear guidance on the contribution of substitutions both at the core structure
      and the side chain to activity.

PMID- 22416051
TI  - From single molecule to crystal: mapping out the conformations of tartaric acids
      and their derivatives.
AB  - Stereoisomers of one of the most important organic compounds, tartaric acid,
      optically active and meso as well as the ester or amide derivatives, can show
      diverse structures related to the rotation around the three carbon-carbon bonds.
      This study determines the controlling factors for conformational changes of these
      molecules in vacuo, in solution, and in the crystalline state using DFT
      calculations, spectroscopic measurements, and X-ray diffraction. All structural
      variations can be logically accounted for by the possibility of formation and
      breaking of hydrogen bonds between the hydroxy or amide donors and oxygen
      acceptors, among these the hydrogen bonds that close five-membered rings being
      the most stable. These findings are useful in designing molecular and crystal
      structures of highly polar, polyfunctional, chiral compounds.

PMID- 22416052
TI  - Receptor conformations involved in dopamine D(2L) receptor functional selectivity
      induced by selected transmembrane-5 serine mutations.
AB  - Although functional selectivity is now widely accepted, the molecular basis is
      poorly understood. We have studied how aspects of transmembrane region 5 (TM5) of
      the dopamine D(2L) receptor interacts with three rationally selected rigid
      ligands (dihydrexidine, dinapsoline, and dinoxyline) and the reference compounds
      dopamine and quinpirole. As was expected from homology modeling, mutation of
      three TM5 serine residues to alanine (S5.42A, S5.43A, S5.46A) had little effect
      on antagonist affinity. All three mutations decreased the affinity of the agonist
      ligands to different degrees, S5.46A being somewhat less affected. Four functions
      [adenylate cyclase (AC), extracellular signal-regulated kinase 1/2
      phosphorylation (MAPK), arachidonic acid release (AA), and guanosine 5'-O-(3
      thio)triphosphate binding (GTPgammaS)] were assessed. The intrinsic activity (IA)
      of quinpirole was unaffected by any of the mutations, whereas S5.42A and S5.46A
      mutations abolished the activity of dopamine and the three rigid ligands,
      although dihydrexidine retained IA at MAPK function only with S5.42A. Remarkably,
      S5.43A did not markedly affect IA for AC and MAPK for any of the ligands and
      eliminated AA activity for dinapsoline and dihydrexidine but not dinoxyline.
      These data suggest that this mutation did not disrupt the overall conformation or
      signaling ability of the mutant receptors but differentially affected ligand
      activation. Computational studies indicate that these D(2) agonists stabilize
      multiple receptor conformations. This has led to models showing the stabilized
      conformations and interhelical and receptor-ligand contacts corresponding to the
      different activation pathways stabilized by various agonists. These data provide
      a basis for understanding D(2L) functional selectivity and rationally discovering
      functionally selective D(2) drugs.

PMID- 22416053
TI  - Fluoroquinolone use and fluoroquinolone-resistant Pseudomonas aeruginosa is
      declining in US academic medical centre hospitals.

PMID- 22416054
TI  - Efficacy of telavancin in patients with specific types of complicated skin and
      skin structure infections.
AB  - BACKGROUND: Telavancin is approved in the USA and Canada for the treatment of
      Gram-positive complicated skin and skin structure infections (cSSSIs) based on
      the results of the Phase 3 Assessment of TeLAvancin in complicated Skin and skin
      structure infections (ATLAS) trials, which demonstrated non-inferiority of
      telavancin to vancomycin. METHODS: We conducted a post hoc analysis of the ATLAS
      studies (ClinicalTrials.gov identifiers NCT00091819 and NCT00107978) to explore
      the efficacy of telavancin in patients with various types of cSSSIs. RESULTS: A
      total of 1794 patients were included in this analysis; 1434 patients were
      clinically evaluable (CE) and 563 of these had methicillin-resistant
      Staphylococcus aureus (MRSA). Among CE patients with major abscesses (n = 619),
      cure rates were 91% for telavancin and 90% for vancomycin (95% CI for the
      difference -3.6 to 5.7). In patients with infective cellulitis (n = 519), cure
      was achieved in 87% and 88% of telavancin- and vancomycin-treated patients,
      respectively (95% CI for the difference -6.2 to 5.2). Cure rates in patients with
      wound infections were 85% in the telavancin group and 86% in the vancomycin group
      (95% CI for the difference -10.5 to 9.0). Cure rates for each type of cSSSI in
      patients infected with MRSA were also similar between the two treatment arms.
      Among CE patients infected with Panton-Valentine leucocidin (PVL)-positive MRSA
      (n = 447), cure rates were 93% for telavancin and 90% for vancomycin (95% CI for
      the difference -2.2 to 8.2). CONCLUSIONS: Cure rates were similar for telavancin
      and vancomycin in patients with different types of cSSSIs, including infections
      caused by MRSA and PVL-positive strains of MRSA.

PMID- 22416055
TI  - Charge matching on designing neutral cadmium-lanthanide-organic open frameworks
      for luminescence sensing.
AB  - Through careful consideration of charge matching, a simple replacement of metal
      ion from Cd(2+) to Ln(3+) in a building unit successfully transforms an anionic
      microporous framework into a series of isostructural porous neutral
      heterometallic frameworks [Cd(3)Ln(2)(btc)(4)(H(2)O)(6)(dmf)(4)].x(solvent) (1;
      Ln=Tb, Eu, Nd, Gd, Sm, dmf=N,N'-dimethylformamide) by employing five different
      lanthanide ions. 1-Tb and 1-Eu exhibit interesting photoluminescent properties,
      and remarkably, 1-Tb can act as a luminescent sensor to identify organic solvents
      and metal ions.

PMID- 22416056
TI  - Reaction of "non-symmetrical" 1,2,4-trithiolanes with [(phosphane)Pt(0)(eta2
      nbe)] complexes.
AB  - Two unsymmetrical 1,2,4-trithiolanes (1d and 1e) were reacted with
      [Pt(0)(PPh(3))(2)(eta(2)-nbe)] (6; nbe=norborn-2-ene) and [Pt(0)(dppn)(eta(2)
      nbe)] (11; dppn=1,8-bis(diphenylphosphanyl)naphthalene)), respectively. Their
      treatment with compound 6 resulted in the formation of six-membered platinacycles
      of type 7, which selectively underwent fragmentation into dithiolato complexes
      and thiobenzophenone (4b). The isolation of the first stable C-substituted member
      of this class of compounds (i.e., compound 7e) permitted kinetic studies of this
      process by using UV/Vis spectroscopy. These results, together with DFT
      calculations, allowed us to propose a mechanism for the reactions of compound 6
      with 1,2,4-trithiolanes. In contrast, similar treatment of compound 11 with
      compounds 1d and 1e at room temperature did not result in any reaction. Heating
      the appropriate samples to 110  degrees C led to the formation of dithiolato
      complexes and eta(2)-thioketone compounds, thus pointing to a thermally induced
      [3+2]-cycloreversion of the heterocycles as an initial step of the reaction.

PMID- 22416057
TI  - 900 MHz radiation does not induce micronucleus formation in different cell types.
AB  - The exposure of the population to non-ionising electromagnetic radiation is still
      increasing, mainly due to mobile communication. Whether low-intensity
      electromagnetic fields can cause other effects apart from heating has been a
      subject of debate. One of the effects, which were proposed to be caused by mobile
      phone radiation, is the occurrence of mitotic disturbances. The aim of this study
      was to investigate possible consequences of these mitotic disturbances as
      manifest genomic damage, i.e. micronucleus induction. Cells were irradiated at a
      frequency of 900 MHz, which is located in one of the main frequency bands applied
      for mobile communication. Two cell types were used, HaCaT cells as human cells
      and A(L) cells (human-hamster hybrid cells), in which mitotic disturbances had
      been reported to occur. After different post-exposure incubation periods, cells
      were fixed and micronucleus frequencies were evaluated. Both cell types did not
      show any genomic damage after exposure. To adapt the protocol for the
      micronucleus test into the direction of the protocol for mitotic disturbances,
      the post-exposure incubation period was reduced and exposure time was extended to
      one cell cycle length. This did not result in any increase of the genomic damage.
      In conclusion, micronucleus induction was not observed as a consequence of
      exposure to non-ionising radiation, even though this agent was reported to cause
      mitotic disturbances under similar experimental conditions.

PMID- 22416058
TI  - "No struggle, no fight, no court battle": the 1948 desegregation of the
      University of Arkansas School of Medicine.
AB  - In 1948, over 30 percent of the approved medical schools in the United States
      excluded black students. However, on September 10, 1948, the University of
      Arkansas School of Medicine became the first Southern medical school to
      desegregate when Edith Mae Irby matriculated. Her admission occurred without
      incident. There were no jeering white mobs, no court action, and no federal
      troops. Irby's admission had its roots in a successful legal campaign launched by
      the National Association for the Advancement of Colored People to eradicate
      racial inequalities in professional and graduate education. A confluence of
      factors led the University of Arkansas to desegregate. These included the state's
      lack of the financial resources necessary to comply with U.S. Supreme Court
      decisions, a climate of racial moderation in Arkansas, shrewd political
      maneuvering by officials at the University of Arkansas, and Irby's academic
      accomplishments. Irby's historic admission is frequently overlooked as a
      historical milestone. Its invisibility is due in part to its sharp contrast to
      the dominant narratives of school desegregation in the South. Yet, the story of
      Irby's entrance into medical school is critical for a more complete understanding
      of the history of medical education and the civil rights movement.

PMID- 22416059
TI  - Evaluation of a peer led parenting intervention for disruptive behaviour problems
      in children: community based randomised controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of a peer led parenting intervention
      delivered to socially disadvantaged families. DESIGN: Randomised controlled
      trial. SETTING: Schools and children's centres in a socially deprived borough of
      inner London. PARTICIPANTS: Parental caregivers seeking help with managing the
      problem behaviours of 116 index children, aged 2-11 years; 59 families were
      randomised to the intervention and 57 to a waitlist control condition.
      INTERVENTION: Empowering parents, empowering communities is an eight week (two
      hours each week), manualised programme delivered to groups of parents by trained
      peer facilitators from the local community. MAIN OUTCOME MEASURES: Child problems
      (number and severity), parental stress, and parenting competencies were assessed
      before and after the intervention using standardised parent reported measures.
      RESULTS: Significantly greater improvements in positive parenting practices and
      child problems were observed in the intervention group compared with the waitlist
      group, with no difference in parental stress between the groups. An intention to
      treat analysis for the primary outcome measure, the intensity subscale of the
      Eyberg child behaviour inventory, showed an intervention effect size of 0.38 (95%
      confidence interval 0.01 to 0.75, P=0.01). The intervention group had high rates
      of treatment retention (91.5%) and user satisfaction. CONCLUSION: The peer led
      parenting intervention significantly reduced child behaviour problems and
      improved parenting competencies. This is a promising method for providing
      effective and acceptable parenting support to families considered hard to reach
      by mainstream services. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN01962337.

PMID- 22416060
TI  - Peer led parenting support programmes.

PMID- 22416061
TI  - Patient safety in developing countries: retrospective estimation of scale and
      nature of harm to patients in hospital.
AB  - OBJECTIVE: To assess the frequency and nature of adverse events to patients in
      selected hospitals in developing or transitional economies. DESIGN: Retrospective
      medical record review of hospital admissions during 2005 in eight countries.
      SETTING: Ministries of Health of Egypt, Jordan, Kenya, Morocco, Tunisia, Sudan,
      South Africa and Yemen; the World Health Organisation (WHO) Eastern Mediterranean
      and African Regions (EMRO and AFRO), and WHO Patient Safety. PARTICIPANTS:
      Convenience sample of 26 hospitals from which 15,548 patient records were
      randomly sampled. MAIN OUTCOME MEASURES: Two stage screening. Initial screening
      based on 18 explicit criteria. Records that screened positive were then reviewed
      by a senior physician for determination of adverse event, its preventability, and
      the resulting disability. RESULTS: Of the 15,548 records reviewed, 8.2% showed at
      least one adverse event, with a range of 2.5% to 18.4% per country. Of these
      events, 83% were judged to be preventable, while about 30% were associated with
      death of the patient. About 34% adverse events were from therapeutic errors in
      relatively non-complex clinical situations. Inadequate training and supervision
      of clinical staff or the failure to follow policies or protocols contributed to
      most events. CONCLUSIONS: Unsafe patient care represents a serious and
      considerable danger to patients in the hospitals that were studied, and hence
      should be a high priority public health problem. Many other developing and
      transitional economies will probably share similar rates of harm and similar
      contributory factors. The convenience sampling of hospitals might limit the
      interpretation of results, but the identified adverse event rates show an
      estimate that should stimulate and facilitate the urgent institution of
      appropriate remedial action and also to trigger more research. Prevention of
      these adverse events will be complex and involves improving basic clinical
      processes and does not simply depend on the provision of more resources.

PMID- 22416062
TI  - Strategies to prevent airway complications: a survey of adult intensive care
      units in Australia and New Zealand.
AB  - BACKGROUND: There is growing evidence that airway complications are relatively
      common in critical care. Strategies have been suggested to decrease their
      incidence. METHODS: We conducted a telephone survey of all adult intensive care
      units (ICUs) in Australia and New Zealand to establish the current practice
      regarding strategies used to reduce airway complications in five key areas: (i)
      use of capnography; (ii) care of oral tracheal tubes; (iii) care of tracheostomy
      tubes; (iv) difficult and failed intubation; and (v) training and medical
      staffing. RESULTS: Of 176 ICU meeting inclusion criteria, 171 agreed to
      participate. Capnography is used during tracheal intubation in 88% of ICUs and
      for continuous monitoring in 64%. Protocols for advancing or partially
      withdrawing malpositioned tracheal tubes are used by 54% of units, with most
      allowing repositioning by unaccredited nurses. A small minority of ICUs use bed
      head signs to identify patients with 'critical airways' or laryngectomy, while
      only 8% have specific protocols for the care of these high-risk patients.
      Tracheostomy emergency algorithms are available in 13% of ICUs. At night, a
      doctor is exclusively assigned to 73% of units, although in 72%, the night doctor
      is not required to have prior anaesthetic/airway training. In 97% of the
      institutions surveyed, the senior doctor relied upon for airway emergencies at
      night is either non-resident or working elsewhere in the hospital. CONCLUSIONS:
      Our data suggest that several possible strategies for avoiding airway
      complications in ICU patients dependent on an artificial airway are poorly
      implemented. This may expose these patients to avoidable risk.

PMID- 22416063
TI  - A pharmacodynamic study of the P-glycoprotein antagonist CBT-1(r) in combination
      with paclitaxel in solid tumors.
AB  - BACKGROUND: This pharmacodynamic trial evaluated the effect of CBT-1(r) on efflux
      by the ATP binding cassette (ABC) multidrug transporter P-glycoprotein
      (Pgp/MDR1/ABCB1) in normal human cells and tissues. CBT-1(r) is an orally
      administered bisbenzylisoquinoline Pgp inhibitor being evaluated clinically.
      Laboratory studies showed potent and durable inhibition of Pgp, and in phase I
      studies CBT-1(r) did not alter the pharmacokinetics of paclitaxel or doxorubicin.
      METHODS: CBT-1(r) was dosed at 500 mg/m2 for 7 days; a 3-hour infusion of
      paclitaxel at 135 mg/m2 was administered on day 6. Peripheral blood mononuclear
      cells (PBMCs) were obtained prior to CBT-1(r) administration and on day 6 prior
      to the paclitaxel infusion. (99m)Tc-sestamibi imaging was performed on the same
      schedule. The area under the concentration-time curve from 0-3 hours (AUC(0-3))
      was determined for (99m)Tc-sestamibi. RESULTS: Twelve patients were planned and
      enrolled. Toxicities were minimal and related to paclitaxel (grade 3 or 4
      neutropenia in 18% of cycles). Rhodamine efflux from CD56+ PBMCs was a
      statistically significant 51%-100% lower (p < .0001) with CBT-1(r). Among 10
      patients who completed imaging, the (99m)Tc-sestamibi AUC(0-3) for liver
      (normalized to the AUC(0-3) of the heart) increased from 34.7% to 100.8% (median,
      71.9%; p < .0001) after CBT-1(r) administration. Lung uptake was not changed.
      CONCLUSION: CBT-1(r) is able to inhibit Pgp-mediated efflux from PBMCs and normal
      liver to a degree observed with Pgp inhibitors studied in earlier clinical
      trials. Combined with its ease of administration and lack of toxicity, the data
      showing inhibition of normal tissue Pgp support further studies with CBT-1(r) to
      evaluate its ability to modulate drug uptake in tumor tissue. DISCUSSION:
      Although overexpression of ABCB1 and other ABC transporters has been linked with
      poor outcome following chemotherapy efforts to negate that through pharmacologic
      inhibition have generally failed. This is thought to be a result of several
      factors, including (a) failure to select patients with tumors in which ABCB1 is a
      dominant resistance mechanism; (b) inhibitors that were not potent, or that
      impaired drug clearance; and (c) the existence of other mechanisms of drug
      resistance, including other ABC transporters. Although an animal model for Pgp
      has been lacking, recent studies have exploited a Brca1(-/-); p53(-/-) mouse
      model of hereditary breast cancer that develops sporadic tumors similar to
      cancers in women harboring BRCA1 mutations. Treatment with doxorubicin,
      docetaxel, or the poly(ADP-ribose) polymerase inhibitor olaparib brings about
      shrinkage, but resistance eventually emerges. Overexpression of the Abcb1a gene,
      the mouse ortholog of human ABCB1, has been shown to be a mechanism of resistance
      in a subset of these tumors. Treating mice with resistant tumors with olaparib
      plus the Pgp inhibitor tariquidar resensitized the tumors to olaparib. Although
      results in this animal model support a new look at Pgp as a target, in this era
      of "targeted therapies," trial designs that directly assess modulation of drug
      uptake, including quantitative nuclear imaging, should be pursued before clinical
      efficacy assessments are undertaken. Such assessment should be performed with
      compounds that inhibit tissue Pgp without altering the pharmacokinetics of
      chemotherapeutic agents. This pharmacodynamic study demonstrated that CBT-1(r),
      inhibits Pgp-mediated efflux from PBMCs and normal liver.

PMID- 22416064
TI  - Sequence dependence of isothermal DNA amplification via EXPAR.
AB  - Isothermal nucleic acid amplification is becoming increasingly important for
      molecular diagnostics. Therefore, new computational tools are needed to
      facilitate assay design. In the isothermal EXPonential Amplification Reaction
      (EXPAR), template sequences with similar thermodynamic characteristics perform
      very differently. To understand what causes this variability, we characterized
      the performance of 384 template sequences, and used this data to develop two
      computational methods to predict EXPAR template performance based on sequence: a
      position weight matrix approach with support vector machine classifier, and
      RELIEF attribute evaluation with Naive Bayes classification. The methods
      identified well and poorly performing EXPAR templates with 67-70% sensitivity and
      77-80% specificity. We combined these methods into a computational tool that can
      accelerate new assay design by ruling out likely poor performers. Furthermore,
      our data suggest that variability in template performance is linked to specific
      sequence motifs. Cytidine, a pyrimidine base, is over-represented in certain
      positions of well-performing templates. Guanosine and adenosine, both purine
      bases, are over-represented in similar regions of poorly performing templates,
      frequently as GA or AG dimers. Since polymerases have a higher affinity for
      purine oligonucleotides, polymerase binding to GA-rich regions of a single
      stranded DNA template may promote non-specific amplification in EXPAR and other
      nucleic acid amplification reactions.

PMID- 22416066
TI  - Efficient motif search in ranked lists and applications to variable gap motifs.
AB  - Sequence elements, at all levels-DNA, RNA and protein, play a central role in
      mediating molecular recognition and thereby molecular regulation and signaling.
      Studies that focus on -measuring and investigating sequence-based recognition
      make use of statistical and computational tools, including approaches to
      searching sequence motifs. State-of-the-art motif searching tools are limited in
      their coverage and ability to address large motif spaces. We develop and present
      statistical and algorithmic approaches that take as input ranked lists of
      sequences and return significant motifs. The efficiency of our approach, based on
      suffix trees, allows searches over motif spaces that are not covered by existing
      tools. This includes searching variable gap motifs-two half sites with a flexible
      length gap in between-and searching long motifs over large alphabets. We used our
      approach to analyze several high-throughput measurement data sets and report some
      validation results as well as novel suggested motifs and motif refinements. We
      suggest a refinement of the known estrogen receptor 1 motif in humans, where we
      observe gaps other than three nucleotides that also serve as significant
      recognition sites, as well as a variable length motif related to potential
      tyrosine phosphorylation.

PMID- 22416065
TI  - Genome-wide polycomb target gene prediction in Drosophila melanogaster.
AB  - As key epigenetic regulators, polycomb group (PcG) proteins are responsible for
      the control of cell proliferation and differentiation as well as stem cell
      pluripotency and self-renewal. Aberrant epigenetic modification by PcG is
      strongly correlated with the severity and invasiveness of many types of cancers.
      Unfortunately, the molecular mechanism of PcG-mediated epigenetic regulation
      remained elusive, partly due to the extremely limited pool of experimentally
      confirmed PcG target genes. In order to facilitate experimental identification of
      PcG target genes, here we propose a novel computational method, EpiPredictor,
      that achieved significantly higher matching ratios with several recent chromatin
      immunoprecipitation studies than jPREdictor, an existing computational method. We
      further validated a subset of genes that were uniquely predicted by EpiPredictor
      by cross-referencing existing literature and by experimental means. Our data
      suggest that multiple transcription factor networking at the cis-regulatory
      elements is critical for PcG recruitment, while high GC content and high
      conservation level are also important features of PcG target genes. EpiPredictor
      should substantially expedite experimental discovery of PcG target genes by
      providing an effective initial screening tool. From a computational standpoint,
      our strategy of modelling transcription factor interaction with a non-linear
      kernel is original, effective and transferable to many other applications.

PMID- 22416067
TI  - Analysis of lysine recognition and specificity of the Bacillus subtilis L box
      riboswitch.
AB  - The ever-changing environment of a bacterial cell requires sophisticated
      mechanisms to adjust gene expression in response to changes in nutrient
      availability. L box riboswitch RNAs regulate gene expression in response to
      cellular lysine (lys) concentrations in the absence of additional regulatory
      factors. In Bacillus subtilis, binding of lysine (lys) to the L box RNA causes
      premature transcription termination in the leader region upstream of the lysC
      coding sequence. To date, little is known about the specific RNA-lys interactions
      required for transcription termination. In this study, we characterize features
      of the B. subtilis lysC leader RNA responsible for lys specificity, and
      structural elements of the lys molecule required for recognition. The wild-type
      lysC leader RNA can recognize and discriminate between lys and lys analogs. We
      identified leader RNA variants with mutations in the lys-binding pocket that
      exhibit changes in the specificity of ligand recognition. These data demonstrate
      that lysC leader RNA specificity is the result of recognition of ligand features
      through a series of distinct interactions between lys and nucleotides that
      comprise the lys-binding pocket, and provide insight into the molecular
      mechanisms employed by L box riboswitch RNAs to bind and recognize lys.

PMID- 22416070
TI  - GSK3, snail, and adhesion molecule regulation by cyclosporine A in renal tubular
      cells.
AB  - Tubular cell injury and fibrosis are key features of calcineurin inhibitor
      nephrotoxicity, but the molecular processes involved are not fully understood. In
      cultured murine MCT and human kidney 2 proximal tubular cells, gene expression
      and protein levels were studied by real-time polymerase chain reaction, Western
      blot, and confocal microscopy. Protein function was evaluated by pharmacological
      inhibitors and confirmed by small interfering RNA (siRNA) gene targeting. In
      renal tubular cells, cytotoxic concentrations of cyclosporine A (CsA) inhibited
      both gene and protein expression of adherent and tight junction proteins (E
      cadherin, ZO-1, claudin-1, and beta-catenin) and increased vimentin expression,
      without involvement of transforming growth factor beta1 or caspase activity. CsA
      upregulated transcriptional repressors (Snail, Slug, and Twist) of the adherent
      and tight junction proteins were studied. Snail siRNA targeting prevented the
      downregulation of E-cadherin by CsA. CsA promoted glycogen synthase kinase 3
      (GSK3) phosphorylation and increased Snail half-life. The GSK3 inhibitor lithium
      upregulated Snail and decreased E-cadherin expression in a Snail-dependent
      manner. Moreover, targeting GSK3 activity by siRNA also upregulated Snail.
      Furthermore, GSK3 siRNA had a negative impact on CsA-induced upregulation of
      Snail. Tacrolimus also inhibited GSK3 and mimicked CsA responses in tubular
      cells. We conclude that calcineurin inhibitors may directly decrease the
      expression of epithelial adhesion molecules by repressing GSK3 and stabilizing
      Snail. This offers potential pharmacological targets for prevention of
      nephrotoxicity.

PMID- 22416072
TI  - Bryostatin analog: improving on Nature's design.

PMID- 22416071
TI  - Down selection of polymerized bovine hemoglobins for use as oxygen releasing
      therapeutics in a guinea pig model.
AB  - Hemoglobin (Hb)-based oxygen carriers (HBOCs) are being developed as
      resuscitative fluids for use in multiple medical applications and in lieu of
      blood transfusion. However, cardiovascular, central nervous system, and renal
      adverse events have largely impeded progress. This has prompted a need to
      evaluate novel down selection approaches for HBOCs prior to in-depth preclinical
      and clinical safety testing. In the present study, polymerized bovine Hbs
      (PolybHbs) were prepared with increasing ratios of glutaraldehyde to bovine Hb
      (10:1, 20:1, 30:1, and 40:1). The optimal PolybHb candidate selection was based
      on a priori determined in vivo response to include a long circulating PolybHb
      with no measurable renal exposure, minimal cardiovascular response, limited
      oxidation to metHb in vitro, or in circulation and absence of acute end organ
      toxicity. Guinea pigs were dosed via a 50% blood for PolybHb exchange
      transfusion. Data suggested that the 30:1 preparation exhibited maximum
      circulatory exposure (AUC(0)(-infinity)) with the lowest level of oxidation
      (plasma metHb formation) and minimal (< 10%) blood pressure elevation.
      Additionally, the 30:1 preparation was absent renal iron deposition as well as
      abnormal glomerular/tubular histopathology or serum creatinine elevation.
      Clearance pathways predominantly followed those consistent with endogenous Hb
      clearance based pathways. Therefore, data confirmed the ability to select a
      single PolybHb from a small library of HBOCs based on a priori determined
      characteristics. Moreover, the approach to down selection described could be
      applied to enhance the early predictability of human safety for this class of
      biological therapeutics to optimize for specific indications.

PMID- 22416075
TI  - Ventricular rupture in Takotsubo cardiomyopathy.

PMID- 22416074
TI  - The rise of cardiovascular medicine.
AB  - Modern cardiology was born at the turn of the nineteenth to twentieth centuries
      with three great discoveries: the X ray, the sphygmomanometer, and the
      electrocardiograph. This was followed by cardiac catheterization, which led to
      coronary angiography and to percutaneous coronary intervention. The coronary care
      units and early reperfusion reduced the early mortality owing to acute myocardial
      infarction, and the discovery of coronary risk factors led to the development of
      Preventive Cardiology. Other major advances include several cardiac imaging
      techniques, the birth and development of cardiac surgery, and the control of
      cardiac arrhythmias. The treatment of heart failure, although greatly improved,
      remains a challenge. Current cardiology practice is evidence-based and global in
      scope. Research and practice are increasingly conducted in cardiovascular centres
      and institutes. It is likely that in the future, a greater emphasis will be
      placed on prevention, which will be enhanced by genetic information.

PMID- 22416076
TI  - The apple does not fall far from the tree: epicardial ventricular tachycardia due
      to blunt chest trauma.

PMID- 22416077
TI  - Adaptation of ghrelin and the GH/IGF axis to high altitude.
AB  - OBJECTIVE: High altitude (HA) provokes a variety of endocrine adaptive processes.
      We investigated the impact of HA on ghrelin levels and the GH/IGF axis. DESIGN:
      Observational study as part of a medical multidisciplinary project in a
      mountainous environment. METHODS: Thirty-three probands (12 females) were
      investigated at three timepoints during ascent to HA (A: d -42, 120 m; B: d +4,
      3440 m; C: d +14, 5050 m). The following parameters were obtained: ghrelin; GH;
      GH-binding protein (GHBP); IGF1; IGF2; IGF-binding proteins (IGFBPs) -1, -2, and 
      3; acid-labile subunit (ALS); and insulin. Weight was monitored and general well
      being assessed using the Lake Louise acute mountain sickness (AMS) score.
      RESULTS: Ghrelin (150 VS 111PG/ML; P0.01) and GH (3.4 VS 1.7G/L; P0.01) were
      significantly higher at timepoint C compared with A whereas GHBP, IGF1, IGF2,
      IGFBP3, ALS, and insulin levels did not change. IGFBP1 (58 VS 47G/L; P0.05) and,
      even more pronounced, IGFBP2 (1141 VS 615G/L; P0.001) increased significantly. No
      correlation, neither sex-specific nor in the total group, between individual
      weight loss (females: -2.1 kg; males: -5.1 kg) and rise in ghrelin was found.
      Five of the subjects did not reach investigation point C due to AMS. CONCLUSIONS:
      After 14 days of exposure to HA, we observed a significant ghrelin and GH
      increase without changes in GHBP, IGF1, IGF2, IGFBP3, ALS, and insulin. Higher GH
      seems to be needed for acute metabolic effects rather than IGF/IGFBP3 generation.
      Increased IGFBP1 and -2 may reflect effects from HA on IGF bioavailability.

PMID- 22416078
TI  - Arrest of atherosclerosis progression after interruption of GH replacement in
      adults with congenital isolated GH deficiency.
AB  - OBJECTIVE: GH replacement therapy (GHRT) in adult-onset GH deficiency (AOGHD)
      reduces carotid intima-media thickness (IMT) and increases myocardial mass, with
      improvement of systolic and diastolic function. These observations have
      reinforced the use of GHRT on AOGHD. Conversely, we have previously reported that
      in adults with lifetime congenital and severe isolated GH deficiency (IGHD) due
      to a mutation in GHRH receptor gene (GHRHR), a 6-month treatment with depot GH
      increased carotid IMT, caused the development of atherosclerotic plaques, and an
      increase in left ventricular mass index (LVMI), posterior wall, and septal
      thickness and ejection fraction. Such effects persisted 12 months after treatment
      (12-month washout - 12 mo). METHODS: We have studied the cardiovascular status
      (by echocardiography and carotid ultrasonography) of these subjects 60 months
      after completion of therapy (60-month washout - 60 mo). RESULTS: Carotid IMT
      reduced significantly from 12 to 60 mo, returning to baseline (pre-therapy)
      value. The number of individuals with plaques was similar at 12 and 60 mo,
      remaining higher than pre-therapy. LVMI, relative posterior wall thickness, and
      septum thickness did not change between 12 and 60 mo, but absolute posterior wall
      increased from 12 to 60 mo. Systolic function, evaluated by ejection fraction and
      shortening fraction, was reduced at 60 mo in comparison with 12 mo returning to
      baseline levels. The E/A wave ratio (expression of diastolic function) decreased
      at 60 mo compared with both 12 mo and baseline. CONCLUSIONS: In adults with
      lifetime congenital IGHD, the increase in carotid IMT elicited by GHRT was
      transitory and returned to baseline 5 years after therapy discontinuation.
      Despite this, the number of subjects with plaques remained stable at 60 mo and
      higher than at baseline.

PMID- 22416079
TI  - Minireview: human ovarian cancer: biology, current management, and paths to
      personalizing therapy.
AB  - More than 90% of ovarian cancers have been thought to arise from epithelial cells
      that cover the ovarian surface or, more frequently, line subserosal cysts. Recent
      studies suggest that histologically similar cancers can arise from the fimbriae
      of Fallopian tubes and from deposits of endometriosis. Different histotypes are
      observed that resemble epithelial cells from the normal Fallopian tube (serous),
      endometrium (endometrioid), cervical glands (mucinous), and vaginal rests (clear
      cell) and that share expression of relevant HOX genes which drive normal
      gynecological differentiation. Two groups of epithelial ovarian cancers have been
      distinguished: type I low-grade cancers that present in early stage, grow slowly,
      and resist conventional chemotherapy but may respond to hormonal manipulation;
      and type II high-grade cancers that are generally diagnosed in advanced stage and
      grow aggressively but respond to chemotherapy. Type I cancers have wild-type p53
      and BRCA1/2, but have frequent mutations of Ras and Raf as well as expression of
      IGFR and activation of the phosphatidylinositol-3-kinase (PI3K) pathway.
      Virtually all type II cancers have mutations of p53, and almost half have
      mutation or dysfunction of BRCA1/2, but other mutations are rare, and oncogenesis
      appears to be driven by amplification of several growth-regulatory genes that
      activate the Ras/MAPK and PI3K pathways. Cytoreductive surgery and combination
      chemotherapy with platinum compounds and taxanes have improved 5-yr survival, but
      less than 40% of all stages can be cured. Novel therapies are being developed
      that target high-grade serous cancer cells with PI3Kness or BRCAness as well as
      the tumor vasculature. Both in silico and animal models are needed that more
      closely resemble type I and type II cancers to facilitate the identification of
      novel targets and to predict response to combinations of new agents.

PMID- 22416080
TI  - Galectin-1 markedly reduces the incidence of resorptions in mice missing
      immunophilin FKBP52.
AB  - Progesterone (P(4)) signaling is critical for pregnancy. We previously showed
      that immunopilin FK506 binding protein (FKBP)52 serves as a cochaperone to
      optimize progesterone receptor (PR) function in the uterus, and its deficiency
      leads to P(4) resistance in a pregnancy stage-specific and genetic background
      dependent manner in mice. In particular, sc placement of SILASTIC implants
      carrying P(4) rescued implantation failure in CD1 Fkbp52(-/-) mice, but the
      resorption rate was substantially high at midgestation due to reduced P(4)
      responsiveness. Because downstream targets of P(4)-FKBP52-PR signaling in the
      uterus to support pregnancy are not clearly understood, we performed proteomic
      analysis using Fkbp52(-/-), PR-deficient (Pgr(-/-)), and wild-type (WT) uteri. We
      found that the expression of galectin-1 (Gal1), an evolutionarily conserved
      glycan-binding protein, was significantly down-regulated in both Fkbp52(-/-) and
      Pgr(-/-) uteri compared with WT uteri. During early gestation, Lgals1, which
      encodes Gal1, was distinctly expressed in stromal and decidual cells. Lgals1
      expression was much lower in d 4 Fkbp52(-/-) uteri compared with WT uteri, and
      this reduction was reversed by P(4) supplementation. More interestingly,
      concomitant supplementation of recombinant Gal1 significantly suppressed the high
      resorption rate and leukocyte infiltration at implantation sites in CD1 Fkbp52(-/
      ) females carrying P(4) SILASTIC implants. These findings suggest that uterine
      Gal1 is an important downstream target of P(4)-FKBP52-PR signaling in the uterus
      to support P(4) responsiveness during pregnancy.

PMID- 22416081
TI  - Growth hormone-induced JAK2 signaling and GH receptor down-regulation: role of GH
      receptor intracellular domain tyrosine residues.
AB  - GH receptor (GHR) mediates important somatogenic and metabolic effects of GH. A
      thorough understanding of GH action requires intimate knowledge of GHR activation
      mechanisms, as well as determinants of GH-induced receptor down-regulation. We
      previously demonstrated that a GHR mutant in which all intracellular tyrosine
      residues were changed to phenylalanine was defective in its ability to activate
      signal transducer and activator of transcription (STAT)5 and deficient in GH
      induced down-regulation, but able to allow GH-induced Janus family of tyrosine
      kinase 2 (JAK2) activation. We now further characterize the signaling and
      trafficking characteristics of this receptor mutant. We find that the mutant
      receptor's extracellular domain conformation and its interaction with GH are
      indistinguishable from the wild-type receptor. Yet the mutant differs greatly
      from the wild-type in that GH-induced JAK2 activation is augmented and far more
      persistent in cells bearing the mutant receptor. Notably, unlike STAT5 tyrosine
      phosphorylation, GH-induced STAT1 tyrosine phosphorylation is retained and
      augmented in mutant GHR-expressing cells. The defective receptor down-regulation
      and persistent JAK2 activation of the mutant receptor do not depend on the
      sustained presence of GH or on the cell's ability to carry out new protein
      synthesis. Mutant receptors that exhibit resistance to GH-induced down-regulation
      are enriched in the disulfide-linked form of the receptor, which reflects the
      receptor's activated conformation. Furthermore, acute GH-induced internalization,
      a proximal step in down-regulation, is markedly impaired in the mutant receptor
      compared to the wild-type receptor. These findings are discussed in the context
      of determinants and mechanisms of regulation of GHR down-regulation.

PMID- 22416082
TI  - Glucagon-like peptide-2 directly regulates hypothalamic neurons expressing
      neuropeptides linked to appetite control in vivo and in vitro.
AB  - Glucagon-like peptide-2 (GLP-2), a proglucagon-derived peptide, has been
      postulated to affect appetite at the level of the hypothalamus. To gain better
      insight into this process, a degradation-resistant GLP-2 analog, human
      (Gly(2))GLP-2(1-33) [h(Gly(2))GLP-2] was intracerebroventricularly injected into
      mice to examine its action on food and water intake and also activation of
      hypothalamic anorexigenic alpha-melanocyte-stimulating
      hormone/proopiomelanocortin, neurotensin, and orexigenic neuropeptide Y, and
      ghrelin neurons. Central h(Gly(2))GLP-2 administration significantly suppressed
      food and water intake with acute weight loss at 2 h. Further, central
      h(Gly(2))GLP-2 robustly induced c-Fos activation in the hypothalamic arcuate,
      dorsomedial, ventromedial, paraventricular, and the lateral hypothalamic nuclei.
      We found differential colocalization of neuropeptides with c-Fos in specific
      regions of the hypothalamus. To assess whether hypothalamic neuropeptides are
      directly regulated by GLP-2 in vitro, we used an adult-derived clonal,
      immortalized hypothalamic cell line, mHypoA-2/30, that endogenously expresses
      functional GLP-2 receptors (GLP-2R) and two of the feeding-related neuropeptides
      linked to GLP-2R activation in vivo: neurotensin and ghrelin. Treatment with
      h(Gly(2))GLP-2 stimulated c-Fos expression and phosphorylation of cAMP response
      element-binding protein/activating transcription factor-1. In addition, treatment
      with h(Gly(2))GLP-2 significantly increased neurotensin and ghrelin mRNA
      transcript levels by 50 and 95%, respectively, at 24 h after treatment in protein
      kinase A-dependent manner. Taken together, these findings implicate the protein
      kinase A pathway as the means by which GLP-2 can up-regulate hypothalamic
      neuropeptide mRNA levels and provide evidence for a link between central GLP-2R
      activation and specific hypothalamic neuropeptides involved in appetite
      regulation.

PMID- 22416083
TI  - Resting energy expenditure and energetic cost of feeding are augmented after Roux
      en-Y gastric bypass in obese mice.
AB  - Although the prevalence of obesity has increased dramatically throughout the
      world during the last 25 yr, its long-term control remains poor. Currently, only
      gastrointestinal weight loss surgery, especially Roux-en-Y gastric bypass (RYGB),
      is associated with substantial and sustained weight loss and resolution or
      significant improvement of diabetes mellitus and other metabolic obesity-induced
      complications. Clinical observations and recent studies have suggested that RYGB
      induces its effects by changing the physiology of weight regulation.
      Understanding the underlying mechanisms of these profound and sustainable effects
      could facilitate the development of novel and less invasive treatments against
      obesity and its complications. To study the physiological mechanisms of RYGB, we
      have developed a mouse RYGB model that replicates the human operation. The aims
      of this study were to develop a roadmap for assessing energy expenditure (EE) in
      animal models of weight loss surgery and to examine the effects of RYGB on EE. We
      first measured EE by indirect calorimetry in groups of animals that underwent
      RYGB or a sham operation. Calorimetry data were analyzed using three different
      methods: normalization by total body mass, allometric scaling, and analysis of
      covariance modeling. RYGB in mice induced a significant increase in EE that was
      independent of the method used. An energy balance analysis was then performed,
      which also confirmed that RYGB-treated animals have higher energy maintenance
      needs. Finally, we determined the EE components that account for the observed
      increase in EE, and we found that resting EE and postprandial thermogenesis are
      the major contributors to this increase.

PMID- 22416084
TI  - Estrogen receptors alpha and beta have different gender-dependent effects on the
      adaptive responses to load bearing in cancellous and cortical bone.
AB  - To determine the effect of estrogen receptors (ER) alpha and beta on bones'
      adaptive response to loading, we subjected the right tibiae of mice lacking
      ERalpha or ERbeta activity to either axial loading or to disuse. Adaptive changes
      in architecture were assessed by comparing differences between the right
      (treated) and left (control) tibiae in these genotypes as assessed by
      microcomputed tomography. In female ERalpha(-/-) mice, the net-osteogenic
      response to loading was lower in cortical bone compared with their wild-type
      littermates (11.2 vs. 20.9% in ERalpha(+/+)), but it was higher in both cortical
      and cancellous bone of male ERalpha(-/-) mice (cortical 20.0 vs. 4.6% in
      ERalpha(+/+); cancellous 30.0 vs. 5.3% in ERalpha(+/+), P < 0.05). In ERbeta(-/-)
      male and female mice, the net-osteogenic response to loading was higher in
      cortical bone (males 10.9 vs. 3.9% in ERbeta(+/+); females 18.5 vs. 15.8% in
      ERbeta(+/+), P < 0.05) but no different from controls in cancellous bone. The
      bone loss in response to disuse was less in cancellous bone of ERalpha(-/-) mice
      than in controls (-15.9 vs. -21.3%, respectively, P < 0.05) but no different at
      any other site or between any other groups. Our conclusion is that functional
      ERalpha enhances the net-osteogenic response to loading in cortical but not
      cancellous bone in female mice but reduces it in males. ERbeta decreases the
      response to loading in cortical bone of males and females but has no effect in
      cancellous bone. Bone loss due to disuse in cortical bone is unaffected by ER
      status, but in cancellous bone, functional ERalpha contributes to greater disuse
      related bone loss.

PMID- 22416085
TI  - Differential actions of prolactin on electrical activity and intracellular signal
      transduction in hypothalamic neurons.
AB  - In many tissues, including brain, prolactin action is predominantly mediated by
      the Janus kinase/signal transducer and activator of transcription (STAT) signal
      transduction pathway, leading to changes in gene transcription. However,
      prolactin can also exert rapid actions on electrical activity of hypothalamic
      neurons. Here, we investigate whether both responses occur in a single cell type,
      focusing on three specific populations known to be influenced by prolactin: GnRH
      neurons, tuberoinfundibular dopamine (TIDA) neurons, and neurons in the
      anteroventral-periventricular nucleus in female mice. We performed phosphorylated
      STAT5 (pSTAT5) immunohistochemistry to identify prolactin-responsive neurons
      after in vivo prolactin treatment. In addition, we carried out in vitro
      electrophysiology in slices from transgenic mice expressing green fluorescent
      protein driven by the GnRH or tyrosine hydroxylase promoters as well as from
      C57BL/6J mice to assess acute electrical responses to prolactin. Approximately
      88% of TIDA neurons expressed pSTAT5 in diestrous mice, rising to 97% after
      prolactin treatment. All TIDA neurons also showed a rapid increase in firing rate
      after prolactin treatment. In contrast, very few GnRH neurons (11%) showed pSTAT5
      in response to prolactin, and none showed a change in electrical activity.
      Finally, in the anteroventral-periventricular nucleus, most neurons (69%)
      responded to prolactin treatment with an increase in pSTAT5, but only 2/38 (~5%)
      showed changes in electrical activity in response to prolactin. These
      observations show that prolactin recruits different combinations of electrical
      and transcriptional responses in neurons depending upon their anatomical location
      and phenotype. This may be critical in establishing appropriate responses to
      prolactin under different physiological conditions.

PMID- 22416086
TI  - Screening to prevent heart failure (STOP-HF): expanding the focus beyond
      asymptomatic left ventricular systolic dysfunction.
AB  - AIMS: We evaluated the extent to which left ventricular diastolic dysfunction
      (LVDD) contributes to the high false-positive rates observed when natriuretic
      peptides (NPs) are used to screen for left ventricular systolic dysfunction
      (LVSD), and the use of NPs in combination with electrocardiogram (ECG) to screen
      for pre-clinical ventricular dysfunction (PCVD). METHODS AND RESULTS: Eight
      hundred and fourteen patients over 40 years of age and with at least one
      cardiovascular risk factor were recruited. Screening strategies for LVSD included
      brain natriuretic peptide (BNP) alone at cut-offs of 20, 50, and 100 pg/mL, and
      BNP and abnormal ECG combined. Systolic and diastolic function was assessed by
      Doppler echocardiography. A left ventricular ejection fraction (LVEF) of <50% was
      present in 33 (4.1%) of subjects, while 11 (1.4%) had LVEF <40%. At a cut-off of
      20, 50, and 100 pg/mL, sensitivity for BNP alone when screening for LVSD was 88,
      70, and 45%, and specificity 46, 77, and 90%, respectively. Of those labelled
      'false positive' in the 20, 50, and 100 pg/mL cut-off groups, 26, 46, and 65%,
      respectively, were found to have significant LVDD (left atrial volume index >34
      mL/m(2)). Optimal sensitivity (80%) and specificity (72%) for PCVD was obtained
      when BNP at a cut-off of 50 pg/mL or an abnormal ECG were defined as a positive
      screen so that only this group would be sent for Doppler echocardiography.
      CONCLUSIONS: A significant number of patients at risk for LVSD and labelled false
      positive with screening were found to have LVDD. Identifying this at-risk cohort
      may improve outcomes, but the clinical and economic benefit of this screening
      strategy requires formal assessment.

PMID- 22416087
TI  - The cover. Farmhouse.

PMID- 22416088
TI  - International debate erupts over research on potentially dangerous bird flu
      strains.

PMID- 22416089
TI  - Study raises concerns about "heading" in soccer, but jury is still out on risks.

PMID- 22416090
TI  - Reflux drugs linked to C. difficile-related diarrhea.

PMID- 22416091
TI  - Intracoronary bone marrow mononuclear cells after myocardial infarction.

PMID- 22416092
TI  - Intracoronary bone marrow mononuclear cells after myocardial infarction.

PMID- 22416093
TI  - Clopidogrel dosing based on genotype.

PMID- 22416094
TI  - Reticulated white lip.

PMID- 22416095
TI  - National trends in ambulance use by patients with stroke, 1997-2008.

PMID- 22416096
TI  - Can genomics bend the cost curve?

PMID- 22416097
TI  - Preventing depression: a global priority.

PMID- 22416098
TI  - A piece of my mind. Underestimating the value of reassurance.

PMID- 22416099
TI  - Association of hospital spending intensity with mortality and readmission rates
      in Ontario hospitals.
AB  - CONTEXT: The extent to which better spending produces higher-quality care and
      better patient outcomes in a universal health care system with selective access
      to medical technology is unknown. OBJECTIVE: To assess whether acute care
      patients admitted to higher-spending hospitals have lower mortality and
      readmissions. DESIGN, SETTING, AND PATIENTS: The study population comprised
      adults (>18 years) in Ontario, Canada, with a first admission for acute
      myocardial infarction (AMI) (n = 179,139), congestive heart failure (CHF) (n =
      92,377), hip fracture (n = 90,046), or colon cancer (n = 26,195) during 1998
      2008, with follow-up to 1 year. The exposure measure was the index hospital's end
      of-life expenditure index for hospital, physician, and emergency department
      services. MAIN OUTCOME MEASURES: The primary outcomes were 30-day and 1-year
      mortality and readmissions and major cardiac events (readmissions for AMI,
      angina, CHF, or death) for AMI and CHF. RESULTS: Patients' baseline health status
      was similar across hospital expenditure groups. Patients admitted to hospitals in
      the highest- vs lowest-spending intensity terciles had lower rates of all adverse
      outcomes. In the highest- vs lowest-spending hospitals, respectively, the age-
      and sex-adjusted 30-day mortality rate was 12.7% vs 12.8% for AMI, 10.2% vs 12.4%
      for CHF, 7.7% vs 9.7% for hip fracture, and 3.3% vs 3.9% for CHF; fully adjusted
      relative 30-day mortality rates were 0.93 (95% CI, 0.89-0.98) for AMI, 0.81 (95%
      CI, 0.76-0.86) for CHF, 0.74 (95% CI, 0.68-0.80) for hip fracture, and 0.78 (95%
      CI, 0.66-0.91) for colon cancer. Results for 1-year mortality, readmissions, and
      major cardiac events were similar. Higher-spending hospitals had higher nursing
      staff ratios, and their patients received more inpatient medical specialist
      visits, interventional (AMI cohort) and medical (AMI and CHF cohorts) cardiac
      therapies, preoperative specialty care (colon cancer cohort), and postdischarge
      collaborative care with a cardiologist and primary care physician (AMI and CHF
      cohorts). CONCLUSION: Among Ontario hospitals, higher spending intensity was
      associated with lower mortality, readmissions, and cardiac event rates.

PMID- 22416100
TI  - Association between azithromycin therapy and duration of bacterial shedding among
      patients with Shiga toxin-producing enteroaggregative Escherichia coli O104:H4.
AB  - CONTEXT: An outbreak of Shiga toxin-producing enteroaggregative Escherichia coli
      (STEC O104:H4) infection with a high incidence of hemolytic uremic syndrome (HUS)
      occurred in Germany in May 2011. Antibiotic treatment of STEC infection is
      discouraged because it might increase the risk of HUS development. However,
      antibiotic therapy is widely used to treat enteroaggregative E coli infection. In
      the German outbreak, a substantial number of patients received prophylactic
      azithromycin treatment as part of a therapeutic regimen with the C5 antibody
      eculizumab. OBJECTIVE: To analyze the duration of bacterial shedding in patients
      with STEC infection who did and did not receive oral azithromycin therapy.
      DESIGN, SETTING, AND PATIENTS: At a single center in Lubeck, Germany, 65 patients
      with STEC infection, including patients with HUS as well as STEC-infected
      outpatients without manifestation of HUS, were investigated between May 15 and
      July 26, 2011, and were monitored for a mean of 39.3 days after onset of clinical
      symptoms. MAIN OUTCOME MEASURE: Carriage of STEC after azithromycin therapy.
      RESULTS: Twenty-two patients received oral azithromycin and 43 patients did not
      receive antibiotic treatment. Among antibiotic-treated patients, long-term STEC
      carriage (>28 days) was observed in 1 of 22 patients (4.5%; 95% CI, 0%-13.3%)
      compared with 35 of 43 patients (81.4%; 95% CI, 69.8%-93.0%) who were not treated
      with antibiotics (P < .001). All 22 patients receiving azithromycin treatment had
      at least 3 STEC-negative stool specimens after the completion of treatment, and
      no recurrence of STEC was observed in these patients. As proof of principle, 15
      patients who initially were not treated with antibiotics and were long-term STEC
      carriers were treated with oral azithromycin given for 3 days and subsequently
      had negative stool specimens. CONCLUSION: Treatment with azithromycin was
      associated with a lower frequency of long-term STEC O104:H4 carriage.

PMID- 22416101
TI  - Endoscopic transgastric vs surgical necrosectomy for infected necrotizing
      pancreatitis: a randomized trial.
AB  - CONTEXT: Most patients with infected necrotizing pancreatitis require
      necrosectomy. Surgical necrosectomy induces a proinflammatory response and is
      associated with a high complication rate. Endoscopic transgastric necrosectomy, a
      form of natural orifice transluminal endoscopic surgery, may reduce the
      proinflammatory response and reduce complications. OBJECTIVE: To compare the
      proinflammatory response and clinical outcome of endoscopic transgastric and
      surgical necrosectomy. DESIGN, SETTING, AND PATIENTS: Randomized controlled
      assessor-blinded clinical trial in 3 academic hospitals and 1 regional teaching
      hospital in The Netherlands between August 20, 2008, and March 3, 2010. Patients
      had signs of infected necrotizing pancreatitis and an indication for
      intervention. INTERVENTIONS: Random allocation to endoscopic transgastric or
      surgical necrosectomy. Endoscopic necrosectomy consisted of transgastric
      puncture, balloon dilatation, retroperitoneal drainage, and necrosectomy.
      Surgical necrosectomy consisted of video-assisted retroperitoneal debridement or,
      if not feasible, laparotomy. MAIN OUTCOME MEASURES: The primary end point was the
      postprocedural proinflammatory response as measured by serum interleukin 6 (IL-6)
      levels. Secondary clinical end points included a predefined composite end point
      of major complications (new-onset multiple organ failure, intra-abdominal
      bleeding, enterocutaneous fistula, or pancreatic fistula) or death. RESULTS: We
      randomized 22 patients, 2 of whom did not undergo necrosectomy following
      percutaneous catheter drainage and could not be analyzed for the primary end
      point. Endoscopic transgastric necrosectomy reduced the postprocedural IL-6
      levels compared with surgical necrosectomy (P = .004). The composite clinical end
      point occurred less often after endoscopic necrosectomy (20% vs 80%; risk
      difference [RD], 0.60; 95% CI, 0.16-0.80; P = .03). Endoscopic necrosectomy did
      not cause new-onset multiple organ failure (0% vs 50%, RD, 0.50; 95% CI, 0.12
      0.76; P = .03) and reduced the number of pancreatic fistulas (10% vs 70%; RD,
      0.60; 95% CI, 0.17-0.81; P = .02). CONCLUSION: In patients with infected
      necrotizing pancreatitis, endoscopic necrosectomy reduced the proinflammatory
      response as well as the composite clinical end point compared with surgical
      necrosectomy. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN07091918.

PMID- 22416103
TI  - Does this patient have a severe upper gastrointestinal bleed?
AB  - CONTEXT: Emergency physicians must determine both the location and the severity
      of acute gastrointestinal bleeding (GIB) to optimize the diagnostic and
      therapeutic approaches. OBJECTIVES: To identify the historical features,
      symptoms, signs, bedside maneuvers, and basic laboratory test results that
      distinguish acute upper GIB (UGIB) from acute lower GIB (LGIB) and to risk
      stratify those patients with a UGIB least likely to have severe bleeding that
      necessitates an urgent intervention. DATA SOURCES: A structured search of MEDLINE
      (1966-September 2011) and reference lists from retrieved articles, review
      articles, and physical examination textbooks. STUDY SELECTION: High-quality
      studies were included of adult patients who were either admitted with GIB or
      evaluated in emergency departments with bedside evaluations and/or routine
      laboratory tests, and studies that did not include endoscopic findings in
      prediction models. The initial search yielded 2628 citations, of which 8 were
      retained that tested methods of identifying a UGIB and 18 that identified methods
      of determining the severity of UGIB. DATA EXTRACTION: One author abstracted the
      data (prevalence, sensitivity, specificity, and likelihood ratios [LRs]) and
      assessed methodological quality, with confirmation by another author. Data were
      combined using random effects measures. DATA SYNTHESIS: The majority of patients
      (N = 1776) had an acute UGIB (prevalence, 63%; 95% CI, 51%-73%). Several clinical
      factors increase the likelihood that a patient has a UGIB, including a patient
      reported history of melena (LR range, 5.1-5.9), melenic stool on examination (LR,
      25; 95% CI, 4-174), a nasogastric lavage with blood or coffee grounds (LR, 9.6;
      95% CI, 4.0-23.0), and a serum urea nitrogen:creatinine ratio of more than 30
      (summary LR, 7.5; 95% CI, 2.8-12.0). Conversely, the presence of blood clots in
      stool (LR, 0.05; 95% CI, 0.01-0.38) decreases the likelihood of a UGIB. Of the
      patients clinically diagnosed with acute UGIB, 36% (95% CI, 29%-44%) had severe
      bleeding. A nasogastric lavage with red blood (summary LR, 3.1; 95% CI, 1.2
      14.0), tachycardia (LR, 4.9; 95% CI, 3.2-7.6), or a hemoglobin level of less than
      8 g/dL (LR range, 4.5-6.2) increase the likelihood of a severe UGIB requiring
      urgent intervention. A Blatchford score of 0 (summary LR, 0.02; 95% CI, 0-0.05)
      decreases the likelihood that a UGIB requires urgent intervention. CONCLUSIONS:
      Melena, nasogastric lavage with blood or coffee grounds, or serum urea
      nitrogen:creatinine ratio of more than 30 increase the likelihood of a UGIB.
      Blood clots in the stool make a UGIB much less likely. The Blatchford clinical
      prediction score, which does not require nasogastric lavage, is very efficient
      for identifying patients who do not require urgent intervention.

PMID- 22416102
TI  - Association of age at diagnosis and genetic mutations in patients with
      neuroblastoma.
AB  - CONTEXT: Neuroblastoma is diagnosed over a wide age range from birth through
      young adulthood, and older age at diagnosis is associated with a decline in
      survivability. OBJECTIVE: To identify genetic mutations that are associated with
      age at diagnosis in patients with metastatic neuroblastoma. DESIGN, SETTING, AND
      PATIENTS: Whole genome sequencing was performed on DNA from diagnostic tumors and
      their matched germlines from 40 patients with metastatic neuroblastoma obtained
      between 1987 and 2009. Age groups at diagnosis included infants (0-<18 months),
      children (18 months-<12 years), and adolescents and young adults (>=12 years). To
      confirm the findings from this discovery cohort, validation testing using tumors
      from an additional 64 patients obtained between 1985 and 2009 also was performed.
      Formalin-fixed, paraffin-embedded tumor tissue was used for immunohistochemistry
      and fluorescence in situ hybridization. Telomere lengths were analyzed using
      whole genome sequencing data, quantitative polymerase chain reaction, and
      fluorescent in situ hybridization. MAIN OUTCOME MEASURE: Somatic recurrent
      mutations in tumors from patients with neuroblastoma correlated with the age at
      diagnosis and telomere length. RESULTS: In the discovery cohort (n = 40),
      mutations in the ATRX gene were identified in 100% (95% CI, 50%-100%) of tumors
      from patients in the adolescent and young adult group (5 of 5), in 17% (95% CI,
      7%-36%) of tumors from children (5 of 29), and 0% (95% CI, 0%-40%) of tumors from
      infants (0 of 6). In the validation cohort (n = 64), mutations in the ATRX gene
      were identified in 33% (95% CI, 17%-54%) of tumors from patients in the
      adolescent and young adult group (9 of 27), in 16% (95% CI, 6%-35%) of tumors
      from children (4 of 25), and in 0% (95% CI, 0%-24%) of tumors from infants (0 of
      12). In both cohorts (N = 104), mutations in the ATRX gene were identified in 44%
      (95% CI, 28%-62%) of tumors from patients in the adolescent and young adult group
      (14 of 32), in 17% (95% CI, 9%-29%) of tumors from children (9 of 54), and in 0%
      (95% CI, 0%-17%) of tumors from infants (0 of 18). ATRX mutations were associated
      with an absence of the ATRX protein in the nucleus and with long telomeres.
      CONCLUSION: ATRX mutations were associated with age at diagnosis in children and
      young adults with stage 4 neuroblastoma. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00588068.

PMID- 22416104
TI  - Appearance of a rapidly expanding facial eschar in a severely injured trauma
      patient.

PMID- 22416105
TI  - The relationship between cost and quality: no free lunch.

PMID- 22416106
TI  - Endoscopic transgastric necrosectomy for infected necrotizing pancreatitis.

PMID- 22416108
TI  - JAMA patient page. Hemolytic uremic syndrome.

PMID- 22416109
TI  - Dynamic imaging response following radiation therapy predicts long-term outcomes
      for diffuse low-grade gliomas.
AB  - Quantitative imaging assessment of radiation therapy (RT) for diffuse low-grade
      gliomas (DLGG) by measuring the velocity of diametric expansion (VDE) over time
      has never been studied. We assessed the VDE changes following RT and determined
      whether this parameter can serve as a prognostic factor. We reviewed a
      consecutive series of 33 adults with supratentorial DLGG treated with first-line
      RT with available imaging follow-up (median follow-up, 103 months). Before RT,
      all patients presented with a spontaneous tumor volume increase (positive VDE,
      mean 5.9 mm/year). After RT, all patients demonstrated a tumor volume decrease
      (negative VDE, mean, -16.7 mm/year) during a mean 49-month duration. In
      univariate analysis, initial tumor volume (>100 cm(3)), lack of IDH1 expression,
      p53 expression, high proliferation index, and fast post-RT tumor volume decrease
      (VDE at -10 mm/year or faster, fast responders) were associated with a
      significantly shorter overall survival (OS). The median OS was significantly
      longer (120.8 months) for slow responders (post-RT VDE slower than -10.0 mm/year)
      than for fast responders (47.9 months). In multivariate analysis, fast
      responders, larger initial tumor volume, lack of IDH1 expression, and p53
      expression were independent poor prognostic factors for OS. A high proliferation
      index was significantly more frequent in the fast responder subgroup than in the
      slow responder subgroup. We conclude that the pattern of post-RT VDE changes is
      an independent prognostic factor for DLGG and offers a quantitative parameter to
      predict long-term outcomes. We propose to monitor individually the post-RT VDE
      changes using MRI follow-up, with particular attention to fast responders.

PMID- 22416111
TI  - Angioarchitectural features associated with hemorrhagic presentation in pediatric
      cerebral arteriovenous malformations.
AB  - BACKGROUND AND OBJECTIVE: To date, there have been few published studies
      examining the relationship between arteriovenous malformation (AVM)
      angioarchitecture and hemorrhagic presentation among children with cerebral AVMs.
      This study examines this relationship in this unique population, in whom
      symptomatic presentation of cerebral AVM is the norm rather than the exception.
      METHODS: A cohort of children with AVMs from 2000 to 2011 were included.
      Predictors studied included patient age, gender and angioarchitectural features,
      including AVM location, nidus size and morphology, venous drainage, presence of
      venous outflow lesions and associated aneurysms. Predictors of hemorrhagic
      presentation were assessed using multivariate logistic regression. RESULTS: 135
      children (70 males, mean age 10.1 years) were included. 86/135 (63.7%) children
      presented with hemorrhage, 18 (13.3%) with seizures, 17 (12.6%) with headaches or
      neurological deficits and 14 (10.4%) were asymptomatic. AVM location, morphology
      and the presence of associated aneurysm, venous ectasia, draining vein stenosis
      and single draining vein were not significantly associated factors. After
      multivariate analysis, AVM size (OR 0.57, 95% CI 0.43 to 0.77; p<0.01), exclusive
      deep venous drainage (OR 4.94, 95% CI 1.30 to 18.8; p=0.02) and infratentorial
      location (OR 9.94, 95% CI 1.71 to 51.76; p=0.01) were independently associated
      with hemorrhagic presentation. CONCLUSION: Smaller AVM size, exclusive deep
      venous drainage and infratentorial location are specific angioarchitectural
      factors independently associated with initial hemorrhagic presentation in
      children with AVMs.

PMID- 22416112
TI  - Initial experience with distal guide catheter placement in the treatment of
      cerebrovascular disease: clinical safety and efficacy.
AB  - BACKGROUND: Advancements in technology have created a current generation of guide
      catheters that not only provide stable access but also allow navigation of
      tortuous portions of the carotid siphon facilitating more distal access. Clinical
      experience since the release of the current generation of guide catheters was
      reviewed to determine their safety and efficacy. METHODS: Between October 2007
      and November 2011, all neurointerventional procedures requiring access to the
      intracranial arterial circulation performed at our institution were reviewed.
      Clinical performance and complication rates of current generation guide catheters
      were compared with conventional guide catheters. RESULTS: 1188
      neurointerventional procedures were performed, of which 659 were eligible for
      this study. When navigating the anterior circulation, intracranial purchase was
      achieved significantly more often with current generation 0.070 inch and 0.053
      inch guide catheters compared with conventional guide catheters. Similarly,
      current generation 0.070 inch and 0.053 inch catheters navigated at least one
      sharp 90 degrees  turn significantly more often than conventional guide
      catheters. Guide catheter related complications were encountered in 1.4% of cases
      with both catheter generations and differences were not significant although more
      complications were found when guide catheter tip position was cervical rather
      than intracranial. CONCLUSION: Current generation guide catheters allow distal
      access with a high rate of success while maintaining a low rate of complications.
      When intracranial location of the guide catheter was obtained, fewer
      complications occurred.

PMID- 22416113
TI  - A qualitative examination of the positive and negative consequences associated
      with going tobacco-free in substance abuse treatment: the NY State experience.
AB  - INTRODUCTION: In 2008, the New York State (NYS) Office of Alcoholism and
      Substance Abuse Services (OASAS) required all state-funded or state-certified
      addiction treatment programs to be 100% tobacco-free. The regulation prohibits
      the use or possession of all tobacco products by patients, employees, volunteers,
      and visitors. This includes exterior grounds and vehicles owned, leased, or
      operated by the facility. Addiction treatment centers are also required to screen
      patients for tobacco use and incorporate tobacco cessation into treatment
      programming. This study examined the perceived effectiveness of this regulation
      from the perspective of counselors and clinical supervisors. METHODS: Qualitative
      data were collected from 261 counselors and 80 clinical supervisors working in 50
      free-standing substance abuse treatment programs throughout NYS. Questions asked
      about the perceived positive and negative consequences of the OASAS regulation
      approximately 1 year after its implementation. RESULTS: The findings indicate
      mixed reactions to the regulation. A wide range of positive and negative
      consequences were identified, which were generally consistent across counselor
      and clinical supervisor reports. The most commonly reported positive outcomes
      were positive behavior change (e.g., less smoking, increased intentions to quit)
      and increased awareness about smoking (e.g., dangers, available assistance to
      quit). The most commonly reported negative consequences were reinforcing addict
      behaviors among patients (e.g., lying, "dealing" cigarettes) and enforcement
      problems (e.g., difficulty enforcing, policing for compliance). CONCLUSION:
      Findings have implications for the implementation of tobacco-free regulations in
      substance abuse treatment programs.

PMID- 22416114
TI  - Association between willingness to use snus to quit smoking and perception of
      relative risk between snus and cigarettes.
AB  - INTRODUCTION: Smokers are often incorrect in their assessment of the relative
      risk of snus and cigarettes. We have studied how perception of risks of snus
      compared with cigarettes was associated with the willingness of trying snus as a
      quit-smoking method. METHODS: Fourteen thousand seven hundred and forty-four
      Norwegian men aged 20-50 years were selected at random from a national
      representative web panel and sent a questionnaire by e-mail. Of the 7,170 (48.6%)
      who responded, there were 1,155 former daily smokers who reported method for
      quitting smoking and 1,213 current daily smokers who stated their willingness to
      try different methods for quitting smoking. They were also asked to assess the
      relative risk between daily use of snus and cigarettes. RESULTS: Adjusted odds
      ratio (AOR) for reporting willingness to try snus in future quit attempts was
      significantly higher (AOR = 4.82, p < .001) for the 22.9% of the current smokers
      who, consistent with scientific evidence, believed that the health risks were
      "far lower" for snus than for cigarettes compared with the 39.8% who incorrectly
      perceived the health risks to be "equal or higher" for snus (reference AOR = 1).
      About 37.2% of the daily smokers believed that the risk was "somewhat lower" for
      snus than for cigarettes and had a significantly higher AOR of reporting
      willingness to try snus (AOR = 2.31, p < .001) compared with the reference group.
      CONCLUSION: Devising a way to inform smokers about the risk continuum of tobacco
      products could be an important research priority in countries where snus is
      allowed to compete with cigarettes for market share.

PMID- 22416115
TI  - Smoking in response to negative mood in men versus women as a function of
      distress tolerance.
AB  - INTRODUCTION: Negative mood situations often increase smoking behavior and
      reward, effects that may be greater among women and smokers low in tolerance for
      distress. METHODS: Adult dependent smokers (N = 164; 86 men, 78 women) first
      completed measures of distress tolerance via self-report and by mirror-tracing
      and breath-holding tasks. They then participated in 2 virtually identical
      laboratory sessions, involving induction of negative versus neutral mood
      (control) via pictorial slides and music. They rated negative affect (NA) before
      and during mood induction and smoked their preferred brand ad libitum during the
      last 14 min of mood induction. Our aim was to examine mood effects on NA, smoking
      reward ("liking"), and smoking intake (puff volume and number) as a function of
      sex and distress tolerance. RESULTS: Negative mood induction increased NA, as
      planned, and smoking reward and intake compared with neutral mood. Increases in
      NA and puff volume due to negative mood were greater in women compared with men,
      as hypothesized, but no main effects of the self-report or behavioral distress
      tolerance measures were seen in responses to mood induction. However,
      unexpectedly, lower self-reported distress tolerance was associated with greater
      smoking intake due to negative (but not neutral) mood in men and generally due to
      neutral (but not negative) mood in women. CONCLUSIONS: Negative mood may increase
      smoking intake more in women compared with men. Yet, low distress tolerance may
      enhance smoking intake due to negative versus neutral mood differentially between
      women and men, suggesting that sex and distress tolerance may interact to
      influence smoking responses to negative mood.

PMID- 22416116
TI  - The decline of menthol cigarette smoking in Australia, 1980-2008.
AB  - INTRODUCTION: Concerns have been expressed that menthol cigarettes are highly
      conducive to uptake and hence function as "starter cigarettes" for adolescents.
      There is strong evidence for this in the United States. If menthol cigarettes are
      critical to uptake for some adolescents, they might be expected to remain popular
      among adolescents independent of promotional activity. We analyzed trends in the
      market share of menthol brands in Australia among both adolescents and adults to
      provide further insights into the determinants of menthol cigarette smoking.
      METHODS: We used the Australian Secondary Students Alcohol and Drug Survey (1984
      2008), the Smoking and Health Survey (1980-1998), and the International Tobacco
      Control Four Nations Survey (2002-2008) to estimate market share of brands.
      Measures were reported use of all menthol brands for adults and use of the Alpine
      brand for adolescents. RESULTS: Menthol smoking was much more popular among
      female smokers of all age groups in the early 1980s. During the 1980s and 1990s,
      use declined markedly in the 18-29 age groups, while remaining relatively stable
      among older smokers. Use of Alpine declined markedly among adolescents in the
      1980s and 1990s. However, during this period, Alpine remained more popular among
      experimenting than regular smokers. CONCLUSIONS: Both Alpine and other menthol
      brands are now primarily "older women's cigarettes" in Australia. The trends in
      declining popularity among younger smokers suggest that targeted marketing plays
      a major role in determining menthol brand market share. Alpine has played a role
      as a "starter" cigarette in Australia but that role has decreased markedly since
      the 1980s. Within the Australian context, "light/mild" brands may have taken over
      the role of easier-to-smoke cigarettes that attract experimenting smokers.

PMID- 22416117
TI  - Behavioral economic analysis of withdrawal- and cue-elicited craving for tobacco:
      an initial investigation.
AB  - INTRODUCTION: The role of craving in nicotine dependence remains controversial
      and may be a function of measurement challenges. The current study used
      behavioral economic approach to test the hypotheses that subjective craving from
      acute withdrawal and exposure to tobacco cues dynamically increases the relative
      value of cigarettes. METHODS: Using a 2 (1-hr/12-hr deprivation) * 2
      (neutral/tobacco cues) within-subjects design, 33 nicotine dependent adults
      completed 2 laboratory sessions. Assessment included subjective craving and
      behavioral economic indices of cigarette demand, namely Intensity (i.e.,
      cigarette consumption at zero cost), O(max) (i.e., maximum total expenditure),
      Breakpoint (i.e., highest acceptable price for cigarettes), P(max) (i.e., price
      at which consumption becomes sensitive to price), and elasticity (i.e., price
      sensitivity). Behavioral economic indices were generated using a Cigarette
      Purchase Task in which participants selected between cigarettes for a subsequent
      2-hr self-administration period and money. RESULTS: Main effects of deprivation
      and tobacco cues were present for subjective craving and multiple behavioral
      economic indices of cigarette demand. Interestingly, deprivation significantly
      increased Breakpoint (p <= .01) and P(max) (p <= .05) and had trend-level effects
      on Intensity and O(max) (p <= .10); whereas cues significantly reduced elasticity
      (p <= .01), reflecting lower sensitivity to increasing prices. Heterogeneous
      associations were evident among the motivational variables but with aggregations
      suggesting variably overlapping motivational channels. CONCLUSIONS: These
      findings further support a behavioral economic approach to craving and a
      multidimensional conception of acute motivation for addictive drugs.
      Methodological considerations, including potential order effects, and the need
      for further refinement of these findings are discussed.

PMID- 22416118
TI  - Mitochondrial pathway of apoptosis is ancestral in metazoans.
AB  - The mitochondrial pathway of apoptosis is the major mechanism of physiological
      cell death in vertebrates. In this pathway, proapoptotic members of the Bcl-2
      family cause mitochondrial outer membrane permeabilization (MOMP), allowing the
      release of cytochrome c, which interacts with Apaf-1 to trigger caspase
      activation and apoptosis. Despite conservation of Bcl-2, Apaf-1, and caspases in
      invertebrate phyla, the existence of the mitochondrial pathway in any
      invertebrate is, at best, controversial. Here we show that apoptosis in a
      lophotrochozoan, planaria (phylum Platyhelminthes), is associated with MOMP and
      that cytochrome c triggers caspase activation in cytosolic extracts from these
      animals. Further, planarian Bcl-2 family proteins can induce and/or regulate cell
      death in yeast and can replace Bcl-2 proteins in mammalian cells to regulate
      MOMP. These results suggest that the mitochondrial pathway of apoptosis in
      animals predates the emergence of the vertebrates but was lost in some lineages
      (e.g., nematodes). In further support of this hypothesis, we surveyed the ability
      of cytochrome c to trigger caspase activation in cytosolic extracts from a
      variety of organisms and found this effect in cytosolic extracts from
      invertebrate deuterostomes (phylum Echinodermata).

PMID- 22416119
TI  - Tomato immune receptor Ve1 recognizes effector of multiple fungal pathogens
      uncovered by genome and RNA sequencing.
AB  - Fungal plant pathogens secrete effector molecules to establish disease on their
      hosts, and plants in turn use immune receptors to try to intercept these
      effectors. The tomato immune receptor Ve1 governs resistance to race 1 strains of
      the soil-borne vascular wilt fungi Verticillium dahliae and Verticillium albo
      atrum, but the corresponding Verticillium effector remained unknown thus far. By
      high-throughput population genome sequencing, a single 50-Kb sequence stretch was
      identified that only occurs in race 1 strains, and subsequent transcriptome
      sequencing of Verticillium-infected Nicotiana benthamiana plants revealed only a
      single highly expressed ORF in this region, designated Ave1 (for Avirulence on
      Ve1 tomato). Functional analyses confirmed that Ave1 activates Ve1-mediated
      resistance and demonstrated that Ave1 markedly contributes to fungal virulence,
      not only on tomato but also on Arabidopsis. Interestingly, Ave1 is homologous to
      a widespread family of plant natriuretic peptides. Besides plants, homologous
      proteins were only found in the bacterial plant pathogen Xanthomonas axonopodis
      and the plant pathogenic fungi Colletotrichum higginsianum, Cercospora beticola,
      and Fusarium oxysporum f. sp. lycopersici. The distribution of Ave1 homologs,
      coincident with the presence of Ave1 within a flexible genomic region, strongly
      suggests that Verticillium acquired Ave1 from plants through horizontal gene
      transfer. Remarkably, by transient expression we show that also the Ave1 homologs
      from F. oxysporum and C. beticola can activate Ve1-mediated resistance. In line
      with this observation, Ve1 was found to mediate resistance toward F. oxysporum in
      tomato, showing that this immune receptor is involved in resistance against
      multiple fungal pathogens.

PMID- 22416120
TI  - Regulatory architecture determines optimal regulation of gene expression in
      metabolic pathways.
AB  - In response to environmental changes, the connections ("arrows") in gene
      regulatory networks determine which genes modulate their expression, but the
      quantitative parameters of the network ("the numbers on the arrows") are equally
      important in determining the resulting phenotype. What are the objectives and
      constraints by which evolution determines these parameters? We explore these
      issues by analyzing gene expression changes in a number of yeast metabolic
      pathways in response to nutrient depletion. We find that a striking pattern
      emerges that couples the regulatory architecture of the pathway to the gene
      expression response. In particular, we find that pathways controlled by the
      intermediate metabolite activation (IMA) architecture, in which an intermediate
      metabolite activates transcription of pathway genes, exhibit the following
      response: the enzyme immediately downstream of the regulatory metabolite is under
      the strongest transcriptional control, whereas the induction of the enzymes
      upstream of the regulatory intermediate is relatively weak. This pattern of
      responses is absent in pathways not controlled by an IMA architecture. The
      observation can be explained by the constraint imposed by the fundamental
      feedback structure of the network, which places downstream enzymes under a
      negative feedback loop and upstream ones under a positive feedback loop. This
      general design principle for transcriptional control of a metabolic pathway can
      be derived from a simple cost/benefit model of gene expression, in which the
      observed pattern is an optimal solution. Our results suggest that the parameters
      regulating metabolic enzyme expression are optimized by evolution, under the
      strong constraint of the underlying regulatory architecture.

PMID- 22416121
TI  - An over-oxidized form of superoxide dismutase found in sporadic amyotrophic
      lateral sclerosis with bulbar onset shares a toxic mechanism with mutant SOD1.
AB  - Recent studies suggest that Cu/Zn superoxide dismutase (SOD1) could be pathogenic
      in both familial and sporadic amyotrophic lateral sclerosis (ALS) through either
      inheritable or nonheritable modifications. The presence of a misfolded WT SOD1 in
      patients with sporadic ALS, along with the recently reported evidence that
      reducing SOD1 levels in astrocytes derived from sporadic patients inhibits
      astrocyte-mediated toxicity on motor neurons, suggest that WT SOD1 may acquire
      toxic properties similar to familial ALS-linked mutant SOD1, perhaps through
      posttranslational modifications. Using patients' lymphoblasts, we show here that
      indeed WT SOD1 is modified posttranslationally in sporadic ALS and is iper
      oxidized (i.e., above baseline oxidation levels) in a subset of patients with
      bulbar onset. Derivatization analysis of oxidized carbonyl compounds performed on
      immunoprecipitated SOD1 identified an iper-oxidized SOD1 that recapitulates
      mutant SOD1-like properties and damages mitochondria by forming a toxic complex
      with mitochondrial Bcl-2. This study conclusively demonstrates the existence of
      an iper-oxidized SOD1 with toxic properties in patient-derived cells and
      identifies a common SOD1-dependent toxicity between mutant SOD1-linked familial
      ALS and a subset of sporadic ALS, providing an opportunity to develop biomarkers
      to subclassify ALS and devise SOD1-based therapies that go beyond the small group
      of patients with mutant SOD1.

PMID- 22416123
TI  - Lateral gene transfer as a support for the tree of life.
AB  - Lateral gene transfer (LGT), the acquisition of genes from other species, is a
      major evolutionary force. However, its success as an adaptive process makes the
      reconstruction of the history of life an intricate puzzle: If no gene has
      remained unaffected during the course of life's evolution, how can one rely on
      molecular markers to reconstruct the relationships among species? Here, we take a
      completely different look at LGT and its impact for the reconstruction of the
      history of life. Rather than trying to remove the effect of LGT in phylogenies,
      and ignoring as a result most of the information of gene histories, we use an
      explicit phylogenetic model of gene transfer to reconcile gene histories with the
      tree of species. We studied 16 bacterial and archaeal phyla, representing a
      dataset of 12,000 gene families distributed in 336 genomes. Our results show
      that, in most phyla, LGT provides an abundant phylogenetic signal on the pattern
      of species diversification and that this signal is robust to the choice of gene
      families under study. We also find that LGT brings an abundant signal on the
      location of the root of species trees, which has been previously overlooked. Our
      results quantify the great variety of gene transfer rates among lineages of the
      tree of life and provide strong support for the "complexity hypothesis," which
      states that genes whose products participate to macromolecular protein complexes
      are relatively resistant to transfer.

PMID- 22416122
TI  - Common genetic variants in the PSCA gene influence gene expression and bladder
      cancer risk.
AB  - Genome-wide association studies have identified a SNP, rs2294008, on 8q24.3
      within the prostate stem cell antigen (PSCA) gene, as a risk factor for bladder
      cancer. To fine-map this region, we imputed 642 SNPs within 100 Kb of rs2294008
      in addition to 33 markers genotyped in one of the reported genome-wide
      association study in 8,652 subjects. A multivariable logistic regression model
      adjusted for rs2294008 revealed a unique signal, rs2978974 (r(2) = 0.02, D' =
      0.19 with rs2294008). In the combined analysis of 5,393 cases and 7,324 controls,
      we detected a per-allele odds ratio (OR) = 1.11 [95% confidence interval (CI) =
      1.06-1.17, P = 5.8 * 10(-5)] for rs2294008 and OR = 1.07 (95% CI = 1.02-1.13, P =
      9.7 * 10(-3)) for rs2978974. The effect was stronger in carriers of both risk
      variants (OR = 1.24, 95% CI = 1.08-1.41, P = 1.8 * 10(-3)) and there was a
      significant multiplicative interaction (P = 0.035) between these two SNPs, which
      requires replication in future studies. The T risk allele of rs2294008 was
      associated with increased PSCA mRNA expression in two sets of bladder tumor
      samples (n = 36, P = 0.0007 and n = 34, P = 0.0054) and in normal bladder samples
      (n = 35, P = 0.0155), but rs2978974 was not associated with PSCA expression. SNP
      rs2978974 is located 10 Kb upstream of rs2294008, within an alternative
      untranslated first exon of PSCA. The non-risk allele G of rs2978974 showed strong
      interaction with nuclear proteins from five cell lines tested, implying a
      regulatory function. In conclusion, a joint effect of two PSCA SNPs, rs2294008
      and rs2978974, suggests that both variants may be important for bladder cancer
      susceptibility, possibly through different mechanisms that influence the control
      of mRNA expression and interaction with regulatory factors.

PMID- 22416124
TI  - Eosinophil-derived leukotriene C4 signals via type 2 cysteinyl leukotriene
      receptor to promote skin fibrosis in a mouse model of atopic dermatitis.
AB  - Atopic dermatitis (AD) skin lesions exhibit epidermal and dermal thickening,
      eosinophil infiltration, and increased levels of the cysteinyl leukotriene (cys
      LT) leukotriene C(4) (LTC(4)). Epicutaneous sensitization with ovalbumin of WT
      mice but not DeltadblGATA mice, the latter of which lack eosinophils, caused skin
      thickening, collagen deposition, and increased mRNA expression of the cys-LT
      generating enzyme LTC(4) synthase (LTC(4)S). Skin thickening and collagen
      deposition were significantly reduced in ovalbumin-sensitized skin of LTC(4)S
      deficient and type 2 cys-LT receptor (CysLT(2)R)-deficient mice but not type 1
      cys-LT receptor (CysLT(1)R)-deficient mice. Adoptive transfer of bone marrow
      derived eosinophils from WT but not LTC(4)S-deficient mice restored skin
      thickening and collagen deposition in epicutaneous-sensitized skin of
      DeltadblGATA recipients. LTC(4) stimulation caused increased collagen synthesis
      by human skin fibroblasts, which was blocked by CysLT(2)R antagonism but not
      CysLT(1)R antagonism. Furthermore, LTC(4) stimulated skin fibroblasts to secrete
      factors that elicit keratinocyte proliferation. These findings establish a role
      for eosinophil-derived cys-LTs and the CysLT(2)R in the hyperkeratosis and
      fibrosis of allergic skin inflammation. Strategies that block eosinophil
      infiltration, cys-LT production, or the CysLT(2)R might be useful in the
      treatment of AD.

PMID- 22416125
TI  - Protein misinteraction avoidance causes highly expressed proteins to evolve
      slowly.
AB  - The tempo and mode of protein evolution have been central questions in biology.
      Genomic data have shown a strong influence of the expression level of a protein
      on its rate of sequence evolution (E-R anticorrelation), which is currently
      explained by the protein misfolding avoidance hypothesis. Here, we show that this
      hypothesis does not fully explain the E-R anticorrelation, especially for protein
      surface residues. We propose that natural selection against protein-protein
      misinteraction, which wastes functional molecules and is potentially toxic,
      constrains the evolution of surface residues. Because highly expressed proteins
      are under stronger pressures to avoid misinteraction, surface residues are
      expected to show an E-R anticorrelation. Our molecular-level evolutionary
      simulation and yeast genomic analysis confirm multiple predictions of the
      hypothesis. These findings show a pluralistic origin of the E-R anticorrelation
      and reveal the role of protein misinteraction, an inherent property of complex
      cellular systems, in constraining protein evolution.

PMID- 22416126
TI  - Structure of the heterodimer of human NONO and paraspeckle protein component 1
      and analysis of its role in subnuclear body formation.
AB  - Proteins of the Drosophila behavior/human splicing (DBHS) family include
      mammalian SFPQ (PSF), NONO (p54nrb), PSPC1, and invertebrate NONA and Hrp65. DBHS
      proteins are predominately nuclear, and are involved in transcriptional and
      posttranscriptional gene regulatory functions as well as DNA repair. DBHS
      proteins influence a wide gamut of biological processes, including the regulation
      of circadian rhythm, carcinogenesis, and progression of cancer. Additionally,
      mammalian DBHS proteins associate with the architectural long noncoding RNA NEAT1
      (Menepsilon/beta) to form paraspeckles, subnuclear bodies that alter gene
      expression via the nuclear retention of RNA. Here we describe the crystal
      structure of the heterodimer of the multidomain conserved region of the DBHS
      proteins, PSPC1 and NONO. These proteins form an extensively intertwined dimer,
      consistent with the observation that the different DBHS proteins are typically
      copurified from mammalian cells, and suggesting that they act as obligate
      heterodimers. The PSPC1/NONO heterodimer has a right-handed antiparallel coiled
      coil that positions two of four RNA recognition motif domains in an unprecedented
      arrangement on either side of a 20-A channel. This configuration is supported by
      a protein:protein interaction involving the NONA/paraspeckle domain, which is
      characteristic of the DBHS family. By examining various mutants and truncations
      in cell culture, we find that DBHS proteins require an additional antiparallel
      coiled-coil emanating from either end of the dimer for paraspeckle subnuclear
      body formation. These results suggest that paraspeckles may potentially form
      through self-association of DBHS dimers into higher-order structures.

PMID- 22416127
TI  - Rabbits are not resistant to prion infection.
AB  - The ability of prions to infect some species and not others is determined by the
      transmission barrier. This unexplained phenomenon has led to the belief that
      certain species were not susceptible to transmissible spongiform encephalopathies
      (TSEs) and therefore represented negligible risk to human health if consumed.
      Using the protein misfolding cyclic amplification (PMCA) technique, we were able
      to overcome the species barrier in rabbits, which have been classified as TSE
      resistant for four decades. Rabbit brain homogenate, either unseeded or seeded in
      vitro with disease-related prions obtained from different species, was subjected
      to serial rounds of PMCA. De novo rabbit prions produced in vitro from unseeded
      material were tested for infectivity in rabbits, with one of three
      intracerebrally challenged animals succumbing to disease at 766 d and displaying
      all of the characteristics of a TSE, thereby demonstrating that leporids are not
      resistant to prion infection. Material from the brain of the clinically affected
      rabbit containing abnormal prion protein resulted in a 100% attack rate after its
      inoculation in transgenic mice overexpressing rabbit PrP. Transmissibility to
      rabbits (>470 d) has been confirmed in 2 of 10 rabbits after intracerebral
      challenge. Despite rabbits no longer being able to be classified as resistant to
      TSEs, an outbreak of "mad rabbit disease" is unlikely.

PMID- 22416128
TI  - DNA methylation dynamics, metabolic fluxes, gene splicing, and alternative
      phenotypes in honey bees.
AB  - In honey bees (Apis mellifera), the development of a larva into either a queen or
      worker depends on differential feeding with royal jelly and involves epigenomic
      modifications by DNA methyltransferases. To understand the role of DNA
      methylation in this process we sequenced the larval methylomes in both queens and
      workers. We show that the number of differentially methylated genes (DMGs) in
      larval head is significantly increased relative to adult brain (2,399 vs. 560)
      with more than 80% of DMGs up-methylated in worker larvae. Several highly
      conserved metabolic and signaling pathways are enriched in methylated genes,
      underscoring the connection between dietary intake and metabolic flux. This
      includes genes related to juvenile hormone and insulin, two hormones shown
      previously to regulate caste determination. We also tie methylation data to
      expressional profiling and describe a distinct role for one of the DMGs encoding
      anaplastic lymphoma kinase (ALK), an important regulator of metabolism. We show
      that alk is not only differentially methylated and alternatively spliced in Apis,
      but also seems to be regulated by a cis-acting, anti-sense non-protein-coding
      transcript. The unusually complex regulation of ALK in Apis suggests that this
      protein could represent a previously unknown node in a process that activates
      downstream signaling according to a nutritional context. The correlation between
      methylation and alternative splicing of alk is consistent with the recently
      described mechanism involving RNA polymerase II pausing. Our study offers
      insights into diet-controlled development in Apis.

PMID- 22416130
TI  - Metabolic and regulatory rearrangements underlying efficient D-xylose utilization
      in engineered Pseudomonas putida S12.
AB  - Previously, an efficient D-xylose utilizing Pseudomonas putida S12 strain was
      obtained by introducing the D-xylose isomerase pathway from Escherichia coli,
      followed by evolutionary selection. In the present study, systemic changes
      associated with the evolved phenotype were identified by transcriptomics, enzyme
      activity analysis, and inverse engineering. A key element in improving the
      initially poor D-xylose utilization was the redistribution of 6-phospho-D
      gluconate (6-PG) between the Entner-Doudoroff pathway and the oxidative pentose
      phosphate (PP) pathway. This redistribution increased the availability of 6-PG
      for oxidative decarboxylation to D-ribose-5-phosphate, which is essential for the
      utilization of D-xylose via the nonoxidative PP pathway. The metabolic
      redistribution of 6-PG was procured by modified HexR regulation, which in
      addition appeared to control periplasmic sugar oxidation. Because the absence of
      periplasmic D-xylonate formation was previously demonstrated to be essential for
      achieving a high biomass yield on D-xylose, the aberrant HexR control appeared to
      underlie both the improved growth rate and biomass yield of the evolved D-xylose
      utilizing P. putida strain. The increased oxidative PP pathway activity
      furthermore resulted in an elevated NADH/NAD(+) ratio that caused the metabolic
      flux to be redirected from the TCA cycle to the glyoxylate shunt, which was also
      activated transcriptionally. Clearly, these findings may serve as an important
      case in point to engineer and improve the utilization of non-natural carbon
      sources in a wide range of industrial microorganisms.

PMID- 22416129
TI  - A novel heparin-dependent inhibitor of activated protein C that potentiates
      consumptive coagulopathy in Russell's viper envenomation.
AB  - The activation of coagulation factors V and X by Russell's viper venom (RVV) has
      been implicated in the development of consumptive coagulopathies in severely
      envenomed patients. However, factor Va is prone to inactivation by activated
      protein C (APC), an important serine protease that negatively regulates blood
      coagulation. It is therefore hypothesized that APC may be down-regulated by some
      of the venom components. In this study, we managed to isolate a potent Kunitz
      type APC inhibitor, named DrKIn-I. Using chromogenic substrate, DrKIn-I dose
      dependently inhibited the activity of APC. Heparin potentiated the inhibition and
      reduced the IC(50) of DrKIn-I by 25-fold. DrKIn-I, together with heparin, also
      protected factor Va from APC-mediated inactivation. Using surface plasmon
      resonance, DrKIn-I exhibited fast binding kinetics with APC (association rate
      constant = 1.7 * 10(7) M(-1) s(-1)). Direct binding assays and kinetic studies
      revealed that this inhibition (K(i) = 53 pM) is due to the tight binding
      interactions of DrKIn-I with both heparin and APC. DrKIn-I also effectively
      reversed the anticoagulant activity of APC and completely restored the thrombin
      generation in APC-containing plasma. Furthermore, although the injection of
      either DrKIn-I or RVV-X (the venom factor X-activator) into ICR mice did not
      significantly deplete the plasma fibrinogen concentration, co-administration of
      DrKIn-I with RVV-X resulted in complete fibrinogen consumption and the deposition
      of fibrin thrombi in the glomerular capillaries. Our results provide new insights
      into the pathogenesis of RVV-induced coagulopathies and indicate that DrKIn-I is
      a novel APC inhibitor that is associated with potentially fatal thrombotic
      complications in Russell's viper envenomation.

PMID- 22416131
TI  - System-wide studies of N-lysine acetylation in Rhodopseudomonas palustris reveal
      substrate specificity of protein acetyltransferases.
AB  - N-lysine acetylation is a posttranslational modification that has been well
      studied in eukaryotes and is likely widespread in prokaryotes as well. The
      central metabolic enzyme acetyl-CoA synthetase is regulated in both bacteria and
      eukaryotes by acetylation of a conserved lysine residue in the active site. In
      the purple photosynthetic alpha-proteobacterium Rhodopseudomonas palustris, two
      protein acetyltransferases (RpPat and the newly identified RpKatA) and two
      deacetylases (RpLdaA and RpSrtN) regulate the activities of AMP-forming acyl-CoA
      synthetases. In this work, we used LC/MS/MS to identify other proteins regulated
      by the N-lysine acetylation/deacetylation system of this bacterium. Of the 24
      putative acetylated proteins identified, 14 were identified more often in a
      strain lacking both deacetylases. Nine of these proteins were members of the AMP
      forming acyl-CoA synthetase family. RpPat acetylated all nine of the acyl-CoA
      synthetases identified by this work, and RpLdaA deacetylated eight of them. In
      all cases, acetylation occurred at the conserved lysine residue in the active
      site, and acetylation decreased activity of the enzymes by >70%. Our results show
      that many different AMP-forming acyl-CoA synthetases are regulated by N-lysine
      acetylation. Five non-acyl-CoA synthetases were identified as possibly
      acetylated, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and
      Rpa1177, a putative 4-oxalocrotonate tautomerase. Neither RpPat nor RpKatA
      acetylated either of these proteins in vitro. It has been reported that
      Salmonella enterica Pat (SePat) can acetylate a number of metabolic enzymes,
      including GAPDH, but we were unable to confirm this claim, suggesting that the
      substrate range of SePat is not as broad as suggested previously.

PMID- 22416132
TI  - Understanding the roles of nuclear A- and B-type lamins in brain development.
AB  - The nuclear lamina is composed mainly of lamins A and C (A-type lamins) and
      lamins B1 and B2 (B-type lamins). Dogma has held that lamins B1 and B2 play
      unique and essential roles in the nucleus of every eukaryotic cell. Recent
      studies have raised doubts about that view but have uncovered crucial roles for
      lamins B1 and B2 in neuronal migration during the development of the brain. The
      relevance of lamins A and C in the brain remains unclear, but it is intriguing
      that prelamin A expression in the brain is low and is regulated by miR-9, a brain
      specific microRNA.

PMID- 22416133
TI  - Vinculin functions as regulator of chondrogenesis.
AB  - To identify the genes involved in chondrocytic differentiation, we applied gene
      trap mutagenesis to a murine mesenchymal chondrogenic cell line ATDC5 and
      isolated a clone in which the gene encoding vinculin was trapped. The trapped
      allele was assumed to express a fusion protein containing a truncated vinculin
      lacking the tail domain and the geo product derived from the trap vector. The
      truncated vinculin was suggested to exert a dominant negative effect. Impaired
      functioning of vinculin caused by gene trapping in ATDC5 cells or knockdown in
      primary chondrocytes resulted in the reduced expression of chondrocyte-specific
      genes, including Col2a1, aggrecan, and Col10a1. The expression of Runx2 also was
      suppressed by the dysfunctional vinculin. On the other hand, the expression of
      Sox9, encoding a key transcription factor for chondrogenesis, was retained.
      Knockdown of vinculin in metatarsal organ cultures impaired the growth of the
      explants and reduced the expression of Col2a1 and aggrecan. Gene trapping or
      knockdown of vinculin decreased the phosphorylation of ERK1/2 but increased that
      of Src homology 2 domain-containing tyrosine phosphatase 2 (SHP2) and Akt during
      chondrocytic differentiation, suggesting a disturbance of signaling by insulin
      like growth factor I (IGF-I). Knockdown of vinculin in the metatarsal organ
      culture abrogated the IGF-I-induced growth and inhibited the up-regulation of
      Col2a1 and aggrecan expression by IGF-I. Loss of vinculin function in
      differentiating chondrocytes impaired the activation of the p38 MAPK pathway
      also, suggesting its involvement in the regulation of chondrogenesis by vinculin.
      Our results indicate a tissue-specific function of vinculin in cartilage whereby
      it controls chondrocytic differentiation.

PMID- 22416134
TI  - Leucine zipper domain is required for Kaposi sarcoma-associated herpesvirus
      (KSHV) K-bZIP protein to interact with histone deacetylase and is important for
      KSHV replication.
AB  - The Kaposi sarcoma-associated herpesvirus (KSHV; or human herpesvirus-8)-encoded
      protein called K-bZIP (also named K8) was found to be multifunctional. In this
      study, we discovered that K-bZIP interacts with histone deacetylase (HDAC) 1/2 in
      12-O-tetradecanoylphorbol-13-acetate-stimulated BCBL-1 lymphocyte cells. K-bZIP
      appears to repress HDAC activity through this interaction, which we determined to
      be independent of K-bZIP SUMOylation. We dissected the domains of K-bZIP and
      found that the leucine zipper (LZ) domain is essential for the interaction of K
      bZIP and HDAC. In addition, we constructed a KSHV bacterial artificial chromosome
      (BAC) with LZ domain-deleted K-bZIP (KSHVdLZ) and transfected this mutated KSHV
      BAC DNA into HEK 293T cells. As a result, it was consistently found that K-bZIP
      without its LZ domain failed to interact with HDAC2. We also showed that the
      interaction between K-bZIP and HDAC is necessary for the inhibition of the lytic
      gene promoters (ORF50 and OriLyt) of KSHV by K-bZIP. Furthermore, we found that
      the LZ domain is also important for the interaction of K-bZIP with the promoters
      of ORF50 and OriLyt. Most interestingly, although it was found to have
      suppressive effects on the promoters of ORF50 and OriLyt, KSHVdLZ replicates at a
      significantly lower level than its BAC-derived revertant (KSHVdLZRev) or KSHVWT
      (BAC36) in HEK 293T cells. The defectiveness of KSHVdLZ replication can be
      partially rescued by siRNA against HDAC2. Our results suggest that the function
      of K-bZIP interaction with HDAC is two-layered. 1) K-bZIP inhibits HDAC activity
      generally so that KSHVdLZ replicates at a lower level than does KSHVWT. 2) K-bZIP
      can recruit HDAC to the promoters of OriLyt and ORF50 through interaction with
      HDAC for K-bZIP to have a temporary repressive effect on the two promoters.

PMID- 22416135
TI  - Molecular basis of the interaction between proapoptotic truncated BID (tBID)
      protein and mitochondrial carrier homologue 2 (MTCH2) protein: key players in
      mitochondrial death pathway.
AB  - The molecular basis of the interaction between mitochondrial carrier homologue 2
      (MTCH2) and truncated BID (tBID) was characterized. These proteins participate in
      the apoptotic pathway, and the interaction between them may serve as a target for
      anticancer lead compounds. In response to apoptotic signals, MTCH2 recruits tBID
      to the mitochondria, where it activates apoptosis. A combination of peptide
      arrays screening with biochemical and biophysical techniques was used to
      characterize the mechanism of the interaction between tBID and MTCH2 at the
      structural and molecular levels. The regions that mediate the interaction between
      the proteins were identified. The two specific binding sites between the proteins
      were determined to be tBID residues 59-73 that bind MTCH2 residues 140-161, and
      tBID residues 111-125 that bind MTCH2 residues 240-290. Peptides derived from
      tBID residues 111-125 and 59-73 induced cell death in osteosarcoma cells. These
      peptides may serve as lead compounds for anticancer drugs that act by targeting
      the tBID-MTCH2 interaction.

PMID- 22416136
TI  - Tight complex formation between Cosmc chaperone and its specific client non
      native T-synthase leads to enzyme activity and client-driven dissociation.
AB  - The interaction of the endoplasmic reticulum molecular chaperone Cosmc with its
      specific client T-synthase (Core 1 beta1-3-galactosyltransferase) is required for
      folding of the enzyme and eventual movement of the T-synthase to the Golgi, but
      the mechanism of interaction is unclear. Here we show that the lumenal domain of
      recombinant Cosmc directly interacts specifically in either free form or
      covalently bound to solid supports with denatured T-synthase but not with the
      active dimeric form of the enzyme. This leads to formation of a relatively stable
      complex of Cosmc and denatured T-synthase accompanied by formation of reactivated
      enzyme in an ATP-independent fashion that is not regulated by redox, calcium, pH,
      or intermolecular disulfide bond formation. The partly refolded and active T
      synthase remains tightly bound noncovalently to Cosmc. Dissociation of T-synthase
      from the complex is promoted by further interactions of the complex with free
      forms of either native or non-native T-synthase. Taken together, these results
      demonstrate a novel mechanism in which Cosmc cycles to bind non-native T
      synthase, leading to enzyme activity and release in a client-driven process.

PMID- 22416137
TI  - Neurotensin-induced proinflammatory signaling in human colonocytes is regulated
      by beta-arrestins and endothelin-converting enzyme-1-dependent endocytosis and
      resensitization of neurotensin receptor 1.
AB  - The neuropeptide/hormone neurotensin (NT) mediates intestinal inflammation and
      cell proliferation by binding of its high affinity receptor, neurotensin receptor
      1 (NTR1). NT stimulates IL-8 expression in NCM460 human colonic epithelial cells
      by both MAP kinase- and NF-kappaB-dependent pathways. Although the mechanism of
      NTR1 endocytosis has been studied, the relationship between NTR1 intracellular
      trafficking and inflammatory signaling remains to be elucidated. In the present
      study, we show that in NCM460 cells exposed to NT, beta-arrestin-1 (betaARR1),
      and beta-arrestin-2 (betaARR2) translocate to early endosomes together with NTR1.
      Endothelin-converting enzyme-1 (ECE-1) degrades NT in acidic conditions, and its
      activity is crucial for NTR1 recycling. Pretreatment of NCM460 cells with the ECE
      1 inhibitor SM19712 or gene silencing of betaARR1 or betaARR2 inhibits NT
      stimulated ERK1/2 and JNK phosphorylation, NF-kappaB p65 nuclear translocation
      and phosphorylation, and IL-8 secretion. Furthermore, NT-induced cell
      proliferation, but not IL-8 transcription, is attenuated by the JNK inhibitor,
      JNK(AII). Thus, NTR1 internalization and recycling in human colonic epithelial
      cells involves betaARRs and ECE-1, respectively. Our results also indicate that
      betaARRs and ECE-1-dependent recycling regulate MAP kinase and NF-kappaB
      signaling as well as cell proliferation in human colonocytes in response to NT.

PMID- 22416138
TI  - Molecular basis of requirement of receptor activator of nuclear factor kappaB
      signaling for interleukin 1-mediated osteoclastogenesis.
AB  - IL-1, a proinflammatory cytokine, is implicated in bone loss in various
      pathological conditions by promoting osteoclast formation, survival, and
      function. Although IL-1 alone can sufficiently prolong osteoclast survival and
      activate osteoclast function, IL-1-mediated osteoclastogenesis requires the
      receptor activator of NF-kappaB (RANK) ligand (RANKL). However, the molecular
      basis of the dependence of IL-1-mediated osteoclastogenesis on RANKL is not fully
      understood. Here we show that although IL-1 cannot activate the expression of the
      osteoclast genes encoding matrix metalloproteinase 9, cathepsin K, tartrate
      resistant acid phosphatase, and carbonic anhydrase II in bone marrow macrophages
      (BMMs), RANKL renders these osteoclast genes responsive to IL-1. We further
      demonstrate that IL-1 alone fails to induce the expression of nuclear factor of
      activated T cell cytoplasmic 1 (NFATc1), a master transcriptional regulator of
      osteoclastogenesis), in BMMs but can up-regulate its expression in the presence
      of permissive levels of RANKL or with RANKL pretreatment. The RANK IVVY motif,
      which has been previously shown to commit BMMs to the osteoclast lineage in RANKL
      and TNF alpha-mediated osteoclastogenesis, also plays a crucial role in IL-1
      mediated osteoclastogenesis by changing the four osteoclast marker and NFATc1
      genes to an IL-1-inducible state. Finally, we show that MyD88, a known critical
      component of the IL-1 receptor I signaling pathway, plays a crucial role in IL-1
      mediated osteoclastogenesis from RANKL-primed BMMs by up-regulating the
      expression of the osteoclast marker and NFATc1 genes. This study reveals a novel
      mechanism of IL-1-mediated osteoclastogenesis and supports the promising
      potential of the IVVY motif to serve as a therapeutic target for inflammatory
      bone loss.

PMID- 22416139
TI  - Novel basic protein, PfN23, functions as key macromolecule during nacre
      formation.
AB  - The fine microstructure of nacre (mother of pearl) illustrates the beauty of
      nature. Proteins found in nacre were believed to be "natural hands" that control
      nacre formation. In the classical view of nacre formation, nucleation of the main
      minerals, calcium carbonate, is induced on and by the acidic proteins in nacre.
      However, the basic proteins were not expected to be components of nacre. Here, we
      reported that a novel basic protein, PfN23, was a key accelerator in the control
      over crystal growth in nacre. The expression profile, in situ immunostaining, and
      in vitro immunodetection assays showed that PfN23 was localized within calcium
      carbonate crystals in the nacre. Knocking down the expression of PfN23 in adults
      via double-stranded RNA injection led to a disordered nacre surface in adults.
      Blocking the translation of PfN23 in embryos using morpholino oligomers led to
      the arrest of larval development. The in vitro crystallization assay showed that
      PfN23 increases the rate of calcium carbonate deposition and induced the
      formation of aragonite crystals with characteristics close to nacre. In addition,
      we constructed the peptides and truncations of different regions of this protein
      and found that the positively charged C-terminal region was a key region for the
      function of PfN23 Taken together, the basic protein PfN23 may be a key
      accelerator in the control of crystal growth in nacre. This provides a valuable
      balance to the classic view that acidic proteins control calcium carbonate
      deposition in nacre.

PMID- 22416140
TI  - SIRT3 protein deacetylates isocitrate dehydrogenase 2 (IDH2) and regulates
      mitochondrial redox status.
AB  - Mitochondria play a central role in oxidative energy metabolism and age-related
      diseases such as cancer. Accumulation of spurious oxidative damage can cause
      cellular dysfunction. Antioxidant pathways that rely on NADPH are needed for the
      reduction of glutathione and maintenance of proper redox status. The
      mitochondrial matrix protein isocitrate dehydrogenase 2 (IDH2) is a major source
      of NADPH. Previously, we demonstrated that the NAD(+)-dependent deacetylase SIRT3
      was essential for the prevention of age-related hearing loss in mice fed a
      calorically restricted diet. Here we provide direct biochemical and biological
      evidence establishing an exquisite regulatory relationship between IDH2 and SIRT3
      under acute and chronic caloric restriction. The regulated site of acetylation
      was mapped to Lys-413, an evolutionarily invariant residue. Site-specific,
      genetic incorporation of N(epsilon)-acetyllysine into position 413 of IDH2
      revealed that acetylated IDH2 displays a dramatic 44-fold loss in activity.
      Deacetylation by SIRT3 fully restored maximum IDH2 activity. The ability of SIRT3
      to protect cells from oxidative stress was dependent on IDH2, and the
      deacetylated mimic, IDH2(K413R) variant was able to protect Sirt3(-/-) mouse
      embryonic fibroblasts from oxidative stress through increased reduced glutathione
      levels. Together these results uncover a previously unknown mechanism by which
      SIRT3 regulates IDH2 under dietary restriction. Recent findings demonstrate that
      IDH2 activities are a major factor in cancer, and as such, these results
      implicate SIRT3 as a potential regulator of IDH2-dependent functions in cancer
      cell metabolism.

PMID- 22416141
TI  - Gene of the month: PTEN.

PMID- 22416142
TI  - An Arabidopsis rhomboid protease has roles in the chloroplast and in flower
      development.
AB  - Increasing numbers of cellular pathways are now recognized to be regulated via
      proteolytic processing events. The rhomboid family of serine proteases plays a
      pivotal role in a diverse range of pathways, activating and releasing proteins
      via regulated intramembrane proteolysis. The prototype rhomboid protease,
      rhomboid-1 in Drosophila, is the key activator of epidermal growth factor (EGF)
      receptor pathway signalling in the fly and thus affects multiple aspects of
      development. The role of the rhomboid family in plants is explored and another
      developmental phenotype, this time in a mutant of an Arabidopsis chloroplast
      localized rhomboid, is reported here. It is confirmed by GFP-protein fusion that
      this protease is located in the envelope of chloroplasts and of chlorophyll-free
      plastids elsewhere in the plant. Mutant plants lacking this organellar rhomboid
      demonstrate reduced fertility, as documented previously with KOM-the one other
      Arabidopsis rhomboid mutant that has been reported in the literature-along with
      aberrant floral morphology.

PMID- 22416143
TI  - Environmental Change, Risky Sexual Behavior, and the HIV/AIDS Pandemic: Linkages
      Through Livelihoods in Rural Haiti.
AB  - Local natural resources are central to rural livelihoods across much of the
      developing world. Such "natural capital" represents one of several types of
      assets available to households as they craft livelihood strategies. In order to
      explore the potential for environmental scarcity and change to contribute to
      perpetuation of the HIV/AIDS pandemic, we examine the association between
      declining natural capital and engaging in risky sexual behaviors, as potentially
      another livelihood strategy. Such association has been demonstrated in Kenya and
      Tanzania, through the fish-for-sex trade. To explore the possibility of this
      connection within rural Haitian livelihoods we use Demographic and Health Survey
      data, with a focus on rural women, combined with vegetation measures generated
      from satellite imagery. We find that lack of condom use in recent sexual
      encounters is associated with local environmental scarcity - controlling for
      respondent age, education, religion and knowledge of AIDS preventive measures.
      The results suggest that explicit consideration of the environmental dimensions
      of HIV/AIDS may be of relevance in scholarship examining factors shaping the
      pandemic.

PMID- 22416145
TI  - What's new in Emergencies, Trauma and Shock? Resuscitation guidelines update in
      2010: Implications for bystander CPR.

PMID- 22416146
TI  - Complications of bystander cardiopulmonary resuscitation for unconscious patients
      without cardiopulmonary arrest.
AB  - BACKGROUND: Insufficient knowledge of the risks and complications of
      cardiopulmonary resuscitation (CPR) may be an obstructive factor for CPR,
      however, particularly for patients who are not clearly suffering out of hospital
      cardiopulmonary arrest (OH-CPA). The object of this study was to clarify the
      potential complication, the safety of bystander CPR in such cases. MATERIALS AND
      METHODS: This study was a population-based observational case series. To be
      enrolled, patients had to have undergone CPR with chest compressions performed by
      lay persons, had to be confirmed not to have suffered OHCPA. Complications of
      bystander CPR were identified from the patients' medical records and included rib
      fracture, lung injury, abdominal organ injury, and chest and/or abdominal pain
      requiring analgesics. In our emergency department, one doctor gathered
      information while others performed X-ray and blood examinations,
      electrocardiograms, and chest and abdominal ultrasonography. RESULTS: A total of
      26 cases were the subjects. The mean duration of bystander CPR was 6.5 minutes
      (ranging from 1 to 26). Nine patients died of a causative pathological condition
      and pneumonia, and the remaining 17 survived to discharge. Three patients
      suffered from complications (tracheal bleeding, minor gastric mucosal laceration,
      and chest pain), all of which were minimal and easily treated. No case required
      special examination or treatment for the complication itself. CONCLUSION: The
      risk and frequency of complications due to bystander CPR is thought to be very
      low. It is reasonable to perform immediate CPR for unconscious victims with
      inadequate respiration, and to help bystanders perform CPR using the T-CPR
      system.

PMID- 22416147
TI  - Transforming trauma healthcare delivery in rural areas by use of an integrated
      call center.
AB  - INTRODUCTION: There is poor penetration of trauma healthcare delivery in rural
      areas. On the other hand, mobile penetration in India is now averaging 80% with
      most families having access to mobile phone. AIMS AND OBJECTIVES: The aim of this
      study was to assess the implementation and socioeconomic impact of a call center
      in providing healthcare delivery for patients with head and spinal injuries.
      MATERIALS AND METHODS: This was a prospective observational study carried out
      over a 6-month period at a level I trauma Center in New Delhi, India. A nine
      seater call center was outsourced to a private company and the hospital's
      electronic medical records were integrated with the call-center operations. The
      call center was given responsibility of maintaining appointments and scheduling
      clinics for the whole hospital as well as ensuring follow-up visits. Trained call
      center staff handled simple patient queries and referred the rest via email to
      concerned doctors. A telephonic survey was done prior to the start of call-center
      operations and after 3 months to assess for user satisfaction. RESULTS: The
      initial cost of outsourcing the call center was Rs 1.6 lakhs (US$ 4000), with a
      recurring cost of Rs 80,000 (US$ 2000) per month. A total of 484 patients were
      admitted in the department of Neurosurgery during the study period. Of these, 63%
      (n=305) were from rural areas. Patients' overall experience for clinic visits
      improved markedly following implementation of call center. Patient satisfaction
      for follow-up visits increased from a mean of 32-96%. Ninety-five percent
      patients reported a significant decrease in waiting time in clinics 80.4%
      reporting improved doctor-patient interaction. A total of 52 visits could be
      postponed/cancelled for patients living in far flung areas resulting in major
      socioeconomic benefits to these families. CONCLUSIONS: As shown by our case
      study, call centers have the potential to revolutionize delivery of trauma
      healthcare to rural areas in an extremely cost-effective manner.

PMID- 22416148
TI  - Venous thromboembolic events in isolated severe traumatic brain injury.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of
      prophylactic anticoagulation on the incidence of venous thromboembolic events
      (VTE) in patients suffering from isolated severe traumatic brain injury (TBI).
      MATERIALS AND METHODS: Retrospective matched case-control study in adult patients
      sustaining isolated severe TBI (head AIS >=3, with extracranial AIS <=2)
      receiving VTE prophylaxis while in the surgical intensive care unit from 1/2007
      through 12/2009. Patients subjected to VTE prophylaxis were matched 1:1 by age,
      gender, glasgow coma scale (GCS) score at admission, presence of hypotension on
      admission, injury severity score, and head abbreviated injury scale (AIS) score,
      with patients who did not receive chemical VTE prophylaxis. The primary outcome
      measure was VTE. Secondary outcomes were SICU and hospital length of stay (HLOS),
      adverse effects of anticoagulation, and mortality. RESULTS: After propensity
      matching, 37 matched pairs were analysed. Cases and controls had similar
      demographics, injury characteristics, rate of craniotomies/craniectomies, SICU
      LOS, and HLOS. The median time of commencement of VTE prophylaxis was 10 days.
      The incidence of VTE was increased 3.5-fold in the controls compared to the cases
      (95% CI 1.0-12.1, P=0.002). The mortality was higher in patients who did not
      receive anticoagulation (19% vs. 5%, P=0.001). No adverse outcomes were detected
      in the anticoagulated patients. CONCLUSION: Prophylactic anticoagulation
      decreases the overall risk for clinically significant VTE in patients with severe
      isolated TBI. Prospective validation of the timing and safety of chemical VTE
      prophylaxis in these instances is warranted.

PMID- 22416149
TI  - Different causes of referral to ophthalmology emergency room.
AB  - BACKGROUND: Eye-related complaints compose approximately 1-6% of complaints of
      patients referring to general emergency ward around the world. Eye injuries are
      the most common cause of referral to eye emergency ward. To understand the impact
      of eye injuries in Iran and to plan preventive strategies, it is important to
      understand the complete magnitude of the problem with regard to true population
      based data and standard reproducible definitions. AIM: The main goal of this
      study was to identify the major causes of referrals to eye emergency ward in
      patients with eye-related complaints in an eye referral Hospital in Iran.
      SETTINGS AND DESIGN: In a cross-sectional study, 3150 patients who referred to
      Farabi Hospital emergency ward, Tehran, Iran, from January to December 2007 were
      included in the study and their detailed information were recorded. MATERIALS AND
      METHODS: The patients' demographic data, medical history and final diagnosis were
      recorded in a questionnaire. RESULTS: The mean age of patients was 33.2+/-16.8
      years and 2380 patients (75.6%) were males. While 299 patients (9.5%) were
      referred for non-urgent reasons, work-related injuries were the most common cause
      of referral (955 patients; 30.3%). In patients referred due to trauma (1950
      patients), work-related injuries occurred in 955 patients (49%) and occurred
      accidentally (by chance) in 819 patients (42%). The majority of patients referred
      with traumatic injuries were males (1708 patients; 87.6% versus 242 patients;
      12.4%). The most common etiologies of eye trauma (1950 patients) were metal
      filings (814 patients; 41.8%), blunt trauma (338 patients; 17.3%), fireworks (236
      patients; 12.1%) and sharp objects (222 patients; 11.4%). Globe injury was
      diagnosed in 1865 patients (95.7%) of trauma cases. In patients referred due to
      non-traumatic reason (1200 patients), eye infection occurred in 482 patients
      (40.2%) and 299 patients (24.9%) were referred for non-urgent reasons. There was
      little difference between the frequency of non-trauma-related problems among
      genders (672 male patients; 56% versus 528 female patients; 44%). CONCLUSIONS:
      This study identified multiple risk factors whose presence significantly
      increases severity of an eye injury. Male gender, youth and unprotected eyes
      during high-risk activities such as sports and certain jobs are risk factors for
      eye injuries. In patients referred due to non-traumatic reasons, males and
      females are similar. Considerable proportion of non-trauma-related problems was
      due to eye infection, that one of the most important reasons may be connected to
      the increasing use of contact lenses in our target population. Thereupon, we need
      for further educative and preventive interventions at the level of general
      population.

PMID- 22416150
TI  - Teamwork in the trauma room evaluation of a multimodal team training program.
AB  - INTRODUCTION: Poor teamwork leads to preventable medical errors, and thus
      negatively impacts medical care. One way to improve teamwork is training. A
      multimodality team training program was designed to impact the attitudes and
      behavior of first-year residents who will encounter medical situations in the
      trauma room. The training program included low-fidelity role plays, lectures, and
      high-fidelity simulation with feedback. MATERIALS AND METHODS: The training
      program was a one-day workshop that was conducted twice, once for each of the two
      groups over two days at the beginning of the academic year in July. A total of 41
      first-year interns (10 Emergency Medicine and 31 Surgery) were recruited for
      participation. Participants completed a Situational judgment test (SJT) on trauma
      teamwork before training. The training began with a low-fidelity simulation that
      served as an icebreaker to team concepts. Subsequently, a lecture with discussion
      provided key points regarding teamwork in the trauma room. A high-fidelity
      simulation then allowed participation in one of four trauma room scenarios with
      medical expert debriefing. The course concluded with a course summary and an
      assessment of participant attitudes regarding training along with a second
      administration of SJT. RESULTS: Participant reactions to the training were
      positive overall. Results of SJT showed a positive effect for team training in
      three of the four possible comparisons. CONCLUSION: The program was well received
      by the residents. Results suggest that a comprehensive training approach using
      role play, lecture, and simulation can positively affect behavioral choices for
      teamwork in the trauma room.

PMID- 22416151
TI  - Feasibility and safety of ultrasound-guided nerve block for management of limb
      injuries by emergency care physicians.
AB  - BACKGROUND: Patients require procedural sedation and analgesia (PSA) for the
      treatment of acute traumatic injuries. PSA has complications. Ultrasound (US)
      guided peripheral nerve block is a safe alternative. AIM: Ultrasound guided nerve
      blocks for management of traumatic limb emergencies in Emergency Department (ED).
      SETTING AND DESIGN: Prospective observational study conducted in ED. MATERIALS
      AND METHODS: Patients above five years requiring analgesia for management of limb
      emergencies were recruited. Emergency Physicians trained in US guided nerve
      blocks performed the procedure. STATISTICAL ANALYSIS: Effectiveness of pain
      control, using visual analogue scale was assessed at baseline and at 15 and 60
      minutes after the procedure. Paired t test was used for comparison. RESULTS:
      Fifty US guided nerve blocks were sciatic- 4 (8%), femoral-7 (14%), brachial- 29
      (58%), median -6 (12%), and radial 2 (4%) nerves. No patients required rescue
      PSA. Initial median VAS score was 9 (Inter Quartile Range [IQR] 7-10) and at 1
      hour was 2(IQR 0-4). Median reduction in VAS score was 7.44 (IQR 8-10(75%), 1
      2(25%) (P=0.0001). Median procedure time was 9 minutes (IQR 3, 12 minutes) and
      median time to reduction of pain was 5 minutes (IQR 1,15 minutes). No immediate
      or late complications noticed at 3 months. CONCLUSION: Ultrasound-guided nerve
      blocks can be safely and effectively performed for upper and lower limb
      emergencies by emergency physicians with adequate training.

PMID- 22416152
TI  - Evaluating conservative treatment for acute appendicitis with lump formation.
AB  - BACKGROUND: Interval appendectomy after acute appendicitis with lump formation
      (phlegmon) remains controversial. We conducted this study to determine the risk
      of recurrent appendicitis following initial non-operative treatment for
      appendicitis, and evaluate factors associated with recurrence. Secondarily, we
      evaluate the efficacy of interval appendectomy versus no appendectomy. MATERIALS
      AND METHODS: Patients who received conservative treatment for appendicitis with
      lump formation were prospectively studied from June 2006 to June 2008. These
      patients were followed for recurrence of appendicitis. RESULTS: Of 763 patients
      with acute appendicitis some 220 patients had lump formation (28.8%). Median age
      was 28 years. Conservative treatment was successful in 213 (96.8%) patients. The
      rate of recurrence was 13.1%, all occurring within six months after the index
      admission. Mean follow-up was 26+/-18 months. CONCLUSION: Conservative treatment
      of appendicitis with lump formation is efficient and the recurrence rate is low.
      Routine interval appendectomy after initial conservative treatment for lump
      formation is not a cost-effective intervention and not recommended.

PMID- 22416153
TI  - The results of the three-month co-operation between a German and a Greek surgical
      team in a role II military hospital in Afghanistan.
AB  - BACKGROUND AND AIM: There are a lot of unique challenges for the military medical
      personnel assigned to Afghanistan. We evaluate the results of the co-operation
      between a German and a Greek surgical team during a 3-month period in a role II
      hospital. MATERIALS AND METHODS: Patients who were admitted to the role II German
      hospital of Kunduz were evaluated. We reviewed the type of diseases, mechanism
      and location of injuries, management, types of surgical procedures, blood supply,
      and outcome. RESULTS: The data included 792 ISAF patients, 18 NGOs patients, and
      296 local patients. Out of them, 71.6% of the patients were ISAF personnel; 51
      patients underwent a surgical operation; 35 of them were operated in an emergency
      base. Fifty-five surgical procedures were performed. In 22 (43.1%) of these
      patients, orthopedic procedures were performed, while in the rest 29 (56.9%)
      patients the operations were of general surgery interest. Gunshot injuries were
      the main mechanism of injury for locals, whereas ISAF personnel were usually
      presented with injuries after IEDs and rocket attacks. A total number of 11
      patients were transferred to role III military hospitals for further treatment
      within 24 hours. CONCLUSIONS: The co-operation between surgical teams from
      different countries, when appropriately trained, staffed, and equipped, can be
      highly effective in a combat environment.

PMID- 22416154
TI  - Injury-related mortality audit in a regional trauma center at Puducherry, India.
AB  - BACKGROUND: There is an alarming trend of injuries leading to poor outcome of
      victims in India. OBJECTIVE: To study the profile of patients who died due to
      trauma and to identify factors involved in both pre-hospital and hospital care.
      MATERIALS AND METHODS: A hospital-based study was performed at a trauma center in
      Puducherry from June 2009 to May 2010. Patients who had at least one sign of life
      on admission and later died were included. The demographic characteristics,
      injury mechanism, nature and site of injury, influence of alcohol, pre-hospital
      time and care, distance traveled, number of referrals, time spent in study
      hospital, cause of death, and missed injuries revealed at post mortem were noted.
      RESULTS: Of the 204 fatal cases, most were between 25-65 years of age (77%);
      sustained injuries over weekends (36%) and between 4 pm and midnight (41%); had
      at least one halt in a medical facility before reaching definitive care (56%);
      and died within a week (63%). Adults (25-65 y) sustained most injuries (77%) on
      two wheelers. In those aged over 65 years, 79 percent were pedestrians. Road
      traffic injuries were responsible for 82 % of deaths; 16 percent were reportedly
      under the influence of alcohol at the time of injury. Mean delay from the time of
      accident to admission was 14.9 hours and median distance traveled was 30
      kilometers. Head injury was the most common (66%) cause of death. Post mortem
      revealed skull fractures (37%), while missed injuries were noted in 8 percent,
      mostly involving the cervical spine and chest wall. CONCLUSION: The problem of
      trauma care needs to be addressed urgently in this part of southern India to
      reduce mortality and morbidity.

PMID- 22416155
TI  - Who killed Rambhor?: The state of emergency medical services in India.
AB  - In India, the healthcare delivery system starts up from the sub-center at the
      village level and reaches up to super specialty medical centers providing state
      of the art emergency medical services (EMS). These highest centers, located in
      big cities, are considered the last referral points for the patients from nearby
      cities and states. As the incidents of rail and road accidents have increased in
      recent years, the role of EMS becomes critical in saving precious lives. But when
      the facilities and management of these emergency centers succumbs before the
      patient, then the question arises regarding the adequate availability and quality
      of EMS. The death of an unknown common man, Rambhor, for want of EMS in three big
      hospitals in the national capital of India put a big question on the "health" of
      the emergency health services in India. The emergency services infrastructure
      seems inadequate and quality and timely provision of EMS to critical patients
      appears unsatisfactory. There is lack of emergency medicine (EM) specialists in
      India and also the postgraduation courses in EM have not gained foot in our
      medical education system. Creation of a Centralized Medical Emergency Body,
      implementation of management techniques, modification of medical curriculum, and
      fixing accountability are some of the few steps which are required to improve the
      EMS in India.

PMID- 22416157
TI  - The injured child in Africa.

PMID- 22416156
TI  - Pediatric trauma in sub-Saharan Africa: Challenges in overcoming the scourge.
AB  - All over the world, pediatric trauma has emerged as an important public health
      problem. It accounts for the highest mortality in children and young adults in
      developed countries. Reports from Africa on trauma in the pediatric age group are
      few and most have been single center experience. In many low-and middle-income
      countries, the death rates from trauma in the pediatric age group exceed those
      found in developed countries. Much of this mortality is preventable by developing
      suitable preventive measures, implementing an effective trauma system and
      adapting interventions that have been implemented in developed countries that
      have led to significant reduction in both morbidity and mortality. This review of
      literature on the subject by pediatric and orthopedic surgeons from different
      centers in Africa aims to highlight the challenges faced in the care of these
      patients and proffer solutions to the scourge.

PMID- 22416158
TI  - Strategies for coping with stress in emergency medicine: Early education is
      vital.
AB  - INTRODUCTION: Physician burnout has received considerable attention in the
      literature and impacts a large number of emergency medicine physicians, but there
      is no standardized curriculum for wellness in resident education. A culture
      change is needed to educate about wellness, adopt a preventative and proactive
      approach, and focus on resiliency. DISCUSSION: We describe a novel approach to
      wellness education by focusing on resiliency rather than the unintended endpoint
      of physician burnout. One barrier to adoption of wellness education has been
      establishing legitimacy among emergency medicine (EM) residents and educators. We
      discuss a change in the language of wellness education and provide several
      specific topics to facilitate the incorporation of these topics in resident
      education. CONCLUSION: Wellness education and a culture of training that promotes
      well-being will benefit EM residents. Demonstrating the impact of several factors
      that positively affect emergency physicians may help to facilitate alert
      residents to the importance of practicing activities that will result in
      wellness. A change in culture and focus on resiliency is needed to adequately
      address and optimize physician self-care.

PMID- 22416159
TI  - Point-of-care ultrasound in critically ill patients: Where do we stand?
AB  - Experience over the last 25 years has shown that point-of-care ultrasound is a
      very useful tool when used by nonradiologists. Its value will be optimized by
      understanding its limitations and by adopting a focused binary decision making
      approach to answer specific questions without going into detailed radiological
      studies. Point-of-care ultrasound became an extension of the clinical
      examination. There are extensive efforts trying to design low-cost portable
      ultrasound systems by changing the transducer design, the transmission and
      reception circuitry needs, or the beam forming algorithms which may lead to
      horizontal expansion of the use of reliable non expensive portable ultrasound
      machines. The successful story of using ultrasound by nonradiologists, the
      advanced technology, and the refinement of the educational methods will encourage
      future clinicians to use ultrasound in their domains.

PMID- 22416160
TI  - The role of bedside ultrasound in the diagnosis of pericardial effusion and
      cardiac tamponade.
AB  - This review article discusses two clinical cases of patients presenting to the
      emergency department with pericardial effusions. The role of bedside ultrasound
      in the detection of pericardial effusions is investigated, with special attention
      to the specific ultrasound features of cardiac tamponade. Through this review,
      clinicians caring for patients with pericardial effusions will learn to rapidly
      diagnose this condition directly at the bedside. Clinicians will also learn to
      differentiate between simple pericardial effusions in contrast to more
      complicated effusions causing cardiac tamponade. Indications for emergency
      pericardiocentesis are covered, so that clinicians can rapidly determine which
      group of patients will benefit from an emergency procedure to drain the effusion.

PMID- 22416161
TI  - Sonographic diagnosis of pneumothorax.
AB  - Lung sonography has rapidly emerged as a reliable technique in the evaluation of
      various thoracic diseases. One important, well-established application is the
      diagnosis of a pneumothorax. Prompt and accurate diagnosis of a pneumothorax in
      the management of a critical patient can prevent the progression into a life
      threatening situation. Sonographic signs, including 'lung sliding', 'B-lines' or
      'comet tail artifacts', 'A-lines', and 'the lung point sign' can help in the
      diagnosis of a pneumothorax. Ultrasound has a higher sensitivity than the
      traditional upright anteroposterior chest radiography (CXR) for the detection of
      a pneumothorax. Small occult pneumothoraces may be missed on CXR during a busy
      trauma scenario, and CXR may not always be feasible in critically ill patients.
      Computed tomography, the gold standard for the detection of pneumothorax,
      requires patients to be transported out of the clinical area, compromising their
      hemodynamic stability and delaying the diagnosis. As ultrasound machines have
      become more portable and easier to use, lung sonography now allows a rapid
      evaluation of an unstable patient, at the bedside. These advantages combined with
      the low cost and ease of use, have allowed thoracic sonography to become a useful
      modality in many clinical settings.

PMID- 22416162
TI  - Sonography of gangrenous cholecystitis.
AB  - Gangrenous cholecystitis is an acute surgical emergency, which requires early
      cholecystectomy. Differentiation of patients with gangrenous cholecystitis from
      those with non-gangrenous cholecystitis can be difficult, both clinically and
      with imaging. Careful attention to the following sonographic signs suggests the
      presence of gangrenous cholecystitis decreased focal wall perfusion on Color
      Doppler, irregular gall bladder mucosal outline, gall bladder wall thickening
      with signs of de-lamination, gas within the gall bladder, absence of calculi, and
      large peri-cholecystic collections. Both sonogram with color flow imaging and
      contrast-enhanced Computed tomography are complementary investigations to
      establish this important diagnosis in critically ill patients.

PMID- 22416163
TI  - The role of ultrasound in the management of intestinal obstruction.
AB  - Intestinal obstruction (IO) is a common cause of acute abdominal pain. The recent
      increased use of sonography in the initial evaluation of abdominal pain has made
      point-of-care ultrasound a valuable tool for the diagnosis of IO. Sonography is
      as sensitive, but more specific, than plain abdominal X-ray in the diagnosis of
      IO. Point-of-care ultrasound can answer specific questions related to IO that
      assist the acute care physician in critical decision making. Sonography can also
      help in the resuscitation of patients by serial measurement of the IVC diameter.
      We review the sonographic findings of IO and the role of point-of-care ultrasound
      in the management of patients having IO.

PMID- 22416164
TI  - Humoral hypercalcemic crisis in a pregnant woman with uterine leiomyoma.
AB  - We report a case of parathyroid hormone-related protein-mediated hypercalcemic
      crisis in a 36-year-old pregnant woman, who was admitted to women hospital with
      recurrent vomiting and epigastric pain. She was diagnosed with uterine fibroid
      since the first month of her pregnancy, but the pregnancy had been uneventful.
      Serum calcium was 4.8 mmol/l, while parathyroid hormone was low. Hypercalcemia
      was attributed to humoral hypercalcemia associated with uterine fibroid as other
      causes of hypercalcemia were excluded.

PMID- 22416165
TI  - Ketotic hyperglycemia with movement disorder.
AB  - Chorea, hemichorea-hemiballismus and severe partial seizures may be the
      presenting features of nonketotic hyperglycemia in older adults with type 2
      diabetes, but cases in young adults with type 1 diabetes are rare. We hereby
      report a very rare case of diabetic ketosis with movement disorder in a young
      patient.

PMID- 22416166
TI  - Bilateral dacryoadenitis.
AB  - Acute dacryoadenitis is an uncommon condition that involves inflammation of the
      lacrimal gland. In rare instances, dacryoadenitis may be bilateral. A delay in
      proper treatment of an otherwise simple case of dacryoadenitis may lead to
      significant soft tissue morbidity such as cellulitis, lacrimal gland abscess, or
      orbital abscess. We report the case of a 24-year-old male who presented to the
      emergency department with acute bilateral dacryoadenitis. The patient's symptoms
      did not respond to oral antibiotics and he subsequently required admission for
      intravenous antibiotics. During his hospitalization the patient had diagnostic
      testing to try to determine the etiology for his symptoms. The unique aspects of
      managing a case of bilateral dacryoadenitis as well as treatment recommendations
      are discussed in this case report.

PMID- 22416168
TI  - Broken tracheostomy tube: A fractured mandate.
AB  - Tracheostomy is a common airway procedure for life support. This procedure is
      safe, although occasional early and late complications are known to occur.
      Fracture and hence aspiration of a tracheostomy tube in the tracheobronchial tree
      is a rare late complication, which can be potentially life threatening. Published
      reports of a fractured tracheostomy tube presenting as a foreign body in the
      tracheobronchial tree are few. The most common dislodged sites reported were the
      trachea and the right main bronchus, the inner flange in our patient was lodged
      in the trachea and the left main bronchus. Foreign-body aspiration is a serious
      medical emergency demanding timely recognition and prompt action as was
      successfully done in our patient. Therapeutic rigid bronchoscopic removal is the
      mainstay of treatment. A periodic review of the techniques of tracheostomy care
      including timely check-ups for signs of wear and tear can possibly eliminate such
      avoidable late complications.

PMID- 22416167
TI  - An unusual differential for a pulseless trauma patient.
AB  - Hemorrhagic shock is the most common reason to explain the inability to feel
      pulse in a trauma patient. However, clinicians should always suspect atypical
      causes for differential pulses in this population and Takayasu's arteritis (TA)
      is one such example. We report a case of aorto-arteritis in a patient who
      presented with trauma and was later diagnosed with TA. She had blood pressure
      discrepancy between upper and lower limbs noted upon her initial trauma
      evaluation.

PMID- 22416169
TI  - Hemoperitoneum from splenic rupture in an expatriate.
AB  - Splenic rupture with hemoperitoneum represents a life-threatening surgical
      emergency. Malaria should be highly suspected as the probable underlying disease
      in returning travellers, expatriates, or recent immigrants from endemic
      countries. Malarial complications involving the spleen occur even with
      appropriate prophylaxis or during antimalarial therapy. Among them, splenic
      infarction has a favourable course and is treated conservatively, whereas life
      threatening rupture requires immediate or delayed splenectomy. Computed
      tomography (CT) allows confident differentiation between these two complications
      by identifying ruptured spleen with clotted hematoma and associated high-density
      peritoneal effusion; furthermore, CT allows differential diagnosis from other
      causes of spontaneous hemoperitoneum.

PMID- 22416170
TI  - Cerebral microdialysis and PtiO2 to decide unilateral decompressive craniectomy
      after brain gunshot.
AB  - Decompressive craniectomy (DC) following brain injury can induce complications
      (hemorrhage, infection, and hygroma). It is then considered as a last-tier
      therapy, and can be deleteriously delayed. Focal neuromonitoring (microdialysis
      and PtiO2) can help clinicians to decide bedside to perform DC in case of
      intracranial pressure (ICP) around 20 to 25 mmHg despite maximal medical
      treatment. This was the case of a hunter, brain injured by gunshot. DC was
      performed at day 6, because of unstable ICP, ischemic trend of PtiO2, and
      decreased cerebral glucose but normal lactate/pyruvate ratio. His evolution was
      good despite left hemiplegia due to initial injury.

PMID- 22416171
TI  - Improvized management of lumbar disc prolapse in Antarctica.

PMID- 22416172
TI  - Need for encouraging translational research in India.

PMID- 22416173
TI  - Radiofrequency ablation or percutaneous ethanol injection for the treatment of
      liver tumors.
AB  - The liver is a common location of both primary and secondary malignancies. For
      unresectable liver cancer, many local ablative therapies have been developed.
      These include e.g., percutaneous ethanol injection (PEI), percutaneous acetic
      acid injection, radiofrequency ablation (RFA), cryoablation, microwave ablation,
      laser-induced thermotherapy, and high-intensity focused ultrasound. RFA has
      recently gained interest and is the most widely applied thermoablative technique.
      RFA allows more effective tumor control in fewer treatment sessions compared with
      PEI, but with a higher rate of complications. However, there are certain
      circumstances where PEI therapy represents a better strategy to control liver
      tumors than RFA, especially in situations where RFA is difficult, for example
      when large vessels surround the tumor. In the context of hepatocellular carcinoma
      (HCC), both RFA and PEI are feasible and of benefit in non-operable patients. RFA
      seems superior to PEI in HCC > 2 cm, and the combination of interventions may be
      of benefit in selected patients. Liver resection is superior to RFA for patients
      with HCC meeting the Milan criteria, but RFA can be employed in tumors <= 3 cm
      and where there is an increased expected operative mortality. In addition, some
      lines of evidence indicate that RFA and PEI can be employed as a bridge to liver
      transplantation. The use of RFA in colorectal liver metastases is currently
      limited to unresectable disease and for patients unfit for surgery. The aim of
      this article is to summarize the current status of RFA in the management of liver
      tumors and compare it to the cheap and readily available technique of PEI.

PMID- 22416174
TI  - Neuroendocrine liver metastases: contributions of endoscopy and surgery to
      primary tumor search.
AB  - Neuroendocrine tumors (NETs) are diagnosed with increasing frequency and patients
      often present with liver metastases at the time of diagnosis. Apart from
      treatment of the metastases, resection of the primary tumor at an early phase is
      recommended to prevent complications, although it may be difficult to locate,
      especially in patients with functionally inactive NETs. Small and multifocal
      tumors in the jejunum and ileum represent a particular challenge. Primary hepatic
      neuroendocrine carcinoma is extremely rare and is diagnosed only after exclusion
      of other primary tumors. Therefore, some uncertainty may remain, as small non
      hepatic primary tumors may escape detection. Diagnostic work-up in these patients
      includes biochemical assays and imaging modalities (also comprising specific
      techniques of scintigraphy and positron emission tomography). This editorial
      highlights the contributions of endoscopy and operative exploration to the search
      for the primary tumor. Besides esophago-gastro-duodenoscopy, endoscopic
      ultrasonography, colonoscopy and bronchoscopy, special endoscopic techniques such
      as balloon enteroscopy or capsule endoscopy are used with growing experience.
      Compared with balloon enteroscopy, capsule endoscopy is non-invasive and better
      tolerated, but it cannot localize a lesion precisely and does not allow biopsy or
      removal of lesions. Before proceeding to surgery, a discussion of the findings by
      a tumor board should be a standard procedure. Improvements in diagnostic tools
      have created new perspectives for the detection of obscure primary tumors in
      patients with neuroendocrine liver metastases, and these searches are best
      coordinated by a multidisciplinary team.

PMID- 22416175
TI  - Strategy to differentiate autoimmune pancreatitis from pancreas cancer.
AB  - Autoimmune pancreatitis (AIP) is a newly described entity of pancreatitis in
      which the pathogenesis appears to involve autoimmune mechanisms. Based on
      histological and immunohistochemical examinations of various organs of AIP
      patients, AIP appears to be a pancreatic lesion reflecting a systemic "IgG4
      related sclerosing disease". Clinically, AIP patients and patients with
      pancreatic cancer share many features, such as preponderance of elderly males,
      frequent initial symptom of painless jaundice, development of new-onset diabetes
      mellitus, and elevated levels of serum tumor markers. It is of uppermost
      importance not to misdiagnose AIP as pancreatic cancer. Since there is currently
      no diagnostic serological marker for AIP, and approach to the pancreas for
      histological examination is generally difficult, AIP is diagnosed using a
      combination of clinical, serological, morphological, and histopathological
      features. Findings suggesting AIP rather than pancreatic cancer include:
      fluctuating obstructive jaundice; elevated serum IgG4 levels; diffuse enlargement
      of the pancreas; delayed enhancement of the enlarged pancreas and presence of a
      capsule-like rim on dynamic computed tomography; low apparent diffusion
      coefficient values on diffusion-weighted magnetic resonance image; irregular
      narrowing of the main pancreatic duct on endoscopic retrograde
      cholangiopancreatography; less upstream dilatation of the main pancreatic duct on
      magnetic resonance cholangiopancreatography, presence of other organ involvement
      such as bilateral salivary gland swelling, retroperitoneal fibrosis and hilar or
      intrahepatic sclerosing cholangitis; negative work-up for malignancy including
      endoscopic ultrasound-guided fine needle aspiration; and steroid responsiveness.
      Since AIP responds dramatically to steroid therapy, accurate diagnosis of AIP can
      avoid unnecessary laparotomy or pancreatic resection.

PMID- 22416176
TI  - Botulinum toxin for chronic anal fissure after biliopancreatic diversion for
      morbid obesity.
AB  - AIM: To study the effect of botulinum toxin in patients with chronic anal fissure
      after biliopancreatic diversion (BPD) for severe obesity. METHODS: Fifty-nine
      symptomatic adults with chronic anal fissure developed after BPD were enrolled in
      an open label study. The outcome was evaluated clinically and by comparing the
      pressure of the anal sphincters before and after treatment. All data were
      analyzed in univariate and multivariate analysis. RESULTS: Two months after
      treatment, 65.4% of the patients had a healing scar. Only one patient had mild
      incontinence to flatus that lasted 3 wk after treatment, but this disappeared
      spontaneously. In the multivariate analysis of the data, two registered months
      after the treatment, sex (P = 0.01), baseline resting anal pressure (P = 0.02)
      and resting anal pressure 2 mo after treatment (P < 0.0001) were significantly
      related to healing rate. CONCLUSION: Botulinum toxin, despite worse results than
      in non-obese individuals, appears the best alternative to surgery for this group
      of patients with a high risk of incontinence.

PMID- 22416177
TI  - 15-PGDH is reduced and induces apoptosis and cell cycle arrest in gastric
      carcinoma.
AB  - AIM: To investigate the expression of 15-hydroxyprostaglandin dehydrogenase (15
      PGDH) in human gastric cancer and it's mechanism in apoptosis and cell cycle
      arrest. METHODS: Expression of 15-PGDH mRNA and protein was examined by
      immunohistochemistry, immunocytochemistry, reverse transcriptase polymerase chain
      reaction (RT-PCR) and Western blotting in tissue from human gastric cancer,
      gastric precancerous state (gastric polyps and atrophic gastritis), normal
      stomach, and gastric cancer cell lines. The relationship between gastric cancer,
      gastric precancerous state and 15-PGDH expression was determined. The association
      between expression of 15-PGDH and various clinicopathological parameters in
      gastric cancer was evaluated. Human gastric cancer cell line SGC-7901 was
      transfected with 15-PGDH expression plasmids. The effect of 15-PGDH on the cell
      cycle was examined by flow cytometry. The effect of 15-PGDH on apoptosis was
      examined by transmission electron microscopy, flow cytometry and transferase
      mediated nick end labeling (TUNEL) assay. Expression of cell cycle (p21, p27, p16
      and p53) and apoptosis (Survivin, BCL-2, BCL-X(L), BAK and BAX) genes was
      analyzed by RT-PCR. RESULTS: Expression of 15-PGDH mRNA and protein in human
      gastric cancer tissues was significantly lower than in normal gastric tissues (P
      < 0.01). Expression in human gastric cancer cell lines MKN-28 and MKN-45 was
      reduced, and absent in SGC-7901 cells (P < 0.05). Reduction of 15-PGDH expression
      was also found in precancerous tissues, such as gastric polyps and atrophic
      gastritis (P < 0.01). There was a significant difference in expression of 15-PGDH
      among various gastric cancer pathological types (P < 0.05), with or without
      distant metastasis (P < 0.05) and different TNM stage (P < 0.01). Flow cytometry
      demonstrated a significant increase in apoptotic cells in SGC-7901 cells
      transfected with pcDNA3/15-PGDH plasmid for 24 h and 48 h (P < 0.01), and an
      increased fraction of sub-G1 phase after transfection (P < 0.05). TUNEL assay
      showed an increased apoptotic index in cells overexpressing 15-PGDH (P < 0.01).
      After transfection, expression of proapoptotic genes, such as BAK (P < 0.05), BAX
      and p53 (P < 0.01), was increased. Expression of antiapoptotic genes was
      decreased, such as Survivin, BCL-2 and BCL-X(L) (P < 0.01). Expression of cyclin
      dependent kinase inhibitors p21 and p16 (P < 0.01) was significantly upregulated
      in cells overexpressing 15-PGDH. CONCLUSION: Reduction of 15-PGDH is associated
      with carcinogenesis and development of gastric carcinoma. 15-PGDH induces
      apoptosis and cell cycle arrest in SGC-7901 cells.

PMID- 22416178
TI  - Chronic bile duct hyperplasia is a chronic graft dysfunction following liver
      transplantation.
AB  - AIM: To investigate pathological types and influential factors of chronic graft
      dysfunction (CGD) following liver transplantation (LT) in rats. METHODS: The
      whole experiment was divided into three groups: (1) normal group (n = 12): normal
      BN rats without any drug or operation; (2) syngeneic transplant group (SGT of BN
      BN, n = 12): both donors and recipients were BN rats; and (3) allogeneic
      transplant group (AGT of LEW-BN, n = 12): Donors were Lewis and recipients were
      BN rats. In the AGT group, all recipients were subcutaneously injected by
      Cyclosporin A after LT. Survival time was observed for 1 year. All the dying rats
      were sampled, biliary tract tissues were performed bacterial culture and liver
      tissues for histological study. Twenty-one day after LT, 8 rats were selected
      randomly in each group for sampling. Blood samples from caudal veins were
      collected for measurements of plasma endotoxin, cytokines and metabonomic
      analysis, and faeces were analyzed for intestinal microflora. RESULTS: During the
      surgery of LT, no complications of blood vessels or bile duct happened, and all
      rats in each group were still alive in the next 2 wk. The long term observation
      revealed that a total of 8 rats in the SGT and AGT groups died of hepatic graft
      diseases, 5 rats in which died of chronic bile duct hyperplasia. Compared to the
      SGT and normal groups, survival ratio of rats significantly decreased in the AGT
      group (P < 0.01). Moreover, liver necrosis, liver infection, and severe chronic
      bile duct hyperplasia were observed in the AGT group by H and E stain. On 21 d
      after LT, compared with the normal group (25.38 +/- 7.09 ng/L) and SGT group
      (33.12 +/- 10.26 ng/L), plasma endotoxin in the AGT group was remarkably
      increased (142.86 +/- 30.85 ng/L) (both P < 0.01). Plasma tumor necrosis factor
      alpha and interleukin-6 were also significantly elevated in the AGT group (593.6
      +/- 171.67 pg/mL, 323.8 +/- 68.30 pg/mL) vs the normal (225.5 +/- 72.07 pg/mL,
      114.6 +/- 36.67 pg/mL) and SGT groups (321.3 +/- 88.47 pg/mL, 205.2 +/- 53.06
      pg/mL) (P < 0.01). Furthermore, Bacterial cultures of bile duct tissues revealed
      that the rats close to death from the SGT and AGT groups were strongly positive,
      while those from the normal group were negative. The analysis of intestinal
      microflora was performed. Compared to the normal group (7.98 +/- 0.92, 8.90 +/-
      1.44) and SGT group (8.51 +/- 0.46, 9.43 +/- 0.69), the numbers of Enterococcus
      and Enterobacteria in the AGT group (8.76 +/- 1.93, 10.18 +/- 1.64) were
      significantly increased (both P < 0.01). Meanwhile, compared to the normal group
      (9.62 +/- 1.60, 9.93 +/- 1.10) and SGT group (8.95 +/- 0.04, 9.02 +/- 1.14), the
      numbers of Bifidobacterium and Lactobacillus in the AGT group (7.83 +/- 0.72,
      8.87 +/- 0.13) were remarkably reduced (both P < 0.01). In addition, metabonomics
      analysis showed that metabolic profiles of plasma in rats in the AGT group were
      severe deviated from the normal and SGT groups. CONCLUSION: Chronic bile duct
      hyperplasia is a pathological type of CGD following LT in rats. The mechanism of
      this kind of CGD is associated with the alterations of inflammation, intestinal
      barrier function and microflora as well as plasma metabolic profiles.

PMID- 22416179
TI  - Intravenous injection of mesenchymal stem cells is effective in treating liver
      fibrosis.
AB  - AIM: To compare the influence of different transplant sites in bone marrow
      mesenchymal stem cell (MSC)-based therapy for liver fibrosis. METHODS: MSCs
      isolated from Sprague Dawley (SD) rats were induced into hepatocyte-like cells.
      Liver fibrosis in SD rats was induced with carbon tetrachloride. Following
      hepatocyte induction in vitro, 4',6-diamidino-2-phenylindole (DAPI)-labeled MSCs
      were transplanted by intravenous, intrahepatic, and intraperitoneal injection.
      Histopathological staining, immunohistochemistry, and biochemical analysis were
      used to compare the morphological and functional liver regeneration among
      different MSC injection modalities. The expression differences of interleukins,
      growth factor, extracellular matrix, matrix metalloproteinases, and tissue
      inhibitor of metalloproteinase were examined by real-time reverse transcription
      polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA).
      RESULTS: Four days after exposure to hepatocyte differentiation medium, MSCs that
      did not express hepatocyte markers could express alpha-fetoprotein, albumin, and
      cytokeratin 18. The results of histopathological staining, immunohistochemistry,
      and biochemical analysis indicated that intravenous injection is more effective
      at rescuing liver failure than other injection modalities. DAPI-labeled cells
      were found around liver lobules in all three injection site groups, but the
      intravenous group had the highest number of cells. PCR and ELISA analysis
      indicated that interleukin-10 (IL-10) was highest in the intravenous group,
      whereas il1beta, il6, tnfalpha and tgfbeta, which can be regulated by IL10 and
      are promoters of liver fibrosis, were significantly lower than in the other
      groups. CONCLUSION: MSC administration is able to protect against liver fibrosis.
      Intravenous injection is the most favorable treatment modality through promotion
      of IL10 expression.

PMID- 22416180
TI  - Rebamipide suppresses diclofenac-induced intestinal permeability via
      mitochondrial protection in mice.
AB  - AIM: To investigate the protective effect and mechanism of rebamipide on small
      intestinal permeability induced by diclofenac in mice. METHODS: Diclofenac (2.5
      mg/kg) was administered once daily for 3 d orally. A control group received the
      vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered
      intragastrically once a day for 3 d 4 h after diclofenac administration.
      Intestinal permeability was evaluated by Evans blue and the FITC-dextran method.
      The ultrastructure of the mucosal barrier was evaluated by transmission electron
      microscopy (TEM). Mitochondrial function including mitochondrial swelling,
      mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide
      reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were
      measured. Small intestinal mucosa was collected for assessment of malondialdehyde
      (MDA) content and myeloperoxidase (MPO) activity. RESULTS: Compared with the
      control group, intestinal permeability was significantly increased in the
      diclofenac group, which was accompanied by broken tight junctions, and
      significant increases in MDA content and MPO activity. Rebamipide significantly
      reduced intestinal permeability, improved inter-cellular tight junctions, and was
      associated with decreases in intestinal MDA content and MPO activity. At the
      mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level
      and decreased mitochondrial swelling. CONCLUSION: Increased intestinal
      permeability induced by diclofenac can be attenuated by rebamipide, which
      partially contributed to the protection of mitochondrial function.

PMID- 22416181
TI  - Differential diagnosis in patients with suspected bile acid synthesis defects.
AB  - AIM: To investigate the clinical presentations associated with bile acid
      synthesis defects and to describe identification of individual disorders and
      diagnostic pitfalls. METHODS: Authors describe semiquantitative determination of
      16 urinary bile acid metabolites by electrospray ionization-tandem mass
      spectrometry. Sample preparation was performed by solid-phase extraction. The
      total analysis time was 2 min per sample. Authors determined bile acid
      metabolites in 363 patients with suspected defects in bile acid metabolism.
      RESULTS: Abnormal bile acid metabolites were found in 36 patients. Two patients
      had bile acid synthesis defects but presented with atypical presentations. In 2
      other patients who were later shown to be affected by biliary atresia and cystic
      fibrosis the profile of bile acid metabolites was initially suggestive of a bile
      acid synthesis defect. Three adult patients suffered from cerebrotendinous
      xanthomatosis. Nineteen patients had peroxisomal disorders, and 10 patients had
      cholestatic hepatopathy of other cause. CONCLUSION: Screening for urinary
      cholanoids should be done in every infant with cholestatic hepatopathy as well as
      in children with progressive neurological disease to provide specific therapy.

PMID- 22416182
TI  - Evaluation of acoustic radiation force impulse imaging for determination of liver
      stiffness using transient elastography as a reference.
AB  - AIM: To evaluate cut-off values and performance of acoustic radiation force
      impulse imaging (ARFI) using transient elastography [FibroScan(c) (FS)] as a
      reference. METHODS: Six hundred and six patients were enrolled in this study. All
      patients underwent liver stiffness measurement with FS (FS-LS) and ARFI (with
      shear wave velocity quantification; ARFI-SWV) and the performance of ARFI in
      comparison to FS was determined. Sixty-eight patients underwent liver biopsy.
      RESULTS: Significantly higher success rates for the determination of liver
      stiffness were found using ARFI as compared to FS [604/606 (99.7%) vs. 482/606
      (79.5%), P < 0.001]. ARFI-SWV correlated significantly with FS-LS (r = 0.920, P <
      0.001). ARFI-SWV increased significantly with the stage of fibrosis (1.09 +/-
      0.13 m/s for patients with no significant fibrosis (FS-LS < 7.6 kPa); 1.46 +/-
      0.27 m/s for patients with significant liver fibrosis (7.6 < FS-LS <= 13.0 kPa);
      and 2.55 +/- 0.77 m/s for patients with liver cirrhosis (FS-LS > 13.0 kPa)). ARFI
      SWV cut-off values were identified for no significant fibrosis (1.29 m/s;
      sensitivity 91.4% and specificity 92.6%) and for liver cirrhosis (1.60 m/s;
      sensitivity 92.3% and specificity 96.5%). The optimal cut-off value for
      predicting liver fibrosis (F >= 2) was 1.32 m/s (sensitivity 87.0% and
      specificity 80.0%) and for liver cirrhosis (F4) 1.62 m/s (sensitivity 100% and
      specificity 85.7%), for patients who underwent liver biopsy. An excellent inter
      and intraobserver reproducibility was observed for ARFI-SWV determinations.
      CONCLUSION: An ARFI-SWV cut-off value of 1.29 m/s seems to be optimal for
      patients with no significant liver fibrosis and 1.60 m/s for patients with liver
      cirrhosis.

PMID- 22416183
TI  - Framework for assessing quality of care for inflammatory bowel disease in Sweden.
AB  - AIM: To create and apply a framework for quality assessment and improvement in
      care for inflammatory bowel disease (IBD) patients. METHODS: A framework for
      quality assessment and improvement was created for IBD based on two generally
      acknowledged quality models. The model of Donabedian (Df) offers a logistical and
      productive perspective and the Clinical Value Compass (CVC) model adds a
      management and service perspective. The framework creates a pedagogical tool to
      understand the balance between the dimensions of clinical care (CVC) and the
      components of clinical outcome (Df). The merged models create a framework of the
      care process dimensions as a whole, reflecting important parts of the IBD care
      delivery system in a local setting. Clinical and organizational quality measures
      were adopted from clinical experience and the literature and were integrated into
      the framework. Data were collected at the yearly check-up for 481 IBD patients
      during 2008. The application of the quality assessment framework was tested and
      evaluated in a local clinical IBD care setting in Jonkoping County, Sweden.
      RESULTS: The main outcome was the presentation of how locally-selected clinical
      quality measures, integrated into two complementary models to develop a
      framework, could be instrumental in assessing the quality of care delivered to
      patients with IBD. The selected quality measures of the framework noted less
      anemia in the population than previously reported, provided information about
      hospitalization rates and the few surgical procedures reported, and noted good
      access to the clinic. CONCLUSION: The applied local quality framework was
      feasible and useful for assessing the quality of care delivered to IBD patients
      in a local setting.

PMID- 22416184
TI  - Autoimmune thyroid diseases and Helicobacter pylori: the correlation is present
      only in Graves's disease.
AB  - AIM: To investigate the correlation between autoimmune thyroid diseases (ATDs)
      and the prevalence of Cag-A positive strains of Helicobacter pylori (H. pylori)
      in stool samples. METHODS: Authors investigated 112 consecutive Caucasian
      patients (48 females and 4 males with Graves' disease and 54 females and 6 males
      with Hashimoto's thyroiditis HT), at their first diagnosis of ATDs. Authors
      tested for H. pylori in stool samples using an amplified enzyme immunoassay and
      Cag-A in serum samples using an enzyme-linked immunoassay method (ELISA). The
      results were analyzed using the two-sided Fisher's exact test and the respective
      odds ratio (OR) was calculated. RESULTS: A marked correlation was found between
      the presence of H. pylori (P <= 0.0001, OR 6.3) and, in particular, Cag-A
      positive strains (P <= 0.005, OR 5.3) in Graves' disease, but not in Hashimoto's
      thyroiditis, where authors found only a correlation with Cag-A strains (P <=
      0.005, OR 8.73) but not when H. pylori was present. CONCLUSION: The marked
      correlation between H. pylori and Cag-A, found in ATDs, could be dependent on the
      different expression of adhesion molecules in the gastric mucosa.

PMID- 22416185
TI  - Predictability of outcome of caustic ingestion by esophagogastroduodenoscopy in
      children.
AB  - AIM: To assess the necessity of esophagogastroduodenoscopy (EGD) to predict the
      outcome of caustic ingestion in children. METHODS: The study included 206
      children who underwent EGD because of ingestion of caustic substances between
      January 2005 and August 2010. Retrospective analysis of data of the patients was
      performed. RESULTS: The male/female ratio was 1.6 and mean age was 38.1 +/- 28.8
      mo. The caustic substances were acidic in 72 (34.9%) cases, alkaline in 56
      (27.2%), liquid household bleach in 62 (30.1%), and unknown in 16 (7.8%). Fifty
      seven (27.7%) patients were symptom-free. Significant clinical findings were
      observed in 149 (72.3%) patients. Upper gastrointestinal endoscopy findings of
      esophageal injury were grade 0 in 86 (41.7%) patients, grade 1 in 49 (23.8%),
      grade 2a in 42 (20.4%), grade 2b in 28 (13.6%), and grade 3a in 1 (0.5%) patient.
      35 patients with grade 2a, 2b, and 3a injuries underwent esophageal dilation at
      second week of ingestion. Esophageal stricture, which necessitated a regular
      dilation program developed in 13 of the aforementioned 35 patients. There is no
      statistically significant difference in the rate of development of esophageal
      stricture between the patients who ingested acidic (15.3%) and alkaline (8.9%)
      substances (P = 0.32). Severe gastric injury was detected in 38 (18.5%) patients.
      The rate of development of gastric injury was significantly higher in the acidic
      group (14%) than in the alkaline group (2.9%) (P = 0.001). Out of 149 patients
      with clinical findings, 49 (32.9%) patients had no esophageal injury and 117
      (78.5%) patients had no gastric lesion. Esophageal and severe gastric injuries
      were detected in 20 (35.1%) and 8 (14%) of patients with no clinical findings
      respectively. Pyloric stenosis developed in 6 patients. Pyloric obstruction
      improved with balloon dilation in 2 patients. Mean hospitalization time were 1.2
      +/- 0.5 d for grade 0 and 2.3 +/- 5 d for grade 1 and 6.3 +/- 6.2 d for grade 2a
      and 15.8 +/- 18.6 d for grade 2b. It was significantly longer for patients with
      grade 2a and 2b injuries (P = 0.000). CONCLUSION: Endoscopy is an effective
      technique for determining the presence of esophageal and gastric damage and to
      avoid unnecessary treatment in patients with no or mild injury.

PMID- 22416186
TI  - Bevacizumab as a second- or later-line of treatment for metastatic colorectal
      cancer.
AB  - AIM: To determine the efficacy of bevacizumab in patients with metastatic
      colorectal cancer (MCRC) who have failed prior chemotherapy without bevacizumab.
      METHODS: Between March 2002 and June 2010, 40 patients in South Korea with MCRC
      who were treated with bevacizumab plus chemotherapy as a second or later-line
      treatment were analyzed retrospectively for their overall response rate (ORR),
      overall survival (OS), and progression-free survival (PFS). The tumor responses
      were assessed using the Response Evaluation Criteria in Solid Tumors guidelines.
      RESULTS: All of the patients had progressed under prior chemotherapy without
      bevacizumab. Three patients (7.5%) exhibited an ORR, twenty one patients (52.5%)
      exhibited stable disease (SD), and fifteen patients (37.5%) exhibited disease
      progression. The median duration of the OS and PFS were 14.0 mo and 6.13 mo
      respectively. The median OSs were 16.60, 14.07 and 13.00 mo for second-line,
      third-line and fourth- or later-line treatments, respectively. The median PFSs
      were 7.23, 7.30 and 3.87 mo for the second-line, third-line and fourth- or later
      line treatments, respectively. CONCLUSION: In patients with MCRC, bevacizumab
      combined chemotherapy may be beneficial during second- or later-line treatment.

PMID- 22416187
TI  - Is hepatic neoplasm-related pyogenic liver abscess a distinct clinical entity?
AB  - AIM: To compare the clinical characteristics of pyogenic liver abscess (PLA) in
      patients with and without hepatic neoplasm (HN). METHODS: Authors performed a
      retrospective analysis involving patients with PLA. The demographic, clinical
      features, laboratory and imaging findings, management and outcome of patients
      with and without HN were studied. RESULTS: From January 2000 to December 2009
      inclusive, 318 patients (35 with HN) had PLA, and mean age and comorbidity were
      comparable between the two groups. More patients with HN experienced right upper
      quadrant pain (68.6% vs. 52.7%, P < 0.04), developed jaundice (14.3% vs. 5.7%, P
      < 0.03) and hepatomegaly (17.1% vs. 3.9%, P < 0.01), and had higher serum total
      bilirubin level (43.3 MUmol/L vs. 30.0 MUmol/L, P = 0.05). Most patients in both
      groups had PLAs in the right hepatic lobe, and biliary tract disorder was the
      most common underlying cause (71.4% and 61.8%). However, more PLAs in the HN
      group were associated with thicker abscess wall (37.1% vs. 19.4%, P < 0.01),
      septal lobulation (77.1% vs. 58%, P < 0.02), gaseous cavitation (17% vs. 7.8%, P
      = 0.03), portal thrombophlebitis (11.4% vs. 1.8%, P < 0.01) and aerobilia (25.9%
      vs. 5.5%, P < 0.01). Mixed bacterial growth (40% vs. 15.2%, P < 0.01) and Gram
      negative bacilli (22.8% vs. 60.4%, P < 0.01) were dominant isolates in PLAs with
      and without HN, respectively. Although incidence of the complications was
      comparable between the two groups, patients with HN had a higher mortality rate
      than those without (71.4% vs. 8.8%, P < 0.01). Multivariate logistic regression
      analysis revealed underlying active malignancy [odds ratio (OR): 40.45, 95% CI:
      14.76-111.65], hypoalbuminemia (OR: 1.22, 95% CI: 1.14-1.38), disseminated
      intravascular coagulation (OR: 3.32, 95% CI: 1.19-9.69) and acute coronary
      syndrome (OR: 4.48, 95% CI: 1.08-17.8) were independent risk factors associated
      with mortality. However, several HN cases, presented concurrently with PLAs, were
      found to have curative resectable tumors and had good prognosis after surgery.
      CONCLUSION: PLA associated with HN tends to form a distinct clinical syndrome
      with a different extent of clinical manifestations, radiological and
      microbiological features and complications.

PMID- 22416188
TI  - Association between gastric cancer and -1993 polymorphism of TBX21 gene.
AB  - AIM: To investigate the association between the polymorphism of TBX21 gene and
      the risk of gastric cancer in a Chinese population. METHODS: The -1993
      polymorphism located in TBX21 gene promoter region was identified by polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The
      risk between TBX21 gene genotype and gastric cancer was determined by
      multivariate logistic regression analysis in 220 gastric cancer patients and 262
      cancer-free controls matched by age, sex and ethnicity. RESULTS: Compared with
      the TBX21 -1993TT genotype, the -1993CC genotype exhibited a significantly
      elevated risk for gastric cancer [Odds ratio (OR) = 3.42, 95% confidence interval
      (CI): 1.41-8.31]. The relationship between the -1993 polymorphic genotype and the
      invasive status such as lymph node and distant metastasis was found among the
      gastric cancer patients (OR = 4.02, 95% CI: 1.87-8.66; OR = 7.02, 95% CI: 3.44
      14.34, respectively). CONCLUSION: TBX21 -1993 polymorphism might contribute to
      the risk of gastric cancer, especially to the distant metastasis.

PMID- 22416189
TI  - Interleukin-8, a promising predictor for prognosis of pancreatic cancer.
AB  - AIM: To investigate the value of interleukin-8 (IL-8), a pro-inflammatory
      chemokine, in predicting the prognosis of pancreatic cancer. METHODS: Expression
      of IL-8 and its receptor CXCR1 was assessed by immunohistochemistry in pancreatic
      cancer and chronic pancreatitis samples. Enzyme-linked immunosorbent assay was
      used to detect the serum IL-8 levels in pancreatic cancer patients. Human
      pancreatic cancer tissues were heterotopically transplanted to the immune
      deficiency mice to evaluate the effect of serum IL-8 on the tumorigenesis of the
      cancer samples. RESULTS: IL-8 and CXCR1 proteins were both over-expressed in
      pancreatic adenocarcinoma samples (55.6% and 65.4%, respectively) compared with
      the matched para-cancer tissues (25.9% and 12.3%, P < 0.01), or chronic
      pancreatitis (0% and 25%, P < 0.05). Serum IL-8 levels in pancreatic cancer
      patients (271.1 +/- 187.7 ng/mL) were higher than in other digestive system
      tumors, such as gastric cancer (41.77 +/- 9.11 ng/mL, P = 0.025), colorectal
      carcinoma (78.72 +/- 80.60 ng/mL, P = 0.032) and hepatocellular carcinoma (59.60
      +/- 19.80 ng/mL, P = 0.016). In vivo tumorigenesis analysis further proved that
      tumor tissues from patients with higher serum IL-8 levels grew faster than those
      with lower IL-8 levels. CONCLUSION: IL-8 can be a fine serum marker for
      predicting the prognosis pancreatic cancer.

PMID- 22416190
TI  - Quantification of choline concentration following liver cell apoptosis using 1H
      magnetic resonance spectroscopy.
AB  - AIM: To evaluate the feasibility of quantifying liver choline concentrations in
      both normal and apoptotic rabbit livers in vivo, using 1H magnetic resonance
      spectroscopy (1H-MRS). METHODS: 1H-MRS was performed in 18 rabbits using a 1.5T
      GE MR system with an eight-channel head/neck receiving coil. Fifteen rabbits were
      injected with sodium selenite at a dose of 10 MUmol/kg to induce the liver cell
      apoptosis. Point-resolved spectroscopy sequence-localized spectra were obtained
      from 10 livers once before and once 24 h after sodium selenite injection in vivo.
      T1 and T2 relaxation time of water and choline was measured separately in the
      livers of three healthy rabbits and three selenite-treated rabbits. Hematoxylin
      and eosin and dUTP-biotin nick end labeling (TUNEL) staining was used to detect
      and confirm apoptosis. Choline peak areas were measured relative to unsuppressed
      water using LCModel. Relaxation attenuation was corrected using the average of T1
      and T2 relaxation time. The choline concentration was quantified using a formula,
      which was tested by a phantom with a known concentration. RESULTS: Apoptosis of
      hepatic cells was confirmed by TUNEL assay. In phantom experiment, the choline
      concentration (3.01 mmol/L), measured by 1H-MRS, was in good agreement with the
      actual concentration (3 mmol/L). The average T1 and T2 relaxation time of choline
      was 612 +/- 15 ms and 74 +/- 4 ms in the control group and 670 +/- 27 ms and 78
      +/- 5 ms in apoptotic livers in vivo, respectively. Choline was quantified in 10
      rabbits, once before and once after the injection with sodium selenite. The
      choline concentration decreased from 14.5 +/- 7.57 mmol/L before sodium selenite
      injection to 10.8 +/- 6.58 mmol/L (mean +/- SD, n = 10) after treatment (Z = 
      2.395, P < 0.05, two-sample paired Wilcoxon test). CONCLUSION: 1H-MRS can be used
      to quantify liver choline in vivo using unsuppressed water as an internal
      reference. Decreased liver choline concentrations are found in sodium selenite
      treated rabbits undergoing liver cell apoptosis.

PMID- 22416191
TI  - Large-vessel thrombosis in intestinal Behcet's disease complicated with
      myelodysplastic syndrome and trisomy 8.
AB  - Behcet's disease is characterized by recurrent oral ulcers, genital ulcers,
      uveitis and skin lesions. Myelodysplastic syndrome (MDS) is characterized by
      problems due to ineffective hematopoiesis. Several studies have identified a
      relationship between MDS and Behcet's disease, especially intestinal Behcet's
      disease. Trisomy 8 seems to play an important role in these disorders as well.
      The present case was a 24-year-old woman who had a huge tonsil ulcer with initial
      symptoms of odynophagia and intermittent fever. We also noted folliculitis on her
      upper back. Five days later, she began to experience diarrhea and abdominal pain.
      Abdominal computed tomography and subsequent surgery revealed ileum perforation
      and enterocolitis with multiple ulcers. Later, she was admitted again for a
      vulvar suppurative ulcer and suspicious Bartholin's cyst infection. The patient's
      clinical presentations met the criteria for Behcet's disease. Six months after
      the bowel perforation event, we noted the development of pancytopenia in a
      routine laboratory examination. All the examinations led to the diagnosis of MDS
      with trisomy 8. The most unusual finding was that multiple large vessel thrombi
      developed during follow-up. Previous studies have suggested that trisomy 8 in MDS
      leads to concurrent intestinal Behcet's disease. Moreover, the inflammatory and
      immune genes related to thrombus formation are overexpressed in cases of MDS with
      trisomy 8. Trisomy 8 must play a role in thrombosis. Further studies are needed
      to help clarify the pathophysiology and pathogenesis of these disorders.

PMID- 22416192
TI  - The Canadian Journal of Infectious Diseases and The Canadian Infectious Disease
      Society - New beginnings, at the right time.

PMID- 22416193
TI  - Office diagnosis of pertussis.

PMID- 22416194
TI  - Resurgence of virulent group A streptococcal infections - the streptococcal toxic
      shock syndrome.

PMID- 22416195
TI  - The search for Ixodes dammini and Borrelia burgdorferi in Nova Scotia.
AB  - Twenty-four Ixodes dammini ticks (23 adults and one nymph) have been recovered in
      Nova Scotia since 1984. There has not been a systematic search for larvae and
      none has been identified. The recovery of the nymph from a road-killed yellow
      throat bird, Geothypis trichas, in late May 1990 supports the contention that
      migrating birds are bringing deer ticks into the province every spring. In March
      and April 1991, four adult deer ticks were identified, suggesting that these
      ticks had overwintered. These deer tick specimens indicate that it is possible
      that I dammini is becoming established in Nova Scotia, if it is not already
      established. There has been no evidence for the existence of Borrelia burgdorferi
      in the province. The spirochete was not cultured from 650 Dermacentor variabilis
      ticks, nor were antibodies detected in a small sample of feral rodents using an
      indirect fluorescent antibody test. A survey of 137 dog sera samples, analyzed by
      enzyme-linked immunosorbent assay, also proved negative. There has been no
      confirmed indigenous case of Lyme disease in Nova Scotia to date.

PMID- 22416196
TI  - Comparative antifungal activity of cilofungin (LY121019) against Candida species,
      including evaluation of susceptibility testing method.
AB  - The in vitro activity of cilofungin against 100 Candida species was compared with
      5-flucytosine. amphotericin B and ketoconazole by two laboratories independently
      and in a blinded fashion using a macrotitre dilution broth method in saam-f
      medium. Cilofungin showed good in vitro activity against Candida albicans.
      Candida tropicalis and Candida glabrata (90% minimal inhibitory concentration
      [MIC] 3.2 MUg/mL) but was inactive against other Candida species. When testing
      the susceptibility of cilofungin, 5-flucytosine and amphotericin B at the two
      centres, approximately 90% of the Candida strains had MICs differing by fourfold
      or less. However, when testing susceptibility of ketoconazole, only 51% of the
      Candida strains had MIC differences fourfold or less. MIC susceptibility testing
      with cilofungin, 5-flucytosine and amphotericin B in saam-f medium is
      reproducible.

PMID- 22416197
TI  - Reduction in clinical response to empiric antimicrobial therapy of febrile
      granulocytopenic patients receiving TMP/SMX infection prophylaxis.
AB  - In the course of a multicentre clinical trial evaluating two antibacterial
      regimens for the empiric treatment of suspected infection in febrile neutropenic
      cancer patients, a suboptimal response was noted among recipients of
      antibacterial prophylaxis with trimethoprim/sulphamethoxazole (TMP/SMX).
      Multivariate analysis identified TMP/SMX prophylaxis as a predictor of poor
      outcome independent of other variables such as classification of infection,
      marrow recovery, neutrophil count at first fever, indwelling central venous
      catheter use, and underlying disease. This effect appeared to be restricted to
      recipients of tobramycin plus ticarcillin (TT). TMP/SMX suppresses potentially
      pathogenic aerobic Gram-negative bacilli and allows colonization and subsequent
      infection by Gram-positive microorganisms against which TT-like regimens have
      limited activity. Recognition of this phenomenon may permit a more appropriate
      selection of antibacterial agents for the therapy of suspected infection in the
      neutropenic patient.

PMID- 22416198
TI  - Differences between infected and noninfected patients with acute alcoholic
      hepatitis.
AB  - The medical records of 97 patients with alcoholic hepatitis, including 20 with
      coexisting bacterial infections and 77 with no evidence of bacterial infection,
      were reviewed to determine whether commonly employed tests would be useful in
      distinguishing between the two groups. The results of the study revealed that
      patients with alcoholic hepatitis and bacterial infections had higher
      temperatures (38.4+/-0.9 degrees C versus 37.9+/-0.7 degrees C, P<0.05) and white
      blood cell counts (16.4+/-7.9 versus 11.2+/-6.4*10(9)/L, P<0.005), but lower
      serum bilirubin levels (39+/-42 versus 115+/-152, P<0.05), than patients with
      alcoholic hepatitis alone. Patients with alcoholic hepatitis and bacterial
      infections also tended to reach maximum temperatures and white blood cell counts
      later in their hospital stay than patients with alcoholic hepatitis alone (5.1+/
      5.3 versus 2.5+/-1.8 days, and 7.7+/-11.8 versus 4.4+/-5.7 days, respectively,
      P<0.05 and P<0.005). These results suggest that the extent and timing of peak
      abnormalities in body temperature, white blood cell count and serum bilirubin
      level may be of value in distinguishing patients with alcoholic hepatitis with
      bacterial infections from patients with alcoholic hepatitis alone.

PMID- 22416199
TI  - Group C streptococcal endocarditis presenting as clinical meningitis: Report of a
      case and review of the literature.
AB  - Lancefield group C streptococci are known to be pathogenic in a number of animal
      species, but cause human disease much less commonly than do streptococci of
      scrogroups A or B. Reported cases of bacteremic infection, pneumonia or
      meningitis in humans have been very severe with a grave prognosis. The authors
      describe a patient who presented with classic clinical and laboratory evidence of
      bacterial meningitis which proved to be a complication of endocarditis caused by
      a group C streptococcus. This is the first reported case in which meningitis was
      the presenting manifestation of group C streptococcal endocarditis and is only
      the second case in which group C streptococcal meningitis and endocarditis have
      been associated in the same patient. A total of 13 cases of group C streptococcal
      meningitis have now been reported in the medical literature. Five of these
      patients died, and four others recovered only to be left with neurological
      sequelae. The current case confirms the seriousness of group C streptococcal
      infections in humans. Such infections are associated with a poor prognosis
      despite apparently adequate antimicrobial therapy.

PMID- 22416200
TI  - Nosocomial Legionnaires' disease: Clinical and radiographic patterns.
AB  - From 1981 to 1991, 55 patients (33 males, 22 females, mean age 58.6 years) with
      nosocomial Legionnaires' disease were studied. The mortality rate was 64%. One
      half of the patients developed nosocomial Legionnaires' disease within three
      weeks of admission. A surprising clinical feature was the low rate of findings of
      consolidation on physical examination, despite the fact that 52% of patients had
      this finding on chest radiograph. More than one-half of patients had pre-existing
      lung disease, rendering a radiographic diagnosis of pneumonia due to Legionella
      pneumophila impossible in 16% of cases despite microbiological confirmation.
      Nineteen per cent of patients who had blood cultures done had a pathogen other
      than L pneumophila isolated, suggesting dual infection in at least some of the
      patients. When the clinical and radiographic findings were combined it was noted
      that 40% of patients had one of three patterns suggestive of nosocomial
      Legionnaires' disease: rapidly progressive pneumonia, lobar opacity and multiple
      peripheral opacities. However, in 60% of patients there were no distinctive
      features.

PMID- 22416201
TI  - Bacterial biofilms and catheters: A key to understanding bacterial strategies in
      catheter-associated urinary tract infection.
AB  - Despite major technological improvements in catheter drainage systems, the
      indwelling Foley catheter remains the most common cause of nosocomial infection
      in medical practice. By approaching this common complicated urinary tract
      infection from the perspective of the biofilm strategy bacteria appear to use to
      overcome obstacles to produce bacteriuria, one appreciates a new understanding of
      these infections. An adherent biofilm of bacteria in their secretory products
      ascends the luminal and external surface of the catheter and drainage system from
      a contaminated drainage spigot or urethral meatus into the bladder. If the
      intraluminal route of bacterial ascent is delayed by strict sterile closed
      drainage or addition of internal modifications to the system, the extraluminal or
      urethral route assumes greater importance in the development of bacteriuria, but
      takes significantly longer. Bacterial growth within these thick coherent biofilms
      confers a large measure of relative resistance to antibiotics even though the
      individual bacterium remains sensitive, thus accounting for the failure of
      antibiotic therapy. With disruption of the protective mucous layer of the bladder
      by mechanical irritation, the bacteria colonizing the catheter can adhere to the
      bladder's mucosal surface and cause infection. An appreciation of the role of
      bacterial biofilms in these infections should suggest future directions for
      research that may ultimately reduce the risk of catheter-associated infection.

PMID- 22416202
TI  - Dissemination of timely national public health information.

PMID- 22416203
TI  - The serum vancomycin assay: A test of historic interest.

PMID- 22416204
TI  - Clarithromycin for children.

PMID- 22416205
TI  - Antimicrobial resistance: Journey without end.

PMID- 22416206
TI  - Nosocomial infection program.

PMID- 22416207
TI  - Comparative activity of several antimicrobial agents against nosocomial Gram
      negative rods isolated across Canada.
AB  - In 1992, a surveillance study was performed in Canada to determine the
      susceptibility of nosocomial Gram-negative rods to several wide spectrum
      antimicrobials. Consecutive isolates from 10 institutions, as well as additional
      strains of selected species of Enterobacteriaceae that are known to possess the
      Bush group 1 beta-lactamase, were tested for susceptibility to 12 antimicrobials.
      Third-generation cephalosporin resistance was found to be as high as 29% in
      Enterobacter cloacae that possesses the Bush group 1 beta-lactamase and less than
      4% in those isolates not possessing this enzyme. Cefepime equalled or exceeded
      the activity of the third-generation cephalosporins against the species of
      Enterobacteriaceae that demonstrated resistance to the third-generation
      cephalosporins.

PMID- 22416208
TI  - Activity of vancomycin, teicoplanin and cephalosporins against penicillin
      susceptible and penicillin-intermediate Streptococcus pneumoniae.
AB  - OBJECTIVE: To report in vitro susceptibilities of penicillin-susceptible and
      penicillin-intermediate Streptococcus pneumoniae isolates to cephalosporins,
      vancomycin and teicoplanin. DESIGN: Minimal inhibitory concentrations (mic) were
      determined according to National Committee for Clinical Laboratory Standards
      guidelines for 17 penicillin-susceptible isolates (mic 0.06 mg/L or less) and 16
      isolates showing intermediate susceptibility to penicillin (mic 0.12 to 1.0
      mg/L). SETTING: Tertiary care university centre. MAIN RESULTS: Comparison of the
      mic(90) values with those of other antibiotics tested demonstrated that
      ceftriaxone, cefotaxime and teicoplanin were the most active agents against
      penicillin-susceptible strains. However, teicoplanin had the lowest mic and was
      superior to other agents against strains with intermediate penicillin
      susceptibility. The mics of all cephalosporins increased in concordance with the
      mic of penicillin. CONCLUSION: Isolates demonstrating intermediate susceptibility
      or resistance to penicillin should be routinely evaluated for susceptibility to
      clinically important cephalosporins.

PMID- 22416209
TI  - Intra- and interlaboratory reproducibility of an ELISA serological test for Lyme
      disease.
AB  - OBJECTIVES: Lyme disease has been increasingly diagnosed throughout North America
      since the late 1970s. The clinical diagnosis and epidemiological monitoring of
      Lyme disease are aided by serological testing for the etiological agent, Borrelia
      burgdorferi. Numerous authorities have questioned the reproducibility of these
      serological tests. This study assessed the intra- and interlaboratory
      reproducibility of an elisa used to aid in the diagnosis of Lyme disease.
      METHODS: Twenty-seven sera from cases and noncases were tested by three
      laboratories. Two of the laboratories repeated the tests once. These testings
      were part of the 1991 quality control assessment of provincial laboratories
      carried out by the Laboratory Centre for Disease Control (lcdc), Ottawa. RESULTS:
      The mean weighted kappa statistics were 0.87 for interlaboratory comparisons and
      0.89 for intralaboratory comparisons. CONCLUSIONS: Overall, the elisa assessed in
      this study demonstrated good to excellent intra- and interlaboratory
      reproducibility in the lcdc 1991 quality control assessment when the data were
      assessed in the categorical scale using the weighted kappa statistic.
      Generalization of these findings to clinical laboratory settings must be done
      with caution.

PMID- 22416210
TI  - Eradication of methicillin-resistant Staphylococcus aureus from the lower
      respiratory tract of patients with cystic fibrosis.
AB  - Two of 95 patients followed in an adult cystic fibrosis clinic consistently grew
      methicillin-resistant Staphylococcus aureus (mrsa) on sputum culture. Sputum Gram
      stain consistently showed +4 polymorphonuclear leukocytes and +4 Gram-positive
      cocci in clusters. Both patients were co-infected with Pseudomonas aeruginosa and
      required multiple hospitalizations for treatment of pulmonary exacerbation,
      resulting in significant infection control concerns. Multiple courses of
      antibiotics, including ciprofloxacin and clindamycin regimens, failed to
      eliminate the mrsa. A combination of oral rifampin and clindamycin was successful
      in eradicating the organism from both patients. Over a 12-month period following
      therapy, in both patients none of 13 sputums showed Gram-positive cocci in
      clusters on Gram stain and none of 13 sputum cultures grew mrsa. Successful
      eradication of mrsa has greatly simplified infection control measures on
      subsequent hospitalizations, reducing costs and enhancing patient comfort.

PMID- 22416211
TI  - Escherichia coli O157:H7, other verotoxin-producing E coli and the hemolytic
      uremic syndrome in childhood.

PMID- 22416212
TI  - Mendel, fraud and the repeated analysis of data.

PMID- 22416213
TI  - Stem cells in drug screening for neurodegenerative disease.
AB  - Because the average human life span has recently increased, the number of
      patients who are diagnosed with neurodegenerative diseases has escalated. Recent
      advances in stem cell research have given us access to unlimited numbers of multi
      potent or pluripotent cells for screening for new drugs for neurodegenerative
      diseases. Neural stem cells (NSCs) are a good model with which to screen
      effective drugs that increase neurogenesis. Recent technologies for human
      embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) can provide
      human cells that harbour specific neurodegenerative disease. This article
      discusses the use of NSCs, ESCs and iPSCs for neurodegenerative drug screening
      and toxicity evaluation. In addition, we introduce drugs or natural products that
      are recently identified to affect the stem cell fate to generate neurons or glia.

PMID- 22416214
TI  - Effect of 5-FU and MTX on the Expression of Drug-resistance Related Cancer Stem
      Cell Markers in Non-small Cell Lung Cancer Cells.
AB  - Cancer stem cells (CSCs) are often characterized by the elevated expression of
      drug-resistance related stem-cell surface markers, such as CD133 and ABCG2.
      Recently, we reported that CSCs have a high level of expression of the IL-6
      receptor (IL-6R). The purpose of this study was to investigate the effect of
      anticancer drugs on the expression of the drug resistance-related cancer stem
      cell markers, ABCG2, IL-6R, and CD133 in non-small cell lung cancer (NSCLC) cell
      lines. A549, H460, and H23 NSCLC cell lines were treated with the anticancer
      drugs 5-fluorouracil (5-FU; 25 ug/ml) and methotrexate (MTX; 50 ug/ml), and the
      expression of putative CSC markers was analyzed by fluorescent activated cell
      sorter (FACS) and the gene expression level of abcg2, il-6r and cd133 by reverse
      transcriptasepolymerase chain reaction (RT-PCR). We found that the fraction of
      ABCG2-positive(+) cells was significantly increased by treatment with both 5-FU
      and MTX in NSCLC cells, and the elevation of abcg2, il-6r and cd133 expressions
      in response to these drugs was also confirmed using RT-PCR. Also, the number of
      IL-6R(+) cells was increased by MTX in the 3 cell lines mentioned and increased
      by 5-FU in the H460 cell line. The number of CD133(+) cells was also
      significantly increased by both 5-FU and MTX treatment in all of the cell lines
      tested. These results indicate that 5-FU and MTX considerably enhance the
      expression of drug-resistance related CSC markers in NSCLC cell lines. Thus, we
      suggest that antimetabolite cancer drugs, such as 5-FU and MTX, can lead to the
      propagation of CSCs through altering the expression of CSC markers.

PMID- 22416215
TI  - The characteristics of supramammillary cells projecting to the hippocampus in
      stress response in the rat.
AB  - The hypothalamus-pituitary-adrenocortex (HPA) axis is the central mediator of the
      stress response. The supramammillary (SuM) region is relatively unique among the
      hypothalamic structures in that it sends a large, direct projection to the
      hippocampal formation. It has been shown that mild stress could activate the SuM
      cells that project to the hippocampus. However, the role of these cell
      populations in modulating the stress response is not known. The present study
      examined the effect of stress on different populations of SuM cells that project
      to the hippocampus by injecting the fluorescent retrograde tracer, fluorogold
      (FG), into the hippocampus and utilizing the immunohistochemistry of choline
      acetyltransferase (ChAT), corticotrophin releasing factor (CRF), serotonin (5
      HT), glutamate decarboxylase (GAD), tyrosine hydroxylase (TH) and NADPH-d
      reactivity. Immobilization (IMO) stress (2 hr) produced an increase in the
      expression of ChAT-immunoreactivity, and tended to increase in CRF, 5-HT, GAD, TH
      immunoreactivity and nitric oxide (NO)-reactivity in the SuM cells. Fifty-three
      percent of 5-HT, 31% of ChAT and 56% of CRF cells were double stained with
      retrograde cells from the hippocampus. By contrast, a few retrogradely labeled
      cells projecting to the hippocampus were immunoreactive for dopamine, gamma
      aminobutyric acid (GABA) and NO. These results suggest that the SuM region
      contains distinct cell populations that differentially respond to stress. In
      addition, the findings suggest that serotonergic, cholinergic and corticotropin
      releasing cells projecting to the hippocampus within the SuM nucleus may play an
      important role in modulating stress-related behaviors.

PMID- 22416216
TI  - Bile Acid Inhibition of N-type Calcium Channel Currents from Sympathetic Ganglion
      Neurons.
AB  - Under some pathological conditions as bile flow obstruction or liver diseases
      with the enterohepatic circulation being disrupted, regurgitation of bile acids
      into the systemic circulation occurs and the plasma level of bile acids
      increases. Bile acids in circulation may affect the nervous system. We examined
      this possibility by studying the effects of bile acids on gating of neuronal (N)
      type Ca(2+) channel that is essential for neurotransmitter release at synapses of
      the peripheral and central nervous system. N-type Ca(2+) channel currents were
      recorded from bullfrog sympathetic neuron under a cell-attached mode using 100 mM
      Ba(2+) as a charge carrier. Cholic acid (CA, 10(-6) M) that is relatively
      hydrophilic thus less cytotoxic was included in the pipette solution. CA
      suppressed the open probability of N-type Ca(2+) channel, which appeared to be
      due to an increase in null (no activity) sweeps. For example, the proportion of
      null sweep in the presence of CA was ~40% at +40 mV as compared with ~8% in the
      control recorded without CA. Other single channel properties including slope
      conductance, single channel current amplitude, open and shut times were not
      significantly affected by CA being present. The results suggest that CA could
      modulate N-type Ca(2+) channel gating at a concentration as low as 10(-6) M. Bile
      acids have been shown to activate nonselective cation conductance and depolarize
      the cell membrane. Under pathological conditions with increased circulating bile
      acids, CA suppression of N-type Ca(2+) channel function may be beneficial against
      overexcitation of the synapses.

PMID- 22416217
TI  - Effects of Inositol 1,4,5-triphosphate on Osteoclast Differentiation in RANKL
      induced Osteoclastogenesis.
AB  - The receptor activator of NF-kappaB ligand (RANKL) signal is an activator of
      tumor necrosis factor receptor-associated factor 6 (TRAF6), which leads to the
      activation of NF-kappaB and other signal transduction pathways essential for
      osteoclastogenesis, such as Ca(2+) signaling. However, the intracellular levels
      of inositol 1,4,5-trisphosphate (IP(3)) and IP(3)-mediated cellular function of
      RANKL during osteoclastogenesis are not known. In the present study, we
      determined the levels of IP(3) and evaluated IP(3)-mediated osteoclast
      differentiation and osteoclast activity by RANKL treatment of mouse leukemic
      macrophage cells (RAW 264.7) and mouse bone marrow-derived monocyte/macrophage
      precursor cells (BMMs). During osteoclastogenesis, the expression levels of
      Ca(2+) signaling proteins such as IP(3) receptors (IP(3)Rs), plasma membrane
      Ca(2+) ATPase, and sarco/endoplasmic reticulum Ca(2+) ATPase type2 did not change
      by RANKL treatment for up to 6 days in both cell types. At 24 h after RANKL
      treatment, a higher steady-state level of IP(3) was observed in RAW264.7 cells
      transfected with green fluorescent protein (GFP)-tagged pleckstrin homology (PH)
      domains of phospholipase C (PLC) delta, a probe specifically detecting
      intracellular IP(3) levels. In BMMs, the inhibition of PLC with U73122 [a
      specific inhibitor of phospholipase C (PLC)] and of IP(3)Rs with 2
      aminoethoxydiphenyl borate (2APB; a non-specific inhibitor of IP(3)Rs) inhibited
      the generation of RANKL-induced multinucleated cells and decreased the bone
      resorption rate in dentin slice, respectively. These results suggest that
      intracellular IP(3) levels and the IP(3)-mediated signaling pathway play an
      important role in RANKL-induced osteoclastogenesis.

PMID- 22416218
TI  - A novel pathway underlying the inhibitory effects of melatonin on isolated rat
      urinary bladder contraction.
AB  - The aim of the present study was to elucidate the direct effects of melatonin on
      bladder activity and to determine the mechanisms responsible for the detrusor
      activity of melatonin in the isolated rat bladder. We evaluated the effects of
      melatonin on the contractions induced by phenylephrine (PE), acetylcholine (ACh),
      bethanechol (BCh), KCl, and electrical field stimulation (EFS) in 20 detrusor
      smooth muscle samples from Sprague-Dawley rats. To determine the mechanisms
      underlying the inhibitory responses to melatonin, melatonin-pretreated muscle
      strips were exposed to a calcium channel antagonist (verapamil), three potassium
      channel blockers [tetraethyl ammonium (TEA), 4-aminopyridine (4-AP), and
      glibenclamide], a direct voltage-dependent calcium channel opener (Bay K 8644),
      and a specific calcium/calmodulin-dependent kinase II (CaMKII) inhibitor (KN-93).
      Melatonin pretreatment (10(-8)~10(-6) M) decreased the contractile responses
      induced by PE (10(-9)~10(-4) M) and Ach (10(-9)~10(-4) M) in a dose-dependent
      manner. Melatonin (10(-7) M) also blocked contraction induced by high KCl
      ([KCl](ECF); 35 mM, 70 mM, 105 mM, and 140 mM) and EFS. Melatonin (10(-7) M)
      potentiated the relaxation response of the strips by verapamil, but other
      potassium channel blockers did not change melatonin activity. Melatonin
      pretreatment significantly decreased contractile responses induced by Bay K 8644
      (10(-11)~10(-7) M). KN-93 enhanced melatonin-induced relaxation. The present
      results suggest that melatonin can inhibit bladder smooth muscle contraction
      through a voltage-dependent, calcium-antagonistic mechanism and through the
      inhibition of the calmodulin/CaMKII system.

PMID- 22416219
TI  - Ghrelin protects spinal cord motoneurons against chronic glutamate excitotoxicity
      by inhibiting microglial activation.
AB  - Glutamate excitotoxicity is emerging as a contributor to degeneration of spinal
      cord motoneurons in amyotrophic lateral sclerosis (ALS). Recently, we have
      reported that ghrelin protects motoneurons against chronic glutamate
      excitotoxicity through the activation of extracellular signal-regulated kinase
      1/2 and phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-3beta
      pathways. Previous studies suggest that activated microglia actively participate
      in the pathogenesis of ALS motoneuron degeneration. However, it is still unknown
      whether ghrelin exerts its protective effect on motoneurons via inhibition of
      microglial activation. In this study, we investigate organotypic spinal cord
      cultures (OSCCs) exposed to threohydroxyaspartate (THA), as a model of
      excitotoxic motoneuron degeneration, to determine if ghrelin prevents microglial
      activation. Exposure of OSCCs to THA for 3 weeks produced typical motoneuron
      death, and treatment of ghrelin significantly attenuated THA-induced motoneuron
      loss, as previously reported. Ghrelin prevented THA-induced microglial activation
      in the spinal cord and the expression of pro-inflammatory cytokines tumor
      necrosis factor-alpha and interleukin-1beta. Our data indicate that ghrelin may
      act as a survival factor for motoneurons by functioning as a microglia
      deactivating factor and suggest that ghrelin may have therapeutic potential for
      the treatment of ALS and other neurodegenerative disorders where inflammatory
      responses play a critical role.

PMID- 22416220
TI  - Acute Toxicity and General Pharmacological Action of QGC EXT.
AB  - It has been shown that QGC isolated and purified from Rumecis folium found
      protective effects of gastritis and esophagitis which EXT is an ethanol extract
      of it. We examined acute toxicity and the general pharmacological action of QGC
      EXT to search for any side effects of it in rats, mice, guinea pigs, and cats. In
      a single dose toxicity study, QGC EXT didn't show toxicological effects in rats
      and mice, and the LD(50) was over 5 g/kg in both animals, and there were also no
      changes in weight, feed and water intake during these toxicological experimental
      periods. We examined the general pharmacological action on central controlled
      behavior responses, and peripheral organs including blood pressure, heart rate,
      respiration and gastrointestinal system, We found that there were no significant
      changes in body temperature, locomotors activity, stereotyped behaviors, sleeping
      time, and convulsion. In other studies, writhing reaction, normal body
      temperature, there did not appear to be any changes. The large intestine movement
      and electrical field stimulation-induced contraction was not changes by its EXT.
      In addition, the influences on blood pressure, heart rates, and respiration by
      QGC EXT were not found. These results indicate that QGC EXT may be very safe as a
      new drug, since its LD(50) was very high over 5 g/kg and any side effects were
      not found.

PMID- 22416221
TI  - Requirement of Pretone by Thromboxane A(2) for Hypoxic Pulmonary Vasoconstriction
      in Precision-cut Lung Slices of Rat.
AB  - Hypoxic pulmonary vasoconstriction (HPV) is physiologically important response
      for preventing mismatching between ventilation and perfusion in lungs. The HPV of
      isolated pulmonary arteries (HPV-PA) usually require a partial pretone by
      thromboxane agonist (U46619). Because the HPV of ventilated/perfused lungs (HPV
      lung) can be triggered without pretone conditioning, we suspected that a putative
      tissue factor might be responsible for the pretone of HPV. Here we investigated
      whether HPV can be also observed in precision-cut lung slices (PCLS) from rats.
      The HPV in PCLS also required partial contraction by U46619. In addition, K(+)
      channel blockers (4AP and TEA) required U46619-pretone to induce significant
      contraction of PA in PCLS. In contrast, the airways in PCLS showed reversible
      contraction in response to the K(+) channel blockers without pretone
      conditioning. Also, the airways showed no hypoxic constriction but a relaxation
      under the partial pretone by U46619. The airways in PCLS showed reliable,
      concentration-dependent contraction by metacholine (EC(50), ~210 nM). In summary,
      the HPV in PCLS is more similar to isolated PA than V/P lungs. The metacholine
      induced constriction of bronchioles suggested that the PLCS might be also useful
      for studying airway physiology in situ.

PMID- 22416222
TI  - Developmental Switch of the Serotonergic Role in the Induction of Synaptic Long
      term Potentiation in the Rat Visual Cortex.
AB  - Synaptic long-term potentiation (LTP) and long-term depression (LTD) have been
      studied as mechanisms of ocular dominance plasticity in the rat visual cortex.
      Serotonin (5-hydroxytryptamine, 5-HT) inhibits the induction of LTP and LTD
      during the critical period of the rat visual cortex (postnatal 3~5 weeks).
      However, in adult rats, the increase in 5-HT level in the brain by the
      administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine
      reinstates ocular dominance plasticity and LTP in the visual cortex. Here, we
      investigated the effect of 5-HT on the induction of LTP in the visual cortex
      obtained from 3- to 10-week-old rats. Field potentials in layer 2/3, evoked by
      the stimulation of underlying layer 4, was potentiated by theta-burst stimulation
      (TBS) in 3- and 5-week-old rats, then declined to the baseline level with aging
      to 10 weeks. Whereas 5-HT inhibited the induction of LTP in 5-week-old rats, it
      reinstated the induction of N-methyl-D-aspartate receptor (NMDA)-dependent LTP in
      8- and 10-week-old rats. Moreover, the selective SSRI citalopram reinstated LTP.
      The potentiating effect of 5-HT at 8 weeks of age was mediated by the activation
      of 5-HT(2) receptors, but not by the activation of either 5-HT(1A) or 5-HT(3)
      receptors. These results suggested that the effect of 5-HT on the induction of
      LTP switches from inhibitory in young rats to facilitatory in adult rats.

PMID- 22416223
TI  - Defective mitochondrial function and motility due to mitofusin 1 overexpression
      in insulin secreting cells.
AB  - Mitochondrial dynamics and distribution is critical for their role in
      bioenergetics and cell survival. We investigated the consequence of altered
      fission/fusion on mitochondrial function and motility in INS-1E rat clonal beta
      cells. Adenoviruses were used to induce doxycycline-dependent expression of wild
      type (WT-Mfn1) or a dominant negative mitofusin 1 mutant (DN-Mfn1). Mitochondrial
      morphology and motility were analyzed by monitoring mitochondrially-targeted red
      fluorescent protein. Adenovirus-driven overexpression of WT-Mfn1 elicited severe
      aggregation of mitochondria, preventing them from reaching peripheral near plasma
      membrane areas of the cell. Overexpression of DN-Mfn1 resulted in fragmented
      mitochondria with widespread cytosolic distribution. WT-Mfn1 overexpression
      impaired mitochondrial function as glucose- and oligomycin-induced mitochondrial
      hyperpolarization were markedly reduced. Viability of the INS-1E cells, however,
      was not affected. Mitochondrial motility was significantly reduced in WT-Mfn1
      overexpressing cells. Conversely, fragmented mitochondria in DN-Mfn1
      overexpressing cells showed more vigorous movement than mitochondria in control
      cells. Movement of these mitochondria was also less microtubule-dependent. These
      results suggest that Mfn1-induced hyperfusion leads to mitochondrial dysfunction
      and hypomotility, which may explain impaired metabolism-secretion coupling in
      insulin-releasing cells overexpressing Mfn1.

PMID- 22416224
TI  - System-level insights into yeast metabolism by thermodynamic analysis of
      elementary flux modes.
AB  - One of the most obvious phenotypes of a cell is its metabolic activity, which is
      defined by the fluxes in the metabolic network. Although experimental methods to
      determine intracellular fluxes are well established, only a limited number of
      fluxes can be resolved. Especially in eukaryotes such as yeast,
      compartmentalization and the existence of many parallel routes render exact flux
      analysis impossible using current methods. To gain more insight into the
      metabolic operation of S. cerevisiae we developed a new computational approach
      where we characterize the flux solution space by determining elementary flux
      modes (EFMs) that are subsequently classified as thermodynamically feasible or
      infeasible on the basis of experimental metabolome data. This allows us to
      provably rule out the contribution of certain EFMs to the in vivo flux
      distribution. From the 71 million EFMs in a medium size metabolic network of S.
      cerevisiae, we classified 54% as thermodynamically feasible. By comparing the
      thermodynamically feasible and infeasible EFMs, we could identify reaction
      combinations that span the cytosol and mitochondrion and, as a system, cannot
      operate under the investigated glucose batch conditions. Besides conclusions on
      single reactions, we found that thermodynamic constraints prevent the import of
      redox cofactor equivalents into the mitochondrion due to limits on compartmental
      cofactor concentrations. Our novel approach of incorporating quantitative
      metabolite concentrations into the analysis of the space of all
      stoichiometrically feasible flux distributions allows generating new insights
      into the system-level operation of the intracellular fluxes without making
      assumptions on metabolic objectives of the cell.

PMID- 22416225
TI  - Structural insights into a unique Legionella pneumophila effector LidA
      recognizing both GDP and GTP bound Rab1 in their active state.
AB  - The intracellular pathogen Legionella pneumophila hijacks the endoplasmic
      reticulum (ER)-derived vesicles to create an organelle designated Legionella
      containing vacuole (LCV) required for bacterial replication. Maturation of the
      LCV involved acquisition of Rab1, which is mediated by the bacterial effector
      protein SidM/DrrA. SidM/DrrA is a bifunctional enzyme having the activity of both
      Rab1-specific GDP dissociation inhibitor (GDI) displacement factor (GDF) and
      guanine nucleotide exchange factor (GEF). LidA, another Rab1-interacting
      bacterial effector protein, was reported to promote SidM/DrrA-mediated
      recruitment of Rab1 to the LCV as well. Here we report the crystal structures of
      LidA complexes with GDP- and GTP-bound Rab1 respectively. Structural comparison
      revealed that GDP-Rab1 bound by LidA exhibits an active and nearly identical
      conformation with that of GTP-Rab1, suggesting that LidA can disrupt the switch
      function of Rab1 and render it persistently active. As with GTP, LidA maintains
      GDP-Rab1 in the active conformation through interaction with its two conserved
      switch regions. Consistent with the structural observations, biochemical assays
      showed that LidA binds to GDP- and GTP-Rab1 equally well with an affinity
      approximately 7.5 nM. We propose that the tight interaction with Rab1 allows LidA
      to facilitate SidM/DrrA-catalyzed release of Rab1 from GDIs. Taken together, our
      results support a unique mechanism by which a bacterial effector protein
      regulates Rab1 recycling.

PMID- 22416226
TI  - Identification of O-mannosylated virulence factors in Ustilago maydis.
AB  - The O-mannosyltransferase Pmt4 has emerged as crucial for fungal virulence in the
      animal pathogens Candida albicans or Cryptococcus neoformans as well as in the
      phytopathogenic fungus Ustilago maydis. Pmt4 O-mannosylates specific target
      proteins at the Endoplasmic Reticulum. Therefore a deficient O-mannosylation of
      these target proteins must be responsible for the loss of pathogenicity in pmt4
      mutants. Taking advantage of the characteristics described for Pmt4 substrates in
      Saccharomyces cerevisiae, we performed a proteome-wide bioinformatic approach to
      identify putative Pmt4 targets in the corn smut fungus U. maydis and validated
      Pmt4-mediated glycosylation of candidate proteins by electrophoretic mobility
      shift assays. We found that the signalling mucin Msb2, which regulates
      appressorium differentiation upstream of the pathogenicity-related MAP kinase
      cascade, is O-mannosylated by Pmt4. The epistatic relationship of pmt4 and msb2
      showed that both are likely to act in the same pathway. Furthermore, constitutive
      activation of the MAP kinase cascade restored appressorium development in pmt4
      mutants, suggesting that during the initial phase of infection the failure to O
      mannosylate Msb2 is responsible for the virulence defect of pmt4 mutants. On the
      other hand we demonstrate that during later stages of pathogenic development Pmt4
      affects virulence independently of Msb2, probably by modifying secreted effector
      proteins. Pit1, a protein required for fungal spreading inside the infected leaf,
      was also identified as a Pmt4 target. Thus, O-mannosylation of different target
      proteins affects various stages of pathogenic development in U. maydis.

PMID- 22416227
TI  - MicroRNAs in Neural Stem Cells and Neurogenesis.
AB  - MicroRNA (miRNA) is a type of short-length (~22 nt) non-coding RNA. Most miRNAs
      are transcribed by RNA polymerase II and processed by Drosha-DGCR8 and Dicer
      complexes in the cropping and dicing steps, respectively. miRNAs are exported by
      exportin-5 from the nucleus to the cytoplasm after cropping. Trimmed mature miRNA
      is loaded and targets mRNA at the 3' or 5' untranslated region (UTR) by
      recognition of base-pairing in the miRNA-loaded RISC, where it is involved in
      gene silencing including translational repression and/or degradation along with
      deadenylation. Recent studies have shown that miRNA participates in various
      biological functions including cell fate decision, developmental timing
      regulation, apoptosis, and tumorigenesis. Analyses of miRNA expression profiles
      have demonstrated tissue- and stage-specific miRNAs including the let-7 family,
      miR-124, and miR-9, which regulate the differentiation of embryonic stem cells
      and/or neurogenesis. This review focuses on RNA-binding protein-mediated miRNA
      biogenesis during neurogenesis. These miRNA biogenesis-relating proteins have
      also been linked to human diseases because their mutations can cause several
      nervous system disorders. Moreover, defects in core proteins involved in miRNA
      biogenesis including Drosha, DGCR8, and Dicer promote tumorigenesis. Thus, the
      study of not only mature miRNA function but also miRNA biogenesis steps is likely
      to be important.

PMID- 22416229
TI  - The developing human brain: a frontiers research topic.

PMID- 22416228
TI  - Investigating the features of the m170 in congenital prosopagnosia.
AB  - Face perception generates specific neural activity as early as 170 ms post
      stimulus onset, termed the M170 when measured with Magnetoencephalography (MEG).
      We examined the M170 in six people with congenital prosopagnosia (CP) and 11
      typical controls. Previous research indicates that there are two neural
      generators for the M170 (one within the right lateral occipital area - rLO and
      one within the right fusiform gyrus - rFG), and in the current study we explored
      whether these sources reflect the processing of different types of information.
      Individuals with CP showed face-selective M170 responses within the rLO and right
      rFG, which did not differ in magnitude to those of the controls. To examine
      possible links between neural activity and behavior we correlated the CPs' MEG
      activity generated within rLO and rFG with their face perception skills. The rLO
      M170 correlated with holistic/configural face processing, whereas the rFG-M170
      correlated with featural processing. Hence, the results of our study demonstrate
      that individuals with CP can show an M170 that is within the normal range, and
      that the M170 in the rLO and rFG are involved in different aspects of face
      processing.

PMID- 22416230
TI  - CB1 Cannabinoid Receptor Expression in the Striatum: Association with
      Corticostriatal Circuits and Developmental Regulation.
AB  - Corticostriatal circuits mediate various aspects of goal-directed behavior and
      are critically important for basal ganglia-related disorders. Activity in these
      circuits is regulated by the endocannabinoid system via stimulation of CB1
      cannabinoid receptors. CB1 receptors are highly expressed in projection neurons
      and select interneurons of the striatum, but expression levels vary considerably
      between different striatal regions (functional domains). We investigated CB1
      receptor expression within specific corticostriatal circuits by mapping CB1 mRNA
      levels in striatal sectors defined by their cortical inputs in rats. We also
      assessed changes in CB1 expression in the striatum during development. Our
      results show that CB1 expression is highest in juveniles (P25) and then
      progressively decreases toward adolescent (P40) and adult (P70) levels. At every
      age, CB1 receptors are predominantly expressed in sensorimotor striatal sectors,
      with considerably lower expression in associative and limbic sectors. Moreover,
      for most corticostriatal circuits there is an inverse relationship between
      cortical and striatal expression levels. Thus, striatal sectors with high CB1
      expression (sensorimotor sectors) tend to receive inputs from cortical areas with
      low expression, while striatal sectors with low expression (associative/limbic
      sectors) receive inputs from cortical regions with higher expression (medial
      prefrontal cortex). In so far as CB1 mRNA levels reflect receptor function, our
      findings suggest differential CB1 signaling between different developmental
      stages and between sensorimotor and associative/limbic circuits. The regional
      distribution of CB1 receptor expression in the striatum further suggests that, in
      sensorimotor sectors, CB1 receptors mostly regulate GABA inputs from local axon
      collaterals of projection neurons, whereas in associative/limbic sectors, CB1
      regulation of GABA inputs from interneurons and glutamate inputs may be more
      important.

PMID- 22416231
TI  - Do patient-reported outcomes have a role in the management of patients with
      cystic fibrosis?
AB  - BACKGROUND: Health-related quality of life (HRQoL) is a rapidly growing area of
      expertise and the most commonly used patient-reported outcome (PRO). The impact
      of cystic fibrosis (CF) on HRQoL is liable to be great, making CF patients ideal
      candidates for the application of HRQoL instruments. The aims of this study were
      to assess the affect of CF on HRQoL, to ascertain the reliability and validity of
      the United Kingdom Sickness Impact Profile (UKSIP) and the Cystic Fibrosis
      Quality of Life Questionnaire (CFQoL) in the adult CF population, and to examine
      their role in the management of patients. METHODS: Seventy participants were
      recruited from the All Wales Adult Cystic Fibrosis Centre at Llandough Hospital,
      UK. There were two stages to the study: self-report of the UKSIP and CFQoL; and
      completion of the same two questionnaires 7-10 days later. RESULTS: The areas of
      HRQoL most impaired by CF were employment and concerns regarding the future. The
      UKSIP and CFQoL showed high internal consistency (ralpha = 0.89-0.93) and test
      retest reliability (r(s) = 0.57-0.94, p < 0.005) in the CF population. Validity
      was variable with the UKSIP showing discrimination across socio-demographic
      factors, whilst the CFQoL showed increased sensitivity to clinical variables.
      Many parameters influenced patient-reported HRQoL, with the greatest correlations
      seen with the Borg score (p < 0.005). The use of a HRQoL instrument in CF annual
      reviews is recommended to provide holistic patient care. The results of this
      study underpin the value of HRQoL as a patient-reported outcome measure in the
      management of adult CF.

PMID- 22416232
TI  - Inhibition of Sirtuin 2 with Sulfobenzoic Acid Derivative AK1 is Non-Toxic and
      Potentially Neuroprotective in a Mouse Model of Frontotemporal Dementia.
AB  - Tauopathies including tau-associated Frontotemporal dementia (FTD) and
      Alzheimer's disease are characterized pathologically by the formation of tau
      containing neurofibrillary aggregates and neuronal loss, which contribute to
      cognitive decline. There are currently no effective treatments to prevent or slow
      this neural systems failure. The rTg4510 mouse model, which expresses a mutant
      form of the tau protein associated with FTD with Parkinsonism-17, undergoes
      dramatic hippocampal and cortical neuronal loss making it an ideal model to study
      treatments for FTD-related neuronal loss. Sirtuins are a family of proteins
      involved in cell survival that have the potential to modulate neuronal loss in
      neurodegenerative disorders. Here we tested the hypothesis that sirtuin 2 (SIRT2)
      inhibition would be non-toxic and prevent neurodegeneration in rTg4510 brain. In
      this study we delivered SIRT2 inhibitor AK1 directly to the hippocampus with an
      osmotic minipump and confirmed that it reached the target region both with
      histological assessment of delivery of a dye and with a pharmacodynamic marker,
      ABCA1 transcription, which was upregulated with AK1 treatment. AK1 treatment was
      found to be safe in wild-type mice and in the rTg4510 mouse model, and further,
      it provided some neuroprotection in the rTg4510 hippocampal circuitry. This study
      provides proof-of-concept for therapeutic benefits of SIRT2 inhibitors in both
      tau-associated FTD and Alzheimer's disease, and suggests that development of
      potent, brain permeable SIRT2 inhibitors is warranted.

PMID- 22416233
TI  - Modulation of the Sympatho-Vagal Balance during Sleep: Frequency Domain Study of
      Heart Rate Variability and Respiration.
AB  - Sleep is a complex state characterized by important changes in the autonomic
      modulation of the cardiovascular activity. Heart rate variability (HRV) greatly
      changes during different sleep stages, showing a predominant parasympathetic
      drive to the heart during non-rapid eye movement (NREM) sleep and an increased
      sympathetic activity during rapid eye movement (REM) sleep. Respiration undergoes
      important modifications as well, becoming deeper and more regular with deep sleep
      and shallower and more frequent during REM sleep. The aim of the present study is
      to assess both autonomic cardiac regulation and cardiopulmonary coupling
      variations during different sleep stages in healthy subjects, using spectral and
      cross-spectral analysis of the HRV and respiration signals. Polysomnographic
      sleep recordings were performed in 11 healthy women and the HRV signal and the
      respiration signal were obtained. The spectral and cross-spectral parameters of
      the HRV signal and of the respiration signal were computed at low frequency and
      at breathing frequency (high frequency, HF) during different sleep stages.
      Results attested a sympatho-vagal balance shift toward parasympathetic modulation
      during NREM sleep and toward sympathetic modulation during REM sleep. Spectral
      analysis of the HRV signal and of the respiration signal indicated a higher
      respiration regularity during deep sleep, and a higher parasympathetic drive was
      also confirmed by an increase in the coherence between the HRV and the
      respiration signal in the HF band during NREM sleep. Our findings about sleep
      stage-dependent variations in the HRV signal and in the respiratory activity are
      in line with previous evidences and confirm spectral analysis of the HRV and the
      respiration signal to be a suitable tool for investigating cardiac autonomic
      modulation and cardio-respiratory coupling during sleep.

PMID- 22416234
TI  - Antioxidants and Skeletal Muscle Performance: "Common Knowledge" vs. Experimental
      Evidence.
AB  - Antioxidants are assumed to provide numerous benefits, including better health, a
      reduced rate of aging, and improved exercise performance. Specifically,
      antioxidants are commonly "prescribed" by the media, supplement industry, and
      "fitness experts" for individuals prior to training and performance, with assumed
      benefits of improved fatigue resistance and recovery. This has provoked expansion
      of the supplement industry which responded by creation of a plethora of products
      aimed at facilitating the needs of the active individual. However, what does the
      experimental evidence say about the efficacy of antioxidants on skeletal muscle
      function? Are antioxidants actually as beneficial as the general populous
      believes? Or, could they in fact lead to deleterious effects on skeletal muscle
      function and performance? This Mini Review addresses these questions with an
      unbiased look at what we know about antioxidant effects on skeletal muscle, and
      what we still need to know before conclusions can be made.

PMID- 22416235
TI  - Self-rated mental stress and exercise training response in healthy subjects.
AB  - PURPOSE: Individual responses to aerobic training vary from almost none to a 40%
      increase in aerobic fitness in healthy subjects. We hypothesized that the
      baseline self-rated mental stress may influence to the training response.
      METHODS: The study population included 44 healthy sedentary subjects (22 women)
      and 14 controls. The laboratory controlled training period was 2 weeks, including
      five sessions a week at an intensity of 75% of the maximum heart rate for 40
      min/session. Self-rated mental stress was assessed by inquiry prior to the
      training period from 1 (low psychological resources and a lot of stressors in my
      life) to 10 (high psychological resources and no stressors in my life),
      respectively. RESULTS: Mean peak oxygen uptake [Formula: see text] increased from
      34 +/- 7 to 37 +/- 7 ml kg(-1) min(-1) in training group (p < 0.001) and did not
      change in control group (from 34 +/- 7 to 34 +/- 7 ml kg(-1) min(-1)). Among the
      training group, the self-rated stress at the baseline condition correlated with
      the change in fitness after training intervention, e.g., with the change in
      maximal power (r = 0.45, p = 0.002, W/kg) and with the change in [Formula: see
      text] (r = 0.32, p = 0.039, ml kg(-1) min(-1)). The self-rated stress at the
      baseline correlated with the change in fitness in both female and male, e.g., r =
      0.44, p = 0.039 and r = 0.43, p = 0.045 for DeltaW/kg in female and male,
      respectively. CONCLUSION: As a novel finding the baseline self-rated mental
      stress is associated with the individual training response among healthy females
      and males after highly controlled aerobic training intervention. The changes in
      fitness were very low or absent in the subjects who experience their
      psychological resources low and a lot of stressors in their life at the beginning
      of aerobic training intervention.

PMID- 22416236
TI  - Keep your eyes on development: the behavioral and neurophysiological development
      of visual mechanisms underlying form processing.
AB  - Visual form perception is essential for correct interpretation of, and
      interaction with, our environment. Form perception depends on visual acuity and
      processing of specific form characteristics, such as luminance contrast, spatial
      frequency, color, orientation, depth, and even motion information. As other
      cognitive processes, form perception matures with age. This paper aims at
      providing a concise overview of our current understanding of the typical
      development, from birth to adulthood, of form-characteristic processing, as
      measured both behaviorally and neurophysiologically. Two main conclusions can be
      drawn. First, the current literature conveys that for most reviewed
      characteristics a developmental pattern is apparent. These trajectories are
      discussed in relation to the organization of the visual system. The second
      conclusion is that significant gaps in the literature exist for several age
      ranges. To complete our understanding of the typical and, by consequence,
      atypical development of visual mechanisms underlying form processing, future
      research should uncover these missing segments.

PMID- 22416237
TI  - The effects of psychosis risk variants on brain connectivity: a review.
AB  - In light of observed changes in connectivity in schizophrenia and the highly
      heritable nature of the disease, neural connectivity may serve as an important
      intermediate phenotype for schizophrenia. However, how individual variants confer
      altered connectivity and which measure of brain connectivity is more proximal to
      the underlying genetic architecture (i.e., functional or structural) has not been
      well delineated. In this review we consider these issues and the relative
      sensitivity of imaging methodologies to schizophrenia-related changes in
      connectivity. We searched PubMed for studies considering schizophrenia risk genes
      AND functional or structural connectivity. Where data was available, summary
      statistics were used to determine an estimate of effect size (i.e., Cohen's d). A
      random-effects meta-analysis was used to consider (1) the largest effect and (2)
      all significant effects between functional and structural studies. Schizophrenia
      risk variants involved in neurotransmission, neurodevelopment and myelin function
      were found to be associated with altered neural connectivity. On average,
      schizophrenia risk genes had a large effect on functional (mean d = 0.76) and
      structural connectivity (mean d = 1.04). The examination of the largest effect
      size indicated that the outcomes of functional and structural studies were
      comparable (Q = 2.17, p > 0.05). Conversely, consideration of effect size
      estimates for all significant effects suggest that reported effect sizes in
      structural connectivity studies were more variable than in functional
      connectivity studies, and that there was a significant lack of homogeneity across
      the modalities (Q = 6.928, p = 0.008). Given the more variable profile of effect
      sizes associated with structural connectivity, these data may suggest that
      structural imaging methods are more sensitive to a wider range of effects, as
      opposed to functional studies which may only be able to determine large effects.
      These conclusions are limited by methodological considerations, and require
      further investigation involving larger samples, multiple genes, and novel
      analysis techniques for confirmation.

PMID- 22416238
TI  - Consciousness and the prefrontal parietal network: insights from attention,
      working memory, and chunking.
AB  - Consciousness has of late become a "hot topic" in neuroscience. Empirical work
      has centered on identifying potential neural correlates of consciousness (NCCs),
      with a converging view that the prefrontal parietal network (PPN) is closely
      associated with this process. Theoretical work has primarily sought to explain
      how informational properties of this cortical network could account for
      phenomenal properties of consciousness. However, both empirical and theoretical
      research has given less focus to the psychological features that may account for
      the NCCs. The PPN has also been heavily linked with cognitive processes, such as
      attention. We describe how this literature is under-appreciated in consciousness
      science, in part due to the increasingly entrenched assumption of a strong
      dissociation between attention and consciousness. We argue instead that there is
      more common ground between attention and consciousness than is usually
      emphasized: although objects can under certain circumstances be attended to in
      the absence of conscious access, attention as a content selection and boosting
      mechanism is an important and necessary aspect of consciousness. Like attention,
      working memory and executive control involve the interlinking of multiple mental
      objects and have also been closely associated with the PPN. We propose that this
      set of cognitive functions, in concert with attention, make up the core
      psychological components of consciousness. One related process, chunking,
      exploits logical or mnemonic redundancies in a dataset so that it can be recoded
      and a given task optimized. Chunking has been shown to activate PPN particularly
      robustly, even compared with other cognitively demanding tasks, such as working
      memory or mental arithmetic. It is therefore possible that chunking, as a tool to
      detect useful patterns within an integrated set of intensely processed (attended)
      information, has a central role to play in consciousness. Following on from this,
      we suggest that a key evolutionary purpose of consciousness may be to provide
      innovative solutions to complex or novel problems.

PMID- 22416239
TI  - Attentional networks and consciousness.
AB  - The term consciousness is an important one in the vernacular of the western
      literature in many fields. It is no wonder that scientists have assumed that
      consciousness will be found as a component of the human brain and that we will
      come to understand its neural basis. However, there is rather little in common
      between consciousness as the neurologist would use it to diagnose the vegetative
      state, how the feminist would use it to support raising male consciousness of the
      economic plight of women and as the philosopher would use it when defining the
      really hard question of the subjective state of awareness induced by sensory
      qualities. When faced with this kind of problem it is usual to subdivide the term
      into more manageable perhaps partly operational definitions. Three meanings that
      capture aspects of consciousness are: (1) the neurology of the state of mind
      allowing coherent orientation to time and place (2) the selection of sensory or
      memorial information for awareness and (3) the voluntary control over overt
      responses. In each of these cases the mechanisms of consciousness overlap with
      one or more of the attentional networks that have been studied with the methods
      of cognitive neuroscience. In this paper we explore the overlap and discuss how
      to exploit the growing knowledge of attentional networks to constrain ideas of
      consciousness.

PMID- 22416240
TI  - Perspectives on learning styles in motor and sport skills.
AB  - We present the perspective that while coaches and instructors commonly adapt
      learning styles to maximize training outcomes, there has been little to no
      empirical support for the efficacy of this practice. Learning styles is a
      learner's preferred mode (e.g., visual, verbal) of taking in and processing new
      information. Although it is a relevant topic for the learning of motor and sport
      skills, few studies have used an appropriate methodology to test the
      effectiveness of learning style-based instruction. We highlight the need for a
      learning style assessment tool specific to motor skills and call for a test of
      the learning style hypothesis, the claim that learners will benefit from
      instruction that is tailored to their individual learning style. To this end, we
      suggest methodological guidelines.

PMID- 22416241
TI  - Characteristics of "Tip-DCs and MDSCs" and Their Potential Role in Leishmaniasis.
AB  - Since the first description of dendritic cells (DCs) by Steinman and Cohn (1973),
      the myeloid lineage of leukocytes was investigated intensively. Nowadays it is
      obvious that myeloid cells, especially DCs, are crucial for the adaptive and
      innate immune response against intracellular pathogens such as Leishmania major
      parasites. Based on the overlapping expression of molecules that were commonly
      used to classify myeloid cells, it becomes difficult to denominate those cell
      types precisely. Of note, most of these markers used for myeloid cell
      identification are expressed on a broad range of myeloid cells, and should
      therefore be handled with care if used for subtyping of myeloid cells. In this
      mini-review we aim to discuss the relative impact of DCs that release TNF and
      nitric oxide (Tip-DCs) and myeloid cells with suppressive capacities (myeloid
      derived suppressor cells, MDSCs) in infectious diseases such as experimental
      leishmaniasis. In our point of view it cannot be excluded that the novel subsets
      that were denominated as "Tip-DCs" and "MDSCs" might not be classical "subsets"
      but rather represent myeloid cells in a transient maturation stage expressing
      different genes, in response to the surrounding environment.

PMID- 22416243
TI  - Newly emerging clones of Bordetella pertussis carrying prn2 and ptxP3 alleles
      implicated in Australian pertussis epidemic in 2008-2010.
AB  - Australia is experiencing a prolonged epidemic of pertussis that began in 2008. A
      total of 194 Bordetella pertussis isolates collected from 2008 through 2010 were
      typed by single-nucleotide polymorphism (SNP) analysis, by multilocus variable
      number tandem repeats analysis, and by fim3, prn, and ptxP sequence analyses.
      Strains with 2 closely related SNP profiles carrying prn2 and ptxP3 from the
      recently emerged SNP cluster I predominated. The data suggest increasing
      selection among the B. pertussis population in Australia in favor of strains
      carrying prn2 and ptxP3 under the pressure of acellular vaccine-induced immunity.

PMID- 22416242
TI  - An Interspecies Regulatory Network Inferred from Simultaneous RNA-seq of Candida
      albicans Invading Innate Immune Cells.
AB  - The ability to adapt to diverse micro-environmental challenges encountered within
      a host is of pivotal importance to the opportunistic fungal pathogen Candida
      albicans. We have quantified C. albicans and M. musculus gene expression dynamics
      during phagocytosis by dendritic cells in a genome-wide, time-resolved analysis
      using simultaneous RNA-seq. A robust network inference map was generated from
      this dataset using NetGenerator, predicting novel interactions between the host
      and the pathogen. We experimentally verified predicted interdependent sub
      networks comprising Hap3 in C. albicans, and Ptx3 and Mta2 in M. musculus.
      Remarkably, binding of recombinant Ptx3 to the C. albicans cell wall was found to
      regulate the expression of fungal Hap3 target genes as predicted by the network
      inference model. Pre-incubation of C. albicans with recombinant Ptx3
      significantly altered the expression of Mta2 target cytokines such as IL-2 and IL
      4 in a Hap3-dependent manner, further suggesting a role for Mta2 in host-pathogen
      interplay as predicted in the network inference model. We propose an integrated
      model for the functionality of these sub-networks during fungal invasion of
      immune cells, according to which binding of Ptx3 to the C. albicans cell wall
      induces remodeling via fungal Hap3 target genes, thereby altering the immune
      response to the pathogen. We show the applicability of network inference to
      predict interactions between host-pathogen pairs, demonstrating the usefulness of
      this systems biology approach to decipher mechanisms of microbial pathogenesis.

PMID- 22416246
TI  - Diabetic Foot & Ankle - two years later and counting ....

PMID- 22416245
TI  - Functional studies of MLC1 mutations in Chinese patients with megalencephalic
      leukoencephalopathy with subcortical cysts.
AB  - Megalencephalic leukoencephalopathy with subcortical cysts (MLC, MIM# 604004) is
      an autosomal recessive inherited disease mostly resulting from MLC1 mutations. In
      this study, we finished the functional analysis of MLC1 mutations identified
      recently in Chinese patients, including five newly described missense mutations
      (R22Q, A32V, G73E, A275T, Y278H), one known nonsense mutation (Y198X), and two
      known missense mutations (S69L, T118M). We found MLC1(wt) was localized to the
      cell periphery, whereas mutant R22Q, A32V, G73E, S69L and T118M were trapped in
      the lumen of endoplasmic reticulum (ER) when we transfected the wild-type and
      mutant MLC1 in U373MG cells. Compared to wild type, the mutant G73E, T118M, Y198X
      and A275T transcript decreased and all mutants except R22Q had lower protein
      expression in transfected U373MG cells. Therefore, we propose that all these
      eight MLC1 mutations had functional effect either on their protein/mRNA
      expression, or on their intracellular protein localization, or both.

PMID- 22416247
TI  - A bio-catalytic approach to aliphatic ketones.
AB  - Depleting oil reserves and growing environmental concerns have necessitated the
      development of sustainable processes to fuels and chemicals. Here we have
      developed a general metabolic platform in E. coli to biosynthesize carboxylic
      acids. By engineering selectivity of 2-ketoacid decarboxylases and screening for
      promiscuous aldehyde dehydrogenases, synthetic pathways were constructed to
      produce both C5 and C6 acids. In particular, the production of isovaleric acid
      reached 32 g/L (0.22 g/g glucose yield), which is 58% of the theoretical yield.
      Furthermore, we have developed solid base catalysts to efficiently ketonize the
      bio-derived carboxylic acids such as isovaleric acid and isocaproic acid into
      high volume industrial ketones: methyl isobutyl ketone (MIBK, yield 84%),
      diisobutyl ketone (DIBK, yield 66%) and methyl isoamyl ketone (MIAK, yield 81%).
      This hybrid "Bio-Catalytic conversion" approach provides a general strategy to
      manufacture aliphatic ketones, and represents an alternate route to expanding the
      repertoire of renewable chemicals.

PMID- 22416248
TI  - Orbital and intracranial effects of microgravity: findings at 3-T MR imaging.
AB  - PURPOSE: To identify intraorbital and intracranial abnormalities in astronauts
      previously exposed to microgravity by using quantitative and qualitative magnetic
      resonance (MR) techniques. MATERIALS AND METHODS: The institutional review board
      approved this HIPAA-compliant, retrospective review and waived the requirement
      for informed consent. Twenty-seven astronauts (mean age +/- standard deviation,
      48 years +/- 4.5) underwent 3-T MR imaging with use of thin-section, three
      dimensional, axial T2-weighted orbital and conventional brain sequences. Eight
      astronauts underwent repeat imaging after an additional mission in space. Optic
      nerve sheath diameter (ONSD) and optic nerve diameter (OND) were quantified in
      the retrolaminar optic nerve. OND and central optic nerve T2 hyperintensity were
      quantified at mid orbit. Qualitative analysis of the optic nerve sheath, optic
      disc, posterior globe, and pituitary gland morphology was performed and
      correlated for association with intracranial evidence of hydrocephalus, vasogenic
      edema, central venous thrombosis, and/or mass lesion. Statistical analyses
      included the paired t test, Mann-Whitney nonparametric test for group
      comparisons, Cronbach alpha coefficient for reproducibility, and Pearson
      correlation coefficient. RESULTS: All astronauts had previous exposure to
      microgravity and, thus, control data were not available for comparison. The ONSD
      and OND ranged from 4.7 to 10.8 mm (mean, 6.2 mm +/- 1.1) and from 2.4 to 4.5 mm
      (mean, 3.0 mm +/- 0.5), respectively. Posterior globe flattening was seen in
      seven of the 27 astronauts (26%), optic nerve protrusion in four (15%), and
      moderate concavity of the pituitary dome with posterior stalk deviation in three
      (11%) without additional intracranial abnormalities. Retrolaminar OND increased
      linearly relative to ONSD (r = 0.797, Pearson correlation). A central area of T2
      hyperintensity was identifiable in 26 of the 27 astronauts (96%) and increased in
      diameter in association with kinking of the optic nerve sheath. CONCLUSION:
      Exposure to microgravity can result in a spectrum of intraorbital and
      intracranial findings similar to those in idiopathic intracranial hypertension.

PMID- 22416249
TI  - Deep gray matter maturation in very preterm neonates: regional variations and
      pathology-related age-dependent changes in magnetization transfer ratio.
AB  - PURPOSE: To elucidate the relationship between gestational age, pathologic
      findings, and magnetic resonance (MR) imaging measures of tissue maturation
      myelination in deep gray matter areas in very preterm neonates imaged at birth.
      MATERIALS AND METHODS: The study was approved by the research ethics board.
      Written informed consent was given by the infants' parents. Forty-two preterm
      neonates (19 boys; median gestational age, 28.7 weeks) with normal-appearing gray
      matter structures at presentation underwent MR imaging within 2 weeks of birth
      that included T1- and T2-weighted, magnetization transfer, and T1 relaxometry
      sequences. Neonates were separated into the following groups: those with normal
      findings (n = 23), those with white matter injury (WMI) (n = 9), those with grade
      I germinal matrix hemorrhage (GMH) (n = 3), and those with grade II GMH and WMI
      (n = 7). Analysis of covariance was used to determine regional effects of age and
      pathologic findings on magnetization transfer ratio (MTR) and to assess the
      relationship between MTR and T1. RESULTS: MTR increased linearly with age (P <=
      .0265), with a similar rate of change of 0.32% per week (95% confidence interval
      [CI]: 0.16, 0.49) in the basal ganglia (BG) and thalami. A lower trend (0.11% per
      week; 95% CI: -0.05, 0.28) was seen in the pons. Higher MTRs were seen in the
      thalami and pons than in the BG (P < .05), indicating earlier maturation.
      Accordingly, higher T1 values were observed in the BG relative to the thalami (P
      < .0001). Higher MTRs in the BG were observed in the group of neonates with
      normal findings at presentation than in the group with WMI (P = .02). CONCLUSION:
      MTR measurements can be used to monitor early myelination in the developing brain
      and to help detect changes in tissue that are not shown on T1- and T2-weighted MR
      images.

PMID- 22416250
TI  - Supraacetabular fossa (pseudodefect of acetabular cartilage): frequency at MR
      arthrography and comparison of findings at MR arthrography and arthroscopy.
AB  - PURPOSE: To evaluate the frequency of the supraacetabular fossa (SAF)
      (pseudodefect of acetabular cartilage) at magnetic resonance (MR) arthrography of
      the hip and to compare the MR findings with those from arthroscopy. MATERIALS AND
      METHODS: All patients gave written permission for anonymized use of their medical
      data for scientific purposes before the imaging examination. The study was
      submitted to the institutional review board, and the need to obtain additional
      approval was waived. A medical student, a radiology fellow, and two senior
      radiologists reviewed 1002 consecutive MR arthrograms for the presence of an
      accessory bony fossa in the roof of the acetabulum, or SAF. SAF was classified
      into two types: type 1, which was filled with contrast material on MR
      arthrograms, and type 2, which was filled with cartilage. The width of the SAF
      was measured on coronal and sagittal MR images. MR arthrograms showing SAF were
      evaluated for subchondral reactions. Findings at MR arthrography were compared
      with those from arthroscopy in four hip joints with SAF type 1 and 13 with SAF
      type 2. RESULTS: Sixteen of the 1002 hip joints (1.6%; four female and 12 male
      patients; mean age, 20.1 years) had SAF type 1 (mean width, 5.2 * 4.5 mm). Eighty
      nine hip joints (8.9%; 43 female and 46 male patients; mean age, 37.8 years) had
      SAF type 2 (mean width, 5.1 * 4.7 mm). No subchondral changes were found around
      the SAF. No cartilage defect was seen at the site of the SAF at arthroscopy.
      CONCLUSION: The high frequency of SAF on MR arthrograms (10.5%), the absence of
      subchondral reaction, and the absence of cartilage defects at arthroscopy
      indicate that the SAF of the acetabulum likely represents a variant.

PMID- 22416251
TI  - Spectral CT with metal artifacts reduction software for improvement of tumor
      visibility in the vicinity of gold fiducial markers.
AB  - PURPOSE: To evaluate spectral computed tomography (CT) with metal artifacts
      reduction software (MARS) for reduction of metal artifacts associated with gold
      fiducial seeds. MATERIALS AND METHODS: Thirteen consecutive patients with 37
      fiducial seeds implanted for radiation therapy of abdominal lesions were included
      in this HIPAA-compliant, institutional review board-approved prospective study.
      Six patients were women (46%) and seven were men (54%). The mean age was 61.1
      years (median, 58 years; range, 29-78 years). Spectral imaging was used for
      arterial phase CT. Images were reconstructed with and without MARS in axial,
      coronal, and sagittal planes. Two radiologists independently reviewed
      reconstructions and selected the best image, graded the visibility of the tumor,
      and assessed the amount of artifacts in all planes. A linear-weighted kappa
      statistic and Wilcoxon signed-rank test were used to assess interobserver
      variability. Histogram analysis with the Kolmogorov-Smirnov test was used for
      objective evaluation of artifacts reduction. RESULTS: Fiducial seeds were placed
      in pancreas (n = 5), liver (n = 7), periportal lymph nodes (n = 1), and
      gallbladder bed (n = 1). MARS-reconstructed images received a better grade than
      those with standard reconstruction in 60% and 65% of patients by the first and
      second radiologist, respectively. Tumor visibility was graded higher with
      standard versus MARS reconstruction (grade, 3.7 +/- 1.0 vs 2.8 +/- 1.1; P =
      .001). Reduction of blooming was noted on MARS-reconstructed images (P = .01).
      Amount of artifacts, for both any and near field, was significantly smaller on
      sagittal and coronal MARS-reconstructed images than on standard reconstructions
      (P < .001 for all comparisons). Far-field artifacts were more prominent on axial
      MARS-reconstructed images than on standard reconstructions (P < .01). Linear
      weighted kappa statistic showed moderate to perfect agreement between
      radiologists. CT number distribution was narrower with MARS than with standard
      reconstruction in 35 of 37 patients (P < .001). CONCLUSION: Spectral CT with use
      of MARS improved tumor visibility in the vicinity of gold fiducial seeds.

PMID- 22416252
TI  - Extraskeletal Ewing's sarcoma family of tumors in adults: prognostic factors and
      clinical outcome.
AB  - OBJECTIVE: The aim of this study was to evaluate prognostic factors, survival
      rate and the efficacy of the treatment modalities used in patients with
      extraskeletal Ewing's sarcoma. METHODS: Data of patients with extraskeletal
      Ewing's sarcoma followed up at our center between 1997 and 2010 were
      retrospectively analyzed. RESULTS: The median age of 27 patients was 24 years
      (range, 16-54 years). The median follow-up was 31.8 months (range, 6-144 months).
      Tumor size was between 1.5 and 14 cm (median: 8 cm). Eighty-five percent of
      patients had localized disease at presentation and 15% had metastatic disease.
      Local therapy was surgery alone in 16% of patients, surgery combined with
      radiotherapy in 42% and radiotherapy alone in 27%. All patients were treated with
      vincristine, doxorubicin, cyclophosphamide and actinomycin-D, alternating with
      ifosfamide and etoposide every 3 weeks. In patients with localized disease at
      presentation, the 5-year event-free survival and overall survival were 59.7 and
      64.5%, respectively. At univariate analysis, patients with tumor size >= 8 cm,
      high serum lactate dehydrogenase, metastasis at presentation, poor histological
      response to chemotherapy and positive surgical margin had significantly worse
      event-free survival. The significant predictors of worse overall survival at
      univariate analysis were tumor size 8 >= cm, high lactate dehydrogenase,
      metastasis at presentation, poor histological response to chemotherapy,
      radiotherapy only as local treatment and positive surgical margin. CONCLUSIONS:
      Prognostic factors were similar to primary osseous Ewing's sarcomas. Adequate
      surgical resection, aggressive chemotherapy (vincristine, doxorubicin,
      cyclophosphamide and actinomycin-D alternating with ifosfamide and etoposide) and
      radiotherapy if indicated are the recommended therapy for patients with
      extraskeletal Ewing's sarcoma.

PMID- 22416253
TI  - A case study of human papillomavirus-associated bladder carcinoma developing
      after urethral condyloma acuminatum.
AB  - We report a 35-year-old man with bladder carcinoma developing 2 months after
      urethral condyloma acuminatum, with an 8-year history of persistent human
      papilloma virus-58 infection in the urinary tract. DNA was extracted from
      paraffin-embedded tissue specimens. Human papilloma virus-6 and -58 were detected
      in the condyloma, whereas human papilloma virus-58 was detected in the carcinoma.
      In situ hybridization analysis also demonstrated high-risk human papilloma virus
      DNA signals in the condyloma and carcinoma tissues. Immunohistochemistry showed
      that p16-INK4a and mcm-7, surrogate markers of oncogenic human papilloma virus E7
      protein, were weakly expressed in the condyloma tissue but were strongly
      expressed in the carcinoma tissues, suggesting that human papilloma virus-58 was
      present in the episomal state in the condyloma, whereas human papilloma virus-58
      DNA was integrated into the host cells and its infection may have a role in the
      development of bladder carcinoma. Human papilloma virus-58 was continuously
      detected in the urethral brushing samples 8 years after treatment for urethral
      condyloma, and human papilloma virus-58 infection was still persistent in the
      urethra.

PMID- 22416254
TI  - Role of p21-activated kinase 1 in regulating the migration and invasion of
      fibroblast-like synoviocytes from rheumatoid arthritis patients.
AB  - OBJECTIVE: To investigate the role of p21-activated kinase 1 (PAK1) in regulating
      migration, invasion and MMP expression in RA fibroblast-like synoviocytes (FLS).
      METHODS: RA FLS migration and invasion in vitro were measured by the Boyden
      chamber method. Invasion of RA FLS into cartilage was detected in the severe
      combined immunodeficiency (SCID) mouse co-implantation model of RA in vivo. PAK1
      and MT1-MMP expression were examined by western blotting. ELISA was used to
      measure the production and activity of MMPs. RESULTS: Phosphorylated PAK1 (p
      PAK1) protein expression was increased in ex vivo synovial membrane cells from RA
      patients. Stimulation with IL-1beta or TNF-alpha up-regulated p-PAK1 expression.
      Inhibition of PAK1 by transfection with dominant negative PAK1 mutant (dnPAK1)
      reduced in vitro migration and invasion of RA FLS. In the SCID mouse model, RA
      FLS invasion into cartilage was attenuated by transfection with dnPAK1 in vivo.
      PAK1 regulated IL-1beta-induced production and activity of MMP-13 and MT1-MMP.
      Inhibition of MMP-13 or MT1-MMP activity also reduced RA FLS invasion.
      Furthermore, dnPAK1 transfection inhibited c-Jun N-terminal kinase (JNK)
      activation, but did not affect the activities of extracellular signal-regulated
      kinases and p38. Inhibition of the JNK activity by chemical inhibitor
      significantly reduced the migration, invasion and production of MMP-13 and MT1
      MMP. CONCLUSION: PAK1 plays an important role in regulating the migration,
      invasion and production and activity of MMPs in RA FLS, which is mediated by the
      JNK pathway. This suggests a novel strategy targeting PAK1 to prevent joint
      destruction of RA.

PMID- 22416255
TI  - Radiation-epidemiological studies of thyroid cancer incidence in Russia after the
      Chernobyl accident (estimation of radiation risks, 1991-2008 follow-up period).
AB  - This study presents an analysis of the thyroid cancer incidence in the population
      of the most contaminated territories of Bryansk, Kaluga, Oryol and Tula oblasts
      affected by the Chernobyl accident. The follow-up period is 1991-2008, and the
      cohort size is 309 130 people. For that period 978 thyroid cancer cases were
      detected. The excess relative risk per 1 Gy (ERR/Gy) is found to be statistically
      significant for children and adolescents (0-17 y of age) at the time of the
      Chernobyl accident (ERR/Gy=3.22; 95 % confidence interval (1.56; 5.81). In boys,
      the ERR/Gy was higher than in girls -6.54 and 2.24, respectively. A statistically
      significant decrease in ERR/Gy with time since exposure, by a factor of 0.37 per
      10 y, was observed for the whole cohort and for boys separately, but not for
      girls. No radiation risks of a thyroid cancer among people of 18 y of age at
      exposure and older were found.

PMID- 22416256
TI  - Early IL-10 production is essential for syngeneic graft acceptance.
AB  - We performed a comparative study and evaluated cellular infiltrates and anti
      inflammatory cytokine production at different time-points after syngeneic or
      allogeneic skin transplantation. We observed an early IL-10 production in
      syngeneic grafts compared with allografts. This observation prompted us to
      investigate the role of IL-10 in isograft acceptance. For this, we used IL-10 KO
      and WT mice to perform syngeneic transplantation, where IL-10 was absent in the
      graft or in the recipient. The majority of syngeneic grafts derived from IL-10 KO
      donors did not engraft or was only partially accepted, whereas IL-10 KO mice
      transplanted with skin from WT donors accepted the graft. We evaluated IL-10
      producers in the transplanted skin and observed that epithelial cells were the
      major source. Taken together, our data show that production of IL-10 by donor
      cells, but not by the recipient, is determinant for graft acceptance and strongly
      suggest that production of this cytokine by keratinocytes immediately upon
      transplantation is necessary for isograft survival.

PMID- 22416257
TI  - Granzyme B- and Fas ligand-mediated cytotoxic function induced by mitogenic CD28
      stimulation of human memory CD4+ T cells.
AB  - Some human memory CD4(+) T cells have cytotoxic functions best understood in the
      context of viral infections; however, their possible role in pathologic processes
      is understudied. The novel discovery that mitogenic CD28 antibodies induced
      proliferation and expansion of Tregs offered therapeutic promise for autoimmune
      disorders. However, the failed TGN1412 trial forced reassessment of this concept.
      As memory CD4(+) T cells are known to produce toxic molecules, including granzyme
      B (GrzB) and FasL, we wondered whether mitogenic CD28 was able to induce these
      cytotoxic molecules. A commercially available mitogenic human CD28 mAb (clone
      ANC28.1) was used to determine whether mitogenic CD28 induces cytotoxic function
      from human memory CD4(+) T cells. We found that stimulation of memory CD4(+) T
      cells by ANC28.1, as well as by conventional costimulation (CD3/CD28 mAb),
      robustly induced enzymatically active GrzB, along with increased surface
      expression of FasL. These functional phenotypes were induced in association with
      increased expression of T cell activation markers CD69 and CD25, and elimination
      of target cells by ANC28.1-activated memory CD4(+) T cells involved both GrzB and
      FasL. Additionally, ANC28.1-activated memory CD4(+) T cells caused disruption of
      epithelial cell monolayer integrity, which was partially mediated by GrzB. These
      findings reveal functions of memory CD4(+) T cells previously unknown to be
      induced by mitogenic CD28, and suggest that these pathogenic mechanisms may have
      been responsible for some of the widespread tissue destruction that occurred in
      the TGN1412 trial recipients.

PMID- 22416259
TI  - Pivotal Advance: Arginase-1-independent polyamine production stimulates the
      expression of IL-4-induced alternatively activated macrophage markers while
      inhibiting LPS-induced expression of inflammatory genes.
AB  - In macrophages, basal polyamine (putrescine, spermidine, and spermine) levels are
      relatively low but are increased upon IL-4 stimulation. This Th2 cytokine induces
      Arg1 activity, which converts arginine into ornithine, and ornithine can be
      decarboxylated by ODC to produce putrescine, which is further converted into
      spermidine and spermine. Recently, we proposed polyamines as novel agents in IL-4
      dependent E-cadherin regulation in AAMs. Here, we demonstrate for the first time
      that several, but not all, AAM markers depend on polyamines for their IL-4
      induced gene and protein expression and that polyamine dependency of genes relies
      on the macrophage type. Remarkably, Arg1-deficient macrophages display rather
      enhanced IL-4-induced polyamine production, suggesting that an Arg1-independent
      polyamine synthesis pathway may operate in macrophages. On the other side of the
      macrophage activation spectrum, LPS-induced expression of several proinflammatory
      genes was increased significantly in polyamine-depleted CAMs. Overall, we propose
      Arg1 independently produced polyamines as novel regulators of the inflammatory
      status of the macrophage. Indeed, whereas polyamines are needed for IL-4-induced
      expression of several AAM mediators, they inhibit the LPS-mediated expression of
      proinflammatory genes in CAMs.

PMID- 22416260
TI  - Differential diagnosis of vertebral compression fracture using in-phase/opposed
      phase and short TI inversion recovery imaging.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is highly useful for detecting
      diseases of the bone marrow. The sensitivity for detecting compression fracture
      is very high, but specificity is low for differential diagnosis between malignant
      and benign cases. PURPOSE: To evaluate the usefulness of in-phase/opposed-phase
      and short TI inversion recovery (STIR) magnetic resonance imaging (MRI) of bone
      marrow for differentiation between benign and malignant vertebral compression
      fractures. MATERIAL AND METHODS: A retrospective review of 66 patients with 70
      vertebral compression fractures was performed. The signal intensity ratio (SIR)
      defined as SIR (opposed/in) was calculated from in-phase/opposed-phase MR images,
      and the signal intensity ratio as SIR (STIR) was calculated from STIR MR images.
      The relationships between values of SIR (opposed/in) and SIR (STIR) and the
      differential diagnosis of malignant vs. benign fractures were considered.
      RESULTS: When SIR (opposed/in) was less than 1.0, bone marrow was benign. The
      bone marrow was malignant when both SIR (opposed/in) was greater than 1.0 and SIR
      (STIR) was less than 2.0. CONCLUSION: In cases of acute compression fracture,
      malignant bone marrow showed SIR(STIR) values less than 2.0 and SIR (in/opposed)
      greater than 1.0. In contrast, benign bone marrow showed SIR (STIR) values
      greater than 2.5. For chronic compression fracture, malignant bone marrow showed
      SIR (in/opposed) greater than 1.0. Bone marrow was benign in all cases with SIR
      (in/opposed) less than 1.0.

PMID- 22416258
TI  - IL-17 and IFN-gamma expression in lymphocytes from patients with active
      tuberculosis correlates with the severity of the disease.
AB  - Th1 lymphocytes are crucial in the immune response against Mycobacterium
      tuberculosis. Nevertheless, IFN-gamma alone is not sufficient in the complete
      eradication of the bacteria, suggesting that other cytokines might be required
      for pathogen removal. Th17 cells have been associated with M. tuberculosis
      infection, but the role of IL-17-producing cells in human TB remains to be
      understood. Therefore, we investigated the induction and regulation of IFN-gamma
      and IL-17 during the active disease. TB patients were classified as High and Low
      Responder individuals according to their T cell responses against the antigen,
      and cytokine expression upon M. tuberculosis stimulation was investigated in
      peripheral blood and pleural fluid. Afterwards, the potential correlation among
      the proportions of cytokine-producing cells and clinical parameters was analyzed.
      In TB patients, M. tuberculosis induced IFN-gamma and IL-17, but in comparison
      with BCG-vaccinated healthy donors, IFN-gamma results were reduced significantly,
      and IL-17 was markedly augmented. Moreover, the main source of IL-17 was
      represented by CD4(+)IFN-gamma(+)IL-17(+) lymphocytes, a Th1/Th17 subset
      regulated by IFN-gamma. Interestingly, the ratio of antigen-expanded CD4(+)IFN
      gamma(+)IL-17(+) lymphocytes, in peripheral blood and pleural fluid from TB
      patients, was correlated directly with clinical parameters associated with
      disease severity. Indeed, the highest proportion of CD4(+)IFN-gamma(+)IL-17(+)
      cells was detected in Low Responder TB patients, individuals displaying severe
      pulmonary lesions, and longest length of disease evolution. Taken together, the
      present findings suggest that analysis of the expansion of CD4(+)IFN-gamma(+)IL
      17(+) T lymphocytes in peripheral blood of TB patients might be used as an
      indicator of the clinical outcome in active TB.

PMID- 22416261
TI  - The value of diffusion tensor imaging in the differential diagnosis of
      subcortical ischemic vascular dementia and Alzheimer's disease in patients with
      only mild white matter alterations on T2-weighted images.
AB  - BACKGROUND: Diffusion tensor imaging (DTI) is a form of functional magnetic
      resonance imaging (MRI) that allows examination of the microstructural integrity
      of white matter in the brain. Dementia is a neurodegenerative disease, and DTI
      can provide indirect insights of the microstructural characteristics of brains in
      individuals with different forms of dementia. PURPOSE: To evaluate the value of
      DTI in the diagnosis and differential diagnosis of patients with subcortical
      ischemic vascular dementia (SIVD) and Alzheimer's disease (AD). MATERIAL AND
      METHODS: The study included 40 patients (20 AD patients and 20 SIVD patients) and
      20 normal controls (NC). After routine MRI and DTI, fractional anisotropy (FA)
      and apparent diffusion coefficient (ADC) values were measured and compared in
      regions of interest (ROI). RESULTS: Compared to NC and AD patients, SIVD patients
      had lower FA values and higher ADC values in the inferior-fronto-occipital
      fascicles (IFOF), genu of the corpus callosum (GCC), splenium of the corpus
      callosum (SCC), and superior longitudinal fasciculus (SLF). Compared to controls
      and SIVD patients, AD patients had lower FA values in the anterior frontal lobe,
      temporal lobe, hippocampus, IFOF, GCC, and CF; and higher ADC values in the
      temporal lobe and hippocampus. CONCLUSION: DTI can be used to estimate the white
      matter impairment in dementia patients. There were significant regional
      reductions of FA values and heightened ADC values in multiple regions in SIVD
      patients compared to AD patients. When compared with conventional MRI, DTI may
      provide a more objective method for the differential diagnosis of SIVD and AD
      disease patients who have only mild white matter alterations on T2-weighted
      imaging.

PMID- 22416262
TI  - An uncommon clinical presentation of acute limb ischemia: underscoring the role
      of perigenicular collaterals.
AB  - We present a case of atypical acute limb ischemia in a non-diabetic patient, with
      ankle-brachial pressure index of 0.6 and rest pain localized exclusively over the
      gastrocnemius muscle, sparing the foot. This uncommon presentation was attributed
      to an impaired perigenicular collateral network. Thrombolysis restored adequate
      perfusion only temporarily and was followed by thromboembolectomy. The ischemia
      presentation in our case underscores the importance of the adequacy of the
      perigeniculate collateral network for the perfusion of the tibial muscles and,
      especially, the gastrocnemius muscle.

PMID- 22416263
TI  - Traumatic ulnar artery aneurysm secondary to basketball dunk: a case report and
      review.
AB  - Ulnar artery aneurysms are uncommon lesions. They are often caused by traumatic
      injury to the hand. Ulnar artery aneurysms have been reported in association with
      multiple sports-related activities, but never secondary to a basketball injury.
      The following is a case presentation of an ulnar artery aneurysm likely formed
      secondary to repetitive basketball slam dunking with accompanying review of
      diagnosis and surgical treatment of ulnar artery aneurysms.

PMID- 22416264
TI  - How frequent are radiological abnormalities in patients with psychosis? A review
      of 1379 MRI scans.
AB  - BACKGROUND: The term psychosis refers to a combination of symptoms, without
      pointing to the origin of these symptoms. In a subset of psychotic patients,
      symptoms are attributable to an organic disease. It is important to identify
      these organic causes of psychosis early, as urgent treatment of the primary
      disease may be required. Some of these underlying organic disorders can be
      identified on magnetic resonance imaging (MRI) scans. Whether routine screening
      for all psychotic patients should therefore include MRI scans is still a matter
      of debate. METHODS: This study investigated the prevalence of clinically relevant
      abnormalities detected on MRI scans from psychotic patients and a matched control
      group. We could include MRI scans from 656 psychotic patients and 722 controls.
      The standard radiological reports of these scans were classified as normal, as a
      nonrelevant abnormality or as a clinically relevant brain abnormality by means of
      consensus, blind to diagnosis. RESULTS: A normal aspect of the brain was reported
      in 74.4% of the patients and in 73.4% of the controls. We found clinically
      relevant pathology in 11.1% of the patients and in 11.8% of the controls. None of
      the neuropathological findings observed in the patients was interpreted as a
      possible substrate for organic psychosis. Brain abnormalities that were
      classified as not clinically relevant were identified in 14.5% of the patients
      and in 14.8% of the controls. CONCLUSIONS: This suggests that MRI brain scans are
      not an essential part of routine screening for psychotic patients.

PMID- 22416265
TI  - Effects of social cognitive impairment on speech disorder in schizophrenia.
AB  - Disordered speech in schizophrenia impairs social functioning because it impedes
      communication with others. Treatment approaches targeting this symptom have been
      limited by an incomplete understanding of its causes. This study examined the
      process underpinnings of speech disorder, assessed in terms of communication
      failure. Contributions of impairments in 2 social cognitive abilities, emotion
      perception and theory of mind (ToM), to speech disorder were assessed in 63
      patients with schizophrenia or schizoaffective disorder and 21 nonpsychiatric
      participants, after controlling for the effects of verbal intelligence and
      impairments in basic language-related neurocognitive abilities. After removal of
      the effects of the neurocognitive variables, impairments in emotion perception
      and ToM each explained additional variance in speech disorder in the patients but
      not the controls. The neurocognitive and social cognitive variables, taken
      together, explained 51% of the variance in speech disorder in the patients.
      Schizophrenic disordered speech may be less a concomitant of "positive" psychotic
      process than of illness-related limitations in neurocognitive and social
      cognitive functioning.

PMID- 22416267
TI  - Where do sexually active female London students go to access healthcare? Evidence
      from the POPI (Prevention of Pelvic Infection) chlamydia screening trial.
AB  - BACKGROUND: Little is known about where sexually active female students access
      healthcare. OBJECTIVES: Using data from the Prevention of Pelvic Infection (POPI)
      cohort, the authors aimed to: Describe where sexually active female students aged
      <= 27 years reported accessing healthcare. Investigate the association between
      numbers of sexual partners during 12 months of follow-up and healthcare usage,
      health-related quality of life (EQ-5D) and demographic and behavioural
      characteristics. METHODS: Participants provided vaginal swabs and completed
      questionnaires on sexual health and quality of life at baseline and at a 12-month
      follow-up. The follow-up questionnaire also asked about healthcare attendances
      during the previous 12 months. Mann-Whitney tests were used to relate healthcare
      seeking behaviour and other characteristics to reported numbers of partners
      during follow-up. RESULTS: Of 1865 women included in the analysis, 79% paid at
      least one visit to their general practice during follow-up, 23% attended an
      accident and emergency/walk-in clinic, 21% a family planning clinic and 14% a
      genitourinary medicine clinic. As the number of sexual partners increased (0-1, 2
      3, 4+), women were more likely to have visited a genitourinary medicine clinic
      (10%, 16%, 30%, p<0.001) or accident and emergency/walk-in clinic (21%, 26%, 29%,
      p<0.002). Women with more sexual partners were also more likely to smoke, use
      condoms, be aged <16 years at sexual debut, have bacterial vaginosis, chlamydia
      or gonorrhoea at baseline and to have lower EQ5-D scores. CONCLUSION: This is the
      first UK study of healthcare attendance in multiethnic female students recruited
      outside healthcare settings. The high attendance in general practice may
      represent a valuable opportunity for screening for sexually transmitted
      infections.

PMID- 22416266
TI  - Analysis of the VAV3 as candidate gene for schizophrenia: evidences from voxel
      based morphometry and mutation screening.
AB  - In recently completed Japanese genome-wide association studies (GWAS) of
      schizophrenia (JPN_GWAS) one of the top association signals was detected in the
      region of VAV3, a gene that maps to the chromosome 1p13.3. In order to complement
      JPN_GWAS findings, we tested the association of rs1410403 with brain structure in
      healthy individuals and schizophrenic patients and performed exon resequencing of
      VAV3. We performed voxel-based morphometry (VBM) and mutation screening of VAV3.
      Four independent samples were used in the present study: (1) for VBM analysis, we
      used case-control sample comprising 100 patients with schizophrenia and 264
      healthy controls, (2) mutation analysis was performed on a total of 321 patients
      suffering from schizophrenia, and 2 case-control samples (3) 729 unrelated
      patients with schizophrenia and 564 healthy comparison subjects, and (4) sample
      comprising 1511 cases and 1517 healthy comparison subjects and were used for
      genetic association analysis of novel coding variants with schizophrenia. The VBM
      analysis suggests that rs1410403 might affect the volume of the left superior and
      middle temporal gyri (P=.011 and P=.013, respectively), which were reduced in
      patients with schizophrenia compared with healthy subjects. Moreover, 4 rare
      novel missense variants were detected. The mutations were followed-up in large
      independent sample, and one of the novel variants (Glu741Gly) was associated with
      schizophrenia (P=.02). These findings demonstrate that VAV3 can be seen as novel
      candidate gene for schizophrenia in which both rare and common variants may be
      related to increased genetic risk for schizophrenia in Japanese population.

PMID- 22416268
TI  - Analytical investigation of salivary calculi, by mid-infrared spectroscopy.
AB  - Sialolithiasis is common in salivary glands, especially in the submandibular and
      parotid ducts. X-Ray diffractometry was the principal technique used for their
      analysis, sometimes associated with scanning electron microscopy. Hydroxyapatite
      was the most frequently described constituent, in association with whitlockite
      and other calcium phosphates as brushite or octocalcium phosphate. Proteic matter
      was detected, as mucoproteins, albumin, nucleoproteins or as degenerative
      bacterial matter. This study presents the identification of constituents by mid
      infrared spectrometry of 74 sialoliths. Their successive layers are analyzed from
      their crust to the nucleus, using absorbance measurements. Spectra are compared
      with reference mixtures of two or more constituents. Approximately 99% of
      sialoliths are constituted of calcium phosphates, under carbonated forms. More
      than three-quarters contain proteins, in which mucins represent the majority and
      albumin is found in 10% of all the specimens. Only 7% calculi are an association
      of two constituents, 66% are made of three and 27% have four or more components.
      For the 74 studied sialoliths, no specimen contains hydroxyapatite; but they are
      composed of carbonate apatites with irregular microcrystallized forms, even if
      proteins are present. Some of them have a pure protein nucleus, surrounded by
      carbonate apatite layers; the other stones are made of internal layers of
      apatites and covered with a dense and varnished crust of proteins.

PMID- 22416269
TI  - A promising dehydrogenase-based bioanode for a glucose biosensor and glucose/O2
      biofuel cell.
AB  - A new type of dehydrogenase-based amperometric glucose biosensor was constructed
      using glucose dehydrogenase (GDH) which was immobilized on the edge-plane
      pyrolytic graphite (EPPG) electrode modified with poly(phenosafranin)
      functionalized single-walled carbon nanotubes (PPS-SWCNTs). The PPS-SWCNT
      modified EPPG electrode was prepared by electropolymerization of phenosafranin on
      the EPPG electrode which had been previously coated with SWCNTs. The performance
      of the GDH/PPS-SWCNT/EPPG bioanode was evaluated using cyclic voltammetry and
      amperometry in the presence of glucose. The GDH/PPS-SWCNT/EPPG electrode
      possesses promising characteristics as a glucose sensor: a wide linear dynamic
      range of 50 to 700 MUM, low detection limit of 0.3 MUM, fast response time (1-2
      s), high sensitivity (96.5 MUA cm(-2) mM(-1)), and anti-interference and anti
      fouling abilities. Moreover, the performance of the GDH/PPS-SWCNT/EPPG bioanode
      was tested in a glucose/O(2) biofuel cell. The maximum power density delivered by
      the assembled glucose/O(2) biofuel cell could reach 64.0 MUW cm(-2) at a cell
      voltage of 0.3 V with 40 mM glucose.

PMID- 22416270
TI  - Wireless fast-scan cyclic voltammetry measurement of histamine using WINCS--a
      proof-of-principle study.
AB  - Histamine is among the most poorly understood biogenic amines, yet the
      histaminergic system spreads throughout the brain and has been implicated in
      functions as diverse as homeostasis and synaptic plasticity. Not surprisingly
      then, it has been linked to a number of conditions including minimally conscious
      state, persistent vegetative state, epilepsy, addiction, cluster headache,
      essential tremor, and Parkinson's disease. We have previously reported that the
      Wireless Instantaneous Neurotransmitter Concentration Sensing (WINCS) system can
      monitor dopamine, serotonin, and adenosine using fast-scan cyclic voltammetry
      (FSCV). Here, we demonstrate the expanded capability of the WINCS system to
      measure histamine. The optimal FSCV waveform was determined to be a triangle wave
      scanned between -0.4 and +1.4 V at a rate of 400 V s(-1) applied at 10 Hz. Using
      this optimized FSCV parameter, we found histamine release was induced by high
      frequency electrical stimulation at the tuberomammillary nucleus in rat brain
      slices. Our results suggest that the WINCS system can provide reliable, high
      fidelity measurements of histamine, consistently showing oxidative currents at
      +1.3 V, a finding that may have important clinical implications.

PMID- 22416271
TI  - Integration of gas chromatography mass spectrometry methods for differentiating
      ricin preparation methods.
AB  - The investigation of crimes involving chemical or biological agents is
      infrequent, but presents unique analytical challenges. The protein toxin ricin is
      encountered more frequently than other agents and is found in the seeds of
      Ricinus communis, commonly known as the castor plant. Typically, the toxin is
      extracted from castor seeds utilizing a variety of different recipes that result
      in varying purity of the toxin. Moreover, these various purification steps can
      also leave or differentially remove a variety of exogenous and endogenous
      residual components with the toxin that may indicate the type and number of
      purification steps involved. We have applied three gas chromatography-mass
      spectrometry (GC-MS) based analytical methods to measure the variation in seed
      carbohydrates and castor oil ricinoleic acid, as well as the presence of solvents
      used for purification. These methods were applied to the same samples prepared
      using four previously identified toxin preparation methods, starting from four
      varieties of castor seeds. The individual data sets for seed carbohydrate
      profiles, ricinoleic acid, or acetone amount each provided information capable of
      differentiating different types of toxin preparations across seed types. However,
      the integration of the data sets using multivariate factor analysis provided a
      clear distinction of all samples based on the preparation method, independent of
      the seed source. In particular, the abundance of mannose, arabinose, fucose,
      ricinoleic acid, and acetone were shown to be important differentiating factors.
      These complementary tools provide a more confident determination of the method of
      toxin preparation than would be possible using a single analytical method.

PMID- 22416272
TI  - Azithromycin antimicrobial resistance and genital Chlamydia trachomatis
      infection: duration of therapy may be the key to improving efficacy.

PMID- 22416273
TI  - What is the International Union against Sexually Transmitted Infections?

PMID- 22416274
TI  - A naphthalene exciplex based Al3+ selective on-type fluorescent probe for living
      cells at the physiological pH range: experimental and computational studies.
AB  - 2-((Naphthalen-6-yl)methylthio)ethanol (HL) was prepared by one pot synthesis
      using 2-mercaptoethanol and 2-bromomethylnaphthalene. It was found to be a highly
      selective fluorescent sensor for Al(3+) in the physiological pH (pH 7.0-8.0). It
      could sense Al(3+) bound to cells through fluorescence microscopy. Metal ions
      like Mn(2+), Fe(3+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Ag(+), Cd(2+), Hg(2+),
      Cr(3+) and Pb(2+) did not interfere. No interference was also observed with
      anions like Cl(-), Br(-), F(-), SO(4)(2-), NO(3)(-), CO(3)(2-), HPO(4)(2-) and
      SCN(-). Experimentally observed structural and spectroscopic features of HL and
      its Al(3+) complex have been substantiated by computational calculations using
      density functional theory (DFT) and time dependent density functional theory
      (TDDFT).

PMID- 22416275
TI  - From sulfenylation to sulfhydration: what a thiolate needs to tolerate.
AB  - There is a growing appreciation that oxidants such as hydrogen peroxide
      (H(2)O(2)) and gases such as nitric oxide (NO) and hydrogen sulfide (H(2)S) can
      act as modulators of various signaling pathways. Much of this signaling occurs
      through the modifications of specific, critical cysteine residues in target
      proteins. How such small, diffusible molecules (H(2)O(2), NO, H(2)S) can achieve
      the required specificity is incompletely understood. Now, new findings provide
      considerable insight into these and related questions.

PMID- 22416276
TI  - Regulation of the EGF transcriptional response by endocytic sorting.
AB  - Ligand binding to the epidermal growth factor receptor (EGFR) on the cell surface
      activates the extracellular signal-regulated kinase (ERK) cascade. Activated,
      ligand-bound receptors are internalized, and this process may contribute to
      termination of signaling or enable signaling from intracellular sites. ESCRT
      (endosomal sorting complex required for transport) complexes may contribute to
      termination of signaling by sorting receptors into intraluminal vesicles of
      multivesicular endosomes from which the receptors continue into lysosomes for
      degradation. We showed that depletion of ESCRTs, which causes the retention of
      the EGFR in endosomes, increased the activation of the EGFR and its downstream
      kinases but had little effect on the overall profile and amplitude of the EGF
      induced transcriptional response. In contrast, interfering with receptor
      endocytosis or ubiquitination to keep the EGFR at the cell surface stimulated
      increases in the abundance of many EGF-induced transcripts, similar to those
      induced by EGFR overexpression. We also found that the complete EGF
      transcriptional program was rapidly activated after ligand binding to the
      receptor. We conclude that the transcriptional response is elicited primarily by
      receptor molecules at the cell surface.

PMID- 22416278
TI  - The need for customized and standardized health care quality measures.

PMID- 22416279
TI  - Faculty development in quality improvement: crossing the educational chasm.

PMID- 22416280
TI  - Progress on a national patient safety imperative to eliminate CLABSI.

PMID- 22416277
TI  - Proteome-wide discovery of evolutionary conserved sequences in disordered
      regions.
AB  - At least 30% of human proteins are thought to contain intrinsically disordered
      regions, which lack stable structural conformation. Despite lacking enzymatic
      functions and having few protein domains, disordered regions are functionally
      important for protein regulation and contain short linear motifs (short peptide
      sequences involved in protein-protein interactions), but in most disordered
      regions, the functional amino acid residues remain unknown. We searched for
      evolutionarily conserved sequences within disordered regions according to the
      hypothesis that conservation would indicate functional residues. Using a
      phylogenetic hidden Markov model (phylo-HMM), we made accurate, specific
      predictions of functional elements in disordered regions even when these elements
      are only two or three amino acids long. Among the conserved sequences that we
      identified were previously known and newly identified short linear motifs, and we
      experimentally verified key examples, including a motif that may mediate
      interaction between protein kinase Cbk1 and its substrates. We also observed that
      hub proteins, which interact with many partners in a protein interaction network,
      are highly enriched in these conserved sequences. Our analysis enabled the
      systematic identification of the functional residues in disordered regions and
      suggested that at least 5% of amino acids in disordered regions are important for
      function.

PMID- 22416281
TI  - The correct business case for the Michigan Keystone Patient Safety Program in
      ICUs.

PMID- 22416282
TI  - Disruptive change in medicine: reflections of a student.

PMID- 22416283
TI  - Salinomycin toxicity causes deaths of calves on two Scottish dairy farms.

PMID- 22416284
TI  - Thermodynamics of exciton/polaritons in one and two dimensional organic single
      crystal microcavities.
AB  - We consider here the thermodynamics and phase-diagram of exciton/polaritons
      formed in low-dimensional organic single-crystal microcavities. Using the Dicke
      model for a lattice of Frenkel excitons coupled to a common cavity mode, we
      explore the transition between normal and condensate regimes as depending upon
      the exciton band-width and temperature of the polariton gas. We show that for one
      dimensional conjugated polymers, the coexistence curve at low temperatures shifts
      towards lower critical coupling strengths as the exciton band-width is increased.
      We also consider the effect of orientational disorder in a two-dimensional
      polyacene slab on the formation of the polariton BEC. Our results indicate that
      while a small degree of orientational disorder will not have a profound effect on
      the critical exciton/photon coupling strength needed to produce the transition
      from normal to BEC regimes, BEC will likely be suppressed in glassy or strongly
      disordered molecular films.

PMID- 22416285
TI  - The diagnosis and management of ovarian hyperstimulation syndrome: No. 268,
      November 2011.
AB  - OBJECTIVE: To review the clinical aspects of ovarian hyperstimulation syndrome
      and provide recommendations on its diagnosis and clinical management. OUTCOMES:
      These guidelines will assist in the early recognition and management of ovarian
      hyperstimulation. Early recognition and prompt systematic supportive care will
      help avert poor outcomes. EVIDENCE: Medline, Embase, and the Cochrane database
      were searched for relevant articles, using the key words "ovarian
      hyperstimulation syndrome" and "gonadotropins," and guidelines created by other
      professional societies were reviewed. VALUES: The quality of evidence was rated
      using the criteria described in the Report of the Canadian Task Force on
      Preventive Health Care. Recommendations for practice were ranked according to the
      method described in that report (Table 1).

PMID- 22416287
TI  - Abstracts of the IOF-ECCEO12 European Congress on Osteoporosis and
      Osteoarthritis, March 21-24, 2012 and the 2nd IOF-ESCEO Pre-clinical Symposium,
      March 23-24, 2012, Bordeaux, France.

PMID- 22416286
TI  - Editor's introduction.

PMID- 22416288
TI  - Amacrine cells: seeing the forest and the trees.

PMID- 22416290
TI  - Abstracts of the 43rd Annual Meeting of the Society of Gynecologic Oncology.
      March 24-27, 2012. Austin, Texas, USA.

PMID- 22416289
TI  - The tasks of amacrine cells.
AB  - Their unique patterns of size, numbers, and stratification indicate that amacrine
      cells have diverse functions. These are mostly unknown, as studies using imaging
      and electrophysiological methods have only recently begun. However, some of the
      events that occur within the amacrine cell population--and some important
      unresolved puzzles--can be stated purely from structural reasoning.

PMID- 22416291
TI  - Measurement of knee joint gaps without bone resection: "physiologic" extension
      and flexion gaps in total knee arthroplasty are asymmetric and unequal and
      anterior and posterior cruciate ligament resections produce different gap
      changes.
AB  - General agreement is that flexion and extension gaps should be equal and
      symmetrical in total knee arthroplasty (TKA) procedures. However, comparisons
      using a standard TKA approach to normal knee joints that have not undergone bone
      resection are currently unavailable. Since bony preparation can influence capsule
      and ligament tension, our purpose was to perform measurements without this
      influence. Ten normal cadaveric knees were assessed using a standard medial
      parapatellar TKA approach with patellar subluxation. Gap measurements were
      carried out twice each alternating 100 and 200 N per compartment using a
      prototypical force-determining ligament balancer without the need for bony
      resection. Initial measurements were performed in extension, followed by 908 of
      flexion. The ACL was then resected, and finally the PCL was resected, and
      measurements were carried out in an analogous fashion. In general, the lateral
      compartment could be stretched further than the medial compartment, and the
      corresponding flexion gap values were significantly larger. ACL resection
      predominantly increased extension gaps, while PCL resection increased flexion
      gaps. Distraction force of 100 N per compartment appeared adequate; increasing to
      200 N did not improve the results.

PMID- 22416292
TI  - Manuscripts from the European Venous Course. Forewrod.

PMID- 22416293
TI  - Nontraditional marriage: how to write electronic reports by hand: process faster
      and easier for West Virginia providers.

PMID- 22416294
TI  - Puzzles in practice. Cement pulmonary embolism.

PMID- 22416295
TI  - [New possibilities of educating Czech surgeons in oncologic surgery].

PMID- 22416296
TI  - Mandated benefits.

PMID- 22416297
TI  - Managed care.

PMID- 22416298
TI  - Medicaid waivers.

PMID- 22416299
TI  - Medicaid copayments.

PMID- 22416300
TI  - Medicaid provider tax.

PMID- 22416301
TI  - Benefits and services.

PMID- 22416302
TI  - Medicaid eligibility.

PMID- 22416303
TI  - Federal Medicaid policy.

PMID- 22416304
TI  - Medicaid reimbursement.

PMID- 22416305
TI  - Yoga, public health, and the problem of getting noticed.

PMID- 22416306
TI  - Case X: Irish reproductive policy and European influence.

PMID- 22416307
TI  - Medicaid restructuring.

PMID- 22416308
TI  - Mindfulness, meditation and yoga: competition or collaboration?

PMID- 22416309
TI  - Democracy and women in Turkey: in defense of liberalism.

PMID- 22416310
TI  - Equality with a difference: gender and citizenship in transitional Palestine.

PMID- 22416312
TI  - [The shape of power and society in 16th-century Terraferma].

PMID- 22416313
TI  - ["Il caffe dell'unita": public and private in the Communist family during the
      1950's].

PMID- 22416314
TI  - [The history of childhood in Italy: recent    studies, obscure areas, open
      questions].

PMID- 22416315
TI  - [Servant education in the 19th century: literature for servitude].

PMID- 22416318
TI  - Environmentalism in developing countries and the case of a large Korean city.

PMID- 22416319
TI  - Green versus Brown: explaining environmental commitment in Australia.

PMID- 22416321
TI  - [Suexametonium in paediatric anesthesia - an ambiguous issue].

PMID- 22416322
TI  - Safety net in the era of health reform: a new vision of care.
AB  - The collection of services and providers that making up the safety net system
      plays a crucial role in providing health care to the nearly 50 million uninsured
      adults and children nationwide (Kaiser Commission on Medicaid and the Uninsured
      2011a). Passage of the Patient Protection and Affordable Care Act (ACA) presents
      both opportunities and significant challenges for this system. The health reform
      law will extend health insurance coverage to more than 30 million individuals by
      2014. At the same time, it will invest significantly in building provider and
      clinic capacity, as well as in more coordinated and integrated care delivery
      systems (Summer 2011). This influx of patients will place increased demands on a
      system that is already experiencing capacity, financial, and workforce stressors.
      This issue brief focuses on some of the daily challenges facing the safety net,
      as well as new challenges and opportunities that will emerge as health reform
      unfolds. Philanthropy has long supported many aspects of the safety net,
      including developing the business and clinical structure and infrastructure, such
      as health information technology and strengthening the primary care and
      paraprofessional workforce. Philanthropy has also helped increase the capacity of
      community clinics and other safety net providers and expand the services
      associated with patient-centered care models to include translation,
      transportation, health literacy support, and community prevention. This paper
      highlights some of these efforts, and outlines areas of opportunity for funder
      investment in the safety net in this era of health reform.

PMID- 22416323
TI  - Too few choices, too much junk: connecting food & health.

PMID- 22416324
TI  - Family composition and sex-differential mortality among children in early modern
      Japan.

PMID- 22416325
TI  - Visions of domesticity in the African women's homecraft movement in Rhodesia.

PMID- 22416326
TI  - Historicizing power and responses to power: indirect rule and its reform.

PMID- 22416328
TI  - Hope and despair in the writings of William Cowper.

PMID- 22416329
TI  - How the potato changed the world's history.

PMID- 22416330
TI  - Sweet Polychrest.

PMID- 22416331
TI  - It's all about power: the political economy and ecology of redefining the
      Brazilian Amazon.

PMID- 22416333
TI  - Thailand's responses to transnational migration during economic growth and
      economic downturn.

PMID- 22416336
TI  - The Singapore state's response to migration.

PMID- 22416337
TI  - Portraits of emigration: sour milk and honey in the promised land.

PMID- 22416338
TI  - The ties that bind: persistence in a New World industrial suburb, 1902-22.

PMID- 22416339
TI  - Urban society and the opportunity structure in New Zealand, 1902-22: the
      Caversham project.

PMID- 22416340
TI  - Young men and the sea: the sociology of seafaring in eighteenth-century Salem,
      Massachusetts.

PMID- 22416341
TI  - One payer's attempt to spur primary care doctors to form new medical homes.
      Interview by Susan Dentzer.

PMID- 22416342
TI  - [Future of the "Brain and Nerve": a discussion].

PMID- 22416343
TI  - [Influence of antibody-mediated immune pressure on neuraminidase gene mutations
      of avian influenza virus H9N2].
AB  - LG1 strain of avian influenza virus H9N2 was passaged continuously for 40
      generations in chicken embryos with anti-LG1 maternal antibodies in 4 parallel
      experiments, of which 3 experiments had a stable mutation of "G" to "A" at #99 of
      the neuraminidase gene(NA)from the 20th passage resulting in a change of Met to
      Ile and 2 had a stable mutation of "A" to "G" at #473 of the NA gene from the
      30th passage resulting in a change of Asn to Ser which occurred in the 50th
      passage of another experiment. Eighty continuous passages in chicken embryos
      without antibody did not have the same mutation, indicating that the mutations of
      the 2 positions were associated with selective pressure of antibodies. Analysis
      of the ratios of nonsynonium (NS) vs synonium (S) mutations of nucleic acids
      demonstrated that NS/S of 4 parallel experiments with antibodies was 4.6 (32/7)
      compared with 2.0 (16/8) of the 2 experiments without antibodies and this
      significant difference implied the selective pressure of antibodies.

PMID- 22416344
TI  - [Genome sequencing and phylogenetic analysis of avian influenza viruses subtype
      H9N2].
AB  - Samples of chicken, duck, quail, and pigeon were collected from Jiangsu, Anhui,
      and Hebei in 2009-2011, and sixteen H9N2 subtype isolates of avian influenza
      virus (AIV) were identified. The eight full-length genes of 16 AIV isolates were
      amplified by RT-PCR and sequenced. Genome sequence analysis showed that the amino
      acid motif of cleavage sites in the HA gene was P-S-R/K-S-S-R, which was
      consistent with the characterization of the LPAIV, and the Leucine (L) at the
      amino acid position 226 in the HA genes of all isolates indicated the potential
      of binding with SAalpha, 2-6 receptor. All isolates had a S to N substitution at
      residue 31 in the M2 gene, which is related to the resistance phenotype of
      adamantanes. The key molecular features of 16 AIV isolates from different hosts
      were same. Genome phylogenetic analysis revealed that all 16 H9N2 subtype AIVs
      originated from F98-like virus as backbone and formed two new genotypes through
      reassortment with HA gene of Y280-like virus and PB2 and M genes of G1-like
      virus. Our findings suggest that more attention should be paid to the
      surveillance of H9N2 influenza virus and its direction of reassortment.

PMID- 22416345
TI  - [Plutella xylostella granulovirus PP31 interacts with two host proteins].
AB  - Protein-protein interactions between viruses and hosts are common during viral
      infection and replication. In this study, a cDNA library from larvae of Plutella
      xylostella was constructed and used for screening of genes encoding proteins
      interacting with Plutella xylostella granulovirus (PlxyGV) proteins. Two cDNA
      clones containing genes encoding proteins interacting with PlxyGV PP31 were
      identified by yeast two-hybrid assays. Sequence analysis showed that the genes
      encoded homologues of receptor for activated protein C kinase (RACK) and
      methionine aminopeptidase 2 (MetAP2), respectively. The P. xylostella rack gene
      and the PlxyGV pp31 was expressed in an E. coli strain to produce proteins fused
      with a 6-His or a GST tag. It was shown that the rack was expressed as a 38kD
      peptide as prospected. The 38kD His-tagged peptide was co-purified with GST-PP31
      by GST-bind resin in GST-pulldown assays, confirming interaction between the
      PlxyGV PP31 and the RACK protein of P. xylostella.

PMID- 22416347
TI  - [Construction and transfection experiment of a goose circovirus infectious
      clone].
AB  - A pair of primers with BamH I restriction site were designed to amplify the
      complete genome of goose circovirus. Two copies of the genome were ligated in
      tandem and cloned into pGEM-T Easy vector to construct an infectious clone named
      as pGEMT-2GoCV. The pGEMT-2GoCV linearized with EcoR I was transfected to
      negative embryos and gosling with Lipfectamine. PCR detection verified the
      proliferation of GoCV in geese. Some sera of the embryo transfected group were
      detected to be positive at 2 and 4 weeks after hatching and one bursa was
      detected to be positive at 4 weeks. Some sera of the gosling transfected group
      were also detected to be positive at 2 weeks after transfection. Furthermore, the
      mark in the PCR products were identified by BamH I digestion and the GoCV in
      positive tissue and sera were quantitated by Real-time PCR. The results showed
      that the virus load in positive bursa was 1.57 x 10(6) copies/mg, the virus load
      in positive sera were 3.52 x 10(4)-5.92 x 10(5) copies/microL. In conclusion, the
      infectious DNA clone constructed with two copies of full-length GoCV genome in
      tandem can transfect embryo and gosling and propagate the marked goose
      circovirus.

PMID- 22416346
TI  - [Prokaryotic expression of HN gene of bovine parainfluenza virus type 3 and the
      establishment of indirect ELISA method].
AB  - The prokaryotic expression plasmid pQE30-HN of hemagglutinin-neuraminidase (HN)
      protein gene of bovine parainfluenza virus type 3 (BPIV3) strain HJ-1 was
      expressed by IPTG induction in E. coli XL1Blue. The recombinant HN protein(rHN)
      was purified by electroeluting method, and used as coated antigen. An indirect
      enzyme-linked immunosorbent assay (ELISA) was developed to detect the antibody
      valence of BPIV3. The best working conditions of ELISA were as follows: the
      antigen concentration was 6 microg/mL; the serum dilution was 1:50; the blocking
      reagent was 5% skimmed milk; the blocking time was 60 min at 37 degrees C; the
      second antibody concentration was 1:10 000; The cut-off value was 0.30. The
      method revealed a good specificity, no cross-reaction to the positive sera of
      BCV, IBRV or BRSV was observed. We applied the method to detect 323 serum samples
      of dairy cow in Heilongjiang Province, the seropositivity rate of BPIV3 was about
      58%. The indirect ELISA established provided a technological basis for the
      development of ELISA kit.

PMID- 22416348
TI  - [Effect of BYDV-MP nuclear localization signal on the movement of PVX].
AB  - Abstract:By using PVX derived vector pGR107, the effect of BYDV-MP nuclear
      localization signal on the movement of PVX was studied. BYDV-MP was cloned into
      pGR107 using GFP as an indicator. BYDV-MP was then shown to induce the systemic
      infection and exacerbate the symptom of PVX through infecting Nicotiana
      benthamiana. When the PVX gene encoding 25kD protein, which functioned as a
      systematic movemnet protein,was deleted and the above experiment was repeated,
      the result showed that BYDV-MP could compensate the systemic movement of PVX. A
      serial mutants with substitutions on the fifth, sixth and seventh amino acids of
      BYDV-MP nuclear localization signal was further constructed. It was found that
      the mutants at the fifth, sixth amino acids in BYDV-MP nuclear localization
      signal could only delay or weaken systemic movement of PVX whereas the mutant at
      seventh amino acid could entirely inhibit systemic movement of PVX.

PMID- 22416349
TI  - [Study on the effect of realgar nanoparticles on reducing the respiratory
      syncytial virus type A (RSV-a) replication in vitro].
AB  - This study was to establish a model to explore anti- RSV effect of different
      administration method of Chinese medicine realgar on respiratory syncytial virus
      type A (RSV-A) replication in Hep-2 cells. Using high-energy ball milling with
      distilled water to prepare realgar nanoparticles,the concentration of nanometer
      realgar was tested by molybdenum blue staining method and the size of realgar
      nanoparticles was tested on Nano Series. Cell culture with ribavirin as a
      positive control was applied to observe the effect of anti-respiratory syncytial
      virus type A replication through prevention, treatment or direct inactivation of
      three different drug administration methods. Realgar nano-particles was found to
      be a potential inhibitor of RSV-A in a concentration-dependent manner with the
      median toxic concentration(TC50) of 0.649 microg/mL in Hep-2 cell culture. The
      median inhibition concentration (IC50) was 0.20 microg/mL when drug was added
      before virus infection. The IC50 was 0.13 microg/mL when drug was added after
      virus infection,and it was 0.16 microg/mL when the drug was mixed with virus and
      added. The therapeutic index (TI) was 3.18, 4.99 and 4.11, respectively. The
      results showed realgar nanoparticles could inhibit the replication of the RSV and
      inactivate the RSV in vitro.

PMID- 22416350
TI  - [Prokaryotic expression and identification of HPV16 E7 protein].
AB  - HPV16 E7 fusion protein was expressed in E. coli BL21, and its applied value for
      HPV was evaluated. HPV16 E7 gene was amplified by PCR, and cloned into
      prokaryotic expression vector pGEX6p-1. The recombinant plasmid was transformed
      into E. coli BL21, and HPV16 E7 fusion was expressed through IPTG induction. The
      expressed product was analyzed by SDS-PAGE and Western blot, subsequently
      purified according to Glutathione Sepharose 4B purification procedure. An
      indirect ELISA with the purified fusion protein as the coating antigen was then
      established to detect E7 serum antibodies from mice immunized with recombinant
      Listeria monocytogenes delivering HPV16 E7. The results demonstrated that the
      soluble fusion protein was highly expressed at 25 degrees C after induction with
      0.5 mM IPTG. Furthermore, the result of Western blot analysis showed that the
      fusion protein had good specific reaction with an anti-E7 monoclonal antibody.
      Indirect ELISA result confirmed that the fusion protein could detect the serum
      antibodies against E7 with a titer of 1:200. The expressed GST-E7 fusion protein
      was immunocompetent, which was useful in the research of E7 biological function
      and therapeutic vaccine.

PMID- 22416351
TI  - [Development of a GeXP based multiplex RT-PCR assay for simultaneous detection of
      eight arboviruses related to encephalitis].
AB  - Multiplex reverse transcription-polymerase chain reaction (mRT-PCR) is currently
      available in virus detection and defined as the simultaneous amplification of two
      or more DNA/RNA targets in a single reaction vessel. In this study, we attempted
      to modify the conventional mRT-PCR technique on a basis of GenomeLab Genetic
      Analysis System (GeXP). Initially, we optimized the analytical validation of the
      GeXP analyzer and its design of workflow and simultaneously detected eight
      arboviruses that related to epidemic encephalitis by verifying the specificity of
      mRT-PCR with Japanese encephalitis virus(JEV) cell cultures and positive strains
      identified previously and determining the sensitivity with in vitro-transcribed
      RNA of serial dilutions. The GeXP system after optimization could amplify the
      specific fragments related to the viruses and exposed specifically a total of 13
      target genes out of eight types of arboviruses at the level of 10(2)
      copies/microL, and the findings suggest that the novel protocol we developed can
      be high-throughput and highly specific and sensitive as well as quickness in
      screening of the encephalitis viruses, and is promising in detection of
      encephalitis-associated viruses for molecular epidemiological studies.

PMID- 22416352
TI  - [Screening and identification of receptor reacting with nucleocapsid protein of
      duck enteritis virus].
AB  - To clarify the pathogenesis of Duck enteritis virus (DEV), the cDNA library of
      duck's liver infected by DEV and a bait plasmid containing DEV nucleocapsid
      protein (NP) gene were constructed, then the receptor was screened from the cDNA
      library plasmid by the yeast two-hybrid system and verified by GST pull-down
      test. The results showed that the capacity of the primary cDNA library was 1 x
      106 CFU with insertion size from 0.5 to 1 kb, and the bait plasmid of pGBKT7-NP
      showed no self-activation. The receptor reacting with DEV NP in duck liver was
      initially confirmed as the protein kinase C inhibitor (PKCI). These results
      provide new clues for further investigation on pathogenesis of DEV.

PMID- 22416353
TI  - [Construction and rescue of infectious cDNA clone of pigeon-origin Newcastle
      disease virus strain JS/07/04/Pi].
AB  - Based on the complete genome sequence of pigeon-origin Newcastle disease virus
      strain JS/07/04/ Pi(genotype VIb), nine overlapped fragments covering its full
      length genome were amplified by RT-PCR. The fragments were connected sequentially
      and then inserted into the transcription vector TVT7/R resulting in the
      TVT/071204 which contained the full genome of strain JS/07/04/Pi. The TVT/071204
      was co-transfected with three helper plasmids pCI-NP, pCI-P and pCI-L into the
      BSR cells, and the transfected cells and culture supernatant were inoculated into
      9-day-old SPF embryonated eggs 60 h post-transfection. The HA and HI tests were
      conducted following the death of embryonated eggs. The results showed that the
      allantoic fluids obtained were HA positive and the HA could be inhibited by anti
      NDV serum which indicated that the strain JS/07/04/Pi was rescued successfully.
      The rescued virus rNDV/071204 showed similar growth kinetics to its parental
      virus in CEF. The successful recovery of this strain would contribute to the
      understanding of the host-specificity of pigeon-origin NDV and to the development
      of the novel vaccines against the NDV infection in pigeons.

PMID- 22416354
TI  - [The progress of congenital cytomegalovirus infection and detection methods].
AB  - Cytomegalovirus infection is extremely common in the population, especially for
      newborns. Congenital CMV infection may cause central nervous system damage and
      other related diseases, thus potentially harmful. At home and abroad, some
      related research had been carried out on the incidence of disease, and a variety
      of detection methods had been developed. In this paper, the current situation of
      congenital cytomegalovirus infection and detection method is reviewed.

PMID- 22416355
TI  - [Advances in ubiquitin-like protein ISG15-mediated anti-viral response].
AB  - ISG15 is a 15kD ubiquitin-like protein (UBL) induced by interferon (IFN). ISG15
      can be covalently attached to proteins, which is called ISGylation process.
      ISGylation system contains ISG15, UBE1L, UBCH8 and HERC5 proteins, which are all
      essential for ISGylation. ISG15 and ISGylation system have been found to have
      anti-viral effects. A better understanding of how ISG15 mediates the anti-viral
      activity will provide insights for new anti-viral drugs development and new
      therapeutic strategies. The mechanisms underlying the ISG15 mediated anti-viral
      response have been explored extensively in recent years. This minireview
      summarized the research advances of how ISG15 mediated the anti-viral effects
      against different kinds of viruses.

PMID- 22416356
TI  - [Semen-derived enhancer of viral infection--a key factor in sexual transmission
      of HIV].
AB  - Semen-derived enhancer of viral infection(SEVI) is a peptide fragment (PAP248
      286) from prostatic acid phosphatase(PAP), which can enhance human
      immunodeficiency virus infection. The mechanisms of SEVI include: (1) SEVI with
      several cationic amino acid residues reduced electrostatic repulsion between HIV
      virus and the target cells; (2) The disorder state of SEVI in the human body
      fluids was helpful to the interaction between virus and the target cell
      membranes; (3) SEVI could capture HIV particles directly and speed the velocity
      of virus on the surface of the target cells and improve adsorption and fusion.
      Currently, the substances of inhibiting SEVI activity include: EGCG from green
      tea, small molecule compound of aminoquinoline Surfen, ThT analogs BTA-EG6. Those
      compounds might block the combination of HIV and SEVI or prevent the formation of
      amyloid fibers, and then reduce the enhancement of SEVI. The studies on the
      biological characteristics and mechanisms of SEVI have a big benefit for the
      prevention and treatment of HIV infection.

PMID- 22416357
TI  - [Feasibility study on global peste des petits ruminants eradication based on
      rinderpest eradication].
AB  - Eradication can be defined as permanent elimination of the occurrence of a given
      infectious disease. A joint FAO/OIE announcement of global rinderpest eradication
      was declared in 2011. The announcement from two international organizations
      indicates that the rinderpest virus, like the smallpox virus, will remain only in
      authorized laboratories. After rinderpest eradication, the relevant researchers
      shifted their focus on next target-peste des petits ruminants, since they mostly
      share similarities in such characteristics as etiology and pathology. This paper,
      on the one hand, analyzed objective and subjective factors in global rinderpest
      eradication, and on the other hand, reviewed the pros and cons of global peste
      des petits ruminants eradication.

PMID- 22416358
TI  - Universal salt iodization in the Central and Eastern Europe, Commonwealth of
      Independent States (CEE/CIS) Region during the decade 2000-09: experiences,
      achievements, and lessons learned.
AB  - BACKGROUND: By 2000, the global track record on universal salt iodization (USI)
      indicated 26% access to adequately iodized salt in the Central and Eastern
      Europe, Commonwealth of Independent States (CEE/ CIS) Region. OBJECTIVE: Aimed at
      extracting lessons learned, this study examined experiences, achievements, and
      outcomes of USI strategies in CEE/CIS countries during the subsequent decade.
      METHODS: Information from the design, timing, execution, outputs, multi-sector
      management and results of actions by national stakeholders yielded 20 country
      summaries. Analysis across countries used a LogFrame Analysis typical for public
      nutrition development. RESULTS: By 2009, USI strategies had reached the target
      and population iodine nutrition shown adequate levels in 9 countries, while in 6
      others, USI was close and/or population iodine status showed only minor
      imperfection. True USI, i.e., iodization of salt destined both for the food
      industry and the household, had been made mandatory in 13 of these 15 countries.
      In the Balkan area, USI and iodine nutrition advanced more than in CIS. Of the 20
      sample countries, 17 (85%) had exceeded the mark of 50% adequate access, while
      the overall regional score reached 55% by 2010. CONCLUSIONS: Experience from this
      region suggests that strong partnership collaboration, a new concept in post
      Soviet societies, was a major success factor. Voluntary iodization or focusing on
      household salt alone was less likely conducive for success. Achieving optimum
      iodine nutrition required the setting of proper iodine standard Weak political
      leadership insistence in the Russian Federation and Ukraine to embrace USI is the
      main factor why the region remains behind in the global progress.

PMID- 22416359
TI  - [Magnetocardiography in clinical practice: algorithms and technologies for data
      analysis].
AB  - This methodological work is the first part of series of papers dedicated to the
      modern perspective method of non-invasive diagnostics in cardiology-
      magnetocardiography. Definition of magnetocardiography method is given, levels of
      magnetocardiography data analysis as well as electrophysiological models are
      described. The most informative biomarkers and technologies of qualitative and
      quantitative interpretation of current density distribution maps and curves of
      total current magnitude are presented. The step-by-step algorithm, which was used
      for the MCG-data analysis, is proposed.

PMID- 22416360
TI  - [A modern view on the problem of the chronic pelvic pain at the women].
AB  - The article contains the basic causes and consequences of chronic pelvic pain
      (HPP) at the women. Shown that HPP - serious medical and social problem, which
      changes the psyche and behavior of women, violates her social adaptation.
      Pathogenesis HPP associated with persistent violations intraorganic and regional
      hemodynamics and hypoxia and acidosis that occur at the same time, cause
      degeneration of receptors and conduction system of pelvic organs, malnutrition
      solar cells and aortic nerve plexuses. Briefly described stages of HPP and this
      characteristic psychogenic pain as a diagnosis of exclusion. These basic ways to
      eliminate pain and pharmacological methods, physio and psychological action at
      HPP.

PMID- 22416361
TI  - [Atopic dermatitis: a modern view of pediatricians and pediatric allergologist].
AB  - The article presents the views of pediatric allergologist on the problem of
      atopic dermatitis/ atopic eczema in children. Atopic dermatitis (AD) is
      considered from a modern viewpoint of allergic 'march', which is characteristic
      (typical) for children with atopy. These data indicate to systemic nature of
      atopic 'march', the first step of which is atopic eczema. Further evolution of
      atopic dermatitis leads to a transformation of it in other atopic diseases-
      allergic rhinitis and bronchial asthma; this fact indicates that
      immunopathological disorders are united in these diseases and it conditions the
      possibility of prevention. It has taken into consideration the systemic nature of
      atopic diseases, combined therapy is great important and has to include not only
      basic local therapy, in particular topical corticosteroids (mometasone furoate-
      Elokom) during the exacerbation, and the systematic elimination of trigger
      factors, diet, the removal of the digestive system dysfunctions and the imbalance
      of vitamins. A long-time systemic basic therapy by H1-antihistamines of second
      generation, such as desloratadine (Aerius) takes a special place in the treatment
      of atopic dermatitis.

PMID- 22416362
TI  - [Meningococcus infection: problem actuality].
AB  - The data of literature are stated concerning the population's sickness of
      meningococcus infection in Ukraine and the world. The meningococcus infection is
      one of the most actual problems of medicine.

PMID- 22416363
TI  - [Thromboprophylaxis in patients with multiply myeloma who receives chemotherapy
      with thalidomide].
AB  - Achievements of world practice about development and prophilaxis of tromboembolic
      events (VTE) in cancer patients. Particular attention is paid to prevention of
      VTE in patients with multiply myeloma who receive chemotherapy with Thalidomide.

PMID- 22416364
TI  - [Cardiotoxicity of conservative treatment of solid tumors].
AB  - With an increasing number of long-term breast cancer survivors, the number of
      patients experiencing anthracycline-induced cardiotoxicity increas too.
      Anthracycline--and nonanthracycline-induced cardiac toxicity--clinically
      significant and frequent adverse event of conservative treatment of cancer.
      Echocardiogram and multigated acquisition (MUGA) scan--modalities that may
      overlook early changes that could identify patients at risk for anthracycline
      related cardiotoxicity. However, monitoring cardiac function before and during
      therapy, continuous infusions of drugs, limiting lifetime anthracycline dose,
      using cardioprotectants such as dexrazoxane, and developing lipid formulations,
      may decreased risk of cardiotoxicity.

PMID- 22416365
TI  - [Some peculiarities of aetiological factors of chronic pyelonephritis development
      in the childhood].
AB  - The paper provides literature data concerning the role of heredity, anatomico
      physiological peculiarities which contribute to the chronic pyelonephritis
      formation in the childhood. The conditions of the infectious-inflammatory process
      development in the urinary tract are specified and some reasons of its
      chronization are mentioned. The peculiarities of the immunological reaction are
      analysed, as well as the role of nonimmune mechanisms, such as the lipid
      peroxidation process during the pyelonephritis development in the childhood.

PMID- 22416366
TI  - [Postprandial hemodynamic reactions of patients with ischemic heart diseases and
      chronic pancreatitis].
AB  - The results of the study hemodynamic changes in postprandial period in patients
      with coronary heart disease (CHD) and chronic pancreatitis (CP). It is
      established that patients with CHD and HP reduced pumping function of the heart
      after a meal in patients with isolated CP. In patients with isolated coronary
      artery disease marked increase in the pumping function of the heart. Reduced
      pumping function in patients with CP due to reduced end-diastolic index. All
      three groups are not significant differences in terms of diastolic function. The
      main differences between groups were found in the subgroup of patients with CP at
      the time of the survey was in acute phase. It is in this subgroup, a significant
      decrease not only the pump, but also inotropic cardiac function.

PMID- 22416367
TI  - [The effectiveness of pioglitazone in the treatment of patients with coronary
      heart disease on the background of metabolic syndrome].
AB  - We investigated the effectiveness of pioglitazone in the treatment of patients
      with coronary heart disease in combination with MS. In the conduct of research
      revealed that the addition to standard therapy in patients with coronary heart
      disease on the background of metabolic syndrome pioglitazone led to a reliable
      slight decrease in body weight, BMI, hip circumference, waist their relationship.
      Receiving pioglitazone also significantly reduces the concentration of
      immunoreactive insulin and blood glucose levels, significantly altered lipid
      metabolism, which generally leads to a lower level of systemic inflammation,
      metabolism and reduces the severity of insulin resistance. This allows you to
      recommend the inclusion of pioglitazone in complex coronary heart disease and
      metabolic syndrome.

PMID- 22416368
TI  - [Informational content in diagnostics for 13C-bicarbonate breath test in
      determining the basal metabolic rate and energy expenditure].
AB  - This article is devoted to the new method for the determination of basal
      metabolism using 13C-bicarbonate breath test compared to the method of Harris
      Benedict in healthy and patients with impaired thyroid function. The problems of
      diagnostic information content, features and advantages of the clinical
      application of 13C-bicarbonate breath test compared to the method of Harris
      Benedict.

PMID- 22416369
TI  - [The role of splenectomy in the treatment of idiopatic thrombocytopenic purpura].
AB  - Based on the earlier published data this article describes the role of the spleen
      in the development of some hematological diseases, the main of which is
      idiopathic thrombocytopenic purpura (ITP). The authors emphasize the role of
      splenectomy in the treatment of this disease. At 178 splenectomies performed at
      the clinic, 23,6 % of operations were carried out for hematological diseases, and
      among them 42,8 %--for ITP. The authors share their immediate and remote results
      of the treatment.

PMID- 22416370
TI  - Pathomorphosis of the classical Caposi's sarcoma: anamnesis, catamnesis, clinics.
AB  - The analysis of 40 histories of disease of the patients with histologically
      confirmed diagnosis of classical KS for the period from 1991 to 2006 has shown,
      that under conditions of our region the clinical picture of classical KS
      undergoes changes. The first signs of disease are registered at 35% of the
      patients at the age under 50 years, among the first manifestations of disease in
      20% of cases the swellings meet, 17,5% have variants with atypical localization
      on the face, head, neck, there are cases of transition of chronic process into
      subacute with absence of correlation between prevalence of process and acuteness
      of its development. The average age of the patients to the beginning of disease
      was 49,6 years.

PMID- 22416371
TI  - [Influence Mildrocard on the morfo-functional condition of cardio-respiratory
      system at patients with chronic heart failure with concomitant chronic
      obstructive pulmonary disease].
AB  - In paper influence of a cytoprotective drug "Mildrocard" on morfo-functional
      condition of cardiorespiratory system at patients with chronic heart failure with
      concomitant chronic obstructive pulmonary disease is estimated. It is
      established, that joining "Mildrocard" to complex therapy associated to pathology
      promotes reduction clinical display of heart failure, shows cardioprotective and
      pulmoprotective effects.

PMID- 22416372
TI  - [Experience in complex therapy ribavine chronic viral hepatitis C].
AB  - In 72 patients with chronic hepatitis C aged 18 to 62 years evaluated the
      clinical efficacy Ribavine in combination therapy with interferon-alpha. The
      safety, good tolerability and efficacy Ribavine. Persistent virological and
      biochemical response in the application of interferon-alpha and Ribavine obtained
      from 47,5 to 53,1%. Recurrence rate was 32,5% in patients with genotype 1 and
      21,9% with genotype 2 and 3. Side effects of Ribavine are reversible and leveled
      after the completion of therapy.

PMID- 22416373
TI  - [Clinical efficiency of Vasonat in neurometabolic therapy of patients with
      ischemic stroke at early rehabilitation period].
AB  - Research of efficiency and safety of Vasonat has been carried out. 31 patients
      aged 46-75 years who had had hemispheric athero- thrombotic or hemodynamic
      schemic stroke with moderate severity and being treated in 2-5-month of early
      rehabilitation period have been observed. The control group of patients received
      placebo. Results of the study, 4 weeks treatment using Vasonat in the dosage of
      500 mg/day have shown positive effect on common signs of the disease by
      decreasing headache intensity, dizziness, a nausea, and on focal neurological
      symptoms by decreasing hemiparesis degree; psychoemotional and mnestic activity
      (main memory and attention) improved as well. It was more distinct in patients
      with localization of the stroke in the right hemisphere of the brain. It was also
      noted more rapid improvement of motion function and quality of life of patients.

PMID- 22416374
TI  - The methods of fractal analysis of diagnostic images. initial clinical
      experience.
AB  - The report describes the application of fractal analysis in complex systems of
      visual diagnostics in order to expand its diagnostic capabilities by increasing
      the information content for intelligent decision modeling to reduce subjectivity
      in the perception and interpretation.

PMID- 22416375
TI  - [Genetic performance criteria for valproate in patients with epilepsy].
AB  - We found a clear correlation between the presence of the CC genotype and genotype
      combination CC and CT P-glycoproteins rs1045642 and rs1128503 with
      farmakorezystentnistyu data of patients with valproate (P < 0,01). Also, based on
      studies demonstrated that the presence of polymorphism TT P-glycoproteins
      rs1045642 is a positive criterion of forecast performance valproate in a
      particular patient with epilepsy. We use the definition of P-glycoproteins SNPs
      rs1045642 and rs1128503 to accelerate the selection of adequate antiepileptic
      that reduces the selection of adequate treatment tactics in a particular patient.
      This in turn will prevent the development epileptohenezu that increase the
      likelihood of full kurabelnosti patient.

PMID- 22416376
TI  - [Physical work capacity of patients with chronic alcoholism and the factors
      limiting it].
AB  - Chronic alcoholism causes decreased physical work capacity and tolerance to
      physical exertion, due to uneconomic operation of cardiovascular system and
      myocardial lesions in this disease.

PMID- 22416377
TI  - [Foundation for the revival of prevention of occupational diseases].

PMID- 22416378
TI  - [Morphologic characteristic of chronic toxic hepatitis for treatment with
      Neoselen].
AB  - The purpose of the given research work was to study the features of morphologic
      changes arising for treatment of chronic hepatitis with Neoselen. It was
      established a picture of chronic active hepatitis in the liver of rats with the
      following development of chronic persisting hepatitis by the 40 daily
      administration of heliotrine and its transmission into cirrhosis in a certain
      part of animals. Hepatic cirrhosis has a small nodal portal character by its
      pathognomonic morphologic signs. A noticeable remittance of destructive necrotic
      changes in hepatic parenchymatous elements and reduction in a volume of
      proliferative inflammatory infiltration with an acceleration in process of its
      fibrozation in only periportal zones of hepatic lobules found to be for treatment
      of chronic hepatitis with Neoselen. That prevents from transmission of chronic
      hepatitis into cirrhosis in a greater part of animals that is a morphologic
      evidence of importance of selenium in a restorative process of biologic membranes
      and its involvement in a remittance process of destructive and inflammatory
      changes in the liver and prevention from development of agressive hepatitis and
      its transmission into cirrhosis.

PMID- 22416379
TI  - [Methodological approaches to forecasting of disability dynamics in Ukraine].
AB  - Estimated the dynamics of indexes of primary disability of adult and able to work
      population for 2000-2009 on the whole on Ukraine and on administrative
      territories. For development of the methodological going near prognostication of
      disability used the methods of mathematical statistics: analysis of sentinel rows
      and regressive analysis. Indexes over of disability during ten years are brought
      as sentinel rows through the system of sentinel parameters and supervision; the
      models of linear trends are built, their adequacy and authenticity are tested, a
      prognosis is certain. Creation of the improved methods of analysis gives an
      opportunity to extract regions which it is necessary in, first of all, to study
      reasons and problems of increase of disability; to work out the purposeful
      measures of warning of her increase.

PMID- 22416380
TI  - [Availability of patients living in rural areas, to have surgical method of
      treatment of cataract and glaucoma].
AB  - Using modern surgical treatment on patients that live in rural areas, with
      cataract and glaucoma is not sufficient. There is insufficient expertise of
      ophthalmologists, low level of human, logistical and financial resource support
      for eye hospitals, low level of motivation and socio-psychological problems among
      patients, creating a favorable situation in Ukraine for further growth of low
      vision and blindness in rural areas. Institutional solutions of existing problems
      are proposed.

PMID- 22416381
TI  - [Clinical and epidemiological analysis hospitalization indicators Ministry's of
      Defense of Ukraine servicemen with reactive arthritis].
AB  - Our researches showed high occurrence of the reactive arthritises among
      servicemen Ministry of Defense of Ukraine and improvement of the treatment
      outcomes of this patients during the last years.

PMID- 22416382
TI  - [Mistletoe lectins--antitumor effect and mechanism of action].

PMID- 22416383
TI  - [Detection and treatment of ductal carcinoma of the breast].

PMID- 22416384
TI  - [Minimal breast carcinomas].

PMID- 22416385
TI  - [Cryosurgical treatment for prostate cancer: current state].

PMID- 22416386
TI  - [Epigenetic aspects of early lymphogenic metastasis in breast cancer].
AB  - Metastasizing is one of the key stages in tumor development. Understanding this
      process is necessary for effective diagnosis, therapy and prediction of clinical
      outcome. Some recent data suggest the possibility of metastatic phenotype cells
      appearance at the early stages of tumor evolution in contravention with generally
      accepted hypothesis of linear metastatic process development. In this study we
      have performed a comparative analysis of the array-based DNA methylation profile
      in biopsy samples of patients with benign breast disorders, breast cancer and
      lymphogenous metastases. In some cases the biopsy samples dated back to different
      stages of the same tumor. For the analysis the GoldenGate Methylation Cancer
      Panel I was used. The DNA methylation level in 1,505 CpG-sites was similar in
      samples from patients with benign breast disorders and lymphogenous metastases.
      Our data support the hypothesis of the early appearance of cell clones
      responsible for the tumor limphogenous dissemination. Epigenetic component
      apparently plays an important role in this process.

PMID- 22416387
TI  - [Enzymes of estrogen metabolism in breast cancer and their correlation with
      outcome].
AB  - The biopsy samples of 85 patients with breast cancer (BC) stage T1-3N0-3M0 were
      studied for estrogen metabolism enzymes (aromatase, 2,4-estrogene hydroxylase and
      gluthathion transferase) activity. This data was analyzed in relation to disease
      outcome. Aromatase activity in cancer tissue less than 20 fmol/ mg protein/h and
      2,4-estrogene hydroxylase activity more than 230 pmol/mg protein/h proved to be
      the independent and significant predictors associated with worse relapse-free
      survival. The activity of gluthathiontransferase in tumor tissue less than 40
      mkmol/mg protein/h is associated with worse metastatic-free survival. The
      activities of estrogen metabolism enzymes may be used as additional prognostic
      markers for breast cancer outcome.

PMID- 22416388
TI  - [Role of computerized tomography in the diagnosis of gastrointestinal stromal
      tumors].
AB  - In this study we present an analysis of our own data on computerized tomography
      (CT) employment in patients with gastrointestinal stromal tumors (GIST) and the
      review of the literature. The CT data for 21 patients with GIST was compared with
      operation and morphology data. Difficulties of GIST timely diagnostic are
      described.

PMID- 22416389
TI  - [Laparoscopic surgery for treatment of endometrial cancer].
AB  - Surgery is the cornerstone of the treatment of endometrial cancer. With
      introduction of new technologies the laparoscopic intervention becomes
      increasingly popular for treatment of endometrial cancers. Forty five patients
      with endometrial cancer were operated in N.N. Petrov Research Institute of
      Oncology from September 2011 to March 2011. Laparoscopic hysterectomy with
      appendages was performed in 30 patients (66.7%), in 14 (66.7%) patients was also
      performed pelvic lymphadenectomy and in 1 (2.2%) case additional omentectomy was
      required. There were no intraoperative complications. The postoperative period
      was characterized by early mobilization, satisfactory intestinal peristaltic in
      the first 24 hours, minimal complication rate and absence of contraindications
      for adjuvant radiotherapy.

PMID- 22416390
TI  - [Effectiveness of aromatase inhibitors in comparison with metformin for
      neoadjuvant treatment in patients with endometrial cancer].
AB  - We compared the efficacy of endometrial cancer neoadjuvant treatment in 38
      patients receiving nonsteroid (letrozol, anastrozol) or steroid (ekzemestan)
      aromatase inhibitors and 12 patients receiving metformin. The changes in glucose
      metabolism were revealed in 26.3% of patients treated with aromatase inhibitors
      and 16.7% of patients treated with metformin. However, comparison of endometrial
      thickness (M-echo signal) data, postoperative data on favorable differentiation
      grade changes rate and proliferative activity (Ki-67 expression) revealed the
      superiority of 2-4 weeks aromatase inhibitors course in comparison with 2-9
      (average 5.3 +/- 0.7) weeks metformin treatment.

PMID- 22416391
TI  - [Expression of sex hormones receptors in leiomyoma with uncertain potential of
      malignancy and endometrial leiomyosarcoma: differentiatial diagnosis and
      prognostic significance].
AB  - A retrospective evaluation of progesterone (PR) and alpha-estrogen (ER)
      expression was carried out in 16 patients with smooth muscle tumors with
      uncertain potential of malignancy (STUMP) and 76 patients with uterine
      leiomyosarcoma (ULMS). PR expression was observed in 100% of intact myometrium
      and leiomyoma samples, while ER was expressed only in 37.1 +/- 4.2% and 23.5 +/-
      4.1% of samples. In STUMP samples PR expression was observed in 66.7 +/- 11.7% of
      cases, in ULMS samples in 50.5 +/- 5.7% of cases. However, there was an inverse
      correlation between malignancy grade and sex hormones expression, although the
      number of positive cells and staining intensity didn't prove to be independent
      risk factors. The patients with ULMS G1 and STUMP expressing sex hormones have
      favorable prognosis, while negative receptor status of STUMP tumors is the marker
      of the worse prognosis.

PMID- 22416392
TI  - [Positron emission tomography with 18F-FDG compared with proliferative activity
      of tumor cells in different subtypes of non-Hodgkin lymphoma].
AB  - In the course of this study we determined the ability of positron emission
      tomography (PET) with the 18F-FDG to detect non-hodgkin lymphoma lesions, assess
      their proliferative activity and differentiate aggressive tumors from indolent.
      Tracer uptake in lymphoma was evaluated semiquantitatively by calculation of
      standardized uptake values (SUV). It was compared with tumor grade and
      proliferation fraction determined by Ki-67 staining. In patients with indolent
      lymphoma, mean SUV was 2.5 +/- 0.6. In patients with aggressive lymphoma a
      significantly higher 18F-FDG uptake was observed (mean SUV was 8.1 +/- 1.3).
      Linear regression analysis indicated significant correlation of 18F-FDG uptake to
      biopsy samples proliferation fraction in patients with diffuse large B-cell
      lymphoma (r = 0.55, p = 0.05) and indolent non-Hodgkin's lymphoma (r = 0.7, p <
      0.05). In this clinical study 18F-FDG uptake correlates with the aggressiveness
      of malignant lymphomas and with biopsy samples proliferative activity.

PMID- 22416393
TI  - [Efficacy of standard docetaxel and metronomic cyclophosphamide chemotherapy in
      patients with hormone-resistant prostate cancer: comparative analysis].
AB  - Fifty five patients with hormone-resistant prostate cancer were included in this
      retrospective controlled study. Chemotherapy with intravenous docetaxel (75 mg/m2
      for 21 days) was performed in 30 patients, 25 patients received metronomic oral
      therapy with cyclophosphamide (50 mg/day). The central objective of this study
      was the comparison of overall survival in these groups. Pain management
      effectiveness, quality of life and PSA level were also compared. In docetaxel
      group the median overall survival was 15.9 +/- 1.7 months, in cyclophosphamide
      group 15.4 +/- 2.2 months (p = 0.5). Frequency of PSA level decrease was 76.7%
      and 44%, PSA response to therapy was observed in 46.7% and 12% of patients (p =
      0.04 and p = 0.02). In docetaxel group pain reduction was achieved in 42.9% and
      in cyclophosphamide group in 31.3% of cases (p = 0.60). Grade III-IV
      hematological toxicity was observed only in docetaxel group (33% of patients), in
      16.7% of patients receiving docetaxel the therapy had to be ceased due to adverse
      effect. Quality of live was improved in 26.7% of patients receiving docetaxel and
      in 16% of patients receiving cyclophosphamide.

PMID- 22416394
TI  - [Laboratory evaluation of TGFbeta1, IL-10, VEGF levels in vivo and in vitro in
      patients with solid tumors].
AB  - Tumor cells can acquire the mechanisms of immune response evasion. One of these
      mechanisms is synthesis and secretion in the microenvironment of
      immunosuppressive factors able to block immune cells maturation and function. We
      investigated plasma levels of TGFbeta1 and IL0 in 10 healthy volunteers and 114
      patients with solid tumors (breast cancer--24, gastrointestinal tumors--27, renal
      cell carcinoma--15, lung cancer--9, ovarian cancer--13, cutaneous melanoma--18,
      primary multiple tumors--2, prostate cancer--6). TGFbeta and IL10 concentration
      in supernatants of 37 primary cultures (cutaneous melanoma, renal cell carcinoma
      and prostate cancer) and 10 cultures of melanoma during cultivation were also
      studied. VEGF was determined by immunocytochemistry staining in 15 melanoma
      culture specimens. The lowest level of TGFbeta1 was documented in rectal cancer
      patients, 30.05 +/- 12.30 ng/ml (p < 0.05), the highest in renal cell cancer and
      pancreatic cancer patients, 145.61 +/- 11.32 and 146.15 +/- 30.56 ng/ml (p <
      0.001), respectively. Primary cultures of tumor cells can synthesize traceable
      amounts of TGFbeta1 and IL10. Cultures of cutaneous melanoma, renal cell
      carcinoma and prostate cancer cells did not change expression level of IL-10
      after several passages. VEGF was expressed in 20% of cutaneous melanoma cultures.
      We suppose that tests for TGFbeta1, IL10 and VEGF in culture supernatants from
      tumor cell lines, on the surface of the cells purposed for cancer vaccines and in
      serum of patients to be vaccinated are potentially useful.

PMID- 22416395
TI  - [Synergism of antitumor activity of gemcitabine and dioxadet in mice with ascitic
      Ehrlich's tumor].
AB  - Antitumor activity of a new cytostatic drug combination of gemcitabine and
      dioxadet have been studied in 86 female SHR mice transplanted with 5 x 10(6) of
      ascitic Ehrlich's tumor cells each. All mice received a single injection of
      gemcitabine, dioxadet on combination 48 hams after tumor cells introduction. In
      first series, experimental animals received maximal tolerable dose of gemcitabine
      (25 mg/kg) and one half of dioxadet maximal tolerable dose (2.5 mg/kg). In the
      second series of experiments, the animals received 5 mg/kg of dioxadet along with
      the same gemcitabine dose. Effect of drugs was compared using the time to ascites
      detection, body weight increase, and survival time. Gemcitabine and dioxadet
      administered separately and in combination inhibited the growth of ascitic
      Ehrlich's tumor in the mice. In both series of experiments antineoplastic
      activity of gemcitabine and dioxadet combination was significantly higher in
      comparison to the control groups receiving these drugs separately. The highest
      antineoplastic activity of the gemcitabine and dioxadet combination was observed
      when the maximal tolerable doses of both drugs was applied. However, the tumor
      cells growth was also significantly inhibited in mice receiving half of dioxadet
      dose. Synergism of antitumor activity of gemcitabine and dioxadet was not
      accompanied by appreciable increase in toxicity.

PMID- 22416397
TI  - [Role of arterial embolization in bilateral kidney cancer].
AB  - From 1995 to 2006 we performed embolisation in 9 patients with bilateral kidney
      cancer. Embolization of kidney with smallest cancer was done at the first stage
      with subsequent embolisation of tumor in the contralateral kidney. Technically
      all procedures were successful and were performed without complications.
      Operative intervention on the contralateral kidney was undertaken 1-4 months
      after embolization in 8 patients. Five patients are alive for 5 and more years.
      Four patients died in 34-49 months after intervention. Selective embolization is
      a safe and effective modality which expands our abilities to treat patients with
      bilateral kidney cancer. Embolization can be used as single treatment modality
      and in combination with subsequent surgery.

PMID- 22416396
TI  - [Antitumor activity of dioxadet compared with cisplatin on ascitic ovarian tumor
      in rats].
AB  - Antitumor activity of dioxadet in comparison with cisplatin was studied on the
      model of ascitic ovarian tumor in 32 female Wistar rats. Ascitic ovarian tumor
      was transplanted intraperitoneally 0.5 ml per rat dissolved by saline in ratio 1
      to 4. Dioxadet (1.5 mg/kg b.w.) and cisplatin (4.0 mg/kg b.w.) were administered
      intraperitoneally at their single maximal tolerable doses 48 hours after tumor
      cells transplantation. For drug activity estimation time to ascites detection and
      survival time values were used. In control group without no treatment the time
      till ascites occurrence and median life span were 5.4 +/- 0.25 and 7.5 days,
      correspondingly. In comparison with the control group dioxadet increased the
      average time of ascites occurrence and median of life span by 30% and 113% (p <
      0.05), cisplatin increased these parameters by 28% and 147% (p < 0.05). Hence,
      antitumor activity of dioxadet is comparable with cisplatin activity for
      intraperitoneal therapy of the ascitic ovarian tumor.

PMID- 22416398
TI  - [Support of hematological homeostasis during chemotherapy with taxanes].
AB  - Study group consisted of 84 oncological patients with various tumor localization
      that received chemotherapy with taxanes. Medium follow up was 32.1 +/- 2.1
      months. All patients had morphologic verification of the process. Distribution
      according to tumor localization was as follows: breast cancer--60 (71.4%),
      ovarian cancer--13 (15.5%), lung cancer--7 (8.3%), other localizations--4 (4.8%).
      Age varied from 22 to 73 years old. All patients had normal hematological status
      and survival expectation more than 3 months. Hematological complications were
      mentioned after the first cycle of chemotherapy in 70% cases.

PMID- 22416399
TI  - [Surgical treatment of embolism threatening formations of the right parts of the
      heart].
AB  - Operations were fulfilled on 42 patients with embolism threatening formations of
      the right parts of the heart. An episode of pulmonary arteries was in the
      anamnesis of 11 patients. In all cases the operations were fulfilled under
      conditions of extracorporeal circulation and cardioplegia. One patient died at
      the hospital. Lethality was 2.33%.

PMID- 22416400
TI  - [The course of the postoperative period in patients with cerebral gliomas after
      different volumes and kinds of surgery].
AB  - The investigation included 340 patients with cerebral gliomas. Under analysis
      there were age, gender, neurological status and Karnovsky status before and after
      operation, localization of the tumor, type and volume of surgical intervention,
      postoperative complications. It was shown that radical extirpation of glial
      formations facilitated more favorable course of the postoperative period. Partial
      ablation of gliomas is associated with greater risk of the development of
      postoperative complications and neurological dysfunctions. As the main method of
      surgical treatment of patients with gliomas located in the functionally
      significant and deep areas of the brain stereotaxic cryotomy is thought to be
      indicated.

PMID- 22416401
TI  - [Radiofrequency-assisted atypical resections of the liver for the colorectal
      cancer metastases].
AB  - The authors presented direct results of atypical resections of the liver for the
      colorectal cancer metastases fulfilled on 55 patients with the application of
      radiofrequency apparatus for the period from 2006 through 2010. The method used
      resulted in creation of 2.0 cm coagulation area which allowed dissection of the
      liver tissue practically without bleeding.

PMID- 22416403
TI  - [Treatment of bleedings from cystic formations of the pancreas].
AB  - Treatment of 10 patients with bleedings from the pancreatic cysts was analyzed.
      Angiography with endovascular occlusion of the source of bleeding was used in 4
      patients. Hemostasis was achieved in 2 patients. Emergency operations were made
      on 7 patients with continuing and repeated bleedings, and unsuccessful attempts
      of roentgen-endovascular treatment. Two patients after correction of anemia were
      subjected to planned operations according to the indications accepted for chronic
      cystic pancreatitis. The operation allows reliable liquidation of the source of
      bleeding and the symptoms of chonic pancreatitis.

PMID- 22416402
TI  - [Infusion correction of bile outflow and endotoxicosis in patients with
      mechanical jaundice].
AB  - The investigations were performed in 139 patients divided into 3 groups and who
      were given similar volume of infusion therapy (1600 ml/day). In the first group
      consisting of 54 patients the solution of infusion therapy included the Ringer
      solution and 10% of glucose solution in the ratio 1:1. In the second group (37
      patients) the infusion therapy was performed with a solution of sterofundin-G-5.
      In the third group (48 patients) remaksol in dose 800 ml/day was included in
      infusion therapy. The inclusion of sterofundin-G-5 and remaksol in the infusion
      therapy increased the rate of bile outflow at the early postoperative period as
      compared with the solutions of Ringer and 10% of glucose. Remaksol is better for
      arresting endotoxicosis and bile excreting function of the liver as compared with
      infusion of sterofundin-G-5.

PMID- 22416404
TI  - [The application of immobilized forms of sodium hypochlorite in complex treatment
      of diffuse purulent peritonitis].
AB  - Complex examination and the following treatment of 380 patients with diffuse
      purulent peritonitis were analyzed. The patients were divided into 2 groups. The
      first group included 245 patients to whom the sanitization of the abdominal
      cavity used traditional antiseptics. The main group included 135 patients to whom
      the immobilized form of sodium hypochlorite in the carboxymethyl cellulose was
      introduced instead of aqueous solution. An original method of sanitization of the
      abdominal cavity allows 1.2-1.5 times decreased degree of endotoxicosis, 2-2.5
      times improved the motor-evacuatory function of the intestine in different forms
      of treatment of peritonitis. In the main group of patients the number of
      postoperative complications was 10% less, lethality was 8.2% less.

PMID- 22416405
TI  - [Up-to-date techniques of diagnostics, prognosis and prophylaxis of dysfunction
      of the renal allotransplant].
AB  - On the basis of their experience with 530 kidney transplantations and literature
      data the authors argue the necessity of careful assessment of the kidney
      allograft state at all stages of its life. An accent is thus done on the
      necessity of the complex diagnostics with using noninvasive and invasive methods
      that will facilitate the kidney allograft dysfunction prediction and prevention,
      and longer time of the kidney allograft survival.

PMID- 22416406
TI  - [Changes in podometric indices in women during pregnancy and at the puerperal
      period].
AB  - Under investigation there were podometric indices (width of the foot arch, foot
      length, foot arch height) in different body positions and load. Considerable
      changes of functions of the locomotor system were revealed which require
      appropriate correction.

PMID- 22416407
TI  - [Comparison of a medical effect of cryosupernatant and fresh frozen plasma used
      in complex treatment of patients with severe combined traumas].
AB  - Results of complex treatment of severe combined traumas were compared in 56
      patients with using cryosupernatant plasma fraction (CSPF) and fresh frozen
      plasma--in 112 patients. Better positive dynamics of some laboratory indices was
      noted as well as lower risk of the development of thromboses, less lethality and
      better outcomes of the disease when using CSPF. It can be used instead of fresh
      frozen plasma in complex treatment of patients with severe combined traumas and
      coexisting DBC-syndrome.

PMID- 22416408
TI  - [Injury to the liver in patients with severe combined traumas].
AB  - Experience with treatment of 220 patients with a severe combined trauma who were
      subjected to surgical intervention on abdominal organs was analyzed. In 164 of
      them (74.8%) there was a closed trauma, in 56 (26.2%) abdominal wounds were
      diagnosed. Injuries of the liver resulting from the closed trauma of the abdomen
      were revealed in 41 (25.6%) patients. For the assessment of severity of the
      injury and determination of the strategy of treatment the authors have developed
      a classification of liver injuries.

PMID- 22416409
TI  - [Surgical treatment of injuries of the large vessels].
AB  - The authors present an experience with treatment of 99 patients with primary
      wounds of main vessels. The age of the patients was from 42 through 83 yeas. In
      85 patients there were stab wounds, 9 patients had gunshot wounds, in 5 patients
      injuries of the main vessels were results of blunt trauma. Eleven patients were
      admitted in the condition of shock of I degree, 27--II degree and 46--III degree,
      15 patients were in the terminal state. Wounds of the aorta were diagnosed in 10
      patients, 4 patients died. Injury of the superior vena cava was found in 4
      wounded patients, nobody died. Postcava was injured in 11 patients, 6 patients
      died. Wounds of the portal vein were diagnosed in 8 patients, 7 of them died.
      Operations were fulfilled on 19 patients with wounds of the neck and injuries of
      the large vessels. One patient died. Injuries of the large vessels of the upper
      and lower extremities took place in 15 patients. Nobody died.

PMID- 22416410
TI  - [The role of central lymphadenectomy in treatment of patients with thyroid
      cancer].
AB  - Direct and long-term results of surgical interventions for differentiated cancer
      of the thyroid gland supplemented with lymphadenectomy on the tumor side were
      studied on the material of 1136 patients. As a group of comparison there was a
      group of 303 patients with similar histological diagnoses, gender and age and
      distribution of carcinomas by stages in which the ablation of para- and
      pretracheal lymph nodes was not fulfilled by any reasons. The investigation gives
      proofs of the necessity to perform central lymphadenectomy simultaneously in all
      primary operations for differentiated cancer of the thyroid gland.

PMID- 22416411
TI  - [Surgical treatment of posttraumatic deformity of the orbital floor].
AB  - The article is devoted to an actual problem of surgical treatment of patients
      with posttraumatic deformities of the orbital floor. On the material of 21
      observations it was shown that for the successful treatment of deformities of the
      orbit bottom autogenous costal cartilage graft should be used as a plastic
      material. Removal of enophthalmos in longstanding fractures can be reached only
      by reducing the volume of the orbit which can be achieved by retrobulbar
      placement of the graft. An analysis of the results demonstrated high efficiency
      of this method in the treatment of such patients.

PMID- 22416412
TI  - [Specific features of anesthetic management of surgical treatment of malignant
      tumors of the skull base].
AB  - Neurosurgical interventions on the skull base including craniofacial block
      resections were fulfilled on 36 patients aged from 16 through 73 years.
      Preoperative management of the patients was made mainly at the intensive therapy
      room. It included correction of water-electrolyte, protein metabolism, anemia.
      The key moments in the anesthetic management of such operations were maintenance
      of an adequate level of neurovegetative blockade, sufficient level of volemia by
      means of creating hypervolemic hemodilution, prophylactics of air embolism.

PMID- 22416413
TI  - [25 year experience with using surgical correction of dislipidemia in treatment
      of patients with atherosclerosis].
AB  - An analysis of results of using partial ileoshunting for the treatment of
      dislipidemia in 159 patients with atherosclerosis has shown that operation of
      partial ileoshunting has an obligatory, pronounced and lifelong lipidcorrecting
      effect. An antiatherogenic effect of the operation of partial ileoshunting is
      manifested as the improvement of the clinical course of the disease caused by
      atherosclerosis, by less number of thrombotic complications of atherosclerosis
      and less lethality from cardio-vascular diseases. At a longer follow-up period,
      the efficiency of partial ileoshunting as a means of secondary prophylactics of
      atherosclerosis is confirmed but in case of liquidation after operation of
      dislipoproteidemia.

PMID- 22416414
TI  - [First experience with submucous endodissection of the duodenum bulb carcinoid].

PMID- 22416415
TI  - [Successful treatment of gigantic extragenital endametrioid cyst with ingrowth
      into the duodenum and pancreas].

PMID- 22416416
TI  - [Hamartoma. Difficulties in the diagnosis. Ways of solution].

PMID- 22416417
TI  - [Portraits of N.I Pirogov in fine arts of I.E. Repin (on 130 years of creation
      "the portrait of surgeon N.I.Pirogov"].

PMID- 22416418
TI  - [K.M. Sapezhko--the author of the method of urethroplasty of the oral cavity
      mucous membrane].

PMID- 22416419
TI  - [Mechanisms of the development of polyorganic insufficiency in shockogenic
      trauma: clinical approach to the problem].

PMID- 22416420
TI  - [Unsolved questions of treatment of choledocholithiasis].

PMID- 22416421
TI  - [Comparative characterization of different methods of perineum biopsy of the
      prostate].

PMID- 22416422
TI  - [Endoprosthesis of the hip joint in children and juveniles].

PMID- 22416423
TI  - [The perspectives of development of molecular diagnostics of allergy in the
      microarray format].
AB  - All over the world, many people suffer of various forms of allergy. The timely
      and accurate diagnostics of allergic sensitization is able to prevent the
      complications and to select a proper mode of therapy. Over the last century, were
      isolated and characterized hundreds of specific allergenic substances, in the
      form of extract mainly In 1966, the class E immunoglobulins were discovered and
      their role in the formation of hypersensitivity type 1 was explained. Hence, the
      application of techniques of specific sensitization diagnostics became possible
      in vitro. The diagnostic systems based on the principles of immune-enzyme assay
      on plate. The appearance and rapid development of microarray technology in the
      end of XX century provided an opportunity to implement mass screening of specimen
      on hundreds and thousands markers. The given technique seems to be promising for
      carrying out a voluminous and rapid allergoscreening. A prototype specimen of
      test system was developed in the form of microarray with 15 immobilized
      allergens. The 16 samples of blood serum of patients with allergic diseases were
      analyzed. The findings demonstrated a high correlation with reference
      allergosorbent test. The analysis mode implies a direct immobilization of
      allergen on phase. This approach makes the most of standard extracts unsuitable
      due to the presence of considerable amount of non-allergenic "ballast" proteins.
      In most cases, certain groups of allergens, as shared proteins, manifest a high
      cross-reactivity decreasing the diagnostics specificity. The issue of
      appropriateness and necessity of implementing the refined or artificial
      allergenic components is to be discussed. The experiment results confirmed the
      correctness of conclusions done and approaches chosen. The component-enabling
      diagnostics in the microarray format will make it possible to enhance the
      specificity and accessibility of analysis which will undoubtedly affect patients'
      quality of life.

PMID- 22416424
TI  - [The saliva cortisol level test using the automatic immunochemical analyzer Cobas
      e601 (Roche) to diagnose endogenous hypercorticalism in patients with obesity].
AB  - The saliva cortisol level test applies to diagnose endogenous hypercorticalism.
      However the methods of die format immunoassay traditionally used do not make it
      possible to get the study results on-the-fly. Also, reference interval and
      optimal takeoffs differ under implementing various techniques of cortisol tests.
      The purpose of actual study is to investigate the possibilities of
      electrochemiluminescent technique of testing free cortisol in saliva. The device
      Cobas e601 was applied to diagnose endogenous hypercorticalism in patients with
      obesity. The saliva samples were collected at 11 PM from 98 healthy volunteers
      and 123 patients with obesity (in 45 cases endogenous hypercorticalism was
      diagnosed). In total, 205 persons donated saliva at 11 PM two days running to
      evaluate the technique reproducibility. The samples of 197 individuals were
      frozen to implement the immune-enzyme assay. The minor test with dexamethasone
      was applied to patients with suspected endogenous hypercorticalism. The diagnosis
      of endogenous hypercorticalism was finally confirmed after the results of
      histological analysis of post-operative material or autopsy. Among healthy
      volunteers, the reference interval on indicators consisted 0.5-9.4 nMol/l. The
      correlation coefficient under free cortisol measuring at the same time two days
      running was -0.785. The optimal takeoff to diagnose endogenous hypercorticalism
      in patients with obesity consisted 9.4 nMol/l, sensitivity--84.4% (95% confidence
      band 71.2-92.2%), specificity--92.3% (95% confidence band 84.2-96.4%), predictive
      value of positive result--11.0 (95% confidence band 5.0-23.9), predictive value
      of negative result--0.17 (95% confidence band 0.08-0.33) and likelihood ratio for
      positive result--65.1 (95% confidence band 20.4-207.6). The two-fold cortisol
      test in saliva using immune-enzyme assay and minor test with dexamethasone with
      their diagnostic capabilities corresponded to one-fold saliva free cortisol test
      using electrochemiluminescent technique. The one-fold free cortisol test in
      saliva collected in 11 PM using the analyzer Cobas e601 for
      electrochemiluminescent immunoanalysis is a convenient and informative endogenous
      hypercorticalism screening technique in patients with obesity.

PMID- 22416425
TI  - [The optimization of techniques complex of serologic diagnostics of connective
      tissue systemic diseases].
AB  - The connective tissue systemic diseases originate from pathologic process
      following with antinuclear antibodies emergence. To detect these antibodies a
      significant number of diagnostic tests and techniques has been applied. Besides
      that, there is no conventional algorithm of antinuclear antibodies diagnostic. To
      detect antinuclear antibodies a two-fold diagnostic algorithm was applied In the
      capacity of screening techniques the indirect immunofluorescence technique was
      applied to the cells of line Hep-2 (antinuclear factor) and detection of
      antibodies to extractable nuclear antigen. The second stage of diagnostic
      included the detection of content of more specific antinuclear antibodies using
      the Lineblott method and the double-helical DNA antibodies. The blood serum from
      981 patients with suspected connective tissue systemic diseases, 115 patients
      with systemic lupus erythematous and 57 healthy individuals was analyzed. The
      levels of antinuclear factor, nuclear antigen antibodies and double-helical DNA
      antibodies were detected. The antinuclear factor was detected in 84% and 86% of
      cases, double-helical DNA antibodies in 55% and 39% of cases depending of
      reagents using in detecting these characteristics. Among healthy individuals,
      antinuclear factor was detected in 5% (1/20) of blood serum samples in titers
      less than 1:160. In the group of patients with suspected connective tissue
      systemic diseases, antinuclear factor was detected in 48% (474/981) of cases and
      extractable nuclear antigen in 20% (326/981) of cases. The Lineblott test was
      positive in 33% (326/981) of patients with suspected connective tissue systemic
      diseases. Among antinuclear factor positive patients nuclear antigen antibodies
      were detected in 36% (171/474) and the Lineblott test was positive in 63%
      (298/474) of cases. Among antinuclear factor negative patients but positive under
      anti-nuclear antigen identification, the Lineblott test was positive in 6%
      (28/507) of cases. The two-fold algorithm of nuclear antigen testing is an
      effective technique to be applied in the clinical diagnostic laboratory. The
      results of effectiveness of this algorithm demonstrated that this method can
      ensure 33% of cost savings of testing individuals with higher incidence of
      diseases.

PMID- 22416426
TI  - [The DNA-citometry of peripheral blood cells under particular pathologic
      conditions in children].
AB  - The article deals with the data concerning DNA-citometry of peripheral blood
      cells in healthy children and under particular pathologic conditions. The causes
      of shifts are discussed as their possible role in pathogenesis and clinical
      diagnostics of diseases as well.

PMID- 22416427
TI  - [The detection of minimal residual disease in patients with chronic B-cell
      lymphatic leukemia using patient-specified polymerase chain reaction].
AB  - The new effective protocols of treatment of chronic B-cell lymphatic leukemia,
      including purine analogs and monoclonal antibodies, provide robust remissions
      under this disease. Accordingly, the requirements to remission quality assessment
      are changed too. In particular the assessment of minimal residual disease is
      obligatory. To assess minimal residual disease in terms of quantity in case of
      chronic B-cell lymphatic leukemia the technique of polymerase chain reaction was
      applied in real time with patient-specific primers from the area of V-D-J
      combinations of genes of heavy chain of immunoglobulin. The study included
      samples from 60 patients suffering of chronic B-cell lymphatic leukemia. In 15 of
      them (25%), it was impossible to apply neither the sequence analysis of genes of
      heavy chain of immunoglobulin nor the fitting of patient-specific primer. The
      results of quantitative determination of minimal residual disease were obtained
      in 45 patients (55 tests). The minimal residual disease was detected in 30 of 55
      samples (54.5%) and was not detected in 25 of 55 samples (45.5%). At the same
      time, the quantitative determination of minimal residual disease was implemented
      in regard to the initial level of neoplastic cells. The method sensitivity
      qualified by serial dilutions, consisted 10(-5) or 1 neoplastic cell to 100 000
      normal cells. The comparative analysis was applied to the results of
      determination of minimal residual disease using two methods -polymerase chain
      reaction in real time using patient-specified primers and four-color flow
      cytofluometry. The determination of minimal residual disease with both methods
      was implemented in 37 patients (45 tests). The results of both methods matched in
      93.3% (42 tests out of 45) with maximal disparity of one degree. Then Spearman
      factor consisted 0.87 (p < 0.0001). In 3 out of 45 tests (6.7%) neoplastic cells
      were detected with only one method. In the first case, it was the method of four
      color flow cytofluometry and in other two cases it was polymerase chain reaction
      in real time. Therefore, the detection of minimal residual disease under chronic
      B-cell lymphatic leukemia using the method of polymerase chain reaction in real
      time is rather sensitive and specific and correlates with the results received
      with the method of four-color flow cytofluometry. The results are the same in the
      case of using anti-CD20 monoclonal antibodies under treatment.

PMID- 22416428
TI  - [The liquid cytology in clinical practice: a lecture].
AB  - The lecture covers one of the most perspective directions in clinical cytology.
      The emergence of liquid cytology is related to preparation of thin-layer
      specimens of organism liquids. Nowadays, the liquid cytology spreads more and
      more due to eephi application in different areas of cytological diagnostics,
      including screening of cervix uteri diseases, automatic screening, punctate
      tests, endoscopic and other materials. The lecture presents the basics of method,
      the characteristics of pre-analytic stage, the approaches to preparation of
      cytological specimens and cell blocks. The main possibilities, characteristics
      and perspectives of liquid cytology on the stage of rapid development of
      molecular genetic studies are discussed.

PMID- 22416429
TI  - [The atypical forms of mycoplasmas persisting in the organism of mycoplasma's
      infected persons].
AB  - The antigens, DNA and RNA of mycoplasmas are preset in the blood serum of persons
      infected with urogenital mycoplasmas. The planting of patients' tests of blood
      serum containing antigen M. hominis on the artificial growth mediums resulted in
      the growth of mini-colonies of mini-cells (20-50 nm). The colonies subcultured
      hardly but sometimes formed solid bacterial lawn though never acquired "fried
      egg" classical mycoplasma form. The proofs of identity of these colonies to M.
      hominis are presented. The mini-cells possessed infectiousness and ability to
      persist on a long-run in the internal organs of experimentally infected mice.
      Apparently, mini-cells are formed under impact of stress factors of the host
      immune defense and they are one of forms of mycoplasma's persistence in human
      organism.

PMID- 22416430
TI  - [The development of method of detection of human pathogenic orthopoxviruses on
      the basis of polymerase chain reaction in real time].
AB  - The set of specific oligonucleotide primers and hybridization testers with the
      support of TaqMan in real time is proposed to identify and differentiate such
      human pathogenic orthopoxviruses as smallpox virus, monkey smallpox virus, cowpox
      virus, variolovaccine. The analytical specificity of the set is determined upon
      the example of 20 strains of 6 types of human pathogenic orthopoxviruses and made
      up 100%. The sensibility is established using recombinant plasmids containing
      orthopoxviruses sequence. The minimal revealed amount of plasmid made up to 20
      copies for smallpox and monkey smallpox viruses, 10 copies for cowpox and 60
      copies for variolovaccine in reaction.

PMID- 22416431
TI  - [The laboratory diagnostic of pancreatitis of Yersinia etiology].
AB  - The effectiveness of diagnostic techniques detecting pancreatitis of Yersinia
      etiology is discussed. The agglutination reaction and immune-enzyme assay have
      been applied to detect the outer membrane proteins antibodies of various classes
      coded by plasmid of Yersinia virulence pYV. The polymerase chain reaction
      technique was applied to detect sites of chromosomal genes coding the factors of
      Yersinia virulence--superantigen toxin YPM Y. pseudotuberculosis and protein of
      adhesion/invasion of Ail Y. enterocolitica. The application of the complex of
      specific techniques of laboratory examination of patients with acute pancreatitis
      and chronic pancreatitis with exacerbations permitted to confirm the Yersinia
      etiology of disease in 23.7% of cases. Then serologic techniques are the most
      informative in laboratory diagnostics.

PMID- 22416432
TI  - [The evaluation of exocrinous function of pancreas in patients with chronic
      pancreatitis].
AB  - The article deals with studying the impact of low-intensity laser therapy on the
      exocrinous function of pancreas in patients with chronic pancreatitis in
      exacerbation stage. The sample included 49 patients aged from 36 to 69 years.
      They were allocated on the main (39 patients) and control (10 patients) groups.
      The patients from the main group received pharmaceutical treatment along with low
      intensity laser therapy. The patients from control group received only
      pharmaceutical treatment. The study demonstrated the positive impact of
      comprehensive therapy with low-intensity laser therapy added on the exocrinous
      function of pancreas in patients with chronic pancreatitis.

PMID- 22416433
TI  - [The laboratory diagnostics of Helicobacteriosis: express-test of antigen H.
      pylori in feces].
AB  - The article briefly discusses methods of diagnostic of the chelicobacterial
      infection. The information is presented concerning the implementation of
      immunochromatographic express-test in detecting the antigen H. pylori. The mode
      of test functioning is explained. The area of test application is discussed.

PMID- 22416434
TI  - [The metrology of medical devices for the diagnostic in vitro: the European
      approach].
AB  - In the European Union, the measurement devices are regulated by the Directive
      2004/22/EU establishing the mandatory requirements, rules of admittance and
      control/surveillance on the market. The medical laboratory analyzers don't come
      under the force of this Directive and are regulated by the Directive 98/72/EU in
      the same way as all medical devices for diagnostics in vitro. The new Russian
      Federal Law No102 "On the provision of the unification of measurements" came into
      force in 2009 is significantly harmonized with the similar international
      legislation and enable to eliminate the contradictions which for many years
      impeded the development of metrological support of clinical laboratory
      examinations.

PMID- 22416435
TI  - [On the examinations and measurement in laboratory medicine].
AB  - The issues of application of the Federal Law "On the provision of the unification
      of measurements" to the means of clinical laboratory analysis are discussed. The
      data of normative documents is presented to be used in the elaboration of agreed
      on documents of health authorities concerning metrology.

PMID- 22416436
TI  - [Is it possible to take blood for analysis in any time of day?].

PMID- 22416437
TI  - [Cardiorenal syndromes: pathogenetic, clinico-diagnostic, prognostic and
      therapeutic aspects].
AB  - Current information on cardiorenal and renocardial relations with
      clinicopathophysiological disorders in which primary impairment of the heart or
      kidneys leads to secondary functional and morphological abnormality in the other
      organ is analysed. Acute decompensation of cardiac failure is wide spread
      pathology which can be complicated by both acute and chronic lesion of the
      kidneys. Acute renal failure in cardiogenic shock in patients with ST elevation
      acute myocardial infarction deteriorates prognosis and raises lethality.
      Administration of radiopharmaceutical in patients with myocardial infarction and
      coronary heart disease with stents may induce nephropathy. Synergic affection of
      the heart and kidneys is observed in diabetes mellitus, systemic lupus
      erythematosus, amyloidosis, infectious endocarditis and some other diseases.

PMID- 22416438
TI  - [Structural and functional parameters of the vascular bed in premenopausal
      hypertensive women].
AB  - AIM: To study structural and functional characteristics of the vascular bed in
      premenopausal women with arterial hypertension (AH) and changes in hormone
      levels. MATERIAL AND METHODS: Duplex scanning of the common carotid arteries
      (CCA) was made in 180 females with premenopausal hypertension. RESULTS:
      Hypertensive women in premenopause with sexual hormones unbalance exhibited a
      wide CCA lumen in the absence of hemodynamically significant stenosis. This
      evidences for marked structural and functional changes of the vascular wall in
      the form of arteriosclerosis. Such patients' postocclusive reactive hyperemia
      test demonstrates a significant decline of vasomotor endothelial function, 43%
      cases show an inertial type of the vasomotor reaction reflecting an important
      role of hormonal unbalance in AH progression primarily due to increased stiffness
      of the vascular wall and endothelial dysfunction. CONCLUSION: Premenopausal women
      with hypertension and hormonal unbalance should be examined with consideration of
      the fact that impaired status of sexual hormones is an independent factor of risk
      of AH progression and they should be referred to a separate group of follow-up.
      Their treatment policy must be formed by both cardiologist and gynecological
      endocrinologist.

PMID- 22416439
TI  - [Efficacy of hypobaric hypoxia in the treatment of arterial hypertension in
      postmenopausal women].
AB  - AIM: To assess efficacy of adaptation to periodic hypobaric hypoxia (PHH) in the
      treatment of postmenopausal women with arterial hypertension (AH). MATERIAL AND
      METHODS: The method of adaptation to PHH in the pressure chamber Ural-1 (22 three
      hour daily sessions, pressure 460 mmHg) was used in 46 postmenopausal AH women
      (mean age 53.8 +/- 3.9 years). The method was assessed for effects on blood
      pressure (BP), symptoms of menopausal syndrome, body mass, levels of some
      hormones, lipid and carbohydrate metabolism. RESULTS: Adaptation to PHH reduced
      systolic pressure by 13.9%, diastolic one--by 8.2%, the levels of follicule
      stimulating and luteinising hormones by 26.8 and 21.5%, respectively, cholesterol
      -by 14.7, glucose--by 21.3, insulin--20.2%; estradiol and dehydroepiandrosteron
      sulphate concentrations rose by 19.3 and 15.2%, respectively. CONCLUSION:
      Adaptation to PHH produced an antihypertensive effect and a positive trend in
      clinicometabolic indices in AH women in postmenopause.

PMID- 22416440
TI  - [Efficacy of ivabradin in combined treatment of patients with postinfarction
      systolic chronic cardiac failure].
AB  - AIM: To study effects of ivabradin on clinicohemodynamic and prognostic
      parameters in patients after myocardial infarction (MI) with systolic chronic
      cardiac failure (SCCF). MATERIAL AND METHODS: A population-based randomized
      prospective trial enrolled 49 patients (40 males--81.6%, mean age 63.1 +/- 8.1
      years) with sinus rhythm and a longer than 3 month history of MI. The patients
      were randomized into 2 groups: 23 patients of group 1 received standard treatment
      plus ivabradin, 26 patients of group 2 received standard treatment alone. Follow
      up was 36.1 +/- 6.2 months. We analysed the trend in heart rate (HR), blood
      pressure (BP), parameters of echocardiography, ECG, levels of electrolytes,
      creatinin in blood plasma, frequency of hospitalizations, recurrent non-fatal MI
      and lethality (combined endpoint). RESULTS: In the end of the trial ivabradin
      significantly decreased HR from 71 to 64 b/m. Frequency of combined end point of
      efficacy was 30.4 and 50% in group 1 and 2, respectively. In group 1 primary end
      point in high baseline HR occurred more frequently than in HR < 70 b/m in 6 (50%)
      and 1 (9.1%) cases, respectively, but these differences were not significant (p =
      0.068). In group 2 the differences were significant--9 (90%) and 4 (25%) cases,
      respectively (p = 0.004). By none of the parameters of ECG, plasma electrolytes,
      creatinine level significant intergroup differences were found. CONCLUSION: In
      the same trend in BP and ECG, group 1 patients showed significant and more
      pronounced HR lowering than group 2 patients. Addition of ivabradin to standard
      treatment of SCCF after MI promoted less frequency of hospitalizations, recurrent
      non-fatal MI, fatal cardiovascular events. This effect was especially strong in
      high baseline HR.

PMID- 22416441
TI  - [Calcium channels blocker felodipin in the treatment of patients with arterial
      hypertension and chronic cardial failure with preserved cardiac output].
AB  - The article is devoted to issues of clinical diagnosis and treatment of patients
      with chronic cardiac failure and normal ejection fraction (CCF-NEF). Original
      clinical trials of felodipin efficacy designed to be maximally close to every-day
      clinical practice in Russia included hypertensive patients with CCF-NEF. The
      results of these trials bring about the conclusion that felodipin not only
      maintain blood pressure at the target level but also improves diastolic function
      of the myocardium.

PMID- 22416442
TI  - [Clinical functional assessment of electric cardiac instability in diastolic
      dysfunction of the left ventricle in patients with coronary heart disease].
AB  - AIM: To study parameters characterizing electric myocardial unstability in
      coronary heart disease (CHD) patients with different variants of diastolic
      dysfunction (DD) of the left ventricle (LV). MATERIAL AND METHODS: The study
      included 86 outpatients (26 females, 60 males, mean age 57.3 +/- 5.6 years) who
      had myocardial infarction (MI) more than 1 year before the trial with stable
      course of CHD during a previous month, LV ejection fraction more than 45% and
      with a stable sinus rhythm. Group 1 consisted of 36 patients with abnormal LV
      relaxation, group 2--of 28 patients with pseudo-normal LV DD, group 3--22
      patients with a restrictive type of LV DD. The following examinations were made:
      Holter ECG monitoring, echocardiography, signal-average ECG with isolation of
      late ventricular potentials (LVP), estimation of heart rate variability,
      ventricular repolarization (Q-T interval dispersion, corrected interval Q-T).
      RESULTS: The following variants of LV DD were detected: type 1--42%, type 2-
      32.5%, type 3--25.5%. LV DD progression was accompanied with enhancing vegetative
      imbalance and sympathetic activity: in the group with abnormal relaxation--in
      52.5% patients, in the group with a restrictive type--in 93.3%. CHD patients with
      restrictive DD had more frequent LVP (chi-square = 4.1; p < 0.05) and
      visualization of anomalous contractility zones (60%), ventricular extrasystole
      (VE) was registered in 100% cases (VE of grade IV-V in 43.3%), QT(c) and QT(d)
      were higher than threshold--450.2 +/- 5.4 and 71.2 +/- 6.5 ms. CONCLUSION:
      Because of multifactorial genesis of electric unstability, perfection of
      diagnosis and prognosis of risk in CHD patients with aggravation of LV DD demands
      a complex analysis of parameters respecting functional condition of the
      myocardium, relations between electric and structural-geometric remodeling of the
      heart.

PMID- 22416443
TI  - [Total body water and recurrent atrial fibrillation].
AB  - AIM: To specify the relationship between content of total body water and
      recurrent atrial fibrillation (AF) of non-valvular etiology. MATERIAL AND
      METHODS: Pharmacological amiodaron cardioversion followed by amiodaron supportive
      anti-arrhythmic therapy was made in 76 patients (47 males, 29 females, mean age
      58 +/- 8 years) with persistent AF of non-valvular etiology. Measurements were
      made of the height, body mass, arm circumference, thickness of the lipocutaneous
      fold above the biceps. Body mass index (BMI) and arm muscular circumference were
      estimated. Body composition was calculated according to Watson formula. RESULTS:
      Fifty three (70%) patients with recurrent AF had overweight or obesity. Body fat
      mass in patients with frequent (1 recurrence and more for 3 months) and rare AF
      recurrences did not significantly differ (24.4 +/- 10.6 and 30.0 +/- 13.8 kg,
      respectively; p = 0.064). Total body water was significantly less (36.8 +/- 5.2
      and 42.7 +/- 5.4 kg, respectively; p = 0.0009) in patients with frequent AF
      recurrences. Multifactor regression analysis showed that content of total body
      water, irrespective of gender and age, inversely correlates with an early AF
      recurrence (R2 = 0.24; beta = -0.49; p = 0.0003). CONCLUSION: Low content of body
      water is associated with a risk of early AF recurrence.

PMID- 22416444
TI  - [Thrombin-activated inhibitor of fibrinolysis and efficacy and safety of long
      term warfarin treatment in patients with venous thromboembolic complications].
AB  - AIM: To study effects of thrombin-activated fibrinolysis inhibitor (TAFI) on
      efficacy and safety of long-term anti-coagulant treatment in patients with venous
      thromboembolic complications (VTEC). MATERIAL AND METHODS: A total of 111
      patients with a history of an episode of deep vein thrombosis (DVT) and/or
      pulmonary artery thromboembolism (PATE) entered the study. All the patients
      received unfractionated or low-molecular heparin for at least 5 days than switch
      on warfarin (target values of INR 2.0-3.0). Baseline blood levels of TAFI were
      measured. The patients were followed up for 18 months. Recurrent (DVT/TAFI and
      hemorrhagic complications (HC) were endpoints. Also, frequency of complete lysis
      of deep vein thrombi was assessed after 12 months of treatment. RESULTS: A TAFI
      level varied from 50 to 217% (median 106%, interquartile rage 90-133%). TAFI
      concentration positively correlated with fibrinogen and thromb size. The patients
      were divided into two groups depending on TAFI content: group 1 patients had low
      TAFI (under 25th percentile; < 90%); patients of group 2 had high TAFI (above
      25th percentile; > 90%). Group 1 patients were characterized by less stable
      anticoagulation. This association did not depend on genetic characteristics which
      determine sensitivity to warfarin (CYP2C9 and VKORC1). Low TAFI was associated
      with reduced risk of DVT for 18 months and higher probability of complete lysis
      of the thrombi after 12 months of anticoagulant therapy compared to VTEC patients
      with high TAFI. No differences were found by TAFI level in patients with HC and
      without HC, but in HC patients low TAFI was associated with spontaneous
      hemorrhages and bleeding in therapeutic INR values. CONCLUSION: The results of
      this pilot study evidence that a TAFI level can be one of the factors influencing
      efficacy and safety of long-term anticoagulant therapy in patients with VTEC on
      warfarin treatment.

PMID- 22416445
TI  - [Pharmacokinetic and pharmacodynamic characteristics of antihypertensive drugs in
      the treatment of hypertensive patients with chronic diseases of the liver].
AB  - AIM: To determine optimal treatment of arterial hypertension (AH) in patients
      with hepatic cirrhosis (HC) basing on pharmacokinetic and pharmacodynamic
      characteristics of angiotensin-converting enzyme (ACE) inhibitors and beta
      adrenoblockers (BAB). MATERIAL AND METHODS: A total of 360 patients with AH of
      the second degree, steatosis and alcoholic HC of class A according to Child-Pue
      participated in the study. The control group consisted of 120 patients with
      peptic ulcer in remission and normal function of the liver. The patients'
      treatment with enalapril (pharmacologically inactive prodrug), lisinopril
      (biologically active substance), atenolol (hydrophilic drug) and metoprolol
      (lipophylic drug) was analysed. RESULTS: Lisinopril showed a better hypotensive
      effect than enalapril in AH patients with HC. BAB decreased blood pressure in all
      hypertensive patients. Atenolol and metoprolol effectively reduced blood pressure
      in 88.89% patients with AH and HC. Bradycardia episodes in atenolol treatment
      were observed in 14.4% patients while in metoprolol treatment--in 22.2% patients,
      this evidencing for pronounced shifts in pharmacokinetic parameters of metoprolol
      exposed to hepatic metabolism. CONCLUSION: Biological activity is an essential
      criterion of choice of ACE inhibitor in patients with hepatic pathology.
      Enalapril, for example, as a pharmacological inactive prodrug, is metabolized in
      the liver to acquire activity, whereas lisinopril has a direct biological
      activity and has, therefore, a stronger hypotensive action in AH patients with
      HC. BAB should be selected by the ability to effectively control blood pressure
      and heart rate without inducing bradycardia the appearance of which necessitates
      correction of dose regimen with reduction of day dose.

PMID- 22416446
TI  - [Postgastrectomy syndromes in therapeutic practice ].
AB  - AIM: To specify policy of nutritive support late after radical gastric resection.
      MATERIAL AND METHODS: Patients with postgastroresectional dystrophy were examined
      using standard techniques and estimation of intestinal electric activity
      (registration of body surface biopotentials on Conan-M myngograph). RESULTS:
      Frequency-amplitude parameters of the intestine serve the basis for choice of
      mixtures for enteral correction. Nutritive support provided for on demand
      pharmaconutrients--microbiotic correctors. CONCLUSION: Myography gives additional
      information for decisions on the policy of nutritive support.

PMID- 22416448
TI  - [Secondary autoimmune hemolytic anemia as a result of B19 parvovirus persistence
      in immunodeficient patients].
AB  - AIM: To ascertain informative value of immunological diagnosis of B19 parvovirus
      in combination with polymerase chain reaction (PCR); to analyse frequency of
      development of secondary autoimmune hemolytic anemia (AIHA) in immunodeficient
      patients as a result of virus persistence--persistent infection eliminated only
      by treatment causing suppression of erythropoiesis. MATERIAL AND METHODS: B19
      parvovirus detection was performed in blood serum of 207 subjects: 144 patients
      with anemia (Hb < 100 g/1) and 500 blood donors. DNA of parvovirus B19 was
      detected in the sera by PCR, antibodies to this virus--by enzyme immunoassay
      (EIA). IgG, IgM, IgA and components of compliment Clq, C3 on the surface of
      erythrocytes were detected by EIA in anemic patients. RESULTS: Parvovirus
      infection was registered in 30% patients, in 70% the infection was persistent.
      The latter were diagnosed to have secondary AIHA. CONCLUSION: Combined
      application of PCR and EIA extends potentialities of diagnosis of infection
      caused by B19 parvovirus. Persistence of the parvovirus provokes onset of
      symptomatic hemolytic anemia in immunodeficient patients.

PMID- 22416447
TI  - [Variability of intima-media thickness of the common carotid arteries in Moscow
      city population without clinical symptoms of atherosclerosis].
AB  - AIM: To determine borderline values of intima-media thickness (IMT) of the common
      carotid arteries (CCA) in Moscow citizens without clinical symptoms of
      atherosclerosis. MATERIAL AND METHODS: A total of 885 (277 males and 608 females)
      Moscow citizens aged 20-79 years free of clinical symptoms of atherosclerosis
      participated in population-based epidemiological trial. CCA IMT was measured at
      ultrasonic scanning of the carotid arteries in high-resolution regimen. RESULTS:
      The trial provided data on variability of CCA IMT borderline values in different
      age groups of adult Moscow metaethnic population without clinical symptoms of
      atherosclerosis with gender reference. Quartile distribution of CCA IMT values
      enabled primary evaluation of predisposition of the population studied to
      atherosclerosis. CONCLUSION: This pilot study is the first to give Russian data
      on variability of population borderline values of CCA IMT obtained in the study
      of a representative sample. Russian data give additional material to European
      geographic gradiet CCA IMT and allow more accurate ultrasonographic
      identification of predisposition to atherosclerosis in persons with silent
      disease.

PMID- 22416449
TI  - [Efficacy of rifaximine in small intestinal bacterial overgrowth syndrome in
      patients after cholecystectomy].
AB  - AIM: To define frequency of onset of small intestinal bacterial overgrowth
      syndrome (SIBOGS) in patients with postcholecystectomy syndrome (PCS); to
      substantiate necessity of microflora correction and assess efficacy of rifaximine
      in the doses 800 and 1200 mg/day. MATERIAL AND METHODS: A breath hydrogen test
      (BHT) was made in 82 PCS patients. Rifaximine was given to 40 SIBOGS patients: 20
      of them received the drug in a dose 800 mg/day and 20--in a dose 1200 mg/day for
      7 days. The efficacy was estimated by attenuation of the clinical symptoms and
      parameters of BHT. RESULTS: SIBOGS was detected in 73% of PCS patients. This was
      an indication for antibacterial treatment. Rifaximine in a dose 800 mg/day failed
      to attenuate pain and to eliminate dyspeptic syndromes in some patients, BHT in
      them was not normal. Administration of rifaximine in a dose 1200 mg/day
      normalized BHT in 90% patients and eliminated clinical symptoms in most of the
      patients. CONCLUSION: Rifaximine in a dose 1200 mg/day vs 800 mg/day in PCS
      patients with SIBOGS is more effective as it eliminates clinical symptoms and
      normalizes BHT.

PMID- 22416450
TI  - [Treatment of diabetes mellitus in dialysis patients].
AB  - Diabetes mellitus is a key cause of chronic kidney disease (CKD) in developed
      contries. Disorders of glucose metabolism regulation in CKD are explained by
      insulin resistance, decreased insulin clearance, weak hormonal response to
      hypoglycemia. These disturbances appear in inhibition of glomerular filtration
      rate under 60 ml/min. Hemodialysis treatment raises the risk of hypoglycemic
      conditions due to glucose elimination from blood circulation during the sessions
      and improvement of sensitivity to insulin. Use of glucose-containing solutions
      for dialysis, step-by-step achievement of normoglycemia, monitoring of blood
      glucose during dialysis sessions are recommended for reducing the risk of
      hypoglycemic conditions in DM patients on dialysis. Insulin is the most common
      preparation in the treatment with use of hemodialysis in diabetics.
      Tiasolidindions (pioglitason, rosiglitason) and analogues of dipeptidilpeptidase
      of type IV (sitagliptin, saxagliptin) can be administered in type 2 diabetics
      without insulin insufficiency. As solutions for peritoneal dialysis contain
      glucose, such dialysis may entail such metabolic complications as fat
      accumulation, metabolic syndrome. Intraperitoneal introduction of insulin allows
      avoiding hyperinsulinemia and in some cases to decrease the risk of hypoglycemia.
      Side effects of intraperitoneal insulin administration are significant absorption
      of insulin on the surface of the systems for intraperitoneal dialysis, higher
      rate of peritonitis, subcapsular hepatic steatosis. In the absence of controlled
      studies the mode of insulin administration in patients on peritoneal dialysis
      should be chosen individually basing on potential risk and benefit for the
      patient and experience of the dialysis center. It should be remembered that
      adequate sugar-reducing treatment is necessary for prevention of complications
      and prolongation of survival of diabetics on dialysis.

PMID- 22416451
TI  - [From classification medicine to clinical medicine (the end of the XVIII century 
      1870s). Communication 4. Health care in the end of the XVIII century--first half
      of the XIX century].
AB  - This communication deals with problems in health care which existed in the end of
      the XVIII century--first half of the XIX century.

PMID- 22416452
TI  - [SNP-specific mismatched PCR for embryonic DNA detection using blood from
      pregnant mothers].
AB  - BACKGROUND: Although prenatal diagnoses are performed using amniotic fluid cells,
      chorionic villus, or cord blood, these methods are hazardous for pregnant woman
      and the fetus. To determine a procedure for safe prenatal diagnosis, we have
      developed a sensitive method to analyze SNPs and we evaluated the possibility to
      detect fetal DNA in the maternal blood. METHODS: GeneScan analysis was performed
      by using mismatched specific primers for 5 SNP types and fluorescein amidite
      (FAM) labeled primers, and Real-time PCR analysis was also performed by using
      mismatched specific primers for the same SNP type and probes labeled with FAM and
      black hole quencher. DNA from healthy volunteers' blood was used for a primary
      examination to establish procedures, and DNA from 200 microl of blood from
      pregnant women, their partners and children were used for detection of fetal DNA
      and/or typing and selection of SNPs. RESULTS: To evaluate the sensitivity of this
      method, mixing tests of DNA containing a SNP nucleotide and its counterpart
      indicated the sensitivities were 10(-1)-10(-3) for GeneScan analysis and 10(-1)
      10(-4) for Real-time PCR analysis. Fetal DNA (rs3769393-A and G) was detected in
      blood from pregnant women (GG-type mother: 2 out of 2, AA-type mother: 1 out of
      2) only at 18 and/or 28 gestation weeks by Real-time PCR analysis. However, 4
      SNPs measured by Real-time PCR analysis and 5 SNPs examined by GeneScan analysis
      were not detected in all women in different gestation periods. CONCLUSIONS: We
      established a SNP detection method using GeneScan and Real-time PCR analysis. The
      latter detected fetal DNA in 200 microl of blood in only some pregnant women. We
      speculate that using a large amount of DNA from nucleated erythrocytes in 20 ml
      of blood will improve the detection rate of fetal DNA.

PMID- 22416453
TI  - [Relativity in multiple myeloma and KL-6].
AB  - KL-6 is a high-molecular-weight mucinous glycoprotein discovered as a pulmonary
      adenocaricinoma related antigen. Its levels are used as a biomarker of lung
      injury in interstitial pneumonia. We here report a case of multiple myeloma with
      Bence-Jones lambda type whose serum KL-6 level was revealed high at a
      concentration of 19,400 U/ml. Next, we analyzed the blood test profiles and the
      concentrations of KL-6 in 20 patients with multiple myeloma. CD19/CD56 double
      negative fraction on myeloma cells with high expression of CD38 was found in all
      5 patients with multiple myeloma having elevated KL-6 level. Patients with
      interstitial pneumonia show high level of KL-6. We, therefore, need to
      differentiate the interstitial pneumonia and the above-mentioned multiple myeloma
      when serum KL-6 level is high.

PMID- 22416454
TI  - [Case with intrauterine fetus death: interphase fluorescence in situ
      hybridization using buccal cells is useful for examining chromosomal
      abnormalities when placental villus not available].
AB  - The proband was a male fetus who died at 18 weeks of gestation. The fetus had
      growth retardation, hydrocephalus, exophthalmos, and micrognathia. The placental
      villus was not available. We performed interphase fluorescence in situ
      hybridization (FISH) using buccal cells of the fetus. The FISH using centromere
      specific probes for chromosome 7, 8 and 18, and RB1 gene (13q14)-specific probe
      showed three signals for each chromosome. The sex chromosome composition was XXY
      by FISH using centromere-specific probes for X and Y chromosomes. Thus, the fetus
      was diagnosed with triploidy syndrome. This report suggested that interphase FISH
      using buccal cells is useful for examining chromosomal abnormalities in
      intrauterine fetal death when placental villus is not available.

PMID- 22416455
TI  - [Rheumatic diseases and research on laboratory medicine: new applications of old
      knowledge].
AB  - Although the etiology of rheumatic diseases has not been elucidated, it seems to
      be involved in excessive autoimmune responses. In 1976, we began to research
      rheumatic diseases, especially rheumatoid arthritis. Anti-human immunoglobulin
      allotype antibodies in Japanese sera were collected from blood donors or patients
      by hemagglutination and the hemagglutination inhibition method using anti-D
      sensitized erythrocytes. Many rheumatoid factors without any specificity to IgG
      allotypes (Gm allotypes) were detected in patient sera. On the other hand, so
      called anti-antibodies, Andresen type but not Milgrom type, were mainly detected
      in blood donors. Thirty-nine sera possessing anti-Gm and anti-Km antibody
      specificities were finally obtained by screening about 80,000 Japanese. The
      antibody to G1m (f) was most frequently detected, but the antibody to G1m (z),
      which is an allele of G1m (f), was not obtained. Quantitative evaluation of
      rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPA) was
      adopted in the 2010 ACR/EULAR classification criteria for rheumatoid arthritis;
      however, quality management of RF has been incompletely implemented in Japan. We
      therefore mounted an effort to standardize the cutoff value. We found marked
      hyperferritinemia in patients with active adult Still's disease in 1987.
      Additionally, ratios of glycosylated ferritin in the patients were extremely
      reduced, even if they came into the inactive phase. This depressive production of
      glycosylated ferritin might be a marked characteristic of this disease. Finally,
      the development of musculoskeletal ultrasonography in rheumatic diseases is
      introduced.

PMID- 22416456
TI  - [Establishment of the rapid, hypersensitive testing systems for sepsis/SIRS].
AB  - We developed a new infectious disease diagnostic system in order to raise the
      lifesaving rate in systemic inflammatory reactive syndrome, SIRS. Using eukaryote
      derived thermostable DNA polymerase, the sensitive and reliable detection of
      bacteria becomes feasible for large fields, thereby making the development of a
      wide range of powerful applications possible. Further, we have established a
      novel measurement system for NF-kappaB activity using fluorescence correlation
      spectroscopy(FCS) because the elevation of NF-kappaB activity reflects acute
      inflammation. NF-kappaB activity measurement in patients with SIRS may provide a
      useful inflammatory marker.

PMID- 22416457
TI  - [Recent development in platelet functions: roles beyond thrombosis].
AB  - In addition to their roles in thrombosis and hemostasis, there is an increasing
      body of evidence to suggest that platelets have diverse functions in various
      biological reactions. Of these, synthesis of specific proteins in a timely
      manner, involvement in inflammation, roles in anti-bacteria and anti-parasite
      protection, and supportive roles in liver regeneration have attracted the
      attention of a number of scientists. We have recently found a novel platelet
      activating receptor, CLEC-2, which reacts with a snake venom, Rhodocytin. CLEC-2
      has an intracellular signal transduction pathway quite similar to that of GOVI,
      except for its hemi-Y-xx-L motif. The endogenous ligand for CLEC-2 was identified
      by us as podoplanin, which is present in renal podocytes, lung alveolar
      macrophages, and lymphatic endothelial cells, and some types of malignant tumors.
      We found that CLEC-2/podoplanin interaction plays an important role in the
      metastasis of tumor cells with podoplanin expression. We have also found that
      hemophilic interaction between CLEC-2 molecules contributes to thrombus formation
      in vivo. CLEC-2 interaction with podoplan expressed on lymphatic endothelial
      cells appears to play an important role in the separation between veins and
      lymphatic vessels during the stage of fetal development.

PMID- 22416458
TI  - [Systematic approaches to hematological diseases based on the partnership between
      clinical divisions and laboratories--summary].
AB  - The prompt and appropriate communications between clinical divisions and clinical
      laboratories are essential particularly to the diagnosis and treatment of
      hematological disorders. In this symposium, four speakers presented and discussed
      the issues as follows: importance of molecular analyses on clinical hematology;
      practical aspects and utility of specialized works by a laboratory hematologist;
      an application of the integrated laboratory hematology system for better
      contribution to clinics; and finally the reconstruction of the partnership
      between clinical divisions and laboratories just after the terrible earthquake
      which took place in the northeast Japan area in March, 2011. In particular, the
      recovery process of the hospital after the unfortunate earthquake let us realize
      the mutual cooperation of the laboratories and the clinics exactly.

PMID- 22416459
TI  - Assessment of work-related muscle strain by using surface EMG during test
      contractions interposed between work periods of simulateted mushroom picking.
AB  - Surface electromyograms(EMG) during test contractions (TCs) were studied to
      assess the muscle strain in simulated mushroom picking. Additionally, the
      duration of the TC for the effective assessment was investigated. Nine female
      subjects performed standardized shoulder abduction and a stooped posture for one
      minute as TCs. Each experiment consisted of a 60-min rest, three work periods (W1
      W3), a 30-min rest, and two work periods (W4 and W5) separated by a 30-min rest
      period. The duration of each work period was about 20 min. A total of 18 TCs was
      performed between the work periods and every 10 minutes in the rest periods. EMGs
      were recorded from the trapezius, infraspinatus, deltoid, and erector spinae
      muscles. The amplitude of EMG (AEMG) and mean power frequency (MPF) of EMG were
      calculated. Each TC was divided equally into three parts. Ratings of perceived
      exertion (RPE) in the neck, shoulder and low-back were reported during TCs. The
      work increased RPE of all the parts. AEMG and RPE were increased and MPF was
      decreased by W1, W2 and W3 in the neck and shoulder muscles. MPF of the erector
      spinae was increased by the work. The results were not affected by the duration
      of TCs and the parts during the TCs. AEMG and MPF fluctuated before W1 although
      the changes of RPE were small. Averaging several TCs was recommended to get
      stable results from TCs. EMG changes and appropriate TC conditions were discussed
      in relation to the adaptation in fatiguing contractions.

PMID- 22416460
TI  - Influence of high ambient temperatures on the physiological responses and body
      sway in healthy young adults after quickly standing.
AB  - This study was aimed to compare the variations in cerebral oxygenation, blood
      pressure and center-of-foot pressure after standing from sitting and supine
      positions at normal (22 degrees C) and high (32 degrees C) room temperatures.
      Thirty young adults stood up from a resting posture (sitting or supine position)
      and kept the static standing posture for 90 sec. Meanwhile, their center-of-foot
      pressure (COP), blood pressure, and cerebral oxygenation kinetics were measured
      in continuity. The change of the frequency domain low-to-high frequency (LF/HF)
      ratio of the R-R interval before and after standing from a supine position was
      significantly higher than that from a sitting position under both temperature
      conditions. Blood pressure as well as total and oxygenated hemoglobin levels
      decreased immediately after standing up and the ratio of blood pressure change
      when moving from a supine position to standing at high room temperature was the
      largest as compared with the other conditions. Total hemoglobin (Hb) volume was
      found to temporarily decrease after standing and required 22-24 sec to recover
      when the subject started from the sitting position and 33-36 sec when the subject
      started from the supine position. Cerebral oxygenation kinetics tended to be
      larger under high, rather than normal, temperature conditions. All COP parameters
      after standing were significantly larger in the high temperature condition than
      in the normal temperature condition. Body sway after standing was larger in the
      high temperature condition than in the normal temperature condition and after
      standing from a supine position than from a sitting position. In conclusion,
      cerebral oxygenation kinetics and blood pressure measured after the subject moved
      to the standing position changed dramatically under high temperature conditions,
      and variations in this parameter may influence body sway.

PMID- 22416461
TI  - Anthropometric characteristics of Indian cycle rickshaw pullers.
AB  - In India, about 0.86 million people is engaged in pulling cycle rickshaws as
      occupation. There is no anthropometric data of cycle rickshaw pullers although
      data is available for Indian population. The objective of the study was to
      collect anthropometric data of the cycle rickshaw pullers so that these could be
      utilized for redesigning a cycle rickshaw. Anthropometric data for 34 body
      measurements were recorded from 880 rickshaw pullers (age 18 to 66 years) of four
      different places in India. The mean values of different standing heights,
      different lengths and breadths of cycle rickshaw pullers were significantly lower
      compared with Indian population. However, there was no significant difference in
      erect sitting height. The outcome of the research project is beneficial for the
      manufacturers of cycle rickshaws and similar products well as users of such
      products, including rickshaw pullers. The manufacturers would be able to use the
      data for fabricating newer models of cycle rickshaws which would be more
      compatible for rickshaw pullers as well as passengers.

PMID- 22416462
TI  - Critical period for menarche derived by the wavelet interpolation method from
      changes in BMI with age in South Korean girls.
AB  - Recently, few studies regarding the changes in BMI with age have been reported.
      In the present study, the wavelet interpolation method (WIM) was applied to the
      changes in BMI with age from the first grade of elementary school until the
      second year of high school in Korean girls, and the relationship between age at
      the maximum peak velocity (MPV) of BMI and age at menarche was confirmed by
      determining the age at MPV of BMI. Age at menarche and activity status were
      obtained from questionnaires given to 263 second grade high school girls in the
      Pusan area of South Korea. Moreover, longitudinal growth data on height and
      weight from the first grade of elementary school until the second year of high
      school (from 1997 to 2008) were obtained from health examination records. BMI was
      calculated from height and weight values from the first grade of elementary
      school until the second year of high school, and wavelet interpolation was
      applied to the distances of BMI in each grade. The change curve of BMI with age
      was determined by wavelet interpolation, and the age at MPV of BMI was determined
      from the changes in the velocity curve with age as the differentiation curve. Age
      at MPV of BMI was found to be 12.76 +/- 1.6 years, and age at menarche to be
      12.34 +/- 1.1 years. The interval in age at the two times was -0.42 +/- 1.6
      years, and a significant difference was seen between age at menarche and age at
      MPV of BMI. The reason that the age at menarche was a little earlier than the age
      at MPV of BMI is hypothesized to be abnormal melatonin levels influenced by lack
      of sleep in Korean school girls. However, it is proposed that the age at MPV of
      BMI is valid as the critical period for the age at menarche.

PMID- 22416463
TI  - The ergonomic evaluation of work-related musculoskeletal disorders among
      construction labourers working in unorganized sectors in West Bengal, India.
AB  - The present study aimed at ergonomic evaluation of the prevalence of work-related
      musculoskeletal disorders among construction labourers working in unorganized
      sectors in West Bengal, India. A modified Nordic questionnaire was applied to one
      hundred forty male and ninety female construction labourers to acquire
      information about musculoskeletal symptoms like pain in different body parts.
      Work-rest schedules of the labourers in different work activities were studied.
      Working postures were analyzed by means of the Rapid Entire Body Assessment
      (REBA) tool. Body part discomfort (BPD) scale was used to assess the intensity of
      feeling of discomforts in the different body parts. It was revealed that the
      labourers performed repetitive, stressful work for a long period of time in a
      single work-rest cycle and the load lifted and carried by them were more than the
      NIOSH recommended weight limit. The analyses of working postures revealed that
      most of their working postures were unsafe and ranked under REBA action level 3
      and 4. The results obtained by applying the Nordic questionnaire and BPD scale
      revealed that the prevalence of pain in various regions of the body, especially
      low-back pain, was alarmingly high in both male and female labourers. Training
      for safe lifting of materials, proper work-rest schedule, modifications of some
      working procedures and the use of ergonomically designed equipment may certainly
      reduce the work-related musculoskeletal disorders and improve the health status
      of construction labourers working in unorganized sectors.

PMID- 22416464
TI  - Handgrip prediction models for children, adults and the elderly.
AB  - This paper describes the development of a set of multiple linear regression
      equations for predicting maximal voluntary static handgrip strength of males and
      females, 5-89 years of age, in each hand. Equations are presented for predicting
      handgrip strength of the left and right hands from: (i) overall body descriptive
      variables alone--age, sex, body weight and stature, (ii) overall descriptive
      variables plus pinch strength variables, and (iii) pinch strength variables
      alone. A data set on 182 persons living in the United States was used for this
      study. Two-thirds of the observations were used to develop the models and the
      rest for validating them. Models were found with 3-5 variables, R2 ranging from
      0.80-0.87, and root mean square error from 4.7-5.8 kg. Among the most common
      predictor variables that appeared in the models were: stature, age, sex, and the
      stronger pinches (chuck, lateral and pulp-2). Model validation indicated a
      greater tendency to over-predict left hand strength but no directional tendency
      for right hand strength. Also prediction accuracy (mean absolute percentage
      error) ranged from 14.9-21.0%, with about equal magnitudes in the two hands. The
      regression model coefficients were refined by recombining the data set of 182
      observations and performing the appropriate regressions analysis.

PMID- 22416465
TI  - Extracting and understanding the relationship between components of the capacity
      in elderly people in terms of electrical device comprehension.
AB  - The purpose of this study is to extract components of the capacity which elderly
      people have in comprehending electrical devices and determine its relationship
      with the components. Initially, we proposed a hypothesis through examining
      previous studies. The hypothesis states that the capacity which elderly people
      have mainly consists of four components, i.e., motivation, working memory,
      logical thinking and experience with personal computers (PC) or mobile phones.
      Then, some tests were conducted to examine the hypothesis. In this research,
      elderly people were interviewed about their impressions and experience with
      electrical devices. Moreover, three tests were conducted including, card sorting,
      tasks using digital video cameras and a test to measure working memory. As
      analysis methods, the Quantification 1 was used to see which component was
      important. In addition, Boolean algebra was conducted to simplify the components
      and understand some relationships. As a result, a relationship with the
      components in electrical devices was revealed. Furthermore, the use of Boolean
      algebra and the Quantification 1 suggested that the experience with PCs or mobile
      phones was the most important component for elderly people.

PMID- 22416466
TI  - The preferable keypad layout for ease of pressing small cell phone keys with the
      thumb.
AB  - The present study investigated the effect of keypad layout on the ease of
      operating small cell phones with the thumb in one-handed operations by young and
      elderly male and female participants. Eighteen young participants (9 males and 9
      females) and 12 elderly participants (6 males and 6 females) operated 9 different
      keypads modeled after commercially available cordless handsets. Keypads designed
      by using the L9 orthogonal array differed in vertical pitch (V-Pitch: 7, 8, 9 mm)
      between keys, horizontal pitch (H-Pitch: 10, 11, 12 mm) between keys, the margin
      below the bottom row of keys (B-Margin: 5, 13, 21 mm), and phone body width (P
      Width: 38, 41, 44 mm). Results concerning subjective overall usability showed the
      lowest scores for a V-Pitch of 7 mm and a B-Margin of 5 mm in most groups.
      However, for the female participants, with shorter thumbs, the increase in V
      pitch did not improve operability. In the elderly participants, miskeying
      frequently occurred at dial keys of specific numbers. These findings suggest that
      the preferable keypad layout differs between different age groups and between
      male and female participants.

PMID- 22416467
TI  - [Mechanisms for the regulation of the plasma membrane curvature in endocytosis].

PMID- 22416468
TI  - [Regulation of osteogenesis and chondrogenesis by unfolded protein respone].

PMID- 22416470
TI  - [Molecular mechanisms of invadopodium formation by cancer cells].

PMID- 22416469
TI  - [BAR domain superfamily proteins bind to the cellular membrane of various
      curvatures].

PMID- 22416471
TI  - [Protein kinase NLK, that fine-tunes the activity of multiple intracellular
      signaling pathways].

PMID- 22416472
TI  - [Characteristics of tumor endothelial cells].

PMID- 22416473
TI  - [Visualizing spatiotemporal dynamics of multicellular cell-cycle progression].

PMID- 22416474
TI  - [New horizons in biological research developed by next-generation proteomics: say
      good-bye to Western blotting].

PMID- 22416475
TI  - Inflammatory markers in active pulmonary tuberculosis: association with Th1/Th2
      and Tc1/Tc2 balance.
AB  - OBJECTIVE: Few inflammatory markers closely reflect the activity of tuberculosis
      and only a few surrogate markers are available. The purpose of this study was to
      clarify the usefulness of measuring the erythrocyte sedimentation rate (ESR), C
      reactive protein (CRP), and serum amyloid A (SAA), and the association between
      these markers and T-cell profiles. METHODS: One hundred one patients with active
      pulmonary tuberculosis were enrolled in this study. The associations between ESR,
      CRP, and SAA values on admission and microbiological and radiological findings
      and T-cell profiles were assessed. Th1/Th2 and Tc1/Tc2 were determined by
      analyzing intracellular cytokine staining for IFN-gamma and IL-4 in blood CD4+
      and CD8+ T cells using flow cytometry after stimulation with PMA and ionomycin.
      RESULTS: There were significant correlations between ESR, CRP, and SAA, of which
      the correlation between CRP and SAA was strong (r = 0.88). CRP values
      significantly correlated with the sputum smear scale and the extent of lesions,
      and were higher in bilateral lesions. SAA values correlated with the sputum smear
      scale, whereas all markers were higher in patients with pleural effusion. Both
      CRP and SAA levels negatively correlated with the ratio of Th1/Th2. In contrast,
      ESR negatively correlated with the ratio of Tc1/Tc2. CONCLUSION: CRP reflected
      the disease severity before treatment. CRP and SAA values were associated with
      helper T-cell proportions whereas ESR was associated with cytotoxic T-cell
      proportions, both being type 2 predominant.

PMID- 22416476
TI  - A case of pulmonary tuberculosis with false negative QuantiFERON TB-2G Test.
AB  - A 57-year-old man was admitted to our hospital with a high fever and productive
      cough. He had a previous history of total gastrectomy and splenectomy at the age
      of 45 years due to gastric cancer. He also showed severe macrocytic anemia with
      low vitamin B12, and an infiltrative shadow was found in the right lung on an X
      ray. Sputum examination on admission revealed no significant pathogenic bacteria,
      and an acid-fast stain and a M. tuberculosis PCR test were negative. QuantiFERON
      TB-2G Test (QFT) was negative on admission. Because pneumococcal antigen in the
      urine was positive, we initially diagnosed pneumococcal pneumonia and treatment
      with antibiotics was started. However, symptoms were not resolved with several
      antibiotics, finally, a thoracoscopic lung biopsy under general anesthesia was
      performed for a definitive diagnosis. The biopsy showed epithelioid cell
      granuloma in the alveolar spaces, and the 8 weeks culture of sputum taken on
      admission revealed M. tuberculosis. Finally, a pulmonary tuberculosis was
      diagnosed and treatment with four drugs of HERZ was begun. We have encountered a
      case of pulmonary tuberculosis combined with a lobar pneumococcal pneumonia, and
      negative for QFT. In general, splenectomy is known as a risk factor of
      pneumococcal infection. And vitamin B12 deficiency due to gastrectomy is one of
      the risk factors for cellular immunity impairment and was possibly to the false
      negative QFT and development of TB.

PMID- 22416477
TI  - Computerized surveillance system of tuberculosis in Japan: its evolution,
      achievement and challenges.
AB  - The nationwide computerized tuberculosis (TB) surveillance system was revised in
      2007. It was developed to be user-friendly and to allow the evaluation of current
      TB problems and control issues in Japan. All public health centers in Japan (518
      as of April 2007) have system terminals connected to a central computer, and the
      data entered at these terminals are sent to the online central computer excluding
      personal identification data. All the figures and tables in this paper were
      created using the annual report database which are compiled from this system. The
      revision in 2007 added many new functions to the system, such as a function for
      automatically sending data upon transfer. The monitoring information for
      assisting case management of TB patients by the DOTS was also enhanced. The
      algorithm for classifying treatment outcomes automatically based on data entered
      regarding cancellations from registration, bacteriological results and drug usage
      each month was revised. The proportion of "Failed" and "Defaulted" combined was
      4.6% among new sputum smear positive pulmonary TB patients newly registered in
      2009, while "Died" accounted for as high as 19.3%, due largely to a high
      percentage of the elderly. A new system for contact examination management is
      provided as a subsystem. Feedback of data analyses has been strengthened by
      various methods. This TB surveillance system is indispensable for implementing
      the evidence-based TB control program in Japan. An important role of the Research
      Institute of Tuberculosis is to support the planning and execution of TB control
      with provision of useful epidemiological information from the system.

PMID- 22416478
TI  - [Clinical consideration of coagulase negative Staphylococci isolated in blood
      culture].
AB  - Despite blood culture's usefulness in antimicrobial therapy, fewer blood cultures
      and the infrequency of more than 1 set in cultures appear to be problems in
      Japan. Since June 2007 infection control team (ICT) recommended more than 1 set
      in blood sampling and intervention in positive blood culture, coagulase negative
      Staphylococci (CNS) has frequently been isolated from blood culture and its
      clinical significance is often difficult to judge. To determine the effect of ICT
      intervention, we evaluated the number of blood culture specimens, the frequency
      of more than 1 set in all blood culture specimens, and decision-making on
      antimicrobial treatment for CNS isolated retrospectively from blood. The study
      was divided into term I in August 2007 to July 2008, term II in August 2008 to
      July 2009, and term III in August 2009 to February 2010. We also analyzed how
      physicians treated infection or its suspicion after CNS and its drug
      susceptibility. The monthly number of blood culture specimens increased from 40.3
      to 51.6 between terms I and III. The frequency of more than 1 set in a single
      blood culture session rose significantly from 67% to 89% between these terms (p <
      0.001). The number of indeterminate also dropped cases significantly during these
      2 terms from 27% to 6% (p = 0.017). Infection or suspected infection cases--45 of
      49--had central vein catheter implantation. Inappropriate treatment by physicians
      in these cases also dropped significantly from 85% (11/13) to 45% (5/11) (p =
      0.043) during the same 2 terms. ICT Intervention may thus increase the number of
      blood culture specimens, enable more than 1 set in blood sampling, make it easier
      to judge the presence of infection, and increase appropriate treatment by
      physicians. We thus believe that the quality of antimicrobial treatment could be
      improved through education such as ICT action.

PMID- 22416479
TI  - [Seasonal changes of invasive pneumococcal disease in children and association
      with day care attendance].
AB  - To determine seasonal changes in the incidence of invasive pneumococcal disease
      (IPD) in children, we retrospectively analyzed 69 children with 72 episodes of
      IPD, admitted to a regional center in Kobe, Japan, between July 1994 and June
      2011. IPD episodes involved occult bacteremia (n = 48), pneumonia (n = 10),
      meningitis (n = 10), periorbital cellulitis (n = 3), and mastoiditis (n = 1),
      including 3 cases of two IPD recurrences. We analyzed 5 IPD-associated factors
      previously documented in Europe and North Amrica with inconsistent results--1)
      age at onset, 2) sibling number, 3) preschool sibling number, 4) subjects' day
      care attendance, and 5) siblings' day care attendance. We collected information
      on these factors by reviewing medical charts or contacting subjects' parents or
      guardians by telephone. IPD peaked bimodally in April and May (n = 21) and in
      November and December (n = 20), decreasing prominently between July and September
      (n = 8). Subjects with IPD attending day care formed a significantly higher
      propotion during April and May than did those developing IPD during other months:
      12/21 [57.1%] vs. 12/51 [23.5%], odds ratio 4.3, 95% confidence interval, 1.5
      12.8; p = 0.006. Combined day care attendance among subjects with IPD and/or
      their siblings also differed significantly between these two groups: 17/21
      [80.9%] vs. 27/51 [52.9%], odds ratio 3.8, 95% confidence interval, 1.1-12.8; p =
      0.027. Not significant differences were seen in age at onset, sibling number, or
      preschool sibling number. In contrast, however children with IPD onset during
      November and December showed no significant difference in association with any of
      the 5 factors, compared to children with IPD onset in other months. Our findings
      showed a bimodal peak in IPD in children, the first and highest of which occurred
      in April and May and was significantly associated with day care attendance by
      those with IPD and/or their siblings. This first peak may, however, be related to
      circumstances in Japan, where preschool children usually enter day care center or
      kindergarten in April.

PMID- 22416480
TI  - [Analysis of inpatients with pneumonia due to influenza (H1N1) 2009--clinical
      aspects based on the presence or absence of respiratory complications].
AB  - We retrospectively analyzed the clinical aspects of inpatients with pneumonia
      caused by influenza (H1N1) 2009 after classifying them into two groups based on
      the presence or absence of respiratory complications. The study population--121
      (5.6%) of 1,777 subjects diagnosed with influenza (H1N1) 2009 using a rapid
      influenza diagnostic kit or real-time reverse-transcription PCR-were hospitalized
      from August 2009 to May 2010 as detailed from admission to discharge in hospital
      medical charts. Of these, 72 had respiratory symptoms and most -56, or 3.2%, of
      the total-were diagnosed with pneumonia in chest radiography. The mean age of
      those with pneumonia was 6.9 years, 35.7% had a history of bronchial asthma and
      80.4% were admitted within three days of onset. Some 75% of those with pneumonia,
      or 42, had respiratory distress (SpO2 < or = 93%) requiring supplementary oxygen.
      Significant lymphopenia and neutrophil increase were observed in blood tests of
      those admitted within three days of onset. Almost all were given an antiviral
      agent for 5 days. Among pneumonia cases, 14 (25%) also had severe respiratory
      complications such as pneumomediastinum and atelectasis, designated the
      complications group. They also had significantly lower oxygen saturation and
      significantly more elevated non-specific IgE on admission than those in the non
      complications group (n = 42). Those with complications were hospitalized for
      significantly longer, and were administered isopretenol. All inpatients with
      influenza (H1N1) 2009 were discharged as healthy. Based on our retrospectively
      analyzed results in those with influenza (H1N1) 2009 pneumonia, we concluded that
      the following medical circumstances covered by the Japanese insurance system help
      lead to good outcomes: i) visiting the hospital soon after onset, ii) being
      diagnosed early using a rapid identification kit, iii) under-going systemic whole
      body management, and iv) being administered antiviral and antibacterial agents.

PMID- 22416481
TI  - [Fungemia caused by Scedosporium prolificans in myelodysplastic syndrome].
AB  - We report a case of fungemia caused by Scedosporium prolificans, an emerging
      pathogen. An 83-year-old man with myelodysplastic syndrome (MDS) and
      agranulocytosis was admitted for pneumonia in January 2009. He was treated with
      meropenem, minocycline, and gamma-globulin for pneumonia and G-CSF and platelet
      transfusion for MDS. Although he recovered from pneumonia as neutrophil count
      increased, intermittent fever continued. On hospital day 17, blood culture
      yielded fungal colonies indicating S. prolificans. Voriconazole was started
      immediately, but the man's general condition deteriorated with cerebral
      infarction and he died of cerebral hemorrhage on hospital day 65. Attention must
      therefore be paid to the increasing scedosporiosis incidence in Japan.

PMID- 22416482
TI  - [A case of cysticercosis with multiple intracerebral and intramuscular nodular
      lesions].
AB  - A 47-year-old Chinese woman with no significant medical history admitted for
      sudden-onset seizures and transient right homonymous hemianopsia had moved from
      China to Japan 4 years previously. Contrast brain computed tomography (CT) showed
      multiple calcified nodular lesions with surrounding edema, one in the left
      parietal lobe being likely responsible for her visual symptoms. After admission,
      two painful intramuscular nodular lesions were found in her left lower limb.
      Histopathologically biopsy specimens from these lesions were not diagnostic.
      Serum antibody testing (ELISA) for Taenia solium, however, was positive, yielding
      a diagnosis of (neuro) cysticercosis. The woman responded well to albendazole and
      prednisolone treatment. In the two years since discharge, she has not developed
      any new symptoms or seizure recurrence. With increasing global travel, clinicians
      must thus consider the possibility of neurocysticercosis in cases of nodular
      brain lesions in subjects from areas where Taenia solium remains endemic.

PMID- 22416483
TI  - [Antibacterial effect of antibacterial fabrics against multidrug-resistant
      Acinetobacter baumannii complex].

PMID- 22416484
TI  - [Viral isolation and influenza virus antigen detection AH1pdm from stool and
      cerebrospinal fluid].

PMID- 22416485
TI  - Unsteadiness and drunkenness sensations as a new sub-type of BPPV.
AB  - AIM: Benign Paroxysmal Positional Vertigo (BPPV) represents at least 35% of
      vertigo cases and perhaps much more. The aim of this study was to review a
      proposed new type of BPPV which may be detected by using a mechanical assistance
      in BPPV diagnostic and therapeutic maneuvers. MATERIELS AND METHODS: The
      prospective study extracted subjects from 465 patients who presented with some
      positional vertigo or unsteadiness. Only 152 dizzy patients, who presented with
      positional nystagmus but no true vertigo, were included. The TRV armchair permits
      rotation of patients wearing infrared video goggles in all semi-circular planes.
      Treatment effectiveness was defined as absence of symptoms or findings 3 days
      after the therapy sessions. If not initially successful, repeat therapeutic
      sessions were performed or patients underwent further vestibular examination and
      sometime MRI. RESULTS: One hundred nine of the 152 patients demonstrated a low
      level canalithiasis showing nystagmus. Unusual data were collected: Ninety seven
      had a lateral canal and 12 had posterior canal conditions. The average of the
      patients was 62 and they had an average of 1.6 mechanical therapeutic maneuvres
      to reach the success end-point. CONCLUSION: Some patients have persistent
      unsteadiness or drunkenness sensations after being treated by conventional
      maneuvers for BPPV. Often considered a post-BPPV otolithic syndrome an
      alternative possibility is BPPV with a very few otoliths in the lateral canal.
      The therapeutic technique using the mechanical chair permits to improved
      diagnosis of canalithiasis, especially that involving the horizontal canals. Some
      mild dizziness, which may be disabling and chronic can be better investigated and
      treated with mechanical assistance.

PMID- 22416486
TI  - Hypersensitivity to inhalants and food in balance disturbances.
AB  - INTRODUCTION: The prevalence of allergy in patients with Meniere's disease was
      established as approximately 41.6% for inhalants and 26.6% for food. These are
      elevated values in relation to the prevalence of allergy in the general
      population, which varies from 9% to 30% for inhalants (in Brazil) and from 1% to
      3% for food. OBJECTIVES: To evaluate the prevalence of type I hypersensitivity
      reactions to inhalants and food in the patients of the Neurotology Sector of the
      "Hospital das Clinicas" of the University of Sao Paulo Medical School and to
      describe vestibular symptoms of these patients. METHOD: Seventy-five patients
      with imbalance due to peripheral origin were evaluated by a questionnaire for the
      clinical characterization of the cochleo-vestibular symptoms and underwent the
      prick test for 13 inhalants and 5 food stuffs. RESULTS: Twenty-five (33.3%)
      patients presented positive prick tests and, at least, one food allergen. Four
      patients presented positive prick tests without allergy symptoms. The prevalence
      of the complaint of rotatory dizziness was similar among the patients with
      positive and negative prick tests. CONCLUSION: The prevalence of Type I
      hypersensitivity reactions to inhalants and food in the population evaluated was
      greater than in the general population. The vestibular symptoms did not differ
      among the patients with either positive or negative prick tests. However, a
      larger sample size should be obtained for the data to be more reliable and
      compared to a control group.

PMID- 22416487
TI  - Vestibular-evoked myogenic potentials after superior semicircular canal
      obliteration.
AB  - OBJECTIVE: To analyse vestibular evoked myogenic potentials (VEMPs)
      characteristics in patients with superior semicircular canal dehiscence syndrome
      (SCDS) after surgical plugging. MATERIALS AND METHODS: Five surgical plugging of
      SCD were performed on 4 patients presenting uni- or bilateral SCD. VEMPs were
      recorded before and after surgery. RESULTS: Postoperative VEMP testing revealed
      in all cases a normalization of the response on the operated side. DISCUSSION:
      Patients with SCDS typically have VEMPs with pathologically low thresholds and
      large amplitude potentials. VEMPs represent a screening investigation for SSCD
      and a valuable tool in the postoperative follow-up to confirm the successful
      repair of the dehiscence. In bilateral SSCD cases, VEMPs help to localize the
      worst side which is operated first. CONCLUSION: VEMPs are essential in both
      preoperative planning and postoperative monitoring of patients with SCDS.

PMID- 22416488
TI  - Prevalence of and risk factors for obstructive syndrome apnea.
AB  - INTRODUCTION: Obstructive Sleep Apnea Syndrome (OSAS) is becoming an important
      public health problem because of its frequency and adverse health consequences.
      The objective of this prospective study was to evaluate the prevalence of and
      risk factors for OSA in a cohort of subjects working for the french Army.
      SUBJECTS AND METHODS: This prospective study was carried out on a sample of
      volunteers working for the French army. The subjects were recruited at their
      annual work visit between November 2008 and September 2009. Subjects were asked
      to complete 2 screening questionnaires (Epworth and Berlin) and were given a
      medical examination. Subjects suspected of having OSAS (based on high
      questionnaire scores) were monitored by nocturnal ventilatory polygraphy. OSAS
      was diagnosed if the subject was found to have an apnea/hypopnea index (AHI)
      greater than or equal to 5. RESULTS: In this healthy, young and active population
      (n = 1054), 4.20% of subjects were diagnosed with OSA. Comparing our two groups
      of subjects (OSA and non-OSA), several statistically significant (p < .05)
      differences emerged that may be associated with OSA: the individuals with OSA
      were older by an average of 7 years, they presented with an average BMI greater
      than 4.5 kg/m2, an average abdominal girth greater than 12.2 cm and an average
      cervical circumference greater than 2.6 cm. In addition, they consumed more
      tobacco when they were smokers and were more likely to present with permanent
      nasal obstruction. They were also more likely to suffer from gastroesophageal
      reflux and present with skeletal class II. Finally, they presented with a longer
      average soft palate as determined by the Mallampati scoring system. CONCLUSION:
      We found that the major risk factors for OSAS were age, BMI, abdominal girth and
      cervical circumference (linear correlations determined by bi-variate analysis).

PMID- 22416489
TI  - Combined transoral and suprahyoid approach for oropharyngeal cancers: an
      alternative to mandibulotomy.
AB  - Surgical treatment of oropharyngeal tumours usually requires mandibular
      osteotomy. Using this technique allows a better exposure and an easier excision,
      but this approach often generates complications. Since 1995, we used a less
      aggressive surgical technique, with a suprahyoid pharyngotomy when the oral
      approach was not sufficient, thus sparing the mandible. OBJECTIVE: The purpose of
      this study is to evaluate this technical evolution, ensuring that mandibular
      preservation doesn't affect quality of exeresis, local control and survival,
      while allowing a lower complication rate. MATERIAL AND METHODS: All patients who
      have had a surgical treatment for an oropharyngeal carcinoma between 1995 and
      2001 in our center were included in this study. RESULTS: Mandibular sparing was
      used for 55 patients; 19 patients underwent mandibulotomy. The surgical
      procedure's quality was classified as clear, close, or insufficient margins. All
      adjuvant treatments were noted, functional and carcinologic results were
      evaluated. No significant differences are found for exeresis quality and local
      control. There are less complications (p = 0.045) and less surgical revisions (p
      = 0.023) in the preservation group. Survival and functional results are better in
      the preservation group, but without significant difference. For oropharyngeal
      tumours, survival is dependent on tumoural aggressivity, on general condition and
      co-morbidity and on the development of a second tumour. Results in local control
      rate (83.7% at 1 year) are satisfying compared to literature. CONCLUSION:
      Mandibular preservation is an efficient and safe procedure, even for T3/T4
      tumours. Most of oropharyngeal tumours can be removed without mandibulotomy. The
      suprahyoid approach provides a good exposure when oral approach is insufficient,
      thus avoiding mandibulotomy and its complications.

PMID- 22416490
TI  - [Seven cases of inverted nasosinusal papilloma treated at Cotonou].
AB  - OBJECTIVE: Sinonasal inverted papilloma is a rare benign tumor with a high
      recurrence rate and potential malignant transformation. The purpose of this study
      was to analyze the clinical and radiological aspects and to identify the suitable
      surgical approaches to be used in developing countries. METHODOLOGY: In 3 years,
      7 cases have been analyzed in a retrospective study. Patients presented with
      unilateral nasal obstruction and epitasis, a whitish unilateral polypoid mass,
      sinonasal opacity with osteolysis on CT scan or on sinus X-ray. Using these data
      we adopted the Krouse staging which classifies the disease in four stages and
      accordingly the appropriate surgical approach was used. The diagnosis was
      confirmed by histological examination of the biopsied specimen. RESULTS: Average
      age 48.28 years, predominant sex male. Symptom: unilateral nasal obstruction 5,
      bilateral nasal obstruction 1, epistaxis 5. The average time-delay before
      consultation was 73 months. The combined endonasal endoscopic and vestibular was
      the most commonly used approach (4 cases). The results were satisfying. After a
      minimal follow up of 2 years, one case of recurrence was detected after 4 years.
      CONCLUSION: CT scan is an essential tool for the diagnosis and detecting the
      extension of sinonasal inverted papillomas. Better results were obtained with a
      surgical approach that combined a vestibular approach and an endonasal endoscopic
      approach in our region.

PMID- 22416491
TI  - Peritonsillar abscess: is there any evidence of lateralized distribution? An
      analysis of 294 patients.
AB  - OBJECTIVE: Generally, peritonsillar abscess (PTA) occurs only on one side.
      Diseases of paired organs show a distinct asymmetry of occurrence: for instance
      gynaecomastia, varicocele, trigeminal neuralgia, carcinoma of the breast and
      carcinoma of the ethmoid sinus. Therefore, the goal of the present study was to
      investigate a possible dominance of one side in PTA. MATERIAL AND METHOD:
      Lateralization of a PTA was studied in 294 patients treated at Radebeul Hospital
      between January 2004 and December 2009. RESULT: We found only a slight
      predominance of the left side in male as well as female patients. CONCLUSION: The
      cause of the slight asymmetry is unclear. It is also possible that the non
      significant dominance is coincidental.

PMID- 22416492
TI  - [Merkel cell carcinoma of the gingival mucosa in a black young adult].
AB  - Merkel cell carcinoma (MCC) is a rare and aggressive primary neuroendocrine
      neoplasm of the skin with a poor prognosis. It occurs mainly in the skin of white
      elderly patients. Its occurrence in intraoral mucosal sites is rare. We report a
      rare case of MCC that arose in the gingival mucosa of young black adult.

PMID- 22416493
TI  - [Myofibroma of the mandibule: a case report].
AB  - INTRODUCTION: Myofibromatosis is a rare tumor. Two forms are described, solitary
      and multicentric, the solitary type is more common and is localized mainly on the
      head and the neck, mandible involvement is rare. The recent observation of a
      patient with a myofibrome of the mandible has given the opportunity to conduct an
      analysis and review of the literature of this disease rarely encountered.
      MATERIALS AND METHODS: We report a case illustrating solitary myofibroma of the
      mandible in a 16 year old man. RESULTS: The histological diagnosis was done on
      the identification of the spindle-shaped tumoral proliferation and the positive
      expression of the anti-vimentine, anti-smooth, muscle actin anti desmin. The
      treatment was surgical. DISCUSSION: myofibromatosis often presents as a painless,
      well-circumscribed, solid nodule. Imagery is very useful to assess lesion
      extension and for the therapeutic followup. The diagnosis is made on
      anatomopathological findings and immunohistochemical assessment. The treatment of
      the solitary myofibromatosis is primarily surgical and its prognosis is excellent
      contrary to the multicentric form.

PMID- 22416494
TI  - [How I do it: salivary duct preservation in the excision of small oral tumors].
AB  - Benign tumors, in-situ carcinomas and small carcinomas of the anterior floor
      mouth or of the internal surface of the cheek may require resection of salivary
      duct papilla i.e. papilla of submandibular duct or Stensen's duct. If a lymph
      node dissection is not required, excision of submandibular or parotid duct which
      papilla is interested in the resection can be avoided using a surgical technique
      not reported. The authors present two cases illustrating a simple surgical
      proceeding of salivary duct resection/transposition. The present method can be
      used to keep a functional principal salivary gland with an optimal oncologic
      result.

PMID- 22416495
TI  - [Extraction of the esophageal foreign bodies by cervicotomy: our experience about
      9 cases].
AB  - OBJECTIVE: To present our experience of the extraction of the esophageal foreign
      bodies by cervicotomy route. PATIENTS AND METHOD: Descriptive retrospective study
      from 2006 to 2010 realized in the ENT Departments of Yopougon and Treichville's
      Teaching Hospital. RESULTS: 9 (3.3%) of 270 patients underwent surgery to remove
      esophageal foreign bodies. The average age of the patients was of 14.6 years
      (extremes: 8 months and 49 years). The foreign bodies were fish bone, hook of
      clothes peg, medallion, denture and weld. Cervicotomy was performed at once in 4
      cases and after failure of esophagoscopy in 5 cases. There were 2 complications
      (pharyngostoma and suppuration of the operating site). CONCLUSION: The
      cervicotomy must be quickly performed in case of perforation with or without neck
      abscess, sharp or voluminous bodies.

PMID- 22416496
TI  - Training programs and implementation process of positive youth development
      programs.

PMID- 22416497
TI  - Experiential and reflective learning approaches for the train-the-trainers
      program of Project P.A.T.H.S.
AB  - This paper describes the successful application of experiential and reflective
      learning approaches to promote personal and professional growth of social workers
      and teachers in the train-the-trainer program of Project P.A.T.H.S. Qualitative
      data revealed that program participants benefited from their learning
      experiences. The paper inquires into the dilemma of experiential and reflective
      learning. Recommendations are presented for those interested in using
      experiential and reflective approaches for training programs.

PMID- 22416498
TI  - "Use of self" as a strategy in teaching the P.A.T.H.S. curriculum.
AB  - The purpose of promoting "use of self" or "self-disclosures" as a teaching
      strategy in teaching the P.A.T.H.S. curriculum is to create an interactive
      environment between teachers and students which can enhance the interactions
      between both parties. This article focuses on three major consequences of
      utilizing self-disclosures in the education settings, including humanizing the
      classroom, encouraging students' openness, and promoting teachers' awareness and
      reflective practice. Positive feedback of the participants of the Secondary 3
      P.A.T.H.S. training programs show that participants were moved by the training
      instructors, who demonstrated the power of "use of self" in a humanistic manner.
      To retain a humanized and open classroom atmosphere depends greatly on the
      relational exchanges between teachers and students. This revelation should be
      purposeful and intentional, with appropriate boundaries and frequencies.
      Acknowledging the issues to consider in using "use of self" as a teaching
      strategy, teachers should focus attention on the process of connecting students
      with them. Guidelines for worker's self-disclosure are also discussed.

PMID- 22416499
TI  - A review of validated youth prevention and positive youth development programs in
      Asia.
AB  - In view of the intensification of adolescent developmental issues in different
      Asian contexts, there is an urgent need for developing prevention and positive
      youth development programs in different Asian communities. In this paper,
      adolescent prevention and positive youth development programs in Asia which have
      been evaluated by studies adopting true experimental or quasi-experimental
      designs are reviewed. Several observations are highlighted from this review.
      First, compared with Western societies, the number of validated programs in
      different Asian communities was extremely low. Second, there were comparatively
      more programs addressing substance abuse than other mental health problems.
      Third, compared with evaluated prevention programs, there were very few positive
      youth development programs. Finally, there were very few rigorously designed
      evaluative studies of prevention and positive youth development programs over a
      long period of time.

PMID- 22416500
TI  - Subjective outcome evaluation of the Secondary 2 Training Program of the Project
      P.A.T.H.S. in Hong Kong.
AB  - Subjective outcome evaluation findings based on the perceptions of the
      participants who participated in a 3-day training program of the Project
      P.A.T.H.S. are reported in this paper. Results showed that most of the
      respondents were satisfied with and had positive perceptions about the training
      program. They also reported that they were able to acquire attitude, knowledge
      and skills conducive to the successful implementation of the program. In
      addition, the findings suggest that the training program is effective in
      promoting the participants' self-reflections. The present findings provide
      support for the effectiveness of the Secondary 2 Training Program (Experimental
      Implementation Phase) of the Project P.A.T.H.S. in Hong Kong.

PMID- 22416501
TI  - Training evaluation of the Secondary 3 Training Program of the Project P.A.T.H.S.
      in Hong Kong.
AB  - A total of 235 participants from 48 schools participated in a 3-day training
      program designed to train teachers and social workers to implement the Secondary
      3 Program of the Project P.A.T.H.S. in Hong Kong. At the end of the training
      program, participants were invited to respond to a structured subjective outcome
      evaluation questionnaire containing 31 items. The findings revealed that most of
      the respondents had very positive perceptions about the training program and the
      instructors. The present evaluation findings are consistent with the subjective
      outcome evaluation findings in Secondary 1 and Secondary 2 Training Programs,
      which revealed the training program of the Project P.A.T.H.S. generated positive
      reactions, enhanced learning, and desired behavioral changes in the program
      participants.

PMID- 22416502
TI  - Implementation of the Project P.A.T.H.S. in a school with a religious background:
      a case study.
AB  - This paper reports the findings of a case study that attempted to identify school
      related factors influencing the quality of implementation of the Tier 1 Program
      of the Project P.A.T.H.S. in Hong Kong. The case study method was utilized to
      investigate perceptions of the program implementers of program effectiveness, and
      to identify the crucial factors for program success in a school with a religious
      background that admits students with high academic achievement. Findings
      demonstrated that incorporation of the program into the formal curriculum, good
      administrative support, efficient management from school, and presence of
      dedicated teachers contributed to program success. The present findings provide
      insight for the implementation of the Project P.A.T.H.S. in schools with a
      religious background.

PMID- 22416503
TI  - Qualitative evaluation of the Secondary 3 Training Program of the Project
      P.A.T.H.S. in Hong Kong.
AB  - A total of 907 participants from 31 training workshops joined a 3-day training
      program of the P.A.T.H.S. Project (Secondary 3 Program) in Hong Kong. At the end
      of a training workshop, participants were invited to respond to a questionnaire
      assessing what they had learned and experienced in the training workshop, with 31
      structured items and two open-ended questions. Qualitative analyses of the
      participants' responses to the two open-ended questions showed that the
      participants generally had positive evaluation of the instructors, intervention
      program, and the training program, although some suggestions for improvements
      were noted. In conjunction with the quantitative evaluation findings and the
      previous evaluation findings, the present study provides support for the
      effectiveness of the training program for Secondary 3 Program for the potential
      program implementers.

PMID- 22416504
TI  - Implementation of the Project P.A.T.H.S. in Hong Kong: observations based on the
      Co-Walker Scheme.
AB  - The implementation quality of the Tier 1 Program (Secondary 1 Program) of the
      Project P.A.T.H.S. in the third year of the Full Implementation Phase was
      examined in this study, with classroom observations of 233 units in 157 schools.
      Results demonstrated that the overall level of program adherence was generally
      high with an average of 72.96%. A total of 13 aspects regarding program delivery
      were significantly correlated. Multiple regression analyses indicated that
      overall implementation quality was significantly predicted by student
      participation and involvement, classroom control, use of positive and supportive
      feedback, degree of achievement of the objectives, and time management. Student
      participation and involvement, classroom control, degree of achievement of the
      objectives, and time management were significant predictors of success of
      implementation.

PMID- 22416505
TI  - Secondary 1 Training Program of the Project P.A.T.H.S. in Hong Kong: qualitative
      evaluation findings.
AB  - A total of 1177 participants from 45 training workshops joined a 3-day training
      program of the P.A.T.H.S. Project (Secondary 1 Program) in Hong Kong. At the end
      of each training workshop, participants were invited to respond to a
      questionnaire comprising 31 structured items and two open-ended questions which
      assessed what they had learned and experienced in the training workshop.
      Qualitative analyses of the participants' responses to the two open-ended
      questions showed that the participants generally had positive evaluation of the
      training, although some suggestions for improvements were noted. The present
      study, which was based on a sizable sample size, reinforced the previous
      evaluation findings that the Secondary 1 Training Program of the Project
      P.A.T.H.S. in Hong Kong promoted the knowledge and attitudes of the potential
      program implementers.

PMID- 22416506
TI  - Perceptions of adolescents among teachers and social workers in the context of
      training programs in Hong Kong.
AB  - This article explores whether professionals working with young people hold a
      negative view on adolescents in Hong Kong. Data were collected from 1112
      participants from 23 workshops in a 3-day training program of the Project
      P.A.T.H.S. in Hong Kong. In the workshop, there was a group activity inviting the
      participants to describe the characteristics of contemporary young people in Hong
      Kong. The findings showed that positive comments about adolescents were only half
      of the negative comments. The common themes that emerged from the negative
      comments included: "problematic self-conceptions", "do not have long-term life
      goals", "irresponsible", "materialistic", and "calculative". The common themes
      that emerged from the positive comments included: "good at learning new things",
      "energetic", and "creative". The themes apparently reflected sociocultural
      characteristics of the contemporary Hong Kong Society.

PMID- 22416507
TI  - Secondary 1 Training Program of the Project P.A.T.H.S. in Hong Kong: an
      evaluation based on program participants.
AB  - A total of 1744 participants comprising 44 groups participated in a 3-day
      Secondary 1 Training Program of Project P.A.T.H.S. in Hong Kong. At the end of
      the training program, the participants were invited to respond to a subjective
      outcome evaluation. Results showed that the assessment tools are internally
      consistent. Descriptive statistics revealed that evaluations of the respondents
      are positive in terms of the training program content, interaction, trainers'
      performance, self-performance, administrative arrangement, and overall
      satisfaction. Overall satisfaction was predicted by training content, trainers'
      performance, self-performance, and interaction. Training content and trainers'
      performance explain half of the total variance. The present findings reiterate
      other studies regarding the effectiveness of the training program of Project
      P.A.T.H.S. in promoting the participants' knowledge, attitude, and skills in
      delivering the program.

PMID- 22416508
TI  - Tar heel footprints in health care: Carolyn Dunn, PhD, MS.

PMID- 22416509
TI  - Characteristics associated with glycemic control among family medicine patients
      with type 2 diabetes.
AB  - BACKGROUND: As new payment models are developed for chronic diseases such as
      diabetes, there is a need to understand which patient characteristics impact
      glycemic control. This study examines the relationship between patient variables
      and glycemic control, defined as a hemoglobin A1c (A1c) level of <7%, in a cohort
      of family medicine patients with type 2 diabetes. METHODS: A total of 1,398
      medical charts were selected using International Classification of Diseases,
      Ninth Revision, Clinical Modification codes for diabetes. To gather information
      not available through chart review, a survey was used to collect data on
      individual-level characteristics. Information included marital status, education
      level, income level, insurance status, activity level, receipt of diabetes
      education, living arrangement, employment status, and annual income. A cross
      sectional design was used to obtain, via chart review, data about diabetes
      outcomes (ie, A1c level, blood pressure, and low-density lipoprotein cholesterol
      [LDL-C] level). RESULTS: A mailed survey was completed by 669 patients (response
      rate, 47.9%). Almost half of patients in this sample achieved the goal A1c level,
      LDL-C level (ie, <100 mg/dL), and/or blood pressure (ie, <130/<80 mm Hg).
      Medicare insurance (odds ratio [OR], 2.16 [95% confidence interval {CI}, 1.18
      3.96]) and female sex (OR, 1.61 [95% CI, 1.01-2.56]) were associated with
      glycemic control. Other variables, such as annual income, education level, and
      receipt of diabetes education, that were expected to impact glycemic control were
      not significantly associated with an A1c level of <7%. LIMITATIONS: The survey
      response rate was <50%, the study was conducted at a single site, and the chart
      data were retrospective. CONCLUSIONS: Our findings indicate that Medicare
      insurance and female sex were associated with glycemic control. Further
      evaluation is needed to identify determinants that lead to achievement of optimal
      glycemic control among individuals with type 2 diabetes.

PMID- 22416510
TI  - School nurses and children with diabetes: a descriptive study.
AB  - BACKGROUND: Managing diabetes in children is complex. The aims of this
      descriptive study were to describe the care provided to children with diabetes by
      school nurses using case management, to identify differences in care on the basis
      of the workload of the nurse and the age of the child, to explore the role of the
      nurse in responding to emergencies, and to describe the relationship between case
      management and quality of life. METHODS: School nurses completed an expanded
      health assessment. Individualized goals were established and interventions were
      provided on the basis of a protocol. Quantitative and qualitative data for
      children enrolled during the 2009-2010 academic year were analyzed. RESULTS:
      Eighty-six children were enrolled. The most common goals were related to
      establishing a safe school environment. Interventions varied depending on the
      workload of the nurse and the age of the child. Nurses assigned to 1-2 schools
      provided more intervention days (mean, 40.3 days) than did nurses assigned to 3-4
      schools (mean, 24.4 days) (P < .05), particularly in the area of direct care. A
      total of 25 students experienced an emergency at school that initiated a cascade
      of events involving the parent (in 100% of cases), the teacher (in 96%),
      management of hyperglycemia (in 100%), and/or management of hypoglycemia (in
      96%). For teens, case management improved quality of life, particularly the
      ability to communicate with health professionals. LIMITATIONS: The sample was
      small, and there was no comparison group. CONCLUSIONS: School nurses are
      effective in using case management to enhance the health and well-being of
      children with diabetes. This study should be replicated with a larger sample, a
      comparison group, and the inclusion of clinical outcomes.

PMID- 22416511
TI  - Project I See in NC: Initial results of a program to increase access to retinal
      examinations among diabetic individuals in North Carolina.
AB  - BACKGROUND: Diabetic retinopathy is the leading cause of preventable blindness in
      adults. Project I See in NC was begun to determine whether access to eye
      screening for Medicaid recipients and uninsured patients with diabetes in North
      Carolina could be improved. METHODS: We targeted Medicaid recipients and
      uninsured adults with diabetes for screening in 2 Community Care of North
      Carolina Networks. Screenings were performed in primary care settings throughout
      6 counties in the Northwest Community Care Network and 6 counties in Access III
      of Community Care of the Lower Cape Fear. Patients were screened using a high
      resolution digital retinal camera with images read at a centralized reading
      center at Wake Forest School of Medicine. RESULTS: A total of 1,688 patients were
      screened from October 2005 through September 2007. Nearly 15% (282) were found to
      have mild, nonproliferative-to-proliferative retinopathy, while the majority of
      patients had no evidence of diabetic retinopathy. Nearly 12% (196) required
      referral to an ophthalmologist, with 5% (86) requiring urgent referral for
      potentially sight-threatening retinopathy. LIMITATIONS: We were not able to
      confirm which patients kept their ophthalmologic appointments; however, we are
      currently analyzing data from the Medicaid patients in our study who required
      ophthalmologic referral. CONCLUSIONS: Remote digital retinal screening for
      diabetic retinopathy is feasible in primary care settings in both urban and rural
      areas of North Carolina, and it may prove to be an effective means of reaching
      more patients who require annual screening examinations.

PMID- 22416512
TI  - Public health case studies in diabetes prevention and control: innovation,
      partnerships, and funding.
AB  - BACKGROUND: In 2006, we conducted case studies of 4 North Carolina local health
      departments (LHDs) that scored highly on an index of diabetes prevention and
      control performance, to explore characteristics that may serve as barriers or
      facilitators of diabetes prevention and control services. METHODS: Case studies
      involving in-depth interviews were conducted at 4 LHDs. Sites were selected on
      the basis of 2 variables, known external funding for diabetes services and
      population size, that were associated with performance in diabetes prevention and
      control in a 2005 survey of all North Carolina LHDs. Fourteen interviews
      (individual and group) were conducted among 17 participants from the 4 LHDs. The
      main outcome measures were LHD characteristics that facilitate or hinder the
      performance of diabetes programs and services. RESULTS: Interviews revealed that
      all 4 high-performing LHDs had received some sort of funding from a source
      external to the LHD. Case study participants indicated that barriers to
      additional service delivery included low socioeconomic status of the population
      and lack of financial resources. Having a diabetes self-management education
      program that was recognized by the American Diabetes Association appeared to be a
      facilitator of diabetes services provision. Other facilitators were leadership
      and staff commitment, which appeared to facilitate the leveraging of partnerships
      and funding opportunities, leading to enhanced service delivery. LIMITATIONS: The
      small number of LHDs participating in the study and the cross-sectional study
      design were limitations. CONCLUSION: Leadership, staff commitment, partnership
      leveraging, and funding appear to be associated with LHD performance in diabetes
      prevention and control services. These factors should be further studied in
      future public health systems and services research.

PMID- 22416513
TI  - Policy forum: Confronting the diabetes epidemic.

PMID- 22416514
TI  - The state of diabetes in North Carolina.
AB  - The diabetes epidemic is rapidly growing in North Carolina. In 1999, an estimated
      366,000 residents were living with diagnosed diabetes. Ten years later, the
      prevalence of diagnosed cases had increased to approximately 659,000. Diabetes is
      the seventh leading cause of death in the state and decreases life expectancy by
      up to 15 years. If the epidemic remains unchecked in the state, annual health
      care costs are predicted to exceed $17 billion by 2025. Prevention of diabetes
      and diabetes-related complications through treatment and disease self-management
      is paramount in changing this deadly and costly course and demands continued
      innovation in health programs and services and new partnerships among health
      professionals. This article reviews the diabetes burden in North Carolina and
      sets the stage for commentaries and sidebars in the accompanying policy forum.

PMID- 22416515
TI  - How does the Affordable Care Act support children at risk for or with diabetes?
AB  - The Affordable Care Act (ACA) brings our nation closer to the goals of universal,
      continuous, adequate, and affordable coverage for all children. This commentary
      discusses the expected outcomes and the potential challenges in the ACA
      legislation that affect access, coverage, and use of health care services by
      North Carolina children with diabetes.

PMID- 22416516
TI  - ENERGIZE! A community-based lifestyle intervention targeting at-risk, overweight
      children.

PMID- 22416517
TI  - Diabetes in North Carolina: descriptive epidemiology and meaningful use of
      electronic health records.
AB  - Diabetes is a major public health problem in North Carolina, affecting all
      sociodemographic groups. This commentary examines diabetes incidence, prevalence,
      disparities, morbidity, mortality, and costs. It also facilitates discussion
      about how the meaningful use of electronic health records can create new
      opportunities for collaboration between public health and clinical care
      professionals and organizations.

PMID- 22416518
TI  - Facilitating self-management of diabetes through education: the North Carolina
      case.
AB  - Self-management education is such a critical part of diabetes care that medical
      treatment without it is considered inadequate. This article discusses the North
      Carolina Diabetes Education Recognition Program and calls for expansion of this
      program through local health departments.

PMID- 22416519
TI  - Hospital-based self-management of diabetes.

PMID- 22416520
TI  - Use of integrated care delivery to improve the quality of diabetes management
      among African Americans.
AB  - The prevalence of type 2 diabetes is increasing, and racial disparities in that
      prevalence persist. Reimbursement policies do not match the innovative care
      delivery systems that have been developed. One key policy goal involves
      reimbursement for diabetes care delivered by physician and nonphysician health
      care professionals on the same day. Our evidence suggests that this integrated
      care improves outcomes among patients.

PMID- 22416521
TI  - Barriers to diabetes prevention and control among American Indians.
AB  - North Carolina's American Indian population experiences a disproportionate
      diabetes burden, in terms of both a high prevalence of the disease and excess
      diabetes-related death and disability. Concerted efforts need to be made to
      provide culturally appropriate and easily accessible education, health care, and
      health-promoting resources in these vulnerable communities.

PMID- 22416522
TI  - Cherokee choices: a diabetes prevention program in Cherokee, North Carolina.

PMID- 22416523
TI  - Community-based prevention and control of diabetes among North Carolina Latinos.
AB  - El Centro Hispano is a grassroots community-based organization dedicated to
      strengthening the Latino community and to improving the quality of life among
      Latino residents in central North Carolina. This article discusses El Centro
      Hispano's role in providing culturally and linguistically appropriate education,
      outreach, and referrals to prevent and control diabetes among Latinos.

PMID- 22416524
TI  - Peer-to-Peer learning in the self-management of chronic disease.

PMID- 22416525
TI  - Diabetes and adverse mental health among African Americans.
AB  - This article reviews the connection between diabetes and adverse mental health
      among African Americans. Concern about safe insulin prescribing and
      administration is raised, and the importance of integrated physical and mental
      health care in the prevention and control of diabetes is highlighted.

PMID- 22416526
TI  - Could hearing loss be the link between diabetes and depression?
AB  - Hearing loss is isolating and embarrassing and can cause or exacerbate
      depression. This article advocates that diabetes educators receive training from
      an audiologist so that they can screen for hearing loss in people with diabetes
      and refer individuals with suspected hearing loss to audiologists for treatment.

PMID- 22416527
TI  - Translating diabetes prevention programs: implications for dissemination and
      policy.
AB  - Numerous studies have translated the Diabetes Prevention Program (DPP) for
      community-based settings, and the results are encouraging. This commentary
      discusses one community-based DPP translational study, Healthy Living
      Partnerships to Prevent Diabetes, in detail, as well as the implications of DPP
      translational studies for public policy.

PMID- 22416528
TI  - Innovative approaches to reduce diabetes costs.
AB  - According to the American Diabetes Association, the cost of treating diabetes in
      North Carolina was approximately $5.3 billion in 2006. Reigning in diabetes
      related costs requires collaboration between third-party payers, health care
      professionals, and people with diabetes. This article reviews innovative policy
      changes that affect all 3 groups and are intended to improve diabetes-associated
      care and costs.

PMID- 22416529
TI  - Prevalence of diabetes-related eye disease in North Carolina: findings from the
      North Carolina Behavioral Risk Factor Surveillance System.

PMID- 22416530
TI  - The role of allied health in health care reform.
AB  - The wide-ranging and significant disciplines representing allied health
      constitute the largest and one of the most rapidly growing health care workforces
      in North Carolina. With anticipated increases in patients' access to care, allied
      health professionals will need to call on their full scope of practice as part of
      a comprehensive health care team.

PMID- 22416531
TI  - Moving medicine forward in North Carolina.

PMID- 22416532
TI  - Embracing ethical principles for nursing education.

PMID- 22416533
TI  - Nursing process and clinical reasoning.

PMID- 22416534
TI  - Confidence and knowledge regarding ethics among advanced practice nurses.
AB  - As the scope of advanced practice nursing expands and the educational
      requirements increase, so do the ethical responsibilities. How prepared are
      advanced practice nurses (APNs) to manage the ethical challenges in advanced
      practice? The purpose of this study was to determine APNs' ethics knowledge and
      perceived level of confidence in their ability to manage ethical problems in
      advanced practice. Assuming ethics knowledge and abilities of APNs are similar to
      those of medical residents, a survey instrument for medical residents was
      modified for use with APNs. Responses to the modified survey indicated a fairly
      high level of confidence but a fairly low level of knowledge. Studies show that
      ethics education can be effective in improving knowledge, confidence, and ethical
      behavior. Given the expanding role of APNs as doctors of nursing practice,
      research is needed to determine the ethics knowledge needs and teaching
      strategies to better prepare nurses for the challenges of advanced practice.

PMID- 22416535
TI  - Student perceptions of incivility in nursing education: implications for
      educators.
AB  - This study explored the phenomenon of incivility in nursing education from the
      perspective of undergraduate nursing students and compared it to perspectives of
      educators as found in the literature. The sample consisted of 24 undergraduate
      junior and senior nursing students from four universities in the mid-Atlantic
      states. Data from four focus groups were transcribed and content analyzed to
      reveal themes and subthemes. Students perceived that incivility in nursing
      education exists. They shared a common view with findings in the literature
      regarding incivility from the faculty perspective. Notably, an emerging student
      view was that faculty may contribute to the escalating incivility in nursing
      education, and that student incivility is justified when faculty are seen as
      uncivil. The implications for educators, consistent with the literature, are that
      students want professors to maintain classroom decorum and set the example for
      civility.

PMID- 22416536
TI  - Can't we all just get along? A primer on student incivility in nursing education.
AB  - Student incivility is a growing problem in the academic nursing community. The
      purpose of this study was to identify factors associated with the increasing
      prevalence of incivility among nursing students. Various databases (Allied and
      Complimentary Medicine, Cumulative Index to Nursing and Allied Health Literature,
      and Ovid MEDLINE) were queried using the key words incivility, student
      incivility, nursing education, student-faculty relations, student aggression, and
      student violence. Both research- and non-research-based articles were selected
      for review. Also included among the references retrieved were articles pertaining
      to unethical conduct and disruptive behavior. Virtually all of the articles
      characterized incivility as the product of a symbiotic relationship between
      students and faculty. Fundamentally, incivility was found to be a multifaceted
      problem whose resolution is predicated on gaining a heightened understanding of
      the economic, sociological, and psychological underpinnings of disruptive
      behavior.

PMID- 22416537
TI  - The journey to nursing professionalism: a learner-centered approach.
AB  - This article reports on a biannual baccalaureate nursing program designed to
      concentrate student learning on the tenets of professionalism in nursing. A
      seminar structure is used to promote student interaction, the exploration of
      professional issues, and critical thinking. Miller's Wheel of Professionalism in
      Nursing provides a framework for discussion of professional concepts in nursing.
      Several teaching-learning strategies are used, including a short slide show,
      interactive lectures by area experts, and student-led group discussions of
      scenarios based on the elements of professionalism illustrated by Miller. Use of
      Miller's framework and these various educational strategies yielded greater
      faculty satisfaction and student participation than witnessed in previous years,
      resulting in a deeper foundation for professional behavior development throughout
      the curriculum.

PMID- 22416538
TI  - An integrative literature review of study abroad programs for nursing students.
AB  - Nurse researchers need to explore study abroad programs and identify their impact
      on the development of cultural competence and global perspectives in nursing
      students. Despite the anecdotal professional and personal benefits that have been
      attributed to study abroad in other disciplines, current nursing literature
      regarding this topic is limited and has only emerged in nursing research within
      the last decade. There is a significant gap in the existing body of knowledge
      with respect to American nursing students who study abroad and the reported
      benefits of and impediments to their experiences. Much of the nursing research
      conducted with American nursing students has been quantitative as opposed to
      qualitative studies with European and Australian nursing students. Many samples
      are homogenous and therefore exclude diverse populations. Further research
      involving all methodological designs is warranted to better understand this type
      of engaged learning.

PMID- 22416539
TI  - Identifying strengths and weaknesses in the utilization of Objective Structured
      Clinical Examination (OSCE) in a nursing program.
AB  - Objective Structured Clinical Examination (OSCE) is used in nursing to assess
      students' transfer of classroom and laboratory learning experiences into
      simulated clinical practice. OSCE is a performance-based exam in which students
      are observed demonstrating a multitude of clinical behaviors. The purpose of this
      study was to identify strengths and weaknesses in the utilization of OSCE in this
      nursing program with 60 full-time students ages 21 to 23. An evaluation
      methodology was used for this study. Interviews were conducted with two groups:
      faculty facilitators of OSCE and standardized patients (SPs). Areas of focus
      were: data collection of students' performance, SP selection and training, and
      modification of the Nursing Interview Interaction Scale (NIIS). It was found that
      with appropriate SP selection and training, utilization of appropriate tools, and
      good data collection, OSCE can offer a valid and reliable means of testing
      nursing students' clinical competencies.

PMID- 22416540
TI  - Lessons learned from an accelerated post-master's nurse educator certificate
      program: teaching the practicum course.
AB  - Nursing faces current and future shortages in the practice arena. The nurse
      educator shortage exacerbates the nursing shortage.This article describes an
      innovative and collaborative approach developed to increase the supply of nurse
      educators. An overview of the initial offering of this post-master's nurse
      educator certificate program, a grant-funded, cohort-based program, delivered
      online in an accelerated format, is provided. Particular attention is given to
      the nursing education practicum, a precepted teaching experience. This course is
      viewed as a culminating course, wherein the role transition from expert
      practitioner to novice educator occurs as students connect the experiential
      aspects of the practicum with knowledge gained in didactic courses and enter a
      new community of practice. Lessons learned and recommendations for future cohorts
      are discussed.

PMID- 22416541
TI  - NURSING 911: an orientation program to improve retention of online RN-BSN
      students.
AB  - This article describes the implementation and evaluation of an eight-hour,
      comprehensive, face-to-face orientation program designed to improve student
      retention in a newly developed online RN to BSN program. A total of 179 newly
      enrolled RN to BSN students participated in the orientation program and evaluated
      the process. Student attrition decreased from 20 percent to less than 1 percent
      after the orientation program was extended and improved to include a technology
      assessment and an online practice course. A quality online program requires a
      well-designed orientation that includes technological assessments and hands-on,
      active participation by the learner. The newly improved and designed course has
      become effective in student retention and transition into the online learning
      environment.

PMID- 22416542
TI  - My 2012 to-do list for teaching, research, and scholarship.

PMID- 22416543
TI  - Synchronous online role play for enhancing community, collaboration, and oral
      presentation proficiency.

PMID- 22416544
TI  - Engaging nursing students through integration of the audience response system.

PMID- 22416545
TI  - NLN ethical principles for nursing education.

PMID- 22416546
TI  - Miami Dade College faculty support their nursing faculty colleagues in Haiti.

PMID- 22416547
TI  - Precepting PA students: how you can touch the future.

PMID- 22416548
TI  - Phenytoin: an old friend that still confuses us.

PMID- 22416549
TI  - Lesions that continue to recur in the same place. Fixed drug eruption (FDE).

PMID- 22416550
TI  - Antimicrobial stewardship: a proactive approach to combating resistance.

PMID- 22416551
TI  - The SNAP treatment approach for children with acute otitis media.

PMID- 22416552
TI  - Seizures induced by hot water in an otherwise healthy 18-month-old boy.

PMID- 22416553
TI  - An anti-inflammatory diet: the next frontier in preventive medicine.

PMID- 22416554
TI  - Management of migraine headache: an overview of current practice.

PMID- 22416555
TI  - Perceptions of physician assistants regarding a specialty certification
      examination.
AB  - A national sample of physician assistants (PAs) responded to a survey about their
      perceptions of specialty certification. Fewer than one-third planned to certify.
      Of three factors, advantage of specialization was most related to awareness,
      plans to certify, and demographics. Respondents were unsure whether certification
      would increase PA salaries. Many felt specialty certification will be the undoing
      of the profession.

PMID- 22416556
TI  - Perceptions of physician assistants regarding direct-to-consumer advertising.
AB  - Of 1,254 practicing physician assistants (PAs) who completed a survey, 91% were
      familiar with direct-to-consumer advertising (DTCA). When asked about their
      general perception, 96% of PAs were neutral or unfavorable towards DTCA. PAs felt
      that DTCA encouraged patients to make atypical medication requests, overlook the
      PA's medical opinion, and seek other health care providers.

PMID- 22416557
TI  - When does treatment of subclinical hypothyroidism reduce cardiovascular risk?

PMID- 22416558
TI  - Triple therapy for hepatitis C.

PMID- 22416559
TI  - Surrogate decision makers: what if a surrogate cannot decide?

PMID- 22416560
TI  - An acute elbow injury after a fall at the playground.

PMID- 22416561
TI  - Midnight medicine: a time when difficult decisions must be made.

PMID- 22416562
TI  - What is your diagnosis? Avascular necrosis of the femoral head.

PMID- 22416563
TI  - Disability rights at the crossroads.

PMID- 22416564
TI  - Modern guardianship: legal and clinical perspectives.

PMID- 22416565
TI  - Confronting violence, protecting health.

PMID- 22416566
TI  - Settled precepts: normative ethics, applied ethics and physician complicity with
      torture.

PMID- 22416567
TI  - Reflections on peace-through-health: the first Canadian, Israeli and Palestinian
      maternal and child health programme for medical students.

PMID- 22416568
TI  - Post 9/11 Somalia: the strategic role of health systems strengthening in global
      security.

PMID- 22416569
TI  - Impact of sexual violence on children in the Eastern Democratic Republic of
      Congo.
AB  - The conflict in the Eastern Democratic Republic of Congo (DRC) has been
      particularly devastating for children and has been typified by high levels of
      sexual and gender-based violence (SGBV). In this study, we seek to characterize
      the patterns and impact of sexual violence on children in the Eastern DRC. Semi
      structured questionnaires were administered among a convenience sample of women
      <18 years of age presenting for post-sexual-violence care at Panzi Hospital in
      South Kivu, DRC. Analysis included quantitative and qualitative methods to
      describe the characteristics of the violence, perpetrators, and survivors and to
      illuminate common themes within the narratives. A total of 389 survivors of SGBV
      under the age of 18 were interviewed between 2004 and 2008. These paediatric
      survivors were more likely than adult survivors to have experienced gang rape,
      been attacked by a civilian perpetrator, and been assaulted during the day.
      Survivor and perpetrator characteristics were further stratified by type of
      attack. Reports of violence perpetrated by civilians increased 39-fold while
      reports of violence perpetrated by armed combatants decreased by 70% between 2004
      and 2008. Qualitative analysis of the narratives revealed common themes, such as
      physical signs and symptoms among SGBV survivors (23.9%), pregnancy resulting
      from rape (19.3%), perpetrators being brought to justice (18.3%), and
      neighbourhood men as perpetrators (17.7%). Children in the Eastern DRC continue
      to face significant threats of sexual violence. By understanding the patterns of
      this violence, local and international approaches could be more effectively
      implemented to protect these vulnerable children.

PMID- 22416570
TI  - Sexual and gender based violence against men in the Democratic Republic of Congo:
      effects on survivors, their families and the community.
AB  - Media and service provider reports of sexual and gender based violence (SGBV)
      perpetrated against men in armed conflicts have increased. However, response to
      these reports has been limited, as existing evidence and programs have primarily
      focused on prevention and response to women and girl survivors of SGBV. This
      study aims to contribute to the evidence of SGBV experienced by males by
      advancing our understanding of the definition and characteristics of male SGBV
      and the overlap of health, social and economic consequences on the male survivor,
      his family and community in conflict and post-conflict settings. The qualitative
      study using purposive sampling was conducted from June-August 2010 in the South
      Kivu province of Eastern DRC, an area that has experienced over a decade of armed
      conflict. Semi structured individual interviews and focus group discussions were
      conducted with adult male survivors of SGBV, the survivors' wife and/or friend,
      health care and service providers, community members and leaders. This study
      found that SGBV against men, as for women, is multi-dimensional and has
      significant negative physical, mental, social and economic consequences for the
      male survivor and his family. SGBV perpetrated against men and boys is likely
      common within a conflict-affected region but often goes unreported by survivors
      and others due to cultural and social factors associated with sexual assaults,
      including survivor shame, fear of retaliation by perpetrators and stigma by
      community members. All key stakeholders in our study advocated for improvements
      and programs in several areas: (1) health care services, including capacity to
      identify survivors and increased access to clinical care and psychosocial support
      for male survivors; (2) economic development initiatives, including microfinance
      programs, for men and their families to assist them to regain their productive
      role in the family; (3) community awareness and education of SGBV against men to
      reduce stigma and discrimination and increase acceptance of survivors by family
      and larger community.

PMID- 22416571
TI  - Polymeric surface-mediated, high-density nano-assembly of functional protein
      arrays.
AB  - The exploding field of biomedical research and biotechnology demands convenient
      and reliable solid-state methods for protein detection and underscores the
      importance of high-density, high-payload protein arrays assembled on two
      dimensional platforms. Proteins immobilized on various polymeric surfaces are of
      particular importance in basic research and biomedical applications as surface
      bound proteins on polymers are routinely utilized in numerous biological
      measurements in laboratory and clinical settings. Specifically, protein
      nanoarrays can function effectively as low-cost, miniaturized, and small-volume
      assay platforms. In this paper, top-down and bottom-up approaches to assemble
      functional protein arrays are discussed in depth, while focusing on the recent
      contributions from the nanoscience field to protein assembly on polymeric
      surfaces. Research endeavors to improve the density, uniformity, stability, and
      biological activity of surface-bound proteins on polymers are outlined.
      Biosensing applications of such systems and the associated challenges of
      quantitative and analytical detection are addressed. In addition, the future
      outlook of the applications of nanoscale polymer-based, solid-phase protein
      detection is provided.

PMID- 22416572
TI  - Targeted delivery of methotrexate to tumor cells using biotin functionalized
      methotrexate-human serum albumin conjugated nanoparticles.
AB  - Systemic toxicity following cancer chemotherapy is an important concern. Targeted
      drug delivery systems could reduce the toxicity of anticancer drugs. Vitamins
      have been considered as targeting moieties in novel cancer treatment strategies.
      In this study, biotin was attached to nanoparticles of conjugated methotrexate
      human serum albumin. Biotin functionalized methotrexate-human serum albumin with
      three different amounts of biotin attached to the nanoparticles were prepared. It
      was shown that the cytotoxicity of biotin functionalized nanoparticles on T47D
      and HeLa tumor cells was significantly higher than that of free methotrexate and
      non-functionalized nanoparticles. The cytotoxicity of biotin functionalized
      nanoparticles further increased when the number of biotin molecules attached on
      the surface of nanoparticles increased. The uptake of FITC labeled biotin
      functionalized nanoparticles by T47D and HeLa cells measured by flow cytometry,
      was also higher than that of non-functionalized nanoparticles. It can be
      concluded that the biotin functionalized methotrexate-human serum albumin
      conjugated nanoparticles could be used as a potent drug for specific delivery of
      methotrexate to tumors.

PMID- 22416573
TI  - A new assay for CCR5del32 mutation: genotyping through the number of fragments
      amplified.
AB  - CCR5 is a coreceptor for the entry of HIV into CD4+ cells and some of its natural
      mutants possess potential protection against HIV-1 infection. Individuals with
      the CCR5-delta32 genotype have a lower possibility of being infected with HIV and
      take longer to progress to AIDS if infected. The present study demonstrated a new
      primer extension assay for genetic analysis of the CCR5del32 mutation: each
      genotype is determined by a specific number of fragments amplified. Quick and
      efficient screening and testing of this specific genotype is clinically useful in
      epidemiological study, risk analysis, and determining donors for allogenic stem
      cell transplantation.

PMID- 22416574
TI  - Hydroxyapatite-alginate nanocomposite as drug delivery matrix for sustained
      release of ciprofloxacin.
AB  - Hydroxyapatite is a bioceramic which has a wide range of medical application for
      bone diseases. To enhance its usage, we have prepared ciprofloxacin loaded nano
      hydroxyapatite (HA) composite with a natural polymer, alginate, using wet
      chemical method at low temperature. The prepared composites were analyzed by
      various physicochemical methods. The results show that the nano HA crystallites
      are well intact with the alginate macromolecules. For the composite system FT-IR
      and micro Raman results are reported in this paper. Studies on the drug loading
      and drug release have been done. The drug is pre-adsorbed onto the ceramic
      particle before the formation of composite. The thermal behavior of composite has
      been studied using thermo gravimetric analysis (TGA). This work, reports that the
      nanocomposite prepared under optimum condition could prolong the release of
      ciprofloxacin compared with the ciprofloxacin loaded hydroxyapatite.

PMID- 22416575
TI  - Adenoviral vectors modified by heparin-polyethyleneimine nanogels enhance
      targeting to the lung and show therapeutic potential for pulmonary metastasis in
      vivo.
AB  - Polyethyleneimine (PEI) is a well-known cationic polymer that has previously been
      shown to have significant potential to deliver genes in vitro and in vivo.
      However, PEI is non-degradable and exhibits a high cytotoxicity as its molecular
      weight increases. The clinical application for systemic administration of
      adenoviral (Ad) vectors is limited, as these vectors do not efficiently penetrate
      solid tumor masses due to a common deficiency of Coxsackie Adenovirus Receptor
      (CAR) on the tumor surface. In this study, we conjugated low molecular weight PEI
      (Mn = 1,800) to heparin (Mn = 4,000-6,000) to create a new type of cationic
      degradable nanogel (HPEI) that was then used to modify Ad vectors. The resulting
      HPEI-Ad complexes were used to infect CT26 and HeLa cells in vitro. Additionally,
      the HPEI-Ad complexes were administrated in vivo via intravenous injection, and
      tissue distribution was assessed using luciferase assays; the therapeutic
      potential of HPEI-Ad complexes for pulmonary metastasis mediated by CT26 cells
      was also investigated. In vitro, HPEI-Ad complexes enhanced the transfection
      efficiency in CT26 cells, reaching 36.3% compared with 0.1% of the native
      adenovirus. In vivo, HPEI-Ad complexes exhibited greater affinity for lung tissue
      than the native adenovirus and effectively inhibited the growth of pulmonary
      metastases mediated by CT26 cells. Our results indicate that Ad vectors modified
      by HPEI nanogels to form HPEI-Ad complexes enhanced transfection efficiency in
      CT26 cells that lacked CAR, targeted to the lung and demostrated a potential
      therapy for pulmonary metastasis.

PMID- 22416576
TI  - A silicon dioxide modified magnetic nanoparticles-labeled lateral flow strips for
      HBs antigen.
AB  - Herein we reported a new type of silicon dioxide wrapped magnetic nanoparticles
      labeled lateral flow strip for detection of HBs antigen in sera. The SiO2 wrapped
      Fe3O4 nanocomposites were prepared and characterized by HR-TEM, FTIR and
      magnetometer. As-prepared nanocomposites were used to label anti-HBV surface
      monoclonal antibody, the lateral flow strips were constructed, and 100 specimens
      of sera were collected and tested. Results showed that the prepared SiO2 wrapped
      Fe3O4 nanocomposites were shell/core structure, well dispersed, with the size of
      25 nm in diameter, the thickness of the shell was about 3 nm, their magnetic
      saturation intensity was 44.3 meu g(-1). Clinical sera specimens test results
      showed that the prepared lateral flow strips were with the detection limitation
      of 5 pg/mL by naked eye observation, and 0.1 pg/mL by CCD reader or MAR Analyzer,
      specificity was 100%. In conclusion, one kind of silicon dioxide wrapped magnetic
      nanoparticles-labeled lateral flow strip for ultrasensitive detection of HBs
      antigen was successfully developed, its ease of use, sensitiveness and low-cost
      make it well-suited for population-based on-the-site hepatitis B screening.

PMID- 22416578
TI  - Nanosized controlled surface pretreatment of biometallic alloy 316L stainless
      steel.
AB  - Stainless steel (AISI 316L) is a medical grade stainless steel alloy used
      extensively in medical devices and in the biomedical field. 316L stainless steel
      was successfully electropolished via an ecologically friendly and biocompatible
      ionic liquid (IL) medium based on Vitamin B4 (NB4) and resulting in nanosized
      surface roughness and topography. Voltammetry and chronoamperometry tests
      determined optimum polishing conditions for the stainless steel alloy while
      atomic force microscopy (AFM) and scanning electron microscopy (SEM) provided
      surface morphology comparisons to benchmark success of each electropolishing
      condition. Energy dispersive X-ray analysis (EDX) combined with SEM revealed
      significantly smoother surfaces for each alloy surface while indicating that the
      constituent metals comprising each alloy effectively electropolished at uniform
      rates.

PMID- 22416577
TI  - Nanoparticle delivery systems formed using electrically sprayed co-flowing
      excipients and active agent.
AB  - The high production rate generation of drug-loaded biodegradable nanoparticles is
      a crucial factor in achieving significant and rapid advances in nanomedicine. In
      this paper, we report a one-step, high yield, coaxial electrohydrodynamic
      spraying method for generating insulin-loaded polymeric nanoparticles.
      Poly(lactic-co-glycolic acid) copolymer (PLGA) was used as the model
      biodegradable polymer. The particle shape and size-distribution were studied
      using electron and atomic force microscopy and were also subjected to degradation
      and in vitro insulin release studies for up to five weeks. Nanoparticles as small
      as 50 nm were produced at the ambient temperature with an encapsulation
      efficiency of 80 +/- 4.1%, through manipulation of simple process control
      variables (flow rate, applied voltage and collection point). On spraying, insulin
      loaded PLGA nanoparticles were generated without disruption to the insulin
      structure. By using small amounts of a biocompatible hydrophilic additive, the
      insulin burst release was reduced by 20% and 15% on the first and second days,
      respectively, and this was followed by comparatively sustained release over 3
      weeks. Coaxial electrohydrodynamic spraying was shown to produce insulin-loaded
      PLGA, with and without the addition of excipients in a single step; with 85% of
      particles <100 nm at a polymer concentration of 2 wt%. These insulin-loaded PLGA
      nanoparticles have the potential to maintain the level of drug release over 3
      weeks.

PMID- 22416579
TI  - Construction of rice site-specific chloroplast transformation vector and
      transient expression of EGFP gene in Dunaliella salina.
AB  - Chloroplast is a new hotspot in the field of plant transformation system of plant
      genetic engineering. Plastid transformation has several advantages: high
      expression, multiple expressed genes in a single transformation event, absence of
      gene silencing, et al. A series of elements for construction of dicistronic site
      specific integration expression vector of rice chloroplast have been cloned,
      including trnl-trnA (rice chloroplast homologous recombination fragments), Prrn
      (16S rRNA operon promotor), PpsbA (the 3' untranslated region of the
      chloroplastpsbA gene), hptll gene (encoding hygromycin phosphotransferase) and
      EGFP (encoding enhanced green fluorescence protein). All the elements were
      constructed into a rice chloroplast dicistronic expression vector pCTE04 (-trnl
      Prrn-RBS-hptlI-RBS-EGFP-PpsbA- trnA-). Then pCTE04 was introduced into
      chloroplasts of Dunaliella salina through particle bombardment. Strong green
      fluorescence was observed in chloroplasts of some bombarded Dunaliella salina
      cells under a stereo fluorescence microscope, indicating that pCTE04 could be
      expressed in Dunaliella salina chloroplasts transiently. It provides a solid
      foundation for further genetic engineering in rice chloroplast transformation.

PMID- 22416580
TI  - Single nucleotide polymorphisms analysis of noise-induced hearing loss using
      three-dimensional polyacrylamide gel-based microarray method.
AB  - Noise induced hearing loss (NIHL) is a complex occupational hazard caused by an
      interaction between genetic and environmental factors. Millions of Chinese
      industrial people are daily exposed to high level of noise. Although the
      environmental risk factors have been studied extensively, the nature of the
      genetic factors contributing to HIHL has not yet been clarified. In this study,
      we investigated 15 single nucleotide polymorphisms (SNPs) in 6 candidate genes
      influence susceptibility to noise in Chinese noise-exposed workers. Data from 3
      dimensional polyacrylamide gel-based microarray platforms were analyzed. 103
      blood samples were collected from noise-exposed laborers in Ningbo, Zhejiang,
      China. Subsequently, the interaction between noise exposure and genotypes and
      their effect on NIHL were analysed using logistic regression. Two interesting
      results were observed between noise exposure levels and genotypes of three SNPs,
      hence confirming that they are NIHL susceptibility genes in Chinese population.

PMID- 22416581
TI  - Interaction of ZnO nanoparticles with microbes--a physio and biochemical assay.
AB  - The antibacterial activity of ZnO nanoparticles (nano ZnO) on various
      microorganisms has been investigated in this study and acting mechanism is
      proposed for E. coli a model organism by analyzing the growth, permeability and
      morphology of the bacterial cells. The experimental results indicated 1 mmoL
      (81.4 microg) nano ZnO could completely inhibit the growth of 10(7) cfu/mL
      bacterial cells in liquid Luria-Betrani medium. In the biochemical study, it has
      been observed that, nano ZnO resulted in the leakage of proteins.
      Chemiluminescence assay proved the generation of the reactive oxygen species into
      active state. When the cells of E. coli were exposed to nano ZnO, many pits were
      observed in bacterial cells by TEM and Fluorescence microscopy and the cells were
      found to be fragmentary. Released zinc ion from has been monitored by AAS. It
      suggested that nano ZnO is able to destroy the permeability of the bacterial
      membranes. Our study demonstrated that nano ZnO damages the structure of
      bacterial cell membrane and depressed the activity of some membranous enzymes by
      ROS production which caused E. coli bacteria to die eventually.

PMID- 22416582
TI  - Induction of cell migration in vitro by an electrospun PDGF-BB/PLGA/PEG-PLA
      nanofibrous scaffold.
AB  - Electrospinning is a versatile technique used to fabricate potential tissue
      engineering scaffolds with a structure similar to the native extracellular matrix
      (ECM). In this study, Platelet-Derived Growth Factor (PDGF)-BB with BSA as a
      carrier protein was incorporated into an electrospun PLGA/PEG-PLA composite
      scaffold for induction of cell migration, an early process necessary for tissue
      regeneration and wound healing. Incorporating PDGF-BB into the fibers did not
      change the overall morphology of the scaffold, with the exception of a slight
      increase (approximately 12%) in the number of fibers with diameters ranging from
      1-100 nm. Following a strong burst of release during the initial 24 hours,
      approximately 20% of the total incorporated PDGF-BB was released from the
      scaffold over 5 days, as determined by ELISA. The presence of the released PDGF
      BB was also confirmed via SDS-PAGE. Using an in vitro agarose-cell migration
      assay with MC3T3 pre-osteoblastic cells, the preserved bioactivity of the
      released PDGF-BB was demonstrated via its ability to stimulate robust cell
      migration, equivalent to that of pure unincorporated (control) PDGF-BB. Overall,
      this study demonstrates that it is feasible to incorporate and deliver bioactive
      PDGF-BB via an electrospun scaffold for potential tissue repair applications,
      especially as a potent inducer of cell migration.

PMID- 22416583
TI  - Effect of functionalization of carbon nanotubes with psychosine on complement
      activation and protein adsorption.
AB  - Carbon nanotubes possess interesting physicochemical properties which make them
      potentially usable in medicine. Single-walled carbon nanotubes and multi-walled
      carbon nanotubes, for example, may carry and deliver anticancer drugs, such as
      cisplatin. Magnetic nanoparticles, like iron filled MWCNT, can be used in
      hyperthermia therapy. However, their hydrophobic character is a major difficulty,
      as preparation of stable dispersions of carbon nanotubes in biological buffers is
      an essential step towards biomedical applications. Recently, a novel treatment
      using the glycolipid, Galactosyl-beta1-sphingosine (psychosine), was employed to
      make stable suspensions of psychosine-functionalized carbon nanotubes in
      biological buffers. In this paper, the interactions of psychosine-functionalized
      carbon nanotubes with a part of the human immune system, complement, is
      presented. To investigate if human serum complement proteins can interact with
      psychosine-functionalized carbon nanotubes, complement consumption (depletion)
      assays were conducted. Moreover, direct protein binding studies, to analyze the
      interaction of plasma proteins with the psychosine-functionalized carbon
      nanotubes, using affinity chromatography and sodium dodecyl sulphate
      polyacrylamide gel electrophoresis techniques, were applied. The psychosine
      functionalized carbon nanotubes activate human complement via the classical
      pathway. Interestingly, as the hydrophilic part of the glycolipid may bind to
      ficolins, the lectin pathway could also be involved. Binding of human plasma
      proteins is very selective as only very few proteins adsorb to the psychosine
      functionalized carbon nanotube surface, when placed in contact with human plasma.
      Bovine serum albumin-coated carbon nanotubes were used as a standard to find the
      differences in complement activation and protein adsorption patterns, caused by
      various non-covalent coatings of carbon nanotubes.

PMID- 22416584
TI  - Enhanced agglutination reaction of ABO subgroups by gold nanoparticle solution:
      implication for identification of ABO subgroups.
AB  - Although the ABO blood group is the most significant in blood group system in
      human, other subgroups system is also important to be concerned in blood banking
      laboratory. ABO subgroups have weak antigen potency on red blood cell. In some
      cases, they could not been detected by cell grouping and serum grouping methods.
      This may lead to misinterpretation of ABO typing which will cause serious
      problems for transfusion and transplantation. Gold nanoparticle solution can
      increase the agglutination reaction of ABO typing. Thus far, the investigation of
      ABO blood group system has been performed using gold nanoparticle solution.
      Samples were tested comparing between with and without gold nanoparticle
      solution. After reading the agglutination reaction, supernatants were collected
      and measured at the optical density at 760 nm by spectrophotometer. The optical
      density of 2-5% cell suspension and monoclonal antibody was higher than in the
      tube of 2-5% cell suspension, monoclonal antibody and gold nanoparticle solution.
      By adding the gold nanoparticle solution, the agglutination reaction was
      increased ranging from 7.0-37.7% (median 15.0%) for ABO grouping system whereas
      12.1-50.9% (median 23.4%) was observed in ABO subgroups. It could decrease the
      chance of misinterpretation by 33.3%. By using gold nanoparticle solution might
      be the alternative way for investigation of weak antigen potency on red blood
      cell.

PMID- 22416585
TI  - Rapid detection of bacteria by carbon quantum dots.
AB  - This work demonstrated a fluorescence measurement method for rapid detection of
      bacteria and their counting by using water-soluble carbon quantum dots (CQDs) as
      a fluorescence marker while sewage water bacteria were detection target bacteria.
      Highly luminescent water-soluble CQDs were prepared by carbonizing waste part of
      rice straw materials in a furnace under in-sufficient air flow. Bacteria in a LB
      media with < 100 nm of water soluble CQDs were cultured for 30-40 minutes. The
      multi colored bacterial cell images were obtained by using fluorescence
      microscopy. Our results showed that CQDs prepared in water phase were highly
      luminescent, stable, and successfully conjugated with bacterial cell membrane
      only. Also we could count the total number of bacteria within a shortest time
      from any sample of environment.

PMID- 22416586
TI  - A perceptually based comparison of image similarity metrics.
AB  - The assessment of how well one image matches another forms a critical component
      both of models of human visual processing and of many image analysis systems. Two
      of the most commonly used norms for quantifying image similarity are L1 and L2,
      which are specific instances of the Minkowski metric. However, there is often not
      a principled reason for selecting one norm over the other. One way to address
      this problem is by examining whether one metric, better than the other, captures
      the perceptual notion of image similarity. This can be used to derive inferences
      regarding similarity criteria the human visual system uses, as well as to
      evaluate and design metrics for use in image-analysis applications. With this
      goal, we examined perceptual preferences for images retrieved on the basis of the
      L1 versus the L2 norm. These images were either small fragments without
      recognizable content, or larger patterns with recognizable content created by
      vector quantization. In both conditions the participants showed a small but
      consistent preference for images matched with the L1 metric. These results
      suggest that, in the domain of natural images of the kind we have used, the L1
      metric may better capture human notions of image similarity.

PMID- 22416587
TI  - Visual judgments of kinship: an alternative perspective.
AB  - Following other researchers, we investigated the premise that visual judgment of
      kinship might be modelled as a signal-detection task, strictly related to similar
      facial features. We measured subjects' response times to face-pair stimuli while
      they performed visual judgments of kinship, similarity, or dissimilarity, and
      examined some priming effects involved. Our results show that kinship judgment
      takes longer on average than either similarity or dissimilarity judgment-which is
      compatible with existing models, yet might also suggest that kinship judgments
      are of a more complex character. In our priming study we observed selective
      suppression/enhancement of the efficacy of dissimilarity judgments whenever they
      followed similarity and kinship judgments. This finding confounds the notion,
      inherent in previous models, of resemblance cues signalling for kinship, since
      similarity and dissimilarity cannot be considered just as opposite concepts, and
      observed priming effects need to be explicitly modelled, including dissimilarity
      cues. To model kinship judgments across faces that are perceived as dissimilar, a
      new framework may be required, perhaps accepting the perspective of a task-driven
      use of the visual cues, modulated by experience and cultural conditioning.

PMID- 22416588
TI  - The role of constant curvature in 2-D contour shape representations.
AB  - In early cortex, visual information is encoded by retinotopic orientation
      selective units. Higher-level representations of abstract properties, such as
      shape, require encodings that are invariant to changes in size, position, and
      orientation. Within the domain of open, 2-D contours, we consider how an
      economical representation that supports viewpoint-invariant shape comparisons can
      be derived from early encodings. We explore the idea that 2-D contour shapes are
      encoded as joined segments of constant curvature. We report three experiments in
      which participants compared sequentially presented 2-D contour shapes comprised
      of constant curvature (CC) or non-constant curvature (NCC) segments. We show
      that, when shapes are compared across viewpoint or for a retention interval of
      1000 ms, performance is better for CC shapes. Similar recognition performance is
      observed for both shape types, however, if they are compared at the same
      viewpoint and the retention interval is reduced to 500 ms. These findings are
      consistent with a symbolic encoding of 2-D contour shapes into CC parts when the
      retention intervals over which shapes must be stored exceed the duration of
      initial, transient, visual representations.

PMID- 22416589
TI  - Agency and control for the integration of a virtual tool into the peripersonal
      space.
AB  - Our representation of the peripersonal space is tied to our representation of our
      bodies. This representation appears to be flexible and it can be updated to
      include the space in which tools work, particularly when the tool is actively
      used. One indicator of this update is the increased efficiency with which sensory
      events near the tool are processed. In the present study we examined the role of
      visuomotor control in extending peripersonal space to a common virtual tool-a
      computer mouse cursor. In particular, after participants were exposed to
      different spatial mappings between movements of the mouse cursor and movements of
      their hand, participants' performance in a motion-onset detection task was
      measured, with the mouse cursor as the stimulus. When participants, during
      exposure, had the ability to move the cursor efficiently and accurately (familiar
      hand-cursor mapping), they detected motion-onset targets more quickly than when
      they could not move the cursor at all during exposure (no hand-cursor mapping).
      Importantly, reversing the spatial correspondence between the movements of the
      hand and the cursor (unfamiliar hand-cursor mapping) during exposure, which was
      thought to preserve the ability to move the cursor (ie agency) while weakening
      the ability to make the movements efficiently and accurately (ie control),
      eliminated the detection-facilitation effect. These results provide evidence for
      the possible extension of peripersonal space to frequently used objects in the
      virtual domain. Importantly, these extensions seem to depend on the participant's
      knowledge of the dynamic spatial mapping between the acting limb and the visible
      virtual tool.

PMID- 22416590
TI  - Reflections on the hand: the use of a mirror highlights the contributions of
      interpreted and retinotopic representations in the rubber-hand illusion.
AB  - In the rubber-hand illusion, observing a rubber hand stroked in synchrony with
      one's own hand results in mislocalisation of the own hand, which is perceived as
      being located closer to the rubber hand. This illusion depends on having the
      rubber hand placed at a plausible egocentric orientation with respect to the
      observer. In the present study, we took advantage of this finding in order to
      compare the relative influence on the illusion of the rubber hand's perceived
      retinotopic image against its real-world position. The rubber hand was positioned
      egocentrically (fingers away from the participant) or allocentrically (fingers
      towards the participant), while participants viewed it either directly or via a
      mirror that was placed facing the participant. In the mirror conditions, the
      orientation of the retinotopic image of the hand (either egocentric or
      allocentric) was opposed to its real-world orientation. We found that the
      illusion was elicited in both mirror conditions, to roughly the same extent. Thus
      either of two representations can elicit the rubber-hand illusion: a world
      centred understanding of the scene, resulting from the inferred position of the
      hand based on its mirror reflection, or a purely visual retinotopic
      representation of the viewed hand. In the mirror conditions, the illusion was
      somewhat weaker than in the typical directly viewed egocentric condition. We
      attribute this to competition between two incompatible representations introduced
      by the presence of the mirror. Finally, in two control experiments we ruled out
      that this reduction was due to two properties of mirror reflections: the
      increased perceived distance of items and the reversal of the apparent handedness
      of the rubber hand.

PMID- 22416591
TI  - Scanning behaviour in natural scenes is influenced by a preceding unrelated
      visual search task.
AB  - Three experiments explored the transference of visual scanning behaviour between
      two unrelated tasks. Participants first viewed letters presented horizontally,
      vertically, or as a random array. They then viewed still images (experiments 1
      and 2) or video clips (experiment 3) of driving scenes, under varying task
      conditions. Despite having no relevance to the driving images, layout of stimuli
      in the letter task influenced scanning behaviour in this subsequent task. In the
      still images, a vertical letter search increased vertical scanning, and in the
      dynamic clips, a horizontal letter search decreased vertical scanning. This
      indicated that (i) models of scanning behaviour should account for the influence
      of a preceding unrelated task; (ii) carry-over is modulated by demand in the
      current task; and (iii) in situations where particular scanning strategies are
      important for primary task performance (eg driving safety), secondary task
      information should be displayed in a manner likely to produce a congruent
      scanning strategy.

PMID- 22416592
TI  - Angle illusion in a straight road.
AB  - We report a new angle illusion observed when viewing a real scene involving a
      straight road. The scene portrays two white lines which outline a traffic lane on
      a road and converge to a vanishing point. In experiment 1, observers estimated
      the angle created by these converging lines in this scene or in its image
      projected onto a screen. Results showed strong underestimation of the angle, ie
      over 50% for observations of both the real scene and its projected image.
      Experiment 2 assessed how depth cues in projected images influence the angle
      illusion. Results showed that this angle illusion disappeared when scene
      information surrounding convergent lines was removed. In addition, the illusion
      was attenuated with projection of an inverted scene image. These findings are
      interpreted in terms of a misadoption of depth information in the processing of
      angle perception in a flat image; in turn, this induces a massive angle illusion.

PMID- 22416593
TI  - Features of the selectivity for contrast polarity in contour integration revealed
      by a novel tilt illusion.
AB  - We studied a novel illusion of tilt inside checkerboards due to the role of
      contrast polarity in contour integration. The preference for binding of oriented
      contours having same contrast polarity, over binding of opposite polarity ones
      (CP rule), has been used to explain several visual illusions. In three
      experiments we investigated how the binding effect is influenced by luminance
      contrast value, relatability of contour elements, and distance among them.
      Experiment 1 showed that the effect was indeed present only when the CP rule was
      satisfied, and found it to be stronger when the luminance contrast values of the
      elements are more similar. In experiment 2 the illusion was reported only with
      relatable edges, and its strength was modulated by the degree of relatability.
      The CP-rule effectiveness, thus, seems to depend on good continuation. The
      intensity of contrast polarity signals propagating from an oriented contour might
      be the less intense, the more its direction deviates from linearity. In
      experiment 3 we estimated the distance threshold and found it to be smaller than
      the one found for other illusions, arising with collinear fragments. This seems
      to show that the reach of the contrast polarity signal inside the association
      field of a contour unit is shorter along non-collinear orientations than along
      collinear ones.

PMID- 22416594
TI  - Six-month-old infants perceive the hollow-face illusion.
AB  - In this study we investigated infants' perception of the hollow-face illusion. 6
      month-old infants were shown a concave mask under monocular and binocular viewing
      conditions and the direction of their reaches toward the mask was recorded.
      Adults typically perceive a concave mask as convex under monocular conditions but
      as concave under binocular conditions, depending on viewing distance. Based on
      previous findings that infants reach preferentially toward the parts of a display
      that are closest to them, we expected that, if infants perceive the hollow-face
      illusion as adults do, they would reach to the center of the mask when viewing it
      monocularly and to the edges when viewing it binocularly. The results were
      consistent with these predictions. Our findings indicated that the infants
      perceived the mask as convex when viewing it with one eye and concave when
      viewing it with two eyes. The results show that 6-month-old infants respond to
      the hollow-face illusion. Our finding suggests that, early in life, the visual
      system uses the constraint, or assumption, that faces are convex when
      interpreting visual input.

PMID- 22416595
TI  - When can an object feel heavier than itself? Perceived heaviness of a wielded
      object depends on grasp position.
AB  - Perceived heaviness is a function of how an object resists being moved, and such
      resistance is determined by object mass and the distribution of that mass
      relative to the wrist. Whereas mass is independent of grasp position on an
      object, distribution of mass relative to the wrist is not. Therefore, perceived
      heaviness should vary with grasp position. Blindfolded participants wielded
      internally weighted cylindrical objects while grasping them at different
      distances from the centre of mass. They rated how heavy each object felt at each
      location relative to a standard object. The results show that objects felt
      heavier as they were grasped farther from the centre of mass, highlighting the
      role of the touch system in controlling movement.

PMID- 22416596
TI  - Look at my poster! Active gaze, preference and memory during a poster session.
AB  - In science, as in advertising, people often present information on a poster, yet
      little is known about attention during a poster session. A mobile eye-tracker was
      used to record participants' gaze during a mock poster session featuring a range
      of academic psychology posters. Participants spent the most time looking at
      introductions and conclusions. Larger posters were looked at for longer, as were
      posters rated more interesting (but not necessarily more aesthetically pleasing).
      Interestingly, gaze did not correlate with memory for poster details or liking,
      suggesting that attracting someone towards your poster may not be enough.

PMID- 22416597
TI  - Narcissistic people cannot be moved easily by visual stimulation.
AB  - We examined the relationship between personality and visually induced self-motion
      perception (latency, duration, and magnitude). A psychological experiment with
      radially expanding patterns that induced self-motion perception along the fore
      and aft axis was conducted, followed by personality assessments. We found that
      all the measures of self-motion perception we examined correlated negatively with
      the degree of narcissistic traits.

PMID- 22416598
TI  - Association for the Advancement of Medical Instrumentation/International
      Organization for Standards: key to perfusion quality management and safety one
      patient at a time.

PMID- 22416600
TI  - Randomized trial of the Terumo Capiox FX05 oxygenator with integral arterial
      filter versus Terumo Capiox Baby RX05 and Terumo Capiox AF02 arterial filter in
      infants undergoing cardiopulmonary bypass.
AB  - The purpose of this clinical trial was to evaluate the effect of the Terumo
      Capiox FX05 oxygenator with integrated arterial filter during cardiopulmonary
      bypass (CPB) compared with the Terumo Capiox RX05 Baby RX and arterial filter on
      inflammatory mediators and blood product utilization. Forty patients weighing
      less than 10 kg who underwent congenital heart surgery utilizing cardiopulmonary
      bypass were randomized into either oxygenator group. The endpoints included
      measuring inflammatory markers at six different time points (preoperative
      baseline, CPB circuit being primed, 15 minutes after CPB initiation, status post
      protamine administration, prior to transport to intensive care unit, and within
      12 to 24 hours post surgery), blood product utilization, extubation time, and
      days until discharge. The inflammatory mediators showed no significant
      differences between oxygenators at any time points. However, looking at the
      inflammatory mediators of both the FX and RX groups combined, a statistically
      significant difference was seen in interleukin (IL)-6 at 12/24 hour post surgery
      (p < .001) versus baseline and all other time points. IL-8 at status post
      protamine (p < .001) and 12/24 hours post surgery (p < .001) demonstrated
      significant differences versus all other time points, and IL-10 at status post
      protamine (p < .001) and prior to leaving the operating room (p < .001) were
      statistically different compared to all other time points. Cardiopulmonary bypass
      stimulates the systemic inflammatory response through various components of the
      extracorporeal system. This investigation did not find significant differences in
      cytokines interferon-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12
      p70, tumor necrosis factor (TNF)-alpha, and TNF-beta when comparing these two
      oxygenators. It is well known that various mechanisms contribute to the levels of
      cytokines circulating in a patient's blood volume and many manipulations
      throughout cardiac surgery have the ability to demonstrate anti-inflammatory
      interventions. Further investigation is needed as to how modification of the
      extracorporeal circuit may minimize increases in inflammatory mediators.
      KEYWORDS: infant, bypass, cytokines, blood, infant perfusion strategy.

PMID- 22416599
TI  - Extracorporeal bioartificial liver for treating acute liver diseases.
AB  - Liver is a vital organ of the human body performing myriad of essential
      functions. Liver-related ailments are often life-threatening and dramatically
      deteriorate the quality of life of patients. Management of acute liver diseases
      requires adequate support of various hepatic functions. Thus far, liver
      transplantation has been proven as the only effective solution for acute liver
      diseases. However, broader application of liver transplantation is limited by
      demand for lifelong immunosuppression, shortage of organ donors, relative high
      morbidity, and high cost. Therefore, research has been focused on attempting to
      develop alternative support systems to treat liver diseases. Earlier attempts
      have been made to use nonbiological therapies based on the use of conventional
      detoxification procedures such as filtration and dialysis. However, the absence
      of liver cells in such techniques reduced the overall survival rate of the
      patients and led to inadequate essential liver-specific functions. As a result,
      there has been growing interest in the development of biological therapy-based
      extracorporeal liver support systems as a bridge to liver transplantation or to
      support the ailing liver. A bioartificial liver support is an extracorporeal
      device through which plasma is circulated over living and functionally active
      hepatocytes packed in a bioreactor with the aim to aid the diseased liver until
      it regenerates or until a suitable graft for transplantation is available. This
      review article gives a brief overview of efficacy of various liver support
      systems that are currently available. Also, the development of advanced liver
      support systems, which has been analyzed for improving the important system
      component such as cell source and other culture and circulation conditions for
      the maintenance of the liver-specific functions, have been described. KEYWORDS:
      liver failure, hepatocytes, liver support devices, bioartificial liver,
      bioreactor.

PMID- 22416601
TI  - The correlation of fluid balance changes during cardiopulmonary bypass to
      mortality in pediatric and congenital heart surgery patients.
AB  - Edema acquired during the perioperative period has long been associated with
      increased mortality. Edema acquired during cardiopulmonary bypass (CPB) may
      contribute to this mortality. The intent of this retrospective study was to test
      the premise that edema in the form of a positive fluid balance change (FBC)
      acquired during CPB correlated to mortality. If so, FBC from the beginning of CPB
      (baseline; FBC = 0) to the end of CPB may need to be monitored, measured, and
      controlled on CPB with the same ardor as blood pressure and pH. This
      retrospective analysis reviewed the FBC of 1540 pediatric and congenital heart
      surgery patients at the end of CPB. Additions and subtractions of fluid to the
      combined patient/CPB circuit were routinely quantified during CPB procedures and
      during periods of modified ultrafiltration (MUF). The primary outcome assessed
      was mortality during hospitalization. The overall mortality of the 1540 patients
      was 5.65% from all causes. Eighty percent (n = 1226, mortality = 4.65%) of the
      patients had a zero or negative FBC immediately after CPB/MUF. Twenty percent (n
      = 314, mortality = 9.55%) had a positive FBC. Positive FBC patients tended to be
      in higher risk categories, weighed more, and had longer pump times (p < .05) with
      an adjusted odds ratio for mortality of 1.73 (1.01-2.96, 95% confidence
      interval). There is a correlation between edema acquired during CPB and increased
      mortality in pediatric and congenital heart surgery patients. The potential
      exists for the perfusionist to optimize the fluid balance changes while on CPB to
      reduce mortality rates.

PMID- 22416602
TI  - The prognostic value of using the duration of acute kidney injury in cardiac
      surgery: an example using two antifibrinolytics.
AB  - Previously, we reported that the addition of duration to the Acute Kidney Injury
      Network (AKIN) definition of acute kidney injury (AKI) is a marker for more
      severe kidney injury and predicts long-term mortality. We aimed to evaluate an
      example of the utility of adding AKI duration to the AKIN definition by comparing
      the historical use of aprotinin with Amicar. In a single-center observational
      study, we followed 4987 consecutive patients undergoing cardiac surgery between
      2002 and 2007 for postsurgery AKI. Patients with a history of hemodialysis were
      excluded. Duration of AKI was calculated by the number of days AKI was present as
      defined by a > or = 0.3 (mg/dL) or a > or = 50% increase in serum creatinine from
      baseline or new onset of acute dialysis. Kaplan-Meier and Cox's proportional
      hazard modeling was conducted to evaluate 5-year mortality. Fifty-three percent
      of patients received Amicar (n = 2333) and 47% received high-dose aprotinin (n =
      2093). Patients receiving aprotinin had evidence of more advanced disease and
      comorbidity and were more likely to develop AKI and have longer durations of AKI
      than Amicar (p < .001): 7.0 +/- 11.5 vs. 3.8 +/- 6.0 days (p < .001). Nearest
      neighbor propensity matching demonstrated aprotinin had significantly worse 5
      year mortality compared with Amicar (relative risk [RR] = 2.09, 95% confidence
      interval [CI] = 1.65-2.65). AKI duration added to the AKIN definition of AKI may
      provide the necessary sensitivity and specificity for evaluating renal outcomes
      in clinical trials.

PMID- 22416603
TI  - Effects of health disparities on survival after neonatal heart surgery: why
      should racial, ethnic, gender, and socioeconomic status be included in the risk
      analysis?
AB  - Health disparities are "differences in the quality of health and health care
      across different populations." Potential disparities associated with race,
      ethnicity, gender, and socioeconomic status should be considered when attempting
      to develop models for survival and neurodevelopmental outcomes in neonates
      undergoing congenital heart surgery. Each of the aforementioned sociodemographic
      factors is related to postsurgical mortality because they are frequently linked
      to measures of access to care in addition to location of care (geographically)
      and the type of institution (teaching vs. nonteaching) where patients receive
      care. Traditionally these factors have not been considered in models of surgical
      treatment outcomes in conditions such as hypoplastic left heart syndrome.
      However, we believe these factors should at least be included in risk analysis
      models to help explain their impact on outcomes and in predicting outcomes.
      Therefore, the purpose of this article is to highlight some of the nonsurgical
      influences that affect survival after neonatal heart surgery such as race,
      ethnicity, gender, and socioeconomic status.

PMID- 22416604
TI  - Neonatal extracorporeal membrane oxygenation devices, techniques and team roles:
      2011 survey results of the United States' Extracorporeal Life Support
      Organization centers.
AB  - In early 2011, surveys of active Extracorporeal Life Support Organization (ELSO)
      centers within the United States were conducted by electronic mail regarding
      neonatal Extracorporeal Membrane Oxygenation (ECMO) equipment and professional
      staff. Seventy-four of 111 (67%) U.S. centers listed in the ELSO directory as
      neonatal centers responded to the survey. Of the responding centers, 53%
      routinely used roller pumps for neonatal ECMO, 15% reported using centrifugal
      pumps and 32% reported using a combination of both. Of the centers using
      centrifugal pumps, 51% reported that they do not use a compliance bladder in the
      circuit. The majority (95%) of roller pump users reported using a compliance
      bladder and 97% reported using Tygon" S-97-E tubing in the raceway of their ECMO
      circuits. Silicone membrane oxygenators were reportedly used by 25% of the
      respondents, 5% reported using micro-porous hollow fiber oxygenators (MPHF), 70%
      reported using polymethylpentene (PMP) hollow fiber oxygenators and 5% reported
      using a combination of the different types. Some form of in-line blood monitoring
      was used by 88% of the responding centers and 63% of responding centers reported
      using a circuit surface coating. Anticoagulation monitoring via the activated
      clotting time (ACT) was reported by 100% of the reporting centers. The use of
      extracorporeal cardiopulmonary resuscitation (ECPR) was reported by 53% of the
      responding centers with 82% of those centers using a crystalloid primed circuit
      to initiate ECPR. A cooling protocol was used by 77% of the centers which have an
      ECPR program. When these data are compared with surveys from 2002 and 2008 it
      shows that the use of silicone membrane oxygenators continues to decline, the use
      of centrifugal pumps continues to increase and ECMO personnel continues to be
      comprised of multidisciplinary groups of dedicated allied health care
      professionals.

PMID- 22416605
TI  - Simultaneous individually controlled upper and lower body perfusion for valve
      sparing root and total aortic arch replacement: a case study.
AB  - Optimal perfusion strategies for extensive aortic resection in patients with mega
      aortic syndromes include: tailored myocardial preservation, antegrade cerebral
      perfusion, controlled hypothermia and selective organ perfusion. Typically, the
      aortic arch resection and elephant trunk procedure are performed under
      hypothermic circulatory arrest with myocardial and cerebral protection. However,
      mesenteric and systemic ischemia occur during circulatory arrest and commonly
      rely upon deep hypothermia alone for metabolic protection. We hypothesized that
      simultaneously controlled mesenteric and systemic perfusion can attenuate some of
      the metabolic debt accrued during circulatory arrest, which may help improve
      perioperative outcomes. The perfusion strategy consisted of delivering a 1 to 3
      liter per minute flow at 25 degrees C to the head/upper body via right axillary
      graft and simultaneous perfusion to the lower body/ mesenteric organs of 1 to 3
      liters per minute at 30 degrees C via a right femoral arterial graft. We describe
      our technique of simultaneous mesenteric, systemic, cerebral and myocardial
      perfusion, and protection utilized for a young male patient with Marfan's
      syndrome, while undergoing a valve sparing root replacement, total arch
      replacement and elephant trunk reconstruction. This perfusion technique allowed
      us to deliver differential flow rates and temperatures to the upper and lower
      body (cold head/warm lower body perfusion) to minimize ischemic debt and quickly
      reverse metabolic derangements.

PMID- 22416606
TI  - Hypothermic cardiac arrest in the homeless: what can we do?
AB  - Accidental deep hypothermia with body temperature < 28 degrees C induces high
      mortality rates for neurological and cardiac complications. Although several
      reports described successful treatment of hypothermic arrest by extracorporeal
      membrane oxygenation (ECMO), the field of warming in the homeless is almost
      completely unquestioned although the malnutrition and the co-morbidities are
      usually believed as relevant risk factors for poor outcome. This article
      describes the experience of successful warming by ECMO in two homeless victims of
      unwitnessed cardiac arrest, who survived without neurological or cardiac
      complications. In conclusion, this is an initial experience and further research
      is required, although our results are appreciable in this high risk subset of
      population.

PMID- 22416607
TI  - Stage 1 palliation for hypoplastic left heart syndrome without the use of
      allogeneic tissue, with reduced allogeneic blood product exposure: a case report.
AB  - In the 30 years since Norwood described the palliative procedure for hypoplastic
      left heart syndrome (HLHS), many modifications have been described which have
      increased the survival rate of children born with this lesion. We describe
      further modifications which result in reduced cardiopulmonary bypass time, no
      cooling or circulatory arrest time, and decreased banked blood exposure. A 16-day
      old infant with HLHS undiagnosed during pregnancy presented for stage 1
      palliation incorporating the Mee modification, Sano right ventricle to pulmonary
      artery conduit, dual arterial cannulation of the innominate artery and descending
      aorta, single venous cannulation of the right atrium, and a bypass prime volume
      of 130 mL. Anticoagulation and hemostasis were monitored with the Hepcon HMS Plus
      Hemostasis Management System (Medtronic USA, Minneapolis, MN). Bypass commenced
      at normothermia. A 5.0 Gore-Tex shunt was placed for the Sano Shunt, and the
      aortic arch was repaired without use of homologous tissue or synthetic material
      using a modification of the Mee technique. Bypass time was 92 minutes with a 10
      minutes cardiac ischemic time. Modified ultrafiltration (MUF) was performed for
      12 minutes and heparinization was reversed with protamine. There was no
      significant bleeding and no indication to transfuse clotting factors. The
      patient's only allogeneic donor exposure was 350 mL of red blood cells during
      bypass necessary to achieve a post MUF hematocrit of 50% per our current
      institution policy for cyanotic infants. Using modified surgical and perfusion
      techniques along with low prime bypass circuits can result in reduced cross clamp
      and bypass times as well as a decrease in blood donor exposure. Hypothetical
      benefits include reduced operating room, ventilation, intensive care unit, and
      hospital times, improved neurodevelopmental outcomes, and an overall reduction in
      the cost of care for infants with HLHS.

PMID- 22416608
TI  - Technical description of the use of selective perfusion techniques during the
      Norwood procedure for hypoplastic left heart syndrome.
AB  - Since the introduction of the Norwood procedure for surgical palliation of
      hypoplastic left heart syndrome in 1983, refinements have been made to the
      original procedure to improve patient outcomes while still accomplishing the
      original goals of the procedure. One of these refinements has been the
      introduction of regional selective perfusion to limit the duration of circulatory
      arrest times and optimize the regional flow distribution. In this paper we
      describe our technique for performing selective cerebral and lower body perfusion
      during the Norwood procedure.

PMID- 22416609
TI  - The addition of a membrane oxygenator to a ventricular assist device in a patient
      with acute respiratory distress syndrome.
AB  - A 12-year-old boy with Marfan's syndrome required a biventricular assist device
      (VAD) after an aortic root replacement. The patient developed acute respiratory
      distress syndrome and required escalating ventilator support. We hypothesized
      that the addition of a membrane oxygenator in series with the assist device would
      improve gas exchange and allow for a more lung-protective ventilator approach. A
      membrane oxygenator was placed in series with the right VAD resulting in a blood
      path of right atrium to VAD to oxygenator to pulmonary artery. Circuit function
      was gauged by monitoring flow and oxygenator pressures and periodic circuit
      inspections and oxygenator blood gases. Heparin was titrated to maintain
      unfractionated antifactor Xa levels of .3-.7 IU/mL and partial thromboplastin
      time of 60-80 seconds. The initial sweep gas supplying the oxygenator was 5 L/min
      at an F1O2 of 1.0, which achieved a pH > 7.40 and a PF ratio > 250. The pre- and
      post-oxygenator pressures were 55-60 mmHg and 45-50 mmHg, respectively, and the
      measured flow at the oxygenator outlet was 2.0-2.2 L/min. The patient was changed
      from high-frequency oscillatory ventilation to pressure-controlled synchronized
      intermittent ventilation with pH maintained at 7.35-7.40 and PF ratio > 250.
      Paralytics were discontinued and the patient's neurologic condition was deemed
      intact. The patient hemorrhaged after a sternal closure and required transfusions
      and antifibrinolytics that led to thrombus in the membrane and membrane
      circuitry, which were replaced without incident. The patient's respiratory status
      remained stable; however, his overall condition worsened as a result of
      additional organ dysfunction and septicemia, and he did not survive. The addition
      of a membrane oxygenator to a VAD is feasible and supplements gas exchange
      permitting the use of more lung protective ventilation.

PMID- 22416610
TI  - Lessons in shifing the burden: #2. Competence to practice.

PMID- 22416611
TI  - Dentistry is at a tippinq point--we need your hand.

PMID- 22416612
TI  - Optimism is part of the cure.

PMID- 22416613
TI  - Personal ethical dilemma: is the patient competent?

PMID- 22416614
TI  - Putting your money where your mouth is: the influence of American consumer
      culture on contemporary dentistry.

PMID- 22416615
TI  - Can we change?

PMID- 22416616
TI  - Comprehension and retention of orthodontic and orthognathic surgery treatment
      information: a review of literature.

PMID- 22416617
TI  - The ethics of routine use of advanced diagnostic technology.

PMID- 22416618
TI  - Retention of underrepresented minority students in dental school: one dental
      schools story.
AB  - There is a large disparity between the proportions of African-Americans,
      Hispanics, and Native Americans in the general population and in the dental
      profession. While these underrepresented minorities (URMs) as a group make up
      almost 30% of the United States population, they constitute only about 6% of the
      nation's dentists. Eliminating this disparity is important in addressing access
      to care for underrepresented groups. Texas A&M Health Science Center Baylor
      College of Dentistry (TAMHSC-BCD) enrolled greater numbers and proportions of URM
      students than any other non-minority school from 2006-2010. Strategies used to
      achieve this level of diversity include a Whole File Review process; career
      awareness activities for elementary, junior high and high school students; and
      academic enrichment programs for college students and college graduates.
      Retaining and graduating URM students is just as important as enrolling them.
      TAMHSC-BCD's retention rate over the last five years is 95.7% for all students
      and 92.5% for URM students. A wide range of services aids in the retention
      process. These services are available to all students and include monitoring of
      students' academic performance followed up with academic advisement as
      appropriate, peer tutoring, an alternative five-year curriculum, professional
      psychological counseling, professional learning assessments, social support; and
      mentoring through student organizations. The retention program at TAMHSC-BCD can
      serve as a model for other dental and other health professions schools seeking
      ways to ensure the academic success of their URM students. The more of these
      students we enroll and graduate, the more the problem of access to dental care is
      addressed.

PMID- 22416619
TI  - The case of the pregnant adolescent.
AB  - In this case an adolescent, minor female presents herself for routine dental
      care, but is pregnant without parental knowledge. She asks the dentist not to
      reveal the pregnancy to her parents. Three experts including one attorney, one
      dental educator with 25 years of private practice experience, and one member of a
      state psychological association's ethics committee comment on the difficult
      ethical and legal issues found in this actual case.

PMID- 22416620
TI  - How to make moral choices.
AB  - Moral choice is committing to act for what one believes is right and good. It is
      less about what we know than about defining who we are. Three cases typical of
      those used in the principles or dilemmas approach to teaching ethics are
      presented. But they are analyzed using an alternative approach based on seven
      moral choice heuristics--approaches proven to increase the likelihood of locating
      the best course of action. The approaches suggested for analyzing moral choice
      situations include: (a) identify the outcomes of available alternative courses of
      action; (b) rule out strategies that involve deception, coercion, reneging on
      promises, collusion, and contempt for others; (c) be authentic (do not deceive
      yourself); (d) relate to others on a human basis; (e) downplay rational
      justifications; (f) match the solution to the problem, not the other way around;
      (g) execute on the best solution, do not hold out for the perfect one; and (h)
      take action to improve the choice after it has been made.

PMID- 22416622
TI  - Effectiveness of a vegetable dental chew on periodontal disease parameters in toy
      breed dogs.
AB  - Sixteen toy breed dogs completed a parallel, 70-day two-period, cross-over design
      clinical study to determine the effect of a vegetable dental chew on gingivitis,
      halitosis, plaque, and calculus accumulations. The dogs were randomly assigned
      into two groups. During one study period the dogs were fed a non-dental dry diet
      only and during the second study period were fed the same dry diet supplemented
      by the daily addition of a vegetable dental chew. Daily administration of the
      dental chew was shown to reduce halitosis, as well as, significantly reduce
      gingivitis, plaque and calculus accumulation and therefore may play a significant
      role in the improvement of canine oral health over the long-term.

PMID- 22416621
TI  - Canine periodontal disease control using a clindamycin hydrochloride gel.
AB  - Stabilizing or reducing periodontal pocket depth can have a positive influence on
      the retention of teeth in dogs. A topical 2% clindamycin hydrochloride gel
      (CHgel) was evaluated for the treatment of periodontal disease in dogs. The CHgel
      formulation provides for the sustained erosion of the matrix, but also flows into
      the periodontal pocket as a viscous liquid, and then rapidly forms a gel that has
      mucoadhesive properties and also may function as a physical barrier to the
      introduction of bacteria. A professional teeth cleaning procedure including
      scaling and root planing was done in dogs with one group receiving CHgel
      following treatment. Periodontal health was determined before and after the
      procedure including measurement of periodontal pocket depth, gingival index,
      gingival bleeding sites, and number of suppurating sites. There was a
      statistically significant decrease in periodontal pocket depth (19%), gingival
      index (16%), and the number of bleeding sites (64%) at 90-days in dogs receiving
      CHgel. Additionally, the number of suppurating sites was lower (93%) at 90-days
      for the group receiving CHgel. The addition of CHgel effectively controlled the
      bacterial burden (e.g, Fusobacterium nucleatum) at both day 14 and 90. Gingival
      cells in culture were shown to rapidly incorporate clindamycin and attain
      saturation in approximately 20-minutes. In summary, a professional teeth cleaning
      procedure including root planning and the addition of CHgel improves the gingival
      index and reduces periodontal pocket depth.

PMID- 22416623
TI  - Comparison of shear bonding strength for two different etching systems in canine
      and human dentin.
AB  - Canine dentin has increased size and number of dentinal tubules compared to human
      dentin. With less intertubular surface area for bonding to composite material in
      dog teeth, bonding shear strength may be affected negatively. This study was
      designed to compare the shear bonding strength of canine and human dentin. It
      also compared bond strength of two different acid etch systems when used with the
      same composite resin. The shear bond strength of composite cylinders to dentin
      was measured in 30 extracted canine cuspid teeth and a similar number of human
      molar teeth. Shear bond strength was 40% greater for human compared with canine
      dentin. This significantly different (P < 0.05) result validates the hypothesis
      that dentin bond strength is positively correlated with the area of intertubular
      dentin. Results also indicated that shear bond strength was greater in the self
      etching bond system compared with the etch and rinse system, although this
      difference was not significant.

PMID- 22416624
TI  - Acquired myasthenia gravis associated with oral sarcoma in a dog.
AB  - Acquired myasthenia gravis is a common neuromuscular disorder resulting from
      autoantibody directed against the post-synaptic acetylcholine nicotinic receptors
      in skeletal muscle. Myasthenia gravis has been reported previously as a
      paraneoplastic syndrome. This case report presents myasthenia gravis secondary to
      an oral sarcoma in a juvenile Mastiffdog.

PMID- 22416625
TI  - Unilateral mandibular hyperostosis in a cat.

PMID- 22416626
TI  - Bisphosphonate related osteonecrosis of the jaws: a review.
AB  - Bisphosphonate use has increased in veterinary medicine over the last decade.
      During this time, bisphosphonate related osteonecrosis of the jaws (BRONJ) in
      human patients has been identified. Only recently was a dog model for BRONJ
      developed for human oral surgery and medicine. Veterinary patients treated with
      bisphosphonates may be at an increased risk for BRONJ There has been little, to
      no, investigation of potential long term side-effects of bisphosphonate use in
      veterinary patients; potential sequelae are unknown. The history of
      bisphosphonates, their use, and BRONJ in veterinary patients are discussed.

PMID- 22416627
TI  - Guided tissue regeneration for infrabony pocket treatment in dogs.

PMID- 22416628
TI  - Dental school debt: swimming to the surface or drowning.

PMID- 22416629
TI  - Muda ethics.

PMID- 22416630
TI  - More plans needed for treating cleft-palate patients during chaotic times.

PMID- 22416631
TI  - Dental sleep medicine.

PMID- 22416632
TI  - Somnology 101: a primer on sleep disorders, their impact on society, and a role
      for dentistry.
AB  - Sleep is necessary for our existence. It is one-third of a commitment to health
      along with nutrition and exercise. While we spend one-third of our lives asleep,
      studies show one-third of the U.S. population suffers with a significant sleep
      disorder at some point in their lifetime. This manuscript introduces sleep and
      sleep disorders, focuses on those sleep disorders within the domain of dentistry,
      and addresses contributions the dental community can make toward specific sleep
      problems.

PMID- 22416633
TI  - Medical consequences and associations with untreated sleep-related breathing
      disorders and outcomes of treatments.
AB  - Sleep-related breathing disorders are a broad group of disorders that include
      obstructive sleep apnea, central sleep apnea, and periodic breathing disorders.
      This article reviews the scientific literature that links SRBD to various medical
      conditions including hypertension, coronary artery disease, cardiac arrhythmias,
      stroke, diabetes mellitus, obesity, and depression. Pathophysiologic mechanisms
      by which SRBD may contribute to these disorders will be discussed, as will data
      on the degree to which treatment of SRBD may improve these conditions.

PMID- 22416634
TI  - Past, present, and future use of oral appliance therapies in sleep-related
      breathing disorders.
AB  - Upper airway patency is a delicate balancing act pitting pharyngeal anatomy and
      baseline muscle tone against the negative pressures created upon inhalation. This
      uniquely human phenomenon has created for some patients the need for upper airway
      management during sleep. In this regard, the ability of removable oral appliances
      utilized during sleep to create and maintain a patent airway has seen the
      creation of a new area of interest in dentistry termed dental sleep medicine.

PMID- 22416635
TI  - Neurology of sleep and sleep-related breathing disorders and their relationships
      to sleep bruxism.
AB  - Conditions that affect sleep can impact overall health. More than 70 million
      Americans suffer from problems with sleep. The purpose of this article is to
      provide the basic science of sleep physiology and how it relates to disorders
      that are pertinent to dentistry. Concepts are presented that explain airway
      dynamics and how the jaw and tongue influence airway obstruction. Additionally,
      explanation is given on an association between temporomandibularj aw dysfunction
      and bruxism during sleep.

PMID- 22416636
TI  - Dentistry-based approaches to sleep-disordered breathing, algorithms, and
      multidisciplinary perspectives.
AB  - Sleep disorders affect more than 20 percent of the U.S. population, but less than
      7 percent have been medically diagnosed. Dentists are ideally positioned to
      identify many patients who fall under the grouping of sleep-disordered breathing.
      This paper presents perspectives on sleep-related issues from various medical
      specialties with a goal to broaden the dentist's appreciation of this topic and
      open avenues of communication. Algorithms are proposed to guide dentists
      following positive screenings for sleep-disordered breathing.

PMID- 22416637
TI  - Salt: there's Na-thing like it.

PMID- 22416638
TI  - Proceedings of the first UNIBADAN Conference of Biomedical Research.

PMID- 22416639
TI  - Industrialization and the increasing risk of genome instability in developing
      countries: nutrigenomics as a promising antidote.
AB  - Increased reliance on chemicals in the industrializing developing countries
      places new demands on them, as they have limited resources to adequately regulate
      exposure to these chemicals. Majority of the chemicals cause mutation in DNA
      among others. The consequences of increased exposure to chemicals on the genome
      and their mitigation by Nutrigenomics, a science concerned with the prevention of
      genome damage by nutritional factors is poorly recognized in these countries.
      Growing evidence indicates that genome instability in the absence of overt
      exposure to genotoxicants is a sensitive marker of nutritional deficiency.
      Therefore, the increasing prevalence of chemicals in these countries which
      contribute to genome disturbances and the widespread nutritional deficiency, at
      least double the risk of genome instability.Environmental pollutants such
      polychlorobiphenyls, metal fumes, and fly ash, common in these countries are
      known to increase urinary level of 8-hydroxy deoxyguanosine (8-OHdG), a marker of
      oxidative DNA damage, precursor of genome instability.Increasing evidence
      emphasizes the importance of zinc in both genetic stability and function. Zinc
      deficiency has been linked with oxidative stress, DNA damage and impairment of
      repair mechanisms as well as risk of cancer. Zinc plays an important role in
      vitamin A metabolism from which the retinoids are derived. Zinc is also an
      important component of the p53 protein, a DNA damage sensor which prevents
      genetic lesions contributing to genome instability.Zinc deficiency ranks among
      the top 10 leading causes of death in developing countries. A large proportion of
      the population in these countries ingests less than 50% of the RDA for Zn.This
      makes this genome protective nutrient among others grossly inadequate. Folate now
      also recognized for its role in genome stability, is among the nutrients
      frequently cited as critical to genome stability. Folate deficiency of sub-
      clinical degree is common. Reduced folate intake causes as much genome damage as
      that induced by exposure to a high dose of ionizing radiation. Even moderate
      folate deficiency causes very severe damage to the genome in the general
      population. All these accentuate the susceptibility of populations in these
      nations to environmental toxic assault requiring preventive measures employing
      the science of Nutrigenomics, probably augmented with adaptive response pathways
      such as the Nrf2 signaling pathway. Human populations in developing countries are
      increasingly exposed to a diverse array of industrial chemicals, which adversely
      modify the genome, the precursor of many diseases especially cancer.
      Nutrigenomics encompasses nutritional factors that protect the genome from damage
      and is a promising new field that can be exploited, perhaps augmented with the
      Nrf2 signaling pathway with international collaboration in these nations as an
      antidote to chemical-induced genome instability.

PMID- 22416640
TI  - Biological characterization of Nigerian chicken anaemia virus isolates.
AB  - Chicken anaemia virus (CAV) DNA was extracted from thymus, liver and bone marrow
      samples obtained from broiler and pullet chicken flocks in southwestern Nigeria,
      which presented with clinical signs and lesions suggestive of both infectious
      bursal disease and chicken infectious anaemia. While CAV was successfully
      isolated in MDCC-MSB1 cells from four of the pooled tissue samples, the remaining
      two samples failed to grow in cells. Monoclonal antibody (MAb) characterization
      using four MAbs produced against the reference Cuxhaven-1 (Cux-1) CAV isolate
      showed that Nigerian CAV isolates are antigenically related to each other and to
      the Cux-1 virus. Pathogenicity studies with the Cux-1 virus and one of the
      Nigerian isolates (NGR-1) revealed that NGR-1 was more pathogenic that the
      former. We conclude that although Nigerian CAV isolates are antigenically related
      to each other, they differ in terms of cell culture growth characteristics and
      probably pathogenicity. These findings further confirm that CAV exists and can no
      longer be ignored in poultry disease diagnosis in Nigeria. Cases hitherto
      diagnosed as IBD may actually be CIA or a co-infection of the two.

PMID- 22416642
TI  - Biomedical instruments: safety, quality control, maintenance, prospects and
      benefits of African technology.
AB  - Biomedical instruments are fundamental to successful medical practice. Medical
      instruments are devices intended to diagnose, treat, or monitor the patient under
      medical supervision. Such devices make physical or electrical contact with the
      patient and/or transfer energy to or from the patient and/or detect such energy
      transfer to or from the patient. These devices are imported to Africa from
      developed countries. They are operated in tropical African hospitals where as
      they were designed for more temperate environment. African countries pay high
      prices for these devices. The result is that these devices are not available in
      most African hospitals. Patients have to travel to the major cities to benefit
      from such devices.These devices must be properly installed in an environment in
      which they can give accurate and uninterrupted service. Proper operation, regular
      care and maintenance of these devices are essential. The consequences of
      breakdown of biomedical instruments include unusable equipment, untreated
      patients, wrong diagnosis, wrong treatment, frustrated medical staff and
      overloaded repair shops. The important interwoven issues of safety, quality
      control and maintenance are discussed. To achieve the millennium development goal
      of health for all, it is necessary to increase the availability of these devices
      in Africa. The prospects and benefits of manufacturing and or assembling these
      devices in Africa are discussed. Can the Engineering Faculties and Industries in
      Africa meet this challenge? The answer is 'yes'! The design and construction of
      Bedside Monitor by four Electrical/Electronic Engineering Undergraduates of the
      University of Ibadan, Ibadan, Nigeria is presented as a case study.

PMID- 22416641
TI  - Hepatoprotective effect of Curcuma longa L. in D-galactosamine induced liver
      injury in mice: evidence of antioxidant activity.
AB  - The aim of this study was to investigate the hepatoprotective effect of
      methanolic extract of Curcuma longa L (CLME) in D-galactosamine (GNH2) induced
      liver injury and the mechanism(s) involved. The ability of vitamin C (VC) to
      attenuate the toxicity was also examined. Mice were pretreated with CLME and VC
      at a dose of 100-mg/kg per oral for seven consecutive days before challenge with
      a dose of GNH2 (800 mg/kg i.p.). Integrity of liver from the animals was assessed
      by determining the levels of serum alanine and aspartate aminotransferases (ALT
      and AST) and alkaline phosphatase (ALP). The antioxidant status was monitored by
      the levels of hepatic superoxide dismutase (SOD), catalase (CAT), glutathione-s
      transferase (GST), glutathione (GSH) and malondialdehyde (MDA) (Lipid
      peroxidation (LPO) index). GNH2 treatment markedly increased the levels of serum
      ALT and AST, which were significantly (p<0.05) attenuated in animals pretreated
      with CLME and VC. Also, CLME significantly (p<0.05) increased the levels of
      hepatic GST and SOD, with a concomitant marked reduction in the levels of hepatic
      and serum LPO in the GNH2-challenged mice. Furthermore, hepatic GSH which was
      decreased after GNH2 intoxication, was significantly (p<0.05) enhanced by
      cotreatment with CLME and VC. However, there were no significant differences
      (p>0.05) in the levels ofALP and CAT of these animals. The liver histopathology
      results revealed that GNH2-induced injury was prevented in mice co-treated with
      VC and CLME. The results suggest that the hepatoprotective effect of CLME in GNH2
      induced liver injury may be related to its antioxidant activity.

PMID- 22416644
TI  - Effects of the leaf decoction of Momordica charantia (bitter melon) on
      Mitochondrial Membrane Permeability Transition Pore (MMPTP) and fertility in
      normal male albino rats.
AB  - Momordica charantia (M. charantia), a medicinal plant of the family,
      Cucurbitaceae, is used in treating an array of ailments including diabetes,
      heamorrhoids, fevers and various cancers. Programmed cell death may be modulated
      by an intrinsic pathway involving the release of cytochrome C when the
      mitochondrial membrane permeability transition (MMPTP) pore is opened. Opening of
      MMPT pore was assayed using the method of Lapidus and Sokolove. The results
      obtained revealed that there was a dose-dependent and significant increase in the
      opening of the MMPT pore in rats orally administered the decoction with maximum
      induction (11-fold increase) at 55mg/100g body weight (bw), although the extent
      of opening of the pore was reduced at 65mg/100g bw (9-fold increase). An
      assessment of the blood parameters of animals orally exposed to the decoction
      showed significant decrease (p<0.05) in lymphocytes and a significant increase
      (p<0.05) in neutrophils at 55mg/ 100g bw. Moreover, significant increases
      (p<0.05) in RBC levels at 45 and 65mg/100g bw, were observed. Similarly, PCV and
      Heamoglobin values were also elevated at 65mg/100g bw while there was a
      significant reduction (p<0.05) in MCV and MCH values at 45, 55 and 65mg/100g bw.
      MCHC values were reduced only in animals that received 65mg/ 100g when compared
      to control animals. Analysis of the spermiogram of the experimental rats showed
      significant reductions (p<0.05) in sperm motility and sperm cell concentrations
      for all animals that were orally exposed to the decoction. There was a
      significant reduction (p<0.05) in percentage viability in animals that received
      45mg/100g bw and above. Morphological abnormalities of sperm cells above the
      proposed percentage range (10%) were also observed in animals that received
      45mg/100g bw and above. However, decoction did not show any significant effect on
      ALT and AST levels but there were significant increases (p<0.05) in a somewhat
      dose-dependent pattern in ALP and aGT levels for all groups in comparison to the
      control group. These findings thus suggest dose-related negative or toxic effects
      of sub acute (30-day) oral administration of leaf decoction of M. charantia in
      albino rats and may therefore pose some danger to humans especially in regard to
      male fertility in individuals who rely on oral administration of the decoction in
      treating various ailments.

PMID- 22416643
TI  - Anti-inflammatory activities of a kolaviron-inhibition of nitric oxide,
      prostaglandin E2 and tumor necrosis factor-alpha production in activated
      macrophage-like cell line.
AB  - Kolaviron (KV), a biflavonoid fraction from the seeds of Garcinia kola has been
      shown to posess antiinflammatory properties in animal models of inflammation. In
      this study, the effect of KV on carrageenan-induced paw edema was investigated in
      mice. Furthermore, the effects of KV on the production of the pro-inflammatory
      mediators- nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) were
      examined in an activated macrophage-like cell lines, RAW 264.7 cells.
      Administration of KV prior to injection of carrageenan significantly reduced the
      paw inflammation in a dose-dependent manner. KV consistently inhibited in-vitro
      production of NO and secretion of TNF-alpha in a dose-dependent manner. In
      addition, KV reduced the production of PGE2 in LPS-stimulated macrophages.
      Viability of cells at all concentrations studied was unaffected as determined MTT
      [3-(4,5- dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide] cytotoxicity
      assay. These results suggest that KV has inhibitory effects on LPS-induced TNF
      alpha, NO and PGE2 production.

PMID- 22416645
TI  - Anti-psychotic and sedative effect of calcium channel blockers in mice.
AB  - Calcium channel blockers (CCBs) are widely used as therapeutic agents, for the
      treatment of cardiovascular disorders. However, the discovery that CCBs bind to
      various regions of the brain suggest that they might also offer some beneficial
      effects in the treatment of neuropsychiatry disorders. This study was carried out
      to evaluate the anti-psychotic and sedative effects of two notable calcium
      channel blockers, verapamil and nifedipine in mice. The anti-psychotic effects of
      the CCBs were studied in the animal model of amphetamine-induced stereotyped
      behavioral disorders. The sedative effect was assessed utilizing the prolongation
      of the time of sleep, induced by thiopentone. The ability of CCBs to produce
      catalepsy in mice was also evaluated in the study. Graded doses of verapamil (5.0
      20.0 mg/kg, i.p) significantly (p<0.05) suppressed stereotyped behaviour induced
      by amphetamine (10.0 mg/kg, i.p). In contrast, nifedipine (5.0-20.0 mg/kg, i.p)
      did not exhibit anti-psychotic effect, as it could not significantly reduce
      stereotypy caused by amphetamine. In the test for sedation, both verapamil (5.0
      20.0 mg/kg, i.p) and nifedipine (10.0-20.0 mg/kg) significantly (p<0.05)
      prolonged the sleeping time induced by thiopentone (50.0 mg/kg, i.p). However,
      neither verapamil (5.0-20.0 mg/kg, i.p.) nor nifedipine (5.0-20.0 mg/kg, i.p.) at
      the tested doses produced any cataleptic behaviour in the animals. The results of
      the study suggest that verapamil has both anti-psychotic and sedative effects
      without inducing the side effect of catalepsy and might be relevant in the
      treatment of psychosis.

PMID- 22416646
TI  - Evaluation of antioxidant properties of Mallotus oppositifolium in in-vitro, in
      vivo and ex-vivo model systems.
AB  - The protective effect of antioxidants and naturally occurring substances against
      oxidative stress damage has recently attracted much attention. The leaves of
      Mallotus oppositifolium, a shrub of the family Euphorbiacea that grows in many
      parts of Africa, are used in folk medicine and herbal preparations for the
      treatment of dysentery, worms and malaria. The study investigated the antioxidant
      properties of the methanolic extract of the leaves of Mallotus oppositifolium
      (MEMO) in comparison with butylated hydroxyl anisole (BHA) as a standard
      antioxidant using three free radical generators viz hydrophilic radical generator
      2,2-azobis(2-amidino propane) dihydrochloride (AAPH), hydrophobic radical
      generator 2,2-azobis(2,4-dimethylvaleronitrile) (AMVN) and hydroxyl radical and
      non-specific radical generator Fe2+/ascorbate system in an in vitro, in vivo and
      ex-vivo model systems. Phytochemical analysis of the leaves extract was also
      assessed. Phytochemical analysis of the powdered leaves revealed the presence of
      alkaloids, tannins, cardenolides and saponins. In vitro study indicated that
      while MEMO failed to inhibit lipid peroxidation (LPO) induced by AAPH, while BHA
      offered 55.5% inhibition. In addition, while AMVN-induced LPO was inhibited by
      17.7% and 29.4% by MEMO and BHA respectively, Fe2+/ascorbate system-induced LPO
      was inhibited by 57.9% and 78.9% by MEMO and BHArespectively. Ex-vivo studies
      showed that MEMO at 100mg/kg bw reduced malondialdehyde and protein carbonyl
      levels by 34.5% and 12.0% respectively compared with the control. In vivo, MEMO
      increased (P<0.05) superoxide dismutase and catalase activities by 408.0% and
      295.0% respectively. Taken together, this study demonstrates that MEMO exhibits
      antioxidant, radical scavenging and enhancement of enzymatic antioxidant capacity
      and as such could intervene in toxicological processes mediated by free radical
      mechanisms.

PMID- 22416647
TI  - Mathematical modeling of the epidemiology and the transmission dynamics of
      HIV/AIDS infections in Nigeria.
AB  - Many of the already proposed models for the transmission of HIV/AIDS do not fit
      the situations in Nigeria. This is in part due to the fact that many of the
      models pay more attention to either homogeneity of sexual contact or population
      of homosexuals. Although some notable models have also been studied by different
      authors in times and places for heterosexual transmission of HIV/AIDS epidemics,
      none of these models addressed the peculiar transmission dynamics in Nigeria. In
      this study, we grouped the population into susceptible, infected and AIDS men and
      women with sexual contact as the major route for HIV transmission. Assuming a
      strong sexual network between the groups and with the AIDS group unable to
      contribute to infection, we formulated mathematical models for the heterosexual
      transmission dynamics of HIV/AIDS in Nigeria. Our models incorporated parameters
      and variables that describe the nature and the strength of the transmission
      across the groups. We also presented model predictions on pattern of mixing
      between and within the groups and how these in turn determine the global dynamics
      of the epidemics in Nigeria. Our simulation results show that, an increase in the
      transmission probability as well as in the number of sexual partnership poses
      more treat to the population than other parameters. The model predictions show
      that the epidemics tend to level up after year 2010. The number of sexual
      partners change per year and the probability of an effective contact are among
      the most critical variables in the HIV/AIDS epidemics in a community of
      heterosexual Nigerians. Our results agree with recent findings of similar models
      for some Sub-Saharan African countries. Also, results from the predictions based
      on the most recent National HIV Seroprevalence Surveillance Survey conducted in
      Nigeria agree with our findings.

PMID- 22416648
TI  - Influence of quercetin on haematological indices and biomarkers of oxidative
      stress in the serum of rats exposed to atrazine.
AB  - The study was carried out to compare the effects of quercetin (QT) at doses of
      5mg/kg (Q5) and 10mg/kg (Q10) against the hematological toxicity and oxidative
      stress caused by atrazine (ATR). Male rats were orally gavaged with ATR at a dose
      of 120mg/kg for 16 days. Erythropenia, leucopenia was observed in ATR treated
      rats. Other hematological variables such as packed cell volume (PCV), hemoglobin
      concentration (HGB), mean cell hemoglobin concentration (MCHC), mean corpuscular
      volume (MCV), neutrophils (NEU), lymphocytes (LYM) and blood platelet (PLT)
      showed no significant change with respect to the control values. The activities
      of the antioxidant defense molecules including superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) and glutathione
      (GSH) were decreased; malondialdehyde (MDA) level increased but catalase (CAT)
      activity showed no change.Co-administration of Q5 did not prevent the oxidative
      stress and the hematological alterations caused by ATR. In these groups of
      animals, the values of PLT and NEUT were increased while LYM decreased indicating
      more pronounce hematological changes. The changes in both the biochemical and
      hematological variables were normalized to the control values on co
      administration of Q10. We suggest that the antioxidant activities of QT at a
      doses of 10mg/kg could be responsible for its protective effects against ATR
      induced oxidative stress and hematological toxicity.

PMID- 22416649
TI  - Affinity (tropism) of caprine arthritis encephalitis virus for brain cells.
AB  - One of the constraints in unraveling the mysteries blurring the advancement of
      research in the quest to totally put HIV problems under control is getting the
      appropriate animal model that would truly simulate human cases. This problem is
      more apparent in studies involving the central nervous system. Consequently, a
      viable animal model to generate information for the production of drugs and
      vaccines for the prevention and or control of lentiviral induced dementia in
      affected host animals is pertinent and vital. In this study, explant cultures
      prepared from the brain of new-born goat-kid were infected with CaprineArthritis
      Encephalitis (CAE) virus- a retrovirus affecting goats. The specific brain cell
      types infected by the (CAE) virus were determined using reverse-transcription
      polymerase chain reaction (RT-PCR) and transmission electron microscopy (TEM
      techniques). TEM showed that in 85 - 90% cases, microglia were the cells
      specifically infected by the virus. Amplification of the genomic sequence of the
      envelope and the gag genes by RT-PCR confirmed the presence of CAEV proviral DNA
      in the brain cells of affected animals. No productive infection of the astrocytes
      was observed. The results of this study showed a lot of similarities in the
      tropism of CAE virus infection of goat brain cells to that of HIV infection in
      humans thus suggesting the potential usefulness of the caprine model for the
      study of HIV neuropathology. The goat model system as a non-primate model
      therefore could be more adaptable as a simple animal model than primate models
      with their complexity of anthropological, environmental and safety problems.

PMID- 22416650
TI  - Inhibition of acute experimental colitis by a crude extract and diets containing
      seeds of Garcinia kola (heckel).
AB  - The protective effect of Garcinia kola (GK) crude extract on acetic acid induced
      colitis in rats was investigated. Colitis, a form of inflammatory bowel disease
      (IBD) is characterized by inflammation of colon. The pathology in colitis
      includes disruption of crypt architecture, inflammation of crypts, frank crypt
      abscesses, and hemorrhage or inflammatory cells in the lamina propria. Since
      oxidative stress plays an important role in the etiology of Inflammatory Bowel
      diseases,and Garcinia kola (GK), have been shown to reduce oxidative stress in
      the rat stomach.The present study was designed to investigate the effects of
      Garcinia kola on ulcerative colitis (UC) induced by acetic acid. Albino rats were
      divided into five groups; Group one served as control, group two received Normal
      saline, group three received 2.5% ethanol while groups four and five were given
      20mg/kg and 100mg/kg of crude extract of Garcinia kolarespectively. In another
      experiment, rats were fed for 2 weeks on normal rat diets but specially composed
      to contain 12.5%, 25% and 50% by weight of G kola. Colitis was induced by intra
      rectal administration of 6% acetic acid. The colonic damage was elucidated by
      macroscopic damage scores; colon wet weight, stool consistency and colonic edema
      (thickness of the colon). Intra-luminal administration of 6% acetic acid resulted
      in observable clinical and macroscopic signs of colitis.Pre-orally administered
      of crude extract of GK significantly reduced the colonic damage score (p<0.001),
      colon weight (p<0.001), thickness of the colon (p<0.001) and diarrhea
      (p<0.001).Histological examinations also indicated a marked reduction in tissue
      injury and inhibition in neutrophil infiltration in rats pretreated with crude
      extract of Garcinia kola. Results of this investigation provide experimental
      evidence of Garcinia kola as an anti-colitis agent.

PMID- 22416651
TI  - Pretreatment effect of magnesium on alloxan induced hyperglycemia in rats.
AB  - The role of vitamins and mineral supplementation in the management of Diabetes
      mellitus is not well elucidated. We therefore carried out a preliminary study to
      assess the effect of prior administration of Magnesium on induction of alloxan
      diabetes, a model of type 1 diabetes mellitus. Twenty Male albino rats were used
      for this study. The animals were divided into 4 groups of 5 animals each. Animals
      in group 1 were normal rats and were not given any treatment, these served as
      healthy control. Animals in group 2 were diabetic rats that were not given any
      treatment, they served as diabetic control. Animals in group 3 were treated with
      magnesium (100mg/kg) intraperitoneally one hour prior to alloxan (150mg/kg)
      administration. Animals in group 4 were given intraperitoneal injection of
      magnesium (100mg/kg) once, and blood samples were obtained one hour after
      administration. Blood samples were obtained from all animals after 48 hours and
      plasma glucose levels determined using the glucose oxidase method. There was
      significant increase (p<0.001) in plasma glucose level in the alloxan treated
      group when compared with the control. There was also a significant increase
      (p<0.01) in magnesium-pretreated diabetic group. However, there was a significant
      reduction (p<0.01) in blood glucose level 48 hours after alloxan administration
      in the magnesium pre-treated diabetic group when compared with the diabetic
      controls. Magnesium pretreatment may delay the onset of alloxan induced
      hyperglycemia and this may be due to the scavenging effect of magnesium on the
      highly reactive hydroxyl radicals (OH) which was generated through alloxan
      reaction.

PMID- 22416652
TI  - Effects of methanolic and chloroform extracts of leaves of Alstonei boonei on rat
      liver mitochondrial membrane permeability transition pore.
AB  - The effects of methanolic and chloroform extracts of the leaves of Alstonei
      boonei, a medicinal plant with anti-malarial, anti-inflammatory and analgesic
      properties, were assessed on liver mitochondrial membrane permeability transition
      (MMPT) pore were assessed in experimental animals in vitro and in vivo. The
      results obtained showed that calcium ions induced the opening of MMPT pore
      significantly (P< 0.05) in rat liver mitochondria, while spermine (0.1mM)
      inhibited calcium-induced opening of MMPT pore of these mitochondria thus,
      indicating that the mitochondria were intact, ab initio. The results further
      revealed the inhibitory effects of different concentrations of the various
      extracts of leaves of Alstonei boonei (200 microg/ml, 600 microg/ml, 1000
      microg/ml, 1400 microg/ml) compared with spermine. Specifically, the data
      revealed that methanolic and chloroform extracts of leaves of Alstonei boonei
      reversed calcium-induced opening of MMPT pore in a concentration-dependent manner
      (26.5%, 27.4%, 56.4%, 69.3%) for methanolic extract of Alstonei boonei and (9.6%,
      34.9%, 51.5% and 82.1%) for chloroform extract of Alstonei boonei, respectively.
      Although, the MMPT pore was not affected by low concentrations of the methanolic
      extract of Alstonei boonei (200 microg/ml and 600 microg/ml) in the absence of
      calcium, the extract at higher concentrations (1000 microg/ ml and 1400
      microg/ml) induced the opening of the pore in a concentration-dependent manner.
      Mitochondria isolated from Wistar strain albino rats orally exposed to various
      doses of the methanolic extract of Alstonei boonei exhibited pore opening in the
      absence of calcium. In this respect, maximum (112%) induction of pore opening was
      obtained at 250mg/kg body weight, while minimum (31%) induction of pore opening
      was obtained at 200mg/kg body weight. Calcium further increased the extent of
      opening of the MMPT pore in animals previously exposed to methanolic extract of
      Alstonei boonei. These findings suggest that certain bioactive components of
      Alstonei boonei may be involved in inhibiting the opening of the MMPT pore in
      vitro and in the induction of the opening of the pore at high doses of the
      extract with the eventual release of cytochrome C which is a prelude to the
      progression of programmed cell death.

PMID- 22416653
TI  - Effect of Telfairia occidentalis on erythrocyte indices of rats following acute
      blood loss.
AB  - Fluted pumpkin (Telfairia occidentalis) leaf is popularly used in soup and folk
      medicine preparation in the management of various diseases such as diabetics,
      anaemia, and gastrointestinal disorders in Nigeria. This study sought to
      investigate the effect of orally administered aqueous extract of T. occidentalis
      leaf on some erythrocyte indices in albino rats of the Wistar strain following
      acute blood loss. Thirty rats were divided into 6 equal groups. Blood loss
      (haemorrhagic anaemia) was induced by bleeding 30% of the blood volume of rats
      through the retro-orbital venus plexus in 3 groups (IV-VI). Group I served as the
      normal control. 10mg or 20mg/day of T. occidentalis leaf extract were
      administered orally, once daily to Groups II and III respectively, for 28 days.
      Group IV served as the bled control. Groups V and VI were bled animals to which
      10mg or 20mg/day of T. occidentalis leaf extract was administered orally, once
      daily respectively, for 28 days. On the 29th day, the rats (fasted overnight)
      were sacrificed by decapitation and blood was collected through the retro-orbital
      venus plexus and used for assessment of some erythrocyte indices: red blood cell
      count, haemoglobin concentration, haematocrit, white blood cell count, MCV, MCH,
      MCHC, and erythrocyte osmofragility. Telfairia occidentalis noticeable increased
      the red blood cell count of the treated bled rats with 10mg or 20mg/day of T.
      occidentalis leaf extract to give 11.90 x 10(12)/L and 11.91 x 10(12)/L
      respectively when compared to the bled control (10.85 x 10(12)/L), P<0.05). The
      20mg/day T. occidentalis treated group showed increase in MCV (43.98fl) when
      compared to the bled control (39.56fl). Erythrocyte osmofragility which was
      decreased in the bled control was further decreased noticeably by the 20mg T.
      occidentalis treated group. The improved erythrocyte indices, at 20mg/day of
      extract, and reduced erythrocyte osmofragility are indications oferythropoietic
      potential of T. occidentalis.

PMID- 22416654
TI  - Effect of defatted methanolic extract of Holarrhena floribunda leaves in sodium
      arsenite-induced clastogenecity in Wistar albino rats.
AB  - This study examined the effect of defatted methanolic extract of Holarrhena
      floribunda leaves on sodium arsenite-induced clastogenecity and toxicity in male
      wistar rats. Animals were randomly allotted into six groups of five rats each and
      treated as follows; Group A (sodium arsenite (NaAsO3)), Group B (100 mg/kg
      extract), Group C (100 mg/kg extract plus NaAsO3), Group D (200 mg/kg extract),
      Group E (200 mg/kg extract plus NaAsO3) and Group F had distilled water. Sodium
      arsenite (2.5 mg/kg) was given intraperitoneally once per week. The extract was
      administered through oral gavage for 28 consecutive days. Clastogenecity was
      evaluated by studying micronuclei formation in polychromatic erythrocytes cells
      (PCEs) in the bone marrow. Plasma levels of Gamma Glutamyl Transferase (aGT),
      Aspartate Amino Transferase (AST), Alanine Amino Transferase (ALT) were
      determined. Hepatic Reduced Glutathione (GSH), Superoxide Dismutase (SOD),
      Catalase (CAT), protein and lipid peroxidation were determined. Liver
      histopathological evaluation was also carried out.The results obtained show that
      NaAsO3-induced micronuclei formation in PCEs was reduced at 100 and 200 mg/kg of
      the extract by 7.7% and 38.5% respectively while elevated plasma aGT and ALT
      levels were significantly ameliorated (P<0.001). There was no significant
      difference in plasma AST levels and hepatic SOD activities in all the treated
      groups as compared with the control. Sodium arsenite-induced reduction of GSH
      concentration was elevated by the extract at 100 and 200 mg/kg by 18.5% and 11.9%
      respectively. The reduction of CAT activity by NaAsO3 was also ameliorated at 200
      mg/kg extract by 23.3%. The extract at 100 mg/kg significantly reduced NaAsO3
      induced lipid peroxidation by 16.4% (P < 0.05). Histological examinations showed
      that the extract at 100 mg/kg protected NaAsO3-induced liver damage. This study
      revealed that the leaf extract has potential to ameliorate clastogenecity and
      toxicity induced by sodium arsenite in rats.

PMID- 22416655
TI  - Induction of membrane permeability transition (MPT) pore opening by Buccholzia
      coriacea (Engl.) seeds in vitro in rat liver mitochondria.
AB  - Apoptosis involves a phenomenon termed mitochondrial permeability transition
      (MPT) which induces permeability of a voltage-dependent pore to solutes of
      smaller than 1500Da. Induction of MPT pore is beneficial in case of tumour cells
      while inhibition of the pore is relevant in conditions such as tissue wastage.
      The effects of methanol extracts of Buccholzia coriacea (MEBC) commonly known as
      'wonder kola' on MPT wa s assessed in vitro in normal rats inthe presence and
      absence of exogenous calcium- the triggering agent. MPT was estimated by the
      extent of mitochondrial swelling monitored spectrophotometrically as decreases in
      absorbance at 540nm. The results revealed that in the absence ofexogenous
      calcium, MPT pore opening was induced by MEBC at 200 microg/ml, 600 microg/ml,
      1000 microg/ml and 1400 microg/ml in a concentration-dependent manner by 21.0,
      7.6, 4.2, 3.5 folds, although higher concentrations of MEBC reduced pore opening.
      Pre-incubation of mitochondria with similar concentrations of MEBC for 5 minutes
      in the absence of calcium induced pore opening by 1.47, 10, 8.7 and 10.1 folds,
      respectively. Furthermore, mitochondrial membrane treated with MEBC (200
      microg/ml, 600 microg/ml, 1000 microg/ml and 1400 microg/ml) in the presence of
      exogenous calcium induced pore opening by 63.9%, 44.0%, 23.4% and 64.4%,
      respectively. Oral administration of MEBC at varying doses of 50 - 200mg/kg b.w
      to rats for 30 days had no significant effects (p>0.05) on MPT pore opening in
      the absence of calcium when compared to untreated animals. The liver function
      tests revealed that the activities of alanine and aspartate amino transferases,
      alkaline phosphatase, and a-glutammyl transferase were significantly (p>0.05)
      increased in serum of animals exposed to MEBC compared to control animals.
      Overall, Buccholzia coriacea induced MPT pore opening in vitro thus suggesting
      that certain bioactive components in the extract may prove useful in chemotherapy
      of tumor cells however, these bioactive agents seem to have been completely
      metabolized in vivo.

PMID- 22416656
TI  - Possible biochemical markers of antiretroviral therapy (ART) failure in resource
      constrained areas.
AB  - Possible biochemical parameters that can distinguish clinically-failing people
      living with HIV/AIDS (PLWHA) from clinically-stable PLWHA on antiretroviral
      therapy (ART) were investigated in a north central location of Nigeria. The major
      aim of the study was to determine possible diagnostic biochemical markers that
      can be helpful in resource- and manpower-poor environments. Eighty (80)
      consenting persons living with HIV/AIDS who were on combined ART while attending
      a tertiary hospital in the North Central part of Nigeria were recruited for the
      study. Fifty (50) persons had clinically failing (CF) conditions while 32 were
      clinically stable (CS). Of the 50 CF cases 32 persons switched drugs while 18 did
      not in the course of their ART. In all, serum total bilirubin, total protein,
      total cholesterol, albumin, alkaline phosphatase (ALP), glucose, creatinine, urea
      and CD4 cell count were assayed. The values of these parameters in the CF and CS
      persons were statistically compared. The same parameters in the CF cases that
      switched drugs and those that maintained their drugs were also statistically
      compared with the corresponding values for the same parameters in the clinically
      stable persons. Alkaline phosphatase activity and total cholesterol levels and
      CD4 count in the CF cases were significantly (pd"0.05) different from the values
      for the CS persons. Only creatinine levels in CF persons that switched drugs
      differed significantly (pd"0.05) from the corresponding values in CF, persons
      that did not switch drugs even when there was no difference in creatinine values
      between the latter and the CS persons. CD4 count and total cholesterol levels may
      serve as useful indicators of potential clinically-failing and/or clinically
      stable cases of PLWHA on antiretroviral therapy. Creatinine levels on the other
      hand, may be useful in distinguishing PLWHA that switched drugs and those that
      did not. These parameters may serve as reliable rapid assessment tools for
      HIV/AIDS research and diagnosis in resources-poor areas.

PMID- 22416657
TI  - The antimicrobial activities of processed Nigerian and South African black tea.
AB  - The antibacterial activity of processed Nigerian Lipton Tea and South African 5
      Roses Tea, extracted using distilled water, chloroform and 70% ethanol were
      determined against nine (9) enteropathogenic bacteria which includes; Bacillus
      subtilis, Proteus sp, Enterobacter sp., Klebsiella pneumoniae, Escherichia coli,
      Salmonella typhi, Salmonella paratyphi A, Salmonella arizona and Staphylococcus
      aureus. The 2 tea bags, Nigerian Lipton tea bag and the South African 5 Roses tea
      bag were extracted through Solvent extraction method using 3 extraction solvents;
      Distilled water, Chloroform and 70% Ethanol and then inoculated onto the Mueller
      Hinton agar plates containing the standard isolates at 6 different points on each
      plate. The zones of inhibition of the bacterial isolates produced by each of
      these tea - extracts were determined while meaningful antibacterial activities
      against five (5) of the standard isolates; Enterobacter sp., K. pneumoniae, S.
      paratyphi A, B. subtilis and S. aureus were observed. Lipton tea water-extract
      was a more effective antibacterial agent than water-extract of 5 Roses tea. While
      the 70% ethanol-extract of 5 Roses tea had the greatest antibacterial activity of
      all the different tea-extract used for the study, the chloroform-extracts of the
      tea bags had no antimicrobial effect on all the test organisms used.

PMID- 22416658
TI  - N-acetylcysteine pretreatment ameliorates mercuric chloride-induced oxidative
      renal damage in rats.
AB  - The effectiveness of the antioxidant thiol, N-acetylcysteine (NAC), in enhancing
      methylmercury (CH3HgCl) excretion and its utility as a possible antidote in
      CH3HgCl poisoning has been reported. NAC, however, has been reported to be
      ineffective in accelerating excretion of divalent toxic metals, including
      inorganic mercury, Hg2+. In this study, we evaluated the possible protective
      effect of short-term pretreatment with NAC against mercuric chloride (HgCl2)
      toxicity in rat model. This is aimed at determining its chemopreventive or
      prophylactic benefit in situations of high risk exposure
      (occupational/industrial) to mercury. Rats were divided into three treatment
      groups. Group I received saline (10 ml/kg) and served as control. Group II
      received HgCl2 (5mg/kg) and group III received NAC (10mg/kg) plus (5mg/kg). All
      administration was via intraperitoneal (i.p.) injection. Saline and NAC were
      administered for 5days and HgCl2 was administered to rats in groups II and III on
      the 5th day. Animals were sacrificed 24 hours after HgCl2 injection and samples
      obtained for biochemical evaluation. Results revealed that single i.p. injection
      of HgCl2 induced significant renal oxidative damage resulting in significant
      decrease in the activities of superoxide dismutase (SOD), catalase (CAT),
      glutathione-s-transferase (GST), depletion of reduced glutathione (GSH) and
      increase in malondialdehyde (MDA) levels in these rats. The activities of glucose
      6-phosphatase (G6Pase) and 5'-nucleotidase (5'-NTD) (markers of microsomal
      damage) also decreased in these HgCl2 treated rats. The oxidative damage induced
      by HgCl2 led to significant alterations in renal histology and caused functional
      impairment (indicated by elevated blood urea nitrogen (BUN) and serum creatinine)
      in these rats. NAC was effective in attenuating the oxidative damage, functional
      impairments and histopathological changes that characterized HgCl2 intoxication
      in this study. Renal antioxidant defense system was re-enforced by NAC, leading
      to increase in the activities of SOD, CAT, GST and decreases in GSH depletion and
      MDA level. Our results therefore reveal the ameliorative effect of NAC
      pretreatment against HgCl2 toxicity in vivo, thus, suggesting its usefulness as a
      possible chemoprophylactic agent during occupational or industrial exposure to
      inorganic mercury.

PMID- 22416659
TI  - Hibiscus sabdariffa ethanolic extract protects against dyslipidemia and oxidative
      stress induced by chronic cholesterol administration in rabbits.
AB  - Excessive intake of cholesterol (CHOL) and induction of free radical production
      play a critical role in the pathophysiology of several human diseases. Dietary
      therapy with plant products rich in flavonoids has been shown to provide benefits
      without the adverse effects of agents used in clinical practice. Hibiscus
      sabdariffa (HS) has been used for various purposes due to myriads of flavonoids
      present in it. In this study, the chemopreventive property of HS ethanolic
      extract (HSE) was investigated in dyslipidemia and oxidant stress associated with
      prolonged CHOL administration in rabbits. Twenty-five (25) adult male rabbits
      weighing between 1.5 and 1.7 kg were used and randomly divided into five groups
      of five rabbits per group. The CHOL-fed rabbits received 1 g/kg/day of CHOL
      suspended in 1 ml of corn oil for 8 weeks. Group 1 received 1 ml of corn oil and
      served as control. Group 2 was fed with CHOL only while groups 3, 4 and 5
      received daily doses ofcholestyramine (questran, 260 mg/kg), HSE 200 mg/kg and
      HSE 300 mg/kg respectively along with CHOL. Animals were sacrificed by cervical
      dislocation 24-hours after last dose. Enzymic and non-enzymic markers of
      oxidative stress and lipid profile were analysed in serum, liver, kidney and
      heart of rabbits. HSE significantly attenuated the alteration in lipid levels and
      antioxidant status induced by high CHOL intake in rabbits in this study. Both
      serum and tissue levels of low density lipoprotein-CHOL, triglycerides,
      phospholipids, and total CHOL decreased with increase in high density lipoprotein
      CHOL except in the heart, following treatment with HSE in CHOL-fed rabbits when
      compared with the untreated group (p<0.05). Similarly, HSE prevented CHOL-induced
      depletion of enzymic (superoxide dismutase, catalase) and non-enzymic (reduced
      glutathione, vitamin C) antioxidants with the attendant increases in lipid
      peroxidation and xanthine oxidase activity in these animals. The effectiveness of
      HSE in this condition was comparable with that of cholestyramine but with greater
      in potency. Data from this study demonstrate the hypolipidaemic and antioxidant
      activities of HSE and suggest its therapeutic potential in disorders of lipid
      metabolism and cardiovascular events associated with hypercholesterolemia.

PMID- 22416660
TI  - Antidiabetic properties of ethanolic extract of Cnidoscolus aconitifolius on
      alloxan induced diabetes mellitus in rats.
AB  - This research was designed to investigate the antidiabetic properties of
      ethanolic extract of Cnidoscolus aconitifolius in alloxan-induced diabetes
      mellitus in Wistar male albino rats. Thirty male albino rats were used. Diabetes
      mellitus was induced in five of the six groups (B-F) by a single intra-peritoneal
      injection at the dose of 100mg/kg after normal fasting blood glucose had been
      determined. Group A served as the positive control while groups C-E received
      100mg/kg, 500mg/kg and 1000mg/kg of Cnidoscolus aconitifolius extract
      respectively. Group B did not received any treatment while group F received
      chlorpropamide, a standard drug used in the treatment of diabetes mellitus. Blood
      glucose and body weights were monitored weekly for four weeks. Plasma lipids and
      electrolytes such as Total cholesterol, Triglyceride, Low Density Lipoproteins
      (LDL), High Density Lipoproteins (HDL), Creatinine and Blood Urea Nitrogen (BUN)
      were determined after four weeks of treatment with Cnidoscolus aconitifolius
      extract. The results show significant reduction (P<0.001) in the blood glucose in
      group C (100mg/kg of Cnidoscolus aconitifolius) when compared with diabetic
      control (Alloxan only) and other treatment groups. There was gradual increase in
      weight of all treatment groups compared with the diabetic control, which had
      progressive weight loss. Plasma cholesterol levels also significantly reduced
      (P<0.001) in rats treated with 1,000mg/kg Cnidoscolus aconitifolius extract. From
      this study, Cnidoscolus aconitifolius extract was found to considerably reduce
      blood glucose and plasma cholesterol levels and progressively increase weight
      gain in diabetic treated rats confirming its traditional use for the treatment of
      diabetes.

PMID- 22416661
TI  - Lymphatic filariasis in a rural community in Nigeria: a challenge ahead.
AB  - Lymphatic filariasis (LF) represents a major public health problem in tropical
      and subtropical regions of the world. Following the admission of a 65 year old
      man from Sowo village Abeokuta Ogun State with a case of LF at the Federal
      Medical Centre Abeokuta, a cross-sectional based survey was carried out to
      determine the occurrence and prevalence of LF in this village. Identification of
      the LF parasite was carried out with blood stained with Giemsa and examined under
      low power magnification for the presence of sheathed microfilaria. Out of 317
      persons examined 54 (17%) were microfilaraemic and their ages varied from 10 to
      70 years. The age group 40-49 has the highest prevalence of 36.5% and highest
      mean microfilaria count of 4.8mf/mL. In the age group 20-29, females (12.8%) were
      more infected than males (9.3%) and the difference was statistically significant
      (P=0.0042). In all more males (17.8%) were affected than females (16.9%)
      (P=0.9481) and the mean MF count in males (22.8mf/ML) was higher than females
      (21.7mf/ML). The prevalent rate of elephantiasis and hydrecoele observed in the
      community was 2.2% respectively. The result of this study confirms and observed a
      high prevalence rate of LF in this community. This finding establishes the need
      for Ministry of Health (MOH) and Global Alliance to Eliminate LF (GAELF) to carry
      out disease control activities through Annual Mass Drug Administration (MDA) in
      this community.

PMID- 22416662
TI  - Fate of Listeria monocytogenes and members of the Enterobacteriaceae group along
      the processing line of 'Wara' a Southwestern Nigeria soft cheese.
AB  - This study aimed at evaluating the survivability of Listeria monocytogenes and
      members of the Enterobacteriaceae group of organisms during the processing and
      storage of wara, a southwestern Nigerian un-ripened soft cheese. Pasteurized milk
      inoculated with L. monocytogenes at 10(1) or 10(2) CFU/ml was used to process the
      cheese. Samples were taken along the processing steps and throughout a five-day
      storage period at 15 and 28 degrees C for populations of L. monocytogenes and
      Enterobacteriaceae. On the fourth storage day, portions of the control cheese
      (not inoculated with L. monocytogenes) were fried in vegetable oil, mimicking the
      practice of southwestern Nigerian cheese processors. The results indicated that
      L. monocytogenes, at both inoculation levels, did not survive the processing of
      wara. In samples initially inoculated with 10(1) CFU/ml of L. monocytogenes, the
      Enterobacteriaceae counts increased from 3.35-3.48 Log10 CFU/g on the first day
      of storage to 7.63-8.46 Log10 CFU/g at 28 degrees C and 5.41-6.34 Log10 CFU/g at
      15 degrees C after storage for 5 days. The populations of the Enterobacteriaceae
      group increased with the extension of storage time in the contaminated, as well
      as the control cheeses. Overall, the survival of Enterobacteriaceae responded to
      storage temperatures. Frying significantly reduced the populations of
      Enterobacteriaceae. The study suggests that wara can serve as a vehicle to
      transmit illness if its microbial quality is not appropriately managed.

PMID- 22416663
TI  - Using geographical information system to model the spread of tuberculosis in the
      University of Ibadan, Nigeria.
AB  - Nigeria currently ranks as the fourth highest burdened nation with tuberculosis
      (TB) globally; hence, new perspectives of addressing treatment and control of the
      disease are needed. New technology, such as Geographical Information Systems
      (GIS), may be useful in this process. We therefore sought to identify
      geographical areas where on-going TB transmission was occurring by linking GIS
      technology with disease surveillance in a University community in Ibadan,
      Nigeria. Retrospective data of TB incidence between 2004 and 2007 from the Health
      Centre in the University were cartographically mapped to show current trends in
      the spread of the disease and its geographic dispersion among those infected
      using ArcGIS 9.2 software and Global Positioning System (GPS). A total of 71
      cases were detected over the study period. The mean age for the affected
      population was 27.76 +/- 8.46 (SD); fifty six (78.87%) patients being students
      while 15 (21.13%) were workers. The nearest neighbour distance analysis indicated
      a clustered pattern of locations; with zip code- 2 characterized by overcrowding
      and limited room space having increased likelihood of on-going transmission. This
      study therefore provides a preliminary synopsis of the uses of GIS in
      tuberculosis control in Nigeria; hence the need to explore it on a larger scale.

PMID- 22416664
TI  - Non-polio enteroviruses serotypes circulating in Nigeria.
AB  - Enteroviruses is one of the most common group of human pathogens, causing a wide
      range of acute symptoms involving the cardiac and skeletal muscles, central
      nervous system, pancreas,skin and mucous membranes. In spite of the success
      recorded in polio eradication globally, infections with other enteroviruses
      remain frequent and sometimes very serious, requiring hospitalization. In this
      study we determined the various circulating serotypes of non-polio enteroviruses
      (NPEVs) with a view to providing information on the activity of these viruses
      among the Nigerian children, who usually are the most affected. Stool samples
      were obtained from hospitalized children at two major secondary community
      hospitals in Ibadan and acute flaccid paralysis (AFP) cases from 26 states
      ofNigeria. A presumptive identification of NPEVs was based on growth in RD cells.
      Isolates were identified by neutralization assay using sera obtained from the
      Institute for Public Health and the Environment, the Netherlands. The problems
      associated with this assay prompted the use of genotypic method developed at the
      Centers for Disease Control, Atlanta, USA for the final identification of
      isolates. Neutralization assay identified the 138 isolates into echoviruses
      (43.5%), coxsackie B viruses (29.7%) and untypeable isolates (26.8%). Finally
      genotyping identified echoviruses (E3, E6, E7, E11, E12, E13, E14, E19, E20, E21,
      E24, E29, E30, E33), coxsackieviruses (CVA3, CVA4, CVA6, CVA17, CVB3, CVB5, CVB6)
      and enteroviruses (EV69, EV71). The causal association of isolates with different
      diseases was also established. Majority of the isolates belonged to the human
      enterovirus gropup B (HEV-B) specie, followed by 4 and 1 in the HEV-A and HEV-C
      species respectively. This study forms the basis of molecular epidemiology of
      NPEVs being established for the first time in Nigeria. The implication of the
      presence of neurotropic serotypes (E3, E6, E7, E11, E14, E20, E24, E29, E30,
      EV71, CVB3 and CVB5) is that AFP may still be prevalent following polio
      eradication.

PMID- 22416665
TI  - Effects of stresroak as an immunomodulator on birds vaccinated with newcastle
      disease vaccine.
AB  - The efficacy of Stresroak--an Ayurvedic product (India) was tested in cockerel
      chicks. Eighty day-old chicks were randomly allocated into four groups with 20
      birds per group. Group 1 received Stresroak at the recommended dosage of 1 ml/20
      birds for 5 days prior to the NDV vaccinations (i/o, LaSota and Komarov). Group 2
      received Stresroak at double the recommended dosage prior to vaccinations. Group
      3 received no treatment but had all the afore mentioned vaccinations while Group
      4 received neither treatments nor vaccinations and therefore served as the
      control group. Sera samples were analyzed by Haemagglutination Inhibition (HI)
      tests. There was no significant immunostimulation by Stresroak except on days 42
      and 63 of life during the period of this study. It is therefore concluded that
      the manufacturer's claim of immunomodulatory property of Stresroak could not be
      validated in the humoral immunity studied. It is therefore suggested that further
      works be conducted using immunosuppressed hosts like birds with subclinical IBD
      and coccidiosis. In addition, research can be extended to the cell-mediated
      immunity.

PMID- 22416666
TI  - Insight into the epidemiology of laboratory confirmed human tuberculosis in
      Ibadan, Nigeria.
AB  - Nigeria being one of the leading nations with the highest burden of tuberculosis
      (TB) urgently needs more impetus in the diagnosis of this disease judging from
      the increased incidence of human immunodeficiency virus/acquired immune
      deficiency syndrome (HIV/AIDS). As culture of mycobacteria provides the
      definitive diagnosis of TB, this study reviews its use in the confirmation of
      laboratory samples from patients presented at different clinics in Ibadan from
      April, 2004 to April, 2008. Fine needle aspirates, sputum and stool samples were
      collected from suspected tuberculous patients who were either seropositive or
      negative for HIV. The samples were processed and cultured using the Lowenstein
      Jensen media. Samples from 1, 992 patients were processed (males=892 and
      females=1100; age range=1 week old to 90 years); and from these, 19.9% (396/1992)
      were positive for TB. The result showed that culture was a useful tool for the
      confirmation of mycobateria in TB patients, those coinfected with TB/HIV as well
      as those suffering from tuberculous lymphadenitis. This work also shows its
      usefulness in the diagnosis of TB in children using stool samples. Despite the
      inherent limitations of culture, its optimisation will however be useful in
      handling complicated problems ofTB associated with HIV, multi drug resistance-TB
      (MDR-TB) and several cases of extrapulmonary TB which makes smear microscopy
      insensitive and non-specific. Finally, there is an urgent need to upgrade all the
      TB laboratories in the country to include culture and other modem diagnostic
      techniques that will facilitate prompt and efficient diagnosis of the disease and
      accelerate its control.

PMID- 22416667
TI  - Combining bifunctional chelator with (3 + 2)-cycloaddition approaches: synthesis
      of dual-function technetium complexes.
AB  - A new concept for the synthesis of dual-functionalized technetium (Tc) compounds
      is presented, on the basis of the reactivity of fac-{Tc(VII)O(3)}(+) complexes.
      The concept combines the "classical" bifunctional chelator (BFC) approach with
      the new ligand centered labeling strategy of fac-{TcO(3)}(+) complexes with
      alkenes ((3 + 2)-cycloaddition approach). To evidence this concept, fac
      {(99)TcO(3)}(+) model complexes containing functionalized 1,4,7-triazacyclononane
      (tacn) derivatives N-benzyl-2-(1,4,7-triazonan-1-yl)acetamide (tacn-ba) and
      2,2',2"-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (nota.3H) were synthesized
      and characterized. Whereas [(99)TcO(3)(tacn-ba)](+) [2](+) can be synthesized
      following a established oxidation procedure starting from the Tc(V) complex
      [(99)TcO(glyc)(tacn-ba)](+) [1](+), a new synthetic pathway for the synthesis of
      [(99)TcO(3)(nota)](2-) [5](2-) had to be developed, starting from
      [(99)Tc(nota.3H)(CO)(3)](+) [4](+) and using sodium perborate tetrahydrate
      (NaBO(3).4H(2)O) as oxidizing reagent. While [(99)TcO(3)(nota)](2-) [5](2-) is a
      very attractive candidate for the development of trisubstituted novel
      multifunctional radioprobes, (3 + 2)-cycloaddition reactions of [(99)TcO(3)(tacn
      ba)](+) [2](+) with 4-vinylbenzenesulfonate (styrene-SO(3)(-)) demonstrated the
      suitability of monosubstituted tacn derivatives for the new mixed "BFC-(3 + 2)
      cycloaddition" approach. Kinetic studies of this reaction lead to the conclusion
      that the alteration of the electronic structure of the nitrogen donors by, e.g.,
      alkylation can be used to tune the rate of the (3 + 2)-cycloaddition.

PMID- 22416668
TI  - Regional cerebral blood flow patterns in patients with freezing of gait due to
      lacunar infarction: SPECT study using three-dimensional stereotactic surface
      projections.
AB  - BACKGROUND: Although freezing of gait (FOG) is reportedly caused by
      cerebrovascular disease, few studies have examined its pathology. We examined
      regional cerebral blood flow (rCBF) patterns in patients with FOG resulting from
      chronic lacunar infarction using single-photon emission computed tomography
      (SPECT). METHODS: Among patients with chronic lacunar infarction treated at our
      outpatient unit, we performed N-isopropyl-p-[(123)I]-iodoamphetamine SPECT in
      seven patients with FOG (FOG group) and in 20 patients without FOG (non-FOG
      group). We analyzed and compared the SPECT data using three-dimensional
      stereotactic surface projections of the two groups. RESULTS: On z-score maps, the
      FOG group showed a significant reduction in rCBF in the bilateral anterior
      cingulate cortices compared with the non-FOG group. The mean z-score for the
      bilateral cingulate gyri was significantly higher in the FOG group than in the
      non-FOG group (p < .01). When the cingulate gyrus data of the anterior and
      posterior subregions were analyzed on a region-by-region basis, the mean z-score
      for the left anterior cingulate gyrus was significantly higher than that for the
      right cingulate gyrus (p < .05). CONCLUSION: These results suggest that anterior
      cingulate cortex dysfunction may be involved in the pathology of FOG in patients
      with chronic lacunar infarction.

PMID- 22416669
TI  - Characterization of changes in the proteome in different regions of 3D multicell
      tumor spheroids.
AB  - Three dimensional multicell tumor spheroids (MCTS) provide an experimental model
      where the influence of microenvironmental conditions on protein expression can be
      determined. Sequential trypsin digestion of HT29 colon carcinoma MCTS enabled
      segregation into four populations comprising proliferating cells from the surface
      (SL), an intermediate region (IR), nonproliferating hypoxic cells from the
      perinecrotic region (PN), and a necrotic core (NC). Total protein was extracted
      from each population and subjected to iTRAQ-based quantitative proteomics
      analysis. From a total of 887 proteins identified, 209 were observed to be up
      regulated and 114 were down-regulated in the PN and NC regions relative to the
      SL. Among the up-regulated proteins, components of glycolysis, TCA cycle, lipid
      metabolism, and steroid biosynthesis increased progressively toward the PN and NC
      regions. Western blotting, immunohistochemistry, and enzyme assays confirmed that
      significant changes in the expression of proteins involved in cellular metabolism
      occur in the nonproliferating fraction of cells within the viable rim. The
      presence of full length, functional proteins within the NC was unexpected, and
      further analysis demonstrated that this region contains cells that are undergoing
      autophagy. This study has identified possible targets that may be suitable for
      therapeutic intervention, and further studies to validate these are required.

PMID- 22416670
TI  - Formal nucleophilic substitution of bromocyclopropanes with azoles.
AB  - A highly diastereoselective protocol for the formal nucleophilic substitution of
      2-bromocyclopropylcarboxamides with azoles is described. A wide range of azoles,
      including pyrroles, indoles, benzimidazoles, pyrazoles, and benzotriazoles, can
      be efficiently employed as pronucleophiles in this transformation, providing
      expeditious access to N-cyclopropyl heterocycles.

PMID- 22416671
TI  - Antegrade endoscopic removal of retained urethral sling mesh in the bladder.
AB  - The midurethral sling has emerged as an effective, minimally invasive treatment
      for patients with stress urinary incontinence. Bladder penetration is a known
      complication that, if unrecognized, may result in retained intravesical mesh.
      This rare complication can cause patient discomfort as well as become a nidus for
      infection and bladder calculi. Because of the technique of sling passage, the
      site of retained sling material is often along the anterior bladder wall, making
      evaluation and treatment via traditional retrograde cystoscopy prohibitively
      difficult. We describe a novel and minimally invasive method to remove the sling
      material using antegrade access into the bladder in conjunction with holmium
      laser vaporization. In our series of six patients in whom retrograde cystoscopic
      treatment had failed, all were successfully treated with antegrade cystoscopy and
      reported improved urinary symptoms. This new technique provides a simple,
      minimally invasive, and effective method for removal of exposed sling mesh.

PMID- 22416672
TI  - Editorial Comment to Status of sex reassignment surgery for gender identity
      disorder in Japan.

PMID- 22416673
TI  - Dietitians use and recommend dietary supplements: report of a survey.
AB  - BACKGROUND: Dietary supplement use is common in the United States, with more than
      half of the population using such products. Nutrition authorities consistently
      advocate a "food first" approach to achieving nutritional adequacy but some,
      including the Academy of Nutrition and Dietetics (formerly the American Dietetic
      Association), also recognize that dietary supplements have a role to play in
      improving nutrient intake to support health and wellness. Surveys show that many
      health professionals use dietary supplements themselves and also recommend
      dietary supplements to their patients or clients. METHODS: As one component of a
      series of surveys of healthcare professionals (the "Life...supplemented" HCP
      Impact Studies), 300 registered dietitians were surveyed in 2009 regarding their
      personal use of dietary supplements and whether they recommend dietary
      supplements to their clients. Respondents were registered dietitians whose
      business involved seeing clients in a private practice or at a clinic. RESULTS:
      Seventy-four percent of the dietitians surveyed said they were regular users of
      dietary supplements, while 22% said they used dietary supplements occasionally or
      seasonally. The primary reasons for using dietary supplements were for bone
      health (58%), overall health and wellness (53%), and to fill nutrient gaps (42%).
      When asked if they "ever recommend dietary supplements to clients," 97% of the
      respondents said they did. The primary reasons were for bone health (70%), to
      fill nutrient gaps (67%), and overall health and wellness (49%). Eighty-seven
      percent of the dietitians agreed with the statement, "There are gaps in clients'
      diets that could effectively be addressed with dietary supplements." The
      dietitians surveyed said they followed healthy habits including eating a balanced
      diet (96%), managing stress (92%), visiting their own healthcare professional
      regularly (86%), exercising regularly (83%), maintaining a healthy weight (80%),
      and getting a good night's sleep (72%). Nearly all respondents (95%) expressed an
      interest in continuing education about dietary supplements on a variety of
      topics. CONCLUSIONS: Many dietitians, like other health professionals, use
      dietary supplements regularly as part of their own approach to a healthy diet and
      lifestyle. They also recommend dietary supplements to their clients or patients,
      to promote health.

PMID- 22416674
TI  - The clinical pain acceptance Q-sort: a tool for assessment and facilitation of
      pain acceptance.
AB  - The topic of pain acceptance can be clinically difficult to raise in a respectful
      way. This article introduces a method of managing the topic of pain acceptance in
      daily clinical practice: The clinical pain acceptance Q-sort. The Q-sort
      procedure comprises 13 small cards with printed statements concerning pain
      acceptance on the one side, score numbers on the other side. The procedure
      involves the patient handling and prioritizing the statements in a personally
      meaningful order. Both quantitative and qualitative use of the tool is possible.
      The method has a three-fold outcome: (1) topics of pain acceptance are presented
      in a multi-faceted way for the chronic pain patient, (2) an approximate
      assessment of the level of pain acceptance issues is offered to the clinician,
      and (3) good opportunities for a therapeutic discussion on pain acceptance are
      made available. The clinical pain acceptance Q-sort procedure may positively
      contribute to daily clinical work with pain acceptance in a straightforward way.
      The method provides options for assessment of pain acceptance, for better
      understanding of the patient, and for clinical training in psychological pain
      management.

PMID- 22416676
TI  - Impact of antiretroviral therapy interruption on plasma biomarkers of
      cardiovascular risk and lipids: 144-week final data from the STOPAR study.
AB  - OBJECTIVE: The aim of the study was to investigate changes in plasma biomarkers
      of cardiovascular risk and lipids in a CD4-guided antiretroviral therapy
      interruption study. METHODS: This was a substudy of a prospective, randomized,
      multicentre treatment interruption study. At months 12, 24 and 36, monocyte
      chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM
      1), interleukin-6 (IL-6), interleukin-8 (IL-8), soluble CD40 ligand (sCD40L),
      soluble P-selectin (sP-selectin), and tissue plasminogen activator (t-PA) were
      measured using a multiplex cytometric bead-based assay. Total cholesterol (total
      c), high-density lipoprotein cholesterol (HDL-c) and triglycerides (TG) were
      determined using standard methods. RESULTS: Fifty-four patients were included in
      the study [34 in the treatment continuation (TC) arm and 20 in the treatment
      interruption (TI) arm]. There were no differences at baseline between the groups,
      except in CD4 cell count, which was higher in the TI arm (P = 0.026), and MCP-1,
      which was higher in the TC arm (P = 0.039). MCP-1 and sVCAM-1 were increased
      relative to baseline at the three study time-points in the TI arm, with no
      changes in the TC arm. Soluble CD40L and sP-selectin were increased at month 36
      in both arms, with a greater increase in the TI arm (P = 0.02). t-PA was
      increased in both arms at the three time-points. Total-c, HDL-c and low-density
      lipoprotein cholesterol (LDL-c) were decreased in the TI arm at the three time
      points, with no changes in the total-c/HDL-c ratio. HIV viral load positively
      correlated with MCP-1 at months 12 and 24. Regression analysis showed a
      significant negative association of HDL-c with MCP-1 and sVCAM-1. CONCLUSIONS: A
      significant increase in cardiovascular risk biomarkers persisting over the
      prolonged study period was seen in the TI arm. This factor may contribute to the
      increased cardiovascular risk observed in previous studies.

PMID- 22416675
TI  - Characterization of LysB4, an endolysin from the Bacillus cereus-infecting
      bacteriophage B4.
AB  - BACKGROUND: Bacillus cereus is a foodborne pathogen that causes emetic or
      diarrheal types of food poisoning. The incidence of B. cereus food poisoning has
      been gradually increasing over the past few years, therefore, biocontrol agents
      effective against B. cereus need to be developed. Endolysins are phage-encoded
      bacterial peptidoglycan hydrolases and have received considerable attention as
      promising antibacterial agents. RESULTS: The endolysin from B. cereus phage B4,
      designated LysB4, was identified and characterized. In silico analysis revealed
      that this endolysin had the VanY domain at the N terminus as the catalytic
      domain, and the SH3_5 domain at the C terminus that appears to be the cell wall
      binding domain. Biochemical characterization of LysB4 enzymatic activity showed
      that it had optimal peptidoglycan hydrolase activity at pH 8.0-10.0 and 50
      degrees C. The lytic activity was dependent on divalent metal ions, especially
      Zn2+. The antimicrobial spectrum was relatively broad because LysB4 lysed Gram
      positive bacteria such as B. cereus, Bacillus subtilis and Listeria monocytogenes
      and some Gram-negative bacteria when treated with EDTA. LC-MS analysis of the
      cell wall cleavage products showed that LysB4 was an L-alanoyl-D-glutamate
      endopeptidase, making LysB4 the first characterized endopeptidase of this type to
      target B. cereus. CONCLUSIONS: LysB4 is believed to be the first reported L
      alanoyl-D-glutamate endopeptidase from B. cereus-infecting bacteriophages. The
      properties of LysB4 showed that this endolysin has strong lytic activity against
      a broad range of pathogenic bacteria, which makes LysB4 a good candidate as a
      biocontrol agent against B. cereus and other pathogenic bacteria.

PMID- 22416677
TI  - High-dose aprotinin, blood product transfusions, and short-term outcome in
      neonates and infants: a pediatric cardiac surgery center experience.
AB  - BACKGROUND: The efficacy of aprotinin, the most popular antifibrinolytic agent in
      congenital cardiac surgery, was still uncertain in small infants when its
      prophylactic use was suspended for safety reasons. The aim of this study is to
      describe associations between the prophylactic use of high-dose aprotinin, the
      need for blood product transfusions, and short-term outcome in neonates and
      infants with cardiac surgery. METHODS/MATERIALS: This retrospective study
      included all patients younger than 1 year undergoing surgery with cardiopulmonary
      bypass through 42 months, before and after withdrawal of aprotinin. Each patient
      who received aprotinin was matched with a control with similar baseline and
      surgical characteristics, who have not received any antifibrinolytic agent.
      Associations between the use of aprotinin and the exposure to red blood cells,
      fresh frozen plasma, and platelet transfusions were estimated from a logistic
      regression model, and the exposure to additional transfusions from a polytomous
      regression model. RESULTS: Matching resulted in two groups of 283 patients each,
      well balanced except for the priming volume and the ultrafiltration rate, larger
      in the aprotinin group. After adjustment for the priming volume and
      ultrafiltration rate, there was no significant association between the use of
      aprotinin, the exposure to any blood product transfusion, or the exposure to
      additional transfusions, the rate of re-exploration for bleeding, and short-term
      outcome. Two patients in the control group required re-exploration for bleeding.
      CONCLUSIONS: No association was found between the prophylactic use of aprotinin,
      blood product transfusions, and short-term outcome in this population of neonates
      and infants.

PMID- 22416678
TI  - Plexiform melanocytic schwannoma: a mimic of melanoma.
AB  - We present a unique dermal tumor for which we propose the term plexiform
      melanocytic schwanomma. The proliferation consisted of lobules of epithelioid and
      spindled cells with S100, Melan-A and HMB-45 positivity but without obvious
      melanin pigmentation. The nuclei were moderately pleomorphic in some areas, and
      in a few areas the mitotic index was elevated. Schwannian differentiation was
      inferred from the presence of areas with nuclear palisading resembling Verocay
      bodies, from plexiform architecture and from the presence of a thin rim of EMA
      positivity around the tumor. Array-based comparative genomic hybridization showed
      genomic losses that overlap with those seen in sporadic schwanomma. The
      differential diagnosis included melanoma, melanotic schwannoma and cutaneous
      melanocytoneuroma, and we compare and contrast our case with these entities.

PMID- 22416679
TI  - Diabetes distress, but not depressive symptoms, is associated with glycaemic
      control among Japanese patients with type 2 diabetes: Diabetes Distress and Care
      Registry at Tenri (DDCRT 1).
AB  - AIMS: To investigate the association between glycaemic control, diabetes distress
      and depressive symptoms among Japanese patients with Type 2 diabetes. METHODS:
      Cross-sectional data from 3305 patients with Type 2 diabetes were obtained from a
      baseline assessment of a diabetes registry at a general hospital in Japan. The
      Centre for Epidemiologic Studies Depression scale and Problem Areas in Diabetes
      scale were used to measure depressive symptoms and diabetes-related distress,
      respectively. Modified Poisson regression analysis was used to estimate the
      relative risks for poor glycaemic control across the quartiles of Centre for
      Epidemiologic Studies Depression scale and Problem Areas in Diabetes scale
      scores. RESULTS: The average age of the participants was 64.9 years and the
      average HbA(1c) level was 58.1 mmol/mol (7.5%). Clinically significant levels of
      depressive symptoms (Centre for Epidemiologic Studies Depression scale scores >=
      16) were reported by 27.8% of participants. These scores significantly correlated
      with Problem Areas in Diabetes scale scores (r = 0.4354, P < 0.0001). Diabetes
      distress, but not depressive symptoms, was significantly associated with higher
      HbA(1c) levels. The relative risks for poor glycaemic control (HbA(1c) >= 64
      mmol/mol; 8.0%), when adjusted for age, sex, BMI, type of diabetes therapy and
      duration of diabetes, was 67% higher among patients with Problem Areas in
      Diabetes scale scores in the highest quartile (>= 26.25) compared with those in
      the lowest quartile (0-3.75). CONCLUSION: A significant association between
      glycaemic control and diabetes-related distress, but not depressive symptoms, was
      observed in Japanese patients with Type 2 diabetes.

PMID- 22416680
TI  - Comparative GC/MS analysis of essential oils extracted by 3 methods from the bud
      of Citrus aurantium L. var. amara Engl.
AB  - A comparative study of steam distillation extraction (SDE), reflux extraction
      (RE), and ultrasound-assisted extraction (USE) was conducted for the extraction
      of essential oils from the bud of Citrus aurantium L. var. amara Engl. Each
      method was evaluated in terms of qualitative and quantitative composition of the
      isolated essential oil by gas chromatography/mass spectrometry (GC/MS). The
      extract yields of essential oil were 0.16%, 2.18%, and 2.34%, respectively. A
      total of 82 compounds were identified by GC/MS. The main components obtained by
      SDE were terpinen-4-ol (20.98%), dipentene (11.67%), terpinene (9.24%), those by
      RE were palmitic acid (20.61%), 2-chloroethyl linoleate (14.54%), tetracosane
      (12.26%), and alpha-linolenic acid (11.24%), and those by USE were tetracosane
      (11.32%), heneicosane (11.06%), and palmitic acid (8.76%). Comparative analysis
      indicated that SDE was favorable for the extraction of monoterpene hydrocarbons,
      sesquiterpene hydrocarbons, alcohols, and carbonyl compounds, RE and USE had
      certain advantages in the extraction of aliphatic saturated hydrocarbons, organic
      acids, and esters. It is concluded that different extraction methods may lead to
      different yields of essential oils; the choice of appropriate method is very
      important to obtain more desired components with higher physiological activities.
      PRACTICAL APPLICATION: C. aurantium oils from different plant parts have great
      economic, medicinal, and nutritional values because of their wide-spectrum
      biological activities. The essential oil from C. aurantium L. var amara is one of
      the best C. aurantium oils. The data presented in this article will help us
      understand the relationship between essential oils and its extraction methods and
      know more about the aromatic components of Citrus aurantium bud. The methods
      established in this study will provide useful reference information for further
      studies, and offer essential oil industries with helpful guidance in practice.

PMID- 22416681
TI  - Structural characterization of the exopolysaccharide produced by Streptococcus
      thermophilus 05-34 and its in situ application in yogurt.
AB  - An exopolysaccharide (EPS) producing strain was isolated from Tibetan kefir
      grains in China, which was identified by 16S rDNA tests and designated as
      Streptococcus thermophilus 05-34. The high-performance liquid chromatography
      analysis showed that it was composed of galactose and glucose in a molar ratio of
      1.0:0.8 with a molecular mass of 2.5 * 10(4)  Da. EPS was further revealed to
      have alpha-d-glucose, alpha-d-galactose, beta-d-glucose, and beta-d-galactose by
      Fourier transform infrared spectroscopy combined with 1D (1) H nuclear magnetic
      resonance spectroscopy. The length of EPS ranged from 10 to 100 nm and the
      maximal height of lumps was 2.5 nm through atomic force micrograph analysis.
      Furthermore, yogurt fermented with EPS-producing S. thermophilus 05-34 exhibited
      lower susceptibility to whey separation, higher viscosity, and sensory scores
      than those made with non-EPS-producing strain in yogurt production. These results
      suggested that EPS-producing Streptococcus thermophilus 05-34 provided a
      potential application in the fermented dairy industry.

PMID- 22416682
TI  - Changes of polyphenols, sugars, and organic acid in 5 Vitis genotypes during
      berry ripening.
AB  - The concentrations of sugars, organic acids, and polyphenols during berry
      ripening in 5 grape genotypes were analyzed using HPLC and HPLC-MS to determine
      which were correlated. Veraison is critical stage during grape berry development,
      and marks the beginning of ripening. Glucose and fructose accumulated sharply in
      a 1: 1ratio, though the concentration of fructose was slightly higher than that
      of glucose at maturation. Malic acid and tartaric acid were the dominant organic
      acids, and they decreased rapidly during berry ripening. The 5 cultivars
      contained 28 anthocyanins and 8 other polyphenols. All anthocyanins accumulated
      and were positively correlated with the sugars and negatively correlated with the
      organic acids. Hydroxycinnamic acids declined and were positively correlated with
      anthocyanin contents. Changes in flavanols and flavonols different among the 5
      genotypes, with flavonols positively correlated with anthocyanin content, but the
      flavanols procyanidin B1and epicatechin negatively correlated with anthocyanins
      content. There were obvious differences in patterns of change of polyphenols
      among 5 grape genotypes. PRACTICAL APPLICATION: The results could be used for
      improving grape berry quality during ripening and developing a comprehensive
      database of primary and secondary metabolites in the Vitis for grape breeding.

PMID- 22416683
TI  - Antioxidant activity of medicinal plant extracts in cookies.
AB  - The antioxidant activity of ethanolic extracts of parsley, buckthorn, mint,
      caraway, and their mixture "Vitalplant" was evaluated, and the potential of
      "Vitalplant" mixture extract to retard the process of lipid oxidation in cookies
      was tested. The antioxidant activity was estimated by 2 direct (ESR) and 4
      indirect (spectrophotometric) tests and correlated with the total phenolic and
      flavonoid content. The potential of "Vitalplant" mixture extract to retard the
      process of lipid oxidation in cookies was measured by thiobarbituric acid (TBA)
      reactive-substances assay (TBARS) and DPPH (1,1-diphenyl-2-picryl-hydrazyl) test.
      Significantly different (P < 0.05) amounts of total phenolics were found among
      extracts in the following order: mint > buckthorn > "Vitalplant" > parsley >
      caraway. Total flavonoid content varied from 0.510% (parsley) to 2.05%
      ("Vitalplant"). A statistically significant correlation was found between IC(50)
      values on DPPH and total flavonoid content of the samples (r=- 0.94, P < 0.05)
      and between IC(50) values on DPPH and IC(50) values on O(2) (.-) scavenging
      activity (r= 0.89, P < 0.05). A correlation between reducing activity and total
      phenolic content was found to be positive and statistically significant (r= 0.94,
      P < 0.05). "Vitalplant" mixture exhibited a relatively high antioxidant activity
      in most of the tests, which can be explained by synergistic effects of the
      ingredients of which it is composed. Finally, "Vitalplant" extract addition (2%,
      4%, and 6%) improved antioxidant activity and oxidative stability of the cookies
      in dose-dependent manner. PRACTICAL APPLICATION: Supplementation of cookies with
      a mixture of Petroselini fructus, Frangulae cortex, Mentha piperitae folium,
      Carvi fructus can retard the process of lipid oxidation and elevate antioxidant
      activity of the final product.

PMID- 22416684
TI  - Evaluation of the free radical scavenging activity of Cynomorium songaricum Rupr.
      by a novel DPPH-HPLC method.
AB  - A novel DPPH-HPLC method was successfully developed for evaluating the free
      radical scavenging activity of Cynomorium songaricum Rupr. The analysis was
      achieved on a YMC C(30)  column with the gradient elution by using water and
      methanol as mobile phase. The intraday and interday precisions were less than
      4.36%. The correlation coefficients of the calibration curve for the standard
      antioxidants exceeded 0.9967. The proposed method was found to be simple, rapid,
      and sensitive for evaluating the free radical scavenging activity of natural
      product. Quantitative analyses of the samples showed that the free radical
      scavenging activity of the samples from different grown sites varied
      significantly.

PMID- 22416685
TI  - Characterization of a 12 kDa thermal-stable antigenic protein in bovine blood.
AB  - We have previously developed an immunoassay based on monoclonal antibody (MAb)
      Bb1H9 for quantitative detection of ruminant blood in processed food and
      feedstuffs. The purpose of this study was to characterize the unknown 12 kDa
      thermal-stable ruminant-specific antigenic protein recognized by MAb Bb1H9 in
      order to better define the application scope of the developed assay. Extracts
      obtained from raw and heat-treated bovine blood-derived products were analyzed
      with indirect ELISA and Western blot. Target proteins resolved by 2D
      electrophoresis were subjected to N-terminal sequencing. Results indicated that
      the 12 kDa protein is a monomer of the tetrameric hemoglobin molecule (64.5 kDa)
      and that the heme group is not required for its binding with MAb Bb1H9. This MAb
      can be utilized as a probe for red blood cell derived products of ruminant origin
      in raw or processed food and feedstuffs to enforce labeling regulations and to
      address consumer concerns. PRACTICAL APPLICATION: MAb Bb1H9 represents the first
      antibody with the capacity to recognize bovine hemoglobin both in the absence and
      presence of the heme group, regardless of the heat treatment. MAb Bb1H9 can
      therefore be utilized in immunoassays by manufacturers and regulators to detect
      any ingredients containing hemoglobin or globin (hemoglobin without the heme
      group) in both raw and processed food and feed materials for product quality
      control and labeling law enforcement.

PMID- 22416686
TI  - Antioxidant capacity of different fractions of vegetables and correlation with
      the contents of ascorbic acid, phenolics, and flavonoids.
AB  - The antioxidant capacity of different fractions of 17 vegetables were analyzed
      using ferric reducing antioxidant power assay (FRAP assay) after water and
      acetone extractions. The contents of ascorbic acid, phenolics, and flavonoids
      were determined and their correlations with FRAP value were investigated. The
      results showed that the peel or leaf fractions of vegetables were stronger than
      the pulp or stem fractions in antioxidant capacity based on total FRAP value.
      Lotus root peel was the highest and cucumber pulp the lowest in total FRAP value
      among the vegetable fractions analyzed. All water extracts were higher in FRAP
      value than the acetone extracts. The FRAP value was significantly correlated with
      the contents of ascorbic acid, phenolics, or flavonoids in water extracts, in
      which the phenolics contributed most based on multivariate regression analysis.
      We conclude that different vegetable fractions were remarkably different in
      antioxidant capacity. The phenolics are responsible mostly for the antioxidant
      capacity of vegetables in vitro.

PMID- 22416687
TI  - Central composite design for the optimization of supercritical carbon dioxide
      fluid extraction of fatty acids from Borago officinalis L. flower.
AB  - In the present study, fatty acids and essential oils of the flower of borage
      (Borago officinalis L.) were obtained by supercritical carbon dioxide fluid
      extraction under different conditions. The extracts obtained were compared to
      oils of borage flower oil isolated by hydrodistillation. The obtained oils were
      analyzed by gas chromatography mass spectrometry. The compounds were identified
      according to their retention indices and mass spectra. The experimental
      parameters of supercritical fluid extraction (SFE) were optimized using a central
      composite design after a full factorial experimental design. Extraction yields
      based on SFE varied in the range of 0.02% to 1.96% (w/w), and the oil yield based
      on the hydrodistillation was 0.05% (v/w). The optimum conditions of SFE were
      obtained at a pressure of 350 atm, a temperature of 65  degrees C, a methanol
      modifier volume of 100 MUL, and static and dynamic extraction time of 10 min.
      Main components of the extracts under optimum SFE conditions were palmitic acid,
      linoleic acid, gamma-linolenic acid, and oleic acid. The results indicated that
      by using the suitable extraction conditions, SFE is more effective than the
      conventional hydrodistillation method in the extraction of fatty acids and the
      preservation of its quality. PRACTICAL APPLICATION: SFE is a good technique for
      the extraction of oils from plants. The extraction yields by SFE are more than
      the conventional method. SFE is used on a large scale for production of essential
      oils and pharmaceutical products from plants.

PMID- 22416688
TI  - Response surface methodology for meat-like odorants from the Maillard reaction
      with glutathione II: the tendencies analysis of meat-like donors.
AB  - Understanding the flavor effect of molecules on food products is fundamental for
      the food technologist. In this study, the formation of different meat-like
      compounds was controlled by various influence factors. Furthermore, the concept
      of interrelationships between Maillard reaction products (MRPs) was demonstrated
      by statistical analysis for the first time, which provides data and hence
      production system parameters by which to generate and optimize meat-like flavors
      through Maillard reactions. We report here the analysis and synthesis trend of
      the 13 meat-like donors which are regarded as forming the major flavor compounds
      of cooked meat. Response surface methodology (RSM) has not previously been
      reported in the literature as a technique to identify which parameters have the
      greatest influence on the synthesis of these flavor compounds. RSM has been used
      here to identify the influence of initial pH and DeltapH on flavor compound
      generation. As all DeltapH had positive RSM values between 0.5 and 1.5 it can be
      concluded that MRPs of this meat flavor-adapted system would be mostly acidic.
      These positive values also indicate that under this condition the Maillard
      reaction is stable and will therefore promote more meat-like flavor compounds to
      be generated. In addition to DeltapH, varied concentrations of glutathione,
      cysteine, thiamine, and xylose were investigated for their ability to influence
      the generation of meat-like flavors.

PMID- 22416689
TI  - Effect of sourdough on quality and acceptability of wheat flour tortillas.
AB  - As an alternative on the search for functional food products, this study
      evaluated the use of sourdough in the preparation of wheat flour tortillas. The
      sourdough was elaborated with Lactobacillus sanfranciscensis and the wheat flour
      tortillas were prepared with different concentrations of mother sponge (5%, 15%,
      and 25%) and fermentation times (1 and 3 h) at room temperature (25 +/- 2 
      degrees C). Quality (diameter, height, color, pH, stretchability scores, and
      Kramer shear cell results) of wheat tortillas was evaluated after 24 h of
      preparation. The mother sponge concentration and fermentation time affected some
      quality parameters and acceptability properties (taste, aroma, color, opacity,
      and rollability). In addition, the sourdough tortillas had higher stretchability
      values than control tortillas. Since most of the prepared sourdough tortillas had
      acceptability values similar to those of tortilla controls, the introduction of
      sourdough is a viable means to incorporate additional nutritional and
      nutraceutical value into wheat tortillas.

PMID- 22416690
TI  - Turmeric powder and starch: selected physical, physicochemical, and
      microstructural properties.
AB  - Turmeric powder and its starch were characterized for physical, physicochemical,
      and microstructural characteristics. X-ray diffractogram indicated that turmeric
      starch to be of B type. Dried and cured-dried turmeric powder samples showed
      higher water-holding capacity (3.62 and 4.78 g/g, respectively) compared to
      isolated starch (1.07 g/g) at 30  degrees C. Non-Newtonian shear-thinning
      characteristics were observed with turmeric powder dispersion containing 10%
      (w/w) solids. A power law model fitted well to correlate the shear-rate and shear
      stress data (r= 0.993 to 0.999, P<= 0.01) for both samples. Apparent viscosities
      of isolated turmeric starch and cured-dried turmeric powder dispersion containing
      10% (w/w) solids were 1.29 +/- 0.03 and 7.57 +/- 0.39 mPa s, respectively.
      Microstructure of starch particles showed a smooth flat outer surface. The
      approximate length and breadth of isolated elliptical starches were 25 and 10 MUm
      while the thickness was about 5 MUm. PRACTICAL APPLICATION: Isolation and
      characterization of starch from an unconventional source like turmeric rhizome
      indicate a potential application as a functional ingredient in foods and
      pharmaceutical industries including agglomerated products.

PMID- 22416691
TI  - In vitro antioxidant activity of different cultivars of banana flower (Musa
      paradicicus L.) extracts available in India.
AB  - Six different cultivars of banana flowers (Musa paradicicus) (Kathali, Bichi,
      Shingapuri, Kacha, Champa, and Kalabou) were analyzed for the content of
      polyphenol expressed as gallic acid equivalent and flavonoid expressed as
      quercetein equivalent, and the in vitro total antioxidative activities of the
      flower extracts were compared with standard and expressed as trolox equivalent.
      The reducing power, 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS*(+)) scavenging
      activities, inhibition of lipid peroxidation in a linoleic acid emulsion system,
      and liposome peroxidation system were measured and compared with respective
      standard antioxidants. Iron-mediated Fenton reaction was carried out to evaluate
      the protective effect of the extract of banana flower (Kacha cultivar) against
      H(2)O(2)-induced DNA damage. The Kacha variety contains the maximum amount of
      polyphenol (11.94 +/- 0.03 mg of gallic acid equivalent/g of dry weight) and
      flavonoid (0.174 +/- 0.001 g of quercetin equivalent/g of polyphenol). It also
      has the highest total antioxidant capacity, DPPH radical scavenging activity, and
      ABTS*(+) radical scavenging activity with a least EC(50) value of 0.051 mg/mL.
      Hepatic cell damage in iron-mediated Fenton reaction caused by free radicals is
      reduced by the banana flower extract. On the basis of the results obtained, the
      banana flowers are found to be a potential source of natural antioxidants. This
      is the first report on the antioxidant properties of the extracts from banana
      flowers. The study suggests that the flowers of M. paradicicus that are found in
      India and consumed as vegetable can provide valuable functional ingredients that
      help in the prevention of oxidative stress.

PMID- 22416692
TI  - Flour mill stream blending affects sugar snap cookie and Japanese sponge cake
      quality and oxidative cross-linking potential of soft white wheat.
AB  - The purpose of this research was to study the functional differences between
      straight grade (75% extraction rate) and patent (60% extraction rate) flour
      blends from 28 genetically pure soft white and club wheat grain lots, as
      evidenced by variation in sugar snap cookie and Japanese sponge cake quality.
      Functional differences were examined relative to arabinoxylan content, protein
      content, and oxidative cross-linking potential of flour slurries. Oxidative cross
      linking measurements were obtained on flour slurries with a low shear Bostwick
      consistometer and considered endogenous oxidative cross-linking potential (water
      alone) or enhanced oxidative cross-linking potential (with added hydrogen
      peroxide-peroxidase). A 2-way ANOVA indicated that flour blend was the greater
      source of variation compared to grain lot for all response variables except water
      extractable arabinoxylan content. Patent flours produced larger sugar snap
      cookies and Japanese sponge cakes, and contained significantly less total and
      water-unextractable arabinoxylans, protein, and ash than did straight grade
      flours. Patent flours produced more viscous slurries for endogenous and enhanced
      cross-linking measurements compared to the straight grade flours. The functional
      differences between patent and straight grade flours appear to be related to the
      particular mill streams that were utilized in the formulation of the 2 flour
      blends and compositional differences among those streams.

PMID- 22416693
TI  - Effect of co-inoculation of Saccharomyces cerevisiae and Lactobacillus fermentum
      on the quality of the distilled sugar cane beverage cachaca.
AB  - The effect of Lactobacillus fermentum in co-inoculation with Saccharomyces
      cerevisiae UFLA CA11 on the quality of cachaca (sugar cane spirit) was evaluated.
      The co-inoculation was first evaluated in flask fermentation, and subsequently,
      yeast and bacteria were co-cultured at approximately 10(5) CFU/mL and 10(8)
      CFU/mL, respectively, in 4 consecutive batches. L. fermentum did not affect the
      growth or activity (sugar consumption and fermentation rate) of S. cerevisiae
      UFLA CA11 during fermentation. The physicochemical analysis revealed a higher
      concentration (Tukey test) of aldehydes (22.07 mg/100 mL anhydrous alcohol) in
      cachaca produced by co-inoculation. Analysis of volatile compounds using GC-FID
      demonstrated that cachaca produced by co-inoculation had higher concentrations of
      acetaldehyde (25.15 mg/L), ethyl acetate (30.17 mg/L), and 2,3-butanedione
      (170.39 MU/L), while cachaca produced by UFLA CA11 contained higher
      concentrations of ethyl lactate (1205.98 MU/L), propionic acid (127.97 MU/L),
      butyric acid (2335.57 MU/L), and 1-pentanol (469.23 MU/L). The lowest
      concentration of acetic acid measured by HPLC was found in cachaca obtained with
      UFLA CA11. The sensory analysis, performed using the Mann-Whitney test, revealed
      that cachaca produced by co-inoculation differed from that produced by UFLA CA11
      in taste and aroma. PRACTICAL APPLICATION: This study reports on the use of a
      mixed culture of Saccharomyces cerevisae and Lactobacillus fermentum to produce
      cachaca and shows the influence of co-inoculation of yeast and bacteria on the
      quality of this beverage.

PMID- 22416694
TI  - Change of volatile compounds in fresh fish meat during ice storage.
AB  - The change of volatile compounds in fresh fish meat during 3- to 4-d ice storage
      was investigated for several fishes using an electronic nose system and a gas
      chromatography-mass spectrometer (GC/MS) with headspace solid-phase micro
      extraction (SPME). Principal component analyses for samples using the electronic
      nose system revealed that the increase of some volatile compounds during storage
      was rapid in sardine (Sardinops melanostictus), jack mackerel (Trachurus
      japonicus), and chub mackerel (Scomber japonicus); moderate in yellowtail
      (Seriola quinqueradiata), skipjack (Katsuwonus pelamis), and young oriental
      bluefin tuna (Thunnus thynnus). In contrast to these fishes, the change was
      little in "white meat" fishes such as red seabream (Chrysophrys major), Japanese
      seabass (Lateolabrax japonicus), flatfish (Paralichthys olivaceus), puffer
      (Lagocephalus wheeleri), and bartail flathead (Platycephalus indicus). SPME-GC/MS
      analysis showed that some aldehydes and alcohols such as 1-heptanol, (E)-2
      octenal, (E)-2-hexenal, 1-pentanol, (E,E)-2,4-heptadienal,2,4-hexadienal, 1
      hexanol, 4-heptenal, and so forth increased rapidly in jack mackerel and chub
      mackerel, slowly in skipjack, and a little in red seabream and puffer during the
      storage. The increase of these compounds was considered to have an effect on the
      change of electronic nose response. Hexanal was a dominant compound increased
      from the beginning of the storage in jack mackerel. The increase of volatile
      compounds was little in red seabream and puffer. The increase of these aldehydes
      and alcohols was thought to be an appropriate marker for monitoring the freshness
      of "fresh" fish except for white meat fish. PRACTICAL APPLICATION: The results of
      this study are ready to apply for preventing fishy off-flavor of fisheries
      products. Lipid oxidative derivatives other than trimethylamine contributed to
      fresh fish flavor; therefore, to prevent lipid oxidation seemed important.

PMID- 22416695
TI  - Determination of volatile compounds in apple pomace by stir bar sorptive
      extraction and gas chromatography-mass spectrometry (SBSE-GC-MS).
AB  - A method based on stir bar sorptive extraction combined with gas chromatography
      mass spectrometry detection (SBSE-GC-MS) has been optimized with the aim of
      applying it to the analysis of apple pomace. The method allowed the
      identification of 124 volatile compounds after 3 h of extraction with a precision
      (RSDs) ranging between 2% (linalool) and 11% (ethyl hexanoate). Its use in
      analyzing varietal apple pomace revealed the interest of this substrate as
      regards its content in aromas. From a semi-quantitative point of view, the higher
      content in aldehydes and esters of the Blanquina variety is worth highlighting,
      as are the greater concentration of acids in the Clara variety and the higher
      content of terpenes and norisoprenoides in the Coloradona variety. In contrast,
      the Ernestina and Perico varieties presented the lowest levels of aromas.
      PRACTICAL APPLICATION: The analysis of varietal apple pomaces showed the
      importance of this type of waste in the food industry, both for its content in
      aromas such as for its use as substrate in biotechnological processes.

PMID- 22416696
TI  - A colored avocado seed extract as a potential natural colorant.
AB  - There is an increasing consumer demand for and scientific interest in new natural
      colorants. Avocado (Persea americana) seed when crushed with water develops an
      orange color (= 480 nm) in a time-dependent manner. Heat treatment of the seed
      prevented color development, whereas the addition of exogenous polyphenol oxidase
      (PPO), but not peroxidase restored color development. Color development was also
      inhibited by the addition of tropolone, an inhibitor of PPO. Color formation
      resulted in a decrease in the concentration of polyphenols indicating utilization
      for color formation. The orange color intensified as the pH was adjusted from 2.0
      to 11.0, and these changes were only partially reversible when pH was adjusted
      from 7.5 to 11.0 in the presence of oxygen, but completely reversible when the pH
      was changed in the absence of oxygen. The color was found to be stable in
      solution at -18  degrees C for 2 mo. These results suggest that the avocado seed
      may be a potential source of natural colorant, and that color development is PPO
      dependent. PRACTICAL APPLICATION: There is growing public and scientific interest
      in the development of natural alternatives to synthetic colorants in foods.
      Extracts of turmeric, paprika, and beets are examples of food-derived natural
      colorants. Avocado seeds, which represent an under-utilized waste stream, form a
      stable orange color when crushed in the presence of air. Our data indicate that
      avocado seed represents a potential source of new natural colorants for use in
      foods.

PMID- 22416697
TI  - Antioxidant and antimicrobial properties of polyphenolic fractions from selected
      Moroccan red wines.
AB  - The present study is the first effort to a comprehensive evaluation of the
      antioxidant and antimicrobial activities of fractionated red wines from Morocco.
      The results obtained revealed that the wine samples were characterized by a
      higher phytochemical concentration than the same variety of wines with a
      different geographical origin and other more consumed red wines, confirming what
      was reported in a previous authors' work. The most phenolic-rich fractions were
      the ones containing phenolic acids and quercetin glucoronides from Syrah and
      Merlot wine samples while Cabernet Sauvignon exhibited the highest monomeric
      anthocyanin content. The antioxidant activity of wine extracts was tested by
      ferric reducing antioxidant power and 1,1-diphenyl-2-picrilhydrazyl assays.
      Samples revealed a higher reducing capacity than radical scavenging property and
      a good correlation between antioxidant activity and polyphenolic content values.
      As regards the antimicrobial properties, each fraction exhibited activity against
      a broad spectrum of food-borne microorganisms, revealing not only a moderate to
      high natural preserving capacity, but also potentially beneficial influence on
      human health. PRACTICAL APPLICATION: In consideration of the scarcity of data
      regarding composition and biological properties of Moroccan red wines, the
      present study may represent a valuable reference for wine consumers and
      producers.

PMID- 22416698
TI  - Soybean (Glycine max) oil bodies and their associated phytochemicals.
AB  - Soybean oil bodies were isolated from 3 cultivars (Ustie, K98, and Elena) and the
      occurrence of 2 classes of phytochemicals (tocopherol isoforms and isoflavones)
      and strength of their association with isolated oil bodies was evaluated.
      Tocopherol is shown to be closely associated with soybean oil bodies; delta
      tocopherol demonstrated a significantly greater association with oil bodies over
      other tocopherol isoforms. Isoflavones do not show a significant physical
      association with oil bodies, although there is some indication of a passive
      association of the more hydrophobic aglycones during oil body isolation.
      PRACTICAL APPLICATION: Oil bodies are small droplets of oil that are stored as
      energy reserves in the seeds of oil seeds, and have the potential to be used as
      future food ingredients. If oil body suspensions are commercialized on a large
      scale, knowledge of the association of phytochemicals with oil bodies will be
      valuable in deciding species of preference and predicting shelf life and
      nutritional value.

PMID- 22416699
TI  - Assessment of some Australian red wines for price, phenolic content, antioxidant
      activity, and vintage in relation to functional food prospects.
AB  - Twenty-three Cabernet Sauvignon wines from the Mudgee region and thirty-two
      Shiraz wines from the Hunter Valley region were analyzed for phenolic content and
      antioxidant activity. Concentrations of (+)-catechin, quercetin, and
      transresveratrol, total phenolic content, and DPPH antioxidant activity varied
      considerably, both within and between varieties. Individual phenols, total
      phenols, and antioxidant activity were correlated with price and vintage. Shiraz
      wines showed positive and significant correlations for catechin and quercetin
      concentrations with total phenols, antioxidant activity, and vintage; and for
      total phenols and antioxidant activity with vintage. Cabernet Sauvignon wines
      showed positive and significant correlations for quercetin concentration with
      total phenols and antioxidant activity. There was a negative and significant
      correlation found between price and antioxidant activity for Cabernet Sauvignon
      wines. Results are discussed in terms of the potential for wine to be considered
      a functional food. PRACTICAL APPLICATION: We report on potential health benefits
      (antioxidant activity) of 55 wines typical of 2 geographically close, but
      distinct, wine regions of Australia. Our results highlight the variability in
      functional components as an issue that needs further research and consideration
      in relation to wine as a functional food. The price of studied wines is not
      reflective of their health functionality, based on antioxidant activities.

PMID- 22416700
TI  - Evaluation of selected quality parameters to monitor essential oil alteration
      during storage.
AB  - Several analytical methods including high-performance liquid chromatography
      (HPLC) were applied on essential oils to establish a set of suitable quality
      parameters for monitoring changes during storage. For this purpose, 7 essential
      oils derived from various plant families were exposed to possible worst-case
      conditions for up to 3 mo at 38  degrees C under cool white light in the presence
      of atmospheric oxygen. After storage and immediate freezing at -80  degrees C to
      stop further alterations until analysis, individual physicochemical parameters
      were assessed and are discussed with regard to the precision of the respective
      method as well as suitability to monitor aging processes. To determine
      conductivity and pH values, a work-up of essential oils by water extraction was
      established. Conductivity, peroxide value as well as pH turned out to be suitable
      parameters to picture alterations. Additionally, HPLC fingerprints were monitored
      by diode array detection to track underlying chemical changes in essential oil
      composition. PRACTICAL APPLICATION: This study evaluates a set of analytical
      parameters to track changes during essential oil storage. On this basis, quality
      alterations can be monitored.

PMID- 22416701
TI  - Whey protein film with oxygen scavenging function by incorporation of ascorbic
      acid.
AB  - Residual O(2) in a package headspace can be removed by an O(2)-absorbing sachet,
      which can be harmful if swallowed by the consumer, or by a chemically-active
      plastic packaging film, which is difficult to recycle. An edible, O(2)-absorbing
      film would avoid these disadvantages. The objective of our research was to assess
      the O(2)-scavenging potential of an edible whey protein isolate (WPI) film
      incorporating ascorbic acid (AA). AA at 0.05, 0.1, or 0.2 M was added to 5% (w/w)
      heat-denatured WPI film-forming solutions with WPI : glycerol (Gly) ratio of 1:
      1.00, 1: 0.80, or 1: 0.67. The pH of solutions was then adjusted to 3.5 (below
      pK(a1) of AA), to stabilize AA against oxidation, before film casting. The
      mechanical properties, O(2) permeabilities, and thermal transitions of films were
      measured. Activation of the O(2)-scavenging function of the AA-incorporated films
      was accomplished by adjustment of the films to pH >= 7. O(2)-scavenging ability
      of AA-incorporated WPI films was determined by measuring residual O(2) in the
      headspace of a high-barrier container. Incorporation of AA into WPI film
      decreased film tensile strength and further reduced O(2) permeability at each WPI
      : Gly ratio. AA-containing films adjusted to pH >= 7 demonstrated O(2) absorption
      proportional to AA content, consistent with theoretical O(2)-scavenging capacity.
      Thermal transition measurements indicated that AA was involved in WPI structural
      modification and decreased the degradation temperature of WPI-based film. The
      demonstrated O(2)-scavenging function, improved O(2) barrier and acceptable
      mechanical properties of AA-incorporated films indicate potential commercial
      usefulness. PRACTICAL APPLICATION: Ascorbic acid-incorporated whey protein film
      with oxygen scavenging function can be used to extend shelf lives of a wide
      variety of oxygen-sensitive products by eliminating headspace oxygen as well as
      oxygen permeating through the packaging wall over time. Edible oxygen-scavenger
      film has the advantages of avoiding both accidental consumption and
      nonrecyclability of conventional oxygen scavenger systems.

PMID- 22416702
TI  - Rheology of milk foams produced by steam injection.
AB  - Rheology of milk foams generated by steam injection was studied during the
      transient destabilization process using steady flow and dynamic oscillatory
      techniques: yield stress (tau(y) ) values were obtained from a stress ramp (0.2
      to 25 Pa) and from strain amplitude sweep (0.001 to 3 at 1 Hz of frequency);
      elastic (G') and viscous (G") moduli were measured by frequency sweep (0.1 to 10
      Hz at 0.05 of strain); and the apparent viscosity (eta(a) ) was obtained from the
      flow curves generated from the stress ramp. The effect of plate roughness and the
      sweep time on tau(y) was also assessed. Yield stress was found to increase with
      plate roughness whereas it decreased with the sweep time. The values of yield
      stress and moduli-G' and G"-increased during foam destabilization as a
      consequence of the changes in foam properties, especially the gas volume
      fraction, phi, and bubble size, R(32) (Sauter mean bubble radius). Thus, a
      relationship between tau(y) , phi, R(32) , and sigma(surface tension) was
      established. The changes in the apparent viscosity, eta, showed that the foams
      behaved like a shear thinning fluid beyond the yield point, fitting the modified
      Cross model with the relaxation time parameter (lambda) also depending on the gas
      volume fraction. Overall, it was concluded that the viscoelastic behavior of the
      foam below the yield point and liquid-like behavior thereafter both vary during
      destabilization due to changes in the foam characteristics. PRACTICAL
      APPLICATION: Studying the transient rheology of milk foams during destabilization
      contributes to our knowledge of the relationships between the changes in foam
      properties: texture and mouth feel during the consumption of hot foamed
      beverages.

PMID- 22416703
TI  - A microwave and ohmic combination heater for uniform heating of liquid-particle
      food mixtures.
AB  - Microwave and ohmic combination heating was proposed to improve the uniformity of
      thermal processing of particulate foods. Thermal patterns of a liquid-particle
      mixture in a small test cell were studied using both experimental and simulation
      approaches. Carrot cubes (10 mm * 10 mm * 10 mm) and 0.1% NaCl salt solution were
      used as model foods. The temperature distribution of solid and liquid phases was
      examined using individual and combination heating methods. Under ohmic heating,
      the liquid was heated faster by 18.9  degrees C after 250 s. The heating rate of
      a carrot cube was faster than liquid under microwave heating and temperature rise
      of carrot was approximately 11.2  degrees C higher than that of solution after
      heating of 70 s. Samples experienced different heating patterns over time during
      the combination heating. Carrot samples showed a thermal lead initially when
      heated under microwave and the trend reversed during the second stage when ohmic
      heating was applied. Liquid-particle temperature difference was reduced as the
      combination heating proceeded, and came to be less than 2  degrees C at the end.
      Results obtained from simulation showed similar patterns and all prediction data
      agreed well with the experimental data. The prediction errors for sample
      temperatures ranged from 5.7% to 11.6%. The results provided better understanding
      for designing a continuous flow combination heater that can produce uniform
      temperature of solid-liquid mixtures. PRACTICAL APPLICATION: If successful, this
      combination heating technique will find its way to effective aseptic or sterile
      processing of low acid multiphase foods containing large particulates (such as
      soups with meatballs or vegetables) that has not been a commercial reality in the
      United States.

PMID- 22416704
TI  - Polyethylene glycol grafted polyethylene: a versatile platform for nonmigratory
      active packaging applications.
AB  - Nonmigratory active packaging, in which bioactive components are tethered to the
      package, offers the potential to reduce the need for additives in food products
      while maintaining safety and quality. A challenge in developing nonmigratory
      active packaging materials is the loss of biomolecular activity that can occur
      when biomolecules are immobilized. In this work, we describe a method in which a
      biocompatible polymer (polyethylene glycol, PEG) is grafted from the surface of
      ozone-treated low-density polyethylene (LDPE) resulting in a surface
      functionalized polyethylene to which a range of amine-terminated bioactive
      molecules can be immobilized. Free radical graft polymerization is used to graft
      PEG onto the LDPE surface, followed by immobilization of ethylenediamine onto the
      PEG tether. Ethylenediamine was used to demonstrate that amine-terminated
      molecules could be covalently attached to the PEG-grafted film. Changes in
      surface chemistry and topography were measured by attenuated total reflectance
      Fourier transform infrared spectroscopy, contact angle, atomic force microscopy,
      scanning electron microscopy, and X-ray photoelectron spectroscopy. We
      demonstrate the ability to graft PEG onto the surface of polymer packaging films
      by free radical graft polymerization, and to covalently link an amine-terminated
      molecule to the PEG tether, demonstrating that amine-terminated bioactive
      compounds (such as peptides, enzymes, and some antimicrobials) can be immobilized
      onto PEG-grafted LDPE in the development of nonmigratory active packaging.
      PRACTICAL APPLICATION:   Nonmigratory active packaging offers the potential for
      improving food safety and quality while minimizing the migration of the active
      agent into food. In this paper, we describe a technique to modify polyethylene
      packaging films such that active agents can be covalently immobilized by a
      biocompatible tether. Such a technique can be adapted to a number of applications
      such as antimicrobial, antioxidant, or immobilized enzyme active packaging.

PMID- 22416705
TI  - Two unsaturated fatty acids with potent alpha-glucosidase inhibitory activity
      purified from the body wall of sea cucumber (Stichopus japonicus).
AB  - One therapeutic approach for preventing diabetes mellitus and obesity is to
      retard the absorption of glucose via inhibition of alpha-glucosidase. Two
      unsaturated fatty acids with strong alpha-glucosidase inhibitory activity, 7(Z)
      octadecenoic acid (1) and 7(Z),10(Z)-octadecadienoic acid (2), were purified from
      the body wall of Stichopus japonicus. IC(50) values of compounds 1 and 2 were
      0.51 and 0.67 MUg/mL against Saccharomyces cerevisiae alpha-glucosidase and 0.49
      and 0.60 MUg/mL against Bacillus stearothermophilus alpha-glucosidase,
      respectively. These compounds mildly inhibited rat-intestinal sucrase and
      maltase. In addition, both compounds showed a mixed type of inhibition against S.
      cerevisiae alpha-glucosidase and were very stable under thermal and acidic
      conditions up to 60 min. The K(I) and K(IS) values of compounds 1 and 2 were 0.44
      and 0.22 MUg/mL, and 0.39 and 0.13 MUg/mL, respectively. PRACTICAL APPLICATION:
      One therapeutic approach for preventing diabetes mellitus is to retard the
      absorption of glucose via inhibition of alpha-glucosidase. In this study, 2 fatty
      acids with strong alpha-glucosidase-inhibitory activity, 7(Z)-octadecenoic acid
      and 7(Z),10(Z)-octadecadienoic acid, were purified and identified from sea
      cucumber. Therefore, sea cucumber fatty acids can potentially be developed as a
      novel natural nutraceutical for the management of type-2 diabetes.

PMID- 22416706
TI  - High pressure homogenization increases the in vitro bioaccessibility of alpha-
      and beta-carotene in carrot emulsions but not of lycopene in tomato emulsions.
AB  - The correlation between food microstructure and in vitro bioaccessibility of
      carotenes was evaluated for tomato and carrot emulsions (5% olive oil) subjected
      to high pressure homogenization (HPH) at varying degrees of intensity. The aim
      was to investigate whether additional mechanical disruption of the food matrix
      could be utilized to further increase the carotene bioaccessibility of an already
      pre-processed material. The carotene bioaccessibility of the samples was measured
      after simulated in vitro digestion, carotene release to the oil phase was
      estimated by Confocal Raman spectroscopy and, to measure active uptake of
      carotenes, Caco-2 cells were incubated with the digesta of selected samples. HPH
      did not notably affect the retention of carotenes or ascorbic acid but
      significantly increased both the release and micellar incorporation of alpha- and
      beta-carotene in carrot emulsions 1.5- to 1.6-fold. On the other hand, in vitro
      bioaccessibility of lycopene from tomato was not increased by HPH under any of
      the conditions investigated. Instead, the results suggested that lycopene
      bioaccessibility was limited by a combination of the low solubility of lycopene
      in dietary lipids and entrapment in the cellular network. Carotene uptake by Caco
      2 cells appeared to be mainly dependent upon the carotene concentration of the
      digesta, but cis-trans isomerization had a significant impact on the
      micellarization efficiency of carotenes. We therefore conclude that HPH is an
      interesting option for increasing the bioaccessibility of carotenes from fruits
      and vegetables while maintaining a high nutrient content, but that the results
      will depend on both food source and type of carotene. PRACTICAL APPLICATION: A
      better understanding of the correlation between the processing of fruits and
      vegetables, microstructure and nutrient bioaccessibility can be directly applied
      in the production of food products with an increased nutritional value.

PMID- 22416707
TI  - Essential oil of Curcuma longa inhibits Streptococcus mutans biofilm formation.
AB  - Curcuma longa (C. longa) has been used as a spice in foods and as an
      antimicrobial in Oriental medicine. In this study, we evaluated the inhibitory
      effects of an essential oil isolated from C. longa on the cariogenic properties
      of Streptococcus mutans (S. mutans), which is an important bacterium in dental
      plaque and dental caries formation. First, the inhibitory effects of C. longa
      essential oil on the growth and acid production of S. mutans were tested. Next,
      the effect of C. longa essential oil on adhesion to saliva-coated hydroxyapatite
      beads (S-HAs) was investigated. C. longa essential oil inhibited the growth and
      acid production of S. mutans at concentrations from 0.5 to 4 mg/mL. The essential
      oil also exhibited significant inhibition of S. mutans adherence to S-HAs at
      concentrations higher than 0.5 mg/mL. S. mutans biofilm formation was determined
      by scanning electron microscopy (SEM) and safranin staining. The essential oil of
      C. longa inhibited the formation of S. mutans biofilms at concentrations higher
      than 0.5 mg/mL. The components of C. longa essential oil were then analyzed by GC
      and GC-MS, and the major components were alpha-turmerone (35.59%), germacrone
      (19.02%), alpha-zingiberene (8.74%), alphar-turmerone (6.31%), trans-beta
      elemenone (5.65%), curlone (5.45%), and beta-sesquiphellandrene (4.73%). These
      results suggest that C. longa may inhibit the cariogenic properties of S. mutans.

PMID- 22416709
TI  - Optimization of culture condition for ACEI and GABA production by lactic acid
      bacteria.
AB  - Gamma-aminobutyric acid (GABA) and angiotensin-converting enzyme inhibitor (ACEI)
      are compounds which can influence hypertension. The goal of this study is to
      optimize the culture condition for GABA and ACEI production by Lactobacillus
      plantarum NTU 102 fermented skim milk. In this study, we used 3-factor-3-level
      Box-Behnken design combining with response surface methodology, where the 3
      factors represent the concentration of skim milk, the concentration of monosodium
      glutamate, and culture temperature. Best conditions for GABA and ACEI production
      differed. The results indicated that L. plantarum NTU 102 produced the highest
      combined levels of GABA and ACEI at 37  degrees C, in milk having 8% to 12%
      nonfat solids supplemented with 0.6% to 1% MSG. Agitation of the medium during
      fermentation had no effect on GABA or ACEI production but extended incubation (up
      to 6 d) increases levels of the bioactive compounds. L. plantarum NTU 102
      fermented products may be a potential functional food source for regulating
      hypertension.

PMID- 22416711
TI  - Inhibition of Listeria monocytogenes by exposure to a combination of nisin and
      cold-pressed terpeneless Valencia oil.
AB  - Listeria monocytogenes is an important foodborne pathogen and its control in
      foods is a significant challenge. This study evaluated the effectiveness of nisin
      and cold-pressed terpeneless Valencia oil (CPTVO) on limiting L. monocytogenes
      growth. Disk diffusion assays were performed to determine the effects of CPTVO
      and nisin individually and in combination. Together, these antimicrobials
      produced a zone of inhibition that was significantly larger (P < 0.05) than zones
      correlating to CPTVO or nisin individually. Furthermore, L.
      monocytogenesDeltasigB had an increased sensitivity to the combination treatment.
      Growth experiments performed in brain heart infusion (BHI) broth revealed the
      effects of nisin and CPTVO, individually and in combination on L. monocytogenes
      growth rate. When L. monocytogenes was grown in BHI containing 0.025% CPTVO and
      26 IU/mL nisin, no growth inhibition was observed relative to the control.
      However, exposure to CPTVO at 0 h followed by the introduction of nisin at 15 h
      resulted in a statistically significant (P < 0.05) reduction in growth. This
      approach to inhibiting L. monocytogenes has potential as an all-natural,
      generally-recognized-as-safe multiple hurdle intervention that may be applicable
      for ready-to-eat products in which L. monocytogenes is likely to cause foodborne
      illness.

PMID- 22416710
TI  - Survival, acid and bile tolerance, and surface hydrophobicity of
      microencapsulated B. animalis ssp. lactis Bb12 during storage at room
      temperature.
AB  - Survival, acid and bile tolerance, and surface hydrophobicity of
      microencapsulated Bifidobacterium animalis ssp. lactis Bb12 were studied during
      storage at room temperature (25  degrees C) at low water activity (0.07, 0.1, and
      0.2). Two types of alginate-based systems were prepared with and without mannitol
      as microencapsulant of B. animalis ssp. lactis Bb12. Formation of gel beads
      containing cells was achieved by dropping each emulsion into CaCl(2)  solution;
      then, the beads were freeze dried. Survival, acid tolerance during 2-h exposure
      in de Man, Rogosa, Sharpe (MRS) broth at pH 2.0, bile tolerance during 8-h
      exposure in MRS broth containing taurocholic acid at pH 5.8, and retention of
      surface hydrophobicity were determined after freeze drying and during storage.
      The result showed that neither alginate nor alginate-mannitol formulation was
      effective in protecting B. animalis ssp. lactis Bb12 during freezing and freeze
      drying. The viability in alginate-mannitol and alginate formulations after freeze
      drying was 6.61 and 6.34 log CFU/g, respectively. Storage at low a(w)  improved
      survival, acid tolerance, bile tolerance, and surface hydrophobicity retention of
      microencapsulated B. animalis ssp. lactis Bb12 when compared with controlled
      storage in an aluminum foil (with a(w)  of 0.38 and 0.40 for alginate-mannitol
      and alginate formulations, respectively). Alginate mannitol was more effective
      than the alginate system during a short period of storage, but its effectiveness
      decreased during a long period of storage (80% survival at 10 wk). Nevertheless,
      storage of microencapsulated B. animalis ssp. lactis Bb12 in an aluminum foil
      without a(w)  adjustment during 10 wk at room temperature was not effective
      (survival was 64% to 65%).

PMID- 22416712
TI  - In situ inhibition of Escherichia coli isolated from fresh pork sausage by
      organic acids.
AB  - The main aim of this study was to evaluate the inhibitory effect of different
      concentrations of organics acids citric, lactic, acetic, and propionic on E. coli
      isolated from pork sausage. Two experiments were performed in vitro,
      respectively: agar disc diffusion and minimum inhibitory concentration (MIC)
      determination. In agar disc diffusion, the minimum concentration of 1.29 M of
      citric acid inhibits bacterial growth. There was no statistically significant
      difference in the MIC of citric and lactic acids; citric and lactic acids were
      more effective than acetic and propionic acids. Based on in vitro results, lactic
      and citric acids were added to pork sausages with E. coli. The addition of citric
      acid caused a significant reduction (P < 0.01) in the pH of the sausages. Citric
      acid was most effective 15 d after inoculation; E. coli counts were reduced by
      4.53 log units compared with time 0. Due to late inhibitory action of citric acid
      in the study, its effect may be more effective over E. coli in sausage that
      requiring longer storage, such as fermented sausages.

PMID- 22416713
TI  - Rapid detection of Listeria monocytogenes in raw milk with loop-mediated
      isothermal amplification and chemosensor.
AB  - Loop-mediated isothermal amplification (LAMP) allows a rapid amplification of
      nucleic acids under isothermal conditions. It can be combined with a rhodamine
      based dual chemosensor for much more efficient, field-friendly detection of
      Listeria monocytogenes. In this report, LAMP was performed at 63  degrees C for
      10 min, followed by a rapid reaction of DNA amplification and the byproduct,
      pyrophosphate ion, with a rhodamine-based dual chemosensor and Cu(2+) is
      visualized as a disappearance of red color. The detection limit of L.
      monocytogenes by the LAMP-chemosensor was 8 to 10 cells per reaction tube, and
      the total assay time including 10 min for rapid DNA extraction was approximately
      30 min. Data on naturally contaminated raw milk samples indicated that the LAMP
      method was highly specific and sensitive, giving 100% concordance with the ISO
      10560 reference method. The results showed that the LAMP-chemosensor method has
      the advantages of better sensitivity and speed and less dependence on equipment
      than the standard Polymerase Chain Reaction for specifically detecting low levels
      of L. monocytogenes DNA, and this can be useful in the field as a routine
      diagnostic tool. PRACTICAL APPLICATION: The LAMP-chemosensor method reported here
      provided a powerful tool for detection of L. monocytogenes in raw milk samples
      due to its specificity, sensitivity, and rapidity.

PMID- 22416714
TI  - Survival of Salmonella serovars introduced as a post-aging contaminant during
      storage of low-salt Cheddar cheese at 4, 10, and 21  degrees C.
AB  - The microbiological stability of low-salt cheese has not been well documented.
      This study examined the survival of Salmonella in low-salt compared to regular
      salt Cheddar cheese with 2 pH levels. Cheddar cheeses were formulated at 0.7% and
      1.8% NaCl (wt/wt) with both low and high-pH and aged for 12 wk resulting in four
      treatments: 0.7% NaCl and pH 5.1 (low-salt and low-pH); 0.7% NaCl and pH 5.5 (low
      salt and high-pH); 1.8% NaCl and pH 5.7 (standard-salt and high-pH); and 1.8%
      NaCl and pH 5.3 (standard-salt and low-pH). Each treatment was comminuted and
      inoculated with a 5-serovar cocktail of Salmonella at a target level of 4 log
      CFU/g, then divided and incubated at 4, 10 and 21  degrees C for up to 90, 90,
      and 30 d, respectively. Salmonella counts decreased by 2.8 to 3.9 log CFU/g in
      all treatments. In the initial period of survival study, standard-salt treatments
      exhibited significantly lower Salmonella counts compared to low-salt treatments.
      The pH levels did not exhibit obvious significant effect in the Salmonella
      survival in low-salt treatments. Salmonella counts declined gradually regardless
      of a continuous increase in pH (end pH of 5.3 to 5.9) of low-salt treatments at
      all study temperatures. Salmonella counts were reduced faster at 21  degrees C
      storage. Although there were significant reductions in Salmonella counts, the
      treatments demonstrated survival of Salmonella for up to 90 d when stored at 4 or
      10  degrees C and for up to 30 d at 21  degrees C, the need for good sanitation
      practices to prevent postmanufacturing cross contamination remains. PRACTICAL
      APPLICATION: Low-salt aged Cheddar cheese could not support the growth of
      inoculated Salmonella and in fact gradual reduction in Salmonella count occurred
      during storage. Besides being nutritionally better, low or reduced salt Cheddar
      are safe as their full salt counterparts and that salt may only be a minor food
      safety hurdle regarding the post-aging contamination and growth of Salmonella.
      However, the treatments could not demonstrate complete destruction of Salmonella
      for up to 90 d when stored at 4 or 10  degrees C and for up to 30 d at 21 
      degrees C, the need for good sanitation practices to prevent postmanufacturing
      cross-contamination remains.

PMID- 22416715
TI  - All 4 bile salt hydrolase proteins are responsible for the hydrolysis activity in
      Lactobacillus plantarum ST-III.
AB  - In vertebrates, bile salt hydrolysis plays an essential role in fat metabolism.
      Bile salts are synthesized in the liver. And in the small intestine glycine and
      taurine are de-conjugated from bile salts by the enzyme bile salt hydrolase (BSH)
      from intestinal microbes. However, the mechanism of bile salt hydrolysis in
      Lactobacillus plantarum is still ambiguous. Four predicted bile salt hydrolase
      (bsh) genes from L. plantarum ST-III were cloned into Escherichia coli. The
      function of these genes was explored by overexpression. All 4 proteins that were
      studied showed activity against glycine- or taurine-conjugated bile salts.
      Substrate preference was also observed in BSH proteins, especially for the enzyme
      BSH1, which had high hydrolysis activity for glycodeoxycholic acid. These results
      suggest that all 4 bile salt hydrolases may be responsible for the bile salt
      hydrolysis activity in L. plantarum ST-III. PRACTICAL APPLICATION:
      Hypercholesterolemia is considered one of the major risk factors for coronary
      heart disease. More interest has focused on intestinal microbes because of their
      role in the decrease of serum cholesterol. BSH proteins play an important role in
      the reduction of cholesterol. This paper adds to a better understanding of BSH
      proteins of intestinal microbes. It gives a great hint that probiotics can be
      used to solve hypercholesterolemia one day.

PMID- 22416716
TI  - Improved determination of D-glucosamine hydrochloride in health foods by HPLC
      using 7-fluoro-4-nitrobenzo-2-oxa-l,3-diazole as a derivative.
AB  - This article presents an improved method to detect D-glucosamine hydrochloride in
      health foods. A simple precolumn derivatization procedure with 7-flouro-4
      nitrobenzo-2-oxa-1,3-diazole (NBD-F) reagent was employed. The separation of the
      derivatized D-glucosamine hydrochloride (NBD-D-glucosamine hydrochloride) was
      performed using a mobile phase consisting of acetonitrile, potassium dihydrogen
      phosphate (0.01 mol/L), and trifluoroacetic acid (350:649.74:0.26, volume ratio)
      at a flow rate of 1.0 mL/min with the column temperature 35  degrees C. Under the
      optimum chromatographic conditions, the peak area of NBD-D-glucosamine
      hydrochloride compared with its absolute value of the peak area of NBD-D
      glucosamine hydrochloride in a standard solution concentration range from 1.0 to
      500.0 mg/L showed a good linear calibration (R = 0.9999). Recoveries, at spiked
      concentrations of 10.0, 40.0, and 500.0 mg/L, varied between 97.2% and 102.6%
      with relative standard deviations ranging from 0.4% to 1.5%. The present method
      provides sufficient sensitivity as reflected by the values of limit of detection
      (LOD) and limit of quantification (LOQ). LOD was determined from the signal-to
      noise ratios (S/N) of NBD-D-glucosamine hydrochloride peak of at least 3 in the
      recovery test at 0.02 mg/L, and the estimated LOQ was 0.06 mg/L (S/N = 10). The
      proposed method was successfully applicable to detect D-glucosamine hydrochloride
      in health foods and drugs containing a variety of complex materials.

PMID- 22416717
TI  - Defining the public health threat of food fraud.
AB  - Food fraud, including the more defined subcategory of economically motivated
      adulteration, is a food risk that is gaining recognition and concern. Regardless
      of the cause of the food risk, adulteration of food is both an industry and a
      government responsibility. Food safety, food fraud, and food defense incidents
      can create adulteration of food with public health threats. Food fraud is an
      intentional act for economic gain, whereas a food safety incident is an
      unintentional act with unintentional harm, and a food defense incident is an
      intentional act with intentional harm. Economically motivated adulteration may be
      just that-economically motivated-but the food-related public health risks are
      often more risky than traditional food safety threats because the contaminants
      are unconventional. Current intervention systems are not designed to look for a
      near infinite number of potential contaminants. The authors developed the core
      concepts reported here following comprehensive research of articles and reports,
      expert elicitation, and an extensive peer review. The intent of this research
      paper is to provide a base reference document for defining food fraud-it focuses
      specifically on the public health threat-and to facilitate a shift in focus from
      intervention to prevention. This will subsequently provide a framework for future
      quantitative or innovative research. The fraud opportunity is deconstructed using
      the criminology and behavioral science applications of the crime triangle and the
      chemistry of the crime. The research provides a food risk matrix and identifies
      food fraud incident types. This project provides a starting point for future food
      science, food safety, and food defense research. PRACTICAL APPLICATION: Food
      fraud, including the more defined subcategory of economically motivated
      adulteration, is a food protection threat that has not been defined or
      holistically addressed. The terrorist attacks of September 11, 2001, led to the
      development of food defense as an autonomous area of study and a new food
      protection discipline. As economically motivated adulteration grows in scope,
      scale, and awareness, it is conceivable that food fraud will achieve the same
      status as an autonomous concept, between food safety and food defense. This
      research establishes a starting point for defining food fraud and identifying the
      public health risks.

PMID- 22416718
TI  - Essential oils and their principal constituents as antimicrobial agents for
      synthetic packaging films.
AB  - Spices and herbal plant species have been recognized to possess a broad spectrum
      of active constituents that exhibit antimicrobial (AM) activity. These active
      compounds are produced as secondary metabolites associated with the volatile
      essential oil (EO) fraction of these plants. A wide range of AM agents derived
      from EOs have the potential to be used in AM packaging systems which is one of
      the promising forms of active packaging systems aimed at protecting food products
      from microbial contamination. Many studies have evaluated the AM activity of
      synthetic AM and/or natural AM agents incorporated into packaging materials and
      have demonstrated effective AM activity by controlling the growth of
      microorganisms. This review examines the more common synthetic and natural AM
      agents incorporated into or coated onto synthetic packaging films for AM
      packaging applications. The focus is on the widely studied herb varieties
      including basil, oregano, and thyme and their EOs.

PMID- 22416719
TI  - Chemical quality of bottled waters: a review.
AB  - Bottled water has become very popular for quenching thirst and as a dietary
      (mineral) supplement. The plethora of natural mineral waters precludes any
      unequivocal system of classification, which makes it difficult for the consumer
      to choose a water with properties that suits him/her exactly. The ever-increasing
      popularity of bottled waters means that it is of the utmost importance to
      determine not only their mineral content, but above all, the content of possible
      contaminants, especially organic ones. In this respect bottled waters are a
      special case, because apart from organic contamination from the environment, the
      water may become secondarily contaminated as a result of its being improperly
      transported and stored. Pesticides, volatile organic compounds, and carbonyl
      compounds have been detected in samples of bottled water. This overview shows the
      available published information on levels of inorganic constituents and organic
      contaminants in samples of bottled water in the context of sample preparation
      procedures and analytical techniques.

PMID- 22416720
TI  - Nutrition-based health: cell-based bioassays for food antioxidant activity
      evaluation.
AB  - Food science has progressively evolved and now there are wide evidences that
      foods have biological activities that are beyond their classical nutritional
      value. In this field, the antioxidant activity of pure compounds, food, feed, and
      dietary supplements has been extensively studied and numerous analytical
      approaches and assay models have been developed, involving various systems from
      simple chemical assays to animal models and human studies. This article is an
      overview of different cell-based models that have been used for testing the
      antioxidant properties of food, feed, and dietary supplements. Advantages,
      drawbacks, and technical problems to develop and validate suitable, robust, and
      high-throughput cell-based bioassays for screening food antioxidant activity will
      be discussed.

PMID- 22416721
TI  - Changes in textural properties of Japanese tenobe somen noodles during storage.
AB  - Tenobe somen (TS) noodles are traditional Japanese wheat-based noodles that are
      produced manually using a sophisticated method called tenobe (literally, "hand
      stretched"). In the tension test, both the tensile strength and extensibility of
      TS noodles were greater than those of machine-made (MS) noodles. In the biting
      test, the chewy texture of TS noodles was realized in the analysis of the force
      deformation curves of each type of somen noodles. The creep test indicated a
      clear difference between the external and internal elasticity of TS noodles. The
      texture of TS noodles appeared to change dramatically during storage in the rainy
      season. In addition, firm and chewy textures of TS noodles stored for 20 mo were
      observed. Similar to the results from our previous study, TS noodles exhibited
      significantly higher dityrosine content than the flour used for their
      manufacture. However, the increase in the dityrosine content during the
      manufacturing process was not observed in the case of MS noodles. Although clear
      textural differences were observed between TS noodles stored for 0 and 20 mo, the
      dityrosine contents of TS noodles at each stage were not largely different.

PMID- 22416722
TI  - Improving functionality of whole egg powder by the addition of gelatine, lactose,
      and pullulan.
AB  - The addition of gelatine (G), lactose (L), pullulan (P), and their mixtures at
      equal ratios (gelatine + lactose [GL] and gelatin + pullulan [GP]) to whole egg
      prior to drying was studied. Their effects on the functional properties (emulsion
      and gelling ability, water holding capacity of gel, foaming, color) and soluble
      protein content of spray dried egg powder during the 6 mo of storage at 20 
      degrees C and 50% relative humidity were investigated. It was demonstrated that
      the emulsion and foaming stability, water holding capacity of gel, and color
      change were significantly affected by the storage time, whereas storage time did
      not affect the strength of gel texture prepared by egg powders. Gelatine and
      pullulan improved the foaming stability and water holding capacity. Lactose
      caused a decrease in emulsion and foaming stability values. The maximum color
      change was observed for the plain egg powder, showing that mixing whole egg with
      carbohydrate- and/or protein-based additives before the drying process preserved
      the color of egg powder. Adding carbohydrate and/or protein caused significant
      changes in functional properties of egg powder.

PMID- 22416723
TI  - Consumer acceptance of ginseng food products.
AB  - Ginseng has been utilized less in food products than in dietary supplements in
      the United States. Sensory acceptance of ginseng food products by U.S. consumers
      has not been reported. The objectives of this study were to: (1) determine the
      sensory acceptance of commercial ginseng food products and (2) assess influence
      of the addition of sweeteners to ginseng tea and ginseng extract to chocolate on
      consumer acceptance. Total of 126 consumers participated in 3 sessions for (1) 7
      commercial red ginseng food products, (2) 10 ginseng teas varying in levels of
      sugar or honey, and (3) 10 ginseng milk or dark chocolates varying in levels of
      ginseng extract. Ginseng candy with vitamin C and ginseng crunchy white chocolate
      were the most highly accepted, while sliced ginseng root product was the least
      accepted among the seven commercial products. Sensory acceptance increased in
      proportion to the content of sugar and honey in ginseng tea, whereas acceptance
      decreased with increasing content of ginseng extract in milk and dark chocolates.
      Findings demonstrate that ginseng food product types with which consumers have
      been already familiar, such as candy and chocolate, will have potential for
      success in the U.S. market. Chocolate could be suggested as a food matrix into
      which ginseng can be incorporated, as containing more bioactive compounds than
      ginseng tea at a similar acceptance level. Future research may include a
      descriptive analysis with ginseng-based products to identify the key drivers of
      liking and disliking for successful new product development.

PMID- 22416724
TI  - Study on classification of soy sauce by electronic tongue technique combined with
      artificial neural network.
AB  - Electronic tongue as an analytical tool coupled with pattern recognition was
      attempted to classify 4 different brands and 2 categories (produced by different
      processes) of Chinese soy sauce. An electronic tongue system was used for data
      acquisition of the samples. Some effective variables were extracted from
      electronic tongue data by principal component analysis (PCA). Backpropagation
      artificial neural network (BP-ANN) was applied to build identification models.
      PCA score plots show an obvious cluster trend of different brands and different
      categories of soy sauce in the 2-dimensional space. The optimal BP-ANN model for
      different brands was achieved when principal components (PCs) were 2, and the
      identification rate of the discrimination model was 100% in both the calibration
      set and the prediction set, and the optimal BP-ANN model for different categories
      had the same result. This work demonstrates that electronic tongue technology
      combined with a suitable pattern recognition method can be successfully used in
      the classification of different brands and categories of soy sauce.

PMID- 22416725
TI  - Using antibrowning agents to enhance quality and safety of fresh-cut avocado
      treated with intense light pulses.
AB  - The effect of antibrowning compounds on the color and firmness of fresh-cut
      avocado treated with intense light pulses (ILP), as well as their impact on the
      survival of Listeria innocua, was investigated in this study. Dipping solutions
      containing 2% (w/v) L-cysteine without ascorbic acid and combined with 1% (w/v)
      citric acid and 1% w/v calcium lactate most effectively preserved the initial
      color and texture of ILP-treated fresh-cut avocado. On the other hand, ILP
      treatments caused a reduction of more than 3 log cycles in the populations of L.
      innocua inoculated on fresh-cut avocado. Log reduction levels increased when
      antibrowning agents were combined with ILP treatments. In conclusion, the use of
      quality-stabilizing agents is a good option to guarantee both the microbiological
      safety of fresh-cut avocado treated with ILP as well as to improve its physical
      and chemical quality. PRACTICAL APPLICATION: Intense light pulses (ILP) have
      received considerable attention during the last years after its approval by the
      U.S. Food and Drug Administration (FDA) in 1996 as a decontamination method for
      food or food surfaces. This article presents relevant information regarding the
      effect of ILP treatments combined with quality-stabilizing compounds as a
      feasible alternative to improve the physical and chemical quality of fresh-cut
      avocado as well as to guarantee its microbiological safety.

PMID- 22416726
TI  - Impact of pre-selected autochthonous starter cultures on the flavor quality of
      Iberian dry-fermented "salchichon" sausage with different ripening processes.
AB  - The purpose of this study was to investigate the impact on flavor quality of 2
      autochthonous starter cultures in the manufacture of Iberian dry-fermented
      "salchichon." A total of 2 strains of Pediococcus acidilactici (MS200 and MS198)
      were combined individually with a strain of Staphylococcus vitulus (RS34) to
      obtain 2 starter cultures: P200S34 and P198S34. The ability of both starter
      cultures to implant during 2 different manufacturing procedures of "salchichon"
      was evaluated by 16S rRNA gene sequence analysis. Changes due to starter culture
      inoculations on volatile compounds were determined by gas chromatography/mass
      spectrometry, and the impact on flavor quality evaluated by sensorial analysis.
      The implantation of starter cultures was adequate and did not significantly
      modify the flavor of the traditional Iberian dry-fermented "salchichon," while
      modulating the volatile compound profile with respect to that found in sausages
      with wild microbial populations. The influence of the starter cultures studied
      was more evident in the shorter sausage processing time. P198S34 was related with
      the increase in some volatile compounds deriving from lipid degradation. P200S34
      contributed to the formation of several volatile compounds arising from lipid
      degradation, amino acid catabolism, and microbial esterase activity. PRACTICAL
      APPLICATION: P200S34 and P198S34 are autochthonous starter cultures for specific
      use in the processing of Iberian dry-fermented sausages. The application of these
      starters allows obtaining Iberian dry-fermented sausages with sensorial
      characteristics standardized. It is greatly interesting for processing and
      marketing industry of these high-quality meat products.

PMID- 22416727
TI  - Sweetness concentration-response behavior of rebiana at room and refrigerator
      temperatures.
AB  - Rebiana is a zero-calorie, natural, high-potency sweetener derived from Stevia
      rebaudiana Bertoni and comprising almost pure rebaudioside A. Reliable
      information on its sweetness concentration-response (C-R) behavior is fundamental
      to rebiana's use as an ingredient. The response curve of rebiana in room
      temperature (21  degrees C) and refrigerated (5  degrees C) water was determined
      using 2-alternative forced choice discrimination tests with a minimum of 70
      tasters. From a series of panels the proportion of tasters finding different
      sucrose concentrations sweeter than a fixed concentration of rebiana was plotted
      against sucrose concentration. The resultant sigmoid curves were linearized by
      transforming the ordinate axis to a probability scale. This aided experimental
      design and determination of isosweet concentrations. The latter were deemed to be
      the sucrose concentration at which 50% of tasters found it to be the sweeter of
      the pair. Isosweet concentrations of sucrose for seven rebiana concentrations up
      to 600 mg/L were used to construct a C-R curve for each temperature. Equations
      were derived for the resultant hyperbolic curves. Rebiana is significantly more
      potent in cold water. PRACTICAL APPLICATION: Rebiana is a new, zero-calorie,
      natural, high-potency sweetener derived from the Stevia plant. We have measured
      the sweetness of rebiana over a range of concentrations at room and refrigerator
      temperatures. This information will help developers of low-calorie products get
      the right sweetness level when replacing sugar with rebiana.

PMID- 22416728
TI  - Ameliorative effect of Grewia tenax (Forssk) fiori fruit extract on CCl(4)
      induced oxidative stress and hepatotoxicity in rats.
AB  - The ethanol extract of Grewia tenax (GTE) fruit was tested for possible efficacy
      against carbon tetrachloride (CCl(4)) induced liver toxicity in Wistar albino
      rats. GTE at doses of 250 and 500 mg/kg were administered orally to CCl(4)
      treated rats. Acute toxicity test and sleeping time determination were done with
      mice. The results showed that oral administration of GTE for 3 wk to rats
      significantly reduced the CCl(4)-induced elevated levels of serum glutamate
      oxaloacetate transaminase, glutamate pyruvate transaminase, gamma-glutamyl
      transferase, alkaline phosphatase, bilirubin, cholesterol, high-density
      lipoproteins, low-density lipoproteins, very low density lipoproteins, and
      triglycerides. Moreover, it was found that the treatment with GTE significantly
      elevated the hemoglobin level in serum and increased the nonprotein sulfhydryl
      and total protein contents in the liver tissue, and a significant diminution was
      observed in the CCl(4)-induced elevated levels of malondialdehyde in the liver
      tissue. The biochemical findings were supported by an evaluation with liver
      histopathology. Pentobarbital-induced prolongation of narcolepsy in mice was
      shortened significantly by the extract. The observed hepatoprotective effect is
      believed to occur due to antioxidant properties of the contents of G. tenax
      extract, which may provide a new drug to be used for fighting liver diseases and
      it validates its folkloric use in anemic and other conditions.

PMID- 22416729
TI  - Comparative study of the hepatoprotective efficacy of Artemisia iwayomogi and
      Artemisia capillaris on ethanol-administered mice.
AB  - We compared the effects of ethylacetate extracts from Artemisia iwayomogi (AIE)
      and Artemisia capillaris (ACE) on ethanol-induced hepatic injury in mice. Ethanol
      (25% v/v, 5 g/kg body weight) was orally administered once a day for 6 wk. AIE or
      ACE was provided in the diet (0.05 g/100 g diet). AIE and ACE did not affect
      hepatic alcohol dehydrogenase activity but did significantly inhibit cytochrome
      P450 2E1 activity. Hepatic acetaldehyde dehydrogenase 2 activity significantly
      increased in the AIE group compared to the control group. AIE caused a
      significant decrease in plasma acetaldehyde levels and aspartate transaminase and
      lactate dehydrogenase activities, whereas ACE slightly decreased these values
      compared to the control. Hepatic catalase activity and glutathione levels were
      significantly increased by AIE and ACE supplements, whereas glutathione
      peroxidase activity was higher only in the AIE group compared to the control
      group. AIE and ACE supplements significantly lowered the plasma cholesterol
      concentration and increased the HDL-cholesterol/total cholesterol ratio compared
      to the control group. Compared to the control, both AIE and ACE groups showed a
      significant decrease in hepatic triglyceride levels and an increase in fecal
      triglyceride excretion simultaneous with inhibition hepatic activities of fatty
      acid synthase, phosphatidate phosphohyrolase, fatty acid beta-oxidation, and
      carnitine palmitoyltransferase. AIE significantly lowered hepatic cholesterol
      levels and increased fecal cholesterol levels compared to the control. These
      results indicate that AIE and ACE exhibit hepatoprotective and hypolipidemic
      properties by enhancing hepatic alcohol, antioxidant, and lipid metabolism. AIE
      seemed to have more potent hepatoprotective effects than ACE.

PMID- 22416730
TI  - Isolation of 3 flavonoids from Mentha longifolia (L.) Hudson subsp. longifolia
      and determination of their genotoxic potentials by using the E. coli WP2 test
      system.
AB  - Flavonoids, abundant in most of plant species, are widely used in medicine and
      development studies on phytotherapeutic drugs due to their various biological
      activities. In the present study, 3 flavonoids, apigenin-7-O-glucoside, apigenin
      7-O-rutinoside, and apigenin-7-O-glucuronide, were isolated from Mentha
      longifolia (L.) Hudson subsp. longifolia by using E. coli WP2 genotoxicity assay
      guided fractionation procedures. Later, the mutagenic and antimutagenic
      properties of each flavonoid were evaluated by using the same genotoxicity assay.
      The results showed that all the test compounds have significant antimutagenic
      activity at tested concentrations with or without S9 activation. The inhibition
      rates were between 25.3% (apigenin-7-O-glucoside with S9-2.0 MUM/plate) and 59.0%
      (apigenin-7-O-rutinoside without S9-2.0 MUM/plate). In conclusion, the results
      revealed that the 3 flavonoids from Mentha longifolia (L.) Hudson subsp.
      longifolia have significant antimutagenic activity, and the findings of the
      present study are valuable for further investigations, focus on the
      phytotherapeutic drug discovery. PRACTICAL APPLICATION: Apigenin derivatives can
      be thought as genetically safe at tested concentrations because they did not show
      mutagenic activity. Furthermore, they have also significant antimutagenic
      activity. These are valuable for further research focus on phytotherapeutic drug
      discovery and development.

PMID- 22416731
TI  - Sandwich enzyme-linked immunosorbent assay (ELISA) for detection of cashew nut in
      foods.
AB  - The presence of undeclared cashew can pose a health risk to cashew-allergic
      consumers. The food industry has the responsibility to declare the presence of
      cashews on packaged foods even when trace residues are or might be present. The
      objective of this study was to develop a rapid, sensitive, and specific enzyme
      linked immunosorbent assay (ELISA) for the detection of cashew residues. Raw and
      roasted cashews were defatted and used separately to immunize sheep, goats, and
      rabbits. The cashew ELISA was developed using sheep and rabbit polyclonal anti
      roasted cashew sera as capture and detector reagents, respectively, with
      visualization through an alkaline phosphatase-mediated substrate reaction. The
      cashew ELISA was shown to have a limit of quantification of 1 ppm (1 MUg
      cashew/g). The ELISA was highly specific except that substantial cross-reactivity
      was noted with pistachio and a lesser degree of cross-reactivity was noted with
      hazelnut. The performance of the ELISA was assessed by manufacturing cookies, ice
      cream, and milk chocolate with added known amounts (0 to 1000 ppm) of cashew. The
      mean percent recoveries for ice cream, cookies, and milk chocolate were 118%+/-
      2.9%, 84.3%+/- 4.0%, and 104%+/- 3.0%, respectively. In a limited retail survey,
      4/5 retail samples with cashew declared on ingredient labels tested positive for
      cashew compared to 5/36 samples of foods with precautionary labels indicating the
      possible presence of one or more tree nuts and 0/18 samples without cashew
      declared on the label in any manner. The cashew ELISA can be used to detect
      undeclared cashew residue in foods and as a potential tool for the food industry
      to assess the effectiveness of allergen control strategies and to guarantee
      compliance with food labeling regulatory requirements.

PMID- 22416733
TI  - Is "thank you" ever enough?

PMID- 22416735
TI  - Unintentional omissions.

PMID- 22416737
TI  - Information needs across the colorectal cancer care continuum: scoping the
      literature.
AB  - Because cancer care requires a multifaceted approach, providing useful and timely
      information to people with colorectal cancer may be fragmented and inconsistent.
      Our interest was in examining what has and has not captured the attention of
      researchers speaking to the information needs of people with colorectal cancer.
      We followed Arksey and O'Malley's framework for the methodology of scoping
      review. Focusing solely on colorectal cancer, we analysed 239 articles to get a
      picture of which information needs and sources of information, as well as the
      timing of providing information, were attended to. Treatment-related information
      received the most mentions (26%). Healthcare professionals (49%) were mentioned
      as the most likely source of information. Among articles focused on one stage of
      the care continuum, post-treatment (survivorship) received the most attention
      (16%). Only 27% of the articles consulted people with colorectal cancer and few
      attended to diet/nutrition and bowel management. This study examined the
      numerical representation of issues to which researchers attend, not the quality
      of the mentions. We ponder, however, on the relationship between the in/frequency
      of mentions and the actual information needs of people with colorectal cancer as
      well as the availability, sources and timing of information.

PMID- 22416738
TI  - Future direction of geriatrics: "gerogeriatrics".

PMID- 22416739
TI  - Dodging the rules, ruling the dodgers.

PMID- 22416740
TI  - Why physicians ought to lie for their patients.
AB  - Sometimes physicians lie to third-party payers in order to grant their patients
      treatment they would otherwise not receive. This strategy, commonly known as
      gaming the system, is generally condemned for three reasons. First, it may hurt
      the patient for the sake of whom gaming was intended. Second, it may hurt other
      patients. Third, it offends contractual and distributive justice. Hence, gaming
      is considered to be immoral behavior. This article is an attempt to show that, on
      the contrary, gaming may sometimes be a physician's duty. Under specific
      circumstances, gaming may be necessary from the viewpoint of the internal
      morality of medicine. Moreover, the objections against gaming are examples of
      what we call the idealistic fallacy, that is, the fallacy of passing judgments in
      a nonideal world according to ideal standards. Hence, the objections are
      inconclusive. Gaming is sometimes justified, and may even be required in the name
      of beneficence.

PMID- 22416741
TI  - Lying to care for patients: Hegelian tragedy or MacIntyrean triumph?

PMID- 22416742
TI  - Honesty is an internal norm of medical practice and the best policy.

PMID- 22416743
TI  - Why physicians should not lie for their patients.

PMID- 22416744
TI  - Doctors are people too.

PMID- 22416746
TI  - Clarifying the nocebo effect and its ethical implications.

PMID- 22416745
TI  - To tell the truth, the whole truth, may do patients harm: the problem of the
      nocebo effect for informed consent.
AB  - The principle of informed consent obligates physicians to explain possible side
      effects when prescribing medications. This disclosure may itself induce adverse
      effects through expectancy mechanisms known as nocebo effects, contradicting the
      principle of nonmaleficence. Rigorous research suggests that providing patients
      with a detailed enumeration of every possible adverse event-especially subjective
      self-appraised symptoms-can actually increase side effects. Describing one
      version of what might happen (clinical "facts") may actually create outcomes that
      are different from what would have happened without this information (another
      version of "facts"). This essay argues that the perceived tension between
      balancing informed consent with nonmaleficence might be resolved by recognizing
      that adverse effects have no clear black or white "truth." This essay suggests a
      pragmatic approach for providers to minimize nocebo responses while still
      maintaining patient autonomy through "contextualized informed consent," which
      takes into account possible side effects, the patient being treated, and the
      particular diagnosis involved.

PMID- 22416747
TI  - Nocebo and informed consent in the internet era.

PMID- 22416748
TI  - Saying things the "right" way: avoiding "nocebo" effects and providing full
      informed consent.

PMID- 22416749
TI  - Plenty to worry about: consent, control, and anxiety.

PMID- 22416750
TI  - Ulysses contracts and the nocebo effect.

PMID- 22416754
TI  - De minimis risk proposal offers little to current approach.

PMID- 22416755
TI  - Preschoolers acquire general knowledge by sharing in pretense.
AB  - Children acquire general knowledge about many kinds of things, but there are few
      known means by which this knowledge is acquired. In this article, it is proposed
      that children acquire generic knowledge by sharing in pretend play. In Experiment
      1, twenty-two 3- to 4-year-olds watched pretense in which a puppet represented a
      "nerp" (an unfamiliar kind of animal). For instance, in one scenario, the nerp
      ate and disliked a carrot. When subsequently asked generic questions about real
      nerps, children's responses suggested that they had learned general facts (e.g.,
      nerps dislike carrots). In Experiment 2, thirty-two 4- to 5-year-olds learned
      from scenarios lacking pretend speech or sound effects. The findings reveal a
      long overlooked means by which children can acquire generic knowledge.

PMID- 22416756
TI  - OBIF, an osteoblast induction factor, plays an essential role in bone formation
      in association with osteoblastogenesis.
AB  - In vertebrate bone formation, the functional mechanisms of transcription factors
      in osteoblastic differentiation have been relatively well elucidated; however,
      the exact roles of cell-extrinsic molecules are less clear. We previously
      identified human and mouse Obif, an osteoblast induction factor, also known as
      Tmem119, which encodes a single transmembrane protein. OBIF is predominantly
      expressed in osteoblasts in mouse. While exogenous Obif expression stimulated
      osteoblastic differentiation, knockdown of Obif inhibits the osteoblastic
      differentiation of pre-osteoblastic MC3T3-E1 cells. In order to investigate an in
      vivo role of OBIF in bone formation, we generated Obif-deficient mice by targeted
      gene disruption. Analyses of micro-computed tomography (mCT) revealed that Obif(
      /-) mice exhibit significantly reduced cortical thickness in the mid-shaft of the
      femur at postnatal day 14 (P14). Furthermore, progressive bone hypoplasia is
      observed after 8 weeks. The expression levels of osteoblast marker genes,
      Collagen 1a1, Osteopontin, Runx2, and Osterix, in the calvaria were decreased in
      Obif(-/-) mice at P4. These data indicate that Obif plays an essential role in
      bone formation through regulating osteoblastogenesis.

PMID- 22416757
TI  - The mid-M1 segment of the middle cerebral artery is a cutoff clot location for
      good outcome in intravenous thrombolysis.
AB  - BACKGROUND AND PURPOSE: We studied the impact of the location of the thrombus
      (internal carotid artery, proximal M1 segment, distal M1 segment, M2 segment, and
      M3 segment of the middle cerebral artery) in predicting the clinical outcome of
      patients treated with intravenous thrombolytic therapy (<3 h) in a retrospective
      cohort. METHODS: Anterior circulation thrombus was detected with computed
      tomography angiography in 105 patients. Baseline clinical and radiological
      information was collected and entered into logistic regression analysis to
      predict favorable clinical outcome (3-month modified Rankin Scale from 0 to 2 was
      a primary outcome measure). RESULTS: Three months after stroke, there was a
      significant increase in mortality (32% vs. 3%, P < 0.001) and functional
      dependency (82% vs. 29%, P < 0.001) in patients with internal carotid artery or
      proximal M1 segment of the middle cerebral artery thrombus compared to a more
      distal occlusion. In the regression analysis, after adjusting for National
      Institutes of Health Stroke Scale, age, sex, and onset-to-treatment time, the
      clot location was an independent predictor of good clinical outcome (P = 0.001)
      and exhibited dose-response type behavior when moving from a proximal vessel
      position to a more distal one. When the location was dichotomized, a cutoff
      between the proximal and the distal M1 segments best differentiated between good
      and poor clinical outcome (OR = 16.0, 95% CI 3.9-66.2). CONCLUSIONS: The outcome
      of acute internal carotid artery or proximal M1 segment of the middle cerebral
      artery occlusion is generally poor even if treated with intravenous thrombolysis.
      Alternative revascularization strategies should be considered. Vascular imaging
      at the admission is required to guide this decision.

PMID- 22416758
TI  - Mpg2 interacts and cooperates with Mpg1 to maintain yeast glycosylation.
AB  - Using a yeast two-hybrid screen, we isolated a gene from Schizosaccharomyces
      pombe, whose product interacts with Mpg1, a GDP-mannose-1-phosphate
      guanylyltransferase involved in the maintenance of cell wall integrity and
      glycosylation. We have designated this gene mpg2 based on its similarity to Mpg1.
      Mpg2 is evolutionarily conserved in higher eukaryotes. In the absence of Mpg2,
      defects in cell growth and sensitivity to hygromycin B are observed. When mpg1 is
      depleted, the lack of mpg2 causes a synthetic enhancement of the growth defect,
      the sensitivity to hygromycin B and the cell cycle phenotype previously reported
      for mpg1 mutant. Finally, Mpg1 overexpression complements the Deltampg2 mutant
      phenotypes. Taken together, these results indicate that mpg1 and mpg2 function
      together in glycosylation and septum formation.

PMID- 22416760
TI  - Polystyrene-supported (2S)-(-)-3-exo-piperazinoisoborneol: an efficient catalyst
      for the batch and continuous flow production of enantiopure alcohols.
AB  - A polystyrene-supported analog (PS-PIB) of 3-exo-morpholinoisoborneol (MIB),
      designed for increased chemical stability, has been synthesized and used as a
      ligand in the asymmetric alkylation of aldehydes with Et(2)Zn. The supported
      ligand turned out to be highly active and enantioselective for a broad scope of
      substrates (92-99% ee), allowing repeated recycling. A single-pass, continuous
      flow process implemented with PS-PIB shows only a marginal decrease in conversion
      after 30 h of operation.

PMID- 22416759
TI  - Luciferase-based assay for adenosine: application to S-adenosyl-L-homocysteine
      hydrolase.
AB  - S-Adenosyl-L-homocysteine hydrolase (SAHH) catalyzes the reversible conversion of
      S-adenosyl-L-homocysteine (SAH) to adenosine (ADO) and L-homocysteine, promoting
      methyltransferase activity by relief of SAH inhibition. SAH catabolism is linked
      to S-adenosylmethionine metabolism, and the development of SAHH inhibitors is of
      interest for new therapeutics with anticancer or cholesterol-lowering effects. We
      have developed a continuous enzymatic assay for adenosine that facilitates high
      throughput analysis of SAHH. This luciferase-based assay is 4000-fold more
      sensitive than former detection methods and is well suited for continuous
      monitoring of ADO formation in a 96-well-plate format. The high-affinity
      adenosine kinase from Anopheles gambiae efficiently converts adenosine to
      adenosine monophosphate (AMP) in the presence of guanosine triphosphate. AMP is
      converted to adenosine triphosphate and coupled to firefly luciferase. With this
      procedure, kinetic parameters (K(m), k(cat)) for SAHH were obtained, in good
      agreement with literature values. Assay characteristics include sustained light
      output combined with ultrasensitive detection (10(-7) unit of SAHH). The assay is
      documented with the characterization of slow-onset inhibition for inhibitors of
      the hydrolase. Application of this assay may facilitate the development of SAHH
      inhibitors and provide an ultrasensitive detection for the formation of adenosine
      from other biological reactions.

PMID- 22416761
TI  - N-heterocyclic phosphenium ligands as sterically and electronically-tunable
      isolobal analogues of nitrosyls.
AB  - The coordination chemistry of an N-heterocyclic phosphenium (NHP)-containing
      bis(phosphine) pincer ligand has been explored with Pt(0) and Pd(0) precursors.
      Unlike previous compounds featuring monodentate NHP ligands, the resulting NHP Pt
      and Pd complexes feature pyramidal geometries about the central phosphorus atom,
      indicative of a stereochemically active lone pair. Structural, spectroscopic, and
      computational data suggest that the unusual pyramidal NHP geometry results from
      two-electron reduction of the phosphenium ligand to generate transition metal
      complexes in which the Pt or Pd centers have been formally oxidized by two
      electrons. Interconversion between planar and pyramidal NHP geometries can be
      affected by either coordination/dissociation of a two-electron donor ligand or
      two-electron redox processes, strongly supporting an isolobal analogy with the
      linear (NO(+)) and bent (NO(-)) variations of nitrosyl ligands. In contrast to
      nitrosyls, however, these new main group noninnocent ligands are sterically and
      electronically tunable and are amenable to incorporation into chelating ligands,
      perhaps representing a new strategy for promoting redox transformations at
      transition metal complexes.

PMID- 22416762
TI  - Complement activation and cell uptake responses toward polymer-functionalized
      protein nanocapsules.
AB  - Self-assembling protein nanocapsules can be engineered for various
      bionanotechnology applications. Using the dodecahedral scaffold of the E2 subunit
      from pyruvate dehydrogenase, we introduced non-native surface cysteines for site
      directed functionalization. The modified nanoparticle's structural, assembly, and
      thermostability properties were comparable to the wild-type scaffold (E2-WT), and
      after conjugation of poly(ethylene glycol) (PEG) to these cysteines, the
      nanoparticle remained intact and stable up to 79.7 +/- 1.8  degrees C. PEGylation
      of particles reduced uptake by human monocyte-derived macrophages and MDA-MB-231
      breast cancer cells, with decreased uptake as PEG chain length is increased. In
      vitro C4-depletion and C5a-production assays yielded 97.6 +/- 10.8% serum C4
      remaining and 40.1 +/- 6.0 ng/mL C5a for E2-WT, demonstrating that complement
      activation is weak for non-PEGylated E2 nanoparticles. Conjugation of PEG to
      these particles moderately increased complement response to give 79.7 +/- 6.0% C4
      remaining and 87.6 +/- 10.1 ng/mL C5a. Our results demonstrate that PEGylation of
      the E2 protein nanocapsules can modulate cellular uptake and induce low levels of
      complement activation, likely via the classical/lectin pathways.

PMID- 22416764
TI  - Evolution of Bacillus subtilis to enhanced growth at low pressure: up-regulated
      transcription of des-desKR, encoding the fatty acid desaturase system.
AB  - The atmospheric pressure on Mars ranges from 1-10 mbar, about 1% of Earth
      pressure (~1013 mbar). Low pressure is a growth-inhibitory factor for terrestrial
      microorganisms on Mars, and a putative low-pressure barrier for growth of Earth
      bacteria of ~25 mbar has been postulated. In a previous communication, we
      described the isolation of a strain of Bacillus subtilis that had evolved
      enhanced growth ability at the near-inhibitory low pressure of 50 mbar. To
      explore mechanisms that enabled growth of the low-pressure-adapted strain,
      numerous genes differentially transcribed between the ancestor strain WN624 and
      low-pressure-evolved strain WN1106 at 50 mbar were identified by microarray
      analysis. Among these was a cluster of three candidate genes (des, desK, and
      desR), whose mRNA levels in WN1106 were higher than the ancestor on the
      microarrays. Up-regulation of these genes was confirmed by quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR) analysis. The des, desK, and
      desR genes encode the Des membrane fatty acid (FA) desaturase, the DesK sensor
      kinase, and the DesR response regulator, respectively, which function to maintain
      membrane fluidity in acute response to temperature downshift. Pressure downshift
      caused an up-regulation of des mRNA levels only in WN1106, but expression of a
      des-lacZ transcriptional fusion was unaffected, which suggests that des
      regulation was different in response to temperature versus pressure downshift.
      Competition experiments showed that inactivation of the des gene caused a slight,
      but statistically significant, loss of fitness of strain WN1106 at 50 mbar.
      Further, analysis of membrane FA composition of cells grown at 1013 versus 50
      mbar revealed a decrease in the ratio of unsaturated to saturated FAs but an
      increase in the ratio of anteiso- to iso-FAs. The present study represents a
      first step toward identification of molecular mechanisms by which B. subtilis
      could sense and respond to the novel environmental stress of low pressure.

PMID- 22416763
TI  - Quantitative analysis of the detergent-insoluble brain proteome in frontotemporal
      lobar degeneration using SILAC internal standards.
AB  - A hallmark of neurodegeneration is the aggregation of disease related proteins
      that are resistant to detergent extraction. In the major pathological subtype of
      frontotemporal lobar degeneration (FTLD), modified TAR-DNA binding protein 43
      (TDP-43), including phosphorylated, ubiquitinated, and proteolytically cleaved
      forms, is enriched in detergent-insoluble fractions from post-mortem brain
      tissue. Additional proteins that accumulate in the detergent-insoluble FTLD brain
      proteome remain largely unknown. In this study, we used proteins from stable
      isotope-labeled (SILAC) human embryonic kidney 293 cells (HEK293) as internal
      standards for peptide quantitation across control and FTLD insoluble brain
      proteomes. Proteins were identified and quantified by liquid-chromatography
      coupled with tandem mass spectrometry (LC-MS/MS) and 21 proteins were determined
      to be enriched in FTLD using SILAC internal standards. In parallel, label-free
      quantification of only the unlabeled brain derived peptides by spectral counts
      (SC) and G-test analysis identified additional brain-specific proteins
      significantly enriched in disease. Several proteins determined to be enriched in
      FTLD using SILAC internal standards were not considered significant by G-test due
      to their low total number of SC. However, immunoblotting of FTLD and control
      samples confirmed enrichment of these proteins, highlighting the utility of SILAC
      internal standard to quantify low-abundance proteins in brain. Of these, the RNA
      binding protein PTB-associated splicing factor (PSF) was further characterized
      because of structural and functional similarities to TDP-43. Full-length PSF and
      shorter molecular weight fragments, likely resulting from proteolytic cleavage,
      were enriched in FTLD cases. Immunohistochemical analysis of PSF revealed
      predominately nuclear localization in control and FTLD brain tissue and was not
      associated with phosphorylated pathologic TDP-43 neuronal inclusions. However, in
      a subset of FTLD cases, PSF was aberrantly localized to the cytoplasm of
      oligodendrocytes. These data raise the possibility that PSF directed RNA
      processes in oligodendrocytes are altered in neurodegenerative disease.

PMID- 22416765
TI  - Effects of glial cell line-derived neurotrophic factor intrathecal injection on
      spinal dorsal horn glial fibrillary acidic protein expression in a rat model of
      neuropathic pain.
AB  - Glial fibrillary acidic protein (GFAP) is a specific astrocytic marker in the
      central nervous system. Few studies on the effects of glial cell line-derived
      neurotrophic factor (GDNF) intrathecal injection on GFAP expression exist in the
      literature. The present study determined GFAP expression in rat spinal dorsal
      horn following a spinal nerve ligation (SNL). The effects of GDNF intrathecal
      injection on GFAP expression were examined to gather experimental evidence on the
      mechanisms underlying neuropathic pain. Following L5-6 SNL, male Sprague-Dawley
      rats were randomly divided into four groups: normal control, sham-operated, SNL,
      and GDNF. Each group was further divided into three subgroups (n = 10) according
      to the times of sacrifice: 3, 7, and 14 days after surgery. Compared with the
      normal control and the sham-operated groups, GFAP expression in the SNL group
      increased at day 3 after surgery and lasted until 14 days after. GFAP expression
      was significantly less in the GDNF group compared with the SNL group which lasted
      until 14 days after surgery, suggesting that rat spinal dorsal horn GFAP
      expression contributes to SNL-induced neuropathic pain. The mechanisms underlying
      GDNF alleviation of neuropathic pain were shown to be related to the GDNF
      inhibition of GFAP expression in the spinal dorsal horn.

PMID- 22416766
TI  - Lay understandings of defence mechanisms: the role of personality traits and
      gender.
AB  - This study looks at lay people's knowledge and use of the defence mechanisms. It
      focused on 21 of the better known "Freudian" defence mechanisms. A total of 208
      participants (73 males and 135 females) completed a questionnaire regarding their
      knowledge and reported personal use of 21 defence mechanisms and a short
      personality test. Participants were required to state (1) whether they had heard
      of each mechanism, (2) how common they believed it to be and (3) whether they
      themselves used each of them. The defences were categorised into four levels:
      Pathological, immature, neurotic and mature. Two personality traits (Openness and
      Neuroticism) positively correlated with two of the levels but few gender or age
      correlations were identified. Regression analysis showed that Neuroticism
      predicted the three less mature defence levels; Gender was a contributing
      predictor of a pathological defence style and Openness and religiosity combined
      with Neuroticism predicted an immature defence style. Participants admitted using
      the more socially acceptable (mature) defences (i.e. humour, intellectualisation)
      than the less acceptable (pathological) defences (i.e. distortion,
      hypochondriasis). Implications for psychotherapy are discussed and the
      limitations of the study considered.

PMID- 22416767
TI  - A method to improve electrical properties of BiFeO3 thin films.
AB  - A method is used to improve the electrical properties of BiFeO(3) thin films by
      modifying the Bi content in ceramic targets, where all thin films were prepared
      on SrRuO(3)/Pt/TiO(2)/SiO(2)/Si(100) substrates by radio frequency sputtering.
      The Bi content in the ceramic target strongly affects the electrical properties
      of BiFeO(3) thin films. BiFeO(3) thin films prepared by using the ceramic target
      of Bi/Fe ~ 1.15 with a molar ratio demonstrate a low leakage current density and
      a low dielectric loss. Moreover, a larger remanent polarization of 2P(r) ~ 167.6
      MUC/cm(2) is also demonstrated for the BiFeO(3) thin films prepared by using the
      ceramic target of Bi/Fe ~ 1.15, together with an improved fatigue behavior.
      Therefore, it is an effective way to improve the electrical properties of bismuth
      ferrite thin films by modifying the Bi content in ceramic targets.

PMID- 22416768
TI  - Metabolic syndrome prevalence is increased in rheumatoid arthritis patients and
      is associated with disease activity.
AB  - OBJECTIVES: To evaluate the prevalence of metabolic syndrome (MetS) in patients
      with rheumatoid arthritis (RA) vs. controls, and to verify possible associations
      of MetS with specific disease-related factors. METHODS: The subjects were 283 RA
      patients and 226 healthy controls, frequency matched by age and sex. MetS was
      defined according to National Cholesterol Education Program (NCEP) criteria.
      Disease activity was evaluated with the Disease Activity Score using 28 joints
      (DAS28). A standardized clinical evaluation was performed and cardiovascular risk
      factors were assessed. RESULTS: The criteria for MetS were met by 39.2% RA
      patients vs. 19.5% in the control group (p < 0.001). Increased waist
      circumference, elevated blood pressure (BP), and fasting glucose were more
      frequent in RA patients than controls (p < 0.001 for all associations). By
      multiple logistic regression analysis (adjusted for age, sex, and years at
      school), the risk of having MetS was significantly higher for RA patients than
      for controls [odds ratio (OR) 1.87, 95% confidence interval (CI) 1.17-3.00, p =
      0.009]. The DAS28 was significantly higher in RA patients with MetS than in those
      without MetS (3.59 +/- 1.27 vs. 3.14 +/- 1.53; p = 0.01). Disease duration, the
      presence of rheumatoid factor, and extra-articular manifestations were similar
      for patients with and without MetS. CONCLUSIONS: MetS frequency was higher in RA
      patients than in controls. Among RA patients, MetS was associated with disease
      activity. The higher prevalence of cardiovascular risk factors in RA suggests
      that inflammatory processes play a notable role in the development of
      cardiovascular disease (CVD), and indicates that tight control of systemic
      inflammatory activity and CVD modifiable risk factors should be recommended.

PMID- 22416770
TI  - Systematic prioritization of cancer combination therapies: are we really on
      target?

PMID- 22416772
TI  - The impact of CDK inhibition in human malignancies associated with pronounced
      defects in apoptosis: advantages of multi-targeting small molecules.
AB  - Malignant cells in chronic lymphocytic leukemia (CLL) and related diseases are
      heterogeneous and consist primarily of long-lived resting cells in the periphery
      and a minor subset of dividing cells in proliferating centers. Both cell
      populations have different molecular signatures that play a major role in
      determining their sensitivity to therapy. Contemporary approaches to treating CLL
      are heavily reliant on cytotoxic chemotherapeutics. However, none of the current
      treatment regimens can be considered curative. Pharmacological CDK inhibitors
      have extended the repertoire of potential drugs for CLL. Multi-targeted CDK
      inhibitors affect CDKs involved in regulating both cell cycle progression and
      transcription. Their interference with transcriptional elongation represses anti
      apoptotic proteins and, thus, promotes the induction of apoptosis. Importantly,
      there is evidence that treatment with CDK inhibitors can overcome resistance to
      therapy. The pharmacological CDK inhibitors have great potential for use in
      combination with other therapeutics and represent promising tools for the
      development of new curative treatments for CLL.

PMID- 22416773
TI  - Current limitations and future opportunities for epigenetic therapies.
AB  - This article reviews progress in epigenetic therapies that hope to improve the
      treatment of cancer. Tumors show widespread, aberrant epigenetic changes, leading
      to changes in the expression of genes involved in all the hallmarks of cancer.
      These epigenetic changes can potentially be reversed using small-molecule
      inhibitors of enzymes involved in maintenance of the epigenetic state. DNA
      demethylating agents and histone deacetylase inhibitors have shown anti-tumor
      activity against certain hematological malignancies; however, their activity in
      solid tumors remains more uncertain. Major challenges remain in delivery of
      epigenetic therapy, maintenance of a pharmacodynamic response and achievement of
      a therapeutic index. We believe histone lysine methyl transferases are a highly
      promising epigenetic target, which has yet to be clinically exploited.
      Crystallographic studies on histone lysine methyl transferases provide insights
      into their mechanism and specificity crucial for the design and development of
      small-molecule inhibitors.

PMID- 22416775
TI  - HDAC inhibitors for the treatment of cutaneous T-cell lymphomas.
AB  - Epigenetic modification by small-molecule histone deacetylase inhibitors (HDAC
      Is) has been a promising new antineoplastic approach for various solid and
      hematological malignancies, particularly for cutaneous T-cell lymphoma (CTCL).
      Vorinostat, a pan-HDAC-I and, most recently, romidepsin, a bicyclic pan-HDAC-I,
      have been US FDA approved for treatment of relapsed or refractory CTCL. However,
      because many patients do not reach the 50% partial response mark and response is
      not always sustainable, overcoming HDAC-I resistance by adding other agents or
      finding more selective molecules is an important clinical problem in realizing
      the full clinical potential of HDAC-Is. In this review, we discuss the molecular
      basis for HDAC-I function in cancer, the clinical response and side-effect
      profile experienced by CTCL patients, and the progress made in attempting to
      identify biomarkers of response and resistance, as well as synergistic
      combination therapies.

PMID- 22416776
TI  - mTOR kinase inhibitors as a treatment strategy in hematological malignancies.
AB  - The mammalian target of rapamycin (mTOR) kinase is a key element of intracellular
      signal transduction, responsible for the regulation of cell growth and
      proliferation. Since abnormal activation of the mTOR pathway was found in several
      tumors, including human malignancies, it may be an attractive target for
      antineoplastic treatment. The first identified mTOR inhibitor was rapamycin
      (sirolimus). Subsequently, the most potent rapamycin analogues (rapalogues), such
      as everolimus, temsirolimus and deforolimus, have been developed. After
      encouraging preclinical experiments, several clinical trials testing the
      rapalogues in monotherapy or in combinations with other cytotoxic agents have
      been conducted in patients with hematological malignancies. Results of these
      studies, described in this review, indicate that inhibition of the mTOR pathway
      may be a very promising strategy of anti-tumor treatment in several types of
      lymphomas and leukemias. Recently, a second generation of more effective mTOR
      inhibitors has been developed. These are currently being assessed in preclinical,
      Phase I or I/II clinical studies.

PMID- 22416774
TI  - EGFR/HER-targeted therapeutics in ovarian cancer.
AB  - Despite decades of research and evolving treatment modalities, survival among
      patients with epithelial ovarian cancer has improved only incrementally. During
      this same period, the development of biologically targeted therapeutics has
      improved survival for patients with diverse malignancies. Many of these new drugs
      target the human epidermal growth factor receptor (EGFR/HER/ErbB) family of
      tyrosine kinases, which play a major role in the etiology and progression of many
      carcinomas, including epithelial ovarian cancer. While several HER-targeted
      therapeutics are US FDA approved for the treatment of various malignancies, none
      have gained approval for the treatment of ovarian cancer. Here, we review the
      published literature on HER-targeted therapeutics for the treatment of ovarian
      cancer, including novel HER-targeted therapeutics in various stages of clinical
      development, as well as the challenges that have limited the use of these
      inhibitors in clinical settings.

PMID- 22416779
TI  - Recent advances in developing synthetic carbohydrate-based vaccines for cancer
      immunotherapies.
AB  - Cancer cells can often be distinguished from healthy cells by the expression of
      unique carbohydrate sequences decorating the cell surface as a result of aberrant
      glycosyltransferase activity occurring within the cell; these unusual
      carbohydrates can be used as valuable immunological targets in modern vaccine
      designs to raise carbohydrate-specific antibodies. Many tumor antigens (e.g.,
      GM2, Le(y), globo H, sialyl Tn and TF) have been identified to date in a variety
      of cancers. Unfortunately, carbohydrates alone evoke poor immunogenicity, owing
      to their lack of ability in inducing T-cell-dependent immune responses. In order
      to enhance their immunogenicity and promote long-lasting immune responses,
      carbohydrates are often chemically modified to link to an immunogenic protein or
      peptide fragment for eliciting T-cell-dependent responses. This review will
      present a summary of efforts and advancements made to date on creating
      carbohydrate-based anticancer vaccines, and will include novel approaches to
      overcoming the poor immunogenicity of carbohydrate-based vaccines.

PMID- 22416777
TI  - Targeted cancer therapy: giving histone deacetylase inhibitors all they need to
      succeed.
AB  - Histone deacetylase inhibitors (HDACis) have now emerged as a powerful new class
      of small-molecule therapeutics acting through the regulation of the acetylation
      states of histone proteins (a form of epigenetic modulation) and other non
      histone protein targets. Over 490 clinical trials have been initiated in the last
      10 years, culminating in the approval of two structurally distinct HDACis - SAHA
      (vorinostat, ZolinzaTM) and FK228 (romidepsin, IstodaxTM). However, the current
      HDACis have serious limitations, including ineffectively low concentrations in
      solid tumors and cardiac toxicity, which is hindering their progress in the
      clinic. Herein, we review the primary paradigms being pursued to overcome these
      hindrances, including HDAC isoform selectivity, localized administration, and
      targeting cap groups to achieve selective tissue and cell type distribution.

PMID- 22416778
TI  - Targeting the ubiquitin-proteasome pathway with inorganic compounds to fight
      cancer: a challenge for the future.
AB  - Proteasomes are large multicatalytic complexes endowed with proteinase activity,
      located both in the cytosol and in the nucleus of eukaryotic cells. The ubiquitin
      proteasome system is responsible for selective degradation of most intracellular
      proteins and therefore plays an essential regulatory role in many critical
      cellular processes. The proteasomal activity can also contribute to the
      pathological states of many diseases, including inflammation, neurodegeneration
      and cancer, through a disregulation in the level of regulatory proteins. These
      diseases may be targeted by modulating components of the ubiquitin-proteasome
      pathway, using small molecules as inhibitors. Bortezomib (Velcade((r))), used for
      the treatment of relapsed multiple myeloma, is the first and, up to now, the only
      proteasome inhibitor approved by the US FDA. Nowadays, the discovery that some
      metal-based complexes exert their antiproliferative action by affecting
      proteasomal activities provides the possibility of developing new opportunities
      in cancer therapy.

PMID- 22416781
TI  - Comparison of resistance mutation patterns in historical plasma HIV RNA genotypes
      with those in current proviral HIV DNA genotypes among extensively treated
      patients with suppressed replication.
AB  - OBJECTIVES: Heavily treatment-experienced patients with good virological control
      could be at risk of virological failure on switching to a new regimen if pre
      existing drug resistance is not taken into account. We examined whether
      genotyping based on cellular HIV-1 DNA during controlled viraemia identifies
      resistance mutations detected in plasma HIV-1 RNA during treatment with previous
      antiretroviral regimens. PATIENTS AND METHODS: All 169 patients enrolled in the
      Agence Nationale de Recherche sur le SIDA (ANRS) 138-intEgrase inhibitor MK_0518
      to Avoid Subcutaneous Injections of EnfuviRtide (EASIER) trial had already
      received three antiretroviral drug classes [nucleoside reverse transcriptase
      inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI) and
      protease inhibitor (PI)] and had plasma HIV-1 RNA<400 copies/ml at baseline. The
      results of previous resistance genotyping of plasma HIV-1 RNA in individual
      patients were compared with those of resistance genotyping of whole-blood HIV-1
      DNA at randomization. RESULTS: A median of 4 plasma RNA genotypes were available
      for the 169 patients. The median numbers of resistance mutations in HIV-1 RNA and
      DNA were, respectively, 5 and 4 for NRTIs, 2 and 1 for NNRTIs, and 10 and 8 for
      PIs. The difference was significant for all three drug classes (P=0.001).
      Resistance to at least one antiretroviral drug was detected exclusively in HIV-1
      RNA or in DNA in 63% and 13% of patients for NRTI, 47% and 1% of patients for
      NNRTI, and 50% and 7% of patients for PI, respectively. CONCLUSION: This study
      shows that, among highly treatment-experienced patients on effective highly
      active antiretroviral therapy, resistance genotyping of HIV-1 DNA detects fewer
      resistance mutations than previous analyses of HIV-1 RNA. These results have
      implications for patient management and for the design of switch studies.

PMID- 22416782
TI  - Effects of homosynaptic depression on spectral properties of H-reflex recordings.
AB  - The purpose of this study was to determine the effects of homosynaptic depression
      (HD) on spectral properties of the soleus (SOL) H-reflex. Paired stimulations,
      separated by 100 ms, were used to elicit an unconditioned and conditioned H
      reflex in the SOL muscle of 20 participants during quiet standing. Wavelet and
      principal component analyses were used to analyze features of the time-varying
      spectral properties of the unconditioned and conditioned H-reflex. The effects of
      HD on spectral properties of the H-reflex signal were quantified by comparing
      extracted principal component scores. The analysis extracted two principal
      components: one associated with the intensity of the spectra and one associated
      with its frequency. The scores for both principal components were smaller for the
      conditioned H-reflex. HD decreases the spectral intensity and changes the
      spectral frequency of H-reflexes. These results suggest that HD changes the
      recruitment pattern of the motor units evoked during H-reflex stimulations, in
      that it not only decreases the intensity, but also changes the types of motor
      units that contribute to the H-reflex signal.

PMID- 22416783
TI  - Helium ion microscopy for high-resolution visualization of the articular
      cartilage collagen network.
AB  - The articular cartilage collagen network is an important research focus because
      network disruption results in cartilage degeneration and patient disability. The
      recently introduced helium ion microscope (HIM), with its smaller probe size,
      longer depth of field and charge neutralization, has the potential to overcome
      the inherent limitations of electron microscopy for visualization of collagen
      network features, particularly at the nanoscale. In this study, we evaluated the
      capabilities of the helium ion microscope for high-resolution visualization of
      the articular cartilage collagen network. Images of rabbit knee cartilage were
      acquired with a helium ion microscope; comparison images were acquired with a
      field emission scanning electron microscope (FE-SEM) and a transmission electron
      microscope (TEM). Sharpness of example high-resolution helium ion microscope and
      field emission scanning electron microscope images was quantified using the 25
      75% rise distance metric. The helium ion microscope was able to acquire high
      resolution images with unprecedented clarity, with greater sharpness and three
      dimensional-like detail of nanoscale fibril morphologies and fibril connections,
      in samples without conductive coatings. These nanoscale features could not be
      resolved by field emission scanning electron microscopy, and three-dimensional
      network structure could not be visualized with transmission electron microscopy.
      The nanoscale three-dimensional-like visualization capabilities of the helium ion
      microscope will enable new avenues of investigation in cartilage collagen network
      research.

PMID- 22416784
TI  - Addressing indigenous health workforce inequities: a literature review exploring
      'best' practice for recruitment into tertiary health programmes.
AB  - INTRODUCTION: Addressing the underrepresentation of indigenous health
      professionals is recognised internationally as being integral to overcoming
      indigenous health inequities. This literature review aims to identify 'best
      practice' for recruitment of indigenous secondary school students into tertiary
      health programmes with particular relevance to recruitment of Maori within a New
      Zealand context. METHODOLOGY/METHODS: A Kaupapa Maori Research (KMR)
      methodological approach was utilised to review literature and categorise content
      via: country; population group; health profession focus; research methods;
      evidence of effectiveness; and discussion of barriers. Recruitment activities are
      described within five broad contexts associated with the recruitment pipeline:
      Early Exposure, Transitioning, Retention/Completion, Professional Workforce
      Development, and Across the total pipeline. RESULTS: A total of 70 articles were
      included. There is a lack of published literature specific to Maori recruitment
      and a limited, but growing, body of literature focused on other indigenous and
      underrepresented minority populations.The literature is primarily descriptive in
      nature with few articles providing evidence of effectiveness. However, the
      literature clearly frames recruitment activity as occurring across a pipeline
      that extends from secondary through to tertiary education contexts and in some
      instances vocational (post-graduate) training. Early exposure activities
      encourage students to achieve success in appropriate school subjects, address
      deficiencies in careers advice and offer tertiary enrichment opportunities.
      Support for students to transition into and within health professional programmes
      is required including bridging/foundation programmes, admission policies/quotas
      and institutional mission statements demonstrating a commitment to achieving
      equity. Retention/completion support includes academic and pastoral interventions
      and institutional changes to ensure safer environments for indigenous students.
      Overall, recruitment should reflect a comprehensive, integrated pipeline approach
      that includes secondary, tertiary, community and workforce stakeholders.
      CONCLUSIONS: Although the current literature is less able to identify 'best
      practice', six broad principles to achieve success for indigenous health
      workforce development include: 1) Framing initiatives within indigenous
      worldviews 2) Demonstrating a tangible institutional commitment to equity 3)
      Framing interventions to address barriers to indigenous health workforce
      development 4) Incorporating a comprehensive pipeline model 5) Increasing family
      and community engagement and 6) Incorporating quality data tracking and
      evaluation. Achieving equity in health workforce representation should remain
      both a political and ethical priority.

PMID- 22416786
TI  - Task-related enhancement in corticomotor excitability during haptic sensing with
      the contra- or ipsilateral hand in young and senior adults.
AB  - BACKGROUND: Haptic sensing with the fingers represents a unique class of
      manipulative actions, engaging motor, somatosensory and associative areas of the
      cortex while requiring only minimal forces and relatively simple movement
      patterns. Using transcranial magnetic stimulation (TMS), we investigated task
      related changes in motor evoked potential (MEP) amplitude associated with
      unimanual haptic sensing in two related experiments. In Experiment I, we
      contrasted changes in the excitability of the hemisphere controlling the task
      hand in young and old adults under two trial conditions, i.e. when participants
      either touched a fine grating (smooth trials) or touched a coarse grating to
      detect its groove orientation (grating trials). In Experiment II, the same
      contrast between tasks was performed but with TMS applied over the hemisphere
      controlling the resting hand, while also addressing hemispheric (right vs. left)
      and age differences. RESULTS: In Experiment I, a main effect of trial type on MEP
      amplitude was detected (p = 0.001), MEPs in the task hand being ~50% larger
      during grating than smooth trials. No interaction with age was detected. Similar
      results were found for Experiment II, trial type having a large effect on MEP
      amplitude in the resting hand (p < 0.001) owing to selective increase in MEP size
      (~2.6 times greater) for grating trials. No interactions with age or side (right
      vs. left) were detected. CONCLUSIONS: Collectively, these results indicate that
      adding a haptic component to a simple unilateral finger action can elicit robust
      corticomotor facilitation not only in the working hemisphere but also in the
      opposite hemisphere. The fact that this facilitation seems well preserved with
      age, when task difficulty is adjusted, has some potential clinical implications.

PMID- 22416787
TI  - Characterization of Leishmania infantum thiol-dependent reductase 1 and
      evaluation of its potential to induce immune protection.
AB  - The need to develop an effective vaccine against leishmaniasis to prevent the 2
      million new cases each year led to the search for antigens able to elicit
      protection against infection with Leishmania. In this study, we have
      characterized a parasite-specific protein of Leishmania infantum named thiol
      dependent reductase 1 (TDR1). The protein is present in both life cycle stages of
      L. infantum with a notable higher expression in the amastigote forms, suggesting
      a role in the interaction between the parasite and the mammalian host. Thiol
      dependent reductase 1 is localized in the cytosol, although we were able to
      detect the protein in the culture medium of both promastigotes and axenic
      amastigotes, and consequently, TDR1 is considered an excreted/secreted molecule
      of the parasite. Therefore, we have evaluated the potential of TDR1 recombinant
      protein to protect against experimental challenge with L. infantum parasites
      using a murine model. Despite a reduction in spleen parasite load in the chronic
      phase of disease, TDR1 administration was not effective in the protection of
      Balb/c mice against visceral leishmaniasis and thus TDR1 do not have a crucial
      role in the modulation of mammalian host immune response, as observed with its
      protein counterpart Tc52 of Trypanosoma cruzi.

PMID- 22416788
TI  - Lymph node count threshold for optimal pelvic lymph node staging in prostate
      cancer.
AB  - OBJECTIVES: To test the relationship between the extent of pelvic lymph node
      dissection at radical prostatectomy and the rate of lymph node metastases, and to
      identify the ideal number of lymph nodes that should be removed to achieve an
      optimal staging. METHODS: We assessed 20 789 prostate cancer patients treated
      with radical prostatectomy and pelvic lymph node dissection between 2004 and
      2006. Receiver operating characteristics analyses were used to define the
      probability of correctly staging lymph node metastases patients according to
      lymph node count. Univariable and multivariable regression analyses tested the
      relationship between lymph node count and lymph node metastases rate. RESULTS:
      The average lymph node count was 6.4 (median 5.0). Overall, the lymph node
      metastases rate was 2.5%; and it resulted to be 0.2, 1.5 and 6.7% in low,
      intermediate and high-risk tumors, respectively. The rate of lymph node
      metastases was 3.5 and 6.7% in patients with 10 and 20 lymph node count,
      respectively. Removing 20 lymph nodes yielded a 90% probability of correctly
      staging lymph node metastases, regardless of risk group. In multivariable
      analysis, lymph node count was an independent predictor of lymph node metastases
      stage (odds ratio: 1.07, P < 0.001). CONCLUSIONS: A direct relationship might
      exist between the extent of pelvic lymph node dissection and the lymph node
      metastases rate. An extended pelvic lymph node dissection with at least 20 lymph
      nodes would offer correct lymph node staging in 90% of cases, regardless of tumor
      characteristics. This cut-off might be considered adequate by most surgeons. Such
      a high lymph node yield necessitates an anatomically extended pelvic lymph node
      dissection.

PMID- 22416789
TI  - A lifestyle intervention to reduce Type 2 diabetes risk in Dutch primary care:
      2.5-year results of a randomized controlled trial.
AB  - AIMS: To determine the effectiveness of a 2.5-year lifestyle intervention for
      Type 2 diabetes prevention in Dutch general practice compared with usual care.
      METHODS: A randomized controlled trial of 925 individuals at high risk for Type 2
      diabetes (FINDRISC-score >= 13) in 14 general practices in the Netherlands.
      Intervention consisted of lifestyle counselling from the nurse practitioner and
      the general practitioner. Usual care consisted of oral and written information at
      the start of the study. Study groups were compared over 2.5 years regarding
      changes in clinical and lifestyle measures. RESULTS: Both groups showed modest
      changes in body weight, glucose concentrations, physical activity and dietary
      intake [weight: intervention group, -0.8 (5.1) kg, usual care group, -0.4 (4.7)
      kg, (P=0.69); fasting plasma glucose: intervention group, -0.17 (0.4) mmol/l,
      usual care group, -0.10 (0.5) mmol/l, (P=0.10)]. Differences between groups were
      significant only for total physical activity and fibre intake. In the
      intervention group, self-efficacy was significantly higher in individuals
      successful at losing weight compared with unsuccessful individuals. No
      significant differences in participant weight loss were found between general
      practitioners and nurse practitioners with different levels of motivation or self
      efficacy. CONCLUSIONS: Diabetes risk factors could significantly be reduced by
      lifestyle counselling in Dutch primary care. However, intervention effects above
      the effects attributable to usual care were modest. Higher participant self
      efficacy seemed to facilitate weight loss. Lack of motivation or self-efficacy of
      professionals did not negatively influence participant guidance.

PMID- 22416790
TI  - A cohort evaluation of the laryngeal mask airway-SupremeTM in children.
AB  - OBJECTIVES: To assess the clinical performance of the laryngeal mask airway
      Supreme in children. AIM: The purpose of this prospective audit was to evaluate
      the feasibility of the laryngeal mask airway-Supreme in clinical practice and
      generate data for future comparison trials. BACKGROUND: The laryngeal mask airway
      Supreme is a new second-generation supraglottic airway that was recently released
      in limited pediatric sizes (sizes 1, 2). METHODS: One hundred children, ASA I
      III, newborn to 16 years of age, and undergoing various procedures requiring a
      size 1, 2, or 3 laryngeal mask airway-Supreme were studied. Assessments included
      insertion success rates, airway leak pressures, success of gastric tube
      insertion, quality of airway, and perioperative complications. RESULTS: The first
      time insertion success rate was 97%, with an overall insertion success rate of
      100%. The mean initial airway leak pressure for all patients was 22.3 +/- 6.6 cm
      H(2) O. Gastric tube placement was possible in 98% of patients. Complications
      were noted in six patients: coughing or laryngospasm (n = 3), sore throat (n =
      1), and dysphonia (n = 2). CONCLUSIONS: The laryngeal mask airway-Supreme was
      inserted with a high degree of success on the first attempt by clinicians with
      limited prior experience with the device. It was effectively used for a variety
      of procedures in children undergoing spontaneous and mechanical ventilation with
      minimal complications. The leak pressures demonstrated in this study, along with
      access for gastric decompression, suggest that the laryngeal mask airway-Supreme
      may be an effective device for positive pressure ventilation in children.

PMID- 22416791
TI  - A cancer screening intervention for underserved Latina women by lay educators.
AB  - OBJECTIVES: Inadequate screening adherence for breast, cervical, and colorectal
      cancer among Latinas places them at greater risk for poor survival rates, once
      diagnosed. The purpose of this study was to examine two delivery methods of lay
      health educators (promotoras de salud) to increase screening behavior and
      evaluate costs. METHODS: This community-based group randomized trial assigned
      Latinas due for breast, cervical, or colorectal cancer screening (n=1006) to
      promotora-taught cancer screening/prevention classes delivered individually (IND)
      or in social support groups (SSG) over 8 weeks. Screening behaviors were assessed
      immediately after and 3 and 15 months after intervention. Intervention costs per
      study arm were compared. RESULTS: Screening and maintenance behaviors were not
      significantly different between SSG and IND for any one type of cancer screening,
      but with a study entry requirement that participants were either never screened
      or due for screening, postintervention screening rates (that is, completing a
      screening that was due) were notable (39.4% and 45.5%, respectively). The cost of
      achieving any one screening was much higher for IND participants. CONCLUSIONS:
      SSG vs. IND delivery did not significantly affect cancer screening behaviors, but
      both interventions produced robust achievement of screenings for previously
      nonadherent participants. Group-based promotora-led interventions supporting
      social involvement are recommended as a more cost-effective approach to achieving
      cancer screening among Latina women.

PMID- 22416792
TI  - Marital birth and early child outcomes: the moderating influence of marriage
      propensity.
AB  - Using data from the Fragile Families and Child Well-Being Study, the present
      study tested whether the benefits of a marital birth for early child development
      diminish as parents' risk of having a nonmarital birth increases (N = 2,285). It
      was hypothesized that a child's likelihood of being born to unmarried parents is
      partly a function of father characteristics that predict his capacity to promote
      child development. Results partially supported hypothesis. A positive association
      emerged between parental marriage and cognitive outcomes at age 3 only for
      children whose parents were likely to be married at the child's birth, suggesting
      average differences between children in married and unmarried families may
      overestimate the benefit of marriage in subpopulations most impacted by
      nonmarital birth.

PMID- 22416793
TI  - The needs of carers of men with prostate cancer and barriers and enablers to
      meeting them: a qualitative study in England.
AB  - The aim of this study was to explore the needs of carers of men with prostate
      cancer and to identify barriers and enablers to meeting these needs. Carers were
      recruited to focus groups or interviews. These were recorded, transcribed and
      analysed by two researchers using Nvivo QSR6 and the Framework approach to index,
      chart and analyse data to identify emergent themes of the needs of carers, and
      barriers and enablers to meeting these needs. Fifteen carers took part in focus
      groups and 19 were interviewed. Carers' needs varied and were often unmet because
      of barriers to existing services. Carers needed: information; emotional support;
      practical support; effective medical care for the patient. Barriers to carers
      meeting their needs included: lack of awareness of sources of help; lack of
      understanding of information; reluctance to ask for help; prioritising the
      patient's needs. Enablers included better signposting to information and sources
      of support, and assessment of their needs. Interventions to address these needs
      should be developed taking account of the barriers and enablers identified here,
      and the experience of reported interventions for carers of other cancer patients.
      Carers should be offered an assessment to establish their needs and directed to
      appropriate sources of help.

PMID- 22416794
TI  - Intraepidermal sebaceous carcinoma occurring concurrently with actinic keratosis.

PMID- 22416795
TI  - Depressive symptoms interfere with post-rehabilitation exercise: outcome
      expectancies and experience as mediators.
AB  - The aim of the study was to examine the relationship between depressive symptoms
      and physical exercise by unveiling how outcome expectancies regarding exercise
      and positive exercise experience could mediate between depressive symptoms and
      exercise. A longitudinal study included 178 cardiac and orthopedic rehabilitation
      patients in Germany. Patients responded to psychometric scales at two points in
      time with a six-week interval, assessing depressive symptoms (Time 1), outcome
      expectancies regarding exercise (Time 1), exercise experiences (Time 2), and
      exercise behavior (Times 1 and 2). Depressive symptoms were negatively related to
      physical exercise (r =- 0.18), to positive outcome expectancies (r =- 0.23), and
      to positive exercise experiences (r =- 0.26). In a multiple-step mediation model,
      expectancies and experiences mediated between depressive symptoms and exercise.
      In total, 15% of the exercise variance was accounted for. Outcome expectancies
      and a lack of positive experience seem to partly explain why depressed
      individuals are less likely to exercise.

PMID- 22416796
TI  - The FCGR2B rs10917661 polymorphism may confer susceptibility to ankylosing
      spondylitis in Han Chinese: a case-control study.
AB  - OBJECTIVE: Single-nucleotide polymorphisms (SNPs) in the Fc gamma receptor IIB
      (FCGR2B) gene have recently been found to be associated with several human
      autoimmune diseases. We undertook the current study to investigate the influence
      of these polymorphisms on the risk of ankylosing spondylitis (AS). METHOD: A
      total of 306 patients with AS from Anhui, China, fulfilling the modified New York
      Criteria, and 300 matched healthy controls were analysed. All subjects were
      genotyped for two SNPs (rs1050501, rs10917661) in the FCGR2B gene, and the
      SNaPshot Assay was used for genotyping. RESULTS: SNP rs10917661 was significantly
      associated with AS [C vs. T: odds ratio (OR) 1.723, 95% confidence interval (CI)
      1.086-2.733, p = 0.020; genotype: p = 0.026] whereas no association was found for
      rs1050501. Furthermore, no haplotype was found to be associated with AS.
      CONCLUSION: These findings indicated that rs10917661 may be a novel SNP involved
      in AS genetic predisposition in the Han Chinese population.

PMID- 22416797
TI  - Atom-economical synthesis of functionalized cycloalkanes via catalytic redox
      cycloisomerization of propargyl alcohols.
AB  - An atom-economical procedure for the direct synthesis of cycloalkanes from
      propargyl alcohols is reported. This high-yielding one-pot process involves a
      sequence consisting of a Ru-catalyzed redox isomerization of ynols into enones or
      an enal followed by an intramolecular Michael addition of a variety of carbon
      nucleophiles. Furthermore, an asymmetric variant of this protocol realized by the
      aid of a chiral nonracemic diamine catalyst, which provides the cyclization
      products in up to 97% ee, is presented.

PMID- 22416798
TI  - Body fat distribution in HIV-infected patients treated for 96 weeks with
      darunavir/ritonavir monotherapy versus darunavir/ritonavir plus nucleoside
      reverse transcriptase inhibitors: the MONOI-ANRS136 substudy.
AB  - OBJECTIVES: The aim of the study was to evaluate fat tissue distribution in HIV
      infected patients with suppressed viraemia treated with darunavir/ritonavir
      (darunavir/r) monotherapy versus darunavir/r triple therapy. METHODS: This study
      was a substudy of the randomized, multicentre, open-label MONOI-ANRS 136 trial.
      Body fat distribution and metabolic parameters were measured at baseline, week 48
      and week 96. RESULTS: In total, 156 patients of the 225 initially enrolled in the
      MONOI trial participated in this study, 75 in the darunavir/r monotherapy arm and
      81 in the darunavir/r triple-therapy arm. The median limb fat increase from
      baseline was +0.34 kg [interquartile range (IQR) -0.040 to +1.140 kg; P < 0.001]
      at week 48 and +0.33 kg (IQR -0.14 to +1.26 kg; P = 0.001) at week 96 in the
      monotherapy arm, while there was no change (-0.02 kg; IQR -0.53 to +0.52 kg) at
      week 48 and then an increase of +0.23 kg (IQR -0.45 to +0.87 kg; P = 0.046) at
      week 96 in the triple-therapy arm. The two arms differed significantly at week 48
      (P = 0.001) but not at week 96. The median increase in trunk fat was +0.73 kg
      (IQR -0.24 to +1.60 kg; P < 0.001) and 0.60 kg (IQR -0.41 to +1.49 kg; P = 0.03)
      at week 48 and +1.16 kg (IQR -0.17 to +2.75 kg; P < 0.001) and +0.90 kg (IQR 
      0.51 to +2.34 kg; P = 0.001) at week 96 in the monotherapy and triple-therapy
      arms, respectively, with no difference between arms. At week 96, the only
      biological change was a glucose level elevation in the monotherapy arm (median
      +4.0 mg/dL; IQR -4.0 to +7.0 mg/dL) compared with the triple-therapy arm (P =
      0.012). CONCLUSIONS: Overall, body fat tissue increased in patients on
      darunavir/r monotherapy and triple therapy, with no difference between the arms
      over 96 weeks. The only difference found was a delayed increase in limb fat
      tissue in the triple-therapy arm compared with the monotherapy arm in the first
      year.

PMID- 22416799
TI  - Green tea prevents obesity by increasing expression of insulin-like growth factor
      binding protein-1 in adipose tissue of high-fat diet-fed mice.
AB  - It is known that green tea has the ability to prevent obesity, but the underlying
      molecular mechanism is not fully understood to date. A preventive mechanism of
      green tea on obesity in C57BL/6 mice fed a high-fat (HF) diet was investigated by
      evaluating the expression levels of obesity-related proteins in mesenteric white
      adipose tissue by using protein array. An increase in the expression level of
      insulin-like growth factor binding protein (IGFBP)-1 by green tea was found in
      the white adipose tissues of both control and HF diet-fed mice by protein array
      and confirmed by Western blot. Moreover, the expression level was negatively
      correlated with adipose tissue weight. In 3T3-L1 adipocytes, treatment with green
      tea and its major polyphenol, (-)-epigallocatechin gallate, induced the
      expression of IGFBP-1 in a dose-dependent manner by Western blot. In conclusion,
      IGFBP-1 in adipose tissue is a novel molecule target for the prevention of
      obesity by green tea.

PMID- 22416800
TI  - Evaluation of destructive effects of exposure to cisplatin during developmental
      stage: no profound evidence for sex differences in impaired motor and memory
      performance.
AB  - We have elucidated the alteration in hippocampal and cerebellum function
      following chronic cisplatin treatment in male and female rats. Hippocampus and
      cerebellum related behavioral dysfunction in cisplatin-treated
      [intraperitoneally, 5 mg/(kg/week) for 5 weeks from 23-day-old] rats were
      analyzed using explorative, motor function, learning, and memory tasks (grasping,
      rotarod, open field, and Morris water maze tests). Exposure to cisplatin impaired
      the motor coordination in male and female rats. Exposure to cisplatin was
      reflected by a decrease in grasping time compared to vehicle-treated controls
      (saline) only in male rat while there were not any differences in female rats.
      When the rearing frequency, total distance moved and velocity of their recorded
      in open fieldtest, both males and females were dramatically affected by exposure
      to cisplatin. Compared to the saline, male and female rats trained 5 weeks after
      cisplatin injection showed significant memory deficits in the Morris water maze
      test. However, hippocampal and cerebellum functions of male and female rats were
      profoundly affected by exposure to cisplatin while no sex differences in the most
      variable were evident.

PMID- 22416801
TI  - Gonadotropin-releasing hormone: an update review of the antagonists versus
      agonists.
AB  - Gonadotropin-releasing hormone agonists and antagonists provide androgen
      deprivation therapy for prostate cancer. Unlike agonists, gonadotropin-releasing
      hormone antagonists have a direct mode of action to block pituitary gonadotropin
      releasing hormone receptors. There are two licensed gonadotropin-releasing
      hormone antagonists, degarelix and abarelix. Of these, degarelix is the more
      extensively studied and has been documented to be more effective than the well
      established, first-line agonist, leuprolide, in terms of substantially faster
      onset of castration, faster suppression of prostate-specific antigen, no risk for
      testosterone surge or clinical flare, and improved prostate-specific antigen
      progression-free survival, suggesting a delay in castration resistance. Other
      than minor injection-site reactions, degarelix is generally well tolerated,
      without systemic allergic reactions and with most adverse events consistent with
      androgen suppression or the underlying condition. In conclusion, degarelix
      provides a rational, first-line androgen-deprivation therapy suitable for the
      treatment of prostate cancer, with faster onset of castration than with agonists,
      and no testosterone surge. Furthermore, data suggest that degarelix improves
      disease control compared with leuprolide, and might delay the onset of castration
      resistant disease. In view of these clinical benefits and the lack of need for
      concomitant anti-androgen treatment, gonadotropin-releasing hormone antagonists
      might replace gonadotropin-releasing hormone agonists as first-line androgen
      deprivation therapy in the future.

PMID- 22416802
TI  - Vibrotactile difference thresholds: effects of vibration frequency, vibration
      magnitude, contact area, and body location.
AB  - It has not been established whether the smallest perceptible change in the
      intensity of vibrotactile stimuli depends on the somatosensory channel mediating
      the sensation. This study investigated intensity difference thresholds for
      vibration using contact conditions (different frequencies, magnitudes, contact
      areas, body locations) selected so that perception would be mediated by more than
      one psychophysical channel. It was hypothesized that difference thresholds
      mediated by the non-Pacinian I (NPI) channel and the Pacinian (P) channel would
      differ. Using two different contactors (1-mm diameter contactor with 1-mm gap to
      a fixed surround; 10-mm diameter contactor with 2-mm gap to the surround)
      vibration was applied to the thenar eminence and the volar forearm at two
      frequencies (10 and 125 Hz). The up-down-transformed-response method with a three
      down-one-up rule provided absolute thresholds and also difference thresholds at
      various levels above the absolute thresholds of 12 subjects (i.e., sensation
      levels, SLs) selected to activate preferentially either single channels or
      multiple channels. Median difference thresholds varied from 0.20 (thenar eminence
      with 125-Hz vibration at 10 dB SL) to 0.58 (thenar eminence with 10-Hz vibration
      at 20 dB SL). Median difference thresholds tended to be lower for the P channel
      than the NPI channel. The NPII channel may have reduced difference thresholds
      with the smaller contactor at 125 Hz. It is concluded that there are large and
      systematic variations in difference thresholds associated with the frequency, the
      magnitude, the area of contact, and the location of contact with vibrotactile
      stimuli that cannot be explained without increased understanding of the
      perception of supra-threshold vibrotactile stimuli.

PMID- 22416803
TI  - Treatment with captopril abrogates the altered expression of alpha1 macroglobulin
      and alpha1 antiproteinase in sera of spontaneously hypertensive rats.
AB  - BACKGROUND: Proteins that are associated with hypertension may be identified by
      comparing the 2-dimensional gel electrophoresis (2-DE) profiles of the sera of
      spontaneously hypertensive rats (SHR) with those generated from normotensive
      Spraque-Dawley rats (SDR). RESULTS: Five proteins of high abundance were found to
      be significantly altered when the 2-DE serum profiles of the SHR were compared to
      those that were similarly generated from the SDR. Analysis by mass spectrometry
      and database search identified the proteins as retinol binding protein 4,
      complement C3, albumin (19.9 kDa fragment), alpha1 macroglobulin and alpha1
      antiproteinase, which are all known to be associated with hypertension. The
      altered expression of the two latter proteins was found to be abrogated when
      similar analysis was performed on sera of the SHR that were treated with
      captopril. CONCLUSION: Our data suggests that serum alpha1 macroglobulin and
      alpha1 antiproteinase are potentially useful complementary biomolecular
      indicators for monitoring of hypertension.

PMID- 22416804
TI  - Evaluation of a DVD for women with diabetes: impact on knowledge and attitudes to
      preconception care.
AB  - AIMS: To determine if an educational DVD increases knowledge and changes
      attitudes of women with diabetes towards preconception care. METHODS: Ninety
      seven women with diabetes (Type 1, n = 89; Type 2, n = 8), aged 18-40 years,
      completed a pre-DVD and post-DVD intervention study by postal questionnaire.
      Beliefs and attitudes associated with preventing an unplanned pregnancy and
      seeking preconception care were assessed using a validated questionnaire; scales
      included benefits, barriers, personal attitudes and self-efficacy. Knowledge of
      pregnancy planning and pregnancy-related risks were assessed by a 22-item
      questionnaire. RESULTS: After viewing the DVD there was significant positive
      change in women's perceived benefits of, and their personal attitudes to,
      receiving preconception care and using contraception: change in score post-DVD
      viewing 0.7 (95% confidence interval 0.3, 1.2), P = 0.003, and 0.8 (0.3, 1.2), P
      = 0.001, respectively. The DVD significantly improved self-efficacy, that is,
      self-confidence to use contraception for prevention of an unplanned pregnancy and
      to access preconception care [3.3 (1.9, 4.7), P < 0.001], and significantly
      reduced perceived barriers to preconception care [-0.7 (-1.2, -0.2), P = 0.01].
      Knowledge of pregnancy planning and pregnancy-related risks increased
      significantly after viewing the DVD: mean increase was 37.6 +/- 20.0%, P < 0.001,
      and 16.9 +/- 21.2%, P < 0.001, respectively. CONCLUSIONS: This study demonstrates
      the effectiveness of a DVD in increasing knowledge and enhancing attitudes of
      women with diabetes to preconception care. This DVD could be used as a
      prepregnancy counselling resource to prepare women with diabetes for pregnancy.

PMID- 22416805
TI  - Recognition bias and the physical attractiveness stereotype.
AB  - Previous studies have found a recognition bias for information consistent with
      the physical attractiveness stereotype (PAS), in which participants believe that
      they remember that attractive individuals have positive qualities and that
      unattractive individuals have negative qualities, regardless of what information
      actually occurred. The purpose of this research was to examine whether
      recognition bias for PAS congruent information is replicable and invariant across
      a variety of conditions (i.e. generalizable). The effects of nine different
      moderator variables were examined in two experiments. With a few exceptions, the
      effect of PAS congruence on recognition bias was independent of the moderator
      variables. The results suggest that the tendency to believe that one remembers
      information consistent with the physical attractiveness stereotype is a robust
      phenomenon.

PMID- 22416806
TI  - Age related prevalence of severe left ventricular hypertrophy in essential
      hypertension: echocardiographic findings from the ETODH study.
AB  - AIM: We sought to investigate the prevalence and correlates of severe left
      ventricular hypertrophy (LVH) in relation to age in a large cohort of essential
      hypertensives referred to a single outpatient hypertension clinic. METHODS: A
      total of 3752 (mean age 53+/-13 years, 53% men) untreated (29.5%) and treated
      hypertensive patients categorized in three age groups (I: 18-40 years; II: 41-64
      years; III: >=65 years) were considered for this analysis. All patients underwent
      extensive investigations searching for target organ damage. LVH, defined as LV
      mass >=49/45 g/m(2.7) in men/women, respectively, was graded as mild, moderate
      and severe according to Lang's report. RESULTS: LVH prevalence was 29.4% in group
      I, 48.2% in group II and 63.6% in group III. Overall, more than one fourth of
      patients with LVH had a severely increased LV mass index; the likelihood of
      having severe LVH was two- and four-fold higher in elderly hypertensives than in
      their middle-aged and young counterparts, respectively. Increasing age and LVH
      degree were both associated with a greater prevalence of concentric LV geometry
      as well as of extra-cardiac organ damage (i.e. carotid intima-media thickness).
      CONCLUSIONS: LVH is a highly prevalent organ damage in essential hypertensives,
      particularly in the elderly, who exhibited a more severe increase of LV mass
      index, higher relative wall thickness and extra-cardiac organ damage compared
      with young and middle-aged sub-groups. Our findings suggest that the assessment
      of cardiovascular risk by grading LVH rather than simply defining the
      presence/absence of this cardiac phenotype could improve therapeutic strategies
      in the hypertensive population, particularly in the elderly.

PMID- 22416808
TI  - The use of pneumoperitoneum during laparoscopic surgery as a model to study
      pathophysiologic phenomena: the correlation of cardiac functionality with
      computerized acoustic indices--preliminary data.
AB  - BACKGROUND: Induction of pneumoperitoneum during laparoscopic surgery leads to
      diverse cardiovascular changes that can be used as a model to study
      pathophysiologic phenomena. Application of novel signal processing and figure
      extraction enabled searching for correlation between various signals and
      pathophysiologic setting. Our aim was to quantitatively correlate cardiac
      functionality (as expressed by cardiac output) with the spectral energy of the
      first heart sound (S1) obtained from the phonocardiogram, during laparoscopic
      surgery. PATIENTS AND METHODS: Patients who were scheduled for elective
      laparoscopic operations were enrolled in the study. Cardiac output was maximally
      changed during anesthesia and abdominal insufflation and was obtained from the
      arterial pressure wave (FloTracTM sensor and VigileoTM monitor [Edwards
      Lifesciences Ltd.]). Heart signals were recorded during surgery from each subject
      by a computerized digital data acquisition system. The automatic analysis of the
      heart sounds included segmentation that was based on the energy envelope of the
      heart sounds together with analysis of the electrocardiogram signal. We analyzed
      the morphology of the sounds using hierarchial cluster analysis to remove those
      sounds that were not reliably recorded. The magnitude of the amplitude of heart
      sounds was obtained by using the Hilbert transform for each heartbeat.
      Statistical analysis was based on linear regression. RESULTS: Following exclusion
      of 3 patients (mainly because of technical reasons), we were left with 7 patients
      who demonstrated statistically significant positive correlation between cardiac
      index and the amplitude of S1 (regression coefficient between 0.4 and 0.9,
      P<.05). Linear regression analysis was done on the normalized values of all 7
      patients and was found to be highly significant. CONCLUSIONS: In this study we
      have demonstrated significant linear correlation between the acoustic amplitude
      (spectral energy) of S1 and cardiac functionality, through sophisticated
      computerized analysis, using the pneumoperitoneum model for changing the cardiac
      output.

PMID- 22416807
TI  - Transcriptional profile analysis of E3 ligase and hormone-related genes expressed
      during wheat grain development.
AB  - BACKGROUND: Wheat grains are an important source of food, stock feed and raw
      materials for industry, but current production levels cannot meet world needs.
      Elucidation of the molecular mechanisms underlying wheat grain development will
      contribute valuable information to improving wheat cultivation. One of the most
      important mechanisms implicated in plant developmental processes is the ubiquitin
      proteasome system (UPS). Among the different roles of the UPS, it is clear that
      it is essential to hormone signaling. In particular, E3 ubiquitin ligases of the
      UPS have been shown to play critical roles in hormone perception and signal
      transduction. RESULTS: A NimbleGen microarray containing 39,179 UniGenes was used
      to study the kinetics of gene expression during wheat grain development from the
      early stages of cell division to the mid-grain filling stage. By comparing 11
      consecutive time-points, 9284 differentially expressed genes were identified and
      annotated during this study. A comparison of the temporal profiles of these genes
      revealed dynamic transcript accumulation profiles with major reprogramming events
      that occurred during the time intervals of 80-120 and 220-240 degrees Cdays. The
      list of the genes expressed differentially during these transitions were
      identified and annotated. Emphasis was placed on E3 ligase and hormone-related
      genes. In total, 173 E3 ligase coding genes and 126 hormone-related genes were
      differentially expressed during the cell division and grain filling stages, with
      each family displaying a different expression profile. CONCLUSIONS: The
      differential expression of genes involved in the UPS and plant hormone pathways
      suggests that phytohormones and UPS crosstalk might play a critical role in the
      wheat grain developmental process. Some E3 ligase and hormone-related genes seem
      to be up- or down-regulated during the early and late stages of the grain
      development.

PMID- 22416809
TI  - Tunable plasmon coupling in distance-controlled gold nanoparticles.
AB  - Plasmons are resonant excitations in metallic films and nanoparticles. For small
      enough static distances of metal nanoparticles, additional plasmon-coupled modes
      appear as a collective excitation between the nanoparticles. Here we show, by
      combining poly(N-isopropylacrylamide) micro- and nanospheres and Au
      nanoparticles, how to design a system that allows controllably and reversibly
      switching on and off, and tuning the plasmon-coupled mode.

PMID- 22416810
TI  - Being a male nurse in Portugal during Salazar's dictatorship (1940-70).
AB  - In several western countries, nursing was clearly seen as an occupation for
      women. With the creation of the first nursing schools, the gendering of the
      profession was accelerated. Male nurses' contribution to the development of the
      profession was limited in comparison with women's. However, the situation was
      slightly different in Portugal. This article aims at demonstrating a specific
      example of the gendering of the nursing profession, by simply copying the western
      model--considered the most developed--without questioning the consequences or
      even whether it was adapted to the country that had a different nursing
      tradition. Because the consequences of this gendering are still felt nowadays,
      this article opens a reflection on how complex it is to follow a foreign nursing
      model and on the issues associated with such a copy. Qualitative and quantitative
      analysis of several historical documents and interviews with several retired
      nurses contributed to an understanding of how men became nurses and how they
      worked in Portugal, despite gender discrimination, between 1940 and 1970. With
      different nursing training and job opportunities, Portuguese male nurses still
      managed to contribute, even beyond that of female nurses, to the improvement of
      the nursing profession.

PMID- 22416812
TI  - Life satisfaction and health related quality of life among low-income medical
      patients: the mediating influence of self-esteem.
AB  - This study investigated the relationship between life satisfaction, self-esteem,
      and perceived health for an ethnically diverse, low SES sample of primary care
      patients. Results indicated that several specific domains of health-related
      quality of life (HRQL), including health perception, social functioning, mental
      health, and energy/fatigue, significantly predicted life satisfaction in this
      sample of 60 patients. Self-esteem mediated this relationship, partially with
      health perception and fully with the remaining three domains. The results of this
      study underscore the importance of healthcare interventions that consider the
      bidirectional relationship between physical and emotional well-being.

PMID- 22416811
TI  - Pantothenate kinase-associated neurodegeneration is not a synucleinopathy.
AB  - AIMS: Mutations in the pantothenate kinase 2 gene (PANK2) are responsible for the
      most common type of neurodegeneration with brain iron accumulation (NBIA), known
      as pantothenate kinase-associated neurodegeneration (PKAN). Historically, NBIA is
      considered a synucleinopathy with numerous reports of NBIA cases with Lewy bodies
      and Lewy neurites and some cases reporting additional abnormal tau accumulation.
      However, clinicopathological correlations in genetically proven PKAN cases are
      rare. We describe the clinical, genetic and neuropathological features of three
      unrelated PKAN cases. METHODS: All three cases were genetically screened for the
      PANK2 gene mutations using standard Sanger polymerase chain reaction sequencing.
      A detailed neuropathological assessment of the three cases was performed using
      histochemical and immunohistochemical preparations. RESULTS: All cases had
      classical axonal swellings and Perls' positive iron deposition in the basal
      ganglia. In contrast to neuroaxonal dystrophies due to mutation of the
      phospholipase A2, group VI (PLA2G6) gene, in which Lewy body pathology is
      widespread, no alpha-synuclein accumulation was detected in any of our PKAN
      cases. In one case (20-year-old male) there was significant tau pathology
      comprising neurofibrillary tangles and neuropil threads, with very subtle tau
      pathology in another case. CONCLUSIONS: These findings indicate that PKAN is not
      a synucleinopathy and, hence the cellular pathways implicated in this disease are
      unlikely to be relevant for the pathomechanism of Lewy body disorders.

PMID- 22416814
TI  - Evaluation of the composition of vine shoots and oak chips for oenological
      purposes by superheated liquid extraction and high-resolution liquid
      chromatography-time-of-flight/mass spectrometry analysis.
AB  - Vine shoots are characterized in this research and compared to oak chips,
      frequently employed in the aging of wine or spirits. For this purpose, liquid
      chromatography-diode array detection and liquid chromatography-time-of
      flight/mass spectrometry (LC-TOF/MS) analyses of hydroalcoholic extracts from
      vine shoots pertaining to 18 different vine varieties and from five varieties of
      oak chips have been carried out. The concentrations of a representative panel of
      interesting compounds from an oenological point of view have been compared in the
      extracts, finding similarity patterns for many of them. The analysis by LC-TOF/MS
      in high accuracy mode has led to the identification of numerous compounds in the
      hydroalcoholic extracts. The statistical analysis has enabled identification of
      the vine-shoot varieties providing extracts with more similar composition to that
      given by extracts from oak chips. Therefore, these vine-shoots varieties are
      suitable to be presented as an alternative to the use of oak barrels or oak chips
      in the aging process of wine and spirits.

PMID- 22416815
TI  - Direct heteroarylation of tautomerizable heterocycles into unsymmetrical and
      symmetrical biheterocycles via Pd/Cu-catalyzed phosphonium coupling.
AB  - The direct cross-coupling of tautomerizable heterocycles with various
      unfunctionalized heteroarenes has been achieved through PyBroP-mediated and Pd/Cu
      catalyzed sequential C-OH/C-H activation. The methodology allows a facile entry
      into novel diazine-azole biheterocyclic frameworks. Moreover, an unprecedented Pd
      catalyzed phosphonium homocoupling of tautomerizable heterocycles was also
      developed to afford a direct synthetic route to symmetrical 1,2-, 1,3-, and 1,4
      bidiazine units.

PMID- 22416813
TI  - Elevated alanine aminotransferase in antiretroviral-naive HIV-infected African
      patients: magnitude and risk factors.
AB  - BACKGROUND: Alanine aminotransferase (ALT) is commonly used to measure liver
      injury in resource-limited settings. Elevations in ALT are predictive of
      increased mortality from liver disease and may influence the choice of first-line
      antiretroviral therapy (ART). METHODS: A cross-sectional analysis of the
      prevalence and predictors of elevated ALT (defined as >40 IU/L) was conducted.
      ART-naive, HIV-infected adults with a baseline ALT measurement who were enrolled
      in any of the 18 HIV Care and Treatment Clinics in Dar es Salaam, Tanzania
      between November 2004 and December 2009 were included in the study. Median values
      were calculated and log-binomial regression models were used to examine
      predictors of elevated ALT. RESULTS: During the study period, 41891 adults had a
      baseline ALT measurement performed. The prevalence of ALT >40, >120 and >200 IU/L
      was 13, 1 and 0.3%, respectively. In multivariate analyses, male sex, CD4 T
      lymphocyte count <200 cells/MUL and higher World Health Organization (WHO)
      clinical stages were associated with a significantly higher risk of ALT >40 IU/L
      (all P<0.01). Hypertryglyceridaemia, hyperglycaemia and hepatitis B virus (HBV)
      coinfection (positive for HBV surface antigen) were significantly associated with
      a higher risk of elevated ALT. Pregnancy, anaemia, low-density lipoprotein
      cholesterol >130 mg/dL and current tuberculosis treatment were associated with a
      significantly reduced risk for elevated ALT. CONCLUSIONS: In this HIV-infected,
      ART-naive Tanzanian population, extreme elevations in ALT were infrequent but
      minor elevations were not uncommon. Antiretrovirals with potentially hepatotoxic
      side effects should be initiated with caution in male patients, and in patients
      with HBV coinfection, advanced immunosuppression and components of the metabolic
      syndrome.

PMID- 22416816
TI  - Self-reported differences on measures of executive function in a patient sample
      of pathological gamblers.
AB  - Patients seeking help for pathological gambling often exhibit features of
      impulsivity, cognitive rigidity, poor judgment, deficits in emotion regulation,
      and excessive preoccupation with gambling. Some of these characteristics are also
      common among patients presenting with neurological pathology associated with
      executive deficits. Evidence of executive deficits have been confirmed in
      pathological gamblers using objective neurocognitive tests, however, it remains
      to be seen if such findings will emerge in self-report measures of executive
      control. These observations led to the current investigation of differences
      between a group of pathological gamblers (n = 62) and a comparison group (n = 64)
      using the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF
      A). Significant differences between the groups emerged over all nine subscales of
      executive functioning with the most dramatic differences on BRIEF-A subscales
      Inhibit, Plan/Organize, Shift, Emotion Control, Self-Monitor, and Initiate among
      the pathological gamblers. These results provide evidence that support findings
      among pathological gamblers using objective neuropsychological measures and
      suggest that the BRIEF-A may be an appropriate instrument to assess possible
      problems with executive control in this population.

PMID- 22416817
TI  - Effect of non-lattice oxygen on ZrO2-based resistive switching memory.
AB  - ZrO2-based resistive switching memory has attracted much attention according to
      its possible application in the next-generation nonvolatile memory. The
      Al/ZrO2/Pt resistive switching memory with bipolar resistive switching behavior
      is revealed in this work. The thickness of the ZrO2 film is only 20 nm. The
      device yield improved by the non-lattice oxygen existing in the ZrO2 film
      deposited at room temperature is firstly proposed. The stable resistive switching
      behavior and the long retention time with a large current ratio are also
      observed. Furthermore, it is demonstrated that the resistive switching mechanism
      agrees with the formation and rupture of a conductive filament in the ZrO2 film.
      In addition, the Al/ZrO2/Pt resistive switching memory is also possible for
      application in flexible electronic equipment because it can be fully fabricated
      at room temperature.

PMID- 22416818
TI  - Adalimumab therapy for psoriasis in real-world practice: efficacy, safety and
      results in biologic-naive vs. non-naive patients.
AB  - BACKGROUND: Patients and the course of treatment in daily practice are different
      from randomized controlled trials (RCTs). OBJECTIVES:  PRIMARY OBJECTIVE: to
      analyse the percentage of patients achieving PASI 75. SECONDARY OBJECTIVES: PASI
      50, PASI 90, PASI 100 responses, the percentage of patients experiencing at least
      one serious adverse event (SAE) and the response in biologic-naive vs. non-naive
      patients. METHODS: Prospectively collected efficacy and safety data of a cohort
      of psoriasis patients treated with adalimumab in daily practice between May 2007
      and July 2011 were analyzed. Efficacy was determined using an intention-to-treat
      analysis and an as treated analysis, in comparison with the course baseline PASI
      before the start of adalimumab and the original baseline PASI before the start of
      any biologic therapy. RESULTS: Eighty-five patients received adalimumab therapy
      with a mean treatment duration of 1.4 (range 0.02-3.1) years. Compared with the
      original baseline PASI, PASI 75 response rates at week 12 and 24 were 34% and 38%
      (ITT). PASI 75 responses were well maintained until week 132. Only the PASI 75
      response rate at week 12 differed significantly between biologic-naive (56%) and
      non-naive patients (29%). Sixteen patients (19%) experienced 28 SAEs. Seven
      patients (8%) experienced SAEs considered possibly or probably related to
      adalimumab. CONCLUSIONS: In this cohort, PASI75 responses were substantial but
      lower than in RCTs and other daily practice studies. Efficacy was well maintained
      during more than 2 years of follow-up and differed only between biologic-naive
      and non-naive patients at week 12. The incidence of SAEs was low but seems higher
      than observed in RCTs.

PMID- 22416819
TI  - Executive function tests in early-onset psychosis: which one to choose?
AB  - People with schizophrenia exhibit executive functioning deficits, an area well
      investigated in the adult onset schizophrenia (AOS) group, but far less so in
      early-onset schizophrenia (EOS). Since EOS in general seems to exhibit poorer
      cognitive functions and is clinically more compromised than AOS, choice of
      efficient and sensitive assessment measures is not necessarily the same within
      the two groups. The MATRICS Consensus Cognitive Battery was developed for adults
      when studying treatment effects and uses Mazes (Neuropsychological Assessment
      Battery [NAB]) to assess executive functioning. We tested 31 adolescents with
      schizophrenia spectrum disorders and 66 healthy controls in order to examine how
      Mazes compares to two other commonly used tests to measure executive functioning,
      D-KEFS Color Word Interference Test (Stroop) and the Wisconsin Card Sorting Test
      (WCST). Significant discriminating power was found for all three measures.
      Patients performed 0.8-1.5 SD below controls with Stroop as the most sensitive
      measure, followed by Mazes and WCST. Mazes was selected by the MATRICS to assess
      treatment effects in AOS and is shown to be able. We find the instrument also
      able to separate adolescent patients from controls and thus, it appears a
      sensible choice in clinical settings. If a more elaborated neuropsychological
      evaluation of the executive functioning domain is needed, Stroop should be
      considered a complementary test.

PMID- 22416821
TI  - Urinary markers of renal inflammation in adolescents with Type 1 diabetes
      mellitus and normoalbuminuria.
AB  - AIMS: Patients with the highest albumin:creatinine ratio within the normal range
      are at an increased risk for developing microalbuminuria. The mechanistic basis
      for this is unknown, but may be related to renal inflammation. Our goal was to
      characterize the urinary excretion of cytokines/chemokines in normoalbuminuric
      adolescents with Type 1 diabetes to determine whether higher range
      normoalbuminuria is associated with evidence of renal inflammation. METHODS:
      Forty-two urinary cytokines/chemokines were measured in subjects who were
      screened for the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial.
      Urinary cytokines/chemokines were compared across low (n = 50), middle (n = 50)
      or high (n = 50) albumin:creatinine ratio tertile groups. RESULTS: At baseline,
      participants in the upper tertile were younger and had shorter diabetes duration
      compared with the other groups. Other clinical characteristics were similar.
      Urinary levels of interleukin 6, interleukin 8, platelet-derived growth factor-AA
      and RANTES differed across albumin:creatinine ratio tertiles, with higher values
      in patients in the middle and high tertiles compared with the lower tertile
      (ANCOVA P <= 0.01). CONCLUSIONS: Within the normal albumin:creatinine ratio
      range, higher urinary albumin excretion is associated with elevated urinary
      levels of inflammatory markers. Ultimately, this may provide mechanistic insights
      into disease pathophysiology and stratify the risk of nephropathy in Type 1
      diabetes.

PMID- 22416822
TI  - Integration of drugs and non-pharmacological intervention to Alzheimer patients.

PMID- 22416823
TI  - Evaluation of dementia-prevention classes for community-dwelling older adults
      with mild cognitive impairment.
AB  - AIM: The number of elderly people with dementia in Japan is likely to increase as
      the population ages. In some areas in Tottori Prefecture, dementia-prevention
      classes have been conducted for several years. In the present study, we evaluated
      dementia-prevention classes in nine districts of Tottori Prefecture in terms of
      cognitive function, assessment by the leader and subjective evaluation by
      participants. METHODS: The study's subjects included 112 community-dwelling
      elderly residents who were selected after a two-step screening. Data were
      collected according to the following four factors: (i) evaluation of cognitive
      function at the beginning and end of classes; (ii) the content of the classes;
      (iii) observations regarding the state of subjects; and (iv) participants'
      subjective evaluation obtained via a questionnaire distributed at the final
      class. RESULTS: In terms of cognitive function among all subjects, scores
      significantly improved after the dementia-prevention classes. However, there were
      no significant cognitive improvements in the districts where programmes were
      biased towards a single category (e.g. systemic exercise, creative activities).
      Based on class leaders' assessments, subjects showed improved appearance and
      facial expression in later classes. Participants became more involved in the
      programmes, and their interests in others increased. In terms of their daily
      lives, subjects became more involved with others and more active after
      participating in the classes. CONCLUSIONS: Dementia-prevention classes improved
      not only cognitive function but also other aspects of daily life, as well. We
      thought it was important to evaluate both objective and subjective factors
      related to the classes.

PMID- 22416820
TI  - Ccr4-Not complex: the control freak of eukaryotic cells.
AB  - The purpose of this review is to provide an analysis of the latest developments
      on the functions of the carbon catabolite-repression 4-Not (Ccr4-Not) complex in
      regulating eukaryotic gene expression. Ccr4-Not is a nine-subunit protein complex
      that is conserved in sequence and function throughout the eukaryotic kingdom.
      Although Ccr4-Not has been studied since the 1980s, our understanding of what it
      does is constantly evolving. Once thought to solely regulate transcription, it is
      now clear that it has much broader roles in gene regulation, such as in mRNA
      decay and quality control, RNA export, translational repression and protein
      ubiquitylation. The mechanism of actions for each of its functions is still being
      debated. Some of the difficulty in drawing a clear picture is that it has been
      implicated in so many processes that regulate mRNAs and proteins in both the
      cytoplasm and the nucleus. We will describe what is known about the Ccr4-Not
      complex in yeast and other eukaryotes in an effort to synthesize a unified model
      for how this complex coordinates multiple steps in gene regulation and provide
      insights into what questions will be most exciting to answer in the future.

PMID- 22416824
TI  - Prevalence of major depressive disorders and suicide in long-term care
      facilities: a report from northern Thailand.
AB  - BACKGROUND: Depression is a common mental illness among elderly Thais, but little
      is known about the occurrence of major depressive disorders (MDD) in long-term
      care (LTC) facilities. This study investigated the prevalence of MDD and suicide
      risk among residents in an LTC facility in northern Thailand. METHODS: For this
      cross-sectional study, a care team conducted a screening program for MDD and
      suicide risk among LTC residents in 2011. The screening process used the Mini
      International Neuropsychiatric Interview, the Geriatric Depression Scale-15, the
      patient and caregiver versions of the Cornell Scale for Depression in Dementia,
      the Core Symptom Index and the Mini Mental State Examination. RESULTS: In total,
      81 (of 113) residents participated in the study. The mean age was 76.96 +/- 7.17
      years old (range, 63-94), and 55.6% of participants were women. With the Mini
      Mental State Examination, 40.7% were found to have cognitive impairment, and with
      the Mini International Neuropsychiatric Interview, 23.5% met the criteria for
      current major depressive episodes. Though the majority was in the low-risk group,
      26 residents (32.1%) were reported as being at risk of suicide. The patient and
      caregiver versions of the Cornell Scale for Depression in Dementia, the Geriatric
      Depression Scale-15 and the Core Symptom Index proved useful for predicting major
      depressive episodes among the residents (P < 0.001, P = 0.004, P = 0.001 and P <
      0.001, respectively), including those with cognitive impairment (P = 0.006, P =
      0.020, P = 0.049 and P = 0.012, respectively). CONCLUSIONS: Nearly one-quarter of
      LTC facility residents were found to suffer from MDD, and a suicide risk was
      reported for one-third, though most of the cases were in the low-risk category.
      Further studies with a larger sample size are recommended to make these findings
      more precise and universally applicable.

PMID- 22416825
TI  - Comparing dementia patients' nighttime objective movement indicators with staff
      observations.
AB  - BACKGROUND: Pharmacological and non-pharmacological approaches are commonly used
      to treat patients' institutionalised for nighttime wandering. Actigraphy and
      other scales have been used to evaluate the efficacy of these treatments.
      However, in clinical settings, nursing records are often the sole source of daily
      observation of nighttime wandering. Thus, physicians rely on nursing records to
      evaluate pharmacological and non-pharmacological treatments. This study examined
      nighttime movements of patients with dementia, comparing the results of
      integrated circuit tag monitoring with hourly nighttime nursing records. We
      tested which factors were associated with agreement rates between the two data
      sources. METHODS: The study hospital was a general hospital in Osaka, Japan.
      Monitoring was conducted in a closed 60-bed dementia care unit. An integrated
      circuit tag monitoring system was used to monitor the movement of
      institutionalised dementia patients for over half a year. The distance moved per
      hour by subjects was measured using the monitoring system, and the data were
      compared with hourly nighttime nursing records. Agreement rates were calculated
      between the two data sources. RESULTS: Thirty-five patients were monitored.
      Between 10-30% of subjects moved at any given hour during the night. The overall
      agreement rate between sources of movement data was 39%. Agreement rates were
      significantly correlated with the interquartile of the distance moved, changes in
      medication, physical conditions, and behavioural and psychological symptoms of
      dementia measured during the day. CONCLUSIONS: Although the agreement rate was
      low, staff appeared to pay more attention to patients associated with notable
      events during the day and patients exhibiting variability in distance moved.

PMID- 22416826
TI  - Impaired memory and executive function associated with decreased medial temporal
      and prefrontal blood flow in Clinical Dementia Rating 0.5 status: the Osaki
      Tajiri project.
AB  - AIM: The Clinical Dementia Rating (CDR) is an assessment of dementia severity
      based on observations of activities of daily living, and a CDR of 0.5 (CDR 0.5)
      represents questionable dementia. A combination of the Cognitive Abilities
      Screening Instrument (CASI) and the Trail Making Test (TMT) scores discriminated
      CDR 0.5 subjects from healthy participants with a high degree of accuracy. We
      investigated the neurological background of CDR 0.5 subjects by correlating CASI
      and TMT scores with regional cerebral blood flow (rCBF) as measured by single
      photon emission computed tomography (SPECT). METHODS: From a community-based
      cohort, 22 CDR 0.5 participants were recruited. CASI and TMT scores, rCBF measure
      using [(123) I]-N-isopropyl-p-iodoamphetamine and SPECT were obtained. We
      evaluated the relationships between the CASI domain scores, between TMT scores
      and rCBF in a regions-of-interest-based analysis, and voxel-based analysis using
      Statistical Parametric Mapping 5 software. RESULTS: We found that lower rCBF in
      the left medial temporal cortex correlated with a decreased CASI domain recent
      memory score both in the regions-of-interest and statistical parametric mapping
      analysis. In both the regions-of-interest and statistical parametric mapping
      analysis, the rCBF in the left prefrontal cortex correlated with CASI domain
      remote memory and mental manipulation and concentration. CONCLUSIONS: Our results
      indicate that some CDR 0.5 subjects have functional impairments in the medial
      temporal lobe as well as in the prefrontal cortex, as reflected in the cognitive
      decline measured by CASI and TMT.

PMID- 22416827
TI  - Impaired instrumental activities of daily living affect conversion from mild
      cognitive impairment to dementia: the Osaki-Tajiri Project.
AB  - AIM: To determine whether impaired instrumental activities of daily living affect
      conversion from mild cognitive impairment to dementia for subjects in a
      community. METHODS: This is a 7-year retrospective study that followed 226
      randomly selected participants from the Prevalence Study 1998 in Tajiri in
      northern Japan who had Clinical Dementia Rating 0.5. Instrumental activities of
      daily living levels were assessed with a 21-item questionnaire. We analyzed the
      scores at baseline between the converters to dementia and non-converters.
      RESULTS: The converters had lower baseline scores on the 'bed making' and 'mode
      of transportation' items compared with the non-converters; the former item was
      significant after a stepwise logistic regression analysis that excluded age and
      Mini-Mental State Examination effects. In gender analysis, female converters had
      lower baseline scores on the 'bed making' and 'cleaning' items. For male
      participants, no items were found to have such an effect. CONCLUSIONS: We suggest
      that when individuals with mild cognitive impairment are limited in their
      performance of instrumental activities of daily living, this is predictive of
      dementia onset.

PMID- 22416828
TI  - Moderating effect of Islamic religiosity on the relationship between chronic
      medical conditions and psychological well-being among elderly Malays.
AB  - BACKGROUND: Research has found that physical health decline in later life is
      associated with poor psychological well-being. This study aimed to examine the
      possible moderating effect of Islamic religiosity on the relationship between
      chronic medical conditions and psychological well-being. METHODS: The sample for
      this study consisted of 1415 elderly Malay Muslims. It was obtained from a cross
      sectional survey entitled 'Patterns of Social Relationship and Psychological Well
      Being among Older Persons in Peninsular Malaysia', which conducted from 2007 to
      2009, using a multistage stratified sampling procedure. Data collection was
      performed through face-to-face interviews. A four-step moderated hierarchical
      regression analysis using SPSS software for Windows and the 'ModGraph-2' software
      program was used to test the hypothesis. RESULTS: Results of bivariate analysis
      showed, at certain levels of chronic medical conditions, older persons with a
      high level of religiosity reported significantly higher levels of psychological
      well-being compared to their counterparts with a low level of religiosity. Four
      step moderated hierarchical regression analysis revealed that the negative effect
      of chronic medical conditions on psychological well-being is reduced by both
      personal and social religiosity (beta = 0.07, P <= 0.01), after controlling for
      selected sociodemographic factors. CONCLUSION: Taken together, these findings
      indicate that the depressogenic effect of physical illness is decreased by
      religiosity in chronically ill elderly people. The implications and limitations
      of the current study are discussed and recommendations for future research are
      proposed.

PMID- 22416829
TI  - A case of serial nightmares and oneiroid state under paroxetine for senile
      depression.
AB  - We report on rare side effects of paroxetine. A 67-year-old female patient who
      had been suffering from prolonged depression for over a year but had not received
      appropriate treatment was administered 20-mg paroxetine daily. However, the
      patient required hospital admission after 16 days because of behavioural
      disturbances and delusions that she was being chased by evil persons from a
      religious group. The delusions were ultimately confirmed to be serial nightmares
      and an oneiroid state. The nightmares gradually disappeared following
      discontinuation of paroxetine. The Adverse Drug Reaction Probability Scale showed
      a score of 6 (probable). Reports on paroxetine-induced nightmares are rare, and
      there is a possibility that, in this case, parexetine caused the nightmares in
      association with depression and assumed underlying brain dysfunction due to
      ageing.

PMID- 22416830
TI  - Recurrent delusional ideas due to left caudate head infarction, without dementia.
AB  - Herein we report the case of a 77-year-old, right-handed man, without dementia,
      who had a cerebral infarction in the left caudate head that manifested recurrent
      delusional ideas. He experienced three episodes of delusional ideas; the first
      two occurred after loss of consciousness and the third after delirium at night.
      MRI findings of left caudate head infarction were the same for all three
      episodes. An unstable cerebral perfusion may have caused problems in the cerebral
      network between the caudate head and cerebral cortex. Decreased cerebral blood
      flow in the frontal lobe was noted particularly in the second and third episodes,
      supporting the neurological background of disinhibition of emotional behaviour.
      Antipsychotic drugs and a small dose of risperidone were effective in controlling
      the patient's delusional ideas.

PMID- 22416831
TI  - Lessons from genome-wide association studies findings in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder with a
      complex genetic background. Recent genome-wide association studies (GWAS) have
      placed important new contributors into the genetic framework of early- and late
      onset forms of this dementia. Besides confirming the major role of classic
      allelic variants (e.g. apolipoprotein E) in the development of AD, GWAS have thus
      far implicated over 20 single nucleotide polymorphisms in AD. In this review, we
      summarize the findings of 16 AD-based GWAS performed to date whose public
      registries are available at the National Human Genome Research Institute, with an
      emphasis on understanding whether the polymorphic markers under consideration
      support functional implications to the pathophysiological role of the major
      genetic risk factors unraveled by GWAS.

PMID- 22416833
TI  - A Bayesian inference of P(pi1 > pi2) for two proportions.
AB  - The statistical inference concerning the difference between two independent
      binominal proportions is often discussed in medical and statistical literature.
      However, such discussions are often based on the frequentist viewpoint rather
      than the Bayesian viewpoint. In this article, we propose an index theta =P(pi(1,
      post ) > pi(2, post )), where pi(1, post ) and pi(2, post ) denote binominal
      proportions following posterior density. We provide approximate and exact
      expressions for theta by using the beta prior. We also present the results of
      actual clinical trials to show the utility of theta. Our findings suggest that
      theta can potentially provide useful information in a clinical trial.

PMID- 22416832
TI  - Geriatric pharmacology and pharmacotherapy education for health professionals and
      students: a systematic review.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The rate of medication errors is high,
      and these errors can cause adverse drug reactions. Elderly individuals are most
      vulnerable to adverse drug reactions. One cause of medication errors is the lack
      of drug knowledge on the part of different health professionals. Medical
      curricula have changed in recent years, resulting in less education in the basic
      sciences, such as pharmacology. WHAT THIS STUDY ADDS: Our study shows that little
      curricular time is devoted to geriatric pharmacology and that educational
      programmes in geriatric pharmacology have not been thoroughly evaluated. While
      interest in pharmacology education has increased recently, this is not the case
      for geriatric pharmacology education. Education on geriatric pharmacology should
      have more attention in the curricula of health professionals, given the often
      complex pharmacotherapy in elderly patients. Educational topics should be related
      to the known risk factors of medication errors, such as polypharmacy, dose
      adjustments in organ dysfunction and psychopharmacotherapeutics. AIMS: Given the
      reported high rates of medication errors, especially in elderly patients, we
      hypothesized that current curricula do not devote enough time to the teaching of
      geriatric pharmacology. This review explores the quantity and nature of geriatric
      pharmacology education in undergraduate and postgraduate curricula for health
      professionals. METHODS: Pubmed, Embase and PsycINFO databases were searched (from
      1 January 2000 to 11 January 2011), using the terms 'pharmacology' and
      'education' in combination. Articles describing content or evaluation of
      pharmacology education for health professionals were included. Education in
      general and geriatric pharmacology was compared. RESULTS: Articles on general
      pharmacology education (252) and geriatric pharmacology education (39) were
      included. The number of publications on education in general pharmacology, but
      not geriatric pharmacology, has increased over the last 10 years. Articles on
      undergraduate and postgraduate education for 12 different health disciplines were
      identified. A median of 24 h (from 15 min to 4956 h) devoted to pharmacology
      education and 2 h (1-935 h) devoted to geriatric pharmacology were reported. Of
      the articles on education in geriatric pharmacology, 61.5% evaluated the teaching
      provided, mostly student satisfaction with the course. The strength of findings
      was low. Similar educational interventions were not identified, and evaluation
      studies were not replicated. CONCLUSIONS: Recently, interest in pharmacology
      education has increased, possibly because of the high rate of medication errors
      and the recognized importance of evidence-based medical education. Nevertheless,
      courses on geriatric pharmacology have not been evaluated thoroughly and none can
      be recommended for use in training programmes. Suggestions for improvements in
      education in general and geriatric pharmacology are given.

PMID- 22416834
TI  - Comparison of statistical models adjusting for baseline in the analysis of
      parallel-group thorough QT/QTc studies.
AB  - The ICH E14 guidance recommends the use of a time-matched baseline, while others
      recommend alternative baseline definitions including a day-averaged baseline. In
      this article we consider six models adjusting for baselines. We derive the
      explicit covariances and compare their power under various conditions. Simulation
      results are provided. We conclude that type I error rates are controlled.
      However, one model outperforms the others on statistical power under certain
      conditions. In general, the analysis of covariance (ANCOVA) model using a day
      averaged baseline is preferred. If the time-matched baseline has to be used as
      per requests from regulatory agencies, the analysis by time point using ANCOVA
      model should be recommended.

PMID- 22416835
TI  - Drug dosage individualization based on a random-effects linear model.
AB  - This article investigates drug dosage individualization when the patient
      population can be described with a random-effects linear model of a continuous
      pharmacokinetic or pharmacodynamic response. Specifically, we show through both
      decision-theoretic arguments and simulations that a published clinical algorithm
      may produce better individualized dosages than some traditional methods of
      therapeutic drug monitoring. Since empirical evidence suggests that the linear
      model may adequately describe drugs and patient populations, and linear models
      are easier to handle than the nonlinear models traditionally used in population
      pharmacokinetics, our results highlight the potential applicability of linear
      mixed models to dosage computations and personalized medicine.

PMID- 22416836
TI  - On sample size calculation for comparing survival curves under general hypothesis
      testing.
AB  - The log-rank test is commonly used to test the equivalence of two survival
      distributions under right censoring. Jung et al. (2005) proposed a modified log
      rank test for noninferiority trials and its corresponding sample size
      calculation. In this article, we extend the use of the modified log-rank test for
      clinical trials with various types of nonconventional study objectives and
      propose its sample size calculation under general null and alternative
      hypotheses. The proposed formula is so flexible that we can specify any survival
      distributions and accrual pattern. The proposed methods are illustrated with
      designing real clinical trials. Through simulations, the modified log-rank test
      and the derived formula for sample size calculation are shown to have
      satisfactory small sample performance.

PMID- 22416837
TI  - A novel method for assessing in vitro oncology drug combinations using growth
      rates.
AB  - We propose a new method that allows screening oncology drug combinations using
      data from in vitro studies to select agents that have the promise of showing a
      synergistic effect in vivo. In contrast to known approaches that define
      combination effects either on the concentration scale or on the percent
      inhibition scale, we use the growth rate of treated cells as a primary indicator
      of treatment activity. The developed method is based on a novel statistical model
      that describes the growth of cancer cells that are subject to treatment with a
      combination of compounds. The model assumes a multicompartment cell population
      with transition rates between compartments modeled according to biochemical
      reaction properties, and cells in each compartment growing according to
      exponential law. This translates to a linear system of ordinary differential
      equations, whose solution is accurately approximated by a closed-form expression
      using rapid equilibrium assumptions. Special cases of the aforementioned model
      represent situations when the combination effect is absent or when the considered
      drugs act as the same compound. Assuming the normal distribution for the growth
      rate measurement error, we describe a formal statistical testing procedure to
      distinguish between different mechanisms of action for the considered compounds,
      and to test if a significant combination effect is being observed.

PMID- 22416838
TI  - Power comparison of summary measure, mixed model, and survival analysis methods
      for analysis of repeated-measures trials.
AB  - In two-group repeated-measures studies, a traditional statistical approach is to
      base analysis directly on the observed continuous measurements, using either
      summary measures or a mixed linear model. In some medical studies, however, an
      alternate approach has been taken: Declare the occurrence of an "event" when the
      sequence of measurements crosses a prespecified threshold, and compare the groups
      with respect to time to event using the log-rank test. This approach is appealing
      to clinicians, but clearly involves a loss of information and therefore
      statistical efficiency. The aim of this article is to quantify the degree of
      power loss in the context of the random line model. We also compare the summary
      measures approach to the random line approach. In regard to the efficiency loss
      with the survival analysis approach, we find that the loss ranges, depending on
      the location of the threshold, from moderate to dramatic. Using an optimally
      weighted log-rank test in place of the standard log-rank test leads to minimal
      gain in efficiency. In regard to analysis based on the original continuous
      measurements, for testing the slope a weighted summary measure appears to be the
      best overall choice, whereas for testing the intercept the maximum likelihood
      (ML) approach is typically much more efficient than the summary measures
      approach, although the efficiency of the ML approach can be compromised in
      studies with a small number of observation timepoints. These results have obvious
      implications for the choice of study design and analysis.

PMID- 22416839
TI  - Assessing interactions for fixed-dose drug combinations in tumor xenograft
      studies.
AB  - Statistical methods for assessing the joint action of compounds administered in
      combination have been established for many years. However, there is little
      literature available on assessing the joint action of fixed-dose drug
      combinations in tumor xenograft experiments. Here an interaction index for fixed
      dose two-drug combinations is proposed. Furthermore, a regression analysis is
      also discussed. Actual tumor xenograft data were analyzed to illustrate the
      proposed methods.

PMID- 22416840
TI  - Robust small-sample inference for fixed effects in general Gaussian linear
      models.
AB  - Although asymptotically, the empirical covariance estimator is consistent and
      robust with respect to the selection of the working correlation matrix, when the
      sample size is small, its bias may not be negligible. This article proposes a
      small sample correction for the empirical covariance estimator in general
      Gaussian linear models. Inference for the fixed effects based on the corrected
      covariance matrix is also derived. A two-way analysis of variance (ANOVA) model
      with repeated measures, which evaluates the effectiveness of a CB1 receptor
      antagonist, and a four-period crossover design, which assesses the treatment
      effect in subjects with intermittent claudication, serve as examples to
      illustrate the proposed and other investigated methods. Simulation studies show
      that the proposed method generally performs better than other bias-correction
      methods, including Mancl and DeRouen (2001), Kauermann and Carroll (2001), and
      Fay and Graubard (2001), in the investigated balanced designs.

PMID- 22416841
TI  - Dose as instrumental variable in exposure-safety analysis using count models.
AB  - Confounding bias often occurs in the analysis of the exposure-safety relationship
      due to confounding factors that have impacts on both drug exposure and safety
      outcomes. Instrumental variable (IV) methods have been widely used to eliminate
      or to reduce the bias in observational studies in, for example, epidemiology.
      Recently applications of IV methods can also be found in clinical trials to deal
      with problems such as treatment non-compliance. IV methods have rarely been used
      in pharmacokinetic/pharmacodynamic analyses in clinical trials, although in a
      randomized trial with multiple dose levels dose may be a powerful IV. We consider
      modeling the relationship between pharmacokinetics as a measure of drug exposure
      and risk of adverse events with Poisson regression models and dose as an IV. We
      show that although IV methods for nonlinear models are in general complex, simple
      approaches are available for the combination of Poisson regression models and
      routinely used dose-exposure models. We propose two simple methods that are
      intuitive and easy to implement. Both methods consist of two stages with the
      first stage fitting the dose-exposure model; then the fitted model is used in
      fitting the Poisson regression model in two different ways. The properties of the
      two methods are compared under several practical scenarios with simulation. A
      numerical example is used to illustrate an application of the methods.

PMID- 22416842
TI  - Testing equality of generalized treatment effects.
AB  - Recently, the concept of generalized treatment effect, defined as P(X > Y) where
      X and Y denote continuous outcome variables for treatment arm and control arm,
      respectively, has been proposed as an appropriate measure of treatment effect in
      clinical trials with parallel design. Compared to the mean difference, the
      generalized treatment effect has many advantages; for example, it is a scaleless
      measure and it does not change under monotonic transformations. This article
      investigates the problem of testing equality of generalized treatment effects
      among several clinical trials. The proposed approach follows the same vein as the
      generalized variable method for testing equality of several log-normal means
      proposed by Li (2009). Numerical study demonstrates that the proposed test has
      excellent type I error control for clinical trials with small to medium sample
      sizes. Robustness study shows that the proposed method performs reasonably for
      categorical data.

PMID- 22416843
TI  - A portfolio-based approach to optimize proof-of-concept clinical trials.
AB  - Improving proof-of-concept (PoC) studies is a primary lever for improving drug
      development. Since drug development is often done by institutions that work on
      multiple drugs simultaneously, the present work focused on optimum choices for
      rates of false positive (alpha) and false negative (beta) results across a
      portfolio of PoC studies. Simple examples and a newly derived equation provided
      conceptual understanding of basic principles regarding optimum choices of alpha
      and beta in PoC trials. In examples that incorporated realistic development costs
      and constraints, the levels of alpha and beta that maximized the number of
      approved drugs and portfolio value varied by scenario. Optimum choices were
      sensitive to the probability the drug was effective and to the proportion of
      total investment cost prior to establishing PoC. Results of the present
      investigation agree with previous research in that it is important to assess
      optimum levels of alpha and beta. However, the present work also highlighted the
      need to consider cost structure using realistic input parameters relevant to the
      question of interest.

PMID- 22416847
TI  - Identifying illness perception schemata and their association with depression and
      quality of life in cardiac patients.
AB  - The purpose of this paper is to identify groups of cardiac patients who share
      similar perceptions about their illness and to examine the relationships between
      these schemata and psychosocial outcomes such as quality of life and depression.
      A total of 190 cardiac patients with diagnoses of myocardial infarction, stable
      angina pectoris or chronic heart failure, completed a battery of psychosocial
      questionnaires within four weeks of their admission to hospital. These included
      the Brief Illness Perceptions Questionnaire (BIPQ), Beck Depression Inventory II
      (BDI II) and The MacNew Health-related Quality of Life instrument (MacNew). BIPQ
      items were subjected to latent class analysis (LCA) and the resulting groups were
      compared according to their BDI II and MacNew scores. LCA identified a five-class
      model of illness perception which comprised the following: (1) Consequence
      focused and mild emotional impact, n = 55, 29%; (2) Low illness perceptions and
      low emotional impact, n = 45, 24%; (3) Control focused and mild emotional impact,
      n = 10, 5%; (4) Consequence focused and high emotional impact, n = 60, 32%; and
      (5) Consequence focused and severe emotional impact, n = 20, 10%. Gender and
      diagnosis did not appear to reflect class membership except that class 2 had a
      significantly higher proportion of AMI patients than did class 5. There were
      numerous significant differences between classes in regards to depression and
      health-related quality of life. Notably, classes 4 and 5 are distinguished by
      relatively high BDI II scores and low MacNew scores. Identifying classes of
      cardiac patients based on their illness perception schemata, in hospital or
      shortly afterwards, may identify those at risk of developing depressive symptoms
      and poor quality of life.

PMID- 22416848
TI  - Polysubstituted piperidines via iodolactonization: application to the asymmetric
      synthesis of (+)-pseudodistomin D.
AB  - Conjugate addition of lithium (S)-N-allyl-N-(alpha-methyl-p-methoxybenzyl)amide
      to methyl (E,E)-hepta-2,5-dienoate furnished the corresponding beta-amino ester.
      N-Protecting group manipulation, ring-closing metathesis, and ester hydrolysis
      gave enantiopure [N(1')-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridin-2'
      yl]ethanoic acid. Subsequent iodolactonization gave a bicyclic iodolactone
      scaffold. This key intermediate was elaborated to (+)-pseudodistomin D [in >99%
      ee and 7% yield over 16 steps from methyl (E,E)-hepta-2,5-dienoate].

PMID- 22416849
TI  - Effect of gender and race on the week 48 findings in treatment-naive, HIV-1
      infected patients enrolled in the randomized, phase III trials ECHO and THRIVE.
AB  - OBJECTIVES: A week 48 efficacy and safety analysis with respect to gender and
      race was conducted using pooled data from the phase III, double-blind, double
      dummy efficacy comparison in treatment-naive, HIV-infected subjects of TMC278 and
      efavirenz (ECHO) and TMC278 against HIV, in a once-daily regimen versus efavirenz
      (THRIVE) trials. METHODS: Treatment-naive, HIV-1-infected adults were randomized
      to receive rilpivirine (RPV; TMC278) 25 mg once a day (qd), or efavirenz (EFV)
      600 mg qd, plus tenofovir/emtricitabine (ECHO) or tenofovir/emtricitabine,
      zidovudine/lamivudine or abacavir/lamivudine (THRIVE). RESULTS: A total of 1368
      participants (76% male and 61% White, of those with available race data) were
      randomized and treated. No gender-related differences in response rate
      (percentage of patients with HIV-1 viral load < 50 HIV-1 RNA copies/mL, using an
      intent-to-treat, time-to-loss-of-virological-response algorithm) were observed
      (RPV: men, 85%; women, 83%; EFV: men, 82%; women, 83%). Response rates were lower
      in Black compared with Asian and White participants (RPV: 75% vs. 95% and 85%,
      respectively; EFV: 74% vs. 93% and 83%, respectively); this finding was mostly a
      result of higher discontinuation and virological failure rates in Black patients.
      Safety findings were generally similar across race and gender subgroups. However,
      nausea occurred more commonly in women than in men in both treatment groups. In
      men, diarrhoea was more frequent in the EFV group, and abnormal dreams/nightmares
      were more frequent in men in both the EFV and RPV groups. CONCLUSIONS: Overall
      response rates were high for both RPV and EFV. No gender differences were
      observed. However, response rates were lower among Black patients, regardless of
      treatment group. Gender appeared to influence the incidence of gastrointestinal
      adverse events and abnormal dreams/nightmares for both treatments.

PMID- 22416850
TI  - The effect of ethanol on the formation of N2-ethylidene-dG adducts in mice:
      implications for alcohol-related carcinogenicity of the oral cavity and
      esophagus.
AB  - The present study aimed to experimentally confirm that long-term alcohol drinking
      causes a high risk of oral and esophageal cancer in aldehyde dehydrogenase 2
      (ALDH2)-deficient individuals. Aldh2 knockout mice, an animal model of ALDH2
      deficiency, were treated with 8% ethanol for 14 months. Levels of acetaldehyde
      derived DNA adducts were increased in esophagus, tongue and submandibular gland.
      Our finding that a lack of Aldh2 leads to more DNA damage after chronic ethanol
      treatment in mice supports epidemiological findings on the carcinogenicity of
      alcohol in ALDH2-deficient individuals who drink chronically.

PMID- 22416851
TI  - Fear of suffocation alters respiration during obstructed breathing.
AB  - We aimed to investigate whether fear of suffocation predicts healthy persons'
      respiratory and affective responses to obstructed breathing as evoked by
      inspiratory resistive loads. Participants (N = 27 women, ages between 18 and 21
      years) completed the Fear of Suffocation scale and underwent 16 trials in which
      an inspiratory resistive load of 15 cmH(2)O/l/s (small) or 40 cmH(2)O/l/s (large)
      was added to the breathing circuit for 40 s. Fear of suffocation was associated
      with higher arousal ratings for both loads. Loaded breathing was associated with
      a decrease in minute ventilation, but progressively less so for participants
      scoring higher on fear of suffocation when breathing against the large load. The
      present findings document a potentially panicogenic mechanism that may maintain
      and worsen respiratory discomfort in persons with fear of suffocation.

PMID- 22416852
TI  - Association between bilirubin and cardiovascular disease risk factors: using
      Mendelian randomization to assess causal inference.
AB  - BACKGROUND: Elevated serum bilirubin has been associated with reduced risk of
      cardiovascular disease (CVD). However, serum bilirubin is also related with
      several potential confounders related to CVD, such as obesity. Mendelian
      randomization has been proposed as a method to address challenges to validity
      from confounding and reverse causality. It utilizes genotype to estimate causal
      relationships between a gene product and physiological outcomes. In this report,
      we demonstrate its use in assessing direct causal relations between serum
      bilirubin levels and CVD risk factors, including obesity, cholesterol, measures
      of vascular function and blood pressure. METHODS: Study subjects included 868
      asymptomatic individuals. Study subjects were genotyped at the UGT1A1*28 locus,
      which is strongly associated with bilirubin levels. RESULTS: Serum bilirubin
      levels were inversely associated with levels of several cardiovascular disease
      risk factors, including body mass index (p=0.003), LDL (p=0.0005) and total
      cholesterol (p=0.0002). In contrast, UGT1A1*28 genotype, a known cause of
      elevated bilirubin levels, was not significantly associated with any of these
      traditional CVD risk factors. We did observe an association between genotype and
      brachial artery diameter (p=0.003) and cold pressor reactivity (p=0.01).
      CONCLUSIONS: Our findings imply that the observed association of serum bilirubin
      levels with body mass index and cholesterol are likely due to confounding and
      suggest that previously established CVD benefits of increased bilirubin may in
      part be mediated by the early regulation of vascular structure and reactivity.

PMID- 22416853
TI  - Inhibition of enzymatic browning of chlorogenic acid by sulfur-containing
      compounds.
AB  - The antibrowning activity of sodium hydrogen sulfite (NaHSO(3)) was compared to
      that of other sulfur-containing compounds. Inhibition of enzymatic browning was
      investigated using a model browning system consisting of mushroom tyrosinase and
      chlorogenic acid (5-CQA). Development of brown color (spectral analysis), oxygen
      consumption, and reaction product formation (RP-UHPLC-PDA-MS) were monitored in
      time. It was found that the compounds showing antibrowning activity either
      prevented browning by forming colorless addition products with o-quinones of 5
      CQA (NaHSO(3), cysteine, and glutathione) or inhibiting the enzymatic activity of
      tyrosinase (NaHSO(3) and dithiothreitol). NaHSO(3) was different from the other
      sulfur-containing compounds investigated, because it showed a dual inhibitory
      effect on browning. Initial browning was prevented by trapping the o-quinones
      formed in colorless addition products (sulfochlorogenic acid), while at the same
      time, tyrosinase activity was inhibited in a time-dependent way, as shown by pre
      incubation experiments of tyrosinase with NaHSO(3). Furthermore, it was
      demonstrated that sulfochlorogenic and cysteinylchlorogenic acids were not
      inhibitors of mushroom tyrosinase.

PMID- 22416855
TI  - Association of halo nevus/i and vitiligo in childhood: a retrospective
      observational study.
AB  - BACKGROUND: Although halo nevus (HN) is frequently observed, the relationship
      between vitiligo and HN in children has rarely been investigated. OBJECTIVES: To
      investigate the association between HN and vitiligo in children and understand if
      HN/HNi might be a risk factor for vitiligo. METHODS: Ninety-eight patients with
      only HN/HNi and 27 with HN/HNi and vitiligo were investigated for number and
      localization of HN/HNi, family history for HN/HNi and vitiligo and personal and
      family history for autoimmune or other diseases. A follow-up telephone interview
      was performed to investigate the evolution of HN/HNi and the possible onset of
      vitiligo and/or other diseases. RESULTS: In the HN/HNi and vitiligo group, HN/HNi
      and vitiligo had started almost simultaneously in 11 children; in nine, the onset
      of HN/HNi was followed by vitiligo after 6 months to 5 years; seven patients
      presented vitiligo first and HN/HNi after 3-9 years. Patients with associated
      vitiligo had, significantly more often, multiple HNi and a positive personal
      and/or family history of autoimmune thyroiditis compared with those with only
      HN/HNi. Follow-up longer than 5 years was available in 54/98 patients with only
      HN/HNi; two of them, both with multiple HNi, developed vitiligo. After follow-up,
      multiple HNi were noticed in 18/52 patients without vitiligo and in 9/11 of those
      in whom HN/HNi heralded vitiligo (s.s.). CONCLUSIONS: In patients with multiple
      HNi, the risk of vitiligo and other autoimmune diseases seems to be higher than
      in pediatric patients with a single HN; clinicians should pay particular
      attention to children with multiple HNi and personal or family history of
      autoimmune diseases.

PMID- 22416854
TI  - Traumatic brain injury-induced cognitive and histological deficits are attenuated
      by delayed and chronic treatment with the 5-HT1A-receptor agonist buspirone.
AB  - The aim of this study was to evaluate the potential efficacy of the serotonin(1A)
      (5-HT(1A)) receptor agonist buspirone (BUS) on behavioral and histological
      outcome after traumatic brain injury (TBI). Ninety-six isoflurane-anesthetized
      adult male rats were randomized to receive either a controlled cortical impact or
      sham injury, and then assigned to six TBI and six sham groups receiving one of
      five doses of BUS (0.01, 0.05, 0.1, 0.3, or 0.5 mg/kg) or saline vehicle (VEH,
      1.0 mL/kg). Treatments began 24 h after surgery and were administered
      intraperitoneally once daily for 3 weeks. Motor function (beam-balance/beam-walk
      tests) and spatial learning/memory (Morris water maze) were assessed on post
      operative days 1-5 and 14-19, respectively. Morphologically intact CA1/CA3 cells
      and cortical lesion volume were quantified at 3 weeks. No differences were
      observed among the BUS and VEH sham groups in any end-point measure and thus the
      data were pooled. Regarding the TBI groups, repeated-measures ANOVAs revealed
      that the 0.3 mg/kg dose of BUS enhanced cognitive performance relative to VEH and
      the other BUS doses (p<0.05), but did not significantly impact motor function.
      Moreover, the same dose conferred selective histological protection as evidenced
      by smaller cortical lesions, but not greater CA1/CA3 cell survival. No
      significant behavioral or histological differences were observed among the other
      BUS doses versus VEH. These data indicate that BUS has a narrow therapeutic dose
      response, and that 0.3 mg/kg is optimal for enhancing spatial learning and memory
      in this model of TBI. BUS may have potential as a novel pharmacotherapy for
      clinical TBI.

PMID- 22416856
TI  - Phylogenetic comparison of exonic US4, US7 and UL44 regions of clinical herpes
      simplex virus type 1 isolates showed lack of association between their anatomic
      sites of infection and genotypic/sub genotypic classification.
AB  - BACKGROUND: HSV-1 genome is a mosaic of recombinants. Clinical Herpes simplex
      virus -1 (HSV1) isolates were already genotyped as A, B and C types based on
      nucleotide variations at Unique Short (US) 4 (gG) and US 7 (gI) regions through
      phylogeny. Analysis of Glycoprotein C (gC) exon present on the Unique Long (UL)
      region had also revealed the existence of different genotypes. Glycoprotein C is
      mainly involved in initial viral attachment to heparan sulphate on host cell
      surface facilitating the virus's binding and penetration into cell. As the amount
      of heparan sulphate on the host cell surface varies according to the cell type,
      it is plausible that different genotypes bind differentially to cell types.
      Hence, this study was framed to determine the existence of novel genotypes/sub
      genotypes in the US or UL regions which could associate with clinical entities.
      RESULTS: All the twenty five isolates analyzed in this study were of genotype A
      as per their gG gene sequences. In case of gI gene, 16 out of 25 were found to be
      type A and the remaining nine were type B putative intergenic recombinants.
      Intragenic recombinations were also encountered in both the US genes, with gG
      possessing novel subgenotypes, arbitrarily designated A1 and A2. The 9 type B
      isolates of gI genes also branched out into 2 clades due to genetic variations.
      Glycoprotein C of UL region had two distinct genotypic clades alpha and beta,
      whose topological distribution was significantly different from that of the US
      region. Neither the US nor UL regions, however, showed any preference among the
      genotypes to a specific anatomic site of infection. Even the non synonymous
      variations identified in the functional domain of gC, were not confined to a
      particular genotype/clinical entity. CONCLUSION: The analyses of the US and UL
      regions of the HSV-1 genome showed the existence of variegated genotypes in these
      two regions. In contrary to the documented literature, in which Asian strains
      were concluded as more conserved than European ones, our study showed the
      existence of a higher degree of variability among Indian strains. However, the
      identified novel genotypes and subgenotypes were not found associated with
      clinical entities.

PMID- 22416858
TI  - Fullerenyl boronic esters: ferric perchlorate-mediated synthesis and
      functionalization.
AB  - Fullerenyl boronic esters have been prepared by a ferric perchlorate-promoted
      reaction of [60]fullerene with various arylboronic acids. The obtained fullerenyl
      boronic esters could undergo further functionalization with diols to afford C(60)
      fused dioxane/dioxepane derivatives. A possible reaction mechanism for the
      formation of fullerenyl boronic esters has been proposed.

PMID- 22416857
TI  - Relative risk of acute pancreatitis in initiators of exenatide twice daily
      compared with other anti-diabetic medication: a follow-up study.
AB  - AIMS: Previously, a retrospective cohort study found no increased risk of acute
      pancreatitis with current or recent use of exenatide twice daily compared with
      use of other anti-diabetic drugs. This follow-up study investigated incident
      acute pancreatitis, with the use of a different data source and analytic method,
      in patients exposed to exenatide twice daily compared with patients exposed to
      other anti-diabetic medications. METHODS: A large US health insurance claims
      database was used. Eligible patients had >= 9 months continuous enrollment
      without a claim for pancreatitis and a claim for a new anti-diabetic medication
      on or after 1 June 2005 to 31 March 2009. Cases of acute pancreatitis were
      defined as hospitalized patients with an Internation Classification of Disease 9
      code of 577.0 in the primary position. A discrete time survival model was used to
      evaluate the relationship between exenatide twice daily and acute pancreatitis.
      RESULTS: Of 482,034 eligible patients, 24,237 initiated exenatide twice daily and
      457,797 initiated another anti-diabetic medication. Initiators of exenatide twice
      daily had more severe diabetes compared with initiators of other anti-diabetic
      medications. After adjustments for propensity score, insulin and use of
      medication potentially associated with acute pancreatitis, the odds ratio with
      exenatide twice daily exposure was 0.95 (95% CI 0.65-1.38). A secondary analysis
      that examined current, recent and past medication exposure found no increased
      risk of acute pancreatitis with exenatide twice daily, regardless of exposure
      category. CONCLUSION: This study indicates that exposure to exenatide twice daily
      was not associated with an increased risk of acute pancreatitis compared with
      exposure to other anti-diabetic medications. These results should be interpreted
      in light of potential residual confounding and unknown biases.

PMID- 22416859
TI  - When serial prostate biopsy is recommended: most cancers detected are clinically
      insignificant.
AB  - Study Type - Disagnostic (exploratory cohort) Level of Evidence 2b. What's known
      on the subject? and What does the study add? Many patients undergo serial biopsy
      with a low rate of detection of prostate cancer, and the rate of detection
      declines as more biopsies are pursued. Furthermore, the clinical significance of
      detected cancer appears to decline as well. It is important to follow all
      possible methods to detect cancer; however, there should be a parallel
      consideration for the clinical value for detection of these tumours with low
      malignant potential. The present study investigated in detail the total rate of
      cancer detection in serial biopsy and how many of these were deemed clinically
      insignificant. Moreover, it addressed the impact of detecting premalignant
      lesions on further detection of cancer in serial biopsy. OBJECTIVE: Many patients
      pursue serial prostate biopsies after two consecutive negative biopsy sessions.
      The objective of this study is to determine the indications of serial prostate
      biopsy and to compare outcomes, including the risk of detecting clinically
      insignificant cancer using different biopsy protocols in this highly selected
      population. PATIENTS AND METHODS: * Most cases of prostate cancer are detected on
      initial or one repeat biopsy, but persistent suspicion of prostate cancer
      occasionally leads to serial biopsy, which we define as more than two biopsy
      sessions. We recently showed that transrectal saturation biopsy (sPBx)
      significantly increases cancer detection when compared with extended schemes
      (ePBx) in the initial repeat biopsy (second overall biopsy) population, and that
      most cases identified are clinically significant. * In the past decade, 479 men
      underwent 749 repeat prostate biopsies after two prior negative biopsy sessions.
      * The ePBx group included 347 biopsies with 10-14 cores. * The sPBx group
      included 402 biopsies with >20 cores. * We analysed overall cancer detection and
      risk of detecting clinically significant vs insignificant tumours. RESULTS:
      Prostate cancer was detected in 15.9% of 749 serial biopsies, representing a
      cumulative prostate cancer detection rate of 24.8% (119/479 patients). * The sPBx
      group had a significantly higher detection rate per biopsy session (18.6% vs
      12.7%, P= 0.026). * Nevertheless, most positive biopsies 75/119 (63%) revealed
      clinically insignificant cancer, including 74.6% of cancers detected by sPBx.
      CONCLUSION: In men with two prior negative prostate biopsies, prostate cancer
      detection remains low regardless of clinical indication or transrectal biopsy
      protocol; most cancers identified are clinically insignificant, suggesting the
      threshold to repeat biopsy after more than one negative session should be very
      high.

PMID- 22416860
TI  - Monitoring and physical-chemical modeling of conditions of natural surface and
      underground waters forming in the Kola North.
AB  - Processes of surface and underground water forming in the Khibiny massif have
      been studied using a physical-chemical model of the "water-rock-atmosphere
      organic substance" system. The obtained model solutions are indicative of the
      fact that formation of surface and underground water of the Khibiny massif takes
      place on the whole in the framework of the considered system without attracting a
      hypothetical outside source of pollutants. The results are of practical and
      methodological importance for assessment of prediction of the man-induced impact
      on water systems in conditions of Subarctic.

PMID- 22416861
TI  - Tritium concentration analysis in atmospheric precipitation in Serbia.
AB  - Tritium activity concentration were monitored in monthly precipitation at five
      locations in Serbia (Meteorological Station of Belgrade at Zeleno Brdo, Vinca
      Institute of Nuclear Sciences, Smederevska Palanka, Kraljevo and Nis) over 2005,
      using electrolytic enrichment and liquid scintillation counting. The obtained
      concentrations ranged from 3.36 to 127.02 TU. The activity values obtained in
      samples collected at Zeleno Brdo were lower or close to the minimum detectable
      activity (MDA), which has a value of 3.36 TU. Significantly higher tritium levels
      were obtained in samples collected in Vinca Institute of Nuclear Sciences
      compared with samples from the other investigated locations. Amount of
      precipitation were also recorded. A good linear correlation (r = 0.75) for Zeleno
      Brdo and VINS between their tritium activity was obtained. It was found that the
      value of the symmetrical index n (which indicates the magnitude of tritium
      content changes with time (months) through its second derivative) is the highest
      for Vinca Institute of Nuclear Sciences compared to other locations, which is in
      accordance with the fact that the highest concentrations of tritium were obtained
      in the samples from the cited place.

PMID- 22416862
TI  - The radiochemical contamination (210Po and 238U) of zone around phosphogypsum
      waste heap in Wislinka (northern Poland).
AB  - The aim of this work was the determination of the impact of phosphogypsum waste
      heap in Wislinka (northern Poland) for radiological protection of zone around
      waste heap. These studies are very important for the estimation of natural alpha
      radionuclides contents in the vicinity of phosphogypsum waste heap and for
      environmental pollution assessment of this area. The process of bioaccumulation
      of radionuclides in interior plants parts prove to examine their origin sources,
      too. The activity of (210)Po, (234)U, and (238)U were measured using an alpha
      spectrometer. The values of uranium and polonium concentration in water with
      immediate area of waste heap are considerably higher than in the waters of the
      Martwa Wisla river. The values of activity ratio (234)U/(238)U are approximately
      about one in the phosphogypsum (0.97 +/- 0.05) and in the water of retention
      reservoir and pumping station (0.92 +/- 0.01 and 0.99 +/- 0.08), while in the
      water from the Martwa Wisla river they are slightly higher than one (1.03 +/-
      0.07 and 1.17 +/- 0.06). In the analyzed plants species the highest amounts of
      polonium and uranium were found in ruderal plants samples (between 51 +/- 1 and
      89 +/- 1 for (210)Po; between 36 +/- 3 and 68 +/- 3 for (238)U) as well as
      hygrophilous plant samples (18 +/- 1 and 84 +/- 3; 42 +/- 2 and 130 +/- 4,
      respectively for (210)Po and (238)U). The more amounts of (210)Po and (238)U
      radionuclides were accumulated mainly in the roots of plant species in comparison
      to green parts. The general conclusion of realized study is higher influence of
      phosphogypsum on radioactive contamination of environmental zone around heap
      waste in Wislinka (northern Poland).

PMID- 22416863
TI  - Levels and sources of planar and non-planar PCBs in pine needles across Poland.
AB  - Under a small project, one-year-old Scots Pine needles collected from 25
      spatially distant sites were examined in monitoring the extent of environmental
      diffusion and possible sources of polychlorinated biphenyls (PCBs) in ambient
      air, their depositions and uptake by plants in Poland. The congener-specific
      determination of planar and non-planar chlorobiphenyls was achieved by isotope
      dilution HRGC-HRMS method after a highly refined extraction on multi-layer column
      of silica gel and alumina layer and clean-up, and fractionations, followed by
      Hypercarb-HPLC and PYE-HPLC sub-fractionation steps. Contents of 117
      chlorobiphenyls determined in pine needles varied for the 25 sites studied and is
      between 2.7 and 49 ng/g wet weight. The PCBs pollution and congener-specific
      composition of pine needles to some degree varied according to the site or region
      surveyed depending on population density and industrialization. Many of the
      country-side areas showed lower concentrations between 2.7 and 8.9 ng/g ww. Pine
      needles in areas close to well populated and industrial regions of Opole, Kutno,
      Wloclawek and Debica showed the highest PCB pollution with concentrations varying
      between 30 and 49 ng/g ww. The Kutno site showed the highest pollution and this
      fact probably can be explained by possible emission from transformer manufactures
      located at some distance west of the Kutno area. Factor analysis (FA) and
      depending on the site revealed on relationship of PCBs composition of pine
      needles both with highly chlorinated PCB constituents of the mixtures such as
      Chlorofen, Aroclor 1254, Aroclor 1268 and Sovol but also of lower chlorinated PCB
      constituents of Aroclor 1242, Aroclor 1248, Clophen A40 or Delor 103. Thermal
      processes were considered a less significant source of PCBs in ambient air over
      Poland compared to evaporative sources related to technical PCB formulations.
      Supplemental materials are available for this article. Go to the publisher's
      online edition of Journal of Environmental Science and Health: Part A to view the
      free supplemental file.

PMID- 22416864
TI  - Estimation of the physicochemical properties of PCDD/Fs using three-dimensional
      holographic vector of atomic interaction field.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) are a group of
      important persistent organic pollutants. In the present study, the three
      dimensional holographic vector of atomic interaction field (3D-HoVAIF) method is
      used to describe the chemical structures of PCDD/Fs. After variable screening
      using a stepwise multiple regression (SMR) technique, the linear relationships
      among six physicochemical properties of PCDD/Fs and 3D-HoVAIF descriptors are
      built using a partial least-squares (PLS) regression model. The results show that
      the 3D-HoVAIF descriptors can be used to express the quantitative structure
      property relationships of PCDD/Fs. The predictive capabilities of the models have
      also been confirmed by leave-one-out cross-validation. The optimum model has been
      used to estimate values for PCDD/Fs for which no experimental data on
      physicochemical properties are available. Supplemental materials are available
      for this article. Go to the publisher's online edition of Journal of
      Environmental Science and Health: Part A to view the free supplemental file.

PMID- 22416865
TI  - Treatment of waste H2SO4 with Mg-Al oxide obtained by calcination of NO3-
      intercalated Mg-Al layered double hydroxide: Kinetics and equilibrium.
AB  - Mg-Al oxide obtained by calcination of NO(3)(-)-intercalated Mg-Al layered double
      hydroxide (NO(3)*Mg-Al LDH) was used to treat H(2)SO(4), acting as both a
      neutralizer of the acid and a fixative for SO(4)(2-). The fraction of SO(4)(2-)
      removed increased with time and with increasing Mg-Al oxide quantity and
      temperature. The rate of SO(4)(2-) removal followed first-order kinetics with
      apparent rate constants of 2.0 * 10(-3), 4.4 * 10(-3), and 5.3 * 10(-2) min(-1)
      at 10, 30, and 60 degrees C, respectively. The apparent activation energy was
      52.1 kJ mol(-1), confirming that the SO(4)(2-) removal by Mg-Al oxide proceeded
      under chemical reaction control. Furthermore, the adsorption isotherm of SO(4)(2
      ) by Mg-Al oxide obeyed the Langmuir equation. The maximum adsorption amount was
      2.0 mmol g(-1), or 4.0 meq g(-1), indicating that Mg-Al oxide has a large
      capacity for uptake of SO(4)(2-) from H(2)SO(4).

PMID- 22416866
TI  - Electrode effects on temporal changes in electrolyte pH and redox potential for
      water treatment.
AB  - The performance of electrochemical remediation methods could be optimized by
      controlling the physicochemical conditions of the electrochemical redox system.
      The effects of anode type (reactive or inert), current density and electrolyte
      composition on the temporal changes in pH and redox potential of the electrolyte
      were evaluated in divided and mixed electrolytes. Two types of electrodes were
      used: iron as a reactive electrode and mixed metal oxide coated titanium (MMO) as
      an inert electrode. Electric currents of 15, 30, 45 and 60 mA (37.5 mA L(-1), 75
      mA L(-1), 112.5 mA L(-1) and 150 mA L(-1)) were applied. Solutions of NaCl,
      Na(2)SO(4) and NaHCO(3) were selected to mimic different wastewater or
      groundwater compositions. Iron anodes resulted in highly reducing electrolyte
      conditions compared to inert anodes. Electrolyte pH was dependent on electrode
      type, electrolyte composition and current density. The pH of mixed-electrolyte
      was stable when MMO electrodes were used. When iron electrodes were used, the pH
      of electrolyte with relatively low current density (37.5 mA L(-1)) did not show
      significant changes but the pH increased sharply for relatively high current
      density (150 mA L(-1)). Sulfate solution showed more basic and relatively more
      reducing electrolyte conditions compared to bicarbonate and chloride solution.
      The study shows that a highly reducing environment could be achieved using iron
      anodes in divided or mixed electrolytes and the pH and redox potential could be
      optimized using appropriate current and polarity reversal.

PMID- 22416867
TI  - Quantitative bacteriological assessment of aerobic wastewater treatment quality
      and plant performance.
AB  - The application of a novel method for measuring changes in defined bacterial
      populations during aerobic wastewater treatment was investigated. Changes in
      bacterial communities and total active cells can be used as surrogates for
      identifying potential WWTP treatment train efficiency and operational performance
      malfunctions. In this study, the quantities of active heterotrophic aerobic
      bacteria (HAB) in weekly wastewater samples collected from twelve locations
      across a WWTP were determined colorimetrically using biological activity reaction
      tests (BART). Samples were collected for 2 months from primary, secondary and
      tertiary unit processes. The results show a mean HAB population decrease of 99.8%
      from primary influent to tertiary effluent, with the largest reductions occurring
      in the secondary aerobic lagoons. The results were reproducible and robust
      supporting the applied BART analytical method as an indicator not only of overall
      efficacy of the WWTP processes but also of potential WWTP process malfunctions.

PMID- 22416868
TI  - Development of an attached growth reactor for NH4-N removal at a drinking water
      supply system in Kathmandu Valley, Nepal.
AB  - Higher concentrations of ammonium (NH(4)-N) and iron (Fe) than a standard for
      drinking are typical characteristics of groundwater in the study area. To remove
      NH(4)-N and Fe, the drinking water supply system in this study consists of a
      series of treatment units (i.e., aeration and sedimentation, filtration, and
      chlorination); however, NH(4)-N in treated water is higher than a standard for
      drinking (i.e., <1.5 mg NH(4)-N/L). The objective of this study, therefore, is to
      develop an attached growth system containing a fiber carrier for reducing NH(4)-N
      concentration within a safe level in the treated water. To avoid the need of air
      supply for nitrification, groundwater was continuously dripped through the
      reactor. It made the system simple operation and energy efficient. Effects of
      reactor design (reactor length and carrier area) were studied to achieve a high
      NH(4)-N removal efficiency. In accordance with raw groundwater characteristics in
      the area, effects of low inorganic carbon (IC) and phosphate (PO(4)-P) and high
      Fe on the removal efficiency were also investigated. The results showed a
      significant increase in NH(4)-N removal efficiency with reactor length and
      carrier area. A low IC and PO(4)-P had no effect on NH(4)-N removal, whereas a
      high Fe decreased the efficiency significantly. The first 550 days operation of a
      pilot-scale reactor installed in the drinking water supply system showed a
      gradual increase in the efficiency, reaching to 95-100%, and stability in the
      performance even with increased flow rate from 210 to 860 L/day. The high
      efficiency of the present work was indicated because only less than 1 mg of NH(4)
      N/L was left over in the treated water.

PMID- 22416869
TI  - A fuzzy neural network model for monitoring A2/O process using on-line monitoring
      parameters.
AB  - An adaptive network based fuzzy inference system (ANFIS) model was employed to
      predict effluent chemical oxygen demand (COD(eff)) and ammonia nitrogen (NH(4)(+)
      (eff)) from an anaerobic/anoxic/oxic (A(2)/O) process, and meanwhile a self
      adapted fuzzy c-means clustering algorithm was used to identify the model's
      architecture and optimize fuzzy rules. When constructing the model or predicting,
      the on-line monitoring parameters, namely hydraulic retention time (HRT),
      influent pH (pH), dissolved oxygen in the aerobic reactor (DO) and mixed-liquid
      return ratio (r), were adopted as the input variables. Compared with the
      artificial neural network (ANN) model whose weight vector was optimized by a real
      code genetic algorithm (GA), the ANFIS presented better estimate performance.
      When predicting, the mean absolute percentage errors (MAPEs) of 1.8458% and
      2.8984% for COD(eff) and NH(4)(+) (eff) could be achieved using ANFIS; the root
      mean square errors (RMSEs) for COD(eff) and NH(4)(+) (eff) were 1.6317 and
      0.1291, respectively; the correlation coefficient (R) values of 0.9928 and 0.9951
      for COD(eff) and NH(4)(+) (eff) could also be achieved. The results indicated
      that reasonable monitoring A(2)/O process performance, just using on-line
      monitoring parameters, has been achieved through the ANFIS.

PMID- 22416871
TI  - Evaluation of evapotranspiration in small on-site HSF constructed wetlands.
AB  - Experimental results on evapotranspiration (ET), relevant to small on-site
      facilities are presented, derived from one-year controlled experiments in five
      pilot-scale horizontal subsurface flow (HSF) constructed wetlands (CW) used as
      lysimeters. The CW units operated in Northern Greece. They were rectangular tanks
      made of steel, with dimensions 3m long, 0.75m wide and 1m deep. Three different
      porous media were used, i.e., medium gravel, fine gravel and cobbles. Two plants
      were used, namely common reed (R, Phragmites australis) and cattails (C, Typha
      latifolia). One unit was unplanted. ET was estimated based on the water budget
      method. Conclusions were drawn on its relation to season and vegetation density.
      Furthermore, Pearson correlation coefficient analysis identified the main factors
      affecting wetland plant ET. Seven well-known ET empirical methods were applied to
      estimate ET using the measured meteorological and wetland data. ET estimated by
      the empirical methods were multiplied with appropriate correction coefficients to
      match measured ET, providing this way appropriate plant coefficient (K(c))
      values, and equations for predicting HSF CW evapotranspiration. The suitability
      of these methods for the particular constructed wetland type is discussed through
      comparison with the measured data. The Blaney-Criddle method was found as best.
      Furthermore, stepwise multiple linear regression analysis was used with the
      measured ET and meteorological data to produce simple empirical equations to
      predict ET rates according to meteorological factors, plant and substrate
      material.

PMID- 22416870
TI  - Deciphering the traits associated with PAH degradation by a novel Serratia
      marcesencs L-11 strain.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are wide spread industrial pollutants
      that are released into the environment from burning of coal, distillation of
      wood, operation of gas works, oil refineries, vehicular emission, and combustion
      process. In this study a lipolytic bacterium was isolated from mixed stover
      compost of Saccharum munja and Brassica campestris. This strain was identified by
      both classical and 16S ribosomal DNA sequencing method and designated as Serratia
      marcesencs L-11. HPLC-based quantitation revealed 39- 100% degradation of PAH
      compounds within seven days. Further its ability to produce catechol 1, 2
      dioxygenase (1.118 MUM mL(-1) h(-1)) and biosurfactants (0.88 g L(-1)) during
      growth in PAH containing medium may be responsible for its PAH-degradation
      potential. This novel bacterium with an ability to produce lipases, biosurfactant
      and ring cleavage enzyme can prove to be useful for in-situ degradation of PAH
      compounds.

PMID- 22416872
TI  - Using porous ceramic media in the upflow packed-bed reactor (UPBR) system for
      nitrogen removal via autotrophic nitrification and denitrification.
AB  - In this study, the feasibility of an innovative upflow packed-bed reactor (UPBR)
      system using porous sulfur and lime ceramic media (CERAMED-L and CERAMED-SL) to
      remove nitrogen for wastewater treatment was evaluated. The specific lime
      dissolution rates for CERAMEDs in the UPBRs show an inverse proportion to pH and
      resulted in 2.32 g as CaCO(3) kg(-1) CERAMED-L d(-1) and 1.64 g as CaCO(3) kg(-1)
      CERAMED-SL d(-1) at a pH 6.7. The calculated specific nitrification rate resulted
      1.73-2.29 kg NH(4)(+)-N m(-3) CERAMED-L d(-1), with a F/M ratio in the range 0.08
      0.31 g NH(4)(+)-N g(-1) VS d(-1). The alkalinity shortage in the feed solution
      seemed to be overcome by supplying specific alkalinity of 3.88 kg as CaCO(3) m(
      3) CERAMED-L d(-1) through the dissolution of lime from CERAMED-L. Autotrophic
      denitrification efficiencies were in the range of 83-96% during the test period,
      and the average specific denitrification rates of 0.97-1.92 kg NO(3)(-)N m(-3)
      CERAMED-SL d(-1) and 0.19-0.36 g NO(3)(-)-N g(-1) VS d(-1) were obtained.

PMID- 22416873
TI  - Phosphorus removal from domestic wastewater by Echinodorus cordifolius L.
AB  - This study was to use the plants to remove phosphorus from domestic wastewater
      which contained high phosphorus concentration. Six higher plant species such as
      Crinum asiaticum L., Echinodorus cordifolius L., Spathiphyllum clevelandii
      Schott, Rhizophora apiculata Blume, Thalia dealbata J.fraser., Heliconia
      psittacorum L.f. were screened for phosphorus removal. Plants were grown in the
      domestic wastewater and the remaining phosphorus-phosphate concentration in the
      systems was determined. The results indicated that among studied plants,
      Echinodorus cordifolius L. was the best for phosphorus removal. Using this plant
      will improve the quality of domestic wastewater which contained excess phosphorus
      concentration and induced eutrophication. The relationship between the plants,
      microorganisms, and soil in the system were also investigated. In this system,
      adsorption by soil was the major role for phosphorus removal (71%), followed by
      E. cordifolius (16%), microorganisms in domestic wastewater (7%), and
      microorganisms in soil (6%). These results indicated the ability of E.
      cordifolius to remove phosphorus which was superior to that of the microorganisms
      in the system. Moreover, the rapid phosphorus removal was concomitant to the
      growth, photosynthesis activity and biomass of E. cordifolius grown in domestic
      wastewater. The C:N:P ratio of E. cordifolius tissue in the system indicated that
      elements were taken up from the wastewater. From these results, the suitability
      of E. cordifolius for domestic wastewater treatment was confirmed.

PMID- 22416874
TI  - Survivin and laryngeal carcinoma prognosis: nuclear localization and expression
      of splice variants.
AB  - AIMS: Aberrant survivin expression in cancer cells has been associated with
      tumour progression, radiation/drug resistance and shorter patient survival. The
      aim of the present study was to investigate survivin expression in laryngeal
      carcinoma (LSCC) tissue and - for the first time at this site - the expression of
      survivin splice variants. P53 was also studied. METHODS AND RESULTS: Survivin and
      p53 expression was determined immunohistochemically in 86 consecutive patients
      operated for LSCC. Survivin mRNA expression was assessed by quantitative real
      time polymerase chain reaction (PCR). Hot-spot mutations in exons 5, 6, 7 and 8
      of the TP53 gene were studied by sequencing analysis. A nuclear localization for
      survivin predominated. There was a significant association between a higher
      nuclear survivin expression and LSCC recurrence (P = 0.046). Disease-free
      survival (DFS) for LSCC patients with a nuclear survivin expression >7.0% was
      shorter than in cases whose expression was <=7.0% (P = 0.05). Wild-type survivin
      correlated significantly with nuclear survivin expression (P = 0.02). p53
      expression was associated with the co-expression of wild-type survivin and
      survivin-2B (P = 0.01). CONCLUSIONS: Nuclear expression of survivin appears to
      influence LSCC aggressiveness, a higher nuclear survivin expression correlating
      with a higher recurrence rate and a shorter DFS. Wild-type survivin was the most
      frequently detected splice variant in LSCC tissues.

PMID- 22416875
TI  - Influences of personal standards and perceived parental expectations on worry for
      Asian American and White American college students.
AB  - The current study examined perceptions of living up to parental expectations
      (LPE) and personal standards as possible mediators of the relationship between
      ethnicity and worry in a sample of 836 Asian American and 856 White American
      college students. Asian Americans reported higher frequency of academic- and
      family-related worries, but they did not report higher levels of global tendency
      to worry. Perceptions of LPE of current academic performance and personal
      standards for preparation for a future career partially explained ethnic
      differences in frequency of academic worry. Personal standards and perceptions of
      LPE for respect for the family partially explained ethnic differences in
      frequency of family worry. The findings highlight the importance of targeting
      domain-specific personal standards and perceived parental expectations to reduce
      worry among Asian Americans.

PMID- 22416876
TI  - Plasma and synovial fluid connective tissue growth factor levels are correlated
      with disease severity in patients with knee osteoarthritis.
AB  - BACKGROUND: Connective tissue growth factor (CTGF) has been implicated in
      development of osteoarthritis (OA). OBJECTIVE: To determine the correlation
      between plasma and synovial fluid CTGF levels and the severity in knee
      osteoarthritis patients. METHODS: A total of 100 subjects were recruited into
      this study (75 OA patients and 25 controls). CTGF concentrations in plasma and
      synovial fluid were analyzed by enzyme-linked immunosorbent assay. RESULTS:
      Plasma and synovial fluid CTGF concentrations were correlated with radiographic
      severity. There was a positive correlation between plasma and synovial fluid CTGF
      levels. CONCLUSION: CTGF could be useful for monitoring the severity and
      progression of OA.

PMID- 22416877
TI  - Relationship between cortisol, life events and metabolic syndrome in men.
AB  - Psychological factors and stressful life events (LE) are considered to play a
      role in the onset of the metabolic syndrome (MS). We tested the association
      between LE and cortisol, a marker of chronic stress, with the risk of developing
      MS and their interaction. From a total number of 2906 men who completed a
      screening for the early detection of prostate cancer, 149 healthy men (mean +/-
      SD age, 58.6 +/- 7.7 years) were included in this study. Participants were
      assessed by the Holmes and Rahe questionnaire about their experience of LE during
      the previous 1-5 years. MS was diagnosed according to National Cholesterol
      Education Program-Adult Treatment Panel III (ATP-III) and International Diabetes
      Federation (IDF) criteria. Serum cortisol was measured at 08:00-09:00 h.
      Participants with MS (IDF criteria) reported significantly more past LE (p =
      0.009) and greater summed weight of LE (p = 0.049) than those without MS.
      Furthermore, LE interacted with cortisol in relation to MS: in men with increased
      serum cortisol levels ( >= 13.7 MUg/dl), number of LE significantly predicted MS
      status (relative risk (RR) = 1.16, p = 0.03), whereas in men with low cortisol,
      LE were unrelated to MS (p = 0.52). We conclude that LE were significantly more
      prevalent in men with the MS than without the MS, according to IDF criteria,
      independent of the effects of age and body mass index, especially in men with
      increased serum cortisol levels.

PMID- 22416879
TI  - Assessment methods for the evaluation of vitiligo.
AB  - There is no standardized method for assessing vitiligo. In this article, we
      review the literature from 1981 to 2011 on different vitiligo assessment methods.
      We aim to classify the techniques available for vitiligo assessment as
      subjective, semi-objective or objective; microscopic or macroscopic; and as based
      on morphometry or colorimetry. Macroscopic morphological measurements include
      visual assessment, photography in natural or ultraviolet light, photography with
      computerized image analysis and tristimulus colorimetry or spectrophotometry. Non
      invasive micromorphological methods include confocal laser microscopy (CLM).
      Subjective methods include clinical evaluation by a dermatologist and a vitiligo
      disease activity score. Semi-objective methods include the Vitiligo Area Scoring
      Index (VASI) and point-counting methods. Objective methods include software-based
      image analysis, tristimulus colorimetry, spectrophotometry and CLM. Morphometry
      is the measurement of the vitiliginous surface area, whereas colorimetry
      quantitatively analyses skin colour changes caused by erythema or pigment. Most
      methods involve morphometry, except for the chromameter method, which assesses
      colorimetry. Some image analysis software programs can assess both morphometry
      and colorimetry. The details of these programs (Corel Draw, Image Pro Plus,
      AutoCad and Photoshop) are discussed in the review. Reflectance confocal
      microscopy provides real-time images and has great potential for the non-invasive
      assessment of pigmentary lesions. In conclusion, there is no single best method
      for assessing vitiligo. This review revealed that VASI, the rule of nine and
      Wood's lamp are likely to be the best techniques available for assessing the
      degree of pigmentary lesions and measuring the extent and progression of vitiligo
      in the clinic and in clinical trials.

PMID- 22416878
TI  - Effect of misclassification of antiretroviral treatment status on the prevalence
      of transmitted HIV-1 drug resistance.
AB  - BACKGROUND: Estimates of the prevalence of transmitted HIV drug resistance (TDR)
      in a population are derived from resistance tests performed on samples from
      patients thought to be naive to antiretroviral treatment (ART). Much of the
      debate over reliability of estimates of the prevalence of TDR has focused on
      whether the sample population is representative. However estimates of the
      prevalence of TDR will also be distorted if some ART-experienced patients are
      misclassified as ART-naive. METHODS: The impact of misclassification bias on the
      rate of TDR was examined. We developed methods to obtain adjusted estimates of
      the prevalence of TDR for different misclassification rates, and conducted
      sensitivity analyses of trends in the prevalence of TDR over time using data from
      the UK HIV Drug Resistance Database. Logistic regression was used to examine
      trends in the prevalence of TDR over time. RESULTS: The observed rate of TDR was
      higher than true TDR when misclassification was present and increased as the
      proportion of misclassification increased. As the number of naive patients with a
      resistance test relative to the number of experienced patients with a test
      increased, the difference between true and observed TDR decreased. The observed
      prevalence of TDR in the UK reached a peak of 11.3% in 2002 (odds of TDR
      increased by 1.10 (95% CI 1.02, 1.19, p(linear trend) = 0.02) per year 1997-2002)
      before decreasing to 7.0% in 2007 (odds of TDR decreased by 0.90 (95% CI 0.87,
      0.94, p(linear trend) < 0.001) per year 2002-2007. Trends in adjusted TDR were
      altered as the misclassification rate increased; the significant downward trend
      between 2002-2007 was lost when the misclassification increased to over 4%.
      CONCLUSION: The effect of misclassification of ART on estimates of the prevalence
      of TDR may be appreciable, and depends on the number of naive tests relative to
      the number of experienced tests. Researchers can examine the effect of ART
      misclassification on their estimates of the prevalence of TDR if such a bias is
      suspected.

PMID- 22416880
TI  - Effect of processing and storage time on the contents of organosulfur compounds
      in pickled blanched garlic.
AB  - The influence of processing, with and without fermentation, on the contents of
      organosulfur compounds, namely, gamma-glutamyl peptides, S-alk(en)yl-L-cysteine
      sulfoxides (ACSOs), and S-allyl-L-cysteine (SAC), in pickled blanched garlic was
      evaluated. For each processing type, the effect of the preservation method and
      storage time was also analyzed. Blanching in hot water (90  degrees C for 5 min)
      hardly affected the individual organosulfur compound content. The fermentation
      and packing steps negatively affected the levels of all compounds except for SAC.
      The content of this compound increased during storage at room temperature whereas
      gamma-glutamyl peptides and ACSOs were degraded to various extents. The
      pasteurization treatment itself had no significant effect on the concentrations
      of organosulfur compounds. Use of the corresponding fermentation brine in the
      case of the fermented product in conjunction with refrigerated storage was found
      to be the best method to preserve the levels of organosulfur compounds in pickled
      garlic stored for up to one year.

PMID- 22416881
TI  - Lack of correlation between sealer penetration into dentinal tubules and
      sealability in nonbonded root fillings.
AB  - AIM: To determine the correlation between leakage and sealer penetration into
      dentinal tubule. METHODOLOGY: The root canal of 60 mandibular central incisor
      teeth were prepared and filled under standardized conditions. Teeth were placed
      into a device to assess glucose penetration using 15 psi pressure application.
      After 1 h, glucose concentrations in the lower chamber were measured using an
      enzymatic reaction. Each specimen was then sectioned horizontally at 3, 6 and 8
      mm from the apex, and a standard metallographic preparation was performed. The
      coronally facing surface of each slice was examined in a high-resolution
      stereomicroscope and under Confocal Laser Scanning Microscope. For each slice,
      the external outline of the root canal, the internal circumference of the root
      canal walls and the areas along the canal walls where the sealer had penetrated
      into the dentinal tubules (sealer tags) were outlined and measured. Afterwards,
      the percentage of the sealer penetration in each section was calculated. The
      Spearman correlation test was used to verify the correlation between the
      variables studied (glucose leakage and sealer penetration into dentinal tubules).
      RESULTS: The means and standard deviations of glucose leakage were 0.744 g L(-1)
      (+/-0.5), and the percentage of the dentinal tubule sealer penetration varied
      between teeth from 5.6% to 42.21%, with an average of 13.7 +/- 17.2%. The
      Spearman correlation test revealed no significant correlation between the two
      factors analysed (P = 0.082). The r(2) value was equal to 0.12. CONCLUSIONS:
      There was no significant correlation between sealability sealer penetration into
      dentinal tubules. The lack of correlation reported is of relevance as sealer
      penetration into dentinal tubules has been used as an advantageous property
      during the launch of new root filling materials and techniques.

PMID- 22416882
TI  - The effects of blood-draw and injection stimuli on the vasovagal response.
AB  - Vasovagal reactions (VVR) are common, complicating and deterring people from
      various medical procedures. A recent perspective (R. R. Diehl, ) suggests that
      VVR developed from the adaptive process of hemorrhagic fainting, perhaps as a
      means of preparing for anticipated blood loss. The primary goal of this study was
      to compare vasovagal symptoms during intravenous-injection and blood-draw videos.
      Sixty-two young adults watched the videos. Vasovagal symptoms were assessed with
      self-report, blood pressure, and heart rate variability. As predicted,
      participants reported more vasovagal symptoms and anxiety following the blood
      draw video. Sympathetic nervous system activity (low- to high-frequency ratio)
      decreased during both videos but significantly more during the blood-draw video,
      although this could be reversed by the Applied Tension technique. Results are
      discussed in terms of the relevance of specific stimuli and emotions in VVR.

PMID- 22416883
TI  - Mining for meaning: visualization approaches to deciphering Arabidopsis stress
      responses in roots and shoots.
AB  - Massive amounts of transcriptomic data documenting plant responses to changes in
      environment continue to accumulate in online databases. Unfortunately, many of
      these data sets have not been analyzed in full detail, especially those that
      involve time course experiments. To gain more knowledge of the successive gene
      expression events that occur when stress is initiated in one organ and then
      relayed to another, we have chosen stress response data for Arabidopsis shoots
      and roots from the detailed time course study of Killian et al. as a promising
      source to mine. Using refined statistical analysis, modified vector analysis, and
      a GO enrichment algorithm, more information was revealed concerning the effects
      of salt and UVB on gene expression events in shoots and roots over a 24-h time
      period. GeneMania, with in-house modifications, was used to further analyze
      abscisic acid (ABA) and jasmonic acid-related (JA) gene expression events in salt
      stressed roots and shoots. JA effects appeared to be quite distinct in roots when
      compared to shoots, especially with respect to the expression of members of the
      negative regulatory JAZ gene family. In contrast, ABA-related gene expression
      events were more similar in the two organs. Instances of crosstalk between
      hormones were observed, as were early responses of regulatory genes involved in
      both auxin and cytokinin signaling. In the case of each hormone class examined,
      hormone biosynthesis genes were coexpressed with the genes encoding negative
      regulators of the corresponding signaling pathway. Hypotheses to explain this
      finding and future experiments to further explore these nonlinear phenomena are
      proposed.

PMID- 22416884
TI  - Enhanced salt tolerance of tomatoes by exogenous salicylic acid applied through
      rooting medium.
AB  - In Tunisia, like in the other countries of the Mediterranean, tomato is ranked
      among the important vegetables in the economic sphere. Tunisia ranks as the first
      consumer of this vegetable in the world. However, tomatoes are exposed to
      multiple environmental stresses. In particular, salinity is the most stressful
      limiting factor to productivity. Salt tolerance of the tomato is susceptible to
      be ameliorated by genetic and physiologic ways. Salicylic acid (SA), a plant
      phenolic, is now considered as a hormone-like endogenous regulator, and its role
      in the defense mechanisms against biotic and abiotic stressors has been well
      documented. So, the aim of this study was to investigate the impact of exogenous
      application of SA (0.01 mM) on growth, nutritional behavior, and some metabolic
      parameters (total chlorophyll, soluble sugars, proline, and proteins) of tomato
      plants cv. Moneymaker exposed to NaCl (100 mM). Our results showed that the
      application of 0.01 mM SA to tomato plants via root drenching attenuate the
      depressive effect of salinity on plants. This amelioration results in stimulation
      of growth and development of plant. Under stress conditions, SA-treated plants
      exhibited more accumulation of photosynthetic pigments and K(+) contents. Thus,
      SA induces an increase in soluble sugars in roots and leaves; also, we noted the
      increase of proteins only in roots. Overall, the adverse effects of salt stress
      tomato plants were alleviated by the exogenous application of SA at vegetative
      stage, which upregulated nutrition and the accumulation of some organic solutes
      and osmoprotectors such sugars, proline, and proteins. So salicylic acid can be
      greatly used to enhance salt tolerance of tomato plants.

PMID- 22416885
TI  - Temporary targeted renal blood flow interruption using a reverse thermosensitive
      polymer to facilitate bloodless partial nephrectomy: a swine survival study.
AB  - What's known on the subject? and What does the study add? LumagelTM is a reverse
      thermosensitive polymer (RTP) that has previously been described in the
      literature as providing temporary vascular occlusion to allow for bloodless
      partial nephrectomy (PN) while maintaining blood flow to the untargeted portion
      of the kidney. At body temperature, LumagelTM has the consistency of a viscous
      gel but upon cooling rapidly converts to a liquid state and does not reconstitute
      thereafter. This property has allowed for it to be used in situations requiring
      temporary vascular occlusion. Previous experience with similar RTPs in coronary
      arteries proved successful, with no detectable adverse events. We have previously
      described our technique for temporary vascular occlusion of the main renal
      artery, as well as segmental and sub-segmental renal branches, to allow for
      bloodless PN in either an open or minimally invasive approach. These experiments
      were performed in the acute setting. This study is a two-armed survival trial to
      assess whether this RTP is as safe as hilar clamping for bloodless PN. Surviving
      animals showed normal growth after using the RTP, absence of toxicity, no organ
      dysfunction, and no pathological changes attributable to the RTP. We conclude
      that LumagelTM is as safe as conventional PN with hilar clamping, while adding
      the advantage of uninterrupted perfusion during renal resection. OBJECTIVE: To
      examine whether randomly selected regions of the kidney could undergo temporary
      flow interruption with a reverse thermosensitive polymer (RTP), LumagelTM
      (Pluromed, Inc., Woburn, MA, USA), followed by partial nephrectomy (PN), without
      adding risks beyond those encountered in the same procedure with the use of hilar
      clamping. MATERIALS AND METHODS: A two-armed (RTP vs hilar clamp), 6-week swine
      survival study was performed. Four swine underwent PN using hilar clamps, while
      six underwent PN with flow interruption using the RTP. The RTP, administered
      angiographically, was used for intraluminal occlusion of segmental or
      subsegmental arteries and was compared with main renal artery clamping with hilar
      clamps. The resection site was randomized for each swine. Laboratory studies were
      performed preoperatively, and at weeks 1, 3 and 6. Before killing the swine,
      repeat angiography was performed with emphasis on the site of previous flow
      interruption. Gross and microscopic examination of kidney, liver, lung, heart,
      skeletal muscle was later performed, and the vessel that had supported the
      previous plug was examined. RESULTS: All animals survived. No abnormal chemistry
      or haematology results were encountered over the 6 weeks. There were no surgical
      complications in either group. Using angiography we found 100% patency of vessels
      that had been occluded with the polymer 6 weeks previously for PN. The only gross
      or microscopic abnormalities were related to the renal resection and scar
      formation, and were similar in the two groups. CONCLUSION: Targeted flow
      interruption with the RTP added no additional risk to PN while allowing bloodless
      resection and uninterrupted flow to untargeted renal tissue.

PMID- 22416887
TI  - Brown dog tick (Rhipicephalus sanguineus) infestation of the penis detected by
      dermoscopy.

PMID- 22416886
TI  - Inclusion of a specific T cell epitope increases the protection conferred against
      foot-and-mouth disease virus in pigs by a linear peptide containing an
      immunodominant B cell site.
AB  - BACKGROUND: Foot-and-mouth disease virus (FMDV) causes an economically important
      and highly contagious disease of cloven-hoofed animals. FMD control in endemic
      regions is implemented using chemically inactivated whole-virus vaccines.
      Currently, efforts are directed to the development of safe and marked vaccines.
      We have previously reported solid protection against FMDV conferred by branched
      structures (dendrimeric peptides) harbouring virus-specific B and T-cell
      epitopes. In order to gain insights into the factors determining a protective
      immune response against FMDV, in this report we sought to dissect the
      immunogenicity conferred by different peptide-based immunogens. Thus, we have
      assessed the immune response and protection elicited in pigs by linear peptides
      harbouring the same FMDV B-cell or B and T-cell epitopes (B and TB peptides,
      respectively). RESULTS: Pigs were twice immunized with either the B-cell epitope
      (site A) peptide or with TB, a peptide where the B-cell epitope was in tandem
      with the T-cell epitope [3A (21-35)]. Both, B and TB peptides were able to induce
      specific humoral (including neutralizing antibodies) and cellular immune
      responses against FMDV, but did not afford full protection in pigs. The data
      obtained showed that the T-cell epitope used is capable to induce efficient T
      cell priming that contributes to improve the protection against FMDV. However,
      the IgA titres and IFNgamma release elicited by these linear peptides were lower
      than those detected previously with the dendrimeric peptides. CONCLUSIONS: We
      conclude that the incorporation of a FMDV specific T-cell epitope in the peptide
      formulation allows a significant reduction in virus excretion and clinical score
      after challenge. However, the linear TB peptide did not afford full protection in
      challenged pigs, as that previously reported using the dendrimeric construction
      indicating that, besides the inclusion of an adecuate T-cell epitope in the
      formulation, an efficient presentation of the B-cell epitope is crucial to elicit
      full protection by peptide vaccines.

PMID- 22416888
TI  - Novel aqueous nano-scaled formulations of oleic acid stabilized hydrophobic
      superparamagnetic iron oxide nanocrystals.
AB  - BACKGROUND: Novel aqueous nano-scaled formulations were developed for hydrophobic
      oleic acid stabilized monodisperse superparamagnetic magnetite nanocrystals.
      METHODS: In the study, single and mixed lipid amphiphiles based on Cremophor RH
      40 (Crem-RH-40), Solutol HS-15 (Sol-HS-15), Phospholipon-100H (PL-100H) and
      sucrose ester M-1695 (SE-M-1695) were employed at varying concentrations.
      Isotonicity and physiological pH adjustments were achieved by using 5% w/v
      mannitol in 10 mM pH 7.4 phosphate buffer. Mannitol also served as lyoprotectant
      for the freeze drying of selected formulation. The developed formulations were
      characterized by photon correlation spectroscopy (PCS) and asymmetric flow field
      flow fractionation methods for their size and size distributions and morphologies
      were examined by transmission electron microscopy (TEM). Moreover, the potential
      magnetic resonance imaging (MRI) contrast agent application of a selected
      formulation was investigated by (1)H-NMR relaxometric measurements. RESULTS: The
      results showed that stable formulations of the nanocrystals with hydrodynamic
      diameters generally below 100 nm were obtained. Among the developed formulations,
      the one prepared with 0.75% Crem-RH-40, 0.5% PL-100H and 0.25% SE-M-1695 had a
      mean hydrodynamic diameter of ~64 nm and zeta potential of -20 mV. This
      formulation exhibited low degree of aggregation, high level of incorporation of
      magnetite nanocrystals and very good stability profile over a period of 6 months.
      In addition, it showed transverse and longitudinal relaxivities of 221.8 and 32.1
      s(-1).mM(-1), respectively with r(2)/r(1) ratio of 6.9. CONCLUSION: This study
      revealed that mixed lipid-based amphiphiles allow stable aqueous formulations of
      the normally challenging hydrophobic magnetite nanocrystals with potential in
      vivo MRI contrast applications.

PMID- 22416889
TI  - Regiodivergent synthesis of functionalized indene derivatives via Pt-catalyzed
      Rautenstrauch reaction of propargyl carbonates.
AB  - A regiodivergent synthesis of functionalized indene derivatives from a Pt
      catalyzed Rautenstrauch reaction of propargyl carbonate is described. A one-pot
      Rautenstrauch/Tsuji-Trost reaction delivering 2-indanones was realized
      efficiently using this methodology.

PMID- 22416890
TI  - Patients' views of patient-centred care: a phenomenological case study in one
      surgical unit.
AB  - AIMS: To report a study of patients' views of patient-centred care. The study
      aimed to explore patients' understanding and conceptualization of patient-centred
      care and link it to existing literature on the topic. BACKGROUND: Patient-centred
      care currently lacks a widely accepted definition, with much of the literature
      based on definitions formulated by health professionals and researchers. DESIGN:
      Qualitative research study grounded in phenomenology. METHODS: Interpersonal
      interviews were conducted with ten participants who were patients in a surgical
      ward in a large metropolitan hospital in South Australia in 2010.
      RESULTS/FINDINGS: Participants were unfamiliar with the concept of patient
      centred care, but despite this, were able to describe what the term meant to them
      and what they wanted from their care. Patients equated the type and quality of
      care they received with the staff that provided it and themes of connectedness,
      involvement and attentiveness were prevalent in their descriptions of what they
      wanted from their care. CONCLUSION: Ensuring that patients have a voice in the
      definition and conceptualization of patient-centred care is essential and further
      and regular consultation with patients about their needs and priorities will
      ensure an integrated approach to patient-centred care.

PMID- 22416891
TI  - Voice onset time in Swedish children and adults.
AB  - Voice onset time (VOT) is a temporal acoustic parameter, which reflects the
      timing of speech motor control. The objective of the work was to obtain normative
      VOT data in Swedish children. Thus, 150 children aged 8-11 years old and 36
      adults were audio-recorded when producing the plosives in minimal pairs. Measures
      were made using waveforms and spectrograms. Results show that Swedish children
      developed adult-like VOT values between 9 and 10 years. By the age of 10 years
      prevoicing was also found to be completely adultlike in length. The results
      indicate that all Swedish adults do not produce voiced plosives with prevoicing.
      No evident gender differences were found. The obtained VOT values can be used as
      normative data when assessing children with speech and language disorders.

PMID- 22416892
TI  - Interactions of membrane active peptides with planar supported bilayers: an
      impedance spectroscopy study.
AB  - Membrane active peptides exert their biological effects by interacting directly
      with a cell's lipid bilayer membrane. These therapeutically promising peptides
      have demonstrated a variety of activities including antimicrobial, cytolytic,
      membrane translocating, and cell penetrating activities. Here, we use
      electrochemical impedance spectroscopy (EIS) on polymer-cushioned supported lipid
      bilayers constructed on single crystal silicon to study two pairs of closely
      related membrane active peptides selected from rationally designed, combinatorial
      libraries to have different activities in lipid bilayers: translocation,
      permeabilization, or no activity. Using EIS, we observed that binding of a
      membrane translocating peptide to the lipid bilayer resulted in a small decrease
      in membrane resistance followed by a recovery back to the original value. The
      recovery may be directly attributable to peptide translocation. A
      nontranslocating peptide did not decrease the resistance. The other pair, two
      membrane permeabilizing peptides, caused an exponential decrease of membrane
      resistance in a concentration-dependent manner. This permeabilization of the
      supported bilayer occurs at peptide to lipid ratios as much as 1000-fold lower
      than that needed to observe effects in vesicle leakage assays and gives new
      insights into the fundamental peptide-bilayer interactions involved in membrane
      permeabilization.

PMID- 22416893
TI  - First presentation for care of HIV-infected patients with low CD4 cell count in
      Lyon, France: risk factors and consequences for survival.
AB  - To identify the risk factors associated with presentation for care with CD4 cell
      count <= 200 cells/mm(3) and death in HIV-infected patients in Lyon, France. Data
      were analyzed on participants from mid-1992 to December 2006 in the Lyon section
      of the French Hospital Database on HIV Infection. Patients were stratified into
      two categories according to CD4 cell count at first presentation for care in
      University of Lyon hospitals: Group 1 (Gr1) patients with CD4 <= 200 cells/mm(3)
      and Group 2 (Gr2) patients with CD4 >200 cells/mm(3). Multivariate logistic
      regression assessed the risk factors associated with first presentation for care
      with CD4 <= 200 cells/mm(3). Survival was analyzed according to the Cox
      regression model. Among 3569 eligible patients (838 females and 2731 males, mean
      age: 36.3 +/- 10.3 years), 1139 (31.9%) were categorized as Gr1. The factors
      associated with first presentation for care with CD4 <= 200 cells/mm(3) were:
      older age, male gender, route of HIV transmission, migrant populations,
      geographical areas other than Rhone-Alpes, and access to care in 1992-1997.
      Overall mortality was higher in Gr1 than in Gr2 (24.4% [278/1139] vs. 4.1%
      [101/2430]; p<0.001). The risk of death was 5.81 [4.61-7.32] in Gr1 compared to
      Gr2. In addition to CD4 cell count, age and enrollment periods for care were
      factors independently related to death. Despite public health efforts in Lyon,
      one-third of HIV-infected patients reach the health care system with CD4 cell
      count <= 200 cells/mm(3), which was linked with higher mortality.

PMID- 22416894
TI  - Clinical differences between mass-forming autoimmune pancreatitis and pancreatic
      cancer.
AB  - OBJECTIVE: Autoimmune pancreatitis (AIP) needs to be differentiated from
      pancreatic cancer (PC). We aimed to clarify the findings specific for AIP by
      comparing the clinical differences between mass-forming AIP and PC. MATERIAL AND
      METHODS: We retrospectively compared 36 patients with mass-forming AIP and 60
      with PC without metastasis regarding clinical, imaging, serological, histological
      differences and other organ involvement (OOI). We evaluated the sensitivity,
      specificity and accuracy of these findings for the differential diagnosis between
      AIP and PC. RESULTS: The findings 100% specific for AIP were a capsule-like rim
      on computed tomography (CT), skipped lesion of main pancreatic duct (MPD) on
      endoscopic retrograde pancreatography (ERP) or magnetic resonance
      cholangiopancreatography (MRCP), gamma-globulin > 2 g/dl, OOI (extrapancreatic
      biliary stricture, salivary gland swelling and retroperitoneal fibrosis) and
      ruling out PC by histopathological findings of endoscopic ultrasonography-guided
      fine-needle aspiration. The findings over 90% specific were IgG4 > 280 mg/dl
      (98%), IgG > 1800 mg/dl (97%), maximal diameter of upstream MPD < 5 mm on MRCP
      (95%) and IgG4 > 135 mg/dl (94%), respectively. CONCLUSIONS: Clinical, imaging,
      serological, histological findings and OOI differed between mass-forming AIP and
      PC. Capsule-like rim on CT, skipped lesion of MPD on ERP or MRCP, IgG4 > 280
      mg/dl, and OOI were highly specific findings for AIP. These findings are useful
      in the differential diagnosis of mass-forming AIP from PC.

PMID- 22416895
TI  - Antibacterial activity of dentine and pulp extracellular matrix extracts.
AB  - AIM: To determine whether extracellular matrix (ECM) preparations from pulp
      (pECM) and dentine (dECM) possess antimicrobial activity. METHODOLOGY: Dentine
      and pulp ECM preparations were isolated with 10% ethylenediaminetetraacetic acid
      (EDTA), pH 7.2 and sequential use of 0.5mol L(-1) NaCl, pH 11.7 and 0.1mol L(-1)
      tartaric acid, pH 2.0, respectively, with protease inhibitor inclusion
      throughout. Antimicrobial activity against Streptococcus mutans, Streptococcus
      oralis and Enterococcus faecalis was assessed using turbidity as a measure of
      bacteria growth. The cytotoxicity of the extracts on primary pulp cells was also
      determined by lactate dehydrogenase (LDH) release. Statistical analysis of data
      was performed using paired student's t-tests. RESULTS: Extracellular matrix
      extracts from the pulp and dentine showed antibacterial activity against three
      types of anaerobic bacteria associated with dental disease (P< 0.05). The ECM
      extracts demonstrated no significant cytotoxic effect on pulpal cells at the
      concentrations used for antibacterial activity. CONCLUSIONS: The bacteriostatic
      antibacterial activity of pECM and dECM indicates that the release of these
      matrix molecules from pulp and dentine may contribute to defence responses during
      dental disease, treatment and repair.

PMID- 22416896
TI  - Does self monitoring of blood glucose as opposed to urinalysis provide additional
      benefit in patients newly diagnosed with type 2 diabetes receiving structured
      education? The DESMOND SMBG randomised controlled trial protocol.
AB  - BACKGROUND: The benefit of self-monitoring of blood glucose (SMBG) in people with
      type 2 diabetes on diet or oral agents other than sulphonylureas remains
      uncertain. Trials of interventions incorporating education about self-monitoring
      of blood glucose have reported mixed results. A recent systematic review
      concluded that SMBG was not cost-effective. However, what was unclear was whether
      a cheaper method of self-monitoring (such as urine glucose monitoring) could
      produce comparable benefit and patient acceptability for less cost.
      METHODS/DESIGN: The DESMOND SMBG trial is comparing two monitoring strategies
      (blood glucose monitoring and urine testing) over 18 months when incorporated
      into a comprehensive self-management structured education programme. It is a
      multi-site cluster randomised controlled trial, conducted across 8 sites (7
      primary care trusts) in England, UK involving individuals with newly diagnosed
      Type 2 diabetes.The trial has 80% power to demonstrate equivalence in mean HbA1c
      (the primary end-point) at 18 months of within +/- 0.5% assuming 20% drop out and
      20% non-consent. Secondary end-points include blood pressure, lipids, body weight
      and psychosocial measures as well as a qualitative sub-study.Practices were
      randomised to one of two arms: participants attend a DESMOND programme
      incorporating a module on self-monitoring of either urine or blood glucose. The
      programme is delivered by accredited educators who received specific training
      about equipoise. Biomedical data are collected and psychosocial scales completed
      at baseline, and 6, 12, and 18 months post programme. Qualitative research with
      participants and educators will explore views and experiences of the trial and
      preferences for methods of monitoring. DISCUSSION: The DESMOND SMBG trial is
      designed to provide evidence to inform the debate about the value of self
      monitoring of blood glucose in people with newly diagnosed type 2 diabetes.
      Strengths include a setting in primary care, a cluster design, a health economic
      analysis, a comparison of different methods of monitoring while controlling for
      other components of training within the context of a quality assured structured
      education programme and a qualitative sub-study. TRIAL REGISTRATION: ISRCTN:
      ISRCTN95696668.

PMID- 22416897
TI  - Methadone maintenance therapy outcomes in Iran.
AB  - INTRODUCTION: Because of the increasing number of injecting drug users (IDUs) in
      Iran and the risk of the spread of HIV infection, harm reduction programs have
      been considered for conventional law enforcement measures. The aim of this study
      was to evaluate the efficacy of methadone maintenance therapy (MMT) in IDUs and
      the associated health and social outcomes. MATERIAL AND METHODS: This case
      control study was conducted at the Persepolis Harm Reduction Center in Tehran
      during the year 2006. Data were gathered from two groups of randomly chosen
      patients. The first group consisted of 75 IDU patients who had undergone at least
      6 months of methadone treatment (the MMT group), and second group consisted of 75
      newly admitted clients (the control group). Participants were assessed on their
      dangerous injection and sexual behaviors, social well-being, and patterns of drug
      use. The results were compared between the two groups. RESULTS: The mean age of
      participants in the two groups was almost the same (34.28 years in the control
      group and 35.68 years in the MMT group, p >.05). Prevalence of drug injection in
      the MMT group was less than that in the control group (16% vs. 100%). There was
      also a dramatic difference in needle and syringe sharing (40% in the control
      group vs. 4% in the MMT group) but not in crimes and arrests (p = .4). Those in
      the MMT group had a better relationship with their families, partners, coworkers,
      and neighbors compared with controls. There was no considerable difference in
      dangerous sexual behaviors between the two groups. CONCLUSIONS: Given the large
      number of HIV-positive cases among IDUs and considering that injection drug use
      is the main spreading factor for HIV, MMT would play a major role in controlling
      the HIV epidemic through reduction of heroin injection and the risk behaviors
      related to it. High inflation rate, lack of interorganization coordination,
      budget limitation, and no follow-up were the most important limitations of this
      study.

PMID- 22416898
TI  - Successful use of cyclophosphamide, bortezomib, and dexamethasone to treat a case
      of relapsed POEMS.
AB  - POEMS syndrome is a rare paraneoplastic condition related to myeloma. Because it
      is rare, there is very little known about treatment options. The use of
      potentially neurotoxic chemotherapeutic drugs is of concern in a disease whose
      major manifestation is neuropathy. Herein, we describe an extraordinary response
      to the combination of cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in
      a patient with relapsed, life-threatening POEMS syndrome.

PMID- 22416899
TI  - Increased levels of COX-2 and oral lichen planus.

PMID- 22416900
TI  - Urethral pressure reflectometry; a novel technique for simultaneous recording of
      pressure and cross-sectional area: a study of feasibility in the prostatic
      urethra.
AB  - What's known on the subject? and What does the study add? In the 1980s and 1990s,
      a method for direct measurement of pressure and cross-sectional area in women and
      men was developed. It was successful in terms of obtaining meaningful results in
      several studies. But the technique, which was based on the field gradient
      principle, was never implemented in the clinical setting because of technical
      limitations. In 2005, urethral pressure reflectometry was introduced as a new
      technique in female urodynamics. The technique has been shown to be more
      reproducible than conventional urethral pressure profilometry, when measuring
      incontinence in women. In 2010 it was also introduced as a new measuring
      technique in the anal canal. This study, adds a new and interesting technique to
      the field of male urodynamics. For the first time, sound waves have been used to
      measure pressure and cross-sectional area simultaneously, directly in the
      prostatic urethra. The results from this first trial with urethral pressure
      reflectometry are promising, in terms of obtaining meaningful physiological
      parameters. Our hope is that, future trials will help us to be able to identify
      specific areas of obstruction or rigidity in the prostatic urethra, making
      treatment more direct and side effects from surgery less severe. However, further
      studies are needed to evaluate the technique with regards to clinical usefulness
      in men with benign prostatic obstruction. OBJECTIVE: Urethral Pressure
      Reflectometry (UPR) was introduced in 2005, and it has since been used in the
      female urethra for simultaneous measurement of pressure (P) and cross-sectional
      area (CA). It has shown to be more reproducible than conventional pressure
      measurement and reintroduced direct measurement of pressure and elastance in the
      urethra as important parameters when assessing incontinent women. To test the
      feasibility of UPR in the prostatic urethra. PATIENTS AND METHODS: We tested the
      technique in ten male patients, median age 73 and range 51-91. Measurements were
      performed in the supine position, with less than 50 ml of urine in the bladder.
      The UPR valuables measured were opening and closing pressure, opening and closing
      elastance and hysteresis. RESULTS: The PVC tube was easy to insert to the same
      degree as a normal KAD. Opening pressure and opening elastance were measured on
      all patients. The sphincter area was easily identified during measurements. UPR
      provides results compatible with previous techniques. A standardized method for
      measurements was developed. CONCLUSION: UPR has been shown feasible in the
      prostatic urethra. Further studies on healthy volunteers and patients with lower
      urinary tract symptoms and benign prostatic obstruction (BPO) are needed, to
      determine if UPR has a future role in urodynamic diagnostics of male patients
      with BPO.

PMID- 22416901
TI  - Neuromuscular failure is unlikely to explain the early exercise cessation in hot
      ambient conditions.
AB  - Baseline, postexercise (20 min cycling) and postexhaustion (incremental test)
      neuromuscular function was assessed in control (24 degrees C) and hot (40 degrees
      C) conditions. Heat affects the plantar flexors and knee extensors differently,
      but most of the effects of heat (e.g., M-wave decrement) and fatigue (e.g.,
      voluntary activation and H-reflex decrement) were independent of each other.
      However, peripheral fatigue of the knee extensors was lower at exhaustion in hot
      than neutral environment (peak twitch decrement from baseline to exhaustion: -19%
      vs. -33%, p < .05). In addition, heat had no negative effect on transcranial
      magnetic stimulation responses during cycling, and neuromuscular failure is
      unlikely to explain the early exercise cessation in the heat (13 min 50 s vs. 17
      min 9 s) that occurred when participants reached maximal perceived exertion (19.2
      vs. 19.1, ns) with higher core temperature (38.7 degrees C vs. 38.2 degrees C, p
      < .05) and heart rate (184 bpm vs. 179 bpm, p < .05).

PMID- 22416902
TI  - Low molecular weight heparin versus unfractionated heparin in cerebral venous
      sinus thrombosis: a randomized controlled trial.
AB  - BACKGROUND:   There is no randomized controlled trial (RCT) evaluating the
      efficacy and safety of low molecular weight heparin (LMWH) compared to
      unfractionated heparin (UFH) in cerebral venous sinus thrombosis (CVST). In this
      RCT, we have evaluated the efficacy and safety of LMWH versus UFH in CVST.
      METHODS:   Consecutive patients with CVST diagnosed on the basis of MR venography
      (MRV) who was free of bleeding diathesis, malignancy, hepatic or renal failure
      were prospectively enrolled. History, clinical findings and risk factors were
      evaluated. MRI and MRV findings were recorded. The patients were randomized to
      LMWH and UFH groups for 14 days followed by oral anticoagulant. The hospital
      mortality and 3 months outcome as assessed by Barthel index (BI) score were
      noted. RESULTS:   32 patients received UFH and 34 received LMWH. The baseline
      demographic, clinical and radiological parameters were similar in both the
      groups. Six patients died and all were in UFH group (P = 0.01). At 3 months,
      insignificantly higher number of patients recovered completely in LMWH compared
      to UFH group (30 vs. 20). There was no serious side effect needing withdrawal of
      drugs except one was withdrawn from UFH because of heparin-induced thrombosis.
      CONCLUSION:   Low molecular weight heparin resulted in significantly lower
      hospital mortality in CVST compared to UFH.

PMID- 22416903
TI  - Ghrelin: an emerging new anticonvulsant neuropeptide.
AB  - Neuropeptides appear to be of importance when the central nervous system (CNS) is
      challenged, such as during high-frequency firing and pathologic conditions.
      Potential advantages of treatments that target neuropeptide systems in comparison
      to classical neurotransmitter systems and ion channels revolve around the subject
      of efficacy as well as the reduced likelihood of side effects, thus making them
      attractive candidates for the development of new clinical applications for
      various disorders. The number of neuropeptides linked to epilepsy is on the rise,
      reflecting the increased interest of researchers in this domain. Ghrelin has only
      very recently been introduced into the field of epilepsy, and has already led to
      contradictory clinical publications. There is a great paucity with regard to what
      mechanism of action is utilized by ghrelin to inhibit seizures. In this review we
      disclose how we can better understand the mechanism ghrelin uses to prevent
      seizures, which indirectly could give an insight to researchers who are studying
      ghrelin in other fields of research.

PMID- 22416904
TI  - Complexation between pillar[5]arenes and a secondary ammonium salt.
AB  - We demonstrate that n-octylethyl ammonium hexafluorophosphate (G) can thread
      through the cavity of 1,4-dimethoxypillar[5]arene to form a [2]pseudorotaxane
      with a binding constant of 1.09 (+/-0.31) * 10(3) M(-1) in chloroform. The
      formation of this threaded structure has been confirmed by proton NMR
      spectroscopy, electrospray ionization mass spectrometry, and X-ray single crystal
      analysis. The complexation between 1,4-dimethoxypillar[5]arene and G in
      chloroform can be switched off by adding Cl(-). For comparison, the complexation
      between 1,4-bis(n-propoxy)pillar[5]arene and G has also been investigated.

PMID- 22416906
TI  - Evolution of African cassava mosaic virus by recombination between bipartite and
      monopartite begomoviruses.
AB  - BACKGROUND: Cassava mosaic disease (CMD) is a major constraint on cassava
      cultivation in Africa. The disease is endemic and is caused by seven distinct
      cassava mosaic geminiviruses (CMGs), some of them including several variants.
      FINDINGS: From cassava leaf samples presenting CMD symptoms collected in Burkina
      Faso, four DNA-A begomovirus components were cloned and sequenced, showing 99.9%
      nucleotide identity among them. These isolates are most closely related to
      African cassava mosaic virus (ACMV) but share less than 89% nucleotide identity
      (taxonomic threshold) with any previously described begomovirus. A DNA-B genomic
      component, sharing 93% nucleotide identity with DNA-B of ACMV, was also
      characterized. Since all genomic components have a typical genome organization of
      Old World bipartite begomoviruses, this new species was provisionally named
      African cassava mosaic Burkina Faso virus (ACMBFV). Recombination analysis of the
      new virus demonstrated an interspecies recombinant origin, with major parents
      related to West African isolates of ACMV, and minor parents related to Tomato
      leaf curl Cameroon virus and Cotton leaf curl Gezira virus. CONCLUSION: This is
      the first report of an ACMV-like recombinant begomovirus arisen by interspecific
      recombination between bipartite and monopartite African begomoviruses.

PMID- 22416905
TI  - External validity of physical activity interventions for community-dwelling older
      adults with fall risk: a quantitative systematic literature review.
AB  - AIM: To appraise the external validity of physical activity interventions
      designed to reduce falls among community-dwelling older adults, using the reach,
      efficacy/effectiveness, adoption, implementation, and maintenance framework.
      BACKGROUND: Falls are a globally common, important, and a preventable problem.
      The efficacy of physical activity interventions to reduce falls among older
      adults is well established. Translation of this research into practice is slow as
      evidenced by persistently low proportions of older adults who engage in physical
      activities and the rising incidence of falls. DATA SOURCES: Four electronic
      databases were searched for relevant studies published between 2000-2010. Studies
      that examined the effects of physical activity interventions designed to reduce
      falls among community-dwelling older adults were included in this review (n =
      46). DESIGN: This was a quantitative systematic review with narrative synthesis.
      The reach, efficacy/effectiveness, adoption, implementation, and maintenance
      framework guided the identification, appraisal, and synthesis of indicators
      representing study validity. RESULTS: The majority of studies in this review
      described indicators representing internal validity. Details about indicators
      representing external validity were reported infrequently, limiting the
      generalizability of fall-preventive physical activity interventions in diverse
      cultures and social contexts over time. CONCLUSIONS: To foster translational
      research in real world settings, additional programmatic intervention research is
      needed that: (i) targets diverse populations; (ii) incorporates theories of
      behavioural change; (iii) describes and operationalizes critical content that
      enables replication and translation; (iv) tests innovative measures of fall risk
      and physical activity; and (v) evaluates feasibility and acceptability.

PMID- 22416907
TI  - Antiferromagnetic porous metal-organic framework containing mixed-valence
      [Mn(II)4Mn(III)2(MU4-O)2]10+ units with catecholase activity and selective gas
      adsorption.
AB  - A multifunctional porous metal organic framework based on mixed-valence hexa
      nuclear [Mn(III)(2)Mn(II)(4)O(2)(pyz)(2)(C(6)H(5)CH(2)COO)(10)] (pyz = pyrazine)
      units has been synthesized. The complex has been characterized by elemental
      analysis, IR spectroscopy, single-crystal X-ray diffraction analysis, and
      variable-temperature magnetic measurements. The structural analysis reveals that
      the bidentate pyz molecules connect each [Mn(6)] unit to its four [Mn(6)]
      neighbors through the peripheral Mn(II) centers, giving rise to a three
      dimensional (3D) distorted diamond-like porous framework. Variable-temperature (2
      300 K) magnetic susceptibility measurements show the presence of dominant
      antiferromagnetic interactions within the discrete [Mn(6)] cluster that have been
      fitted with a model containing three exchange constants developed for the complex
      (J(1) = -8.6 cm(-1), J(2) = -3.9 cm(-1), and J(3) = -100.0 cm(-1)). Using 3,5-di
      tert-butyl catechol (3,5-DTBC) as the substrate, catecholase activity of the
      complex has been studied; the turn over number is determined to be of 2547 h(-1)
      in acetonitrile. This porous compound shows remarkable selectivity for adsorption
      of CO(2) over N(2) that may be correlated with the effect of window flexibility
      of the pore to the corresponding adsorbate molecules.

PMID- 22416908
TI  - Establishing community partnerships to support late-life anxiety research:
      lessons learned from the Calmer Life project.
AB  - OBJECTIVES: This article outlines the development of the Calmer Life project, a
      partnership established between researchers and faith-based and social service
      organizations to examine the effectiveness of cognitive behavioral therapy (CBT)
      incorporating religious/spiritual components for older African Americans in low
      income communities. METHOD: The program was designed to bypass several barriers
      to delivery of CBT within the specified community; it allows multimodal delivery
      (in person or by telephone) that occurs outside traditional mental health
      settings through faith-based organizations and neighborhood community centers. It
      includes religion/spirituality as an element, dependent upon the preference of
      the participant, and is modular, so that people can select the skills they wish
      to learn. Established relationships within the community were built upon, and
      initial meetings were held in community settings, allowing feedback from
      community organizations. RESULTS: This ongoing program is functioning
      successfully and has strengthened relationships with community partners and
      facilitated increased availability of education and services in the community.
      The lessons learned in establishing these partnerships are outlined. CONCLUSIONS:
      The growth of effectiveness research for late-life anxiety treatments in
      underserved minority populations requires development of functional partnerships
      between academic institutions and community stakeholders, along with treatment
      modifications to effectively address barriers faced by these consumers. The
      Calmer Life project may serve as a model.

PMID- 22416909
TI  - Quantification of lymphedema in a rat model by 3D-active contour segmentation by
      magnetic resonance imaging.
AB  - Secondary lymphedema is a common complication after lymph node excision and
      radiotherapy in cancer therapy. Therapies are limited to symptomatic treatment.
      Adequate animal models to test potential surgical therapies are needed. The aim
      of this study was to induce a tissue environment in the hind leg of the rat
      similar to the one found in operated and irradiated patients. Quantification of
      edematous swelling was performed by an automatic 3D-contour segmentation (ITK-
      Snap (c)) on MR- images. Swelling was induced by excision of superficial inguinal
      and popliteal lymph nodes and adjacent lymphatic vessels, followed by
      radiotherapy of the right groin with a single dose of 15 Gy. Four weeks after
      irradiation, the animals were examined with MRI of both hind legs. Fluid volumes
      around the joint line of the knee were calculated on T2-weighted images. We
      documented a significant higher volume of fluid in the legs following excision of
      lymph nodes and lymphatic vessels, combined with radiotherapy than in control
      legs.

PMID- 22416910
TI  - Yellow nail syndrome: treatment of lymphedema using low pressure compression.
AB  - The present report describes a case with the triad of yellow nail syndrome (YNS)
      and the use of low-pressure compression pump as treatment of lymphedema in YNS. A
      71-year-old woman presented with bilateral lower extremity lymphedema, yellow
      nails, and recurrent bilateral pleural effusion. In this case, we specifically
      focused on lymphedema treatment of the legs besides other recommendations for
      YNS.

PMID- 22416911
TI  - Concentration of indocyanine green does not significantly influence lymphatic
      function as assessed by near-infrared imaging.
AB  - BACKGROUND: Absorbance of near-infrared (600-800 nm) light by the tissue
      components water, melanin, and hemoglobin is minimal. This property allows the
      use of near-infrared-emitting fluorophores for noninvasive, in vivo, real-time
      imaging of tissue, without the interference of autofluorescence experienced with
      imaging in other wavelength ranges. Near-infrared (NIR) fluorescence imaging has
      been used to noninvasively image lymphatic architecture and pumping function in
      animals, as well as in humans. The effects of different doses of a NIR dye,
      indocyanine green (ICG), on lymphatic function have been questioned. This study
      aims to address these concerns in the context of a mouse inguinal-to-axillary
      lymphatic imaging model. METHODS AND RESULTS: We measured lymph propulsive
      velocity and frequency using an imaging system composed of a laser diode for
      excitation of the dye, an image intensifier, and an intensified charge-coupled
      device (ICCD) camera to capture real-time images. At 0.32, 0.645, and 1.3 mM ICG,
      no significant differences in lymphatic propulsive velocity or frequency were
      observed. Additionally, the use of other NIR imaging agents did not result in
      significant differences. CONCLUSIONS: The use of different concentrations of ICG
      and the use of other near-infrared fluorophores for optical imaging of lymphatics
      does not significantly affect lymphatic propulsive velocity or frequency.

PMID- 22416912
TI  - Regional heterogeneity of length-tension relationships in rat lymph vessels.
AB  - BACKGROUND: Heterogeneity of the length-tension relationships in lymph vessels
      has never been evaluated systematically. METHODS AND RESULTS: In this study we
      measured the length-tension relationships in lymph vessels from three different
      regions of the rat: thoracic duct, cervical, and femoral lymph vessels, and
      compared the results to our previous measurements of rat mesenteric lymph
      vessels. We performed isometric force measurements on activated and passive lymph
      vessel segments using a small-vessel wire myograph. We found that all groups of
      vessels had relatively broad plateaus in their active tension versus length
      relationships, suggesting that they are adapted to generate near-maximal tensions
      over a relatively wide range of preloads (at least 0.85-1.05 L(0)). Thoracic duct
      exhibited the flattest active tension curve, particularly for peak active
      tension, in which there was less than a 5% change in peak active tension from
      0.75 to 1.30 of optimal length. Femoral lymph vessels were able to withstand the
      highest estimated pressures, followed by mesenteric and cervical vessels and then
      thoracic duct. CONCLUSIONS: We conclude that lymph vessels effectively adapt
      their contractile force to the particular hydrodynamic conditions (transmural
      pressures and intraluminal flows) that exist in different regions of the
      lymphatic system.

PMID- 22416913
TI  - Poly(2-dimethylamino ethylmethacrylate)-based polymers to camouflage red blood
      cell antigens.
AB  - Poly(2-dimethylamino-ethylmethacrylate) (PDMAEMA) is a cationic polymer when
      dissolved in a 7.4 pH fluid. Owing to its ionic nature, this polycation interacts
      with the negatively charged cell membrane surface of red blood cells (RBCs). The
      electrostatic self-assembly of PDMAEMA on RBCs membrane can be employed for
      inducing the formation of a polymeric shield camouflaging blood group antigens on
      RBCs as a valuable strategy for developing "universal RBCs" for blood
      transfusion. The purpose of this research was to evaluate the camouflaging
      ability of PDMAEMA homopolymers and PDMAEMA-co-poly(ethylene glycol) copolymers
      differing in molecular weight and architecture. Surprisingly, the PDMAEMAs caused
      a partially masking, no masking, and sensitization of the same RBCs population.
      The MW and architecture of the polymers as well as temperature of PDMAEMA-RBCs
      treatment influenced the results observed. Herein, the very particular reactivity
      of PDMAEMAs and RBCs is analyzed and discussed.

PMID- 22416914
TI  - Attentional capture by emotional faces is contingent on attentional control
      settings.
AB  - Attentional capture by schematic emotional faces was investigated in two
      experiments using the flanker task devised by Eriksen and Eriksen (1974). In
      Experiment 1, participants were presented with a central target (a schematic face
      that was either positive or negative) flanked by two identical distractors, one
      on either side (schematic faces that were positive, negative, or neutral). The
      objective was to identify the central target as quickly as possible. The impact
      of the flankers depended on their emotional expression. Consistent with a threat
      advantage hypothesis (negative faces are processed faster and attract more
      processing resources), responses to positive faces were slower when these were
      flanked by (response incompatible) negative faces as compared with positive or
      neutral faces, whereas responses to negative faces were unaffected by the
      identity of the flankers. Experiment 2 was a standard flanker task with letter
      stimuli except that the task-neutral flankers were schematic faces that were
      either positive, negative, or emotionally neutral. In this case, in which faces
      and emotional expressions were to be ignored, performance seemed entirely
      unaffected by the faces. This result suggests that attentional capture by
      emotional faces is contingent on attentional control settings.

PMID- 22416915
TI  - Association of the -14C/G MET and the -765G/C COX-2 gene polymorphisms with the
      risk of chronic rhinosinusitis with nasal polyps in a Polish population.
AB  - Chronic rhinosinusitis with nasal polyps is strongly associated with other
      diseases, including asthma and allergy. The following study tested the
      association of the -765 G/C polymorphism of cyclooxygenase-2 (COX-2) encoding
      gene and the -14C/G polymorphism of protooncogen MET (MET) encoding gene with a
      risk of chronic rhinosinusitis with nasal polyps in a Polish population. One
      hundred ninety-five patients of chronic rhinosinusitis with nasal polyps as well
      as 200 sex-, age-, and ethnicity-matched control subjects without chronic
      sinusitis and nasal polyps were enrolled in this study. Among the group of
      patients, 63 subjects were diagnosed with allergy and 65 subjects with asthma,
      respectively. DNA was isolated from peripheral blood lymphocytes of patients as
      well as controls, and gene polymorphisms were analyzed by restriction fragment
      length polymorphism-polymerase chain reaction (RFLP-PCR). Ten percent of the
      samples have been confirmed by a second method single-strand conformation
      polymorphism (SSCP)-PCR. We reported that the -765 G/C COX-2 (odds ratio [OR]
      7.79; 95% confidence interval [CI] 4.88-12.4, p<0.001) and the -14C/G MET (OR
      2.83; 95% CI 1.74-4.61, p<0.001) were associated with an increased risk of
      chronic rhinosinusitis with nasal polyps among analyzed group of patients.
      Moreover, the group of patients without allergy or asthma indicated the
      association of the -765 C/G (OR 7.25; 95% CI 4.38-12.1, p<0.001 and OR 7.61; 95%
      CI 4.47-12.6, p<0.001) genotype of the COX-2 as wells as the -14C/G (OR 2.47; 95%
      CI 1.46-4.17, p<0.001 and OR 2.59; 95% CI 1.54-4.37, p<0.001) genotype of MET
      with an increased risk of chronic rhinosinusitis with nasal polyps. Finally, it
      was also found that the selected group of patients with allergy or asthma
      indicated a very strong association of the -765 G/C (OR 5.64; 95% CI 2.91-10.9
      and OR 4.74; 95% CI 2.49-9.03, p<0.001, respectively) genotype of the COX-2 with
      an increased risk of chronic rhinosinusitis with nasal polyps. Thus, our results
      suggest that COX-2 and MET gene polymorphisms may have deep impact on the risk of
      rhinosinusitis nasal polyp formation, which may also depend on asthma or allergy.
      Our results showed that the -765 G/C polymorphism of COX-2 gene and the -14C/G
      polymorphism of the MET gene may be associated with the risk of chronic
      rhinosinusitis with nasal polyps in a Polish population.

PMID- 22416916
TI  - The host response to endotoxin-contaminated dermal matrix.
AB  - Biologic scaffold materials composed of extracellular matrix (ECM) have been
      shown to promote the formation of site-specific, functional, host tissue
      following placement in a number of preclinical and clinical studies. Endotoxin
      contamination of biomaterials is thought to result in deleterious immune
      responses that may affect the remodeling outcome when present in significant
      quantities. However, the exact amount of endotoxin contamination within or upon
      an ECM-based biologic scaffold that is required to elicit adverse effects in
      recipients is currently unknown. The present study examined the in vitro and in
      vivo effects of endotoxin contamination within an ECM scaffold derived from
      porcine dermis upon the host immune response and the downstream ability of the
      scaffold material to promote constructive tissue remodeling. Test articles with
      endotoxin values that exceed the current U.S. Food and Drug Administration (FDA)
      limit had similar or decreased immune responses both in vitro and in vivo when
      compared with devices that were below the current FDA limit. Dermal matrices
      spiked with large doses of endotoxin (100 ng/mL), equivalent to 10-20 times the
      FDA limit, elicited a robust immune response in vitro. However, by 35 days
      postimplantation, no difference in tissue remodeling was detected, regardless of
      the amount of endotoxin present within the material. These results suggest that
      current endotoxin standards may fall well below levels that induce an adverse
      acute proinflammatory response and associated long-term deleterious effects upon
      tissue remodeling outcomes.

PMID- 22416917
TI  - Clothing and skin: the burqa as an example.

PMID- 22416918
TI  - Ecological structuring of bacterial and archaeal taxa in surface ocean waters.
AB  - The Global Ocean Sampling (GOS) expedition is currently the largest and
      geographically most comprehensive metagenomic dataset, including samples from the
      Atlantic, Pacific, and Indian Oceans. This study makes use of the wide range of
      environmental conditions and habitats encompassed within the GOS sites in order
      to investigate the ecological structuring of bacterial and archaeal taxon ranks.
      Community structures based on taxonomically classified 16S ribosomal RNA (rRNA)
      gene fragments at phylum, class, order, family, and genus rank levels were
      examined using multivariate statistical analysis, and the results were inspected
      in the context of oceanographic environmental variables and structured habitat
      classifications. At all taxon rank levels, community structures of neritic,
      oceanic, estuarine biomes, as well as other exotic biomes (salt marsh, lake,
      mangrove), were readily distinguishable from each other. A strong structuring of
      the communities with chlorophyll a concentration and a weaker yet significant
      structuring with temperature and salinity were observed. Furthermore, there were
      significant correlations between community structures and habitat classification.
      These results were used for further investigation of one-to-one relationships
      between taxa and environment and provided indications for ecological preferences
      shaped by primary production for both cultured and uncultured bacterial and
      archaeal clades.

PMID- 22416919
TI  - The use of automated sequencing techniques to investigate the sequence
      selectivity of DNA-damaging agents.
AB  - In this review, the use of automated DNA sequencing techniques to determine the
      sequence specificity of compounds that interact with DNA is discussed. The
      sequence specificity of a DNA-damaging agent is an essential element in
      determining the cellular mechanism of action of a drug. A number of DNA-damaging
      compounds are mutagenic, carcinogenic, as well as being widely used as cancer
      chemotherapeutic agents. The distribution of lesions in a sequence of DNA can
      give vital clues in the determination of the precise mechanism of interaction of
      the agent with DNA. The DNA sequence specificity of a number of DNA-damaging
      agents has been delineated using automated DNA sequencing technology, and these
      studies are discussed in this review. The current state-of-the-art methodology
      involves capillary electrophoresis with laser-induced fluorescence detection
      usually on an Applied Biosystems ABI 3730 capillary sequencer. This current
      technique has higher resolution, greater sensitivity, higher precision, more
      rapid separation times, is safer and easier to perform than previous methods. The
      two main methods to determine the DNA sequence selectivity of compounds that
      interact with DNA are described: end labelling and the polymerase stop assay. The
      interaction of the antitumour drug, bleomycin, with DNA is utilized to illustrate
      the recent technological advances.

PMID- 22416920
TI  - The expression kinetics of CD137 in chronic hepatitis C patients treated with
      pegylated-interferon and ribavirin.
AB  - OBJECTIVE: CD137, a member of the tumor necrosis factor receptor family,
      generates co-stimulatory signals leading to T-cell activation and proliferation
      for viral eradication. We examined the expression kinetics of CD137 to validate
      whether it can affect treatment outcomes of chronic hepatitis C (CHC) patients.
      METHODS: The expression of CD137 on peripheral blood mononuclear cells (PBMC)
      from 50 CHC patients and 20 healthy controls was analyzed by flow cytometry.
      CD137 expression levels were examined before treatment, and every 4 weeks during
      treatment until week 24 or 48, and at the 24-week follow-up. RESULTS: CD137
      expression on PBMC was significantly lower in CHC patients than controls (15.5 +/
      7.8% vs 23.4 +/- 5.2%; p < 0.05). Patients with sustained virological response
      (SVR) showed higher level of CD137 expression on PBMC than treatment failures at
      week 4 (20.11% vs 10.97%; p < 0.05) and week 12 (15.48% vs 5.74%; p < 0.01).
      CD137 expression on CD4 T cells was also higher in patients with SVR at week 8
      (7.75% vs 3.29%; p < 0.05). CD137 expression on PBMC from patients with SVR
      recovered to the control level at the 24-week follow-up. In multivariate
      analysis, the increased expression of CD137 at week 4 and genotype non-1 were
      significantly associated with SVR. CONCLUSIONS: The increased expression of CD137
      within 12 weeks after the initiation of interferon therapy might be associated
      with a successful treatment outcome. Modulation to improve expression of CD137
      might improve efficacy of CHC treatment.

PMID- 22416921
TI  - How effective are programs at managing transition from hospital to home? A case
      study of the Australian Transition Care Program.
AB  - BACKGROUND: An increasing demand for acute care services due in part to rising
      proportions of older people and increasing rates of chronic diseases has led to
      new models of post-acute care for older people that offer coordinated discharge,
      ongoing support and often a focus on functional restoration. Overall, review of
      the literature suggests there is considerable uncertainty around the
      effectiveness and resource implications of the various model configurations and
      delivery approaches. In this paper, we review the current evidence on the
      efficacy of such programs, using the Australian Transition Care Program as a case
      study. DISCUSSION: The Australian Transition Care Program was established at the
      interface of the acute and aged care sectors with particular emphasis on
      transitions between acute and community care. The program is intended to enable a
      significant proportion of care recipients to return home, rather than prematurely
      enter residential aged care, optimize their functional capacity, and reduce
      inappropriate extended lengths of hospital stay for older people. Broadly, the
      model is configured and targeted in accordance with programs reported in the
      international literature to be effective. Early evaluations suggest good
      acceptance of the program by hospitals, patients and staff. Ultimately, however,
      the program's place in the array of post-acute services should be determined by
      its demonstrated efficacy relative to other services which cater for similar
      patient groups. SUMMARY: Currently there is a lack of robust evaluation to
      provide convincing evidence of efficacy, either from a patient outcome or cost
      reduction perspective. As the program expands and matures, there will be
      opportunity to scrutinise the systematic effects, with lessons for both
      Australian and international policy makers and clinical leaders.

PMID- 22416922
TI  - Five decades of promotion techniques in cigarette advertising: a longitudinal
      content analysis.
AB  - This study examines frequencies and types of promotion techniques featured in
      five decades of cigarette advertising relative to five major smoking eras.
      Analysis of 1,133 cigarette advertisements collected through multistage sampling
      of 1954 through 2003 issues of three youth-oriented magazines found that 7.6% of
      the analyzed ads featured at least one promotion technique. Across smoking eras
      the proportion of promotion in the ads steadily increased from 1.6% in the "pre
      broadcast ban era" to 10.9% in the "the pre-Master Settlement Agreement (MSA)
      era" and 9% in "post-MSA era." The increased use of sponsorships/events in
      cigarette ads for youth-oriented brands warrants more attention from tobacco
      control experts and government regulators.

PMID- 22416923
TI  - Health care reform through the eyes of patients: a qualitative look at Medicaid
      redesign.
AB  - This research examines consumer choice in Medicaid insurance plans. As part of
      the 2005 Federal Deficit Reduction Act, a number of states have implemented new
      Medicaid programs targeted to a subset of the Medicaid population. These programs
      offer consumers a choice of plans and this research examines consumer choice in
      one state's program. As part of a broader survey, participants were given the
      opportunity to explain, in their own words, why they selected their plan. We
      systematically interpret this qualitative data and then develop a series of
      propositions relating to Medicaid health care plan choice and marketing/public
      policy issues surrounding this choice.

PMID- 22416924
TI  - Impact of celebrity pitch in direct-to-consumer advertising of prescription
      drugs.
AB  - Online surveys were conducted to determine the impact of endorser credibility,
      endorser effectiveness, and consumers' involvement in direct-to-consumer
      advertising. In a randomized posttest only study, using the elaboration
      likelihood model, survey participants (U.S. adults) were either exposed to a
      fictitious prescription drug ad with a celebrity or a noncelebrity endorser.
      There was no significant difference in credibility and effectiveness between the
      celebrity and the noncelebrity endorser. High involvement consumers viewed the ad
      more favorably and exhibited significantly stronger drug inquiry intentions
      during their next doctor visit. Further, consumers' involvement did not moderate
      the effect of celebrity endorser.

PMID- 22416925
TI  - Marketing responsible drinking behavior: comparing the effectiveness of
      responsible drinking messages tailored to three possible "personality"
      conceptualizations.
AB  - We investigated whether a thoroughly personalized message (tailored to a person's
      "Big Five" personality traits) or a message matched to an alternate form of self
      schema (ideal self-schema) would be more influential than a self-schema matched
      message (that has been found to be effective) at marketing responsible drinking.
      We expected the more thoroughly personalized Big Five matched message to be more
      effective than the self-schema matched message. However, neither the Big Five
      message nor the ideal self-schema message was more effective than the actual self
      schema message. Therefore, research examining self-schema matching should be
      pursued rather than more complex Big Five matching.

PMID- 22416926
TI  - Patients' perceptions of physicians: a pilot study of the influence of prime-time
      fictional medical shows.
AB  - Much criticism has fallen onto prime-time crime shows for skewing the perception
      the public has on crime. Could the same criticism apply to prime-time medical
      dramas, which tend to be among the most watched television shows today, for
      skewing patients' expectations? In the past, physicians on prime-time fictional
      medical shows tended to be depicted in a positive manner. However, today's
      medical dramas often portray physicians in a less positive context. The results
      of this study showed that television exposure only negatively affect patients'
      perceptions of physicians in regards to physical attractiveness and character,
      but not to physician propriety, power, communication, sociability, extroversion,
      competence, and composure. In addition, this study showed that prime-time
      fictional shows affect patient-physician interactions.

PMID- 22416927
TI  - Using projective techniques to consider the societal dimension of healthy
      practices: an exploratory study.
AB  - A photo-elicitation and a collage construction technique provide insights into
      citizens of the United Arab Emirates' (UAE) awareness of the negative effects of
      fast-food consumption, the relationship between awareness and UAE fast-food
      consumption, and the discourses used by the UAE when resisting fast-food
      consumption. The study draws on two disciplinary backdrops: risk awareness and
      resistance to behavioral change. The findings show that risk awareness campaigns
      should not solely be linked to bodily concerns but need to develop messages that
      relate to the target audience within its social, political, and economic context.
      What this means conceptually is that health is no longer restricted to the
      individual microlevel dimension but rather emerges from the dialectical interplay
      between taking care of one's self and taking care of one's society.

PMID- 22416928
TI  - Biomarkers vs conventional histological analysis to detect lymph node
      micrometastases in bladder cancer: a real improvement?
AB  - Study Type - Therapy (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? Muscle invasive bladder cancer has a
      mortality rate at 5 years of 50%, despite radical therapy, as a result of tumour
      progression and dissemination. This suggests that half of patients have
      disseminated disease at the time of diagnosis, which is not detected by the
      staging techniques currently used. The prognostic factors (histological grade and
      tumour stage) and current staging techniques do not discriminate between those
      patients who will be cured with surgical treatment and those who will die from
      metastatic spread. New diagnostic and prognostic tools that complement the
      existing methods and provide a proper assessment of carcinoma invading bladder
      muscle are therefore essential. Molecular staging techniques using specific
      biomarkers have been applied in various solid tumours to determine the presence
      of missed tumour cells in lymph nodes (LNs) during routine pathological
      examination. These techniques could identify patients with LN micrometastases who
      may potentially benefit from early treatment with chemotherapy. This study
      compares the performance of conventional histological analysis and molecular
      biomarkers in detecting bladder cancer LN micrometastases and predicting
      patient's clinical outcome. The study found that, even though a clear trend to a
      worse outcome was shown in those patients who became node-positive after
      molecular analysis, no statistical differences were found in cancer-specific and
      recurrence-free survival analysis between those patients who were negative by
      histology but positive by molecular analysis and those who were negative by both
      techniques. We concluded that molecular analysis of LN spreading in bladder
      cancer has a better detection rate than conventional histological examination.
      OBJECTIVE: * To improve the sensitivity of histological examination in detecting
      occult lymph node (LN) dissemination of bladder cancer using gene expression
      analysis. PATIENTS AND METHODS: * We carried out a retrospective study that
      included 504 formalin-fixed paraffin-embedded LNs from 90 patients with muscle
      invasive bladder cancer and 35 controls. * Gene expression values of two
      molecular biomarkers (FXYD3 and KRT20) were analysed using reverse transcription
      real-time quantitative PCR (RT-qPCR). * Molecular results were compared with
      histological status and patients' clinical outcomes. RESULTS: * Of the 90
      patients analysed, 16 were positive and 74 were negative by histological
      analysis. Of these 74, 19 were classified as positive using RT-qPCR. *
      Significant differences in cancer-specific (P= 0.011) and recurrence-free (P=
      0.009) survival were found between the three patient groups (patients positive by
      both techniques, patients negative by both techniques, and patients negative by
      histological but positive by molecular analysis). * A significant difference was
      not found between histologically negative but molecularly positive patients and
      patients who were negative by both techniques, but a clear trend to a worse
      outcome was found in those patients who became node-positive after molecular
      analysis. CONCLUSIONS: * The analysis of FXYD3 and KRT20 could improve current
      pathological examination for the detection of micrometastases in LNs. * Further
      and more extensive studies will determine the real prognostic value of such LN
      micrometastases.

PMID- 22416929
TI  - Enhanced photochemical [6pi] electrocyclization within the lipophilic protein
      binding site.
AB  - Photocyclization of N-methyldiphenylamine to N-methylcarbazole is achieved within
      the microenvironment provided by site I of serum albumins. Quantum yield
      determinations, combined with transient absorption spectroscopic detection of the
      dihydrocarbazole intermediate, demonstrate that protein encapsulation provides a
      subtle control of the kinetic parameters, leading to optimized efficiencies.

PMID- 22416930
TI  - Econometric studies on pharmacist care services are lacking--a call for papers.

PMID- 22416931
TI  - Pharmaceutical care in a community-based practice setting in Jordan: where are we
      now with our attitudes and perceived barriers?
AB  - OBJECTIVES: The objective of this study was to answer the following questions.
      How do community pharmacists in Jordan understand pharmaceutical care? What is
      the extent of pharmaceutical care practice in community pharmacies in Jordan?
      What are the main barriers to practising pharmaceutical care in Jordan? What is
      the attitude of community pharmacies in Jordan when considering provision of
      pharmaceutical care? METHOD: A questionnaire was hand delivered to a random
      sample of 310 community pharmacists. The questionnaire was composed of six
      different sections including patient demographics, pharmacists' understanding of
      pharmaceutical care, frequencies of practice of pharmaceutical care, pharmacists'
      general attitudes about pharmaceutical care, pharmacists' intentions to provide
      specific pharmaceutical care activities and barriers to providing pharmaceutical
      care. Frequencies, percentages, means and standard deviations were used to
      describe pharmacists' responses. Chi-square and regression analysis were also
      conducted to identify important associations. KEY FINDINGS: More than 62% of
      respondents had a correct understanding of the basic concept of pharmaceutical
      care. The data show that the level of reported pharmaceutical care activities was
      limited. In general pharmacists have very good attitudes toward pharmaceutical
      care. Interestingly, more than 90% of respondents fully support the concept of
      pharmaceutical care. The need for pharmaceutical care training was found to be
      the top barrier to the provision of pharmaceutical care as indicated by more than
      80% of pharmacists. CONCLUSIONS: While pharmaceutical care provision is limited
      at this stage in Jordan, the responding pharmacists had a good understanding of
      pharmaceutical care. They expressed a willingness to implement pharmaceutical
      care practice but have identified a number of barriers to successful
      implementation. With the introduction of PharmD and Master of Clinical Pharmacy
      programmes, publication of the results of local studies on the benefit of
      pharmaceutical care, improved communications with physicians and modification of
      the current undergraduate pharmacy curriculum to include more focus on
      therapeutics and pharmaceutical care, many of these perceived barriers may be
      eliminated in the future.

PMID- 22416932
TI  - Interpersonal interactions, job demands and work-related outcomes in pharmacy.
AB  - Objectives  The objective of this study was to examine the interaction between
      job demands of pharmacists and resources in the form of interpersonal
      interactions and its association with work-related outcomes such as
      organizational and professional commitment, job burnout, professional identity
      and job satisfaction. The job demands-resources (JD-R) model served as the
      theoretical framework. Methods  Subjects for the study were drawn from the
      Pharmacy Manpower Project Database (n = 1874). A 14-page mail-in survey measured
      hospital pharmacists' responses on the frequency of occurrence of various job
      related scenarios as well as work-related outcomes. The study design was a 2 * 2
      factorial design. Responses were collected on a Likert scale. Descriptive
      statistics, reliability analyses and correlational and multiple regression
      analyses were conducted using SPSS version 17 (SPSS, Chicago, IL, USA). Key
      findings  The 566 pharmacists (30% response rate) who responded to the survey
      indicated that high-demand/pleasant encounters and low-demand/pleasant encounters
      occurred more frequently in the workplace. The strongest correlations were found
      between high-demand/unpleasant encounters and frequency and intensity of
      emotional exhaustion. Multiple regression analyses indicated that when
      controlling for demographic factors high-demand/unpleasant encounters were
      negatively related to affective organizational commitment and positively related
      to frequency and intensity of emotional exhaustion. Low-demand/pleasant
      encounters were positively related to frequency and intensity of personal
      accomplishment. Low-demand/unpleasant encounters were significantly and
      negatively related to professional commitment, job satisfaction and frequency and
      intensity of emotional exhaustion, while high-demand/pleasant encounters were
      also related to frequency and intensity of emotional exhaustion Conclusion 
      Support was found for the JD-R model and the proposed interaction effects. Study
      results suggest that adequate attention must be paid to the interplay between
      demands on the job and interactions with healthcare professionals to improve the
      quality of the pharmacist's work life. Future research should examine other types
      of job demands and resources.

PMID- 22416933
TI  - Ethnic differences of medicines-taking in older adults: a cross cultural study in
      New Zealand.
AB  - OBJECTIVES: The literature identifies many barriers to medicines use, including
      bio-psycho-social issues, but less is known regarding ethno-cultural barriers,
      which are important in culturally diverse nations. The aim of this study was to
      explore ethnic differences in attitudes to medicines and medicines-taking,
      focusing on the main constituents of the New Zealand (NZ) population: NZ
      European, Maori (the indigenous people of NZ), Pacific and Asian peoples.
      METHODS: A qualitative study involving a series of focus groups was conducted.
      Participants (>50 years old) taking medicines were recruited from various
      community-based groups. The focus group discussions were transcribed verbatim and
      analysed for key themes via manual inductive coding and constant comparison. KEY
      FINDINGS: Twenty focus groups (n=100 participants) were conducted. Three key
      common themes emerged: (1) conception of a medicine; (2) self-management of
      medication; and (3) seeking further medicines information. In general, NZ
      European participants had a very narrow view of what a medicine is, were
      motivated to source medicines information independently and were very proactive
      in medicines management. At the other end of the spectrum, Pacific peoples
      expressed a broad view of what constitutes a medicine, were not motivated to
      source medicines information independently and were not proactive in medicines
      management, tending to instead rely on healthcare professionals for answers. The
      findings from the various ethnic groups highlight differences in attitudes to
      medicines per se and medicines-taking; these influences on medication-taking
      behaviour need to be considered in the provision of pharmaceutical care.
      CONCLUSION: Ethnic differences in attitudes to medicines and medicines-taking are
      apparent, although there are some commonalities in terms of needs regarding
      support and advice around medicines' use. This will help inform the development
      of resources and communication tools to assist pharmacists in providing
      pharmaceutical care to diverse patient populations.

PMID- 22416934
TI  - How to engage experienced medicine users at the counter for a pharmacy-based
      asthma inhaler service.
AB  - OBJECTIVES:   Recent studies have identified recruitment of customers at the
      pharmacy counter as a limiter to successful provision of cognitive services in
      community pharmacies especially that of experienced customers with refill
      prescriptions. The aim of the paper is to gain insight into current problems of
      recruiting. METHODS: A qualitative study was conducted based on semi-structured
      interviews with 12 participants in a project in 2010 aimed at optimising
      recruitment of experienced asthma patients for the Inhaler Technique Assessment
      Service in Denmark. An ad hoc analysis was applied in order to interpret pharmacy
      staff perceptions of experienced asthma patients in comparison with newly
      diagnosed patients and to categorise the types of developed recruitment
      strategies as to whether they reflected a technical or everyday-life perspective
      on medicine. KEY FINDINGS: Effective recruitment processes were found to follow a
      generic pattern which consisted of a special type of opening question followed by
      providing a justification for the service. The participants perceived that the
      main difference between experienced and newly diagnosed patients was their degree
      of knowledge about their condition or correct inhaler technique. Most questions,
      and especially those related to reasons for motivating the customer to accept the
      service, were dominated by a professional technical understanding of medicine. In
      particular, follow-up justification based on a life-world perspective needs to be
      developed further. The identified type of communication might prevent some
      customers from accepting the service as they are not motivated by technical
      arguments but rather by how their daily symptoms can be relieved. CONCLUSIONS:
      Pharmacy staff should focus both on adequate opening questions as well follow-up
      justification when trying to recruit customers for cognitive services. The study
      might inform future studies on how to create new and more adequate strategies for
      recruitment of customers for relevant cognitive services in community pharmacies.

PMID- 22416935
TI  - Evaluation of a multi staged professional development course for practising
      pharmacists in anticoagulation management.
AB  - BACKGROUND: With the evolution of pharmacist prescriptive authority in Alberta,
      Canada, professional development courses need to impact change in daily practice.
      We designed a multi stage course targeting anticoagulation management with
      several components: (1) a print-based course to develop foundational knowledge;
      (2) a 2-day workshop; (3) a 3-day experiential programme; (4) distance mentorship
      to practice site; and (5) two full-day mentorship meetings. OBJECTIVE: To assess
      the impact of a comprehensive anticoagulation professional development course on
      practising pharmacists' knowledge, confidence and daily practice, with
      documentation of resources for the mentorship phases. METHODS: A mixed method of
      evaluation using surveys to assess pharmacist knowledge and confidence and semi
      structured interviews to assess the impact on practice. Surveys were conducted
      prior to and following the workshop, after the experiential training and 4-6
      months following completion of the workshop. Interviews were conducted following
      the experiential training and 4-6 months after the workshop. RESULTS: Enrolment
      for the complete multi stage course was limited to 12 pharmacists, while another
      59 completed the course to the end of the workshop. Pharmacists completing the
      entire course had improved knowledge scores following the workshop, and between
      the workshop and 3-day experiential. These scores declined at 4-6 months.
      Improvements in confidence occurred throughout the course. At the final
      interview, all pharmacists indicated a positive impact on their practice.
      Mentorship was feasible and imperative to offer security to facilitate practice
      change. CONCLUSIONS: Overall, this comprehensive multi stage course improved
      knowledge, confidence and practice for pharmacists.

PMID- 22416936
TI  - How do pharmacy students learn professionalism?
AB  - OBJECTIVE: To understand and clarify how professionalism is learnt, cultivated
      and facilitated in pharmacy education. METHODS: Qualitative methodology involving
      three UK schools of pharmacy was used, including documentary analysis of course
      materials, interviews with seven teaching staff, six focus groups with 38 final
      year pharmacy students and observation of professional pharmacy practice classes.
      We used a 'curriculum mapping' framework; analysis was thematic, with
      triangulation of methods and constant comparison between groups of participants
      and schools. KEY FINDINGS: Students and teachers found defining professionalism
      difficult, but they identified common attitudinal and behavioural attributes.
      These were predominantly based on students' work experience, and role models were
      identified as particularly influential. Professionalism learning needed to be
      grounded and longitudinal throughout the curriculum. Practical classes and the
      use of real-life examples and role plays were influential; and teacher
      practitioners appeared particularly valuable due to their dual base in practice.
      Explicit statements in year books and codes of conduct were valuable, especially
      if they were reinforced and carried through. CONCLUSIONS: This study offers novel
      insights into professionalism learning during undergraduate education in the UK,
      by triangulating evidence from different sources and perspectives. It not only
      underpins the importance of professionalism learning but also highlights
      approaches which appeared valuable within the constraints of an otherwise
      artificial university environment.

PMID- 22416937
TI  - The microbial contamination of pressurised metered-dose inhalers anonymously
      sourced from the South-East Queensland Australia community population.
AB  - OBJECTIVES: To provide preliminary evidence regarding the presence, identity and
      level of microbial contamination of metered-dose inhalers sourced from the
      community. To correlate the level of microbial colonisation to the visible
      presence of debris on the interior and exterior surface of the device mouthpiece.
      METHODS: In this exploratory study, 45 post-use de-identified pressurised metered
      dose inhalers were collected from the South-East Queensland Australian community.
      Prior to swabbing, the presence of visible debris on the internal and external
      surfaces of the mouthpiece was recorded for each device. Swabs taken from
      external and inner surfaces of the mouthpiece of each device were streaked onto
      standard growth media for colony counts. Individual colonies were selected and
      enriched then streaked onto a range of differential and chromogenic media for
      differential identification. KEY FINDINGS: A total of 36 post-use pressurised
      metered dose inhalers (80%) were shown to be colonised by microbes relative to
      unused devices (P=0.01). Devices were primarily colonised by common respiratory
      flora, including Staphylococcus, Streptococcus and Haemophilus species. Of
      greatest concern was the positive identification of methicillin-resistant
      Staphylococcus aureus (18%) and extended-spectrum beta-lactamase-producing
      Enterobacteriaceae (7%), Pseudomonas aerugonisa (2%) and Candida species (9%).
      The level of internal microbial contamination appeared to correlate to the
      presence of visible debris on the inside of the inhaler mouthpiece (P=0.06) but
      not external debris (P=0.59) while external contamination was not associated with
      internal (P=0.99) or external debris (P=0.63). CONCLUSIONS: These preliminary
      data suggest that pressurised metered dose inhalers are potential reservoirs for
      bacteria. While this study was not aimed at determining the impact that
      contaminated pressurised metered-dose inhalers may have on the user, future
      research is being conducted to address the implications of these findings and the
      consequences they may have for the population of users.

PMID- 22416938
TI  - Sustainability of a pharmacist-driven pathway for osteoporosis-related fractures
      on an orthopaedic unit after a 5-year period.
AB  - OBJECTIVES: Diagnosis and management of osteoporosis in hospitals are poor.
      Effective medications for reducing fracture risk are often underutilised in
      hospital settings. Studies have shown that improvements in secondary prevention
      of osteoporosis can occur with the implementation of clinical pathways and are
      effective in improving the prescription for osteoporosis medications. We aimed to
      assess the long-term sustainability of the benefit of the osteoporosis pathway
      implemented at The Queen Elizabeth Hospital, Adelaide, Australia, in 2003.
      METHODS: An audit was performed to review the rate of prescription for
      osteoporosis therapy 5 years after the implementation of a pharmacist-driven
      osteoporosis pathway in patients presented with a minimal trauma fracture and
      admitted to the Department of Orthopaedics at The Queen Elizabeth Hospital. KEY
      FINDINGS: Our review of a 5-year period shows that the rate of prescription for
      osteoporosis therapy in this patient group is 95%. CONCLUSIONS: The pharmacist
      driven osteoporosis pathway at The Queen Elizabeth Hospital has sustained the
      rate of prescription for osteoporosis therapy over a prolonged period of time.

PMID- 22416940
TI  - Stabilization of miniemulsion droplets by cerium oxide nanoparticles: a step
      toward the elaboration of armored composite latexes.
AB  - Stable methyl methacrylate (MMA) miniemulsions were successfully prepared using
      for the first time cerium oxide (CeO(2)) nanoparticles as solid stabilizers in
      the absence of any molecular surfactant. The interaction between MMA droplets and
      CeO(2) nanoparticles was induced by the use of methacrylic acid (MAA) as a
      comonomer. Both MAA and CeO(2) contents played a key role on the diameter and the
      stability of the droplets formed during the emulsification step. Cryo
      transmission electron microscopy (TEM) images of the suspensions formed with 35
      wt % of CeO(2) showed the presence of polydisperse 50-150 nm spherical droplets.
      More surprisingly, some nonspherical (likely discoidal) objects that could be the
      result of the sonication step were also observed. The subsequent polymerization
      of these Pickering miniemulsion droplets led to the formation of composite PMMA
      latex particles armored with CeO(2). In all cases, the conversion was limited to
      ca. 85%, concomitant with a loss of stability of the latex for CeO(2) contents
      lower than 35 wt %. This stability issues were likely related to the screening of
      the cationic charges present on CeO(2) nanoparticles upon polymerization. TEM
      images showed mostly spherical particles with a diameter ranging from 100 to 400
      nm and homogeneously covered with CeO(2). Besides, for particles typically larger
      than 200 nm, a buckled morphology was observed supporting the presence of
      residual monomer at the end of the polymerization and consistent with the limited
      conversion. The versatility of these systems was further demonstrated using 35 wt
      % of CeO(2) and replacing MMA by n-butyl acrylate (BA) either alone or in
      combination with MMA. Stable monomer emulsions were always obtained, with the
      droplet size increasing with the hydrophobicity of the oil phase, pointing out
      the key influence of the wettability of the solid stabilizer. The polymerization
      of Pickering miniemulsion stabilized by CeO(2) nanoparticles proved to be an
      efficient strategy to form armored composite latex particles which may find
      applications in coating technology.

PMID- 22416939
TI  - Forced expiratory volume is associated with cardiovascular and cortisol reactions
      to acute psychological stress.
AB  - It has been argued that blunted cardiovascular and cortisol reactions to acute
      psychological stress reflect a dysregulation of the neural system that supports
      motivation. We examined the association between forced expiratory volume in 1 s,
      an effort (hence motivation) dependent measure of lung function measured by
      spirometry, and cardiovascular and cortisol reactions to a battery of standard
      psychological stress tasks, assessed 7 years later. Irrespective of how it was
      expressed, low forced expiratory volume was associated with blunted heart rate
      and cortisol stress reactivity. The association survived adjustment for smoking,
      a range of anthropometric and sociodemographic covariates, and commitment to the
      stress tasks, as well as cognitive ability.

PMID- 22416941
TI  - Gastrointestinal health and function in weaned pigs: a review of feeding
      strategies to control post-weaning diarrhoea without using in-feed antimicrobial
      compounds.
AB  - For the last several decades, antimicrobial compounds have been used to promote
      piglet growth at weaning through the prevention of subclinical and clinical
      disease. There are, however, increasing concerns in relation to the development
      of antibiotic-resistant bacterial strains and the potential of these and
      associated resistance genes to impact on human health. As a consequence, European
      Union (EU) banned the use of antibiotics as growth promoters in swine and
      livestock production on 1 January 2006. Furthermore, minerals such as zinc (Zn)
      and copper (Cu) are not feasible alternatives/replacements to antibiotics because
      their excretion is a possible threat to the environment. Consequently, there is a
      need to develop feeding programs to serve as a means for controlling problems
      associated with the weaning transition without using antimicrobial compounds.
      This review, therefore, is focused on some of nutritional strategies that are
      known to improve structure and function of gastrointestinal tract and (or)
      promote post-weaning growth with special emphasis on probiotics, prebiotics,
      organic acids, trace minerals and dietary protein source and level.

PMID- 22416943
TI  - Preclinical antiepileptic actions of selective serotonin reuptake inhibitors-
      implications for clinical trial design.
AB  - Selective serotonin reuptake inhibitors (SSRIs) can reduce seizure frequency in
      humans, but no large-scale clinical trials have been done to test the utility of
      SSRIs as potential antiepileptic drugs. This may be caused in part by a small
      number of reports on seizures triggered by SSRI treatment. The preclinical
      literature on SSRIs is somewhat conflicting, which is likely to contribute to the
      hesitance in accepting SSRIs as possible anticonvulsant drug therapy. A careful
      review of preclinical studies reveals that SSRIs appear to have region-specific
      and seizure subtype-specific effects, with models of chronic partial epilepsy
      being more likely to respond than models of acute generalized seizures. Moreover,
      this preclinical profile is similar to that of clinical antiepileptic drugs.
      These observations suggest that SSRIs are promising antiepileptic agents, and
      that clinical trials may benefit from defining patient groups according to the
      underlying pathology.

PMID- 22416942
TI  - Patterns and influencing factor of synonymous codon usage in porcine circovirus.
AB  - BACKGROUND: Analysis of codon usage can reveal much about the molecular evolution
      of the viruses. Nevertheless, little information about synonymous codon usage
      pattern of porcine circovirus (PCV) genome in the process of its evolution is
      available. In this study, to give a new understanding on the evolutionary
      characteristics of PCV and the effects of natural selection from its host on the
      codon usage pattern of the virus, Patterns and the key determinants of codon
      usage in PCV were examined. METHODS: We carried out comprehensive analysis on
      codon usage pattern in the PCV genome, by calculating relative synonymous codon
      usage (RSCU), effective number of codons (ENC), dinucleotides and nucleic acid
      content of the PCV genome. RESULTS: PCV genomes have relatively much lower
      content of GC and codon preference, this result shows that nucleotide constraints
      have a major impact on its synonymous codon usage. The results of the
      correspondence analysis indicate codon usage patterns of PCV of various
      genotypes, various subgenotypes changed greatly, and significant differences in
      codon usage patterns of Each virus of Circoviridae.There is much comparability
      between PCV and its host in their synonymous codon usage, suggesting that the
      natural selection pressure from the host factor also affect the codon usage
      patterns of PCV. In particular, PCV genotype II is in synonymous codon usage more
      similar to pig than to PCV genotype I, which may be one of the most important
      molecular mechanisms of PCV genotype II to cause disease. The calculations
      results of the relative abundance of dinucleotides indicate that the composition
      of dinucleotides also plays a key role in the variation found in synonymous codon
      usage in PCV. Furthermore, geographic factors, the general average hydrophobicity
      and the aromaticity may be related to the formation of codon usage patterns of
      PCV. CONCLUSION: The results of these studies suggest that synonymous codon usage
      pattern of PCV genome are the result of interaction between mutation pressure and
      natural selection from its host. The information from this study may not only
      have theoretical value in understanding the characteristics of synonymous codon
      usage in PCV genomes, but also have significant value for the molecular evolution
      of PCV.

PMID- 22416944
TI  - The experiences of medically fragile adolescents who require respiratory
      assistance.
AB  - AIMS: To report a study of the experiences of medically fragile adolescents who
      require respiratory assistance. BACKGROUND: The population of medically fragile
      adolescents has grown in recent decades because of the sequelae of prematurity,
      injuries and chronic or terminal illnesses. Medically fragile adolescents who
      require respiratory assistance are part of this unique population, yet as nurses,
      we know little about their experiences and the best approaches to use in caring
      for them. DESIGN: A qualitative design, interpretive phenomenology was used in
      this study. METHODS: Interpretive phenomenology was used to describe and
      interpret the experience of 11 medically fragile adolescents (ages 13-18 years
      old) who required respiratory assistances of tracheostomies, ventilator support
      and Bi-level positive airway pressure. Between April 2010-September 2010,
      audiotaped semi-structured interviews were conducted with the adolescents. Data
      analysis was completed using a stepped approach to identify themes. FINDINGS:
      Five themes were identified from the interviews with the adolescents: 'Get to
      know me', 'Allow me to be myself', 'Being there for me', 'No matter what,
      technology helps' and 'I am an independent person'. CONCLUSIONS: Medically
      fragile adolescents have a clear view of who they are as a person. They want
      nurses to view them as a person, not just a patient. The adolescents said that
      friends were there for them when they needed support. Technology had meanings
      that enhanced daily living and existed as a part of their day, not their whole
      day. The adolescents were actively engaging in activities and strategies to
      achieve their goals of independence.

PMID- 22416945
TI  - Beliefs about Alzheimer's disease in Britain.
AB  - OBJECTIVES: Alzheimer's disease (AD) represents one of the most debilitating
      conditions affecting the elderly. Despite the prevalence and consequences of AD,
      surveys have revealed that the general public in North America and Australia hold
      numerous misconceptions of the disease. The aim of this study was to examine
      whether misconceptions of AD are also endorsed by adults in Britain. METHOD: The
      Alzheimer's disease knowledge scale (ADKS) was completed by 312 adults residing
      in Lincolnshire, UK. The ADKS contains 30 true or false statements pertaining to
      risk factors, assessment and diagnosis, symptoms, course, life impact,
      caregiving, and treatment and management of AD. RESULTS: Regardless of age,
      education, and familiarity with AD, respondents in this survey demonstrated a
      good understanding (>=80% mean correct) of some items from all categories.
      However, knowledge gaps exist about the course of the disease, and of conditions
      that can exacerbate (inadequate nutrition) or simulate (depression) the symptoms
      of AD. Moreover, a large proportion of respondents (~75%) are unaware that
      hypertension or hypercholesterolemia may increase ones predisposition to
      developing AD. CONCLUSION: Respondents revealed knowledge gaps pertaining to
      conditions that masquerade as AD, increase ones vulnerability to AD, and
      exacerbate AD symtomatology. Educational campaigns that specifically target these
      issues may help reduce the impact of AD.

PMID- 22416946
TI  - Bladder diverticulum: clinicopathologic spectrum in pediatric patients.
AB  - Urinary bladder diverticula are a relatively rare finding in both the adult and
      pediatric population. Their presence in the adult population has long been
      associated with the development of urothelial carcinoma within the lesion. Our
      goal is to analyze a relatively large pediatric patient population with urinary
      bladder diverticula to expand the body of knowledge on the associated clinical
      symptomatology, congenital syndromes associated with the entity, and treatment
      methods and to further investigate if there is any reason to suspect malignant
      transformation within the pediatric population. A search for pediatric patients
      (0-19 years of age) from 1990 to 2011 revealed 47 patients with 60 diverticula
      within the specified age range. Clinical records and histologic slides for all
      cases were pulled for review, and statistical analysis was performed on the
      results. The most common findings were vesicoureteral reflux (68%), recurrent
      urinary tract infection (55%), and hydronephrosis (40%). Fourteen of 47 (30%)
      patients had an associated congenital syndrome/malformation. Diverticular size
      range was 0.5-10 cm with a mean of 2.56 cm. No patient was found to have overt
      malignancy or dysplastic changes within the diverticula or bladder at the time of
      pathologic evaluation. High association with recognizable clinical symptoms and
      additional urinary tract abnormalities leads to early identification and
      treatment. A sizable percentage of those found to have bladder diverticula within
      the pediatric population will have a congenital syndrome. No association with
      malignancy is seen within pediatric bladder diverticula; it is an extremely
      unlikely event in these young patients.

PMID- 22416947
TI  - The phenomenon of 'chronic Lyme'; an observational study.
AB  - PURPOSES: To chart clinical, laboratory, and psychometric profiles in patients
      who attribute their complaints to chronic Lyme disease. METHODS: We assessed the
      patients by clinical examination, laboratory tests, and questionnaires measuring
      fatigue, depression, anxiety, health-related quality of life, hypochondriasis,
      and illness perceptions. RESULTS: We found no evidence of ongoing Borrelia
      burgdorferi (Bb) infection in any of the 29 included patients using current
      diagnostic guidelines and an extended array of tests. Eight (28%) had other well
      defined illnesses. Twenty-one (72%) had symptoms of unknown cause, of those six
      met the suggested criteria for post-Lyme disease syndrome. Fourteen (48%) had
      presence of anti-Bb antibodies. The patients had more fatigue and poorer health
      related quality of life as compared to normative data, but were not more
      depressed, anxious, or hypochondriacal. Their beliefs about the illness were
      characterized by negative expectations. CONCLUSION: Our patients, who all
      attributed their symptoms to chronic Lyme disease, were heterogeneous. None had
      evidences of persistent Bb infection, but whether current diagnostic criteria are
      functional in patients with longstanding complaints is controversial. Other well
      defined illnesses or sequelae from earlier Lyme disease were probable as main
      explanatory factor in some cases. The patients were not more depressed, anxious,
      or hypochondriacal than the normal population, but they had poorer health-related
      quality of life, more fatigue, and negative expectations about their illness.

PMID- 22416948
TI  - Sequence specific association of tryptic peptides with multiwalled carbon
      nanotubes: effect of localization of hydrophobic residues.
AB  - A model-free approach has been used to study the association of peptides onto
      multiwalled carbon nanotubes (MWCNT) in aqueous solution at ambient pH to
      understand the molecular basis of interaction of the peptides with MWCNT. The
      peptides obtained by tryptic digestion of cytochrome P450cam from  P. putida 
      were allowed to interact with MWCNT, and several peptides were found to bind to
      the nanotube leading to formation of stable homogeneous dispersion of the bionano
      conjugates of MWCNT. The peptides bound to the MWCNT were separated from the
      unbound peptides and sequence analyses by tandem MS/MS technique identified the
      strongly bound peptides as well as the unbound and the weakly bound peptides. The
      peptide-MWCNT conjugate was further characterized by TEM as well as Raman, FTIR,
      vis-NIR absorption, and circular dichroism spectroscopy. A model based on the
      hydrophobicity of residues in the peptides suggested that the amphiphilic
      peptides with localized hydrophobic residues at the center or at one end of the
      sequence form stable dispersions of the peptide-MWCNT conjugates.

PMID- 22416949
TI  - Hydrogen in La2MgNi9D13: the role of magnesium.
AB  - Reversible hydrogen storage capacity of the La(3-x)Mg(x)Ni(9) alloys, charged by
      gaseous hydrogen or by electrochemical methods, reaches its maximum at
      composition La(2)MgNi(9). As (La,Mg)Ni(3-3.5) alloys are the materials used in
      advanced metal hydride electrodes in Ni-MH batteries, this raises interest in the
      study of the structure-properties interrelation in the system La(2)MgNi(9)-H(2)
      (D(2)). In the present work, this system has been investigated by use of in situ
      synchrotron X-ray and neutron powder diffraction in H(2)/D(2) gas and by
      performing pressure-composition-temperature measurements. The saturated
      La(2)MgNi(9)D(13.1) hydride forms via an isotropic expansion and crystallizes
      with a trigonal unit cell (space group R3m (No.166); a = 5.4151(1) A; c =
      26.584(2) A; V = 675.10(6) A(3)). The studied hybrid structure is composed of a
      stacking of two layers resembling existing intermetallic compounds LaNi(5)
      (CaCu(5) type) and LaMgNi(4) (Laves type). These are occupied by D to form
      LaNi(5)D(5.2) and LaMgNi(4)D(7.9). The LaNi(5)D(5.2) slab has a typical structure
      observed for all reported LaNi(5)-containing hybrid structures of the AB(5) +
      Laves phase types. However, the Laves type slab LaMgNi(4)D(7.9) is different from
      the characterized individual LaMgNi(4)D(4.85) hydride. This results from the
      filling of a greater variety of interstitial sites in the
      La(2)MgNi(9)D(13)/LaMgNi(4)D(7.9), including MgNi(2), Ni(4), (La/Mg)(2)Ni(2), and
      (La/Mg)Ni(3), in contrast with individual LaMgNi(4)D(4.85) where only
      La(2)MgNi(2) and Ni(4) interstitials are occupied. Despite a random distribution
      of La and Mg in the structure, a local hydrogen ordering takes place with H atoms
      favoring occupation of two Mg-surrounded sites, triangles MgNi(2) and tetrahedra
      LaMgNi(2). A directional bonding between Ni, Mg, and hydrogen is observed and is
      manifested by a formation of the NiH(4) tetrahedra and MgH(6) octahedra, which
      are connected to each other by sharing H vertexes to form a spatial framework.

PMID- 22416950
TI  - Mercury in bay bolete (Xerocomus badius): bioconcentration by fungus and
      assessment of element intake by humans eating fruiting bodies.
AB  - Concentrations of mercury (Hg) were determined in 221 specimens of bay bolete and
      in 221 samples of corresponding forest topsoil layer (0-10 cm) collected from 18
      sites across geographically and industrially diverse regions of Poland in 2000
      2008. Mercury concentrations in caps and stipes of bay bolete were strongly
      correlated (p < 0.0001), whereas the relationship between the Hg concentrations
      in soil and mushrooms varied depending on the sampling location. The bay bolete
      showed a lower bioconcentration potential of Hg at sites with elevated soil Hg
      concentrations and a higher bioconcentration at sites with lower Hg
      concentrations in soil. In view of Hg content, the consumption of bay boletes
      (caps or whole mushrooms) at the regions surveyed at least at a rate up to 2.5 kg
      per capita weekly in a mushrooming season is safe and will not result in
      exceeding of currently allowable Hg intake doses.

PMID- 22416951
TI  - Adaptive ability, behavior and quality of life pre and posttraumatic brain injury
      in childhood.
AB  - CONTEXT: Traumatic brain injury (TBI) is a common, acquired childhood disability,
      which has been shown to have a significant impact on children's cognitive and
      educational function. While behavioral problems are also noted, there is ongoing
      debate about the contribution of preinjury factors in this domain. Few studies
      have attempted to measure the impact of these preinjury functions on postinjury
      behavior. OBJECTIVE: To compare pre and postinjury adaptive ability, behavior,
      executive function and quality of life (QOL) and to identify factors that
      contribute to outcomes in these domains including injury severity, socio
      demographic and preinjury characteristics. DESIGN: Consecutive recruitments to a
      prospective, longitudinal study, utilizing a between factor design, with injury
      severity as the independent variable. PARTICIPANTS AND METHODS: Children admitted
      to hospital with a diagnosis of TBI aged between 6 and 14 years (n = 205) were
      divided according to injury severity (mild, moderate and severe). Adaptive
      behavior (Vineland Adaptive Behavior Scales), child behavior (Child Behavior
      Checklist), everyday executive functions (Behavior Rating Inventory of Executive
      Function) and QOL (Child Health Questionnaire) assessed at 6 months post-TBI.
      RESULTS AND CONCLUSIONS: Severity by time interactions were identified across a
      range of outcome domains demonstrating that more severe injury is associated with
      a decrease in functional ability at 6 months post-TBI. This effect was most
      pronounced for everyday executive skills, social function and internalizing
      aspects of child behavior. Preinjury function was a consistent predictor of
      postinjury status. Injury severity contributed little to the prediction of
      functional outcomes once preinjury functioning was accounted for in the model.
      Age at injury and family cohesion were relevant to specific outcome domains only.
      Socio-economic status did not contribute significantly to outcome at 6 months.
      Preinjury functioning as reported by parents in the acute phase may be a useful
      predictive tool for identifying children who may be at risk of functioning
      difficulties 6 months post-TBI.

PMID- 22416952
TI  - Molecular modeling of T. rangeli, T. brucei gambiense, and T. evansi sialidases
      in complex with the DANA inhibitor.
AB  - Trypanosomal (trans-) sialidases are enzymes that catalyze the transfer of sialic
      acid residues between host and parasite glycoconjugates. Herein, we have used
      homology modeling to construct the 3D structures of sialidases from Trypanosoma
      brucei and Trypanosoma evansi. Hybrid quantum mechanical/molecular mechanical
      molecular dynamics simulations were used to determine the interaction energy
      between the 2-deoxy-2,3-didehydro-N-acetylneuraminic acid inhibitor and the three
      sialidases studied here. Our results suggest that the two constructed enzymes
      share the same basic fold motive of the Trypanosoma rangeli crystallographic
      structure. In addition, quantum mechanical/molecular mechanical molecular
      dynamics simulations show that the 2-deoxy-2,3-didehydro-N-acetylneuraminic acid
      inhibitor forms a stronger complex with Trypanosoma rangeli than with Trypanosoma
      brucei and Trypanosoma evansi sialidases. Finally, the interaction energy by
      residues shows that the arginine triad plays a decisive role to complex 2-deoxy
      2,3-didehydro-N-acetylneuraminic acid with the enzyme through hydrogen bonding.

PMID- 22416953
TI  - Measuring spirituality as a universal human experience: development of the
      Spiritual Attitude and Involvement List (SAIL).
AB  - Many cancer patients experience spirituality as highly supportive while coping
      with their disease. Most research as well as most questionnaires in this field is
      religious orientated. The Spiritual Attitude and Involvement List was developed
      to enable research on spirituality among religious and nonreligious people. It
      consists of seven subscales that measure connectedness with oneself, with others
      and nature, and with the transcendent. Among a student, a healthy population, a
      healthy interested, a curative cancer, and a palliative cancer sample factorial,
      convergent and discriminant validity were demonstrated, as well as adequate
      internal consistency and test-retest reliability.

PMID- 22416954
TI  - Psychosocial concerns of young African American breast cancer survivors.
AB  - Thirty-three African American breast cancer survivors age 45 or younger
      participated in semistructured phone interviews about psychosocial concerns.
      Twenty-six percent believed treatment interfered with employment. One third
      wanted additional emotional support at and after diagnosis. One half felt cancer
      negatively influenced romantic relationships. Forty-five percent wanted children
      at diagnosis, but one half these women never received fertility information. One
      third reported sexual problems, but 73% never discussed sexuality with providers.
      Fifty-two percent lacked information about cancer-related sexual dysfunction. The
      strength and spirituality of African American women may facilitate cancer
      adjustment, but cultural taboos surrounding women's health issues may interfere
      with successful coping.

PMID- 22416955
TI  - Do patient-reported androgen-deprivation therapy side effects predict anxiety and
      depression among prostate cancer patients undergoing radiotherapy? Implications
      for psychosocial therapy interventions.
AB  - Antiandrogen therapy (AAT) is a common adjunct treatment for prostate cancer
      (PCa) patients and has shown significant benefits to long-term outcomes from
      radiation or surgery. Although AAT has some adverse side effects and data from
      breast cancer patients indicate that such side effects from hormonal therapies
      may contribute to anxiety and depression and may also hinder AAT treatment
      compliance, this issue has not been investigated within a sample of PCa patients.
      This study explores the incidence of AAT side effects in a sample of PCa
      patients, the links between those side effects and anxiety and depression, the
      possible ways in which these factors may contribute to AAT treatment
      noncompliance in PCa patients, and how psychosocial treatments might be developed
      to attend to this issue. 147 PCa patients completed questionnaires on demographic
      factors, treatment compliance, AAT side effects, anxiety and depression. About
      18% of the sample reported AAT side effects, and there was a significant
      association between the presence of side effects and elevated anxiety and
      depression scores. Increased frequency of side effects was significantly
      associated with elevated anxiety, but not depression. The most powerful
      relationship between AAT side effects and anxiety-depression was for the
      subfactors of (1) Fatigue, Pain and Discomfort, and (2) Psychological Agitation
      and Pessimism. Although fatigue, pain, and discomfort may be outcomes of the
      hormonal treatment itself, psychological agitation and pessimism represent a
      discrete psychological pathway between AAT side effects and anxiety and
      depression and (potentially) treatment noncompliance. Methods of addressing
      patients' loss of optimism in their treatment outcomes are discussed.

PMID- 22416956
TI  - Survivorship care planning in colorectal cancer: feedback from survivors &
      providers.
AB  - The Institute of Medicine recommended that all patients receive survivorship care
      plans (SCPs) post-treatment to improve quality of follow-up care. However, little
      is known regarding how survivors utilize SCPs and the congruency between
      providers' and survivors' perspectives. Feedback from colorectal cancer survivors
      (in receipt of a personalized/individualized SCP) and oncology providers was
      obtained via interviews. Survivors noted SCPs benefits of reduced duplicative
      procedures and cancer worry with the synthesized treatment information. Providers
      noted billing/reimbursement and time investiture (for form completion) as
      potential barriers. Further investigation of SCPs is warranted regarding utility
      prior to widespread adoption in follow-up care.

PMID- 22416957
TI  - Caring for a loved one with cancer: it is my job.
AB  - This study investigated the experiences of caregivers of loved ones with cancer
      in Lome, Togo. The authors developed a framework that captures the experiences of
      17 caregivers. The framework explains the exploratory factors that influenced the
      lives of caregivers from the caregivers' own perspectives. Findings showed that
      even though the caregivers experienced significant challenges that affected their
      lives and the lives of their families, because of cultural norms and
      expectations, they tried their best to overcome the challenges. Although some
      reported positive impacts on their family functioning, others reported negative
      impacts such as fragmentation of the family unit. Implications for practice and
      policy are discussed.

PMID- 22416958
TI  - Routine monitoring of quality of life for patients with breast cancer: an
      acceptability and field test.
AB  - As part of the development of a quality of life monitor for women with breast
      cancer, a qualitative acceptability test was conducted among 10 patients, to
      assess their suggestions for improvement. Next, a field test was conducted among
      50 women with breast cancer receiving radiotherapy, chemotherapy, or both
      treatments to examine the use of the monitor in daily practice and to assess
      physicians' and patients' experiences with the monitor. Although patients in
      general held a positive attitude toward the monitor and compliance was high,
      patients regularly were unsure about how the quality of life information was used
      by physicians.

PMID- 22416959
TI  - "You're too young for this": adolescent and young adults' perspectives on cancer
      survivorship.
AB  - Adolescent and young adult cancer survivors face unique challenges not
      systematically addressed by cancer clinicians. Four focus groups and two
      individual interviews were conducted with 19 survivors to profile experiences and
      identify key concerns for future interventions. The resultant themes reflect
      cancer care continuum challenges (such as delays in diagnosis, problems with
      adherence), psychosocial concerns (such as infertility and reproductive concerns,
      changing social relationships, financial burden), and the paradox of being
      diagnosed with cancer as a young adult. Future intervention development for
      adolescent and young adult survivors should involve patient voices at each stage
      of the research process.

PMID- 22416960
TI  - Expression of carbonic anhydrases I/II and the correlation to clinical aspects of
      oral squamous cell carcinoma analyzed using tissue microarray.
AB  - BACKGROUND: Carbonic anhydrases (CA), a family of metalloenzymes, play an
      important role in catalyzing the equilibration of carbon dioxide (CO(2)) and
      carbonic acid (H(2)CO(3)). The role of CAs in tumorigenesis is controversial,
      especially regarding the expression of CA isoenzymes between various tumor types.
      This study explores the correlation between the expressions of CA I and CA II and
      the characteristic features of oral cancer. METHODS: We immunohistochemically
      examined the expressions of CA I and CA II in 279 cases of oral squamous cell
      carcinoma (OSCC) using tissue microarrays. Additionally, the oral cancer cell
      line SCC-9 was used to confirm the relationship between CA I and CA II expression
      and cell growth. RESULTS: We found a significant correlation between positive CA
      I and CA II stains and OSCC for more advanced clinical stage (P = 0.014 or 0.012)
      and larger tumor size (P = 0.008 or 0.038), but not for positive lymph node
      metastasis, distal metastasis, and recurrence. In vitro analysis also showed that
      treatment with a CA inhibitor, acetazolamide, inhibited the growth of SCC-9
      cells. CONCLUSION: We conclude that expressions of CA I and CA II in OSCC samples
      can be used to predict local tumor growth in OSCC patients.

PMID- 22416961
TI  - Microbial CO2 fixation potential in a tar-oil-contaminated porous aquifer.
AB  - CO(2)  fixation is one of the most important processes on the Earth's surface,
      but our current understanding of the occurrence and importance of
      chemolithoautotrophy in the terrestrial subsurface is poor. Groundwater
      ecosystems, especially at organically polluted sites, have all the requirements
      for autotrophic growth processes, and CO(2)  fixation is thus suggested to
      contribute significantly to carbon flux in these environments. We explored the
      potential for autotrophic CO(2)  fixation in microbial communities of a petroleum
      hydrocarbon-contaminated aquifer by detection of functional marker genes (cbbL,
      cbbM), encoding different forms of the key enzyme RubisCO of the Calvin-Benson
      Bassham cycle. Quantification of (red-like) cbbL genes revealed highest numbers
      at the upper fringe of the contaminant plume and the capillary fringe where
      reduced sulphur and iron species are regularly oxidized in the course of
      groundwater table changes. Functional gene sequences retrieved from this area
      were most closely related to sequences of different thiobacilli. Moreover,
      several cultures could be enriched from fresh aquifer material, all of which are
      able to grow under chemolithoautotrophic conditions. A novel, nitrate-reducing,
      thiosulfate-oxidizing bacterial strain, recently described as Thiobacillus
      thiophilus D24TN(T)  sp. nov., was shown to carry and transcribe RubisCO large
      subunit genes of form I and II. Enzyme tests proved the actual activity of
      RubisCO in this strain.

PMID- 22416962
TI  - Causes of diminished renal function in the affected kidney after partial
      nephrectomy.
AB  - OBJECTIVE: To determine the cause of diminished renal function in the affected
      kidney after partial nephrectomy (PN) for renal tumour, we analyzed the
      relationship between operative data and postoperative recovery with respect to
      renal function. PATIENTS AND METHODS: From May 2005 to December 2010, pre- and
      postoperative (1 week and 3 months after the procedure) renal function was
      evaluated by 99mTc- mercaptoacetyltriglycine clearance in 51 patients treated
      with open partial nephrectomy (OPN; n = 24) and laparoscopic partial nephrectomy
      (LPN; n = 27). LPN was performed via retroperitoneal (RPLPN; n = 14) or
      transperitoneal (TPLPN; n = 13) routes. Renal cooling was performed after renal
      hilar clamping in OPN and RPLPN, although not in TPLPN. RESULTS: There were 10
      patients (two in OPN, six in TPLPN, two in RPLPN) who had diminished renal
      function in the affected kidney from 1 week to 3 months after PN. Warm ischaemia
      (versus cold ischaemia; P = 0.017) during renal hilar clamping resulted in
      diminished renal function. Using multivariate analysis, renal cooling influenced
      postoperative diminished renal function (P = 0.008). CONCLUSIONS: Successful
      preservation of renal function after PN depends on renal cooling during renal
      hilar clamping. Cold ischaemia for avoiding renal damage is recommended if renal
      hilar clamping is necessary for tumour extraction.

PMID- 22416963
TI  - Cloning, expression and purification of orthologous membrane proteins: a general
      protocol for preparation of the histidine sensor kinase ETR1 from different
      species.
AB  - Orthologous proteins do not necessarily share the same function in all species
      and those sharing the same function might employ a modified catalytic mechanism.
      Thus, comparative analysis of homologous or orthologous proteins from different
      organisms can provide detailed information on the function and the mechanism of
      an entire protein family. The sensor kinase ETR1 from Arabidopsis thaliana has
      been well characterized by genetic, physiological and biochemical studies.
      However, as further model plants are coming into focus for plant hormone
      research, a general protocol for isolation and purification of orthologous ETR1
      proteins seems instrumental for a detailed molecular analysis of this protein
      family. In this study, we describe the native purification of recombinant ETR1
      from Arabidopsis thaliana by mild solubilization with the zwitter-ionic detergent
      Fos-Choline-14 and single-step purification by immobilized metal ion affinity
      chromatography. The same protocol was successfully applied for the purification
      of the orthologous proteins from the moss Physcomitrella patens subsp. patens and
      the tomato Lycopersicon esculentum. The successful transfer of the purification
      protocol to proteins of the same family which share sequence identity of 63-80%
      only suggests that this protocol presents a general purification strategy which
      is likely to apply also to the purification of other members of the sensor
      histidine kinase family.

PMID- 22416964
TI  - Hydrophobic residues in small ankyrin 1 participate in binding to obscurin.
AB  - Abstract Small ankyrin-1 is a splice variant of the ANK1 gene that binds to
      obscurin A. Previous studies have identified electrostatic interactions that
      contribute to this interaction. In addition, molecular dynamics (MD) simulations
      predict four hydrophobic residues in a 'hot spot' on the surface of the ankyrin
      like repeats of sAnk1, near the charged residues involved in binding. We used
      site-directed mutagenesis, blot overlays and surface plasmon resonance assays to
      study the contribution of the hydrophobic residues, V70, F71, I102 and I103, to
      two different 30-mers of obscurin that bind sAnk1, Obsc6316-6345 and Obsc6231
      6260. Alanine mutations of each of the hydrophobic residues disrupted binding to
      the high affinity binding site, Obsc6316-6345. In contrast, V70A and I102A
      mutations had no effect on binding to the lower affinity site, Obsc6231-6260.
      Alanine mutagenesis of the five hydrophobic residues present in Obsc6316-6345
      showed that V6328, I6332, and V6334 were critical to sAnk1 binding. Individual
      alanine mutants of the six hydrophobic residues of Obsc6231-6260 had no effect on
      binding to sAnk1, although a triple alanine mutant of residues V6233/I6234/I6235
      decreased binding. We also examined a model of the Obsc6316-6345-sAnk1 complex in
      MD simulations and found I102 of sAnk1 to be within 2.2A of V6334 of Obsc6316
      6345. In contrast to the I102A mutation, mutating I102 of sAnk1 to other
      hydrophobic amino acids such as phenylalanine or leucine did not disrupt binding
      to obscurin. Our results suggest that hydrophobic interactions contribute to the
      higher affinity of Obsc6316-6345 for sAnk1 and to the dominant role exhibited by
      this sequence in binding.

PMID- 22416965
TI  - Molecular organization of the non-bilayer phospholipid arrangements that induce
      an autoimmune disease resembling human lupus in mice.
AB  - Non-bilayer phospholipid arrangements are three-dimensional structures that can
      form when anionic phospholipids with an intermediate form of the tubular
      hexagonal phase II (H(II)), such as phosphatidic acid, phosphatidylserine or
      cardiolipin, are present in a bilayer of lipids. The drugs chlorpromazine and
      procainamide, which trigger a lupus-like disease in humans, can induce the
      formation of non-bilayer phospholipid arrangements, and we have previously shown
      that liposomes with non-bilayer arrangements induced by these drugs cause an
      autoimmune disease resembling human lupus in mice. Here we show that liposomes
      with non-bilayer phospholipid arrangements induced by Mn2+ cause a similar
      disease in mice. We extensively characterize the physical properties and
      immunological reactivity of liposomes made of the zwitterionic lipid
      phosphatidylcholine and a H(II)-preferring lipid, in the absence or presence of
      Mn2+, chlorpromazine or procainamide. We use an hapten inhibition assay to define
      the epitope recognized by sera of mice with the disease, and by a monoclonal
      antibody that binds specifically to non-bilayer phospholipid arrangements, and we
      report that phosphorylcholine and glycerolphosphorylcholine, which form part of
      the polar region of phosphatidylcholine, are the only haptens that block the
      binding of the tested antibodies to non-bilayer arrangements. We propose a model
      in which the negatively charged H(II)-preferring lipids form an inverted micelle
      by electrostatic interactions with the positive charge of Mn2+, chlorpromazine or
      procainamide; the inverted micelle is inserted into the bilayer of
      phosphatidylcholine, whose polar regions are exposed and become targets for
      antibody production. This model may be relevant in the pathogenesis of human
      lupus.

PMID- 22416966
TI  - Quality nursing care in Australian paediatric hospitals: a Delphi approach to
      identifying indicators.
AB  - AIM: To identify indicators of quality nursing care by identifying structures,
      processes and outcomes perceived as valid, feasible, reliable and suitable for
      Australian paediatric hospitals by nursing experts. BACKGROUND: Although
      measuring the quality of nursing care in acute care settings is being practised,
      there are few indicators validated for use in paediatric nursing. Using adult
      indicators for quality care measures in children's nursing has inherent problems.
      To contribute to quality improvement and safety in the paediatric population, it
      is essential to identify and validate indicators that will be useful in this
      context. DESIGN: A modified Delphi technique. METHOD: Fifty-seven indicators that
      potentially measure the quality of nursing care in paediatrics were identified
      following a review of the literature. Three online surveys where panellists rated
      these indicators for perceived validity in paediatric nursing, feasibility of
      data collection, reliability based on existing documentation and suitability in
      the paediatric context were completed between March-May 2010. RESULTS: Fifty-two
      nurses contributed to the expert panel. Consensus of 75% for validity in
      paediatric nursing was reached on 42 indicators, which were then ranked for
      suitability of use. Nineteen indicators were deemed inappropriate, which included
      indicators commonly used in adult settings. CONCLUSION: Face and content validity
      were reached for 42 indicators identified as potential valid measures of quality
      care in paediatric nursing. Further work is required to solve issues of
      reliability and feasibility of data collection and to ascertain whether the
      indicators occur frequently enough within Australian hospitals to be clinically
      useful. RELEVANCE TO CLINICAL PRACTICE: Identification of nursing-sensitive
      indicators that are valid in the paediatric setting is the first step in
      measuring the quality of care provided to children. Once established, measurement
      of the indicators may lead to improved patient safety and care in hospitals.

PMID- 22416967
TI  - Defensive coping, urbanization, and neuroendocrine function in Black Africans:
      the THUSA study.
AB  - Dissociation between beta-adrenergic behavioral and physiological defensive
      active coping (AC) responses was associated with cardiometabolic risk in urban
      but not rural African males. Whether this is partly driven by underlying
      neuroendocrine dysfunction is not certain. We aimed to assess the association
      between coping style, urbanization, and neuroendocrine function. Blood pressure
      (BP) and serum stress hormones were assessed across levels of urbanization (rural
      vs. urban) and coping style (active vs. passive) in 178 Black African men. Urban
      men demonstrated increased hypertension prevalence, alpha-adrenergic hemodynamic
      pattern, lower testosterone levels, and a larger cortisol:testosterone ratio
      (Cort:Test) compared to their rural counterparts. This was particularly evident
      in urban AC men where cortisol and Cort:Test explained 36-40% of the variance in
      BP. Dissociation between behavioral and physiological beta-adrenergic
      neuroendocrine responses in urban AC African men was shown. A stressful urban
      environment might induce an apparent loss of physiological control, thereby
      facilitating disturbed neuroendocrine AC responses, which could increase
      cardiovascular disease risk.

PMID- 22416969
TI  - Erosive esophagitis may be related to small intestinal bacterial overgrowth.
AB  - OBJECTIVES: Erosive esophagitis (EE) may be related to small intestinal bacterial
      overgrowth (SIBO) because gastro-esophageal reflux disease has been a comorbid
      condition of irritable bowel syndrome (IBS), which has been associated with SIBO.
      We conducted a pilot study to investigate whether EE was associated with SIBO.
      MATERIAL AND METHODS: Twenty-eight patients with EE according to the Los Angeles
      classification criteria and 29 sex- and age-matched subjects without EE were
      enrolled. All subjects underwent esophagogastroduodenoscopy and a lactulose
      hydrogen breath test. A peak of H2 values >20 ppm above the basal value after 10
      g of lactulose ingestion was considered abnormal and suggestive of SIBO. RESULTS:
      Abnormal lactulose hydrogen breath test results were found in 67% of EE patients,
      as compared with 37% in the control group; the difference was statistically
      significant (p = 0.024). Among the subjects without IBS, subjects with EE and
      controls had 65% and 31% abnormal lactulose hydrogen breath test results,
      respectively; the difference was also statistically significant (p = 0.032).
      CONCLUSIONS: Subjects with EE had a higher prevalence of SIBO, as assessed by the
      lactulose hydrogen breath test, with respect to a control group. These findings
      may suggest that EE is associated with SIBO.

PMID- 22416968
TI  - Lichen planus and lichenoid drug-induced eruption: a histological and
      immunohistochemical study.
AB  - INTRODUCTION: Lichenoid drug eruption (LDE) shares similar features with lichen
      planus (LP), that could reflect the same pathogenesis. In LP, an autoimmune
      attack is accepted and cytotoxic T-lymphocytes (CD8+) predominate, especially in
      late lesions. Apoptosis of keratinocytes may be mediated by CD8+ T and NK cells
      in two distinct ways: by the release of cytotoxic molecules such as perforin and
      granzyme B or by the Fas/FasL system. The immunological mechanisms involved in
      LDE are not yet fully established. OBJECTIVES: Investigate immunohistological
      features in LP and LDE to add clues to better understand their pathogenesis.
      MATERIAL AND METHODS: Twenty-two patients fulfilled all clinical, laboratory,
      histopathological, and follow-up features of lichen planus (n = 16) and lichenoid
      drug eruption (n = 6). Classic histological features favoring LP or LDE were
      evaluated by two observers. HAM56, MAC387, UCHL-1, OPD4, CD8, Granzyme B,
      Perforin, and ICAM-1 antibodies were used to decorate the immune infiltrate.
      Results were analyzed through Pearson correlation, Student's t-test, and linear
      discriminant analysis. RESULTS: A higher number of necrotic keratinocytes as well
      as plasma cells and eosinophils within inflammatory cells were associated with
      LDE diagnosis. Only in LDE, a correlation was found between the number of T and
      CD8+ cells and between the number of granzyme B+ cells and apoptotic
      keratinocytes. CONCLUSION: Our findings suggest a more important role of CD8+
      granzyme B-containing cells in LDE group, being its synthesis associated with
      more intense apoptosis. So, LP and LDE may have a somewhat distinct pathogenesis.

PMID- 22416970
TI  - Formation and regulation of the cancer stem cell niche.
AB  - It is widely accepted that tumors contain cancer stem cells (CSC) possessing self
      renewal potential as well as the ability to generate numerous cancer cells.
      Cancer stem cells are resistant to conventional cancer therapy and have greater
      invasive and metastatic behavior. It has been suggested that blood vessels
      provide a niche that maintains stemness in normal organs. This role also extends
      to the field of cancer biology. Cancer stem cells have been isolated from
      leukemias and solid cancers. Identification of these cells and their niche is
      critical for identifying molecular targets in order to inhibit their growth and
      to destroy their niche. For this purpose, sorting of living CSC is required to
      monitor their presence in the presumptive niche to establish whether a CSC
      candidate actually shows malignant features. Based on and referring to analyses
      in normal tissues, molecules including nitric oxide, Wnt, neuropilin-1,
      hepatocyte growth factor and others involved in the maintenance of CSC have been
      isolated. Stem cells might affect niche cells and niche cells produce stemness
      factors on such stimulation. Therefore, the niche might be flexible to support
      self-renewal or differentiation of stem cells even in the same niche cells.

PMID- 22416971
TI  - Magnetically actuated artificial cilia: the effect of fluid inertia.
AB  - Natural cilia are hairlike microtubule-based structures that are able to move
      fluid on the micrometer scale using asymmetric motion. In this article, we follow
      a biomimetic approach to design artificial cilia lining the inner surfaces of
      microfluidic channels with the goal of propelling fluid. The artificial cilia
      consist of polymer films filled with superparamagnetic nanoparticles, which can
      mimic the motion of natural cilia when subjected to a rotating magnetic field. To
      obtain the magnetic field and associated magnetization local to the cilia, we
      solve the Maxwell equations, from which the magnetic body moments and forces can
      be deduced. To obtain the ciliary motion, we solve the dynamic equations of
      motion, which are then fully coupled to the Navier-Stokes equations that describe
      the fluid flow around the cilia, thus taking full account of fluid inertial
      forces. The dimensionless parameters that govern the deformation behavior of the
      cilia and the associated fluid flow are arrived at using the principle of virtual
      work. The physical response of the cilia and the fluid flow for different
      combinations of elastic, fluid viscous, and inertia forces are identified.

PMID- 22416972
TI  - Kangaroo mother care may help oral growth and development in premature infants.
AB  - Premature infants have a shorter prenatal development period and are prone to
      many serious medical problems during neonatal period. This may impact the
      development of oral tissues, as manifested by enamel hypoplasia, palatal
      distortion, malocclusion, or delay in tooth eruption and maturation. Kangaroo
      mother care (KMC) is a standardized and protocol-based care system for premature
      infants, based on skin-to-skin contact between the infant and their mother.
      Kangaroo mother care has been demonstrated to greatly improve the nurturing of
      premature infants and comparatively reduce the risk factors of oral defects. We
      hypothesize that KMC also facilitates oral growth and development in premature
      infants.

PMID- 22416974
TI  - Synthesis of gem-difluoromethylenated bicyclo[m.n.0]alkan-1-ols and their ring
      expansion to gem-difluoromethylenated macrocyclic lactones.
AB  - Fluoride-catalyzed stereoselective nucleophilic addition of PhSCF(2)SiMe(3) (1)
      to alpha-carboethoxycycloalkanones 2 followed by intramolecular radical
      cyclization of the resulting cis-3 adduct afforded the corresponding gem
      difluoromethylenated bicyclic compounds 4, which underwent ring-expansion
      followed by the Baeyer-Villiger-type oxidation of the resulting macrocyclic
      ketone intermediates to give gem-difluoromethylenated macrocyclic lactones 5.

PMID- 22416973
TI  - Continuous high-frequency activity in mesial temporal lobe structures.
AB  - PURPOSE:   Many recent studies have reported the importance of high-frequency
      oscillations (HFOs) in the intracerebral electroencephalography (EEG) of patients
      with epilepsy. These HFOs have been defined as events that stand out from the
      background. We have noticed that this background often consists itself of high
      frequency rhythmic activity. The purpose of this study is to perform a first
      evaluation of the characteristics of high-frequency continuous or semicontinuous
      background activity. METHODS:   Because the continuous high-frequency pattern was
      noted mainly in mesial temporal structures, we reviewed the EEG studies from
      these structures in 24 unselected patients with electrodes implanted in these
      regions. Sections of background away from interictal spikes were marked visually
      during periods of slow-wave sleep and wakefulness. They were then high-passed
      filtered at 80 Hz and categorized as having high-frequency rhythmic activity in
      one of three patterns: continuous/semicontinuous, irregular, sporadic. Wavelet
      entropy, which measures the degree of rhythmicity of a signal, was calculated for
      the marked background sections. KEY FINDINGS:   Ninety-six bipolar channels were
      analyzed. The continuous/semicontinuous pattern was found frequently (29/96
      channels during wake and 34/96 during sleep). The different patterns were
      consistent between sleep and wakefulness. The continuous/semicontinuous pattern
      was found significantly more often in the hippocampus than in the parahippocampal
      gyrus and was rarely found in the amygdala. The types of pattern were not
      influenced by whether a channel was within the seizure-onset zone, or whether it
      was a lesional channel. The continuous/semicontinuous pattern was associated with
      a higher frequency of spikes and with high rates of ripples and fast ripples.
      SIGNIFICANCE:   It appears that high-frequency activity (above 80 Hz) does not
      appear only in the form of brief paroxysmal events but also in the form of
      continuous rhythmic activity or very long bursts. In this study limited to mesial
      temporal structures, we found a clear anatomic preference for the hippocampus.
      Although associated with spikes and with distinct HFOs, this pattern was not
      clearly associated with the seizure-onset zone. Future studies will need to
      evaluate systematically the presence of this pattern, as it may have a
      pathophysiologic significance and it will also have an important influence on the
      very definition of HFOs.

PMID- 22416975
TI  - Histological spectrum of pulmonary manifestations in kidney transplant recipients
      on sirolimus inclusive immunosuppressive regimens.
AB  - BACKGROUND: After the introduction of novel effective immunosuppressive
      therapies, kidney transplantation became the treatment of choice for end stage
      renal disease. While these new therapies lead to better graft survival, they can
      also cause a variety of complications. Only small series or case reports describe
      pulmonary pathology in renal allograft recipients on mTOR inhibitor inclusive
      therapies. The goal of this study was to provide a systematic review of thoracic
      biopsies in kidney transplant recipients for possible association between a type
      of immunosuppressive regimen and pulmonary complications. METHODS: A laboratory
      database search revealed 28 of 2140 renal allograft recipients (18 males and 10
      females, 25 to 77 years old, mean age 53 years) who required a biopsy for
      respiratory symptoms. The histological features were correlated with clinical
      findings including immunosuppressive medications. RESULTS: The incidence of
      neoplasia on lung biopsy was 0.4% (9 cases), which included 3 squamous cell
      carcinomas, 2 adenocarcinomas, 1 diffuse large B-cell lymphoma, 1 lymphomatoid
      granulomatosis, and 2 post transplant B-cell lymphoproliferative disorders.
      Diffuse parenchymal lung disease was identified in 0.4% (9 cases), and included 5
      cases of pulmonary hemorrhage, 3 cases of organizing pneumonia and 1 case of
      pulmonary alveolar proteinosis. Five (0.2%) cases showed histological features
      indicative of a localized infectious process. Patients on sirolimus had neoplasia
      less frequently than patients on other immunosuppressive combinations (12.5% vs.
      58.3%, p = 0.03). Lung biopsies in 4 of 5 patients with clinically suspected
      sirolimus toxicity revealed pulmonary hemorrhage as the sole histological finding
      or in combination with other patterns. CONCLUSIONS: Our study documents a
      spectrum of neoplastic and non-neoplastic lesions in renal allograft recipients
      on current immunosuppressive therapies. Sirolimus inclusive regimens are
      associated with increased risk of pulmonary toxicity but may be beneficial in
      cases of posttransplant neoplasia. VIRTUAL SLIDES: The virtual slide(s) for this
      article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/3320012126569395.

PMID- 22416976
TI  - The Study of Nursing Care project: back to the future for contemporary nursing
      research?
AB  - AIMS:   To discuss the Study of Nursing Care project, an initiative from the late
      1970s in the UK. The article explores the impact of the Study of Nursing Care on
      nursing research, and considers to what extent it presents a useful model for
      contemporary nursing research. BACKGROUND:   It is acknowledged internationally
      that the nursing academic workforce is ageing and dwindling. Many possible
      solutions are being debated with all agreeing that the next generation of
      evidence based nurse leaders is urgently required. DATA SOURCES:   In this
      article, the authors survey existing workforce schemes, describe the Study of
      Nursing Care series, published in the 1970s, and draw on interviews and
      correspondence conducted in 2009 with four of the original Study of Nursing Care
      research assistants. DISCUSSION:   The Study of Nursing Care project poses a
      potential response to academic workforce issues. This article discusses the
      evolution of the project, its methods and operation and considers its possible
      implications for contemporary practice. Implications for nursing.  The Study of
      Nursing Care model demonstrates the clear benefits of fully committed funding, a
      programmatic approach towards research development, and the importance of
      selecting the right kind of people for the work, in a national scheme.
      CONCLUSION:   The authors argue that although the clinical outcomes it set out to
      achieve remain elusive, the project produced a cohort of nurse researchers who
      went on to give important leadership in nursing, including in nursing
      academia/research. A contemporary version of the Study of Nursing Care has
      important potential to generate the next generation of nurse researchers, and
      leaders, into the twenty-first century.

PMID- 22416977
TI  - Effect of tea catechins on regulation of cell proliferation and antioxidant
      enzyme expression in H2 O2 -induced primary hepatocytes of goat in vitro.
AB  - Tea catechins (TC) are polyphenols that have potent antioxidant activity. The
      objectives of this study were to determine the effects of TC on antioxidant
      status of hepatocytes challenged with H2 O2 . Primary hepatocytes of goat were
      exposed to 1 mm H2 O2 without or with 5, 50 and 500 MUg/ml TC. The cells were
      harvested at 48 h post-treatment to determine effects of TC on proliferation,
      apoptotic features and membrane integrity of cells, and expression of genes and
      activities of antioxidant enzymes. H2 O2 exposure caused damage to cells (p <
      0.001). A lower concentration of TC (5 MUg/ml) displayed a protective effect by
      inhibiting exorbitant cell proliferation and DNA degradation. Both H2 O2 exposure
      and TC pre-incubation affected expression of antioxidant enzymes at mRNA and
      protein levels (p < 0.001). The activities of catalase (CAT) (p = 0.027), CuZn
      superoxide dismutase (CuZn-SOD) (p < 0.001) and glutathione peroxidase (GPx) (p <
      0.001) increased with TC pre-incubation followed by H2 O2 challenge. Changes of
      CuZn-SOD activity induced by H2 O2 and TC basically paralleled the changes in the
      corresponding mRNA and protein levels, but the correlation in CAT and GPx
      expression displayed slightly different patterns at different concentrations of
      TC. These findings infer that oxidative stress can induce deleterious cellular
      responses and this unfavourable condition may be alleviated by treatment with TC.

PMID- 22416978
TI  - Rapid and highly sensitive dual-channel detection of cyanide by bis-heteroleptic
      ruthenium(II) complexes.
AB  - Two new ruthenium complexes [Ru(bipy)(2)(PDA)](2+) (1) and [Ru(phen)(2)(PDA)](2+)
      (2) (PDA = 1,10-phenanthroline-4,7-dicarboxaldehyde) have been synthesized to
      detect cyanide based on the well-known formation of cyanohydrins. Both
      1[PF(6)](2) and 2[PF(6)](2) were fully characterized by various spectroscopic
      techniques and their solid state structures determined by single-crystal X-ray
      diffraction. Their anion binding properties in pure and aqueous acetonitrile were
      thoroughly examined using two different channels, i.e., UV-vis absorption and
      photoluminescence (PL). After addition of only 2 equiv of CN(-), the PL intensity
      of 1[PF(6)](2) and 2[PF(6)](2) was enhanced ~55-fold within 15 s along with a
      diagnostic blue shift of the emission by more than 100 nm. PL titrations of
      1[PF(6)](2) and 2[PF(6)](2) with CN(-) in CH(3)CN furnished the very high overall
      cyanohydrin formation constants log beta([CN(-)]) = 15.36 +/- 0.44 (beta([CN(-)])
      = 2.3 * 10(15) M(-2)) and log beta([CN(-)]) = 16.37 +/- 0.53 (beta([CN(-)]) = 2.3
      * 10(16) M(-2)), respectively. For both probes, the second constant, K(2), is
      about 57-84 times less than K(1), suggesting that the cyanohydrin reaction is
      stepwise. The stepwise mechanism is further supported by results of a (1)H NMR
      titration of 2[PF(6)](2) with CN(-). The high selectivity of 2[PF(6)](2) for CN(
      ) was established by PL in the presence of other competing anions. Furthermore,
      the color change from orange-red to yellow and the appearance of a orange
      luminescence, which can be observed by the naked eye, provides a simple real-time
      method for cyanide detection. Finally, theoretical calculations were carried out
      to elucidate the details of the electronic structure and transitions involved in
      the ruthenium probes and their cyanide adducts.

PMID- 22416979
TI  - A case-only study of gene-environment interaction between genetic susceptibility
      variants in NOD2 and cigarette smoking in Crohn's disease aetiology.
AB  - BACKGROUND: Genetic variation in NOD2 and cigarette smoking are well-established
      risk factors for the development of Crohn's disease (CD). However, little is
      known about a potential interaction between these risk factors. We investigated
      gene-environment interactions between CD-associated NOD2 alleles and cigarette
      smoking in a large sample of patients with CD. METHODS: Three previously reported
      CD-associated variants in NOD2 (R702W, G908R, 1007fs) were genotyped in 1636
      patients with CD continuously recruited between 1995 and 2010 based on physician
      referral. Data on history of smoking behaviour was obtained for all participants
      through a written questionnaire. Using a case-only design, we performed logistic
      regression analyses to investigate statistical interactions between NOD2 risk
      alleles and smoking status. RESULTS: We detected a significant negative
      interaction between carriership of at least one of the NOD2 risk alleles and
      history of ever having smoked (OR = 0.71; p = 0.005) as well as smoking at the
      time of CD diagnosis (OR = 0.68; p = 0.005). Subsequent separate analyses of the
      three variants revealed a significant negative interaction between the 1007fs
      variant and history of ever having smoked (OR = 0.64; p = 9 * 10-4) and smoking
      at the time of CD diagnosis (OR = 0.53; p = 7 * 10-5). CONCLUSIONS: The observed
      significant negative gene-environment interaction suggests that the risk increase
      for CD conferred simultaneously by cigarette smoking and the 1007fs NOD2
      polymorphism is smaller than expected and may point to a biological interaction.
      Our findings warrant further investigation in epidemiological and functional
      studies to elucidate pathophysiology as well as to aid in the development of
      recommendations for disease prevention.

PMID- 22416980
TI  - Cholesteryl-functionalized ADNF-9 peptide: enhanced membrane transport through
      mouse neuroblastoma Neuro-2a cells.
AB  - A cholesteryl-functionalized derivative of activity dependent neurotrophic factor
      9 peptide (a nine amino acid core peptide of activity-dependent neurotrophic
      factor, acting against Alzheimer's disease) was synthesized aiming at the
      improvement of its bioavailability. Therefore, its uptake was comparatively
      investigated with that of its parent peptide by employing mouse neuroblastoma
      Neuro-2a cells. Owing to the hydrophobic character of this cholesteryl
      functionalized peptide, it exhibited enhanced permeability and intracellular
      uptake while it also retained its low cytotoxicity at concentrations up to 1 MUM.
      FACS analysis also revealed that when Neuro-2a cells were treated with this
      activity dependent neurotrophic factor-9 derivative, at a concentration of 50 nM,
      an almost 100% uptake was obtained. In addition, in vitro biological activity
      experiments showed that the functionalized peptide retained its neurotrophic
      activity at femtomolar concentration range.

PMID- 22416981
TI  - Influence of capsaicin on fluctuation of digoxin pharmacokinetics in
      lipopolysaccharide-treated rats.
AB  - In the present study, we investigated the influence of Cap on digoxin
      pharmacokinetics in lipopolysaccharide (LPS)-treated rats. After the oral
      administration of digoxin (0.1 mg/kg), the area under the plasma concentration
      time curve (AUC) of digoxin increased significantly until day 3 after LPS
      treatment. In the LPS + Cap group, the recovery period of AUC was shortened to 3
      days. On days 5 and 7, the maximum plasma concentrations decreased significantly
      as compared to the control group. The bioavailability of digoxin in LPS group was
      higher than that in the LPS + Cap group. The hepatic cytochrome P450 (CYP) 3A2
      content decreased significantly until day 5 after LPS administration, but it
      returned to the control level until 5 days in the LPS + Cap group. Hepatic CYP3A2
      mRNA expression of LPS group decreased significantly until day 3, but it returned
      to the control level on day 3 and increased significantly until day 7 in the LPS
      + Cap group. The DNA-binding activity of pregnane X receptor (PXR) was increased
      on days 3-7 in the Cap and LPS + Cap group. Cap decreased the absorption of
      digoxin by inducing CYP3A2 mRNA expression via indirect activation of PXR in LPS
      treated rats.

PMID- 22416984
TI  - Dental implants in frail elderly adults: a benefit or a liability?

PMID- 22416982
TI  - Pharmacokinetic and pharmacodynamic interaction between nifedipine and metformin
      in rats: competitive inhibition for metabolism of nifedipine and metformin by
      each other via CYP isozymes.
AB  - It has been reported that hypertension exponentially increases in the patients
      with type 2 diabetes mellitus. Thus, this study was performed to investigate the
      pharmacokinetic and pharmacodynamic interactions between nifedipine and
      metformin, since both drugs were commonly metabolized via hepatic CYP2C and 3A
      subfamilies in rats. Nifedipine (3 mg/kg) and metformin (100 mg/kg) were
      simultaneously administered intravenously or orally to rats. Concentrations (I)
      of each drug in the liver and intestine, maximum velocity (V(max)), Michaelis
      Menten constant (K(m)), and intrinsic clearance (CL(int)) for the disappearance
      of each drug, apparent inhibition constant (K(i)) and [I]/K(i) ratios of each
      drug in liver and intestine were determined. Also the metabolism of each drug in
      rat and human CYPs and blood pressure were also measured. After the simultaneous
      single intravenous administration of both drugs together, the AUCs of each drug
      were significantly greater than that in each drug alone due to the competitive
      inhibition for the metabolism of nifedipine by metformin via hepatic CYP3A1/2 and
      of metformin by nifedipine via hepatic CYP2C6 and 3A1/2. After the simultaneous
      single oral administration of both drugs, the significantly greater AUCs of each
      drug than that in each drug alone could have mainly been due to the competitive
      inhibition for the metabolism of nifedipine and metformin by each other via
      intestinal CYP3A1/2 in addition to competitive inhibition for the hepatic
      metabolism of each drug as same as the intravenous study.

PMID- 22416985
TI  - Dental service trends for older US adults, 1998-2006.
AB  - This study of the Medicare Current Beneficiary Survey (MCBS) updates trends in
      utilization of dental services between 1998 and 2006 for community-dwelling U.S.
      adults of age 65 years and older. Bivariate comparisons were made between
      dependent variables (annual dental visits and types of dental procedures) and
      independent variables (age, gender, race, income, education, population density,
      marital status, U.S. Census Bureau regions, and self-reported health). The
      estimated percentage of community-dwelling Medicare beneficiaries with a dental
      visit for the years studied increased from 45.0% in 1998 to 46.3% in 2006. The
      age group of respondents who were 85 years and older had the greatest percentage
      increase in dental visits. Those reporting visits with preventive procedures
      increased from 87.8% to 91.2% whereas those reporting visits with nonpreventive
      procedures declined from 63.9% to 58.4%. The prevalence of dental visits
      continues to trend upward for this population of older adults. Increasing
      delivery of preventive services will likely impact the future mix of dental
      services as U.S. adults live longer.

PMID- 22416986
TI  - Oral status, oral hygiene, and patient satisfaction in the elderly with dental
      implants dependent on substantial needs of care for daily living.
AB  - Using osseointegrated implants to replace teeth is a routine procedure today.
      This study investigated oral status, oral hygiene habits, and patient
      satisfaction in elderly with dental implants who were dependent on substantial
      support for daily living. Twenty-six persons over the age of 65 who were
      dependent on supportive care were examined. Data collected included the number of
      teeth and implants, plaque scores, bleeding on probing, and oral hygiene habits.
      Self-perceived knowledge about managing their implants and satisfaction with the
      implants was recorded. Subjects had a total of 148 natural teeth and 144
      implants. Only a few signs of oral disease were found and the tissues around
      implants were healthier than around natural teeth. No correlations between oral
      hygiene habits and plaque scores or bleeding were found. A majority of the
      subjects were satisfied with their implants. Dental implants have satisfactory
      function even in individuals who are elderly and have substantial needs for
      supportive care.

PMID- 22416987
TI  - Sickle cell disease does not predispose to caries or periodontal disease.
AB  - This study investigated the prevalence of dental caries and periodontal condition
      in a population with sickle cell disease (SCD), analyzing some associations with
      disease severity. The Decayed, Missing and Filled Teeth index (DMFT) and
      Community Periodontal Index (CPI) were recorded for 99 individuals with SCD and
      91 matched controls. Socio-demographic status, oral health behaviors, and history
      of clinical severity of SCD were assessed. Statistical comparisons were performed
      between the group with SCD and the control group, as well as multivariate
      logistic regression analyses with DMFT index and CPI as the dependent variables.
      The mean number of decayed teeth was significantly higher in individuals with
      HbSS. Older age, female gender, and daily smoking were identified as risk factors
      for higher DMFT, while older age and absence of daily use of dental floss were
      risk factors for the development of periodontal disease. In conclusion, risk
      factors known to cause caries and periodontal disease had more influence on oral
      health than the direct impact of SCD.

PMID- 22416988
TI  - Adjunctive use of tetracycline fibers with nonsurgical periodontal therapy in an
      adult with Down syndrome: a case report.
AB  - Individuals with Down syndrome (DS) are susceptible to severe periodontal
      disease, due to immune alterations related to functional defects of
      polymorphonuclear leukocytes and monocytes. The adjunctive use of locally
      delivered antimicrobials has been proven to be beneficial, especially in areas
      where mechanical therapy might fail. This article describes the management of a
      patient with DS who had aggressive periodontitis. The treatment used a local drug
      delivery system with tetracycline fibers as an adjunct to scaling and root
      planing.

PMID- 22416989
TI  - Periodontal findings in a patient with Mauriac syndrome: a case report.
AB  - Mauriac syndrome is a rare condition that affects people with uncontrolled
      diabetes. The case history of a 17-year-old female patient diagnosed with Mauriac
      syndrome and concurrently suffering from type 1 diabetes mellitus (T1DM), stunted
      growth, hepatomegaly, and severe periodontal disease is described. Non-surgical
      periodontal therapy was the treatment provided. Severe periodontal destruction
      was seen in conjunction with the unique features of this syndrome, such as
      hepatomegaly, dwarfism, moon-shaped face, cushingoid fat deposition, delayed
      puberty, and brittle diabetes. Treatment resulted in decreased plaque and
      gingival scores. A bi-directional relationship has been established between
      diabetes mellitus and periodontal disease and there is an increasing emphasis on
      perio-systemic interrelationships. Given the effect that such systemic disorders
      have on periodontal health, periodontists should be involved in the early
      diagnosis and treatment of such patients.

PMID- 22416990
TI  - Oral characteristics of a patient with Ekman-Westborg-Julin trait: a case
      history.
AB  - This article presents the case of a Japanese woman who had Ekman-Westborg-Julin
      trait. She had general macrodontia with multituberculism, evagination of the
      premolar, single conical roots, shovel-shaped incisors, enamel hypoplasia,
      impacted tooth, dental crowding, and an open bite. The oral and general
      characteristics of this patient are described and include the histological and
      radiographic findings of the mandibular third molars. We suggest that the
      distinctive oral features with macrodontia of the permanent teeth,
      multituberculism, evagination, single conical roots, and impaction of the tooth
      could be defined as the Ekman-Westborg-Julin trait.

PMID- 22416992
TI  - pCERC1, a small, globally disseminated plasmid carrying the dfrA14 cassette in
      the strA gene of the sul2-strA-strB gene cluster.
AB  - Commensal Escherichia coli from healthy adult humans were screened for antibiotic
      resistance genes. Two unrelated strains contained the sul2 sulphonamide
      resistance gene and strAB streptomyicn resistance genes with the dfrA14
      trimethoprim resistance gene cassette in the strA gene and conferred resistance
      to trimethoprim and sulphamethoxazole. A 6.8 kb plasmid, pCERC1, that contains
      these resistance genes was recovered and sequenced. Deletions were constructed,
      and the pCERC1 replication region was confined to a 1 kb segment carrying genes
      for RNAs that are closely related to the ColE1 replication initiation RNAs.
      Polymerase chain reaction assays, developed to detect the sul2-strA-strB gene
      cluster in this context, identified a streptomycin and sulphonamide resistance
      plasmid, pCERC2, identical to pCERC1 without the dfrA14 cassette in two further
      E. coli isolates. Bioinformatic analysis revealed plasmids similar to pCERC1 and
      two more members of this family. One, the probable progenitor, carries only the
      sul2 gene adjacent to the small mobile element CR2. The other has a variant
      resistance gene cluster that has evolved from pCERC2 via acquisition of the
      tet(A) tetracycline resistance determinant. pCERC1 and pCERC2 have been detected
      in many countries, indicating a global distribution and appear to have been
      circulating in Gram-negative bacteria for more than 25 years.

PMID- 22416993
TI  - A loop-mediated isothermal amplification method for rapid detection of NDM-1
      gene.
AB  - A loop-mediated isothermal amplification (LAMP) method was developed for the
      rapid and sensitive detection of the emerging resistance gene New Delhi Metallo
      beta-lactamase-1 (NDM-1), with its specificity and sensitivity having been
      evaluated. Six primers, including a pair of outer primers, a pair of inner
      primers, and a pair of loop primers, were specially designed for recognizing
      eight distinct sequences on the target NDM-1 gene. The amplification reaction was
      performed within only 40 min under isothermal conditions at 65 degrees C in a
      regular water bath. The LAMP assay showed good specificity and higher sensitivity
      than the conventional polymerase chain reaction (PCR), with a detection limit of
      1 pg genomic DNA per tube of one NDM-1-positive reference strain. The detection
      result for the 345 clinical samples showed 100% consistence with the result by
      the PCR method, and three contaminated samples could be detected correctly by
      LAMP assays, while they could not be detected by PCR. The LAMP method reported
      here demonstrated a potential and valuable means for detection of the NDM-1 gene:
      easy, rapid, visual, specific, accurate, and sensitive, especially useful for on
      the-spot investigation.

PMID- 22416994
TI  - Effects of acculturation and social network support on depression among elderly
      Korean immigrants.
AB  - OBJECTIVE: Acculturation and social network support have been identified as
      predictors of mental health for immigrant and elderly populations. The present
      study examined both independent and interactive effects of acculturation and
      social network support on depressive symptomatology among elderly Korean
      immigrants. METHOD: Self-reported measures included sociodemographic
      characteristics, acculturation, social network support, and depressive symptoms.
      This study used cross-sectional analysis of a community-based cohort. RESULTS:
      After controlling for the effects of demographic variables, a robust hierarchical
      regression model indicated that social network support was negatively associated
      with depressive symptoms. Also, the interaction between acculturation and social
      network was significantly associated with lower levels of depressive symptoms
      (beta = -0.29, p < 0.05). In other words, elderly Korean immigrants who had high
      social network support and were highly acculturated exhibited lower levels of
      depression compared to those who had low support and were highly acculturated.
      CONCLUSION: Our findings call attention to the role of social network support in
      the mental health of elderly Korean immigrants. Service providers can develop
      strategies for decreasing depression by increasing social network support,
      especially with family members, among their elderly parents.

PMID- 22416995
TI  - Nodular melanoma arising in a patient treated with anti-tumor necrosis factor
      alpha antagonists.

PMID- 22416996
TI  - Simvastatin interactions with other drugs.
AB  - INTRODUCTION: Statins, the mainstay of lipid-lowering therapy, are among the most
      commonly used drugs due to their beneficial effects in cardiovascular morbidity
      and mortality. Simvastatin, one of the most well-studied statins, is available in
      several generic forms both as monotherapy and with ezetimibe and is frequently
      prescribed worldwide. Despite its overall favorable risk profile, several
      previously stated concerns regarding high-dose simvastatin were recently
      formalized by the Food and Drug Administration (FDA). AREAS COVERED: This paper
      discusses the interactions between simvastatin and other drugs and presents the
      latest FDA recommendations regarding the safe use of this statin. Relevant
      articles were identified through a PubMed search (up to December 2011).
      Furthermore, the latest FDA warning (June 2011) regarding simvastatin use was
      taken into account. EXPERT OPINION: Simvastatin may have serious side effects
      particularly when used in high doses and in combination with certain drugs.
      Physicians need to adjust the recent recommendations made by the FDA in clinical
      practice in order to prevent treatment complications.

PMID- 22416997
TI  - Neural mechanisms underlying the orienting response to subject's own name: an
      event-related potential study.
AB  - Neural processes underlying the orienting response (OR) to subject's own name
      (SON) were investigated using the oddball paradigm. Subjects were presented with
      SON, subject's parent's name, and unfamiliar persons' names while they played a
      video game and ignored the auditory stimuli. A P3a-like frontal positivity (P440,
      440 ms) indexing OR was elicited by SON only when it was the rare stimulus and
      its amplitude decreased with the repeated presentation of SON. Preceding the
      P440, SON consistently elicited an early frontal negativity (SON negativity, 170
      270 ms), including when SON was the high-probability stimulus, and unlike the
      P440, this negativity did not habituate. These results conform to the hypothesis
      that early preattentive processing of speech sounds distinguishes SON from other
      names irrespective of short-term stimulus context, and that this culminates in an
      OR only when SON is evaluated as being contextually meaningful.

PMID- 22416998
TI  - The prevalence and natural history of urinary symptoms among recreational
      ketamine users.
AB  - Study Type--Symptom prevalence (prospective cohort) Level of Evidence 1b. What's
      known on the subject? and What does the study add? Case series have described
      lower urinary tract symptoms associated with ketamine use including severe pain,
      frequency, haematuria and dysuria. Little is known regarding the frequency of
      symptoms, relationship of symptoms with dose and frequency of use and natural
      history of symptoms once the ketamine user has stopped. This study describes the
      prevalence of ketamine use in a population of recreational drug users in a dance
      music setting. It shows a dose-frequency relationship with ketamine use. It shows
      that urinary symptoms associated with recreational ketamine use may lead to a
      considerable demand on health resources in the primary-, secondary- and emergency
      care settings. It shows that symptoms may improve once ketamine use is decreased.
      OBJECTIVE: * To investigate the prevalence and natural history of urinary
      symptoms in a cohort of recreational ketamine users. PATIENTS AND METHODS: * A
      purposeful sampling technique was used. * Between November 2009 and January 2010
      participants were invited to undertake an on-line questionnaire promoted by a
      national dance music magazine and website. * Data regarding demographics and
      illicit drug-use were collected. * Among respondents reporting recent ketamine
      use, additional information detailing their ketamine use, experience of urinary
      symptoms and use of related healthcare services was obtained. RESULTS: * In all,
      3806 surveys were completed, of which 1285 (33.8%) participants reported ketamine
      use within the last year. * Of the ketamine users, 17% were found to be dependent
      on the drug; 26.6% (340) of recent ketamine users reported experiencing urinary
      symptoms. * Urinary symptoms were significantly related to both dose of ketamine
      used and frequency of ketamine use. * Of 251 users reporting their experience of
      symptoms over time in relationship to their use of ketamine, 51% reported
      improvement in urinary symptoms upon cessation of use with only eight (3.8%)
      reporting deterioration after stopping use. CONCLUSIONS: * Urinary tract symptoms
      are reported in over a quarter of regular ketamine users. * A dose and frequency
      response relationship has been shown between ketamine use and urinary symptoms. *
      Both users and primary-care providers need to be educated about urinary symptoms
      that may arise in ketamine users. A multi-disciplinary approach promoting harm
      reduction, cessation and early referral is needed to manage individuals with
      ketamine-associated urinary tract symptoms to avoid progression to severe and
      irreversible urological pathologies.

PMID- 22416999
TI  - Collective mechanical behavior of multilayer colloidal arrays of hollow
      nanoparticles.
AB  - The collective mechanical behavior of multilayer colloidal arrays of hollow
      silica nanoparticles (HSNP) is explored under spherical nanoindentation through a
      combination of experimental, numerical, and theoretical approaches. The effective
      indentation modulus E(ind) is found to decrease with an increasing number of
      layers in a nonlinear manner. The indentation force versus penetration depth
      behavior for multilayer hollow particle arrays is predicted by an approximate
      analytical model based on the spring stiffness of the individual particles and
      the multipoint, multiparticle interactions as well as force transmission between
      the layers. The model is in good agreement with experiments and with detailed
      finite element simulations. The ability to tune the effective indentation
      modulus, E(ind), of the multilayer arrays by manipulating particle geometry and
      layering is revealed through the model, where E(ind) = (0.725m(-3/2) +
      0.275)E(mon) and E(mon) is the monolayer modulus and m is number of layers.
      E(ind) is seen to plateau with increasing m to E(ind_plateau) = 0.275E(mon) and
      E(mon) scales with (t/R)(2), t being the particle shell thickness and R being the
      particle radius. The scaling law governing the nonlinear decrease in indentation
      modulus with an increase in layer number (E(ind) scaling with m(-3/2)) is found
      to be similar to that governing the indentation modulus of thin solid films
      E(ind_solid) on a stiff substrate (where E(ind_solid) scales with h(-1.4) and
      also decreases until reaching a plateau value) which also decreases with an
      increase in film thickness h. However, the mechanisms underlying this trend for
      the colloidal array are clearly different, where discrete particle-to-particle
      interactions govern the colloidal array behavior in contrast to the substrate
      constraint on deformation, which governs the thickness dependence of the
      continuous thin film indentation modulus.

PMID- 22417001
TI  - Innovations aimed at improving the physical health of the seriously mentally ill:
      an integrative review.
AB  - AIMS AND OBJECTIVES: The aim of this paper is to report an integrative review of
      the literature that focused on innovations aimed at enhancing the physical health
      of people with serious mental illness. BACKGROUND: Despite the abundance of
      literature that highlights the relationship between serious mental illness and
      physical ill health, the provision of physical health care for the seriously
      mental ill remains a challenge. Many different strategies have been developed,
      which endeavour to address the poor physical health of people with serious mental
      illness. However, there is inadequate evidence to establish the success of these
      strategies. DESIGN: Integrative literature review. METHOD: The review was
      conducted using an adapted version of Whittemore and Knafl's review method to
      critically appraise and evaluate the literature. Results.  Three main themes
      derived for the types of intervention in the studies emerged from the review.
      These included assessment, health education/health promotion and multimodal
      interventions. CONCLUSION: Although there is some evidence to demonstrate that
      health assessments are effective in highlighting physical health problems, the
      evidence to support health education and multimodal interventions is far from
      conclusive. Further research is needed, in particular larger intervention and
      longitudinal studies, to help nurses decide on the best possible interventions
      that will improve the physical health of the seriously mentally ill. RELEVANCE TO
      CLINICAL PRACTICE: Whilst nurses' continued attempts to develop health-enhancing
      interventions are commendable, there needs to be a greater focus on conducting
      research to develop the evidence base to guide and support nurses in this area of
      their practice. Until robust and convincing evidence is available, policy
      relating to the advancement of the physical health of people with serious mental
      illness should be developed cautiously.

PMID- 22417000
TI  - Epstein-Barr virus-encoded LMP1 triggers regulation of the ERK-mediated
      Op18/stathmin signaling pathway in association with cell cycle.
AB  - The MAPKs are activated by a variety of cellular stimuli to participate in a
      series of signaling cascades and mediate diverse intracellular responses. One
      potential target of the MAPKs is Op18/stathmin, a molecule that acts as an
      integrator of diverse cell signaling pathways and regulates the dynamics of
      microtubules, which are involved in modulating a variety of cellular processes,
      including cell cycle progression and cell growth. Our study focused on the
      regulation of the MAPK-mediated Op18/stathmin signaling pathway, which is
      triggered by the Epstein-Barr virus-encoded latent membrane protein 1 ( LMP1)
      oncogene in nasopharyngeal carcinoma cells. The results showed that the activity
      of MAPK, which was induced by LMP1, varied with cell cycle progression; LMP1
      upregulated phosphorylation of ERK during the G(1)/S phase, but negatively
      regulated phosphorylation of ERK during the G(2)/M phase. We found that the
      regulation of Op18/stathmin signaling by LMP1 was mainly mediated through ERK.
      The inhibition of LMP1 expression attenuated the interaction of ERK with
      Op18/stathmin and promoted microtubule depolymerization. These findings indicate
      the existence of a new cell cycle-associated signaling pathway in which LMP1
      regulates ERK-mediated Op18/stathmin signaling.

PMID- 22417002
TI  - Liver morphologic analysis in perinatal autopsies with intrauterine stress liver
      morphology in perinatal autopsies.
AB  - Quantify steatosis, fibrosis, and focuses of extramedullary erythropoiesis (ER)
      in the liver and report it to the causes of death in the perinatal. Morphologic
      analysis of steatosis', percentage of fibrosis, and ER of 467 perinatal
      autopsies. Cases with hypoxia/perinatal anoxia and ascending infection showed
      higher percentage of fibrosis. The number of ER was significantly higher among
      premature infants and in cases with infection. Our results contribute to a better
      quality of perinatal care through clinical demonstration of which injuries are
      associated with them, what may help in early diagnosis of these alterations in
      children who survive.

PMID- 22417003
TI  - Onset of intractability and its course over time: the Dutch study of epilepsy in
      childhood.
AB  - PURPOSE: Intractability in epilepsy is difficult to define, and little is known
      about its onset, course, and duration. We investigated these aspects (as well as
      the occurrence of intractability) during long-term follow-up in patients with
      epilepsy, focusing on possible explanations for the variation in time of onset
      and duration of intractability. METHODS: After diagnosis, 453 patients with
      childhood-onset epilepsy had a 5-year follow-up with regular visits and data
      collection. Ten years later they received a questionnaire with items concerning
      epilepsy, which was completed by 413 patients resulting in a mean follow-up of 15
      years. Intractability during the first 5 years was compared with that in the last
      year of follow-up. Intractability was defined as having no 3-month remission
      during a 1-year period despite adequate medical treatment. KEY FINDINGS: At least
      12.1% of the cohort had a period of intractability during the 15-year follow-up,
      and 8.5% were intractable in the final year. Of the patients with idiopathic
      etiology 4.3% had a period of intractability versus 17.0% for those with
      cryptogenic, and 22.6% for those with remote symptomatic etiology (p < 0.001).
      Other risk factors at baseline were younger age at first seizure, generalized
      cryptogenic/symptomatic or localization-related symptomatic epilepsy, mental
      retardation, and febrile convulsions before enrollment. The cumulative risk of a
      period of intractability was 6.1% (95% confidence interval [CI] 3.7-8.5) at 2
      years follow-up and 8.2% (95% CI 5.4-11.0) at 5 years. The mean time to onset of
      intractability during the first 5 years of follow-up was 1.6 (95% CI 1.3-2.0;
      median 1.0) years and the mean duration of intractability during these 5 years
      was 3.3 (95% CI 2.8-3.8; median 3.6) years. Fifteen patients were intractable
      only during the first 5 years of follow-up (group A), and 19 subjects were
      intractable both during the first 5 years and the last year of follow-up (group
      B). Compared with group A, group B had shorter remission and a longer time to
      intractability during the first 5 years and more were intractable in the fifth
      year of follow-up. Sixteen other patients had a late onset of intractability
      after 5 years of follow-up, sometimes after long periods of remission (group C).
      No significant differences in baseline characteristics were found among groups A,
      B, and C, but slightly more children in groups B and C became mentally retarded
      during the follow-up. In all groups, antiepileptic drugs were of little use in
      preventing and ending intractability. SIGNIFICANCE: There is a large
      unpredictable variation in time of onset, course, and duration of intractability,
      with a higher chance of final intractability after a poor course during the first
      5 years of follow-up. The natural course of epilepsy probably best explains the
      variable course of intractability. The effect of medication seems to be minor.

PMID- 22417004
TI  - The structural relationships between organizational commitment, global job
      satisfaction, developmental experiences, work values, organizational support, and
      person-organization fit among nursing faculty.
AB  - GUTIERAIM: The aim of this correlational study was to examine the relations
      between organizational commitment, perceived organizational support, work values,
      person-organization fit, developmental experiences, and global job satisfaction
      among nursing faculty. BACKGROUND: The global nursing shortage is well
      documented. At least 57 countries have reported critical shortages. The lack of
      faculty is finally being recognized as a major issue directly influencing the
      ability to admit and graduate adequate numbers of nurses. As efforts increase to
      both recruit and retain faculty, the concept of organizational commitment and
      what it means to them is important to consider. DESIGN: A cross-sectional
      correlational design was used. METHODS: The present study investigated the
      underlying structure of various organizational factors using structural equation
      modelling. Data were collected from a stratified random sample of nurse faculty
      during the academic year 2006-2007. RESULTS: The final model demonstrated that
      perceived organizational support, developmental experiences, person-organization
      fit, and global job satisfaction positively predicted nurse faculty's
      organizational commitment to the academic organization. Cross-validation results
      indicated that the final full SEM is valid and reliable. CONCLUSIONS: Nursing
      faculty administrators able to use mentoring skills are well equipped to build
      positive relationships with nursing faculty, which in turn, can lead to increased
      organizational commitment, productivity, job satisfaction, and perceived
      organizational support, among others.

PMID- 22417005
TI  - Adaptive diffuse domain approach for calculating mechanically induced deformation
      of trabecular bone.
AB  - Remodelling of trabecular bone is essentially affected by the mechanical load of
      the trabeculae. Mathematical modelling and simulation of the remodelling process
      have to include time-consuming calculations of the displacement field within the
      complex trabecular structure under loading. We present an adaptive diffuse domain
      approach for calculating the elastic bone deformation based on micro computer
      tomogram data of real trabecular bone structures and compared it with a
      conventional voxel-based finite element method. In addition to allowing for
      higher computational efficiency, the adaptive approach is characterised by a very
      smooth representation of the bone surface, which suggests that this approach
      would be suitable as a basis for future simulations of bone resorption and
      formation processes within the trabecular structure. 

PMID- 22417006
TI  - Epidermal growth factor receptor copy number in potentially malignant oral
      disorders and oral squamous cell carcinoma: a short communication and preliminary
      study.
AB  - INTRODUCTION: This preliminary study compared the epidermal growth factor
      receptor (EGFR) copy number in patients with potentially malignant oral disorders
      (PMODs) and oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: Group 1
      comprised 20 patients with oral leukoplakia and group 2 comprised 19 cases of
      OSCC. We estimated the EGFR copy number in both groups using real-time reverse
      transcription polymerase chain reaction assays. We used laser microdissection
      (LMD) for EGFR amplification, and overexpression was performed. RESULTS:   The
      EGFR copy number was higher in group 2 (9.1 +/- 6.2) than in group 1 (3.8 +/-
      1.5). The greatest copy number was found in the non-homogeneous leukoplakias, but
      the difference in homogeneous cases was not significant (Mann-Whitney test,
      P>0.05). In group 2, the EGFR copy number was higher in advanced stages than in
      early stages, but again lacked statistical significance. CONCLUSIONS: The EGFR
      copy number may be a useful biomolecular marker to differentiate PMODs from OSCC.
      The EGFR was higher in non-homogeneous leukoplakias and in the advanced stages of
      OSCC.

PMID- 22417008
TI  - Alexis Carrel.

PMID- 22417007
TI  - MUC2 polymorphisms are associated with endometriosis development and infertility:
      a case-control study.
AB  - BACKGROUND: Mucins are highly glycosylated proteins protecting and lubricating
      epithelial surface of respiratory, gastrointestinal and reproductive tracts.
      Members of the mucin protein family have been suggested to play an important role
      in development of endometriosis and infertility. This study investigates genetic
      association of mucin2 (MUC2) with the risk of endometriosis and endometriosis
      related infertility. METHODS: This case-control study was conducted at China
      Medical University Hospital, with 195 endometriosis patients and 196 healthy
      controls enrolled. Genotyping of six SNPs (rs2856111, rs11245936, rs10794288,
      rs10902088, rs7103978 and rs11245954) within MUC2 gene were performed by using
      Taqman genotyping assay; individual SNP and haplotype associations with
      endometriosis and endometriosis-related infertility were assessed by chi2 test.
      RESULTS: Endometriosis patients exhibit significantly lower frequency of the
      rs10794288 C allele, the rs10902088 T allele and the rs7103978 G allele (P =
      0.030, 0.013 and 0.040, respectively). In addition, the rs10794288 C allele and
      the rs10902088 T allele were also less abundant in patients with infertility
      versus fertile ones (P = 0.015 and 0.024, respectively). Haplotype analysis of
      the endometriosis associated SNPs in MUC2 also showed significantly association
      between the most common haplotypes and endometriosis or endometriosis-related
      infertility. CONCLUSIONS: MUC2 polymorphisms, especially rs10794288 and
      rs10902088, are associated with endometriosis as well as endometriosis-related
      infertility. Our data present MUC2 as a new candidate involved in development of
      endometriosis and related infertility in Taiwanese Han women.

PMID- 22417009
TI  - Long-term after donation, who are the living kidney donors?*.

PMID- 22417010
TI  - Human T-cell leukemia virus type 1 infection worsens prognosis of hepatitis C
      virus-related living donor liver transplantation.
AB  - Severe and life-threatening donor-transmitted human T-cell leukemia virus type 1
      (HTLV-1) infections after solid organ transplantation have been reported.
      However, in HTLV-1-infected recipients, graft and patient survival were not fully
      evaluated. A total of 140 patients underwent living donor liver transplantation
      (LDLT). Of these, 47 of 126 adult recipients showed indications of hepatitis C
      virus (HCV)-related liver disease. The HTLV-1 prevalence rate was 10 of 140
      recipients (7.14%) and three of 140 donors (0.02%). In HCV-related LDLT, graft
      and patient survival was worsened by HTLV-1 infection in recipients (seven
      cases). The 1-, 3-, and 5-year survival rates in the HCV/HTLV-1-co-infected group
      were 67%, 32%, and 15%, respectively, and the corresponding rates in the HCV-mono
      infected group were 80%, 67%, and 67%, respectively. Only the 5-year survival
      rates were statistically significant (P=0.04, log-rank method). HTLV-1 infection
      in recipients is also an important factor in predicting survival in HTLV-1
      endemic areas.

PMID- 22417011
TI  - Immune thrombocytopenic purpura and Kaposi's sarcoma in a liver transplant
      recipient.

PMID- 22417012
TI  - An open-label phase I trial of a live attenuated H2N2 influenza virus vaccine in
      healthy adults.
AB  - BACKGROUND: Live attenuated influenza vaccines (LAIV) against a variety of
      strains of pandemic potential are being developed and tested. We describe the
      results of an open-label phase I trial of a live attenuated H2N2 virus vaccine.
      OBJECTIVES: To evaluate the safety, infectivity, and immunogenicity of a live
      attenuated H2N2 influenza virus vaccine. PARTICIPANTS/METHODS: The A/Ann
      Arbor/6/60 (H2N2) virus used in this study is the attenuated, cold-adapted,
      temperature-sensitive strain that provides the genetic backbone of seasonal LAIV
      (MedImmune). We evaluated the safety, infectivity, and immunogenicity of two
      doses of 10(7) TCID(50) of this vaccine administered by nasal spray 4 weeks apart
      to normal healthy seronegative adults. RESULTS: Twenty-one participants received
      a first dose of the vaccine; 18 participants received a second dose. No serious
      adverse events occurred during the trial. The most common adverse events after
      vaccination were headache and musculoskeletal pain. The vaccine was restricted in
      replication: 24% and 17% had virus detectable by culture or rRT-PCR after the
      first and second dose, respectively. Antibody responses to the vaccine were also
      restricted: 24% of participants developed an antibody response as measured by
      either hemagglutination-inhibition assay (10%), or ELISA for H2 HA-specific serum
      IgG (24%) or IgA (16%) after either one or two doses. None of the participants
      had a neutralizing antibody response. Vaccine-specific IgG-secreting cells as
      measured by enzyme-linked immunospot increased from a mean of 0.5 to 2.0/10(6)
      peripheral blood mononuclear cells (PBMCs); vaccine-specific IgA-secreting cells
      increased from 0.1 to 0.5/10(6) PBMCs. CONCLUSIONS: The live attenuated H2N2 1960
      AA ca vaccine demonstrated a safety profile consistent with seasonal trivalent
      LAIV but was restricted in replication and minimally immunogenic in healthy
      seronegative adults.

PMID- 22417014
TI  - Global oximetry -- an oximeter for every patient, every time.

PMID- 22417013
TI  - CXCR4 expression in feline mammary carcinoma cells: evidence of a proliferative
      role for the SDF-1/CXCR4 axis.
AB  - BACKGROUND: Mammary tumours frequently develop in female domestic cats being
      highly malignant in a large percentage of cases. Chemokines regulate many
      physiological and pathological processes including organogenesis, chemotaxis of
      inflammatory cells, as well as tumour progression and metastasization. In
      particular, the chemokine/receptor pair SDF-1/CXCR4 has been involved in the
      regulation of metastatic potential of neoplastic cells, including breast cancer.
      The aim of this study was the immunohistochemical defininition of the expression
      profile of CXCR4 in primary and metastatic feline mammary carcinomas and the
      evaluation of the role of SDF-1 in feline mammary tumour cell proliferation.
      RESULTS: A total of 45 mammary surgical samples, including 33 primary tumours (31
      carcinomas and 2 adenomas), 6 metastases, and 4 normal mammary tissues were
      anlyzed. Tumor samples were collected from a total number of 26 animals, as in
      some cases concurrent occurrence of neoplasm in more than one mammary gland was
      observed. Tissues were processed for standard histological examination, and all
      lesions were classified according to the World Health Organization criteria.
      CXCR4 expression in neoplastic cells was evaluated by immunohistochemistry. The
      level of CXCR4 immunoreactivity was semi-quantitatively estimated as CXCR4 score
      evaluating both the number of positive cells and the intensity of staining. Six
      primary, fibroblast-free primary cultures were obtained from fresh feline mammary
      carcinomas and characterized by immunofluorescence for CXCR4 and malignant
      mammary cell marker expression. SDF-1-dependent in vitro proliferative effects
      were also assayed. CXCR4 expression was observed in 29 out of 31 malignant
      tissues with a higher CXCR4 score observed in 4 out of 6 metastatic lesions than
      in the respective primary tumours. In 2 benign lesions analyzed, only the single
      basaloid adenoma showed a mild positive immunostaining against CXCR4. Normal
      tissue did not show CXCR4 immunoreactivity. CXCR4 score was statistically
      significantly associated with the histological features of the samples, showing
      an increase accordingly with the degree of neoplastic transformation (from normal
      tissue to metastatic lesions). Finally, in the primary cultures obtained from 6
      primary feline mammary carcinomas CXCR4 expression was detected in all cells and
      its activation by SDF-1 in vitro treatment caused a significant increase in the
      proliferation rate in 5 out of 6 tumours. CONCLUSIONS: These results indicate
      that malignant feline mammary tumours commonly express CXCR4, with a higher level
      in malignant tumours, and, in most of the cases analysed, metastatic cells
      display stronger immunoreactivity for CXCR4 than the corresponding primary
      tumours. Moreover, CXCR4 activation in primary cultures of feline mammary
      carcinomas causes increase in the proliferative rate. Thus, SDF-1/CXCR4 system
      seems to play a tumorigenic in feline mammary gland malignancy and in vitro
      cultures from these tumour samples may represent an experimental model to
      investigate the biological and pharmacological role of this chemokinergic axis.

PMID- 22417015
TI  - Sugammadex: restricted vs unrestricted or selective vs non-selective?

PMID- 22417016
TI  - Histamine-releasing and allergenic properties of opioid analgesic drugs:
      resolving the two.
AB  - Opioid analgesics are amongst the most commonly administered drugs in hospitals.
      Whether natural or synthetic, they show some common structural features, morphine
      like pharmacological action and binding specificity for complementary opioid
      receptors. Tramadol differs from the other opioid analgesics in possessing
      monoaminergic activity in addition to its affinity for the u opioid receptor.
      Many opioids are potent histamine releasers producing a variety of haemodynamic
      changes and anaphylactoid reactions, but the relationship of the appearance of
      these effects to the histamine plasma concentration is complex and there is no
      direct and invariable relationship between the two. Studies of the histamine
      releasing effects, chiefly centred on morphine, reveal variable findings and
      conclusions often due to a range of factors including differences in technical
      measurements, dose, mode of administration, site of injection, the anatomical
      distribution of histamine receptors and heterogeneity of patient responses.
      Morphine itself has multiple direct effects on the vasculature and other
      haemodynamically-active mediators released along with histamine contribute to the
      variable responses to opioid drug administration. Despite their heavy use and
      occasional apparent anaphylactic-like side-effects, immunoglobulin E antibody
      mediated immediate hypersensitivity reactions to the drugs are not often
      encountered. Uncertainties associated with skin testing with these known
      histamine-releasers, and the general unavailability of opioid drug-specific
      immunoglobulin E antibody tests contribute to the frequent failure to adequately
      investigate and establish underlying mechanisms of reactions by distinguishing
      anaphylactoid from true anaphylactic reactions. Clinical implications for
      diagnosis of reactions and some speculations on the rarity of true Type 1
      allergies to these drugs are presented.

PMID- 22417017
TI  - Respiratory dysfunction in ventilated patients: can inspiratory muscle training
      help?
AB  - Respiratory muscle dysfunction is associated with prolonged and difficult weaning
      from mechanical ventilation. This dysfunction in ventilator-dependent patients is
      multifactorial: there is evidence that inspiratory muscle weakness is partially
      explained by disuse atrophy secondary to ventilation, and positive end-expiratory
      pressure can further reduce muscle strength by negatively shifting the length
      tension curve of the diaphragm. Polyneuropathy is also likely to contribute to
      apparent muscle weakness in critically ill patients, and nutritional and
      pharmaceutical effects may further compound muscle weakness. Moreover,
      psychological influences, including anxiety, may contribute to difficulty in
      weaning. There is recent evidence that inspiratory muscle training is safe and
      feasible in selected ventilator-dependent patients, and that this training can
      reduce the weaning period and improve overall weaning success rates.
      Extrapolating from evidence in sports medicine, as well as the known effects of
      inspiratory muscle training in chronic lung disease, a theoretical model is
      proposed to describe how inspiratory muscle training enhances weaning and
      recovery from mechanical ventilation. Possible mechanisms include increased
      protein synthesis (both Type 1 and Type 2 muscle fibres), enhanced limb perfusion
      via dampening of a sympathetically-mediated metaboreflex, reduced lactate levels
      and modulation of the perception of exertion, resulting in less dyspnoea and
      enhanced exercise capacity.

PMID- 22417018
TI  - Systematic review of oxytocin dosing at caesarean section.
AB  - We undertook a systematic review to determine the optimal dose of oxytocin after
      elective caesarean section or caesarean section in labouring women. We identified
      seven trials. These trials raise questions about the use of high dose (10
      international units; IU) or moderate dose (5 IU) oxytocin in both settings and
      provide evidence that lower doses are equally effective but associated with
      significantly fewer side-effects. For elective caesarean section, a slow 0.3 to 1
      IU bolus of oxytocin over one minute, followed by an infusion of 5 to 10 IU.h(-1)
      for four hours represents an evidence-based approach to dosing for women at low
      risk of postpartum haemorrhage. For the labouring parturient a slow 3 IU bolus of
      oxytocin, followed by an infusion of 5 to 10 IU.h(-1) for four hours is supported
      by limited evidence. These doses represent a starting point in the control of
      postpartum haemorrhage after caesarean section and do not reduce the need for
      mandatory active observation of the clinical situation, to detect situations that
      require additional doses of oxytocin or other uterotonic drugs. These doses of
      oxytocin minimise the risk of adverse haemodynamic changes as well as the
      unpleasant side-effect of nausea.

PMID- 22417019
TI  - Prevention of gastrointestinal bleeding due to stress ulceration: a review of
      current literature.
AB  - Our objective was to audit our current stress ulcer prophylaxis protocol (routine
      prescription of ranitidine and early enteral feeding) by identifying whether
      routine prescription of histamine-2 receptor antagonists or proton pump
      inhibitors as prophylaxis against stress-related mucosal disease and subsequent
      upper gastrointestinal bleeding is supported in the literature. We also aimed to
      ascertain what literature evidence supports the role of early enteral feeding as
      an adjunctive prophylactic therapy, as well as to search for burn-patient
      specific evidence, since burn patients are at high risk for developing this
      condition, with the aim of changing our practice. PubMed and Cochrane databases
      were searched for relevant articles, yielding seven randomised controlled trials
      comparing histamine-2 receptor antagonists and proton pump inhibitors in the
      prevention of upper gastrointestinal bleeding associated with stress-related
      mucosal disease and three separate meta-analyses. Despite level 1 clinical
      evidence, no significant difference in efficacy between histamine-2 receptor
      antagonists and proton pump inhibitor treatment groups was demonstrated. No
      significant difference was demonstrated in the incidence of nosocomial pneumonia
      between the two drugs given in this indication. However, enteral feeding was
      found to be safe and effective in preventing clinically significant upper
      gastrointestinal bleeding. Patients able to tolerate feeds demonstrated no
      additional benefit with concomitant pharmacological prophylactic therapy. Since
      all burn patients at the Royal Adelaide Hospital are fed from very early in their
      admission, the literature suggests that we, like our intensive care unit
      colleagues, should abolish our reliance on pharmacological prophylaxis, the
      routine prescription of which is not supported by the evidence.

PMID- 22417020
TI  - Comparison of outcomes by modality for critically ill patients requiring renal
      replacement therapy: a single-centre cohort study adjusting for time-varying
      illness severity and modality exposure.
AB  - Prolonged intermittent renal replacement therapy (PIRRT) is a recently defined
      acute modality for critically ill patients, and in theory combines the superior
      detoxification and haemodynamic stability of continuous renal replacement therapy
      (CRRT) with the operational convenience and low cost of intermittent
      haemodialysis (iHD). We performed a retrospective cohort study for all critically
      ill adults treated with renal replacement therapy at our centre in Auckland, New
      Zealand from 1 January 2002 to 31 December 2008. The exposure of interest was
      modality (PIRRT, CRRT, iHD). Primary and secondary outcomes were patient
      mortality determined at hospital discharge and 90 days post renal replacement
      therapy inception, respectively. Co-variates included co-morbidity and baseline
      illness severity measured by Acute Physiology and Chronic Health Evaluation IV
      and Sepsis-Related Organ Failure Assessment (SOFA) and time-varying illness
      severity measured by daily SOFA scores. We used Marginal Structural Modelling to
      estimate mortality risk adjusting for both time-varying illness severity and
      modality exposure. A total of 146 patients with 633 treatment-days had sufficient
      data for modelling. With PIRRT as the reference, the adjusted hazard ratios for
      patient hospital mortality were 1.31 (0.60 to 2.90) for CRRT and 1.22 (0.21 to
      2.29) for iHD. Corresponding estimates for mortality at 90 days were 0.96 (0.39
      to 2.36) and 2.22 (0.49 to 10.11), respectively, reflecting the poorer longer
      term prognosis of patients still on iHD at hospital discharge with delayed or non
      recovery of acute kidney injury. Our study supports the recent increased use of
      PIRRT, which within limits can be regarded as safe and effective.

PMID- 22417021
TI  - Pharmacokinetics of oxycodone after subcutaneous administration in a critically
      ill population compared with a healthy cohort.
AB  - This study aimed to characterise and compare the absorption pharmacokinetics of a
      single subcutaneous dose of oxycodone in critically ill patients and healthy
      subjects. Blood samples taken at intervals from two minutes to eight hours after
      a subcutaneous dose of oxycodone in patients (5 mg) and healthy volunteers (10
      mg) were assayed using high performance liquid chromatography. Data were analysed
      using a non-compartmental approach and presented as mean (SD). Parameters were
      corrected for dose differences between the groups assuming linear kinetics. Ten
      patients (eight male, two female) and seven healthy male subjects were included.
      Maximum venous concentration and area under the concentration curve were
      approximately two-fold lower in the patient group for an equivalent dose,
      suggesting either reduced bioavailability or increased clearance: maximum venous
      concentration 0.14 +/- 0.06 vs 0.05 +/- 0.02 ug/ml (P <0.0001); area under the
      concentration curve 19.50 +/- 9.15 vs 9.72 +/- 2.71 ug/ml/minute (P <0.001)
      respectively. However, time to maximum venous concentration and mean residence
      time were not different, suggesting similar absorption rates: time to maximum
      venous concentration 22.10 +/- 18.0 vs 20.50 +/- 16.10 minutes (P=0.81); mean
      residence time 353 +/- 191 vs 291 +/- 80 minutes (P=0.26). Kinetic parameters
      were less variable in patients than in volunteers. The patients therefore had
      reduced exposure to subcutaneous oxycodone. This warrants further model-based
      analysis and experimentation. Dose regimens for subcutaneous oxycodone developed
      in healthy volunteers cannot be directly translated to critically ill patients.

PMID- 22417022
TI  - An observational study exploring amplitude-integrated electroencephalogram and
      spectral edge frequency during paediatric anaesthesia.
AB  - Processed electroencephalography is used in adults to guide anaesthesia, but the
      algorithms used may not apply to infants. Knowledge of infants'
      electroencephalogram (EEG) responses to anaesthetics is fragmentary. An earlier
      pilot study suggested amplitude-integrated EEG (aEEG) may be a useful measure of
      anaesthetic effect. The aim of this study was to determine how aEEG changes
      between awake and anaesthetised children of varying ages and to compare the
      response to that seen with Spectral Edge Frequency 90% (SEF90). A prospective
      observational study of children receiving a general anaesthetic was conducted.
      Anaesthetic regimen remained at the discretion of the treating anaesthetist. EEG
      data were collected using the BrainZ ReBrim(TM) monitor using forehead and
      biparietal montages. SEF90 and aEEG were compared across age groups, EEG montage
      and between awake and anaesthetised states. A total of 178 children (aged 24 days
      to 14 years) were recruited. All aEEGs were greater during anaesthesia compared
      to when awake and this difference varied with age. Only children older than two
      years showed lower SEF90 while anaesthetised compared to when awake. SEF90 from
      children younger than six months was higher during anaesthesia compared to when
      awake. Analysis of parietal and forehead EEG montages revealed age-related
      differences. These findings suggest that SEF90 and aEEG can discriminate between
      awake and anaesthetised states in older children. In younger children aEEG
      changes are less pronounced and SEF90 either cannot discriminate between states
      or responds paradoxically. The aEEG may be marginally better than other EEG
      parameters in measuring anaesthetic depth in children.

PMID- 22417023
TI  - Performance of the PIRO score for predicting mortality in patients with
      ventilator-associated pneumonia.
AB  - The ventilator-associated pneumonia (VAP) PIRO score is a new scoring system
      based on the PIRO concept. The aim of this study was to validate the PIRO score
      against the Acute Physiology and Chronic Health Evaluation (APACHE) II and VAP
      APACHE II in an independent group of VAP patients. Areas under the receiver
      operating characteristic curves were compared to determine the tests' abilities
      to predict intensive care unit and 28-day mortality. Variables associated with
      intensive care unit mortality were evaluated. One hundred and forty-eight
      intensive care unit patients who met radiographic and clinical criteria for VAP
      were included. The area under the receiver operating characteristic curves for
      predicting intensive care unit mortality with the PIRO, APACHE II and VAP APACHE
      II scores were 0.605 (P=0.03), 0.631 (P=0.01) and 0.724 (P <0.0001),
      respectively. Areas under the receiver operating characteristic curve for
      predicting 28-day mortality were 0.614 (P=0.01) for PIRO, 0.633 (P=0.01) for
      APACHE II and 0.697 (P=0.002) for VAP APACHE II. No differences in area under the
      receiver operating characteristic curve between scores were found at either
      endpoint. Variables independently associated with intensive care unit mortality
      were bacteraemia (adjusted odds ratio 7.16, 95% confidence interval 1.19 to
      42.98, P=0.03) and APACHE II (1.06, 1.01 to 1.11, P=0.006). VAP PIRO score was
      not a good predictor of intensive care unit and 28-day mortality. The low
      sensitivity and specificity of VAP PIRO score preclude its use clinically.

PMID- 22417024
TI  - Lignocaine plasma levels following topical gel application in laparoscopic and
      hysteroscopic procedures.
AB  - The study aim was to determine plasma lignocaine concentrations resulting from
      topical application of a newly formulated, sterile two-pack lignocaine gel in
      laparoscopic and hysteroscopic procedures. This was an open label single-centre
      study in which six female patients underwent laparoscopy and six underwent
      hysteroscopy. One venous blood sample was extracted pre-gel application, followed
      by 10 samples over a 24 hour period following application. Samples were
      centrifuged, stored at -20 degrees C and subsequently analysed for lignocaine and
      its metabolite, monoethyl-glycinexylidide. Application of gel in doses between
      2.7 and 5.8 mg/kg of lignocaine resulted in a maximum plasma concentration in any
      patient of 1520 ng/ml lignocaine and 240 ng/ml monoethyl-glycinexylidide. These
      maximum concentrations were recorded in a patient undergoing a laparoscopic
      procedure and patients undergoing hysteroscopic procedures all recorded lower
      maximum concentrations compared with patients undergoing laparoscopy; the maximum
      observed concentrations in a patient having a hysteroscopy were 420 ng/ml
      lignocaine and 56 ng/ml of monoethyl-glycinexylidide.A new sterile two-pack
      topical lignocaine gel, applied at the end of laparoscopic and hysteroscopic
      procedures in doses up to 5.84 mg/kg, resulted in plasma lignocaine levels below
      those known to have the potential to cause central nervous system toxicity.

PMID- 22417025
TI  - An analysis of computer-assisted pre-screening prior to elective surgery.
AB  - In order to assess the potential utility of guided patient self-assessment as an
      early preoperative triage tool, a computer-assisted questionnaire delivered by a
      non-clinician via telephone was 1) compared to face-to-face interview and
      examination by anaesthetists in outpatient clinics and 2) evaluated as a
      mechanism to stream patients to day of surgery assessment. In total, 514 patients
      scheduled for elective surgery in two tertiary public hospitals were assessed
      initially by telephone and then in an outpatient clinic. Both forms of assessment
      were marked by panels of specialist anaesthetists, who also provided an opinion
      on which patients would have been suitable to bypass preoperative anaesthetic
      outpatient assessment based upon information provided by the telephone interview.
      Overall, the quality of assessment provided by non-clinician telephone interview
      was comparable to face-to-face interview by anaesthetists, although more complex
      issues required face-to-face assessment. Panel review considered that 398
      patients (60%) would not have required evaluation by an anaesthetist until the
      day of surgery, thus avoiding the need to separately attend a preoperative
      outpatient clinic. The sensitivity of telephone interview provided information to
      correctly classify patients as suitable for day of surgery evaluation was 98%
      (95% confidence interval 96 to 99%) with a specificity of 97% (95% confidence
      interval 92 to 98%). This study demonstrates that remote computer-assisted
      assessment can produce quality patient health information and enable early
      patient work-up and triage with the potential to reduce costs through more
      efficient use of resources.

PMID- 22417026
TI  - Ketofol (mixture of ketamine and propofol) administration in electroconvulsive
      therapy.
AB  - The aim of this study was to evaluate the effect of a ketamine:propofol
      combination ('ketofol') for electroconvulsive therapy on seizure activity,
      haemodynamic response and recovery parameters, and to compare with these with the
      effects of propofol alone. Twenty-four patients underwent a total of 144
      electroconvulsive therapy sessions, allocated in this prospective, double-blind,
      crossover study. Patients were randomly assigned to receive 1 mg/kg ketofol (0.5
      mg/kg propofol plus 0.5 mg/kg ketamine) or 1 mg/kg propofol 1% for anaesthesia
      induction. Seizure duration and quality, haemodynamic data, recovery parameters
      and side-effects were recorded and analysed between groups. Both motor and
      electroencephalography seizure durations in the ketofol group (29 +/- 17 and 41
      +/- 17 seconds, respectively) were similar to that in the propofol group (28 +/-
      13 and 38 +/- 16 seconds, respectively). Postictal suppression index was higher
      in the ketofol group (89.63 +/- 7.88) than in the propofol group (79.74 +/- 14.6)
      (P <0.05). In the ketofol group, heart rate after the seizure ended and mean
      arterial pressures, recorded at 0 and 5 minutes after the seizure ended, were
      higher than in the propofol group. Time to obeying commands was longer in the
      ketofol group (P <0.05). There were no untoward psychological reactions following
      ketofol. Although no superiority to propofol in terms of seizure duration,
      haemodynamic or recovery parameters was found, the ketofol mixture selected in
      our study provided better seizure quality than propofol. We conclude that ketofol
      can be an alternative strategy to enhance the seizure quality and clinical
      efficiency of electroconvulsive therapy.

PMID- 22417027
TI  - Evaluation of the Mediseus epidural simulator.
AB  - The demand for increased patient safety has led to greater use of simulation
      training of health professionals performing medical procedures. The study aim was
      to evaluate the usefulness of the Mediseus(r) Epidural Simulator in teaching
      basic epidural needle-handling skills. Three groups of 15 anaesthetists
      (Novice=zero to two year anaesthesia trainees; Intermediate=three- to five-year
      anaesthesia trainees; Expert=consultants and regional-specialist anaesthetists)
      from three different medical centres participated. Each participant performed 20
      simulated epidural needle insertions and was scored on several parameters (e.g.
      time, success of the insertion, bone collisions). Following familiarisation with
      the simulator and the needle insertions, participants answered seven questions on
      the applicability of the simulator to the teaching of basic epidural needle
      handling skills. There was a clear learning effect with regard to the simulation
      procedure time, this decreasing throughout the experiment (P=0.037). There was no
      significant influence of either group or experience with the simulator in the
      study on the number or type of errors made. The quality of the simulation was
      scored 2.3 out of 5.0 (for bone simulation) and 4.7 (for loss-of-resistance
      simulation). All groups considered that the simulator was best suited for
      training prospective anaesthetists. Each group rated the usefulness of the
      simulator for training novices at greater than 3.0 out of 5.0. The Mediseus(r)
      Epidural Simulator seems to be an appropriate training device for an introduction
      to epidural needle insertion. For medical professionals with procedural
      knowledge, the simulation is not realistic enough and the simulator did not
      distinguish between the groups based on the errors made.

PMID- 22417028
TI  - Beta-blocker management in high-risk patients presenting for non-cardiac surgery:
      before and after the POISE Trial.
AB  - The POISE Trial was a randomised, placebo-controlled, double-blind study of the
      effectiveness of perioperative beta-blockade in preventing cardiac events
      including death in 8351 patients. Our hypothesis was that knowledge of the
      results of the POISE Trial would either increase or decrease the use of effective
      perioperative beta-blockade, depending on the result. Patients presenting for non
      cardiac surgery and at risk of perioperative cardiac events were recruited in two
      cohorts before and after the release of the POISE Trial results. Effective
      perioperative beta-blockade was defined as heart rate <65 beats per minute for at
      least 80% of the perioperative period in patients prescribed beta-blockers.
      Effective perioperative beta-blockade was achieved in 22 (11.5%) of 191 patients
      prescribed perioperative beta-blockade in the first cohort (n=392) and seven (6%)
      of 118 patients in the second cohort (n=241) (P=0.10). Effective heart rate
      control was achieved in 29 (9%) patients prescribed perioperative beta-blockers
      compared with 10 (3%) patients not prescribed perioperative beta-blockers
      (P=0.001). The rate of implementation of effective beta-blockade was low before
      POISE and this did not change significantly after publication. Our finding does
      not provide reliable evidence of a change in practice as a result of the POISE
      Trial.

PMID- 22417029
TI  - Rural anaesthetic audit 2006 to 2010.
AB  - In order to review anaesthetic morbidity in our remote rural hospital, a
      retrospective audit of all anaesthetic records was undertaken for a five-year
      period between 2006 and 2010. Eight hundred and eighty-nine anaesthetic records
      were reviewed. The patients were all American Society of Anaesthesiologists
      physical status I to III. Ninety-eight percent of the anaesthetics were performed
      by general practitioner (non-specialist) anaesthetists. There were no anaesthetic
      deaths or serious adverse outcomes reported over this period. Sixteen
      intraoperative and seven postoperative problems were documented, but all were
      resolved uneventfully. The most common problems documented were difficult
      intubation (n=9) and respiratory depression (n=3). Within the limitations of this
      retrospective audit, these findings indicate that general practitioner
      anaesthetists provided safe anaesthesia in a remote rural hospital. It is our
      opinion that the case selection, prior experience of anaesthetic and theatre
      staff, stable nursing workforce and the use of protocols were important factors
      in determining the low rate of adverse events. However, we caution against over
      interpretation of the data, given its retrospective nature, relatively small
      sample size, reliance on case records and the absence of agreed definitions for
      adverse events. We would also like to encourage all anaesthetic services, however
      remote, to audit their results as part of ongoing quality assurance.

PMID- 22417030
TI  - The influence of unrestricted use of sugammadex on clinical anaesthetic practice
      in a tertiary teaching hospital.
AB  - This retrospective casenote audit involving 374 patients requiring intubation for
      an anaesthetic found that when the availability of sugammadex became
      unrestricted, its use increased from 7.1 to 65.3% (P <0.0001) of all muscle
      relaxant reversals, while neostigmine use decreased from 59.6 to 12.5%.
      Rocuronium use decreased slightly (90.8 to 79.2%, P=0.006) but vecuronium use
      increased (2.1 to 8.3%, P=0.02). Cisatracurium and suxamethonium use were
      unchanged. Total rocuronium dose (55.9 +/- 24.1 vs 60.4 +/- 22.3 mg) and the
      number of doses (1.9 +/- 1.48 to 1.96 +/- 1.27) were unchanged, but the time
      between the last dose and reversal decreased (91.7 +/- 68.1 to 62 +/- 52.4
      minutes, P=0.0002). There appeared to be no change in postoperative nausea and
      vomiting, or post-anaesthesia care unit time or oxygen saturation levels.
      Anaesthetic theatre time fell from 143.5 +/- 85.8 to 120 +/- 71.2 minutes
      (P=0.01) and remained significant when adjusted for confounding variables (ratio
      of means 1.17, 95% confidence interval 1.03 to 1.34, P=0.02), although inferences
      in relation to causality are limited by the retrospective and observational
      design of the study. Hospital stay also appeared to fall (4.2 +/- 3.5 to 3.4 +/-
      3.0 days, P=0.035), but was not statistically significant when adjusted for
      confounding variables (ratio of means 1.04, 95% confidence interval 0.89 to 1.2,
      P=0.59). These observations suggest that the unrestricted availability of
      sugammadex will change how steroid-based neuromuscular blocking drugs are used
      and reversed, but further research is needed to determine if patient outcomes
      will improve.

PMID- 22417031
TI  - Unrestricted access to sugammadex: impact on neuromuscular blocking agent choice,
      reversal practice and associated healthcare costs.
AB  - Sugammadex is known to rapidly and completely reverse the effects of amino
      steroidal neuromuscular blocking agents. However, the high costs of sugammadex
      have so far prevented its introduction as the standard reversal agent in most
      healthcare systems. At the Royal Perth Hospital, sugammadex was recently
      introduced as an unrestricted alternative to neostigmine for the reversal of
      amino-steroidal neuromuscular blocking agents. The aim of this retrospective
      observational audit was to investigate the impact of this change on clinical
      practice and associated healthcare costs. Data from all patients intubated during
      a one-month period in April to May 2010 and for a similar period in 2011 were
      retrospectively collected and the use of neuromuscular blocking agents and
      reversal agents were identified and the associated costs were calculated. More
      steroidal neuromuscular blocking agents and sugammadex (+743%), but less
      glycopyrrolate and neostigmine (-48%) were used in 2011. Using the manufacturer's
      list price, muscle relaxation and reversal costs increased from about A$42 per
      case to about A$127 per case. Between the investigated time periods no
      differences were found for anaesthesia time, operating time or time spent in the
      post anaesthesia care unit. However, there was a statistically significant
      decrease in the time between surgery and discharge (median 2.0 vs 2.2 days).
      While the design of the audit was such that no inferences can be made about the
      cause of this change, this is an interesting observation worthy of further
      investigation.

PMID- 22417032
TI  - A persistent 'can't intubate, can't oxygenate' crisis despite rocuronium reversal
      with sugammadex.
AB  - A 'can't intubate, can't oxygenate' airway crisis is a rare event which most
      anaesthetists will never experience during their career(1,2). This report
      highlights the outcome of time-critical decisions in a potential airway
      catastrophe. Rocuronium was used as an alternative muscle relaxant for rapid
      sequence induction. The use of sugammadex in 'can't intubate, can't oxygenate'
      crises is discussed and highlights how, despite adequate reversal of
      neuromuscular blockade, the 'can't intubate, can't oxygenate' situation failed to
      resolve. An asymptomatic vallecular cyst was the causal factor in this scenario.
      Anaesthetic issues surrounding this pathology are discussed.

PMID- 22417033
TI  - Postpartum seizure and ischaemic stroke following dural puncture and epidural
      blood patch.
AB  - A 33-year-old parturient experienced seizures, then an ischaemic stroke after
      caesarean section, while undergoing an epidural blood patch for dural puncture. A
      diagnosis of normotensive late postpartum eclampsia, with either a posterior
      reversible encephalopathy syndrome or postpartum vasculopathy, leading to stroke,
      was made - based primarily on a temporal relationship to the postpartum period
      and consistent findings on magnetic resonance imaging and angiography scans and
      an electroencephalogram. The difficulties in definitively elucidating the cause
      of seizures and cerebral infarction in the postpartum period and the impact of
      anaesthetic interventions in this case are discussed.

PMID- 22417037
TI  - Normal rocuronium sensitivity after titrated intraoperative sugammadex.

PMID- 22417038
TI  - Dramatic improvement in oxygenation after sternotomy in a patient with acute
      respiratory distress syndrome.

PMID- 22417039
TI  - Dexmedetomidine for the treatment of severe postoperative functional stridor.

PMID- 22417040
TI  - Postoperative occipital nerve injury in a child.

PMID- 22417041
TI  - A medical student with malignant hyperthermia susceptibility.

PMID- 22417042
TI  - Fracture of reusable ProSealTM laryngeal mask airway after excessive use.

PMID- 22417043
TI  - Patient perceptions of anaesthesia research priorities -- a failed study.

PMID- 22417044
TI  - Strategies for the withdrawal of extracorporeal membrane oxygenation for severe
      acute respiratory failure support: a new challenge?

PMID- 22417045
TI  - Long-term betel nut chewing is not a predictor of difficult tracheal intubation.

PMID- 22417046
TI  - Acute respiratory failure from pulmonary tuberculosis due to head trauma
      immunosupression.

PMID- 22417047
TI  - Amitraz poisoning -- familiar presentation, unfamiliar diagnosis.

PMID- 22417048
TI  - Transilluminated ProSealTM laryngeal mask airway insertion.

PMID- 22417049
TI  - A patient with clove oil intoxication.

PMID- 22417050
TI  - Importance of securing central venous catheters.

PMID- 22417051
TI  - Rhizopus microsporus infection in an immunocompetent host: a case of
      immunoparalysis?

PMID- 22417052
TI  - False-negative anti-treponemal immunohistochemistry in secondary syphilis.
AB  - BACKGROUND: While serological studies are the primary tool used to confirm the
      diagnosis of secondary syphilis, skin biopsies are often performed to control for
      potential false positives and negatives. Immunohistochemistry using anti-T.
      pallidum specific antibodies has proven to have a very high sensitivity and
      specificity for identification of spirochetes in biopsy specimens, but can
      occasionally fail to identify organisms in clinically and serologically confirmed
      cases. METHODS: We report two cases of apparently negative biopsy specimens in
      which rare organisms were subsequently identified by detailed study of multiple
      additional sections. RESULTS: Our experience suggests that the sensitivity of
      immunohistochemistry for syphilitic spirochetes may be improved by repeat
      immunostaining.

PMID- 22417053
TI  - Russian wheat aphids (Diuraphis noxia) in China: native range expansion or recent
      introduction?
AB  - In this study, we explore the population genetics of the Russian wheat aphid
      (RWA) (Diuraphis noxia), one of the world's most invasive agricultural pests, in
      north-western China. We have analysed the data of 10 microsatellite loci and
      mitochondrial sequences from 27 populations sampled over 2 years in China. The
      results confirm that the RWAs are holocyclic in China with high genetic diversity
      indicating widespread sexual reproduction. Distinct differences in microsatellite
      genetic diversity and distribution revealed clear geographic isolation between
      RWA populations in northern and southern Xinjiang, China, with gene flow
      interrupted across extensive desert regions. Despite frequent grain
      transportation from north to south in this region, little evidence for RWA
      translocation as a result of human agricultural activities was found.
      Consequently, frequent gene flow among northern populations most likely resulted
      from natural dispersal, potentially facilitated by wind currents. We also found
      evidence for the long-term existence and expansion of RWAs in China, despite
      local opinion that it is an exotic species only present in China since 1975. Our
      estimated date of RWA expansion throughout China coincides with the debut of
      wheat domestication and cultivation practices in western Asia in the Holocene. We
      conclude that western China represents the limit of the far eastern native range
      of this species. This study is the most comprehensive molecular genetic
      investigation of the RWA in its native range undertaken to date and provides
      valuable insights into the history of the association of this aphid with
      domesticated cereals and wild grasses.

PMID- 22417054
TI  - How citrate ligands affect nanoparticle adsorption to microparticle supports.
AB  - Residual ligands from colloidal synthesis of nanoparticles influence adsorption
      of nanoparticles to supports and may complicate fabrication of nanoparticle
      decorated microparticles. In this work, we studied the adsorption of completely
      ligand-free metal nanoparticles and controlled ligand-functionalized
      nanoparticles to chemically inert microparticle supports. Adsorption of ligand
      free silver nanoparticles to barium sulfate microparticle supports is a
      quantitative, nonreversible process following Freundlich adsorption isotherm.
      However, adsorption efficiency is very sensitive to ligand concentration applied
      during laser-based synthesis of silver nanoparticles: exceeding a specific
      threshold concentration of 50 MUmol/L citrate equal to a nanoparticle ligand
      surface coverage of about 50%, results in an almost complete prevention of
      nanoparticle adsorption because of electrosteric repulsion by ligand shell. Laser
      based synthesis of nanoparticle-decorated microparticles is demonstrated with a
      variety of metal nanoparticles (Ag, Au, Pt, Fe) and supporting microparticles
      (calcium phosphate, titanium dioxide, barium sulfate) with application potential
      in heterogeneous catalysis or biomedicine where ligand control offers extra
      value, like enhanced catalytic activity or biocompatibility.

PMID- 22417055
TI  - Renal recipients' educational experiences in the early post-operative phase--a
      qualitative study.
AB  - Renal recipients need to acquire significant amount of knowledge for their life
      post-transplantation. More knowledge on kidney recipients' experiences after
      transplantation with regard to the patient education provided is needed. Sixteen
      renal recipients were interviewed 4-6 weeks post-transplantation about content
      and methods in the patient education programme. Data were analysed in the
      hermeneutic tradition. The patients experienced barriers towards learning in the
      early post-operative phase. Kidney transplantation was expressed as a 'turning
      point in life', causing learning difficulties because of both physical and mental
      stress. Survival knowledge was the label for topics concerning medication and
      rejection as they were experienced as essential for life. Situational knowledge,
      that is, knowledge related to recipients' individual life situations, requires
      further details in the main topics provided. The difference between knowing and
      practising what was taught was experienced as troublesome. The recipients
      expressed that a supportive learning atmosphere characterized by patience,
      respect, continuity and active participation was essential. This study revealed
      new knowledge about renal recipients' need for individual application of the
      educational content, as well as cognitive difficulties, and other factors
      impacting on learning in the early post-operative phase. The patients'
      perspective is an important and useful aid in creating effective interventions in
      this field.

PMID- 22417056
TI  - An infantile splenic hemangiopericytoma case treated with partial splenectomy.
AB  - Splenic hemangiopericytoma is a very rare tumor. So far only 10 patients (9
      adults, 1 child) have been reported in the literature and all of them were
      treated with total splenectomy. Herein, we report the first infant case of the
      splenic hemangiopericytoma in a 10-month-old girl and the first case that was
      treated with partial splenectomy for splenic hemangiopericytoma.

PMID- 22417057
TI  - Dosimetric comparison of robotic and conventional linac-based stereotactic lung
      irradiation in early-stage lung cancer.
AB  - We aimed to compare dosimetric characteristics of conventional linear accerator
      based treatment plans to those created using the robotic CyberKnife(r) (CK)
      treatment planning system for patients with early-stage lung cancer. Eight early
      stage lung cancer patients treated with stereotactic body radiotherapy (SBRT)
      using a conventional linac-based (LIN) system were included in this study. New
      treatment plans were created for the patients with the CK treatment planning
      system in order to compare the two platforms' dosimetric characteristics.
      Planning computed tomographies (CT) were obtained in three phases: free
      breathing, full exhalation and inhalation. The three GTVs were then added
      together for internal target volume (ITV) with LIN, whereas no ITV was used for
      CK. Planning target volumes (PTV) were constituted by adding 5-mm margin to GTV
      and ITV. Treatment plan was 54 Gy in three fractions. Five-field, seven-field,
      and dynamic-conformal arc planning techniques were used in LIN plans. Plans were
      compared according to dose heterogenity (D(max)-maximum dose), volume of 54 Gy
      (V54) and 27 Gy isodose (V27), conformity index (CI(54) and CI(27)) and lung
      volumes. PTVs were significantly smaller in CK plans (p=0.012). D(max) was
      significantly lower in ARC plans (p=0.01). Among all plans, CK had significantly
      tightest isodose shell received 54 Gy and 27 Gy (p=0.0001). Among LIN plans, V54
      was significantly (p=0.03) smaller in ARC plans; but no difference was observed
      for V27 values. LIN plans have better plan quality (CI(27) and CI(54)) than CK.
      No statistically significant difference was observed for lung volumes. CK plans
      had superior V54 and V27 values compared to LIN plans due to smaller PTV. LIN
      plans had better CI(27) and CI(54) values. Advantages of LIN treatment were no
      neccessity for fiducial marker use, which may cause pneumothorax, and
      significantly shorter beam-on treatment times. Both CK and LIN methods are
      suitable for lung SBRT.

PMID- 22417058
TI  - Effectiveness of virtual reality simulation software in radiotherapy treatment
      planning involving non-coplanar beams with partial breast irradiation as a model.
AB  - Virtual reality simulation software (VRS - FocalSim Version 4.40 with VRS
      prototype, Computerized Medical Systems, St. Louis, MO) is a new radiation dose
      planning tool that allows for 3D visualization of the patient and the machine
      couch (treatment table) in relationship to the linear accelerator. This allows
      the radiation treatment planner to have a "room's-eye-view" and enhances the
      process of virtual simulation. The aim of this study was to compare VRS to a
      standard planning program (XiO - Version 4.50, Computerized Medical Systems, St.
      Louis, MO) in regards to the time it took to use each program, the angles chosen
      in each, and to determine if there was a dosimetric benefit to using VRS. Ten
      patients who had undergone left-sided lumpectomies were chosen to have treatment
      plans generated. A partial breast irradiation (PBI) treatment plan by external
      beam radiation therapy (EBRT) was generated for each patient using two different
      methods. In the first method the full plan was generated using XiO software. In
      the second method beam angles were chosen using the VRS software, those angles
      were transferred to XiO, and the remaining part of the plan was completed using
      XiO (since VRS does not allow dose calculations). On average, using VRS to choose
      angles took about 10 minutes longer than XiO. None of the five gantry angles
      differed significantly between the two programs, but four of the five couch
      angles did. Dose-volume histogram (DVH) data showed a significantly better
      conformality index, and trends toward decreased hot spots and increased coverage
      of the planed treatment volume (PTV) when using VRS. However, when angels were
      chosen in VRS a greater volume of the ipsilateral breast received a low dose of
      radiation (between 3% and 50% of the prescribed dose) (VRS = 23.06%, XiO =
      19.57%, p < 0.0005). A significant advantage that VRS provided over XiO was the
      ability to detect potential collisions prior to actual treatment of the patient
      in three of the ten patients studied. The potential to save time with VRS by not
      having to redo plans because of a collision increases clinic efficiency.

PMID- 22417059
TI  - B-Spline registration based on new concept of an intelligent masking procedure
      and GPU computations for the head and neck adaptive tomotherapy.
AB  - The deformable image registration (DIR) procedure has been optimized for helical
      tomotherapy. The data on registration shifts obtained on matching planning image
      with pre-treatment megavoltage CT are used in our software for acceleration of
      the first step (rigid registration) of the DIR procedure and for implementation
      of the B-Spline algorithm with intelligent masking. Priorities of the masks were
      automatically calculated based on disagreement detected during rigid
      registration. Evaluation tasks included: (a) comparison of accuracy and rate for
      schemes of pre-registered and non-registered images; (b) qualification of the
      effectiveness of the intelligent masking process, and (c) determination of
      acceleration of achievable with GPU computing. A specially designed head and neck
      phantom used for evaluation included structures with controlled changes of
      position, volume, density, and shape. Re-contouring procedures were performed
      with an Adaptive Planning software (Tomotherapy Inc.). No statistical difference
      was observed in accuracy of DIR based on structure position match on the
      tomotherapy unit and non pre-registered images (p > 0.7). Using pre-registered
      data reduces the total time required for execution of the elastic registration
      procedure by 5%. These data are also necessary for intelligent masking procedure
      during B-Spine registration. Intelligent masking procedure increases accuracy of
      the registration for a masked structure (p < 0.04) without decreasing the
      accuracy in non-masked tissues and additionally reduces the total time by 13%.
      GPU computations speed up procedure 30 times. GPU computing of the DIR in current
      status of our investigation could be realized in a relatively short time after
      pre-treatment imaging. The proposed approach can be used in the routine
      assessment of anatomic changes occurring in healthy tissue during the course of
      radiotherapy. Further developments will be concentrated on the full integration
      of DIR computations in the imaging and treatment process of helical tomotherapy.

PMID- 22417060
TI  - In vivo photoacoustic tomography of total blood flow and potential imaging of
      cancer angiogenesis and hypermetabolism.
AB  - Blood flow is a key parameter in studying cancer angiogenesis and
      hypermetabolism. Current photoacoustic blood flow estimation methods focus on
      either the axial or transverse component of the flow vector. However, the Doppler
      angle (beam-to-flow angle) is needed to calculate the total flow speed, and it
      cannot always be estimated accurately in practice, especially when the system's
      axial and lateral resolutions are different. To overcome this problem, we propose
      a method to compute the total flow speed and Doppler angle by combining the axial
      and transverse flow measurements. The method has been verified by flowing bovine
      blood in a plastic tube at various speeds and Doppler angles. The error was
      experimentally determined to be less than 0.3 mm/s for total flow speed, and less
      than 158 for the Doppler angle. In addition, the method was tested in vivo on a
      mouse ear. We believe that the proposed method has the potential to be used for
      cancer angiogenesis and hypermetabolism imaging.

PMID- 22417061
TI  - High fat mixed lipid diet modifies protective effects of exercise on 1,2
      dimethylhydrazine induced colon cancer in rats.
AB  - The aim of the present study was to evaluate the effect of long-term swimming
      exercise in conjunction with a high fat mixed lipid (HFML) diet on colon cancer
      (CC) development and lipid peroxidation in the large bowel. We used forty male
      Wistar rats, which were randomly divided into one control group and four cancer
      groups: sedentary and swimming groups fed a standard diet (LFCO) and sedentary
      and swimming groups fed an HFML diet. Corticosterone was determined during the
      experiment. After 6 months of swimming, the rats were sacrificed and blood,
      heart, liver, muscle and large bowel were taken for determining the activity of
      serum enzymes, antioxidant capacity and CC development. The results demonstrate
      that exercise has a protective role in CC development. Attenuated development of
      CC and increased levels of malondialdehyde (MDA) in the large bowel of exercised
      rats show that one of the protective effects of exercise on developing CC is
      induction of oxidative stress. However, in terms of the combined effects of
      dietary fat and exercise, our results indicate that the protective role of
      exercise on CC development is significantly depressed by an HFML diet. An HFML
      diet significantly reduced the protective influence of exercise on colon
      carcinogenesis in rats and affected the degree of peroxidation in the large bowel
      during exercise, as well as concentrations of serum enzymes (LDH, alpha-HBDH, CK,
      ALT and AST). Our results indicate that an HFML diet, which reflects the
      composition of a Western style diet, is a significant modifier of the protective
      effects of exercise on CC development in rats.

PMID- 22417062
TI  - Proton radiotherapy for solid tumors of childhood.
AB  - The increasing efficacy of pediatric cancer therapy over the past four decades
      has produced many long-term survivors that now struggle with serious treatment
      related morbidities affecting their quality of life. Radiation therapy is
      responsible for a significant proportion of these late effects, but a relatively
      new and emerging modality, proton radiotherapy hold great promise to drastically
      reduce these treatment related late effects in long term survivors by sparing
      dose to normal tissues. Dosimetric studies of proton radiotherapy compared with
      best available photon based treatment show significant dose sparing to developing
      normal tissues. Furthermore, clinical data are now emerging that begin to
      quantify the benefit in decreased late treatment effects while maintaining
      excellent cancer control rates.

PMID- 22417063
TI  - Comparative proteome analysis of human lung squamous carcinoma using two
      different methods: two-dimensional gel electrophoresis and iTRAQ analysis.
AB  - Discovery of early-diagnosis biomarkers is the key to improve the early-diagnosis
      and prognosis of human lung squamous carcinoma (hLSC). In order to identify more
      exhaustive and systematic protein biomarkers for early-diagnosis of hLSC, we
      chose LCM purifed cells from hLSC tissues and paired normal bronchial
      epithelia(NBE) tissues and used two methods, the classical 2-DE/MS approach and
      the new iTRAQ analysis. We found a total of 63 differential proteins, 22 proteins
      in 2-DE and 59 proteins in iTRAQ analysis, between hLSC and NBE tissues. Among
      them, 18 proteins were quantified using both methods. The expression level of 15
      proteins (68.2%) in 2-DE was consistent with that in iTRAQ analysis. Series of
      proteins involved in cytoskeleton, chaperone, GTP binding, metabolic process,
      cell apoptosis, cell proliferation and differentiation, signal transduction,
      transcription and translation were identified, suggesting their possible role in
      the emergence of oncogenic pathways leading to carcinogenesis of hLSC. These
      proteins may make as potential biomarkers for diagnosis of hLSC. The two methods
      gave us closely related but different information about proteins, suggesting they
      are complementary or at least supplementary methods at present. Our results show
      both the usefulness of iTRAQ reagent technology for identification of further
      potential marker proteins as well as for prevalidation of biomarker.

PMID- 22417064
TI  - Reproducibility and comparison of DCE-MRI and DCE-CT perfusion parameters in a
      rat tumor model.
AB  - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and computed
      tomography (DCE-CT) provide independent measures of biomarkers related to tumor
      perfusion. We compared the reproducibilities and absolute values of DCE-MRI and
      DCE-CT biomarkers in the same tumors in an animal model, to investigate the
      physiologic validity of both approaches. DCE-MRI and DCE-CT were each performed
      sequentially on three consecutive days in each of twelve rats bearing C6 glioma
      xenografts. DCE-MRI yielded endothelial transfer constant (K(trans)),
      extracellular, extravascular space volume fraction (v(e)), and contrast agent
      reflux rate constant (k(ep)); and DCE-CT, blood flow (BF), blood volume (BV),
      mean transit time (MTT), and permeability-surface area product (PS) using Tofts
      and deconvolution physiological models, with 6.6 and 0.4 seconds temporal
      resolutions, respectively. Variability in DCE-CT and DCE-MRI were evaluated by
      variance components analysis. Intra-rat coefficients of variation for DCE-CT
      parameters BF, BV, MTT and PS were 25%, 22%, 18% and 23%; and for DCE-MRI
      parameters K(trans), k(ep) and v(e) were 23%, 16% and 20%, respectively. Mean (+/
      SD) BF, BV, MTT and PS were: 44.6 (+/-13.7) ml min(-1) 100 g(-1), 5.7 (+/-1.5) ml
      100 g(-1), 10.8 (+/-2.3) seconds, and 14.6 (+/-4.7) ml min(-1) 100 g(-1),
      respectively. Mean (+/-SD) K(trans), k(ep) and v(e) were: 0.21 (+/-0.05) min(-1),
      0.68 (+/-0.14) min(-1), and 0.29 (+/-0.06), respectively. Permeability estimates
      from DCE-MRI (K(trans)) were 44% higher than from DCE-CT (PS), despite
      application of appropriate corrections. DCE-MRI and DCE-CT biomarkers of tumor
      perfusion have similar reproducibilities suggesting that they may have comparable
      utility, but their derived parameter values are not equivalent.

PMID- 22417065
TI  - Therapist mindfulness, alliance and treatment outcome.
AB  - The present study investigated the association between therapist dispositional
      mindfulness and therapist self-affiliation, the therapeutic alliance, and
      treatment outcome. Total therapist mindfulness was associated with therapist self
      affiliation, r=.413, p<.05. Therapist mindfulness was positively correlated with
      therapist ratings of the working alliance, r=.456, p<.05, though only the Act
      with Awareness subscale showed a relationship with patient rated alliance,
      r=.379. Therapist mindfulness was not associated with patient rated decreases in
      global symptomatology, but was associated with patient rated improvements in
      interpersonal functioning, r=.481, p<.05. All correlations correspond to a medium
      effect size. The results indicate that therapist dispositional mindfulness may be
      an important pre-treatment variable in psychotherapy outcome.

PMID- 22417066
TI  - Resveratrol enhances radiation sensitivity in prostate cancer by inhibiting cell
      proliferation and promoting cell senescence and apoptosis.
AB  - Radiation therapy (XRT) for treatment of localized prostate cancer (PCA) has
      outcomes similar to surgery and medical therapy. Toxicities of XRT and the
      relative radioresistance of PCA limit the effectiveness of this treatment method.
      Safe and effective radiosensitizing agents are lacking to enhance the
      effectiveness for XRT for PCA. In this study, the effect of XRT in combination
      with the radiosensitizing agent resveratrol (RSV) was investigated in a
      radioresistant PCA cell line, PC-3. Our results show the addition of RSV to XRT
      (XRT/RSV) synergistically enhanced XRT-induced apoptosis and inhibition of PC-3
      proliferation. The antiproliferative effect of XRT/RSV treatment correlated with
      increased expression of p15, p21, and mutant p53 and decreased expression of
      cyclin B, cyclin D, and cdk2. Increased apoptosis correlated with increased
      expression of Fas and TRAILR1. Furthermore, XRT/RSV had little effect on the
      expression of p-AKT, whereas it increased the expression level of p-H2A.X, a
      marker for senescence. These data highlight the potential of RSV as a radiation
      sensitizer for PCA treatment and warrant further investigation.

PMID- 22417067
TI  - Representations in dynamical embodied agents: re-analyzing a minimally cognitive
      model agent.
AB  - Understanding the role of ''representations'' in cognitive science is a
      fundamental problem facing the emerging framework of embodied, situated,
      dynamical cognition. To make progress, I follow the approach proposed by an
      influential representational skeptic, Randall Beer: building artificial agents
      capable of minimally cognitive behaviors and assessing whether their internal
      states can be considered to involve representations. Hence, I operationalize the
      concept of representing as ''standing in,'' and I look for representations in
      embodied agents involved in simple categorization tasks. In a first experiment,
      no representation can be found, but the relevance of the task is undermined by
      the fact that agents with no internal states can reach high performance. A simple
      modification makes the task more "representationally hungry," and in this case,
      agents' internal states are found to qualify as representations. I conclude by
      discussing the benefits of reconciling the embodied-dynamical approach with the
      notion of representation.

PMID- 22417069
TI  - Abstracts of the 5th Biennial Conference of the International Society for Bipolar
      Disorders. March 14-17, 2012. Istanbul, Turkey.

PMID- 22417070
TI  - Response-related negativities following correct and incorrect responses: evidence
      from a temporospatial principal component analysis.
AB  - Two ERP components have been observed following correct and incorrect responses,
      the error-related negativity (ERN/Ne) and the correct-related negativity (CRN).
      The function of these components is still under debate. We used a visual size
      discrimination task at three difficulty levels and utilized a temporospatial
      principal component analysis (PCA) to examine whether ERN/Ne and CRN could be
      explained by one or more factors. While ERN/Ne decreased with higher task
      difficulty, amplitudes increased for correct responses at parietal electrodes.
      PCA revealed two temporospatial factors: a centrally distributed factor differing
      between correct and incorrect responses and a more frontoparietally distributed
      factor contributing to both ERN/Ne and CRN. These data support the notion that
      ERN/Ne and CRN might reflect a combination of two underlying processes: an error
      sensitive and an outcome-independent aspect of response monitoring.

PMID- 22417068
TI  - Pandemic (H1N1) 2009 influenza in Canadian pediatric cancer and hematopoietic
      stem cell transplant patients.
AB  - BACKGROUND: The impact of pandemic H1N1 influenza (pH1N1) virus in pediatric
      cancer is uncertain. The objectives of this study were to characterize the
      clinical course of pH1N1 and identify factors associated with severe outcomes.
      METHODS: We conducted a Canadian multicenter retrospective review of children
      with cancer and stem cell transplant (SCT) recipients who were diagnosed with
      laboratory-confirmed pH1N1 infection between May 1, 2009 and January 31, 2010.
      RESULTS: We identified 100 (19 in wave 1 and 81 in wave 2) cases of pH1N1
      infection. Median age was 8.7 years. 71% had a hematologic malignancy, and 20%
      received SCT. Median duration of fever and illness was 2 and 12.5 days,
      respectively. 51 (51.5%) were hospitalized for a median of 5 days, with no deaths
      and only 1 requiring admission to the intensive care unit. Radiologically
      confirmed pneumonia was diagnosed in 10 (10%). Interruption of chemotherapy or
      conditioning occurred in 43 patients. In multivariable analyses, age <5 years
      (relative to >= 10 years) and neutropenia were associated with hospitalization
      while neutropenia was associated with pneumonia. Despite oseltamivir use in 89%,
      viral shedding was prolonged (median, 46 days) and often persisted after symptom
      resolution. However, an extended treatment course (>5 days) correlated with
      shortened duration of viral shedding (P=0.041). CONCLUSIONS: pH1N1 infection in
      pediatric cancer and SCT patients infrequently caused complications but commonly
      interrupted cancer treatment. Persistent shedding of virus after illness
      resolution was common. Further research is needed to verify this finding as it
      could have implications for treatment guidelines and infection control practices.

PMID- 22417071
TI  - Long-term seizure outcome and risk factors for recurrence after extratemporal
      epilepsy surgery.
AB  - PURPOSE: We aimed to assess long-term seizure outcome and risk factors for
      seizure recurrence in a cohort of patients who have undergone extratemporal
      resection for management of refractory seizures. METHODS: Eighty-one patients
      underwent extratemporal resection at Austin Health, Melbourne, Australia (1991
      2004). Seizure recurrence was any postoperative disabling seizure (complex
      partial seizure [CPS] +/- secondary generalization). Multivariate Cox
      proportional hazards regression models examined potential preoperative and
      perioperative risk factors and the risk associated with early postoperative
      seizures (<= 28 days postsurgery). The change between preoperative and
      postoperative seizure frequency was also measured. KEY FINDINGS: Median follow-up
      was 10.3 years (range 1-17.7). The probabilities of freedom from disabling
      seizures (on or off antiepileptic medication) were 40.7% (95% confidence interval
      [CI] 30-51) at 1 month, 23.5% (95% CI 15-33) at 1 year, and 14.7% (95% CI 8-23)
      at 5 years postoperative. Reduction of disabling seizures to at least 20% of
      preoperative frequency was attained by 57% of patients at 5 postoperative years.
      Of the preoperative/perioperative factors, focal cortical dysplasia (FCD) type 1
      (hazard ratio [HR] 1.90, 95% CI 1.08-3.34, p = 0.025) and incomplete resection
      (HR 1.71, 95% CI 1.06-2.76, p = 0.028) were independent recurrence risks. After
      surgery, an early postoperative seizure was the only factor associated with
      higher risk (HR 4.28 [2.42-7.57], p = 0.00). SIGNIFICANCE: Distinction between
      subtypes of focal cortical dysplasia, which can be made using magnetic resonance
      imaging (MRI) criteria, may be useful for preoperative prognostication. Early
      seizures after surgery are not benign and may be markers of factors that
      contribute to seizure recurrence. Most patients achieve substantial reduction in
      seizure frequency. Further study of the significance of this reduction in terms
      of surgical "success" or otherwise is required.

PMID- 22417072
TI  - Safety of long-term nucleos(t)ide treatment in chronic hepatitis B.
AB  - Currently, five nucleos(t)ide analogs (NAs) are approved for the treatment of
      chronic hepatitis B (CHB) infection. They are lamivudine, adefovir dipivoxil,
      telbivudine, entecavir (ETV) and tenofovir disoproxil fumarate (TDF). Two of
      them, ETV and TDF, are recommended as first-line treatment options. Their main
      advantages include excellent tolerability, antiviral potency and a high genetic
      barrier to resistance within medium duration treatment periods (2 - 6 years). In
      most patients, NAs need to be administered on a long-term basis. Several studies
      suggest that NAs long-term administration have been associated with low rates of
      serious adverse events (AEs), including lactic acidosis, renal function
      impairment, osteopenia and osteoporosis. Discontinuations due to AEs tended to be
      low in published randomized clinical trial and in the experience in clinical
      practice. NAs long-term use appears to be safe and effective; and in patients
      with advanced liver disease, despite preliminary concerning reports, their short
      term use also appears to be safe and effective. Although major AEs are
      infrequent, they can be initially clinically silent yet lead to serious medical
      problems, therefore, a proactive surveillance and their prompt management is
      recommended.

PMID- 22417073
TI  - Phylogenetics and evolution of Trx SET genes in fully sequenced land plants.
AB  - Plant Trx SET proteins are involved in H3K4 methylation and play a key role in
      plant floral development. Genes encoding Trx SET proteins constitute a multigene
      family in which the copy number varies among plant species and functional
      divergence appears to have occurred repeatedly. To investigate the evolutionary
      history of the Trx SET gene family, we made a comprehensive evolutionary analysis
      on this gene family from 13 major representatives of green plants. A novel
      clustering (here named as cpTrx clade), which included the III-1, III-2, and III
      4 orthologous groups, previously resolved was identified. Our analysis showed
      that plant Trx proteins possessed a variety of domain organizations and gene
      structures among paralogs. Additional domains such as PHD, PWWP, and FYR were
      early integrated into primordial SET-PostSET domain organization of cpTrx clade.
      We suggested that the PostSET domain was lost in some members of III-4
      orthologous group during the evolution of land plants. At least four classes of
      gene structures had been formed at the early evolutionary stage of land plants.
      Three intronless orphan Trx SET genes from the  Physcomitrella patens  (moss)
      were identified, and supposedly, their parental genes have been eliminated from
      the genome. The structural differences among evolutionary groups of plant Trx SET
      genes with different functions were described, contributing to the design of
      further experimental studies.

PMID- 22417074
TI  - Comparison of effects of clodronate and zoledronic acid on the repair of maxilla
      surgical wounds - histomorphometric, receptor activator of nuclear factor-kB
      ligand, osteoprotegerin, von Willebrand factor, and caspase-3 evaluation.
AB  - BACKGROUND: The aim of this study was to compare clodronate and zoledronic acid
      regarding their influence on the repair of surgical wounds in maxillae (soft
      tissue wound and tooth extraction) and their relation to osteonecrosis. MATERIAL
      AND METHODS: Thirty-four Wistar rats were allocated into three groups according
      to the treatment received: (i) 12 animals treated with zoledronic acid, (ii) 12
      animals treated with clodronate and (iii) 10 animals that were given saline
      solution. All animals were subjected to tooth extractions and surgically induced
      soft tissue injury. Histological analysis of the wound sites was performed by
      means of hematoxylin-eosin (H&E) staining and immunohistochemical staining for
      receptor activator of nuclear factor-kB ligand (RANKL), osteoprotegerin (OPG),
      von Willebrand factor, and caspase-3. RESULTS: The zoledronic acid group showed
      higher incidence of non-vital bone than did the clodronate group at the tooth
      extraction site. At the soft tissue wound site, there were no significant
      differences in non-vital bone between the test groups. RANKL, OPG, von Willebrand
      factor, and caspase-3 did not show significant differences between the groups for
      both sites of surgical procedures. CONCLUSION: Both of the bisphosphonates
      zoledronic acid and clodronate are capable of inducing maxillary osteonecrosis.
      Immunohistochemical analysis suggests that the involvement of soft tissues as the
      initiator of osteonecrosis development is less probable than has been pointed
      out.

PMID- 22417075
TI  - Expression of genes involved in hepatic carnitine synthesis and uptake in dairy
      cows in the transition period and at different stages of lactation.
AB  - BACKGROUND: In rodents and pigs, it has shown that carnitine synthesis and uptake
      of carnitine into cells are regulated by peroxisome proliferator-activated
      receptor alpha (PPARA), a transcription factor which is physiologically activated
      during fasting or energy deprivation. Dairy cows are typically in a negative
      energy balance during early lactation. We investigated the hypothesis that genes
      of carnitine synthesis and uptake in dairy cows are enhanced during early
      lactation. RESULTS: mRNA abundances of PPARA and some of its classical target
      genes and genes involved in carnitine biosynthesis [trimethyllysine dioxygenase
      (TMLHE), 4-N-trimethylaminobutyraldehyde dehydrogenase (ALDH9A1), gamma
      butyrobetaine dioxygenase (BBOX1)] and uptake of carnitine [novel organic cation
      transporter 2 (SLC22A5)] as well as carnitine concentrations in liver biopsy
      samples of 20 dairy cows in late pregnancy (3 wk prepartum) and early lactation
      (1 wk, 5 wk, 14 wk postpartum) were determined. From 3 wk prepartum to 1 wk
      postpartum, mRNA abundances of PPARAlpha and several PPARAlpha target genes
      involved in fatty acid uptake, fatty acid oxidation and ketogenesis in the liver
      were strongly increased. Simultaneously, mRNA abundances of enzymes of carnitine
      synthesis (TMLHE: 10-fold; ALDH9A1: 6-fold; BBOX1: 1.8-fold) and carnitine uptake
      (SLC22A5: 13-fold) and the concentration of carnitine in the liver were increased
      from 3 wk prepartum to 1 wk postpartum (P < 0.05). From 1 wk to 5 and 14 wk
      postpartum, mRNA abundances of these genes and hepatic carnitine concentrations
      were declining (P < 0.05). There were moreover positive correlations between
      plasma concentrations of non-esterified fatty acids (NEFA) and hepatic carnitine
      concentrations at 1 wk, 5 wk and 14 wk postpartum (P < 0.05). CONCLUSIONS: The
      results of this study show for the first time that the expression of hepatic
      genes of carnitine synthesis and cellular uptake of carnitine is enhanced in
      dairy cows during early lactation. These changes might provide an explanation for
      increased hepatic carnitine concentrations observed in 1 wk postpartum and might
      be regarded as a physiologic means to provide liver cells with sufficient
      carnitine required for transport of excessive amounts of NEFA during a negative
      energy balance.

PMID- 22417076
TI  - Dramatic decrease of carnitine esters after interruption of exogenous carnitine
      supply in hemodialysis patients.
AB  - L-carnitine supplementation is extensively used in patients on maintenance
      hemodialysis (HD) to improve dialysis-related clinical symptoms. In a series of
      studies, we investigated the dynamics of carnitine pool in carnitine-supplemented
      HD patients; here we report dramatic decrease with special changes of the ester
      profile due to interruption of the exogenous intake after the last HD session.
      Serum samples were collected from 18 L-carnitine-repleted end-stage renal disease
      (ESRD) patients before the L-carnitine supplementation, after completion of a
      carnitine supplementation period treatment (12 weeks, 1 g/IV/HD), right before
      the HD session, and 44 h after the dialysis. Levels of free carnitine (FC) and
      the individual esters were determined using electrospray MS/MS technique.
      Normally, L-carnitine supplementation causes significant elevation of all
      carnitine compounds to supraphysiological levels, which reaches a standard steady
      state-like profile. In this study we found a dramatic decrease in the level of
      FC, and in short- and medium-chain acylcarnitines (ACs) 44 h after the last
      dialysis. At the end of this interdialytic period, FC levels increased to only
      65% of the predialysis level, whereas the amounts of C2 and C3 esters recovered
      to only 50%. The level of C6 was 65% of the predialysis level, whereas the amount
      of C8 chain length ACs returned to 72% of the predialysis level. No significant
      change was seen in AC concentrations above C10 chain length. Omission of one
      single dosage of supplemental carnitine in long-term administration schemes
      results in dramatic decrease and reprofiling of carnitine esters even after the
      usual 44 h of interdialytic period.

PMID- 22417077
TI  - Simultaneous perineal ultrasound and vaginal pressure measurement prove the
      action of electrical pudendal nerve stimulation in treating female stress
      incontinence.
AB  - Study Type - Diagnostic (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? Pelvic floor muscle training (PFMT) and
      transvaginal electrical stimulation (TES) are two commonly used forms of
      conservative treatment for stress urinary incontinence (SUI). PFMT may build up
      the structural support of the pelvis, but many SUI patients are unable to perform
      PFMT effectively and its primary disadvantage is lack of long-term patient
      compliance. TES is a passive treatment that produces PFM contraction and patient
      compliance with it is good; however, its effect is not as good as that of PFMT
      when performed correctly. Electrical pudendal nerve stimulation (EPNS) combines
      the advantages of PFMT and TES and incorporates the technique of deep insertion
      of long needles. In this study, simultaneous perineal ultrasound and vaginal
      pressure measurement prove that EPNS can contract the PFM and simulate PFMT. It
      is shown that EPNS is an alternative therapy for female SUI patients who fail
      PFMT and TES and the therapy can also be used for severe SUI. OBJECTIVES: * To
      prove that electrical pudendal nerve stimulation (EPNS) can contract the pelvic
      floor muscles (PFM) and simulate pelvic floor muscle training (PFMT). * To show
      that EPNS is an alternative therapy for female stress urinary incontinence (SUI)
      that does not respond effectively to PFMT and transvaginal electrical stimulation
      (TES). PATIENTS AND METHODS: * Thirty-five female patients with SUI who did not
      respond effectively to PFMT and TES (group I) were enrolled and 60 other female
      patients with SUI were allocated to group II (30 patients) and group III (30
      patients). * Long needles were deeply inserted into four sacral points and
      electrified to stimulate the pudendal nerves. Group I and group II were treated
      by a doctor skilled in performing EPNS and group III, by a doctor unskilled in
      performing EPNS. * When EPNS was performed in group I, perineal ultrasonographic
      PFM movements, vaginal pressure (VP) and PFM electromyography were recorded
      simultaneously. * The therapeutic effects were evaluated according to objective
      and subjective criteria RESULTS: * When EPNS was performed correctly, the patient
      felt strong PFM contractions. Simultaneous recordings in group I showed: B-mode
      cranio-caudal PFM movements; M-mode PFM movement curves (amplitude: about 1 mm,
      n= 31); a sawtooth curve of VP changes (2.61 +/- 1.29 cmH(2) O, n= 34); and PFM
      myoelectric waves (amplitude: 23.9 +/- 25.3 uV). * If during the EPNS process the
      electric current was stopped or its intensity was reduced to about 7-12 mA or the
      two lower needles were drawn back, then the above ultrasonographic PFM movements
      and VP changes disappeared. * In group I, the incontinence severity and quality
      of life score was 16.5 +/- 4.0 before treatment and decreased to 4.2 +/- 4.0
      after 27.5 +/- 11.9 sessions of treatment (P < 0.01). At the end of treatment,
      100% improvement occurred in 16 cases (45.7%). A 2-year follow-up showed that
      100% improvement occurred in 14 of cases (40.0%). * In group II, the incontinence
      severity and quality of life score was 17.1 +/- 6.3 before treatment and
      decreased to 3.5 +/- 3.7 after 10 sessions of treatment (P < 0.01) and 100%
      improvement occurred in 12 cases (40.0%). In group III, the incontinence severity
      and quality of life score was 17.6 +/- 6.3 before treatment and decreased to 10.8
      +/- 8.2 after 10 sessions of treatment (P < 0.01) and 100% improvement occurred
      in one case (3.3%). * The post-treatment score was lower and the therapeutic
      effect was better in group II than in group III (both P < 0.01). CONCLUSIONS: *
      EPNS can contract the PFM and simulate PFMT. * EPNS is an alternative therapy for
      female SUI patients who fail PFMT and TES.

PMID- 22417078
TI  - Enantioselective Bronsted base catalysis with chiral cyclopropenimines.
AB  - Cyclopropenimines are shown to be a highly effective new class of
      enantioselective Bronsted base catalysts. A chiral 2,3
      bis(dialkylamino)cyclopropenimine catalyzes the rapid Michael reaction of a
      glycine imine substrate with high levels of enantioselectivity. A preparative
      scale reaction to deliver 25 g of product is demonstrated, and a trivial large
      scale synthesis of the optimal catalyst is shown. In addition, the basicity of a
      2,3-bis(dialkylamino)cyclopropenimine is measured for the first time and shown to
      be approximately equivalent to the P(1)-tBu phosphazene base. An X-ray crystal
      structure of the protonated catalyst is shown along with a proposed mechanistic
      and stereochemical rationale.

PMID- 22417079
TI  - Primary Burkitt's lymphoma of the colon--an uncommon cause of acute constipation
      and abdominal pain.
AB  - Constipation is a common problem in children and adolescents, accounting for over
      25% of all visits to pediatric gastroenterologists. Approximately 95% of
      childhood constipation is functional in nature. Primary gastrointestinal
      malignancies are rare in childhood and adolescence. When present in the
      gastrointestinal tract, Burkitt's lymphoma is typically located in the ileocecal
      region. We present a case of primary Burkitt's lymphoma of the transverse colon
      in an adolescent presenting with acute exacerbation of constipation, abdominal
      pain, and later, rectal bleeding and progressive weight loss.

PMID- 22417080
TI  - Comparative cytotoxicity induced by bulk and nanoparticulated ZnO in the fish and
      human hepatoma cell lines PLHC-1 and Hep G2.
AB  - The increasing presence of ZnO nanoparticles (NPs) in consumer products may be
      having a dramatic impact in aquatic environments. The evaluation of ZnO NP
      toxicity represents a great challenge. This study aimed at evaluating the
      cytotoxic effect of micro- and nanosized ZnO in a fish and a mammalian hepatoma
      cell line. A detailed characterisation of the particles in exposure media showed
      that ZnO NPs formed large aggregates. ZnO cytotoxicity was evaluated with a
      battery of in vitro assays including LUCS, a new approach based on DNA alteration
      measurements. In fish cells, ZnO NP aggregates contributed substantially to the
      cytotoxic effects whereas toxicity in the human cells appeared to be mainly
      produced by the dissolved fraction. ROS production did not contribute to the
      observed cytotoxicity. This work also showed that measuring concentrations of NPs
      is essential to understand the mechanisms underlying their toxicity.

PMID- 22417081
TI  - Multiple basal cell carcinomas in an atomic bomb survivor.

PMID- 22417082
TI  - Understanding age-specific dispersal in fishes through hydrodynamic modelling,
      genetic simulations and microsatellite DNA analysis.
AB  - Many marine species have vastly different capacities for dispersal during larval,
      juvenile and adult life stages, and this has the potential to complicate the
      identification of population boundaries and the implementation of effective
      management strategies such as marine protected areas. Genetic studies of
      population structure and dispersal rarely disentangle these differences and
      usually provide only lifetime-averaged information that can be considered by
      managers. We address this limitation by combining age-specific autocorrelation
      analysis of microsatellite genotypes, hydrodynamic modelling and genetic
      simulations to reveal changes in the extent of dispersal during the lifetime of a
      marine fish. We focus on an exploited coral reef species, Lethrinus nebulosus,
      which has a circum-tropical distribution and is a key component of a multispecies
      fishery in northwestern Australia. Conventional population genetic analyses
      revealed extensive gene flow in this species over vast distances (up to 1,500
      km). Yet, when realistic adult dispersal behaviours were modelled, they could not
      account for these observations, implying adult dispersal does not dominate gene
      flow. Instead, hydrodynamic modelling showed that larval L. nebulosus are likely
      to be transported hundreds of kilometres, easily accounting for the observed gene
      flow. Despite the vast scale of larval transport, juvenile L. nebulosus exhibited
      fine-scale genetic autocorrelation, which declined with age. This implies both
      larval cohesion and extremely limited juvenile dispersal prior to maturity. The
      multidisciplinary approach adopted in this study provides a uniquely
      comprehensive insight into spatial processes in this marine fish.

PMID- 22417083
TI  - The power of subtle interpersonal hostility in psychodynamic psychotherapy: a
      speech acts analysis.
AB  - This study compared participants' speech acts in low-hostile versus moderate
      hostile interpersonal episodes in time-limited psychodynamic psychotherapy. Sixty
      two cases from the Vanderbilt II psychotherapy project were categorized as low or
      moderate in interpersonal hostility based on ratings of interpersonal process
      using Structural Analysis of Social Behavior (Benjamin, 1996). Representative
      episodes were coded using a taxonomy of speech acts (Stiles, 1992), and speech
      acts were compared across low- and moderate-hostile episodes. Therapists in
      moderate-hostility episodes used more interpretations and edifications, and fewer
      questions and reflections. Patients in moderate-hostility episodes used more
      disclosures and fewer edifications. Content coding showed that therapist
      interpretations with a self/intrapsychic self focus were more characteristic of
      moderate-hostility than low-hostility episodes, whereas the two types of episodes
      contained similar levels of interpretations focused on the patient's
      interpersonal relationships and the therapeutic relationship.

PMID- 22417084
TI  - Editorial.

PMID- 22417085
TI  - Decreased GH dose after the catch-up growth period maintains metabolic outcome in
      short prepubertal children with and without classic GH deficiency.
AB  - OBJECTIVE: Few studies have evaluated metabolic outcomes following growth hormone
      (GH) treatment in short prepubertal children during different periods of growth.
      Previously, we found that individualized GH dosing in the catch-up period reduced
      the variation in fasting insulin levels by 34% compared with those receiving a
      standard GH dose. We hypothesized that the GH dose required to maintain
      beneficial metabolic effects is lower during the prepubertal growth phase after
      an earlier catch-up growth period. DESIGN: Short prepubertal children with
      isolated GH deficiency or idiopathic short stature were randomized to
      individualized GH treatment (range, 17-100 MUg/kg/day) or a standard dose in a
      preceding 2-year study. After achieving near mid-parental height(SDS) , children
      receiving an individualized dose were randomized to either a 50% reduced
      individualized dose (RID, n = 28) or an unchanged individualized dose (UID, n =
      37) for 2 years. The dose remained unchanged in 33 children initially randomized
      to receive a standard dose (FIX, 43 MUg/kg/day).We evaluated whether the
      variations in metabolic parameters measured during maintenance growth diminished
      in RID compared with UID or FIX. RESULTS: We observed less variation in fasting
      insulin levels (-50%), insulin sensitivity as assessed by homoeostasis model
      assessment (-55.1%), lean soft tissue (-27.8%) and bone mineral content (-31.3%)
      in RID compared with UID (all P < 0.05), but no differences compared with FIX.
      CONCLUSIONS: Continued reduced individualized GH treatment after the catch-up
      growth period is safe and reduces hyperinsulinism. Individualized GH dose can be
      reduced once the desired height(SDS)  is achieved to avoid overtreatment in terms
      of metabolic outcome.

PMID- 22417086
TI  - Expression of TREM-1 in hepatic stellate cells and prognostic value in hepatitis
      B-related hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a typical inflammation-related malignancy
      characterized by high postoperative recurrence and metastasis. Although several
      inflammatory cells and inflammatory signatures have been linked to poor
      prognosis, the inflammation-associated molecular mechanisms of HCC development
      and progression are largely unknown. Here we show that triggering receptor
      expressed in myeloid cells (TREM)-1, a transmembrane receptor expressing in
      myeloid cells, was also expressed in tumor-activated hepatic stellate cells
      (HSCs) and associated with the aggressive behavior of HCC cells. Enzyme-linked
      immunosorbent assay was used to measure the expression levels of soluble TREM-1
      (sTREM-1) in activated hepatic stellate cells supernatant and 92 preoperative and
      postoperative plasmas of patients with malignancy and/or benign liver
      tumor/disease, respectively. Expression levels of TREM-1 were assessed by
      immunohistochemistry in tissue microarray from 240 patients with HCC. As a
      result, increased secretion of sTREM-1 from activated HSCs was observed after co
      culture with HCC cell lines (P < 0.001), and conditioned medium collected from
      activated HSCs/cancer associated myofibroblasts (CAMFs) with or without
      agonist/inhibitor of TREM-1 significantly changed the migratory ability of HCC
      cells. The levels of sTREM-1 were significantly higher in patients with HCC than
      those with benign liver tumors (P < 0.005). Peritumoral density of TREM-1 was
      shown to be an independent prognosis predictor according to univariate (P < 0.001
      for both overall survival and time to recurrence) and multivariate analysis (P =
      0.008 for overall survival; P = 0.005 for time to recurrence). Thus, these
      observations suggest that TREM-1 is related to the aggressive tumor behavior and
      has potential value as a prognostic factor for HCC.

PMID- 22417087
TI  - Loading mechanisms of ring helicases at replication origins.
AB  - Threading of DNA through the central channel of a replicative ring helicase is
      known as helicase loading, and is a pivotal event during replication initiation
      at replication origins. Once loaded, the helicase recruits the primase through a
      direct protein-protein interaction to complete the initial 'priming step' of DNA
      replication. Subsequent assembly of the polymerases and processivity factors
      completes the structure of the replisome. Two replisomes are assembled, one on
      each strand, and move in opposite directions to replicate the parental DNA during
      the 'elongation step' of DNA replication. Replicative helicases are the motor
      engines of replisomes powered by the conversion of chemical energy to mechanical
      energy through ATP binding and hydrolysis. Bidirectional loading of two ring
      helicases at a replication origin is achieved by strictly regulated and
      intricately choreographed mechanisms, often through the action of replication
      initiation and helicase-loader proteins. Current structural and biochemical data
      reveal a wide range of different helicase-loading mechanisms. Here we review
      advances in this area and discuss their implications.

PMID- 22417088
TI  - Ribonuclease S dynamics measured using a nitrile label with 2D IR vibrational
      echo spectroscopy.
AB  - A nitrile-labeled amino acid, p-cyanophenylalanine, is introduced near the active
      site of the semisynthetic enzyme ribonuclease S to serve as a probe of protein
      dynamics and fluctuations. Ribonuclease S is the limited proteolysis product of
      subtilisin acting on ribonuclease A, and consists of a small fragment including
      amino acids 1-20, the S-peptide, and a larger fragment including residues 21-124,
      the S-protein. A series of two-dimensional vibrational echo experiments performed
      on the nitrile-labeled S-peptide and the RNase S are described. The time
      dependent changes in the two-dimensional infrared vibrational echo line shapes
      are analyzed using the center line slope method to obtain the frequency-frequency
      correlation function (FFCF). The observations show that the nitrile probe in the
      S-peptide has dynamics that are similar to, but faster than, those of the single
      amino acid p-cyanophenylalanine in water. In contrast, the dynamics of the
      nitrile label when the peptide is bound to form ribonuclease S are dominated by
      homogeneous dephasing (motionally narrowed) contributions with only a small
      contribution from very fast inhomogeneous structural dynamics. The results
      provide insights into the nature of the structural dynamics of the ribonuclease S
      complex. The equilibrium dynamics of the nitrile labeled S-peptide and the
      ribonuclease S complex are also investigated by molecular dynamics simulations.
      The experimentally determined FFCFs are compared to the FFCFs obtained from the
      molecular dynamics simulations, thereby testing the capacity of simulations to
      determine the amplitudes and time scales of protein structural fluctuations on
      fast time scales under thermal equilibrium conditions.

PMID- 22417089
TI  - Grewialin and optivanin new constituents from the stem bark of Grewia optiva
      Drummond ex Burret (Tiliaceae).
AB  - Studies on the chemical constituents from the stem bark of Grewia optiva have led
      to the isolation of two new compounds, grewialin (1) and optivanin (2), along
      with three known constituents which were hitherto unreported from this species.
      The structures of the new constituents have been elucidated by spectral studies
      including 1D and 2D NMR experiments (HSQC, HMBC, COSY, NOESY and J-resolved) as
      well as HR EI-MS spectroscopic data analysis, as 2S*-(3-hydroxy-4-methoxyphenyl)
      3R*-methyl-2H-[1,4]-dioxin [2,3]-chromen-7(3H)-one (1); a coumarinolignan and 3
      hydroxy-1-(3-hydroxy-4-methoxyphenyl) propan-1-one (2). The known compounds were
      identified as beta-sitosterol, stigmasterol and lupeol by comparing their
      spectral data with those reported in the literature.

PMID- 22417090
TI  - Impaired hippocampal memory function and synaptic plasticity in experimental
      cortical dysplasia.
AB  - PURPOSE:   Memory impairment is a common comorbidity in people with epilepsy
      associated malformations of cortical development. We studied spatial memory
      performance and hippocampal synaptic plasticity in an animal model of cortical
      dysplasia. METHODS:   Embryonic day 17 rats were exposed to 2.25 Gy external
      radiation. One-month-old rats were tested for spatial recognition memory. After
      behavioral testing, short-term and long-term synaptic plasticity in the
      hippocampal CA1 region was studied in an in vitro slice preparation. KEY
      FINDINGS:   Behavioral assessments showed impaired hippocampal CA1-dependent
      spatial recognition memory in irradiated rats. Neurophysiologic assessments
      showed that baseline synaptic transmission was significantly enhanced, whereas
      paired-pulse facilitation, long-term potentiation, and long-term depression of
      the field excitatory postsynaptic potential (fEPSP) slope at Schaffer
      collateral/commissural fiber-CA1 synapses were significantly reduced in the
      irradiated rats. Histologic observations showed dysplastic cortex and dispersed
      hippocampal pyramidal neurons. SIGNIFICANCE:   This study has shown that
      prenatally irradiated rats with cortical dysplasia exhibit a severe impairment of
      spatial recognition memory accompanied by disrupted short-term and long-term
      synaptic plasticity and may help to guide development of potential therapeutic
      interventions for this important problem.

PMID- 22417091
TI  - Design and synthesis of novel lactate dehydrogenase A inhibitors by fragment
      based lead generation.
AB  - Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate,
      utilizing NADH as a cofactor. It has been identified as a potential therapeutic
      target in the area of cancer metabolism. In this manuscript we report our
      progress using fragment-based lead generation (FBLG), assisted by X-ray
      crystallography to develop small molecule LDHA inhibitors. Fragment hits were
      identified through NMR and SPR screening and optimized into lead compounds with
      nanomolar binding affinities via fragment linking. Also reported is their
      modification into cellular active compounds suitable for target validation work.

PMID- 22417092
TI  - Systematic reviews in small animal veterinary medicine: what are they and why do
      we need them?

PMID- 22417093
TI  - Syringosubarachnoid shunt as a management for syringohydromyelia in dogs.
AB  - OBJECTIVE: To evaluate retrospectively the efficacy of syringosubarachnoid shunt
      for the management of syringohydromyelia/syringomyelia. METHODS: Eleven dogs
      diagnosed with syringohydromyelia/syringomyelia by magnetic resonance imaging
      associated with Chiari-like malformation underwent placement of a
      syringosubarachnoid shunt at the cervical (nine dogs) or lumbar (two dogs) spinal
      cord. In one dog, a suboccipital decompression (foramen magnum decompression) was
      performed 4 months before inserting a syringosubarachnoid shunt. All dogs were
      evaluated neurologically a few hours after surgery, 2 weeks and 6 months
      postoperatively. Retrospectively, cases were assigned a preoperative and
      postoperative pain score. RESULTS: There were no intra- or peri-operative
      complications. One dog (9%) was euthanased 5 weeks after surgery. Progressive
      neurological improvement was observed in nine dogs (81.8%) 2 weeks and 6 months
      postoperatively. No clinical improvement was seen in another dog (9%). One dog
      (9%) had replacement of the syringosubarachnoid shunt. Seven dogs (63.6%) were
      still alive 1 to 4 years (mean, 2.6 years) after surgery. CLINICAL SIGNIFICANCE:
      Placement of a syringosubarachnoid shunt in the presence of a sufficiently large
      syrinx appears to be beneficial in dogs with Chiari-like malformation and
      associated syringohydromyelia/syringomyelia.

PMID- 22417094
TI  - Familial subvalvular aortic stenosis in golden retrievers: inheritance and
      echocardiographic findings.
AB  - OBJECTIVES: To describe the echocardiographic findings and pedigree analysis of
      golden retrievers with subvalvular aortic stenosis. METHODS: Seventy-three golden
      retrievers were evaluated by auscultation and echocardiography. A subcostal
      continuous-wave Doppler aortic velocity e2.5 m/s and presence of a left basilar
      systolic ejection murmur were required for diagnosis of subvalvular aortic
      stenosis. Three echocardiographic characteristics were recorded: evidence of
      aortic insufficiency, subvalvular ridge or left ventricular hypertrophy. A
      disease status score was calculated by totalling the number of echocardiographic 
      characteristics per subject. RESULTS: Thirty-two of 73 dogs were affected and
      their aortic velocities were as follows: range 2.5 to 6.8 m/s, median 3.4 m/s and
      standard deviation 1.2 m/s. Echocardiographic characteristics of 32 affected dogs
      were distributed as follows: left ventricular hypertrophy 12 of 32, aortic
      insufficiency 20 of 32 and subvalvular ridge 20 of 32. Disease status score
      ranged from 0 to 3 with a median of 2. There was a statistically significant
      correlation between aortic velocity and disease status score (r=0.644, P<0.0001).
      Subvalvular aortic stenosis was observed in multiple generations of several
      families and appears familial. CLINICAL SIGNIFICANCE: Subvalvular aortic stenosis
      in the golden retriever is familial. Severity of stenosis correlates well with
      cumulative presence of echocardiographic characteristics (left ventricular
      hypertrophy, subvalvular ridge and aortic insufficiency).

PMID- 22417095
TI  - Primary care veterinary usage of systemic glucocorticoids in cats and dogs in
      three UK practices.
AB  - OBJECTIVES: To describe systemic glucocorticoid usage in cats and dogs by three
      primary care -veterinary practices in England and to ascertain risk factors for
      clinical use. To evaluate consistency of prescribing patterns across clinics. To
      validate a merged database of primary veterinary clinical data as a functional
      tool for clinical epidemiological research. METHODS: A merged database was
      established from clinical data on 31,273 cat and dog consultations with
      pharmacotherapy from three veterinary practices in England. Descriptive
      statistics described systemic glucocorticoid drug use in cats and dogs while
      mixed-effects logistic regression modelling evaluated risk factors. Individual
      clinic usage was compared. RESULTS: Overall, 1877 (16.68%) cat consultations and
      2913 (14.55%) dog consultations resulted in systemic glucocorticoid therapy. Cats
      received higher parenteral (P<0.0001) and oral (P<0.0001) dose levels than dogs.
      Pathophysiological indication, age, skin condition, sex and clinic attended were
      significant risk factors for glucocorticoid prescription. Clinics varied widely
      in their odds of systemic glucocorticoid usage (P<0.0001). CLINICAL SIGNIFICANCE:
      An evidence base for systemic glucocorticoid prescribing by primary care small
      animal practices in England is provided. Clinic attended was a significant risk
      factor, indicating wide variation in prescribing patterns between clinics. A
      merged primary care veterinary clinical database was effective for
      epidemiological research.

PMID- 22417096
TI  - Causes of anaemia other than acute blood loss and their clinical significance in
      dogs.
AB  - OBJECTIVES: To identify the causes of anaemia, other than acute blood loss, in
      dogs and to determine whether severity of anaemia provides clues to the
      diagnosis. METHODS: The veterinary medical database of the Veterinary Campus
      Hospital, Lyon was searched. Dogs with anaemia (packed cell volume <37%) were
      included and assigned to different disease groups. Dogs with acute blood loss
      were excluded. The case records were examined for weakness at presentation, the
      severity and regeneration of anaemia and the final diagnosis including tumour
      type if applicable. RESULTS: The case records of 456 dogs with low packed cell
      volume were included. Cancer-related anaemia and anaemia of inflammatory disease
      accounted for 33.1 and 28.5% of cases, respectively. Most dogs with cancer
      related anaemia had solid tumours (73%). The prevalence of immune-mediated
      anaemia increased with severity of anaemia (5.3, 15.5, 41.2 and 56.2% for mild,
      moderate, severe and very severe anaemia, respectively), whereas the prevalence
      of anaemia of inflammatory disease decreased (36.7, 22.5, 2.9 and 0% for mild,
      moderate, severe and very severe anaemia, respectively). CLINICAL SIGNIFICANCE:
      Anaemia of inflammatory disease and cancer-related anaemia were the most
      frequently identified causes of anaemia in dogs. The percentage of dogs with
      immune-mediated anaemia increased with anaemia severity, whereas the percentage
      of dogs with anaemia of inflammatory disease decreased with anaemia severity.
      Thus, severity of anaemia may provide clues to the diagnosis.

PMID- 22417097
TI  - A prospective study of basal insulin concentrations in dogs with congenital
      portosystemic shunts.
AB  - OBJECTIVES: Hypoglycaemia is a common cause of morbidity in dogs with congenital
      portosystemic shunts but the aetiology is unknown. The hypothesis of this study
      was that dogs with congenital portosystemic shunts would have significantly
      higher insulin concentrations than dogs without congenital portosystemic shunts.
      The main objective of the study was to compare peripheral glucose and insulin
      concentrations between dogs with congenital portosystemic shunts and dogs without
      congenital portosystemic shunts. METHODS: Peripheral serum insulin and plasma
      glucose concentrations were measured in dogs with congenital portosystemic shunts
      and without congenital portosystemic shunts and compared both between groups as
      well as to reference intervals derived from healthy dogs. RESULTS: Congenital
      portosystemic shunts were diagnosed in 41 dogs. Forty-eight dogs hospitalised
      with other conditions acted as controls. Serum insulin concentrations were mildly
      elevated (A40 MUU/mL) in seven dogs and were markedly elevated in two dogs with
      congenital portosystemic shunts, yet mild hypoglycaemia (3.3 mmol/L) was detected
      in only one of these dogs. Four dogs with congenital portosystemic shunts showed
      fasting hypoglycaemia, yet insulin concentrations were within or below the
      reference interval in three. There was no difference between the median insulin
      concentration of dogs with congenital portosystemic shunts and without congenital
      portosystemic shunts. CLINICAL SIGNIFICANCE: Hyperinsulinaemia is infrequently
      observed in dogs with congenital portosystemic shunts. The aetiology of
      hypoglycaemia in dogs with congenital portosystemic shunts merits further
      investigation.

PMID- 22417098
TI  - Malignant peripheral nerve sheath tumour of the urinary bladder in a cat.
AB  - A 14-year-old domestic shorthair cat presented with a 5-month history of urinary
      incontinence and inappro-priate elimination. Ultrasonography revealed a well
      marginated, vascular mass of mixed echogenicity ex-tending from the dorsal wall
      of the urinary bladder into the lumen. Partial cystectomy was performed for re
      moval of the urinary bladder mass; histopathological evaluation revealed a
      spindle cell neoplasm with a prominent palisading pattern. Histomorphologic
      features and immunohistochemical demonstration of vimentin, glial fibrillary
      acidic protein and S-100 protein, combined with negativity for smooth muscle
      actin and desmin were consistent with malignant peripheral nerve sheath tumour.
      This case report describes a novel location of malignant peripheral nerve sheath
      tumour; to the authors' knowledge, the bladder has not been described as a site
      of origin in the cat or any other domestic species.

PMID- 22417102
TI  - Beneficial effects of calcium oral coadministration in gentamicin-induced
      nephrotoxicity in rats.
AB  - Frequent therapeutical use of an aminoglycoside antibiotic gentamicin (GM) is
      limited by its nephrotoxic effects often characterized by both morphological and
      functional alterations of kidney leading to acute renal failure. The aim of this
      study was to examine the effect of dietary calcium supplementation on GM-induced
      nephrotoxicity in rats. Experiments were performed on 30 adult male Wistar rats
      divided into three groups of 10 animals each. G-group received GM
      intraperitoneally at a dose of 100 mg/kg; GCa-group received the same dose of GM
      concomitantly with 1 g/kg calcium carbonate given orally; and C-group, serving as
      control, received 1 mL/day of normal saline. All groups were treated during 8
      consecutive days. Quantitative evaluation of GM-induced structural and functional
      changes of kidney was performed by histopathological, morphometrical, and
      biochemical analyses. Compared with control, G-group of rats were found to have
      diffusely and unequally thickened glomerular basement membrane with neutrophil
      cells infiltration. In addition, vacuolization of cytoplasm of proximal tubule
      cells with coagulation-type necrosis was observed. These GM-induced pathological
      lesions were significantly reduced in the rats of GCa-group. Morphometric
      analysis revealed statistically significant differences in the size of glomeruli
      (area, major and minor axes, perimeter), optical density, and roundness of
      glomeruli (p < 0.05) between G and GCa groups. Biochemical analysis showed
      significant elevation in blood urea and serum creatinine concentrations, whereas
      potassium concentration was lowered in G-group compared with the other groups (p
      < 0.01). It is concluded that oral supplementation of calcium during treatment
      with GM resulted in significant reduction of morphological and functional kidney
      alterations.

PMID- 22417104
TI  - Offline improvement in learning to read a novel orthography depends on direct
      letter instruction.
AB  - Improvement in performance after the end of the training session, termed "Offline
      improvement," has been shown in procedural learning tasks. We examined whether
      Offline improvement in learning a novel orthography depends on the type of
      reading instruction. Forty-eight adults received multisession training in reading
      nonsense words, written in an artificial script. Participants were trained in one
      of three conditions: alphabetical words preceded by direct letter instruction
      (Letter-Alph); alphabetical words with whole-word instruction (Word-Alph); and
      nonalphabetical (arbitrary) words with whole-word instruction (Word-Arb). Offline
      improvement was found only for the Letter-Alph group. Moreover, correlation with
      a standardized measure of word reading ability showed that good readers trained
      in the Letter-Alph group exhibit greater Offline improvement, whereas good
      readers trained in the Word-Arb group showed greater Within-session improvement
      during training. These results suggest that different consolidation processes and
      learning mechanisms were involved in each group. We argue that providing a short
      block of direct letter instruction prior to training resulted in increased
      involvement of procedural learning mechanisms during training.

PMID- 22417105
TI  - Epigenetic mechanisms as targets and companions of viral assaults.
AB  - The past decade has seen an explosion of interest for understanding epigenetic
      mechanisms. This is not surprising since it has been obvious that we need this
      knowledge to understand basic biology, such as cellular differentiation, stem
      cell maintenance, and pathological phenotype, etiology, and therapy responses. It
      is also evident that the constant exposure to the environment affects our
      functional genomes through epigenetic mechanisms. This short review will bring up
      general principles of epigenetic mechanisms as well as how viral infections,
      which constantly affect our physiology, can interphase with these in order to
      evade host defense and promote their own multiplication and/or latency.

PMID- 22417103
TI  - The retinoblastoma family of proteins and their regulatory functions in the
      mammalian cell division cycle.
AB  - The retinoblastoma (RB) family of proteins are found in organisms as distantly
      related as humans, plants, and insects. These proteins play a key role in
      regulating advancement of the cell division cycle from the G1 to S-phases. This
      is achieved through negative regulation of two important positive regulators of
      cell cycle entry, E2F transcription factors and cyclin dependent kinases. In
      growth arrested cells transcriptional activity by E2Fs is repressed by RB
      proteins. Stimulation of cell cycle entry by growth factor signaling leads to
      activation of cyclin dependent kinases. They in turn phosphorylate and inactivate
      the RB family proteins, leading to E2F activation and additional cyclin dependent
      kinase activity. This propels the cell cycle irreversibly forward leading to DNA
      synthesis. This review will focus on the basic biochemistry and cell biology
      governing the regulation and activity of mammalian RB family proteins in cell
      cycle control.

PMID- 22417106
TI  - Evolution of sexually transmitted and sexually transmissible human herpesviruses.
AB  - Herpesviruses occur in an impressively wide range of animals and are associated
      with various diseases. The numerous routes taken during hundreds of millions of
      years of evolution have contributed to their striking adaptability and success as
      pathogens. Herpesviruses share a distinct virion structure and are classified
      taxonomically into a single order, the Herpesvirales, which is divided into three
      families. The phylogenetic relationships among members of the most populous
      family, the Herpesviridae, which includes all nine human herpesviruses, are
      generally similar to those among their hosts, supporting the view that there has
      been a large degree of coevolution between virus and host. Three human
      herpesviruses (human cytomegalovirus, Kaposi's sarcoma-associated herpesvirus,
      and herpes simplex virus type 1) are classed as agents capable of sexually
      transmissible infection (StxI), and one (herpes simplex virus type 2) as an agent
      capable of sexually transmitted infection (STI). The evolutionary characteristics
      of these viruses are described.

PMID- 22417107
TI  - Scabies in animals and humans: history, evolutionary perspectives, and modern
      clinical management.
AB  - Scabies, a mite infestation frequently sexually transmitted, dates back to
      antiquity but remains a challenging parasite for study in clinical practice and
      community settings. Its history is one of centuries of slow progress to recognize
      the mite and to finally establish its nexus to the clinical syndrome of pruritis
      with several protean manifestations and different epidemiological patterns.
      Contemporary methods of management are briefly reviewed, with the future promise
      of improved evolutionary knowledge associated with the advent of molecular and
      genetic technology. Current information indicates that humans and earlier
      protohumans were most likely the source of animal scabies, first of dogs, and
      later of other species with subsequent spread to wildlife. Morphologically
      identical variants of Sarcoptes scabiei are nonetheless host specific, as
      determined by recent DNA studies, and invite future investigations into the
      dynamics of this troublesome sexually transmissible agent, with the goal of
      improved recognition and control.

PMID- 22417108
TI  - The evolution of Mycoplasma genitalium.
AB  - Mycoplasma genitalium is the smallest microorganism capable of self-replication.
      With its small genome, M. genitalium is the best representative of a minimal
      cell. The comparison of genome evolution among the three urogenital mycoplasmas,
      M. genitalium, M. hominis, and Ureaplasma parvum, not only indicated that they
      share a core genome of ~250 protein-encoding genes that correspond to their basic
      cell metabolism, but also showed a striking difference in their energy-generating
      pathways. M. genitalium is a sexually transmitted organism associated with
      nongonococcal urethritis in men and several inflammatory reproductive tract
      syndromes in women, such as cervicitis, pelvic inflammatory disease, and
      infertility. The treatment of M. genitalium infections has not yet been
      standardized. Macrolides are recommended, especially single-dose azithromycin;
      tetracyclines are responsible for a large number of therapeutic failures without
      any acquired resistance demonstrated. Acquired resistance to macrolides and
      fluoroquinolones leading to therapeutic failure has been described.

PMID- 22417109
TI  - DNA-hosted copper nanoclusters for fluorescent identification of single
      nucleotide polymorphisms.
AB  - Metal nanoclusters have received considerable interest due to their unique
      properties and potential applications in numerous fields. Particularly, newly
      emerging Cu nanoclusters offer excellent potential as functional biological
      probes. In this work, we for the first time report that the fluorescence of DNA
      hosted Cu nanoclusters is very sensitive to base type located in the major
      groove. This intriguing finding provides a sensitive fluorimetric diagnostic of
      the mismatch type in a specific DNA sequence, which is difficult to achieve by
      traditional methods. Furthermore, the research results have shed some light on
      the luminescent mechanism of Cu nanoclusters. Owing to its high specificity and
      easy operation without rigorously controlled temperature and arduous probe DNA
      design, it is expected that the proposed procedure can provide a tool for early
      diagnosis and risk assessment of malignancy.

PMID- 22417110
TI  - Laser beams interaction with polidocanol foam: molecular background.
AB  - OBJECTIVE: The goal of this study was to investigate the laser light scattering
      involved in the laser irradiation process of polidocanol foam samples. BACKGROUND
      DATA: Clinical experimental results proved that exposure of tissues impregnated
      with foaming polidocanol to laser radiation emitted at 1064 nm improved the
      efficacy of the treatment. Previous absorption studies on Aethoxysclerol 2%
      solution before and after exposure to Nd:YAG (1064 nm) laser beam have not shown
      important spectral modifications of it. MATERIALS AND METHODS: To achieve the
      purpose of this work, we produced polidocanol foam using the Tessari method. The
      batch was passed between the two syringes ~40 times. The resulting foam was
      stable for 5-6 min. A 10 mm optical cell containing the foam sample was
      introduced into a home-made Raman spectroscopy system, in which the laser
      radiation used to excite the Raman emission was the second harmonic (532 nm) of a
      pulsed Nd:YAG laser beam. The detection was made by a high resolution
      spectrograph and ICCD camera. RESULTS: The obtained Raman spectra were more
      intense in foam form than in simple solution. The laser light elastic scattering
      produced a larger optical path of the beam in the sample, and consequently, a
      larger absorption of it by the foam components that enhance the laser Raman
      scattering. CONCLUSIONS: The effect of the laser light may be expanded if the
      polidocanol is used as foam, because then the light scattering in the tissue
      becomes more important and the beam absorption becomes larger.

PMID- 22417111
TI  - Cervical smear photodiagnosis by fluorescence.
AB  - OBJECTIVE: Fluorescence is widely investigated and can characterize general
      changes occurring in the state of the cell and the tissue during physiological
      and/or pathological processes, but the method has not been adopted for clinical
      use. We present a photodiagnostic device and a relevant evaluation method fitted
      to classical screening procedures. This method is based on the discovery of smear
      content intrinsic fluorescent markers. BACKGROUND DATA: Meaningful spectral
      components of cervical smear samples differ from those measured in the entire
      live cervix. This article deals with the identification of changes in smear
      spectra in cervicitis and CIN2+ (cervical intraepithelial neoplasia of the second
      degree or higher) at 355 nm excitation. METHODS: Methods used in the study:
      microlaser-induced fluorescence spectroscopy of liquid cytology samples and
      histological evaluation of the biopsies of the same cervix (and/or only
      cytological evaluation) was performed for 78 cases. The fluorescence spectra of
      cervical cytology supernatant sediment were approximated with several Gaussian
      components. The ratios of the area under each Gaussian component to the whole
      area under the experimental curve were calculated and compared among histological
      groups by using the Mann-Whitney test and receiver operating characteristic (ROC)
      analysis. RESULTS: The results of this study are a concise summary of the
      essential features verified by the data: the spectral regions 402-416 nm and 424
      438 nm are important for the discrimination of both normal and CIN2+ groups (in
      terms of sensitivity, specificity, and positive predictive value). The spectral
      regions 480-515 nm and 595-625 nm are important for the identification of
      cervicitis. CONCLUSIONS: Cervical smear autofluorescence diagnostics could be
      useful for cancer screening at the point of care, in a simple cytology
      laboratory, and for the monitoring of treatment. We suggest possible fluorophores
      in the smear content.

PMID- 22417112
TI  - Genotoxicity, acute oral and dermal toxicity, eye and dermal irritation and
      corrosion and skin sensitisation evaluation of silver nanoparticles.
AB  - To clarify the health risks related to silver nanoparticles (Ag-NPs), we
      evaluated the genotoxicity, acute oral and dermal toxicity, eye irritation,
      dermal irritation and corrosion and skin sensitisation of commercially
      manufactured Ag-NPs according to the OECD test guidelines and GLP. The Ag-NPs
      were not found to induce genotoxicity in a bacterial reverse mutation test and
      chromosomal aberration test, although some cytotoxicity was observed. In acute
      oral and dermal toxicity tests using rats, none of the rats showed any abnormal
      signs or mortality at a dose level of ~ 2000 mg/kg. Similarly, acute eye and
      dermal irritation and corrosion tests using rabbits revealed no significant
      clinical signs or mortality and no acute irritation or corrosion reaction for the
      eyes and skin. In a skin sensitisation test using guinea pigs, one animal (1/20)
      showed discrete or patchy erythema, thus Ag-NPs can be classified as a weak skin
      sensitiser.

PMID- 22417113
TI  - Wegener's granulomatosis of the major salivary glands.
AB  - Wegener's granulomatosis is one of the anti-cytoplasmic autoantibodies (ANCA)
      associated vasculitides. Although it typically affects the lungs and kidneys, the
      head and neck are also involved in most cases but the site usually affected is
      the upper airway. However, there are 35 cases with well-documented
      clinicopathological data in which Wegener's granulomatosis manifested in the
      major salivary glands, most commonly the parotid. Twenty-four patients presented
      with salivary signs and symptoms, in eight of whom there was no other presenting
      manifestation. These signs and symptoms may mimic infection or neoplasia and
      laboratory investigations, including ANCA serology and histopathology, may be non
      specific; thus, in 21 of the 35 patients (60%) there was a delay in diagnosis.
      Amongst the 21 were 11 of the 14 (78.6%) patients who presented with unilateral
      parotid disease and three of the five who died. Three other patients suffered
      permanent pulmonary, two renal and five facial nerve damage. This article reviews
      the literature on major salivary gland involvement in Wegener's granulomatosis,
      which should be considered in the differential diagnosis of major salivary gland
      disease particularly if commoner causes have been excluded. A detailed medical
      history, and persistently inconclusive laboratory tests, could provide the clues
      that enable prompt diagnosis.

PMID- 22417115
TI  - Multiple biogeographical barriers identified across the monsoon tropics of
      northern Australia: phylogeographic analysis of the brachyotis group of rock
      wallabies.
AB  - The monsoon tropics of northern Australia are a globally significant biodiversity
      hotspot, but its phylogeography is poorly known. A major challenge for this
      region is to understand the biogeographical processes that have shaped the
      distribution and diversity of taxa, without detailed knowledge of past climatic
      and environmental fluctuations. Although molecular data have great potential to
      address these questions, only a few species have been examined
      phylogeographically. Here, we use the widely distributed and abundant short-eared
      rock-wallaby (Petrogale brachyotis; n = 101), together with the sympatric monjon
      (P. burbidgei; n = 11) and nabarlek (P. concinna; n = 1), to assess historical
      evolutionary and biogeographical processes in northern Australia. We sequenced
      ~1000 bp of mitochondrial DNA (control region, ND2) and ~3000 bp of nDNA (BRCA1,
      omega-globin and two anonymous loci) to investigate phylogeographic structuring
      and delineate the time-scale of diversification within the region. Our results
      indicate multiple barriers between the Top End (Northern Territory) and Kimberley
      (Western Australia), which have caused divergence throughout the Plio
      Pleistocene. Eight geographically discrete and genetically distinct lineages
      within the brachyotis group were identified, five of which are separated by major
      river valleys (Ord, Victoria, Daly), arid lowlands and discontinuous sandstone
      ranges. It is likely that these barriers have similarly influenced genetic
      structure in other monsoonal biota.

PMID- 22417114
TI  - Revised classification/nomenclature of vitiligo and related issues: the Vitiligo
      Global Issues Consensus Conference.
AB  - During the 2011 International Pigment Cell Conference (IPCC), the Vitiligo
      European Taskforce (VETF) convened a consensus conference on issues of global
      importance for vitiligo clinical research. As suggested by an international panel
      of experts, the conference focused on four topics: classification and
      nomenclature; definition of stable disease; definition of Koebner's phenomenon
      (KP); and 'autoimmune vitiligo'. These topics were discussed in seven working
      groups representing different geographical regions. A consensus emerged that
      segmental vitiligo be classified separately from all other forms of vitiligo and
      that the term 'vitiligo' be used as an umbrella term for all non-segmental forms
      of vitiligo, including 'mixed vitiligo' in which segmental and non-segmental
      vitiligo are combined and which is considered a subgroup of vitiligo. Further,
      the conference recommends that disease stability be best assessed based on the
      stability of individual lesions rather than the overall stability of the disease
      as the latter is difficult to define precisely and reliably. The conference also
      endorsed the classification of KP for vitiligo as proposed by the VETF (history
      based, clinical observation based, or experimentally induced). Lastly, the
      conference agreed that 'autoimmune vitiligo' should not be used as a separate
      classification as published evidence indicates that the pathophysiology of all
      forms of vitiligo likely involves autoimmune or inflammatory mechanisms.

PMID- 22417116
TI  - Development and initial validity of the Object Relations Rating Scale.
AB  - The aim of this study was to report on the development and the initial validation
      of the Object Relations Rating Scale (ORRS), which is a measure of in-session
      enactments of object relations that draws on a psychodynamic conceptualization of
      personality organization. Forty participants were included in the study,
      distributed among neurotic, borderline and psychotic personality organizations
      (PO). Results showed that the interrater reliability of this new measure is good.
      Two tests of criterion validity support the validity of the measure: the ORRS
      discriminates well between the three PO groups and it correlates in expected ways
      with five PO dimensions. Finally, ORRS scales that pertain to the degree of in
      session object relation enactments correlated with a measure of transference
      intensity (convergent validity), and correlations with therapists experience were
      low as expected (discriminant validity).

PMID- 22417117
TI  - Variable abnormal physiological motility in the proximal upper gastrointestinal
      tract in gastroparesis.
AB  - BACKGROUND: Traditional testing for gastroparesis with gastric emptying
      scintigraphy (GES) likely misses a subset of patients because of the
      heterogeneous nature of the disease. The primary aim of this study is to
      determine the prevalence of simultaneously measured transit and pressure
      abnormalities in patients with gastroparesis. The secondary aim is to assess
      diagnostic gain realized by measuring antroduodenal pressure and gastric transit
      with wireless motility capsule (WMC) compared to gastric transit measured by GES.
      Identification of abnormalities beyond gastric transit delay in gastroparesis may
      yield novel targets for pharmacological therapies. METHODS: Forty-three subjects
      with symptoms of gastroparesis and previous abnormal GES within 2 years were
      enrolled in the study. Subjects underwent simultaneous GES and WMC to assess
      gastric transit. Gastric and small bowel pressure profiles were measured by WMC
      to determine the contribution of pressure to diagnostic gain realized with WMC.
      KEY RESULTS: Fifty-one percent of subjects had abnormal GES while 70% of subjects
      had either abnormal gastric emptying time (GET) or antroduodenal pressure.
      Gastric emptying time was abnormal in 60% of subjects while gastric or small
      bowel pressure was abnormal in 47% of subjects. The overall diagnostic gain of
      WMC compared to GES was 19% (P = 0.04). Seven percent of subjects had abnormal
      small bowel pressure profiles when both GES and GET were normal. CONCLUSIONS &
      INFERENCES: (i) Gastroparesis is a heterogeneous disorder and testing only solid
      food emptying by scintigraphy may miss a significant amount of pathology. (ii)
      Measuring complementary aspects of gastric and small bowel function
      simultaneously results in greater detection of physiologic abnormalities that may
      underlie patient symptoms.

PMID- 22417118
TI  - Elephantiatic dermopathy.

PMID- 22417119
TI  - Renal haemorrhage risk after extracorporeal shockwave lithotripsy: results from
      the Japanese Diagnosis Procedure Combination Database.
AB  - OBJECTIVE: To assess clinical and mechanical risk factors of clinically
      significant renal haemorrhage after extracorporeal shock wave lithotripsy (ESWL).
      PATIENTS AND METHODS: Patient data were extracted from the Diagnosis Procedure
      Combination (DPC) database from 6 months per each year, 2006-2008. The
      availability of lithotripters in each hospital was identified. We performed
      logistic regression analysis, which included the generator type
      (electrohydraulic, electromagnetic or piezoelectric), age, gender, laterality of
      stones (right, left or uncertain), location of stones (kidney, ureter or
      uncertain), total number of treatment sessions, anaesthesia and hospital volume
      (HV), focal size (greater or less than 400 mm(3)) and F2 angle (greater or less
      than 70 degrees ). Renal haemorrhage events were identified within the database.
      RESULTS: Overall, 81 renal haemorrhage events in 26,969 patients (32,476 ESWL
      sessions) at 482 hospitals with 38 lithotripter models were identified. The
      incidence of events was 0.50% with renal stones and 0.14% with ureter stones.
      Specifications of 34 lithotripter models were available. Use of piezoelectric
      lithotripters (vs electromagnettic, OR 0.13, P = 0.044) and high HV (>=140/year,
      vs <=70/year, OR 0.49, P = 0.012) significantly decreased the risk of renal
      haemorrhage events. Age, gender, focal size and F2 angle did not show statistical
      significance. CONCLUSION: There is a low incidence of renal haemorrhage after
      ESWL. The less invasive nature of piezoelectric lithotripters and an inverse
      volume-outcome relationship with ESWL procedures was revealed. Age, focal size
      and F2 angle do not appear to have a significant impact on renal haemorrhage.

PMID- 22417120
TI  - Novel analysis of cation solvation using a graph theoretic approach.
AB  - A new method for analyzing molecular dynamics simulation data is employed to
      study the solvent shell structure and exchange processes of mono-, di-, and
      trivalent metal cations in water. The instantaneous coordination environment is
      characterized in terms of the coordinating waters' H-bonding network,
      orientations, mean residence times, and the polyhedral configuration. The graph
      theory-based algorithm provides a rapid frame-by-frame identification of
      polyhedra and reveals fluctuations in the solvation shell shape--previously
      unexplored dynamic behavior that in many cases can be associated with the
      exchange reactions of water between the first and second solvation shells.
      Extended solvation structure is also analyzed graphically, revealing details of
      the hydrogen bonding network that have practical implications for connecting
      molecular dynamics data to ab initio cluster calculations. Although the
      individual analyses of water orientation, residence time, etc., are commonplace
      in the literature, their combination with graphical algorithms is new and
      provides added chemical insight.

PMID- 22417121
TI  - The magnitude of hydraulic redistribution by plant roots: a review and synthesis
      of empirical and modeling studies.
AB  - Hydraulic redistribution (HR) - the movement of water from moist to dry soil
      through plant roots - occurs worldwide within a range of different ecosystems and
      plant species. The proposed ecological and hydrologic impacts of HR include
      increasing dry-season transpiration and photosynthetic rates, prolonging the life
      span of fine roots and maintaining root-soil contact in dry soils, and moving
      rainwater down into deeper soil layers where it does not evaporate. In this
      review, we compile estimates of the magnitude of HR from ecosystems around the
      world, using representative empirical and modeling studies from which we could
      extract amounts of water redistributed by plant root systems. The reported
      average magnitude of HR varies by nearly two orders of magnitude across
      ecosystems, from 0.04 to 1.3 mm H(2)O d(-1) in the empirical literature, and from
      0.1 to 3.23 mm H(2)O d(-1) in the modeling literature. Using these synthesized
      data, along with other published studies, we examine this variation in the
      magnitude of upward and downward HR, considering effects of plant, soil and
      ecosystem characteristics, as well as effects of methodological details (in both
      empirical and modeling studies) on estimates of HR. We take both ecological and
      hydrologic perspectives.

PMID- 22417122
TI  - Anti-inflammatory effect of three iridoids in human neutrophils.
AB  - To verify the anti-inflammatory potency of iridoids, three iridoids (two natural,
      loganic acid: LA; geniposide: GE; and an artefact, 7(S)-n-butyl morroniside: BM)
      were investigated in vitro on the inhibition of superoxide generation in human
      neutrophils. All compounds showed inhibitory effect on fMLP-induced superoxide
      generation in a concentration-dependent manner with the following order:
      BM>LA>GE. BM exhibits potent inhibitory activity on superoxide anion induced by
      PMA, while LA and GE showed weak effect. When AA was used as stimulus, the
      generation of superoxide anion was suppressed by BM in a concentration-dependent
      manner. LA and GE exhibit both sides effect on superoxide generation.

PMID- 22417123
TI  - Determinants of under-five mortality in rural and urban Kenya.
AB  - INTRODUCTION: The disparity in under-five year-old mortality rates between rural
      and urban areas in Kenya (also reported in other in sub-Saharan African
      countries), is a critical national concern. The objective of this study was to
      investigate the influence of geographical location and maternal factors on the
      likelihood of mortality among under-five children in rural and urban areas in
      Kenya. METHODS: Data from the 2008-2009 Kenya Demographic and Health Survey were
      used to determine mortality among under-five children (n=16,162) in rural and
      urban areas in the 5 years preceding the survey. Multivariate analysis was used
      to compare the influence of key risk factors in rural and urban areas. RESULTS:
      Overall, the likelihood of death among under-five children in the rural areas was
      significantly higher than that in the urban areas (p<0.05). Household poverty was
      a key predictor for mortality in the rural areas, but the influence of
      breastfeeding was similar in the two areas. The likelihood of under-five
      mortality was significantly higher in the rural areas of Coast, Nyanza and
      Western Provinces than in Central Province. CONCLUSIONS: The study shows that the
      determinants of under-five mortality differ in rural and urban areas in Kenya.
      Innovative and targeted strategies are required to address rural poverty and
      province-specific sociocultural factors in order to improve child survival in
      rural Kenya.

PMID- 22417124
TI  - Rapid size-controlled synthesis of dextran-coated, 64Cu-doped iron oxide
      nanoparticles.
AB  - Research into developing dual modality probes enabled for magnetic resonance
      imaging (MRI) and positron emission tomography (PET) has been on the rise
      recently due to the potential to combine the high resolution of MRI and the high
      sensitivity of PET. Current synthesis techniques for developing multimodal probes
      is largely hindered in part by prolonged reaction times during radioisotope
      incorporation--leading to a weakening of the radioactivity. Along with a time
      efficient synthesis, the resulting products must fit within a critical size range
      (between 20 and 100 nm) to increase blood retention time. In this work, we
      describe a novel, rapid, microwave-based synthesis technique to grow dextran
      coated iron oxide nanoparticles doped with copper (DIO/Cu). Traditional methods
      for coprecipitation of dextran-coated iron oxide nanoparticles require refluxing
      for 2 h and result in approximately 50 nm diameter particles. We demonstrate that
      microwave synthesis can produce 50 nm nanoparticles with 5 min of heating. We
      discuss the various parameters used in the microwave synthesis protocol to vary
      the size distribution of DIO/Cu and demonstrate the successful incorporation of
      (64)Cu into these particles with the aim of future use for dual-mode MR/PET
      imaging.

PMID- 22417125
TI  - lemmingA encodes the Apc11 subunit of the APC/C in Drosophila melanogaster that
      forms a ternary complex with the E2-C type ubiquitin conjugating enzyme, Vihar
      and Morula/Apc2.
AB  - BACKGROUND: Ubiquitin-dependent protein degradation is a critical step in key
      cell cycle events, such as metaphase-anaphase transition and mitotic exit. The
      anaphase promoting complex/cyclosome (APC/C) plays a pivotal role in these
      transitions by recognizing and marking regulatory proteins for proteasomal
      degradation. Its overall structure and function has been elucidated mostly in
      yeasts and mammalian cell lines. The APC/C is, however, a multisubunit assembly
      with at least 13 subunits and their function and interaction within the complex
      is still relatively uncharacterized, particularly in metazoan systems. Here,
      lemming (lmg) mutants were used to study the APC/C subunit, Apc11, and its
      interaction partners in Drosophila melanogaster. RESULTS: The lmg gene was
      initially identified through a pharate adult lethal P element insertion mutation
      expressing developmental abnormalities and widespread apoptosis in larval
      imaginal discs and pupal abdominal histoblasts. Larval neuroblasts were observed
      to arrest mitosis in a metaphase-like state with highly condensed, scattered
      chromosomes and frequent polyploidy. These neuroblasts contain high levels of
      both cyclin A and cyclin B. The lmg gene was cloned by virtue of the lmg03424 P
      element insertion which is located in the 5' untranslated region. The lemming
      locus is transcribed to give a 2.0 kb mRNA that contains two ORFs, lmgA and lmgB.
      The lmgA ORF codes for a putative protein with more than 80% sequence homology to
      the APC11 subunit of the human APC/C. The 85 amino acid protein also contains a
      RING-finger motif characteristic of known APC11 subunits. The lmgA ORF alone was
      sufficient to rescue the lethal and mitotic phenotypes of the lmg138 null allele
      and to complement the temperature sensitive lethal phenotype of the APC11-myc9
      budding yeast mutant. The LmgA protein interacts with Mr/Apc2, and they together
      form a binding site for Vihar, the E2-C type ubiquitin conjugating enzyme.
      Despite being conserved among Drosophila species, the LmgB protein is not
      required for viability or fertility. CONCLUSIONS: Our work provides insight into
      the subunit structure of the Drosophila APC/C with implications for its function.
      Based on the presented data, we suggest that the Lmg/Apc11 subunit recruits the
      E2-C type ubiquitin conjugating enzyme, Vihar, to the APC/C together with Mr/Apc2
      by forming a ternary complex.

PMID- 22417126
TI  - Fibrillary glomerulonephritis associated with Behcet's syndrome.
AB  - Fibrillary glomerulonephritis (FGN) is a rare cause of progressive renal
      dysfunction resulting in fibrillary deposits in the mesangium and/or glomerular
      basement membrane (GBM). Some case reports have shown FGN in patients with
      rheumatoid arthritis and other autoimmune diseases. This is the first case report
      of FGN in a patient with Behcet's syndrome. The most common renal histological
      finding in Behcet's syndrome is secondary amyloidosis. A 46-year-old woman with a
      4-year history of Behcet's syndrome was referred to the nephrology clinic with
      foamy urine with non-selective proteinuria (urine protein-to-creatinine ratio was
      1400 mg protein/g creatinine) and microscopic hematuria. Serum and urine protein
      electrophoresis showed no evidence of monoclonal gammopathy. A renal biopsy was
      performed. Light microscopy showed mesangial widening and nodular expansion with
      hyaline deposits. Immunofluorescence microscopy revealed immunoglobulin M
      deposits in the mesangium. Congo red staining was negative. Electron microscopy
      showed fibrillary deposits on the GBM. Pathological findings were consistent with
      FGN. She had been taking 50 mg azathioprine and 3000 mg mesalazine per day for 4
      years due to Behcet's syndrome, so we did not add any other immunosuppressive
      agents or corticosteroids. Treatment of this glomerulopathy is not promising. It
      has been noted that none of the various approaches, including corticosteroid,
      plasmapheresis, and cytotoxic therapy, improves prognosis.

PMID- 22417127
TI  - Progressive decline of residual follicle pool after clinical diagnosis of
      autoimmune ovarian insufficiency.
AB  - CONTEXT: In approximately 5-8% patients with primary ovarian insufficiency (POI),
      the disease is caused by an autoimmune process made evident by the appearance of
      autoantibodies against steroidogenic enzymes (SCA-POI). Anti-mullerian hormone
      (AMH) is the best marker of the residual follicular pool. OBJECTIVE: To evaluate
      the rate of loss of the residual follicle pool in women with SCA-POI after
      clinical diagnosis. DESIGN AND METHODS: One hundred and thirty-two women with POI
      were tested for 21-hydroxylase autoantibodies, 17alpha-hydroxylase autoantibodies
      and P450scc autoantibodies, and 35 patients with SCA-POI were identified. AMH was
      analysed at the time of the first visit in all women with POI, and in follow-up,
      serum samples were taken 1-3 years after in 11 women with SCA-POI and detectable
      AMH. RESULTS: 12/35 (35%) women with SCA-POI had AMH levels within the normal
      range at the time of first sampling, as compared to 6/97 (6%) with idiopathic POI
      (P < 0.001). 11/17 (65%) women with SCA-POI with <6 years disease duration had
      normal serum AMH concentration. A progressive decline in AMH concentration was
      observed at longitudinal follow-up in all 11 AMH-positive women with SCA-POI, at
      an estimated average rate of 1.6 MUg/l AMH/year (corresponding to an average 57%
      of preserved follicle pool/previous year) (R(2)  = 0.219, P = 0.028). After 6
      years of disease duration, only 1/18 (6%) women with SCA-POI had detectable
      levels of AMH, similar to women with idiopathic POI (5/78, 6%). CONCLUSION: Most
      women with SCA-POI present at clinical diagnosis with a preserved follicle pool
      that is progressively lost within a few years.

PMID- 22417128
TI  - A SAR study of novel antiproliferative ruthenium and osmium complexes with
      quinoxalinone ligands in human cancer cell lines.
AB  - A series of ruthenium(II) arene complexes with 3-(1H-benzimidazol-2-yl)-1H
      quinoxalin-2-one, bearing pharmacophoric groups of known protein kinase
      inhibitors, and related benzoxazole and benzothiazole derivatives have been
      synthesized. In addition, the corresponding osmium complexes of the unsubstituted
      ligands have also been prepared. The compounds have been characterized by NMR, UV
      vis, and IR spectroscopy, ESI mass spectrometry, elemental analysis, and by X-ray
      crystallography. Antiproliferative activity in three human cancer cell lines
      (A549, CH1, SW480) was determined by MTT assays, yielding IC(50) values of 6-60
      MUM for three unsubstituted metal-free ligands, whereas values for the metal
      complexes vary in a broad range from 0.3 to 140 MUM. Complexation with osmium of
      quinoxalinone derivatives with benzimidazole or benzothiazole results in a more
      consistent increase in cytotoxicity than complexation with ruthenium. For
      selected compounds, the capacity to induce apoptosis was confirmed by
      fluorescence microscopy and flow-cytometric analysis, whereas cell cycle effects
      are only moderate.

PMID- 22417129
TI  - Geographical structure and adaptive population differentiation in herbivore
      defence genes in European aspen (Populus tremula L., Salicaceae).
AB  - When a phenotypic trait is subjected to spatially variable selection and local
      adaptation, the underlying genes controlling the trait are also expected to show
      strong patterns of genetic differentiation because alternative alleles are
      favoured in different geographical locations. Here, we study 71 single nucleotide
      polymorphisms (SNPs) from seven genes associated with inducible defence responses
      in a sample of Populus tremula collected from across Sweden. Four of these genes
      (PPO2, TI2, TI4 and TI5) show substantial population differentiation, and a
      principal component analyses conducted on the defence SNPs divides the Swedish
      population into three distinct clusters. Several defence SNPs show latitudinal
      clines, although these were not robust to multiple testing. However, five SNPs
      (located within TI4 and TI5) show strong longitudinal clines that remain
      significant after multiple test correction. Genetic geographical variation,
      supporting local adaptation, has earlier been confirmed in genes involved in the
      photoperiod pathway in P. tremula, but this is, to our knowledge, one of the
      first times that geographical variation has been found in genes involved in plant
      defence against antagonists.

PMID- 22417130
TI  - Heme oxygenase-1 modulates thrombomodulin and activated protein C levels to
      attenuate lung injury in cecal ligation and puncture-induced acute lung injury
      mice.
AB  - Acute lung injury (ALI) is often associated with sepsis and is the most common
      cause of acute respiratory failure. The authors evaluated the role of the heme
      oxygenase (HO)/carbon monoxide (CO) system on lung injury in a cecal ligation and
      puncture (CLP)-induced mouse model of ALI. The authors established CLP-induced
      ALI in C57BL/6 mice. They pretreated CLP-induced mice with HO-1 inducer (hemin)
      or HO-1 inhibitor (Zn protoporphyrin [Znpp]) and determined various lung injury
      parameters including partial pressure of arterial oxygen, thrombosis, edema, and
      plasma malondialdehyde (MDA), and myeloperoxidase (MPO) level. Enzyme-linked
      immunosorbent assay (ELISA) was performed to measure plasma thrombomodulin (TM)
      and activated protein C (APC) levels. TM and HO-1 expression in lung tissue was
      evaluated by immunofluorescence staining and Western blotting. Survival rate was
      also monitored. CLP-induced ALI was associated with decreased partial pressure of
      arterial oxygen, and increased thrombosis, edema, and plasma MDA, and MPO level.
      Plasma TM was significantly up-regulated, whereas cell surface TM in lung tissue
      was significantly decreased in the CLP group compared to the sham animals.
      Pretreatment with hemin caused up-regulation of HO-1 expression and improved
      partial pressure of arterial oxygen. Hemin pretreatment also caused a significant
      decrease in plasma TM along with increased cell surface TM expression in lung
      tissue, suggesting attenuation of lung injury. Survival data showed that no
      difference for survival between CLP animals pretreated with hemin or Znpp. Taken
      together, HO-1 exerts its protective effects on CLP-induced ALI via regulating
      cell surface TM and APC expression and modulating blood coagulation.

PMID- 22417131
TI  - Is treatment in a day hospital step-down program superior to outpatient
      individual psychotherapy for patients with personality disorders? 36 months
      follow-up of a randomized clinical trial comparing different treatment
      modalities.
AB  - Despite increasing interest in the development of effective treatments for
      patients with PDs, there is still no consensus about the optimal treatment
      setting for this group of patients. This study reports the 36 months follow-up of
      the Ulleval Personality Project (UPP) (n=113), a randomized clinical trial
      comparing two treatment modalities for patients with PDs: an intensive long-term
      step-down treatment program, consisting of short-term day hospital treatment
      followed by combined group and individual psychotherapy organized in a hospital
      setting, with "ordinary" outpatient individual psychotherapy in private practice
      for patients with moderate to severe PDs. Patients in both treatment groups
      showed improvements in several clinical measures after 36 months. However,
      contrary to our expectations, patients in the outpatient treatment setting
      improved significantly more. Possible explanations for this surprising finding
      are discussed. The study cannot exclude the possibility that treatment aspects
      other than differences in modalities could explain some of the differential
      effectiveness (e.g. differences between therapists).

PMID- 22417132
TI  - Combined cytoplasmic and membranous EGFR and p53 overexpression is a poor
      prognostic marker in early stage oral squamous cell carcinoma.
AB  - OBJECTIVE: Our aim was to evaluate the expression of several molecules that
      regulate growth, the cell cycle and signalling pathways including EGFR, p53, p16
      and p27 in oral squamous cell carcinomas (OSCC). We examined their utility as
      prognostic markers by relating to clinicopathological characteristics and the
      clinical outcome. PATIENTS AND METHODS: Using tissue microarray technology, we
      analysed 67 primary OSCC and examined immunohistochemical expression of EGFR,
      p53, p16 and p27. Multivariate analysis was conducted to examine their role in
      survival. RESULTS: Many of the markers were highly expressed in these cancers.
      Membranous EGFR expression in 95.2%, both membrane and cytoplasm expression in
      35%, p53 expression in 61.6%, p27 expression in 89.5% and p16 expression in 27.9%
      of cases. In the multivariate analysis, independent prognostic influence of a
      lower overall survival was determined only for advanced tumour stage (P < 0.001),
      p53 overexpression (P = 0.004), EGFR cytoplasm and membrane co-expression
      location (P = 0.002) and p16 reduced expression (P = 0.002). When considering a
      subgroup of early stage tumours, p53 overexpression (P = 0.028) and combined
      membranous and cytoplasm EGFR co-expression (P = 0.039) were indicators of a
      lower overall survival. For disease-free survival, in addition to these three
      factors, the histological grade (P = 0.011) showed independent prognostic values.
      CONCLUSION: The independent value of EGFR subcellular location (cytoplasm and
      membrane) and p53 overexpression in overall survival even in early stages of OSCC
      suggests that these markers may serve as reliable biological markers to identify
      high-risk subgroups and to guide therapy.

PMID- 22417134
TI  - Response to Mayers and Redick: "clinical utility of ImPACT assessment for
      postconcussion return-to-play counseling: psychometric issues".

PMID- 22417133
TI  - Triple stimulus-responsive polypeptide nanoparticles that enhance intratumoral
      spatial distribution.
AB  - To address the limited tumor penetration of nanoparticle drug delivery vehicles,
      we report the first pH-responsive polypeptide micelle that dissociates at the low
      extracellular pH of solid tumors. This histidine-rich elastin-like polypeptide
      block copolymer self-assembles at 37  degrees C into spherical micelles that are
      stabilized by Zn(2+) and are disrupted as the pH drops from 7.4 to 6.4. These pH
      sensitive micelles demonstrate better in vivo penetration and distribution in
      tumors than a pH-insensitive control.

PMID- 22417135
TI  - Suspected rapid-onset neutropenia following etanercept use: disproved following
      rechallenge and lessons to be learned.

PMID- 22417136
TI  - Follicular vitiligo: a new form of vitiligo.

PMID- 22417137
TI  - The effect of Phase 2 of the Premier Hospital Quality Incentive Demonstration on
      incentive payments to hospitals caring for disadvantaged patients.
AB  - OBJECTIVE: The Medicare and Premier Inc. Hospital Quality Incentive Demonstration
      (HQID), a hospital-based pay-for-performance program, changed its incentive
      design from one rewarding only high performance (Phase 1) to another rewarding
      high performance, moderate performance, and improvement (Phase 2). We tested
      whether this design change reduced the gap in incentive payments among hospitals
      treating patients across the gradient of socioeconomic disadvantage. DATA: To
      estimate incentive payments in both phases, we used data from the Premier Inc.
      website and from Medicare Provider Analysis and Review files. We used data from
      the American Hospital Association Annual Survey and Centers for Medicare and
      Medicaid Services Impact File to identify hospital characteristics. STUDY DESIGN:
      Hospitals were divided into quartiles based on their Disproportionate Share Index
      (DSH), from lowest disadvantage (Quartile 1) to highest disadvantage (Quartile
      4). In both phases of the HQID, we tested for differences across the DSH
      quartiles for three outcomes: (1) receipt of any incentive payments; (2) total
      incentive payments; and (3) incentive payments per discharge. For each of the
      study outcomes, we performed a hospital-level difference-in-differences analysis
      to test whether the gap between Quartile 1 and the other quartiles decreased from
      Phase 1 to Phase 2. PRINCIPAL FINDINGS: In Phase 1, there were significant gaps
      across the DSH quartiles for the receipt of any payment and for payment per
      discharge. In Phase 2, the gap was not significant for the receipt of any
      payment, but it remained significant for payment per discharge. For the receipt
      of any incentive payment, difference-in-difference estimates showed significant
      reductions in the gap between Quartile 1 and the other quartiles (Quartile 2,
      17.5 percentage points [p < .05]; Quartile 3, 18.1 percentage points [p < .01];
      Quartile 4, 28.3 percentage points [p < .01]). For payments per discharge, the
      gap was also significantly reduced between Quartile 1 and the other quartiles
      (Quartile 2, $14.92 per discharge [p < .10]; Quartile 3, $17.34 per discharge [p
      < .05]; Quartile 4, $21.31 per discharge [p < .01]). There were no significant
      reductions in the gap for total payments. CONCLUSIONS: The design change in the
      HQID reduced the disparity in the receipt of any incentive payment and for
      incentive payments per discharge between hospitals caring for the most and least
      socioeconomically disadvantaged patient populations.

PMID- 22417138
TI  - Obesity: a disease or a biological adaptation? An update.
AB  - Obesity is characterized by the accumulation of excess body fat and can be
      conceptualized as the physical manifestation of chronic energy excess. An
      important challenge of today's world is that our so-called obesogenic environment
      is conducive to the consumption of energy and unfavourable to the expenditure of
      energy. The modern, computer-dependent, sleep-deprived, physically inactive
      humans live chronically stressed in a society of food abundance. From a
      physiological standpoint, the excess weight gain observed in prone individuals is
      perceived as a normal consequence to a changed environment rather than a
      pathological process. In other words, weight gain is a sign of our contemporary
      way of living or a 'collateral damage' in the physiological struggle against
      modernity. Additionally, substantial body fat loss can complicate appetite
      control, decrease energy expenditure to a greater extent than predicted, increase
      the proneness to hypoglycaemia and its related risk towards depressive symptoms,
      increase the plasma and tissue levels of persistent organic pollutants that
      promote hormone disruption and metabolic complications, all of which are
      adaptations that can increase the risk of weight regain. In contrast, body fat
      gain generally provides the opposite adaptations, emphasizing that obesity may
      realistically be perceived as an a priori biological adaptation for most
      individuals. Accordingly, prevention and treatment strategies for obesity should
      ideally target the main drivers or root causes of body fat gain in order to be
      able to improve the health of the population.

PMID- 22417139
TI  - Fitting multimeric protein complexes into electron microscopy maps using 3D
      Zernike descriptors.
AB  - A novel computational method for fitting high-resolution structures of multiple
      proteins into a cryoelectron microscopy map is presented. The method named
      EMLZerD generates a pool of candidate multiple protein docking conformations of
      component proteins, which are later compared with a provided electron microscopy
      (EM) density map to select the ones that fit well into the EM map. The comparison
      of docking conformations and the EM map is performed using the 3D Zernike
      descriptor (3DZD), a mathematical series expansion of three-dimensional
      functions. The 3DZD provides a unified representation of the surface shape of
      multimeric protein complex models and EM maps, which allows a convenient, fast
      quantitative comparison of the three-dimensional structural data. Out of 19
      multimeric complexes tested, near native complex structures with a root-mean
      square deviation of less than 2.5 A were obtained for 14 cases while medium range
      resolution structures with correct topology were computed for the additional 5
      cases.

PMID- 22417142
TI  - Is MMP-7 gene polymorphism a possible risk factor for chronic obstructive
      pulmonary disease in Turkish patients.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease
      that leads to fixed narrowing of small airways and alveolar wall destruction
      (emphysema). This study was performed to test the association between MMP-7
      (rs155668818) and MMP-12 (rs56184183) polymorphisms in the MMP-7 gene and COPD
      risk and its severity in the Turkish population. MMP-7 and MMP-12 polymorphisms
      were genotyped in 85 patients with COPD and 73 healthy control subjects using
      real-time polymerase chain reaction analysis. There were significant differences
      in the distribution of MMP-7 genotypes but not in the frequencies of these
      alleles between COPD patients and controls (p=0.009, p=0.102, respectively). The
      MMP-7 AA genotype was found to be associated with an increased risk of COPD
      (p=0.004; odds ratio: 2.576; confidence interval: 1.297-5.119). The lowest values
      of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC
      in patients with GG homozygosity were determined and these values were
      statistically significant compared to the control subjects (p<0.001, p<0.001,
      p<0.001). When the present study groups were analyzed for MMP-12 polymorphism, it
      was found that all the subjects had wild-type genotype for this polymorphism.
      These findings have suggested that MMP-7 polymorphism might be associated with
      the risk and progression of COPD in the Turkish population.

PMID- 22417141
TI  - Lipofuscin and A2E accumulate with age in the retinal pigment epithelium of Nrl-/
      mice.
AB  - Lipofuscin is a fluorescent material with significant phototoxic potential that
      accumulates with age in the retinal pigment epithelium (RPE) of the eye. It is
      thought to be a factor in retinal degeneration diseases. The most extensively
      characterized lipofuscin component, N-retinylidene-N-retinylethanolamine (A2E),
      has been proposed to be a byproduct of reactions involving the visual pigment
      chromophore. To examine the impact of the visual pigment and photoreceptor cell
      type on lipofuscin accumulation, we analyzed the RPE from Nrl(-/-) mice of
      various ages for lipofuscin fluorescence and A2E levels. The photoreceptor cells
      of the Nrl(-/-) retina contain only cone-like pigments, and produce cone-like
      responses to photostimulation. The cone-like nature of these cells was confirmed
      by the presence of RPE65. Lipofuscin was measured with fluorescence imaging,
      whereas A2E was quantified by UV/VIS absorbance spectroscopy coupled to HPLC. The
      identity of A2E was corroborated with tandem mass spectrometry. Lipofuscin and
      A2E accumulated with age, albeit to lower levels compared with wild type mice.
      The emission spectra of RPE lipofuscin granules from Nrl(-/-) mice were similar
      to those from wild type mice, with lambda(max) ca 610 nm. These results
      demonstrate that cone visual pigments can contribute to the production of
      lipofuscin and A2E.

PMID- 22417143
TI  - Facing the sunrise: cultural worldview underlying intrinsic-based encoding of
      absolute frames of reference in aymara.
AB  - The Aymara of the Andes use absolute (cardinal) frames of reference for
      describing the relative position of ordinary objects. However, rather than
      encoding them in available absolute lexemes, they do it in lexemes that are
      intrinsic to the body: nayra ("front") and qhipa ("back"), denoting east and
      west, respectively. Why? We use different but complementary ethnographic methods
      to investigate the nature of this encoding: (a) linguistic expressions and speech
      gesture co-production, (b) linguistic patterns in the distinct regional Spanish
      based variety Castellano Andino (CA), (c) metaphorical extensions of CA's spatial
      patterns to temporal ones, and (d) layouts of traditional houses. Findings
      indicate that, following fundamental principles of Aymara cosmology, people,
      objects, and land--as a whole--are conceived as having an implicit canonical
      orientation facing east, a primary landmark determined by the sunrise. The above
      bodily based lexicalizations are thus linguistic manifestations of a broader
      macro-cultural worldview and its psycho-cognitive reality.

PMID- 22417144
TI  - Augmenter of liver regeneration attenuates tubular cell apoptosis in acute kidney
      injury in rats: the possible mechanisms.
AB  - Augmenter of liver regeneration (ALR), the expression of which increased in rat
      kidneys after renal ischemia/reperfusion (I/R) injury, enhances renal tubular
      cell regeneration in vivo and in vitro. We aimed to investigate the effects of
      ALR on apoptosis of renal tubular cells after renal I/R injury in vivo and
      consider the possible mechanisms. Rats that were subjected to bilateral renal
      ischemia for 60 min followed by reperfusion were administered with either vehicle
      or recombinant human ALR (rhALR). Renal dysfunction and histologic injury were
      assessed by the measurement of serum biochemical markers and histological
      grading. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated
      dUTP-biotin nick-end labeling (TUNEL). Caspase-3 activity was measured using a
      colorimetric protease assay. Expression of Bcl-2, Bax Fas, phosphorylated-Akt (p
      Akt), and phosphorylated-p53 (p-p53) was determined by western blotting. Compared
      with vehicle-treated rats, renal dysfunction and histologic injury were
      significantly attenuated by administration of rhALR. The number of TUNEL-positive
      tubular cells and caspase-3 activity were decreased, Bcl-2 and p-Akt expression
      was up-regulated, and Bax and p-p53 expression was down-regulated by
      administration of rhALR. However, administration of rhALR had no effect on Fas
      protein expression. These results indicate that the protective effect of rhALR on
      renal I/R injury is associated with its anti-apoptotic action in renal tubular
      cells. RhALR inhibits apoptosis by increasing the ratio of Bcl-2 to Bax and by
      decreasing the activity of caspase-3. The activation of Akt and inactivation of
      p53 are involved in the rhALR anti-apoptosis process.

PMID- 22417146
TI  - Older Australians and hospital care.

PMID- 22417147
TI  - Falls in older people receiving in-home informal care across Victoria: influence
      on care recipients and caregivers.
AB  - AIM: Older people receiving informal care at home appear at high falls risk. This
      study investigates frequency, circumstances and factors associated with falls
      risk for older care recipients, and their informal caregivers. METHODS: Ninety
      six dyads, recruited from caregiver agencies, underwent a home assessment,
      including falls risk, function, depression, quality of life, self-rated health
      and carer burden. RESULTS: Care recipients were at high falls risk. In the past
      12 months, 58% had fallen and 26% twice or more. Common falls risk factors were
      polypharmacy, multiple medical conditions and requiring functional assistance.
      Caregivers exhibited multiple health problems, moderate burden and reduced
      quality of life. Where care recipients had high falls risk, caregivers had
      significantly higher carer burden and depression. Low functional level and high
      care recipient health problems were independently associated with risk of falling
      (P < 0.05). CONCLUSION: Strategies to reduce falls risk in this cohort are
      necessary, together with supporting the needs of the caregiver.

PMID- 22417148
TI  - Validity and reliability of the Geriatric Anxiety Inventory in Parkinson's
      disease.
AB  - AIM: To examine the psychometric properties of a novel anxiety rating scale, the
      Geriatric Anxiety Inventory (GAI) in Parkinson's disease (PD). METHOD: The
      predictive validity of the GAI was tested against the presence of any DSM-IV
      anxiety disorders in 58 PD patients using receiver operating curve analysis. The
      concurrent validity of this scale was also studied against the state half of the
      Spielberger State Trait Anxiety Inventory (STAI). The internal consistency and
      test-retest reliability of the GAI were also examined. RESULTS: The GAI displayed
      good concurrent validity against the STAI and the DSM-IV. It also showed good
      internal consistency and test-retest reliability. CONCLUSIONS: This study
      suggested that the GAI is an appropriate scale to use in non-demented PD
      patients.

PMID- 22417149
TI  - The application of ecological thinking to better understand the needs of
      communities of older people.
AB  - AIM: This research applied ecological thinking to develop a more integrated or
      ecological understanding of the needs and aspirations of communities of older
      people. METHODS: A three-stage methodology was utilised. Stage one entailed the
      thematic analysis of resident satisfaction surveys collected from 1000 residents
      of aged living and care facilities to identify issues impacting upon their lives.
      In stage two these findings were critiqued through a key stakeholder forum. In
      stage three findings were authenticated through resident interviews and
      workshops. RESULTS: The findings suggest that an ecological framework for the
      well-being of older people living in residential communities can be
      conceptualised as the four domains of the physical environment, social
      environment, governance and active living. CONCLUSIONS: This framework for the
      ecology of resident well-being developed through this research informs an
      ecological approach to service providers' planning to promote the health and well
      being of residents of communities of older people.

PMID- 22417150
TI  - Associations between perception of wellness and health-related quality of life,
      comorbidities, modifiable lifestyle factors and demographics in older
      Australians.
AB  - AIM: The associations between perceived wellness and health-related quality of
      life, comorbidities and modifiable lifestyle factors in older adults were
      explored. METHODS: Self-administered questionnaires including the Perceived
      Wellness Survey and the 36-Item Short Form of the Medical Outcomes Study version
      two were distributed to 328 community-living adults aged 65 years and over.
      RESULTS: Results showed positive associations between perception of wellness and
      health-related quality of life. General health (r(249) = 0.66, P < 0.01),
      vitality (r(249) = 0.59, P < 0.01) and mental health (r(249) = 0.52, P < 0.01)
      had the strongest association with perceived wellness; and social functioning
      (r(249) = 0.3, P < 0.01) and pain (r(249) = 0.36, P < 0.01) the lowest. Perceived
      wellness was influenced by hearing, mobility, memory, chronic disease, exercise,
      gambling and single status. CONCLUSION: The study identified that perceived
      wellness in older adults is a multidimensional construct.

PMID- 22417140
TI  - Hypothalamic inflammation: a double-edged sword to nutritional diseases.
AB  - The hypothalamus is one of the master regulators of various physiological
      processes, including energy balance and nutrient metabolism. These regulatory
      functions are mediated by discrete hypothalamic regions that integrate metabolic
      sensing with neuroendocrine and neural controls of systemic physiology. Neurons
      and nonneuronal cells in these hypothalamic regions act supportively to execute
      metabolic regulations. Under conditions of brain and hypothalamic inflammation,
      which may result from overnutrition-induced intracellular stresses or disease
      associated systemic inflammatory factors, extracellular and intracellular
      environments of hypothalamic cells are disrupted, leading to central metabolic
      dysregulations and various diseases. Recent research has begun to elucidate the
      effects of hypothalamic inflammation in causing diverse components of metabolic
      syndrome leading to diabetes and cardiovascular disease. These new understandings
      have provocatively expanded previous knowledge on the cachectic roles of brain
      inflammatory response in diseases, such as infections and cancers. This review
      describes the molecular and cellular characteristics of hypothalamic inflammation
      in metabolic syndrome and related diseases as opposed to cachectic diseases, and
      also discusses concepts and potential applications of inhibiting
      central/hypothalamic inflammation to treat nutritional diseases.

PMID- 22417151
TI  - Course and prognostic factors of disability in community-dwelling older people
      with mild disability: the Rotterdam Study.
AB  - AIM: To study the prognosis of disability of community-dwelling older people with
      mild disability at baseline. METHODS: We used data from the Rotterdam Study: a
      community-based prospective cohort study of community-dwelling older people. We
      evaluated sociodemographic factors, lifestyle variables, health conditions and
      disability status at baseline and follow-up after 6 years. Disability was defined
      as a score on the Health Assessment Questionnaire. RESULTS: At baseline the
      population consisted of 1166 older people with mild disability with a mean age of
      69.7 (55-93) years. At follow-up 18% of the study population recovered from mild
      disability, 20% stayed mildly disabled, 31% became severely disabled, while 32%
      were deceased. At follow-up relatively more men died while more women had a
      worsened disability. Age and income were predictors of disability decrease.
      Alcohol use seemed to be significantly protective against death. CONCLUSION: Just
      a few prognostic factors appeared to be related to disability 6 years later.

PMID- 22417152
TI  - 'I'm older and more interested in my community': older people's contributions to
      social capital.
AB  - AIM: To explore and compare older people's contributions to social capital in a
      large rural community. METHODS: Data were collected from a large representative
      sample (n= 1431), through a social capital questionnaire. The survey was cross
      sectional and measured frequency of participation across different age cohorts in
      informal social activities, group activities and community and civic activities.
      RESULTS: Age and life stage pattern proved to be a factor in determining the
      types of activities people were involved in. While younger people were more
      involved in social participation that involved public places or group and
      sporting events, older people, particularly those in the retirement age group of
      60-69 were more involved in community and civic activities. CONCLUSION: Older
      people living in non-metropolitan areas are not only recipients of social
      capital. Their considerable involvement in volunteer groups, service clubs,
      church groups and local government demonstrates significant involvement in civic
      and community life.

PMID- 22417153
TI  - Geriatric assessment and intervention in an emergency department observation unit
      reduced re-attendance and hospitalisation rates.
AB  - AIM: To determine the efficacy of geriatric assessment and intervention in an
      emergency department observation unit (EDOU). METHODS: This was a single-centre,
      before/after prospective study. The control group received the usual EDOU care.
      Intervention group received geriatric assessment and intervention before
      discharge. Patients were followed up at 3, 6, 9 and 12 months. End-points
      included falls and functional scores obtained via telephone, and unscheduled ED
      re-attendance and hospitalisation obtained through electronic records. RESULTS:
      The study population included 172 control and 315 intervention group patients. A
      total of 71.7% of patients in the intervention group had hidden needs that
      required intervention. The intervention group had significantly less ED re
      attendance (adjusted incidence rate ratio (IRR) 0.59, 95% confidence interval
      (CI) 0.48-0.71) and hospitalisation rates (adjusted IRR 0.64, 95% CI 0.51-0.79)
      at 12 months. CONCLUSION: Older patients admitted to an EDOU are an at-risk group
      and benefit from geriatric assessment before discharge.

PMID- 22417154
TI  - An update on the pilot trial of consumer-directed care for older persons in
      Australia.
AB  - The Australian Government has commenced a two-year pilot of consumer-directed
      care (CDC) across 500 home and community aged care packages. This policy paper
      discusses the model being trialled in Australia in light of the UK's Individual
      Budgets' Pilot Programme and the USA's Cash and Counselling Demonstration. The
      results of these randomised controlled studies suggest that older people vary in
      their preferences for consumer direction and that many find the administrative
      tasks of implementing CDC programs difficult. The relatively restricted model of
      CDC that the Australian Government is trialling may minimise the problems
      encountered in the overseas programs, but does not allow consumers to hire family
      or friends which they preferred to do overseas.

PMID- 22417155
TI  - Quality of life for older people in residential care is related to connectedness,
      willingness to enter care, and co-residents.
AB  - AIM: To establish associations with quality of life (QOL) of older people in long
      term residential care facilities in two New Zealand cities. METHODS: The outcome
      measure of QOL was the Life Satisfaction Index. We used multiple linear
      regression to explore how broad categories of factors might contribute to QOL.
      RESULTS: A total of 599 people (median age of 85 years; 74% women) participated.
      Response rates were 85% for facilities and 83% for residents. A resident's QOL
      was significantly related to the QOL of co-residents. QOL was higher for people
      who were more positive about entry to residential care, more physically able, and
      not depressed, and for those with more family and emotional support. CONCLUSION:
      Attending to the circumstances around entry to residential care may enhance QOL,
      as may promoting physical activity, treating depression and ensuring older people
      remain emotionally connected to their families. In choosing a facility, noting
      the QOL of co-residents is important.

PMID- 22417156
TI  - Which Aged Care inpatients are potentially suitable for community-based acute
      care?
AB  - AIM: To identify Aged Care inpatients potentially suitable for Acute/Post-Acute
      Care (APAC)-Aged Care, a new service offering community-based acute care as an
      alternative to hospital admission for frail older people. METHODS: Criteria were
      developed to identify suitable patients for APAC-Aged Care and applied to
      consecutive Aged Care inpatient admissions at Royal North Shore Hospital, Sydney,
      Australia, through retrospective chart review. RESULTS: Only 5/90 reviewed
      patients were potentially suitable for APAC-Aged Care. All five were from
      Residential Aged Care Facilities. The median age of the 90 patients was 86 years;
      30% lived in Residential Aged Care Facilities; 53% of patients were medically
      stable on presentation; 70% required investigations beyond a standard baseline
      set; 27% had either no new functional decline on presentation or adequate
      community support to manage this; 91% had allied health input and 41% had
      medical/surgical consultation. CONCLUSION: APAC-Aged Care is a potentially
      suitable alternative to acute inpatient hospitalisation in a select minority of
      Aged Care patients.

PMID- 22417157
TI  - Ways in which 'community' benefits frail older women's well-being: 'we are much
      happier when we feel we belong'.
AB  - AIM: This paper aims to explore frail older women's lived experiences of
      'community' and which aspects of 'community' they perceive as beneficial to their
      well-being. METHOD: This qualitative project used a mixed methodological approach
      which integrated aspects of descriptive phenomenology and grounded theory. Ten
      frail, older women residing in South East Melbourne, Australia participated in in
      depth interviews. RESULTS: This research obtained a rich and detailed account of
      the aspects of 'community' identified by participants as enhancing their well
      being. These included: social contact, community dynamics, feelings of support
      and positive orientation. CONCLUSION: This paper has increased our understanding
      of the factors supporting well-being of frail older women. Service providers
      should actively consider how they can strengthen these factors to improve social
      connectedness for frail older women by the use of volunteers, developing social
      networks and increasing availability and quality of community-based activities.

PMID- 22417158
TI  - The gastro-esophageal reflux barrier: biophysical analysis on 3D models of
      anatomy from magnetic resonance imaging.
AB  - BACKGROUND: The function and structure of the gastro-esophageal junction (GEJ)
      determine its efficacy as a reflux barrier. This study presents a novel
      methodology for the quantitative assessment of GEJ and proximal gastric
      morphology from magnetic resonance (MR) imaging. Based on this data we propose a
      new conceptualization of the hypothesis that a flap valve mechanism contributes
      to reflux protection. METHODS: 3D models of the GEJ and proximal stomach were
      reconstructed from MR images in 12 healthy volunteers during respiration and on
      eating a test meal to maximum satiation. A rotating plane analysis measured the
      gastro-esophageal insertion angle and span of contact. An ellipsoid fit provided
      quantitative assessment of gastric shape and orientation relative to a fixed
      anatomical reference point. Position of the esophageal insertion on the 'gastric
      ellipse' was noted. An ellipsoid-cylinder model was designed to analyze the
      relationships among parameters describing the GEJ morphology. KEY RESULTS: The
      insertion angle became more acute on expiration, but did not change with meal
      ingestion. In contrast the span of contact did not vary with respiration, but
      increased with gastric filling. Changes in gastric morphology with distension
      further augmented the span of gastro-esophageal contact in almost 70% of the
      studies. CONCLUSIONS & INFERENCES: Novel MR imaging and biophysical analysis of
      the GEJ and proximal stomach provide a quantitative description of structures
      contributing to the reflux barrier. Changes in these parameters during
      respiration and on eating support the hypothesis that structural components of a
      functional 'flap valve' like mechanism contribute to reflux protection.

PMID- 22417159
TI  - DNA sequence variation and regulation of genes involved in pathogenesis of
      pulmonary tuberculosis.
AB  - DNA sequence variations [copy number variations, single nucleotide polymorphisms
      (SNPs) and microsatellite repeats] play an important role in
      susceptibility/resistance to tuberculosis and other infectious diseases like
      malaria and HIV. Different population exhibit variable associations with
      tuberculosis susceptibility and severity because of DNA sequence variations in
      both host and parasite. A number of genes and their polymorphisms have been
      identified that appear to be important in tuberculosis. In this article, several
      case-control studies of tuberculosis including a number of genes in different
      population have been explored. Furthermore, this review summarizes the current
      studies of host polymorphisms and their association with tuberculosis in
      different population. We have computationally predicted 275 SNPs which occur in
      transcription factor binding sites for transcription factors in 19 genes involved
      in pathogenesis of tuberculosis. Some common SNPs are rs1327474, rs755622,
      rs1801274, rs396991, rs5030737, rs1800451, rs1800450, rs3763313 rs3763313,
      rs9268494 and rs9268492 that have been found to play a role in disease. Presence
      of non-synonimous polymorphisms in coding region might affect the structure of
      protein, whereas polymorphisms in promoter region affect the level of gene
      products, consequently altering the susceptibility/resistance to disease. Based
      on this prediction, we hypothesize that these genes play an important role in
      susceptibility to tuberculosis through an altered expression of gene product via
      the modification of transcriptional regulation of gene.

PMID- 22417160
TI  - Graphene-based chemiluminescence resonance energy transfer for homogeneous
      immunoassay.
AB  - We report on chemiluminescence resonance energy transfer (CRET) between graphene
      nanosheets and chemiluminescent donors. In contrast to fluorescence resonance
      energy transfer, CRET occurs via nonradiative dipole-dipole transfer of energy
      from a chemiluminescent donor to a suitable acceptor molecule without an external
      excitation source. We designed a graphene-based CRET platform for homogeneous
      immunoassay of C-reactive protein (CRP), a key marker for human inflammation and
      cardiovascular diseases, using a luminol/hydrogen peroxide chemiluminescence (CL)
      reaction catalyzed by horseradish peroxidase. According to our results, anti-CRP
      antibody conjugated to graphene nanosheets enabled the capture of CRP at the
      concentration above 1.6 ng mL(-1). In the CRET platform, graphene played a key
      role as an energy acceptor, which was more efficient than graphene oxide, while
      luminol served as a donor to graphene, triggering the CRET phenomenon between
      luminol and graphene. The graphene-based CRET platform was successfully applied
      to the detection of CRP in human serum samples in the range observed during acute
      inflammatory stress.

PMID- 22417161
TI  - Graphene at high bias: cracking, layer by layer sublimation, and fusing.
AB  - Graphene and few-layer graphene at high bias expose a wealth of phenomena due to
      the high temperatures reached. With in situ transmission electron microscopy, we
      observe directly how the current modifies the structure, and vice versa. In some
      samples, cracks propagate from the edges of the flakes, leading to the formation
      of narrow constrictions or to nanometer spaced gaps after breakdown. In other
      samples, we find layer-by-layer evaporation of few-layer graphene, which could be
      exploited for the controlled production of single layer graphene from
      multilayered samples. Surprisingly, we even find that two pieces of graphene that
      overlap can heal out at high bias and form one continuous sheet. These findings
      open up new avenues to structure graphene for specific device applications.

PMID- 22417163
TI  - Perceived poor sleep quality in the absence of polysomnographic sleep disturbance
      in women with severe premenstrual syndrome.
AB  - Women with severe premenstrual syndrome report sleep-related complaints in the
      late-luteal phase, but few studies have characterized sleep disturbances
      prospectively. This study evaluated sleep quality subjectively and objectively
      using polysomnographic and quantitative electroencephalographic measures in women
      with severe premenstrual syndrome. Eighteen women with severe premenstrual
      syndrome (30.5 +/- 7.6 years) and 18 women with minimal symptoms (controls, 29.2
      +/- 7.3 years) had polysomnographic recordings on one night in each of the
      follicular and late-luteal phases of the menstrual cycle. Women with premenstrual
      syndrome reported poorer subjective sleep quality when symptomatic in the late
      luteal phase compared with the follicular phase (P < 0.05). However, there were
      no corresponding changes in objective sleep quality. Women with premenstrual
      syndrome had more slow-wave sleep and slow-wave activity than controls at both
      menstrual phases (P < 0.05). They also had higher trait-anxiety, depression,
      fatigue and perceived stress levels than controls at both phases (P < 0.05) and
      mood worsened in the late-luteal phase. Both groups showed similar menstrual
      phase effects on sleep, with increased spindle frequency activity and shorter
      rapid eye movement sleep episodes in the late-luteal phase. In women with
      premenstrual syndrome, a poorer subjective sleep quality correlated with higher
      anxiety (r = -0.64, P = 0.005) and more perceived nighttime awakenings (r = 
      0.50, P = 0.03). Our findings show that women with premenstrual syndrome perceive
      their sleep quality to be poorer in the absence of polysomnographically defined
      poor sleep. Anxiety has a strong impact on sleep quality ratings, suggesting that
      better control of mood symptoms in women with severe premenstrual syndrome may
      lead to better subjective sleep quality.

PMID- 22417164
TI  - The role of carbonic anhydrase IX in hypoxia control in OSCC.
AB  - Tumoral microenvironments play a key role in the evolution of solid tumors. Tumor
      hypoxia is actively involved in the promotion of genetic instability, the
      invasive capacity of tumor cells, metastasis, and a worsening of the clinical
      evolution. Endogenous hypoxia markers are controlled by hypoxia-related genes,
      formed by HIF-1, which is related to several target genes that involve the energy
      metabolism, angiogenesis, and transmembrane carbonic anhydrases (CAs), mainly CA
      IX that is one of the tumor-related carbonic anhydrases. The goal of this paper
      is to establish the role of CA-IX as a hypoxia marker in OSCC, while analyzing
      its expression in this type of tumors and its relationship with several clinical
      and pathological parameters and prognosis, evaluating its relationship with
      angiogenesis, other hypoxia markers, and clarifying its role in chemotherapy and
      radiotherapy resistance.

PMID- 22417162
TI  - The sustainability of new programs and innovations: a review of the empirical
      literature and recommendations for future research.
AB  - BACKGROUND: The introduction of evidence-based programs and practices into
      healthcare settings has been the subject of an increasing amount of research in
      recent years. While a number of studies have examined initial implementation
      efforts, less research has been conducted to determine what happens beyond that
      point. There is increasing recognition that the extent to which new programs are
      sustained is influenced by many different factors and that more needs to be known
      about just what these factors are and how they interact. To understand the
      current state of the research literature on sustainability, our team took stock
      of what is currently known in this area and identified areas in which further
      research would be particularly helpful. This paper reviews the methods that have
      been used, the types of outcomes that have been measured and reported, findings
      from studies that reported long-term implementation outcomes, and factors that
      have been identified as potential influences on the sustained use of new
      practices, programs, or interventions. We conclude with recommendations and
      considerations for future research. METHODS: Two coders identified 125 studies on
      sustainability that met eligibility criteria. An initial coding scheme was
      developed based on constructs identified in previous literature on
      implementation. Additional codes were generated deductively. Related constructs
      among factors were identified by consensus and collapsed under the general
      categories. Studies that described the extent to which programs or innovations
      were sustained were also categorized and summarized. RESULTS: Although
      "sustainability" was the term most commonly used in the literature to refer to
      what happened after initial implementation, not all the studies that were
      reviewed actually presented working definitions of the term. Most study designs
      were retrospective and naturalistic. Approximately half of the studies relied on
      self-reports to assess sustainability or elements that influence sustainability.
      Approximately half employed quantitative methodologies, and the remainder
      employed qualitative or mixed methodologies. Few studies that investigated
      sustainability outcomes employed rigorous methods of evaluation (e.g., objective
      evaluation, judgement of implementation quality or fidelity). Among those that
      did, a small number reported full sustainment or high fidelity. Very little
      research has examined the extent, nature, or impact of adaptations to the
      interventions or programs once implemented. Influences on sustainability included
      organizational context, capacity, processes, and factors related to the new
      program or practice themselves. CONCLUSIONS: Clearer definitions and research
      that is guided by the conceptual literature on sustainability are critical to the
      development of the research in the area. Further efforts to characterize the
      phenomenon and the factors that influence it will enhance the quality of future
      research. Careful consideration must also be given to interactions among
      influences at multiple levels, as well as issues such as fidelity, modification,
      and changes in implementation over time. While prospective and experimental
      designs are needed, there is also an important role for qualitative research in
      efforts to understand the phenomenon, refine hypotheses, and develop strategies
      to promote sustainment.

PMID- 22417165
TI  - Micropatterning of metallopolymers: syntheses of back-to-back coupled octylated
      2,6-bis(pyrazolyl)pyridine ligands and their solution-processable coordination
      polymers.
AB  - This paper presents a 10-step synthetic route for the preparation of a series of
      new back-to-back coupled 2,6-bis(pyrazol-1-yl)pyridine (bpp) ligands (L0-L3)
      decorated with tetraoctyl chains. Ligand L1 self-assembles with Zn(2+) ion to
      form a highly soluble metallo-supramolecular polymer 1 with M(n) ~ 9600 g/mol. To
      demonstrate the processability of polymer 1, by following a "top-down" approach
      periodic one-dimensional fluorescent microstripes were fabricated on a silica
      substrate.

PMID- 22417167
TI  - Identification of proteasome components required for apical localization of
      Chaoptin using functional genomics.
AB  - Abstract: the distinct localization of membrane proteins with regard to cell
      polarity is crucial for the structure and function of various organs in
      multicellular organisms. However, the molecules and mechanisms that regulate
      protein localization to particular subcellular domains are still largely unknown.
      To identify the genes involved in regulation of protein localization, the authors
      performed a large-scale screen using a Drosophila RNA interference (RNAi)
      library, by which Drosophila genes could be knocked down in a tissue- and stage
      specific manner. Drosophila photoreceptor cells have a morphologically distinct
      apicobasal polarity, along which Chaoptin (Chp), a glycosylphosphatidylinositol
      (GPI)-anchored membrane protein, and the Na (+) , K(+) -ATPase are localized to
      the apical and basolateral domains, respectively. By examining the subcellular
      localization of these proteins, the authors identified 106 genes whose knockdown
      resulted in mislocalization of Chp and Na(+) , K(+) -ATPase. Gene ontology
      analysis revealed that the knockdown of proteasome components resulted in
      mislocalization of Chp to the basolateral plasma membrane. These results suggest
      that the proteasome is involved, directly or indirectly, in selective
      localization of Chp to the apical plasma membrane of Drosophila photoreceptor
      cells.

PMID- 22417166
TI  - Identification of single nucleotide polymorphisms in the bovine Toll-like
      receptor 1 gene and association with health traits in cattle.
AB  - Bovine mastitis remains the most common and costly disease of dairy cattle
      worldwide. A complementary control measure to herd hygiene and vaccine
      development would be to selectively breed cattle with greater resistance to
      mammary infection. Toll-like receptor 1 (TLR1) has an integral role for the
      initiation and regulation of the immune response to microbial pathogens, and has
      been linked to numerous inflammatory diseases. The objective of this study was to
      investigate whether single nucleotide polymorphisms (SNPs) within the bovine TLR1
      gene (boTLR1) are associated with clinical mastitis (CM).Selected boTLR1 SNPs
      were analysed within a Holstein Friesian herd. Significant associations were
      found for the tagging SNP -79 T > G and the 3'UTR SNP +2463 C > T. We observed
      favourable linkage of reduced CM with increased milk fat and protein, indicating
      selection for these markers would not be detrimental to milk quality.
      Furthermore, we present evidence that some of these boTLR1 SNPs underpin
      functional variation in bovine TLR1. Animals with the GG genotype (from the tag
      SNP -79 T > G) had significantly lower boTLR1 expression in milk somatic cells
      when compared with TT or TG animals. In addition, stimulation of leucocytes from
      GG animals with the TLR1-ligand Pam3csk4 resulted in significantly lower levels
      of CXCL8 mRNA and protein.SNPs in boTLR1 were significantly associated with CM.
      In addition we have identified a bovine population with impaired boTLR1
      expression and function. This may have additional implications for animal health
      and warrants further investigation to determine the suitability of identified
      SNPs as markers for disease susceptibility.

PMID- 22417168
TI  - Endogenous neural precursors influence grafted neural stem cells and contribute
      to neuroprotection in the parkinsonian rat.
AB  - Neuroprotective and neurorescue effects after neural stem/precursor cell (NPC)
      transplantation have been reported, but the mechanisms underlying such phenomena
      are not well understood. Our recent findings in a rat Parkinson's disease (PD)
      model indicate that transplantation of NPCs before a 6-hydroxydopamine (6-OHDA)
      insult can result in nigrostriatal protection which is associated with endogenous
      NPC proliferation, migration and neurogenesis. Here, we sought to determine
      whether the observed endogenous NPC response (i) contributes to transplanted NPC
      mediated neuroprotection; and/or (ii) affects graft phenotype and function. Host
      Fischer 344 rats were administered the antimitotic agent cytosine-beta-d
      arabinofuranoside (Ara-C) to eliminate actively proliferating endogenous neural
      precursors before being transplanted with NPCs and treated with 6-OHDA to induce
      nigrostriatal degeneration. Behavioral and histological analyses demonstrate that
      the neuroprotective response observed in NPC transplanted animals which had not
      received Ara-C was significantly attenuated in animals which did receive pre
      transplant Ara-C. Also, while grafts in Ara-C-treated animals showed no decrease
      in cell number, they exhibited significantly reduced expression of the neural
      stem cell regulators nestin and sonic hedgehog. In addition, inhibition of the
      endogenous NPC response resulted in an exaggerated host glial reaction. Overall,
      the study establishes for the first time that endogenous NPCs contribute to
      transplanted NPC-mediated therapeutic effects by affecting both grafted and
      mature host cells in unique ways. Thus, both endogenous and transplanted NPCs are
      important in creating an environment suitable for neural protection and rescue,
      and harnessing their synergistic interaction may lead to the optimization of cell
      based therapies for PD.

PMID- 22417170
TI  - Onychomadesis following hand, foot, and mouth disease: a case report from Italy
      and review of the literature.

PMID- 22417169
TI  - Racial/ethnic disparities in health and health care among U.S. adolescents.
AB  - OBJECTIVE: To examine racial/ethnic disparities in medical and oral health
      status, access to care, and use of services in U.S. adolescents. DATA SOURCE:
      Secondary data analysis of the 2003 National Survey of Children's Health. The
      survey focus was children 0-17 years old. STUDY DESIGN: Bivariate and
      multivariable analyses were conducted for white, African American, Latino,
      Asian/Pacific Islander, American Indian/Alaskan Native, and multiracial
      adolescents 10-17 years old (n = 48,742) to identify disparities in 40 measures
      of health and health care. PRINCIPAL FINDINGS: Certain disparities were
      especially marked for specific racial/ethnic groups and multiracial youth. These
      disparities included suboptimal health status and lack of a personal doctor or
      nurse for Latinos; suboptimal oral health and not receiving all needed
      medications in the past year for African Americans; no physician visit or mental
      health care in the past year for Asian/Pacific Islanders; overweight/obesity,
      uninsurance, problems getting specialty care, and no routine preventive visit in
      the past year for American Indian/Alaska Natives; and not receiving all needed
      dental care in multiracial youth. CONCLUSIONS: U.S. adolescents experience many
      racial/ethnic disparities in health and health care. These findings indicate a
      need for ongoing identification and monitoring of and interventions for
      disparities for all five major racial/ethnic groups and multiracial adolescents.

PMID- 22417171
TI  - Innovative moments and change in client-centered therapy.
AB  - Previous studies have used the Innovative Moments Coding System (IMCS) to
      describe the process of change in Narrative Therapy (NT) and in Emotion-Focused
      Therapy (EFT). This study aims to extend this research program to a sample of
      Client-Centered Therapy (CCT). The IMCS was applied to six cases of CCT for
      depression to track the Innovative Moments (IMs) which are exceptions to the
      problematic self-narrative in therapeutic conversation. Results suggest that IMCS
      can be applied to CCT, allowing the tracking of IMs' emergence. The analysis
      based on a generalized linear model revealed that the overall amount of IMs is
      significantly associated with symptom improvement, which is congruent with former
      studies done with the IMCS.

PMID- 22417172
TI  - Intrahepatic cholangiocarcinomas in cirrhosis are hypervascular in comparison
      with those in normal livers.
AB  - BACKGROUND AND AIMS: Intrahepatic cholangiocarcinomas (ICCs) are usually
      adenocarcinomas with fibrotic and hypovascular stroma. Intrahepatic
      cholangiocarcinomas in cirrhosis and precirrhotic liver (ICC-cirrhosis) are
      increasingly being diagnosed, and can display hypervascular enhancement
      resembling a hepatocellular carcinoma on dynamic imaging. METHODS: In this study
      using ICC-cirrhosis (71 cases), ICC with non-specific reactive changes (ICC
      reactive) (72 cases) and the cholangiocarcinoma component of combined
      hepatocellular cholangiocarcinoma (HCC-ICC) (30 cases), we tried to compare the
      tumour vasculature. RESULTS: It was found that ICC-cirrhosis and the
      cholangiocarcinoma component of HCC-ICC showed a higher density of arteries and
      microvessels (1.59 +/- 0.58/mm(2) (mean +/- SD) and 140 +/- 43/mm(2) in ICC
      cirrhosis and 1.74 +/- 0.67/mm(2) and 131 +/- 46/mm(2) in the cholangiocarcinoma
      component of HCC-ICC) than in ICC-reactive (1.26 +/- 0.61/mm(2) and 103 +/-
      45/mm(2) ). Dynamic computed tomography (CT) and magnetic resonance imaging (MRI)
      showed that a majority of ICC-cirrhosis displayed strong hypervascular
      enhancement, whereas one-third of ICC-reactive each showed strong, weak and no or
      minimal enhancement respectively. The increased vascular density was positively
      correlated with enhanced arterial phase of dynamic CT and MRI. CONCLUSION: The
      density of arteries and microvessels of ICC-cirrhosis was higher than that in ICC
      reactive and comparable to that in the cholangiocarcinoma component of HCC-ICC,
      and the higher density of arteries and microvessels in ICC may be responsible for
      the hypervascular enhancement of ICC-cirrhosis.

PMID- 22417173
TI  - Systems pharmacology of complex diseases.
AB  - Systems pharmacology approaches can be used to identify and predict drug-induced
      adverse events. Disease-centered networks within the human interactome allow us
      to predict which drugs may produce a similar pathophysiology. Such predictions
      can be tested in animal models.

PMID- 22417174
TI  - All-trans retinal mediates light-induced oxidation in single living rod
      photoreceptors.
AB  - All-trans retinal is a potent photosensitizer that is released in photoreceptor
      outer segments by the photoactivated visual pigment following the detection of
      light. Photoreceptor outer segments also contain high concentrations of
      polyunsaturated fatty acids, and are thus particularly susceptible to oxidative
      damage such as that initiated by light via a photosensitizer. Upon its release,
      all-trans retinal is reduced within the outer segment to all-trans retinol,
      through a reaction requiring metabolic input in the form of NADPH. The phototoxic
      potential of physiologically generated all-trans retinal was examined in single
      living rod photoreceptors obtained from frog (Rana pipiens) retinas. Light
      induced oxidation was measured with fluorescence imaging using an oxidation
      sensitive indicator dye from the shift in fluorescence between the intact and
      oxidized forms. Light-induced oxidation was highest in metabolically compromised
      rod outer segments following photoactivation of the visual pigment rhodopsin, and
      after a time interval, sufficiently long to ensure the release of all-trans
      retinal. Furthermore, light-induced oxidation increased with the concentration of
      exogenously added all-trans retinal. The results show that the all-trans retinal
      generated during the detection of light can mediate light-induced oxidation. Its
      removal through reduction to all-trans retinol protects photoreceptor outer
      segments against light-induced oxidative damage.

PMID- 22417175
TI  - Renal mass: a confusing feature of sarcoidosis.
AB  - Sarcoidosis is a systemic disorder with a wide spectrum of clinical involvements.
      Renal mass is a very rare condition in sarcoidosis. Here, we report a 34-year-old
      female with renal masses and advanced renal failure. The condition created a lot
      of diagnosis difficulties. Finally, after histologic diagnosis and corticosteroid
      therapy, renal masses were resolved and she became free from dialysis.

PMID- 22417176
TI  - Immediate effects of acupuncture on biceps brachii muscle function in healthy and
      post-stroke subjects.
AB  - BACKGROUND: The effects of acupuncture on muscle function in healthy subjects are
      contradictory and cannot be extrapolated to post-stroke patients. This study
      evaluated the immediate effects of manual acupuncture on myoelectric activity and
      isometric force in healthy and post-stroke patients. METHODS: A randomized
      clinical trial, with parallel groups, single-blinded study design, was conducted
      with 32 healthy subjects and 15 post-stroke patients with chronic hemiparesis.
      Surface electromyography from biceps brachii during maximal isometric voluntary
      tests was performed before and after 20-min intermittent, and manual stimulation
      of acupoints Quchi (LI11) or Tianquan (PC2). Pattern differentiation was
      performed by an automated method based on logistic regression equations. RESULTS:
      Healthy subjects showed a decrease in the root mean-squared (RMS) values after
      the stimulation of LI11 (pre: 1.392 +/- 0.826 V; post: 0.612 +/- 0.0.320 V; P =
      0.002) and PC2 (pre: 1.494 +/- 0.826 V; post: 0.623 +/- 0.320 V; P = 0.001).
      Elbow flexion maximal isometric voluntary contraction (MIVC) was not
      significantly different after acupuncture stimulation of LI11 (pre: 22.2 +/- 10.7
      kg; post: 21.7 +/- 9.5 kg; P = 0.288) or PC2 (pre: 18.8 +/- 4.6 kg; post: 18.7 +/
      6.0 kg; P = 0.468). Post-stroke patients did not exhibit any significant
      decrease in the RMS values after the stimulation of LI11 (pre: 0.627 +/- 0.335 V;
      post: 0.530 +/- 0.272 V; P = 0.187) and PC2 (pre: 0.601 +/- 0.258 V; post: 0.591
      +/- 0.326 V; P = 0.398). Also, no significant decrease in the MIVC value was
      observed after the stimulation of LI11 (pre: 9.6 +/- 3.9 kg; post: 9.6 +/- 4.7
      kg; P = 0.499) or PC2 (pre: 10.7 +/- 5.6 kg; post: 10.2 +/- 5.3 kg; P = 0.251).
      Different frequency of patterns was observed among healthy subjects and post
      stroke patients groups (chi2 = 9.759; P = 0.021). CONCLUSION: Manual acupuncture
      provides sufficient neuromuscular stimuli to promote immediate changes in motor
      unit gross recruitment without repercussion in maximal force output in healthy
      subjects. Post-stroke patients did not exhibit significant reduction on the
      myoelectric activity and maximal force output after manual acupuncture and needs
      further evaluation with a larger sample. TRIAL REGISTRATION: Brazilian Clinical
      Trials Registry RBR-5g7xqh.

PMID- 22417177
TI  - Diabetes diagnosis and autopsy.

PMID- 22417179
TI  - Edge structural stability and kinetics of graphene chemical vapor deposition
      growth.
AB  - The energetics and growth kinetics of graphene edges during CVD growth on Cu(111)
      and other catalyst surfaces are explored by density functional theory (DFT)
      calculations. Different from graphene edges in vacuum, the reconstructions of
      both armchair (AC) and zigzag (ZZ) edges are energetically less stable because of
      the passivation of the edges by the catalytic surface. Furthermore, we predicated
      that, on the most used Cu(111) catalytic surface, each AC-like site on the edge
      is intended to be passivated by a Cu atom. Such an unexpected passivation
      significantly lowers the barrier of incorporating carbon atoms onto the graphene
      edge from 2.5 to 0.8 eV and therefore results in a very fast growth of the AC
      edge. These theoretical results are successfully applied to explain the broad
      experimental observations that the ZZ egde is the dominating edge type of growing
      graphene islands on a Cu surface.

PMID- 22417180
TI  - It's time to fill the glass!

PMID- 22417181
TI  - The challenge of follow-up visits after cataract surgery in the developing world.

PMID- 22417183
TI  - Quantum Hall effect in graphene with superconducting electrodes.
AB  - We have realized an integer quantum Hall system with superconducting contacts by
      connecting graphene to niobium electrodes. Below their upper critical field of 4
      T, an integer quantum Hall effect coexists with superconductivity in the leads
      but with a plateau conductance that is larger than in the normal state. We
      ascribe this enhanced quantum Hall plateau conductance to Andreev processes at
      the graphene-superconductor interface leading to the formation of so-called
      Andreev edge-states. The enhancement depends strongly on the filling-factor and
      is less pronounced on the first plateau due to the special nature of the zero
      energy Landau level in monolayer graphene.

PMID- 22417184
TI  - A framework for costing diagnostic methods in oral health care: an application
      comparing a new imaging technology with the conventional approach for maxillary
      canines with eruption disturbances.
AB  - OBJECTIVES: The aims were (i) to propose a framework for costing diagnostic
      methods in oral health care and (ii) to illustrate the application of the
      framework to the radiographic examination of maxillary canines with eruption
      disturbances. METHODS: The framework for costing, following Drummond et al.
      (2005), includes three elements: (i) identification of different resources used
      in producing and delivering the service, (ii) measurement of the amount of each
      resource required and (iii) valuation of the resources in monetary terms. Four
      data collection instruments were designed - a protocol for apportioning the cost
      of capital equipment to each diagnostic procedure, separate forms for recording
      consumable items, for the time of different health care providers used for a
      diagnostic examination and a patient survey for calculation of the total cost to
      the patient associated with the examination. The framework was applied to the
      radiographic examination of maxillary canines with eruption disturbances
      comparing two imaging methods: (i) a new method with cone beam computed
      tomography and panoramic radiography and (ii) a conventional method using
      intraoral and panoramic radiography. The primary analysis was performed from the
      perspective of the health care system. A separate analysis included patient costs
      with health care system costs to provide a societal perspective. Comparison of
      the two perspectives allows consideration of whether any costs savings to the
      health care system are generated at the expense of greater costs for patients and
      their families. Data for the cost-analysis were retrieved from 47 patients (mean
      age 14 years) referred to a department of radiology for examination of maxillary
      canines. RESULTS: Application of the framework for costing allowed us to compare
      the resources used to perform examinations of the two methods. The mean total
      cost per examination for the new method was 128.38? and 81.80? for the
      conventional method, resulting in an incremental cost per examination of the new
      method of 46.58?. CONCLUSIONS: The application of the framework demonstrates the
      feasibility of measuring and comparing the total costs as well as the
      distribution of total costs between providers and patients for different
      approaches to this common examination.

PMID- 22417186
TI  - Attention mechanisms in children with anxiety disorders and in children with
      attention deficit hyperactivity disorder: implications for research and practice.
AB  - Inattention is among the most commonly referred problems for school-aged youth.
      Research suggests distinct mechanisms may contribute to attention problems in
      youth with anxiety disorders versus youth with attention deficit hyperactivity
      disorder (ADHD). This study compared children (8-17 years) with anxiety disorders
      (n = 24) and children (8-16 years) with ADHD (n = 23) on neurocognitive tests of
      both general and emotion-based attention processes. As hypothesized, children
      with ADHD demonstrated poorer selective and sustained attention, whereas youth
      with anxiety disorders demonstrated greater attentional bias toward threatening
      faces on a visual probe task. Findings suggest the neuropsychological
      differentiation of attention problems in anxious and ADHD children, despite
      potentially similar phenotypes.

PMID- 22417185
TI  - Catalytic mechanism of 4-oxalocrotonate tautomerase: significances of protein
      protein interactions on proton transfer pathways.
AB  - 4-Oxalocrotonate tautomerase (4-OT), a member of tautomerase superfamily, is an
      essential enzyme in the degradative metabolism pathway occurring in the Krebs
      cycle. The proton transfer process catalyzed by 4-OT has been explored previously
      using both experimental and theoretical methods; however, the elaborate catalytic
      mechanism of 4-OT still remains unsettled. By combining classical molecular
      mechanics with quantum mechanics, our results demonstrate that the native
      hexametric 4-OT enzyme, including six protein monomers, must be employed to
      simulate the proton transfer process in 4-OT due to protein-protein steric and
      electrostatic interactions. As a consequence, only three out of the six active
      sites in the 4-OT hexamer are observed to be occupied by three 2-oxo-4
      hexenedioates (2o4hex), i.e., half-of-the-sites occupation. This agrees with
      experimental observations on negative cooperative effect between two adjacent
      substrates. Two sequential proton transfers occur: one proton from the C3
      position of 2o4hex is initially transferred to the nitrogen atom of the general
      base, Pro1. Subsequently, the same proton is shuttled back to the position C5 of
      2o4hex to complete the proton transfer process in 4-OT. During the catalytic
      reaction, conformational changes (i.e., 1-carboxyl group rotation) of 2o4hex may
      occur in the 4-OT dimer model but cannot proceed in the hexametric structure. We
      further explained that the docking process of 2o4hex can influence the specific
      reactant conformations and an alternative substrate (2-hydroxymuconate) may serve
      as reactant under a different reaction mechanism than 2o4hex.

PMID- 22417187
TI  - Exploring the association between cognitive functioning and anxiety in children
      with autism spectrum disorders: the role of social understanding and aggression.
AB  - This study examined relations between anxiety, aggression, social understanding,
      IQ, and diagnosis in a sample of 231 children (ages 2-9) diagnosed with Autism
      Spectrum Disorders (ASDs; Autistic Disorder, Asperger's Disorder, Pervasive
      Developmental Disorder Not Otherwise Specified) in a hospital setting. Children
      were administered tests of IQ, and parents completed measures of remaining
      variables. ASD diagnosis was associated with level of anxiety, and level of IQ
      explained this relation. IQ was significantly and positively associated with
      anxiety. Tests of a developmental model to explain the relation between IQ and
      anxiety showed that social understanding and aggression mediated the relation for
      toddlers. For preschool- and early elementary school-aged children, respectively,
      three-way interactions between IQ, social understanding, and aggression predicted
      anxiety, and graphs of the interactions suggest that the association between IQ
      and anxiety is increasingly driven by either aggression or social understanding
      over the course of childhood.

PMID- 22417188
TI  - Parent and peer links to trajectories of anxious withdrawal from grades 5 to 8.
AB  - Individual differences in trajectories of anxious withdrawal were examined from
      Grades 5 to 8 across the transition to middle school in a community sample (N =
      283), using General Growth Mixture Modeling. Three distinct pathways of anxious
      withdrawal were identified: low-stable (78%), high-decreasing (12%), and high
      increasing (10%). In Grade 6, relative to the low-stable class, greater peer
      exclusion and more free time spent with mother predicted membership in the high
      decreasing class; higher peer exclusion predicted membership in the high
      increasing class. Within the high-increasing class, the growth of anxious
      withdrawal was predicted by lower parental autonomy-granting, less free time with
      mother, both nurturing and restrictive parenting, and greater peer exclusion.
      Results highlight the role of both parent-child relationship and peer
      difficulties in increasing the adjustment risk among youth who are anxiously
      withdrawn prior to the middle-school transition.

PMID- 22417190
TI  - Childhood family instability and mental health problems during late adolescence:
      a test of two mediation models--the TRAILS study.
AB  - This study tested whether childhood family instability is associated with mental
      health problems during adolescence through continued family instability and/or
      through a preadolescent onset of mental health problems. This test use data from
      a prospective population cohort of 2,230 Dutch adolescents (M age = 11.09, SD =
      0.56 at the initial assessment). Childhood family instability was associated with
      both internalizing problems and externalizing problems during late adolescence.
      The association between childhood family instability and adolescent mental health
      problems largely disappeared when controlling for preadolescent onset of mental
      health problems but only slightly when controlling for continued family
      instability during adolescence. These patterns were comparable for both types of
      mental health problems but relatively stronger for internalizing problems. These
      results suggest that growing up in an unpredictable family environment has long
      lasting negative mental health effects, most of which are due to a preadolescent
      onset of mental health problems.

PMID- 22417189
TI  - Enhancing youth outcomes following parental divorce: a longitudinal study of the
      effects of the new beginnings program on educational and occupational goals.
AB  - This study examined whether the New Beginnings Program for divorced families led
      to improvements in youth's educational goals and job aspirations 6 years
      following participation and tested whether several parenting and youth variables
      mediated the program effects. Participants were 240 youth aged 9 to 12 years at
      the initial assessment, and data were part of a randomized, experimental trial of
      a parenting skills preventive intervention targeting children's postdivorce
      adjustment. The results revealed positive effects of the program on youth's
      educational goals and job aspirations 6 years after participation for those who
      were at high risk for developing later problems at program entry. Further,
      intervention-induced changes in mother-child relationship quality and youth
      externalizing problems, internalizing problems, self-esteem, and academic
      competence at the 6-year follow-up mediated the effects of the program on the
      educational expectations of high-risk youth. Intervention-induced changes in
      youth externalizing problems and academic competence at the 6-year follow-up
      mediated the effects of the program on the job aspirations of high-risk youth.

PMID- 22417191
TI  - Strengthening effective parenting practices over the long term: effects of a
      preventive intervention for parentally bereaved families.
AB  - This study tested the effect of the Family Bereavement Program (FBP), a
      preventive intervention for bereaved families, on effective parenting (e.g.,
      caregiver warmth, consistent discipline) 6 years after program completion.
      Families (n = 101; 69% female caregivers; 77% Caucasian, 11% Hispanic) with
      children between ages 8 and 16 who had experienced the death of one parent were
      randomized to the FBP (n = 54) or a literature control condition (n = 47).
      Multiple regression analyses conducted within a multilevel framework indicated
      that the FBP had a significant positive impact on a multirater, multimeasure
      assessment of parenting at 6-year follow-up, controlling for pretest levels of
      parenting and child mental health problems. Mediation analyses showed that short
      term program effects on parenting, including caregiver warmth and effective
      discipline, significantly mediated the impact of the FBP on effective parenting 6
      years later. These findings indicate that a relatively cost-effective brief
      intervention for families who experienced a major stressor resulted in sustained
      effects on caregiver warmth and consistent discipline 6 years following the
      program.

PMID- 22417192
TI  - Interparent childrearing disagreement, but not dissimilarity, predicts child
      problems after controlling for parenting effectiveness.
AB  - Parental differences regarding childrearing may be operationalized as actual
      dissimilarity in the parenting actions or goals of the parents, or as perceived
      conflict or disagreement related to these dissimilarities. This study tested
      whether these two types of parental differences are each associated with child
      problems, independent of the contributions of parenting effectiveness. A
      community sample of 160 couples with a firstborn child (ages 2-5 years)
      participated. Mothers and fathers independently completed measures of
      childrearing disagreement, parenting behaviors and goals, and child behavior.
      Interparent childrearing disagreement accounted for unique variance in child
      internalizing and externalizing problems, even after controlling for family
      income, marital satisfaction, and parenting effectiveness. Dissimilarity in
      mother and father parenting behaviors (but not goals) was associated with child
      problems at the bivariate level, but not after controlling for parenting
      effectiveness.

PMID- 22417193
TI  - Family relationships and parental monitoring during middle school as predictors
      of early adolescent problem behavior.
AB  - The middle school years are a period of increased risk for youths' engagement in
      antisocial behaviors, substance use, and affiliation with deviant peers (Dishion
      & Patterson,  2006 ). This study examined the specific role of parental
      monitoring and of family relationships (mother, father, and sibling) that are all
      critical to the deterrence of problem behavior in early adolescence. The study
      sample comprised 179 ethnically diverse 6th-grade (46% female) students who were
      followed through 8th grade. Results indicated that parental monitoring and father
      youth connectedness were associated with reductions in problem behavior over
      time, and conflict with siblings was linked with increases in problem behaviors.
      No associations were found for mother-youth connectedness. These findings did not
      differ for boys and for girls, or for families with resident or nonresident
      fathers.

PMID- 22417195
TI  - Cortisol predicts behavioral dysregulation and length of stay among children
      admitted for psychiatric inpatient treatment.
AB  - Individual differences in behavioral regulation system (BRS) and stress response
      system (SRS) functioning may reflect greater biological sensitivity to context.
      The current study tested whether children's cortisol, a measure of the SRS, was
      related to observed dysregulated behavior, an indicator of the BRS, in a sample
      of children admitted for acute psychiatric inpatient care. In addition, cortisol
      and dysregulated behavior were tested as unique predictors of length of
      hospitalization over and above demographic factors, prior treatment history, and
      caretaker-reported psychiatric symptoms. The latter variables were tested as
      potential moderators of the relations of BRS and SRS functioning to length of
      hospitalization. Plasma cortisol was collected on the morning following hospital
      admission for 544 children (ages 6-12; 73% boys; 61% ethnic minority).
      Dysregulated behavior was operationalized as the mean number of timeouts
      administered by staff for noncompliant behavior per day of hospitalization.
      Caretakers reported on youth internalizing and externalizing symptomatology.
      Higher cortisol was modestly associated with greater dysregulated behavior. In a
      model including both cortisol and dysregulated behavior, each predicted longer
      hospitalization. Cortisol was positively related to length of stay only for
      children previously hospitalized, and the relation of dysregulated behavior to
      length of stay was stronger for older children. Dysregulated behavior and
      cortisol are related but independent predictors of acute psychiatric
      hospitalization duration. Direct measures of the SRS can add to the clinical
      picture regarding hospitalization in ways that observed behavior and caretaker
      report alone cannot.

PMID- 22417194
TI  - Social connectedness and one-year trajectories among suicidal adolescents
      following psychiatric hospitalization.
AB  - This study examined the extent to which posthospitalization change in
      connectedness with family, peers, and nonfamily adults predicted suicide
      attempts, severity of suicidal ideation, and depressive symptoms across a 12
      month follow-up period among inpatient suicidal adolescents. Participants were
      338 inpatient suicidal adolescents, ages 13 to 17, who were assessed at 3, 6, and
      12 months posthospitalization. General liner models were fitted for depressive
      symptoms and suicidal ideation outcomes, and logistic regression was used for the
      dichotomous suicide attempt outcome. The moderating effects of gender and
      multiple attempt history were examined. Adolescents who reported greater
      improvements in peer connectedness were half as likely to attempt suicide during
      the 12-month period. Improved peer connectedness was also associated with less
      severe depressive symptoms for all adolescents and with less severe suicidal
      ideation for female individuals, but only at the 3-month assessment time point.
      Improved family connectedness was related to less severe depressive symptoms and
      suicidal ideation across the entire year; for suicidal ideation, this protective
      effect was limited to nonmultiple suicide attempters. Change in connectedness
      with nonfamily adults was not a significant predictor of any outcome when changes
      in family and peer connectedness were taken into account. These results pointing
      to improved posthospitalization connectedness being linked to improved outcomes
      following hospitalization have important treatment and prevention implications
      given inpatient suicidal adolescents' vulnerability to suicidal behavior.

PMID- 22417196
TI  - Persistence of problematic sexual behaviors in children.
AB  - The purpose of this study was to identify personal and family predictors and
      correlates of persistence of problematic sexual behaviors (PSB) in children.
      Participants were the families of 49 children (ages 4-11 years) referred by Child
      Protective Services in 4 administrative districts of Quebec. Caregivers completed
      interviews and questionnaires twice at a 1-year interval. Results showed that 43%
      of children persisted with PSB. When age was controlled, greater exposure to
      sexualized behaviors in the family proved both a correlate and a predictor of PSB
      persistence in children 12 months later. Externalizing problems and somatic
      complaints emerged as correlates of PSB as well. Maltreatment subtypes did not
      predict PSB persistence.

PMID- 22417197
TI  - Factor structure and validity of the therapy process observational coding system
      for child psychotherapy-alliance scale.
AB  - The aim of this study was to examine the factor structure and psychometric
      properties of an observer-rated youth alliance measure, the Therapy Process
      Observational Coding System for Child Psychotherapy-Alliance scale (TPOCS-A). The
      sample was 52 youth diagnosed with anxiety disorders (M age = 12.43, SD = 2.23,
      range = 8-15; 56% boys; 98% Caucasian) drawn from a randomized controlled trial.
      Participants received a manualized individual cognitive behavioral treatment, the
      FRIENDS for life program, in public community clinics in Norway. Diagnostic
      status, treatment motivation, and perceived treatment credibility were assessed
      at pretreatment. Using the TPOCS-A, independent observers rated child-therapist
      alliance from the third therapy session. Child- and therapist-reported alliance
      measures were collected from the same session. An exploratory factor analysis
      supported a one-factor solution, which is consistent with previous studies of
      self- and observer-rated youth alliance scales. Psychometric analyses supported
      the interrater reliability, internal consistency, and convergent/divergent
      validity of the TPOCS-A. Accumulating psychometric evidence indicate that the
      TPOCS-A has the potential to fill a measurement gap in the youth psychotherapy
      field. In youth psychotherapy, alliance may be unidimensional, so establishing a
      strong bond and engaging the child in therapeutic activities may both be
      instrumental to establishing good alliance early in treatment. However, it is
      important to be cautious when interpreting the factor analytic findings, because
      the sample size may have been too small to identify additional factors. Future
      research can build upon these findings by examining the factor structure of youth
      alliance measures with larger, more diverse samples.

PMID- 22417198
TI  - Future directions for the study of suicide and self-injury.

PMID- 22417199
TI  - The effect of strength training volume on satellite cells, myogenic regulatory
      factors, and growth factors.
AB  - The aim of this work was to study the effect of training volume on activation of
      satellite cells. Healthy untrained men were randomly assigned into two groups.
      The 3L-1UB group (n = 10) performed three-set leg exercises and single-set upper
      body exercises, and the 1L-3UB group (n = 11) performed single-set leg exercises
      and three-set upper body exercises. Both groups performed three sessions (80-90
      min) per week for 11 weeks. Biopsies were taken from m. vastus lateralis and m.
      trapezius. The number of satellite cells, satellite cells positive for myogenin
      and MyoD, and the number of myonuclei were counted. Homogenized muscle was
      analyzed for myogenin and MyoD, and extracted ribonucleic acid (RNA) was
      monitored for selected growth factor transcripts. Knee extensor strength
      increased more in the 3L-1UB group than in the 1L-3UB group (48 +/- 4% vs 29 +/-
      4%), whereas the strength gain in shoulder press was similar in both training
      groups. The number of satellite cells in m. vastus lateralis increased more in
      the 3L-1UB group than in the 1L-3UB group. The number of myonuclei increased
      similarly in both groups. The messenger RNA expression of growth factors peaked
      after 2 weeks of training. In conclusion, increasing training volume enhanced
      satellite cell numbers in the leg muscle, but not in the upper body muscle.

PMID- 22417200
TI  - The Joint Commission's new tobacco-cessation measures--will hospitals do the
      right thing?

PMID- 22417201
TI  - Clonal architecture of secondary acute myeloid leukemia.
AB  - BACKGROUND: The myelodysplastic syndromes are a group of hematologic disorders
      that often evolve into secondary acute myeloid leukemia (AML). The genetic
      changes that underlie progression from the myelodysplastic syndromes to secondary
      AML are not well understood. METHODS: We performed whole-genome sequencing of
      seven paired samples of skin and bone marrow in seven subjects with secondary AML
      to identify somatic mutations specific to secondary AML. We then genotyped a bone
      marrow sample obtained during the antecedent myelodysplastic-syndrome stage from
      each subject to determine the presence or absence of the specific somatic
      mutations. We identified recurrent mutations in coding genes and defined the
      clonal architecture of each pair of samples from the myelodysplastic-syndrome
      stage and the secondary-AML stage, using the allele burden of hundreds of
      mutations. RESULTS: Approximately 85% of bone marrow cells were clonal in the
      myelodysplastic-syndrome and secondary-AML samples, regardless of the myeloblast
      count. The secondary-AML samples contained mutations in 11 recurrently mutated
      genes, including 4 genes that have not been previously implicated in the
      myelodysplastic syndromes or AML. In every case, progression to acute leukemia
      was defined by the persistence of an antecedent founding clone containing 182 to
      660 somatic mutations and the outgrowth or emergence of at least one subclone,
      harboring dozens to hundreds of new mutations. All founding clones and subclones
      contained at least one mutation in a coding gene. CONCLUSIONS: Nearly all the
      bone marrow cells in patients with myelodysplastic syndromes and secondary AML
      are clonally derived. Genetic evolution of secondary AML is a dynamic process
      shaped by multiple cycles of mutation acquisition and clonal selection. Recurrent
      gene mutations are found in both founding clones and daughter subclones. (Funded
      by the National Institutes of Health and others.).

PMID- 22417202
TI  - The severability of the individual mandate.

PMID- 22417204
TI  - Warning: contraceptive drugs may cause political headaches.

PMID- 22417203
TI  - Prognostic relevance of integrated genetic profiling in acute myeloid leukemia.
AB  - BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disease with respect
      to presentation and clinical outcome. The prognostic value of recently identified
      somatic mutations has not been systematically evaluated in a phase 3 trial of
      treatment for AML. METHODS: We performed a mutational analysis of 18 genes in 398
      patients younger than 60 years of age who had AML and who were randomly assigned
      to receive induction therapy with high-dose or standard-dose daunorubicin. We
      validated our prognostic findings in an independent set of 104 patients. RESULTS:
      We identified at least one somatic alteration in 97.3% of the patients. We found
      that internal tandem duplication in FLT3 (FLT3-ITD), partial tandem duplication
      in MLL (MLL-PTD), and mutations in ASXL1 and PHF6 were associated with reduced
      overall survival (P=0.001 for FLT3-ITD, P=0.009 for MLL-PTD, P=0.05 for ASXL1,
      and P=0.006 for PHF6); CEBPA and IDH2 mutations were associated with improved
      overall survival (P=0.05 for CEBPA and P=0.01 for IDH2). The favorable effect of
      NPM1 mutations was restricted to patients with co-occurring NPM1 and IDH1 or IDH2
      mutations. We identified genetic predictors of outcome that improved risk
      stratification among patients with AML, independently of age, white-cell count,
      induction dose, and post-remission therapy, and validated the significance of
      these predictors in an independent cohort. High-dose daunorubicin, as compared
      with standard-dose daunorubicin, improved the rate of survival among patients
      with DNMT3A or NPM1 mutations or MLL translocations (P=0.001) but not among
      patients with wild-type DNMT3A, NPM1, and MLL (P=0.67). CONCLUSIONS: We found
      that DNMT3A and NPM1 mutations and MLL translocations predicted an improved
      outcome with high-dose induction chemotherapy in patients with AML. These
      findings suggest that mutational profiling could potentially be used for risk
      stratification and to inform prognostic and therapeutic decisions regarding
      patients with AML. (Funded by the National Cancer Institute and others.).

PMID- 22417205
TI  - Profiles in leukemia.

PMID- 22417206
TI  - Respecting dignity in forensic care: the challenge faced by nurses of maintaining
      patient dignity in clinical caring situations.
AB  - We must recognize the importance of increased understanding for maintaining
      patient dignity to expand earlier formulated knowledge about caring ethics.
      Illuminations of this topic can create conditions for changing and developing
      care, as well as making caregivers' preservation of dignity evident. The aim was
      to illuminate the meaning of maintenance of patient dignity in forensic care. A
      qualitative design with a phenomenological-hermeneutic approach was used to
      analyse and interpret focus group interviews with nurses in forensic care. In the
      text the meaning of maintenance of patient dignity was protection and respect but
      also brotherly humanity. Protection was shown outwards to cover or screen the
      patient and to guard against danger. The inner form was described as protecting
      the patients' needs and arousing the patients' protection resources. Respect was
      shown outwards to take the patient seriously and to show others that patients are
      to be reckoned with, inwards in teaching patients to create respect and in
      teaching patients to expect respect from others. Meeting patients with human
      brotherhood was shown in doing 'the little extra' and demonstrating human
      similarity. The new understanding will enable nurses to plan and provide
      professional care, based on caring science.

PMID- 22417209
TI  - Asthma in children and nutritional selenium get another look.

PMID- 22417210
TI  - Anaphylaxis in Spain: where are the bees and other observations.

PMID- 22417211
TI  - 12-hydroxy-eicosatetraenoic acid (12-HETE): a biomarker of Churg-Strauss
      syndrome.
AB  - BACKGROUND: Churg-Strauss syndrome (CSS) shares similarities with asthma and
      hypereosinophilic syndrome (HES). Eicosanoids--important inflammatory and
      signaling molecules--are present in exhaled breath condensate (EBC) and broncho
      alveolar lavage fluid (BALF). OBJECTIVES: To assess eicosanoid profile both in
      EBC and BALF of CSS subjects searching for a pattern characteristic of this
      syndrome. METHODS: EBCs from 23 CSS patients, 30 asthmatics, 12 HES patients and
      54 healthy controls (HC) were assessed quantitatively for 19 eicosanoids by a
      high-performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS).
      In addition, in 21 of 23 CSS subjects and in nine asthmatics, eicosanoids were
      determined in BALF. RESULTS: EBC from CSS patients showed markedly elevated
      levels of 12-HETE as compared with other studied groups. BALF was characterized
      by a significant elevation of 12-HETE and its metabolite 12-tetranor HETE in CSS
      as compared with asthma. Clinical activity of CSS correlated with 12-HETE and its
      metabolites levels in BALF, but not in EBC. CONCLUSION AND CLINICAL RELEVANCE:
      CSS is clearly distinguished from bronchial asthma, and HES by a marked increase
      in 12-HETE concentration in both EBC and BALF. This points to a possible new
      pathogenic mechanism in CSS and may help in future in establishing the diagnosis
      of CSS.

PMID- 22417212
TI  - Probiotic effects on T-cell maturation in infants during weaning.
AB  - BACKGROUND: We previously reported that feeding the probiotic Lactobacillus
      paracasei ssp. paracasei F19 (LF19) during weaning reduced the cumulative
      incidence of eczema. OBJECTIVE: To investigate the impact of feeding LF19 on T
      cell maturation. METHODS: One hundred and seventy-nine healthy, term infants with
      no prior allergic manifestations were randomized to daily intake of cereals with
      (n = 89) or without (n = 90) the addition of LF19 10(8 ) colony forming units per
      serving from 4 to 13 months of age. Venous blood was drawn at 5.5 and 13 months
      of age. We used the cytokine response to polyclonal T-cell stimulation by anti
      CD3 plus anti-CD28 monoclonal antibodies, and in vitro stimulation with the
      vaccine tetanus toxoid (TT) as measures of global adaptive immunity and capacity
      to raise a specific T-cell response, respectively. Expression levels of IL-2, IFN
      gamma, IL-4, IL-17A and IL-10 messenger RNAs (mRNAs) were used as proxies for
      general T-cell stimulation and naive Th0 cells, Th1-, Th2-, Th17- and T
      regulatory lineages. RESULTS: There was no difference between the two groups at
      5.5 months of age. At 13 months, the polyclonal IL-2 response was higher in the
      placebo group (P < 0.05), whereas the IFN-gamma/IL-2 (P < 0.01) and IL-17A/IL-2
      (P < 0.05) ratios after polyclonal stimulation were higher in the probiotic
      group, as was the TT-specific IL17-A response (P < 0.001). In both groups, the
      IFN-gamma and IL-4 responses increased from 5.5 to 13 months upon both polyclonal
      and specific stimulation (P < 0.01), whereas the IL-10 response remained low (P >
      0.05). CONCLUSION AND CLINICAL RELEVANCE: Our findings suggest modest effects by
      probiotics on T-cell maturation following 9 months of probiotic intake. Future
      studies should address if specific probiotics may drive immune development with
      possible preventive effects on the development of allergic disease.

PMID- 22417207
TI  - Animal models of listeriosis: a comparative review of the current state of the
      art and lessons learned.
AB  - Listeriosis is a leading cause of hospitalization and death due to foodborne
      illness in the industrialized world. Animal models have played fundamental roles
      in elucidating the pathophysiology and immunology of listeriosis, and will almost
      certainly continue to be integral components of the research on listeriosis. Data
      derived from animal studies helped for example characterize the importance of
      cell-mediated immunity in controlling infection, allowed evaluation of
      chemotherapeutic treatments for listeriosis, and contributed to quantitative
      assessments of the public health risk associated with L. monocytogenes
      contaminated food commodities. Nonetheless, a number of pivotal questions remain
      unresolved, including dose-response relationships, which represent essential
      components of risk assessments. Newly emerging data about species-specific
      differences have recently raised concern about the validity of most traditional
      animal models of listeriosis. However, considerable uncertainty about the best
      choice of animal model remains. Here we review the available data on traditional
      and potential new animal models to summarize currently recognized strengths and
      limitations of each model. This knowledge is instrumental for devising future
      studies and for interpreting current data. We deliberately chose a historical,
      comparative and cross-disciplinary approach, striving to reveal clues that may
      help predict the ultimate value of each animal model in spite of incomplete data.

PMID- 22417213
TI  - Induction of GITRL expression in human keratinocytes by Th2 cytokines and TNF
      alpha: implications for atopic dermatitis.
AB  - BACKGROUND: Glucocorticoid-induced TNF receptor-related protein ligand (GITRL), a
      ligand for the T cell co-stimulatory molecule GITR, is expressed by keratinocytes
      and involved in chemokine production. The expression of GITRL in skin
      inflammation remains unknown. OBJECTIVES: This study investigated cytokine
      regulation of keratinocyte GITRL expression. METHODS: Glucocorticoid-induced TNF
      receptor expression was evaluated in cytokine-treated human epidermal
      keratinocytes (HEK)s, murine PAM 212 cell line, murine and human skin explants by
      real time PCR, flow cytometry and immunostaining. Functional responses to GITR
      fusion protein were examined by real time PCR and ELISA. GITRL expression in AD
      and psoriasis was studied by immunohistochemistry. RESULTS: Skin biopsies from
      STAT6VT transgenic mice, which develop spontaneous atopic skin inflammation, were
      found by immunofluoresence, to have increased keratinocyte GITRL expression.
      Exposure to Th2 cytokines augmented GITRL mRNA expression in the murine PAM 212
      keratinocytic cell line and murine skin explants. In contrast, GITRL mRNA and
      protein expression was only increased in HEKs and human skin explants in the
      presence of the combination of TNF-alpha and Th2 cytokines. A synergistic effect
      of Th2 cytokines and GITR fusion protein on production of CCL17, the Th2
      chemokine, by murine keratinocytes was demonstrated. Immunohistochemical staining
      showed that acute AD lesions have increased expression of GITRL compared with
      normal skin, chronic AD lesions and psoriatic plaques. CONCLUSIONS AND CLINICAL
      RELEVANCE: Our studies demonstrate that GITRL expression is augmented by Th2
      cytokines and TNF-alpha in keratinocytes. Increased GITRL expression in acute AD
      skin lesions is shown. This observation suggests a link between cytokine
      regulated keratinocyte GITRL expression and its role in inflammatory responses in
      AD.

PMID- 22417214
TI  - Selenium status and allergic disease in a cohort of New Zealand children.
AB  - BACKGROUND: New Zealand has one of the highest rates of asthma and atopy.
      Selenium has been implicated in the aetiology of asthma, and associations between
      low selenium status and asthma in New Zealand children have been reported.
      OBJECTIVE: The aim was to investigate the association between selenium status and
      allergic disease in a birth cohort of New Zealand children. METHODS: The New
      Zealand Asthma and Allergy Cohort Study is a prospective birth cohort in
      Wellington and Christchurch, involving 1105 infants born 1997-2001. During the 6
      year assessment (n = 635), associations were investigated between plasma selenium
      (PlSe) and whole blood glutathione peroxidase activity (WBGPx) and allergy
      related health outcomes including asthma, wheeze, hayfever, rhinitis, eczema and
      rash. RESULTS: Wellington children had greater PlSe and WBGPx than Christchurch
      children (P < 0.001 for both). PlSe (P = 0.004) and WBGPx (P = 0.03) were lower
      in children exposed to environmental smoke, but differences were no longer
      significant after adjustment for study location, current household smoking (5-6
      years), maternal smoking during pregnancy, family history (either parent with
      asthma, eczema or hayfever), prioritized ethnicity (Maori, Pacific peoples,
      Other, European), gender, season born, number of siblings, New Zealand
      Deprivation Index and body mass index at 6 years. Analysis of PlSe or WBGPx as
      continuous variables or of quartiles of PlSe with health outcomes showed no
      significant associations after adjustment. Univariate analysis of quartiles of
      PlSe and WBGPx with persistent wheeze showed significant inverse trends (P =
      0.005 for both), but these reduced after adjustment. CONCLUSIONS AND CLINICAL
      RELEVANCE: Our results do not support a strong association between selenium
      status and the high incidence of asthma in New Zealand. However, there was a
      modest association between lower PlSe and WBGPx activity and higher incidence of
      persistent wheeze.

PMID- 22417215
TI  - Anaphylaxis and reactions to foods in children--a population-based case study of
      emergency department visits.
AB  - BACKGROUND: Information about acute reactions to foods among children is limited.
      OBJECTIVE: To describe the overall incidence of anaphylaxis in a paediatric
      emergency department (ED) setting and to describe reactions to foods in relation
      to sex and age, clinical characteristics and management. METHODS: In a review of
      medical records, children with ED visits at any of three paediatric hospitals in
      Stockholm County during 2007 were targeted. Inclusion criteria were any adverse
      reaction to foods or anaphylaxis. RESULTS: 383 children fulfilled the inclusion
      criteria of which 371 had had reactions to foods. The incidence of anaphylaxis
      was 32 per 100 000 person years irrespective of cause and food was involved in
      92%. Tree nuts, particular cashew, and peanut were the most common eliciting
      foods, and in children under 3 years, reactions to these two food allergens were
      as common as reactions to milk and egg. Pollen-allergic children seemed to be
      admitted due to food-induced anaphylaxis more often during the deciduous tree
      pollen season compared with the rest of the year (P = 0.015). Symptoms from the
      lower airways occurred in 49% of children with anaphylaxis but without underlying
      asthma compared with 72% of children with anaphylaxis and asthma, P < 0.01.
      CONCLUSIONS AND CLINICAL RELEVANCE: Reactions to peanut and tree nuts are as
      common as reactions to milk and egg in early life. Concomitant exposure to
      airborne allergens seems to increase the risk of anaphylaxis to foods. Among
      children with anaphylaxis, wheeze is prevalent even in children without asthma
      diagnosis.

PMID- 22417216
TI  - Incidence of anaphylaxis in the city of Alcorcon (Spain): a population-based
      study.
AB  - BACKGROUND: Relatively few studies have examined the incidence of anaphylaxis in
      the general population. OBJECTIVE: To report the incidence of anaphylaxis among
      the general population of the city of Alcorcon, Spain, using various public
      health care databases. METHODS: Episodes of anaphylaxis were recovered using
      validated alphanumeric strings in different fields of electronic clinical records
      used in the different public health settings in the city of Alcorcon (primary
      care, Emergency Department, hospitalized patients and Allergy Outpatient Clinic).
      Patients with anaphylaxis were tracked across the different clinical settings in
      Alcorcon. RESULTS: The incidence of anaphylaxis in Alcorcon was 103.37 episodes
      per 100 000 person-years (total standardized incidence rate of 112.2). There was
      a peak of 313.58 episodes in the 0-4 years age group and a different distribution
      of incidence rates (although non-significant) among different age groups between
      male patients and female patients. In most age groups, incidence tended to be
      higher for female patients aged over 10 years. Patients were attended at two or
      more levels in 76.78% of episodes, and a new evaluation was often made at a
      primary care centre (71.43%), Allergy Outpatient Clinic (75.6%), or both after
      the episode (58.93%). CONCLUSION AND CLINICAL RELEVANCE: This study revealed a
      higher rate of anaphylaxis than that in previous studies, although this incidence
      rate is probably lower than the real incidence rate. Studies exploring potential
      methodological, genetic and environmental factors accounting for these higher
      rates of anaphylaxis are required.

PMID- 22417217
TI  - Molecular characterization of wheat allergens specifically recognized by patients
      suffering from wheat-induced respiratory allergy.
AB  - BACKGROUND: Wheat (Triticum aestivum) is an important allergen source responsible
      for various clinical manifestations of allergy (i.e. food allergy, pollen
      allergy, respiratory allergy to flour-Baker's asthma). OBJECTIVE: The objective
      of this study was the molecular and immunological characterization of new
      recombinant wheat allergens and to evaluate their usefulness for the diagnosis of
      allergy to wheat. METHODS: A T. aestivum cDNA library was constructed and
      screened with serum IgE from patients suffering from wheat allergy to identify
      cDNAs coding for new wheat allergens. The allergen-encoding cDNAs were expressed
      in Escherichia coli and purified to homogeneity. IgE reactivity of recombinant
      proteins was analysed in RAST-based, non-denaturing dot blot experiments and by
      ELISA with sera from wheat allergic patients and their allergenic activity was
      assessed in basophil degranulation experiments. RESULTS: We report the molecular
      characterization, recombinant expression and purification of five wheat
      allergens, a thioredoxin h isoform, glutathione transferase, 1-Cys-peroxiredoxin,
      profilin and dehydrin. Homologous proteins were identified by sequence
      comparisons in various plants. 1-Cys-peroxiredoxin appeared to be the most
      relevant of the newly identified wheat allergens according to prevalence of IgE
      recognition and results from basophil degranulation experiments. It showed IgE
      cross-reactivity with seed proteins from barley, rye, rice, maize, soy, oat and
      spelt. 1-Cys-peroxiredoxin, glutathione transferase and dehydrin were mainly
      recognized by patients with baker's asthma but not wheat-induced food allergy.
      CONCLUSION AND CLINICAL RELEVANCE: The characterized recombinant wheat allergens
      may be useful for the development of serological tests which allow the
      discrimination of different clinical manifestations of wheat allergy.

PMID- 22417221
TI  - Features and challenges of personality disorders in late life.

PMID- 22417220
TI  - Hypoxia-selective, enzymatic conversion of 6-nitroquinoline into a fluorescent
      helicene: pyrido[3,2-f]quinolino[6,5-c]cinnoline 3-oxide.
AB  - Regions of low oxygen concentration (hypoxia) occur in both normal human
      physiology and under pathophysiological conditions. Fluorescent probes for the
      direct imaging of cellular hypoxia could be useful tools that complement
      radiochemical imaging and immunohistochemical staining methods. In this work, we
      set out to characterize the hypoxia-selective enzymatic metabolism of a simple
      nitroaryl probe, 6-nitroquinoline (1). We envisioned that this compound might
      undergo hypoxia-selective, bioreductive conversion to the fluorescent product, 6
      aminoquinoline (2). The probe 1 was, indeed, converted to a fluorescent product
      selectively under hypoxic conditions by the one-electron reducing enzyme
      NADPH:cytochrome P450 reductase. However, inspection of the fluorescence spectrum
      and LC-MS analysis of the reaction mixture revealed that the expected product 2
      was not formed. Rather, the 63-fold increase in fluorescence emission at 445 nm
      resulting from the hypoxic metabolism of 1 was due to formation of the azoxy
      helicene product, pyrido[3,2-f]quinolino[6,5-c]cinnoline 3-oxide (4). The
      generation of 4 involves an unusual biaryl bond formation under reductive
      conditions. The mechanism of this process remains uncertain but could proceed via
      combination of a nitroaryl radical anion with a neutral nitrosoaryl radical,
      followed by tautomerization and intramolecular condensation between the resulting
      hydroxylamine and nitroso functional groups. Bioreductive metabolism of nitroaryl
      compounds represents a promising strategy for the selective delivery of cytotoxic
      agents and fluorescent markers to hypoxic tissue, but the results described here
      provide an important glimpse of the chemical complexity that can be associated
      with the enzymatic one-electron reduction of nitroaryl compounds.

PMID- 22417222
TI  - Topical timolol for infantile hemangioma of the eyelid.

PMID- 22417224
TI  - Plasma levels of midkine (neurite growth-promoting factor 2) are not associated
      with plasma fibrinolytic potential or risk of venous thrombosis.

PMID- 22417223
TI  - Clinical significance of serological biomarkers and neuropsychological
      performances in patients with temporal lobe epilepsy.
AB  - BACKGROUND: Temporal lobe epilepsy (TLE) is a common form of focal epilepsy.
      Serum biomarkers to predict cognitive performance in TLE patients without
      psychiatric comorbidities and the link with gray matter (GM) atrophy have not
      been fully explored. METHODS: Thirty-four patients with TLE and 34 sex - and age
      matched controls were enrolled for standardized cognitive tests, neuroimaging
      studies as well as measurements of serum levels of heat shock protein 70 (HSP70),
      S100beta protein (S100betaP), neuronal specific enolase (NSE), plasma nuclear and
      mitochondrial DNA levels. RESULTS: Compared with the controls, the patients with
      TLE had poorer cognitive performances and higher HSP70 and S100betaP levels (p <
      0.01). The patients with higher frequencies of seizures had higher levels of
      HSP70, NSE and S100betaP (p < 0.01). Serum HSP70 level correlated positively with
      duration of epilepsy (sigma = 0.413, p < 0.01), and inversely with memory scores
      in the late registration (sigma = -0.276, p = 0.01) and early recall score (sigma
      = -0.304, p = 0.007). Compared with the controls, gray matter atrophy in the
      hippocampal and parahippocampal areas, putamen, thalamus and supplementary motor
      areas were found in the patient group. The HSP70 levels showed an inverse
      correlation with hippocampal volume (R square = 0.22, p = 0.007) after
      controlling for the effect of age. CONCLUSIONS: Our results suggest that serum
      biomarkers were predictive of higher frequencies of seizures in the TLE group.
      HSP70 may be considered to be a stress biomarker in patients with TLE in that it
      correlated inversely with memory scores and hippocampal volume. In addition, the
      symmetric extratemporal atrophic patterns may be related to damage of neuronal
      networks and epileptogenesis in TLE.

PMID- 22417227
TI  - Role of solvation dynamics in excited state proton transfer of 1-naphthol in
      nanoscopic water clusters formed in a hydrophobic solvent.
AB  - Excited state proton transfer (ESPT) in biologically relevant organic molecules
      in aqueous environments following photoexcitation is very crucial as the
      reorganization of polar solvents (solvation) in the locally excited (LE) state of
      the organic molecule plays an important role in the overall rate of the ESPT
      process. A clear evolution of the two photoinduced dynamics in a model ESPT probe
      1-naphthol (NpOH) upon ultrafast photoexcitation is the motive of the present
      study. Herein, the detailed kinetics of the ESPT reaction of NpOH in water
      clusters formed in hydrophobic solvent are investigated. Distinct values of time
      constants associated with proton transfer and solvent relaxation have been
      achieved through picosecond-resolved fluorescence measurements. We have also used
      a model solvation probe Coumarin 500 (C500) to investigate the dynamics of
      solvation in the same environmental condition. The temperature dependent
      picosecond-resolved measurement of ESPT of NpOH and the dynamics of solvation
      from C500 identify the magnitude of intermolecular hydrogen bonding energy in the
      water cluster associated with the ultrafast ESPT process.

PMID- 22417225
TI  - Comparison of distribution- and anchor-based approaches to infer changes in
      health-related quality of life of prostate cancer survivors.
AB  - OBJECTIVE: To determine the minimal important difference (MID) in generic and
      prostate-specific health-related quality of life (HRQoL) using distribution- and
      anchor-based methods. STUDY DESIGN AND SETTING: Prospective cohort study of 602
      newly diagnosed prostate cancer patients recruited from an urban academic
      hospital and a Veterans Administration hospital. Participants completed generic
      (SF-36) and prostate-specific HRQoL surveys at baseline and at 3, 6, 12, and 24
      months posttreatment. Anchor-based and distribution-based methods were used to
      develop MID estimates. We compared the proportion of participants returning to
      baseline based on MID estimates from the two methods. RESULTS: MID estimates
      derived from combining distribution- and anchor-based methods for the SF-36
      subscales are physical function = 7, role physical = 14, role emotional = 12,
      vitality = 9, mental health = 6, social function = 9, bodily pain = 9, and
      general health = 8; and for the prostate-specific scales are urinary function =
      8, bowel function = 7, sexual function = 8, urinary bother = 9, bowel bother = 8,
      and sexual bother = 11. Proportions of participants returning to baseline values
      corresponding to MID estimates from the two methods were comparable. CONCLUSIONS:
      This is the first study to assess the MID for generic and prostate-specific HRQoL
      using anchor-based and distribution-based methods. Although variation exists in
      the MID estimates derived from these two methods, the recovery patterns
      corresponding to these estimates were comparable.

PMID- 22417228
TI  - Gastrocnemius muscle herniation as a rare differential diagnosis of ankle sprain:
      case report and review of the literature.
AB  - BACKGROUND: Muscle herniation of the leg is a rare clinical entity. Yet, knowing
      this condition is necessary to avoid misdiagnosis and delayed treatment. In the
      extremities, muscle herniation most commonly occurs as a result of an acquired
      fascial defect, often due to trauma. Different treatment options for symptomatic
      extremity muscle herniation in the extremities, including conservative treatment,
      fasciotomy and mesh repair have been described. CASE PRESENTATION: We present the
      case of a patient who presented with prolonged symptoms after an ankle sprain.
      The clinical picture showed a fascial insufficiency with muscle bulging under
      tension. Ultrasound and MRI imaging confirmed the diagnosis of muscle hernia of
      the medial gastrocnemius on the right leg. Conservative treatment did not lead to
      success. Therefore, the fascial defect was treated surgically by repairing the
      muscle herniation using a synthetic vicryl propylene patch. CONCLUSIONS: Muscle
      hernias should be taken into consideration as a rare differential diagnosis
      whenever patients present with persisting pain or soft tissue swelling after
      ankle sprain. Diagnosis is mainly based on clinical aspect and physical
      examination, but can be confirmed by radiologic imaging techniques, including
      (dynamic) ultrasound and MRI. If conservative treatment fails, we recommend the
      closure with mesh patches for large fascial defects.

PMID- 22417229
TI  - Unilateral renal agenesis and urethral atresia associated with ergotamine intake
      during pregnancy.
AB  - Ergotamine, an ergot alkaloid, used for the treatment and prevention of migraine
      attacks, is considered as a teratogenic drug and, therefore, should be avoided in
      pregnancy. Here, we report a newborn infant with unilateral renal agenesis,
      urethral atresia, and pulmonary hypoplasia associated with the use of ergotamine
      for the treatment of migraine attacks at early pregnancy. Genitourinary anomalies
      in association with ergotamine usage were rarely reported and this was the third
      case of renal agenesia in association with ergotamine usage in literature. We
      suggest that ergotamine teratogenicity may be dose dependent and should be
      avoided in pregnancy for the possibility of genitourinary anomalies.

PMID- 22417230
TI  - Problems with non-adherence to antipsychotic medication in Samoan New Zealanders:
      a literature review.
AB  - This paper explores what is known about adherence to antipsychotic medications in
      general and the possible reasons for non-adherence in Samoan New Zealanders.
      Samoan New Zealanders are either Samoan-born immigrants or their descendents born
      in New Zealand. Clinicians recognize a high prevalence of non-adherence among
      Samoan New Zealanders. The authors hypothesize that traditional Samoan beliefs
      play a prominent role in problems with adherence. To investigate this hypothesis,
      a review of the literature on adherence in Samoan New Zealanders was undertaken.
      Documents from the Ministry of Health support the hypothesis. To investigate this
      issue, the Ministry of Health initiated a qualitative research project to examine
      the nature of Samoan traditional beliefs. The results of this study are
      summarized. No research had previously been undertaken on adherence in Samoan New
      Zealanders. In general, there is a lack of research on all aspects of the mental
      health of Pacific peoples in New Zealand. Literature reviews of adherence
      research consistently show that interventions that improve adherence address the
      beliefs, behaviours, and relationships surrounding adherence. This finding
      supports the author's hypothesis that traditional beliefs play an important role
      in the problem of adherence. Further definitive study with Samoan New Zealanders
      is required.

PMID- 22417231
TI  - A synthetic model of the putative Fe(II)-iminobenzosemiquinonate intermediate in
      the catalytic cycle of o-aminophenol dioxygenases.
AB  - The oxidative ring cleavage of aromatic substrates by nonheme Fe dioxygenases is
      thought to involve formation of a ferrous-(substrate radical) intermediate. Here
      we describe the synthesis of the trigonal-bipyramdial complex
      Fe((Ph2)Tp)(ISQ(tBu)) (2), the first synthetic example of an iron(II) center
      bound to an iminobenzosemiquinonate (ISQ) radical. The unique electronic
      structure of this S = 3/2 complex and its one-electron oxidized derivative
      ([3](+)) have been established on the basis of crystallographic, spectroscopic,
      and computational analyses. These findings further demonstrate the viability of
      Fe(2+)-ISQ intermediates in the catalytic cycles of o-aminophenol dioxygenases.

PMID- 22417232
TI  - Sensitivity to probabilistic orthographic cues to lexical stress in adolescent
      speakers with autism spectrum disorder and typical peers.
AB  - Lexical stress refers to the opposition of strong and weak syllables within
      polysyllabic words and is a core feature of the English prosodic system. There
      are probabilistic cues to lexical stress present in English orthography. For
      example, most disyllabic English words ending with the letters "-ure" have first
      syllable stress (e.g., "pasture", but note words such as "endure"), whereas most
      ending with "-ose" have second-syllable stress (e.g., "propose", but note
      examples such as "glucose"). Adult native speakers of English are sensitive to
      these probabilities during silent reading. During testing, they tend to assign
      first-syllable stress when reading a nonword such as "lenture" but second
      syllable stress when reading "fostpose" (Arciuli & Cupples,  2006 ). Difficulties
      with prosody, including problems processing lexical stress, are a notable feature
      of autism spectrum disorder (ASD). The current study investigated the ability of
      adolescents with ASD (13-17 years of age) to show this sensitivity compared with
      a group of typically developing peers. Results indicated reduced sensitivity to
      probabilistic cues to lexical stress in the group with ASD. The implications of
      these findings are discussed.

PMID- 22417233
TI  - Direct arylation of imidazo[1,2-a]pyridine at C-3 with aryl iodides, bromides,
      and triflates via copper(I)-catalyzed C-H bond functionalization.
AB  - A convenient method for the copper(I)-catalyzed arylation of substituted
      imidazo[1,2-a]pyridine has been developed. This method is applicable to a variety
      of aryl electrophiles, including bromides, iodides, and triflates. It represents
      the first general process for C-3 arylation of substituted imidazo[1,2-a]pyridine
      by Cu(I) catalysis to construct various functionalized imidazo[1,2-a]pyridine
      core pi-systems.

PMID- 22417234
TI  - A simple strategy for screening for glucose intolerance, using glycated
      haemoglobin, in individuals admitted with acute coronary syndrome.
AB  - Glucose intolerance is common but often remains undiagnosed and untreated in
      people with acute coronary syndrome. The best approach to screening for glucose
      intolerance post-acute coronary syndrome remains debated. The World Health
      Organization has recently advocated the use of HbA(1c) in diagnosing Type 2
      diabetes. A screening strategy using HbA(1c) as the preferred test would be
      pragmatic and improve early detection and management of glucose intolerance in
      acute coronary care practice. In this commentary, we discuss the relevant
      literature and guidelines in this area and propose a simple and pragmatic
      algorithm based on the use of HbA(1c) to screen for glucose intolerance during
      and after admission with acute coronary syndrome.

PMID- 22417235
TI  - Self-reported and measured cardiorespiratory fitness similarly predict
      cardiovascular disease risk in young adults.
AB  - We aimed to (a) examine the validity and reliability of the International FItness
      Scale (IFIS) in Spanish young adults and (b) compare the capacity of self
      reported vs measured fitness to predict cardiovascular disease (CVD) risk. The
      study comprised 276 participants (18-30 years). Fitness level (overall and
      specific components) was both self-reported (IFIS) and measured using standard
      fitness tests. Total and trunk fat was assessed by dual-energy X-ray
      absorptiometry. We computed a previously validated metabolic syndrome score. A
      separate sample of 181 of same age and characteristics fulfilled IFIS twice for
      reliability purposes. The results of the present study support the validity and
      reliability of self-reported fitness, as measured by IFIS, in Spanish young
      adults. Our data also suggest that not only measured cardiorespiratory fitness
      but also self-reported cardiorespiratory fitness predicts CVD risk, as assessed
      by adiposity and metabolic syndrome indicators. The associations for muscular
      fitness (both reported and measured) differed depending on how it was expressed
      (i.e., absolute vs relative terms). Self-reported fitness, as assessed by IFIS,
      can be a good alternative when physical fitness cannot be measured in large
      surveys.

PMID- 22417236
TI  - Folding models of mini-protein FSD-1.
AB  - We have carried out all-atom action-derived molecular dynamics (ADMD) folding
      simulations of the full-size FSD-1. FSD-1 is a designed mini-protein of 28
      residues containing both alpha and beta secondary structure elements. Multiple
      folding pathways are found for FSD-1, which is consistent with existing
      computational studies. Hydrophobic collapse is observed first, and then
      subsequent folding events proceeds by forming either alpha-helix or beta-hairpin.
      Concurrent formation of the full tertiary structure and the secondary structure
      elements of alpha-helix and beta-hairpin is observed. The folding pathway of FSD
      1 elucidated by ADMD simulations does not follow the scenario of the framework
      model. ADMD simulations provide significant insights for the general mechanisms
      of protein folding and conformational changes.

PMID- 22417238
TI  - Flail-arm variant of amyotrophic lateral sclerosis in a Spanish soccer player.

PMID- 22417239
TI  - Ocular motor deficits in oculopharyngeal muscular dystrophy.

PMID- 22417241
TI  - Workplace accommodations and unmet needs specific to individuals who are deaf or
      hard of hearing.
AB  - PURPOSE: The purpose of this paper is to identify the workplace accommodations
      used by individuals who are deaf or hard of hearing, to report the perceived
      impact of the accommodations and to identify unmet needs with respect to
      workplace accommodations. METHOD: Individuals who are deaf or hard of hearing
      participated in an online survey. Respondents identified with one of four levels
      of functional hearing ability and selected from descriptions of workplace
      accommodations. Each selection was ranked according to perceived importance,
      satisfaction and frequency of use. Respondents also commented on unmet needs.
      RESULTS: The most common accommodations were telephone aids (55%), co-worker
      helps (34%) and electronic communication (31%). Importance and frequency of use
      ranked high among most respondents (76% and 87%, respectively). However,
      perceived satisfaction ranked high among only 50% of respondents. The most common
      unmet needs were effective communication in groups and lack of co-worker support.
      CONCLUSIONS: Workplace accommodations are viewed as important and frequently used
      by individuals who are deaf or hard of hearing. However, satisfaction with the
      accommodations is marginal at best. Unmet needs remain in the areas of
      communication in meetings, support of co-workers and the development of a more
      universally accessible workplace environment.

PMID- 22417243
TI  - Why don't northern American solutions to drinking and driving work in southern
      America?
AB  - While individual studies from several South American countries have shown driving
      while intoxicated to be a problem, there are no objective systematically
      collected alcohol-associated driving data obtained in most South American
      countries. This limits their ability to implement and enforce targeted prevention
      strategies, evaluate whether proven prevention efforts from North America
      (particularly the United States and Canada) can be transferred to the South, and
      to sustain momentum for the improvement of road safety by demonstrating that
      previously implemented legal and policy changes are effective. The aim of this
      paper is to discuss the abysmal differences that exist between northern and
      southern American countries regarding the current status of driving while
      intoxicated prevention strategies-their implementation, impacts and effects-using
      Brazil as a case example. We propose a three-pronged approach to close this
      northern-southern American gap in driving while intoxicated prevention and
      intervention: (a) systematic collection on road traffic crash/injury/death as
      well as risk factor data, (b) passage of laws without loopholes requiring
      compliance with blood alcohol concentration testing and (c) provision of
      appropriate training and equipment to the police in concomitance with vigilant
      enforcement. Resources and energies must be put towards data collection,
      implementation of prevention strategies and enforcement in order to decrease the
      unacceptably high rates of these preventable driving while intoxicated deaths.

PMID- 22417244
TI  - T lymphocyte insensitivity to corticosteroids in chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: There are increased numbers of activated lymphocytes in the lungs of
      chronic obstructive pulmonary disease (COPD) patients. The clinical benefits of
      corticosteroids in COPD patients are limited. Our hypothesis is that lymphocytes
      play a role in this corticosteroid insensitivity. OBJECTIVES: To investigate the
      effects of the corticosteroid dexamethasone on lung lymphocyte cytokine
      production from patients with COPD compared to controls. METHODS: Cultured airway
      lymphocytes obtained by bronchoscopy from healthy non-smokers (HNS), smokers (S)
      and COPD patients were stimulated with phytohaemagglutinin (PHA) & phorbol
      myristate acetate (PMA), +/- dexamethasone. Supernatants were assayed for
      interleukin (IL)-2 and interferon (IFN)gamma. Immunofluoresence was used to
      analyse changes in CD8 glucocorticoid receptor (GRalpha and GRbeta) expression.
      RESULTS: The inhibition of PHA/PMA stimulated IFNgamma production by
      dexamethasone was reduced in COPD patients compared to HNS (p < 0.05 at
      concentrations from 0.1-1 MUM). There was also a significant reduction (p < 0.05)
      in the mean inhibitory effect at 1 MUM in COPD patients (54.1%) compared to
      smokers (72.1%), and in smokers compared to HNS (85.5%). There was a numerically
      reduced effect of dexamethasone on IL-2 production that did not reach statistical
      significance. There was no difference in GRalpha and GRbeta expression in
      follicular CD8 cells between COPD patients (50.9% and 30.4% respectively) and
      smokers (52.9% and 29.7% respectively). CONCLUSIONS: IFNgamma production from
      COPD airway lymphocytes is corticosteroid insensitive. This phenomenon may be
      important in the poor clinical response often observed with corticosteroids.

PMID- 22417245
TI  - Downregulation of circulating CD4+ CD25(bright) Foxp3+ T cells by cyclosporine
      therapy and correlation with clinical response in psoriasis patients: report of
      three cases.

PMID- 22417246
TI  - Private dentists assess treatment required as more extensive, demanding and
      costly, than public sector dentists.
AB  - OBJECTIVES: The aim was to evaluate whether contracted private practitioners
      assess required treatment more extensive, demanding and economically more
      rewarding than mainly salaried public sector dentists and to estimate the cost
      consequences of using these alternative providers. METHODS: All dental services
      included in comprehensive treatments funded by the city of Turku and provided to
      adult patients during the year 2009 were recorded. Patients were distributed
      randomly without any determination of treatment needs before appointing them to
      different dentists. Treatment courses for 7432 patients in public clinics
      included 63 906 procedures and for 2932 patients assigned to treatment by
      contracted private practitioners included 21 194 procedures. Public sector
      dentists were mainly salaried with production incentives, and private
      practitioners worked purely on a fee-for-service basis. The cost estimates were
      based on the distributions of competence classifications recorded by the
      providers, which also formed the basis for reimbursement. RESULTS: For each
      studied treatment category with more than one competence classification, private
      contractors were less likely than their public sector counterparts to give an
      assessment of simple or less demanding: 8% versus 29% of examinations, 46% versus
      69% of periodontal treatments, 63% versus 85% of extractions, 31% versus 46% of
      fillings, 18% versus 35% of root canals. The excess cost to society varied from
      7.0% for root canal treatments to 21.3% for extractions, causing on average 14.4%
      higher cost level from use of private practitioners compared with public sector
      dentists. CONCLUSIONS: Private practitioners systematically classified the
      treatment procedures they provided as more demanding, and therefore more
      economically rewarding, than their public sector counterparts. The findings
      indicate that the costs of publicly funded dental care may be increased by the
      use of private dental contractors.

PMID- 22417248
TI  - Treatment with unlabeled mAb BR96 after radioimmunotherapy with 177Lu-DOTA-BR96
      in a syngeneic rat colon carcinoma model.
AB  - Metastatic disease after successful treatment of the primary tumor continues to
      be a therapeutic challenge. Enhancement of therapeutic effects by the
      administration of unlabeled monoclonal antibodies (mAbs) after radioimmunotherapy
      (RIT) may provide a means of preventing or delaying the development of metastatic
      disease. In the present study, Brown Norway rats with syngeneic grafted colon
      carcinomas were administered the minimal effective therapeutic dose of 400 MBq/kg
      lutetium-177 ((177)Lu)-DOTA-BR96. After 2 weeks, half of the animals were given
      15 mg/kg unlabeled mAb BR96 as consolidation therapy. Treatment response and
      toxicity were monitored 100 days after the treatment with unlabeled BR96. The
      treatment with unlabeled mAb after RIT resulted in a complete response (CR) in 19
      of 19 animals, while RIT alone resulted in a CR in 17 of 19 animals. The
      additional treatment did not affect the number of animals with metastatic disease
      or the time to clinical symptoms of metastases. RIT resulted in reversible
      myelotoxicity. The unlabeled mAb BR96 did not cause any additional toxicity,
      making it possible to repeat the consolidation therapy.

PMID- 22417247
TI  - An update on the strategies in multicomponent activity monitoring within the
      phytopharmaceutical field.
AB  - BACKGROUND: To-date modern drug research has focused on the discovery and
      synthesis of single active substances. However, multicomponent preparations are
      gaining increasing importance in the phytopharmaceutical field by demonstrating
      beneficial properties with respect to efficacy and toxicity. DISCUSSION: In
      contrast to single drug combinations, a botanical multicomponent therapeutic
      possesses a complex repertoire of chemicals that belong to a variety of substance
      classes. This may explain the frequently observed pleiotropic bioactivity spectra
      of these compounds, which may also suggest that they possess novel therapeutic
      opportunities. Interestingly, considerable bioactivity properties are exhibited
      not only by remedies that contain high doses of phytochemicals with prominent
      pharmaceutical efficacy, but also preparations that lack a sole active principle
      component. Despite that each individual substance within these multicomponents
      has a low molar fraction, the therapeutic activity of these substances is
      established via a potentialization of their effects through combined and
      simultaneous attacks on multiple molecular targets. Although beneficial
      properties may emerge from such a broad range of perturbations on cellular
      machinery, validation and/or prediction of their activity profiles is accompanied
      with a variety of difficulties in generic risk-benefit assessments. Thus, it is
      recommended that a comprehensive strategy is implemented to cover the entirety of
      multicomponent-multitarget effects, so as to address the limitations of
      conventional approaches. SUMMARY: An integration of standard toxicological
      methods with selected pathway-focused bioassays and unbiased data acquisition
      strategies (such as gene expression analysis) would be advantageous in building
      an interaction network model to consider all of the effects, whether they were
      intended or adverse reactions.

PMID- 22417249
TI  - Pulmonary embolism in sickle cell disease: a case-control study.
AB  - INTRODUCTION: A pulmonary embolism (PE) is a leading cause of mortality in
      hospitalized patients, yet the prevalence of PE in sickle cell disease (SCD) and
      its relation to disease severity or intrinsic hypercoagulability are not
      established. METHODS: We estimated inpatient PE incidence and prevalence among
      SCD and non-SCD populations in Pennsylvania, and compared severity of illness and
      mortality, using Pennsylvania Health Care Cost Containment Council (PHC4)
      discharge data, 2001-2006. Risk factors for PE were assessed in a case-control
      study of discharges from the University of Pittsburgh Medical Archival Records
      System (MARS). RESULTS: The incidence of inpatient PE was higher in the SCD PA
      population than in the non-SCD Pennsylvania population, 2001-2006. The PE
      prevalence among SCD discharges <= 50 years of age, 0.57%, was similar to that in
      non-SCD Pennsylvania discharges, 0.60%, and unchanged after adjustment for race.
      Among SCD discharges, those developing PE were significantly older, with a longer
      length of stay, greater severity of illness and higher mortality, P < 0.001, than
      SCD without a PE. Among PE discharges, SCD had a similar severity of illness, P =
      0.77, and mortality, P = 0.39, but underwent fewer computerized tomographic
      scans, P = 0.006, than non-SCD with PE. In the local case-control study, no
      clinical or laboratory feature was associated with PE. CONCLUSIONS: The incidence
      of PE is higher and chest computed tomography (CT) utilization is lower in SCD
      than non-SCD inpatients, suggesting that PE may be under-diagnosed.

PMID- 22417250
TI  - Major trends in the U.S. health economy since 1950.

PMID- 22417251
TI  - Prostate-cancer mortality at 11 years of follow-up.
AB  - BACKGROUND: Several trials evaluating the effect of prostate-specific antigen
      (PSA) testing on prostate-cancer mortality have shown conflicting results. We
      updated prostate-cancer mortality in the European Randomized Study of Screening
      for Prostate Cancer with 2 additional years of follow-up. METHODS: The study
      involved 182,160 men between the ages of 50 and 74 years at entry, with a
      predefined core age group of 162,388 men 55 to 69 years of age. The trial was
      conducted in eight European countries. Men who were randomly assigned to the
      screening group were offered PSA-based screening, whereas those in the control
      group were not offered such screening. The primary outcome was mortality from
      prostate cancer. RESULTS: After a median follow-up of 11 years in the core age
      group, the relative reduction in the risk of death from prostate cancer in the
      screening group was 21% (rate ratio, 0.79; 95% confidence interval [CI], 0.68 to
      0.91; P=0.001), and 29% after adjustment for noncompliance. The absolute
      reduction in mortality in the screening group was 0.10 deaths per 1000 person
      years or 1.07 deaths per 1000 men who underwent randomization. The rate ratio for
      death from prostate cancer during follow-up years 10 and 11 was 0.62 (95% CI,
      0.45 to 0.85; P=0.003). To prevent one death from prostate cancer at 11 years of
      follow-up, 1055 men would need to be invited for screening and 37 cancers would
      need to be detected. There was no significant between-group difference in all
      cause mortality. CONCLUSIONS: Analyses after 2 additional years of follow-up
      consolidated our previous finding that PSA-based screening significantly reduced
      mortality from prostate cancer but did not affect all-cause mortality. (Current
      Controlled Trials number, ISRCTN49127736.).

PMID- 22417254
TI  - Ingenol mebutate gel for actinic keratosis.
AB  - BACKGROUND: Actinic keratosis is a common precursor to sun-related squamous-cell
      carcinoma. Treating actinic keratoses and the surrounding skin area (i.e., field
      therapy) can eradicate clinical and subclinical actinic keratoses. Topical field
      therapy currently requires weeks or months of treatment. We investigated the
      efficacy and safety of a new topical field therapy for actinic keratosis, ingenol
      mebutate gel (0.015% for face and scalp and 0.05% for trunk and extremities).
      METHODS: In four multicenter, randomized, double-blind studies, we randomly
      assigned patients with actinic keratoses on the face or scalp or on the trunk or
      extremities to receive ingenol mebutate or placebo (vehicle), self-applied to a
      25-cm(2) contiguous field once daily for 3 consecutive days for lesions on the
      face or scalp or for 2 consecutive days for the trunk or extremities. Complete
      clearance (primary outcome) was assessed at 57 days, and local reactions were
      quantitatively measured. RESULTS: In a pooled analysis of the two trials
      involving the face and scalp, the rate of complete clearance was higher with
      ingenol mebutate than with placebo (42.2% vs. 3.7%, P<0.001). Local reactions
      peaked at day 4, with a mean maximum composite score of 9.1 on the local-skin
      response scale (which ranges from 0 to 4 for six types of reaction, yielding a
      composite score of 0 to 24, with higher numbers indicating more severe
      reactions), rapidly decreased by day 8, and continued to decrease, approaching
      baseline scores by day 29. In a pooled analysis of the two trials involving the
      trunk and extremities, the rate of complete clearance was also higher with
      ingenol mebutate than with placebo (34.1% vs. 4.7%, P<0.001). Local skin
      reactions peaked between days 3 and 8 and declined rapidly, approaching baseline
      by day 29, with a mean maximum score of 6.8. Adverse events were generally mild
      to moderate in intensity and resolved without sequelae. CONCLUSIONS: Ingenol
      mebutate gel applied topically for 2 to 3 days is effective for field treatment
      of actinic keratoses. (Funded by LEO Pharma; ClinicalTrials.gov numbers,
      NCT00742391, NCT00916006, NCT00915551, and NCT00942604.).

PMID- 22417255
TI  - Shattuck Lecture. A successful and sustainable health system--how to get there
      from here.

PMID- 22417256
TI  - Clinical practice. Uncomplicated urinary tract infection.

PMID- 22417257
TI  - Images in clinical medicine. Barium aspiration.

PMID- 22417253
TI  - Placebo-controlled trial of oral laquinimod for multiple sclerosis.
AB  - BACKGROUND: Two proof-of-concept clinical trials have provided evidence that
      laquinimod reduces disease activity in patients with relapsing-remitting multiple
      sclerosis. METHODS: We conducted a randomized, double-blind, phase 3 study at 139
      sites in 24 countries. A total of 1106 patients with relapsing-remitting multiple
      sclerosis were randomly assigned in a 1:1 ratio to receive oral laquinimod at a
      dose of 0.6 mg once daily or placebo for 24 months. The primary end point was the
      annualized relapse rate during the 24-month period. Secondary end points included
      confirmed disability progression (defined as an increase in the score on the
      Expanded Disability Status Scale that was sustained for at least 3 months) and
      the cumulative number of gadolinium-enhancing lesions and new or enlarging
      lesions on T(2)-weighted magnetic resonance imaging. RESULTS: Treatment with
      laquinimod as compared with placebo was associated with a modest reduction in the
      mean (+/-SE) annualized relapse rate (0.30+/-0.02 vs. 0.39+/-0.03, P=0.002) and
      with a reduction in the risk of confirmed disability progression (11.1% vs.
      15.7%; hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; P=0.01). The
      mean cumulative numbers of gadolinium-enhancing lesions and new or enlarging
      lesions on T(2)-weighted images were lower for patients receiving laquinimod than
      for those receiving placebo (1.33+/-0.14 vs. 2.12+/-0.22 and 5.03+/-0.08 vs.
      7.14+/-0.07, respectively; P<0.001 for both comparisons). Transient elevations in
      alanine aminotransferase levels to greater than three times the upper limit of
      the normal range were observed in 24 patients receiving laquinimod (5%) and 8
      receiving placebo (2%). CONCLUSIONS: In this phase 3 study, oral laquinimod
      administered once daily slowed the progression of disability and reduced the rate
      of relapse in patients with relapsing-remitting multiple sclerosis. (Funded by
      Teva Pharmaceutical Industries; ClinicalTrials.gov number, NCT00509145.).

PMID- 22417252
TI  - Closure or medical therapy for cryptogenic stroke with patent foramen ovale.
AB  - BACKGROUND: The prevalence of patent foramen ovale among patients with
      cryptogenic stroke is higher than that in the general population. Closure with a
      percutaneous device is often recommended in such patients, but it is not known
      whether this intervention reduces the risk of recurrent stroke. METHODS: We
      conducted a multicenter, randomized, open-label trial of closure with a
      percutaneous device, as compared with medical therapy alone, in patients between
      18 and 60 years of age who presented with a cryptogenic stroke or transient
      ischemic attack (TIA) and had a patent foramen ovale. The primary end point was a
      composite of stroke or transient ischemic attack during 2 years of follow-up,
      death from any cause during the first 30 days, or death from neurologic causes
      between 31 days and 2 years. RESULTS: A total of 909 patients were enrolled in
      the trial. The cumulative incidence (Kaplan-Meier estimate) of the primary end
      point was 5.5% in the closure group (447 patients) as compared with 6.8% in the
      medical-therapy group (462 patients) (adjusted hazard ratio, 0.78; 95% confidence
      interval, 0.45 to 1.35; P=0.37). The respective rates were 2.9% and 3.1% for
      stroke (P=0.79) and 3.1% and 4.1% for TIA (P=0.44). No deaths occurred by 30 days
      in either group, and there were no deaths from neurologic causes during the 2
      year follow-up period. A cause other than paradoxical embolism was usually
      apparent in patients with recurrent neurologic events. CONCLUSIONS: In patients
      with cryptogenic stroke or TIA who had a patent foramen ovale, closure with a
      device did not offer a greater benefit than medical therapy alone for the
      prevention of recurrent stroke or TIA. (Funded by NMT Medical; ClinicalTrials.gov
      number, NCT00201461.).

PMID- 22417258
TI  - Case records of the Massachusetts General Hospital. Case 8-2012. A 53-year-old
      man with Crohn's disease, diarrhea, fever, and bacteremia.

PMID- 22417259
TI  - New data on prostate-cancer mortality after PSA screening.

PMID- 22417260
TI  - Patent foramen ovale closure--closing the door except for trials.

PMID- 22417262
TI  - SF3B1 in chronic lymphocytic leukemia.

PMID- 22417264
TI  - Catheter ablation for atrial fibrillation.

PMID- 22417265
TI  - Catheter ablation for atrial fibrillation.

PMID- 22417266
TI  - Catheter ablation for atrial fibrillation.

PMID- 22417267
TI  - Catheter ablation for atrial fibrillation.

PMID- 22417269
TI  - The road less traveled.

PMID- 22417270
TI  - The road less traveled.

PMID- 22417271
TI  - Ovarian toxicity from sirolimus.

PMID- 22417272
TI  - Pregnancy in a woman with a leptin-receptor mutation.

PMID- 22417276
TI  - Images in clinical medicine. Westermark sign in pulmonary embolism.

PMID- 22417277
TI  - Use of the Michigan Neuropathy Screening Instrument as a measure of distal
      symmetrical peripheral neuropathy in Type 1 diabetes: results from the Diabetes
      Control and Complications Trial/Epidemiology of Diabetes Interventions and
      Complications.
AB  - AIMS: The Michigan Neuropathy Screening Instrument (MNSI) is used to assess
      distal symmetrical peripheral neuropathy in diabetes. It includes two separate
      assessments: a 15-item self-administered questionnaire and a lower extremity
      examination that includes inspection and assessment of vibratory sensation and
      ankle reflexes. The purpose of this study was to evaluate the performance of the
      MNSI in detecting distal symmetrical peripheral neuropathy in patients with Type
      1 diabetes and to develop new scoring algorithms. METHODS: The MNSI was performed
      by trained personnel at each of the 28 Diabetes Control and Complications
      Trial/Epidemiology of Diabetes Interventions and Complications clinical sites.
      Neurologic examinations and nerve conduction studies were performed during the
      same year. Confirmed clinical neuropathy was defined by symptoms and signs of
      distal symmetrical peripheral neuropathy based on the examination of a
      neurologist and abnormal nerve conduction findings in >= 2 anatomically distinct
      nerves among the sural, peroneal and median nerves. RESULTS: We studied 1184
      subjects with Type 1 diabetes. Mean age was 47 years and duration of diabetes was
      26 years. Thirty per cent of participants had confirmed clinical neuropathy, 18%
      had >= 4 and 5% had >= 7 abnormal responses on the MNSI questionnaire, and 33%
      had abnormal scores (>= 2.5) on the MNSI examination. New scoring algorithms were
      developed and cut points defined to improve the performance of the MNSI
      questionnaire, examination and the combination of the two. CONCLUSIONS: Altering
      the cut point to define an abnormal test from >= 7 abnormal to >= 4 abnormal
      items improves the performance of the MNSI questionnaire. The MNSI is a simple,
      non-invasive and valid measure of distal symmetrical peripheral neuropathy in
      Type 1 diabetes.

PMID- 22417278
TI  - Effects of exposure on discrimination of similar stimuli and on memory for their
      unique and common features.
AB  - Human participants received exposure to similar visual stimuli (AW and BW) that
      shared a common feature (W). Experiment 1 demonstrated that subsequent
      discrimination between AW and BW was more accurate when the two stimuli were
      preexposed on an intermixed schedule (AW, BW, AW, BW...) than when they were
      preexposed on a blocked schedule (AW, AW...BW, BW...): the intermixed-blocked
      effect. Furthermore, memory for the unique features of the stimuli (A and B) was
      better when the stimuli were preexposed on an intermixed schedule than when they
      were preexposed on a blocked schedule. Conversely, memory for the common features
      of the stimuli (W) was better when the stimuli were preexposed on a blocked
      schedule than when they were preexposed on an intermixed schedule. Experiment 2
      again demonstrated the intermixed-blocked effect, but participants were
      preexposed to the stimuli in such a way that the temporal spacing between
      exposures to the unique features was equated between schedules. Memory for the
      unique and common features was similar to that found in Experiment 1. These
      findings support the proposal that perceptual learning depends on a mechanism
      that enhances memory for the unique features and reduces memory for common
      features.

PMID- 22417279
TI  - Visualisation of variable binding pockets on protein surfaces by probabilistic
      analysis of related structure sets.
AB  - BACKGROUND: Protein structures provide a valuable resource for rational drug
      design. For a protein with no known ligand, computational tools can predict
      surface pockets that are of suitable size and shape to accommodate a
      complementary small-molecule drug. However, pocket prediction against single
      static structures may miss features of pockets that arise from proteins' dynamic
      behaviour. In particular, ligand-binding conformations can be observed as
      transiently populated states of the apo protein, so it is possible to gain
      insight into ligand-bound forms by considering conformational variation in apo
      proteins. This variation can be explored by considering sets of related
      structures: computationally generated conformers, solution NMR ensembles,
      multiple crystal structures, homologues or homology models. It is non-trivial to
      compare pockets, either from different programs or across sets of structures. For
      a single structure, difficulties arise in defining particular pocket's
      boundaries. For a set of conformationally distinct structures the challenge is
      how to make reasonable comparisons between them given that a perfect structural
      alignment is not possible. RESULTS: We have developed a computational method,
      Provar, that provides a consistent representation of predicted binding pockets
      across sets of related protein structures. The outputs are probabilities that
      each atom or residue of the protein borders a predicted pocket. These
      probabilities can be readily visualised on a protein using existing molecular
      graphics software. We show how Provar simplifies comparison of the outputs of
      different pocket prediction algorithms, of pockets across multiple simulated
      conformations and between homologous structures. We demonstrate the benefits of
      use of multiple structures for protein-ligand and protein-protein interface
      analysis on a set of complexes and consider three case studies in detail: i)
      analysis of a kinase superfamily highlights the conserved occurrence of surface
      pockets at the active and regulatory sites; ii) a simulated ensemble of
      unliganded Bcl2 structures reveals extensions of a known ligand-binding pocket
      not apparent in the apo crystal structure; iii) visualisations of interleukin-2
      and its homologues highlight conserved pockets at the known receptor interfaces
      and regions whose conformation is known to change on inhibitor binding.
      CONCLUSIONS: Through post-processing of the output of a variety of pocket
      prediction software, Provar provides a flexible approach to the analysis and
      visualization of the persistence or variability of pockets in sets of related
      protein structures.

PMID- 22417280
TI  - Exercise for fitness does not decrease the muscular inactivity time during normal
      daily life.
AB  - The time spent in sedentary behaviors has been shown to be independent of
      exercise in epidemiological studies. We examined within an individual whether
      exercise alters the time of muscular inactivity within his/her normal daily life.
      Quadriceps and hamstring muscle electromyographic activities and heart rate were
      measured during 1 to 6 days of normal daily living of ordinary people. Of 84
      volunteers measured, 27 (15 men, 12 women, 40.7 years +/- 16.5 years) fulfilled
      the criteria of having at least 1 day with and 1 day without exercise for fitness
      (total of 87 days analyzed, 13.0 h +/- 2.5 h/day). Reported exercises varied from
      Nordic walking to strength training and ball games lasting 30 min-150 min (mean
      83 min +/- 30 min). Exercise increased the time spent at moderate-to-vigorous
      muscle activity (6% +/- 4% to 9% +/- 6%, P < 0.01) and energy expenditure (13% +/
      22%, P < 0.05). Muscular inactivity, defined individually below that measured
      during standing, comprised 72% +/- 12% of day without and 68% +/- 13% of day with
      exercise (not significant). Duration of exercise correlated positively to the
      increase in moderate-to-vigorous muscle activity time (r = 0.312, P < 0.05) but
      not with inactivity time. In conclusion, exercise for fitness, regardless of its
      duration, does not decrease the inactivity time during normal daily life. This is
      possible by slight modifications in daily nonexercise activities. 

PMID- 22417281
TI  - The effectiveness of chronic care management for heart failure: meta-regression
      analyses to explain the heterogeneity in outcomes.
AB  - OBJECTIVE: To support decision making on how to best redesign chronic care by
      studying the heterogeneity in effectiveness across chronic care management
      evaluations for heart failure. DATA SOURCES: Reviews and primary studies that
      evaluated chronic care management interventions. STUDY DESIGN: A systematic
      review including meta-regression analyses to investigate three potential sources
      of heterogeneity in effectiveness: study quality, length of follow-up, and number
      of chronic care model components. PRINCIPAL FINDINGS: Our meta-analysis showed
      that chronic care management reduces mortality by a mean of 18 percent (95
      percent CI: 0.72-0.94) and hospitalization by a mean of 18 percent (95 percent
      CI: 0.76-0.93) and improves quality of life by 7.14 points (95 percent CI: -9.55
      to -4.72) on the Minnesota Living with Heart Failure questionnaire. We could not
      explain the considerable differences in hospitalization and quality of life
      across the studies. CONCLUSION: Chronic care management significantly reduces
      mortality. Positive effects on hospitalization and quality of life were shown,
      however, with substantial heterogeneity in effectiveness. This heterogeneity is
      not explained by study quality, length of follow-up, or the number of chronic
      care model components. More attention to the development and implementation of
      chronic care management is needed to support informed decision making on how to
      best redesign chronic care.

PMID- 22417282
TI  - ZmbZIP60 mRNA is spliced in maize in response to ER stress.
AB  - BACKGROUND: Adverse environmental conditions produce ER stress and elicit the
      unfolded protein response (UPR) in plants. Plants are reported to have two "arms"
      of the ER stress signaling pathway-one arm involving membrane-bound transcription
      factors and the other involving a membrane-associated RNA splicing factor, IRE1.
      IRE1 in yeast to mammals recognizes a conserved twin loop structure in the target
      RNA. RESULTS: A segment of the mRNA encoding ZmbZIP60 in maize can be folded into
      a twin loop structure, and in response to ER stress this mRNA is spliced,
      excising a 20b intron. Splicing converts the predicted protein from a membrane
      associated transcription factor to one that is targeted to the nucleus. Splicing
      of ZmbZIP60 can be elicited in maize seedlings by ER stress agents such as
      dithiothreitol (DTT) or tunicamycin (TM) or by heat treatment. Younger, rather
      than older seedlings display a more robust splicing response as do younger parts
      of leaf, along a developmental gradient in a leaf. The molecular signature of an
      ER stress response in plants includes the upregulation of Binding Protein (BIP)
      genes. Maize has numerous BIP-like genes, and ER stress was found to upregulate
      one of these, ZmBIPb. CONCLUSIONS: The splicing of ZmbZIP60 mRNA is an indicator
      of ER stress in maize seedlings resulting from adverse environmental conditions
      such as heat stress. ZmbZIP60 mRNA splicing in maize leads predictively to the
      formation of active bZIP transcription factor targeted to the nucleus to
      upregulate stress response genes. Among the genes upregulated by ER stress in
      maize is one of 22 BIP-like genes, ZmBIPb.

PMID- 22417283
TI  - Structure-activity correlations in a nickel-borate oxygen evolution catalyst.
AB  - An oxygen evolution catalyst that forms as a thin film from Ni(aq)(2+) solutions
      containing borate electrolyte (Ni-B(i)) has been studied by in situ X-ray
      absorption spectroscopy. A dramatic increase in catalytic rate, induced by anodic
      activation of the electrodeposited films, is accompanied by structure and
      oxidation state changes. Coulometric measurements correlated with X-ray
      absorption near-edge structure spectra of the active catalyst show that the
      nickel centers in activated films possess an average oxidation state of +3.6,
      indicating that a substantial proportion of nickel centers exist in a formal
      oxidation state of Ni(IV). In contrast, nickel centers in nonactivated films
      exist predominantly as Ni(III). Extended X-ray absorption fine structure reveals
      that activated catalyst films comprise bis-oxo/hydroxo-bridged nickel centers
      organized into sheets of edge-sharing NiO(6) octahedra. Diminished long-range
      ordering in catalyst films is due to their ostensibly amorphous nature.
      Nonactivated films display a similar oxidic nature but exhibit a distortion in
      the local coordination geometry about nickel centers, characteristic of Jahn
      Teller distorted Ni(III) centers. Our findings indicate that the increase in
      catalytic activity of films is accompanied by changes in oxidation state and
      structure that are reminiscent of those observed for conversion of beta-NiOOH to
      gamma-NiOOH and consequently challenge the long-held notion that the beta-NiOOH
      phase is a more efficient oxygen-evolving catalyst.

PMID- 22417284
TI  - Mental health nurses' views on therapeutic optimism.
AB  - Registered nurses (RN) coordinate acute mental health units on a 24-hour basis
      and it behoves researchers to actually ask these nurses what they think
      contributes to their ability to work with patients in optimistic ways. In this
      study, 40 RN working in acute mental health settings were asked a series of
      questions to explore positive aspects of nursing work, which includes therapeutic
      optimism. Three themes were identified: (i) different ways nurses foster
      therapeutic optimism; (ii) perceptions of how an optimistic environment is
      fostered, and (iii) improvement of ward culture. Findings show the pivotal role
      mental health nurses have in improving teamwork, good communication, sharing, and
      collaboration, in addition to preceptoring and supervision. Furthermore,
      effective clinical management is essential to therapeutic optimism and, in this
      research, is considered to be the aspect of acute mental health nursing most
      relevant to improving the ward culture.

PMID- 22417286
TI  - An analysis of ethical issues in using wastewater analysis to monitor illicit
      drug use.
AB  - AIMS: To discuss ethical issues that may arise in using WWA to monitor illicit
      drug use in the general population and in entertainment precincts, prisons,
      schools and work-places. METHOD: Review current applications of WWA and identify
      ethical and social issues that may be raised with current and projected future
      uses of this method. RESULTS: Wastewater analysis (WWA) of drug residues is a
      promising method of monitoring illicit drug use that may overcome some
      limitations of other monitoring methods. When used for monitoring purposes in
      large populations, WWA does not raise major ethical concerns because individuals
      are not identified and the prospects of harming residents of catchment areas are
      remote. When WWA is used in smaller catchment areas (entertainment venues,
      prisons, schools or work-places) their results could, possibly, indirectly affect
      the occupants adversely. Researchers will need to take care in reporting their
      results to reduce media misreporting. Fears about possible use of WWA for mass
      individual surveillance by drug law enforcement officials are unlikely to be
      realized, but will need to be addressed because they may affect public support
      adversely for this type of research. CONCLUSIONS: Using wastewater analysis to
      monitor illicit drug use in large populations does not raise major ethical
      concerns, but researchers need to minimize possible adverse consequences in
      studying smaller populations, such as workers, prisoners and students.

PMID- 22417285
TI  - The ethylene response factor AtERF98 enhances tolerance to salt through the
      transcriptional activation of ascorbic acid synthesis in Arabidopsis.
AB  - Ascorbic acid (AsA) is an important antioxidant in plants, and its biosynthesis
      is finely regulated through developmental and environmental cues; however, the
      regulatory mechanism remains unclear. In this report, the knockout and knockdown
      mutants of Arabidopsis AtERF98 decreased the AsA level, whereas the
      overexpression of AtERF98 increased it, which suggests that AtERF98 plays an
      important role in regulating AsA biosynthesis. AtERF98-overexpressing plants
      showed enhanced expression of AsA synthesis genes in the d-mannose/l-galactose (d
      Man/l-Gal) pathway and the myo-inositol pathway gene MIOX4, as well as of AsA
      turnover genes. In contrast, AtERF98 mutants showed decreased expression of AsA
      synthesis genes in the d-Man/l-Gal pathway but not of the myo-inositol pathway
      gene or AsA turnover genes. In addition, the role of AtERF98 in regulating AsA
      production was significantly impaired in the d-Man/l-Gal pathway mutant vtc1-1,
      but the expression of the myo-inositol pathway gene or AsA turnover genes was not
      affected, which indicates that the regulation of AtERF98 in AsA synthesis is
      primarily mediated by the d-Man/l-Gal pathway. Transient expression and chromatin
      immunoprecipitation assays further showed that AtERF98 binds to the promoter of
      VTC1, which indicates that AtERF98 modulates AsA biosynthesis by directly
      regulating the expression of the AsA synthesis genes. Moreover, the knockout
      mutant aterf98-1 displayed decreased salt-induced AsA synthesis and reduced
      tolerance to salt. The supplementation of exogenous AsA increased the salt
      tolerance of aterf98-1; coincidently, the enhanced salt tolerance of AtERF98
      overexpressing plants was impaired in vtc1-1. Thus, our data provide evidence
      that the regulation of AtERF98 in AsA biosynthesis contributes to enhanced salt
      tolerance in Arabidopsis.

PMID- 22417287
TI  - Apelin: a peptide involved in cardiovascular risk in hemodialysis patients?
AB  - Inflammation, oxidative stress, and obesity are important features associated
      with pathogenesis of cardiovascular disease, a major contributor to the mortality
      of hemodialysis (HD) patients. Apelin is an adipokine involved in a variety of
      physiological functions; however, little is known about apelin in chronic kidney
      disease (CKD). Thus, the purpose of this study was to analyze apelin plasma
      levels in HD patients and verify whether there is any relationship with
      inflammation, oxidative markers, and obesity. Twenty-four HD patients [53.6 +/-
      14.4 years, 14 men, and body mass index (BMI) of 25.0 +/- 4.2 kg/m(2)] were
      studied and compared with 15 healthy subjects (51.3 +/- 13.5 years, 7 men, and
      BMI of 26.3 +/- 3.7 kg/m(2)). Plasma apelin-12 and -36 were measured using the
      enzyme immunometric assay method. Plasma electronegative low-density lipoprotein
      [LDL(-)] levels were measured using ELISA method, and tumor necrosis factor
      alpha, interleukin-6, leptin, and plasminogen activator inhibitor-1 levels were
      measured by a multiplex assay kit. C-Reactive protein (CRP) was determined by
      immunoturbidimetry. Anthropometric data were also evaluated. There was no
      difference between apelin-36 levels in HD patients (0.82 +/- 0.60 ng/mL) and
      healthy subjects (0.83 +/- 0.23 ng/mL). In contrast, apelin-12 levels were
      significantly higher in patients (0.34 +/- 0.15 ng/mL vs. 0.24 +/- 0.13 ng/mL in
      healthy subjects). TNF-alpha, CRP, and LDL(-) levels were higher in patients;
      however, there was no correlation among apelin-12 or -36 and inflammatory or
      oxidative markers. The adiposity parameters were also not associated with apelin
      12 or -36. In conclusion, plasma apelin seems to be not associated with
      cardiovascular risk in HD patients.

PMID- 22417288
TI  - Molecular and immuno-characteristics of immunoglobulin-like glycoproteins in
      cancer cell-expressed biomarker, CA215.
AB  - RP215 monoclonal antibody (Mab) was shown to recognize a specific carbohydrate
      associated epitope found in cancer cell-expressed glycoproteins, known as CA215.
      The membrane-bound and soluble forms of CA215 were detected in almost all of the
      cancer cells in humans, but rarely found in normal tissues. Through MALDI-TOF MS
      analysis, it has been reported previously that as much as 40% of the detected
      tryptic peptides of CA215 showed high degrees of sequence homology to those found
      in immunoglobulin heavy chains. The cancer cell-derived immunoglobulins were
      further purified from CA215 by affinity column-linked with goat anti-human IgG
      for molecular characterizations. Semi-quantitative RT-PCR was used to determine
      the mRNA levels of various immunoglobulin genes expressed by cancer cells of
      single or multi-cell origins and compared with those found in normal human serum.
      The stability of CA215 was investigated under different experimental conditions.
      It was observed that the RP215-specific epitope in CA215 is stable at neutral pH,
      in human serum or in mice (half life of 5-18 days), but unstable at extreme pH's
      (pH <= 2.0; pH >= 12.0) or high temperatures. Enzyme immunoassays were performed
      with several secondary antibody probes related to human IgG. It was demonstrated
      that cancer cell-expressed immunoglobulins with RP215-specific epitope have much
      lower immunoactivity than that of normal human IgG (<= 5%), despite the fact that
      both showed almost identical amino acid sequence in the respective Fc region
      reported previously. This could be the result of aberrant glycosylation of CA215
      in cancer cells. Aberrant glycosylation of glycoproteins may have important
      biological implications on the proliferation of cancer cells in vitro or in vivo.

PMID- 22417289
TI  - Anticoagulation in cerebral venous sinus thrombosis.

PMID- 22417290
TI  - Beyond semantic accuracy: preschoolers evaluate a speaker's reasons.
AB  - Children's sensitivity to the quality of epistemic reasons and their selective
      trust in the more reasonable of 2 informants was investigated in 2 experiments.
      Three-, 4-, and 5-year-old children (N = 90) were presented with speakers who
      stated different kinds of evidence for what they believed. Experiment 1 showed
      that children of all age groups appropriately judged looking, reliable testimony,
      and inference as better reasons for belief than pretense, guessing, and desiring.
      Experiment 2 showed that 3- and 4-year-old children preferred to seek and accept
      new information from a speaker who was previously judged to use the "best" way of
      thinking. The findings demonstrate that children distinguish certain good from
      bad reasons and prefer to learn from those who showcased good reasoning in the
      past.

PMID- 22417291
TI  - Analysis and design of photobioreactors for microalgae production I: method and
      parameters for radiation field simulation.
AB  - Having capabilities for the simulation of the radiation field in suspensions of
      microalgae constitutes a great asset for the analysis, optimization and scaling
      up of photobioreactors. In this study, a combined experimental and computational
      procedure is presented, specifically devised for the assessment of the
      coefficients of absorption and scattering, needed for the simulation of such
      fields. The experimental procedure consists in measuring the radiant energy
      transmitted through samples of suspensions of microalgae of different biomass
      concentrations, as well as the forward and backward scattered light. At a
      microscopic level, suspensions of microalgae are complex heterogeneous media and
      due to this complexity, in this study they are modeled as a pseudocontinuum, with
      centers of absorption and scattering randomly distributed throughout its volume.
      This model was tested on suspensions of two algal species of dissimilar cell
      shapes: Chlorella sp. and Scenedesmus quadricauda. The Monte Carlo simulation
      algorithm developed in this study, when used as a supporting subroutine of a main
      optimization program based on a genetic algorithm, permits the assessment of the
      physical parameters of the radiation field model. The Monte Carlo algorithm
      simulates the experiments, reproducing the events that photons can undergo while
      they propagate through culture samples or at its physical boundaries.

PMID- 22417292
TI  - First case of Aeromonas schubertii infection in the freshwater cultured snakehead
      fish, Ophiocephalus argus (Cantor), in China.
AB  - An epizootic in snakehead fish, Ophiocephalus argus, in earthen ponds in
      Xianning, Hubei Province, central China, from June to August 2009 was found to be
      caused by Aeromonas schubertii. The cumulative mortality within 40 days was 45%,
      and the diseased fish were 18 months old and 35-45 cm in length. Multiple, ivory
      white, firm nodules, 0.5-1 mm in diameter, were scattered throughout the kidney.
      Blood clots, 3-5 mm in diameter, were found in the liver. This is a disease
      frequently found in cultured snakehead throughout China. Isolated bacteria were
      Gram negative, facultatively anaerobic, motile, short rod-shaped, with a length
      of 0.3-1.0 MUm. Morphological and biochemical tests, as well as phylogenetic
      analysis derived from 16S rRNA, gyrB, rpoD and dnaJ gene sequencing all strongly
      indicated that these snakehead isolates are identical to A. schubertii. In
      addition, the isolates possessed two plasmids: 5.0 kb and 10.0 kb. Antibiotic
      sensitivity testing of the isolates was carried out by the standard Kirby-Bauer
      disc diffusion method. Experimental infection assays were conducted, and
      pathogenicity (by intraperitoneal injection) was demonstrated in snakehead
      fingerlings and zebrafish, Brachydanio rerio (Hamilton).

PMID- 22417293
TI  - Dynamic kinetic resolution of 1,3-dihydro-2H-isoindole-1-carboxylic acid methyl
      ester: asymmetric transformations toward isoindoline carbamates.
AB  - Asymmetric syntheses of isoindoline carbamates have been successfully achieved
      through enzyme-mediated dynamic kinetic resolution processes and without
      requirement of metal or acid-base catalyst for the substrate racemization.
      Optically active carbamates were obtained in good yields and an excellent degree
      of stereoselectivity when  Pseudomonas cepacia  lipase (PSL) was used as
      biocatalyst, with diallyl or dibenzyl carbonates being both adequate reagents in
      alkoxycarbonylation reactions.

PMID- 22417294
TI  - Pyrosequencing reveals unique microbial signatures associated with healthy and
      failing dental implants.
AB  - AIM: Although it is established that peri-implantitis is a bacterially induced
      disease, little is known about the bacterial profile of peri-implant communities
      in health and disease. The purpose of the present investigation was to examine
      the microbial signatures of the peri-implant microbiome in health and disease.
      MATERIALS AND METHODS: Subgingival and submucosal plaque samples were collected
      from forty subjects with periodontitis, peri-implantitis, periodontal and peri
      implant health and analysed using 16S pyrosequencing. RESULTS: Peri-implant
      biofilms demonstrated significantly lower diversity than subgingival biofilms in
      both health and disease, however, several species, including previously
      unsuspected and unknown organisms, were unique to this niche. The predominant
      species in peri-implant communities belonged to the genera Butyrivibrio,
      Campylobacter, Eubacterium, Prevotella, Selenomonas, Streptococcus, Actinomyces,
      Leptotrichia, Propionibacterium, Peptococcus, Lactococcus and Treponema. Peri
      implant disease was associated with lower levels of Prevotella and Leptotrichia
      and higher levels of Actinomyces, Peptococcus, Campylobacter, non-mutans
      Streptococcus, Butyrivibrio and Streptococcus mutans than healthy implants. These
      communities also demonstrated lower levels of Prevotella, non-mutans
      Streptococcus, Lactobacillus, Selenomonas, Leptotrichia, Actinomyces and higher
      levels of Peptococcus, Mycoplasma, Eubacterium, Campylobacter, Butyrivibrio, S.
      mutans and Treponema when compared to periodontitis-associated biofilms.
      CONCLUSION: The peri-implant microbiome differs significantly from the
      periodontal community in both health and disease. Peri-implantitis is a
      microbially heterogeneous infection with predominantly gram-negative species, and
      is less complex than periodontitis.

PMID- 22417295
TI  - Costs of paediatric diabetes care in Germany: current situation and comparison
      with the year 2000.
AB  - AIMS: To estimate direct costs of paediatric Type 1 diabetes care and associated
      factors in Germany for the year 2007 and to compare results with the costs for
      the year 2000. METHODS: Our study includes clinical data and charges for any
      diabetes-related health care service of 14,185 continually treated subjects with
      paediatric diabetes aged < 20 years [52.5% male, mean age (SD) 12.1 (4.2) years],
      derived from a nationwide prospective patient documentation system (DPV). Health
      care utilization was valued in monetary terms by using inpatient and outpatient
      medical fees and retail prices (perspective of the statutory health insurance).
      Associations between average total diabetes-related costs or various single cost
      categories per patient and age, sex, migration background, diabetes duration, and
      metabolic control were analysed by multiple regression procedures and by a two
      part model for hospitalization costs. Total direct costs in the whole paediatric
      diabetes population in Germany were estimated. Mean costs per patient as well as
      total costs in the German paediatric diabetes population in 2007 were compared to
      2000 costs (inflated to the year 2007). RESULTS: Mean direct diabetes-associated
      costs per subject were ?3524 (inter-quartile range: 1831-4743). Main cost
      categories were hospitalization (32%), glucose self-monitoring (29%), insulin
      pump therapy (18%), and insulin (15%). Based on the present estimation, the total
      costs of paediatric diabetes care in Germany exceeded ?110 million in 2007.
      Compared with estimates of the year 2000, average costs per patient had increased
      by 20% and total costs for German paediatric diabetes care by 47%. CONCLUSIONS:
      Direct costs for paediatric Type 1 diabetes care increased between 2000 and 2007,
      probably partly because of new therapeutic strategies and an increase in diabetes
      prevalence.

PMID- 22417296
TI  - Stem cells in asexual reproduction of Enchytraeus japonensis (Oligochaeta,
      Annelid): proliferation and migration of neoblasts.
AB  - Enchytraeus japonensis is a small oligochaete that reproduces mainly asexually by
      fragmentation (autotomy) and regeneration. As sexual reproduction can also be
      induced, it is a good animal model for the study of both somatic and germline
      stem cells. To clarify the features of stem cells in regeneration, we
      investigated the proliferation and lineage of stem cells in E. japonensis.
      Neoblasts, which have the morphological characteristics of undifferentiated
      cells, were found to firmly adhere to the posterior surface of septa in each
      trunk segment. Also, smaller neoblast-like cells, which are designated as N-cells
      in this study, were located dorsal to the neoblasts on the septa. By conducting 5
      bromo-2'-deoxyuridine (BrdU)-labeling-experiments, we have shown that neoblasts
      are slow-cycling (or quiescent) in intact growing worms, but proliferate rapidly
      in response to fragmentation. N-cells proliferate more actively than do neoblasts
      in intact worms. The results of pulse-chase experiments indicated that neoblast
      and N-cell lineage mesodermal cells that incorporated BrdU early in regeneration
      migrated toward the autotomized site to form the mesodermal region of the
      blastema, while the epidermal and intestinal cells also contributed to the
      blastema locally near the autotomized site. We have also shown that neoblasts
      have stem cell characteristics by expressing Ej-vlg2 and by the activity of
      telomerase during regeneration. Telomerase activity was high in the early stage
      of regeneration and correlated with the proliferation activity in the neoblast
      lineage of mesodermal stem cells. Taken together, our results indicate that
      neoblasts are mesodermal stem cells involved in the regeneration of E.
      japonensis.

PMID- 22417297
TI  - Thrombolytic therapy and outcome of patients with an acute symptomatic pulmonary
      embolism.
AB  - BACKGROUND: While the primary therapy for most patients with a pulmonary embolism
      (PE) consists of anticoagulation, the efficacy of thrombolysis relative to
      standard therapy remains unclear. METHODS: In this retrospective cohort study of
      15,944 patients with an objectively confirmed symptomatic acute PE, identified
      from the multicenter, international, prospective, Registro Informatizado de la
      Enfermedad TromboEmbolica (RIETE registry), we aimed to assess the association
      between thrombolytic therapy and all-cause mortality during the first 3 months
      after the diagnosis of a PE. After creating two subgroups, stratified by systolic
      blood pressure (SBP) (< 100 mm Hg vs. other), we used propensity score-matching
      for a comparison of patients who received thrombolysis to those who did not in
      each subgroup. RESULTS: Patients who received thrombolysis were younger, had
      fewer comorbid diseases and more signs of clinical severity compared with those
      who did not receive it. In the subgroup with systolic hypotension, analysis of
      propensity score-matched pairs (n = 94 pairs) showed a non-statistically
      significant but clinically relevant lower risk of death for thrombolysis compared
      with no thrombolysis (odds ratio [OR] 0.72; 95% confidence interval [CI], 0.36
      1.46; P = 0.37). In the normotensive subgroup, analysis of propensity score
      matched pairs (n = 217 pairs) showed a statistically significant and clinically
      meaningful increased risk of death for thrombolysis compared with no thrombolysis
      (OR 2.32; 95% CI, 1.15-4.68; P = 0.018). When we imputed data for missing values
      for echocardiography and troponin tests in the group of normotensive patients, we
      no longer detected the increased risk of death associated with thrombolytic
      therapy. CONCLUSIONS: In normotensive patients with acute symptomatic PE,
      thrombolytic therapy is associated with a higher risk of death than no
      thrombolytic therapy. In hemodynamically unstable patients, thrombolytic therapy
      is possibly associated with a lower risk of death than no thrombolytic therapy.
      However, study design limitations do not imply a causal relationship between
      thrombolytics and outcome.

PMID- 22417298
TI  - Cutoffs and k-mers: implications from a transcriptome study in allopolyploid
      plants.
AB  - BACKGROUND: Transcriptome analysis is increasingly being used to study the
      evolutionary origins and ecology of non-model plants. One issue for both
      transcriptome assembly and differential gene expression analyses is the common
      occurrence in plants of hybridisation and whole genome duplication (WGD) and
      hybridization resulting in allopolyploidy. The divergence of duplicated genes
      following WGD creates near identical homeologues that can be problematic for de
      novo assembly and also reference based assembly protocols that use short reads
      (35 - 100 bp). RESULTS: Here we report a successful strategy for the assembly of
      two transcriptomes made using 75 bp Illumina reads from Pachycladon fastigiatum
      and Pachycladon cheesemanii. Both are allopolyploid plant species (2n = 20) that
      originated in the New Zealand Alps about 0.8 million years ago. In a systematic
      analysis of 19 different coverage cutoffs and 20 different k-mer sizes we showed
      that i) none of the genes could be assembled across all of the parameter space
      ii) assembly of each gene required an optimal set of parameter values and iii)
      these parameter values could be explained in part by different gene expression
      levels and different degrees of similarity between genes. CONCLUSIONS: To obtain
      optimal transcriptome assemblies for allopolyploid plants, k-mer size and k-mer
      coverage need to be considered simultaneously across a broad parameter space.
      This is important for assembling a maximum number of full length ESTs and for
      avoiding chimeric assemblies of homeologous and paralogous gene copies.

PMID- 22417300
TI  - Interfollicular epidermal homeostasis: dicing with differentiation.
AB  - In the 1970s, studies of tissue architecture and cell proliferation were used to
      formulate a new model of epidermal homeostasis. This asserted that the tissue was
      maintained by long-lived, slow-cycling, self-renewing stem cells that generate a
      short-lived population of transit amplifying (TA) cells, which undergo terminal
      differentiation after a set number of cell divisions. It was further hypothesized
      that in the epidermis, the tissue was organized into clonal epidermal
      proliferative units (EPUs) comprising a central stem cell with surrounding TA
      cells, which maintain the overlying differentiated cell layers. The stem/TA and
      EPU hypotheses have been widely influential. Here, we first revaluate older
      literature, finding numerous studies that conflict with the EPU model. We then
      review recent large-scale lineage tracing studies in transgenic mice which
      exclude the stem/TA and EPU hypotheses, and reveal that the epidermis is
      maintained by a single population of functionally equivalent cycling progenitor
      cells. The outcome of individual progenitor cell divisions is random, but the
      probabilities of generating differentiated and progenitor cell daughters are
      equal, so that homeostasis is maintained across the progenitor population. We
      reconcile this model with the older literature and place the epidermis in the
      context of other tissues that are also maintained by continually cycling cells
      with stochastic fate.

PMID- 22417299
TI  - Recent updates on the role of microRNAs in prostate cancer.
AB  - MicroRNAs (miRNAs) are short non-coding RNAs that are involved in several
      important biological processes through regulation of genes post
      transcriptionally. Carcinogenesis is one of the key biological processes where
      miRNAs play important role in the regulation of genes. The miRNAs elicit their
      effects by binding to the 3' untranslated region (3'UTR) of their target mRNAs,
      leading to the inhibition of translation or the degradation of the mRNA,
      depending on the degree of complementary base pairing. To-date more than 1,000
      miRNAs are postulated to exist, although the field is moving rapidly. Currently,
      miRNAs are becoming the center of interest in a number of research areas,
      particularly in oncology, as documented by exponential growth in publications in
      the last decade. These studies have shown that miRNAs are deregulated in a wide
      variety of human cancers. Thus, it is reasonable to ask the question whether
      further understanding on the role of miRNAs could be useful for diagnosis,
      prognosis and predicting therapeutic response for prostate cancer (PCa).
      Therefore, in this review article, we will discuss the potential roles of
      different miRNAs in PCa in order to provide up-to-date information, which is
      expected to stimulate further research in the field for realizing the benefit of
      miRNA-targeted therapeutic approach for the treatment of metastatic castrate
      resistant prostate cancer (mCRPC) in the near future because there is no curative
      treatment for mCRPC at the moment.

PMID- 22417301
TI  - MAPK and PI3K/AKT mediated YB-1 activation promotes melanoma cell proliferation
      which is counteracted by an autoregulatory loop.
AB  - Y-box binding protein 1 (YB-1) is an oncogenic transcription and translation
      factor and is overexpressed in several types of cancer. Our previous data showed
      that YB-1 is upregulated and translocated to the nucleus during melanoma
      progression and that YB-1 is an important transcription factor regulating
      proliferation, survival, migration, invasion and chemosensitivity of melanoma
      cells. It has been suggested that YB-1 is activated and translocated to the
      nucleus after S102-phosphorylation in the DNA binding domain. In this study, we
      show that activation of YB-1 by S102-phosphorylation and nuclear translocation is
      increased during melanoma progression using a human tissue microarray with 100
      melanocytic lesions. Furthermore, we analysed the mechanisms governing the
      expression and activity of YB-1 in melanoma cells. We show that the PI3K/AKT and
      p53 signalling, growth factors and chemotherapeutic agents increase YB-1 promoter
      activity. This, however, resulted in no or only modest increase in YB-1 protein
      expression. We show that the MAPK and PI3K/AKT signalling pathways, both
      activated in melanoma cells, as well as p53 overexpression increase YB-1 S102
      phosphorylation, whereas NFkappaB signalling inhibits phosphorylation.
      Overexpression of YB-1 in melanoma cells inhibits translation efficiency and by
      this proliferation and survival of melanoma cells indicating that there is an
      autoregulatory loop restricting YB-1 protein expression. These data suggest that
      there is a tightly regulated feedback mechanism regulating YB-1 expression and
      activation, necessary for proper cell cycle progression of melanoma cells.

PMID- 22417302
TI  - Murine filaggrin-2 is involved in epithelial barrier function and down-regulated
      in metabolically induced skin barrier dysfunction.
AB  - The S100 fused-type proteins (SFTPs) are thought to be involved in the barrier
      formation and function of the skin. Mutations in the profilaggrin gene, one of
      the best investigated members of this family, are known to be the major risk
      factors for ichthyosis vulgaris and atopic dermatitis. Recently, we identified
      human filaggrin-2 as a new member of the SFTP family. To achieve further insight
      into its function, here the murine filaggrin-2 was analysed as a possible
      orthologue. The 5' and 3' ends of the mouse filaggrin-2 cDNA of the BALB/c strain
      were sequenced and confirmed an organization typical for SFTPs. Murine filaggrin
      2 showed an expression pattern mainly in keratinizing epithelia in the upper cell
      layers on both mRNA and protein levels. The expression in cultured mouse
      keratinocytes was increased upon elevated Ca(2+)  levels. Immunoblotting
      experiments indicated an intraepidermal processing of the 250-kDa full-length
      protein. In metabolically (essential fatty acid-deficient diet) induced skin
      barrier dysfunction, filaggrin-2 expression was significantly reduced, whereas
      filaggrin expression was up-regulated. In contrast, mechanical barrier disruption
      with acetone treatment did not affect filaggrin-2 mRNA expression. These results
      suggest that filaggrin-2 may contribute to epidermal barrier function and its
      regulation differs, at least in parts, from that of filaggrin.

PMID- 22417303
TI  - Infrequent p53 gene mutation but UV gradient-like p53 protein positivity in
      keloids.
AB  - Keloids are characterized by extreme fibroblastic overgrowth of unknown
      pathogenesis after skin injury. Previous studies, mostly in non-Caucasian
      populations, suggest that p53 mutations may be involved. To substantiate this, we
      performed DNA sequence analysis of exons 4-8 of the p53 gene and
      immunohistochemical staining of p53 protein in archived keloidal tissue samples
      from 23 Caucasian patients. In contrast to previous reports, we found mutated p53
      in keloidal tissue in a minority of cases (2/23; 12%). The G allele frequency and
      C allele frequency at the p53 polymorphic codon 72 were 0.72 (33/46) and 0.28
      (13/46), respectively, in our study, a finding that was similar to the 0.77
      (184/240) vs. 0.23 (56/240) (P = 0.4580; chi-squared test) observed in the Hap
      Map data of a European population but statistically significantly different from
      the 0.43 (547/1258) vs. 0.57 (711/1258) (P = 0.0002; chi-squared test) observed
      in the 1000 Genome project [Database of Single Nucleotide Polymorphisms (dbSNP).
      Bethesda (MD): National Center for Biotechnology Information, National Library of
      Medicine. dbSNP accession:rs1042522, (dbSNP Build ID: 132). Available from:
      (http://www.ncbi.nlm.nih.gov/SNP/] a difference most likely due to the different
      genetic background of the populations enrolled. However, one-third of the
      keloidal samples showed lesional nuclear p53 staining with a UV penetration
      gradient-like positivity (P <= 0.0084). Staining with an anti-cyclobutane
      pyrimidine dimer antibody revealed the total absence of short-term photoproducts
      in the epidermis as well as keloidal tissue. Furthermore, all fibroblasts
      expressing p53 stained negative for Ki-67, indicating that these cells were in a
      quiescent stage and p53 upregulation did not contribute to keloidal
      proliferation. We conclude that p53 plays no major role in the pathogenesis of
      keloids in the Caucasian population.

PMID- 22417304
TI  - In vivo quantification of epidermis pigmentation and dermis papilla density with
      reflectance confocal microscopy: variations with age and skin phototype.
AB  - Reflectance confocal microscopy (RCM) may help to quantify variations of skin
      pigmentation induced by different stimuli such as UV radiation or therapeutic
      intervention. The objective of our work was to identify RCM parameters able to
      quantify in vivo dermis papilla density and epidermis pigmentation potentially
      applicable in clinical studies. The study included 111 healthy female volunteers
      with phototypes I-VI. Photo-exposed and photo-protected anatomical sites were
      imaged. The effect of age was also assessed. Four epidermis components were
      specifically investigated: stratum corneum, stratum spinosum, basal epidermal
      layer and dermo-epidermal junction. Laser power, diameter of corneocytes and
      upper spinous keratinocytes, brightness of upper spinous and interpapillary
      spinous keratinocytes, number of dermal papillae and papillary contrast were
      systematically assessed. Papillary contrast measured at the dermo-epidermal
      junction appeared to be a reliable marker of epidermis pigmentation and showed a
      strong correlation with skin pigmentation assessed clinically using the
      Fitzpatrick's classification. Brightness of upper spinous and interpapillary
      spinous keratinocytes was not influenced by the skin phototype. The number of
      dermal papillae was significantly lower in subjects with phototypes I-II as
      compared with darker skin subjects. A dramatic reduction in the number of dermal
      papillae was noticed with age, particularly in subjects with fair skin. The
      method presented here provides a new in vivo investigation tool for
      quantification of dermis papilla density and epidermal pigmentation. Papillary
      contrast measured at the dermo-epidermal junction may be selected as a marker of
      skin pigmentation for evaluation in clinical studies.

PMID- 22417305
TI  - Resistance of Sezary cells to TNF-alpha-induced apoptosis is mediated in part by
      a loss of TNFR1 and a high level of the IER3 expression.
AB  - Failure to execute an apoptotic programme is one of the critical steps and a
      common mechanism promoting tumorogenesis. Immediate early responsive gene 3
      (IER3) has been shown to be upregulated in several cancers. IER3 is a stress
      induced gene, which upregulation leads to reduction in production of reactive
      oxygen species (ROS) protecting malignant cells from apoptosis. We observed that
      malignant lymphocytes from patients with Sezary syndrome (SzS) were resistant to
      pro-apoptotic dose of tumour necrosis factor-alpha (TNF-alpha). The aim of this
      study was to investigate the role of IER3 in the mechanism of such resistance.
      CD4+ CD26- lymphocytes from the peripheral blood of patients with SzS and healthy
      controls were negatively selected using CD4 and CD26 magnetic beads and analysed
      for expression of TNFR1, TNFR2, IER3 expression, and ROS production in response
      to TNF-alpha at an apoptotic dose. Sezary cells with a higher level of IER3
      expression retained their viability to TNF-alpha. IER3 upregulation correlated
      with a decrease level of intracellular ROS and low TNFR1 expression on malignant
      cells. Targeting IER3 could be of interest for the development of future
      therapeutic strategies for patients with SzS.

PMID- 22417306
TI  - An ErbB receptor-mediated AP-1 regulatory network is modulated by STAT3 and c-MYC
      during calcium-dependent keratinocyte differentiation.
AB  - A calcium gradient in skin epidermis is known to regulate epidermal
      differentiation. In cultures of human epidermal keratinocytes (NHEK), induction
      of calcium-dependent differentiation is associated with phosphorylation of ErbB
      receptors, including the epidermal growth factor receptor (EGFR). The activation
      of EGFR triggers the induction of activator protein 1 (AP-1) proteins necessary
      for keratinocyte terminal differentiation. Interestingly, an in vitro long-term
      calcium treatment revealed the activation of different ErbB receptors with
      different timings, which is consistent with the differential localization of each
      receptor in the skin layers in vivo. In the current study, the regulatory
      relationship between ErbB receptor activation and induction of AP-1 proteins in
      calcium-dependent keratinocyte differentiation was analysed. For this purpose, we
      used a mathematical method to predict molecular regulations from time-course
      proteomic data of 30 target components. The predicted network showed that the
      ErbB receptor might regulate AP-1 protein expression via two pathways: positive
      regulation by c-MYC and negative regulation by signal transducer and activator of
      transcription 3 (STAT3) pathways. Experimental validation analysis revealed that
      ErbB receptor inhibition resulted in defective induction of AP-1 proteins and
      suppressed terminal differentiation of keratinocytes. Inhibition of STAT3,
      however, affected expression of a partial set of AP-1 proteins and resulted in
      premature differentiation. Studies using RNAi to diminish expression of each ErbB
      receptor and the AP-1 proteins strongly suggested that STAT3 established a
      balance that maintains the appropriate set of AP-1 proteins and participates in a
      complex network for regulating keratinocyte differentiation.

PMID- 22417307
TI  - Comparison of microRNA expression using different preservation methods of matched
      psoriatic skin samples.
AB  - MicroRNAs are non-coding RNA molecules modulating gene expression post
      transcriptionally. Formalin-fixed, paraffin-embedding (FFPE) is a standard
      preservation method often used in clinical practices, but induces RNA
      degradation. Extracting high-quality RNA from human skin can be challenging as
      skin contains high levels of RNases. As microRNAs are 19-23 nucleotides long and
      lack a poly-A tail, they may be less prone to RNA degradation than mRNAs. We
      investigated whether microRNAs in psoriatic (FFPE) samples reliably reflect
      microRNA expression in samples less prone to RNA degradation such as fresh-frozen
      (FS) and Tissue-Tek-embedding (OCT). We found a strong correlation of the
      microRNA expression levels between all preservation methods of matched psoriatic
      skin samples (r(s) ranging from 0.91 to 0.95 (P < 0.001)). These observations
      were further confirmed with qRT-PCR. Our results demonstrate that microRNA
      detection in human skin is robust irrespective of preservation method; thus,
      microRNAs offer an appropriate and flexible approach in clinical practices and
      for diagnostic purposes in skin disorders.

PMID- 22417308
TI  - Xeroderma pigmentosum complementation group G patient with a novel homozygous
      missense mutation and no neurological abnormalities.
AB  - We describe an unusual xeroderma pigmentosum (XP) patient with a mutation in XP
      complementation group G, representing only the third reported Japanese XP-G
      patient. A 40-year-old men (XP3HM), born from consanguineous parents experienced
      sun sensitivity and pigmentary changes of sun-exposed skin since childhood. He
      developed a squamous cell carcinoma on his lower lip at the age of 40. He has
      neither neurological abnormalities nor Cockayne syndrome. The primary fibroblasts
      of the patient were hypersensitive to killing by UV (D(0) = 0.6 J/m(2)) and the
      post-UV unscheduled DNA synthesis was 8% of normal. Host cell reactivation
      complementation analysis implicated XP complementation group G. We identified a
      novel homozygous mutation (c.194T>C) in a conserved portion of the XPG(ERCC5)
      gene, resulting in a predicted amino acid change; p.L65P. We confirmed that this
      genetic change reduced DNA repair thus linking this mutation to increased skin
      cancer.

PMID- 22417309
TI  - Hair-inducing ability of human dermal papilla cells cultured under Wnt/beta
      catenin signalling activation.
AB  - It is well known that dermal papilla cells (DPCs) play crucial roles in hair
      follicle induction. In this study, we examined whether Wnt/beta-catenin
      activation results in maintenance of the hair-inducing ability of human DPCs.
      Expression of DPC marker genes was maintained under Wnt/beta-catenin signalling
      stimulation by GSK-3beta inhibition. Furthermore, human DPCs showed constant hair
      induction when transplanted with murine epidermal cell fraction. Alu-positive
      human DPCs were essentially detected adjacent to the reconstructing epidermal
      structure positive for P-cadherin immunoreactivity. The transplanted human DPCs
      were abundant in the surrounding dermal sheath portion of the fully regenerated
      hair follicles. These results support the importance of Wnt/beta-catenin
      signalling in hair follicle induction. This study may provide valuable
      information to establish a culture method of human DPCs for cell-based therapy.

PMID- 22417310
TI  - Vaspin--a link of obesity and psoriasis?
AB  - Psoriasis is an inflammatory skin disease often associated with obesity. The anti
      inflammatory adipokine vaspin, a suggested serine proteinase inhibitor of the
      serpin family, is discussed as a new link between inflammation and obesity. Here,
      we demonstrate that - different from healthy controls - vaspin serum levels in
      patients with psoriasis were body mass index independent. Moreover, we could
      identify keratinocytes as the major source of vaspin in skin. Vaspin expression
      in lesional psoriatic skin was reduced compared with uninvolved skin as shown by
      immunohistochemistry and RT-PCR. In aggregate, we report on the cellular source
      of vaspin in skin and its expression in psoriasis.

PMID- 22417311
TI  - MiR-21 is up-regulated in psoriasis and suppresses T cell apoptosis.
AB  - MicroRNAs are short non-coding RNAs that regulate gene expression. Previously, in
      a genome-wide screen, we found deregulation of microRNA expression in psoriasis
      skin. MicroRNA-21 (miR-21) is one of the microRNAs significantly up-regulated in
      psoriasis skin lesions. To identify the cell type responsible for the increased
      miR-21 level, we compared expression of miR-21 in epidermal cells and dermal T
      cells between psoriasis and healthy skin and found elevated levels of miR-21 in
      psoriasis in both cell types. In cultured T cells, expression of miR-21 increased
      markedly upon activation. To explore the function of miR-21 in primary human T
      helper cells, we inhibited miR-21 using a tiny seed-targeting LNA-anti-miR.
      Specific inhibition of miR-21 increased the apoptosis rate of activated T cells.
      Our results suggest that miR-21 suppresses apoptosis in activated T cells, and
      thus, overexpression of miR-21 may contribute to T cell-derived psoriatic skin
      inflammation.

PMID- 22417312
TI  - Immortalized sebocytes can spontaneously differentiate into a sebaceous-like
      phenotype when cultured as a 3D epithelium.
AB  - Sebocytes originate from the same lineage as keratinocytes, and both cell types
      may have similarities in terms of growth and differentiation. We were interested
      in studying the behaviour of human sebocytes when cultured in conditions
      validated for epidermal reconstruction. For this purpose, we established a HPV16
      E6/7-immortalized human sebocyte cell line (SEBO662) growing in keratinocyte
      defined media. Postconfluent SEBO662 cells in monolayers express the early
      sebocyte marker, cytokeratin 7 (K7), do not express Epithelia Membrane Antigen
      (EMA) and do not exhibit strong lipogenic activity. However, when placed at the
      air-liquid interface, SEBO662 multilayers spontaneously differentiate into a
      sebaceous-like structure as shown by the strong polarized expression of the late
      sebaceous marker EMA, the overexpression of some lipogenic markers and lipid
      production on the upper side of the epithelium. This work highlights the value of
      simple 3D models for exhibiting spontaneous differentiation and polarization.

PMID- 22417313
TI  - Characterization of the miRNA profile in UVB-irradiated normal human
      keratinocytes.
AB  - The aim of this study was to assess the effects of ultraviolet B (UVB)
      irradiation on microRNA (miRNA) expression in normal human keratinocytes. Global
      miRNA expression profiles of primary cultures of normal human keratinocytes 4 and
      24 h postirradiation were studied using miRNA microarray with further
      confirmation by real-time PCR. We found that upon 30 or 60 mJ/cm(2) of UVB
      radiation, the expression of 44 miRNAs was up- or downregulated more than twofold
      compared with non-irradiated keratinocytes. MiRNAs were either up- or
      downregulated after 4 h and then either returned to normal levels or remained
      affected after 24 h, resulting in four distinct patterns of miRNA expression
      change. It appears that acute exposure of keratinocytes to UVB radiation results
      in several specific patterns of miRNA response.

PMID- 22417314
TI  - Impacts of rising health care costs on families with employment-based private
      insurance: a national analysis with state fixed effects.
AB  - BACKGROUND: Given the rapid growth of health care costs, some experts were
      concerned with erosion of employment-based private insurance (EBPI). This
      empirical analysis aims to quantify the concern. METHODS: Using the National
      Health Account, we generated a cost index to represent state-level annual cost
      growth. We merged it with the 1996-2003 Medical Expenditure Panel Survey. The
      unit of analysis is the family. We conducted both bivariate and multivariate
      logistic analyses. RESULTS: The bivariate analysis found a significant inverse
      association between the cost index and the proportion of families receiving an
      offer of EBPI. The multivariate analysis showed that the cost index was
      significantly negatively associated with the likelihood of receiving an EBPI
      offer for the entire sample and for families in the first, second, and third
      quartiles of income distribution. The cost index was also significantly
      negatively associated with the proportion of families with EBPI for the entire
      year for each family member (EBPI-EYEM). The multivariate analysis confirmed
      significance of the relationship for the entire sample, and for families in the
      second and third quartiles of income distribution. Among the families with EBPI
      EYEM, there was a positive relationship between the cost index and this group's
      likelihood of having out-of-pocket expenditures exceeding 10 percent of family
      income. The multivariate analysis confirmed significance of the relationship for
      the entire group and for families in the second and third quartiles of income
      distribution. CONCLUSIONS: Rising health costs reduce EBPI availability and
      enrollment, and the financial protection provided by it, especially for middle
      class families.

PMID- 22417315
TI  - Endocytotic uptake of nutrients in carnivorous plants.
AB  - Carnivorous plants trap, digest and absorb animals in order to supplement their
      mineral nutrition. Nutrients absorbed by the plant include different nitrogen
      species, phosphate, potassium, trace elements and small organic compounds. Uptake
      is usually thought to be performed via specific channels, but this study provides
      evidence that endocytosis is involved as well. Traps of the carnivorous plants
      Nepenthes coccinea, Nepenthes ventrata, Cephalotus follicularis, Drosophyllum
      lusitanicum, Drosera capensis, Dionaea muscipula, Aldrovanda vesiculosa, Genlisea
      violacea * lobata, Sarracenia psittacina and Sarracenia purpurea were stained
      with methylene blue in order to identify possible sites of uptake. The permeable
      parts of the traps were incubated with fluorescein isothiocyanate labelled bovine
      serum albumin (FITC-BSA) and other fluorescent endocytosis markers, combined with
      the soluble protein BSA or respiratory inhibitors. Uptake was studied by confocal
      microscopy. In Nepenthes, small fluorescent vesicles became visible 1 h after
      incubation with FITC-BSA. These vesicles fused to larger compartments within 30
      h. A similar behaviour was found in the related genera Drosera, Dionaea,
      Aldrovanda and Drosophyllum but also in Cephalotus with glands of different
      evolutionary origin. In Genlisea and Sarracenia, no evidence for endocytosis was
      found. We propose that in many carnivorous plants, nutrient uptake by carriers is
      supplemented by endocytosis, which enables absorption and intracellular digestion
      of whole proteins. The advantage for the plant of reducing secretion of enzymes
      for extracellular digestion is evident.

PMID- 22417317
TI  - Effect of poly-beta-hydroxybutyrate on Chinese mitten crab, Eriocheir sinensis,
      larvae challenged with pathogenic Vibrio anguillarum.
AB  - This study investigated the protective effect of poly-beta-hydroxybutyrate (PHB)
      on Chinese mitten crab, Eriocheir sinensis, zoea larvae challenged with
      pathogenic Vibrio anguillarum. PHB was delivered to the crab larvae through
      rotifer and Artemia bioencapsulation. Zoea 3 larvae were challenged with V.
      anguillarum at a final concentration of 10(5) CFU mL(-1). PHB-enriched rotifers
      and Artemia nauplii were added to the culture water 24 h prior to, upon and 24 h
      after challenge. The results confirmed that PHB could enhance the survival and
      growth of unexposed E. sinensis larvae. Moreover, PHB protected larvae from the
      pathogen as the larvae fed PHB-enriched live food showed the highest survival and
      development rate in all challenged groups (P < 0.05). Furthermore, larval
      performance was the best when PHB was delivered to the larvae 24 h before
      challenge (P < 0.05). In conclusion, our results indicate that PHB can be used as
      part of an effective strategy to protect E. sinensis larvae from V. anguillarum
      resulting in higher survival and better growth, especially when applied before
      the challenge.

PMID- 22417316
TI  - Randomized trial of Tapas Acupressure Technique for weight loss maintenance.
AB  - BACKGROUND: Obesity is an urgent public health problem, yet only a few clinical
      trials have systematically tested the efficacy of long-term weight-loss
      maintenance interventions. This randomized clinical trial tested the efficacy of
      a novel mind and body technique for weight-loss maintenance. METHODS:
      Participants were obese adults who had completed a six-month behavioral weight
      loss program prior to randomization. Those who successfully lost weight were
      randomized into either an experimental weight-loss maintenance intervention,
      Tapas Acupressure Technique (TAT(r)), or a control intervention comprised of
      social-support group meetings (SS) led by professional facilitators. TAT combines
      self-applied light pressure to specific acupressure points accompanied by a
      prescribed sequence of mental steps. Participants in both maintenance conditions
      attended eight group sessions over six months of active weight loss maintenance
      intervention, followed by an additional 6 months of no intervention. The main
      outcome measure was change in weight from the beginning of the weight loss
      maintenance intervention to 12 months later. Secondary outcomes were change in
      depression, stress, insomnia, and quality of life. We used analysis of covariance
      as the primary analysis method. Missing values were replaced using multiple
      imputation. RESULTS: Among 285 randomized participants, 79% were female, mean age
      was 56 (standard deviation (sd) = 11), mean BMI at randomization was 34 (sd = 5),
      and mean initial weight loss was 9.8 kg (sd = 5). In the primary outcome model,
      there was no significant difference in weight regain between the two arms (1.72
      kg (se 0.85) weight regain for TAT and 2.96 kg (se 0.96) weight regain for SS, p
      < 0.097) Tests of between- arm differences for secondary outcomes were also not
      significant. A secondary analysis showed a significant interaction between
      treatment and initial weight loss (p < .036), with exploratory post hoc tests
      showing that greater initial weight loss was associated with more weight regain
      for SS but less weight regain for TAT. CONCLUSIONS: The primary analysis showed
      no significant difference in weight regain between TAT and SS, while secondary
      and post hoc analyses indicate direction for future research.

PMID- 22417318
TI  - The coexistence of natural and supernatural explanations across cultures and
      development.
AB  - Although often conceptualized in contradictory terms, the common assumption that
      natural and supernatural explanations are incompatible is psychologically
      inaccurate. Instead, there is considerable evidence that the same individuals use
      both natural and supernatural explanations to interpret the very same events and
      that there are multiple ways in which both kinds of explanations coexist in
      individual minds. Converging developmental research from diverse cultural
      contexts in 3 areas of biological thought (i.e., the origin of species, illness,
      and death) is reviewed to support this claim. Contrary to traditional accounts of
      cognitive development, new evidence indicates that supernatural explanations
      often increase rather than decrease with age and supports the proposal that
      reasoning about supernatural phenomena is an integral and enduring aspect of
      human cognition.

PMID- 22417319
TI  - Dynamics of a supramolecular capsule assembly with pyrene.
AB  - Water-soluble octaacid cavitands (OAs) form dimeric capsules suitable for guest
      incorporation. Our studies reveal that the mechanism of pyrene (Py) binding
      involves the rapid (<1 ms) formation of the Py.OA complex followed by slower
      binding with the second OA. The dissociation of the capsular OA.Py.OA complex
      occurs with a lifetime of 2.7 s, which is 5 orders of magnitude slower than the
      microsecond opening/closing ("breathing") previously observed to provide access
      of small molecules to the encapsulated guest. These different dynamics of the
      capsules have a potential impact on how the chemistry of included guests could be
      altered.

PMID- 22417320
TI  - Association between lymphotoxin beta receptor gene polymorphisms and IgA
      nephropathy in Korean children.
AB  - Lymphotoxin beta receptor (LTBR) is essential for development and organization of
      the secondary lymphoid tissues. To investigate whether LTBR polymorphisms are
      associated with IgA nephropathy (IgAN) in Korean children, One hundred ninety
      nine patients with IgAN and 289 controls were recruited. Two promoter single
      nucleotide polymorphisms (SNPs) (rs3759333, -1387C/T and rs3759334, -1326A/G) and
      one coding SNP (rs2364480, Ala172Ala) in LTBR gene were selected and genotyped by
      direct sequencing. For analysis of data, SNPStats, SPSS 18.0, and Haploview
      version 4.2 were used. Multiple logistic regression models (codominant 1,
      codominant 2, dominant, and recessive models) were performed for odds ratio (OR),
      95% confidence interval (CI), and p value. The rs3759334 was significantly
      associated with IgAN in codominant 1 (G/G vs. A/G, p = 0.025) and dominant (p =
      0.017) models. The A alleles of rs3759334 and rs2364480 were related to risk of
      developing IgAN, respectively (rs3759334, p = 0.015; rs2364480, p = 0.041).
      Haplotypes CGC and TAA in LTBR gene were also associated with IgAN, respectively
      (CGC, p = 0.032 in codominant; TAA, p = 0.008 in codominant, p = 0.009 in
      dominant models). In conclusion, results suggest that LTBR gene polymorphisms may
      be associated with risk of IgAN in Korean children.

PMID- 22417322
TI  - Factors associated with intensiveness of use of child preventive health services
      in Taiwan: a comparative study between cross-cultural immigrant families and
      native-born families.
AB  - OBJECTIVES: To compare intensiveness of use of child preventive health services
      (CPHS) between cross-cultural immigrant families and native-born families in
      Taiwan and to explore factors associated with differences in intensiveness of
      CPHS use. DESIGN: Cross-cultural immigrant families were defined as families
      where the mother was an immigrant from another southeast Asian country. In native
      born families, both parents were Taiwanese-born. Data were collected from 318
      immigrant mothers and 340 native-born mothers of children aged 7 years or younger
      in a cross-sectional survey in central Taiwan. A social determinants framework of
      health inequities was constructed, and ordinal logistic regression models were
      used to examine the effect of four domains of intermediary determinants on the
      relationship between family type and underuse of CPHS: CPHS-related factors,
      medical-related factors, maternal acculturation factors, and
      sociodemographic/socioeconomic characteristics. RESULTS: Cross-cultural immigrant
      families were less likely to intensively use CPHS than native-born families. This
      difference appeared to be mediated by the greater likelihood of having an older
      child or a lower educated father in cross-cultural families. CONCLUSION: Findings
      of this study highlight the importance of promoting health behaviors and
      combating health inequities and social inequalities for cross-cultural immigrant
      families in Taiwan from a sociodemographic/socioeconomic and political context.

PMID- 22417321
TI  - Contemporary rates of severe hypoglycaemia in youth with type 1 diabetes:
      variability by insulin regimen.
AB  - AIMS: To determine incidence rates of severe hypoglycaemia and compare incidence
      rates by insulin regimen in a diverse sample of youth with Type 1 diabetes from
      two sites. METHODS: In this observational study, 255 youth (51% female) aged 9-15
      years receiving varied insulin regimens provided data prospectively for a median
      of 1.2 years. Reported episodes of severe hypoglycaemia, defined as episodes
      requiring help from another person for oral treatment or episodes resulting in
      seizure/coma, and current insulin regimens were collected systematically.
      Incidence rates were calculated and compared according to insulin regimen in
      bivariate and multivariate analyses. RESULTS: At first encounter, participants
      had a median age of 12.2 years (range 9.0-15.0), median diabetes duration of 4.4
      years (range 1.0-13.0) and mean HbA(1c) of 67 +/- 12 mmol/mol (8.3 +/- 1.1%). The
      incidence rate was 37.6/100 patient-years for all severe hypoglycaemia and
      9.6/100 patient-years for seizure/coma. The incidence rate for severe
      hypoglycaemia was 31.8/100 patient-years on continuous subcutaneous insulin
      infusion (pump therapy), 34.4/100 patient-years on basal-bolus injections and
      46.1/100 patient-years on NPH (NPH vs. pump therapy: P = 0.04). The incidence
      rate for seizure/coma was 4.5/100 patient-years on pump therapy, 11.1/100 patient
      years on basal-bolus injections and 14.4/100 patients-years on NPH (NPH vs. pump
      therapy: P = 0.004). In the multivariate analysis, the rate of seizure/coma was
      significantly higher for those on NPH vs. pump therapy (rate ratio 2.9, P =
      0.03). CONCLUSIONS: Rates of severe hypoglycaemia in youth with Type 1 diabetes
      remain high. Pump therapy was associated with lower rates of all severe
      hypoglycaemia and seizure/coma in comparison with NPH.

PMID- 22417323
TI  - The surgical treatment of a large prostatic adenoma: the laparoscopic approach--a
      systematic review.
AB  - PURPOSE: To present a critical overview of the current literature on the role of
      laparoscopy for the surgical treatment of patients with large prostatic adenomas.
      MATERIALS AND METHODS: A MedLine search for peer-reviewed studies on laparoscopic
      simple prostatectomy (LSP) was performed. The clinical studies that reported most
      of the following information were included: number of patients, prostate volume,
      operative time, blood loss, hospital stay, and the duration of catheterization,
      as well as functional outcomes and complications. Articles reporting a mean total
      prostate volume of <80 mL or a mean prostatic adenoma of <60 mL were excluded.
      The review was performed according to the PRISMA statement. RESULTS: Fourteen
      articles on LSP were included in this systematic review with a total of 626
      patients treated. Both transperitoneal and extraperitoneal approaches, as well as
      transvesical and transcapsular routes, have been described. Eleven articles were
      case-series and three were comparative retrospective nonrandomized studies. When
      compared with open simple prostatectomy (OP), LSP is associated with a less blood
      loss and a reduced irrigation requirement, a shorter postoperative
      catheterization period, and a shorter hospital stay, at the expense of an
      extended operative time. The limited number of patients treated, the selection
      biases due to the retrospective nature of several published articles on LSP, and
      the short follow-up periods are evident limits of the literature. I-square test
      demonstrated a high heterogeneity (93%) and consequently a high variability in
      the intervention effects in terms of maximum urinary flow rate (Qmax).
      CONCLUSIONS: Even if LSP seems feasible and safe, there is still limited evidence
      regarding its long-term outcomes compared with OP.

PMID- 22417324
TI  - Brain activation induced by dentine hypersensitivity pain--an fMRI study.
AB  - AIM: Dentine hypersensitivity (DH) is characterized by a short, sharp pain
      arising from exposed dentin. Most published literature reports on peripheral
      neural aspects of this pain condition. The current investigation focused on
      differential cerebral activity elicited by stimulation of sensitive and
      insensitive teeth by means of natural air stimuli. MATERIALS AND METHODS: Five
      graded stimulus strengths were randomly applied by means of a multi-injector air
      jet delivery system, each followed by an individual rating of perceived stimulus
      intensity. Brain activity was analysed by functional magnetic resonance imaging
      (fMRI). RESULTS: Stimulation of sensitive teeth induced significant activation in
      the thalamus, somatosensory cortices (SI & SII), anterior, middle and posterior
      insular cortices, anterior mid cingulate cortex, perigenual anterior cingulate
      cortex and frontal regions (BA10 and BA46). Differential responses to DH and
      painless perceptions were observed in the anterior insula and anterior
      midcingulate cortex. CONCLUSION: For the first time, this fMRI study demonstrates
      the feasibility of investigating cerebral processes related to DH evoked by
      natural (air) stimuli. Our neuroimaging data additionally provide evidence that
      differential activity in the anterior Insula (aIC) and anterior midcingulate
      cortex (aMCC) may represent clinically relevant pain experienced by DH patients.

PMID- 22417325
TI  - Detection of genes regulated by Lmx1b during limb dorsalization.
AB  - Lmx1b is a homeodomain transcription factor that regulates dorsal identity during
      limb development. Lmx1b knockout (KO) mice develop distal ventral-ventral limbs.
      Although induction of Lmx1b is linked to Wnt7a expression in the dorsal limb
      ectoderm, the downstream targets of Lmx1b that accomplish limb dorsalization are
      unknown. To identify genes targeted by Lmx1b, we compared gene arrays from Lmx1b
      KO and wild type mouse limbs during limb dorsalization, i.e., 11.5, 12.5, and
      13.5 days post coitum. We identified 54 target genes that were differentially
      expressed in all three stages. Several skeletal targets, including Emx2,
      Matrilin1 and Matrilin4, demonstrated a loss of scapular expression in the Lmx1b
      KO mice, supporting a role for Lmx1b in scapula development. Furthermore, the
      relative abundance of extracellular matrix-related soft tissue targets regulated
      by Lmx1b, such as collagens and proteoglycans, suggests a mechanism that includes
      changes in the extracellular matrix composition to accomplish limb dorsalization.
      Our study provides the most comprehensive characterization of genes regulated by
      Lmx1b during limb development to-date and provides targets for further
      investigation.

PMID- 22417326
TI  - Color vision: a study of essential tremor cases versus normal controls.
AB  - BACKGROUND AND PURPOSE: Patients with essential tremor (ET) and Parkinson's
      disease (PD) may exhibit overlapping clinical features. Also, a growing number of
      non-motor features are being documented in ET. Color vision abnormalities,
      although well known to occur in PD, have not been studied extensively in ET. We
      assessed color vision in ET cases and controls. We furthermore assessed subgroups
      of ET cases with clinical features that might link them to PD (i.e., ET cases
      with a family history of PD, and ET cases with rest tremor) to determine whether
      these cases had greater color vision abnormalities than ET cases without those
      features. METHODS: Participants were enrolled in a case-control study at Columbia
      University Medical Center. Color discrimination testing was performed using the
      Farnsworth-Munsell 100 Hue test. The total error score (TES) for the hue test was
      determined. RESULTS: The TES was similar in 55 ET cases and 55 controls (144.6 +/
      91.8 vs. 145.6 +/- 96.6, P = 0.96). ET cases with rest tremor (n = 8) were
      similar to ET cases without rest tremor (n = 47) with respect to the TES (117.0
      +/- 73.4 vs. 149.3 +/- 94.4, P = 0.36), as were ET cases with a family history of
      PD (n = 9) versus without (n = 46) (144.4 +/- 57.0 vs. 144.6 +/- 97.6, P =
      0.996). CONCLUSIONS: Although a number of links exist between ET and PD, and non
      motor features have been described in both, a color vision abnormality does not
      seem to be a feature of ET.

PMID- 22417328
TI  - Estimation of HIV incidence in Malawi from cross-sectional population-based sero
      prevalence data.
AB  - ABSTRACT:  BACKGROUND: Incidence is a better measure than prevalence for
      monitoring AIDS, but it is not often used because longitudinal HIV data from
      which incidence can be computed is scarce. Our objective was to estimate the
      force of infection and incidence of HIV in Malawi using cross-sectional HIV sero
      prevalence data from the Malawi Demographic and Health Survey conducted in 2004.
      METHODS: We formulated a recurrence relation of population prevalence as a
      function of a piecewise-constant force of HIV infection. The relation adjusts for
      natural and HIV-induced mortality. The parameters of the recurrence relation were
      estimated using maximum likelihood, and confidence intervals of parameter
      estimates were constructed by bootstrapping. We assessed the fit of the model
      using the Pearson Chi-square goodness of fit test. We estimated population
      incidence from the force of infection by accounting for the prevalence, as the
      force of infection applies only to the HIV-negative part of the population.
      RESULTS: The estimated HIV population incidence per 100,000 person-years among
      men is 610 for the 15-24 year age range, 2700 for the 25-34 group and 1320 for 35
      49 year olds. For females, the estimates are 2030 for 15-24 year olds, 1710 for
      25-34 year olds and 1730 for 35-49 year olds. CONCLUSIONS: Our method provides a
      simple way of simultaneously estimating the incidence rate of HIV and the age
      specific population prevalence for single ages using population-based cross
      sectional sero-prevalence data. The estimated incidence rates depend on the HIV
      and natural mortalities used in the estimation process.

PMID- 22417329
TI  - Pathophysiology of varicocele in male infertility in the era of assisted
      reproductive technology.
AB  - Varicocele is the most common and treatable cause of male infertility. Studies of
      a rat experimental left varicocele model and human testicular biopsy samples have
      shown the involvement of various factors in its pathophysiology. Among them,
      oxidative stress plays a major role in impairing spermatogenesis and sperm
      function. Therefore, in addition to palpation, scrotal ultrasonography and color
      Doppler ultrasound, evaluation of testicular oxidative stress (e.g. scrotal
      temperature is a surrogate parameter) is recommended to enable diagnosis and
      suitable treatment of varicocele. Varicocelectomy increases the fertilization,
      pregnancy and live birth rates, indicating improved sperm function; it is
      therefore important even in couples undergoing intracytoplasmic sperm injection.
      Routine sperm-function tests are warranted to monitor the sperm quality after
      varicocelectomy and consequent improvement in the outcomes of assisted
      reproductive technology. Furthermore, the indications of varicocelectomy in
      assisted reproductive technology should be widened.

PMID- 22417330
TI  - A review on the relation between simulation and improvement in hospitals.
AB  - BACKGROUND: Simulation applications on operations management in hospitals are
      frequently published and claim to support decision-making on operations
      management subjects. However, the reported implementation rates of
      recommendations are low and the actual impact of the changes recommended by the
      modeler has hardly been examined. This paper examines: 1) the execution rate of
      simulation study recommendations, 2) the research methods used to evaluate
      implementation of recommendations, 3) factors contributing to implementation, and
      4) the differences regarding implementation between literature and practice.
      RESULTS: Altogether 16 hospitals executed the recommendations (at least
      partially). Implementation results were hardly reported upon; 1 study described a
      before-and-after design, 2 a partial before and after design. Factors that help
      implementation were grouped according to 1) technical quality, of which data
      availability, validation/verification with historic data/expert opinion, and the
      development of the conceptual model were mentioned most frequently 2) process
      quality, with client involvement and 3) outcome quality with, presentation of
      results. The survey response rate of traceable authors was 61%, 18 authors
      implemented the results at least partially. Among these responses, evaluation
      methods were relatively better with 3 time series designs and 2 before-and-after
      designs. CONCLUSIONS: Although underreported in literature, implementation of
      recommendations seems limited; this review provides recommendations on project
      design, implementation conditions and evaluation methods to increase
      implementation. METHODS: A literature review in PubMed and Business Source Elite
      on stochastic simulation applications on operations management in individual
      hospitals published between 1997 and 2008. From those reporting implementation,
      cross references were added. In total, 89 papers were included. A scoring list
      was used for data extraction. Two reviewers evaluated each paper separately; in
      case of discrepancies, they jointly determined the scores. The findings were
      validated with a survey to the original authors.

PMID- 22417331
TI  - Analytical and sensory characterization of the aroma of "Langhe D.O.C. Nebbiolo"
      wines: influence of the prefermentative cold maceration with dry ice.
AB  - The present work concerns the determination of the volatile compounds, as well as
      the description of the olfactory characteristics, of "Langhe DOC Nebbiolo" wines
      produced through the prefermentative cold maceration with dry ice, on full scale
      (30 quintals) in private cellars. The free volatile compounds and those obtained
      by enzymatic and chemical hydrolysis of the glycosilated precursors were analyzed
      by gas chromatography-mass spectrometry. Among free volatile compounds, a loss of
      alcohols with 6 carbon atoms in the cryo-macerated trials was observed. The cryo
      maceration technique, when correctly applied, increased the floral and fruity
      notes (blackberry, cherry, and plum). This increase is related to the extraction
      of polyphenolic compounds (maceration effect), but no volatile compounds, neither
      in free form, nor produced by enzymatic hydrolysis of the glycosilated
      precursors, can discriminate the wines according to their content of polyphenols.
      Only some compounds produced by chemical hydrolysis of the precursors can
      discriminate the wines (statistically significant differences): 3-hydroxy-beta
      damascone, methylvanillate, and blumenol C. These compounds, however, form during
      aging and do not have any influence on young wines aroma.

PMID- 22417332
TI  - Chemical composition and antioxidant properties of candlenut oil extracted by
      supercritical CO2.
AB  - Candlenut oil was extracted using supercritical CO(2) (SC-CO(2)) with an
      optimization of parameters, by the response surface methodology. The ground
      candlenut samples were treated in 2 different ways, that is, dried in either a
      heat oven (sample moisture content of 2.91%) or dried in a vacuum oven (sample
      moisture content of 1.98%), before extraction. An untreated sample (moisture
      content of 4.87%) was used as a control. The maximum percentage of oil was
      extracted from the heat-oven-dried sample (77.27%), followed by the vacuum-oven
      dried sample (74.32%), and the untreated sample (70.12%). At an SC-CO(2) pressure
      of 48.26 Mpa and 60 min of extraction time, the optimal temperatures for
      extraction were found to be 76.4  degrees C, 73.9  degrees C, and 70.6  degrees C
      for the untreated, heat-oven-dried, and vacuum-oven-dried samples, respectively.
      The heat-oven-dried sample contains the highest percentage of linoleic acid,
      followed by the untreated and vacuum-oven-dried samples. The antiradical activity
      of candlenut oil corresponded to an IC(50) value of 30.37 mg/mL.

PMID- 22417333
TI  - Effect of maturity, processing, and storage on the furanocoumarin composition of
      grapefruit and grapefruit juice.
AB  - Since the early 1990's, grapefruit juice has been implicated in drug interaction
      with various furanocoumarins (FCs) now associated with the effect. Although FCs
      are present in various fruits and vegetables, it is their presence in grapefruit
      that has attracted the most attention. Studies have shown that FCs in grapefruit
      juice can vary significantly and from multiple causes. Most of all, FCs are
      stress-induced molecules, their levels affected by many factors ranging from UV
      exposure to insect infestation. There are also varietal and seasonal factors. In
      this study, juice processing and storage parameters were investigated. Prolonged
      fruit storage prior to processing and most steps involved in juice processing had
      little influence on the levels of 6',7'-dihydroxybergamottin (DHB), paradisin C,
      or bergamottin. However, products that were hot filled or stored at room
      temperature had lower amounts of DHB and paradisin C and higher amounts of
      bergaptol compared to juices that were not hot filled and stored at refrigerated
      temperatures. Both DHB and paradisin C are potent CYP3A4 inhibitors, while
      bergaptol is a very weak inhibitor. Bergamottin amounts decreased to a lesser
      extent. Therefore, grapefruit juice products that were hot filled or have been
      stored at room temperature for an extended period of time will have a reduced
      drug interaction potential.

PMID- 22417334
TI  - Influence of the different oils used in dough formulation on the lipid fraction
      of taralli.
AB  - An experimental investigation was carried out to evaluate the quality of taralli
      as a function of the type of oil used in their dough formulation. To this end, 4
      types of oil (extra virgin olive oil, olive oil, olive-pomace oil, and refined
      palm oil) were utilized to prepare taralli to investigate on the lipid fraction
      degradation and evaluate the taralli acceptability by consumers. The data
      obtained pointed out that taralli manufactured with extra virgin olive oil were
      significantly more appreciated than those made with refined oils due to their
      visual appearance and odor. Moreover, with respect to the other kinds of oil, the
      use of extra virgin olive oil led to significantly lower values (P < 0.05) of
      specific absorption at 232 and 270 nm (K(232) and K(270) , respectively) and of
      triacylglycerol oligopolymers. It also proved to present a much lower content in
      oxidized triacylglycerols and diacylglycerols than olive-pomace oil and refined
      palm oil, respectively. Furthermore, trans fatty acid isomers were absent in
      taralli made with extra virgin olive oil but were constantly present in those
      produced with refined oils.

PMID- 22417335
TI  - Lipase-catalyzed interesterification in packed bed reactor using 2 different
      temperatures.
AB  - Lipase-catalyzed interesterification of high oleic sunflower oil and fully
      hydrogenated soybean oil (70 : 30, wt/ wt) was carried out in a packed bed
      reactor using an immobilized lipase from Thermomyces lanuginosus (Lipozyme TL IM)
      and the effect of a stepwise temperature protocol involving the 2 different
      temperatures, 60 and 70  degrees C, was investigated. The melting point of a fat
      that was incubated at 70  degrees C for 9 min was 57  degrees C, which suggested
      that it should be to employ a lower reaction temperature of 60  degrees C, after
      the first 9 min of the reaction. There were no significant differences (P < 0.05)
      in the conversion degree, triacylglycerol profile, and solid fat content between
      a constant temperature protocol (70  degrees C) and a stepwise temperature
      protocol (a combination of 70 and 60  degrees C). After 50 cycles, the overall
      residual activities of enzymes employed in stepwise temperature protocol were
      significantly (P < 0.05) higher than those of enzymes employed in constant
      temperature protocol.

PMID- 22417336
TI  - Antioxidant and antidiabetic properties of condensed tannins in acetonic extract
      of selected raw and processed indigenous food ingredients from Kenya.
AB  - Recently, tannins have received considerable attention as health-promoting
      component in various plant foods and several studies have reported on its
      nutraceutical properties. However, no study has established the role of condensed
      tannins in indigenous foods of Kenya. Therefore, this study was designed to
      evaluate the antioxidant activity (DPPH and FRAP) and antidiabetic effects (alpha
      amylase and alpha-glucosidase inhibition activities) of condensed tannins in some
      selected raw and traditionally processed indigenous cereals, legumes, oil seeds,
      and vegetables. The condensed tannin content of the grains and vegetables ranged
      between 2.55 and 4.35 g/100 g DM and 1.53 and 5.73 g/100 g DM, respectively. The
      scavenging effect of acetonic extract on DPPH radical ranged from 77% to 90%
      while the reducing power was found to be 31 to 574 mmol Fe(II)/g DM in all the
      investigated food ingredients. The condensed tannin extracts of the analyzed
      samples showed promising antidiabetic effects with potential alpha-amylase and
      alpha-glucosidase inhibition activities of 23% to 44% and 58% to 88%,
      respectively. Condensed tannins extracted from the amaranth grain, finger millet,
      field bean, sunflower seeds, drumstick, and amaranth leaves exerted significantly
      higher antioxidant and antidiabetic activities than other food ingredients. Among
      the traditional processing methods, roasting of grains and cooking of vegetables
      were found to be more suitable mild treatments for preserving the tannin compound
      and its functional properties as opposed to soaking + cooking and blanching
      treatments. The identified elite sources of optimally processed indigenous food
      ingredients with promising results could be used as health-promoting ingredients
      through formulation of therapeutic diets.

PMID- 22417337
TI  - Detection of melamine and cyanuric acid in vegetable protein products used in
      food production.
AB  - The multitude of food recalls in 2007 clearly demonstrated that total nitrogen
      content (SigmaN) determination by means of near-infrared spectroscopy (NIRS) and
      Kjeldahl-based measurements can be deceived, and should no longer be regarded as
      a complete quality assurance program for nutritive-protein evaluations.
      Furthermore, contemporary Canadian-employed analytical tools are precariously
      limited in their ability to effectively assure a product where there is no a
      priori knowledge of the environmental toxin(s) involved. In light of these
      challenges, this study explored a number of analytical techniques used to assess
      and furthermore assure the quality of vegetable protein products (VPPs). Using
      liquid chromatography with tandem mass spectrometry (LC/MS/MS) technologies, a
      combination of VPP-based samples was analyzed for the presence of nitrogen
      bearing environmental toxicants. Of the 52 samples tested, involving an
      assortment of matrices, melamine and cyanuric acid were positively identified (>1
      ng/mL) in 22 and 17 samples, respectively. Subsequent high pressure liquid
      chromatography with ultraviolet/visible (HPLC-UV) amino acid profiling further
      confirmed the adulteration of those materials contaminated with melamine and
      melamine-related compounds. Based on the evidence presented herein, LC/MS/MS in
      combination with HPLC-UV provides for a reliable food safety detection system as
      applied to VPPs. Moreover, HPLC-UV is indispensable as a stand-alone 1st level of
      screening to assess the integrity of a VPP or any nutritive protein-based sample.

PMID- 22417338
TI  - Expanded functionality of modified whey protein dispersions after
      transglutaminase catalysis.
AB  - The functionality of whey dispersions, prepared with a modified whey protein
      concentrate (mWPC) ingredient, was significantly altered after cross-linking with
      microbial transglutaminase (TGase) upon pH adjustment to 8. Test TGase-mWPC
      solutions, pH 8, gelled faster than control mWPC dispersions, as measured in real
      time; whereas, the gelling temperature of pretreated TGase-mWPC samples (37 
      degrees C, 2.5 h) increased from 67.8 to 74.8  degrees C with a minimal change in
      gel strength. Prolonged prior incubation with the enzyme (37  degrees C, 20 h)
      raised the gel strength in both control mWPC and TGase-mWPC dispersions, though
      these values were approximately 2.7 times lower in TGase-mWPC samples.
      Furthermore, the gelling temperature was raised by 9  degrees C after extensive
      polymerization. The water holding capacity was not impacted by enzymatic
      processing while emulsions prepared with TGase-mWPC dispersions proved very
      stable with no evidence of phase separation during storage at room temperature
      for 1 mo. Moreover, the apparent viscosity of TGase-mWPC emulsions exhibited a 10
      fold increase compared to nonenzyme-treated mWPC samples. The particle size was
      nearly 11 MUm in covalently linked TGase-mWPC test fractions compared with 8 MUm
      in nonpolymerized mWPC dispersions. Ultimately, the functional characteristics of
      TGase-mWPC ingredients may be designed to deliver superior performance,
      especially with regard to improving heat and emulsion stability.

PMID- 22417339
TI  - Pomological features, nutritional quality, polyphenol content analysis, and
      antioxidant properties of domesticated and 3 wild ecotype forms of raspberries
      (Rubus idaeus L.).
AB  - The raspberry (Rubus idaeus L.) is an economically important berry crop that
      contains many phenolic compounds with potential health benefits. In this study,
      important pomological features, including nutrient content and antioxidant
      properties, of a domesticated and 3 wild (Yayla, Yavuzlar, and Yedigol) raspberry
      fruits were evaluated. Also, the amount of total phenolics and flavonoids in
      lyophilized aqueous extracts of domesticated and wild ecotypes of raspberry
      fruits were calculated as gallic acid equivalents (GAEs) and quercetin
      equivalents (QE). The highest phenolic compounds were found in wild Yayla ecotype
      (26.66 +/- 3.26 GAE/mg extract). Whilst, the highest flavonoids were determined
      in wild Yedigol ecotype (6.09 +/- 1.21 QA/mg extract). The antioxidant activity
      of lyophilized aqueous extracts of domesticated and wild ecotypes of raspberry
      fruits were investigated as trolox equivalents using different in vitro assays
      including DPPH(*), ABTS(*+), DMPD(*+), and O(*-)(2) radical scavenging
      activities, H(2)O(2) scavenging activity, ferric (Fe(3+)) and cupric ions
      (Cu(2+)) reducing abilities, ferrous ions (Fe(2+)) chelating activity. In
      addition, quantitative amounts of caffeic acid, ferulic acid, syringic acid,
      ellagic acid, quercetin, alpha-tocopherol, pyrogallol, p-hydroxybenzoic acid,
      vanillin, p-coumaric acid, gallic acid, and ascorbic acid in lyophilized aqueous
      extracts of domesticated and wild ecotypes of raspberry fruits were detected by
      high-performance liquid chromatography and tandem mass spectrometry (LC-MS-MS).
      The results clearly show that p-coumaric acid is the main phenolic acid
      responsible for the antioxidant and radical scavenging activity of lyophilized
      aqueous extracts of domesticated and wild ecotypes of raspberry fruits.

PMID- 22417340
TI  - Effect of season on fatty acid composition and n-3/n-6 ratios of zander and carp
      muscle lipids in Altinapa Dam Lake.
AB  - In this study, seasonal variations on total fatty acid composition of carp,
      Cyprinus carpio, and zander, Sander lucioperca, muscle lipids in Altinapa Dam
      Lake were determined. Fish samples in 2 seasons (summer and winter) were obtained
      from Altinapa Dam Lake in Konya, Turkey. Polyunsaturated fatty acids were found
      to be higher during the cold season than in the hot both in zander and carp.
      Whereas the Docosahexaenoic acid was high in zander both in summer and winter, in
      carp it was high only during wintertime. Zander contained more n-3 fatty acids
      during the cold season compared to carp. Especially, the n-3:n-6 ratios in zander
      were 3.89 and 3.84 in summer and winter, respectively. In conclusion, seasonal
      variations affected fatty acid composition of zander and carp in Altinapa Dam
      Lake.

PMID- 22417341
TI  - Yield and quality effects of electroplasmolysis and microwave applications on
      carrot juice production and storage.
AB  - Electroplasmolysis as a pretreatment and microwave heating as an alternative to
      traditional heating were used in carrot juice production and the effects of these
      electrical methods on juice quality were investigated. Electroplasmolysis and
      microwave applications were optimized by response surface methodology. Optimum
      conditions were these: voltage gradient of 22.2 V/cm and treatment time of 60 s
      for electroplasmolysis, and flow rate of 90 mL/min with power of 900 W for
      microwave heating. Production of carrot juice was carried out by using these
      optimum conditions. After production, carrot juice samples were stored for 4 mo
      at +4  degrees C and analyses were performed at monthly intervals. As a result of
      electroplasmolysis, a 9.7% increase in juice yield was obtained. In addition,
      100% pectin methylesterase inactivation was found with the microwave heating
      application. The results showed that the highest values for quality
      characteristics, such as antioxidant capacity and total pectin, total phenolic,
      and total carotenoid contents, were obtained with the combined applications of
      the electrical methods. In addition, these quality characteristics were protected
      better in the group of combined applications of the electrical methods
      (electroplasmolysis + microwave) during storage.

PMID- 22417342
TI  - Antioxidant capacity changes of 3 cultivar Chinese pomegranate (Punica granatum
      L.) juices and corresponding wines.
AB  - This study investigated the antioxidant capacities that included Ferric reducing
      antioxidant power (FRAP), 1, 1-diphenyl-2-picryl hydrazine (DPPH), .OH and O(2.)(
      )-scavenging abilities, total polyphenols (TP) and total anthocyanins (TA) in
      pomegranate (Punica granatum L.) juice (PJ) and pomegranate wine (PW). The
      correlations among them were also analyzed. Both PJ and PW showed significantly
      high TP and antioxidant capacities, but some differences existed among these
      cultivars. There was 1596.67 mg/L TP found in sweet PJ, while sour PJ showed the
      highest titratable acidity of 35.90 g/L and lowest pH value at 2.56. Red PJ was
      found to have the highest TA (82.26 mg/L) in the 3 cultivars. Sweet PJ showed
      higher DPPH-scavenging ability and higher FRAP than others. Both PJ and PW
      exhibited high and relatively stable .OH-scavenging abilities, in which sour PJ
      and sour PW had higher O(2.)(-) scavenging capacity than others. Significant
      positive correlations were observed among TP, DPPH, and FRAP in both PJ and PW. A
      high correlation between antioxidant capacities and TP indicated that phenolic
      compounds were major contributors to the high antioxidant activity of PJ and PW.

PMID- 22417343
TI  - Lipid and protein oxidation of chicken breast rolls as affected by dietary
      oxidation levels and packaging.
AB  - The objective of this study was to determine the effects of dietary treatment and
      packaging on the oxidative stability of breast rolls. A total of 120 4-wk-old
      broiler chickens were randomly assigned to control, oxidized diet (5% oxidized
      oil, PV = 100), or antioxidants-added diet (500 IU vitamin E + 200 ppm BHA) and
      fed for 2 wk. Breast muscles were separated from the carcasses and breast rolls
      were prepared. The rolls were cooked in a smoke house (85  degrees C) to an
      internal temperature of 74  degrees C, cooled, sliced to 2-cm thick pieces,
      individually packaged in oxygen permeable bags or vacuum-packaged in oxygen
      impermeable bags, and stored in a 4  degrees C cold room for 7 d. Lipid, protein
      oxidation and volatiles were determined at 1, 4, and 7 d of storage. Dietary
      supplementation of antioxidants significantly reduced lipid oxidation (TBARS) and
      protein oxidation (carbonyls) in breast rolls, and the effect of dietary
      antioxidants on lipid oxidation was more pronounced than protein oxidation.
      Chicken breast rolls from antioxidants treatment group produced significantly
      lower amounts of hexanal and pentanal than those from control and oxidized oil
      treatments (P < 0.05). However, dietary oxidized oil did not increase lipid and
      protein oxidation in breast rolls. Vacuum-packaging significantly delayed the
      onset of lipid oxidation and protein oxidation in chicken rolls during 7-day
      refrigerated storage (P < 0.05). Therefore, it is suggested that appropriate use
      of dietary supplementation of antioxidants in combination with packaging could
      minimize lipid oxidation in chicken breast rolls.

PMID- 22417344
TI  - Effect of thermal and high-pressure processing on the nutritional value and
      quality attributes of a nectarine puree with industrial origin during the
      refrigerated storage.
AB  - The application of hydrostatic high pressure on an industrial line of nectarine
      (Prunus persica L.) purees was assessed in comparison with the traditional
      thermal treatment of pasteurization. Changes after thermal processing (85 
      degrees C, 5 min) and after high-pressure processing (HPP: 450 or 600 MPa for 5
      or 10 min) and during the refrigerated storage (60 d) of an industrially produced
      nectarine puree were evaluated. Conventional heat pasteurization as well as HPP
      showed similar microorganisms' inactivation and maintained the microbial
      stability of purees until the end of the refrigerated storage (60 d). In general,
      thermally treated puree and HP-treated puree at 600 MPa showed more intense color
      changes after processing than the other treatment. In addition, thermally treated
      puree showed more intense color changes during storage than HPP. The highest
      carotenoids extractability was found in those purees treated at the lowest high
      pressure-treatment intensity and holding time (450 MPa/5 min), but at the end of
      the storage (day 60), no differences in individual or total carotenoid levels
      were found between the purees. HPP at 600 MPa/10 min showed the highest
      polyphenols content after the treatment and during the storage. At day 0,
      significantly higher values were found of total antioxidant activity in puree HP
      treated at 450 MPa/10 min than in untreated puree; while at the end of the
      storage, HP-treated puree at 600 MPa/10 min had the highest antioxidant activity.
      Hydrostatic high-pressure application in the industrial line of nectarine puree
      presented some advantages compared to the thermal treatment; however, some of the
      changes found were lessen during the storage period. In addition, more studies
      need to be carried out for HP-treatment intensity optimization.

PMID- 22417345
TI  - Structural changes in marinated fillets of gilthead sea bream (Sparus aurata L.)
      during vacuum storage at refrigerated temperature.
AB  - Fillets of Sparus aurata were marinated in a mixture of salt (5.5%) and citric
      acid (48.9 g/kg) for 1 h, then vacuum packed and refrigerated for 1, 5, 16, and
      21 d. Structural and ultrastructural parameters were evaluated in 6 specimens per
      time period. At day 1, the preservative solution appeared among the muscle
      fibers, thus increasing the interfibrillar spaces; cytoplasmic organelles were
      swollen and the sarcolemma-endomysium appeared very altered and electron-dense.
      At 5 to 10 d, the marinade solution had penetrated into the muscle fibers. The
      subsarcolemmal and intermyofibrillar spaces were dilated and granular lines of
      electron-dense material appeared among the fibers. From 16 d, broad
      interfibrillar spaces were occupied by granular material derived from denatured
      sarcolemma-endomysium and denatured myofibrils. Sarcomeres were already altered
      from initial stages, mainly at the I-band level. The Z-line also appeared
      disrupted. Such alterations were more severe from 10 d on, such that most of the
      sarcomeres showed disintegration of myofilaments.

PMID- 22417346
TI  - Comparative study of phenolic compounds and antioxidant activity in different
      species of cherries.
AB  - A new spectrometric method ultra performance liquid chromatography-tandem mass
      spectrometric with high precision and rapid analysis was developed to separate 17
      phenolic compounds. Different species of cherries, including 10 sweet cherry
      (Prunus avium L.) cultivars, a tart cherry (P. cerasus L.) rootstock (CAB), and a
      hybrid rootstock 'Colt' (P. avium * P. pseudocerasus), were analyzed for
      phenolics contents by this method. The results showed that significant
      differences were observed among the phenolic compound contents in different
      cherry species. In 10 sweet cherry cultivars, the contents of neochlorogenic acid
      and cyanidin-3O-rutinoside were much higher in red-colored fruits (for example,
      64.60 and 44.50 mg/100 g fresh weight in Burlat, respectively) than those in
      bicolored ones. Principal component analysis revealed that cyanidin-3O-rutinoside
      was an effective index for grouping the cultivars with similar species and fruit
      colors. Moreover, there were strong positive correlations between phenolics
      content and antioxidant activity, which was higher in red-colored cherries.

PMID- 22417347
TI  - Development and validation of an HPLC method for the determination of thiamine
      and riboflavin in green leafy vegetables using clara-diastase.
AB  - There is no literature on the use of the currently available form of clara
      diastase (>= 35 U/mg; Fluka Product No. 86959) in the analysis of vitamins B(1)
      and B(2) . Consequently, a method for the determination of total riboflavin and
      total thiamine in green leafy vegetables by high-pressure liquid chromatography
      (HPLC) following sample preparation by sequential acid hydrolysis, enzymatic
      hydrolysis with clara-diastase >= 35 U/mg, and for B1, derivatization to
      thiochrome, was developed and validated. Prepared samples are run at 35  degrees
      C on a 250 * 4.6 mm column of 5 MUm Kromasil 100 C(18) , using a 0.8 mL/min flow
      of a 72:28 mixture of 5 mmol/L ammonium acetate and methanol as mobile phase and
      fluorescence detection. The linear response ranges and limits of detection are,
      respectively, 3.0 to 60.0 and 0.15 ng/mL for B(1) , and 3.1 to 155.0 and 0.103
      ng/mL for B(2) . Of the 4 green leafy vegetables examined, young turnip tops had
      the highest B(1) and B(2) levels (0.19 and 0.20 mg/100 g fresh weight), followed
      by spinach (0.12 and 0.09 mg/100 g), lettuce (0.11 and 0.05 mg/100 g), and chard
      (0.04 mg/100 g).

PMID- 22417348
TI  - Astaxanthin preparation by lipase-catalyzed hydrolysis of its esters from
      Haematococcus pluvialis algal extracts.
AB  - Five of 8 fungal lipases screened were found to effectively hydrolyze astaxanthin
      esters from Haematococcus pluvialis algal cell extracts. Among these, an alkaline
      lipase from Penicillium cyclopium, expressed in Pichia pastoris, had the highest
      enzymolysis efficiency. Tween80 was shown to be an effective emulsifier in this
      lipase hydrolysis system for the 1st time. A series of experiments were performed
      to find optimal conditions for hydrolysis (pH, temperature, reaction time, lipase
      dosage). In the optimal reaction system, Tween80 and H. pluvialis extracts (mass
      ratio 1:1) were emulsified and added to the above lipase at a dosage of 4.6 U/MUg
      (relative to total carotenoids), in phosphate buffer (0.1 M, pH 7.0), and
      incubated at 28  degrees C for 7 h, with agitation at 180 rpm. The free
      astaxanthin recovery ratio under these conditions was 63.2%.

PMID- 22417349
TI  - Use of Mucor miehei lipase to improve functional properties of yolk-contaminated
      egg whites.
AB  - Egg yolk contamination of egg whites continues to be a serious problem in the egg
      industry. The ability of egg whites to form stable and voluminous foams is
      greatly inhibited by yolk contamination, even at very low levels, between 0.01%
      and 0.2% w/w yolk in white. Experiments were conducted to determine if Mucor
      miehei lipase could regenerate the functional properties of yolk-contaminated egg
      whites. Lipase from M. miehei and colipase from porcine pancreas were added to
      yolk-contaminated (0.2%, w/w) egg white samples to hydrolyze triglycerides
      originating from egg yolk. Enzymatic hydrolysis of triacylglycerols was confirmed
      using thin-layer chromatography. Treatment of yolk-contaminated samples with
      lipase and colipase yielded significant (P < 0.05) improvements in a number of
      the functional properties, including the final foam volume, foam capacity, and
      foaming power. These functional properties showed complete restoration to control
      levels. However, foam stability and foam drainage levels were not statistically
      different from yolk-contaminated samples that had not been enzymatically treated.
      Enzyme-treated yolk-contaminated egg whites were also tested in angel food cakes.
      Enzyme-treated, yolk-contaminated egg whites performed similarly to non-yolk
      contaminated control, and much better than yolk-contaminated sample in angel food
      cakes. The results show that most negative effects of yolk contamination can be
      reversed by treatment with Mucor miehei lipase and colipase.

PMID- 22417350
TI  - Phytochemicals characterization of solvent extracts from taro-scented japonica
      rice bran.
AB  - The major phytochemicals and antioxidant properties of taro-scented rice bran
      (TaiNung 71; TN71) extracts using 3 different solvents are characterized. Some
      progress is realized in creating an economic value for rice bran that has long
      been considered an agricultural waste. Various solvent extracts reveal the
      presence of phenolic compounds, oryzanols, tocopherols, and tocotrienols. Ethyl
      acetate (EtOAc) can extract more oryzanols (1.55 +/- 0.20 g/kg rice bran).
      Meanwhile, the methanol (MeOH) extract possesses a higher yield in total contents
      (15.42 +/- 1.41 g/kg bran), which includes phenolic compounds (2.69 +/- 0.29 g
      gallic acid equivalent/kg bran), tocopherols (251 +/- 26 mg/kg bran) and
      tocotrienols (111 +/- 4 mg/kg bran). The MeOH extract exhibits more effective
      antioxidant activity against various oxidative systems in vitro, including the
      inhibition of linoleic acid peroxidation (33.89%), scavenging of DPPH radicals
      (83.88%), and reducing power. It is found that the yield, total content in
      phenolic compounds and tocols of the extracts increase with increasing Synder's
      polarity value and viscosity, which can then be used as the indices in isolation
      of the desired rice bran phytochemicals extracts.

PMID- 22417351
TI  - Changes of hydrogen peroxide and radical-scavenging activity of raspberry during
      osmotic, convective, and freeze-drying.
AB  - This study was conducted to investigate the influence of different drying
      treatments on antioxidant (AO) activity and phenolic content of raspberry (Rubus
      idaeus), cultivar Willamette. Whole raspberry fruits were dried convectively (air
      drying), osmotically, and freeze-dried. Acetone-water extracts of fresh and dried
      raspberries were assessed for total phenolic content by standard Folin-Ciocalteau
      method. Two AO assays were applied, a recently developed direct current (DC)
      polarographic assay based on decrease of anodic oxidation current of hydrogen
      peroxide and widely used radical scavenge against the 1,1-diphenyl-2
      picrylhydrazyl (DPPH). Strong correlation has been obtained between both AO
      assays and total phenolic content. In addition, some individual phenolic
      compounds present in raspberry have been assessed using DPPH and DC polarographic
      assay. Comparison and evaluation of drying methods has been based on preservation
      of AO activity and total phenolic content. Obtained results confirmed superiority
      of freeze-drying; convective drying caused slight changes while osmotic
      dehydration showed a significant decrease of phenolic compounds and AO activity.

PMID- 22417352
TI  - Free fatty acids and oxidative changes of a raw goat milk cheese through
      maturation.
AB  - Free fatty acids (FFA) and lipid and protein oxidation changes were studied
      throughout maturation process of a raw goat milk cheese with protected
      designation of origin. Cheeses were analyzed at 4 different times of maturation,
      at 1, 30, 60, and 90 d. All FFA significantly increased during maturation and the
      relative increase was higher for long-chain than medium- or short-chain FFA. At
      the end of maturation, oleic (C18:1 n9), butyric (C4:0), and palmitic (C16:0)
      acids were the most abundant. The higher levels of short-chain fatty acids (SCFA)
      regarding total FFA obtained at the end of Ibores cheese ripening compared with
      other raw goat milk cheeses, highlight the notable role of SCFA on the flavor of
      this cheese owing to their low-odor thresholds. Lipid oxidation values
      significantly increased during maturation process but low levels of
      malondialdehyde were reported; however, protein oxidation did not significantly
      change during ripening.

PMID- 22417353
TI  - Standardization of domestic frying processes by an engineering approach.
AB  - An approach was developed to enable a better standardization of domestic frying
      of potato products. For this purpose, 5 domestic fryers differing in heating
      power and oil capacity were used. A very defined frying process using a highly
      standardized model product and a broad range of frying conditions was carried out
      in these fryers and the development of browning representing an important quality
      parameter was measured. Product-to-oil ratio, oil temperature, and frying time
      were varied. Quite different color changes were measured in the different fryers
      although the same frying process parameters were applied. The specific energy
      consumption for water evaporation (spECWE) during frying related to product
      amount was determined for all frying processes to define an engineering parameter
      for characterizing the frying process. A quasi-linear regression approach was
      applied to calculate this parameter from frying process settings and fryer
      properties. The high significance of the regression coefficients and a
      coefficient of determination close to unity confirmed the suitability of this
      approach. Based on this regression equation, curves for standard frying
      conditions (SFC curves) were calculated which describe the frying conditions
      required to obtain the same level of spECWE in the different domestic fryers.
      Comparison of browning results from the different fryers operated at conditions
      near the SFC curves confirmed the applicability of the approach.

PMID- 22417354
TI  - Relationship between functional properties and aggregation changes of whey
      protein induced by high pressure microfluidization.
AB  - Aggregation changes of whey protein induced by high-pressure microfluidization
      (HPM) treatment have been investigated in relation with their functional
      properties. Whey protein was treated with HPM under pressure from 40 to 160 MPa.
      Functional properties (solubility, foaming, and emulsifying properties) of whey
      protein concentrate (WPC) ultrafiltered from fluid whey were evaluated. The
      results showed significant modifications in the solubility (30% to 59%) and
      foaming properties (20% to 65%) of WPC with increasing pressure. However,
      emulsifying property of WPC treated at different pressures was significantly
      worse than untreated sample. To better understand the mechanism of the
      modification by HPM, the HPM-induced aggregation changes were examined using
      particle size distribution, scanning electron microscopy, and hydrophobicity. It
      was indicated that HPM induced 2 kinds of aggregation changes on WPC:
      deaggregation and reaggregation of WPC, which resulted in the changes of
      functional properties of WPC modified by HPM.

PMID- 22417355
TI  - Microencapsulation of menhaden fish oil containing soluble rice bran fiber using
      spray drying technology.
AB  - Emulsion (EFMO) containing purified menhaden oil (PMO) and soluble rice bran
      fiber (SRBF) was dried in a pilot scale spray dryer and produced
      microencapsulated PMO with SRBF (MFMO). EFMO had well isolated spherical droplets
      with the size of 1 to 10 MUm and showed pseudoplastic fluid and viscoelastic
      characteristics. EFMO had lower lipid oxidation than the emulsion containing PMO
      without SRBF when both emulsions were stored at 20 and 40  degrees C for 88 h,
      which indicated that the SRBF reduced the lipid oxidation in the EFMO. The
      estimated MFMO production rate (3.45 * 10(-5) kg dry solids/s) was higher than
      the actual production rate (2.31 * 10(-5) kg dry solids/s). The energy required
      to spray dry the EFMO was 12232 kJ/kg of emulsion. EPA and DHA contents of MFMO
      were 11.52% and 4.51%, respectively. The particle size of 90% MFMO ranged from 8
      to 62 MUm, and the volume-length diameter of MFMO was 28.5 MUm.

PMID- 22417356
TI  - Shrimp processing assessed by low field nuclear magnetic resonance, near infrared
      spectroscopy, and physicochemical measurements--the effect of polyphosphate
      content and length of prebrining on shrimp muscle.
AB  - The effect of using polyphosphates during prebrining and the effect of prebrining
      time of cold water shrimp (Pandalus borealis) was studied with low field nuclear
      magnetic resonance (LF-NMR) transverse relaxation time measurements (benchtop and
      unilateral) and near infrared (NIR) spectroscopy with the aim of improving shrimp
      processing. Strong calibrations were obtained for moisture content and water
      holding capacity (WHC) using the NIR technique. Multivariate analysis indicated
      significant correlations between benchtop NMR parameters and moisture content and
      WHC, as measured with physicochemical methods and NIR spectroscopy. Significant
      correlations were also observed between NMR parameters and muscle pH, protein
      content, and phosphate content. The study showed that LF-NMR contribute to
      improved understanding of the shrimp brining process and to improved process
      control on-line or at-line, especially in combination with NIR measurements.
      However, optimization of the unilateral device is necessary.

PMID- 22417357
TI  - Characterization of carbohydrate-protein matrices for nutrient delivery.
AB  - Amorphous carbohydrates may show glass transition and crystallization as a result
      of thermal or water plasticization. Proteins often affect the state transitions
      of carbohydrates in carbohydrate-protein systems. Water sorption behavior and
      effects of water on glass transition and crystallization in freeze-dried lactose,
      trehalose, lactose-casein (3: 1), lactose-soy protein isolate (3:1), trehalose
      casein (3:1), and trehalose-soy protein isolate (3:1) systems were studied. Water
      sorption was determined gravimetrically as a function of time, and Brunauer
      Emmett-Teller (BET) and Guggenheim-Anderson-de Boer (GAB) models were fitted to
      the experimental data. Glass transition temperature (T(g)) and instant
      crystallization temperature (T(ic)) in anhydrous and water plasticized systems
      were measured using differential scanning calorimetry (DSC). The Gordon-Taylor
      equation was used to model water content dependence of the T(g) values. The
      critical water content and water activity (a(w)) at 24  degrees C were calculated
      and crystallization of lactose and trehalose in the systems was followed at and
      above 0.54 a(w). Carbohydrate-protein systems showed higher amounts of sorbed
      water and less rapid sugar crystallization than pure sugars. A greater sugar
      crystallization delay was found in carbohydrate-casein systems than in
      carbohydrate-soy protein isolate systems. The T(g) and T(ic) values decreased
      with increasing water content and a(w). However, higher T(ic) values for lactose
      protein systems were found than for lactose at the same a(w). Trehalose showed
      lower T(ic) value than lactose at 0.44 a(w) but no instant crystallization was
      measured below 0.44 a(w). State diagrams for each system are useful in selecting
      processing parameters and storage conditions in nutrient delivery applications.

PMID- 22417358
TI  - Controlled exogenous enzyme imbibition and activation in whole chickpea seed
      enzyme reactor (SER).
AB  - Chickpeas are of excellent quality (protein, vitamins, minerals, unsaturated
      fatty acids) and very low in phytoestrogen, making them a potentially promising
      source for vegetarian-based infant formula (VBIF). However, their high starch and
      fiber concentration could hinder their utilization for infants. To overcome this
      natural shortcoming, a solid-state "enzymation" (SSE) process was developed in
      which imbibition of exogenous enzyme facilitates hydrolysis within the intact
      chickpea seed. The process was termed seed enzyme reactor (SER). Liquid
      imbibition data of dry chickpeas during soaking were fitted with the Weibull
      distribution model. The derived Weibull shape parameter, beta, value (0.77 +/-
      0.11) indicated that the imbibition mechanism followed Fickian diffusion.
      Imbibition occurred through the coat and external layers. The process was tested
      using green fluorescent protein (GFP) as an exogenous marker, and involved
      soaking, thermal treatment, peeling, microwave partial drying, rehydration in
      enzyme solution, and SSE at an adjusted pH, time, and temperature. Amylases, or a
      combination of amylases and cellulases, resulted in significant carbohydrate
      hydrolysis (23% and 47% of the available starch, respectively). In addition,
      chickpea initial raffinose and stachyose concentration was significantly reduced
      (91% and 92%, respectively). The process could serve as a proof of concept,
      requiring additional development and optimization to become a full industrial
      application.

PMID- 22417359
TI  - Fish protein decreases serum cholesterol in rats by inhibition of cholesterol and
      bile acid absorption.
AB  - Fish protein has been shown to decrease serum cholesterol content by inhibiting
      absorption of cholesterol and bile acid in laboratory animals, though the
      mechanism underlying this effect is not yet fully understood. The purpose of this
      study was to elucidate the mechanism underlying the inhibition of cholesterol and
      bile acid absorption following fish protein intake. Male Wistar rats were divided
      into 2 dietary groups of 7 rats each, 1 group receiving a diet consisting of 20%
      casein and the other receiving a diet consisting of 10% casein and 10% fish
      protein. Both experimental diets also contained 0.5% cholesterol and 0.1% sodium
      cholate. After the rats had been on their respective diets for 4 wk, their serum
      and liver cholesterol contents and fecal cholesterol, bile acid, and nitrogen
      excretion contents were measured. Fish protein consumption decreased serum and
      liver cholesterol content and increased fecal cholesterol and bile acid excretion
      and simultaneously increased fecal nitrogen excretion. In addition, fish protein
      hydrolyzate prepared by in vitro digestion had lower micellar solubility of
      cholesterol and higher binding capacity for bile acids compared with casein
      hydrolyzate. These results suggest that the hypocholesterolemic effect of fish
      protein is mediated by increased fecal cholesterol and bile acid excretion, which
      is due to the digestion products of fish protein having reduced micellar
      solubility of cholesterol and increased bile acid binding capacity.

PMID- 22417360
TI  - Genotypic variation and relationships between quality traits and trace elements
      in traditional and improved rice (Oryza sativa L.) genotypes.
AB  - In this study, we assessed the extent of genotypic differences among rice
      genotypes for grain size, milling quality, cooking properties, protein, and the
      mineral contents of Fe, Zn, Mn, and Cu in unpolished rice varieties. Further,
      relationship among grain quality traits and mineral contents was determined. The
      results showed that the visible difference could be found in the mineral contents
      among rice genotypes studied. The contents of Fe and Zn in traditional genotypes
      were significantly higher than those of improved cultivars. There was a negative
      correlation between grain yield and mineral contents. However, Fe, Zn, Mn, and Cu
      contents appeared to be positively correlated. The relationships between mineral
      element contents and cooking quality traits viz., kernel length after cooking and
      kernel linear elongation ratio were positively correlated, indicated the role of
      micronutrients in cooking quality traits. Both Fe and Cu contents were correlated
      positively and significantly with head rice recovery. The eigen values of 1st 6
      principal components (PC) were > 1.0. The present study suggests that breeding
      for high minerals will be probably realistic.

PMID- 22417361
TI  - Yogurt can beneficially affect blood contributors of cardiovascular health status
      in hypertensive rats.
AB  - Cardiovascular disease is the single leading cause of death in the world and
      elevated blood pressure is one of the major independent risk factors. Angiotensin
      I-converting enzyme-inhibitors have received considerable attention for their
      effectiveness in both the prevention and the treatment of hypertension. To
      confirm the antihypertensive effect, the influence of yogurt- and probiotic
      yogurt-based diets on the weight gain, serum lipid profile, and blood pressure
      (BP) were investigated in spontaneously hypertensive rats (14 wk old). A total of
      3 dietary treatments were fed for 8 wk: skim milk diet (Feed-C), skim milk diet
      supplemented with freeze dried low fat yogurt (Feed-Y), and with freeze dried low
      fat probiotic yogurt (Feed-PY). The total weight gain for the 8-wk period was
      maximum in rats fed Feed-C (90 g) followed by those fed Feed-PY (85.7 g) and Feed
      Y (78.7 g), indicating that the overall weight gains were lesser (statistically
      non-significant) in the groups fed yogurt containing diets. At the end of the
      feeding period the reduction in systolic BP of rats fed Feed-Y was 3.7% (-9.5 mm
      Hg) and 2.7% (-6.4 mm Hg) in those fed Feed-PY while reduction in diastolic BP
      was 30% (-9.4 mm Hg) and 44% (-13.8 mm Hg), respectively, in comparison to those
      fed Feed-C. The levels of total cholesterol and low density lipoprotein
      cholesterol of rats fed the supplemented diets were lower than those fed Feed-C
      while no changes in the levels of high density lipoprotein-cholesterol were
      observed. It was concluded that feeding diets supplemented with yogurts exhibited
      antihypertensive and hypocholesterolemic effects in spontaneously hypertensive
      rats.

PMID- 22417362
TI  - Detection of viable Salmonella in lettuce by propidium monoazide real-time PCR.
AB  - Contamination of lettuce by Salmonella has caused serious public health problems.
      Polymerase chain reaction (PCR) allows rapid detection of pathogenic bacteria in
      food, but it is inaccurate as it might amplify DNA from dead target cells as
      well. This study aimed to investigate the stability of DNA of dead Salmonella
      cells in lettuce and to develop an approach to detecting viable Salmonella in
      lettuce. Salmonella-free lettuce was inoculated with heat-killed Salmonella
      Typhimurium cells and stored at 4  degrees C. Bacterial DNA extracted from the
      sample was amplified by real-time PCR targeting the invA gene. Our results
      indicate that DNA from the dead cells remained stable in lettuce for at least 8
      d. To overcome this limitation, propidium monoazide (PMA), a dye that can
      selectively penetrate dead bacterial cells and cross-link their DNA upon light
      exposure, was combined with real-time PCR. Lettuce samples inoculated with
      different levels of dead or viable S. Typhimurium cells were treated or untreated
      with PMA before DNA extraction. Real-time PCR suggests that PMA treatment
      effectively prevented PCR amplification from as high as 10(8) CFU/g dead S.
      Typhimurium cells in lettuce. The PMA real-time PCR assay could detect viable
      Salmonella at as low as 10(2) CFU/mL in pure culture and 10(3) CFU/g in lettuce.
      With 12-h enrichment, S. Typhimurium of 10(1) CFU/g in lettuce was detectable. In
      conclusion, the PMA real-time PCR assay provides an alternative to real-time PCR
      assay for accurate detection of Salmonella in food.

PMID- 22417363
TI  - GC-MS based metabolomics for rapid simultaneous detection of Escherichia coli
      O157:H7, Salmonella Typhimurium, Salmonella Muenchen, and Salmonella Hartford in
      ground beef and chicken.
AB  - A metabolomic-based method for rapid detection of Escherichia coli O157:H7,
      Salmonella Hartford, Salmonella Typhimurium, and Salmonella Muenchen in
      nonselective media was developed. All pathogenic bacteria were grown in tryptic
      soy broth (TSB) at 37  degrees C followed by metabolite quantification at 2-h
      intervals for 24 h. Results were compared with the metabolite profiles similarly
      obtained with E. coli K12, Pseudomonas aeruginosa, Staphylococcus aureus,
      Saccharomyces cereviseae, and Aspergillus oryzae grown individually or as a
      cocktail under the same conditions. Principal component analysis (PCAS)
      discriminated pathogenic microorganisms grown in TSB. Metabolites responsible of
      PCAS classification were dextrose, cadaverine, the aminoacids L-histidine,
      glycine, and L-tyrosine, as well as the volatiles 1-octanol, 1-propanol,
      1butanol, 2-ethyl-1-hexanol, and 2,5-dimethyl-pyrazine. Partial least square
      (PLS) models based on the overall metabolite profile of each bacteria were able
      to detect the presence of Escherichia coli O157:H7 and Salmonella spp. at levels
      of approximately 7 +/- 2 CFU/25 g of ground beef and chicken within 18 h.

PMID- 22417364
TI  - Differentiation between Aspergillus flavus and Aspergillus parasiticus from pure
      culture and aflatoxin-contaminated grapes using PCR-RFLP analysis of aflR-aflJ
      intergenic spacer.
AB  - Aflatoxins (AFs) represent the most important single mycotoxin-related food
      safety problem in developed and developing countries as they have adverse effects
      on human and animal health. They are produced mainly by Aspergillus flavus and A.
      parasiticus. Both species have different aflatoxinogenic profile. In order to
      distinguish between A. flavus and A. parasiticus, gene-specific primers were
      designed to target the intergenic spacer (IGS) for the AF biosynthesis genes,
      aflJ and aflR. Polymerase chain reaction (PCR) products were subjected to
      restriction endonuclease analysis using BglII to look for restriction fragment
      length polymorphisms (RFLPs). Our result showed that both species displayed
      different PCR-based RFLP (PCR-RFLP) profile. PCR products from A. flavus cleaved
      into 3 fragments of 362, 210, and 102 bp. However, there is only one restriction
      site for this enzyme in the sequence of A. parasiticus that produced only 2
      fragments of 363 and 311 bp. The method was successfully applied to contaminated
      grapes samples. This approach of differentiating these 2 species would be
      simpler, less costly, and quicker than conventional sequencing of PCR products
      and/or morphological identification.

PMID- 22417365
TI  - Galactooligosaccharides: novel components of designer foods.
AB  - Since introduction of functional foods, commercialization of the traditionally
      used probiotics has ushered in more followers into the new fraternity of
      sophisticated, health-conscious consumers. In 1995, this was followed by the
      first introduction of prebiotics. Prebiotics are defined as "a non-digestible
      feed supplement, beneficially affecting the host by selectively stimulating
      growth and/or activity in one or a limited number of bacteria in the colon." The
      number of new product introductions with prebiotics has steeply increased over
      the last few years. Paradoxically, probiotics have limited applications as these
      cannot be used in wide range of food products because of their viability issue.
      Fortunately, prebiotics do not suffer from any such constraint and can be used in
      a wide range of food products. Probiotics do not have a long shelf life in their
      active form. In most cases, refrigeration is required to maintain the shelf life.
      While probiotics are predominantly used in fermented dairy products, the use of
      prebiotics has expanded into other food categories. Prebiotics have successfully
      been incorporated in a wide variety of human food products such as baked goods,
      sweeteners, yoghurts, nutrition bars, and meal replacement shakes. For instance,
      the introduction of galacto-oligosaccharides (GOS) into baby foods has been very
      successful. GOS, which are identical to the human milk oligosaccharides, has
      emerged with strong clinical support for both digestive and immune health.
      Various aspects related to GOS such as types and functions of functional food
      constituents with special reference to GOS, their role as prebiotics, and
      enhanced industrial production through microbial intervention are dealt in this
      review.

PMID- 22417366
TI  - Potential risks resulting from fruit/vegetable-drug interactions: effects on drug
      metabolizing enzymes and drug transporters.
AB  - It has been well established that complex mixtures of phytochemicals in fruits
      and vegetables can be beneficial for human health. Moreover, it is becoming
      increasingly apparent that phytochemicals can influence the pharmacological
      activity of drugs by modifying their absorption characteristics through
      interactions with drug transporters as well as drug-metabolizing enzyme systems.
      Such effects are more likely to occur in the intestine and liver, where high
      concentrations of phytochemicals may occur. Alterations in cytochrome P450 and
      other enzyme activities may influence the fate of drugs subject to extensive
      first-pass metabolism. Although numerous studies of nutrient-drug interactions
      have been published and systematic reviews and meta-analyses of these studies are
      available, no generalizations on the effect of nutrient-drug interactions on drug
      bioavailability are currently available. Several publications have highlighted
      the unintended consequences of the combined use of nutrients and drugs. Many
      phytochemicals have been shown to have pharmacokinetic interactions with drugs.
      The present review is limited to commonly consumed fruits and vegetables with
      significant beneficial effects as nutrients and components in folk medicine.
      Here, we discuss the phytochemistry and pharmacokinetic interactions of the
      following fruit and vegetables: grapefruit, orange, tangerine, grapes, cranberry,
      pomegranate, mango, guava, black raspberry, black mulberry, apple, broccoli,
      cauliflower, watercress, spinach, tomato, carrot, and avocado. We conclude that
      our knowledge of the potential risk of nutrient-drug interactions is still
      limited. Therefore, efforts to elucidate potential risks resulting from food-drug
      interactions should be intensified in order to prevent undesired and harmful
      clinical consequences.

PMID- 22417367
TI  - Shelf life study of fresh celery (Apium graveolens L.) grown under different
      nitrogen fertilization treatments.
AB  - Nitrogen fertilization is useful for obtaining higher growth and quality of
      productions, and the use of nitrogen fertilization is widespread. To evaluate the
      influence of nitrogen-rich fertilizers on quality characteristics of celery,
      shelf life tests of celery grown with 2 levels of nitrogen and 2 different
      nitrogen fertilizers were performed. The treatments of the celery samples were
      identified as follows: T1, mineral nitrogen (80 kg ha(-1)); T2, mineral nitrogen
      (120 kg ha(-1)); T3, organic nitrogen (80 kg ha(-1)); T4, organic nitrogen (120
      kg ha(-1)); R4, residual organic nitrogen (120 kg ha(-1)); and C, untreated
      control. Celery plants were selected and packaged in either of the following 2
      plastic films: antifog polyolefin (AFP) film or microperforated polypropylene
      (MPP) film. The nitrate contents, weight loss, hardness, changes in color
      parameters, and total phenols were studied for both packaging types during
      storage. The results demonstrated that celery fertilized with organic nitrogen
      and packaged in AFP film reached a shelf life of 37 d. The control sample
      packaged in MPP film was not marketable after 20 d, but the same untreated sample
      packaged in AFP film reached a shelf life of 30 d.

PMID- 22417368
TI  - Effect of dietary vitamin E supplementation and refrigerated storage on quality
      of rainbow trout fillets.
AB  - Rainbow trout were fed a low vitamin E (200 mg/kg; LVE) or a high vitamin E (5000
      mg/kg; HVE) diet for 9 wk to characterize the effect of vitamin E supplementation
      at 5000 mg/kg on fillet quality. Fish were sampled at 2, 3, 4, 5, 7, and 9 wk of
      the trial. Fillets were stored at 2  degrees C for 0, 7, and 14 d, and analyzed
      for pH, psychrotrophic counts, color, cook yield, shear force, crude fat and
      moisture content, alpha-tocopherol, fatty acid composition, and lipid oxidation.
      There was a significant feeding duration by fillet storage time interaction for
      psychrotrophic counts, crude fat content, cook yield, and shear force. Fillet L*
      value was not affected by diet, feeding duration or storage time. Fillet a* was
      lowest at 14-d storage, and b* values increased with fillet storage time. High
      vitamin E diet increased fillet alpha-tocopherol from 33 to 155 mg/kg. High
      vitamin E decreased palmitic acid and increased linoleic acid and omega-6 fatty
      acids. Feeding through 9 wk increased the relative proportions of unsaturated,
      polyunsaturated, and omega-3 fatty acids, and decreased saturated and omega-6
      fatty acids. At 0-d storage, HVE diet did not affect thiobarbituric acid-reactive
      substances (TBARS) at any sampling week, and fasted fish generated fewer TBARS
      compared to non-fasted fish.

PMID- 22417369
TI  - Potassium acetate and potassium lactate enhance the microbiological and physical
      properties of marinated catfish fillets.
AB  - Sodium or potassium salts such as lactate and acetate can be used to inhibit the
      growth of spoilage bacteria and food-borne pathogens, and thereby prolong the
      shelf-life of refrigerated seafood. However, minimal information is available
      regarding the combined effects of potassium salts (acetate and lactate) with an
      agglomerated phosphate blend on the quality and safety of refrigerated catfish
      fillets. The objective of this study was to determine the microbiological and
      quality characteristics of marinated catfish fillets treated with organic acid
      salts. Catfish fillets were vacuum-tumbled with a brine solution with and without
      the added organic acid salts, at 10% over initial, raw weight prior to tray
      packing and storage at 4  degrees C for 14 d. Fillets were evaluated for yields,
      color, pH, tenderness, consumer acceptability, and shelf-life. No differences (P
      > 0.05) existed among the treated and untreated fillets with regards to solution
      pick-up and pH, but all treated fillets increased (P < 0.05) cooking yields and
      Intl. Commission on Illumination (CIE) a* values, and decreased (P < 0.05) CIE L*
      and b* values in the catfish fillets when compared to the untreated fillets. The
      fillets treated with a combination of potassium acetate and potassium lactate had
      lower (P < 0.05) psychrotrophic plate counts and lower spoilage scores than the
      control treatments on days 7, 10, and 14. In addition, consumers preferred (P <
      0.05) treated catfish fillets (fried) with respect to appearance, flavor, and
      overall acceptability over the negative control. In conclusion, the combination
      of potassium acetate and potassium lactate enhanced sensory quality and extended
      the shelf-life of refrigerated catfish fillets.

PMID- 22417370
TI  - Effects of perimortem stress on farmed Atlantic cod product quality: a baseline
      study.
AB  - The potential effects of handling stress on the product quality of farmed
      Atlantic cod were studied in a controlled experiment (fish anesthetized with
      metomidate or isoeugenol, or subjected to stress by chasing for 30 min). For
      comparison, stress and fillet quality was also studied for commercially
      slaughtered farmed cod (fish sampled from waiting cage, after pumping and
      stunning with carbon dioxide, and after bleeding and chilling). Baseline values
      for stress-related parameters (blood chemistry, muscle high-energy phosphates and
      inosine monophospate, initial pH, muscle twitches, and rigor mortis) of rested
      Atlantic cod have been established. Since our stress bout showed that this
      species was not easily excitable, we were less convinced that we actually did
      study the other extreme, namely, exhausted fish. Nevertheless, the present data
      from the commercial slaughter of cod suggested that our stress bout was of
      adequate magnitude to represent potential poor handling routines. Our results
      consistently showed largely no differences between treatments, and that
      perimortem handling stress did not cause inferior flesh quality. This suggested
      that farmed cod can be processed with little risk of reducing product quality
      (quality index, fillet water content, water-holding capacity, ultimate pH,
      adenosine triphosphate-related degradation products and K-value, skin and fillet
      color, water and salt-soluble proteins, hardness, and gaping). For better
      maintenance of skin appearance after storage, the importance of storing the
      gutted cod on the belly, avoiding direct contact between skin and crushed ice, is
      demonstrated.

PMID- 22417371
TI  - Mineral oil-chitosan emulsion coatings affect quality and shelf-life of coated
      eggs during refrigerated and room temperature storage.
AB  - Effects of mineral oil (MO) and 4 emulsions (prepared with different emulsifier
      types) of MO and chitosan solution (CH) at a fixed ratio of MO:CH = 25:75 as
      coating materials in preserving the internal quality of eggs were evaluated
      during 5 wk at 25  degrees C and 20 wk at 4  degrees C. Generally, as storage
      time increased, Haugh unit and yolk index values decreased whereas weight loss
      increased. However, MO and/or 4 emulsion coatings minimized the weight loss
      (<1.5%) and preserved the albumen and yolk quality of eggs (with the final B
      grade) for at least 3 wk longer than those observed for noncoated eggs at 25 
      degrees C. At 4  degrees C, all coated eggs changed from AA to A grade after 5 wk
      and they maintained this grade for 10 wk (5 wk longer than that of noncoated
      eggs). Although refrigeration (4  degrees C) alone could maintain the B grade of
      noncoated eggs for up to 20 wk, coating treatments were necessary to keep the
      weight loss below 2%. Compared with 4  degrees C, the increasing weight loss
      showed stronger negative correlation (P < 0.01) with the decreasing Haugh unit (
      0.46 to -0.89) and yolk index (-0.36 to -0.89) at 25  degrees C. The emulsifier
      type used in this study generally did not affect the internal quality of eggs.
      Salmonella spp. detection was negative for all coated and noncoated eggs. This
      study demonstrated that MO and MO:CH emulsion coatings preserved the internal
      quality, prolonged the shelf-life, and minimized weight loss (<2%) of eggs.

PMID- 22417372
TI  - Inhibition of matrix metalloproteinase activities and tightening of tight
      junctions by diallyl disulfide in AGS human gastric carcinoma cells.
AB  - The effect of diallyl disulfide (DADS), a major component of an oil-soluble allyl
      sulfide garlic (Allium sativum) derivative, on the correlation between anti
      invasive activity and tightening of tight junctions (TJs) was investigated in
      human gastric adenocarcinoma AGS cells. Our data indicated that the inhibitory
      effects of DADS on cell motility and invasiveness were found to be associated
      with increased tightness of the TJs, which was demonstrated by an increase in
      transepithelial electrical resistance. Activities of matrix metalloprotease (MMP)
      2 and -9 in AGS cells were dose-dependently inhibited by treatment with DADS, and
      this was also correlated with a decrease in expression of their mRNA and
      proteins; however, tissue inhibitor of metalloproteinase (TIMP)-1 and -2 mRNA
      levels and proteins were increased. Additionally, immunoblotting results
      indicated that DADS repressed the levels of claudin proteins (claudin-2, -3, and 
      4), major components of TJs that play key roles in control and selectivity of
      paracellular transport. Although further studies are needed, these results
      suggest that DADS treatment may inhibit tumor cell motility and invasion and,
      therefore, act as a dietary source to decrease the risk of cancer metastasis.

PMID- 22417373
TI  - Prediction of effect of natural antioxidant compounds on hazelnut oil oxidation
      by adaptive neuro-fuzzy inference system and artificial neural network.
AB  - In this study, natural compounds including gallic acid, ellagic acid, quercetin,
      beta-carotene, and retinol were used as antioxidant agents in order to prevent
      and decrease oxidation in hazelnut oil. Quercetin showed the strongest
      antioxidative effect among the antioxidative agents, during storage. The accuracy
      of adaptive neuro-fuzzy inference system (ANFIS) and artificial neural network
      (ANN) models was studied to estimate the oil samples' peroxide value (PV), free
      fatty acid (FFA), and iodine values (IV). The root mean square error (RMSE), mean
      absolute error (MAE), and determination coefficient (R(2)) statistics were used
      to evaluate the models' accuracy. Comparison of the models showed that the ANFIS
      model performed better than the ANN and multiple linear regressions (MLR) models
      for estimating the PV, FFA, and IV. The values of R(2) and RMSE were found to be
      0.9966 and 2.51, 0.6269 and 88.55, 0.5120 and 101.8 for the ANFIS, ANN, and MLR
      models for PV in testing period, respectively. The MLR was found to be
      insufficient for estimating various properties of the oil samples.

PMID- 22417374
TI  - The effects of season and sex in the metal levels of mature common cuttlefish
      (Sepia officinalis) in Mersin Bay, Northeastern Mediterranean.
AB  - The effects of sex and season on metal levels of the mantle of the common
      cuttlefish that was caught from Mersin Bay were evaluated. The annual range of
      mantle length (ML), total length (TL), and weight of common cuttlefish specimens
      were 110 to 183 mm, 380 to 581 mm, and 150.24 to 477.13 g, respectively. The
      annual range of metal levels in the mantle tissue of common cuttlefish were: 2.34
      to 3.89 MUg Cd g(-1), 0.30 to 0.63 MUg Cr g(-1), 0.15 to 0.54 MUg Pb g(-1), 2.35
      to 14.90 MUg Cu g(-1), 23.22 to 51.88 MUg Zn g(-1), and 5.12 to 10.65 MUg Fe g(
      1). Cu levels of females were significantly higher (P < 0.05) than those found in
      male throughout all the seasons while Pb levels were lower (P < 0.05) in males
      than females. Cr levels in the mantle tissue of cuttlefish did not change
      throughout the seasons. On the contrary, Cd, Pb, Cu, Zn, and Fe levels in the
      mantle tissue of cuttlefish changed throughout all the seasons. The highest Cd,
      Zn, and Fe levels were obtained in spring while the highest Cu levels were
      obtained in autumn. It was also found out that this species was rich in terms of
      metal levels, particularly, Cd, Cu, Zn, and Fe. It was found out that the mantle
      tissue of the common cuttlefish, Sepia officinalis, which was caught from Mersin
      Bay, was contaminated with Cd in all the seasons.

PMID- 22417375
TI  - Dietary taurine reduces zinc-induced toxicity in male Wistar rats.
AB  - Taurine is an agent for treating the heavy metal intoxication and presence of
      metals such as zinc, copper, and iron may have a role in heavy metal toxicity, a
      study was undertaken to investigate the effect of taurine on the toxicity of zinc
      in male Wistar rats. The rats were divided into 8 groups and fed different diets
      with or without supplement of 5% taurine and 150 to 600 ppm zinc for 2 mo. It was
      found that the body weight of rats, the ratios of liver and kidney weight to body
      weight, and the level of glutathione in the liver were decreased with increasing
      the dose of zinc. The levels of zinc in the liver, kidney, and plasma, the levels
      of malondialdehyde in the plasma, the levels of thiobarbiture acid-reactive
      substances in the liver, the activities of aspartate transaminase, alanine
      transaminase in the plasma, the levels of blood urea nitrogen and creatinine in
      the plasma of rats were increased with the increasing dose of zinc. Hence,
      symptoms of zinc toxicity in rats included loss of body weight, hepatotoxicity,
      and nephrotoxicity. However, these toxic effects of zinc were significantly
      reduced when the rats fed diet with supplement of taurine. Furthermore, the level
      of zinc in the feces of rats treated with taurine and zinc was higher than that
      of rats treated with zinc alone. It indicated that taurine thereby leading to a
      decreased absorption of dietary zinc and promoted excretion.

PMID- 22417376
TI  - Occurrence of Aspergillus spp. and aflatoxin B1 in Malaysian foods used for human
      consumption.
AB  - Malaysian population widely consumes the cereal-based foods, oilseeds, nuts, and
      spices in their daily diet. Mycotoxigenic fungi are well known to invade food
      products under storage conditions and produce mycotoxins that have threat to
      human and animal health. Therefore, determining toxigenic fungi and aflatoxin
      B(1) (AFB1) in foods used for human consumption is of prime importance to develop
      suitable management strategies and to minimize risk. Ninety-five food products
      marketed in Penang, Malaysia were randomly collected from different supermarkets
      and were analyzed for presence of Aspergillus spp. by agar plate assay and AFB1
      by enzyme-linked immunosorbent assay (ELISA). A. flavus was the dominant fungi in
      all foods followed by A. niger. Fifty-five A. flavus strains were tested for
      their ability to produce aflatoxins on rice grain substrate. Thirty-six (65.4%)
      strains out of 55 produced AFB1 ranging from 1700 to 4400 MUg/kg and 17 strains
      (31%) produced AFB2 ranging from 620 to 1670 MUg/kg. Natural occurrence of AFB1
      could be detected in 72.6% food products ranging from 0.54 to 15.33 MUg/kg with a
      mean of 1.95 MUg/kg. Maximum AFB1 levels were detected in peanut products ranging
      from 1.47 to 15.33 MUg/kg. AFB1 levels detected in all food products were below
      the Malaysian permissible limits (<35 MUg/kg). Aspergillus spp. and AFB1 was not
      detected in any cookies tested. Although this survey was not comprehensive, it
      provides valuable information on aflatoxin levels in foods marketed in Malaysia.

PMID- 22417380
TI  - Molecular characterization and increased expression of the Nile tilapia,
      Oreochromis niloticus (L.), T-cell receptor beta chain in response to
      Streptococcus agalactiae infection.
AB  - The complete cDNA sequence of the Nile tilapia T-cell receptor (TCR) beta chain
      was cloned using 5' RACE. The full-length, 1263-bp cDNA contained a 942-bp open
      reading frame (ORF) encoding a 314-amino-acid protein. Sequence analyses revealed
      that the Nile tilapia TCR beta chain contains four conserved cysteine residues
      involved in the formation of disulphide bridges and a conserved amino acid motif
      believed to be important for assembly and signalling of the TCR alphabeta/CD3
      complex, both of which are normally found in the TCR beta chain of other
      vertebrates. As detected using semi-quantitative and quantitative RT-PCR, the
      highest expression level of TCR beta was detected in the thymus. Interestingly,
      Streptococcus agalactiae significantly induced the up-regulation of the TCR beta
      chain, and the strongest up-regulation was detected in the brain and peripheral
      blood leucocytes (PBLs). In in vitro experiments, concanavalin A and Aeromonas
      hydrophila were found to significantly increase the expression of the TCR beta
      chain in PBLs after 48 h (P < 0.01) and 72 h (P < 0.05), respectively.
      Furthermore, real-time PCR analysis showed that intraperitoneal injection (IP) of
      10(7) cfu mL(-1) of S. agalactiae could induce TCR beta expression that was
      greater than the expression observed following administration of 10(9) cfu mL(
      1). The presence of the TCR beta chain in fish detected in this study suggests
      the presence of T-cell populations that have been found in higher vertebrates,
      which may play a crucial functional role in the response to fish pathogens.

PMID- 22417381
TI  - A virtual-reality subtotal tonsillectomy simulator.
AB  - OBJECTIVES: To develop a virtual-reality subtotal tonsillectomy simulation for
      surgical training. MATERIALS AND METHODS: Computer models of a male patient's
      head and throat, and the surgical instrument, were created. These models were
      combined with custom-built simulation software. Recently developed tissue
      simulation technology that exploits recent developments in programmable graphics
      processing units was used to model tonsillar tissue in a way that allows surgical
      interaction whilst providing accurate tactile feedback. Current real-time
      rendering techniques were used to provide realistic visuals. Iterative
      refinements were made to the simulation, and in particular the tissue simulation,
      in consultation with relevantly experienced surgeons. RESULTS: We have used newly
      developed tissue simulation technology to developed a novel virtual-reality
      subtotal tonsillectomy simulation for surgical training, the first of its kind.
      CONCLUSION: Early feedback suggests that this simulator can help surgeons to
      rapidly acquire subtotal tonsillectomy surgical skills in a risk-free and
      realistic virtual environment.

PMID- 22417383
TI  - Graphene oxide based recyclable dehydrogenation of ammonia borane within a hybrid
      nanostructure.
AB  - The recyclable dehydrogenation of ammonia borane (AB) is achievable within a
      graphene oxide (GO)-based hybrid nanostructure, in which a combined modification
      strategy of acid activation and nanoconfinement by GO allows AB to release more
      than 2 equiv of pure H(2) at temperatures below 100  degrees C. This process
      yields polyborazylene (PB) as a single product and, thus, promotes the chemical
      regeneration of AB via reaction of PB with hydrazine in liquid ammonia.

PMID- 22417382
TI  - Short-term effects of humidification devices on respiratory pattern and arterial
      blood gases during noninvasive ventilation.
AB  - BACKGROUND: The impact of humidification devices on ventilatory and arterial
      blood gases parameters during noninvasive ventilation (NIV) remains
      controversial. The aim of the study was to compare the short-term impact of heat
      and moisture exchangers (HMEs) and heated humidifiers (HHs)  during NIV for
      either hypercapnic or hypoxemic acute respiratory failure. METHODS: Consecutive
      subjects receiving NIV were successively treated with HME and HH in randomized
      order for 30 min each. At the end of each period, arterial blood gases were
      measured and ventilatory parameters were  recorded. RESULTS: Eighty-one subjects
      were enrolled, of whom 52 were hypercapnic (with or without acidosis) and 29
      hypoxemic. Minute ventilation was greater with the HME, in comparison with the HH
      (15 [12-18] vs 12 [10-16] median [interquartile range], P < .001), while 
      P(aCO(2)) was increased when using HME, indicating a dead space effect. This
      effect was observed in all subjects, but was more pronounced in hypercapnic
      subjects (P(aCO(2)) 62 +/- 17 mm Hg with HME vs 57 +/- 14 with HH, P < .001). In 
      a subgroup of 19 subjects with respiratory acidosis, alveolar hypoventilation
      improved only with the HH. The amplitude of the dead space impact was a function
      of the degree of hypercapnia. CONCLUSIONS: Use of an HME decreased CO(2)
      elimination during NIV, despite increased minute  ventilation, especially in
      hypercapnic subjects.

PMID- 22417384
TI  - Experimental "microcultures" in young children: identifying biographic,
      cognitive, and social predictors of information transmission.
AB  - In one of the first open diffusion experiments with young children, a tool-use
      task that afforded multiple methods to extract an enclosed reward and a child
      model habitually using one of these methods were introduced into different
      playgroups. Eighty-eight children, ranging in age from 2 years 8 months to 4
      years 5 months, participated. Measures were taken of how alternative methods and
      success in extracting rewards spread across the different groups. Additionally,
      the biographic, social, cognitive, and temperamental predictors of social
      learning were investigated. Variations in social learning were related to age,
      popularity, dominance, impulsivity, and shyness, while other factors such as sex,
      theory of mind, verbal ability, and even imitativeness showed little association
      with variance in children's information acquisition.

PMID- 22417385
TI  - ALDH1A1 is a marker of astrocytic differentiation during brain development and
      correlates with better survival in glioblastoma patients.
AB  - Glioblastoma is the most common malignant brain tumor and patients usually
      succumb to their disease within 2 years. Aldehyde dehydrogenase 1A1 (ALDH1A1) has
      been suggested as a marker for cancer stem cells that is associated with poor
      prognosis in human gliomas. However, little is known about the expression and the
      function of ALDH1A1 in early stages of brain development. We analyzed ALDH1A1
      expression in developing and mature central nervous system (CNS) as well as in 93
      cases of primary glioblastomas. Surprisingly, ALDH1A1 was absent in the stem cell
      niches at varying stages of CNS development, but strong ALDH1A1 expression was
      observed in mature astrocytes coexpressing GFAP and S100. There were 92 out of 93
      glioblastomas (99%) that showed ALDH1A1 protein expression in up to 49% of tumor
      cells. The majority of these cells co-expressed GFAP, but not established stem
      cell markers such as Nestin, OLIG2 or SOX2. Finally, strong expression of ALDH1A1
      correlated with a significantly better survival of the patients and proved to be
      an independent prognostic marker in our series (P < 0.01). In contrast to other
      published data, we therefore provide evidence for ALDH1A1 as a marker of
      astrocytic differentiation during brain development and of better prognosis in
      patients suffering from primary glioblastoma.

PMID- 22417386
TI  - Severity of obstructive sleep apnea in patients with and without cardiovascular
      related diseases.
AB  - BACKGROUND: Previous studies have often investigated the association of
      obstructive sleep apnea (OSA) with cardiovascular morbidity and mortality, but
      the possibility of reverse causation has not been clearly defined. OBJECTIVE: To
      examine if the presence of any of the cardiovascular-related  diseases, including
      hypertension, diabetes mellitus, coronary artery disease, and/or cerebrovascular
      disease, correlates with more severe OSA. METHODS: This was a retrospective study
      where all patients age >= 18 years referred to our sleep laboratory for suspected
      OSA were included. The  data from the full-night baseline and split-night
      polysomnographic reports were reviewed. Data were then evaluated by logistic
      regression analysis to compare between 2 groups, the severity of OSA (respiratory
      disturbance index [RDI] < 15 vs RDI >= 15, and RDI < 5 vs RDI >= 5), other 
      polysomnographic variables and daytime sleepiness score (Epworth Sleepiness Scale
      [ESS] score < 10 and >= 10). RESULTS: 190 patients were analyzed. The patients
      with any of the cardiovascular-related diseases were noted to have more severe
      sleep apnea (RDI >= 15), with an adjusted odds  ratio of 3.24. Sleep efficiency
      >= 90% and mean oxygen saturation >= 95% were observed less commonly in the
      patients with any of the cardiovascular-related diseases (adjusted odds ratios of
      0.45 and 0.36, respectively). There was no statistically significant difference
      in ESS score. CONCLUSIONS: Patients with any of the cardiovascular-related
      diseases are at a higher risk of having moderate to severe OSA without
      significant increase in daytime sleepiness. Therefore, we suggest that patients
      with any of the cardiovascular-related diseases should be screened for OSA, even
      if they are  asymptomatic.

PMID- 22417387
TI  - Hydrogen cyanide synthesis and antifungal activity of the biocontrol strain 
      Pseudomonas fluorescens  In5 from Greenland is highly dependent on growth medium.
AB  - Hydrogen cyanide (HCN) is a secondary metabolite produced by many antagonistic 
      Pseudomonas  species. In the present study, the gene cluster encoding HCN
      synthesis in a newly isolated  Pseudomonas fluorescens  strain, In5, from South
      Greenland was investigated. Sequence analysis showed that the Greenlandic hcn
      gene cluster comprises a novel hcn cluster. Transposon mutagenesis of strain In5
      resulted in mutants In5-2E1 and In5-1H7 with no production of HCN, and mutant In5
      6B9 with reduced HCN synthesis. In mutant In5-2E1, the transposon was inserted
      into the hcnC gene; in mutant In5-1H7, the Tn5 insertion was found in a region
      upstream of a putative malate:quinone oxidoreductase gene (mqo); and in mutant
      In5-6B9, the transposon disrupted a probable enoyl-CoA hydratase/isomerase gene.
      In vitro inhibition experiments with In5 (wild type) and In5-2E1 (mutant) showed
      that in nitrogen-rich Luria-Bertani medium, strain In5 but not the hcn mutant In5
      2E1 produced HCN and inhibited the growth of hyphae of  Rhizoctonia solani  and 
      Pythium aphanidermatum . In contrast, when cultivating the strains in the
      carbohydrate-rich potato dextrose medium, neither of the strains produced any
      HCN, and thus, they were unable to inhibit hyphal growth of fungi. These
      experiments strongly indicate that the synthesis of HCN is highly dependent on
      the growth medium used.

PMID- 22417388
TI  - [Presence and representation of older people in prime-time television
      advertising: the Spanish case].
AB  - INTRODUCTION: The demographic shift towards aging population generates a series
      of socioeconomic and cultural changes that are beginning to transform the role
      and public image of older people. The elderly have become one of the market
      segments with a greater future. This fact has attracted little scientific
      interest in the field of advertising communication and for this reason there is
      little research that is actually looking into this Spain. This research examines
      the use that is made of the image of the elderly in the television advertising in
      Spain, looking at the differences between the advertisement dedicated to the
      targeting people over 65, and those that are not directed at the elderly, but use
      older people in their content as actors or main characters in the advertisement.
      MATERIAL AND METHODS: A content analysis study was conducted on a sample of 2,065
      spots obtained from prime time slots (from 20:30 to 22:30 p.m.) from the five
      major Spanish television channels (TVE 1, La 2, Tele 5, Antena 3 and Cuatro). Two
      independent judges coded all the advertisements. The reliability coefficient
      between judges was 0.91. RESULTS AND CONCLUSIONS: In general, older people,
      particularly women, are not very often shown in Spanish advertising. Their
      presence is much stronger and visible in campaigns which aim their communication
      strategy at different age groups. In those cases, advertising presents the
      elderly with a stereotyped, self-interested and traditional image.

PMID- 22417389
TI  - Polycyclic aromatic and aliphatic hydrocarbons pollution at the coast of Aliaga
      (Turkey) ship recycling zone.
AB  - Aliaga Bay is one of the most important maritime zones of Turkey where shipping
      activity, shipbreaking industry, steel works and petrochemical complexes exist
      together. Polycyclic aromatic hydrocarbons (PAHs) and aliphatic hydrocarbons in
      sediment of the Aliaga Bay were investigated to evaluate an environmental risk
      assessment from PAHs contamination in 2009-2010. Aliphatic and PAHs diagnostic
      ratios were showed to be mainly petroleum-originated and pyrolitic
      contaminations, respectively. The TEL/PEL analysis suggests that Aliaga sediments
      were likely to be contaminated by acutely toxic PAH compounds.

PMID- 22417390
TI  - Grounded or submerged bulk carrier: the potential for leaching of coal trace
      elements to seawater.
AB  - This study investigates the potential for leaching of coal trace elements to
      seawater from a grounded bulk carrier. The coal type and ecological scenario was
      based on the grounding of the "Shen Neng" (April 2010) at Douglas Shoal located
      within the Great Barrier Reef (Queensland, Australia). The area is of high
      ecological value and the Queensland Water Quality Guidelines (2009) provided
      threshold limits to interpret potential impacts. Coal contains many trace
      elements that are of major and moderate concern to human health and the
      environment although many of these concerns are only realised when coal is
      combusted. However, "unburnt" coal contains trace elements that may be leached to
      natural waterways and few studies have investigated the potential ecological
      impact of such an occurrence. For example, coal maritime transport has increased
      by almost 35% over the last five reported years (Jaffrennou et al., 2007) and as
      a result there is an increased inherent risk of bulk carrier accidents. Upon
      grounding or becoming submerged, coal within a bulk carrier may become saturated
      with seawater and potentially leach trace elements to the environment and impact
      on water quality and ecological resilience. The worst case scenario is the
      breakup of a bulk carrier and dispersal of cargo to the seafloor.

PMID- 22417391
TI  - Stability and structure of long intramolecular G-quadruplexes.
AB  - G-quadruplexes are formed from guanine-rich sequences of DNA and RNA. They
      consist of stacks of square arrangements of guanines called G-quartets.
      Increasing evidence suggests that these structures are involved in cellular
      processes such as transcription or translation. Knowing their structure and their
      stability in vitro should help to predict their formation in vivo and to
      understand their biological functions. Many studies have been performed on
      isolated G-quadruplexes, but little attention has been given to their
      interactions. Here, we present non-denaturing gel electrophoresis, UV melting,
      and circular dichroism data obtained for long sequences of DNA which are capable
      of forming two simultaneous G-quadruplexes, namely,
      d(TG(3)T(3)G(3)T(3)G(3)T(3)G(3)T(n)G(3)T(3)G(3)T(3)G(3)T(3)G(3)T), with n varying
      from one to seven. These sequences can form up to two separate G-quadruplexes. We
      also study mutated versions of these sequences designed to form one G-quadruplex
      at specific positions on the strand. Comparing results from the original
      sequences and their mutated versions, we show that for the former different
      folded states coexist: either with six stacked G-quartets or only three, in
      various combinations. Which ones are favored depends on n. Moreover, for n
      greater than three, the thermodynamic stability stays constant, contrary to an
      expected decrease in stability if the six G-quartets were stacked together in a
      single structure. This result agrees with a beads-on-a-string folding model for
      long sequences of G-quadruplexes, where two adjacent G-quadruplexes fold
      independently.

PMID- 22417392
TI  - Post-biopsy arteriovenous fistula in transplant kidney: treatment with
      superselective transcatheter embolisation.
AB  - PURPOSE: To evaluate the technical success and therapeutic effect of
      superselective embolisation of arteriovenous fistulas in renal allografts.
      MATERIALS AND METHODS: Between 2000 and 2009, 20 patients underwent angiography
      of 24 AV fistulas (AVF) following percutanous biopsy of the transplanted kidney.
      Indications for angiography were the diagnosis of AVF by ultrasound and in
      addition persistent or worsening transplant renal function, or haematuria.
      Superselective catheterisation of the fistula was performed with a coaxial
      microcatheter and microcoils were used to occlude the fistula. To assess the
      short-term effect of embolisation, serum creatinine values were evaluated before
      embolisation, in the first week after embolisation and after a period of minimum
      42 days after the procedure. RESULTS: Angiography identified a single AVF in 16
      patients and two AVFs in 4 patients. In 19 patients, successful embolisation was
      achieved without complications. In one patient, a second session was needed to
      embolise the AVF completely. The mean serum creatinine level of all patients with
      embolisation dropped significantly (p=0.0014) from 4.4 mg/dl (range: 1.4-11.6
      mg/dl, standard deviation: 3.0) before embolisation to 2.7 mg/dl after
      embolisation (range: 1.0-7.0mg, standard deviation: 1.8). No patient showed an
      increase in serum creatinine. Long-term outcomes of the renal allograft revealed
      a well-functioning allograft in 19/20 patients. One patient returned to
      haemodialysis due to acute rejection. CONCLUSION: Superselective transcatheter
      embolisation is a safe and highly effective treatment for AVFs in renal
      allografts. Renal function was improved in the majority of patients.

PMID- 22417393
TI  - The role of second-look ultrasound of BIRADS-3 mammary lesions detected by breast
      MR imaging.
AB  - OBJECTIVE: To asses the value of second-look ultrasound (US) for identifying
      BIRADS 3 (Breast Imaging Reporting Data System) mammary lesions detected by
      breast Magnetic Resonance imaging (MRI). MATERIALS AND METHODS: From April 2008
      to May 2009 330 breast MRI were performed of which 60 patients are classified as
      BIRADS 3. 84 lesions underwent second-look US and percutaneous vacuum biopsy
      Vacora system US-guided. STATISTICAL ANALYSIS: lesions were stratified into two
      groups: visible on US (Group 1) and not visible on US (Group 2). The clinical
      impact of second-look US was studied in terms of negative predictive value (NPV).
      RESULTS: The positive predictive value (PPV) of category 3 BIRADS MRI was found
      to be 89%. Second look-US results detected lesions in 51% of the MRI enhancing
      lesions. The second look-US showed a NPV of 97%. The NPV of second look-US was
      significantly greater than the NPV of MRI BIRADS 3 (97% vs 89%, p<0.05). The
      logistic regression analysis showed a higher number of malignant lesions in group
      1 than in group 2 (7vs 2, OR 3.7, p<0.05). CONCLUSIONS: The second-look US
      permitted the correct management of subcentimetric MRI BIRADS 3 lesions not
      visible with conventional imaging tecniques.

PMID- 22417395
TI  - Correlating the structure and composition of ionic liquids with their toxicity on
      Vibrio fischeri: A systematic study.
AB  - A systematic screening of the toxicity of ionic liquids (IL) towards Vibrio
      fischeri, a bioluminescent marine bacteria generally used in ecotoxicological
      bioassays, was carried out. The objectives of this work were to find hydrophilic
      or hydrophobic low toxicity IL and to investigate structure-toxicity relationship
      of IL. Toxicity of 54 IL to V. fischeri have been measured, some referring to new
      IL based on quinuclidinol or tropinol and some to generic IL (i.e., imidazolium,
      pyridinium, pyrrolidinium or piperidinium). For 47 of them, toxicity values have
      not been reported elsewhere. Water-soluble IL containing hydrophilic anions
      halide, thiocyanate, dicyanamide, trifluoromethansulfonate were studied. Some IL
      were found to exhibit very low toxicity towards V. fisheri. Hydrophobic IL based
      on bis(trifluoromethanesulfonyl)imide, tetrafluoroborate tetraphenylborate and
      tetracyanoborate were also studied. Toxicity was measured in a consistent way
      starting from aqueous solutions saturated with IL. The least toxic hydrophobic IL
      found in this study was [EMIM][B(CN)(4)]. A multifactorial analysis was found to
      be convenient for finding relevant structure parameters influencing the toxicity
      of IL. From this analysis, the planarity of the cation ring appeared to be a
      relevant parameter. Finally, good linear correlations were found when toxicity of
      IL was plotted either against the number of aliphatic carbons surrounding a
      pyridinium cation or the total number of carbons of a cation.

PMID- 22417394
TI  - Reduction and immobilization of chromate in chromite ore processing residue with
      nanoscale zero-valent iron.
AB  - Chromite ore processing residue (COPR) poses a great environmental and health
      risk with persistent Cr(VI) leaching. To reduce Cr(VI) and subsequently
      immobilize in the solid matrix, COPR was incubated with nanoscale zero-valent
      iron (nZVI) and the Cr(VI) speciation and leachability were studied. Multiple
      complementary analysis methods including leaching tests, X-ray powder
      diffraction, X-ray absorption near edge structure (XANES) spectroscopy, and X-ray
      photoelectron spectroscopy (XPS) were employed to investigate the immobilization
      mechanism. Geochemical PHREEQC model calculation agreed well with our acid
      neutralizing capacity experimental results and confirmed that when pH was lowered
      from 11.7 to 7.0, leachate Cr(VI) concentrations were in the range 358-445mgL(-1)
      which contributed over 90% of dissolved Cr from COPR. Results of alkaline
      digestion, XANES, and XPS demonstrated that incubation COPR with nZVI under water
      content higher than 27% could result in a nearly complete Cr(VI) reduction in
      solids and less than 0.1mgL(-1) Cr(VI) in the TCLP leachate. The results
      indicated that remediation approaches using nZVI to reduce Cr(VI) in COPR should
      be successful with sufficient water content to facilitate electron transfer from
      nZVI to COPR.

PMID- 22417396
TI  - Characterization of surface hydrophobicity of engineered nanoparticles.
AB  - The surface chemistry of nanoparticles, including their hydrophobicity, is a key
      determinant of their fate, transport and toxicity. Engineered NPs often have
      surface coatings that control the surface chemistry of NPs and may dominate the
      effects of the nanoparticle core. Suitable characterization methods for surface
      hydrophobicity at the nano-scale are needed. Three types of methods, surface
      adsorption, affinity coefficient and contact angle, were investigated in this
      study with seven carbon and metal based NPs with and without coatings. The
      adsorption of hydrophobic molecules, Rose Bengal dye and naphthalene, on NPs was
      used as one measure of hydrophobicity and was compared with the relative affinity
      of NPs for octanol or water phases, analogous to the determination of octanol
      water partition coefficients for organic molecules. The sessile drop method was
      adapted for measuring contact angle of a thin film of NPs. Results for these
      three methods were qualitatively in agreement. Aqueous-nC(60) and tetrahydrofuran
      nC(60) were observed to be more hydrophobic than nano-Ag coated with
      polyvinylpyrrolidone or gum arabic, followed by nano-Ag or nano-Au with citrate
      functionalized surfaces. Fullerol was shown to be the least hydrophobic of seven
      NPs tested. The advantages and limitations of each method were also discussed.

PMID- 22417397
TI  - Use of intestinal Pseudomonas aeruginosa in fish to detect the environmental
      pollutant benzo[a]pyrene.
AB  - This study examined the potential of Pseudomonas aeruginosa abundance in the
      intestines of fish as an indicator of exposure to benzo[a]pyrene (BaP). P.
      aeruginosa populations were enumerated in juvenile African catfish (Clarias
      gariepinus) injected intramuscularly three days previous with 0, 10, 30, 40, 50
      or 70mg/kg of BaP. Hepatic EROD and GST activities and biliary fluorescent
      aromatic compounds (FACs) 1-OH BaP, 3-OH BaP, 7,8-D BaP and BaP were quantified
      to investigate agreements between the new indicator and established fish
      biomarkers. The shape of bacterial population (logarithm of colony-forming unit)
      dose-response curve generally matched those of biliary FACs concentrations.
      Conversely, the EROD and GST dose-response curves were generally the mirror
      images of the bacterial population curve. Changes in intestinal P. aeruginosa
      population appear to be an indirect effect of BaP exposure because exposure to 0
      100MUg/ml BaP had no effect on P. aeruginosa populations grown on agar plates
      containing BaP. Using intestinal P. aeruginosa population of fish as a universal
      indicator of BaP pollution in aquatic environments is discussed.Conversely, the
      EROD and GST dose-response curves were generally the mirror images of the
      bacterial population curve.

PMID- 22417398
TI  - CFD modeling of a UV-LED photocatalytic odor abatement process in a continuous
      reactor.
AB  - This paper presents a model study of a UV light-emitting-diode (UV-LED) based
      photocatalytic odor abatement process. It integrated computational fluid dynamics
      (CFD) modeling of the gas flow in the reactor with LED-array radiation field
      calculation and Langmuir-Hinshelwood reaction kinetics. It was applied to
      simulate the photocatalytic degradation of dimethyl sulfide (DMS) in a UV-LED
      reactor based on experimentally determined chemical kinetic parameters. A non
      linear power law relating reaction rate to irradiation intensity was adopted. The
      model could predict the steady state DMS concentration profiles by calculating
      the advection, diffusion and Langmuir-Hinshelwood reaction kinetics. By affecting
      the radiation intensity and uniformity, the position of the LED array relative to
      the catalyst appeared to be a critical parameter determining DMS removal
      efficiency. Too small distances might yield low quantum efficiency and
      consequently poor abatement performance. This study provided an example of LED
      based photocatalytic process modeling and gave insights into the optimization of
      light source design for photocatalytic applications.

PMID- 22417399
TI  - Preparation of ZnO/SiO2 gel composites and their performance of H2S removal at
      room temperature.
AB  - ZnO/SiO(2) gel composites with different active component loading were prepared
      by sol-gel method combined with ambient drying process, followed by thermal
      treatment. The gel composites were characterized by scanning electron microscopy
      (SEM), nitrogen adsorption, X-ray diffraction (XRD), FTIR and X-ray photoelectron
      spectroscopy (XPS), and their performances for H(2)S removal were evaluated by
      dynamic testing at room temperature. The as prepared materials exhibited high
      surface area with multimodal pore size distributions in micropore and mesopore
      region. The porous properties were significantly influenced both by the ZnO
      loading ratio and the treated temperature. The gel composites showed a high
      performance for H(2)S removal, with the highest H(2)S adsorption capacity of
      96.4mg/g for the sample treated at 400 degrees C with 30wt% ZnO. Both
      physisorption and the active phase reactivation governed the H(2)S removal
      process. It needs to optimize the composites' porous structure and active
      component loading amount.

PMID- 22417400
TI  - Heterogeneous activation of peroxymonosulphate by supported ruthenium catalysts
      for phenol degradation in water.
AB  - Activated carbon (AC) and Zeolite Socony Mobil-5 (ZSM5) supported ruthenium oxide
      catalysts were prepared and tested to degrade aqueous phenol in the presence of
      peroxymonosulphate. The physicochemical properties of ruthenium oxide based
      catalysts were characterised by several techniques such as XRD (X-ray
      diffraction), SEM-EDS (scanning electron microscopy-energy dispersive X-ray
      spectroscopy), and N(2) adsorption. It was found that RuO(2)/AC was highly
      effective in heterogeneous activation of peroxymonosulphate to produce sulphate
      radicals, presenting higher reaction rate in phenol degradation compared with
      RuO(2)/ZSM-5. Degradation efficiency of phenol could be achieved at 100% of
      phenol decomposition and 60% of total organic carbon (TOC) removal in 1h at the
      conditions of 50ppm phenol, 0.2g catalyst, 1g Oxone((r)) in 500mL solution at 25
      degrees C using the two catalysts. It was also found that phenol degradation was
      strongly influenced by catalyst loading, phenol concentration, Oxone((r))
      concentration and temperature. Kinetic studies proved that a pseudo first order
      kinetics would fit to phenol decomposition and the activation energies for
      RuO(2)/AC and RuO(2)/ZSM5 were obtained to be 61.4 and 42.2kJ/mol, respectively.

PMID- 22417401
TI  - Activity level of hospital medical inpatients: an observational study.
AB  - OBJECTIVES: To determine the activity level of people admitted for an acute
      hospital medical admission and to describe the location of and people present at
      the activity. DESIGN: Prospective observational behavioral mapping study.
      PARTICIPANTS: 102 patients admitted to general medical wards. INTERVENTION:
      Participants were observed 1min every 10min during a working day from 8.30am to
      4.30pm. OUTCOME MEASURES: Highest level of activity was recorded; location,
      activity and person/s attending the participant. RESULTS: Data from 76
      participants were analyzed; mean age 67 (SD 19) years, 38 (50%) male.
      Participants were observed for 450min. They spent 394 (88%) min in their rooms,
      18 (4%) min in the bathroom and 27 (6%) min off the ward. Of the time in their
      rooms, participants spent a median 315 (IQR 205-398) min lying in bed, 10 (IQR 0
      38) min sitting on or out of bed and 1 (IQR 0-20) min standing or walking.
      Participants spent a median 115 (IQR 70-158) min doing nothing, 80 (IQR 43-160)
      min resting or sleeping and 75 (IQR 40-168) min talking, reading or watching
      television. Participants were alone 280 (IQR 230-340) min and with one person 90
      (IQR 50-130) min. Participants were with staff a median 120 (IQR 73-180) min;
      nurses 35 (IQR 20-60) min, medical staff 10 (IQR 0-18) min and allied health
      staff 10 (IQR 0-20) min. CONCLUSION: People admitted to general medical wards are
      inactive during hospital stay; spending the majority of the working day in their
      rooms, in bed and alone.

PMID- 22417402
TI  - The fatigue and self-care agency levels of the elderly people staying in rest
      homes and the relation between these two conditions.
AB  - This study was carried out to determine the fatigue and self-care levels of the
      elderly and the relation between these two conditions. One hundred forty-two
      individuals at the age of 65 or over were included in the descriptive-analytic
      study. Data were collected using Personal Information Forms to determine socio
      demographic features and social relationships, and the Visual Analog Scale for
      Fatigue (VAS-F) to determine the fatigue status and Exercise of Self-Care Agency
      Scale (ESCA) to measure the self-care agency. The mean age of the elders who
      participated in the survey was 76.15+/-8.61 and their fatigue and energy level
      scores from VAS-F were 5.08+/-2.20 and 3.70+/-1.51 respectively. The value
      obtained from ESCA was 82.68+/-16.39. There is, statistically, a weak negative
      correlation (r=-0.459; p=0.00) between fatigue and energy levels, a weak positive
      correlation (r=0.284; p=0.01) between self-care agency and energy levels, a weak
      negative correlation (r=-0.258; p=0.02) between self-care agency and fatigue
      levels. According to the survey findings, it can be hypothesized that as elders
      living in rest homes, their energy level falls down, they experience moderate
      fatigue and have self-care agency a little more than moderate level, and the lack
      of energy and fatigue they experience affect their self-care agency.

PMID- 22417403
TI  - Mining geriatric assessment data for in-patient fall prediction models and high
      risk subgroups.
AB  - BACKGROUND: Hospital in-patient falls constitute a prominent problem in terms of
      costs and consequences. Geriatric institutions are most often affected, and
      common screening tools cannot predict in-patient falls consistently. Our
      objectives are to derive comprehensible fall risk classification models from a
      large data set of geriatric in-patients' assessment data and to evaluate their
      predictive performance (aim#1), and to identify high-risk subgroups from the data
      (aim#2). METHODS: A data set of n = 5,176 single in-patient episodes covering 1.5
      years of admissions to a geriatric hospital were extracted from the hospital's
      data base and matched with fall incident reports (n = 493). A classification tree
      model was induced using the C4.5 algorithm as well as a logistic regression
      model, and their predictive performance was evaluated. Furthermore, high-risk
      subgroups were identified from extracted classification rules with a support of
      more than 100 instances. RESULTS: The classification tree model showed an overall
      classification accuracy of 66%, with a sensitivity of 55.4%, a specificity of
      67.1%, positive and negative predictive values of 15% resp. 93.5%. Five high-risk
      groups were identified, defined by high age, low Barthel index, cognitive
      impairment, multi-medication and co-morbidity. CONCLUSIONS: Our results show that
      a little more than half of the fallers may be identified correctly by our model,
      but the positive predictive value is too low to be applicable. Non-fallers, on
      the other hand, may be sorted out with the model quite well. The high-risk
      subgroups and the risk factors identified (age, low ADL score, cognitive
      impairment, institutionalization, polypharmacy and co-morbidity) reflect domain
      knowledge and may be used to screen certain subgroups of patients with a high
      risk of falling. Classification models derived from a large data set using data
      mining methods can compete with current dedicated fall risk screening tools, yet
      lack diagnostic precision. High-risk subgroups may be identified automatically
      from existing geriatric assessment data, especially when combined with domain
      knowledge in a hybrid classification model. Further work is necessary to validate
      our approach in a controlled prospective setting.

PMID- 22417404
TI  - Prevalence and factors associated with cryptococcal antigenemia among severely
      immunosuppressed HIV-infected adults in Uganda: a cross-sectional study.
AB  - BACKGROUND: Cryptococcal infection is a common opportunistic infection among
      severely immunosuppressed HIV patients and is associated with high mortality.
      Positive cryptococcal antigenemia is an independent predictor of cryptococcal
      meningitis and death in patients with severe immunosuppression. We evaluated the
      prevalence and factors associated with cryptococcal antigenemia among patients
      with CD4 counts of 100 cells/mm(3) or less in Mulago Hospital, Kampala, Uganda.
      Screening of a targeted group of HIV patients may enable early detection of
      cryptococcal infection and intervention before initiating antiretroviral therapy.
      Factors associated with cryptococcal antigenemia may be used subsequently in
      resource-limited settings in screening for cryptococcal infection, and this data
      may also inform policy for HIV care. METHODS: In this cross-sectional study, HIV
      infected patients aged 18 years and older with CD4 counts of up to 100
      cells/mm(3) were enrolled between December 2009 and March 2010. Data on socio
      demographics, physical examinations and laboratory tests were collected. Factors
      associated with cryptococcal antigenemia were analyzed using multiple logistic
      regression. RESULTS: We enrolled 367 participants and the median CD4 count was 23
      (IQR 9-51) cells/mm(3). Sixty-nine (19%) of the 367 participants had cryptococcal
      antigenemia. Twenty-four patients (6.5%) had cryptococcal meningitis on
      cerebrospinal fluid analysis and three had isolated cryptococcal antigenemia.
      Factors associated with cryptococcal antigenemia included: low body mass index of
      15.4 kg/m2 or less (adjusted odds ratio, AOR = 0.5; 95% CI 0.3-1.0), a CD4(+) T
      cell count of less than 50 cells/mm(3) (AOR = 2.7; 95% CI1.2-6.1), neck pain (AOR
      = 2.3; 95% CI 1.2-4.6), recent diagnosis of HIV infection (AOR = 1.9; 95% CI 1.1
      3.6), and meningeal signs (AOR = 7.9; 95% CI 2.9-22.1). However, at sub-analysis
      of asymptomatic patients, absence of neck pain (AOR = 0.5), photophobia (AOR =
      0.5) and meningeal signs (AOR = 0.1) were protective against cryptococcal
      infection. CONCLUSIONS: Cryptococcal antigenemia is common among severely
      immunosuppressed HIV patients in Mulago Hospital, Kampala, Uganda. Independent
      predictors of positive serum cryptococcal antigenemia were CD4(+) T cell counts
      of less than 50 cells/mm, low body mass index, neck pain, signs of meningeal
      irritation, and a recent diagnosis of HIV infection. Routine screening of this
      category of patients may detect cryptococcosis, and hence provide an opportunity
      for early intervention. Absence of neck pain, photophobia and meningeal signs
      were protective against cryptococcal infection compared with symptomatic
      patients.

PMID- 22417405
TI  - Highly sensitive determination of capsaicin using a carbon paste electrode
      modified with amino-functionalized mesoporous silica.
AB  - Mesoporous silica (MS) and amino-functionalized mesoporous silica (NH(2)-FMS)
      were prepared and characterized using the techniques of transmission electron
      microscopy (TEM) and nitrogen adsorption-desorption. Voltammetry was used to
      investigate the electrochemical behavior of capsaicin at the amino-functionalized
      mesoporous silica, which was modified through carbon paste electrode (NH(2)
      FMS/CPE). NH(2)-FMS/CPE showed better performance for the electrochemical
      oxidation of capsaicin, when compared with bare carbon paste electrode (CPE) and
      mesoporous silica modified carbon paste electrode (MS/CPE). We optimized the
      experimental conditions influencing the determination of capsaicin. Under optimal
      conditions, the oxidation peak current was proportional to capsaicin
      concentration in the range of 0.040-0.40 MUmol L(-1)and 0.40-4.0 MUmol L(-1),
      when the detection limit was 0.020 MUmol L(-1) (S/N=3). The above method was
      successfully applied to determine capsaicin in hot pepper samples, yielding
      satisfactory results. The spiked recoveries were in the range of 93.1-100.7%.

PMID- 22417406
TI  - A theoretical method to determine unstressed off-rate from multiple bond force
      spectroscopy.
AB  - Using dynamic force spectroscopy to measure the kinetic off-rates of
      intermolecular bonds currently requires the isolation of single molecules. This
      requirement arises in part because no tractable analytic method for determining
      kinetic off-rates from the rupture of a large number of bonds under dynamic
      forces is currently available. We introduce a novel method for determining the
      unstressed off-rate from dynamic force spectroscopy experiments involving a large
      number of bonds. Using both the Bell and Dembo models we show that the unstressed
      off-rate calculated using the proposed method is in good agreement with the
      prescribed unstressed off-rate used in Monte-Carlo simulations of multiple bond
      dynamic force spectroscopy experiments given initial number of bonds (50-500) and
      loading rate 10(3)-10(6)pN/s.

PMID- 22417407
TI  - The CDC's Center for Global Health.

PMID- 22417408
TI  - Re: RCP should make an urgent statement against Health and Social Care Bill.

PMID- 22417409
TI  - Metal-on-metal failures--in science, regulation, and policy.

PMID- 22417410
TI  - Failure rates of stemmed metal-on-metal hip replacements: analysis of data from
      the National Joint Registry of England and Wales.
AB  - BACKGROUND: Total hip replacement (THR) is extremely common. Some prostheses
      fail, particularly in younger patients, and need to be revised, most commonly for
      loosening secondary to wear or dislocation. Surgeons have tried to address these
      problems by implanting large diameter metal-on-metal bearing surfaces. Our aim
      was to assess if metal-on-metal bearing surfaces lead to increased implant
      survival compared with other bearing surfaces in stemmed THR and, additionally,
      if larger head sizes result in improved implant survival. METHODS: We analysed
      the National Joint Registry of England and Wales for primary hip replacements
      (402,051, of which 31,171 were stemmed metal-on-metal) undertaken between 2003
      and 2011. Our analysis was with a multivariable flexible parametric survival
      model to estimate the covariate-adjusted cumulative incidence of revision
      adjusting for the competing risk of death. FINDINGS: Metal-on-metal THR failed at
      high rates. Failure was related to head size, with larger heads failing earlier
      (3.2% cumulative incidence of revision [95% CI 2.5-4.1] for 28 mm and 5.1% [4.2
      6.2] for 52 mm head at 5 years in men aged 60 years). 5 year revision rates in
      younger women were 6.1% (5.2-7.2) for 46 mm metal-on-metal compared with 1.6%
      (1.3-2.1) for 28 mm metal-on-polyethylene. By contrast, for ceramic-on-ceramic
      articulations larger head sizes were associated with improved survival (5 year
      revision rate of 3.3% [2.6-4.1] with 28 mm and 2.0% [1.5-2.7] with 40 mm for men
      aged 60 years). INTERPRETATION: Metal-on-metal stemmed articulations give poor
      implant survival compared with other options and should not be implanted. All
      patients with these bearings should be carefully monitored, particularly young
      women implanted with large diameter heads. Since large diameter ceramic-on
      ceramic bearings seem to do well we support their continued use. FUNDING:
      National Joint Registry of England and Wales.

PMID- 22417411
TI  - Nonvolatile taste compounds in cooked Chinese Nanjing duck meat following
      postproduction heat treatment.
AB  - Taste-active compounds, including free amino acids, succinic acid and 5'
      nucleotides, and chemical components including moisture, pH, protein, crude fat,
      and sodium chloride were evaluated in cooked and packaged Chinese Nanjing ducks
      following heat treatments including control, 99  degrees C for 40 min, 108 
      degrees C for 20 min, 92  degrees C microwave followed by water heating, 95 
      degrees C for 30 min, 121  degrees C for 25 min. Heat treatment decreased (P <
      0.05) the content of Alamine and moisture and reduced the pH value in muscle, but
      increased (P < 0.05) the protein and 5'-nucleotides content. The 99  degrees C
      group had a significantly lower crude fat content compared with other groups (P <
      0.05). The succinic acid content in the control group was significantly higher
      than in the 121  degrees C group (P < 0.05). Groups treated at higher
      temperatures (108  degrees C, 121  degrees C, and microwave) had similar
      equivalent umami concentrations and 5'-nucleotides, free amino acids content, as
      well as the derived bitter and sweet taste components compared with the groups
      treated at lower temperatures. It can be speculated that these differences
      account for the enhanced flavor of the meat in the 99  degrees C, 108  degrees C,
      121  degrees C, and microwave groups compared with the untreated control.
      Therefore, heat treatment at lower temperature after packaging may prolong
      product shelf life without any detrimental effects on taste. The results of this
      study indicate that it is important to use lower temperatures in this type of
      food processing. However, it may be possible to modify the primary processing
      steps to improve the content of umami-like taste compounds such as 5'
      nucleotides. PRACTICAL APPLICATION: Heat treatment of packaged products is an
      effective method for eradication of microbes, therefore increasing the shelf
      life. However, such treatment can result in major changes in the sensory
      perception of meat products, particularly the formation of off-flavors. This
      study investigated changes in taste-active compounds in duck meat following a
      number of types of heat treatment.

PMID- 22417412
TI  - Optimization of ultrasonic-assisted enzymatic hydrolysis for the extraction of
      luteolin and apigenin from celery.
AB  - The extraction of flavonoids is of increasing interest because of their various
      pharmacological effects. This study is the first attempt for the ultrasonic
      assisted enzymatic hydrolysis (USAEH) applied in the extraction of 2 bioactive
      flavonoid compounds in celery--luteolin and apigenin. The quantitative yields of
      luteolin and apigenin were determined by high-performance liquid chromatography
      (HPLC). To achieve high yields of extracted compounds, the procedure was
      optimized with regard to the relative parameters involved. The optimal conditions
      for enzymatic hydrolysis using pectinase treatment were a reaction time of 30 min
      and a concentration of 0.4 mg/mL at pH 3 for luteolin and pH 5.5 for apigenin.
      The optimal ultrasonic parameters were an exposure period of 30 min at a
      temperature of 25  degrees C using a power source of 80 W. Under these optimal
      conditions, the yields of luteolin and apigenin were increased to 42.5 and 25.3
      mg/g, respectively, which represented a 26.1-fold and a 32.2-fold increase in the
      yields of these 2 compounds, respectively, compared with the control model of
      aqueous extraction without enzyme or ultrasonic treatment.

PMID- 22417413
TI  - Structural stability of myosin rod from silver carp as affected by season.
AB  - Chymotrypsin digestion and Circular dichroism (CD) spectroscopy were used to
      study the structural stability of myosin rods prepared from silver carp in summer
      and winter. Differences in the thermal stability were clearly demonstrated by the
      chymotryptic digestion patterns and CD data obtained at pH 7.5 in 0.5 M KCl for
      myosin rods in both seasons, indicating the structural properties differed
      seasonally. In winter, the myosin rods were more susceptible to be cleaved into
      short (40 kDa) subfragments when digested at high temperature (30  degrees C).
      The major peaks in unfolding profiles showed that transition temperatures for the
      rods were 35  degrees C in winter, and 36 and 41  degrees C in summer. Rod
      subfragments (S-2 and LMM) were isolated and further analyzed by CD. In both
      winter and summer, the LMM fragments showed an unfolding transition at around
      35.5  degrees C, but the S-2 fragments showed large seasonal difference; in
      winter, they showed a major unfolding peak around 35  degrees C and a minor peak
      at 40.5  degrees C, while in summer, they unfolded mostly at 44.5  degrees C,
      which was 8  degrees C higher than that for the LMM fragments. Short (40 kDa) S-2
      subfragments isolated from winter rods gave a single unfolding transition at 41 
      degrees C. These results suggest that differences in the thermal stability of
      myosin rods between winter and summer were due to differences in the stability of
      S-2 region. PRACTICAL APPLICATION: The aim of this study was to detect the
      differences in the structure thermal stability of myosin rods between summer and
      winter, which is a very important portion for gel formation. The information will
      be very useful for producing surimi from freshwater fish species in different
      seasons.

PMID- 22417414
TI  - Prooxidant effects of the combination of green tea extract and sodium nitrite for
      accelerating lipolysis and lipid oxidation in pepperoni during storage.
AB  - The individual and interactive effects of green tea (GT) extract and sodium
      nitrite (NT) on lipolysis and lipid oxidation were investigated in pepperoni
      during processing and storage (4  degrees C). Pepperoni was treated with GT at
      concentrations of 0.02%, 0.05%, 0.1%, 0.2%, 0.5%; and NT from 0.003% to 0.015% in
      increments of 0.003%; and a combination of 0.05% GT and 0.009% NT (GT/NT). The
      pH, color, residual nitrite, fatty acid (FA), and 2-thiobarbituric acid reactive
      substances (TBARS) values were measured. The results showed inhibitory effects on
      TBARS value were concentration dependent. The largest effect was at 0.05% for GT
      and 0.009% for NT. Adding 0.05% GT significantly decreased (P < 0.05) the TBARS
      values but did not affect color values during storage. NT (0.009%) was more
      effective than GT (0.05%) for maintaining lower TBARS values (P < 0.05). Total
      fatty acids were not affected by 0.05% GT and 0.009% NT treatments. However,
      adding GT/NT showed a significant prooxidant effect (P < 0.05) in pepperoni,
      which accelerated lipolysis and lipid oxidation significantly (P < 0.05) during
      storage, with depletion of nitrite. This suggests that adding GT and an
      appropriate amount of NT into pepperoni could promote lipolysis and lipid
      oxidation during storage, as compared to NT alone. PRACTICAL APPLICATION: When
      using GT extract as an antioxidant in industrial production of pepperoni, the
      interaction effect with NT should be considered, as it may lead to a prooxidant
      effect during refrigerated storage.

PMID- 22417415
TI  - Comparison and characterization of the antioxidant potential of 3 wild grapes-
      Vitis thunbergii, V. flexuosa, and V. kelungeusis.
AB  - This study considers a laboratory examination of the antioxidant performance of
      methanolic extracts from the leaves and stems of 3 common wild grapes (Vitis
      thunbergii, V. flexuosa, and V. kelungeusis) by various in vitro methods. It also
      seeks to identify the specific antioxidant constituent. Results revealed that, of
      these specimens, stem extracts of V. thunbergii exhibited good 1,1-diphenyl-2
      picrylhydrazyl radical-scavenging and superoxide radical-scavenging performance
      and ferrous ion-chelating ability, as well as the highest total phenolic content
      (179.5 mg of GAE/g). The principal antioxidant, (+)-lyoniresinol-2a-O-beta-D
      glucopyranoside, was isolated from the stem extracts of V. thunbergii and
      identified. Removal of this compound from the extracts caused an approximate 2-
      to 5-fold decrease in antioxidant performance. This showed that (+)-lyoniresinol
      2a-O-beta-D-glucopyranoside is the primary antioxidant in wild grapes. Results
      also indicated that the antioxidant performance of (+)-lyoniresinol-2a-O-beta-D
      glucopyranoside was stronger than its lignan aglycone, (+)-lyoniresinol.
      PRACTICAL APPLICATION: Of the 3 common wild grapes-Vitis thunbergii, V. flexuosa,
      and V. kelungeusis, the extracts or phytochemicals, derived from the V.
      thunbergii stems have excellent antioxidant properties, so they have great
      potential as a basis for natural health products that seek to prevent diseases
      caused by the overproduction of radicals.

PMID- 22417416
TI  - Antioxidant capacities of phenolic compounds and tocopherols from Tunisian
      pomegranate (Punica granatum) fruits.
AB  - This article aims to determine the phenolic, tocopherol contents, and antioxidant
      capacities from fruits (juices, peels, and seed oils) of 6 Tunisian pomegranate
      ecotypes. Total anthocyanins were determined by a differential pH method.
      Hydrolyzable tannins were determined with potassium iodate. The tocopherol (alpha
      tocopherol, gamma-tocopherol, and delta-tocopherol) contents were, respectively,
      165.77, 107.38, and 27.29 mg/100 g from dry seed. Four phenolic compounds were
      identified and quantified in pomegranate peel and pulp using the high-performance
      liquid chromatography/ultraviolet method: 2 hydroxybenzoic acids (gallic and
      ellagic acids) and 2 hydroxycinnamic acids (caffeic and p-coumaric acids). Juice,
      peel, and seed oil antioxidants were confirmed by ferric reducing antioxidant
      power (FRAP) and oxygen radical absorbance capacity (ORAC) methods. The highest
      values were recorded in peels with 25.63 mmol trolox equivalent/100 g and 22.08
      mmol TE/100 g for FRAP and ORAC assay, respectively. Results showed that the
      antioxidant potency of pomegranate extracts was correlated with their phenolic
      compound content. In particular, the highest correlation was reported in peels.
      High correlations were also found between peel hydroxybenzoic acids and FRAP ORAC
      antioxidant capacities. Identified tocopherols seem to contribute in major part
      to the antioxidant activity of seed oil. The results implied that bioactive
      compounds from the peel might be potential resources for the development of
      antioxidant function dietary food.

PMID- 22417417
TI  - Effect of pilot-scale aseptic processing on tomato soup quality parameters.
AB  - Tomatoes are often processed into shelf-stable products. However, the different
      processing steps might have an impact on the product quality. In this study, a
      model tomato soup was prepared and the impact of pilot-scale aseptic processing,
      including heat treatment and high-pressure homogenization, on some selected
      quality parameters was evaluated. The vitamin C content, the lycopene isomer
      content, and the lycopene bioaccessibility were considered as health-promoting
      attributes. As a structural characteristic, the viscosity of the tomato soup was
      investigated. A tomato soup without oil as well as a tomato soup containing 5%
      olive oil were evaluated. Thermal processing had a negative effect on the vitamin
      C content, while lycopene degradation was limited. For both compounds, high
      pressure homogenization caused additional losses. High-pressure homogenization
      also resulted in a higher viscosity that was accompanied by a decrease in
      lycopene bioaccessibility. The presence of lipids clearly enhanced the lycopene
      isomerization susceptibility and improved the bioaccessibility. PRACTICAL
      APPLICATION: The results obtained in this study are of relevance for product
      formulation and process design of tomato-based food products.

PMID- 22417418
TI  - Composition of flavonoids and phenolic acids in lychee (Litchi Chinensis Sonn.)
      Flower extracts and their antioxidant capacities estimated with human LDL,
      erythrocyte, and blood models.
AB  - Lychee (Litchi chinensis Sonn.) flower is a major nectar source in Taiwan.
      Antioxidant activities of acetone, ethanol, and hot-water extracts of the flower
      were estimated through three biochemical models: inhibition of Cu(2+) -induced
      oxidation of human low-density lipoprotein, scavenging ability of oxygen radicals
      in human blood, and inhibition of human erythrocyte hemolysis induced by peroxyl
      radicals. Composition and content of flavonoids and phenolic acids in these
      extracts were also determined by high-performance liquid chromatography. Results
      showed that antioxidant effects of all test models as well as contents of
      flavonoids and phenolic acids for the lychee flower extracts were in the order:
      acetone extract > ethanol extract > hot-water extract. Gentistic acid and
      epicatechin were the major phenolic acid and flavonoid in the extracts,
      respectively.

PMID- 22417419
TI  - Quality, bioactive compounds, and antioxidant activity of new flat-type peach and
      nectarine cultivars: a comparative study.
AB  - In this work, some organoleptic and nutritive parameters related to fruit quality
      (color, firmness, total soluble solids, and total acidity), the content of
      bioactive compounds (total phenolics and total carotenoids) as well as the total
      antioxidant activity (TAA) due to hydrophilic (H-TAA) and lipophilic (L-TAA)
      compounds have been determined in both skin and flesh of 10 flat peach and
      nectarine genotypes (7 peaches and 3 nectarines). Results showed that genotype
      plays an important role in determining the organoleptic and nutritive quality, as
      well as the concentration of bioactive compounds and the related TAA, since these
      parameters differed largely among cultivars. Overall data suggest that for
      commercial purposes and consumer's acceptability (based on color, firmness,
      acidity, and bioactive compounds), the flat nectarine "ASF-06-83" and the flat
      peaches "Sweet Cap" and "ASF-06-91" could be considered as the best cultivars.
      Additionally, it is suggested that the content of bioactive compounds should be
      included as an important factor in future breeding program to obtain new
      genotypes with enhanced bioactive compounds. PRACTICAL APPLICATION: Genotype of
      flat peaches and nectarines plays an important role in determining the
      organoleptic and nutritive quality, as well as the content of bioactive
      compounds. Given the differences on bioactive compounds concentration and
      antioxidant activity among peaches and nectarines flat cultivars, these
      parameters should be included as an important factor in future breeding program
      to obtain new genotypes with enhanced bioactive compounds.

PMID- 22417420
TI  - Chemical composition and nutritive value of lantana and sweet pepper seeds and
      nabak seed kernels.
AB  - Chemical analysis was carried out on lantana (Lantana camara) and sweet pepper
      (Capsicum annuum L.) seeds and nabak (Zizyphus spina-christi) seed kernels. The
      proximate analysis (on dry weight basis) of sweet pepper seeds, lantana seeds,
      and nabak seed kernels showed the following composition: moisture 70.95%, 17.27%,
      and 4.22%; ash 4.88%, 1.81%, and 3.51%; fat 19.57%, 11.0%, and 30.19%; crude
      protein 19.28%, 6.3%, and 38.2%; and carbohydrate 56.3%, 80.9%, and 28.1%,
      respectively. For minerals, potassium was the most abundant element, followed by
      phosphorus and sodium. Also, zinc, iron, copper, and manganese were detected.
      Analysis of amino acids revealed that the first limiting amino acid was valine,
      for both lantana and sweet pepper seeds, but it was threonine for nabak seed
      kernels. Antinutritional compounds, including, phytic acid, trypsin inhibitor,
      and tannins, were detected in all seeds. Results of fatty acid compositions
      showed that the major fatty acid was oleic acid in both lantana (48.73%) and
      nabak oils (53.25%), but it was linoleic acid in sweet pepper oil (71.55%).
      Moreover, the degree of unsaturation of these oils was close to that of common
      vegetable oils. In all oils, there was absorbance in the ultraviolet (UV)-B and
      UV-C ranges with potential for use as broad spectrum UV protectants. It can be
      inferred that the seeds investigated are good sources of crude fat, crude
      protein, ash, carbohydrate, and some minerals. Furthermore, the oil extracts
      could be useful as edible oils and for industrial applications. PRACTICAL
      APPLICATION: The nutritional composition of the investigated seeds suggested that
      they could be used to meet part of the nutritional requirements of animal feeds.
      Also, they could be regarded as good sources of food ingredients and as new
      sources of edible oils.

PMID- 22417421
TI  - Polymeric proanthocyanidins in skins and seeds of 37 Vitis vinifera L. cultivars:
      a methodological comparative study.
AB  - The polymeric proanthocyanidins (PAs) composition of skins and seeds from
      different Vitis vinifera L. cv. was evaluated, sampling 37 cultivar, preserved in
      the grapevine collection of Grinzane Cavour (Piedmont, Italy). PAs were
      quantified using both spectrophotometric (n-butanol and vanillin assay) and
      chromatographic (high-performance liquid chromatography [HPLC]) methods, and the
      evaluation of their antioxidant activity was performed using the 2,2-diphenyl-1
      picrylhydrazyl (DPPH) scavenging assay. Results of PAs quantification with the
      different methods were significantly correlated. A strong correlation pointed out
      between anthocyans and PAs content (particularly regarding HPLC method; r =
      0.9359, P = 0), and the antioxidant activity was not dependent on the polymeric
      PAs content, but negatively correlated with the degree of polymerization (r =
      0.6102, P = 1 * 10-4). The hierarchical clustering on principal components
      analysis allowed grouping the samples in 3 different clusters, observing a direct
      association between the cluster classification and the anthocyans/PAs content.

PMID- 22417422
TI  - Fatty acid synthase inhibitors separated from oiltea camellia by high-speed
      counter-current chromatography.
AB  - The inhibitory effects of oiltea camellia extracts (OCEs) and its active
      components on fatty acid synthase (FAS) were investigated. OCE potently inhibited
      the activity of FAS with an half-maximal inhibitory concentration (IC50) value of
      2.30 MUg/mL. The inhibition kinetic results showed that OCE and acetyl-CoA
      competitively inhibited FAS but these compounds exhibited mixed inhibition
      against malonyl-CoA and NADPH. Further study uncovered that the active components
      of OCE, ellagic acid (EA) and 3-O-methylellagic acid 4'-O-beta-D-glucopyranoside
      (MEAG), which were isolated and purified by high-speed counter-current
      chromatography (HSCCC) using a 2-phase solvent system of chloroform-ethanol-water
      acetic acid (4:3:2:0.01, v/v/v/v), inhibited FAS with IC50 of 2.50 and 37.73
      MUg/mL, respectively. Their inhibition kinetics were different from that of OCE.
      Both of them exhibited uncompetitive inhibition for nicotinamide adenine
      dinucleotide phosphate (NADPH) and decreased the FAS activity through
      inactivation of acetyl/malonyl transferase on FAS. These results suggest that OCE
      could be a valuable resource for bioactive substances. PRACTICAL APPLICATION:
      With the gradual increase in tea oil production, it was in urgent need of dealing
      with Camellia fruit hull, which was always discarded because of low economic
      benefits. Camellia fruit hull has been shown to have significant antioxidant
      effects including 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging
      ability and ferric-reducing antioxidant power. This study found that the
      ethanolic extract of Camellia fruit hull at low concentration efficiently
      inhibited FAS activity, which is a potential therapy target of both obesity and
      cancer. These results suggest that OCE could be a valuable resource for bioactive
      substances.

PMID- 22417423
TI  - Improving chocolate flavor in poor-quality cocoa almonds by enzymatic treatment.
AB  - This paper proposes a method to enzymatically treat poor-quality cocoa almonds
      (known as "slate") to ensure the formation of chocolate flavor precursors. The
      production of flavor precursors improves the quality of these almonds, which are
      usually responsible for the low quality of the liquor produced. Proteases and
      carboxypeptidases from different sources were tested under various conditions.
      The different treatments were evaluated by chemical analysis (hydrolysis
      efficiency) and sensory analysis of the treated material compared to good-quality
      cocoa almonds. The results show that it is possible, through the use of microbial
      enzymes, to generate the mixture of compounds that will release, after roasting,
      the characteristic chocolate flavor in poor-quality almonds. However, it is
      necessary to optimize the conditions of enzymatic treatment to obtain better
      results and thus establish a process that can be used for industrial purposes for
      manufacturing cocoa and chocolate. PRACTICAL APPLICATION: The basidiomycete
      Moniliophtora perniciosa is the causative agent of witches' broom disease (WBD)
      of the cocoa tree, whose seeds are the source of chocolate. It is the most
      important phytopathological problem of cocoa-producing areas of the American
      continent, and has decimated the Brazilian cocoa industry. In Bahia (Brazil), M.
      perniciosa was identified in 1989 and, as a consequence of its spreading, the
      annual production of cocoa almonds dropped from 450,000 to 90,000 tons within 12
      y, reducing export values from an all-time high of about US$ 1 billion to 110
      million. The high incidence of WBD incapacitates Brazil to produce enough cocoa
      almonds even for the internal market, leading the country to import low-quality
      cocoa almonds mainly from African countries. Our work proposes an enzymatic
      treatment to increase the quality of that cocoa almonds and, consequently, to
      improve the quality of the chocolate produced and consumed in the country.

PMID- 22417424
TI  - Mild protein oxidation enhanced hydration and myofibril swelling capacity of
      fresh ground pork muscle packaged in high oxygen atmosphere.
AB  - This study investigated the influence of an oxygen-enriched modified atmosphere
      packaging (HiOx: 80% O2/20% CO2) in comparison with air-permeable
      polyvinylchloride (PVC) wrapping and partial vacuum (VP: 60%) packaging on the
      ability of myofibrils to imbibe water during retail display of fresh ground pork
      at 2 to 4  degrees C. Both HiOx and PVC muscles after 4 d showed maximum
      myofibril swelling and A-band dissolution when isolated myofibrils were subjected
      to a graded series of salt solutions (0.2->0.4 M NaCl with 10-mM sodium
      pyrophosphate, pH 6.2), while VP samples exhibited no remarkable change. Protein
      carbonyl content increased substantially from day 0 to 4 in all muscle samples.
      For HiOx, muscle hydration capacity increased linearly (P < 0.05) during storage
      up to 14 d, corresponding to protein carbonyl production. No significant changes
      in hydration properties were noted in VP muscle samples, which also maintained
      lower levels of protein oxidation, during storage up to 21 d. These results
      indicated that packaging in modified atmosphere with high levels of oxygen could
      result in increased protein oxidation but enhanced hydration capacity of fresh
      meat. PRACTICAL APPLICATION: Packaging of fresh meat, including ground pork,
      under an oxygen-enriched atmosphere condition is widely used in the industry to
      preserve red color of meat. Results from the present study indicate that high
      oxygen packaging has a discordant effect on fresh ground pork: it enhances
      hydration but decreases water-binding, and this seems to be caused by increased
      swelling of muscle fibers due to mild protein oxidation. Hence, it is advisable
      to employ a water-binding agent in this type of packaging system so as to retain
      the moisture in stored fresh pork products while maintaining the color stability.

PMID- 22417425
TI  - Volatile profile of cashews (Anacardium occidentale L.) from different
      geographical origins during roasting.
AB  - Volatile compounds were quantified in the headspace of Indian, Vietnamese, and
      Brazilian cashews, both raw and during roasting by selected ion flow tube-mass
      spectrometry. The optimum roasting times based on color measurements were also
      determined. Raw cashews were oil roasted for 3 to 9 min at 143  degrees C and
      color and volatiles measured. An excellent correlation, following a pseudo 1st
      order reaction, was found between L* value and roasting time; darkness increases
      as roasting time increases. The optimum roasting time was 6, 8, and 9 min for
      Vietnamese, Indian, and Brazilian cashews, respectively. Raw cashews had lower
      concentrations of volatiles than roasted cashews. Most volatiles significantly
      increased in concentration during roasting of Brazilian, Indian, and Vietnamese
      cashews. Only a few volatiles significantly decreased during roasting. Ethanol
      and 1-heptene significantly decreased during roasting in Brazilian cashews and
      toluene decreased in Vietnamese cashews. Brazilian cashews had significantly
      higher levels of most volatiles than Indian and Vietnamese cashews. Most volatile
      levels in Indian and Vietnamese cashews were not significantly different. Of the
      volatiles, Strecker aldehydes, including methylbutanal, 2-methylpropanal, and
      acetaldehyde, were at the highest concentration in roasted cashews. The Maillard
      reaction contributed to the formation of most of the volatiles in cashews from
      the 3 countries. There was also degradation of sugars to form furan-type
      compounds and oxidation of lipids to form alkanals such as hexanal. PRACTICAL
      APPLICATION: The volatile profile during roasting of cashews can be used to
      determine the best roasting time for each type of cashew. The rate of color
      development and the production of volatiles differ for the cashews from the 3
      geographical locations.

PMID- 22417426
TI  - Seasonal changes of alpha-tocopherol in green marine algae (Caulerpa genus).
AB  - Marine algae are a promising source of beneficial compounds for human use. Among
      these, pro-vitamin A carotenoids and vitamins B, C, and E stand out. The
      objective of this study was to investigate seasonal variation of alpha-tocopherol
      levels in 5 species of green marine algae of the Caulerpa genus. This research
      was carried out with both fresh and dry specimens; and, in addition, differences
      arising as a result of the drying process were examined. Analyses were carried
      out by high-performance liquid chromatography (HPLC) using an isocratic system
      and a reversed-phase C-18 column. The distribution of alpha-tocopherol throughout
      the year in Caulerpa genus was variable. All samples of both fresh and dried
      algae contained alpha-tocopherol, except for the dried C. racemosa from March
      2006. The drying process was responsible for losses of alpha-tocopherol ranging
      from 21% to 93%.

PMID- 22417427
TI  - Optimization of fermentation conditions for production of the jabuticaba
      (Myrciaria cauliflora) spirit using the response surface methodology.
AB  - The jabuticaba tree (Brazilian grape tree) is a tree native to Brazil that
      belongs to the Myrtaceae family. The jabuticaba fruit is used in some regions of
      Brazil to produce juices, jams, wine, and ice cream. In this work, the
      fermentation conditions (temperature and  degrees Brix) for producing jabuticaba
      distillate were optimized using the response surface methodology (RSM). The
      optimal conditions for fermentation were found to be 20  degrees C and 22 
      degrees Brix. In repeated experiments to validate the model, experimental data
      exhibited good agreement with the predicted data. The distillate jabuticaba
      beverage showed a peculiar chemical composition with 20 volatile compounds that
      were identified and quantified. Isoamyl alcohols (2-methyl-1-butanol + 3-methyl-1
      butanol) were the most abundant volatile compounds identified in jabuticaba
      spirit. Sensory analysis by tasters showed overall approval of jabuticaba
      distillate. In principal component analysis, when the beverage was evaluated by
      panelists under 24 y old tended to give favorable ratings of aroma and taste, as
      well as high overall scores. The group of panelists between the ages of 25 and 53
      y old generally gave high marks for appearance in the principal component
      analysis. PRACTICAL APPLICATION: This study describes the study of fermentation
      conditions of jabuticaba pulp for production of jabuticaba spirit. Based on the
      results of this work, the proposed method can be an alternative for the use of
      the jabuticaba fruit, and may provide a new industrial outlet for this fruit.

PMID- 22417428
TI  - Damage in agitated vessels of large visco-elastic particles dispersed in a highly
      viscous fluid.
AB  - Many food recipes entail several homogenization steps for solid particles in hot
      or cold viscous liquids, such as pureed fruit and sugar, jam or sauce with
      mushroom pieces. Unfortunately, these unavoidable processes induce damage to the
      solid particles. To date, little is known of the extent and nature of the damage
      caused. Consequently, few clear guidelines are available for monitoring solid
      particle integrity when mixing solid/liquid suspensions in an agitated tank. In
      this study, an attempt is made to quantify the impact of various physical
      parameters including the influence of the rotational speed of the impeller and
      the processing time on particle attrition, when a suspension of large visco
      elastic particles in a highly viscous fluid is mixed under isothermal condition.
      Pectin gel particles were immerged in a viscous liquid and homogenized for
      various times and rotational speeds, while the evolution of the particle's
      morphological parameters was monitored. Then, a set of dimensionless numbers
      governing the attrition mechanism is established and some empirical process
      relationships are proposed to correlate these numbers to the morphological
      characteristics and mass balance ratios. From the conditions observed, it is
      clear that 2 dimensionless ratios could be responsible for a change in the
      damaging mechanisms. These 2 ratios are the Froude and impeller rotation numbers.
      Finally, in the conditions tested, mass balance ratios appear to be mainly
      sensitive to the impeller rotational number, while the shape ratios are both
      impacted by the Froude and impeller rotational numbers. PRACTICAL APPLICATION:
      Damage to solid particles suspended in a stirred vessel reduce the final product
      quality in industrial cooking processes. Examples of this are fruit in jam or
      sauces with mushroom pieces. The attrition phenomenon was measured and the
      influences of the impeller rotational speed and processing time were evaluated
      quantitatively in function of dimensionless numbers. This study contributes key
      elements for the monitoring of damage to solids with a view to retaining solid
      integrity.

PMID- 22417429
TI  - Effect of soy addition on microwavable pocket-type flat doughs.
AB  - Microwavable frozen baked goods are widely used by the food industry. However,
      the altered heat and mass transfer patterns associated with microwave radiation
      result in tough and rubbery baked products due to reduced plasticization of the
      polymers. Ingredients with high water-holding capacity and high content of polar
      lipids have been shown to enhance gluten plasticization and to improve water
      retention. Therefore, this study explored the physicochemical changes imparted by
      microwave baking of pocket-type flat doughs with and without soy added at 10%,
      20%, and 26% and compared these to their conventionally baked counterparts.
      Microwave baking resulted in a soft, rubbery, and tough wheat product with
      increased "freezable" water. Soy was added to the formulation as a means to
      improve polymer plasticization. Conventional baking of soy doughs resulted in
      rubbery and tough products due to changes in water state and mobility (freezable
      water approximately 15 compared with 7.09 of the control). However, soy reduced
      the cohesiveness of the microwave baked products reaching the lowest value at 20%
      soy addition (cohesiveness 0.33 +/- 1, comparable to that of the conventionally
      baked control). These data suggest that reduction of water mobility induced by
      soy proteins and polar lipids (confirmed by thermogravimetric analysis [TGA] and
      1H nuclear magnetic resonance [1H NMR]) possibly plasticized the starch-gluten
      network of microwave baked soy doughs. Thus, soy was shown to improve the texture
      of microwave baked pocket-type flat doughs although further formula optimization
      is warranted. PRACTICAL APPLICATION: Microwavable pocket-type flat doughs are
      used frequently by the food industry to enrobe meat, vegetable, and sweet items
      for convenient meal delivery. Microwave heating of such doughs induces the
      development of crustless products compared to conventionally baked products,
      resulting in a tough and rubbery texture. Partial substitution of wheat flour
      with soy, in the form of soy flour and soy milk powder, prevented the deleterious
      textural changes associated with microwave heating. These results suggest that
      soy is a functional ingredient for the textural improvement of microwavable
      pocket-type flat doughs.

PMID- 22417430
TI  - High-pressure effects on the microstructure, texture, and color of white-brined
      cheese.
AB  - White-brined cheeses were subjected to high-pressure processing (HPP) at 50, 100,
      200, and 400 MPa at 22  degrees C for 5 and 15 min and ripened in brine for 60 d.
      The effects of pressure treatment on the chemical, textural, microstructural, and
      color were determined. HPP did not affect moisture, protein, and fat contents of
      cheeses. Similar microstructures were obtained for unpressurized cheese and
      pressurized cheeses at 50 and 100 MPa, whereas a denser and continuous structure
      was obtained for pressurized cheeses at 200 and 400 MPa. These microstructural
      changes exhibited a good correlation with textural changes. The 200 and 400 MPa
      treatments resulted in significantly softer, less springy, less gummy, and less
      chewy cheese. Finally, marked differences were obtained in a* and b* values at
      higher pressure levels for longer pressure-holding time and were also supported
      by DeltaE* values. The cheese became more greenish and yellowish with the
      increase in pressure level. PRACTICAL APPLICATION: The quality of cheese is the
      very important to the consumers. This study documented the pressure-induced
      changes in selected quality attributes of semisoft and brine-salted cheese. The
      results can help the food processors to have knowledge of the process parameters
      resulting in quality changes and to identify optimal process parameters for
      preserving pressure-treated cheeses.

PMID- 22417431
TI  - Online shear viscosity measurement of starchy melts enriched in wheat bran.
AB  - Addition of wheat bran to flours modifies their expansion properties after
      cooking extrusion. This can be attributed to changes in the melt shear viscosity
      at the die. The effect of wheat bran concentration added to achieve 2 levels of
      dietary fibers of 12. 6% and 24.4%, and process conditions on the shear viscosity
      of wheat flour was therefore assessed using an online twin-slit rheometer. The
      shear viscosity measured at 30 s-1 ranged from 9.5 * 103 to 53.4 * 103 Pa s.
      Regardless of the process conditions and bran concentration, the extruded melts
      showed a pseudoplastic behavior with a power law index n ranging from 0.05 to
      0.27. Increasing the barrel temperature of the extruder from 120 to 180  degrees
      C, the water content from 18% to 22% or the screw speed from 400 to 800 rpm
      significantly decreased the melt shear viscosity at the extruder exit. The
      addition of bran significantly increased the melt shear viscosity only at the
      highest bran concentration. The effect was process condition dependant.
      Mathematical interpretations, based upon observations, of the experimental data
      were carried out. They can be used to predict the effect of the process
      conditions on the melt shear viscosity at the die of extruded wheat flour with
      increasing bran concentration. The viscosity data will be applied in future works
      to study the expansion properties of extruded wheat flour supplemented with bran.
      PRACTICAL APPLICATION: Incorporation of wheat bran, a readily available and low
      cost by-product, in extruded puffed foods is constrained due to its negative
      effect on the product texture. Understanding the effect of wheat bran on
      rheological properties of extruded melts, driving the final product properties,
      is essential to provide solutions to the food industry and enhance its use.

PMID- 22417432
TI  - In vitro batch fecal fermentation comparison of gas and short-chain fatty acid
      production using "slowly fermentable" dietary fibers.
AB  - Sustained colonic fermentation supplies beneficial fermentative by-products to
      the distal colon, which is particularly prone to intestinal ailments.
      Blunted/delayed initial fermentation may also lead to less bloating. Previously,
      we reported that starch-entrapped alginate-based microspheres act as a slowly
      fermenting dietary fiber. This material was used in the present study to provide
      a benchmark to compare to other "slowly fermentable" fibers. Dietary fibers with
      previous reports of slow fermentation, namely, long-chain inulin, psyllium,
      alkali-soluble corn bran arabinoxylan, and long-chain beta-glucan, as well as
      starch-entrapped microspheres were subjected to in vitro upper gastrointestinal
      digestion and human fecal fermentation and measured over 48 h for pH, gas, and
      short-chain fatty acids (SCFA). The resistant fraction of cooked and cooled
      potato starch was used as another form of fermentable starch and
      fructooligosaccharides (FOS) served as a fast fermenting control. Corn bran
      arabinoxylan and long-chain beta-glucan initially appeared slower fermenting with
      comparatively low gas and SCFA production, but later fermented rapidly with
      little remaining in the final half of the fermentation period. Long-chain inulin
      and psyllium had slow and moderate, but incomplete, fermentation. The resistant
      fraction of cooked and cooled potato starch fermented rapidly and appeared
      similar to FOS. In conclusion, compared to the benchmark slowly fermentable
      starch-entrapped microspheres, a number of the purported slowly fermentable
      fibers fermented fairly rapidly overall and, of this group, only the starch
      entrapped microspheres appreciably fermented in the second half of the
      fermentation period. PRACTICAL APPLICATION: Consumption of dietary fibers,
      particularly commercial prebiotics, leads to uncomfortable feelings of bloating
      and flatulence due to their rapid degradation in our large intestine. This
      article employs claimed potential slowly fermenting fibers and compares their
      fermentation rates with a benchmark slow fermenting fiber that we fabricated in
      an in vitro simulation of the human digestive system. Results show a variety of
      fermentation profiles only some of which have slow and extended rate of
      fermentation.

PMID- 22417433
TI  - Bioactive dietary polyphenols inhibit heme iron absorption in a dose-dependent
      manner in human intestinal Caco-2 cells.
AB  - Although heme iron is an important form of dietary iron, its intestinal
      absorption mechanism remains elusive. Our previous study revealed that (-)
      epigallocatechin-3-gallate (EGCG) and grape seed extract (GSE) markedly inhibited
      intestinal heme iron absorption by reducing the basolateral iron export in Caco-2
      cells. The aim of this study was to examine whether small amounts of EGCG, GSE,
      and green tea extract (GT) could inhibit heme iron absorption, and to test
      whether the inhibitory action of polyphenols could be offset by ascorbic acid. A
      heme-55Fe absorption study was conducted by adding various concentrations of
      EGCG, GSE, and GT to Caco-2 cells in the absence and presence of ascorbic acid.
      Polyphenolic compounds significantly inhibited heme-55Fe absorption in a dose
      dependent manner. The addition of ascorbic acid did not modulate the inhibitory
      effect of dietary polyphenols on heme iron absorption when the cells were treated
      with polyphenols at a concentration of 46 mg/L. However, ascorbic acid was able
      to offset or reverse the inhibitory effects of polyphenolic compounds when lower
      concentrations of polyphenols were added (<= 4.6 mg/L). Ascorbic acid modulated
      the heme iron absorption without changing the apical heme uptake, the expression
      of the proteins involved in heme metabolism and basolateral iron transport, and
      heme oxygenase activity, indicating that ascorbic acid may enhance heme iron
      absorption by modulating the intracellular distribution of 55Fe. These results
      imply that the regular consumption of dietary ascorbic acid can easily counteract
      the inhibitory effects of low concentrations of dietary polyphenols on heme iron
      absorption but cannot counteract the inhibitory actions of high concentrations of
      polyphenols. PRACTICAL APPLICATION: Bioactive dietary polyphenols inhibit heme
      iron absorption in a dose-dependent manner. The small amounts of polyphenolic
      compounds present in foods are capable of reducing heme iron transport across the
      intestinal enterocyte. However, the inhibitory effects of dietary polyphenolic
      compounds on heme iron absorption can be offset by ascorbic acid and can possibly
      be avoided by decreasing the consumption of polyphenols while simultaneously
      taking ascorbic acid.

PMID- 22417435
TI  - Antagonistic action of Bacillus subtilis strain fmbj on the postharvest pathogen
      Rhizopus stolonifer.
AB  - The antagonistic activities of Bacillus subtilis fmbj against the Rhizopus
      stolonifer pathogen causing peach soft rot disease were studied in this paper.
      Bacillus subtilis fmbj exhibited a high antifungal effect on the mycelium growth,
      sportulation, and germ tube elongation of R. stolonifer with the inhibition rate
      of 86.5% and 97.42%, respectively, spore germination rate of 20% under antagonist
      strain concentration of 108 CFU/mL. By using of scanning electron microscope
      (SEM) and transmission electron microscope (TEM), it was observed that B.
      subtilis fmbj strain strongly induced morphological abnormalities of R.
      stolonifer and destroyed structure of hypha and spore. When hypha cell wall of R.
      stolonifer was damaged, the organelles and cytoplasms inside cell would exude,
      which led to cell death.

PMID- 22417436
TI  - Heat-killed lactic acid bacteria enhance immunomodulatory potential by skewing
      the immune response toward Th1 polarization.
AB  - Heat-killed lactic acid bacteria not only possess immunomodulatory functions but
      also provide the advantages of longer product shelf life, easier storage, and
      more convenient transportation. To establish appropriate heat treatments for the
      industrial preparation of probiotics with immunomodulatory effects, 4 different
      heat treatments were used to kill 11 strains of lactic acid bacteria. Comparisons
      among the strains and with viable forms were carried out in terms of
      immunomodulatory activity and adhesion to Caco-2 cells. Field-emission scanning
      electron microscope (FE-SEM) was employed to observe morphological changes in
      bacteria after heating. Among the 11 viable strains, Lactobacillus gasseri AI-88
      was the strongest inducer of interferon-gamma (IFN)-gamma and interleukin (IL)
      12p70 production. However, after heat treatments its stimulatory ability was
      attenuated. Heat-killed Enterococcus faecalis YM-73 and Lactobacillus salivarius
      AP-32 strains showed enhanced stimulation of IFN-gamma and IL-12p70 secretion and
      coincidental decrease in IL-13 production. The adhesion of lactic acid bacteria
      to Caco-2 cells decreased with increases in temperature. However, heat exposure
      did not influence immunomodulatory activity. With rising temperature, roughness
      and unevenness of bacterial cell surfaces increased significantly. The results
      indicated that heat-killed E. faecalis YM-73 and L. salivarius AP-32 have
      immunomodulatory ability via increased Th1-associated cytokines and reduced Th2
      associated cytokines, switching the immune response from a Th2 toward a Th1
      response. These 2 heat-killed strains have the potential for development as
      commercial products.

PMID- 22417437
TI  - Implantation ability of the potential probiotic strain, Lactobacillus reuteri
      PL519, in "Salchichon," a traditional Iberian dry fermented sausage.
AB  - The purpose of this study was to investigate the potential of incorporating the
      probiotic L. reuteri PL519 into the manufacturing of Iberian dry fermented
      sausages, and to observe its effect on the sensory properties of these meat
      products. Specific polymerase chain reaction (PCR) was carried out to detect the
      presence of probiotic strain at high counts in the inoculated sausages. Changes
      due to probiotic inoculation on physicochemical parameters were determined and
      the impact on sensory quality evaluated. Dry fermented sausages inoculated with
      L. reuteri PL519 may be considered as functional products according to the counts
      of this strain found at the end of processing. Inoculation with L. reuteri PL519
      increased the amount of acetic acid, protein, and lipid degradation products in
      dry fermented sausages. The differences observed in the descriptive sensorial
      analysis corresponded, however, to a little impact on overall acceptability since
      no significant changes were found between the control and L. reuteri PL519 batch
      in the hedonic test. PRACTICAL APPLICATION: Processing and marketing of Iberian
      dry fermented sausages with functional characteristics.

PMID- 22417438
TI  - Determination of lactic microflora of kefir grains and kefir beverage by using
      culture-dependent and culture-independent methods.
AB  - In this study, we investigated the bacterial compositions of kefir grains and
      kefir beverages collected from different regions of Turkey by using culture
      independent and culture-dependent methods. In the culture-independent detection,
      10 different species of bacteria were detected in total by using the polymerase
      chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis of the
      16S rRNA gene V3 region. Among these species, Lactobacillus kefiranofaciens was
      the most dominant one in the kefir grains, while Lactococcus lactis was found to
      be significantly prevalent in the kefir beverages. In the culture-dependent
      detection, the primary differentiation and grouping of the isolates from kefir
      beverages and kefir grains were performed using repetitive sequence-based PCR
      (rep-PCR) fingerprinting, and the results were validated by 16S rDNA full-length
      sequencing. According to the results of culture-dependent methods, the most
      frequently isolated species were L. lactis, Leuconostoc mesenteroides, and
      Lactobacillus kefiri, respectively. Only 3 species, which are L. lactis,
      Lactobacillus acidophilus, and Streptococcus thermophilus, were detected with
      both culture-dependent and culture-independent methods. This study showed that
      the combination of both methods is necessary for a detailed and reliable
      investigation of microbial communities in kefir grains and kefir beverages.
      PRACTICAL APPLICATION: Due to their artisan- and region-dependent microflora,
      kefir products can be a source of interesting lactic acid bacteria, either new
      taxa or strains with specific functional properties, which might be used for the
      development of new starter cultures and innovative food products. Therefore, an
      increasing demand exists for new strains that show desirable effects on the
      product characteristics Artisan dairy products are a candidate source of such
      microorganisms. For this reason, in this study, the bacterial compositions of
      kefir grains and kefir beverages obtained from different regions of Turkey were
      studied using culture-dependent and culture-independent molecular methods.

PMID- 22417439
TI  - Effect of ultraviolet and far infrared radiation on microbial decontamination and
      quality of cumin seeds.
AB  - Cumin seeds might be exposed to a high level of natural bacterial contamination,
      and this could potentially create a public health risk besides leading to
      problems in exportation. Ultraviolet (UVC) and far infrared (FIR) radiation has
      low penetration power, and due to that, there might be no detrimental defects to
      the products during a possible decontamination process. Therefore, the objective
      of this study was to determine the effect of UVC and FIR treatment on microbial
      decontamination and quality of cumin seeds. For this purpose, FIR treatment at
      different exposure times and temperatures were applied followed by constant UVC
      treatment with an intensity of 10.5 mW/cm2 for 2 h. Total mesophilic aerobic
      bacteria of the cumin seeds were decreased to the target level of 104 CFU/g after
      1.57, 2.8, and 4.8 min FIR treatment at 300, 250, and 200  degrees C,
      respectively, following a 2 h UVC treatment. Under the given conditions, a
      complete elimination for total yeast and molds were obtained while there were no
      significant changes in volatile oil content and color of the cumin seeds.
      Consequently, combined UVC and FIR treatment was determined to be a promising
      method for decontamination of the cumin seeds. PRACTICAL APPLICATION: This
      research attempts to apply UVC and far infrared (FIR) radiation for
      pasteurization of cumin seeds. The data suggested that combined UVC and FIR
      radiation treatments can become a promising new method for pasteurization of
      cumin seeds without causing any detrimental defect to the quality parameters. The
      results of this industry partnered (Kadioglu Baharat, Mersin, Turkey-
      http://www.kadioglubaharat.com) study were already applied in industrial scale
      production lines.

PMID- 22417440
TI  - Rapid detection of ricin in milk using immunomagnetic separation combined with
      surface-enhanced Raman spectroscopy.
AB  - Ricin is a potential bioterrisiom agent. There is a critical need for a method
      that can rapidly and simply detect ricin and other bioterrisiom agents in complex
      food matrices such as milk. In this study, we demonstrated a rapid method that
      combined immunomagnetic separation (IMS) and surface-enhanced Raman spectroscopy
      (SERS) to detect ricin in whole milk. IMS was used to specifically capture the
      ricin out of the milk. Then, SERS was applied to analyze the IMS eluate mixed
      with silver dendrite nanosubstrates. This approach facilitated detection and
      quantification down to 4 MUg/mL ricin in milk within 20 min, based on the results
      of principal component analysis and partial least squares analysis. The
      feasibility of using a portable Raman instrument shows great promise for on-site
      detection in a processing facility. PRACTICAL APPLICATION: The method described
      in this manuscript that combined IMS and SERS could be used for rapid detection
      of ricin and other protein toxins in complex food matrices such as milk within 20
      min. The use of a portable Raman could facilitate the on-site detection in a
      processing facility.

PMID- 22417441
TI  - Sensory characteristics and consumer acceptability of red ginseng extracts
      produced with different processing methods.
AB  - The aims of this study were: to develop objective and effective sample
      preparation and presentation procedures for the sensory analysis of red ginseng
      extracts (RGE); to identify their sensory attributes in relation with the
      consumer acceptability of RGEs produced with different processing techniques. The
      samples included 7 different types of RGE, among which 2 samples were of
      commercial products and the other samples were specially prepared for the study.
      The samples differed in processing methods (traditional method, high-hydrostatic
      pressure [HHP], and fermentation) and extraction solvents (ethanol, water). For
      the descriptive analysis, 7 trained panelists developed and evaluated 30
      attributes. Principal component analysis was conducted to summarize the
      relationships between the sensory attributes and to get a representation of the
      samples according to those attributes. Consumers evaluated the appearance and
      flavor acceptability of the extracts. Hierarchical cluster analysis was conducted
      on consumer acceptability of flavor. The results showed that the clear
      differences among the RGEs in terms of sensory perceptions were explained by the
      processing methods. Consumers were segmented into 3 distinct groups in terms of
      preference: a consumer cluster that likes the RGEs produced with HHP or
      fermentation, a cluster that likes a product with strong ginseng flavor, and a
      cluster that likes a RGE with sweet taste and jujube flavor. These 3 clusters
      differed somewhat in their consumption frequency and purchase factors, also.
      PRACTICAL APPLICATION: The red ginseng extract (RGE) market is rapidly growing
      due to the consumer awareness of its superior health-promoting effects. However,
      little attention has been given to sensory properties that are a critical factor
      in determining quality and consumer preference. The results of this study will be
      helpful for researchers and manufacturers to understand the sensory
      characteristics of RGEs and to detect the driving factors of consumer
      acceptability. Also, the sample preparation and presentation procedures developed
      in this experiment will be used effectively in academia and industries to examine
      sensory characteristics of RGE products.

PMID- 22417442
TI  - Saltiness enhancement by savory aroma compounds.
AB  - The impact of elevated levels of complex savory flavorings and single aroma
      compounds on perceived saltiness was investigated. This study demonstrates that
      multisensory interaction between aroma and taste can be employed to compensate
      for the lower salt levels of healthier food products without disturbing the
      overall flavor pattern. The demonstrated saltiness enhancement by the savory
      flavorings was unraveled by experiments with "salt-congruent" single aroma
      compounds, using trained and naive panels. Several savory compounds, of different
      chemical classes and different sensory impact, could be identified as key salt
      enhancing compounds, providing a significant increase of perceived saltiness. As
      expected, an untrained, naive panel appeared more suitable to demonstrate
      multisensory saltiness enhancement due to its synthetic attention than a trained
      descriptive panel. The salt enhancement results were confirmed by consumer tests.
      The extra aroma was also found to ameliorate the off-flavor of potassium-based
      salt replacers, and combinations of extra aroma and salt replacers could replace
      significant amounts of sodium chloride while keeping the original flavor profile
      intact. PRACTICAL APPLICATION: The food industry is under high pressure to
      significantly reduce the salt levels in their products. This study shows that it
      is possible to compensate salt reduction in instant bouillons by higher levels of
      savory aroma. A combination of potassium chloride based salt replacer and extra
      aroma was found to compensate approximately 30% sodium reduction without
      significant change of the flavor profile.

PMID- 22417443
TI  - Milk processed by pulsed electric fields: evaluation of microbial quality,
      physicochemical characteristics, and selected nutrients at different storage
      conditions.
AB  - Pulsed electric fields (PEF) technology was used to pasteurize raw milk under
      selected treatments. Processing conditions were: temperature 20, 30, and 40 
      degrees C, electric field 30.76 to 53.84 kV/cm, and pulse numbers 12, 24, and 30
      for skim milk (SM), and 12, 21, and 30 for whole milk (WM) (2 MUs pulse width,
      monopolar). Physicochemical parameters (pH, electrical conductivity, density,
      color, solids nonfat [SNF]) and composition (protein and fat content) were
      measured after processing. Shelf life of SM and WM was assessed after processing
      at 46.15 kV/cm, combined with temperature (20 to 60  degrees C) and 30 pulses.
      Mesophilic and psychrophilic loads and pH were evaluated during storage at 4 and
      21  degrees C. Results showed minor variations in physicochemical properties
      after processing. There was an interesting trend in SM in SNF, which decreased as
      treatment became stronger; similar behavior was observed for fat and protein,
      showing a 0.18% and 0.17% decrease, respectively, under the strongest conditions.
      Protein and fat content decreased in WM samples treated at 40  degrees C, showing
      a decrease in protein (0.11%), and an even higher decrease in fat content. During
      storage, PEF-treated milk samples showed higher stability at 4  degrees C with
      minor variations in pH; after 33 d, pH was higher than 6. However samples at 21 
      degrees C showed faster spoilage and pH dropped to 4 after 5 d. Growth of
      mesophilic bacteria was delayed in both milks after PEF processing, showing a 6-
      and 7-log cycles for SM and WM, respectively, after day 25 (4  degrees C);
      however, psychrophilic bacteria grew faster in both cases. PRACTICAL APPLICATION:
      Pulsed electric fields (PEF) technology in the pasteurization of liquid food
      products has shown positive results. Processing times can be reduced
      considerably, which in turn reduces the loss of nutrients and offers important
      savings in energy. PEF has been used successfully to pasteurize some liquid
      foods, but it is still not used commercially in milk pasteurization, although
      several trials have shown the positive effects of PEF milk pasteurization, which
      could allow for its future use at the industrial level.

PMID- 22417444
TI  - Effect of the use of a commercial phosphate mixture on selected quality
      characteristics of 2 Spanish-style dry-ripened sausages.
AB  - The aim of this study was to evaluate the usefulness of the addition of a
      commercial phosphate mixture in 2 dry-ripened Spanish-style sausages:
      "salchichon" and "chorizo." Three batches of each of those sausages were prepared
      with low and high levels of phosphates, and selected quality variables (moisture,
      pH, a(w) , lactic and acetic acid, alpha-amino nitrogen, total free fatty acids,
      thiobarbituric acid reactive substances, microbial counts, color, and texture
      analysis) were compared against controls. Furthermore, phosphate-added and
      control sausages were ranked by consumers in order of preference. In
      "salchichon," phosphate addition resulted in a significant (P < 0.05) increase in
      drying rate, and tendencies (not significant) toward a decrease in lipid
      oxidation and an increase in hardness and chewiness. In "chorizo," the addition
      of phosphates resulted in higher hardness, elasticity and chewiness, and lower
      yellowness (P < 0.05). In the manufacture process of dry-ripened sausages,
      phosphates can be considered as additives with potential enhancement effect in
      drying and eating quality. PRACTICAL APPLICATION: The main outcome from the
      present study is to find evidence on which points of reference could be drawn for
      the technological application of phosphates in dry-ripened sausages. It has been
      observed that the drying rate and several eating quality characteristics can be
      enhanced with the use of phosphates.

PMID- 22417445
TI  - Sensory characteristics and cross-cultural consumer acceptability of Bulgogi
      (Korean traditional barbecued beef).
AB  - Bulgogi (Korean traditional barbecued beef) is the most well-known Korean food to
      foreigners. There are, however, few studies on its sensory characteristics and
      consumer acceptability. This study was performed to identify the sensory
      attributes of Bulgogi samples prepared with different formulation and to compare
      the consumer acceptability in Korea and the United States. Bulgogi samples were
      prepared with varying levels of sugar and soy sauce with/without garlic or sesame
      oil. Descriptive analysis was conducted by 8 trained panelists. In consumer
      tests, 42 consumers in Seoul, Korea, 53 consumers in Davis (Calif., U.S.A.), and
      39 consumers in St. Paul (Minn., U.S.A.) participated. Higher levels of sugar and
      soy sauce (SSS) significantly increased sweetness, saltiness, MSG taste, and soy
      sauce odor/flavor compared to the control made with the standard formula (CON).
      Elimination of sesame oil (ESO) significantly decreased sesame oil odor/flavor
      and oiliness, but increased green onion flavor. Elimination of garlic (EGC)
      significantly increased grilled beef odor/flavor, sesame oil odor/flavor, and
      oiliness, but decreased intensities of all the other attributes except
      bitterness. The consumers in Korea and the United States rated their overall
      liking for all samples similarly, preferring SSS to CON, EGC, and ESO. However
      Korean consumers seemed to detect the differences caused by formulation changes
      better than the U.S. consumers and these perceived differences seemed to impact
      the hedonic and the just-about-right ratings. Increase in soy sauce and sugar
      increased both Korean and the U.S. consumers' acceptability of Bulgogi, whereas
      eliminating garlic did not influence the consumer acceptability despite of its
      significant impact on sensory attributes. PRACTICAL APPLICATION: The food
      industry is increasingly interested in ethnic foods that satisfy sophisticated
      appetite of today's consumers. Korean cuisine is recently gaining popularity and
      perceived as "adventurous and spicy," appealing to researchers and marketers in
      the food industry worldwide. However, it is not easy to develop a new product
      based on ethnic cuisine because nonsensory factors, such as food neophobia and
      openness to new culture, can evoke adverse responses from the consumers. A
      systematic sensory approach can guide the product development by identifying both
      sensory and nonsensory factors affecting consumer acceptability. This study
      investigated sensory attributes of Bulgogi (Korean traditional barbecued beef),
      one of the most famous Korean foods, and compared consumer acceptability between
      Korea and the United States. The outcomes of this study, such as flavor profiles,
      consumer responses, evaluation procedure, and approaches taken for cross-cultural
      comparison, will provide the food industries with valuable information that will
      help to develop effective strategies for commercializing ethnic foods including
      recipe development for Bulgogi marinades.

PMID- 22417446
TI  - Industrially processed vacuum-packed peeled Kennebec potatoes: process
      optimization, sensory evaluation, and consumer response.
AB  - To optimize the processing and storage of Kennebec potatoes for sale in peeled,
      vacuum-packed ready-to-cook form, we studied the effects of blanching, various
      anti-browning solutions, and storage temperature. Unblanched potatoes pretreated
      with a mixture of 1% ascorbic acid and 0.5% citric acid, and stored at 2  degrees
      C, were found to have a shelf life of at least 1 mo without browning. Potatoes so
      treated differed sensorially from fresh potatoes, but were well received by
      consumers. PRACTICAL APPLICATION: The process described here maintains the
      characteristics of fresh potato with all the amenities of a processed product.

PMID- 22417447
TI  - Effects of cyclodextrin type on vitamin C, antioxidant activity, and sensory
      attributes of a mandarin juice enriched with pomegranate and goji berries.
AB  - The effects of the addition of cyclodextrins (CDs), beta-CD, or HP-beta-CD (1%),
      on the protection of antioxidant compounds of mandarin juices enriched with
      pomegranate extract and goji berries juice, was studied. Juices were prepared and
      after their thermal treatment (98  degrees C, 30 s) they were stored at 4 
      degrees C during 75 d. Vitamin C content, CIE L*a*b* color, antioxidant capacity,
      retinol equivalents, and sensory properties were studied. Losses on vitamin C
      were higher (6%) for juices with beta-CD than juices with HP-beta-CD. Retinol
      equivalents degradation was lower (3.4%) in juices with HP-beta-cyclodextrins
      than in those treated with beta-CD. Lower losses were observed for the
      instrumental and sensory color intensity in juices with HP-beta-CD addition.
      Finally, the antioxidant capacity was also higher in juices treated with HP-beta
      CD. Finally, the overall sensory quality of juices with HP-beta-CD was the best
      one after 30 d of cold storage. Even though beta-CD addition did not cause any
      improvement compared with control juice (without CD addition), the benefits of
      adding HP-beta-CD to this particular juice were shown in almost all parameters
      under study. PRACTICAL APPLICATION:  The present study deals with the practical
      aspects of the utilization of CDs and CD-complexes in the food industry. The
      molecular encapsulation of lipophilic food ingredients with CD are supposed to
      improve the stability of flavors, vitamins, colorants, and antioxidant activity,
      leading to extended product shelf life. The HP-beta-CD treated mandarin juice
      enriched with pomegranate extract and juice of goji berries will have a more
      intense color, higher vitamin C content, retinol equivalents, and antioxidant
      activity during storage and shelf life than control juices, with no CD addition.

PMID- 22417448
TI  - Internal quality and shelf life of eggs coated with oils from different sources.
AB  - Selected internal quality and shelf life of eggs coated with oils from
      differences sources (mineral oil, canola oil, corn oil, grape seed oil, olive
      oil, soybean oil, and sunflower oil) were evaluated during 5 wk of storage at 25 
      degrees C. As the storage time increased, weight loss increased whereas Haugh
      unit and yolk index values decreased. Throughout the 5 wk of storage, eggs coated
      with oils, regardless of oil sources, possessed better albumen and yolk quality
      than the control noncoated eggs. Oil coating minimized weight loss of eggs
      (<0.8%) compared with that (7.26%) of the noncoated eggs after 5 wk of storage at
      25  degrees C. No significant differences in internal quality (weight loss, Haugh
      unit, yolk index, and albumen pH) were generally observed among oil-coated eggs
      during 5 wk of storage. Based on the Haugh unit, the grade of noncoated eggs
      changed from AA at 0 wk to A at 1 wk and to B after 3 wk whereas that of oil
      coated eggs from AA at 0 wk to A at 4 wk and maintained A grade until 5 wk. This
      study demonstrated that oil coating, irrespective of oil sources, preserved the
      internal quality, minimized weight loss (<0.8%), and extended the shelf life of
      eggs by at least 3 wk longer than observed for the noncoated eggs at 25  degrees
      C storage. Soybean oil was a more practical option as a coating material for eggs
      due to its low cost. PRACTICAL APPLICATION: Eggs are highly perishable and
      susceptible to internal quality deterioration when stored above 7  degrees C.
      Refrigeration of eggs may be seldom practiced in some developing regions of the
      world. Therefore, an alternative method, that is inexpensive yet effective, to
      preserve the internal quality of eggs and to prevent microbial contamination is
      needed. Oil coating has been proven to preserve the internal quality, prolong
      shelf life, and minimize weight loss of eggs. This study demonstrated that,
      compared with other vegetable oils, soybean oil was a more practical option as a
      coating material for eggs during 5 wk of storage at 25  degrees C due to its low
      cost.

PMID- 22417449
TI  - Chemical, physical-chemical, and sensory characteristics of lychee (Litchi
      chinensis Sonn) wines.
AB  - Four lychee (Litchi chinensis Sonn) wines (prepared with 3 yeast strains [UFLA
      CA11, UFLA CA1183, and UFLA CA1174]) and a spontaneous fermentation (SPON) were
      done in order to add value to the fruit while preventing waste arising from the
      short shelf life of lychee. The fermentation was monitored daily by analyzing the
      soluble solids, pH, acidity, ethanol, and sugar. At the end of fermentation, the
      wines were subjected to chemical, physical-chemical, and sensory analysis. The
      wines prepared showed greater variations in the qualitative than in the
      quantitative analysis of their constituents. The sensory analysis indicated that
      the wines fermented by yeast UFLA CA1183 and UFLA CA11 had rates of acceptance
      above 75%. The principal components analysis separated the wines into 2 groups
      according to the analyzed compounds. Based on these analyses, the wine produced
      by inoculation with UFLA CA1183 proved to be the most suitable for the production
      of lychee wines. PRACTICAL APPLICATION: Development of new products and adding
      value to fruits. Importance of selection of specific yeasts for production of
      fruit wine.

PMID- 22417450
TI  - Sensory characteristics and consumer acceptance of bread and cracker products
      made from red or white wheat.
AB  - Whole grain consumption is being promoted due to a number of associated health
      benefits. However, whole grain consumption is below recommendations possibly due
      to the presence of characteristic flavors that consumers find unacceptable. The
      objective of this study was to investigate the sensory characteristics and
      consumer acceptance of products made from commercial whole grain flours produced
      from red or white wheats, and with fine or coarse bran particle sizes.
      Descriptive analysis and consumer acceptance panels were used to characterize
      both low (cracker) and intermediate (bread) moisture products made with the
      flours. Partial least squares (PLS) regression was used to correlate the
      descriptive and consumer data. Sensory differences in whole grain products made
      from red or white wheat with small or large bran particles sizes and product
      moisture contents were observed. Bran particle size had a greater effect on the
      sensory properties of the whole grain products, particularly within the cracker;
      conversely bran particle size had little influence on consumer acceptance. Red
      wheat products were found to be more acceptable than the white wheat products.
      However, a number of color * bran particle interactions were observed in both the
      descriptive and consumer data. PLS regression demonstrated that consumers could
      be divided into groupings based upon certain attributes and characteristics.

PMID- 22417451
TI  - Comparative effect of the addition of alpha-, beta-, or gamma-cyclodextrin on
      main sensory and physico-chemical parameters.
AB  - Although alpha-, beta-, and gamma-cyclodextrins (CDs) have been widely used to
      improve the color of different fruit juices, a comparative study of the effect of
      these natural CDs on other properties that also influence pear juice quality,
      such as odor and aroma, have not been reported yet. In this study, the
      comparative effect of the addition of alpha-, beta-, and gamma-cyclodextrin, the
      only CDs authorized to be used in the food industry by U.S. Food and Drug
      Administration (FDA) and European Union, on the pear juice quality was evaluated
      for the first time. Several instrumental and sensory properties of this fruit
      juice, such as color, volatile composition, odor, and aroma have been evaluated
      in the absence and presence of alpha-, beta-, and gamma-CD. A study of the aroma
      profile of pear juice showed that esters, aldehydes, alcohols, and terpenes were
      the most important chemical families. However, the addition of alpha-, beta-, and
      gamma-CD had different effects on both the concentration of individual volatile
      compounds and their chemical grouping. Furthermore, a trained sensory panel was
      used to evaluate color, overall odor, overall aroma, and overall quality of pear
      juice in the presence or absence of CDs. PRACTICAL APPLICATION: After comparing
      the effects of the addition of alpha-, beta-, and gamma-CD on pear juice, our
      final recommendation is to add alpha-CD (the natural CD formed by 6 units of
      glucose) to pear juice because it will significantly increase the global quality
      of the juice by reducing its browning but without producing a significant
      reduction in the aroma quality.

PMID- 22417452
TI  - Effects of starter culture and storage on the flavor of liquid whey.
AB  - The primary off flavors in dried whey proteins have been attributed to lipid
      oxidation products. A deeper understanding of lipid oxidation in fluid whey is
      crucial to understand how to minimize off flavors in dried whey protein. The
      objectives of this study were to further elucidate the role of storage and
      starter cultures as sources of lipid oxidation in whey. Fluid Cheddar,
      Mozzarella, and rennet-set wheys were manufactured from skim and whole milk.
      Liquid wheys and milks were evaluated by descriptive sensory and volatile
      instrumental analysis within 2 h of manufacture and following storage for 3 d at
      4  degrees C. Culture type greatly influenced the oxidative stability of liquid
      whey, with Cheddar and Mozzarella whey differing not only in sensory profile, but
      also in volatile compounds. The type of starter culture (Mozzarella compared with
      Cheddar) had more influence on flavor than the set type (acid compared with
      culture). Milks had lower relative abundances of volatile free fatty acids than
      their liquid whey counterparts. Volatile lipid oxidation products in wheys were
      higher than in their respective milks, but oxidation in both milks and wheys
      increased with storage time. Wheys from Cheddar starters displayed more oxidation
      products than wheys from Mozzarella starters. Starter media did not have an
      effect on the flavor or oxidative stability of liquid whey, however, culture
      strain influenced lipid oxidation of fluid whey. PRACTICAL APPLICATION: Lipid
      oxidation products are primary contributors to whey ingredient off-flavors.
      Flavor plays a critical and limiting role in widespread use of dried whey
      ingredients, and enhanced understanding of flavor and flavor formation in fluid
      whey are industrially relevant. Results from this study demonstrate that
      oxidation occurs in milk prior to cheesemaking but that starter type and starter
      strain influence also oxidative stability and lipid oxidation off flavors in
      fluid whey.

PMID- 22417455
TI  - Surgical nuances of clipping after coiling: looking beyond the international
      subarachnoid aneurysm trial.
AB  - After the introduction of Guglielmi Detachable Coils (GDC), endovascular
      management of ruptured and unruptured aneurysms became a viable alternative to
      surgical clipping as a "minimally invasive" option. Endovascular management of
      aneurysms became even more common after the International Subarachnoid Aneurysm
      Trial, which was one of the first prospective, randomized trials comparing
      clipping and coiling, showed reduced dependency and death in patients undergoing
      coiling after two months and one year. As the numbers of patients treated by
      endovascular therapy grow neurosurgeons are facing increasing challenges of
      clipping difficult aneurysms not suitable for coiling, including those that are
      wide-necked, thrombosed or involving many perforators. In addition, treatment
      failures (recurrent and residual aneurysms after coiling) pose difficult
      treatment scenarios fraught with complications due to surrounding adhesions, coil
      migration and involvement of adjacent neurovascular structures. Thus, we analyzed
      the recent literature dealing with the nuances of clipping after coiling and
      reviewed the current management principles involved in treating these difficult
      aneurysms.

PMID- 22417456
TI  - Increases in GroES and GroEL from Lactobacillus acidophilus L-92 in response to a
      decrease in medium pH, and changes in cytokine release from splenocytes:
      Transcriptome and proteome analyses.
AB  - To study the anti-allergy effects of probiotic Lactobacillus acidophilus L-92 (L
      92), changes in the immunomodulatory effect and key cell components in response
      to media pH in which L-92 cells were cultivated were studied using microarray and
      proteome analyses. Growth of L-92 cells was restricted if the medium pH was
      uncontrolled and the release of IL-12 from splenocytes increased as the pH
      decreased during cell growth. The decrease in pH from 5.0 to 4.5 at the
      exponential phase of growth had the greatest effect on the release of IL-12. When
      L-92 cells were cultured at low pH, the release of IL-12, IFN-gamma and IL-10 was
      increased but IL-4 release was decreased from splenocytes. Comparative
      transcriptome analysis between L-92 cells cultured at pH 5.0 and pH 4.5 in MRS
      medium revealed significant up-regulation of 121 genes and down-regulation of 92
      genes. Among the significantly changed genes, heat shock proteins such as GroES
      and GroEL were considered to be the most likely components affecting
      immunomodulation. Proteome analysis of the cell wall-associated components of L
      92 also supported increases in GroES and GroEL as cell surface components in L-92
      cells cultured at a lower pH. In conclusion, increases in cell wall-associated
      components of L-92, such as GroES and GroEL, in response to a pH decrease affect
      the release of certain cytokines from splenocytes.

PMID- 22417457
TI  - Rapid identification of Giardia duodenalis assemblages in NSW using terminal
      restriction fragment length polymorphism.
AB  - Humans are infected by 2 genetic assemblages (A and B) of Giardia duodenalis, a
      protozoan parasite that causes gastro-intestinal disease. Sub-assemblages AI,
      AII, BIII and BIV are commonly identified in human cases. Detection requires
      amplification of G. duodenalis loci. Subsequent DNA sequencing or restriction
      fragment length polymorphism (RFLP) identifies sub-assemblages but is expensive
      (DNA sequencing) or insensitive (RFLP). This study investigated a fluorescence
      based detection method, using terminal-restriction fragment length polymorphism
      (T-RFLP) of the glutamate dehydrogenase gene to characterize human infections.
      Clinical samples (n=73), positive for Giardia were collected in New South Wales,
      Australia, and were used to evaluate T-RFLP detection. The accuracy and
      sensitivity of T-RFLP detection was established by comparison to DNA sequencing
      and RFLP. Sub-assemblage assignment by T-RFLP identified BIV as the common
      subtype in N.S.W cases, whilst AI, AII and BIII were also detected. When compared
      to DNA sequencing and RFLP, analysis by T-RFLP was a reliable and reproducible
      method. Automated fluorescent detection enabled accurate sizing of restriction
      fragments and provided a sensitive alternative to RFLP. Discrimination of sub
      assemblages by T-RFLP was comparable to DNA sequencing, but was efficient and
      inexpensive. The protocol described here provides a rapid and sensitive
      diagnostic tool for routine sample screenings in epidemiological research.

PMID- 22417458
TI  - Photoluminescence brightening via electrochemical trap passivation in ZnSe and
      Mn(2+)-doped ZnSe quantum dots.
AB  - Spectroelectrochemical experiments on wide-gap semiconductor nanocrystals (ZnSe
      and Mn(2+)-doped ZnSe) have allowed the influence of trap electrochemistry on
      nanocrystal photoluminescence to be examined in the absence of semiconductor band
      filling. Large photoluminescence electrobrightening is observed in both materials
      upon application of a reducing potential and is reversed upon return to the
      equilibrium potential. Electrobrightening is correlated with the transfer of
      electrons into nanocrystal films, implicating reductive passivation of midgap
      surface electron traps. Analysis indicates that the electrobrightening magnitude
      is determined by competition between electron trapping and photoluminescence
      (ZnSe) or energy transfer (Mn(2+)-doped ZnSe) dynamics within the excitonic
      excited state, and that electron trapping is extremely fast (k(trap) ~ 10(11) s(
      1)). These results shed new light on the complex surface chemistries of
      semiconductor nanocrystals.

PMID- 22417459
TI  - The Q(y) absorption spectrum of the light-harvesting complex II as determined by
      structure-based analysis of chlorophyll macrocycle deformations.
AB  - The absorption spectrum of the main antenna complex of photosystem II, LHCII, has
      been modeled using, as starting points, the chlorophyll (chl) atomic coordinates
      as obtained by the LHCII crystal analysis [Liu, Z., Yan, H., Wang, K., Kuang, T.,
      Zhang, J., Gui, L., An, X., and Chang, W. (2004) Nature 428, 287-292] of three
      different trimers. The chl site Q(y) transition energies have been obtained in
      terms of the chl macrocycle deformations influencing the energy level of the chl
      frontier orbitals. Using these chl site transition energy values and the entire
      set of interaction energies, calculated in the ideal dipole approximation, the
      complete Hamiltonians for the three LHCII trimers have been written and the full
      set of 42 eigenstates of each LHCII trimer have been calculated. With the 42
      transition energies and transition dipole strengths, either unperturbed or
      associated to the eigenstates, the LHCII Q(y) absorption spectrum has been
      calculated using a chl absorption band shape. These calculations have been
      performed both in vacuo and in the presence of a medium. Despite the number of
      approximations, a good correlation with the measured absorption spectrum of a
      LHCII preparation is obtained. This analysis shows that, although a substantial
      C3 symmetry of the LHCII trimer in terms of both chl-chl distances and
      interaction energies is present, a marked variation among monomer subsets of site
      transition energies is estimated. This leads to a C3 symmetry breaking in the
      unperturbed chl site transition energies set and, consequently, in the trimer
      eigenstates. It is also concluded that interactions among chlorophylls do not
      significantly modify the light absorption role of LHCII in plant leaves.

PMID- 22417460
TI  - High-sensitivity C-reactive protein to detect metabolic syndrome in a centrally
      obese population: a cross-sectional analysis.
AB  - BACKGROUND: People with central obesity have an increased risk for developing the
      metabolic syndrome, type 2 diabetes and cardiovascular disease. However, a
      substantial part of obese individuals have no other cardiovascular risk factors,
      besides their obesity. High sensitivity C-reactive protein (hs-CRP), a marker of
      systemic inflammation and a predictor of type 2 diabetes and cardiovascular
      disease, is associated with the metabolic syndrome and its separate components.
      We evaluated the use of hs-CRP to discriminate between centrally obese people
      with and without the metabolic syndrome. METHODS: 1165 people with central
      obesity but without any previous diagnosis of hypertension, dyslipidemia,
      diabetes or cardiovascular disease, aged 20-70 years, underwent a physical
      examination and laboratory assays to determine the presence of the metabolic
      syndrome (NCEP ATP III criteria). Multivariable linear regression analyses were
      performed to assess which metabolic syndrome components were independently
      associated with hs-CRP. A ROC curve was drawn and the area under the curve was
      calculated to evaluate whether hs-CRP was capable to predict the presence of the
      metabolic syndrome. RESULTS: Median hs-CRP levels were significantly higher in
      individuals with central obesity with the metabolic syndrome (n = 417; 35.8%)
      compared to individuals with central obesity without the metabolic syndrome (2.2
      mg/L (IQR 1.2-4.0) versus 1.7 mg/L (IQR 1.0-3.4); p < 0.001). Median hs-CRP
      levels increased with an increasing number of metabolic syndrome components
      present. In multivariable linear regression analyses, waist circumference and
      triglycerides were the only components that were independently associated with hs
      CRP after adjusting for smoking, gender, alcohol consumption and the other
      metabolic syndrome components. The area under the ROC curve was 0.57 (95%-CI 0.53
      0.60). CONCLUSIONS: Hs-CRP has limited capacity to predict the presence of the
      metabolic syndrome in a population with central obesity.

PMID- 22417461
TI  - Magical numbers.

PMID- 22417462
TI  - There's hope in the valley.
AB  - Aboriginal women in the remote Fitzroy Valley region in Western Australia's
      Kimberley were concerned about high rates of alcohol use in pregnancy and its
      possible impact on child development. They successfully lobbied for restricted
      access to alcohol in 2007. In 2009 they developed a strategy for the diagnosis
      and prevention of Fetal Alcohol Spectrum Disorders (FASD) and the support of
      parents and carers of affected children. Aboriginal organisations then partnered
      with research and clinical groups from Sydney to conduct a FASD prevalence study.
      This commenced in 2010 following extensive community consultation and receipt of
      community consent. Data from this study are still being collected and will be
      used by the community to advocate for improved services and new models of health
      care. Prevention of FASD is important to optimise health and development for
      future generations of Aboriginal children and to ensure the transfer of culture
      and language from one generation to the next.

PMID- 22417463
TI  - Accuracy of weight perception, life-style behaviours and psychological distress
      among overweight and obese adolescents.
AB  - AIM: To compare overweight and obese adolescents with accurate and inaccurate
      self-reported weight perception across a range of behaviours and measures of
      psychological well-being. METHODS: This study uses a cross-sectional survey of
      grade 7-12 high school students in New South Wales, Australia, conducted in 2008
      (n= 7553). Overweight and obese students based on body mass index were classified
      as accurate perceivers (weight perception was 'too fat') or inaccurate perceivers
      (weight perception was 'about right'). RESULTS: Nearly a third of adolescents had
      incongruity between self-perceived body weight status and body mass index
      determined weight category. Compared with boys, girls were less likely to
      underestimate their body weight (odds ratio: 0.26; 95% confidence interval: 0.25,
      0.27) and more likely to overestimate their body weight (odds ratio: 3.4; 95%
      confidence interval: 3.3, 3.5). Accurate body weight perception was higher in
      obese adolescents compared with overweight adolescents (69.5% vs. 44.0%).
      Compared with mis-perceivers, accurate overweight and obese perceivers had
      significantly higher odds of trying to lose weight and being more physically
      active; however, they showed a combination of unhealthy and healthy behaviours
      (i.e. dietary patterns and sedentary activities). Accurate weight perception
      among overweight and obese adolescents was associated with increased odds of
      feeling sad or depressed in the past 6 months. CONCLUSIONS: Further research on
      social, familial and psychological factors that predict or mediate healthy and
      unhealthy weight-related behaviours among adolescents by accuracy of weight
      perception is needed. Accurate weight perception should be considered in
      counselling and behavioural interventions.

PMID- 22417464
TI  - Evidence to support current use of nebulised epinephrine in croup to achieve
      immediate clinical improvement.

PMID- 22417465
TI  - Rice bodies in juvenile idiopathic arthritis: a clinical image.

PMID- 22417467
TI  - Antibiotic treatment of acute otitis media in children: which schedule to follow?

PMID- 22417468
TI  - Importance of the genital examination to screen for Klinefelter syndrome among
      obese children and adolescents.

PMID- 22417469
TI  - St Anthony's fire: an unusual presentation.

PMID- 22417470
TI  - A life without pain: congenital insensitivity to pain due to compound
      heterozygous SCN9A mutation.

PMID- 22417471
TI  - Insight. Photos showing austistic child's preoccupation with lines and angles,
      and his interest in details over gestalt.

PMID- 22417472
TI  - Website review: Healthy children.

PMID- 22417473
TI  - A case of ant anaphylaxis.
AB  - A four-year-old girl developed anaphylaxis following ant stings at her parent's
      property in country New South Wales. The offending insect was identified by an
      entomologist as the green head ant. Ant sting anaphylactic reactions in
      Australia, the importance of identifying the offending insect following sting
      anaphylaxis and the signs of insect sting anaphylaxis are further discussed.

PMID- 22417474
TI  - Unusual cause of neonatal rectal bleeding: colonic intramural haematoma.
AB  - Bright rectal bleeding in a neonate is most commonly due to necrotising
      enterocolitis, gastrointestinal infection or cows milk protein intolerance. We
      present here an infant who developed PR bleeding after cardiac surgery. Bleeding
      persisted despite presumptive treatment for the most common causes. A colonic
      intramural haematoma was identified on colonoscopy most likely related to
      anticoagulation in the setting of cardiac surgery.

PMID- 22417475
TI  - Body image trends among Icelandic adolescents: a cross-sectional national study
      from 1997 to 2010.
AB  - The aim of this study was to evaluate trends in body image among Icelandic
      adolescents from 1997 to 2010. Data from five cross-sectional surveys conducted
      among national samples of 9th and 10th graders in Iceland using five time points
      (1997, 2000, 2006, 2009, and 2010) were compared to examine changes in body
      image. In total, 32,397 adolescents participated in the study. Body image among
      14-15-year-old adolescents in Iceland improved significantly over the 13-year
      period. Girls reported more negative body image than boys at all time points.
      However, the positive change in body image from 1997 to 2010 was more pronounced
      for girls than boys, resulting in a narrower gap between the genders. The current
      results are encouraging and indicate that in an age of increased overweight and
      obesity, the body image of Icelandic adolescents is becoming more positive.

PMID- 22417476
TI  - Pulmonary emboli from therapeutic sodium hyaluronate.
AB  - A patient presented with shortness of breath and pleuritic pain shortly after
      bilateral knee synovial injections with sodium hyaluronate (HA). He was
      discharged after a brief hospitalization without a diagnosis when no Doppler or
      radiologic evidence of deep vein thrombosis or pulmonary  emboli was found.
      Radiologic studies found patchy ground glass opacities that were predominantly
      peripheral in disposition, with prominent septal lines in the lungs; a subsequent
      pulmonary function test showed a reduced diffusing capacity of the lung for
      carbon monoxide (D(LCO)).  These results prompted a lung biopsy that revealed
      multiple emboli composed of HA and fibrin in medium size pulmonary arteries,
      enlarged lymphatic vessels, and a bone marrow embolus. This is the first report
      of HA emboli following therapeutic HA injections and demonstrates that pulmonary
      function  tests can be used to infer the reduction in pulmonary vascular area
      consequent to pulmonary emboli, and so can contribute to the detection of
      pulmonary emboli in unusual presentations.

PMID- 22417478
TI  - Angiotensin-I converting enzyme inhibitory and antioxidant activities of egg
      protein hydrolysates produced with gastrointestinal and nongastrointestinal
      enzymes.
AB  - Egg is a well-known rich source of bioactive peptides. In this study, egg protein
      (egg white and egg yolk proteins) hydrolysates were produced with
      gastrointestinal enzymes (pepsin and pancreatin) or nongastrointestinal enzymes
      (thermolysin and alcalase), and fractionated by ultrafiltration and cation
      exchange chromatography. Angiotensin-I converting enzyme (ACE) inhibitory and
      antioxidant activities, amino acid composition and molecular weight distribution
      were studied, and the physicochemical properties were related with the
      bioactivities. Our results showed that egg protein hydrolysates produced with non
      GI enzymes (thermolysin and alcalase) showed significantly higher ACE inhibitory
      activity, whereas similar or even lower antioxidative activities, than those of
      hydrolysates produced with GI enzymes. ACE-inhibitory activity significantly
      correlated with the amino acid composition, especially the proportion of
      positively charged amino acid, whereas antioxidant activities correlated with the
      proportion of low molecular weight peptides under 500 Da. Understanding the
      relationship between the bioactivities and physicochemical properties of the
      hydrolysates/fractions is important to facilitate the development technologies
      for preparing fractions with improved bioactivities.

PMID- 22417479
TI  - Moisture-induced aggregation of alpha-lactalbumin: effects of temperature,
      cations, and pH.
AB  - Alpha-lactalbumin is an important dairy protein ingredient, and has been widely
      used in high-protein foods such as infant formula and nutritional bars for its
      nutritional and functional properties. The purpose of this study was to
      investigate the moisture-induced aggregation of alpha-lactalbumin in premixed
      protein dough model systems, and to illustrate the effects of temperature,
      cations, and pH on the progress of protein aggregation. Our results suggested
      that storage temperature was a critical factor for protein aggregation in model
      systems, and the formation of protein aggregates became faster with increases in
      storage temperature. Calcium significantly improved the thermal stability of
      alpha-lactalbumin and slowed down the formation of protein aggregates. The
      increases in pH accelerated the aggregation of alpha-lactalbumin. Our results
      also suggested that the formation of intermolecular disulfide bonds together with
      noncovalent interactions are the main mechanisms resulting in the moisture
      induced aggregation of alpha-lactalbumin in model systems. PRACTICAL APPLICATION:
      Alpha-lactalbumin is an important dairy protein ingredient, and has been widely
      used in high-protein foods such as infant formula and nutritional bars for its
      nutritional and functional properties. Our results suggested low storage
      temperature, the presence of calcium and low pH condition can make high-protein
      food products containing alpha-lactalbumin more stable.

PMID- 22417477
TI  - Sex differences in primary hypertension.
AB  - Men have higher blood pressure than women through much of life regardless of
      race and ethnicity. This is a robust and highly conserved sex difference that it
      is also observed across species including dogs, rats, mice and chickens and it is
      found in induced, genetic and transgenic animal models of hypertension. Not only
      do the differences between the ovarian and testicular hormonal milieu contribute
      to this sexual dimorphism in blood pressure, the sex chromosomes also play a role
      in and of themselves. This review primarily focuses on epidemiological studies of
      blood pressure in men and women and experimental models of hypertension in both
      sexes. Gaps in current knowledge regarding what underlie male-female differences
      in blood pressure control are discussed. Elucidating the mechanisms underlying
      sex differences in hypertension may lead to the development of anti-hypertensives
      tailored to one's sex and ultimately to improved therapeutic strategies for
      treating this disease and preventing its devastating consequences.

PMID- 22417480
TI  - Toward the antioxidant and chemical characterization of mycorrhizal mushrooms
      from northeast Portugal.
AB  - Mushrooms are widely appreciated all over the world for their nutritional
      properties and pharmacological value as sources of important bioactive compounds.
      Mycorrhizal macrofungi associate with plant roots constituting a symbiotic
      relationship. This symbiosis could influence the production of secondary
      metabolites, including bioactive compounds. We focused on the evaluation of
      antioxidant potential and chemical composition of mycorrhizal mushrooms species
      from Northeast Portugal: Amanita caesarea, Amanita muscaria, Amanita pantherina,
      Chroogomphus fulmineus, Cortinarius anomalus, Cortinarius collinitus, Cortinarius
      violaceus, Lactarius quietus, Lactarius volemus, Russula sardonia, Suillus
      luteus, and Tricholoma ustale. A similar profile of metabolites was observed in
      the studied species with the order sugars > fat > ascorbic acid > phenolic
      compounds > tocopherols. Nevertheless, the samples revealed different
      compositions: prevalence of sugars in L. volemus, fat and ascorbic acid in A.
      muscaria, phenolic compounds in C. anomalus and tocopherols, and antioxidant
      activity in S. luteus. PRACTICAL APPLICATION: Chemical characterization of 12
      mycorrhizal mushrooms was achieved. They are sources of nutraceuticals, such as
      sugars and fatty acids, and contain bioactive compounds, such as vitamins and
      phenolic acids. Edible species can be incorporated in diets as sources of
      antioxidants, while nonedible species can be explored as sources of bioactive
      metabolites.

PMID- 22417481
TI  - Effect of annatto seed and coriander leaves as natural antioxidants in fish
      meatballs during frozen storage.
AB  - The effects of annatto (0.1 g/100g) and coriander (0.5 g/100g) were assessed
      against lipid oxidation in white hake meatballs cooked in boiling water (95 +/- 1
      degrees C) for 30 min and stored at -18  degrees C for 120 d. The fatty acids
      (FA) and the nutritional quality, cholesterol, cholesterol oxides, thiobarbituric
      acid reactive substances (TBARS) values, and conjugated dienes were analyzed to
      follow the course of oxidation. Annatto and coriander were efficient in the
      control of lipid oxidation, also preserving the essential FA. At 120 d of
      storage, the eicosapentaenoic acid (EPA) concentration decreased respectively by
      43%, 32%, 12%, and 9% in the control, coriander, annatto, and annatto + coriander
      patties. For docosahexaenoic acid (DHA), these concentrations decreased,
      respectively, 44%, 30%, 11%, and 7%, revealing a probable synergistic effect
      among the antioxidant compounds present in both spices. On the other hand,
      annatto and coriander were not able to act protecting the meatballs against lipid
      oxidation when they were cooked, also not exerted any effect in the cholesterol
      oxidation. PRACTICAL APPLICATION: Spices, especially coriander and annatto, can
      be an alternative to substitute synthetic additives with antioxidants to prevent
      loss of important unsaturated fatty acids (UFA) in fish meatballs during frozen
      storage for 120 d. The maximum effect was observed when 0.5% coriander and 0.1%
      annatto were used in combination. Cooking did not induce the formation of
      cholesterol oxides, compounds that can cause more health damages than cholesterol
      itself; however, during storage the cholesterol oxides levels presented a little
      increase regardless of spice addition.

PMID- 22417482
TI  - Color of whole-wheat foods prepared from a bright-white hard winter wheat and the
      phenolic acids in its coarse bran.
AB  - The color of wheat kernels often impacts the color and thereby the value of wheat
      based foods. A line of hard white winter wheat (B-W HW) with bright appearing
      kernels has been developed at the Kansas State Agricultural Research Center. The
      objective of this study was to compare the color of several foods made from the B
      W HW wheat with those of 2 hard white wheat cultivars, Trego and Lakin. The B-W
      HW kernels showed higher lightness (L*, 57.6) than Trego (55.5) and Lakin (56.8),
      and the increased lightness was carried over to its bran and whole-wheat flour.
      Alkaline noodle and bread crumb made from the B-W HW whole-wheat flour showed
      slightly higher lightness (L*) than those made from Trego and Lakin. The sum of
      soluble and bound phenolics extracted from the 3 wheat brans, which had not been
      preextracted to remove lipids, was found to be 17.22 to 18.98 mg/g. The soluble
      phenolic acids in the brans were principally vanillic, ferulic, and syringic. The
      bound phenolic acids in the brans were dominated by ferulic, which accounted for
      50.1% to 82.2% of total identified bound phenolic acids. Other bound phenolic
      acids were protocatechuic, caffeic, syringic, trans-cinnamic, p-hydroxybenzoic, p
      coumaric, and vanillic. The lightness (L*) values of coarse wheat brans
      correlated positively with their levels of bound protocatechuic (r = 0.72, P <
      0.01) and p-hydroxybenzoic acids (r = 0.75, P < 0.01).

PMID- 22417483
TI  - Process improvement for semipurified oleosomes on a pilot-plant scale.
AB  - Semipurified oleosomes were isolated on a pilot-plant scale using improved
      process extraction conditions. The improved process consisted of continuous
      centrifugation in a three-phase decanter with recirculation of slurry until most
      of the oleosomes were recovered. Oleosome fractionation, oleosin identification,
      and isoflavone and saponin mass distributions and recoveries were investigated.
      The improved pilot-plant oleosome extraction process was achieved in 8 h. A total
      of 91%+/- 1% of soybean oil was recovered as intact oleosomes. The oil content of
      the aqueous supernatant and the residue fractions were low at 2% and 3%,
      respectively. The aqueous supernatant fraction contained 40% total soybean
      protein. About 76% of the proteins present in the oleosome fraction were soybean
      storage proteins. Washing the semipurified oleosomes with a 0.1 M Tris-HCl, pH
      8.6 containing 0.4 M sucrose, and 0.5 M NaCl resulted in the recovery of the
      associated storage proteins. The recovery of these proteins in addition to the
      protein in aqueous supernatant accounted for 79% of the total soybean storage
      proteins fractionated by this process. Oleosins were detected at 17 and 18 kDa.
      Isoflavones and saponins partitioned into the oleosome, aqueous supernatant, and
      residue fractions at different ratios with the majority, about 82 and 63 mole%,
      respectively, in oleosome and aqueous supernatant fractions, making these
      fractions an attractive source for phytochemicals.

PMID- 22417484
TI  - Flavonol content in the water extract of the mulberry (Morus alba L.) leaf and
      their antioxidant capacities.
AB  - The biological activities of the mulberry (Morus alba L.) leaf have been
      attributed to its flavonoid content. The water extract of the mulberry leaf
      (WEML) was prepared by autoclaving at 121  degrees C for 15 min, and the flavonol
      content of the WEML was determined by HPLC The WEML contained 4 flavonols in the
      following order: quercetin-3-beta-D-glucose (QT-G) > quercetin-3-O-glucose-6"
      acetate (QT-GA) > rutin (RT) > quercetin (QT). In the oxygen radical absorbance
      capacity (ORAC) assay, QT had the highest peroxyl radical-scavenging capacity and
      a similar hydroxyl radical-scavenging capacity as its glycosides (QT-G, QT-GA,
      and RT). QT exhibited a stronger cellular antioxidant capacity (CAC) against 2,2'
      Azobis(2-amidinopropane) dihydrochloride (AAPH)- and Cu2+-induced oxidative
      stress in HepG2 cells compared to its glycosides, indicating that the
      intracellular antioxidant capacity of QT and its glycosides may depend upon both
      the permeability across the cell membrane and the peroxyl or hydroxyl radical
      scavenging capacity. PRACTICAL APPLICATION: The information presented might be
      used for developing mulberry leaf-based functional foods.

PMID- 22417485
TI  - Effect of extrusion on the antioxidant capacity and color attributes of expanded
      extrudates prepared from purple potato and yellow pea flour mixes.
AB  - Foods with antioxidant capacity provide protection against cardio-vascular,
      certain forms of cancers, and Alzheimer's diseases caused by oxidative damages
      and contribute health benefits. The effect of extrusion cooking on the
      antioxidant capacity and color attributes of extruded products prepared from 3
      selected formulations of purple potato and yellow pea flours using a co-rotating
      twin screw extruder were studied. Expansion ratios of the extruded products
      varied from 3.93 to 4.75. The total antioxidant capacities (TAC) of the extruded
      products, using DPPH assay, were 3769 to 4116 MUg trolox equivalent/g dry weight
      sample and not significantly different (P > 0.05) from their respective raw
      formulations. The total phenolic contents (TP) of the extruded products varied
      from 2088 to 3766 MUg of gallic acid equivalent/g dry weight sample and retained
      73% to 83% of the TP from the raw formulations after extrusion. The total
      anthocyanins contents (TA) in the extrudates were 0.116 to 0.228 mg of malvidin-3
      glucosides/g dry weight sample. Compared with their raw formulations, significant
      losses (60% to 70%) of the TA in the extruded products occurred due to extrusion
      cooking. Browning indices and color attributes such as brightness, chroma, and
      hue angle agreed with degradation of anthocyanins in the extruded products.
      However, extrusion cooking retained antioxidant capacities of the raw
      formulations in the extruded products either in their natural forms or degraded
      products with radical scavenging activity. This study demonstrated the potential
      for the production of puffed extruded food products with the improved antioxidant
      content from colored potatoes and pulse formulations.

PMID- 22417486
TI  - Influence of heating on the polyphenolic content and antioxidant activity of
      grape seed flour.
AB  - The production of grape seed flour (GSF) from a waste product generated during
      winemaking, is of interest in product development applications due to its
      potential health benefits. However, before GSF can used in baking as a source of
      additional antioxidants, research on its heat stability is required. The overall
      objective of this study was to assess changes in phenolic content and antioxidant
      activity of GSF during heating. Merlot GSF was heated at 5 temperatures (120 to
      240  degrees C) for 0 to 90 min. At each time/temperature combination, total
      phenolic content (TPC), total flavanoid content (TFC), Trolox equivalent
      antioxidant capacity (TEAC), 2,2 diphenyl-1-picrylhydrazyl (DPPH) radical
      scavenging, and ferric ion reducing antioxidant power (FRAP) of the extracts were
      determined. Specific polyphenolic compounds, including catechin, gallocatechin,
      epicatechin, and gallic acid were also measured. Results showed that when Merlot
      GSF was heated to >=180  degrees C, significant decreases in the TPC and
      antioxidant activity, measured using FRAP, DPPH, and TEAC, were observed. Longer
      heating times also caused a reduction in antioxidant capability. Catechin and
      epicatechin content decreased with increasing heating temperature while
      gallocatechin and gallic acid content increased. Both catechin and epicatechin
      content had strong positive correlations (r > 0.91) with TPC and TFC, as well
      with FRAP and TEAC, suggesting that the GSF antioxidant activity is related to
      the presence of these particular compounds. Overall, while a decrease in
      antioxidant content was observed during heating, this occurred at higher baking
      temperatures. Thus GSF may be suitable for use as an ingredient in baked goods to
      bolster antioxidant content. PRACTICAL APPLICATION: In order for Merlot grape
      seed flour (GSF) to be used in baking as a source of additional antioxidant
      compounds, the impact of heating on the polyphenolic compounds in the GSF needed
      to be examined. Thermal treatment of Merlot GSF caused significant decreases in
      the TPC, antioxidant power, and specific polyphenolic compounds when heated >=180
      degrees C. Thus while antioxidant content decreased with higher heating
      temperatures, this occurred at higher baking temperatures. Thus, GSF may be
      suitable for use as an ingredient in baked goods to bolster antioxidant content.

PMID- 22417487
TI  - A gas chromatography-tandem quadrupole mass spectrometric analysis of
      policosanols in commercial vegetable oils.
AB  - Reportedly policosanols (PCs) have various beneficial functionalities on health.
      A gas chromatography-tandem mass spectrometry (GC-MS/MS) with a low limit of
      detection (LOD), and high specificity, recovery, and precision was successfully
      established for the PC analysis in vegetable oils. The LODs for the PCs were in
      the range of 0.002 to 0.016 MUg/mL. The relative standard deviation (RSD) for the
      repeated analysis of PCs was less than 3.356%. The mean recoveries for spiked
      heptacosanol and octacosanol in vegetable oil were 102.3% and 106.3%,
      respectively. The total PC contents in the vegetable oils varied from 3.01 to
      427.83 mg/kg oil. Perilla seed, grape seed, and rice bran oils were found to be
      highly rich sources of PCs, containing 427.83, 245.15, and 171.17 mg PCs/kg oil,
      respectively. Corn, sesame, and soybean oils contained only a negligible quantity
      of PCs. The PC composition in vegetable oils was greatly source dependent. In
      perilla seed oil, octacosanol was the single most predominant component,
      representing 55.93% of the total PC. In grape seed oil, however, hexacosanol is
      the most abundant PC, followed by octacosanol, tetracosanol, and triacontanol in
      a decreasing order. The major PCs in rice bran oil were triacontanol,
      octacosanol, hexacosanol, and tetracosanol, which constituted over 87.3% of the
      total PC. This represents the 1st report on the composition and contents of PC in
      most vegetable oils analyzed here. PRACTICAL APPLICATION: The information might
      be used for the development of vegetable oil products with beneficial
      functionality.

PMID- 22417488
TI  - A rapid LC/MS/MS method for the analysis of nonvolatile antiinflammatory agents
      from Mentha spp.
AB  - Mints (Mentha spp.), aromatic crops grown largely for their essential oils, also
      are rich sources of nonvolatile antiinflammatory agents. Identification and
      quantitation of the constituents responsible for their antiinflammatory activity
      is challenging owing to the lack of suitable chromatographic methodology. In the
      present research, the simultaneous quantitation of antiinflammatory constituents
      rosmarinic acid, oleanolic acid, and ursolic acid in mints was attained by using
      a unique tandem HPLC column system coupled with an electrospray ionization mass
      detection (MRM mode). The ion mode optimization for rosmarinic acid under
      negative and triterpenoid acids under positive was achieved by setting 2 time
      segments in a single run where the polarity mode was switched from negative (0 to
      10 min) to positive (10 to 40 min). For the investigated concentration ranges of
      antiinflammatory agents in mints, good linearities (r2 >= 0.998) were obtained
      for each calibration curve. Validation of precision and accuracy for this method
      showed that intra- and inter-day repeatabilities for all analytes were less than
      5.51%, and the recoveries varied from 97.8% to 99.3%. The developed LC/MS/MS
      assay provides a suitable quality control method for the determination of
      antiinflammatory constituents in Mentha spp. There is a wide range of diversity
      in the natural product composition for these acids across the Mentha germplasm
      collection evaluated. The presence of these antiinflammatory acids in post
      distilled mints shows that value-added nutraceutical enriched products can be
      developed with proper processing and recovery systems in addition to the
      distillation and capture of the valuable volatile essential oils. PRACTICAL
      APPLICATION: Results from this research would benefit both commercial farmers
      growing mint for essential oil and those in the food industry where value-added
      phytopharmaceutical enriched products can be developed with proper processing,
      quality control, and recovery systems during mint essential oil distillation.

PMID- 22417489
TI  - Lipid and cholesterol oxidation in chicken meat are inhibited by sage but not by
      garlic.
AB  - The effects of the addition of sage and garlic in chicken meat on lipid and
      cholesterol oxidation, having as prooxidant factors the addition of salt, thermal
      treatment, and frozen storage, were evaluated. The content of unsaturated fatty
      acids did not change in the presence of sage; on the contrary, with garlic, the
      content of these fatty acids decreased after cooking and storage. Hexanal and
      pentanal contents were lower in patties containing sage, and higher in those with
      garlic. The 7-ketocholesterol was the cholesterol oxide found in higher amount in
      raw chicken on day 0, while the formation of 7beta- and 7alpha-hydroxycholesterol
      was verified only from day 30 on. Cooking and storage resulted in increase of
      total cholesterol oxides and decrease of alpha- and gamma-tocopherol. Sage was
      effective in controlling lipid and cholesterol oxidation, minimizing the
      prooxidant effects of salt, cooking, and storage. However, garlic presented no
      effect as antioxidant and accelerated lipid oxidation. PRACTICAL APPLICATION: The
      addition of sage to chicken meat (0.1 g/100 g) is a good alternative to prevent
      and delay the formation of compounds derived from lipid oxidation that are
      responsible for off-flavors and loss of nutritional quality during long-term
      frozen storage. Care must be taken when using garlic to seasoning chicken meat
      products, such as hamburgers and meatballs, especially cooked or precooked due to
      its potential to promote lipid oxidation and consequently raising the risk of
      having the product rejected by the consumer.

PMID- 22417490
TI  - Abrasive stripping square-wave voltammetry of blackberry, raspberry, strawberry,
      pomegranate, and sweet and blue potatoes.
AB  - Electro-oxidation potentials of 7 fruits and vegetables were determined by
      abrasive stripping voltammetry. The responses were characterized by 2 peaks with
      maxima at 0.45 and 0.55 V compared with Ag/AgCl, respectively. Both electrode
      reactions appear reversible at a frequency of 8 Hz. They can be ascribed to
      anthocyanidins and ellagic acid as electroactive compounds. By this method, an
      antioxidative capacity of a certain plant can be quickly estimated without
      extraction of active components.

PMID- 22417491
TI  - Phenolic acid composition and antioxidant properties of Malaysian honeys.
AB  - The phenolic acid and flavonoid contents of Malaysian Tualang, Gelam, and Borneo
      tropical honeys were compared to those of Manuka honey. Ferric
      reducing/antioxidant power assay (FRAP) and the 1,1-diphenyl-2-picryl-hydrazyl
      (DPPH) radical-scavenging activities were also quantified. All honey extracts
      exhibited high phenolic contents (15.21 +/- 0.51- 42.23 +/- 0.64 mg/kg),
      flavonoid contents (11.52 +/- 0.27- 25.31 +/- 0.37 mg/kg), FRAP values (892.15 +/
      4.97- 363.38 +/- 10.57 MUM Fe[II]/kg), and high IC50 of DPPH radical-scavenging
      activities (5.24 +/- 0.40- 17.51 +/- 0.51 mg/mL). Total of 6 phenolic acids
      (gallic, syringic, benzoic, trans-cinnamic, p-coumaric, and caffeic acids) and 5
      flavonoids (catechin, kaempferol, naringenin, luteolin, and apigenin) were
      identified. Among the Malaysian honey samples, Tualang honey had the highest
      contents of phenolics, and flavonoids, and DPPH radical-scavenging activities. We
      conclude that among Malaysian honey samples, Tualang honey is the richest in
      phenolic acids, and flavonoid compounds, which have strong free radical
      scavenging activities.

PMID- 22417492
TI  - Oxygen consumption rate of permeabilized cells and isolated mitochondria from
      pork M. masseter and liver examined fresh and after freeze-thawing at different
      pH values.
AB  - The oxygen consumption rate (OCR) of 2 types of permeabilized tissues and their
      corresponding isolated mitochondria from porcine M. masseter and liver, resulting
      in 4 systems, was studied at different pH values (5.0 to 7.1) using fresh samples
      and samples frozen directly in liquid nitrogen (N2) or air-frozen at -20 degrees
      C. A protocol with the additive sequence rotenone-succinate-ADP (adenosine
      diphosphate)-cytochrome c-FCCP (carbonyl cyanide p
      trifluoromethoxyphenylhydrazone) was used to study respiration changes. The OCR
      of liver respiring on succinate (OCR(S)) was higher than that of muscle tissue.
      pH had a larger effect on OCR(S) than freeze-thawing. Low pH was associated with
      reduced OCR(S). The OCR(S) of isolated muscle mitochondria appeared to be an
      underestimated relative to the OCR(S) of permeabilized muscle cells. Increasing
      pH, following prior subjection to pH 5.0, showed partial reversibility of the
      OCR(S). The freeze-thaw cycle increased the OCR(S) when muscle systems were
      frozen and examined above pH 6.0; this effect was less apparent for liver tissue.
      A response to cytochrome c addition, indicating a defective outer mitochondrial
      membrane, was observed for all 4 systems. The response was, however, lowest for
      permeabilized cells. The ADP/FCCP additive pair indicated partial coupling for
      isolated liver and muscle mitochondria. These additives gave weak responses for
      the permeabilized liver cells while the OCR seemed to be inhibited for
      permeabilized muscle fibers when ADP/FCCP was added. PRACTICAL APPLICATION: The
      mitochondrial state is believed to be important for myoglobin reduction,
      development of flavor, and possibly other meat qualities. By monitoring the
      oxygen consumption in mitochondria and meat we can better understand and control
      such processes following freezing and thawing.

PMID- 22417493
TI  - Stability of anthocyanins in frozen and freeze-dried raspberries during long-term
      storage: in relation to glass transition.
AB  - Anthocyanins, natural plant pigments in the flavonoid group, are responsible for
      the red color and some of the nutraceutical benefits of raspberries. This study
      explores anthocyanin degradation in frozen and freeze-dried raspberries during
      storage in relation to glass transition temperatures. Frozen raspberries were
      stored at -80, -35, and -20  degrees C, while freeze-dried raspberries were
      stored at selected water activity (a(w)) values ranging from 0.05 to 0.75 at room
      temperature (23  degrees C) for more than a year. The characteristic glass
      transition temperatures (T'(g)) of raspberries with high water content and glass
      transition temperature (T(g)) of raspberries with small water content were
      determined using a differential scanning calorimeter. The pH differential method
      was used to determine the quantity of anthocyanins in frozen and freeze-dried
      raspberries at selected time intervals. The total anthocyanins in raspberries
      fluctuated during 378 d of storage at -20 and -35, and -80  degrees C.
      Anthocyanin degradation in freeze-dried raspberries ranged from 27% to 32% and
      78% to 89% at a(w) values of 0.05 to 0.07 and 0.11 to 0.43, respectively, after 1
      y. Anthocyanins were not detectable in freeze-dried raspberries stored at a(w)
      values of 0.53 to 0.75 after 270 d. First order and Weibull equations were used
      to fit the anthocyanin degradation in freeze-dried raspberries. The 1(st)-order
      rate constant (k) of anthocyanin degradation ranged from 0.003 to 0.023 days-1 at
      the selected water activities. Significant anthocyanin degradation occurred in
      both the glassy and rubbery states of freeze-dried raspberries during long-term
      storage. However, the rate of anthocyanin degradation in freeze-dried raspberries
      stored in the glassy state was significantly smaller than the rate of anthocyanin
      degradation in the rubbery state.

PMID- 22417494
TI  - Quality comparison of continuous steam sterilization segmented-flow aseptic
      processing versus conventional canning of whole and sliced mushrooms.
AB  - This study was carried out to investigate segmented-flow aseptic processing of
      particle foods. A pilot-scale continuous steam sterilization unit capable of
      producing shelf stable aseptically processed whole and sliced mushrooms was
      developed. The system utilized pressurized steam as the heating medium to achieve
      high temperature-short time processing conditions with high and uniform heat
      transfer that will enable static temperature penetration studies for process
      development. Segmented-flow technology produced a narrower residence time
      distribution than pipe-flow aseptic processing; thus, whole and sliced mushrooms
      were processed only as long as needed to achieve the target F0  = 7.0 min and
      were not overcooked. Continuous steam sterilization segmented-flow aseptic
      processing produced shelf stable aseptically processed mushrooms of superior
      quality to conventionally canned mushrooms. When compared to conventionally
      canned mushrooms, aseptically processed yield (weight basis) increased 6.1% (SD =
      2.9%) and 6.6% (SD = 2.2%), whiteness (L) improved 3.1% (SD = 1.9%) and 4.7% (SD
      = 0.7%), color difference (DeltaE) improved 6.0% (SD = 1.3%) and 8.5% (SD =
      1.5%), and texture improved 3.9% (SD = 1.7%) and 4.6% (SD = 4.2%), for whole and
      sliced mushrooms, respectively. Segmented-flow aseptic processing eliminated a
      separate blanching step, eliminated the unnecessary packaging of water and
      promoted the use of bag-in-box and other versatile aseptic packaging methods.
      PRACTICAL APPLICATION: Segmented-flow aseptic processing is capable of producing
      shelf stable aseptically processed particle foods of superior quality to a
      conventionally canned product. This unique continuous steam sterilization process
      eliminates the need for a separate blanching step, reduces or eliminates the need
      for a liquid carrier, and promotes the use of bag-in-box and other versatile
      aseptic packaging methods.

PMID- 22417495
TI  - Characterization and evaluation of the Ag+-loaded soy protein isolate-based
      bactericidal film-forming dispersion and films.
AB  - This study aims to prepare bactericidal films developed from soy protein isolate
      (SPI) based film-forming dispersions (FFDs) for use in the food and medical
      fields. The FFD and films were prepared after the incorporation of different
      concentrations of AgNO3 as a bactericidal agent. The transparency, tensile
      strength, and antimicrobial features were evaluated. Structural characterizations
      were also performed by Fourier transform infrared spectroscopy, scanning electron
      microscope, and atomic force microscopy analysis. Results showed that the opacity
      of these FFD was greatly decreased after the incorporation of AgNO3. The SPI-5
      film has the largest tensile strength (P < 0.05) compared with that of the other
      ones. Micro structural imaging analysis showed an increase in the surface
      irregularities with the addition of AgNO3. The minimum inhibitory concentration
      of AgNO3 was 336 MUg/mL FFD for both Escherichia coli ATCC 25923 and
      Staphylococcus aureus ATCC 25922. The SPI-AgNO3 films developed from the FFD with
      the minimal AgNO3 concentration at 336 MUg/mL FFD also showed bactericidal
      effects for both the strains. These results may prove promising for the use of
      SPI-AgNO3 films in the food or medical industries. PRACTICAL APPLICATION: The
      films prepared in this study are biodegradable and will be used in medical and
      food fields.

PMID- 22417496
TI  - Physical changes in white and brown rice during simulated gastric digestion.
AB  - Previous studies have shown that brown rice generates lower glycemic responses
      than white rice, a trait that may be beneficial in the dietary management of
      chronic diseases such as diabetes and hyperlipidemia. The objective of this study
      was to investigate influence of rice digestion on the physical properties of the
      gastric digesta that may further impact intestinal absorption. A dynamic stomach
      model, human gastric simulator, was used to simulate the gastric digestion of
      white and brown rice. The pH, solids content, and rheological properties of the
      gastric digesta, as well as the size distribution of particles were studied.
      Static soaking was conducted to reveal the changes in moisture absorption and
      texture in rice kernels during simulated gastric digestion, as affected by
      shaking and the acid in gastric juice. Magnetic resonance imaging (MRI) was used
      to image the diffusion of gastric juice into the rice kernels. The results
      indicate that the bran layer on brown rice had a profound effect in digestion, as
      it inhibited the absorption of moisture and acid leading to decreased texture
      degradation, thus delaying the rice disintegration as well as dissolution and
      slowing emptying of solids. MRI is effective in exhibiting the diffusion of
      gastric juice as affected by gastric acid and the influence of bran. This study
      provided quantitative evidence regarding the manner in which structural
      differences between white and brown rice affect their gastric digestion.
      PRACTICAL APPLICATION: The study presented in this paper focuses on how the
      structural differences in white and brown rice affect their gastric digestion.
      This information may help consumers to better understand the health benefits
      associated with eating brown rice.

PMID- 22417497
TI  - High-speed weight estimation of whole herring (Clupea harengus) using 3D machine
      vision.
AB  - Weight is an important parameter by which the price of whole herring (Clupea
      harengus) is determined. Current mechanical weight graders are capable of a high
      throughput but have a relatively low accuracy. For this reason, there is a need
      for a more accurate high-speed weight estimation of whole herring. A 3
      dimensional (3D) machine vision system was developed for high-speed weight
      estimation of whole herring. The system uses a 3D laser triangulation system
      above a conveyor belt moving at a speed of 1000 mm/s. Weight prediction models
      were developed for several feature sets, and a linear regression model using
      several 2-dimensional (2D) and 3D features enabled more accurate weight
      estimation than using 3D volume only. Using the combined 2D and 3D features, the
      root mean square error of cross-validation was 5.6 g, and the worst-case
      prediction error, evaluated by cross-validation, was +/-14 g, for a sample (n =
      179) of fresh whole herring. The proposed system has the potential to enable high
      speed and accurate weight estimation of whole herring in the processing plants.
      PRACTICAL APPLICATION: The 3D machine vision system presented in this article
      enables high-speed and accurate weight estimation of whole herring, thus enabling
      an increase in profitability for the pelagic primary processors through a more
      accurate weight grading.

PMID- 22417498
TI  - Extrusion and characterization of thermoplastic starch sheets from "macho"
      banana.
AB  - Starch isolated from macho banana was oxidized by using 2.5% and 3.5% (w/w) of
      sodium hypochlorite. Native and oxidized starches with glycerol were processed
      using a conical twin screw extruder to obtain thermoplastic laminates or sheets,
      which were partially characterized. Oxidized banana starches presented higher
      moisture and total starch but lower ash, protein, lipids, and apparent amylose
      content than the native starch. Micrographs of sheets from oxidized starches
      showed wrinkles and cavities presumably caused by the plasticizer, but with less
      free glycerol and unplasticized starch granules than those from native starch.
      Sheets from oxidized starch showed a notorious increase in all thermal parameters
      (To, Tp, and DeltaH), mechanical properties (tensile strength, elongation at
      break, and elasticity), and solubility. Banana starch X-ray diffraction patterns
      corresponded to a mixture of the A- and B-type polymorphs, with apparently
      slightly higher crystallinity in oxidized specimens than in native starch. A
      similar trend was observed in the corresponding sheets. PRACTICAL APPLICATION:
      Due to the pollution problem caused by the conventional plastics, there has been
      a renewed interest in biodegradable sheets, because they may have the potential
      to replace conventional packaging materials. Banana starch might be an
      interesting raw material to be used as edible sheet, coating or in food
      packaging, and preservation, because it is biodegradable, cheap, innocuous, and
      abundant.

PMID- 22417499
TI  - Characterization of water distribution in xanthan-curdlan hydrogel complex using
      magnetic resonance imaging, nuclear magnetic resonance relaxometry, rheology, and
      scanning electron microscopy.
AB  - Xanthan-curdlan hydrogel complex (XCHC) has been shown capable of retaining
      moisture up to 5 freeze-thaw cycles (FTCs); however, moisture distribution in the
      complex in relation to the hydrogel composition and structure remains
      uncharacterized. In the present study, magnetic resonance imaging (MRI), nuclear
      magnetic resonance (NMR) relaxometry, rheology, and scanning electron microscopy
      (SEM) were used to examine the effect of water distribution and interaction with
      2.0% aqueous solutions of xanthan, curdlan, and XCHC consisting of equal amounts
      of both polysaccharides. A gel structure with an indication of syneresis was
      clearly seen in the MR image of curdlan alone, whereas the distribution of
      protons throughout xanthan and XCHC samples remained homogeneous and showed no
      detectable syneresis. The three-dimensional network, indicated by frequency
      sweeps, of curdlan was responsible for curdlan's gel structure. The frequency
      sweep and slope of the storage modulus (G') of XCHC was significantly closer to
      curdlan with higher elasticity and less dependency upon angular frequency than
      xanthan alone. The reduction in XCHC dynamic moduli (G' and G") compared to
      curdlan could be attributed to the formation of wavy layers instead of a fully
      cured three-dimensional structure. Addition of xanthan to curdlan restricted XCHC
      spin-spin relaxation time (T2) to intermediate and slower exchange regimes,
      namely approximately 110 and 342 ms, respectively, promoting the polymer's
      interaction with water while inhibiting interpolymer interactions found in
      curdlan. A 3rd proton pool with the slowest T2 seen in curdlan was not found in
      XCHC, correlating to the absence of syneresis. PRACTICAL APPLICATION: The
      combination of texture measurements and discrete noninvasive techniques was found
      capable of providing insightful understanding of water distribution in a gel
      system. These techniques may be applied to other hydrogel complexes. The XCHC
      system investigated has the potential to enhance freeze-thaw stability in frozen
      food products by minimizing syneresis due to undesirable temperature fluctuations
      during distribution and consumer application.

PMID- 22417500
TI  - Oil migration in chocolate and almond product confectionery systems.
AB  - Oil migration from high oil content almond confections into adjacent chocolate
      causes changes in product quality. The objective of this study was to quantify
      the oil migration from almond products to dark chocolate. Magnetic resonance
      imaging (MRI) was used to monitor spatial and temporal changes of liquid lipid
      content. A multislice spin echo pulse (MSSE) sequence was used to acquire images
      with a 7.8-ms echo time and a 1000-ms repetition time using a 1.03T Aspect AI MRI
      spectrometer. Samples were prepared as a 2-layer model system of chocolate and
      almond confection. Six different almond products and 1 type of dark chocolate
      were used. Samples were stored at 20, 25, and 30 degrees C for a time frame of
      several months. Rate and extent of migration were quantified by a kinetic
      expression based on the linear dependence of oil uptake by chocolate and the
      square root of the time. Samples showed distinctly different rate and extent of
      oil migration, as evidenced by quantitative differences in the kinetic rate
      constants and equilibrium uptake for the different sample types. This work will
      be helpful to design formulations for almond and almond-based products in
      confections. PRACTICAL APPLICATION: This work will be helpful to design
      formulations for almond use in confections.

PMID- 22417501
TI  - Digestibility, fermentability, and energy value of highly cross-linked phosphate
      tapioca starch in men.
AB  - The objective of this study was to determine glycemic and breath hydrogen
      responses in 10 healthy men in response to highly cross-linked starch phosphate
      (HXLS), made of tapioca starch (TS). Plasma glucose concentration was analyzed at
      baseline and at 30, 60, 90, 120, 150, and 180 min postprandially. In addition,
      breath hydrogen excretion was measured at baseline and at hourly intervals, over
      10 h, after test substance challenge. When compared with unmodified TS easily
      digested, the area under the curve of plasma glucose of HXLS was 64% smaller, and
      was almost the same as that of microcrystalline cellulose. When compared with
      fructo-oligosaccharide rapidly fermented by the microbial bacteria, the area
      under the excretion curve of breath hydrogen gas of HXLS was 93% smaller, and was
      almost the same as that of water only. These results show that HXLS is harder to
      digest and ferment than unmodified TS in men.

PMID- 22417502
TI  - Enhanced antiviral activity of soybean beta-conglycinin-derived peptides by
      acylation with saturated fatty acids.
AB  - Peptide mixtures prepared from soybean beta-conglycinin (7S-peptides) were
      acylated with saturated fatty acids of different chain length (6C-18C) in order
      to improve their antiviral activity against Feline calicivirus (FCV) strain F9
      which is a typical norovirus surrogate. Among the fatty acids varieties, it was
      revealed that 7S-peptides acylated with myristic and palmitic acids potently
      inhibited FCV replication. Myristorylation and palmitoylation of 7S-peptides kept
      host cells viability at 91.51% and 98.90%, respectively. The infectivity of FCV
      on Crandell-Reese feline kidney cells was further determined after exposure of
      initial titer of 10(6.47) TCID50/mL. Myristoylated and palmitoylated 7S-peptides
      significantly (P < 0.006) reduced FCV infectivity as compared to native 7S
      peptides. Native 7S-peptides showed 25% FCV inhibitory activity while
      myristoylated and palmitoylated 7S-peptides exhibited 98.59% and 99.98% reduction
      in FCV infectivity, respectively. Myristoylated and palmitoylated 7S-peptides
      demonstrated higher anti-FCV activity in a wide range of concentration with
      complete reduction at 25 MUg/mL. Surface hydrophobicity was significantly (P <
      0.05) increased after attachment of long hydrocarbon fatty acids to 7S-peptides
      as supported by changes in fluorescence intensity. Enzymatic hydrolysis together
      with acylation will give an insight into surface and physiological functional
      lipopeptides derived from soy beta-conglycinin.

PMID- 22417503
TI  - Effects of high-voltage electrostatic fields on the quality of tilapia meat
      during refrigeration.
AB  - Fresh fish is typically brought to market refrigerated at approximately 4 
      degrees C, R-storage. A storage method has been devised that combines
      refrigeration with a high-voltage electrostatic field (100 kV/m; E-storage). It
      was developed to improve the quality and prolong the shelf life of foods. This
      study investigated changes in the freshness of tilapia meat under E-storage
      conditions. The total viable count of tilapia reached 107 CFU/g on the 7th d of
      refrigeration in R-storage. By the 6th d, K-value had increased from 20% to 61.7%
      for E-storage and to 94.7% for R-storage. Volatile basic nitrogen had increased
      from 12.54 mg/100 g to about 24.34 and 25.03 mg/100 g for R- and E-storage (on
      the 7th and 10th d), respectively. The sensory assessment also indicated that E
      storage yielded an improvement in quality over that of R-storage. Practical
      application of the study model has the potential to prolong the freshness of
      fish.

PMID- 22417504
TI  - Survival of Salmonella Typhi and Shigella dysenteriae in dehydrated infant
      formula.
AB  - Powdered infant formula has previously been linked to the transmission of various
      bacterial pathogens in infants resulting in life-threatening disease and death.
      Survival studies of 2 common foodborne pathogens, Salmonella enterica serovar
      Typhi and Shigella dysenteriae, in powdered infant formula have not been
      previously studied despite the potentially devastating consequences from
      ingestion of these organisms, particularly by newborns, in case of a natural or
      deliberate contamination event. Therefore, to better predict the risk of S. Typhi
      and S. dysenteriae infection from consumption of infant formula, the present
      study was undertaken to determine survival of these microorganisms in dry infant
      formula under varying atmospheric conditions. A 2-strain cocktail of S. Typhi and
      a 3-strain cocktail of S. dysenteriae were stored for up to 12 wk in dehydrated
      infant formula in an ambient air or nitrogen atmosphere. Viable counts of S.
      Typhi at 12 wk in infant formula revealed a 2.9- and 1.69-log decrease in ambient
      air and nitrogen atmosphere, respectively. Viable counts of S. dysenteriae at 12
      wk in infant formula revealed a 0.81- and 0.42-log decrease in ambient air and
      nitrogen atmosphere, respectively. These results show that S. Typhi and S.
      dysenteriae can remain viable for prolonged periods of time in powdered infant
      formula, and the presence of nitrogen enhances survival. PRACTICAL APPLICATION:
      Our goal in this work was to study the survival of S. Typhi and S. dysenteriae in
      dehydrated storage conditions in infant formula. This interest is partially
      generated by the possibility of using these 2 microorganisms to deliberately
      contaminate the food supply. The outcome of this study will help us to have a
      better idea how to respond and react to the risk of deliberate food
      contamination.

PMID- 22417505
TI  - Utilization of African grains for sourdough bread making.
AB  - Acha and Iburu flours were singly subjected to sourdough fermentation with
      previously selected autochthonous starters. Sourdoughs were used (30%, wt/wt) as
      aroma carriers and acidifiers during short time fermentation with the addition of
      baker's yeast. Acha and Iburu sourdough breads were compared to wheat sourdough
      bread started with the same strains and to breads made with the same formula but
      using baker's yeast alone. During Acha and Iburu sourdough fermentations, starter
      lactic acid bacteria reached almost the same cell density found in wheat
      sourdoughs. Acidification was more intense. Iburu sourdough bread had the highest
      total titratable acidity, the lowest pH, and contained the highest levels of free
      amino acids and phytase activity. The values of in vitro protein digestibility
      did not differ between Acha sourdough and wheat sourdough breads, while Iburu
      sourdough bread showed a slightly lower value. Acha and Iburu sourdough breads
      showed lower specific volume and higher density with respect to wheat sourdough
      breads. Nevertheless, Acha and Iburu sourdough breads were preferred for hardness
      and resilience. As shown by sensory analysis, Acha and especially Iburu sourdough
      breads were appreciated for color, acid taste and flavor, and overall
      acceptability. PRACTICAL APPLICATION: This study was aimed at evaluating the
      technological and nutritional properties of the African cereals Acha and Iburu.
      Sourdough fermentation and the use of selected starters increased the nutritional
      and sensory qualities and the potential application for bakery industry.

PMID- 22417506
TI  - Prolonging the viability of Lactobacillus plantarum through the addition of
      prebiotics into the medium.
AB  - This article reports on the effects of prebiotics on the growth/death kinetics,
      metabolism, and biomass production by 2 strains of Lactobacillus plantarum (c19
      and DSMZ 2601, isolated from table olives and purchased from a Public Collection,
      respectively). The research was divided into 3 different steps, in order to
      highlight the optimal combination for cell viability and experiments were
      performed under the conditions of an accelerated shelf life test; thus, 3
      combinations were pointed out (fructooligosaccharides [FOS], 5 g/L; glucose +
      inulin, 2.5 + 2.5 g/L; glucose + FOS, 2.5 + 2.5 g/L). A sample containing only
      glucose was used as control. The results highlighted that the 3 combinations
      aforementioned prolonged cell viability over the time both under low and high
      inoculum conditions (3 and 9 log CFU/mL, respectively); however, FOS alone caused
      a reduction of biomass production, even if cell number was not affected by this
      compound. Therefore, as a final result of this research, the combination glucose
      + FOS could be proposed as a suitable mean to achieve an optimal production of
      biomass and prolong cell viability over the time. PRACTICAL APPLICATION: Food
      producers require a prolonged viability of probiotic bacteria in functional
      foods; this goal is usually achieved by refrigeration. In this article, the
      prolongation of cell viability through the addition of prebiotics was proposed.

PMID- 22417507
TI  - Microbial ecology studies of spontaneous fermentation: starter culture selection
      for prickly pear wine production.
AB  - A procedure for designing starter cultures for fermentation is illustrated for
      prickly pear wine production. The illustration includes kinetic studies on
      inoculated and spontaneous fermentation, microorganism identification studies
      based on molecular biology tools, and microbial ecology studies, which led to the
      selection of strains that are capable of synthesizing alcohol and desirable
      volatile compounds. Results show that a mixed starter inoculum containing Pichia
      fermentans and Saccharomyces cerevisiae leads to a fermented product that
      contains 8.37% alcohol (v/v). The gas chromatography and mass spectrometry (GC
      MS) analysis shows the presence of 9 major volatile compounds (Isobutanol,
      Isopentanol, Ethyl acetate, Isoamyl acetate, Ethyl octanoate, Ethyl decanoate,
      Ethyl 9-decanoate, beta-Phenylethyl acetate, and Phenylethyl alcohol) that have
      ethereal, fruity, aromatic notes that are considered to be essential for a fine
      wine flavor. These compounds harmonically synergize with the alcohol to produce a
      fermented product with a unique flavor and taste. Several assays using the mixed
      culture show that the process is stable, predictable, controllable, and
      reproducible. Moreover, the results show that a mixed culture leads to a broader
      range of aromatic products than that produced by a single, pure culture.
      Therefore, we conclude that combinations of Saccharomyces strains and non
      Saccharomyces strains can be used to obtain high-quality fermented beverages from
      prickly pear juice.

PMID- 22417508
TI  - Efficacy of slightly acidic electrolyzed water in killing or reducing Escherichia
      coli O157:H7 on iceberg lettuce and tomatoes under simulated food service
      operation conditions.
AB  - The objective of this study was to evaluate the efficacy of slightly acidic
      electrolyzed (SAEO) water in killing or removing Escherichia coli O157:H7 on
      iceberg lettuce and tomatoes by washing and chilling treatment simulating
      protocols used in food service kitchens. Whole lettuce leaves and tomatoes were
      spot-inoculated with 100 MUL of a mixture of 5 strains of E. coli O157:H7.
      Washing lettuce with SAEO water for 15 s reduced the pathogen by 1.4 to 1.6 log
      CFU/leaf, but the treatments did not completely inactivate the pathogen in the
      wash solution. Increasing the washing time to 30 s increased the reductions to
      1.7 to 2.3 log CFU/leaf. Sequential washing in SAEO water for 15 s and then
      chilling in SAEO water for 15 min also increased the reductions to 2.0 to 2.4 log
      CFU/leaf, and no cell survived in chilling solution after treatment. Washing
      tomatoes with SAEO water for 8 s reduced E. coli O157:H7 by 5.4 to 6.3 log
      CFU/tomato. The reductions were increased to 6.6 to 7.6 log CFU/tomato by
      increasing the washing time to 15 s. Results suggested that application of SAEO
      water to wash and chill lettuce and tomatoes in food service kitchens could
      minimize cross-contamination and reduce the risk of E. coli O157:H7 present on
      the produce. PRACTICAL APPLICATION: SAEO water is equally or slightly better than
      acidic electrolyzed (AEO) water for inactivation of bacteria on lettuce and
      tomato surfaces. In addition, SAEO water may have the advantages over AEO water
      on its stability, no chlorine smell, and low corrosiveness. Therefore, SAEO water
      may have potential for produce wash to enhance food safety.

PMID- 22417509
TI  - Volatile trans-2-hexenal, a soybean aldehyde, inhibits Aspergillus flavus growth
      and aflatoxin production in corn.
AB  - Trans-2-hexenal, a volatile aldehyde, is produced by soybean (Glycine max [L.]
      Merr) and other plants via the lipoxygenase pathway. In vitro tests showed it
      significantly (P < 0.001) reduced Aspergillus flavus germinating conidial
      viability at 10 MUM, with approximately 95% viability reduction observed at 20
      MUM. The viability of nongerminated conidia was not reduced. To test the
      effectiveness of this volatile to prevent fungal growth in stored corn, trans-2
      hexenal was pumped intermittently into glass jars containing corn. Experiments
      were performed to determine the ability of 2 different pump cycle time-courses to
      prevent A. flavus growth on sterile corn (23% moisture). Intermittently (30-min
      pumping period) over 7 d, this volatile was pumped through 350 g of corn kernels
      inoculated with 1 mL of 3 * 104 conidia of A. flavus. Controls consisted of (1)
      sterile corn, (2) corn inoculated with A. flavus with no pumped air, and (3) corn
      inoculated with A. flavus with intermittently pumped air. Aflatoxin B1 (AFB1),
      viability counts, and aldehyde concentration in the headspace were performed in
      each experiment. To determine whether an increased time period between volatile
      pumping would prevent A. flavus growth, a 2nd series of experiments were
      performed that were similar to the 1st series except that trans-2-hexenal (only)
      was pumped for a 30-min period every 12 h. Experiments were performed 3 times for
      each time course. Both experiments showed that intermittent pumping of volatile
      trans-2-hexenal significantly (P < 0.001) prevented A. flavus growth and
      aflatoxin B1 production over a 7-d period. PRACTICAL APPLICATION: Results from
      this study indicate that intermittent pumping of volatile trans-2-hexenal could
      be used to protect stored corn from A. flavus growth and aflatoxin contamination.

PMID- 22417510
TI  - Antibacterial activity and mechanism of action of chlorogenic acid.
AB  - In this study, the antibacterial activity and mechanism of action of chlorogenic
      acid against bacteria were assessed. The data from minimum inhibitory
      concentration (MIC) values showed that chlorogenic acid effectively inhibited the
      growth of all tested bacterial pathogens, and the MIC values were ranging from 20
      to 80 MUg/mL. An investigation into action mode of chlorogenic acid against the
      pathogen indicated that chlorogenic acid significantly increased the outer and
      plasma membrane permeability, resulting in the loss of the barrier function, even
      inducing slight leakage of nucleotide. The leakage of cytoplasmic contents was
      also observed by electron micrographs. These results supported our hypothesis
      that chlorogenic acid bound to the outer membrane, disrupted the membrane,
      exhausted the intracellular potential, and released cytoplasm macromolecules,
      which led to cell death.

PMID- 22417511
TI  - The effect of calcinated calcium and chlorine treatments on Escherichia coli
      O157:H7 87-23 population reduction in radish sprouts.
AB  - The effect of calcinated calcium spray on Escherichia coli O157:H7 87-23
      population reduction during radish sprout production was studied. Artificially
      inoculated radish seeds were soaked in sodium hypochlorite (NaOCl) solutions (200
      and 20000 ppm), rinsed in distilled water, and sprayed with water or a calcinated
      calcium solution during sprouting. Microbial plate count was obtained at each
      step of the process and germination rate was determined after 72 h of sprouting.
      Scanning electron microscopy (SEM) was done on treated seeds and sprouts to
      locate which parts were populated by the E. coli cells. The results showed that
      the active compound in the calcinated calcium was calcium oxide. The treatment of
      200 ppm NaOCl soaking followed by 0.04% calcinated calcium spray resulted in no
      microbial growth after a 72-h sprouting, while maintaining a high germination
      rate. The 0.4% calcinated calcium spray significantly reduced the germination
      rate and is therefore not recommended. Soaking the seeds in a 20000 ppm chlorine
      solution achieved the highest E. coli count reduction (1.65 log CFU/g). However,
      the E. coli cells that survived the 20000 ppm chlorine soak grew to 6 log CFU/g
      sprouts after a 72-h sprouting, significantly higher than the initial count on
      the seeds. The SEM microimages showed that the bacteria were mostly located in
      the roots of the radish sprouts and all across the seed surface. The E. coli
      O157:H7 87-23 cells appeared to be located in biofilms or embedded into the
      radish sprout tissues during sprouting. PRACTICAL APPLICATION: The seed
      sanitation treatment with 20000 ppm chlorine solution that is currently used by
      the sprout industry was once again found to be ineffective in eliminating
      inoculated pathogenic cells. More importantly, the remaining cells that have
      survived the chlorine wash would grow during sprouting to reach an alarmingly
      high cell concentration. The new observation of E. coli cells and sprout tissue
      interaction manifested as embedding of the cells in sprout tissues, if confirmed,
      will have a significant impact on the microbial safety intervention strategies
      used in the sprout industry. This research demonstrated the importance of
      eliminating all pathogens on the seeds before germination and sprouting.

PMID- 22417512
TI  - Maintenance of safety and quality of refrigerated ready-to-cook seasoned ground
      beef product (meatball) by combining gamma irradiation with modified atmosphere
      packaging.
AB  - Meatballs were prepared by mixing ground beef and spices and inoculated with E.
      coli O157:H7, L. monocytogenes, and S. enteritidis before packaged in modified
      atmosphere (3% O2 + 50% CO2 + 47% N2) or aerobic conditions. The packaged samples
      were irradiated at 0.75, 1.5, and 3 kGy doses and stored at 4  degrees C for 21
      d. Survival of the pathogens, total plate count, lipid oxidation, color change,
      and sensory quality were analyzed during storage. Irradiation at 3 kGy
      inactivated all the inoculated (approximately 106 CFU/g) S. enteritidis and L.
      monocytogenes cells in the samples. The inoculated (approximately 106 CFU/g) E.
      coli O157:H7 cells were totally inactivated by 1.5 kGy irradiation. D10-values
      for E. coli O157:H7, S. enteritidis, and L. monocytogenes were 0.24, 0.43, and
      0.41 kGy in MAP and 0.22, 0.39, and 0.39 kGy in aerobic packages, respectively.
      Irradiation at 1.5 and 3 kGy resulted in 0.13 and 0.36 mg MDA/kg increase in 2
      thiobarbituric acid-reactive substances (TBARS) reaching 1.02 and 1.49 MDA/kg,
      respectively, on day 1. Irradiation also caused significant loss of color and
      sensory quality in aerobic packages. However, MAP effectively inhibited the
      irradiation-induced quality degradations during 21-d storage. Thus, combining
      irradiation (3 kGy) and MAP (3% O2 + 50% CO2 + 47% N2) controlled the safety risk
      due to the potential pathogens and maintained qualities of meatballs during 21-d
      refrigerated storage. PRACTICAL APPLICATION: Combined use of gamma irradiation
      and modified atmosphere packaging (MAP) can maintain quality and safety of
      seasoned ground beef (meatball). Seasoned ground beef can be irradiated at 3 kGy
      and packaged in MAP with 3% O2 + 50% CO2 + 47% N2 gas mixture in a high barrier
      packaging materials. These treatments can significantly decrease risk due to
      potential pathogens including E. coli O157:H7, L. monocytogenes, and S.
      enteritidis in the product. The MAP would reduce the undesirable effects of
      irradiation on quality, and extend the shelf life of the product for up to 21 d
      at 3  degrees C.

PMID- 22417513
TI  - Extracts of edible and medicinal plants in inhibition of growth, adherence, and
      cytotoxin production of Campylobacter jejuni and Campylobacter coli.
AB  - Campylobacter spp. is recognized as one of the most common cause of food-borne
      bacterial gastroenteritis in humans. Campylobacter infection causes
      campylobacteriosis, which can range from asymptomatic to dysentery-type illnesses
      with severe complications, such as Guillian-Barre syndrome. Epidemiological
      studies have revealed that consumption of poultry products is an important risk
      factor of this disease. Adherence and cytotoxic activity of the bacteria to host
      mucosal surfaces have been proposed to be critical steps in pathogenesis.
      Innovative tools for controlling Campylobacter, such as natural products from
      plants, represent good alternatives for use in foods or as therapeutic agents. In
      this study, 28 edible or medicinal plants species were analyzed for their
      bactericidal effects on the growth of Campylobacter jejuni and C. coli. The
      extracts of Acacia farnesiana, Artemisia ludoviciana, Opuntia ficus-indica, and
      Cynara scolymus were the most effective against these microorganisms at minimal
      bactericidal concentrations (MBCs) of 0.3, 0.5, 0.4, and 2.0 mg/mL, respectively.
      No effect on growth was detected with lower concentrations of extract (25%, 50%,
      or 75% of the MBC) added to the media. The effect of each extract (75% of the
      MBC) on adherence and cytotoxicity of C. jejuni and C. coli was evaluated in Vero
      cells. Adherence of Campylobacter to Vero cells was significantly affected by all
      the extracts. Cytotoxic activity of bacterial cultures was inhibited by A.
      farnesiana and A. ludoviciana. These plant extracts are potential candidates to
      be studied for controlling Campylobacter contamination in foods and the diseases
      associated with this microorganism. PRACTICAL APPLICATION: Innovative tools for
      controlling Campylobacter, such as natural products from plants, represent good
      alternatives for use in foods or as therapeutic agents. The extracts of Acacia
      farnesiana, Artemisia ludoviciana, Opuntia ficus-indica, and Cynara scolymus were
      the most effective against these microorganisms. Adherence and cytotoxic activity
      of the bacteria to host mucosal surfaces which are critical steps in pathogenesis
      were decreased by these extracts. Our results point to these plants as potential
      candidates for the control of Campylobacter contamination in foods, the treatment
      of the diseases associated with this microorganism, and as feed supplements to
      reduce on-farm prevalence of Campylobacter.

PMID- 22417515
TI  - Acid resistance and verocytotoxin productivity of enterohemorrhagic Escherichia
      coli O157:H7 exposed to microwave.
AB  - We examined the acid resistance and verocytotoxin (VT) productivity of
      enterohemorrhagic Escherichia coli O157:H7 irradiated by microwave with a
      domestic microwave oven and a commercial microwave radiator equipped with a
      thermo-regulator. When the cell suspension (5 mL) chilled at 0  degrees C was
      treated with a domestic microwave oven at weak power (2.45 GHz, 100 W) for 60 s,
      the living cell number was reduced by 2 orders (final temperature, about 65 
      degrees C). The surviving cells showed lower acid resistance and VT productivity
      than nonirradiated cells. To examine the nonthermal effect of microwave on acid
      resistance and VT productivity, the cells in Luria-Bertani medium were
      intermittently irradiated to keep the culture temperature at 37  degrees C with
      the microwave radiator (2.45 GHz, 0.6 W/mL). The intermittent radiation slightly
      reduced the acid resistance, but clearly suppressed the VT productivity.
      Microwave oven is probably useful for reducing not only the living cell number
      but also the acid resistance and VT productivity of EHEC O157:H7.

PMID- 22417514
TI  - Activity of citrus essential oils against Escherichia coli O157:H7 and Salmonella
      spp. and effects on beef subprimal cuts under refrigeration.
AB  - Escherichia coli O157:H7 and Salmonella spp. are bacterial pathogens often
      associated with beef, and cause many cases of foodborne illness each year in the
      United States. During beef slaughter and processing, these bacteria may spread
      from the hide or intestines to the carcass. The objective of this research was to
      investigate the use of naturally occurring compounds citrus essential oils (CEOs)
      extracted from orange peel to reduce or eliminate these pathogens at the chilling
      stage of processing, or during fabrication. Brisket flats (used to simulate beef
      subprimals) were spot inoculated with approximately 6 log of surrogate generic E.
      coli cocktail (previously shown to be identical in growth and survival parameters
      to E. coli O157:H7 and Salmonella spp.). Following drying, CEOs were applied by
      spraying at concentrations of 3% and 6% to the surface of different pieces of
      meat. Treatments were applied using a custom built spray cabinet at 2.07 bar and
      applied at a rate of 3.79 L/min to replicate commercial practices. The CEOs
      significantly reduced (P < 0.05) the concentration of E. coli on the brisket
      flats in comparison to inoculated no spray or water sprayed controls over a
      period of 90 d, while causing an initial reduction of approximately 1.4 log
      units. Total aerobic bacteria and psychrotrophic counts were also reduced on
      uninoculated briskets following treatment. These results indicate that 3% cold
      pressed terpeneless Valencia orange oil could be used as an additional
      intervention against E. coli O157:H7 and Salmonella spp. at the refrigerated
      storage stage of processing. PRACTICAL APPLICATION: CEOs are natural compounds
      that have been designated as Generally Recognized as Safe (GRAS). They can be
      used to control Salmonella spp. and E. coli O157:H7 on beef carcasses at the
      chilling stage.

PMID- 22417516
TI  - Probabilistic models for the prediction of target growth interfaces of Listeria
      monocytogenes on ham and turkey breast products.
AB  - This study developed growth/no growth models for predicting growth boundaries of
      Listeria monocytogenes on ready-to-eat cured ham and uncured turkey breast slices
      as a function of lactic acid concentration (0% to 4%), dipping time (0 to 4 min),
      and storage temperature (4 to 10  degrees C). A 10-strain composite of L.
      monocytogenes was inoculated (2 to 3 log CFU/cm2) on slices, followed by dipping
      into lactic acid and storage in vacuum packages for up to 30 d. Total bacterial
      (tryptic soy agar plus 0.6% yeast extract) and L. monocytogenes (PALCAM agar)
      populations were determined on day 0 and at the endpoint of storage. The
      combinations of parameters that allowed increases in cell counts of L.
      monocytogenes of at least l log CFU/cm2 were assigned the value of 1, while those
      limiting growth to <1 log CFU/cm2 were given the value of 0. The binary data were
      used in logistic regression analysis for development of models to predict
      boundaries between growth and no growth of the pathogen at desired probabilities.
      Indices of model performance and validation with limited available data indicated
      that the models developed had acceptable goodness of fit. Thus, the described
      procedures using bacterial growth data from studies with food products may be
      appropriate in developing growth/no growth models to predict growth and to select
      lactic acid concentrations and dipping times for control of L. monocytogenes.
      PRACTICAL APPLICATION: The models developed in this study may be useful in
      selecting lactic acid concentrations and dipping times to control growth of
      Listeria monocytogenes on cured ham and uncured turkey breast during product
      storage, and in determining probabilities of growth under selected conditions.
      The modeling procedures followed may also be used for application in model
      development for other products, conditions, or pathogens.

PMID- 22417517
TI  - Antimicrobial activity of Yerba Mate (Ilex paraguariensis) aqueous extracts
      against Escherichia coli O157:H7 and Staphylococcus aureus.
AB  - Bioactive compounds from natural plant sources are becoming increasingly
      important to the food industry. Ilex paraguariensis is used in the preparation of
      a widely popular tea beverage (Yerba Mate) in the countries of Uruguay, Paraguay,
      Argentina, and Brazil. In this study, extracts of 4 brands of commercial tea,
      derived from the holly plant species, Ilex paraguariensis, were evaluated for
      their ability to inhibit or inactivate bacterial foodborne pathogens. The
      ultimate goal was to evaluate potential use of the extracts in commercial
      applications. Dialyzed aqueous extracts were screened for antimicrobial activity
      against Escherichia coli O157:H7 and Staphylococcus aureus. S. aureus was found
      to be the more sensitive to extracts than E. coli O157:H7. Minimum bactericidal
      concentrations (MBCs) were determined to be approximately 150 to 800 MUg/mL and
      25 to 50 MUg/mL against E. coli O157:H7 and S. aureus, respectively. A Uruguayan
      brand had reduced activity against E. coli O157:H7 compared to the Argentinean
      brands tested. It was concluded that Yerba Mate could be used as a potential
      antimicrobial in foods and beverages against these pathogenic bacteria. PRACTICAL
      APPLICATION: Soluble extracts from Yerba Mate are natural antimicrobials that can
      be incorporated into food products to achieve longer shelf life.

PMID- 22417519
TI  - Quality assessment of filtered smoked yellowfin tuna (Thunnus albacares) steaks.
AB  - Filtered smoke (FS) has been used to preserve taste, texture, and/or color in
      tuna and other fish species. This treatment is particularly important in color
      preservation during frozen storage. The objective of this study was to compare
      changes in the quality profiles of FS-treated and untreated (UT) yellowfin tuna
      (Thunnus albacares) steaks stored in 3 ways: room temperature (21 to 22  degrees
      C), refrigerated (4 to 5  degrees C), and iced (0  degrees C). FS and UT steaks
      were processed from the same lot of fish and analyzed for chemical,
      microbiological, lipid oxidation, color, and sensory profiles. Similar trends
      were seen for microbial proliferation and accumulation of apparent ammonia and
      total volatile base nitrogen (TVB-N) during the storage temperatures evaluated.
      Notable exception in quality profile was found in lipid oxidation which was, as
      expected, lower for treated samples at all storage temperatures for TBARS (P <
      0.05) and lower or significantly (P < 0.05) lower for POV values. FS increased
      the initial redness value significantly (P < 0.05). Unlike UT product, there was
      no loss of color value concomitant with quality changes for FS-treated tuna for
      all storage temperatures evaluated. PRACTICAL APPLICATION: The overall goal of
      this project was to evaluate filtered smoked tuna steaks as to the impact on the
      overall quality profile. As a color-stabilizing technology, it could mask
      deteriorating quality.

PMID- 22417518
TI  - A brief review of the occurrence, use, and safety of food-related nanomaterials.
AB  - Nanotechnology and nanomaterials have tremendous potential to enhance the food
      supply through novel applications, including nutrient and bioactive absorption
      and delivery systems; ingredient functionality; improved colors and flavors;
      microbial, allergen, and contaminant detection and control; and food packaging
      properties and performance. To determine the current state of knowledge regarding
      the safety of these potential uses of nanomaterials, an appraisal of the
      published literature on the safety of food-related nanomaterials was undertaken.
      A method of assessment of reliability of toxicology studies was developed to
      conduct this appraisal. The review of the toxicology literature on oral exposure
      to food-related nanomaterials found that the number of studies is limited.
      Exposure to nanomaterials in the human food chain may occur not only through
      intentional uses in food manufacturing, but also via uses in agricultural
      production and carry over from use in other industries. Although a number of
      analytical methods are useful in physicochemical characterization of manufactured
      nanomaterials, new methods may be needed to more fully detect and characterize
      nanomaterials incorporated into foods and in other media. There is a need for
      additional toxicology studies of sufficient quality and duration on different
      types of nanomaterials to further our understanding of the characteristics of
      nanomaterials that affect safety of oral exposure resulting from use in various
      food applications.

PMID- 22417520
TI  - Staling of cereal bran enriched cakes and the effect of an endoxylanase enzyme on
      the physicochemical and sensorial characteristics.
AB  - The staling of cakes enriched with untreated brans and endoxylanase-treated brans
      was evaluated by monitoring the changes in physicochemical, thermal, and
      sensorial properties of cakes during 7-d storage. Oat and rice bran were treated
      with different levels (0, 70, and 700 ppm) of an endoxylanase enzyme and added to
      cakes on 30% flour weight basis. Moisture losses, water activity, crumb firmness,
      starch retrogradation, and sensorial characteristics were used as staling
      indicators. Avrami-type equations were efficiently used for modeling the starch
      retrogradation kinetics, while linear models most adequately described crumb
      firming kinetics. Cake staling induced an increase in crumb firmness and enthalpy
      of amylopectin retrogradation, and a decrease in crumb moisture and sensory
      quality and acceptability scores of cakes. Oat bran-containing cakes better
      maintained their characteristics compared to the ones containing rice bran along
      the 7-d storage. Endoxylanase treatment of brans delayed the changes naturally
      induced during staling in crumb moisture content, amylopectin retrogradation
      enthalpy, and crumb firmness in the respective cakes. Deterioration of the
      sensorial characteristics was slower for the cakes containing endoxylanase
      treated brans, as well. The level of endoxylanase treatment did not differentiate
      significantly (P < 0.05) any of the staling indicators. Overall, this study
      demonstrated that addition of endoxylanase-treated brans can result in cakes with
      improved nutritional characteristics and increased shelf life. PRACTICAL
      APPLICATION: The results of the study show the potential of using enzymes to
      modify underutilized food sources that can be properly incorporated in baked
      goods, improving their nutritional value, their quality characteristics, and
      providing longer shelf life. The developed procedure and results can be utilized
      by the bakery industry to make high fiber and low cost bakery products with
      improved sensorial characteristics that are appealing to the consumers.

PMID- 22417521
TI  - Characteristics of formed Atlantic salmon jerky.
AB  - Smoked salmon (Salmo salar L.) processing may generate large amounts of small
      pieces of trimmed flesh that has little economic value. Opportunities exist to
      develop new added-value foods from this by-product. Brining was compared with dry
      salting for the production of formed salmon jerky-style strips that were then
      smoked. The formulations also contained brown sugar and potato starch. Salted
      samples had higher salt concentrations and required less force to break using a
      TA-XT2 Texture Analyzer. Brined samples contained more fat and were darker,
      redder and more yellow than the salted samples. Processing concentrated omega-3
      fatty acids compared with raw salmon, and the brined jerky had the highest omega
      3 fatty acid content. A panel of 57 consumers liked the appearance and aroma of
      both samples equally (approximately 6.7 for appearance and 6.3 for aroma on the 9
      point hedonic scale. Higher acceptability scores for taste, texture, and overall
      quality were given to the brined product (6.7 to 6.9 against 6.2 to 6.3).
      PRACTICAL APPLICATION: Salmon trim from smoking facilities can be utilized to
      produce a jerky that is a good source of omega-3 fatty acids, simultaneously
      adding value and reducing the waste stream.

PMID- 22417522
TI  - Identification of tartary buckwheat tea aroma compounds with gas chromatography
      mass spectrometry.
AB  - Tartary buckwheat tea, which is an important and healthy product, has a distinct
      malty aroma. However, its characteristic aroma compounds have not been
      elucidated. The aims of present study were identification and quantification of
      its aroma compounds. The analyses were performed by gas chromatography-mass
      spectrometry (GC-MS) after 3 different isolation techniques. Seventy-seven
      compounds were identified. Among these compounds, 35 were quantified by available
      standards. The compounds with a high probability of contribution to the tartary
      buckwheat tea aroma (OAV >= 10) were as follows: 2,5-dimethyl-4-hydroxy-3(2H)
      furanone, nonanal, 2,3-diethyl-5-methylpyrazine, benzeneacetaldehyde, maltol, 2,5
      dimethylpyrazine, 2-ethyl-5-methylpyrazine, trimethylpyrazine. Some nutritional
      and bioactive compounds were also identified in this study, such as linoleic
      acid, niacin, vanillic acid, 7-hydroxycoumarin, butylated hydroxytoluene.
      Practical Application: Tartary buckwheat, one type of buckwheat, has gained much
      attention from nutritionists and medical doctors in recent years. It is rich in
      rutin, quercetin, and other nutrients that are good for health. Tartary buckwheat
      based product such as tartary buckwheat tea is an important and popular healthy
      product in China, Japan,South Korea, European countries as well as in American
      countries. It has a distinct malty aroma. The present study first identified and
      quantified of its aroma compounds. The results will draw attention to other
      researchers in food flavor and buckwheat filed.

PMID- 22417523
TI  - Effect of food azo dye tartrazine on learning and memory functions in mice and
      rats, and the possible mechanisms involved.
AB  - Tartrazine is an artificial azo dye commonly used in human food and
      pharmaceutical products. The present study was conducted to evaluate the toxic
      effect of tartrazine on the learning and memory functions in mice and rats.
      Animals were administered different doses of tartrazine for a period of 30 d and
      were evaluated by open-field test, step-through test, and Morris water maze test,
      respectively. Furthermore, the biomarkers of the oxidative stress and
      pathohistology were also measured to explore the possible mechanisms involved.
      The results indicated that tartrazine extract significantly enhanced active
      behavioral response to the open field, increased the escape latency in Morris
      water maze test and decreased the retention latency in step-through tests. The
      decline in the activities of catalase, glutathione peroxidase (GSH-Px), and
      superoxide dismutase (SOD) as well as a rise in the level of malonaldehyde (MDA)
      were observed in the brain of tartrazine-treated rats, and these changes were
      associated with the brain from oxidative damage. The dose levels of tartrazine in
      the present study produced a few adverse effects in learning and memory functions
      in animals. The mechanisms might be attributed to promoting lipid peroxidation
      products and reactive oxygen species, inhibiting endogenous antioxidant defense
      enzymes and the brain tissue damage. PRACTICAL APPLICATION: Tartrazine is an
      artificial azo dye commonly used in human food and pharmaceutical products. Since
      the last assessment carried out by the Joint FAO/WHO Expert Committee on Food
      Additives in 1964, many new studies have been conducted. However, there is a
      little information about the effects on learning and memory performance. The
      present study was conducted to evaluate the toxic effect of tartrazine on the
      learning and memory functions in animals and its possible mechanism involved.
      Based on our results, we believe that more extensive assessment of food additives
      in current use is warranted.

PMID- 22417524
TI  - Sea buckthorn (Hippophae rhamnoides) proanthocyanidins inhibit in vitro enzymatic
      hydrolysis of protein.
AB  - Interactions of phenolics with other food constituents and digestive enzymes are
      likely to have interference with the digestion and bioavailability of food and
      phenolics. In this study the effect of sea buckthorn proanthocyanidins on in
      vitro digestion of protein was evaluated. Optimization of the extraction
      conditions showed that maximum recovery of sea buckthorn proanthocyanidins was
      obtained with acidified acetone; water mixture (60% to 70%, v/v). Crude
      proanthocyanidin extracts thus prepared were purified using sephadex gel column
      chromatography and their average degree of polymerization and the effects on
      enzymatic hydrolysis of bovine serum albumin as influenced by their protein
      precipitation capacities were studied. Average degree of polymerization of
      proanthocyanidins in berry pulp, kernel, seed coat, and leaves was 7.4, 5.6, 8.2,
      and 10.6, respectively. The EC50 values for the protein precipitation by the PA
      of berry pulp, kernel seed coat, and leaves were 44.2, 44.1, 65.8, and 39.8 MUg,
      respectively. Relative enzymatic hydrolysis of the protein-proanthocyanidin
      complexes was 44.1% to 60.3% for pepsin and 57.5% to 67.7% for trypsin.
      Interactions of sea buckthorn proanthocyanidins with food proteins and digestive
      enzymes might alter the protein digestibility and phenolic bioavailabilty.

PMID- 22417525
TI  - Development of a lateral flow immunoassay (LFA) strip for the rapid detection of
      1-aminohydantoin in meat samples.
AB  - Due to the potential toxic effects of the nitrofuran family of antibiotics, their
      use in animals in the food industry has raised health concerns. This study was
      aimed to develop a lateral flow assay (LFA) based on competitive format for the
      detection of 1-aminohydantoin (AHD) in meat samples. The assay could be completed
      in 1 min and detected AHDs derivates (CPAHD) at 3 ng/mL, equivalent to 1.40 ng/mL
      of AHD, which was much lower than that reported in the literature by similar
      method. The antibody showed no cross-reactivity with a panel of more than 10
      nitrofuran analogs except for nitrofurantoin at a high concentration. The test
      strip was stable at room temperature for up to 8 wk or at 37  degrees C for 4 wk.
      Parallel analyses of meat samples with LFA and enzyme-linked immunosorbent assay
      (ELISA) obtained data in good agreement. This developed gold nanoparticle based
      LFA had a good specificity, sensitivity, stability, and reliability. It was
      potentially suitable for on-the-spot large-scale screening of meat samples, and
      even more other applications. PRACTICAL APPLICATION: Nitrofurantoin is one of
      antibiotics of the nitrofuran family, which has been used not only to prevent and
      treat diseases, but also to promote growth in animals. However, concerning the
      carcinogenicity of the metabolite of nitrofurantoin (AHD), a new fast and
      convenient method for monitoring AHD should be established. We describe the
      development of a new test assay for rapid screening of meat samples.

PMID- 22417526
TI  - Free radical scavenging, cytotoxic, and hemolytic activities of an active
      antioxidant compound ethyl gallate from leaves of Acacia nilotica (L.) Wild. Ex.
      Delile subsp. indica (Benth.) Brenan.
AB  - In the present study, free radical scavenging, cytotoxic, and hemolytic
      activities of the polyphenolic compound ethyl gallate isolated from ethanol
      extract of Acacia nilotica Wild. Ex. Del. leaves were determined. The free
      radical-scavenging activities of the ethyl gallate were demonstrated in several
      in vitro assays in order to evaluate the possible antioxidant mechanism. The
      results revealed ethyl gallate as hydrogen donor, metal chelator, and free
      radical scavenger. Ethyl gallate was effective in scavenging 1,1-Diphenyl-2
      picrylhydrazyl (DPPH) radicals and the IC50 value was lower than all the positive
      controls used in this study. Deoxyribose degradation assay revealed that ethyl
      gallate had more iron-chelating ability than the direct hydroxyl radical
      scavenging ability. The results of the cytotoxic study revealed that the compound
      was moderately active and IC50 value was found to be >100 MUg/mL for Vero cell
      lines and 72 MUg/mL for Hela cell lines. The compound possessed no hemolytic
      activity against rat and human erythrocytes revealing its cytotoxic mechanism and
      nontoxicity. The results from this work will provide an important information for
      the food and pharmacological industries with respect to the use of the compound
      as an antioxidant and a health-related drug. PRACTICAL APPLICATION: Antioxidant
      from plant sources is safe to use, as compared to synthetic products. It also can
      be used as a supplement to alleviate most of the diseases because of its free
      radical-scavenging activity.

PMID- 22417527
TI  - Reduction of fumonisin B1 in corn grits by twin-screw extrusion.
AB  - This study was designed to investigate the fate of fumonisins in flaking corn
      grits during twin-screw extrusion by measuring fumonisin B1 (FB1) and its analogs
      with a mass balance approach. Food grade corn grits and 2 batches of grits
      contaminated with FB1 at 10 and 50 MUg/g by Fusarium verticillioides M-2552 were
      processed with or without glucose supplementation (10%, w/w) with a twin-screw
      extruder. Extrusion reduced FB1 in contaminated grits by 64% to 72% without
      glucose and 89% to 94% with added glucose. In addition, extrusion alone resulted
      in 26% to 73% reduction in the levels of fumonisin B2 and fumonisin B3, while
      levels of both mycotoxins were reduced by >89% in extruded corn grits containing
      10% glucose. Mass balance analysis showed that 38% to 46% of the FB1 species
      detected in corn extruded with glucose was N-(deoxy-D-fructos-1-yl)-FB1, while
      23% to 37% of FB1 species detected in extruded corn grits with and without added
      glucose was bound to the matrix. It was also found that the hydrolyzed form of
      FB1 was a minor species in extruded corn grits with or without added glucose,
      representing <15% of the total FB1 species present. Less than 46% of FB1
      originally present in corn grits could be detected in the fumonisin analogues
      measured in this study. Research is needed to identify the reaction products
      resulting from extrusion processing of fumonisin-contaminated corn products.
      PRACTICAL APPLICATION: Twin-screw extrusion is widely used in food industry for
      its versatility. This technology may reduce the level of fumonisins in corn
      particularly with added glucose.

PMID- 22417531
TI  - The critical illness polyneuropathy in septic patients with prolonged weaning
      from mechanical ventilation: is the diaphragm also affected? A pilot study.
AB  - BACKGROUND: Critical illness myopathy and/or neuropathy (CRIMYNE) is a common
      alteration seen in the ICU. The currently available bedside methods of measuring
      respiratory and peripheral muscle function in critically ill patients are
      somewhat inadequate. The objective of this study was  to evaluate the presence of
      diaphragmatic and peripheral CRIMYNE in septic patients with prolonged weaning
      from mechanical ventilation (MV). METHODS: Cohort prospective study with an entry
      period of 6 months. In 2 Brazilian medical-surgical ICUs, septic patients >= 18
      years of age, dependent  on MV >= 14 days, requiring prolonged weaning from MV,
      awake (Richmond Agitation Sedation Scale >= -2), and with no previous history of
      polyneuropathy or myopathy were included. Electrophysiological studies of the
      limbs and also of the respiratory system by phrenic nerve conduction  and needle
      electromyography of the diaphragm were performed in all subjects. RESULTS: Twelve
      subjects were enrolled during 6 months of study. The electrophysiological signs
      of peripheral CRIMYNE occurred in 9 subjects, 7 of whom died in the ICU. Three
      subjects developed critical illness polyneuropathy,  4 critical illness myopathy,
      and 2 both. Only one subject who developed peripheral CRIMYNE did not present
      diaphragmatic involvement, whereas no subject developed diaphragm involvement
      alone. Thus, electrophysiological signs of diaphragmatic CRIMYNE occurred in 8 of
      the 9 subjects with peripheral  CRIMYNE. Upon clinical examination, 8 subjects
      were not able to moves their limbs against gravity, and these findings were
      related to the presence of peripheral and diaphragmatic dysfunction. CONCLUSIONS:
      Our pilot findings suggested that CRIMYNE is common in septic patients with
      prolonged  weaning from MV (MV >= 14 d). The inability to move limbs against
      gravity is frequently associated with peripheral and diaphragmatic CRIMYNE, and
      the findings of CRIMYNE in peripheral electrophysiological tests are associated
      with diaphragmatic involvement.

PMID- 22417532
TI  - Development and application of a delayed-release anthelmintic intra-ruminal bolus
      system for experimental manipulation of nematode worm burdens.
AB  - In order to quantify the impact of parasites on host population dynamics,
      experimental manipulations that perturb the parasite-host relationship are needed
      but, logistically, this is difficult for wild hosts. Here, we describe the use of
      a delayed-release anthelmintic delivery system that can be administered when the
      hosts can be captured and its activity delayed until a more appropriate period in
      the host-parasite cycle. Our model system is Svalbard reindeer infected with a
      nematode parasite, Marshallagia marshalli, which appears to accumulate during the
      Arctic winter. To determine the extent to which this occurs and the effect on
      host fitness, reindeer need to be treated with anthelmintics in late autumn but
      they can only be caught and handled in April. To solve this problem, we devised
      an intra-ruminal capsule that releases the anthelmintic from up to 6 months after
      being administered. The capsule was trialed in cannulated sheep and red deer to
      determine optimum capsule orifice size and release rates. Capsules were estimated
      to release placebo for 100-153 days followed by abamectin for 22-34 days. To test
      the efficacy of treatment in reindeer, capsules were administered in April and
      retrieved in October. All capsules had fully released the anthelmintic and
      treated reindeer had significantly lower worm burdens than controls. Thus,
      success of this system allows repeated treatment over several years to test the
      effect of winter parasitism on host fitness.

PMID- 22417533
TI  - MacA is a second cytochrome c peroxidase of Geobacter sulfurreducens.
AB  - The metal-reducing delta-proteobacterium Geobacter sulfurreducens produces a
      large number of c-type cytochromes, many of which have been implicated in the
      transfer of electrons to insoluble metal oxides. Among these, the dihemic MacA
      was assigned a central role. Here we have produced G. sulfurreducens MacA by
      recombinant expression in Escherichia coli and have solved its three-dimensional
      structure in three different oxidation states. Sequence comparisons group MacA
      into the family of diheme cytochrome c peroxidases, and the protein indeed showed
      hydrogen peroxide reductase activity with ABTS(-2) as an electron donor. The
      observed K(M) was 38.5 +/- 3.7 MUM H(2)O(2) and v(max) was 0.78 +/- 0.03 MUmol of
      H(2)O(2).min(-1).mg(-1), resulting in a turnover number k(cat) = 0.46 . s(-1). In
      contrast, no Fe(III) reductase activity was observed. MacA was found to display
      electrochemical properties similar to other bacterial diheme peroxidases, in
      addition to the ability to electrochemically mediate electron transfer to the
      soluble cytochrome PpcA. Differences in activity between CcpA and MacA can be
      rationalized with structural variations in one of the three loop regions, loop 2,
      that undergoes conformational changes during reductive activation of the enzyme.
      This loop is adjacent to the active site heme and forms an open loop structure
      rather than a more rigid helix as in CcpA. For the activation of the protein, the
      loop has to displace the distal ligand to the active site heme, H93, in loop 1. A
      H93G variant showed an unexpected formation of a helix in loop 2 and disorder in
      loop 1, while a M297H variant that altered the properties of the electron
      transfer heme abolished reductive activation.

PMID- 22417534
TI  - Cellular damage and apoptosis along with changes in NF-kappa B expression were
      induced with contrast agent enhanced ultrasound in gastric cancer cells and
      hepatoma cells.
AB  - BACKGROUND: The effect of cell injury and apoptosis induced by ultrasound with
      contrast agent has been verified. Contrast agent enhanced apoptosis and
      expression of genes that related to apoptosis and are responsive to ultrasound.
      This effect was associated with reactive oxygen species (ROS) production induced
      by the sonochemical reaction, as reported in previous studies. NF-kappa B may be
      one of the factors involved in oxidizing reactions or modulation during the
      process of ultrasound inducing apoptosis. RESULTS: Ultrasound irradiated gastric
      cancer cells (SGC7901 cell line) and hepatocellular carcinoma cells (SMMC-771
      cell line) cultured in medium containing contrast agent. Significant cellular
      damage and apoptosis were observed in the bath cells incubated for 24 hours
      following 120 seconds ultrasonic irradiation. I kappa B alfa expression
      synchronously increased in the treatment groups of both the cell lines, and the
      down-regulated expression of NF-kappa B influenced its-regulated expression of
      genes that related to apoptosis. Production of intracellular ROS and elevation of
      NF-kappa B level occurred after incubation of the cells for 1 hour following
      ultrasonic treatment. CONCLUSIONS: Our result suggested that contrast agent
      enhanced the biological effect of ultrasound. Their reaction might stimulate the
      transitory expression of NF-kappaB, and subsequent elevation in IkappaBalfa
      expression could lead to the apoptosis of SGC7901 cells and SMMC-771 cells.

PMID- 22417535
TI  - Proposed DSM-5 mixed features are associated with greater likelihood of remission
      in out-patients with major depressive disorder.
AB  - BACKGROUND: Draft DSM-5 criteria for a mixed major depressive episode have been
      proposed, but their predictive validity has not yet been established. We
      hypothesized that such symptoms would be associated with poorer antidepressant
      treatment outcomes. METHOD: We examined outcomes among individuals with major
      depressive disorder participating in the Sequenced Treatment Alternatives to
      Relieve Depression (STAR*D) study, an effectiveness study conducted at primary
      and specialty care centers in the USA. Mixed features were derived from the six
      self-report items of the mania subscale of the Psychiatric Diagnosis Screening
      Questionnaire. Primary analyses examined the association between the presence of
      at least two of these in the 6 months before study entry, and remission across up
      to four sequential treatment trials, as well as adverse outcomes. RESULTS: Of the
      2397 subjects with a major depressive episode of at least 6 months' duration, 449
      (18.7%) reported at least two mixed symptoms. The presence of such symptoms was
      associated with a greater likelihood of remission across up to four sequential
      treatments, which persisted after adjustment for potential confounding clinical
      and demographic variables (adjusted hazard ratio 1.16, 95% confidence interval
      1.03-1.28). Two individual items, expansive mood and cheerfulness, were strongly
      associated with a greater likelihood of remission. CONCLUSIONS: Proposed DSM-5
      mixed state features were associated with a greater rather than a lesser
      likelihood of remission. While unexpected, this result suggests the potential
      utility of further investigation of depressive mixed states in major depression.

PMID- 22417536
TI  - Interactions between hemoglobin and cod muscle constituents following treatment
      at extreme pH values.
AB  - Acid and/or alkaline solubilization is a recent method developed to separate
      proteins from muscle foods with good functional properties. However, exposure of
      the muscle and its components to low pH values has been shown to promote lipid
      oxidation, limiting therefore the applications of this novel method. This
      research aimed primarily to study the physicochemical changes of the fish
      membranes brought about during acid or alkali solubilization processes. The
      effect on lipid oxidation and the possible role of the water soluble fraction of
      the muscle (press juice) as a potent antioxidant were also investigated. Model
      systems comprising minced cod muscle or cod microsomal suspensions were used.
      Results showed that acid or alkaline treatment (pH < 3.5 or pH > 10.5) of cod
      membranes significantly delayed lipid oxidation. Added triacylglycerols to washed
      cod system treated at low pH did not enhance hemoglobin-mediated lipid oxidation.
      Decreased precipitation of hemoglobin was observed with the alkali-treated
      membranes at all protein concentrations compared to the acid-treated and the
      untreated membranes. Finally, the addition of press juice to washed cod muscle
      tissue or to the membrane model system, significantly delayed hemoglobin lipid
      oxidation. PRACTICAL APPLICATION: The results of this study can be used to
      improve pH-shifting technologies to avoid or decrease lipid oxidation problems.
      Also, the use of press-juice from cod muscle as means of protecting the muscle
      against lipid oxidation is suggested.

PMID- 22417537
TI  - Selective removal of the violet color produced by anthocyanins in procyanidin
      rich unfermented cocoa extracts.
AB  - Cacao (Theobroma cacao L.) is rich in procyanidins, a large portion of which
      degrades during the natural fermentation process of producing cocoa powder.
      Recent advances in technology have enabled scientists to produce unfermented
      cocoa powder, preserving the original profile of procyanidins present in cocoa
      and allowing for the development of highly concentrated procyanidin-rich
      extracts. During this process, the anthocyanins naturally present in unfermented
      cocoa remain intact, producing a violet color in the final extract. The objective
      of this study was to selectively remove the violet color in procyanidin-rich
      extracts produced from unfermented cocoa powder, while maintaining the stability
      and composition of procyanidins present in the matrix. Several processing
      parameters, including pH fluctuations, enzymatic treatments, and the addition of
      potassium meta-bisulfite, were explored to influence the color of procyanidin
      rich extracts throughout a 60-d shelf life study. The addition of potassium meta
      bisulfite (500 ppm) was found to be the most effective means of removing the
      violet color present in the treated extracts (L*= 71.39, a*= 8.44, b*= 9.61,
      chroma = 12.79, and hue = 48.8) as compared to the control (L*= 52.84, a*= 11.08,
      b*= 2.24, chroma = 11.28, and hue = 11.4). The use of potassium meta-bisulfite at
      all treatment levels (200, 500, and 1000 ppm) did not show any significant
      detrimental effects on the stability, composition, or amount of procyanidins
      present in the extracts over the shelf life period as monitored by UV-Vis
      spectrophotometry and HPLC-MS. This research will enable the food industry to
      incorporate highly concentrated procyanidin-rich extracts in food products
      without influencing the color of the final product.

PMID- 22417538
TI  - Thermal denaturation of tilapia myosin and its subunits as affected by constantly
      increasing temperature.
AB  - Purified tilapia myosin was digested with alpha-chymotrypsin and purified to
      obtain heavy meromyosin (HMM) and light meromyosin (LMM). Biochemical properties
      of tilapia myosin, HMM, and LMM were characterized. Surface hydrophobicity (S(o)
      ) showed an increase for myosin and HMM between 30 and 40  degrees C and reached
      a plateau at 70  degrees C. LMM, in a small magnitude, also showed a continuous
      increase to 70  degrees C. Total sulfhydryl content (TSH) demonstrated that the
      SH residue content of HMM was nearly double that of LMM. Surface reactive
      sulfhydryl groups (SRSH) for myosin and HMM were relatively unchanged from 10 to
      30  degrees C but increased from 30 to 50  degrees C. The exposure of buried
      hydrophobic and sulfhydryl groups of myosin and HMM increased as the myosin and
      HMM were constantly heated. However, the TSH and SRSH results indicated that the
      stability of LMM was likely due to its alpha-helix conformation. Reducing and
      nonreducing sodium dodecylsulfate-polyacryamide gel electrophoresis helped to
      understand the role of disulfide bonds in thermal aggregation of tilapia myosin,
      HMM, and LMM.

PMID- 22417539
TI  - Partial replacement of pork back-fat by vegetable oils in burger patties: effect
      on oxidative stability and texture and color changes during cooking and chilled
      storage.
AB  - The present study was aimed to examine the impact of partial back-fat replacement
      (50%) by avocado (A), sunflower (S), and olive (O) oil on the chemical
      composition, oxidative stability, color, and texture of porcine burger patties
      (10% fat) subjected to oven cooking (170  degrees C/18 min) and chilling (+ 4 
      degrees C/15 d). The addition of vegetable oils caused a significant reduction of
      saturated fatty acids and a concomitant enrichment in unsaturated fatty acids.
      The incorporation of vegetable oils to porcine patties caused a significant
      reduction of TBARS formed as a result of cooking and the subsequent chilling. The
      usage of vegetable oils as back-fat replacers had no impact on the formation of
      protein carbonyls. Porcine patties with A- and O-patties displayed a more
      favorable ratio between volatiles contributing to rancidity and those
      contributing pleasant odor notes. Treated and control patties underwent similar
      discoloration during processing. The usage of vegetable oils and particularly,
      avocado and olive oils, as back-fat replacers, could be an interesting strategy
      to improve the nutritional and technological properties of porcine patties.
      PRACTICAL APPLICATION: The present study highlights the potential nutritional and
      technological benefits of replacing animal fat by vegetable oils in porcine
      patties subjected to cooking and chilling. The industrial application of
      vegetable oils in processed meat products would meet the current consumers'
      interest towards healthier food products. In addition, the usage of avocado oil
      would contribute to boost the avocado industry by providing an additional value
      to a by-product of great biological significance.

PMID- 22417540
TI  - Volatile compounds and sensory analysis of both harvests of double-cut Yakima
      peppermint (Mentha piperita L.).
AB  - North American peppermint oils are widely regarded as some of the most superior
      peppermint oils commercially available. Amongst them is Yakima double-cut
      peppermint oil (Mentha piperita L.). It has an aroma described as strong,
      refreshing, minty, slightly creamy, and very herbaceous with some of the most
      desirable flavor notes among peppermint oils. The peppermint is grown in the
      Yakima Valley of Washington State, USA. As one of the most northerly grown
      peppermints with longer days, it is unique as there are 2 harvests of the mint
      leaves in one season. For this study, samples of fresh and dried (hay) leaves
      were collected from both harvests; 1st cut, July and 2nd cut, September. Steam
      distilled oils were produced from each harvest and analyzed by gas chromatography
      mass spectrometry to give detailed profiles. The aroma and taste sensory
      attributes of each oil were evaluated. In addition, menthyl formate has
      previously been reported only once in the literature, but not as definitively as
      required by current flavor-regulatory bodies for use as a natural flavoring
      ingredient. It was conclusively reported in these peppermint oils.

PMID- 22417541
TI  - Kinetics of 3-deoxy-D-erythro-hexos-2-ulose in unifloral honeys.
AB  - In this study, for the first time, the amount of 3-deoxy-D-erythro-hexos-2-ulose
      (3-DG) in fresh citrus and chestnut honeys was determined. 3-DG was measured as
      the corresponding quinoxalines after derivatization with orthophenylenediamine
      using reverse-phase high-performance liquid chromatography (RP-HPLC).
      Notwithstanding the freshness of the samples, high levels of 3-DG were detected
      in both honeys. The comparison of 3-DG and 5-hydroxymethylfurfural (HMF)
      concentrations, which was also quantified by RP-HPLC, showed that citrus honeys
      had the lowest amount of 3-DG (107 mg/kg) and the highest of HMF (16.7 mg/kg),
      while chestnut honeys had the opposite (398 and 1.2 mg/kg, respectively). During
      thermal treatment, different 3-DG and HMF trends were highlighted between the
      citrus and chestnut honeys; at the end, 3-DG formation was more favored with
      respect to HMF formation. Moreover, in citrus honeys, a good correlation between
      3-DG and HMF levels was observed, which was not found in chestnut honeys,
      suggesting a role of the high pH values of these honeys on the degradation
      routes. The kinetic analysis showed the highest k value for 3-DG and HMF
      formation in chestnut and citrus honeys, respectively. The lowest Ea values
      related to 3-DG formation and the highest to HMF formation, indicating that the
      key intermediate 3-DG is easily formed at low temperatures, whilst the formation
      of HMF requires higher temperatures. For this reason, 3-DG seems to be an aging
      index rather than a thermal index and its use, at least for honeys at high pH
      values, together with HMF, could improve their quality assessment.

PMID- 22417542
TI  - Thermophysical characterization of tilapia myosin and its subfragments.
AB  - Purified tilapia myosin was digested with alpha-chymotrypsin and purified to
      obtain heavy meromyosin (HMM) and light meromyosin (LMM). The thermophysical
      properties of Tilapia myosin, HMM, and LMM were characterized. Constantly heated
      myosin, HMM, and LMM samples showed that aggregates began to form around 40 
      degrees C as evidenced by the increase of turbidity for all 3 samples (0.25
      mg/mL). Beginning turbidity measurements showed differing levels of absorbance
      for each protein fragment with increasing absorbance values in the following
      order HMM, myosin, and LMM (0.0026, 0.0282, and 0.052, respectively).
      Differential scanning calorimetry showed 3 (17.5, 41.9, and 49.9  degrees C), 2
      (43 and 67.1  degrees C), and 3 (40.4, 51.7, and 69  degrees C) major peaks for
      myosin, HMM, and LMM, respectively. Dynamic rheology measurements demonstrated
      crossover points, which are generally recognized as gelation point, 40.3  degrees
      C for myosin and 27  degrees C for HMM. The results shown for the thermally
      stable properties of tilapia myosin, HMM, and LMM showed clear evidence that they
      are all thermal stable at temperatures ranging from 10  degrees C to
      approximately 40  degrees C after which they all are completely denatured. The
      results also showed that the thermo stability of the myosin and its subfragments
      were greatly influenced by fish habitat temperature.

PMID- 22417543
TI  - Effect of gamma-irradiation on bioactivity, fatty acid compositions and volatile
      compounds of clary sage seed (Salvia sclarea L.).
AB  - Clary sage seeds (Salvia sclarea L.) were obtained from plants cultivated, and
      2.5, 4.0, 5.5, and 7.0 kGy doses of gamma-irradiation were applied to the clary
      sage seeds. They were then analyzed for their protein, ash, oil and dry matter
      contents, and fatty acid composition. Additionally, the total phenolic contents,
      antiradical, antioxidant activities, and volatile compounds of the clary sage
      seed extract were determined. There was no significant difference in protein
      content. However, the moisture, oil, and ash contents of the samples were
      affected by irradiation. While the 7 kGy dose had a positive effect on the total
      phenolic content and antiradical activity of the sage seed extract, all doses
      have negative effects on the antioxidant activity of the sage seed. The main
      fatty acid of the sage seed was remarkably found as alpha-linolenic acid. The
      four irradiation levels caused significant differences in fatty acid composition
      by affecting all fatty acids except palmitic, palmitoleic, and eicosenoic acids.
      The dominant volatile compounds of control sage seed were found as beta-pinene
      (18.81%) and limonene (15.60%). Higher doses of the irradiation decreased
      volatile components of sage seed. Clary sage seed including high omega-3 can be
      irradiated with low doses (<= 2.5 kGy) of gamma-irradiation. PRACTICAL
      APPLICATION: Clary sage is one of the most popular Salvia species in Turkey and
      many countries. Clary sage seed has approximately 29% oil content and this oil
      contains >50% of alpha-linolenic acid. gamma-Irradiation is widely applied in the
      preservation of spice quality. The present study shows that the antioxidant
      activity of the clary sage seed is decreased by gamma-irradiation. Additionally,
      higher doses of irradiation also decreased the volatile components of sage seed.
      Therefore, we suggest that clary sage seed which includes high levels of omega-3
      should be irradiated with low doses (<= 2.5 kGy) of gamma-irradiation.

PMID- 22417544
TI  - Effects of anticaking agents and relative humidity on the physical and chemical
      stability of powdered vitamin C.
AB  - Vitamin C is an essential nutrient that is widely used by the food industry in
      the powder form for both its nutritional and functional properties. However,
      vitamin C is deliquescent, and deliquescence has been linked to physical and
      chemical instabilities. Anticaking agents are often added to powder systems to
      delay or prevent caking, but little is known about their effect on the chemical
      stability of powders. In this study, various anticaking agents (calcium
      phosphate, calcium silicate, calcium stearate, corn starch, and silicon dioxide)
      were combined with sodium ascorbate at 2% and 50% w/w ratios and stored at
      various relative humidities (23%, 43%, 64%, 75%, 85%, and 98% RHs). Chemical and
      physical stability and moisture sorption were monitored over time. Additionally,
      saturated solution samples were stored at various pHs to determine the effect of
      surface pH and dissolution on the vitamin degradation rate. Storage RH, time, and
      anticaking agent type and ratio all significantly affected (P < 0.05) moisture
      sorption and vitamin C stability. Silicon dioxide and calcium silicate (50% w/w)
      and calcium stearate (at both ratios) were the only anticaking agents to improve
      the physical stability of powdered sodium ascorbate while none of the anticaking
      agents improved its chemical stability. However, corn starch and calcium stearate
      had the least adverse effect on chemical stability. Dissolution rate and pH were
      also important factors affecting the chemical and physical stability of the
      powders. Therefore, monitoring storage environmental conditions and anticaking
      agent usage are important for understanding the stability of vitamin C. PRACTICAL
      APPLICATION: Anticaking agent type and ratio significantly affected the physical
      and chemical stability of vitamin C over time and over a range of RHs. No
      anticaking agent improved the chemical stability of the vitamin, and most caused
      an increase in chemical degradation even if physical stability was improved. It
      is possible that anticaking agents would greatly affect other chemically labile
      deliquescent ingredients, and therefore, anticaking agent usage and storage
      conditions should be monitored in blended powder systems.

PMID- 22417545
TI  - Effect of temperature and some added compounds on the stability of blood orange
      marmalade.
AB  - Jams and marmalades are often wrongly believed to be stable products, as the
      degradation of pigments such as anthocyanins, browning reactions, and the
      formation of sugar degradation products may occur during storage. The paper aims
      at studying some of the degradation reactions occurring in blood orange marmalade
      stored at 20  degrees C and 35  degrees C. The addition of natural (tea extract)
      and naturally occurring (ascorbic acid, cysteine, gallic acid) compounds to
      marmalade was addressed at investigating the possible effect on retarding such
      phenomena. Results highlight the dependence of anthocyans and 5-hydroxymethyl-2
      furaldehyde (HMF) levels on the storage temperature. Marmalades added with
      cysteine, unlike the samples added with phenol compounds, showed higher
      anthocyans and lower HMF levels just after processing, together with a reduced
      anthocyan loss kinetics and a slowdown of HMF formation during storage at both
      temperatures. PRACTICAL APPLICATION: Transformation of blood oranges into
      marmalade represents an alternative to fresh market in periods when the high
      availability of the citrus causes the collapse of prices. Blood orange marmalade
      is characterized by a high nutritional value, however, it is not widely
      distributed yet. Its storability is limited by color and organoleptic changes
      that influence consumers' acceptance. The optimization of blood orange marmalade
      preparation could help producers improve storability and widen distribution.

PMID- 22417546
TI  - Metastable radicals and intrinsic chemiluminescence from soy proteins.
AB  - Chemiluminescence from various powdered food proteins were examined without the
      addition of any external source of free radicals or luminescent agents. In the
      solid-state, soy and whey proteins produced more intrinsic chemiluminescence than
      casein, sodium caseinate, or egg albumin. However, when these same food proteins
      were hydrated, intrinsic chemiluminescence from soy proteins was about 4- to 8
      times greater than other source proteins. Quenching the alkyl-radicals in the
      powdered soy proteins with hydrogen sulfide reduced the typical electron
      paramagnetic resonance spectra from soy proteins below detectable levels, and
      reduced the chemiluminescence from the hydrated soy proteins by about 65%.
      Antioxidants also reduced chemiluminescence in hydrated soy proteins by about 50%
      to 92%, with ellagic acid being the most effective. The reduction in
      chemiluminescence from both quenching radicals in the solid state, and by the
      addition of antioxidants to aqueous mixtures, indicate that the chemiluminescence
      produced when soy proteins are hydrated is a free radical catalyzed event. Based
      on the production of chemiluminescence, the radicals from soy protein were
      largely released within 30 min of hydration at 23  degrees C. Elevating the
      hydration temperatures increased chemiluminescence by as much as 280% at 70 
      degrees C, and decreased the half-life of the light-emitting reaction by about 9
      fold. PRACTICAL APPLICATIONS: Levels of metastable radicals in powdered soy
      proteins typically range from to 10 to 100 times greater than free radicals from
      other food protein sources. This research focuses on the types of reactions these
      radicals catalyze when soy proteins are hydrated, and the radicals suddenly
      become reactive. The findings suggest that a portion of the energy released from
      metastable radicals when powdered soy proteins are hydrated is involved in the
      generation of chemically-induced light.

PMID- 22417547
TI  - Optimization of the enzymatic hydrolysis of Blue shark skin.
AB  - Enzymatic hydrolysis of Blue shark skin using ProtamexTM was evaluated seeking
      optimal process conditions. The influence of temperature (45 to 65  degrees C),
      pH (6.8 to 8), and enzyme/substrate ratio (E/S; 1% to 5%) on the responses of
      degree of hydrolysis and protein recovery were determined and process
      optimization was performed looking for maximum value of the responses. Optimum
      conditions were established (T = 51  degrees C, E/S = 4%, and pH = 7.1) and model
      validation was accomplished by triplicate. Under these conditions protein
      hydrolysates were prepared and characterized by their amino acid composition,
      peptide size distribution, and antioxidant capacity by ferric reducing
      antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC)
      assays. A degree of hydrolysis of 19.3% and protein recovery of 90.3% were
      obtained at optimal conditions. Chemical score indicated that the hydrolysate
      supplies minimal essential amino acid requirements for adults. Molecular weight
      of peptides on the hydrolysate was below 6.5 kDa. Enzymatic hydrolysis process
      was efficient for recovery of low molecular weight peptides with important
      nutritional content and antioxidant activity (FRAP = 12 MUmol eq. in
      FeSO(4).7H(2)O/g of protein, TEAC = 225.3 MUmol eq. in trolox/g of protein).

PMID- 22417548
TI  - Levels of glutathione and related enzymes in yellowtail fish muscle subjected to
      ice storage in a modified atmosphere.
AB  - We investigated the effects of ice storage in a modified atmosphere on levels of
      glutathione (GSH) and its related enzyme activities, the metmyoglobin to total
      myoglobin ratio (metMb%), and the K value (a freshness index) of yellowtail fish
      muscle. GSH in ordinary muscle (fast skeletal muscle) as well as in dark muscle
      (slow skeletal muscle) stored in air decreased. GSH in those muscles was almost
      unchanged during storage when packaged with an oxygen absorber or with an oxygen
      absorber-CO(2) generator. Glutathione disulfide in each type of packaging
      remained at low concentrations during storage. The GSH peroxidase activities of
      ordinary muscle and of dark muscle after 7 d of storage in air were lower than
      when packaged with the oxygen absorber or with the oxygen absorber-CO(2)
      generator. The GSH reductase (GR) activities of ordinary muscle at the 4th and
      7th day of storage when packaged with the oxygen absorber showed a tendency to be
      lower than when stored in air. The GR activity of dark muscle in each type of
      packaging method was unchanged during storage. The packaging method did not
      influence the K values of either the ordinary muscle or the dark muscle during
      storage. The metMb% of dark muscle when packaged with the oxygen absorber was
      lower than in the other types of packaging during storage. Therefore, packaging
      with the oxygen absorber is an effective method to prevent the loss of GSH in
      fish meat as well as to reduce the discoloration during storage. PRACTICAL
      APPLICATION: This study examined whether modified atmosphere packaging preserves
      the level of GSH, which is unstable to oxidative stress, in fish muscle. The use
      of an oxygen absorber for packaging can allow us to take in a sufficient amount
      of the bioactive compound from fish meat after storage as well as fresh fish.

PMID- 22417549
TI  - Comparative analysis of the chemical composition and antioxidant activity of red
      (Psidium cattleianum) and yellow (Psidium cattleianum var. lucidum) strawberry
      guava fruit.
AB  - Strawberry guava (Psidium cattleianum Sabine) is a native fruit of Brazil widely
      consumed fresh and used in the food industry. In this context, the present study
      deals with the chemical characterization and the antioxidant activity of the red
      (Psidium cattleianum) and yellow (P. cattleianum var. lucidum Hort.) strawberry
      guava fruits, cultivars Irapua and Ya-Cy, respectively. Knowledge of chemical
      composition is fundamental to human nutrition, contributing to the quality of
      foods. Phenolic compounds in both fruits were analyzed by HPLC-DAD and the total
      flavonoid content was determined by the Folin-Ciocalteu assay. The antioxidant
      activity was evaluated by the total reactive antioxidant (TRAP) method. Psidium
      cattleianum presented a higher content of polyphenolic compounds than P.
      cattleianum var. lucidum (501.33 and 292.03 mg/100 g, respectively), with
      hyperoside being one of the major flavonoids identified for both cultivars. In
      addition to flavonoids, P. cattleianum presented an anthocyanin, identified as
      cyanidin. The antioxidant activity varied in a concentration-dependent manner for
      both strawberry guava species. The volatile oils in fruits and fatty acids in
      seeds were quantified by GC-EM. The analysis of the essential oil of yellow
      strawberry guava was compared with a previous study on the red cultivar,
      revealing beta-caryophyllene as the main component in both oils. The fatty acid
      composition was also quite similar and was especially characterized by the
      presence of unsaturated fatty acids (86.25% and 76%, respectively), among which
      linoleic acid as the most abundant. PRACTICAL APPLICATION: In this study, the
      chemical characterization and the antioxidant activity of the red (Psidium
      cattleianum) and yellow (P. cattleianum var. lucidum Hort.) strawberry guava
      fruits were investigated. This is important for potential application of
      strawberry guava as functional food. Moreover, it may be the experimental basis
      for further development and use in food industry.

PMID- 22417550
TI  - Evaluation of green tea extract as a glazing material for shrimp frozen by
      cryogenic freezing.
AB  - Solutions of green tea (Camellia sinensis) extract (GTE) in distilled water were
      evaluated as a glazing material for shrimp frozen by cryogenic freezing. Total of
      2%, 3%, and/or 5% GTE solutions (2GTE, 3GTE, 5GTE) were used for glazing.
      Distilled water glazed (GDW) and nonglazed shrimp (NG) served as controls. The
      GTE was characterized by measuring color, pH, (o) Brix, total phenols, and %
      antiradical activity. Individual catechins were identified by HPLC. The freezing
      time, freezing rate, and energy removal rate for freezing shrimp by cryogenic
      freezing process were estimated. The frozen shrimp samples were stored in a
      freezer at -21  degrees C for 180 d. Samples were analyzed for pH, moisture
      content, glazing yield, thaw yield, color, cutting force, and thiobarbituric acid
      reactive substances (TBARS) after 1, 30, 90, and 180 d. The HPLC analysis of GTE
      revealed the presence of catechins and their isomers and the total polyphenol
      content was 148.10 +/- 2.49 g/L. The freezing time (min) and energy removal rate
      (J/s) were 48.67 +/- 2.3 and 836.67 +/- 78.95, respectively. Glazed samples had
      higher moisture content compared to NG shrimp after 180 d storage. GTE was
      effective in controlling the lipid oxidation in shrimp. Glazing with GTE affected
      a* and b* color values, but had no significant effect on the L* values of shrimp.

PMID- 22417551
TI  - Gelation, oxygen permeability, and mechanical properties of mammalian and fish
      gelatin films.
AB  - The objective of this study was to evaluate the gelation, thermal, mechanical,
      and oxygen permeability properties of different mammalian, warm- and cold-water
      fish gelatin solutions and films. Mammalian gelatin solutions had the highest gel
      set temperatures, followed by warm-water fish and then cold-water fish gelatin
      solutions. These differences were related to concentrations of imino acids
      present in each gelatin, with mammalian gelatin having the highest and cold-water
      fish gelatin having the lowest concentrations. Mammalian and warm-water fish
      gelatin films contained helical structures, whereas cold-water fish gelatin films
      were amorphous. This was due to the films being dried at room temperature (23 
      degrees C), which was below or near the gelation temperatures of mammalian and
      warm-water fish gelatin solutions and well above the gelation temperature of cold
      water fish gelatin solutions. Tensile strength, percent elongation, and puncture
      deformation were highest in mammalian gelatin films, followed by warm-water fish
      gelatin film and then by cold-water fish gelatin films. Oxygen permeability
      values of cold-water fish gelatin films were significantly lower than those for
      mammalian gelatin films. These differences were most likely due to higher
      moisture sorption in mammalian gelatin films, leading to higher oxygen
      diffusivity.

PMID- 22417552
TI  - Inactivation of vegetative cells by continuous high-pressure processing: new
      insights on the contribution of thermal effects and release device.
AB  - Dynamic or continuous high-pressure processing of fluid foods has drawn
      significant interest as a microbial reduction process in the past decade, and
      many attempts have been made to better understand the mechanisms involved in that
      reduction. This study was intended to provide insight into the contributions of
      thermal effects and differences in pressure release components in the
      inactivation of 2 vegetative pathogen analogs--the Gram-positive Listeria innocua
      and the Gram-negative Escherichia coli. Fluids containing microbial loads of
      10(8) or greater were subjected to continuous high-pressure processing at 200 to
      210 MPa. Without active cooling of the release components, all fluids experienced
      a temperature rise in excess of 70  degrees C, thus occluding any pressure
      related effects for all release components. Active cooling of the valve bodies of
      the 2 valve-style release components (a conical disruption valve and a
      micrometering valve) allowed the temperature rise to be abated enough to isolate
      the effects unique to a given valve. In Tryptic soy broth trials, the mean
      inactivation levels of E. coli between valves were similar--5.16 log and 5.33 log
      for the micrometering and conical disruption valves, respectively. When repeated
      with L. innocua, a similar inactivation level was observed in the conical
      disruption valve (5.1 log) but not the micrometering valve (3.02). Listeria
      innocua trials were also repeated using fluid whole milk, which showed a lower
      levels of inactivation--2.04 log for the micrometering valve and 2.51 log for the
      conical valve. PRACTICAL APPLICATIONS: This paper compares some of the most
      common pressure release components used in continuous high-pressure processing
      and attempts to isolate the contributions of thermal effects from those of
      pressure and shear. This information is important to those seeking to compare and
      evaluate the effectiveness of a proposed set of process parameters for microbial
      inactivation. Further, the ability to reduce the extreme nature of the
      temperature rise has the potential to expand the use of process into more
      temperature sensitive products.

PMID- 22417553
TI  - Angelica acutiloba root alleviates advanced glycation end-product-mediated renal
      injury in streptozotocin-diabetic rats.
AB  - Angelica acutiloba root, a Japanese species of Dong quai being cultivated in
      Hualien County in eastern Taiwan, is used primarily for gynecological disorders
      in women. Increasing evidence indicates that advanced glycation end-products
      (AGEs) contribute to the pathogenesis of diabetic nephropathy. We investigated
      whether A. acutiloba root is beneficial in the amelioration of AGE-mediated renal
      injury in a diabetic rat model. Streptozotocin (STZ)-diabetic rats were treated
      orally with A. acutiloba root extract (AARE) [50, 100, 200 mg/(kg * day)] for 8
      wk. Changes in renal function-related parameters in plasma and urine were
      analyzed at the end of the study. Kidneys were isolated for enzyme immunoassay,
      pathology histology, immunohistochemistry, and Western blot analyses.
      Polyphenolic compounds and flavonoids were abundant in AARE. AARE [200 mg/(kg *
      day)] partially decreased the high plasma glucose level in diabetic rats.
      Diabetic-dependent alterations in urinary albumin, 24-h urinary albumin excretion
      rate, creatinine clearance, and glomerular mesangial matrix expansion were
      ameliorated by AARE treatment. The increased expression of nuclear factor-kappaB,
      transforming growth factor-beta(1), and the progressive accumulation of
      fibronectin in kidney of diabetic rats were attenuated by AARE treatment. AARE
      treatment ameliorated the elevated levels of advanced glycation end products
      (AGEs) and mitochondrial thiobarbituric acid-reactive substance, as well as the
      elevated levels of Nepsilon-(carboxymethyl)lysine and receptors for AGEs in
      kidneys of diabetic rats. The results show that A. acutiloba root has an anti
      diabetic property that involves antihyperglycemia accompanied by amelioration of
      glycation-mediated renal damage.

PMID- 22417555
TI  - Efficacy of cold-pressed terpeneless Valencia oil and its primary components on
      inhibition of Listeria species by direct contact and exposure to vapors.
AB  - This study used disk diffusion assays to evaluate the effectiveness of cold
      pressed terpeneless Valencia oil (CPTVO) and its primary components (linalool,
      citral, and decanal) at inhibiting Listeria via direct contact or exposure to
      vapors. In general, all Listeria strains tested responded similarly to CPTVO and
      its components. Direct contact with linalool produced zones of inhibition that
      were significantly smaller (P < 0.0001) than those associated with all other
      antimicrobials tested. Zones of inhibition for sealed plates were significantly
      larger (P < 0.0001) than those observed for unsealed plates, although the method
      for sealing the plates was insignificant. Exposure to CPTVO vapors resulted in
      zones of inhibition that were significantly smaller than those resulting from
      decanal vapors (P < 0.0001). The difference observed between the zones of
      inhibition produced by antimicrobial exposure via vapors or direct contact was
      only slightly significant (P = 0.02). Antimicrobial essential oil (EO) vapors may
      be an effective alternative to direct contact EOs to safely and effectively
      inhibit microorganisms while minimizing undesired organoleptic changes sometimes
      associated with EO contact. CPTVO and its primary components, decanal and citral,
      may have potential in the food industry as all natural, generally recognized as
      safe antimicrobials used in modified atmosphere packaging designed to inhibit
      Listeria without requiring direct contact with food products.

PMID- 22417554
TI  - Cruciferous vegetable phytochemical sulforaphane affects phase II enzyme
      expression and activity in rat cardiomyocytes through modulation of Akt signaling
      pathway.
AB  - The isothiocyanate sulforaphane (SF), abundant in Cruciferous vegetables, is
      known to induce antioxidant/detoxification enzymes in many cancer cell lines, but
      studies focused on its cytoprotective action in nontransformed cells are just at
      the beginning. Since we previously demonstrated that SF elicits cardioprotection
      through an indirect antioxidative mechanism, the aim of this study was to analyze
      the signaling pathways through which SF exerts its protective effects. Using
      cultured rat cardiomyocytes, we investigated the ability of SF to activate
      Akt/protein kinase B (PKB) and extracellular signal-regulated kinase 1 and 2
      (ERK1/2) signaling pathways, which are implicated in cardiac cell survival, and
      to increase the phosphorylation of Nuclear factor E2-related factor 2 (Nrf2) and
      its binding to the antioxidant response element. By means of specific inhibitors,
      we demonstrated that the Phosphatidylinositol 3-kinase (PI3K)/Akt pathway
      represents a mechanism through which SF influences both expression and activity
      of glutathione reductase, glutathione-S-transferase, thioredoxin reductase, and
      NAD(P)H:quinone oxidoreductase-1, analyzed by western immunoblotting and
      spectrophotometric assay, respectively, and modulates Nrf2 binding and
      phosphorylation resulting in a cytoprotective action against oxidative damage.
      Results of this study confirm the importance of phase II enzymes modulation as
      cytoprotective mechanism and support the nutritional assumption of Cruciferous
      vegetables as source of nutraceutical cardioprotective agents.

PMID- 22417556
TI  - Use of Taiwanese ropy fermented milk (TRFM) and Lactococcus lactis subsp.
      cremoris isolated from TRFM in manufacturing of functional low-fat cheeses.
AB  - The purpose of this study was to manufacture new functional low-fat cheeses using
      Taiwanese ropy fermented milk (TRFM) and Lactococcus lactis subsp. cremoris
      strains isolated from TRFM. After 28 d of ripening and storage, the viable
      populations of lactic acid bacteria (LAB) in the low-fat cheeses made with L.
      lactis subsp. cremoris TL1 (TL1), L. lactis subsp. cremoris TL4 (TL4), and TRFM
      still maintained above 10(8) CFU/g. The low-fat cheeses made with TL1 and TRFM
      showed higher moisture contents than the cheeses made with TL4, full-fat, and low
      fat cheese controls. The low-fat cheeses made with TL1 and TL4 had higher
      customer preferential scores similar to full-fat cheese control in the sensory
      evaluation. Additionally, the low-fat cheeses fermented with TL1, TL4, and TRFM
      for 4 h had higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging
      and ferrous ion-chelating abilities than the cheeses fermented with the starters
      for 8 h, full-fat, and low-fat cheese controls. A better angiotensin-converting
      enzyme (ACE) inhibition activity was also observed in the low-fat cheeses made
      with TL1, TL4, and TRFM than that in the full-fat and low-fat cheese controls
      during ripening and storage period. PRACTICAL APPLICATION: As health-conscious
      consumers continue to seek low-fat alternatives in their diets, there remain
      strong interests for the dairy industry to develop low-fat cheeses to meet the
      demands. This study clearly demonstrated that the low-fat cheeses fermented with
      TL1 for 4 h showed a better overall acceptability and possessed antioxidative
      abilities and ACE inhibitory activities than other cheeses tested in this study.
      By improving its flavor and investigating the possible mechanisms of its
      functionalities in the future, this low-fat cheese might possibly be
      commercialized and give a positive impact on cheese consumption in the future.

PMID- 22417557
TI  - Internal transcribed spacer as a target to assess yeast biodiversity in Italian
      Taleggio PDO cheese.
AB  - Three batches of soft smear-ripened Taleggio PDO cheese were made in Northern
      Italy during the summertime 2010. A total of 129 isolates cultured from cheese
      surface were examined by using PCR-based methods and sequencing of both the ITS1
      region and D1 and D2 domains of the 26S rRNA gene. Sequence analysis of isolates
      brought to the identification of 6 species: Debaryomyces hansenii, Kluyveromyces
      lactis, Kluyveromyces marxianus, Yarrowia lipolytica, Pichia guilliermondii, and
      Torulaspora delbrueckii. Analysis of DNA directly extracted from 45 cheese
      surfaces permitted to detect 2 additional species Candida sake and Candida
      etchellsii. D. hansenii was predominant and widespread whereas the other yeast
      species were detected less frequently. To determine the relationships between
      yeast community and the environment, 39 isolates from wooden boxes used for dry
      salting of cheese were analyzed as well. Sequencing of ITS1 region allowed to
      identify D. hansenii, T. delbrueckii, and K. lactis. ITS1 multiple sequence
      alignments of D. hansenii detected in wooden boxes showed an in-del polymorphism
      at position 169. ITS1 secondary structures of yeasts were modeled to explore new
      applications of this region for molecular identification purposes. PRACTICAL
      APPLICATION: This study used molecular analysis to identify adventitious yeast
      population present in the surface of Taleggio smear-ripened cheese. D. hansenii
      was found predominant in pasteurized milk, in dry salting equipment, and in all
      cheese samples until the end of ripening.

PMID- 22417558
TI  - Effect of grape pomace extracts obtained from different grape varieties on
      microbial quality of beef patty.
AB  - Grape pomace extracts were obtained from 5 different grape varieties grown in
      Turkey. The extracts were concentrated to obtain crude extracts; and incorporated
      into beef patties at 0% (Control), 1%, 2%, 5%, and 10% concentrations to test
      their antimicrobial effects in different storage periods (first, 12, 24, and 48
      h). The numbers of microorganism were generally decreased by the extract
      concentration during the storage period. All the microorganisms tested were
      inhibited by the extract concentration of 10% in all the storage periods.
      Furthermore, the foodborne pathogens including Enterobacteriaceae and coliform
      bacteria, and the spoilage microorganisms including yeasts and moulds and
      lipolytic bacteria were also inhibited by 5% of Emir, Gamay, and Kalecik Karasi
      varieties in beef patties. Considering the results, the extracts of grape pomaces
      might be a good choice in the microbial shelf life extension of the food products
      as well as inhibiting the food pathogens as the case of beef patties. PRACTICAL
      APPLICATION: Grape pomace consists of seeds, skins, and stems, and an important
      by-product that is well known to be the rich source of phenolic compounds, both
      flavonoids and non-flavonoids. These substances have considerable beneficial
      effects on human health. The use of natural antimicrobial compounds, like plant
      extracts of herbs and spices for the preservation of foods has been very popular
      issue because of their antimicrobial activity. Therefore, grape pomace should be
      added into some food formulations to benefit from their protective effects. In
      this respect, this study reports the effect of addition of grape pomace extracts
      obtained from different grape varieties on microbial quality of beef patty. The
      results obtained in this study may be useful for food industry, which has
      recently tended to use natural antimicrobial sources in place of synthetic
      preservatives to prevent microbial spoilage.

PMID- 22417559
TI  - Physiological, volatile, and SEM surface effects resulting from cutting and
      dipping treatments in cantaloupe.
AB  - Previous research examined sanitation treatments on cut cantaloupe tissue to
      deliver germicidal and food safety effects. However, an apparent compromise
      between volatile loss and treatment/sampling efficacy appeared. Subsequently, a
      physiological and volatile reassessment of thinly sliced tissue against cubes was
      performed in cantaloupe tissue. Thin sliced cantaloupe L* decreased 27.5%, 40.5%,
      and 52.9% in 3, 2, and 1 mm thickness, respectively, compared with cut cubes
      after 3 d. Overall color (C) decreased in freshly prepared cubes (2.4%) and
      slices (14.4%) that were washed in cold water. Surface area per unit volume (SA:
      vol) in slices was 4.1 times greater than typical cubes, as reflected by
      substantial water loss (20.4%, 9.5%, and 6.7% in 1, 2 and 3-mm slices,
      respectively) after 1 d at 5  degrees C. Rinsing cubes and thin-slices with 5 
      degrees C deionized water resulted in roughly 15% soluble solids loss. SEM
      indicated 65.4% reduced cell size in 1-d old thin slices, evidenced by excessive
      cell damage and desiccation compared with stored fresh-cut cubes. In thin-sliced
      tissue exposed 15 min to an open atmosphere (mimic sanitation treatments), total
      esters decreased 92.8% and 95.8%, respectively, after 1 and 3 d storage at 5 
      degrees C. Washing tissue provided a boundary layer that reduced short-term ester
      losses in slices and cubes. Excessive cutting, sanitation treatment regimes, and
      storage can radically alter the desirable volatile profile of cut cantaloupe.
      Reduction of tissue size to maximize food-safety sanitation efficacy or
      delivering items to a niche market will need substantial work to engineer
      equipment and develop protocols to insure that product quality and volatiles are
      not compromised. PRACTICAL APPLICATION: We have demonstrated that cutting method
      and sampling protocol are critically important when using volatiles as a means by
      which to assess or interpret stress response and ascribe fresh-cut quality.
      Reduction of tissue size to maximize food-safety sanitation efficacy (for
      example, thin slices) will need substantial work to engineer equipment and design
      protocols to insure product quality and volatile profiles are not compromised.

PMID- 22417560
TI  - Effect of freezing temperature on the color of frozen salmon.
AB  - New freezing methods developed with the purpose of improved product quality after
      thawing can sometimes be difficult to get accepted in the market. The reason for
      this is the formation of ice crystals that can give the product a temporary color
      loss and make it less appealing. We have here used microscopy to study ice
      crystal size as a function of freezing temperature by investigating the voids in
      the cell tissue left by the ice crystals. We have also investigated how freezing
      temperature affects the color and the visible absorption spectra of frozen
      salmon. Freezing temperatures previously determined to be the best for quality
      after thawing (-40 to -60  degrees C) were found to cause a substantial loss in
      perceived color intensity during frozen state. This illustrated the conflict
      between optimal freezing temperatures with respect to quality after thawing
      against visual appearance during frozen state. Low freezing temperatures gave
      many small ice crystals, increased light scattering and an increased absorption
      level for all wavelengths in the visible region. Increased astaxanthin
      concentration on the other hand would give higher absorption at 490 nm. The
      results showed a clear potential of using visible interactance spectroscopy to
      differentiate between poor product coloration due to lack of pigmentation and
      temporary color loss due to light scattering by ice crystal. This type of
      measurements could be a useful tool in the development of new freezing methods
      and to monitor ice crystal growth during frozen storage. It could also
      potentially be used by the industry to prove good product quality. PRACTICAL
      APPLICATION: In this article we have shown that freezing food products at
      intermediate to low temperatures (-40 to -80  degrees C) can result in paler
      color during frozen state, which could affect consumer acceptance. We have also
      presented a spectroscopic method that can separate between poor product color and
      temporary color loss due to freezing.

PMID- 22417561
TI  - Total phenolic content, consumer acceptance, and instrumental analysis of bread
      made with grape seed flour.
AB  - Grape seed flour (GSF) from grape pomace, a waste product generated during
      winemaking, was explored for use in bread production due to its potential health
      benefits. This study evaluated the consumer acceptance and physical properties of
      bread, including total phenolic content (TPC), made with varying levels of GSF.
      Dough and breads were prepared using different levels of replacement of hard red
      spring wheat flour (HRS) with GSF (0 to 10 g GSF/100 g HRS) and stored for 0, 2,
      or 6 wk at -20  degrees C. Replacement of 10 g GSF/100 g HRS increased the bread
      TPC from 0.064 mg tannic acid/g dry weight to 4.25 mg tannic acid/g dry weight.
      Consumer acceptance and instrumental analyses were used to investigate changes in
      sensory and texture properties due to GSF replacement. Replacement above 5 g
      GSF/100 g HRS decreased the loaf brightness and volume, with an increase in the
      bread hardness and porosity. Generally, breads containing >= 7.5 g GSF/100 g HRS
      were characterized by lower consumer acceptance. A reduction in overall and
      bitterness acceptance was observed in bread at 10 g GSF/100 g HRS, with decreased
      acceptance of astringency and sweetness at 7.5 and 10 g GSF/100 g HRS. Based on
      these results, the replacement of 5 g GSF/100 g HRS is recommended for the
      production of fortified breads with acceptable physical and sensory properties
      and high TPC activity compared to refined bread. PRACTICAL APPLICATIONS: This
      study shows that grape seed flour (GSF) can be used to replace hard red spring
      wheat flour (HRS) in bread production, with moderate impact on the physical and
      sensory properties of the bread. Replacement of up to 10 g GSF/100 g HRS
      significantly decreased overall consumer acceptance of the bread, with lower
      consumer acceptance of sweetness and astringency at 7.5 and 10 g GSF/100 g HRS.
      Thus, a replacement value of 5 g GSF/100 g HRS is recommended for the production
      of fortified breads.

PMID- 22417562
TI  - Chemical stability of extra-virgin olive oil added with oregano essential oil.
AB  - Extra virgin olive oil is highly consumed and well known for its nutritional and
      health benefits. However, it is fatty food highly susceptible to lipid oxidation.
      The objective of this study was to evaluate the preserving effect of oregano
      (Origanum vulgare L. spp vulgare called "oregano compacto") essential oil on
      physical and chemical properties in extra virgin olive oil during storage.
      Oregano essential oil composition was analyzed by GC-MS. This essential oil was
      added into extra virgin olive oil at 0.05%. The samples were stored in 3
      different conditions: darkness, light exposure, and temperature (60  degrees C).
      Chemical indicators of lipid oxidation (peroxide value, p-anisidine value,
      conjugated dienes, free fatty acidity, and carotenoid and chlorophyll contents)
      were measured. High content in carvomenthol (22.52%), terpinolene (19.77%),
      thymol (13.51%), and gamma-terpinene (10.30%) were detected in oregano essential
      oil. Olive oil samples without oregano essential oil stored at 60  degrees C and
      exposure at artificial light had the highest peroxide values during storage.
      Higher p-anisidine and K232 values after day 7 of storage were detected in
      temperature, darkness, and light exposure treatments. Light treatment was the
      main factor that degraded chlorophyll causing loss of color. The highest
      chlorophyll content (3.87 mg/kg) was observed in olive oil with essential oil at
      the end of storage. In general, olive oil samples added with oregano essential
      oil had lower peroxide, conjugated dienes, and p-anisidine values and higher
      chlorophyll and carotenoid contents during storage. Oregano essential oil retards
      lipid oxidation process in olive oil prolonging its shelf life. PRACTICAL
      APPLICATION: Oregano essential oil was and is used with the purpose of flavoring
      and aromatizing food. This essential oil due to its composition has shown
      antioxidant activity. Synthetic antioxidants such as butylated hydroxytoluene
      (BHT) and butylated hydroxyanisole (BHA) are thought to be promoters of
      carcinogenesis. Extra virgin olive oil is widely consumed because of its
      nutritional benefits and sensory properties which are very important to be
      preserved in the product. In this study, the oregano essential oil showed
      remarkable antioxidant activity in olive oil. Therefore, this essential oil could
      be considered for the industry as natural antioxidant not only to be used in
      olive oil but also in other fatty food products to substitute synthetic ones.

PMID- 22417563
TI  - Preferences for berries among consumers in southern Chile: blueberries are
      produced but are they consumed?
AB  - Blueberry plantations in Chile are oriented exclusively towards exports to
      northern hemisphere countries; however, this fruit has recently been introduced
      into the domestic market due to the increased supply and a fall in export market
      prices. Based on the previously mentioned, the objectives of the present study
      were to evaluate consumer preferences for 3 species of berries (blueberries,
      strawberries, and raspberries), sold loose (unpackaged) as opposed to packaged
      and branded, at different prices, in one of the principal blueberry producing
      areas of Chile; and to distinguish consumer segments by their preferences. To do
      this a survey was applied to 400 people in the Araucania Region of southern
      Chile, who were responsible for purchasing fruit for their households. Conjoint
      analysis showed a preference for raspberries and strawberries over blueberries,
      packaged and branded, at the lowest price. Total of 2 principal segments were
      distinguished by cluster analysis: "price sensitive" (42.7%), who preferred
      strawberries, and "sensitive to species of berry" (47.5%), who preferred
      raspberries and strawberries. The segments presented different profiles in their
      demographic make-up and fruit consumption behavior. Strategies are discussed that
      might reverse the low acceptance of blueberries in the Chilean domestic market.
      PRACTICAL APPLICATION: This study presents information on the introduction of new
      fresh foods into the market.

PMID- 22417564
TI  - Antioxidant and antiproliferation effects of extractable and nonextractable
      polyphenols isolated from apple waste using different extraction methods.
AB  - Fruits and vegetables waste byproducts could be utilized as a good source of
      cheap antioxidants for improving human health and reducing the risks of some
      chronic diseases. Results from examining industrial apple waste revealed that the
      total polyphenolic content in nonextractable polyphenols (NEPPs) reached 539.84
      +/- 8.90 mg as gallic acid equivalents/1 g of dry wt. in comparison to 77.26 +/-
      11.53 mg dry wt. of extractable polyphenols (EPPs). The antioxidant activities of
      NEPPs reported as percentage reduction in 2,2-Diphenyl-1-picrylhydrazyl and 2'.2'
      azinobis(3-ethylbenzothiazline-6-sulfonic acid) diammonium salt were 89.76 +/-
      0.93% and 99.78 +/- 0.38%, respectively. In addition, the antiproliferation study
      on human HeLa, HepG2, and HT-29 cancer cells showed that NEPPs at the
      concentration of 1 mg/mL had significant inhibitory effects against all tested
      cancer cells (46.2% to 95%), where EPP showed lower effect (3.9% to 22.2%). These
      results clearly indicated that NEPPs from industrial apple waste could be a good
      source of natural antioxidants with significant antiproliferation efficacy
      against human cancer cells.

PMID- 22417567
TI  - Clinical decision-making to facilitate appropriate patient management in
      chiropractic practice: 'the 3-questions model'.
AB  - BACKGROUND: A definitive diagnosis in chiropractic clinical practice is
      frequently elusive, yet decisions around management are still necessary. Often, a
      clinical impression is made after the exclusion of serious illness or injury, and
      care provided within the context of diagnostic uncertainty. Rather than focussing
      on labelling the condition, the clinician may choose to develop a defendable
      management plan since the response to treatment often clarifies the diagnosis.
      DISCUSSION: This paper explores the concept and elements of defensive problem
      solving practice, with a view to developing a model of agile, pragmatic decision
      making amenable to real-world application. A theoretical framework that reflects
      the elements of this approach will be offered in order to validate the potential
      of a so called '3-Questions Model'; SUMMARY: Clinical decision-making is
      considered to be a key characteristic of any modern healthcare practitioner. It
      is, thus, prudent for chiropractors to re-visit the concept of defensible
      practice with a view to facilitate capable clinical decision-making and competent
      patient examination skills. In turn, the perception of competence and
      trustworthiness of chiropractors within the wider healthcare community helps
      integration of chiropractic services into broader healthcare settings.

PMID- 22417568
TI  - Tuberculous pleural effusion.

PMID- 22417569
TI  - Heated and humidified high-flow oxygen therapy reduces discomfort during
      hypoxemic respiratory failure.
AB  - BACKGROUND: Non-intubated critically ill patients are often treated by high-flow
      oxygen for acute respiratory failure. There is no current recommendation for
      humidification of oxygen devices. METHODS: We conducted a prospective randomized
      trial with a final crossover period to compare nasal airway caliber and
      respiratory comfort in patients with acute hypoxemic respiratory failure
      receiving either standard oxygen therapy with no humidification or heated and
      humidified high-flow oxygen therapy (HHFO2) in a medical ICU. Nasal airway
      caliber was measured using acoustic rhinometry at baseline, after 4 and 24 hours
      (H4 and H24), and 4 hours after crossover (H28). Dryness of the nose, mouth, and
      throat was auto-evaluated and assessed blindly by an otorhinolaryngologist. After
      the crossover, the subjects were asked which system they preferred. RESULTS:
      Thirty subjects completed the protocol and were analyzed. Baseline median oxygen
      flow was 9 and 12 L/min in the standard and HHFO2 groups, respectively (P = .21).
      Acoustic rhinometry measurements showed no difference between the 2 systems. The
      dryness score was significantly lower in the HHFO2 group at H4 (2 vs 6, P = .007)
      and H24 (0 vs 8, P = .004). During the crossover period, dryness increased
      promptly after switching to standard oxygen and decreased after switching to
      HHFO2 (P = .008). Sixteen subjects (53%) preferred HHFO2 (P = .01), especially
      those who required the highest flow of oxygen at admission (P = .05).
      CONCLUSIONS: Upper airway caliber was not significantly modified by HHFO2,
      compared to standard oxygen therapy, but HHFO2 significantly reduced discomfort
      in critically ill patients with respiratory failure. The system is usually
      preferred over standard oxygen therapy.

PMID- 22417570
TI  - Comparative analysis of drug resistance among B and the most prevalent non-B HIV
      type 1 subtypes (C, F, and CRF02_AG) in Italy.
AB  - In recent years, increasing numbers of patients infected with HIV-1 non-B
      subtypes have been treated with modern antiretroviral regimens. Therefore, a
      better knowledge of HIV drug resistance in non-B strains is crucial. Thus, we
      compared the mutational pathways involved in drug resistance among the most
      common non-B subtypes in Italy (F, C, and CRF02_AG) and the B subtype. In total,
      2234 pol sequences from 1231 virologically failing patients from Central Italy
      were analyzed. The prevalence of resistance mutations in protease and reverse
      transcriptase between non-B and B subtypes has been evaluated. Among patients
      treated with nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) and
      with thymidine analogues (TA) experience, TAMs1 M41L and L210W were less
      prevalent in CRF02_AG, while TAMs2 T215F and K219E were more prevalent in the F
      subtype. In NRTI-treated patients having experience with abacavir, didanosine,
      tenofovir, or stavudine the K65R mutation was mostly prevalent in the C subtype.
      In non-NRTI (NNRTI)-treated patients infected by the C subtype the prevalence of
      K103N was lower than in patients infected with other subtypes, while the
      prevalence of Y181C and Y188L was higher compared to subtype B. The prevalence of
      Y181C was higher also in subtype F as compared to subtype B. In patients treated
      with protease inhibitors, L89V was predominantly found in CRF02_AG, while the TPV
      resistance mutation T74P was predominantly found in the C subtype. Some
      differences in the genotypic drug resistance have been found among patients
      infected with B, C, F, and CRF02_AG subtypes in relationship to treatment. These
      results may be useful for the therapeutic management of individuals infected with
      HIV-1 non-B strains.

PMID- 22417571
TI  - Diverse energetic effects of charge reversal mutations of poxvirus topoisomerase
      IB.
AB  - A key aspect of the reaction mechanism of type IB topoisomerases is the
      controlled unwinding of DNA supercoils while the enzyme is transiently bound to
      one strand of the DNA duplex via a phosphotyrosyl linkage. In this complex, the
      mobile segment of the bound DNA downstream from the site of cleavage must rotate
      around the helical axis, requiring that interactions with the enzyme must break
      and re-form multiple times during the course of removing supercoils. A crystal
      structure of variola virus type IB topoisomerase (vTopo) bound to DNA shows
      several positively charged side chains that interact with the downstream mobile
      and upstream rigid segments, suggesting that these groups may play a role in
      catalysis, including the processive unwinding of supercoils. We have mutated
      three such residues, R67, K35, and K271, to Ala and Glu and determined the
      energetic effects of these mutations at each point along the reaction coordinate
      of vTopo. R67 interacts with a phosphate group in the rigid DNA segment across
      from the site of DNA strand cleavage. The ~30-fold damaging effects of the R67A
      and R67E mutations were primarily on the phosphoryl transfer step, with little
      effect on enzyme-DNA binding, or the processivity of supercoil unwinding. Removal
      of the K35 interaction shows mutational effects similar to those of R67, even
      though this residue interacts with the mobile segment 3 bp from the cleavage
      site. The two mutations of K271, which interacts with the mobile region even
      further from the site of covalent linkage, show significant effects not only on
      phosphoryl transfer but also on downstream DNA strand positioning. Moreover,
      supercoil unwinding measurements indicate that the K271A and K271E mutations
      increase the average number of supercoils that are removed during the lifetime of
      the covalent complex, enhancing the processivity of supercoil unwinding. These
      measurements support the proposal that the processivity of supercoil unwinding
      can be regulated by electrostatic interactions between the enzyme and the mobile
      DNA phosphate backbone.

PMID- 22417573
TI  - Margaret McClelland OBE (Australia).

PMID- 22417572
TI  - Genetic diversity and population structure of genes encoding vaccine candidate
      antigens of Plasmodium vivax.
AB  - BACKGROUND: A major concern in malaria vaccine development is genetic
      polymorphisms typically observed among Plasmodium isolates in different
      geographical areas across the world. Highly polymorphic regions have been
      observed in Plasmodium falciparum and Plasmodium vivax antigenic surface proteins
      such as Circumsporozoite protein (CSP), Duffy-binding protein (DBP), Merozoite
      surface protein-1 (MSP-1), Apical membrane antigen-1 (AMA-1) and Thrombospondin
      related anonymous protein (TRAP). METHODS: Genetic variability was assessed in
      important polymorphic regions of various vaccine candidate antigens in P. vivax
      among 106 isolates from the Amazon Region of Loreto, Peru. In addition, genetic
      diversity determined in Peruvian isolates was compared to population studies from
      various geographical locations worldwide. RESULTS: The structured diversity found
      in P. vivax populations did not show a geographic pattern and haplotypes from all
      gene candidates were distributed worldwide. In addition, evidence of balancing
      selection was found in polymorphic regions of the trap, dbp and ama-1 genes.
      CONCLUSIONS: It is important to have a good representation of the haplotypes
      circulating worldwide when implementing a vaccine, regardless of the geographic
      region of deployment since selective pressure plays an important role in
      structuring antigen diversity.

PMID- 22417574
TI  - Optimization of beta-casein stabilized nanoemulsions using experimental mixture
      design.
AB  - The objective of this study was to determine the effect of changing viscosity and
      glass transition temperature in the continuous phase of nanoemulsion systems on
      subsequent stability. Formulations comprising of beta-casein (2.5%, 5%, 7.5%, and
      10% w/w), lactose (0% to 20% w/w), and trehalose (0% to 20% w/w) were generated
      from Design of Experiments (DOE) software and tested for glass transition
      temperature and onset of ice-melting temperature in maximally freeze-concentrated
      state (T(g) ' & T(m) '), and viscosity (MU). Increasing beta-casein content
      resulted in significant (P < 0.0001) increases in viscosity and T(m) ' (P=
      0.0003), and significant (P < 0.0001) decreases in T(g) '. A mixture design was
      used to predict the optimum levels of lactose and trehalose required to attain
      the minimum and maximum T(g) ' and viscosity in solution at fixed protein
      contents. These mixtures were used to form the continuous phase of beta-casein
      stabilized nanoemulsions (10% w/w sunflower oil) prepared by microfluidization at
      70 MPa. Nanoemulsions were analyzed for T(g) ' & T(m) ', as well as viscosity,
      mean particle size, and stability. Increasing levels of beta-casein (2.5% to 10%
      w/w) resulted in a significant (P < 0.0001) increase in viscosity (5 to 156
      mPa.s), significant increase in particle size (P= 0.0115) from 186 to 199 nm, and
      significant decrease (P= 0.0001) in T(g) ' (-45 to -50  degrees C). Increasing
      the protein content resulted in a significant (P < 0.0001) increase in
      nanoemulsion stability. A mixture DOE was successfully used to predict glass
      transition and rheological properties for development of a continuous phase for
      use in nanoemulsions.

PMID- 22417575
TI  - Discrimination of Chinese vinegars based on headspace solid-phase microextraction
      gas chromatography mass spectrometry of volatile compounds and multivariate
      analysis.
AB  - Headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography
      mass spectrometry (GC-MS) was applied for the determination of the characteristic
      volatile profiles of Chinese vinegars. Multivariate statistical techniques, such
      as principal component analysis (PCA) and cluster analysis (CA), were used to
      characterize the different Chinese vinegars by types, fermentation method, and
      production area. A total of 56 volatile compounds were identified, including 15
      esters, 10 aldehydes, 5 acids, 12 alcohols, 5 ketones, 4 volatile phenols, 2
      pyrazines, and 3 miscellaneous compounds. The major compounds in Chinese vinegars
      were furfural, acetic acid, ethyl acetate, 3-hydroxy-2-butanone, 3-methyl-1
      butanol, isopentyl acetate, benzaldehyde, phenylethyl alcohol. The PCA results
      showed that characterizing the Chinese vinegars by HS-SPME-GC-MS was highly
      related to their type, fermentation method, and production area, and all these
      influencing factors were not independent. The CA results indicated that the
      fermentation method had a greater effect than vinegar type and production area.
      The results showed that HS-SPME-GC-MS together with chemometrics could provide
      practical reference for characterization of Chinese vinegars. Practical
      Application:  HS-SPME coupled with GC-MS was applied for the determination of the
      characteristic volatile profiles of Chinese vinegars. The major compounds in
      Chinese vinegars were furfural, acetic acid, ethyl acetate, 3-hydroxy-2-butanone,
      3-methyl-1-butanol, isopentyl acetate, benzaldehyde, phenylethyl alcohol. HS-SPME
      GC-MS together with chemometrics was an efficient tool for evaluating vinegar
      authenticity.

PMID- 22417576
TI  - Underestimation of pyruvic acid concentrations by fructose and cysteine in 2,4
      dinitrophenylhydrazine-mediated onion pungency test.
AB  - Onion pungency has been routinely measured by determining pyruvic acid
      concentration in onion juice by reacting with 2,4-dinitrophenylhydrazine (DNPH)
      since 1961. However, the absorbency of the color adduct of the reaction rapidly
      decreased in onion samples as compared to that of the pyruvic acid standards,
      resulting in underestimations of the pyruvic acid concentrations. By measuring
      the absorbency at 1 min, we have demonstrated that accuracy could be
      substantially improved. As a continuation, the causes of degradation of the color
      adduct after the reaction and pyruvic acid itself before the reaction were
      examined in this study. Alliinase action in juice (fresh or cooked) and bulb
      colors did not influence the degradation. Some organic acids indigenously found
      in onion, such as ascorbic acid, proline, and glutamic acid, did not reduce the
      absorbency. However, fructose within the onion juice or supplemented caused the
      degradation of the color adduct, whereas sucrose and glucose had a lesser effect.
      Degradation rates increased proportionally as fructose concentrations increased
      up to 70 mg/mL. Cysteine was found to degrade the pyruvic acid itself before the
      pyruvic acid could react with DNPH. Approximately 90% of the pyruvic acid was
      degraded after 60 min in samples of 7 mM pyruvic acid supplemented with 10 mg/mL
      cysteine. Spectral comparisons of onion juice containing fructose naturally and
      pyruvic acid solution with supplemented fructose indicated identical patterns and
      confirmed that the color-adduct degradation was caused by fructose. Our study
      elucidated that fructose, a major sugar in onion juice, caused the degradation of
      color adduct in the onion pungency test and resulted in underestimation of the
      pyruvic acid concentration.

PMID- 22417577
TI  - Flow injection assessment of nitrate contents in fresh and cooked fruits and
      vegetables grown in Fiji.
AB  - Nitrates form part of the essential chemistry of soils and plants. Thus, plant
      roots are able to absorb nitrate directly from the soil. It has been discovered
      that human nitrate intake is mainly from vegetables. Vegetables play an important
      role in human nutrition since they are an outstanding source for vitamins,
      minerals, and biologically active compounds. In risk assessment of nitrate
      contents, this study reports the nitrate levels of 8 commonly consumed fruits and
      vegetables grown in Fiji, tomato (Lycopersicon esculentum), eggplant (Solanum
      melongena), capsicum (Capsicum annuum var. grossum), breadfruit (Artocarpus
      altilis), long bean (Vigna sesquipedalis), jackfruit (A. heterophyllus), pumpkin
      (Cucurbita pepo), and cucumber (Cucumis sativus). The effects of different types
      of cooking methods, baking, boiling, and frying, have also been studied. The
      validated flow injection analysis technique has been used to quantify the nitrate
      N levels in the chosen products following nitrate extraction using the activated
      carbon technique. The mean values of nitrate levels in fresh products ranged from
      25.83 to 281.02 mg NO(3) (-)  kg(-1) . The study shows that boiling reduced
      nitrate contents by 65.37% to 25.25%. The frying in soy bean oil elevated nitrate
      contents from 354.79% to 86.69%, but after baking, nitrate contents remained
      almost constant with slight increasing trend in the case of tomato (19.97%). The
      nitrate levels published in the literature for the same types of fruits and
      vegetables studied have also been reviewed and compared. The average nitrate-N
      values were comparable or lower than overseas data, but did not present
      unpredictably high values, that is, they were below the risk level.

PMID- 22417578
TI  - Characterization of ACE-inhibitory peptide associated with antioxidant and
      anticoagulation properties.
AB  - A bioactive peptide Arg-Val-Pro-Ser-Leu (RVPSL) obtained from egg white protein
      was characterized by LC-MS and further chemically synthesized by the Fmoc solid
      phase method and investigated in terms of its angiotensin converting enzyme (ACE)
      inhibitory activity, antioxidant property, and anticoagulation activity, as well
      as its stability in a simulated gastrointestinal digestion. The peptide exhibited
      an ACE-inhibitory activity with an IC(50)  value of 20 MUM. Also, the peptide
      could efficiently quench the (1,1)-diphenyl-2-picrylhydrazyl free radicals and
      exhibit high anticoagulation activity with a complete inhibition at 100 mM.
      Moreover, the peptide has a good stability against protease digestion. These
      results suggest that the peptide RVPSL may have potential to be used in
      nutraceuticals and functional food. Practical Application:  The present research
      revealed a novel multifunctional peptide hydrolyzed from egg white protein. The
      peptide RVPSL was not only able to block the amplification of the coagulation
      cascade, but also able to inhibit ACE activity.

PMID- 22417579
TI  - Characterization of the pulp and kernel oils from Syagrus oleracea, Syagrus
      romanzoffiana, and Acrocomia aculeata.
AB  - Vegetable oils are important sources of essential fatty acids. It is, therefore,
      important to characterize plant species that can be used as new oil sources. This
      study aimed to characterize the oils from guariroba (Syagrus oleracea), jeriva
      (Syagrus romanzoffiana), and macauba (Acrocomia aculeata). The physicochemical
      characterization was performed using official analytical methods for oils and
      fats, free fatty acids, peroxide value, refractive index, iodine value,
      saponification number, and unsaponifiable matter. The oxidative stability was
      determined using the Rancimat at 110  degrees C. The fatty acid composition was
      performed by gas chromatography. The results were submitted to Tukey's test for
      the medium to 5% using the ESTAT program. The pulp oils were more unsaturated
      than kernel oils, as evidenced by the higher refractive index and iodine value,
      especially the macauba pulp oil which gave 1.4556 and 80 g I(2) /100 g,
      respectively, for these indices. The kernel oils were less altered by oxidative
      process and had high induction period, free fatty acids below 0.5%, and peroxide
      value around 0.19 meq/kg. The guariroba kernel oil showed the largest induction
      period, 91.82 h. Practical Application:  The vegetable oils, besides being
      consumed directly as food, are important raw material for the chemical,
      pharmaceutical, and food industries. In recent years, the world market of
      vegetable oils has been characterized by stronger growth of demand over supply.
      Several species of palm trees are shown to be promising sources of oils. The
      characterization of oils extracted from some species, such as guariroba, jeriva,
      and macauba, has not yet been fully elucidated. For this reason, it becomes
      important to investigate the physicochemical characterization of these oils,
      aiming at a possible use in food or in the industry.

PMID- 22417580
TI  - Discrimination between immature and mature green coffees by attenuated total
      reflectance and diffuse reflectance Fourier transform infrared spectroscopy.
AB  - The objective of this work was to evaluate the potential of Fourier transform
      infrared spectroscopy (FTIR) in the characterization and discrimination between
      immature and mature or ripe coffee beans. Arabica coffee beans were submitted to
      FTIR analysis by reflectance readings employing attenuated total reflectance
      (ATR) and diffuse reflectance (DR) accessories. The obtained spectra were
      similar, but in general higher absorbance values were observed for nondefective
      beans in comparison to immature ones. Multivariate statistical analysis
      (principal component analysis, PCA, and agglomerative hierarchical clustering,
      AHC) was performed in order to verify the possibility of discrimination between
      immature and mature coffee samples. A clear separation between immature and
      mature coffees was observed based on AHC and PCA analyses of the normalized
      spectra obtained by employing both ATR and DR accessories. Linear discriminant
      analysis was employed for developing classification models, with recognition and
      prediction abilities of 100%. Such results showed that FTIR analysis presents
      potential for the development of a simple routine methodology for separation of
      immature and mature coffee beans. Practical Application: The ultimate goal of
      this research is to be able to propose improvements in the way immature coffee
      beans are separated from graded mature beans in coffee facilities (cooperatives
      and other coffee producer's associations). The results obtained herein point
      toward FTIR as a potential tool for the aimed improvements.

PMID- 22417581
TI  - Effect of cofermentation of grape varieties on aroma profiles of la mancha red
      wines.
AB  - The effect of winemaking using blends of red grape varieties cultivated in La
      Mancha region (Spain) on the aroma profile of wines was researched by chemical
      characterization. Free and glycosidically bound aroma compounds were isolated by
      solid phase extraction using dichloromethane and ethyl acetate, respectively, as
      solvents in elution and then analyzed by gas chromatography-mass spectrometry.
      Free and bound volatile compounds were analyzed in Cencibel, Bobal, and Moravia
      Agria monovarietal wines, and in 3 wines obtained with the blending of grapes:
      Cencibel (50%) + Bobal (50%); Cencibel (50%) + Moravia Agria (50%); Cencibel
      (33%) + Bobal (33%) + Moravia Agria (33%). Aroma compounds were studied in terms
      of odor activity values (OAVs). Ninety free aroma compounds and sixty-five bound
      aroma compounds were identified and quantified. The odor activity values for the
      different compounds were classified into 7 odorant series. The fruity and sweet
      series contributed most strongly to the aroma profile of all wines, independently
      of the winemaking technique used. In general, co-winemaking wines present a more
      complex chemical profile than monovarietal wines. Practical Application: Some
      grape varieties could benefit from this process with the presence of other
      varieties that might have an excess of aroma compounds. In this study, the wines
      were elaborated by blending different grape varieties together; this process
      implies co-maceration and co-fermentation steps. The co-winemaking technique
      could benefit from additional molecules provided by the other varieties, which
      results in a more complex formation than in the case of monovarietal wines. This
      technique provides a viable alternative to traditional winemaking methods for
      improving and enhancing the sensory profile of elaborated wines.

PMID- 22417582
TI  - Phenolic composition in different genotypes of Guabiju fruits (Myrcianthes
      pungens) and their potential as antioxidant and antichemotactic agents.
AB  - Fruits of Myrcianthes pungens Berg. Legr. (Myrtaceae), known as guabiju, are
      widely consumed fresh as well as dried, processed into jam, marmalade, and
      juices. In this study, chemical composition and antichemotactic and antioxidant
      activities of fruits from a wild type (GB) and 2 genotypes, PL2 and PL1, of
      guabiju were investigated. Total anthocyanins for the genotypes ranged from 334
      to 531 mg/100 g dry weight (dwt). Total flavonoids and polyphenols ranged from
      79.8 to 154 mg/100 g and 2438 to 4613 mg/100 g (dwt), respectively. A reversed
      phase liquid chromatography method with photodiode array detection was used to
      determine chemical profiles of the main anthocyanins found in the extracts. An
      HPLC method for the quantification of flavonoids is proposed, providing a simple
      procedure with rapid sample preparation. All samples contained 5 identical
      anthocyanidins, distributed differently, with cyanidin as the main compound.
      Identified flavonoids were quercitrin, hyperoside, and isoquercitrin; their
      relative amounts varied among the extracts. The antioxidant activity of guabiju
      methanolic extract was comparable to that of Trolox, and at a test concentration
      of 0.25 mg/mL, GB and PL2 activities were higher than those exhibited by Trolox.
      Total dry extracts of guabiju exhibited greater inhibition of chemotaxis at a
      concentration of 4 MUg/mL, except for GBH (wild-type hydrolyzed extract) which
      already presented high values at a concentration of 2 MUg/mL. These results
      suggest that the consumption of this fruit, rich in polyphenols, may be
      beneficial to human health. Practical Application: The paper is the first attempt
      on the improvement of this native fruit, since it is widely consumed regularly as
      part of the South American diet. The content of phenolic compounds demonstrates
      that consumption of guabiju would be beneficial to human health. Differences
      among samples, originating from open pollination of plants growing on the same
      site, lead to the conclusion that improvements can be made in the chemical
      composition and beneficial activity of guabiju fruits by simply selecting
      genotypes for these characteristics among open-pollinated seedlings.

PMID- 22417583
TI  - Comparison of the flavor chemistry and flavor stability of mozzarella and cheddar
      wheys.
AB  - The flavor and flavor stability of fresh and stored liquid Cheddar and Mozzarella
      wheys were compared. Pasteurized, fat separated, and unseparated Cheddar and
      Mozzarella wheys were manufactured in triplicate and evaluated immediately or
      stored for 72 h at 3  degrees C. Flavor profiles were documented by descriptive
      sensory analysis, and volatile components were extracted and characterized by
      solvent extraction followed by gas chromatography-mass spectrometry and gas
      chromatography-olfactometry with aroma extract dilution analysis. Cheddar and
      Mozzarella wheys were distinct by sensory and volatile analysis (P < 0.05). Fresh
      Cheddar whey had higher intensities of buttery and sweet aromatic flavors and
      higher cardboard flavor intensities following storage compared to Mozzarella
      whey. High aroma impact compounds (FD(log3)  > 8) in fresh Cheddar whey included
      diacetyl, 1-octen-3-one, 2-phenethanol, butyric acid, and (E)-2-nonenal, while
      those in Mozzarella whey included diacetyl, octanal, (E)-2-nonenal, and 2
      phenethanol. Fresh Cheddar whey had higher concentrations of diacetyl, 2/3-methyl
      butanal, (E)-2-nonenal, 2-phenethanol, and 1-octen-3-one compared to fresh
      Mozzarella whey. Lipid oxidation products increased in both whey types during
      storage but increases were more pronounced in Cheddar whey than Mozzarella whey.
      Increases in lipid oxidation products were also more pronounced in wheys without
      fat separation compared to those with fat separation. Results suggest that
      similar compounds in different concentrations comprise the flavor of these 2 whey
      sources and that steps should be taken to minimize lipid oxidation during fluid
      whey processing. Practical Application:  Cheddar and Mozzarella wheys are the
      primary sources of dried whey ingredients in the United States. An enhanced
      understanding of the flavor of these 2 raw product streams will enable
      manufacturers to identify methods to optimize quality.

PMID- 22417584
TI  - A profile of bioactive compounds of Rumex vesicarius L.
AB  - The present study was designed to investigate the bioactive compounds in extracts
      of Rumex vesicarius L. (Polygonaceae), a wild edible herb growing in Egypt. Ethyl
      acetate and n-butanol fractions of leaves of R. vesicarius were conducted by HPLC
      PDA-MS/MS-ESI in the negative mode to analyze phenolics content. Results revealed
      the identification of 13 phenolic compounds: 8-C-glucosyl-apigenin, 8-C-glucosyl
      luteolin, 6-C-hexosyl-quercetin, 3-O-rutinosyl-quercetin, 7-O-rhamno-hexosyl
      diosmetin, 7-O-rhamno-acetylhexosyl-diosmetin, catechin, epicatechin,
      ferulohexoside, 6-C-glucosyl-naringenin, epicatechin gallate, 6-C-glucosyl
      catechin, and epigallocatechin gallate. Quantification of the identified
      compounds revealed that 6-C-glucosyl-naringenin was the major compound. Also,
      qualitative and quantitative analysis of the hydro-ethanolic extract of leaves
      was carried out for ascorbic acid, alpha-tocopherol, beta-carotene. The essential
      oil as well as lipids analysis of saponifiable and unsaponifiable matters. The
      biochemical studies were conducted to evaluate the antioxidant and
      hepatoprotective potential of roots (REE), leaves (LEE), and fruits (FEE)
      ethanolic extracts of R. vesicarius (100 mg/kg b.wt., p.o., each) against
      hepatotoxicity induced by CCl(4)  (0.5 mL/kg b.wt., p.o., 3 times a week)
      compared with silymarin (50 mg/kg b.wt., p.o.) as standard drug. The results
      confirmed that coadministration of the tested extracts or silymarin with CCl(4) 
      for 4 wk exhibited a marked hepatoprotective activity, attributed to their
      antioxidant potential, membrane stabilizing effect, and antifibrogenic
      activities. Practical Application:  Investigation of the effect of hommad as a
      safe hepatoprotective diet that prospectively directs the attention to a valuable
      therapeutic natural herb rich in bioactive constituents.

PMID- 22417585
TI  - Survey of 1,2-dicarbonyl compounds in commercial honey of different floral
      origin.
AB  - In this study we conducted a survey of the concentrations of the major 1,2
      dicarbonyl compounds in 40 commercial honey samples from 12 different floral
      origins. 3-Deoxyglucosone (3-DG), glyoxal (GO), and methylglyoxal (MGO) were
      measured, using their corresponding quinoxaline derivatives, by high-performance
      liquid chromatography (HPLC). The analytical performance of the HPLC method for
      the analysis of 1,2-dicarbonyl compounds was evaluated in terms of linearity,
      limits of detection (LODs), limits of quantification (LOQs), and precision.
      Linearity over 2 orders of magnitude, LODs (0.01-0.04 mg/kg), and LOQs (0.03-0.12
      mg/kg) were calculated. Instrumental precision, as measured by the repeatability
      relative standard deviation% (RSDr%), was found to be between 0.22% and 0.55%.
      Furthermore, the concentrations of factors GO and MGO with respect to 3-DG were
      also calculated for rapid quantification in honey. In honey samples, the
      concentrations of 3-DG ranged from 75.9 to 808.6 mg/kg and were significantly
      higher (up to 100-fold) than those of 5-hydroxymethylfurfural (HMF). Values for
      GO and MGO were 0.1-10.9 and 0.2-2.9 mg/kg, respectively. The chemical
      characteristics that most influenced the levels of 1,2-dicarbonyl compounds in
      honey were found to be pH and total phenols. This was supported by multivariate
      analysis used to classify different honey types with respect to their chemical
      characteristics. In addition, both dicarbonyls and phenols are believed to
      contribute to the development of the final color of honey.

PMID- 22417586
TI  - State of dispersed lipid carrier and interface composition as determinants of
      beta-carotene stability in oil-in-water emulsions.
AB  - Liposoluble bioactive compounds are often included in foods in emulsified lipid
      carriers. In the present study, the impact of the physical state of the lipid
      carrier and the interfacial composition of oil-in-water emulsions on the
      stability of beta-carotene was studied. Emulsions with hydrogenated palm kernel
      oil (HPKO) concentration of 10% (w/w) dispersing 0.05% (w/w) beta-carotene, and a
      water phase at pH 7 containing 30% (w/w) sucrose, were stabilized by 1%, 1.5%,
      2%, and 3% (w/w) whey protein isolate (WPI). Crystallization and melting behavior
      of emulsified and bulk HPKO were studied by differential scanning calorimetry.
      The hysteresis of emulsified HPKO crystallization (onset approximately 10 
      degrees C; endset approximately 6  degrees C) and melting (onset approximately 17
      degrees C; endset approximately 45  degrees C) allowed us to operate at 15 
      degrees C on systems with identical compositions but different physical states of
      the same lipid phase. Surface protein coverage of emulsions was calculated and
      size of the dispersed particles was characterized by dynamic light scattering.
      beta-Carotene contents of the emulsions during storage at 15  degrees C was
      analyzed spectrophotometerically. Results highlighted an impact of the phase of
      the lipid carrier and of the concentration of WPI on beta-carotene degradation.
      beta-Carotene loss showed zero-order kinetics. A liquid dispersed phase resulted
      in a low degradation rate but a high concentration of protein on a solid lipid
      carrier was likewise effective for beta-carotene protection. Practical
      Application:  The inclusion of lipophilic bioactive compounds, such as
      carotenoids, is a current trend in the production of functional foods aiming to
      enhance health and well-being. However, the use of functional ingredients in food
      products is complicated because of the sensitivity of the active molecules to
      physical and chemical factors to which they are exposed during processing,
      storage, and consumption. The present work gives indications of the influence of
      the lipid carrier physical state and surface structure on beta-carotene stability
      in formulated oil-in-water liquid food models, suggesting possible strategies for
      an enhanced stabilization of lipophilic labile compounds.

PMID- 22417587
TI  - Jet-cooked high amylose corn starch and shortening composites for use in cake
      icings.
AB  - Butter cream is an all-purpose icing that is used to both ice and decorate cakes.
      Cream icings contain up to 40% shortening. As consumers become aware of the need
      to reduce fat in their diet, the demand for healthy, flavorful, and low-fat food
      increases. High-amylose corn starch was cooked in an excess-steam jet cooker in
      the presence of oleic acid. Amylose formed helical inclusion complexes with the
      fatty acid. Shortening was added at different levels to jet-cooked starch. The
      resulting starch-lipid composites (SLC) had 0%, 8%, 16%, and 24% fat. The
      composites were used to substitute shortening in the preparation of cake icings
      with 1% to 13% fat. SLC icings were formulated by either keeping the total solids
      constant, or the starch and sugar to water ratio constant as the fat level was
      reduced. The effect of fat and formulation of shortening and SLC icings on the
      physical and rheological characteristics were studied. It was found that low-fat
      SLC icings can be prepared by optimizing the formulation. Practical Application: 
      This study indicates potential new applications for SLC that benefit the
      confectionary industry by generating new products offering healthy alternatives
      to the consumers.

PMID- 22417588
TI  - Minimization of thermal impact by application of electrode cooling in a co-linear
      PEF treatment chamber.
AB  - A co-linear pulsed electric field (PEF) treatment chamber was analyzed and
      optimized considering electrical process conditions, temperature, and retention
      of heat-sensitive compounds during a continuous PEF treatment of peach juice. The
      applicability of a jacket heat-exchanger device surrounding the ground electrode
      was studied in order to provide active cooling and to avoid temperature peaks
      within the treatment chamber thus reducing the total thermal load to which the
      product is exposed. Simulation of the PEF process was performed using a finite
      element method prior to experimental verification. Inactivation of
      polyphenoloxydase (PPO) and peroxidase (POD) as well as the degradation of
      ascorbic acid (AA) in peach juice was quantified and used as indirect indicators
      for the temperature distribution. Peaks of product temperature within the
      treatment chamber were reduced, that is, from 98 to 75  degrees C and retention
      of the indicators PPO, POD, and AA increased by more than 10% after application
      of the active electrode cooling device. Practical Application:  The co-linear PEF
      treatment chamber is widely used for continuous PEF treatment of liquid products
      and also suitable for industrial scale application; however, Joule heating in
      combination with nonuniform electric field distribution may lead to unwanted
      thermal effects. The proposed design showed potential to reduce the thermal load,
      to which the food is exposed, allowing the retention of heat-sensitive
      components. The design is applicable at laboratory or industrial scale to perform
      PEF trials avoiding temperature peaks, which is also the basis for obtaining
      inactivation kinetic models with minimized thermal impact on the kinetic
      variables.

PMID- 22417589
TI  - Effect of temperature on microbial growth rate-mathematical analysis: the
      Arrhenius and Eyring-Polanyi connections.
AB  - The objective of this work is to develop a mathematical model for evaluating the
      effect of temperature on the rate of microbial growth. The new mathematical model
      is derived by combination and modification of the Arrhenius equation and the
      Eyring-Polanyi transition theory. The new model, suitable for both suboptimal and
      the entire growth temperature ranges, was validated using a collection of 23
      selected temperature-growth rate curves belonging to 5 groups of microorganisms,
      including Pseudomonas spp., Listeria monocytogenes, Salmonella spp., Clostridium
      perfringens, and Escherichia coli, from the published literature. The curve
      fitting is accomplished by nonlinear regression using the Levenberg-Marquardt
      algorithm. The resulting estimated growth rate (MU) values are highly correlated
      to the data collected from the literature (R(2) = 0.985, slope = 1.0, intercept =
      0.0). The bias factor (B(f) ) of the new model is very close to 1.0, while the
      accuracy factor (A(f) ) ranges from 1.0 to 1.22 for most data sets. The new model
      is compared favorably with the Ratkowsky square root model and the Eyring
      equation. Even with more parameters, the Akaike information criterion, Bayesian
      information criterion, and mean square errors of the new model are not
      statistically different from the square root model and the Eyring equation,
      suggesting that the model can be used to describe the inherent relationship
      between temperature and microbial growth rates. The results of this work show
      that the new growth rate model is suitable for describing the effect of
      temperature on microbial growth rate. Practical Application:  Temperature is one
      of the most significant factors affecting the growth of microorganisms in foods.
      This study attempts to develop and validate a mathematical model to describe the
      temperature dependence of microbial growth rate. The findings show that the new
      model is accurate and can be used to describe the effect of temperature on
      microbial growth rate in foods.

PMID- 22417590
TI  - In vitro and in vivo antihyperglycemic effect of 2 amadori rearrangement
      compounds, arginyl-fructose and arginyl-fructosyl-glucose.
AB  - During the heat processing of raw ginseng to produce red ginseng, amino acid
      derivatives such as arginyl-fructose (AF) and arginyl-fructosyl-glucose (AFG) are
      formed at high levels, through amadori rearrangement, the early step of Maillard
      reaction, from arginine and glucose or maltose, respectively. However, very
      limited information is available about the effect of the structural difference
      between AF and AFG on various biological activities. This is the first report of
      the mode of action and effect of AF and AFG on the type 2 diabetes management
      related inhibition of postprandial hyperglycemia in vitro and in animal model. In
      our previous study, standards AF and AFG were chemically synthesized and in this
      study their inhibitory activities against rat intestinal alpha-glucosidases and
      porcine pancreatic alpha-amylase were investigated in vitro. The IC(50)  value of
      the in vitro inhibitory activity of AF and AFG on rat intestinal sucrase was high
      and in similar levels (6.40 and 6.20 mM, respectively). Additionally, a mild
      pancreatic alpha-amylase inhibitory activity was observed, with IC(50)  values
      36.30 and 37.60 mM for AF and AFG, respectively. The effect of AF and AFG on the
      postprandial blood glucose increase after meal was investigated in Sprague Dawley
      rats fed on starch or sucrose meals. Both amadori compounds significantly reduced
      the postprandial blood glucose levels after starch or sucrose loading. These
      results indicate that AF and AFG, Maillard reaction products, may have
      antidiabetic effect by suppressing carbohydrate absorption in the
      gastrointestinal level, and thereby reducing the postprandial increase of blood
      glucose.

PMID- 22417591
TI  - Simultaneous enhancement of free isoflavone content and antioxidant potential of
      soybean by fermentation with Aspergillus oryzae.
AB  - In order to determine the fungal strain and fermentation period which produce the
      highest antioxidant activity of fermented soy product, soybean was fermented with
      Aspergillus oryzae NL 5 isolated from Korean traditional meju produced in
      Sunchang Yeastopia Land in Korea, and was subjected to analyzing isoflavone
      profiles and assaying antioxidant activity. Antioxidant potential of the samples
      was evaluated by ferric reducing antioxidant power assay, 2,2'-azinobis (2
      ethylbenzthiazoline-6-sulfonic acid) radical scavenging activity and total
      phenolic contents. In addition, antioxidant assay using fluorescent probes, 2',7'
      dichlorofluorescin diacetate and dihydroethidium, in HepG2 cells was conducted
      for the samples. The results showed that both high isoflavone variety Aga 3 and
      medium isoflavone variety Daewon of soybean fermented with Asp oryzae NL5 for 4
      to 5 d showed the highest increase in free isoflavone contents, together with the
      highest antioxidant activity. In conclusion, the antioxidant activity of
      fermented soy was proportional to the concentration of free isoflavones, and was
      significantly influenced by total isoflavone content of soybean variety and
      fermentation period. Practical Application:  Isoflavone profile and antioxidant
      capacity of soybean were widely variable during fermentation with Asp oryzae, and
      thereby it is recommended that meju (or koji) preparation condition, in
      particular, fermentation time is carefully optimized to maximize the antioxidant
      capacity of soy products fermented by Asp oryzae.

PMID- 22417592
TI  - Antihypertensive mechanism of a peptide-enriched soy sauce-like seasoning: the
      active constituents and its suppressive effect on renin-angiotensin-aldosterone
      system.
AB  - We previously reported that a peptide-enriched soy sauce-like seasoning called
      fermented soybean seasoning (FSS) demonstrated antihypertensive effects both in
      spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats. Angiotensin I
      converting enzyme (ACE) inhibitory substances (9 kinds of dipeptides and a
      nicotianamine) were identified from FSS. In the present study, we clarified the
      mechanisms underlying the antihypertensive effects of FSS in SHR. FSS was divided
      into the nicotianamine fraction and the peptide fraction. The peptide fraction
      was found to exert a more prevalent antihypertensive effect than the
      nicotianamine fraction in SHR. Among the peptides, we identified Gly-Tyr and Ser
      Tyr as the 2 primary substances in FSS that contributed to the antihypertensive
      effect in SHR. These peptides were neither degraded by acid nor gastrointestinal
      proteases, and were absorbed into the circulating blood. FSS (2000 mg/kg) exerted
      ACE inhibitory activity in the lung of rats and provided a decrease (P= 0.0067)
      in the level of serum aldosterone after a single oral administration in SHR,
      resulting in the antihypertensive effect. The antihypertensive mechanism was
      found to be similar to therapeutic ACE inhibitors and other food-derived ACE
      inhibitory peptides, which are in wide use and are recognized as safe.

PMID- 22417593
TI  - Antimicrobial activity of natural agents coated on starch-based films against
      Staphylococcus aureus.
AB  - This study investigated the antimicrobial (AM) activity of starch-based films
      coated with linalool, carvacrol, or thymol against Staphylococcus aureus in vitro
      or inoculated on the surface of Cheddar cheese. In solid media using the agar
      diffusion method, the inhibitory effect of linalool, carvacrol, or thymol coated
      onto the films increased significantly (P<= 0.05) with the increase in
      concentration of each AM agent. All the coated films effectively inhibited the
      growth of S. aureus on the surface of Cheddar cheese. The sensitivity of S.
      aureus to the AM agents tested in the concentration range of the study is in the
      order of thymol > carvacrol > linalool.

PMID- 22417594
TI  - Inhibitory effects of various essential oils and individual components against
      extended-spectrum beta-lactamase (ESBL) produced by Klebsiella pneumoniae and
      their chemical compositions.
AB  - In the current study, in vitro inhibitory activity of several essential oils
      obtained from the cultivated plants, Foeniculum vulgare, Mentha piperita and M.
      spicata, Ocimum basilicum, Origanum majorana, O. onites, O. vulgare, Satureja
      cuneifolia, and a number of individual essential oil components of terpene and
      aromatic types were screened against 10 isolated strains of Klebsiella pneumoniae
      producing extended-spectrum beta-lactamase (ESBL) enzyme, which makes this
      microorganism quite resistant against the antibiotics: trimetoprime
      sulfametoksazol, sulbactam-ampicilin, clavulonate-amoxicilin, ceftriaxon,
      cefepime, imipenem, ceftazidime, tobramicine, gentamisine, ofloxacin, and
      ciprofloksasin. All of the essential oils and the components exerted a remarkable
      inhibition ranging between 32 and 64 MUg/mL against all of these strains as
      strong as the references (ampicilin and oflaxocin) inhibiting at 32 MUg/mL.
      Besides, chemical compositions of the essential oils were elucidated by gas
      chromatography-mass spectrometry (GC-MS). The essential oils and the pure
      components widely found in essential oils screened herein have shown remarkable
      inhibition against ESBL-producing K. pneumoniae strains, which leads to the
      suggestion that they may be used as food preservatives for this purpose.
      Practical Application:  The essential oils obtained from Foeniculum vulgare,
      Mentha piperita and M. spicata, O.cimum basilicum, Origanum majorana, O. onites,
      O. vulgare, and Satureja cuneifolia as well as common essential oil components
      have shown notable inhibitory effects against 10 isolated strains of Klebsiella
      pneumoniae producing extended-spectrum beta-lactamase (ESBL) enzyme and they
      might be used as food preservative or ingredient.

PMID- 22417595
TI  - Evaluating the effect of temperature on microbial growth rate--the Ratkowsky and
      a Belehradek-type models.
AB  - The objective of this paper to conduct a parallel comparison of a new Belehradek
      type growth rate (with an exponent of 1.5, or the Huang model), Ratkowsky square
      root, and Ratkowsky square equations as secondary models for evaluating the
      effect of temperature on the growth of microorganisms. Growth rates of
      psychrotrophs and mesophiles were selected from the literature, and independently
      analyzed with the 3 models using nonlinear regression. Analysis of variance
      (ANOVA) was used to compare the means of growth rate (MU), estimated minimum
      temperature (T(min) ), approximate standard errors (SE) of T(min) , model mean
      square errors (MSE), accuracy factor (A(f) ), bias factor (B(f) ), relative
      residual errors (delta), Akaike information criterion (AICc), and Bayesian
      information criterion (BIC). Based on the estimated T(min)  values, the Huang
      model distinctively classified the bacteria into 2 groups (psychrotrophs and
      mesophiles). No significant difference (P > 0.05) was observed among the means of
      the MU values reported in the literature or estimated by the 3 models, suggesting
      that all 3 models were suitable for curve fitting. Nor was there any significant
      difference in MSE, SE, delta, A(f) , B(f) , AICc, and BIC. The T(min)  values
      estimated by the Huang model were significantly higher than those estimated by
      the Ratkowsky models, but were in closer agreement with the biological minimum
      temperatures for both psychrotrophs and mesophiles. The T(min)  values estimated
      by the Ratkowsky models systematically underestimated the minimum growth
      temperatures. In addition, statistical estimation showed that the mean exponent
      for the new Belehradek-type growth rate model may indeed be 1.5, further
      supporting the validity of the Huang model.

PMID- 22417596
TI  - The olive compound 4-hydroxytyrosol inactivates Staphylococcus aureus bacteria
      and Staphylococcal Enterotoxin A (SEA).
AB  - The foodborne pathogen Staphylococcus aureus produces the virulent staphylococcal
      enterotoxin A (SEA), a single chain protein which consists of 233 amino acid
      residues with a molecular weight of 27078 Da. SEA is a superantigen that is
      reported to contribute to animal (mastitis) and human (emesis, diarrhea, atopic
      dermatitis, arthritis, and toxic shock) syndromes. Changes in the native
      structural integrity may inactivate the toxin by preventing molecular interaction
      with cell membrane receptor sites of their host cells. In the present study, we
      evaluated the ability of the pure olive compound 4-hydroxytyrosol and a
      commercial olive powder called Hidrox-12, prepared by freeze-drying olive juice,
      to inhibit S. aureus bacteria and SEA's biological activity. Dilutions of both
      test substances inactivated the pathogens. Two independent cell assays (BrdU
      incorporation into newly synthesized DNA and glycyl-phenylalanyl
      aminofluorocoumarin proteolysis) demonstrated that the olive compound 4
      hydroxytyrosol also inactivated the biological activity of SEA at concentrations
      that were not toxic to the spleen cells. However, efforts to determine inhibition
      of the toxin by Hidrox-12 were not successful because the olive powder was
      cytotoxic to the spleen cells at concentrations found to be effective against the
      bacteria. The results suggest that food-compatible and safe antitoxin olive
      compounds can be used to inactivate both pathogens and toxins produced by the
      pathogens. Practical Application:  The results of this study suggest that food
      compatible and safe antitoxin olive compounds can be used to reduce both
      pathogens and toxins produced by the pathogens in foods.

PMID- 22417597
TI  - Quantification of Salmonella in food samples from India using the MINI-MSRV MPN
      and modified MINI-MSRV MPN methods.
AB  - Salmonella is one of the most important food-borne pathogens. The MINI-MSRV MPN
      method was modified by replacing the isolation and confirmation of Salmonella on
      selective chromogenic agar with PCR/RT-PCR. This modification reduced the time
      for quantification by the MINI-MSRV MPN method by 24 h. Ninety-seven different
      food samples, comprising chicken, mutton, fish, and sprouts from different
      markets in Mumbai, India, were analyzed for quantification of Salmonella species
      by the MINI-MSRV MPN and modified MINI-MSRV MPN methods. Seventy-four percent of
      the chicken samples were found positive for Salmonella. However, Salmonella was
      found to be absent in fish, mutton, and sprouts samples. Salmonella load in the
      chicken sample was in the range of 1.30 to 120 MPN/g. This genotypic confirmation
      has advantage over variable phenotypic confirmation of pathogens.

PMID- 22417598
TI  - Rapid and accurate bacterial identification in probiotics and yoghurts by MALDI
      TOF mass spectrometry.
AB  - Probiotic food is manufactured by adding probiotic strains simultaneously with
      starter cultures in fermentation tanks. Here, we investigate the accuracy and
      feasibility of matrix-assisted laser desorption/ionisation time-of-flight mass
      spectrometry (MALDI-TOF MS) for bacterial identification at the species level in
      probiotic food and yoghurts. Probiotic food and yoghurts were cultured in
      Columbia and Lactobacillus specific agar and tested by quantitative real-time PCR
      (qPCR) for the detection and quantification of Lactobacillus sp. Bacterial
      identification was performed by MALDI-TOF analysis and by amplification and
      sequencing of tuf and 16S rDNA genes. We tested 13 probiotic food and yoghurts
      and we identified by qPCR that they presented 10(6)  to 10(7)  copies of
      Lactobacillus spp. DNA/g. All products contained very large numbers of living
      bacteria varying from 10(6)  to 10(9)  colony forming units/g. These bacteria
      were identified as Lactobacillus casei, Lactococcus lactis, Bifidobacterium
      animalis, Lactobacillus delbrueckii, and Streptococcus thermophilus. MALDI-TOF MS
      presented 92% specificity compared to the molecular assays. In one product we
      found L. lactis, instead of Bifidus spp. which was mentioned on the label and for
      another L. delbrueckii and S. thermophilus instead of Bifidus spp. MALDI-TOF MS
      allows a rapid and accurate bacterial identification at the species level in
      probiotic food and yoghurts. Although the safety and functionality of probiotics
      are species and strain dependent, we found a discrepancy between the bacterial
      strain announced on the label and the strain identified. Practical Application: 
      MALDI-TOF MS is rapid and specific for the identification of bacteria in
      probiotic food and yoghurts. Although the safety and functionality of probiotics
      are species and strain dependent, we found a discrepancy between the bacterial
      strain announced on the label and the strain identified.

PMID- 22417599
TI  - Shelf life extension of sugarcane juice using preservatives and gamma radiation
      processing.
AB  - Preserving raw sugarcane juice is a challenging problem. Sugarcane juice turns
      brown soon after its extraction and gets spoiled due to fermentation within
      hours. A combination of gamma radiation (5 kGy) with permitted preservatives and
      low temperature storage (10  degrees C) could preserve raw sugarcane juice for
      more than a month. The preservatives used were citric acid (0.3%), sodium
      benzoate (0.015%), potassium sorbate (0.025%), and sucrose (10%). The treatment
      helped in extending the shelf life to 15 d at ambient temperature (26 +/- 2 
      degrees C) and 35 d at 10  degrees C. The microbial load was found to be below
      detectable limit within this period. The biochemicals like phenolics and
      flavonoids were not found to be affected by addition of these preservatives. The
      antioxidant activities including free radical scavenging activity, nitrite
      scavenging activity, and reducing power were also not significantly affected. The
      sensory evaluation scores showed that the juice with this combination treatment
      was highly acceptable.

PMID- 22417600
TI  - Preparation and properties of polypropylene/clay nanocomposites for food
      packaging.
AB  - Polypropylene (PP)/clay nanocomposites based on PP, organic clay
      (montmorillonite; MMT), and maleated polypropylene (MAPP) were prepared by melt
      compounding. The mechanical, thermal, morphological, and gas barrier properties
      of the resulting PP/clay nanocomposites were investigated at varying
      concentrations of the components for food packaging. The results revealed that
      the mechanical strengths, including tensile, flexural, and Izod impact strength,
      were increased for PP/clay nanocomposites compared to neat PP. The thermal
      properties showed a tendency for the melting and degradation temperatures to
      increase with the clay concentration. The effect of the compatibilizer was
      observed using scanning electron microscopy (SEM). The X-ray diffraction pattern
      of the nanocomposites revealed increased d-spacing of the MMT layers, indicating
      that the compatibility of neat PP and clay was improved by the addition of MAPP,
      and the intercalation and partial exfoliation of the layers. The use of clay
      increased the mobility distance of the gas molecules, leading to the oxygen
      permeability of neat PP being reduced by 26% to 55%.

PMID- 22417601
TI  - Water vapor adsorption isotherms of agar-based nanocomposite films.
AB  - Adsorption isotherms of agar and agar/clay nanocomposite films prepared with
      different types of nanoclays, that is, a natural montmorillonite (Cloisite Na(+)
      ) and 2 organically modified montmorillonites (Cloisite 30B and Cloisite 20A),
      were determined at 3 different temperatures (10, 25, and 40  degrees C). The
      water vapor adsorption behavior of the nanocomposite films was found to be
      greatly influenced with the type of clay. The Guggenheim-Anderson-de Boer (GAB)
      isotherm model parameters were estimated by using both polynomial regression and
      nonlinear regression methods and it was found that the GAB model fitted
      adequately for describing experimental adsorption isotherm data for the film
      samples. The monolayer moisture content (m(o) ) of the film samples was also
      greatly affected by the type of nanoclay used, that is, m(o)  of nanocomposite
      films was significantly lower than that of the neat agar film. Nanocomposite
      films prepared with hydrophobic nanoclays (Cloisite 30B and Cloisite 20A)
      exhibited lower m(o)  values than those prepared with hydrophilic nanoclay
      (Cloisite Na(+) ).

PMID- 22417602
TI  - Role of glassy state on stabilities of freeze-dried probiotics.
AB  - High viability of dried probiotics is of great importance for immediate recovery
      of activity in fermented foods and for health-promoting effects of
      nutraceuticals. The conventional process for the production of dried probiotics
      is freeze-drying. However, loss of viability occurs during the drying and storage
      of the dried powder. It is believed that achieving the "glassy state" is
      necessary for survival, and the glassy state should be retained during freezing,
      drying, and storage of cells. Insight into the role of glassy state has been
      largely adopted from studies conducted with proteins and foods. However, studies
      on the role of glassy state particularly with probiotic cells are on the
      increase, and both common and explicit findings have been reported. Current
      understanding of the role of the glassy state on viability of probiotics is not
      only valuable for the production of fermented foods and nutraceuticals but also
      for the development of nonfermented functional foods that use the dried powder as
      an adjunct. Therefore, the aim of this review is to bring together recent
      findings on the role of glassy state on survival of probiotics during each step
      of production and storage. The prevailing state of knowledge and recent finding
      are discussed. The major gaps of knowledge have been identified and the
      perspective of ongoing and future research is addressed.

PMID- 22417603
TI  - The black agonist-receptor model of high potency sweeteners, and its implication
      to sweetness taste and sweetener design.
AB  - The dose responses of the most commonly used high potency sweeteners (HPSs) have
      been measured by a more precise sensory procedure. The data were analyzed by
      Black's pharmacological model that takes into account not only agonist binding
      affinity but transduction efficiency as well. HPSs are clearly segregated into 2
      groups depending on whether they bind to T1R2 or T1R3 of the receptor
      heterodimer. Surprisingly, the more potent sweeteners have lower transduction
      efficiencies. The implications of these on consumer product development and HPS
      design are discussed.

PMID- 22417604
TI  - Consumer preferences and willingness to pay for value-added chicken product
      attributes.
AB  - A growing demand for convenient and ready-to-eat products has increased poultry
      processors' interest in developing consumer-oriented value-added chicken
      products. In this study, a conjoint analysis survey of 276 chicken consumers in
      Edmonton was conducted during the summer of 2009 to assess the importance of the
      chicken part, production method, processing method, storage method, the presence
      of added flavor, and cooking method on consumer preferences for different value
      added chicken product attributes. Estimates of consumer willingness to pay (WTP)
      premium prices for different combinations of value-added chicken attributes were
      also determined. Participants'"ideal" chicken product was a refrigerated product
      made with free-range chicken breast, produced with no additives or preservatives
      and no added flavor, which could be oven heated or pan heated. Half of all
      participants on average were willing to pay 30% more for a value-added chicken
      product over the price of a conventional product. Overall, young consumers,
      individuals who shop at Farmers' Markets and those who prefer free-range or
      organic products were more likely to pay a premium for value-added chicken
      products. As expected, consumers' WTP was affected negatively by product price.
      Combined knowledge of consumer product attribute preferences and consumer WTP for
      value-added chicken products can help the poultry industry design innovative
      value-added chicken products. Practical Application:  An optimum combination of
      product attributes desired by consumers for the development of a new value-added
      chicken product, as well as the WTP for this product, have been identified in
      this study. This information is relevant to the poultry industry to enhance
      consumer satisfaction of future value-added chicken products and provide the
      tools for future profit growth.

PMID- 22417605
TI  - Optimization of consumer acceptability and sensory characteristics for marinated
      broiler breast meat.
AB  - In the present study, the effects of marination on the quality of poultry breast
      meat deboned at various times postmortem (PM) were investigated. One of the
      specific goals was to optimize the processing conditions between deboning time,
      tumbling duration, and poultry breast meat tenderness, with the objective of
      developing specific recommendations on processing practices adopted by the
      poultry industry. Broiler breast (Pectoralis major) muscles deboned at 0.25, 1.5,
      3, 6, and 24 h PM were vacuum tumbled with 20% solution added containing 1% salt
      and 0.45% sodium tripolyphosphate for either 15 or 30 min. Meat quality
      measurements including marination uptake, retention, cooking loss, instrumental
      texture, sensory descriptive analysis, and consumer acceptance were performed.
      Results indicated that acceptable tenderness was achieved for marinated
      treatments deboned at 3 h or later PM. Fillets deboned at shorter PM were rated
      tough by consumers. Marination duration had very little effect on the quality of
      the meat processed. Practical Application:  For the poultry industry to maximize
      consumer acceptance for marinated broiler breast meat, this research will be of
      benefit. Various qualities of broiler breast meat such as tenderness and water
      holding capacities were examined under different marination conditions.

PMID- 22417606
TI  - Effect of 1-methylcyclopropene on chilling injury and quality of peach fruit
      during cold storage.
AB  - The effects of different concentrations (0, 0.1, 0.5, 1, and 5 MUL/L) of 1
      methylcyclopropene (1-MCP) on chilling injury (CI), fruit quality, and
      antioxidant enzyme activities in cold-stored peach fruit (Prunus persica Batsch
      cv Baifeng) were investigated. The results showed that treatment with 0.5 MUL/L 1
      MCP significantly alleviated CI symptoms, including internal browing (IB) and
      flesh mealiness (FM), and maintained higher fruit quality. In addition, 1-MCP
      inhibited the activities of polyphenol oxidase (PPO) and peroxidase (POD),
      maintained higher activities of antioxidant enzymes and kept the balance of the
      polygalacturonase (PG)/pectinmethylesterase (PME) ratio. The treatment of 1-MCP
      markedly inhibited the increase of electrolyte leakage and the accumulation of
      malondialdehyde and hydrogen peroxide. Thus, 1-MCP (0.5 MUL/L) treatment is
      effective in preventing CI and maintaining overall quality in peach fruit. The
      effect of 1-MCP on alleviating CI may be due to its capability to enhance
      antioxidant enzyme activities and to reduce oxidative damage. Practical
      Application:  Treatment with 0.5 MUL/L 1-MCP significantly prevented chilling
      injury and maintained fruit quality in "Baifeng" peaches. In addition, 1-MCP
      could enhance antioxidant enzyme activities and alleviate oxidative damage. Thus,
      1-MCP has the potential for application in the Asiatic peach industry.

PMID- 22417607
TI  - The effectiveness of ozone and acidulant treatments in extending the refrigerated
      shelf life of fresh-cut potatoes.
AB  - The objective of the study was to determine the effectiveness of acidulant dip
      treatments (with or without aqueous ozone) to reduce enzymatic browning and to
      extend the shelf life of fresh-cut potato slices during refrigerated storage (4 
      degrees C) for 28 d. Potato slices subjected to aqueous ozone (2 ppm) had
      significantly (P<= 0.05) higher L-values and lower a-values, but ozone did not
      appear to have any effect on aerobic plate counts (APCs) or polyphenol oxidase
      (PPO) activity. NatureSeal (NS) and sodium acid sulfate (SAS) were the most
      effective acidulant treatments in reducing browning (significantly [P<= 0.05]
      higher L-values, lower a-values, and browning index values) regardless of ozone
      treatment. NS and SAS also had lower PPO activity compared to other treatments on
      days 0 and 28, and significantly (P<= 0.05) lower APCs (<=2.00 log CFU/g) over
      refrigerated storage. Therefore, the SAS treatment was comparable to NS, a
      commercially available product, and showed promise as an effective antibrowning
      dip to reduce browning and spoilage in fresh-cut potato products. Practical
      Application:  A 1% SAS dip treatment which included 1% citric and 1% ascorbic
      acid was found to be an effective antibrowning dip for fresh-cut potatoes along
      with NatureSeal(r)'s PS-10, compared to other treatments. They were both
      effective in maintaining low microbial counts over refrigerated storage.
      Additionally, aqueous ozone washes (2 ppm) showed significant benefits to reduce
      browning; however, ozone did not affect microbial counts or PPO enzyme activity.
      Therefore, the SAS treatment could have potential use in the fruit and vegetable
      industry to reduce browning and spoilage in fresh-cut potato products.

PMID- 22417608
TI  - Wild buckwheat is unlikely to pose a risk to buckwheat-allergic individuals.
AB  - Buckwheat (Fagopyrum esculentum) is a commonly allergenic food especially in Asia
      where buckwheat is more commonly consumed. Wild buckwheat (Polygonum convolvulus,
      recently changed to Fallopia convolvulus) is an annual weed prevalent in grain
      growing areas of the United States. Wild buckwheat is not closely related to
      edible buckwheat although the seeds do have some physical resemblance. A large
      shipment of wheat into Japan was halted by the discovery of the adventitious
      presence of wild buckwheat seeds over possible concerns for buckwheat-allergic
      consumers. However, IgE-binding was not observed to an extract of wild buckwheat
      using sera from 3 buckwheat-allergic individuals either by radio-allergosorbent
      test inhibition or by immunoblotting after protein separation by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. Furthermore, the extract of wild
      buckwheat was not detected in a buckwheat enzyme-linked immunosorbent assay
      developed with antisera against common buckwheat. Thus, wild buckwheat is highly
      unlikely to pose any risk to buckwheat-allergic individuals. The common names of
      plants should not be a factor in the risk assessment for possible cross
      allergenicity.

PMID- 22417609
TI  - Effects of raspberry phytochemical extract on cell proliferation, apoptosis, and
      serum proteomics in a rat model.
AB  - The red raspberry extract possesses potent antioxidant capacity and anticancerous
      activity in vitro and in vivo. The objective of this study was to determine
      whether red raspberry extract affected the cell cycle, angiogenesis, and
      apoptosis in hepatic lesion tissues from a rat model induced by
      diethylnitrosamine (DEN) as well as changes of serum proteomics. Rats were
      treated with red raspberry extract (0.75, 1.5, or 3.0 g/kg of body weight) by
      gavage starting 2 h after DEN administration and continued for 20 wk. Red
      raspberry extract inhibited cell proliferation, vascular endothelial growth
      factor VEGF expression, and induced apoptosis in the hepatic lesion tissues. In
      addition, 2 protein peaks (2597.93 and 4513.88 m/z) were identified to
      differentially express in the 3.0 g/kg body weight and positive control groups by
      serum proteomics. These results suggest that a dietary supplement with red
      raspberry effectively protects against chemically induced hepatic lesions in
      rats.

PMID- 22417613
TI  - Development of a rapid method for the determination and confirmation of
      nitroimidazoles in six matrices by fast liquid chromatography-tandem mass
      spectrometry.
AB  - A rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was
      developed to identify and to quantify nitroimidazoles, metronidazole (MNZ),
      ronidazole (RNZ) and dimetridazole (DMZ) and their corresponding hydroxy
      metabolites, MNZ-OH and 2-hydroxymethyl-1-methyl-5-nitroimidazole (HMNNI) in
      plasma, milk, muscle, egg, honey and feed samples. The same sample clean-up
      procedure including a novel solid-phase extraction (SPE) on polymeric Strata-SDB
      cartridges was used for each matrix. The analytes were separated on Kinetex XB C
      18 core-shell type HPLC column using isocratic elution mode with a mobile phase
      containing 0.1% formic acid in water/methanol (88/12, v/v, pH 2.6) at a flow rate
      of 0.7 ml/min. The main advantage of the developed method is that the analysis
      time of only 3 min, which is about three to ten times shorter than in other
      reported HPLC methods. The developed method was validated using a matrix
      comprehensive in-house validation strategy. The matrix effect of LC-MS/MS
      analysis was also investigated. Results are presented from the successful
      application of the developed method to an incurred pork meat certified reference
      material and to incur porcine plasmas in a proficiency test in year 2011.

PMID- 22417614
TI  - Characterization and identification of baccharane glycosides in Impatientis Semen
      by rapid-resolution liquid chromatography with electrospray ionization quadrupole
      time-of-flight tandem mass spectrometry.
AB  - Baccharane glycosides represent a group of rare saponins in plant kingdom and
      have been regarded as chemical marker for quality control of Impatientis Semen.
      Based on the structural skeleton, the baccharane glycosides were classified into
      three types: hosenkol A, hosenkol B and hosenkol C type. In this study, a rapid
      resolution liquid chromatography coupled with electrospray ionization quadrupole
      time-of-flight tandem mass spectrometry (RRLC/ESI-Q-TOF MS/MS) was performed to
      investigate the fragmentation behaviours of baccharane glycosides from
      Impatientis Semen. In full scan mass spectrum, the accurate determination of
      molecular formula was obtained by the predominant ion [M+COO](-) in negative
      mode. In the MS/MS spectrum, fragmentation reactions of the [M+H](+) acquired in
      positive mode were recorded to provide abundant structural information on the
      aglycone and glycosyl moieties. The characteristic ion for hosenkol A and
      hosenkol B type glycosides was at m/z 399, while for hosenkol C type glycosides
      the diagnostic ion was at m/z 381. Neutral losses of monosaccharide,
      disaccharide, H(2)O and C(3)H(4) were observed for stepwise structural
      characterization. As a result, 19 compounds including 9 target saponins and 10
      non-target saponins were rapidly screened out in ethanol extract of Impatientis
      Semen, and 5 of them were found to be novel baccharane glycosides.

PMID- 22417615
TI  - Importance of retention data from affinity and reverse-phase high-performance
      liquid chromatography on antitumor activity prediction of imidazoacridinones
      using QSAR strategy.
AB  - Quantitative structure-activity relationships (QSAR) studies for prediction of
      cytotoxic and antitumor activity of imidazoacridinones (IA) based on
      experimentally obtained high-performance liquid chromatography (HPLC) retention
      data and calculated parameters using computational (molecular modeling) medicinal
      chemistry methods were proposed. The RP-HPLC and affinity-HPLC chromatographic
      techniques with four diversified HPLC systems applying columns with
      octadecylsilanes (C18), phosphatidylcholine (IAM), as well as alpha(1)
      glycoprotein (AGP) and albumin (HSA) were used for the determination of the
      retention constants logk and logk(w) which characterize lipophilicity and protein
      affinity of IA. Moreover, molecular modeling studies were performed using
      HyperChem and Dragon software's, and structural descriptors were calculated and
      subsequently used. The QSAR equations using multiple linear regression (MLR)
      analysis method were derived which indicated that in vivo antileukemia activity
      of IA depends on cytotoxic activity against leukemia cells, whereas this
      cytotoxic activity depends on logk and logk(w) parameters obtained on all HPLC
      systems. Moreover, the QSRR equations were derived and indicated that logk and
      logk(w) parameters depend on calculated non-empirical structural parameters. The
      predictive power of obtained QSAR and QSRR equations allowed the prediction of
      cytotoxic and antitumor activity of IA and also their HPLC retention parameters.
      Finally, the equations can be used for prediction of antileukemia activity of IA
      without the necessity of carrying out experimental measurements.

PMID- 22417616
TI  - Revisiting the genomes of the Staphylococcus aureus strains NCTC 8325 and RN4220.
AB  - Whole-genome sequence comparison of Staphylococcus aureus strain RN4220DeltamutS,
      a variant of strain RN4220 carrying an insertion in the mutS gene, and its parent
      strain S. aureus NCTC 8325 identified variations in the nucleic acid sequence
      between both strains. Some of these changes concerned proteins which are part of
      the ribosome (RpmF, RpsB), process ribosomal RNA (RimM), are involved in cell
      wall biosynthesis (EzrA, MurA), or possess chaperone functions (GroEL) and
      therefore might compromise the fitness of the affected strain. Resequencing of
      these genes in S. aureus NCTC 8325 revealed that the sequence variations
      represent errors in the original S. aureus NCTC 8325 genome sequence and do not
      constitute mutations in S. aureus RN4220 or RN4220DeltamutS. In correlation with
      these results, growth experiments showed that the fitness of S. aureus RN4220 is
      comparable to that of S. aureus NCTC 8325.

PMID- 22417617
TI  - Inducing healing-like human primary macrophage phenotypes by 3D hydrogel coated
      nanofibres.
AB  - Immune cells are present in the blood and in resident tissues, and the nature of
      their reaction towards biomaterials is decisive for materials success or failure.
      Macrophages may for example be classically activated to trigger inflammation
      (M1), or alternatively activated which supports healing and vascularisation (M2).
      Here, we have generated 3D nanofibrous meshes in different porosities and
      precisely controlled surface chemistries comprising PLGA, hydrogel-coated protein
      repellant and protein repellant endowed with the bioactive peptide sequences
      GRGDS or GLF. We also prepared 2D substrates with corresponding surface chemistry
      for a systematic evaluation of primary human macrophage adhesion, migration,
      transcriptome expression, cytokine release and surface marker expression. Our
      data show that material morphology is a powerful means in biomaterial design to
      influence immune cell response. Flat substrates lead to an increased number of M2
      classified CD163(+) macrophages. However, these M2 cells released large amounts
      of pro-inflammatory cytokines. In contrast, 3D nanofibres with corresponding
      surface chemistry yielded M1 classified 27E10(+) macrophages with a significantly
      increased release of pro-angiogenic chemokines and angiogenesis related molecules
      and a strong decrease of pro-inflammatory cytokines. We thus suggest that, for
      macrophages in contact with biomaterials, cytokine release is taken as main
      criterion instead of surface-markers for macrophage classifications.

PMID- 22417618
TI  - Integration of basal topographic cues and apical shear stress in vascular
      endothelial cells.
AB  - In vivo, vascular endothelial cells (VECs) are anchored to the underlying stroma
      through a specialization of the extracellular matrix, the basement membrane (BM)
      which provides a variety of substratum associated biophysical cues that have been
      shown to regulate fundamental VEC behaviors. VEC function and homeostasis are
      also influenced by hemodynamic cues applied to their apical surface. How the
      combination of these biophysical cues impacts fundamental VEC behavior remains
      poorly studied. In the present study, we investigated the impact of providing
      biophysical cues simultaneously to the basal and apical surfaces of human aortic
      endothelial cells (HAECs). Anisotropically ordered patterned surfaces of
      alternating ridges and grooves and isotropic holed surfaces of varying pitch
      (pitch = ridge or hole width + intervening groove or planar regions) were
      fabricated and seeded with HAECs. The cells were then subjected to a steady shear
      stress of 20 dyne/cm(2) applied either parallel or perpendicular to the direction
      of the ridge/groove topography. HAECs subjected to flow parallel to the
      ridge/groove topography exhibited protagonistic effects of the two stimuli on
      cellular orientation and elongation. In contrast, flow perpendicular to the
      substrate topography resulted in largely antagonistic effects. Interestingly, the
      behavior depended on the shape and size of the topographic features. HAECs
      exhibited a response that was less influenced by the substratum and primarily
      driven by flow on isotropically ordered holed surfaces of identical pitch to the
      anistropically ordered surfaces of alternating ridges and grooves. Simultaneous
      presentation of biophysical cues to the basal and apical aspects of cells also
      influenced nuclear orientation and elongation; however, the extent of nuclear
      realignment was more modest in comparison to cellular realignment regardless of
      the surface order of topographic features. Flow-induced HAEC migration was also
      influenced by the ridge/groove surface topographic features with significantly
      altered migration direction and increased migration tortuosity when flow was
      oriented perpendicular to the topography; this effect was also pitch-dependent.
      The present findings provide valuable insight into the interaction of
      biologically relevant apical and basal biophysical cues in regulating cellular
      behavior and promise to inform improved prosthetic design.

PMID- 22417619
TI  - Freeform fabricated scaffolds with roughened struts that enhance both stem cell
      proliferation and differentiation by controlling cell shape.
AB  - We demonstrate that freeform fabricated (FFF) scaffolds with a roughened surface
      topography can support hBMSC proliferation, while also inducing osteogenic
      differentiation, for maximized generation of calcified, bone-like tissue.
      Previously, hBMSCs rapidly proliferated, without osteogenic differentiation,
      during culture in FFF scaffolds. In contrast, hBMSCs underwent osteogenic
      differentiation, with slow proliferation, during culture in nanofiber scaffolds.
      Analysis of cell morphology showed that the topography presented by the nanofiber
      scaffolds drove hBMSC differentiation by guiding them into a morphology that
      induced osteogenic differentiation. Herein, we hypothesized that using the high
      surface area architecture of FFF scaffolds to present a surface roughness that
      drives hBMSCs into a morphology that induces osteogenic differentiation would
      yield a maximum amount differentiated hBMSCs and bone-like tissue. Thus, a
      solvent etching method was developed that imparted a 5-fold increase in roughness
      to the surface of the struts of poly(epsilon-caprolactone) (PCL) FFF scaffolds.
      The etched scaffolds induced osteogenic differentiation of the hBMSCs while un
      etched scaffolds did not. The etched scaffolds also supported the same high
      levels of hBMSC proliferation that un-etched scaffolds supported. Finally, hBMSCs
      on un-etched scaffolds had a large spread area, while hBMSCs on etched scaffolds
      has a smaller area and were more rounded, indicating that the surface roughness
      from the etched scaffolds dictated the morphology of the hBMSCs. The results
      demonstrate that FFF scaffolds with surface roughness can support hBMSC
      proliferation, while also inducing osteogenic differentiation, to maximize
      generation of calcified tissue. This work validates a rational approach to
      scaffold fabrication where the structure of the scaffold was designed to optimize
      stem cell function by controlling cell morphology.

PMID- 22417621
TI  - Depolymerized chitosans functionalized with bPEI as carriers of nucleic acids and
      tuftsin-tethered conjugate for macrophage targeting.
AB  - Development of efficient and safe nucleic acid carriers (vectors) is one of the
      essential requirements for the success of gene therapy. Here, we have evaluated
      the gene transfer capability of chitosan-PEI (CP) conjugates prepared by
      conjugating low molecular weight branched polyethylenimine (LMWP) with
      depolymerized chitosans (7 and 10 kDa) via their terminal aldehyde/keto groups.
      The CP conjugates interacted efficiently with nucleic acids and also showed
      higher cellular uptake. These conjugates on complexation with DNA yielded
      nanoparticles in the size range of 100-130 nm (in case of C7P) and 115-160 nm (in
      case of C10P), which exhibited significantly higher transfection efficiency (~2
      42 folds) in vitro compared to chitosans (high and low mol. wt.) and the
      commercially available transfection reagents retaining cell viability almost
      comparable to the native chitosan. Of the two CP conjugates, chitosan 7 kDa-LMWP
      (C7P) displayed higher gene transfer ability in the presence and absence of
      serum. Luciferase reporter gene analysis in male Balb/c mice receiving
      intravenous administration of C7P3/DNA polyplex showed the maximum expression in
      their spleen. Further, tuftsin, a known macrophage targeting molecule, was
      tethered to C7P3 and the resulting complex, i.e., C7P3-T/DNA, exhibited
      significantly higher gene expression in cultured mouse peritoneal macrophages as
      compared to unmodified C7P3/DNA complex without any cytotoxicity demonstrating
      the suitability of the conjugate for targeted applications. Conclusively, the
      study demonstrates the potential of the projected conjugates for gene delivery
      for wider biomedical applications.

PMID- 22417620
TI  - The promotion of in vitro vessel-like organization of endothelial cells in
      magnetically responsive alginate scaffolds.
AB  - One of the major challenges in engineering thick, complex tissues such as cardiac
      muscle, is the need to pre-vascularize the engineered tissue in vitro to enable
      its efficient integration with host tissue upon implantation. Herein, we explored
      new magnetic alginate composite scaffolds to provide means of physical
      stimulation to cells. Magnetite-impregnated alginate scaffolds seeded with aortic
      endothelial cells stimulated during the first 7 days out of a total 14 day
      experimental course showed significantly elevated metabolic activity during the
      stimulation period. Expression of proliferating cell nuclear antigen (PCNA)
      indicated that magnetically stimulated cells had a lower proliferation index as
      compared to the non-stimulated cells. This suggests that the elevated metabolic
      activity could instead be related to cell migration and re-organization.
      Immunostaining and confocal microscopy analyses supported this observation
      showing that on day 14 in magnetically stimulated scaffolds without
      supplementation of any growth factors, cellular vessel-like (loop) structures,
      known as indicators of vasculogenesis and angiogenesis were formed as compared to
      cell sheets or aggregates observed in the non-stimulated (control) scaffolds.
      This work is the first step in our understanding of how to accurately control
      cellular organization to form tissue engineered constructs, which together with
      additional molecular signals could lead to a creation of an efficient pre
      vascularized tissue construct with potential applicability for transplantation.

PMID- 22417622
TI  - The intranuclear release of a potential anticancer drug from small nanoparticles
      that are derived from intracellular dissociation of large nanoparticles.
AB  - Transporting drug-containing nanoparticles into the nucleus of cancer cells
      through nucleopores and then releasing the drug intranuclearly provide an
      efficient strategy to overcome the drug resistance mechanisms evolved by cancer
      cells. However, limited by the diameter of nucleopores, nanoparticles capable of
      going through nucleopores should be small enough, whereas the nanoparticles with
      the small size may have short circulation time in blood and low accumulation in
      solid tumors. We solved this dilemma successfully by preparing kinetically frozen
      large compound nanoparticles (sized 128 nm) of complex of
      oligolysine/iridium(III) compound (a potential anticancer drug) that can
      dissociate into small ones in lysosome environment. The small nanoparticles
      retain their small size in cytosol after escaping from the lysosomes, so that
      they can enter the nucleus actively through nucleaopores, with the help of
      oligolysine segments on the surfaces of nanoparticles acting as the nuclear
      targeting moieties. It is significant that the nanoparticles can release the
      contained Ir compound within the nucleus. Further study reveals that the release
      is triggered by DNA interaction with the nanoparticles, which is responsible for
      the observation that the release occurs only in the nucleus. We believe that the
      present study, representing the first example of DNA triggered intranuclear
      release from nanoparticles, will provide a promising pathway for chemotherapy.

PMID- 22417623
TI  - Age-structured dynamic, stochastic and mechanistic simulation model of Salmonella
      Dublin infection within dairy herds.
AB  - In the demand for a decision support tool to guide farmers wanting to control
      Salmonella Dublin (S. Dublin) in Danish dairy herds, we developed an age
      structured stochastic, mechanistic and dynamic simulation model of S. Dublin in
      dairy herds, which incorporated six age groups (neonatal, preweaned calves,
      weaned calves, growing heifers, breeding heifers and cows) and five infection
      states (susceptible, acutely infected, carrier, super shedder and resistant). The
      model simulated population and infection dynamics over a period of 10 years in
      weekly time steps as: 1) population sizes of each of the six age-groups; 2) S.
      Dublin incidence and number of animals in each infection state; and 3) S. Dublin
      related morbidity and mortality in the acutely infected animals. The effects of
      introducing one infectious heifer on the risk of spread of S. Dublin within the
      herd and on the duration of infection were estimated through 1000 simulation
      iterations for 48 scenarios. The scenarios covered all combinations of three herd
      sizes (70, 200 and 400 cows), four hygiene levels indicating infectious contact
      parameters, and four herd susceptibility levels indicating different
      susceptibility parameters for the individual animals in each of the six age
      groups in the herd. The hygiene level was highly influential on the probability
      that the infection spread within the herd, duration of infection and epidemic
      size. The herd susceptibility level was also influential, but not likely to
      provide sufficient prevention and control of infection on its own. Herd size did
      not affect the probability of infection spread upon exposure, but the larger the
      herd the more important were management and housing practices that improve
      hygiene and reduce susceptibility to shorten durations of infection in the herd
      and to increase the probability of extinction. In general, disease and mortality
      patterns followed epidemic waves in the herds. However, an interesting pattern
      was seen for acute infections and abortions in adult cattle after the first 2
      years of infection in herds with poor hygiene and high susceptibility. Repeated
      infections in young stock lead to a high proportion of resistant adult cattle,
      which lead to a dampening effect on acute infections in adults and associated
      abortions. Sensitivity analyses of 24 alternative scenarios showed that a super
      shedder state was not essential to mimic the infection dynamics and persistence
      patterns known from field studies, but a persistent carrier state was required in
      the model to mimic real life S. Dublin infections.

PMID- 22417625
TI  - Eating patterns and lipid levels in older adolescent girls.
AB  - BACKGROUND AND AIMS: Few studies have evaluated the effects of food-based eating
      patterns on adolescent lipid levels. This study examines whether usual adolescent
      eating patterns (ages 9-17 years) predict lipid levels at 18-20 years of age.
      METHODS AND RESULTS: This study uses previously collected data from the
      longitudinal NHLBI Growth and Health Study in which 2379 girls were enrolled at
      ages 9-10 years and followed for ten years. Food-based eating patterns were
      derived from multiple 3-day diet records. After adjusting for age, race,
      socioeconomic status, height, physical activity, and television viewing, girls
      with higher intakes of dairy, fruit and non-starchy vegetables had about a 40-50%
      reduced risk an LDL-C >= 170 mg/dL and non-HDL-C >= 145 mg/dL. Diets
      characterized by higher intakes of dairy and whole grains had similar benefits on
      TC and LDL-C. Girls consuming more fruits and non-starchy vegetables as well as
      more whole grains were much less likely to have high-risk lipid levels. Lean
      meat, poultry and fish when consumed in the context of other healthy eating
      patterns had no adverse effects on lipid levels in late adolescence. In fact when
      consumed with higher amounts of fruit and non-starchy vegetables, lean meat,
      poultry and fish had beneficial effects on HDL. Finally, dietary patterns that
      included more whole grains tended to be associated with lower TG levels.
      CONCLUSION: Healthy childhood eating patterns characterized by higher intakes of
      a variety of fruits, vegetables, whole grains, dairy, lean meat, poultry and fish
      are important modifiable predictors of lipid levels in late adolescence.

PMID- 22417626
TI  - Dissecting rapid estrogen signaling with conjugates.
AB  - Hypothesizing that rapid estrogen signaling could be modulated from different
      estrogen receptors with unique localization patterns, a number of groups have
      attempted to design drug conjugates that target or restrict compounds to specific
      subcellular compartments. This article will briefly discuss the history of using
      conjugates to dissect rapid estrogen signaling and different strategies to
      attempt to target estrogens and antiestrogens to different locations. It will
      also detail some of the potential issues that can arise with different types of
      conjugates, using examples drawn from the authors' own work.

PMID- 22417627
TI  - AlphaB-crystallin in clear cell renal cell carcinoma: tumor progression and
      prognostic significance.
AB  - OBJECTIVES: AlphaB-crystallin (alphaB-crystallin), a small heat shock protein,
      has been reported to be involved in the growth, antiapoptosis, migration, and
      chemoresistance of human malignancies. MATERIALS AND METHODS: alphaB-crystallin
      expression in normal renal and clear cell renal cell carcinoma (ccRCC) tissues
      was examined with two-dimensional (2D) gel electrophoresis assays.
      Immunohistochemistry was conducted to determine the presence of alphaB-crystallin
      positive tumor cells and staining intensity in 50 cases of ccRCC tissue samples.
      The association of alphaB-crystallin protein expression, clinicopathogic
      parameters and prognosis of ccRCC patients was also analyzed with Student's t
      test and Kaplan-Meier analysis. Moreover, Western blot assays were performed to
      detect the protein expression of alphaB-crystallin in normal and tumor tissues
      and the alteration of cell cycle regulators in alphaB-crystallin-overexpressing
      cells. MTT (3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide), BrdU,
      and transwell assays were performed to demonstrate the effects of alphaB
      crystallin overexpression on cell growth, DNA synthesis and cell migration of
      ccRCC cells, respectively. RESULTS: The results showed the up-regulation of
      alphaB-crystallin expression in ccRCC tissues. Overall survival of ccRCC patients
      was significantly correlated with alphaB-crystallin expression in tumor tissues.
      We found that alphaB-crystallin overexpression increased the expression of cyclin
      A and the incorporation of BrdU, which may be related to the enhancement of cell
      growth. Transwell analyses demonstrated that presence of alphaB-crystallin
      overexpression enhanced cell migration in ccRCC cells. Furthermore, rapamycin
      resistance of tumor cells was induced when alphaB-crystallin was overexpressed.
      CONCLUSIONS: Our experimental findings highlight the importance of alphaB
      crystallin in the tumor growth, migration, and target therapy-resistance of ccRCC
      cells.

PMID- 22417629
TI  - Knee function in 10-year-old children and adults with Generalised Joint
      Hypermobility.
AB  - PURPOSE: Knee function is reduced in patients with Benign Joint Hypermobility
      Syndrome. The aim was to study knee function in children and adults with
      Generalised Joint Hypermobility (GJH) and Non-GJH (NGJH)). MATERIALS AND METHODS:
      In a matched comparative study, 39 children and 36 adults (mean age children 10.2
      years; adults 40.3 years) were included, comprising 19 children and 18 adults
      with GJH (Beighton >= 5/9; Beighton >= 4/9), minimum one hypermobile knee, no
      knee pain (children), and 20 children and 18 adults with NGJH (Beighton <5;
      Beighton <4). Totally, 85% of the adults were parents to these children. Knee
      function was determined by self-reported physical fitness (100mm VAS), Knee
      injury and Osteoarthritis Outcome Score (KOOS) (only adults), measured maximum
      isokinetic knee strength (60 degrees /s) and peak vertical jump displacement
      (PVJD), with calculated knee strength balance, Hamstring/Quadriceps (H/Q) ratio
      and peak rate of force development (PRFD). RESULTS: Adults with GJH had lower
      knee function (KOOS: pain, p=0.001; symptoms, p=0.001; Activities of Daily
      Living, p=0.001; Sport/Recreation, p=0.003; knee-related quality of life,
      p<0.001), and H/Q ratio (0.46 vs. 0.54, p=0.046) than adults with NGJH,
      regardless of age and knee pain. Both GJH groups had normal physical fitness,
      isokinetic knee strength, and (only children) H/Q ratio. CONCLUSIONS: Children at
      10 years with GJH have normal, but adults with GJH have impaired knee function.
      To track the risk of developing impaired knee function, children with GJH must be
      followed longitudinally. Meanwhile, attention to knee function may be given to
      children with GJH who have parents presenting GJH.

PMID- 22417628
TI  - Hyperbaric oxygen treatment for inflammatory bowel disease: a systematic review
      and analysis.
AB  - BACKGROUND: Traditionally, hyperbaric oxygen treatment (HBOT) has been used to
      treat a limited repertoire of disease, including decompression sickness and
      healing of problem wounds. However, some investigators have used HBOT to treat
      inflammatory bowel disease (IBD), including Crohn's disease and ulcerative
      colitis. METHODS: Comprehensive searches were conducted in 8 scientific databases
      through 2011 to identify publications using HBOT in IBD. Human studies and animal
      models were collated separately. RESULTS: Thirteen studies of HBOT in Crohn's
      disease and 6 studies in ulcerative colitis were identified. In all studies,
      participants had severe disease refractory to standard medical treatments,
      including corticosteroids, immunomodulators and anti-inflammatory medications. In
      patients with Crohn's disease, 31/40 (78%) had clinical improvements with HBOT,
      while all 39 patients with ulcerative colitis improved. One study in Crohn's
      disease reported a significant decrease in proinflammatory cytokines (IL-1, IL-6
      and TNF-alpha) and one study in ulcerative colitis reported a decrease in IL-6
      with HBOT. Adverse events were minimal. Twelve publications reported using HBOT
      in animal models of experimentally-induced IBD, including several studies
      reporting decreased markers of inflammation or immune dysregulation, including
      TNF-alpha (3 studies), IL-1beta (2 studies), neopterin (1 study) and
      myeloperoxidase activity (5 studies). HBOT also decreased oxidative stress
      markers including malondialdehyde (3 studies) and plasma carbonyl content (2
      studies), except for one study that reported increased plasma carbonyl content.
      Several studies reported HBOT lowered nitric oxide (3 studies) and nitric oxide
      synthase (3 studies) and one study reported a decrease in prostaglandin E2
      levels. Four animal studies reported decreased edema or colonic tissue weight
      with HBOT, and 8 studies reported microscopic improvements on histopathological
      examination. Although most publications reported improvements with HBOT, some
      studies suffered from limitations, including possible publication and referral
      biases, the lack of a control group, the retrospective nature and a small number
      of participants. CONCLUSIONS: HBOT lowered markers of inflammation and oxidative
      stress and ameliorated IBD in both human and animal studies. Most treated
      patients were refractory to standard medical treatments. Additional studies are
      warranted to investigate the effects of HBOT on biomarkers of oxidative stress
      and inflammation as well as clinical outcomes in individuals with IBD.

PMID- 22417630
TI  - Differential diagnosis of localized and systemic amyloidosis based on coagulation
      and fibrinolysis parameters.
AB  - BACKGROUND: A simple assay that can discriminate between localized and systemic
      amyloidosis is needed. METHODS: Coagulation and fibrinolysis parameters were
      measured in subjects with active or progressive systemic amyloidosis (Group A; 9
      patients), systemic amyloidosis in complete remission (Group B; 6 patients),
      localized AL amyloidosis (Group C; 6 patients), monoclonal gammopathy of
      undetermined significance (Group D; 5 patients), chronic glomerulonephritis with
      proteinuria (Group E; 22 patients), or glomerulonephritis in complete remission
      (Group F; 11 patients). RESULTS: No significant differences were noted between
      Group A and the other groups in the international normalized ratio of prothrombin
      time, activated partial thromboplastin time, and levels of antithrombin and
      plasminogen. Levels of thrombin-antithrombin (TAT) complexes, fibrinogen,
      fibrinogen degradation product d-dimers, and plasmin-alpha2-plasmin inhibitor
      complexes (PIC) were significantly elevated in Group A. All patients that showed
      TAT complexes, fibrinogen, and PIC levels greater than 4.2 ng/mL, 399 mg/dL, and
      1.4 MUg/mL, respectively, had active or progressive systemic amyloidosis. All
      patients with TAT complex levels less than 3.6 ng/mL, fibrinogen levels less than
      355 mg/dL, and PIC levels less than 0.9 MUg/mL had localized AL amyloidosis.
      CONCLUSION: Analyses of TAT complexes, fibrinogen, and PIC can be used to
      differentiate localized AL amyloidosis from systemic amyloidosis.

PMID- 22417631
TI  - Dietary factors associated with metabolic syndrome in Brazilian adults.
AB  - BACKGROUND: Metabolic Syndrome (MS) is defined as the association of numerous
      factors that increase cardiovascular risk and diet is one of the main factors
      related to increase the MS in the population. This study aimed to evaluate the
      association of diet on the presence of MS in an adult population sample.
      METHODOLOGY: 305 adults were clinically screened to participate in a lifestyle
      modification program. Anthropometric assessments included waist circumference
      (WC), body fat and calculated BMI (kg/m2) and muscle-mass index (MMI kg/m2).
      Dietary intake was estimated by 24 h dietary recall. Fasting blood was used for
      biochemical analysis. MS was diagnosed using NCEP-ATPIII (2001) criteria with
      adaptation for glucose (>=100 mg/dL). Logistic regression (Odds ratio) was
      performed in order to determine the odds ratio for developing MS according to
      dietary intake. RESULTS: An adequate intake of fruits, OR=0.52 (CI:0.28-0.98),
      and an intake of more than 8 different items in the diet (variety), OR=0.31
      (CI:0.12-0.79) showed to be a protective factor against a diagnosis of MS.
      Saturated fat intake greater than 10% of total caloric value represented a risk
      for MS diagnosis, OR=2.0 (1.04-3.84). CONCLUSION: Regarding the dietary aspect, a
      risk factor for MS was higher intake of saturated fat, and protective factors
      were high diet variety and adequate fruit intake.

PMID- 22417632
TI  - Disentangling the effects of cognitive development and linguistic expertise: a
      longitudinal study of the acquisition of English in internationally-adopted
      children.
AB  - Early language development is characterized by predictable changes in the words
      children produce and the complexity of their utterances. In infants, these
      changes could reflect increasing linguistic expertise or cognitive maturation and
      development. To disentangle these factors, we compared the acquisition of English
      in internationally-adopted preschoolers and internationally-adopted infants.
      Parental reports and speech samples were collected for 1 year. Both groups showed
      the qualitative shifts that characterize first-language acquisition. Initially,
      they produced single-word utterances consisting mostly of nouns and social words.
      The appearance of verbs, adjectives and multiword utterances was predicted by
      vocabulary size in both groups. Preschoolers did learn some words at an earlier
      stage than infants, specifically words referring to the past or future and
      adjectives describing behavior and internal states. These findings suggest that
      cognitive development plays little role in the shift from referential terms to
      predicates but may constrain children's ability to learn some abstract words.

PMID- 22417633
TI  - Editorial: effective bio-economic approaches for stem cell therapy and
      regenerative medicine.

PMID- 22417634
TI  - Disseminated aspergillosis associated with tsunami lung.
AB  - Many survivors of the tsunami that occurred following the Great East Japan
      Earthquake on March 11, 2011, contracted a systemic disorder called "tsunami
      lung," a series of severe systemic infections following aspiration pneumonia
      caused by near drowning in the tsunami. Generally,  the cause of aspiration
      pneumonia is polymicrobial, including fungi and aerobic and anaerobic bacteria,
      but Aspergillus infection is rarely reported. Here we report a case of tsunami
      lung complicated by disseminated aspergillosis, as diagnosed during autopsy.

PMID- 22417636
TI  - The functional genomics of an eco-evolutionary feedback loop: linking gene
      expression, trait evolution, and community dynamics.
AB  - Feedbacks between ecological and evolutionary change may play important roles in
      community and ecosystem functioning, but a complete eco-evolutionary feedback
      loop has not been demonstrated at the community level, and we know little about
      molecular mechanisms underlying this kind of eco-evolutionary dynamics. In
      predator-prey (rotifer-alga) microcosms, cyclical changes in predator abundance
      generated fluctuating selection for a heritable prey defence trait, cell
      clumping. Predator population growth was affected more by prey evolution than by
      changes in prey abundance, and changes in predator abundance drove further prey
      evolution, completing the feedback loop. Within a predator-prey cycle, genes up
      regulated as clumping declined were down-regulated as clumping increased, and
      vice-versa. Genes changing most in expression tended to be associated with
      defence or its cost. Expression patterns of individual genes differed greatly
      between consecutive cycles (often reversing direction), suggesting that a
      particular phenotype may be produced by several (perhaps many) different gene
      transcription pathways.

PMID- 22417637
TI  - Synthesis and biological activity of 23-ethylidene-26-hydroxy-22-oxocholestane
      derivatives from spirostanic sapogenins.
AB  - The synthesis and biological evaluation of three new cholestane frameworks of the
      type: (25R)-3beta,16beta-Diacetoxy-23-ethylidene-26-hydroxy-22-oxocholestane,
      starting from spirostanic sapogenins of the 25R series, is described. The
      compounds were obtained by the reductive cleavage of the F ring of 22-oxo
      23(1),26-epoxycholestane derivatives using 9-BBN. These modified derivatives
      exhibit cytotoxic activity against CEM and MCF7 cells and are able to induce
      apoptosis in them. Its effect on the cell cycle was determined.

PMID- 22417635
TI  - Persistent lipophilic environmental chemicals and endometriosis: the ENDO Study.
AB  - BACKGROUND: An equivocal literature exists regarding the relation between
      persistent organochlorine pollutants (POPs) and endometriosis in women, with
      differences attributed to methodologies. OBJECTIVES: We assessed the association
      between POPs and the odds of an endometriosis diagnosis and the consistency of
      findings by biological medium and study cohort. METHODS: Using a matched cohort
      design, we assembled an operative cohort of women 18-44 years of age undergoing
      laparoscopy or laparotomy at 14 participating clinical centers from 2007 to 2009
      and a population-based cohort matched on age and residence within a 50-mile
      catchment area of the clinical centers. Endometriosis was defined as visualized
      disease in the operative cohort and as diagnosed by magnetic resonance imaging in
      the population cohort. Logistic regression analysis was used to estimate odds
      ratios (ORs) and 95% confidence intervals (CIs) for each POP in relation to an
      endometriosis diagnosis, with separate models run for each medium (omental fat in
      the operative cohort, serum in both cohorts) and cohort. Adjusted models included
      age, body mass index, breast-feeding conditional on parity, cotinine, and lipids.
      RESULTS: Concentrations were higher in omental fat than in serum for all POPs. In
      the operative cohort, gamma-hexachlorocyclohexane (gamma-HCH) was the only POP
      with a significant positive association with endometriosis [per 1-SD increase in
      log-transformed gamma-HCH: adjusted OR (AOR) = 1.27; 95% CI: 1.01, 1.59]; beta
      HCH was the only significant predictor in the population cohort (per 1-SD
      increase in log-transformed beta-HCH: AOR = 1.72; 95% CI: 1.09, 2.72).
      CONCLUSIONS: Using a matched cohort design, we found that cohort-specific and
      biological-medium-specific POPs were associated with endometriosis, underscoring
      the importance of methodological considerations when interpreting findings.

PMID- 22417638
TI  - Synthesis and SAR studies of phenanthroindolizidine and phenanthroquinolizidine
      alkaloids as potent anti-tumor agents.
AB  - A series of phenanthroindolizidine and phenanthroquinolizidine alkaloids and
      their 14-amino-derivatives (1-44) were prepared and systematically evaluated for
      their anti-tumor activities against A549 and HL60 cell lines. The bioassay
      results showed that most of these alkaloids possess good anti-tumor activities.
      Especially, compounds 15, 22, 28, 33-36, 40 and 42 displayed low nanomolar or
      subnanomolar levels of anti-tumor activity. The configuration of (13aS,14S)-14
      hydroxyphenanthroindolizidines and (14aR,15R)-15-hydroxyphenanthroquinolizidines
      was confirmed to be optimal. 14-Amino-phenanthroindolizidines with increased
      polarity possess good anti-tumor activity, especially for compounds 26 and 28.
      Most of the phenanthroquinolizidine alkaloids exhibited higher anti-tumor
      activity than that of phenanthroindolizidine alkaloids. Our present study
      provides fundamental support for development and optimization of
      phenanthroindolizidine and phenanthroquinolizidine alkaloids as potential anti
      tumor drugs.

PMID- 22417639
TI  - Enaminones 12. An explanation of anticonvulsant activity and toxicity per Linus
      Pauling's clathrate hypothesis.
AB  - The x-ray crystal structure of 3-((5-methylisoxazol-3-yl)amino)-5-methylcyclohex
      2-enone (12b) and 3-((5-methylisoxazolyl-3-yl)amino)-5,5-dimethylcyclohex-2-enone
      (12c) were determined and correlated to their anticonvulsant activity in mice and
      rats. A hypothesis for the toxicity of the analogs are advanced. In addition, a
      series of 5-methyl-N-(3-oxocyclohex-1-enyl)-isoxazole-3-carboxamides were
      synthesized and evaluated for anticonvulsant activity. These compounds were
      compared to the activity of the corresponding amino and aminomethyl enaminones.
      Additional investigation involved the synthesis and evaluation of a
      trifluoromethyl analog of the active isoxazole tert-butyl 4-(5-methisoxazol-3-yl
      amino)-6-methyl-2-oxo-cyclohex-3-ene carboxylate (4f).

PMID- 22417640
TI  - Antifungal peptides at membrane interaction.
AB  - Many drugs are available for the treatment of systemic or superficial mycoses,
      but only a limited number of them are effective antifungal drugs, devoid of toxic
      and undesirable side effects. Furthermore, resistance development and fungistatic
      rather than fungicidal activities represent limitations of current antifungal
      therapy. Therefore an urgent need for a new generation of antifungal agents
      remains. We recently synthesised a set of linear and cyclic peptides
      characterized by sequences typical of membrane-active antimicrobial peptides
      (AMP). AMT2, cyclo-AMT2, AMT3 and cyclo-AMT3 (Scheme 1) were tested against
      different yeast species and exhibited general antifungal activity, with a
      specificity against Cryptococcus neoformans. To evaluate the role of the membrane
      cell in the mechanism of antifungal activity, we investigated the conformational
      behaviour of AMT2, cyclo-AMT2, AMT3 and cyclo-AMT3 in different bio-membrane
      mimicking systems using a combined approach based on spectroscopy and microscopy
      techniques. Our data highlight the behaviour of the peptides to interact with the
      bilayer surface, excluding their ability to destabilize or permeabilize the
      fungal cell wall. Microbial membrane, indeed, may be an important platform for
      specific interactions of peptides with specific targets involved in the cell wall
      synthesis.

PMID- 22417641
TI  - ELIXIR: a distributed infrastructure for European biological data.

PMID- 22417642
TI  - The late and moderate preterm baby.

PMID- 22417643
TI  - Health outcomes in infancy and childhood of moderate and late preterm infants.
AB  - There has been a long-held belief that outcomes for babies born at moderate and
      late preterm gestations do not differ substantially from those of infants born at
      full term. This has recently been challenged by studies highlighting an increased
      risk of adverse neonatal outcomes, and of poorer cognitive, behavioural and
      educational outcomes in this population. Data about the effects of birth at
      moderate and late preterm gestations on later health outcomes are limited, but
      emerging evidence suggests that ongoing physical health may also be worse in
      those born just a few weeks before full term. This review summarises the
      available evidence, considers the factors influencing health outcomes and
      discusses the implications for the planning and provision of children's health
      care services.

PMID- 22417644
TI  - Characterization of glucagon-like peptide 1 receptor (GLP1R) gene in chickens:
      functional analysis, tissue distribution, and identification of its transcript
      variants.
AB  - Glucagon-like peptide 1 (GLP1) receptor plays a critical role in mediating the
      biological actions of GLP1 in mammals and fish; however, the gene structure,
      expression, and functionality of GLP1 receptor (GLP1R) remain largely unknown in
      birds. In this study, the full-length cDNA of chicken GLP1R (cGLP1R) was first
      cloned from brain tissue by reverse transcription PCR. The putative cGLP1R is 459
      amino acids in length and shares high amino acid sequence identity with that of
      human (79%), rat (80%), and Xenopus (75%). Using a pGL3-CRE luciferase reporter
      system, we found that cGLP1R expressed in Chinese hamster ovary cells could be
      potently activated by cGLP1 (EC(50), 0.11 nM) but not by other structurally
      related peptides, indicating that cGLP1R is a functional receptor specific to
      cGLP1. Interestingly, in addition to identification of the transcript encoding
      cGLP1R of 459 amino acids, eight transcript variants, which were generated by
      alternative mRNA splicing and predicted to encode either C-terminally or N
      terminally truncated cGLP1Rs, were also identified from chicken brain or testis.
      In line with this finding, multiple cGLP1R transcripts were detected to be
      expressed in most chicken tissues examined, including pancreas, gastrointestinal
      tract, and various brain regions by reverse transcription PCR. Using the dual
      luciferase reporter assay system, we further found that the 5'-flanking region of
      cGLP1R gene displays promoter activities in cultured HepG2 and HEK293 cells,
      suggesting that it may control cGLP1R gene transcription in chicken tissues,
      including nonpancreatic tissues. Taken together, the results from the present
      study establish a molecular basis to investigate the roles of GLP1 in chickens.

PMID- 22417645
TI  - In ovo leptin administration inhibits chorioallantoic membrane angiogenesis in
      female chicken embryos through the STAT3-mediated vascular endothelial growth
      factor (VEGF) pathway.
AB  - Previous studies indicate that leptin regulates placental angiogenesis and fetal
      growth in mammals and that in ovo leptin administration affects embryonic
      development and hatch weight in the chicken. To test the hypothesis that leptin
      affects embryonic growth through modifying chorioallantoic membrane (CAM)
      angiogenesis, we injected 0.5 MUg of recombinant murine leptin into the albumen
      of fertilized eggs before incubation. On embryonic day 12 (E12), the number and
      the total area of blood vessels on CAM were measured, and expression of genes
      involved in angiogenesis was quantitated to show the possible mechanisms. Leptin
      in ovo administration decreased (P < 0.05) both the total area of blood vessels
      and the number of small-sized capillaries on CAM of E12 female chicken embryos,
      which coincided with significantly decreased (P < 0.05) embryo weight on E12 and
      BW at hatching. Vascular endothelial growth factor (VEGF) and inducible and
      endothelial nitric oxide synthases (iNOS and eNOS) were all downregulated (P <
      0.05) in CAM both at the mRNA and protein/activity levels with reduced (P < 0.05)
      nitric oxide (NO) concentration in chorioallantoic fluid of female embryos.
      Furthermore, signal transducer and activator of transcription-3 (STAT3) was found
      to be diminished (P < 0.05) both at the mRNA and protein levels and associated
      with decreased (P < 0.05) binding of STAT3 to VEGF promotor in the CAM of leptin
      treated E12 female embryos. These data suggest that in ovo leptin administration
      affects CAM angiogenesis and embryo growth in female chicken embryos, probably
      through STAT3-mediated VEGF/NO pathways.

PMID- 22417646
TI  - Structure of child and adult past counterfactuals, and implications for
      acquisition of the construction.
AB  - Children start producing if p, q conditionals relatively late. Past
      counterfactuals (PCFs), for example 'If she had shut the cage, the rabbit
      wouldn't have escaped', are particularly problematic for children; despite
      evidence of comprehension in the preschool years, children aged eleven are still
      making production errors in PCF structure (Crutchley, 2004). Working within a
      usage-based framework, the present study explores whether PCFs in the
      conversational component of the British National Corpus show structural
      similarities to the set of PCF structures produced by six- to eleven-year-old
      children in an elicitation task. Adult PCFs are found to be both rare in
      spontaneous conversation and very varied in structure. Low token frequency and
      high type frequency are hypothesized to account partly for children's late
      acquisition of the PCF construction. However, regularities in the use of subjects
      and verbs in adult PCFs are hypothesized to assist children's acquisition of the
      construction.

PMID- 22417647
TI  - Value of self-performed joint counts in rheumatoid arthritis patients near
      remission.
AB  - INTRODUCTION: To determine the validity and reliability of patients' self
      performed joint counts compared to joint counts by professional assessors in
      rheumatoid arthritis (RA) patients in different disease activity states. METHODS:
      In patients with established RA we determined the inter-rater reliability of
      joint counts performed by an independent evaluator and the patient using
      intraclass correlation (ICC), and agreement on activity in individual joints by
      kappa statistics. We also performed longitudinal analyses to assess consistency
      of assessments over time. Finally, we investigated the concordance of joint
      counts of different assessors in patients with different levels of disease
      activity. RESULTS: The reliability of patient self-performed joint counts was
      high when compared to independent objective assessment (ICC; 95%confidence
      interval (CI)) for the assessment of swelling (0.32; 0.15 to 0.46) and tenderness
      (0.75; 0.66 to 0.81), with higher agreement for larger joints (kappa: 0.57 and
      0.45, respectively) compared to smaller joints (metacarpo-phalangeal joint
      (MCPs): 0.31 and 0.45; and proximal interphalangeal joint (PIPs): 0.22 and 0.47,
      for swelling and tenderness, respectively).Patients in remission according to the
      Simplified Disease Activity Index (SDAI <= 3.3) showed better concordance of the
      joint counts (swollen joint count (SJC) ties 25/37, tender joint count (TJC) ties
      26/37) compared to moderate/high disease activity states (SDAI > 11; MDA/HDA: SJC
      ties 9/72, TJC ties 21/72). Positive and negative predictive values regarding the
      presence of SDAI remission were reasonably good (0.86 and 0.95, respectively). A
      separate training session for patients did not improve the reliability of joint
      assessment. The results were consistent in the longitudinal analyses.
      CONCLUSIONS: Self-performed joint counts are particularly useful for monitoring
      in patients having attained remission, as these patients seem able to detect
      state of remission.

PMID- 22417648
TI  - Expression patterns of heat shock protein 25 in carbon tetrachloride-induced rat
      liver injury.
AB  - Heat shock protein 25 (Hsp25) is a molecular chaperone playing roles in
      cytoprotection. We investigated the distribution and localization of Hsp25
      expression in CCl(4)-induced rat hepatic lesions; liver samples were obtained
      from 3 h to 10 days after a single oral administration of CCl(4).
      Immunohistochemically, Hsp25-positive hepatocytes started to appear in the
      perivenular area at 6 h after CCl(4) administration. Their number and strength
      increased till day 1. Expression of Hsp25 mRNA significantly increased after 3 h
      and proceeded to increase with time till day 1. Apoptotic hepatocytes were
      detected around the perivenular area after 6 h. The area where Hsp25-positive
      hepatocytes were observed till day 1 corresponded to the area where apoptotic
      hepatocytes were seen. On days 2 and 3, degenerative and/or necrotic hepatocytes
      in the perivenular area were replaced by macrophages reacting to ED1 (for CD68)
      and ED2 (for CD163); Hsp25 expression was seen in hepatocytes around the
      perivenular area and there was a close relationship of reactive macrophages with
      Hsp25-positive hepatocytes, suggesting a potential role for Hsp25 in suppressing
      injury by inflammation. The mRNA expression of tumor necrosis factor-alpha,
      monocyte chemoattractant protein-1 and osteopontin, which can be produced by
      infiltrating macrophages, corresponded to that of Hsp25 from day 1 to day 3;
      these factors might be related to the induction of Hsp25 expression. The shift of
      the Hsp25 expression pattern in the liver lesion might have depended on
      microenvironmental conditions evoked by interactions between necrobiotic
      hepatocytes and infiltrating macrophages. Thus, Hsp25 expression analyses should
      be beneficial for evaluations of hepatotoxicants.

PMID- 22417649
TI  - Synthesis and antiviral activity of 6-deoxycyclopropavir, a new prodrug of
      cyclopropavir.
AB  - Synthesis of 6-deoxycyclopropavir (10), a prodrug of cyclopropavir (1) and its in
      vitro and in vivo antiviral activity is described. 2-Amino-6-chloropurine
      methylenecyclopropane 13 was transformed to its 6-iodo derivative 14 which was
      reduced to prodrug 10. It is converted to cyclopropavir (1) by the action of
      xanthine oxidase and this reaction can also occur in vivo. Compound 10 lacked
      significant in vitro activity against human cytomegalovirus (HCMV), human herpes
      virus 1 and 2 (HSV-1 and HSV-2), human immunodeficiency virus type 1 (HIV-1),
      human hepatitis B virus (HBV), Epstein-Barr virus (EBV), vaccinia virus and
      cowpox virus. In contrast, prodrug 10 given orally was as active as cyclopropavir
      (1) reported previously [Kern, E. R.; Bidanset, D. J.; Hartline, C. B.; Yan, Z.;
      Zemlicka, J.; Quenelle, D. C. et al. Antimicrob. Agents Chemother. 2004, 48,
      4745] against murine cytomegalovirus (MCMV) infection in mice and against HCMV in
      severe combined immunodeficient (SCID) mice.

PMID- 22417650
TI  - Dead space fraction changes during PEEP titration following lung recruitment in
      patients with ARDS.
AB  - BACKGROUND: Elevated dead space fraction (the ratio of dead space to tidal volume
      [V(D)/V(T)]) is a feature of ARDS. PEEP can partially reverse atelectasis,
      prevent alveoli recollapse, and improve lung compliance and gas exchange in
      patients with ARDS. However, whether V(D)/V(T) variables have a close
      relationship with PEEP and collapse alveolar recruitment remains under
      recognized. Meanwhile, few clinicians titrate PEEP in consideration of changes in
      V(D)/V(T). Therefore, we performed the study to evaluate V(D)/V(T), arterial
      oxygenation, and compliance changes during PEEP titration following lung
      recruitment in ARDS patients. METHODS: Twenty-three ARDS patients ventilated in
      volume-controlled mode were enrolled in the study. Sustained inflation (40 cm
      H2O, 30 s) was used as a recruitment maneuver, followed by decremental PEEP
      changes from 20 to 6 cm H2O, in steps of 2 cm H2O, and then to 0 cm H2O.
      V(D)/V(T), pulmonary mechanics parameters, gas exchange parameters, and
      hemodynamic parameters were recorded after 20 min at each PEEP step. RESULTS:
      Compared with V(D)/V(T) at the PEEP levels of 20 cm H2O and 0 cm H2O, V(D)/V(T)
      was significantly lower at 12 cm H2O (P = .02), and compliance of the static
      respiratory system (C(RS)) was significantly higher at pressure step 12/10 cm H2O
      (P < .001). Compared with P(aCO2) at the PEEP level of 20 cm H2O, P(aCO2) was
      significantly lower at 12 cm H2O (P < .001). Arterial oxygenation values and
      functional residual capacity were reduced gradually during PEEP, decreasing from
      20 cm H2O to 0 cm H2O. CONCLUSIONS: A significant change of V(D)/V(T), compliance
      and arterial oxygenation could be induced by PEEP titration in subjects with
      ARDS. Optimal PEEP in these subjects was 12 cm H2O, because at this pressure
      level the highest compliance in conjunction with the lowest V(D)/V(T) indicated a
      maximum amount of effectively expanded alveoli. Monitoring of V(D)/V(T) was
      useful for detecting lung collapse and for establishing open-lung PEEP after a
      recruitment maneuver.

PMID- 22417651
TI  - Adriamycin dose and time effects on cell cycle, cell death, and reactive oxygen
      species generation in leukaemia cells.
AB  - We investigate the relative importance of the different mechanisms of Adriamycin,
      an anthracycline, and their interrelations, in particular the link between cell
      cycle arrest, cell death, and generation of reactive oxygen species (ROS) that is
      suspected to be the origin of cardiotoxic side-effects. We introduced a lifetime
      fluorescence based technology and used videomicrofluorometry, two efficient
      analytical methods. We show that depending on the doses and time after
      incubation, ADR will not reach the same compartments (nucleus, mitochondria,
      cytosol) in the cells, having consequences on the production of ROS, growth
      arrest pathways and cell death pathways.

PMID- 22417652
TI  - Root proximity and cortical bone thickness effects on the success rate of
      orthodontic micro-implants using cone beam computed tomography.
AB  - OBJECTIVE: To evaluate factors (root proximity and cortical bone thickness)
      affecting the success rate of orthodontic micro-implants (OMIs) using cone-beam
      computed tomography (CBCT) images. MATERIALS AND METHODS: We examined 172 OMIs
      (1.2-1.3 mm in diameter, 8 mm in length) implanted into the maxillary buccal
      alveolar bone of 94 patients (33 men, 61 women) with malocclusion. Root proximity
      and cortical bone thickness were measured, and the correlations between these
      measurements and OMI success rates were evaluated. RESULTS: The overall success
      rate was 90.7% (156/172). The success rate increased as the distance between the
      root surface and OMI increased, showing a highly significant statistical
      correlation (P < .05). As the cortical bone thickness increased, the success rate
      increased, showing a slight, nonsignificant correlation (P > .05). Thus, the
      success rate of OMIs was affected more significantly by root proximity than
      cortical bone thickness. CONCLUSIONS: When inserting OMIs, increasing the
      distance from the OMI to the root surface will significantly improve success
      rates.

PMID- 22417653
TI  - Cervical vertebral maturation as a biologic indicator of skeletal maturity.
AB  - OBJECTIVE: To identify and review the literature regarding the reliability of
      cervical vertebrae maturation (CVM) staging to predict the pubertal spurt.
      MATERIALS AND METHODS: The selection criteria included cross-sectional and
      longitudinal descriptive studies in humans that evaluated qualitatively or
      quantitatively the accuracy and reproducibility of the CVM method on lateral
      cephalometric radiographs, as well as the correlation with a standard method
      established by hand-wrist radiographs. RESULTS: The searches retrieved 343 unique
      citations. Twenty-three studies met the inclusion criteria. Six articles had
      moderate to high scores, while 17 of 23 had low scores. Analysis also showed a
      moderate to high statistically significant correlation between CVM and hand-wrist
      maturation methods. There was a moderate to high reproducibility of the CVM
      method, and only one specific study investigated the accuracy of the CVM index in
      detecting peak pubertal growth. CONCLUSIONS: This systematic review has shown
      that the studies on CVM method for radiographic assessment of skeletal maturation
      stages suffer from serious methodological failures. Better-designed studies with
      adequate accuracy, reproducibility, and correlation analysis, including studies
      with appropriate sensitivity-specificity analysis, should be performed.

PMID- 22417654
TI  - The B55alpha-containing PP2A holoenzyme dephosphorylates FOXO1 in islet beta
      cells under oxidative stress.
AB  - The FOXO1 (forkhead box O1) transcription factor influences many key cellular
      processes, including those important in metabolism, proliferation and cell death.
      Reversible phosphorylation of FOXO1 at Thr(24) and Ser(256) regulates its
      subcellular localization, with phosphorylation promoting cytoplasmic
      localization, whereas dephosphorylation triggers nuclear import and
      transcriptional activation. In the present study, we used biochemical and
      molecular approaches to isolate and link the serine/threonine PP2A (protein
      phosphatase 2A) holoenzyme containing the B55alpha regulatory subunit, with
      nuclear import of FOXO1 in pancreatic islet beta-cells under oxidative stress, a
      condition associated with cellular dysfunction in Type 2 diabetes. The mechanism
      of FOXO1 dephosphorylation and nuclear translocation was investigated in
      pancreatic islet INS-1 and betaTC-3 cell lines subjected to oxidative stress. A
      combined chemical cross-linking and MS strategy revealed the association of FOXO1
      with a PP2A holoenzyme composed of the catalytic C, structural A and B55alpha
      regulatory subunits. Knockdown of B55alpha in INS-1 cells reduced FOXO1
      dephosphorylation, inhibited FOXO1 nuclear translocation and attenuated oxidative
      stress-induced cell death. Furthermore, both B55alpha and nuclear FOXO1 levels
      were increased under hyperglycaemic conditions in db/db mouse islets, an animal
      model of type 2 diabetes. We conclude that B55alpha-containing PP2A is a key
      regulator of FOXO1 activity in vivo.

PMID- 22417655
TI  - FT011, a new anti-fibrotic drug, attenuates fibrosis and chronic heart failure in
      experimental diabetic cardiomyopathy.
AB  - AIMS: Cardiac remodelling in diabetes includes pathological accumulation of
      extracellular matrix and myocyte hypertrophy that contribute to heart
      dysfunction. Attenuation of remodelling represents a potential therapeutic
      target. We tested this hypothesis using a new anti-fibrotic drug, FT011
      (Fibrotech Therapeutics Pty Ltd), on diabetic Ren-2 rats, a model which
      replicates many of the structural and functional manifestations of diabetic
      cardiomyopathy in humans. METHODS AND RESULTS: Homozygous Ren-2 rats were
      randomized to receive streptozotocin or vehicle then further randomized to FT011
      (200 mg/kg/day) or vehicle treatment for 6 weeks. Prior to tissue collection,
      cardiac function was assessed via echocardiography and cardiac catheterization.
      Total collagen deposition and cardiomyocyte hypertrophy were assessed by
      picrosirius red and haematoxylin and eosin staining, respectively. Macrophage
      interstitial infiltration and type I and III collagen were quantitated by
      immunostaining. Without affecting blood pressure or hyperglycaemia, treatment of
      diabetic rats with FT011 significantly attenuated interstitial fibrosis (total
      collagen, 5.09 +/-1.28 vs, 2.42 +/-0.43%/area; type I collagen, 4.09 +/-1.16 vs.
      1.42 +/-0.38%/area; type III collagen, 1.52 +/-0.33 vs. 0.71 +/-0.14 %/area; P <
      0.05), cardiomyocyte hypertrophy (882 +/-38 vs. 659 +/-28 um(2); P < 0.05), and
      interstitial macrophage influx (66 +/-5.3 vs, 44 +/-7.9 number/section; P <
      0.05). Cardiac myopathic dilatation was normalized, as evidenced by reduced left
      ventricular inner diameter at diastole (0.642 +/-0.016 vs. 0.577 +/-0.024 cm),
      increased ejection fraction (75 +/-1.1 vs. 83 +/-1.2%) and preload recruitable
      stroke work relationship (44 +/-6.7 vs. 77 +/-6.3 slope-mmHg; P < 0.05), and
      reduced end-diastolic pressure-volume relationship (0.059 +/-0.011 vs. 0.02 +/
      0.003 slope-mmHg/MUL; P < 0.05). CONCLUSIONS: A direct anti-fibrotic agent,
      FT011, attenuates cardiac remodelling and dysfunction in experimental diabetic
      cardiomyopathy. This represents a novel therapy for the treatment of diabetic
      cardiomyopathy associated with cardiac fibrosis and hypertrophy.

PMID- 22417656
TI  - Evidence for indirect effects of pain catastrophizing on clinical pain among
      myofascial temporomandibular disorder participants: the mediating role of sleep
      disturbance.
AB  - Sleep disturbance and pain catastrophizing are important mediators of the chronic
      pain experience. To date, these factors have not been considered concurrently
      despite compelling theoretical rationale to do so. In the present study, we
      examined whether pain catastrophizing not only has direct effects on clinical
      pain and pain-related interference, but also indirect effects through its
      association with sleep disturbance. We evaluated this hypothesis using a cohort
      (n=214) of myofascial temporomandibular disorder participants using a statistical
      bootstrapping technique recommended for tests of indirect effects. Results
      suggested that pain catastrophizing was associated with greater sleep
      disturbance, and that a significant portion of variance in clinical pain severity
      and pain-related interference attributable to pain catastrophizing was mediated
      by sleep disturbance. Supplementary analyses revealed that the rumination
      component of catastrophizing seemed to be indirectly related to clinical outcomes
      through sleep disturbance. No evidence for indirect effects was observed for
      helplessness and magnification components. These results suggest that rumination
      about pain may contribute to clinical pain indirectly through alterations in
      sleep. Prospective studies are needed to examine lagged associations between
      these constructs. These findings have important theoretical and clinical
      implications. Critically, interventions that reduce pain catastrophizing may
      concurrently improve sleep and clinical pain.

PMID- 22417657
TI  - Lower limb pain and locomotor disability.

PMID- 22417658
TI  - Characteristics of patients with psoriasis and Type 2 diabetes in a central China
      case-control study.

PMID- 22417659
TI  - CPAP has no effect on clearance, sputum properties, or expectorated volume in
      cystic fibrosis.
AB  - BACKGROUND: Positive expiratory pressure (PEP) is used for airway clearance in
      cystic fibrosis (CF) patients. Hypertonic saline (HTS) aerosol increases sputum
      expectoration volume and may improve respiratory secretion properties. CPAP may
      also be used to maintain airway patency and  mobilize secretions. To evaluate if
      CPAP would increase the beneficial clearance effect of HTS in subjects with CF,
      we investigated the effects of CPAP alone and CPAP followed by HTS on sputum
      physical properties and expectoration volume in CF subjects. METHODS: In this
      crossover study, 15  CF subjects (mean age 19 y old) were randomized to
      interventions, 48 hours apart: directed coughs (control), CPAP at 10 cm H(2)O,
      HTS 7%, and both CPAP and HTS (CPAP+HTS). Sputum collection was performed at
      baseline and after interventions. Expectorated volume was determined and in 
      vitro sputum properties were analyzed for contact angle and cough clearability.
      RESULTS: There were no significant differences between any treatment in arterial
      blood pressure, heart rate, or pulse oximetry, between the 2 time points. HTS and
      CPAP+HTS improved cough clearability by 50% (P  = .001) and expectorated volume
      secretion by 530% (P = .001). However, there were no differences between control
      and CPAP on sputum contact angle, cough clearability, or volume of expectorated
      secretion. CONCLUSIONS: CPAP alone had no effect on mucus clearance, sputum
      properties, or  expectorated volume, and did not potentiate the effect of HTS
      alone in CF subjects.

PMID- 22417660
TI  - Overproduction of the multidrug efflux pump MexEF-OprN does not impair
      Pseudomonas aeruginosa fitness in competition tests, but produces specific
      changes in bacterial regulatory networks.
AB  - It is generally assumed that acquisition of antibiotic resistance leads to non
      specific fitness costs. We have tested the alternative hypothesis that
      acquisition of antibiotic resistance may not always produce a general burden to
      the microorganisms, as measured in competition tests, but rather lead to specific
      changes in bacterial physiology. To this end we studied the effect of
      overproducing the multidrug efflux pump MexEF-OprN on Pseudomonas aeruginosa due
      to a constitutive activation of MexT, the transcriptional activator of the mexEF
      oprN genes. We found that overexpression of MexEF-OprN does not cause a
      significant decrease in P.aeruginosa fitness in classical competition tests,
      indicating the absence of a large metabolic burden and that any possible negative
      effects might be observed only under specific conditions. Transcriptomic analyses
      revealed that overexpression of MexEF-OprN results in reduced expression of
      several quorum-sensing regulated genes. We traced back this phenotype to a delay
      in PQS production due to extrusion of kynurenine, a PQS precursor, through the
      efflux pump. Type VI secretion was also impaired. A Caenorhabditis elegans model
      demonstrated that overproduction of MexEF-OprN impairs virulence in P.aeruginosa.
      This effect was mainly due to the activity of the efflux pump, and not to MexT,
      despite the fact that the latter regulates Type III and Type VI secretion.
      Altogether, these data indicate that antibiotic resistance can produce
      modifications in the bacterial regulatory networks with relevant consequences for
      the bacterial behaviour in specific ecosystems, including the infected host.

PMID- 22417661
TI  - An evaluation of nursing students' communication ability during practical
      clinical training.
AB  - OBJECTIVES: To investigate communication abilities and other influential factors
      on nursing students at the beginning of clinical practical session. METHODS: A
      cluster sample of 312 nursing students from 22 nursing colleges or universities
      was recruited. Communication ability of these participants was evaluated by 4
      questionnaires for demographic data, clinical communication behavior, treatment
      communication skills and interpersonal communication skills at the beginning of
      clinical practical session. RESULTS: The stability and accuracy of the
      questionnaires were established with an overall content validity index of 0.78,
      the Cronbach's Alpha index ranged from 0.872 to 0.951, and the letter index
      fluctuates from 0.85 to 0.89. Results demonstrated that 88.1% of the nursing
      students require extra training in clinical communication behavior, treatment
      communication skills, and interpersonal communication skills. The Pearson
      analysis revealed significantly positive correlations between communication
      abilities and the students' educational level, clinical training experience,
      living circumstances and number of siblings. CONCLUSION: Most nursing students
      need communication skill training. Multiple factors, including educational level,
      living circumstances, number of siblings, and training experience significantly
      affect nursing students' communication abilities. Our study suggested a need to
      widely establish a communication course or clinical communication training
      program to improve nursing students' communication skills.

PMID- 22417663
TI  - Can the fall in serum FSH during coasting in IVF/ICSI predict clinical outcomes?
AB  - This retrospective cohort study determined whether the total falls in serum FSH
      and oestradiol concentrations from start to end of coasting in
      IVF/intracytoplasmic sperm injection could predict clinical outcomes. Ninety-nine
      cycles, with gonadotrophin-releasing hormone-agonist down-regulation where
      coasting with serial serum oestradiol and FSH monitoring was adopted due to risk
      of severe ovarian hyperstimulation syndrome, were consecutively included. The
      primary clinical outcome was live-birth rate (LBR); other outcomes measured were
      number of oocytes retrieved and fertilization, implantation and clinical
      pregnancy rates. LBR for FSH fall>10 IU/l compared with 5-10 and<5 IU/l were
      45.4% versus 22.0% and 25.0%, respectively. Mean serum FSH fall was similar with
      and without live birth (8.4 +/- 6.2 versus 7.3 +/- 5.0 IU/l) as were mean
      oestradiol and FSH concentrations on HCG administration, oestradiol fall,
      percentage fall in FSH/oestradiol and duration of coasting. None of the variables
      efficiently predicted live birth on regression analysis. The AUC of FSH fall was
      0.53 at 11.0 IU/l. Basal FSH, starting and total gonadotrophin dose and duration
      of coasting were positively correlated with FSH fall. A potentially clinically
      important association between live birth and FSH fall during coasting was
      apparent, which requires further evaluation. The purpose of this retrospective
      cohort study was to determine whether the magnitude of fall in the serum FSH and
      oestradiol concentrations from start to end of coasting in IVF/intracytoplasmic
      sperm injection cycles could predict the clinical outcomes. Gonadotrophin
      releasing hormone-agonist down-regulated cycles (n=99), where coasting with
      serial serum oestradiol and FSH monitoring was adopted due to risk of ovarian
      hyperstimulation, were consecutively included. Live birth was the primary
      clinical outcome measured; number of oocytes retrieved and fertilization,
      implantation and clinical pregnancy rates were the other outcomes examined. Live
      birth rate tended to be high when FSH fall was >10 IU/l, compared with 5-10 IU/l
      and <5 IU/l, although not statistically significantly. Mean serum FSH fall were
      similar in live-birth and no-live-birth cycles (8.4 +/- 6.2 versus 7.3 +/- 5.0)
      as were mean oestradiol and FSH concentrations on hCG administration, oestradiol
      fall, percentage fall in FSH and oestradiol and duration of coasting. None of the
      variables efficiently predicted live birth. The area under the curve of FSH fall
      was 0.53. FSH fall of <11.0 IU/l was found to be more likely to predict negative
      outcome (specificity 84.72%) than predicting positive outcome when FSH fall was
      >11 IU/l (sensitivity 34.48%). Women's basal FSH, starting and total
      gonadotrophin dose of ovarian stimulation and duration of coasting had direct
      positive correlation with the magnitude of FSH fall. A potentially clinically
      important rise in live birth in association with greater FSH fall during coasting
      was apparent, which requires further evaluation.

PMID- 22417664
TI  - The benefit of artificial oocyte activation is dependent on the fertilization
      rate in a previous treatment cycle.
AB  - Following intracytoplasmic sperm injection (ICSI), some patients present low or
      zero fertilization rates. Artificial oocyte activation has been proposed as a
      suitable means to overcome this problem. This study applied artificial oocyte
      activation in patient cohorts with a history of no fertilization (0%, group 1),
      fertilization between 1 and 29% (group 2) or fertilization between 30 and 50%
      (group 3) in initial ICSI cycles. In the following treatment cycles, oocytes were
      activated after ICSI using calcium ionophore. Fertilization, pregnancy and take
      home baby rates were compared with the previous cycle without activation. In
      group 1, fertilization rate was 41.6%, embryos for transfer were available in
      82.1% of cycles, giving a clinical pregnancy rate of 18.8% and take-home baby
      rate of 12.8%. In group 2, despite a lower transfer rate (87.9% versus 100%,
      P<0.05), there were higher fertilization and clinical pregnancy rates (44.4%
      versus 19.3% and 31.4% versus 12.8%, respectively, P<0.05) and take-home baby
      rate was 24.1% versus 12.8%. In group 3, fertilization rates differed (56.1%
      versus 36.8%; P<0.001) but all other parameters were similar. Artificial oocyte
      activation has great potential especially in patients showing compromised
      fertilization rates below 30% after standard ICSI. Following intracytoplasmic
      sperm injection (ICSI), some patients present very low or even zero fertilization
      rates after ICSI. Artificial oocyte activation has been proposed as a suitable
      means to overcome this problem. We applied artificial oocyte activation in
      patients which presented a history either no fertilization, fertilization between
      0 and 30% or fertilization between 30 and 50% in initial ICSI cycles. In the
      following treatment cycles, oocytes were activated after ICSI using a calcium
      ionophore. Fertilization, pregnancy and take-home baby rates were compared to the
      previous cycle without activation. For the groups with previously 0% or 1-29%
      fertilization, we noted higher fertilization rates and clinical pregnancy rates
      per embryo transfer. For the group with moderate fertilization, only
      fertilization rates differed but all other parameters were not significantly
      different. From these data we conclude that artificial oocyte activation has a
      great potential especially in patients which show a compromised fertilization
      rate below 30% in a standard ICSI cycle.

PMID- 22417665
TI  - The eutopic endometrium in endometriosis: are the changes of clinical
      significance?
AB  - The eutopic endometrium in women suffering from endometriosis is different in
      many ways from that of healthy controls. Both proliferative and secretory eutopic
      endometria exhibit changes in endometriosis with heterogeneous responses. In
      addition, nerve fibres appear in the endometrium and myometrium of these women.
      The endometrium is a rich source of pro-angiogenic factors and vascular events
      are often disrupted in endometriosis with an overall increase in angiogenesis. A
      number of investigations have shown that endometriosis is likely the most common
      cause of endometrial receptivity defects. Endometriosis is also associated with
      relative 17beta-hydroxysteroid dehydrogenase type II deficiency and these
      molecular aberrations indicate that local oestrogen production sustains ectopic
      implants. Recently it has been shown that endometriosis, as a chronic
      inflammatory disorder, disrupts co-ordinated progesterone response throughout the
      reproductive tract, including the endometrium, leading to a condition of
      'progesterone resistance'. Investigators have searched for biomarkers of
      endometriosis, but these investigations are fraught with methodological
      difficulties. In conclusion, molecular phenotyping of the endometrium is changing
      the disease paradigm, from being foremost an oestrogen-dependent disease to a
      disorder characterized primarily by progesterone resistance. In recent years,
      research on the pathogenesis of endometriosis has been focused on alterations in
      the uterus and particularly the eutopic endometrium. The eutopic endometrium in
      women suffering from endometriosis is different in many ways from that of healthy
      controls. Both proliferative and secretory eutopic endometria exhibit changes in
      endometriosis with heterogeneous responses. The endometrium is a rich source of
      pro-angiogenic factors and vascular events are often disrupted in endometriosis
      with an overall increase in angiogenesis. A number of investigations have shown
      that endometriosis is likely the most common cause of endometrial receptivity
      defects. Recently, it has been shown that endometriosis, as a chronic
      inflammatory disorder, disrupts co-ordinated progesterone response throughout the
      reproductive tract, including the endometrium, leading to a condition of
      'progesterone resistance'. Investigators have searched for biomarkers of
      endometriosis, but these investigations are fraught with methodological
      difficulties. In conclusion, molecular phenotyping of the endometrium is changing
      the disease paradigm; from being foremost an oestrogen-dependent disease to a
      disorder characterized primarily by progesterone resistance.

PMID- 22417666
TI  - No clinical relevance of the height of fundal indentation in subseptate or
      arcuate uterus: a prospective study.
AB  - The American Fertility Society has classified the arcuate uterus as a minor
      malformation with a benign clinical behaviour. The aim of this prospective study
      was to verify whether there is any scientific basis for this differentiation.
      Patients with at least one early miscarriage and a subseptate or arcuate uterus
      were admitted for hysteroscopic metroplasty. Patients were allocated to a
      subseptate uterus group, with an indentation of 1.5 cm or more, or an arcuate
      uterus group, with a smaller indentation. The miscarriage rates after metroplasty
      were similar between the two groups (14.0% in the subseptate uterus group versus
      11.1% in the arcuate uterus group). Before metroplasty, the miscarriage rates
      were significantly higher in subseptate uterus group, as well as in the arcuate
      uterus group (both P<0.001). According to these results, there is no evidence to
      support that the arcuate uterus has a different effect on the reproductive
      outcome in comparison to the subseptate uterus, neither before nor after surgical
      correction of the anomaly. Since there is no scientific basis for a separate
      classification of the arcuate uterus, a review of the classifications of uterine
      congenital anomalies should be considered as necessary. Congenital uterine
      malformations have been classified by the American Fertility Society (AFS) since
      1988. Although the AFS classification received wide acceptance and is still the
      most broadly used system, it is associated with various limitations in effective
      categorization of the anomalies. It is interesting that, until now, none of the
      other available options have been able to effectively replace the AFS system.
      Numerous papers indicate septate or subseptate (partial septate) uterus (AFS
      class V) is a possible cause of an unfavourable pregnancy outcome. Arcuate uterus
      (AFS class VI), a slight malformation similar to septate uterus, should differ
      from septate or subseptate uterus, because this 'minor' malformation should
      behave benignly with respect to the septate uterus. The aim of this study was to
      scientifically validate the difference between the arcuate and subseptate uterus
      in their effect on reproductive outcome through the results of a metroplasty in
      both groups of patients. A group of 96 patients, who underwent metroplasty after
      at least one early miscarriage, was divided into two groups according to the
      severity of the congenital uterine malformation. Our results indicate that there
      are no differences in pregnancy outcome after metroplasty either in patients with
      septate or arcuate utera. The poor pregnancy outcome in women with septate uterus
      seems not to be correlated to the dimension of the septum itself. There are no
      scientific bases for a separate classification of the arcuate uterus and it is
      proposed that a review of the classification of uterine congenital anomalies is
      necessary.

PMID- 22417667
TI  - Effect of HCG-day serum progesterone and oestradiol concentrations on pregnancy
      outcomes in GnRH agonist cycles.
AB  - This study analysed the relationship between serum progesterone/oestradiol
      concentrations and IVF pregnancy outcomes in gonadotrophin-releasing hormone
      agonist protocols. A total of 2921 infertile women undergoing IVF were assigned
      to four groups according to serum progesterone and oestradiol concentrations on
      the day of human chorionic gonadotrophin (HCG) administration: group 1 (control)
      progesterone<3.34 nmol/l and oestradiol<19,124 pmol/l; group 2 (high oestradiol);
      group 3 (high progesterone); group 4 (high progesterone and high oestradiol).
      Compared with group 1, group 4 had lower clinical pregnancy and live birth rates
      as well as the highest ectopic pregnancy rate (29.15% versus 45.91%; 18.67%
      versus 34.34%; 18.10% versus 5.82%; P<0.05). Group 3 had lower clinical pregnancy
      and live birth rates per embryo-transfer cycle (29.78% versus 45.91%; 20.28%
      versus 34.34%, respectively; P<0.05). Clinical pregnancy rates were similar in
      frozen-thawed embryo transfers (FET) among the four groups. In conclusion,
      elevated progesterone was detrimental to live birth rates. High serum oestradiol
      concentration on HCG day did not affect the IVF pregnancy outcome. In combination
      with the elevated progesterone, high oestradiol concentrations had a potential
      negative effect. For these patients, FET should be suggested to improve the
      pregnancy outcomes. The aim of this study was to analyse the relationship between
      serum progesterone/oestradiol concentrations and IVF pregnancy outcomes in
      gonadotrophin-releasing hormone agonist protocols. A total of 2921 infertile
      women undergoing IVF were assigned to four groups according to their serum
      progesterone and oestradiol concentrations on the day of human chorionic
      gonadotrophin (HCG) administration: group 1 (control) progesterone<3.34 nmol/l
      and oestradiol<19,124 pmol/l; group 2 (high oestradiol); group 3 (high
      progesterone); group 4 (high progesterone and high oestradiol). Compared with
      group 1, patients in group 4 had lower clinical pregnancy (29.15% versus 45.91%)
      and live birth rates (18.67% versus 34.34%) as well as the highest ectopic
      pregnancy rate (18.1% versus 5.82%) (all P<0.05). Those in group 3 had lower
      clinical pregnancy and live birth rates per embryo transfer cycle (29.78% versus
      45.91%; 20.28% versus 34.34%, respectively, P<0.05). Embryo quality appeared to
      be unaffected since similar clinical pregnancy rates in frozen-thawed embryo
      transfer (FET) cycles among the four groups. In conclusion, elevated progesterone
      was detrimental to live birth rates. A high serum oestradiol concentration on the
      day of HCG administration did not affect the IVF pregnancy outcome. In
      combination with the elevated progesterone and oestradiol concentrations had a
      potential negative effect. For these patients, FET should be suggested to improve
      the pregnancy outcomes.

PMID- 22417668
TI  - Expression and localization of opioid receptors during the maturation of human
      oocytes.
AB  - The endogenous opioid system has been characterized in some female reproductive
      organs, but little is known about the expression of these receptors in human
      oocytes. This study investigated the presence and differential distribution of
      the opioid receptors during the maturation of human oocytes. A total of 821 human
      oocytes from an intracytoplasmic sperm injection (ICSI) programme were studied
      including 213 at germinal-vesicle (GV) stage and 164 at metaphase-I (MI) stage
      and 444 failed fertilization metaphase-II (MII) oocytes. Additionally 31 MII
      oocytes corresponding to cases where ICSI was not attempted and 50 failed
      fertilization MII oocytes from the IVF programme were included. Western blot
      analysis revealed the presence of the delta (OPRD1), kappa (OPRK1) and mu (OPRM1)
      opioid receptors in human oocytes. The OPRK1 and OPRM1 immunostaining patterns
      changed during the maturation of the oocyte, while the OPRD1 pattern was the same
      throughout. In particular, OPRD1 were detected in peripheral tissue from the GV
      to the MII stage. OPRK1 were found peripherally at the GV stage, more internally
      at MI and homogeneously at MII. Finally, OPRM1 were located peripherally at the
      GV stage and homogeneously in MI and MII oocytes. Opioids may have a role in
      oocyte maturation, acting via receptors. The opioid system has been well
      characterized in the central nervous system, but it is now known that opioids
      also act in reproductive organs. However, little is known about the presence and
      function of this system in human oocytes and its role in their maturation. In
      this study, we investigated the presence and differential distribution of three
      (delta, kappa and mu) opioid receptors (proteins which bind the opioids) during
      the maturation of human oocytes. A total of 821 human oocytes (from 253 patients)
      not suitable for intracytoplasmic sperm injection (ICSI) or which did not develop
      into an embryo after ICSI were studied. Thus, we have verified the presence of
      the delta, kappa and mu opioid receptors in human oocytes. The kappa and mu
      localization changed during the maturation of the oocyte, while the Delta
      localization was the same throughout. In particular, the delta receptor was
      detected in the periphery of the oocyte. On the other hand, the kappa receptor
      was found peripherally at the beginning, more internally during maturation and
      homogeneously at the end of maturation. Finally, the Mu receptor was located
      peripherally at the beginning of maturation and homogeneously in the rest of the
      maturation stages. This finding suggests a possible role for opioids, acting via
      receptors, in the maturation of the oocyte.

PMID- 22417669
TI  - Anti-Mullerian hormone for the assessment of ovarian response in GnRH-antagonist
      treated oocyte donors.
AB  - Evidence regarding the role of anti-Mullerian hormone (AMH) among oocyte donors
      is limited and only involves gonadotrophin-releasing hormone (GnRH)-agonist
      treated donors. This trial assessed the predictive ability of AMH for ovarian
      response among 108 oocyte donors treated with an antagonist protocol. In
      multivariate linear regression analysis, both AMH and age were independently
      associated with ovarian response (unstandardized coefficients 0.904 and -0.378,
      respectively). In receiver operating characteristic curve analysis, AMH performed
      better than age, but was a modest predictive marker for low (<= 6 oocytes) and
      excessive (>20 oocytes) ovarian response (area under the curve (AUC) 0.643 and
      0.695, respectively). Similarly, a multivariate logistic model including AMH and
      age was also modest (AUC 0.651 and 0.697 for low and excessive responders,
      respectively). The predictive ability of AMH did not significantly alter when
      different thresholds were adopted, such as <4 oocytes for low response and >25
      for excessive response (AUC 0.759 and 0.724, respectively). Among oocyte donors
      treated with a GnRH-antagonist protocol, although AMH was correlated with the
      number of oocytes retrieved, it demonstrates a modest ability in discriminating
      women with low or excessive ovarian response. Selection of oocyte donors is of
      paramount importance for the proper and more cost-efficient functionality of the
      oocyte donation programme. Despite the extensive literature regarding the
      efficacy of anti-Mullerian hormone (AMH) for predicting ovarian response among
      infertile patients, available evidence regarding the role of AMH in oocyte donors
      is considerably limited and involves only agonist down-regulated cycles. In this
      trial we assessed whether AMH can be considered a predictive marker for ovarian
      response among oocyte donors treated with a gonadotrophin-releasing hormone
      (GnRH)-antagonist protocol. According to our results, among oocyte donors treated
      with a GnRH-antagonist protocol, although AMH was correlated with the number of
      oocytes retrieved, the correlation is not strong and it appears that AMH has a
      modest predictive ability to discriminate women who are likely to demonstrate
      either impaired or excessive response to ovarian stimulation.

PMID- 22417670
TI  - TNFalpha modulates protein degradation pathways in rheumatoid arthritis synovial
      fibroblasts.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive
      disease of the joint. The synovial lining consists of two main types of cells:
      synovial fibroblasts and macrophages. The macrophage-derived cytokine TNFalpha
      stimulates RA synovial fibroblasts to proliferate and produce growth factors,
      chemokines, proteinases and adhesion molecules, making them key players in the RA
      disease process. If proteins are not correctly folded, cellular stress occurs
      that can be relieved in part by increased degradation of the aberrant proteins by
      the proteasome or autophagy. We hypothesized that the activity of the protein
      degradation pathways would be increased in response to TNFalpha stimulation in RA
      synovial fibroblasts compared with control fibroblasts. METHODS: Endoplasmic
      reticulum (ER) stress markers were examined in synovial fibroblasts by
      immunoblotting and PCR. Use of the autophagy and proteasome protein degradation
      pathways in response to TNFalpha stimulation was determined using a combination
      of experiments involving chemical inhibition of the autophagy or proteasome
      pathways followed by immunoblotting for the autophagy marker LC3, measurement of
      proteasome activity and long-lived protein degradation, and determination of
      cellular viability. RESULTS: RA synovial fibroblasts are under acute ER stress,
      and the stress is increased in the presence of TNFalpha. Autophagy is the main
      pathway used to relieve the ER stress in unstimulated fibroblasts, and both
      autophagy and the proteasome are more active in RA synovial fibroblasts compared
      with control fibroblasts. In response to TNFalpha, the autophagy pathway but not
      the proteasome is consistently stimulated, yet there is an increased dependence
      on the proteasome for cell viability. If autophagy is blocked in the presence of
      TNFalpha, an increase in proteasome activity occurs in RA synovial fibroblasts
      but not in control cells. CONCLUSIONS: TNFalpha stimulation of synovial
      fibroblasts results in increased expression of ER stress markers. Survival of
      synovial fibroblasts is dependent on continuous removal of proteins by both the
      lysosome/autophagy and ubiquitin/proteasome protein degradation pathways. Both
      pathways are more active in RA synovial fibroblasts compared with control
      fibroblasts. These results may provide a better understanding of the mechanism of
      TNFalpha on prolonging the survival of synovial fibroblasts in RA tissue.

PMID- 22417671
TI  - Evaluation of a suicide prevention training curriculum for substance abuse
      treatment providers based on Treatment Improvement Protocol Number 50.
AB  - Substance use disorders (SUDs) confer risk for suicide yet there are no
      empirically supported suicide prevention training curricula tailored to SUD
      treatment providers. We assessed the efficacy of a 2-hour training that featured
      a suicide prevention training video produced by the Department of Veterans
      Affairs. The video was based on Treatment Improvement Protocol Number 50 (TIP 50)
      a practical manual to manage suicide risk produced by the Substance Abuse and
      Mental Health Services Administration. The training was provided in small groups
      to 273 SUD treatment providers in 18 states. Results were evaluated using self
      report assessments obtained at pre-test, post-test, and 2-month follow-up.
      Statistically significant changes (p < .001) within subjects were obtained on
      self-efficacy, knowledge, and frequency of suicide prevention practice behaviors.
      The positive results together with the brevity of the training and its ease of
      implementation indicate high potential for widespread adoption and the importance
      of further study.

PMID- 22417672
TI  - Young people and caregivers' perceptions of an intervention program for children
      who deliberately light fires.
AB  - A significant number of children and adolescents engage in deliberate fire
      setting, beyond the scope of curiosity and experimentation. Interventions
      developed to respond to the needs of such fire setters generally involve
      educational and/or psychosocial approaches. Research evaluating the effectiveness
      of these interventions is dominated by outcome studies which rely on recidivism
      rates determined by either official records or parent reports. There has however,
      been no process evaluation studies published. This study presents a process
      analysis which aimed to identify the strengths and weaknesses of a Fire Awareness
      and Intervention Program in New Zealand, from the perspectives of program
      consumers. Qualitative research methods were employed, with data being derived
      from in-depth interviews with young people and their parents/caregivers. The
      analysis indicated that (a) the FAIP was generally regarded as a positive
      experience, (b) practitioners' qualities of empathy and understanding are
      important for developing rapport with the young people and their parents, (c)
      education-based intervention tailored to the young person's age and developmental
      level is important, (d) educational resources need to be updated and used
      flexibly to respond appropriately to the age and developmental level of the young
      person, and (e) inter-agency and intra-agency relationships need to be developed
      and maintained, with formal arrangements for reciprocal referral systems
      developed in order to respond to the needs of the clients. The resulting
      implications for service providers, along with future research are discussed.

PMID- 22417673
TI  - Conducting a Hispanic Health Needs Assessment in rural Kansas: building the
      foundation for community action.
AB  - Healthy People 2020 states ethnic health disparities are a priority for the US.
      Although considerable national statistics document ethnic-related health
      disparities, information specific to rural areas is scarce and does not provide
      direction for implementing chronic disease prevention programming. Therefore, the
      purpose of our project was to use the Hispanic Health Needs Assessment (HHNA), a
      tool designed by the National Alliance for Hispanic Health (NAHH), in culturally
      diverse, rural Southwest Kansas. Our focus areas included: access to healthcare,
      heart disease, diabetes, overweight, nutrition, and physical activity. METHODS:
      The assessment followed six steps: (1) developing the assessment team, (2) data
      gathering using community member surveys, existing statistics and community
      leader interviews, (3) assembling the findings, (4) formulating recommendations
      for action at individual, institutional, community and policy levels, (5) sharing
      findings and program planning, and (6) sharing findings with NAHH. We identified
      several challenges collecting health related data in rural communities, but
      overall, the HHNA was a comprehensive and useful tool for guiding a community
      level health assessment. CONCLUSION: This process has provided our community
      partners with locally relevant statistics regarding the current status of health,
      health behaviors, and perceived community needs to inform resource allocation,
      program planning and applications for new funding initiatives.

PMID- 22417674
TI  - Automated high-throughput Vibrio fischeri assay for (eco)toxicity screening:
      application to ionic liquids.
AB  - An automated high-throughput Vibrio fischeri assay was developed and further
      applied to the evaluation of ionic liquids (ILs) (eco)toxicity. The assay was
      based on the reduction of bacterial bioluminescence in the presence of test
      compounds and the results were presented as EC(50). The assays were performed
      with eight commercially available ILs with distinct cationic head groups, alkyl
      side chains and anions. EC(50) values between 6.5 and 691.9 mmol L(-1) were
      obtained for the tested ILs, being hmim [Cl] the most toxic and bmim [Cl] the
      less toxic ones, confirming the influence of the different structural elements.
      Moreover, all the tested ILs exhibited a (eco)toxicity lower than Cu(II), used as
      a positive control during the optimization and analysis steps. The automated
      assay assured the precise control of the contact time between V. fischeri and
      test compound by means of a simple protocol that guaranteed adequate aspiration
      and handling of the solutions as well as the precise implementation of a computer
      controlled stop period. Furthermore, a significant reduction of the assay costs
      was achieved through automation mainly by a drastic reduction of the volume of
      bacterial suspension and test compound. The methodology was validated by
      comparison with a microplate assay; it was stated that the results, obtained
      after a 3min contact time, changed proportionally relatively to Cu(II) in both
      assays. This confirmed the applicability of the methodology as an (eco)toxicity
      screening assay, with reduction of time and increase of robustness and
      repeatability (n=10; rsd<1.1%). It is expected that due to its simplicity and
      reduced cost the developed assay can be integrated in the early stage of
      development of new compounds as a rapid screening test.

PMID- 22417675
TI  - Linking embryo toxicity with genotoxic responses in the freshwater snail Physa
      acuta: single exposure to benzo(a)pyrene, fluoxetine, bisphenol A, vinclozolin
      and exposure to binary mixtures with benzo(a)pyrene.
AB  - Genotoxic effects on fauna after waterborne pollutant exposure have been
      demonstrated by numerous research programmes. Less effort has been focused on
      establishing relationship between genotoxicity and long-term responses at higher
      levels of biological organization. Taking into account that embryos may be more
      sensitive indicators of reproductive impairment than alterations in fertility, we
      have developed two assays in multiwell plates to address correlations between
      embryo toxicity and genotoxicity. The potential teratogenicity was assessed by
      analyzing abnormal development and mortality of Physa acuta at embryonic stage.
      Genotoxicity was measured by the micronucleus (MN) test using embryonic cells.
      Our results showed that linkage between genotoxicity and embryo toxicity depends
      on mechanisms of action of compounds under study. Embryo toxic responses showed a
      clear dose-related tendency whereas no clear dose-dependent effect was observed
      in micronucleus induction. The higher embryo toxicity was produced by
      benzo(a)pyrene exposure followed by fluoxetine and bisphenol A. Vinclozolin was
      the lower embryo toxic compound. Binary mixtures with BaP always resulted in
      higher embryo toxicity than single exposures but antagonistic effects were
      observed for MN induction. Benzo(a)pyrene produced the higher MN induction at
      0.04 mg/L, which also produced clear embryo toxic effects. Fluoxetine did not
      induce cytogenetic effects but 0.25mg/L altered embryonic development. Bisphenol
      A significantly reduced hatchability at 0.5mg/L while MN induction appeared with
      higher treatments than those that start causing teratogenicity. Much higher
      concentration of vinclozolin (5mg/L) reduced hatchability and induced maximum MN
      formation. In conclusion, while validating one biomarker of genotoxicity and
      employing one ecologically relevant effect, we have evaluated the relative
      sensitivity of a freshwater mollusc for a range of chemicals. The embryo toxicity
      test is a starting point for the development of a life cycle test with freshwater
      snails even for undertaking multigeneration studies focused on transgenerational
      effects.

PMID- 22417676
TI  - Isolation and identification of phosphate solubilizing bacteria able to enhance
      the growth and aloin-A biosynthesis of Aloe barbadensis Miller.
AB  - The effect of four phosphate solubilizing bacteria (PSB) was studied on growth
      and aloin-A content of Aloe barbadensis in soil containing tricalcium phosphate
      (TCP). PSB were identified based on 16S rRNA gene sequencing as Pseudomonas
      synxantha, Burkholderia gladioli, Enterobacter hormaechei and Serratia
      marcescens. These PSB solubilized 25-340 MUg ml(-1) of TCP into the liquid phase.
      The treatment of plants with individual PSB or mixture of these increased soil
      available P, P uptake in plants and plant growth. The increase in aloin-A content
      due to higher plant biomass and unit biomass production was 673%, 294%, 276%,
      119% and 108% in plants treated with a PSB consortium, P. synxantha, S.
      marcescens, B. gladioli, and E. hormaechei in TCP amended soil, respectively.

PMID- 22417677
TI  - Disease-related malnutrition in outpatients with systemic sclerosis.
AB  - BACKGROUND & AIM: Disease-related malnutrition is known to negatively affect
      clinical outcomes. The aim of the present study was to evaluate the prevalence of
      malnutrition in a cohort of outpatients affected by Systemic Sclerosis (SSc) and
      its association with clinical variables. METHODS: One hundred sixty SSc patients
      were consecutively evaluated. The following clinical variables were assessed:
      disease duration, activity and severity, treatments, functional status,
      gastrointestinal involvement. Nutritional assessment included: body mass index
      (BMI), weight loss (WL) history, nutritional intakes and serum prealbumin.
      Malnutrition was defined as BMI <20 kg/m2 and/or previous 6-month WL >= 10%.
      RESULTS: Prevalence of malnutrition was 15% (10-21%). Logistic regression showed
      that malnutrition was independently associated with disease activity (OR 3.72; p
      < 0.001) and low serum prealbumin (OR 8.58; p < 0.001). The association with
      gastrointestinal involvement was not statistically significant, although a trend
      was detected (OR 1.88). CONCLUSION: Malnutrition is common in SSc outpatients. It
      appears associated with disease activity and not influenced by nutritional
      intakes; gastrointestinal involvement might contribute to its development over
      time. Serum prealbumin could be an early marker of malnutrition in SSc, whose
      role should be confirmed by further longitudinal investigations. Prospective
      studies are also required to clarify the clinical significance of the association
      between malnutrition and disease activity in SSc.

PMID- 22417678
TI  - Structural assessment of nanocomposites.
AB  - This paper provides an overview on structural assessment of nanocomposite
      materials. First of all, a brief description of advanced structure
      characterization methods such as scanning electron microscopy, X-ray diffraction,
      transmission electron microscopy, atomic force microscopy, and scanning tunneling
      microscopy is presented. Secondly, applications of these methods for analysis of
      structures and compositions of typical nanocomposites are introduced. The
      nanocomposites are formed by different nanoscale processing technologies.
      Electrochemically polymerized polyaniline (PANi) nanocomposites,
      thermomechanically processed metal matrix nanocomposites, nanocast ceramic matrix
      composites are typical examples discussed in this paper. Case studies on several
      functional nanocomposites for energy storage/conversion, catalysis and sensing
      applications are mentioned. After that, assessment of the interface structures of
      nanocomposite materials using surface characterization techniques and mechanical
      damage models is discussed. Finally, concluding remarks are provided.

PMID- 22417679
TI  - Early outcome following diathermy versus cold knife ablation of posterior
      urethral valves.
AB  - OBJECTIVE: To compare early outcomes following diathermy versus cold knife
      ablation of posterior urethral valves (PUV). METHODS: All neonates and children
      who underwent primary ablation of PUV between January 2004 and March 2011 were
      included. Primary ablation was performed using an 8.5 resectoscope, with either
      diathermy hook (Group I) or sickle-shaped cold knife (Group II). A uniform
      management protocol was used and voiding cystourethrogram was repeated in all
      patients at 3 months follow-up. All patients with poor anterior urethral stream
      and persistent dilatation of posterior urethra on follow-up underwent repeat
      cystoscopy. Early outcomes were compared between Groups I and II using Fisher's
      exact test. RESULTS: During the study period, a total of 83 cases underwent
      primary PUV ablation. Group I included 42 patients (mean age 6.2 months; 10 days
      to 9 years) while Group II included 41 (mean age 3.4 months; 12 days to 5 years).
      Overall 12/83 (14.4%) required repeat procedure for persistent obstruction:
      stricture 9 (10.8%); residual valve 3 (3.6%). Group I had a significantly higher
      stricture rate (9/42; 21.4%) than Group II (0/41) (p = 0.02). There was no
      significant difference in terms of residual valves, haematuria, retention or
      extravasation between groups. CONCLUSION: Cold knife ablation is superior to
      diathermy in relieving PUV obstruction in a single attempt.

PMID- 22417680
TI  - Transumbilical laparoendoscopic single-site gonadectomy for Turner's syndrome
      with Y-chromosome mosaicism.
AB  - Laparoendoscopic single-site surgery (LESS), a minimally invasive procedure, is
      gaining widespread acknowledgment in pediatric urology. We report the case of a 7
      year-old girl with Turner's syndrome with 45,XO/46,XY mosaicism, for whom
      bilateral prophylactic gonadectomy using LESS was performed. Histopathological
      findings revealed bilateral streak gonads. The surgical and cosmetic outcome was
      excellent. Diagnostic and therapeutic laparoscopy is essential for accurate
      clinical management of patients with disorders of sex development. Although this
      is only a single case report, it supports the theory that LESS is an exceedingly
      practical and superior technique for such children, since it provides excellent
      magnification, as well as allowing normal psychological development owing to the
      concealed scar. Further studies and long-term follow-up are required to evaluate
      the benefits and limitations of applying LESS in pediatrics.

PMID- 22417681
TI  - Dose-escalating study of the pharmacokinetics and tolerability of fesoterodine in
      children with overactive bladder.
AB  - OBJECTIVE: To determine the pharmacokinetics, safety and tolerability of
      fesoterodine, and assess the utility of 3-day bladder diaries (exploratory
      objective) in pediatric subjects with neurogenic detrusor overactivity or
      idiopathic overactive bladder (OAB). METHODS: In this 8-week open-label study,
      subjects (8-17 years, >25 kg) received fesoterodine 4 mg for 4 weeks, then 8 mg
      for 4 weeks. Blood samples were obtained at weeks 4 and 8. RESULTS: Of 21
      subjects enrolled, 11 had neurogenic detrusor overactivity and 10 had idiopathic
      OAB; 1 discontinued (personal reasons). Mean age and weight were 13.2 years and
      54.0 kg for boys (n = 12) and 13.1 years and 49.2 kg for girls (n = 9). 5-Hydroxy
      methyltolterodine plasma concentrations did not differ by diagnosis and were
      consistent with predictions based on adult data. Treatment-related adverse events
      (all mild or moderate) included 1 event each of dry mouth, constipation, dry eyes
      and blurred vision, and 2 events each of nausea and increased post-void residual
      volume. Three-day bladder diaries proved feasible. CONCLUSIONS: Oral
      administration of fesoterodine in pediatric subjects (>25 kg) with idiopathic OAB
      or neurogenic detrusor overactivity produced steady-state plasma 5-hydroxy
      methyltolterodine exposures similar to those in adults. The doses given were well
      tolerated.

PMID- 22417682
TI  - Genetic analysis of precore/core and partial pol genes in an unprecedented
      outbreak of fulminant hepatitis B in India.
AB  - We investigated an unprecedented outbreak of fulminant hepatitis B virus (HBV)
      that occurred in Modasa, Gujarat (India) in 2009. Genomic analysis of all
      fulminant hepatic failure cases confirmed exclusive predominance of subgenotype
      D1. A1762T, G1764A basal core promoter (BCP) mutations, insertion of isoleucine
      after nt 1843, stop codon mutation G1896A, G1862T transversion plus seven other
      mutations in the core gene caused inhibition of HBeAg expression implicating them
      as circulating precore/BCP mutant virus. Two rare mutations at amino acids 89
      (Ile->Ala) and 119 (Leu->Ser) in addition to other mutations in the polymerase
      (pol) gene may have caused some alteration in either of four pol gene domains to
      affect encapsidation of pregenomic RNA to enhance pathogenicity. Sequence
      similarity among patients' sequences suggested an involvement of a single
      hepatitis B mutant strain/source to corroborate the finding of gross and
      continued usage of HBV mutant-contaminated syringes/needles by a physician which
      resulted in this unprecedented outbreak of fulminant hepatitis B. The fulminant
      exacerbation of the disease might be attributed to mutations in the
      BCP/precore/core and pol genes that may have occurred due to selection pressure
      during rapid spread/mutation of the virus.

PMID- 22417683
TI  - Host cell deformability is linked to transmission in the human malaria parasite
      Plasmodium falciparum.
AB  - Gametocyte maturation in Plasmodium falciparum is a critical step in the
      transmission of malaria. While the majority of parasites proliferate asexually in
      red blood cells, a small fraction of parasites undergo sexual conversion and
      mature over 2 weeks to become competent for transmission to a mosquito vector.
      Immature gametocytes sequester in deep tissues while mature stages must be able
      to circulate, pass the spleen and present themselves to the mosquito vector in
      order to complete transmission. Sequestration of asexual red blood cell stage
      parasites has been investigated in great detail. These studies have demonstrated
      that induction of cytoadherence properties through specific receptor-ligand
      interactions coincides with a significant increase in host cell stiffness. In
      contrast, the adherence and biophysical properties of gametocyte-infected red
      blood cells have not been studied systematically. Utilizing a transgenic line for
      3D live imaging, in vitro capillary assays and 3D finite element whole cell
      modelling, we studied the role of cellular deformability in determining the
      circulatory characteristics of gametocytes. Our analysis shows that the red blood
      cell deformability of immature gametocytes displays an overall decrease followed
      by rapid restoration in mature gametocytes. Intriguingly, simulations suggest
      that along with deformability variations, the morphological changes of the
      parasite may play an important role in tissue distribution in vivo. Taken
      together, we present a model, which suggests that mature but not immature
      gametocytes circulate in the peripheral blood for uptake in the mosquito blood
      meal and transmission to another human host thus ensuring long-term survival of
      the parasite.

PMID- 22417685
TI  - Physiochemical properties of alkylaminium sulfates: hygroscopicity,
      thermostability, and density.
AB  - Although heterogeneous interaction of amines has been recently shown to play an
      important role in the formation and growth of atmospheric aerosols, little
      information is available on the physicochemical properties of aminium sulfates.
      In this study, the hygroscopicity, thermostability, and density of alkylaminium
      sulfates (AASs) have been measured by an integrated aerosol analytical system
      including a tandem differential mobility analyzer and an aerosol particle mass
      analyzer. AAS aerosols exhibit monotonic size growth at increasing RH without a
      well-defined deliquescence point. Mixing of ammonium sulfate (AS) with AASs
      lowers the deliquescence point corresponding to AS. Particles with AASs show
      comparable or higher thermostability than that of AS. The density of AASs is
      determined to be 1.2-1.5 g cm(-3), and an empirical model is developed to predict
      the density of AASs on the basis of the mole ratio of alkyl carbons to total
      sulfate. Our results reveal that the heterogeneous uptake of amines on sulfate
      particles may considerably alter the aerosol properties. In particular, the
      displacement reaction of alkylamines with ammonium sulfate aerosols leads to a
      transition from the crystalline to an amorphorous phase and an improved water
      uptake, considerably enhancing their direct and indirect climate forcing.

PMID- 22417684
TI  - Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import
      able to inhibit replication of HIV-1 and dengue virus.
AB  - The movement of proteins between the cytoplasm and nucleus mediated by the
      importin superfamily of proteins is essential to many cellular processes,
      including differentiation and development, and is critical to disease states such
      as viral disease and oncogenesis. We recently developed a high-throughput screen
      to identify specific and general inhibitors of protein nuclear import, from which
      ivermectin was identified as a potential inhibitor of importin alpha/beta
      mediated transport. In the present study, we characterized in detail the nuclear
      transport inhibitory properties of ivermectin, demonstrating that it is a broad
      spectrum inhibitor of importin alpha/beta nuclear import, with no effect on a
      range of other nuclear import pathways, including that mediated by importin beta1
      alone. Importantly, we establish for the first time that ivermectin has potent
      antiviral activity towards both HIV-1 and dengue virus, both of which are
      strongly reliant on importin alpha/beta nuclear import, with respect to the HIV-1
      integrase and NS5 (non-structural protein 5) polymerase proteins respectively.
      Ivermectin would appear to be an invaluable tool for the study of protein nuclear
      import, as well as the basis for future development of antiviral agents.

PMID- 22417686
TI  - Import and efflux of flubendazole in Haemonchus contortus strains susceptible and
      resistant to anthelmintics.
AB  - Drug entry into the body of a helminth is a key factor in the efficacy of
      anthelmintics. The present project was designed to study the ex vivo uptake and
      efflux of the benzimidazole anthelmintic flubendazole (FLU) in four strains of H.
      contortus: the ISE strain (fully susceptible to anthelmintics), the ISE-S strain
      (resistant to ivermectin), the BR strain (resistant to benzimidazoles) and the WR
      strain (multi-resistant). The transport of FLU between dead and living nematodes
      was also compared as well as the effect of verapamil, an inhibitor of the main
      efflux ABCB1 transporter (P-glycoprotein), on FLU accumulation in nematodes. The
      obtained results showed that FLU is able to effectively enter H. contortus adults
      due to high FLU lipophilicity. Passive diffusion is probably the only mechanism
      in both FLU import and efflux from nematodes. No differences in FLU transport
      were found among four H. contortus strains with different sensitivity to
      anthelmintics. No active FLU efflux from H. contortus and no effect of verapamil
      were observed, indicating that H. contortus cannot protect itself against FLU by
      the active removal of this anthelmintic from its body.

PMID- 22417687
TI  - Clinical features of symptomatic patellofemoral joint osteoarthritis.
AB  - INTRODUCTION: Patellofemoral joint osteoarthritis (OA) is common and leads to
      pain and disability. However, current classification criteria do not distinguish
      between patellofemoral and tibiofemoral joint OA. The objective of this study was
      to provide empirical evidence of the clinical features of patellofemoral joint OA
      (PFJOA) and to explore the potential for making a confident clinical diagnosis in
      the community setting. METHODS: This was a population-based cross-sectional study
      of 745 adults aged >= 50 years with knee pain. Information on risk factors and
      clinical signs and symptoms was gathered by a self-complete questionnaire, and
      standardised clinical interview and examination. Three radiographic views of the
      knee were obtained (weight-bearing semi-flexed posteroanterior, supine skyline
      and lateral) and individuals were classified into four subsets (no radiographic
      OA, isolated PFJOA, isolated tibiofemoral joint OA, combined
      patellofemoral/tibiofemoral joint OA) according to two different cut-offs: 'any
      OA' and 'moderate to severe OA'. A series of binary logistic and multinomial
      regression functions were performed to compare the clinical features of each
      subset and their ability in combination to discriminate PFJOA from other subsets.
      RESULTS: Distinctive clinical features of moderate to severe isolated PFJOA
      included a history of dramatic swelling, valgus deformity, markedly reduced
      quadriceps strength, and pain on patellofemoral joint compression. Mild isolated
      PFJOA was barely distinguished from no radiographic OA (AUC 0.71, 95% CI 0.66,
      0.76) with only difficulty descending stairs and coarse crepitus marginally
      informative over age, sex and body mass index. Other cardinal signs of knee OA -
      the presence of effusion, bony enlargement, reduced flexion range of movement,
      mediolateral instability and varus deformity - were indicators of tibiofemoral
      joint OA. CONCLUSIONS: Early isolated PFJOA is clinically manifest in symptoms
      and self-reported functional limitation but has fewer clear clinical signs. More
      advanced disease is indicated by a small number of simple-to-assess signs and the
      relative absence of classic signs of knee OA, which are predominantly
      manifestations of tibiofemoral joint OA. Confident diagnosis of even more
      advanced PFJOA may be limited in the community setting.

PMID- 22417688
TI  - Refractory disseminated pyoderma gangrenosum, with dependence on corticosteroids,
      responding to potassium iodide.

PMID- 22417689
TI  - Rosai-Dorfman disease of the lung.

PMID- 22417690
TI  - Dermatological diseases in lizards.
AB  - Lizards with dermatological disease are routinely encountered in veterinary
      practice and it is often challenging to establish a thorough and adequate case
      management for these otherwise highly visible conditions. Most skin diseases in
      lizards are primarily a consequence of environmental stressors such as
      substandard husbandry and underlying disease, facilitating the onset of mainly
      secondary bacterial and mycotic dermal infections. This review provides an
      overview of common dermatological problems in lizards and aetiology, treatment
      and prevention are discussed for both infectious and non-infectious conditions.
      Although investigational approaches may be directed by the primary clinical
      manifestation of dermatological problems, the importance of a multidirectional
      approach cannot be over-emphasized. Proper treatment can only be initiated when
      the correct diagnosis has been made and husbandry issues dealt with. Current
      information on susceptibility patterns and on the use of appropriate
      chemotherapeutics in lizards is limited for the treatment of infectious causes of
      dermatitis.

PMID- 22417691
TI  - Rare case of left-dominant arrhythmogenic right ventricular cardiomyopathy with
      dramatic reverse remodeling after cardiac resynchronization as an adjunct to
      pharmacological therapy.
AB  - A 57-year-old man presented with near syncope and hemodynamic compromise after
      exercise. A sustained ventricular tachycardia (VT) of right bundle-branch block
      morphology was evident upon examination at our emergency department. Baseline 12
      lead electrocardiography revealed a sinus rhythm with a complete left bundle
      branch block after successful cardioversion of the VT. Coronary angiography
      revealed patent coronary arteries, whereas left ventriculography demonstrated
      impaired systolic function, accompanied by a peculiar basal lateral aneurysm.
      Both echocardiography and magnetic resonance imaging were consistent with a
      diagnosis of left-dominant arrhythmogenic right ventricular cardiomyopathy. Four
      months later, substantial ventricular reverse remodeling and clinical
      improvements were observed after cardiac resynchronization therapy with a
      defibrillator, as an adjunct to conventional pharmacological therapy.

PMID- 22417692
TI  - miR-Sens--a retroviral dual-luciferase reporter to detect microRNA activity in
      primary cells.
AB  - MicroRNA-mRNA interactions are commonly validated and deconstructed in cell lines
      transfected with luciferase reporters. However, due to cell type-specific
      variations in microRNA or RNA-binding protein abundance, such assays may not
      reliably reflect microRNA activity in other cell types that are less easily
      transfected. In order to measure miRNA activity in primary cells, we constructed
      miR-Sens, a MSCV-based retroviral vector that encodes both a Renilla luciferase
      reporter gene controlled by microRNA binding sites in its 3' UTR and a Firefly
      luciferase normalization gene. miR-Sens sensors can be efficiently transduced in
      primary cells such as human fibroblasts and mammary epithelial cells, and allow
      the detection of overexpressed and, more importantly, endogenous microRNAs.
      Notably, we find that the relative luciferase activity is correlated to the miRNA
      expression, allowing quantitative measurement of microRNA activity. We have
      subsequently validated the miR-Sens 3' UTR vectors with known human miRNA-372,
      miRNA-373, and miRNA-31 targets (LATS2 and TXNIP). Overall, we observe that miR
      Sens-based assays are highly reproducible, allowing detection of the independent
      contribution of multiple microRNAs to 3' UTR-mediated translational control of
      LATS2. In conclusion, miR-Sens is a new tool for the efficient study of microRNA
      activity in primary cells or panels of cell lines. This vector will not only be
      useful for studies on microRNA biology, but also more broadly on other factors
      influencing the translation of mRNAs.

PMID- 22417693
TI  - Rapid detection of methicillin-resistant Staphylococcus aureus in screening
      samples by relative quantification between the mecA gene and the SA442 gene.
AB  - Rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) is
      important to identify patients colonized with this pathogen and implement
      infection control precautions. We aimed to improve the combined use of the mecA
      gene polymerase chain reaction (PCR) and the SA442 PCR to detect MRSA in clinical
      screening samples. In a true MRSA the mecA copy number will be equal to the SA442
      copy number, whereas in samples with a methicillin-sensitive Staphylococcus
      aureus (MSSA) combined with a methicillin-resistant coagulase-negative
      Staphylococcus (MRCNS) the copy numbers will usually differ. Here we introduce a
      PCR system, relative quantification PCR (RQ-PCR), which takes this difference
      into account. RQ-PCR identifies true MRSA in clinical samples with a specificity
      that is comparable to the SCCmec-based PCRs.

PMID- 22417694
TI  - The examination of source distribution in a large sample by Monte Carlo
      simulation.
AB  - In this work, realistic Monte Carlo simulations were carried out for several
      distributions of activity in a waste drum to observe the dependence of the
      efficiency on the source distribution and to test whether the efficiency can be
      correlated with the shape of the spectra.

PMID- 22417695
TI  - Evaluation of rib microstructure in Wistar rats using SR-MUCT after radiation
      therapy simulation for breast cancer.
AB  - A better understanding of biological interactions that occur after exposure to
      photon radiation is needed in order to optimize therapeutic regimens and
      facilitate development and strategies that decrease radiation-induced side
      effects in humans. In this work, ribs of Wistar rat submitted to radiotherapy
      simulation were imaged using synchrotron radiation computed microtomography at
      Elettra Synchrotron Laboratory in Trieste, Italy. Histomorphometric parameters
      were calculated directly from the 3D microtomographic images and showed
      significant differences between irradiated and non-irradiated groups.

PMID- 22417696
TI  - Standardization of (166m)Ho and 243Am/239Np by live-timed anti-coincidence
      counting with extending dead time.
AB  - The National Laboratory for Metrology of Ionizing Radiation (LNMRI)/Brazil
      acquired (166m)Ho and (243)Am/(239)Np solutions from commercial suppliers in
      order to realize primary standardization and therefore reducing the associated
      uncertainties. The method used in the standardization was the live-timed
      4pibeta(LS)-gamma(NuaI(Tl)) anticoincidence counting. The live-timed
      anticoincidence system is operated since 2006 in LNMRI and is composed of two
      MTR2 modules donated by Laboratoire National Henri Becquerel (LNE-LNHB)/France.
      The data acquisition system uses a homemade LabView program and an Excel file for
      calculus. These systems have been used for primary standardization at LNMRI for
      many radionuclides and recently took part in the (124)Sb and (177)Lu
      International Key Comparisons with good performance.

PMID- 22417697
TI  - Determination of micelle size in some commercial liquid scintillation cocktails.
AB  - Dynamic light scattering measurements were performed on commercially available
      liquid scintillation (LS) cocktails over a range of aqueous and acid contents. In
      all cases, measured hydrodynamic diameters were substantially smaller than the
      current de facto canonical value of 8 nm. Cocktail compositions that yield stable
      micelles are described and the observed diameters are reported. Calculations of
      the magnitude of the "micelle effect" on LS counting efficiencies and the error
      introduced by adopting an incorrect value for the micelle size are also
      discussed.

PMID- 22417698
TI  - Measurement of anisotropic angular distributions of photon energy spectra for I
      125 brachytherapy sources.
AB  - The angular distribution of photon energy spectra emitted from an I-125
      brachytherapy source was measured using a specially designed jig in the range of
      +/-70 degrees  in the plane of the long axis of the source. It is important to
      investigate the angular dependence of photon emissions from these sources for the
      calibration of the air kerma rate. The results show that the influence of the
      distributions between 0 degrees  and +/-8 degrees  is small enough to allow a
      calibration using current primary instruments which have a large entrance window.

PMID- 22417699
TI  - Standardization of 64Cu and 68Ga by the 4pi(PC)beta-gamma coincidence method and
      calibration of the ionization chamber.
AB  - The paper treats the application of the 4pi(PC)beta-gamma coincidence method for
      the standardization of the radionuclides (64)Cu and (68)Ga. The general
      coincidence equations are written. Two types of extrapolation were described and
      used in measurement: the positron-annihilation coincidence, and the counting of
      all emitted radiations; both methods are compared with respect to results,
      advantages and drawbacks. The impurities' content correction was applied. The
      standardized solutions were used to calibrate the ionization chamber CENTRONIC
      IG12/20A and to determine the gamma-rays emission intensities.

PMID- 22417700
TI  - Evaluating practicability of an LSC method for routine monitoring gross alpha and
      beta activities in water samples in Taiwan.
AB  - A procedure using liquid scintillation counting for the monitoring of gross alpha
      and beta activities in environmental water was implemented to improve the
      conventional procedure using GFPC adopted in Taiwan. The new procedure was
      acquired through calibration and validation, and then was applied to the
      monitoring of surface water in Taiwan. This procedure can improve 2-4 times of
      detection efficiencies and takes only 70-80% of analysis time with reliable
      accuracy. With these features, the newly developed procedure is favorable during
      emergency situations.

PMID- 22417701
TI  - Cis-vaccenic acid and the Framingham risk score predict chronic kidney disease:
      the multi-ethnic study of atherosclerosis (MESA).
AB  - INTRODUCTION: Data on the associations of fatty acids with chronic kidney disease
      (CKD) are sparse. MATERIALS AND METHODS: We performed a cross-sectional study of
      2792 men and women from the MESA cohort of African-American, Caucasian, Chinese
      and Hispanic adults without known cardiovascular disease. Plasma phospholipid
      fatty acid proportions were associated with estimated glomerular filtration rate
      (eGFR) and the albumin/creatinine ratio. RESULTS: Cis-vaccenic acid (18:1n-7),
      adjusted for other fatty acids using multivariate logistic regression (CI: 1.0
      1.4), and step-wise logistic regression (CI: 1.02-1.42), was positively
      associated with reduced eGFR. The Framingham Risk Score, when adjusting for fatty
      acid proportions and demographic factors, was positively associated with CKD as
      measured by the eGFR and the albumin/creatinine ratio. DISCUSSION AND
      CONCLUSIONS: Plasma phospholipid proportions of the 18 carbon monounsaturated cis
      vaccenic acid {18:1n-7}) and the Framingham Risk Score are associated with kidney
      function. The potential role of 18:1n-7 in the development of CKD warrants
      further investigation.

PMID- 22417702
TI  - Urinary concentrations of benzophenone-type UV filters in U.S. women and their
      association with endometriosis.
AB  - Benzophenone (BP)-type UV filters are widely used in a variety of personal care
      products for the protection of skin and hair from UV irradiation. Despite the
      estrogenic potencies of BP derivatives, few studies have examined the occurrence
      of these compounds in human matrices. Furthermore, associations among exposure to
      these compounds and estrogen-dependent diseases (such as endometriosis) have not
      been examined previously. In this study, we determined the concentrations of five
      BP derivatives, 2-hydroxy-4-methoxybenzophenone (2OH-4MeO-BP), 2,4
      dihydroxybenzophenone (2,4OH-BP), 2,2'-dihydroxy-4-methoxybenzophenone (2,2'OH
      4MeO-BP), 2,2',4,4'-tetrahydroxybenzophenone (2,2',4,4'OH-BP), and 4
      hydroxybenzophenone (4OH-BP), in urine collected from 625 women in Utah and
      California, using liquid chromatography (LC)-tandem mass spectrometry (MS/MS).
      The association of urinary concentrations of BP derivatives with an increase in
      the odds of a diagnosis of endometriosis was examined in 600 women who underwent
      laparoscopy/laparotomy (n = 473: operative cohort) or pelvic magnetic resonance
      imaging (n = 127: population cohort), during 2007-2009. 2OH-4MeO-BP, 2,4OH-BP,
      and 4OH-BP respectively were detected in 99.0%, 93.3%, and 83.8% of the urine
      samples analyzed, whereas the detection rates for 2,2',4,4'OH-BP and 2,2'OH-4MeO
      BP were below 6.0%. Significant regional differences (higher concentrations in
      California) and monthly variations (higher concentrations in July and August)
      were found for urinary concentrations of 2OH-4MeO-BP and 2,4OH-BP. In addition,
      urinary concentrations of 2OH-4MeO-BP and 2,4OH-BP tended to be higher in more
      affluent, older, and leaner women. Adjusted odds ratios (ORs) and 95% confidence
      intervals (CIs) were estimated for the urinary concentrations of BP derivatives
      and the odds of an endometriosis diagnosis; ORs increased across quartiles of 2OH
      4MeO-BP and 2,4OH-BP concentrations, but a significant trend was observed only
      between 2,4OH-BP and the odds of an endometriosis diagnosis in the operative
      cohort (OR = 1.19; 95% CI = 1.01, 1.41). When women in the highest quartile of
      2,4OH-BP concentrations were compared with women in the first three quartiles,
      the OR increased considerably (OR = 1.65; 95% CI = 1.07, 2.53). Given that 2,4OH
      BP possesses an estrogenic activity higher than that of 2OH-4MeO-BP, our results
      invite the speculation that exposure to elevated 2,4OH-BP levels may be
      associated with endometriosis.

PMID- 22417703
TI  - Bronchoscopic lung biopsy using noninvasive ventilatory support: case series and
      review of literature of NIV-assisted bronchoscopy.
AB  - BACKGROUND: Fiberoptic bronchoscopy and lung biopsy are important diagnostic
      tools in patients with diffuse pulmonary infiltrates. However, these patients
      often have hypoxemic respiratory failure that makes this procedure hazardous.
      Noninvasive ventilation (NIV) has been shown to improve  oxygenation in hypoxemic
      patients. OBJECTIVE: To report the efficacy and safety of an innovative technique
      of NIV-assisted bronchoscopic lung biopsy in a small case-series of hypoxemic
      subjects with diffuse parenchymal infiltrates; also to systematically review the
      literature on NIV-assisted  bronchoscopy. METHODS: Subjects with bilateral
      diffuse parenchymal infiltrates and P(aO(2))/F(IO(2)) < 200 mm Hg underwent
      bronchoscopic lung biopsy under NIV support. NIV was initiated 10 min before the
      procedure and continued for 30 min after the procedure.  The primary outcomes
      were performance of successful procedure and episodes of decline in S(pO(2)) <
      90%. Secondary end points were the change in the respiratory and hemodynamic
      parameters during the procedure and occurrence of complications such as
      pneumothorax, hemorrhage,  and endotracheal intubation. RESULTS: Six subjects,
      with a mean +/- SD age of 44.5 +/- 11.6 years, were included in the study. The
      median (interquartile range [IQR]) P(aO(2))/F(IO(2)) prior to lung biopsy was
      164.5 mm Hg (146.3-176.3 mm  Hg), and the median (IQR) inspiratory and expiratory
      positive airway pressures were 14 cm H(2)O (12-15 cm H(2)O) and 5 cm H(2)O.
      Fiberoptic bronchoscopy was well tolerated and all subjects maintained S(pO(2)) >
      92% during the procedure.  One subject required endotracheal intubation due to
      hemoptysis. A definite diagnosis was obtained in 5 of the 6 subjects. A repeat
      procedure was performed in one subject, which again yielded no diagnosis. No
      other periprocedural complications were encountered. CONCLUSIONS: NIV-assisted
      bronchoscopic  lung biopsy is a novel method for obtaining diagnosis in hypoxemic
      patients with diffuse lung infiltrates. However, this approach should be reserved
      for centers with extensive experience in NIV. More studies are required to define
      the utility of this approach.

PMID- 22417705
TI  - Prevalence of serological markers and risk factors for bloodborne pathogens in
      Salvador, Bahia state, Brazil.
AB  - This study aimed to determine the prevalence of serological markers for HIV-1/2,
      HBV, HCV, Treponema cruzi and T. pallidum infections. The association of these
      infections with risk factors in a population from Salvador, Bahia, Brazil was
      also analysed. Of the 780 enrolled individuals, 545 (70%) were female and 235
      (30%) were male. Seroprevalence of 0.8% (6/702), 1.3% (9/678), 1.5% (10/684),
      3.5% (23/663) and 11.5% (77/668) for HIV-1/2, HBV, HCV, T. cruzi and T. pallidum
      infections, respectively, was observed. The seroprevalence of T. pallidum was
      higher in males 20% (43/210) than in females 7% (34/458) (P < 0.01). An
      association between age and seroprevalence for T. cruzi (P = 0.02) and T.
      pallidum (P < 0.01) was observed. HBsAg was associated with having tattoos (3/37
      vs. 6/623, P = 0.01) and not having a steady sexual partner (5/141 vs. 4/473, P =
      0.04), while anti-HIV-1/2 was associated with having tattoos (2/39 vs. 4/647, P =
      0.04); however, larger studies are needed to categorically state the relationship
      of these risk factors with infectious agents. The prevalence of serological
      markers for HIV-1/2, HBV, HCV and T. cruzi was consistent with other studies.

PMID- 22417704
TI  - Postoperative adjuvant transcatheter arterial chemoembolisation improves survival
      of intrahepatic cholangiocarcinoma patients with poor prognostic factors: results
      of a large monocentric series.
AB  - BACKGROUND: The prognosis of patients with intrahepatic cholangiocarcinoma (ICC)
      is currently unsatisfactory. The aims of this study were to identify prognostic
      factors after curative ICC resection, and to evaluate the effects of
      postoperative transcatheter arterial chemoembolisation (TACE). METHODS: A
      retrospective analysis was conducted of 114 ICC patients who underwent curative
      resection from January 2005 to December 2006. Relationships between survival and
      clinicopathological factors were evaluated using univariate and multivariate
      analyses. The benefits of adjuvant TACE were investigated separately. RESULTS:
      The cumulative 1-, 3-, and 5-year survival rates were 63%, 26%, and 15%,
      respectively. Multivariate analysis revealed that tumour size >= 5 cm (hazard
      ratio [HR] 1.875, 95% CI 1.139-3.088, P=0.013) and advanced TNM stage (stage III
      or IV) (HR 1.681, 95% CI 1.035-2.732, P=0.036) were independently associated with
      poor prognosis. Fifty-seven patients underwent adjuvant TACE. In patients with
      poor prognostic factors, TACE improved the survival rate (P<0.001). However, in
      patients without poor prognostic factors, TACE did not significantly change the
      survival rate (P=0.724). CONCLUSIONS: Postoperative adjuvant TACE can prolong
      survival in ICC patients with tumour size >= 5 cm or advanced TNM stage.

PMID- 22417706
TI  - The adaptor protein FHL2 enhances the cellular innate immune response to
      influenza A virus infection.
AB  - The innate immune response of influenza A virus-infected cells is predominantly
      mediated by type I interferon-induced proteins. Expression of the interferon beta
      (IFNbeta) itself is initiated by accumulating viral RNA and is transmitted by
      different signalling cascades that feed into activation of the three
      transcriptional elements located in the IFNbeta promoter, AP-1, IRF-3 and NF
      kappaB. FHL2 (four-and-a-half LIM domain protein 2) is an adaptor molecule that
      shuttles between membrane and nucleus regulating signalling cascades and gene
      transcription. Here we describe FHL2 as a novel regulator of influenza A virus
      propagation. Using mouse FHL2 wild-type, knockout and rescued cells and human
      epithelial cells with different expression levels of FHL2 we showed that FHL2
      decreases influenza A virus propagation by regulating the intrinsic cellular
      antiviral immune response. On virus infection FHL2 translocates into the nucleus,
      potentiating the IRF-3-dependent transcription of the IFNbeta gene.

PMID- 22417707
TI  - Can mesenchymal stem cells reduce vulnerability of dopaminergic neurons in the
      substantia nigra to oxidative insult in individuals at risk to Parkinson's
      disease?
AB  - PD (Parkinson's disease) is characterized by the selective loss of DA
      (dopaminergic) neurons in the substantia nigra of the midbrain region, but not in
      the ventral tegmental area and other catecholaminergic cell group areas. The
      aetiology of PD is attributed both to environmental and genetic causes, and
      certain population of individuals may be classified as at risk of developing PD
      later in life. However, there are as yet no therapy regimens that can help to
      delay or prevent the onset of the disease to realize long-term benefits from this
      early diagnosis. In PD, a vicious cycle gets initiated in the substantia nigra,
      because of which susceptible neurons continue to degenerate whereas damaged
      neurons do not get enough support for regeneration. This happens primarily
      because of the local environment of oxidative damage brought about by the dual
      presence of dopamine and high levels of iron, decline in cellular detoxification
      systems and low density of glial cells surrounding the DA neurons in the
      mesencephalic region. To enhance the defence mechanism of the substantia nigra in
      this situation, it is necessary to combat the oxidative insult while providing
      trophic factors for the survival and regeneration of the damaged neurons. In
      light of in vitro and in vivo studies, MSCs (mesenchymal stem cells) as
      candidates for cell-based therapies in PD have greater scope than as mere
      replacement of cell type, since they can be used as a cellular system for the
      detoxification of ROS (reactive oxygen species) as well as a supplier of
      neurotrophic factors to modulate the local environment. Building on progress in
      unravelling the multipronged effect of MSCs, we therefore hypothesize that MSCs
      could be used as a prophylactic strategy to delay or prevent the onset of PD in
      at-risk individuals, and to slow down the progression of the disease.

PMID- 22417708
TI  - The influence of antidiabetic medications on the development and progression of
      prostate cancer.
AB  - BACKGROUND: The development of prostate tumors has been linked to co-morbid
      diabetes mellitus (DM) in several studies, potentially through the stimulation of
      insulin-like growth factor receptor (IGFR). This study evaluates the effect of
      anti-diabetic medication use on the development of high grade tumors and time to
      tumor progression compared to non-diabetics. METHODS: This retrospective, nested
      case control study identified patients with prostate cancer (PCa) from the
      Kentucky Medicaid Database. Cases were diagnosed with PCa and DM and using at
      least one of the following antidiabetic medications; sulfonylureas, insulin,
      metformin or TZDs. Cases were further stratified on their insulin exposure
      resulting from therapy. Controls were those with PCa without DM or any anti
      diabetic medications. RESULTS: The use of metformin or TZDs trended toward
      decreased odds of high-grade tumors and decreased risk of progression, while
      sulfonylureas and high-dose insulin tended toward an increased odds of high-grade
      tumors and increase the risk of progression compared to non-diabetics.
      CONCLUSIONS: Future studies should be conducted to further evaluate the effects
      of anti-diabetic medications on tumor grade and time to prostate cancer
      progression.

PMID- 22417709
TI  - TLR2 ligation induces the production of IL-23/IL-17 via IL-6, STAT3 and NF-kB
      pathway in patients with primary Sjogren's syndrome.
AB  - INTRODUCTION: The study was undertaken to investigate the interrelation of toll
      like receptor (TLR) and interleukin (IL)-17 in the salivary glands of patients
      with primary Sjogren's syndrome (pSS) and to determine the role of TLR and IL-17
      in the pathophysiology of pSS. METHODS: The expressions of various TLRs, IL-17
      and the cytokines involved in Th17 cell differentiation including IL-6, IL-23,
      tumor necrosis factor-alpha (TNF-alpha) and IL-1beta were examined by
      immunohistochemistry in salivary glands of pSS patients. The IL-17 producing CD4+
      T cells (Th17 cells) were examined by flow cytometry and confocal staining in
      peripheral mononuclear blood cells (PMBCs) and salivary glands of pSS patients.
      After PBMCs were treated with TLR specific ligands, the induction of IL-17 and IL
      23 was determined using real-time PCR and ELISA. The signaling pathway that
      mediates the TLR2 stimulated production of IL-17 and IL-23 was investigated by
      using treatment with specific signaling inhibitors. RESULTS: We showed that TLR2,
      TLR4, TLR6, IL-17 and the cytokines associated with Th17 cells were highly
      expressed in salivary glands of pSS patients but not in controls. The expressions
      of TLR2, TLR4 and TLR6 were observed in the infiltrating mononuclear cells and
      ductal epithelial cells, whereas IL-17 was mainly observed in infiltrating CD4+ T
      cells. The number of IL-17 producing CD4+ T cells was significantly higher in pSS
      patients both in PBMCs and minor salivary glands. The stimulation of TLR2, TLR4
      and TLR6 additively induced the production of IL-17 and IL-23 from the PBMCs of
      pSS patients especially in the presence of TLR2 stimulation. IL-6, signal
      transducer and activator of transcription 3 (STAT3) and nuclear factor-kappaB (NF
      kB) pathways were implicated in the TLR2 stimulated IL-17 and IL-23. CONCLUSIONS:
      Our data demonstrate that TLR2 ligation induces the production of IL-23/IL-17 via
      IL-6, STAT3 and NF-kB pathway in pSS. Therefore, therapeutic strategies that
      target TLR/IL-17 pathway might be strong candidates for treatment modalities of
      pSS.

PMID- 22417710
TI  - Metabolism of SO2 binding compounds by Oenococcus oeni during and after
      malolactic fermentation in white wine.
AB  - Sulfur dioxide SO2 is the key additive for the preservation of wines. Carbonyl
      and keto compounds in wine can bind to SO2 and decrease its efficacy, resulting
      in higher total SO2 requirements. Increased consumer demand for low sulfite and
      organic wines pose production challenges if SO2 binders have not been properly
      managed during vinification. Malolactic fermentation (MLF) has been known to
      reduce bound SO2 levels but detailed time course studies are not available. In
      this work, the kinetics of major SO2 binding compounds and malic acid were
      followed during MLF in wine with 12 commercially available strains of Oenococcus
      oeni. Pyruvic acid, acetaldehyde and alpha-ketoglutaric acid were degraded to
      various degrees by O. oeni, but galacturonic acid was not. At the time of malic
      acid depletion, percent degradation of pyruvate, alpha-ketoglutaric acid and
      acetaldehyde was 49%, 14% and 30%, respectively. During MLF, the decrease in
      average bound SO2 levels, as calculated from carbonyl metabolism, was 22%. The
      largest reduction in wine carbonyl content occurred in the week after completion
      of MLF and was 53% (107 mg/L to 34 mg/L) calculated as bound SO2. Prolonged
      activity of bacteria in the wines (up to 3 weeks post malic acid depletion)
      resulted only in reduced additional reductions in bound SO2 levels. The results
      suggest that microbiological wine stabilization one week after malic acid
      depletion is an effective strategy for maximum removal of SO2 binders while
      reducing the risk of possible post-ML spoilage by O. oeni leading to the
      production acetic acid and biogenic amines.

PMID- 22417711
TI  - Focal presence of molluscum contagiosum in basal cell carcinoma.

PMID- 22417712
TI  - ARDS secondary to descending necrotizing mediastinitis treated by long-term
      extracorporeal respiratory support.

PMID- 22417713
TI  - Effects of CYP4F2 polymorphism on response to warfarin during induction phase: a
      prospective, open-label, observational cohort study.
AB  - BACKGROUND: The cytochrome P450 (CYP) 4F2 isozyme has been reported to metabolize
      vitamin K(1) in vitro, and the V433M polymorphism in the CYP4F2 gene has been
      associated with reduced vitamin K(1) metabolism and the need for a higher
      maintenance dosage in patients receiving warfarin. OBJECTIVE: The purpose of the
      present study was to evaluate the effects of V433M polymorphism on warfarin
      response during the induction phase. METHODS: Warfarin-naive white patients in
      whom warfarin was scheduled to be initiated with a target INR of 2 to 3 were
      enrolled into the study. On enrollment, a single blood sample for the genotyping
      of CYP4F2, CYP2C9, and VKORC1 was drawn. The international normalized ratio (INR)
      was followed daily during induction and twice weekly until stable anticoagulation
      was reached. The relationships between several markers of warfarin response
      during induction and CYP4F2 polymorphism were determined. RESULTS: The cohort
      consisted of 241 patients (115 men; mean [SD] age, 55.2 [19.4] years; weight,
      79.5 [18.3] kg). Most of the patients were carriers of the CYP4F2 CC genotype
      (112 patients) or the CT genotype (104 patients). In carriers of the TT genotype
      (25 patients), INR >3 was >4-fold lower compared with that in carriers of the CC
      or CT genotype, suggesting that patients with the TT genotype were less sensitive
      to warfarin during induction. Also in TT carriers, the extent of excessive
      anticoagulation was >10-fold lower than in the other carriers. Both of these
      findings had a nominal P value of <0.05. After adjustment for false discovery
      rate, none of the findings remained significant at a threshold q value of <0.05.
      Among CC carriers, the concurrent use of a statin was associated with a 1-mg/d
      reduction in warfarin maintenance dosage. No similar effect was noted in the CT
      or TT carriers, suggesting a possible genetic influence on warfarin-statin
      interaction. CONCLUSIONS: These preliminary findings suggest that among white
      patients treated with warfarin, CYP4F2 polymorphism had a measurable effect on
      warfarin responsiveness during induction; however, the observed differences
      failed to reach the level of statistical significance. The possibility that the
      effect of statins on warfarin anticoagulation varies among carriers of different
      CYP4F2 genotypes could not be excluded and should be evaluated further in a
      larger patient sample.

PMID- 22417714
TI  - Medicare part D research and policy highlights, 2012: impact and insights.
AB  - BACKGROUND: In the 6 years since the implementation of Medicare Part D in the
      United States, the program has been reported to improve quality, offer better
      beneficiary protections, and lower drug costs. OBJECTIVE: The purpose of this
      article was to highlight the latest key peer-reviewed research findings on
      Medicare Part D and major public policy initiatives for Part D for 2012. METHODS:
      PubMed was searched for studies on Medicare Part D published in 2011 in
      biomedical/scientific, peer-reviewed, English-language journals. For the policy
      update, sources included the Federal Register, the Medicare Prescription Drug
      Benefit Manual, the 2012 Final Call Letter, and guidance from the Centers for
      Medicare and Medicaid Services. RESULTS: Medicare Part D has been associated with
      increased medication utilization, reduced out-of-pocket expenditures, and an
      overall decrease in cost-related non-adherence and nonpersistence. Its impact on
      reduction in non-drug utilization of health services has been more apparent after
      the transition year in 2006 and among subsets of Medicare beneficiaries. Recent
      policy changes promise to make Part D more user-friendly, simplify choice, and
      offer greater protection to beneficiaries. The coverage gap will phase out by
      2020. Both the quality rating system for prescription drug plans and medication
      therapy management programs were enhanced. CONCLUSIONS: Although Part D was
      designed to improve drug benefits, improvements may be needed in plan selection
      and simplification, quality assessment (especially with regard to long-term
      impact and health outcomes), evidence-based improvements in medication therapy
      management, and disparities among priority subpopulations. Medicare Parts A, B,
      and D could be coordinated to offset costs by increasing medication expenses and
      decreasing expenses for nonprescription medical services, thereby improving the
      overall cost-effectiveness of the Medicare program.

PMID- 22417715
TI  - Assessment of the potential role of active vitamin D treatment in telomere
      length: a case-control study in hemodialysis patients.
AB  - BACKGROUND: Telomeres are special chromatin sequences located at the end of
      eukaryotic chromosomes, protecting these regions from recombination and
      degradation. Previous studies have reported a decrease in telomere length on
      white blood cells from hemodialysis (HD) patients, which suggests premature
      senescence. Active vitamin D treatment has been reported to have an effect on
      telomere length and beneficial effects on HD patients, but the mechanisms are
      unknown. OBJECTIVE: Our aim was to assess the potential protective role of active
      vitamin D treatment on telomere length in peripheral mononuclear cells (PBMC)
      from HD patients. METHODS: A retrospective case-control study of 62 stable HD
      patients and 60 healthy sex-matched controls was undertaken. Telomere length was
      measured in PBMC by Southern blot. After telomere length measurement, 5 control
      samples that did not reach quality-control standards were excluded. Standard
      epidemiological and biochemical parameters were recorded. Blood biochemistries
      were performed at the Biochemistry Department of the University Hospital Arnau de
      Vilanova in Lleida, Spain, using standard routine techniques. Differences in
      telomere length were analyzed using Student's t test. Multiple regression
      analysis examined the independent contribution of the factors that significantly
      affected telomere length in the bivariate analysis. RESULTS: HD patients
      presented shorter telomere length in PBMC, independent of age and sex (mean [SD]
      8.8 [1.5] kbp vs 10.5 [2.9] kbp; P = 0.0001). Multivariate regression analysis of
      the HD subgroup suggested that patients under active vitamin D treatment have
      greater telomere length in PBMC than untreated patients (9.5 [0.2] kbp vs 8.4
      [0.2] kbp; P = 0.003). CONCLUSIONS: HD patients were observed to have decreased
      PBMC telomere length compared with healthy controls. HD patients treated with
      active vitamin D compounds had greater PBMC telomere length than untreated
      patients. Prospective studies are required to assess the potential role of active
      vitamin D treatment in PBMC telomere length.

PMID- 22417716
TI  - New oral anticoagulants for atrial fibrillation: a review of clinical trials.
AB  - BACKGROUND: Warfarin had been the only oral anticoagulant for stroke prevention
      in patients with atrial fibrillation (AF) for decades. Direct thrombin inhibitors
      and factor Xa inhibitors are new anticoagulants recently approved for prevention
      of stroke or systemic embolism in patients with AF. OBJECTIVE: The aim of this
      article was to provide a systematic review of recently published clinical data on
      the direct thrombin inhibitors and factor Xa inhibitors in the management of AF.
      METHODS: A search of the ClinicalTrials.gov registry was conducted using the
      subject terms dabigatran, rivaroxaban, and apixaban. Each search was limited to
      clinical trials that included patients with AF. Completed studies with warfarin
      as the main comparator were identified. From the yielded results, the national
      clinical trial identifier was inputted in PubMed (1966-November 2011) for a
      search of published literature. RESULTS: Three Phase III clinical trials reported
      the efficacy of each agent in patients who have AF and risk factors for stroke or
      embolic complications. The Randomized Evaluation of Long-Term Anticoagulation
      Therapy (RE-LY) study reported dabigatran 150 mg was associated with a lower rate
      of stroke and systemic embolism, whereas dabigatran 110 mg was associated with a
      similar rate for such events when compared with warfarin (relative risk = 0.66;
      95% confidence interval [CI], 0.53-0.82; P < 0.001; and relative risk = 0.91; 95%
      CI, 0.74-1.11; P = 0.34, respectively). From the intention-to-treat analysis of
      the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin
      K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation
      (ROCKET AF) study, rivaroxaban was reported to be noninferior to warfarin in
      reducing stroke or systemic embolism (2.1% vs 2.4% per year; hazard ratio = 0.88;
      95% CI, 0.75-1.03; P < 0.001). The Apixaban for Reduction in Stroke and Other
      Thrombotic Events in Atrial Fibrillation (ARISTOTLE) trial reported that apixaban
      reduced stroke or systemic embolic events by 21% when compared with warfarin
      (1.27% vs 1.60% per year, respectively; hazard ratio = 0.79; 95% CI, 0.66-0.95; P
      < 0.001). All 3 agents were associated with similar bleeding when compared with
      warfarin. CONCLUSIONS: Published data suggest that all 3 agents are at least as
      efficacious as dose-adjusted warfarin, with similar major bleeding profiles. For
      patients who are unwilling to adhere to regular coagulation monitoring or whose
      therapeutic effect using warfarin is not optimal despite adequate monitoring and
      management, the inhibitors of direct thrombin or factor Xa may provide
      alternative choices in anticoagulation.

PMID- 22417718
TI  - Influence of the drill material and method of cooling on the development of
      intrabony temperature during preparation of the site of an implant.
AB  - Our aim was to evaluate the intrabony friction heat produced by implant drills,
      using different drill materials and methods of cooling. Four pilot drills and 4
      form drills were used. The following combinations of drill material and cooling
      supply were tested: steel and external cooling; steel and internal cooling; steel
      coated with zirconium nitride and external cooling; and zirconium oxide and
      external cooling. The handpiece that supported the drill was fixed in a lifting
      device. Specimens of bovine ribs were fixed below the handpiece, and the drill
      speed was set to 1200 rpm. The vertical force was adjusted to 1 kg for pilot
      drills and 0.5 kg for implant drills. Intrabony temperature during drilling was
      measured at depths of 4, 8, and 12 mm parallel to the drill, and the depth was
      limited to 13 mm. There were no significant differences in heat generation
      between the drill materials (p>.05), but the differences between groups with
      internal or external cooling supplies were significant (p<=.05). The method of
      cooling affected the development of the intrabony temperature during preparation
      of the site of the implant, but the drill material seemed to play no particular
      role.

PMID- 22417717
TI  - Cost-effectiveness of tapentadol in severe chronic pain in Spain: a cost analysis
      of data from RCTs.
AB  - BACKGROUND: Chronic pain is known to be a significant and common health problem.
      Tapentadol, a recently developed centrally active, oral analgesic agent is used
      to treat adults with severe chronic pain that can be adequately managed only with
      opioid analgesics. Tapentadol has been reported to provide an improved adverse
      events (AE) profile compared with other potent opioid analgesics at similar
      levels of analgesia. OBJECTIVES: The aim of this study was to compare the cost
      effectiveness of tapentadol to that of opioids commonly used as first-line
      treatment of severe, chronic, nonmalignant pain from the perspective of the
      health care payer in Spain. METHODS: A Markov state-transition model was
      developed to compare the cost-effectiveness of first-line treatment with
      tapentadol to that of oxycodone, morphine, and transdermal fentanyl (TDF) over a
      1-year time horizon. Four health states were defined: (1) treatment
      discontinuation due to a severe AE; (2) treatment discontinuation due to a lack
      of efficacy; (3) occurrence of an AE that required medical treatment; and (4) no
      discontinuation and no AE. If a patient discontinued a treatment, he or she was
      switched to an alternative, second-line opioid. Data regarding efficacy,
      tolerability, and utility values (EQ-5D) were derived from randomized clinical
      trials. Clinical experts estimated the rates of switching to other opioids and
      the health care resource utilization associated with the treatment of severe
      chronic pain. Unit costs were derived from public price lists/tariff works and
      were calculated from the perspective of the National Spanish Health System. The
      robustness of the model results was tested in extensive sensitivity analyses in
      which event probabilities, costs, utilities, and treatment-switching rates were
      altered. RESULTS: Data from 3 studies (1981 patients) were included in the model.
      Overall, the model predicted that initiating first-line treatment with tapentadol
      in patients with severe, chronic, nonmalignant pain was associated with lower
      costs and greater efficacy versus first-line treatment with oxycodone. Compared
      with morphine and TDF, tapentadol yielded incremental cost-effectiveness ratios
      of ?2656 and ?2069 per quality-adjusted life-year gained, respectively. On
      extensive 1-way and scenario analyses, findings on the cost-effectiveness of
      tapentadol were consistent. The probability that tapentadol would be cost
      effective compared with each comparator at the willingness-to-pay threshold of
      ?20,000 to ?30,000/QALY gained exceeded 90%. CONCLUSIONS: Based on the findings
      from the present model, tapentadol is likely to be a cost-effective first-line
      treatment in patients with severe, chronic, nonmalignant pain in Spain according
      to the commonly accepted willingness-to-pay thresholds. Compared with morphine
      and TDF, the incremental cost-effectiveness ratios were low; compared with
      oxycodone, tapentadol dominated, showing better quality-of-life outcomes at lower
      costs.

PMID- 22417719
TI  - The rCBF brain mapping in adolescent ADHD comorbid developmental coordination
      disorder and its changes after MPH challenging.
AB  - BACKGROUND: Comorbid developmental coordination disorder (DCD) in the patients
      with attention-deficit hyperactivity disorder (ADHD) often complicated the
      treatment strategy. Methylphenidate (MPH) improves the coordination problem in
      patients with ADHD. AIM: The study intended to investigate the pathophysiology
      and the mechanisms of MPH in comorbid DCD of the adolescents with ADHD. METHODS:
      Brain images using technetium-99m ethyl cysteinate dimmer ((99m)Tc-ECD) single
      photon emission computed tomography (SPECT) were done in 10 drug-naive
      adolescents with ADHD without DCD and 5 adolescents with ADHD comorbid DCD. The
      baseline rCBF and changes of rCBF after 10 mg MPH challenge between two groups
      were compared using statistical parametric mapping (SPM99) analysis. RESULTS:
      Lower rCBF of bilateral frontal lobe, inferior parental lobe, and increased rCBF
      of right posterior cingulate gyrus, anterior lobe of cerebellum were found in
      ADHD comorbid DCD group compared to ADHD without DCD group. Decreased rCBF in the
      right occipital, inferior temporal lobe was found in ADHD comorbid DCD group
      after MPH while ADHD alone group revealed increased rCBF in bilateral occipital
      lobe. CONCLUSIONS: The results help us understand the pathophysiology of DCD in
      ADHD adolescents. The different rCBF response to MPH provides a clue for future
      intervention of DCD in ADHD adolescents.

PMID- 22417720
TI  - Rest left ventricular function and contractile reserve by dobutamine stress
      echocardiography in peripartum cardiomyopathy.
AB  - AIMS: To assess whether contractile reserve during dobutamine stress
      echocardiography (DSE) can predict left ventricular functional recovery in
      patients with peripartum cardiomyopathy and to assess myocardial fibrosis by
      magnetic resonance imaging (MRI) in these patients. METHODS: Nine patients with
      peripartum cardiomyopathy were enrolled. All patients underwent DSE and were
      followed for six months, when a rest Doppler echocardiogram was repeated. MRI was
      also performed at the beginning of follow-up to identify myocardial fibrosis.
      RESULTS: Mean age was 29+/-7.9 years and mean left ventricular ejection fraction
      at baseline was 39.4+/-8.6% (range 24-49%). Eight of the nine patients showed
      left ventricular functional recovery with mean ejection fraction at follow-up of
      57.1+/-13.8%. The ejection fraction response to DSE did not predict recovery at
      follow-up. On the other hand, left ventricular ejection fraction at baseline
      correlated with ejection fraction at follow-up. Mild fibrosis was detected in
      only one patient. CONCLUSION: Left ventricular ejection fraction at baseline was
      a predictor of left ventricular functional recovery in patients with peripartum
      cardiomyopathy. Dobutamine stress echocardiography at presentation of the disease
      did not predict recovery at follow-up. Myocardial fibrosis appeared to be
      uncommon in this cardiomyopathy.

PMID- 22417721
TI  - About Brugada syndrome and its prevalence.

PMID- 22417722
TI  - The anatomical characteristics of three different endocardial lines in the left
      atrium: evaluation by computed tomography prior to mitral isthmus block attempt.
AB  - AIMS: Additional linear ablation lesions are created to improve the outcomes of
      pulmonary vein (PV) isolation during atrial fibrillation (AF) ablation. We aimed
      to evaluate the safety and feasibility of additional ablation sites in terms of
      anatomical characteristics. METHODS AND RESULTS: Multi-detector computed
      tomography (MDCT) data from 140 consecutive patients (40 with AF, 84 males, 59 +/
      11 years old) and additional 10 heart specimens were analysed for their
      anatomical characteristics at three types of mitral isthmus lines: anteromedial
      (AM), anterolateral (AL), and posterolateral (PL) lines (from right superior,
      left superior, and left inferior PV to 10, 12, and 4 o'clock position of the
      mitral annulus, respectively). The data demonstrated that the length was shortest
      at the PL lines (MDCT, 36.4 +/- 8.6 mm; specimens, 31 +/- 6 mm) and the maximal
      myocardial thickness was greatest at the AL lines (MDCT, 3.2 +/- 1.0 mm;
      specimens, 5.0 +/- 0.9 mm). Ridge, cord-like structure, or diverticulum was found
      most frequently at the AM lines (MDCT, 20%; specimens, 20%). Sinus nodal artery
      (SNA) was found near the AM (MDCT, 100%; specimens, 90%) and AL lines (MDCT,
      46.3%; specimens, 30%), while left coronary artery (LCA) and cardiac vein were
      closest to the PL lines. The trend of these findings was not significantly
      altered with the presence of AF. CONCLUSIONS: The PL lines were shortest among
      the three mitral isthmus lines, but closest to LCA. Myocardium was thickest at
      the AL line, and SNAs were frequently found on the anterior lines. Multi-detector
      computed tomography provided detailed information, and further studies are
      required to clarify the clinical impact of these findings.

PMID- 22417723
TI  - Acute electrical isolation is a necessary but insufficient endpoint for achieving
      durable PV isolation: the importance of closing the visual gap.
AB  - AIMS: Temporary, ablation-mediated effects such as oedema may cause reversible
      pulmonary vein (PV) isolation. To investigate this, point-by-point
      circumferential ablation was performed to achieve acute electrical PV isolation
      with an incomplete circumferential ablation line. Then, the impact of this
      intentional 'visual gap' (ViG) on the conduction properties of the ablation
      lesion set was assessed with adenosine and pacing manoeuvres. METHODS AND
      RESULTS: Twenty-eight patients undergoing ablation for paroxysmal (n= 20) or
      persistent atrial fibrillation (n= 8) were included. Pulmonary vein (PV) ablation
      was performed around ipsilateral vein pairs. Once acute isolation was achieved,
      ablation was halted and the presence and size of the ViG were calculated. The ViG
      electrophysiological properties were tested with pace capture along the ViG at 10
      mA/2 ms, and assessment for dormant PV conduction with adenosine. Despite
      electrical isolation, a ViG was present in 75% (n= 42/56) of vein pairs (21 of 28
      left PVs and 21 of 28 right PVs). There was no difference in the ViG size between
      the left and right PVs (22.1 +/- 14.2 and 17.3 +/- 11.3 mm, P > 0.05). Dormant PV
      connections were revealed by adenosine in more than a quarter (n= 12/42) of
      acutely isolated PV pairs, of which the majority were dependent on conduction
      through the ViG. CONCLUSIONS: Electrical PV isolation can usually be achieved
      without complete circumferential ablation. However, more than a quarter of these
      'isolated' PVs exhibit dormant conduction-predominantly via the un-ablated 'ViGs'
      in the ablation lesion set. These findings support the hypothesis that reversible
      tissue injury contributes to PV isolation that may be acute but not necessarily
      durable.

PMID- 22417724
TI  - Calmidazolium selectively inhibits exocytotic glutamate release evoked by P2X7
      receptor activation.
AB  - We previously observed that activation of presynaptic P2X7 receptors located on
      rat cerebrocortical nerve terminals induced the release of glutamate through
      different modes: the channel conformation allowing Ca(2+) entry triggered
      exocytotic release, while the receptor itself functioned as a permeation pathway
      for the non-exocytotic glutamate release. Considering that exocytotic and non
      exocytotic glutamate release evoked by the activation of P2X7 receptors might
      play a role in the control of glutamatergic synapses, we investigated whether
      calmidazolium (which has been found to inhibit small cation currents through
      recombinant P2X7 receptors, but not organic molecule permeation) could
      distinguish between P2X7-related exocytotic and non-exocytotic modes of glutamate
      release. We found that calmidazolium inhibited the intrasynaptosomal Ca(2+)
      response to P2X7 receptor activation and the Ca(2+)-dependent exocytotic
      glutamate release from rat cerebrocortical nerve terminals, but was ineffective
      against the Ca(2+)-independent glutamate release. The P2X7 competitive antagonist
      A-438079 eliminated both exocytotic and non-exocytotic P2X7 receptor-evoked
      glutamate release. Selective inhibition of exocytotic glutamate release indicates
      that calmidazolium inhibits events dependent on the function of native rat P2X7
      receptors as Ca(2+) channels, and suggests that it can be used as a tool to
      dissociate P2X7-evoked exocytotic from non-exocytotic glutamate release.

PMID- 22417725
TI  - Chronic nicotine exposure selectively activates a carrier-mediated release of
      endogenous glutamate and aspartate from rat hippocampal synaptosomes.
AB  - The effect of chronic nicotine treatment on the release of endogenous glutamate
      (GLU), aspartate (ASP) and GABA evoked in vitro by KCl, 4-aminopyridine (4AP) and
      nicotinic agonists in synaptosomes of rat hippocampus was investigated. Rats were
      chronically administered with nicotine bitartrate or saline vehicle each for 14
      days using osmotic mini-pumps. Hippocampal synaptosomes were stimulated with KCl,
      4AP, nicotine or with choline (Ch) and 5-iodo-A-85380 dihydrochloride (5IA85380).
      The GLU and ASP overflow evoked by Ch, nicotine, KCl and 4AP were increased in
      treated animals while the nicotine-evoked GABA overflow was reduced and that
      evoked by Ch, KCl and 4AP was unaffected. The 5IA85380-evoked overflow of the
      three aminoacids (AAs) was always reduced. The increase of ASP and GLU overflow
      evoked by KCl, 4AP or Ch was blocked by dl-threo-beta-benzyloxyaspartic acid (dl
      TBOA), a carrier transporter inhibitor, and by inhibitors of the Na(+)/Ca(2+)
      exchangers 2-[[4-[(4-nitrophenyl)methoxy]phenyl]methyl]-4-thiazolidinecarboxylic
      acid ethyl ester (SN-6) and 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea
      mesylate (KB-R7943). In conclusion long-term nicotine treatment may selectively
      increase GLU and ASP overflow elicited by KCl, 4AP and Ch through the activation
      of a carrier-mediated release mechanism and completely abolished the stimulatory
      effects of alpha4beta2 nAChRs which modulate the release of all the three AA.

PMID- 22417726
TI  - AGEs-RAGE mediated up-regulation of connexin43 in activated human microglial CHME
      5 cells.
AB  - Microglial activation is a significant contributor to the pathogenesis of many
      neurodegenerative diseases. Microglia respond to a range of stimuli including
      pathogenic protein deposits such as advanced glycation endproducts (AGEs). AGEs
      are prominent inflammatory stimuli that accumulate in the ageing brain. AGEs can
      activate microglia, leading to the production of excessive amounts of
      inflammatory cytokines and coupling via gap junction proteins especially
      connexin43 (Cx43). The literature on the expression of microglial Cx43 during
      inflammation is controversial. Many cellular effects of AGEs are thought to be
      mediated by the receptor RAGE. There is however, no evidence suggesting Cx43 is a
      downstream effector of AGEs-RAGE interaction in microglia. In addition, most of
      the AGEs-related studies have been undertaken using rodent microglia; the
      information on human microglia is sparse. Microglia of human and rodent origin
      respond differently to certain stimuli. The aims of this study were to
      investigate the AGEs-RAGE-mediated activation of human microglia and establish if
      Cx43 is one of the downstream effectors of AGEs-RAGE interaction in these cells.
      Human microglial CHME-5 cells were treated with different doses of AGEs for a
      selected time-period and microglial activation studied using specific markers.
      The protein expression of RAGE, Cx43 and TNF-alpha-receptors (RI and RII) was
      analysed in response to AGEs in the absence/presence of various doses of anti
      RAGE Fabs. TNF-alpha levels in media were measured using ELISA. TNF-alpha-induced
      opening of gap junctional channels was assessed by dye uptake assays and the
      effect of neutralising TNFRII on Cx43 levels was also studied. CHME-5 cells
      showed an up-regulation of RAGE, TNF-alpha, TNFRs (especially TNFRII) and Cx43
      upon AGEs treatment and a significant dose-dependent drop in the levels of TNF
      alpha, TNFRII and Cx43 in the presence of anti-RAGE Fabs. TNF-alpha induced gap
      junctional/hemichannel opening whereas blocking TNFRII inhibited TNF-alpha
      induced increase in Cx43 levels. Results suggested that TNF-alpha, TNFRII and
      Cx43 are downstream effectors of the AGEs-RAGE interaction in human microglial
      CHME-5 cells.

PMID- 22417727
TI  - Age-dependent changes in the subcallosal zone neurogenesis of mice.
AB  - There are several known neurogenic areas including subventricular zone and
      subgranular layer in the dentate gyrus of the hippocampus. Both germinal centers
      exhibit an age-dependent decline in cell proliferation and neurogenesis, which
      may be associated with age-related decline in brain function. We recently
      identified the subcallosal zone (SCZ) as a novel neural stem cell niche with a
      potential to spontaneously produce new neuroblasts. We examined whether SCZ
      neurogenesis is also regulated by the age of mice. The number of newly generated
      neuroblasts was reduced in the SCZ with age, and only marginal number of DCX
      labeled neuroblasts was found in 6-month-old SCZ, which is most likely due to
      reduced proliferation of progenitor cells and loss of neural stem cells (NSCs).
      This age-dependent changes in the SCZ occurred earlier than that of other
      neurogenic brain regions. The neurosphere assay in vitro confirmed the depletion
      of NSCs within the SCZ of young adults. However, marked induction of neuroblast
      production in the SCZ was seen in 6-month-old mice after traumatic brain injury.
      Taken together, these results indicate that a rapid decline in SCZ neurogenesis
      in mice is due to depletion of NSCs and reduced capacity to produce neuroblasts.

PMID- 22417728
TI  - Sensory properties and instrumental texture analysis of chevon patties from
      intact male Boer and Kiko goats harvested at four endpoints.
AB  - Intact male Boer and Kiko goats (n=48) were harvested after 0, 4, 8, or 12 weeks
      on a 16% crude protein concentrate diet. Boneless goat carcass left sides were
      ground and formed into patties to evaluate cook loss, texture profile analysis,
      and descriptive sensory characteristics. Increasing feeding duration increased
      percent fat and decreased moisture in raw ground meat (P<0.05). Boer ground meat
      had more fat and less moisture than Kiko meat (P<0.05). Breed and feeding
      duration did not affect cook loss (P>0.05). Increased feeding duration increased
      aroma intensity and goaty, bloody, musty, and liver/organy aromas; salty, bitter,
      umami, grassy, goaty, fat, liver/organy, metallic, earthy, and chemical flavors;
      and juiciness and oiliness, while decreasing chewiness and crumbliness (P<0.05).
      Boer and Kiko patties had similar sensory properties after 0 and 4weeks on feed,
      but breeds were more distinguishable after 8 or 12 weeks on feed.

PMID- 22417729
TI  - Evolution of nitrate and nitrite during the processing of dry-cured ham with
      partial replacement of NaCl by other chloride salts.
AB  - Nitrate and nitrite are commonly added to dry-cured ham to provide protection
      against pathogen microorganisms, especially Clostridium botulinum. Both nitrate
      and nitrite were monitored with ion chromatography in dry-cured hams salted with
      different NaCl formulations (NaCl partially replaced by KCl and/or CaCl(2), and
      MgCl(2)). Nitrate, that is more stable than nitrite, diffuses into the ham and
      acts as a reservoir for nitrite generation. A correct nitrate and nitrite
      penetration was detected from the surface to the inner zones of the hams
      throughout its processing, independently of the salt formulation. Nitrate and
      nitrite achieved similar concentrations, around 37 and 2.2 ppm, respectively in
      the inner zones of the ham for the three assayed salt formulations at the end of
      the process, which are in compliance with European regulations.

PMID- 22417730
TI  - Biogenic amines content during extended ageing of dry-cured pork loins inoculated
      with probiotics.
AB  - The study determined the content of biogenic amines in dry-cured pork loins
      inoculated with Lactobacillus casei LOCK 0900 probiotic strain, in 4, 8 and 16
      month-old samples. Cadaverine, putrescine and tryptamine levels showed a time
      dependent increase during ageing. Histamine and spermidine were not detected.
      Spermine which was present at very low concentrations, tended to decrease.
      Cadaverine and tryptamine were the main biogenic amines at the end of the ageing
      period with average values of 39.6 mg/kg and 49.2 mg/kg respectively. The results
      were within the values reported for other dry-cured meat products and below the
      suggested toxic levels. The pH of samples increased significantly (p<0.05) with
      ageing time. The a(w) values decreased significantly (p<0.05) during ageing, with
      a mean value of 0.953+/-0.007 for samples aged for 4 months, and 0.852+/-0.007
      for samples aged for 16-months.

PMID- 22417731
TI  - Differences in lithium use patterns in the Netherlands: comparing middle-aged and
      older patients in a database study.
AB  - BACKGROUND: Age-dependent changes in lithium pharmacokinetic and pharmacodynamic
      properties can influence lithium use in an aging population, especially as newer
      treatment options are available. OBJECTIVE: We compared lithium use patterns
      between middle-aged and elderly outpatients in the Netherlands. METHODS: Data for
      this study were obtained from the Dutch PHARMO Record Linkage System. Incident
      lithium users 40 years or older were identified in the period 1996-2008. The
      following lithium use patterns were defined: continuation, add on, switch, and
      discontinuation. Differences were assessed for the following age groups: 40 to 49
      years, 50 to 59 years, 60 to 69 years, and 70 years or older. The youngest group
      was the reference group. Patient baseline characteristics and potential
      determinants of changes in lithium use patterns were assessed. RESULTS: We
      identified 2081 incident lithium users. Use of antidepressants was not different
      at baseline between age groups, but elderly patients starting lithium treatment
      used baseline antipsychotics less frequently (P < 0.05). Older patients were less
      likely to receive psychotropic drugs as add on to ongoing lithium therapy (P <
      0.05). Frequency of discontinuation and switch events did not differ between the
      age groups. In the whole study group, age was associated with any change in
      lithium use patterns. CONCLUSIONS: Older patients are less likely to receive
      psychotropic drugs as add on to ongoing lithium therapy. Despite pharmacokinetic
      and pharmacodynamic changes in the elderly, lithium is not more often
      discontinued and not more often switched in older patients.

PMID- 22417732
TI  - Evaluation of integrated registers for tuberculosis and HIV surveillance in
      children, Ethiopia, 2007-2009.
AB  - In 2008, Ethiopia implemented tuberculosis (TB) treatment registers that included
      columns for recording human immunodeficiency virus (HIV) test results (integrated
      registers) to replace the previous system of separate TB and HIV registers (pre
      integration registers). We compared the  proportion of children with documented
      HIV rapid test results at eight hospitals before and after adopting the
      integrated registers. HIV status was more consistently documented in the
      integrated registers; however, HIV status for infants aged <18 months could not
      be assessed, as the registers  did not capture results from polymerase chain
      reaction-based testing. Recording procedures should be revised to document age
      appropriate HIV diagnostic results and ensure referral for appropriate care.

PMID- 22417734
TI  - ROS signaling as common element in low oxygen and heat stresses.
AB  - The activation of the oxidative metabolism in plants under low oxygen conditions
      has prompted controversial views. The presence of a ROS component in the
      transcriptome in response to low oxygen has been observed and an overlap with
      heat stress has been proved. It has been also demonstrated that ROS are produced
      during both anoxia and heat, but the site of their production remain contentious.
      Membrane NADPH oxidase and mitochondrial electron transport flow have been
      indicated as possible ROS generation systems. Both anoxia and heat have been
      shown to induce the transcription of Heat Shock Factors (HSFs) and Heat Shock
      Proteins (HSPs), among which HSFA2 and some of its targets. HSFA2 over-expressing
      plant has been shown to be more tolerant to anoxia, while the knockout hsfa2 lose
      the capability of wild type plants to cross-acclimate to anoxia through mild heat
      pre-treatment. The production of ROS seems to be an integral part of the anoxia
      and heat response, where HSFs likely play a central role in activating the HSP
      pathway. This mechanism is suggested to result in enhanced plant tolerance to
      both anoxia and heat.

PMID- 22417733
TI  - Leaf ascorbic acid level--is it really important for ozone tolerance in rice?
AB  - Leaf ascorbic acid (ASA) level is thought to be an important trait conferring
      stress tolerance in plants, but definite evidence regarding its effectiveness in
      the breeding of stress tolerant crops is lacking. Therefore, the stress response
      of a rice TOS17 insertion mutant (ND6172) for a GDP-D-mannose-3',5'-epimerase
      gene, which is involved in ASA biosynthesis, was tested. Two fumigation
      experiments were conducted, in which rice plants (Oryza sativa L.) were exposed
      to (i) high ozone for ten days at the tillering stage (100 ppb, 7 h day-1); and
      (ii) to four different ozone concentrations ranging from charcoal filtered air to
      2.5 times the ambient concentration for the entire growth season. The mutant
      ND6172 had around 20-30% lower ASA level than the wild-type (Nipponbare), and
      exhibited a moderately higher level of visible leaf symptoms due to ozone
      exposure. Differences in ASA level between ND6172 and Nipponbare led to
      differential responses of the glutathione level, and the activities of
      glutathione reductase, ascorbate peroxidase, and dehydroascorbate reductase. With
      season-long ozone fumigation, yields and yield components were not negatively
      affected at ambient ozone level in both genotypes, but showed stronger decreases
      in ND6172 at higher ozone levels, especially at 2.5 times the ambient level.
      Similarly, the mature straw of ND6172 exhibited a higher degree of lignification
      at the 2.5 times ambient ozone level. In conclusion, a difference in leaf ASA
      level of around 20-30% is relevant for ozone tolerance in rice at levels
      exceeding the current ambient ozone concentrations.

PMID- 22417735
TI  - Cardiomyocyte size estimated from noninvasive measurements of left ventricular
      wall thickness and chamber diameter.
AB  - Noninvasive measurements of left ventricular wall thickness (LVT) and left
      ventricular chamber diameter (LVD) allow calculation of expected left ventricular
      weight (LVW), but not of myocyte breadth (MyB), so that specification of left
      ventricular hypertrophy (LVH) is not optimal. Hypertrophied hearts, excluding
      coronary heart disease, and comparison specimens without hypertrophy were
      compiled into a series of 78 forensic autopsies, wherein LVT, LVD, and LVW were
      measured. MyB was measured in hematoxylin and eosin-stained paraffin sections. A
      series of clinical cases tabulating LVD and LVT was assembled from readily
      available publications. From postmortem data, a regression equation was derived
      to predict MyB from LVD and LVT. Applying this equation to the clinical data
      produced a scatter plot closely resembling that in the postmortem dataset. The
      equation derived here appears to provide valid predictions of cardiomyocyte sizes
      expected in histological measurements. The finding is the first of its kind and
      requires further testing for validation or rejection. This is offered as a
      provisional way to improve the determination of LVH using noninvasive
      measurements. How this improvement might enhance understanding of the mechanisms
      for hypertrophy is briefly explored, thus generating working hypotheses.

PMID- 22417736
TI  - Causes of hyperferritinaemia classified by HIV status in a tertiary-care setting
      in South Africa.
AB  - This study included all patients, with known HIV-1 status, admitted to hospital
      over a 5-year period with serum ferritin values exceeding 1500 MUg/l. Markedly
      elevated serum ferritin levels are associated with a host of causes which poses a
      diagnostic dilemma, as the aetiology is often highly dependent on local
      epidemiology. We evaluated patients' records retrospectively to determine
      underlying causes of possible hyperferritinaemia. Aetiologies associated with
      hyperferritinaemia varied significantly depending on HIV-1 status. In patients
      infected with the HIV-1 virus, infectious causes predominated with Mycobacterium
      tuberculosis accounting for more than 50% of the patient population with an odds
      ratio of 17.98 (95% confidence interval 8.31-38.88) in HIV-positive compared to
      HIV-negative patients. Of the HIV-1-negative patients, hereditary
      haemochromatosis accounted for less than 2% of patients and chronic renal failure
      was the most common diagnosis. The finding of hyperferritinaemia should prompt
      determination of HIV-1 status, as this impacts significantly on aetiological
      epidemiology. In HIV-1-positive patients, aggressive investigation for
      mycobacterial infection should be undertaken in cases of combined
      hyperferritinaemia and positive HIV-1 serology.

PMID- 22417737
TI  - Unexpectedly high prevalence of sarcoidosis in a representative U.S. Metropolitan
      population.
AB  - The prevalence of sarcoidosis in the United States is unknown, with estimates
      ranging widely from 1 to 40 per 100,000. We sought to determine the prevalence of
      sarcoidosis in our health system compared to other rare lung diseases and to
      further establish if the prevalence was changing over time. We interrogated the
      electronic medical records of all patients treated in our health system from 1995
      to 2010 (1.48 million patients) using the common ICD9 codes for sarcoidosis
      (135), lung cancer (162), and several other lung diseases characterized, like
      sarcoidosis, as "rare lung diseases". The patient demographic information (race,
      gender, age) was further analyzed to identify signature data patterns. The
      prevalence of sarcoidosis in our health system increased steadily from
      164/100,000 in 1995 to 330/100,000 in 2010, and this trend could not be ascribed
      simply to changes in patient demographics or patient referral patterns. We
      further estimate that the prevalence of sarcoidosis exceeds 48 per 100,000 in
      Franklin County, Ohio, the demographic profile of which is nearly identical to
      that of the U.S. Sarcoidosis prevalence increased over time relative to lung
      cancer, a benchmark disease with stable disease prevalence, and exceeded that of
      other rare lung diseases. We postulate that the observed 2-fold increase in
      sarcoidosis disease prevalence in our health system is primarily related to
      improved detection and diagnostic approaches, and we conclude that the actual
      prevalence of sarcoidosis in central Ohio greatly exceeds current U.S. estimates.

PMID- 22417738
TI  - Efficacy and safety of convex probe EBUS-TBNA in sarcoidosis: a systematic review
      and meta-analysis.
AB  - BACKGROUND AND AIM: Real-time endobronchial ultrasound-guided transbronchial
      needle aspiration (EBUS-TBNA) is a minimally invasive technique for diagnosis of
      mediastinal lymphadenopathy. Although most studies have reported the utility of
      EBUS-TBNA in malignancy, its use has been extended to benign conditions including
      sarcoidosis. Herein, we perform a systematic review and meta-analysis of studies
      reporting the diagnostic yield and safety of EBUS-TBNA in sarcoidosis. METHODS:
      We searched the PubMed and EmBase databases for relevant studies published from
      2004 to 2011, and included studies that have reported the diagnostic yield of
      EBUS-TBNA in sarcoidosis. The quality of studies was assessed using the QualSyst
      tool. We calculated the proportions with 95% confidence interval (CI) to assess
      the diagnostic yield of EBUS-TBNA in individual studies and then pooled the
      results using a random effects model. Heterogeneity was assessed using the I(2)
      and Cochran-Q tests while publication bias was assessed using both graphical and
      statistical methods. RESULTS: Our search yielded 15 studies (553 patients of
      sarcoidosis). The diagnostic yield of EBUS-TBNA ranged from 54 to 93% with the
      pooled diagnostic accuracy being 79% (95% CI, 71-86%) by the random effects
      model. The yield was not statistically different in studies employing on-site
      cytological evaluation (80.1%) vs. those without (81.3%). However, the diagnostic
      yield was significantly higher in prospective studies (83.9%) vs. the
      retrospective studies (74.3%). Only five minor complications were reported in 553
      patients. There was evidence of heterogeneity and publication bias. CONCLUSIONS:
      EBUS-TBNA is a safe and efficacious procedure in the diagnosis of sarcoidosis,
      and should be routinely employed wherever available.

PMID- 22417739
TI  - Hydrochemical characteristics and water quality assessment of surface water and
      groundwater in Songnen plain, Northeast China.
AB  - Water quality is the critical factor that influence on human health and quantity
      and quality of grain production in semi-humid and semi-arid area. Songnen plain
      is one of the grain bases in China, as well as one of the three major
      distribution regions of soda saline-alkali soil in the world. To assess the water
      quality, surface water and groundwater were sampled and analyzed by fuzzy
      membership analysis and multivariate statistics. The surface water were gather
      into class I, IV and V, while groundwater were grouped as class I, II, III and V
      by fuzzy membership analysis. The water samples were grouped into four categories
      according to irrigation water quality assessment diagrams of USDA. Most water
      samples distributed in category C1-S1, C2-S2 and C3-S3. Three groups were
      generated from hierarchical cluster analysis. Four principal components were
      extracted from principal component analysis. The indicators to water quality
      assessment were Na, HCO(3), NO(3), Fe, Mn and EC from principal component
      analysis. We conclude that surface water and shallow groundwater are suitable for
      irrigation, the reservoir and deep groundwater in upstream are the resources for
      drinking. The water for drinking should remove of the naturally occurring ions of
      Fe and Mn. The control of sodium and salinity hazard is required for irrigation.
      The integrated management of surface water and groundwater for drinking and
      irrigation is to solve the water issues.

PMID- 22417740
TI  - River eutrophication: irrigated vs. non-irrigated agriculture through different
      spatial scales.
AB  - The main objective of this study was to determine how spatial scale may affect
      the results when relating land use to nutrient enrichment of rivers and,
      secondly, to investigate which agricultural practices are more responsible for
      river eutrophication in the study area. Agriculture was split into three
      subclasses (irrigated, non-irrigated and low-impact agriculture) which were
      correlated to stream nutrient concentration on four spatial scales: large scale
      (drainage area of total subcatchment and 100 m wide subcatchment corridors) and
      local scale (5 and 1 km radius buffers). Nitrate, ammonium and orthophosphate
      concentrations and land use composition (agriculture, urban and forest) were
      measured at 130 river reaches in south-central Spain during the 2001-2009 period.
      Results suggested that different spatial scales may lead to different
      conclusions. Spatial autocorrelation and the inadequate representation of some
      land uses produced unreal results on large scales. Conversely, local scales did
      not show data autocorrelation and agriculture subclasses were well represented.
      The local scale of 1 km buffer was the most appropriate to detect river
      eutrophication in central Spanish rivers, with irrigated cropland as the main
      cause of river pollution by nitrate. As regards river management, a threshold of
      50% irrigated cropland within a 1 km radius buffer has been obtained using
      breakpoint regression analysis. This means that no more than 50% of irrigation
      croplands should be allowed near river banks in order to avoid river
      eutrophication. Finally, a methodological approach is proposed to choose the
      appropriate spatial scale when studying river eutrophication caused by diffuse
      pollution like agriculture.

PMID- 22417741
TI  - Sequential treatment of PTA wastewater in a two-stage UASB process: focusing on p
      toluate degradation and microbial distribution.
AB  - Two-stage upflow anaerobic sludge blanket (UASB) process was investigated as an
      efficient process configuration option for the treatment of purified terephthalic
      acid (PTA) wastewater. To study its feasibility in a defined condition, synthetic
      wastewater containing only the major pollutants (i.e., acetate, benzoate,
      terephthalate and p-toluate) was used. By focusing the role of the second stage
      on the p-toluate degradation, improved overall COD and p-toluate removal
      capacities of 4.18 and 1.35 g-thCOD/L.day could be achieved together with a
      complete COD removal efficiency. In this situation, all the pollutants except p
      toluate were completely degraded in the first stage while 38 and 62% of p-toluate
      originally present in the wastewater were consecutively degraded in the
      individual stages. The concomitant methane production rate in each stage was 0.91
      and 0.35 L/L.day respectively, and the methane yield on p-toluate was determined
      to be 0.12 L/g-thCOD. Batch tests using the granules obtained from each stage
      revealed that the acidogenic microorganisms enriched in both stages had a
      universal ability to degrade all aromatic pollutants present in the PTA
      wastewater. Moreover, image analysis using scanning electron microscope and
      confocal laser scanning microscopy combined with fluorescence in situ
      hybridization technique elucidated that the distribution of acidogens and
      methanogens within the granule was varied in each stage, which influenced the
      mass transfer regime resulting in the different pollutant degradation rates
      during the batch tests.

PMID- 22417742
TI  - Investigation of the degradation of cresols in the treatments with ozone.
AB  - The reaction between ozone and the three cresol isomers was investigated in pure
      water. Cresols were selected as model substrates representing an important
      component of humic material. Cresols carry both a hydroxyl and a methyl group,
      each theoretically increasing the reactivity of ozone with the aromatic ring.
      Direct comparison of the aromatic ring and the methyl group reactivities was made
      possible by the analysis of reaction products. The substrate degradation kinetics
      was studied by preparing aqueous solutions of each cresol and treating them with
      ozone for increasing time periods. It had been hypothesized that
      hydroxybenzaldehydes and hydroxybenzoic acids could be possible degradation
      intermediates of cresols. To verify this hypothesis, the degradation kinetics of
      three hydroxybenzaldehydes and two hydroxybenzoic acids were also studied. The
      reaction products were studied using gas chromatography (GC)-electron capture
      negative ionization (ECNI)-mass spectrometry (MS) analysis after direct
      derivatization of the samples with 5-chloro-2,2,3,3,4,4,5,5-octafluoro-1-pentyl
      chloroformate (ClOFPCF). This new analytical approach enables the extraction and
      analysis of highly polar polycarboxylic and hydroxycarboxylic acids, as well as
      highly polar aldehydes and hydroxy aldehydes that are difficult to extract and
      measure using conventional methods. As such, this new approach offered insights
      into ozone reaction intermediates that had been previously hypothesized, but not
      confirmed. Several highly hydrophilic degradation intermediates were identified,
      including malic, citraconic, itaconic, malonic, methylmuconic, and tartronic
      acid, but no hydroxybenzaldehydes were observed. The results support a 3-stage
      mechanism previously hypothesized, which involves ring-opening of the phenolic
      group, followed by the generation of several intermediates of increasing
      oxidation state, finally leading to relatively stable products, such as malonic
      and oxalic acids. We demonstrated that oxidation of the methyl group does not
      occur during cresol degradation.

PMID- 22417743
TI  - Functional role of IL-22 in psoriatic arthritis.
AB  - INTRODUCTION: Interleukin-22 (IL-22) is a cytokine of IL-10 family with
      significant proliferative effect on different cell lines. Immunopathological role
      of IL-22 has been studied in rheumatoid arthritis (RA) and psoriasis. Here we are
      reporting the functional role of IL-22 in the inflammatory and proliferative
      cascades of psoriatic arthritis (PsA). METHOD: From peripheral blood and synovial
      fluid (SF) of PsA (n = 15), RA (n = 15) and osteoarthritis (OA, n = 15) patients,
      mononuclear cells were obtained and magnetically sorted for CD3+ T cells.
      Fibroblast like synoviocytes (FLS) were isolated from the synovial tissue of PsA
      (n = 5), RA (n = 5) and OA (n = 5) patients. IL-22 levels in SF and serum were
      measured by enzyme linked immunosorbent assay (ELISA). Proliferative effect of
      human recombinant IL-22 (rIL-22) on FLS was assessed by MTT (3-(4, 5
      Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a yellow tetrazole) and
      CFSE dilution (Carboxyfluorescein succinimidyl ester) assays. Expression of IL
      22Ralpha1 in FLS was determined by western blot. RESULTS: IL-22 levels were
      significantly elevated in SF of PsA patients (17.75 +/- 3.46 pg/ml) compared to
      SF of OA (5.03 +/- 0.39 pg/ml), p < 0.001. In MTT and CFSE dilution assays, rIL
      22 (MTT, OD: 1.27 +/- 0.06) induced significant proliferation of FLS derived from
      PsA patients compared to media (OD: 0.53 +/- 0.02), p < 0.001. In addition, rIL
      22 induced significantly more proliferation of FLS in presence of TNF-alpha. IL
      22Ralpha1 was expressed in FLS of PsA, RA and OA patients. Anti IL-22R antibody
      significantly inhibited the proliferative effect of rIL-22. Further we
      demonstrated that activated synovial T cells of PsA and RA patients produced
      significantly more IL-22 than those of OA patients. CONCLUSION: SF of PsA
      patients have higher concentration of IL-22 and rIL-22 induced marked
      proliferation of PsA derived FLS. Moreover combination of rIL-22 and TNF-alpha
      showed significantly more proliferative effect on FLS. IL-22Ralpha1 was expressed
      in FLS. Successful inhibition of IL-22 induced FLS proliferation by anti IL-22R
      antibody suggests that blocking of IL-22/IL-22R interaction may be considered as
      a novel therapeutic target for PsA.

PMID- 22417744
TI  - Structure and properties of noncrystalline nano-Al(OH)3 reclaimed from carbonized
      residual wastewater treatment sludge.
AB  - Performance of wastewater treatement sludge-carbon (SC) can be evidently improved
      by removing the inorganic fractions. A novel investigation for recovery of Al
      from acid leaching of SC and synthesis of nano-Al(OH)(3) has been conducted.
      Results show that the sodium aluminates with high purity can be obtained by
      effectively dissolving the inorganic fractions from SC and by further removing
      the impurities (Fe(3+), Ca(2+), Mg(2+), S(4+), and P(3+)). Highly dispersed
      Al(OH)(3) with high S(BET) is obtained at pH = 6. The peaks of -CH(2)- vibration
      and the C1s peaks (binding energies of 284.6 eV) imply that polyethylene glycol
      1000 (PEG-1000) is chemically adsorbed on the surface of Al(OH)(3) samples, which
      is propitious to reduce the hydrogen bonds between water molecules and surface 
      OH groups to prevent hard agglomeration. The stretching vibration peaks of
      [AlO(2)](-) and the Na1s peaks confirm that a trace of sodium aluminate
      (NaAl(OH)(4), Na(+)(H(2)O)(4)[Al(OH)(4)(-)], or the dehydrated monomers) is
      retained in the prepared Al(OH)(3). The main phase transformation for calcination
      (<=800  degrees C) of the SC-derived Al(OH)(3) is from amorphous Al(OH)(3) to
      amorphous A1(2)O(3). Here we highlight that production of Al(OH)(3) and SC from
      sludge provides the potential application in significant quantities that can
      revolutionize the handling of such kinds of harmful waste.

PMID- 22417745
TI  - Simultaneous occurrence of distantly located multiple sebaceous carcinomas with
      elevated serum TGF-beta in Muir-Torre syndrome.

PMID- 22417747
TI  - Antioxidant and bioenergetic coupling between neurons and astrocytes.
AB  - Oxidative and nitrosative stress underlie the pathogenesis of a broad range of
      human diseases, in particular neurodegenerative disorders. Within the brain,
      neurons are the cells most vulnerable to excess reactive oxygen and nitrogen
      species; their survival relies on the antioxidant protection promoted by
      neighbouring astrocytes. However, neurons are also intrinsically equipped with a
      biochemical mechanism that links glucose metabolism to antioxidant defence.
      Neurons actively metabolize glucose through the pentose phosphate pathway, which
      maintains the antioxidant glutathione in its reduced state, hence exerting
      neuroprotection. This process is tightly controlled by a key glycolysis-promoting
      enzyme and is dependent on an appropriate supply of energy substrates from
      astrocytes. Thus brain bioenergetic and antioxidant defence is coupled between
      neurons and astrocytes. A better understanding of the regulation of this
      intercellular coupling should be important for identifying novel targets for
      future therapeutic interventions.

PMID- 22417748
TI  - Replication fork dynamics and the DNA damage response.
AB  - Prevention and repair of DNA damage is essential for maintenance of genomic
      stability and cell survival. DNA replication during S-phase can be a source of
      DNA damage if endogenous or exogenous stresses impair the progression of
      replication forks. It has become increasingly clear that DNA-damage-response
      pathways do not only respond to the presence of damaged DNA, but also modulate
      DNA replication dynamics to prevent DNA damage formation during S-phase. Such
      observations may help explain the developmental defects or cancer predisposition
      caused by mutations in DNA-damage-response genes. The present review focuses on
      molecular mechanisms by which DNA-damage-response pathways control and promote
      replication dynamics in vertebrate cells. In particular, DNA damage pathways
      contribute to proper replication by regulating replication initiation,
      stabilizing transiently stalled forks, promoting replication restart and
      facilitating fork movement on difficult-to-replicate templates. If replication
      fork progression fails to be rescued, this may lead to DNA damage and genomic
      instability via nuclease processing of aberrant fork structures or incomplete
      sister chromatid separation during mitosis.

PMID- 22417750
TI  - Epithelial-mesenchymal interaction during UVB-induced up-regulation of neutral
      endopeptidase.
AB  - We recently reported that overexpression of the elastase NEP (neutral
      endopeptidase) by fibroblasts plays a pivotal role in the mechanism of UVB
      induced skin wrinkling by degrading dermal elastic fibres. Since UVB does not
      penetrate to the dermis, we hypothesized that factors secreted by UVB-exposed
      keratinocytes in the epidermis trigger fibroblasts in the dermis to increase
      their expression of NEP which then degrades the elastic fibres. In the present
      study, we characterized the epithelial-mesenchymal interaction between
      keratinocytes and fibroblasts which leads to increased expression of NEP. Human
      fibroblasts co-cultured with UVB-exposed human keratinocytes in cell inserts
      significantly increased their expression of NEP at the transcriptional,
      translational and enzymatic levels. Neutralizing antibodies to IL (interleukin)
      1alpha or GM-CSF (granulocyte/macrophage colony-stimulating factor) significantly
      abolished the increased expression of NEP at the enzymatic levels in human
      fibroblasts co-cultured with UVB-exposed human keratinocytes, whereas
      neutralizing antibodies to IL-6, IL-8 or TNFalpha (tumour necrosis factor alpha)
      had no such effect. The addition of IL-1alpha or GM-CSF, but not TNFalpha, IL-6
      or IL-8, at concentrations ranging from 1 to 10 nM, significantly stimulated the
      expression of NEP in human fibroblasts at the transcriptional and translational
      levels. These findings suggest that IL-1alpha and GM-CSF are intrinsic cytokines
      secreted by UVB-exposed keratinocytes that stimulate expression of NEP by
      fibroblasts.

PMID- 22417749
TI  - The yeast vacuolar Rab GTPase Ypt7p has an activity beyond membrane recruitment
      of the homotypic fusion and protein sorting-Class C Vps complex.
AB  - A previous report described lipid mixing of reconstituted proteoliposomes made
      using lipid mixtures that mimic the composition of yeast vacuoles. This lipid
      mixing required SNARE {SNAP [soluble NSF (N-ethylmaleimide-sensitive factor)
      attachment protein] receptor} proteins, Sec18p and Sec17p (yeast NSF and alpha
      SNAP) and the HOPS (homotypic fusion and protein sorting)-Class C Vps (vacuole
      protein sorting) complex, but not the vacuolar Rab GTPase Ypt7p. The present
      study investigates the activity of Ypt7p in proteoliposome lipid mixing. Ypt7p is
      required for the lipid mixing of proteoliposomes lacking cardiolipin [1,3-bis-(sn
      3'-phosphatidyl)-sn-glycerol]. Omission of other lipids with negatively charged
      and/or small head groups does not cause Ypt7p dependence for lipid mixing. Yeast
      vacuoles made from strains disrupted for CRD1 (cardiolipin synthase) fuse to the
      same extent as vacuoles from strains with functional CRD1. Disruption of CRD1
      does not alter dependence on Rab GTPases for vacuole fusion. It has been proposed
      that the recruitment of the HOPS complex to membranes is the main function of
      Ypt7p. However, Ypt7p is still required for lipid mixing even when the
      concentration of HOPS complex in lipid-mixing reactions is adjusted such that
      cardiolipin-free proteoliposomes with or without Ypt7p bind to equal amounts of
      HOPS. Ypt7p therefore must stimulate membrane fusion by a mechanism that is in
      addition to recruitment of HOPS to the membrane. This is the first demonstration
      of such a stimulatory activity--that is, beyond bulk effector recruitment--for a
      Rab GTPase.

PMID- 22417754
TI  - The functional assessment of patients with pulmonary multidrug-resistant
      tuberculosis.
AB  - BACKGROUND: Tuberculosis (TB) remains an important public health problem
      worldwide, as its residual lesions result in functional and quality of life
      impairments. Few studies have investigated multiple-drug-resistant pulmonary TB
      (MDR-TB), and the literature regarding the functional  parameters of this group
      of patients is scarce. Functional characterization may point to the need for post
      treatment intervention measures that optimize the quality of life in patients
      with MDR-TB. Thus, this study sought to analyze the respiratory function,
      functional capacity, and quality  of life of patients who were treated for MDR
      pulmonary TB. METHODS: This study investigated a cross-sectional cohort of MDR-TB
      patients who underwent drug treatment for at least 18 months. Patients who had
      associated diseases (human immunodeficiency virus [HIV], severe heart disease,
      and hypertension)  or disabilities that prevented them from walking were
      excluded. The subjects underwent the following assessments: forced spirometry, a
      chest radiograph, the 6-min walk test, a bioelectrical impedance analysis,
      maximal inspiratory and expiratory pressures, and a health-related quality of
      life  questionnaire. RESULTS: Eighteen patients who met the eligibility criteria
      were enrolled. Spirometric evaluation showed that 78% of the subjects had
      abnormal patterns. The maximal respiratory pressures were significantly decreased
      in all subjects, despite the fact that their nutritional status  was within the
      normal range. The distance completed in the 6-min walk test was less than
      expected in 72% of the subjects. All of the subjects who were evaluated had
      residual lesions, and 78% reported a worsening in their quality of life.
      CONCLUSIONS: In conclusion MDR-TB cured subjects exhibit  impaired respiratory
      function and a mildly reduced functional capacity and quality of life, suggesting
      that a portion of these patients may require a pulmonary rehabilitation approach.

PMID- 22417755
TI  - 'Let men into the pregnancy'--men's perceptions about being tested for chlamydia
      and HIV during pregnancy.
AB  - OBJECTIVE: to investigate how to prevent transmission of HIV and Chlamydia
      trachomatis (CT) by exploring whether screening of men during pregnancy may be an
      innovative way to reach men, to increase detection, and to avoid the present
      gendered responsibility. DESIGN: an explorative research strategy with in-depth
      interviews and an analysis informed by grounded theory principles was used.
      SETTING: the northern part of Sweden. PARTICIPANTS: twenty men/becoming fathers
      in their twenties and early thirties were offered CT and HIV testing and were
      interviewed about their perceptions about being tested during pregnancy.
      FINDINGS: Six categories emerged that concerned the men's risk perceptions,
      reasons for not testing men, benefits and negative consequences associated with
      being tested, incentive measures for reaching men and the optional time for
      testing men during pregnancy. The majority of the men perceived their own risk
      for having CT or HIV to be close to zero, trusted their stable partner, and did
      not see men as transmitters. They did not understand how men could play a role in
      CT or HIV transmission or how these infections could negatively affect the child.
      However, few informants could see any logical reasons for excluding men from
      testing and the majority was positive towards screening men during the pregnancy.
      KEY CONCLUSIONS: men's sexual health and behaviour on social and biological
      grounds will affect the health of women and their children during pregnancy and
      childbirth. As long as expectant fathers do not count in this 'triad', there is a
      risk that CT and HIV infections in adults and infants will continue to be an
      unsolved problem. IMPLICATIONS FOR PRACTICE: knowledge from this research can
      contribute to influencing the attitudes among health-care providers positively,
      and inspiring policy changes.

PMID- 22417756
TI  - The Edinburgh Postnatal Depression Scale: translation and antepartum validation
      for a Hungarian sample.
AB  - OBJECTIVE: the Edinburgh Postnatal Depression Scale (EPDS) is an important
      screening instrument routinely used during the peripartum period for the
      identification of depression. The purpose of the study was to assess the validity
      of the 10-item EPDS in screening for antepartum depression (APD) in Hungary.
      DESIGN: validation study carried out between July and December 2010. SETTING:
      Department of Obstetrics and Gynecology, University of Szeged, Hungary.
      PARTICIPANTS: 219 women attending a routine check-up at 12 weeks antepartum.
      INTERVENTIONS: participants completed the newly translated Hungarian version of
      the EPDS and underwent a clinical assessment with the Structured Clinical
      Interview for DSM-IV disorders (SCID-I). MEASUREMENT AND FINDINGS: seven (3.2%)
      of the mothers were diagnosed with major antepartum depression and 15 persons
      (6.85%) with minor depression on the basis of the SCID. Internal consistency of
      the EPDS was satisfactory (Cronbach alpha coefficients >=0.728). The best cut-off
      on the Hungarian version of the EPDS for major depression was 8/9, with a
      sensitivity of 71.4%, and a specificity of 91.5%. The area under the ROC curve
      was found significant for combined depression as well and at a cut-off of 6/7
      indicated a sensitivity of 81.8% and a specificity of 83.2%. KEY CONCLUSIONS: the
      EPDS showed acceptable validity despite a considerable scatter in the total
      scores in our sample. IMPLICATION FOR PRACTICE: the EPDS is a reliable instrument
      for the screening of depressive disorders, especially major depressive disorder
      in early pregnancy among Hungarian women.

PMID- 22417757
TI  - The professionalising of breast feeding--where are we a decade on?
AB  - This paper is an empirically informed opinion piece revisiting an argument
      published in Midwifery 10 years ago, that the increasing professionalisation of
      breast feeding was not supporting women in Australia in sustaining breast
      feeding. We present the last 10 years of primary research on the topic, explore
      major policy initiatives and the establishment and growth of lactation
      consultants in Australia to see if this has made a difference to sustained rates
      of breast feeding. We present an analysis of the only consistently collected
      national statistics on breast feeding and compare this with national and state
      level government data collections from the last decade. We have found that the
      considerable effort invested in trying to improve duration of breast feeding
      amongst women in Australia appears to have failed to improve sustained breast
      feeding rates. We argue that this situation might be related to losing sight of
      the embodied nature of breast feeding and the relationships that must exist
      between the mother and baby, the knowledge and skills women quickly develop, and
      a loss of woman to woman support. We conclude that midwives have a major role in
      avoiding us reproducing similar, unintended, negative consequences to those
      resulting from increasing obstetrician managed normal birth. These include
      midwifery scrutiny and involvement in policy development and institutional
      practices and the design of services.

PMID- 22417758
TI  - Empathy in sexually sadistic offenders: an experimental comparison with non
      sadistic sexual offenders.
AB  - Previous studies suggest that severe sexual sadism and psychopathy are
      phenotypically different, although both are characterized by deficits in
      emotional processing. We assessed empathic capacity in a sample of 12 sexual
      sadists in comparison with 23 non-sadistic offenders using the Multifaceted
      Empathy Test (MET). All participants were forensic patients under mandatory
      treatment orders who had committed sexual offenses. The MET is a computerized
      rating task that differentiates and measures cognitive and emotional components
      of empathy, or perspective-taking versus compassionate components. To identify
      the effects of possible empathy deficits caused by psychopathic traits, we
      controlled both samples for psychopathy as a covariate, measured by the
      Psychopathy Checklist-Revised (PCL-R). According to our results, sexual sadists
      did not differ from non-sadistic sexual offenders with regard to emotional
      empathy for either positive or negative stimuli. The results suggest that severe
      sexual sadism is a distinct, pathological sexual arousal response, not a deficit
      in emotional processing.

PMID- 22417759
TI  - Predicting discharge in forensic psychiatry: the legal and psychosocial factors
      associated with long and short stays in forensic psychiatric hospitals.
AB  - In Germany, both the number of patients treated in forensic psychiatric hospitals
      and the average inpatient treatment period have been increasing for over thirty
      years. Biographical and clinical factors, e.g., the number of prior offences,
      type of offence, and psychiatric diagnosis, count among the factors that
      influence the treatment duration and the likelihood of discharge. The aims of the
      current study were threefold: (1) to provide an estimate of the German forensic
      psychiatric patient population with a low likelihood of discharge, (2) to
      replicate a set of personal variables that predict a relatively high, as opposed
      to a low, likelihood of discharge from forensic psychiatric hospitals, and (3) to
      describe a group of other factors that are likely to add to the existing body of
      knowledge. Based on a sample of 899 patients, we applied a battery of primarily
      biographical and other personal variables to two subgroups of patients. The first
      subgroup of patients had been treated in a forensic psychiatric hospital
      according to section 63 of the German legal code for at least ten years (long
      stay patients, n=137), whereas the second subgroup had been released after a
      maximum treatment period of four years (short-stay patients, n=67). The resulting
      logistic regression model had a high goodness of fit, with more than 85% of the
      patients correctly classified into the groups. In accordance with earlier
      studies, we found a series of personal variables, including age at first
      admission and type of offence, to be predictive of a short or long-stay. Other
      findings, such as the high number of immigrants among the short-stay patients and
      the significance of a patient's work time before admission to a forensic
      psychiatric hospital, are more clearly represented than has been observed in
      previous research.

PMID- 22417760
TI  - Transcription of genes involved in glutathione biosynthesis in the solitary
      tunicate Ciona intestinalis exposed to metals.
AB  - Exposure to metals is known to generate oxidative stress risk in living
      organisms, which are able to respond with the induction of antioxidant defenses,
      both enzymatic and non-enzymatic. Glutathione (GSH) is considered to be an
      important cellular component involved in protecting cells, both as metal
      chelating agent and oxygen radical scavenger. In this work we used molecular
      techniques to analyze the nucleotide and predicted amino acid sequences of genes
      involved in GSH biosynthesis, gamma-glutamyl-cysteine ligase catalytic subunit
      (ci-gclc), gamma-glutamyl-cysteine ligase modifier subunit (ci-gclm) and GSH
      synthase (ci-gs) in the solitary tunicate Ciona intestinalis. We also studied the
      transcription of the above genes after in vivo exposure to Cd, Cu and Zn by
      semiquantitativ RT-PCR to improve our knowledge about the relationship between
      metal-induced oxidative stress and GSH production and locate mRNA expression by
      in situ hybridization (ISH). These genes exhibit a good level of sequence
      conservation with metazoan homologs generally, especially for residues important
      for the activity of the enzymes. Phylogenetic analyses indicate that the three
      enzymes evolved in different ways, Ci-GCLC and Ci-GS being mostly correlated with
      invertebrate proteins, Ci-GCLM being as sister group of vertebrate GCLMs. Our in
      silico analyses of the ci-gs and ci-gclc promoter regions revealed putative
      consensus sequences similar to mammalian metal-responsive elements (MRE) and
      antioxidant response elements (ARE), indicating that the transcription of these
      genes may directly depend on metals and/or reactive oxygen species. Results
      highlight a statistically significant increase in gene transcription,
      demonstrating that metal treatments have inducible effects on these genes. They
      can modulate gene transcription not only through MREs but also through AREs, as a
      consequence of metal-dependent ROS formation. The ISH location of Ci-GS and Ci
      GCLC mRNAs shows that the cells most involved in glutathione biosynthesis are
      circulating hemocytes. The data presented here emphasize the importance of
      complex metal regulation of ci-gclc, ci-gclm and ci-gs transcription, which can
      create an efficient detoxification pathway allowing C. intestinalis to survive in
      continued elevated presence of metals in the environment.

PMID- 22417761
TI  - Contrasting mercury accumulation patterns in tilapia (Oreochromis niloticus) and
      implications on somatic growth dilution.
AB  - Dietary ingestion constitutes a major pathway for mercury (Hg) accumulation in
      freshwater fish, thus the ingestion rate (IR) may greatly influence the Hg
      bioaccumulation through its effect on Hg influx and other biokinetic processes.
      To explore the complex influence of IR, we conducted long-term bioaccumulation
      experiments by accurately controlling the IRs in the freshwater tilapia
      (Oreochromis niloticus). The dietary accumulation of both inorganic mercury
      (Hg[II]) and methylmercury (MeHg) in tilapia under different IRs was monitored
      over a period of 30 days by feeding the fish with uniformly radiolabeled
      crustaceans. The biokinetic parameters under various IRs were concurrently
      determined. With the increase of IR from 0.01 g g-1 d-1 to 0.12 g g-1 d-1, the
      dietary assimilation efficiency of Hg(II) in the tilapia decreased by 43% while
      the elimination rate increased by a factor of 1.8; both biokinetic changes slowed
      down the overall Hg(II) bioaccumulation at high IRs. In contrast to Hg(II), the
      biokinetics of MeHg was not significantly influenced, but its bioaccumulation
      increased disproportionally with increasing IR, showing slower increase at higher
      IR. We then employed a biokinetic model to simulate the long-term mercury
      bioaccumulation patterns in tilapia at various IRs. The modeling results
      indicated that the growth effect could not be ignored in long-term accumulation
      process. A rapid growth of fish driven by food availability could significantly
      reduce the MeHg concentrations in the tilapia. Our results demonstrated for the
      first time the contrasting influences of dietary ingestion on the long-term
      bioaccumulation of Hg(II) and MeHg. The somatic growth dilution was much more
      likely to occur for MeHg than for Hg(II).

PMID- 22417762
TI  - Antioxidative defense and oxidative stress in ringed seals (Pusa hispida) from
      differently polluted areas.
AB  - High contaminant levels detected in Baltic seals have been associated with
      various health effects. In this study several parameters related to antioxidative
      defense and oxidative stress (concentrations of reduced and oxidised glutathione,
      lipid hydroperoxide and vitamin E, activities of glutathione reductase,
      peroxidase and S-transferase, glucose-6-phosphate dehydrogenase, catalase, and
      superoxidedismutase) were measured in the livers of ringed seals from the Baltic
      Sea and from a less contaminated reference area, Svalbard, Norway. Seals were
      caught during two different time periods 1996-1997 and 2002-2007, which represent
      different levels of contamination. No signs of oxidative damage were found in the
      Baltic seals. However, glutathione metabolism was enhanced in the ringed seals
      from the Baltic Sea compared to the seals from Svalbard. The adaptation to dive
      where repetitive ischemia/reperfusion occurs naturally may contribute to the
      resistance of oxidative stress and to the capacity to increase enzymatic
      antioxidant defense in phocid seals. This could explain the similarities in
      oxidative stress levels despite the differences in antioxidant responses between
      the ringed seals from the Baltic Sea and Svalbard.

PMID- 22417763
TI  - Metabolism of polybrominated diphenyl ethers and tetrabromobisphenol A by fish
      liver subcellular fractions in vitro.
AB  - Polybrominated diphenyl ethers (PBDEs) and tetrabromobisphenol A (TBBPA) are two
      major flame retardants that accumulate in fish tissues and are potentially toxic.
      Their debrominated and oxidated derivatives were also reported in fish tissues
      although the sources of theses derivatives were unidentified. Our study was to
      determine whether PBDEs and TBBPA could be metabolized by fish liver subcellular
      fractions in vitro and to identify what types of metabolites were formed. Liver
      microsomes and S9 fractions of crucian carp (Carassius auratus) were exposed to
      4,4'-dibromodiphenyl ether (BDE 15), 2,2',4,4'-tetrabromodiphenyl ether (BDE 47)
      or TBBPA solutions for 4h. Exposure of liver subcellular fractions to BDE 15
      resulted in the formation of bromophenol and two monohydroxylated dibromodiphenyl
      ether metabolites. Neither in microsomes nor in S9 studies has revealed the
      presence of hydroxylated metabolites with BDE 47 exposure which indicated that
      the oxidation reactions in vitro were hindered by the increased number of bromine
      substituents on the PBDEs. TBBPA underwent an oxidative cleavage near the central
      carbon of the molecule, which led to the production of 2,6-dibromo-4-isopropyl
      phenol and three unidentified metabolites. Another metabolite of TBBPA
      characterized as a hexa-brominated compound with three aromatic rings was also
      found in the liver subcellular fractions. These results suggest that the
      biotransformation of BDE 15 and TBBPA in fish liver is mediated by cytochrome
      P450 (CYP450) enzymes, as revealed by the formation of hydroxylated metabolites
      and oxidative bond cleavage products. Moreover, further studies on the
      identification of specific CYP450 isozymes involved in the biotransformation
      revealed that CYP1A was the major enzyme responsible for the biotransformation of
      BDE 15 and TBBPA in fish liver subcellular fractions and CYP3A4 also played a
      major role in metabolism of TBBPA.

PMID- 22417764
TI  - Effects of carbon nanomaterials fullerene C60 and fullerol C60(OH)18-22 on gills
      of fish Cyprinus carpio (Cyprinidae) exposed to ultraviolet radiation.
AB  - In consequence of their growing use and demand, the inevitable environmental
      presence of nanomaterials (NMs) has raised concerns about their potential
      deleterious effects to aquatic environments. The carbon NM fullerene (C60), which
      forms colloidal aggregates in water, and its water-soluble derivative fullerol
      (C60(OH)18-22), which possesses antioxidant properties, are known to be photo
      excited by ultraviolet (UV) or visible light. To investigate their potential
      hazards to aquatic organisms upon exposure to UV sunlight, this study analyzed
      (a) the in vitro behavior of fullerene and fullerol against peroxyl radicals
      (ROO) under UV-A radiation and (b) the effects of these photo-excited NMs on
      oxidative stress parameters in functional gills extracted from the fish Cyprinus
      carpio (Cyprinidae). The variables measured were the total antioxidant capacity,
      lipid peroxidation (TBARS), the activities of the antioxidant enzymes glutathione
      reductase (GR) and glutamate cysteine ligase (GCL), and the levels of the non
      enzymatic antioxidant glutathione (GSH). The obtained results revealed the
      following: (1) both NMs behaved in vitro as antioxidants against ROO in the dark
      and as pro-oxidants in presence of UV-A, the latter effect being reversed by the
      addition of sodium azide, which is a singlet oxygen (1O2) quencher; (2) fullerene
      induced toxicity with or without UV-A incidence, with a significant (p<0.05)
      increase in lipid peroxidation (with greater damage under illumination), a
      decrease in GCL activity, and the depletion of GSH stocks (under illumination),
      all of which were attributed to 1O2 generation; and (3) fullerol also decreased
      GCL activity and GSH formation (p<0.05) but without lipid damage. The overall
      results show that fullerene can be toxic with or without light incidence, whereas
      UV radiation seems to play a key role in the environmental toxicity of carbon NMs
      through 1O2 formation.

PMID- 22417765
TI  - A time-course analysis of effects of the steroidogenesis inhibitor ketoconazole
      on components of the hypothalamic-pituitary-gonadal axis of fathead minnows.
AB  - The objective of this study was to evaluate temporal effects of the model
      steroidogenesis inhibitor ketoconazole (KTC) on aspects of reproductive endocrine
      function controlled by the hypothalamic-pituitary-gonadal (HPG) axis in the
      fathead minnow (Pimephales promelas). Ketoconazole inhibits the activity of two
      cytochrome P450s (CYPs) key to sex steroid production in vertebrates, CYP11a
      (cholesterol side chain cleavage) and CYP17 (c17alpha-hydroxylase/17, 20-lyase).
      Sexually mature fish were exposed to water-borne KTC (30 or 300 MUg/L) in a flow
      through system for up to 8d, following which animals were allowed to recover in
      clean water. Fish were sampled after 1, 4 and 8d of exposure, and after 1, 8 and
      16d of recovery. A shorter-term time-course experiment also was conducted in
      which females were sampled on seven occasions during a 12h KTC exposure.
      Ketoconazole consistently depressed ex vivo gonadal synthesis of testosterone (T)
      in both sexes, and 17beta-estradiol (E2) in females during both exposure and
      recovery phases of the time-course studies. Effects on ex vivo steroidogenesis in
      females occurred within as little as 1h of exposure. Plasma concentrations of T
      in males and E2 in females also were depressed by exposure to KTC, but these
      decreases did not persist to the same degree as observed for the ex vivo effects.
      In females, after decreases within 12h, plasma E2 concentrations were similar to
      (or greater than) controls at 24h of exposure, while in males, plasma T returned
      to levels comparable to controls within 1d of cessation of KTC exposure. The
      discrepancy between the ex vivo and in vivo data at later stages in the test is
      consistent with some type of compensatory response to KTC in fish. However, we
      were unable to ascertain the mechanistic basis for such a response. For example,
      although a number of genes related to steroid synthesis (e.g., cyp11a, cyp17)
      were up-regulated in the gonads of both males and females during the exposure and
      early recovery phases of the experiment, this did not seem to account for the
      resurgence in plasma steroid concentrations in KTC-exposed fish. Further studies
      focused on metabolism and clearance of steroids might lend insights as to the
      effects of KTC on plasma steroid concentrations. Overall, our results demonstrate
      the complex, temporally dynamic nature of the vertebrate HPG system in response
      to chemical stressors.

PMID- 22417766
TI  - Intersite variations of a battery of biomarkers at different levels of biological
      organisation in the estuarine endobenthic worm Nereis diversicolor (Polychaeta,
      Nereididae).
AB  - The ragworm Nereis diversicolor has been proposed as a sentinel species for the
      assessment of estuarine sediment quality. The aim of this study was to test the
      responsiveness of the worms using a battery of biomarkers in specimens from a
      moderately contaminated site (Loire estuary, Fr.) and a comparatively cleaner
      site (Bay of Bourgneuf, Fr.) as a reference site. Ragworms were collected on 7
      occasions from April 2008 to October 2009 for the determination of biochemical
      (GST, AChE, digestive enzymes), physiological (energy reserves (glycogen, lipids
      and proteins), relationship between length and weight), and behavioural (feeding
      and burrowing) biomarkers. The biomarker responses were tentatively interpreted
      in terms of the concept of cascading events potentially responsible for local
      depletion/extinction of populations submitted to chemical stress. Impairments of
      AChE and amylase activities, feeding rate, energy reserve concentrations
      (glycogen and lipids), and the relationship between length and weight showed up
      differences between the reference site and the Loire estuary despite the latter
      being far from the most contaminated estuary in France or internationally.
      However, no links could be established in the Loire estuary ragworms between
      effects at infra-individual and individual levels, nor with worm population
      density, even though a small oil spill had occurred in the Loire estuary only one
      month before the beginning of sampling.

PMID- 22417767
TI  - Identifying brain imaging correlates of clinical response to repetitive
      transcranial magnetic stimulation (rTMS) in major depression.
AB  - BACKGROUND: Partial response and non-response to treatments are common problems
      in major depression. The identification of biological markers of clinical
      response may be of special interest for some adjunctive treatments, such as
      repetitive transcranial magnetic stimulation (rTMS), as it may ultimately improve
      their cost-effectiveness. OBJECTIVE: To identify pre-treatment functional imaging
      correlates of clinical response to rTMS in major depression. METHODS: We
      evaluated 21 depressed patients. They were randomized to receive 15 sessions of
      active or sham rTMS on the left dorsolateral prefrontal cortex. Functional
      magnetic resonance imaging (fMRI) was used to assess pre-treatment regional brain
      activity evoked by a word generation task. These regional activations were
      correlated (voxel-wise) with the Hamilton Rating Scale for Depression (HAM-D)
      reduction between baseline and end of treatment. A group of 13 healthy controls
      was also assessed using the same fMRI protocol to obtain reference imaging
      measurements. RESULTS: At the end of treatment, the percentage of patients with a
      HAM-D reduction greater than 50% was larger in the active than in the sham rTMS
      group (70% vs. 27.3%). In the active rTMS group, larger HAM-D reductions were
      significantly correlated with smaller deactivations during pre-treatment fMRI
      assessment in the anterior cingulate, the left medial orbitofrontal and the right
      middle frontal cortices, in addition to larger activations in the left ventral
      caudal putamen. CONCLUSIONS: These results suggest that brain activity in regions
      arguably relevant for major depression may predict clinical response to rTMS.
      This approach may help in identifying the most suitable candidates to undergo
      rTMS treatment.

PMID- 22417768
TI  - Biomechanical mechanisms of orbital wall fractures - a transient finite element
      analysis.
AB  - As the biomechanical mechanisms of orbital wall fractures are still under
      research, three different fracture mechanisms were tested in a finite element
      based investigation. In contrast to earlier studies, a finer skeletal model and a
      transient dynamic simulation were used to test pure hydraulic, pure buckling and
      a mixed force transmission. Results showed that each set-up led to different
      orbital fracture patterns, which correlate well with clinical findings. Therefore
      the conclusion is that different mechanisms may act together explaining the
      variety of clinical fracture situations. Biomechanical testing has proven to be
      appropriate in answering questions regarding fracture mechanisms. 

PMID- 22417769
TI  - Oral findings associated with primary hyperoxaluria type I.
AB  - In the present paper we report the oral findings of a patient who was diagnosed
      with hyperoxaluria. Hyperoxalurias can basically be classified as primary and
      secondary, with the first being inborn errors of metabolism and the second a
      result of excessive oxalate intake. Primary hyperoxalurias form a rare group of
      metabolic diseases that are inherited in the autosomal recessive fashion. The
      affected genes code for specific hepatic enzymes that are involved in glyoxylate
      metabolism and their deficiency results in overproduction of oxalate. Two
      different types are described: Primary hyperoxaluria type I results from a
      deficiency of peroxisomal enzyme alanine-glyoxylate aminotransferase and the more
      rare type II from a deficiency of cytosolic enzyme D-glycerate dehydrogenase.
      Since oxalate is primarily excreted through the kidneys, abnormally high
      concentration of oxalate in the urine occurs. This can in turn result in
      recurrent kidney stones and parenchymal renal damage and end-stage renal disease
      (ESRD). Inability to further excrete oxalate through the kidneys leads to its
      deposition in various organs (oxalosis). Several oral findings have been
      described in patients with oxalosis, most important of whose are bone resorption
      in the jaws, external root resorption and rapidly progressive dental mobility, as
      well as dental pain associated with deposition of oxalate in the dentine and the
      pulp.

PMID- 22417770
TI  - Surgical outcome after using a modified technique of the pi-procedure for
      posterior sagittal suture closure.
AB  - Fusion of the sagittal suture is the most prevalent form of craniosynostosis. Due
      to the variety of deformities of scaphocephaly depending on the location of the
      fused sagittal suture, the surgical procedure has to be adjusted to the
      individual case. In this study, 38 patients with a predominantly posterior
      sagittal suture closure were treated with a modified technique of the pi
      procedure and the surgical outcome has been evaluated with respect to
      complications, morphological and aesthetic outcome. The improvement of the
      cephalic index in our series in the follow-up examination (mean 60.1 months)
      after surgery was significant (p<0.0001). According to the classification of
      Whitaker, 31 patients had a Class 1 outcome, with excellent surgical results.
      Aesthetic outcomes were excellent in 29, good in 5, and poor in 4 of cases, as
      judged by both the families and the craniofacial team. No severe complications
      have been observed. Posterior sagittal suture with marked occipital bulging can
      be successfully treated with this modified posterior procedure with a low
      complication rate, significant improvement of the cephalic index and a good
      aesthetic outcome. In all cases of sagittal synostosis, the operative procedure
      should be tailored to the nature and severity of the deformity.

PMID- 22417771
TI  - Squamous cell carcinoma arising in dentigerous cysts.
AB  - We present two cases of squamous cell carcinoma (SCC) arising in dentigerous
      cysts. Malignant transformation in dentigerous cysts is rare giving rise to
      diagnostic difficulties. We propose imaging at an early stage to reduce delays in
      diagnosis.

PMID- 22417772
TI  - Three-dimensional prospective evaluation of tooth-borne and bone-borne surgically
      assisted rapid maxillary expansion.
AB  - AIM: To three-dimensionally (3D) assess the long-term effects of tooth-borne and
      bone-borne surgically assisted rapid maxillary expansion (SARME). SUBJECTS AND
      METHODS: This prospective cohort study comprised 45 consecutive skeletally mature
      non-syndromic patients with transverse maxillary hypoplasia. In 28 patients, a
      tooth-borne distractor (Hyrax) was used for expansion, whereas in the remaining
      17 a bone-borne distractor (transpalatal distractor, TPD) was used. Cone beam
      computed tomography (CBCT) scans were performed before treatment (T0) and 22
      months later, after fixed appliance treatment (T1). 3D models were constructed
      from CBCT data and superimposed using voxel-based matching. Distance maps between
      the superimposed models were computed to evaluate the amount of skeletal changes.
      RESULTS: The distance maps of the superimposed models showed positive distances
      on the right and left posterior alveolar segments of the maxilla indicating
      lateral expansion. The anterior maxillary region showed negative distances or
      posterior displacement and remodelling of the anterior alveolar region. There was
      no statistically significant difference between TPD and Hyrax for the three
      alveolar segments (p values ranged 0.63-0.81). CONCLUSION: Bone-borne and tooth
      borne SARME were found to produce comparable results at the end of fixed
      appliance treatment regarding skeletal changes.

PMID- 22417774
TI  - Propolis alleviates 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced histological
      changes, oxidative stress and DNA damage in rat liver.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces hepatic damage. Propolis
      exhibits antioxidant properties and several studies suggest that supplementations
      with antioxidants can influence hepatotoxicity. Therefore, the aim of the current
      study was to explore the effectiveness of propolis in alleviating the toxicity of
      TCDD in the liver of rats. Animals were divided into six groups, namely, TCDD
      (0.75 and 8 ug/kg body weight (bw)), propolis (50 mg/kg bw), TCDD (0.75 and 8 ug)
      plus propolis (50 mg/kg bw), and control, respectively. Rats were
      intraperitoneally administered with their respective doses daily for 21 days. In
      rats that received a high dose of TCDD, the antioxidant enzymes were
      significantly decreased and the serious pathological findings were established.
      Also, the rate of hepatocyte micronucleus (HMN) was increased after treating with
      TCDD. The reactions of enzymes in control and low-dose group were weak. The
      frequencies of HMN and liver histology were similar to both the groups. The
      presence of propolis with TCDD alleviated its pathological effects in hepatic
      tissue. Propolis also prevented the suppression of antioxidant enzymes in the
      livers of animals exposed to TCDD and displayed a strong protective effect
      against HMN. It can be concluded that propolis has beneficial influences and was
      able to antagonize TCDD toxicity in the liver. 

PMID- 22417775
TI  - Tricks of the trade: How to avoid histological pitfalls in celiac disease.
AB  - Currently, the diagnosis of celiac disease (CD) is based upon the combination of
      raised serum anti-tissue transglutaminase or anti-endomysial antibodies and the
      presence of histological alterations of variable degree in the duodenal mucosa.
      Interpretation of duodenal biopsies is subjected to a number of variables, and
      the lack of standardization may cause diagnostic controversy or even
      misdiagnosis. The aim of this overview is to solicit a standardization of the
      procedures of biopsy taking, orientation, processing, staining and interpretation
      in order to avoid or minimize misinterpretation of duodenal biopsies. Based on a
      literature review and extensive personal experience, the appropriate methodology
      of duodenal biopsy taking, orientation, fixation, processing, staining and
      interpretation was thoroughly reviewed, and the most common and relevant errors
      and artifacts were identified. To maximize the diagnostic yield of duodenal
      biopsy in CD, multiple specimens are best taken from different sites of the
      duodenum during endoscopy, and careful visual inspection of the duodenal mucosa
      may help identify abnormalities related to villous atrophy. Biopsy handling and
      orientation are of utmost importance to avoid artifacts that may impair the
      pathologist's ability to detect pathology and normality. Immunostaining with anti
      CD3 monoclonal antibody should be carried out, and a simplified histological
      classification may help distinguish atrophic from non-atrophic stages of CD
      enteropathy. Meticulous attention to biopsy orientation, handling and processing 
      together with the knowledge of the most common histological artifacts - is
      necessary to avoid a wrong histological interpretation which, in turn, may lead
      to misdiagnosis in CD.

PMID- 22417773
TI  - Neurologic effects of exogenous saccharides: a review of controlled human,
      animal, and in vitro studies.
AB  - OBJECTIVES: Current research efforts are centered on delineating the novel health
      benefits of naturally derived saccharides, including growing interest in their
      abilities to influence neurologic health. We performed a comprehensive review of
      the literature to consolidate all  controlled studies assessing various roles of
      exogenous saccharide compounds and polysaccharide-rich extracts from plants,
      fungi, and other natural sources on brain function, with a significant focus on
      benefits derived from oral intake. METHODS: Studies were identified  by
      conducting electronic searches on PubMed and Google Scholar. Reference lists of
      articles were also reviewed for additional relevant studies. Only articles
      published in English were included in this review. RESULTS: Six randomized,
      double-blind, placebo-controlled clinical  studies were identified in which
      consumption of a blend of plant-derived polysaccharides showed positive effects
      on cognitive function and mood in healthy adults. A separate controlled clinical
      study observed improvements in well-being with ingestion of a yeast beta-glucan.
      Numerous animal  and in vitro studies have demonstrated the ability of individual
      saccharide compounds and polysaccharide-rich extracts to modify behavior, enhance
      synaptic plasticity, and provide neuroprotective effects. DISCUSSION: Although
      the mechanisms by which exogenous saccharides  can influence brain function are
      not well understood at this time, the literature suggests that certain naturally
      occurring compounds and polysaccharide-rich extracts show promise, when taken
      orally, in supporting neurologic health and function. Additional well-controlled
      clinical studies  on larger populations are necessary, however, before specific
      recommendations can be made.

PMID- 22417776
TI  - Effect of pregnancy on serum cytokines in SLE patients.
AB  - INTRODUCTION: The aim of this study was to evaluate an extensive panel of
      cytokines involved in immune regulation during pregnancy in patients with
      systemic lupus erythematosus (SLE) and in healthy women. METHODS: A total of 47
      consecutive successful pregnancies in 46 SLE patients and 56 pregnancies in 56
      matched healthy subjects, as controls, were prospectively studied. Serum
      interleukin (IL)-1-alpha, IL-1-beta, IL-2, IL-6, IL-8, IL-10, IL-12p70,
      interferon (INF)-gamma and tumor necrosis factor (TNF)-alpha were detected in
      sera obtained at the first and third trimester of pregnancy by a highly
      sensitive, multiplexed sandwich ELISA. RESULTS: Medians (pg/ml) of serum levels
      of most helper T (Th)1-type cytokines were significantly lower in the third
      trimester compared with those observed in the first trimester of pregnancy in
      healthy women: INF-gamma 2.0 vs 3.4, TNF-alpha 10.2 vs 11.5, IL-1-alpha 0.9 vs
      1.1, IL-1-beta 0.6 vs 1.0, IL-2 3.0 vs 3.5, and IL-12p70 4.9 vs 5.6 (P-values <
      0.02 for all). By contrast, only the IL-1-alpha serum levels were lower in the
      third trimester compared with the first trimester in SLE patients (P = 0.006).
      IFN-gamma/IL-6 and IFN-gamma/IL-10 ratios were higher in controls than in SLE (P
      = 0.002, and P = 0.001, respectively); moreover, they were significantly reduced
      in the third compared to the first trimester of pregnancy in healthy women, but
      not in SLE. CONCLUSIONS: In SLE patients, Th1/Th2 cytokine serum level ratio does
      not decrease during pregnancy progression as much as in healthy pregnant women.
      This could account for the observation of a low frequency of disease flares in
      the third trimester of gestation.

PMID- 22417777
TI  - Fragrance material review on p-anisyl acetate.
AB  - A toxicologic and dermatologic review of p-anisyl acetate when used as a
      fragrance ingredient is presented. p-Anisyl acetate is a member of the fragrance
      structural group aryl alkyl alcohol simple acid esters (AAASAE). The AAASAE
      fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a
      simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate,
      propionate, butyrate, isobutyrate and carbonate esters. This review contains a
      detailed summary of all available toxicology and dermatology papers that are
      related to this individual fragrance ingredient and is not intended as a stand
      alone document. Available data for p-anisyl acetate were evaluated, then
      summarized, and includes: physical properties, acute toxicity, skin irritation,
      mucous membrane (eye) irritation, skin sensitization, and genotoxicity data. A
      safety assessment of the entire AAASAE will be published simultaneously with this
      document. Please refer to Belsito et al. (2012) for an overall assessment of the
      safe use of this material and all AAASAE in fragrances.

PMID- 22417778
TI  - Safety and tolerance of Bacteroides xylanisolvens DSM 23964 in healthy adults.
AB  - We recently presented the strain Bacteroides xylanisolvens DSM 23964 to be safe
      for use in food. In order to confirm the tolerance of healthy humans to a regular
      oral intake of the strain B. xylanisolvens DSM 23964, we here report on the
      safety data of two successive human studies: a randomised and double-blind
      parallel group-controlled pilot study with 41 volunteers receiving a daily dose
      of a pasteurised fermented milk product containing up to 8.5*1011B. xylanisolvens
      DSM 23964 cells for 3 weeks, and a randomised and placebo-controlled double-blind
      major study with 140 volunteers receiving the same product but spray-dried and
      containing up to 1012 cells for 6 weeks. In both studies no persistent side
      effects of any kind were reported. The measured haematological parameters, and
      the serum concentrations of immunoglobulin and of inflammatory markers (IL-6,
      CRP, IFN-gamma) were unaffected by the supplementation in both studies. A small
      decrease in the phagocytic activity of granulocytes and a small increase of TNF
      alpha detected in the pilot study were both invalidated by the major study. This
      study further revealed that the supplementation induced no modification in
      natural killer cell activity and in liver enzyme values (gamma-glutamyl
      transferase, glutamate-oxalacetate transaminase, glutamate-pyruvate
      transaminase). Our results definitively demonstrate that the pasteurised B.
      xylanisolvens DSM 23964 strain is safe and well tolerated by healthy human
      individuals.

PMID- 22417779
TI  - Patient views of single number access to urgent care services.
AB  - BACKGROUND: In October 2009, NHS County Durham and Darlington introduced a single
      point of access telephone number for people requiring out-of-hours health care.
      We evaluated users' views and experiences of the service. METHODS: We used a
      validated questionnaire adapted for use in telephone interviews, with open-ended
      questions added to allow people to express their views. Interviews were carried
      out with 493 people who had used the urgent care line between April and July 2010
      of 1626 telephone calls made, a response rate of 30.3%. SPSS 17.0 was used to
      analyse the quantitative data and Framework analysis the qualitative data.
      RESULTS: We found that (i) regardless of age or gender people who used the call
      line were satisfied with the service they received, (ii) the call line advised
      most cases to go to an urgent care centre, (iii) people who received advice other
      than that expected were still satisfied with the service. Criticisms of the
      service related to confusion about accessing the service and which number callers
      should use. CONCLUSIONS: We found very high levels of satisfaction across all
      groups for a single point of access telephone number for urgent care. Clear
      information about the service, in particular that it will involve telephone
      triage and that access to a doctor or nurse is not immediate, may also resolve
      some instances of dissatisfaction. It appears that the service is effective in
      directing people to places where they can be dealt with appropriately.

PMID- 22417780
TI  - The modulation of Jahn-Teller coupling by elastic and binding strain
      perturbations-a novel view on an old phenomenon and examples from solid-state
      chemistry.
AB  - Cations in 6-coordination with orbitally degenerate E(g) ground states, such as
      Cu(2+) and low-spin Co(2+), play an important role in coordination chemistry-in
      particular, in modern complex biochemistry. The stereochemistry and the binding
      properties within the basic polyhedra are the subject of pronounced modifications
      due to vibronic coupling in such cases, but may be also significantly influenced
      by what is usually called an imposed strain. The latter effect makes allowance
      for the general observation that the host sites into which the Jahn-Teller
      unstable centers are substituted are seldom of O(h) symmetry and built from six
      equal ligands. Hence, the finally observed molecular and binding structure of the
      pseudo-octahedral complex is the result of the combined action of vibronic
      coupling and strain. The closer analysis of host-site strain effects demands to
      distinguish between elastic strain components, which modify the force constant of
      the vibronically active (here, epsilon(g)) vibration, and binding strain
      perturbations, which take account of possibly present ligands with different
      binding properties. A symmetry-met semiempirical strain model on such a basis is
      presented and a corresponding formulation within the vibronic coupling formalism
      is given, on the molecular level. Well-established model examples of Cu(2+) in
      octahedral fluoride coordination in various host solids, where a great variety of
      experimental results is available, are given. The derived parameters allow a
      detailed characterization of the structural and energy qualities of the Jahn
      Teller centers, and might help to steer these properties in cases where synthesis
      strategies are needed. The proposed strain concept is more complex than that of
      Ham [F. S. Ham, Electron Paramagnetic Resonance; Plenum Press: New York, 1972; F.
      S. Ham, Phys. Rev. 1965, A138, 1727]; the advantage is that it is directly tied
      to the structure and energy of the Jahn-Teller complex in focus, although more
      data (experimental and possibly computed) are needed in such a model.

PMID- 22417781
TI  - The role of horses in the transmission of leptospirosis in an urban tropical
      area.
AB  - The objective of this study was to demonstrate the presence of leptospires in
      equine urine, as evidence for a potential role of horses in transmission of this
      organism. Thoroughbred horses (aged 2-5 years, n = 276) from Rio de Janeiro,
      Brazil, were studied. After a severe storm, the premises of the animals remained
      flooded for 72 h. Blood samples for serology were collected on days 20 and 35
      (day of storm = day 0). On day 20, 132 (47.8%) horses were seroreactive (titre
      >=200) and, of these, 23 (31.0%) had increased antibody titres on day 35.
      Furthermore, 34 urine samples (for PCR and culture) were collected from
      seroreactive horses on day 35. Copenhageni was the most frequent serovar (88.8%
      of reactive titres). Although none of the urine samples were culture positive, 12
      (35.2%) were PCR positive. This is apparently the first report of evidence of
      leptospires in urban horses. Furthermore, we suggest that these animals can play
      a role in the transmission of leptospirosis in urban areas.

PMID- 22417782
TI  - Determination of chlorinated paraffins in sediments from the Firth of Clyde by
      gas chromatography with electron capture negative ionisation mass spectrometry
      and carbon skeleton analysis by gas chromatography with flame ionisation
      detection.
AB  - Short chain chlorinated paraffins (SCCPs) are a group of persistent organic
      pollutants (POPs) of increasing concern, but are to date not widely investigated
      in the environment, largely due to the challenges involved in their
      quantification. Here, SCCPs were quantified in marine sediments from the Firth of
      Clyde, Scotland, by gas chromatography with electron capture negative ionisation
      mass spectrometry (GC-ECNIMS) and through carbon skeleton analysis by gas
      chromatography with flame ionisation detection (GC-FID), and the analytical
      challenges encountered are discussed. Concentrations in the sediments ranged from
      0.4 to 69 MUg kg(-1) when determined by GC-ECNIMS, and from 5.6 to 379 MUg kg(-1)
      when determined by GC-FID. For 8 out of 11 samples, analysis by GC-FID gave
      higher results than analysis by GC-ECNIMS. Unexpected aspects of the analysis,
      such as the presence of high concentrations of longer chain chlorinated paraffins
      in the samples, are also presented.

PMID- 22417784
TI  - Detecting rotating magnetic fields using optically pumped atomic magnetometers
      for measuring ultra-low-field magnetic resonance signals.
AB  - In this paper, we describe the detection of rotating magnetic fields using
      optically pumped atomic magnetometers (OPAMs) for measuring magnetic resonance
      (MR) signals. From the results of rotating- and alternating-magnetic-field
      measurements, we found that to detect a rotating magnetic field with high
      sensitivity, the rotation direction of the magnetic field to be measured must
      select the bias-magnetic-field direction of OPAM. In addition, the OPAM
      sensitivity for rotating magnetic fields should be twice that for alternating
      magnetic fields. These results indicate that for measuring MR signals, magnetic
      fields caused by rotating magnetizations can be detected with the sensitivity of
      10 fT(rms)/Hz order at 1 kHz using OPAMs.

PMID- 22417783
TI  - Circadian clock genes and implications for intestinal nutrient uptake.
AB  - There has recently been increasing interest in the phenomenon of circadian
      rhythmicity. We have used circadian rhythms as a means to understanding the
      regulation of glucose absorption in the intestine. We and others have previously
      demonstrated rhythmicity in intestinal glucose uptake, mediated by rhythmicity in
      the expression of the sodium glucose cotransporter 1. Rhythmicity of clock gene
      expression was subsequently confirmed in the intestine, a phenomenon also
      demonstrated in other viscera. Clock genes have since been shown via a
      combination of in vitro and in vivo techniques to play a role in the
      transcriptional regulation of key absorptive proteins.

PMID- 22417785
TI  - Clinicopathologic correlations in multiple myeloma: a case series of 190 patients
      with kidney biopsies.
AB  - BACKGROUND: Renal involvement is common in multiple myeloma. In this study, we
      examined kidney biopsy findings in patients with multiple myeloma and correlated
      them with their clinical renal and hematologic characteristics. STUDY DESIGN:
      Case series. SETTING & PARTICIPANTS: 190 Mayo Clinic patients with multiple
      myeloma who underwent kidney biopsy between 1997-2011 were identified from our
      kidney biopsy database. Patients had an established diagnosis of multiple myeloma
      or multiple myeloma was diagnosed shortly after the results of kidney biopsy,
      which prompted bone marrow biopsy. PREDICTORS: Myeloma cast nephropathy (MCN), AL
      amyloidosis, and monoclonal immunoglobulin deposition disease (MIDD). OUTCOMES &
      MEASUREMENTS: Renal morphologic changes, clinical renal and hematologic
      characteristics at kidney biopsy, renal and patient outcomes. RESULTS:
      Paraprotein-associated lesions were seen in 73% of patients; non-paraprotein
      associated lesions, in 25%; and no pathology, in 2%. The most common paraprotein
      associated lesions were MCN (33%), MIDD (22%), and amyloidosis (21%). The most
      common non-paraprotein-associated lesions were acute tubular necrosis (9%),
      hypertensive arteriosclerosis (6%), and diabetic nephropathy (5%). Patients with
      MIDD were younger than those with MCN or amyloidosis. Urine paraprotein size and
      bone marrow plasma cell percentage were higher in MCN than amyloidosis or MIDD.
      Nephrotic syndrome was more common in amyloidosis than MIDD. Percentage of
      albuminuria was highest in amyloidosis and lowest in MCN. Median kidney survival
      from kidney biopsy was 20, 30, and 51 months for MCN, amyloidosis, and MIDD,
      respectively (P = 0.2). Median patient survival from multiple myeloma diagnosis
      was 44, 58, and 62 months for MCN, amyloidosis, and MIDD, respectively (P = 0.4).
      LIMITATIONS: Retrospective nature. CONCLUSIONS: The spectrum of renal lesions in
      multiple myeloma is more heterogeneous than previously reported. Clinical
      features favoring amyloidosis over MIDD include older age, absence of kidney
      failure, presence of nephrotic syndrome, absence of hematuria, and >50%
      albuminuria.

PMID- 22417786
TI  - Dialysis modality preference of patients with CKD and family caregivers: a
      discrete-choice study.
AB  - BACKGROUND: Dialysis modality preferences of patients with chronic kidney disease
      (CKD) and family caregivers are important, yet rarely quantified. STUDY DESIGN:
      Prospective, unlabeled, discrete-choice experiment with random-parameter logit
      analysis. SETTING & PARTICIPANTS: Adults with stages 3-5 CKD and caregivers
      educated about dialysis treatment options from 8 Australian renal clinics.
      PREDICTORS: Preferences for and trade-offs between the dialysis treatment
      attributes of life expectancy, number of hospital visits per week, ability to
      travel, hours per treatment, treatment time of day, subsidized transport service,
      and flexibility of treatment schedule. OUTCOMES & MEASUREMENTS: Results presented
      as ORs for preferring home-based or in-center dialysis to conservative care.
      RESULTS: 105 predialysis patients and 73 family caregivers completed the study.
      Median patient age was 63 years, and mean estimated glomerular filtration rate
      was 18.1 (range, 6-34) mL/min/1.73 m(2). Median caregiver age was 61 years. Home
      based dialysis (either peritoneal or home hemodialysis) was chosen by patients in
      65% of choice sets; in-center dialysis, in 35%; and conservative care, in 10%.
      For caregivers, this was 72%, 25%, and 3%, respectively. Both patients and
      caregivers preferred longer rather than shorter hours of dialysis (ORs of 2.02
      [95% CI, 1.51-2.70] and 2.67 [95% CI, 1.85-3.85] for patients and caregivers,
      respectively), but were less likely to choose nocturnal than daytime dialysis
      (ORs of 0.07 [95% CI, 0.01-0.75] and 0.03 [95% CI, 0.01-0.20]). Patients were
      willing to forgo 23 (95% CI, 19-27) months of life expectancy with home-based
      dialysis to decrease their travel restrictions. For caregivers, this was 17 (95%
      CI, 16-18) patient-months. LIMITATIONS: Data were limited to stated preferences
      rather than actual choice of dialysis modality. CONCLUSIONS: Our study suggests
      that it is rare for caregivers to prefer conservative nondialytic care for family
      members with CKD. Home-based dialysis modalities that enable patients and their
      family members to travel with minimal restriction would be strongly aligned with
      the preferences of both parties.

PMID- 22417787
TI  - FTY720 improves functional recovery after spinal cord injury by primarily
      nonimmunomodulatory mechanisms.
AB  - Spinal cord injury (SCI) is an incapacitating injury that can result in limited
      functional recovery. We have previously shown increases in the lysophospholipid
      mediator, sphingosine-1-phosphate (S1P), in the spinal cord after contusion
      injury. To apply S1P receptor modulation to the treatment of SCI, we examined the
      therapeutic effects of FTY720, an S1P receptor agonist, on locomotor recovery
      after SCI in mice. Oral administration of FTY720 shortly after contusion SCI
      significantly improved motor function recovery, as assessed by both Basso Mouse
      Scale scores and Rotarod Performance test results. FTY720 induced lymphopenia and
      reduced T-cell infiltration in the spinal cord after SCI but did not affect the
      early infiltration of neutrophils and the activation of microglia. In addition,
      plasma levels and mRNA expression of inflammatory cytokines in the spinal cord
      after SCI were not attenuated by FTY720. Vascular permeability and astrocyte
      accumulation were both decreased by FTY720 in the injured spinal cord. The
      therapeutic effects of FTY720 were not solely dependent on immune modulation, as
      confirmed by the demonstration that FTY720 also ameliorated motor function after
      SCI in mice with severe combined immunodeficiency. Finally, the S1P(1) receptor
      agonist, SEW2871, partly mimicked the therapeutic effect of FTY720. Our data
      highlight the importance of immune-independent functions of FTY720 in decreasing
      vascular permeability and astrogliosis in the injured spinal cord and promoting
      locomotor function recovery after SCI.

PMID- 22417788
TI  - Bronchodilator response in patients with normal baseline spirometry.
AB  - BACKGROUND: Spirometry before and after bronchodilator is performed to assess air
      flow-limitation reversibility. In patients with normal baseline spirometry the
      frequency of a positive bronchodilator response, as defined by American Thoracic
      Society/European Respiratory Society criteria,  has not been described. METHODS:
      We retrospectively analyzed adult patients tested in 2 academic pulmonary
      function testing laboratories over a 7-year period, with specific attention to
      patients who underwent bronchodilator testing after a normal baseline spirometry
      (FEV(1), FVC,  and FEV(1)/FVC within normal limits). The frequency of a positive
      response to bronchodilator, defined as a 12% and 200 mL increase in either FEV(1)
      or FVC, was calculated and associated with demographic factors. RESULTS: Of the
      1,394 patients with normal spirometry who were  administered bronchodilator, 43
      (3.1%) had a positive response. The percent of patients responding to
      bronchodilator were grouped according to pre-bronchodilator FEV(1): > lower limit
      of normal to 90% of predicted = 6.9%, 90-100% of predicted = 1.9%, and > 100% of
      predicted  = 0%. An FEV(1)/FVC in the lowest 2 quartiles was associated with a
      higher frequency of bronchodilator response. Older patients were more likely to
      respond to bronchodilator, but no other demographic factors were associated with
      a positive bronchodilator response. CONCLUSIONS: In  our study population the
      frequency of a positive bronchodilator response in patients with normal baseline
      spirometry is 3.1%. None of the patients with a pre-bronchodilator FEV(1) > 100%
      of predicted and only 1.9% of patients with an FEV(1) between 90% and 100% of
      predicted  responded. Bronchodilator testing can be omitted in patients with
      normal spirometry and an FEV(1) above 90% of predicted, as they have a low
      probability of a positive response.

PMID- 22417789
TI  - Selective contribution of regional adiposity, skeletal muscle, and adipokines to
      glucose disposal in older adults.
AB  - OBJECTIVES: To study the relationships between muscle mass, regional adiposity,
      and adipokines and glucose disposal in an older population. DESIGN: Cross
      sectional analysis. SETTING: Community-dwelling volunteers from the Baltimore
      Longitudinal Study of Aging. PARTICIPANTS: Two hundred eighty men and 259 women
      with a mean age of 71.1 +/- 0.4 (range 55-96) and complete data on fasting plasma
      adiponectin and leptin, oral glucose tolerance test (OGTT) (plasma glucose
      available at 0, 20, 40, 60, 80, 100, and 120 minutes), thigh computed tomography
      (CT), physical activity levels, and anthropometric measures. MEASUREMENTS:
      Participants were classified into eight groups according to the presence of
      global adiposity (body mass index > 27 kg/m(2)), central adiposity (waist
      circumference > 88 cm for women and > 102 cm for men), and low muscle mass (CT
      thigh, lowest sex-specific tertile (93.8 cm(2) in women and 110.7 cm(2) in men)
      of adjusted thigh muscle area). Linear regression models were used to estimate
      the contribution of these eight groups to early glucose area under the curve
      (AUC) (t = 0-40 minutes), late glucose AUC (t = 60-120 minutes), and total
      glucose AUC (t = 0-120 minutes) from the OGTT. RESULTS: Regardless of muscle
      mass, individuals with a combination of central and global adiposity were more
      likely to have delayed glucose disposal rates (P < .05). A strong negative
      association was also found between circulating adiponectin levels and glucose
      disposal rates (early AUC, beta = -0.14; late AUC, beta = -0.20; and total AUC,
      beta = -0.20; P < .05 for all three AUCs) after adjusting for regional adiposity,
      muscle mass, circulating leptin levels, physical activity, age, and sex.
      CONCLUSION: Older individuals with global and central adiposity may be at risk of
      glucose intolerance unrelated to low muscle mass.

PMID- 22417790
TI  - Parasitoids as vectors of facultative bacterial endosymbionts in aphids.
AB  - Heritable bacterial endosymbionts play an important role in aphid ecology.
      Sequence-based evidence suggests that facultative symbionts such as Hamiltonella
      defensa or Regiella insecticola also undergo horizontal transmission. Other than
      through male-to-female transfer during the sexual generation in autumn, the
      routes by which this occurs remain largely unknown. Here, we tested if
      parasitoids or ectoparasitic mites can act as vectors for horizontal transfer of
      facultative symbionts. Using symbiont-specific primers for diagnostic PCR, we
      demonstrate for the first time, to our knowledge, that parasitoids can indeed
      transfer H. defensa and R. insecticola by sequentially stabbing infected and
      uninfected individuals of their host, Aphis fabae, establishing new, heritable
      infections. Thus, a natural route of horizontal symbiont transmission is also
      available during the many clonal generations of the aphid life cycle. No
      transmissions by ectoparasitic mites were observed, nor did parasitoids that
      emerged from symbiont-infected aphids transfer any symbionts in our experiments.

PMID- 22417791
TI  - Chicks, like children, spontaneously reorient by three-dimensional environmental
      geometry, not by image matching.
AB  - Spatial reorientation by layout geometry occurs in numerous species, but its
      underlying mechanisms are debated. While some argue that navigating animals'
      sense of place is based on geometric computations over three-dimensional
      representations, others claim it depends on panoramic image-matching processes.
      Because children reorient by subtle three-dimensional perturbations of the
      terrain and not by salient two-dimensional brightness contours on surfaces or
      freestanding columns, children's sense of place cannot be explained by image
      matching. To test image-matching theories in a different species, the present
      experiment investigates the reorientation performance of domestic chicks (Gallus
      gallus) in environments similar to those used with children. Chicks, like
      children, spontaneously reoriented by geometric relationships of subtle three
      dimensional terrains, and not by salient two-dimensional brightness contours on
      surfaces or columns. These findings add to the evidence for homologous navigation
      systems in humans and other vertebrates, and they cast doubt on image-matching
      theories of reorientation in these species.

PMID- 22417792
TI  - Leading edge vortex in a slow-flying passerine.
AB  - Most hovering animals, such as insects and hummingbirds, enhance lift by
      producing leading edge vortices (LEVs) and by using both the downstroke and
      upstroke for lift production. By contrast, most hovering passerine birds
      primarily use the downstroke to generate lift. To compensate for the nearly
      inactive upstroke, weight support during the downstroke needs to be relatively
      higher in passerines when compared with, e.g. hummingbirds. Here we show, by
      capturing the airflow around the wing of a freely flying pied flycatcher, that
      passerines may use LEVs during the downstroke to increase lift. The LEV
      contributes up to 49 per cent to weight support, which is three times higher than
      in hummingbirds, suggesting that avian hoverers compensate for the nearly
      inactive upstroke by generating stronger LEVs. Contrary to other animals, the LEV
      strength in the flycatcher is lowest near the wing tip, instead of highest. This
      is correlated with a spanwise reduction of the wing's angle-of-attack, partly
      owing to upward bending of primary feathers. We suggest that this helps to delay
      bursting and shedding of the particularly strong LEV in passerines.

PMID- 22417793
TI  - Cryptic asymmetry: unreliable signals mask asymmetric performance of crayfish
      weapons.
AB  - Animals commonly use their limbs as signals and weapons during territorial
      aggression. Asymmetries of limb performance that do not relate to asymmetries of
      limb size (cryptic asymmetry) could substantially affect disputes, but this
      phenomenon has not been considered beyond primates. We investigated cryptic
      asymmetry in male crayfish (Cherax dispar), which commonly use unreliable signals
      of strength during aggression. Although the strength of a chela can vary by an
      order of magnitude for a given size, we found repeatable asymmetries of strength
      that were only weakly related to asymmetries of size. Size-adjusted strength of
      chelae and the asymmetry of strength between chelae were highly repeatable
      between environmental conditions, suggesting that asymmetries of strength stemmed
      from variation in capacity rather than motivation. Cryptic asymmetry adds another
      dimension of uncertainty during conflict between animals, which could influence
      the evolution of unreliable signals and morphological asymmetry.

PMID- 22417794
TI  - The long and the short of avian W chromosomes: no evidence for gradual W
      shortening.
AB  - The well-established view of the evolution of sex chromosome dimorphism is of a
      gradual genetic and morphological degeneration of the hemizygous chromosome. Yet,
      no large-scale comparative analysis exists to support this view. Here, we
      analysed karyotypes of 200 bird species to test whether the supposed directional
      changes occur in bird sex chromosomes. We found no support for the view that W
      chromosomes gradually become smaller over evolutionary time. On the contrary, the
      length of the W chromosome can fluctuate over short time scales, probably
      involving both shortening and elongation of non-coding regions. Recent
      discoveries of near-identical palindromes and neo-sex chromosomes in birds may
      also contribute to the observed variation. Further studies are now needed to
      investigate how chromosome morphology relates to its gene content, and whether
      the changes in size were driven by selection.

PMID- 22417795
TI  - Prevalence of hip osteoarthritis in chiropractic practice in Denmark: a
      descriptive cross-sectional and prospective study.
AB  - OBJECTIVE: The purposes of this study were to measure the prevalence of clinical
      and radiographic hip osteoarthritis (OA) and first-time diagnosis of hip OA in
      consecutive patients presenting to chiropractic practices in Denmark and to
      report the components of the initial treatment rendered by the chiropractic
      practitioner. METHODS: A total of 2000 patient records and 1000 radiographs were
      reviewed retrospectively in 20 chiropractic clinics throughout Denmark.
      Information obtained included patients' primary complaint, physical examination
      and radiographic findings of hip OA, and treatment. Subsequently, the 20 clinics
      participated in a prospective survey where they collected equivalent information
      over a 2-week period. RESULTS: Retrospective review of records revealed that 1.4%
      of patients in Danish chiropractic practice had signs of clinical hip OA. Of
      these, 59% demonstrated radiographic signs of hip OA. Prospective data collection
      revealed that 3.4% of new patients had signs of clinical hip OA. Fifty-four
      percent of these demonstrated radiographic signs of hip OA, and of these 70% were
      diagnosed as having OA of the hip for the first time. Initial treatment involved
      manual treatment and advice on over-the-counter pain medication and/or
      supplements. Of all 1000 retrospectively reviewed radiographs in patients 40
      years or older, 19.2% demonstrated radiographic signs of hip OA. CONCLUSION:
      Osteoarthritis of the hip is diagnosed and managed in primary care chiropractic
      practice in Denmark; however, it is likely underdiagnosed. In those newly
      presenting to chiropractic practitioners, first-time diagnosis with clinical and
      radiographic signs of hip OA appears to be common.

PMID- 22417796
TI  - Development and preliminary validation of a tool to measure nurses' support for
      facilitating the learning of others.
AB  - BACKGROUND: Nurses guide and support learning of students and new graduates in
      the workplace. A plethora of literature exists about learners needs in the
      workplace however nursing leadership teams also need to support experienced
      nurses who facilitate others' learning. AIM: This study sought to develop a tool
      for Registered Nurses' to report on the support they receive when they facilitate
      the learning of others. SCALE DEVELOPMENT: An extensive literature review
      identified 28 papers about support RNs need to facilitate learning. Five re
      occuring themes pertaining to workload, communication, acknowledgement, teamwork
      and preparation for role emerged from analysis of these papers. These were
      verified independently through focus groups. A 30-item instrument was generated
      based on the themes; further RN focus groups were conducted to ensure clarity of
      items. TESTING OF INSTRUMENT: Data were collected from RNs working in medical and
      surgical areas across three acute care hospitals (ranging from 300 to 750 beds).
      A total of 372 registered nurses responded. Principle component analysis
      identified 5 distinct sub scales represented by 17 items with good reliability:
      workload 0.953; communication 0.847; acknowledgement 0.858; teamwork 0.852;
      preparation 0.942. CONCLUSION: This newly developed tool measures Registered
      Nurses perceptions of support they receive to fulfil their role in supporting the
      learning of others. The data generated from use of this tool can inform nursing
      leadership about the effectiveness of existing infrastructure and resources to
      support RNs.

PMID- 22417797
TI  - Isolation and purification of an axenic diazotrophic drought-tolerant
      cyanobacterium, Nostoc commune, from natural cyanobacterial crusts and its
      utilization for field research on soils polluted with radioisotopes.
AB  - Nitrogen fixation and drought tolerance confer the ability to grow on dry land,
      and some terrestrial cyanobacteria exhibit these properties. These cyanobacteria
      were isolated in an axenic form from Nostoc commune clusters and other sources by
      modifying the method used to isolate the nitrogen-fixing and drought-tolerant
      cyanobacterium Nostoc sp. HK-01. Of these cyanobacteria, N. commune, which is
      difficult to isolate and purify, uses polysaccharides to maintain water, nitrogen
      fertilizers for nitrogen fixation, and can live in extreme environments because
      of desiccation tolerance. In this study, we examined the use of N. commune as
      biosoil for space agriculture and possible absorption of radioisotopes ((134)Cs,
      (137)Cs). This article is part of a Special Issue entitled: Photosynthesis
      Research for Sustainability: from Natural to Artificial.

PMID- 22417798
TI  - Photosynthetic characteristics and enzymatic antioxidant capacity of leaves from
      wheat cultivars exposed to drought.
AB  - Two durum (Triticum durum L.), Barakatli-95 and Garagylchyg-2; and two bread
      (Triticum aestivum L.) wheat cultivars, Azamatli-95 and Giymatli-2/17 with
      different sensitivities to drought were grown in the field on a wide area under
      normal irrigation and severe water deficit. Drought caused a more pronounced
      inhibition in photosynthetic parameters in the more sensitive cvs Garagylchyg-2
      and Giymatli-2/17 compared with the tolerant cvs Barakatli-95 and Azamatli-95.
      Upon dehydration, a decline in total chlorophyll and relative water content was
      evident in all cultivars, especially in later periods of ontogenesis. Potential
      quantum yield of PS II (F(v)/F(m) ratio) in cv Azamatli-95 was maximal during
      stalk emergency stage at the beginning of drought. This parameter increased in cv
      Garagylchyg-2, while in tolerant cultivar Barakatli-95 significant changes were
      not observed. Contrary to other wheat genotypes in Giymatli-2/17 drought caused a
      decrease in PS II quantum yield. Drought-tolerant cultivars showed a significant
      increase in CAT activity as compared to control plants. In durum wheat cultivars
      maximal activity of CAT was observed at the milk ripeness and in bread wheat
      cultivars at the end of flowering. APX activity also increased in drought-treated
      leaves: in tolerant wheat genotypes maximal activity occurred at the end of
      flowering, in sensitive ones at the end of ear formation. GR activity increased
      in the tolerant cultivars under drought stress at all stages of ontogenesis. SOD
      activity significantly decreased in sensitive cultivars and remained at the
      control level or increased in resistant ones. This article is part of a Special
      Issue entitled: Photosynthesis Research for Sustainability: from Natural to
      Artificial.

PMID- 22417799
TI  - Identifying patients who are unsuitable for accelerated partial breast
      irradiation using three-dimensional external beam conformal techniques.
AB  - PURPOSE: Several recent studies reported that severe late toxicities including
      soft-tissue fibrosis and fat necrosis are present in patients treated with
      accelerated partial breast irradiation (APBI) and that these toxicities are
      associated with the large volume of tissue targeted by high-dose irradiation. The
      present study was performed to clarify which patients are unsuitable for APBI to
      avoid late severe toxicities. METHODS AND MATERIALS: Study subjects comprised 50
      consecutive patients with Stage 0-II unilateral breast cancer who underwent
      breast-conserving surgery, and in whom five or six surgical clips were placed
      during surgery. All patients were subsequently replanned using three-dimensional
      conformal radiotherapy (3D-CRT) APBI techniques according to the National
      Surgical Adjuvant Breast and Bowel Project (NSABP) B-39 and Radiation Therapy
      Oncology Group (RTOG) 0413 protocol. The beam arrangements included mainly
      noncoplanar four- or five-field beams using 6-MV photons alone. RESULTS: Dose
      volume histogram (DVH) constraints for normal tissues according to the NSABP/RTOG
      protocol were satisfied in 39 patients (78%). Multivariate analysis revealed that
      only long craniocaudal clip distance (CCD) was correlated with nonoptimal DVH
      constraints (p = 0.02), but that pathological T stage, anteroposterior clip
      distance (APD), site of ipsilateral breast (IB) (right/left), location of the
      tumor (medial/lateral), and IB reference volume were not. DVH constraints were
      satisfied in 20% of patients with a long CCD (>=5.5 cm) and 92% of those with a
      short CCD (p < 0.0001). Median IB reference volume receiving >=50% of the
      prescribed dose (IB-V(50)) of all patients was 49.0% (range, 31.4-68.6).
      Multivariate analysis revealed that only a long CCD was correlated with large IB
      V(50) (p < 0.0001), but other factors were not. CONCLUSION: Patients with long
      CCDs (>=5.5 cm) might be unsuitable for 3D-CRT APBI because of nonoptimal DVH
      constraints and large IB-V(50).

PMID- 22417800
TI  - Residual 18F-FDG-PET uptake 12 weeks after stereotactic ablative radiotherapy for
      stage I non-small-cell lung cancer predicts local control.
AB  - PURPOSE: To investigate the prognostic value of [(18)F]fluorodeoxyglucose
      positron emission tomography (FDG-PET) uptake at 12 weeks after stereotactic
      ablative radiotherapy (SABR) for stage I non-small-cell lung cancer (NSCLC).
      METHODS AND MATERIALS: From November 2006 to February 2010, 132 medically
      inoperable patients with proven Stage I NSCLC or FDG-PET-positive primary lung
      tumors were analyzed retrospectively. SABR consisted of 60 Gy delivered in 3 to 8
      fractions. Maximum standardized uptake value (SUV(max)) of the treated lesion was
      assessed 12 weeks after SABR, using FDG-PET. Patients were subsequently followed
      at regular intervals using computed tomography (CT) scans. Association between
      post-SABR SUV(max) and local control (LC), mediastinal failure, distant failure,
      overall survival (OS), and disease-specific survival (DSS) was examined. RESULTS:
      Median follow-up time was 17 months (range, 3-40 months). Median lesion size was
      25 mm (range, 9-70 mm). There were 6 local failures: 15 mediastinal failures, 15
      distant failures, 13 disease-related deaths, and 16 deaths from intercurrent
      diseases. Glucose corrected post-SABR median SUV(max) was 3.0 (range, 0.55
      14.50). Using SUV(max) 5.0 as a cutoff, the 2-year LC was 80% versus 97.7% for
      high versus low SUV(max), yielding an adjusted subhazard ratio (SHR) for high
      post-SABR SUV(max) of 7.3 (95% confidence interval [CI], 1.4-38.5; p = 0.019).
      Two-year DSS rates were 74% versus 91%, respectively, for high and low SUV(max)
      values (SHR, 2.2; 95% CI, 0.8-6.3; p = 0.113). Two-year OS was 62% versus 81%
      (hazard ratio [HR], 1.6; 95% CI, 0.7-3.7; p = 0.268). CONCLUSIONS: Residual FDG
      uptake (SUV(max) >=5.0) 12 weeks after SABR signifies increased risk of local
      failure. A single FDG-PET scan at 12 weeks could be used to tailor further follow
      up according to the risk of failure, especially in patients potentially eligible
      for salvage surgery.

PMID- 22417801
TI  - Do carbamazepine, gabapentin, or other anticonvulsants exert sufficient
      radioprotective effects to alter responses from trigeminal neuralgia
      radiosurgery?
AB  - PURPOSE: Laboratory studies have documented radioprotective effects with
      carbamazepine. We sought to determine whether carbamazepine or other
      anticonvulsant/neuroleptic drugs would show significant radioprotective effects
      in patients undergoing high-dose small-volume radiosurgery for trigeminal
      neuralgia. METHODS AND MATERIALS: We conducted a retrospective review of 200
      patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden)
      stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May
      2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm
      diameter collimators, with no previous microvascular decompression, and follow-up
      >=6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery,
      28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only
      gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other
      anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking
      other anticonvulsants or combinations. RESULTS: Pain improvement developed post
      radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief
      developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy
      developed in 27 of 200 patients (13.5%). We could not significantly correlate
      pain improvement or initial complete pain relief with use of carbamazepine,
      gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in
      univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias
      correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of
      28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical
      pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with
      lower risks of developing post-radiosurgery trigeminal neuropathy. New post
      radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and
      13% (23 of 187) of patients on gabapentin alone, with age <=70 years, and Type 1
      typical trigeminal neuralgia pain compared with 25% (7 of 28), 20% (23 of 114),
      and 33% (4 of 12) of patients taking no anticonvulsants, age >70 years, and
      partly atypical Type 2 trigeminal neuralgia, respectively. CONCLUSIONS: The use
      of carbamazepine or gabapentin at the time of radiosurgery does not decrease the
      rates of obtaining partial or complete pain relief after radiosurgery, but
      gabapentin may reduce the risks of developing post-radiosurgery trigeminal
      neuropathy.

PMID- 22417802
TI  - Celecoxib enhances the radiosensitizing effect of 7-hydroxystaurosporine (UCN-01)
      in human lung cancer cell lines.
AB  - PURPOSE: 7-Hydroxystaurosporine (UCN-01), a Chk1-specific inhibitor, showed
      promising in vitro and in vivo chemo- or radiosensitizing activity. However,
      there have been concerns about its limited therapeutic efficacy and risk of side
      effects. A method of enhancing the treatment efficacy of UCN-01 while not
      increasing its side effects on normal tissue may therefore be required to apply
      this drug in clinical settings. Celecoxib is a cyclooxygenase-2 (COX-2)-specific
      inhibitor that downregulates ataxia telangiectasia and rad3-related (ATR)
      protein, an upstream kinase of Chk1. In this study, we investigated whether the
      addition of celecoxib can potentiate the radiosensitizing effect of UCN-01.
      METHODS AND MATERIALS: The cooperative radiosensitizing effects and the
      underlying molecular mechanisms of UCN-01 plus celecoxib were determined by
      clonogenic assay, tumor growth delay assay, flow cytometry, and Western blotting.
      Synergism of the three agents combined (UCN-01 plus celecoxib plus radiation)
      were evaluated using median drug effect analysis and drug-independent action
      model analysis. RESULTS: The combination of UCN-01 and celecoxib could induce
      synergistic cytotoxicity and radiosensitizing effects in in vitro and in vivo
      systems. The combination of both drugs also cooperatively inhibited IR-induced
      G(2)/M arrest, and increased the G(2) to mitotic transition. CONCLUSIONS:
      Combined treatment with UCN-01 and celecoxib can exert synergistically enhanced
      radiosensitizing effects via cooperative inhibition of the ionizing radiation
      activated G(2) checkpoint. We propose that this combination strategy may be
      useful in clinical applications of UCN-01 for radiotherapy of cancer patients.

PMID- 22417803
TI  - Do we need daily image-guided radiotherapy by megavoltage computed tomography in
      head and neck helical tomotherapy? The actual delivered dose to the spinal cord.
AB  - PURPOSE: To quantify the actual delivered dose to the cervical spinal cord with
      different image-guided radiotherapy (IGRT) approaches during head and neck (HN)
      cancer helical tomotherapy. METHODS AND MATERIALS: Twenty HN patients (HNpts)
      treated with bilateral nodal irradiation were analyzed. Daily megavoltage
      computed tomography MVCT) scans were performed for setup purposes. The maximum
      dose on the planning CT scan (plan-Dmax) and the magnitude and localization of
      the actual delivered Dmax (a-Dmax) were analyzed for four scenarios: daily image
      guided radiotherapy (dIGRT), twice weekly IGRT (2*WkIGRT), once weekly IGRT
      (1*WkIGRT), and no IGRT at all (non-IGRT). The spinal cord was recontoured on 236
      MVCTs for each scenario (total, 944 fractions), and the delivered dose was
      recalculated for each fraction (fx) separately. RESULTS: Fifty-one percent of the
      analyzed fx for dIGRT, 56% of the analyzed fx for the 2*WkIGRT, 62% of the
      analyzed fx for the 1*WkIGRT, and 63% of the analyzed fx for the non-IGRT
      scenarios received a higher a-Dmax than the plan-Dmax. The median increase of
      dose in these fx was 3.3% more for dIGRT, 5.8% more for 2*WkIGRT, 10.0% more for
      1*WkIGRT, and 9.5% more for non-IGRT than the plan-Dmax. The median spinal cord
      volumes receiving a higher dose than the plan-Dmax were 0.02 cm3 for dIGRT, 0.11
      cm3 for 2*WkIGRT, 0.31 cm3 for 1*WkIGRT, and 0.22 cm3 for non-IGRT. Differences
      between the dIGRT and all other scenarios were statistically significant (p <
      0.05). CONCLUSIONS: Compared to the Dmax of the initial plan, daily IGRT had the
      smallest increase in dose. Furthermore, daily IGRT had the lowest proportion of
      fractions and the smallest volumes affected by a dose that was higher than the
      planned dose. For patients treated with doses close to the tolerance dose of the
      spinal cord, we recommend daily IGRT. For all other cases, twice weekly IGRT is
      sufficient.

PMID- 22417804
TI  - Long-term outcome in patients with ductal carcinoma in situ treated with breast
      conserving therapy: implications for optimal follow-up strategies.
AB  - PURPOSE: To determine 20-year rates of local control and outcome-associated
      factors for ductal carcinoma in situ (DCIS) after breast-conserving therapy
      (BCT). METHODS AND MATERIALS: All DCIS cases receiving BCT between 1980 and 1993
      were reviewed. Patient demographics and pathologic factors were analyzed for
      effect on outcomes, including ipsilateral breast tumor recurrence (IBTR) and
      survival. RESULTS: One hundred forty-five cases were evaluated; the median follow
      up time was 19.3 years. IBTR developed in 25 patients, for 5-, 10-, 15-, and 20
      year actuarial rates of 9.9%, 12.2%, 13.7%, and 17.5%, respectively. One third of
      IBTRs were elsewhere failures, and 68% of IBTRs occurred <10 years after
      diagnosis. Young age and cancerization of lobules predicted for IBTR at <10
      years, and increased slide involvement and atypical ductal hyperplasia were
      associated with IBTR at later time points. CONCLUSIONS: Patients with DCIS
      treated with BCT have excellent long-term rates of local control. Predictors of
      IBTR vary over time, and the risk of recurrence seems highest within 10 to 12
      years after diagnosis.

PMID- 22417805
TI  - Garcinol, a histone acetyltransferase inhibitor, radiosensitizes cancer cells by
      inhibiting non-homologous end joining.
AB  - PURPOSE: Non-homologous end joining (NHEJ), a major pathway used to repair DNA
      double-strand breaks (DSBs) generated by ionizing radiation (IR), requires
      chromatin remodeling at DSB sites through the acetylation of histones by histone
      acetyltransferases (HATs). However, the effect of compounds with HAT inhibitory
      activities on the DNA damage response (DDR), including the NHEJ and cell cycle
      checkpoint, as well as on the radiosensitivity of cancer cells, remains largely
      unclear. Here, we investigated whether garcinol, a HAT inhibitor found in the
      rinds of Garcinia indica fruit (called mangosteens), has effects on DDR, and
      whether it can be used for radiosensitization. METHODS AND MATERIALS: The
      following assays were used to examine the effect of garcinol on the inhibition of
      DSB repair, including the following: a conventional neutral comet assay; a cell
      based assay recently developed by us, in which NHEJ repair of DSBs on chromosomal
      DNA was evaluated; the micrococcal nuclease sensitivity assay; and immunoblotting
      for autophosphorylation of DNA-dependent protein kinase catalytic subunit (DNA
      PKcs). We assessed the effect of garcinol on the cell cycle checkpoint after IR
      treatment by analyzing the phosphorylation levels of checkpoint kinases CHK1 and
      CHK2 and histone H3, and by cell cycle profile analysis using flow cytometry. The
      radiosensitizing effect of garcinol was assessed by a clonogenic survival assay,
      whereas its effects on apoptosis and senescence were examined by annexin V and
      senescence-associated beta-galactosidase (SA-beta-Gal) staining, respectively.
      RESULTS: We found that garcinol inhibits DSB repair, including NHEJ, without
      affecting cell cycle checkpoint. Garcinol radiosensitized A549 lung and HeLa
      cervical carcinoma cells with dose enhancement ratios (at 10% surviving fraction)
      of 1.6 and 1.5, respectively. Cellular senescence induced by IR was enhanced by
      garcinol. CONCLUSION: These results suggest that garcinol is a radiosensitizer
      that inhibits NHEJ and facilitates senescence without impairing activation of the
      cell cycle checkpoint.

PMID- 22417806
TI  - Value of PET/CT and MR lymphography in treatment of prostate cancer patients with
      lymph node metastases.
AB  - PURPOSE: To determine the clinical value of two novel molecular imaging
      techniques: (11)C-choline positron emission tomography (PET)/computed tomography
      (CT) and ferumoxtran-10 enhanced magnetic resonance imaging (magnetic resonance
      lymphography [MRL]) for lymph node (LN) treatment in prostate cancer (PCa)
      patients. Therefore, we evaluated the ability of PET/CT and MRL to assess the
      number, size, and location of LN metastases in patients with primary or recurrent
      PCa. METHODS AND MATERIALS: A total of 29 patients underwent MRL and PET/CT for
      LN evaluation. The MRL and PET/CT data were analyzed independently. The number,
      size, and location of the LN metastases were determined. The location was
      described as within or outside the standard clinical target volume for elective
      pelvic irradiation as defined by the Radiation Therapy Oncology Group.
      Subsequently, the results from MRL and PET/CT were compared. RESULTS: Of the 738
      LNs visible on MRL, 151 were positive in 23 of 29 patients. Of the 132 LNs
      visible on PET/CT, 34 were positive in 13 of 29 patients. MRL detected
      significantly more positive LNs (p < 0.001) in more patients than PET/CT (p =
      0.002). The mean diameter of the detected suspicious LNs on MRL was significantly
      smaller than those detected by PET/CT, 4.9 mm and 8.4 mm, respectively (p <
      0.0001). In 14 (61%) of 23 patients, suspicious LNs were found outside the
      clinical target volume with MRL and in 4 (31%) of 13 patients with PET/CT.
      CONCLUSION: In patients with PCa, both molecular imaging techniques, MRL and
      (11)C-choline PET/CT, can detect LNs suspicious for metastasis, irrespective of
      the existing size and shape criteria for CT and conventional magnetic resonance
      imaging. On MRL and PET/CT, 61% and 31% of the suspicious LNs were located
      outside the conventional clinical target volume. Therefore, these techniques
      could help to individualize treatment selection and enable image-guided
      radiotherapy for patients with PCa LN metastases.

PMID- 22417807
TI  - A mathematical study to select fractionation regimen based on physical dose
      distribution and the linear-quadratic model.
AB  - PURPOSE: Hypofractionated irradiation is often used in precise radiotherapy
      instead of conventional multifractionated irradiation. We propose a novel
      mathematical method for selecting a hypofractionated or multifractionated
      irradiation regimen based on physical dose distribution adding to biologic
      consideration. METHODS AND MATERIALS: The linear-quadratic model was used for the
      radiation effects on tumor and normal tissues, especially organs at risk (OARs).
      On the basis of the assumption that the OAR receives a fraction of the dose
      intended for the tumor, the minimization problem for the damage effect on the OAR
      was treated under the constraint that the radiation effect on the tumor is fixed.
      RESULTS: For an N-time fractionated irradiation regimen, the constraint of tumor
      lethality was described by an N-dimensional hypersphere. The total dose of the
      fractionated irradiations was considered for minimizing the damage effect on the
      OAR under the hypersphere condition. It was found that the advantage of
      hypofractionated or multifractionated irradiation therapies depends on the
      magnitude of the ratio of alpha/beta parameters for the OAR and tumor in the
      linear-quadratic model and the ratio of the dose for the OAR and tumor.
      CONCLUSIONS: Our mathematical method shows that multifractionated irradiation
      with a constant dose is better if the ratio of alpha/beta for the OAR and tumor
      is less than the ratio of the dose for the OAR and tumor, whereas
      hypofractionated irradiation is better otherwise.

PMID- 22417808
TI  - Proton beam therapy and concurrent chemotherapy for esophageal cancer.
AB  - PURPOSE: Proton beam therapy (PBT) is a promising modality for the management of
      thoracic malignancies. We report our preliminary experience of treating
      esophageal cancer patients with concurrent chemotherapy (CChT) and PBT (CChT/PBT)
      at MD Anderson Cancer Center. METHODS AND MATERIALS: This is an analysis of 62
      esophageal cancer patients enrolled on a prospective study evaluating normal
      tissue toxicity from CChT/PBT from 2006 to 2010. Patients were treated with
      passive scattering PBT with two- or three-field beam arrangement using 180 to 250
      MV protons. We used the Kaplan-Meier method to assess time-to-event outcomes and
      compared the distributions between groups using the log-rank test. RESULTS: The
      median follow-up time was 20.1 months for survivors. The median age was 68 years
      (range, 38-86). Most patients were males (82%) who had adenocarcinomas (76%) and
      Stage II-III disease (84%). The median radiation dose was 50.4 Gy (RBE [relative
      biologic equivalence]) (range, 36-57.6). The most common grade 2 to 3 acute
      toxicities from CChT/PBT were esophagitis (46.8%), fatigue (43.6%), nausea
      (33.9%), anorexia (30.1%), and radiation dermatitis (16.1%). There were two cases
      of grade 2 and 3 radiation pneumonitis and two cases of grade 5 toxicities. A
      total of 29 patients (46.8%) received preoperative CChT/PBT, with one
      postoperative death. The pathologic complete response (pCR) rate for the surgical
      cohort was 28%, and the pCR and near CR rates (0%-1% residual cells) were 50%.
      While there were significantly fewer local-regional recurrences in the
      preoperative group (3/29) than in the definitive CChT/PBT group (16/33) (log-rank
      test, p = 0.005), there were no differences in distant metastatic (DM)-free
      interval or overall survival (OS) between the two groups. CONCLUSIONS: This is
      the first report of patients treated with PBT/CChT for esophageal cancer. Our
      data suggest that this modality is associated with a few severe toxicities, but
      the pathologic response and clinical outcomes are encouraging. Prospective
      comparison with more traditional approach is warranted.

PMID- 22417810
TI  - Rectification of terahertz radiation in semiconductor superlattices in the
      absence of domains.
AB  - We study theoretically the dynamical rectification of a terahertz AC electric
      field, i.e. the DC current and voltage response to the incident radiation, in
      strongly coupled semiconductor superlattices. We address the problem of stability
      against electric field domains: a spontaneous DC voltage is known to appear
      exactly for parameters for which a spatially homogeneous electron distribution is
      unstable. We show that by applying a weak direct current bias the rectifier can
      be switched from a state with zero DC voltage to one with a finite voltage in
      full absence of domains. The switching occurs near the conditions of dynamical
      symmetry breaking of an unbiased semiconductor superlattice. Therefore our scheme
      allows for the generation of DC voltages that would otherwise be unreachable due
      to domain instabilities. Furthermore, for realistic, highly doped wide miniband
      superlattices at room temperature, the generated DC field can be nearly
      quantized, that is, be approximately proportional to an integer multiple of
      homega/ea where a is the superlattice period and omega is the AC field frequency.

PMID- 22417811
TI  - Morphology controlled fabrication and ferroelectric properties of vertically
      aligned one-dimensional lead titanate nanoarrays.
AB  - Vertically aligned nanowires and highly uniform nanoporous array thin films of
      PbTiO(3) are synthesized by varying anodic oxidation conditions of Ti foil
      followed by hydrothermal reaction in an aqueous Pb(II) acetate trihydrate
      solution. As-synthesized samples have single crystalline nanowire structure and
      polycrystalline nanoporous structure, although both are pure PbTiO(3) with a
      tetragonal phase. The structure of intermediate TiO(2) films obtained from
      different anodic oxidation conditions determines the structure of the product
      PbTiO(3). The relationships between these morphological structures and
      ferroelectric properties are investigated. Piezoresponse force microscopy reveals
      that both these films show ferroelectricity with clear phase contrast and well
      defined hysteresis loops. The saturated longitudinal piezoelectric coefficient
      field (E(c)) of the nanowire sample is smaller than that of nanoporous thin film.
      Thus, polarization of nanowire thin film is larger in magnitude and easier to
      flip than that of nanoporous film.

PMID- 22417809
TI  - Proteomic analysis of acquired tamoxifen resistance in MCF-7 cells reveals
      expression signatures associated with enhanced migration.
AB  - INTRODUCTION: Acquired tamoxifen resistance involves complex signaling events
      that are not yet fully understood. Successful therapeutic intervention to delay
      the onset of hormone resistance depends critically on mechanistic elucidation of
      viable molecular targets associated with hormone resistance. This study was
      undertaken to investigate the global proteomic alterations in a tamoxifen
      resistant MCF-7 breast cancer cell line obtained by long term treatment of the
      wild type MCF-7 cell line with 4-hydroxytamoxifen (4-OH Tam). METHODS: We
      cultured MCF-7 cells with 4-OH Tam over a period of 12 months to obtain the
      resistant cell line. A gel-free, quantitative proteomic method was used to
      identify and quantify the proteome of the resistant cell line. Nano-flow high
      performance liquid chromatography coupled to high resolution Fourier transform
      mass spectrometry was used to analyze fractionated peptide mixtures that were
      isobarically labeled from the resistant and control cell lysates. Real time
      quantitative PCR and Western blots were used to verify selected proteomic
      changes. Lentiviral vector transduction was used to generate MCF-7 cells stably
      expressing S100P. Online pathway analysis was performed to assess proteomic
      signatures in tamoxifen resistance. Survival analysis was done to evaluate
      clinical relevance of altered proteomic expressions. RESULTS: Quantitative
      proteomic analysis revealed a wide breadth of signaling events during transition
      to acquired tamoxifen resistance. A total of 629 proteins were found
      significantly changed with 364 up-regulated and 265 down-regulated. Collectively,
      these changes demonstrated the suppressed state of estrogen receptor (ER) and ER
      regulated genes, activated survival signaling and increased migratory capacity of
      the resistant cell line. The protein S100P was found to play a critical role in
      conferring tamoxifen resistance and enhanced cell motility. CONCLUSIONS: Our data
      demonstrate that the adaptive changes in the proteome of tamoxifen resistant
      breast cancer cells are characterized by down-regulated ER signaling, activation
      of alternative survival pathways, and enhanced cell motility through regulation
      of the actin cytoskeleton dynamics. Evidence also emerged that S100P mediates
      acquired tamoxifen resistance and migration capacity.

PMID- 22417812
TI  - Fiscal decentralisation and infant mortality rate: the Colombian case.
AB  - There is a paucity of research analysing the influence of fiscal decentralisation
      on health outcomes. Colombia is an interesting case study, as health expenditure
      there has been decentralising since 1993, leading to an improvement in health
      care insurance. However, it is unclear whether fiscal decentralisation has
      improved population health. We assess the effect of fiscal decentralisation of
      health expenditure on infant mortality rates in Colombia. Infant mortality rates
      for 1080 municipalities over a 10-year period (1998-2007) were related to fiscal
      decentralisation by using an unbalanced fixed-effect regression model with robust
      errors. Fiscal decentralisation was measured as the locally controlled health
      expenditure as a proportion of total health expenditure. We also evaluated the
      effect of transfers from central government and municipal institutional capacity.
      In addition, we compared the effect of fiscal decentralisation at different
      levels of municipal poverty. Fiscal decentralisation decreased infant mortality
      rates (the elasticity was equal to -0.06). However, this effect was stronger in
      non-poor municipalities (-0.12) than poor ones (-0.081). We conclude that
      decentralising the fiscal allocation of responsibilities to municipalities
      decreased infant mortality rates. However, this improved health outcome effect
      depended greatly on the socio-economic conditions of the localities. The policy
      instrument used by the Health Minister to evaluate municipal institutional
      capacity in the health sector needs to be revised.

PMID- 22417813
TI  - Results from an online computer-tailored weight management intervention for
      overweight adults: randomized controlled trial.
AB  - BACKGROUND: Prevention of weight gain has been suggested as an important strategy
      in the prevention of obesity and people who are overweight are a specifically
      important group to target. Currently there is a lack of weight gain prevention
      interventions that can reach large numbers of people. Therefore, we developed an
      Internet-delivered, computer-tailored weight management intervention for
      overweight adults. The focus of the intervention was on making small (100 kcal
      per day), but sustained changes in dietary intake (DI) or physical activity (PA)
      behaviors in order to maintain current weight or achieve modest weight loss. Self
      regulation theory was used as the basis of the intervention. OBJECTIVE: This
      study aims to evaluate the efficacy of the computer-tailored intervention in
      weight-related anthropometric measures (Body Mass Index, skin folds and waist
      circumference) and energy balance-related behaviors (physical activity; intake of
      fat, snacks and sweetened drinks) in a randomized controlled trial. METHODS: The
      tailored intervention (TI) was compared to a generic information website (GI).
      Participants were 539 overweight adults (mean age 47.8 years, mean Body Mass
      Index (BMI) 28.04, 30.9% male, 10.7% low educated) who where recruited among the
      general population and among employees from large companies by means of
      advertisements and flyers. Anthropometric measurements were measured by trained
      research assistants at baseline and 6-months post-intervention. DI and PA
      behaviors were assessed at baseline, 1-month and 6-month post-intervention, using
      self-reported questionnaires. RESULTS: Repeated measurement analyses showed that
      BMI remained stable over time and that there were no statistically significant
      differences between the study groups (BMI: TI=28.09, GI=27.61, P=.09). Similar
      results were found for waist circumference and skin fold thickness. Amount of
      physical activity increased and intake of fat, snacks and sweetened drinks
      decreased during the course of the study, but there were no differences between
      the study groups (eg, fat intake: TI=15.4, GI=15.9, P=.74). The first module of
      the tailored intervention was visited by almost all participants, but only 15%
      completed all four modules of the tailored intervention, while 46% completed the
      three modules of the general information intervention. The tailored intervention
      was considered more personally relevant (TI=3.20, GI=2.83, P=.001), containing
      more new information (TI=3.11, GI=2.73, P=.003) and having longer texts (TI=3.20,
      GI=3.07, P=.01), while there were no group differences on other process measures
      such as attractiveness and comprehensibility of the information (eg, attractive
      design: TI=3.22, GI=3.16, P=.58). CONCLUSIONS: The online, computer-tailored
      weight management intervention resulted in changes in the desired direction, such
      as stabilization of weight and improvements in dietary intake, but the
      intervention was not more effective in preventing weight gain or modifying
      dietary and physical activity behaviors than generic information. A possible
      reason for the absence of intervention effects is sub-optimal use of the
      intervention and the self-regulation components. Further research is therefore
      needed to gain more insight into how the intervention and exposure to its
      contents can be improved. TRIAL REGISTRATION: NTR1862;
      http://apps.who.int/trialsearch/trial.aspx?trialid=NTR1862.

PMID- 22417814
TI  - Biosensing of reactive intermediates produced by the photocatalytic activities of
      titanium dioxide nanoparticles.
AB  - The development of an enzyme based biosensing method is described for evaluating
      the toxicity of solutions treated by titanium dioxide photocatalysis. The method
      is based on the potential of rat liver microsomal glutathione transferase ability
      (mGST) to get enhanced in the conditions of chemical and oxidative toxicity.
      Phenol is taken as a model pollutant due to its toxicity and prevalence in
      industrial processes. Chemical analysis of the parent compound, products and
      acute toxicity assays using the mGST activity, were conducted during and after
      the various photocatalytic treatments. The maximum mGST activity was observed
      from 60 and 120 min treated samples. This post-treatment toxicity might be due to
      toxic phenolic products, which may include p-benzoquinone, hydroquinone,
      benzenetriol and other intermediates. The enzymatic activity pattern observed
      after photocatalytic treatment corresponded well with the chemical degradation
      data obtained by HPLC-UV. The mGST assay seems to be an easy to use and promising
      approach for evaluating the effectiveness of wastewater treatment processes.

PMID- 22417815
TI  - Data-modelling and visualisation in chronic kidney disease (CKD): a step towards
      personalised medicine.
AB  - BACKGROUND: Personalised medicine involves customising management to meet
      patients' needs. In chronic kidney disease (CKD) at the population level there is
      steady decline in renal function with increasing age; and progressive CKD has
      been defined as marked variation from this  rate of decline. OBJECTIVE: To create
      visualisations of individual patient's renal function and display smoothed trend
      lines and confidence intervals for their renal function and other important co
      variants. METHOD: Applying advanced pattern recognition techniques developed  in
      biometrics to routinely collected primary care data collected as part of the
      Quality Improvement in Chronic Kidney Disease (QICKD) trial. We plotted trend
      lines, using regression, and confidence intervals for individual patients. We
      also created a visualisation which allowed renal function  to be compared with
      six other covariants: glycated haemoglobin (HbA1c), body mass index (BMI), BP,
      and therapy. The outputs were reviewed by an expert panel. RESULTS: We
      successfully extracted and displayed data. We demonstrated that estimated
      glomerular filtration (eGFR) is a noisy  variable, and showed that a large number
      of people would exceed the 'progressive CKD' criteria. We created a data display
      that could be readily automated. This display was well received by our expert
      panel but requires extensive development before testing in a clinical setting.
      CONCLUSIONS: It is feasible to utilise data visualisation methods developed in
      biometrics to look at CKD data. The criteria for defining 'progressive CKD' need
      revisiting, as many patients exceed them. Further development work and testing is
      needed to explore whether this type of data modelling and visualisation  might
      improve patient care.

PMID- 22417816
TI  - Leveraging electronic health records to support chronic disease management: the
      need for temporal data views.
AB  - BACKGROUND: The ageing population worldwide is increasingly acquiring multiple
      chronic diseases. The complex management of chronic diseases could be improved
      with electronic health records (EHRs) tailored to chronic disease care, but most
      EHRs in use today do not adequately support  longitudinal data management. A key
      aspect of chronic disease management is that it takes place over long periods,
      but the way that most EHRs display longitudinal data makes it difficult to trend
      changes over time and slows providers as they review each patient's unique
      course. METHODS: We present five clinical scenarios illustrating longitudinal
      data needs in complex chronic disease management. These scenarios may function as
      example cases for software development. OUTPUTS: For each scenario, we describe
      and illustrate improvements in temporal data views. Two potential  solutions are
      visualisation for numerical data and disease-oriented text summaries for non
      numerical data. CONCLUSIONS: We believe that development and widespread
      implementation of improved temporal data views in EHRs will improve the
      efficiency and quality of chronic disease management  in primary care.

PMID- 22417817
TI  - Mismatch between the prevalence of overweight and obese children and adolescents
      and recording in electronic health records: a cross-sectional study.
AB  - BACKGROUND: The prevalence of obesity has increased dramatically in recent years.
      An electronic health record (EHR) can be used to identify and manage overweight
      and obesity by providing timely information. OBJECTIVE: To estimate the
      prevalence of overweight and obesity  using anthropometric data from an EHR and
      to compare it with the frequency of diagnoses of 'overweight' and 'obesity'
      registered by pediatricians. METHODS: Cross-sectional, descriptive analytical
      study from a sample of records from children aged between 2 and 19 years who had
      at  least one well-child visit registered in the EHR over the 24-month period
      between 2007 and 2008. The record of a diagnosis of overweight or obesity by
      physicians was compared with estimations based on body mass index (BMI; World
      Health Organization Growth Reference Data). RESULTS: Of 14 743 patients aged 2-19
      years, 22.1% were overweight and 9.8% were obese. By contrast, a diagnosis of
      overweight was registered in the EHR for 3.3% of patients, with a figure of 1.1%
      for obesity. The prevalence of overweight/obesity was lower in adolescents than
      in children and  preschoolers. Based on BMI cut-off points, we found that only
      11.5% of the overweight or obese patients had these diagnoses registered in the
      EHR. Referral to a nutritionist or endocrinolist, and the frequency of selected
      laboratory tests based on BMI categories vary between 11.8 and 52.5%. CONCLUSION:
      An EHR can contribute to the identification of a population at risk when there is
      a sub-registry of these diagnoses by primary care physicians.

PMID- 22417818
TI  - Identification of patients with neuropathic pain using electronic primary care
      records.
AB  - BACKGROUND: Chronic neuropathic pain is a common condition which is challenging
      to treat. Many people with neuropathic pain are managed in the community, so
      primary care records may allow more appropriate subjects to be recruited for
      clinical studies. OBJECTIVE: We  investigated whether primary care records can be
      used to identify patients with diseases associated with neuropathic pain. METHOD:
      We analysed demographic, diagnostic and prescribing data from over 100 000
      primary care electronic patient records in one part of London, UK. RESULTS: The
      prevalence of diagnoses associated with chronic neuropathic pain was 13 per 1000,
      with the elderly, women and white patients experiencing the greatest burden of
      disease. CONCLUSION: Computerised health records offer an excellent opportunity
      to improve the identification of patients  for clinical research in complex
      conditions like chronic neuropathic pain. To make full use of data from these
      records, standardisation of clinical coding and consensus on diagnostic criteria
      are needed.

PMID- 22417819
TI  - Study of electronic prescribing rates and barriers identified among providers
      using electronic health records in New York City.
AB  - BACKGROUND: Increased electronic prescribing (eRx) rates have the potential to
      prevent errors, increase patient safety, and curtail fraud. US Federal meaningful
      use guidelines require at least a 40% electronic prescribing rate. OBJECTIVE: We
      evaluated eRx rates among  primary care providers in New York City in order to
      determine trends as well as identify any obstacles to increased eRx rates
      required by meaningful use guidelines. METHODS: The data we analysed included
      automatic electronic data transmissions from providers enrolled in the Primary 
      Care Information Project (PCIP) from 1 January 2009 to 1 July 2010 and follow-up
      telephone calls to a subset of these providers to identify potential barriers to
      increased eRx usage. RESULTS: Over the course of the study, these providers
      increased the eRx rate from 12.9 to 27.5%,  with an average rate of 24.1%.
      Conversations with providers identified their perceived barriers to increased eRx
      use as primarily patient preference for paper prescriptions and a belief that
      many pharmacies do not accept eRx. CONCLUSIONS: The data gathered from our
      providers indicate  that there is an increasing trend in the eRx rate to 27.5% by
      July 2010, but still short of the 40% meaningful use level. However, obstacles to
      increased rates remain primarily providers' belief that many patients prefer
      paper prescriptions and many pharmacies are not yet prepared to accept 
      electronic prescriptions.

PMID- 22417820
TI  - Complex adaptive systems: a tool for interpreting responses and behaviours.
AB  - BACKGROUND: Quality improvement is a priority for health services worldwide.
      There are many barriers to implementing change at the locality level and
      misinterpreting responses and behaviours can effectively block change. Electronic
      health records will influence the means by which  knowledge and information are
      generated and sustained among those operating quality improvement programmes.
      OBJECTIVE: To explain how complex adaptive system (CAS) theory provides a useful
      tool and new insight into the responses and behaviours that relate to quality
      improvement programmes  in primary care enabled by informatics. METHODS: Case
      studies in two English localities who participated in the implementation and
      development of quality improvement programmes. The research strategy included
      purposefully sampled case studies, conducted within a social constructionist 
      ontological perspective. RESULTS: Responses and behaviours of quality improvement
      programmes in the two localities include both positive and negative influences
      associated with a networked model of governance. Pressures of time, resources and
      workload are common issues, along with  the need for education and training about
      capturing, coding, recording and sharing information held within electronic
      health records to support various information requirements. CONCLUSIONS: Primary
      care informatics enables information symmetry among those operating quality
      improvement  programmes by making some aspects of care explicit, allowing
      consensus about quality improvement priorities and implementable solutions.

PMID- 22417821
TI  - Primary care provider perceptions and use of a novel medication reconciliation
      technology.
AB  - BACKGROUND: Although medication reconciliation (MR) can reduce medication
      discrepancies, it is challenging to operationalise. Consequently, we developed a
      health information technology (HIT) to collect a patient medication history and
      make it available to the primary care (PC)  provider. We deployed a self-service
      kiosk in a PC clinic that permits patients to indicate a medication adherence
      history. Patient responses are immediately viewable in the legacy electronic
      health record. This paper describes a survey developed to assess PC provider
      perceptions of our HIT  and HIT implementation effectiveness. METHODS: We
      developed and administered a survey to all PC providers to assess technology
      implementation effectiveness. The survey included scales measuring (1) user
      attitudes towards MR, (2) perceptions of our HIT and (3) the local organisational
      climate for implementation. We also assessed the consistency and quality of tool
      use. RESULTS: Nearly 90% of PC providers responded to the survey and 58%
      indicated that they were familiar with the technology and had seen the tool
      output. Most providers believed that MR represented  an important safety
      intervention, although 43% did not believe that they had the necessary resources
      to manage discrepancies. Composite scale scores for the 58% of respondents
      familiar with the HIT indicate that the majority favoured our tool over usual
      care. However, composite scale scores  suggest that the climate for
      implementation at our facility was suboptimal. Overall, the quality and
      consistency of tool use among providers was very heterogeneous. CONCLUSIONS: A
      patient self-service kiosk offers an efficient mechanism to collect a medication
      adherence history;  provider survey responses indicate that they appreciated and
      used the MR kiosk output. Nonetheless, opportunities exist to improve data
      displays and embed decision support to facilitate discrepancy management.

PMID- 22417822
TI  - Development of a database for cervical cytology reports.
AB  - BACKGROUND: Cervical cancer is an important cause of female mortality. Its
      incidence, however, has been drastically reduced by early detection using the
      Papanicolaou screening method. As a result of the widespread use of this method,
      a large amount of cytological information  has to be stored, printed and handled
      efficiently. This paper describes a database system designed to manage
      information from studies of cervical cytology, which was developed at the Faculty
      of Medical Sciences, National University of La Plata, Argentina. METHODS:
      Information needs  were assessed by interviews with physicians and analysis of
      cytology reports. The database was developed using MS Access 2007. RESULTS: The
      database is designed to collect, display, sort and print patient demographics,
      clinical data and cytological studies. Diagnoses can be stored  either as
      international classifications or as free text. The database contains 45 tables
      and 50 forms for data entry, editing and display. This information can be
      exported to spreadsheets and statistical packages. CONCLUSION: This database
      gives users easy access to patients' cytological  diagnoses and provides a useful
      tool for physicians and public health researchers.

PMID- 22417824
TI  - Needle exchange and the geography of survival in the South Bronx.
AB  - This paper explores the position of needle exchange programmes (NEPs) in the
      "geography of survival" in the South Bronx neighbourhood of New York City.
      Stemming the spread of HIV through the provision of sterile injecting equipment,
      needle exchange promotes the survival of injection drug users (IDUs) in the
      starkest sense; yet NEPs also attract a diverse population of service users whose
      attendance is not necessarily related to drugs. This paper locates NEPs among a
      larger constellation of social services accessed by residents of poor
      neighbourhoods, including injection drug users, the homeless, the hungry, and
      those in need of medical services or just safe space. Drawing on ethnographic and
      interview data from a needle exchange in the South Bronx, I describe how both
      IDUs and others employed the organisation to make ends meet, elaborating four
      "off-label" usages of needle exchange: as a place to obtain basic necessities, as
      a source of income, as a safe space, and as a site of social contact. As harm
      reduction in the United States moves towards an increasingly clinical model of
      care, this paper considers these latent functions of needle exchange within the
      context of a larger struggle over the content and meaning of harm reduction
      services. By themselves, NEPs are clearly an unsatisfactory solution to the
      economic and political circumstances that drive a variety of individuals through
      their doors; yet, in a country that lacks a comprehensive welfare system, needle
      exchange arguably represents an important thread within a social safety net that
      is being woven from the ground up. This study may be used to argue for a
      (re)expanded mission for harm reduction in the United States, in the face of
      constant moves to narrow its mandate and reduce its budget.

PMID- 22417823
TI  - "I'm not afraid of those ones just 'cause they've been prescribed": perceptions
      of risk among illicit users of pharmaceutical opioids.
AB  - BACKGROUND: There has been a rise in the illicit use of pharmaceutical opioids
      ("pain pills") in the United States. Conducted with young adult non-medical users
      of pharmaceutical opioids, this study uses qualitative methods and cultural
      consensus analysis to describe risk perceptions associated with pharmaceutical
      opioids and to determine patterns of cultural sharing and intra-cultural
      variation of these views. METHODS: The qualitative sub-sample (n=47) was selected
      from a larger sample of 396 young adults (18-23 years old), who were
      participating in a natural history study of illicit pharmaceutical opioid use.
      Qualitative life history interviews, drug ranking task, and cultural consensus
      analysis were used to elicit participant views about risks and harms associated
      with pain pills and other drugs, as well as alcohol and tobacco. RESULTS:
      Cultural consensus analysis revealed that the participants shared a single
      cultural model of drug risks, but the level of agreement decreased with the
      increasing range of drugs ever used. Further, those with more extensive drug use
      histories differed from less "experienced" users in their views about OxyContin
      and some other drugs. Overall, pain pills were viewed as addicting and
      potentially deadly substances, but these properties were linked to the patterns
      and methods of use, as well as characteristics of an individual user. Further,
      risks associated with pharmaceutical opioids were further curtailed because they
      "came from the doctor," and thus had a legitimate aspect to their use.
      CONCLUSIONS: This study highlights potential problems with universal approaches
      to substance use prevention and intervention among young people since such
      approaches ignore the fact that substance use education messages may be
      experienced differently depending on an individual's drug use history and his/her
      perceptions of drug risks. Findings reported here may be useful in the
      development of prevention and intervention programs aimed at reducing the harm
      associated with illicit use of pain pills.

PMID- 22417825
TI  - Well-written but misplaced: a response to Barrett's comment.

PMID- 22417826
TI  - Distribution and histologic effects of intravenously administered amorphous
      nanosilica particles in the testes of mice.
AB  - Amorphous nanosilica particles (nSP) are being utilized in an increasing number
      of applications such as medicine, cosmetics, and foods. The reduction of the
      particle size to the nanoscale not only provides benefits to diverse scientific
      fields but also poses potential risks. Several reports have described the in vivo
      and in vitro toxicity of nSP, but few studies have examined their effects on the
      male reproductive system. The aim of this study was to evaluate the testicular
      distribution and histologic effects of systemically administered nSP. Mice were
      injected intravenously with nSP with diameters of 70 nm (nSP70) or conventional
      microsilica particles with diameters of 300 nm (nSP300) on two consecutive days.
      The intratesticular distribution of these particles 24h after the second
      injection was analyzed by transmission electron microscopy. nSP70 were detected
      within sertoli cells and spermatocytes, including in the nuclei of spermatocytes.
      No nSP300 were observed in the testis. Next, mice were injected intravenously
      with 0.4 or 0.8 mg nSP70 every other day for a total of four administrations.
      Testes were harvested 48 h and 1 week after the last injection and stained with
      hematoxylin-eosin for histologic analysis. Histologic findings in the testes of
      nSP70-treated mice did not differ from those of control mice. Taken together, our
      results suggest that nSP70 can penetrate the blood-testis barrier and the nuclear
      membranes of spermatocytes without producing apparent testicular injury.

PMID- 22417827
TI  - Expression of prohibitins on the surface of activated T cells.
AB  - Prohibitins (prohibitin-1 and -2) comprise a family of highly conserved proteins
      that are mainly localized to mitochondria. Recent studies showed that prohibitins
      are up-regulated upon T cell activation and play an essential role in maintaining
      mitochondrial homeostasis. In the present study, we found that a considerable
      proportion of prohibitin-1 and -2 induced in response to T cell activation was
      expressed on the surface of activated T cells. When mouse and human T cells were
      stimulated with PMA and ionomycin, prohibitins expressed on the cell surface were
      increased significantly, peaking at 48 h after stimulation. Stimulation of mouse
      T cells with anti-CD3 and anti-CD28 antibodies also remarkably induced the cell
      surface expression of prohibitins. Their expression on the cell surface was also
      detected in T cell leukemia cells such as Jurkat cells. In Jurkat cells,
      prohibitin-1 and -2 were co-localized with CD3 on the cell surface, and anti-CD3
      antibody-induced signaling, the MAP kinase cascade, was inhibited on treatment
      with protein A magnetic beads co-conjugated with anti-CD3 antibody and anti
      prohibitin-1 or anti-prohibitin-2 antibody. These results suggest that
      prohibitins expressed on the surface of activated T cells are involved in the T
      cell receptor-mediated signaling cascade.

PMID- 22417828
TI  - Cdc25A promotes cell survival by stimulating NF-kappaB activity through IkappaB
      alpha phosphorylation and destabilization.
AB  - Cell division cycle 25A (Cdc25A), a dual specificity protein phosphatase,
      exhibits anti-apoptotic activity, but the underlying molecular mechanisms are
      poorly characterized. Here we report that Cdc25A inhibits cisplatin-induced
      apoptotic cell death by stimulating nuclear factor-kappa B (NF-kappaB) activity.
      In HEK-293 cells, Cdc25A decreased protein level of inhibitor subunit kappa B
      alpha (Ikappa-Balpha) in association with increased serine 32-phosphorylation,
      followed by stimulation of transcriptional activity of NF-kappaB. Inhibition of
      NF-kappaB activity by chemical inhibitor or overexpression of Ikappa-Balpha in
      Cdc25A-elevated cancer cells resistant to cisplatin improved their sensitivity to
      cisplatin-induced apoptosis. Our data show for the first time that Cdc25A has an
      important physiological role in NF-kappaB activity regulation and it may be an
      important survival mechanism of cancer cells.

PMID- 22417829
TI  - Detection of JWH-018 and JWH-073 by UPLC-MS-MS in postmortem whole blood
      casework.
AB  - Synthetic cannabinoids have been detected in various herbal blends sold legally
      in convenience stores, smoke shops, and on the Internet. Many of these compounds
      have extreme forensic significance. We developed and validated a rapid ultra
      performance liquid chromatography-tandem mass spectrometry method for the
      determination of trace concentrations of two of these compounds, JWH-018 and JWH
      073, in human blood. Samples underwent liquid-liquid extraction at pH 10.2 into
      ethyl ether. Tandem mass spectrometry was performed in positive electrospray
      ionization mode with multiple reaction monitoring using two transitions and one
      calculated ion transition ratio for each analyte. Deuterated analogs were used as
      internal standards. Total run time was 2.6 min. The linear dynamic range was 0.05
      50 ng/mL with a limit of detection of 0.01 ng/mL for each analyte. Intra-run
      imprecision (at two different concentration levels, 2 and 8 ng/mL) was 3.9-10.3%
      for JWH-018 and 3.5-6.2% for JWH-073. Inter-run imprecision was 6.5-7.2% for JWH
      018 and 4.8-5.5% for JWH-073. Intra-run accuracy was 95.9-112.7% for JWH-018 and
      92.6-104.7% for JWH-073. Inter-run accuracy was 99.1-107.0% for JWH-018 and 97.7
      102.0% for JWH-073. Carryover, exogenous drug interferences, ion suppression and
      matrix selectivity were also assessed. The method has been applied to postmortem
      forensic casework received by the laboratory and has proven to be robust and
      reliable. Concentrations of authentic samples have ranged from 0.1-199 ng/mL for
      JWH-018 and 0.1-68.3 ng/mL for JWH-073.

PMID- 22417830
TI  - Estimating the measurement uncertainty in forensic blood alcohol analysis.
AB  - For many reasons, forensic toxicologists are being asked to determine and report
      their measurement uncertainty in blood alcohol analysis. While understood
      conceptually, the elements and computations involved in determining measurement
      uncertainty are generally foreign to most forensic toxicologists. Several
      established and well-documented methods are available to determine and report the
      uncertainty in blood alcohol measurement. A straightforward bottom-up approach is
      presented that includes: (1) specifying the measurand, (2) identifying the major
      components of uncertainty, (3) quantifying the components, (4) statistically
      combining the components and (5) reporting the results. A hypothetical example is
      presented that employs reasonable estimates for forensic blood alcohol analysis
      assuming headspace gas chromatography. These computations are easily employed in
      spreadsheet programs as well. Determining and reporting measurement uncertainty
      is an important element in establishing fitness-for-purpose. Indeed, the demand
      for such computations and information from the forensic toxicologist will
      continue to increase.

PMID- 22417831
TI  - Determination of opiates in whole blood and vitreous humor: a study of the matrix
      effect and an experimental design to optimize conditions for the enzymatic
      hydrolysis of glucuronides.
AB  - Undoubtedly, whole blood and vitreous humor have been biological samples of great
      importance in forensic toxicology. The determination of opiates and their
      metabolites has been essential for better interpretation of toxicological
      findings. This report describes the application of experimental design and
      response surface methodology to optimize conditions for enzymatic hydrolysis of
      morphine-3-glucuronide and morphine-6-glucuronide. The analytes (free morphine, 6
      acetylmorphine and codeine) were extracted from the samples using solid-phase
      extraction on mixed-mode cartridges, followed by derivatization to their
      trimethylsilyl derivatives. The extracts were analysed by gas chromatography-mass
      spectrometry with electron ionization and full scan mode. The method was
      validated for both specimens (whole blood and vitreous humor). A significant
      matrix effect was found by applying the F-test. Different recovery values were
      also found (82% on average for whole blood and 100% on average for vitreous
      humor). The calibration curves were linear for all analytes in the concentration
      range of 10-1,500 ng/mL. The limits of detection ranged from 2.0 to 5.0 ng/mL.
      The method was applied to a case in which a victim presented with a previous
      history of opiate use.

PMID- 22417832
TI  - Simultaneous analysis of strychnine and brucine and their major metabolites by
      liquid chromatography-electrospray ion trap mass spectrometry.
AB  - A liquid chromatography-electrospray ionization-ion trap mass spectrometry (LC
      ESI-ITMS) method was developed for the simultaneous analysis of strychnine,
      brucine and their major metabolites. Strychnine and brucine were individually
      incubated with rat liver S9 fraction. The incubation samples were pooled together
      and analyzed with LC-ESI-ITMS in positive ion and full-scan detection mode. The
      calibration curves of strychnine and brucine in rat liver showed good linearity
      in ranges of 0.020 to 8.0 ug/mL for strychnine and 0.020 to 8.5 ug/mL for
      brucine. The limits of detections were both 0.008 ug/mL and the recoveries were
      88.3 and 83.2% for strychnine and brucine, respectively. Two metabolites were
      identified as strychnine N-oxide and brucine N-oxide by comparing the molecular
      mass, retention time, full-scan mass spectra, tandem MS and MS(3) spectra with
      those of strychnine and brucine. The developed method provided high sensitivity
      and selectivity for the determination of poisonous alkaloids and their major
      metabolites and can be applied in the determination of samples in forensic and
      clinically toxicological cases.

PMID- 22417833
TI  - Postmortem carisoprodol and meprobamate concentrations in blood and liver: lack
      of significant redistribution.
AB  - Carisoprodol is a therapeutic and occasionally abused centrally acting muscle
      relaxant. We compare central blood and liver concentrations of carisoprodol and
      the metabolite meprobamate to concentrations in peripheral blood in 11 medical
      examiner cases. Specimens were initially screened for alcohol and simple
      volatiles by gas chromatography (GC)-flame ionization detection headspace
      analysis, enzyme-linked immunosorbent array for drugs of abuse, and therapeutic
      drugs by GC-mass spectrometry (MS). Carisoprodol, when detected by the
      therapeutic drug screen, was confirmed and quantified by a specific GC-MS
      procedure. The results suggest that when ingested with other medications,
      carisoprodol may be a contributing factor in death, even when present at
      therapeutic concentrations. Considering the cases studied, together with
      previously published therapeutic and fatal concentrations, blood carisoprodol
      concentrations greater than 15 mg/L and liver concentrations greater than 50
      mg/kg may be considered excessive and potentially fatal. Carisoprodol central
      blood to peripheral blood ratios averaged 1.31 + 0.33 (mean +/- standard
      deviation), and liver to peripheral blood, 2.83 +/- 1.51. Meprobamate central
      blood to peripheral blood ratios averaged 0.92 +/- 0.22, and liver to peripheral
      blood, 1.25 +/- 0.69. The low liver to peripheral blood ratio (less than 5),
      taken together with the low central blood to peripheral blood ratio, is an
      indicator that both carisoprodol and meprobamate lack the potential to exhibit
      postmortem redistribution.

PMID- 22417834
TI  - Fentanyl: toxic or therapeutic? Postmortem and antemortem blood concentrations
      after transdermal fentanyl application.
AB  - In forensic toxicology, several fatal intoxications with fentanyl have occurred
      in the recent past, but there are rare discussions in the literature of
      postmortem fentanyl blood concentrations subsequent to lethal and non lethal
      applications. To study this problem, we analyzed postmortem blood concentrations
      (vena femoralis) of 118 cases with therapeutic use of fentanyl and compared them
      with serum levels of 27 living persons after therapeutic administration of
      fentanyl patches (Durogesic). Basically, blood concentrations in postmortem
      specimens cannot be directly compared with in vivo serum levels: in our study, we
      observed that postmortem fentanyl blood concentrations were on average up to nine
      times higher than in vivo serum levels at the same dose. These differences could
      be explained by postmortem redistribution, but they were higher than expected on
      the basis of the physical and chemical properties of fentanyl alone. The special
      pharmacokinetics of the drug after long term transdermal application seem to play
      an important role in this phenomenon. In addition, there was no clear correlation
      between transdermal fentanyl dose and blood or serum concentrations, either
      antemortem or postmortem. Our study provides extensive data for postmortem
      peripheral blood concentrations after therapeutic non-fatal fentanyl patch
      application and demonstrates once more that in forensic toxicology, blood
      concentrations must be holistically interpreted with respect to all aspects of a
      case.

PMID- 22417835
TI  - Segmental hair analysis for 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid
      and the patterns of cannabis use.
AB  - Cannabis is the most widely abused drug in the world. The purpose of this study
      is to detect 11-nor-9-carboxy-Delta9-tetrahydrocannabinol (THCCOOH) in segmental
      hair and to evaluate the patterns of cannabis use. We investigated the
      relationship between the concentrations of THCCOOH in hair and the self-reported
      use data and the route of administration. For this purpose, the hair samples were
      washed, digested with 1 mL of 1 M NaOH at 85 degrees C for 30 min along with the
      internal standard, THCCOOH-d3 (2.5 pg/mg) and extracted in 2 mL of n-hexane-ethyl
      acetate (9:1) twice after adding 1 mL of 0.1N sodium acetate buffer (pH = 4.5)
      and 200 uL of acetic acid. The organic extract was transferred and evaporated and
      the mixture was derivatized with 50 uL of pentafluoropropionic anhydride and 25
      uL of pentafluoropropanol for 30 min at 70 degrees C. Reconstituted final extract
      was injected into the gas chromatography-tandem mass spectrometer operating in
      the negative chemical ionization mode. In segmental hair analysis, the
      concentrations of THCCOOH decreased from the proximal to distal segments. The
      concentrations of THCCOOH in hair and the self-reported dose and frequency of
      administration from cannabis users were not well correlated because of the low
      accuracy and reliability of the self-reported data. However, this study provides
      preliminary information on the dose and frequency of administration among
      cannabis users in our country.

PMID- 22417836
TI  - A new highly specific buprenorphine immunoassay for monitoring buprenorphine
      compliance and abuse.
AB  - Urine buprenorphine screening is utilized to assess buprenorphine compliance and
      to detect illicit use. Robust screening assays should be specific for
      buprenorphine without cross-reactivity with other opioids, which are frequently
      present in patients treated for opioid addiction and chronic pain. We evaluated
      the new Lin-Zhi urine buprenorphine enzyme immunoassay (EIA) as a potentially
      more specific alternative to the Microgenics cloned enzyme donor immunoassay
      (CEDIA) by using 149 urines originating from patients treated for chronic pain
      and opioid addiction. The EIA methodology offered specific detection of
      buprenorphine use (100%) (106/106) and provided superior overall agreement with
      liquid chromatography-tandem mass spectrometry, 95% (142/149) and 91% (135/149)
      using 5 ng/mL (EIA[5]) and 10 ng/mL (EIA[10]) cutoffs, respectively, compared to
      CEDIA, 79% (117/149). CEDIA generated 27 false positives, most of which were
      observed in patients positive for other opioids, providing an overall specificity
      of 75% (79/106). CEDIA also demonstrated interference from structurally unrelated
      drugs, chloroquine and hydroxychloroquine. CEDIA and EIA[5] yielded similar
      sensitivities, both detecting 96% (22/23) of positive samples from patients
      prescribed buprenorphine, and 88% (38/43) and 81% (35/43), respectively, of all
      positive samples (illicit and prescribed users). The EIA methodology provides
      highly specific and sensitive detection of buprenorphine use, without the
      potential for opioid cross-reactivity.

PMID- 22417837
TI  - Reactivity of commercial benzodiazepine immunoassays to phenazepam.
AB  - Phenazepam is a long acting benzodiazepine that is not controlled in Canada, the
      United States or many European countries. The abuse of phenazepam has gained
      recent attention due to the number of hospitalizations and fatalities resulting
      from overdose. The compound is relatively potent with recommended doses of 0.5
      1.0 mg, or 1/10th the recommended dose of diazepam, and is easy to obtain locally
      or from international suppliers via the internet. Increased risk of phenazepam
      overdose is attributed to its potency and the forms in which it is supplied.
      Individuals without scales or balances are prone to estimate dose amounts of
      powder visually, which can result in significant errors. The detection of
      phenazepam has been described using various methods including GC, GC/MS and
      LC/MS, but no data regarding the sensitivity of commercially available
      immunoassays exist. In this study, phenazepam-spiked urine samples were analyzed
      using five commercial instruments and two point of care devices. The
      concentrations of phenazepam required for detection ranged from 140-462 ng/mL,
      which is comparable to those of other benzodiazepines. Laboratorians and
      clinicians should be confident that phenazepam will be detected via most
      commercial drugs of abuse screens in patients after significant ingestion.

PMID- 22417838
TI  - Performance of a point-of-care device for oral fluid ketamine evaluated by a
      liquid chromatography-tandem mass spectrometry method.
AB  - The performance of a point-of-care device, the OratectXP Oral Fluid Drug Screen
      Device for Ketamine, was evaluated. The cutoff specification for the device was
      for ketamine at 15 ng/mL. A total of 72 authentic oral fluid samples were
      collected from volunteers at two local rehabilitation centers for clients with
      addiction to drugs of abuse. These samples were tested with the device for visual
      detection of ketamine and also measured by a liquid chromatography isotope
      dilution tandem mass spectrometry method for ketamine, norketamine and
      dehydronorketamine concentrations. Sensitivity of the device was 87.5% when
      tested by 24 authentic oral fluid samples with ketamine concentrations >= 15
      ng/mL. False positive rate of the device was 4.5%. Specificity of the device was
      97.9% when tested by 48 authentic oral fluid samples with ketamine concentrations
      < 15 ng/mL. False negative rate of the device was 6%. The overall efficiency of
      the device was 94%. According to the desirable acceptance criteria proposed by
      the "Driving Under the Influence of Drugs, Alcohol, and Medicines" project, the
      performance of the OratectXP was satisfactory and achieved the minimum standard
      for testing drivers under the influence of drugs. Furthermore, we propose the
      confirmation cutoff level for oral fluid ketamine to be at 25 ng/mL.

PMID- 22417839
TI  - Determination of carisoprodol and meprobamate in oral fluid.
AB  - The determination of carisoprodol and its metabolite meprobamate in oral fluid
      using solid-phase extraction and liquid chromatography with tandem mass spectral
      detection (LC-MS-MS) and its application to authentic specimens is described. The
      method employs collection of oral fluid with the Quantisal device, extraction
      using cation exchange/hydrophobic solid-phase columns, and LC-MS-MS in positive
      ion electrospray mode. The method was fully validated using various parameters,
      including selectivity, linearity, accuracy, intra-day and inter-day imprecision,
      drug recovery from the collection pad, limit of quantitation and matrix effects.
      The method was applied to both routine research specimens and an authentic
      specimen taken from an individual prescribed a daily dose of 350 mg carisoprodol
      following surgery.

PMID- 22417840
TI  - Atherosclerosis risk in HIV-infected patients: the influence of hepatitis C virus
      co-infection.
AB  - BACKGROUND: The influence of hepatitis C virus (HCV) infection on atherosclerosis
      risk in HIV-infected patients has not been adequately evaluated in real-life
      situations. OBJECTIVES AND METHODS: We compared indexes of early atherosclerosis
      evaluated by echo-Doppler ultrasound (presence of plaque in carotid or femoral
      arteries) in 18 HCV-HIV co-infected patients versus 22 HIV mono-infected
      patients. RESULTS: Prevalence of subclinical carotid plaque was significantly
      higher in HCV-HIV co-infected patients (p=0.04), despite of the fact LDL
      cholesterol and blood pressure (BP) were lower in the co-infected patients
      (p=0.003). HCV chronic infection (OR=10; IC: 1.5-72; p=0.02) was an independent
      risk factor. CONCLUSION: This cross sectional study suggests that HCV infection
      might be an independent cardiovascular risk factor in HCV-HIV co-infected
      patients. HCV infection might be considered as not only a liver infection but
      also as a metabolic disease in HIV patients, justifying regular cardiovascular
      surveillance.

PMID- 22417841
TI  - Effect of mutations in LDLR and PCSK9 genes on phenotypic variability in Tunisian
      familial hypercholesterolemia patients.
AB  - BACKGROUND: Autosomal dominant hypercholesterolemia (ADH) is commonly caused by
      mutations in the low-density lipoprotein (LDL) receptor gene (LDLR), in the
      apolipoprotein B-100 gene (APOB), or in the proprotein convertase subtilisin
      kexine 9 gene (PCSK9). ADH subjects carrying a mutation in LDLR present highly
      variable plasma LDL-cholesterol (LDL-C). This variability might be due to
      environmental factors or the effect of some modifying genes such as PCSK9 and
      APOE. AIMS: We investigated the molecular basis of thirteen Tunisian ADH families
      and attempted to determine the impact of PCSK9 and APOE gene variations on LDL
      cholesterol levels and on the variable phenotypic expression of the disease.
      METHODS AND RESULTS: Fifty six subjects were screened for mutations in the LDLR
      gene through direct sequencing. The causative mutation was found to segregate
      with the disease in each family and a new frameshift mutation, p.Met767CysfsX21,
      was identified in one family. The distribution of total- and LDL-cholesterol
      levels, adjusted for age and gender, among homozygous and heterozygous ADH
      patients varied widely. Within seven families, nine subjects presented low LDL
      cholesterol levels despite carrying a mutation in the LDLR gene. To identify the
      molecular actors underlying this phenotypic variability, the PCSK9 gene was
      screened using direct sequencing and/or enzymatic restriction analysis, and the
      apo E genotypes were determined. A new missense variation (p.Pro174Ser) in the
      PCSK9 gene was identified and characterized as a new putative loss-of-function
      mutation. CONCLUSION: Genetic variations in PCSK9 and APOE genes could explain
      only part of the variability observed in the phenotypic expression in Tunisian
      ADH patients carrying mutations in the LDLR gene. Other genetic variants and
      environmental factors very probably act to fully explain this phenotypic
      variability.

PMID- 22417842
TI  - Dual effects of statins therapy in systemic lupus erythematosus and SLE-related
      atherosclerosis: the potential role for regulatory T cells.
AB  - Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease associated
      with accelerated atherosclerosis independent of traditional risk factors.
      Statins, the 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase
      inhibitors, have been widely prescribed for hyperlipidemia, which could slow the
      atherosclerosis progression, and reduce cardiovascular disease events.
      Nonetheless, accumulated evidences suggested that statins exert immunomodulatory
      and anti-inflammatory functions independent of their lipid-lowering effects. By
      the virtue of pleiotropic immunomodulatory property, statins may be applied for
      the treatment of both autoimmunity and atherosclerosis in patients with SLE.
      Interestingly, it has been well documented that regulatory T cells (Tregs) are
      involved in the pathogenesis of SLE as well as atherosclerosis. Meanwhile,
      studies have shown that statins could induce augmented number of Tregs with
      increased functional inhibitory properties. Thus, we hypothesized that the effect
      of statins ameliorating lupus disease manifestations and lupus-mediated
      atherogenesis might be mediated, at least partly, via the activation of Tregs. To
      our knowledge, this is the first hypothesis focused on that Tregs might be
      involved in the immunomodulatory effect of statins on SLE and SLE-related
      atherosclerosis.

PMID- 22417843
TI  - Association of pericardial fat and coronary high-risk lesions as determined by
      cardiac CT.
AB  - OBJECTIVE: Pericardial adipose tissue (PAT) is a pathogenic fat depot associated
      with coronary atherosclerosis and cardiovascular events. We hypothesized that
      higher PAT is associated with coronary high-risk lesions as determined by cardiac
      CT. METHODS: We included 358 patients (38% female; median age 51 years) who were
      admitted to the ED with acute chest pain and underwent 64-slice CT angiography.
      The cardiac CT data sets were assessed for presence and morphology of CAD and
      PAT. Coronary high-risk lesions were defined as >50% luminal narrowing and at
      least two of the following characteristics: positive remodeling, low-density
      plaque, and spotty calcification. PAT was defined as any pixel with CT
      attenuation of -190 to -30 HU within the pericardial sac. RESULTS: Based on
      cardiac CT, 50% of the patients (n=180) had no CAD, 46% (n=165) had CAD without
      high-risk lesions, and 13 patients had CAD with high-risk lesions. The median PAT
      in patients with high-risk lesions was significantly higher compared to patients
      without high-risk lesions and without any CAD (151.9 [109.0-179.4]cm(3) vs. 110.0
      [81.5-137.4]cm(3), vs. 74.8 [58.2-111.7]cm(3), respectively p=0.04 and p<0.0001).
      These differences remained significant after adjusting for traditional risk
      factors including BMI (all p<0.05). The area under the ROC curve for the
      identification of high-risk lesions was 0.756 in a logistic regression model with
      PAT as a continuous predictor. CONCLUSION: PAT volume is nearly twice as high in
      patients with high-risk coronary lesions as compared to those without CAD. PAT
      volume is significantly associated with high risk coronary lesion morphology
      independent of clinical characteristics and general obesity.

PMID- 22417844
TI  - Humidified high flow nasal oxygen during respiratory failure in the emergency
      department: feasibility and efficacy.
AB  - OBJECTIVE: Heated and humidified high flow nasal cannula oxygen therapy (HFNC)
      represents a new alternative to conventional oxygen therapy that has not been
      evaluated in the emergency department (ED). We aimed to study its feasibility and
      efficacy in patients exhibiting acute respiratory  failure presenting to the ED.
      METHODS: Prospective, observational study in a university hospital's ED. Patients
      with acute respiratory failure requiring > 9 L/min oxygen or with ongoing
      clinical signs of respiratory distress despite oxygen therapy were included. The
      device of oxygen administration  was then switched from non-rebreathing mask to
      HFNC. Dyspnea, rated by the Borg scale and a visual analog scale, respiratory
      rate, and S(pO(2)) were collected before and 15, 30, and 60 min after beginning
      HFNC. Feasibility was assessed through caregivers' acceptance of the  device in
      terms of practicality and perceived effect on the subjects, evaluated by
      questionnaire. RESULTS: Seventeen subjects, median age 64 y (46-84.7 y), were
      studied. Pneumonia was the most common reason for oxygen therapy (n = 9). HFNC
      was associated with a significant decrease  in both dyspnea scores: Borg scale
      from 6 (5-7) to 3 (2-4) (P < .001), and visual analog scale from 7 (5-8) to 3 (1
      5) (P < .01). Respiratory rate decreased from 28 breaths/min (25-32 breaths/min)
      to 25 breaths/min (21-28 breaths/min)  (P < .001), and S(pO(2)) increased from
      90% (88.5-94%) to 97% (92.5-100%) (P < .001). Fewer subjects exhibited clinical
      signs of respiratory distress (10/17 vs 3/17, P = .03). HFNC was well tolerated
      and no adverse event was noted.  Altogether, 76% of healthcare givers declared
      preferring HFNC, as compared to conventional oxygen therapy. CONCLUSIONS: HFNC is
      possible in the ED, and it alleviated dyspnea and improved respiratory parameters
      in subjects with acute hypoxemic respiratory failure.

PMID- 22417845
TI  - Population-based laboratory assessment of the burden of community-onset
      bloodstream infection in Victoria, Canada.
AB  - Although community-onset bloodstream infection (BSI) is recognized as a major
      cause of morbidity and mortality, its epidemiology has not been well defined in
      non-selected populations. We conducted population-based laboratory surveillance
      in the Victoria area, Canada during 1998-2005 in order to determine the burden
      associated with community-onset BSI. A total of 2785 episodes were identified for
      an overall annual incidence of 101.2/100,000. Males and the very young and the
      elderly were at highest risk. Overall 1980 (71%) episodes resulted in hospital
      admission for a median length of stay of 8 days; the total days of acute
      hospitalization associated with community-onset BSI was 28 442 days or 1034
      days/100,000 population per year. The in-hospital case-fatality rate was 13%.
      Community-onset BSI is associated with a major burden of illness. These data
      support ongoing and future preventative and research efforts aimed at reducing
      the major impact of these infections.

PMID- 22417846
TI  - High extracellular matrix metalloproteinase inducer/CD147 expression is strongly
      and independently associated with poor prognosis in colorectal cancer.
AB  - As in most solid tumors, colorectal cancer prognosis strongly depends on the
      extent of local invasion and lymph node and distant metastases. Extracellular
      matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that
      activates matrix metalloproteinases, a group of enzymes that play an important
      role in tumor invasion and metastasis formation. This study investigates the
      EMMPRIN expression in a large cohort of patients with colorectal cancer.
      Immunohistochemical analysis of tissue microarrays from 285 patients shows that
      increased EMMPRIN protein expression does not correlate with clinicopathologic
      parameters and is an independent prognostic factor of poor survival, with mean
      survival times of 103 months in EMMPRIN negative/low versus 57 months in EMMPRIN
      intermediate/high patients (P < .001). This pronounced association of increased
      EMMPRIN levels and--on average--a 45% reduction in overall survival could help
      improve the risk stratification in patients with colorectal cancer; moreover, the
      lack of correlations with classical measures of cancer invasion/spreading may
      suggest the relevance of alternative EMMPRIN pathways beyond matrix
      metalloproteinase activation.

PMID- 22417847
TI  - Mutations in FGFR3 and PIK3CA, singly or combined with RAS and AKT1, are
      associated with AKT but not with MAPK pathway activation in urothelial bladder
      cancer.
AB  - Different members of the phosphoinositide 3 kinase--serine threonine protein
      kinase (PI3K-AKT) pathway are altered in bladder cancer. Fibroblast growth factor
      receptor 3 (FGFR3) mutations characterize the low-grade tumors, and RAS genes are
      mutated in approximately 13% of all bladder tumors. Interestingly, a percentage
      of bladder tumors have alterations in more than 1 PI3K-AKT or rat sarcoma viral
      oncogene homolog-RAF mitogen activated protein kinase (RAS-MAPK) pathway gene or
      their upstream regulators, but some combinations are mutually exclusive. We
      analyzed mutations in FGFR3, phosphoinositide 3 kinase catalytic alpha
      polypeptide (PIK3CA), v-akt murine thymoma viral oncogene homolog 1 (AKT1), v-Ki
      ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), v-Ha-ras Harvey rat
      sarcoma viral oncogene homolog (HRAS), and v-raf murine sarcoma viral oncogene
      homolog B1 (BRAF) in 88 urothelial cell carcinomas and the immunohistochemical
      expression of phospho-v-akt murine thymoma viral oncogene homolog (AKT) and
      mitogen-activated protein kinase 1 and 2 (pERK1/2) in 80 and 77 urothelial cell
      carcinomas, respectively. Approximately 43% and 20.5% of tumors presented 1 and 2
      mutated genes, respectively. FGFR3 mutations were more frequent alone, whereas
      PIK3CA mutations were associated with another mutated gene (FGFR3 and KRAS).
      Overall, mutated FGFR3 (FGFR3(mut)) and mutated FGFR3 (FGFR3(mut))-mutated PIK3CA
      (PIK3CA(mut)) genotypes were associated with low-grade bladder tumors and mutated
      PIK3CA (PIK3CA(mut))-mutated KRAS (KRAS(mut)) and mutated AKT1 (AKT1(mut)) were
      only present in high-grade tumors. There are no mutated FGFR3 (FGFR3(mut))
      mutated RAS (RAS(mut)) nor mutated PIK3CA (PIK3CA(mut))-mutated AKT1 (AKT1(mut))
      combinations. Fifty percent and 56% of tumors showed high levels of pAKT and
      pERK1/2, respectively. High levels of pAKT were associated with total mutations,
      FGFR3(mut), and PIK3CA(mut) tumors but not with tumor grade or stage. Wild-type
      tumors presented significantly higher pERK1/2 expression. Mutations in FGFR3 and
      FGFR3-PIK3CA but not single PIK3CA mutations characterize low-grade bladder
      tumors. Single FGFR3 or PIK3CA mutations and the different mutation combinations
      FGFR3-PIK3CA/AKT1 and PIK3CA-RAS can activate the AKT but not the MAPK pathway.
      Other genes different from FGFR3 may be related with the pERK activation in
      bladder tumors.

PMID- 22417848
TI  - Temporal trends in the treatment of severe traumatic hemorrhage.
AB  - BACKGROUND: This study examined the evolution of damage control resuscitation
      (DCR) and outcomes in severe traumatic hemorrhage (STH) at a large Canadian
      trauma center. METHODS: This was a retrospective cohort study of trauma patients
      admitted to a level 1 trauma center between 2005 and 2010, who received 10 or
      more units of packed red blood cells within 24 hours of admission. Demographic
      and clinical findings were compared between survivors and nonsurvivors. RESULTS:
      Forty-five patients were included. Twenty-five percent of patients were
      coagulopathic at admission. Early crystalloid use declined over the study period.
      The mean 24-hour fresh-frozen plasma:platelets:packed red blood cells ratio was
      1:1:2. Hemorrhage-related mortality was 69%. No pedestrians survived STH. A total
      of 1,032 blood product units were used in the first day for nonsurvivors.
      CONCLUSIONS: Principles of DCR crept into clinical practice even before the
      implementation of a formal STH protocol. DCR appeared to reduce the intensive
      care unit length of stay but not mortality. STH is associated with heavy use of
      blood bank resources and high mortality rates. Futility of resuscitative efforts
      may be predictable by mechanism and early physiological markers.

PMID- 22417849
TI  - Correlating Haller Index and cardiopulmonary disease in pectus excavatum.
AB  - BACKGROUND: The Haller Index (HI) has become standard for determining the
      severity of pectus excavatum. We compared patterns of cardiopulmonary dysfunction
      and their relationship with HI in patients with pectus excavatum. METHODS: We
      performed cardiopulmonary exercise testing and chest computed tomography scans on
      90 patients with pectus excavatum deformities at a regional pediatric hospital.
      RESULTS: The median HI was 4.9 in patients with combined dysfunction, 4.4 in
      patients with isolated pulmonary dysfunction, 3.6 in patients with isolated
      cardiac dysfunction, and 3.4 in patients with normal function. HI varied
      significantly by disease group (P < .009). HI was significantly lower in patients
      with normal forced vital capacity than with abnormal forced vital capacity (P =
      .001). However, HI was similar in patients with normal and abnormal oxygen pulse
      (P = .24) or peak oxygen consumption (P = .37). CONCLUSIONS: Fifty-nine percent
      of patients had cardiac and/or pulmonary limitation. A HI greater than 3.6 is
      associated with pulmonary dysfunction, but not cardiac dysfunction.

PMID- 22417850
TI  - Practice referral patterns and outcomes in patients with primary retroperitoneal
      sarcoma in British Columbia.
AB  - BACKGROUND: We examined practice referral patterns for primary retroperitoneal
      sarcoma (PRS) in British Columbia (BC) and associations between the timing of
      referral to tertiary care and patient outcomes. METHODS: Using ICD-10 coding, the
      Cancer Agency Information System was used to identify patients with PRS from 2000
      to 2009 who had been referred to tertiary care and had undergone a surgical
      resection. RESULTS: Eighty-two patients were included. Those referred before
      surgery were significantly more likely to receive a complete resection (P =
      .0002) and adjuvant radiation (P = .0000) compared with patients referred after
      surgery. Referral before surgery was associated with a significantly increased
      overall (P = .0619) and recurrence-free (P = .0400) survival; however, in the
      multivariate model this was not significant. CONCLUSIONS: Referral before surgery
      is associated with higher rates of complete resection and the use of adjuvant
      radiation; furthermore, it is associated with prolonged survival in the
      univariate but not in the multivariate model.

PMID- 22417851
TI  - Comment on: Blood clot obstruction of the jejunojejunostomy after laparoscopic
      gastric bypass.

PMID- 22417852
TI  - Updated position statement on sleeve gastrectomy as a bariatric procedure.

PMID- 22417853
TI  - Effects of a longitudinal magnetic field on spin injection and detection in
      InAs/GaAs quantum dot structures.
AB  - Effects of a longitudinal magnetic field on optical spin injection and detection
      in InAs/GaAs quantum dot (QD) structures are investigated by optical orientation
      spectroscopy. An increase in the optical and spin polarization of the QDs is
      observed with increasing magnetic field in the range 0-2 T, and is attributed to
      suppression of exciton spin depolarization within the QDs that is promoted by the
      hyperfine interaction and anisotropic electron-hole exchange interaction. This
      leads to a corresponding enhancement in spin detection efficiency of the QDs by a
      factor of up to 2.5. At higher magnetic fields, when these spin depolarization
      processes are quenched, the electron spin polarization in anisotropic QD
      structures (such as double QDs that are preferably aligned along a specific
      crystallographic axis) still exhibits a rather strong field dependence under non
      resonant excitation. In contrast, such a field dependence is practically absent
      in more 'isotropic' QD structures (e.g. single QDs). We attribute the observed
      effect to stronger electron spin relaxation in the spin injectors (i.e. wetting
      layer and GaAs barriers) of the lower-symmetry QD structures, which also explains
      the lower spin injection efficiency observed in these structures.

PMID- 22417854
TI  - Diagnostic role of inhibin alpha-subunit and inhibin/activin beta-subunit in
      adrenal cortical and medullary tumors in Egyptian patients.
AB  - Inhibin and activins are dimeric glycoproteins that are structurally and
      functionally related to transforming growth factor-beta and are composed of 1
      alpha-subunit and 1 of 2 beta-subunits (betaA or betaB). In recent years, there
      has been controversy about their role in adrenal tumors and their suitability as
      a diagnostic/predictive marker. Inhibin alpha and inhibin/activin beta protein
      expression was assessed on 47 adrenal tissue specimens by means of
      immunohistochemistry. Positive immunoreactivity of inhibin-alpha was seen in all
      studied hyperplastic adrenal glands, 90.9% of cortical adenomas, and 83.3% of
      adrenal cortical carcinomas. In contrast, the adrenomedullary neoplasms had a
      statistically significantly different behavior (P=0.001). We observed the
      negative expression of inhibin alpha in 85% and 80% of benign and malignant
      pheochromocytomas, respectively. As regards the immunoreactivity of
      inhibin/activin beta, 80% of adrenal hyperplasias, 81.8% of cortical adenomas,
      and 83.3% of adrenal cortical carcinomas showed positivity. Strong-to-weak
      positive staining of inhibin/activin beta was observed in 70% of benign
      pheochromocytomas, whereas malignant pheochromocytomas showed positive
      immunohistochemical staining in 40% of cases with weak intensity. The scoring of
      inhibin/activin beta immunoreactivity between adrenocortical and adrenomeullary
      neoplasia failed to reach the significant value (P=0.1). Our results demonstrate
      that inhibin alpha had a diagnostic role, differentiating between the
      adrenocortical and adrenomedullary neoplasms. Moreover, inhibin/activin beta
      might play a predictive role for malignant potential in pheochromocytoma. Further
      studies are warranted to determine whether they play a diagnostic/predictive role
      in adrenal tumors or are just surrogate markers for this group of neoplasia.

PMID- 22417855
TI  - Small cell carcinoma of the ileum that developed 10 years after total gastrectomy
      for gastric signet-ring cell carcinoma.

PMID- 22417856
TI  - Predictors of pathologic complete response after standard neoadjuvant
      chemotherapy in triple-negative breast carcinoma.
AB  - The objective of this study was to identify predictors of pathologic complete
      response and tumor volume reduction in triple-negative breast carcinomas.
      Consecutive cases of 101 triple-negative carcinomas within the last 3 years
      treated with standard neoadjuvant chemotherapy were identified. However, 56 cases
      with sufficient material available (for tissue microarray construction) in the
      pretherapy core biopsy tissue blocks formed the basis of this study. The
      pretherapy tumor core biopsy slides were examined for various morphologic
      features including tumor grade. The tumors were immunohistochemically examined
      for basal phenotype markers (CK5, CK14, CK17, epidermal growth factor receptor),
      cell adhesion marker E-cadherin, and proliferation marker Ki-67. The overall rate
      of pathologic complete response was 34% (19 of 56). Neither any morphologic
      feature nor any basal marker reactivity predicted for pathologic complete
      response or >50% tumor volume reduction. Ki-67 proliferation index also failed as
      a predictive marker. Reduced E-cadherin expression (defined as H score <=200) was
      initially seen in 47% of cases with pathologic complete response and in only 6%
      of cases that failed to achieve pathologic complete response (P=0.001); however,
      in additional 20 cases from a separate validation set, no such difference was
      identified. Basal marker reactivity in triple-negative breast carcinomas does not
      predict pathologic complete response after neoadjuvant chemotherapy. As vast
      majority of triple-negative tumors are highly proliferative, Ki-67 proliferation
      index appears to have negligible clinical value in predicting pathologic complete
      response. E-cadherin expression as a predictor of pathologic complete response in
      triple-negative tumors should be further assessed on larger number of cases.

PMID- 22417857
TI  - Simultaneous fluorescence immunophenotyping and Her-2/neu genotyping (FICTION) in
      breast carcinoma candidates to target therapy.
AB  - The study of proto-oncogene Her-2/neu using the fluorescence in situ
      hybridization (FISH) technique in routinely paraffin-embedded formalin-fixed
      tissue has become commonplace over the past decade and mandatory among invasive
      breast cancer expressing a score 2+ by immunohistochemical analysis of c-erbB2
      protein. The patient's eligibility for treatment with the biological drug
      trastuzumab/herceptin is based on the evidence of a Her-2/neu proto-oncogene
      amplification (ratio Her-2/neu/CEP-17>2.2). However, although the exclusion is
      declared in the absence of Her-2/neu gene amplification (ratio Her-2/neu/CEP-17
      <1.8) according to the American Society of Clinical Oncology/College of American
      Pathologists recommendations, there are borderline cases (1.8<ratio Her-2/neu/CEP
      17>2.2) that need to be investigated (eg, ductal carcinoma in situ with
      microinvasion, metastatic breast cancer). In such cases with Her-2/neu genetic
      heterogeneity it is difficult to count the nuclear signals in the areas of
      invasive tumor using fluorescence. The availability of a Fluorescence
      Immunophenotyping and Interphase Cytogenetics as a Tool for Investigation of
      Neoplasms technique, based on the simultaneous evaluation of immunostaining with
      anticytokeratins (CKAE1/AE3 and CK19), together with FISH for Her-2/neu gene
      status [it is therefore useful and of current applicability in breast cancer
      blocks (formalin-fixed and paraffin-embedded)], permits a more easy
      identification of even single neoplastic cells by immunofluorescence and then a
      better evaluation of Her-2/neu status gene by the FISH technique, as shown in our
      study.

PMID- 22417858
TI  - HER2 expression in breast cancer with nonamplified HER2 and gains of chromosome
      17 centromere.
AB  - Gains of chromosome 17 centromere (CEP17) may be accompanied by gains of
      chromosome 17q. To evaluate the effect of CEP17 gains (CEP17>3 copies per tumor
      nucleus) on the expression of the HER2 gene, which is located on chromosome 17q12
      21.32, we analyzed HER2 amplification and expression in breast carcinomas with
      and without CEP17 gains. We isolated tumor nuclei from frozen tissues of 37
      breast carcinomas for analysis of the HER2 gene and CEP17 by fluorescence in situ
      hybridization. HER2 expression was detected by immunohistochemistry (IHC)
      performed on formalin-fixed, paraffin-embedded sections of the corresponding
      tumors. Tumors with amplified HER2 as determined by both HER2 copy number and
      HER2/CEP17 ratio were detected in 29.7% (11/37). CEP17 gains were significantly
      associated with HER2 amplification (P=0.005) but not associated with estrogen
      receptor status, tumor grade, and lymph node status (P>0.05). In contrast, HER2
      amplification was significantly associated with estrogen receptor negativity
      (P=0.020) but not with tumor grade and lymph node status (P>0.05). IHC analysis
      was performed in 7 HER2-amplified tumors and all of these were IHC 3+, which were
      used as positive controls. Among HER2-non-amplified tumors with CEP17 gains, only
      1 tumor (1/8, 12.5%) was IHC 3+. However, none of the HER2-non-amplified tumors
      without CEP17 gains was IHC 3+. In HER2-non-amplified tumors, there was no
      significant association between HER2 protein expression as detected by IHC and
      CEP17 or HER2 copy number (P=0.999, P=0.785, respectively). These findings
      indicate that in the absence of HER2 amplification, CEP17 gains do not have a
      significant effect on HER2 protein expression.

PMID- 22417859
TI  - CD10+ and CK7/RON- immunophenotype distinguishes renal cell carcinoma,
      conventional type with eosinophilic morphology from its mimickers.
AB  - BACKGROUND: The distinction between renal cell carcinoma conventional (clear
      cell) type with eosinophilic morphology (ccRCC), chromophobe renal cell carcinoma
      eosinophilic variant (chRCC), and renal oncocytoma (RO) is a common diagnostic
      dilemma. We aimed to identify an immunohistochemical panel to discriminate ccRCC
      from its morphologic mimics. MATERIALS AND METHODS: Fifty-three renal neoplasms
      (19 ccRCC, 18 chRCC, and 16 RO) were selected. Immunohistochemical stains for
      CD10, cytokeratin 7 (CK7), c-Kit, E-cadherin, N-cadherin, kidney-specific
      cadherin (Ksp-cadherin), and Recepteur d'origine nantais (RON) were performed.
      RESULTS: Ten (53%) of 19 ccRCC were positive for CD10, 11 (58%) for E-cadherin, 8
      (42%) for N-cadherin, 5 (26%) for Ksp-cadherin, 9 (47%) for RON, 6 (32%) for CK7,
      and 5 (26%) for c-Kit. In chRCC/RO group, 5 of 34 (15%) were positive for CD10,
      32 (94%) for E-cadherin, 2 (6%) for N-cadherin, 1 (3%) for Ksp-cadherin, 22 (65%)
      for RON, 14 (41%) for CK7, and 25 (25/32, 76%) for c-kit. Univariately, negative
      c-Kit [odds ratio (OR)=8.75, P=0.001, area under the receiver operating
      characteristic curve (AUC)=0.747], negative E-cadherin (OR=11.64, P=0.005,
      AUC=0.681), positive N-cadherin (OR=11.64, P=0.005, AUC=0.681), positive Ksp
      cadherin (OR=11.79, P=0.031, AUC=0.617), and positive CD10 (OR=6.44, P=0.005,
      AUC=0.690) detects ccRCC versus chRCC/RO. Multivariate analysis showed
      significant association between CD10 positivity and ccRCC (OR=16.90, P=0.007) and
      between RON negativity and ccRCC (OR=7.17, P=0.047) when CK7 is negative.
      CONCLUSIONS: The best single predictors for ccRCC are negative c-Kit, negative E
      cadherin, positive N-cadherin, positive Ksp-cadherin, and positive CD10. However,
      considering the studied markers, a combination of positive CD10 and negative CK7
      and RON is considered the best immunohistochemical panel in distinguishing ccRCC
      from chRCC/RO.

PMID- 22417860
TI  - Increased angiogenesis-associated poor outcome in acute lymphoblastic leukemia: a
      single center study.
AB  - Angiogenesis in solid tumors is important for tumor growth, invasion, and
      metastasis. However, angiogenesis plays also an important role in hematological
      malignancies. We have analyzed the expression of vascular endothelial growth
      factor (VEGF) in the leukemic blast cells and microvessel density (MVD) in the
      bone marrow biopsy samples of the patients with acute lymphoblastic leukemia
      (ALL). Bone marrow MVD of the patients with ALL was significantly higher compared
      with normal controls and complete remission (P<0.001), but slightly lower than in
      patients with relapsed ALL (P>0.05). The bone marrow blast VEGF expression was
      significantly higher in newly diagnosed ALL patients, with predominant strong
      VEGF expression as compared with complete remission patients (who had negative or
      weak VEGF expression) (P<0.05), whereas initial values were slightly lower than
      in relapsed patients. There was a strong positive correlation between VEGF
      expression and MVD at presentation of ALL. Stronger expression of VEGF on blast
      cells indicates shorter overall survival in ALL. Furthermore, initial values of
      MVD had positive correlation with overall survival and leukemia-free survival
      (P=0.024 and P=0.017, respectively). Our data suggest that increased angiogenesis
      (confirmed by immunohistochemical expression of VEGF in leukemic blasts), and MVD
      may play an important role in the pathophysiology of ALL with prognostic
      implications. Thus, targeting VEGF pathway may bring the new approach for ALL
      treatment-using antiangiogenic drugs and tyrosine kinase inhibitors in
      combination with standard chemotherapy regimens.

PMID- 22417861
TI  - Anti-glutamate receptor 2 as a new potential diagnostic probe for prostatic
      adenocarcinoma:  a pilot immunohistochemical study.
AB  - Diagnoses of prostatic carcinoma (PC) have increased with widespread screening.
      While the use of alpha-methylacyl coA racemase and high molecular weight
      cytokeratins have aided in distinguishing benign mimics from malignancy, their
      sensitivity and specificity are limited. We studied 6C4, a monoclonal antibody to
      glutamate receptor 2, an excitatory amino acid receptor subunit distributed
      throughout the central nervous system, on benign prostatic epithelium, high-grade
      prostatic intraepithelial neoplasia, and PC. Ten cases with post-atrophic or
      adenosis-like prostate glands were also stained with prostatic intraepithelial
      neoplasia 4, an immunostain cocktail against alpha-methylacyl coA racemase, p63,
      and high molecular weight cytokeratin, in parallel with 6C4. Immunoreactivity for
      6C4 was graded as negative (0% to 10%), +1 (11%% to 50%), and +2 (>50%).
      Malignant epithelium was classified by Gleason patterns. Gleason patterns 4 and 5
      were subdivided into cribriform or noncribriform type. Its utility in
      distinguishing postatrophic or adenosis-like glands from prostate cancer, both of
      which show absence of basal cells on prostatic intraepithelial neoplasia 4
      immunostain, was also investigated. Our results revealed a statistically
      significant difference in staining of benign secretory prostatic epithelium, high
      grade prostatic intraepithelial neoplasia, and low Gleason pattern carcinomas.
      The results also showed 6C4 is a sensitive marker in separating basal cell
      negative postatrophic or adenosis-like glands from prostate carcinoma. In
      addition, there was a statistically significant difference between staining of
      cribriform versus noncribriform Gleason pattern 4 and 5 carcinomas. A limited
      number of lymph node metastases from cribriform and noncribriform carcinomas were
      studied, and they stained the same as the primary tumor in the majority of cases.
      In conclusion, our preliminary data demonstrated potential utility of 6C4 in the
      pathologic evaluation of PC.

PMID- 22417862
TI  - Empathy and the application of the 'unbearable suffering' criterion in Dutch
      euthanasia practice.
AB  - A pivotal due care criterion for lawful euthanasia in the Netherlands is that
      doctors must be convinced that a patient requesting for euthanasia, suffers
      unbearably. Our study aims to find out how doctors judge if a patient suffers
      unbearably. How do doctors bridge the gap from 3rd person assessment to 1st
      person experience? We performed a qualitative interview study among 15
      physicians, mainly general practitioners, who participated earlier in a related
      quantitative survey on the way doctors apply the suffering criterion. Results
      show that doctors follow different 'cognitive routes' when assessing a patients
      suffering in the context of a euthanasia request. Sometimes doctors do this
      imagining how she herself would experience the situation of the patient ('imagine
      self'). Doctors may also try to adopt the perspective of the patient and imagine
      what the situation is like for this particular patient ('imagine other'). Besides
      this we found that the (outcome of the) assessment is influenced by a doctor's
      private norms, values and emotions considering (the performance of) euthanasia.
      We conclude by arguing why doctors should be aware of both the 'cognitive route'
      followed as well as the influence of their own personal norms on the assessment
      of suffering in the context of euthanasia requests.

PMID- 22417863
TI  - Is pharmaceutical policy evidence-informed? A case of the deregulation process of
      nicotine replacement therapy products in Finland.
AB  - OBJECTIVE: This qualitative study aims to identify the key dimensions of the
      political argumentation in the debate leading up to the deregulation of nicotine
      replacement therapy products (NRT) in Finland in 2006. The deregulation was
      introduced by the Amendment of larger package of changes in medical legislation
      prepared in 2005. METHODS: All publicly available documents of the legislative
      process introducing NRT deregulation and interviews of 12 Members of Finnish
      Parliament conducted in spring 2006 were analyzed by inductive content analysis.
      RESULTS: NRT deregulation was introduced to decision-makers as a safe
      intervention to increase smoking cessation and thus provide public health
      benefits. However, a whole variety of other features were brought into debate:
      NRT characteristics, principle change in prevailing medical legislation, use of
      evidence and the political process. Finally, the expected public health benefits
      of the decision were not directly informed by any evidence. CONCLUSIONS: This
      study provides an example of the use of public health benefits as justification
      for decision-making. However, the decision can include other aspects, less
      brought up in its preparation stage. Our study addresses the need for
      policymakers to critically evaluate the evidence, its suitability in decision
      making context and raise awareness of the principles of evidence-informed policy
      making.

PMID- 22417864
TI  - Clonality in gynecologic neoplasms: is it time to reevaluate clonality studies in
      gynecologic neoplasms? Is it possible to confirm multicentricity with clonality
      studies?
AB  - This article reviews issues with clonality applied to gynecologic neoplasms. It
      is our opinion that the current interpretation of clonality studies in
      gynecologic neoplasms needs to be reevaluated because multicentricity, probably a
      common mechanism of tumor development in gynecology, cannot be confirmed with
      clonality.

PMID- 22417865
TI  - Selective spatial processing deficits in an at-risk subgroup of the fragile X
      premutation.
AB  - Until a decade ago, it was assumed that males with the fragile X premutation were
      unaffected by any cognitive phenotype. Here we examined the extent to which CGG
      repeat toxicity extends to visuospatial functioning in male fragile X premutation
      carriers who are asymptomatic for a late-onset neurodegenerative disorder,
      fragile X-associated tremor/ataxia syndrome (FXTAS). Thirty-three premutation
      males aged 20-68 years [divided into two groups: 16 low-repeat carriers (CGG >=
      55 <= 100) and 17 high-repeat carriers (CGG>100)] with a family history of
      fragile X syndrome and 62 non-affected adult males with normal FMR1 alleles were
      recruited. Subjects underwent neuropsychological tests of visuospatial and visual
      working memory functioning and visuoperceptual processing. On measures of
      visuospatial processing, the high-repeat carriers performed significantly worse
      than the normal allele group when age and IQ were covaried out. With increasing
      age and only in carriers of a larger (>100 repeats) premutation allele was there
      a greater decrement in visuospatial working memory functioning. Performance on
      spatial and perceptual judgement tasks failed to show similar specificity in
      males within the upper premutation range. We conclude that identification of
      selective visuospatial impairments in carriers of a larger premutation allele
      indicates greater CGG repeat toxicity in specific neural regions. Longitudinal
      follow-up studies will be needed to determine whether subtle decline in
      visuospatial functioning is associated with the later onset of motor symptoms of
      FXTAS.

PMID- 22417867
TI  - Aromatic compounds from endophytic fungus Colletotrichum sp. L10 of Cephalotaxus
      hainanensis Li.
AB  - Six aromatic compounds were isolated from the endophytic fungus Colletotrichum
      sp. of Cephalotaxus hainanensis Li [Cephalotaxus mannii Hook. f.]. Their
      structures were determined on the basis of chemical and spectroscopic methods.
      The compound 2 was the enantiomer of compound 1. The compound 4 was the epimeride
      of the compound 3. The compounds 1, 2, 4 and 5 were evaluated for cytostatic
      activity against HL-60 and PC-3 cells.

PMID- 22417868
TI  - Prediction of the mechanical response of the femur with uncertain elastic
      properties.
AB  - A mandatory requirement for any reliable prediction of the mechanical response of
      bones, based on quantitative computer tomography, is an accurate relationship
      between material properties (usually Young's modulus E) and bone density rho.
      Many such E-rho relationships are available based on different experiments on
      femur specimens with a large spread due to uncertainties. The first goal of this
      study is to pool and analyze the relevant available experimental data and develop
      a stochasticE-rho relationship. This analysis highlights that there is no
      experimental data available to cover the entire density range of the human femur
      and that some "popular" E-rho relationships are based on data that contains
      extreme scatter, while others are based on a very limited amount of information.
      The second goal is to use the newly developed stochastic E-rho relationship in
      high-order finite element analyses (FEAs) for the computation of strains and
      displacements in two human proximal femurs, mimicking in vitro experiments. When
      compared with the experimental observations, the FEA predictions using the median
      of the stochastic E-rho relationship follow the underlying distribution of the
      stochastic E-rho relationship. Thus, most deviations of the FEA predictions from
      experimental observations can possibly be explained by uncertain elastic
      properties of the femur.

PMID- 22417869
TI  - Flow resistance analysis of extracranial-to-intracranial (EC-IC) vein bypass.
AB  - Although brain bypass surgery has often been selected to treat internal carotid
      arteries (ICA) which are restricted by aneurysm or artery stenosis, its
      effectiveness has not been quantitatively evaluated. The purpose of this study is
      to propose an innovative approach for the evaluation of brain extracranial-to
      intracranial (EC-IC) vein bypass surgery, based on the analysis of flow
      resistance in vein bypasses and within their contralateral carotid arteries
      through the use of computational fluid dynamics (CFD). Seven patients who
      underwent vein bypass surgery were examined with the use of high-resolution;
      computed tomography angiogram (CTA). The reconstructed three-dimensional (3D)
      geometries were segmented to create CFD calculation domains. Colour Doppler
      ultrasound (CDU) was used to measure blood flow velocities at the common carotid
      arteries (CCA), in order to determine inflow conditions. Based on the pipe flow
      theory, pressure drop was expressed as Am2+Bm where A and B represent flow
      resistance coefficients and m represents blood mass flow rate. The CFD results
      revealed that for a healthy ICA, the average values of A and B were 0.013088
      Pa/(ml/min)2 and 3.105 Pa/(ml/min), respectively. For the vein bypass, an average
      value of A was 0.0143 Pa/(ml/min)2 and B 3.402 Pa/(ml/min), which was
      approximately that of a healthy ICA. However, in the case of a bypass utilising a
      venous conduit possessing a large-sized valve or existing size alteration, the
      flow resistance in that bypass would be higher than those found in the healthy
      ICA. An imbalance of flow resistances may impose conditions that could predispose
      hemodynamic failure or distal aneurysm development.

PMID- 22417866
TI  - Adipose tissue stem cells: the great WAT hope.
AB  - The past decade has witnessed an explosion in research into adipose tissue stem
      cells (ASCs), facilitated by their ease of isolation from white adipose tissue
      (WAT) and fueled by their therapeutic potential. Recent developments have
      extended ASC multipotency to include endodermal and ectodermal cell types, as
      well as the generation of induced pluripotent stem cells. This expanding
      multipotency has been paralleled by burgeoning translational applications,
      ranging from tissue engineering to anti-cancer therapy, that are currently
      subject to clinical trials. However, this promise is tempered by potential
      pitfalls, such as tumorigenicity, and is further undermined by lingering
      uncertainties regarding the precise identity of ASCs. Confronting these issues
      will be essential if we are to bypass the pitfalls and develop the promises of
      ASCs.

PMID- 22417870
TI  - ER and HER2 expression are positively correlated in HER2 non-overexpressing
      breast cancer.
AB  - INTRODUCTION: Estrogen receptor-alpha (ER) and human epidermal growth factor
      receptor 2 (HER2) positivity are inversely correlated by standard criteria.
      However, we investigated the quantitative relation between ER and HER2 expression
      at both RNA and protein levels in HER2+ve and HER2-ve breast carcinomas. METHODS:
      ER and HER2 levels were assessed with immunohistochemistry (IHC) and (for HER2)
      fluorescent in situ hybridization (FISH) and by quantitative reverse
      transcription-polymerase chain reaction (q-RT-PCR) in formalin-fixed primary
      breast cancers from 448 patients in the National Cancer Research Institute (NCRI)
      Adjuvant Breast Cancer Trial (ABC) tamoxifen-only arm. Relations at the RNA level
      were assessed in 1,139 TransATAC tumors. RESULTS: ER and HER2 RNA levels were
      negatively correlated as expected in HER2+ve (IHC 3+ and/or FISH-amplified)
      tumors (r = -0.45; P = 0.0028). However, in HER2-ve tumors (ER+ve and ER-ve
      combined), a significant positive correlation was found (r = 0.43; P < 0.0001),
      HER2 RNA levels being 1.74-fold higher in ER+ve versus ER-ve tumors. This
      correlation was maintained in the ER+veHER2-ve subgroup (r = 0.24; P = 0.0023)
      and confirmed in this subgroup in 1,139 TransATAC tumours (r = 0.25; P < 0.0001).
      The positive relation extended to IHC-detected ER in ABC: mean +/- 95% confidence
      interval (CI) H-scores were 90 +/- 19 and 134 +/- 19 for 0 and 1+ HER2 IHC
      categories, respectively (P = 0.0013). A trend toward lower relapse-free survival
      (RFS) was observed in patients with the lowest levels of ER and HER2 RNA levels
      within the ER+veHER2-ve subgroup both for ABC and TransATAC cohorts. CONCLUSIONS:
      ER and HER2 expression is positively correlated in HER2-ve tumors. The
      distinction between HER2+ve and HER2-ve is greater in ER-ve than in ER+ve tumors.
      These findings are important to consider in clinical trials of anti-HER2 and anti
      endocrine therapy in HER2-ve disease. TRIAL REGISTRATION: Clinical trial
      identifier: ISRCTN31514446.

PMID- 22417871
TI  - Identification of genes and proteins specifically regulated by costimulation of
      mast cell Fcepsilon Receptor I and chemokine receptor 1.
AB  - Mast cell function is a critical component of allergic reactions. Mast cell
      responses mediated by the high-affinity immunoglobulin E receptor FcepsilonRI can
      be enhanced by co-activation of additional receptors such as CC chemokine
      receptor 1 (CCR1). To examine the downstream effects of FcepsilonRI-CCR1
      costimulation, rat basophilic leukemia cells stably transfected with CCR1 (RBL
      CCR1 cells) were sensitized and activated with antigen and/or the CCR1 ligand CC
      chemokine ligand (CCL) 3. Gene and protein expression were determined at 3h and
      24h post-activation, respectively, using GeneChip and Luminex bead assays. Gene
      microarray analysis demonstrated that 32 genes were differentially regulated in
      response to costimulation, as opposed to stimulation with antigen or CCL3 alone.
      The genes most significantly up-regulated by FcepsilonRI-CCR1 costimulation were
      Ccl7, Rgs1, Emp1 and RT1-S3. CCL7 protein was also expressed at higher levels 24h
      after dual receptor activation, although RGS1, EMP1 and RT1-S3 were not. Of the
      panel of chemokines and cytokines tested, only CCL2, CCL7 and interleukin (IL)-6
      were expressed at higher levels following costimulation. IL-6 expression was seen
      only after FcepsilonRI-CCR1 costimulation, although the amount expressed was very
      low. CCL7, CCL2 and IL-6 might play roles in mast cell regulation of late-phase
      allergic responses.

PMID- 22417872
TI  - Small-size biofuel cell on paper.
AB  - In this work, we demonstrated a novel paper-based mediator-less and compartment
      less biofuel cell (BFC) with small size (1.5 cm * 1.5 cm). Ionic liquid
      functionalized carbon nanotubes (CNTs-IL) nanocomposite was used as support for
      both stably confining the anodic biocatalyst (i.e., NAD(+)-dependent glucose
      dehydrogenase, GDH) for glucose electrooxidation and for facilitating direct
      electrochemistry of the cathodic biocatalyst (i.e., bilirubin oxidase, BOD) for
      O(2) electroreduction. Such BFC provided a simple approach to fabricate low-cost
      and portable power devices on small-size paper, which can harvest energy from a
      wide range of commercial beverages containing glucose (e.g., Nescafe instant
      coffee, Maidong vitamin water, Watermelon fresh juice, and Minute Maid grape
      juice). These made the low-cost paper-based biodevice potential for broad energy
      applications.

PMID- 22417873
TI  - A G-quadruplex based label-free fluorescent biosensor for lead ion.
AB  - Many Pb(2+) biosensors based on Pb(2+)-specific RNA-cleaving DNAzyme have been
      developed in the past years. However, many of them have limited practical use
      because of high cost (e.g., enzymes), complicated processing and the use of
      unstable molecules (e.g., RNA). In this study, a novel label-free fluorescent
      biosensor for Pb(2+) was proposed based on Pb(2+)-induced allosteric G-quadruplex
      (PS2.M). In the presence of K(+), N-methyl mesoporphyrin IX (NMM) could bind to
      K(+)-stabilized G-quadruplexes, giving rise to high fluorescence. On addition of
      Pb(2+), Pb(2+) competitively binded to K(+)-stabilized G-quadruplexes to form
      more compact DNA folds. The Pb(2+)-stabilized G-quadruplexes did not bind to NMM,
      which resulted in fluorescence decrease. This allowed us to utilize PS2.M for
      quantitative analysis of Pb(2+) using the NMM-G-quadruplex system by convenient
      "mix-and-detect" protocol. The fluorescence emission ratio (F(0)/F) showed a good
      linear response toward Pb(2+) over the range from 5.0 nM to 1.0 MUM with a limit
      of detection of 1.0 nM. This proposed biosensor was simple and cost efficiency in
      design and in operation with high sensitivity and selectivity. We validated the
      practicality of this biosensor for the determination of Pb(2+) in lake water
      samples.

PMID- 22417874
TI  - TiO2/MWNTs nanocomposites-based electrochemical strategy for label-free assay of
      casein kinase II activity and inhibition.
AB  - In this paper, a novel label-free electrochemical strategy has been developed for
      assay of casein kinase II (CK2) activity and inhibition using TiO(2)/MWNTs
      nanocomposites. This detection system takes advantage of specific binding of the
      phosphate groups with TiO(2) nanoparticles and fast electron transfer rate of
      MWNTs. In this strategy, the synthesized TiO(2)/MWNTs nanocomposite was firstly
      deposited on the surface of a glassy carbon electrode (GCE). The presence of
      MWNTs not only increased the surface area of the electrode but also promoted
      electron-transfer reaction. In the presence of CK2, the kinase reaction resulted
      in the phosphorylation of peptide substrates. The phosphorylated peptides were
      subsequently captured to the surface of GCE modified with TiO(2)/MWNTs
      nanocomposite through specific binding of the phosphate groups with TiO(2)
      nanoparticles. Then the access of redox probe [Fe(CN)(6)](3-/4-) to electrode
      surface was blocked. As a result, the decrease peak currents were related to the
      concentrations of the CK2, providing a sensing mechanism for monitoring peptides
      phosphorylation. The electrochemical strategy can be employed to assay CK2
      activity with a low detection limit of 0.07 U/mL. The linear range of the assay
      for CK2 was 0-0.5 U/mL. Furthermore, the interferences experiments of PKA and
      inhibition of CK2 have been also studied by using this strategy.

PMID- 22417875
TI  - Amperometric biosensor based on diamond paste for the enantioanalysis of L
      lysine.
AB  - An amperometric biosensor was proposed for the enantioanalysis of L-lysine. The
      biosensor is based on the impregnation of L-lysine oxidase in diamond paste. The
      potential used for the determination of l-lysine was 650 mV. The biosensor
      exhibited a linear concentration range between 1 and 100 nmol/L with a limit of
      detection of 4 pmol/L. The selectivity of the biosensor is high over other amino
      acids, such as L-serine, L-leucine, L-aspartic acid, L-glutamic acid, histamine,
      glycine. The proposed biosensor can be applied for the determination of L-lysine
      in serum samples and pharmaceutical compounds.

PMID- 22417876
TI  - What are the most sensitive and specific sign and symptom combinations for
      influenza in patients hospitalized with acute respiratory illness? Results from
      western Kenya, January 2007-July 2010.
AB  - Influenza causes severe illness and deaths, and global surveillance systems use
      different clinical case definitions to identify patients for diagnostic testing.
      We used data collected during January 2007-July 2010 at hospital-based influenza
      surveillance sites in western Kenya to calculate sensitivity, specificity,
      positive predictive value, and negative predictive value for eight clinical
      sign/symptom combinations in hospitalized patients with acute respiratory
      illnesses, including severe acute respiratory illness (SARI) (persons aged 2-59
      months: cough or difficulty breathing with an elevated respiratory rate or a
      danger sign; persons aged >=5 years: temperature >=38  degrees C, difficulty
      breathing, and cough or sore throat) and influenza-like illness (ILI) (all ages:
      temperature >=38  degrees C and cough or sore throat). Overall, 4800 persons aged
      >=2 months were tested for influenza; 416 (9%) had laboratory-confirmed influenza
      infections. The symptom combination of cough with fever (subjective or measured
      >=38  degrees C) had high sensitivity [87.0%, 95% confidence interval (CI) 83.3
      88.9], and ILI had high specificity (70.0%, 95% CI 68.6-71.3). The case
      definition combining cough and any fever is a simple, sensitive case definition
      for influenza in hospitalized persons of all age groups, whereas the ILI case
      definition is the most specific. The SARI case definition did not maximize
      sensitivity or specificity.

PMID- 22417878
TI  - Quantification of proteins on gold nanoparticles by combining MALDI-TOF MS and
      proteolysis.
AB  - Protein-coated nanoparticles have been used in many studies, including those
      related to drug delivery, disease diagnosis, therapeutics, and bioassays. The
      number and density of proteins on the particles' surface are important parameters
      that need to be calculable in most applications. While quantification methods for
      two-dimensional surface-bound proteins are commonly found, only a few methods for
      the quantification of proteins on three-dimensional surfaces such as
      nanoparticles have been reported. In this paper, we report on a new method of
      quantifying proteins on nanoparticles using matrix assisted laser
      desorption/ionization time of flight (MALDI-TOF) mass spectrometry (MS). In this
      method, the nanoparticle-bound proteins are digested by trypsin and the resulting
      peptide fragments are analyzed by MALDI-TOF MS after the addition of an isotope
      labeled internal standard (IS) which has the same sequence as a reference peptide
      of the surface-bound protein. Comparing the mass intensities between the
      reference peptide and the IS allows the absolute quantification of proteins on
      nanoparticles, because they have the same molecular milieu. As a model system,
      gold nanoparticles were examined using bovine serum albumin (BSA) as a coating
      protein. We believe that our strategy will be a useful tool that can provide
      researchers with quantitative information about the proteins on surfaces of three
      dimensional materials.

PMID- 22417879
TI  - Gene expression profiling of oral epithelium during tooth development.
AB  - OBJECTIVE: Tooth development is regulated by the complex interplay of various
      regulatory molecules. To identify new regulatory genes released from the dental
      epithelium, gene expression profiling of dental epithelium was analysed. DESIGN:
      ICR mouse dental epithelia were isolated from the initiation (E10.5) and bell
      (E16.5) stages, and microarray analysis was performed using Affymetrix
      GeneChip((r)). Microarray data were validated using reverse transcriptase
      polymerase chain reaction (RT-PCR), and gene ontology and signalling network were
      analysed. RESULTS: Detection signals more than 300 and changes more than two
      folds were considered as positive signals and were further analysed. Expressions
      of 193 genes in the E10.5 epithelium and 582 genes in the E16.5 epithelium were
      significantly increased. Validation of the selected genes using RT-PCR showed a
      well correlation with microarray data. Subsequent signalling network analysis
      revealed that at E10.5 and 16.5, nine genes such as histones, signalling
      molecules and transcription factors were closely related with neighbouring
      molecules. Moreover, gene ontology analysis showed that seven growth
      factors/receptors or secreted proteins were highly expressed at E10.5, including
      the platelet-derived growth factor, C polypeptide (Pdgfc), insulin-like growth
      factor binding protein 2 (Igfbp2) and Igfbp5. At E16.5, nine growth
      factors/receptors or secreted proteins, including Igfbp3, Igfbp10/Cyr61 and
      heparin-binding EGF-like growth factor (Hbegf) were highly expressed.
      CONCLUSIONS: These data suggest that the regulatory genes newly identified in
      this study may play significant roles in tooth development.

PMID- 22417880
TI  - Distribution of periodontopathic bacterial species in dogs and their owners.
AB  - OBJECTIVE: Presently, a large number of individuals consider their companion
      animals as family members and have close contact with them in daily life. The
      purpose of the present study was to analyze the distribution of periodontopathic
      bacterial species in oral specimens taken from dogs and their owners. DESIGN:
      Dental plaque specimens were collected from 66 dogs and 81 members of 64 families
      who came to an animal clinic or dog training school in Okayama, Japan, in 2011.
      Bacterial DNA was extracted from each specimen and PCR analyses using primers
      specific for 11 periodontopathic species, Porphyromonas gingivalis, Porphyromonas
      gulae, Treponema denticola, Tannerella forsythia, Capnocytophaga ochracea,
      Capnocytophaga sputigena, Prevotella intermedia, Prevotella nigrescens,
      Aggregatibacter actinomycetemcomitans, Campylobacter rectus, and Eikenella
      corrodens were performed. RESULTS: P. gulae (71.2%), T. forsythia (77.3%), and C.
      rectus (66.7%) were frequently found in the dogs, whereas the detection rates of
      those species in humans were less frequent at 16.0%, 30.9%, and 21.0%,
      respectively. P. gulae was identified in 13 human subjects and each of their dogs
      was also positive for the species. Furthermore, E. corrodens and T. denticola in
      specimens obtained from dogs were correlated with their presence in specimens
      from owners who had close contact with them. CONCLUSIONS: These results suggest
      that several periodontopathic species could be transmitted between humans and
      their companion dogs, though the distribution of periodontopathic species in both
      is generally different.

PMID- 22417877
TI  - Treating ethnic minority adults with anxiety disorders: current status and future
      recommendations.
AB  - The past three decades have witnessed an increase in the number of empirical
      investigations examining the phenomenology of anxiety and related conditions.
      There has also been an increase in efforts to understand differences that may
      exist between ethnic groups in the expression of the anxiety disorders. In
      addition, there is now substantial evidence that a variety of treatment
      approaches (most notably behavioral and cognitive behavioral) are efficacious in
      remediating anxiety. However, there continues to be comparatively few treatment
      outcome studies investigating the efficacy of anxiety treatments among minority
      populations. In this paper, we review the extant treatment outcome research for
      African American, Hispanic/Latino[a] American, Asian American, and Native
      Americans suffering with one of the anxiety disorders. We discuss some of the
      specific problems with the research in this area, and then provide specific
      recommendations for conducting treatment outcome research with minority
      populations in the future.

PMID- 22417881
TI  - Effects of soil water content and organic matter addition on the speciation and
      bioavailability of heavy metals.
AB  - The mobility and bioavailability of cadmium, copper, lead and zinc were evaluated
      in three soils amended with different organic materials for two moisture regimes.
      Agricultural and reclamation activities impose fresh inputs of organic matter on
      soil while intensive irrigation and rainstorm increase soil waterlogging
      incidence. Moreover, scarcity of irrigation water has prompted the use of
      greywater, which contain variable concentrations of organic compounds such as
      anionic surfactants. Soils added with hay, maize straw or peat at 1% w/w were
      irrigated, at field capacity (FC) or saturated (S), with an aqueous solution of
      the anionic surfactant Aerosol 22 (A22), corresponding to an addition of 200
      mgC/kgsoil/day. Soil solution was extracted after one month and analysed for
      total soluble metals, dissolved soil organic matter and UV absorbance at 254 nm.
      Speciation analyses were performed with WHAM VI for Cd, Cu, Pb, and Zn. For
      selected scenarios, metal uptake by barley was determined. Metal mobility
      increased for all treatments and soils (Pb>Cu>Cd>=Zn) compared to control assays.
      The increase was significantly correlated (p<0.05) with soil organic matter
      solubilisation for Cd (R=0.68), Cu (R=0.73) and Zn (R=0.86). Otherwise, Pb
      release was related to aluminium solubilisation (R=0.75), which suggests that Pb
      was originally co-precipitated with Al-DOC complexes in the solid phase. The
      effect of A22 in metal bioavailability, determined as free ion activities (FIA),
      was mainly controlled by soil moisture regime. For soil 3, metal bioavailability
      was up to 20 times lower for soil amended with hay, peat or maize compared to
      soil treated only with A22. When soil was treated with A22 at FC barley yield
      significantly decreased (p<0.05) for the increase of Pb (R=0.71) and Zn (R=0.79)
      concentrations in shoot, while for saturated conditions such uptake was up to 3
      times lower. Overall, metal bioavailability was controlled by solubilisation of
      soil organic matter and formation of metal-organo complexes.

PMID- 22417882
TI  - Natural attenuation of contaminated marine sediments from an old floating dock
      Part II: changes of sediment microbial community structure and its relationship
      with environmental variables.
AB  - Changes of microbial community structure and its relationship with various
      environmental variables in surface marine sediments were examined for a one-year
      period after the removal of an old floating dock in Hong Kong SAR, South China.
      Temporal variations in the microbial community structure were clearly revealed by
      principal component analysis (PCA) of the microbial ester-linked fatty acid
      methyl ester (EL-FAME) profiles. The most obvious shift in microbial community
      structure was detected 6 months after the removal of the dock, although no
      significant decline in the levels of pollutants could be detected. As determined
      by EL-FAME profiles, the microbial diversity recovered and the predominance of
      gram-negative bacteria was gradually replaced by gram-positive bacteria and fungi
      in the impacted stations. With redundancy analysis (RDA), the concentration of
      total polycyclic aromatic hydrocarbons (PAHs) was found to be the second
      important determinant of microbial community structure, next to Time. The
      relative abundance of 18:1omega9c and hydroxyl fatty acids enriched in the PAH
      hot spots, whereas 16:1omega9 and 18:1omega9t were negatively correlated to total
      PAH concentration. The significant relationships observed between microbial EL
      FAME profiles and pollutants, exampled by PAHs in the present study, suggested
      the potential of microbial community analysis in the assessment of the natural
      attenuation process in contaminated environments.

PMID- 22417883
TI  - Role of riverine colloids in macronutrient and metal partitioning and transport,
      along an upland-lowland land-use continuum, under low-flow conditions.
AB  - An assessment is made of the role of riverine colloids in macronutrient
      (nitrogen, phosphorus and carbon), metal and trace element partitioning and
      transport, for five rivers in the Ribble and Wyre catchments in north-western
      England, under baseflow/near-baseflow conditions. Cross-flow ultrafiltration was
      used to separate colloidal (<0.45 um >1 kDa) and truly dissolved (<1 kDa)
      fractions from river water. Clear patterns were observed, along the upland
      lowland land use continuum, in the partitioning and transport of macronutrients
      and metals between the colloidal, truly dissolved and acid-available particulate
      (>0.45 MUm, suspended) fractions. Of these operationally-defined fractions
      measured, colloids were generally more important for both macronutrient and metal
      transport in the upland than in the lowland rivers. The results suggest that
      organic moieties in truly dissolved form from sewage effluent may have a greater
      capacity to chelate metals. Organic-rich colloids in the upland moorlands and
      metal oxide colloidal precipitates in the industrial rivers had a higher capacity
      for binding metals than the colloidal fractions in the urban and agricultural
      lowland rivers. Aggregation of these colloids may provide an important mechanism
      for formation of larger suspended particulates, accounting for a higher degree of
      metal enrichment in the acid-available particulate fractions of the upland
      moorland and lowland industrial rivers, than in the lowland agricultural and
      urban rivers. This mechanism of transfer of contaminants to larger aggregates via
      colloidal intermediates, known as 'colloidal pumping' may also provide a
      mechanism for particulate P formation and the high proportion of P being
      transported in the particulate fraction in the uplands. The cross-flow
      ultrafiltration data also allowed refinement of partition coefficients, by
      accounting for colloids within the solids phase and replacing the filtered (<0.45
      MUm) fraction with the truly dissolved (<1 kDa) concentrations. These provided a
      clearer description of the controls on metal and P partitioning along the upland
      lowland continuum.

PMID- 22417884
TI  - The rapid shallow breathing index as a predictor of failure of noninvasive
      ventilation for patients with acute respiratory failure.
AB  - BACKGROUND: Noninvasive ventilation (NIV) may reduce the need for intubation in
      acute respiratory failure (ARF). However, there is no standard method to predict
      success or failure with NIV. The rapid shallow breathing index (RSBI) is a
      validated tool for predicting readiness for extubation.  We evaluated the ability
      of the RSBI to predict failure of NIV and mortality in ARF. METHODS: Prospective,
      observational trial of patients with ARF treated with NIV. NIV was initiated at
      the discretion of the clinicians, and an RSBI was recorded on the initial level
      of support (designated  as assisted RSBI [aRSBI]). Patients were categorized by
      initial aRSBI value as either high (aRSBI > 105) or low (aRSBI <= 105). The
      primary end point was need for intubation, and the secondary end point was in
      hospital mortality. Patients in the low and high aRSBI groups were compared 
      using univariate analysis, followed by multivariable logistic regression to
      determine the association between aRSBI groups and outcome. RESULTS: A total of
      101 patients were included. The majority of patients had an inspiratory pressure
      of 5-10 cm H(2)O in addition to an expiratory  pressure of 5-8 cm H(2)O. Of 83
      patients with an aRSBI <= 105, 26 (31%) required intubation, compared to 10/18
      (55%) with an aRSBI > 105 (multivariate odds ratio 3.70, 95% CI 1.14-11.99, P =
      .03). When comparing mortality, 7/83 patients (8.4%) with an aRSBI  <= 105 died,
      compared to 6/18 (33%) patients in the group with an aRSBI > 105 (multivariate
      odds ratio 4.51, 95% CI 1.19-17.11, P = .03). CONCLUSIONS: An aRSBI of > 105 is
      associated with need for intubation and increased in-hospital mortality. Whether
      patients with an  elevated aRSBI could also have benefitted from an increase in
      NIV settings remains unclear. Validation of this concept in a larger patient
      population is warranted.

PMID- 22417885
TI  - Quasiparticle states and quantum interference induced by magnetic impurities on a
      two-dimensional topological superconductor.
AB  - We theoretically study the effect of localized magnetic impurities on two
      dimensional topological superconductor (TSC). We show that the local density of
      states (LDOS) can be tuned by the effective exchange field m, the chemical
      potential MU of TSC, and the distance Deltar as well as the relative spin angle
      alpha between two impurities. The changes in Deltar between two impurities alter
      the interference and result in significant modifications to the bonding and
      antibonding states. Furthermore, the bound-state spin LDOS induced by single and
      double magnetic impurity scattering, the quantum corrals and the quantum mirages
      are also discussed. Finally, we briefly compare the impurities in TSC with those
      in topological insulators.

PMID- 22417886
TI  - Risk factors for the development of acute lung injury in patients with infectious
      pneumonia.
AB  - INTRODUCTION: Although pneumonia has been identified as the single most common
      risk factor for acute lung injury (ALI), we have a limited knowledge as to why
      ALI develops in some patients with pneumonia and not in others. The objective of
      this study was to determine frequency, risk factors, and outcome of ALI in
      patients with infectious pneumonia. METHODS: A retrospective cohort study of
      adult patients with microbiologically positive pneumonia, hospitalized at two
      Mayo Clinic Rochester hospitals between January 1, 2005, and December 31, 2007.
      In a subsequent nested case-control analysis, we evaluated the differences in
      prehospital and intrahospital exposures between patients with and without
      ALI/acute respiratory distress syndrome (ARDS) matched by specific pathogen,
      isolation site, gender, and closest age in a 1:1 manner. RESULTS: The study
      included 596 patients; 365 (61.2%) were men. The median age was 65 (IQR, 53 to
      75) years. In total, 171 patients (28.7%) were diagnosed with ALI. The occurrence
      of ALI was less frequent in bacterial (n = 99 of 412, 24%) compared with viral (n
      = 19 of 55, 35%), fungal (n = 39 of 95, 41%), and mixed isolates pneumonias (n =
      14 of 34, 41%; P = 0.002). After adjusting for baseline severity of illness and
      comorbidities, patients in whom ALI developed had a markedly increased risk of
      hospital death (ORadj 9.7; 95% CI, 6.0 to 15.9). In a nested case-control study,
      presence of shock (OR, 8.9; 95% CI, 2.8 to 45.9), inappropriate initial
      antimicrobial treatment (OR, 3.2; 95% CI, 1.3 to 8.5), and transfusions (OR, 4.8;
      95% CI, 1.5 to 19.6) independently predicted ALI development. CONCLUSIONS: The
      development of ALI among patients hospitalized with infectious pneumonia varied
      among pulmonary pathogens and was associated with increased mortality.
      Inappropriate initial antimicrobial treatment and transfusion predict the
      development of ALI independent of pathogen.

PMID- 22417887
TI  - Pharmacy workers' perceptions and acceptance of bar-coded medication technology
      in a pediatric hospital.
AB  - BACKGROUND: The safety benefits of bar-coded medication-dispensing and
      administration (BCMA) technology depend on its intended users favorably
      perceiving, accepting, and ultimately using the technology. OBJECTIVES: (1) To
      describe pharmacy workers' perceptions and acceptance of a recently implemented
      BCMA system and (2) to model the relationship between perceptions and acceptance
      of BCMA. METHODS: Pharmacists and pharmacy technicians at a Midwest U.S.
      pediatric hospital were surveyed following the hospital's implementation of a
      BCMA system. Twenty-nine pharmacists' and 10 technicians' self-reported
      perceptions and acceptance of the BCMA system were analyzed, supplemented by
      qualitative observational and free-response survey data. Perception-acceptance
      associations were analyzed using structural models. RESULTS: The BCMA system's
      perceived ease of use was rated low by pharmacists and moderate by pharmacy
      technicians. Both pharmacists and technicians perceived that the BCMA system was
      not useful for improving either personal job performance or patient care.
      Pharmacy workers perceived that individuals important to them encouraged BMCA
      use. Pharmacy workers generally intended to use BCMA but reported low
      satisfaction with the system. Perceptions explained 72% of the variance in
      intention to use BCMA and 79% of variance in satisfaction with BCMA. CONCLUSIONS:
      To promote their acceptance and use, BCMA and other technologies must be better
      designed and integrated into the clinical work system. Key steps to achieving
      better design and integration include measuring clinicians' acceptance and
      elucidating perceptions and other factors that shape acceptance.

PMID- 22417888
TI  - Source identification of petroleum hydrocarbons in soil and sediments from Iguacu
      River Watershed, Parana, Brazil using the CHEMSIC method (CHEMometric analysis of
      Selected Ion Chromatograms).
AB  - A chemometric method based on principal component analysis (PCA) of pre-processed
      and combined sections of selected ion chromatograms (SICs) is used to
      characterise the hydrocarbon profiles in soil and sediment from Araucaria,
      Guajuvira, General Lucio and Balsa Nova Municipalities (Iguacu River Watershed,
      Parana, Brazil) and to indicate the main sources of hydrocarbon pollution. The
      study includes 38 SICs of polycyclic aromatic compounds (PACs) and four of
      petroleum biomarkers in two separate analyses. The most contaminated samples are
      inside the Presidente Getulio Vargas Refinery area. These samples represent a
      petrogenic pattern and different weathering degrees. Samples from outside the
      refinery area are either less or not contaminated, or contain mixtures of
      diagenetic, pyrogenic and petrogenic inputs where different proportions
      predominate. The locations farthest away from industrial activity (Balsa Nova)
      contains the lowest levels of PAC contamination. There are no evidences to
      conclude positive matches between the samples from outside the refinery area and
      the Cusiana spilled oil.

PMID- 22417889
TI  - Study of the retention behavior in zwitterionic hydrophilic interaction
      chromatography of isomeric hydroxy- and aminobenzoic acids.
AB  - The retention behavior of fifteen isomeric hydroxy- and aminobenzoic acids in
      zwitterionic hydrophilic interaction chromatography was studied using a
      sulfobetaine phase (ZIC-HILIC). By an inspection of their molecular structures,
      the retention was related to the number, the position and hydrogen bond
      properties of the functional groups. The effect of the chromatographic conditions
      was analyzed in order to investigate the retention mechanism of the stationary
      phase. The increased retention observed for negative charged compounds when the
      mobile phase pH decreased was ascribed to a diminishing of the electrostatic
      repulsion with the underivatized silanol groups. Also the salt buffer
      concentration in the mobile was proved to have a great influence in the
      modulation of the electrostatic interactions. However, the retention behavior of
      the benzoic acids was not described by conventional ion-exchange models.
      Subsequently, a systematical analysis of partition, adsorption, and hydrophilic
      chromatographic models was presented. The results from the fittings indicated
      that partition processes govern mainly the ZIC-HILIC separation, but also
      adsorption processes via hydrogen bonds occurred for hydrogen donor analytes.
      Finally, the influence of the chromatographic conditions on the water enriched
      layer in which partition takes place has been evaluated by the elution behavior
      of toluene.

PMID- 22417890
TI  - Management and outcome of Ebstein's anomaly in children.
AB  - OBJECTIVES: To assess clinical presentation, treatment, and outcome of children
      with Ebstein's anomaly. BACKGROUND: Data on long-term outcome of children with
      Ebstein's anomaly are scarce. METHODS: Retrospective analysis of all children
      with Ebstein's anomaly treated between February, 1979 and January, 2009 in a
      single tertiary institution. Primary outcomes included patient survival and need
      for intervention, either cardiac surgery or catheter intervention. RESULTS: A
      total of 42 patients were diagnosed with Ebstein's anomaly at a median age of 5
      days ranging from 1 day to 11.7 years. Symptoms included cyanosis, heart murmur,
      and/or dyspnoea. Associated cardiac anomalies occurred in 90% of the patients.
      Average follow-up was 9.5 plus or minus 7.0 years. The overall mortality rate was
      14%. Of the six patients, three died postnatally before treatment. Cardiac
      surgery and/or catheter-guided interventions were required in 33 patients (79%).
      Cardiac surgery was performed in 21 (50%) patients at a median age of 9.1 years
      (range 0.1-16.5 years), including biventricular repair in 13 (62%), one-and-a
      half chamber repair in seven (33%), and a staged single-ventricle repair in one.
      Peri-operative mortality was 4%. Catheter-guided interventions consisted of
      device closure of an atrial septal defect in three cases and radiofrequency
      ablation of accessory pathways in nine patients. The estimated 10-year survival
      was 85.3 plus or minus 5.6%. CONCLUSION: In children, Ebstein's anomaly is
      usually diagnosed in the first year of age. Even though children with Ebstein's
      anomaly often require an intervention, their peri-operative mortality is low and
      long-term survival is good. Symptomatic newborns requiring an intervention may
      have a worse outcome.

PMID- 22417892
TI  - PTH-mediated inhibition of the renal transport of phosphate.

PMID- 22417894
TI  - Relapsing polychondritis in the Department of Defense population and review of
      the literature.
AB  - OBJECTIVE: The objective of this study was to characterize the clinical features
      of relapsing polychondritis (RPC) within the Department of Defense beneficiary
      population and determine the utility of echocardiography, imaging studies, and
      pulmonary function testing for diagnosis and monitoring disease. METHODS: We
      performed a retrospective Electronic Medical Record chart review of all patients
      diagnosed with RPC within the Department of Defense between January 2004 and
      December 2009. RESULTS: Thirty patients met McAdam's diagnostic criteria and an
      additional 13 met our criteria for partial RPC. Auricular chondritis (88%),
      inflammatory eye disease (57%), and arthritis (60%) were the most common clinical
      manifestations. Pulmonary involvement was seen in 16 (37%) patients. Methotrexate
      (42%) and corticosteroids (21%) were the most conventional therapies. Thirty
      (70%) patients had pulmonary function tests with flow volume loop abnormalities
      observed in 33%. Chest computed tomography was performed in 63%, with
      abnormalities in 48%. Abnormalities on echocardiography were observed in 12 of 25
      (48%) patients. CONCLUSIONS: The incidence, demographic data, and organ
      involvement in our RPC patients were similar to previous studies. The diagnosis
      of RPC was determined primarily on physical examination and symptom-driven
      diagnostic testing. There was no notable pattern by rheumatologists for
      monitoring the progression of tracheobronchial tree or large vessel involvement.
      Interpreting flow volume loops is recommended with pulmonary function testing to
      detect early laryngotracheal involvement. Computed tomography of the chest is
      also recommended to monitor for vascular and tracheobronchial tree involvement.

PMID- 22417893
TI  - The role of cell-extracellular matrix interactions in glomerular injury.
AB  - Glomerulosclerosis is characterized by excessive deposition of extracellular
      matrix within the glomeruli of the kidney, glomerular cell death, and subsequent
      loss of functional glomeruli. While in physiological situations the levels of
      extracellular matrix components are kept constant by a tight balance between
      formation and degradation, in the case of injury that results in fibrosis there
      is increased matrix deposition relative to its breakdown. Multiple factors
      control matrix synthesis and degradation, thus contributing to the development of
      glomerulosclerosis. This review focuses primarily on the role of cell-matrix
      interactions, which play a critical role in governing glomerular cell cues in
      both healthy and diseased kidneys. Cell-extracellular matrix interactions are
      made possible by various cellular receptors including integrins, discoidin domain
      receptors, and dystroglycan. Upon binding to a selective extracellular matrix
      protein, these receptors activate intracellular signaling pathways that can
      either downregulate or upregulate matrix synthesis and deposition. This, together
      with the observation that changes in the expression levels of matrix receptors
      have been documented in glomerular disease, clearly emphasizes the contribution
      of cell-matrix interactions in glomerular injury. Understanding the molecular
      mechanisms whereby extracellular matrix receptors regulate matrix homeostasis in
      the course of glomerular injury is therefore critical for devising more effective
      therapies to treat and ideally prevent glomerulosclerosis.

PMID- 22417895
TI  - Anaerobic digestion of glycerol and co-digestion of glycerol and pig manure.
AB  - The potential of glycerol obtained from transesterification of waste cooking oil
      as a main carbon source for biogas production was investigated. The glycerol was
      highly contaminated with oils and fats and was pretreated with sulfuric acid.
      Using a carbon source of glucose as a control, we compared biogas production from
      the acid-treated glycerol in a synthetic medium and the acid-treated glycerol
      mixed with pig manure. The anaerobic digestion of acid-treated glycerol with
      supplement in a synthetic medium was found to be satisfactory at organic loading
      rates (OLR) between 1.3, 1.6 and 2.6 g chemical oxygen demand (COD) L(-1) d(-1).
      The maximum methane yield of 0.32 L at Standard temperature and pressure (STP) g(
      1) COD removal was achieved at an OLR of 1.6 g COD L(-1) d(-1) and the methane
      content was 54% on an average. At a higher organic loading rate of 5.4 g COD L(
      1) d(-1), the propionic acid to acetic acid ratio was higher than the critical
      threshold limit for metabolic imbalance. Anaerobic digestion of acid-treated
      glycerol with pig manure was also investigated at the COD ratio of 80:20
      (glycerol:pig manure). The anaerobic digestion of acid-treated glycerol with pig
      manure was found to be satisfactory at organic loading rates between 1.3, 1.7,
      2.9 and 5.0 g COD L(-1) d(-1) in terms of COD reduction (>80%) and methane
      content of (62% on an average). However, the biogas production rate was found to
      significantly decrease at the highest load. The maximum methane yield of 0.24 L
      STP g(-1) COD removal was achieved at an OLR of 1.3 g COD L(-1) d(-1).

PMID- 22417896
TI  - Relationship of caregiver and family functioning to participation outcomes after
      postacute rehabilitation for traumatic brain injury: a multicenter investigation.
AB  - OBJECTIVE: To investigate the contribution of caregiver emotional functioning and
      family functioning to participation outcomes after postacute rehabilitation for
      traumatic brain injury (TBI). DESIGN: Prospective cohort study. SETTING: Three
      postacute comprehensive-integrated postacute rehabilitation programs associated
      with National Institute on Disability and Rehabilitation Research-funded TBI
      Model Systems Centers. PARTICIPANTS: Persons with medically documented TBI
      (N=136; 57% with severe TBI, 12% moderate, 31% mild), primarily men and 69%
      white. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Community
      Integration Questionnaire and Craig Handicap Assessment and Reporting Technique
      (CHART). RESULTS: After accounting for age, education, sex, and race/ethnicity,
      there was a significant interaction between caregiver emotional functioning and
      time since injury for CHART Occupation and Social Integration Scale scores.
      Better emotional functioning in caregivers was associated with greater occupation
      and social integration outcomes for persons who entered the postacute
      rehabilitation program within 6 months of injury, but not for those >6 months
      postinjury. There was no relationship of family functioning to participation
      outcomes, and no interaction between family functioning and time since injury.
      CONCLUSIONS: Caregiver distress should be accounted for in studies investigating
      the effectiveness of postacute rehabilitation after TBI. Screening of caregivers
      early during postacute rehabilitation can target those who need assistance to
      improve their support of the person with TBI.

PMID- 22417897
TI  - Polymorphisms of interleukin-1 and interleukin-6 genes on the risk of ischemic
      stroke in a meta-analysis.
AB  - Many epidemiological studies have investigated the associations between
      polymorphisms of interleukin-1 (IL1) and interleukin-6 (IL6) genes and risk of
      ischemic stroke (IS), but no conclusions are available because of conflicting
      results. The aim of this study was to assess the relationships by meta-analysis.
      The databases of Pubmed, Embase and Wangfang, updated to August 1st, 2011, were
      retrieved. Odds ratio (OR) and corresponding 95% confidence interval (95% CI) as
      effect size were calculated by a fixed- or random-effect model. In total, three
      case-control studies for IL1alpha-889C/T, eight studies for IL1beta-511C/T, eight
      studies for IL1-Ra and seven studies for IL6-147G/C were included in this meta
      analysis. Combined analysis indicated that IL1beta-511C/T polymorphism was not
      overall associated with risk of IS [OR (95% CI)=1.22 (0.85-1.87) for TT vs. CC].
      However, when subgroup analyses for countries were conducted, the results
      indicated that T allele was associated with increased risk of IS for Polish and
      associated with a trend of increased risk of IS for Chinese although it did not
      reach statistical significance [TT vs. CC: OR (95% CI)=1.97 (1.22-3.17) for
      Polish and 1.40 (0.99-1.99) for Chinese]. In addition, overall and subgroup
      analyses indicated that IL1alpha-889C/T, IL1-Ra and IL6-147G/C polymorphisms were
      also not associated with risk of IS [OR (95% CI)=1.21 (0.86-1.70) for TT vs. CC
      of IL1alpha-889C/T, 1.22 (0.85-1.75) for RN2/RN2 vs. RN1/RN1 for IL1-Ra and 1.09
      (0.84-1.40) for G carriers vs. C carriers for IL6-147G/C]. This study inferred
      that IL1beta-511C/T polymorphism might be moderately associated with increased
      risk of IS, but no sufficient evidence was available to support any associations
      between IL1-Ra and IL6-147G/C polymorphisms and IS. We could not draw a
      conclusion between IL1alpha-889C/T polymorphism and risk of IS based on the
      limited data, and further large sample-sized studies were required.

PMID- 22417898
TI  - Expression of candidate genes related to metabolism, immunity and cellular stress
      during massive mortality in the American oyster Crassostrea virginica larvae in
      relation to biochemical and physiological parameters.
AB  - Quantification of mRNA of genes related to metabolism, immunity and cellular
      stress was examined in relation to a massive mortality event during the culture
      of American oyster larvae, Crassostrea virginica which was probably, in regard to
      previous microbiological analysis, induced by Vibrio infection. To document
      molecular changes associated with the mortality event, mRNA levels were compared
      to biochemical and physiological data, previously described in a companion paper.
      Among the 18 genes studied, comparatively to the antibiotic control, 10 showed a
      lower relative gene expression when the massive mortality occurred. Six of them
      are presumed to be related to metabolism, corroborating the metabolic depression
      associated with the mortality event suggested by biochemical and physiological
      analyses. Relationships between the regulation of antioxidant enzyme activities,
      lipid peroxidation, and the mRNA abundance of genes linked to oxidative stress,
      cytoprotection, and immune response are also discussed. Finally, we observed an
      increase in the transcript abundance of two genes involved in apoptosis and cell
      regulation simultaneously with mortality, suggesting that these processes might
      be linked.

PMID- 22417899
TI  - Optimization and quality assurance of an image-guided radiation therapy system
      for intensity-modulated radiation therapy radiotherapy.
AB  - To develop a quality assurance (QA) of XVI cone beam system (XVIcbs) for its
      optimal imaging-guided radiotherapy (IGRT) implementation, and to construe
      prostate tumor margin required for intensity-modulated radiation therapy (IMRT)
      if IGRT is unavailable. XVIcbs spatial accuracy was explored with a humanoid
      phantom; isodose conformity to lesion target with a rice phantom housing a soap
      as target; image resolution with a diagnostic phantom; and exposure validation
      with a Radcal ion chamber. To optimize XVIcbs, rotation flexmap on coincidency
      between gantry rotational axis and that of XVI cone beam scan was investigated.
      Theoretic correlation to image quality of XVIcbs rotational axis stability was
      elaborately studied. Comprehensive QA of IGRT using XVIcbs has initially been
      explored and then implemented on our general IMRT treatments, and on special IMRT
      radiotherapies such as head and neck (H and N), stereotactic radiation therapy
      (SRT), stereotactic radiosurgery (SRS), and stereotactic body radiotherapy
      (SBRT). Fifteen examples of prostate setup accounted for 350 IGRT cone beam
      system were analyzed. IGRT accuracy results were in agreement +/- 1 mm. Flexmap
      0.25 mm met the manufacturer's specification. Films confirmed isodose coincidence
      with target (soap) via XVIcbs, otherwise not. Superficial doses were measured
      from 7.2-2.5 cGy for anatomic diameters 15-33 cm, respectively. Image quality was
      susceptible to rotational stability or patient movement. IGRT using XVIcbs on
      general IMRT treatments such as prostate, SRT, SRS, and SBRT for setup accuracy
      were verified; and subsequently coordinate shifts corrections were recorded. The
      350 prostate IGRT coordinate shifts modeled to Gaussian distributions show
      central peaks deviated off the isocenter by 0.6 +/- 3.0 mm, 0.5 +/- 4.5 mm in the
      X(RL)- and Z(SI)-coordinates, respectively; and 2.0 +/- 3.0 mm in the Y(AP)
      coordinate as a result of belly and bladder capacity variations. Sixty-eight
      percent of confidence was within +/- 4.5 mm coordinates shifting. IGRT using
      XVIcbs is critical to IMRT for prostate and H and N, especially SRT, SRS, and
      SBRT. To optimize this modality of IGRT, a vigilant QA program is indispensable.
      Prostate IGRT reveals treatment accuracy as subject to coordinates' adjustments;
      otherwise a 4.5-mm margin is required to allow for full dose coverage of the
      clinical target volume, notwithstanding toxicity to normal tissues.

PMID- 22417900
TI  - Mechanisms underlying REBT in mood disordered patients: predicting depression
      from the hybrid model of learning.
AB  - BACKGROUND: Jackson's (2005, 2008a) hybrid model of learning identifies a number
      of learning mechanisms that lead to the emergence and maintenance of the balance
      between rationality and irrationality. We test a general hypothesis that
      Jackson's model will predict depressive symptoms, such that poor learning is
      related to depression. We draw comparisons between Jackson's model and Ellis'
      (2004) Rational Emotive Behavior Therapy and Theory (REBT) and thereby provide a
      set of testable learning mechanisms potentially underlying REBT. METHODS AND
      RESULTS: Results from 80 patients diagnosed with depression completed the
      learning styles profiler (LSP; Jackson, 2005) and two measures of depression.
      Results provide support for the proposed model of learning and further evidence
      that low rationality is a key predictor of depression. CONCLUSIONS: We conclude
      that the hybrid model of learning has the potential to explain some of the
      learning and cognitive processes related to the development and maintenance of
      irrational beliefs and depression.

PMID- 22417901
TI  - CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant
      Haemorrhage) intracranial bleeding study: the effect of tranexamic acid in
      traumatic brain injury--a nested randomised, placebo-controlled trial.
AB  - BACKGROUND: Tranexamic acid (TXA) has been shown to reduce blood loss in surgical
      patients and the risk of death in patients with traumatic bleeding, with no
      apparent increase in vascular occlusive events. These findings raise the
      possibility that it might also be effective in traumatic brain injury (TBI).
      OBJECTIVE: The Clinical Randomisation of an Antifibrinolytic in Significant
      Haemorrhage Intracranial Bleeding Study (CRASH-2 IBS) was conducted to quantify
      the effect of an early short course of TXA on intracranial haemorrhage and new
      focal cerebral ischaemic lesions in patients with TBI. DESIGN: CRASH-2 IBS was a
      prospective randomised controlled trial nested within the CRASH-2 trial.
      Randomisation was balanced by centre, with an allocation sequence based on a
      block size of eight. We used a local pack system that selected the lowest
      numbered treatment pack from a box containing eight numbered packs. Apart from
      the pack number, the treatment packs were identical. The pack number was recorded
      on the entry form, which was sent to the international trial co-ordinating centre
      in London, UK. Once the treatment pack number was recorded, the patient was
      included in the trial whether or not the treatment pack was opened or the
      allocated treatment started. All site investigators and trial co-ordinating
      centre staff were masked to treatment allocation. SETTING: Ten hospitals: (India)
      Aditya Neuroscience Centre, Sanjivani Hospital, CARE Hospital, Christian Medical
      College, Medical Trust Hospital, Jeevan Jyoti Hospital and (Colombia) Hospital
      Universitario San Vicente de Paul, Hospital Pablo Tobon Uribe, Hospital
      Universitario San Jose de Popayan and Fundacion Valle del Lili. PARTICIPANTS: The
      trial was conducted in a subset of 270 CRASH-2 trial participants. Patients
      eligible for inclusion in the CRASH-2 IBS fulfilled the inclusion criteria for
      the CRASH-2 trial, and also had TBI [Glasgow Coma Scale score of <= 14 and a
      brain computerised tomography (CT) scan compatible with TBI]. Pregnant women and
      patients for whom a second brain CT scan was not possible were excluded.
      INTERVENTIONS: Participants were randomly allocated to receive either a loading
      dose of 1 g of TXA infused over 10 minutes followed by an intravenous infusion of
      1 g over 8 hours or matching placebo. MAIN OUTCOME MEASURE: The primary outcome
      was the increase in size of intracranial haemorrhage growth between a CT scan at
      hospital admission and a second scan 24-48 hours later. RESULTS: One hundred and
      thirty-three patients were allocated to TXA and 137 to placebo, of whom
      information on the primary (imaging) outcome was available for 123 (92%) and 126
      (92%) respectively. The analysis suggested that TXA was likely to be associated
      with a reduction in haemorrhage growth [adjusted difference -3.8 ml, 95%
      credibility interval (CrI) -11.5 ml to 3.9 ml], fewer focal ischaemic lesions
      [adjusted odds ratio (OR) 0.54, 95% CrI 0.20 to 1.46] and fewer deaths (adjusted
      OR 0.49, 95% CrI 0.22 to 1.06). CONCLUSIONS: This was the first randomised
      controlled study to evaluate the effect of TXA in TBI patients and it found that
      neither moderate benefits nor moderate harmful effects can be excluded. However,
      although uncertainty remains, our analyses suggest that TXA administration might
      improve outcome in TBI patients and provide grounds for evaluating this
      hypothesis in future research. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN86750102. SOURCE OF FUNDING: This project was funded by the NIHR Health
      Technology Assessment programme and will be published in full in Health
      Technology Assessment; Vol. 16, No. 13. See the HTA programme website for further
      project information.

PMID- 22417902
TI  - Energy band gap engineering in borate ultraviolet nonlinear optical crystals: ab
      initio studies.
AB  - The development of ultraviolet (UV) nonlinear optical (NLO) crystals demands
      optical materials with wide energy band gaps. Here we report first-principles
      studies on the electronic structures in several UV NLO borates with
      representative structures. Combined with model analysis, we find that the oxygen
      non-bonding 2p orbitals play an important role on the top of valence bands. The
      energy band gap can be adjusted by modifying the coordination environment around
      the oxygen atoms. Under ideal conditions the energy band gaps achieve 9 eV if the
      non-bonding orbitals are totally eliminated, despite the original values varying
      from 6.6 to 8.3 eV.

PMID- 22417903
TI  - New challenges in detecting, grading, and staging endometrial cancer after
      uterine morcellation.
AB  - STUDY OBJECTIVE: To evaluate the accuracy in diagnosing endometrial disease after
      uterine morcellation. DESIGN: Prospective case series. SETTING: University
      medical center. PATIENTS: Five women undergoing hysterectomy without morcellation
      because of benign indications and 5 women with endometrial cancer. INTERVENTIONS:
      Uterine specimens were obtained from all 10 study patients. The uteri were sent
      for pathologic analysis, processed, and fixed according to standard protocols. A
      single investigator then morcellated all 10 uteri. A single pathologist blinded
      to specimen group reviewed each specimen. MAIN RESULTS: The pathologist
      identified endometrial cancer in 4 of 5 specimens of known cancer. The fifth
      specimen was interpreted as benign despite the presence of grade 1, stage IA
      endometrial adenocarcinoma. None of the morcellated specimens could be staged.
      CONCLUSION: The increasing use of uterine morcellation will result in new
      challenges for gynecologic oncologists secondary to difficulty in detection, and
      accurate grading and staging of endometrial cancer.

PMID- 22417904
TI  - Direct aspiration endometrial biopsy via flexible hysteroscopy.
AB  - STUDY OBJECTIVE: To determine feasibility and efficacy of direct aspiration
      endometrial biopsy via the fluid channel of a flexible diagnostic hysteroscope.
      DESIGN: Retrospective review (Canadian Task Force classification II-3). SETTING:
      Abnormal uterine bleeding clinic in a tertiary care center. PATIENTS: All women
      who underwent direct aspiration endometrial biopsy from January 2007 through
      August 2011 via a flexible diagnostic hysteroscope because traditional office
      based endometrial biopsy using a suction piston device was not technically
      possible. INTERVENTIONS: Diagnostic hysteroscopy followed by direct aspiration
      endometrial biopsy, accomplished by applying suction to the fluid channel of a
      3.1-mm flexible diagnostic hysteroscope via a 10-mL syringe. The hysteroscope tip
      was agitated within the uterine cavity to obtain a tissue sample. MEASUREMENTS
      AND MAIN RESULTS: The median age of the 32 identified patients was 50 years; 18
      women (56%) were nulliparous, and 10 (31%) were postmenopausal. Thirty-one
      patients underwent hysteroscopy/direct aspiration biopsy because of abnormal
      uterine bleeding or postmenopausal bleeding. The vaginoscopic approach was used
      in 19 patients (59%). Indications for direct aspiration endometrial biopsy
      included cervical stenosis, inability to pass the endometrial biopsy instrument
      into the uterine cavity, and patient intolerance of endometrial biopsy. Adequate
      endometrial samples were obtained in 28 patients (87.5%). In 3 of 4 patients in
      whom direct aspiration endometrial biopsy did not provide sufficient tissue,
      hysteroscopy revealed an atrophic-appearing endometrium. The direct aspiration
      endometrial biopsy diagnosis was confirmed in 5 of 7 patients who subsequently
      underwent dilation and curettage or hysterectomy. CONCLUSION: Direct aspiration
      endometrial biopsy is a simple and effective endometrial sampling method when
      traditional office-based endometrial biopsy is not feasible. Further prospective
      studies including larger populations are needed to confirm these results.

PMID- 22417905
TI  - Topical anesthetic (lidocaine-prilocaine) cream application before speculum
      examination in postmenopausal women.
AB  - STUDY OBJECTIVE: To evaluate the effectiveness of lidocaine-prilocaine (EMLA 5%)
      cream application to genital mucosa for reducing pain or discomfort associated
      with speculum examination in postmenopausal women. DESIGN: A randomized
      controlled study (Canadian Task Force classification I). SETTING: A university
      hospital. PATIENTS: One-hundred thirty-four postmenopausal women. INTERVENTIONS:
      The subjects were randomized to an EMLA cream group, a lubricant gel group, or a
      control group. General data was collected, including age, body weight, gravidity,
      parity, smoking habits, history of diabetes mellitus, previous gynecologic
      operations, dyspareunia, sexual activity, and duration of menopause. All patients
      were asked to score pain at 3 time points (insertion, dilation, and extraction of
      speculum) during the procedure using a visual analog scale. Pain intensity during
      speculum examination was compared between the groups. MEASUREMENTS AND MAIN
      RESULTS: There was no statistically significant difference between the EMLA
      cream, the lubricant gel, and the control groups in terms of age, weight,
      gravidity, parity, dyspareunia, duration of menopause, sexual activity, smoking
      habit, diabetes mellitus, previous vaginal and other gynecological procedures,
      vaginal length, and serum follicle-stimulating hormone and estradiol levels (p >
      .05). The pain scores obtained during all phases of speculum application were
      significantly lower in the EMLA group than in both the lubricant gel and the
      control groups (p < .001). Comparing the gel and the control groups, a lower pain
      score was observed in the former, except for the second phase of the examination
      (p < .001). CONCLUSION: Topical application of EMLA 5% cream on genital mucosa of
      postmenopausal women before vaginal examination significantly reduces pain
      associated with speculum application.

PMID- 22417906
TI  - Orifice-assisted small-incision surgery: case series in benign and oncologic
      gynecology.
AB  - This case series describes the feasibility of orifice-assisted small-incision
      surgery (OASIS), a novel technique that may incorporate benefits of single
      incision and natural-orifice surgery while minimizing issues such as instrument
      crowding and interaction of optical access with operative instrumentation. In our
      multiple-site series, we included patients from a large academic medical center
      in the northeastern United States and a private gynecology clinic in India.
      Between the 2 centers, a total of 14 patients (5 with benign disease and 9 with
      oncologic disease) underwent the following procedures: OASIS total laparoscopic
      hysterectomy, laparoscopic supracervical hysterectomy, laparoscopic myomectomy,
      or laparoscopic radical hysterectomy with pelvic lymph node dissection. The
      initial 14 cases were safely completed. Oncologic clearance was consistent with
      specialty norms. Operating time ranged from 60 to 150 minutes, and estimated
      blood loss ranged from 10 to 500 mL. Detailed procedure descriptions and videos
      are provided. Based on preliminary case series experience, OASIS seems to be a
      safe and feasible addition to the advanced minimally invasive surgeons'
      armamentarium for both benign and oncologic cases.

PMID- 22417907
TI  - The relationship between skeletal muscle oxygenation and systemic oxygen uptake
      during exercise in subjects with COPD: a preliminary study.
AB  - BACKGROUND: Muscle oxygenation correlates with systemic oxygen uptake (V(O2)) in
      normal subjects; however, whether this relationship exists in COPD patients
      remains unclear. The purpose of this study was to investigate the influence of
      skeletal muscle oxygenation on V(O2) during exercise in patients with COPD.
      METHODS: Eight subjects performed an incremental cycle ergometer exercise test.
      We measured ventilation and pulmonary gas exchange with a metabolic measurement
      system. We also continuously monitored S(pO2), and measured tissue oxygen
      saturation (S(tO2)) in the vastus lateralis with continuous-wave near-infrared
      spectroscopy. We calculated the muscle oxygen extraction rate (MOER) based on
      S(pO2) and S(tO2). In addition, we calculated Pearson correlation coefficients to
      examine the relationships between the V(O2) obtained during exercise testing and
      the mean values of S(pO2), S(tO2), heart rate (HR), and MOER for each 30-second
      interval of the tests. Finally, we analyzed the relationships between the peak
      V(O2) and the slopes of HR/V(O2), S(pO2)/V(O2), S(tO2)/V(O2), and MOER/V(O2).
      RESULTS: With the increasing exercise intensity, many subjects showed a gradual
      decrease in S(tO2) and S(pO2), but a gradual increase in HR and MOER. V(O2) was
      negatively correlated with S(tO2) and S(pO2), and was positively correlated with
      HR and MOER. However, peak V(O2) was not correlated with any of the slopes.
      CONCLUSIONS: V(O2) is highly influenced by oxygen utilization in exercising
      muscles, as well as by blood oxygenation levels and cardiac function. However,
      the impact of skeletal muscle utilization during exercise on peak V(O2) varied
      greatly among the subjects.

PMID- 22417908
TI  - Regulation of oscillation dynamics in biochemical systems with dual negative
      feedback loops.
AB  - Feedback controls are central to cellular regulation. Negative-feedback
      mechanisms are well known to underline oscillatory dynamics. However, the
      presence of multiple negative-feedback mechanisms is common in oscillatory
      cellular systems, raising intriguing questions of how they cooperate to regulate
      oscillations. In this work, we studied the dynamical properties of a set of
      general biochemical motifs with dual, nested negative-feedback structures. We
      showed analytically and then confirmed numerically that, in these motifs, each
      negative-feedback loop exhibits distinctly different oscillation-controlling
      functions. The longer, outer feedback loop was found to promote oscillations,
      whereas the short, inner loop suppresses and can even eliminate oscillations. We
      found that the position of the inner loop within the coupled motifs affects its
      repression strength towards oscillatory dynamics. Bifurcation analysis indicated
      that emergence of oscillations may be a strict parametric requirement and thus
      evolutionarily tricky. Investigation of the quantitative features of oscillations
      (i.e. frequency, amplitude and mean value) revealed that coupling negative
      feedback provides robust tuning of the oscillation dynamics. Finally, we
      demonstrated that the mitogen-activated protein kinase (MAPK) cascades also
      display properties seen in the general nested feedback motifs. The findings and
      implications in this study provide novel understanding of biochemical negative
      feedback regulation in a mixed wiring context.

PMID- 22417909
TI  - Assessing the impact of adherence to anti-retroviral therapy on treatment failure
      and resistance evolution in HIV.
AB  - The adherence of patients to therapy is a crucial factor for successful HIV anti
      retroviral therapy. Imperfect adherence may lead to treatment failure, which can
      cause the emergence of resistance within viral populations. We have developed a
      stochastic model that incorporates compartments of latently infected cells and
      virus genotypes with different susceptibilities to three simultaneously used
      drugs. With this model, we study the impact of several key parameters on the
      probability of treatment failure, i.e. insufficient viral suppression, and the
      emergence of resistance. Specifically, we consider the impact of drug dosage,
      drug half-lives, fitness costs for resistance, different basic reproductive
      numbers of the virus and the influence of pre-existing mutations under various
      levels of adherence. Furthermore, we also investigate the influence of different
      temporal distributions of non-adherent days (drug holidays) during a treatment.
      Factors that promote resistance evolution include a high reproductive number,
      extended drug holidays and poor adherence. Pre-existing mutations only have a
      substantial effect if they confer resistance against more than one drug. Overall,
      our study highlights the importance of the interactions between imperfect
      adherence, pharmacodynamics, pharmacokinetics and latently infected cells for our
      understanding of drug resistance and therapy failure in HIV anti-retroviral
      therapy.

PMID- 22417910
TI  - Apatite-forming ability of titanium in terms of pH of the exposed solution.
AB  - In order to elucidate the main factor governing the capacity for apatite
      formation of titanium (Ti), Ti was exposed to HCl or NaOH solutions with
      different pH values ranging from approximately 0 to 14 and then heat-treated at
      600 degrees C. Apatite formed on the metal surface in a simulated body fluid,
      when Ti was exposed to solutions with a pH less than 1.1 or higher than 13.6,
      while no apatite formed upon exposure to solutions with an intermediate pH value.
      The apatite formation on Ti exposed to strongly acidic or alkaline solutions is
      attributed to the magnitude of the positive or negative surface charge,
      respectively, while the absence of apatite formation at an intermediate pH is
      attributed to its neutral surface charge. The positive or negative surface charge
      was produced by the effect of either the acidic or alkaline ions on Ti,
      respectively. It is predicted from the present results that the bone bonding of
      Ti depends upon the pH of the solution to which it is exposed, i.e. Ti forms a
      bone-like apatite on its surface in the living body and bonds to living bone
      through the apatite layer upon heat treatment after exposure to a strongly acidic
      or alkaline solution.

PMID- 22417911
TI  - Spatio-temporal development of the endothelial glycocalyx layer and its
      mechanical property in vitro.
AB  - The endothelial glycocalyx is a thin layer of polysaccharide matrix on the
      luminal surface of endothelial cells (ECs), which contains sulphated
      proteoglycans and glycoproteins. It is a mechanotransducer and functions as an
      amplifier of the shear stress on ECs. It controls the vessel permeability and
      mediates the blood-endothelium interaction. This study investigates the spatial
      distribution and temporal development of the glycocalyx on cultured ECs, and
      evaluates mechanical properties of the glycocalyx using atomic force microscopy
      (AFM) nano-indentation. The glycocalyx on human umbilical vein endothelial cells
      (HUVECs) is observed under a confocal microscope. Manipulation of the glycocalyx
      is achieved using heparanase or neuraminidase. The Young's modulus of the cell
      membrane is calculated from the force-distance curve during AFM indentation.
      Results show that the glycocalyx appears predominantly on the edge of cells in
      the early days in culture, e.g. up to day 5 after seeding. On day 7, the
      glycocalyx is also seen in the apical area of the cell membrane. The thickness of
      the glycocalyx is approximately 300 nm-1 MUm. AFM indentation reveals the Young's
      modulus of the cell membrane decreases from day 3 (2.93 +/- 1.16 kPa) to day 14
      (0.35 +/- 0.15 kPa) and remains unchanged to day 21 (0.33 +/- 0.19 kPa).
      Significant difference in the Young's modulus is also seen between the apical
      (1.54 +/- 0.58 kPa) and the edge (0.69 +/- 0.55 kPa) of cells at day 7. By
      contrast, neuraminidase-treated cells (i.e. without the glycocalyx) have similar
      values between day 3 (3.18 +/- 0.88 kPa), day 14 (2.12 +/- 0.78 kPa) and day 21
      (2.15 +/- 0.48 kPa). The endothelial glycocalyx in vitro shows temporal
      development in the early days in culture. It covers predominantly the edge of
      cells initially and appears on the apical membrane of cells as time progresses.
      The Young's modulus of the glycocalyx is deduced from Young's moduli of cell
      membranes with and without the glycocalyx layer. Our results show the glycocalyx
      on cultured HUVECs has a Young's modulus of approximately 0.39 kPa.

PMID- 22417912
TI  - On the thermodynamics of biomolecule surface transformations.
AB  - Biological surface science is receiving great and renewed attention owing the
      rising interest in applications of nanoscience and nanotechnology to biological
      systems, with horizons that range from nanomedicine and biomimetic photosynthesis
      to the unexpected effects of nanomaterials on health and environment. Biomolecule
      surface transformations are among the fundamental aspects of the field that
      remain elusive so far and urgently need to be understood to further the field.
      Our recent findings indicate that surface thermodynamics can give a substantial
      contribution toward this challenging goal. In the first part of the article, we
      show that biomolecule surface transformations can be framed by a general and
      simple thermodynamic model. Then, we explore its effectiveness by addressing some
      typical cases, including ligand-receptor surface binding, protein thin film
      machines, nanomechanical aspects of the biomolecule-nanoparticle interface and
      nanomechanical biosensors.

PMID- 22417913
TI  - A new database (GCD) on genome composition for eukaryote and prokaryote genome
      sequences and their initial analyses.
AB  - Eukaryote genomes contain many noncoding regions, and they are quite complex. To
      understand these complexities, we constructed a database, Genome Composition
      Database, for the whole genome composition statistics for 101 eukaryote genome
      data, as well as more than 1,000 prokaryote genomes. Frequencies of all possible
      one to ten oligonucleotides were counted for each genome, and these observed
      values were compared with expected values computed under observed oligonucleotide
      frequencies of length 1-4. Deviations from expected values were much larger for
      eukaryotes than prokaryotes, except for fungal genomes. Mammalian genomes showed
      the largest deviation among animals. The results of comparison are available
      online at http://esper.lab.nig.ac.jp/genome-composition-database/.

PMID- 22417914
TI  - Chaperones divide yeast proteins into classes of expression level and
      evolutionary rate.
AB  - It has long been known that many proteins require folding via molecular
      chaperones for their function. Although it has become apparent that folding
      imposes constraints on protein sequence evolution, the effects exerted by
      different chaperone classes are so far unknown. We have analyzed data of protein
      interaction with the chaperones in Saccharomyces cerevisiae using network
      methods. The results reveal a distinct community structure within the network
      that was hitherto undetectable with standard statistical tools. Sixty-four yeast
      chaperones comprise ten distinct modules that are defined by interaction
      specificity for their 2,691 interacting proteins. The classes of interacting
      proteins that are in turn defined by their dedicated chaperone modules are
      distinguished by various physiochemical protein properties and are characterized
      by significantly different protein expression levels, codon usage, and amino acid
      substitution rates. Correlations between substitution rate, codon bias, and gene
      expression level that have long been known for yeast are apparent at the level of
      the chaperone-defined modules. This indicates that correlated expression,
      conservation, and codon bias levels for yeast genes are attributable to
      previously unrecognized effects of protein folding. Proteome-wide categories of
      chaperone-substrate specificity uncover novel hubs of functional constraint in
      protein evolution that are conserved across 20 fungal genomes.

PMID- 22417915
TI  - The sex-specific impact of meiotic recombination on nucleotide composition.
AB  - Meiotic recombination is an important evolutionary force shaping the nucleotide
      landscape of genomes. For most vertebrates, the frequency of recombination varies
      slightly or considerably between the sexes (heterochiasmy). In humans, male,
      rather than female, recombination rate has been found to be more highly
      correlated with the guanine and cytosine (GC) content across the genome. In the
      present study, we review the results in human and extend the examination of the
      evolutionary impact of heterochiasmy beyond primates to include four additional
      eutherian mammals (mouse, dog, pig, and sheep), a metatherian mammal (opossum),
      and a bird (chicken). Specifically, we compared sex-specific recombination rates
      (RRs) with nucleotide substitution patterns evaluated in transposable elements.
      Our results, based on a comparative approach, reveal a great diversity in the
      relationship between heterochiasmy and nucleotide composition. We find that the
      stronger male impact on this relationship is a conserved feature of human, mouse,
      dog, and sheep. In contrast, variation in genomic GC content in pig and opossum
      is more strongly correlated with female, rather than male, RR. Moreover, we show
      that the sex-differential impact of recombination is mainly driven by the
      chromosomal localization of recombination events. Independent of sex, the higher
      the RR in a genomic region and the longer this recombination activity is
      conserved in time, the stronger the bias in nucleotide substitution pattern,
      through such mechanisms as biased gene conversion. Over time, this bias will
      increase the local GC content of the region.

PMID- 22417917
TI  - A preconception care program for women in a college setting.
AB  - Preconception healthcare is a way to enhance positive pregnancy outcomes by
      encouraging women to engage in healthy lifestyles before they become pregnant.
      Because approximately 50% of pregnancies are unplanned, fetal development may be
      affected before a woman receives prenatal care. Young women are especially
      vulnerable to poor outcomes due to risky behaviors. Education about preconception
      health is not common practice. This article describes a peer education
      preconception health program for college women that provided a basis for an
      expanded program with larger, more diverse populations. Nursing students as peer
      educators presented the program to over 100 young women using the mnemonic
      REFRAMED PLUS to address eight preconception risk areas and reproductive life
      planning. Materials to augment the program, developed by peer educators, included
      a brochure on preconception health, a risk assessment tool, a DVD with stories of
      young women who experienced unplanned pregnancies, and a Reproductive Life Plan
      book. Peer educators administered a pretest, showed the DVD, guided discussions,
      assessed each woman's health risks and administered a posttest. The risk
      assessment revealed that young women have several preconception health risks.
      Following the preconception program, posttest scores indicated increased
      knowledge of preconception health. For preconception healthcare to be successful,
      preconception risk assessments, education and counseling must be addressed by
      nurses every time a young woman receives care. When possible, peer educators
      should be used to disseminate the message to all women of childbearing age.

PMID- 22417918
TI  - Achieving baby-friendly designation: step-by-step.
AB  - The recent Surgeon General's Call to Action to Support Breastfeeding reinforces
      the important role breastfeeding has in the health of mothers and babies. It
      identifies the Baby-Friendly Hospital Initiative as a strategy that encompasses
      practices that result in better breastfeeding outcomes. Currently there are
      approximately 20,000 Baby-Friendly hospitals worldwide; however, only 125 of them
      are in the United States. This number is likely to increase with the renewed
      focus on breastfeeding. To achieve Baby-Friendly designation, hospitals and
      birthing centers must successfully implement the Baby-Friendly Ten Steps to
      Successful Breastfeeding, evidence-based guidelines designed to promote and
      support breastfeeding in maternity settings. The purpose of this article is to
      share specific strategies we used to successfully implement each of the Baby
      Friendly Ten Steps and improve our support and assistance of breastfeeding
      mothers and infants.

PMID- 22417919
TI  - Social distance and homophily in adolescent smoking initiation.
AB  - BACKGROUND: Studies often demonstrate homophily in adolescent smoking behavior,
      but rarely investigate the extent to which this is due to the peer network
      processes of selection versus influence. Applying the concept of social distance,
      this study examines these two processes for smoking initiation. METHODS: We
      analyzed socio-centric network data from the National Longitudinal Study of
      Adolescent Health (N=2065; grades=7th-12th). Social distance (degrees of
      separation), combined with stability and change in friendship networks, was used
      to derive indicators of peer selection and influence on initiation. Multilevel
      modeling was used to predict initiation from these indicators, and propensity
      score modeling was used to determine whether these associations remained after
      adjusting for pre-existing differences between initiators and consistent non
      smokers. RESULTS: We found that both peer influence and selection effects
      increased the likelihood of initiation even after adjusting with propensity score
      weights and demographic controls. While the effect size for peer influence
      depended on the overall proportion of smokers at the school, the selection effect
      was independent of the school environment. De-selection and indirect influence
      effects were not significant after controlling for school norm interactions.
      CONCLUSIONS: The association between peer smoking and adolescent smoking
      initiation appears to be due to both peer selection and direct influence.
      However, "friends of friends" effects are likely to be confounded with contextual
      factors. Given that smoking initiation is primarily associated with close
      personal interactions between the adolescent and his/her friends, prevention
      efforts should focus on the role of smoking in fostering personal relationships
      among adolescents.

PMID- 22417916
TI  - Widespread recurrent evolution of genomic features.
AB  - The recent explosion of genome sequences from all major phylogenetic groups has
      unveiled an unexpected wealth of cases of recurrent evolution of strikingly
      similar genomic features in different lineages. Here, we review the diverse known
      types of recurrent evolution in eukaryotic genomes, with a special focus on
      metazoans, ranging from reductive genome evolution to origins of splice-leader
      trans-splicing, from tandem exon duplications to gene family expansions. We first
      propose a general classification scheme for evolutionary recurrence at the
      genomic level, based on the type of driving force-mutation or selection-and the
      environmental and genomic circumstances underlying these forces. We then discuss
      various cases of recurrent genomic evolution under this scheme. Finally, we
      provide a broader context for repeated genomic evolution, including the unique
      relationship of genomic recurrence with the genotype-phenotype map, and the ways
      in which the study of recurrent genomic evolution can be used to understand
      fundamental evolutionary processes.

PMID- 22417920
TI  - Thin-slice perception develops slowly.
AB  - Body language and facial gesture provide sufficient visual information to support
      high-level social inferences from "thin slices" of behavior. Given short movies
      of nonverbal behavior, adults make reliable judgments in a large number of tasks.
      Here we find that the high precision of adults' nonverbal social perception
      depends on the slow development, over childhood, of sensitivity to subtle visual
      cues. Children and adult participants watched short silent clips in which a
      target child played with Lego blocks either in the (off-screen) presence of an
      adult or alone. Participants judged whether the target was playing alone or not;
      that is, they detected the presence of a social interaction (from the behavior of
      one participant in that interaction). This task allowed us to compare performance
      across ages with the true answer. Children did not reach adult levels of
      performance on this task until 9 or 10 years of age, and we observed an
      interaction between age and video reversal. Adults and older children benefitted
      from the videos being played in temporal sequence, rather than reversed,
      suggesting that adults (but not young children) are sensitive to natural movement
      in social interactions.

PMID- 22417921
TI  - The development of fine-grained sensitivity to eye contact after 6 years of age.
AB  - Adults use eye contact as a cue to the mental and emotional states of others.
      Here, we examined developmental changes in the ability to discriminate between
      eye contact and averted gaze. Children (6-, 8-, 10-, and 14-year-olds) and adults
      (n=18/age) viewed photographs of a model fixating the center of a camera lens and
      a series of positions to the left/right or upward/downward and judged whether the
      model's gaze was direct or averted to the left/right or upward/downward. The
      horizontal range of fixation positions leading to the perception of direct gaze
      (the cone of gaze) was more than 50% larger in 6-year-olds than in adults, but it
      was adult-like and smaller than the vertical cone of gaze by 8 years of age. The
      vertical cone of gaze was large and statistically adult-like by age 6, with only
      a small linear reduction thereafter. In all age groups, the horizontal cone of
      gaze was centered on the bridge of the participant's nose and the vertical cone
      was centered slightly below the participant's eye height. These findings indicate
      that until after age 6, relatively poor sensitivity to direct versus averted gaze
      limits children's ability to use gaze cues to make social judgments.

PMID- 22417922
TI  - Emerging perception of causality in action-and-reaction sequences from 4 to 6
      months of age: is it domain-specific?
AB  - Two experiments (N=136) studied how 4- to 6-month-olds perceive a simple
      schematic event, seen as goal-directed action and reaction from 3 years of age.
      In our causal reaction event, a red square moved toward a blue square, stopping
      prior to contact. Blue began to move away before red stopped, so that both
      briefly moved simultaneously at a distance. Primarily, our study sought to
      determine from what age infants see the causal structure of this reaction event.
      In addition, we looked at whether this causal percept depends on an animate style
      of motion and whether it correlates with tasks assessing goal perception and goal
      directed action. Infants saw either causal reactions or noncausal delayed control
      events in which blue started some time after red stopped. These events involved
      squares that moved either rigidly or nonrigidly in an apparently animate manner.
      After habituation to one of the four events, infants were tested on reversal of
      the habituation event. Spatiotemporal features reversed for all events, but
      causal roles changed only in reversed reactions. The 6-month-olds dishabituated
      significantly more to reversal of causal reaction events than to noncausal delay
      events, whereas younger infants reacted similarly to reversal of both. Thus,
      perceptual causality for reaction events emerges by 6 months of age, a younger
      age than previously reported but, crucially, the same age at which perceptual
      causality for launch events has emerged in prior research. On our second
      question, animate/inanimate motion had no effect at any age, nor did significant
      correlations emerge with our additional tasks assessing goal perception or goal
      directed object retrieval. Available evidence, here and elsewhere, is as
      compatible with a view that infants initially see A affecting B, without
      differentiation into physical or psychological causality, as with the standard
      assumption of distinct physical/psychological causal perception.

PMID- 22417923
TI  - Accurate segmentation of dense nanoparticles by partially discrete electron
      tomography.
AB  - Accurate segmentation of nanoparticles within various matrix materials is a
      difficult problem in electron tomography. Due to artifacts related to image
      series acquisition and reconstruction, global thresholding of reconstructions
      computed by established algorithms, such as weighted backprojection or SIRT, may
      result in unreliable and subjective segmentations. In this paper, we introduce
      the Partially Discrete Algebraic Reconstruction Technique (PDART) for computing
      accurate segmentations of dense nanoparticles of constant composition. The
      particles are segmented directly by the reconstruction algorithm, while the
      surrounding regions are reconstructed using continuously varying gray levels. As
      no properties are assumed for the other compositions of the sample, the technique
      can be applied to any sample where dense nanoparticles must be segmented,
      regardless of the surrounding compositions. For both experimental and simulated
      data, it is shown that PDART yields significantly more accurate segmentations
      than those obtained by optimal global thresholding of the SIRT reconstruction.

PMID- 22417924
TI  - Pharmacological manipulation of peroxisome proliferator-activated receptor gamma
      (PPARgamma) reveals a role for anti-oxidant protection in a model of Parkinson's
      disease.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists have been
      shown to provide neuroprotection in a number of neurodegenerative diseases
      including Parkinson's disease and Alzheimer's disease. These protective effects
      are primarily considered to result from the anti-inflammatory actions of
      PPARgamma, however, there is increasing evidence that anti-oxidant mechanisms may
      also contribute. This study explored the impact of the PPARgamma agonist
      rosiglitazone and the PPARgamma antagonist GW9662 in the MPP(+)/MPTP (1-methyl-4
      phenylpyridinium/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of
      Parkinson's disease, focussing on oxidative stress mechanisms. Rosiglitazone
      attenuated reactive oxygen species formation induced by MPP(+) in SH-SY5Y cells
      concurrent with an upregulation of glutathione-S-transferase activity, but not
      superoxide dismutase activity. These responses were not attenuated by cotreatment
      with GW9662 suggesting that PPARgamma activation is not required. The
      localisation of PPARgamma in vivo to dopaminergic neurons of the substantia nigra
      pars compacta (SNpc) was established by immunohistochemistry and PPARgamma levels
      were found to be upregulated 7 days after MPTP treatment. The importance of
      PPARgamma in protecting against MPTP toxicity was confirmed by treating C57BL6
      mice with GW9662. Treatment with GW9662 increased MPTP-induced neuronal loss in
      the SNpc whilst not affecting MPTP-induced reductions in striatal dopamine and
      3,4-dihdroxyphenylacetic acid. GW9662 also caused neuronal loss in the SNpc of
      saline-treated mice. The evidence presented here supports the role of anti
      oxidant mechanisms in the protective effects of PPARgamma agonists in
      neurodegenerative diseases, but indicates that these effects may be independent
      of PPARgamma activation. It also demonstrates the importance of PPARgamma
      activity for neuronal survival within the SNpc.

PMID- 22417925
TI  - Differential regulation of Nedd4 ubiquitin ligases and their adaptor protein
      Ndfip1 in a rat model of ischemic stroke.
AB  - Ubiquitin-modification of proteins by E3 ubiquitin ligases is an important post
      translational mechanism implicated in neuronal survival and injury following
      cerebral ischemia. However, of the 500 or so E3s thought to be present in
      mammalian cells, very few specific E3s have been identified and associated with
      brain ischemia. Here, we demonstrate endogenous induction of HECT-type E3 ligases
      of the Nedd4 family and their adaptor Nedd4-family interacting protein 1 (Ndfip1)
      following transient focal cerebral ischemia in rats. Ndfip1 is upregulated in
      surviving cortical neurons and its neuroprotective activity is correlated with
      Nedd4-2 upregulation, but not two other Nedd4 family members examined (Nedd4-1
      and Itch). Immunoprecipitation assays confirmed biochemical binding of Ndfip1
      with Nedd4-2 in the brain, with or without ischemic stroke, indicating their
      endogenous interaction. While Ndfip1 and Itch have been previously shown to
      interact outside of the nervous system, ischemic induction of Itch in the present
      study was associated with cellular survival independent of Ndfip1. Together,
      these findings demonstrate specific and differential regulation of Nedd4 family
      E3 ligases under ischemic conditions, and identify two E3 ligases and their
      adaptor that potentially regulate ubiquitination in ischemic stroke to provide
      neuroprotection.

PMID- 22417926
TI  - Schizophrenia comorbid with panic disorder: evidence for distinct cognitive
      profiles.
AB  - Patients with comorbid schizophrenia and panic symptoms share a distinct clinical
      presentation and biological characteristics, prompting some to propose panic
      psychosis as a separate subtype of schizophrenia. Less is known about these
      patients' neuropsychological profiles, knowledge of which may facilitate target
      specific treatments and research into the etiopathophysiology for such cases. A
      total of 255 schizophrenia patients with panic disorder (n=39), non-panic anxiety
      disorder (n=51), or no anxiety disorder (n=165) were assessed with the Wechsler
      Adult Intelligence Scale-Revised, the Wisconsin Card Sorting Test, the Trail
      Making Test, the Controlled Oral Word Association Test, the Animal Naming subtest
      of the Boston Diagnostic Aphasia Examination, and the Wechsler Memory Scale
      Revised. Psychotic symptoms were assessed with the Positive and Negative Syndrome
      Scale. Patients with panic disorder demonstrated a higher verbal IQ and better
      problem solving, set switching, delayed recall, attention, and verbal fluency as
      compared to schizophrenia patients without comorbid anxiety. The schizophrenia
      panic group reported a higher level of dysthymia on stable medication. Our
      findings suggest that patients with schizophrenia and comorbid panic disorder
      exhibit distinct cognitive functioning when compared to other schizophrenia
      patients. These data offer further support for a definable panic-psychosis
      subtype and suggest new etiological pathways for future research.

PMID- 22417927
TI  - "Looks do matter"--visual attentional biases in adolescent girls with eating
      disorders viewing body images.
AB  - Visual attention allocation of adolescent girls with and without an eating
      disorder while viewing body images of underweight, normal-weight and overweight
      women was studied using eye tracking. While all girls attended more to specific
      body parts (e.g. hips, upper legs), eating-disordered girls showed an attentional
      bias towards unclothed body parts.

PMID- 22417929
TI  - Stigmatising attitudes towards people with mental disorders: changes in Australia
      over 8 years.
AB  - The aim of the study was to investigate whether Australians' stigmatising
      attitudes towards people with mental disorders have changed over an 8-year
      period. In 2011, telephone interviews were carried out with 6019 Australians aged
      15 or over. The survey interview used the same questions as those of the 2003/4
      national mental health literacy survey, in which participants were presented with
      a case vignette describing either depression, depression with suicidal thoughts,
      early schizophrenia or chronic schizophrenia. Questions were asked about
      stigmatising attitudes, including personal and perceived stigma and social
      distance. Results showed decreases in social distance scores for all vignettes
      other than chronic schizophrenia and increases in beliefs about dangerousness and
      unpredictability. Campaigns to improve mental health literacy and reduce
      stigmatising attitudes may have had beneficial effects in reducing the desire for
      social distance from those with mental disorders. However, increase in beliefs
      about the dangerousness and unpredictability of those with these disorders is of
      concern and points to the need for public education to address these aspects of
      stigma.

PMID- 22417928
TI  - An examination of environmental and genetic contributions to the determinants of
      suicidal behavior among male twins.
AB  - The purpose of the present study was to examine the relative association of
      genetic and environmental factors with individual differences in each of the
      proximal, jointly necessary, and sufficient causes for suicidal behavior,
      according to the Interpersonal-Psychological Theory of Suicide (IPTS; Joiner,
      2005). We examined data on derived scales measuring acquired capability,
      belongingness, and burdensomeness (the determinants of suicidal behavior,
      according to theory) from 348 adolescent male twins. Univariate biometrical
      models were used to estimate the magnitude of additive genetic (A), non-additive
      genetic (D), shared environmental (C), and non-shared environmental (E) effects
      associated with the variance in acquired capability, belongingness, and
      burdensomeness. The best fitting model for the acquired capability allowed for
      additive genetic and environmental effects, whereas the best fitting model for
      burdensomeness and belongingness allowed for shared and non-shared environmental
      effects. The present research extends prior work by specifying the environmental
      and genetic contributions to the components of the IPTS, and our findings suggest
      that belongingness and burdensomeness may be more appropriate targets for
      clinical intervention than acquired capability as these factors may be more
      malleable or amenable to change.

PMID- 22417930
TI  - ECT stimulus dose dependence on current separately from charge.
AB  - Bilateral electroconvulsive therapy (ECT) seizure threshold charge averaged 162.8
      and 125.1 mC at 900 and 1150 mA, respectively (p<0.02), measured in randomized
      balanced order (N=18). Results are consistent with stimulus dose strongly
      depending on current besides charge, rather than charge alone. ECT stimuli of
      differing currents but equal charge differ in dose.

PMID- 22417931
TI  - Lower serum interleukin-2 levels in schizophrenic patients with tardive
      dyskinesia.
AB  - We determined serum interleukin-2 (IL-2) levels between schizophrenic patients
      with (n=45) and without tardive dyskinesia (TD; n=45) compared to normal controls
      (n=50). TD patients had lower serum IL-2 levels than non-TD patients, but higher
      IL-2 levels than normal controls. IL-2 was associated with the negative symptoms
      of schizophrenia, but not with TD severity. Immune disturbance may be involved in
      the pathophysiology of TD.

PMID- 22417932
TI  - Magical ideation, schizotypy and the impact of emotions.
AB  - Research indicates that emotions can interfere with basic cognitive functions
      such as attention and memory, and that schizotypal traits may be related to
      vulnerability to such interference, The schizotypal trait magical ideation,
      expressed as illogicality and tendencies to endorse peculiar or eccentric
      beliefs, has been reported to be related to impairments in social cognitive
      functioning as well risk for psychosis. This study examined the impact of
      emotionally arousing films on heart rate activity, affect ratings, and working
      memory. Participants were university students. Results indicated that high
      magical ideation scores were associated with impairments in short-term memory,
      higher post-film affect ratings, decreased clarity of affect awareness, and
      increased heart rate in response to emotionally arousing films. These results
      suggest that magical ideation may be an indicator of lower thresholds for arousal
      and increased vulnerability to disruption of cognitive processes by situations
      that elicit strong emotions.

PMID- 22417933
TI  - Variation in the catechol-O-methyltransferase (COMT) gene and treatment response
      to venlafaxine XR in generalized anxiety disorder.
AB  - Antidepressant drugs are the preferred choice for the treatment of generalized
      anxiety disorder (GAD). However, the choice of pharmacotherapy is determined on a
      trial-and-error basis, as the underlying mechanisms of treatment response are
      unknown. We examined whether the COMT gene, which has been known to play a role
      in antidepressant treatment response in major depressive disorder (MDD), has a
      pharmacogenetic effect in antidepressant treatment response in GAD. In our study,
      156 patients diagnosed with GAD received venlafaxine XR treatment as part of an
      18-month relapse prevention study. Genotypes were obtained for the COMT
      functional variant rs4680 (Val158Met) for all patients; however, pharmacogenetic
      analysis was only conducted for the European American population (n=112). We
      found no significant association between our primary Hamilton Anxiety Scale
      outcome measure and rs4680. However, we did find a nominally significant allelic
      association between this variant and a secondary treatment outcome measure (CGI
      I) in our European American population (n=112). Furthermore, we show a slight
      dominant effect of the A-allele with the CGI-I measure in the European American
      population indicating a possible pharmacogenetic role of rs4680 in antidepressant
      treatment outcome in GAD. Further studies in a larger population are needed to
      confirm this effect.

PMID- 22417934
TI  - Genome-wide association study identifies genetic loci associated with body mass
      index and high density lipoprotein-cholesterol levels during
      psychopharmacological treatment - a cross-sectional naturalistic study.
AB  - Metabolic and cardiovascular side effects are serious clinical problems related
      to psychopharmacological treatment, but the underlying mechanisms are mostly
      unknown. We performed a genome-wide association study of metabolic and
      cardiovascular risk factors during pharmacological therapy. Twelve indicators of
      metabolic side effects as well as cardiovascular risk factors were analyzed in a
      naturalistic sample of 594 patients of Norwegian ancestry. We analyzed
      interactions between gene variants and three categories of psychopharmacological
      agents based on their reported potential for side effects. For body mass index
      (BMI), two significantly associated loci were identified on 8q21.3. There were
      seven markers in one 30-kb region, and the strongest signal was rs7838490. In
      another locus 140kb away, six markers were significant, and rs6989402 obtained
      the strongest signal. Both of these loci are located upstream of the gene matrix
      metalloproteinase 16 (MMP16). For high density lipoprotein cholesterol (HDL-C),
      marker rs11615274 on 12q21 was significant. The results highlight three genomic
      regions potentially harboring susceptibility genes for drug-induced metabolic
      side effects, identifying MMP16 as a candidate gene. This deserves to be
      replicated in additional populations to provide more evidence for molecular
      genetic mechanisms of side effects during psychopharmacological treatment.

PMID- 22417935
TI  - The impact of familial risk for schizophrenia or bipolar disorder on cognitive
      control during episodic memory retrieval.
AB  - Episodic memory impairment is a robust correlate of familial risk for
      schizophrenia (SZ) and bipolar disorder (BD); still much is unknown about the
      processes that underlie this deficit and how they may be implicated in BD and SZ.
      We examined the possibility that (a) episodic memory impairment may arise from
      abnormalities in the cognitive control of interference between task-relevant and
      task-irrelevant memories during retrieval; inability to suppress task-irrelevant
      representations could give rise to intrusions of inappropriate memories and
      increased rate of forgetting, (b) cognitive control deficits during retrieval may
      be differentially affected by familial predisposition to SZ or BD. We examined
      episodic memory in relatives of patients with SZ (SZ-R) (n=15) or BD (BD-R)
      (n=17) compared to healthy controls (n=23) using the California Verbal Learning
      Test (CVLT) and the Doors and People Test (DPT). All relatives were free of any
      psychiatric morbidity and were matched to controls on age, sex, educational
      achievement and general intellectual ability. During the CVLT, both relatives'
      groups made significantly more perseverative recall errors than controls.
      However, intrusion errors were significantly increased in SZ-R only. SZ-R also
      showed increased rate of forgetting in the DPT while BD-R were comparable to
      controls. Familial predisposition to SZ, compared to that of BD, was associated
      with significantly greater impairment in cognitive control processes during
      episodic memory retrieval with some evidence of specificity for SZ in connection
      with mechanisms relating to increased forgetting.

PMID- 22417936
TI  - Increased risk of depressive disorder within 1 year after diagnosis with urinary
      calculi in Taiwan.
AB  - This study investigated the risk of subsequent depressive disorders (DD)
      following a diagnosis of urinary calculi (UC) in Taiwan. In total, 67,917 adult
      patients newly diagnosed with UC were recruited, along with 153,951 age-matched
      enrollees who were used as a comparison group. A stratified Cox proportional
      hazard regression analysis revealed that the adjusted hazard of DD within a 1
      year period following diagnosis with UC was 1.75 times greater for patients with
      UC than for comparison patients.

PMID- 22417937
TI  - Influence of parental consanguineous marriages on age at onset of bipolar
      disorder.
AB  - The present study was performed to investigate the association between parental
      consanguineous marriages and age at onset of bipolar disorder (BPD). A total of
      195 BPD patients participated in the study. Kaplan-Meier analysis revealed that
      relationships between age at onset and cumulative proportion of patients have
      different patterns with respect to types of parental marriages. Among early onset
      cases, the age at onset was higher for offspring of consanguineous than unrelated
      marriages, whereas in late onset cases the age at onset was lower for offspring
      of consanguineous than unrelated marriages. However, there was no difference
      between consanguineous and unrelated marriages for intermediate age at onset.

PMID- 22417938
TI  - Angio-oedema due to hereditary C1 inhibitor deficiency in children.
AB  - Hereditary angio-oedema due to C1 inhibitor deficiency (HAE-C1-INH) is a rare
      inherited disorder characterised by recurring and debilitating episodes of
      cutaneous swelling and abdominal pain and less frequent episodes of laryngeal
      oedema. Symptom onset is usually in childhood and early adolescence, with earlier
      disease onset associated with greater disease severity. Although HAE-C1-INH
      attacks are generally less frequent and less severe in children than in adults,
      they can cause significant physical and psychological impairment and affect
      advancement in school. There are often significant delays in the diagnosis of HAE
      C1-INH due to its variable clinical presentation and because abdominal symptoms
      can often mimic other common paediatric gastrointestinal disorders. In recent
      years, several disease-specific agents have become available for the acute and
      prophylactic treatment of HAE-C1-INH. Although these treatments have not been
      evaluated rigorously in controlled clinical trials in children with HAE-C1-INH,
      paediatric data on efficacy and safety are available for some agents. Early
      diagnosis and initiation of appropriate therapy in children with HAE-C1-INH can
      help reduce the burden of this illness in the paediatric population. 

PMID- 22417939
TI  - History of allergy is a predictor of adverse events in unstable angina treated
      with coronary angioplasty.
AB  - BACKGROUND: The aim was to investigate prognostic relevance of history of allergy
      in subjects with unstable angina treated with coronary angioplasty. METHODS:
      Fifty-seven consecutive patients with unstable angina who underwent coronary
      angioplasty were enrolled in the study and were divided into two groups: those
      with a history of allergy (Group A, N = 15); and controls (Group C, N =42). Major
      adverse cardiac events were recorded over a six-month follow-up period. Patients
      with primary or unsuccessful angioplasty and patients treated with drug eluting
      stent were excluded from the study. RESULTS: Group A patients (history of
      allergy) showed a 46.67% incidence of major adverse cardiac events at six-month
      follow-up (vs. 9.52% Group C, p < 0.01): results remained significant even in a
      multiple Cox regression analysis (hazard ratio 7.17, 95% CI 1.71-29.98, p <
      0.01). CONCLUSION: History of allergy is an independent predictor of major
      adverse cardiac events after coronary angioplasty in a six-month follow-up period
      in unstable angina.

PMID- 22417941
TI  - Regulation of motor circuit assembly by spatial and temporal mechanisms.
AB  - Precision of synaptic connections in neuronal circuits is the product of an
      orderly assembly process during development. Circuits controlling motor behavior
      have been studied extensively in many animal species, allowing an assessment of
      evolutionarily conserved organizational principles that underlie neuronal subtype
      specification, connectivity and function. Across phylogenetically distant
      species, motor circuit assembly is based on spatial organization of
      interconnected circuit elements. Developmental molecular coordinate systems
      demarcate dendritic and axonal targeting territories, thereby regulating
      convergence of synaptic partners. Additional mechanisms subsequently control fine
      synaptic connection specificity within these domains. Spatial organization often
      correlates with the orderly sequence of neurogenesis contributing to the
      generation of distinct postmitotic neuronal subpopulations, a developmental
      strategy implemented far beyond motor circuits.

PMID- 22417940
TI  - Novel mutator mutants of E. coli nrdAB ribonucleotide reductase: insight into
      allosteric regulation and control of mutation rates.
AB  - Ribonucleotide reductase (RNR) is the enzyme critically responsible for the
      production of the 5'-deoxynucleoside-triphosphates (dNTPs), the direct precursors
      for DNA synthesis. The dNTP levels are tightly controlled to permit high
      efficiency and fidelity of DNA synthesis. Much of this control occurs at the
      level of the RNR by feedback processes, but a detailed understanding of these
      mechanisms is still lacking. Using a genetic approach in the bacterium
      Escherichia coli, a paradigm for the class Ia RNRs, we isolated 23 novel RNR
      mutants displaying elevated mutation rates along with altered dNTP levels. The
      responsible amino-acid substitutions in RNR reside in three different regions:
      (i) the (d)ATP-binding activity domain, (ii) a novel region in the small subunit
      adjacent to the activity domain, and (iii) the dNTP-binding specificity site,
      several of which are associated with different dNTP pool alterations and
      different mutational outcomes. These mutants provide new insight into the precise
      mechanisms by which RNR is regulated and how dNTP pool disturbances resulting
      from defects in RNR can lead to increased mutation.

PMID- 22417942
TI  - Improved semiconductor lattice parameters and band gaps from a middle-range
      screened hybrid exchange functional.
AB  - We show  that the middle-range exchange-correlation hybrid of Henderson,
      Izmaylov, Scuseria and Savin (HISS) performs extremely well for elemental and
      binary semiconductors with narrow or visible spectrum band gaps, as well as some
      wider gap or more ionic systems used in devices. The lattice parameters are
      superior to those predicted by the screened hybrid functional of Heyd, Scuseria
      and Ernzerhof (HSE), and provide a significant improvement over the geometries
      predicted by typical semilocal functionals, yielding results competitive with
      PBEsol, which was specially tuned for solids. HISS also yields band gaps superior
      to those produced by functionals developed specifically for the solid state.
      Timings indicate that HISS is more computationally efficient than HSE, implying
      that the high quality lattice constants coupled with improved optical band gap
      predictions render HISS a useful adjunct to HSE in the modeling of geometry
      sensitive semiconductors.

PMID- 22417943
TI  - Tissue factor/factor VIIa complex: role of the membrane surface.
AB  - Blood clotting is triggered when the plasma serine protease factor VIIa binds to
      the cell-surface protein, tissue factor (TF); the resulting TF:FVIIa complex
      activates factors IX (FIX) and X (FX) by limited proteolysis. FVIIa, FIX and FX
      all bind reversibly to membranes via their gamma-carboxyglutamate-rich (GLA)
      domains, while TF is an integral membrane protein. Removing these proteases from
      the membrane surface is known to render them thousands of times less active,
      although the mechanisms by which blood clotting proteins bind to membranes-and
      the contributions of membranes to catalysis-remain very incompletely understood.
      Our recent and ongoing studies use a combination of nanoscale membrane bilayers
      (Nanodiscs), solid-state NMR and all-atom molecular dynamics (MD) simulations,
      enabling detailed insights into how GLA domains bind to phospholipid bilayers and
      how specific phospholipids enhance the catalytic activity of the TF:FVIIa
      complex.

PMID- 22417944
TI  - Tissue factor and factor VIIa--hemostasis and beyond.
AB  - Initiation of the coagulation cascade via exposure of active tissue factor (TF)
      to blood and formation of the factor VIIa/TF complex is essential for hemostasis
      and is an initial procoagulant signal in thrombosis. As of early 2012, over
      20,000 articles listed on PubMed describe advances in the understanding of TF
      biology in the settings of hemostasis and thrombosis, as well as in signaling
      events in cancer, sickle cell anemia, hyperlipidemia, and a broad spectrum of
      inflammatory disorders. It is both inspiring and humbling, then, to consider not
      only what has been learned about TF regulation, but also the number of questions
      still remaining about its role in physiology. This supplement reviews both well
      accepted and currently-controversial topics in coagulation and factor VIIa/TF
      biology, with particular foci on non-hemostatic roles of TF, innovative
      approaches for the treatment of hemophilia, and novel in vivo models of bleeding
      and thrombosis.

PMID- 22417945
TI  - The G894T polymorphism on endothelial nitric oxide synthase gene is associated
      with increased coronary heart disease among Asia population: evidence from a Meta
      analysis.
AB  - INTRODUCTION: Growing studies have revealed the underlying association between
      eNOS 894G/T (rs1799983) polymorphism and coronary heart disease (CHD) among Asia
      population. Results from these studies remained conflicting. We conducted this
      meta-analysis to estimate the overall CHD risk of eNOS 894G/T polymorphism
      regarding Asia population. MATERIALS AND METHODS: Up to October 2011, databases
      including PubMed, Embase and CNKI (China National Knowledge Infrastructure) were
      searched to access the relevant genetic association studies. Summary odds ratios
      and corresponding 95% confidence intervals (CIs) for eNOS 894G/T polymorphism and
      CHD risk were estimated using fixed or random-effects models when appropriate.
      RESULTS: 18 case-control studies with 2,994 cases and 3,130 controls were
      available for this study, including 13 studies of East-Asia descendents, 5
      studies of Non East-Asian descendents. The mean T allele frequency was 0.111 in
      the East-Asia population and 0.147 in the Non East-Asia population, respectively.
      The summary OR for CHD associated with the T allele was 1.52 (95% confidence
      intervals (95%CI), 1.37-1.69) by random effects model. Similarly, significantly
      increased risks were observed in the East-Asia population (OR=1.54; 95%CI=1.35
      1.76) and in the Non East-Asia population (OR=1.48; 95%CI=1.24-1.77),
      respectively. CONCLUSIONS: This meta-analysis indicated that eNOS 894G/T
      polymorphism may play an important role in CHD development among Asia population.

PMID- 22417947
TI  - Value of history taking in children and adolescents with cardiac syncope.
AB  - AIM: This study was designed to investigate the value of history taking in
      identifying children with cardiac syncope, and to improve diagnostic efficiency
      and accuracy in children with cardiac syncope. METHODS AND RESULTS: We compared
      the characteristics of a group of children and adolescents with cardiac syncope
      at the Pediatric Syncope Unit of five hospitals in China with those with typical
      vasovagal syncope. We included a cohort of 275 patients in Pediatric Syncope
      Unit. A cardiac cause of syncope was established in 31 patients, autonomic
      mediated reflex syncope in 214, non-syncopal attacks in 15, and in the remaining
      15 the cause of syncope remained unexplained. Cardiac syncope was triggered by
      exercise, whereas vasovagal syncope by prolonged standing, warm-crowded place,
      and fear or pain emotion. Syncopal spells occurred at various positions in
      cardiac syncope. Children who had prodromal symptoms with cardiac syncope were
      significantly fewer than those with vasovagal syncope. Most children with cardiac
      syncope had history of abnormal electrocardiogram findings when compared with
      children suffering from vasovagal syncope. On multivariable analysis, history of
      abnormal electrocardiogram findings and exercise-triggered syncope were
      independent predictors of cardiac syncope. CONCLUSION: Children and adolescents
      with a history of abnormal electrocardiogram findings and exercise-related
      syncope spells were at high risk for cardiac syncope.

PMID- 22417948
TI  - Should a rhythm check precede drug administration during cardiac arrest?

PMID- 22417946
TI  - Stress management skills, neuroimmune processes and fatigue levels in persons
      with chronic fatigue syndrome.
AB  - OBJECTIVES: Stressors and emotional distress responses impact chronic fatigue
      syndrome (CFS) symptoms, including fatigue. Having better stress management
      skills might mitigate fatigue by decreasing emotional distress. Because CFS
      patients comprise a heterogeneous population, we hypothesized that the role of
      stress management skills in decreasing fatigue may be most pronounced in the
      subgroup manifesting the greatest neuroimmune dysfunction. METHODS: In total, 117
      individuals with CFS provided blood and saliva samples, and self-report measures
      of emotional distress, perceived stress management skills (PSMS), and fatigue.
      Plasma interleukin-1-beta (IL-1beta, IL-2, IL-6, IL-10, and tumor necrosis factor
      alpha (TNF-alpha), and diurnal salivary cortisol were analyzed. We examined
      relations among PSMS, emotional distress, and fatigue in CFS patients who did and
      did not evidence neuroimmune abnormalities. RESULTS: Having greater PSMS related
      to less fatigue (p=.019) and emotional distress (p<.001), greater diurnal
      cortisol slope (p=.023) and lower IL-2 levels (p=.043). PSMS and emotional
      distress related to fatigue levels most strongly in CFS patients in the top
      tercile of IL-6, and emotional distress mediated the relationship between PSMS
      and fatigue most strongly in patients with the greatest circulating levels of IL
      6 and a greater inflammatory (IL-6):anti-inflammatory (IL-10) cytokine ratio.
      DISCUSSION: CFS patients having greater PSMS show less emotional distress and
      fatigue, and the influence of stress management skills on distress and fatigue
      appear greatest among patients who have elevated IL-6 levels. These findings
      support the need for research examining the impact of stress management
      interventions in subgroups of CFS patients showing neuroimmune dysfunction.

PMID- 22417949
TI  - Inhaling smoke causes smoke inhalation: put that in your hookah pipe!

PMID- 22417951
TI  - Temporal artery thermometer use in the prehospital setting.
AB  - OBJECTIVES: Prehospital vital signs are an important and required component of
      patient assessment. We compared the temporal artery thermometer (TAT) to the
      digital thermometer currently used in our emergency medical service (EMS) system
      and then to the digital thermometer used in the emergency department. The primary
      objective of this study was to assess the usefulness of the TAT in the
      prehospital setting. Other outcomes of interest included whether extraneous
      factors or cold ambient temperatures affected the TAT readings and paramedic
      satisfaction with the TAT. METHODS: This was a prospective, observational study.
      Patient temperature was taken by EMS personnel with both the digital thermometer
      and the TAT, and a chart review was conducted on a sample of these patients to
      compare the TAT to the emergency department digital thermometer. RESULTS: A total
      of 818 patients had their temperatures taken with both thermometers in the
      prehospital setting. The relationship between the TAT and digital thermometer
      measurement was positive and moderate; however, there was poor agreement between
      the two devices. Sixty-nine charts were reviewed, and a positive correlation was
      found between the TAT and the emergency department digital thermometer, with good
      agreement between the two devices. No extraneous factors were found to have a
      noticeable effect on the temperature measurements; the TAT performed well in cold
      weather, and the EMS personnel reported it to be easy to use. CONCLUSION: The TAT
      appears to be a suitable alternative to digital thermometers currently used in
      many EMS systems. The paramedics involved in this study liked the TAT better than
      the in-ambulance digital thermometer and believed it to be more accurate. Further
      research on this topic is required.

PMID- 22417952
TI  - Bedside emergency department ultrasonography availability and use for blunt
      abdominal trauma in Canadian pediatric centres.
AB  - OBJECTIVES: To quantify the current availability and use of bedside emergency
      department ultrasonography (EDUS) for blunt trauma at Canadian pediatric centres
      and to identify any perceived barriers to the use of bedside EDUS in such
      centres. METHODS: An electronic survey was sent to 162 pediatric emergency
      physicians and 12 site directors from the 12 pediatric emergency departments
      across Canada. RESULTS: Ninety-two percent (11 of 12) of centres completed the
      survey. The individual physician response rate was 65% (106 of 162), with 100% of
      site directors responding. Ultrasound machines were available in 45% (5 of 11) of
      centres. Forty-two percent (32 of 77) of emergency physicians working in equipped
      pediatric centres used bedside EDUS to evaluate blunt abdominal trauma (BAT). In
      the subgroup of staff who also worked at adults sites, the frequency of
      ultrasonography use for the evaluation of pediatric BAT was 75%. In the 55% (6 of
      11) of centres without ultrasonography, 88% of staff intend to incorporate its
      use in the future and 81% indicated that they believed the incorporation of
      ultrasonography would have a positive impact on patient care. The main perceived
      barriers to the use of ultrasonography in the evaluation of BAT were a lack of
      training (41%) and a lack of equipment (26%). CONCLUSION: Bedside EDUS is
      currently used in almost half of pediatric trauma centres, a frequency that is
      significantly lower than adult centres. Physicians in pediatric centres who use
      ultrasonography report that it has a high utility, and a great majority of
      physicians at pediatric centres without EDUS plan to incorporate it in the
      future. The main reported barriers to its use are a lack of training and a lack
      of equipment availability.

PMID- 22417953
TI  - How do we manage emergency department patients diagnosed with transient ischemic
      attack?
AB  - INTRODUCTION: Multiple studies have demonstrated low rates of antithrombotic use,
      low neuroimaging rates, and high subsequent risk of stroke at 90 days following
      an emergency department (ED) diagnosis of transient ischemic attack (TIA). This
      study assessed the use of antithrombotic medications, neuroimaging, and
      subsequent 90-day stroke rate for patients in a more recent cohort of ED patients
      discharged home with TIA. METHODS: We conducted a 1-year historical cohort study
      of all patients discharged with a TIA at a tertiary care ED (census 60,000
      visits/year), which was one of the four sites participating in one of the
      aforementioned studies. Data were extracted from paper and electronic records
      onto standardized data extraction forms. Clinical findings, medications, and
      tests were recorded. RESULTS: A total of 211 patients were enrolled in the study.
      The patients had the following characteristics: the mean age was 71.2 years (SD
      13.8 years), 56.9% were female, 53.1% had a history of hypertension, 26.5% had a
      history of ischemic heart disease, and 17.1% had a previous stroke. The most
      frequent neurologic deficit was unilateral weakness (53.6%), and most deficits
      lasted for more than 60 minutes (71.6%). Antithrombotic medications were used for
      96.7% of patients at ED discharge. Neuroimaging was conducted in 94.3% of
      patients while in the ED. Our cohort had a 90-day stroke rate of 1.9%.
      CONCLUSION: This study established that most TIA patients receive neuroimaging in
      the ED and are started on or maintained on antithrombotic agents. Clinicians are
      encouraged to ensure that electrocardiography is done routinely and to involve
      Neurology in follow-up care.

PMID- 22417954
TI  - Ontario children have outgrown the Broselow tape.
AB  - OBJECTIVE: The Broselow Pediatric Emergency Tape (Armstrong Medical Industries,
      Inc., Lincolnshire, IL) (BT) is a well-established length-based tool for
      estimation of body weight for children during resuscitation. In view of pandemic
      childhood obesity, the BT may no longer accurately estimate weight. We therefore
      studied the BT in children from Ontario in a large recent patient cohort.
      METHODS: Actual height and weight were obtained from an urban and a rural
      setting. Children were prospectively recruited between April 2007 and July 2008
      from the emergency department and outpatient clinics at the London Health Science
      Centre. Rural children from junior kindergarten to grade 4 were also recruited in
      the spring of 2008 from the Avon Maitland District School Board. Data for
      preschool children were obtained from three daycare centres and the electronic
      medical record from the Maitland Valley Medical Centre. The predicted weight from
      the BT was compared to the actual weight using Spearman rank correlation;
      agreement and percent error (PE) were also calculated. RESULTS: A total of 6,361
      children (46.2% female) were included in the study. The median age was 3.9 years
      (interquartile range [IQR] 1.56-7.67 years), weight was 17.2 kg (IQR 11.6-25.4
      kg), and height was 103.5 cm (IQR 82-124.4 cm). Although the BT weight estimate
      correlated with the actual weight (r  =  0.95577, p < 0.0001), the BT
      underestimated the actual weight by 1.62 kg (7.1% +/- 16.9% SD, 95% CI -26.0
      40.2). The BT had an >= 10% PE 43.7% of the time. CONCLUSIONS: Although the BT
      remains an effective method for estimating pediatric weight, it was not accurate
      and tended to underestimate the weight of Ontario children. Until more accurate
      measurement tools for emergency departments are developed, physicians should be
      aware of this discrepancy.

PMID- 22417955
TI  - How do I find a point-of-care answer to my clinical question?
AB  - Emergency physicians often need point-of-care access to current, valid
      information to guide patient management. Most emergency physicians do not work in
      a hospital with a computerized decision support system that prompts and provides
      them with information to answer their clinical questions. Searching for answers
      to clinical questions online, especially those related to diagnosis and
      treatment, can be challenging, in part because determining the validity and
      clinical applicability of the results of individual studies is beyond the time
      constraints of most emergency physicians. This article describes currently
      available point-of-care sources of evidence-based information to answer clinical
      questions and provides the access information for each.

PMID- 22417956
TI  - Canadian Association of Emergency Physicians sepsis treatment checklist:
      optimizing sepsis care in Canadian emergency departments.
AB  - OBJECTIVE: The Canadian Association of Emergency Physicians (CAEP) sepsis
      guidelines created by the CAEP Critical Care Practice Committee (C4) and
      published in the Canadian Journal of Emergency Medicine (CJEM) form the most
      definitive publication on Canadian emergency department (ED) sepsis care to date.
      Our intention was to identify which of the care items in this document are
      specifically necessary in the ED and then to provide these items in a tiered
      checklist that can be used by any Canadian ED practitioner. METHODS: Practice
      points from the CJEM sepsis publication were identified to create a practice
      point list. Members of C4 then used a Delphi technique consensus process over May
      to October 2009 via e-mail to create a tiered checklist of sepsis care items that
      can or could be completed in a Canadian ED when caring for the septic shock
      patient. This checklist was then assessed for use by a survey of ED practitioners
      from varying backgrounds (rural ED, community ED, tertiary ED) from July to
      October 2010. RESULTS: Twenty sepsis care items were identified in the CAEP
      sepsis guidelines. Fifteen items were felt to be necessary for ED care. Two
      levels of checklists were then created that can be used in a Canadian ED. Most ED
      physicians in community and tertiary care centres could complete all parts of the
      level I sepsis checklist. Rural centres often struggle with the ability to obtain
      lactate values and central venous access. Many items of the level II sepsis
      checklist could not be completed outside the tertiary care centre ED. CONCLUSION:
      Sepsis care continues to be an integral and major part of the ED domain. Practice
      points for sepsis care that require specialized monitoring and invasive
      techniques are often limited to larger tertiary care EDs and, although heavily
      emphasized by many medical bodies, cannot be reasonably expected in all centres.
      When the resources of a centre limit patient care, transfer may be required.

PMID- 22417958
TI  - Emergency department risk stratification in upper gastrointestinal bleeding.
AB  - CLINICAL QUESTION: What clinical features, compiled as a risk stratification
      tool, identify patients with upper gastrointestinal bleeding that can be safely
      managed and investigated in an outpatient setting? ARTICLE CHOSEN: Stanley AJ,
      Ashley D, Dalton HR. Outpatient management of patients with low-risk upper
      gastrointestinal hemorrhage: multicentre validation and prospective evaluation.
      Lancet 2009;373:42-7. OBJECTIVE: To validate the Glasgow-Blatchford Bleeding
      Score, a risk stratification tool for upper gastrointestinal bleeding.

PMID- 22417959
TI  - Surgical mask versus N95 respirator for preventing influenza among health care
      workers: a randomized trial.
AB  - CLINICAL QUESTION: Are surgical masks inferior to N95 respirators in reducing
      influenza infection in health care workers? ARTICLE CHOSEN: Loeb M, Dafoe N,
      Mahony J, et al. Surgical mask vs N95 respirator for preventing influenza among
      health care workers: a randomized trial. JAMA 2009;302:1865-71. OBJECTIVE: To
      evaluate the effectiveness of N95 respirators compared to standard surgical masks
      in reducing influenza infection in health care workers.

PMID- 22417960
TI  - The use of tranexamic acid for trauma patients?
AB  - CLINICAL QUESTION: Does giving tranexamic acid to trauma patients who are
      actively bleeding or at risk for significant hemorrhage have an impact on
      mortality? ARTICLE CHOSEN: CRASH-2 Trial Collaborators. Effects of tranexamic
      acid on death, vascular occlusive events, and blood transfusion in trauma
      patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled
      trial. Lancet 2010;376:23-32. OBJECTIVE: The study collaborators sought to
      evaluate the effect of tranexamic acid on mortality in trauma patients who were
      actively bleeding or at risk for significant hemorrhage. Secondary outcomes
      included the incidence of vascular occlusive events and the number of blood
      transfusions required.

PMID- 22417961
TI  - Carbon monoxide poisoning in narghile (water pipe) tobacco smokers.
AB  - Narghile (water pipe, hookah, shisha, goza, hubble bubble, argeela) is a
      traditional method of tobacco use. In recent years, its use has increased
      worldwide, especially among young people. Narghile smoking, compared to cigarette
      smoking, can result in more smoke exposure and greater levels of carbon monoxide
      (CO). We present an acutely confused adolescent patient who had CO poisoning
      after narghile tobacco smoking. She presented with syncope and a
      carboxyhemoglobin level of 24% and was treated with hyperbaric oxygen. Five
      additional cases of CO poisoning after narghile smoking were identified during a
      literature search, with carboxyhemoglobin levels of 20 to 30%. Each patient was
      treated with oxygen supplementation and did well clinically. In light of the
      increasing popularity of narghile smoking, young patients presenting with
      unexplained confusion or nonspecific neurologic symptoms should be asked
      specifically about this exposure, followed by carboxyhemoglobin measurement.

PMID- 22417962
TI  - A healing heart.

PMID- 22417963
TI  - My mentors.

PMID- 22417964
TI  - From Nova Scotia to Singapore: emergency medicine in action.

PMID- 22417965
TI  - Dexmedetomidine administration before, but not after, ischemia attenuates
      intestinal injury induced by intestinal ischemia-reperfusion in rats.
AB  - BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury is a devastating
      complication in the perioperative period. Dexmedetomidine is commonly applied in
      the perioperative period. The authors aimed to determine the effects of different
      doses of dexmedetomidine (given before or after intestinal ischemia) on
      intestinal I/R injury and to explore the underlying mechanisms. METHODS:
      Intestinal I/R injury was produced in rat by clamping the superior mesenteric
      artery for 1 h followed by 2 h reperfusion. Intravenous infusion of
      dexmedetomidine was performed at 2.5, 5, and 10 MUg . kg(-1) . h(-1) for 1 h
      before or after ischemic insult. In addition, yohimbine hydrochloride was
      administered intravenously to investigate the role of alpha2 adrenoreceptor in
      the intestinal protection conferred by dexmedetomidine. RESULTS: Intestinal I/R
      increased mortality of rats and caused notable intestinal injury, as evidenced by
      statistically significant increases in Chiu's scores; serum diamine oxidase and
      tumor necrosis factor-alpha concentration, accompanied by increases in the
      intestinal mucosal malondialdehyde concentration; myeloperoxidase activity; and
      epithelial cell apoptosis (all P < 0.05 vs. Sham). Except malondialdehyde and
      myeloperoxidase, all changes were improved by the administration of 5 MUg . kg(
      1) . h(-1) dexmedetomidine before ischemia (all P < 0.05 vs. Injury) but not
      after ischemia. Infusion of 2.5 MUg . kg(-1) . h(-1) dexmedetomidine before or
      after ischemia produced no beneficial effects, and infusion of 10 MUg . kg(-1) .
      h(-1) dexmedetomidine led to severe hemodynamic suppression. Yohimbine abolished
      the intestinal protective effect of the 5 MUg . kg(-1) . h(-1) dexmedetomidine
      infusion before ischemia and was accompanied by the disappearance of its
      antiapoptotic and antiinflammatory effect. CONCLUSION: Dexmedetomidine
      administration before, but not after, ischemia dose-dependently protects against
      I/R-induced intestinal injury, partly by inhibiting inflammatory response and
      intestinal mucosal epithelial apoptosis via alpha2 adrenoreceptor activation.

PMID- 22417966
TI  - Electroencephalographic recovery, hypnotic emergence, and the effects of
      metabolite after continuous infusions of a rapidly metabolized etomidate analog
      in rats.
AB  - BACKGROUND: Methoxycarbonyl etomidate is an ultrarapidly metabolized etomidate
      analog. It is metabolized to methoxycarbonyl etomidate carboxylic acid (MOC-ECA),
      which has a hypnotic potency that is 350-fold less than that of methoxycarbonyl
      etomidate. The authors explored the relationships between methoxycarbonyl
      etomidate infusion duration, recovery time, metabolite concentrations in blood
      and cerebrospinal fluid (CSF), and methoxycarbonyl etomidate metabolism in brain
      tissue and CSF to test the hypothesis that rapid metabolism of methoxycarbonyl
      etomidate may lead to sufficient accumulation of MOC-ECA in the brain to produce
      a pharmacologic effect. METHODS: A closed-loop system with burst suppression
      ratio feedback was used to administer methoxycarbonyl etomidate infusions of
      varying durations to rats. After infusion, recovery of the electroencephalogram
      and righting reflexes were assessed. MOC-ECA concentrations were measured in
      blood and CSF during and after methoxycarbonyl etomidate infusion, and the in
      vitro half-life of methoxycarbonyl etomidate was determined in rat brain tissue
      and CSF. RESULTS: Upon termination of continuous methoxycarbonyl etomidate
      infusions, the burst suppression ratio recovered in a biexponential manner with
      fast and slow components having time constants that differed by more than 100
      fold and amplitudes that varied inversely with infusion duration. MOC-ECA
      concentrations reached hypnotic concentrations in the CSF with prolonged
      methoxycarbonyl etomidate infusion and then decreased during a period of several
      hours after infusion termination. The metabolic half-life of methoxycarbonyl
      etomidate in brain tissue and CSF was 11 and 20 min, respectively. CONCLUSION: In
      rats, methoxycarbonyl etomidate metabolism is sufficiently fast to produce
      pharmacologically active MOC-ECA concentrations in the brain with prolonged
      methoxycarbonyl etomidate infusion.

PMID- 22417967
TI  - Gabapentin inhibits catecholamine release from adrenal chromaffin cells.
AB  - BACKGROUND: Gabapentin is most commonly prescribed for chronic pain, but acute
      perioperative effects, including preemptive analgesia and hemodynamic
      stabilization, have been reported. Adrenal chromaffin cells are a widely used
      model to investigate neurosecretion, and adrenal catecholamines play important
      physiologic roles and contribute to the acute stress response. However, the
      effects of gabapentin on adrenal catecholamine release have never been tested.
      METHODS: Primary cultures of bovine adrenal chromaffin cells were treated with
      gabapentin or vehicle for 18-24 h. The authors quantified catecholamine secretion
      from dishes of cells using high-performance liquid chromatography and resolved
      exocytosis of individual secretory vesicles from single cells using carbon fiber
      amperometry. Voltage-gated calcium channel currents were recorded using patch
      clamp electrophysiology and intracellular [Ca2+] using fluorescent imaging.
      RESULTS: Gabapentin produced statistically significant reductions in
      catecholamine secretion evoked by cholinergic agonists (24 +/- 3%, n = 12) or KCl
      (16 +/- 4%, n = 8) (mean +/- SEM) but did not inhibit Ca2+ entry or calcium
      channel currents. Amperometry (n = 51 cells) revealed that gabapentin inhibited
      the number of vesicles released upon stimulation, with no change in quantal size
      or kinetics of these unitary events. CONCLUSIONS: The authors show Ca2+ entry was
      not inhibited by gabapentin but was less effective at triggering vesicle fusion.
      The work also demonstrates that chromaffin cells are a useful model for
      additional investigation of the cellular mechanism(s) by which gabapentin
      controls neurosecretion. In addition, it identifies altered adrenal catecholamine
      release as a potential contributor to some of the beneficial perioperative
      effects of gabapentin.

PMID- 22417968
TI  - Exponential synchronization for reaction-diffusion networks with mixed delays in
      terms of p-norm via intermittent driving.
AB  - In this paper, the globally exponential synchronization for a class of reaction
      diffusion neural networks with Dirichlet boundary conditions and mixed delays is
      investigated based on periodically intermittent control. Some new and useful
      synchronization criteria in terms of p-norm are derived by introducing multi
      parameters, using Lyapunov functional theory. Subsequently, a feasible region of
      the control parameters for each neuron is derived for the realization of
      exponential synchronization. Besides, according to the theoretical results, the
      influences of diffusion strengths and diffusion spaces on synchronization are
      analyzed and a very interesting fact is revealed that the synchronization of
      neural networks with reaction-diffusions is more easily realized than those of
      neural networks without reaction-diffusions. Finally, a reaction-diffusion
      chaotic network is given to demonstrate the effectiveness of the proposed control
      methods.

PMID- 22417969
TI  - Isoflurane for life-threatening bronchospasm: a 15-year single-center experience.
AB  - BACKGROUND: Children with severe bronchospasm requiring mechanical ventilation
      may become refractory to conventional therapy. In these critically ill patients,
      isoflurane is an inhaled anesthetic agent available in some centers to treat
      bronchospasm. We hypothesized that isoflurane  is safe and would lead to improved
      gas exchange in children with life-threatening bronchospasm refractory to
      conventional therapy. METHODS: A retrospective review was conducted and included
      mechanically ventilated children treated with isoflurane in a quaternary
      pediatric ICU for life-threatening  bronchospasm, from 1993 to 2007. Demographic,
      blood gas, ventilator, and outcome data were collected. RESULTS: Thirty-one
      patients, with a mean age of 9.5 years (range 0.4-23 years) were treated with
      isoflurane, from 1993 to 2007. Mean time to initiation of isoflurane after
      intubation  was 13 hours (0-120 h), and the mean maximum isoflurane dose was 1.1%
      (0.3-2.5%). Mean duration of isoflurane administration was 54.5 hours (range 1
      181 h), with a total mean duration of mechanical ventilation of 252 hours (range
      16-1,444 h). Isoflurane led to significant  improvement in pH and P(CO(2)) within
      4 hours of initiation (P <= .001). Complications during isoflurane administration
      included hypotension requiring vasoactive infusions in 24 (77%), arrhythmia in 3
      (10%), neurologic side effects in 3 (10%), and pneumothorax in  1 (3%) patient.
      CONCLUSIONS: Isoflurane led to improvement in pH and P(CO(2)) within 4 hours in
      this series of mechanically ventilated patients with life-threatening
      bronchospasm. The majority of patients in this series developed hypotension, but
      there was a low incidence  of other side effects related to isoflurane
      administration. Isoflurane appears to be an effective therapy in patients with
      life-threatening bronchospasm refractory to conventional therapy. However,
      further investigation is warranted, given the uncertain overall impact of
      isoflurane in this  context.

PMID- 22417971
TI  - Direct loop-mediated isothermal amplification from Plasmodium chabaudi infected
      blood samples: inability to discriminate genomic and cDNA sequences.
AB  - Loop-mediated isothermal amplification (LAMP) has been increasingly used for
      diagnosis and quantification of pathogens. Since the Bst DNA polymerase used in
      this assay is highly resistant to PCR inhibitors present in blood, direct
      analysis of blood samples without DNA or RNA extraction is possible. Indeed, the
      presence of Plasmodium chabaudi specific nucleic acids was easily detectable
      using primer sets for P. chabaudi 18S rRNA and the cir 1 mRNA. Despite the fact
      that primers for cir 1, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and
      actin II mRNAs were used that spanned an intron, selective amplification of mRNA
      in the presence of contaminating genomic DNA was not possible. Optimization of
      the reaction temperature could only improve discrimination when low complexity
      templates (target sequences cloned in a plasmid vector) were used. Placing
      different LAMP primers across intron exon boundaries did not prevent
      amplification in the absence of reverse transcriptase. Probably due to the high
      A+T content and low number of introns only a very limited number of possible
      primer sets spanning introns could be identified in the target genes and no
      reaction conditions could be established that would allow quantification of RNA
      levels in the presence of DNA directly from blood samples.

PMID- 22417970
TI  - Pancreatic islet cell transplantation: an update for interventional radiologists.
AB  - Pancreatic islet cell transplantation is a promising cellular-based therapy for
      type 1 diabetes mellitus. This procedure involves portal venous injection of
      islet cells and affords 1-year insulin independence in as many as 80% of
      recipients. Although transplant surgeons represent historical drivers of islet
      therapy, requirement for image guidance and transcatheter techniques has fostered
      collaboration with interventional radiologists, who are positioned to play a
      significant role in clinical performance of islet transplantation and in basic
      science research in this field. This review article aims to familiarize
      interventional radiologists with islet cell transplantation patient selection,
      procedure technique, clinical outcomes, and future clinical and research avenues.

PMID- 22417972
TI  - In vitro amoebicidal activity of Origanum syriacum and Origanum laevigatum on
      Acanthamoeba castellanii cysts and trophozoites.
AB  - In some patients, complete treatment of amoebic keratitis is difficult because of
      the resistance of cysts to therapeutic agents. The aim of this study was to
      evaluate the in vitro amoebicidal activity of methanolic extracts of Origanum
      syriacum and Origanum laevigatum. In the presence of methanolic extracts (ranging
      from 1.0 to 32.0mg/ml), numbers of the viable Acanthamoeba castellanii
      trophozoites and cysts were decreased. Both extracts showed a time and dose
      dependent amoebicidal action on the trophozoites and cysts. Of the extracts
      tested, O. syriacum showed the stronger amoebicidal effect on the trophozoites
      and cysts. In the presence of 32 mg/ml extract, no viable trophozoites were
      observed within third hour. The extract was also found effective against the
      cysts within 24th hour. In the case of O. laevigatum, no viable trophozoites were
      observed within 72nd hour at the concentrations of 16 and 32 mg/ml. As expected,
      cysts were found more resistant to the extracts than the trophozoites.

PMID- 22417973
TI  - Theory and simulation: complexity and emergence.

PMID- 22417974
TI  - The expression of iNOS and nitrotyrosine in colitis and colon cancer in humans.
AB  - Chronic inflammation increases the risk of development of several types of
      malignancies including colon cancer. It also represents a paradigm for the
      connection between inflammation and cancer in terms of epidemiology and
      mechanistic studies in preclinical models. A key component of inflammation
      promoting cancer is the transcription factor NF-kappaB, which is known to play a
      critical role in the regulation of the inducible nitric oxide synthase (iNOS)
      gene. iNOS is an enzyme dominantly expressed during inflammatory reactions.
      Although synthesis of high amounts of nitric oxide (NO) by iNOS has been
      demonstrated in pathophysiological processes, such as acute or chronic
      inflammation and tumorigenesis, the role of iNOS activity in these diseases is
      still not well understood. Analysis of human biopsies of colitis and colon cancer
      using immunohistochemistry revealed elevated iNOS protein expression levels,
      which were strongly paralleled by increased expression of nitrotyrosine
      suggesting that iNOS has been highly activated in these tissues. These results
      were corroborated in an in vitro study showing the presence of high iNOS levels
      in a colon cancer cell line (HT-29) following inflammatory stimuli (TNF-alpha,
      peroxynitrite). In addition, the involvement of metastatic processes in the colon
      biopsies was assessed by means of in situ zymography of MMP activation. MMP 2
      (gelatinase A) activation was higher in histopathological sections of colitis and
      cancer compared to controls. Overall, these data strengthen the findings that in
      inflammation and colon cancer in humans, iNOS expression and tyrosine nitration
      may be an indicator of cancer development and progression.

PMID- 22417975
TI  - 3D simulation of the aqueous flow in the human eye.
AB  - Glaucoma results in an increase in the resistance of the aqueous humor outflow,
      which in turn leads to an increase of the intraocular pressure (IOP). Several
      treatments are proposed to reduce and stabilize the IOP that include medications,
      filtering surgery and glaucoma drainage devices (GDD). So far computational fluid
      dynamics (CFD) modeling of the eye drainage system has not yet been well studied.
      Therefore our goal was to provide a 3D CFD model of the eye based on the anatomy
      of a real human eye. Such a tool would serve for future evaluation of new
      glaucoma surgical techniques involving, for example, GDD. The model was based on
      stacks of microphotographs from human eye slides from which digital processing of
      the images of the eye structure and 3D reconstruction of the model were
      performed. Simulations of the distribution of pressure and flow velocity in the
      model of a healthy eye gave results comparable to physiology references.
      Mimicking glaucoma conditions led to an increase of the IOP from normal range,
      which went down to lower values after a filtering procedure. Further refinements
      in the boundary conditions for the filtering procedure shall improve the accuracy
      of this innovative tool for modeling glaucoma surgery.

PMID- 22417976
TI  - A method for characterizing stapes prostheses by their mechanical transfer
      function.
AB  - In this contribution, we present and evaluate a method for characterizing stapes
      prostheses by their mechanical transfer function. The measurements were carried
      out after a stapedotomy surgery was performed in three human temporal bones
      conserved in 4% formaldehyde. The inner ear was drained of fluid. Successively,
      one of three different stapes prostheses was inserted. After such preparation,
      the prosthesis piston movement compared to the incus movement is measured with
      laser vibrometry. The magnitude transfer function considered is defined as the
      amplitude of the prosthesis piston movement compared to the amplitude of the
      incus movement. Measurements were made in a frequency range from 500Hz to 4kHz.
      The measured amplitudes roughly ranged between 10nm and 100nm. A great advantage
      of the presented method is the fact that only a small portion of the ossicular
      chain influences the measurement, mainly the joint between the prosthesis and the
      incus. Furthermore, the usage of cadaver temporal bones allows for an automated
      measurement setup, long term experiments and the access of measurement positions
      inapproachable during in vivo measurements. With this method, the different kinds
      of prostheses could be evaluated on incuses of different diameters.

PMID- 22417977
TI  - Detection of the electrocardiogram fiducial points in the phase space using the
      Euclidian distance measure.
AB  - The paper proposes a phase-space based algorithm applying the Euclidian distance
      measure enabling detection of heartbeats and characteristic (fiducial) points
      from a single-lead electrocardiogram (ECG) signal. It extends the QRS detection
      in the phase space by detecting the P and T fiducial points. The algorithm is
      derived by reconstructing the ECG signals in a two-dimensional (2D) phase space
      according to the delay method and utilizes geometrical properties of the
      reconstructed phase portrait of the signal in the phase space for the heartbeat
      and fiducial-point detection. It uses adaptive thresholding and the Euclidian
      distance measure between the signal points in the phase portrait as an
      alternative to the phase-portrait area calculation (Lee et al., 2002). It was
      verified with the QT Database (2011) and its performance was assessed using
      sensitivity (Se) and the positive predictive value (PPV). Results for the
      proposed algorithm are 99.06%, 99.75% and 99.66% for Se and 94.87%, 99.75% and
      99.66% for PPV for the P points, heartbeats and T points, respectively.

PMID- 22417978
TI  - Technical variability of the GT3X accelerometer.
AB  - To analyze the intra- and inter-instrument reliability of the ActiGraph GT3X
      accelerometer using a vibration table on each orthogonal axis and at five
      frequencies of motion. Ten GT3X units were subjected to a specific vibration
      using a motorized vibration table along the vertical, horizontal right-left and
      horizontal front-back axis, and at 1.1, 2.1, 3.1, 4.1 and 10.2 Hz. The 5 min data
      for each frequency were analyzed separately for frequency, axis effects, and
      inter- and intra-instrument variability. We found overall high intra-and inter
      instrument reliability for the GT3X accelerometer at frequencies between 2.1 and
      4.1 Hz. For frequencies ranging between 2.1 and 4.1 Hz, the intra-instrument
      coefficient of variation was <=2.5%. The inter-instrument coefficient of
      variation ranged widely along axes and frequencies, with the lowest values (<=9%)
      corresponding to 2.1-4.1 Hz. The intra-class correlation coefficient for activity
      counts across frequencies and for all axes was 0.97. Overall, our findings
      support the use of the GT3X accelerometer as an accurate tool to estimate free
      living physical activity, at least within those frequencies that are common to
      most types of human daily activities.

PMID- 22417979
TI  - High quality p-type Ag-doped ZnO thin films achieved under elevated growth
      temperatures.
AB  - By correlating the effects of substrate temperature, oxygen pressure and laser
      energy on the electrical and microstructural properties of Ag-doped ZnO films
      grown on a sapphire (0001) substrate, p-type conductivity is achieved under
      various substrate temperatures in the wide range of 250-750  degrees C. All of
      the samples were deposited by pulsed-laser deposition under various designed
      conditions. Hall measurements indicate that the best conductivity is achieved in
      Ag-ZnO films under a substrate temperature of 500  degrees C, a partial oxygen
      pressure of 250-300 mTorr and laser energy between 330 and 345 mJ. The hole
      carrier concentration is 2.29 * 10(18) cm(-3), the resistivity is 0.9 Omega cm
      and the mobility is 3.03 cm(2) V(-1) s(-1). Transmission-electron microscopy
      (TEM) studies on the p-type films reveal similar microstructural properties to
      one another, but different properties to that of the n-type films deposited at
      the same temperatures with different deposition parameters.

PMID- 22417980
TI  - No increased mortality risk in older persons with unexplained anaemia.
AB  - BACKGROUND: in older persons, anaemia is associated with a number of unfavourable
      outcomes. In approximately 30% of older persons with anaemia, the cause of the
      anaemia is unexplained. We assessed the clinical differences between subjects
      with explained and unexplained anaemia and investigated whether these subjects
      have different mortality patterns compared with subjects without anaemia. DESIGN:
      observational prospective follow-up study. SETTING: the Leiden 85-plus study.
      PARTICIPANTS: four hundred and ninety-one persons aged 86 years. METHODS: the
      study population was divided in three groups: (i) no anaemia (reference group,
      n=377), (ii) explained anaemia (iron deficiency, folate deficiency, vitamin B12
      deficiency, signs of myelodysplastic syndrome or renal failure, n=74) and (iii)
      unexplained anaemia, (n=40). Mortality risks were estimated with Cox-proportional
      hazard models. RESULTS: haemoglobin levels were significantly lower in subjects
      with explained anaemia than in subjects with unexplained anaemia (P<0.01). An
      increased risk for mortality was observed in subjects with explained anaemia [HR:
      1.93 (95% CI: 1.47-2.52), P<0.001], but not in subjects with unexplained anaemia
      [HR: 1.19 (95% CI: 0.85-1.69), P=0.31]. Adjusted analyses (sex, co-morbidity,
      MMSE, institutionalised and smoking) did not change the observed associations for
      both explained and unexplained anaemic subjects. CONCLUSION: older subjects with
      unexplained anaemia had similar survival compared with non-anaemic subjects.
      Increased mortality risks were observed in subjects with explained anaemia
      compared with non-anaemic subjects.

PMID- 22417981
TI  - A review of vertebroplasty for osteoporotic and malignant vertebral compression
      fractures.
AB  - Vertebral compression fractures are a common clinical problem and the incidence
      of them will increase with the ageing population. Traditionally management has
      been conservative; however, there has been a growing trend towards vertebroplasty
      as an alternative therapy in patients with persisting severe pain. NICE produced
      guidance in 2003 recommending the procedure after 4 weeks of conservative
      management. Recent high-quality studies have been contradictory and there is
      currently a debate surrounding the role of the procedure with no agreement in the
      literature. We examine the evidence in both osteoporotic and malignant vertebral
      compression fractures; we also describe the benefits and side effects,
      alternative treatment options and the cost of the procedure. Finally, we
      recommend when vertebroplasty is most appropriately used based on the best
      available evidence.

PMID- 22417982
TI  - 'Not another UTI ... '.
AB  - Malaria includes a global disease burden with approximately 300-500 million cases
      worldwide annually. Varied symptomatology creates a diagnostic challenge. This is
      a case report of a stroke rehabilitation facility resident who developed
      Plasmodium ovale infection, several months post-exposure. Physicians should
      maintain a broad list of differential diagnoses, thinking beyond the range of
      common diagnoses.

PMID- 22417983
TI  - Lower extremity muscle quality and gait variability in older adults.
AB  - BACKGROUND: it is not clear if gait variability is linked to muscle strength or
      muscle quality (MQ). This study examined the relation between leg strength and
      lower extremity MQ and gait variability in healthy ambulatory older adults.
      METHODS: seventy-two older adults (43 females and 29 males; age: 69.5 +/- 6.1
      years) underwent assessments of gait, leg strength and body composition. Leg
      strength was assessed with an isokinetic dynamometer and body composition by dual
      energy X-ray absorptiometry (DXA). MQ was calculated from the information muscle
      strength and body composition. Gait was assessed by having the subjects walk down
      a pressure sensitive walkway at self-selected normal speed. Variability of
      spatial and temporal parameters of gait was calculated. RESULTS: there were
      minimal correlations between muscle strength and spatial parameters. However,
      both lower leg and upper leg MQ were negatively associated with spatial (r's = 
      0.24 to -0.49, P < 0.05) and temporal gait variability (r's = -0.27 to -0.35, P <
      0.05). Also, lower leg MQ was found to be a better predictor of gait variability
      than upper leg MQ. CONCLUSIONS: the results highlight that MQ may be an important
      determinant of gait function, even in healthy older adults.

PMID- 22417984
TI  - High-sensitivity C-reactive protein and mobility disability in older adults.
AB  - OBJECTIVE: to determine the association of high sensitivity C-reactive protein
      (HsCRP) levels with a risk of mobility disability and decline in older adults
      with and without vascular disease. DESIGN: prospective cohort. SETTING: community
      residing population. SUBJECTS: six hundred and twenty-four adults age 70 and
      older (62% women) with gait and HsCRP assessments. MAIN OUTCOME MEASURES:
      incident mobility disability (velocity <70 cm/s) and annual rates of decline on
      gait velocity. RESULTS: elevated HsCRP levels (>= 3 mg/l) at baseline present in
      224 of the 624 eligible subjects was associated with a faster annual decline in
      gait velocity of 0.91 cm/s (P=0.02). Subjects with elevated HsCRP levels had
      increased risk of mobility disability (hazard ratio: 1.85, 95% CI: 1.09-3.14).
      Each one-unit increase in log HsCRP levels in the 406 subjects without prevalent
      mobility disability was associated with increased risk of mobility disability
      (hazard ratio: 1.33, 95% CI: 1.05-1.68). The association of baseline HsCRP levels
      with mobility disability and decline was stronger in the 224 individuals without
      vascular disease. The associations were not significant in the 400 subjects with
      vascular disease. CONCLUSIONS: HsCRP levels predict mobility disability and
      accelerated decline in walking speed in older adults. These associations were
      stronger in those without vascular disease.

PMID- 22417985
TI  - Analysis of pitch range after arytenoid adduction by fenestration approach
      combined with type I thyroplasty for unilateral vocal fold paralysis.
AB  - OBJECTIVE: The purpose of this study was to determine the postoperative pitch
      range acquired in cases of unilateral vocal fold paralysis, as well as factors
      affecting outcomes. SUBJECTS AND METHODS: We analyzed 39 cases of unilateral
      vocal fold paralysis for which surgery was performed between January 2006 and
      January 2009 and for which pitch ranges and the items listed below were measured
      preoperatively and 1 year postoperatively. Arytenoid adduction (AA) and type I
      thyroplasty were performed simultaneously in all cases regardless of preoperative
      severity. AA was performed by the fenestration approach as previously reported.
      In this procedure, the cricoarytenoid and cricothyroid joints are not released.
      Correlations between pitch range acquired postoperatively and the following items
      were examined: (1) pre- and postoperative maximum phonation time (MPT), (2) pre-
      and postoperative mean airflow rate (MFR), and (3) preoperative pitch range.
      Furthermore, patients were surveyed regarding their ability to sing after
      surgery, and the pitch range cutoff value dividing ability and inability to sing
      was calculated. RESULTS: Pitch range increased significantly from 3+/-4.47
      halftones (mean +/- standard deviation) preoperatively to 17.5+/-5.80 halftones
      postoperatively. Preoperative MPT, MFR, and pitch range did not correlate with
      postoperative pitch range. Postoperatively, only MPT correlated with the width of
      postoperative pitch range. Twenty-three of 39 subjects (59%) responded that they
      were able to sing, and the pitch range cutoff value dividing the two groups was
      22 halftones. CONCLUSION: AA and type I thyroplasty significantly expanded
      postoperative pitch range. There was no correlation between preoperative severity
      and width of pitch range acquired postoperatively.

PMID- 22417986
TI  - Development of a novel live vaccine delivering enterotoxigenic Escherichia coli
      fimbrial antigens to prevent post-weaning diarrhea in piglets.
AB  - The efficacy of a novel, live delivery vaccine was examined for protection
      against post-weaning diarrhea in pigs. An expression/secretion plasmid harboring
      genes encoding enterotoxigenic Escherichia coli K88ab, K88ac, FedA and FedF
      fimbriae was constructed and harbored in an attenuated Salmonella, which was used
      as the vaccine candidate. Groups A (n=3) and B (n=3) sows were orally immunized
      with the candidate vaccine and PBS as a control, respectively, at 8 and 11 weeks
      of pregnancy. All group piglets were challenged with two challenge strains at 5
      week-old. All immunized sows had significantly increased IgG and IgA levels in
      both serum and colostrum to individual adhesins compared to the control (p <=
      0.05). Immune response in Group A piglets were significantly increased (p <=
      0.05). Furthermore, no clinical signs were observed in Group A piglets after the
      challenge and no challenge strains were detected in rectal swabs, while diarrhea
      was observed in 47.8% control piglets and challenge strains were isolated from
      all the diarrheic piglets. These results show that immune response of sucking
      piglets can maintain at higher levels through the milk of the immunized sows and
      vaccination of sows with the candidate may protect colibacillosis in weaned
      piglets.

PMID- 22417987
TI  - An untapped, untanned market.

PMID- 22417989
TI  - Quality assurance in postgraduate medical education: implications for dermatology
      residency training programs.
AB  - BACKGROUND: In the past few years, quality assurance has become an increasingly
      important part of medical education for both Canadian and American training
      programs. Since this emphasis on quality assurance in residency programs is
      recent, most faculty members involved in teaching residents in dermatology
      training programs would not themselves have had experience with quality
      assurance. As a result, satisfying this requirement may be a challenge.
      OBJECTIVES: In this article, we review published reports in which various
      residency training programs have satisfied this requirement and propose projects
      in which dermatology residency training programs may satisfy quality assurance
      requirements. METHODS: Using the key words residency, training, project, quality,
      assurance, improvement, medical errors, and safety, a literature search was
      conducted of English-language articles published after January 1990.
      RESULTS/CONCLUSIONS: There are many innovative and effective ways program
      directors in dermatology training programs should be able to develop projects
      that improve patient care, enhance resident education, and fulfill accreditation
      requirements.

PMID- 22417990
TI  - Purse-string suture for round and oval defects: a useful technique in
      dermatologic surgery.
AB  - BACKGROUND: Round and oval skin wounds, like facial pigmented nevi after
      excision, are traditionally sutured linearly for closure, leaving significant
      scars, which greatly influences their appearance. OBJECTIVE: This article
      provides an overview of our experience using intradermal purse-string suture for
      round and oval defects in the faciocervical region to ascertain whether purse
      string suture closure for such defects can result in good functional and cosmetic
      outcomes. METHODS AND RESULTS: We present 63 cases with different skin lesions in
      the faciocervical area. The defects of the lesions after excision were closed
      using intradermal purse-string suture. The wounds showed good final healing
      without obvious adverse events postoperatively. The result of scar assessment
      using the Vancouver Scar Scale was satisfying, with a total score of only 1.11.
      The final cosmetic appearance of the healed wounds seemed to be excellent and
      acceptable as they were always smaller than the original defects, with minimal
      scarring. CONCLUSION: Purse-string suture enabled us to repair small, circular
      wounds easily after excision of skin lesions. It is an excellent alternative to
      other reconstructions and a rapid, simple method to close skin defects with
      minimal scarring, achieving an excellent long-term cosmetic and functional
      outcome.

PMID- 22417991
TI  - Comparative study of IQ-ultra and Finn Chambers test methodologies in detecting
      10 common standard allergens that cause allergic contact dermatitis.
AB  - BACKGROUND: Patch testing is routinely used in contact dermatitis clinics because
      it is the gold standard for the evaluation of potential allergic contact
      dermatitis. OBJECTIVE: The study was undertaken to evaluate possible differences
      in reactivity between the Finn Chamber and IQ-Ultra patch-testing methodologies.
      METHODS: Patients were patch-tested simultaneously with the Finn Chamber and IQ
      Ultra patch tests. Ten standard allergens set by the North American Contact
      Dermatitis Group were used for both techniques. RESULTS: Both patch tests had a
      significant agreement in detecting all of the allergens. An "almost perfect
      agreement" was noted for ethylenediamine dihydrochloride, quaternium-15, mercapto
      mix, black rubber mix, balsam of Peru, and nickel sulfate; "substantial
      agreement" for formaldehyde, bisphenol A epoxy resin, and 4-tert-butylphenol
      formaldehyde resin; and "moderate agreement" for potassium dichromate.
      CONCLUSION: The Finn Chamber and IQ-Ultra patch tests had a good agreement in the
      detection of the 10 standard allergens that were tested.

PMID- 22417992
TI  - Pathway to dry skin prevention and treatment.
AB  - BACKGROUND: This article presents an evidence-supported clinical pathway for dry
      skin prevention and treatment. OBJECTIVE: The development of the pathway involved
      the following: a literature review was conducted and demonstrated that literature
      on dry skin is scarce. To compensate for the gap in the available literature, a
      modified Delphi method was used to collect information on prevention and
      treatment practice through a panel, which included 10 selected dermatologists who
      currently provide medical care for dermatology patients in Ontario. An advisor
      experienced in this therapeutic area guided the process, including a central
      meeting. Panel members completed a questionnaire regarding their individual
      practice in caring for these patients and responded to questions on assessment of
      dry skin etiology, frequency of skin care visits for consultation and follow-up,
      assessment, and referral to other specialties. The panel members reviewed a
      summary of all responses and reached a consensus. The result was presented as a
      clinical pathway. CONCLUSION: The panel concluded that our current awareness of
      dry skin and therefore prevention and effective treatment is limited; that
      identifying dry skin and its clinical issues requires tools such as clinical
      pathways, which may improve patient outcomes; and that additional research on dry
      skin etiology, prevention, and treatment is necessary.

PMID- 22417993
TI  - Demographic and tumor characteristics of patients diagnosed with nonmelanoma skin
      cancer: 13-year retrospective study.
AB  - BACKGROUND: The incidence of basal cell carcinoma (BCC) and squamous cell
      carcinoma (SCC) is increasing worldwide; however, this varies by region. To date,
      there are limited data about trends of nonmelanoma skin cancer (NMSC) in Canada.
      OBJECTIVE: To determine the demographic and tumor characteristic changes in
      patients diagnosed with BCC and SCC from 1993 to 2005 in a dermatology practice
      in Vancouver, British Columbia. METHOD: A retrospective chart review was
      conducted on patients with biopsy-confirmed NMSC between 1993 and 2005.
      Demographic and tumor characteristics were documented for the first two incident
      BCCs and SCCs per patient, and a descriptive data analysis was undertaken.
      RESULTS: A total of 1,177 NMSCs were identified from 885 patient charts. The
      number of BCCs increased from 1993 to 2003 and then decreased until 2005. BCCs
      and SCCs were generally diagnosed in older people (60+ years); however, an
      important group of younger patients (20-39 years) was also diagnosed with BCCs.
      BCCs and SCCs were most commonly seen on the head and neck, but the leg was a
      common location for SCC in women. CONCLUSION: NMSC is prevalent in British
      Columbia. These results highlight the fact that NMSC can affect individuals
      younger than 40 years old. Prevention strategies are warranted to reduce the
      burden of NMSC in British Columbia.

PMID- 22417994
TI  - Local side effects caused by hair dye use in females: cross-sectional survey.
AB  - BACKGROUND: Despite its association with a number of side effects, hair dye use
      is common worldwide. OBJECTIVE: To explore the local side effects of hair dye use
      and to relate these effects to features of hair dyeing. METHODS: A questionnaire
      about hair dye use was distributed to a random sample of 650 female patients at
      various outpatient clinics in 2008. RESULTS: A total of 567 females returned the
      questionnaire (87.2% response rate). Of these respondents, 82.6% (464 of 562) had
      used hair dye products in the past. The mean age at first use was 22.23 +/- 7.05
      years, and the median time between two consecutive dyes was 6 months. Of these
      respondents, 76.8% (354 of 461) used permanent dyes. Participants reported that
      they suffered skin redness caused by hair dyes (15.1%, 65 of 431), had scaling
      (14.4%, 60 of 417), or had itchiness (31.3%, 134 of 428). In addition, 74% (262
      of 354) of the participants reported that they had issues with the texture or
      condition of hair following hair dye use; 77.7% (314 of 404) reported split ends,
      whereas 69.6% (273 of 392) reported hair dryness, 69.4% (256 of 369) lusterless
      hair, 77.2% (308 of 399) excessive hair loss, and 53.6% (210 of 392) excessive
      hair graying. Furthermore, 55.1% (196 of 356) of the participants reported a
      slowing of hair growth. The total number of hair dyeing events was associated
      with increased hair loss (p  =  .04) and excessive graying (p < .001) after
      controlling for all relevant variables. CONCLUSION: Hair dye is associated with
      local side effects to the skin and hair. Increased public awareness of these
      risks could help inform consumer choices and reduce excessive use.

PMID- 22417995
TI  - Langerhans cell histiocytosis.
AB  - BACKGROUND: The cutaneous presentation of Langerhans cell histiocytosis (LCH) is
      very rare and can be highly variable among individuals, which can often lead to a
      delay in diagnosis. OBJECTIVE: To discuss a case report and literature review of
      important clinical indicators, histology, diagnosis, evaluation, and treatment
      guidelines. METHODS: Case report and literature review. RESULTS: Skin biopsies
      positive for CD1a and/or langerin are diagnostic for LCH. A thorough review of
      systems, baseline laboratory tests, and imaging studies can determine the extent
      of LCH. Treatment of cutaneous disease is largely based on case report and small
      case studies, but baseline treatment should generally begin with oral or topical
      steroids. When patients have more severe disease that requires a systemic
      approach, the efficacy of therapy should be assessed 6 weeks into therapy, with
      subsequent treatment intensification in patients with limited response.
      CONCLUSION: Owing to the rarity of this condition, there are no specific
      guidelines for treatment of LCH, but guidelines put forth by the Histiocyte
      Society assist in categorization and basic treatment approaches for patients with
      systemic disease.

PMID- 22417996
TI  - Mycophenolate mofetil and erythromycin for bullous lupus erythematosus of
      childhood.
AB  - BACKGROUND: Bullous lupus erythematosus is a rare disease that is extremely rare
      in childhood (with only seven previous reports) and difficult to control.
      OBJECTIVE: Herein is presented the youngest patient reported with this condition,
      and a novel, safe, and effective treatment regimen is described. METHODS: Through
      study, perseverance, serendipity, and creativity, a safe and effective regimen
      was developed. RESULTS: The combination of mycophenolate mofetil and erythromycin
      (plus sun protection) was found to be efficacious. CONCLUSION: It is proposed
      that the two medications act synergistically, with the "antibiotic" acting as a
      antiinflammatory agent, but at a different point in the inflammatory cascade than
      mycophenolate mofetil. This suggests the approach of using common, inexpensive,
      and benign antibiotics to potentiate, and perhaps decrease the use of,
      immunomodulatory agents in autoimmune and autoinflammatory diseases.

PMID- 22417997
TI  - Intracranial spread of Merkel cell carcinoma to the cerebellopontine angle.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a rare, highly malignant, and
      aggressive dermal neuroendocrine neoplasm that rarely metastasizes to the central
      nervous system. OBJECTIVE: To review the current literature regarding treatment
      of neurometastatic MCC. METHODS: A case of a 78-year-old male with intracranial
      extra-axial metastatic MCC involving the left cerebellopontine angle is
      presented. RESULTS: A retrosigmoid craniectomy was performed with complete
      resection of the metastatic focus. Adjuvant treatment included whole-brain
      radiation therapy followed by etoposide and carboplatin chemotherapy. Seven
      months postoperatively, the patient was free of metastatic disease. CONCLUSION:
      Surgical resection should be performed when feasible to prevent local recurrence.
      This may be followed by early adjuvant fractionated whole-brain radiotherapy and
      systemic chemotherapy; however, no clinical trials have been performed to
      demonstrate a survival benefit.

PMID- 22417998
TI  - Figurate erythema: an unusual presentation of the nonbullous phase of bullous
      pemphigoid.
AB  - BACKGROUND AND OBJECTIVE: Bullous pemphigoid, an autoimmune disorder, most
      commonly presents as a bullous eruption in patients over the age of 60. There may
      be a prodromal urticarial or papular eruption that evolves to bullae. CONCLUSION:
      We report a 46-year-old woman with a figurate erythema presentation of bullous
      pemphigoid.

PMID- 22417999
TI  - Lupus erythematosus-associated primary and secondary anetoderma.
AB  - BACKGROUND: Anetoderma (focal loss of dermal elastic tissue) can either be
      primary, which is an idiopathic occurrence of anetoderma in normal areas of the
      skin, or secondary, which is preceded by an inflammatory dermatosis in the same
      location. OBJECTIVE: Sporadic reports of lupus erythematosus-associated
      anetoderma have been described in the literature. All reported cases were
      positive for antiphospholipid antibodies. We present a patient with primary and
      secondary anetoderma with chronic lupus dermatitis and negative antiphospholipid
      antibodies. METHOD AND RESULTS: A middle-aged woman presented with a soft nodule
      with a wrinkled surface on her left arm and an erythematous atrophic plaque with
      a nodular surface on the chest. Skin biopsy from the left arm showed epidermal
      atrophy without inflammatory changes. Histologic findings of the lesion on the
      chest were consistent with chronic lupus dermatitis and secondary anetoderma.
      Laboratory investigations showed positive antinuclear antibody anti-double
      stranded deoxyribonucleic acid (DNA) antibody but negative antiphospholipid
      antibodies. CONCLUSION: Primary and secondary anetodermas may occur in patients
      of lupus dermatitis without positive antiphospholipid antibodies.

PMID- 22418000
TI  - T-cell lymphoma/Sezary syndrome in a liver transplant recipient.
AB  - BACKGROUND: Cutaneous T-cell lymphoma is a rare subtype of posttransplantation
      lymphoproliferative disease, with only 29 cases reported in the literature to
      date, the majority of which are post-renal transplantation. Only a few were
      reported after pancreas, heart, and bone marrow transplantation. There have been
      no reports of cutaneous T-cell lymphoma following liver transplantation to date.
      OBJECTIVE: We report a case of a 76-year-old male who developed generalized
      eczematous eruption 13 years after a liver transplantation. Investigations showed
      that it was Epstein-Barr virus-negative, CD3-positive, and CD4-positive cutaneous
      T-cell lymphoma with Sezary cells in the blood. CONCLUSION: This shows that
      cutaneous T-cell lymphoma/Sezary syndrome can also develop after liver
      transplantation. To our knowledge, there are no similar reports in the English
      literature.

PMID- 22418001
TI  - Histaminergic ligands injected into the nucleus basalis magnocellularis
      differentially affect fear conditioning consolidation.
AB  - The role of the nucleus basalis magnocellularis (NBM) in fear conditioning
      encoding is well established. In the present report, we investigate the
      involvement of the NBM histaminergic system in consolidating fear memories. The
      NBM was injected bilaterally with ligands of histaminergic receptors immediately
      after contextual fear conditioning. Histaminergic compounds, either alone or in
      combination, were stereotaxically administered to different groups of adult male
      Wistar rats and memory was assessed as conditioned freezing duration 72 h after
      administration. This protocol prevents interference with NBM function during
      either acquisition or retrieval phases, hence restricting the effect of
      pharmacological manipulations to fear memory consolidation. The results presented
      here demonstrate that post-training H3 receptors (H3R) blockade with the
      antagonist/inverse agonist thioperamide or activation with immepip in the NBM
      potentiates or decreases, respectively, freezing response at retrieval.
      Thioperamide induced memory enhancement seems to depend on H2R, but not H1R
      activation, as the H2R antagonist zolantidine blocked the effect of thioperamide,
      whereas the H1R antagonist pyrilamine was ineffective. Furthermore, the H2R
      agonist ampthamine improved fear memory expression independently of the H3R
      agonist effect. Our results indicate that activation of post-synaptic H2R within
      the NBM by endogenous histamine is responsible for the potentiated expression of
      fear responses. The results are discussed in terms of activation of H3 auto- and
      heteroreceptors within the NBM and the differential effect of H3R ligands on fear
      memory consolidation in distinct brain regions.

PMID- 22418002
TI  - Malignant hypertension with reversible brainstem hypertensive encephalopathy and
      thrombotic microangiopathy.
AB  - A 42-year-old woman presented with headache and nausea. Severe hypertension,
      renal dysfunction, thrombocytopenia, and anemia were present. A magnetic
      resonance imaging (MRI) scan of her head revealed widespread hyperintense lesions
      located in the brainstem and cerebellum on T2-weighted and fluid-attenuated
      inversion recovery imaging. Hypertensive encephalopathy was suspected, and
      antihypertensive therapy was started. A second MRI of the patient's head on day
      12 of hospitalization revealed that the hyperintensities in the brainstem and
      cerebellum had almost disappeared, and that thrombocytopenia, anemia, and renal
      dysfunction had also gradually improved. Test results led to a diagnosis of
      malignant hypertension. This patient was regarded as suffering from malignant
      hypertension with reversible brainstem hypertensive encephalopathy (RBHE) and
      thrombotic microangiopathy (TMA). RBHE and TMA are known to occur as
      complications of malignant hypertension, but there has been no previous report of
      them occurring simultaneously. RBHE and TMA related to malignant hypertension are
      both conditions that can be improved by the rapid institution of antihypertensive
      therapy, and as such, early diagnosis and treatment are important. When treating
      patients with malignant hypertension, the possibility that it may be complicated
      by both RBHE and TMA must be kept in mind.

PMID- 22418003
TI  - So much to do, so little time.

PMID- 22418004
TI  - Five-year outcome after laparoscopic anterior partial versus Nissen
      fundoplication: four randomized trials.
AB  - OBJECTIVE: To compare longer term (5-year) outcomes for reflux control and
      postsurgery side effects after laparoscopic anterior (90 degrees  and 180 degrees
      ) partial versus Nissen fundoplication for gastroesophageal reflux. BACKGROUND:
      Laparoscopic Nissen fundoplication is the most frequently performed surgical
      procedure for gastroesophageal reflux. It achieves excellent control of reflux,
      but in some patients it is followed by troublesome side effects. To reduce the
      risk of side effects laparoscopic anterior partial fundoplication variants have
      been advocated, although some studies suggest poorer reflux control. METHODS:
      From 1995 to 2003, 461 patients with gastroesophageal reflux were enrolled in 4
      randomized controlled trials comparing anterior partial versus Nissen
      fundoplication. Two trials evaluated anterior 180 degrees  and 2 anterior 90
      degrees  partial fundoplication. The original trial data were combined, and a
      reanalysis from original data was undertaken to determine outcomes at 5 years
      follow-up. Reflux symptom control and side effects were evaluated in a blinded
      fashion using standardized questionnaires, including 0 to 10 analog scores (0 =
      no symptoms, 10 = severe symptoms). RESULTS: At 5 years, patients who underwent
      an anterior 90 degrees  or 180 degrees  partial fundoplication had less side
      effects than those who underwent Nissen fundoplication and were equally satisfied
      with the overall outcome. Reflux control, measured by heartburn scores and
      antisecretory medication use, was similar for anterior 180 degrees  partial
      versus Nissen fundoplication, but inferior after anterior 90 degrees  partial
      versus Nissen fundoplication. CONCLUSIONS: Anterior 180 degrees  partial
      fundoplication achieves durable control of reflux symptoms and fewer side effects
      compared with Nissen fundoplication. Reflux control after anterior 90 degrees 
      partial fundoplication appears less effective than after Nissen fundoplication.
      This data supports the use of anterior 180 degrees  partial fundoplication for
      the surgical treatment of gastroesophageal reflux.

PMID- 22418005
TI  - Prospective randomized double-blind study of temporary sacral nerve stimulation
      in patients with rectal evacuatory dysfunction and rectal hyposensitivity.
AB  - OBJECTIVE: Prospective randomized double-blind placebo-controlled crossover trial
      of 14 female patients (median age 52 [30-69] years) with proctographically
      defined evacuatory dysfunction (ED) and demonstrable rectal hyposensitivity
      (elevated thresholds to balloon distension in comparison with age- and sex
      matched controls). BACKGROUND: Sacral nerve stimulation (SNS) is an evolving
      treatment for constipation. However, variable outcomes might be improved by
      better patient selection. Evidence that the effect of SNS may be mediated by
      modulation of afferent signaling promotes a role in patients with ED associated
      with rectal hyposensation. METHODS: SNS was performed by the standard 2-stage
      technique (temporary then permanent implantation). During a 4-week period of
      temporary stimulation, patients were randomized ON-OFF/OFF-ON for two 2-week
      periods. Before insertion (PRE), and during each crossover period, primary
      (rectal sensory thresholds) and secondary (bowel diaries, constipation, and GIQoL
      [gastrointestinal quality of life] scores) outcome variables were blindly
      assessed. RESULTS: Thirteen patients completed the trial. Following stimulation,
      defecatory desire volumes to rectal balloon distension were normalized in 10 of
      13 patients (PRE: mean 277 mL [234-320] vs ON: 163 mL [133-193] vs OFF: 220 mL
      [183-257 mL]; P = 0.006) and maximum tolerable volume in 9 of 13 (PRE: mean 350
      mL [323-377] vs ON: 262 mL [219-305] vs OFF: 298 mL [256-340 mL]; P = 0.012).
      There was a significant increase in the percentage of successful bowel movements
      (PRE: median 43% [0-100] vs ON: 89% [11-100] vs OFF: 83% [11-100]; P = 0.007) and
      Wexner constipation scores improved (PRE: median 19 [9-26] vs ON: 10 [6-27] vs
      OFF: 13 [5-29]; P = 0.01). There were no significant changes in disease-specific
      or generic quality of life measures. Eleven patients progressed to permanent
      stimulation (9/11 success at 19 months). CONCLUSIONS: Most patients with chronic
      constipation secondary to ED with rectal hyposensitivity responded to temporary
      SNS. The physiological results presented support a mechanistic role for rectal
      afferent modulation.

PMID- 22418006
TI  - Surgical techniques for parastomal hernia repair: a systematic review of the
      literature.
AB  - BACKGROUND: Parastomal hernias are a frequent complication of enterostomies that
      require surgical treatment in approximately half of patients. This systematic
      review aimed to evaluate and compare the safety and effectiveness of the surgical
      techniques available for parastomal hernia repair. METHODS: Systematic review was
      performed in accordance with PRISMA. Assessment of methodological quality and
      selection of studies of parastomal hernia repair was done with a modified MINORS.
      Subgroups were formed for each surgical technique. Primary outcome was recurrence
      after at least 1-year follow-up. Secondary outcomes were mortality and
      postoperative morbidity. Outcomes were analyzed using weighted pooled proportions
      and logistic regression. RESULTS: Thirty studies were included with the majority
      retrospective. Suture repair resulted in a significantly increased recurrence
      rate when compared with mesh repair (odds ratio [OR] 8.9, 95% confidence interval
      [CI] 5.2-15.1; P < 0.0001). Recurrence rates for mesh repair ranged from 6.9% to
      17% and did not differ significantly. In the laparoscopic repair group, the
      Sugarbaker technique had less recurrences than the keyhole technique (OR 2.3, 95%
      CI 1.2-4.6; P = 0.016). Morbidity did not differ between techniques. The overall
      rate of mesh infections was low (3%, 95% CI 2) and comparable for each type of
      mesh repair. CONCLUSIONS: Suture repair of parastomal hernia should be abandoned
      because of increased recurrence rates. The use of mesh in parastomal hernia
      repair significantly reduces recurrence rates and is safe with a low overall rate
      of mesh infection. In laparoscopic repair, the Sugarbaker technique is superior
      over the keyhole technique showing fewer recurrences.

PMID- 22418007
TI  - The Surgical Mortality Probability Model: derivation and validation of a simple
      risk prediction rule for noncardiac surgery.
AB  - OBJECTIVE: To develop a 30-day mortality risk index for noncardiac surgery that
      can be used to communicate risk information to patients and guide clinical
      management at the "point-of-care," and that can be used by surgeons and hospitals
      to internally audit their quality of care. BACKGROUND: Clinicians rely on the
      Revised Cardiac Risk Index to quantify the risk of cardiac complications in
      patients undergoing noncardiac surgery. Because mortality from noncardiac causes
      accounts for many perioperative deaths, there is also a need for a simple bedside
      risk index to predict 30-day all-cause mortality after noncardiac surgery.
      METHODS: Retrospective cohort study of 298,772 patients undergoing noncardiac
      surgery during 2005 to 2007 using the American College of Surgeons National
      Surgical Quality Improvement Program database. RESULTS: The 9-point S-MPM
      (Surgical Mortality Probability Model) 30-day mortality risk index was derived
      empirically and includes three risk factors: ASA (American Society of
      Anesthesiologists) physical status, emergency status, and surgery risk class.
      Patients with ASA physical status I, II, III, IV or V were assigned either 0, 2,
      4, 5, or 6 points, respectively; intermediate- or high-risk procedures were
      assigned 1 or 2 points, respectively; and emergency procedures were assigned 1
      point. Patients with risk scores less than 5 had a predicted risk of mortality
      less than 0.50%, whereas patients with a risk score of 5 to 6 had a risk of
      mortality between 1.5% and 4.0%. Patients with a risk score greater than 6 had
      risk of mortality more than 10%. S-MPM exhibited excellent discrimination (C
      statistic, 0.897) and acceptable calibration (Hosmer-Lemeshow statistic 13.0, P =
      0.023) in the validation data set. CONCLUSIONS: Thirty-day mortality after
      noncardiac surgery can be accurately predicted using a simple and accurate risk
      score based on information readily available at the bedside. This risk index may
      play a useful role in facilitating shared decision making, developing and
      implementing risk-reduction strategies, and guiding quality improvement efforts.

PMID- 22418008
TI  - Upregulation of proapoptotic microRNA mir-125a after massive small bowel
      resection in rats.
AB  - OBJECTIVE: Short bowel syndrome remains a condition of high morbidity and
      mortality, and current therapeutic options carry significant side effects. To
      identify new treatments we focused on postresection changes in microRNAs--short
      noncoding RNAs, which suppress target genes--and suggest a previously
      undiscovered role for microRNA-125a (mir-125a) in intestinal adaptation. METHODS:
      Rats underwent either 80% massive small bowel resection or transection and were
      harvested after 48 hours. Jejunum was harvested for microRNA microarrays, laser
      capture microdissection, and RNA and protein analysis. Mir-125a was overexpressed
      in intestinal epithelium-6 (crypt-derived) cells (IEC-6) and effects on
      proliferation and apoptosis determined using MTS and flow cytometry. Expression
      of potential targets of mir-125a in rat jejunum and IEC-6 cells was determined
      using quantitative real-time polymerase chain reaction (RNA) and Western blotting
      (protein). RESULTS: Resection upregulated mir-125a and mir-214 by 2.4-folds and
      3.2-folds, respectively. Highest levels of expression were noted in the crypt
      fraction. Mir-125a overexpression induced apoptosis and resultant growth arrest
      in IEC-6 cells. The expression of the prosurvival Bcl-2 family member Mcl-1 was
      downregulated in both mir-125a-overexpressing IEC-6 cells and in jejunum of
      resected rats, confirming Mcl-1 as a previously undiscovered target of mir-125a.
      CONCLUSIONS: Upregulation of mir-125a suppresses the prosurvival protein Mcl1,
      producing the increase in apoptosis known to accompany the proliferative changes
      characteristic of intestinal adaptation. Our data highlight a potential role for
      microRNAs as mediators of the adaptive process and may facilitate the development
      of new therapeutic options for short bowel syndrome.

PMID- 22418009
TI  - Functional and medical outcomes after tailored surgery for pain due to chronic
      pancreatitis.
AB  - OBJECTIVE: We measured a comprehensive set of outcome measures after different
      surgical procedures for painful chronic pancreatitis (CP) at long-term follow-up.
      BACKGROUND: Pain caused by CP can be alleviated through operative intervention
      with type of procedure depending on anatomical abnormalities. Outcome measures
      include functional (pain relief, quality of life [QoL]), medical (endo- and
      exocrine function), and clinical (reoperation) results reported by patient.
      METHODS: A cross-sectional cohort of 223 consecutive patients who underwent
      surgical drainage, head resection, or left-sided pancreas resection, depending on
      anatomical abnormalities, was analyzed. Participating patients were reassessed
      during a prospectively scheduled outpatient clinic visit. RESULTS: At follow-up,
      44 patients had died; 146 of 179 living patients consented to participate in the
      study. After 63 months (range: 14-268), 68% reported no or little pain, 19%
      reported intermediate pain, and 12% reported severe pain. Preoperative daily
      opioid use (OR: 3.04; 95% confidence interval [CI]: 1.09-8.49) and high numbers
      of preceding endoscopic procedures (OR [odds ratio]: 3.89; 95% CI: 1.01-14.9)
      were associated with persistent severe pain. Compared with the general
      population, physical more than mental QoL remained impaired (P < 0.05). At follow
      up, endocrine insufficiency was present in 57% of patients and exocrine
      insufficiency was present in 77%. Independently, a head resection and a
      reoperation for any cause were moderately associated with new-onset diabetes (P <
      0.1). Compared with patients who underwent left-sided resection, the risk of
      developing exocrine insufficiency after surgery was higher after drainage or head
      resection. After 20 months (interquartile range: 10-51) after surgery, 26 (12%)
      of 223 patients underwent 1 or more elective reoperations. CONCLUSIONS: Operative
      intervention for painful CP, tailored to anatomical abnormalities, results in
      excellent to fair long-term pain relief, but approximately 10% of patients do not
      respond. QoL scores remained slightly compromised. High preoperative pain levels,
      suggested through daily opioid use and high numbers of endoscopic procedures, are
      associated with less favorable outcome.

PMID- 22418010
TI  - Optimization of staging of the neck with prophylactic central and lateral neck
      dissection for papillary thyroid carcinoma.
AB  - OBJECTIVE: To analyze the yield and rate of node metastases (pN1) for
      prophylactic central (CND) and lateral neck dissection (LND) for papillary
      thyroid carcinoma, the risk factors for pN1, and outcomes. BACKGROUND:
      Prophylactic CND and LND are not routinely employed. Adjuvant radioiodine
      treatment may be modulated, however, by surgical staging of the neck. METHODS:
      Retrospective study, consecutive patients ultrasonographically classified cN0
      treated with prophylactic CND, and lateral LND (levels III and IV). The number of
      nodes was resected and the incidence of pN1 was recorded. RESULTS: For 317
      patients (254 women, mean age 44 years, mean tumor size 17 mm), the number of
      lymph nodes was 5 for unilateral CND, 9 for bilateral CND, and 12 for LND. pN1
      stage was 42% overall: 23% for unilateral CND, 39% for bilateral CND, and 23% for
      LND (median number of metastatic nodes = 2 for each). Fifty-five percent of the
      patients staged pN1 had metastatic nodes in the lateral neck. Ten percent had
      more than 10 metastatic nodes and/or more than 3 nodes with extra capsular
      spread. pN1 was correlated with tumor size (P = 0.0025), extrathyroidal tumor
      extension (P < 0.0001), male sex (P = 0.0006), and age younger than 45 years (P =
      0.0003). Permanent hypoparathyroidism and unintentional recurrent nerve paralysis
      occurred in 2 cases each. Patients staged pN0 received less radioiodine than
      patients staged pN1 (median 30 vs 100 mCi, P < 0.0001). CONCLUSIONS: For staging,
      bilateral prophylactic CND is preferable to unilateral CND. Prophylactic CND with
      LND optimizes staging providing a basis for a personalized approach for adjuvant
      radioiodine.

PMID- 22418011
TI  - Risk factors for complications in groin hernia surgery: a national register
      study.
AB  - OBJECTIVE: This study aims to analyze and identify risk factors for postoperative
      complications and analyze the relative risk of reoperation for recurrence for
      respective complication. BACKGROUND: The outcome of groin hernia surgery is
      evaluated mostly by comparing recurrence rates and long-term pain. The aim of
      this observational population-based registry study was to identify risk factors
      for postoperative complications and analyze the relative risk of reoperation for
      recurrence for respective complication. METHODS: Using data from the nationwide
      Swedish Hernia Register between 1998 and 2009, 150,514 herniorrhaphies were
      analyzed with respect to postoperative complications occurring within 30 days of
      surgery. RESULTS: Risk factors significantly affecting the rate of postoperative
      complications were laparoscopic repair (odds ratio [OR] 1.35, 95% confidence
      interval [CI] 1.24-1.47) and open preperitoneal techniques (OR: 1.31, 95% CI:
      1.15-1.49), with open anterior mesh as reference category. Other significant risk
      factors were general (OR: 1.30, 95% CI: 1.23-1.37) and regional anesthesia (OR:
      1.53, 95% CI: 1.43-1.63), with local anesthesia as reference category, emergency
      procedures (OR: 1.53, 95% CI: 1.43-1.63); recurrent hernia repair (OR: 1.39, 95%
      CI: 1.27-1.52); femoral hernia (OR: 1.30, 95% CI: 1.14-1.48); aged older than 65
      years (OR: 1.26, 95% CI: 1.21-1.31); and duration of surgery exceeding 50 minutes
      (OR: 1.27, 95% CI: 1.22-1.33). CONCLUSIONS: Open anterior approach and surgery
      under local anesthesia are associated with less risk of postoperative
      complications.

PMID- 22418013
TI  - Alterations of the brain reward system in antipsychotic naive schizophrenia
      patients.
AB  - BACKGROUND: Various schizophrenic symptoms are suggested to be linked to a
      dysfunction of the brain reward system. Several studies have found alterations in
      the reward processing in patients with schizophrenia; however, most previous
      findings might be confounded by medication effects. METHODS: Thirty-one
      antipsychotic-naive schizophrenia patients and 31 age- and gender-matched healthy
      control subjects were examined with functional magnetic resonance imaging while
      playing a variant of the monetary incentive delay task. The task variant made it
      possible to separate overall salience (defined as arousing events) into
      behavioral salience (events where a predicted reward requires performance) and
      valence anticipation (the anticipation of a monetarily significant outcome).
      Furthermore, the evaluation of monetary gain and loss was assessed. RESULTS:
      During reward anticipation, patients had a significant attenuation of the
      activation in ventral tegmentum, ventral striatum, and anterior cingulate cortex
      during presentation of salient cues. This signal attenuation in ventral striatum
      was correlated with the degree of positive symptoms. Signal attenuation was most
      pronounced for behavioral salience and nonsignificant for value anticipation.
      Furthermore, patients showed a changed activation pattern during outcome
      evaluation in right prefrontal cortex. CONCLUSION: Our results suggest that
      changes during reward anticipation in schizophrenia are present from the
      beginning of the disease. This supports a possible involvement of reward
      disturbances in the pathophysiology of schizophrenia. The most pronounced changes
      were seen in relation to overall salience. In ventral striatum these changes were
      associated with the degree of positive symptoms.

PMID- 22418014
TI  - Development of cortical surface area and gyrification in attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: Delineation of the cortical anomalies underpinning attention
      deficit/hyperactivity disorder (ADHD) can powerfully inform pathophysiological
      models. We previously found that ADHD is characterized by a delayed maturation of
      prefrontal cortical thickness. We now ask if this extends to the maturation of
      cortical surface area and gyrification. METHODS: Two hundred thirty-four children
      with ADHD and 231 typically developing children participated in the study, with
      837 neuroanatomic magnetic resonance images acquired longitudinally. We defined
      the developmental trajectories of cortical surfaces and gyrification and the
      sequence of cortical maturation, as indexed by the age at which each cortical
      vertex attained its peak surface area. RESULTS: In both groups, the maturation of
      cortical surface area progressed in centripetal waves, both lateral (starting at
      the central sulcus and frontopolar regions, sweeping toward the mid and superior
      frontal gyrus) and medial (descending down the medial prefrontal cortex, toward
      the cingulate gyrus). However, the surface area developmental trajectory was
      delayed in ADHD. For the right prefrontal cortex, the median age by which 50% of
      cortical vertices attained peak area was 14.6 years (SE = .03) in ADHD,
      significantly later than in typically developing group at 12.7 years (SE = .03)
      [log-rank test chi(1)2 = 1300, p < .00001]. Similar, but less pronounced, delay
      was found in the left hemispheric lobes. There were no such diagnostic
      differences in the developmental trajectories of cortical gyrification.
      CONCLUSIONS: The congruent delay in cortical thickness and surface area direct
      attention away from processes that selectively affect one cortical component
      toward mechanisms controlling the maturation of multiple cortical dimensions.

PMID- 22418012
TI  - Oxytocin gene polymorphisms influence human dopaminergic function in a sex
      dependent manner.
AB  - BACKGROUND: Oxytocin, classically involved in social and reproductive activities,
      is increasingly recognized as an antinociceptive and anxiolytic agent, effects
      which may be mediated via oxytocin's interactions with the dopamine system. Thus,
      genetic variation within the oxytocin gene (OXT) is likely to explain variability
      in dopamine-related stress responses. As such, we examined how OXT variation is
      associated with stress-induced dopaminergic neurotransmission in a healthy human
      sample. METHODS: Fifty-five young healthy volunteers were scanned using
      [11C]raclopride positron emission tomography while they underwent a standardized
      physical and emotional stressor that consisted of moderate levels of experimental
      sustained deep muscle pain, and a baseline, control state. Four haplotype tagging
      single nucleotide polymorphisms located in regions near OXT were genotyped.
      Measures of pain, affect, anxiety, well-being and interpersonal attachment were
      also assessed. RESULTS: Female rs4813625 C allele carriers demonstrated greater
      stress-induced dopamine release, measured as reductions in receptor availability
      from baseline to the pain-stress condition relative to female GG homozygotes. No
      significant differences were detected among males. We also observed that female
      rs4813625 C allele carriers exhibited higher attachment anxiety, higher trait
      anxiety and lower emotional well-being scores. In addition, greater stress
      induced dopamine release was associated with lower emotional well-being scores in
      female rs4813625 C allele carriers. CONCLUSIONS: Our results suggest that
      variability within the oxytocin gene appear to explain interindividual
      differences in dopaminergic responses to stress, which are shown to be associated
      with anxiety traits, including those linked to attachment style, as well as
      emotional well-being in women.

PMID- 22418015
TI  - Interaction of the serotonin transporter-linked polymorphic region and
      environmental adversity: increased amygdala-hypothalamus connectivity as a
      potential mechanism linking neural and endocrine hyperreactivity.
AB  - BACKGROUND: Gene by environment (G*E) interaction between genetic variation in
      the promoter region of the serotonin transporter gene (serotonin transporter
      linked polymorphic region [5-HTTLPR]) and stressful life events (SLEs) has been
      extensively studied in the context of depression. Recent findings suggest
      increased neural and endocrine stress sensitivity as a possible mechanism
      conveying elevated vulnerability to psychopathology. Furthermore, these G*E
      mediated alterations very likely reflect interrelated biological processes.
      METHODS: In the present functional magnetic resonance imaging study, amygdala
      reactivity to fearful stimuli was assessed in healthy male adults (n = 44), who
      were previously found to differ with regard to endocrine stress reactivity as a
      function of 5-HTTLPR * SLEs. Furthermore, functional connectivity between the
      amygdala and the hypothalamus was measured as a potential mechanism linking
      elevated neural and endocrine responses during stressful/threatening situations.
      The study sample was carefully preselected regarding 5-HTTLPR genotype and SLEs.
      RESULTS: We report significant G*E interaction on neural response patterns and
      functional amygdala-hypothalamus connectivity. Specifically, homozygous carriers
      of the 5-HTTLPR S' allele with a history of SLEs (S'S'/high SLEs group) displayed
      elevated bilateral amygdala activation in response to fearful faces. Within the
      same sample, a comparable G*E interaction effect has previously been demonstrated
      regarding increased cortisol reactivity, indicating a cross-validation of
      heightened biological stress sensitivity. Furthermore, S'S'/high SLEs subjects
      were characterized by an increased functional coupling between the right amygdala
      and the hypothalamus, thus indicating a potential link between neural and
      endocrine hyperreactivity. CONCLUSIONS: The present findings contribute to the
      ongoing debate on 5-HTTLPR * SLEs interaction and are discussed with respect to
      clinical implications.

PMID- 22418016
TI  - Understanding rural and remote health: a framework for analysis in Australia.
AB  - People living in rural and remote areas face challenges in accessing appropriate
      health services, many of which struggle to recruit and retain staff. While
      researchers have documented these issues in Australia and internationally, rural
      health remains reactive to current problems and lacks comprehensive
      understanding. This paper presents a conceptual framework that can be used to
      better understand specific rural and remote health situations. The framework
      consists of six key concepts: geographic isolation, the rural locale, local
      health responses, broader health systems, social structures and power. Viewed
      through Giddens' theory of structuration, the framework suggests that rural
      health is understood as spatial and social relations among local residents as
      well as the actions of local health professionals/consumers that are both enabled
      and constrained by broader health systems and social structures. The framework
      provides a range of stakeholders with a guide to understanding rural and remote
      health.

PMID- 22418017
TI  - Evidence-based guidelines for interpreting change scores for the European
      Organisation for the Research and Treatment of Cancer Quality of Life
      Questionnaire Core 30.
AB  - AIM: To use published literature and experts' opinion to investigate the clinical
      meaning and magnitude of changes in the Quality of Life (QOL) of groups of
      patients measured with the European Organisation for the Research and Treatment
      of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). METHODS: An
      innovative method combining systematic review of published studies, expert
      opinions and meta-analysis was used to estimate large, medium, and small mean
      changes over time for QLQ-C30 scores. RESULTS: Nine hundred and eleven papers
      were identified, leading to 118 relevant papers. One thousand two hundred and
      thirty two mean changes in QOL over time were combined in the meta-analysis, with
      timescales ranging from four days to five years. Guidelines were produced for
      trivial, small, and medium size classes, for each subscale and for improving and
      declining scores separately. Estimates for improvements were smaller than
      respective estimates for declines. CONCLUSIONS: These guidelines can be used to
      aid sample size calculations and interpretation of mean changes over time from
      groups of patients. Observed mean changes in the QLQ-C30 scores are generally
      small in most clinical situations, possibly due to response shift. Careful
      consideration is needed when planning studies where QOL changes over time are of
      primary interest; the timing of follow up, sample attrition, direction of QOL
      changes, and subscales of primary interest are key considerations.

PMID- 22418018
TI  - Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis:
      diagnosis, genetics, pathophysiology and treatment.
AB  - Macrophage activation syndrome (MAS) is a severe, frequently fatal complication
      of systemic juvenile idiopathic arthritis (sJIA) with features of
      hemophagocytosis leading to coagulopathy, pancytopenia, and liver and central
      nervous system dysfunction. MAS is overt in 10% of children with sJIA but occurs
      subclinically in another 30-40%. It is difficult to distinguish sJIA disease
      flare from MAS. Development of criteria for establishing MAS as part of sJIA are
      under way and will hopefully prove sensitive and specific. Mutations in cytolytic
      pathway genes are increasingly being recognized in children who develop MAS as
      part of sJIA. Identification of these mutations may someday assist in MAS
      diagnosis. Defects in cytolytic genes have provided murine models of MAS to study
      pathophysiology and treatment. Recently, the first mouse model of MAS not
      requiring infection but rather dependent on repeated stimulation through Toll
      like receptors was reported. This provides a model of MAS that may more
      accurately reflect MAS pathology in the setting of autoinflammation or
      autoimmunity. This model confirms the importance of a balance between pro- and
      anti-inflammatory cytokines. There has been remarkable progress in the use of
      anti-pro-inflammatory cytokine therapy, particularly against interleukin-1, in
      the treatment of secondary forms of MAS, such as in sJIA.

PMID- 22418019
TI  - Anti-inflammatory effects of DX-890, a human neutrophil elastase inhibitor.
AB  - BACKGROUND: Neutrophil elastase (NE)-mediated inflammation contributes to lung
      damage in cystic fibrosis (CF). We investigated if DX-890, a small-protein NE
      inhibitor, could reduce neutrophil trans-epithelial migration and reduce activity
      released from neutrophils and NE-induced cytokine expression in airway epithelial
      cells. METHODS: Activated blood neutrophils (CF and healthy) treated +/-DX-890
      were assayed for NE activity. Transmigration of calcein-labeled neutrophils was
      studied using a 16HBE14o(-) epithelial monolayer. IL-8 release from primary nasal
      epithelial monolayers (CF and healthy) was measured after treatment +/-DX-890 and
      NE or CF sputum. RESULTS: DX-890 reduced NE activity from neutrophils (CF and
      healthy) and reduced neutrophil transmigration. DX-890 pre-treatment reduced IL-8
      release from epithelial cells of healthy or CF subjects after stimulation with NE
      and CF sputum sol. All improvements with DX-890 were statistically significant
      (p<0.05). CONCLUSIONS: DX-890 reduces NE-mediated transmigration and
      inflammation. NE inhibition could be useful in managing neutrophilic airway
      inflammation in CF.

PMID- 22418020
TI  - Depth-dependent magnetism in epitaxial MnSb thin films: effects of surface
      passivation and cleaning.
AB  - Depth-dependent  magnetism in MnSb(0001) epitaxial films has been studied by
      combining experimental methods with different surface specificities: polarized
      neutron reflectivity, x-ray magnetic circular dichroism (XMCD), x-ray resonant
      magnetic scattering and spin-polarized low energy electron microscopy (SPLEEM). A
      native oxide ~4.5 nm thick covers air-exposed samples which increases the film's
      coercivity. HCl etching efficiently removes this oxide and in situ surface
      treatment of etched samples enables surface magnetic contrast to be observed in
      SPLEEM. A thin Sb capping layer prevents oxidation and preserves ferromagnetism
      throughout the MnSb film. The interpretation of Mn  L(3,2) edge XMCD data is
      discussed.

PMID- 22418021
TI  - [18F]FDG labeling of neural stem cells for in vivo cell tracking with positron
      emission tomography: inhibition of tracer release by phloretin.
AB  - The introduction of neural stem cells into the brain has promising therapeutic
      potential for the treatment of neurodegenerative diseases. To monitor the
      cellular replacement therapy, that is, to determine stem cell migration,
      survival, and differentiation, in vivo tracking methods are needed. Ideally,
      these tracking methods are noninvasive. Noninvasive tracking methods that have
      been successfully used for the visualization of blood-derived progenitor cells
      include magnetic resonance imaging and radionuclide imaging using single-photon
      emission computed tomography (SPECT) and positron emission tomography (PET). The
      SPECT tracer In-111-oxine is suitable for stem cell labeling, but for studies in
      small animals, the higher sensitivity and facile quantification that can be
      obtained with PET are preferred. Here the potential of 2'-[18F]fluoro-2'-deoxy-D
      glucose ([18F]-FDG), a PET tracer, for tracking of neural stem cell (NSCs)
      trafficking toward an inflammation site was investigated. [18F]-FDG turns out to
      be a poor radiopharmaceutical to label NSCs owing to the low labeling efficiency
      and substantial release of radioactivity from these cells. Efflux of [18F]-FDG
      from NSCs can be effectively reduced by phloretin in vitro, but inhibition of
      tracer release is insufficient in vivo for accurate monitoring of stem cell
      trafficking.

PMID- 22418022
TI  - Accepting the torch.

PMID- 22418023
TI  - Codon-optimized Luciola italica luciferase variants for mammalian gene expression
      in culture and in vivo.
AB  - Luciferases have proven to be useful tools in advancing our understanding of
      biologic processes. Having a multitude of bioluminescent reporters with different
      properties is highly desirable. We characterized codon-optimized thermostable
      green- and red-emitting luciferase variants from the Italian firefly Luciola
      italica for mammalian gene expression in culture and in vivo. Using lentivirus
      vectors to deliver and stably express these luciferases in mammalian cells, we
      showed that both variants displayed similar levels of activity and protein half
      lives as well as similar light emission kinetics and higher stability compared to
      the North American firefly luciferase. Further, we characterized the red-shifted
      variant for in vivo bioluminescence imaging. Intramuscular injection of tumor
      cells stably expressing this variant into nude mice yielded a robust luciferase
      activity. Light emission peaked at 10 minutes post-d-luciferin injection and
      retained > 60% of signal at 1 hour. Similarly, luciferase activity from
      intracranially injected glioma cells expressing the red-shifted variant was
      readily detected and used as a marker to monitor tumor growth over time. Overall,
      our characterization of these codon-optimized luciferases lays the groundwork for
      their further use as bioluminescent reporters in mammalian cells.

PMID- 22418024
TI  - In vivo evidence that the increase in matrix metalloproteinase activity occurs
      early after cerebral ischemia.
AB  - There is controversy over whether matrix metalloproteinases (MMPs) are activated
      during the early therapeutic window following ischemic stroke. Ex vivo, an
      increase was reported as early as 4 hours, whereas in vivo, no increase was found
      until 24 hours postischemia. We used fluorescence diffuse optical tomography to
      image MMP activity following experimental cerebral ischemia; increased MMP
      activity was observed in the ischemic area as early as 3 to 6 hours after
      ischemic onset and correlated with the volume of ischemic cerebral tissue.
      Therefore, MMP activation is an immediate early response to cerebral ischemia
      concurrent with the therapeutic window.

PMID- 22418025
TI  - Multimodality imaging of somatostatin receptor-positive tumors with nuclear and
      bioluminescence imaging.
AB  - Multimodal bioluminescence (BLI) and single-photon emission computed
      tomography/computed tomography (SPECT/CT) imaging were investigated as means to
      monitor somatostatin receptor subtype 2 (SST2)-positive neuroendocrine tumors as
      both a subcutaneously implanted and a liver metastasis animal model in mice and
      rats. Ultimately, such a model will be of use for studying SST2-targeted peptide
      receptor radionuclide therapy (PRRT). CA20948 cells were transfected with a green
      fluorescent protein/luciferase plasmid construct. Cells were inoculated
      subcutaneously in the shoulder of nude mice: nontransfected cells in the left
      shoulder and transfected cells in the right shoulder. BLI, SPECT/CT imaging,
      biodistribution analysis, and ex vivo autoradiography of the tumors were
      performed. BLI and SPECT/CT imaging were also performed on an intrahepatic tumor
      model in the rat. Caliper volume measurement of transfected tumors could be
      correlated with BLI measurements (R2 = .76). SPECT/CT imaging showed high levels
      of accumulation of 111In-DTPA-octreotide in control and transfected tumors, which
      was confirmed by biodistribution analysis and autoradiography. Subcapsular
      inoculation of transfected cells in rat liver resulted in an intrahepatic tumor,
      which could be visualized by both SPECT/CT and BLI. Transfection of CA20948 tumor
      cells did not alter the growth properties of the cell line or the expression of
      SST2. Transfected tumors could be clearly visualized by BLI and SPECT/CT imaging.
      The transfected SST2-positive tumor cell line could represent a novel preclinical
      model for tumor monitoring in studies that aim at further optimizing PRRT for
      neuroendocrine tumors.

PMID- 22418026
TI  - Rapid visualization of human tumor xenografts through optical imaging with a near
      infrared fluorescent anti-epidermal growth factor receptor nanobody.
AB  - Given that overexpression of the epidermal growth factor receptor (EGFR) is found
      in many types of human epithelial cancers, noninvasive molecular imaging of this
      receptor is of great interest. A number of studies have employed monoclonal
      antibodies as probes; however, their characteristic long half-life in the
      bloodstream has encouraged the development of smaller probes. In this study, an
      anti-EGFR nanobody-based probe was developed and tested in comparison with
      cetuximab for application in optical molecular imaging. To this aim, the anti
      EGFR nanobody 7D12 and cetuximab were conjugated to the near-infrared fluorophore
      IRDye800CW. 7D12-IR allowed the visualization of tumors as early as 30 minutes
      postinjection, whereas with cetuximab-IR, no signal above background was observed
      at the tumor site. Quantification of the IR-conjugated proteins in the tumors
      revealed ~ 17% of injected dose per gram 2 hours after injection of 7D12-IR,
      which was significantly higher than the tumor uptake obtained 24 hours after
      injection of cetuximab-IR. This difference is associated with the superior
      penetration and distribution of 7D12-IR within the tumor. These results
      demonstrate that this anti-EGFR nanobody conjugated to the NIR fluorophore has
      excellent properties for rapid preclinical optical imaging, which holds promise
      for its future use as a complementary diagnostic tool in humans.

PMID- 22418028
TI  - Endothelial adhesion of targeted microbubbles in both small and great vessels
      using ultrasound radiation force.
AB  - The effectiveness of microbubble-mediated ultrasound molecular imaging and drug
      delivery has been significantly affected by the axial laminar flow of vessels
      which prevents ultrasound contrast agents (UCAs) from targeting vascular
      endothelium. Studies show that acoustic manipulation could increase targeted UCA
      adhesion in microcirculation and some small vessels. In this study we demonstrate
      that ultrasound radiation force (USRF) can also significantly enhance the
      targeted adhesion of microbubbles in both small and great vessels. Our results
      indicate that the UCA adhesion targeted to ICAM-1 expressed on mouse cremaster
      microvascular endothelial cells increase about 9-fold when USRF is applied at 1
      MHz and 73.9 kPa. The adhesion of anti-CD34 microbubbles to the endothelia of rat
      abdominal aorta was visually analyzed using scanning electron microscopy for the
      first time and thousands of microbubbles were found attached to the aortic
      endothelia after USRF application at the same acoustic parameters. Our data
      illustrate that targeted adhesion of anti-CD34 microbubbles is possible in normal
      abdominal aorta and we demonstrate the potential of using USRF in molecular
      imaging of a vascular target.

PMID- 22418027
TI  - Imaging in vivo extracellular pH with a single paramagnetic chemical exchange
      saturation transfer magnetic resonance imaging contrast agent.
AB  - The measurement of extracellular pH (pHe) has potential utility for cancer
      diagnoses and for assessing the therapeutic effects of pH-dependent therapies. A
      single magnetic resonance imaging (MRI) contrast agent that is detected through
      paramagnetic chemical exchange saturation transfer (PARACEST) was designed to
      measure tumor pH(e) throughout the range of physiologic pH and with magnetic
      resonance saturation powers that are not harmful to a mouse model of cancer. The
      chemical characterization and modeling of the contrast agent Yb(3+)-1,4,7,10
      tetraazacyclododecane-1,4,7-triacetic acid,10-o-aminoanilide (Yb-DO3A-oAA)
      suggested that the aryl amine of the agent forms an intramolecular hydrogen bond
      with a proximal carboxylate ligand, which was essential for generating a
      practical chemical exchange saturation transfer (CEST) effect from an amine. A
      ratio of CEST effects from the aryl amine and amide was linearly correlated with
      pH throughout the physiologic pH range. The pH calibration was used to produce a
      parametric pH map of a subcutaneous flank tumor on a mouse model of MCF-7 mammary
      carcinoma. Although refinements in the in vivo CEST MRI methodology may improve
      the accuracy of pHe measurements, this study demonstrated that the PARACEST
      contrast agent can be used to generate parametric pH maps of in vivo tumors with
      saturation power levels that are not harmful to a mouse model of cancer.

PMID- 22418030
TI  - In vivo evaluation of 1-O-(4-(2-fluoroethyl-carbamoyloxymethyl)-2-nitrophenyl)-O
      beta-D-glucopyronuronate: a positron emission tomographic tracer for imaging beta
      glucuronidase activity in a tumor/inflammation rodent model.
AB  - beta-Glucuronidase (beta-GUS) plays an important role in inflammation and
      degenerative processes. The enzyme has also been investigated as a target in
      prodrug therapy for cancer. To investigate the role of beta-GUS in pathologies
      and to optimize beta-GUS-based prodrug therapies, we recently developed a
      positron emission tomographic (PET) tracer, 1-O-(4-(2-fluoroethyl
      carbamoyloxymethyl)-2-nitrophenyl)-O-beta-D-glucopyronuronate ([18F]FEAnGA),
      which proved to be selectively cleaved by beta-GUS. Here we present the in vivo
      evaluation of [18F]FEAnGA for imaging of beta-GUS in a tumor/inflammation model.
      Ex vivo biodistribution of [18F]FEAnGA was conducted in healthy rats. PET imaging
      and pharmacokinetic modeling were performed in Wistar rats bearing C6 tumors of
      different sizes and sterile inflammation. The biodistribution studies of
      [18F]FEAnGA indicated low uptake in major organs and rapid excretion through the
      renal pathway. MicroPET studies revealed three times higher uptake in the viable
      part of larger C6 gliomas than in smaller C6 gliomas. Uptake in inflamed muscle
      was significantly higher than in control muscle. The distribution volume of
      [18F]FEAnGA in the viable part of the tumor correlated well with the cleavage of
      the tracer to [18F]fluoroethylamine and the spacer 4-hydroxy-3-nitrobenzyl
      alcohol. [18F]FEAnGA is a PET tracer able to detect increased activity of beta
      GUS in large solid tumors and in inflamed tissues.

PMID- 22418029
TI  - Monitoring the induction of heat shock factor 1/heat shock protein 70 expression
      following 17-allylamino-demethoxygeldanamycin treatment by positron emission
      tomography and optical reporter gene imaging.
AB  - The cell response to proteotoxic cell stresses is mediated primarily through
      activation of heat shock factor 1 (HSF1). This transcription factor plays a major
      role in the regulation of the heat shock proteins (HSPs), including HSP70. We
      demonstrate that an [124I]iodide-pQHNIG70 positron emission tomography (PET)
      reporter system that includes an inducible HSP70 promoter can be used to image
      and monitor the activation of the HSF1/HSP70 transcription factor in response to
      drug treatment (17-allylamino-demethoxygeldanamycin [17-AAG]). We developed a
      dual imaging reporter (pQHNIG70) for noninvasive imaging of the heat shock
      response in cell culture and living animals previously and now study HSF1/HSP70
      reporter activation in both cell culture and tumor-bearing animals following
      exposure to 17-AAG. 17-AAG (10-1,000 nM) induced reporter expression; a 23-fold
      increase was observed by 60 hours. Good correspondence between reporter
      expression and HSP70 protein levels were observed. MicroPET imaging based on
      [124I]iodide accumulation in pQHNIG70-transduced RG2 xenografts showed a
      significant 6.2-fold reporter response to 17-AAG, with a corresponding increase
      in tumor HSP70 and in tumor human sodium iodide symporter and green fluorescent
      protein reporter proteins. The HSF1 reporter system can be used to screen
      anticancer drugs for induction of cytotoxic stress and HSF1 activation both in
      vitro and in vivo.

PMID- 22418033
TI  - Danshensu ameliorates the cognitive decline in streptozotocin-induced diabetic
      mice by attenuating advanced glycation end product-mediated neuroinflammation.
AB  - Spatial learning and memory are impaired in diabetic animals. The interaction of
      advanced glycation end products (AGEs) with the receptor of AGEs (RAGE),
      resulting in the activation of nuclear factor-kappaB (NF-kappaB), plays an
      important role in pathways leading to the cytotoxic effects to neurons.
      Danshensu, a compound from Salvia miltiorrhiza Bunge, has neuroprotective
      effects. This study aimed to investigate the role of AGE-mediated
      neuroinflammation in learning and memory deficits and the effect of Danshensu on
      the cognitive decline in diabetic mice. C57BL/6 mice were injected
      intraperitoneally with streptozotocin. Sodium Danshensu (sodium salt of
      Danshensu) was administered at a dose of 15, 30, or 60 mg/kg for 12 weeks. The
      results showed that diabetes caused impairment in acquisition and retrieval
      processes, as demonstrated by performance in the Morris water maze test.
      Danshensu not only reduced the mean escape latency but also increased the
      percentage of time spent in the target quadrant. Western blot analysis revealed
      that there was a significant increase in the expression of RAGE, p-p38, and COX
      2, and the NF-kappaB activation. Danshensu partly blocked the expression of RAGE,
      p-p38, and COX-2, and NF-kappaB activation, and inhibited the increase of TNF
      alpha, IL-6, and PGE2. However, Danshensu did not affect body weight and the
      levels of blood glucose, glycosylated hemoglobin, insulin, and AGEs. These
      findings demonstrate that AGE-mediated neuroinflammation plays an important role
      in learning and memory deficits in diabetic mice and that Danshensu may provide a
      potential alternative for the prevention of cognitive impairment associated with
      diabetes by attenuating AGE-mediated neuroinflammation.

PMID- 22418034
TI  - Approximating distributions in stochastic learning.
AB  - On-line machine learning algorithms, many biological spike-timing-dependent
      plasticity (STDP) learning rules, and stochastic neural dynamics evolve by Markov
      processes. A complete description of such systems gives the probability densities
      for the variables. The evolution and equilibrium state of these densities are
      given by a Chapman-Kolmogorov equation in discrete time, or a master equation in
      continuous time. These formulations are analytically intractable for most cases
      of interest, and to make progress a nonlinear Fokker-Planck equation (FPE) is
      often used in their place. The FPE is limited, and some argue that its
      application to describe jump processes (such as in these problems) is
      fundamentally flawed. We develop a well-grounded perturbation expansion that
      provides approximations for both the density and its moments. The approach is
      based on the system size expansion in statistical physics (which does not give
      approximations for the density), but our simple development makes the methods
      accessible and invites application to diverse problems. We apply the method to
      calculate the equilibrium distributions for two biologically-observed STDP
      learning rules and for a simple nonlinear machine-learning problem. In all three
      examples, we show that our perturbation series provides good agreement with Monte
      Carlo simulations in regimes where the FPE breaks down.

PMID- 22418032
TI  - Bystander-mediated stimulation of proteolipid protein-specific regulatory T
      (Treg) cells confers protection against experimental autoimmune encephalomyelitis
      (EAE) via TGF-beta.
AB  - To assess the potency of regulatory T (Treg) cells induced against an irrelevant
      Ag, mice were orally vaccinated with Salmonella expressing Escherichia coli
      colonization factor antigen I fimbriae. Isolated CD25+ and CD25-CD4+ T cells were
      adoptively transferred to naive mice, and Treg cells effectively protected
      against experimental autoimmune encephalomyelitis (EAE), unlike Treg cells from
      Salmonella vector-immunized mice. This protection was abrogated upon in vivo
      neutralization of TGF-beta, resulting in elevated IL-17 and loss of IL-4 and IL
      10 production. Thus, Treg cells induced to irrelevant Ags offer a novel approach
      to treat autoimmune diseases independent of auto-Ag.

PMID- 22418035
TI  - An iterative epsilon-optimal control scheme for a class of discrete-time
      nonlinear systems with unfixed initial state.
AB  - In this paper, a finite horizon iterative adaptive dynamic programming (ADP)
      algorithm is proposed to solve the optimal control problem for a class of
      discrete-time nonlinear systems with unfixed initial state. A new epsilon-optimal
      control algorithm based on the iterative ADP approach is proposed that makes the
      performance index function iteratively converge to the greatest lower bound of
      all performance indices within an error epsilon in finite time. The convergence
      analysis of the proposed ADP algorithm in terms of performance index function and
      control policy is conducted. The optimal number of control steps can also be
      obtained by the proposed epsilon-optimal control algorithm for the unfixed
      initial state. Neural networks are used to approximate the performance index
      function, and compute the optimal control policy, respectively, for facilitating
      the implementation of the epsilon-optimal control algorithm. Finally, a
      simulation example is given to show the effectiveness of the proposed method.

PMID- 22418036
TI  - Human small intestinal and colonic tissue mounted in the Ussing chamber as a tool
      for characterizing the intestinal absorption of drugs.
AB  - The purpose of this study was to validate human small intestinal and colonic
      tissue mounted in the Ussing chamber as a tool for predicting the oral drug
      absorption in humans with the main focus on moderately and poorly permeable
      compounds. The obtained apparent permeability coefficient (P(app)) of eleven test
      compounds was compared to their fraction absorbed (Fa) in humans taken from the
      literature. Beside the conventional P(app) a new parameter, the apparent
      permeability coefficient total (P(app,total)), involving both the apical-to
      basolateral permeability and the time-dependent compound accumulation in the
      tissue was established. The permeability of lucifer yellow (LY), a fluorescent
      marker of the paracellular pathway and the test compounds showed no obvious
      differences between small intestine and colon. Furthermore, small intestinal and
      colonic tissue from a single donor showed similar permeability of both LY and a
      transcellularly transported compound metoprolol. All test compounds including low
      molecular weight hydrophilic compounds such as metformin, atenolol, sulpiride and
      famotidine showed adequate permeability reflecting human Fa values (R(2)=0.87).
      The P(app) values of digoxin, a P-glycoprotein (P-gp) substrate, were not
      significantly affected by the addition of verapamil, a P-gp inhibitor. In
      contrast, the P(app,total) values of digoxin increased approximately threefold in
      the presence of verapamil. In conclusion, both small intestinal and colonic
      tissue mounted in the Ussing chamber provide a good opportunity to predict the
      oral drug absorption rate in humans even for moderately and poorly absorbed
      compounds. The novel calculation of P(app,total) allows the study of the carrier
      mediated drug-drug interactions in human intestine.

PMID- 22418037
TI  - Fast-track surgery and technical nuances to reduce complications after radical
      cystectomy and intestinal urinary diversion with the modified Indiana pouch.
AB  - OBJECTIVES: With the purpose to reduce the complications of radical cystectomy
      and intestinal urinary reconstruction a perioperative protocol based on fast
      track surgery principles and technical modifications of the original surgical
      technique was applied to patient candidates for etherotopic bladder substitution.
      Our protocol included pre-, intra-, and postoperative interventions. The
      technical variations of the modified Indiana pouch technique were focused on
      intestinal anastomosis to restore bowel continuity, uretero-colonic anastomoses,
      and capacity of the reservoir. RESULTS AND LIMITATIONS: From 2003 to 2010, 68
      consecutive patients participated in the study. Two patients died due to surgical
      complications (2.9%). Overall, 24 of 68 patients experienced complications
      (35.3%). Surgery was needed under general anaesthesia for seven patients (10.2%)
      and under local anaesthesia for four (5.9%). Medical complications were
      encountered in 13 of 68 patients (19.1%). According to Clavien grading,
      complications were grade 5 in two patients, grade 4 in two patients, grade 3b in
      five patients, grade 3a in four patients, grade 2 in nine patients, and grade 1b
      in two patients. A limitation of our series is that patients were recruited at a
      single urologic centre and were operated by a single surgeon. Findings need
      validation. CONCLUSIONS: Progress in the perioperative management of major
      surgery and technical refinements can contribute to reduced complications. In
      addition, the use of objective reporting tools will facilitate comparison of
      studies.

PMID- 22418038
TI  - Management and prognosis of endometrioid borderline tumors of the ovary.
AB  - BACKGROUND: The Endometrioid Borderline ovarian tumor (EBOT) is the third most
      common histological subtype of borderline ovarian tumors. Very little is known
      about the prognosis and management of this entity. This paper consists of a
      review of the literature and an analysis of clinical series. STUDY DESIGN: A
      review of the literature on this topic was conducted identifying series reporting
      consecutive cases of EBOT using 2 search engines (MEDLINE and Pubmed). Personal
      data on this topic have been included and concern a series of patients treated
      between 1985 and 2009 for EBOT. These cases included in this series had complete
      data concerning patient management and follow-up > 12 months. RESULTS: 16
      patients were studied: 7 had been treated conservatively and 9 radically. All
      16/16 patients had stage I disease at the initial diagnosis but one patient had
      also developed synchronous endometrioid adenocarcinoma of the uterine corpus.
      After a median time of 24 months (range, 12-132) post treatment, one (1/16)
      patient had developed two recurrences. She remains disease-free 42 months after
      the end of treatment of the last recurrence. These data were compared to the
      results of 4 series previously reported in the literature. In fact, the present
      series reports on the first recurrence in EBOT (which was an invasive lesion).
      CONCLUSION: Endometrioid borderline ovarian tumors carry a good prognosis. Most
      EBOT tumors are stage I, therefore surgical staging is not necessary in most of
      the cases. However, uterine curettage is required in cases of uterine
      preservation.

PMID- 22418040
TI  - A case of unexplained hypoxemia.
AB  - We present a patient with acute-onset dyspnea and unexplained severe hypoxemia.
      No signs of severe cardiopulmonary disease, pulmonary arterial hypertension, or
      pulmonary embolism were present. The patient was diagnosed with hepatopulmonary
      syndrome, since liver disease of alcoholic  origin was present, markedly
      increased alveolar-arterial oxygen difference existed, and intrapulmonary
      vascular dilations were demonstrated. The condition of the patient did not
      improve and he was referred for liver transplantation, which is the only
      treatment option with documented efficacy.  The case highlights the importance of
      thinking outside the thorax when evaluating patients with dyspnea.

PMID- 22418041
TI  - Effect of body mass index on early morbidity and mortality after isolated
      coronary artery bypass graft surgery.
AB  - OBJECTIVES: Obesity is a risk factor for morbidity after isolated coronary artery
      bypass grafting. This study aimed to analyze the sole effect of body mass index
      (BMI) on early morbidity and mortality in patients after isolated coronary artery
      bypass grafting. DESIGN: This study was retrospective and used an electronic
      database of anesthesia information management. SETTING: A single community
      hospital. PARTICIPANTS: The data of 803 consecutive patients after isolated on
      pump coronary artery bypass grafting were analyzed retrospectively; off-pump
      cases were excluded. INTERVENTION: According to measured BMI, patients were
      divided into 5 groups: underweight (BMI <20 kg/m(2)), normal weight (BMI 20.0
      24.9 kg/m(2)), overweight (BMI 25.0-29.9 kg/m(2)), obese (BMI 30.0-34.9 kg/m(2)),
      and morbidly obese (BMI >34.9 kg/m(2)). Early postoperative morbidity and
      mortality were evaluated using logistic regression analysis. MEASUREMENTS AND
      MAIN RESULTS: Early cumulative postoperative mortality was 3.9% (32 of 803
      patients). Mortality was recorded in 3 underweight (n = 15, 20%, odds ratio [OR]
      6.54, p = 0.001), 9 normal-weight (n = 159, 5.7%, OR 1.62, p = 0.228), 12
      overweight (n = 371, 3.2%, OR 0.68, p = 0.314), 6 obese (n = 199, 3.0%, OR 0.69,
      p = 0.421), and 2 morbidly obese (n = 59, 3.4%, OR 0.83, p = 0.808) patients.
      Prolonged intensive care unit stay (p < 0.001), prolonged hospital stay (p <
      0.001), and mortality (p = 0.01) were significantly more common in patients in
      the underweight group than in the other groups. Univariate and multivariate
      logistic regression analyses showed that underweight, hypertension, and chronic
      renal failure were independent risk factors for mortality. CONCLUSIONS:
      Underweight patients with a BMI <20 kg/m(2) are at increased risk of
      postoperative complications and mortality compared with normal-weight or
      overweight subjects.

PMID- 22418042
TI  - Emergent echocardiography in noncardiac surgical patients.

PMID- 22418039
TI  - American Cancer Society, American Society for Colposcopy and Cervical Pathology,
      and American Society for Clinical Pathology screening guidelines for the
      prevention and early detection of cervical cancer.
AB  - An update to the American Cancer Society (ACS) guideline regarding screening for
      the early detection of cervical precancerous lesions and cancer is presented. The
      guidelines are based on a systematic evidence review, contributions from six
      working groups, and a recent symposium co-sponsored by the ACS, American Society
      for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical
      Pathology (ASCP), which was attended by 25 organizations. The new screening
      recommendations address age-appropriate screening strategies, including the use
      of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g.,
      management of screen positives and screening interval for screen negatives) of
      women after screening, age at which to exit screening, future considerations
      regarding HPV testing alone as a primary screening approach, and screening
      strategies for women vaccinated against HPV16/18 infections.

PMID- 22418043
TI  - beta-blocker withdrawal among patients presenting for surgery from home.
AB  - OBJECTIVE: This study sought to measure the prevalence of perioperative beta
      blocker noncompliance by patients who were prescribed long-term beta-blocker
      therapy and presented for surgery from home. The effect of patient noncompliance
      on the presenting heart rate on the day of surgery also was examined. DESIGN:
      Prospective observational study with outcome data obtained from reviews of
      medical records. SETTING: The preoperative clinic and operating rooms of a
      Veterans Administration hospital. PARTICIPANTS: Patients on long-term beta
      blocker therapy who presented from home for surgery. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Demographic and comorbidity data and data on self
      reported compliance to beta-blocker therapy, vital signs on the initial day of
      surgery, and recent ambulatory vital signs were collected. Ten of 50 subjects
      (20%; 95% confidence interval, 9-31) reported not taking their beta-blocker on
      the day of surgery. These self-reported nonadherers exhibited a higher presenting
      heart rate on the day of surgery than adherent subjects (median, 78 v 65
      beats/min; p = 0.02 by Wilcoxon rank-sum test). The difference-in-difference
      analysis in heart rate between baseline primary care and the day of surgery also
      was statistically significant between compliant and noncompliant subjects (-7 v +
      12.5 beats/min; p < 0.00001). CONCLUSIONS: Patient self-report and physiologic
      data documented a failure to take beta-blockers and possible beta-blocker
      withdrawal in 20% of patients who presented for surgery from home. If these
      findings are confirmed in larger studies, improved patient understanding of and
      compliance with medication instructions during preoperative visits should be a
      focus of future quality improvement initiatives.

PMID- 22418044
TI  - Effects of levosimendan on renal function in patients undergoing coronary artery
      surgery.
AB  - OBJECTIVES: To evaluate the effect of levosimendan on postoperative renal
      function in patients with compromised heart function undergoing on-pump coronary
      artery bypass graft surgery. DESIGN: A prospective, randomized, placebo
      controlled, double-blind substudy. SETTING: Cardiothoracic surgery,
      anesthesiology, and intensive care units at 2 university hospitals. PARTICIPANTS:
      Sixty patients with left ventricular ejection fraction <=50% were randomized into
      2 parallel treatment groups. INTERVENTIONS: Levosimendan or placebo was started
      after the induction of anesthesia with a 12-MUg/kg bolus in 10 minutes followed
      by the infusion of 0.2 MUg/kg/min for the next 23 hours and 50 minutes.
      MEASUREMENTS AND RESULTS: Serum cystatin C and plasma creatinine were measured at
      baseline; at 6 and 24 hours after declamping the aorta; and on the 1st, 2nd, and
      5th postoperative days. Urine N-acetyl-beta-glucosaminidase (U-NAG) was measured
      at baseline and at 6 and 24 hours after declamping of the aorta. Renal function
      was estimated with calculated glomerular filtration rate (eGFR). The changes in
      plasma creatinine, serum cystatin C, and urine NAG were not significant among the
      placebo and the levosimendan groups at any of the measuring points. CONCLUSIONS:
      After coronary artery surgery, levosimendan did not have a significant influence
      on the kidney function measured with these specific kidney markers.

PMID- 22418045
TI  - A small circular structure in the right atrium: a cause for right atrial and
      ventricular dilatation?

PMID- 22418046
TI  - Intraoperative epicardial sonography as a useful adjunct to repair of coronary
      artery dissection.

PMID- 22418047
TI  - A case of symptomatic left ventricular diverticulum.

PMID- 22418048
TI  - A common symptom in two uncommon coexistent conditions: glomus jugulare tumor and
      dysphagia lusoria.

PMID- 22418049
TI  - Cerebral venous thrombosis presenting as subarachnoid hemorrhage: report of two
      cases.

PMID- 22418050
TI  - Beyond herniation.

PMID- 22418051
TI  - Regulation of the HPA axis is related to song complexity and measures of
      phenotypic quality in song sparrows.
AB  - Regulation of the hypothalamic-pituitary-adrenal (HPA) axis is a key component of
      the vertebrate stress response. Prior studies have found that variation in HPA
      responses were correlated to measures of fitness and physiological condition. In
      addition, sexually-selected traits have also been found to correlate to measures
      of condition. The proximate mechanisms responsible for such covariation between
      sexually selected traits and measures of quality are unclear, but could involve
      variation in HPA regulation. We investigated whether HPA activity is related to
      song complexity, body size/condition and leukocyte profiles in wild male song
      sparrows (Melospiza melodia). We characterized three aspects of HPA activity: 1)
      response to restraint stress; 2) negative feedback, assessed by the ability of
      exogenous dexamethasone to suppress corticosterone levels; and 3) adrenal
      sensitivity to exogenous adrenocorticotropic hormone (ACTH). Birds with lower
      responses to restraint stress had more complex song and more heterophils and
      higher heterophil to lymphocyte (H:L) ratios. Birds with more effective negative
      feedback were larger and had fewer heterophils and lower H:L ratios, suggesting
      lower levels of physiological stress or infection. We observed no relationship
      between adrenal sensitivity to exogenous ACTH and any of the factors. These
      findings illustrate important relationships between HPA activity, song
      complexity, and morphological and physiological traits. Song complexity may thus
      provide receivers with information about the ability of the singer to cope with
      stressors.

PMID- 22418052
TI  - Effect of downscaling nano-copper interconnects on the microstructure revealed by
      high resolution TEM-orientation-mapping.
AB  - In this work, a recently developed electron diffraction technique called
      diffraction scanning transmission electron microscopy (D-STEM) is coupled with
      precession electron microscopy to obtain quantitative local texture information
      in damascene copper interconnects (1.8 um-70 nm in width) with a spatial
      resolution of less than 5 nm. Misorientation and trace analysis is performed to
      investigate the grain boundary distribution in these lines. The results reveal
      strong variations in texture and grain boundary distribution of the copper lines
      upon downscaling. Lines of width 1.8 um exhibit a strong <111> normal texture and
      comprise large micron-size grains. Upon downscaling to 180 nm, a {111}<110> bi
      axial texture has been observed. In contrast, narrower lines of widths 120 and 70
      nm reveal sidewall growth of {111} grains and a dominant <110> normal texture.
      The microstructure in these lines comprises clusters of small grains separated by
      high angle boundaries in the vicinity of large grains. The fraction of coherent
      twin boundaries also reduces with decreasing line width.

PMID- 22418054
TI  - Dysfunction of default-mode network in encephalopathy with a reversible corpus
      callosum lesion.
AB  - Increasing attention has been paid recently to the study of spontaneous brain
      activity; moreover, particular attention has been paid to the concept of a
      default-mode network of brain function. Although the functional significance of
      the default-mode network remains a matter of debate, it has been suggested to be
      a candidate for the network subserving basic functions related to consciousness.
      We report the case of a 29-year-old man with encephalopathy and a reversible
      lesion of the entire corpus callosum. Despite resolution of corpus callosum
      lesion on magnetic resonance imaging (MRI) within 1 week, the patient
      persistently presented disturbance of consciousness. Resting-state functional MRI
      revealed that the posterior cingulate cortex/precuneus was functionally
      disconnected from other brain regions within the default-mode network. Our case
      report suggests that assessment of the functional connectivity in the resting
      state default-mode network could be a useful marker of consciousness disturbance
      even in the presence of a reversible brain lesion.

PMID- 22418055
TI  - Operative and nonoperative linguistic outcomes in brain injury patients.
AB  - OBJECTIVE AND BACKGROUND: Linguistic function is one of vulnerable aspects of
      traumatic brain injury (TBI) which may have destructive effects on patients'
      communicative activities and daily life, years following trauma. This paper
      attempts to answer the controversy whether surgery affects increase and decrease
      of linguistic impairment or not. MATERIALS AND METHODS: Two hundred forty-one TBI
      patients aged 18-65 with abnormal CT findings and at least 20 minute post-trauma
      amnesia (PTA), who were conscious at discharge, participated in this study. Based
      on operative intervention, the samples were divided into two groups: operative
      and nonoperative. Cognitive and aphasic deficits were inspected formally and
      pragmatic disorder was informally appraised at discharge. RESULTS: The groups had
      no significant differences in aphasia incidence and language pragmatic
      impairment, though they were significantly distinctive in aphasia subcategories
      and cognitive deficit after trauma. Fluent aphasia was more common in both groups
      alike. In aphasia subcategories, however, transcortical sensory aphasia (TSA) in
      operative and anomia in nonoperative group were the most prevalent. Several
      variables appeared strikingly related to higher aphasia in operative groups as
      follows: moderate to severe injury, 18-35 and over 50 years of age, more than 1
      week PTA, intracranial surgery of multiple lesions in left or bilateral
      hemisphere fronto-temporal cortex plus post-trauma cognitive and pragmatic
      impairments, and diffuse axonal injuries. DISCUSSION: Almost certainly,
      meaningful drop of cognitive function post surgery roots back in significant loss
      of initial consciousness level. Related factors to postoperative aphasia suggest
      taking policies through surgery intervention. Discerning the indispensable
      contributions of neurosurgeons, neurolinguists, and neuroscientists, results
      inspire more clinical future studies.

PMID- 22418056
TI  - Anisotropic magnetic properties and superzone gap formation in CeGe single
      crystal.
AB  - Single crystals of CeGe and its non-magnetic analog LaGe have been grown by the
      Czochralski method. The CeGe compound crystallizes in the orthorhombic FeB-type
      crystal structure with the space group Pnma (#62). The anisotropic magnetic
      properties have been investigated for well oriented single crystals by measuring
      the magnetic susceptibility, electrical resistivity and heat capacity. It has
      been found that CeGe orders antiferromagnetically at 10.5 K. Both transport and
      magnetic studies have revealed large anisotropy, reflecting the orthorhombic
      crystal structure. The magnetization data at 1.8 K reveal metamagnetic
      transitions along the [010] direction at 4.8 and 6.4 T and along the [100]
      direction at a critical field of 10.7 T, while the magnetization along the [001]
      direction increases linearly without any anomaly up to a field of 16 T. From the
      magnetic susceptibility and the magnetization measurements it has been found that
      the [010] direction is the easy axis of magnetization. The electrical resistivity
      along the three crystallographic directions exhibits an upturn at T(N),
      indicating superzone gap formation below T(N) in this compound. We have performed
      crystal electric field analysis on the magnetic susceptibility and the heat
      capacity data and found that the ground state is a doublet, and the energies of
      splitting from the ground state to the first and second excited doublet states
      were estimated to be 39 and 111 K, respectively.

PMID- 22418057
TI  - Contribution of the rostral ventromedial medulla to post-anxiety induced
      hyperalgesia.
AB  - Rats exposed to an elevated plus maze (EPM) with four open arms display
      antinociception while on the maze and hyperalgesia immediately upon removal.
      Little is known about the neural mechanisms underlying EPM-induced
      antinociception and the subsequent hyperalgesia except that the antinociception
      is not mediated by endogenous opioids. The objective of the present study was to
      test the hypothesis that endogenous cannabinoids and/or the rostral ventromedial
      medulla (RVM) contributes to EPM-induced antinociception. Administration of the
      CB1 receptor antagonist AM251 (1mg/kg, i.p.) had no effect on baseline
      nociception to formalin administration into the hindpaw or on the antinociception
      produced by placing a rat on the open EPM. Likewise, inactivation of the RVM by
      microinjecting the GABA(A) receptor agonist muscimol (10 ng/0.5 MUL) had no
      effect on the antinociceptive effect of placing a rat in the EPM. However, RVM
      inactivation blocked the hyperalgesia produced upon removal from the EPM.
      Although distinct classes of RVM neurons inhibit and facilitate nociception, the
      present data demonstrate that the antinociception induced by the EPM and the
      subsequent hyperalgesia is mediated by distinct neural pathways.

PMID- 22418058
TI  - The effect of ageing on neurogenesis and oxidative stress in the
      APP(swe)/PS1(deltaE9) mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder
      characterised by memory loss and impaired cognitive function. One of the
      hallmarks of AD is the formation of beta amyloid (Abeta) plaques. Abeta has
      neurodegenerative properties and aggregates in the brain, causing inflammation,
      oxidative stress and eventually neuronal loss. In AD, adult neurogenesis in the
      dentate gyrus (DG) of the hippocampus is known to be impaired. We tested how
      ageing affects neurogenesis and oxidative stress in the commonly used
      APP(SWE)/PS1(DeltaE9) mouse model of AD and their wild type (wt) littermate
      controls aged 3, 5, 10 and 15months. Progenitor cell proliferation in the DG of
      APP/PS1 was lower at 3, 5 and 10months compared to controls, while oxidative
      stress in APP/PS1 mice was increased in the cortex at 3 and 5months of age
      compared to controls. The numbers of new neurons in the DG were decreased in
      APP/PS1 mice at 10 and 15months. In APP/PS1 mice, Abeta plaques were evident in
      the cortex from 3months onward; however these were small and few. Plaque size and
      number consistently increased with age in APP/PS1 mice. These results show that
      the damage to the brain occurs already very early in the brain, and although
      neurogenesis is impaired, it is still active even in late stage AD. Therefore,
      therapies would have the best effects if started early, but promoting
      neurogenesis may act in a protective and reconstructive way even in later stages
      of AD.

PMID- 22418059
TI  - Knockout of the gamma-aminobutyric acid receptor subunit alpha4 reduces
      functional delta-containing extrasynaptic receptors in hippocampal pyramidal
      cells at the onset of puberty.
AB  - Increased plasmalemmal localization of alpha4betadelta GABA(A) receptors (GABARs)
      occurs in the hippocampal pyramidal cells of female mice at pubertal onset (Shen
      et al., 2010). This increase occurs on both dendritic spines and shafts of CA1
      pyramidal cells and is in response to hormone fluctuations that occur at pubertal
      onset. However, little is known about how the alpha4 and delta subunits
      individually mediate the formation of functional, plasmalemmal alpha4betadelta
      GABARs. To determine whether expression of the alpha4 subunit is necessary for
      plasmalemmal delta subunit localization at pubertal onset, electron microscopic
      immunocytochemistry (EM-ICC) was employed. CA1 pyramidal cells of female alpha4
      knockout (KO) mice were tested for plasmalemmal levels of the delta subunit
      within dendritic spine and shaft profiles at the onset of puberty. EM-ICC
      revealed that the alpha4 and delta subunits localize on dendritic spines and
      shafts at sites extrasynaptic to GABAergic input at pubertal onset in tissue of
      wild-type (WT) mice. At pubertal onset, plasmalemmal localization of the delta
      subunit is reduced 45.9% on dendritic spines, and 56.7% on dendritic shafts with
      KO of the alpha4 subunit, as compared to WT tissue, yet levels of intracellular
      delta immunoreactivity remain unchanged. The decline in plasmalemmal localization
      is manifested as decreased responsiveness to the GABA agonist gaboxadol at
      concentrations that are selective for delta-containing GABARs. Additionally,
      alpha4 KO mice have larger dendritic spine and shaft profiles. Our findings
      demonstrate that alpha4 subunit expression strongly influences the pubertal
      increase of delta subunits at the plasma membrane, and that genetic deletion of
      alpha4 serves as a functional knock-down of delta-containing GABARs.

PMID- 22418060
TI  - Motor function and dopamine release measurements in transgenic Huntington's
      disease model rats.
AB  - Huntington's disease (HD) is a fatal, genetic, neurodegenerative disorder
      characterized by deficits in motor and cognitive function. Here, we have
      quantitatively characterized motor deficiencies and dopamine release dynamics in
      transgenic HD model rats. Behavioral analyses were conducted using a newly
      developed force-sensing runway and a previously-developed force-plate actometer.
      Gait disturbances were readily observed in transgenic HD rats at 12 to 15months
      of age. Additionally, dopamine system challenge by ip injection of amphetamine
      also revealed that these rats were resistant to the expression of focused
      stereotypy compared to wild-type controls. Moreover, dopamine release, evoked by
      the application of single and multiple electrical stimulus pulses applied at
      different frequencies, and measured using fast-scan cyclic voltammetry at carbon
      fiber microelectrodes, was diminished in transgenic HD rats compared to age
      matched wild-type control rats. Collectively, these results underscore the
      potential contribution of dopamine release alterations to the expression of motor
      impairments in transgenic HD rats.

PMID- 22418061
TI  - Axonal transport of adeno-associated viral vectors is serotype-dependent.
AB  - We have previously shown that adeno-associated virus type 2 (AAV2) undergoes
      anterograde axonal transport in rat and non-human primate brain. We screened
      other AAV serotypes for axonal transport and found that AAV6 is transported
      almost exclusively in a retrograde direction and, in the same way as AAV2, it is
      also neuron-specific in rat brain. Our findings show that axonal transport of AAV
      is serotype dependent and this has implications for gene therapy of neurological
      diseases such as Huntington's disease.

PMID- 22418062
TI  - Modulating vascular intimal hyperplasia using HSV-1 mutant requires activated
      MEK.
AB  - Outcomes of cardiovascular procedures, such as angioplasty and stent or bypass
      grafting are limited by failure, predominantly caused by pathological smooth
      muscle cell (SMC) proliferation, known as intimal hyperplasia. Local delivery of
      a genetically engineered herpes simplex virus (HSV) is known to block vascular
      SMC proliferation while allowing for re-endothelialization. However, the
      mechanism this mutant virus uses to prevent SMC hyperplasia is unknown. The Ras
      signaling cascade is activated in SMCs undergoing hyperplasia leading to
      phosphorylation of the mitogen-activated protein kinase (MAPK). In this study we
      tested the hypothesis that MAPK kinase (MEK) activity is the molecular basis by
      which SMCs are susceptible to mutant HSV. We show that genetically engineered
      herpes simplex-1 viruses (HSV-1) can target proliferating SMCs. We demonstrate
      that the molecular basis of this HSV-1 anti-proliferative effect is MEK
      activation in SMCs. We demonstrate efficacy and practicality of the MEK-dependent
      HSV-1 for the treatment of intimal hyperplasia in a clinically relevant in vivo
      model. Important to this strategy is the ability to modulate the effects by
      controlling viral dose. These results propel genetically engineered HSV-1 therapy
      towards clinical evaluation in treatment of intimal hyperplasia.

PMID- 22418064
TI  - Percutaneous methods of vector delivery in preclinical models.
AB  - Cardiovascular disease remains a leading cause of hospitalization and mortality
      worldwide. Conventional heart failure treatment is making steady and substantial
      progress to reduce the burden of disease. Nevertheless novel therapies and
      especially cardiac gene therapy have been emerging in the past and successfully
      made their way into first clinical trials. Gene therapy was initially a visionary
      treatment strategy for inherited, monogenetic diseases but has now developed to
      have potential for polygenic diseases as atherosclerosis, arrhythmias and heart
      failure. These novel therapeutic strategies require testing in clinically
      relevant animal models to transition from 'bench to bedside'. One of the major
      hurdles for effective cardiovascular gene therapy is the delivery of the viral
      vectors to the heart. In this review we present the currently available vector
      mediated cardiac gene delivery methods in vivo considering the specific merits
      and deficiencies.

PMID- 22418063
TI  - Gene delivery technologies for cardiac applications.
AB  - Ischemic heart disease (IHD) and heart failure (HF) are major causes of morbidity
      and mortality in the Western society. Advances in understanding the molecular
      pathology of these diseases, the evolution of vector technology, as well as
      defining the targets for therapeutic interventions has placed these conditions
      within the reach of gene-based therapy. One of the cornerstones of limiting the
      effectiveness of gene therapy is the establishment of clinically relevant methods
      of genetic transfer. Recently there have been advances in direct and
      transvascular gene delivery methods with the use of new technologies. Current
      research efforts in IHD are focused primarily on the stimulation of angiogenesis,
      modify the coronary vascular environment and improve endothelial function with
      localized gene-eluting catheters and stents. In contrast to standard IHD
      treatments, gene therapy in HF primarily targets inhibition of apoptosis,
      reduction in adverse remodeling and increase in contractility through global
      cardiomyocyte transduction for maximal efficacy. This article will review a
      variety of gene-transfer strategies in models of coronary artery disease and HF
      and discuss the relative success of these strategies in improving the efficiency
      of vector-mediated cardiac gene delivery.

PMID- 22418065
TI  - A novel intranasal therapy of azelastine with fluticasone for the treatment of
      allergic rhinitis.
AB  - BACKGROUND: Moderate-to-severe allergic rhinitis (AR) is a challenge to treat,
      with many patients using multiple therapies and achieving limited symptom
      control. More effective therapies must be developed and tested in well
      controlled, randomized, prospective studies with a direct comparison to current
      standards. OBJECTIVES: The aim of these studies was to investigate the efficacy
      of MP29-02 (a novel formulation of azelastine and fluticasone propionate [FP]) in
      patients with moderate-to-severe seasonal allergic rhinitis (SAR) and to compare
      its efficacy with 2 first-line therapies (ie, intranasal azelastine and
      intranasal FP) in this population. METHODS: Three thousand three hundred ninety
      eight patients (>=12 years old) with moderate-to-severe SAR were enrolled into 3
      multicenter, randomized, double-blind, placebo- and active-controlled, parallel
      group trials (MP4002 [NCT00651118], MP4004 [NCT00740792], and MP4006
      [NCT00883168]). Each trial was conducted for 14 days during different allergy
      seasons. The primary efficacy variable was the sum of the morning and evening
      change from baseline in reflective total nasal symptom score (range, 0-24) over
      the treatment period. Outcomes for the meta-analysis included efficacy according
      to disease severity and time to response in relevant responder criteria. RESULTS:
      In the meta-analysis MP29-02 reduced the mean reflective total nasal symptom
      score from baseline (-5.7 [SD, 5.3]) more than FP (-5.1 [SD, 4.9], P < .001),
      azelastine (-4.4 [SD, 4.8], P < .001), or placebo (-3.0 [SD, 4.2], P < .001).
      This benefit was observed from the first day of assessment, with improvement in
      each individual nasal symptom, even in the patients with the most severe disease.
      MP29-02 achieved response consistently days earlier and showed greater efficacy
      in patients with moderate-to-severe rhinitis than FP and azelastine. CONCLUSIONS:
      MP29-02 represents a novel therapy that demonstrated superiority to 2 first-line
      therapies for AR. Patients with moderate-to-severe SAR achieved better control,
      and their symptoms were controlled earlier with MP29-02 than with recommended
      medications according to guidelines.

PMID- 22418066
TI  - Reduced expression of the prostaglandin E2 receptor E-prostanoid 2 on bronchial
      mucosal leukocytes in patients with aspirin-sensitive asthma.
AB  - BACKGROUND: Prostaglandin E(2) (PGE(2)) is thought to play a role in the
      pathogenesis of aspirin-sensitive asthma (ASA). OBJECTIVE: We sought to extend
      our previous observations implicating impaired inflammatory cell responsiveness
      to PGE(2) as a pathogenetic mechanism in patients with aspirin-sensitive
      rhinosinusitis to the bronchial mucosa in patients with ASA. METHODS:
      Immunohistochemistry was used to enumerate inflammatory cells and their
      expression of cysteinyl leukotriene receptors 1 and 2 (CysLT(1) and CysLT(2)) and
      the PGE(2) receptors E-prostanoid 1 to 4 (EP(1)-EP(4)) in bronchial biopsy
      specimens from patients with ASA, patients with aspirin-tolerant asthma, and
      control subjects (n= 15 in each group). Concentrations of PGE(2) in
      bronchoalveolar lavage fluid were measured by using ELISA. The effects of PGE(2)
      and EP receptor agonists on CD3/CD28-stimulated cytokine production by PBMCs were
      measured by using ELISA. Airways responsiveness to LTD(4)in vivo was measured in
      asthmatic patients by means of bronchial challenge. RESULTS: Compared with
      patients with aspirin-tolerant asthma, patients with ASA had increased bronchial
      mucosal neutrophil and eosinophil numbers but reduced percentages of T cells,
      macrophages, mast cells, and neutrophils expressing EP(2). Both groups showed
      increased bronchial sensitivity to inhaled LTD(4), but this did not correlate
      with mucosal expression of CysLT(1) or CysLT(2). Bronchoalveolar lavage fluid
      PGE(2) concentrations were comparable in all groups. In vitro PGE(2) inhibited
      cytokine production by PBMCs through EP(2) but not other PGE(2) receptors.
      CONCLUSION: Our data are consistent with the hypothesis that impaired inhibition
      of inflammatory leukocytes by PGE(2) acting through the EP(2) receptor has a role
      in the pathogenesis of ASA.

PMID- 22418067
TI  - The role of microglia at synapses in the healthy CNS: novel insights from recent
      imaging studies.
AB  - In the healthy brain, quiescent microglia continuously remodel their shape by
      extending and retracting highly motile processes. Despite a seemingly random
      sampling of their environment, microglial processes specifically interact with
      subsets of synaptic structures, as shown by recent imaging studies leading to
      proposed reciprocal interactions between microglia and synapses under non
      pathological conditions. These studies revealed that various modalities of
      microglial dynamic behavior including their interactions with synaptic elements
      are regulated by manipulations of neurotransmission, neuronal activity and
      sensory experience. Conversely, these observations implied an unexpected role for
      quiescent microglia in the elimination of synaptic structures by specialized
      mechanisms that include the phagocytosis of axon terminals and dendritic spines.
      In light of these recent discoveries, microglia are now emerging as important
      effectors of neuronal circuit reorganization.

PMID- 22418068
TI  - Cytochrome P450 (CYP) in fish.
AB  - Cytochrome P450 (CYP) enzymes are members of the hemoprotein superfamily, and are
      involved in the mono-oxygenation reactions of a wide range of endogenous and
      exogenous compounds in mammals and plants. Characterization of CYP genes in fish
      has been carried out intensively over the last 20 years. In Japanese pufferfish
      (Takifugu rubripes), 54 genes encoding P450s have been identified. Across all
      species of fish, 137 genes encoding P450s have been identified. These genes are
      classified into 18 CYP families: namely, CYP1, CYP2, CYP3, CYP4, CYP5, CYP7,
      CYP8, CYP11, CYP17, CYP19, CYP20, CYP21, CYP24, CYP26, CYP27, CYP39, CYP46 and
      CYP51.We pinpointed eight CYP families: namely, CYP1, CYP2, CYP3, CYP4, CYP11,
      CYP17, CYP19 and CYP26 in this review because these CYP families are studied in
      detail. Studies of fish P450s have provided insights into the regulation of P450
      genes by environmental stresses including water pollution. In this review, we
      present an overview of the CYP families in fish.

PMID- 22418069
TI  - Effects of Ibuprofen on hematological, biochemical and enzymological parameters
      of blood in an Indian major carp, Cirrhinus mrigala.
AB  - In the present investigation, the most commonly used pharmaceutical drug
      Ibuprofen (IB) was exposed to an Indian major carp Cirrhinus mrigala under static
      bioassay method to estimate its toxicological effects for a period of 35 days.
      The median lethal concentration (LC 50) of IB to the fish C. mrigala for 24h was
      found to be 142 ppm. In sublethal treatment (1/10th of LC 50 24h value, 14.2
      ppm), a significant decrease in erythrocyte (RBC), mean cellular hemoglobin
      concentration (MCHC) and plasma protein levels were observed throughout the study
      period when compare to that of their respective controls. In contrast,
      haemoglobin (Hb), hematocrit (Hct), mean cellular volume (MCV), mean cellular
      hemoglobin (MCH), leucocyte (WBC), plasma glucose and alanine transaminase (ALT)
      levels were increased in this study period. On the other hand, a mixed trend was
      noticed in aspartate aminotransaminase (AST) enzyme activity. Alterations of
      these parameters can be effectively used as potential biomarkers in monitoring of
      IB toxicity in the aquatic organisms. However, more detailed studies on these
      specific biomarkers are needed to assess the impacts of human pharmaceutical
      drugs in the field of pharmacotoxicology and aquatic toxicology.

PMID- 22418070
TI  - Determination of landiolol, an ultra-short-acting beta1-receptor antagonist, in
      human plasma by liquid chromatography-tandem mass spectrometry.
AB  - A method for the determination of landiolol, an ultra-short-acting beta1
      adrenoreceptor antagonist, in human plasma has been developed and validated. With
      the addition of pyridostigmine bromide to stabilize landiolol in the blood/plasma
      samples, and bisoprolol as internal standard, plasma samples were subjected to
      liquid-liquid extraction with diethyl ether:dicholoromethane (60:40, v/v) prior
      to assay by liquid chromatography-tandem mass spectrometry. Separation was
      performed on a TC-C18 column (150 mm * 4.6 mm, 5 MUm) using a mobile phase of
      methanol:10 mM ammonium acetate containing 1% formic acid (65:35, v/v) in a run
      time of 3.5 min. Detection involved electrospray ionization in the positive ion
      mode followed by multiple reaction monitoring of the precursor-to-product ion
      transitions of landiolol at m/z 510.1->157.2 and bisoprolol at m/z 326.3->116.1.
      The method was linear over the concentration range 0.5-500 ng/ml with a lower
      limit of quantitation of 0.5 ng/ml. Intra- and inter-day precisions (as relative
      standard deviation, RSD) were <4.4% and <10.0%, respectively, with accuracy (as
      relative error, RE) <10.0%. The method was successfully applied to a clinical
      pharmacokinetic study involving a continuous infusion of landiolol hydrochloride
      to healthy Chinese volunteers.

PMID- 22418071
TI  - Quantitative determination of oseltamivir and oseltamivir carboxylate in human
      fluoride EDTA plasma including the ex vivo stability using high-performance
      liquid chromatography coupled with electrospray ionization tandem mass
      spectrometry.
AB  - Oseltamivir, the ethyl ester prodrug of the neuramidase inhibitor oseltamivir
      carboxylate, is licensed for the treatment of patients with influenza virus
      infection. Here we describe the development and validation of an assay for the
      simultaneous quantification of oseltamivir and oseltamivir carboxylate in human
      fluoride EDTA plasma including the ex vivo stability using liquid chromatography
      coupled to tandem mass spectrometry. Sample pretreatment consisted of protein
      precipitation with 8% (v/v) trichloroacetic acid in water using only 50 MUL
      plasma. Chromatographic separation was performed on a reversed phase C18 column
      (150 mm * 2.0 mm ID, particle size 4 MUm) with a stepwise gradient using 0.1%
      formic acid and methanol at a flow rate of 250 MUL/min. A triple quadrupole mass
      spectrometer operating in the positive ionization mode was used for detection and
      drug quantification. The method was validated over a range of 3-300 ng/mL for
      oseltamivir and 10-10,000 ng/mL for oseltamivir carboxylate. Deuterated
      oseltamivir and oseltamivir carboxylate were used as internal standards. The
      intra-assay accuracies and precisions for oseltamivir were between -8.8 and 16.3%
      at the LLOQ level, whereas for all other concentration levels this was -8.6 and
      14.5%. For oseltamivir carboxylate the intra-assay accuracies and precisions were
      between -10.9 and 10.7% at all levels. Furthermore, oseltamivir was stable in
      plasma and whole blood ex vivo in commercially available fluoride EDTA tubes for
      at least 24h at 2-8  degrees C. This method is now applied for the determination
      of both compounds in specific patient populations to evaluate current dosing
      guidelines.

PMID- 22418072
TI  - Simultaneous determination of pimpinellin, isopimpinellin and phellopterin in rat
      plasma by a validated UPLC-MS/MS and its application to a pharmacokinetic study
      after administration of Toddalia asiatica extract.
AB  - A rapid and selective ultra performance liquid chromatography-tandem mass
      spectrometry (UPLC-MS/MS) method was developed for simultaneous determination of
      three bioactive coumarins of Toddalia asiatica extract including pimpinellin,
      isopimpinellin and phellopterin in rat plasma for the first time. Phenacetin was
      used as the internal standard (IS). Plasma samples were extracted by liquid
      liquid extraction with methyl tert-butyl ether. The chromatographic separation
      was carried out on an ACQUITY UPLCTM BEH C18 column with an isocratic mobile
      phase consisting of methanol-5 mmol/L ammonium acetate (65:35, v/v). The
      detection was performed on a triple quadrupole tandem mass spectrometer by
      multiple reaction monitoring (MRM) via electrospray ionization (ESI) source with
      positive ionization mode. The method was linear for all analytes over
      investigated range with all correlation coefficients greater than 0.9942. The
      lower limits of quantification (LLOQ) were 25.0 ng/mL for pimpinellin, 10.0 ng/mL
      for isopimpinellin and 5.00 ng/mL for phellopterin. The intra- and inter-day
      precision (RSD%) was within 12% and the accuracy (RE%) ranged from -2.3% to 5.5%.
      The rapid and sensitive method was fully validated and successfully applied to
      the pharmacokinetic study of pimpinellin, isopimpinellin and phellopterin in rats
      following oral administration of Toddalia asiatica extract.

PMID- 22418073
TI  - Transnasal endoscopic repair of choanal atresia in a tertiary care centre: a
      review of outcomes.
AB  - INTRODUCTION/AIM: Choanal atresia (CA) is an obliteration, in newborns, of the
      airway at the level of posterior nasal aperture resulting in absence of
      connection between the nasal cavity and the aerodigestive tract. It is rare, with
      incidence of 1 in 7000 live births. This review is aimed at assessing the factors
      influencing the outcome of transnasal endoscopic repair of CA in a tertiary
      referral children's hospital. MATERIAL/METHOD: A retrospective study was carried
      out between 2002 and 2009. 31 children; 14 boys and 17 girls, age range 1 day to
      15 years, mean 23.4 months were included. Unilateral presentation was 19 (11
      right, 8 left) and bilateral was 12. All patients had transnasal endoscopic
      repair under direct vision. Nasal stents were placed for varying duration (range
      4-12 weeks) or nasopharyngeal airways (removed within 24h) were inserted at time
      of surgery. Patients were monitored for re-stenosis and revisions carried out as
      necessary, with a mean follow-up of 11.9 months. RESULTS: 54.7% (n=17) of
      patients had re-stenosis requiring revision surgery. Of these, 41.1% (n=7) had
      success after the 1st revision, 20% had success after the 2nd revision while
      12.3% had success after the 3rd revision. One patient required more than four
      revisions. 80% of re-stenosis requiring revisions occurred in children who had
      surgery under 10 months of age and of these, approx. 42% were 1-week-old or
      younger. 57% of those who had stents for 4-6 weeks (n=15) had re-stenosis
      requiring revision while only 33.3% of those who either had no stents or had NP
      airways removed within 24h (n=16) had re-stenosis (P=0.019). The re-stenosis rate
      was comparable for those who had mitomycin (53%) versus those who did not (60%).
      CONCLUSION: Transnasal endoscopic repair of CA is effective and safe and provides
      the benefit of surgery under direct vision. Age 1 week or less was a predictive
      factor for re-stenosis. Intranasal stents was also associated with increased
      incidence of re-stenosis and the use of mitomycin C does not seem to have any
      significant effect on re-stenosis.

PMID- 22418074
TI  - The effect of cochlear implantation in development of intelligence quotient of 6
      9 deaf children in comparison with normal hearing children (Iran, 2009-2011).
AB  - OBJECTIVE: Before the introduction of cochlear implant (CI) in 1980, hearing aids
      were the only means by which profoundly deaf children had access to auditory
      stimuli. Nowadays, CI is firmly established as effective option in speech and
      language rehabilitation of deaf children, but much of the literature regarding
      outcomes for children after CI are focused on development of speech and less is
      known about language acquisition. So, the main aim of this study is the
      evaluation of verbal intelligence quotient (IQ) of cochlear implanted children in
      comparison with normal children. METHODS AND MATERIALS: 30 cochlear implanted and
      30 normal hearing children with similar socio-economic level at the same age were
      compared by a revised version (in Persian) of WISC test (Wechsler, 1991). Then
      the data were analyzed through SPSS software 16. RESULTS: In spite of the fact
      that cochlear implanted children did well in different parameters of WISC test,
      the average scores of this group was less than normal hearing children. But in
      similarities (one of the parameters of WISC test) 2 group's performance was
      approximately the same. CONCLUSION: CI plays an important role in development of
      verbal IQ and language acquisition of deaf children. Different researches
      indicate that most of the cochlear implanted children show less language delay
      during the time.

PMID- 22418075
TI  - Characterization of lipid model membranes designed for studying impact of
      ceramide species on drug diffusion and penetration.
AB  - The stratum corneum (SC) intercellular lipid matrix plays a crucial role in the
      skin barrier function. In the present study, lipid model membranes mimicking its
      phase behavior were prepared and characterized using different analytical
      techniques (i.a. SAXD, HPTLC, ESEM, confocal Raman imaging, ATR-FTIR
      spectroscopy) in order to obtain well-standardized model membranes for diffusion
      and penetration studies. The lipid model membranes should be used in the future
      for studying the impact of each ceramide species on the diffusion and penetration
      of drugs. The SAXD study confirmed that the lipids within artificial lipid
      systems are arranged similarly to the lipids in the human SC. The polarization
      microscopic and ESEM images showed the homogenous deposition of lipids on the
      polycarbonate filter. Both the HPTLC and confocal Raman imaging studies proved
      the homogenous distribution of individual lipid classes within the lipid model
      membranes. First in vitro diffusion experiments (performed using an ATR-FTIR
      diffusion cell) of the hydrophilic compound, urea, revealed that the lipid model
      membrane represents even stronger diffusion barrier than the human SC.

PMID- 22418076
TI  - New times, new trends for ethionamide: In vitro evaluation of drug-loaded
      thermally carbonized porous silicon microparticles.
AB  - Multidrug-resistant tuberculosis (MDR-TB) has become a worldwide problem and a
      major public health concern. The mechanisms of resistance are fairly well
      characterized for most agents, but MDR limits the therapeutic usefulness of both
      new and classical medicines against TB. Ethionamide (ETA) is a thioamide
      antibiotic and one of the most widely used drugs as second line agent for the
      treatment of MDR-TB. Over the years, some studies have emerged to improve the
      bioavailability of this drug and of its active metabolites. However, inactive
      metabolites of ETA are still a major drawback in its application against TB.
      Porous silicon (PSi) materials can be applied to improve the dissolution behavior
      of poorly water-soluble compounds and to overcome toxicity and other drug-related
      problems in oral delivery. In the present work, we have loaded ETA into thermally
      carbonized-PSi (TCPSi) microparticles and studied the solubility, toxicity,
      permeability, and metabolic profiles of the PSi-loaded drug. The solubility and
      permeability of ETA was clearly enhanced after loaded into TCPSi particles at
      different pH-values. ETA was in general toxic at concentrations above 0.50mM to
      HepG2, Caco-2, and RAW macrophage cells, but the toxicity was drastically reduced
      when the drug was loaded into the microparticles. ETA showed a fast
      metabolization process in the presence of the TCPSi particles. In addition, new
      thiolated metabolites were identified from incubation of ETA-loaded PSi with
      HepG2 liver cells, which opens new perspectives toward both the understanding of
      ETA metabolism and the development of novel ETA-based systems with improved
      efficacy against MDR-TB.

PMID- 22418077
TI  - Positional changes of the masseter and medial pterygoid muscles after surgical
      mandibular advancement procedures: an MRI study.
AB  - This study evaluated whether surgical mandibular advancement procedures induced a
      change in the direction and the moment arms of the masseter (MAS) and medial
      pterygoid (MPM) muscles. Sixteen adults participated in this study. The sample
      was divided in two groups: Group I (n=8) with a mandibular plane angle (mpa) <39
      degrees  and Group II (n=8) with an mpa >39 degrees . Group I patients were
      treated with a bilateral sagittal split osteotomy (BSSO). Those in Group II were
      treated with a BSSO combined with a Le Fort I osteotomy. Pre- and postoperative
      direction and moment arms of MAS and MPM were compared in these groups.
      Postsurgically, MAS and MPM in Group II showed a significantly more vertical
      direction in the sagittal plane. Changes of direction in the frontal plane and
      changes of moment arms were insignificant in both groups. This study demonstrated
      that bimaxillary surgery in patients with an mpa >39 degrees  leads to a
      significant change of direction of MAS and MPM in the sagittal plane.

PMID- 22418078
TI  - Increased expression of graft intraepithelial T-cell pro-inflammatory cytokines
      compared with native lung during episodes of acute rejection.
AB  - BACKGROUND: We have previously reported that T-cell pro-inflammatory cytokines in
      the airways are associated with acute lung transplant rejection. However, during
      acute rejection episodes, we found no significant differences in airway
      intraepithelial T cell pro-inflammatory cytokines from stable and rejecting
      patients due to broad cytokine variability between patient groups. To overcome
      this limitation, we hypothesized that there would be an increase in pro
      inflammatory intraepithelial T-cells in the graft compared with native airway
      during acute rejection. METHODS: Bronchial brushings from patients with stable
      graft function, evidence of acute rejection, bronchiolitis obliterans syndrome,
      infection, and healthy controls were stimulated and pro-inflammatory cytokines in
      intraepithelial T cells from graft and native airway were determined using
      multiparameter flow cytometry. RESULTS: There was a significant increase in
      intraepithelial T-cell interferon-gamma and tumor necrosis factor (TNF)-alpha in
      the graft of patients with acute rejection compared with intraepithelial T cells
      obtained from the native airway, but no changes were noted among other patient
      groups. The increase in intraepithelial T-cell TNF-alpha was more pronounced the
      higher the acute rejection grade. CONCLUSIONS: The graft airway epithelium is
      enriched with T cells producing interferon-gamma and TNF-alpha during acute graft
      rejection. Therapeutic targeting of these pro-inflammatory cytokines and improved
      monitoring using this assay may reduce acute lung transplant rejection.

PMID- 22418079
TI  - Influence of donor and recipient sex mismatch on heart transplant outcomes:
      analysis of the International Society for Heart and Lung Transplantation
      Registry.
AB  - BACKGROUND: Prior studies have presented contradictory results after analyzing
      associations between donor and recipient sex on survival after heart
      transplantation and causes of death such as acute rejection (AR) and cardiac
      allograft vasculopathy (CAV). We used the International Society for Heart and
      Lung Transplantation (ISHLT) Registry, the largest repository of heart transplant
      outcomes worldwide, to comprehensively address these questions. METHOD: We
      studied 60,584 adult recipients of heart transplants performed between 1990 and
      2008. Outcomes of interest were overall survival, death-censored allograft
      survival, AR, and CAV, which were studied using regression models. To assess
      whether donor/recipient sex mismatch affected outcomes, the experience of male
      recipients with female vs male donors was compared with that of female recipients
      with female vs male donors through inclusion of an interaction term between donor
      and recipient sex. RESULTS: Significant differences were observed between male
      and female recipients in overall survival and death-censored allograft survival
      for female vs male donors. Male recipients of female allografts had a 10%
      increase in adjusted mortality relative to male recipients of male allografts,
      whereas female recipients of female allografts had a 10% decrease in adjusted
      mortality relative to female recipients of male allografts (p < 0.0001). Findings
      were similar for death-censored allograft survival. Differences in the effect of
      donor sex on AR or CAV between male and female recipients were not significant.
      CONCLUSIONS: Analysis of the ISHLT data set has demonstrated a strong association
      between donor/recipient sex mismatch and reduced survival after heart
      transplantation.

PMID- 22418081
TI  - Methanosarcina: the rediscovered methanogen for heavy duty biomethanation.
AB  - Anaerobic digestion is an important technology in the framework of renewable
      energy production. The anaerobic digestion system is susceptible to perturbations
      due to the sensitivity of the methanogens towards environmental factors.
      Currently, technology is evolving from conventional waste treatment, i.e. the
      removal of pollutants, to very intensive biogas production from concentrated
      wastes, in the framework of bio-energy production. In the latter configuration
      Methanosarcina species appear to be of crucial importance. Methanosarcina sp.
      are, compared to other methanogens, quite robust towards different impairments.
      They are reported to be tolerant to total ammonium concentrations up to 7000 mg
      L(-1), salt concentrations up to 18,000 mg Na(+)L(-1), a pH shock of 0.8-1.0
      units and acetate concentrations up to 15,000 mg CODL(-1). The possibilities of
      Methanosarcina sp. as key organisms in specific types of anaerobic digestion
      systems are demonstrated in this review.

PMID- 22418080
TI  - Development of a process for the production of L-amino-acids concentrates from
      microalgae by enzymatic hydrolysis.
AB  - A process for the production of l-amino-acids concentrates from microalgae
      biomass by enzymatic hydrolysis has been developed. The process includes pre
      treatment for cell-disruption, enzymatic hydrolysis and final separation by
      centrifugation. Thermal and mechanical cell-disruption methods have been tested,
      selecting mechanical disruption using bead milling for 30 min. The enzymatic
      hydrolysis was done using the commercial enzymes Alcalase and Flavourzyme.
      Maximum hydrolysis was obtained for biomass concentrations under 270 g/l and
      previous additional treatment with Viscozyme, reaching a 42% hydrolysis. Repeated
      reaction steps increased the hydrolysis from 42% (4h) with a single step to 59%
      (8h) after two successive steps. Further increase of the number of steps had a
      meagre impact on the global yield. The process widens the portfolio of products
      that can be obtained from microalgae biomass and is a new possibility to enhance
      the economic viability of microalgae-based biofuels production processes.

PMID- 22418082
TI  - Methane production from horse manure and stall waste with softwood bedding.
AB  - Substantial stall waste is generated from horses on softwood bedding. The methane
      potential (G(pot)) of horse manure and constructed mixtures of stall waste with
      softwood bedding was determined at 35 degrees C. G(pot) of 68, 191 and 273 mL/g
      volatile solids (VS) were estimated for three separate batches of horse manure,
      indicating variability in the material. Cumulative energy production over 20-40
      days ranged from 3.11 +/- 0.92 to 8.45 +/- 5.42 * 10(5)kJ/metric ton wet weight
      horse manure alone, and from 1.69 +/- 0.39 to 3.91 +/- 0.47 * 10(5)kJ/metric ton
      wet weight horse manure plus softwood stall bedding (mixed at a 1:1 ratio on a VS
      basis). Softwood bedding was barely degradable and diluted the energy production
      of the stall waste; however, it did not cause inhibition of methane production
      from manure. Manually separated used softwood bedding contained substantial
      methane potential.

PMID- 22418083
TI  - Ultrasound-assisted alkaline pretreatment of sugarcane bagasse for fermentable
      sugar production: optimization through response surface methodology.
AB  - Ultrasound-assisted alkaline pretreatment of sugarcane bagasse (SCB) for
      fermentable sugar production was carried out and the influence of particle size,
      liquid to solid ratio (LSR), NaOH concentration, temperature and sonication time
      on delignification and reducing sugar production was ascertained with Placket
      Burman design. The best combination of each significant factor was determined by
      a central composite design (CCD) and optimum pretreatment conditions for maximum
      reducing sugar yield (96.27%) were particle size of 0.27 mm, LSR of 25 ml/g, NaOH
      concentration of 2.89% (w/v), temperature of 70.15 degrees C and pretreatment
      time of 47.42 min. Under these conditions, 92.11% of theoretical reducing sugar
      yield was observed experimentally. The substantial reduction in pretreatment time
      and temperature with improved efficiency is the most attractive features of the
      ultrasound-assisted alkaline pretreatment.

PMID- 22418084
TI  - Production of lipopeptides by Bacillus amyloliquefaciens XZ-173 in solid state
      fermentation using soybean flour and rice straw as the substrate.
AB  - This work was aimed to produce lipopeptides by Bacillus amyloliquefaciens XZ-173
      in solid state fermentation using agro-industrial byproducts. A central composite
      design was used to get the highest lipopeptides production. Results revealed that
      the optimal conditions for maximum lipopeptides production were 1.79% starch and
      1.91% yeast extract by employing 5.58 g soybean flour and 3.67 g rice straw as
      the solid substrate with initial pH 7.5, moisture content 55% and a 10% inoculum
      level at 30 degrees C for 2 days. Under these conditions, the experimental yield
      of lipopeptides reached 50.01 mg/gds, which was very close to the predicted value
      (49.91 mg/gds). At high concentration, the lipopeptides extracted from fermented
      substrates showed strong antibiotic activity against Rhizoctonia solani and
      Ralstonia solanacearum and certain emulsification but good emulsion stability.
      This is the first report on lipopeptides production that uses rice straw as a
      major substrate.

PMID- 22418085
TI  - Chiasmal stroke in patient with atrial fibrillation and complete occlusion of
      right internal carotid artery.

PMID- 22418086
TI  - Reversible prolonged bilateral inferior altitudinal visual field defects
      associated with migraine.
AB  - A 14-year-old girl with a history of migraine headaches and methylphenidate use
      presented with 2 episodes of prolonged but completely reversible inferior
      altitudinal homonymous visual field loss, lasting 5 days and 4.5 weeks,
      respectively. Neuroimaging studies were unremarkable. We discuss the potential
      causes of our patient's visual symptoms and speculate and hypothesize that it may
      represent an atypical manifestation of migraine, perhaps related to a
      channelopathy.

PMID- 22418087
TI  - Pursuit-paretic and epileptic nystagmus in MELAS.
AB  - A 27-year-old man with MELAS 3243 mutation developed a right homonymous
      hemianopia, left beating nystagmus, and impaired smooth pursuit (SP) to the left.
      Intermittently, the left beating nystagmus changed to right beating with
      rightward eye and head deviation and associated altered mental status. Each
      episode lasted several minutes. MRI revealed restricted diffusion in left parieto
      temporo-occipital cortices. During the ictus, electroencephalogram showed
      epileptic discharges in the left temporo-occipital region, and single photon
      emission computed tomography demonstrated hyperperfusion in the same area. The
      interictal left beating nystagmus may be ascribed to contralesional bias of SP
      imbalance since the parieto-temporo-occipital region is involved in the
      generation of SP. The ictal right beating nystagmus and rightward head and eye
      deviation indicate coactivation of the SP areas and parietal eye field. This
      report documents the novel co-occurrence of pursuit-paretic and epileptic
      nystagmus.

PMID- 22418088
TI  - Maternal choline intake modulates maternal and fetal biomarkers of choline
      metabolism in humans.
AB  - BACKGROUND: In 1998 choline Adequate Intakes of 425 and 450 mg/d were established
      for nonpregnant and pregnant women, respectively. However, to our knowledge, no
      dose-response studies have been conducted to evaluate the effects of pregnancy or
      maternal choline intake on biomarkers of choline metabolism. OBJECTIVE: We sought
      to quantify the effects of pregnancy and maternal choline intake on maternal and
      fetal indicators of choline metabolism. DESIGN: Healthy pregnant (n = 26; 27 wk
      gestation) and nonpregnant (n = 21) women were randomly assigned to receive 480
      or 930 mg choline/d for 12 wk. Fasting blood samples and placental tissue and
      umbilical cord venous blood were collected and analyzed for choline and its
      metabolites. RESULTS: Regardless of the choline intake, pregnant women had higher
      circulating concentrations of choline (30%; P < 0.001) but lower concentrations
      of betaine, dimethylglycine, sarcosine, and methionine (13-55%; P < 0.001).
      Obligatory losses of urinary choline and betaine in pregnant women were ~2-4
      times as high (P <= 0.02) as those in nonpregnant women. A higher choline intake
      yielded higher concentrations of choline, betaine, dimethylglycine, and sarcosine
      (12-46%; P <= 0.08) in both pregnant and nonpregnant women without affecting
      urinary choline excretion. The higher maternal choline intake also led to a
      doubling of dimethylglycine in cord plasma (P = 0.002). CONCLUSION: These data
      suggest that an increment of 25 mg choline/d to meet the demands of pregnancy is
      insufficient and show that a higher maternal choline intake increases the use of
      choline as a methyl donor in both maternal and fetal compartments. This trial was
      registered at clinicaltrials.gov as NCT01127022.

PMID- 22418090
TI  - A fungal-like organism associated with a wasp (Hymenoptera: Pteromalidae) in
      Dominican amber.
AB  - A fungal-like organism emerging from a parasitic wasp (Hymenoptera: Pteromalidae)
      in Dominican amber is characterized. The fossil consists of a white sclerotium
      like formation in the wasp's abdomen and a flattened clava-like structure with an
      ovoid terminus emerging from the sclerotium-like formation. The ovoid terminus
      bears a protruding elliptical appendix. The fossil, which is characterized by its
      small size, somatic configuration, pteromalid host and presence in Dominican
      amber, cannot be placed with assurance in any extant fungal group at this time.

PMID- 22418089
TI  - A changing pattern of childhood BMI growth during the 20th century: 70 y of data
      from the Fels Longitudinal Study.
AB  - BACKGROUND: The BMI distribution shifted upward in the United States between the
      1960s and the 1990s, but little is known about secular trends in the pattern of
      BMI growth, particularly earlier in the century and early in childhood.
      OBJECTIVE: The objective was to examine differences in BMI growth in children
      born in 1929-1999. DESIGN: BMI curves from ages 2 to 18 y were produced for 855
      European-American children in the Fels Longitudinal Study born in 1929-1953, 1954
      1972, and 1973-1999. Age (A(min)) and BMI (BMI(min)) at adiposity rebound and age
      (AV(max)), BMI (BMIV(max)), and velocity (V(max)) at maximum velocity were
      derived; multivariable regression was used to examine whether maternal BMI,
      infant weight gain, and other covariates mediated the cohort effects on these
      traits. RESULTS: BMI curves showed that children born in 1973-1999 had the lowest
      BMI values until age 5 y but had the largest values from age 8 y onward. In
      adjusted models, boys and girls born in 1973-1999 had a 0.15-kg/m(2) per year
      faster V(max) and a 1-kg/m(2) higher BMIV(max) than did children of the same sex
      born in 1929-1953, and girls had a 0.8-y earlier A(min) (P < 0.01). Maternal BMI
      and infant weight gain were associated with an obesity-prone pattern of BMI
      growth but did not account for the observed trends. CONCLUSIONS: Shifts in the
      BMI growth rate around the time of pubertal initiation were apparent starting
      after 1973. The BMI growth curve did not increase monotonically over time;
      rather, children born during the obesity epidemic were characterized by lower BMI
      values before the adiposity rebound and by rapid subsequent BMI gain.

PMID- 22418091
TI  - Mycoplasma pneumoniae bronchiolitis mimicking asthma in an adult.

PMID- 22418092
TI  - A novel galactofuranan from the cell wall of Arthrobacter sp. VKM As-2576.
AB  - The investigated cell wall polysaccharide of Arthrobacter sp. VKM Ac-2576 (phylum
      Actinobacteria) is a (1->6)-linked beta-D-galactofuranan with the alpha-D
      GlcpNAc3NAc residues that glycosylate virtually all (~90%) hydroxyl groups at C-2
      of galactose. Its repeating unit has the following structure: ->6)D-beta-Galf-(1
      >2) ? alpha-D-GlcpNAc3NAc-(1 (90%). The structure of the polysaccharide was
      established by chemical and NMR spectroscopic methods; it is identified for the
      first time.

PMID- 22418093
TI  - Multigram-scale synthesis of an orthogonally protected 2-acetamido-4-amino-2,4,6
      trideoxy-D-galactose (AAT) building block.
AB  - Reported is the gram-scale synthesis of tert-butyldiphenylsilyl 4-(N
      benzyloxycarbonyl)-amino-2-azido-2,4,6-trideoxy-beta-D-galactopyranoside, which
      represents an orthogonally protected 2,4-diamino-D-fucose building block, a
      common constituent of various zwitterionic polysaccharides. The building block
      has been synthesized from D-glucosamine in 19% overall yield over 14 steps,
      requiring 5 chromatographic purifications. The key step in the synthesis is the
      introduction of the C-4 amino substituent, which has been accomplished by a one
      pot three step procedure, involving regioselective C-3-O-trichloroacetimidate
      formation, C-4-O-triflation, and intramolecular substitution. The building block
      can be used as an acceptor and is readily transformed into a donor glycoside.

PMID- 22418094
TI  - Rice BGlu1 glycosynthase and wild type transglycosylation activities
      distinguished by cyclophellitol inhibition.
AB  - The rice BGlu1 beta-D-glucosidase nucleophile mutant E386G is a glycosynthase
      that catalyzes the synthesis of cellooligosaccharides from alpha-d-glucopyranosyl
      fluoride (GlcF) donor and p-nitrophenyl (pNP) cellobioside (Glc2-pNP) or cello
      oligosaccharide acceptors. When activity with other donors and acceptors was
      tested, the initial enzyme preparation cleaved pNP-beta-D-glucopyranoside (Glc
      pNP) and pNP-beta-D-fucopyranoside (Fuc-pNP) to pNP and glucose and fucose,
      suggesting contamination with wild type BGlu1 beta-glucosidase. The products from
      reaction of GlcF and Fuc-pNP included Fuc-beta-(1->3)-Fuc-pNP, Glc-beta-(1->3)
      Fuc-pNP, and Fuc-beta-(1->4)-Glc-beta-(1->3)-Fuc-pNP, suggesting the presence of
      both wild type BGlu1 and its glycosynthase. Inhibition of the BGlu1 beta
      glucosidase activity within this preparation by cyclophellitol confirmed that the
      E386G glycosynthase preparation was contaminated with wild type BGlu1. Rice BGlu1
      E386G-2, generated from a new construct designed to minimize back-mutation,
      showed glycosynthase activity without wild type hydrolytic or transglycosylation
      activity. E386G-2 catalyzed transfer of glycosyl residues from GlcF, alpha-L
      arabinosyl fluoride, alpha-D-fucosyl fluoride, alpha-D-galactosyl fluoride, alpha
      D-mannosyl fluoride, and alpha-D-xylosyl fluoride donors to Glc2-pNP acceptor.
      The synthetic products from the reactions of alpha-fucosyl fluoride and alpha
      mannosyl fluoride donors were confirmed to result from addition of a beta-(1->4)
      linked glycosyl residue. Moreover, the E386G glycosynthase transferred glucose
      from GlcF donor to glucose, cellobiose, Glc-pNP, Fuc-pNP, pNP-beta-D
      galactopyranoside, and pNP-beta-D-xylopyranoside acceptors, but little to pNP
      beta-D-mannopyranoside. Production of longer oligosaccharides occurred most
      readily on acceptors with an equatorial 4-OH. Elimination of wild type
      contamination thereby allowed a clear assessment of BGlu1 E386G glycosynthase
      catalytic abilities.

PMID- 22418095
TI  - An integrated microparticle sorting system based on near-field optical forces and
      a structural perturbation.
AB  - We demonstrate an integrated microparticle passive sorting system based on the
      near-field optical forces exerted by a 3-dB optical splitter that consists of a
      slot waveguide and a conventional channel waveguide. We show that 320 nm and 2 um
      polystyrene particles brought into the splitter are sorted so that they exit
      along the slot waveguide and channel waveguide, respectively. Electromagnetic
      simulations and precise position tracking experiments are carried out to
      investigate the sorting mechanism. As the waveguides are separated by 200 nm,
      they provide two potential wells for the smaller particles, but only one broad
      potential well for the larger particles, since their diameters exceed the
      distance between the two field maxima. A structural perturbation consisting of a
      stuck bead transfers the smaller particles to the second well associated with the
      slot waveguide, while the larger particles are brought to the region between the
      two waveguides and eventually follow the channel waveguide, as it is associated
      with a deeper potential well. This label-free passive particle sorting system
      requires low guided power (20 mW in these experiments), and provides a new
      technique for sorting sub-micron particles.

PMID- 22418096
TI  - Phase retrieval from single biomolecule diffraction pattern.
AB  - In this paper, we propose the SPR (sparse phase retrieval) method, which is a new
      phase retrieval method for coherent x-ray diffraction imaging (CXDI).
      Conventional phase retrieval methods effectively solve the problem for high
      signal-to-noise ratio measurements, but would not be sufficient for single
      biomolecular imaging which is expected to be realized with femto-second x-ray
      free electron laser pulses. The SPR method is based on the Bayesian statistics.
      It does not need to set the object boundary constraint that is required by the
      commonly used hybrid input-output (HIO) method, instead a prior distribution is
      defined with an exponential distribution and used for the estimation. Simulation
      results demonstrate that the proposed method reconstructs the electron density
      under a noisy condition even some central pixels are masked.

PMID- 22418097
TI  - Experimental multiplexing of encrypted movies using a JTC architecture.
AB  - We present the first experimental technique to encrypt a movie under a joint
      transform correlator architecture. We also extend the method to multiplex several
      movies in a single package. We use a Mach-Zehnder interferometer to encrypt
      experimentally each movie. One arm of the interferometer is the joint transform
      correlator and the other arm is the reference wave. We include the complete
      description of the procedure along with experimental results supporting the
      proposal.

PMID- 22418098
TI  - Passive Q-switching of the diode pumped Tm3+:KLu(WO4)2 laser near 2-MUm with
      Cr2+:ZnS saturable absorbers.
AB  - Single pulse energies as high as 145 uJ were generated with a passively Q
      switched diode-pumped Tm:KLu(WO<sub>4</sub>)<sub>2</sub> laser using poly
      crystalline Cr<sup>2+</sup>:ZnS as a saturable absorber. The maximum average
      power reached 0.39 W at a pulse repetition rate of 2.7 kHz with pulse durations
      in the 25 - 30 ns range. The maximum peak power amounted to 6 kW. The obtained
      results agree well with theoretical analysis.

PMID- 22418099
TI  - Modulation cancellation method for isotope 18O/16O ratio measurements in water.
AB  - The application of an innovative spectroscopic balancing technique to measure the
      isotope 18O/16O ratio in water vapor is reported. Quartz enhanced photoacoustic
      spectroscopy has been employed as the absorption sensing technique. Two isotope
      absorption lines with the same quantum numbers, with very close lower energy
      levels, have been selected to limit the sensitivity to temperature variations and
      guarantee identical broadening as well as relaxation properties. The sensitivity
      in measuring the deviation from a standard sample delta18O is 1.40/00, in 200 sec
      of integration time.

PMID- 22418100
TI  - Plasmon filters and resonators in metal-insulator-metal waveguides.
AB  - We present the numerical and experimental demonstration of plasmonic Bragg
      filters and resonators inside metal-insulator-metal (MIM) waveguides. The
      presented filters and resonators are fabricated using standard top down
      lithography methods. The optical bandgap of the integrated Bragg filters is
      experimentally observed and its optical properties are investigated as a function
      of the grating pitch and the number of grating periods. Transmission filters
      based on a nanocavity resonance were measured, obtaining Q-factors above 30.
      Tuning of the cavity wavelength was experimentally achieved by varying the cavity
      length.

PMID- 22418101
TI  - Optical features of a LiF crystal soft X-ray imaging detector irradiated by free
      electron laser pulses.
AB  - Optical features of point defects photoluminescence in LiF crystals, irradiated
      by soft X-ray pulses of the Free Electron Laser with wavelengths of 17.2 - 61.5
      nm, were measured. We found that peak of photoluminescence spectra lies near of
      530 nm and are associated with emission of F3+ centers. Our results suggest that
      redistribution of photoluminescence peak intensity from the red to the green part
      of the spectra is associated with a shortening of the applied laser pulses down
      to pico - or femtosecond durations. Dependence of peak intensity of
      photoluminescence spectra from the soft X-ray irradiation fluence was measured
      and the absence of quenching phenomena, even at relatively high fluencies was
      found, which is very important for wide applications of LiF crystal X-ray imaging
      detectors.

PMID- 22418102
TI  - High average-power ultrafast CPA Yb:KYW laser system with dual-slab amplifier.
AB  - A diode-pumped, ultrafast Yb:KYW laser system utilizing chirped-pulse
      amplification in a dual-slab regenerative amplifier with spectral shaping of
      seeding pulse from a master oscillator has been developed. A train of compressed
      pulses with pulse length of 181 fs, repetition rate up to 200 kHz, and average
      power exceeding 8 W after compression and pulse picker was achieved.

PMID- 22418103
TI  - Experimental and theoretical investigation of timing jitter inside a stretcher
      compressor setup.
AB  - In an optically synchronized short-pulse optical-parametric chirped-pulse
      amplification (OPCPA) system, we observe a few-100 fs-scale timing jitter. With
      an active timing stabilization system slow fluctuations are removed and the
      timing jitter can be reduced to 100 fs standard deviation (Std). As the main
      source for the timing fluctuations we could identify air turbulence in the
      stretcher-compressor setup inside the chirped pulse amplification (CPA) pump
      chain. This observation is supported by theoretical investigation of group delay
      changes for angular deviations occurring between the parallel gratings of a
      compressor or stretcher, as they can be introduced by air turbulence.

PMID- 22418104
TI  - Analysis of a distributed fiber-optic temperature sensor using single-photon
      detectors.
AB  - We demonstrate a high-accuracy distributed fiber-optic temperature sensor using
      superconducting nanowire single-photon detectors and single-photon counting
      techniques. Our demonstration uses inexpensive single-mode fiber at standard
      telecommunications wavelengths as the sensing fiber, which enables extremely low
      loss experiments and compatibility with existing fiber networks. We show that the
      uncertainty of the temperature measurement decreases with longer integration
      periods, but is ultimately limited by the calibration uncertainty. Temperature
      uncertainty on the order of 3 K is possible with spatial resolution of the order
      of 1 cm and integration period as small as 60 seconds. Also, we show that the
      measurement is subject to systematic uncertainties, such as polarization fading,
      which can be reduced with a polarization diversity receiver.

PMID- 22418105
TI  - Broadband dispersion compensation using inner cladding modes in photonic crystal
      fibers.
AB  - A photonic crystal fiber is optimized for chromatic dispersion compensation by
      using inner cladding modes. To this end, a photonic-oriented version of the
      downhill-simplex algorithm is employed. The numerical results show a dispersion
      profile that accurately compensates the targeted dispersion curve, as well as its
      dispersion slope. The presented fiber has a simple structure, while radiation
      losses can be reduced simply by adding a few more air-hole rings. Fabrication
      tolerances are also considered showing how fabrication inaccuracies effects can
      be overridden by just adjusting the compensation length.

PMID- 22418106
TI  - Impact of seed source power on dispersion-limited maximum reach in WDM-PONs using
      broadband light source seeded optical sources.
AB  - The maximum reach in a WDM-PON using a broadband light source (BLS) seeded
      optical source has been experimentally evaluated by taking into account both
      effects of dispersion-induced pulse broadening and excess intensity noise (EIN)
      increase. In order to investigate the impact of BLS seed source power on the
      dispersion-limited performance, the system's performance has been measured and
      compared as a function of the spectrum-sliced BLS seed power into a reflective
      semiconductor optical amplifier (RSOA). From the results, we confirmed that the
      maximum reach in a RSOA based WDM-PON was mainly degraded by the dispersion
      induced EIN increase. Therefore, by mitigating the effect of dispersion-induced
      EIN increase with a high seed power into a RSOA, the maximum reach in the WDM-PON
      using a BLS seeded RSOA source could be achieved to be ~60 km of single-mode
      fiber at the spectrum-sliced BLS seed power of >-10 dBm and a 1.25 Gb/s signal
      without using any dispersion-compensating techniques.

PMID- 22418107
TI  - Use of two-dimensional nanorod arrays with slanted ITO film to enhance optical
      absorption for photovoltaic applications.
AB  - Two-dimensional (2D) Si-nanorod arrays offer a promising architecture that has
      been widely recognized as attractive devices for photovoltaic applications. To
      further reduce the Fresnel reflection that occurs at the interface between the
      air and the 2D Si-nanorod array because of the large difference in their
      effective refractive indices, we propose and adopt a slanted ITO film as an
      intermediate layer by using oblique-angle sputtering deposition. The nearly
      continuous surface of the slanted ITO film is lossless and has high electrical
      conductivity; therefore, it could serve as an electrode layer for solar cells. As
      a result, the combination of the above-mentioned nanostructures exhibits high
      optical absorption over a broad range of wavelengths and incident angles, along
      with a calculated short-circuit current density of JSC = 32.81 mA/cm2 and a power
      generation efficiency of eta = 22.70%, which corresponds to an improvement of
      approximately 42% over that of its bare single-crystalline Si counterpart.

PMID- 22418108
TI  - Widely tunable femtosecond optical parametric oscillator based on silicon-on
      insulator waveguides.
AB  - A femtosecond optical parametric oscillator (OPO) based on silicon-on-insulator
      (SOI) waveguide is proposed and analyzed numerically. By utilizing split-step
      Fourier method (SSFM), it is demonstrated that ultra-wide tunable wavelength
      femtosecond pulse can be realized under the phase matching condition. Due to the
      interaction between nonlinearity and flexible dispersion design, the output
      signal wavelength can be tuned from 1645 to 1805 nm and the idler wavelength can
      be tuned from 1350 to 1456 nm. Moreover, the peak power of the output signal
      pulse exceeds 10 W from 1700 to 1770 nm with the pump peak power 50 W. The
      proposed OPO exhibits compact configuration and can find important applications
      in integrated broadband optical source.

PMID- 22418109
TI  - Photoinduced helical inversion in cholesteric liquid crystal cells with
      homeotropic anchoring.
AB  - Structural changes caused by the optically induced helical inversion in the
      cholesteric liquid crystal cells with homeotropic anchoring are studied. In a one
      step exposure, a sequence of structural transformations "lying left-handed helix 
      unwound homeotropic state - lying right-handed helix" is realized. In this
      process, smooth expansion of a left-handed helix, transition to an unwound state,
      emergence and smooth compression of a right-handed helix was observed. The
      unwound state was maintained over a rather wide range of exposures. Well-oriented
      and highly periodic fingerprint textures capable of the above mentioned
      structural changes were obtained by rubbing the aligning substrates. This allowed
      for obtaining photo-tunable diffraction gratings and using them to demonstrate
      new beam steering principle. Also, pitch reversal suggested new options for
      optical recording, in particular contrast reversal and edge enhancement.

PMID- 22418110
TI  - Control of spontaneous emission from a micro-wave driven atomic system.
AB  - We demonstrate coherent control of spontaneous emission from an indirectly
      coupled transition in a microwave driven four-level atomic system. The transition
      of concern is not directly coupled by any laser fields, while the ground state is
      coupled to another ground state by a microwave field. We show that the coupling
      of the microwave field produces interesting features such as double narrow lines
      in the emission spectrum. The heights, widths and positions of the emission peaks
      can be controlled by modifying the Rabi frequency and detuning of the microwave
      field. We discuss the spectra in the dressed states basis.

PMID- 22418111
TI  - Frozen and broadband slow light in coupled periodic nanowire waveguides.
AB  - We develop novel designs enabling slow-light propagation with vanishing group
      velocity dispersion ("frozen light") and slow-light with large delay-bandwidth
      product, in periodic nanowires. Our design is based on symmetry-breaking of
      periodic nanowire waveguides and we demonstrate its vailidy through two- and
      three-dimensional simulations. The slow-light is associated with a stationary
      inflection point which appears through coupling between forward and backward
      waveguide modes. The mode coupling also leads to evanescent modes, which enable
      efficient light coupling to the slow mode.

PMID- 22418112
TI  - Shading of a computer-generated hologram by zone plate modulation.
AB  - We propose a hologram calculation technique that enables reconstructing a shaded
      three-dimensional (3D) image. The amplitude distributions of zone plates, which
      generate the object points that constitute a 3D object, were two-dimensionally
      modulated. Two-dimensional (2D) amplitude modulation was determined on the basis
      of the Phong reflection model developed for computer graphics, which considers
      the specular, diffuse, and ambient reflection light components. The 2D amplitude
      modulation added variable and constant modulations: the former controlled the
      specular light component and the latter controlled the diffuse and ambient
      components. The proposed calculation technique was experimentally verified. The
      reconstructed image showed specular reflection that varied depending on the
      viewing position.

PMID- 22418113
TI  - First-order polarization mode dispersion compensator using two independent
      feedback signals enabling separation of principal states of polarization and
      differential group delay controls.
AB  - We propose and demonstrate a novel first-order polarization mode dispersion (PMD)
      compensator separating principal-states-of-polarization (PSP) control from
      differential-group-delay (DGD) control by using two independent feedback
      monitoring signals. To verify the proposed operating principle, we fabricated an
      automatically adaptive module-type 40-Gb/s PMD compensator on printed circuit
      boards. The results show that unlike previous typical compensation method of
      controlling alternately PSP and DGD, the proposed scheme provides independent
      continuous PSP tracking regardless of DGD control by delay line under rapidly
      varying PSP condition, thus resulting in stable compensated signal with reduction
      in compensation time.

PMID- 22418114
TI  - Optically-pumped dilute nitride spin-VCSEL.
AB  - We report the first room temperature optical spin-injection of a dilute nitride
      1300 nm vertical-cavity surface-emitting laser (VCSEL) under continuous-wave
      optical pumping. We also present a novel experimental protocol for the
      investigation of optical spin-injection with a fiber setup. The experimental
      results indicate that the VCSEL polarization can be controlled by the pump
      polarization, and the measured behavior is in excellent agreement with
      theoretical predictions using the spin flip model. The ability to control the
      polarization of a long-wavelength VCSEL at room temperature emitting at the
      wavelength of 1.3 um opens up a new exciting research avenue for novel uses in
      disparate fields of technology ranging from spintronics to optical
      telecommunication networks.

PMID- 22418115
TI  - Graphene-based polymer waveguide polarizer.
AB  - Planar-lightwave-circuit (PLC)-type graphene polarizers are fabricated by using a
      low loss optical polymer waveguide. The optical characteristics are investigated
      at a wavelength of 1.31 um. By interface engineering with a UV-curable
      perfluorinated acrylate polymer resin, the graphene's electrical properties are
      tuned to support a transverse-magnetic (TM) or transverse-electric (TE) surface
      wave. Thus, the fabricated PLC-type graphene polarizer serves alternatively as a
      TM-pass or TE-pass polarizer depending on the absence or presence of the upper
      cladding layer. The proposed planar-type graphene polarizer can be exploited
      further for on-chip photonic integrated circuit and devices.

PMID- 22418116
TI  - Orbital rotation without orbital angular momentum: mechanical action of the spin
      part of the internal energy flow in light beams.
AB  - The internal energy flow in a light beam can be divided into the "orbital" and
      "spin" parts, associated with the spatial and polarization degrees of freedom of
      light. In contrast to the orbital one, experimental observation of the spin flow
      seems problematic because it is converted into an orbital flow upon tight
      focusing of the beam, usually applied for energy flow detection by means of the
      mechanical action upon probe particles. We propose a two-beam interference
      technique that results in an appreciable level of spin flow in moderately focused
      beams and detection of the orbital motion of probe particles within a field where
      the transverse energy circulation is associated exclusively with the spin flow.
      This result can be treated as the first demonstration of mechanical action of the
      spin flow of a light field.

PMID- 22418117
TI  - Selecting detection wavelength of resonant cavity-enhanced photodetectors by
      guided-mode resonance reflectors.
AB  - We propose and demonstrate a novel device structure of resonant cavity-enhanced
      photodetector (RCE-PD). The new RCE-PD structure consists of a bottom distributed
      Bragg reflector (DBR), a cavity with InGaAs multiple quantum wells (MQWs) for
      light absorption and a top mirror of sub-wavelength grating. By changing the fill
      factor of the 2-D grating, the effective cavity length of RCE-PDs can be varied
      so the resonant wavelength can be selected post growth. Accordingly, we can
      fabricate an array of PDs on a single chip, on which every PD aims for a specific
      wavelength.

PMID- 22418118
TI  - A transmission-grating-modulated pump-probe absorption spectroscopy and
      demonstration of diffusion dynamics of photoexcited carriers in bulk intrinsic
      GaAs film.
AB  - A transmission-grating-modulated time-resolved pump-probe absorption spectroscopy
      is developed and formularized. The spectroscopy combines normal time-resolved
      pump-probe absorption spectroscopy with a binary transmission grating, is
      sensitive to the spatiotemporal evolution of photoinjected carriers, and has
      extensive applicability in the study of diffusion transport dynamics of
      photoinjected carriers. This spectroscopy has many advantages over reported
      optical methods to measure diffusion dynamics, such as simple experimental setup
      and operation, and high detection sensitivity. The measurement of diffusion
      dynamics is demonstrated on bulk intrinsic GaAs films. A carrier density
      dependence of carrier diffusion coefficient is obtained and agrees well with
      reported results.

PMID- 22418119
TI  - Suppression of extraneous thermal noise in cavity optomechanics.
AB  - Extraneous thermal motion can limit displacement sensitivity and radiation
      pressure effects, such as optical cooling, in a cavity-optomechanical system.
      Here we present an active noise suppression scheme and its experimental
      implementation. The main challenge is to selectively sense and suppress
      extraneous thermal noise without affecting motion of the oscillator. Our solution
      is to monitor two modes of the optical cavity, each with different sensitivity to
      the oscillator's motion but similar sensitivity to the extraneous thermal motion.
      This information is used to imprint "anti-noise" onto the frequency of the
      incident laser field. In our system, based on a nano-mechanical membrane coupled
      to a Fabry-Perot cavity, simulation and experiment demonstrate that extraneous
      thermal noise can be selectively suppressed and that the associated limit on
      optical cooling can be reduced.

PMID- 22418120
TI  - Two photon frequency conversion.
AB  - We study the case of two simultaneous three-wave-mixing processes, where one
      frequency is converted to another through an intermediate frequency. The common
      assumption is that these processes can occur only when the material is
      transparent at all participating frequencies. Here we show experimentally that,
      under appropriate conditions, the intermediate frequency remains dark throughout
      the interaction. This means that even if the material is opaque at the
      intermediate frequency, the conversion will remain efficient. New possibilities
      of frequency conversion are therefore available, e.g. through absorptive bands in
      the ultraviolet or mid-infrared. Moreover, though it was hitherto assumed that
      the phase mismatch value is governed only by dispersion, we show here that phase
      matching also depends on light intensity. These findings promise novel all
      optical switching techniques.

PMID- 22418121
TI  - Artificially disordered birefringent optical fibers.
AB  - We develop and experimentally verify a theory of evolution of polarization in
      artificially-disordered multi-mode optical fibers. Starting with a microscopic
      model of photo-induced index change, we obtain the first and second order
      statistics of the dielectric tensor in a Ge-doped fiber, where a volume disorder
      is intentionally inscribed via UV radiation transmitted through a diffuser. A
      hybrid coupled-power & coupled-mode theory is developed to describe the transient
      process of de-polarization of light launched into such a fiber. After certain
      characteristic distance, the power is predicted to be equally distributed over
      all co-propagating modes of the fiber regardless of their polarization.
      Polarization-resolved experiments, confirm the predicted evolution of the state
      of polarization. Complete mode mixing in a segment of fiber as short as ~ 10cm
      after 3.6dB insertion loss is experimentally observed. Equal excitation of all
      modes in such a multi-mode fiber creates the conditions to maximize the
      information capacity of the system under e.g. multiple-input-multiple-output
      (MIMO) transmission setup.

PMID- 22418122
TI  - Multi-beam bilateral teleoperation of holographic optical tweezers.
AB  - A multi-beam bilateral teleoperation system of holographic optical tweezers
      accelerated by a graphics processing unit is proposed and evaluated. This double
      arm teleoperation system is composed of two haptic devices and two laser-trapped
      micro-beads. Each micro-bead is trapped and moved following the trajectory of
      each haptic device, and the forces to which the micro-beads are subjected, which
      are generated by Stokes drag, are measured and fed back to an operator via the
      haptic devices. This real-time telexistence was quantitatively evaluated based on
      the time response of the trapped beads and the fed-back forces. And the
      demonstration of touching red blood cells shows the effectiveness of this system
      for biomedical application.

PMID- 22418123
TI  - Resolution limitations for tailored picture-generating freeform surfaces.
AB  - Picture-generating freeform surfaces are able to generate a picture in a defined
      plane by incoherent beam shaping comparable to illumination purposes. No
      classical imaging is performed. Therefore the classical Rayleigh criterion of the
      diffraction limit cannot be applied. In this paper, we investigate the physical
      light formation of picture-generating freeform surfaces using Fresnel-Huygens
      based simulations. A criterion for the diffraction limit was found. The
      resolution of such surfaces is significantly inferior to the resolution of
      classical imaging systems. However, in many cases, such systems are limited by
      the geometrical resolution. The influence of those two limitations were examined
      and a maximum of resolution, being limited by diffraction and by geometrical
      parameters can be found.

PMID- 22418124
TI  - Effects of laser polarization and interface orientation in harmonic generation
      microscopy.
AB  - We present systematic experimental investigations on the effects of laser
      polarization and interface orientation in second and third harmonic generation
      microscopy. We find that the laser polarization has no measurable effect on
      signal strength and resolution in third harmonic microscopy, while the second
      harmonic strongly depends upon the polarization direction of the driving laser.
      Moreover, we observe a strong effect of the interface orientation with respect to
      the laser beam direction-both in second and third harmonic generation. This
      affects the signal strength, as well as the obtained transversal and longitudinal
      resolution in microscopic imaging. As an (on the first glance) surprising
      feature, also surfaces parallel to the optical axis of the laser beam yield
      strong harmonic signal. This enables applications of harmonic microscopy in
      specific geometries. As an example we monitor the flow of immiscible microfluids
      in lateral cut by third harmonic microscopy.

PMID- 22418125
TI  - Polarizability of nanowires at surfaces: exact solution for general geometry.
AB  - The polarizability of a nanostructure is an important parameter that determines
      the optical properties. An exact semi-analytical solution of the electrostatic
      polarizability of a general geometry consisting of two segments forming a
      cylinder that can be arbitrarily buried in a substrate is derived using bipolar
      coordinates, cosine-, and sine-transformations. Based on the presented
      expressions, we analyze the polarizability of several metal nanowire geometries
      that are important within plasmonics. Our results provide physical insight into
      the interplay between the multiple resonances found in the polarizability of
      metal nanowires at surfaces.

PMID- 22418126
TI  - InAs/InP(100) quantum dot waveguide photodetectors for swept-source optical
      coherence tomography around 1.7 um.
AB  - In this paper a study of waveguide photodetectors based on InAs/InP(100) quantum
      dot (QD) active material are presented for the first time. These detectors are
      fabricated using the layer stack of semiconductor optical amplifiers (SOAs) and
      are compatible with the active-passive integration technology. We investigated
      dark current, responsivity as well as spectral response and bandwidth of the
      detectors. It is demonstrated that the devices meet the requirements for swept
      source optical coherent tomography (SS-OCT) around 1.7 MUm. A rate equation model
      for QD-SOAs was modified and applied to the results to understand the dynamics of
      the devices. The model showed a good match to the measurements in the 1.6 to 1.8
      MUm wavelength range by fitting only one of the carrier escape rates. An
      equivalent circuit model was used to determine the capacitances which dominated
      the electrical bandwidth.

PMID- 22418127
TI  - Giant resonance absorption in ultra-thin metamaterial periodic structures.
AB  - We study the interaction of an incident plane wave with a metamaterial periodic
      structure consisting of alternating layers of positive and negative refractive
      index with average zero refractive index. We show that the existence of very
      narrow resonance peaks for which giant absorption - 50% at layer thickness of 1%
      of the incident wavelength - is exhibited. Maximum absorption is obtained at a
      specific layer thickness satisfying the critical coupling condition. This
      phenomenon is explained by the Rayleigh anomaly and by the excitation of Fabry
      Perot modes in the periodic layer. In addition, we investigate the modes
      supported by the structures for several limiting cases, and show that zero phase
      accumulation in the periodic metamaterial is obtained at resonance.

PMID- 22418128
TI  - Polarization phase shifting dispersed fringe sensor.
AB  - The dispersed fringe sensor (DFS) has been demonstrated as an effective means of
      measuring mirror segment piston error for telescopes with primary mirror
      apertures below 10 meters. With larger proposed telescopes such as The Thirty
      Meter Telescope (TMT) and The European Large Telescope (ELT) including ever more
      segments, there is a need for improvement in the co-phasing capability for
      segmented primary mirrors. In this paper a novel DFS that employs polarization
      phase shifting technology is introduced. This novel technology provides system
      designers and engineers with a new tool to extend the dynamic range of a DFS.

PMID- 22418129
TI  - Combining red and blue-detuned optical potentials to form a Lamb-Dicke trap for a
      single neutral atom.
AB  - We propose and demonstrate a scheme for strong radial confinement of a single 87
      Rb atom by a bichromatic far-off resonance optical dipole trap (BFORT). The BFORT
      is composed of a blue-detuned Laguerre-Gaussian LG01 beam and a red-detuned
      Gaussian beam. The atomic oscillation frequency measurement shows that the
      effective trapping dimension is much sharper than that from a diffraction-limited
      microscopic objective. Theory shows that the added scattering rate due to
      imposing blue-detuned light is negligible when the temperature of the single
      atoms is close to ground state temperature. By carrying out sub-Doppler cooling,
      the mean energy of single atoms trapped in the BFORT is reduced to 15 +/- 1 MUK.
      The corresponding mean quantum number of radial vibration n is about 1.65, which
      satisfies the Lamb-Dicke regime. We conclude that the BFORT is a suitable Lamb
      Dicke trap for further cooling a single neutral atom down to the ground state and
      for further application in quantum information processing.

PMID- 22418130
TI  - Pulse compression of phase-matched high harmonic pulses from a time-delay
      compensated monochromator.
AB  - Single 32.6 eV high harmonic pulses from a time-delay compensated monochromator
      were compressed down to 11 +/- 3 fs by completely compensating for the pulse
      front tilt. The photon flux was intensified up to 5.7*10(9) photons/s on target
      by implementing high harmonic generation under a phase matching condition in a
      hollow fiber used for increasing the interaction length. The output photon flux
      on target from the monochromator was comparable to that from a small synchrotron
      facility, while the pulse duration was more than three orders of magnitude
      shorter. This high harmonic beam line fulfills two requirements for time-resolved
      spectroscopy in extreme ultraviolet region, namely, ultrashort pulses and high
      photon flux.

PMID- 22418132
TI  - Scattered light fluorescence microscopy in three dimensions.
AB  - Recently, we have proposed a method to image fluorescent structures behind turbid
      layers at diffraction limited resolution using wave-front shaping and the memory
      effect. However, this was limited to a raster scanning of the wave-front shaped
      focus to a two dimensional plane. In applications, it can however be of great
      importance to be able to scan a three dimensional volume. Here we show that this
      can be implemented in the same setup. This is achieved by the addition of a
      parabolic phase shift to the shaped wave-front. Via the memory effect, this phase
      shift leads to a shift of the interference based focus in the z-direction, thus
      opening the possibility of three dimensional imaging using scattered light
      fluorescence microscopy. Here, we show an example of such a three dimensional
      image of fluorescent nano-beads taken behind a turbid layer more than 10 mean
      free paths thick. Finally, we discuss the differences of the scanning in the z
      direction with that in the x-y plane and the corresponding possibilities and
      limitations of the technique.

PMID- 22418131
TI  - Enhanced photon absorption and carrier generation in nanowire solar cells.
AB  - Overall performance of a thin film solar cell is determined by the efficiency of
      converting photons to electrons through light absorption, carrier generation, and
      carrier collection. Recently, photon management has emerged as a powerful tool to
      further boost this conversion efficiency. Here we propose a novel nanograting
      solar cell design that achieves enhanced broadband light absorption and carrier
      generation in conjunction with the reduced use of active and non-earth-abundant
      materials. A test using this design for the short circuit current density in
      CuInxGa(1-x)Se2 (CIGS) thin film solar cells shows up to 250% enhancement when
      compared to the bare thin film cells. In addition, placing metal strips on top of
      the nanograting to act as the top electrode reduces the use of non-earth-abundant
      materials that is normally used as the transparent conducting materials. This
      novel solar cell design has the potential to become a new solar cell platform
      technology for various thin film solar cell systems.

PMID- 22418133
TI  - Quantifying the non-Gaussianity of the state of spatially correlated down
      converted photons.
AB  - The state of spatially correlated down-converted photons is usually treated as a
      two-mode Gaussian entangled state. While intuitively this seems to be reasonable,
      it is known that new structures in the spatial distributions of these photons can
      be observed when the phase-matching conditions are properly taken into account.
      Here, we study how the variances of the near- and far-field conditional
      probabilities are affected by the phase-matching functions, and we analyze the
      role of the EPR-criterion regarding the non-Gaussianity and entanglement
      detection of the spatial two-photon state of spontaneous parametric down
      conversion (SPDC). Then we introduce a statistical measure, based on the
      negentropy of the joint distributions at the near- and far-field planes, which
      allows for the quantification of the non-Gaussianity of this state. This measure
      of non-Gaussianity requires only the measurement of the diagonal covariance sub
      matrices, and will be relevant for new applications of the spatial correlation of
      SPDC in CV quantum information processing.

PMID- 22418134
TI  - Room-temperature continuous-wave operation of lateral current injection
      wavelength-scale embedded active-region photonic-crystal laser.
AB  - We have developed a wavelength-scale embedded active-region photonic-crystal
      laser using lateral p-i-n structure. Zn diffusion and Si ion implantation are
      used for p- and n-type doping. Room-temperature continuous-wave lasing behavior
      is clearly observed from the injection current dependence of the output power,
      3dB-bandwidth of the peak, and lasing wavelength. The threshold current is 390
      MUA and the estimated effective threshold current is 9.4 MUA. The output power in
      output waveguide is 1.82 MUW for a 2.0-mA current injection. These results
      indicate that the embedded active-region structure effectively reduce the thermal
      resistance. Ultrasmall electrically driven lasers are an important step towards
      on-chip photonic network applications.

PMID- 22418135
TI  - Network-embedded self-tuning cavity for WDM-PON transmitter.
AB  - A network-embedded self-tuning cavity is proved in wavelength division
      multiplexed passive optical network transmission over 32 channels. The external
      source-less topology takes advantage of a reflective element at the remote node
      and a reflective semiconductor optical amplifier at the optical network unit to
      establish a distribution-fiber based cavity. The bit error rate performance of up
      to 5-km cavities is presented with two optical network units simultaneously
      operating and with downstream signal co presence. The experimental analysis at
      1.25 Gb/s provides an evaluation of polarization dependences when exploiting low
      polarization dependent gain reflective semiconductor optical amplifiers with 25
      km and 50-km standard single mode fiber transmission.

PMID- 22418136
TI  - Calibration of the optical torque wrench.
AB  - The optical torque wrench is a laser trapping technique that expands the
      capability of standard optical tweezers to torque manipulation and measurement,
      using the laser linear polarization to orient tailored microscopic birefringent
      particles. The ability to measure torque of the order of kBT (~4 pN nm) is
      especially important in the study of biophysical systems at the molecular and
      cellular level. Quantitative torque measurements rely on an accurate calibration
      of the instrument. Here we describe and implement a set of calibration approaches
      for the optical torque wrench, including methods that have direct analogs in
      linear optical tweezers as well as introducing others that are specifically
      developed for the angular variables. We compare the different methods, analyze
      their differences, and make recommendations regarding their implementations.

PMID- 22418137
TI  - Superbroadband near-IR photoluminescence from Pr3+-doped fluorotellurite glasses.
AB  - Praseodymium(Pr3+)-doped fluorotellurite glasses were synthesized and broadband
      photoluminescence (PL) covering a wavelength range from 1.30 to 1.67 MUm was
      observed under both 488 and 590 nm wavelength excitations. The broadband PL
      emission is mainly due to the radiative transition from the manifolds Pr3+: 1D2
      to 1G4. The PL line-shape, band width, and lifetime were modified by the Pr3+
      dopant concentration, and a quantum efficiency as high as 73.7% was achieved with
      Pr3+ dopant in a low concentration of 0.05 mol%. The good spectroscopic
      properties were also predicted by the Judd-Ofelt analysis, which indicates a
      stronger asymmetry and covalent bonding between the Pr3+ sites and the matrix
      lifgand field. The large stimulated emission cross-section, long measured
      lifetime, and broad emission bandwidth confirm the potential of the Pr3+-singly
      doped fluorotellurite glass as broadband luminescence sources for the broadband
      near-infrared optical amplifications and tunable lasers.

PMID- 22418138
TI  - Mid- to long-wavelength infrared plasmonic-photonics using heavily doped n-Ge/Ge
      and n-GeSn/GeSn heterostructures.
AB  - Heavily doped n-type Ge and GeSn are investigated as plasmonic conductors for
      integration with undoped dielectrics of Si, SiGe, Ge, and GeSn in order to create
      a foundry-based group IV plasmonics technology. N-type Ge1-xSnx with compositions
      of 0 <= x <= 0.115 are investigated utilizing effective-mass theory and Drude
      considerations. The plasma wavelengths, relaxation times, and complex
      permittivities are determined as functions of the free carrier concentration over
      the range of 10(10) to 10(21) cm-3. Basic plasmonic properties such as
      propagation loss and mode height are calculated and example numerical simulations
      are shown of a dielectric-conductor-dielectric ribbon waveguide structure are
      shown. Practical operation in the 2 to 20 MUm wavelength range is predicted.

PMID- 22418139
TI  - Fabrication and experimental demonstration of the first 160 Gb/s hybrid silicon
      on-insulator integrated all-optical wavelength converter.
AB  - We present a hybrid integrated photonic circuit on a silicon-on-insulator
      substrate that performs ultra high-speed all-optical wavelength conversion. The
      chip incorporates a 1.25 mm non-linear SOA mounted on the SOI board using gold
      tin bumps as small as 14 MUm. Tauhe device performs chirp filtering and signal
      polarity inversion with two multi-mode interference (MMI) - based cascaded delay
      interferometers (DIs) monolithically integrated on the same SOI substrate. Full
      free spectral range (FSR) tuning of the DIs is accomplished by two independently
      tuneable on-chip thermal heaters. We demonstrate 160Gb/s all-optical wavelength
      conversion with power penalties of less than 4.6dB.

PMID- 22418140
TI  - Low loss depressed cladding waveguide inscribed in YAG:Nd single crystal by
      femtosecond laser pulses.
AB  - A depressed cladding waveguide with record low loss of 0.12 dB/cm is inscribed in
      YAG:Nd(0.3at.%) crystal by femtosecond laser pulses with an elliptical beam
      waist. The waveguide is formed by a set of parallel tracks which constitute the
      depressed cladding. It is a key element for compact and efficient CW waveguide
      laser operating at 1064 nm and pumped by a multimode laser diode. Special
      attention is paid to mechanical stress resulting from the inscription process.
      Numerical calculation of mode distribution and propagation loss with the elasto
      optical effect taken into account leads to the conclusion that the depressed
      cladding is a dominating factor in waveguide mode formation, while the mechanical
      stress only slightly distorts waveguide modes.

PMID- 22418141
TI  - Pulse duration and energy scaling of femtosecond all-normal dispersion fiber
      oscillators.
AB  - We investigate the scaling properties of mode-locked all-normal dispersion fiber
      oscillators in terms of output pulse energy and compressed pulse duration.
      Experimental results are achieved by stepwise variation of the resonator
      dispersion, total fiber length, and the spectral filter bandwidth. Adjustment of
      these parameters enables pulse duration scaling down to 31 fs and increase of
      output pulse energy up to 84 nJ.

PMID- 22418142
TI  - Optical color-image encryption and synthesis using coherent diffractive imaging
      in the Fresnel domain.
AB  - We propose a new method using coherent diffractive imaging for optical color
      image encryption and synthesis in the Fresnel domain. An optical multiple-random
      phase-mask encryption system is applied, and a strategy based on lateral
      translations of a phase-only mask is employed during image encryption. For the
      decryption, an iterative phase retrieval algorithm is applied to extract high
      quality decrypted color images from diffraction intensity maps (i.e.,
      ciphertexts). In addition, optical color-image synthesis is also investigated
      based on coherent diffractive imaging. Numerical results are presented to
      demonstrate feasibility and effectiveness of the proposed method. Compared with
      conventional interference methods, coherent diffractive imaging approach may open
      up a new research perspective or can provide an effective alternative for optical
      color-image encryption and synthesis.

PMID- 22418143
TI  - Terahertz quantum cascade lasers operating up to ~ 200 K with optimized
      oscillator strength and improved injection tunneling.
AB  - A new temperature performance record of 199.5 K for terahertz quantum cascade
      lasers is achieved by optimizing the lasing transition oscillator strength of the
      resonant phonon based three-well design. The optimum oscillator strength of 0.58
      was found to be larger than that of the previous record (0.41) by Kumar et al.
      [Appl. Phys. Lett. 94, 131105 (2009)]. The choice of tunneling barrier
      thicknesses was determined with a simplified density matrix model, which
      converged towards higher tunneling coupling strengths than previously explored
      and nearly perfect alignment of the states across the injection and extraction
      barriers at the design electric field. At 8 K, the device showed a threshold
      current density of 1 kA/cm2, with a peak output power of ~ 38 mW, and lasing
      frequency blue-shifting from 2.6 THz to 2.85 THz with increasing bias. The
      wavelength blue-shifted to 3.22 THz closer to the maximum operating temperature
      of 199.5 K, which corresponds to ~ 1.28homega/kappaB. The voltage dependence of
      laser frequency is related to the Stark effect of two intersubband transitions
      and is compared with the simulated gain spectra obtained by a Monte Carlo
      approach.

PMID- 22418144
TI  - Performance comparison of MSK and QPSK optical long haul DWDM transmission with
      coherent detection.
AB  - We performed long-haul WDM transmission experiments to compare 10 Gbit/s MSK and
      QPSK modulation with a channel grid of 12.5 GHz. A standard link setup with
      inline dispersion compensation was applied in combination with coherent detection
      and following offline signal processing. Both modulation formats showed nearly
      equal performance bridging about 4000 km at a BER of 10(-3).

PMID- 22418145
TI  - Advanced broadband monitoring for thin film deposition through equivalent optical
      admittance loci observation.
AB  - A monitoring technique using the equivalent optical admittance loci of thin films
      to control the deposition is presented. Real-time broadband spectrum measurements
      are employed to extract the real-time thin film refraction index and thickness,
      and the corresponding equivalent optical admittance is thereby obtained. This
      monitoring method can predict the termination point of the deposition process and
      avoid the termination ambiguities, which generally appear with other broadband
      monitors. Compared to other monitoring methods, the experimental results of the
      proposed monitoring technique show better error compensation ability.

PMID- 22418146
TI  - Single mode quantum cascade lasers with shallow-etched distributed Bragg
      reflector.
AB  - We report the fabrication of single mode quantum cascade lasers using a shallow
      etched distributed Bragg reflector as frequency selective element. Quasi
      continuous single mode tuning over 15 cm-1 at room temperature and 25 cm-1 via
      temperature tuning at Peltier temperatures is demonstrated. The behavior of both
      electro-optic and spectral characteristics under variation of the segment
      currents is analyzed, showing a maximum peak output power at room temperature of
      600 mW. Thermal crosstalk between the laser segments is investigated. The
      spectral resolution of a gas absorption experiment is determined to be better
      than 0.0078 cm-1.

PMID- 22418147
TI  - Dirac cone in two- and three-dimensional metamaterials.
AB  - It is shown by analytical calculation based on the tight-binding approximation
      that the isotropic Dirac cone in the Brillouin zone center can be created in two-
      and three-dimensional periodic metamaterials by accidental degeneracy of two
      modes. In the case of two dimensions, the combination of a doubly degenerate E
      mode and a non-degenerate A1 mode of the square lattice of the C4v symmetry is
      examined. For three dimensions, the combination of a triply degenerate T1u mode
      and a non-degenerate A1g mode of the cubic lattice of the Oh symmetry is
      examined. The secular equation of the electromagnetic field is derived and solved
      with detailed analysis of electromagnetic transfer integrals by group theory.
      This is the first theoretical prediction of the presence of the Dirac cone in the
      three-dimensional periodic structure.

PMID- 22418148
TI  - Accommodation measurements of horizontally scanning holographic display.
AB  - Eye accommodation is considered to function properly for three-dimensional (3D)
      images generated by holography. We developed a horizontally scanning holographic
      display technique that enlarges both the screen size and viewing zone angle. A 3D
      image generated by this technique can be easily seen by both eyes. In this study,
      we measured the accommodation responses to a 3D image generated by the
      horizontally scanning holographic display technique that has a horizontal viewing
      zone angle of 14.6 degrees  and screen size of 4.3 in. We found that the
      accommodation responses to a 3D image displayed within 400 mm from the display
      screen were similar to those of a real object.

PMID- 22418149
TI  - Influence of excitation power and temperature on photoluminescence in InGaN/GaN
      multiple quantum wells.
AB  - Excitation power and temperature dependences of the photoluminescence (PL)
      spectra are studied in InGaN/GaN multiple quantum wells (MQWs). The excitation
      power dependences of the PL peak energy and linewidth indicate that the emission
      process of the MQWs is dominated first by the Coulomb screening effect and then
      by the localized states filling at low temperature, and that the nonradiative
      centers are thermally activated in low excitation range at room temperature. The
      anomalous temperature dependences of the peak energy and linewidth are well
      explained by the localized carrier hopping and thermalization process, and by the
      exponentially increased density of states with energy in the band tail. Moreover,
      it is also found that internal quantum efficiency is related to the mechanism
      conversion from nonradiative to radiative mechanism, and up to the carriers
      escaping from localized states.

PMID- 22418150
TI  - Low threshold current and widely tunable external cavity lasers with chirped
      multilayer InAs/InGaAs/GaAs quantum-dot structure.
AB  - Low threshold and widely tunable InAs/GaAs quantum-dot lasers are implemented
      with grating-coupled external-cavity arrangement. Throughout the tuning range of
      130 nm, from 1160 to 1290 nm, the threshold current density is not more than 0.9
      kA/cm2 and no noticeable threshold jump is observed. For a shorter-cavity device,
      the injection current is kept at a record low value of 90 mA but the tuning range
      is further extended to 150 nm, from 1143 to 1293 nm. The effect of cavity length
      on the tuning characteristics is discussed and the strategy for design and
      optimization of multilayer quantum-dot structure is also proposed.

PMID- 22418151
TI  - Multi-directional Cerenkov second harmonic generation in two-dimensional
      nonlinear photonic crystal.
AB  - We study Cerenkov-type second-harmonic generation in a two-dimensional quasi
      periodically poled LiNbO3 crystal. We employ a new geometry of interaction to
      observe simultaneous emission of multi-directional nonlinear Cerenkov radiation
      with comparable intensities. This opens a way to control the angle of Cerenkov
      emission by tailoring the nonlinearity of the material, which is otherwise
      intrinsically defined by dielectric constants of the medium and their dispersion.

PMID- 22418152
TI  - Precise and rapid distance measurements by scatterometry.
AB  - We found that the distances between isolated scatterers with similar columnar
      shapes could be measured by taking a single Fourier transform of their
      diffraction intensity. If the scatterers have different shapes, the distances
      between similar shapes can be selected from the distances between all the shapes.
      The distance from a specific scatterer can be measured with a resolution of 0.8
      wavelengths and a precision of 0.01 wavelengths. This technique has the potential
      to be used in a novel optical memory that has a memory density as high as that of
      holographic memory, while can be fabricated by simple transfer molding. We used
      rigorous coupled-wave analysis to calculate the diffraction intensity. Some of
      the results were verified by nonstandard finite-difference time-domain
      simulations and experiments.

PMID- 22418153
TI  - Spatial coherence of electron bunches extracted from an arbitrarily shaped cold
      atom electron source.
AB  - We describe the spatial coherence properties of a cold atom electron source in
      the framework of a quasihomogeneous wavefield. The model is used as the basis for
      direct measurements of the transverse spatial coherence length of electron
      bunches extracted from a cold atom electron source. The coherence length is
      determined from the measured visibility of a propagated electron distribution
      with a sinusoidal profile of variable spatial frequency. The electron
      distribution was controlled via the intensity profile of an atomic excitation
      laser beam patterned with a spatial light modulator. We measure a lower limit to
      the coherence length at the source of lc = 7.8 +/- 0.9 nm.

PMID- 22418154
TI  - Framework for computing the spatial coherence effects of polycapillary x-ray
      optics.
AB  - Despite the extensive use of polycapillary x-ray optics for focusing and
      collimating applications, there remains a significant need for characterization
      of the coherence properties of the output wavefield. In this work, we present the
      first quantitative computational method for calculation of the spatial coherence
      effects of polycapillary x-ray optical devices. This method employs the coherent
      mode decomposition of an extended x-ray source, geometric optical propagation of
      individual wavefield modes through a polycapillary device, output wavefield
      calculation by ray data resampling onto a uniform grid, and the calculation of
      spatial coherence properties by way of the spectral degree of coherence.

PMID- 22418155
TI  - Room-temperature operation of npn- AlGaInAs/InP multiple quantum well transistor
      laser emitting at 1.3-um wavelength.
AB  - Room-temperature pulsed operation of a 1.3-um wavelength transistor laser (TL),
      consisting of a buried heterostructure (BH) with an npn configuration and an
      AlGaInAs/InP multiple-quantum-well (MQW) active region, was successfully
      attained. A threshold base current of 18 mA (threshold emitter current of 150 mA)
      was obtained with a stripe width of 1.3 um and a cavity length of 500 um. The
      transistor activity as well as the lasing operation were achieved at the same
      time, which is essential for the high-speed operation of TLs.

PMID- 22418156
TI  - Nonlinear microscopy techniques for assessing the UV laser polymer interactions.
AB  - A new diagnostic approach for assessing the in-depth laser induced modifications
      upon ultraviolet polymer irradiation is presented. The methodology relies on the
      observation of morphological alterations in the bulk material (Paraloid B72) by
      using third harmonic generation. This non destructive methodology allows the
      detailed and accurate imaging of the structurally laser modified zone extent in
      the vicinity of the irradiated area. Additionally, for the first time, the
      visualization and quantitative determination of the contour of the laser-induced
      swelling/bulk material interface is reported. The observed polymer surface
      swelling following single-pulse KrF laser irradiation at sub-ablation fluences is
      interpreted in the context of a model for laser-induced bubble formation due to
      droplet explosion mechanism.

PMID- 22418157
TI  - Thermally induced waveguide changes in active fibers.
AB  - Thermally induced waveguide changes become significant for very large mode area
      fibers. This results in a reduction of the mode-field diameter, but
      simultaneously in an improvement of the beam quality. In this work the first
      systematic experimental characterization of the reduction of the mode-field
      diameter in various fibers during high-power operation is carried out. It is
      shown that the reduction of the mode-field diameter shows a characteristic
      behavior that scales with the core size but that is independent of the particular
      fiber design. Furthermore, the strength of the actual index change is
      experimentally estimated, and its use to overcome avoided crossings is discussed
      and experimentally demonstrated.

PMID- 22418158
TI  - Analytic models of spectral responses of fiber-grating-based interferometers on
      FMC theory.
AB  - In this paper the analytic models (AMs) of the spectral responses of fiber
      grating-based interferometers are derived from the Fourier mode coupling (FMC)
      theory proposed recently. The interferometers include Fabry-Perot cavity, Mach
      Zehnder and Michelson interferometers, which are constructed by uniform fiber
      Bragg gratings and long-period fiber gratings, and also by Gaussian-apodized
      ones. The calculated spectra based on the analytic models are achieved, and
      compared with the measured cases and those on the transfer matrix (TM) method.
      The calculations and comparisons have confirmed that the AM-based spectrum is in
      excellent agreement with the TM-based one and the measured case, of which the
      efficiency is improved up to ~2990 times that of the TM method for non-uniform
      grating-based in-fiber interferometers.

PMID- 22418159
TI  - Generation of real-time large computer generated hologram using wavefront
      recording method.
AB  - We report the generation of a real-time large computer generated hologram (CGH)
      using the wavefront recording plane (WRP) method with the aid of a graphics
      processing unit (GPU). The WRP method consists of two steps: the first step
      calculates a complex amplitude on a WRP that is placed between a 3D object and a
      CGH, from a three-dimensional (3D) object. The second step obtains a CGH by
      calculating diffraction from the WRP to the CGH. The disadvantages of the
      previous WRP method include the inability to record a large three-dimensional
      object that exceeds the size of the CGH, and the difficulty in implementing to
      all the steps on a GPU. We improved the WRP method using Shifted-Fresnel
      diffraction to solve the former problem, and all the steps could be implemented
      on a GPU. We show optical reconstructions from a 1,980 * 1,080 phase only CGH
      generated by about 3 * 10(4) object points over 90 frames per second. In other
      words, the improved method obtained a large CGH with about 6 mega pixels (1,980 *
      1,080 * 3) from the object points at the video rate.

PMID- 22418160
TI  - Single-layer resonant-waveguide grating for polarization and wavelength selection
      in Yb:YAG thin-disk lasers.
AB  - A single-layer resonant-waveguide grating consisting of a sub-wavelength grating
      coupler etched into a waveguide is proposed in order to achieve high polarization
      and high spectral selectivity inside an Yb:YAG thin-disk laser resonator. The
      designed structure was fabricated with the help of a Lloyd's-mirror interference
      lithography setup followed by reactive ion beam etching down to the desired
      grating groove depth. The wavelength and polarization dependent reflectivity is
      measured and compared to the design results. The behaviour of the device at
      higher temperatures is also investigated in the present work. The device is
      introduced as the end mirror of an Yb:YAG thin-disk laser cavity. Output powers
      of up to 123 W with a spectral bandwidth of about 0.5 nm (FWHM) is demonstrated
      in a multimode configuration (M2~6). In fundamental-mode operation (TEM00 with
      M2~1.1) 70 W of power with a spectral bandwidth of about 20 pm have been
      obtained. Moreover, the degree of linear polarization was measured to be higher
      than 99% for both multimode and fundamental mode operation.

PMID- 22418161
TI  - Compact electric field sensors based on indirect bonding of lithium niobate to
      silicon microrings.
AB  - An electric field sensor based on the indirect bonding of submicrometer thin
      films of lithium niobate to silicon microring resonators is presented using
      benzocyclobutene as an intermediate bonding layer. The hybrid material system
      combines the electro-optic functionality of lithium niobate with the high-index
      contrast of silicon waveguides, enabling compact and metal-free electric field
      sensors. A sensor is designed and fabricated using ion-sliced z-cut lithium
      niobate as the top cladding of a 20 MUm radius silicon microring resonator. The
      optical quasi transverse magnetic mode is used to access the largest electro
      optic coefficient in the lithium niobate. Optical characterization of the hybrid
      device results in a measured loaded quality factor of 13,000 in the infrared.
      Operation of the device as an electric field sensor is demonstrated by detecting
      the fringing fields from a microstrip electrical circuit operating at 1.86 GHz.
      The demonstrated sensitivity to electric fields is 4.5 V m-1 Hz-1/2.

PMID- 22418162
TI  - Three-dimensional structure of a single colloidal crystal grain studied by
      coherent x-ray diffraction.
AB  - A coherent x-ray diffraction experiment was performed on an isolated colloidal
      crystal grain at the coherence beamline P10 at PETRA III. Using azimuthal
      rotation scans the three-dimensional (3D) scattered intensity from the sample in
      the far-field was measured. It includes several Bragg peaks as well as the
      coherent interference around these peaks. The analysis of the scattered intensity
      reveals the presence of plane defects in a single grain of the colloidal sample.
      We confirm these findings by model simulations. In these simulations we also
      analyze the experimental conditions required to phase the 3D diffraction pattern
      from a single colloidal grain. This approach has the potential to produce a high
      resolution image of the sample revealing its inner structure, with possible
      structural defects.

PMID- 22418163
TI  - Observations on the linear programming formulation of the single reflector design
      problem.
AB  - We implemented the linear programming approach proposed by Oliker and by Wang to
      solve the single reflector problem for a point source and a far-field target. The
      algorithm was shown to produce solutions that aim the input rays at the
      intersections between neighboring reflectors. This feature makes it possible to
      obtain the same reflector with a low number of rays - of the order of the number
      of targets - as with a high number of rays, greatly reducing the computation
      complexity of the problem.

PMID- 22418164
TI  - Enhanced transmittance and hydrophilicity of nanostructured glass substrates with
      antireflective properties using disordered gold nanopatterns.
AB  - We fabricated surface nanostructures with different pillar and cone shapes on
      glass substrates using thermally dewetted gold (Au) nanoparticles as etch masks
      by dry etching. Their optical total transmittance characteristics, together with
      theoretical predictions using rigorous coupled-wave analysis simulation, and
      wetting behaviors were investigated. The nanostructured glass substrates strongly
      enhanced the surface transmission compared to the flat glass substrate. The glass
      nanocones with a linearly graded effective refractive index profile exhibited
      better transmission properties than the glass nanopillars due to the lower
      surface reflectance, thus leading to higher average transmittance with increasing
      their height. For the glass nanocones with a period of 106 +/- 39 nm at the Au
      film thickness of 5 nm, the higher average total transmittance (Tave) and solar
      weighted transmittance (SWT) of ~95.5 and ~95.8% at wavelengths of 300-1100 nm
      and the lower contact angle (thetac) of 31 degrees  were obtained compared to the
      flat glass substrate (i.e., Tave~92.7%, SWT~92.7%, and thetac~65 degrees ). The
      calculated total transmittance results showed a similar tendency to the
      experimental results.

PMID- 22418165
TI  - Surface plasmon-enhanced terahertz emission from a hemicyanine self-assembled
      monolayer.
AB  - Emission of terahertz radiation is observed when surface plasmons are excited on
      a thin film of gold, in the Kretschmann geometry. When a hemicyanine-terminated
      alkanethiol self-assembled monolayer of thickness 1.2 nm is deposited on the gold
      film, stronger terahertz emission is observed. Our experimental results confirm
      that enhanced terahertz emission is possible from planar gold surfaces when
      surface plasmons are excited.

PMID- 22418166
TI  - Complete measurement of fiber modal content by wavefront analysis.
AB  - We propose and demonstrate the use of a wavefront analyzer based on lateral
      shearing interferometry to characterize the modal content of multimode fibers.
      This wavefront measurement technique is applied to large mode area fibers, and
      allows us to recover both the intensity and relative phase of each guided mode.
      This constitutes an innovative complete characterization of the beam, and might
      be used as a probe in deterministic active wavefront correction techniques.

PMID- 22418167
TI  - Ultrafast nonlinear optical studies of silicon nanowaveguides.
AB  - Results of a self-consistent ultrafast study of nonlinear optical properties of
      silicon nanowaveguides using heterodyne pump-probe technique are reported. The
      two-photon absorption coefficient and free-carrier absorption effective cross
      section were determined to be 0.68cm/GW, and 1.9x10(-17) cm2, respectively and
      the Kerr coefficient and free-carrier-induced refractive index change 0.32x10(
      13) cm2/W, and -5.5x10(-21) cm3, respectively. The effects of the proton
      bombardment on the linear loss and the carrier lifetime of the devices were also
      studied. Carrier lifetime reduction from 330ps to 33ps with a linear loss of only
      14.8dB/cm was achieved using a proton bombardment level of 10(15)/cm2.

PMID- 22418168
TI  - 10 GHz femtosecond pulse interleaver in planar waveguide technology.
AB  - Coherent pulse interleaving implemented in planar waveguide technology is
      presented as a compact and robust solution to generate high repetition rate
      frequency combs. We demonstrate a 10 GHz pulse train from an Er-doped femtosecond
      fiber laser that is coupled into waveguide interleavers and multiplied in
      repetition rate by a factor of 16. With thermal tuning of the chip elements, we
      achieve optical and RF sidemode suppression levels of at least -30 dB.

PMID- 22418169
TI  - D-Scan measurement of ablation threshold incubation effects for ultrashort laser
      pulses.
AB  - We report the validation of the Diagonal Scan (D-Scan) technique to determine the
      incubation parameter for ultrashort laser pulses ablation. A theory to calculate
      the laser pulses superposition and a procedure for quantifying incubation effects
      are described, and the results obtained for BK7 samples in the 100 fs regime are
      compared to the ones given by the traditional method, showing a good agreement.

PMID- 22418170
TI  - Near-field probing of slow Bloch modes on photonic crystals with a nanoantenna.
AB  - We study the near-field probing of the slow Bloch laser mode of a photonic
      crystal by a bowtie nano-aperture (BNA) positioned at the end of a metal-coated
      fiber probe. We show that the BNA acts as a polarizing nanoprobe allowing us to
      extract information about the polarization of the near-field of the slow-light
      mode, without causing any significant perturbation of the lasing process. Near
      field experiments reveal a spatial resolution better than lambda/20 and a
      polarization ratio as strong as 110. We also demonstrate that the collection
      efficiency is two orders of magnitude larger for the BNA than for a 200 nm large
      circular aperture opened at the apex of the same metal-coated fiber tip. The BNA
      allows for overcoming one of the main limitations of SNOM linked to the well
      known trade off between resolution and signal-to-noise ratio.

PMID- 22418171
TI  - VECSEL gain characterization.
AB  - We present the first full gain characterization of two vertical external cavity
      surface emitting laser (VECSEL) gain chips with similar designs operating in the
      960-nm wavelength regime. We optically pump the structures with continuous-wave
      (cw) 808-nm radiation and measure the nonlinear reflectivity for 130-fs and 1.4
      ps probe pulses as function of probe pulse fluence, pump power, and heat sink
      temperature. With this technique we are able to measure the saturation behavior
      for VECSEL gain chips for the first time. The characterization with 1.4-ps pulses
      resulted in saturation fluences of 40-80 MUJ/cm2, while probing with 130-fs
      pulses yields reduced saturation fluences of 30-50 MUJ/cm2 for both structures.
      For both pulse durations this is lower than previously assumed. A small-signal
      gain of up to 5% is obtained with this technique. Furthermore, in a second
      measurement setup, we characterize the spectral dependence of the gain using a
      tunable cw probe beam. We measure a gain bandwidth of over 26 nm for both
      structures, full width at half maximum.

PMID- 22418172
TI  - Femtosecond free-electron laser x-ray diffraction data sets for algorithm
      development.
AB  - We describe femtosecond X-ray diffraction data sets of viruses and nanoparticles
      collected at the Linac Coherent Light Source. The data establish the first large
      benchmark data sets for coherent diffraction methods freely available to the
      public, to bolster the development of algorithms that are essential for
      developing this novel approach as a useful imaging technique. Applications are 2D
      reconstructions, orientation classification and finally 3D imaging by assembling
      2D patterns into a 3D diffraction volume.

PMID- 22418173
TI  - Optoacoustic monitoring of cerebral venous blood oxygenation though intact scalp
      in large animals.
AB  - Monitoring (currently invasive) of cerebral venous blood oxygenation is a key to
      avoiding hypoxia-induced brain injury resulting in death or severe disability.
      Noninvasive, optoacoustic monitoring of cerebral venous blood oxygenation can
      potentially replace existing invasive methods. To the best of our knowledge, we
      report for the first time noninvasive monitoring of cerebral venous blood
      oxygenation through intact scalp that was validated with invasive, "gold
      standard" measurements. We performed an in vivo study in the sheep superior
      sagittal sinus (SSS), a large midline cerebral vein, using our novel, multi
      wavelength optoacoustic system. The study results demonstrated that: 1) the
      optoacoustic signal from the sheep SSS is detectable through the thick, intact
      scalp and skull; 2) the SSS signal amplitude correlated well with wavelength and
      actual SSS blood oxygenation measured invasively using SSS catheterization, blood
      sampling, and measurement with "gold standard" CO-Oximeter; 3) the
      optoacoustically predicted oxygenation strongly correlated with that measured
      with the CO-Oximeter. Our results indicate that monitoring of cerebral venous
      blood oxygenation may be performed in humans noninvasively and accurately through
      the intact scalp using optoacoustic systems because the sheep scalp and skull
      thickness is comparable to that of humans whereas the sheep SSS is much smaller
      than that of humans.

PMID- 22418174
TI  - Array of tapered semiconductor waveguides in a fiber for infrared image transfer
      and magnification.
AB  - The proof-of-concept of an infrared imaging tip by an array of infrared
      waveguides tapered as small as 2 MUm is demonstrated. The fabrication is based on
      a high-pressure chemical fluid deposition technique to deposit precisely defined
      periodic arrays of Ge and Si waveguides within a microstructured optical fiber
      template made of silica to demonstrate the proposed concept at wavelengths of
      10.64 um and 1.55 um, respectively. The essential features of the imaging system
      such as isolation between adjacent pixels, magnification, optical throughput, and
      image transfer characteristics are investigated. Near-field scanning at 3.39 MUm
      wavelength using a single tapered Ge core is also demonstrated.

PMID- 22418175
TI  - Modified field enhancement and extinction by plasmonic nanowire dimers due to
      nonlocal response.
AB  - We study the effect of nonlocal optical response on the optical properties of
      metallic nanowires, by numerically implementing the hydrodynamical Drude model
      for arbitrary nanowire geometries. We first demonstrate the accuracy of our
      frequency-domain finite-element implementation by benchmarking it in a wide
      frequency range against analytical results for the extinction cross section of a
      cylindrical plasmonic nanowire. Our main results concern more complex geometries,
      namely cylindrical and bow-tie nanowire dimers that can strongly enhance optical
      fields. For both types of dimers we find that nonlocal response can strongly
      affect both the field enhancement in between the dimers and their respective
      extinction cross sections. In particular, we give examples of blueshifted maximal
      field enhancements near hybridized plasmonic dimer resonances that are still
      large but nearly two times smaller than in the usual local-response description.
      For the same geometry at a fixed frequency, the field enhancement and cross
      section can also be significantly more enhanced in the nonlocal-response model.

PMID- 22418176
TI  - Electrical tracing-assisted dual-microring label-free optical bio/chemical
      sensors.
AB  - We propose and demonstrate a novel electrical tracing-assisted dual-microring
      resonator-based optical sensor system in silicon-on-insulator substrate. The
      system comprises one microring resonator-based sensing element and another
      microring resonator-based tracing element integrated with electrical controller.
      The resonance wavelength shift of sensing microring induced by the refractive
      index change is traced and determined by direct voltage supply of the electrical
      tunable tracing microring. Such optical sensing system eliminates the traditional
      wavelength-scanning method thus provide a cost effective sensing scheme. Proof-of
      principle demonstration by testing polyelectrolyte multilayer shows the
      sensitivity of ~4.0 mW/ng?mm-2 and the detection limit of ~5.35 pg/mm2.

PMID- 22418177
TI  - Comparison of the nonlinear transmission performance of quasi-Nyquist WDM and
      reduced guard interval OFDM.
AB  - The nonlinear transmission performance of quasi-Nyquist wavelength-division
      multiplexing (qN-WDM) and reduced guard interval orthogonal frequency-division
      multiplexing (RGI-OFDM) using polarization-division multiplexing quadrature phase
      shift-keying (PDM-QPSK) and quadrature amplitude modulation (PDM-QAM-8 and PDM
      QAM-16) with high information spectral densities have been compared for the first
      time, both by simulations and analytically. The results show that both systems
      are able to reach similar maximum transmission distances of approximately 6700km,
      2600km and 1100km over standard single-mode fibre for the spectral efficiencies
      of 3.43 bits/s/Hz, 5.25 bits/s/Hz and 7 bits/s/Hz respectively.

PMID- 22418178
TI  - High power density vertical-cavity surface-emitting lasers with ion implanted
      isolated current aperture.
AB  - We report on GaAs-based high power density vertical-cavity surface-emitting laser
      diodes (VCSELs) with ion implanted isolated current apertures. A continuous-wave
      output power of over 380 mW and the power density of 4.9 kW/cm<sup>2</sup> have
      been achieved at 15  degrees C from the 100-MUm-diameter aperture, which is the
      highest output characteristic ever reported for an ion implanted VCSEL. A high
      background suppression ratio of over 40 dB has also been obtained at the emission
      wavelength of 970 nm. The ion implantation technique provides an excellent
      current isolation in the apertures and would be a key to realize high power
      output from a VCSEL array.

PMID- 22418179
TI  - Waveguide structures for the visible and near-infrared wavelength regions in near
      stoichiometric lithium niobate formed by swift argon-ion irradiation.
AB  - We report the fabrication of a waveguide structure in a near-stoichiometric
      lithium niobate crystal using 200-MeV argon-ion irradiation at a fluence of 2 *
      10(12) ions/cm2. Guided modes were detected in the visible and near-infrared
      wavelength regions, suggesting that the waveguide can be used at fiber
      communications wavelengths. The refractive index profiles of the waveguide were
      reconstructed from the effective index functions. Micro-Raman spectra recorded in
      the waveguide layer and the substrate showed that the Li/Nb ratio was preserved
      in the waveguide layer after swift argon-ion irradiation.

PMID- 22418180
TI  - A hybrid CATV/OFDM long-reach passive optical network architecture.
AB  - A hybrid CATV/OFDM long-reach PON architecture is proposed and experimentally
      demonstrated. By multiplexing the OFDM and CATV signals in different frequency
      bands, the overall network structure is simplified and the available bandwidth
      for the OFDM signals is increased. Furthermore, by carefully adjusting the
      driving voltage of the employed CATV transmitter, the overall transmission
      performance can be optimized by eliminating a large amount of unwanted
      distortions. Unlike the current fiber optical CATV transport system in which the
      CATV signals need to be amplified in every 30 ~40 km transmission span, the
      proposed architecture has successfully extended the transmission span to 60 km.
      This can practically remove the needs of electrical power provisioning and
      monitoring between the central office (CO) and each local exchange (LE). Good
      transmission performances of carrier-to-noise ratio (CNR), composite second-order
      (CSO), composite triple beat (CTB) and bit error rate (BER) were obtained for the
      transmitted CATV and OFDM signals. All of these experimental results prove the
      practice and efficiency of the proposed architecture in providing simplicity and
      extended reach services to customers.

PMID- 22418181
TI  - Thermo-optic characteristics and switching power limit of slow-light photonic
      crystal structures on a silicon-on-insulator platform.
AB  - Employing a semi-analytic approach, we study the influence of key structural and
      optical parameters on the thermo-optic characteristics of photonic crystal
      waveguide (PCW) structures on a silicon-on-insulator (SOI) platform. The power
      consumption and spatial temperature profile of such structures are given as
      explicit functions of various structural, thermal and optical parameters,
      offering physical insight not available in finite-element simulations. Agreement
      with finite-element simulations and experiments is demonstrated. Thermal
      enhancement of the air-bridge structure is analyzed. The practical limit of
      thermo-optic switching power in slow light PCWs is discussed, and the scaling
      with key parameters is analyzed. Optical switching with sub-milliwatt power is
      shown viable.

PMID- 22418182
TI  - Inner- and outer-scale effects on the scintillation index of an optical wave
      propagating through moderate-to-strong non-Kolmogorov turbulence.
AB  - By use of the generalized von Karman spectrum model that features both inner
      scale and outer scale parameters for non-Kolmogorov turbulence and the extended
      Rytov method that incorporates a modified amplitude spatial-frequency filter
      function under strong-fluctuation conditions, theoretical expressions are
      developed for the scintillation index of a horizontally propagating plane wave
      and spherical wave that are valid under moderate-to-strong irradiance
      fluctuations. Numerical results show that the obtained expressions also compare
      well with previous results in weak-fluctuation regimes. Based on these general
      models, the impacts of finite inner and outer scales on the scintillation index
      of an optical wave are examined under various non-Kolmogorov fluctuation
      conditions.

PMID- 22418183
TI  - Femtosecond diode-pumped solid-state laser with a repetition rate of 4.8 GHz.
AB  - We report on a diode-pumped Yb:KGW (ytterbium-doped potassium gadolinium
      tungstate) laser with a repetition rate of 4.8 GHz and a pulse duration of 396
      fs. Stable fundamental modelocking is achieved with a semiconductor saturable
      absorber mirror (SESAM). The average output power of this compact diode-pumped
      solid state laser is 1.9 W which corresponds to a peak power of 0.9 kW and the
      optical-to-optical efficiency is 36%. To the best of our knowledge, this is the
      femtosecond DPSSL with the highest repetition rate ever reported so far.

PMID- 22418184
TI  - Precise switching control of liquid crystalline microgears driven by circularly
      polarized light.
AB  - Liquid crystalline molecules carrying photopolymerizable end groups absorb photon
      energy via a two-photon process, enabling the photofabrication of 3D structures.
      In this work, we prepared microgears with different heights and tooth lengths.
      These birefringent microgears can be induced to rotate by circularly polarized
      light. Here, we demonstrate that the use of phase plate for switching between
      left- and right-handed polarization reverses the optically induced rotation while
      maintaining the same rotational frequency. Due to the precise switching control,
      these birefringent microgears have advantages over previous microrotors that are
      fabricated from non-birefringent light-curing resins.

PMID- 22418185
TI  - Progressive compressive imaging from Radon projections.
AB  - In this work we propose a unique sampling scheme of Radon Projections and a non
      linear reconstruction algorithm based on compressive sensing (CS) theory to
      implement a progressive compressive sampling imaging system. The progressive
      sampling scheme offers online control of the tradeoff between the compression and
      the quality of reconstruction. It avoids the need of a priori knowledge of the
      object sparsity that is usually required for CS design. In addition, the
      progressive data acquisition enables straightforward application of ordered
      subsets algorithms which overcome computational constraints associated with the
      reconstruction of very large images. We present, to the best of our knowledge for
      the first time, a compressive imaging implementation of megapixel size images
      with a compression ratio of 20:1.

PMID- 22418186
TI  - Monolithic integration of a nanomechanical resonator to an optical microdisk
      cavity.
AB  - We report a Silicon nano-opto-mechanical device in which a nanomechanical doubly
      clamped beam resonator is integrated to an optical microdisk cavity. Small
      flexural oscillations of the beam cause intensity modulations in the circulating
      optical field in the nearby microdisk cavity. By monitoring the corresponding
      fluctuations in the cavity transmission via a fiber-taper, one can detect these
      oscillations with a displacement sensitivity approaching 10 fm.Hz-1/2 at an input
      power level of 50 MUW. Both the in-plane and out-of-plane fundamental flexural
      resonances of the beam can be read out by this approach - the latter being
      detectable due to broken planar symmetry in the system. Access to multiple
      mechanical modes of the same resonator may be useful in some applications and may
      enable interesting fundamental studies.

PMID- 22418187
TI  - Lossless intensity modulation in integrated photonics.
AB  - We present a dynamical analysis of lossless intensity modulation in two different
      ring resonator geometries. In both geometries, we demonstrate modulation schemes
      that result in a symmetrical output with an infinite on/off ratio. The systems
      behave as lossless intensity modulators where the time-averaged output optical
      power is equal to the time-averaged input optical power.

PMID- 22418188
TI  - Fabrication of three-dimensional microfluidic channels inside glass using
      nanosecond laser direct writing.
AB  - We show that fabrication of three-dimensional microfluidic channels embedded in
      glass can be achieved by using a Q-switched, frequency-doubled Nd:YAG laser. The
      processing mainly consists of two steps: (1) formation of hollow microfluidic
      channels in porous glass immersed in Rhodamine 6G dissolved in water by
      nanosecond laser ablation; and (2) postannealing of the fabricated porous glass
      sample at 1120  degrees C for consolidation of the sample. In particular, a
      bilayer microfluidic structure is created in glass substrate using this technique
      for showcasing its capability of three-dimensional structuring.

PMID- 22418189
TI  - Direct generation of all-optical random numbers from optical pulse amplitude
      chaos.
AB  - We propose and theoretically demonstrate an all-optical method for directly
      generating all-optical random numbers from pulse amplitude chaos produced by a
      mode-locked fiber ring laser. Under an appropriate pump intensity, the mode
      locked laser can experience a quasi-periodic route to chaos. Such a chaos
      consists of a stream of pulses with a fixed repetition frequency but random
      intensities. In this method, we do not require sampling procedure and external
      triggered clocks but directly quantize the chaotic pulses stream into random
      number sequence via an all-optical flip-flop. Moreover, our simulation results
      show that the pulse amplitude chaos has no periodicity and possesses a highly
      symmetric distribution of amplitude. Thus, in theory, the obtained random number
      sequence without post-processing has a high-quality randomness verified by
      industry-standard statistical tests.

PMID- 22418190
TI  - Impact of signal-to-noise ratio in a hyperspectral sensor on the accuracy of
      biophysical parameter estimation in case II waters.
AB  - Errors in the estimated constituent concentrations in optically complex waters
      due solely to sensor noise in a spaceborne hyperspectral sensor can be as high as
      80%. The goal of this work is to elucidate the effect of signal-to-noise ratio
      (SNR) on the accuracy of retrieved constituent concentrations. Large variations
      in the magnitude and spectral shape of the reflectances from coastal waters
      complicate the impact of SNR on the accuracy of estimation. Due to the low
      reflectance of water, the actual SNR encountered for a water target is usually
      quite lower than the prescribed SNR. The low SNR can be a significant source of
      error in the estimated constituent concentrations. Simulated and measured at
      surface reflectances were used in this study. A radiative transfer code, Tafkaa,
      was used to propagate the at-surface reflectances up and down through the
      atmosphere. A sensor noise model based on that of the spaceborne hyperspectral
      sensor HICO was applied to the at-sensor radiances. Concentrations of chlorophyll
      a, colored dissolved organic matter, and total suspended solids were estimated
      using an optimized error minimization approach and a few semi-analytical
      algorithms. Improving the SNR by reasonably modifying the sensor design can
      reduce estimation uncertainties by 10% or more.

PMID- 22418191
TI  - 3-D integrated heterogeneous intra-chip free-space optical interconnect.
AB  - This paper presents the first chip-scale demonstration of an intra-chip free
      space optical interconnect (FSOI) we recently proposed. This interconnect system
      provides point-to-point free-space optical links between any two communication
      nodes, and hence constructs an all-to-all intra-chip communication fabric, which
      can be extended for inter-chip communications as well. Unlike electrical and
      other waveguide-based optical interconnects, FSOI exhibits low latency, high
      energy efficiency, and large bandwidth density, and hence can significantly
      improve the performance of future many-core chips. In this paper, we evaluate the
      performance of the proposed FSOI interconnect, and compare it to a waveguide
      based optical interconnect with wavelength division multiplexing (WDM). It shows
      that the FSOI system can achieve significantly lower loss and higher energy
      efficiency than the WDM system, even with optimistic assumptions for the latter.
      A 1*1-cm2 chip prototype is fabricated on a germanium substrate with integrated
      photodetectors. Commercial 850-nm GaAs vertical-cavity-surface-emitting-lasers
      (VCSELs) and fabricated fused silica microlenses are 3-D integrated on top of the
      substrate. At 1.4-cm distance, the measured optical transmission loss is 5 dB,
      the crosstalk is less than -20 dB, and the electrical-to-electrical bandwidth is
      3.3 GHz. The latter is mainly limited by the 5-GHz VCSEL.

PMID- 22418192
TI  - Enhancing electromagnetically-induced transparency in a multilevel broadened
      medium.
AB  - Electromagnetically-induced transparency has become an important tool to control
      the optical properties of dense media. However, in a broad class of systems, the
      interplay between inhomogeneous broadening and the existence of several excited
      levels may lead to a vanishing transparency. Here, by identifying the underlying
      physical mechanisms resulting in this effect, we show that transparency can be
      strongly enhanced. We thereby demonstrate a 5-fold enhancement in a room
      temperature vapor of alkali-metal atoms via a specific shaping of the atomic
      velocity distribution.

PMID- 22418193
TI  - Synchronization in small networks of time-delay coupled chaotic diode lasers.
AB  - Topologies of two, three and four time-delay-coupled chaotic semiconductor lasers
      are experimentally and theoretically found to show new types of synchronization.
      Generalized zero-lag synchronization is observed for two lasers separated by long
      distances even when their self-feedback delays are not equal. Generalized sub
      lattice synchronization is observed for quadrilateral geometries while the
      equilateral triangle is zero-lag synchronized. Generalized zero-lag
      synchronization, without the limitation of precisely matched delays, opens
      possibilities for advanced multi-user communication protocols.

PMID- 22418194
TI  - Novel yellow-emitting phosphors of Ca5M4(VO4)6 (M=Mg, Zn) with isolated VO4
      tetrahedra.
AB  - The self-activated yellow-emitting phosphors of vanadates Ca5M4(VO4)6 (M = Mg,
      Zn) were synthesized via the solid-state reaction route. The formation of single
      phase compound with garnet structure was verified through X-ray diffraction (XRD)
      studies. The excitation and emission spectra and the thermal quenching of
      luminescence intensities were measured. The different luminescence properties of
      Ca5Mg4(VO4)6 and Ca5Zn4(VO4)6 phosphors were presented, e.g., the spectra shift,
      the luminescence lifetimes, the absolute quantum efficiency, the color
      coordinates and the Stokes shift. This deference was discussed on the base of the
      relationship between the micro-structure and the charge transfer transitions in
      [VO4]3- groups in the lattices. Ca5Mg4(VO4)6 could be suggested to be a potential
      yellow-emitting phosphor for the application on near-UV excited white LEDs.

PMID- 22418195
TI  - 2x2 MIMO-OFDM Gigabit fiber-wireless access system based on polarization division
      multiplexed WDM-PON.
AB  - We propose a spectral efficient radio over wavelength division multiplexed
      passive optical network (WDM-PON) system by combining optical polarization
      division multiplexing (PDM) and wireless multiple input multiple output (MIMO)
      spatial multiplexing techniques. In our experiment, a training-based zero forcing
      (ZF) channel estimation algorithm is designed to compensate the polarization
      rotation and wireless multipath fading. A 797 Mb/s net data rate QPSK-OFDM signal
      with error free (<1 * 10(5)) performance and a 1.59 Gb/s net data rate 16QAM-OFDM
      signal with BER performance of 1.2 * 10(2) are achieved after transmission of
      22.8 km single mode fiber followed by 3 m and 1 m air distances, respectively.

PMID- 22418196
TI  - Color effects from scattering on random surface structures in dielectrics.
AB  - We show that cheap large area color filters, based on surface scattering, can be
      fabricated in dielectric materials by replication of random structures in
      silicon. The specular transmittance of three different types of structures,
      corresponding to three different colors, have been characterized. The angle
      resolved scattering has been measured and compared to predictions based on the
      measured surface topography and by the use of non-paraxial scalar diffraction
      theory. From this it is shown that the color of the transmitted light can be
      predicted from the topography of the randomly textured surfaces.

PMID- 22418197
TI  - Tapered 4.7 MUm quantum cascade lasers with highly strained active region
      composition delivering over 4.5 watts of continuous wave optical power.
AB  - A strain-balanced, Al0.7In0.22As/In0.72Ga0.28As/InP quantum cascade laser
      structure, designed for light emission at 4.7um using the non-resonant extraction
      design approach, was grown by molecular beam epitaxy. Laser devices were
      processed in tapered buried heterostructure geometry and then mounted on AlN/SiC
      composite submounts using hard solder. A 10 mm long laser with 7.5um-wide central
      section tapered up to 20um at laser facets generated over 4.5W of single-ended
      CW/RT optical power at 283K. Maximum wallplug efficiency of 16.3% for this laser
      was reached at 4W level. Reliability of over 2,000h has been demonstrated for an
      air-cooled system delivering optical power of 3W in a collimated beam with
      overall system efficiency exceeding 10%.

PMID- 22418198
TI  - Mechanism of nanograting formation on the surface of fused silica.
AB  - Nanograting inscription with a tightly focused femtosecond beam on the surface of
      fused silica was studied. The width and spacing of grooves are shown to decrease
      with the increase of the number of overlapped shots in both stationary and
      scanning cases. We propose a model to explain this behavior, based on both the so
      called nanoplasmonic model and the incubation effect.

PMID- 22418199
TI  - Smart Q-switching for single-pulse generation in an erbium-doped fiber laser.
AB  - In this paper, we report an active Q-switching of an erbium-doped fiber laser
      with special modulation functions and novel laser geometry. We experimentally
      demonstrate that using such a smart Q-switch approach, Q-switch ripple-free
      pulses with Gaussian-like shape and 17.3 ns width can be easily obtained. The
      idea behind the smart Q-switch is to suppress one of two laser waves contra
      propagating along the fiber cavity, which arises after Q-cell opening, and to
      eliminate the minor sub-pulses.

PMID- 22418200
TI  - Diffraction effects for interferometric measurements due to imaging aberrations.
AB  - Aspheric surfaces are often measured using interferometers with null correctors,
      either refractive or diffractive. The use of null correctors allows high accuracy
      in the measurement, but also introduces imaging aberrations, such as mapping
      distortion and field curvature. These imaging aberrations couple with diffraction
      effects and limit the accuracy of the measurements, causing high frequency
      features in the surface under test to be filtered out and creating artifacts near
      boundaries, especially at edges. We provide a concise methodology for analyzing
      these effects using the astigmatic field curves to define the aberration, and
      showing how this couples with diffraction as represented by the Talbot effect and
      Fresnel edge diffraction. The resulting relationships are validated with both
      computer simulations and direct measurements from an interferometer with CGH null
      corrector.

PMID- 22418201
TI  - Spectroscopic ellipsometry as an optical probe of strain evolution in
      ferroelectric thin films.
AB  - Heteroepitaxial strain in ferroelectric thin films is known to have a significant
      impact on both their low and high frequency dielectric properties. In this paper,
      we use ex-situ spectroscopic ellipsometry to study the strain evolution with film
      thickness, and strain relaxation in ferroelectric Ba0.5Sr0.5<TiO3 epitaxial films
      grown on single crystal substrates. For films grown on MgO substrates, a critical
      thickness for strain relaxation is observed. In addition, studies of
      Ba0.5Sr0.5<TiO3 films grown on different single crystal substrates reveal that
      the strain relaxation rate can be inferred from changes in the optical
      properties. Using this information, we show that the optical constants of
      Ba0.5Sr0.5<TiO3 can be readily tuned via strain engineering.

PMID- 22418202
TI  - Impurity concentration and temperature dependence of the refractive indices of
      Er3+ doped ceramic Y2O3.
AB  - The refractive indices and thermo-optic coefficients for varying concentrations
      of Er3+ doped polycrystalline yttria were measured at a variety of wavelengths
      and temperatures. A Lorenz oscillator model was employed to model the room
      temperature indices and thermo-optic coefficients were calculated based on
      temperature dependent index measurements from 0.45 to 1.064 microns. Some
      consequences relating to thermal lensing are discussed.

PMID- 22418203
TI  - Direct measurement of bend-induced mode deformation in large-mode-area fibers.
AB  - In 1976 Marcuse developed an equivalent index model to predict the effects of
      bending in waveguides, and predicted deformation of the spatial modes in bent
      optical fibers. Perturbative approaches have been previously applied and tested
      to predict the behavior of single- and few-moded-fibers. However, much more
      significant mode deformation has been predicted for large-mode-area fibers than
      for single- or few-moded-fibers. In this paper, the spatial profiles of modes
      deformed by bending in large-mode-area fibers are measured for the first time. A
      finite difference method employing the equivalent index model is used to
      calculate the modes of the helical fiber, which show an offset that is twice as
      large as that predicted for single-mode fiber, and mode compression that is five
      times greater. These calculated results are compared to the experimental data,
      yielding significantly better agreement than previous perturbative approaches.

PMID- 22418204
TI  - Step-index optical waveguide produced by multi-step ion implantation in LiNbO3.
AB  - The refractive indexes, material attenuation and damage fractions of a multi-step
      ion implanted Lithium Niobate (LiNbO3) waveguide were analyzed as functions of
      the annealing temperatures. An almost flat damage depth profile was designed to
      reduce the uncertainties related to the indexes profile shape, thus providing a
      better test-case for the characterizations. The measurements performed on the
      fabricated optical waveguides confirmed the predicted step-index profiles showing
      that the light is confined inside the damaged layer. The low measured attenuation
      (less than 0.8 dB/cm @ 632.8 nm) makes the obtained waveguide attractive for
      device fabrication.

PMID- 22418205
TI  - Photonic ADC: overcoming the bottleneck of electronic jitter.
AB  - Accurate conversion of wideband multi-GHz analog signals into the digital domain
      has long been a target of analog-to-digital converter (ADC) developers, driven by
      applications in radar systems, software radio, medical imaging, and communication
      systems. Aperture jitter has been a major bottleneck on the way towards higher
      speeds and better accuracy. Photonic ADCs, which perform sampling using ultra
      stable optical pulse trains generated by mode-locked lasers, have been
      investigated for many years as a promising approach to overcome the jitter
      problem and bring ADC performance to new levels. This work demonstrates that the
      photonic approach can deliver on its promise by digitizing a 41 GHz signal with
      7.0 effective bits using a photonic ADC built from discrete components. This
      accuracy corresponds to a timing jitter of 15 fs - a 4-5 times improvement over
      the performance of the best electronic ADCs which exist today. On the way towards
      an integrated photonic ADC, a silicon photonic chip with core photonic components
      was fabricated and used to digitize a 10 GHz signal with 3.5 effective bits. In
      these experiments, two wavelength channels were implemented, providing the
      overall sampling rate of 2.1 GSa/s. To show that photonic ADCs with larger
      channel counts are possible, a dual 20-channel silicon filter bank has been
      demonstrated.

PMID- 22418206
TI  - Quantum-correlated two-photon transitions to excitons in semiconductor quantum
      wells.
AB  - The dependence of the excitonic two-photon absorption on the quantum correlations
      (entanglement) of exciting biphotons by a semiconductor quantum well is studied.
      We show that entangled photon absorption can display very unusual features
      depending on space-time-polarization biphoton parameters and absorber density of
      states for both bound exciton states as well as for unbound electron-hole pairs.
      We report on the connection between biphoton entanglement, as quantified by the
      Schmidt number, and absorption by a semiconductor quantum well. Comparison
      between frequency-anti-correlated, unentangled and frequency-correlated biphoton
      absorption is addressed. We found that exciton oscillator strengths are highly
      increased when photons arrive almost simultaneously in an entangled state. Two
      photon-absorption becomes a highly sensitive probe of photon quantum correlations
      when narrow semiconductor quantum wells are used as two-photon absorbers.

PMID- 22418207
TI  - All-fiber laser source for CARS microscopy based on fiber optical parametric
      frequency conversion.
AB  - A novel approach for an all-fiber mono-laser source for CARS microscopy is
      presented. An Yb-fiber laser generates 100 ps pulses, which later undergo
      narrowband in-fiber frequency conversion based on degenerate four-wave-mixing.
      The frequency conversion is optimized to access frequency shifts between 900 and
      3200cm-1, relevant for vibrational imaging. Inherently synchronized pump and
      Stokes pulses are available at one fiber end, readily overlapped in space and
      time. The source is applied to CARS spectroscopy and microscopy experiments in
      the CH-stretching region around 3000cm-1. Due to its simplicity and maintenance
      free operation, the laser scheme holds great potential for bio-medical
      applications outside laser laboratories.

PMID- 22418208
TI  - Multi-band slow light metamaterial.
AB  - In this paper, a multi-band slow light metamaterial is presented and
      investigated. The metamaterial unit cell is composed of three cut wires of
      different sizes and parallel to each other. Two transparency windows induced by
      two-two overlaps of absorption bands of three cut wires are observed. The multi
      band transmission characteristics and the slow light properties of metamaterial
      are verified by numerical simulation, which is in a good agreement with
      theoretical predictions. The impacts of structure parameters on transparency
      windows are also investigated. Simulation results show the spectral properties
      can be tuned by adjusting structure parameters of metamaterial. The equivalent
      circuit model and the synthesis method of the multi-band slow light metamaterial
      are presented. It is seen from simulation results that the synthesis method
      accurately predicts the center frequency of the multi-band metamaterial, which
      opens a door to a quick and accurate construction for multi-band slow light
      metamaterial.

PMID- 22418209
TI  - High-dispersive mirrors for high power applications.
AB  - We report on the development and manufacturing of two different types of high
      dispersive mirrors (HDM). One of them provides a record value for the group delay
      dispersion (GDD) of -4000 fs2 and covers the wavelength range of 1027-1033 nm,
      whereas the other one provides -3000 fs2 over the wavelength range of 1020-1040
      nm. Both of the fabricated mirrors exhibit a reflectance of >99.9% and are well
      suited for intracavity applications. Mirrors of the second type have been
      successfully employed in a Kerr-lens mode-locked Yb:YAG thin-disk oscillator for
      the generation of 200-fs pulses with multi-10-W average power.

PMID- 22418210
TI  - Tunable Mid-infrared ZnGeP2 RISTRA OPO pumped by periodically-poled Rb:KTP
      optical parametric master-oscillator power amplifier.
AB  - A laser-diode pumped Q-switched single-frequency Nd:YAG MOPA operating at 100 Hz
      was used to generate tunable mid-infrared radiation between 6.27 um and 8.12 um
      by employing a cascaded parametric arrangement consisting of degenerate
      parametric master-oscillator power amplifier using a large aperture periodically
      poled Rb:KTiOPO4 which in turn pumped a ZnGeP2 (ZGP) nonplanar RISTRA OPO. The
      noncollinear ZGP RISTRA tuning behavior is elucidated. The device is aimed for
      minimally invasive surgery applications at 6.45 um where the peak power of 193 kW
      in 5 ns pulses is demonstrated.

PMID- 22418211
TI  - Terahertz emission from Indium Oxide films grown on MgO substrates using sub
      bandgap photon energy excitation.
AB  - Indium oxide (In2O3) films grown by thermal oxidation on MgO substrates were
      optically excited by femtosecond laser pulses having photon energy lower than the
      In2O3 bandgap. Terahertz (THz) pulse emission was observed using time domain
      spectroscopy. Results show that THz emission saturates at an excitation fluence
      of ~400 nJ/cm2. Even as two-photon absorption has been excluded, the actual
      emission mechanism has yet to be confirmed but is currently attributed to
      carriers due to weak absorption from defect levels that are driven by a strain
      field at the interface of the substrate and the grown film.

PMID- 22418212
TI  - Ultra-precise characterization of LCLS hard X-ray focusing mirrors by high
      resolution slope measuring deflectometry.
AB  - We present recent results on the inspection of a first diffraction-limited hard X
      ray Kirkpatrick-Baez (KB) mirror pair for the Coherent X-ray Imaging (CXI)
      instrument at the Linac Coherent Light Source (LCLS). The full KB system -
      mirrors and holders - was under inspection by use of high resolution slope
      measuring deflectometry. The tests confirmed that KB mirrors of 350mm aperture
      length characterized by an outstanding residual figure error of <1 nm rms has
      been realized. This corresponds to the residual figure slope error of about
      0.05urad rms, unprecedented on such long elliptical mirrors. Additional
      measurements show the clamping of the mirrors to be a critical step for the final
      - shape preserving installation of such outstanding optics.

PMID- 22418213
TI  - Local-field enhancement effect on the nonlinear optical response of gold-silver
      nanoplanets.
AB  - We report on the nonlinear optical properties of Au-Ag nanoplanets produced by
      ion implantation and irradiation in silica, experimentally investigated by means
      of the single beam z-scan technique. The measurements provided experimental
      evidence of the intense local-field enhancement effect theoretically demonstrated
      for these plasmonic nanosystems. In particular, this has a dramatic impact on
      their nonlinear absorption behavior and results in a tunable changeover from
      reverse saturable absorption to saturable absorption by slightly varying the pump
      intensity and in the possibility to activate and observe nonlinear phenomena of
      the electron dynamics otherwise unaccessible in the intensity range that can be
      employed to study these materials. Finally, for the nanoplanet configuration we
      found a dramatic decrease of the intensity-dependent absorption coefficient,
      which could be very promising for obtaining optical gain materials.

PMID- 22418214
TI  - Mode coupling dynamics and communication strategies for multi-core fiber systems.
AB  - The propagation dynamics of 7-core multi-core fibers (MCFs) with identical and
      three-types of cores are analytically derived based on the coupled-mode theory.
      The mode coupling dynamics can be aperiodic with transmission distance for MCF
      with identical cores. For MCFs with heterogeneous cores, it is found that even
      though signals from different core groups will not couple with each other, the
      coupling within their own group is significantly affected by the presence of
      other core groups. Joint signal processing techniques to mitigate mode coupling
      induced-cross-talks such as least mean square (LMS) algorithm and maximum
      likelihood (ML) detection are investigated and corresponding transmission
      performance are determined for coherent as well as intensity modulated formats.
      It is shown that aperiodic mode coupling in intensity modulated systems induces
      cross-talks that are difficult to eliminate through signal processing. The
      analytical insights may help in optimizing MCF designs and corresponding signal
      processing techniques for future high capacity MCF transmission systems.

PMID- 22418215
TI  - Performance of a novel LED lamp arrangement to reduce SNR fluctuation for multi
      user visible light communication systems.
AB  - This paper investigates the performance of our recently proposed LED lamp
      arrangement to reduce the SNR fluctuation from different locations in the room
      for multi-user visible light communications. The LED lamp arrangement consists of
      4 LED lamps positioned in the corners and 12 LED lamps spread evenly on a circle.
      Our studies show that the SNR fluctuation under such a LED lamp arrangement is
      reduced from 14.5 dB to 0.9 dB, which guarantees that users can obtain almost
      identical communication quality, regardless of their locations. After time domain
      zero-forcing (ZF) equalization, the BER performances and channel capacities of
      100-Mbit/s and 200-Mbit/s bipolar on-off-keying (OOK) signal with most
      significant inter-symbol interference (ISI) are very close to that of the channel
      without any ISI caused by this LED lamp arrangement.

PMID- 22418216
TI  - Coronagraphs adapted to atmosphere conditions.
AB  - In this paper we show new ways to improve the performance of ground-based
      coronagraphy. We introduce adaptive coronagraphic masks whose profile is a binary
      version of the instantaneous atmospherically degraded star image. We also propose
      the hyper-Gaussian profile masks obtained by averaging adaptive masks. In
      addition, adaptive Lyot stops and hyper-Gaussian Lyot stops are analyzed.
      Computer simulations show that all these masks outperform the circular hard-edged
      mask and that a proper mask and stop combination significantly reduces the
      angular separation at which a faint companion can be detected.

PMID- 22418217
TI  - 3D scanning characteristics of an amorphous silicon position sensitive detector
      array system.
AB  - The 3D scanning electro-optical characteristics of a data acquisition prototype
      system integrating a 32 linear array of 1D amorphous silicon position sensitive
      detectors (PSD) were analyzed. The system was mounted on a platform for imaging
      3D objects using the triangulation principle with a sheet-of-light laser. New
      obtained results reveal a minimum possible gap or simulated defect detection of
      approximately 350 MUm. Furthermore, a first study of the angle for 3D scanning
      was also performed, allowing for a broad range of angles to be used in the
      process. The relationship between the scanning angle of the incident light onto
      the object and the image displacement distance on the sensor was determined for
      the first time in this system setup. Rendering of 3D object profiles was
      performed at a significantly higher number of frames than in the past and was
      possible for an incident light angle range of 15  degrees  to 85  degrees .

PMID- 22418218
TI  - Optical coherence tomography for quality assessment of embedded microchannels in
      alumina ceramic.
AB  - Large-scale and cost-effective manufacturing of ceramic micro devices based on
      tape stacking requires the development of inspection systems to perform high
      resolution in-process quality control of embedded manufactured cavities, metal
      structures and defects. With an optical coherence tomography (OCT) system
      operating at 1.3 MUm and a dedicated automated line segmentation algorithm, layer
      thicknesses can be measured and laser-machined channels can be verified in
      alumina ceramics embedded at around 100 MUm depth. Monte Carlo simulations are
      employed to analyze the abilities of OCT in imaging of the embedded channels. The
      light scattering parameters required as input data for simulations are evaluated
      from the integrating sphere measurements of collimated and diffuse transmittance
      spectra using a reconstruction algorithm based on refined diffusion approximation
      approach.

PMID- 22418219
TI  - Broadband amplification by picosecond OPCPA in DKDP pumped at 515 nm.
AB  - On the quest towards reaching petawatt-scale peak power light pulses with few
      cycle duration, optical parametric chirped pulse amplification (OPCPA) pumped on
      a time scale of a few picoseconds represents a very promising route. Here we
      present an experimental demonstration of few-ps OPCPA in DKDP, in order to
      experimentally verify the feasibility of the scheme. Broadband amplification was
      observed in the wavelength range of 830-1310 nm. The amplified spectrum supports
      two optical cycle pulses, at a central wavelength of ~920 nm, with a pulse
      duration of 6.1 fs (FWHM). The comparison of the experimental results with our
      numerical calculations of the OPCPA process showed good agreement. These findings
      confirm the reliability of our theoretical modelling, in particular with respect
      to the design for further amplification stages, scaling the output peak powers to
      the petawatt scale.

PMID- 22418220
TI  - Side-illumination fluorescence critical angle: theory and application to F8BT
      doped polymer optical fibers.
AB  - In this work we have analyzed theoretically and experimentally the critical angle
      for the emission generated in doped polymer optical fibers as a function of
      different launching conditions by using the side-illumination fluorescence
      technique. A theoretical model has been developed in order to explain the
      experimental measurements. It is shown that both the theoretical and experimental
      critical angles are appreciably higher than the meridional critical angle
      corresponding to the maximum acceptance angle for a single source placed at the
      fiber axis. This increase changes the value of several important parameters in
      the performance of active fibers. The analysis has been performed in polymer
      optical fibers doped with a conjugated polymer.

PMID- 22418221
TI  - Optical trapping in an absorbing medium: from optical tweezing to thermal
      tweezing.
AB  - We report on optical trapping in a weakly absorbing medium, hemin, an iron
      containing porphyrin that is an important component of hemoglobin. By altering
      the hemin concentration we are able to control the amount of optical energy that
      is absorbed; changing the hemin concentration from <12 mg/ml to >45 mg/ml enables
      the onset of thermal trapping to be observed. By estimating the trap strength
      using two different methods we are readily able to differentiate between the
      optical trapping and thermal trapping regimes. We also deduce the rise in
      temperature that occurs within the laser focal volume: temperature changes of 5
      24 K are observed for laser power values of 10-90 mW for hemin concentrations of
      0-50 mg/ml.

PMID- 22418222
TI  - Simultaneous measurements of absorption spectrum and refractive index in a
      microfluidic system.
AB  - The characterization of dyes in various solvents requires determination of the
      absorption spectrum of the dye as well as the refractive index of the solvent.
      Typically, the refractive index of the solvent and the absorption spectrum of the
      solute are measured using separate experimental setups where significant liquid
      volumes are required. In this work the first optical measurement system that is
      able to do simultaneous measurements of the refractive index of the solvent and
      the spectral properties of the solute in a microscopic volume is presented. The
      laser dye Rhodamine 6G in glycerol is investigated, and the refractive index of
      the solution is monitored using the interference pattern of the light scattered
      off the channel, while its spectral properties is found by monitoring reflected
      light from the channel.

PMID- 22418223
TI  - Piston and tilt cophasing of segmented laser array using Shack-Hartmann sensor.
AB  - We describe a concept of detecting the piston and tilt errors with a Shack
      Hartmann sensor and correcting them simultaneously via a segmented deformable
      mirror (DM) in a two-dimensional laser array. The concept in coherent beam
      combination (CBC) is demonstrated by both simulation and experiment. The
      simulative results show only two iterations are enough to correct the random
      initial phase errors in the steady condition. The experimental results confirm
      that this method works effectively in a dynamic condition. The study represents
      that the Shack-Hartmann sensor can extract any piston error in -pi ~pi, which
      means the concept is an arbitrary phasing technique for a laser array.

PMID- 22418224
TI  - Broadband metamaterial absorber based on coupling resistive frequency selective
      surface.
AB  - We report the design, fabrication, and measurement of a broadband metamaterial
      absorber, which consists of lossy frequency selective surface (FSS) and a
      metallic ground plane separated by a dielectric layer. The compact single unit
      cell of the FSS contains crisscross and fractal square patch which couple with
      each other. Both qualitative analysis by equivalent circuit and accurate numeric
      calculation show that the coupling between the crisscross and the fractal square
      patch can enhance the bandwidth with the reflectivity below -10dB in the
      frequency range of 2-18GHz by producing a third absorption null. In the end, the
      designed absorber was realized by experiment.

PMID- 22418225
TI  - High efficiency half-wave retardation in diffracted light by coupled waves.
AB  - We demonstrate high-efficiency half-wave retardation in diffracted light in the
      2nd order Littrow mounting. The diffracting structure is a slanted crossed
      grating with subwavelength period in the direction of the second grating vector,
      which makes it possible to mix the polarization states of the input light inside
      the grating layer, and hence to create the half-wave retardation. We present an
      experimental result with 58.9 % diffraction efficiency and a near perfect half
      wave retardation. We explain the effect qualitatively using the classical coupled
      wave approach.

PMID- 22418226
TI  - Fundamental characteristics of degradation-recoverable solid-state DFB polymer
      laser.
AB  - A novel solid-state dye laser with degradation recovery was proposed and
      demonstrated. Polydimethylsiloxane was used as a nanoporous solid matrix to
      enable the internal circulation of dye molecules in the solid state. An internal
      circulation model for the dye molecules was also proposed and verified
      numerically by assuming molecular mobility and using a proposed diffusion
      equation. The durability of the laser was increased 20.5-fold compared with that
      of a conventional polymethylmethacrylate laser. This novel laser solves the low
      durability problem of dye-doped polymer lasers.

PMID- 22418227
TI  - Long vs. short-range orders in random subwavelength hole arrays.
AB  - We analyze the progressive introduction of disorder in periodic subwavelength
      hole arrays. Two models of disorder are discussed from their associated Fourier
      transforms and correlation functions. The optical transmission properties of the
      corresponding arrays are closely related with the evolutions of structure
      factors, as experimentally detailed. Remarkably, the optical properties of random
      arrays are not in general equal to those of the single hole as a result of short
      range correlations corresponding to hole-to-hole interactions. These correlations
      are due to packing constraints that are controlled through the careful generation
      of random patterns. For high density pattern, short-range order can take over
      long-range order associated with the periodic array.

PMID- 22418229
TI  - Speckle size of light scattered from 3D rough objects.
AB  - From scalar Helmholtz integral relation and by coordinate system transformation,
      this paper begins with a derivation of the far-zone speckle field in the
      observation plane perpendicular to the scattering direction from an arbitrarily
      shaped conducting rough object illuminated by a plane wave illumination, followed
      by the spatial correlation function of the speckle intensity to obtain the
      speckle size from the objects. Especially, the specific expressions for the
      speckle sizes of light backscattered from spheres, cylinders and cones are
      obtained in detail showing that the speckle size along one direction in the
      observation plane is proportional to the incident wavelength and the distance
      between the object and the observation plane, and is inverse proportional to the
      maximal illuminated dimension of the object parallel to the direction. In
      addition, the shapes of the speckle of the rough objects with different shapes
      are different. The investigation on the speckle size in this paper will be useful
      for the statistical properties of speckle from complicated rough objects and the
      speckle imaging to target detection and identification.

PMID- 22418228
TI  - Split-spectrum amplitude-decorrelation angiography with optical coherence
      tomography.
AB  - Amplitude decorrelation measurement is sensitive to transverse flow and immune to
      phase noise in comparison to Doppler and other phase-based approaches. However,
      the high axial resolution of OCT makes it very sensitive to the pulsatile bulk
      motion noise in the axial direction. To overcome this limitation, we developed
      split-spectrum amplitude-decorrelation angiography (SSADA) to improve the signal
      to-noise ratio (SNR) of flow detection. The full OCT spectrum was split into
      several narrower bands. Inter-B-scan decorrelation was computed using the
      spectral bands separately and then averaged. The SSADA algorithm was tested on in
      vivo images of the human macula and optic nerve head. It significantly improved
      both SNR for flow detection and connectivity of microvascular network when
      compared to other amplitude-decorrelation algorithms.

PMID- 22418230
TI  - Using photopolymerization to achieve tunable liquid crystal lenses with coaxial
      bifocals.
AB  - Liquid crystal (LC) lenses with circular hole-patterned electrodes possess the
      excellent capabilities of tunable focal lengths. In this paper, we demonstrate
      the performance of a specific LC lens with tunable coaxial bifocals (CB)
      synthesized via photopolymerization of LC cells. The characteristics of tunable
      CB are clearly exhibited when the voltage applied is continuously increased,
      eventually disappearing until only one focus is left when significantly higher
      voltages are applied. We simultaneously demonstrate two types of tunable CB LC
      lenses fabricated via different photocurable processes and determine their
      optical functions.

PMID- 22418231
TI  - High density fringes and phase behavior in birefringence dual frequency laser
      with multiple feedback.
AB  - The high density intensity fringes and phase behavior in birefringent dual
      frequency laser with multiple feedback are studied for the first time. It was
      discovered that the fringes of output intensity are made of bipolar pulses with
      symmetric external cavity feedback and the fringe density is as high as compared
      to the conventional feedback. The high density cosine-like fringes are obtained
      with asymmetric external cavity feedback by adjusting the tilt angle of the
      feedback mirror and the fringe density is about 22 times higher compared to the
      conventional feedback. Moreover, there is a phase difference between the two
      cosine-like fringes and the phase difference is varied with the change of the
      external cavity length. The experimental results and a theoretical analysis are
      presented in this work. These results offer a large increase in the resolution
      for the optical feedback interferometer with the birefringence dual frequency
      laser.

PMID- 22418232
TI  - Dispersion dependence of linewidth in actively mode-locked ring lasers.
AB  - We studied the spectral linewidth narrowing of wavelength-swept actively mode
      locked ring lasers (AMLLs). The numerical calculations for the static-state AMLL
      led us to predict that anomalous dispersion would narrows the linewidth. We
      examined the effect experimentally using AMLL setups for normal and anomalous
      dispersive cavities via the normal or inverse use of a linearly chirped fiber
      Bragg grating. The experiment indicated that the cavity with anomalous dispersion
      always generates narrower linewidth lasers than its normal dispersion equivalent.
      The cavity with anomalous dispersion also achieved a 0.08 nm linewidth. Using the
      anomalous dispersion setup, we observed instantaneous linewidth broadening during
      wavelength sweeping. Although the coherence of AMLL decreased drastically when
      the sweep rate became very rapid beyond a single roundtrip, narrow-linewidth
      lasing was observed within a single roundtrip. In summary, we demonstrated the
      use of 150 kHz wavelength sweeping with a 40-nm range and a 2.7-m short-length
      anomalous dispersion cavity.

PMID- 22418233
TI  - Laser lithographic approach to micro-optical freeform elements with extremely
      large sag heights.
AB  - Artificial compound eye cameras are an attractive approach to generate imaging
      systems of maximum miniaturization. Their thickness can be reduced by a factor of
      two in comparison to miniaturized single aperture cameras with the same pixel
      size and resolution. The imaging performance of these systems can be improved
      significantly by the use of micro-optical refractive freeform arrays (RFFA). Due
      to the complexity of these non-symmetric surface profiles with sag heights larger
      than 50 um in combination with extreme profile accuracies better than lambda/14
      (rms), there is no dedicated fabrication technology currently available. In the
      presented research, significant improvements in the fabrication of these elements
      with laser lithography were reached. Therefore, a laser lithographic process
      based on several coating steps in combination with a multiple exposure strategy
      was developed that is suitable for the fabrication of arbitrary freeform
      structures with sag heights up to 60 um. In order to minimize surface deviations
      caused by unavoidable process nonlinearities, a compensation strategy based on an
      empirical process model is used. The achievable accuracy of the proposed method
      and its limitations were investigated by fabricating a spherical micro lens array
      for demonstration. The fabricated elements possess a shape deviation of less than
      1.3 um (rms) and can be used as master structures for a subsequent replication
      process in order to realize a cost efficient mass production of artificial
      compound eye optics on wafer level.

PMID- 22418234
TI  - Experimental demonstration of light bending at optical frequencies using a non
      homogenizable graded photonic crystal.
AB  - Experimental results on light bending in a non-homogenizable graded photonic
      crystal operating at optical wavelengths are presented in this paper. A square
      lattice silicon on insulator photonic crystal made of a two-dimensional chirp of
      the air-hole filling factor is exploited to produce the bending effect in a near
      bandgap frequency range. The sensitivity of light paths to wavelength tuning is
      also exploited to show demultiplexing capability with low insertion loss (<2dB)
      and low crosstalk (~-20dB). This experimental demonstration opens opportunities
      for light manipulation using a generalized two-dimensional chirp of photonic
      crystal lattice parameters. It also constitutes an alternative solution to the
      use of photonic metamaterials combining dielectric and metallic materials with
      sub-wavelength unit cells.

PMID- 22418235
TI  - Modulation of the propagation speed of mechanical waves in silicon quantum dots
      embedded in a silicon-nitride film.
AB  - Using a vectorial picosecond self-diffraction method, we evaluate the
      modification of the speed of the sound in a silicon-nitride film containing
      silicon quantum dots prepared by remote plasma-enhanced chemical vapor
      deposition. Our non-contact technique is based on the stimulation of the
      electrostriction contribution to the nonlinearity of index exhibited by the
      sample in a multiwave mixing laser experiment. We identified the electronic
      birefringence using two of the incident beams to generate a self-diffraction
      signal, then, we modified the third order nonlinear response by means of the
      optical Kerr effect given by a phase-mismatched third beam which induced
      electrostriction. Our results indicated that the speed of the sound in a silicon
      nitride film can be simultaneously tailored by an electronic nonlinear refractive
      index, and by an electrostriction effect, both resulting from silicon quantum
      dots doping.

PMID- 22418236
TI  - Impressive laser intensity increase at the trailing stage of femtosecond laser
      filamentation in air.
AB  - The longitudinal distribution of the laser peak intensity inside a half meter
      long femtosecond laser filament in air is studied by measuring the signal ratio
      of two nitrogen fluorescence lines, 391 nm and 337 nm. The experimental results
      reveal that laser peak intensity initially remains almost constant (~4.3 * 10(13)
      W/cm2) inside the filament. However, before the end of the filament, surprisingly
      the laser intensity undergoes dramatic increase. A maximum intensity as high as
      2.8*10(14) W/cm2 could be reached. The experimental result is unexpected by the
      conventional intensity clamping scenario, according to which the laser peak
      intensity would feature low variation along a filament. The experimental result
      is then interpreted as being due to the generation of a short pulse at trailing
      stage of the filamentation with reduced diameter. This phenomenon might be of
      great interest owing to its potential application in high-order-harmonic
      generation and producing isolated single attosecond laser pulse through simple
      experimental approach.

PMID- 22418237
TI  - Slow-light-based variable symbol-rate silicon photonics DQPSK receiver.
AB  - We report a silicon DQPSK receiver whose symbol rate can be varied by a tunable
      one-bit delay line including an all-pass micro-ring slow-light device. It also
      consists of Si-wire waveguides with spot-size converters, optimized
      splitters/couplers, heater-controlled Mach-Zehnder attenuators and phase
      shifters, 90 degrees  hybrid with a low-loss crossing and balanced Ge
      photodiodes, all of which are fabricated by using CMOS-compatible process.
      Demodulation was confirmed at symbol-rates of 7.4 - 9.0 Gbaud, corresponding to
      bit-rates of 14.8 - 18.0 Gb/s.

PMID- 22418238
TI  - Easily fabricated, robust fiber-optic probe for weak fluorescence detection:
      modeling and initial experimental evaluation.
AB  - Detection of fluorescence from a low quantum yield fluorophore is challenging for
      a fiber-optic probe, especially when an inexpensive and robust construction is
      desired. We propose a conceptually straightforward theoretical model to optimize
      the factors affecting the fluorescence-capture capability of a bifurcated/coaxial
      fiber-optic probe. Experimentally we verify that such a probe, if optimized, can
      detect the fluorescence of a polymer fluorophore with a low quantum yield of
      0.0065.

PMID- 22418239
TI  - Development and validation of the Gothenburg Trismus Questionnaire (GTQ).
AB  - OBJECTIVES: To develop and validate a comprehensive, self-administered
      questionnaire for patients with limited ability to open the mouth, trismus.
      MATERIALS AND METHODS: We derived the Gothenburg Trismus Questionnaire (GTQ) from
      empirical evidence in the medical literature and interviews with medical experts
      as well as patients. The draft version was tested in a pilot study (n=18).
      Patients with a maximal incisal opening (MIO) of ?35mm were included. The study
      comprised patients with benign jaw-related conditions (n=51), patients treated
      for head and neck (H&N) cancer (n=78) and an age- and gender-matched control
      group without trismus (n=129). RESULTS: The GTQ instrument was well accepted by
      the patients, with satisfactory compliance and low rates of missing items. After
      item reduction, due to items not being conceptually relevant and/or low factor
      loadings, the GTQ demonstrated high internal consistency (Cronbach's alpha 0.72
      0.90), good construct validity and known-group validity. CONCLUSION: We developed
      a trismus-specific self-administered questionnaire, the GTQ, that showed good
      psychometric properties. We suggest this questionnaire, that has clear clinical
      relevance, to be adopted and used in clinical practice and in research, acting as
      a screening tool as well as an endpoint in intervention and jaw
      physiotherapy/rehabilitation studies.

PMID- 22418240
TI  - Impact of antihypertensive treatment on left ventricular systolic dyssynchrony in
      treatment-naive hypertensive patients.
AB  - Dyssynchrony is common in asymptomatic patients with hypertension. We sought to
      investigate the impact of antihypertensive treatment on dyssynchrony in patients
      with hypertension. A total of sixty patients who had uncomplicated hypertension
      that had never been treated (treatment-naive hypertensive patients) underwent
      echocardiographic evaluations of left ventricular (LV) dyssynchrony at baseline
      and after a 6-month treatment with antihypertensive drugs. The measured
      parameters were as follows: (1) the s.d. of 12 LV-segment time-to-peak systolic
      velocities (Ts-SD12), and (2) the maximal difference between peak systolic
      velocities of any 2 of the 12 segments (Ts-Max). Patients with Ts-SD12 >= 33 ms
      or Ts-Max >= 100 ms were regarded as having LV systolic dyssynchrony. Patients
      with systolic dyssynchrony (group 1, n = 29) and without systolic dyssynchrony
      (group 2, n = 31) were compared. Among the patients in group 1, antihypertensive
      treatment significantly improved LV systolic dyssynchrony (DeltaTs-SD12, -13.1
      ms; P<0.001 and DeltaTs-Max, -34.0 ms; P = 0.003), whereas it did not demonstrate
      additional benefit among group 2 patients. The change in LV systolic dyssynchrony
      was significantly associated with changes in the mean annulus E' velocity, mean
      annulus S' velocity and mean annulus E'/A' ratio, but not with changes in blood
      pressure and LV mass index. It is likely that chronic antihypertensive treatment
      could reverse the LV systolic dyssynchrony and simultaneously improve subclinical
      systolic and diastolic function in patients with hypertension and LV systolic
      dyssynchrony.

PMID- 22418241
TI  - Myofibrillogenesis regulator 1 induces hypertrophy by promoting sarcomere
      organization in neonatal rat cardiomyocytes.
AB  - Human myofibrillogenesis regulator 1, a novel 17-kDa protein, is closely involved
      in cardiac hypertrophy. We studied the molecular mechanism that links MR-1 to
      hypertrophic response. Hypertrophic hallmarks such as cell size and [(3)H]
      leucine incorporation were significantly increased when MR-1 was transfected into
      cardiomyocytes for 48 h. However, sarcomere organization was promoted when MR-1
      was transfected for 8 h. The finding that cardiac hypertrophy was induced long
      after increase of sarcomere organization indicates that the promoted sarcomere
      organization may be one of the crucial factors causing hypertrophy. Furthermore,
      when MR-1 was transfected into cardiomyocytes, the nuclear localization of
      myomesin-1 was shifted to the cytoplasm. Transfection with small ubiquitin-like
      modifier-1 (SUMO-1) mimicked the effect of MR-1 inducing translocation of
      myomesin-1. However, transfection with SUMO-1 in MR-1-silenced cardiomyocytes
      failed to induce translocation and sarcomere organization, even though SUMO-1
      expression was at the same level. Overexpression of MR-1 may induce cardiomyocyte
      hypertrophy via myomesin-1-mediated sarcomere organization.

PMID- 22418242
TI  - Paclitaxel plus bevacizumab in patients with chemoresistant relapsed small cell
      lung cancer as salvage treatment: a phase II multicenter study of the Hellenic
      Oncology Research Group.
AB  - INTRODUCTION: Therapeutic options for patients with relapsed, chemo-resistant
      small-cell lung cancer (SCLC) are limited. Since paclitaxel has demonstrated
      single-agent activity in the second-line setting of SCLC and angiogenesis seems
      to play an important role in the pathogenesis of the disease, a phase II trial
      was conducted in order to evaluate the efficacy and the tolerance of their
      combination in patients with relapsed, chemo-resistant SCLC. PATIENTS AND
      METHODS: Patients with an Eastern Cooperative Oncology Group (ECOG) performance
      status of 0-2 who experienced relapse within 3 months after completion of 1st
      line chemotherapy for SCLC were eligible. Patients were treated with paclitaxel
      (90 mg/m(2), days 1, 8 and 15) along with bevacizumab (10mg per kg of body
      weight, days 1 and 15) in cycles of 28 days. RESULTS: Thirty patients
      (male/female: 27/3) with a median age of 64 years and ECOG performance status
      0/1/2: 2/25/3 were enrolled. Nineteen patients (63.3%) had received at least two
      lines of prior treatment, 17 (56.7%) had undergone prior radiotherapy and nine
      (30%) had brain metastases at the time of study entry. The overall objective
      response rate was 20% (95% CI: 5.69-34.31%), including one complete remission,
      whereas the disease control rate was 36.7%. The median duration of response was
      2.5 months (range, 1.5-5.7), the median progression-free survival 2.7 months
      (range, 0.5-9.2) and the median overall survival 6.3 months (range, 0.5-17.9).
      Grades 3 and 4 toxicities were limited in neutropenia, diarrhea and fatigue.
      There was one case of non-fatal pulmonary embolism. CONCLUSIONS: The combination
      of paclitaxel with bevacizumab was feasible and active in this poor prognosis and
      heavily pretreated population of patients with advanced, chemoresistant SCLC,
      representing a valid therapeutic alternative which merits further evaluation.

PMID- 22418244
TI  - Expression of heme oxygenase-1 in non-small cell lung cancer (NSCLC) and its
      correlation with clinical data.
AB  - While changes in heme oxygenase (HO-1) in lung cancer have already been reported,
      conflicting results were obtained for enzyme expression in human lung cancer
      specimens. Therefore, the aim of this work was to study HO-1 expression in a
      large collection of human lung cancer samples. For this purpose, we analyzed the
      expression of HO-1 in an organized tissue microarray (TMA) and investigated its
      correlation with clinicopathological data. Ninety-six percent of tumor samples
      were positive for HO-1, and the expression of HO-1 was significantly higher in
      cancerous than in non-cancerous tissues. Importantly, HO-1 expression correlated
      with advanced stages and lymph node involvement. Additionally, quantitative RT
      PCR in 18 pairs of human lung carcinomas and their adjacent non-malignant tissues
      was performed. Our results demonstrate that HO-1 protein is upregulated in
      epithelial malignant cells in NSCLC and its expression is associated with higher
      stages of the disease. Additionally, different subcellular localization is
      observed between tumor and adjacent non-malignant tissues.

PMID- 22418243
TI  - Randomized phase II study of concurrent cisplatin/etoposide or
      paclitaxel/carboplatin and thoracic radiotherapy in patients with stage III non
      small cell lung cancer.
AB  - OBJECTIVE: To evaluate the activity and safety of concurrent thoracic
      radiotherapy (TRT) plus weekly paclitaxel/carboplatin (PC) regimen compared with
      widely used cisplatin/etoposide (PE) regimen in patients with unresectable stage
      III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were
      randomly assigned to receive the following treatments: PE arm, cisplatin
      (50mg/m(2)) on days 1, 8, 29, and 36 and etoposide (50 mg/m(2)) on days 1-5 and
      29-33 plus 60 Gy of TRT; PC arm, weekly concurrent carboplatin (AUC = 2) and
      paclitaxel (45 mg/m(2)) plus 60 Gy of TRT. RESULTS: A total of 65 patients were
      randomized (PE arm, n = 33; PC arm, n = 32). The 3-year overall survival (OS) was
      significantly better in the PE arm than in the PC arm (33.1% vs. 13%, P = .04).
      The incidence of Grade 3/4 neutropenia was 78.1% in the PE arm and 51.5% in the
      PC arm (P = .05). The rate of Grade 2 or greater radiation pneumonitis was 25% in
      the PE arm and 48.5% in the PC arm (P = .09). CONCLUSIONS: Compared to PE
      regimen, weekly PC regimen cannot be recommended since it failed to achieve an
      improvement in either OS or PFS.

PMID- 22418245
TI  - Napsin A is an independent prognostic factor in surgically resected
      adenocarcinoma of the lung.
AB  - INTRODUCTION: Napsin A is regarded as a marker of lung adenocarcinoma. However,
      no comprehensive analyses of napsin A-positive lung ADCs or the prognostic
      significance of napsin A expression have been reported to date. METHODS: 110
      primary lung adenocarcinoma cases were analyzed for clinicopathologic parameters,
      including overall survival, stage, histology, napsin A and TTF-1 expression, EGFR
      mutation, and ALK rearrangement. RESULTS: Napsin A-positive adenocarcinomas were
      significantly more prevalent among tumors characterized as relatively small (p =
      0.023), non-solid predominant (p < 0.001), non-mucinous/enteric (p < 0.001),
      positive for TTF-1 expression (p < 0.001), and positive for EGFR mutation (p =
      0.001). Multivariate analysis of overall survival demonstrated that the absence
      of napsin A was an independent prognostic factor for reduced survival time (p =
      0.002). CONCLUSION: Clinicopathologic characteristics associated with napsin A
      positive lung ADC are similar to and overlap with those of TTF-1-positive ADCs.
      The absence of napsin A is an independent poor prognostic factor in surgically
      resected adenocarcinoma. Further studies are necessary to determine the role of
      napsin A in the progression of lung adenocarcinoma.

PMID- 22418246
TI  - Pulsatile control of rotary blood pumps: Does the modulation waveform matter?
AB  - OBJECTIVE: Mechanical support of a failing heart is typically performed with
      rotary blood pumps running at constant speed, which results in a limited control
      on cardiac workload and nonpulsatile hemodynamics. A potential solution to
      overcome these limitations is to modulate the pump speed to create pulses. This
      study aims at developing a pulsatile control algorithm for rotary pumps, while
      investigating its effect on left ventricle unloading and the hemodynamics.
      METHODS: The CentriMag (Levitronix GmbH, Zurich, Switzerland) rotary blood pump
      was implanted in 5 sheep and cannulated from the ventricular apex to the
      descending aorta. A modified controller was connected to the pump yielding direct
      speed control via analog voltage. Pump speed modulation patterns, including sine,
      saw tooth, triangle, and square waveforms with 2 different phase shifts, were
      synchronized with heartbeat. Various hemodynamic parameters, such as left
      ventricular pressure and volume, coronary flow, and arterial pressure, were
      analyzed to examine the influence of pump support. RESULTS: The pump speed
      modulation significantly affected left ventricular pressure and volume and
      arterial pressure, whereas coronary flow was not influenced by pump support mode.
      Stroke work in the pulsatile modes varied from 69% to 91% of baseline value and
      from 74% to 96% of constant speed value. Consequently, cardiac workload can be
      adjusted to provide relaxation, which may lead to myocardial recovery.
      CONCLUSIONS: A synchronized pulsing rotary blood pump offers a simple and
      powerful control modality for heart unloading. This technique provides pulsatile
      hemodynamics, which is more physiologic than continuous blood flow and may be
      useful for perfusion of the other organs.

PMID- 22418247
TI  - Current status of endoscopic vein harvest in cardiac and peripheral vascular
      surgery.
AB  - Endoscopic harvesting of the saphenous vein (EVH) has been shown to minimize the
      morbidity associated with saphenous vein harvest for either coronary artery
      bypass or lower extremity bypass. However, the long-term benefit of a bypass
      procedure is predicated on conduit patency. Several studies suggest decreased
      patency with EVH compared with open vein harvest. Possible reasons for this
      discrepancy have been investigated by microscopic, electron microscopic, and
      functional studies of venous endothelium and contractile function of harvested
      veins with conflicting results. This review details the results of these studies.
      In addition, the clinical results of coronary bypass graft and lower extremity
      bypass with open vein harvest and EVH are described in regard to early wound
      complications and short- and long-term patency.

PMID- 22418248
TI  - Coronary artery disease in South Asians.
AB  - It is well established that South Asians living in the western world have a
      higher burden of cardiovascular disease than other ethnicities. Additionally,
      South Asians develop cardiovascular disease at a younger age, have a more
      aggressive form of coronary artery disease, and a higher overall mortality. This
      predilection seems to be multifactorial and includes a combination of traditional
      and emerging risk factors with an absence of ethnic-specific prevention and
      control measures. Future direction points toward ongoing research with the aim of
      discovering technology for earlier detection. Additionally, coronary artery
      disease in South Asians could be addressed by increasing awareness, modifying
      health beliefs through health-promotion strategies, and instituting ethnic
      specific control measures including appropriate and early pharmacological
      intervention.

PMID- 22418249
TI  - An update on diastolic dysfunction.
AB  - Diastolic dysfunction refers to abnormal diastolic filling properties of the left
      ventricle regardless of whether systolic function is normal or the patient has
      symptoms. Diastolic heart failure (HF), or more accurately, HF with preserved
      systolic function, is a distinct clinical entity characterized by the presence of
      the triad of impaired diastolic function, normal systolic function (left
      ventricular ejection fraction > 50%), and symptoms of HF. Patients with HF with
      preserved systolic function are frequently symptomatic from both acute and
      chronic elevations in left ventricular end-diastolic pressure and/or left atrial
      pressure.

PMID- 22418250
TI  - Growth mechanism and properties of InGaN insertions in GaN nanowires.
AB  - We demonstrate the strong influence of strain on the morphology and In content of
      InGaN insertions in GaN nanowires, in agreement with theoretical predictions
      which establish that InGaN island nucleation on GaN nanowires may be
      energetically favorable, depending on In content and nanowire diameter. EDX
      analyses reveal In inhomogeneities between the successive dots but also along the
      growth direction within each dot, which is attributed to compositional pulling.
      Nanometer-resolved cathodoluminescence on single nanowires allowed us to probe
      the luminescence of single dots, revealing enhanced luminescence from the high In
      content top part with respect to the lower In content dot base.

PMID- 22418251
TI  - The hour of transition into luteolysis in horses and cattle: a species
      comparison.
AB  - Hourly blood sampling in both horses and cattle indicate that the transition
      between the end of preluteolysis and the beginning of luteolysis occurs within 1
      h, as manifested by a change in progesterone concentrations. Each species
      presents a separate temporality enigma on the relationship between pulses of a
      prostaglandin (PG) F2alpha metabolite (PGFM) and the hour of the progesterone
      transition. In horses, relatively small pulses of PGFM occur during preluteolysis
      (before transition) and at transition. Oxytocin, but not estradiol, increases and
      decreases concomitantly with the small PGFM pulse at transition but not with
      previous pulses and may account for the initiation of luteolysis during the small
      PGFM pulse. In cattle, the last PGFM pulse of preluteolysis occurs hours before
      transition (e.g., 4 h), and the next pulse occurs well after transition (e.g., 9
      h); unlike in horses, a PGFM pulse does not occur at transition. During the last
      PGFM pulse before transition, progesterone concentration decreases during the
      ascending portion of the PGFM pulse. Concentration then rebounds in synchrony
      with an LH pulse. The rebound returns progesterone to the concentration before
      the PGFM pulse. During luteolysis, an LH-stimulated progesterone rebound may
      occur after the peak of a PGFM pulse, but progesterone does not return to the
      concentration before the PGFM pulse. A similar LH-stimulated progesterone rebound
      does not occur in horses, and therefore progesterone fluctuations are more
      shallow in horses than in cattle.

PMID- 22418252
TI  - The magnetotransport properties of the intermetallic compound GdCu6.
AB  - We have studied the temperature and magnetic field dependence of the  electrical
      resistivity of GdCu(6) and have co-related the results with the temperature
      dependence of heat capacity and magnetization. The magnetoresistance of GdCu(6)
      is found to be positive both in the paramagnetic and antiferromagnetic regimes.
      Within the antiferromagnetic regime, the magnetoresistance is very high and
      increases to still higher values both with increasing field and decreasing
      temperature. In the paramagnetic regime the magnetoresistance continues to
      exhibit a finite positive value up to temperatures much higher than that
      corresponding to the antiferromagnetic to paramagnetic phase transition. We have
      shown through quantitative analysis that both the temperature dependences of
      resistivity and heat capacity indicate the presence of spin fluctuations within
      the paramagnetic regime of GdCu(6). The field dependence of electrical
      resistivity indicates that the positive magnetoresistance in the paramagnetic
      phase is not related to the orbital motion of the conduction electrons in a
      magnetic field (the Kohler rule). In contrast, our analysis indicates that these
      spin fluctuations are responsible for the positive magnetoresistance observed
      within this paramagnetic regime. The nature of the field dependence of electrical
      resistivity is found to be qualitatively similar both in the antiferromagnetic
      and paramagnetic regimes, which probably indicates that spin fluctuations in the
      paramagnetic regime are of the antiferromagnetic type.

PMID- 22418253
TI  - The sharpest tools in the box? Quantitative analysis of conodont element
      functional morphology.
AB  - Conodonts have been considered the earliest skeletonizing vertebrates and their
      mineralized feeding apparatus interpreted as having performed a tooth function.
      However, the absence of jaws in conodonts and the small size of their
      oropharyngeal musculature limits the force available for fracturing food items,
      presenting a challenge to this interpretation. We address this issue
      quantitatively using engineering approaches previously applied to mammalian
      dentitions. We show that the morphology of conodont food-processing elements was
      adapted to overcome size limitations through developing dental tools of
      unparalleled sharpness that maximize applied pressure. Combined with observations
      of wear, we also show how this morphology was employed, demonstrating how
      Wurmiella excavata used rotational kinematics similar to other conodonts,
      suggesting that this occlusal style is typical for the clade. Our work places
      conodont elements within a broader dental framework, providing a phylogenetically
      independent system for examining convergence and scaling in dental tools.

PMID- 22418255
TI  - Evolutionary demography of iteroparous plants: incorporating non-lethal costs of
      reproduction into integral projection models.
AB  - Understanding the selective forces that shape reproductive strategies is a
      central goal of evolutionary ecology. Selection on the timing of reproduction is
      well studied in semelparous organisms because the cost of reproduction (death)
      can be easily incorporated into demographic models. Iteroparous organisms also
      exhibit delayed reproduction and experience reproductive costs, although these
      are not necessarily lethal. How non-lethal costs shape iteroparous life histories
      remains unresolved. We analysed long-term demographic data for the iteroparous
      orchid Orchis purpurea from two habitat types (light and shade). In both the
      habitats, flowering plants had lower growth rates and this cost was greater for
      smaller plants. We detected an additional growth cost of fruit production in the
      light habitat. We incorporated these non-lethal costs into integral projection
      models to identify the flowering size that maximizes fitness. In both habitats,
      observed flowering sizes were well predicted by the models. We also estimated
      optimal parameters for size-dependent flowering effort, but found a strong
      mismatch with the observed flower production. Our study highlights the role of
      context-dependent non-lethal reproductive costs as selective forces in the
      evolution of iteroparous life histories, and provides a novel and broadly
      applicable approach to studying the evolutionary demography of iteroparous
      organisms.

PMID- 22418254
TI  - Sounds like a winner: voice pitch influences perception of leadership capacity in
      both men and women.
AB  - It is well known that non-human animals respond to information encoded in vocal
      signals, and the same can be said of humans. Specifically, human voice pitch
      affects how speakers are perceived. As such, does voice pitch affect how we
      perceive and select our leaders? To answer this question, we recorded men and
      women saying 'I urge you to vote for me this November'. Each recording was
      manipulated digitally to yield a higher- and lower-pitched version of the
      original. We then asked men and women to vote for either the lower- or higher
      pitched version of each voice. Our results show that both men and women select
      male and female leaders with lower voices. These findings suggest that men and
      women with lower-pitched voices may be more successful in obtaining positions of
      leadership. This might also suggest that because women, on average, have higher
      pitched voices than men, voice pitch could be a factor that contributes to fewer
      women holding leadership roles than men. Additionally, while people are free to
      choose their leaders, these results clearly demonstrate that these choices cannot
      be understood in isolation from biological influences.

PMID- 22418256
TI  - Alternative mechanisms alter the emergent properties of self-organization in
      mussel beds.
AB  - Theoretical models predict that spatial self-organization can have important,
      unexpected implications by affecting the functioning of ecosystems in terms of
      resilience and productivity. Whether and how these emergent effects depend on
      specific formulations of the underlying mechanisms are questions that are often
      ignored. Here, we compare two alternative models of regular spatial pattern
      formation in mussel beds that have different mechanistic descriptions of the
      facilitative interactions between mussels. The first mechanism involves a reduced
      mussel loss rate at high density owing to mutual protection between the mussels,
      which is the basis of prior studies on the pattern formation in mussels. The
      second mechanism assumes, based on novel experimental evidence, that mussels feed
      more efficiently on top of mussel-generated hummocks. Model simulations point out
      that the second mechanism produces very similar types of spatial patterns in
      mussel beds. Yet the mechanisms predict a strikingly contrasting effect of these
      spatial patterns on ecosystem functioning, in terms of productivity and
      resilience. In the first model, where high mussel densities reduce mussel loss
      rates, patterns are predicted to strongly increase productivity and decrease the
      recovery time of the bed following a disturbance. When pattern formation is
      generated by increased feeding efficiency on hummocks, only minor emergent
      effects of pattern formation on ecosystem functioning are predicted. Our results
      provide a warning against predictions of the implications and emergent properties
      of spatial self-organization, when the mechanisms that underlie self-organization
      are incompletely understood and not based on the experimental study.

PMID- 22418257
TI  - Are stress responses to geomagnetic storms mediated by the cryptochrome compass
      system?
AB  - A controversial body of literature demonstrates associations of geomagnetic
      storms (GMS) with numerous cardiovascular, psychiatric and behavioural outcomes.
      Various melatonin hypotheses of GMS have suggested that temporal variation in the
      geomagnetic field (GMF) may be acting as an additional zeitgeber (a temporal
      synchronizer) for circadian rhythms, with GMS somehow interfering with the
      hypothesized system. The cryptochrome genes are known primarily as key components
      of the circadian pacemaker, ultimately involved in controlling the expression of
      the hormone melatonin. Cryptochrome is identified as a clear candidate for
      mediating the effect of GMS on humans, demonstrating the prior existence of
      several crucial pieces of evidence. A distinct scientific literature demonstrates
      the widespread use of geomagnetic information for navigation across a range of
      taxa. One mechanism of magnetoreception is thought to involve a light-dependent
      retinal molecular system mediated by cryptochrome, acting in a distinct
      functionality to its established role as a circadian oscillator. There is
      evidence suggesting that such a magnetosense--or at least the vestiges of it--may
      exist in humans. This paper argues that cryptochrome is not acting as secondary
      geomagnetic zeitgeber to influence melatonin synthesis. Instead, it is
      hypothesized that the cryptochrome compass system is mediating stress responses
      more broadly across the hypothalamic-pituitary-adrenal (HPA) axis (including
      alterations to circadian behaviour) in response to changes in the GMF. Two
      conceptual models are outlined for the existence of such responses--the first as
      a generalized migrational/dispersal strategy, the second as a stress response to
      unexpected signals to the magnetosense. It is therefore proposed that GMS lead to
      disorientation of hormonal systems in animals and humans, thus explaining the
      effects of GMS on human health and behaviour.

PMID- 22418258
TI  - A performance-based cost to honest signalling in male green anole lizards (Anolis
      carolinensis).
AB  - Sexual signals are considered costly to produce and maintain under the handicap
      paradigm, and the reliability of signals is in turn thought to be maintained by
      these costs. Although previous studies have investigated the costly nature of
      signal production, few have considered whether honesty might be maintained not by
      the costliness of the signal itself, but by the costs involved in producing the
      signalled trait. If such a trait is itself costly to produce, then the burden of
      energetic investment may fall disproportionately on that trait, in addition to
      any costs of signal maintenance that may also be operating. Under limited
      resource conditions, these costs may therefore be great enough to disrupt an
      otherwise reliable signal-to-trait relationship. We present experimental evidence
      showing that dietary restriction decouples the otherwise honest relationship
      between a signal (dewlap size) and a whole-organism performance trait (bite
      force) in young adult male Anolis carolinensis lizards. Specifically, while
      investment in dewlap size is sustained under low-resource condition relative to
      the high-resource treatment, investment in bite force is substantially lower.
      Disruption of the otherwise honest dewlap size to bite force relationship is
      therefore driven by costs associated with the expression of performance rather
      than the costs of signal production in A. carolinensis.

PMID- 22418259
TI  - Kinetic mechanism of fuculose-1-phosphate aldolase from the hyperthermophilic
      archaeon Methanococcus jannaschii.
AB  - Fuculose-1-phosphate aldolase (FucA) is a useful biocatalyst with potential
      applications in chiral synthesis. In this study, the overall kinetic mechanism of
      FucA from the archaeon Methanococcus jannaschii was studied. The K(m) values of
      dihydroxyacetone phosphate (DHAP) and dl-glyceraldehyde were 0.09 and 0.74 mM,
      respectively. Dead-end inhibition by trimethyl phosphonoacetate and dl-threose
      were competitive and uncompetitive with respect to DHAP and dl-glyceraldehyde.
      Inhibition patterns obtained using reaction products were noncompetitive vs. DHAP
      and competitive vs. dl-glyceraldehyde. The equilibrium constant was 8.309*10(-3)
      M as assessed by varying the [DHAP]/[product] ratio at a fixed dl-glyceraldehyde
      concentration and by measuring the change in DHAP concentration after equilibrium
      was reached. This constant is consistent with the K(eq) value obtained from (13)C
      NMR (15.625*10(-3) M). The resultant inhibition kinetics may suggest the insights
      of kinetic mechanism of the FucA catalyzed reaction.

PMID- 22418260
TI  - Biosensor analyzer for BOD index express control on the basis of the yeast
      microorganisms Candida maltosa, Candida blankii, and Debaryomyces hansenii.
AB  - The parameters of biosensors based on the yeast strains Candida maltosa VKM Y
      2359, Candida blankii VKM Y-2675, and Debaryomyces hansenii VKM Y-2482 for
      biochemical oxygen demand (BOD) detection are compared. The catalytic activity of
      the strains was analyzed in relation to the growth phase. The possibility of
      using D. hansenii as a basis for receptor element of a biosensor for BOD
      detection in municipal and biotechnological wastewaters was shown.

PMID- 22418261
TI  - Comparative study of semi-specific Aeromonas hydrophila and universal Pseudomonas
      fluorescens biosensors for BOD measurements in meat industry wastewaters.
AB  - Aeromonas hydrophila P69.1 (A. hydrophila) was used to construct a semi-specific
      biosensor to estimate biochemical oxygen demand (BOD) in high fat and grease
      content wastewaters. A. hydrophila cells were grown in fat containing medium to
      induce necessary enzymes for transport and degradation of fatty substances.
      Universal biosensor based on non-specific Pseudomonas fluorescens P75 (P.
      fluorescens) was used to conduct comparison experiments. Biosensors were
      calibrated using OECD synthetic wastewater and steady-state method, subsequently
      several experiments with synthetic and industrial wastewaters were conducted. A
      linear range up to 45 mg l(-1) BOD(7) was gained using A. hydrophila biosensor,
      in comparison to 40 mg l(-1) BOD(7) obtained using P. fluorescens biosensors. The
      lower limit of detection was 5 mg l(-1) BOD(7). Service life of A. hydrophila and
      P. fluorescens biosensors were 110 and 115 days, respectively. The response time
      of the biosensors depended on the BOD(7) of measuring solution and was up to 20
      min when analyzing different wastewaters. Both biosensors underestimated BOD in
      meat industry wastewater from 43% up to 71%, but more accurate results could be
      obtained with A. hydrophila biosensor. Semi-specific A. hydrophila biosensor was
      able to measure proportion of fat found in wastewater sample, while other
      refractory compounds remained undetectable to both biosensors.

PMID- 22418262
TI  - Amperometric glucose biosensor utilizing FAD-dependent glucose dehydrogenase
      immobilized on nanocomposite electrode.
AB  - Amperometric glucose biosensors utilizing commercially available FAD-dependent
      glucose dehydrogenases from two strains of Aspergillus species are described.
      Enzymes were immobilized on nanocomposite electrode consisting of multi-walled
      carbon nanotubes by entrapment between chitosan layers. Unlike the common glucose
      oxidase based biosensor, the presented biosensors appeared to be O(2)
      independent. The optimal amount of enzymes, working potential and pH value of
      working media of the glucose biosensors were determined. The biosensor utilizing
      enzyme isolated from Aspergillus sp. showed linearity over the range from 50 to
      960 MUM and from 70 to 620 MUM for enzyme from Aspergillus oryzae. The detection
      limits were 4.45 MUM and 4.15 MUM, respectively. The time of response was found
      to be 60 s. The biosensors showed excellent operational stability - no loss of
      sensitivity after 100 consecutive measurements and after the storage for 4 weeks
      at 4  degrees C in phosphate buffer solution. When biosensors were held in a
      dessicator at room temperature without use, they kept the same response ability
      at least after 6 months. Finally, the results obtained from measurements of
      beverages and wine samples were compared with those obtained with the enzymatic
      spectrophotometric and standard HPLC methods, respectively. Good correlation
      between results in case of analysis of real samples and good analytical
      performance of presented glucose biosensor allows to use presented concept for
      mass production and commercial use.

PMID- 22418263
TI  - Laccase catalysed oxidation of syringic acid: calorimetric determination of
      kinetic parameters.
AB  - Isothermal titration calorimetry (ITC) was used to study the oxidation of
      syringic acid by laccases from two different sources: Galerina sp. HC1 and
      Trametes versicolor. Total molar heat of reaction with both enzymes was similar
      (230 kJ/mol for Galerina laccase and 233 kJ/mol for Trametes laccase), and was
      independent of syringic acid concentration. The kinetic parameters of the
      reaction were calculated from the single injection assay by applying the
      nonlinear least squares fitting (NLSF) of experimental data to the Michaelis
      Menten equation. Higher values for V(max) were obtained with Galerina sp.
      laccase, whereas K(m) values were comparable for the two enzymes.

PMID- 22418264
TI  - Fructose metabolism of the purple non-sulfur bacterium Rhodospirillum rubrum:
      effect of carbon dioxide on growth, and production of bacteriochlorophyll and
      organic acids.
AB  - During fermentative metabolism, carbon dioxide fixation plays a key role in many
      bacteria regarding growth and production of organic acids. The present
      contribution, dealing with the facultative photosynthetic bacterium
      Rhodospirillum rubrum, reveals not only the strong influence of ambient carbon
      dioxide on the fermentative break-down of fructose but also a high impact on
      aerobic growth with fructose as sole carbon source. Both growth rates and biomass
      yield increased with increasing carbon dioxide supply in chemoheterotrophic
      aerobic cultures. Furthermore, intracellular metabolite concentration
      measurements showed almost negligible concentrations of the tricarboxylic acid
      cycle intermediates succinate, fumarate and malate under aerobic growth, in
      contrast to several metabolites of the glycolysis. In addition, we present a dual
      phase fed-batch process, where an aerobic growth phase is followed by an
      anaerobic production phase. The biosynthesis of bacteriochlorophyll and the
      secretion of organic acids were both affected by the carbon dioxide supply, the
      pH value and by the cell density at the time of switching from aerobic to
      anaerobic conditions. The formation of pigmented photosynthetic membranes and the
      amount of bacteriochlorophyll were inversely correlated to the secretion of
      succinate. Accounting the high biotechnological potential of R. rubrum,
      optimization of carbon dioxide supply is important because of the favored
      application of fructose-containing fermentable feedstock solutions in bio
      industrial processes.

PMID- 22418265
TI  - Immobilization of creatininase, creatinase and sarcosine oxidase on iron oxide
      nanoparticles/chitosan-g-polyaniline modified Pt electrode for detection of
      creatinine.
AB  - Commercial enzymes, creatininase (CA) from Pseudomonas sp, creatinase (CI) from
      Pseudomonas sp, sarcosine oxidase (SO) from Bacillus sp were co-immobilized onto
      iron oxide nanoparticles/chitosan-graft-polyaniline (Fe(3)O(4)-NPs/CHIT-g-PANI)
      composite film electrodeposited on surface of Pt electrode through glutaraldehyde
      coupling. Transmission electron microscopy (TEM) was used for characterization of
      Fe(3)O(4)-NPs. A creatinine biosensor was fabricated using Enzymes/Fe(3)O(4)
      NPs/CHIT-g-PANI/Pt electrode as working electrode, Ag/AgCl as reference electrode
      and Pt wire as auxiliary electrode. The enzyme electrode was characterized by
      cyclic voltammetry (CV), scanning electron microscopy (SEM), Fourier transform
      infrared (FTIR) spectroscopic and electrochemical impedance spectroscopy (EIS).
      The biosensor exhibited an optimum response within 2s at pH 7.5 and 30  degrees
      C, when polarized at 0.4V vs Ag/AgCl. The electrocatalytic response showed a
      linear dependence on creatinine concentration ranging from 1 to 800 MUM. The
      sensitivity of the biosensor was 3.9 MUA MUM(-1) cm(-2), with a detection limit
      of 1 MUM (S/N=3). Apparent Michaelis-Menton (K(m)) value for creatinine was 0.17
      mM. The biosensor showed only 10% loss in its initial response after 120 uses
      over 200 days, when stored at 4  degrees C. The biosensor measured creatinine in
      the serum of apparently healthy persons which correlated well with a standard
      colorimetric method (r=0.99).

PMID- 22418266
TI  - Cloning and characterization of a thermostable H2O-forming NADH oxidase from
      Lactobacillus rhamnosus.
AB  - NADH oxidase (Nox) catalyzes the conversion of NADH to NAD(+). A previously
      uncharacterized Nox gene (LrNox) was cloned from Lactobacillus rhamnosus and
      overexpressed in Escherichia coli BL21(DE3). Sequence analysis revealed an open
      reading frame of 1359 bp, capable of encoding a polypeptide of 453 amino acid
      residues. The molecular mass of the purified LrNox enzyme was estimated to be ~50
      kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and 100 kDa by
      gel filtration chromatography, suggesting that the enzyme is a homodimer. The
      enzyme had optimal activity at pH 5.6 and temperature 65  degrees C, and
      k(cat)/K(m) of 3.77*10(7) s(-1) M(-1), the highest ever reported. Heat
      inactivation studies revealed that LrNox had high thermostability, with a half
      life of 120 min at 80  degrees C. Molecular dynamics simulation studies shed
      light on the factors contributing to the high activity of LrNox. Although the
      properties of Nox from several microorganisms have been reported, this is the
      first report on the characterization of a recombinant H(2)O-forming Nox with high
      activity and thermostability. The characteristics of the LrNox enzyme could prove
      to be of interest in industrial applications such as NAD(+) regeneration.

PMID- 22418267
TI  - C-terminal truncation of glutamate decarboxylase from Lactobacillus brevis CGMCC
      1306 extends its activity toward near-neutral pH.
AB  - Glutamate decarboxylase (GAD) from Lactobacillus brevis is a very promising
      candidate for biosynthesis of GABA and various other bulk chemicals that can be
      derived from GABA. However, no structure of GAD of this origin has been reported
      to date, which limits enzyme engineering strategy to improve its properties for
      better use in production of GABA. Bacterial GAD exhibits an acidic pH optimum and
      there is often a sharp pH dependence. In the present work, site-directed
      mutagenesis was performed to delete the C-terminal residues of GAD to generate a
      mutant, designated as GADDeltaC, which exhibited extended activity toward near
      neutral pH compared to the wild type. Comparison of the UV-visible, fluorescence
      and Circular Dichroism spectra of the mutant with those of the wild type revealed
      that the microenvironment of the active site had been changed. Based on the
      homology model, we speculated that the substrate entrance was probably enlarged
      in GADDeltaC. These results provide evidence for the important role of C-terminal
      region in the pH-dependent regulation of enzyme activity, and the resulting
      mutant would be useful in a bioreactor for continuous production of GABA.

PMID- 22418268
TI  - Insulin resistance and diabetes mellitus in patients with chronic hepatitis C:
      spectators or actors?

PMID- 22418269
TI  - Synesthetic colors for Japanese late acquired graphemes.
AB  - Determinants of synesthetic color choice for the Japanese logographic script,
      Kanji, were studied. The study investigated how synesthetic colors for Kanji
      characters, which are usually acquired later in life than other types of
      graphemes in Japanese language (phonetic characters called Hiragana and Katakana,
      and Arabic digits), are influenced by linguistic properties such as phonology,
      orthography, and meaning. Of central interest was a hypothesized generalization
      process from synesthetic colors for graphemes, learned prior to acquisition of
      Kanji, to Kanji characters learned later. Results revealed that color choices for
      Kanji characters depend on meaning and phonological information. Some results
      suggested that colors are generalized from Hiragana characters and Arabic digits
      to Kanji characters via phonology and meaning, respectively. Little influence of
      orthographic information was observed. The findings and approach of this study
      contributes to a clarification of the mechanism underlying grapheme-color
      synesthesia, especially in terms of its relationship to normal language
      processing.

PMID- 22418270
TI  - Polymorphisms in cytotoxic T lymphocyte associated antigen-4 influence the rate
      of acute rejection after renal transplantation in 167 Chinese recipients.
AB  - Gene polymorphisms of cytotoxic T lymphocyte associated antigen 4 (CTLA4) play an
      influential role in the graft rejection and long-term clinical outcome of organ
      transplantation. We investigated the associations of five CTLA4 single nucleotide
      polymorphisms (SNPs) (rs733618T/C, rs4553808A/G, rs5742909C/T, rs231775G/A,
      rs3087243G/A) on the early acute rejection (AR) of Chinese deceased donor renal
      transplantation recipients. Genotyping of the CTLA4 SNPs was performed in 167
      deceased donor renal transplantation recipients. Each patient underwent a 6-month
      follow-up observation for AR. The incidence of AR during the 6 months post
      transplantation was 26.9% (45 out of 167 patients). Patients experiencing AR were
      found to have a higher frequency of the rs733618TT genotype and T allele (p=0.000
      and p=0.002, respectively). While the haplotype CACAG was merely observed in non
      AR group (corrected p=0.000), the frequency of haplotype TACGG was significantly
      higher in AR group than in non-AR group even after 50,000 permutation tests
      (corrected p=0.018). In conclusion, these polymorphisms statistically
      significantly associated with acute renal allograft rejection may be considered
      as a risk factor of AR in Chinese renal transplantation recipients except for
      haplotype CACAG as a protective one.

PMID- 22418271
TI  - Connectivity disruptions in resting-state functional brain networks in children
      with temporal lobe epilepsy.
AB  - Functional resting-state connectivity has been shown to be altered in certain
      adult epilepsy populations, but few connectivity studies have been performed on
      pediatric epilepsy patients. Here functional connectivity was measured in
      pediatric, non-lesional temporal lobe epilepsy patients with normal intelligence
      and compared with that in age and gender-matched healthy controls using the
      independent component analysis method. We hypothesized that children with non
      lesional temporal lobe epilepsy have disrupted functional connectivity within
      resting-state networks. Significant differences were demonstrated between the two
      groups, pointing to a decrease in connectivity. When the results were analyzed
      according to the interictal electroencephalogram findings, however, the
      connectivity disruptions were seen in different networks. In addition, increased
      connectivity and abnormally anti-correlated thalamic activity was detected only
      in the patients with abnormal electroencephalograms. In summary, connectivity
      disruptions are already to be seen at an early stage of epilepsy, and
      epileptiform activity seems to affect connectivity differently. The results
      indicate that interictal epileptiform activity may lead to reorganization of the
      resting-state brain networks, but further studies would be needed in order to
      understand the pathophysiology behind this phenomenon.

PMID- 22418272
TI  - Free choice access to multipoint wellness education and related services
      positively impacts employee wellness: a randomized and controlled trial.
AB  - OBJECTIVE: Examine effects of voluntary participation in employer-sponsored,
      multipoint wellness education programming on employee wellness. METHODS: A
      randomized and controlled design was used to organize 96 participants into an
      education + access group; an access-only group, and control group. Outcome
      measures were made at start and end of a 12-week intervention period. RESULTS:
      Education + access improved wellness knowledge, which, in turn, enhanced life
      satisfaction, employee morale, and energy, and nearly improved stress level.
      Those who received facility access without educational programming did not reap
      health benefits. Employees voluntarily used the fitness facility and healthy meal
      cards only 1.3 and 1.5 times per week, respectively. CONCLUSIONS: Participants
      made limited and likely inadequate use of wellness opportunities. As a result,
      physical health benefits (eg, blood pressure, fitness parameters) were not seen
      in the present study. However, multipoint wellness education resulted in
      psychosocial health benefits in 12 weeks.

PMID- 22418273
TI  - Results of a 100-point scale for evaluating job satisfaction and the Occupational
      Depression Scale questionnaire survey in workers.
AB  - OBJECTIVE: To evaluate the relationship between the score of job satisfaction and
      depression. METHODS: A total of 2737 workers (2198 men and 539 women)
      participated. A 100-point scale for evaluating job satisfaction and the
      Occupational Depression Scale were used. A logistic regression analysis was
      applied with adjustment for age. RESULTS: The mean age of the subjects was 42.2
      years for men and 36.0 years for women. When the group with the highest job
      satisfaction score was set as the control, the odds ratios and 95% confidence
      intervals for depression in the groups with the lowest and second lowest scores
      were 16.3 (7.51 to 35.2) and 5.90 (2.70 to 12.9) in men and 8.02 (1.78 to 36.1)
      and 5.68 (1.26 to 25.7) in women, respectively. CONCLUSIONS: Job satisfaction was
      significantly associated with the depressive state, and causality should be
      clarified by a follow-up study.

PMID- 22418274
TI  - Quantifying the value of worksite clinic nonoccupational health care services: a
      critical analysis and review of the literature.
AB  - OBJECTIVE: Confusion exists regarding the approach to quantifying employer value
      of worksite nonoccupational care. A literature review and analysis was performed
      to characterize and critically evaluate existing methods to quantify the value of
      these services. METHODS: PubMed was searched for publications describing
      measurement of value of nonoccupational worksite clinic services in US locations.
      Nineteen studies and two methodologic reviews met criteria for further analysis.
      RESULTS: Return-on-investment calculations were commonly based on the comparative
      cost-effectiveness of worksite clinic services relative to community health care.
      Only one study evaluated the impact of worksite clinics on health care cost trend
      among clinic users, and none assessed the impact on total health and productivity
      costs. CONCLUSIONS: Significant variability exists among current methods for
      calculating return on investment of nonoccupational worksite health care
      services; methodologic approaches are poorly aligned with employer health care
      cost containment objectives.

PMID- 22418275
TI  - Natural history of opioid dosage escalation post-injury: a cohort study of
      injured workers in the State of Louisiana.
AB  - OBJECTIVE: To determine the relationship between opioid dosage and claim
      duration. METHODS: Closure rates and morphine-equivalent dose were analyzed over
      a 7-year period for 11,394 lost-time claims filed with the Louisiana Workers'
      Compensation Corporation. RESULTS: The percentage of claims in which opioids were
      ever prescribed increased from 43.3% in year 1 to 80.8% in year 7 post-injury.
      The percentage of claims in which individuals were prescribed long-acting (LA)
      opioids increased from 5.2% to 29.6%, and the percentage of claims in which
      individuals were prescribed only short-acting (SA) opioids increased from 38.1%
      to 51.2%. Morphine-equivalent dose increased from 10.0 mg/day (year 1) to 143.2
      mg/day (year 7) for claims in which individuals were prescribed LA opioids. The
      average claim duration for claims in which individuals were prescribed no
      opioids, only SA opioids, and LA opioids was 415, 930, and 2025 days,
      respectively. CONCLUSION: Opioid dosage escalates as claims mature.

PMID- 22418277
TI  - FMCSA's medical review board: five years of progress in commercial driver medical
      examinations.
AB  - OBJECTIVE: To revise and update guidance recommendations to the Federal Motor
      Carrier Safety Administration for evaluating commercial drivers. METHODS: The
      Federal Motor Carrier Safety Administration's medical review board has addressed
      guidance for commercial drivers for the past 5 years. The processes for most
      topics involve comprehensive literature searches, evidence reports, medical
      expert panel reports, critique of the literature, testimony, and decision making.
      RESULTS: No quality literature evaluating risk of crash among commercial motor
      vehicle drivers was found for most medical conditions. Little literature was
      available for crash risk among all drivers. For select conditions, such as
      seizure disorders, obstructive sleep apnea, and narcolepsy, there is evidence of
      increased crash risk among the general driving population and evidence-based
      guidance is now available. CONCLUSIONS: Detailed guidance from the Medical Review
      Board is available for assessing commercial drivers with various disorders. Many
      challenges remain.

PMID- 22418276
TI  - Effects of exercise on systemic inflammatory, coagulatory, and cardiac autonomic
      parameters in an inhalational exposure study.
AB  - BACKGROUND: Intermittent moderate-intensity exercise is used in human
      inhalational exposure studies to increase the effective dose of air pollutants.
      OBJECTIVE: To investigate the inflammatory, coagulatory, and autonomic effects of
      intermittent moderate-intensity exercise. METHODS: We measured hemodynamic,
      electrocardiographic, inflammatory, and coagulatory parameters in peripheral
      blood of 25 healthy subjects across an exercise protocol that included running on
      a treadmill or pedaling a cycle ergometer for 30 minutes every hour over 4 hours
      in a climate-controlled chamber with a target ventilation of 20 L/min/m2 body
      surface area. RESULTS: Intermittent moderate-intensity exercise induced a
      systemic proinflammatory response characterized by increases in leukocyte counts,
      C-reactive protein, monocyte chemoattractant protein-1, and interleukin-6, but
      did not change coagulation tendency or heart rate variability. CONCLUSION:
      Interpretation of pollutant-induced inflammatory responses in inhalational
      exposure studies should account for signals and noises caused by exercise,
      especially when the effect size is small.

PMID- 22418278
TI  - Antimycobacterial activity of bisbenzylisoquinoline alkaloids from Tiliacora
      triandra against multidrug-resistant isolates of Mycobacterium tuberculosis.
AB  - Bisbenzylisoquinoline alkaloids, tiliacorinine (1), 2'-nortiliacorinine (2), and
      tiliacorine (3), isolated from the edible plant, Tiliacora triandra, as well as a
      synthetic derivative, 13'-bromo-tiliacorinine (4), were tested against 59
      clinical isolates of multidrug-resistant Mycobacterium tuberculosis (MDR-MTB).
      The alkaloids 1-4 showed MIC values ranging from 0.7 to 6.2 MUg/ml, but they
      exhibited the MIC value at 3.1 MUg/ml against most MDR-MTB isolates. The present
      work suggests that bisbenzylisoquinoline alkaloids are potential new chemical
      scaffolds for antimycobacterial activity.

PMID- 22418279
TI  - Pimarane diterpenes from the fungus Epicoccum sp. HS-1 associated with
      Apostichopus japonicus.
AB  - Three new pimarane diterpenes (1, 2 and 3) as well as a known compound 4, were
      isolated from the marine-derived fungus HS-1 from Apostichopus japonicus. Their
      structures and relative stereochemistry of 1-3 were elucidated using a
      combination of NMR spectroscopy and CD. In the primary bioassay, compounds 1, 2
      and 4 inhibited the growth of KB and KBv200 with IC(50) of 3.51, 2.34 MUg/mL,
      20.74, 14.47 MUg/mL, and 3.86, 6.52 MUg/mL, respectively.

PMID- 22418280
TI  - Development of clickable active site-directed photoaffinity probes for gamma
      secretase.
AB  - We have developed clickable active site-directed photoaffinity probes for gamma
      secretase which incorporate a photoreactive benzophenone group and an alkyne
      handle for subsequent click chemistry mediated conjugation with azide-linked
      reporter tags for visualization (e.g., TAMRA-azide) or enrichment (e.g., biotin
      azide) of labeled proteins. Specifically, we synthesized clickable analogs of
      L646 (2) and L505 (3) and validated specific labeling to presenilin-1N-terminal
      fragment (PS1-NTF), the active site aspartyl protease component within the gamma
      secretase complex. Additionally, we were able to identify signal peptide
      peptidase (SPP) by Western blot analysis. Furthermore, we analyzed the photo
      labeled proteins in an unbiased fashion by click chemistry with TAMRA-azide
      followed by in-gel fluorescence detection. This approach expands the utility of
      gamma-secretase inhibitor (GSI) photoaffinity probes in that labeled proteins can
      be tagged with any number of azide-linked reporters groups using a single
      clickable photoaffinity probe for target pull down and/or fluorescent imaging
      applications.

PMID- 22418281
TI  - Regional mechanics determine collagen fiber structure in healing myocardial
      infarcts.
AB  - Following myocardial infarction, the mechanical properties of the healing infarct
      are an important determinant of heart function and the risk of progression to
      heart failure. In particular, mechanical anisotropy (having different mechanical
      properties in different directions) in the healing infarct can preserve pump
      function of the heart. Based on reports of different collagen structures and
      mechanical properties in various animal models, we hypothesized that differences
      in infarct size, shape, and/or location produce different patterns of mechanical
      stretch that guide evolving collagen fiber structure. We tested the effects of
      infarct shape and location using a combined experimental and computational
      approach. We studied mechanics and collagen fiber structure in cryoinfarcts in 53
      Sprague-Dawley rats and found that regardless of shape or orientation,
      cryoinfarcts near the equator of the left ventricle stretched primarily in the
      circumferential direction and developed circumferentially aligned collagen, while
      infarcts at the apex stretched similarly in the circumferential and longitudinal
      directions and developed randomly oriented collagen. In a computational model of
      infarct healing, an effect of mechanical stretch on fibroblast and collagen
      alignment was required to reproduce the experimental results. We conclude that
      mechanical environment determines collagen fiber structure in healing myocardial
      infarcts. Our results suggest that emerging post-infarction therapies that alter
      regional mechanics will also alter infarct collagen structure, offering both
      potential risks and novel therapeutic opportunities.

PMID- 22418282
TI  - Thermodynamic limit of the energy density in a crystal.
AB  - A pedagogical, semi-rigorous proof is presented for the existence of the
      thermodynamic (infinite-volume) limit of the energy per volume for an
      electrically neutral, metallic or nonmetallic crystal. The proof is based on the
      demonstration of the same for individual energy components, namely, the kinetic,
      Coulomb, and exchange contributions to the Hartree-Fock energy as well as the
      correlation contribution obtained by many-body perturbation or coupled-cluster
      theory.

PMID- 22418283
TI  - Molecular arrangement in water: random but not quite.
AB  - Water defines life on Earth from the cellular to the terrestrial level. Yet the
      molecular level arrangement in water is not well understood, posing problems in
      comprehending its very special chemical, physical and biological properties. Here
      we present high-resolution x-ray diffraction data for water clearly showing that
      its molecular arrangement exhibits specific correlations that are consistent with
      the presence of rings of H(2)O molecules linked together by hydrogen bonds into
      tetrahedral-like units from a continuous network. This level of molecular
      arrangement complexity is beyond what a simple 'two-state' model of water (Bernal
      and Fowler 1933 J. Chem. Phys.1 515-48) could explain. It may not be explained by
      the recently put forward 'chains-clusters of completely uncorrelated molecules'
      model (Wernet et al 2004 Science 304 995-9) either. Rather it indicates that
      water is homogeneous down to the molecular level where different water molecules
      form tetrahedral units of different perfection and/or participate in rings of
      different sizes, thus experiencing different local environments. The local
      diversity of this tetrahedral network coupled to the flexibility of the hydrogen
      bonds that hold it together may explain well the rich phase diagram of water and
      why it responds non-uniformly to external stimuli such as, for example,
      temperature and pressure.

PMID- 22418284
TI  - Comparing performance of three oscillating positive expiratory pressure devices
      at similar amplitude and frequencies of oscillations on displacement of mucus
      inside trachea during cough.
AB  - BACKGROUND: Performance of Flutter(r) (Axcan Scandipharm Inc, Birmingham, AL),
      Acapella(r) (Smiths Medicals Inc, Rockland, MA) and Quake(r) (Thayer Medical,
      Tucson, AZ) were compared at similar frequencies and amplitudes of oscillations
      at nine angles of the device in clearing simulated mucus inside a tracheal model
      (trachea) oriented at three angles with or without simulated constrictions in
      airway upstream of trachea. METHODS: Displacement of 0.4mL of simulated mucus
      prepared with viscoelastic properties similar to healthy individuals (syrup-like)
      or patients with COPD (gel-like) using locust bean gum(LBG) solution (0.38g LBG
      in 100mL water) cross-linked with 3mL or 12mL borax solution (0.02 molar),
      respectively were measured inside trachea during coughs of 300ms at low cough
      velocity (15+/-0.5m/s) generated using a computer controlled solenoid valve.
      Oscillations were superimposed on cough by connecting the oscillator device to
      the outlet of the trachea. RESULTS: Frequency and amplitude of oscillations
      generated by Quake and Acapella and resulting mucus displacement were independent
      of angle of oscillator, while amplitude of oscillations and resulting mucus
      displacement generated by Flutter, increased up to 30o upward and 20o downward
      angles of Flutter from horizontal but decreased significantly thereafter.
      Displacement with Quake increased significantly with frequencies of oscillations
      up to 25 Hz and decreased thereafter but increased with amplitudes of
      oscillations up to 22+/-4.7 m/s. Quake showed significantly larger displacements
      than Flutter and Acapella at equal frequencies and amplitudes (p<0.05).
      Displacements were significantly larger with trachea positioned 30o upwards than
      horizontal or 20o downwards (p<0.0001). Displacement was the greatest for gel
      like mucus than syrup-like (p<0.0001). Airway constrictions upstream resulted in
      enhanced displacement of mucus (p<0.0001). CONCLUSIONS: Mucus clearance can be
      significantly enhanced by coughing through oscillating positive expiratory
      devices that generate high amplitude oscillations at moderate frequencies,
      increasing frontal depths of mucus facing airflow and slightly increasing
      resistance to airflow in airways in COPD patients.

PMID- 22418285
TI  - [How to optimize the antiTNF alpha therapy in spondylitis?].
AB  - TNFalpha inhibitors have been a major advance in the treatment of
      spondyloarthropathies, having demonstrated their safety and efficacy, with higher
      response and survival rates than those observed in patients with rheumatoid
      arthritis. The fact that disease modifying anti-arthritic drugs (DMARD) have
      shown utility in the treatment of this disease, especially in the axial forms,
      gives them greater importance, since it is known that up to 30%of patients do not
      respond to treatment with non-steroidal anti-inflammatory drugs. However, we must
      take into account that these drugs are expensive and not without side effects, so
      it is necessary to optimize their use. We intend to review the use of antiTNF
      alpha in spondyloarthropathies and review the available evidence on strategies
      that can help with their rational use.

PMID- 22418286
TI  - The effect of zinc levels in a gold-based alloy on porcelain-metal bonding.
AB  - OBJECTIVES: The purpose of this study was to ascertain whether the amount of Zn
      in gold alloys contributes to porcelain-metal bonding. METHODS: Experiments were
      carried out using a commercial Pd-free gold alloy with a nominal composition of
      88.7 wt% Au, 9.49 wt% Pt, 1.5 wt% Zn, 0.1 wt% Mn, 0.2 wt% Rh, and 0.1 wt% Ir,
      which contains Zn and no other elements (In, Sn, Fe) known to affect porcelain
      metal bond strength. To establish the effect of oxidation of the metal surface,
      porcelain was applied both to preoxidized and to non-preoxidized metal specimens.
      The bond strength was evaluated by means of the ISO 9693: 1999 crack initiation
      test. A conventional gold alloy was used as a control. The elemental
      distributions at the porcelain/alloy interfaces were analyzed in cross section by
      electron probe microanalysis. Additionally, after the bond strength test, cross
      sections of the interfaces of the debonded specimens were microscopically
      analyzed to characterize the fracture mode. RESULTS: The Pd-free gold alloy
      joints showed significantly higher bond strength values than joints made with
      conventional gold alloy. Preoxidation treatment significantly increases the bond
      strength, in the preoxidized joints Zn was highly localized at the interface and
      diffused into the porcelain up to about 10 MUm from the interface, and the joint
      failed by cohesive fracture in the porcelain. In contrast, the non-preoxidized
      joint showed mainly adhesive fracture at the porcelain/alloy interface.
      SIGNIFICANCE: The presence of Zn in gold alloys plays a part in establishing
      chemical bonding thus improving the bond strength between porcelain and alloy.

PMID- 22418287
TI  - All-fiber low-loss connector for accessing both close cores of twin-core fiber.
AB  - A novel all-fiber connector is proposed for connecting each core of a twin-core
      fiber (TCF) to a single-core fiber (SCF) core simultaneously and accessing
      independently the both close cores of the TCF. The connector is mainly composed
      of two cascaded pieces of collinear four-core fiber (CFCF). The two close optical
      fields launched from the TCF are separated into two far apart optical fields, so
      that each optical field could be butt-coupled into one of the cores of one gemini
      fiber segment, which has two single-mode SCF pigtails. For the simulated example,
      the center distance of the two optical fields is increased from 16 MUm to more
      than 90 MUm, the cross-talk is -37 dB, and the power loss is 0.056 dB. The
      feasibility of the strategy is partially demonstrated experimentally by
      fabricating a CFCF by groove & stack & draw method and one gemini fiber segment
      with pigtails by flame-brushing technology.

PMID- 22418288
TI  - Polarized backlight with constrained angular divergence for enhancement of light
      extraction efficiency from wire grid polarizer.
AB  - Efficiency of liquid crystal displays highly depends on the amount of polarized
      light emerging from the backlight module. In this paper, a backlight architecture
      using a nanoimprint wire grid polarizer for polarization recycling is proposed
      and studied, in which the extraction efficiency of polarized light is the major
      concern. The backlight module is composed of the stack of a wire grid polarizer,
      a lenticular array and a light guide plate. The light guide plate features
      interleaving v-groove and trapezoidal ridge coated with aluminum on the top
      surface, and scattering dot array on the bottom. The angular divergence of
      emerging light from the light guide plate can be well constrained so as to
      exploit the angular range with the best transmission of polarized light for the
      wire grid polarizer. The prototype of a 2.5-inch module has demonstrated an
      angular divergence of 48 degrees . The overall extraction efficiency of polarized
      light enhanced by 21% and uniformity of 76% have been achieved.

PMID- 22418290
TI  - Genetic algorithm optimization for focusing through turbid media in noisy
      environments.
AB  - We introduce genetic algorithms (GA) for wavefront control to focus light through
      highly scattering media. We theoretically and experimentally compare GAs to
      existing phase control algorithms and show that GAs are particularly advantageous
      in low signal-to-noise environments.

PMID- 22418289
TI  - An automatic method for assembling a large synthetic aperture digital hologram.
AB  - A major issue so far for digital holography is the low spatial resolution
      generally achieved. The numerical aperture is limited by the area of currently
      available detectors, such as CCD sensors, which is significantly lower than that
      of a holographic plate. This is an even more severe constraint when IR sensors
      such as microbolometers are taken into account. In order to increase the
      numerical aperture of such systems, we developed an automatic technique which is
      capable of recording several holograms and of stitching them together, obtaining
      a digital hologram with a synthetic but larger numerical aperture. In this way we
      show that more detail can be resolved and a wider parallax angle can be achieved.
      The method is demonstrated for visible as well IR digital holography, recording
      and displaying large size objects.

PMID- 22418291
TI  - Generation of 110 W infrared and 65 W green power from a 1.3-GHz sub-picosecond
      fiber amplifier.
AB  - A fiber amplifier that generates nearly transform-limited sub-picosecond pulses
      and greater than 100 W average power at 1.3-GHz repetition rate is described.
      Modest stretching of the seed pulses allows the amplifier to be operated in the
      linear regime. The amplified and dechirped pulses exhibit excellent beam quality,
      and can be frequency-doubled to produce green pulses at 65 W average power.
      Detailed characterization of the performance is presented.

PMID- 22418292
TI  - Doubly resonant metallic nanostructure for high conversion efficiency of second
      harmonic generation.
AB  - The recent discovery of strong nonlinear emission in metallic nanostructures has
      offered possibilities for realization of functional nano photonic devices. Here,
      we demonstrate a novel design of a plasmonic nano device for high conversion
      efficiency of second harmonic generation. A 4 * 4 bowtie aperture array is
      fabricated to have both plasmonic resonance for local field enhancement of the
      fundamental wave and Fabry-Perot resonance for high transmission of second
      harmonic wave. Combining nano structures for exciting surface plasmon polariton
      and suppressing higher order diffraction and anti-reflection layer, we achieve a
      second harmonic conversion efficiency of 1.4 * 10(-8) that is nearly an order of
      magnitude larger than the results published in recent literatures. We also
      theoretically analyze evidences of the role of double resonances tuned to the
      fundamental wave and the second harmonic wave, resulting in the augmentation of
      second harmonic response approximately an order of magnitude greater than that
      without the help of the resonance.

PMID- 22418293
TI  - Phytoplankton light absorption of cultures and natural samples: comparisons using
      two spectrophotometers.
AB  - Here we present laboratory measurements of phytoplankton absorption for cultures
      and natural water samples using two different spectrophotometers, an Ultrapath
      system and a double beam spectrophotometer equipped with an integrating sphere
      (Lambda 850). The Ultrapath system provides simplified optics with high
      throughput efficiency, portability, and is relatively less expensive in
      comparison to conventional spectrophotometers. A more robust algorithm for
      correction of pathlength amplification (beta) for particles retained on filter
      paper was determined for Lambda 850 in comparison to the Ultrapath. The Lambda
      850 beta algorithm (ODs(lambda) = 0.405 [ODf(lambda)] + 0.475 [ODf(lambda)]2; r2
      = 0.973; n = 7395) showed species and size dependence as indicated by the LISST
      100X and HPLC chlorophyll-a concentration data. A better agreement was observed
      between the two spectrophotometers for filter paper measurements (r2 = 0.991;
      slope = 0.958; n = 130 for cultures and r2 = 0.978; slope = 0.957; n = 349 for
      natural samples), than for suspensions (r2 = 0.960; slope = 0.915; n = 92 for
      cultures and r2 = 0.960; slope = 0.921; n = 27 for natural samples). The
      differences in measurement of suspensions between the spectrophotometers could be
      attributed to volume scattering function and acceptance angle of the waveguide
      detector.

PMID- 22418294
TI  - IR microscopy utilizing intense supercontinuum light source.
AB  - Combining the molecular specificity of the infrared spectral region with high
      resolution microscopy has been pursued by researchers for decades. Here we
      demonstrate infrared supercontinuum radiated from an optical fiber as a promising
      new light source for infrared microspectroscopy. The supercontinuum light source
      has a high brightness and spans the infrared region from 1400 nm to 4000 nm. This
      combination allows contact free high resolution hyper spectral infrared
      microscopy. The microscope is demonstrated by imaging an oil/water sample with 20
      MUm resolution.

PMID- 22418295
TI  - Directional excitation of surface plasmon polaritons via nanoslits under varied
      incidence observed using leakage radiation microscopy.
AB  - Surface Plasmon Polaritons (SPPs) are excited at the interface between a thin
      gold film and air via the illumination of nanoslits etched into the film. The
      coupling efficiency to the two propagation directions away from the slits is
      determined by leakage radiation microscopy, when the angle of incidence of the
      pump beam is changed from 0 degrees  to 20 degrees . We find that preferential
      coupling of SPPs into one direction can be achieved for non-normal incidence in
      the case of single slits and slit pairs. The proportion of SPP excited into one
      direction can be in excess of 90%. We further provide a simple model of the
      process, and directly compare the performances of the two approaches.

PMID- 22418296
TI  - Talbot images of wavelength-scale amplitude gratings.
AB  - By means of experiment and simulation, we achieve unprecedented insights into the
      formation of Talbot images to be observed in transmission for light diffracted at
      wavelength-scale amplitude gratings. Emphasis is put on disclosing the impact and
      the interplay of various diffraction orders to the formation of Talbot images.
      They can be manipulated by selective filtering in the Fourier plane. Experiments
      are performed with a high-resolution interference microscope that measures the
      amplitude and phase of fields in real-space. Simulations have been performed
      using rigorous diffraction theory. Specific phase features, such as singularities
      found in the Talbot images, are discussed. This detailed analysis helps to
      understand the response of fine gratings. It provides moreover new insights into
      the fundamental properties of gratings that often find use in applications such
      as, e.g., lithography, sensing, and imaging.

PMID- 22418297
TI  - Correlation-based OTDR for in-service monitoring of 64-split TDM PON.
AB  - We demonstrate that the correlation-based optical time domain reflectometer
      (OTDR) can be used for the in-service monitoring of the 64-split time-division
      multiplexed passive optical network (TDM PON). To achieve this objective, we
      superimpose a pseudo noise (PN) sequence having a modulation depth of ~40% to the
      downstream signal and utilize it for the correlation detection. However, the use
      of such a large PN sequence can seriously deteriorate the performance of the
      downstream receiver. Thus, we apply 8B/10B encoding to the downstream signal, and
      then filter out the PN sequence at the downstream receiver by using a high-pass
      filter. As a result, the power penalty caused by the use of a large PN sequence
      is reduced to an acceptable level (<3 dB), while the dynamic range of this
      correlation-based OTDR is increased to ~30 dB. We then evaluate the performance
      of the proposed OTDR in the fiber link similar to the optical distribution
      network of the 64-split TDM PON. The results show that this OTDR can detect both
      the reflective and non-reflective events occurred in the feeder fiber as well as
      the reflective events in the drop fibers even in the 64-split TDM PON.

PMID- 22418298
TI  - Detection of elemental mercury by multimode diode laser correlation spectroscopy.
AB  - We demonstrate a method for elemental mercury detection based on correlation
      spectroscopy employing UV laser radiation generated by sum-frequency mixing of
      two visible multimode diode lasers. Resonance matching of the multimode UV laser
      is achieved in a wide wavelength range and with good tolerance for various
      operating conditions. Large mode-hops provide an off-resonance baseline,
      eliminating interferences from other gas species with broadband absorption. A
      sensitivity of 1 MUg/m3 is obtained for a 1-m path length and 30-s integration
      time. The performance of the system shows promise for mercury monitoring in
      industrial applications.

PMID- 22418299
TI  - Color rendering map: a graphical metric for assessment of illumination.
AB  - The method of evaluating color rendering using a visual, graphical metric is
      presented. A two-dimensional Color Rendering Map (CRM) of a light source's color
      rendering capabilities is explained and demonstrated. Extension of this technique
      to three-dimensional CRMs of objects under illumination is explained, including
      the method of introducing numerical indices in order to evaluate standards for
      specific applications in lighting. Three diverse applications, having a range
      from subtle to significant color variation, are shown with their respective CRMs.
      These three applications are also used to demonstrate how three differing light
      sources produce different maps. The results show a flexible, simple method to
      obtain a clear, visual determination of color rendering performance from
      differing sources used in differing illumination applications. The use of numeric
      indices in these applications shows how specific standards can be imposed in
      assessing the applicability of a light source.

PMID- 22418300
TI  - PSF shaping using adaptive optics for three-dimensional single-molecule super
      resolution imaging and tracking.
AB  - We present a novel approach for three-dimensional localization of single
      molecules using adaptive optics. A 52-actuator deformable mirror is used to both
      correct aberrations and induce two-dimensional astigmatism in the point-spread
      function. The dependence of the z-localization precision on the degree of
      astigmatism is discussed. We achieve a z-localization precision of 40 nm for
      fluorescent proteins and 20 nm for fluorescent dyes, over an axial depth of ~800
      nm. We illustrate the capabilities of our approach for three-dimensional high
      resolution microscopy with super-resolution images of actin filaments in fixed
      cells and single-molecule tracking of quantum-dot labeled transmembrane proteins
      in live HeLa cells.

PMID- 22418301
TI  - Low-cost ultra-thin broadband terahertz beam-splitter.
AB  - A low-cost terahertz beam-splitter is fabricated using ultra-thin LDPE plastic
      sheeting coated with a conducting silver layer. The beam splitting ratio is
      determined as a function of the thickness of the silver layer--thus any required
      splitting ratio can be printed on demand with a suitable rapid prototyping
      technology. The low-cost aspect is a consequence of the fact that ultra-thin LDPE
      sheeting is readily obtainable, known more commonly as domestic plastic wrap or
      cling wrap. The proposed beam-splitter has numerous advantages over float zone
      silicon wafers commonly used within the terahertz frequency range. These
      advantages include low-cost, ease of handling, ultra-thin thickness, and any
      required beam splitting ratio can be readily fabricated. Furthermore, as the beam
      splitter is ultra-thin, it presents low loss and does not suffer from Fabry-Perot
      effects. Measurements performed on manufactured prototypes with different
      splitting ratios demonstrate a good agreement with our theoretical model in both
      P and S polarizations, exhibiting nearly frequency-independent splitting ratios
      in the terahertz frequency range.

PMID- 22418302
TI  - Self-validating technique for the measurement of the linewidth enhancement factor
      in semiconductor lasers.
AB  - A new method for measuring the linewidth enhancement factor (alpha-parameter) of
      semiconductor lasers is proposed and discussed. The method itself provides an
      estimation of the measurement error, thus self-validating the entire procedure.
      The alpha-parameter is obtained from the temporal profile and the instantaneous
      frequency (chirp) of the pulses generated by gain switching. The time resolved
      chirp is measured with a polarization based optical differentiator. The accuracy
      of the obtained values of the alpha-parameter is estimated from the comparison
      between the directly measured pulse spectrum and the spectrum reconstructed from
      the chirp and the temporal profile of the pulse. The method is applied to a VCSEL
      and to a DFB laser emitting around 1550 nm at different temperatures, obtaining a
      measurement error lower than +/- 8%.

PMID- 22418303
TI  - Comparison of optical vortex detection methods for use with a Shack-Hartmann
      wavefront sensor.
AB  - In this paper we compare experimentally two methods of detecting optical vortices
      from Shack-Hartmann wavefront sensor (SHWFS) data, the vortex potential and the
      contour sum methods. The experimental setup uses a spatial light modulator (SLM)
      to generate turbulent fields with vortices. In the experiment, many fields are
      generated and detected by a SHWFS, and data is analysed by the two vortex
      detection methods. We conclude that the vortex potential method is more
      successful in locating vortices in these fields.

PMID- 22418305
TI  - Precision depth measurement of through silicon vias (TSVs) on 3D semiconductor
      packaging process.
AB  - We have proposed and demonstrated a novel method to measure depths of through
      silicon vias (TSVs) at high speed. TSVs are fine and deep holes fabricated in
      silicon wafers for 3D semiconductors; they are used for electrical connections
      between vertically stacked wafers. Because the high-aspect ratio hole of the TSV
      makes it difficult for light to reach the bottom surface, conventional optical
      methods using visible lights cannot determine the depth value. By adopting an
      optical comb of a femtosecond pulse laser in the infra-red range as a light
      source, the depths of TSVs having aspect ratio of about 7 were measured. This
      measurement was done at high speed based on spectral resolved interferometry. The
      proposed method is expected to be an alternative method for depth inspection of
      TSVs.

PMID- 22418304
TI  - Interference-free gas-phase thermometry at elevated pressure using hybrid
      femtosecond/picosecond rotational coherent anti-Stokes Raman scattering.
AB  - Rotational-level-dependent dephasing rates and nonresonant background can lead to
      significant uncertainties in coherent anti-Stokes Raman scattering (CARS)
      thermometry under high-pressure, low-temperature conditions if the gas
      composition is unknown. Hybrid femtosecond/picosecond rotational CARS is employed
      to minimize or eliminate the influence of collisions and nonresonant background
      for accurate, frequency-domain thermometry at elevated pressure. The ability to
      ignore these interferences and achieve thermometric errors of <5% is demonstrated
      for N2 and O2 at pressures up to 15 atm. Beyond 15 atm, the effects of collisions
      cannot be ignored but can be minimized using a short probe delay (~6.5 ps) after
      Raman excitation, thereby improving thermometric accuracy with a time- and
      frequency-resolved theoretical model.

PMID- 22418306
TI  - Proposal for a superconducting photon number resolving detector with large
      dynamic range.
AB  - We propose a novel photon number resolving detector structure with large dynamic
      range. It consists of the series connection of N superconducting nanowires, each
      connected in parallel to an integrated resistor. Photon absorption in a wire
      switches its current to the parallel resistor producing a voltage pulse and the
      sum of these voltages is measured at the output. The combination of this
      structure and a high input impedance preamplifier result in linear, high
      fidelity, and fast photon detection in the range from one to several tens of
      photons.

PMID- 22418307
TI  - Optimal Te-doping in GaSe for non-linear applications.
AB  - Centimeter-sized Te-doped GaSe ingots were grown from the charge compositions of
      GaSe with nominals 0.05, 0.1, 0.5, 1, and 3 mass% Te, which were identified as
      epsilon-GaSe:Te (0.01, 0.07, 0.38, 0.67, and 2.07 mass%) single crystals. The
      evolution of the absorption peaks of the phonon modes E'(2) (~ 0.584 THz) and
      E"(2) (1.77 THz) on Te-doping in GaSe:Te crystals was studied by THz time-domain
      spectroscopy. This study proposes that the evolution of both E'(2) and E''(2)
      absorption peaks correlates well with the optical quality of Te-doped GaSe
      crystals, which was confirmed by experimental results on the efficiency of THz
      generation by optical rectification. Maximal intensity of the absorption peak of
      the rigid layer mode E'(2) is proposed as a criterion for identification of
      optimal Te-doping in GaSe crystals.

PMID- 22418308
TI  - Pulsed operation of a high average power Yb:YAG thin-disk multipass amplifier.
AB  - An Yb:YAG thin-disk multipass laser amplifier system was developed operating in a
      10 Hz burst operation mode with 800 us burst duration and 100 kHz intra-burst
      repetition rate. Methods for the suppression of parasitic amplified spontaneous
      emission are presented. The average output pulse energy is up to 44.5 mJ and 820
      fs compressed pulse duration. The average power of 4.45 kW during the burst is
      the highest reported for this type of amplifier.

PMID- 22418309
TI  - Crosstalk calibration of multi-pixel photon counters using coherent states.
AB  - We present a novel method of calibration of crosstalk probability for multi-pixel
      photon counters (MPPCs) based on the measurement of the normalized second-order
      intensity correlation function of coherent light. The method was tested for
      several MPPCs, and was shown to be advantageous over the traditional calibration
      method based on the measurements of the dark noise statistics. The method can be
      applied without the need of modification for different kinds of spatially
      resolved single photon detectors.

PMID- 22418310
TI  - Detection of deep-subwavelength dielectric layers at terahertz frequencies using
      semiconductor plasmonic resonators.
AB  - Plasmonic bowtie antennas made of doped silicon can operate as plasmonic
      resonators at terahertz (THz) frequencies and provide large field enhancement
      close to their gap. We demonstrate both experimentally and theoretically that the
      field confinement close to the surface of the antenna enables the detection of
      ultrathin (100 nm) inorganic films, about 3750 times thinner than the free space
      wavelength. Based on model calculations, we conclude that the detection
      sensitivity and its variation with the thickness of the deposited layer are
      related to both the decay of the local THz field profile around the antenna and
      the local field enhancement in the gap of the bowtie antenna. This large field
      enhancement has the potential to improve the detection limits of plasmon-based
      biological and chemical sensors.

PMID- 22418311
TI  - Influence of the light trapping induced by surface plasmons and antireflection
      film in crystalline silicon solar cells.
AB  - In this paper, silicon solar cells with Ag nanoparticles deposited on a SiO2
      spacer were studied concentrating on the influence of the surface plasmon and the
      antireflection film. We experimentally found that the photocurrent conversion
      efficiency of the solar cell decorated by random arrays of self-assembled Ag
      nanoparticles increases firstly and decreases afterwards with increasing spacer
      thickness. Further investigations on the external quantum efficiency (EQE)
      illustrated this trend more clearly. It was also found that the effect of the
      surface plasmon on light absorption dominates over that of the antireflection
      film at the resonance wavelength which is an important factor determining the
      light trapping. Moreover, surface plasmon is determined by both the Si substrate
      and the SiO2 spacer. For self-assembled Ag particles on the surface of the solar
      cells in our experiments, appropriate spacer thickness (9-35 nm) could broaden
      the plasmon resonance, narrow the photocurrent suppression range, weaken the
      suppression amplitude and strengthen the gain at the resonance wavelength, while
      still providing antireflection effect.

PMID- 22418312
TI  - Detuned surface plasmon resonance scattering of gold nanorods for continuous wave
      multilayered optical recording and readout.
AB  - In a multilayered structure of absorptive optical recording media, continuous
      wave laser operation is highly disadvantageous due to heavy beam extinction. For
      a gold nanorod based recording medium, the narrow surface plasmon resonance (SPR)
      profile of gold nanorods enables the variation of extinction through mulilayers
      by a simple detuning of the readout wavelength from the SPR peak. The level of
      signal extinction through the layers can then be greatly reduced, resulting more
      efficient readout at deeper layers. The scattering signal strength may be
      decreased at the detuned wavelength, but balancing these two factors results an
      optimal scattering peak wavelength that is specific to each layer. In this paper,
      we propose to use detuned SPR scattering from gold nanorods as a new mechanism
      for continuous-wave readout scheme on gold nanorod based multilayered optical
      storage. Using this detuned scattering method, readout using continuous-wave
      laser is demonstrated on a 16 layer optical recording medium doped with heavily
      distributed, randomly oriented gold nanorods. Compared to SPR on-resonant
      readout, this method reduced the required readout power more than one order of
      magnitude, with only 60 nm detuning from SPR peak. The proposed method will be
      highly beneficial to multilayered optical storage applications as well as
      applications using a continuous medium doped heavily with plasmonic
      nanoparticles.

PMID- 22418313
TI  - Highly efficient Raman distributed feedback fibre lasers.
AB  - We demonstrate highly efficient Raman distributed feedback (DFB) fibre lasers for
      the first time with up to 1.6 W of continuous wave (CW) output power. The DFB
      Bragg gratings are written directly into two types of commercially available
      passive germano-silica fibres. Two lasers of 30 cm length are pumped with up to
      15 W of CW power at 1068 nm. The threshold power is ~2 W for a Raman-DFB (R-DFB)
      laser written in standard low-NA fibre, and only ~1 W for a laser written in a
      high-NA fibre, both of which oscillate in a narrow linewidth of <0.01 nm at ~1117
      nm and ~1109 nm, respectively. The slope efficiencies are ~74% and ~93% with
      respect to absorbed pump power in the low-NA fibre and high-NA fibre
      respectively. Such high conversion efficiency suggests that very little energy is
      lost in the form of heat through inefficient energy transfer. Our results are
      supported by numerical simulations, and furthermore open up for the possibility
      of having narrow linewidth all-fibre laser sources in wavelength bands not
      traditionally covered by rare-earth doped silica fibres. Simulations also imply
      that this technology has the potential to produce even shorter R-DFB laser
      devices at the centimetre-level and with mW-level thresholds, if Bragg gratings
      formed in fibre materials with higher intrinsic Raman gain coefficient than
      silica are used. These materials include for example tellurite or chalcogenide
      glasses. Using glasses like these would also open up the possibility of having
      narrow linewidth fibre sources with DFB laser oscillating much further into the
      IR than what currently is possible with rare-earth doped silica glasses.

PMID- 22418314
TI  - Conformal phosphor coating using capillary microchannel for controlling color
      deviation of phosphor-converted white light-emitting diodes.
AB  - We demonstrated a conformal phosphor coating method for phosphor-converted white
      light-emitting diodes (LEDs) using capillary microchannel formed by a fixture.
      The mixture of the phosphor particles and the silicone spontaneously flows in
      capillary microchannel and was pinned at the edge of the fixture due to the
      surface tension effect. The present coating method was applied to different
      packaging types with both the conventional chip and the vertical injection chip.
      Experimental results show this method can efficiently improve the angular color
      uniformity (ACU). Compared with those samples packaged by conventional dispensing
      coating, angular color correlated temperature (CCT) deviation of the test samples
      by the present method can reduce from 1500K to 200K for the average CCT 5200K
      from -90 degrees  to +90 view angles, and reduce from 5000K to 1000K for the
      average CCT 9150K. Additionally, this method can prevent the packaging non
      consistency that the average CCT varies from package to package due to the
      deviation of phosphor-silicone mixture volume. In the experiments, even when the
      phosphor-silicone mixture volume varies from 0.3 ul to 0.5 ul, the deviation of
      the average CCT is less than 80K.

PMID- 22418315
TI  - Electro-optical resonance modulation of vertical-cavity surface-emitting lasers.
AB  - Optical and electrical investigations of vertical-cavity surface-emitting lasers
      (VCSEL) with a monolithically integrated electro-optical modulator (EOM) allow
      for a detailed physical understanding of this complex compound cavity laser
      system. The EOM VCSEL light output is investigated to identify optimal working
      points. An electro-optic resonance feature triggered by the quantum confined
      Stark effect is used to modulate individual VCSEL modes by more than 20 dB with
      an extremely small EOM voltage change of less than 100 mV. Spectral mode analysis
      reveals modulation of higher order modes and very low wavelength chirp of < 0.5
      nm. Dynamic experiments and simulation predict an intrinsic bandwidth of the EOM
      VCSEL exceeding 50 GHz.

PMID- 22418316
TI  - Error analysis of a plane mirror interferometer based on geometric optical paths.
AB  - Plane mirror interferometer is a common way for the precision displacement
      measurement. However, during the measurement, it still suffers from disturbances
      such as misalignments, rotations and air refractive index fluctuations, which
      lead to poor accuracy. Traditional error analysis is rather limited in the static
      state and separation of the disturbances. In this paper, displacement measurement
      errors are analyzed, which are caused by the disturbed factors for a plane mirror
      interferometer. Then error modeling, which based on the geometric optical paths,
      is carried out by the partial differentiation theory. Moreover, the
      characteristics of the error are discussed by using this model. It is suggested
      that this model can release the measurement accuracy reduction brought by
      coupling effects between adjustment factor of the optical paths and the rotary
      error of the measured object (e. g. a guideway).

PMID- 22418317
TI  - Low-frequency Raman scattering of bioinspired self-assembled diphenylalanine
      nanotubes/microtubes.
AB  - Low-frequency Raman scattering from self-assembled bioinspired diphenylalanine
      (FF) nanotubes/microtubes (NTs/MTs) has been observed for the first time. Four
      double peaks are identified as the three-dimensional localized collective
      (acoustic phonon) vibrations of FF molecules in the subnanometer crystalline
      structure (biological building block) forming the FF NTs/MTs. The increased
      energy separations between two subpeaks caused by the loss of water in the
      nanochannel cores are due to the enhancement of vibrational couplings between the
      FF molecules as a result of the reduction of the influence from water on the
      coupling. The results provide experimental evidence of localized but still weakly
      coupled vibrations in organic crystalline nanostructures in the low-frequency
      region.

PMID- 22418318
TI  - Raman concentrators in Ge nanowires with dielectric coatings.
AB  - Raman spectroscopy is a powerful tool for investigating many fundamental
      properties of nanostructures, but extrinsic effects including background
      scattering and laser-induced heating can limit the analysis of intrinsic
      properties. A thin SiO2 dielectric coating is found to enhance the Raman signal
      from a single Ge nanowire by a factor of two as a result of wave interference.
      Consequently, the coated nanowire experiences less heating than a bare nanowire
      at equivalent signal intensities. The results demonstrate a simple and effective
      method to extend the limits of Raman analysis on single nanostructures and
      facilitate their characterization.

PMID- 22418319
TI  - Quantitative Cherenkov emission spectroscopy for tissue oxygenation assessment.
AB  - Measurements of Cherenkov emission in tissue during radiation therapy are shown
      to enable estimation of hemoglobin oxygen saturation non-invasively, through
      spectral fitting of the spontaneous emissions from the treated tissue. Tissue
      oxygenation plays a critical role in the efficacy of radiation therapy to kill
      tumor tissue. Yet in-vivo measurement of this has remained elusive in routine use
      because of the complexity of oxygen measurement techniques. There is a spectrally
      broad emission of Cherenkov light that is induced during the time of irradiation,
      and as this travels through tissue from the point of the radiation deposition,
      the tissue absorption and scatter impart spectral changes. These changes can be
      quantified by diffuse spectral fitting of the signal. Thus Cherenkov emission
      spectroscopy is demonstrated for the first time quantitatively in vitro and
      qualitatively in vivo, and has potential for real-time online tracking of tissue
      oxygen during radiation therapy when fully characterized and developed.

PMID- 22418320
TI  - Fast fabrication of nano-structured anti-reflection layers for enhancement of
      solar cells performance using plasma sputtering and infrared assisted roller
      embossing techniques.
AB  - This paper reports the continuous fabrication of dual-side nano-structured anti
      reflection protective layer for performance enhancement of solar cells using
      plasma sputtering and infrared assisted roller embossing techniques. Nano
      structures were first deposited onto the surface of glass substrates using the
      plasma sputtering technique. After electroforming, a nickel master mold
      containing nano-array of 30 nm was obtained. The mold was then attached to the
      surfaces of the two metallic rollers in an infrared assisted roll-to-roll
      embossing facility. The embossing facility was used to replicate the nano
      structures onto 60 MUm thick polyethylene terephthalate (PET) films in the
      experiments. The embossed films were characterized using UV-vis
      spectrophotometer, atomic force microscope (AFM), and scanning electron
      microscope (SEM); its total conversion efficiency for solar cells was also
      measured by a solar simulator. The experimental results showed that the
      fabricated films could effectively reduce the reflectance and increase the
      conversion efficiency of solar cells. The proposed method shows great potential
      for fast fabrication of the anti-reflection protective layer of solar cells due
      to its simplicity and versatility.

PMID- 22418321
TI  - Quality quantifier of indirect measurements.
AB  - A quality quantifier, referred to as measurement quality quantifier (MQQ), is
      proposed for indirect measurements. It satisfies the property that the MQQ of the
      data fusion of two or more independent measurements is the sum of the MQQs of the
      individual measurements and can also be determined in absolute terms for ill
      posed problems. It is calculated from the covariance and Jacobian matrices of the
      observations, but the same result is also obtained using the covariance and
      averaging kernel matrices of the retrieved quantities. In the case of
      measurements of a continuous distribution a quantifier that provides the
      information distribution can be derived from the MQQ. The proposed quantifiers
      are herewith used for the quality assessment of atmospheric ozone measurements
      performed by IASI and MIPAS instruments.

PMID- 22418322
TI  - Dispersion relation and radiation properties of plasmonic crystals with
      triangular lattices.
AB  - The optical properties of plasmonic crystals consisting of triangular lattices
      are theoretically investigated using rigorous coupled-wave analysis. Two types of
      structures were analyzed, one composed of an array of short cylindrical pillars
      on a flat metal surface and the other composed of an array of shallow cylindrical
      holes formed in a flat metal surface. The dispersion relations and radiation
      properties of the second and the third bands around the Gamma point in the first
      Brillouin zone were investigated. We found these properties to be highly
      dependent on the radii of the cylindrical pillars and holes relative to the
      lattice constant. We also examined the influence on the dispersion relations and
      radiation properties of the deviation of the cross-section of the pillars and
      holes from a perfect circle.

PMID- 22418323
TI  - High resolution wavefront correction with photocontrolled deformable mirror.
AB  - We demonstrate that a novel actuation scheme, employed in an optical control
      deformable mirror, can be more convenient than the conventional discrete fixed
      actuators approach. The Photo-Controlled Deformable Mirror (PCDM) mirror
      leverages consumer LCD display technology in the wavefront forming control,
      enabling flexible programmable configuration of the actuation geometry. This new
      approach simplifies the driving electronics, relaxing the per channel cost of
      high spatial control of the wavefront forming surface. In our experiment we
      tested the PCDM by applying the equivalent of 36, 76 and 201 actuators, this by
      just changing the light driving pattern. We demonstrated the effectiveness of
      this technique in a closed loop setup, which showed performances superior to the
      state of the art for similar DM, while providing a significant reduction in the
      hardware complexity.

PMID- 22418324
TI  - Spatiotemporal focusing through a thin scattering layer.
AB  - We analyze the spatiotemporal distortions of an ultrashort pulse focused through
      a thin scattering surface. We show and experimentally verify that in such a
      scenario temporal distortions are proportional to the distance from the optical
      axis and are present only outside the focal point, as result of geometrical path
      length differences. We use wavefront shaping to correct for the spatiotemporal
      distortions and to temporally compress chirped input pulses through the
      scattering medium.

PMID- 22418325
TI  - Generation of two attosecond pulses with tunable delay using orthogonally
      polarized chirped laser pulses.
AB  - We investigate theoretically the high-order harmonic generation (HHG) by two
      orthogonally-polarized linearly chirped laser pulses. We show that such
      generating field has a specific temporal variation of the ellipticity which
      provides generation of two XUV attosecond pulses with tunable delay between them.
      This delay is controlled by the delay between the two generating pulses.
      Perspectives of application of this technique for the attosecond pump -
      attosecond probe experiments are discussed.

PMID- 22418326
TI  - GaAs-based air-slot photonic crystal nanocavity for optomechanical oscillators.
AB  - We theoretically investigate an optomechanical structure consisting of two
      parallel GaAs membranes with an air-slot type photonic crystal nanocavity. The
      optical cavity has a quality factor of 4.8 * 10<sup>6</sup> at 1.52 MUm and an
      extremely small modal volume of 0.015 of a cubic wavelength for the fundamental
      mode in a vacuum. The localized electric field near the air/dielectric-object
      boundary provides a large optomechanical coupling factor of ~990 GHz/nm. The
      fundamental mechanical mode resonance is 95 MHz and a quality factor is 83,800 at
      room temperature, nearly seven times higher than that for a similar Si-based
      structure. This high mechanical quality factor of a GaAs-based structure stems
      from low thermoelastic loss and leads to more effective optical control of
      nanomechanical oscillators.

PMID- 22418328
TI  - Continuous-wave VECSEL Raman laser with tunable lime-yellow-orange output.
AB  - We report a compact CW KGW Raman laser with intracavity nonlinear mixing, pumped
      by the intracavity field of a VECSEL. By temperature tuning an intracavity LBO
      crystal, we obtained two separate tunable emissions bands, namely 548.5 - 566 nm
      for sum-frequency-generation (SFG) of the fundamental and Stokes wavelengths, and
      577.5 - 596 nm for second-harmonic-generation (SHG) of the Stokes wavelength. The
      maximum output powers for SFG and SHG were 0.8 W @ 560 nm and 0.52 W @ 592.5 nm,
      with corresponding diode-to-visible optical conversion efficiencies of 4.2% and
      2.9%. These preliminary results show strong potential for expanding the spectral
      coverage of VECSEL lasers.

PMID- 22418327
TI  - Hong-Ou-Mandel interference mediated by the magnetic plasmon waves in a three
      dimensional optical metamaterial.
AB  - We studied the quantum properties of magnetic plasmon waves in a three
      dimensional coupled metamaterial. A Hong-Ou-Mandel dip of two-photon interference
      with a visibility of 86 +/- 6.0% was explicitly observed, when the sample was
      inserted into one of the two arms of the interferometer. This meant that the
      quantum interference property survived in such a magnetic plasmon wave-mediated
      transmission process, thus testifying the magnetic plasmon waves owned a quantum
      nature. A full quantum model was utilized to describe our experimental results.
      The results showed that the metamaterials could not only steer the classical
      light but also the non-classical light and they might have potential application
      in the future quantum information.

PMID- 22418329
TI  - STED with wavelengths closer to the emission maximum.
AB  - In stimulated emission depletion (STED) nanoscopy the wavelength of the STED beam
      is usually tuned towards the red tail of the emission maximum of the fluorophore.
      Shifting the STED wavelength closer to the emission peak, i.e. towards the blue
      region, favorably increases the stimulated emission cross-section. However, this
      blue-shifting also increases the probability to excite fluorophores that have
      remained in their ground state, compromising the image contrast. Here we present
      a method to exploit the higher STED efficiency of blue-shifted STED beams while
      maintaining the contrast in the image. The method is exemplified by imaging
      immunolabeled features in mammalian cells with an up to 3-fold increased STED
      efficiency compared to that encountered in standard STED nanoscopy
      implementations.

PMID- 22418330
TI  - A stretch-tunable plasmonic structure with a polarization-dependent response.
AB  - We experimentally demonstrate a stretchable plasmonic structure composed of a
      monolayer array of gold semishells with dielectric cores on an elastic PDMS
      substrate. The composite structure is fabricated using simple and inexpensive
      self-assembly and transfer-printing techniques, and it supports Bragg-type
      surface plasmon resonances whose frequencies are sensitive to the arrangement of
      the metallic semishells. Under uniaxial stretching, the lattice symmetry of this
      plasmonic structure can be reconfigured from hexagonal to monoclinic, leading to
      resonance frequency shifts from 200 THz to 191 THz for the TM polarization and
      from 200 THz to 198 THz for the TE polarization with a strain up to 20%,
      respectively. Compared with previously reported tunable plasmonic structures, the
      reconfiguration of lattice symmetry offers a promising approach to tune the
      surface plasmon resonance with a polarization-dependent response at the standard
      telecommunication band, and such tunable plasmonic structure might be exploited
      in realizing photonic devices such as sensors, switches and filters.

PMID- 22418332
TI  - Broadband graphene electro-optic modulators with sub-wavelength thickness.
AB  - Graphene's featureless optical absorption, ultrahigh carrier mobility, and
      variable optical absorption by an applied gate voltage enable a new breed of
      optical modulators with broad optical and electrical bandwidths. Here we report
      on an electro-optic modulator that integrates single-layer graphene in a sub
      wavelength thick, reflective modulator structure. These modulators provide a
      large degree of design freedom, which allows tailoring of their optical
      properties to specific needs. Current devices feature an active aperture ~100 um,
      and provide uniform modulation with flat frequency response from 1 Hz to >100
      MHz. These novel, low insertion-loss graphene-based modulators offer solutions to
      a variety of high-speed amplitude modulation tasks that require optical amplitude
      modulation without phase distortions, a flat frequency response, or ultra-thin
      geometries, such as for controlling monolithic, high-repetition rate mode-locked
      lasers or active interferometers.

PMID- 22418331
TI  - Fluorescence correlation spectroscopy with a total internal reflection
      fluorescence STED microscope (TIRF-STED-FCS).
AB  - We characterize a novel fluorescence microscope which combines the high spatial
      discrimination of a total internal reflection epi-fluorescence (epi-TIRF)
      microscope with that of stimulated emission depletion (STED) nanoscopy. This
      combination of high axial confinement and dynamic-active lateral spatial
      discrimination of the detected fluorescence emission promises imaging and
      spectroscopy of the structure and function of cell membranes at the macro
      molecular scale. Following a full theoretical description of the sampling volume
      and the recording of images of fluorescent beads, we exemplify the performance
      and limitations of the TIRF-STED nanoscope with particular attention to the
      polarization state of the laser excitation light. We demonstrate fluorescence
      correlation spectroscopy (FCS) with the TIRF-STED nanoscope by observing the
      diffusion of dye molecules in aqueous solutions and of fluorescent lipid analogs
      in supported lipid bilayers in the presence of background signal. The nanoscope
      reduced the out-of-focus background signal. A lateral resolution down to 40-50 nm
      was attained which was ultimately limited by the low lateral signal-to-background
      ratio inherent to the confocal epi-TIRF scheme. Together with the estimated axial
      confinement of about 55 nm, our TIRF-STED nanoscope achieved an almost isotropic
      and less than 1 attoliter small all-optically induced measurement volume.

PMID- 22418333
TI  - A simple delay-line 4-PPM demodulator with near-optimum performance.
AB  - We describe a simple 4-PPM demodulator that uses analog delay lines and simple 1
      bit comparators to determine the least-significant bit and most-significant bit
      of the 4-PPM encoded data without additional digital signal processing. We show
      that with good optical filtering the comparator-based demodulator can
      theoretically operate with sensitivity only 0.23 dB from the optimum 4-ary
      receiver. We describe as an example of this approach the demodulator built for
      the Lunar Laser Communication Demonstration and show measured performance within
      1.1 dB of the expected sensitivity. The technique is extendable to higher-order,
      and higher-symbol-rate orthogonal modulation formats.

PMID- 22418334
TI  - Dispersion control in square lattice photonic crystal fiber using hollow ring
      defects.
AB  - We propose a new dispersion control scheme by introducing hollow ring defects
      having a central air hole and a GeO2-or F-doped silica ring with in a square
      lattice photonic crystal fiber. We confirmed the flexible dispersion
      controllability in the proposed structure in two aspects of dispersion
      managements: ultra-flattened near-zero dispersion in the 530 nm-bandwidth over
      all communication bands and dispersion compensation in C, L, and U band with a
      high compensation ratio of 0.96~1.0 in reference to the standard single mode
      fiber. The proposed SLPCFs were also estimated to have an inherently low splice
      loss due to the index contrast between the doped-ring and silica that kept a good
      guidance even along with collapsed air holes, which cannot be achieved in
      conventional PCFs.

PMID- 22418335
TI  - Characterization of semiconductor-laser phase noise and estimation of bit-error
      rate performance with low-speed offline digital coherent receivers.
AB  - We develop a systematic method for characterizing semiconductor-laser phase
      noise, using a low-speed offline digital coherent receiver. The field spectrum,
      the FM-noise spectrum, and the phase-error variance measured with such a receiver
      can completely describe phase-noise characteristics of lasers under test. The
      sampling rate of the digital coherent receiver should be much higher than the
      phase-fluctuation speed. However, 1 GS/s is large enough for most of the single
      mode semiconductor lasers. In addition to such phase-noise characterization,
      interpolating the taken data at 1.25 GS/s to form a data stream at 10 GS/s, we
      can predict the bit-error rate (BER) performance of multi-level modulated optical
      signals at 10 Gsymbol/s. The BER degradation due to the phase noise is well
      explained by the result of the phase-noise measurements.

PMID- 22418336
TI  - Compact camera module testing equipment with a conversion lens.
AB  - Modified testing equipment for adjusting the back focal length of a compact
      camera module (CCM) is proposed. The advantages of this modified testing
      equipment which includes a conversion lens are that it saves on testing space,
      offers a smaller sized testing chart, as well as high speed chart changing, and
      variable object distances. The modified testing equipment can produce a test
      chart of 38.32 mm compared to an equivalent testing chart of 5000 mm with the
      conventional testing equipment. At the regular object distance of 2000 mm, both
      total track and testing chart size for the modified test equipment were 8.3% that
      of the conventional testing equipment. By using this testing equipment, the
      testing space can be shrunk significantly.

PMID- 22418338
TI  - TEM 00 mode content of a two stage single-frequency Yb-doped PCF MOPA with 246 W
      of output power.
AB  - Gravitational wave detectors require linearly polarized single-frequency laser
      sources with a high fractional TEM 00 mode content. We investigated the modal
      decomposition of a polarization maintaining photonic crystal fiber with a mode
      field diameter of 29 um, operating in a single-frequency master-oscillator power
      amplifier scheme, with respect to the TEM nm modes. Low degradation of the beam
      quality with increasing pump power could be observed, while a maximum power in
      the TEM 00 mode of 203 W was achieved.

PMID- 22418337
TI  - 175 fs Tm:Lu2O3 laser at 2.07 um mode-locked using single-walled carbon
      nanotubes.
AB  - Single-walled carbon nanotube saturable absorbers were designed and fabricated
      for passive mode-locking of bulk lasers operating in the 2 MUm spectral range.
      Mode-locked lasers based on Tm:Lu2O3 single crystals containing different Tm3+
      doping concentrations were studied. Nearly transform-limited pulses as short as
      175 fs at 2070 nm were generated at 88 MHz repetition rate.

PMID- 22418339
TI  - Photophoretic trapping of absorbing particles in air and measurement of their
      single-particle Raman spectra.
AB  - A new method is demonstrated for optically trapping micron-sized absorbing
      particles in air and obtaining their single-particle Raman spectra. A 488-nm
      Gaussian beam from an Argon ion laser is transformed by conical lenses (axicons)
      and other optics into two counter-propagating hollow beams, which are then
      focused tightly to form hollow conical beams near the trapping region. The
      combination of the two coaxial conical beams, with focal points shifted relative
      to each other along the axis of the beams, generates a low-light-intensity
      biconical region totally enclosed by the high-intensity light at the surface of
      the bicone, which is a type of bottle beam. Particles within this region are
      trapped by the photophoretic forces that push particles toward the low-intensity
      center of this region. Raman spectra from individual trapped particles made from
      carbon nanotubes are measured. This trapping technique could lead to the
      development of an on-line real-time single-particle Raman spectrometer for
      characterization of absorbing aerosol particles.

PMID- 22418340
TI  - Cavity-assisted emission of polarization-entangled photons from biexcitons in
      quantum dots with fine-structure splitting.
AB  - We study the quantum properties and statistics of photons emitted by a quantum
      dot biexciton inside a cavity. In the biexciton-exciton cascade, fine-structure
      splitting between exciton levels degrades polarization-entanglement for the
      emitted pair of photons. However, here we show that the polarization-entanglement
      can be preserved in such a system through simultaneous emission of two degenerate
      photons into cavity modes tuned to half the biexciton energy. Based on detailed
      theoretical calculations for realistic quantum-dot and cavity parameters, we
      quantify the degree of achievable entanglement.

PMID- 22418342
TI  - Label-free bacteria detection using evanescent mode of a suspended core terahertz
      fiber.
AB  - We propose for the first time an E. coli bacteria sensor based on the evanescent
      field of the fundamental mode of a suspended-core terahertz fiber. The sensor is
      capable of E. coli detection at concentrations in the range of 10(4)-10(9)
      cfu/ml. The polyethylene fiber features a 150 um core suspended by three deeply
      sub-wavelength bridges in the center of a 5.1 mm-diameter cladding tube. The
      fiber core is biofunctionalized with T4 bacteriophages which bind and eventually
      destroy (lyse) their bacterial target. Using environmental SEM we demonstrate
      that E. coli is first captured by the phages on the fiber surface. After 25
      minutes, most of the bacteria is infected by phages and then destroyed with ~1
      MUm-size fragments remaining bound to the fiber surface. The bacteria-binding and
      subsequent lysis unambiguously correlate with a strong increase of the fiber
      absorption. This signal allows the detection and quantification of bacteria
      concentration. Presented bacteria detection method is label-free and it does not
      rely on the presence of any bacterial "fingerprint" features in the THz spectrum.

PMID- 22418343
TI  - Color rendition engine.
AB  - A source of white light with continuously tuned color rendition properties, such
      as color fidelity, as well as color saturating and color dulling ability has been
      developed. The source, which is composed of red (R), amber (A), green (G), and
      blue (B) light-emitting diodes, has a spectral power distribution varied as a
      weighted sum of "white" RGB and AGB blends. At the RGB and AGB end-points, the
      source has a highest color saturating and color dulling ability, respectively, as
      follows from the statistical analysis of the color-shift vectors for 1269 Munsell
      samples. The variation of the weight parameter allows for continuously traversing
      all possible metameric RAGB blends, including that with the highest color
      fidelity. The source was used in a psychophysical experiment on the estimation of
      the color appearance of familiar objects, such as vegetables, fruits, and soft
      drink cans of common brands, at correlated color temperatures of 3000 K, 4500 K,
      and 6500 K. By continuously tuning the weight parameter, each of 100 subjects
      selected RAGB blends that, to their opinion, matched lighting characterized as
      "most saturating," "most dulling," "most natural," and "preferential". The end
      point RGB and AGB blends have been almost unambiguously attributed to "most
      saturating" and "most dulling" lighting, respectively. RAGB blends that render a
      highest number of colors with high fidelity have, on average, been attributed to
      "most natural" lighting. The "preferential" color quality of lighting has, on
      average, been matched to RAGB blends that provide color rendition with fidelity
      somewhat reduced in favor of a higher saturation. Our results infer that tunable
      "color rendition engines" can validate color rendition metrics and provide
      lighting meeting specific needs and preferences to color quality.

PMID- 22418344
TI  - Gabor fusion technique in a Talbot bands optical coherence tomography system.
AB  - In this paper we show how to advantageously combine two effects to enhance the
      sensitivity with depth in Fourier domain (FD) optical coherence tomography (OCT):
      Talbot bands (TB) and Gabor-based fusion (GF) technique. TB operation is achieved
      by routing the two beams, from the object arm and from the reference arm in the
      OCT interferometer, along parallel separate paths towards the spectrometer. By
      adjusting the lateral gap between the two beams in their way towards the
      spectrometer, the position for the maximum of contrast variation of spectral
      modulation versus the optical path difference in the interferometer is adjusted.
      For five values of the focus position, the gap between the two beams is
      readjusted to reach maximum sensitivity. Then, similar to the procedure employed
      in the GF technique, a compound image is formed by stitching together the parts
      of the five images that exhibited maximum brightness. The smaller the diameters
      of the two beams, the narrower the visibility profile versus depth in Talbot
      bands, which brings advantages in terms of mirror terms attenuation. However,
      this leads to a larger spot on the linear camera, which introduces losses,
      therefore the combined procedure, TB/GF is investigated for four different values
      of the beam diameters of the two beams. Future cameras with larger pixel size may
      take full advantage of the TB/GF procedure proposed here.

PMID- 22418345
TI  - Liquid crystal gratings based on alternate TN and PA photoalignment.
AB  - A diffraction grating is proposed by periodically defining the liquid-crystal
      director distribution to form alternate parallel aligned and twist nematic
      regions in a cell placed between two crossed polarizers. Based on the combined
      phase and amplitude modulation, both 1D and 2D tunable gratings are demonstrated.
      Low voltage ON/OFF switching of 1st order diffracted light with extinction ratio
      over 80 is achieved within a small voltage interval of 0.15 Vrms. Unique four
      state feature of the cell is obtained and their applications in optical logic
      devices are discussed.

PMID- 22418346
TI  - Azimuthally polarized laser mode generation by multilayer mirror with wideband
      grating-induced TM leakage in the TE stopband.
AB  - A new intracavity laser polarization-mode selection scheme relying upon a TE/TM
      diffractive dichroism principle in a grating multilayer mirror is proposed and
      demonstrated. The grating diffracts the first orders between the TE and TM band
      edges of the angular spectra of the laser mirror inducing a leakage of the TM
      polarization into the mirror substrate through the multilayer stack whereas TE
      diffraction into the substrate is forbidden. This mechanism is non-resonant, thus
      relatively wide-band. Applied with a circular-line grating in the 1.0 um - 1.1 um
      wavelength range, this mirror filters out the radially polarization mode and
      causes the emission of the azimuthally polarized mode. An original amorphous
      silicon grating technology was developed and the optical function demonstrated in
      a Nd:YAG laser.

PMID- 22418347
TI  - A microfiber coupler tip thermometer.
AB  - A compact thermometer based on a broadband microfiber coupler tip is
      demonstrated. This sensor can measure a broad temperature interval ranging from
      room temperature to 1283  degrees C with sub-200 um spatial resolution. An
      average sensitivity of 11.96 pm/ degrees C was achieved for a coupler tip with
      ~2.5 um diameter. This is the highest temperature measured with a silica optical
      fiber device.

PMID- 22418348
TI  - Multiple visible emissions by means of up-conversion process in a microstructured
      tellurite glass optical fiber.
AB  - We present a microstructured fiber whose 9 um diameter core consists in three
      concentric rings made of three active glasses having different rare earth oxide
      dopants, Yb3+/Er3+, Yb3+/Tm3+ and Yb3+/Pr3+, respectively. Morphological and
      optical characterization of the optical fiber are presented. The
      photoluminescence spectrum is investigated for different pumping conditions using
      a commercial 980 nm laser diode. Tuning of the RGB (or white light) emission is
      demonstrated not only by adjusting the pump power but also by using an optical
      iris as spatial filter which, thanks to the microstructured core, also acts as a
      spectral filter.

PMID- 22418349
TI  - Generalized ellipsometry in-situ quantification of organic adsorbate attachment
      within slanted columnar thin films.
AB  - We apply generalized ellipsometry, well-known to be sensitive to the optical
      properties of anisotropic materials, to determine the amount of fibronectin
      protein that adsorbs onto a Ti slanted columnar thin film from solution. We find
      that the anisotropic optical properties of the thin film change upon organic
      adsorption. An optical model for ellipsometry data analysis incorporates an
      anisotropic Bruggeman effective medium approximation. We find that differences in
      experimental data from before and after fibronectin adsorption can be solely
      attributable to the uptake of fibronectin within the slanted columnar thin film.
      Simultaneous, in-situ generalized ellipsometry and quartz crystal microbalance
      measurements show excellent agreement on the amount and rate of fibronectin
      adsorption. Quantitative characterization of organic materials within three
      dimensional, optically anisotropic slanted columnar thin films could permit their
      use in optical sensor applications.

PMID- 22418351
TI  - Enhanced compression rate of integral images by using motion-compensated residual
      images in three-dimensional integral-imaging.
AB  - In this paper, we proposed a new approach to notably enhance the compression rate
      of integral images by using the motion-compensated residual images (MCRIs). In
      the proposed method, sub-images (SIs) transformed from the picked-up elemental
      images of a three-dimensional (3-D) object, are sequentially rearranged with a
      spiral scanning topology. The moving vectors among the SIs, then, are estimated
      and compensated with the block-matching algorithm. Furthermore, spatial
      redundancy among the SIs is also removed by computing the differences between the
      local SIs and their motion-compensated versions, from which a sequence of MCRIs
      are finally generated and compressed with the MPEG-4 algorithm. Experimental
      results show that the compression efficiency of the proposed method has been
      improved up to 861.1% on average from that of the JPEG-based elemental images
      (EIs) method, and up to 1,497.0% and 118.8% on average from those of the MPEG
      based MCSIs and the MPEG-based RIs method, respectively.

PMID- 22418350
TI  - Gold nanoparticles on the surface of soda-lime glass: morphological, linear and
      nonlinear optical characterization.
AB  - Materials presenting high optical nonlinearity, such as materials containing
      metal nanoparticles (NPs), can be used in various applications in photonics. This
      motivated the research presented in this paper, where morphological, linear and
      nonlinear optical characteristics of gold NPs on the surface of bulk soda-lime
      glass substrates were investigated as a function of nanoparticle height. The NPs
      were obtained by annealing gold (Au) thin films previously deposited on the
      substrates. Pixel intensity histogram fitting on Atomic Force Microscopy (AFM)
      images was performed to obtain the thickness of the deposited film. Image
      analysis was employed to obtain the statistical distribution of the average
      height of the NPs. In addition, absorbance spectra of the samples before and
      after annealing were measured. Finally, the nonlinear refractive index (n2) and
      the nonlinear absorption index (alpha2) at 800 nm were obtained before and after
      annealing by using the thermally managed eclipse Z-scan (TM-EZ) technique with a
      Ti:Sapphire laser (150 fs pulses). Results show that both n2 and alpha2 at this
      wavelength change signs after the annealing and that the samples presented a high
      nonlinear refractive index.

PMID- 22418352
TI  - All-optical diffractive/transmissive switch based on coupled cycloidal
      diffractive waveplates.
AB  - Pairs of cycloidal diffractive waveplates can be used to doubly diffract or
      collinearly propagate laser radiation of the appropriate wavelength. The use of a
      dynamic phase retarder placed in between the pair can be utilized to switch
      between the two optical states. We present results from the implementation of an
      azo-based retarder whose optical properties can be modulated using light itself.
      We show fast and efficient switching between the two states for both CW and
      single nanosecond laser pulses of green radiation. Contrasts greater than 100:1
      were achieved. The temporal response as a function of light intensity is
      presented and the optical switching is shown to be polarization independent.

PMID- 22418353
TI  - Quantitative single-shot imaging of complex objects using phase retrieval with a
      designed periphery.
AB  - Measuring transmission and optical thickness of an object with a single intensity
      recording is desired in many fields of imaging research. One possibility to
      achieve this is to employ phase retrieval algorithms. We propose a method to
      significantly improve the performance of such algorithms in optical imaging. The
      method relies on introducing a specially designed phase object into the specimen
      plane during the image recording, which serves as a constraint in the subsequent
      phase retrieval algorithm. This leads to faster algorithm convergence and
      improved final accuracy. Quantitative imaging can be performed by a single
      recording of the resulting diffraction pattern in the camera plane, without using
      lenses or other optical elements. The method allows effective suppression of the
      "twin-image", an artefact that appears when holograms are read out. Results from
      numerical simulations and experiments confirm a high accuracy which can be
      comparable to that of phase-stepping interferometry.

PMID- 22418354
TI  - 3-dimensional eigenmodal analysis of plasmonic nanostructures.
AB  - We introduce a 3-dimensional electromagnetic eigenmodal algorithm for the
      theoretical analysis of resonating nano-optical structures. The method, a variant
      of the Jacobi-Davidson algorithm, solves the electric field vector wave, or curl
      curl, equation for the electromagnetic eigenmodes of resonant optical structures
      with a finite element method. In particular, the method includes transparent
      boundary conditions that enable the analysis of resonating structures in
      unbounded space. We demonstrate the performance of the method. First, we
      calculate the modes of several dielectric resonator antennas and compare them to
      theoretically determined results. Second, we calculate the modes of a nano-cuboid
      and compare them to theoretically determined results. Third, we numerically
      analyze spherical nanoparticles and compare the result to the theoretical Mie
      solution. Fourth, we analyze optical dipole antenna configurations in order to
      assess the method's capability for solving technologically relevant problems.

PMID- 22418355
TI  - Eu3+ reduction and efficient light emission in Eu2O3 films deposited on Si
      substrates.
AB  - A stable Eu3+ -> Eu2+ reduction is accomplished by thermal annealing in N2
      ambient of Eu2O3 films deposited by magnetron sputtering on Si substrates.
      Transmission electron microscopy and x-ray diffraction measurements demonstrate
      the occurrence of a complex reactivity at the Eu2O3/Si interface, leading to the
      formation of Eu2+ silicates, characterized by a very strong (the measured
      external quantum efficiency is about 10%) and broad room temperature
      photoluminescence (PL) peak centered at 590 nm. This signal is much more
      efficient than the Eu3+ emission, mainly consisting of a sharp PL peak at 622 nm,
      observed in O2-annealed films, where the presence of a SiO2 layer at the Eu2O3/Si
      interface prevents Eu2+ formation.

PMID- 22418356
TI  - Entangled photon generation in two-period quasi-phase-matched parametric down
      conversion.
AB  - We proposed and demonstrated a simple but deterministic scheme for generating
      polarization-entangled photon pairs at telecommunication wavelengths with type-II
      quasi-phase-matched spontaneous parametric down-conversion (QPM-SPDC) having two
      poling periods. We fabricated a LiNbO3 crystal having two poling periods so as to
      generate entangled photons at two wavelengths, i.e., 1506 nm and 1594 nm. We
      characterized the two-photon polarization state with state tomography and
      confirmed that the state was highly entangled.

PMID- 22418357
TI  - Silicon photodiodes with high photoconductive gain at room temperature.
AB  - Silicon photodiodes with high photoconductive gain are demonstrated. The
      photodiodes are fabricated in a complementary metal-oxide-semiconductor (CMOS)
      compatible process. The typical room temperature responsivity at 940 nm is >20
      A/W and the dark current density is ~ 100 nA/cm2 at 5 V reverse bias, yielding a
      detectivity of ~ 10(14) Jones. These photodiodes are good candidates for
      applications that require high detection sensitivity and low bias operation.

PMID- 22418358
TI  - Picosecond pulse generation in a hybrid Q-switched laser source by using a
      microelectromechanical mirror.
AB  - We present a novel Q-switched laser source using a micro-optical
      electromechanical mirror (MOEM) designed for short pulse emission. It is based on
      a hybrid configuration including a passively Q-switched microchip laser coupled
      to a fiber cavity closed by a cantilever type MOEM acting as an active modulator.
      This specially designed mirror with a single reflecting gold membrane is switched
      by low bias voltage ~50 V (peak to peak). This device emits pulses at tunable
      repetition rates up to 1.6 kHz, with ~564 ps duration and 3.4 kW peak power,
      which constitutes the shortest pulse duration ever reported with MOEMs based
      pulsed lasers.

PMID- 22418359
TI  - Room temperature polariton lasing vs. photon lasing in a ZnO-based hybrid
      microcavity.
AB  - We report on the room temperature polariton lasing and photon lasing in a ZnO
      based hybrid microcavity under optical pumping. A series of experimental studies
      of the polariton lasing (exciton-photon detunings of delta = -119 meV) in the
      strong-coupling regime are discussed and compared to a photon lasing (delta = -45
      meV) in the weak-coupling regime obtained in the same structure. The measured
      threshold power density (31.8 kW/cm2) of polariton lasing is one order of
      magnitude lower than that of the photon lasing (318.2 kW/cm2). In addition, the
      comparison between polariton lasing and photon lasing is done in terms of the
      linewidth broadening, blue-shift of the emission peak, and polarization.

PMID- 22418360
TI  - Efficient frequency shifting of dispersive waves at solitons.
AB  - We demonstrate frequency redshifting and blueshifting of dispersive waves at
      group velocity horizons of solitons in fibers. The tunnelling probability of
      waves that cannot propagate through the fiber-optical solitons (horizons) is
      measured and described analytically. For shifts up to two times the soliton
      spectral width, the waves frequency shift with probability exceeding 90% rather
      than tunnelling through the soliton in our experiment. We also discuss key
      features of fiber optical Cherenkov radiation such as high efficiency and large
      bandwidth within this framework.

PMID- 22418361
TI  - Complementary computer generated holography for aesthetic watermarking.
AB  - We present herein an original solution for the watermarking of holograms in
      binary graphic arts without unaesthetic diffractive effect. It is based on the
      Babinet principle of complementary diffractive structures adapted to Lohmann-type
      computer generated holograms. We introduce the concept and demonstrate its
      interest for anti-counterfeiting applications with the decoding of a hidden data
      matrix. A process of thermal lithography is used for the manufacturing of binary
      graphic arts containing complementary computer generated holograms.

PMID- 22418362
TI  - Active stabilization for optically synchronized optical parametric chirped pulse
      amplification.
AB  - The development of new high power laser sources tends toward optical parametric
      chirped pulse amplification (OPCPA) in recent years. One of the difficulties in
      OPCPA is the the temporal overlap between pump and seed pulses. In this work we
      characterize our timing jitter on a single-shot basis using spectrally resolved
      cross-correlation in combination with a position sensitive detector. A commercial
      beam stabilization is adapted to actively enhance temporal overlap. This delay
      stabilizer reduces the RMS jitter from sigma = 127 fs down to sigma = 24 fs. The
      enhanced temporal overlap is demonstrated in our frontend and we propose the
      scheme to be applicable in many optically synchronized high-repetition-rate OPCPA
      systems.

PMID- 22418363
TI  - Spatially resolved modal spectroscopy of Er:Yb doped multifilament-core fiber
      amplifier.
AB  - The spatially resolved spectral (S2) imaging method is applied on an active
      microstructured fiber, with a multi-filament core (MFC). This type of fiber has
      been designed to be the last amplifying stage of a source for a long range
      coherent lidar. Studying the influence of the bending radius on the modal content
      with or without gain, we demonstrate that an upper-bound of the high-order modes
      content can be found by performing the S2 imaging on the bleached fiber. S2
      imaging is then used to verify that the output beam of the MFC fiber can be made
      effectively single-mode. We also show that it can be simply adapted for measuring
      the fiber birefringence. Finally, a comparison of the MFC fiber mode area with
      that of a standard large mode area Erbium doped step index fiber illustrates the
      interest of the MFC structure for high power amplifiers.

PMID- 22418364
TI  - Analytic design method for optimal imaging: coupling three ray sets using two
      free-form lens profiles.
AB  - In this work, a new two-dimensional optics design method is proposed that enables
      the coupling of three ray sets with two lens surfaces. The method is especially
      important for optical systems designed for wide field of view and with clearly
      separated optical surfaces. Fermat's principle is used to deduce a set of
      functional differential equations fully describing the entire optical system. The
      presented general analytic solution makes it possible to calculate the lens
      profiles. Ray tracing results for calculated 15th order Taylor polynomials
      describing the lens profiles demonstrate excellent imaging performance and the
      versatility of this new analytic design method.

PMID- 22418365
TI  - Pulse propagation through a slab with time-periodic dielectric function
      epsilon(t).
AB  - We describe pulse propagation through a slab with periodic dielectric function
      epsilon(t), thus extending our previous investigation for monochromatic incidence
      [Phys. Rev. A 79, 053821 (2009)]. Based on the concepts of phase and group
      delays, we prove that, for an incident quasi-monochromatic pulse, the transmitted
      pulse can be expressed as a superposition of partial pulses that are exact
      replicas of the incident pulse and that exit the slab with a time delay. These
      partial pulses have harmonic carrier frequencies omega c - nOmega (n is an
      integer, omega c is the carrier frequency of the incident pulse, and Omega =
      2pi/T is the slab modulation frequency). We find numerically that these partial
      pulses can be fast (peak velocity vn > c or vn < 0) or slow (vn << c). Further,
      we investigate the peak velocity v p of the outcoming pulse for several cases. We
      find that this peak velocity v p and the partial peak velocities vn do not
      diverge--as occurs to the group velocity v g of the bulk dynamic-periodic medium
      when omega c = Omega/2. We expect that these results could be verified in the
      microwave regime [see Halevi et al., Proc. SPIE 8095, 80950I (2011)].

PMID- 22418366
TI  - Improving high-order harmonic yield using wavefront-controlled ultrashort laser
      pulses.
AB  - In this work we show that it is possible to increase the high-order harmonic
      yield when using wavefront-shaped laser beams. The investigation of the beam
      profile near the interaction region shows that the optimized beam is asymmetric
      and has a larger diameter. Thus, the optimized beam leads to a higher yield even
      if the peak intensity is lower compared to an unoptimized beam. This indicates
      that the wavefront of the fundamental laser beam and, accordingly, the focal
      profile play an important role in the efficient generation of high-order harmonic
      radiation.

PMID- 22418367
TI  - Waveguides in three-dimensional photonic bandgap materials for particle
      accelerator on a chip architectures.
AB  - The quest for less costly and more compact high-energy particle accelerators
      makes research on alternative acceleration mechanisms an important enterprise.
      From the multitude of suggested concepts, the photonic accelerator design by B.
      M. Cowan [Phys. Rev. ST Accel. Beams 11, 011301 (2008)] stands out by its
      distinct potential of creating an accelerator on a chip [Proposal E-163, SLAC
      (2001)]. Herein, electrons are accelerated by the axial electric field of a
      strongly confined optical mode of an air waveguide within a silicon-based three
      dimensional photonic band-gap material. Using a combination of direct laser
      writing and silicon double inversion, we here present the first experimental
      realization of this complex structure. Optical spectroscopy provides unambiguous
      evidence for the existence of an accelerating waveguide mode with axial
      polarization.

PMID- 22418368
TI  - 3D displacement measurements of the tympanic membrane with digital holographic
      interferometry.
AB  - A digital holographic interferometry (DHI) system with three object-illumination
      beams is used for the first time to measure micro-deformations along the x, y and
      z axes (3D) on the tympanic membrane (TM) surface of a post-mortem cat. In order
      to completely and accurately measure the TM surface displacements its shape is
      required to map on it the x, y and z micro-deformations. The surface contour is
      obtained by applying small shifts to the object illumination source position. A
      cw laser in stroboscopic mode and a CCD camera were used and synchronized to the
      acoustic excitation wave that produces a resonant vibration mode on the tympanic
      membrane surface. This research work reports on the 3D full field of view
      response of the TM to sound pressure, and has as its main goal the presentation
      of DHI as an alternative technique to study the TM real displacement behavior
      when subjected to sound waves, so it can be used as a diagnostic tool to prevent
      and treat TM diseases.

PMID- 22418369
TI  - Detectivity enhancement in quantum well infrared photodetectors utilizing a
      photonic crystal slab resonator.
AB  - We characterize the performance of a quantum well infrared photodetector (QWIP),
      which is fabricated as a photonic crystal slab (PCS) resonator. The strongest
      resonance of the PCS is designed to coincide with the absorption peak frequency
      at 7.6 um of the QWIP. To accurately characterize the detector performance, it is
      illuminated by using single mode mid-infrared lasers. The strong resonant
      absorption enhancement yields a detectivity increase of up to 20 times. This
      enhancement is a combined effect of increased responsivity and noise current
      reduction. With increasing temperature, we observe a red shift of the PCS-QWIP
      resonance peak of -0.055 cm(-1)/K. We attribute this effect to a refractive index
      change and present a model based on the revised plane wave method.

PMID- 22418370
TI  - Dynamic and high-resolution live cell imaging by direct electron beam excitation.
AB  - We propose a direct electron-beam excitation assisted optical microscope with a
      resolution of a few tens of nanometers and it can be applied for observation of
      dynamic movements of nanoparticles in liquid. The technique is also useful for
      live cell imaging under physiological conditions as well as observation of
      colloidal solution, microcrystal growth in solutions, etc. In the microscope,
      fluorescent materials are directly excited with a focused electron beam. The
      direct excitation with an electron beam yields high spatial resolution since the
      electron beam can be focused to a few tens of nanometers in the specimens. In
      order to demonstrate the potential of our proposed microscope, we observed the
      movements of fluorescent nanoparticles, which can be used for labelling
      specimens, in a water-based solution. We also demonstrated an observation result
      of living CHO cells.

PMID- 22418371
TI  - Effect of annealing treatment on electroluminescence from GaN/Si
      nanoheterostructure array.
AB  - A GaN/Si nanoheterostructure array was prepared by growing GaN nanostructures on
      silicon nanoporous pillar array (Si-NPA). Based on as-grown and annealed GaN/Si
      NPA, two light-emitting diodes (LEDs) were fabricated. It was found that after
      the annealing treatment, both the turn-on voltage and the leakage current density
      of the nanoheterostructure varied greatly, together with the electroluminescence
      (EL) changed from a yellow band to a near infrared band. The EL variation was
      attributed to the radiative transition being transformed from a defect-related
      recombination in GaN to an interfacial recombination of GaN/Si-NPA. Ours might
      have provided an effective approach for fabricating GaN/Si-based LEDs with
      different emission wavelengths.

PMID- 22418372
TI  - Orthogonally polarized dual-wavelength Nd:LuVO4 laser at 1086 nm and 1089 nm.
AB  - A comparison between the fluorescence spectra of the Nd-doped vanadate crystals
      (Nd:YVO4, Nd:GdVO4, Nd:LuVO4) for the 4F3/2 -> 4I11/2 transition is studied. We
      numerically analyze the condition of gain-to-loss balance via an uncoated
      intracavity etalon to achieve the dual-wavelength operation. We further
      experimentally demonstrate the orthogonally polarized dual-wavelength laser with
      a single Nd:LuVO4 crystal. The simultaneous dual-wavelength Nd:LuVO4 laser at
      1085.7 nm in sigma polarization and 1088.5 nm in pi polarization is realized. At
      an incident pump power of 12 W, the average output power obtained at 1085.7 nm
      and 1088.5 nm is 0.4 W and 1.7 W, respectively.

PMID- 22418373
TI  - Graphene-filled hollow optical fiber saturable absorber for efficient soliton
      fiber laser mode-locking.
AB  - We demonstrate a novel in-line saturable absorber based on hollow optical fiber
      (HOF) filled with graphene composite for high power operation of mode-locked
      fiber laser. Evanescent field of guided mode propagating in few centimeter-long
      HOF interacts with the graphene/polyvinyl acetate (PVAc) composite, which enables
      robust and efficient nonlinear absorption leading to stable passive mode-locking.
      The mode-locked fiber laser generates soliton pulses with 5.9-nm spectral
      bandwidth and its maximum output power is measured up to 80 mW. We also observe
      passive harmonic mode-locking of soliton laser delivering stable pulses with a
      repetition rate of 506.9 MHz at 33rd harmonics.

PMID- 22418374
TI  - Absolute distance measurement with micrometer accuracy using a Michelson
      interferometer and the iterative synthetic wavelength principle.
AB  - We present a novel system that can measure absolute distances of up to 300 mm
      with an uncertainty of the order of one micrometer, within a timeframe of 40
      seconds. The proposed system uses a Michelson interferometer, a tunable laser, a
      wavelength meter and a computer for analysis. The principle of synthetic wave
      creation is used in a novel way in that the system employs an initial low
      precision estimate of the distance, obtained using a triangulation, or time-of
      flight, laser system, or similar, and then iterates through a sequence of
      progressively smaller synthetic wavelengths until it reaches micrometer
      uncertainties in the determination of the distance. A further novel feature of
      the system is its use of Fourier transform phase analysis techniques to achieve
      sub-wavelength accuracy. This method has the major advantages of being relatively
      simple to realize, offering demonstrated high relative precisions better than 5 *
      10(-5). Finally, the fact that this device does not require a continuous line-of
      sight to the target as is the case with other configurations offers significant
      advantages.

PMID- 22418375
TI  - 2 um femtosecond fiber laser at low repetition rate and high pulse energy.
AB  - In the paper, a 2 um high energy fs fiber laser is presented based on Tm doped
      fiber at a low repetition rate. The seed laser was designed to generate pulse
      train at 2 um at a pulse repetition rate of 2.5 MHz. The low repetition rate seed
      oscillator eliminated extra devices such as AO pulse picker. Two-stage fiber
      amplifier was used to boost pulse energy to 0.65 uJ with chirped pulse
      amplification.

PMID- 22418376
TI  - Laser-induced periodic structures for light extraction efficiency enhancement of
      GaN-based light emitting diodes.
AB  - The laser-induced periodic surface structure technique was used to form
      simultaneously dual-scale rough structures (DSRS) with spiral-shaped nanoscale
      structure inside semi-spherical microscale holes on p-GaN surface to improve the
      light-extraction efficiency of light-emitting diodes (LEDs). The light output
      power of DSRS-LEDs was 30% higher than that of conventional LEDs at an injection
      current of 20 mA. The enhancement in the light output power could be attributed
      to the increase in the probability of photons to escape from the increased
      surface area of textured p-GaN surface.

PMID- 22418377
TI  - Plasmonic V-groove waveguides with Bragg grating filters via nanoimprint
      lithography.
AB  - We demonstrate spectral filtering with state-of-the-art Bragg gratings in
      plasmonic V-groove waveguides fabricated by wafer scale processing based on
      nanoimprint lithography. Transmission spectra of the devices having 16 grating
      periods exhibit spectral rejection of the channel plasmon polaritons with 8.2 dB
      extinction ratio and -3 dB bandwidth of Deltalambda = 39.9 nm near
      telecommunications wavelengths. Near-field scanning optical microscopy
      measurements verify spectral reflection from the grating structures, and the
      oscillations of propagating modes along grating-less V-grooves correspond well
      with effective refractive index values calculated by finite element simulations
      in COMSOL. The results represent advancement towards the implementation of
      plasmonic V-grooves with greater functional complexity and mass-production
      compatibility.

PMID- 22418378
TI  - Simplification of millimeter-wave radio-over-fiber system employing heterodyning
      of uncorrelated optical carriers and self-homodyning of RF signal at the
      receiver.
AB  - A simplified millimeter-wave (mm-wave) radio-over-fiber (RoF) system employing a
      combination of optical heterodyning in signal generation and radio frequency (RF)
      self-homodyning in data recovery process is proposed and demonstrated. Three
      variants of the system are considered in which two independent uncorrelated
      lasers with a frequency offset equal to the desired mm-wave carrier frequency are
      used to generate the transmitted signal. Uncorrelated phase noise in the
      resulting mm-wave signal after photodetection was overcome by using RF self
      homodyning in the data recovery process. Theoretical analyses followed by
      experimental results and simulated characterizations confirm the system's
      performance. A key advantage of the system is that it avoids the need for high
      speed electro-optic and electronic devices operating at the RF carrier frequency
      at both the central station and base stations.

PMID- 22418379
TI  - High-performance monolithically integrated 120 degrees  downconverter with
      relaxed hardware constraints.
AB  - A coherent receiver based on a 120 degrees  downconverter architecture, inherited
      from previous approaches at the microwave and optical fields, is proposed,
      analyzed, numerically evaluated and compared to the conventional 90 degrees 
      downconverter alternative. It is shown that, due to its superior calibration
      procedure, the new downconverter architecture allows full compensation of the
      imbalances in its optical front-end thus leading to an extended dynamic range and
      a broader operating bandwidth than its 90 degrees  counterpart. Simulation
      results from monolithically integrated downconverters show that our approach can
      be an interesting alternative to support efficient modulation schemes such as M
      QAM that is being studied as potential candidate for the next generation of
      optical communication systems.

PMID- 22418380
TI  - Distributed mode filtering rod fiber amplifier delivering 292W with improved mode
      stability.
AB  - We demonstrate a high power fiber (85 MUm core) amplifier delivering up to 292
      Watts of average output power using a mode-locked 30 ps source at 1032 nm.
      Utilizing a single mode distributed mode filter bandgap rod fiber, we demonstrate
      44% power improvement before the threshold-like onset of mode instabilities by
      operating the rod fiber in a leaky waveguide regime. We investigate the guiding
      dynamics of the rod fiber and report a distinct bandgap blue-shifting as function
      of increased signal power level. Furthermore, we theoretically analyze the
      guiding dynamics of the DMF rod fiber and explain the bandgap blue-shifting with
      thermally induced refractive index change of the refractive index profile.

PMID- 22418381
TI  - A bright point source of ultrashort hard x-ray pulses using biological cells.
AB  - We demonstrate that the interaction of intense femtosecond light on a plain solid
      substrate can be substantially altered by a few micron layer coating of bacterial
      cells, live or dead. Using E. Coli cells, we show that at an intensity of 10(16)W
      cm(-2), the bremsstraahlung hard x-ray emission (up to 300 keV), is increased by
      more than two orders of magnitude as compared to a plain glass slab. Particle-in
      cell simulations carried out by modeling the bacterial cells as ellipsoidal
      particles show that the hot electron generation is indeed enhanced by the
      presence of microstructures. This new methodology should pave way for using
      microbiological systems of varied shapes to control intense laser produced
      plasmas for EUV/x-ray generation.

PMID- 22418382
TI  - Data detection algorithms for multiplexed quantum dot encoding.
AB  - A group of quantum dots can be designed to have a unique spectral emission by
      varying the size of the quantum dots (wavelength) and number of quantum dots
      (intensity). This technique has been previously proposed for biological tags and
      object identification. The potential of this system lies in the ability to have a
      large number of distinguishable wavelengths and intensity levels. This paper
      presents a communications system model for MxQDs including the interference
      between neighbouring QD colours and detector noise. An analytical model of the
      signal-to-noise ratio of a Charge-Coupled Device (CCD) spectrometer is presented
      and confirmed with experimental results. We then apply a communications system
      perspective and propose data detection algorithms that increase the readability
      of the quantum dots tags. It is demonstrated that multiplexed quantum dot
      barcodes can be read with 99.7% accuracy using the proposed data detection
      algorithms in a system with 6 colours and 6 intensity values resulting in 46,655
      unique spectral codes.

PMID- 22418383
TI  - A simple route to fabricate artificial compound eye structures.
AB  - A biologically inspired compound-eye structure, which composes of ~5,867
      honeycomb-patterned microlenses, was fabricated on a hemispherical shell. The
      fabrication process was simple and low-cost, which involves a femtosecond laser
      enhanced wet etching and casting process followed by a thermomechanical process
      to convert the film into a hemispherical surface. By optimizing the parameters of
      thermomechanical process to form the curvilinear surface, the experimental result
      shows that the microlenses are omnidirectionally aligned on the dome with lens
      diameters of ~85 um and the angle between two lens of ~2 degrees , and the
      individual microlenses have rudimentary focusing and imaging properties. The
      artificial compound-eye structure fabricated by this method has great potential
      applications in scale-invariant processing, robot vision, and fast motion
      detection.

PMID- 22418384
TI  - Numerical approximation for Brillouin fiber ring resonator.
AB  - A new method for describing the Stimulated Brillouin Scattering (SBS) generated
      in a fiber ring resonator in dynamic regime is presented. Neglecting the time
      derivatives of the fields amplitudes, our modeling method describes the lasers
      steady-state operations as well as their transient characteristics or pulsed
      emission. The developed approach has shown a very good agreement between the
      theoretical predictions given by the SBS model and the experimental results.

PMID- 22418385
TI  - Numerical and experimental studies of coupling-induced phase shift in resonator
      and interferometric integrated optics devices.
AB  - Coupling induced effects are higher order effects inherent in waveguide
      evanescent coupling that are known to spectrally distort optical performances of
      integrated optics devices formed by coupled resonators. We present both numerical
      and experimental studies of coupling-induced phase shift in various basic
      integrated optics devices. Rigorous finite difference time domain simulations and
      systematic experimental characterizations of different basic structures were
      conducted for more accurate parameter extraction, where it can be observed that
      coupling induced wave vector may change sign at the increasing gap separation.
      The devices characterized in this work were fabricated by CMOS-process 193 nm
      Deep UV (DUV) lithography in silicon-on-insulator (SOI) technology.

PMID- 22418386
TI  - Photoacoustic microscopy achieved by microcavity synchronous parallel acquisition
      technique.
AB  - We report on a sub-cellular resolution photoacoustic microscopy (PAM) system that
      employs microcavity synchronous parallel acquisition technique for detecting the
      weak photoacoustic (PA) signal excited by a modulated continuous wave (CW) laser
      source. The gas microcavity transducer is developed based on the fact that the
      bulk modulus of the gas is far less than the solid and the change of the air-gas
      pressure is inversely proportional to the gas volume, making it extremely
      sensitive to the tiny PA pressure wave. Besides, considering PA wave expends in
      various directions, detecting PA signals from different position and adding them
      together can increase the detecting sensitivity and the signal to noise
      ratio(SNR), then we employs two microphone to acquire PA wave synchronously and
      parallelly. We show that the developed PAM system is capable of label-free
      imaging and differentiating of the hemoglobin distribution within single red
      blood cells under normal and anemia conditions.

PMID- 22418387
TI  - Storage and retrieval of ghost images in hot atomic vapor.
AB  - Ghost imaging is an imaging technique in which the image of an object is revealed
      only in the correlation measurement between two beams of light, whereas the
      individual measurements contain no imaging information. Here, we experimentally
      demonstrate storage and retrieval of ghost images in hot atomic rubidium vapor.
      Since ghost imaging requires (quantum or classical) multimode spatial correlation
      between two beams of light, our experiment shows that the spatially multimode
      correlation, a second-order correlation property of light, can indeed be
      preserved during the storage-retrieval process. Our work, thus, opens up new
      possibilities for quantum and classical two-photon imaging, all-optical image
      processing, and quantum communication.

PMID- 22418388
TI  - Autoimmunity: innovation in pathogenesis and therapy.

PMID- 22418389
TI  - T-cell receptor signaling and the pathogenesis of autoimmune arthritis: insights
      from mouse and man.
AB  - The immune system has evolved to survey and respond appropriately to the universe
      of foreign pathogens, while at the same time deploying an intricate repertoire of
      mechanisms that keep responses to host tissues in check. For the adaptive immune
      system, specificity and sensitivity are provided by a large repertoire of antigen
      T-cell receptors (TCRs) constructed in their extracellular domain to recognize
      antigenic peptide fragments restricted and presented by histocompatibility
      complex molecules, and coupled through intracellular domains to signal
      transduction modules that serve to transmit environmental cues inside the cell.
      In this review we consider recent evidence that has provided insight into how
      altered TCR signaling thresholds could contribute to human autoimmune arthritis,
      including rheumatoid arthritis (RA), and the spondyloarthropathies (SpA). We also
      discuss mechanistic studies that demonstrate how perturbations of T-cell antigen
      receptor signaling in the SKG mouse model can promote systemic autoimmunity and
      the intersection with essential innate immune pathways that lead to the
      development of chronic inflammatory phenotypes.

PMID- 22418390
TI  - [Single port laparoscopic biliopancreatic bypass without gastrectomy].

PMID- 22418391
TI  - [Damage control surgery in non-traumatic abdominal emergencies].

PMID- 22418392
TI  - Enhanced thermoelectric power in nanopatterned carbon nanotube film.
AB  - Despite the small or near-zero Seebeck coefficient of metallic nanotubes, a
      nanotube film can be readily scaled up in length. Thus so can its thermoelectric
      power. In this work, we inserted a nanomesh pattern into a carbon nanotube film
      by using an anodized aluminum oxide membrane as an etching mask. We found that by
      patterning densely packed nanoscale holes into the nanotube film, its total
      thermoelectric power can be further increased, by as much as 30% (from 29 to 39
      MUV K(-1)). We present this finding, attributed to electron localization due to
      nanopatterning, as indicative of the potential of a new degree of freedom.

PMID- 22418393
TI  - Human anterior prefrontal cortex encodes the 'what' and 'when' of future
      intentions.
AB  - On a daily basis we form numerous intentions to perform specific actions.
      However, we often have to delay the execution of intended actions while engaging
      in other demanding activities. Previous research has shown that patterns of
      activity in human prefrontal cortex (PFC) can reveal our current intentions.
      However, two fundamental questions have remained unresolved: (a) how does the PFC
      encode information about future tasks while we are busy engaging in other
      activities, and (b) how does the PFC enable us to commence a stored task at the
      intended time? Here we investigate how the brain stores and retrieves future
      intentions during occupied delays, i.e. while a person is busy performing a
      different task. For this purpose, we conducted a neuroimaging study with a time
      based prospective memory paradigm. Using multivariate pattern classification and
      fMRI we show that during an occupied delay, activity patterns in the anterior PFC
      encode the content of 'what' subjects intend to do next, and 'when' they intend
      to do it. Importantly, distinct anterior PFC regions store the 'what' and 'when'
      components of future intentions during occupied maintenance and self-initiated
      retrieval. These results show a role for anterior PFC activity patterns in
      storing future action plans and ensuring their timely retrieval.

PMID- 22418394
TI  - Task-related BOLD responses and resting-state functional connectivity during
      physiological clamping of end-tidal CO(2).
AB  - Carbon dioxide (CO(2)), a potent vasodilator, is known to have a significant
      impact on the blood-oxygen level dependent (BOLD) signal. With the growing
      interest in studying synchronized BOLD fluctuations during the resting state, the
      extent to which the apparent synchrony is due to variations in the end-tidal
      pressure of CO(2) (PETCO(2)) is an important consideration. CO(2)-related
      fluctuations in BOLD signal may also represent a potential confound when studying
      task-related responses, especially if breathing depth and rate are affected by
      the task. While previous studies of the above issues have explored retrospective
      correction of BOLD fluctuations related to arterial PCO(2), here we demonstrate
      an alternative approach based on physiological clamping of the arterial CO(2)
      level to a near-constant value. We present data comparing resting-state
      functional connectivity within the default-mode-network (DMN), as well as task
      related BOLD responses, acquired in two conditions in each subject: 1) while
      subject's PETCO(2) was allowed to vary spontaneously; and 2) while controlling
      subject's PETCO(2) within a narrow range. Strong task-related responses and areas
      of maximal signal correlation in the DMN were not significantly altered by
      suppressing fluctuations in PETCO(2). Controlling PETCO(2) did, however, improve
      the performance of retrospective physiological noise correction techniques,
      allowing detection of additional regions of task-related response and resting
      state connectivity in highly vascularized regions such as occipital cortex. While
      these results serve to further rule out systemic physiological fluctuations as a
      significant source of apparent resting-state network connectivity, they also
      demonstrate that fluctuations in arterial CO(2) are one of the factors limiting
      sensitivity in task-based and resting-state fMRI, particularly in regions of high
      vascular density. This must be considered when comparing subject groups who might
      exhibit differences in respiratory physiology or breathing patterns.

PMID- 22418396
TI  - Diffusion tensor imaging tractography of the fornix and belief confidence in
      first-episode psychosis.
AB  - Previous studies have demonstrated that patients with psychosis are more
      confident in beliefs and judgments compared to healthy participants and
      psychiatric controls with major depression. A recent study conducted by our
      research group has provided evidence for hippocampal pathology in association
      with overconfidence in a first-episode psychosis sample. The fornix is the
      primary efferent neural pathway of the hippocampus and may also play a role in
      self-certainty pathophysiology. The current investigation applied diffusion
      tensor imaging tractography to a first-episode psychosis sample to explore
      whether integrity of the fornix is associated with self-certainty. High
      resolution structural magnetic resonance and diffusion tensor images were
      obtained in 44 people with a first-episode psychosis. Diffusion tensor imaging
      tractography was used to estimate fractional anisotrophy (FA), a measure of white
      matter integrity, in the fornix. Confidence in beliefs and judgments was measured
      with the self-certainty subscale of the Beck Cognitive Insight Scale (BCIS). The
      analysis showed that self-certainty significantly correlated to FA values in the
      right fornix but was nonsignificant for the left fornix. The findings indicate
      anatomical dysconnectivity of the right fornix in correlation with BCIS-rated
      self-certainty in our first-episode psychosis sample. When considered with our
      previously published self-certainty-hippocampus result in a first-episode
      psychosis sample, overlapping with that of this study, the results indicate a
      concurrence of volumetric reductions in hippocampus and fornix pathology in
      correlation with self-certainty.

PMID- 22418395
TI  - Association between schizophrenia and genetic variation in DCC: a case-control
      study.
AB  - Schizophrenia is a highly heritable neurodevelopmental disorder associated with
      alterations in synaptic connectivity. Deleted in colorectal cancer (DCC), a
      receptor for the guidance cue netrin-1, plays a pivotal role in organizing
      neuronal circuitry by guiding growing axons and dendrites to their correct
      targets and by influencing synaptic connectivity. Results from experiments we
      previously conducted in dcc-heterozygous mice show that DCC plays a critical role
      in the developmental organization of the mesocorticolimbic dopamine (DA)
      circuitry. Furthermore we have shown that reduced expression of DCC during
      development and/or throughout life confers resilience to the development of
      schizophrenia-like DA and behavioural abnormalities. Importantly, this
      "protective" phenotype only emerges after puberty. Here we assess whether DCC may
      contribute to the risk of schizophrenia. We examined single nucleotide
      polymorphisms (SNPs) located in the DCC gene for association with schizophrenia
      using a case-control sample consisting of 556 unrelated schizophrenic patients
      and 208 healthy controls. We found one SNP, rs2270954, to be nominally associated
      with schizophrenia; patients were less likely to be heterozygous at this locus
      and more likely to be homozygous for the minor allele (chi(2)=9.84, df=2, nominal
      p=0.0071). Intriguingly, this SNP is located within the 3' untranslated region,
      an area known to contain a number of regulatory sequences that determine the
      stability and translation efficacy of mRNA. These results, together with our
      previous findings from studies in rodents, point at DCC as a promising novel
      candidate gene that may contribute to the genetic basis behind individual
      differences in susceptibility to schizophrenia.

PMID- 22418397
TI  - Aspects of countertransference.

PMID- 22418399
TI  - Synthetic cannabinoid use:  recognition and management.
AB  - In the past few years, synthetic cannabinoid products have been increasingly used
      by adolescents and young adults. These products are marketed as herbal or
      aromatic incense and potpourri, but their psychoactive properties appear to be
      due to the addition of synthetic cannabinoids. When smoked, they can produce
      significant psychoactive and physical effects similar to cannabis. Changes in
      cognition, behavioral disturbances, alterations in mood, and perceptual changes
      have been reported. An emerging body of literature indicates that use of these
      products is associated with anxiety and other negative mood changes not typical
      of cannabis intoxication. Use of synthetic cannabinoid products has been
      associated with new onset psychosis or exacerbation of pre-existing psychosis,
      although current evidence cannot establish a definitive link between synthetic
      cannabinoids and psychosis. Clinicians should suspect synthetic cannabinoid
      product use if a patient: 1) presents with signs and symptoms consistent with
      cannabis use, 2) has negative routine urine toxicology screens, 3) is in a
      situation in which his or her urine is being routinely monitored for illicit
      substance use, and/or 4) presents with otherwise unexplained sudden onset
      psychosis. To make the diagnosis, clinicians should become familiar with the
      effects of synthetic cannabinoid use and have a high index of suspicion.

PMID- 22418398
TI  - The psychiatric cultural formulation:  translating medical anthropology into
      clinical practice.
AB  - This article reviews proposed revisions to the DSM-IV Outline for Cultural
      Formulation for clinical practice. The author begins by exploring the theoretical
      development of and assumptions involved in the Cultural Formulation. A case
      presentation is then used to demonstrate shortcomings in the current
      implementation of the Cultural Formulation based on older definitions of culture.
      Finally, the author recommends practical questions based on the growing
      anthropological literature concerning the interpersonal elements of culture and
      the social course of illness. A simple clear format that clinically translates
      social science concepts has the potential to increase use of the Cultural
      Formulation by all psychiatrists, not just those specializing in cultural
      psychiatry.

PMID- 22418400
TI  - Psychiatrists' emotional reactions to patient suicidal behavior.
AB  - BACKGROUND: Psychopathology is a risk factor for suicidal behavior. It is likely
      that psychiatrists will have to deal with an attempted or completed suicide by a
      patient at some point in their careers. The goal of this study was to assess
      psychiatrists' emotional reactions to patients' suicidal behavior. METHODS: Data
      were collected using a questionnaire that was administered to psychiatrists after
      a completed or attempted suicide by one of their patients. RESULTS: Thirty-four
      psychiatrists participated in the study and reported on 62 attempted suicides and
      11 completed suicides. All of the participants reported at least one emotion
      following the event. After an attempted suicide, trainees were more likely than
      consultants to experience psychological pain, guilt, self-doubt, and frustration.
      Being a trainee was also associated with psychological pain, guilt, fear, self
      doubt, and frustration in regression analysis. Shock, disbelief, fear, self
      doubt, and embarrassment were associated with completed rather than attempted
      suicides. CONCLUSIONS: Attempted and completed suicides have a significant impact
      on psychiatrists. The impact of an attempted suicide is usually less severe. The
      patterns of reaction differ between consultant and trainee psychiatrists.

PMID- 22418401
TI  - Medical countertransference and the trainee:  identifying a training gap.
AB  - OBJECTIVE: Although consultation-liaison (CL) psychiatrists are implicitly
      expected to recognize and consider interpersonal dynamics in clinical settings
      when offering recommendations, few guiding principles have been established,
      strongly suggesting the presence of a training gap. METHODS: Trainees in
      psychiatry residency programs accredited by the Accreditation Council for
      Graduate Medical Education (ACGME) were invited to complete an Internet-based, 20
      item, Likert scale questionnaire assessing practices and opinions concerning
      countertransference management and training. RESULTS: Of 192 respondents, 162
      (84%) reported having participated in a rotation on the CL service for at least
      some period of time and were eligible to complete the survey; 136 (71%) reported
      having completed at least 2 months of CL rotations. Approximately 80% identified
      a frequent need to address countertransference reactions when working with
      primary medical/surgical teams, but less than a quarter reported doing so
      regularly. The motivation for addressing such issues in over half of the
      respondents was the belief that it would be "clinically beneficial" to patients,
      although 40% of respondents also feared that this practice could "worsen the
      relationship between the CL consultant and the primary team." Regarding training,
      95% of respondents felt didactics addressing counter-transference would be
      "clinically beneficial"; however, three fifths of the respondents reported that
      "very few" to none of their didactics explored this issue. CONCLUSIONS: Results
      of this study suggest that discrepancies exist between trainee perceptions of the
      utility of countertransference management in CL psychiatry and actual training in
      this area. The authors discuss possible explanations for these discrepancies and
      advocate for the establishment of formal guidelines in training CL residents in
      such aptitudes. (Journal of Psychiatric Practice 2012;18:109-117).

PMID- 22418402
TI  - How biomarkers will change psychiatry: from clinical trials to practice. Part I:
      introduction.
AB  - Part I of this series defines biomarkers and discusses their research utility and
      potential application in clinical practice. To provide a frame of reference,
      biomarkers commonly used in general medicine are reviewed, with a focus on low
      density lipoprotein as a biomarker for risk of developing atherosclerosis. The
      use of biomarkers in research on psychiatric illnesses is then reviewed. While
      biomarkers currently have only a limited role in psychiatric care, their use has
      improved our ability to assess potential efficacy and safety of investigational
      new drugs. For example, positron emission tomography can be used to measure
      dopamine D2 receptor occupancy (relevant for antipsychotic effects) or serotonin
      transporter occupancy (relevant for antidepressant effects), to establish whether
      an agent reaches and to what extent it affects a specific target in the brain. In
      the future, biomarkers are likely to become an integral component of psychiatric
      treatment, providing information concerning a patient's odds of developing an
      illness, diagnosis, severity of illness, and level of response to therapeutic
      interventions. The second part of this series will discuss research on
      derivatives of the inflammatory biomarker thromboxane and depression.

PMID- 22418403
TI  - Doing forensic work, I:  starting the case.
AB  - The private forensic work discussed here is performed as an "expert" or "expert
      witness," defined in law as a person who is allowed to offer opinions to a court.
      One should not be an expert in forensic matters that involve one's own patients.
      Initial communication with the potential retaining entity (e.g., lawyer, court,
      agency, insurance company) should clarify the case, the lack of conflict of
      interest, one's possible forensic role, and practicalities such as fees,
      scheduling, and the way in which the work will be performed. One should guard
      against being misused, or having one's opinions misconstrued, in forensic
      matters, including being named as an expert witness without actually being
      retained (a "phantom expert"). Communicating orally with the retaining entity
      about progress and findings is important; written findings or opinions should be
      created or communicated only if the lawyer (or other retaining entity) requests
      them. Opinions should not be rendered without adequate review of complete and
      credible records and/or other sources, and even then caveats or disclaimers may
      be ethically or legally required. The forensic work routine almost always begins
      with record review, and may or may not include examining a litigant or other
      person.

PMID- 22418404
TI  - Hyperprolactinemia in a patient with a pituitary adenoma receiving antipsychotic
      drug therapy.
AB  - Hyperprolactinemia is a common consequence of treatment with an antipsychotic
      medication. It can result in hypogonadism due to the inhibitory effect of
      elevated prolactin levels on the hypothalamic-pituitary-gonadal hormonal axis. We
      present a case of hypogonadism secondary to hyperprolactinemia in a patient
      taking antipsychotic medication, with radiological evidence of a pituitary
      microadenoma. The relevance and investigation of hyperprolactinemia in patients
      being treated with antipsychotic medications are discussed.

PMID- 22418405
TI  - Safety considerations for outpatient electroconvulsive therapy.
AB  - As electroconvulsive therapy (ECT) requires general anesthesia and is associated
      with both cognitive and non-cognitive side effects, careful consideration must be
      given to the safety aspects of providing ECT on an outpatient basis. Drawing upon
      published literature and their clinical experience administering outpatient ECT,
      the authors propose best practices for safely providing ECT to outpatients. They
      review criteria for selecting patients for outpatient ECT as well as treatment
      and programmatic issues. The authors highlight the importance of educating
      referring clinicians as well as patients and their families about factors
      involved in the safe delivery of ECT for outpatients. Fiscal considerations and
      the drive toward reduced length of stay are prompting insurers and caregivers to
      choose outpatient over inpatient ECT. For each patient, such a choice merits a
      careful analysis of the risks of outpatient ECT, as well as the implementation of
      measures to ensure patient safety.

PMID- 22418406
TI  - Case against psychoanalysis in modern mental health services was unsubstantiated
      rhetoric.

PMID- 22418407
TI  - Health professionals can benefit from psychoanalysis.

PMID- 22418408
TI  - Psychoanalysis helps doctors understand patients.

PMID- 22418409
TI  - At least 25% with a mental health problem is a conservative estimate.

PMID- 22418410
TI  - Motorway safety is not a major public health problem.

PMID- 22418411
TI  - Health benefits matter, not tax revenue.

PMID- 22418412
TI  - MRHA works hard to ensure that medical devices work and are safe.

PMID- 22418413
TI  - Hormone replacement therapy provides no overall benefit on quality of life.

PMID- 22418414
TI  - Sports and exercise doctors: the unsung heroes of champions.

PMID- 22418416
TI  - The exaggerated claims of the mental health industry.

PMID- 22418417
TI  - Why no mention of private sector in appraisal of GP led commissioning?

PMID- 22418418
TI  - Psychoanalytical psychotherapy is distinct from psychoanalysis.

PMID- 22418421
TI  - Are nurses better than doctors?

PMID- 22418422
TI  - NHS "reform" in England: where is the public interest?

PMID- 22418423
TI  - Boundaries.

PMID- 22418424
TI  - Deaths from smoking: the avoidable holocaust.

PMID- 22418425
TI  - A new electronic theory of life (1925).

PMID- 22418426
TI  - Little evidence that one type of pain relief for labour is better than another,
      finds Cochrane review.

PMID- 22418427
TI  - Study confirms metal-on-metal hips are more likely to fail than other devices.

PMID- 22418428
TI  - Branches of the abdominal aorta.

PMID- 22418429
TI  - Tolerance of Mycorrhiza infected pistachio (Pistacia vera L.) seedling to drought
      stress under glasshouse conditions.
AB  - The influence of Glomus etunicatum colonization on plant growth and drought
      tolerance of 3-month-old Pistacia vera seedlings in potted culture was studied in
      two different water treatments. The arbuscular mycorrhiza (AM) inoculation and
      plant growth (including plant shoot and root weight, leaf area, and total
      chlorophyll) were higher for well-watered than for water-stressed plants. The
      growth of AM-treated seedlings was higher than non-AM-treatment regardless of
      water status. P, K, Zn and Cu contents in AM-treated shoots were greater than
      those in non-AM shoots under well-watered conditions and drought stress. N and Ca
      content were higher under drought stress, while AM symbiosis did not affect the
      Mg content. The contents of soluble sugars, proteins, flavonoid and proline were
      higher in mycorrhizal than non-mycorrhizal-treated plants under the whole water
      regime. AM colonization increased the activities of peroxidase enzyme in
      treatments, but did not affect the catalase activity in shoots and roots under
      well-watered conditions and drought stress. We conclude that AM colonization
      improved the drought tolerance of P. vera seedlings by increasing the
      accumulation of osmotic adjustment compounds, nutritional and antioxidant enzyme
      activity. It appears that AM formation enhanced the drought tolerance of
      pistachio plants, which increased host biomass and plant growth.

PMID- 22418430
TI  - Influence of glutathione chemical effectors in the response of maize to arsenic
      exposure.
AB  - To support the key role of glutathione (GSH) in the mechanisms of tolerance and
      accumulation of arsenic in plants, this work examines the impact of several
      effectors of GSH synthesis or action in the response of maize (Zea mays L.) to
      arsenic. Maize was exposed in hydroponics to iso-toxic rates of 150 MUM arsenate
      or 75 MUM arsenite for 9 days and GSH effectors, flurazole (an herbicide
      safener), l-buthionine-sulfoximine (BSO, a known inhibitor of GSH biosynthesis),
      and dimercaptosuccinate (DMS) and dimercaptopropanesulfonate (DMPS) (two thiols
      able to displace GSH from arsenite-GSH complexes) were assayed. The main
      responses of plants to arsenic exposure consisted of a biomass reduction (fresh
      weight basis) of about 50%, an increase of non-protein thiol (NPTs) levels
      (especially in the GSH precursor gamma-glutamylcysteine and the phytochelatins
      PC2 and PC3) in roots, with little effect in shoots, and an accumulation of
      between 600 and 1000 ppm of As (dry weight basis) in roots with very little
      translocation to shoots. Growth inhibition caused by arsenic was partially or
      completely reversed in plants co-treated with flurazole and arsenate or arsenite,
      respectively, highly exacerbated in plants co-treated with BSO, and not modified
      in plants co-treated with DMS or DMPS. These responses correlated well with an
      increase of both NPTs levels in roots and glutathione transferase activity in
      roots and shoots due to flurazole treatment, the decrease of NPTs levels in roots
      caused by BSO and the lack of effect on NPT levels caused by both DMS and DMPS.
      Regarding to arsenic accumulation in roots, it was not modified by flurazole,
      highly reduced by BSO, and increased between 2.5- and 4.0-fold by DMS and DMPS.
      Therefore, tolerance and accumulation of arsenic by maize could be manipulated
      pharmacologically by chemical effectors of GSH.

PMID- 22418431
TI  - Pulmonary surfactant protein A protects lung epithelium from cytotoxicity of
      human beta-defensin 3.
AB  - Defensins are important molecules in the innate immune system that eliminate
      infectious microbes. They also exhibit cytotoxicity against host cells in higher
      concentrations. The mechanisms by which hosts protect their own cells from
      cytotoxicity of defensins have been poorly understood. We found that the
      cytotoxicity of human beta-defensin 3 (hBD3) against lung epithelial cells was
      dose-dependently attenuated by pulmonary surfactant protein A (SP-A), a collectin
      implicated in host defense and regulation of inflammatory responses in the lung.
      The direct interaction between SP-A and hBD3 may be an important factor in
      decreasing this cytotoxicity because preincubation of epithelial cells with SP-A
      did not affect the cytotoxicity. Consistent with in vitro analysis, intratracheal
      administration of hBD3 to SP-A(-/-) mice resulted in more severe tissue damage
      compared with that in WT mice. These data indicate that SP-A protects lung
      epithelium from tissue injury caused by hBD3. Furthermore, we found that the
      functional region of SP-A lies within Tyr(161)-Lys(201). Synthetic peptide
      corresponding to this region, tentatively called SP-A Y161-G200, also inhibited
      cytotoxicity of hBD3 in a dose-dependent manner. The SP-A Y161-G200 is a
      candidate as a therapeutic reagent that prevents tissue injury during
      inflammation.

PMID- 22418432
TI  - Developmental truncations of connexin 50 by caspases adaptively regulate gap
      junctions/hemichannels and protect lens cells against ultraviolet radiation.
AB  - The gap junction-forming connexin (Cx) 50 is truncated gradually during lens
      development. Premature cleavage of lens connexins is thought to be associated
      with cataract formation. We have shown previously that Cx50 is likely to be
      cleaved by caspase-3 like protease during chick lens development. Here, using
      HPLC-electrospray tandem mass spectrometry, we mapped two cleavage sites at the C
      terminus of Cx50 after Glu-368 and Asp-379 and identified caspase-3 and caspase-1
      as the responsible proteases, respectively. The activity of caspase-1, like
      caspase-3, was detected in the outer cortex increased during lens development,
      which coincided with the accumulation of the truncated fragments of Cx50 in the
      core region of the lens. The truncated Cx50 fragments present in older lenses
      were reproduced in the younger lens after treatment with UV radiation; this
      cleavage could be partially blocked by caspase-1/3-specific inhibitors.
      Interestingly, as compared with full-length Cx50, caspase-truncated Cx50 showed a
      dramatic decrease in gap junction coupling and a loss of hemichannel function.
      Furthermore, expression of caspase-truncated Cx50 fragments increased cell
      viability against UV radiation as compared with full-length Cx50. Together, these
      results suggest that both caspase-1 and -3 are responsible for the cleavage at
      the C terminus of Cx50 during lens development. The reduction of gap junction
      coupling and closure of hemichannels formed by truncated Cx50 are likely to
      adaptively protect cells against elevated oxidative stress associated with lens
      aging.

PMID- 22418433
TI  - Neutrophil gelatinase-associated lipocalin (NGAL) expression is dependent on the
      tumor-associated sigma-2 receptor S2RPgrmc1.
AB  - Tumor invasion is a critical step in the spread of cancer. S2R (sigma-2
      receptor)/Pgrmc1 (progesterone receptor membrane component 1) is a cytochrome
      b(5)-related drug-binding orphan receptor essential for tumor formation and
      invasion. Secretory proteins drive these processes, so we screened for
      S2R(Pgrmc1)-dependent secreted proteins using antibody arrays. S2R(Pgrmc1)
      markedly regulated the expression of NGAL/LCN2 (neutrophil gelatinase-associated
      lipocalin/lipocalin 2), a secreted glycoprotein that binds to MMP-9 (matrix
      metalloproteinase 9) and protects it from degradation. S2R(Pgrmc1) knock-down
      blocked NGAL/LCN2 expression at the protein and RNA levels and decreased MMP9
      activity. NGAL expression was required for MMP-9 activity and tumor formation.
      S2R(Pgrmc1) associates with EGFR and increases EGFR levels at the plasma
      membrane, and the EGFR inhibitors erlotinib and AG1478, as well as Akt and ERK
      inhibitors, suppressed the NGAL/LCN2 RNA and protein levels. NGAL is
      transcriptionally regulated by NFkappaB, and S2R(Pgrmc1) knock-down decreased the
      NFkappaB subunit p65/RelA acetylation, phosphorylation, and activation. In
      S2R(Pgrmc1) knock-down cells, p65 acetylation was reversed by inhibitors of
      histone deacetylase 1, and the inhibitors partially restored NGAL levels. Our
      results are consistent with a model in which S2R(Pgrmc1) increases NGAL/LCN2
      levels by activating NFkappaB via EGFR.

PMID- 22418435
TI  - Plasma membrane potential oscillations in insulin secreting Ins-1 832/13 cells do
      not require glycolysis and are not initiated by fluctuations in mitochondrial
      bioenergetics.
AB  - Oscillations in plasma membrane potential play a central role in glucose-induced
      insulin secretion from pancreatic beta-cells and related insulinoma cell lines.
      We have employed a novel fluorescent plasma membrane potential (Deltapsi(p))
      indicator in combination with indicators of cytoplasmic free Ca(2+)
      ([Ca(2+)](c)), mitochondrial membrane potential (Deltapsi(m)), matrix ATP
      concentration, and NAD(P)H fluorescence to investigate the role of mitochondria
      in the generation of plasma membrane potential oscillations in clonal INS-1
      832/13 beta-cells. Elevated glucose caused oscillations in plasma membrane
      potential and cytoplasmic free Ca(2+) concentration over the same concentration
      range required for insulin release, although considerable cell-to-cell
      heterogeneity was observed. Exogenous pyruvate was as effective as glucose in
      inducing oscillations, both in the presence and absence of 2.8 mM glucose.
      Increased glucose and pyruvate each produced a concentration-dependent
      mitochondrial hyperpolarization. The causal relationships between pairs of
      parameters (Deltapsi(p) and [Ca(2+)](c), Deltapsi(p) and NAD(P)H, matrix ATP and
      [Ca(2+)](c), and Deltapsi(m) and [Ca(2+)](c)) were investigated at single cell
      level. It is concluded that, in these beta-cells, depolarizing oscillations in
      Deltapsi(p) are not initiated by mitochondrial bioenergetic changes. Instead,
      regardless of substrate, it appears that the mitochondria may simply be required
      to exceed a critical bioenergetic threshold to allow release of insulin. Once
      this threshold is exceeded, an autonomous Deltapsi(p) oscillatory mechanism is
      initiated.

PMID- 22418434
TI  - Muscle-specific knock-out of NUAK family SNF1-like kinase 1 (NUAK1) prevents high
      fat diet-induced glucose intolerance.
AB  - NUAK1 is a member of the AMP-activated protein kinase-related kinase family.
      Recent studies have shown that NUAK1 is involved in cellular senescence and
      motility in epithelial cells and fibroblasts. However, the physiological roles of
      NUAK1 are poorly understood because of embryonic lethality in NUAK1 null mice.
      The purpose of this study was to elucidate the roles of NUAK1 in adult tissues.
      We determined the tissue distribution of NUAK1 and generated muscle-specific
      NUAK1 knock-out (MNUAK1KO) mice. For phenotypic analysis, whole body glucose
      homeostasis and muscle glucose metabolism were examined. Quantitative
      phosphoproteome analysis of soleus muscle was performed to understand the
      molecular mechanisms underlying the knock-out phenotype. Nuak1 mRNA was
      preferentially expressed in highly oxidative tissues such as brain, heart, and
      soleus muscle. On a high fat diet, MNUAK1KO mice had a lower fasting blood
      glucose level, greater glucose tolerance, higher insulin sensitivity, and higher
      concentration of muscle glycogen than control mice. Phosphoproteome analysis
      revealed that phosphorylation of IRS1 Ser-1097 was markedly decreased in NUAK1
      deficient muscle. Consistent with this, insulin signaling was enhanced in the
      soleus muscle of MNUAK1KO mice, as evidenced by increased phosphorylation of IRS1
      Tyr-608, AKT Thr-308, and TBC1D4 Thr-649. These observations suggest that a
      physiological role of NUAK1 is to suppress glucose uptake through negative
      regulation of insulin signaling in oxidative muscle.

PMID- 22418436
TI  - Disturbance of Ca2+ homeostasis converts pro-Met into non-canonical tyrosine
      kinase p190MetNC in response to endoplasmic reticulum stress in MHCC97 cells.
AB  - c-Met, the tyrosine-kinase receptor for hepatocyte growth factor, plays a
      critical role in the tumorigenesis of hepatocellular carcinoma (HCC). However,
      the underlying mechanism remains incompletely understood. The mature c-Met
      protein p190Met(alphabeta) (consists of a alpha subunit and a beta subunit) is
      processed from pro-Met. Here we show that pro-Met is processed into p190Met(NC)
      by sarco/endoplasmic reticulum calcium-ATPase (SERCA) inhibitor thapsigargin.
      p190Met(NC) compensates for the degradation of p190Met(alphabeta) and protects
      human HCC cells from apoptosis mediated by endoplasmic reticulum (ER) stress. In
      comparison with p190Met(alphabeta), p190Met(NC) is not cleaved and is expressed
      as a single-chain polypeptide. Thapsigargin-initiated p190Met(NC) expression
      depends on the disturbance of ER calcium homeostasis. Once induced, p190Met(NC)
      is activated independent of hepatocyte growth factor engagement. p190Met(NC)
      contributes to sustained high basal activation of c-Met downstream pathways
      during ER calcium disturbance-mediated ER stress. Both p38 MAPK-promoted glucose
      regulated protein 78 (GRP78) expression and sustained high basal activation of
      PI3K/Akt and MEK/ERK are involved in the cytoprotective function of p190Met(NC).
      Importantly, the expression of p190Met(NC) is detected in some HCC cases. Taken
      together, these data provide a potential mechanism to explain how c-Met promotes
      HCC cells survival in response to ER stress. We propose that context-specific
      processing of c-Met protein is implicated in HCC progression in stressful
      microenvironments.

PMID- 22418437
TI  - Naturally occurring eccentric cleavage products of provitamin A beta-carotene
      function as antagonists of retinoic acid receptors.
AB  - beta-Carotene is the major dietary source of provitamin A. Central cleavage of
      beta-carotene catalyzed by beta-carotene oxygenase 1 yields two molecules of
      retinaldehyde. Subsequent oxidation produces all-trans-retinoic acid (ATRA),
      which functions as a ligand for a family of nuclear transcription factors, the
      retinoic acid receptors (RARs). Eccentric cleavage of beta-carotene at non
      central double bonds is catalyzed by other enzymes and can also occur non
      enzymatically. The products of these reactions are beta-apocarotenals and beta
      apocarotenones, whose biological functions in mammals are unknown. We used
      reporter gene assays to show that none of the beta-apocarotenoids significantly
      activated RARs. Importantly, however, beta-apo-14'-carotenal, beta-apo-14'
      carotenoic acid, and beta-apo-13-carotenone antagonized ATRA-induced
      transactivation of RARs. Competitive radioligand binding assays demonstrated that
      these putative RAR antagonists compete directly with retinoic acid for high
      affinity binding to purified receptors. Molecular modeling studies confirmed that
      beta-apo-13-carotenone can interact directly with the ligand binding site of the
      retinoid receptors. beta-Apo-13-carotenone and the beta-apo-14'-carotenoids
      inhibited ATRA-induced expression of retinoid responsive genes in Hep G2 cells.
      Finally, we developed an LC/MS method and found 3-5 nm beta-apo-13-carotenone was
      present in human plasma. These findings suggest that beta-apocarotenoids function
      as naturally occurring retinoid antagonists. The antagonism of retinoid signaling
      by these metabolites may have implications for the activities of dietary beta
      carotene as a provitamin A and as a modulator of risk for cardiovascular disease
      and cancer.

PMID- 22418438
TI  - Characterization of DalS, an ATP-binding cassette transporter for D-alanine, and
      its role in pathogenesis in Salmonella enterica.
AB  - Expansion into new host niches requires bacterial pathogens to adapt to changes
      in nutrient availability and to evade an arsenal of host defenses. Horizontal
      acquisition of Salmonella Pathogenicity Island (SPI)-2 permitted the expansion of
      Salmonella enterica serovar Typhimurium into the intracellular environment of
      host cells by allowing it to deliver bacterial effector proteins across the
      phagosome membrane. This is facilitated by the SsrA-SsrB two-component regulatory
      system and a type III secretion system encoded within SPI-2. SPI-2 acquisition
      was followed by evolution of existing regulatory DNA, creating an expanded SsrB
      regulon involved in intracellular fitness and host infection. Here, we identified
      an SsrB-regulated operon comprising an ABC transporter in Salmonella. Biochemical
      and structural studies determined that the periplasmic solute-binding component,
      STM1633/DalS, transports D-alanine and that DalS is required for intracellular
      survival of the bacteria and for fitness in an animal host. This work exemplifies
      the role of nutrient exchange at the host-pathogen interface as a critical
      determinant of disease outcome.

PMID- 22418439
TI  - Six-transmembrane topology for Golgi anti-apoptotic protein (GAAP) and Bax
      inhibitor 1 (BI-1) provides model for the transmembrane Bax inhibitor-containing
      motif (TMBIM) family.
AB  - The Golgi anti-apoptotic protein (GAAP) is a hydrophobic Golgi protein that
      regulates intracellular calcium fluxes and apoptosis. GAAP is highly conserved
      throughout eukaryotes and some strains of vaccinia virus (VACV) and camelpox
      virus. Based on sequence, phylogeny, and hydrophobicity, GAAPs were classified
      within the transmembrane Bax inhibitor-containing motif (TMBIM) family. TMBIM
      members are anti-apoptotic and were predicted to have seven-transmembrane domains
      (TMDs). However, topology prediction programs are inconsistent and predicted that
      GAAP and other TMBIM members have six or seven TMDs. To address this discrepancy,
      we mapped the transmembrane topology of viral (vGAAP) and human (hGAAP), as well
      as Bax inhibitor (BI-1). Data presented show a six-, not seven-, transmembrane
      topology for vGAAP with a putative reentrant loop at the C terminus and both
      termini located in the cytosol. We find that this topology is also conserved in
      hGAAP and BI-1. This places the charged C terminus in the cytosol, and mutation
      of these charged residues in hGAAP ablated its anti-apoptotic function. Given the
      highly conserved hydrophobicity profile within the TMBIM family and recent
      phylogenetic data indicating that a GAAP-like protein may have been the ancestral
      progenitor of a subset of the TMBIM family, we propose that this vGAAP topology
      may be used as a model for the remainder of the TMBIM family of proteins. The
      topology described provides valuable information on the structure and function of
      an important but poorly understood family of proteins.

PMID- 22418440
TI  - Hyaluronic acid receptor CD44 deficiency is associated with decreased
      Cryptococcus neoformans brain infection.
AB  - Cryptococcus neoformans is a pathogenic yeast that can invade the brain and cause
      meningoencephalitis. Our previous in vitro studies suggested that the interaction
      between C. neoformans hyaluronic acid and human brain endothelial CD44 could be
      the initial step of brain invasion. In this report, we used a CD44 knock-out (KO
      or CD44(-/-)) mouse model to explore the importance of CD44 in C. neoformans
      brain invasion. Our results showed that C. neoformans-infected CD44 KO mice
      survived longer than the infected wild-type mice. Consistent with our in vitro
      results, the brain and cerebrospinal fluid fungal burden was reduced in CD44
      deficient mice. Histopathological studies showed smaller and fewer cystic lesions
      in the brains of CD44 KO mice. Interestingly, the cystic lesions contained C.
      neoformans cells embedded within their polysaccharide capsule and were surrounded
      by host glial cells. We also found that a secondary hyaluronic acid receptor,
      RHAMM (receptor of hyaluronan-mediated motility), was present in the CD44 KO
      mice. Importantly, our studies demonstrated an in vivo blocking effect of
      simvastatin. These results suggest that the CD44 and RHAMM receptors function on
      membrane lipid rafts during invasion and that simvastatin may have a potential
      therapeutic role in C. neoformans infections of the brain.

PMID- 22418441
TI  - Identification, characterization, and epitope mapping of human monoclonal
      antibody J19 that specifically recognizes activated integrin alpha4beta7.
AB  - Integrin alpha(4)beta(7) is a lymphocyte homing receptor that mediates both
      rolling and firm adhesion of lymphocytes on vascular endothelium, two of the
      critical steps in lymphocyte migration and tissue-specific homing. The rolling
      and firm adhesions of lymphocytes rely on the dynamic shift between the inactive
      and active states of integrin alpha(4)beta(7), which is associated with the
      conformational rearrangement of integrin molecules. Activation-specific
      antibodies, which specifically recognize the activated integrins, have been used
      as powerful tools in integrin studies, whereas there is no well characterized
      activation-specific antibody to integrin alpha(4)beta(7). Here, we report the
      identification, characterization, and epitope mapping of an activation-specific
      human mAb J19 against integrin alpha(4)beta(7). J19 was discovered by screening a
      human single-chain variable fragment phage library using an activated
      alpha(4)beta(7) mutant as target. J19 IgG specifically bound to the high affinity
      alpha(4)beta(7) induced by Mn(2+), DTT, ADP, or CXCL12, but not to the low
      affinity integrin. Moreover, J19 IgG did not interfere with alpha(4)beta(7)
      MAdCAM-1 interaction. The epitope of J19 IgG was mapped to Ser-331, Ala-332, and
      Ala-333 of beta(7) I domain and a seven-residue segment from 184 to 190 of
      alpha(4) beta-propeller domain, which are buried in low affinity integrin with
      bent conformation and only exposed in the high affinity extended conformation.
      Taken together, J19 is a potentially powerful tool for both studies on
      alpha(4)beta(7) activation mechanism and development of novel therapeutics
      targeting the activated lymphocyte expressing high affinity alpha(4)beta(7).

PMID- 22418443
TI  - Transglutaminase 2 promotes both caspase-dependent and caspase-independent
      apoptotic cell death via the calpain/Bax protein signaling pathway.
AB  - Transglutaminase 2 (TG2) is a versatile protein that is implicated in significant
      biological processes, including cell death and degenerative diseases. A possible
      role of TG2 in the apoptotic death of cancer cells induced by photodynamic
      therapy (PDT) was suggested recently; however, the mechanism by which TG2
      regulates apoptotic responses to PDT remains to be elucidated. In this study, we
      investigated the key signaling pathways stimulated during apoptotic cell death
      following PDT and whether inhibition of TG2 activation using pharmacological
      approaches and siRNAs affects the signaling pathways. PDT caused the release of
      both cytochrome c and apoptosis-inducing factor (AIF) by damaging mitochondria,
      which resulted in caspase-dependent and caspase-independent apoptotic cell death,
      respectively. Released AIF translocated to the nucleus and, synergistically with
      the caspase-dependent pathway, led to apoptotic cell death. Both the caspase
      cascade and the activation of AIF following PDT were mediated by TG2 activation.
      In addition, PDT-activated calpain was responsible for the sequential events of
      Bax translocation, the collapse of DeltaPsi(m), caspase-3 activation, and AIF
      translocation, all of which were provoked by TG2 activation. Together, these
      results demonstrate that PDT with a chlorin-based photosensitizer targets TG2 by
      activating calpain-induced Bax translocation, which induces apoptotic cell death
      through both caspase-dependent and AIF-mediated pathways. Moreover, these results
      indicate that TG2 may be a possible therapeutic target for PDT treatment of
      cancer.

PMID- 22418442
TI  - Structure-dependent pseudoreceptor intracellular traffic of adamantyl
      globotriaosyl ceramide mimics.
AB  - The verotoxin (VT) (Shiga toxin) receptor globotriaosyl ceramide (Gb(3)),
      mediates VT1/VT2 retrograde transport to the endoplasmic reticulum (ER) for
      cytosolic A subunit access to inhibit protein synthesis. Adamantyl Gb(3) is an
      amphipathic competitive inhibitor of VT1/VT2 Gb(3) binding. However, Gb(3)
      negative VT-resistant CHO/Jurkat cells incorporate adaGb(3) to become VT1/VT2
      sensitive. CarboxyadaGb(3), urea-adaGb(3), and hydroxyethyl adaGb(3),
      preferentially bound by VT2, also mediate VT1/VT2 cytotoxicity. VT1/VT2
      internalize to early endosomes but not to Golgi/ER. AdabisGb(3) (two deacyl
      Gb(3)s linked to adamantane) protects against VT1/VT2 more effectively than
      adaGb(3) without incorporating into Gb(3)-negative cells. AdaGb(3) (but not
      hydroxyethyl adaGb(3)) incorporation into Gb(3)-positive Vero cells rendered
      punctate cell surface VT1/VT2 binding uniform and subverted subsequent Gb(3)
      dependent retrograde transport to Golgi/ER to render cytotoxicity (reduced for
      VT1 but not VT2) brefeldin A-resistant. VT2-induced vacuolation was maintained in
      adaGb(3)-treated Vero cells, but vacuolar membrane VT2 was lost. AdaGb(3)
      destabilized membrane cholesterol and reduced Gb(3) cholesterol stabilization in
      phospholipid liposomes. Cholera toxin GM1-mediated Golgi/ER targeting was
      unaffected by adaGb(3). We demonstrate the novel, lipid-dependent, pseudoreceptor
      function of Gb(3) mimics and their structure-dependent modulation of endogenous
      intracellular Gb(3) vesicular traffic.

PMID- 22418444
TI  - WH(n) under pressure.
AB  - An initial observation of the formation of WH under pressure from W gaskets
      surrounding hydrogen in diamond anvil cells led to a theoretical study of
      tungsten hydride phases. At P = 1 atm no stoichiometry is found to be stable with
      respect to separation into the elements, but as the pressure is raised WH(n) (n =
      1-6, 8) stoichiometries are metastable or stable. WH and WH(4) are calculated to
      be stable at P > 15 GPa, WH(2) becomes stable at P > 100 GPa and WH(6) at P > 150
      GPa. In agreement with experiment, the structure computed for WH is anti-NiAs.
      WH(2) shares with WH a hexagonal arrangement of tungsten atoms, with hydrogen
      atoms occupying octahedral and tetrahedral holes. For WH(4) the W atoms are in a
      distorted fcc arrangement. As the number of hydrogens rises, the coordination of
      W by H increases correspondingly, leading to a twelve-coordinated W in WH(6). In
      WH(8) H(2) units also develop. All of the hydrides considered should be metallic
      at high pressure, though the Fermi levels of WH(4) and WH(6) lie in a deep
      pseudogap. Prodded by these theoretical studies, experiments were then undertaken
      to seek phases other than WH, exploring a variety of experimental conditions that
      would favor further reaction. Though a better preparation and characterization of
      WH resulted, no higher hydrides have as yet been found.

PMID- 22418445
TI  - Gadoxetate acid-enhanced MRI of hepatocellular carcinoma in a c-myc/TGFalpha
      transgenic mouse model including signal intensity and fat content: initial
      experience.
AB  - Genetically engineered mouse models, such as double transgenic c-myc/TGFalpha
      mice, with specific pathway abnormalities might be more successful at predicting
      the clinical response of hepatocellular carcinoma (HCC) treatment. But a major
      drawback of the tumour models is the difficulty of visualizing endogenously
      formed tumours. The optimal imaging procedure should be brief and minimally
      invasive. Magnetic resonance imaging (MRI) satisfies these criteria and
      gadoxetate acid-enhanced MRI improves the detection of HCC. Fat content is stated
      to be an additional tool to help assess tumour responses, for example, in cases
      of radiofrequency ablation. Therefore the aim of this study was to investigate if
      gadoxetate acid-enhanced MRI could be used to detect HCC in c-myc/TGFalpha
      transgenic mice by determining the relation between the signal intensity of HCC
      and normal liver parenchyma and the corresponding fat content as a diagnostic
      marker of HCC. In our study, 20 HCC in c-myc/TGFalpha transgenic male mice aged
      20-34 weeks were analyzed. On gadoxetate acid-enhanced MRI, the signal intensity
      was 752.4 for liver parenchyma and 924.5 for HCC. The contrast to noise ratio was
      20.4, the percentage enhancement was 267.1% for normal liver parenchyma and
      353.9% for HCC. The fat content was 11.2% for liver parenchyma and 16.2% for HCC.
      There was a correlation between fat content and signal intensity with r = 0.7791.
      All parameters were statistically significant with P < 0.05. Our data indicate
      that gadoxetate acid contrast enhancement allows sensitive detection of HCC in c
      myc/TGFalpha transgenic mice and determination of the fat content seems to be an
      additional useful parameter for HCC.

PMID- 22418446
TI  - [Potentially inappropriate prescriptions for the elderly: a study of health
      insurance reimbursements in Southeastern France].
AB  - BACKGROUND: This study conducted in the region of Provence-Alpes-Cote d'Azur
      (PACA) sought to assess the feasibility of constructing and using indicators of
      potentially inappropriate prescriptions for the elderly from health insurance
      reimbursement data. We present and discuss different indicators of inappropriate
      prescriptions for people aged 70 years or older (at-risk prescriptions, dangerous
      or at-risk coprescriptions, absence of necessary coprescriptions) and reports
      their prevalence in PACA. METHODS: The indicators were constructed from the
      French list of inappropriate prescriptions, national agency guidelines, and the
      advice of experts in the field. The indicators selected were applied to the
      databases of the PACA Salaried Workers' Health Insurance Fund for 2008 for all
      recipients aged 70 years or older and compared according to age, sex, chronic
      disease status, and, after standardization for age and sex, according to district
      of residence. RESULTS: In January 2009, 500,904 recipients aged 70 years or older
      were identified in the data base of the Salaried Workers' Health Insurance Fund,
      60.8% of whom were women and 52.1% of whom had approved coverage for a chronic
      disease. The potentially inappropriate prescriptions most frequently observed
      here, in decreasing order, were: prescription of an NSAID without the
      coprescription of gastric protection (28.1%); long-term benzodiazepine treatment
      (21.5%); prescription of long half-life benzodiazepine (14.9%), and long-term
      treatment with NSAIDs (11.6%). Overall, the prevalence of each increased
      significantly with age and was higher among women and people with chronic
      diseases. Significant variations were also observed between the different
      districts of PACA. CONCLUSION: Our results confirm that a substantial proportion
      of elderly people receive potentially inappropriate prescriptions. They also
      suggest that health insurance reimbursement data could be used in some
      prescription domains for monitoring trends in the potentially inappropriate
      prescriptions in the populations of various territories, provided that specific
      limitations are considered.

PMID- 22418447
TI  - Mechanisms of interaction between protozoan parasites and HIV.
AB  - PURPOSE OF REVIEW: This review summarizes the current knowledge on human
      immunodeficiency virus type 1 (hereinafter called HIV)/protozoan co-infections in
      the case of three important, although neglected, tropical diseases: malaria,
      trypanosomiasis (Chagas disease) and leishmaniasis. The HIV pandemic has modified
      the immunopathogenic, epidemiological and therapeutic aspects of these human
      diseases. RECENT FINDINGS: In-vitro data suggests that HIV favors Leishmania
      infection, whereas different parasites have contrasting effects on HIV. However,
      many of the previous models are a limited representation of the complex
      interactions within the host; this situation is particularly the case when
      microbial products are used in place of live parasites. SUMMARY: In the host,
      protozoan parasites generally enhance HIV replication and accelerate AIDS
      progression. HIV alters parasite pathogenesis, often worsening disease outcome.
      These aspects bring significant complications for the treatment of co-infected
      individuals.

PMID- 22418449
TI  - Epidemiology of malaria and helminth interaction:  a review from 2001 to 2011.
AB  - PURPOSE OF REVIEW: Malaria and helminthiasis are endemic in the same geographic
      areas, and may coinfect the same host. In the literature there is some
      controversy about the effect of helminth infection on malaria. RECENT FINDINGS:
      Large studies have been undertaken to clarify this interaction at the molecular
      and immunological level, we undertake a review of the epidemiology of the
      interaction between helminths and malaria in areas where both are endemic. A
      search of the literature from 2001 to 2011 showed that several studies have been
      conducted on the interaction of helminths and malaria. Most of the studies had a
      cross-sectional or longitudinal design, whereas few were interventional studies
      of school children and pregnant women. The main finding is that there is a trend
      toward a protective effect of Ascaris lumbricoides and Schistosoma hematobium,
      and worsening effect of hookworm and S. mansoni on the pathogenesis and incidence
      of malaria, respectively. It is important also to put emphasis on the general
      protective effect of helminth infection against severe malaria. SUMMARY:
      Hookworm, A. lumbricoides and Schistosoma species were found to associate
      differently with malaria, which might explain the conflicting reports on
      interaction between helminths and malaria. It is therefore important to further
      investigate these three major helminths in relation to malaria, using universally
      accepted 'gold standard' study designs, which would be able to clearly define the
      nature of the interaction between malaria and helminth species. A better
      understanding of helminths and malaria coinfection may strengthen malaria control
      programmes in coendemic areas.

PMID- 22418448
TI  - Impact of filarial infections on coincident intracellular pathogens: 
      Mycobacterium tuberculosis and Plasmodium falciparum.
AB  - PURPOSE OF REVIEW: To examine the consequences of the immune modulation seen in
      chronic filarial infection on responses to intracellular pathogens (and their
      antigens) that are often co-endemic with filarial infections, namely Plasmodium
      and Mycobacterium tuberculosis. RECENT FINDINGS: Much of the recent data on
      filaria/mycobacteria or filaria/Plasmodium co-infection has focused on the
      modulation of mycobacteria-specific or malaria-specific responses by chronic
      filarial infection. As such, filarial infections very clearly alter the magnitude
      and quality of the mycobacteria-specific or malaria-specific cytokine responses,
      responses that have been typically associated with control of these intracellular
      pathogens. SUMMARY: Although phylogenetically distinct, mycobacteria and
      Plasmodium spp. often share the same geographical niche with filarial infections.
      The complex interplay between filarial parasites that are associated with
      immunomodulation and those microbial pathogens that require a proinflammatory or
      unmodulated response for their control is easily demonstrable ex vivo, but
      whether this interplay affects disease outcome in tuberculosis or malaria remains
      an open question.

PMID- 22418451
TI  - Explaining educational differences in adolescent substance use and early sexual
      debut: the role of parents and peers.
AB  - Previous studies from a wide variety of European countries have demonstrated that
      low educated adolescents engage more frequently in health risk behaviors compared
      to high educated adolescents. The present study investigates the mediating roles
      of parental knowledge and time spent with peers in this relationship. Data were
      retrieved from a nationally representative sample of 12- to 16-year old Dutch
      adolescents (N=5422). Risk behaviors were measured by adolescents' report of
      daily smoking, binge drinking and cannabis use in the previous month, and sexual
      debut before age 17. Low educated adolescents indicated that their parents had
      less knowledge on their whereabouts and reported spending more time with peers
      than high educated adolescents. Both factors mediated the relationship with
      health risk behaviors. These results hint to parenting practices and adolescent
      peer relations as points of reference for prevention and intervention work aiming
      to reduce educational inequalities in adolescent health risk behaviors.

PMID- 22418450
TI  - Troubles never come alone.

PMID- 22418452
TI  - Adolescents' financial literacy: the role of financial socialization agents,
      financial experiences, and money attitudes in shaping financial literacy among
      South Korean youth.
AB  - The purpose of this study was to test the relationships between financial
      socialization agents, financial experiences, money attitudes, demographic
      characteristics, and the financial literacy of Korean adolescents. Using the 2006
      Korean National Financial Literacy Test Survey for Adolescents (N = 1185), a
      series of regression analyses were performed to determine the factors related to
      financial literacy. It was found that those who chose media as their primary
      financial socialization agent, and those who had a bank account, exhibited higher
      levels of financial literacy. Among the sample, those who saw money as good or as
      a reward for efforts tended to report higher levels of financial literacy, while
      those perceiving money in terms of avoidance or achievement had lower levels of
      financial literacy. Students with mid-range monthly allowances showed higher
      levels of financial literacy compared to the highest allowance group.
      Implications for financial educators, policy makers, and researchers are
      provided.

PMID- 22418453
TI  - Clinical and epidemiological features of 2009 pandemic H1N1 influenza differ
      slightly according to seroprevalence status during the second wave in the general
      population in Mexico.
AB  - BACKGROUND: Clinical features of pandemic H1N1 have been derived from lab
      confirmed, hospitalized, or critically ill subjects. This report describes the
      clinical features of H1N1 and their prevalence from non-confirmed subjects
      according to seroprevalence status in Mexico. The  objective was to determine the
      prevalence of these clinical features from non-confirmed cases of pandemic H1N1
      and to compare them according to seroprevalence status in northern Monterrey,
      Mexico, during 2009, and to identify the predictive signs and symptoms; there
      have been no prior  serologic studies in Mexico. METHODS: During November
      December 2009, 2,222 volunteers, ages 6-99 years, were categorized into 3
      symptomatic groups: influenza-like illness, respiratory illness, and non
      respiratory illness. Antibodies against influenza A/H1N1/2009 were determined  by
      a virus-free enzyme-linked immunosorbent assay (ELISA) method. Demographics and
      clinical presentation were assessed through face-to-face questionnaire, and the
      association with seroprevalence status was determined and compared. RESULTS:
      Overall seroprevalence was 39%. Of the seropositive  subjects, 67% were
      symptomatic and 33% were asymptomatic. Seventy-one percent of seropositive
      symptomatic subjects reported respiratory illness, 17% reported non-respiratory
      symptoms, and 12% reported influenza-like illness. The most common symptoms were
      rhinorrhea/nasal congestion (93%) and  headache (83%). No significant difference
      was found between the symptom profiles of the seropositive group, compared to the
      seronegative one, nor of the median duration of symptoms. The seropositive group
      had a significantly elevated proportion of influenza-like illness (12%), compared
      to  the seronegative group (8%). The proportion of subjects who took days off and
      who sought medical attention was significantly higher in the seropositive group.
      No single symptom was associated as a predictor of seropositiveness. CONCLUSIONS:
      One third of the seropositive subjects were asymptomatic,  and few had an
      influenza-like illness. No difference was found in the symptom profiles of the
      seropositive and seronegative groups. No single symptom predicted
      seropositiveness. Large scale population studies are needed, especially in
      Mexico, to characterize clinical syndromes.

PMID- 22418454
TI  - Detection of hepatitis C virus RNA in dried blood spots.
AB  - BACKGROUND: An estimated 130-170 million people worldwide are chronically
      infected with HCV.(1) In Europe the highest prevalence of HCV infections is in
      the IDU population.(2) As traditional HCV screening relies on the detection of
      HCV antibody or HCV RNA in blood, screening in high-risk groups such as IDU is
      difficult due to poor venous access caused by damaged veins. OBJECTIVES: In this
      study DBS was evaluated as an alternative sample type to blood for the detection
      of HCV RNA. STUDY DESIGN: The endpoint detection limit, inter-assay and intra
      assay variability of the method were determined. The DBS method was compared to
      our routine frontline assay using a panel of paired DBS and blood samples. The
      effect of different storage temperatures and length of storage time on the
      stability of HCV RNA in DBS was also assessed. RESULTS: The endpoint detection
      limit of the method based on results from mock DBS was 250 IU/ml. The method was
      shown to be precise and robust. The sensitivity and specificity of the method was
      found to be 100% and 95.8%, respectively. No significant variation in the
      stability of HCV RNA in DBS over a 1 year period at a range of different
      temperatures was observed. CONCLUSIONS: A sensitive and stable method was
      developed for the detection of HCV RNA in DBS. Screening high-risk populations
      using DBS as a sample type may improve uptake of HCV testing by increasing
      opportunity for patients to be tested and consequently increasing access to
      treatment.

PMID- 22418455
TI  - Transmission of HBV infection from mothers HBsAg positive to infants need to more
      attention.

PMID- 22418456
TI  - Prevalence, genotype diversity and determinants of anal HPV infection in HIV
      uninfected men having sex with men.
AB  - BACKGROUND: Anal human papillomavirus (HPV) infection is very common in men
      having sex with men (MSM), but the available data on its burden and
      characteristics mainly concern HIV-infected individuals. OBJECTIVES: This study
      aimed to assess the prevalence, spectrum of genotypes, and determinants of the
      anal HPV infection in metropolitan HIV-1 uninfected MSM. STUDY DESIGN: A cohort
      of 258 MSM (median age 32 years, IQR 26-39) enrolled at an STI Clinic was
      screened for anal HPV infection using a highly sensitive PCR-based genotyping
      method. Medical history and behavioral data were collected. RESULTS: Overall,
      74.8% of the MSM were HPV-positive, with 56.2% of the participants being infected
      by high-risk (HR) types. A multiple infection was detected in 65.3% of the HPV
      positive MSM, with up to 10 different HPV types detected in the same sample. A
      broad spectrum of infecting HPV types was observed, with 36 different types found
      overall and HPV16 representing the most common type (17.8%). The lifetime and
      recent number of sexual partners as well as having receptive anal sex were
      significantly associated with the anal HPV infection, confirming the role of
      sexual behavior in risk of HPV infection. However, neither younger age at first
      intercourse nor inconsistent use of condom was significantly associated with the
      infection. CONCLUSIONS: The present findings highlight the need to create a more
      significant awareness about the risk of anal HPV infection among HIV-uninfected
      MSM and warrant the investigation of possible anal intraepithelial lesions,
      particularly in view of the increasing anal cancer incidence in high-risk
      populations.

PMID- 22418457
TI  - Biological characterization and phylogenetic analysis of a novel genetic group of
      Newcastle disease virus isolated from outbreaks in commercial poultry and from
      backyard poultry flocks in Pakistan.
AB  - Newcastle disease (ND) is a contagious viral disease of many avian species
      particularly domestic poultry, and is responsible for devastating outbreaks in
      the poultry industries around the globe. In spite of its importance and
      endemicity in Southern Asia, data on the genetic nature of the viruses and
      epizootiological information of the disease is scarce. In this study, six
      isolates from an emerging wave of ND outbreaks in the north of Pakistan and two
      isolates from healthy poultry flocks were biologically and genetically
      characterized. Based on pathogenicity indices such as intracerebral pathogenicity
      index (ICPI), mean death time (MDT) and cleavage motifs in the fusion protein,
      all these isolates were classified as virulent. Phylogenetic analysis of the
      fusion (F), hemagglutinin-neuraminidase (HN) and matrix (M) genes indicated the
      emergence of a novel genetic group within lineage 5, distinct from isolates
      previously reported in the region. Several mutations in the neutralizing epitopes
      and functionally important motifs of the F and HN genes pose a need for re
      evaluation of the currently used vaccine and vaccination practices. The
      characteristics of Newcastle disease virus (NDV) as virulent (F protein cleavage
      site, ICPI and MDT) in apparently healthy backyard poultry (BYP) explain that BYP
      can play crucial role in the epizootiology and spread of the disease. The present
      investigation provides essential information on the genetic nature of NDV
      circulating in Pakistan and its implication on disease diagnosis and control.
      Furthermore, these investigations emphasize the importance of continuous
      surveillance of ND in developing countries.

PMID- 22418458
TI  - Ventilatory threshold during incremental running can be estimated using EMG
      shorts.
AB  - The present study examined whether shorts with textile electromyographic (EMG)
      electrodes can be used to detect second ventilatory threshold (V(T2)) during
      incremental treadmill running. Thirteen recreationally active (REC) and eight
      endurance athletes were measured for EMG, heart rate, blood lactate and
      respiratory gases during VO(2max) test (3 min ramps, 1 km.h(-1) increments).
      V(T)(2), onset of blood lactate accumulation (OBLA) and EMG threshold (EMG(T))
      were determined. In athletes, OBLA occurred at 56 +/- 6 mL.kg(-1).min(-1), V(T2)
      occurred at 59 +/- 6 mL.kg(-1).min(-1), and EMG(T) at 62 +/- 6 mL.kg(-1).min(-1)
      without significant differences between methods (analysis of variance: ANOVA). In
      REC participants, OBLA occurred at 40 +/- 10 mL.kg(-1).min(-1), V(T2) occurred at
      43 +/- 7 mL.kg(-1).min(-1), and EMG(T) at 41 +/- 9 mL.kg(-1).min(-1) without
      significant differences between methods (ANOVA). For the entire group,
      correlation between EMG(T) and V(T2) was 0.86 (P < 0.001) and 0.84 (P < 0.001)
      between EMG(T) and OBLA. Limits of agreement between EMG(T) and V(T2) were
      narrower in athletes than in REC participants. Thus, it is concluded that
      estimation of V(T2) using EMG(T) in athletes is more valid than in REC
      participants. In practice, experienced runners could use online feedback from EMG
      garments to monitor whether their running intensity is near V(T2).

PMID- 22418459
TI  - Propagation beam consideration for 3D THz computed tomography.
AB  - In this paper, a model of the beam propagation is developed according to the
      physical properties of THz waves used in THz computed tomography (CT) scan
      imaging. This model is first included in an acquisition simulator to observe and
      estimate the impact of the Gaussian beam intensity profile on the projection
      sets. Second, the model is introduced in several inversion methods as a
      convolution filter to perform efficient tomographic reconstructions of simulated
      and real acquired objects. Results obtained with three reconstruction methods
      (BFP, SART and OSEM) are compared to the techniques proposed in this paper. We
      will demonstrate an increase of the overall quality and accuracy of the 3D
      reconstructions.

PMID- 22418460
TI  - Characterization of the resolving power and contrast transfer function of a
      transmission X-ray microscope with partially coherent illumination.
AB  - The achievable spatial resolution and the contrast transfer function (CTF) are
      key parameters characterizing an X-ray microscope. We measured the spatial
      resolution and the contrast transfer function of the transmission X-ray
      microscope (TXM) at the electron storage ring BESSY II. The TXM uses the
      radiation of an undulator source and operates under partially coherent
      illumination conditions. For spatial resolutions down to 25 nm, our measurements
      of the CTF's are in good agreement with theoretical CTF data for partial
      coherence. With higher resolution zone plate objectives, we measured a spatial
      resolution (half-pitch) of 11 nm in 1st and 3rd order of diffraction. However,
      with these objectives the stray light level increases significantly.

PMID- 22418461
TI  - Tunable slow and fast light device based on a carbon nanotube resonator.
AB  - We report a tunable slow and fast light device based on a carbon nanotube
      resonator, in the presence of a strong pump laser and a weak signal laser.
      Detailed analysis shows that the signal laser displays the superluminal and
      ultraslow light characteristics via passing through a suspended carbon nanotube
      resonator, while the incident pump laser is on- and off-resonant with the exciton
      frequency, respectively. In particular, the fast and slow light correspond to the
      negative and positive dispersion, respectively, associating with the vanished
      absorption. The bandwidth of the signal spectrum is determined by the vibration
      decay rate of carbon nanotube.

PMID- 22418462
TI  - A wide spectral range single-photon avalanche diode fabricated in an advanced 180
      nm CMOS technology.
AB  - We present a single-photon avalanche diode (SPAD) with a wide spectral range
      fabricated in an advanced 180 nm CMOS process. The realized SPAD achieves 20 %
      photon detection probability (PDP) for wavelengths ranging from 440 nm to 820 nm
      at an excess bias of 4 V, with 30 % PDP at wavelengths from 520 nm to 720 nm.
      Dark count rates (DCR) are at most 5 kHz, which is 30 Hz/MUm2, at an excess bias
      of 4V when we measure 10 MUm diameter active area structure. Afterpulsing
      probability, timing jitter, and temperature effects on DCR are also presented.

PMID- 22418463
TI  - Terahertz refractive index sensors using dielectric pipe waveguides.
AB  - A dielectric pipe waveguide is successfully demonstrated as a terahertz
      refractive index sensor for powder and liquid-vapor sensing. Without additional
      engineered structures, a simple pipe waveguide can act as a terahertz resonator
      based on anti-resonant reflecting guidance, forming multiple resonant
      transmission-dips. Loading various powders in the ring-cladding or inserting
      different vapors into the hollow core of the pipe waveguide leads to a
      significant shift of resonant frequency, and the spectral shift is related to the
      refractive-index change. The proven detection limit of molecular density could be
      reduced to 1.6nano-mole/mm<sup>3</sup> and the highest sensitivity is
      demonstrated at around 22.2GHz/refractive-index-unit (RIU), which is comparable
      to the best THz molecular sensor [Appl. Phys. Lett. 95, 171113 (2009)].

PMID- 22418464
TI  - Components for silicon plasmonic nanocircuits based on horizontal Cu-SiO2-Si-SiO2
      Cu nanoplasmonic waveguides.
AB  - We report systematic results on the development of horizontal Cu-SiO2-Si-SiO2-Cu
      nanoplasmonic waveguide components operating at 1550-nm telecom wavelengths,
      including straight waveguides, sharp 90 degrees  bends, power splitters, and Mach
      Zehnder interferometers (MZIs). Owing to the relatively low loss for propagating
      (~0.3 dB/um) and for 90 degrees  sharply bending (~0.73 dB/turn), various
      ultracompact power splitters and MZIs are experimentally realized on a silicon-on
      insulator (SOI) platform using standard CMOS technology. The demonstrated
      splitters exhibit a relatively low excess loss and the MZIs exhibit good
      performance such as high extinction ratio of ~18 dB and low normalized insertion
      loss of ~1.7 dB. The experimental results of these devices agree well with those
      predicted from numerical simulations with suitable Cu permittivity data.

PMID- 22418465
TI  - Development of a polarization-insensitive thermophotovoltaic emitter with a
      binary grating.
AB  - A wavelength-selective but polarization-insensitive thermophotovoltaic emitter
      was numerically developed with a binary tungsten grating and its appealing
      emittance spectra were demonstrated with analysis. Ranges of emitter dimensions
      were preliminarily confined with the excitation of the surface plasmon polariton,
      cavity resonance, and Wood's anomaly at specified wavelengths. Then, a hybrid
      scheme (the rigorous coupled wave analysis together with a genetic algorithm) was
      able to finely tailor the grating profile such that emittance could be
      significantly enhanced in the near infrared region. The peak emittance at the
      transverse electric and transverse magnetic polarizations was 0.997 and 0.935,
      respectively. The emittance was actually almost twice that from a plain tungsten
      plate at short wavelengths but significantly reduced at long wavelengths.
      Moreover, such spectral emittance is insensitive to the polarization and 5%
      dimension modification, making the emitter ideal for thermophotovoltaic
      applications. Patterns of electromagnetic fields and Poynting vectors were able
      to confirm the excitation of physical mechanisms.

PMID- 22418466
TI  - Laser emission from a solar-pumped fiber.
AB  - We report the realization of a solar-pumped fiber laser (SPFL) using a double
      clad (a center core/ an inner clad working also as optical waveguide/ an outer
      clad) Nd-doped fluoride optical fiber as a laser medium. With a compact off-axis
      parabolic mirror of 5 cm in aperture diameter, the natural sunlight is
      concentrated by a factor 104, and introduced partly into the core of the fiber
      and partly into the inner clad in which the light is guided in some distance and
      transferred to the core after all. We have obtained clear laser spectrum
      characteristics with approximately 0.01 nm full-width-half-maximum of the laser
      line at the peak wavelength of 1053.7 nm, a low-lasing threshold of 49.1 mW, a
      slope efficiency of 6.6%, and a total efficiency of 1.76%. Further optimization
      of the medium properties, optical cavity, and concentration technique will yield
      higher efficiency and lower threshold.

PMID- 22418467
TI  - Position and orientation estimation of fixed dipole emitters using an effective
      Hermite point spread function model.
AB  - We introduce a method for determining the position and orientation of fixed
      dipole emitters based on a combination of polarimetry and spot shape detection. A
      key element is an effective Point Spread Function model based on Hermite
      functions. The model offers a good description of the shape variations with
      dipole orientation and polarization detection channel, and provides computational
      advantages over the exact vectorial description of dipole image formation. The
      realized localization uncertainty is comparable to the free dipole case in which
      spots are rotationally symmetric and can be well modeled with a Gaussian. This
      result holds for all dipole orientations, for all practical signal levels, and
      for defocus values within the depth of focus, implying that the massive
      localization bias for defocused emitters with tilted dipole axis found with
      Gaussian spot fitting is eliminated.

PMID- 22418468
TI  - Excimer laser micromachining of aspheric microlens arrays based on optimal
      contour mask design and laser dragging method.
AB  - This paper presents an improved excimer laser micromachining method for
      fabricating arrayed microstructures with a predesigned surface profile. The
      proposed method is developed from a conventional biaxial laser dragging method,
      but numerical analysis and optimal pattern design on the contour mask are
      introduced so that the machined surface profiles can be well controlled and
      matched to the designed profiles. To demonstrate the capability of this new
      approach, an array of aspheric microlenses that have analog surfaces for
      minimizing the focal spot sizes of the lenses is designed and fabricated. An
      array of 10*10 microlenses with an aperture size of 100 MUm and a designed
      aspheric profile are obtained experimentally. The machined surface profiles are
      closely matched to their designed ones, with a profile deviation of less than 1
      MUm. Furthermore, the machined surfaces are smooth, with an average surface
      roughness of around 2 nm. Optical measurements on these machined aspheric
      microlenses show minimized focal spot sizes approaching their optical diffraction
      limits.

PMID- 22418469
TI  - Ultraviolet photodetector with high internal gain enhanced by TiO2/SrTiO3
      heterojunction.
AB  - In this letter, TiO2 nanocrystalline film was prepared on SrTiO3 (001) substrate
      to form an n-n heterojunction active layer. Interdigitated Au electrodes were
      deposited on the top of TiO2 film to fabricate modified HMSM (heterojunction
      metal-semiconductor-metal) ultraviolet photodetector. At 10 V bias, the dark
      current of the detector was only 0.2 nA and the responsivity was 46.1 A/W at 260
      nm. The rise and fall times of the device were 3.5 ms and 1.4 s, respectively.
      The TiO2/SrTiO3 heterojunction contributed a lot to the high responsivity and
      reduced the fall time, which improved the device performance effectively. These
      results demonstrate the excellent application of TiO2/SrTiO3 heterojunction in
      fabricating high performance UV photodetectors.

PMID- 22418470
TI  - Solving inverse problems for optical scanning holography using an adaptively
      iterative shrinkage-thresholding algorithm.
AB  - Optical scanning holography (OSH) records a three-dimensional object into a two
      dimensional hologram through two-dimensional optical scanning. The recovery of
      sectional images from the hologram, termed as an inverse problem, has been
      previously implemented by conventional methods as well as the use of l2 norm.
      However, conventional methods require time consuming processing of section by
      section without eliminating the defocus noise and the l2 norm method often
      suffers from the drawback of over-smoothing. Moreover, these methods require the
      whole hologram data (real and imaginary parts) to eliminate the twin image noise,
      whose computation complexity and the sophisticated post-processing are far from
      desirable. To handle these difficulties, an adaptively iterative shrinkage
      thresholding (AIST) algorithm, characterized by fast computation and adaptive
      iteration, is proposed in this paper. Using only a half hologram data, the
      proposed method obtained satisfied on-axis reconstruction free of twin image
      noise. The experiments of multi-planar reconstruction and improvement of depth of
      focus further validate the feasibility and flexibility of our proposed AIST
      algorithm.

PMID- 22418471
TI  - Non-iterative characterization of few-cycle laser pulses using flat-top gates.
AB  - We demonstrate a method for broadband laser pulse characterization based on a
      spectrally resolved cross-correlation with a narrowband flat-top gate pulse.
      Excellent phase-matching by collinear excitation in a microscope focus is
      exploited by degenerate four-wave mixing in a microscope slide. Direct group
      delay extraction of an octave spanning spectrum which is generated in a highly
      nonlinear fiber allows for spectral phase retrieval. The validity of the
      technique is supported by the comparison with an independent second-harmonic
      fringe-resolved autocorrelation measurement for an 11 fs laser pulse.

PMID- 22418472
TI  - Real-time relighting of digital holograms based on wavefront recording plane
      method.
AB  - Relighting is an important technique in photography which enables the optical
      properties of a picture to be modified without retaking it again. However,
      different from an optical image, a digital hologram cannot be relit by simply
      varying the value of individual pixel, as each of them is representing holistic
      information of the entire object scene. In this paper, we propose a fast method
      for the relighting of a digital hologram. First, the latter is projected to a
      virtual wavefront recording plane (WRP) that is located close to the object
      scene. Next, the WRP is relit, and subsequently expanded into a full hologram.
      Experiment results have demonstrated that our proposed method is capable of
      relighting a 2048x2048 hologram at a rate of over 50 frames per second. To the
      best of our knowledge, this is the first time relighting is considered in the
      context of holography.

PMID- 22418473
TI  - Long lifetime air plasma channel generated by femtosecond laser pulse sequence.
AB  - Lifetime of laser plasma channel is significantly prolonged using femtosecond
      laser pulse sequence, which is generated from a chirped pulse amplification laser
      system with pure multi-pass amplification chain. Time-resolved fluorescence
      images and electrical conductivity measurement are used to characterize the
      lifetime of the plasma channel. Prolongation of plasma channel lifetime up to
      microsecond level is observed using the pulse sequence.

PMID- 22418474
TI  - A multi-core holey fiber based plasmonic sensor with large detection range and
      high linearity.
AB  - We present and numerically characterize a closed-form multi-core holey fiber
      based plasmonic sensor. The coupling properties of the specific modes are
      investigated comprehensively by the finite element method. It is found that not
      only phase matching but also loss matching plays a key role in the coupling
      process between the fundamental mode and plasmonic mode. The coupling transforms
      from incomplete coupling to complete coupling with increasing analyte RI. An
      average sensitivity of 2929.39 nm/RIU in the sensing range 1.33-1.42, and 9231.27
      nm/RIU in 1.43-1.53 with high linearity is obtained. The dynamic sensing range is
      the largest among the reported holey fiber based plasmonic sensors, to the best
      of our knowledge.

PMID- 22418475
TI  - Extreme nonlinearities in InAs/InP nanowire gain media: the two-photon induced
      laser.
AB  - We demonstrate a novel laser oscillation scheme in an InAs / InP wire-like
      quantum dash gain medium. A short optical pulse excites carriers by two photon
      absorption which relax to the energy levels providing gain thereby enabling laser
      oscillations. The nonlinear dynamic interaction is analyzed and quantified using
      multi-color pump-probe measurements and shows a highly efficient nonlinear two
      photon excitation process which is larger by more than an order of magnitude
      compared to common quantum well and bulk gain media. The dynamic response of the
      nonlinearly induced laser line is characterized by spectrally resolved temporal
      response measurements, while changes incurring upon propagation in the
      stimulating short pulse itself are characterized by frequency resolved optical
      gating (FROG).

PMID- 22418476
TI  - Step-scan time-domain terahertz magneto-spectroscopy.
AB  - We present a novel approach for terahertz time-domain spectroscopy of magneto
      optic phenomena. The setup used in this work combines a tabletop pulsed magnet
      and a standard terahertz time-domain spectroscopy system. The approach is based
      on repetitive operation of the pulsed magnet and step-wise increment of the delay
      time of the time-domain spectroscopy system. The method is demonstrated by
      plotting the magneto-transmission spectra of linearly polarized THz pulses
      through the hole gas of a Ge sample and the electron gas of GaAs, InSb and InAs
      samples. Cyclotron resonance spectra are displayed in the frequency range from
      200 GHz to 2 THz and for a magnetic field up to 6 T. The GaAs spectra are
      analyzed in more detail using simulations based on the Drude model.

PMID- 22418477
TI  - Large aperture asymmetric Fabry Perot modulator based on asymmetric tandem
      quantum well for low voltage operation.
AB  - Large aperture image modulators used as demodulator in receiver path are an
      important component for the use in three dimensional (3D) image sensing. For
      practical applications, low voltage operation and high modulation performance are
      the key requirements for modulators. Here, we propose an asymmetric Fabry-Perot
      modulator (AFPM) with asymmetric tandem quantum wells (ATQWs) for 3D image
      sensing. By using ATQWs for the AFPM design, the device operated at -4.25V, and
      the operating voltage was significantly lower by about 23% compared to -5.5V of a
      conventional AFPM with 8nm thick multiple QW with a single QW thickness (SQWs),
      while achieving high reflectivity modulation in excess of 50%. The performance of
      the fabricated devices is in good agreement with theoretical calculations. The
      pixelated device shows a high modulation speed of 21.8 MHz over a large aperture
      and good uniformity. These results show that AFPM with ATQWs is a good candidate
      as an optical image modulator for 3D image sensing applications.

PMID- 22418478
TI  - Hybrid Ytterbium-doped large-mode-area photonic crystal fiber amplifier for long
      wavelengths.
AB  - A large-mode-area Ytterbium-doped photonic crystal fiber amplifier with build-in
      gain shaping is presented. The fiber cladding consists of a hexagonal lattice of
      air holes, where three rows are replaced with circular high-index inclusions.
      Seven missing air holes define the large-mode-area core. Light confinement is
      achieved by combined index and bandgap guiding, which allows for single-mode
      operation and gain shaping through distributed spectral filtering of amplified
      spontaneous emission. The fiber properties are ideal for amplification in the
      long wavelength regime of the Ytterbium gain spectrum above 1100 nm, and red
      shifting of the maximum gain to 1130 nm is demonstrated.

PMID- 22418479
TI  - Strain-insensitive temperature sensing with a dual polarization fiber grating
      laser.
AB  - In this paper, a strain-insensitive temperature sensor based on a dual
      polarization fiber grating laser is demonstrated. The laser is fabricated by
      inscribing two wavelength-matched Bragg gratings in an Er-doped fiber. It emits
      single-longitudinal-mode output in wavelength domain and generates a RF-domain
      signal as a beat note between the two polarization modes. A temperature sensor
      has been exploited by monitoring the beat frequency. The measured temperature
      sensitivity is -78.46 kHz/ degrees C. Theoretical analysis suggests that the
      temperature response is a result of both the differences in thermo-optic
      coefficient and thermal expansion between the core and cladding. In contrast, the
      sensor is almost insensitive to applied axial strain. We found that the strain
      insensitivity is due to the compensation between the strain-induced birefringence
      change and the effect of the elongation/material index change. The proposed
      sensor can be applied for reliable and precise measurement of temperature
      independently, towards the applications in structural integrity, oil-well
      monitoring, aerospace engineering, and process control.

PMID- 22418480
TI  - Preparation and transmission of low-loss azimuthally polarized pure single mode
      in multimode photonic band gap fibers.
AB  - We demonstrate the preparation and transmission of the lowest loss azimuthally
      polarized TE01- like mode in a photonic band gap (PBG) fiber. Using the nature of
      the mode and the properties of the band gap structure we construct a novel
      coupler that operates away from the band gap's center to enhance the differential
      losses and facilitate the radiative loss of hybrid fundamental fiber modes.
      Remarkably, even though the coupler is highly multimoded, a pure azimuthally
      polarized mode is generated after only 17 cm. Theoretical calculations verify the
      validity of this technique and accurately predict the coupling efficiency. The
      generation and single mode propagation of this unique azimuthally polarized,
      doughnut shaped mode in a large hollow-core fiber can find numerous applications
      including in optical microscopy, optical tweezers, and guiding particles along
      the fiber.

PMID- 22418481
TI  - Enhanced light output of InGaN/GaN blue light emitting diodes with Ag nano
      particles embedded in nano-needle layer.
AB  - 2.7 times increase in room temperature photoluminescence (PL) intensity and 3.2
      times increase in electroluminescence (EL) intensity were observed in blue multi
      quantum-well (MQW) GaN/InGaN light emitting diodes (LEDs) as a result of
      introduction of nano-needle structure embedded with Ag nanoparticles (NPs) into n
      GaN film underlying the active MQW region and thick p-GaN contact layer of LEDs.
      The nano-needle structure was produced by photoelectrochemical etching.
      Simultaneously a measurable decrease in room temperature decay time from 2.2 ns
      in control samples to 1.6 ns in PL was observed. The results are explained by
      strong coupling of recombination in GaN/InGaN MQWs with Ag NPs related localized
      surface plasmons.

PMID- 22418482
TI  - Superresolution four-wave mixing microscopy.
AB  - We report on the development of a superresolution four-wave mixing microscope
      with spatial resolution approaching 130 nm which represents better than twice the
      diffraction limit at 800 nm while retaining the ability to acquire materials- and
      chemical- specific contrast. The resolution enhancement is achieved by narrowing
      the microscope's excitation volume in the focal plane through the combined use of
      a Toraldo-style pupil phase filter with the multiplicative nature of four-wave
      mixing.

PMID- 22418483
TI  - Enhanced non-volatile and updatable holography using a polymer composite system.
AB  - Updatable holography is considered as the ultimate technique for true 3D
      information recording and display. However, there is no practical solution to
      preserve the required features of both non-volatility and reversibility which
      conflict with each other when the reading has the same wavelength as the
      recording. We demonstrate a non-volatile and updatable holographic approach by
      exploiting new features of molecular transformations in a polymer recording
      system. In addition, by using a new composite recording film containing photo
      reconfigurable liquid-crystal (LC) polymer, the holographic recording is enhanced
      due to the collective reorientation of LC molecules around the reconfigured
      polymer chains.

PMID- 22418484
TI  - Trapping metallic Rayleigh particles with radial polarization: reply to comment.
AB  - This is a reply to the comment by Iglesias and Saenz directed to a previous paper
      "Trapping metallic Rayleigh particles with radial polarization," by Q. Zhan, Opt.
      Express 12, 3377 (2004).

PMID- 22418485
TI  - All-optical tunability of microdisk lasers via photo-adressable polyelectrolyte
      functionalization.
AB  - Photoactive materials are highly promising candidates for novel applications as
      they enable all-optical control of photonic devices. Photochromic molecules
      exhibit a reversible change of their dielectric function upon irradiation with
      light of proper wavelength. The trans- and cis-isomers of azobenzene exhibit
      different absorption properties due to the effect of the configuration on the
      polarizability of the molecule. Here, we introduce a novel
      molecular/semiconductor hybrid device which is fully tunable by all-optical means
      via the integration of a semiconductor microdisk into a photo-adressable
      polyelectrolyte material. We demonstrate that such polyelectrolyte superlattices
      can be used to tune semiconductor photonic resonators with high precision and
      without any significant degeneration of device performance. Moreover, we
      demonstrate an all-optically tunable laser based on this hybrid concept.

PMID- 22418486
TI  - THz bandwidth optical switching with carbon nanotube metamaterial.
AB  - We provide the first demonstration of exceptional light-with-light optical
      switching performance of a carbon nanotube metamaterial - a hybrid nanostructure
      of a plasmonic metamaterial with semiconducting single-walled carbon nanotubes. A
      modulation depth of 10% in the near-IR with sub-500 fs response time is achieved
      with a pump fluence of just 10 MUJ/cm2, which is an order of magnitude lower than
      in previously reported artificial nanostructures. The improved switching
      characteristics of the carbon nanotube metamaterial are defined by an excitonic
      nonlinearity of carbon nanotubes resonantly enhanced by a concentration of local
      fields in the metamaterial. Since the spectral position of the excitonic response
      and metamaterial plasmonic resonance can be adjusted by using carbon nanotubes of
      different diameter and scaling of the metamaterial design, the giant nonlinear
      response of the hybrid metamaterial - in principle - can be engineered to cover
      the entire second and third telecom windows, from O- to U-band.

PMID- 22418487
TI  - Spectroscopic properties and laser performance of resonantly-pumped cryo-cooled
      Er3+:GdVO4.
AB  - We report a highly efficient cryo-cooled eye-safe laser operation of a resonantly
      pumped (in-band) Er3+:GdVO4 single crystal. The maximum continuous wave (CW)
      power of 10.3 W with 84% slope efficiency was achieved at 1598.7 with pumping at
      1538.6 nm by a spectrally-narrowed Er-fiber laser. Under the 1529 nm resonant
      pumping by a commercially available diode bar stack operating in a quasi-CW (QCW)
      mode, the laser delivered 37 W of output power with 68% slope efficiency. This is
      believed to be the first reported cryo-cooled Er3+:GdVO4 laser, resonantly-pumped
      into the 4I15/2 ->4I13/2 transition.

PMID- 22418488
TI  - Design of panoramic stereo imaging with single optical system.
AB  - A novel panoramic stereo imaging system with double panoramic annular lenses
      (PAL) is introduced in this paper. The proposed system consists of two coaxial
      PAL units and images on one sensor. The imaging rings are concentric. The object
      position can be calculated by triangulation. The novelty of this system is that
      the central blind zone of one PAL unit is partly used by the other as an image
      zone. The stereo field of view is 60 degrees ~105 degrees  * 360 degrees . The
      depth extracting resolution is about 500 mm at 1line/cm. The F# of the system is
      about 3, facilitating the system to be applied in low illumination environment. A
      design is presented and the depth extracting precision is analyzed.

PMID- 22418489
TI  - CMOS image sensor integrated with micro-LED and multielectrode arrays for the
      patterned photostimulation and multichannel recording of neuronal tissue.
AB  - We developed a complementary metal oxide semiconductor (CMOS) integrated device
      for optogenetic applications. This device can interface via neuronal tissue with
      three functional modalities: imaging, optical stimulation and electrical
      recording. The CMOS image sensor was fabricated on 0.35 MUm standard CMOS process
      with built-in control circuits for an on-chip blue light-emitting diode (LED)
      array. The effective imaging area was 2.0 * 1.8 mm2. The pixel array was composed
      of 7.5 * 7.5 MUm2 3-transistor active pixel sensors (APSs). The LED array had 10
      * 8 micro-LEDs measuring 192 * 225 MUm2. We integrated the device with a
      commercial multichannel recording system to make electrical recordings.

PMID- 22418490
TI  - Optical coherence tomography for whole eye segment imaging.
AB  - We proposed a dual focus dual channel spectral domain optical coherence
      tomography (SD-OCT) for simultaneous imaging of the whole eye segments from
      cornea to the retina. By using dual channels the system solved the problem of
      limited imaging depth of SD-OCT. By using dual focus the system solved the
      problem of simultaneous light focusing on the anterior segment of the eye and the
      retina. Dual focusing was achieved by adjusting the collimating lenses so the
      divergence of the two probing beams was tuned to make them focused at different
      depth in the eye. We further achieved full range complex (FRC) SD-OCT in one
      channel to increase the depth range for anterior segment imaging. The system was
      successfully tested by imaging a human eye in vivo.

PMID- 22418491
TI  - Terahertz band gaps induced by metal grooves inside parallel-plate waveguides.
AB  - We report experimental and finite-difference time-domain simulation studies on
      terahertz (THz) characteristics of band gaps by using metal grooves which are
      located inside the flare parallel-plate waveguide. The vertically localized
      standing-wave cavity mode (SWCM) between the upper waveguide surface and groove
      bottom, and the horizontally localized SWCM between two groove side walls (groove
      cavity) are observed. The E field intensity of the horizontally localized SWCM in
      grooves is very strongly enchanced which is three order higher than that of the
      input THz. The 4 band gaps except the Bragg band gap are caused by the pi radian
      delay (out of phase) between the reflected THz field by grooves and the
      propagated THz field through the air gap. The measurement and simulation results
      agree well.

PMID- 22418492
TI  - Directional coupling in channel plasmon-polariton waveguides.
AB  - We investigate directional couplers (DCs) formed by channel plasmon-polariton
      (CPP) waveguides (CPPWs). DCs comprising 5-um-offset S-bends and 40-um-long
      parallel CPPWs with different separations (0.08, 0.25, 0.5 and 2 um) between V
      groove channels are fabricated by using a focused ion-beam (FIB) technique in a 2
      MUm-thick gold film and characterized at telecom wavelengths (1425-1630 nm) with
      near-field optical microscopy. Experimental results reveal strong coupling,
      resulting in approximately equal power splitting between DC-CPPWs, for small CPPW
      separations (0.08 and 0.25 um). The coupling gradually deteriorates with the
      increase of separation between V-grooves and practically vanishes for the
      separation of 2 um. The DC-CPPW characteristics observed are found in good
      agreement with finite-element method (implemented in COMSOL) simulations.

PMID- 22418493
TI  - Surface-structured diffuser by iterative down-size molding with glass sintering
      technology.
AB  - In this paper, a down-size sintering scheme for making high-performance diffusers
      with micro structure to perform beam shaping is presented and demonstrated. By
      using down-size sintering method, a surface-structure film is designed and
      fabricated to verify the feasibility of the sintering technology, in which up to
      1/8 dimension reduction has been achieved. Besides, a special impressing
      technology has been applied to fabricate diffuser film with various materials and
      the transmission efficiency is as high as 85% and above. By introducing the
      diffuser into possible lighting applications, the diffusers have been shown high
      performance in glare reduction, beam shaping and energy saving.

PMID- 22418494
TI  - Composite chiral metamaterials with negative refractive index and high values of
      the figure of merit.
AB  - A composite chiral metamaterial (CCMM) is designed and studied both numerically
      and experimentally. The CCMM is constructed by the combination of a continuous
      metallic wires structure and a purely chiral metamaterial (CMM) that consists of
      conjugated Rosettes. For the CMM, only very small, useful bands of negative index
      can be obtained for circularly polarized waves. These bands are all above the
      chiral resonance frequencies because of the high value of the effective parameter
      of relative permittivity epsilon. After the addition of the continuous metallic
      wires, which provide negative permittivity, the high value of epsilon can be
      partially compensated. Thus, a negative index band for the left circularly
      polarized wave that is below the chiral resonance frequency is obtained for the
      CCMM. At the same time, a negative index band for the right circularly polarized
      wave that is above the chiral resonance frequency is also obtained. Furthermore,
      both negative index bands correspond to the transmission peaks and have high
      values of the figure of merit. Therefore, the CCMM design that is proposed here
      is more suitable than the CMM for the construction of chiral metamaterials with a
      negative index.

PMID- 22418495
TI  - Tunable and reconfigurable multi-tap microwave photonic filter based on dynamic
      Brillouin gratings in fibers.
AB  - We propose and experimentally demonstrate new architectures to realize multi-tap
      microwave photonic filters, based on the generation of a single or multiple
      dynamic Brillouin gratings in polarization maintaining fibers. The spectral range
      and selectivity of the proposed periodic filters is extensively tunable, simply
      by reconfiguring the positions and the number of dynamic gratings along the fiber
      respectively. In this paper, we present a complete analysis of three different
      configurations comprising a microwave photonic filter implementation: a simple
      notch-type Mach-Zehnder approach with a single movable dynamic grating, a multi
      tap performance based on multiple dynamic gratings and finally a stationary
      grating configuration based on the phase modulation of two counter-propagating
      optical waves by a common pseudo-random bit sequence (PRBS).

PMID- 22418496
TI  - High-speed low-voltage single-drive push-pull silicon Mach-Zehnder modulators.
AB  - We demonstrate a single-drive push-pull silicon Mach-Zehnder modulator (MZM) with
      a pi-phase-shift voltage of 3.1 V and speed up to 30 Gb/s. The on-chip insertion
      loss is 9 dB due to the use of a 6 mm-long phase shifter. Higher switching speed
      up to 40-50 Gb/s is also demonstrated in devices with shorter phase shifters
      which require higher drive voltages but have lower insertion losses.

PMID- 22418497
TI  - Efficient waveguide mode extraction in white organic light emitting diodes using
      ITO-anodes with integrated MgF2-columns.
AB  - We report a simple approach to enhance the out-coupling efficiency in white
      organic light emitting diodes (WOLEDs). By incorporating MgF2-columns into the
      ITO-anode and optimizing of their geometry, an overall efficiency enhancement of
      up to 38% is achieved. In addition, the structuring of the anode does not lead to
      a change in the electrical behaviour of the devices. As evidenced by goniometric
      measurements, the angular emission characteristics of the WOLEDs remain
      unchanged. Simulations, performed with the T-matrix method, reveal the effect of
      the enhanced outcoupling efficiency of this approach.

PMID- 22418498
TI  - Rigorous theory on elliptical mirror focusing for point scanning microscopy.
AB  - A rigorous elliptical mirror focusing formula based on spherical wave
      transformation is derived as a kind of imaging technique with high NA for
      potential applications in molecule imaging, spectroscopy and industrial artifact
      microscopy. An apodization factor is given and used to compare the energy
      conversation rules in lens transmission and parabolic and elliptical mirror
      reflections. Simulation results indicate that the axial HFWHM of elliptical and
      parabolic mirrors is about 80% of the corresponding HFWHM of lens in case of NA =
      1 and phis = 0, and the side lobe noise is also slightly lower than that of lens,
      but the transverse HFWHM of mirrors is comparatively wider despite the width of
      main lobe is still smaller. In comparison with parabolic mirror based system, an
      elliptical mirror based system is potentially promising in aberration control of
      incident beam when the aperture of mirror is enlarged to adapt a large stage or
      specimen container at a small beam shading ratio.

PMID- 22418499
TI  - Extreme ultraviolet light source based on intracavity high harmonic generation in
      a mode locked Ti:sapphire oscillator with 9.4 MHz repetition rate.
AB  - We report on the realization of an intracavity high harmonic source with a cutoff
      above 30 eV. The EUV source is based on a high power, hard-aperture, Kerr-lens
      mode-locked Ti:sapphire oscillator with a repetition rate of 9.4 MHz. The laser
      is operated in the net negative dispersion regime resulting in intracavity pulses
      as short as 17 fs with 1 uJ pulse energy. In a second intracavity focus,
      intensity more than 1014 W/cm2 has been achieved, which is sufficient for high
      harmonic generation in a Xenon gas jet.

PMID- 22418500
TI  - Wavelength and bandwidth tunable photonic stopband of ferroelectric liquid
      crystals.
AB  - The chiral smectic C phase of ferroelectric liquid crystals (FLCs) has a self
      assembling helical structure which is regarded as a one-dimensional pseudo
      photonic crystal. It is well known that a stopband of a FLC can be tuned in
      wavelength domain by changing temperature or electric field. We here have
      demonstrated an FLC stopband with independently tunable wavelength and bandwidth
      by controlling temperature and incident angle. At highly oblique incidence, the
      stopband does not have polarization dependence. Furthermore, the bandwidth at
      highly oblique incidence is much wider than that at normal incidence. The
      mechanism of the tunable stopband is clarified by considering the reflection at
      oblique incidence.

PMID- 22418501
TI  - Terahertz probe for spectroscopy of sub-wavelength objects.
AB  - A system of two probes is designed for terahertz (THz) time-domain spectroscopy
      of sub-wavelength size objects. A twin-needle probe confines broadband THz pulses
      spatially by means of surface plasmon waves to a sub-wavelength spot smaller than
      10 microns. The confined pulses are detected within the near-field zone of the
      twin-needle probe by a sub-wavelength aperture probe. The system allows THz
      spectroscopy to be applied to single micrometer-size objects in the 1-2.5THz
      region.

PMID- 22418503
TI  - Four-wave-mixing between the upper excited states in a ladder-type atomic
      configuration.
AB  - Four-wave-mixing (FWM) radiation is generated between the hyperfine structures of
      the 5D and 5P states in a thermally broadened rubidium atomic vapor using
      resonant atomic coherence. Background-free unidirectional signals having narrow
      spectral linewidths are isolated and experimentally studied in the frequency
      domain, and the effects of the driving beam parameters on the properties of the
      radiation are discussed. The radiation has several new properties compared to
      traditional FWM radiations generated between the 5P and 5S states. The high
      resolution signals obtained in this method could make it favorable in
      spectroscopic procedures that rely on two-photon fluorescence.

PMID- 22418504
TI  - Gain recovery in a quantum dot semiconductor optical amplifier and corresponding
      pattern effects in amplified optical signals at 1.5 MUm.
AB  - Fast gain recovery observed in quantum-dot semiconductor-optical-amplifiers
      (QDSOAs) is useful for amplifying high-speed optical signals. The small but
      finite slow recovery component can deteriorate the signal amplification due to
      the accumulation of gain saturation during 10 Gb/s operation. A study of the gain
      recoveries and pattern effects in signals amplified using a 1.5 MUm InAs/InGaAsP
      QDSOA reveals that the gain recovery is always fast, and pattern-effect-free
      amplification is observed at the ground state. However, at the excited state, the
      slow component increases with the current, and significant pattern effects are
      observed. Simulations of the pattern effects agreed with the observed
      experimental trends.

PMID- 22418505
TI  - Large lateral photovoltaic effects in Co/Alq3 granular films on Si substrates.
AB  - A series of Co/Alq3 granular films were deposited on silicon substrates using co
      evaporation technique. Under the nonuniform illumination of a laser beam, lateral
      photovoltaic effect (LPE) was observed in the samples, with the optimal open
      circuit position sensitivity of 34.7 mV/mm. The insertion of oxide layer results
      in the decrease of lateral photovoltage (LPV) and the irreversible LPE. The
      dependence of lateral photovoltaic effect on substrates was also briefly
      investigated. The possible mechanism was discussed.

PMID- 22418506
TI  - Experimental demonstration of novel source-free ONUs in bidirectional RF up
      converted optical OFDM-PON utilizing polarization multiplexing.
AB  - We propose and experimentally demonstrate a novel cost-effective optical
      orthogonal frequency-division multiplexing-based passive optical network (OFDM
      PON) system, wherein all optical network units (ONUs) are source-free not only in
      the optical domain but also in the electric domain, by utilizing polarization
      multiplexing (PolMUX) in the downlink transmission. Two pure optical bands with a
      frequency interval of 10 GHz and downlink up-converted 10 GHz OFDM signal are
      carried in two orthogonal states of polarization (SOPs), respectively. 10 GHz
      radio frequency (RF) source can be generated by a heterodyne of two pure optical
      bands after polarization beam splitting in each ONU, therefore it can be used to
      down-convert the downlink OFDM signal and up-convert the uplink OFDM signal. In
      the whole bidirectional up-converted OFDM-PON system, only one single RF source
      is employed in the optical line terminal (OLT). Experimental results successfully
      verify the feasibility of our proposed cost-effective optical OFDM-PON system.

PMID- 22418507
TI  - Quasi-phase-matching high harmonic generation using trains of pulses produced
      using an array of birefringent plates.
AB  - Quasi-phase-matched high harmonic generation using trains of up to 8 counter
      propagating pulses is explored. For trains of up to 4 pulses the measured
      enhancement of the harmonic signal scales with the number of pulses N as (N +
      1)2, as expected. However, for trains with N > 4, no further enhancement of the
      harmonic signal is observed. This effect is ascribed to changes of the coherence
      length Lc within the generating medium. Techniques for overcoming the variation
      of Lc are discussed. The pressure dependence of quasi-phase-matching is
      investigated and the switch from true-phase-matching to quasi-phase-matching is
      observed.

PMID- 22418508
TI  - Bredigite-structure orthosilicate phosphor as a green component for white LED:
      the structural and optical properties.
AB  - A green-emitting phosphor, Ca14-xEuxMg2[SiO4]8 (CMS:Eu2+), has been synthesized
      as a component of white light emitting diodes (WLEDs). The emission spectrum is
      broad, with a maximum at about 505 nm under 400 nm excitation due to the
      transition from the 4f65d excited state to the 4f7-ground state of a Eu2+ ion.
      The dipole-dipole interaction was a dominant energy transfer mechanism of the
      electric multipolar character of CMS:Eu2+. The critical distance was calculated
      as 12.9 A and 14.9 A using a critical concentration of Eu2+ and Dexter's theory
      for energy transfer. When CMS:Eu2+ and red phosphor are incorporated with an
      encapsulant on an ultraviolet (lambdamax = 395 nm) light emitting diodes (LEDs),
      white light with a color rendering index of 91 under a forward bias current of 20
      mA was obtained. The structural and optical characterization of the phosphor is
      described.

PMID- 22418509
TI  - First principles study of the ternary complex model of EL2 defect in GaAs
      saturable absorber.
AB  - First principles calculations are performed for the perfect GaAs crystal, the
      double Ga vacancies (VGa)2, and the ternary complex defect (AsGaVAsVGa), using
      the state-of-the-art computational method with the Heyd-Scuseria-Ernzerhof (HSE)
      hybrid functional to correct the band gap and account for a proper description of
      the interaction between defects states and bulk states. Three shallow acceptor
      defect levels are found due to the creation of (VGa)2 with nearest-neighbor As
      dangling bonds. However, for GaAs with the ternary complex defects (AsGaVAsVGa),
      the As antisite AsGa and the VAs'S nearest-neighbor Ga dangling bonds provoke
      several donor defect states. The lowest donor defect state locates at 0.85 eV
      below the bottom of conduction band, which is very close to the experimental
      observation of the EL2 defect level. In addition, structual evolution from (VGa)2
      defect to the ternary defect complex (AsGaVAsVGa) is simulated by ab initio
      molecular dynamic (MD) calculation at different temperatures. The MD results
      demonstrate that the ternary complex defect (AsGaVAsVGa) can be converted from
      the double Ga vacancies (VGa)2 at room temperature, and it can exist stably at
      higher temperature. The present work is helpful to unravel the microstructure and
      the forming mechanism of the EL2 defect, to find out methods to improve the
      performance of the GaAs saturable absorber by changing the growth conditions of
      GaAs crystal.

PMID- 22418510
TI  - Source localization approach for functional DOT using MUSIC and FDR control.
AB  - In this paper, we formulate diffuse optical tomography (DOT) problems as a source
      localization problem and propose a MUltiple SIgnal Classification (MUSIC)
      algorithm for functional brain imaging application. By providing MUSIC spectra
      for major chromophores such as oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbR),
      we are able to investigate the spatial distribution of brain activities.
      Moreover, the false discovery rate (FDR) algorithm can be applied to control the
      family-wise error in the MUSIC spectra. The minimum distance between the center
      of mass in DOT and the Montreal Neurological Institute (MNI) coordinates of
      target regions in experiments was between approximately 6 and 18 mm, and the
      displacement of the center of mass in DOT and fMRI ranged between 12 and 28 mm,
      which demonstrate the legitimacy of the DOT-based imaging. The proposed brain
      mapping method revealed its potential as an alternative algorithm to monitor the
      brain activation.

PMID- 22418511
TI  - Self-mixing in multi-transverse mode semiconductor lasers: model and potential
      application to multi-parametric sensing.
AB  - A general model is proposed for a Vertical Cavity Surface Emitting Laser (VCSEL)
      with medium aspect ratio whose field profile can be described by a limited set of
      Gauss-Laguerre modes. The model is adapted to self-mixing schemes by supposing
      that the output beam is reinjected into the laser cavity by an external target
      mirror. We show that the self-mixing interferometric signal exhibits features
      peculiar of the spatial distribution of the emitted field and the target
      reflected field and we suggest an applicative scheme that could be exploited for
      experimental displacement measurements. In particular, regimes of transverse mode
      locking are found, where we propose an operational scheme for a sensor that can
      be used to simultaneously measure independent components of the target
      displacement like target translations along the optical axis (longitudinal axis)
      and target rotations in a plane orthogonal to the optical axis (transverse
      plane).

PMID- 22418512
TI  - Reflectivity and polarization dependence of polysilicon single-film broadband
      photonic crystal micro-mirrors.
AB  - We report on the fabrication of 2-D photonic crystal (PC) micro-mirrors, and
      Finite Difference Time Domain (FDTD) simulations and measurements of their
      reflectance spectra and polarization dependence at normal incidence. The PC
      mirrors were fabricated in free-standing thin polysilicon membranes supported by
      silicon nitride films for stress compensation. Greater than 90% reflectivity is
      measured over a wavelength range of 35 nm from 1565 nm to 1600 nm with small
      polarization dependence. Our FDTD simulations show that fabrication errors on the
      order of tens of nanometers can strongly affect the reflection spectra. When the
      fabrication errors are kept below this level, FDTD simulations on perfectly
      periodic structures accurately predict the reflection spectra of the fabricated
      PC mirrors, despite their sensitivity to the fabrication errors.

PMID- 22418513
TI  - Periodic interactions between solitons and dispersive waves during the generation
      of non-coherent supercontinuum radiation.
AB  - We present a numerical study of interactions between dispersive waves (DWs) and
      solitons during supercontinuum generation in photonic crystal fibers pumped with
      picosecond laser pulses. We show how the soliton-induced trapping potential
      evolves along the fiber and affects the dynamics of a DW-soliton pair. Individual
      frequency components of the DW periodically interact with the soliton resulting
      in stepwise frequency blue shifts. In contrast, the ensemble blue shifts of all
      frequency components in the DW appear to be quasi-continuous. The step size of
      frequency up-conversion and the temporal separation between subsequent soliton-DW
      interactions are governed by the potential well which confines the soliton-DW
      pair and which changes in time.

PMID- 22418514
TI  - Compact MEMS-driven pyramidal polygon reflector for circumferential scanned
      endoscopic imaging probe.
AB  - A novel prototype of an electrothermal chevron-beam actuator based
      microelectromechanical systems (MEMS) platform has been successfully developed
      for circumferential scan. Microassembly technology is utilized to construct this
      platform, which consists of a MEMS chevron-beam type microactuator and a micro
      reflector. The proposed electrothermal microactuators with a two-stage
      electrothermal cascaded chevron-beam driving mechanism provide displacement
      amplification, thus enabling a highly reflective micro-pyramidal polygon
      reflector to rotate a large angle for light beam scanning. This MEMS platform is
      ultra-compact, supports circumferential imaging capability and is suitable for
      endoscopic optical coherence tomography (EOCT) applications, for example, for
      intravascular cancer detection.

PMID- 22418515
TI  - Plasmonic effects in amorphous silicon thin film solar cells with metal back
      contacts.
AB  - Plasmonic effects in amorphous silicon thin film solar cells with randomly
      textured metal back contact were investigated experimentally and numerically. The
      influence of different metal back contacts with and without ZnO interlayer was
      studied and losses in the individual layers of the solar cell were quantified.
      The amorphous silicon thin film solar cells were prepared on randomly textured
      substrates using large area production equipment and exhibit conversion
      efficiencies approaching 10%. The optical wave propagation within the solar cells
      was studied by Finite Difference Time Domain simulations. The quantum efficiency
      of solar cells with and without ZnO interlayer was simulated and the interplay
      between the reflection, quantum efficiency and absorption in the back contact
      will be discussed.

PMID- 22418516
TI  - Position-independent normal-mode splitting in cavities filled with zero-index
      metamaterials.
AB  - We study the normal-mode splitting when an oscillator is placed in a two
      dimensional photonic crystal microcavity embedded with an impedance-matched or an
      impedance-mismatched zero-index medium (ZIM). Because of the (nearly) uniform
      localized fields in the ZIM, the normal-mode splitting remains (almost) invariant
      no matter where the oscillator is. When a split ring resonator is coupled to a
      transmission-line- based effective ZIM at various locations, nearly position
      independent mode splitting is observed.

PMID- 22418517
TI  - Continuously tunable solution-processed organic semiconductor DFB lasers pumped
      by laser diode.
AB  - The fabrication and characterization of continuously tunable, solution-processed
      distributed feedback (DFB) lasers in the visible regime is reported. Continuous
      thin film thickness gradients were achieved by means of horizontal dipping of
      several conjugated polymer and blended small molecule solutions on cm-scale
      surface gratings of different periods. We report optically pumped continuously
      tunable laser emission of 13 nm in the blue, 16 nm in the green and 19 nm in the
      red spectral region on a single chip respectively. Tuning behavior can be
      described with the Bragg-equation and the measured thickness profile. The laser
      threshold is low enough that inexpensive laser diodes can be used as pump
      sources.

PMID- 22418518
TI  - Enhanced in and out-coupling of InGaAs slab waveguides by periodic metal slit
      arrays.
AB  - We studied the in- and the out-coupling efficiencies of photons with a thin
      InGaAs slab covered by periodic gold nano-slit arrays, by measuring transmission
      and photoluminescence (PL) spectra. While the maximum in-coupled photons into the
      InGaAs slab waveguide were found at dip positions in transmission spectra, the
      mostly out-coupled photons were observed as peaks in PL spectra. For different
      periods of slit arrays and incident angles we discussed spectral positions of
      transmission dips and efficiency of the in-coupling influenced by the absorption
      coefficient of InGaAs. In PL spectra we measured overall enhanced PL intensities
      from the InGaAs slab covered by slit arrays compared to that of a bare InGaAs,
      where the peak positions are determined by the period of slit arrays as well. Our
      findings are important for designing semiconductors both as an optically passive
      waveguide and active light emitter.

PMID- 22418519
TI  - On-chip coherent combining of angled-grating diode lasers toward bar-scale single
      mode lasers.
AB  - Single mode operation of broad-area diode lasers, which is the key to obtain high
      power, high brightness sources, is difficult due to highly nonlinear materials
      and strong coupling between gain and index. Conventional broad-area lasers
      usually operate with multiple modes and have poor beam quality. Laser bars
      usually consist of incoherently combined broad-area single emitters placed side
      by side. In this article, we have demonstrated a novel integrated laser
      architecture in which Bragg diffraction is used to realize simultaneous modal
      control and coherent combining of broad-area diode lasers. Our experimental
      results show that two 100 MUm wide, 1.3mm long InP broad-area lasers provide near
      diffraction-limited output beam and are coherently combined at the same time
      without any external optical components. Furthermore, our design can be expanded
      to a coherently combined broad-area laser array that turns a laser bar into a
      coherent single mode laser with diffraction-limited beam quality.

PMID- 22418520
TI  - Polarization dependence of Brillouin linewidth and peak frequency due to fiber
      inhomogeneity in single mode fiber and its impact on distributed fiber Brillouin
      sensing.
AB  - The dependence of Brillouin linewidth and peak frequency on lightwave state of
      polarization (SOP) due to fiber inhomogeneity in single mode fiber (SMF) is
      investigated by using Brillouin optical time domain analysis (BOTDA) system.
      Theoretical analysis shows fiber inhomogeneity leads to fiber birefringence and
      sound velocity variation, both of which can cause the broadening and asymmetry of
      the Brillouin gain spectrum (BGS) and thus contribute to the variation of
      Brillouin linewidth and peak frequency with lightwave SOP. Due to fiber
      inhomogeneity both in lateral profile and longitudinal direction, the measured
      BGS is the superposition of several spectrum components with different peak
      frequencies within the interaction length. When pump or probe SOP changes, both
      the peak Brillouin gain and the overlapping area of the optical and acoustic mode
      profile that determine the peak efficiency of each spectrum component vary within
      the interaction length, which further changes the linewidth and peak frequency of
      the superimposed BGS. The SOP dependence of Brillouin linewidth and peak
      frequency was experimentally demonstrated and quantified by measuring the
      spectrum asymmetric factor and fitting obtained effective peak frequency
      respectively via BOTDA system on standard step-index SMF-28 fiber. Experimental
      results show that on this fiber the Brillouin spectrum asymmetric factor and
      effective peak frequency vary in the range of 2% and 0.06MHz respectively over
      distance with orthogonal probe input SOPs. Experimental results also show that in
      distributed fiber Brillouin sensing, polarization scrambler (PS) can be used to
      reduce the SOP dependence of Brillouin linewidth and peak frequency caused by
      fiber inhomogeneity in lateral profile, however it maintains the effects caused
      by fiber inhomogeneity in longitudinal direction. In the case of non-ideal
      polarization scrambling using practical PS, the fluctuation of effective
      Brillouin peak frequency caused by fiber inhomogeneity provides another limit of
      sensing frequency resolution of distributed fiber Brillouin sensor.

PMID- 22418521
TI  - Spin-polarized dark state free CPT state preparation with co-propagating left and
      right circularly polarized lasers.
AB  - We have developed and experimentally studied a coherent population trapping (CPT)
      state preparation scheme for atomic clock application with co-propagating left
      and right circularly polarized lasers. With realization of constructive
      interference and spin-polarized dark state free in CPT state preparation, we have
      obtained CPT resonance signal 3 times larger than that of the conventional scheme
      used in atomic clock. Polarization fluctuations and CPT signal sensitivity to
      laser power behaviors are both improved with the scheme. Our study reveals that
      it is a promising candidate for both normal-size and chip-scale CPT atomic
      clocks.

PMID- 22418522
TI  - Dissipative soliton in actively mode-locked fiber laser.
AB  - A dissipative soliton in an all-normal-dispersion actively mode-locked ytterbium
      doped fiber laser is reported for the first time. Pulses with 10-ps duration and
      edge-to-edge bandwidth of 9 nm are generated, and then extra-cavity compressed
      down to 560 fs due to the large chirp. Widely wavelength tuning between 1031 and
      1080 nm is achieved by adjusting the driving frequency only. Our simulation shows
      that the proposed laser operates in the dissipative soliton shaping regime.

PMID- 22418523
TI  - Experimental characterization of the transfer function for a Silver-dielectric
      superlens.
AB  - We describe a technique for experimentally determining the spatial-frequency
      modulation transfer function for near-field super-resolution imaging systems and
      present such a modulation transfer function for a 20|40|20 nm poly(vinyl
      alcohol)~(PVA)|Silver|PVA superlens exposed to 365 nm wavelength (i-line)
      radiation through a 50-nm thick tungsten mask. An extensive spectral
      characterization is achieved from only two exposures, with transmission
      coefficients determined for spatial frequencies as high as 13 um-1, corresponding
      to lambda / 4.75. The resulting transfer function is in good agreement with
      analytical models that incorporate the effects of mask-superlens interactions.

PMID- 22418524
TI  - Multilayer mirrored bubbles with spatially-chirped and elastically-tuneable
      optical bandgaps.
AB  - We demonstrate the multifolding Origami manufacture of elastically-deformable
      Distributed Bragg Reflector (DBR) membranes that reversibly color-tune across the
      full visible spectrum without compromising their peak reflectance. Multilayer
      films composed of alternating transparent rubbers are fixed over a 300 MUm wide
      pinhole and deformed by pressure into a concave shape. Pressure-induced color
      tuning from the near-IR to the blue arises from both changes in thickness of the
      constituent layers and from tilting of the curved DBR surfaces. The layer
      thickness and color distribution upon deformation, the band-gap variation and the
      repeatability of cyclic color tuning, are mapped through micro-spectroscopy. Such
      spatially-dependent thinning of the film under elastic deformation produces
      spatial chirps in the color, and are shown to allow reconstruction of complex 3D
      strain distributions.

PMID- 22418525
TI  - Finite element modeling of bulk ultrasonic waves generated by ring-shaped laser
      illumination in a diamond anvil cell.
AB  - Thermoelastic finite element models are established to study the bulk ultrasonic
      waves of an aluminum film generated by ring-shaped laser illumination in a
      diamond anvil cell. By analyzing the amplitudes of bulk ultrasonic waves arrived
      at the rear surface of film in detail, it shows that there exists strong
      enhancement effects on the central axis of the ring due to the constructive
      interference among the waves created by different parts of the ring source. The
      displacement distributions along the central axis indicate that the focal depth
      of shear wave is mainly determined by its directivity induced by a point-like
      laser source in a DAC system while it is more complicated to determine the focal
      depth of longitudinal wave. In particular, through changing the ring radius, we
      quantitatively demonstrate that the signal amplitudes generated by a ring source
      are far greater than those generated by a point-like source.

PMID- 22418526
TI  - 512QAM Nyquist sinc-pulse transmission at 54 Gbit/s in an optical bandwidth of 3
      GHz.
AB  - We demonstrate for the first time transmission of 54 Gbit/s and 48 Gbit/s over 44
      km and 150 km, respectively, utilizing an optical bandwidth of only 3 GHz. We
      used polarization division multiplexed 512QAM and 256QAM modulation formats in
      combination with Nyquist pulse shaping having virtually zero roll-off. The
      resulting spectral efficiencies range up to 18 bit/s/Hz and 16 bit/s/Hz,
      respectively. Taking into account the overhead required for forward error
      correction, the occupied signal bandwidth corresponds to net spectral
      efficiencies of 14.4 bit/s/Hz and 15 bit/s/Hz, which could be achieved in a
      wavelength division multiplexed network without spectral guard bands.

PMID- 22418527
TI  - Enhancement of electro-optic properties in liquid crystal devices via titanium
      nanoparticle doping.
AB  - We investigated the properties of nematic liquid crystal device (NLC) doped with
      titanium (Ti) nanoparticle (~100nm). The electro-optic (EO) properties of LCs
      changed according to Ti nanoparticle doping concentration. Ti nanoparticles in
      the NLC cells focused the electric field flux and strengthened the electric
      field. Further, Ti nanoparticles in NLC molecules may trap charged ionic
      impurities and suppress the screen effect, leading to a stronger electric field
      and the van der Waals dispersion interactions between NLC molecules and the
      alignment layers. We also simulated the boundary conditions of the Ti
      nanoparticles in the electric field using Ansoft Maxwell software. Our
      experimental results agreed with the phenomenon predicted by software simulation
      based on general physical theory. Synthetically, at a 1.0 wt. % Ti nanoparticle
      doping concentration, the NLC cells showed the best EO properties, such as a low
      threshold voltage (1.25V), fast response time (13.2ms), and low pretilt angle
      (3.90 degrees ).

PMID- 22418528
TI  - General analysis of the mode interaction in multimode active fiber.
AB  - General analysis of the mode interaction in multimode fiber is presented in this
      paper. By taking local gain into consideration, the general coupled mode
      equations in multimode active fiber are deduced in the model and the effect of
      various factors can be analyzed based on the general coupled mode equations.
      Analytical expression of the beam quality factor is deduced for the optical field
      emerging from the multimode active fiber. The evolution of the mode power and M2
      factor along the fiber are analyzed by numerical evaluations.

PMID- 22418529
TI  - Teardrop-shaped surface-plasmon resonators.
AB  - A new surface plasmon resonator, in the form of a metal cylinder shaped like a
      teardrop, is proposed and modeled using hypersingular integral equations.
      Illuminating the apex of the teardrop along its axis of symmetry with TM
      polarised light excites equal-magnitude surface plasmons counter-propagating
      around its periphery. Interference of these counter-propagating surface plasmons
      leads to resonant modes having very sharp line-widths (~0.6 nm) and large quality
      factors (~3400). In water, a Au teardrop supports resonant modes having large
      bulk sensitivities (~1900 nm/RIU) and remarkably large figures-of-merit (~1700),
      about 1000 * larger than the figure-of-merit of, e.g., isolated Au nano-spheres.
      The scattering cross-section of the structure near resonant modes exhibits a Fano
      like line-shape. The teardrop should find applications as a high-quality surface
      plasmon resonator or as a biosensing element.

PMID- 22418530
TI  - Coherent anti-Stokes Raman scattering with broadband excitation and narrowband
      probe.
AB  - An improved CARS setup based on noncollinear optical parametric amplifiers
      (NOPAs) is presented which combines broad tunability and a wide excitation
      bandwidth with good spectral and temporal resolution. Picosecond Raman pump and
      probe pulses are generated by a modified narrowband NOPA. Combining them with sub
      50 fs Stokes pulses results in highly time resolved CARS spectra with line widths
      down to 20 cm-1. The determination of a vibrational decoherence time is
      demonstrated for chloroform. Beating phenomena in case of overlapping Raman bands
      and an increase of spectral structure for coalescing bands are observed for
      cyclohexane and an ionic liquid respectively.

PMID- 22418531
TI  - Wavelength conversion and unicast of 10-Gb/s data spanning up to 700 nm using a
      silicon nanowaveguide.
AB  - We report extremely large probe-idler separation wavelength conversion (545 nm)
      and unicast (700 nm) of 10-Gb/s data signals using a dispersion-engineered
      silicon nanowaveguide. Dispersion-engineered phase matching in the device
      provides a continuous four-wave-mixing efficiency 3-dB bandwidth exceeding 800
      nm. We report the first data validation of wavelength conversion (data modulated
      probe) and unicast (data modulated pump) of 10-Gb/s data with probe-idler
      separations spanning 60 nm up to 700 nm accompanied with sensitivity gain in a
      single device. These demonstrations further validate the silicon platform as a
      highly broadband flexible platform for nonlinear all-optical data manipulation.

PMID- 22418532
TI  - Phase contrast laminography based on Talbot interferometry.
AB  - Synchrotron laminography is combined with Talbot grating interferometry to
      address weakly absorbing specimens. Integrating both methods into one set-up
      provides a powerful x-ray diagnostical technique for multiple contrast screening
      of macroscopically large flat specimen and a subsequent non-destructive three
      dimensional (3-D) inspection of regions of interest. The technique simultaneously
      yields the reconstruction of the 3-D absorption, phase, and the so-called dark
      field contrast maps. We report on the theoretical and instrumental implementation
      of of this novel technique. Its broad application potential is exemplarily
      demonstrated for the field of cultural heritage, namely study of the historical
      Dead Sea parchment.

PMID- 22418533
TI  - High-efficiency terahertz pulse generation via optical rectification by
      suppressing stimulated Raman scattering process.
AB  - We experimentally demonstrate high-efficiency terahertz pulse generation via
      optical rectification in LiNbO3. The spectral broadening of an excitation pulse
      via the stimulated Raman scattering process coincides with high-efficiency
      terahertz pulse generation, which enhances undesired stretching of the excitation
      pulse owing to the very high group velocity dispersion in LiNbO3. We avoid this
      by the bandwidth control of the excitation pulse and achieve the highest reported
      efficiency of 0.21% for energy conversion into a THz pulse.

PMID- 22418534
TI  - Performance analysis of coherent wireless optical communications with atmospheric
      turbulence.
AB  - Coherent wireless optical communication systems with heterodyne detection are
      analyzed for binary phase-shift keying (BPSK), differential PSK (DPSK), and M-ary
      PSK over Gamma-Gamma turbulence channels. Closed-form error rate expressions are
      derived using a series expansion approach. It is shown that, in the special case
      of K-distributed turbulence channel, the DPSK incurs a 3 dB signal-to-noise ratio
      (SNR) penalty compared to BPSK in the large SNR regime. The outage probability is
      also obtained, and a detailed outage truncation error analysis is presented and
      used to assess the accuracy in system performance estimation. It is shown that
      our series error rate expressions are simple to use and highly accurate for
      practical system performance estimation.

PMID- 22418535
TI  - Slot antenna as a bound charge oscillator.
AB  - We study the scattering properties of an optical slot antenna formed from a
      narrow rectangular hole in a metal film. We show that slot antennas can be
      modeled as bound charge oscillators mediating resonant light scattering. A simple
      closed-form expression for the scattering spectrum of a slot antenna is obtained
      that reveals the nature of a bound charge oscillator and also the effect of a
      substrate. We find that the spectral width of scattering resonance is dominated
      by a radiative damping caused by the Abraham-Lorentz force acting on a bound
      charge. The bound charge oscillator model provides not only an intuitive physical
      picture for the scattering of an optical slot antenna but also reasonable
      numerical agreements with rigorous calculations using the finite-difference time
      domain method.

PMID- 22418536
TI  - Effect of depth dependent spherical aberrations in 3D structured illumination
      microscopy.
AB  - We model the effect of depth dependent spherical aberration caused by a
      refractive index mismatch between the mounting and immersion mediums in a 3D
      structured illumination microscope (SIM). We first derive a forward model that
      takes into account the effect of the depth varying aberrations on both the
      illumination and the detection processes. From the model, we demonstrate that
      depth dependent spherical aberration leads to loss of signal only due to its
      effect on the detection response of the system, while its effect on illumination
      leads to phase shifts between orders that can be handled computationally in the
      reconstruction process. Further, by using the model, we provide guidelines for
      optical corrections of aberrations with different complexities, and explain how
      the proposed corrections simplify the forward model. Finally, we show that it is
      possible to correct both illumination and detection aberrations using a
      deformable mirror only on the detection path of the microscope.

PMID- 22418537
TI  - Semi-Huber potential function for image segmentation.
AB  - In this work, a novel model of Markov Random Field (MRF) is introduced. Such a
      model is based on a proposed Semi-Huber potential function and it is applied
      successfully to image segmentation in presence of noise. The main difference with
      respect to other half-quadratic models that have been taken as a reference is,
      that the number of parameters to be tuned in the proposed model is smaller and
      simpler. The idea is then, to choose adequate parameter values heuristically for
      a good segmentation of the image. In that sense, some experimental results show
      that the proposed model allows an easier parameter adjustment with reasonable
      computation times.

PMID- 22418538
TI  - A high resolution optical vector network analyzer based on a wideband and
      wavelength-tunable optical single-sideband modulator.
AB  - A high resolution optical vector network analyzer (OVNA) implemented based on a
      wideband and wavelength-tunable optical single-sideband (OSSB) modulator is
      proposed and experimentally demonstrated. The OSSB modulation is achieved using a
      phase modulator and a tunable optical filter with a passband having two steep
      edges and a flat top. Wideband and wavelength-tunable OSSB modulation is
      achieved. The incorporation of the OSSB modulator into the OVNA is experimentally
      evaluated. The measurement of the magnitude and phase response of an ultra-narrow
      band fiber Bragg grating (FBG) and that of the stimulated Brillouin scattering
      (SBS) in a single-mode fiber is performed. A measurement resolution as high as 78
      kHz is achieved.

PMID- 22418539
TI  - Depth measurements through controlled aberrations of projected patterns.
AB  - Three-dimensional displays have become increasingly present in consumer markets.
      However, the ability to capture three-dimensional images in space confined
      environments and without major modifications to current cameras is uncommon. Our
      goal is to create a simple modification to a conventional camera that allows for
      three dimensional reconstruction. We require such an imaging system have imaging
      and illumination paths coincident. Furthermore, we require that any three
      dimensional modification to a camera also permits full resolution 2D image
      capture.Here we present a method of extracting depth information with a single
      camera and aberrated projected pattern. A commercial digital camera is used in
      conjunction with a projector system with astigmatic focus to capture images of a
      scene. By using an astigmatic projected pattern we can create two different focus
      depths for horizontal and vertical features of a projected pattern, thereby
      encoding depth. By designing an aberrated projected pattern, we are able to
      exploit this differential focus in post-processing designed to exploit the
      projected pattern and optical system. We are able to correlate the distance of an
      object at a particular transverse position from the camera to ratios of
      particular wavelet coefficients.We present our information regarding
      construction, calibration, and images produced by this system. The nature of
      linking a projected pattern design and image processing algorithms will be
      discussed.

PMID- 22418540
TI  - Mode profile imaging and loss measurement for uniform and tapered single-mode 3D
      waveguides in diffusive photopolymer.
AB  - We demonstrate single-mode uniform and parabolically tapered three-dimensional
      waveguides fabricated via direct-write lithography in diffusion-based
      photopolymers. Modulation of the writing power is shown to compensate Beer
      Lambert absorption in the single-photon initiator and to provide precise control
      of modal tapers. A laminated sample preparation is introduced to enable full 3D
      characterization of these modal tapers without the need for sample polishing
      which is difficult for this class of polymer. The accuracy and repeatability of
      this modal characterization is shown to allow precise measurement of propagation
      loss from single samples. These testing procedures are used to demonstrate single
      mode waveguides with 0.147 dB/cm excess propagation loss and symmetrical tapers
      up to 1:2.5 using 1.5 microwatts of continuous write power.

PMID- 22418541
TI  - Theory and modeling of electrically tunable metamaterial devices using inter
      subband transitions in semiconductor quantum wells.
AB  - In this paper, we propose a new and versatile mechanism for electrical tuning of
      planar metamaterials: strong coupling of metamaterial resonances to engineered
      intersubband transitions that can be tuned through the application of an
      electrical bias. We present the general formalism that allows calculating the
      permittivity tensor for intersubband transitions in generic semiconductor
      heterostructures and we study numerically the specific case of coupling and
      tuning metamaterials in the thermal infrared through coupling to biased GaAs
      semiconductor quantum wells. This tuning mechanism can be scaled from the visible
      to the far infrared by the proper choice of metamaterials and semiconductor
      heterostructures.

PMID- 22418542
TI  - Collective lasing from a linear array of dielectric microspheres with gain.
AB  - We experimentally study the optical emission behavior of a linear array of
      dielectric microspheres with gain. The microspheres are randomly arranged and
      well-separated, and can only couple via radiative modes. We observe resolution
      limited, ultra-narrowband modes in the longitudinal emission, which constitutes
      collective lasing from the entire array, inferred from the observation of a
      lasing threshold. The lasing modes show wavelength selectivity, wherein the
      lasing probability is large only in specific frequency bands while being
      inhibited at other wavelengths, a behavior which is independent of the degree of
      configurational randomness. Analysis of the frequency bands indicates the
      participation of Fabry-Perot resonances of the individual microspheres in the
      collective emission.

PMID- 22418543
TI  - Frequency comb from a microresonator with engineered spectrum.
AB  - We demonstrate that by varying the ratio between the linewidth and dispersion of
      a whispering gallery mode resonator we are able to control the number N of free
      spectral ranges separating the first generated comb sidebands from the pump. We
      observed combs with N = 19 and N = 1. For the comb with N = 1 we have achieved a
      span of over 200 nm using a 0.4 mm MgF2 resonator pumped with 50 mW at 1560 nm.
      This pump power is a factor of 10 lower than previously reported for combs with
      comparable bandwidth.

PMID- 22418544
TI  - Novel coherent self-heterodyne receiver based on phase modulation detection.
AB  - We propose a novel coherent self-heterodyne receiver structure based on phase
      modulation detection that potentially simplifies the front-end of a coherent
      optical receiver. The scheme has been demonstrated via simulations and
      experimentally for a 10 Gb/s DQPSK transmission system.

PMID- 22418545
TI  - Configurable metamaterial absorber with pseudo wideband spectrum.
AB  - Metamaterials attain their behavior due to resonant interactions among their
      subwavelength components and thus show specific designer features only in a very
      narrow frequency band. There is no simple way to dynamically increase the
      operating bandwidth of a narrowband metamaterial, but it may be possible to
      change its central frequency, shifting the spectral response to a new frequency
      range. In this paper, we propose and experimentally demonstrate a metamaterial
      absorber that can shift its central operating frequency by using mechanical
      means. The shift is achieved by varying the gap between the metamaterial and an
      auxiliary dielectric slab parallel to its surface. We also show that it is
      possible to create multiple absorption peaks by adjusting the size and/or shape
      of the dielectric slab, and to shift them by moving the slab relative to the
      metamaterial. Specifically, using numerical simulations we design a microwave
      metamaterial absorber and experimentally demonstrate that its central frequency
      can be set anywhere in a 1.6 GHz frequency range. The proposed configuration is
      simple and easy to make, and may be readily extended to THz frequencies.

PMID- 22418546
TI  - High uniformity in angular correlated-color-temperature distribution of white
      LEDs from 2800K to 6500K.
AB  - In this paper, to our best knowledge, it is the first time to present a precise
      simulation and detailed design of angular correlated color temperature (CCT)
      distribution of white LEDs covering a range of CCT from 2800K to 6500K. An
      optimized design of packaging structure with a silicone lens covering a phosphor
      dome performed an extreme small angular CCT deviation of 105K in the simulation
      and 182K in a corresponding real sample for a white LED with the CCT near 6500K.

PMID- 22418547
TI  - Demonstration of on-sky calibration of astronomical spectra using a 25 GHz near
      IR laser frequency comb.
AB  - We describe and characterize a 25 GHz laser frequency comb based on a cavity
      filtered erbium fiber mode-locked laser. The comb provides a uniform array of
      optical frequencies spanning 1450 nm to 1700 nm, and is stabilized by use of a
      global positioning system referenced atomic clock. This comb was deployed at the
      9.2 m Hobby-Eberly telescope at the McDonald Observatory where it was used as a
      radial velocity calibration source for the fiber-fed Pathfinder near-infrared
      spectrograph. Stellar targets were observed in three echelle orders over four
      nights, and radial velocity precision of ~10 m/s (~6 MHz) was achieved from the
      comb-calibrated spectra.

PMID- 22418548
TI  - Frequency up-conversion of quantum images.
AB  - We develop the theory of frequency up-conversion of an arbitrary spatially
      broadband quantum state (quantum image), deriving the analytical solutions for
      the cases of plane-wave pump and short crystal with arbitrary pump. By using an
      example of the quantum image imposed by the orbital angular momentum of the pump
      beam in spontaneous parametric down-conversion, we show that 99%-fidelity up
      conversion of quantum images from an infrared wavelength to the visible
      wavelength can be obtained in periodically-poled lithium-niobate crystals at
      reasonable pump intensities well below the crystal damage threshold.

PMID- 22418549
TI  - Monolithic integration of binary-phase Fresnel zone plate objectives on 2-axis
      scanning micromirrors for compact microscopes.
AB  - We demonstrated a unique monolithic integration of Fresnel elliptical zone plate
      (EZP) objective on a 2-axis staggered vertical comb-drive micromirror with 500
      MUm by 800 MUm surface area via direct patterning of reflective binary phase
      modulation elements on a silicon chip. The need for focusing optics is thus
      obviated, simplifying the micro-endoscope assembly and improving its form factor.
      The design of binary phase EZP was guided by simulations based on FFT based
      Rayleigh-Sommerfeld diffraction model. For dual-axis scanning angles up to 9o by
      9o at the image plane, the simulated diffracted Airy disks on a spatial map have
      been demonstrated to vary from 10.5 MUm to 28.6 MUm. Micromirrors scanning +/-9o
      (optical) about both axes are patterned with elliptical zones designed for 7 mm
      focal length and 20p off-axis 635-nm illumination using 635 nm laser. Videos of
      samples acquired with ~15 MUm lateral resolution over 1mm * 0.35 mm field of view
      (FOV) at 5.0 frames/second using the device in both transmission and reflectance
      modes bench-top single-fiber laser scanning confocal microscope confirmed the
      applicability of the device to micro-endoscopy.

PMID- 22418550
TI  - Rotation-free holographic imaging with extended arc reference.
AB  - We proposed and experimentally demonstrated a rotation-free approach of
      holographic imaging by using an extended arc reference. From the diffraction
      intensity, the objects were retrieved using a two-step algorithm without a prior
      knowledge of the information of the sample and reference. This scheme alleviates
      the convergence problem of coherent diffractive imaging and also promises to
      achieve a high resolution.

PMID- 22418551
TI  - Delivery of high energy Er:YAG pulsed laser light at 2.94 um through a silica
      hollow core photonic crystal fibre.
AB  - In this paper the delivery of high power Er:YAG laser pulses through a silica
      hollow core photonic crystal fibre is demonstrated. The Er:YAG wavelength of 2.94
      um is well beyond the normal transmittance of bulk silica but the unique hollow
      core guidance allows silica to guide in this regime. We have demonstrated for the
      first time the ability to deliver high energy pulses through an all-silica fibre
      at 2.94 um. These silica fibres are mechanically and chemically robust,
      biocompatible and have low sensitivity to bending. A maximum pulse energy of 14
      mJ at 2.94 um was delivered through the fibre. This, to our knowledge, is the
      first time a silica hollow core photonic crystal fibre has been shown to transmit
      2.94 MUm laser light at a fluence exceeding the thresholds required for
      modification (e.g. cutting and drilling) of hard biological tissue. Consequently,
      laser delivery systems based on these fibres have the potential for the
      realization of novel, minimally-invasive surgical procedures.

PMID- 22418552
TI  - Multiple-soliton dynamic patterns in a graphene mode-locked fiber laser.
AB  - Multiple-soliton dynamic patterns have been observed experimentally in an erbium
      doped fiber ring laser with graphene as a saturable absorber. Under relatively
      low pumping power we have obtained disordered multiple-solitons, bunched solitons
      and high order harmonic mode locking by adjusting the orientation of the
      polarization controllers. With increased pumping power, we have also observed
      flow of solitons. We have experimentally investigated in detail the conditions
      under which these patterns form.

PMID- 22418553
TI  - Optical microscope angular illumination analysis.
AB  - For high precision applications of optical microscopes, it is critical to achieve
      symmetrical angular illumination intensity at the sample plane, in addition to
      uniform spatial irradiance achieved by Kohler illumination. A correlation between
      the angular illumination asymmetry and the contrast in the image of a line
      grating target was demonstrated as the target is scanned through focus. Using
      this correlation, we present a novel, yet simple method of experimentally
      evaluating the angular illumination asymmetry (ANILAS) at the sample plane of an
      optical microscope across the field of view. This ANILAS map is expected to be a
      useful method for assessing the illumination condition of optical systems.

PMID- 22418554
TI  - A polymer-based functional pattern on one-dimensional photonic crystals for
      photon sorting of fluorescence radiation.
AB  - In this work we introduce the use of a patterned polymer-based surface
      functionalization of a one-dimensional photonic crystal (1DPC) for controlling
      the emission direction of fluorescent proteins (ptA) via coupling to a set of two
      Bloch Surface Waves (BSW). Each BSW dispersion branch relates to a micrometric
      region on the patterned 1DPC, characterized by a well defined chemical
      characteristic. We report on the enhanced and spatially selective excitation of
      fluorescent ptA, and on the spatially-resolved detection of polarized emitted
      radiation coupled to specific BSW modes. As a result, we provide an optical
      multiplexing technique for the angular separation of fluorescence radiated from
      micrometric regions having different surface properties, even in the case the
      emitting labels are spectrally identical. This working principle can be
      advantageously extended to a multi-step nanometric relief structure for self
      referencing biosensing or frequency-multiplexed fluorescence detection.

PMID- 22418556
TI  - Non-exponential decay of dark localized surface plasmons.
AB  - It is shown that the decay of the weakly coupled to radiation (dark) modes of
      subwavelength plasmonic nanostructures is strongly nonexponential. Their lifetime
      is overestimated by conventional exponential relaxation time obtained in the
      standard Markovian approximation. These effects are manifestations of the strong
      dispersion and near-field feedback. The developed theoretical framework
      introduces an ensemble of local relaxation degrees of freedom coupled to
      plasmonic mode in order to describe its decay due to material losses. The
      macroscopic description of the decay process leads to the specific memory
      function of the system, evaluated from the modal and material dispersions of the
      plasmonic nanostructure. Proper knowledge of the relaxation behavior is vital for
      various applications relying on light-matter interactions of emitters with
      nanoscale objects, such as fluorescence manipulation, bio-imaging, sensing,
      spasers, sub-diffraction optics, Raman scattering, and quantum optics.

PMID- 22418555
TI  - Optical waveguides in TiO2 formed by He ion implantation.
AB  - We report on the formation and the optical properties of the planar and ridge
      optical waveguides in rutile TiO2 crystal by He+ ion implantation combined with
      micro-fabrication technologies. Planar optical waveguides in TiO2 are fabricated
      by high-energy (2.8 MeV) He+-ion implantation with a dose of 3 * 1016 ions/cm2
      and triple low energies (450, 500, 550) keV He+-ion implantation with all
      fluences of 2 * 1016 ions/cm2 at room temperature. The guided modes were measured
      by a modal 2010 prism coupler at wavelength of 1539 nm. There are damage profiles
      in ion-implanted waveguides by Rutherford backscattering (RBS)/channeling
      measurements. The refractive-index profile of the 2.8 MeV He+-implanted waveguide
      was analyzed based on RCM (Reflected Calculation Method). Also ridge waveguides
      were fabricated by femtosecond laser ablation on 2.8 MeV ion implanted planar
      waveguide and Ar ion beam etching on the basis of triple keV ion implanted planar
      waveguide, separately. The loss of the ridge waveguide was estimated. The
      measured near-field intensity distributions of the planar and ridge modes are all
      shown.

PMID- 22418557
TI  - Nonlinear dispersion-based incoherent photonic processing for microwave pulse
      generation with full reconfigurability.
AB  - A novel all-optical technique based on the incoherent processing of optical
      signals using high-order dispersive elements is analyzed for microwave arbitrary
      pulse generation. We show an approach which allows a full reconfigurability of a
      pulse in terms of chirp, envelope and central frequency by the proper control of
      the second-order dispersion and the incoherent optical source power distribution,
      achieving large values of time-bandwidth product.

PMID- 22418558
TI  - Gradient field microscopy of unstained specimens.
AB  - We present a phase derivative microscopy technique referred to as gradient field
      microscopy (GFM), which provides the first-order derivatives of the phase
      associated with an optical field passing through a transparent specimen. GFM
      utilizes spatial light modulation at the Fourier plane of a bright field
      microscope to optically obtain the derivatives of the phase and increase the
      contrast of the final image. The controllable spatial modulation pattern allows
      us to obtain both one component of the field gradient (derivative along one
      direction) and the gradient intensity, which offers some advantages over the
      regular differential interference contrast (DIC) microscopy. Most importantly,
      unlike DIC, GFM does not use polarizing optics and, thus, it is applicable to
      birefringent samples. We demonstrate these features of GFM with studies of static
      and dynamic biological cells (HeLa cells and red blood cells). We show that GFM
      is capable of qualitatively providing information about cell membrane
      fluctuations. Specifically, we captured the disappearance of the bending mode of
      fluctuations in osmotically swollen red blood cells.

PMID- 22418559
TI  - Broadband bandgap guidance and mode filtering in radially hybrid photonic crystal
      fiber.
AB  - Hybrid Photonic Crystal Fibers with a first ring of high index inclusions are
      studied and compared to both standard air-hole fibers and all solid photonic
      bandgap fibers. In such new fibers a bandgap-like core mode exists over a wide
      spectral range and exhibits confinement losses ten orders of magnitude smaller
      than those of the corresponding all-solid fiber. This particular fiber supports
      also a core mode guided by modified total internal reflection at long enough
      wavelengths. The origin and properties of these two kinds of modes are discussed
      in details. Such a design can also act as a mode filter (as compared to the
      standard air-hole structure) and could also be used to ease phase matching
      conditions for nonlinear optics.

PMID- 22418560
TI  - Common approach for compensation of axial motion artifacts in swept-source OCT
      and dispersion in Fourier-domain OCT.
AB  - Swept-source optical coherence tomography (SS-OCT) is sensitive to sample motion
      during the wavelength sweep, which leads to image blurring and image artifacts.
      In line-field and full-field SS-OCT parallelization is achieved by using a line
      or area detector, respectively. Thus, approximately 1000 lines or images at
      different wavenumbers are acquired. The sweep duration is identically with the
      acquisition time of a complete B-scan or volume, rendering parallel SS-OCT more
      sensitive to motion artifacts than scanning OCT. The effect of axial motion on
      the measured spectra is similar to the effect of non-balanced group velocity
      dispersion (GVD) in the interferometer arms. It causes the apparent optical path
      lengths in the sample arm to vary with the wavenumber. Here we propose the cross
      correlation of sub-bandwidth reconstructions (CCSBR) as a new algorithm that is
      capable of detecting and correcting the artifacts induced by axial motion in line
      field or full-field SS-OCT as well as GVD mismatch in any Fourier-domain OCT (FD
      OCT) setup. By cross-correlating images which were reconstructed from a limited
      spectral range of the interference signal, a phase error is determined which is
      used to correct the spectral modulation prior to the calculation of the A-scans.
      Performance of the algorithm is demonstrated on in vivo full-field SS-OCT images
      of skin and scanning FD-OCT of skin and retina.

PMID- 22418561
TI  - Controlling electromagnetic scattering of a cavity by transformation media.
AB  - Based on the transformation media theory, we proposed a way to control the
      scattering of a cavity, or trench, located on a metallic plane. Specifically, we
      show how is possible to design transformation medium to fill up a cavity with
      arbitrary cross section, which is capable of enhancing the specularly reflection
      wave. As the inverse problem, we also address the design of transformation medium
      coating, which is laid on the metallic plane, to mimic the scattering of the
      cavity. Based on the effective medium theory, the transformation medium for the
      case of a polygonal cavity can be realized by oblique layered structures, and
      each layered structure is consisting of two kinds of isotropic dielectrics, thus
      leading an ease of practical fabrication.

PMID- 22418562
TI  - THz detection of small molecule vapors in the atmospheric transmission windows.
AB  - Using a low power beam of ultrashort THz pulses that propagate in the ambient
      laboratory environment we have measured the rotational signatures of small
      molecule vapors at frequencies within the atmospheric transmission windows. We
      investigate two types of apparatus. In the first type the THz beam propagates
      along a 6.7 meter round trip path that is external to the spectrometer, and which
      contains a long sample tube (5.4 meter round trip path) that holds the analyte
      vapor. The environment of the tube is controlled to simulate dry or humid
      conditions. In the second apparatus the THz beam propagates over a much longer
      170 meter round trip path with analyte vapor contained in a relatively short 1.2
      meter round trip path sample chamber. We describe the rotational signatures for
      each apparatus in the presence of the strong interference from water vapor
      absorption. For the shorter path long-tube apparatus we find that the peak
      detection sensitivity is sufficient to resolve a 1% absorption feature. For the
      more challenging 170 meter path apparatus we find that the peak detection
      sensitivity is sufficient to resolve a 3-5% absorption feature. The experiments
      presented here represent a first step towards using ultrashort THz pulses for
      coherent broad band detection of small molecule gases and vapors under ambient
      conditions.

PMID- 22418563
TI  - Light extraction efficiency improvement by multiple laser stealth dicing in InGaN
      based blue light-emitting diodes.
AB  - We report a multiple laser stealth dicing (multi-LSD) method to improve the light
      extraction efficiency (LEE) of InGaN-based light-emitting diodes (LEDs) using a
      picosecond (Ps) laser. Compared with conventional LEDs scribed by a nanosecond
      (Ns) laser and single stealth-diced LEDs, the light output power (LOP) of the
      LEDs using multi-LSD method can be improved by 26.5% and 11.2%, respectively. The
      enhanced LOP is due to the increased side emission from the large-area roughened
      sidewalls of the sapphire substrates fabricated in the multi-LSD process.
      Numerical simulation results show that the multi-LSD process has little thermal
      damages to the multiple quantum wells (MQWs) of the LEDs.

PMID- 22418564
TI  - Optical trapping via guided resonance modes in a Slot-Suzuki-phase photonic
      crystal lattice.
AB  - A novel photonic crystal lattice is proposed for trapping a two-dimensional array
      of particles. The lattice is created by introducing a rectangular slot in each
      unit cell of the Suzuki-Phase lattice to enhance the light confinement of guided
      resonance modes. Large quality factors on the order of 105 are predicted in the
      lattice. A significant decrease of the optical power required for optical
      trapping can be achieved compared to our previous design.

PMID- 22418565
TI  - Remote THz generation from two-color filamentation: long distance dependence.
AB  - Remote terahertz (THz) generation from two-color filamentation is investigated as
      a function of the onset position of filaments. THz signals emitted by filaments
      produced at distances up to 55 m from the laser source were measured. However,
      from 9 m to 55 m, the THz signal decayed monotonically for increasing onset
      positions. With a simple calculation, the dominant factors associated to this
      decay were identified as group velocity mismatch of the two-color pulses and
      linear diffraction induced by focusing and propagating the second harmonic pulse.

PMID- 22418566
TI  - Photo-configurable embossed liquid crystal alignment layer with high azimuthal
      anchoring strength.
AB  - Herein we describe a photo-alignment layer of improved azimuthal anchoring energy
      comparable to conventional rubbing method. In order to address the inherent low
      anchoring stability of photo-alignment layer, we applied embossing technique to
      conventional photosensitive polymer film, based on the cinnamoyl photoreactive
      groups, to introduce physical micro-groove effect for additional anchoring
      energy. From this, 2.5 * 10-4 J/m2 of azimuthal anchoring energy was achieved,
      which is considered as synergistic effect from both photoinduced chemical
      interaction and physical microgroove alignment. In this study, we conducted
      systematic study on change in anchoring energy as a function of both aspect ratio
      of embossed pattern and UV exposure dose. We also demonstrated fabrication of
      sophisticated multi-domain structure of LC cells and discussed theoretical
      interpretation through LC simulation.

PMID- 22418567
TI  - Femtosecond third-order nonlinear spectra of lead-germanium oxide glasses
      containing silver nanoparticles.
AB  - This work reports on the spectral dependence of both nonlinear refraction and
      absorption in lead-germanium oxide glasses (PbO-GeO2) containing silver
      nanoparticles. We have found that this material is suitable for all-optical
      switching at telecom wavelengths but at the visible range it behaves either as a
      saturable absorber or as an optical limiter.

PMID- 22418568
TI  - Agreement in risk prediction between the 21-gene recurrence score assay (Oncotype
      DX(r)) and the PAM50 breast cancer intrinsic ClassifierTM in early-stage estrogen
      receptor-positive breast cancer.
AB  - PURPOSE: To compare risk assignment by PAM50 Breast Cancer Intrinsic ClassifierTM
      and Oncotype DX_Recurrence Score (RS) in the same population. METHODS: RNA was
      extracted from 151 estrogen receptor (ER)+ stage I-II breast cancers and gene
      expression profiled using PAM50 "intrinsic" subtyping test. RESULTS: One hundred
      eight cases had complete molecular information; 103 (95%) were classified as
      luminal A (n = 76) or luminal B (n = 27). Ninety-two percent (n = 98) had a low
      (n = 59) or intermediate (n = 39) RS. Among luminal A cancers, 70% had low (n =
      53) and the remainder (n = 23) had an intermediate RS. Among luminal B cancers,
      nine were high (33%) and 13 were intermediate (48%) by the RS. Almost all cancers
      with a high RS were classified as luminal B (90%, n = 9). One high RS cancer was
      identified as basal-like and had low ER/ESR1 and low human epidermal growth
      factor receptor 2 (HER2) expression by quantitative polymerase chain reaction in
      both assays. The majority of low RS cases were luminal A (83%, n = 53).
      Importantly, half of the intermediate RS cancers were re-categorized as low risk
      luminal A subtype by PAM50. CONCLUSION: There is good agreement between the two
      assays for high (i.e., luminal B or RS > 31) and low (i.e., luminal B or RS < 18)
      prognostic risk assignment but PAM50 assigns more patients to the low risk
      category. About half of the intermediate RS group was reclassified as luminal A
      by PAM50.

PMID- 22418569
TI  - Capecitabine monotherapy: review of studies in first-line HER-2-negative
      metastatic breast cancer.
AB  - The goals of treatment for metastatic breast cancer (MBC) are to prolong overall
      survival (OS) while maximizing quality of life, palliating symptoms, and delaying
      tumor progression. For many years, anthracyclines and taxanes have been the
      mainstay of treatment for MBC, but these agents are now commonly administered
      earlier in the course of the disease. A recent meta-analysis revealed adverse
      effects on OS and overall response rates in patients with MBC receiving first
      line anthracycline-based chemotherapy following relapse on adjuvant chemotherapy.
      Noncrossresistant cytotoxic agents and combinations that combine high clinical
      activity and acceptable tolerability while being convenient for patients are
      therefore needed for the first-line treatment of MBC patients. Capecitabine has
      substantial antitumor activity in the first-line treatment of patients with MBC
      in prospective, randomized, phase II/III clinical trials as monotherapy and in
      combination with biologic and novel agents. First-line capecitabine monotherapy
      has a favorable safety profile, lacking myelosuppression and alopecia, and does
      not compromise the administration of further lines of chemotherapy. Capecitabine
      is suitable for long-term administration without the cumulative toxicity that can
      limit the prolonged use of other chemotherapy agents. Here, we review the
      available data on capecitabine as a single agent for first-line treatment of
      patients with human epidermal growth factor receptor 2-negative MBC.

PMID- 22418570
TI  - National study of barriers to timely primary care and emergency department
      utilization among Medicaid beneficiaries.
AB  - STUDY OBJECTIVE: We compare the association between barriers to timely primary
      care and emergency department (ED) utilization among adults with Medicaid versus
      private insurance. METHODS: We analyzed 230,258 adult participants of the 1999 to
      2009 National Health Interview Survey. We evaluated the association between 5
      specific barriers to timely primary care (unable to get through on telephone,
      unable to obtain appointment soon enough, long wait in the physician's office,
      limited clinic hours, lack of transportation) and ED utilization (>=1 ED visit
      during the past year) for Medicaid and private insurance beneficiaries.
      Multivariable logistic regression models adjusted for demographics, socioeconomic
      status, health conditions, outpatient care utilization, and survey year. RESULTS:
      Overall, 16.3% of Medicaid and 8.9% of private insurance beneficiaries had
      greater than or equal to 1 barrier to timely primary care. Compared with
      individuals with private insurance, Medicaid beneficiaries had higher ED
      utilization overall (39.6% versus 17.7%), particularly among those with barriers
      (51.3% versus 24.6% for 1 barrier and 61.2% versus 28.9% for >=2 barriers). After
      adjusting for covariates, Medicaid beneficiaries were more likely to have
      barriers (adjusted odds ratio [OR] 1.41; 95% confidence interval [CI] 1.30 to
      1.52) and higher ED utilization (adjusted OR 1.48; 95% CI 1.41 to 1.56). ED
      utilization was even higher among Medicaid beneficiaries with 1 barrier (adjusted
      OR 1.66; 95% CI 1.44 to 1.92) or greater than or equal to 2 barriers (adjusted OR
      2.01; 95% CI 1.72 to 2.35) compared with that for individuals with private
      insurance and barriers. CONCLUSION: Compared with individuals with private
      insurance, Medicaid beneficiaries were affected by more barriers to timely
      primary care and had higher associated ED utilization. Expansion of Medicaid
      eligibility alone may not be sufficient to improve health care access.

PMID- 22418571
TI  - Lipid-based carriers of microRNAs and intercellular communication.
AB  - PURPOSE OF REVIEW: Extracellular microRNAs (miRNAs) are uniquely stable in
      plasma, and the levels of specific circulating miRNAs can differ with disease.
      Extracellular miRNAs are associated with lipid-based carriers and lipid-free
      proteins. miRNAs can be transferred from cell-to-cell by lipid-based carriers and
      affect gene expression. This review summarizes recent studies that demonstrate
      the transfer of miRNA between cells and their potential role in intercellular
      communication. RECENT FINDINGS: Microvesicles, exosomes, apoptotic bodies,
      lipoproteins, and large microparticles contain miRNAs. Recent studies have
      demonstrated that miRNAs are transferred between dendritic cells, hepatocellular
      carcinoma cells, and adipocytes in lipid-based carriers. miRNAs are also
      transferred from T cells to antigen-presenting cells, from stem cells to
      endothelial cells and fibroblasts, from macrophages to breast cancer cells, and
      from epithelial cells to hepatocytes in lipid-based carriers. The cellular export
      of miRNAs in lipid-based carriers is regulated by the ceramide pathway, and the
      delivery of lipid-associated miRNAs to recipient cells is achieved by various
      routes, including endocytotic uptake, membrane-fusion, and scavenger receptors.
      SUMMARY: Cellular miRNAs are exported in and to lipid-based carriers (vesicles
      and lipoprotein particles) and transferred to recipient cells with gene
      expression changes as intercellular communication.

PMID- 22418573
TI  - Current world literature.

PMID- 22418572
TI  - Finding genes and variants for lipid levels after genome-wide association
      analysis.
AB  - PURPOSE OF REVIEW: We review the main findings from genome-wide association
      studies (GWAS) for levels of HDL-cholesterol, LDL-cholesterol and triglycerides,
      including approaches to identify the functional variant(s) or gene(s). We discuss
      study design and challenges related to whole genome or exome sequencing to
      identify novel genes and variants. RECENT FINDINGS: GWAS have detected
      approximately 100 loci associated with one or more lipid trait. Fine mapping of
      several loci for LDL-cholesterol demonstrated that the trait variance explained
      may double when the functional variants responsible for the association signals
      are identified. Experimental follow-up of three loci identified by GWAS has
      identified functional genes GALNT2, TRIB1, and SORT1, and a functional variant at
      SORT1. SUMMARY: The goal of genetic studies for lipid levels is to improve
      treatment and ultimately reduce the prevalence of heart disease. Many signals
      identified by GWAS have modest effect sizes, useful for identifying novel
      biologically relevant genes, but less useful for personalized medicine. Whole
      genome or exome sequencing studies may fill this gap by identifying rare variants
      of larger effect associated with lipid levels and heart disease.

PMID- 22418574
TI  - Genetics and molecular biology:  miRNAs take the HDL ride.

PMID- 22418575
TI  - The role of HDL and its modulators in the development of diabetes.

PMID- 22418576
TI  - Atherosclerosis:  cell biology and lipoproteins - paraoxonases protect against
      atherosclerosis and diabetes development.

PMID- 22418577
TI  - Targeting HDL-cholesterol to reduce residual cardiovascular risk.

PMID- 22418579
TI  - Human hematopoietic prostaglandin D synthase inhibitor complex structures.
AB  - In mast and Th2 cells, hematopoietic prostaglandin (PG) D synthase (H-PGDS)
      catalyses the isomerization of PGH(2) in the presence of glutathione (GSH) to
      produce the allergic and inflammatory mediator PGD(2). We determined the X-ray
      structures of human H-PGDS inhibitor complexes with 1-amino-4-{4-[4-chloro-6-(2
      sulpho-phenylamino)-[1,3,5]triazin-2-ylmethyl]-3-sulpho-phenylamino}-9,10-dioxo
      9,10-dihydro-anthracene-2-sulphonic acid (Cibacron Blue) and 1-amino-4-(4
      aminosulphonyl) phenyl-anthraquinone-2-sulphonic acid (APAS) at 2.0 A resolution.
      When complexed with H-PGDS, Cibacron Blue had an IC(50) value of 40 nM and APAS
      2.1 MUM. The Cibacron Blue molecule was stabilized by four hydrogen bonds and pi
      pi stacking between the anthraquinone ring and Trp104, the ceiling of the active
      site H-PGDS pocket. Among the four hydrogen bonds, the Cibacron Blue terminal
      sulphonic group directly interacted with conserved residues Lys112 and Lys198,
      which recognize the PGH(2) substrate alpha-chain. In contrast, the APAS
      anthraquinone ring was inverted to interact with Trp104, while its
      benzenesulphonic group penetrated the GSH-bound region at the bottom of the
      active site. Due to the lack of extended aromatic rings, APAS could not directly
      hydrogen bond with the two conserved lysine residues, thus decreasing the total
      number of hydrogen bond from four to one. These factors may contribute to the 50
      fold difference in the IC(50) values obtained for the two inhibitors.

PMID- 22418580
TI  - Moyamoya disorder in the United States.
AB  - BACKGROUND: In Asian populations, moyamoya disease has a well-defined phenotype
      including a bimodal age of presentation with children typically presenting with
      ischemic phenomena and adults presenting with hemorrhage. Studies have provided
      evidence that moyamoya disease in the United States may exhibit a different
      phenotype. OBJECTIVE: To assess overall rates of admission, demographics,
      procedures, and outcomes of patients admitted or diagnosed with moyamoya disorder
      in US hospitals. METHODS: A comprehensive assessment of the Nationwide Inpatient
      Sample of the Healthcare Cost and Utilization Project (2002-2008) was performed.
      Patient demographics, comorbidities, procedures, and outcomes were analyzed.
      RESULTS: There were 2280 admissions for moyamoya disorder with a predicted
      national estimate of 11 163 admissions (0.57/100 000 persons/y). Over time, there
      was a significant increase in diagnosis and associated ischemic strokes. Females
      (72%) were affected more than males (28%). Demographics included white (49%),
      black (24%), Hispanic (11%), Asian (11%), and other (3.3%). Mean age at
      presentation was 31.6 +/- 18.0. Children were significantly more likely to be
      diagnosed with ischemic phenomena (16.4%) than hemorrhage (3.3%), as were adults
      (18.8% vs 11.0%). Status at discharge was largely routine (74.8%) vs short-term
      hospital (3%), home health care (7%), transfer to another hospital (12%), or in
      hospital death in 2.3%. CONCLUSION: Patients admitted to US hospitals diagnosed
      with moyamoya disorder were more commonly female and white, and both adults and
      children were more likely to be diagnosed with ischemic vs hemorrhagic stroke.
      Over time, there was an increase in diagnosis, associated ischemic stroke, and
      treatment with extracranial-intracranial bypass.

PMID- 22418581
TI  - Comparison of infection rate with the use of antibiotic-impregnated vs standard
      extraventricular drainage devices: a prospective, randomized controlled trial.
AB  - BACKGROUND: External ventricular drainage (EVD) catheters provide reliable and
      accurate means of monitoring intracranial pressure and alleviating elevated
      pressures via drainage of cerebrospinal fluid (CSF). CSF infections occur in
      approximately 9% of patients. Antibiotic-impregnated (AI) EVD catheters were
      developed with the goal of reducing the occurrence of EVD catheter-related CSF
      infections and their associated complications. OBJECTIVE: To present an
      international, prospective, randomized, open-label trial to evaluate infection
      incidence of AI vs standard EVD catheters. METHODS: Infection was defined as (1)
      proven infection, positive CSF culture and positive Gram stain or (2) suspected
      infection: (A) positive CSF culture with no organisms identified on initial Gram
      stain; (B) negative CSF culture with a gram-positive or -negative stain; (C) CSF
      leukocytosis with a white blood cell/red blood cell count >0.02. RESULTS: Four
      hundred thirty-four patients underwent implantation of an EVD catheter. One
      hundred seventy-six patients in the AI-EVD cohort and 181 in the standard EVD
      catheter cohort were eligible for evaluation of infection. The 2 groups were
      similar in all clinical characteristics. Proven infection was documented in 9
      (2.5%) patients (AI: 4 [2.3%] vs standard: 5 [2.8%], P = 1.0). Suspected
      infection was documented in 31 (17.6%) patients receiving AI and 37 (20.4%)
      patients receiving standard EVD catheters, P = .504. Duration of time to
      suspected infection was prolonged in the AI cohort (8.8 +/- 6.1 days) compared
      with the standard EVD cohort (4.6 +/- 4.2 days), P = .002. CONCLUSION: AI-EVD
      catheters were associated with an extremely low rate of catheter-related
      infections. AI catheters were not associated with risk reduction in EVD infection
      compared to standard catheters. Use of AI-EVD catheters is a safe option for a
      wide variety of patients requiring CSF drainage and monitoring, but the efficacy
      of AI-EVD catheters was not supported in this trial.

PMID- 22418582
TI  - Occipital nerve stimulation for refractory headache in the Chiari malformation
      population.
AB  - BACKGROUND: Chronic occipital and suboccipital headache is a common symptom in
      patients with Chiari I malformation. These headaches may persist despite
      appropriate surgical treatment of the underlying pathology via suboccipital
      decompression, duraplasty, and cerebrospinal fluid diversion. Occipital nerve
      stimulation has been shown to be effective in the treatment of a variety of
      occipital headache/pain syndromes. OBJECTIVE: To review retrospectively our
      experience with occipital nerve stimulation in patients with a primary diagnosis
      of Chiari malformation and a history of chronic occipital pain intractable to
      medical and surgical therapies. METHODS: We present a retrospective analysis of
      our series of 22 patients with Chiari malformation and persistent occipital
      headaches who underwent occipital neurostimulator trials and, after successful
      trials, permanent stimulator placement. A trial was considered successful with
      >50% pain relief as assessed with a standard Visual Analog Scale score. Patients
      with a successful trial underwent permanent placement approximately 1 to 2 weeks
      later. Patients were assessed postoperatively for pain relief via the Visual
      Analog Scale. RESULTS: Sixty-eight percent of patients (15 of 22) had a
      successful stimulator trial and proceeded to permanent implantation. Of those
      implanted, 87% (13 of 15) reported continued pain relief at a mean follow-up of
      18.9 months (range, 6-51 months). Device-related complications requiring
      additional surgeries occurred in 40% of patients. CONCLUSION: Occipital
      stimulation may provide significant long-term pain relief in selected Chiari I
      malformation patients with persistent occipital pain. Larger and longer-term
      studies are needed to further define appropriate patient selection criteria and
      to refine the surgical technique to minimize device-related complications.

PMID- 22418583
TI  - Role of cancer stem cells in spine tumors:  review of current literature.
AB  - The management of spinal column tumors continues to be a challenge for
      clinicians. The mechanisms of tumor recurrence after surgical intervention as
      well as resistance to radiation and chemotherapy continue to be elucidated.
      Furthermore, the pathophysiology of metastatic spread remains an area of active
      investigation. There is a growing body of evidence pointing to the existence of a
      subset of tumor cells with high tumorigenic potential in many spine cancers that
      exhibit characteristics similar to those of stem cells. The ability to self-renew
      and differentiate into multiple lineages is the hallmark of stem cells, and tumor
      cells that exhibit these characteristics have been described as cancer stem cells
      (CSCs). The mechanisms that allow nonmalignant stem cells to promote normal
      developmental programming by way of enhanced proliferation, promotion of
      angiogenesis, and increased motility may be used by CSCs to fuel carcinogenesis.
      The purpose of this review is to discuss what is known about the role of CSCs in
      tumors of the osseous spine. First, this article reviews the fundamental concepts
      critical to understanding the role of CSCs with respect to chemoresistance,
      radioresistance, and metastatic disease. This discussion is followed by a review
      of what is known about the role of CSCs in the most common primary tumors of the
      osseous spine.

PMID- 22418584
TI  - Community-dwelling people with chronic stroke need disproportionate attention
      while walking and negotiating obstacles.
AB  - The objective of the present study was to examine the attentional demands of gait
      adaptations required to walk over irregular terrain in community-dwelling people
      with chronic stroke. Eight community ambulators (>6 months post-stroke, aged 57
      +/- 15 years) and eight age-matched healthy controls participated in the study.
      As the primary motor task, participants walked on a treadmill while they quickly
      reacted to a sudden obstacle in front of the affected (in the stroke group) or
      left (in healthy controls) leg. The secondary, cognitive task was an auditory
      Stroop task. Outcomes were avoidance success rate and muscle reaction times of
      the biceps and rectus femoris (motor task), and a composite score of accuracy and
      verbal reaction time (cognitive task). Success rates did not differ between
      single- and dual-task conditions in either group, while muscle reaction times
      deteriorated equally during the dual task in both groups. However, compared with
      the Stroop scores just before and after obstacle crossing, the scores while
      crossing the obstacle deteriorated more in the stroke group than in the controls
      (p=0.012). The higher dual-task costs on the Stroop task reflect greater
      attentional demands during walking and crossing obstacles. The absence of dual
      task effects on obstacle avoidance performance suggests that the people with
      stroke used a "posture-first strategy". The results imply that common daily life
      tasks such as obstacle crossing while walking require disproportionate attention
      even in well-recovered people with stroke.

PMID- 22418585
TI  - Medication improves balance and complex gait performance in Parkinson disease.
AB  - Gait and balance impairments in people with Parkinson disease (PD) may lead to
      falls and serious injuries. Therefore, it is critical to improve our
      understanding of the nature of these impairments, including how they respond to
      prescribed anti-Parkinson medication. This is particularly important for complex
      balance and gait tasks that may be associated with falls. We evaluated motor
      function, functional balance, and gait performance during various gait tasks in
      22 people with PD OFF and ON medication (PD OFF, PD ON) and 20 healthy older
      adults. Although MDS-UPDRS-III score, Berg Balance Scale, Mini-Balance
      Evaluations Systems test, and Timed-Up-and-Go improved in PD with medication,
      impairments persisted in all measures on medication, compared to controls. Dual
      task Timed-Up-and-Go did not improve with medication, and PD ON required more
      time than controls. Gait velocity and stride length improved similarly with
      medication in PD across forward, fast, backward, dual task forward, and dual task
      backward gait tasks. Cadence did not change with medication, nor did it differ
      between PD ON and controls. Velocity and stride length were reduced in PD ON
      compared to controls. Velocity reductions in PD ON during fast gait were cadence
      mediated, while velocity reductions in backward gait were stride length-mediated.
      Our results suggest functional balance improves with medication in PD and gait
      performance improves with medication, regardless of task complexity. Remaining
      impairments on medication highlight the need to examine additional therapeutic
      options for individuals with PD to reduce the risk of falls.

PMID- 22418586
TI  - Exposure to ambient air fine particulate matter prevents VEGF-induced
      mobilization of endothelial progenitor cells from the bone marrow.
AB  - BACKGROUND: Exposure to ambient fine particulate matter air pollution (PM(2.5); <
      2.5 um in aerodynamic diameter) induces endothelial dysfunction and increases the
      risk for cardiovascular disease. Endothelial progenitor cells (EPCs) contribute
      to postnatal endothelial repair and regeneration. In humans and mice, EPC levels
      are decreased upon exposure to elevated levels of PM(2.5). OBJECTIVE: We examined
      the mechanism by which PM(2.5) exposure suppresses circulating levels of EPCs.
      METHODS: Mice were exposed to HEPA-filtered air or concentrated ambient fine
      particulate matter (CAP, 30-100 ug/m3) from downtown Louisville (Kentucky) air,
      and progenitor cells from peripheral blood or bone marrow were analyzed by flow
      cytometry or by culture ex vivo. RESULTS: Exposure of the mice to CAP (6 hr/day)
      for 4-30 days progressively decreased circulating levels of EPCs positive for
      both Flk-1 and Sca-1 (Flk-1(+)/Sca-1(+)) without affecting stem cells positive
      for Sca-1 alone (Sca-1(+)). After 9 days of exposure, a 7-day exposure-free
      period led to complete recovery of the circulating levels of Flk-1(+)/Sca-1(+)
      cells. CAP exposure decreased circulating levels of EPCs independent of apoptosis
      while simultaneously increasing Flk-1(+)/Sca-1(+) cells in the bone marrow. We
      observed no change in tissue deposition of these cells. CAP exposure suppressed
      vascular endothelial growth factor (VEGF)-induced Akt and endothelial nitric
      oxide synthase (eNOS) phosphorylation in the aorta, and it prevented VEGF/AMD3100
      induced mobilization of Flk-1(+)/Sca-1(+) cells into the peripheral blood.
      Treatment with stem cell factor/AMD3100 led to a greater increase in circulating
      Flk-1(+)/Sca-1(+) cells in CAP-exposed mice than in mice breathing filtered air.
      CONCLUSION: Exposure to PM(2.5) increases EPC levels in the bone marrow by
      preventing their mobilization to the peripheral blood via inhibition of signaling
      events triggered by VEGF-receptor stimulation that are upstream of c-kit
      activation. Suppression of EPC mobilization by PM(2.5) could induce deficits in
      vascular repair or regeneration.

PMID- 22418587
TI  - Differential expression of membrane proteins helps Antarctic Pseudomonas syringae
      to acclimatize upon temperature variations.
AB  - Antarctic bacteria are adapted to the extremely low temperature. The
      transcriptional and translational machineries of these bacteria are adapted to
      the sub-zero degrees of temperature. Studies directed towards identifying the
      changes in the protein profiles during changes in the growth temperatures of an
      Antarctic bacterium Pseudomonas syringae Lz4W may help in understanding the
      molecular basis of cold adaptation. In this study, subcellular fractionation
      methods of proteins were used for the enrichment and identification of proteins
      including low abundance proteins. The membrane proteins of the bacterium P.
      syringae Lz4W were prepared employing sucrose density gradient method. The
      proteins were separated through 2D gel-electrophoresis with the pH ranges 3-10, 4
      7 and 5-8 using the detergent, amidosulfobetaine (ASB-14). The proteins separated
      on the 1D SDS PAGE and 2D gels were identified with the help of LC-ESI MS/MS and
      MALDI TOF TOF using bioinformatic programs MASCOT and SEQUEST. Since the genome
      sequence of P. syringae Lz4W is not available, the proteins are identified by
      using the genome database of the Pseudomonas sp. available at NCBI. The present
      studies focus on identifying temperature dependent expression of proteins by
      employing LC-MS/MS method and the functional significance of these proteins is
      discussed.

PMID- 22418588
TI  - Cerebral metastases in extrapulmonary cell carcinoma. Implications for the use of
      prophylactic cranial irradiation.
AB  - BACKGROUND AND PURPOSE: Extrapulmonary small cell carcinoma (EPSCC) is a rare
      disease. Standard treatment is performed in analogy to small cell lung cancer;
      however, due to the differences in rates of cerebral metastases (CM),
      prophylactic cranial irradiation (PCI) is not routinely used. Therefore, we
      evaluated the characteristics of all patients developing brain metastases in a
      population of EPSCC patients and calculated a number needed to treat (NNT) for
      the prevention of cerebral metastases by PCI. PATIENTS, METHODS, AND RESULTS: Of
      51 patients treated at our institution from 1999-2011 for EPSCC, 11 presented
      with CM, 5 at initial diagnosis, 6 in the course of their disease. Median overall
      survival after primary diagnosis of EPSCC was 12 months. Overall survival after
      diagnosis of CM was significantly in favor of primarily cerebrally metastasized
      patients with 9 compared to 2 months for secondary CM (p = 0.04), median survival
      for all patients being 4 months. The NNT calculation was based on the 6 patients
      with secondary brain metastases in our series and a relative risk reduction of
      60% observed in the studies of PCI for small cell lung cancer (SCLC), resulting
      in an NNT of 13. CONCLUSION: Although the frequency of brain metastases in EPSCC
      was lower than in SCLC, the NNT of 13 for the prevention of CM, as well as the
      poor median survival after diagnosis of secondary brain metastases of 2 months
      might be a reason to discuss and evaluate PCI for EPSCC patients responding to
      initial therapy.

PMID- 22418589
TI  - Do patients with a limited number of brain metastases need whole-brain
      radiotherapy in addition to radiosurgery?
AB  - BACKGROUND: About 40% of patients with brain metastases have a very limited
      number of lesions and may be candidates for radiosurgery. Radiosurgery alone is
      superior to whole-brain radiotherapy (WBRT) alone for control of treated and new
      brain metastases. In patients with a good performance status, radiosurgery also
      resulted in better survival. However, the question is whether the results of
      radiosurgery alone can be further improved with additional WBRT. METHODS:
      Information for this review was compiled by searching the PubMed and MEDLINE
      databases. Very important published meeting abstracts were also considered.
      RESULTS: Based on both retrospective and prospective studies, the addition of
      WBRT to radiosurgery improved control of treated and new brain metastases but not
      survival. However, because a recurrence within the brain has a negative impact on
      neurocognitive function, it is important to achieve long-term control of brain
      metastases. CONCLUSION: The addition of WBRT provides significant benefits.
      Further randomized studies including adequate assessment of neurocognitive
      function and a follow-up period of at least 2 years are needed to help customize
      the treatment for individual patients.

PMID- 22418590
TI  - Ocular and cervical vestibular evoked myogenic potentials in multiple sclerosis
      patients.
AB  - OBJECTIVE: Vestibular evoked myogenic potentials (VEMPs) are thought to provide
      useful information about brainstem functions, as the neural pathways of both
      ocular and cervical VEMPs pass through the brainstem. The aim of this study was
      to investigate the clinical value of ocular and cervical VEMP tests in the
      evaluation of brainstem involvement in multiple sclerosis (MS) patients and to
      assess their relation with clinical and cranial MRI findings. METHODS: Ocular and
      cervical VEMPs were recorded in 62 MS patients and 35 age and sex matched healthy
      volunteers. The latencies, amplitude asymmetry ratios of both VEMP responses and
      abnormality ratios (prolonged latencies and absent responses) were compared
      between the MS patients and the control group and among the groups of MS
      patients. RESULTS: oVEMP mean n1 and p1 latencies and cVEMP mean p13 latency were
      significantly prolonged in MS patients. Although the abnormality ratios of both
      VEMPs were higher in patients with brainstem clinical or MRI lesions, the
      correlation was not statistically significant. Both ocular and cervical VEMP
      latencies were significantly correlated with expanded disability status scale.
      CONCLUSIONS: Although there is no significant correlation with clinical or MRI
      findings, MS patients show high frequency of abnormality in VEMP tests,
      especially in oVEMP tests. SIGNIFICANCE: VEMP tests may be useful as an adjunct
      test in the evaluation of brainstem dysfunction in MS patients.

PMID- 22418591
TI  - Diagnostic value of cauda equina motor conduction time in lumbar spinal stenosis.
AB  - OBJECTIVE: Lumbar spinal stenosis (LSS) is a chronic degenerative disease with
      pain in the back, buttocks and legs aggrevated by walking and relieved after rest
      without associated vascular disease of lower extremities observed in patients
      between 50 and 60 years. Several studies, using different methods indicated an
      association between slowing or blocking of root-nerve conduction and LSS. None of
      the previous research had applied the more conceivable methods such as recording
      the cauda equina potentials from the lumbar level or stimulating the spinal roots
      within the canal using either leg nerves or muscles. In this study, electrical
      lumbar laminar stimulation was used to demonstrate prolongation of cauda equina
      motor conduction time in lumbar spinal stenosis. METHODS: Twenty-one LSS patients
      and age matched 15 normal control subjects were included in the study. Lumbar
      laminar electrical stimulation from L1 and L5 vertebra levels were applied by
      needle electrodes. Compound muscle action potential (CMAP) from gastrocnemius
      muscles were recorded bilaterally. Latency difference of CMAPs obtained from L1
      and L5 spine levels were accepted as the cauda equina motor conduction time
      (CEMCT). RESULTS: CEMCT was significantly longer in patient group when compared
      to normal controls. Mean latency difference was 3.59 +/- 1.07 msec on the right
      side, 3.49 +/- 1.07 msec on the left side in LSS group, it was 1.45 +/- 0.65 msec
      on the right side, 1.35 +/- 0.68 msec on the left side on normal control group
      (p<0.0001). CONCLUSIONS: The prolongation of CEMCT was statistically and
      individually significant in patient group. This may indicate that lower
      lumbosacral motor roots were locally and chronically compressed due to lumbar
      spinal stenosis. Lumbar spinal stenosis may have induced local demyelination at
      the cauda equina level. SIGNIFICANCE: Since the prolongation of CEMCT was found
      only in patients with LSS, the method of laminar stimulation can be chosen for
      patients with uncertain diagnosis of LSS.

PMID- 22418593
TI  - Detection of temporal lobe seizures and identification of lateralisation from
      audified EEG.
AB  - OBJECTIVE: To investigate the accuracy of human listeners in identifying
      epileptic seizures and seizure lateralisation from audified EEG signals. METHODS:
      EEG data from 17 temporal lobe epilepsy patients (9 male, 8 female; aged 23-55)
      was converted to audio format by 60* time compression. Using a subset of 19% of
      the data, five auditory participants (2 female, 3 male; aged 23-58) were trained
      to identify seizures and their lateralisation by listening to audified EEG
      signals from difference electrodes P3-T5 and P4-T6. Following training, seizure
      detection performance of the auditory participants was tested using the remaining
      data. RESULTS: Allowing a 5s auditory time margin for successful detection, the
      mean sensitivity of the five auditory participants was 89.6% (SD 8.3%) with a
      false detection rate of only 0.0068/h (SD 0.0077/h). The mean accuracy of seizure
      lateralisation identification was 77.6% (SD 7.1%). CONCLUSIONS: With a limited
      amount of training, humans can detect seizures and seizure lateralisation from
      audified EEG signals of electrodes P3-T5 and P4-T6 with accuracy comparable to
      visual assessment of full EEG traces (21 electrodes) by an expert
      encephalographer. SIGNIFICANCE: A more efficient and accurate clinical tool for
      assessing EEG data based on audification may be developed, which will improve
      diagnosis and treatment of epilepsy.

PMID- 22418592
TI  - Limb segment load inhibits post activation depression of soleus H-reflex in
      humans.
AB  - OBJECTIVE: We investigated the effect of various doses of limb segment load on
      soleus H-reflex amplitude and post activation depression in healthy individuals.
      We also explored the influence of limb segment load on spinal circuitry in one
      individual with chronic SCI. METHODS: Twenty-eight healthy adults and one SCI
      subject received compressive loads applied to the top of their knee at varied
      doses of load (10%, 25%, and 50% of the body weight). Soleus H-reflexes were
      measured before (baseline) and during the loading phase. RESULTS: There were no
      significant differences in H-reflex amplitudes during the 50% BW load-on phase as
      compared to either baseline session or the load-off phase. However, the post
      activation depression was decreased over 9% (p<0.05) during the load-on phase
      compared to the load-off phase and scaled according to load (50%>25%>10%). The
      post activation depression ratio also appears less responsive to varying loads
      after chronic SCI. CONCLUSIONS: Limb segment load decreases post-activation
      depression in humans. These findings suggest that the mechanism associated with
      post activation depression is modulated by limb segment load, and may be
      influenced by spinal reorganization after SCI. SIGNIFICANCE: Future studies will
      determine if various levels of spasticity modulate the response of limb segment
      load on post activation depression in those with acute and chronic SCI.

PMID- 22418594
TI  - Structural, static and dynamic magnetic properties of dextran coated gamma
      Fe(2)O(3) nanoparticles studied by (57)Fe NMR, Mossbauer, TEM and magnetization
      measurements.
AB  - The structural and magnetic properties and spin dynamics of dextran coated and
      uncoated gamma-Fe(2)O(3) (maghemite) nanoparticles have been investigated using
      high resolution transmission electron microscopy (HRTEM), (57)Fe nuclear magnetic
      resonance (NMR), Mossbauer spectroscopy and dc magnetization measurements. The
      HRTEM observations indicated a well-crystallized system of ellipsoid-shaped
      nanoparticles, with an average size of 10 nm. The combined Mossbauer and magnetic
      study suggested the existence of significant interparticle interactions not only
      in the uncoated but also in the dextran coated nanoparticle assemblies. The zero
      field NMR spectra of the nanoparticles at low temperatures are very similar to
      those of the bulk material, indicating the same hyperfine field values at
      saturation in accord with the performed Mossbauer measurements. The T(2) NMR spin
      spin relaxation time of the nanoparticles has also been measured as a function of
      temperature and found to be two orders of magnitude shorter than that of the bulk
      material. It is shown that the thermal fluctuations in the longitudinal
      magnetization of the nanoparticles in the low temperature limit may account for
      the shortening and the temperature dependence of the T(2) relaxation time. Thus,
      the low temperature NMR results are in accord with the mechanism of collective
      magnetic excitations, due to the precession of the magnetization around the easy
      direction of the magnetization at an energy minimum, a mechanism originally
      proposed to interpret Mossbauer experiments in magnetic nanoparticles. The effect
      of the surface spins on the NMR relaxation mechanisms is also discussed.

PMID- 22418595
TI  - Suppression of nanosilica particle-induced inflammation by surface modification
      of the particles.
AB  - It has gradually become evident that nanomaterials, which are widely used in
      cosmetics, foods, and medicinal products, could induce substantial inflammation.
      However, the roles played by the physical characteristics of nanomaterials in
      inflammatory responses have not been elucidated. Here, we examined how particle
      size and surface modification influenced the inflammatory effects of nanosilica
      particles, and we investigated the mechanisms by which the particles induced
      inflammation. We compared the inflammatory effects of silica particles with
      diameters of 30-1,000 nm in vitro and in vivo. In macrophages in vitro, 30- and
      70-nm nanosilica particles (nSP30 and nSP70) induced higher production of tumor
      necrosis factor-alpha (TNFalpha) than did larger particles. In addition,
      intraperitoneal injection of nSP30 and nSP70 induced stronger inflammatory
      responses involving cytokine production than did larger particles in mice. nSP70
      induced TNFalpha production in macrophage depended on the production of reactive
      oxygen species and the activation of mitogen-activated protein kinases (MAPKs).
      Furthermore, nSP70-induced inflammatory responses were dramatically suppressed by
      surface modification of the particles with carboxyl groups in vitro and in vivo;
      the mechanism of the suppression involved reduction in MAPK activation. These
      results provide basic information that will be useful for the development of safe
      nanomaterials.

PMID- 22418596
TI  - Biological interactions and toxicity of nanomaterials in the respiratory tract
      and various approaches of aerosol generation for toxicity testing.
AB  - After deposition in the respiratory tract, nanoparticles exhibit acute,
      neutrophil-driven inflammatory and oxidative reactions, fibrotic responses and in
      chronic studies under overload conditions carcinogenic effects, more severely
      than the microscaled materials of the same chemistry. Besides these effects also
      known to be induced by microsized particles, nanoparticles principally can
      translocate from the site of exposure to circulation and become systemically
      available. This may either increase the toxic outcome (e.g. cardio-vascular
      effects and potential responses in remote organs) or facilitate an elimination of
      nanomaterials. For example, in combination with partial dissolution, a strong
      lung response after a short-term inhalative exposure may be followed by a rapid
      recovery effect. Mechanistically, in vitro and in vivo tests demonstrated that
      nanoparticles induce inflammation and oxidative stress after interaction with
      macrophages and lung epithelial cells; consequently, a cytotoxic and genotoxic
      potential may exist. The deposition, retention and clearance behaviour of inhaled
      nanomaterials and the toxic effects observed are decisively dependent on the
      particle agglomeration status of the aerosol. Two principally different
      experimental approaches are used for inhalative exposure to nanoparticles: either
      (1) a basic research-oriented approach using very small aerosol mass
      concentrations or particle formulations that result in at least partially
      nanoscaled aerosols; in this way, the potential hazard and the translocation
      potential for individual nanoparticles can be followed effectively; or (2)
      exposure scenarios mimicking the occupational situation (risk-oriented) with
      mostly agglomerated nanoparticles; consequently, the probable risk deriving from
      incidental/accidental exposure can be assessed more adequately.

PMID- 22418597
TI  - Small difference in carcinogenic potency between GBP nanomaterials and GBP
      micromaterials.
AB  - Materials that can be described as respirable granular biodurable particles
      without known significant specific toxicity (GBP) show a common mode of
      toxicological action that is characterized by inflammation and carcinogenicity in
      chronic inhalation studies in the rat. This study was carried out to compare the
      carcinogenic potency of GBP nanomaterials (primary particle diameter 1-100 nm) to
      GBP micromaterials (primary particle diameter >100 nm) in a pooled approach. For
      this purpose, the positive GBP rat inhalation carcinogenicity studies have been
      evaluated. Inhalation studies on diesel engine emissions have also been included
      due to the fact that the mode of carcinogenic action is assumed to be the same.
      As it is currently not clear which dose metrics may best explain carcinogenic
      potency, different metrics have been considered. Cumulative exposure
      concentrations related to mass, surface area, and primary particle volume have
      been included as well as cumulative lung burden metrics related to mass, surface
      area, and primary particle volume. In total, 36 comparisons have been conducted.
      Including all dose metrics, GBP nanomaterials were 1.33- to 1.69-fold (mean
      values) and 1.88- to 3.54-fold (median values) more potent with respect to
      carcinogenicity than GBP micromaterials, respectively. Nine of these 36
      comparisons showed statistical significance (p < 0.05, U test), all of which
      related to dose metrics based on particle mass. The maximum comparative potency
      factor obtained for one of these 9 dose metric comparisons based on particle mass
      was 4.71. The studies with diesel engine emissions did not have a major impact on
      the potency comparison. The average duration of the carcinogenicity studies with
      GBP nanomaterials was 4 months longer (median values 30 vs. 26 months) than the
      studies with GBP micromaterials, respectively. Tumor rates increase with age and
      lung tumors in the rat induced by GBP materials are known to appear late, that
      is, mainly after study durations longer than 24 months. Taking the different
      study durations into account, the real potency differences were estimated to be
      twofold lower than the relative potency factors identified. In conclusion, the
      chronic rat inhalation studies with GBP materials indicate that the difference in
      carcinogenic potency between GBP nanomaterials and GBP micromaterials is low can
      be described by a factor of 2-2.5 referring to the dose metrics mass
      concentration.

PMID- 22418598
TI  - Cytotoxicity of peptide-coated silver nanoparticles on the human intestinal cell
      line Caco-2.
AB  - Silver nanoparticles are used in a wide range of consumer products such as
      clothing, cosmetics, household goods, articles of daily use and pesticides.
      Moreover, the use of a nanoscaled silver hydrosol has been requested in the
      European Union for even nutritional purposes. However, despite the wide
      applications of silver nanoparticles, there is a lack of information concerning
      their impact on human health. In order to investigate the effects of silver
      nanoparticles on human intestinal cells, we used the Caco-2 cell line and peptide
      coated silver nanoparticles with defined colloidal, structural and interfacial
      properties. The particles display core diameter of 20 and 40 nm and were coated
      with the small peptide L-cysteine L-lysine L-lysine. Cell viability and
      proliferation were measured using Promegas CellTiter-Blue(r) Cell Viability
      assay, DAPI staining and impedance measurements. Apoptosis was determined by
      Annexin-V/7AAD staining and FACS analysis, membrane damage with Promegas LDH
      assay and reactive oxygen species by dichlorofluorescein assay. Exposure of
      proliferating Caco-2 cells to silver nanoparticle induced decreasing adherence
      capacity and cytotoxicity, whereby the formation of reactive oxygen species could
      be the mode of action. The effects were dependent on particle size (20, 40 nm),
      doses (5-100 MUg/mL) and time of incubation (4-48 h). Apoptosis or membrane
      damage was not detected.

PMID- 22418599
TI  - Hematopoietic progenitor cell transplantation toxicities in multiple myeloma
      patients with bisphosphonate-induced osteonecrosis of the jaw: a longitudinal
      cohort study.
AB  - PURPOSE: There is no information regarding the toxicity associated with
      autologous hematopoietic progenitor cell transplantation (AHPCT) in patients with
      multiple myeloma (MM) who have bisphosphonate-induced osteonecrosis of the jaw
      (ONJ). There is also limited information regarding long-term outcome of these
      patients. METHODS: In this retrospective cohort study, we compared the toxicity
      after AHPCT in MM patients with and without ONJ. We also analyzed the response
      rate and overall survival of this population of patients. RESULTS: During the
      study period, 176 patients underwent AHPCT at our institution for MM. Ten
      patients with ONJ prior to AHPCT were matched to 40 control patients without ONJ.
      The incidence and severity of transplantation-associated toxicities were similar
      in both groups, including mucositis, 50 % in patients with ONJ vs. 68 % in
      controls (p = 0.889) and febrile days, median 1 vs. 3 days, respectively (p =
      0.524). Myeloid engraftment and hospital length of stay were also similar between
      patients with ONJ and controls. There were significantly more complete remissions
      in patients with ONJ than in control patients (45 % vs. 15 %, p = 0.0336), but
      survival between the groups was not significantly different (log-rank p =
      0.0818). CONCLUSIONS: We conclude that the incidence and severity of
      transplantation-associated toxicities are similar in MM patients with and without
      ONJ. Long-term survival was also similar between both groups.

PMID- 22418600
TI  - Navigating the advanced cancer experience of underserved Latinas.
AB  - OBJECTIVE: Previous cancer research does not adequately inform us about the
      experiences of managing a more serious, life-threatening cancer condition,
      especially for underserved Latinas. This study was designed to explore the ways
      in which Latinas navigate through and deal with advanced cancers. METHODS: A
      purposive sample of 24 underserved Latina women was selected from a randomized
      controlled trial. Data were analyzed using a phenomenological approach to explore
      navigation of the advanced cancer experience. RESULTS: This study outlines a
      conceptual framework which denotes the interconnectedness of multiple factors
      that influence the cancer experience for Latina women. Experiences with advanced
      cancer were embedded within a social, cultural, and systemic framework described
      as 1) intrapersonal experiences; 2) interpersonal experiences; 3) provider
      interactions; and 4) medical system factors. CONCLUSIONS: This study indicates
      that underserved Latinas face complex circumstances that interfere with the
      diagnosis and treatment of cancer. However, women expressed positive attitudes
      and held beliefs about survival which helped them through their experience with
      cancer. The implication of these findings is that Latinas have protective
      attitudes and beliefs that help them to overcome "tragic" circumstances.
      Providers need to become aware of the complexity of these issues in order to
      achieve competent, effective, and efficient practice in medical settings with
      Latinas.

PMID- 22418601
TI  - Impact of intra-abdominal pressure on retrohepatic vena cava shape and flow in
      mechanically ventilated pigs.
AB  - Conflicting results have been found regarding correlations between right atrial
      pressure (RAP) and inferior vena cava (IVC) diameter in mechanically ventilated
      patients. This finding could be related to an increase in intra-abdominal
      pressure (IAP). This study was designed to clarify whether variations in IVC flow
      rate caused by positive pressure ventilation are associated with changes in the
      retrohepatic IVC cross-section (DeltaIVC) during major changes in volume status
      and IAP. Nine pigs were anesthetized, mechanically ventilated and equipped. IAP
      was set at 0, 15 and 30 mmHg during two conditions, i.e. normovolemia and
      hypovolemia, generated by blood removal to obtain a mean arterial pressure value
      lower than 60 mmHg. At each IAP increment, cardiac output, IVC flow and surface
      area were respectively assessed by flowmeters and transesophageal
      echocardiography. At normal IAP, even in presence of respiratory changes in IVC
      flows, no DeltaIVC were observed during the two conditions. At high IAP, neither
      DeltaIVC nor modulations of IVC flow were observed whatever the volemic status.
      The majority of animals with an IVC area of less than 0.65 cm(2) showed evidence
      of IAP greater than RAP values. Negative RAP-IAP pressure gradients were found to
      occur with an IVC area of less than 0.65 cm(2), suggesting that IVC dimensions
      determined using standard ultrasound techniques may indicate the direction of the
      RAP-IAP gradient. The clinical relevance of the present findings is that volume
      status should not be estimated from retrohepatic IVC dimensions in cases of high
      IAP.

PMID- 22418602
TI  - Biofilms on environmental surfaces: evaluation of the disinfection efficacy of a
      novel steam vapor system.
AB  - BACKGROUND: Environmental surfaces in health care settings are often contaminated
      by microorganisms, and biofilms can develop on the surfaces in these settings.
      Steam vapor technology is of potential use for disinfection of biofilms on the
      environmental surfaces. METHODS: We tested the disinfection efficacy of a thermal
      accelerated nanocrystal sanitation (TANCS)-equipped steam vapor technology
      against biofilms through disinfecting biofilms developed by 4 bacterial strains
      Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, and
      Staphylococcus aureus-on an identical test surface (ie, polycarbonate) and
      biofilms developed by E coli on 4 different test surfaces: polycarbonate, rubber,
      stainless steel, and ceramics. RESULTS: Our data show that a 3-second steam
      treatment rapidly killed each biofilm tested (>99.95 % killing efficiency). For
      biofilms developed on different surfaces, 3-second steam treatment achieved
      99.95% killing of E coli biofilms developed on different surfaces. Compared with
      chemical disinfection, steam treatment for <1 second a similar level of biofilm
      disinfection as provided by incubation with 10-ppm sodium hypochlorite (bleach)
      for 10-20 minutes of contact time. CONCLUSIONS: Our data suggest that the TANCS
      equipped steam vapor disinfection is an emerging and potentially useful
      technology for disinfecting biofilms on environmental surfaces.

PMID- 22418603
TI  - Computer screen saver hand hygiene information curbs a negative trend in hand
      hygiene behavior.
AB  - BACKGROUND: Appropriate hand hygiene among health care workers is the most
      important infection prevention measure; however, compliance is generally low.
      Gain-framed messages (ie, messages that emphasize the benefits of hand hygiene
      rather than the risks of noncompliance) may be most effective, but have not been
      tested. METHODS: The study was conducted in a 27-bed neonatal intensive care
      unit. We performed an interrupted time series analysis of objectively measured
      hand disinfection events. We used electronic devices in hand alcohol dispensers,
      which continuously documented the frequency of hand disinfection events. In
      addition, hand hygiene compliance before and after the intervention period were
      directly observed. RESULTS: The negative trend in hand hygiene events per patient
      day before the intervention (decrease by 2.3 [standard error, 0.5] per week)
      changed to a significant positive trend (increase of 1.5 [0.5] per week) after
      the intervention (P < .001). The direct observations confirmed these results,
      showing a significant improvement in hand hygiene compliance from 193 of 303
      (63.6%) observed hand hygiene events at pretest to 201 of 281 (71.5%) at
      posttest. CONCLUSIONS: We conclude that gain-framed messages concerning hand
      hygiene presented on screen savers may improve hand hygiene compliance.

PMID- 22418604
TI  - Molecular and epidemiologic predictors of Staphylococcus aureus colonization site
      in a population with limited nosocomial exposure.
AB  - BACKGROUND: The anterior naris has been considered the most consistent location
      of asymptomatic Staphylococcus aureus colonization. However, recent studies have
      shown that a substantial number of individuals, ranging from 7% to 32% of
      colonized individuals, are exclusive throat carriers. Most of these studies have
      been carried out in a health care setting, limiting their generalizability to
      nonhospitalized populations. METHODS: To evaluate anatomic carriage sites of S
      aureus in individuals outside of a health care setting, we combined the results
      of 2 cross-sectional studies conducted in Iowa. RESULTS: S aureus was carried by
      103 of 340 individuals (30.3%), including 31 (30.1%) exclusive throat carriers,
      44 (42.7%) exclusive nose carriers, and 28 (27.2%) colonized in both sites.
      Nonwhite race (adjusted odds ratio [OR], 4.91; 95% confidence interval [CI], 1.26
      18.3) and younger age (>=30 years: OR, 0.23; 95% CI, 0.10-0.54) were associated
      with increased odds of exclusive throat carriage, whereas nonwhite race (OR,
      5.14; 95% CI, 1.62-16.3) and spring or summer sampling season (OR, 2.62; 95% CI,
      1.32-5.18) were associated with increased odds of exclusive nasal carriage.
      CONCLUSIONS: These findings suggest that including a throat swab in addition to a
      nasal swab could play an important role in the success of surveillance programs,
      particularly among younger adults.

PMID- 22418605
TI  - Adherence to international and national recommendations for the prevention of
      surgical site infections in Italy: results from an observational prospective
      study in elective surgery.
AB  - BACKGROUND: An observational prospective study of the perioperative procedures
      for prevention of surgical site infections (SSIs) was carried out in a tertiary
      referral teaching hospital in Liguria, Italy, to evaluate their adherence to
      international and national standards. METHODS: A 1-month survey was performed in
      all surgical departments, monitored by turns by trained survey teams. Data
      regarding presurgical patient preparation and intraoperative infection control
      practices were collected. RESULTS: A total of 717 elective interventions were
      actively monitored in 703 patients who underwent surgery. Hair-shaving was
      performed mainly using a razor (92%) by the nurses (72.8%) on the day before the
      operation (83.5%). All of the patients showered, either with a common detergent
      (87%) or with an antiseptic solution (13%). Antimicrobial prophylaxis was
      administered properly in 75.7% of the patients at induction of anaesthesia;
      however, according to current Italian guidelines, inappropriate prophylaxis was
      provided in 55.2% patients. Appropriate antisepsis of the incision area was done
      in 97.4% of the operations, and nearly 90% of the interventions lasted less than
      the respective 75th percentile. The doors of the operating theatres were mostly
      open during the duration of the operation in 36.3% of the cases. CONCLUSIONS:
      This review of infection control policies identified significant opportunities
      for improving the safety and the quality of routine surgical practice.

PMID- 22418606
TI  - Positive deviance: using a nurse call system to evaluate hand hygiene practices.
AB  - BACKGROUND: Many approaches have been taken to increase compliance with hand
      hygiene by health care professionals. We evaluated a nurse call system used as a
      tool in a positive deviance (PD) approach to improving compliance. METHODS: We
      conducted a quasi-experimental study between September 2008 and December 2010 in
      2 step-down units (SDUs). The consumption of alcohol-based sanitizers for hand
      hygiene was monitored by electronic handwash counters installed in each room as
      of January 2009. The number of nurse visits to patient rooms was measured by the
      nurse call system, which provides information on each instance of nursing care
      provided to the patients. RESULTS: The use of alcohol hand rubs was increased in
      both units after implementation of the PD approach, with higher rates sustained
      for more than 2 years. The rate of device-related infections showed a decreasing
      trend, especially for catheter-associated urinary infection in the east SDU. In
      both units, the ratio of alcohol hand rub uses to nurse visits was >2.5,
      indicating increased use of alcohol rubs, especially in the east SDU, which had a
      ratio of 3 for 2010. CONCLUSIONS: The PD approach to hand hygiene produced
      increased compliance, as measured by increased consumption of alcohol hand
      sanitizer, an improved ratio of alcohol hand rub uses to nurse visits, and a
      reduced rate of device-related infections, with results sustained over 2 years.

PMID- 22418607
TI  - Infection preventionists' job descriptions: do they reflect expanded roles and
      responsibilities?
AB  - In the last decade, the scope of practice of infection preventionists has
      expanded beyond the traditional roles of solo practitioner and expert data
      collectors to roles of interventionists and crucial leaders in successful patient
      safety initiatives. We examined the job descriptions of a small group of
      practicing infection preventionists to determine whether they reflected this
      expanded scope and responsibilities.

PMID- 22418608
TI  - Reduction of surgical site infections in low transverse cesarean section at a
      university hospital.
AB  - BACKGROUND: We implemented evidence-based interventions to reduce risk of
      surgical site infection (SSI) following low transverse cesarean section (LTCS).
      METHODS: An observational study was conducted to determine LTCS SSI rates and the
      impact of infection control interventions at an academic teaching hospital during
      the period October 2005 to December 2008, including the use of 2% chlorhexidine
      gluconate (CHG) for surgical skin preparation before LTCS and no-rinse CHG cloths
      for preoperative skin cleansing. We compared overall and risk strata specific SSI
      rates and standardized incidence ratios during 4 study periods and estimated cost
      savings. RESULTS: Of 1,844 LTCSs performed, 99 patients were identified with SSI.
      SSI rates per 100 LTCS declined from 6.27 at baseline and 10.84 during the
      outbreak period to 5.92 in intervention 1 period and 2.29 in intervention 2
      period. Overall, a 63.5% reduction in SSI rate from baseline was achieved by
      ensuring compliance with SSI prevention guidelines and improving skin antisepsis
      (P = .003). In intervention 2 period, the standardized incidence ratio was 0.99
      compared with 2.64 at baseline and 4.50 during the outbreak period. CONCLUSION: A
      multidisciplinary approach including evidence-based SSI prevention practices,
      effective infection prevention products, and staff and patient engagement
      substantially reduced infection risk and improved patient safety following LTCS.

PMID- 22418609
TI  - Local influenza-like illness surveillance at a university health system during
      the 2009 H1N1 influenza pandemic.
AB  - BACKGROUND: The 2009 novel H1N1 influenza epidemic generated interest in regional
      and national influenza surveillance methods. Some systems revamped traditional
      syndromic and laboratory surveillance techniques, whereas others tracked
      influenza by Internet-based searches or other unique methods. We hypothesized
      that an influenza-like illness (ILI) surveillance system at a single university
      hospital would be accurate and useful for monitoring local influenza activity and
      impact. METHODS: We developed a system of ILI surveillance at 8 sentinel sites
      associated with a university health care system before the pandemic 2009-10
      influenza season. Most sentinel sites used a symptom-based definition of ILI,
      whereas others used electronic medical records-based definitions. RESULTS:
      Results of the local ILI surveillance network correlated well with the onset and
      peak of the influenza season compared with state and regional ILI data, closely
      approximated cases of microbiologically confirmed influenza, demonstrated early
      onset of illness in one site in the sentinel site network, and were available
      several days sooner than data from existing surveillance systems. CONCLUSIONS:
      Local influenza surveillance at a single-institution level provided timely,
      useful, and accurate information, which helped guide resource utilization during
      the pandemic influenza season. The system was an important supplement to state
      and regional influenza surveillance.

PMID- 22418610
TI  - Device-associated nosocomial infection rates in intensive care units at Cairo
      University hospitals: first step toward initiating surveillance programs in a
      resource-limited country.
AB  - BACKGROUND: Device associated infections (DAIs) have major impact on patient
      morbidity and mortality. METHODS: This study involved active prospective
      surveillance to measure the incidence of DAIs, evaluate microbiological profiles,
      and investigate excessive mortality in intensive care units (ICUs) in 3 hospitals
      of Cairo University applying the US Centers for Disease Control and Prevention's
      National Healthcare Safety Network case definitions for ventilator-associated
      pneumonia (VAP), catheter-associated urinary tract infection (CAUTI), and central
      line associated bloodstream infection (CLABSI). Data were collected between March
      2009 and May 2010. RESULTS: A total of 1,101 patients were hospitalized for a
      total of 10,869 days, had 4,734 device-days, and acquired 97 DAIs, with an
      overall rate of 20.5/1,000 ICU days. VAP was the most commonly identified
      infection (88.7%); followed by CLABSI (8.2%) and CAUTI (3.1%). Excess mortality
      was 48% (relative risk, 1.9; P < .001) for CAUTI, 12.9% (relative risk, 1.2; 95%
      confidence interval, 1.1-1.4; P < .05) for VAP, and 45.7% for CLABSI.
      Acinetobacter baumannii was the most frequently isolated pathogen (36.1%),
      followed by Klebsiella pneumoniae (29.2%) and Pseudomonas aeruginosa (22.2%).
      High antimicrobial resistance was identified, with 85% of A baumannii isolates
      resistant to ciprofloxacin and imipenem, 76% of K pneumoniae isolates were
      extended-spectrum beta-lactamase producers, and 56.3% P aeruginosa isolates
      resistant to imipenem (56.3%). CONCLUSION: High rates of DAI and antimicrobial
      resistance require strengthening infection control, instituting surveillance
      systems, and implementing evidence-based preventive strategies.

PMID- 22418611
TI  - Effect of a multidisciplinary intervention on central line utilization in an
      acute care hospital.
AB  - BACKGROUND: Many institutions that have adopted evidence-based infection
      prevention practices have achieved reductions in the rate of central line
      associated bloodstream infection (CLABSI) in their intensive care units (ICUs).
      Few studies have investigated the impact of CLABSI prevention strategies in non
      ICU settings, however. This study was conducted to assess whether a multifaceted
      educational initiative significantly improved health care workers' adherence to
      clinical practices that have been demonstrated to reduce CLABSI rates. METHODS:
      This prospective interventional study compared central line utilization and other
      variables in medical ICU (MICU) and non-ICU settings at an inner city community
      teaching hospital. The study included 3 phases: preintervention, intervention,
      and postintervention. RESULTS: A total of 128 central venous catheter (CVC)
      placements were reviewed. After the intervention, the proportion of patients
      transferred out of the MICU with a CVC in place decreased significantly (P =
      .05), and the percentage of patients transitioned from a CVC to a peripherally
      inserted venous catheter increased (P = .004). The mean duration of CVC use
      decreased from 8.2 days to 5.7 days (P = .004), which was confirmed by linear
      regression (P = .003). CONCLUSIONS: Our data indicate that multidisciplinary,
      evidenced-based educational interventions can significantly improve targeted
      measures of CVC use. Our program was successfully implemented with limited
      resources and should be reproducible at other hospitals.

PMID- 22418612
TI  - Point of care experience with pneumococcal and influenza vaccine documentation
      among persons aged >=65 years: high refusal rates and missing information.
AB  - Missed opportunities to vaccinate and refusal of vaccine by patients have
      hindered the achievement of national health care goals. The meaningful use of
      electronic medical records should improve vaccination rates, but few studies have
      examined the content of these records. In our vaccine intervention program using
      an electronic record with physician prompts, paper prompts, and nursing standing
      orders, we were unable to achieve national vaccine goals, due in large part to
      missing information and patient refusal.

PMID- 22418613
TI  - A paradigm shift in tumour response evaluation of targeted therapy:  the
      assessment of novel drugs in exploratory clinical trials.
AB  - PURPOSE OF REVIEW: To describe the difficulty in assessing the biological
      activity of a novel agent in phase II trials. RECENT FINDINGS: Two major fields
      of research provide interesting new potential endpoints: endpoints based on new
      imaging techniques (e.g. PET or spectral imaging that explore tumour metabolism,
      dynamic contrast enhanced (DCE) ultrasonography or DCE-MRI that explore tumour
      vascularization and tumour growth inhibition) and endpoints integrating
      assessment of tumour burden across time, such as the growth modulation index.
      SUMMARY: Most of the recently described techniques appear attractive, but require
      formal validation.

PMID- 22418614
TI  - Electrical activity of the diaphragm in a small cohort of term neonates.
AB  - BACKGROUND: Electrical activity of the diaphragm (E(di)) has been proposed as a
      parameter to evaluate respiratory function. Normative values of electrical
      activity of the diaphragm in full-term neonates are not known. This is a small
      case series to establish preliminary values  of E(di) in term neonates and to
      determine how these values vary while awake and asleep and during feeding states.
      METHODS: Three term neonates in room air and nippling feeds at the time of the
      study were observed for 4 hours. E(di) was measured by electrodes within a
      nasogastric  tube positioned at the level of the diaphragm. Respiratory rate and
      heart rate were also recorded. Time while awake and asleep were noted. Feeding
      states included feeding, 30 min pre-prandial, and 30 min post-prandial.
      Statistics were analysis of variance and t tests, with P  < .05. RESULTS: Mean
      E(di) peak was 11 +/- 5 MUV. Mean E(di) minimum was 3 +/- 2 MUV. E(di) peak and
      minimum were higher while awake. E(di) peak was lower post-prandial. Respiratory
      rate was higher post-prandial. CONCLUSIONS: These are the  first preliminary
      values for E(di) in neonates. Higher E(di) peak while awake may reflect larger
      tidal volume to meet increased metabolic requirements when awake and active. Post
      prandial lower E(di) peak and higher respiratory rate may indicate compensation
      for  decreased tidal volume from increased intra-abdominal pressure. These data
      may be useful in identifying respiratory pathology in neonates and monitoring
      progression toward respiratory health.

PMID- 22418615
TI  - The arterial supply of the coracoid process.
AB  - OBJECTIVE: The aim of this study was to describe the arterial supply of the
      coracoid process and to define its possible involvement in complications of
      Latarjet procedure. METHOD: Five shoulder dissections were performed to highlight
      the extraosseous blood supply of the coracoid process. Postmortem arteriographies
      of the upper limb were performed. Diaphanization of a scapula enabled to view its
      intraosseous blood supply. RESULTS: The vertical part of coracoid process was
      supplied by supra-scapular artery, and the horizontal part by branches of the
      axillary artery. DISCUSSION AND CONCLUSION: This anatomical study has shown that
      the coracoid process had its own blood supply. During the Latarjet procedure,
      vascular sacrifices are mandatory to allow coracoid process transfer to the
      scapular neck. Such sacrifices could explain lysis or non-union of the coracoid
      process after Latarjet procedure. Preservation of axillary artery branches
      supplying horizontal part of the coracoid process could be a possible solution to
      prevent non-union and lysis of the bone transfer.

PMID- 22418616
TI  - Morphology of the first metatarsal head and hallux rigidus: a cadaveric study.
AB  - PURPOSE: Treatment options for hallux rigidus include several conservative and
      surgical measures. The aetiology leading to the disease has not sufficiently been
      examined so far. MATERIALS AND METHODS: We analysed the anatomical configuration
      of the first metatarsal head of 120 metatarsal bones of different collectives
      aiming to find a possible correlation between the geometry of the first
      metatarsophalangeal joint and manifestation of hallux rigidus. Wet human
      cadaveric specimens and macerated dry specimens served as material. The relevant
      parameters used for analysis were an axis running through the metatarsal head,
      the anatomical longitudinal axis, and the radius of curvature of the first
      metatarsal bone. RESULTS: A significant difference was found in the radius of
      curvature of osteoarthritic and healthy subjects. Using the binary logistic
      regression, we were able to predict the probability of an occurrence of hallux
      rigidus in dependence of the radius of curvature. Furthermore, we were enabled to
      calculate a correct prediction for the appearance of osteoarthritis in 85 % of
      the healthy subjects, and 73 % of the osteoarthritic subjects. CONCLUSIONS: A
      consolidated view of the factors indicates that persons with a high risk for the
      appearance of hallux rigidus should be identified by measuring the radius of
      curvature in conventional radiographs and preventive measures to postpone the
      occurrence of clinically relevant hallux rigidus considered.

PMID- 22418617
TI  - Risk assessment of inferior alveolar neurovascular bundle by multidetector
      computed tomography in extractions of third molars.
AB  - PURPOSE: This study aimed to assess the reliability of multidetector computed
      tomography (MDCT) in determining the surgical risk of the inferior alveolar
      neurovascular bundle in extractions of third molars. METHODS: The sample
      comprised thirty-three individuals (63 third molars) who underwent preoperative
      evaluation by MDCT before extraction of impacted mandibular third molars. MDCT
      was used to determine the relationship between the roots of the third molars and
      the mandibular canal, and the course of the mandibular canal. Inferior alveolar
      nerve (IAN) exposure and the presence of hemorrhage were analyzed after removal
      of the teeth. IAN neurosensory deficit was recorded after 7 days. Clinical and
      MDCT findings were compared using Fisher's exact test (P < 0.05). RESULTS: There
      was a statistically significant association between IAN exposure and the
      tomographic relationship between the roots of third molars and the mandibular
      canal (P = 0.015). Conventionally, all cases of IAN neurosensory deficit and
      hemorrhage occurred when the roots of the third molar presented in an at-risk
      relationship with the mandibular canal, however, this association was not
      statistically significant (P > 0.05). A statistically significant association was
      found between the lingual course of the mandibular canal and IAN exposure (P =
      0.03). CONCLUSIONS: MDCT is an effective tool for determination of the surgical
      risk to the inferior alveolar neurovascular bundle in extraction of mandibular
      third molars.

PMID- 22418618
TI  - A linear-quadratic order parameter coupling model for magnetoelastic phase
      transitions in Fe(1-x)O and MnO.
AB  - The combined structural and antiferromagnetic phase transition in wustite, Fe(1
      x)O, at the Neel temperature, T(N) ~ 195 K, is treated in terms of coupling
      between two macroscopic order parameters related to separate discrete
      instabilities. These each couple with a rhombohedral shear strain to give an
      indirect mechanism of linear (structural)-quadratic (magnetic) coupling between
      them. Based on patterns of lattice parameter and magnetic ordering data from the
      literature, it appears that the overall behaviour matches the general pattern of
      linear-quadratic coupling for a system with two rather similar instability
      temperatures. At low pressures, the magnetic instability occurs at a higher
      temperature than the structural instability but the coupling results in a single
      phase transition dominated by the influence of the magnetic order parameter. For
      Fe(0.99)O the magnetic order parameter, m, varies with temperature as ~m(8) ?
      (T(N) - T), while for Fe(0.94)O the temperature dependence is of ~m(4) or ~m(2).
      It is proposed that, with increasing pressure, there is a crossover of
      instability temperatures such that the structural instability occurs first at
      pressures above ~13 GPa. This would be expected to give rise to a first-order
      phase transition, as appears to occur, but magnetic ordering would still occur
      simultaneously if the coupling is sufficiently strong. Symmetry analysis and
      comparison with the behaviour of MnO shows that there are a number of different
      possible magnetically ordered structures which could be stabilized by pressure or
      non-hydrostatic stress to give topologically rich phase diagrams.

PMID- 22418619
TI  - Body composition in infants: evidence for developmental programming and
      techniques for measurement.
AB  - The consequences of fetal growth retardation remain unclear, in part because they
      appear to vary between industrialized and developing countries. Data on body
      composition offer a new opportunity to investigate this issue, and may be of
      particular value in addressing the controversial role of nutrition in infancy,
      which has been proposed by some to boost survival, and by others to increase long
      term risk of chronic diseases. The uncertainty regarding the effects of post
      natal nutrition is presenting challenges to nutritional policy as many countries
      undergo the nutrition transition, whereby the nutritional status of individuals
      may shift within the life-course. A theoretical model, building on the thrifty
      phenotype hypothesis, is presented to clarify how body composition data can
      address this dilemma. Measurements of body composition can now be obtained in
      infants and children using several different technologies, indicating that large
      scale studies can now be conducted to investigate objectively the association
      between early growth patterns and later health.

PMID- 22418621
TI  - An event-related potential study of maternal love in mothers.
AB  - Feeling is stable and implicit and can be explicated in concrete situations in
      the form of emotion. To map the time course of feeling processing, the present
      study explored electrophysiological responses relevant to inner feeling by
      creating situations to evoke the explicit response of feeling. Fourteen mothers
      were asked to listen to TS and NS. Although the early event-related potential
      components (P1, N1 and P2) elicited by story pictures were not affected by the
      emotional valence of stories, the pictures relevant to TS elicited larger P3 and
      late positive potential (LPP) components than did neutral story pictures,
      indicating that feeling processing occurred at the post-perceptual stage. Feeling
      related positive potential was separated using the difference wave analysis
      technique, which consisted of two sub-components: FRBB1 and FRBB2 based on P3 and
      LPP modulations, respectively. These data provide new electrophysiological
      evidence for the time course of feeling processing related to maternal love.

PMID- 22418620
TI  - Methionine, homocysteine, one carbon metabolism and fetal growth.
AB  - Methionine and folate are the key components of one carbon metabolism, providing
      the methyl groups for numerous methyl transferase reactions via the ubiquitous
      methyl donor, s-adenosyl methionine. Methionine metabolism is responsive to
      nutrient intake, is regulated by several hormones and requires a number of
      vitamins (B12, pyridoxine, riboflavin) as co-factors. The critical relationship
      between perturbations in the mother's methionine metabolism and its impact on
      fetal growth and development is now becoming evident. The relation of folate
      intake to fetal teratogenesis has been known for some time. Studies in human
      pregnancy show a continuous decrease in plasma homocysteine, and an increase in
      plasma choline concentrations with advancing gestation. A higher rate of
      transsulfuration of methionine in early gestation and of transmethylation in the
      3rd trimester was seen in healthy pregnant women. How these processes are
      impacted by nutritional, hormonal and other influences in human pregnancy and
      their effect on fetal growth has not been examined. Isocaloric protein
      restriction in pregnant rats, resulted in fetal growth restriction and metabolic
      reprogramming. Isocaloric protein restriction in the non-pregnant rat, resulted
      in differential expression of a number of genes in the liver, a 50% increase in
      whole body serine biosynthesis and high rate of transmethylation, suggesting high
      methylation demands. These responses were associated with a significant decrease
      in intracellular taurine levels in the liver suggesting a role of cellular
      osmolarity in the observed metabolic responses. These unique changes in
      methionine and one carbon metabolism in response to physiological, nutritional
      and hormonal influences make these processes critical for cellular and organ
      function and growth.

PMID- 22418622
TI  - Genomic evidence of rapid, global-scale gene flow in a Sulfolobus species.
AB  - Local populations of Sulfolobus islandicus diverge genetically with geographical
      separation, and this has been attributed to restricted transfer of propagules
      imposed by the unfavorable spatial distribution of acidic geothermal habitat. We
      tested the generality of genetic divergence with distance in Sulfolobus species
      by analyzing genomes of Sulfolobus acidocaldarius drawn from three populations
      separated by more than 8000 km. In sharp contrast to S. islandicus, the
      geographically diverse S. acidocaldarius genomes proved to be nearly identical.
      We could not link the difference in genome conservation between the two species
      to a corresponding difference in genome stability or ecological factors affecting
      propagule dispersal. The results provide the first evidence that genetic
      isolation of local populations does not result primarily from properties
      intrinsic to Sulfolobus and the severe discontinuity of its geothermal habitat,
      but varies with species, and thus may reflect biotic interactions that act after
      propagule dispersal.

PMID- 22418623
TI  - Distinct and diverse anaerobic bacterial communities in boreal lakes dominated by
      candidate division OD1.
AB  - Lakes have a central role in the carbon cycle of the boreal landscape. These
      systems typically stratify in summer and their hypolimnetic microbial communities
      influence burial of biogenic organic matter in sediments. The composition of
      bacterial communities in these suboxic habitats was studied by pyrosequencing of
      16S rRNA amplicons from five lakes with variable dissolved organic carbon (DOC)
      concentrations. Bacterioplankton communities in the hypolimnetic waters were
      clearly different from the surface layer with candidate division OD1, Chlorobi
      and Bacteroidetes as dominant community members. Several operational taxonomic
      units (OTUs) affiliated with candidate division OD1 were abundant and
      consistently present in the suboxic hypolimnion in these boreal lakes. The
      overall representation of this group was positively correlated with DOC and
      methane concentrations. Network analysis of time-series data revealed contrasting
      temporal patterns but suggested similar ecological roles among the abundant OTUs
      affiliated with candidate division OD1. Together, stable isotope data and
      taxonomic classification point to methane oxidation and autotrophic
      denitrification as important processes in the suboxic zone of boreal lakes. Our
      data revealed that while hypolimnetic bacterial communities are less dynamic,
      they appear to be more diverse than communities from the oxic surface layer. An
      appreciable proportion of the hypolimnetic bacteria belong to poorly described
      phyla.

PMID- 22418624
TI  - Antimicrobial stewardship 2012: science driving practice.

PMID- 22418625
TI  - Policy statement on antimicrobial stewardship by the Society for Healthcare
      Epidemiology of America (SHEA), the Infectious Diseases Society of America
      (IDSA), and the Pediatric Infectious Diseases Society (PIDS).
AB  - Antimicrobial resistance has emerged as a significant healthcare quality and
      patient safety issue in the twenty-first century that, combined with a rapidly
      dwindling antimicrobial armamentarium, has resulted in a critical threat to the
      public health of the United States. Antimicrobial stewardship programs optimize
      antimicrobial use to achieve the best clinical outcomes while minimizing adverse
      events and limiting selective pressures that drive the emergence of resistance
      and may also reduce excessive costs attributable to suboptimal antimicrobial use.
      Therefore, antimicrobial stewardship must be a fiduciary responsibility for all
      healthcare institutions across the continuum of care. This position statement of
      the Society for Healthcare Epidemiology of America, the Infectious Diseases
      Society of America, and the Pediatric Infectious Diseases Society of America
      outlines recommendations for the mandatory implementation of antimicrobial
      stewardship throughout health care, suggests process and outcome measures to
      monitor these interventions, and addresses deficiencies in education and research
      in this field as well as the lack of accurate data on antimicrobial use in the
      United States.

PMID- 22418626
TI  - Antimicrobial stewardship: a collaborative partnership between infection
      preventionists and healthcare epidemiologists.

PMID- 22418627
TI  - Antimicrobial stewardship--the state of the art in 2011: focus on outcome and
      methods.
AB  - Antimicrobial stewardship programs attempt to optimize prescribing of these drugs
      to benefit both current and future patients. Recent regulatory and other
      incentives have led to widespread adoption of such programs. Measurements of the
      success of these programs have focused primarily on process measures. However,
      evaluation of outcome measures will be needed to ensure sustainability of these
      efforts. Outcome efforts to date provide some evidence for improved care of
      individual patients, some evidence for minimizing emergence of resistance, and
      ample evidence for cost reduction. Attention to evaluation methods must be
      increased to provide convincing evidence for the continuation of such programs.

PMID- 22418628
TI  - Antimicrobial stewardship at a large tertiary care academic medical center: cost
      analysis before, during, and after a 7-year program.
AB  - BACKGROUND: An antimicrobial stewardship program was fully implemented at the
      University of Maryland Medical Center in July 2001 (beginning of fiscal year [FY]
      2002). Essential to the program was an antimicrobial monitoring team (AMT)
      consisting of an infectious diseases-trained clinical pharmacist and a part-time
      infectious diseases physician that provided real-time monitoring of antimicrobial
      orders and active intervention and education when necessary. The program
      continued for 7 years and was terminated in order to use the resources to
      increase infectious diseases consults throughout the medical center as an
      alternative mode of stewardship. DESIGN: A descriptive cost analysis before,
      during, and after the program. PATIENTS/SETTING: A large tertiary care teaching
      medical center. METHODS: Monitoring the utilization (dispensing) costs of the
      antimicrobial agents quarterly for each FY. RESULTS: The utilization costs
      decreased from $44,181 per 1,000 patient-days at baseline prior to the full
      implementation of the program (FY 2001) to $23,933 (a 45.8% decrease) by the end
      of the program (FY 2008). There was a reduction of approximately $3 million
      within the first 3 years, much of which was the result of a decrease in the use
      of antifungal agents in the cancer center. After the program was discontinued at
      the end of FY 2008, antimicrobial costs increased from $23,933 to $31,653 per
      1,000 patient-days, a 32.3% increase within 2 years that is equivalent to a $2
      million increase for the medical center, mostly in the antibacterial category.
      CONCLUSIONS: The antimicrobial stewardship program, using an antimicrobial
      monitoring team, was extremely cost effective over this 7-year period.

PMID- 22418629
TI  - Rates and appropriateness of antimicrobial prescribing at an academic children's
      hospital, 2007-2010.
AB  - OBJECTIVE AND DESIGN: Antimicrobial use in hospitalized children has not been
      well described. To identify targets for antimicrobial stewardship interventions,
      we retrospectively examined pediatric utilization rates for 48 antimicrobials
      from 2007 to 2010 as well as appropriateness of vancomycin and cefepime use in
      2010. PATIENTS AND SETTING: All children hospitalized between 2007 and 2010 at
      the Mayo Clinic Children's Hospital, a 120-bed facility within a larger adult
      hospital in Rochester, Minnesota. METHODS: We calculated antimicrobial
      utilization rates in days of therapy per 1,000 patient-days. Details of
      vancomycin and cefepime use in 2010 were abstracted by chart review. Two
      pediatric infectious disease physicians independently assessed appropriateness of
      antibiotic use. RESULTS: From 2007 to 2010, 9,880 of 17,242 (57%) hospitalized
      children received 1 or more antimicrobials. Antimicrobials (days of therapy per
      1,000 patient-days) used most frequently in 2010 were cefazolin (97.8),
      vancomycin (97.1), fluconazole (76.4), piperacillin-tazobactam (70.7), and
      cefepime (67.6). Utilization rates increased significantly from 2007 to 2010 for
      10 antimicrobials, including vancomycin, fluconazole, piperacillin-tazobactam,
      cefepime, trimethoprim-sulfamethoxazole, caspofungin, and cefotaxime. In 2010,
      inappropriate use of vancomycin and cefepime was greater in the pediatric
      intensive care unit than ward (vancomycin: 17.8% vs 6.4%, P = .001; cefepime:
      9.2% vs 3.9%, P = .142) and on surgical versus medical services (vancomycin:
      20.5% vs 8.0%, P = .001; cefepime: 19.4% vs 3.4%, P <= .001). The most common
      reason for inappropriate antibiotic use was failure to discontinue or de-escalate
      therapy. CONCLUSIONS: In our children's hospital, use of 10 antimicrobials
      increased during the study period. Inappropriate use of vancomycin and cefepime
      was greatest on the critical care and surgical services, largely as a result of
      failure to de-escalate therapy, suggesting targets for future antimicrobial
      stewardship interventions.

PMID- 22418630
TI  - Audit and feedback to reduce broad-spectrum antibiotic use among intensive care
      unit patients: a controlled interrupted time series analysis.
AB  - OBJECTIVE: We aimed to rigorously evaluate the impact of prospective audit and
      feedback on broad-spectrum antimicrobial use among critical care patients.
      DESIGN: Prospective, controlled interrupted time series. SETTING: Single tertiary
      care center with 3 intensive care units. PATIENTS AND INTERVENTIONS: A formal
      review of all critical care patients on their third or tenth day of broad
      spectrum antibiotic therapy was conducted, and suggestions for antimicrobial
      optimization were communicated to the critical care team. OUTCOMES: The primary
      outcome was broad-spectrum antibiotic use (days of therapy per 1000 patient-days;
      secondary outcomes included overall antibiotic use, gram-negative bacterial
      susceptibility, nosocomial Clostridium difficile infections, length of stay, and
      mortality. RESULTS: The mean monthly broad-spectrum antibiotic use decreased from
      644 days of therapy per 1,000 patient-days in the preintervention period to 503
      days of therapy per 1,000 patient-days in the postintervention period (P <
      .0001); time series modeling confirmed an immediate decrease (+/- standard error)
      of 119 +/- 37.9 days of therapy per 1,000 patient-days (P = .0054). In contrast,
      no changes were identified in the use of broad-spectrum antibiotics in the
      control group (nonintervention medical and surgical wards) or in the use of
      control medications in critical care (stress ulcer prophylaxis). The incidence of
      nosocomial C. difficile infections decreased from 11 to 6 cases in the study
      intensive care units, whereas the incidence increased from 87 to 116 cases in the
      control wards (P = .04). Overall gram-negative susceptibility to meropenem
      increased in the critical care units. Intensive care unit length of stay and
      mortality did not change. CONCLUSIONS: Institution of a formal prospective audit
      and feedback program appears to be a safe and effective means to improve broad
      spectrum antimicrobial use in critical care.

PMID- 22418631
TI  - Parenteral to oral conversion of fluoroquinolones: low-hanging fruit for
      antimicrobial stewardship programs?
AB  - OBJECTIVE: To estimate avoidable intravenous (IV) fluoroquinolone use in Veterans
      Affairs (VA) hospitals. DESIGN: A retrospective analysis of bar code medication
      administration (BCMA) data. SETTING: Acute care wards of 128 VA hospitals
      throughout the United States. METHODS: Data were analyzed for all medications
      administered on acute care wards between January 1, 2006, and December 31, 2010.
      Patient-days receiving therapy were expressed as fluoroquinolone-days (FD) and
      divided into intravenous (IV; all doses administered intravenously) and oral (PO;
      at least one dose administered per os) FD. We assumed IV fluoroquinolone use to
      be potentially avoidable on a given IV FD when there was at least 1 other
      medication administered via the enteral route. RESULTS: Over the entire study
      period, 884,740 IV and 830,572 PO FD were administered. Overall, avoidable IV
      fluoroquinolone use accounted for 46.8% of all FD and 90.9% of IV FD. Excluding
      the first 2 days of all IV fluoroquinolone courses and limiting the analysis to
      the non-ICU setting yielded more conservative estimates of avoidable IV use:
      20.9% of all FD and 45.9% of IV FD. Avoidable IV use was more common for
      levofloxacin and more frequent in the ICU setting. There was a moderate
      correlation between avoidable IV FD and total systemic antibiotic use (r = 0.32).
      CONCLUSIONS: Unnecessary IV fluoroquinolone use seems to be common in the VA
      system, but important variations exist between facilities. Antibiotic stewardship
      programs could focus on this patient safety issue as a "low-hanging fruit" to
      increase awareness of appropriate antibiotic use.

PMID- 22418632
TI  - Decreased resistance of Pseudomonas aeruginosa with restriction of ciprofloxacin
      in a large teaching hospital's intensive care and intermediate care units.
AB  - OBJECTIVE: To examine the effect of restricting ciprofloxacin on the resistance
      of nosocomial gram-negative bacilli, including Pseudomonas aeruginosa, to
      antipseudomonal carbapenems. DESIGN: Interrupted time-series analysis. SETTING:
      Tertiary care teaching hospital with 11 intensive care and intermediate care
      units with a total of 295 beds. PATIENTS: All nosocomial isolates of P.
      aeruginosa. INTERVENTION: Restriction of ciprofloxacin. RESULTS: There was a
      significant decreasing trend observed in the percentage (P = .0351) and the rate
      (P = .0006) of isolates of P. aeruginosa that were resistant to antipseudomonal
      carbapenems following the restriction of ciprofloxacin. There was also a
      significant decreasing trend observed in the percentage (P = .0017) and the rate
      (P = .0001) of isolates of ciprofloxacin-resistant P. aeruginosa. The rate of
      cefepime-resistant P. aeruginosa isolates declined (P = .004) but the percentage
      of cefepime-resistant P. aeruginosa isolates did not change. There were no
      significant changes observed in the rate or the percentage of piperacillin
      tazobactam-resistant P. aeruginosa isolates. There were no significant changes
      observed in the susceptibilities of nosocomial Enterobacteriaciae or
      Acinetobacter baumannii isolates that were resistant to carbapenems. Over the
      study period there was a significant increase in the use of carbapenems (P =
      .0134); the use of ciprofloxacin decreased significantly (P = .0027). There were
      no significant changes in the use of piperacillin-tazobactam or cefepime.
      CONCLUSION: Restriction of ciprofloxacin was associated with a decreased
      resistance of P. aeruginosa isolates to antipseudomonal carbapenems and
      ciprofloxacin in our hospital's intermediate care and intensive care units. There
      were no changes observed in the susceptibilities of nosocomial Enterobacteriaciae
      or A. baumannii to carbapenems, despite increased carbapenem use. Reducing
      ciprofloxacin use may be a means of controlling multidrug-resistant P.
      aeruginosa.

PMID- 22418633
TI  - Evaluation of postprescription review and feedback as a method of promoting
      rational antimicrobial use: a multicenter intervention.
AB  - OBJECTIVE: To evaluate the impact of postprescription review of broad-spectrum
      antimicrobial (study-ABX) agents on rates of antimicrobial use. DESIGN: Quasi
      experimental before-after study. SETTING: Five academic medical centers.
      PATIENTS: Adults receiving at least 48 hours of study-ABX. METHODS: The baseline,
      intervention, and follow-up periods were 6 months each in 2 units at each of 5
      sites. Adults receiving at least 48 hours of study-ABX entered the cohort as case
      patients. During the intervention, infectious-diseases physicians reviewed the
      cases after 48 hours of study-ABX. The provider was contacted with alternative
      recommendations if antimicrobial use was considered to be unjustified on the
      basis of predetermined criteria. Acceptance rates were assessed 48 hours later.
      The primary outcome measure was days of study-ABX per 1,000 study-patient-days in
      the baseline and intervention periods. RESULTS: There were 1,265 patients in the
      baseline period and 1,163 patients in the intervention period. Study-ABX use
      decreased significantly during the intervention period at 2 sites: from 574.4 to
      533.8 study-ABX days/1,000 patient-days (incidence rate ratio [IRR], 0.93; 95%
      confidence interval [CI], 0.88-0.97; P = .002) at hospital B and from 615.6 to
      514.4 study-ABX days/1,000 patient-days (IRR, 0.83; 95% CI, 0.79-0.88; P < .001)
      at hospital D. Both had established antimicrobial stewardship programs (ASP).
      Study-ABX use increased at 2 sites and stayed the same at 1 site. At all
      institutions combined, 390 of 1,429 (27.3%) study-ABX courses were assessed as
      unjustified; recommendations to modify or stop therapy were accepted for 260
      (66.7%) of these courses. CONCLUSIONS: Postprescription review of study-ABX
      decreased antimicrobial utilization in some of the study hospitals and may be
      more effective when performed as part of an established ASP.

PMID- 22418634
TI  - Demonstration of the weighted-incidence syndromic combination antibiogram: an
      empiric prescribing decision aid.
AB  - OBJECTIVE: Healthcare providers need a better empiric antibiotic prescribing aid
      than the traditional antibiogram, which supplies no information on the relative
      frequency of organisms recovered in a given infection and which is uninformative
      in situations where multiple antimicrobials are used or multiple organisms are
      anticipated. We aimed to develop and demonstrate a novel empiric prescribing
      decision aid. DESIGN/SETTING: This is a demonstration involving more than 9,000
      unique encounters for abdominal-biliary infection (ABI) and urinary tract
      infection (UTI) to a large healthcare system with a fully integrated electronic
      health record (EHR). METHODS: We developed a novel method of displaying
      microbiology data called the weighted-incidence syndromic combination antibiogram
      (WISCA) for 2 clinical syndromes, ABI and UTI. The WISCA combines simple
      diagnosis and microbiology data from the EHR to (1) classify patients by syndrome
      and (2) determine, for each patient with a given syndrome, whether a given
      regimen (1 or more agents) would have covered all the organisms recovered for
      their infection. This allows data to be presented such that clinicians can see
      the probability that a particular regimen will cover a particular infection
      rather than the probability that a single drug will cover a single organism.
      RESULTS: There were 997 encounters for ABI and 8,232 for UTI. A WISCA was created
      for each syndrome and compared with a traditional antibiogram for the same
      period. CONCLUSIONS: Novel approaches to data compilation and display can
      overcome limitations to the utility of the traditional antibiogram in helping
      providers choose empiric antibiotics.

PMID- 22418635
TI  - The economics of antimicrobial stewardship: the current state of the art and
      applying the business case model.

PMID- 22418636
TI  - Show me the money: long-term financial impact of an antimicrobial stewardship
      program.
AB  - The financial impact of an antimicrobial stewardship program in operation for
      more than 11 years was determined by calculating the reduction in antimicrobial
      expenditures minus program labor costs. Depending on the method of inflation
      adjustment used, the program was associated with average cost savings of $920,070
      to $2,064,441 per year.

PMID- 22418637
TI  - Antimicrobial stewardship at transition of care from hospital to community.
AB  - Mandatory infectious disease consultation for parenteral antimicrobials at
      hospital discharge resulted in avoiding postdischarge parenteral antimicrobials
      in 28% of patients. No emergency department visit or rehospitalization within 30
      days for these patients was a consequence of parenteral antimicrobial avoidance.
      Antimicrobial stewardship at transition of care is effective in reducing
      unnecessary antimicrobial use.

PMID- 22418638
TI  - Implementation of an antimicrobial stewardship program at a 60-bed long-term
      acute care hospital.
AB  - We implemented an antimicrobial stewardship program at an urban, 60-bed long-term
      acute care hospital using a strategy of weekly postprescriptive chart audit with
      intervention and feedback. The results for the first 15 months demonstrated 80%
      acceptance of recommendations, a 21% reduction in use, and a 28% reduction in
      cost per patient-day.

PMID- 22418640
TI  - Implementation of a clinical decision support system for antimicrobial
      stewardship.
AB  - Clinical decision support systems (CDSSs) for antimicrobial stewardship require
      considerable human resources and financial investments. This pre
      /postimplementation study evaluated the effect of a CDSS on performance of
      prospective audit with intervention and feedback and demonstrated an increase in
      interventions and recommendation acceptance countered by a substantial number of
      nonactionable alerts.

PMID- 22418639
TI  - Comparative assessment of antimicrobial usage measures in the Department of
      Veterans Affairs.
AB  - We compared 2 data sources--antimicrobial orders and bar-coded medication
      administration (BCMA)--for calculating the number of grams used, grams used based
      on defined daily dose, and days of therapy at one Veterans Affairs Medical Center
      for 2009-2010. The number of grams used calculated from BCMA data provided the
      most informative antimicrobial utilization measure.

PMID- 22418641
TI  - Constructing unit-specific empiric treatment guidelines for catheter-related and
      primary bacteremia by determining the likelihood of inadequate therapy.
AB  - This study aimed to determine the feasibility of using likelihood of inadequate
      therapy (LIT), a parameter calculated by using pathogen frequency and in vitro
      susceptibility for determination of appropriate empiric antibiotic therapy for
      primary bloodstream infections. Our study demonstrates that LIT may reveal
      differences in traditional antibiograms.

PMID- 22418642
TI  - Lack of significant variability among different methods for calculating
      antimicrobial days of therapy.
AB  - Days of therapy (DOTs) are an important measure to quantify antimicrobial use but
      may not reflect patients' true antimicrobial exposure. Three methods of
      calculating DOTs were compared to determine whether including "exposure days,"
      when antimicrobials are given less frequently than daily due to renal
      dysfunction, makes a difference.

PMID- 22418643
TI  - Impact of the use of procalcitonin assay in hospitalized adult patients with
      pneumonia at a community acute care hospital.
AB  - A retrospective, quasi-experimental cohort study compared antibiotic use before
      and after implementation of a procalcitonin assay at a community acute care
      hospital. This study demonstrated that the implementation of the procalcitonin
      assay was associated with a decrease in antibiotic days of therapy in adult
      patients with pneumonia.

PMID- 22418644
TI  - Antibiotic stewardship for intra-abdominal infections: early impact on
      antimicrobial use and patient outcomes.

PMID- 22418645
TI  - Attitudes of housestaff toward a prior-authorization-based antibiotic stewardship
      program.

PMID- 22418646
TI  - An examination of stewardship interventions by major category in an urban
      academic medical center.

PMID- 22418647
TI  - The impact of an infectious diseases specialist-directed computerized physician
      order entry antimicrobial stewardship program targeting linezolid use.

PMID- 22418648
TI  - A computer-assisted prescription system to improve antibacterial surgical
      prophylaxis.

PMID- 22418649
TI  - Patient satisfaction and suggestions for improvement of remote ICD monitoring.
AB  - PURPOSE: The study aim was to evaluate patient acceptance and content with remote
      follow-up (FU) of their implantable cardioverter defibrillator (ICD) and to
      estimate patients' wish for changes in remote follow-up routines. METHODS: Four
      hundred seventy-four ICD patients at the device follow-up clinic at
      Rigshospitalet using CareLink(r) (Medtronic) remote follow-up, who had made >=2
      transmissions, received a questionnaire. RESULTS: Three hundred eighty-five
      patients (81.2%) answered. Mean time with ICD was 56 +/- 45 months and mean age
      was 62 +/- 13 years; 80% was male. Diagnosis related to ICD implant was: ischemic
      heart disease in 56% and dilated cardiomyopathy in 21%. Twenty-six percent had
      primary prophylactic indication. Mean time on remote FU was 16.4 +/- 6.9 months.
      Mean time spent on in-clinic FU (two-way transport and FU) was 4 h and 36 min +/-
      7 h and 50 min, excluding 12 patients from Greenland and Faroe Islands. Ninety
      five percent of the patients was very content or content with remote FU compared
      to in-clinic FU; 3% was less content and 2% was not content. For scheduled
      transmissions, 21% of the patients wished for a faster reply (sms or e-mail)
      compared to current practice with a letter. Eighty-four percent preferred more
      detailed information concerning ICD leads, battery status, and ICD therapies. A
      total of 96 patients (25%) had performed extra unscheduled remote transmissions:
      20 due to shock, 20 due to alarm, 35 due to palpitations, and 18 for other or
      combined reasons. CONCLUSION: Ninety-five percent of the patients were content
      with the remote FU. Only 25% had unscheduled transmissions and most unscheduled
      transmissions were for appropriate reasons. Eighty-four percent of the patients
      wished for a more detailed response and 21% wished for a faster reply after
      routine transmissions.

PMID- 22418650
TI  - Pyrethroid insecticides in bed sediments from urban and agricultural streams
      across the United States.
AB  - Pyrethroid insecticides are hydrophobic compounds that partition to streambed
      sediments and have been shown to cause toxicity to non-target organisms; their
      occurrence is well documented in parts of California, but there have been limited
      studies in other urban and agricultural areas across the United States. To
      broaden geographic understanding of pyrethroid distributions, bed sediment
      samples were collected and analyzed from 36 streams in 25 states, with about 2/3
      of the sites in urban areas and 1/3 in agricultural areas. At least one
      pyrethroid (of the 14 included in the analysis) was detected in 78% of samples.
      Seven pyrethroids were detected in one or more samples. Bifenthrin was the most
      frequently detected (58% of samples), followed by permethrin (31%), resmethrin
      (17%), and cyfluthrin (14%). The other three detected pyrethroids (cyhalothrin,
      cypermethrin and delta/tralomethrin) were found in two or fewer of the samples.
      Concentrations ranged from 0.3 to 180 ng g(-1) dry weight. The number of
      pyrethroids detected were higher in the urban samples than in the agricultural
      samples, but the highest concentrations of individual pyrethroids were split
      between urban and agricultural sites. The pyrethroids detected in the
      agricultural areas generally followed use patterns. Predicted toxicity was
      greater for urban areas and attributed to bifenthrin, cyfluthrin and
      cypermethrin, while in agricultural areas the toxicity was mainly attributed to
      bifenthrin.

PMID- 22418651
TI  - Global air quality and health co-benefits of mitigating near-term climate change
      through methane and black carbon emission controls.
AB  - BACKGROUND: Tropospheric ozone and black carbon (BC), a component of fine
      particulate matter (PM <= 2.5 um in aerodynamic diameter; PM(2.5)), are
      associated with premature mortality and they disrupt global and regional climate.
      OBJECTIVES: We examined the air quality and health benefits of 14 specific
      emission control measures targeting BC and methane, an ozone precursor, that were
      selected because of their potential to reduce the rate of climate change over the
      next 20-40 years. METHODS: We simulated the impacts of mitigation measures on
      outdoor concentrations of PM(2.5) and ozone using two composition-climate models,
      and calculated associated changes in premature PM(2.5)- and ozone-related deaths
      using epidemiologically derived concentration-response functions. RESULTS: We
      estimated that, for PM(2.5) and ozone, respectively, fully implementing these
      measures could reduce global population-weighted average surface concentrations
      by 23-34% and 7-17% and avoid 0.6-4.4 and 0.04-0.52 million annual premature
      deaths globally in 2030. More than 80% of the health benefits are estimated to
      occur in Asia. We estimated that BC mitigation measures would achieve
      approximately 98% of the deaths that would be avoided if all BC and methane
      mitigation measures were implemented, due to reduced BC and associated reductions
      of nonmethane ozone precursor and organic carbon emissions as well as stronger
      mortality relationships for PM(2.5) relative to ozone. Although subject to large
      uncertainty, these estimates and conclusions are not strongly dependent on
      assumptions for the concentration-response function. CONCLUSIONS: In addition to
      climate benefits, our findings indicate that the methane and BC emission control
      measures would have substantial co-benefits for air quality and public health
      worldwide, potentially reversing trends of increasing air pollution
      concentrations and mortality in Africa and South, West, and Central Asia. These
      projected benefits are independent of carbon dioxide mitigation measures.
      Benefits of BC measures are underestimated because we did not account for
      benefits from reduced indoor exposures and because outdoor exposure estimates
      were limited by model spatial resolution.

PMID- 22418654
TI  - 29th ESPID Annual Meeting in The Hague, the Netherlands.

PMID- 22418653
TI  - Challenges in estimating the impact of pneumococcal conjugate vaccines through
      surveillance.

PMID- 22418655
TI  - Twelve-year-old female with short bowel syndrome presents with dizziness and
      confusion.

PMID- 22418656
TI  - Challenges in estimating efficacy against pneumococcal pneumonia in children.

PMID- 22418658
TI  - Acute cerebellitis and concurrent encephalitis associated with parvovirus B19
      infection.

PMID- 22418659
TI  - Primary cutaneous aspergillosis in two pediatric trauma patients.

PMID- 22418660
TI  - Denouement.

PMID- 22418661
TI  - Identification of antigen and adjuvant doses resulting in optimal immunogenicity
      and antibody persistence up to 1 year after immunization with a pandemic A/H1N1
      influenza vaccine in children 3 to < 9 years of age.
AB  - BACKGROUND: In the development of pediatric A/H1N1 influenza vaccines, this study
      was performed to identify antigen and adjuvant doses providing optimal
      immunogenicity and antibody persistence to ensure long-term immunity after
      immunization with an adjuvanted A/H1N1 vaccine in children 3 to <9 years of age.
      METHODS: Healthy children (N = 1357) were immunized with 1 of 8 investigational
      vaccine formulations ranging in antigen (3.75-30 ug) and MF59 adjuvant (Novartis
      Vaccines, Marburg, Germany; 0, 50 and 100% of standard dose). Each participant
      received 2 vaccine doses given 3 weeks apart. Immunogenicity was analyzed by
      hemagglutination inhibition assay in sera drawn 3, 4 and 6 weeks after first
      vaccination. Long-term antibody persistence was assessed 6 and 12 months after
      immunization. Vaccine safety was monitored throughout the study. RESULTS: All
      MF59-adjuvanted vaccines were well tolerated and highly immunogenic, with
      adjuvanted formulations inducing antibody titers statistically superior to those
      of the nonadjuvanted vaccines. Each MF59-adjuvanted vaccine met all the US and
      European licensure criteria for influenza vaccines 3 weeks after the
      administration of a single dose; all nonadjuvanted formulations failed to meet
      licensure criteria at this time point. Antibody titers in response to a single
      vaccination with 7.5 ug antigen and a full dose of MF59 continued to meet all US
      and European licensure criteria up to 1 year after immunization. CONCLUSION: A
      single dose of vaccine containing 7.5 ug A/California/7/2009 (H1N1) antigen and a
      full dose of MF59 adjuvant was found to be optimal for children 3 to <9 years of
      age.

PMID- 22418663
TI  - An efficient synthetic method for allyl-epoxides via allylation of alpha
      haloketones or esters with allylmagnesium bromide.
AB  - A simple, efficient, and non-metal-catalyzed synthetic method for allyl-epoxides
      and diallyl-epoxides by allylation of alpha-haloketones and esters with
      allylmagnesium bromide in mild conditions is reported in this article. It
      inherited some advantages of the organomagnesium reagents such as availability,
      operational simplicity and low toxicity.

PMID- 22418662
TI  - Evaluation of haemophilus influenzae type b vaccine for routine immunization in
      Nepali infants.
AB  - BACKGROUND: Haemophilus influenzae type b (Hib) carriage and disease studies in
      Nepali children suggest a significant burden of infection. Hib conjugate vaccines
      (HibCV) do not have uniform immunogenicity between populations. We determined the
      immunogenicity of HibCV in Nepali infants, before its introduction into the
      routine immunization schedule. METHODS: Ninety infants recruited at Patan
      Hospital, Kathmandu, received 3 doses of the HibCV with routine immunizations
      (diphtheria, tetanus, whole cell pertussis-hepatitis B vaccine + oral polio
      vaccine) at 6, 10 and 14 weeks of age, and a HibCV booster at 52 weeks. Anti
      polyribosylribitol phosphate (PRP) concentrations were measured at 18, 52 and 56
      weeks, and the antibody persistence at 52 weeks was compared with antibody values
      in unimmunized controls (n = 30). RESULTS: After 3 doses of primary
      immunizations, at 18 weeks of age (n = 74), all infants had anti-PRP
      concentrations above the accepted thresholds for short- and long-term protection
      (0.15 and 1.0 ug/mL, respectively). At 1 year of age, before administration of
      the booster of HibCV, the anti-PRP geometric mean antibody concentration was 2.76
      ug/mL (confidence interval: 1.88-4.07) in sera from the immunized children
      compared with 0.11 ug/mL (95% confidence interval: 0.08-0.17) in the nonimmunized
      control group (n = 30). Twenty-seven percent (20/74) of participants, however,
      had anti-PRP concentrations <1.0 ug/mL. Four weeks after the booster dose of
      HibCV, 98.5% of infants had anti-PRP concentrations above 1.0 ug/mL. CONCLUSION:
      Immunization with HibCV given as part of the Expanded Program on Immunization
      schedule in Nepal elicits robust antibody responses. Though the antibody wanes
      during the first year of life, most 1-year-old infants remain protected and
      respond robustly to a booster dose of the vaccine.

PMID- 22418664
TI  - Electromagnetic simulations of a photonic luminescent solar concentrator.
AB  - Luminescent solar concentrators (LSC) are used in photovoltaic applications to
      concentrate direct and diffuse sunlight without tracking. We employed 2D FDTD
      simulations to investigate the concept of a photonic LSC (PLSC), where the
      luminescent material is embedded in a photonic crystal to mitigate the primary
      losses in LSCs: the escape cone and reabsorption. We obtain suppressed emission
      inside the photonic band gap, which can be utilized to reduce reabsorption.
      Furthermore, the efficiency of light guiding is strongly enhanced in a broad
      spectral range, reaching up to 99.7%. Our optimization of design parameters
      suggests emitting layers of sub-wavelength thickness.

PMID- 22418665
TI  - Enhanced optical absorption of dye-sensitized solar cells with microcavity
      embedded TiO2 photoanodes.
AB  - This paper reports the enhanced performance of dye-sensitized solar cells (DSSCs)
      with microcavity-embedded nanoporous TiO2 photoanodes. For DSSCs with photoanodes
      composed of a stack TiO2 sublayers with microcavity concentrations arranged from
      low to high on the light illumination path, the short-circuit current density and
      the conversion efficiency were improved. A pronounced increase in optical
      absorption and incident monochromatic photon-to-current conversion efficiency in
      the long-wavelength region indicated that the enhancement of cell performance was
      due to the multiple scattering of light by the microcavities and the light
      confinement by the stack of TiO2 sublayers with a high-to-low effective index of
      refraction.

PMID- 22418666
TI  - Highly absorbing solar cells--a survey of plasmonic nanostructures.
AB  - Plasmonic light trapping in thin film solar cells is investigated using full-wave
      electromagnetic simulations. Light absorption in the semiconductor layer with
      three standard plasmonic solar cell geometries is compared to absorption in a
      flat layer. We identify near-field absorption enhancement due to the excitation
      of localized surface plasmons but find that it is not necessary for strong light
      trapping in these configurations: significant enhancements are also found if the
      real metal is replaced by a perfect conductor, where scattering is the only
      available enhancement mechanism. The absorption in a 60 nm thick organic
      semiconductor film is found to be enhanced by up to 19% using dispersed silver
      nanoparticles, and up to 13% using a nanostructured electrode. External in
      scattering nanoparticles strongly limit semiconductor absorption via back
      reflection.

PMID- 22418667
TI  - Immersed finger-type indium tin oxide ohmic contacts on p-GaN photoelectrodes for
      photoelectrochemical hydrogen generation.
AB  - In this study, we demonstrated photoelectrochemical (PEC) hydrogen generation
      using p-GaN photoelectrodes associated with immersed finger-type indium tin oxide
      (IF-ITO) ohmic contacts. The IF-ITO/p-GaN photoelectrode scheme exhibits higher
      photocurrent and gas generation rate compared with p-GaN photoelectrodes without
      IF-ITO ohmic contacts. In addition, the critical external bias for detectable
      hydrogen generation can be effectively reduced by the use of IF-ITO ohmic
      contacts. This finding can be attributed to the greatly uniform distribution of
      the IF-ITO/p-GaN photoelectrode applied fields over the whole working area. As a
      result, the collection efficiency of photo-generated holes by electrode contacts
      is higher than that of p-GaN photoelectrodes without IF-ITO contacts. Microscopy
      revealed a tiny change on the p-GaN surfaces before and after hydrogen
      generation. In contrast, photoelectrodes composed of n-GaN have a short lifetime
      due to n-GaN corrosion during hydrogen generation. Findings of this study
      indicate that the ITO finger contacts on p-GaN layer is a potential candidate as
      photoelectrodes for PEC hydrogen generation.

PMID- 22418668
TI  - Absorption coefficient modeling of microcrystalline silicon thin film using
      Maxwell-Garnett effective medium theory.
AB  - Considering the Mott-Davis density of state model and Rayleigh scattering effect,
      we present an approach to model the absorption profile of microcrystalline
      silicon thin films in this paper. Maxwell-Garnett effective medium theory was
      applied to analyze the absorption curves. To validate the model, several
      experimental profiles have been established and compared with those results from
      the model. With the assistance of the genetic algorithm, our results show that
      the absorption curves from the model are in good agreement with the experiments.
      Our findings also indicate that, as the crystal volume fraction increases, not
      only do the defects in amorphous silicon reduce, but the bulk scattering effect
      is gradually enhanced as well.

PMID- 22418669
TI  - Extraction of surface plasmons in organic light-emitting diodes via high-index
      coupling.
AB  - The efficiency of organic light-emitting diodes (OLEDs) is still limited by poor
      light outcoupling. In particular, the excitation of surface plasmon polaritons
      (SPPs) at metal-organic interfaces represents a major loss channel. By combining
      optical simulations and experiments on simplified luminescent thin-film
      structures we elaborate the conditions for the extraction of SPPs via coupling to
      high-index media. As a proof-of-concept, we demonstrate the possibility to
      extract light from wave-guided modes and surface plasmons in a top-emitting white
      OLED by a high-index prism.

PMID- 22418670
TI  - High power efficiency phosphorescent poly(dendrimer) OLEDs.
AB  - We show that it is possible to produce an efficient solution-processable
      phosphorescent poly(dendrimer) OLED with a 32 lm/W power efficiency at 100 cd/m2
      without using a charge transporting host or any improvements in light extraction.
      This is achieved by using the dendrimer architecture to control inter-chromophore
      interactions. The effects of using 4,4',4"-tris(N-carbazolyl)triphenylamine
      (TCTA) as a charge transporting host and using a double dendron structure to
      further reduce inter-chromophore interactions are also reported.

PMID- 22418671
TI  - Multi-layer printing of OLEDs as a tool for the creation of security features.
AB  - The combined deposition of structured and homogenous layers for the device setup
      of OLEDs results in a structured display visible with a gray scale impression.
      These permanently imprinted structures are only visible during the application of
      an electrical field and almost invisible in the off state. Most intriguing
      applications of such devices are security marks, electronic watermarks but also
      for advertising and design applications the creation of gray scale structures
      might have interesting applications.

PMID- 22418672
TI  - Photonic light-trapping versus Lambertian limits in thin film silicon solar cells
      with 1D and 2D periodic patterns.
AB  - We theoretically investigate the light-trapping properties of one- and two
      dimensional periodic patterns etched on the front surface of c-Si and a-Si thin
      film solar cells with a silver back reflector and an anti-reflection coating. For
      each active material and configuration, absorbance A and short-circuit current
      density Jsc are calculated by means of rigorous coupled wave analysis (RCWA), for
      different active materials thicknesses in the range of interest of thin film
      solar cells and in a wide range of geometrical parameters. The results are then
      compared with Lambertian limits to light-trapping for the case of zero absorption
      and for the general case of finite absorption in the active material. With a
      proper optimization, patterns can give substantial absorption enhancement,
      especially for 2D patterns and for thinner cells. The effects of the photonic
      patterns on light harvesting are investigated from the optical spectra of the
      optimized configurations. We focus on the main physical effects of patterning,
      namely a reduction of reflection losses (better impedance matching conditions),
      diffraction of light in air or inside the cell, and coupling of incident
      radiation into quasi-guided optical modes of the structure, which is
      characteristic of photonic light-trapping.

PMID- 22418673
TI  - Multispectral mixing scheme for LED clusters with extended operational
      temperature window.
AB  - LEDs have changed the concept of illumination not only in an expectation of the
      highest electroluminance efficiency but also in tremendous chances for smart
      lighting applications. With a cluster mixing, many studies were addressed to
      strategically manipulate the chromaticity point, system efficiency and color
      rendering performance according to different operational purposes. In this paper,
      we add an additional thermal function to extend the operational thermal window of
      a pentachromatic R/G/B/A/CW light engine over a chromaticity from 2800K to 8000K.
      The proposed model is experimentally validated to offer a full operable range in
      ambient temperature (Ta = 10 degrees  to 100 degrees C) associated with high
      color quality scale (above 85 points) as well as high luminous efficiency (above
      100 lm/watt).

PMID- 22418674
TI  - Photon management with core-shell nanowire structures.
AB  - Antireflective Si/oxide core-shell nanowire arrays (NWAs) were fabricated by
      galvanic etching and subsequent annealing process. The excellent light-harvesting
      characteristics of the core-shell NWAs, such as broadband working ranges,
      omnidirectionality, and polarization-insensitivity, ascribed to the smooth index
      transition from air to the substrates, have been demonstrated. By tuning core
      shell volume ratios, we obtained enhanced light trapping regions implemented in
      either the planar Si underneath NWAs or the core regions of NWAs, greatly
      benefiting the geometry design of planar and radial p-n junction cell structures,
      respectively. This photon management scheme indicates the potential use in
      nanostructured photovoltaic applications.

PMID- 22418675
TI  - Angular selective semi-transparent photovoltaics.
AB  - Conventional semi-transparent photovoltaics suffer from an inherent tradeoff
      between the amount of visible light transmitted versus absorbed, reducing energy
      conversion efficiency when higher transparency is desired. As a solution to lift
      this tradeoff, we propose a wavelength and angular selective reflector and
      demonstrate a potential implementation utilizing high aspect ratio metal
      nanoparticles. Using the anisotropy in the localized surface plasmon resonance
      wavelength, the proposed device can selectively harness sunlight incident at an
      elevated angle, increasing the power conversion efficiency by a factor of 1.44,
      while maintaining 70 percent optical transparency at normal incidence.

PMID- 22418676
TI  - Light-emitting devices with tunable color from ZnO nanorods grown on InGaN/GaN
      multiple quantum wells.
AB  - Based on the composite consisting of ZnO nanorods (NRs) grown on InGaN/GaN
      multiple quantum wells (MQWs), we have demonstrated a novel light-emitting device
      (LED) that has the capability to emit dual beam radiations. Interestingly, the
      relative intensity between the dual emissions is able to be manipulated by their
      polarizations. The underlying mechanism can be well understood in terms of the
      anisotropic optical properties arising from the geometric structures of
      constituent nanoscale materials. The results shown here may be extended to many
      other nanocomposite systems and pave a new pathway to create LEDs with tunable
      properties.

PMID- 22418677
TI  - Reflective type Solar-LCDs by using polarizing polymer solar cells.
AB  - We present herein the results of a study of the reflective polarizing
      photovoltaic (PV) effects in an aligned polymer bulk-heterojunction PV layer. The
      PV layer consisted of a composite of regioregular poly(3-hexylthiophene) and
      methanofullerene (P3HT:PCBM) and the fairly uniform in-plane alignment of the
      P3HT:PCBM PV layer was achieved by means of a simple rubbing technique. The
      macroscopic axial orientation of the P3HT polymer in the aligned PV layer was
      observed to be significantly increased in the direction of rubbing with an axial
      orientational order parameter of 0.40. Moreover, it was also found that the
      reflective polarizing polymer solar cells (PSCs) that contained the aligned
      P3HT:PCBM layers exhibited a greater degree of anisotropy of 1.60 for the PV
      efficiencies under polarized illumination along the two principal axes. These
      reflective polarizing PSCs were applied to new reflective type solar cell-liquid
      crystal displays (Solar-LCDs), which exhibited a contrast ratio of 1.7. These
      results form a promising foundation for various energy-harvesting polarization
      dependent opto-electrical Solar-LCD device applications.

PMID- 22418678
TI  - Enhancement of wall-plug efficiency in vertical InGaN/GaN LEDs by improved
      current spreading.
AB  - We present the enhancement of wall-plug efficiency in vertical InGaN/GaN light
      emitting diodes (V-LEDs) by improved current spreading with a novel Al2O3 current
      blocking layer (CBL). The Al2O3 CBL deposited by electron-beam evaporation shows
      high transmittance and good corrosion resistance to acidic solutions. V-LEDs with
      an Al2O3 CBL show similar light output power but lower forward voltage as
      compared to those with a SiO2 CBL deposited by plasma-enhanced chemical vapor
      deposition. As a result, the wall-plug efficiency of V-LEDs with an Al2O3 CBL at
      500 mA was improved by 5% as compared to those with a SiO2 CBL, and by 19% as
      compared to those without a CBL.

PMID- 22418679
TI  - Energy consumption in optical modulators for interconnects.
AB  - We analyze energy consumption in optical modulators operated in depletion and
      intended for low-power interconnect applications. We include dynamic dissipation
      from charging modulator capacitance and net energy consumption from absorption
      and photocurrent, both in reverse and small forward bias. We show that dynamic
      dissipation can be independent of static bias, though only with specific kinds of
      bias circuits. We derive simple expressions for the effects of photocurrent on
      energy consumption, valid in both reverse and small forward bias. Though
      electroabsorption modulators with large reverse bias have substantial energy
      penalties from photocurrent dissipation, we argue that modulator diodes with thin
      depletion regions and operating in small reverse and/or forward bias could have
      little or no such photocurrent energy penalty, even conceivably being more energy
      efficient than an ideal loss-less modulator.

PMID- 22418680
TI  - Improved light extraction efficiency in organic light emitting diodes with a
      perforated WO3 hole injection layer fabricated by use of colloidal lithography.
AB  - We present an organic light emitting diode with a perforated WO3 hole injection
      layer to improve the light extraction efficiency. The two-dimensionally
      perforated WO3 layer was fabricated by use of colloidal lithography. The light
      extraction efficiency was improved due to Bragg scattering of waveguide modes and
      surface plasmon polaritons, and the operating voltage was also decreased. As a
      result, the external quantum efficiency and the power efficiency were increased
      as compared with those of conventional organic light emitting diodes without WO3
      layer. The angular dependence of emission characteristics was investigated by
      measuring radiant intensity profiles for emission angles and azimuthal angles.

PMID- 22418681
TI  - Highly efficient CdS-quantum-dot-sensitized GaAs solar cells.
AB  - We demonstrate a hybrid design of traditional GaAs-based solar cell combined with
      colloidal CdS quantum dots. With anti-reflective feature at long wavelength and
      down-conversion at UV regime, the CdS quantum dot effectively enhance the overall
      power conversion efficiency by as high as 18.9% compared to traditional GaAs
      based device. A more detailed study showed an increase of surface
      photoconductivity due to UV presence, and the fill factor of the solar cell can
      be improved accordingly.

PMID- 22418682
TI  - Spectral optical properties of Cu2ZnSnS4 thin film between 0.73 and 6.5 eV.
AB  - A polycrystalline Cu2ZnSnS4 thin film was deposited on fused quartz by co
      evaporation. The selected thickness was ~100 nm to avoid artifacts in its optical
      properties caused by thicker as-grown films. The composition and phase of the
      film were checked with x-ray fluorescence, Raman shift spectroscopy, scanning
      transmission electron microscopy, and energy dispersive x-ray spectroscopy. An
      improved spectroscopic ellipsometry methodology with two-side measurement
      geometries was applied to extract the complex dielectric function epsilon =
      epsilon1 + iepsilon2 of the Cu2ZnSnS4 thin film between 0.73 and 6.5 eV. Five
      critical points were observed, at 1.32 (fundamental band gap), 2.92, 3.92, 4.96,
      and 5.62 eV, respectively. The epsilon spectra are in reasonable agreement with
      those from theoretical calculations.

PMID- 22418683
TI  - Nonradiative energy transfer between colloidal quantum dot-phosphors and
      nanopillar nitride LEDs.
AB  - We present in this communication our study of the nonradiative energy transfer
      between colloidal quantum dot (QD) phosphors and nitride nanopillar light
      emitting diodes (LEDs). An epitaxial p-i-n InGaN/GaN multiple quantum-well (QW)
      heterostructure was patterned and dry-etched to form dense arrays of nanopillars
      using a novel etch mask consisting of self-assembled In3Sn clusters. Colloidal QD
      phosphors have been deposited into the gaps between the nanopillars, leading to
      sidewall coupling between the QDs and InGaN QW emitters. In this approach, close
      QW-QD contact and a low-resistance design of the LED contact layer were achieved
      simultaneously. Strong non-radiative energy transfer was observed from the InGaN
      QW to the colloidal QD phosphors, which led to a 263% enhancement in effective
      internal quantum efficiency for the QDs incorporated in the nanopillar LEDs, as
      compared to those deposited over planar LED structures. Time-resolved
      photoluminescence was used to characterize the energy transfer process between
      the QW and QDs. The measured rate of non-radiative QD-QW energy-transfer agrees
      well with the value calculated from the quantum efficiency data for the QDs in
      the nanopillar LED.

PMID- 22418684
TI  - Bacteria-directed construction of hollow TiO2 micro/nanostructures with enhanced
      photocatalytic hydrogen evolution activity.
AB  - A general method has been developed for the synthesis of various hollow TiO2
      micro/nanostructures with bacteria as templates to further study the structural
      effect on photocatalytic hydrogen evolution properties. TiO2 hollow spheres and
      hollow tubes, served as prototypes, are obtained via a surface sol-gel process
      using cocci and bacillus as biotemplates, respectively. The formation mechanisms
      are based on absorption of metal-alkoxide molecules from solution onto functional
      cell wall surfaces and subsequent hydrolysis to give nanometer-thick oxide
      layers. The UV-Vis absorption spectrum shows that the porous TiO2 hollow spheres
      have enhanced light harvesting property compared with the corresponding solid
      counterpart. This could be attributed to their unique hollow porous
      micro/nanostructures with microsized hollow cavities and nanovoids which could
      bring about multiple scattering and rayleigh scattering of light, respectively.
      The hollow TiO2 structures exhibit superior photocatalytic hydrogen evolution
      activities under UV and visible light irradiation in the presence of sacrificial
      reagents. The hydrogen evolution rate of hollow structures is about 3.6 times
      higher than the solid counterpart and 1.5 times higher than P25-TiO2. This work
      demonstrates the structural effect on enhancing the photocatalytic hydrogen
      evolution performance which would pave a new pathway to tailor and improve
      catalytic properties over a broad range.

PMID- 22418685
TI  - Visible light-driven photocatalysis of doped SrTiO3 tubular structure.
AB  - SrTiO3 tubular structures co-doped with Cr and Ta were synthesized through a
      combination of solvothermal-hydrothermal processes. X-ray photoelectron
      spectroscopy (XPS) measurements of the oxidation state of Cr ions reveal that the
      formation of Cr6+ ions, which would serve as the non-radiative recombination
      centers for photogenerated electrons and holes, was suppressed without the
      process of high temperature hydrogen reduction. Compared to similar co-doped
      materials synthesized by solid-state reaction, (Cr, Ta) co-doped SrTiO3 tubular
      structures have significantly higher photocatalytic activity for hydrogen
      evolution as measured in an aqueous methanol solution under visible light
      irradiation.

PMID- 22418686
TI  - Photocatalytic alkoxylation of benzene with 3-cyano-1-methylquinolinium ion.
AB  - One-pot alkoxylation of benzene with alcohols occurs under photoirradiation of 3
      cyano-1-methylquinolinium ion in an oxygen-saturated acetonitrile solution
      containing benzene and alcohols. The photocatalytic reaction mechanism was
      clarified by nanosecond laser flash photolysis. The photocataytic alkoxylation of
      benzene is initiated by photoinduced electron transfer from benzene to the
      singlet excited state of 3-cyano-1-methylquinolinium ion, followed by the
      nucleophilic addition of alcohols to benzene radical cation. In the case of
      photoethoxylation, the optimal product and quantum yields of ethoxybenzene were
      20% and 10%, respectively.

PMID- 22418687
TI  - Investigating the solid state hosting abilities of homo- and hetero-valent [Co7]
      metallocalix[6]arenes.
AB  - A family of homo-valent [Co(II)(7)(OH)(6)(L(1))(6)](NO(3))(2) (1), [(MeOH)(2) is
      a subset of Co(II)(7)(OH)(6)(L(1))(6)](NO(3))(2) (2) (where L(1)H = 2-iminomethyl
      6-methoxyphenol) and hetero-valent [(NO(3))(2) is a subset of
      Co(III)Co(II)(6)(OH)(6)(L(2))(6)](NO(3)).3MeCN (4) (where L(2)H = 2-iminophenyl-6
      methoxyphenol) complexes possess metallic skeletons describing planar hexagonal
      discs. Their organic exteriors form double-bowl shaped topologies, and coupled
      with their 3-D connectivity, this results in the formation of molecular cavities
      in the solid state. These confined spaces are shown to behave as host units in
      the solid state for guests including solvent molecules and charge balancing
      counter anions. Magnetic susceptibility measurements on 2 and 4 reveal weak ferro
      and ferrimagnetism, respectively. The utilisation of other Co(II) salt
      precursors gives rise to entirely different species including the mononuclear and
      trinuclear complexes [Co(II)(L(2))(2)] (5) and
      [Co(III)(2)Na(I)(1)(L(3))(6)](BF(4)) (6) (where L(3)H = 2-iminomethyl-4-bromo-6
      methoxyphenol).

PMID- 22418688
TI  - Allocation of 14C assimilated in late spring to tissue and biochemical stem
      components of cork oak (Quercus suber L.) over the seasons.
AB  - Carbon distribution in the stem of 2-year-old cork oak plants was studied by
      (14)CO(2) pulse labeling in late spring in order to trace the allocation of
      photoassimilates to tissue and biochemical stem components of cork oak. The fate
      of (14)C photoassimilated carbon was followed during two periods: the first 72 h
      (short-term study) and the first 52 weeks (long-term study) after the (14)CO(2)
      photosynthetic assimilation. The results showed that (14)C allocation to stem
      tissues was dependent on the time passed since photoassimilation and on the
      season of the year. In the first 3 h all (14)C was found in the polar
      extractives. After 3 h, it started to be allocated to other stem fractions. In 1
      day, (14)C was allocated mostly to vascular cambium and, to a lesser extent, to
      primary phloem; no presence of (14)C was recorded for the periderm. However,
      translocation of (14)C to phellem was observed from 1 week after (14)CO(2) pulse
      labeling. The phellogen was not completely active in its entire circumference at
      labeling, unlike the vascular cambium; this was the tissue that accumulated most
      photoassimilated (14)C at the earliest sampling. The fraction of leaf-assimilated
      (14)C that was used by the stem peaked at 57% 1 week after (14)CO(2) plant
      exposure. The time lag between C photoassimilation and suberin accumulation was
      ~8 h, but the most active period for suberin accumulation was between 3 and 7
      days. Suberin, which represented only 1.77% of the stem weight, acted as a highly
      effective sink for the carbon photoassimilated in late spring since suberin
      specific radioactivity was much higher than for any other stem component as early
      as only 1 week after (14)C plant labeling. This trend was maintained throughout
      the whole experiment. The examination of microautoradiographs taken over 1 year
      provided a new method for quantifying xylem growth. Using this approach it was
      found that there was more secondary xylem growth in late spring than in other
      times of the year, because the calculated average cell division time was much
      shorter.

PMID- 22418689
TI  - Evaluation of the 'putative' role of intraoperative intact parathyroid hormone
      assay during parathyroidectomy for secondary hyperparathyroidism. A retrospective
      study on 35 consecutive patients: intraoperative iPTH assay during
      parathyroidectomy.
AB  - In the surgical treatment of secondary hyperparathyroidism (2HPT) of chronic
      kidney disease (CKD), a parathyroidectomy (PTx) of 4 glands can only be presumed
      as 'total', and indications for autoimplantation are complex. Intraoperative
      rapid parathyroid hormone assay could be useful to predict a radical resection.
      We evaluated iPTH levels 20 min and 24 h after a 4-gland PTx in 35 patients to
      determine the predictive value of intraoperative iPTH assay. We analysed
      retrospectively 35 patients affected by 2HPT of CKD, 13 undergoing total
      parathyroidectomy (TP) and 22 TP + autoimplantation (TPai), after removing 4
      glands in 33 cases and 5 glands in 2. Intact PTH assays were acquired after 40
      min before induction of anaesthesia, after removing both ipselateral glands, at
      20 min after surgery and on postoperative day 1. 20 min after 4-gland PTx, a
      decrease of iPTH levels >80 % of the preoperative value was observed in 27 of 35
      cases (77.1 %) and <80 % in 8 of 35 cases (22.8 %). In 6 of these 8 patients,
      iPTH levels were within the normal range 24 h after surgery. Although the
      intraoperative iPTH assays are of interest in the treatment of 2HPT, the
      predictive value of this method is not entirely satisfactory. In fact, a 4-gland
      PTx ensures euparathyroidism in most cases, even when intraoperative iPTH assays
      are not trustworthy; however, intraoperative iPTH assay, although not a perfect
      'tool', is a proved aid for the surgeon in making his decision.

PMID- 22418691
TI  - Surgery and tuberculosis.
AB  - PURPOSE OF REVIEW: Tuberculosis (TB) remains a global emergency and continues to
      kill 1.7 million people globally each year. In the UK, figures for TB are
      increasing especially in urban areas. There have been advances in imaging
      techniques as well as increasingly invasive medical interventions in both the
      diagnosis and treatment of this complex disease. Surgery continues to play an
      evolving and more challenging role in TB management as minimally invasive
      procedures can be increasingly used in diagnosis and treatment. Open surgical
      procedures continue to prove an important adjunct in the management of multidrug
      resistant TB (MDR-TB) and the complications of TB. RECENT FINDINGS: Since the
      peak of surgical treatment for TB in the 1950s, surgery is currently mainly
      reserved for 'difficult-to-diagnose' or indeed 'difficult-to-treat' cases of TB.
      Improved diagnostics, medical imaging and invasive medical interventions have all
      enabled alternatives to early surgical intervention. As improving minimally
      invasive surgical techniques provide diagnostic and treatment options, older
      methods of surgically managing complex TB have been revisited. To date most of
      the studies are retrospective and observatory but large studies and meta-analyses
      are showing the continued role surgery has to play in the treatment of TB.
      SUMMARY: This review will focus on new diagnostic imaging techniques and medical
      interventions which may become increasingly available in both developing
      countries and in the Western world. It will also highlight the continued role of
      minimally invasive video-assisted thoracoscopic surgery as well as open surgery
      in managing TB and MDR-TB.

PMID- 22418690
TI  - Cardiotrophin-1 in hypertensive heart disease.
AB  - Hypertensive heart disease, here defined by the presence of pathologic left
      ventricular hypertrophy in the absence of a cause other than arterial
      hypertension, is characterized by complex changes in myocardial structure
      including enhanced cardiomyocyte growth and non-cardiomyocyte alterations that
      induce the remodeling of the myocardium, and ultimately, deteriorate left
      ventricular function and facilitate the development of heart failure. It is now
      accepted that a number of pathological processes mediated by mechanical,
      neurohormonal, and cytokine routes acting on the cardiomyocyte and the non
      cardiomyocyte compartments are responsible for myocardial remodeling in the
      context of arterial hypertension. For instance, cardiotrophin-1 is a cytokine
      member of the interleukin-6 superfamily, produced by cardiomyocytes and non
      cardiomyocytes in situations of biomechanical stress that once secreted interacts
      with its receptor, the heterodimer formed by gp130 and gp90 (also known as
      leukemia inhibitory factor receptor beta), activating different signaling
      pathways leading to cardiomyocyte hypertrophy, as well as myocardial fibrosis.
      Beyond its potential mechanistic contribution to the development of hypertensive
      heart disease, cardiotrophin-1 offers the opportunity for a new translational
      approach to this condition. In fact, recent evidence suggests that cardiotrophin
      1 may serve as both a biomarker of left ventricular hypertrophy and dysfunction
      in hypertensive patients, and a potential target for therapies aimed to prevent
      and treat hypertensive heart disease beyond blood pressure control.

PMID- 22418692
TI  - Evidence of high genetic variation among linguistically diverse populations on a
      micro-geographic scale: a case study of the Italian Alps.
AB  - Although essential for the fine-scale reconstruction of genetic structure, only a
      few micro-geographic studies have been carried out in European populations. This
      study analyzes mitochondrial variation (651 bp of the hypervariable region plus
      17 single-nucleotide polymorphisms) in 393 samples from nine populations from
      Trentino (Eastern Italian Alps), a small area characterized by a complex
      geography and high linguistic diversity. A high level of genetic variation,
      comparable to geographically dispersed European groups, was observed. We found a
      difference in the intensity of peopling processes between two longitudinal areas,
      as populations from the west-central part of the region show stronger signatures
      of expansion, whereas those from the eastern area are closer to the expectations
      of a stationary demographic state. This may be explained by geomorphological
      factors and is also supported by archeological data. Finally, our results reveal
      a striking difference in the way in which the two linguistically isolated
      populations are genetically related to the neighboring groups. The Ladin speakers
      were found to be genetically close to the Italian-speaking populations and
      differentiated from the other Dolomitic Ladins, whereas the German-speaking
      Cimbri behave as an outlier, showing signatures of founder effects and low growth
      rate.

PMID- 22418693
TI  - High-yield Escherichia coli-based cell-free expression of human proteins.
AB  - Production of sufficient amounts of human proteins is a frequent bottleneck in
      structural biology. Here we describe an Escherichia coli-based cell-free system
      which yields mg-quantities of human proteins in N-terminal fusion constructs with
      the GB1 domain, which show significantly increased translation efficiency. A
      newly generated E. coli BL21 (DE3) RIPL-Star strain was used, which contains a
      variant RNase E with reduced activity and an excess of rare-codon tRNAs, and is
      devoid of lon and ompT protease activity. In the implementation of the expression
      system we used freshly in-house prepared cell extract. Batch-mode cell-free
      expression with this setup was up to twofold more economical than continuous
      exchange expression, with yields of 0.2-0.9 mg of purified protein per mL of
      reaction mixture. Native folding of the proteins thus obtained is documented with
      2D [(15)N,(1)H]-HSQC NMR.

PMID- 22418695
TI  - Hydrogen tunnelling influences the isomerisation of some small radicals of
      interstellar importance. A theoretical investigation.
AB  - Hydrogen atom isomerisations within five radical systems (i.e., CH(3)NH/CH(2)NH;
      CH(3)O/CH(2)OH; CH(2)SH/CH(3)S; CH(3)CO(2)/CH(2)CO(2)H; and
      HOCH(2)CH(2)O/HOCHCH(2)OH) have been studied via quantum-mechanical hydrogen
      tunnelling through reaction barriers. The reaction rates including hydrogen
      tunnelling effects have been calculated for these gas phase reactions at
      temperatures from 300 K to 0 K using Wenzel-Kramers-Brillouin (WKB) and Eckart
      methods. The Eckart method has been found to be unsatisfactory for the last two
      systems listed above, because it significantly underestimates the width of the
      reaction barriers for the interconversions. The calculations at all-electron
      CCSD(T)/CBS level of theory indicate that the barriers for all reactions (forward
      and reverse) are greater than 100 kJ mol(-1), meaning that the chemical
      reactivity of the reactants is limited in the absence of hydrogen tunnelling.
      Hydrogen tunnelling, in some cases, enhance rates of reaction by more than 100
      orders of magnitude at low temperature, and around 2 orders of magnitude at room
      temperature, compared to results obtained from canonical variational transition
      state theory. Tunnelling corrected reaction rates suggest that some of these
      isomerisation reactions may occur in interstellar media.

PMID- 22418694
TI  - Influence of nebulizer type with different pediatric aerosol masks on drug
      deposition in a model of a spontaneously breathing small child.
AB  - BACKGROUND: The performance of nebulizers varies with the design type as well as
      the breathing patterns of various age groups. The present study quantified
      aerosol delivery using spontaneously breathing parameters of a small child (2-4
      years) by a lung simulator to determine  the influence of nebulizer type,
      actuation mechanisms, and pediatric aerosol masks. METHODS: Three types of
      nebulizer (constant-output, breath-enhanced, and breath-actuated nebulizer) and 3
      masks (standard pediatric mask, the Fish mask, and a valved mask) were chosen for
      the testing. The actuation  mechanism of the breath-actuated nebulizer was tested
      by manual synchronization with inspiration, breath actuation, and continuous
      nebulization. The nebulizer performance was determined by determining mass median
      aerodynamic diameter and analyzing drug deposition distal to the trachea (inhaled
      mass), on the face, on the mask, residual drug in the nebulizer, and the time of
      nebulization. The quantity of salbutamol deposited was determined by
      spectrophotometry (276 nm). RESULTS: Mass median aerodynamic diameter was similar
      across nebulizers. Breath-actuated nebulization generated  a lower inhaled dose
      and higher nebulization time than continuous nebulization (P = .001). Breath
      synchronized aerosol generation, whether breath-actuated or manually actuated,
      yielded 10-20 times lower inhaled mass than continuous nebulization (0.1-0.6% vs
      5-11%,  respectively). The AeroEclipse, operated continuously, delivered greater
      inhaled dose than the LC Plus (P = .025). Higher inhaled dose was achieved with
      the Fish mask than standard or valved mask, with all nebulizers tested (P =
      .001). CONCLUSIONS: In this model using ventilatory  parameters associated with a
      2-4-year-old child, breath-actuated nebulization was not as effective as
      continuous nebulization. Aerosol mask design can impact inhaled drug dose across
      the range of nebulizers tested.

PMID- 22418696
TI  - [Surgical research in Germany. Organization, quality and international
      competitiveness].
AB  - Surgical research in Germany is performed within surgical clinics by individual
      working groups or in surgical research divisions. Additionally, a few independent
      institutes and departments of surgical research have been established at medical
      faculties. The number of these institutions, however, is too small. To increase
      productivity in surgical research, structural changes are necessary, including
      additional establishment of further institutes and professorships. The quality of
      clinical research in surgery in Germany is critically discussed. International
      comparison shows that Germany has a low ranking with respect to the number of
      clinical studies published in leading surgical journals. However, there has been
      some improvement in the quality of clinical studies performed in surgical
      departments during the last 15 years. The establishment of the study center of
      the German Society of Surgery shows that excellent clinical studies with adequate
      numbers of patients can also be performed in Germany and can be published in
      leading journals. Accordingly, there is need to distribute the structures and the
      competence necessary to perform clinical studies in a standardized manner to all
      surgical departments involved in clinical research. The experimental surgical
      research in Germany is not adequately visible, although over the last 10 years
      the most relevant publications from institutions for surgical research have been
      placed in journals with a mean impact factor of 8. This may be due to the fact
      that 85% of these top publications are published in non-surgical journals. The
      aim for the future must therefore be to increase the impact factor and, thus, the
      attractiveness of surgical journals. This may be achieved by publishing the
      highest quality results from experimental surgical research not in non-surgical
      but in surgical journals.

PMID- 22418697
TI  - [Robotic versus open pancreatoduodenectomy. To early for a valid comparative
      study].

PMID- 22418698
TI  - Venous thromboembolism: a collaborative quality improvement model for
      practitioners, hospitals, and insurers.
AB  - Venous thromboembolism (VTE) carries significant morbidity and mortality and
      affects a large portion of hospitalized patients. VTE prophylaxis is rated by the
      Agency for Healthcare Research and Quality as the most effective of 79 patient
      safety practices it assessed in 2001. Since 1997, Blue Cross Blue Shield of
      Michigan/Blue Care Network (BCBSM/BCN) have partnered with Michigan hospitals and
      providers in statewide registry-based collaborative quality improvement
      initiatives (CQI) aimed at improving the safety and quality of surgical and
      medical care; many of these collaborative have a particular focus on VTE
      prevention. The CQIs are uniquely structured to catalyze hospitals and
      practitioners to become self-optimizing. In this review, we describe the model
      BCBSM/BCN and participating Michigan hospitals have developed to improve the
      prevention and diagnosis of VTE for patients in the state of Michigan.

PMID- 22418699
TI  - A randomized trial of combination anastrozole plus gefitinib and of combination
      fulvestrant plus gefitinib in the treatment of postmenopausal women with hormone
      receptor positive metastatic breast cancer.
AB  - EGFR signalling pathways appear involved in endocrine therapy resistance in
      breast cancer. This trial estimates the antitumor efficacy and toxicity of the
      EGFR tyrosine kinase inhibitor gefitinib in combination with anastrozole or
      fulvestrant in postmenopausal hormone receptor positive breast cancer. Subjects
      with estrogen receptor and/or PgR positive, metastatic breast cancer were
      randomized into this phase II study of gefitinib (initial dose was 500 mg orally
      daily, due to high rate of diarrhea, starting dose was reduced to 250 mg orally
      daily) with either anastrozole 1 mg daily or fulvestrant 250 mg every 4 weeks.
      The primary endpoint was clinical benefit (complete responses plus partial
      responses plus stable disease for 6 months or longer). 141 eligible subjects were
      enrolled, 72 in the anastrozole plus gefitinib arm, and 69 in the fulvestrant
      plus gefitinib arm. Anastrozole plus gefitinib had a clinical benefit rate of 44%
      [95% confidence interval (CI) 33-57%] and fulvestrant plus gefitinib 41% (95% CI
      29-53%). Median progression-free survival was 5.3 months (95% CI 3.1-10.4) versus
      5.2 months (95% CI 2.9-8.2) for anastrozole plus gefitinib versus fulvestrant
      plus gefitinib, respectively. Median survival was 30.3 months (95% CI 21.2-38.9+)
      versus 23.9 months (95% CI 15.4-33.5) for anastrozole plus gefitinib versus
      fulvestrant plus gefitinib, respectively. In general, the toxicity is greater
      than expected for single agent endocrine therapy alone. Anastrozole plus
      gefitinib and fulvestrant plus gefitinib have similar clinical benefit rates in
      the treatment of estrogen and/or PgR positive metastatic breast cancer, and the
      rates of response are not clearly superior to gefitinib or endocrine therapy
      alone. Further studies of EGFR inhibition plus endocrine therapy do not appear
      warranted, but if performed should include attempts to identify biomarkers
      predictive of antitumor activity.

PMID- 22418700
TI  - A phase II study of afatinib (BIBW 2992), an irreversible ErbB family blocker, in
      patients with HER2-positive metastatic breast cancer progressing after
      trastuzumab.
AB  - Afatinib is an oral, ErbB family blocker, which covalently binds and irreversibly
      blocks all kinase-competent ErbB family members. This phase II, open-label,
      single-arm study explored afatinib activity in human epidermal growth factor
      receptor 2 (HER2)-positive breast cancer patients progressing after trastuzumab
      treatment. Patients had stage IIIB/IV HER2-positive metastatic breast cancer,
      with progression following trastuzumab or trastuzumab intolerance and an Eastern
      Cooperative Oncology Group (ECOG) performance status of 0-2. Patients received 50
      mg afatinib once-daily until disease progression. Primary endpoint was objective
      response rate (Response Evaluation Criteria in Solid Tumors 1.0), with tumor
      assessments every 8 weeks. Forty-one patients were treated. Patients had received
      a median of three prior chemotherapy lines (range, 0-15) and 68.3% had received
      trastuzumab for >1 year. Four patients (10% of 41 treated; 11% of evaluable
      patients) had partial response. Fifteen patients (37% of 41) had stable disease
      as best response and 19 (46% of 41) achieved clinical benefit. Median progression
      free survival was 15.1 weeks (95% confidence interval [CI]: 8.1-16.7); median
      overall survival was 61.0 weeks (95% CI: 56.7-not evaluable). Most frequent
      common terminology criteria for adverse events grade 3 treatment-related adverse
      events were diarrhea (24.4%) and rash (9.8%). Afatinib monotherapy was associated
      with promising clinical activity in extensively pretreated HER2-positive breast
      cancer patients who had progressed following trastuzumab treatment.

PMID- 22418701
TI  - Polymorphisms of CYP19A1 and response to aromatase inhibitors in metastatic
      breast cancer patients.
AB  - Single nucleotide polymorphisms (SNPs) in the gene encoding aromatase (CYP19A1)
      have been associated with differential benefit from letrozole treatment in
      metastatic breast cancer (mBC) patients, but validation is lacking. The aim was
      to investigate whether polymorphic variation of CYP19A1 and enzymes involved in
      estrogen and aromatase inhibitors (AIs) metabolism are associated with efficacy
      of AIs. 308 Women with estrogen-receptor-positive metastatic mBC treated with a
      third-generation AI were identified retrospectively. DNA was extracted from
      archival formalin-fixed paraffin embedded tumors and genotyped for 71 variants in
      16 candidate genes, including CYP19A1. Time to treatment failure (TTF) was
      significantly improved in patients carrying the minor (T) allele of rs4775936
      when compared to patients with the reference allele [HR = 0.79 per T allele (0.66
      0.95); P = 0.012]. Patients with >7 TTTA repeats on either allele of CYP19A1
      intron 4 had a lower risk of failure than those with a smaller repeat size [HR =
      0.84 per >7 TTTA repeats (0.7-0.99); P = 0.04]. However, importantly in
      multivariate analysis, adjusting for the number of disease sites; disease-free
      interval from diagnosis to first recurrence, grade at diagnosis and first
      recurrence type neither variant maintained independent predictive significance.
      None of the 56 SNPs analyzed as an exploratory set showed significant association
      with TTF. Variants in CYP19A1 or other selected genes associated with AI
      metabolism were not independently associated with improved AI efficacy and
      emphasize the importance in pharmacogenetic studies of considering genetic
      biomarkers in the context of relevant prognostic factors.

PMID- 22418702
TI  - Mesothelin, a novel immunotherapy target for triple negative breast cancer.
AB  - Mesothelin is a cell-surface glycoprotein present on mesothelial cells and
      elicits T cell responses in a variety of cancers including pancreatic, biliary
      and ovarian cancer. Breast cancer is not known to express mesothelin. We
      postulated that mesothelin may be a unique tumor-associated antigen in triple
      negative breast cancer (TNBC), a less common breast cancer subtype which may have
      been under-represented in prior studies that characterized mesothelin expression.
      Therefore, we screened 99 primary breast cancer samples by immunohistochemistry
      analysis using formalin-fixed paraffin-embedded archival tumor tissues and
      confirmed that mesothelin was overexpressed in the majority of TNBC (67 %) but
      only rarely in <5 % ER(+) or Her2-neu(+) breast cancer, respectively. To
      determine whether mesothelin may be exploited as a novel immunotherapy target in
      breast cancer, an in vitro cell killing assay was performed to compare the
      ability of genetically modified T cells expressing a chimeric antibody receptor
      (CAR) specific for mesothelin (mesoCAR T cells) or non-transduced T cells to kill
      mesothelin-expressing primary breast cancer cells. A significantly higher anti
      tumor cytotoxicity by mesoCAR T cells was observed (31.7 vs. 8.7 %, p < 0.001).
      Our results suggest that mesothelin has promise as a novel immunotherapy target
      for TNBC for which effective targeted therapy is lacking to date.

PMID- 22418703
TI  - Accuracy of quantitative ultrasound elastography for differentiation of malignant
      and benign breast abnormalities: a meta-analysis.
AB  - The purpose of this study was to systematically review recent literature on
      diagnostic performance of strain ratio and length ratio, two different strain
      measurements in ultrasound elastography, for differentiating benign and malignant
      breast masses. A literature search of PubMed and other medical and general
      purpose databases from inception through January 2012 was conducted. Published
      studies that evaluated the diagnostic performance of ultrasound elastography
      alone reporting either strain ratio or length ratio for characterization of focal
      breast lesions and using cytology (fine needle aspiration) or histology (core
      biopsy) as a reference standard were included. Summary diagnostic performance
      measures were assessed using bivariate generalized linear mixed modeling. Nine
      studies reported strain ratio for 2,087 breast masses (667 cancers, 1,420 benign
      lesions). Summary sensitivity and specificity were 88 % (95 % Credible Interval
      (CrI), 84-91 %), and 83 % (95 % CrI, 78-88 %), respectively. The positive and
      negative likelihood ratios (LR) were 5.57 (95 % CrI, 3.85-8.01) and 0.14 (95 %
      CrI, 0.09-0.20), respectively. The inconsistency index for heterogeneity was 6 %
      (95 % CrI, 1-22 %) for sensitivity and 8 % (95 % CrI, 3-24 %) for specificity.
      Analysis of three studies reporting length ratio for 450 breast masses
      demonstrated sensitivity and specificity of 98 % (95 % CrI, 93-99 %) and 72 % (95
      % CrI, 31-96 %), respectively. Strain ratio and length ratio have good diagnostic
      performance for distinguishing benign from malignant breast masses. Although,
      this performance may not be incrementally superior to that of breast imaging
      reporting and data system (BIRADS) in B-mode ultrasound, the application of USE
      using strain ratio or length ratio in combination with USB may have the potential
      to benefit the patients, and this requires further comparative effectiveness and
      cost-effectiveness analyses.

PMID- 22418704
TI  - Thermal acclimation is not necessary to maintain a wide thermal breadth of
      aerobic scope in the common killifish (Fundulus heteroclitus).
AB  - Loss of aerobic scope at high and low temperatures is a physiological mechanism
      proposed to limit the thermal performance and tolerance of organisms, a theory
      known as oxygen- and capacity-limited thermal tolerance (OCLTT). Eurythermal
      organisms maintain aerobic scope over wide ranges of temperatures, but it is
      unknown whether acclimation is necessary to maintain this breadth. The objective
      of this study was to examine changes in aerobic scope in Fundulus heteroclitus, a
      eurythermal fish, after acclimation and acute exposure to temperatures from 5
      degrees  to 33 degrees C. The range of temperatures over which aerobic scope was
      nonzero was similar in acclimated and acutely exposed fish, suggesting that
      acclimation has modest effects on the thermal breadth of aerobic scope. However,
      in acclimated fish, there was a clear optimum temperature range for aerobic scope
      between 25 degrees  and 30 degrees C, whereas aerobic scope was relatively
      constant across the entire temperature range with acute temperature exposure.
      Therefore, the primary effect of acclimation was to increase aerobic scope
      between 25 degrees  and 30 degrees C, which paradoxically resulted in a narrower
      temperature range of optimal performance in acclimated fish compared to acutely
      exposed fish. There was only weak evidence for correlations between the thermal
      optimum of aerobic scope and the thermal optimum of measures of performance
      (specific growth rate and gonadosomatic index), and indicators of anaerobic
      metabolism (lactate accumulation and lactate dehydrogenase activity) only
      increased at high temperatures. Together these data fit many, but not all, of the
      predictions made by OCLTT.

PMID- 22418705
TI  - Muscle energy stores and stroke rates of emperor penguins: implications for
      muscle metabolism and dive performance.
AB  - In diving birds and mammals, bradycardia and peripheral vasoconstriction
      potentially isolate muscle from the circulation. During complete ischemia, ATP
      production is dependent on the size of the myoglobin oxygen (O(2)) store and the
      concentrations of phosphocreatine (PCr) and glycogen (Gly). Therefore, we
      measured PCr and Gly concentrations in the primary underwater locomotory muscle
      of emperor penguin and modeled the depletion of muscle O(2) and those energy
      stores under conditions of complete ischemia and a previously determined muscle
      metabolic rate. We also analyzed stroke rate to assess muscle workload variation
      during dives and evaluate potential limitations on the model. Measured PCr and
      Gly concentrations, 20.8 and 54.6 mmol kg(-1), respectively, were similar to
      published values for nondiving animals. The model demonstrated that PCr and Gly
      provide a large anaerobic energy store, even for dives longer than 20 min. Stroke
      rate varied throughout the dive profile, indicating muscle workload was not
      constant during dives as was assumed in the model. The stroke rate during the
      first 30 s of dives increased with increased dive depth. In extremely long dives,
      lower overall stroke rates were observed. Although O(2) consumption and energy
      store depletion may vary during dives, the model demonstrated that PCr and Gly,
      even at concentrations typical of terrestrial birds and mammals, are a
      significant anaerobic energy store and can play an important role in the emperor
      penguin's ability to perform long dives.

PMID- 22418706
TI  - Biological and environmental drivers of energy allocation in a dependent mammal,
      the Antarctic fur seal pup.
AB  - Little is known about how variation in the pattern and magnitude of parental
      effort influences allocation decisions in offspring. We determined the energy
      budget of Antarctic fur seal pups and examined the relative importance of timing
      of provisioning, pup traits (mass, condition, sex), and weather (wind chill and
      solar radiation) on allocation of energy obtained in milk by measuring milk
      energy intake, field metabolic rate (FMR), and growth rate in 48 Antarctic fur
      seal pups over three developmental stages (perinatal, premolt, and molt). The
      relative amount of milk energy used for growth was 59.1% +/- 8.1% during the
      perinatal period but decreased to 23.4% +/- 15.5% and 26.0% +/- 13.9% during the
      premolt and molt. This decrease was associated with a greater amount of time
      spent fasting, along with an increase in pup activity while the mother was at sea
      foraging. Average daily milk intake, pup mass, and condition were all important
      in determining how much energy was available for growth, but the amount of energy
      obtained as milk was the single most important factor determining pup growth.
      While mean mass-specific FMR did not change with developmental stage (range =
      1.74-1.77 mL O(2)/g/h), the factors that accounted for variation in FMR did.
      Weather (wind chill and solar radiation) and pup traits (mass and condition)
      influenced mass-specific FMR, but these impacts varied across development. This
      study provides information about the factors influencing how offspring allocate
      energy toward growth and maintenance and improves our predictions about how a
      changing environment may affect energy allocation in pups.

PMID- 22418708
TI  - Ontogenetic scaling of metabolism, growth, and assimilation: testing metabolic
      scaling theory with Manduca sexta larvae.
AB  - Metabolism, growth, and the assimilation of energy and materials are essential
      processes that are intricately related and depend heavily on animal size.
      However, models that relate the ontogenetic scaling of energy assimilation and
      metabolism to growth rely on assumptions that have yet to be rigorously tested.
      Based on detailed daily measurements of metabolism, growth, and assimilation in
      tobacco hornworms, Manduca sexta, we provide a first experimental test of the
      core assumptions of a metabolic scaling model of ontogenetic growth. Metabolic
      scaling parameters changed over development, in violation of the model
      assumptions. At the same time, the scaling of growth rate matches that of
      metabolic rate, with similar scaling exponents both across and within
      developmental instars. Rates of assimilation were much higher than expected
      during the first two instars and did not match the patterns of scaling of growth
      and metabolism, which suggests high costs of biosynthesis early in development.
      The rapid increase in size and discrete instars observed in larval insect
      development provide an ideal system for understanding how patterns of growth and
      metabolism emerge from fundamental cellular processes and the exchange of
      materials and energy between an organism and its environment.

PMID- 22418707
TI  - Seasonal variation in the regulation of redox state and some biotransformation
      enzyme activities in the barn swallow (Hirundo rustica L.).
AB  - Little is known of the normal seasonal variation in redox state and
      biotransformation activities in birds. In long-distance migratory birds, in
      particular, seasonal changes could be expected to occur because of the demands of
      migration and reproduction. In this study, we measured several redox parameters
      in the barn swallow (Hirundo rustica L.) during the annual cycle. We captured the
      wintering barn swallows before spring migration in South Africa, and we captured
      the barn swallows that arrived in spring, bred in summer, and migrated in autumn
      in Finland. The redox status and biotransformation activities of barn swallows
      varied seasonally. Wintering birds in South Africa had high biotransformation
      activities and appeared to experience oxidative stress, whereas in spring and
      summer, they showed relatively low redox (superoxide dismutase [SOD], catalase
      [CAT], and glutathione reductase [GR]) and biotransformation enzyme activities.
      Autumn birds had very low biotransformation enzyme activities and low indication
      of oxidative stress but high activity of some redox enzymes (GR and glucose 6
      phosphate dehydrogenase [G6PDH]). High activities of some redox enzymes (SOD, GR,
      and G6PDH) seem to be related to migration, whereas low activities of some redox
      enzymes (SOD, CAT, and GR) may be associated with breeding. Barn swallows in
      South Africa may experience pollution-related oxidative stress, which may hamper
      interpretation of normal seasonal variation in redox parameters.

PMID- 22418709
TI  - Discontinuous gas exchange, water loss, and metabolism in Protaetia cretica
      (Cetoniinae, Scarabaeidae).
AB  - Insects are at high risk of desiccation because of their small size, high surface
      area-to-volume ratio, and air-filled tracheal system that ramifies throughout
      their bodies to transport O(2) and CO(2) to and from respiring cells. Although
      the tracheal system offers a high-conductance pathway for the movement of
      respiratory gases, it has the unintended consequence of allowing respiratory
      transpiration to the atmosphere. When resting, many species exchange respiratory
      gases discontinuously, and an early hypothesis for the origin of these
      discontinuous gas exchange cycles (DGCs) is that they serve to reduce respiratory
      water loss. In this study, we test this "hygric" hypothesis by comparing rates of
      CO(2) exchange and water loss among flower beetles Protaetia cretica (Cetoniinae,
      Scarabaeidae) breathing either continuously or discontinuously. We show that,
      consistent with the expectations of the hygric hypothesis, rates of total water
      loss are higher during continuous gas exchange than during discontinuous gas
      exchange and that the ratio of respiratory water loss to CO(2) exchange is lower
      during discontinuous gas exchange. This conclusion is in agreement with other
      studies of beetles and cockroaches that also support the hygric hypothesis.
      However, this result does not exclude other adaptive hypotheses supported by work
      on ants and moth pupae. This ambiguity may arise because there are multiple
      independent evolutionary origins of DGCs and no single adaptive function
      underlying their genesis. Alternatively, the observed reduction in water loss
      during DGCs may be a side effect of a nonadaptive gas exchange pattern that is
      elicited during periods of inactivity.

PMID- 22418710
TI  - Noninvasive monitoring of fecal cortisol metabolites in the eastern chipmunk
      (Tamias striatus): validation and comparison of two enzyme immunoassays.
AB  - Monitoring fecal glucocorticoid metabolites in wild animals, using enzyme
      immunoassays, enables the study of endocrinological patterns relevant to ecology
      and evolution. While some researchers use antibodies against the parent hormone
      (which is typically absent from fecal samples), others advocate the use of
      antibodies designed to detect glucocorticoid metabolites. We validated two assays
      to monitor fecal cortisol metabolites in the eastern chipmunk (Tamias striatus).
      We compared an antibody produced against cortisol and one produced against 5alpha
      pregnane-3beta, 11beta, 21-triol-20-one using a radiometabolism study and an
      injection with adrenocorticotropic hormone (ACTH). Most cortisol metabolites were
      excreted in the urine (~83%). Peak excretion in the feces occurred 8 h after
      injection. Both assays detected an increase in fecal cortisol metabolite levels
      after injection of ACTH. Males, but not females, exhibited a circadian variation
      in metabolite levels. The sexes did not exhibit any difference over the time
      course and route of excretion or the relative increase in fecal cortisol
      metabolite levels after ACTH injection. The cortisol assay displayed higher
      reactivity to ACTH injection relative to baseline than did the metabolite assay.
      While both antibodies gave comparable results, the cortisol antibody was more
      sensitive to changes in plasma cortisol levels in eastern chipmunks.

PMID- 22418711
TI  - Validation of noninvasive monitoring of adrenocortical endocrine activity in
      ground-feeding aardwolves (Proteles cristata): exemplifying the influence of
      consumption of inorganic material for fecal steroid analysis.
AB  - Biologically inert material in feces may confound interpretations of noninvasive
      fecal endocrine data, because it may induce variance related to differences in
      foraging behavior rather than to differences in endocrine activity. We evaluated
      two different enzyme immunoassays (EIAs) for the noninvasive evaluation of
      adrenocortical activity in ground-feeding aardwolves (Proteles cristata) and
      tested the influence of soil content in aardwolf feces on the interpretation of
      fecal glucocorticoid metabolite data. Using adrenocorticotropic hormone (ACTH)
      challenges for validation, we successfully identified a cortisol EIA suitable for
      assessing adrenocortical activity in aardwolves. An alternatively tested 11
      oxoetiocholanolone EIA failed to detect a biologically relevant signal after ACTH
      administration. Although the proportion of inorganic content in aardwolf feces
      did not alter qualitative conclusions from the endocrine data, the data related
      to mass of organic content had a larger amount of variance attributed to relevant
      biological contrasts and a lower amount of variance attributed to individual
      variation, compared with data related to total dry mass of extracted material.
      Compared with data expressed as dry mass of extracted material, data expressed as
      mass of organic content may provide a more refined and statistically powerful
      measure of endocrine activity in species that ingest large amounts of
      indigestible material.

PMID- 22418712
TI  - A comparison of pharmacokinetic methods for in vivo studies of nonmediated
      glucose absorption.
AB  - Two pharmacokinetic methods are used primarily to assess systematic
      bioavailability of orally dosed water-soluble compounds in vivo, but there have
      been no direct comparisons of the estimates obtained. The "area under the curve"
      (AUC) method employs a single oral dose of probe compound(s) followed by multiple
      blood sampling to obtain plasma concentration time curves. Separate injection of
      probe(s) followed by multiple blood sampling is used to calculate fractional
      elimination rate (K(el)) and distribution pool space (S). The "steady state
      feeding" method relies on ad lib. feeding of a marked diet, with a single blood
      sample taken to measure steady state feeding concentration of probe(s); K(el) is
      estimated from the decline in probe concentration in excreta after injection,
      with a single blood sample taken to estimate S. We compared these methods
      directly in the Australian red wattlebird (Anthochaera carnunculata), measuring
      absorption of (3)H-L-glucose. The K(el) values estimated using the steady state
      feeding protocol were significantly higher, and estimates of S and
      bioavailability consequently lower, compared with the AUC protocol. The AUC
      method relies on fewer assumptions and allows simultaneous comparisons of
      absorption by mediated and nonmediated (i.e., paracellular) mechanisms but cannot
      be easily applied to freely feeding animals. The steady state feeding method
      allows work with smaller species and exploration of the effects of feeding on
      nutrient uptake but requires careful attention to the validity of assumptions
      that increase error in the calculations.

PMID- 22418713
TI  - The miscibility and depth profile of PCBM in P3HT: thermodynamic information to
      improve organic photovoltaics.
AB  - Recent work has shown that poly(3-hexylthiophene) (P3HT) and the surface
      functionalized fullerene 1-(3-methyloxycarbonyl)propyl(1-phenyl[6,6])C(61) (PCBM)
      are much more miscible than originally thought, and the evidence of this
      miscibility requires a return to understanding the optimal morphology and
      structure of organic photovoltaic active layers. This manuscript describes the
      results of experiments that were designed to provide quantitative thermodynamic
      information on the miscibility, interdiffusion, and depth profile of P3HT : PCBM
      thin films that are formed by thermally annealing initial bilayers. It is found
      that the resultant thin films consist of a 'bulk' layer that is not influenced by
      the air or substrate surface. The composition of PCBM in this 'bulk' layer
      increases with increased PCBM loading in the original bilayer until the 'bulk'
      layer contains 22 vol% PCBM. The introduction of additional PCBM into the sample
      does not increase the amount of PCBM dispersed in this 'bulk' layer. This
      observation is interpreted to indicate that the miscibility limit of PCBM in P3HT
      is 22 vol%, while the precise characterization of the depth profiles in these
      films shows that the PCBM selectively segregates to the silicon and near air
      surface. The selective segregation of the PCBM near the air surface is ascribed
      to an entropic driving force.

PMID- 22418714
TI  - The survival curve:  factors impacting the outcome of free flap take-backs.
AB  - BACKGROUND: When vascular compromise is detected, a free flap is immediately
      taken back to the operating room for attempted salvage. Which factors predict the
      success or failure of a take-back is currently unknown. METHODS: A review of free
      flaps performed at a single institution over the last 10 years was performed. A
      total of 4965 flaps were identified, and an analysis of factors predicting
      salvage or failure of first, second, and third take-backs for microvascular
      complications was performed. RESULTS: Of 4965 flaps, 517 (10.3 percent) required
      return to the operating room, 157 (3.34 percent) for vascular complications.
      There were 66 (1.41 percent) total flap failures. Of 157 take-backs, 102 required
      return once, 44 twice, and 11 three times, with salvage rates of 72, 34, and 27
      percent, respectively (p < 0.01). Overall salvage rate was 58 percent. The
      probability of a flap going back for a second time was 35 percent. Risks for flap
      failure included thrombotic (35.1 percent) versus mechanical (8 percent) etiology
      (p = 0.01) and arterial (37.5 percent) or mixed (61.5 percent) versus venous only
      (25 percent) etiology (p = 0.06). Failure was more likely the greater number of
      days postoperatively the take-back occurred (p = 0.02). CONCLUSIONS: The number
      of returns to the operating room is inversely proportional to flap salvage.
      Mechanical and venous etiologies tend to result in salvage and arterial and
      thrombotic etiologies in failure. Earlier take-backs are more likely to be
      successful. Knowledge of these predictors of salvage should guide clinical
      decision making and informed consent. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk,
      II.

PMID- 22418715
TI  - Supermicrosurgical reconstruction of large defects on ischemic extremities using
      supercharging techniques on latissimus dorsi perforator flaps.
AB  - BACKGROUND: In patients with underlying vasculopathies, the unavailability of
      main vessels for conventional microsurgery may preclude limb salvage. However,
      with the evolution of supermicrosurgical techniques, anastomosis at the
      perforator level that is almost always spared by the underlying disease has
      become possible. To overcome insufficient flow in large flap issues following the
      procedure, a supercharging technique was used in reconstructions using a
      latissimus dorsi perforator free flap. METHODS: From January of 2008 to June of
      2010, a total of 21 patients underwent reconstructive procedures for large
      defects of the lower extremities using supermicrosurgery with arterial and/or
      venous supercharging techniques, including a latissimus dorsi perforator, an
      intercostal perforator, and the lateral thoracic vein. RESULTS: All flaps
      survived completely without arterial or venous problems. There were three minor
      complications of infection, venous congestion, and donor-site hematoma. Except
      for a hematoma evacuation procedure, complications were managed conservatively.
      CONCLUSIONS: : The latissimus dorsi perforator flap can be harvested with
      numerous latissimus dorsi perforators, intercostal perforators, and the lateral
      thoracic vein to perform the supercharging technique on reconstruction of large
      foot defects in patients with severe vasculopathy. This technique can be applied
      in various difficult situations, including traumatic injury of the main limb
      vessels, and can increase survival rates for limb salvage, particularly in
      ischemic limb reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      IV.

PMID- 22418716
TI  - Squamosal suture synostosis:  a cause of atypical skull asymmetry.
AB  - BACKGROUND: The squamosal suture is markedly different from the major calvarial
      sutures of the human skull. The unique properties of the suture are a result of
      the complex developmental biology of the temporal bone and biomechanical force
      exerted by surrounding structures. The dysmorphic effects of premature fusion of
      the suture, and possible treatment strategies in cases of synostosis, have
      received only brief description in the literature. METHODS: A retrospective case
      series was performed. The study included patients evaluated by one of the senior
      authors (S.P.B., R.R.R., and D.J.S.) between 1993 and 2009. All pertinent patient
      data including inpatient and outpatient charts, photographic records, and
      radiographic scans were reviewed. Any management performed under the direction of
      a craniofacial surgeon was documented--including orthotic helmet therapy and
      operative management. RESULTS: The study included 14 patients. Synostosis of the
      squamosal suture was noted to occur either in an isolated fashion or in the
      setting of other craniofacial malformations. Patients with isolated squamosal
      synostosis often suffered from a deformity that was mild in severity and tended
      to improve with time. However, when occurring in the setting of other forms of
      craniosynostosis, the deformity was often progressive, and transcranial surgery
      was frequently required. CONCLUSIONS: Synostosis of the squamosal suture can
      result in, or contribute to, significant craniofacial dysmorphism. The optimal
      form of therapy for this disorder is evolving.

PMID- 22418717
TI  - Climbing the ladder from novice to expert plastic surgeon.
AB  - This article reviews the nature of novice and expert thinking and shows how
      pattern recognition is a key distinction between the two. The article also
      discusses the ladder that learners climb as they move from medical student to
      senior staff surgeon and suggests ways of viewing surgical trainees as they
      progress through the process so that learning activities can be adopted that best
      fit them.

PMID- 22418718
TI  - Tip rhinoplasty in broad noses in a Turkish population: Eurasian noses.
AB  - BACKGROUND: Historically, one of the most persistent challenges to the
      rhinoplasty surgeon has been the thick, heavy, and poorly defined nasal tip. In
      the Mediterranean, Anatolian, and Middle Eastern regions, rhinoplasty is the most
      frequently performed aesthetic procedure. In these regions, the ethnic
      characteristic of the nasal tip is mostly broad with thick skin, a poorly defined
      nasal tip, and weak lower lateral cartilages, which makes shaping the tip
      challenging. In this population, conventional rhinoplasty techniques may result
      in dissatisfied patients and surgeons. METHODS: The author presents his
      experience over the past 20 years with 3800 rhinoplasty patients with broad noses
      treated using his personal approach. RESULTS: Using the Turkish delight type of
      cartilage graft (diced cartilage wrapped in Surgicel) for the tip region and the
      columellar strut improved the author's results considerably, giving the tip the
      desired form and eliminating the complications of late show seen in other types
      of tip grafts. In patients with very short columellae, insertion of a secondary
      strut was necessary after 1 year. CONCLUSIONS: : This technique is safe,
      reliable, effective, simple, and easily applicable by plastic surgeons at all
      experience levels. Early and late results are very satisfactory, and there is no
      late show as is sometimes seen with other types of cartilage grafts such as
      crushed, oval, or rectangular grafts. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 22418720
TI  - The use of adipose tissue-derived stem cells within a dermal substitute improves
      skin regeneration by increasing neoangiogenesis and collagen synthesis.
AB  - BACKGROUND: Surgical treatment of injuries with loss of skin tissue has improved
      significantly with the advent of regenerative medicine and tissue bioengineering,
      and the use of stem cells and dermal substitutes. The success of tissue
      regeneration depends on optimal local vascularization and the successful
      integration of the artificial skin. The present study combines the use of
      autologous adipose-derived stem cells with a commercially available dermal
      substitute (Integra) for skin regeneration. METHODS: Adipose-derived stem cells
      were isolated from the inguinal region of eight Sprague-Dawley adult rats, seeded
      onto a piece of dermal substitute for 48 hours, and then implanted into the same
      rat, followed by comparison of the evolution with a contralateral implant without
      adipose-derived stem cells. After 1, 2, and 3 weeks of regeneration in vivo,
      implants were removed for histologic evaluation. RESULTS: Adipose-derived stem
      cells adhere properly to the dermal matrix, and autologous tissue integration in
      the rat was good. The histologic evaluation showed that adipose-derived stem
      cells significantly increased microvascular density (7.7 +/- 0.6 percent versus
      5.3. +/- 0.5 percent, as assessed by immunohistochemical staining of factor VIII)
      and the synthesis of collagen type I (24 +/- 3 percent versus 16 +/- 2 percent,
      as assessed by Sirius red staining). Although there was greater epithelialization
      on the side treated with adipose-derived stem cells (2530 +/- 939 MUm versus 1911
      +/- 763 MUm), as assessed by anticytokeratin immunohistochemistry staining
      34betaE12, this difference was not statistically significant. CONCLUSIONS: The
      authors' data suggest that the seeding of adipose-derived stem cells onto a
      dermal substitute improves skin regeneration and tissue integration by increasing
      vascularity and collagen synthesis. Further studies are necessary to achieve
      complete epithelialization with the use of adipose-derived stem cells.

PMID- 22418721
TI  - Correcting upper eyelid retraction by means of pretarsal levator lengthening for
      complications following ptosis surgery.
AB  - BACKGROUND: Eyelid retraction is a condition in which the upper eyelid ascends
      past its ideal position, 1 to 2 mm below the upper limbus of the cornea. This
      condition can be a result of overcorrecting ptosis, hyperthyroidism, and other
      causes. The authors present studies conducted on eyelid retraction caused by
      ptosis overcorrection. An innovative approach for levator lengthening using the
      pretarsal tissue as a spacer flap is introduced as a method to correct the
      retraction. METHODS: A series of 60 patients over a 6-year period underwent 71
      eyelid procedures to correct upper lid retraction following upper blepharoplasty
      and ptosis repair. All eyelid retractions ranged from 1 to 3 mm above its ideal
      position. All eyelids were corrected with the authors' technique of lengthening
      the levator with pretarsal tissue. Twelve cases that required further lengthening
      were completed by creating a superiorly based rotation flap. RESULTS: Of the 71
      cases, 61 (86 percent) observed favorable results, six (8 percent) attained mild
      ptosis after surgery, and four (6 percent) regained upper eyelid retraction. All
      of the unsuccessful cases were corrected through early revision surgery, more
      advancement for the ptosis, and further recess or rotation flap for the
      retraction. No other complications were observed, except formation of supratarsal
      fold asymmetry, which was corrected through minor revision surgery. CONCLUSIONS:
      It is very difficult to correct eyelid retraction caused by tissue fibrosis and
      muscle degeneration. Correction of the retraction by levator lengthening using
      the pretarsal tissue is simpler to execute, measurable during surgery, and easy
      to adjust, and offers high predictability in its result. CLINICAL QUESTION/LEVEL
      OF EVIDENCE: Therapeutic, IV.

PMID- 22418722
TI  - Electromyographic analysis of trunk-muscle activity during stable, unstable and
      unilateral bridging exercises in healthy individuals.
AB  - BACKGROUND: Spinal pain can result in unilateral atrophy of spinal muscles.
      Understanding side-to-side muscle activity during exercises can help clinicians
      address these deficits. This study determined if variations of bridging exercises
      specifically activated side-to-side trunk-muscle activity. METHOD: Using surface
      electromyography on 20 healthy subjects (16 females), age 25.45 (+/- 3.57) years,
      height 166 (+/- 0.8) cm, weight 63.35 (+/- 12.70) kg, muscle activity of left and
      right lumbar multifidus, iliocostalis lumborum thoracis (ICLT), rectus abdominis
      (RA) and external oblique (EO) was recorded during eight bridging exercises with
      stable, unstable and unilateral (left-leg off the ground) conditions. RESULTS:
      There were significant side-to-side differences in abdominal-muscle activity
      during all unstable exercises (mean difference range from 3.10 %MVC for RA to
      9.86 %MVC for EO), and during all unilateral exercises (mean difference range
      from 3.22 %MVC for RA to 9.41 %MVC for EO), with the exception of RA in exercise
      7. For the back muscles, there were significant side-to-side differences for
      multifidus during all unilateral exercises (mean difference range 5.35 %MVC to
      11.72 %MVC), with the exception of exercise-5. None of the bilateral exercises
      (stable or unstable) produced side-to-side differences for multifidus. For ICLT
      only exercise-3 produced significant side-to-side differences with a mean
      difference of 5.5 %MVC. In all cases where significant differences were noted,
      the left side of the muscles demonstrated the higher values. CONCLUSION: The
      results suggest that specific exercises (unilateral/unstable) can target specific
      sides of trunk muscles.

PMID- 22418723
TI  - Findings, diagnoses and results of a halitosis clinic over a seven year period.
AB  - Halitosis or bad breath is a taboo subject that is a widespread problem in the
      general population. Causes of bad breath can be multifactorial and long time
      sufferers can be marred from deep psychological stress. Because nine out of ten
      cases have an oral cause, the initial inquiry should be with a dentist. In a
      retrospective study from February 2003 to February 2010, the halitosis clinic at
      the University of Basel analyzed data from 465 patient medical histories. Study
      objectives evaluated the causes of halitosis, gender distribution and treatment
      success. All patients reported to have suffered from bad breath. However, 82.7%
      were actually diagnosed as having halitosis. Within this group, 96.2% showed an
      oral etiology and 3.8% showed an extra-oral cause. Women suffered significantly
      more from psychogenic halitosis. Success rates of 92.6% subjectively and 94.5%
      objectively reflect the treatment success of the diagnostic and therapeutic
      concepts presented at the University of Basel halitosis clinic over a seven year
      period.

PMID- 22418724
TI  - Mouse models for Chikungunya virus: deciphering immune mechanisms responsible for
      disease and pathology.
AB  - Chikungunya virus (CHIKV), an alphavirus, has been responsible for large epidemic
      outbreaks with serious economic and social impact during the last 6 years.
      Transmitted by Aedes mosquitoes, it causes Chikungunya fever, an acute illness in
      patients with a stooped posture often associated with chronic and incapacitating
      arthralgia. The unprecedented re-emergence has stimulated renewed interest in
      CHIKV. This review discusses the advantages and disadvantages of different animal
      models for CHIKV infections and their importance to study the role of the immune
      system in different pathologies caused by CHIKV. We also reveal how such studies
      still present a difficult challenge, but are indispensible for mechanistic
      studies to further understand the pathophysiology of CHIKV infections.

PMID- 22418725
TI  - Immune modulation of inflammatory conditions: regulatory T cells for treatment of
      GvHD.
AB  - The immune system is a highly balanced network of different cell types. This
      balance is disturbed in the setting of organ or stem cell transplantation, which
      can lead to graft rejection or "Graft versus host disease" (GvHD). Conventional
      pharmacological treatment by broad immune suppression is restricted by dose
      limiting side effects. A novel strategy for prevention and control is cell
      therapy. This applies particularly to GvHD. A number of phase I trials have
      already been launched. The most appropriate cell type appears to be the
      regulatory T (Treg) cell as it is a natural "suppressor" of the immune system.
      Treg cells are able to inhibit various effector cells including CD4+ and CD8+ T
      cells, the main drivers of GvHD. Like other T cells, also Treg cells can be
      divided into naive and memory-type cells. We have previously identified
      effector/memory Treg cells (T(REM)), the regulatory counterparts of CD4+
      effector/memory T cells (T(EM)). T(REM) may be particularly suited to inhibit
      proinflammatory reactions in peripheral tissues as they express the chemokine
      receptor CCR6, a feature they share with proinflammatory Th17 cells. As specific
      marker, they also express CD39 but lack the expression of CD49d and CD127. We
      could show that a simple depletion of CD49d and CD127 expressing cells yields a
      population of "untouched" Treg cells that is highly pure and largely consist of
      highly suppressive T(REM) cells. Mouse models have confirmed the efficacy of Treg
      cells in controlling GvHD but the translation has been lagging. First clinical
      trials suggesting safety of adoptive Treg transfer increase the need for methods
      that allow obtaining clinical-grade Treg cells in sufficient amounts. The new
      approach may therefore provide a promising new alternative to facilitate a simple
      access to these cells.

PMID- 22418726
TI  - Dendritic cells and the malaria pre-erythrocytic stage.
AB  - Malaria remains one of the main infectious diseases in intertropical regions. The
      malaria parasite has a complex life cycle in its mammalian host, switching
      between variable forms as it traverses through different tissues and anatomic
      locations, either intra- or intercellularly. During its journey, the parasite
      encounters and interacts with the host immune system, which functions to prevent
      infections and limit ensuing pathologies. One important component of the host
      immune system is the dendritic cells (DC) network. DC form a heterogeneous group
      of pathogen-sensing and antigen-presenting cells that play a crucial role in the
      initiation of adaptive immunity. Here, we review the known and unknown
      interactions between the malaria parasites and the DC system, starting from the
      inoculation of the parasite in the skin up to its exit from the liver, also known
      as the pre-erythrocytic stage of the infection, and discuss how deciphering these
      interactions may contribute to our understanding of the Plasmodium parasite
      biology as well as to the induction of immune protection via vaccination.

PMID- 22418727
TI  - The roles of Galectin-3 in autoimmunity and tumor progression.
AB  - Galectin-3, a unique chimera-type member of the beta-galactoside-binding soluble
      lectin family, is widely expressed in numerous cells. Here, we discuss the role
      of Galectin-3 in T-cell-mediated inflammatory (auto) immunity and tumor rejection
      by using Galectin-3-deficient mice and four disease models of human pathology:
      experimental autoimmune encephalomyelitis (EAE), Con-A-induced hepatitis,
      multiple low-dose streptozotocin-induced diabetes (MLD-STZ diabetes) and
      metastatic melanoma. We present evidence which suggest that Galectin-3 plays an
      important pro-inflammatory role in Con-A-induced hepatitis by promoting the
      activation of T lymphocytes, NKT cells and DCs, cytokine secretion, prevention of
      M2 macrophage polarization and apoptosis of mononuclear cells, and it leads to
      severe liver injury. In addition, experiments in Galectin-3-"knock-out" mice
      indicate that Galectin-3 is also involved in immune-mediated beta-cell damage and
      is required for diabetogenesis in MLD-STZ model by promoting the expression of
      IFN-gamma, TNF-alpha, IL-17 and iNOS in immune and accessory effector cells.
      Next, our data demonstrated that Galectin-3 plays an important disease
      exacerbating role in EAE through its multifunctional roles in preventing cell
      apoptosis and increasing IL-17 and IFN-gamma synthesis, but decreasing IL-10
      production. Finally, based on our findings, we postulated that expression of
      Galectin-3 in the host may also facilitate melanoma metastasis by affecting tumor
      cell adhesion and modulating anti-melanoma immune response, in particular innate
      antitumor immunity. Taken together, we discuss the evidence of pro-inflammatory
      and antitumor activities of Galectin-3 and suggest that Galectin-3 may be an
      important therapeutic target.

PMID- 22418729
TI  - An innovative portfolio of research training programs for medical students.
AB  - Medical student education continues to evolve, with an increasing emphasis on
      evidence-based decision making in clinical settings. Many schools are introducing
      scholarly programs to their curriculum in order to foster the development of
      critical thinking and analytic skills, encourage self-directed learning, and
      develop more individualized learning experiences. In addition, participation in
      rigorous scholarly projects teaches students that clinical care and research
      should inform each other, with the goal of providing more benefit to patients and
      society. Physician-scientists, and physicians who have a better appreciation of
      science, have the potential to be leaders in the field who will deliver
      outstanding clinical care, contribute new knowledge, and educate their patients.

PMID- 22418728
TI  - Macrophage polarization and plasticity in health and disease.
AB  - The role of myelomonocytic cells like monocytes and macrophages as first line of
      host defense is well established. Recent understanding of these cells using
      systems biology, transgenesis and in disease models has brought them to a center
      stage in orchestrating crucial functions during homeostasis and pathogenesis.
      Thus, understanding the functional diversity of these cells in health and disease
      as well as the mechanisms that control these events would be crucial for
      designing strategies for regulating disease and reinstate homeostasis.

PMID- 22418730
TI  - Inhibition of acetylcholinesterase by green and white tea and their simulated
      intestinal metabolites.
AB  - By 2034 it is forecast that 5% of the global population will be aged 85 years or
      over--approximately two and half fold increase on present day figures--which will
      inevitably lead to an increase in age-associated disorders such as Alzheimer's
      disease. There is mounting evidence that green tea (Camellia sinensis) possesses
      numerous health-promoting properties, and may potentially be beneficial to those
      suffering from Alzheimer's and other diseases, including cardiovascular disease
      and cancer. These beneficial properties are largely attributed to the high
      polyphenol content, particularly the catechins. In this study, we measured
      acetylcholinesterase inhibition by white and green teas and their simulated
      intestinal digests. We found that the potency with which the white and green tea
      extracts inhibited acetylcholinesterase varied through the simulated digestion
      procedure. Initially, in the undigested extract form, potency was high with IC50
      values of 7.20 MUg mL-1 and 8.06 MUg mL-1 for green and white tea
      respectively.However, this decreased significantly after gastric digestion but
      activity was recovered after pancreatic digestion which could be related to
      relative increases in the levels of caffeine and specific phenolic components. Of
      the pure tea compounds tested, EGCG was the most potent with an IC50 of 0.0096
      MUmol mL-1 but its breakdown product; gamma-valerolactone was the least potent
      analyte. Particularly interesting were the results of caffeine,which exhibited a
      strong inhibitory activity and pyrogallol, which recorded a much stronger potency
      than its parent compound gallic acid, suggesting a pro-drug-like relationship.
      Overall, the results indicate that further research is necessary to determine the
      full potential of digestion of tea and its metabolites and how inter-individual
      variation may indicate that some sections of society could potentially benefit
      more from drinking tea as a strategy to prevent the development of dementia. We
      have also shown the activities of a number of metabolites,however, further
      research is required to determine their potential bioavailability.

PMID- 22418731
TI  - Eating high fat chow enhances the locomotor-stimulating effects of cocaine in
      adolescent and adult female rats.
AB  - RATIONALE: Dopamine systems vary through development in a manner that can impact
      drugs acting on those systems. Dietary factors can also impact the effects of
      drugs acting on dopamine systems. OBJECTIVES: This study examined whether eating
      high fat chow alters locomotor effects of cocaine (1-56 mg/kg) in adolescent and
      adult female rats. METHODS: Cocaine was studied in rats (n = 6/group) with free
      access to standard (5.7% fat) or high fat (34.3%) chow or restricted access to
      high fat chow (body weight matched to rats eating standard chow). RESULTS: After
      1 week of eating high fat chow (free or restricted access), sensitivity to
      cocaine was significantly increased in adolescent and adult rats, compared with
      rats eating standard chow. Sensitivity to cocaine was also increased in
      adolescent rats with restricted, but not free, access to high fat chow for 4
      weeks. When adolescent and adult rats that previously ate high fat chow ate
      standard chow, sensitivity to cocaine returned to normal. In adolescent and adult
      female rats eating high fat chow, but not those eating standard chow, sensitivity
      to cocaine increased progressively over once weekly tests with cocaine (i.e.,
      sensitization) in a manner that was not statistically different between
      adolescents and adults. CONCLUSIONS: These results show that eating high fat chow
      alters sensitivity of female rats to acutely administered cocaine and also
      facilitates the development of sensitization to cocaine. That the type of food
      consumed can increase drug effects might have relevance to vulnerability to abuse
      cocaine in the female population.

PMID- 22418733
TI  - Genetic analysis of LRRK2 A419V variant in ethnic Chinese.
AB  - Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the most common
      causes of autosomal dominant and sporadic forms of Parkinson's disease (PD). The
      A419V variant has been suggested to be a potential risk variant but its role
      among Chinese is unclear. We genotyped LRRK2 A419V variant to investigate the
      association with risk of PD. A total of 1314 subjects comprising 729 patients
      with PD and 585 controls were genotyped. Twenty-two (3.0%) patients were
      heterozygous carriers for the A419V variant, and the frequency was higher
      compared with controls (0.7%, p = 0.003). The association was seen among the
      younger age group (early onset PD patients vs. controls: p = 0.0005), but was not
      significant among the older age group (late onset PD patients vs. controls: p =
      0.17). We showed a significant association of LRRK2 A419V variant among early
      onset PD in the ethnic Han Chinese population but not among late onset PD.
      Further replication studies in additional Chinese and other Asian cohorts will be
      important to address its potential pathophysiologic role.

PMID- 22418732
TI  - Effects of the combination of metyrapone and oxazepam on intravenous nicotine
      self-administration in rats.
AB  - RATIONALE: Despite increased education regarding its dangers, cigarette smoking
      remains a significant public health concern due to serious associated health
      consequences such as cancer and respiratory and cardiovascular diseases. Most
      smokers fail in their attempts to quit smoking, and current pharmacological
      interventions have relatively low levels of efficacy and are associated with
      significant adverse events. We have previously reported that combinations of
      metyrapone and oxazepam, administered at doses that were ineffective when
      delivered singly, resulted in dose-related decreases in cocaine self
      administration in rats while not affecting food-maintained responding during the
      same sessions. OBJECTIVES: The current study was designed to test the effects of
      the administration of a metyrapone:oxazepam combination on nicotine self
      administration in rats. METHODS: Several dose combinations of metyrapone (12.5,
      25 or 50 mg/kg) and oxazepam (5 or 10 mg/kg) were tested in rats trained to
      intravenously (IV) self-administer nicotine (0.03 mg/kg/infusion) during 1-h self
      administration sessions using both fixed-ratio and progressive-ratio (PR)
      schedules of reinforcement. RESULTS: The administration of low doses of
      metyrapone and oxazepam in combination significantly decreased IV nicotine self
      administration in rats. At the lowest doses of 12.5 mg/kg of metyrapone and 5
      mg/kg of oxazepam, the drugs alone did not decrease IV nicotine self
      administration, but the combination was effective. Varenicline was also tested
      using the fixed-ratio schedule, and reductions in nicotine intake were similar to
      those seen with the moderate dose of the combination. CONCLUSIONS: The results of
      this study suggest a potential utility of the combination of metyrapone and
      oxazepam for smoking cessation in humans.

PMID- 22418735
TI  - Diffusion tensor MRI contributes to differentiate Richardson's syndrome from PSP
      parkinsonism.
AB  - This study investigated the regional distribution of white matter (WM) damage in
      Richardson's syndrome (PSP-RS) and progressive supranuclear palsy-Parkinsonism
      (PSP-P) using diffusion tensor (DT) magnetic resonance imaging (MRI). The DT MRI
      classificatory ability in diagnosing progressive supranuclear palsy (PSP)
      syndromes, when used in combination with infratentorial volumetry, was also
      quantified. In 37 PSP (21 PSP-RS, 16 PSP-P) and 42 controls, the program Tract
      Based Spatial Statistics (TBSS; www.fmrib.ox.ac.uk/fsl/tbss) was applied. DT MRI
      metrics were derived from supratentorial, thalamic, and infratentorial tracts.
      The magnetic resonance parkinsonism index (MRPI) was calculated. All PSP harbored
      diffusivity abnormalities in the corpus callosum, frontoparietal, and
      frontotemporo-occipital tracts. Infratentorial WM and thalamic radiations were
      severely affected in PSP-RS and relatively spared in PSP-P. When MRPI and DT MRI
      measures were combined, the discriminatory power increased for each comparison.
      Distinct patterns of WM alterations occur in PSP-RS and PSP-P. Adding DT MRI
      measures to MRPI improves the diagnostic accuracy in differentiating each PSP
      syndrome from healthy individuals and each other.

PMID- 22418734
TI  - C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS population.
AB  - It has been recently reported that a large proportion of patients with familial
      amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are
      associated with a hexanucleotide (GGGGCC) repeat expansion in the first intron of
      C9ORF72. We have assessed 1757 Italian sporadic ALS cases, 133 from Sardinia, 101
      from Sicily, and 1523 from mainland Italy. Sixty (3.7%) of 1624 mainland Italians
      and Sicilians and 9 (6.8%) of the 133 Sardinian sporadic ALS cases carried the
      pathogenic repeat expansion. None of the 619 regionally matched control samples
      (1238 chromosomes) carried the expansion. Twenty-five cases (36.2%) had
      behavioral FTD in addition to ALS. FTD or unspecified dementia was also detected
      in 19 pedigrees (27.5%) in first-degree relatives of ALS patients. Cases carrying
      the C9ORF72 hexanucleotide expansion survived 1 year less than cases who did not
      carry this mutation. In conclusion, we found that C9ORF72 hexanucleotide repeat
      expansions represents a sizeable proportion of apparent sporadic ALS in the
      Italian and Sardinian population, representing by far the most common mutation in
      Italy and the second most common in Sardinia.

PMID- 22418736
TI  - Transcriptional control of cell cycle-dependent kinase 4 by Smad proteins-
      implications for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by
      deregulation of neuronal cell cycle and differentiation control eventually
      resulting in cell death. During brain development, neuronal differentiation is
      regulated by Smad proteins, which are elements of the canonical transforming
      growth factor beta (TGF-beta) signaling pathway, linking receptor activation to
      gene expression. In the normal adult brain, Smad proteins are constitutively
      phosphorylated and predominantly localized in neuronal nuclei. Under
      neurodegenerative conditions such as AD, the subcellular localization of their
      phosphorylated forms is heavily disturbed, raising the question of whether a
      nuclear Smad deficiency in neurons might contribute to a loss of neuronal
      differentiation control and subsequent cell cycle re-entry. Here, we show by
      luciferase reporter assays, electromobility shift, and RNA interference (RNAi)
      technique a direct binding of Smad proteins to the CDK4 promoter inducing
      transcriptional inhibition of cell cycle-dependent kinase 4 (Cdk4). Mimicking the
      neuronal deficiency of Smad proteins observed in AD in cell culture by RNAi
      results in elevation of Cdk4 and retardation of neurite outgrowth. The results
      identify Smad proteins as direct transcriptional regulators of Cdk4 and add
      further evidence to a Smad-dependent deregulation of Cdk4 in AD, giving rise to
      neuronal dedifferentiation and cell death.

PMID- 22418737
TI  - Identifying major depression using whole-brain functional connectivity: a
      multivariate pattern analysis.
AB  - Recent resting-state functional connectivity magnetic resonance imaging studies
      have shown significant group differences in several regions and networks between
      patients with major depressive disorder and healthy controls. The objective of
      the present study was to investigate the whole-brain resting-state functional
      connectivity patterns of depressed patients, which can be used to test the
      feasibility of identifying major depressive individuals from healthy controls.
      Multivariate pattern analysis was employed to classify 24 depressed patients from
      29 demographically matched healthy volunteers. Permutation tests were used to
      assess classifier performance. The experimental results demonstrate that 94.3% (P
      < 0.0001) of subjects were correctly classified by leave-one-out cross
      validation, including 100% identification of all patients. The majority of the
      most discriminating functional connections were located within or across the
      default mode network, affective network, visual cortical areas and cerebellum,
      thereby indicating that the disease-related resting-state network alterations may
      give rise to a portion of the complex of emotional and cognitive disturbances in
      major depression. Moreover, the amygdala, anterior cingulate cortex,
      parahippocampal gyrus and hippocampus, which exhibit high discriminative power in
      classification, may play important roles in the pathophysiology of this disorder.
      The current study may shed new light on the pathological mechanism of major
      depression and suggests that whole-brain resting-state functional connectivity
      magnetic resonance imaging may provide potential effective biomarkers for its
      clinical diagnosis.

PMID- 22418738
TI  - Exploiting the glioblastoma peptidome to discover novel tumour-associated
      antigens for immunotherapy.
AB  - Peptides presented at the cell surface reflect the protein content of the cell;
      those on HLA class I molecules comprise the critical peptidome elements
      interacting with CD8 T lymphocytes. We hypothesize that peptidomes from ex vivo
      tumour samples encompass immunogenic tumour antigens. Here, we uncover >6000 HLA
      bound peptides from HLA-A*02(+) glioblastoma, of which over 3000 were restricted
      by HLA-A*02. We prioritized in-depth investigation of 10 glioblastoma-associated
      antigens based on high expression in tumours, very low or absent expression in
      healthy tissues, implication in gliomagenesis and immunogenicity. Patients with
      glioblastoma showed no T cell tolerance to these peptides. Moreover, we
      demonstrated specific lysis of tumour cells by patients' CD8(+) T cells in vitro.
      In vivo, glioblastoma-specific CD8(+) T cells were present at the tumour site.
      Overall, our data show the physiological relevance of the peptidome approach and
      provide a critical advance for designing a rational glioblastoma immunotherapy.
      The peptides identified in our study are currently being tested as a multipeptide
      vaccine (IMA950) in patients with glioblastoma.

PMID- 22418739
TI  - Oxidative stress and successful antioxidant treatment in models of RYR1-related
      myopathy.
AB  - The skeletal muscle ryanodine receptor is an essential component of the
      excitation-contraction coupling apparatus. Mutations in RYR1 are associated with
      several congenital myopathies (termed RYR1-related myopathies) that are the most
      common non-dystrophic muscle diseases of childhood. Currently, no treatments
      exist for these disorders. Although the primary pathogenic abnormality involves
      defective excitation-contraction coupling, other abnormalities likely play a role
      in disease pathogenesis. In an effort to discover novel pathogenic mechanisms, we
      analysed two complementary models of RYR1-related myopathies, the relatively
      relaxed zebrafish and cultured myotubes from patients with RYR1-related
      myopathies. Expression array analysis in the zebrafish disclosed significant
      abnormalities in pathways associated with cellular stress. Subsequent studies
      focused on oxidative stress in relatively relaxed zebrafish and RYR1-related
      myopathy myotubes and demonstrated increased oxidant activity, the presence of
      oxidative stress markers, excessive production of oxidants by mitochondria and
      diminished survival under oxidant conditions. Exposure to the antioxidant N
      acetylcysteine reduced oxidative stress and improved survival in the RYR1-related
      myopathies human myotubes ex vivo and led to significant restoration of aspects
      of muscle function in the relatively relaxed zebrafish, thereby confirming its
      efficacy in vivo. We conclude that oxidative stress is an important
      pathophysiological mechanism in RYR1-related myopathies and that N-acetylcysteine
      is a successful treatment modality ex vivo and in a vertebrate disease model. We
      propose that N-acetylcysteine represents the first potential therapeutic strategy
      for these debilitating muscle diseases.

PMID- 22418741
TI  - Electrical and optical properties of InP nanowire ensemble p+-i-n+
      photodetectors.
AB  - We report on a comprehensive study of electrical and optical properties of
      efficient near-infrared p+-i-n+ photodetectors based on large ensembles of self
      assembled, vertically aligned i-n+ InP nanowires monolithically grown on a common
      p+ InP substrate without any buffer layer. The nanowires have a polytype
      modulated crystal structure of wurtzite and zinc blende. The electrical data
      display excellent rectifying behavior with an ideality factor of about 2.5 at 300
      K. The ideality factor scales with 1/T, which possibly reflects deviations from
      classical transport models due to the mixed crystal phase of the nanowires. The
      observed dark leakage current is of the order of merely ~100 fA/nanowire at 1 V
      reverse bias. The detectors display a linear increase of the photocurrent with
      reverse bias up to about 10 pA/nanowire at 5 V. From spectrally resolved
      measurements, we conclude that the photocurrent is primarily generated by
      funneling photogenerated carriers from the substrate into the NWs. Contributions
      from direct excitation of the NWs become increasingly important at low
      temperatures. The photocurrent decreases with temperature with an activation
      energy of about 50 meV, which we discuss in terms of a temperature-dependent
      diffusion length in the substrate and perturbed transport through the mixed-phase
      nanowires.

PMID- 22418740
TI  - Enabling global processing in simultanagnosia by psychophysical biasing of visual
      pathways.
AB  - A fundamental aspect of visual cognition is our disposition to see the 'forest
      before the trees'. However, damage to the posterior parietal cortex, a critical
      brain region along the dorsal visual pathway, can produce a neurological disorder
      called simultanagnosia, characterized by a debilitating inability to perceive the
      'forest' but not the 'trees' (i.e. impaired global processing despite intact
      local processing). This impairment in perceiving the global shape persists even
      though the ventral visual pathway, the primary recognition pathway, is intact in
      these patients. Here, we enabled global processing in patients with
      simultanagnosia using a psychophysical technique, which allowed us to bias
      stimuli such that they are processed predominantly by the intact ventral visual
      pathway. Our findings reveal that the impairment in global processing that
      characterizes simultanagnosia stems from a disruption in the processing of low
      spatial frequencies through the dorsal pathway. These findings advance our
      understanding of the relationship between visuospatial attention and perception
      and reveal the neural mechanism mediating the disposition to see the 'forest
      before the trees'.

PMID- 22418742
TI  - Pathways involved in Drosophila and human cancer development: the Notch,
      Hedgehog, Wingless, Runt, and Trithorax pathway.
AB  - Animal models are established tools to study basic questions of biology in a
      systematic way. They have greatly facilitated our understanding of the mechanisms
      by which nature forms and maintains organisms. Much of the knowledge on molecular
      changes underlying the development of organisms originates from research in the
      fruit fly model Drosophila melanogaster. Vertebrate models including the mouse
      and zebrafish model, but also other animal models coming from different corners
      of the animal kingdom have shown that much of the basic machinery of development
      is essentially identical, not just in all vertebrates but in all major phyla of
      invertebrates too. Moreover, key elements of this machinery have been
      demonstrated to be involved in recurrent molecular abnormalities detected in
      tumor-tissue from patients, indicating their implication in the genesis of human
      cancer. Thus, research in this field has become a common topic for both
      biologists and hemato-oncologists. In this review, we summarize current knowledge
      on some of these key elements and molecular pathways such as Notch, Hedgehog,
      Wingless, Runt, and Trithorax that have been originally described and studied in
      animal models and which seem to play a major role in the pathophysiology and
      targeted management of human cancer.

PMID- 22418743
TI  - Baseline predictors of response to TNF-alpha blocking therapy in ankylosing
      spondylitis.
AB  - PURPOSE OF REVIEW: Identifying the characteristics of patients with ankylosing
      spondylitis (AS) before start of treatment which are able to predict a beneficial
      response to tumor necrosis factor-alpha (TNF-alpha) blocking therapy is relevant,
      especially in view of the high costs and potential side-effects of these agents.
      This review provides an overview of clinical trials and observational studies
      investigating baseline predictors of response after 3-6 months of TNF-alpha
      blocking therapy and baseline predictors of long-term anti-TNF-alpha treatment
      continuation in AS. RECENT FINDINGS: In multiple studies, increased acute phase
      reactants, higher disease activity, higher functional status, younger age, and
      HLA-B27 positivity were identified as independent baseline predictors of
      achieving clinical response to TNF-alpha blocking therapy. Increased acute phase
      reactants, presence of peripheral arthritis, and male sex were repeatedly
      identified as independent baseline predictors of anti-TNF-alpha treatment
      continuation. SUMMARY: Several studies using multivariate analyses identified
      comparable baseline predictors of response and/or continuation of TNF-alpha
      blocking therapy. The single predictors identified have, at best, moderate
      capacity to predict treatment response in the individual patient. The development
      of a prediction model may lead to a more robust instrument to support physicians
      in decision making on TNF-alpha blocking therapy in AS in daily clinical
      practice.

PMID- 22418744
TI  - Changing winds in refractory autoimmune disease in children:  clearing the road
      for tolerance with cellular therapies.
AB  - PURPOSE OF REVIEW: To give an overview of the recent advances in cellular
      therapies in pediatric autoimmune diseases. RECENT FINDINGS: Since the 1990s,
      autologous hematopoietic stem cell transplantation (HSCT) has been applied in
      more than 800 patients with severe refractory autoimmune diseases. Despite
      obvious successes, it is clear that the autoimmune disease in many of these
      patients relapsed. Anecdotal reports of allogeneic HSCT seem promising.
      Furthermore, several trials exploring the use of mesenchymal stem or stromal
      cells (MSC) for therapy of refractory autoimmune diseases have been published.
      Mostly allogeneic MSC are used at a dose of 1 million/kg intravenously. SUMMARY:
      Even though promising new agents have become available for the treatment of
      autoimmune disease (AID), some arthritis patients fail to achieve even a modest
      improvement. Cellular therapies may be the answer in steering the immune system
      into a more tolerant path. Autologous HSCT after an immunoablative pretreatment
      allows rebuilding of a partially reset immune system. A small group of severely
      refractory pediatric patients is unlikely to benefit from immunosuppressive
      therapies alone. With allogeneic transplant becoming safer and overall mortality
      numbers much lower in pediatric transplantation, allogeneic HSCT might become the
      more sensible option for this small group of refractory patients. A promising new
      cellular therapy is the use of MSC. The working mechanism is immunomodulatory,
      through induction of Tregs. Although their place is still to be determined, they
      may provide a safer alternative to severely compromised children or as an
      adjuvant therapy earlier in the disease. We have implemented cellular therapy
      options for our refractory pediatric AID patients. We consider progressing to
      cellular therapies in severely affected individuals, to ultimately cure their
      disease. Our cellular therapy protocols are provided in this review.

PMID- 22418745
TI  - Rectal perforation with life-threatening peritonitis following stapled
      haemorrhoidopexy.
AB  - BACKGROUND: Stapled haemorrhoidopexy is a well recognized alternative to
      haemorrhoidectomy, and is associated with reduced pain and earlier return to
      normal activity. This paper reports all published cases of life-threatening
      sepsis following stapled haemorrhoidopexy, identifies causative factors and makes
      recommendations. METHODS: A systematic review of the literature was performed by
      searching the major electronic databases. All relevant references were reviewed
      for possible inclusion. All references of the relevant articles were screened for
      any further articles that were not identified in the initial search. RESULTS:
      From 2000 to the present, 29 articles reporting complications in 40 patients were
      identified. Thirty-five patients underwent laparotomy with faecal diversion and a
      further patient was treated by low anterior resection. A specific complication
      was rectal perforation with peritonitis. Factors that led to life-threatening
      sepsis were identified in 30 patients. Despite surgical treatment and
      resuscitation, there were four deaths. CONCLUSION: Severe sepsis can complicate
      stapled haemorrhoidopexy. Rectal perforation and peritonitis are a particular
      risk of this technique and the associated mortality rate is high.

PMID- 22418747
TI  - Serum C-reactive protein level and prehypertension in two Asian populations.
AB  - Few previous studies in Western populations have reported an association between
      C-reactive protein (CRP) and prehypertension. However, no previous study has
      examined this association in Asians. We examined individuals who were free of
      hypertension from two independent population-based studies in Singapore: the
      Singapore Prospective Study Programme (SP2, n=2843 Chinese, Malay and Indians
      aged ?24 years) and the Singapore Malay Eye Study (SiMES, n=957 Malays, aged 40
      80 years). Prehypertension was defined as systolic blood pressure (BP) 120-139 mm
      Hg or diastolic BP 80-89 mm Hg. CRP was analyzed as categories (<1, 1-3, >3 mg l(
      1)). The prevalence of prehypertension increased with increasing categories of
      CRP in both cohorts (P for trend <0.05 in both cohorts). After adjusting for
      potential confounders including body mass index (BMI), smoking and diabetes,
      persons with higher levels of CRP were more likely to have prehypertension in
      both SP2 (compared with CRP <1 mg l(-1), odds ratio (OR) 1.23, 95% confidence
      interval (CI) 1.03-1.48 for CRP 1-3 and OR 1.67, 95% CI 1.32-2.10 for >3 mg l(
      1)) and SiMES (OR 1.45, 95% CI 1.04-2.01 and OR 1.56, 95% CI 1.07-2.27)
      respectively. In conclusion, data from two population-based Asian cohorts suggest
      that elevated serum CRP levels are associated with prehypertension.

PMID- 22418748
TI  - Matrix metalloproteinases and their tissue inhibitors in hypertension-related
      pregnancy complications.
AB  - Matrix metalloproteinases (MMPs) are a family of endopeptidases that degrade the
      components of the extracellular matrix (ECM) such as collagen, and thus
      contribute to the remodelling and the physiological homeostasis of the ECM and
      its blood supply. The activities of these enzymes are regulated by endogenous
      tissue inhibitors of metalloproteinases (TIMPs), and it has been suggested that a
      balance between MMPs and TIMPs plays an important role in vascular remodelling,
      angiogenesis and vasodilatation in a number of physiological situations. It
      follows that, regarding a relationship between MMPs and TIMPs, an imbalance
      between these molecules may lead to pathology in a wide range of conditions,
      including hypertension, cancer and pulmonary disease, and in the pathophysiology
      of reproduction. Indeed, regarding the latter, abnormalities in the maternal
      peripheral vasculature have been proposed as being (partly) responsible for the
      effects of hypertension on pregnancy and the development of complications
      including pre-eclampsia and eclampsia. However, the associations between MMPs,
      TIMPs and disease may be simply of association, not of pathology. This brief
      review explores current literature on the role of abnormalities of the ECM in
      general, focusing on the pathogenesis of hypertension and its complications
      during pregnancy as a model of disordered angiogenesis and remodelling.

PMID- 22418749
TI  - HIV testing as a normal diagnostic procedure.

PMID- 22418750
TI  - Utility of desensitisation for allergy to antibiotics.
AB  - Immediate-type allergic reactions to medication are potentially life threatening
      and can hamper the drug therapy of several medical conditions. If no alternative
      drug treatment is available, a desensitisation procedure may secure the
      continuation of necessary therapy by inducing a temporal state of tolerance.
      Desensitisation is only appropriate in case of a strong suspicion of an IgE
      mediated allergic reaction. It should be performed by trained clinicians (allergy
      specialists) in a hospital setting where treatment of a potential anaphylactic
      reaction can be done without any delay. In this article, literature describing
      desensitisation procedures for several antibiotics is reviewed.

PMID- 22418751
TI  - Systemic vasculitis in myelodysplastic syndromes.
AB  - The development of immunological abnormalities in various neoplasms is a rather
      common phenomenon. The prevalence of life-threatening systemic vasculitis in
      malignancy, however, is much lower. Nonetheless we found an unexpected frequency
      of several autoimmune manifestations, including systemic vasculitis, in certain
      myelodysplastic syndromes. We illustrate this finding with the case of a 43-year
      old man with signs of polyarteritis nodosa-like systemic vasculitis during
      progression of chronic myelomonocytic leukaemia. Subsequently, we review the
      literature on the combination of myelodysplastic syndromes and systemic
      vasculitis and discuss the prognostic consequences, considerations for treatment
      and possible pathophysiological mechanisms.

PMID- 22418752
TI  - Delayed HIV testing in internal medicine clinics - a missed opportunity.
AB  - As HIV infection may be non-symptomatic for many years, many HIV-infected
      individuals are not aware of their infection. At a certain point in time non
      specific symptoms may occur for which patients are likely be referred to internal
      medicine outpatient clinics. In the absence of systematic screening for HIV and
      in particular in patients who do not have classical risk factors for HIV, the
      diagnosis of HIV infection may easily be overlooked. In this manuscript it is
      illustrated that this diagnostic and therapeutic delay can lead to increased
      morbidity and mortality. Moreover, undiagnosed individuals are on average more
      likely to transmit HIV than diagnosed individuals. It is important for public
      health to identify people harbouring HIV infection, as this is expected to reduce
      the number of new infections. HIV infection should be considered a possible cause
      of unexplained symptoms in an early stage of the diagnostic process, in
      particular in patients with symptoms such as unexplained fever, lymphadenopathy
      or weight loss or in the presence of conditions suggestive of possible immune
      deficiency, regardless of the absence of risk factors.

PMID- 22418753
TI  - Risk of cardiovascular events in patients with polycystic ovary syndrome.
AB  - Women with polycystic ovary syndrome (PCOS) have increased prevalence of
      cardiovascular (CV) risk factors. However, data on the incidence of CV events are
      lacking in this population. Using Rochester Epidemiology Project resources, we
      conducted a retrospective cohort study comparing CV events in women with PCOS
      with those of women without PCOS in Olmsted County, Minnesota. Between 1966 and
      1988, 309 women with PCOS and 343 without PCOS were identified. Mean (SD) age at
      PCOS diagnosis was 25.0 (5.3) years; mean age at last follow-up was 46.7 years.
      Mean (SD) follow-up was 23.7 (13.7) years. Women with PCOS had a higher body mass
      index (29.4 kg/m2 vs 28.3 kg/m2; p=.01). Prevalence of type 2 diabetes mellitus
      and hypertension and levels of total cholesterol, high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol and triglycerides were similar
      in the two groups. We observed no increase in CV events, including myocardial
      infarction (adjusted hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.32 to
      1.72; p=.48); coronary artery bypass graft surgery (adjusted HR 1.52; 95% CI 0.42
      to 5.48; p=.52); death (adjusted HR 1.03; 95% CI, 0.29 to 3.71; p=.96); death due
      to CV disease (adjusted HR 5.67; 95% CI 0.51 to 63.7; p=.16); or stroke (adjusted
      HR 1.05; 95% CI 0.28 to 3.92; p=.94). Although women with PCOS weighed more than
      controls, there was no increased prevalence of other CV risk factors.
      Furthermore, we found no increase in CV events. While prospective studies are
      needed to confirm these findings, women with PCOS do not appear to have adverse
      CV outcomes in midlife.

PMID- 22418754
TI  - Vasculitis revealed by posterior stroke.
AB  - Posterior ischaemic stroke is relatively uncommon, and its occurrence should
      alert clinicians to possible uncommon underlying disease. We report a patient
      with occipital brain infarction. The combination of age, gender, general malaise
      and elevated erythrocyte sedimentation rate led to the clinical suspicion of
      giant cell arteritis. Vertebral artery vasculitis was confirmed by 18-FD G
      positron emission tomography, combined with CT angiography, and immediate
      immunosuppressive therapy was started. Symptoms of stroke should, in a particular
      clinical context, raise suspicion of giant cell arteritis.

PMID- 22418755
TI  - Crystalluria.

PMID- 22418756
TI  - A leg with an ulcer.

PMID- 22418757
TI  - An Aruban man with fever, abdominal mass and eosinophilia.

PMID- 22418758
TI  - SWAB/NVALT (Dutch Working Party on Antibiotic Policy and Dutch Association of
      Chest Physicians) guidelines on the management of community-acquired pneumonia in
      adults.
AB  - The Dutch Working Party on Antibiotic Policy (SWAB) and the Dutch Association of
      Chest Physicians (NVALT) convened a joint committee to develop evidence-based
      guidelines on the diagnosis and treatment of community acquired pneumonia (CAP).
      The guidelines are intended for adult patients with CAP who present at the
      hospital and are treated as outpatients as well as for hospitalised patients up
      to 72 hours after admission. Areas covered include current patterns of
      epidemiology and antibiotic resistance of causative agents of CAP in the
      Netherlands, the possibility to predict the causative agent of CAP on the basis
      of clinical data at first presentation, risk factors associated with specific
      pathogens, the importance of the severity of disease upon presentation for choice
      of initial treatment, the role of rapid diagnostic tests in treatment decisions,
      the optimal initial empiric treatment and treatment when a specific pathogen has
      been identified, the timeframe in which the first dose of antibiotics should be
      given, optimal duration of antibiotic treatment and antibiotic switch from the
      intravenous to the oral route. Additional recommendations are made on the role of
      radiological investigations in the diagnostic work-up of patients with a clinical
      suspicion of CAP, on the potential benefit of adjunctive immunotherapy, and on
      the policy for patients with parapneumonic effusions.

PMID- 22418759
TI  - Transplacental passage of nevirapine, nelfinavir and lopinavir.

PMID- 22418760
TI  - Severe hypertriglyceridaemia associated with the use of capecitabine.

PMID- 22418761
TI  - Assessment of environmental health children's population living in environmental
      injustice scenarios.
AB  - We conducted a cross sectional study, involving 145 children randomly selected
      from three different socioeconomic locations. We selected social, environment and
      health indicators and measured the prevalence and prevalence odds ratios.
      Children from the brick producing site (segregation index 5), are exposed to high
      levels of multiple toxic agents, and showed the highest morbidity rates and
      malnutrition, anemia, dental fluorosis, and the lowest IQ, followed by children
      from municipal garbage dump (segregation index 4), where we detected the highest
      prevalence of dermatological and enteric diseases. Children from the Central Zone
      (segregation index 2) showed the lowest rates of malnutrition and higher IQ than
      the other two groups. A unified vision of social, health and environmental
      indicators opens the possibility of novel intervention programs and a legal
      framework that specifically protect children against environmental exposures.

PMID- 22418762
TI  - Low-medium resolution HLA-DQ2/DQ8 typing for coeliac disease predisposition
      analysis by colorimetric assay.
AB  - Coeliac disease is an inflammation of the small intestine, occurring in
      genetically susceptible individuals triggered by the ingestion of gluten. Human
      Leukocyte Antigens (HLA) DQ2 and DQ8 gene have been identified as key genetic
      factors in coeliac disease as they are presented in almost 100 % of the patients.
      These genes are encoded by the combination of certain alleles in the DQA and DQB
      region of chromosome 6. Specifically, DQA1*05:01 and DQB1*02:01 alleles for
      serologically defined leukocyte antigen DQ2 cis, DQA1*05:05 and DQB1*02:02 for
      DQ2 trans and DQA1*03:01 and DQB1*03:02 alleles for the DQ8. Specific
      identification of these alleles is a challenge due to the high number of alleles
      that have been identified so far: 46 in the DQA region and 160 in the DQB region
      (as of IMGT/HLA Database 10/2011 release). In the reported work, the development
      of a multiplex colorimetric assay for the low to medium HLA typing of the DQ2 and
      DQ8 genes is presented. The optimisation of probe design and assay conditions,
      performed by both surface plasmon resonance and enzyme-linked oligonucleotide
      assay, are reported. Finally, the performances of the developed typing platform
      were validated by the analysis of real patient samples and HLA typing, compared
      with those obtained using hospital based typing technology and an excellent
      correlation obtained.

PMID- 22418763
TI  - Is sampling transitional zone in patients who had prior negative prostate biopsy
      necessary?
AB  - OBJECTIVE: To assess the necessity of transitional zone sampling of the prostate
      during repeat prostate biopsy procedures. METHODS: Patients treated for lower
      urinary tract symptoms with transurethral resection of the prostate (TURP) from
      April 2004 to July 2009 whom had at least 1 negative prostate biopsy prior to
      this treatment were chosen as the study group. A histopathological analysis of
      surgical specimens was employed to determine cancer detection rates. RESULTS: A
      total of 72 patients with the mean age of 66.1, mean prostate-specific antigen
      (PSA) of 10.4 ng/mL and mean prostate volume of 63.2 cc were included. Of the
      patients, 50 had 1 biopsy set, 17 had 2 sets, 4 had 3 sets and 1 patient had 4
      sets of consecutive biopsies. All biopsy results were negative for prostate
      cancer. After the analysis of surgical specimens obtained during TURP, cancer was
      detected in 3 patients (4.2%). Transitional zone sampling during prostate
      biopsies did not significantly improve the cancer detection rate. Transitional
      zone sampling was performed in 29 biopsies taken from 20 patients, one of whom
      (5%) had prostate cancer. The remaining 71 biopsies were taken from 52 patients
      without transitional zone sampling, and cancer was detected in 2 (3.8%) of them.
      CONCLUSIONS: Since no significant difference was observed between patient groups
      (those with and those without transitional zone biopsies) in the detection of
      prostate cancer in the transitional zone, strategies for increasing the number of
      cores taken from transitional zone during repeat biopsies should be reconsidered.

PMID- 22418764
TI  - Low concentration of heparin used for permanent catheters canal locking is
      effective and diminishes the risk of bleeding.
AB  - PURPOSE: There is an increasing number of patients being dialyzed with permanent
      catheters (PC). In the majority of cases, heparin is used to maintain PC patency.
      This practice causes clotting disturbances due to heparin leakage and may
      predispose the patient to bleeding episodes. It has not been well studied whether
      lowering heparin concentration for canal locking decreases short-term bleeding
      complications after PC placement. METHODS: This was a prospective single-center
      randomized open-label trial conducted in hemodialyzed patients undergoing PC
      insertion. Low concentration of heparin (LCH) 2,500 IU/ml versus high
      concentration of heparin (HCH) 5,000 IU/ml was randomly used for catheter lumens
      locking. The primary endpoint was the occurrence of bleeding within 24 h after
      catheter placement. The effects of clinical and laboratory data on bleeding
      events were analyzed as secondary endpoints. RESULTS: Seventy-five patients (37
      in LCH) were enrolled in the study. Only in the HCH group we found a significant
      prolongation of activated partial thromboplastin time (APTT) 2 h after PC
      placement (p < 0.001). There was a higher number of bleeding episodes in the HCH
      group (n = 16; 42.1%) than in the LCH group (n = 7; 18.9%) (chi(2) = 4.74; p =
      0.029). In univariate analysis, assignment to HCH, baseline APTT, use of low
      molecular weight heparin, and femoral localization were associated with bleeding
      events. In multivariate analysis, the use of HCH (odds ratio [OR] 3.64; 95%
      confidence interval [95% CI] 1.10-12.05) and baseline APTT (OR 1.12; 95% CI 1.002
      1.250) predicted bleeding after PC insertion. CONCLUSION: LCH used for canals
      locking decreases bleeding events in the first 24 hours after permanent catheter
      placement, compared to HCH.

PMID- 22418765
TI  - Pregnancy in women with Alport syndrome.
AB  - BACKGROUND: Little is known about pregnancy in women with Alport syndrome (AS),
      as only four cases have been reported in the literature. We herein describe the
      course of pregnancy in two sisters with overt forms of AS. CASES: Both women were
      diagnosed as having autosomal recessive AS. Before pregnancy, their renal
      function and their blood pressure were normal, and proteinuria values were below
      2 g/24 h. Both patients faced a progressive and remarkable increase in
      proteinuria during pregnancy, with subsequent hypoproteinemia. The clinical
      condition worsened, particularly in the first case, who was managed with some
      success with a combination of diuretics. She delivered at 32 weeks of pregnancy.
      The second patient was less challenging and she delivered at 36 weeks.
      Proteinuria returned to pre-pregnancy levels in both cases, after delivery.
      CONCLUSION: Management of pregnant women with overt AS is challenging and
      worsening of renal disease has to be expected. The use of diuretic therapy may be
      of benefit.

PMID- 22418766
TI  - The FDA outlook of events reporting after ticagrelor or clopidogrel in the PLATO
      Trial: impact of sponsor censoring dates, drug discontinuation, and withdrawal of
      consent.
AB  - BACKGROUND: Censoring by the study sponsor of clinical endpoint events in
      indication-seeking randomized trials represents a controversial approach since
      the reported data may be biased in favor of experimental agents due to the
      obvious conflict of interest. The frequency of drug discontinuation and rates of
      consent withdrawal may also impact the trial outcomes. PURPOSE: To assess
      patterns of event reporting dependent on sponsor censoring dates, drug
      discontinuation and consent withdrawal in the PLATO trial. METHODS: Analysis of
      the Food and Drug Administration Complete Response Review for ticagrelor.
      RESULTS: Excluding adjudicated deaths, the distribution for clopidogrel appears
      more uniform while that for ticagrelor was skewed to the right, suggesting more
      events were reported after the sponsor censoring end date. PLATO investigators
      reported 16 unmatched primary endpoint events for ticagrelor immediately
      following the sponsor censoring date. Twenty-six out of 30 unreported events
      following early drug discontinuation occurred amongst patients using ticagrelor.
      More ticagrelor patients withdrew consent (Delta = 47), or were 'not willing' to
      complete the study (Delta = 87) when compared to clopidogrel. CONCLUSIONS: Site
      reported primary endpoints were unequally distributed for clopidogrel and
      ticagrelor in the PLATO trial. This pattern suggests the importance of
      questioning the impact of sponsor-mediated censoring on event reporting by
      investigators in indication-seeking trials. In PLATO, this pattern seems to have
      favored the experimental drug and may require further assessment.

PMID- 22418767
TI  - Is urinary incontinence a true consequence of deep brain stimulation of the
      pedunculopontine tegmental nucleus in Parkinson's disease?

PMID- 22418768
TI  - [Update on meat allergy. alpha-Gal: a new epitope, a new entity?].
AB  - The association between the carbohydrate galactose-[alpha]-1,3-galactose (alpha
      Gal) and anaphylaxis was first documented after severe hypersensitivity reactions
      to cetuximab, a chimeric mouse-human IgG1 monoclonal antibody approved for
      targeted therapy of carcinomas of colon, as well as of the head and neck region.
      alpha-Gal is a ubiquitous glycan moiety expressed on cells and tissue of non
      primate mammals. Since this epitope is not expressed in humans, it is very
      immunogenic for them.  alpha-Gal is located on the Fab portion of cetuximab and
      thus on the murine part of the chimera. The anaphylactic reactions to the
      antibody were mediated by IgE specific for alpha-Gal. Anti-alpha-Gal-IgE were
      first detected in sera of patients from the southeastern U.S. and reacted with a
      wide range of mammalian allergens. The geographic distribution prompted
      investigations of sensitization routes apart from the ingestion of red meat, such
      as tick bites und parasitic infections. Anti-alpha-Gal-IgE seems to be of
      clinical relevance for allergy to red meat and for the pork-cat syndrome. It is
      also associated with a novel form of delayed anaphylaxis, which appears more than
      3 hours following the ingestion of red meat (beef, pork and lamb), a phenomenon
      which is still to be elucidated. For most of these patients conventional skin
      prick tests with commercial reagents proved insufficient for diagnosis.

PMID- 22418769
TI  - [Severe toxic dermatitis after injection lipolysis].
AB  - The subcutaneous injection of phosphatidylcholine-containing substances is a
      frequently used method to reduce small localized fat deposits. Even though
      injection lipolysis is generally safe and free of complications, there have been
      rare reports on poor results, hematoma, infection or localized skin and tissue
      necrosis. A 28-year-old woman presented with an extensive toxic dermatitis
      characterized by well defined, erythematous, partly livid plaques as well as
      severe edema and strong pain about eighteen days after injection lipolysis on the
      thighs and knees.

PMID- 22418770
TI  - Synthesis, spectroscopic characterization, insulin-enhancment, and competitive
      DNA binding activity of a new Zn(II) complex with a vitamin B6 derivative--a new
      fluorescence probe for Zn(II).
AB  - This paper describes the activity of a Schiff base ligand, derived from
      pyridoxal, as a promising fluorescence probe for biologically important Zn(II)
      ion sensing. This is the first report of a vitamin based ligand as a fluorescent
      probe for sensing Zn(II) ions. The Schiff base H(2)pydmedpt, derived from the
      condensation of pyridoxal (pyd) and N,N-bis[3-aminopropyl]methylamine (medpt),
      exhibits around a 325-fold increase in fluorescence quantum yield due to zinc
      triggered fluorescence switching. The response is specific for Zn(II) ions, and
      remains unaffected by the presence of alkali and alkaline earth metals but is
      suppressed to varying degrees by transition metal ions. The corresponding Zn(II)
      complex, [Zn(pydmedpt], is isolated. The DFT optimized structure of the complex
      is compatible with elemental analysis, mass spectrometry, FT-IR, electronic and
      NMR spectra. The isolated complex, having pK(a) values of ~5.3 and ~5, is a
      moderate intercalator for DNA with an apparent binding constant of 2.3 * 10(6) M(
      1). The complex also shows insulin-enhancing activity at par with other reported
      complexes, with an IC(50) value of 0.65 with respect to ZnSO(4).

PMID- 22418771
TI  - Gall Bladder Metastasis from Breast Cancer Masquerading Symptomatic
      Cholelithiasis.

PMID- 22418772
TI  - Primary Epithelioid Amelanotic Malignant Melanoma of the Rectum: a Differential
      Diagnosis.

PMID- 22418773
TI  - A double-blind, randomized, multiple-dose, parallel-group study to characterize
      the occurrence of diarrhea following two different dosing regimens of neratinib,
      an irreversible pan-ErbB receptor tyrosine kinase inhibitor.
AB  - PURPOSE: Neratinib, a potent, low-molecular-weight, orally administered,
      irreversible, pan-ErbB receptor tyrosine kinase inhibitor has antitumor activity
      in ErbB2 + breast cancer. The objective of this study was to characterize the
      onset, severity, and duration of diarrhea after administration of neratinib 240
      mg once daily (QD) and 120 mg twice daily (BID) for <=14 days in healthy
      subjects. METHODS: A randomized, double-blind, parallel-group, inpatient study
      was conducted in 50 subjects given oral neratinib either 240 mg QD or 120 mg BID
      with food for <=14 days. The primary endpoint was the proportion of subjects with
      diarrhea of at least moderate severity (grade 2; 5-7 loose stools/day). In
      subjects with grade 2 diarrhea, fecal analytes were determined. Pharmacokinetic
      profiles were characterized for neratinib on Days 1 and 7. RESULTS: No severe
      (grade 3) diarrhea was reported. By Day 4, all subjects had grade 1 diarrhea.
      Grade 2 diarrhea occurred in 11/22 evaluable subjects (50 % [90 % confidence
      interval (CI): 28-72 %]) in the QD group and 17/23 evaluable subjects (74 % [90 %
      CI: 52-90 %]) in the BID group (P = 0.130). In fecal analyses, 18 % tested
      positive for hemoglobin and 46 % revealed fecal lactoferrin. Specimen pH was
      neutral to slightly alkaline. In pharmacokinetic analyses, Day 1 peak plasma
      concentration and Day 7 steady-state exposure were higher with the QD regimen
      than the BID regimen. In an exploratory analysis, ABCG2 genotype showed no
      correlation with severity or onset of diarrhea. CONCLUSIONS: Incidences and
      onsets of at least grade 1 and at least grade 2 diarrhea were not improved on BID
      dosing compared with QD dosing.

PMID- 22418775
TI  - Hydrocolloid-based nutraceutical delivery systems.
AB  - Nutraceuticals are important due to their inherent health benefits. However,
      utilization and consumption are limited by their poor water solubility and
      instability at normal processing and storage conditions. Herein, we propose an
      elegant and novel approach for the delivery of nutraceuticals in their active
      form using hydrocolloid matrices that are inexpensive and non-toxic with
      generally recognized as safe (GRAS) status. Iota-carrageenan and curcumin have
      been chosen as models of hydrocolloid and nutraceutical compounds, respectively.
      The iota-carrageenan network maintains a stable organization after encapsulating
      curcumin molecules, protects them from melting and then releases them in a
      sustained manner. These findings lay a strong foundation for developing value
      added functional and medicinal foods.

PMID- 22418776
TI  - Carbohydrates, glycemic index, glycemic load, and colorectal cancer risk: a
      systematic review and meta-analysis of cohort studies.
AB  - BACKGROUND: Dietary carbohydrate, glycemic index, and glycemic load are thought
      to influence colorectal cancer risk through hyperinsulinemia. We review and
      quantitatively summarize in a meta-analysis the evidence from prospective cohort
      studies. METHODS: We searched the PubMed database for prospective studies of
      carbohydrate, glycemic index, and glycemic load and colorectal cancer risk, up to
      October 2011. Summary relative risks were estimated by the use of a random
      effects model. RESULTS: We identified 14 cohort studies that could be included in
      the meta-analysis of carbohydrate, glycemic index, and glycemic load and
      colorectal cancer risk. The summary RR for high versus low intake was 1.00 (95%
      CI: 0.87-1.14, I2 = 31%) for carbohydrate, 1.07 (95% CI: 0.99-1.16, I2 = 28%) for
      glycemic index, and 1.00 (95% CI: 0.91-1.10, I2 = 39%) for glycemic load. In the
      dose-response analysis, the summary RR was 0.95 (95% CI: 0.84-1.07, I2 = 58%) per
      100 grams of carbohydrate per day, 1.07 (95% CI: 0.99-1.15, I2 = 39%) per 10
      glycemic index units, and 1.01 (95% CI: 0.95-1.08, I2 = 47%) per 50 glycemic load
      units. Exclusion of one or two outlying studies reduced the heterogeneity, but
      the results were similar. CONCLUSION: This meta-analysis of cohort studies does
      not support an independent association between diets high in carbohydrate,
      glycemic index, or glycemic load and colorectal cancer risk.

PMID- 22418778
TI  - Maternal and cord steroid sex hormones, angiogenic factors, and insulin-like
      growth factor axis in African-American preeclamptic and uncomplicated
      pregnancies.
AB  - BACKGROUND: A history of a preeclamptic pregnancy has been associated with
      subsequent increased risk of cardiovascular disease in the mother and decreased
      risk of breast cancer in both the mother and offspring. The concentrations of
      steroid sex hormones, angiogenic factors, and other proteins during pregnancy are
      important components of the in utero environment and may mediate the association
      of preeclampsia with later health outcomes. This study sought to compare an
      extensive profile of biological markers in both maternal and umbilical cord
      samples in preeclamptic and uncomplicated pregnancies of a predominantly African
      American population. METHODS: Steroid sex hormones, angiogenic factors, and
      components of the insulin-like growth factor axis were measured in maternal and
      umbilical cord sera from 48 pregnancies complicated by preeclampsia and 43
      uncomplicated pregnancies. Regression models estimated the associations of these
      markers with preeclampsia, after adjusting for maternal and gestational age.
      RESULTS: Concentrations of androgens (testosterone p = 0.06 and androstenedione p
      = 0.08) and the anti-angiogenic factors soluble fms-like kinase 1 (p = 0.004) and
      soluble endoglin (p = 0.004) were higher in the maternal circulation of women
      diagnosed with preeclampsia. These findings also were noted when the analyses
      were restricted to only African-American participants (77% of overall study
      population). Furthermore, among African-Americans, cord insulin-like growth
      factor-1 was lower in preeclamptic pregnancies than in controls. CONCLUSIONS: The
      associations of maternal androgens and anti-angiogenic factors with preeclampsia
      are consistent with prior reports from predominantly Caucasian populations.
      Alterations in these analytes as well as other maternal and fetal biomarkers in
      preeclampsia could mediate the associations of preeclampsia with later health
      consequences.

PMID- 22418777
TI  - Estrogen-related genes and their contribution to racial differences in breast
      cancer risk.
AB  - Racial differences in breast cancer risk, including the risks of hormone receptor
      subtypes of breast cancer, have been previously reported. We evaluated whether
      variation in genes related to estrogen metabolism (COMT, CYP1A1, CYP1B1, CYP17A1,
      CYP19A1, ESR1, GSTM1, GSTP1, GSTT1, HSD17B1, SULT1A1, and UGT1A1) contributes to
      breast cancer risk and/or racial differences in risk within the CARE study, a
      multi-centered, population-based case-control study of breast cancer. Genetic
      variation was assessed as single nucleotide polymorphisms (SNPs), haplotypes, and
      SNP-hormone therapy (HT) interactions within a subset of 1,644 cases and 1,451
      controls, including 949 Black women (493 cases and 456 controls), sampled from
      the CARE study population. No appreciable associations with breast cancer risk
      were detected for single SNPs or haplotypes in women overall. We detected SNP-HT
      interactions in women overall within CYP1B1 (rs1800440; p (het) = 0.003) and
      within CYP17A1 (rs743572; p (het) = 0.009) in which never users of HT were at a
      decreased risk of breast cancer, while ever users were at a non-significant
      increased risk. When investigated among racial groups, we detected evidence of an
      SNP-HT interaction with CYP1B1 in White women (p value = 0.02) and with CYP17A1
      in Black women (p value = 0.04). This analysis suggests that HT use may modify
      the effect of variation in estrogen-related genes on breast cancer risk, which
      may affect Black and White women to a different extent.

PMID- 22418779
TI  - Aviram-Ratner rectifying mechanism for DNA base-pair sequencing through graphene
      nanogaps.
AB  - We demonstrate that biological molecules such as Watson-Crick DNA base pairs can
      behave as biological Aviram-Ratner electrical rectifiers because of the spatial
      separation and weak hydrogen bonding between the nucleobases. We have performed a
      parallel computational implementation of the ab initio non-equilibrium Green's
      function (NEGF) theory to determine the electrical response of graphene--base
      pair--graphene junctions. The results show an asymmetric (rectifying) current
      voltage response for the cytosine-guanine base pair adsorbed on a graphene
      nanogap. In sharp contrast we find a symmetric response for the thymine-adenine
      case. We propose applying the asymmetry of the current-voltage response as a
      sensing criterion to the technological challenge of rapid DNA sequencing via
      graphene nanogaps.

PMID- 22418780
TI  - Intraocular activation of angiogenic and inflammatory pathways in uveal melanoma.
AB  - PURPOSE: To identify and quantify angiogenic and inflammatory cytokines in
      aqueous and vitreous humor in eyes with untreated uveal melanoma and to analyze
      clinicopathologic correlations. METHODS: Intraocular fluid samples of patients
      (uveal melanoma aqueous n = 21, vitreous n = 34) and controls (cataract aqueous n
      = 41, vitreomacular traction aqueous n = 35, vitreous n = 36) were taken
      intraoperatively and analyzed using Luminex xMAP suspension array technology.
      Beadlyte kits were used for detection of 28 different cytokines. RESULTS: Flt-3
      ligand, interleukin (IL) 1alpha, IL-6, IL-8, interferon-gamma inducible protein
      (IP)-10, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory
      protein 1alpha, platelet-derived growth factor AA, and vascular endothelial
      growth factor were significantly elevated in aqueous and vitreous of melanoma
      eyes when compared with controls. Eotaxin was significantly elevated in aqueous,
      and IL-7 and RANTES were significantly elevated in vitreous samples of melanoma
      eyes. Interferon-gamma inducible protein 10, macrophage inflammatory protein
      1alpha (aqueous and vitreous), Flt-3 ligand, IL-6, IL-8, and MCP-1 (vitreous)
      correlated with tumor dimensions. Further correlations were found between
      infiltration of Bruch membrane and Flt-3 ligand, MCP-1 (aqueous and vitreous), IL
      8, interferon-gamma inducible protein 10, macrophage inflammatory protein 1alpha,
      and platelet-derived growth factor AA (vitreous). Analyzing 16 paired aqueous and
      vitreous melanoma samples, Flt-3 ligand, IL-7, interferon-gamma inducible protein
      10, MCP-1, and platelet-derived growth factor AA were significantly elevated in
      vitreous, and IL-1alpha and vascular endothelial growth factor in aqueous
      samples. CONCLUSION: A range of significantly elevated angiogenic, inflammatory,
      and chemotactic cytokines in eyes with uveal melanoma supports the link between
      inflammation and tumorigenesis.

PMID- 22418781
TI  - Perceptual learning of auditory spectral modulation detection.
AB  - Normal sensory perception requires the ability to detect and identify patterns of
      activity distributed across the receptor surface. In the visual system, the
      ability to perceive these patterns across the retina improves with training. This
      learning differs in magnitude for different trained stimuli and does not
      generalize to untrained spatial frequencies or retinal locations. Here, we asked
      whether training to detect patterns of activity across the cochlea yields
      learning with similar characteristics. Differences in learning between the visual
      and auditory systems would be inconsistent with the suggestion that the ability
      to detect these patterns is limited by similar constraints in these two systems.
      We trained three groups of normal-hearing listeners to detect spectral envelopes
      with a sinusoidal shape (spectral modulation) at 0.5, 1, or 2 cycles/octave and
      compared the performance of each group to that of a separate group that received
      no training. On average, as the trained spectral modulation frequency increased,
      the magnitude of training-induced improvement and the time to reach asymptotic
      performance decreased, while the tendency for performance to worsen within a
      training session increased. The training-induced improvements did not generalize
      to untrained spectral modulation frequencies or untrained carrier spectra. Thus,
      for both visual-spatial and auditory spectral modulation detection, learning
      depended upon and was specific to analogous features of the trained stimulus.
      Such similarities in learning could arise if, as has been suggested, similar
      constraints limit the ability to detect patterns across the receptor surface
      between the auditory and visual systems.

PMID- 22418782
TI  - Abnormal capacity for grip force control in patients with congenital
      insensitivity to pain.
AB  - Congenital insensitivity to pain (CIP), which is an extremely rare sensory
      neuropathy, is defined as the absence of normal responses to noxious stimuli.
      Although motor function is not directly impaired in CIP patients, it is likely
      that the sensory deficit affects the motor control system. In order to
      characterize motor capacity in CIP patients, we here measured grip force and
      acceleration of a held object in 12 patients with CIP and 12 age-matched able
      bodied subjects. The results demonstrated that the grip force during the object
      grasp-lift-holding task was significantly greater, less reproducibility and
      greater fluctuation in the acceleration of the object in CIP patients than in
      normal subjects. Moreover, some patients showed absence of temporal coupling
      between the grip and load force, suggesting that anticipatory modulation of the
      grip force was at least partly impaired. As far as the authors know, this is the
      first study to characterize motor control ability in patients with CIP. The
      observed abnormal motor capacity can be at least partly attributed to a lack of
      sensory inputs mediated by Adelta and unmyelinated C-, specifically C-tactile,
      fibers. The present results may provide information useful for the prevention of
      secondary injury and education for patients during the developmental stage.

PMID- 22418785
TI  - Role of betasatellite in the pathogenesis of a bipartite begomovirus affecting
      tomato in India.
AB  - Betasatellites are commonly associated with tomato leaf curl disease caused by
      begomoviruses in India. This study demonstrates the role of a betasatellite in
      the pathogenesis of tomato leaf curl New Delhi virus (ToLCNDV), a bipartite
      begomovirus affecting tomato in India. For infection, accumulation, systemic
      movement and disease induction by ToLCNDV, co-infection by the associated
      betasatellite was not essential, as the DNA A alone of ToLCNDV could infect
      tomato and Nicotiana benthamiana and induce mild symptoms, but DNA B or Cotton
      leaf curl Multan betasatellite (CLCuMB) was required for development of typical
      leaf curl symptoms. The symptoms were most severe in plants infected with all
      three components, indicating a role of the betasatellite in the pathogenesis of
      ToLCNDV. The plants infected with ToLCNDV DNA A alone had limited accumulation of
      viral DNA, which increased by many times in plants co-infected with DNA B or/and
      betasatellite. However, the plants infected with all three components accumulated
      20 times less betasatellite DNA than the plants infected with DNA A and
      betasatellite. The increase in the amount of viral DNAs was also reflected in the
      commensurate increase in symptom severity and transmissibility by whitefly,
      Bemisia tabaci.

PMID- 22418783
TI  - The stability of M(max) and H (max) amplitude over time.
AB  - The stability of the maximal muscle response (M(max)) is critical to H reflex
      methodology. It has previously been reported that the amplitude of M(max)
      declines over time. If reproducible, this finding would have implications for all
      experimental studies that normalise the output of the motoneurone pool against
      the M wave. We investigated the effect of time on changes in M(max) and the
      maximal H reflex (H(max)) evoked at 4-s intervals over 60 min. To identify an
      influence of homosynaptic depression, we extended the interstimulus interval to
      10 s and the time to 100 min. Two recording montages over soleus were used to
      ensure that interelectrode distance was not a critical factor. The soleus M(max)
      and H reflex were evoked by stimulation of the tibial nerve in the popliteal
      fossa in 7 subjects who sat with the knee flexed to 30 degrees  and the ankle
      plantar flexed by ~30 degrees . We found no change in the pooled data for M(max),
      H(max), a reflex 50% of maximal, or the current required to produce it. However,
      one subject had a statistically significant increase in M(max) and a concurrent
      decrease in H(max) regardless of the interstimulus interval. On average, there
      was no change in the H(max)/M(max) ratio over time. While both M(max) and H(max)
      may change in response to many factors, these results suggest that, typically,
      time is not one of them.

PMID- 22418786
TI  - High pressure effect on phase transition behavior of lipid bilayers.
AB  - Phase behavior of lipid bilayers at high pressure is critical to biological
      processes. Using coarse grained molecular dynamic simulations, we report critical
      characteristics of dipalmitoylphosphatidylcholine bilayers with applied high
      pressure, and also show their phase transition by cooling bilayer patches. Our
      results indicate that the phase transition temperature of
      dipalmitoylphosphatidylcholine bilayers obviously shifts with pressure increasing
      in the rate of 37  degrees C kbar(-1), which are in agreement with experimental
      data. Moreover, the main phase transition is revealed to be strongly dependent on
      lipid area. A critical lipid area of ~0.57 nm(2) is found on the main phase
      transition boundary. Similar structures of acyl chains lead to the same
      sensitivity of phase transition temperature of different lipids to the pressure.
      Based on the lateral density and pressure profiles, we also discuss the different
      effects on bilayer structure induced by high temperature and high pressure, e.g.,
      increasing temperature induces higher degree of interdigitation of lipid tails
      and thinner bilayers, and increasing pressure maintains the degree of
      interdigitation and bilayer thickness.

PMID- 22418787
TI  - Does birth history account for educational differences in breast cancer
      mortality? A comparison of premenopausal and postmenopausal women in Belgium.
AB  - This study investigates the impact of reproductive factors on the association
      between education and breast cancer mortality in Belgium. The role of
      reproductive factors has been investigated in several studies, with mixed
      results. Reproductive factors are either completely or partially responsible for
      the association between education and breast cancer mortality. The data consist
      of the 1991 census linked to registration data on cause-specific mortality during
      the period 1991-1995, including all breast cancer deaths in Belgium during the
      observation period. The study population includes all women aged 35-79 at time of
      the census. Age-standardized mortality rates and mortality rate ratios (Poisson
      regression) are computed for educational groups with and without control for
      reproductive factors. The population is stratified according to age (women aged
      35-49 and 50-79) and according to nulliparity. The relationship between education
      and breast cancer is significant among postmenopausal women. Breast cancer
      mortality is higher among the higher educated women. These results are consistent
      with international findings, the gradient not being negative as in most other
      causes of death, but positive. Statistical control for parity and age at first
      birth reduces the association largely. In addition, among nonparous women,
      differences in breast cancer mortality by education are not consistent and
      generally not significant. Reproductive factors are largely responsible for the
      positive association between education and breast cancer mortality among
      postmenopausal women in Belgium. Among premenopausal women, the relation is not
      significant, a pattern consistent with international studies.

PMID- 22418788
TI  - Specific chemotaxis of magnetically labeled mesenchymal stem cells: implications
      for MRI of glioma.
AB  - PURPOSE: Glioblastoma multiforme (GBM) is a lethal disease marked by infiltration
      of cancerous cells into the surrounding normal brain. The dire outcome of GBM
      patients stems in part from the limitations of current neuroimaging methods.
      Notably, early cancer detection methodologies are lacking, without the ability to
      identify aggressive, metastatic tumor cells. We propose a novel approach for
      tumor detection using magnetic resonance imaging (MRI) based on imaging specific
      tumor tropism of mesenchymal stem cells (MSCs) labeled with micron-sized iron
      oxide particles (MPIOs). PROCEDURES: MPIO labeled and unlabeled MSCs were
      compared for viability, multi-lineage differentiation, and migration, where both
      chemotactic and chemokinetic movement were assessed in the presence of serum-free
      medium, serum-containing medium, and glioma-conditioned medium. MRI was performed
      on agarose samples, consisting of MPIO-labeled single MSCs, to confirm the
      capability to detect single cells. RESULTS: We determined that MPIO-labeled MSCs
      exhibit specific and significant chemotactic migration towards glioma-conditioned
      medium in vitro. Confocal fluorescence microscopy confirmed that MPIOs are
      internalized and do not impact important cell processes of MSCs. Lastly, MPIO
      labeled MSCs appear as single distinct, dark spots on T(2)*-weighted MRI,
      supporting the robustness of this contrast agent for cell tracking. CONCLUSIONS:
      This is the first study to show that MPIO-labeled MSCs exhibit specific tropism
      toward tumor-secreted factors in vitro. The potential for detecting single MPIO
      labeled MSCs provides rationale for in vivo extension of this methodology to
      visualize GBM in animal models.

PMID- 22418789
TI  - Curcumin has neuroprotection effect on homocysteine rat model of Parkinson.
AB  - Parkinson's disease (PD) is a progressive neurological disorder which is emanated
      by dopaminergic death cell and depletion. Curcumin as a nontoxic matter has
      antioxidant, anti-inflammatory, and antiproliferative activities, and it involves
      antioxidant property same to vitamins C and E. In this study, we investigated the
      neuroprotective properties of the natural polyphenolic antioxidant compound,
      curcumin, against homocysteine (Hcy) neurotoxicity. Curcumin (50 mg/kg) was
      injected intraperitoneally (i.p.) once daily for a period of 10 days beginning 5
      days prior to Hcy (2 MUmol/MUl) intracerebroventricular (i.c.v.) injection in
      rats. The studies included immunohistological and locomotor activity tests. These
      results suggest that homocysteine intracerebroventricular administration (2
      MUmol/MUl i.c.v.) may induce changes in rat brain, and subsequently, polyphenol
      treatment curcumin 50 mg/kg (i.p.) was capable in improving locomotor function in
      insulted animal by protecting the nervous system against homocysteine toxicity.

PMID- 22418791
TI  - [Moniter: debate on a press release].

PMID- 22418790
TI  - Protein kinase A-dependent substance P expression by pituitary adenylate cyclase
      activating polypeptide in rat sensory neuronal cell line ND7/23 cells.
AB  - The neurotrophic effects of pituitary adenylate cyclase-activating polypeptide
      (PACAP) on rat sensory neuronal cell line ND7/23 cells were investigated. PACAP
      caused a concentration-dependent increase in the number of neurite-bearing cells
      and the expression of the substance P precursor (PPT) mRNA in 24 h. The effects
      of PACAP were mimicked by vasoactive intestinal polypeptide with lower potency
      and dibutyryl-cyclic AMP, and inhibited by inhibitors of protein kinase A, ERK
      kinase or p38 kinase, KT5720, U0126, or SB203580, respectively. In a PPT promoter
      luciferase reporter assay, the increase of PPT mRNA was the result of an increase
      in PPT gene transcriptional activity by PACAP. The increasing effects of PACAP on
      PPT mRNA were similarly observed in primary cultured rat dorsal root ganglion
      cells. Thus, PACAP could induce differentiation-like phenomena in sensory neurons
      in a cAMP-, protein kinase A-, ERK kinase-, and p38 kinase-dependent manner.
      These results provide evidence of the neurotrophic action of PACAP, which may
      function to rescue damaged neurons or to switch the neuronal phenotype in injured
      or inflamed sensory neurons.

PMID- 22418792
TI  - [Alessandro Liberati: a personal appreciation].

PMID- 22418793
TI  - [Alessandro Liberati: a national and international reference point for
      epidemiology and health service research].

PMID- 22418794
TI  - [Energy, consumption, environment and health].

PMID- 22418795
TI  - [Fukushima, one year after].

PMID- 22418796
TI  - [Military condition and cancer].

PMID- 22418799
TI  - [Health impact assessment of pollution from incinerator in Modugno (Bari)].
AB  - OBJECTIVES: the purpose of this study is to assess the potential health impact of
      the start-up of a new incinerator in general population living near the facility
      in Modugno, province of Bari (Puglia Region, Italy), in combination with the
      existent Combined-Cycle combustion Gas Turbine (CCGT) power generation facility.
      DESIGN: an algorithm was used to calculate the number of cases (deaths and
      hospital admissions) associated with a given concentrations of PM10, the exposed
      population, the specific mortality/morbidity rate. For every health end-point, an
      estimate of RR was obtained from the literature. Using PM10 as tracer,
      simulations were made of incinerator emissions fallout. Residents within 2 km
      radius from the plants were considered. RESULTS: with the reduction of the
      average concentration of PM10 to 40 MUg/m(3), 0.12% of natural causes of death
      could be prevented. Proportionally, the increment in PM10 concentration of 1
      MUg/m(3) could be associated to 0.02% of deaths. CONCLUSIONS: the estimated
      health impact of the incinerator emissions doesn't modify the epidemiological
      profile for the population living nearby.

PMID- 22418798
TI  - [Environmental and health impacts of wood combustion to produce heat and power].
AB  - Toxic chemicals such as benzene, polycyclic aromatic hydrocarbons, dioxins, and
      ultra fine particles were found in the smoke produced by wood combustion.
      Emission factors confirm that, to produce the same energy amount, many more
      pollutants are emitted by wood than by natural gas. Biomass burning produces a
      relevant deterioration of air quality inside and outside houses, notably due to
      emissions of fine and ultra fine dust (PM10, PM2.5) according to reviewed
      studies. Important improvements in emission quality are obtained with the use of
      more efficient household heating systems, both in developed and in developing
      countries. Numerous studies have assessed the possible health effects produced by
      wood smoke, providing sufficient evidence that the indoor exposure to wood smoke,
      even in developed countries, can have adverse effects on human health. In 2010
      IARC classified wood smoke as a possible human carcinogen. In Europe, electricity
      generation from biomass combustion is increasing (12% each year) thanks to
      incentives provided to reduce greenhouse gas emissions and use of fossil
      fuels.Today adequate studies to assess the environmental and health effects of
      emissions from power plants fuelled by solid biomasses are still needed.

PMID- 22418800
TI  - [Use of seat belts and mobile phone while driving in Florence: trend from 2005 to
      2009].
AB  - OBJECTIVE: to evaluate the trend over time of the use of seat belts by drivers
      and passengers of cars and vans and the use of hand held mobile phone while
      driving in Florence from 2005 to 2009. DESIGN, SETTING AND PARTICIPANTS AND MAIN
      OUTCOME MEASURES: direct observations (58,773 vehicles) have been conducted to
      detect the use of seat belts by occupants of cars and vans, and the use of mobile
      phone while driving. It has been carried out correlation analysis between the use
      of the seat belt by occupants of vehicles and between the simultaneous use of
      this device and mobile phone while driving.Moreover, it has been carried out time
      series analysis (ARIMA Box Jenkins) of in the prevalence of the use of seat belts
      by occupants of vehicles observed, of mobile phone by drivers and the trend of
      the risk to drive using the mobile phone with unfastened seat belt rather than to
      drive using the mobile phone with fastened seat belt. RESULTS: seat belts were
      used on average by 75.7% of drivers, 75.5% of front passengers and 25.1% of rear
      passengers. The average mobile phone use while driving was 4.5%. Drivers most
      frequently fasten seat belt if front passengers use it and while they do not use
      mobile phone. The use of seat belts by drivers and front passengers has not
      changed over time, whereas the use of mobile phone while driving has
      significantly increased. The prevalence of using mobile phone with unfastened
      seat belt rather than to use it with fastened seat belt while driving has
      significantly decreased over the years, indicating an increase in the use of
      mobile phone, especially among those who fasten the seat belt. CONCLUSIONS: it is
      necessary to plan and realize stronger interventions in the whole area.

PMID- 22418801
TI  - [Lessons learned from the "Quirra syndrome" epidemiology? No, thanks].
AB  - Since January 2011, media reports have been reviving claims about a presumed
      excess of haemolymphopoietic cancer in south-eastern Sardinia, Italy, that
      started 10 years before.The almost daily sequence of articles created alarm in
      the local population, and a judicial investigation was initiated. The present
      commentary discusses possible reasons for the perception of an excess of
      haemolymphopoietic cancer, which was not confirmed by four independent
      epidemiological investigations. The update 2003 of the spatial analysis of
      haemolymphopoietic cancer incidence in southern Sardinia, on the other hand,
      commissioned by the local health authorities, has suggested an elevated risk of
      leukaemia among males residing in areas far from those reported at risk.No action
      followed. It is unclear why the regional authorities do not use the
      epidemiological investigations commissioned by themselves, whatever the results
      are either negative or positive for possible environmental health problems.

PMID- 22418802
TI  - [Lessons learned from the 'Quirra syndrome': more epidemiology and prevention].
AB  - The discussion here presented focuses on three issues included in the paper of P.
      Cocco: the perception of excesses of cancer mortality in selected areas of South
      East Sardinia, the report of excesses of cancer mortality in other areas of South
      Sardinia, the criticism towards public institutions for non-using scientific
      evidences. The starting point of the tale is the report done in 2001 by a General
      Practitioner about an excess of haemolymphopoietic cancers located in the Quirra
      suburb (Municipality of Villaputzu) and about an excess of congenital anomalies
      in the Municipality of Escalaplano. Cocco quotes four independent epidemiological
      studies excluding the existence of excesses of cancer mortality and incidence in
      the Salto di Quirra military area. Three questions are presented and discussed:
      why in this area, characterized by environmental pressures, where public anxiety
      and high risk perception have been report even before 2001, a specific
      surveillance program wasn't activated? why, after the reporting of congenital
      anomalies, there were neither epidemiological investigations nor a feasibility
      study about a registry? the ability of the four investigations quoted by Cocco
      was evaluated a priori? To discuss the conclusions of Cocco, some considerations
      concerning the methodological limits of the mentioned studies, the lack of micro
      geographical and etiological studies are suggested. The whole event indicates
      problems of communication, participation and relationships among stakeholders,
      and specifically the role of researchers when they have to face public
      administrators.

PMID- 22418803
TI  - [Epidemiological imaginary in Campania Region].
AB  - The interviews on the epidemiological imaginary, collected within the framework
      of the project Sebiorec,(1) clearly demonstrate that also in Campania, on the
      border between the provinces of Naples and Caserta - where the issue of waste and
      land devastation take forms that are unprecedented compared to any other part of
      Europe - there is a widespread, strong, sacrosanct demand of participation in
      environment and health management. The request of deliberative ecological
      democracy is pressing.(2) There is an urgent need to meet that plethora of rights
      emerging in the "knowledge society" and in the "risk society" that someone has
      called "rights for scientific citizenship."(3) This request of the population of
      Campania, net of local cultural specificity, it is quite similar to that of the
      people of any other region of Europe. The context in which this request of
      participation is expressed, however, is quite different. Not only and not just
      for that real or perceived social pre-modern and familist web that would replace
      a modern civil society in Campania and all across the Southern Italian regions,
      but also and especially for some structural causes that we here try to list.
      Campania is a unique region in Europe - in many ways different even from other
      regions of southern Italy - due to the conjunction of at least five factors, not
      independent from each other. 1) The presence of a widespread organized crime
      which, in many areas, metropolitan and non-metropolitan alike, and especially in
      the provinces of Naples and Caserta, is a sort of state against the State and has
      one of its main levers of power and a major source of its wealth in the illegal
      control of the territory, in its different dimensions (military, but also
      economic, social and even cultural). 2) A huge social and economic
      disintegration, exacerbated in the last twenty years by a process of
      deindustrialization (until the early nineties Naples was the fifth industrial
      city of Italy, today it is a desert where few productive oases survive) that has
      had few parallels in Europe and that, unlike other areas of the Old Continent,
      where the old manufacturing industries were closed, has not seen any serious plan
      to realize policy renewal and a reconstruction of its economy. 3) A huge
      population density, which makes at least part of the Campania region -
      particularly in the area straddling the provinces of Naples and Caserta - one
      single "in-finite" city, an "in-complete" megalopolis in which there is no
      solution of continuity between the rural and urban realities; in which cities,
      towns and countryside are piled up without order - without any order, because in
      the past, even in the recent past, that order somehow existed; houses,
      warehouses, roads and farmland, cement, fields, unauthorized dumping sites and
      again cement, in a state of chaos and, often, of deterioration that is, once
      again, almost unique in Europe. 4) The contemporary presence of two large
      migration flows, one incoming (usually non-EU), the other outgoing (with a very
      high number of migrant graduates), are interwoven in a way chaotic to further
      contributing to tear the already tattered social fabric. 5) Last but not least,
      the authoritative answer of the State that, in its various forms, now explicitly
      (through laws and decrees) now implicitly (through activities or omissions of
      bureaucracies) effectively inhibits at all levels the demand of participation, of
      transparency and even of simple information. The authoritarianism of the State
      and its bureaucracies was recently only scratched by the evolution of the local
      and national political events.

PMID- 22418805
TI  - [Causality, didactics and climate change].

PMID- 22418806
TI  - [Beyond genetics].

PMID- 22418804
TI  - [Counseling on life style delivered during cancer secondary prevention practice:
      considerations after the SPRINT study experience in Florence, Mantua and Turin].
AB  - In the short paper we report the results of a workshop on the feasibility to
      carried out a brief counselling on smoking cessation and physical activity to
      female smokers attending the Italian National Health System Cervical Cancer
      Screening Program. The considerations derived from the midwives' experience
      during the recruitment of women for the SPRINT study, an intervention trial
      designed in order to verify the effectiveness of a standard counselling
      intervention on smoking cessation delivered by trained midwives in a gender
      specific setting, the outpatient cervical cancer screening visits.

PMID- 22418807
TI  - [Mobile phones, uncertainty and precaution].

PMID- 22418808
TI  - [Less than one third of people with chronic medical conditions have the flu
      vaccination].

PMID- 22418809
TI  - Safety assessment and immunogenicity of a cell-culture-derived influenza vaccine
      in adults and elderly subjects over three successive influenza seasons.
AB  - BACKGROUND: Adult and elderly subjects previously immunized with cell culture
      derived (CCIV; Optaflu((r))) or egg-derived (TIV; Agrippal((r))) trivalent
      influenza vaccines were enrolled in two extension studies (E1 and E2) to evaluate
      safety and immunogenicity after revaccination with CCIV/TIV alone or in
      combination with concomitant pneumococcal vaccine (PV). METHODS: Adults and
      elderly subjects (n = 2609) were randomized 1:1 in E1 and allocated 3:1 in E2 to
      receive CCIV/TIV. In E2, a subset of elderly subjects was randomized to receive
      CCIV/TIV, with or without PV. Adverse reactions were monitored for six months and
      immunogenicity was assessed by hemagglutination inhibition (HI) assay using CHMP
      criteria. RESULTS: Overall, the safety profile of both vaccines was similar, no
      serious adverse events related to either vaccine occurred. Mild or moderate pain
      was the most commonly reported reaction. Reactogenicity was slightly higher in
      elderly subjects receiving CCIV/TIV concomitantly with PV [46% vs. 37%; p = non
      significant (NS)]. Both vaccines met CHMP licensure criteria for adults and
      elderly subjects. With concomitant CCIV and PV, all three CHMP criteria were met
      for A/H1N1 and A/H3N2, whereas the B strain only met seroprotection and GMR
      criteria. CONCLUSIONS: Safety and immunogenicity of CCIV was not influenced by
      the type of vaccine received previously or by concomitant PV administration.

PMID- 22418810
TI  - Management of the lower third of the face and neck.

PMID- 22418811
TI  - Lower branches of the facial nerve.
AB  - Various aesthetic procedures have been developed over the past several decades
      for facial rejuvenation. One of the parallel goals is protection of vital
      structures such as the facial nerve. In this study, 10 cadaveric hemifacial
      dissections were performed, and the course of the lower portion of the facial
      nerve was studied with specific attention addressed toward the three-dimensional
      location of the nerve as it relates to the usual superficial tissue planes that
      are dissected during the course of an open facial rejuvenation procedure. The
      locations of the nerve as it runs within the different planes in addition to some
      suggestions to avoid injury to the lower branches of the facial nerve are
      discussed.

PMID- 22418812
TI  - Injectable fillers for volume replacement in the aging face.
AB  - In recent years, there has been a better understanding of the aging process. In
      addition to changes occurring in the skin envelope, significant changes occur in
      the subcutaneous fat and craniofacial skeleton. This has led to a paradigm shift
      in the therapeutic approach to facial rejuvenation. Along with soft tissue
      repositioning, volumizing the aging face has been found to optimize the result
      and achieve a more natural appearance. Early in the aging process, when there has
      not been a significant change to the face requiring surgical intervention,
      fillers alone can provide minimally invasive facial rejuvenation through
      volumizing. Multiple injectable soft tissue fillers and biostimulators are
      currently available to provide facial volume such as hyaluronic acid, calcium
      hydroxylapatite, poly-L-lactic acid, polymethyl methacrylate, and silicone. A
      discussion of the morphological changes seen in the aging face, the properties of
      these products, and key technical concepts will be highlighted to permit optimum
      results when performing facial volumizing of the upper, middle, and lower thirds
      of the face. These fillers can act as a dress rehearsal for these patients
      considering structural fat grafting.

PMID- 22418813
TI  - Autologous fat grafting to the lower one-third of the face.
AB  - Volume loss contributes as much to the aging appearance of the face as sagging
      and rhytids. This occurs in the nasolabial and labiomental creases, as well as
      the lips, mandibular ramus, and the prejowl sulcus. Treatment of these areas with
      autogenous fat has yielded results that are generally good, but often of brief
      duration. To obtain the best results, trauma to the transplanted adipocytes must
      be avoided through meticulous attention to the details of technique. Observed
      complications are usually minor. Despite variability in the duration of effect,
      the fact that autogenous fat is relatively inexpensive and readily available
      makes it a viable alternative for facial volume replacement.

PMID- 22418814
TI  - Surgery of the chin.
AB  - With a clear understanding of the anatomy and thorough patient evaluation, a safe
      and effective surgical plan can be constructed. There are several options
      available to reduce or augment the chin, and often the choice is based on patient
      presentation and surgeon comfort and familiarity with a given procedure.

PMID- 22418815
TI  - Neck rejuvenation--anatomy and clinical correlation.
AB  - The restoration of the aesthetic contour of the neck is a challenging but
      important component of facial rejuvenation. Numerous techniques have been
      developed to improve the aesthetic outcome. We plan to give an overview of
      anatomic principles and their clinical correlation.

PMID- 22418816
TI  - Direct cervicoplasty.
AB  - The sagging neck, or "turkey gobbler" deformity, is one of the more common
      reasons that patients present to facial plastic surgeons. Although many of these
      patients might be best improved by a full rhytidectomy with periauricular
      incisions, skin flap undermining, and platysmal tightening, there are some
      patients who do not wish to undergo a full rhytidectomy. Some of these patients
      may be reasonably well served by a direct cervicoplasty or submentoplasty. The
      advantages of this approach include shorter operative time, faster recovery, and
      lower complication rates. The primary disadvantage is an anterior cervical
      incision that may be visible under some conditions. This article will review the
      options for skin incisions as well as technical details that may lead to a
      successful rejuvenation of the submental region.

PMID- 22418817
TI  - Managing the neck in the era of the short scar face-lift.
AB  - A recent trend in rhytidectomy has included the introduction of various short
      incision techniques, particularly the S-lift, the minimal access cranial
      suspension lift, and other short scar methods. However, this trend has not been
      without a criticism that these minimally invasive techniques might be limited in
      what might be achievable by such surgery. As with more traditional face-lift
      surgery, the management of the neck often presents as the most challenging aspect
      of the procedure when using short scar techniques. This article will present a
      brief history of cervical rhytidectomy and relevant surgical anatomy, as well as
      the authors' algorithmic approach to surgical assessment and management of the
      neck, the short incision operative techniques, and potential complications. In
      the authors' experience, attention to both the selection criteria and operative
      modifications in the execution of short scar techniques are critical to
      optimizing outcomes in cervical rejuvenation.

PMID- 22418818
TI  - Minimal incision face-lifting.
AB  - Rhytidectomy has been performed for over 100 years, but only more recently has it
      become generally accepted by society. Recent improvements in access to
      information has produced more public awareness of the possible aesthetic
      enhancements. Additionally, there has been a trend for the younger patient to
      seek cosmetic surgery, often requesting procedures with minimal incisions and
      less downtime. The mini-lift, with its decreased operating time and expense,
      rapid recovery, as well as more limited incisions and tissue elevation, is an
      ideal procedure for patients with a smaller degree of cheek and neck laxity. We
      describe our concept of the mini-lift and address what results can be expected.

PMID- 22418819
TI  - Lower face-lift with extensive neck recontouring.
AB  - Difficult anatomy and advanced aging continue to pose a challenge to the face
      lift surgeon. We present a thorough analysis of the patient with respect to
      relevant vascular anatomy, as well as our techniques used to address advanced
      cases, including compartment communication and submental suspension
      platysmaplasty.

PMID- 22418820
TI  - The McCollough Facial Rejuvenation System: expanding the scope of a condition
      specific algorithm.
AB  - The ideal facial rejuvenation algorithm is comprised of an appropriate
      combination of procedures, thoughtfully chosen from an assortment of reliable
      alternatives, that when skillfully performed provide both short- and long-term
      enhancement to the undesirable conditions of aging that exists at the time of
      treatment. In 2010, the senior author published the first scientific article in
      which a condition-specific classification system and a treatment plan algorithm
      were applied to the discipline of facial rejuvenation. In the landmark article,
      the senior author reviewed his surgical experience of more than 5000 face-lifts
      and grouped patients into five major categories (or stages), based upon the
      extent of aging identified in various regions of the face and neck and the
      procedures performed to correct them. The criteria (that have now been suggested
      on a facial aging worksheet) were recorded in a data blank comprised of a first
      generation worksheet. Once the data were collected--and using algorithmic charts
      for each region and/or facial feature--the most appropriate plan of action for a
      given patient was created. The sole objective in sharing the senior author's
      methodology was to launch a scholarly discussion among physicians and surgeons
      involved in the various disciplines that provide rejuvenation procedures on the
      face, head, and neck. From such a debate would, hopefully, emerge a definitive
      algorithmic system--one based squarely on the venerable ethics of medicine,
      coupled with the appropriate application of and skillful performance of the
      fundamental principles of surgery. A single, science-based system would restore
      order to a noble discipline, currently being challenged by narcissism, gimmickry,
      and commercialization. The implementation of a system rooted in universal truths
      would require its advocates to agree upon a common "language," the implementation
      of which allows aesthetically focused surgeons to share both new ideas and time
      tested experiences. More importantly, a condition-specific system matches each
      potential patient's problems--at every age--with the appropriate facial
      rejuvenation treatment plan, restoring the ideals of science and art to the
      profession. Initially provided in a consumer information book devised to assist
      patients with understanding the advantages of personalized treatment plans, the
      senior author later shared his practices and evolving system with colleagues
      attending conventions, seminars, and courses. Only after he was convinced that
      his system could be of benefit to physicians and surgeons from a variety of
      backgrounds was it offered to the peer-reviewed medical literature. Clearly, a
      plethora of techniques and materials are available for facial rejuvenation;
      however, only the ones deemed to be worthy of consideration were included. In
      practice--and in this presentation--the authors expanded the scope of the
      previously published article and offer a user-friendly, condition-specific
      worksheet and algorithmic tables designed to make it easier for surgeons to
      select the right combinations of procedures--at the right time in a patient's
      life. Although imitations potentiate an environment of disharmony, the authors
      remain committed to enabling the evolution of a single facial rejuvenation
      classification system, one that--with the input of like-minded scholars--could
      restore needed order to a branch of the medical profession that, in recent years,
      seems to have lost its focus.

PMID- 22418821
TI  - Chemical face peeling.
AB  - Chemexfoliation is an excellent method to reduce facial rhytids. For 25 years, we
      have used the traditional formula as described by T. J. Baker but with a moist
      healing technique rather than a tape mask. We have found the peel to be
      inexpensive and easy to perform, with results that are excellent and consistent,
      with minimal side effects.

PMID- 22418822
TI  - The web lift and posterior pull for the aging face.
AB  - There are many factors that contribute to the aging neck. We have recently begun
      employing a percutaneous suture spanning the submentum combined with a posterior
      platysma pull. We present our initial results with this technique. In this
      retrospective study, subjects underwent the combined procedure with and without
      concomitant rhytidectomy. Cephalometric analysis was used to compare the
      preoperative cervicomental angle (CMA) and hyomental distance (HMD) with
      postoperative values at 4 weeks. Subjects also were queried on their
      postoperative satisfaction. Twenty-five subjects were included in this study. At
      4 weeks postoperatively, we achieved significant reductions in the average CMA
      (134.8 versus 122.8, p = 0.002). The postoperative HMD significant increased an
      average of 1.9 cm (8.5 versus 10.4, p = 0.009). We achieved a 92.3% satisfaction
      score at 33 weeks (range = 25 to 44). The combination of a percutaneous suture
      across the submentum and a posterior platysma pull is a safe and effective method
      of addressing the many facets of the aging neck. Our initial results are easily
      reproducible and entail minimal morbidity to the patient.

PMID- 22418823
TI  - Scrotal cancer survival is influenced by histology: a SEER study.
AB  - INTRODUCTION: Due to the scrotum's multiple layers of different tissues, scrotal
      cancer can present with several unique histologies. Historically, outcome arising
      from these different sources has been historically aggregated together. However,
      it remains unclear whether survival differs by histology of scrotal cancer.
      METHODS: We queried the seventeen registries of the Surveillance, Epidemiology,
      and End Results database for patients diagnosed with primary scrotal cancer from
      1973 to 2006. Patients were initially grouped by the following histologies: basal
      cell carcinoma, Extramammary Paget's Disease (EMPD), sarcoma, melanoma, squamous
      cell carcinoma, and adnexal skin tumors. For some analyses, the former three
      histologies were reclassified as Low-Risk scrotal cancer and the latter three
      histologies as High-Risk scrotal cancer. Kaplan-Meier survival analyses were
      conducted to assess the impact of histology on overall survival (OS). RESULTS:
      The cohort consisted of 766 patients. Median (95% CI) OSs by histologies were
      basal cell carcinoma--143 (116-180), EMPD--165 (139-190), sarcoma--180 (141-219),
      melanoma--136 (70-203), squamous cell carcinoma--115 (97-133), and adnexal skin
      tumors--114 (55-174). Patients with Low-Risk scrotal cancer experienced a median
      (95% CI) OS of 166 (145-188) months, while patients with High-Risk scrotal cancer
      experienced a median (95% CI) OS of 118 (101-135) months. CONCLUSIONS: Survival
      of scrotal cancer depends on tumor histology. Classification of histologies into
      Low and High Risk can be clinically useful for counseling and clinical decisions.

PMID- 22418824
TI  - Effect of the attachment of ferromagnetic contacts on the conductivity and giant
      magnetoresistance of graphene nanoribbons.
AB  - Carbon-based nanostructures and graphene, in particular, evoke a lot of interest
      as new promising materials for nanoelectronics and spintronics.  One of the most
      important issues in this context is the impact of external electrodes on the
      electronic properties of graphene nanoribbons (GNRs). The present theoretical
      method is based on the tight-binding model and a modified recursive procedure for
      Green's functions. The results show that within the ballistic transport regime,
      the so-called end-contacted geometry (of minimal GNR/electrode interface area),
      is usually more advantageous for practical applications than its side-contacted
      counterpart (with a larger coverage area), as far as the electrical conductivity
      is concerned. As regards the giant magnetoresistance coefficient, however, the
      situation is exactly the opposite, since spin-splitting effects are more
      pronounced in the lower conductive side-contacted setups.

PMID- 22418825
TI  - [Rescue time and survival of severely injured patients in Germany].
AB  - BACKGROUND: Independent of the rescue system type, a rescue time of less than 60
      min for trauma patients is usually required and considered to be crucial for the
      outcome. The goal of this study was to investigate the impact of the rescue time
      on hospital survival in severely injured patients. METHODS: With the help of the
      German Trauma Registry of the DGU, the population and rescue time were
      systematically analyzed with regard to the survival rate. A lower mortality rate
      was observed with a higher injury severity in metropolitan cities compared to
      small towns. RESULTS: A multivariate regression analysis revealed no clinically
      relevant impact of the rescue time length in the German rescue system on
      survival. This can be explained by a higher amount of preclinical medical
      procedures during longer rescue times. CONCLUSIONS: Within the German rescue
      system, the length of rescue time has no relevant impact on the survival of
      trauma patients admitted to a clinic. This could be explained by the higher
      numbers of preclinical measures and due to the limitations of a register study
      with selection bias. Therefore, we advocate that the necessary and suitable
      preclinical medical procedures be performed to stabilize the patient, even in
      cases that have exceeded the 60-min gold standard time window. In conclusion the
      "golden hour" concept today might better be interpreted as an individual and
      appropriate "golden period" of trauma.

PMID- 22418826
TI  - Glycation of plasma proteins in type II diabetes lowers the non-covalent
      interaction affinities for dietary polyphenols.
AB  - Diabetes is characterized by an elevated level of glucose in the blood. This
      glucose can form covalent adducts with plasma proteins through a non-enzymatic
      process known as glycation. It has been suggested that the increasing glycation
      can influence the ability of plasma proteins to bind to small molecules. Herein,
      the difference between healthy human plasma proteins (HPP) and type II diabetes
      plasma proteins (TPP) in binding small molecules was investigated. TPP showed
      about 1-10 times lower affinities for polyphenols than HPP. The values of lg
      K(a)(HPP) are positive proportional to the values of lg K(a)(TPP) with excellent
      linear relationship. The glycation of HPP decreased the affinities for HPP by
      about 1.17 to 16.6 times. The difference between HPP-polyphenol interaction and
      TPP-polyphenol interaction was bigger for the more lipophilic polyphenols. The
      affinities for TPP or HPP slightly decreased with increasing hydrogen bond donor
      numbers of polyphenols and hardly changed with hydrogen bond acceptor numbers.

PMID- 22418827
TI  - Effect of heat shock on ultrastructure and calcium distribution in Lavandula
      pinnata L. glandular trichomes.
AB  - The effects of heat shock (HS) on the ultrastructure and calcium distribution of
      Lavandula pinnata secretory trichomes are examined using transmission electron
      microscopy and potassium antimonate precipitation. After 48-h HS at 40 degrees C,
      plastids become distorted and lack stroma and osmiophilic deposits, the cristae
      of the mitochondria become indistinct, the endoplasmic reticulum acquires a chain
      like appearance with ribosomes prominently attached to the lamellae, and the
      plasma and organelle membranes become distorted. Heat shock is associated with a
      decrease in calcium precipitates in the trichomes, while the number of
      precipitates increases in the mesophyll cells. Prolonged exposure to elevated
      calcium levels may be toxic to the mesophyll cells, while the lack of calcium in
      the glands cell may deprive them of the normal protective advantages of elevated
      calcium levels. The inequality in calcium distribution may result not only from
      uptake from the transpiration stream, but also from redistribution of calcium
      from the trichomes to the mesophyll cells.

PMID- 22418828
TI  - CYP2C19 polymorphism affects single-dose pharmacokinetics of oral pantoprazole in
      healthy volunteers.
AB  - OBJECTIVES: Pantoprazole is metabolized by cytochrome P450 2 C19, which shows
      genetic polymorphism. The effect of CYP2C19 polymorphism on single-dose
      pharmacokinetics of oral pantoprazole in healthy volunteers was evaluated.
      METHODS: Pantoprazole pharmacokinetics was determined in 32 healthy volunteers
      after a 40-mg single oral dose of the drug. RESULTS: Carriers of CYP2C19*2/*2 (n
      = 2) were characterized by higher, starting from 3.5 h post dose, plasma
      concentrations of pantoprazole in comparison to wild-type (CYP2C19*1/*1, n = 6)
      volunteers. In subjects with CYP2C19*17/*17 genotype (n = 6) significantly lower
      plasma concentrations of the drug vs CYP2C19*1/*1 carriers, were observed from
      3.0 h after oral pantoprazole administration. Carriers of CYP2C19*1/*17 (n = 6)
      and CYP2C19*2/*17 (n = 6) displayed concentration-time profiles comparable to
      wild-type subjects. CYP2C19*2/*2 volunteers showed a decrease in terminal
      elimination rate constant (lambda(z)) by 83.3%, prolongation of terminal half
      life (t(1/2)) by 572%, a rise in area under the concentration-time curve (AUC)
      and mean residence time (MRT) by 506% and 259% respectively. Heterozygotes, i.e..
      CYP2C19*1/*2 vs CYP2C19*1/*1 were characterized by higher AUC (4.38 +/- 1.00
      mg.h/L vs 3.00 +/- 1.02 mg.h/L, p < 0.05) and C(max) (2.13 +/- 0.42 mg/L vs 1.61
      +/- 0.35 mg/L, p < 0.05) respectively. A significant reduction in MRT (3.83 +/-
      0.82 h vs 2.73 +/- 0.23 h, p < 0.05) in carriers of CYP2C19*17/*17 vs
      CYP2C19*1/*1 genotypes was observed. Population modeling confirmed the influence
      of *1/*2, *2/*2, and *17/*17 genotypes on the pharmacokinetics of pantoprazole.
      The lowest population oral clearance was assessed in the carriers of genotype
      *2/*2 (3.68 L/h) and the highest value in subjects with genotype *17/*17 (31.13
      L/h). CONCLUSION: These data suggest that CYP2C19 polymorphism is an important
      determinant of pantoprazole pharmacokinetics.

PMID- 22418829
TI  - Entry-into-humans study with a new direct renin inhibitor.
AB  - PURPOSE: To evaluate the pharmacokinetics, pharmacodynamics, safety, and
      tolerability of escalating single oral doses of ACT-077825, a novel orally active
      renin inhibitor, in healthy male subjects. METHODS: In this single-center, double
      blind, placebo- and active-controlled (with enalapril) randomized study, 70
      subjects received a single dose of ACT-077825 (1-1,000 mg), placebo, or enalapril
      20 mg under fasted conditions. The main pharmacokinetic endpoints were area under
      the plasma ACT-077825 concentration-time curve from time zero to infinity and the
      terminal half-life (t(1/2)). The pharmacodynamic endpoints included immunoactive
      active renin (iAR) plasma concentrations and plasma renin activity (PRA).
      Standard laboratory and safety data were collected. RESULTS: Of the few adverse
      events reported, diarrhea and headache were the most frequent. The
      pharmacokinetics of ACT-077825 were dose-proportional in the dose range 100 to
      1,000 mg. Terminal t(1/2), best characterized following a dose of 1,000 mg, was
      41.6 h and t(max) 4-5 h post-dose. ACT-077825 dose-dependently increased iAR and
      decreased PRA, effects that were associated with a decrease in blood pressure at
      1,000 mg, similar to following treatment with enalapril. CONCLUSION: The results
      provide evidence that ACT-077825, with a pharmacokinetic profile consistent with
      a once-a-day dosing regimen, may represent an effective antihypertensive agent
      and pave the way toward a multiple-ascending dose study.

PMID- 22418830
TI  - Healthcare providers' experiences with adverse drug reactions and adherence
      challenges in antiretroviral therapy of HIV patients in the Eastern Cape
      Province, South Africa.
AB  - PURPOSE: To gain insight into the experiences and handling of adverse drug
      reactions (ADRs) by the staffs of public primary healthcare (PHC) clinics in
      Eastern Cape Province, South Africa, as well as their perceptions of related
      adherence challenges in the treatment and follow-up of human immunodeficiency
      virus (HIV)-positive patients. METHODS: Healthcare providers working at the PHC
      level in the public sector in the study area were approached and asked to
      participate in focus group discussions (FGDs). Seven FGDs were conducted with 32
      healthcare providers (9 nurses, 23 auxiliary staff). Questions introduced by the
      moderator of each FGD were freely discussed by the participants. Discussions were
      audio-recorded and subjected to thematic content analysis. RESULTS: Several
      challenges in the treatment and follow-up of patients on ART were identified.
      These include: (1) lack of training of healthcare providers in PHC clinics to
      confidently identify, manage and treat the ADRs HIV-positive patients receiving
      ART; (2) patients' difficulty in communicating information on ADRS; (3)
      insufficient pharmacovigilance; (4) role of poverty. CONCLUSION: Both nurses and
      auxiliary staff expressed lack of knowledge and confidence regarding ADRs in HIV
      patients and management of this. More emphasis is warranted on training the
      healthcare providers to identify ADRs and provide adequate advice for continued
      treatment of patients experiencing potential drug related problems.

PMID- 22418832
TI  - Re: Farjoodi P, Skolasky RL, Riley LH. The effects of hospital and surgeon volume
      on postoperative complications after lumbar spine surgery. Spine 2011;36:2069
      2075.

PMID- 22418831
TI  - Itraconazole and domperidone: a placebo-controlled drug interaction study.
AB  - PURPOSE: To determine the influence of itraconazole on the pharmacokinetics, and
      the CNS and prolactin-elevating effects of domperidone in humans. METHODS:
      Fifteen healthy volunteers received either itraconazole (200 mg daily) or placebo
      for 5 days with a double blind, randomized, cross-over design. A single oral 20
      mg dose of domperidone was administered to subjects on day 5. Plasma domperidone
      and serum prolactin concentrations were measured. The effects of domperidone on
      CNS were also assessed using self-rating scales and electroencephalography.
      RESULTS: Itraconazole significantly increased domperidone AUC(0-infinity) (3.2
      fold) and C(max) (2.7-fold) compared with placebo, but had no significant effect
      on the elimination half-life of domperidone. The CNS effects of domperidone
      assessed by self-rating of mood and electroencephalography, and the prolactin
      elevating effect, were not significantly affected by itraconazole. A
      counterclockwise hysteresis was evident in the relationship between plasma
      domperidone and serum prolactin concentrations. Itraconazole shifted the
      hysteresis to the right. Concentration-effect modeling procedures yielded a
      significant linear relationship between hypothetical effect site domperidone
      concentrations and prolactin levels. Itraconazole reduced the slope of the linear
      relationship. CONCLUSIONS: Itraconazole significantly increased plasma
      domperidone concentrations. The interaction is probably mainly due to a reduced
      first pass elimination by inhibition of CYP3A and/or MDR1. The clinical
      significance of the altered relationship between domperidone concentrations and
      prolactin levels caused by itraconazole is still to be determined.

PMID- 22418835
TI  - Translation initiation in colorectal cancer.
AB  - Colorectal cancers (CRC) are one of the most common causes of morbidity and
      mortality in high-income countries. Targeted screening programs have resulted in
      early treatment and a substantial decrease in mortality. However, treatment
      strategies for CRC still require improvement. Understanding the etiology and
      pathogenesis of CRC would provide tools for improving treatment of patients with
      this disease. It is only recently that deregulation of the protein synthesis
      apparatus has begun to gain attention as a major player in cancer development and
      progression. Among the numerous steps of protein synthesis, deregulation of the
      process of translation initiation appears to play a key role in cancer growth and
      proliferation. This manuscript discusses a fascinating and rapidly growing field
      exploring translation initiation as a fundamental component in CRC development
      and progression and summarizing CRC treatment perspectives based on agents
      targeting translation initiation.

PMID- 22418836
TI  - Postgraduate training in anaesthesiology, pain and intensive care:  the new
      European competence-based guidelines.

PMID- 22418837
TI  - Spinal haematoma after epidural puncture.

PMID- 22418839
TI  - Crystal structure of Human ASB9-2 and substrate-recognition of CKB.
AB  - Human ankyrin repeat and suppressor of cytokine signaling box protein 9 (hASB9)
      is a specific substrate-recognition subunit of an elongin C-cullin-SOCS box E3
      ubiquitin ligase complex. It recognizes its substrate, brain type creatine kinase
      (CKB), using the ankyrin repeat domain; and facilitates the polyubiquitination of
      CKB to mediate proteasomal degradation through the SOCS box domain. HASB9-2 is an
      isoform of hASB9 that contains one ankyrin repeat domain. In this study, the
      crystal structure of hASB9-2 is shown at 2.2-A resolution using molecular
      replacement. Overall, hASB9-2 forms a slightly curved arch with a characteristic
      L-shaped cross-section. Amino acid substitution analysis based on docking
      experiments revealed that His103 and Phe107 in hASB9-2 are essential for binding
      to CKB. Analysis of truncation mutants demonstrated that the first six ankyrin
      repeats along with the N-terminal region of hASB9-2 contribute to the interaction
      with CKB.

PMID- 22418840
TI  - Might psoriasis be a risk factor for obstructive sleep apnea syndrome?
AB  - BACKGROUND: It is believed that psoriasis is a chronic systemic inflammatory
      disease. Obstructive sleep apnea syndrome (OSAS) is a disease influencing all
      systems and characterized by intermittent partial or complete obstruction of the
      upper respiratory tract during sleep. In our study, we aimed to investigate the
      frequency of OSAS in patients previously diagnosed with psoriasis in order to
      investigate a potential association between chronic inflammation psoriasis and
      OSAS. METHODS: Thirty-three patients diagnosed with psoriasis by biopsy were
      enrolled into the study. Demographics of patients, Psoriasis Area Severity Index
      (PASI), Dermatology Life Quality Index (DLQI), and Epworth Sleepiness Scale were
      examined. All patients underwent polysomnography. RESULTS: OSAS was determined in
      18 of 33 patients with psoriasis (54.5 %). Eleven of the 18 patients had mild, 2
      had moderate, and 5 had severe OSAS. Mean age was significantly higher in the
      OSAS group in comparison with non-OSAS group (54.4 +/- 15.5 vs 39.4 +/- 11.8,
      respectively, p < 0.05). Mean PASI was higher in the OSAS group in comparison
      with that of non-OSAS group, and the difference was not significant, although
      mean DLQI was lower (p > 0.05). It is believed that this was caused by the small
      patient population. CONCLUSION: We detected that the frequency of OSAS in
      patients with psoriasis was much higher than that in the normal population.
      Though OSAS is not easy to diagnose without detailed testing, it should be
      investigated in psoriatic patients with long disease duration and high PASI
      score, and patients refractory to conventional systemic treatment. Physicians
      treating patients with psoriatic disease should incorporate this life-altering
      comorbidity into their assessment of disease and selection of treatment.

PMID- 22418841
TI  - [Methods to increase participation in cancer screening programmes].
AB  - OBJECTIVE: to synthesize scientific evidences about methods to increase cervical,
      breast and colorectal cancer screening participation. METHODS: a
      multidisciplinary working group has been set up to define the scope of the report
      and to conduct the evaluation. The scope and the final evaluation have been
      submitted to a stakeholder committee, including the Ministry of Health, the
      National Screening Observatory, regional screening program coordinators,
      scientific societies, and Lega Italiana Lotta ai Tumori, for comments and
      integrations. A systematic review of the principal biomedical and social
      literature databases was conducted to identify experimental and observational
      studies, updating the existing review by Jepson and coll. (Health Technol Assess.
      2000;4(14):i-vii, 1-133). RESULTS: 5900 have been identified, 900 relevant for
      the topic.Among those, 148 reported quantitative information on intervention
      efficacy, other 90 came from the previous review. Organised screening programmes,
      based on invitation letter or on GP involvement,were consistently effective in
      increasing participation compared to spontaneous screening. Interventions are
      classified according to their target: individual, community, test simplification,
      health operators, health service organization. The report presents meta-analyses
      on efficacy, analyses of cost-effectiveness, impact on organisation and social
      inequality, and ethical and legal issues, of all the intervention reported in the
      literature. CONCLUSIONS: there are several interventions consistently effective
      in any context, some of them have minimal impact on costs and health service
      resources.

PMID- 22418842
TI  - Nucleolar disruption leads to the spatial separation of key 18S rRNA processing
      factors.
AB  - Many chemotherapeutic drugs cause the downregulation of ribosome production and
      the disruption of nucleolar function. This stabilizes p53 and leads to either
      cell cycle arrest or apoptosis. It is not clear, however, how these agents cause
      nucleolar disruption and block ribosome production. The small subunit (SSU)
      processome, which has been primarily studied in yeast, is responsible for the
      processing of the 18S rRNA and assembly of the small ribosomal subunit. Here we
      have characterized the human homologs of seven SSU processome components.
      Furthermore, we have investigated the effects of three chemotherapeutic drugs,
      Actinomycin D (ActD), camptothecin (CPT) and 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole (DRB) on the subcellular distribution of key SSU
      processome components and the formation of this processing complex.
      Interestingly, ActD- and DRB-treatment resulted in the majority of U3 small
      nucleolar RNP (snoRNP) localizing separately to other key components of the SSU
      processome. All three agents affected RNA polymerase I transcription, primarily
      at the level of elongation but only ActD resulted in a clear reduction in SSU
      processome levels. Taken together, our data indicate that different
      chemotherapeutic agents, each of which initiates a stress response and cause
      nucleolar disruption, have different effects on the formation and localization of
      the SSU processome.

PMID- 22418843
TI  - Human RioK3 is a novel component of cytoplasmic pre-40S pre-ribosomal particles.
AB  - Maturation of the 40S ribosomal subunit precursors in mammals mobilizes several
      non-ribosomal proteins, including the atypical protein kinase RioK2. Here, we
      have investigated the involvement of another member of the RIO kinase family,
      RioK3, in human ribosome biogenesis. RioK3 is a cytoplasmic protein that does not
      seem to shuttle between nucleus and cytoplasm via a Crm1-dependent mechanism as
      does RioK2 and which sediments with cytoplasmic 40S ribosomal particles in a
      sucrose gradient. When the small ribosomal subunit biogenesis is impaired by
      depletion of either rpS15, rpS19 or RioK2, a concomitant decrease in the amount
      of RioK3 is observed. Surprisingly, we observed a dramatic and specific increase
      in the levels of RioK3 when the biogenesis of the large ribosomal subunit is
      impaired. A fraction of RioK3 is associated with the non ribosomal pre-40S
      particle components hLtv1 and hEnp1 as well as with the 18S-E pre-rRNA indicating
      that it belongs to a bona fide cytoplasmic pre-40S particle. Finally, RioK3
      depletion leads to an increase in the levels of the 21S rRNA precursor in the 18S
      rRNA production pathway. Altogether, our results strongly suggest that RioK3 is a
      novel cytoplasmic component of pre-40S pre-ribosomal particle(s) in human cells,
      required for normal processing of the 21S pre-rRNA.

PMID- 22418844
TI  - Distinct families of cis-acting RNA replication elements epsilon from hepatitis B
      viruses.
AB  - The hepadnavirus encapsidation signal, epsilon (epsilon), is an RNA structure
      located at the 5' end of the viral pregenomic RNA. It is essential for viral
      replication and functions in polymerase protein binding and priming. This
      structure could also have potential regulatory roles in controlling the
      expression of viral replicative proteins. In addition to its structure, the
      primary sequence of this RNA element has crucial functional roles in the viral
      lifecycle. Although the epsilon elements in hepadnaviruses share common critical
      functions, there are some significant differences in mammalian and avian
      hepadnaviruses, which include both sequence and structural variations. Here we
      present several covariance models for epsilon elements from the Hepadnaviridae.
      The model building included experimentally determined data from previous studies
      using chemical probing and NMR analysis. These models have sufficient similarity
      to comprise a clan. The clan has in common a highly conserved overall structure
      consisting of a lower-stem, bulge, upper-stem and apical-loop.   The models
      differ in functionally critical regions-notably the two types of avian epsilon
      elements have a tetra-loop (UGUU) including a non-canonical UU base pair, while
      the hepatitis B virus (HBV) epsilon has a tri-loop (UGU). The avian epsilon
      elements have a less stable dynamic structure in the upper stem. Comparisons
      between these models and all other Rfam models, and searches of genomes, showed
      these structures are specific to the Hepadnaviridae. Two family models and the
      clan are available from the Rfam database.

PMID- 22418845
TI  - A survey of sRNA families in alpha-proteobacteria.
AB  - We have performed a computational comparative analysis of six small non-coding
      RNA (sRNA) families in alpha-proteobacteria. Members of these families were first
      identified in the intergenic regions of the nitrogen-fixing endosymbiont S.
      meliloti by a combined bioinformatics screen followed by experimental
      verification. Consensus secondary structures inferred from covariance models for
      each sRNA family evidenced in some cases conserved motifs putatively relevant to
      the function of trans-encoded base-pairing sRNAs i.e., Hfq-binding signatures and
      exposed anti Shine-Dalgarno sequences. Two particular family models, namely
      alphar15 and alphar35, shared own sub-structural modules with the Rfam model suhB
      (RF00519) and the uncharacterized sRNA family alphar35b, respectively. A third
      sRNA family, termed alphar45, has homology to the cis-acting regulatory element
      speF (RF00518). However, new experimental data further confirmed that the S.
      meliloti alphar45 representative is an Hfq-binding sRNA processed from or
      expressed independently of speF, thus refining the Rfam speF model annotation.
      All the six families have members in phylogenetically related plant-interacting
      bacteria and animal pathogens of the order of the Rhizobiales, some occurring
      with high levels of paralogy in individual genomes. In silico and experimental
      evidences predict differential regulation of paralogous sRNAs in S. meliloti
      1021. The distribution patterns of these sRNA families suggest major
      contributions of vertical inheritance and extensive ancestral duplication events
      to the evolution of sRNAs in plant-interacting bacteria.

PMID- 22418846
TI  - HSP90 and the R2TP co-chaperone complex: building multi-protein machineries
      essential for cell growth and gene expression.
AB  - HSP90 (Heat Shock Protein 90) is an essential chaperone involved in the last
      folding steps of client proteins. It has many clients, and these are often
      recognized through specific adaptors. Recently, the conserved R2TP complex was
      identified as a key HSP90 co-chaperone. Current evidences indicate that the
      HSP90/R2TP system assembles multi-molecular protein complexes. Strikingly, these
      comprise basic machineries of gene expression: (1) nuclear RNA polymerases; (2)
      the snoRNPs, essential to produce ribosomes; and (3) mTOR Complex 1 and 2, which
      control translational activity and cell growth. Another important substrate is
      the telomerase RNP, required for continuous cell proliferation. We discuss here
      the assembly of RNA polymerases in bacteria and eukaryotes, the role of
      HSP90/R2TP in this process and in the assembly of snoRNPs and the PIKK family of
      TORC1 kinase. Finally, we speculate on the roles of R2TP as a master regulator of
      cell growth under normal or pathological conditions.

PMID- 22418847
TI  - Drastic expression change of transposon-derived piRNA-like RNAs and microRNAs in
      early stages of chicken embryos implies a role in gastrulation.
AB  - Recent studies have shown that endogenous small RNAs regulate a variety of
      biological processes during vertebrate development; however, little is known
      about the role of small RNAs in regulating developmental signaling pathways
      during early embryogenesis. In this study, we applied Illumina sequencing to
      characterize an unexpected endogenous small RNA catalog and demonstrated a
      dramatic transition from transposon-derived piRNA-like small RNAs (pilRNAs) to
      microRNAs (miRNAs) in pre- and post-gastrula chicken embryos. The comprehensive
      expression profile of chicken miRNAs at the pre- and post-gastrula stages
      revealed that most known and new miRNAs were dynamically regulated during
      development. In addition to embryonic stem cell-related miRNAs, Gene Ontology
      (GO) analysis showed that miRNAs enriched in early stage chicken embryos targeted
      multiple signal transduction pathways associated with the reproductive process
      and embryogenesis, including Wnt and TGF-beta, which specifies the neural fate of
      blastodermal cells. Intriguingly, a large cohort of pilRNAs primarily derived
      from the active and most abundant transposable elements (TEs) were enriched in
      chicken stage X blastoderms. Within stage X blastoderms, pilRNAs were
      specifically localized to the primordial germ cells (PGCs), indicating their post
      zygotic origin. Together, these findings imply a role for small RNAs in
      gastrulation in early stage chicken embryos.

PMID- 22418849
TI  - Identifying complete RNA structural ensembles including pseudoknots.
AB  - The close relationship between RNA structure and function underlines the
      significance of accurately predicting RNA structures from sequence information.
      Structural topologies such as pseudoknots are of particular interest due to their
      ubiquity and direct involvement in RNA function, but identifying pseudoknots is a
      computationally challenging problem and existing heuristic approaches usually
      perform poorly for RNA sequences of even a few hundred bases. We survey the
      performance of pseudoknot prediction methods on a data set of full-length RNA
      sequences representing varied sequence lengths, and biological RNA classes such
      as RNase P RNA, Group I Intron, tmRNA and tRNA. Pseudoknot prediction methods are
      compared with minimum free energy and suboptimal secondary structure prediction
      methods in terms of correct base-pairs, stems and pseudoknots and we find that
      the ensemble of suboptimal structure predictions succeeds in identifying correct
      structural elements in RNA that are usually missed in MFE and pseudoknot
      predictions. We propose a strategy to identify a comprehensive set of non
      redundant stems in the suboptimal structure space of a RNA molecule by applying
      heuristics that reduce the structural redundancy of the predicted suboptimal
      structures by merging slightly varying stems that are predicted to form in local
      sequence regions. This reduced-redundancy set of structural elements consistently
      outperforms more specialized approaches.in data sets. Thus, the suboptimal
      folding space can be used to represent the structural diversity of an RNA
      molecule more comprehensively than optimal structure prediction approaches alone.

PMID- 22418848
TI  - A domain-based model for predicting large and complex pseudoknotted structures.
AB  - Pseudoknotted structures play important structural and functional roles in RNA
      cellular functions at the level of transcription, splicing and translation.
      However, the problem of computational prediction for large pseudoknotted folds
      remains. Here we develop a domain-based method for predicting complex and large
      pseudoknotted structures from RNA sequences. The model is based on the
      observation that large RNAs can be separated into different structural domains.
      The basic idea is to first identify the domains and then predict the structures
      for each domain. Assembly of the domain structures gives the full structure. The
      use of the domain-based approach leads to a reduction of computational time by a
      factor of about ~N ( 2)  for an N-nt sequence. As applications of the model, we
      predict structures for a variety of RNA systems, such as regions in human
      telomerase RNA (hTR), internal ribosome entry site (IRES) and HIV genome. The
      lengths of these sequences range from 200-nt to 400-nt. The results show good
      agreements with the experiments.

PMID- 22418850
TI  - Impaired apoptosis of megakaryocytes and bone marrow mononuclear cells in
      essential thrombocythemia: correlation with JAK2V617F mutational status and
      cytoreductive therapy.
AB  - Essential thrombocythemia (ET) is a clonal myeloproliferative disorder
      characterized by overproduction of megakaryocytes (MKCs) and platelets. The
      recent discovery of the JAK2 mutation has shed a new light on the development of
      ET but its pathogenesis still remains unknown. One of the possible mechanisms can
      be deregulation of apoptosis, resulting in accumulation of bone marrow MKCs. In
      this study, we investigated the apoptotic profile, as well as the expression of
      apoptosis-regulating protein in MKCs and bone marrow mononuclear cells (BMMCs) in
      43 patients with ET. We found significantly lower percentages of apoptotic MKCs
      and BMMCs, as measured by the rate of annexin-V+ and caspase-3+ (Cas-3+) cells in
      relation to healthy volunteers. Additionally, the expression of Bax protein in ET
      patients naive to cytoreductive treatment, as well as their Bax/Bcl-2 ratio, was
      significantly lower than in controls (p=<0.05 and p<0.001, respectively).
      Patients positive for the JAK2V617F mutation had markedly higher activation of
      Cas-3, as well as higher Bax expression (p=0.02 and p=0.04, respectively) than
      JAK2V617F negative cases. There were no marked differences between patients
      already treated with anagrelide (ANA) or hydroxyurea (HU), although tendency
      toward the higher apoptosis rate was observed in the HU-treated group. In
      conclusion, these results demonstrate the inhibition of caspase-dependent
      apoptosis of both MKCs and BMMCs in untreated ET. This is associated with
      upregulation of Bcl-2 and downregulation of Bax proteins, predominantly in
      JAK2V617F negative cases. Patients treated with HU showed slightly higher pro
      apoptotic Bax/Bcl-2 index than patients on ANA therapy, which may influence the
      better efficacy of HU therapy in ET.

PMID- 22418851
TI  - Adjuvant chemoradiotherapy (CRT) for high-risk gastric cancer (GC) patients:
      single-center experience using infusional 5-fluorouracil (5FU) and radiotherapy
      (RT).

PMID- 22418852
TI  - Demographic and clinico-pathological characteristics of breast cancer patients
      with history of oral alendronate use.
AB  - Bisphosphonates are the most commonly used agents in the treatment of
      osteoporosis, and bisphosphonate therapy reduces the risk of skeletally related
      complications in patients with bone metastases due to malignancy. However, the
      effect of oral alendronate treatment on clinical and pathological properties of
      breast cancer has not been reported. Thus, we aimed to investigate
      retrospectively the demographic and clinico-pathological characteristics of new
      diagnosis of breast cancer patients with oral alendronate users for longer than 1
      year, compared with non-users. Newly diagnosed breast cancer patients from 1998
      to 2010 in our clinic were retrospectively analyzed. Patient's demographics,
      including survival data and tumor characteristics, were obtained from medical
      charts. Breast cancer patients who were taking oral alendronate more than 12
      months at the time of breast cancer diagnosis were enrolled as an alendronate
      users (n=44), where the patients matched with the same age who were not taking
      oral alendronate were included as a control group (n=444). A total of 488
      patients were included in this study. Forty-four patients received an oral
      alendronate treatment more than 1 year, and 444 patients were considered as non
      users. Median age of both alendronate users and non-users was 57 (33-89). Lower
      incidence of histological grade III, T3-T4 tumor, and node positivity was seen in
      alendronate users but not statistically significant. A similar trend for lower
      incidence of triple negative and higher incidence ER (P=0.13), progesterone
      receptor (P=0.12), and HER2 positivity (P=0.21) was also seen in alendronate
      users but not statistically significant. Estimated median disease-free survival
      was 150 months in alendronate users where as 70 months in non-users (P=0.015).
      Five-year survival rate in alendronate users was 97.4%, whereas in non-users was
      89.8% (P=0.13). The use of oral alendronate for longer than 1 year at the time of
      breast cancer diagnosis was associated with better clinico-pathological
      properties and significantly improved disease-free survival in breast cancer
      patients.

PMID- 22418853
TI  - Impact of anastomotic complications on outcome after laparoscopic gastrectomy for
      early gastric cancer.
AB  - BACKGROUND: The effects of anastomotic complications after laparoscopically
      assisted gastrectomy (LAG) have not been studied widely. The aims of this
      observational study were to identify potential factors that predict anastomotic
      complications and investigate the impact of anastomotic complications in patients
      undergoing gastrectomy for early gastric cancer. METHODS: The study included
      consecutive patients with histologically proven T1 gastric adenocarcinoma treated
      by LAG with regional lymphadenectomy between August 1997 and March 2008, who had
      not received neoadjuvant chemotherapy. Anastomotic complications included
      anastomotic leakage, stricture and remnant gastric stasis of grade II or higher
      (modified Clavien classification) and were identified by clinical assessment and
      confirmatory investigation. Predictive factors for the development of anastomotic
      complications were identified by univariable and multivariable analyses. Long
      term survival with or without anastomotic complications was examined. RESULTS:
      Anastomotic complications occurred in 37 (9.3 per cent) of 400 patients.
      Multivariable analysis indicated surgeon experience as the only independent
      predictor of anastomotic complications (hazard ratio 4.40, 95 per cent confidence
      interval 2.04 to 9.53; P < 0.001). Patients with anastomotic complications had a
      significantly worse overall 5-year survival rate than those without (81 versus
      94.2 per cent; P = 0.009). CONCLUSION: Anastomotic complications after LAG lead
      to worse long-term survival.

PMID- 22418854
TI  - Statistical quality control of total ash, acid-insoluble ash, loss on drying, and
      hazardous heavy metals contained in the component medicinal herbs of
      "Ssanghwatang", a widely used oriental formula in Korea.
AB  - To investigate the current quality control status of raw materials in
      "Ssanghwatang", a widely used oriental formula effective for fatigue recovery in
      Korea, 1024 samples of 9 herbs available in Seoul area markets were collected,
      and the contents of quality inspection items such as total ash, acid-insoluble
      ash, loss on drying, and hazardous heavy metals (Pb, As, Cd, Hg) were examined.
      Medicinal herbs requiring quality control, which may not meet the specifications
      and standards set by the Korea Food and Drug Administration, were selected using
      robust z-scores, a random variable. Among the quality control items, control of
      total ash content was required for the Ssanghwatang raw materials Cinnamomi
      Cortex, Rehmanniae Radix Preparata, Zingiberis Rhizoma, and Zizyphi Fructus; loss
      on drying for Cinnamomi Cortex; and heavy metal (Cd) for Angelicae Gigantis
      Radix, Cinnamomi Cortex, and Zingiberis Rhizoma. Additionally, acid-insoluble ash
      content revealed how many fine soil and sand particles are present in commercial
      medicinal herbs, which were correlated with heavy metals such as Pb (r = 0.528)
      and As (r = 0.342) in Rehmanniae Radix Preparata (p < 0.01).

PMID- 22418855
TI  - Effect of dietary caraway essential oils on expression of beta-catenin during 1,2
      dimethylhydrazine-induced colonic carcinogenesis.
AB  - We have recently reported that the inhibition of colonic premalignant lesions
      induced by 1,2-dimethylhydrazine (DMH) is mediated by the interference of caraway
      oil components in the activities of the main hepatic xenobiotic metabolizing
      enzymes. The present study was carried out to examine the effect of dietary
      caraway oils on the progression of cancer, with emphasis on beta-catenin
      expression in the colon during DMH-induced colonic carcinogenesis. For this
      purpose, colon cancer was induced by DMH in rats (20 mg/kg body weight for 5
      weeks) and groups of animals were given dietary caraway essential oils at two
      levels (0.01 and 0.1%) for 16 weeks. After 16 weeks and at the end of the
      experimental period the colon tissue biopsies were processed for
      histopathological examination and the expression of beta-catenin at mRNA and
      protein levels was estimated by polymerase chain reaction and enzyme-linked
      immunosorbent assay. The formation of premalignant lesions based on aberrant
      crypt foci (ACF) in DMH-treated rats was greatly inhibited (72-87%) in rats given
      dietary essential oils when compared to respective controls. There was a
      correlation between the number of colonic ACF formation and the expression levels
      of beta-catenin measured at protein and mRNA levels. These results indicate that
      the Wnt/beta-catenin signaling pathway is activated during colon cancer promotion
      and that the expression of colonic beta-catenin is altered in long-term caraway
      oil feeding, leading to suppression of DMH-induced premalignant lesions in rat
      colon.

PMID- 22418856
TI  - Systematic review and meta-analysis of the efficacy of cardioversion by
      vernakalant and comparators in patients with atrial fibrillation.
AB  - PURPOSE: Rate and rhythm control are two well established treatment objectives
      for atrial fibrillation (AF) patients. While symptom reduction is a primary
      treatment goal, therapeutic practice related to cardioversion varies by region
      and patient, with several precautions associated with the use of current
      therapies. No comprehensive literature review on the relative efficacy of
      existing cardioversion approaches compared to newly available therapies has been
      conducted. METHODS AND RESULTS: A systematic literature review and meta-analysis
      were undertaken to evaluate the efficacy of pharmacologic therapies in eliciting
      cardioversion within 2 and 8-24 h among patients with recent-onset, short
      duration AF. Eligible studies included randomized controlled trials in which
      cardioversion rates were evaluated in at least 2 treatment groups. Bayesian mixed
      treatment comparisons estimated odds ratios (95% credible intervals) for
      successful cardioversion. Results within 2 h showed vernakalant IV, propafenone
      IV and flecainide (IV and oral) were more efficacious in pair-wise comparisons to
      placebo. Results were mixed in analyses comparing efficacy rates between 8 and 24
      h. Few adverse events were reported, with the most common being bradycardia and
      hypotension. CONCLUSIONS: In pair-wise comparisons of active treatment arms to
      one another, results suggest vernakalant IV, propafenone IV and flecainide appear
      to be effective in achieving rapid cardioversion in patients with short duration
      AF compared to other agents. Application of these findings to clinical practice
      need to account for the variable comorbidity profiles of patients, important
      determinants in the selection of appropriate therapy for individual patients.
      Though best practice methods were used, further research comparing treatments
      through direct head-to-head comparisons may be warranted to confirm these
      findings and further inform clinical practice.

PMID- 22418857
TI  - Prognostic influence of BCL2 expression in breast cancer.
AB  - Although BCL2 has occasionally been suggested as a candidate prognostic factor
      for breast cancer, it is still not accepted as a prognostic factor. We attempted
      to validate the role of BCL2 as a prognostic factor of breast cancer. Data on
      7,230 primary breast cancer patients from the Seoul National University Hospital
      Breast Care Center were analyzed. Three current prognostic models, including the
      St. Gallen model, the Nottingham prognostic index (NPI) model and the TNM model,
      were used for analysis of the prognostic influence of BCL2. The positive BCL2
      group showed more favorable features with regard to clinicopathologic parameters
      than the BCL2 negative group and a strong correlation was observed between BCL2
      and the hormonal receptor. The positive BCL2 group showed better prognosis in
      overall survival and disease free survival (log-rank test, both p < 0.001), even
      in all subgroups, than the BCL2 negative group. BCL2 was a significant prognostic
      factor in both univariate (hazard ratio [HR], 0.361; 95% confidence interval
      (CI), 0.306-0.426; p < 0.001) and multivariate analyses (HR, 0.417; 95% CI, 0.417
      0.705; p < 0.001). BCL2 had a strong influence on the established prognostic
      models, including the St. Gallen model, the NPI model and the TNM model. BCL2 was
      a powerful independent prognostic factor for breast cancer and had a strong
      influence on the current prognostic models. Favorable clinicopathologic features
      and a strong correlation with the hormonal receptor are suggested as the causes
      of superior survival in patients with BCL2 positive breast cancer.

PMID- 22418859
TI  - Social familiarity modulates group living and foraging behaviour of juvenile
      predatory mites.
AB  - Environmental stressors during early life may have persistent consequences for
      phenotypic development and fitness. In group-living species, an important
      stressor during juvenile development is the presence and familiarity status of
      conspecific individuals. To alleviate intraspecific conflicts during juvenile
      development, many animals evolved the ability to discriminate familiar and
      unfamiliar individuals based on prior association and use this ability to
      preferentially associate with familiar individuals. Assuming that familiar
      neighbours require less attention than unfamiliar ones, as predicted by limited
      attention theory, assorting with familiar individuals should increase the
      efficiency in other tasks. We assessed the influence of social familiarity on
      within-group association behaviour, development and foraging of juvenile life
      stages of the group-living, plant-inhabiting predatory mite Phytoseiulus
      persimilis. The observed groups consisted either of mixed-age familiar and
      unfamiliar juvenile mites or of age-synchronized familiar or unfamiliar juvenile
      mites or of pairs of familiar or unfamiliar larvae. Overall, familiar mites
      preferentially grouped together and foraged more efficiently, i.e. needed less
      prey at similar developmental speed and body size at maturity, than unfamiliar
      mites. Preferential association of familiar mites was also apparent in the inter
      exuviae distances. Social familiarity was established by imprinting in the larval
      stage, was not cancelled or overridden by later conspecific contacts and
      persisted into adulthood. Life stage had an effect on grouping with larvae being
      closer together than nymphal stages. Ultimately, optimized foraging during the
      developmental phase may relax within-group competition, enhance current and
      future food supply needed for optimal development and optimize patch exploitation
      and leaving under limited food.

PMID- 22418858
TI  - Performance and scaling effects in a multilayer microfluidic extracorporeal lung
      oxygenation device.
AB  - Microfluidic fabrication technologies are emerging as viable platforms for
      extracorporeal lung assist devices and oxygenators for cardiac surgical support
      and critical care medicine, based in part on their ability to more closely mimic
      the architecture of the human vasculature than existing technologies. In
      comparison with current hollow fiber oxygenator technologies, microfluidic
      systems have more physiologically-representative blood flow paths, smaller cross
      section blood conduits and thinner gas transfer membranes. These features can
      enable smaller device sizes and a reduced blood volume in the oxygenator,
      enhanced gas transfer efficiencies, and may also reduce the tendency for clotting
      in the system. Several critical issues need to be addressed in order to advance
      this technology from its current state and implement it in an organ-scale device
      for clinical use. Here we report on the design, fabrication and characterization
      of multilayer microfluidic oxygenators, investigating scaling effects associated
      with fluid mechanical resistance, oxygen transfer efficiencies, and other
      parameters in multilayer devices. Important parameters such as the fluidic
      resistance of interconnects are shown to become more predominant as devices are
      scaled towards many layers, while other effects such as membrane distensibility
      become less significant. The present study also probes the relationship between
      blood channel depth and membrane thickness on oxygen transfer, as well as the
      rate of oxygen transfer on the number of layers in the device. These results
      contribute to our understanding of the complexity involved in designing three
      dimensional microfluidic oxygenators for clinical applications.

PMID- 22418860
TI  - Restricted gene flow and fine-scale population structuring in tool using New
      Caledonian crows.
AB  - New Caledonian crows Corvus moneduloides are the most prolific avian tool users.
      It has been suggested that some aspects of their complex tool use behaviour are
      under the influence of cultural processes, involving the social transmission-and
      perhaps even progressive refinement-of tool designs. Using microsatellite and mt
      haplotype profiling of crows from three distinct habitats (dry forest, farmland
      and beachside habitat), we show that New Caledonian crow populations can exhibit
      significant fine-scale genetic structuring. Our finding that some sites of <10 km
      apart were highly differentiated demonstrates considerable potential for genetic
      and/or cultural isolation of crow groups. Restricted movement of birds between
      local populations at such small spatial scales, especially across habitat
      boundaries, illustrates how specific tool designs could be preserved over time,
      and how tool technologies of different crow groups could diverge due to drift and
      local selection pressures. Young New Caledonian crows have an unusually long
      juvenile dependency period, during which they acquire complex tool-related
      foraging skills. We suggest that the resulting delayed natal dispersal drives
      population-divergence patterns in this species. Our work provides essential
      context for future studies that examine the genetic makeup of crow populations
      across larger geographic areas, including localities with suspected cultural
      differences in crow tool technologies.

PMID- 22418861
TI  - Cantilever arrays with self-aligned nanotips of uniform height.
AB  - Cantilever arrays are employed to increase the throughput of imaging and
      manipulation at the nanoscale. We present a fabrication process to construct
      cantilever arrays with nanotips that show a uniform tip-sample distance. Such
      uniformity is crucial, because in many applications the cantilevers do not
      feature individual tip-sample spacing control. Uniform cantilever arrays lead to
      very similar tip-sample interaction within an array, enable non-contact modes for
      arrays and give better control over the load force in contact modes. The
      developed process flow uses a single mask to define both tips and cantilevers. An
      additional mask is required for the back side etch. The tips are self-aligned in
      the convex corner at the free end of each cantilever. Although we use standard
      optical contact lithography, we show that the convex corner can be sharpened to a
      nanometre scale radius by an isotropic underetch step. The process is robust and
      wafer-scale. The resonance frequencies of the cantilevers within an array are
      shown to be highly uniform with a relative standard error of 0.26% or lower. The
      tip-sample distance within an array of up to ten cantilevers is measured to have
      a standard error around 10 nm. An imaging demonstration using the AFM shows that
      all cantilevers in the array have a sharp tip with a radius below 10 nm. The
      process flow for the cantilever arrays finds application in probe-based
      nanolithography, probe-based data storage, nanomanufacturing and parallel
      scanning probe microscopy.

PMID- 22418862
TI  - Ictal focal hyperperfusion demonstrated by arterial spin-labeling perfusion MRI
      in partial epilepsy status.

PMID- 22418863
TI  - Selective deuteration of (hetero)aromatic compounds via deutero-decarboxylation
      of carboxylic acids.
AB  - A practical, mild and highly selective protocol for the monodeuteration of a
      variety of arenes and heteroarenes is presented. Catalytic amounts of Ag(I) salts
      in DMSO/D(2)O are shown to facilitate the deutero-decarboxylation of ortho
      substituted benzoic and heteroaromatic alpha-carboxylic acids in high yields with
      excellent levels of deuterium incorporation.

PMID- 22418864
TI  - Synthesis of hydroxydiamines and triamines via reductive cleavage of N-N bond in
      substituted pyrazolidines.
AB  - Aliphatic polyamines, being a versatile class of organic compounds, are widely
      used in many fields of medicine and organic chemistry. However, the general
      approach to the synthesis of chiral aliphatic polyamines has been still
      undeveloped. Here, we describe a new method for the synthesis of chiral
      trifunctional amino compounds, namely hydroxydiamines and triamines. The initial
      compounds, namely substituted hydroxy- or aminopyrazolidines and pyrazolines, are
      readily available using convenient stereoselective methods developed earlier by
      us. The proposed method allows synthesizing of chiral diaminoalcohols and
      triamines, which are the analogs of a well-known anti-TB drug, namely ethambutol,
      and cannot be obtained alternatively. The key step of the synthesis is N-N bond
      cleavage in substituted hydroxy- or aminopyrazolidines and pyrazolines with
      borane-tetrahydrofuran complex; other known methods for N-N bond cleavage turned
      out to be ineffective. The main advantage of the proposed method is the retention
      of a certain configuration of stereocenters in the course of the reaction. Six
      new chiral diasteomerically pure substituted hydroxydiamines and triamines and
      the enantiomerically pure triamine with four chiral centers were synthesized and
      characterized using NMR, IR and mass spectroscopy, as well as elemental analysis.

PMID- 22418865
TI  - Taurine supplementation prevents morpho-physiological alterations in high-fat
      diet mice pancreatic beta-cells.
AB  - Taurine (Tau) is involved in beta (beta)-cell function and insulin action
      regulation. Here, we verified the possible preventive effect of Tau in high-fat
      diet (HFD)-induced obesity and glucose intolerance and in the disruption of
      pancreatic beta-cell morpho-physiology. Weaning Swiss mice were distributed into
      four groups: mice fed on HFD diet (36 % of saturated fat, HFD group); HTAU, mice
      fed on HFD diet and supplemented with 5 % Tau; control (CTL); and CTAU. After 19
      weeks of diet and Tau treatments, glucose tolerance, insulin sensitivity and
      islet morpho-physiology were evaluated. HFD mice presented higher body weight and
      fat depots, and were hyperglycemic, hyperinsulinemic, glucose intolerant and
      insulin resistant. Their pancreatic islets secreted high levels of insulin in the
      presence of increasing glucose concentrations and 30 mM K(+). Tau supplementation
      improved glucose tolerance and insulin sensitivity with a higher ratio of Akt
      phosphorylated (pAkt) related to Akt total protein content (pAkt/Akt) following
      insulin administration in the liver without altering body weight and fat
      deposition in HTAU mice. Isolated islets from HTAU mice released insulin
      similarly to CTL islets. HFD intake induced islet hypertrophy, increased beta
      cell/islet area and islet and beta-cell mass content in the pancreas. Tau
      prevented islet and beta-cell/islet area, and islet and beta-cell mass
      alterations induced by HFD. The total insulin content in HFD islets was higher
      than that of CTL islets, and was not altered in HTAU islets. In conclusion, for
      the first time, we showed that Tau enhances liver Akt activation and prevents
      beta-cell compensatory morpho-functional adaptations induced by HFD.

PMID- 22418866
TI  - Metabolism of amino acids during hyposmotic adaptation in the whiteleg shrimp,
      Litopenaeus vannamei.
AB  - The penaeid prawn, Litopenaeus vannamei, was employed to investigate
      intracellular isosmotic regulation in situations where invertebrates encounter
      hyposmosis. Hemolymph osmolality was first analyzed to confirm osmoregulatory
      conditions in the experimental animals, followed by analysis of amino acids in
      muscle and hemolymph using high-performance liquid chromatography. Total muscle
      amino acid levels decreased when hemolymph osmolality was extremely low, whereas
      glycine and L-serine levels increased in the hemolymph. These results suggest
      that tissue amino acids were released into the hemolymph to lower the osmolality
      of the tissues for purposes of low-salinity adaptation. Next, oxygen consumption
      and ammonia excretion rates were examined, and the O/N ratio was determined.
      Oxygen consumption levels and ammonia excretion rates increased, and the O/N
      ratio decreased when the animals were exposed to low salinity. These results
      suggest that amino acids were abundantly consumed as an energy source when
      animals were exposed to low salinity. To confirm the consumption of particular
      amino acids, the specific activity of L-serine ammonia lyase was also examined.
      Specific activity was highest when L-serine levels in the hemolymph were highest.
      Thus, it appears that L-serine levels increased under hyposmotic conditions due
      to the consumption of L-serine as an energy source. It was concluded that
      particular amino acids as osmolytes are likely metabolized as energy sources and
      consumed for purposes of hyposmotic adaptation.

PMID- 22418867
TI  - Role and regulation of STAT3 phosphorylation at Ser727 in melanocytes and
      melanoma cells.
AB  - The transcription factor signal transducer and activator of transcription 3
      (STAT3) has two important phosphorylation sites, Tyr705 and Ser727, for its
      activation. Ser727 phosphorylation has been considered to be a secondary event
      after Tyr705 phosphorylation. In this study, the role and regulation of Ser727
      phosphorylation in STAT3 in melanocytic cells were examined. STAT3 was
      phosphorylated on Ser727 in the absence of Tyr705 phosphorylation in melanocytes.
      12-O-tetradecanoylphorbol-13-acetate-induced increase in cell survival activity
      and nuclear translocation of STAT3 was associated with Ser727 phosphorylation.
      Ser727 was constitutively phosphorylated in all melanoma cell lines examined
      irrespective of Tyr705 phosphorylation. The possible involvement of Ser727
      phosphorylation in STAT3 in cell survival activity and nuclear translocation of
      STAT3 in melanocytes was demonstrated also in melanoma cells. The constitutive
      Ser727 phosphorylation in melanoma cells was partially mediated by the B-Raf-MEK
      ERK1/2 pathway. Immunohistochemical studies on specimens of primary lesions of
      acral lentiginous melanoma revealed that Ser727 phosphorylation precedes Tyr705
      phosphorylation in the early stages of melanoma progression. Our results indicate
      that Ser727 phosphorylation on STAT3 is not necessarily a secondary event after
      Tyr705 phosphorylation and suggest that it has a role in the regulation of cell
      survival activity and nuclear translocation of STAT3 in melanocytic cells.

PMID- 22418869
TI  - Atopic keratinocytes induce increased neurite outgrowth in a coculture model of
      porcine dorsal root ganglia neurons and human skin cells.
AB  - Skin of patients suffering from atopic eczema displays a higher epidermal nerve
      fiber density, associated with neurogenic inflammation and pruritus. Using an in
      vitro coculture system, allowing a spatially compartmented culture of somata from
      porcine dorsal root ganglion neurons and human primary skin cells, we
      investigated the influence of dermal fibroblasts and keratinocytes on neurite
      outgrowth. In comparison with dermal fibroblasts, keratinocytes induced more
      branched and less calcitonin gene-related peptide (CGRP)-immunoreactive nerve
      fibers. By adding neutralizing antibodies, we showed that nerve growth factor
      (NGF) and glial cell-line-derived neurotrophic factor (GDNF) are pivotal
      neurotrophic factors of skin cell-induced neurite outgrowth. Keratinocytes and
      dermal fibroblasts secreted different ratios of neurotrophic factors, influencing
      morphology and CGRP immunoreactivity of neurites. To investigate changes of the
      peripheral nervous system in the pathogenesis of atopic eczema in vitro, we
      analyzed neurite outgrowth mediated by atopic skin cells. Atopic keratinocytes
      produced elevated levels of NGF and mediated an increased outgrowth of CGRP
      positive sensory fibers. Our results demonstrate the impact of dermal fibroblasts
      and keratinocytes on skin innervation and emphasize the role of keratinocytes as
      key players of hyperinnervation in atopic eczema.

PMID- 22418868
TI  - Urea uptake enhances barrier function and antimicrobial defense in humans by
      regulating epidermal gene expression.
AB  - Urea is an endogenous metabolite, known to enhance stratum corneum hydration.
      Yet, topical urea anecdotally also improves permeability barrier function, and it
      appears to exhibit antimicrobial activity. Hence, we hypothesized that urea is
      not merely a passive metabolite, but a small-molecule regulator of epidermal
      structure and function. In 21 human volunteers, topical urea improved barrier
      function in parallel with enhanced antimicrobial peptide (AMP; LL-37 and beta
      defensin-2) expression. Urea stimulates the expression of, and is transported
      into, keratinocytes by two urea transporters (UTs), UT-A1 and UT-A2, and by
      aquaporins 3, 7, and 9. Inhibitors of these UTs block the downstream biological
      effects of urea, which include increased mRNA and protein levels of (i)
      transglutaminase-1, involucrin, loricrin, and filaggrin, (ii) epidermal lipid
      synthetic enzymes, and (iii) cathelicidin/LL-37 and beta-defensin-2. Finally, we
      explored the potential clinical utility of urea, showing that topical urea
      applications normalized both barrier function and AMP expression in a murine
      model of atopic dermatitis. Together, these results show that urea is a small
      molecule regulator of epidermal permeability barrier function and AMP expression
      after transporter uptake, followed by gene regulatory activity in normal
      epidermis, with potential therapeutic applications in diseased skin.

PMID- 22418870
TI  - Interactions between genetic variants of FLG and chromosome 11q13 locus determine
      susceptibility for eczema phenotypes.

PMID- 22418871
TI  - alpha-MSH-stimulated tolerogenic dendritic cells induce functional regulatory T
      cells and ameliorate ongoing skin inflammation.
AB  - The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) is a well-known
      mediator of skin pigmentation. More recently, it has been shown that alpha-MSH
      also exerts a strong anti-inflammatory and immunosuppressive activity. To
      elucidate the mechanisms underlying alpha-MSH-induced immunosuppression, we
      investigated whether alpha-MSH affects dendritic cell/T cell communication, as
      especially this interaction has an important role in the regulation of immune
      responses. Here, we show that alpha-MSH, by binding to MC-1R, induced tolerogenic
      dendritic cells, which were capable of expanding CD4(+)CD25(+)Foxp3(+) regulatory
      T cells (Tregs) in vitro, as well as in vivo. Notably, those alpha-MSH-induced
      Tregs were functional as they efficiently inhibited cutaneous contact allergy and
      ongoing psoriasis-like skin inflammation in mice. Furthermore, alpha-MSH induced
      tolerogenic dendritic cells capable of generating functional Tregs in human
      blood. Interestingly, human Tregs expanded via alpha-MSH-stimulated dendritic
      cells suppressed the proliferation and cytokine secretion of pathogenic T-helper
      17 (Th17) cells from individuals with psoriasis. Taken together, these data
      indicate that alpha-MSH induced immunosuppressive Tregs in vitro and in vivo,
      which inhibited disease progression in a mouse model of psoriasis-like skin
      inflammation and suppressed the activation and proliferation of effector T cells
      from subjects with psoriasis.

PMID- 22418872
TI  - Incidence and mortality of bullous pemphigoid in France.
AB  - A major increase in the incidence of BP has been recently reported in the United
      Kingdom. In addition, there are some controversies about the over-mortality of BP
      patients. The primary objective was to reevaluate the incidence of BP in France
      as compared with that we estimated 15 years ago. The secondary objective was to
      assess mortality of BP patients. BP incidence was retrospectively estimated from
      all BP cases diagnosed between January 2000 and December 2005 in three French
      regions with a total population of 3.858 million inhabitants. BP mortality was
      assessed from a prospective cohort accrued during the same time period. A total
      of 502 incident BP patients (mean age: 82.6+/-8.8 years) were identified. Overall
      estimated incidence was 21.7 cases per million persons per year (95%CI:19.8-23.7
      cases per million persons per year), which is about 3-fold higher than the
      incidence that we estimated 15 years ago. In the population aged 70 years or
      above, BP incidence was 162 cases per million per year (95%CI:147-177 cases per
      million per year). The overall 1-year survival rate was 62% (95% CI: 56-67%). The
      risk of death for BP patients was more than six times greater than that for the
      general population (SMR:6.60; 95%CI:5.47-7.90). The incidence of BP in France has
      increased 3-fold in the last 15 years. BP is associated with high mortality.

PMID- 22418873
TI  - Botulinum neurotoxin A decreases infiltrating cutaneous lymphocytes and improves
      acanthosis in the KC-Tie2 mouse model.

PMID- 22418874
TI  - Willingness to pay in dermatology: assessment of the burden of skin diseases.
AB  - Willingness to pay (WTP) is a monetary, preference-based, burden-of-disease
      measure with a potential role in dermatology, where many conditions are temporary
      and/or mild, and many treatments are inexpensive and one might be able to imagine
      paying out of pocket. We assessed construct validity by interviewing 254
      consecutive dermatology patients at Stanford Medical Center, Grady Hospital, and
      Parkland Hospital. Instruments asked about an individual's own health status and
      elicited WTP, time-trade-off (TTO) utilities, and health status quality of life
      (QOL). We measured WTP cure (short treatment course to eliminate disease) and WTP
      control (lifelong medication). Our data indicate greater construct validity in
      non-Medicaid (n=163) than Medicaid (n=91) patients. Non-Medicaid subjects had
      greater WTP as percent of income for cure (median: 2%) than control (median:
      1.6%), P<0.01; Medicaid WTP amounts for control and cure did not differ. Non
      Medicaid subjects with verrucae had little QOL impact, no measurable burden by
      TTO, and a correspondingly low WTP. Medicaid subjects with basal cell carcinoma
      had a strong, negative QOL impact and high burden by TTO, but had relatively
      moderate WTP. WTP appears promising in certain income categories. More studies
      are needed for conclusions about specific diagnoses.

PMID- 22418876
TI  - Developing vaccines against virus infections: between hope and fear.
AB  - As a kid I dreamed of becoming a professional football player like many other
      boys. However, without the talent, I had to think of another professional career.
      After considering many different options while in high school, including becoming
      an architect, army officer or medical doctor, I finally decided to start a study
      Biology at the Free University of Amsterdam.  After two years I chose to become a
      medical biologist. Especially the mandatory internships at various research
      departments were of great interest and made me pursuing a career as biomedical
      researcher.

PMID- 22418875
TI  - Mouse model of touch-evoked itch (alloknesis).
AB  - Lightly touching normal skin near a site of itch can elicit itch sensation, a
      phenomenon known as alloknesis. To investigate the neural mechanisms of
      alloknesis, we have developed an animal model. Low-threshold mechanical
      stimulation of the skin normally does not elicit any response in naive C57/BL6
      mice. Following acute intradermal (i.d.) injection of histamine in the rostral
      back, mechanical stimulation 7 mm from the injection site elicited discrete
      hindlimb scratch bouts directed toward the stimulus. This began at 10 minutes and
      peaked 20-40 minutes post histamine injection, declining over the next hour.
      Histamine itself elicited bouts of scratching not associated with the mechanical
      stimulus, which ceased after 30 minutes. Histamine- and touch-evoked scratching
      was inhibited by the MU-opiate antagonist naltrexone. Touch-evoked scratching was
      observed following i.d. 5-HT (5-hydroxytryptamine), a protease-activated receptor
      (PAR)-4 agonist, and an MrgprC11 agonist BAM8-22, but not chloroquine or a PAR-2
      agonist. The histamine H1 receptor antagonist terfenadine prevented scratching
      and alloknesis evoked by histamine, but not 5-HT, a PAR-4 agonist or an MrgprC11
      agonist. In mice with experimental dry skin, there was a time-dependent increase
      in spontaneous and touch-evoked scratching. This animal model appears to be
      useful to investigate neural mechanisms of itch and alloknesis.

PMID- 22418877
TI  - Positive phase 2 results for immatics colorectal cancer vaccine.

PMID- 22418878
TI  - Letter from the editor.

PMID- 22418879
TI  - Quantifying the extent of fistulotomy. How much sphincter can we safely divide? A
      three-dimensional endosonographic study.
AB  - PURPOSE: To quantify the longitudinal division of the internal anal sphincter
      (IAS) and external anal sphincter (EAS) after fistulotomy using three-dimensional
      endoanal ultrasound (3D-EAUS) and correlate the results with postoperative faecal
      incontinence. METHODS: A prospective, consecutive study was performed from
      December 2008 to October 2010. All patients underwent 3D-EAUS before and 8 weeks
      after surgery. Thirty-six patients with simple perianal fistula were included.
      Patients with an intersphincteric or low transphincteric fistula (<66% sphincter
      involved) without risk factors for incontinence underwent fistulotomy. The
      outcome measures were the longitudinal extent of division of the IAS and EAS in
      relation to total sphincter length and continence (Jorge and Wexner scores).
      RESULTS: One-year follow-up revealed a 0% recurrence rate. There was a strong
      correlation between preoperative 3D-EAUS measurement of fistula height with
      intraoperative and postoperative 3D-EAUS measurement of IAS and EAS division (p <
      0.001). The relationship between the level of EAS division and faecal
      incontinence showed a significant difference in incontinence rates between
      fistulotomies limited to the lower two thirds of the EAS and those above this
      level. Five patients (13.9%) had worse anal continence after surgery, although
      this was mild in all patients (<3/20 Jorge and Wexner scale). There was no
      significant difference in continence scores before and after surgery (p > 0.05).
      CONCLUSIONS: In patients without risk factors, division of the EAS during
      fistulotomy limited to the lower two thirds of the EAS is associated with
      excellent continence and cure rates.

PMID- 22418883
TI  - Nonalcoholic fatty liver disease: pathologic patterns and biopsy evaluation in
      clinical research.
AB  - Nonalcoholic fatty liver disease (NAFLD) results in histologically complex
      specific and nonspecific injury patterns. In clinical research of NAFLD, the
      liver biopsy evaluation provides a wealth of information on the architectural
      arrangement and severity of a variety of histologic changes, including steatosis,
      inflammation, cellular injury, and fibrosis. This information is summarized as an
      overall diagnostic category, such steatosis or steatohepatitis and the severity
      of the injury can be graded and staged. Histopathologic disease classification in
      NAFLD is related to but separate from evaluation of individual histologic
      lesions. The patient population under study may affect the prevalence of
      histologic findings and in particular, pediatric patients with NAFLD may show a
      higher prevalence of zone 1 steatosis and periportal fibrosis as compared with
      adult populations. For the purposes of clinical research, it is important to
      provide the pathologist with biopsies that are adequate to classify the disease
      process as well as to grade and stage the changes. A current understanding of
      NAFLD pathologic classification, as well as nuances of grading and staging, is
      presented in this review.

PMID- 22418880
TI  - Stability of liver fibrosis among HCV-infected injection drug users.
AB  - BACKGROUND: There are few published data characterizing patterns of liver
      stiffness measurements (LSMs) among HCV-infected persons and their potential
      impact on clinical decisions (for example, deferring treatment and hepatocellular
      carcinoma surveillance). METHODS: A total of 591 HCV-infected injection drug
      users in a community-based cohort had four LSMs. We used semi-parametric latent
      class growth modelling to identify patterns, which then became a gold standard
      against which we characterized validity of information from the initial
      measurements. RESULTS: Median age was 49, 68% were male, 92% African-American and
      33% HIV-coinfected. The median LSM at visit 1 was 6.7 kPa (IQR 5.3-8.8). Over a
      median 1.75 years, LSM measures were stable; median change between visits was 0
      kPa (IQR -1.4-1.7). Only 3% had evidence of fibrosis progression. Other groups
      included stable patterns of no fibrosis (59%), moderate fibrosis (21%), severe
      fibrosis (7%) and cirrhosis (9%). Individuals with fibrosis progression were more
      likely to be HIV-infected than those with stable low fibrosis (P<0.001). The
      diagnostic accuracy of the first LSM for identification of need for cancer
      surveillance (cirrhosis >=12.3 kPa) was high (positive predictive value =97%).
      Although no single low LSM had high negative predictive value for significant
      fibrosis (metavir <2), individuals with two or more low results rarely had
      progression. CONCLUSIONS: These data underscore the stability of liver fibrosis
      in a cohort of predominantly African-American HCV-infected persons over 1.75
      years, support using LSMs to monitor untreated persons at risk for progression
      and assess need for hepatocellular carcinoma surveillance.

PMID- 22418884
TI  - NAFLD in the absence of metabolic syndrome: different epidemiology, pathogenetic
      mechanisms, risk factors for disease progression?
AB  - Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that have been
      associated with an increased risk of developing nonalcoholic fatty liver disease
      (NAFLD). Insulin resistance and central obesity are the key components of MetS,
      ultimately leading to liver fat accumulation and the subsequent development of
      necroinflammatory liver injury. However, the origin and nature of the metabolic
      stressors responsible for stimulating the progression of simple steatosis to
      nonalcoholic steatohepatitis (NASH) remain to be clearly identified. In addition,
      epidemiologic research on the association between MetS and NAFLD has provided
      only limited information to guide the development of targeted interventions, in
      particular, nutrition and pharmacologic prevention programs. This review
      summarizes the evidence supporting the proposal that NAFLD is not invariably
      associated with the presence of MetS, and mechanisms other than insulin
      resistance may contribute to the chronic inflammatory processes that underpin the
      development of liver fat accumulation and the subsequent architectural distortion
      of the liver. A special focus is given to increased hemoglobin as a risk factor
      for the development of NAFLD in the absence of MetS.

PMID- 22418885
TI  - Dyslipidemia in patients with nonalcoholic fatty liver disease.
AB  - Patients with nonalcoholic fatty liver disease (NAFLD) often have dyslipidemia
      along with other features of metabolic syndrome such as obesity, diabetes
      mellitus, and hypertension. The dyslipidemia in NAFLD is characterized by
      increased serum triglycerides, increased small, dense low-density lipoprotein
      (LDL nontype A) particles, and low high-density lipoprotein (HDL) cholesterol.
      The pathogenesis of dyslipidemia in NAFLD is not well understood, but it is
      likely related to hepatic overproduction of the very low-density lipoprotein
      particles and dysregulated clearance of lipoproteins from the circulation. There
      is unequivocal evidence that cardiovascular disease is the most common cause of
      mortality in patients with NAFLD. Aggressive treatment of dyslipidemia plays a
      critical role in the overall management of patients with NAFLD. Statins are the
      first-line agents to treat high cholesterol and their dosage should be adjusted
      based on achieving therapeutic targets and tolerability. Although all statins
      appear to be effective in improving cholesterol levels in patients with NAFLD,
      there is more experience with atorvastatin in patients with NAFLD; furthermore,
      it is the only statin to date to show a reduced cardiovascular morbidity in
      patients with NAFLD. The risk for serious liver injury from statins is quite rare
      and patients with NAFLD are not at increased risk for statin hepatotoxicity.
      Omega-3 fatty acids are perhaps the first choice to treat hypertriglyceridemia
      because of their safety, tolerability, and efficacy in improving serum
      triglycerides, as well as their potential to improve liver disease.

PMID- 22418886
TI  - Nonalcoholic steatohepatitis and noncirrhotic hepatocellular carcinoma: fertile
      soil.
AB  - Nonalcoholic fatty liver disease (NAFLD) is easily the most common cause of
      chronic liver disease in the United States (U.S.) as the hepatic manifestation of
      the metabolic syndrome. Although only 5 to 20% of patients with NAFLD are
      generally considered to meet criteria for nonalcoholic steatohepatitis (NASH),
      with its inherent risk for progression to cirrhosis, this still represents an
      alarmingly large number of individuals. The exponentially growing rates of
      hepatocellular carcinoma (HCC) in the U.S. may be partially attributable to
      increased numbers of NASH cirrhotics, although recent evidence has suggested that
      NAFLD may directly promote hepatic carcinogenesis independent of cirrhosis. This
      review focuses on HCC in noncirrhotic NASH with an emphasis on clinical
      presentation, pathogenesis, and implications for screening.

PMID- 22418887
TI  - Hypercoagulation and thrombophilia in nonalcoholic fatty liver disease:
      mechanisms, human evidence, therapeutic implications, and preventive
      implications.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a spectrum of disorders with a high
      prevalence in the industrialized world. Despite the high prevalence, the etiology
      and fundamental pathophysiology for the disease process is poorly understood.
      There is now a growing fund of knowledge suggesting that the ongoing inflammatory
      state associated with NAFLD leads to a low-level activation of the coagulation
      system. Although the data supporting this activation of the coagulation system
      are significant, the link with end-organ disease, mainly cardiovascular disease,
      is less firm and mostly epidemiological. In this review, we will explore the
      evidence for and against a hypercoagulable or thrombophilic state in NAFLD. We
      will examine possible pathophysiologic explanations and mechanisms, human
      epidemiologic and population-based data, and the possible therapeutic and
      preventative implications for treatment of thrombophilia in patients with this
      disease process.

PMID- 22418888
TI  - Obstructive sleep apnea-hypopnea syndrome and nonalcoholic fatty liver disease:
      emerging evidence and mechanisms.
AB  - Obstructive sleep apnea syndrome (OSAS) and nonalcoholic fatty liver disease
      (NAFLD) are common conditions, frequently encountered in patients with metabolic
      disorders. OSAS has been associated with an increased risk of cardiovascular and
      metabolic complications. It has been recently suggested that the chronic
      intermittent hypoxia of OSAS may also affect the presence and severity of NAFLD.
      We will critically review experimental and human evidence connecting OSAS to
      NAFLD pathogenesis, trying to dissect the effect of intermittent hypoxia from
      that of obesity and associated comorbidities, and examine molecular mechanisms
      connecting OSAS to liver and metabolic disease in NAFLD, including hypoxia
      inducible factor (HIF), nuclear factor-kappa B, unfolded protein response,
      hypoxic adipose tissue inflammation, and their therapeutic potential for NAFLD
      and its complications, including cirrhosis and hepatocellular carcinoma. Finally,
      we will provide suggestions for the management of NAFLD patients with suspected
      OSAS and recommendations for future research.

PMID- 22418889
TI  - Exercise and the liver: implications for therapy in fatty liver disorders.
AB  - The increasing recognition that fatty liver plays a direct role in the
      pathogenesis of cardiovascular and metabolic disease has resulted in significant
      research enquiry into the efficacy of lifestyle therapy in modulating liver fat.
      Recently, this has extended to the specific investigation of a possible
      independent benefit of physical activity/exercise in nonalcoholic fatty liver
      disease (NAFLD). In this article we review the effect of acute and regular
      exercise (training) on metabolism, including liver glucose and lipid metabolism,
      and the available human trials that have compared the benefit of regular exercise
      versus a nonexercise control on liver fat. The limited human research suggests
      that exercise can reduce liver fat and that this benefit may be mediated, in
      part, by a reduction in hepatic lipogenesis. The relative importance of
      extrahepatic adaptations and acute versus regular exercise in explaining this
      benefit are discussed. From a clinical perspective, the revelation of a benefit
      of exercise per se offers a novel approach for liver fat reduction, and
      highlights the importance of incorporating fitness assessment and prescription in
      the management of patients with fatty liver disorders. Implementation of exercise
      therapy in a clinical setting is arguably the biggest challenge because evidence
      shows that mere provision of information about the benefits of exercise and/or
      exercise prescription to the patient does not translate to positive outcomes.
      Rather, the focus should be on implementing strategies to promote behavior change
      including regular contact and assessment with a health care professional, self
      monitoring, and personalization of goals that focus on changing physical activity
      behavior.

PMID- 22418890
TI  - The impact of bariatric surgery on nonalcoholic steatohepatitis.
AB  - Nonalcoholic steatohepatitis (NASH) is a stage of nonalcoholic fatty liver
      disease (NAFLD), and in most patients, is associated with obesity and the
      metabolic syndrome. The current best treatment of NAFLD and NASH is weight
      reduction with the current options being life style modifications, with or
      without pharmaceuticals, and bariatric surgery. Bariatric surgery is an effective
      treatment option for individuals who are severely obese (body mass index >= 35
      kg/m(2)), and provides for long-term weight loss and resolution of obesity
      associated diseases in most patients. Regression and/or histologic improvement of
      NASH have been documented after bariatric surgery. We review the available
      literature reporting on the impact of the various bariatric surgery techniques on
      NASH.

PMID- 22418891
TI  - Late nonalcoholic fatty liver disease with cirrhosis: a pathologic case of lost
      or mistaken identity.
AB  - Late-stage nonalcoholic fatty liver disease (NAFLD) may present clinically and/or
      pathologically as cryptogenic cirrhosis. The subject of this report, a middle
      aged obese man with diabetes, underwent liver biopsy at the time of laparoscopic
      cholecystectomy because the liver surface appeared nodular and thickened. The
      biopsy showed relatively nondescript cirrhosis at initial low-power microscopic
      inspection, but glycogenated hepatocyte nuclei (consistent with diabetes), sparse
      macrovesicular fat, and very rare foci of residual mild steatohepatitis were
      later found. Slender fibrous septa (without significant inflammation and often
      enclosing microvessels) were present and interconnected to portal tracts.
      Immunostains for cytokeratin 7, ubiquitin, and glutamine synthetase provided
      additional histologic data supporting NAFLD as the cause of the cirrhosis in this
      case. A strategic pathologic approach is discussed, which can be utilized for the
      pathologic assessment of cirrhosis of unknown cause, particularly when late NAFLD
      is suspected.

PMID- 22418892
TI  - Testing for cervical cancer: new recommendations from the American Cancer
      Society, American Society for Colposcopy and Cervical Pathology, and American
      Society for Clinical Pathology.

PMID- 22418894
TI  - Inertial sensors in estimating walking speed and inclination: an evaluation of
      sensor error models.
AB  - With the increasing interest of using inertial measurement units (IMU) in human
      biomechanics studies, methods dealing with inertial sensor measurement errors
      become more and more important. Pre-test calibration and in-test error
      compensation are commonly used to minimize the sensor errors and improve the
      accuracy of the walking speed estimation results. However, the performance of a
      given sensor error compensation method does not only depend on the accuracy of
      the calibration or the sensor error evaluation, but also strongly relies on the
      selected sensor error model. The best performance could be achieved only when the
      essential components of sensor errors are included and compensated. Two new
      sensor error models, with the concerns about sensor acceleration measurement
      biases and sensor attachment misalignment, have been developed. The performance
      of these two error models were evaluated in the shank-mounted IMU-based walking
      speed/inclination estimation algorithm with a comparison of an existing error
      model. The treadmill walking experiment, conducted at both level and incline
      conditions, demonstrated the importance of sensor error model selection on the
      spatio-temporal gait parameter estimation performance. Accurate walking
      inclination estimation was made possible with a newly developed sensor error
      model.

PMID- 22418895
TI  - Haemodynamic forces on in vitro thrombi: a numerical analysis.
AB  - The flow of blood past an axisymmetric thrombus analogue, within an in vitro
      geometry, is computed via solution of the discrete three-dimensional (3D) Navier
      Stokes equations. Particle tracking is used to model the behaviour of
      thrombocytes (platelets) moving throughout the domain and to investigate
      behaviour with respect to the platelets. The system is explored using shear rate
      to quantify the effects an idealised thrombus has with respect to an undisturbed
      in vitro geometry over 'Poiseuille flow' shear rate conditions applicable to in
      vivo and in vitro experiments (1,200-10,000 s-1). Local shear rate variations
      show peaks in shear rate greater than double that of Poiseuille flow conditions.
      These local shear rate variations are observed to be non-linear, despite the low
      Reynolds number (5.2-43.4) within the system. Topological transitions of shear
      rate are observed, limiting the height of peak shear rate within the system,
      suggesting a thrombus growth limiting behaviour. Temporal gradients of shear
      rate, measured with respect to individual platelets, were calculated. Multiple
      regions of peak shear rate gradient were observed throughout the flow, suggesting
      that platelet-platelet interaction may not be limited to regions near to the
      surface of the thrombus.

PMID- 22418893
TI  - Isoprenoids and related pharmacological interventions: potential application in
      Alzheimer's disease.
AB  - Two major isoprenoids, farnesyl pyrophosphate and geranylgeranyl pyrophosphate,
      serve as lipid donors for the posttranslational modification (known as
      prenylation) of proteins that possess a characteristic C-terminal motif. The
      prenylation reaction is catalyzed by prenyltransferases. The lipid prenyl group
      facilitates to anchor the proteins in cell membranes and mediates protein-protein
      interactions. A variety of important intracellular proteins undergo prenylation,
      including almost all members of small GTPase superfamilies as well as
      heterotrimeric G protein subunits and nuclear lamins. These prenylated proteins
      are involved in regulating a wide range of cellular processes and functions, such
      as cell growth, differentiation, cytoskeletal organization, and vesicle
      trafficking. Prenylated proteins are also implicated in the pathogenesis of
      different types of diseases. Consequently, isoprenoids and/or prenyltransferases
      have emerged as attractive therapeutic targets for combating various disorders.
      This review attempts to summarize the pharmacological agents currently available
      or under development that control isoprenoid availability and/or the process of
      prenylation, mainly focusing on statins, bisphosphonates, and prenyltransferase
      inhibitors. Whereas statins and bisphosphonates deplete the production of
      isoprenoids by inhibiting the activity of upstream enzymes, prenyltransferase
      inhibitors directly block the prenylation of proteins. As the importance of
      isoprenoids and prenylated proteins in health and disease continues to emerge,
      the therapeutic potential of these pharmacological agents has expanded across
      multiple disciplines. This review mainly discusses their potential application in
      Alzheimer's disease.

PMID- 22418897
TI  - Substrate considerations for graphene synthesis on thin copper films.
AB  - Chemical vapor deposition on copper substrates is a primary technique for
      synthesis of high quality graphene films over large areas. While well-developed
      processes are in place for catalytic growth of graphene on bulk copper
      substrates, chemical vapor deposition of graphene on thin films could provide a
      means for simplified device processing through the elimination of the layer
      transfer process. Recently, it was demonstrated that transfer-free growth and
      processing is possible on SiO(2). However, the Cu/SiO(2)/Si material system must
      be stable at high temperatures for high quality transfer-free graphene. This
      study identifies the presence of interdiffusion at the Cu/SiO(2) interface and
      investigates the influence of metal (Ni, Cr, W) and insulating (Si(3)N(4),
      Al(2)O(3), HfO(2)) diffusion barrier layers on Cu-SiO(2) interdiffusion, as well
      as graphene structural quality. Regardless of barrier choice, we find the
      presence of Cu diffusion into the silicon substrate as well as the presence of Cu
      Si-O domains on the surface of the copper film. As a result, we investigate the
      choice of a sapphire substrate and present evidence that it is a robust substrate
      for synthesis and processing of high quality, transfer-free graphene.

PMID- 22418896
TI  - Ten ways to improve the use of statistical mediation analysis in the practice of
      child and adolescent treatment research.
AB  - Despite guidelines and repeated calls from the literature, statistical mediation
      analysis in youth treatment outcome research is rare. Even more concerning is
      that many studies that have reported mediation analyses do not fulfill basic
      requirements for mediation analysis, providing inconclusive data and clinical
      implications. As a result, after more than five decades of research, it is still
      largely unknown through which processes youth treatment works and what the
      effective treatment components are. In this article, we present ten ways in which
      the use of statistical mediation analysis in youth treatment outcome research may
      be improved. These ten ways are related both to conceptual and methodological
      issues. In discussing how youth clinical researchers may optimally implement
      these directions, we argue that studies should employ the strongest research
      designs possible. In so doing, we describe different levels of a mediation
      evidence ladder. Studies on each step of the ladder contribute to an
      understanding of mediation processes, but the strongest evidence for mediation is
      provided by studies that can be classified at the highest level. With the help of
      the ladder of mediation evidence, results from youth mediation treatment outcome
      research can be evaluated on their scientific as well as clinical impact.

PMID- 22418898
TI  - Bipolar electrochemistry for cargo-lifting in fluid channels.
AB  - We report for the first time the vertical propulsion of conducting beads in
      liquid filled capillaries by bipolar electrochemistry. The beads, when exposed to
      an external electric field, act as bipolar electrodes showing hydroquinone
      oxidation on one side and proton reduction on the other side. The related
      asymmetric bubble generation occurring at the bottom part of the beads drives
      their motion. The characteristic features of the propulsion can be tuned by
      changing parameters such as the applied electric field or the capillary shape.
      Using a conical capillary, we show that a Yo-Yo type motion can be induced. The
      quite versatile concept can then be used for cargo-lifting and is of potential
      interest for microfluidic applications in LOC devices.

PMID- 22418899
TI  - What should be learnt about the management of obstructive sleep apnea in
      hypertension?

PMID- 22418900
TI  - Is there room for dual blockade of the renin-angiotensin-aldosterone system?

PMID- 22418901
TI  - Insulin-endothelial interactions:  discovering the participation of
      neuroadrenergic influences.

PMID- 22418902
TI  - Reservations on the reservoir.

PMID- 22418903
TI  - Low-grade inflammation and arterial stiffness in the elderly.

PMID- 22418904
TI  - Do microvascular retinal changes improve cardiovascular risk estimation?

PMID- 22418905
TI  - The importance of myocardial fibrosis in hypertensive heart disease.

PMID- 22418906
TI  - The key role of microvascular structure assessment in treated hypertensive
      patients.

PMID- 22418907
TI  - The kaliuretic impact of cicletanine compared to hydrochlorothiazide.

PMID- 22418908
TI  - Prevention of microalbuminuria in patients with type 2 diabetes and hypertension.
AB  - BACKGROUND: We have previously demonstrated in the Randomized Olmesartan and
      Diabetes Microalbuminuria Prevention study that the angiotensin receptor blocker
      (ARB) olmesartan delays the onset of microalbuminuria in patients with type 2
      diabetes. Now, we investigated the effect in the subpopulation with hypertension.
      METHODS: Overall, 4020 patients with type 2 diabetes and hypertension at baseline
      (defined by a SBP/DBP >=130/80 mmHg or use of antihypertensive medication)
      received either 40 mg olmesartan once daily or placebo for a median of 3.2 years
      in a randomized, double-blind, multicenter, controlled trial. Additional
      antihypertensive drugs (except angiotensin-converting enzyme inhibitors or ARBs)
      were used as needed to lower blood pressure (BP) to less than 130/80 mmHg.
      RESULTS: The average BP was 126.3/74.7 and 129.5/76.6 mmHg, respectively (P <
      0.001). Olmesartan delayed the time to onset of microalbuminuria by 25% (hazard
      ratio = 0.75; 95% confidence interval = 0.61-0.92, P = 0.007). Patients with a
      baseline SBP above the median of 136.7 mmHg and a SBP reduction above the median
      of 17.45 mmHg had a lower incidence of microalbuminuria than patients with a SBP
      reduction of less than 17.45 (8.1 vs. 11.2%, P < 0.0001). Independent from the
      baseline BP and the degree of BP reduction a 15-39% increase in the time to onset
      of microalbuminuria was detectable by olmesartan treatment. Cardiovascular events
      were comparable and occurred in 93 (4.6%) patients taking olmesartan and 86
      (4.4%) taking placebo. CONCLUSION: Patients with a better BP reduction are less
      likely to develop microalbuminuria. Treatment with olmesartan delayed the onset
      of microalbuminuria independent of the baseline BP and the degree of BP
      reduction.

PMID- 22418909
TI  - Blood pressure variation with cuff height:  effect of time.

PMID- 22418911
TI  - Tracking the better ultrasound protocols to measure carotid intima-media
      thickness.

PMID- 22418913
TI  - Management of hypertension after kidney transplantation:  a possible role for
      spironolactone?

PMID- 22418915
TI  - Hypertension after kidney transplantation:  calcineurin inhibitors increase salt
      sensitivity.

PMID- 22418918
TI  - Association of central and peripheral pulse pressure with intermediate
      cardiovascular phenotypes.

PMID- 22418920
TI  - [Psychiatrists as refugees in Palestine: 1933-1945].
AB  - The paper discusses the migration of German Jewish psychiatrists from Nazi
      Germany to Palestine during the 1930s. It focuses on their special assimilation
      process as immigrants who belonged to a culture different from the dominant
      Eastern European socialist Zionism and as a professional group which belonged to
      a marginalized discipline.

PMID- 22418921
TI  - 177Lu-DO3A-HSA-Z EGFR:1907: characterization as a potential radiopharmaceutical
      for radionuclide therapy of EGFR-expressing head and neck carcinomas.
AB  - Epidermal growth factor receptor 1 (EGFR) is an attractive target for
      radionuclide therapy of head and neck carcinomas. Affibody molecules against EGFR
      (Z(EGFR)) show excellent tumor localizations in imaging studies. However, one
      major drawback is that radiometal-labeled Affibody molecules display extremely
      high uptakes in the radiosensitive kidneys which may impact their use as
      radiotherapeutic agents. The purpose of this study is to further explore whether
      radiometal-labeled human serum albumin (HSA)-Z(EFGR) bioconjugates display
      desirable profiles for the use in radionuclide therapy of EGFR-positive head and
      neck carcinomas. The Z(EFGR) analog, Ac-Cys-Z(EGFR:1907), was site-specifically
      conjugated with HSA. The resulting bioconjugate 1,4,7,10-tetraazacyclododecane
      1,4,7-triacetic acid (DO3A)-HSA-Z(EGFR:1907) was then radiolabeled with either
      (64)Cu or (177)Lu and subjected to in vitro cell uptake and internalization
      studies using the human oral squamous carcinoma cell line SAS. Positron emission
      tomography (PET), single photon emission computed tomography (SPECT), and
      biodistribution studies were conducted using SAS-tumor-bearing mice. Cell studies
      revealed a high (8.43 +/- 0.55 % at 4 h) and specific (0.95 +/- 0.09 % at 4 h)
      uptake of (177)Lu-DO3A-HSA-Z(EGFR:1907) as determined by blocking with
      nonradioactive Z(EGFR:1907). The internalization of (177)Lu-DO3A-HSA-Z(EGFR:1907)
      was verified in vitro and found to be significantly higher than that of (177)Lu
      labeled Z(EFGR) at 2-24 h of incubation. PET and SPECT studies showed good tumor
      imaging contrasts. The biodistribution of (177)Lu-DO3A-HSA-Z(EGFR:1907) in SAS
      tumor-bearing mice displayed high tumor uptake (5.1 +/- 0.44 % ID/g) and liver
      uptake (31.5 +/- 7.66 % ID/g) and moderate kidney uptake (8.5 +/- 1.08 % ID/g) at
      72 h after injection. (177)Lu-DO3A-HSA-Z(EGFR:1907) shows promising in vivo
      profiles and may be a potential radiopharmaceutical for radionuclide therapy of
      EGFR-expressing head and neck carcinomas.

PMID- 22418924
TI  - Variation in antioxidant attributes at three ripening stages of guava (Psidium
      guajava L.) fruit from different geographical regions of Pakistan.
AB  - The present investigation was carried out to appraise the levels of total phenols
      and vitamin C as well as antioxidant potential at three different ripening stages
      (un-ripe, semi-ripe and fully-ripe) of guava (Psidium guajava L.) fruit collected
      from three different geographical regions of Pakistan (Islamabad, Faisalabad and
      Bhakkar). The antioxidant potential of guava fruit extracts was assessed by means
      of different in-vitro antioxidant assays, namely inhibition of peroxidation in
      linoleic acid system, reducing power and radical scavenging capability. Overall,
      fruit at the un-ripe stage (G1) exhibited the highest levels of TPC, TFC,
      reducing power and DPPH radical scavenging activity, followed by the semi-ripe
      (G2) and fully-ripe (G3) stages. On the other hand, vitamin C content increased
      as the fruit maturity progressed, with highest value seen at the fully-ripe stage
      (G3) followed by the semi-ripe (G2) and un-ripe stage (G1). The concentration of
      vitamin C in fruits varied as: Faisalabad (136.4-247.9 mg 100 g-1), Islamabad
      (89.7-149.7 mg 100 g-1) and Bhakkar (73.1-129.5 mg 100 g-1). The results showed
      that different stages of maturation and geographical locations had profound
      effects on the antioxidant activity and vitamin C contents of guava fruit.

PMID- 22418922
TI  - Inhibition of STAT3 signaling prevents vascular smooth muscle cell proliferation
      and neointima formation.
AB  - Dedifferentiation, migration, and proliferation of resident vascular smooth
      muscle cells (SMCs) are key components of neointima formation after vascular
      injury. Activation of signal transducer and activator of transcription-3 (STAT3)
      is suggested to be critically involved in this process, but the complex
      regulation of STAT3-dependent genes and the functional significance of inhibiting
      this pathway during the development of vascular proliferative diseases remain
      elusive. In this study, we demonstrate that STAT3 was activated in neointimal
      lesions following wire-induced injury in mice. Phosphorylation of STAT3 induced
      trans-activation of cyclin D1 and survivin in SMCs in vitro and in neointimal
      cells in vivo, thus promoting proliferation and migration of SMCs as well as
      reducing apoptotic cell death. WP1066, a highly potent inhibitor of STAT3
      signaling, abrogated phosphorylation of STAT3 and dose-dependently inhibited the
      functional effects of activated STAT3 in stimulated SMCs. The local application
      of WP1066 via a thermosensitive pluronic F-127 gel around the dilated arteries
      significantly inhibited proliferation of neointimal cells and decreased the
      neointimal lesion size at 3 weeks after injury. Even though WP1066 application
      attenuated the injury-induced up-regulation of the chemokine RANTES at 6 h after
      injury, there was no significant effect on the accumulation of circulating cells
      at 1 week after injury. In conclusion, these data identify STAT3 as a key
      molecule for the proliferative response of SMC and neointima formation. Moreover,
      inhibition of STAT3 by the potent and specific compound WP1066 might represent a
      novel and attractive approach for the local treatment of vascular proliferative
      diseases.

PMID- 22418925
TI  - Facile synthesis and herbicidal evaluation of 4H-3,1-benzoxazin-4-ones and 3H
      quinazolin-4-ones with 2-phenoxymethyl substituents.
AB  - Series of 4H-3,1-benzoxazin-4-ones and 3H-quinazolin-4-ones with phenoxy-methyl
      substituents were rationally designed and easily synthesized via one-pot N
      acylation/ring closure reactions of anthranilic acids with 2-phenoxyacetyl
      chlorides to yield the 4H-3,1-benzoxazin-4-ones, and subsequently substituted
      with amino derivatives to obtain the 3H-quinazolin-4-ones. The herbicidal
      evaluation was performed on the model plants barnyard grass (a monocotyledon) and
      rape (a dicotyledon), and most of the title compounds displayed high levels of
      phytotoxicity. The active substructure and inhibitory phenotype analysis
      indicated that these compounds could be attributed to the class of plant hormone
      inhibitors. A docking study of several representative compounds with the hormone
      receptor TIR1 revealed an appreciable conformational match in the active site,
      implicating these compounds are potential lead hits targeting this receptor.

PMID- 22418926
TI  - Cancer chemoprevention by carotenoids.
AB  - Carotenoids are natural fat-soluble pigments that provide bright coloration to
      plants and animals. Dietary intake of carotenoids is inversely associated with
      the risk of a variety of cancers in different tissues. Preclinical studies have
      shown that some carotenoids have potent antitumor effects both in vitro and in
      vivo, suggesting potential preventive and/or therapeutic roles for the compounds.
      Since chemoprevention is one of the most important strategies in the control of
      cancer development, molecular mechanism-based cancer chemoprevention using
      carotenoids seems to be an attractive approach. Various carotenoids, such as beta
      carotene, a-carotene, lycopene, lutein, zeaxanthin, beta-cryptoxanthin,
      fucoxanthin, canthaxanthin and astaxanthin, have been proven to have anti
      carcinogenic activity in several tissues, although high doses of beta-carotene
      failed to exhibit chemopreventive activity in clinical trials. In this review,
      cancer prevention using carotenoids are reviewed and the possible mechanisms of
      action are described.

PMID- 22418927
TI  - Biodegradability and biocompatibility study of poly(chitosan-g-lactic acid)
      scaffolds.
AB  - A biodegradable, biocompatible poly(chitosan-g-lactic acid) (PCLA) scaffold was
      prepared and evaluated in vitro and in vivo. The PCLA scaffold was obtained by
      grafting lactic acid (LA) onto the amino groups on chitosan (CS) without a
      catalyst. The PCLA scaffolds were characterized by Fourier Transform infrared
      spectroscopy (FT-IR) and scanning electron microscopy (SEM). The biodegradabilty
      was determined by mass loss in vitro, and degradation in vivo as a function of
      feed ratio of LA/CS. Bone marrow mesenchymal stem cell (BMSC) culture experiments
      and histological examination were performed to evaluate the PCLA scaffolds'
      biocompatibility. The results indicated that PCLA was promising for tissue
      engineering application.

PMID- 22418928
TI  - Spectral properties of substituted coumarins in solution and polymer matrices.
AB  - The absorption and fluorescence spectra of substituted coumarins (2-oxo-2H
      chromenes) were investigated in solvents and in polymer matrices. The
      substitutions involved were: (1) by groups with varying electron donating ability
      such as CH3, OCH3 and N(CH3)2, mainly, but not exclusively, in positions 7 and
      (2), by either CHO or 4-PhNHCONHN=CH- in position 3. While the spectra of non
      substituted coumarin-3-carbaldehyde has absorptions at approximately 305 and 350
      nm, substitution at position 7 leads to remarkable changes in the shape of the
      absorption spectrum and shifts the absorption to a longer wavelength. Similarly,
      the replacement of the formyl group with a semicarbazide group substantially
      influences the shape of the absorption spectrum, and coumarins which have only
      N(CH3)2 in position 7 experience small changes. These changes are associated with
      the increasing intramolecular charge transfer (ICT) character and increasing
      conjugation length of the chromophoric system, respectively, in the studied
      molecules. The fluorescence is almost negligible for derivatives which have H in
      this position. With increasing electron donating ability, and the possibility of
      a positive mesomeric (+M) effect of the substituent in position 7 of the coumarin
      moiety, the fluorescence increases, and this increase is most intense when
      N(CH3)2 substitutes in this position, for both 3-substituted derivatives.
      Spectral measurements of the studied coumarins in polymer matrices revealed that
      the absorption and fluorescence maxima lay within the maxima for solvents, and
      that coumarins yield more intense fluorescence in polymer matrices than when they
      are in solution. The quantum yield of derivatives which have a dimethylamino
      group in position 7 in polymer matrices approaches 1, and the fluorescence
      lifetime is within the range of 0.5-4 ns. The high quantum yield of 7
      dimethylamino derivatives qualifies them as laser dyes which have k(F) higher
      than k(nr) in the given medium. This is caused by stiffening of the coumarin
      structure in polar polymer matrices, such as PMMA and PVC, due to higher micro
      viscosity than in solution and intermolecular dipole-dipole interaction between
      chromophore (dopant) and matrix.

PMID- 22418929
TI  - Antinociceptive and anti-inflammatory effects of a lectin-like substance from
      Clitoria fairchildiana R. Howard seeds.
AB  - Lectins are proteins that have the ability to bind specifically and reversibly to
      carbohydrates and glycoconjugates, without altering the structure of the glycosyl
      ligand. They are found in organisms such as viruses, plants and humans, and they
      have been shown to possess important biological activities. The objective of this
      study was to purify and characterize lectins in the seeds of Clitoria
      fairchildiana, as well as to verify their biological activities. The results
      indicated the presence of a lectin (CFAL) in the glutelin acid protein fraction,
      which agglutinated native rabbit erythrocytes. CFAL was purified by column
      chromatography ion-exchange, DEAE-Sephacel, which was obtained from a peak of
      protein retained in the matrix by applying 0.5 M NaCl using the step-wise method.
      Electrophoretic analysis of this lectin in SDS-PAGE indicated a two band pattern
      protein molecular mass of approximately 100 and 116 kDa. CFAL proved to be
      unspecific to all carbohydrates/glycoconjugates in common use for the sugar
      inhibition test. This lectin showed no significant cytotoxicity to human red
      blood cells. It was observed that CFAL has anti-inflammatory activity in the paw
      edema induced by carrageenan model, in which a 64% diminution in edema was
      observed. Antinociceptive effects were observed for CFAL in the abdominal
      writhing test (induced by acetic acid), in which increasing doses of the lectin
      caused reduction in the number of contortions by up to 72%. It was concluded that
      the purified and characterized lectin from the seeds of Clitoria fairchildiana
      has anti-inflammatory and antinociceptive activity, and is not cytotoxic to human
      erythrocytes.

PMID- 22418930
TI  - Antiproliferative, antimicrobial and apoptosis inducing effects of compounds
      isolated from Inula viscosa.
AB  - The antiproliferative and antimicrobial effects of thirteen compounds isolated
      from Inula viscosa (L.) were tested in this study. The antiproliferative activity
      was tested against three cell lines using the MTT assay. The microdilution method
      was used to study the antimicrobial activity against two Gram positive bacteria,
      two Gram negative bacteria and one fungus. The apoptotic activity was determined
      using a TUNEL colorimetric assay. Scanning electron microscopy was used to study
      the morphological changes in treated cancer cells and bacteria. Antiproliferative
      activity was observed in four flavonoids (nepetin, 3,3'-di-O-methylquercetin,
      hispidulin, and 3-O-methylquercetin). 3,3'-di-O-Methylquercetin and 3-O
      methylquercetin showed selective antiproliferative activity against MCF-7 cells,
      with IC(50) values of 10.11 and 11.23 ug/mL, respectively. Both compounds exert
      their antiproliferative effect by inducing apoptosis as indicted by the presence
      of DNA fragmentation, nuclear condensation, and formation of apoptotic bodies in
      treated cancer cells. The antimicrobial effect of Inula viscosa were also noticed
      in 3,3'-di-O-methylquercetin and 3-O-methyquercetin that inhibited Bacillus
      cereus at MIC of 62.5 and 125 ug/mL, respectively. Salmonella typhimurium was
      inhibited by both compounds at MIC of 125 ug/mL. 3,3'-di-O-Methylquercetin
      induced damage in bacterial cell walls and cytoplasmic membranes. Methylated
      quercetins isolated from Inula viscosa have improved anticancer and antimicrobial
      properties compared with other flavonoids and are promising as potential
      anticancer and antimicrobial agents.

PMID- 22418931
TI  - Phenolic concentrations and antioxidant properties of wines made from north
      american grapes grown in china.
AB  - The characteristics of wine phenolics found in several North American and (for
      comparison) European grape cultivars grown in China were analyzed. This was done
      to find non-Vitis vinifera wines with prominent features in order to diversify
      the kinds of wines. The phenolic richness and antioxidant activity decreased in
      the order: red > rose > white wines. In the red wines, the American grape
      'Cynthiana' had the highest total concentrations of phenols, anthocyanins,
      flavonols and phenolic acids, as well as antioxidant capacity, followed by the
      French hybrid 'Chambourcin', the lowest were detected in two European grape
      varieties, 'Merlot' and 'Cabernet Sauvignon', while the total flavon-3-ols levels
      were reversed among these red grape cultivars. The highest concentration of
      stilbenes out of all the wines analyzed was found in the 'Merlot' variety. There
      were significant differences among wine phenolic compositions between North
      American and European grape cultivars. The antioxidant activities were
      significantly related to the concentrations of total phenols (r2 = 0.996),
      anthocyanins (r2 = 0.984), flavonols (r2 = 0.850) and gallic acid (r2 = 0.797).
      The prominent features of wine aroma and nutrition could make the American grape
      wines attractive to consumers. It is therefore necessary to perform further
      research on cultural practices and wine making involving these grapes.

PMID- 22418932
TI  - Phytoecdysteroids from the roots of Achyranthes bidentata Blume.
AB  - Two new phytoecdysteroids, (25S)-20,22-O-(R-ethylidene)inokosterone and 20,22-O
      (R-3-methoxycarbonyl)propylidene-20-hydroxyecdysone, together with six known
      phytoecdysteroids 3-8 were isolated from the roots of Achyranthes bidentata
      Blume. The new structures were established on the basis of spectroscopic studies
      and chemical evidences. The absolute configuration at C-25 in the structure of
      known compound 3 was determined by chemical and spectroscopic means.

PMID- 22418933
TI  - Salvianolic acid A inhibits PDGF-BB induced vascular smooth muscle cell migration
      and proliferation while does not constrain endothelial cell proliferation and
      nitric oxide biosynthesis.
AB  - Proliferation and migration of vascular smooth muscle cells (VSMCs) are critical
      events in the initiation and development of restenosis upon percutaneous
      transluminal coronary angioplasty (PTCA). Polyphenols have been suggested to
      ameliorate post-angioplasty restenosis. Salvianolic A (SalA) is one of the most
      abundant polyphenols extracted from salvia. In this study, we investigated the
      effect of salvianolic A (SalA) on the migration and proliferation of VSMCs. We
      found a preferential interaction of SalA with cellular systems that rely on the
      PDGF signal, but not on the EGF and bFGF signal. SalA inhibits PDGF-BB induced
      VSMC proliferation and migration in the concentration range from 0.01 to 0.1 MUM.
      The inhibition of SalA on VSMC proliferation is associated with cell cycle
      arrest. We also found that SalA inhibits the PDGFRbeta-ERK1/2 signaling cascade
      activated by PDGF-BB in VSMCs. In addition, SalA does not influence the
      proliferation of endothelial cells, the synthesis of NO and eNOS protein
      expression. Our results suggest that SalA inhibits migration and proliferation of
      VSMCs induced by PDGF-BB via the inhibition of the PDGFRbeta-ERK1/2 cascade, but
      that it does not constrain endothelial cell proliferation and nitric oxide
      biosynthesis. Thus, the present study suggests a novel adjunct pharmacological
      strategy to prevent angioplasty-related restenosis.

PMID- 22418938
TI  - An itchy mouse: a potential model of atopic dermatitis.

PMID- 22418934
TI  - phenix.mr_rosetta: molecular replacement and model rebuilding with Phenix and
      Rosetta.
AB  - The combination of algorithms from the structure-modeling field with those of
      crystallographic structure determination can broaden the range of templates that
      are useful for structure determination by the method of molecular replacement.
      Automated tools in phenix.mr_rosetta simplify the application of these combined
      approaches by integrating Phenix crystallographic algorithms and Rosetta
      structure-modeling algorithms and by systematically generating and evaluating
      models with a combination of these methods. The phenix.mr_rosetta algorithms can
      be used to automatically determine challenging structures. The approaches used in
      phenix.mr_rosetta are described along with examples that show roles that
      structure-modeling can play in molecular replacement.

PMID- 22418939
TI  - Report on the 6th World Congress of Itch.

PMID- 22418940
TI  - Mediator1: an important intermediary of vitamin D receptor-regulated epidermal
      function and hair follicle biology.
AB  - Considerable data in the literature support the idea that 1,25-dihydroxyvitamin
      D3 and the vitamin D receptor (VDR) are involved in regulating skin biology.
      Studies using cultured keratinocytes, artificial human skin, and transgenic mouse
      models, as well as observations in patients with rickets, provide evidence of
      this pathway's importance in epidermal proliferation and differentiation and the
      hair growth cycle. The report by Oda et al. in this issue also indicates an
      important role of the VDR coactivator mediator 1 in these processes.

PMID- 22418941
TI  - Homeward bound: how do skin dendritic cells find their way into the lymph system?
AB  - The success of the adaptive immune system relies upon the transport of antigens
      by dendritic cells (DCs) from skin via lymphatic vessels to lymph nodes where DCs
      present antigen to T cells. Little is known about the requirements for so-called
      "reverse transmigration" (RT). Torzicky et al. in this issue demonstrate that
      CD31, CD99, and CXCR4 play key roles in RT, suggesting that adhesion occurs in a
      defined sequence during the passage of DC into lymphatics.

PMID- 22418942
TI  - Demonstration of melanosome transfer by a shedding microvesicle mechanism.
AB  - The process of melanosome transfer has fascinated pigment cell biologists for
      decades. Whole-organelle transfer is a unique property of melanocytes, suggesting
      that the biologic underpinnings of the process reflect melanocyte- and
      keratinocyte-specific proteins and pathways. Although several mechanisms of
      melanosome transfer are likely to occur in the skin, Ando et al. focused on a new
      mechanism of melanosome transfer that involves release of melanosome-containing
      globules, similar to shedding vesicles into the extracellular space, followed by
      uptake by keratinocytes. This model adds further complexity to the process of
      melanosome transfer in the skin.

PMID- 22418943
TI  - Nondimensional scaling laws for controlling pharmaceutical spray uniformity:
      understanding and scale-up.
AB  - Spatially resolved drop size, drop velocity, and spray volume flux measurements
      for sprays produced by a commonly used pharmaceutical coating nozzle were
      performed in this study. Results showed three distinctive spray patterns:
      Gaussian, homogeneous, and dumbbell shaped. We found that transition from a
      dumbbell-shaped to a homogeneous pattern is related to the shaping air-induced
      breakup of already formed drops: depending on the drop size upstream of the
      location where the shaping air flows meet (i.e., the "junction" point), the drop
      viscosity, and the magnitude of the shaping air velocity, the shaping air can
      either pinch the spray or cause additional drop breakup. When the former
      outweighs the latter, the dumbbell-shaped pattern occurs; the homogeneous pattern
      is present when the opposite occurs. A corollary to this experimental
      interpretation is that whether additional drop breakup homogenizes the sprays or
      pinches, it is related to a Weber number (We) that is calculated using drop sizes
      upstream of the junction point, drop viscosity and surface tension, and the
      shaping air velocity at the junction point. With this idea in mind, we propose a
      We-based scaling method for optimizing the uniformity of air-assist spray
      patterns.

PMID- 22418944
TI  - [Sport injuries and overuse damage of the elbow].
AB  - Sports injuries of the elbow joint can be acute or can arise due to chronic
      overuse. Such overstress syndromes are common in overhead, throwing and racket
      sports activities. The present article introduces diagnostic algorithms developed
      from knowledge gained through motion analysis, clinical examination and further
      imaging. The diagnosis of the overtaxing syndromes mainly depends on these
      findings. Basically most of the disorders in the elbow joint can be treated
      conservatively. If this is not the case or if the conservative treatment does not
      succeed, arthroscopic techniques, ligament reconstruction or nerve decompression
      are the major alternatives. The prognosis for regaining elbow function and
      returning to the previous level of performance is generally good. The resulting
      therapy recommendations are summarised on the basis of the current highest grades
      of evidence.

PMID- 22418945
TI  - The contribution of children's temperamental fear and effortful control to
      restraint and seclusion during inpatient treatment in a psychiatric hospital.
AB  - The current study examined temperament characteristics as risk factors for
      restraint and seclusion (R/S) events in psychiatrically hospitalized youth,
      extending work that has sought to identify R/S risk factors and research
      examining temperament-behavior problem associations that has largely relied upon
      community samples. It was anticipated that children with poor effortful control
      (EC) and greater frustration would have more instances of R/S during psychiatric
      hospitalization. The contribution of children's fearfulness to R/S was also
      examined. A measure of temperament was completed by youths' clinicians and youths
      (n = 52) completed objective measures of EC. The frequency of R/S events for each
      participant was obtained from hospital records. After controlling for R/S risk
      factors, lower EC and higher fearfulness predicted increased R/S occurrences
      during the first 2 weeks of hospitalization and over the course of children's
      entire hospitalization. These findings indicate that temperament should
      potentially be considered in individualized treatment plans targeting the
      prevention and/or reduction of R/S. Additional implications of the findings are
      also discussed.

PMID- 22418946
TI  - Effects of the blended fibroin/aloe gel film on wound healing in streptozotocin
      induced diabetic rats.
AB  - Delayed healing remains a major clinical problem and here we have sought to
      develop an improved dressing film comprising 1.95% w/v fibroin and 0.05% w/v aloe
      gel extract. The tensile strength of dry film was 21.1 +/- 0.5 MPa and broke at
      1.1 +/- 0.2% elongation; corresponding values for wet film were 18.3 +/- 1.3 MPa
      and 1.9 +/- 0.1%. The film maintained its shape upon water immersion and the
      swelling ratio of the dry film was 0.8 +/- 0.1 while the water uptake was 43.7 +/
      2.6%. After 28 days of incubation in phosphate buffered saline (1 M, pH 7.4, 37 
      degrees C), the weight of film was reduced by 6.7 +/- 1.1% and the tensile
      strength and elongation at breaking point (dry state) were 15.4 +/- 0.6 MPa and
      1.5 +/- 0.2%, respectively. Compared to aloe-free fibroin film (2.0% fibroin
      extract only), the blended film enhanced the attachment and proliferation of skin
      fibroblasts. The bFGF immunofluorescence of fibroblasts cultured on the blended
      film appeared greater than those cultured on tissue culture plate or on aloe-free
      fibroin film while alpha-smooth muscle actin was maintained. In streptozotocin
      induced diabetic rats, the wounds dressed with the blended film were smaller (p
      <0.05) by day 7 after wounding, compared to untreated diabetic wounds. Histology
      of repaired diabetic wounds showed the fibroblast distribution and collagen fiber
      organization to be similar to wounds in normal rats, and this was matched by
      enhanced hydroxyproline content. Thus, such accelerated wound healing by the
      blended fibroin/aloe gel films may find application in treatment of diabetic non
      healing skin ulcers.

PMID- 22418947
TI  - Congenital chylous ascites and lymphedema in Down's syndrome.

PMID- 22418948
TI  - Inborn errors of metabolism in the neonatal period - is it time to change our
      practice?

PMID- 22418950
TI  - Further evidence for the role of IP 3R 1 in regulating subsynaptic gene
      expression and neuromuscular transmission.
AB  - The inositol 1,4,5-triphosphate IP 3R channel is highly expressed on specialized
      ER membrane, where it initiates a slow wave of Ca ( 2+) release from internal
      stores, allowing subcellular compartmentalization of Ca ( 2+) signals. In
      skeletal muscle, IP 3R 1 is also highly concentrated at some myonuclei,
      particularly near the NMJ. We have reported that in fully developed adult muscle,
      IP 3R 1 knockdown by siRNA increases synaptic strength at both pre- and post
      synaptic sites of neuromuscular transmission, increasing both the amplitude and
      frequency of spontaneous quantal events and quantal content, as well as
      expression of AChR subunits and other NMJ-specific genes. Here, we demonstrate
      that reducing IP 3R 1 activity in mouse TA muscle by promoting hydrolysis locally
      of IP 3R 1 also amplifies expression of subsynaptic genes and transcription
      factors. Furthermore, using a retrograde tracer, cholera toxin B subunit, we find
      that siRNA-mediated silencing of IP 3R 1 in TA muscle increases vesicle
      trafficking. These studies suggest that postsynaptic IP 3R 1 activity regulates
      synaptic gene expression and neuromuscular transmission.

PMID- 22418951
TI  - Can anomalies of fetal brain circulation be useful in the management of growth
      restricted fetuses?
AB  - Assessment of the fetal cerebral circulation provides important information on
      the hemodynamic changes associated with chronic hypoxia and intrauterine growth
      restriction. Despite the incorporation of new US parameters, the landmark for the
      fetal brain hemodynamic evaluation is still the middle cerebral artery. However,
      new vascular territories, such as the anterior and posterior cerebral arteries,
      might provide additional information on the onset of the brain sparing effect.
      The fractional moving blood volume estimation and three-dimensional power Doppler
      ultrasound indices are new techniques that seem to be promising in identifying
      cases at earlier stages of vascular deterioration; still, they are not available
      for clinical application and more information is needed on the reproducibility
      and advantages of three-dimensional power Doppler ultrasound blood flow indices.
      In the past, the brain sparing effect was considered as a protective mechanism;
      however, recent information challenges this concept. There is growing evidence of
      an association between brain sparing effect and increased risk of abnormal
      neurodevelopment after birth. Even in mild late-onset intrauterine growth
      restriction affected fetuses with normal umbilical artery blood flow, increased
      cerebral blood perfusion can be associated with a substantial risk of abnormal
      neuroadaptation and neurodevelopment during childhood.

PMID- 22418952
TI  - Cardiac biometry and function in euploid fetuses with intracardiac echogenic
      foci.
AB  - OBJECTIVE: To compare cardiac biometry and function between fetuses with and
      without intracardiac echogenic foci (ICEF). METHODS: One hundred and fifty-two
      fetuses with ICEF were compared with 104 controls. Diastolic ventricular
      transverse diameters, systolic aortic and pulmonary diameters and
      interventricular septum were measured. Doppler measurements included pulmonary
      artery and aortic maximum systolic velocities, time to peak, velocity time
      integral and atrioventricular E/A ratios. RESULTS: Only A wave in the mitral
      valve was slightly but significantly higher in the ICEF group (0.45 +/- 0.07 m/s
      vs 0.43 +/- 0.08 m/s, p = 0.03), but mitral E/A ratio was similar in both groups
      (0.61 +/- 0.06 vs 0.60 +/- 0.07, p = 0.22). There were no statistically
      significant differences in the rest of the studied variables between the two
      groups. CONCLUSION: Fetuses with ICEF do not have relevant abnormalities in
      either cardiac biometry or function. We suggest the presence of an isolated ICEF
      should not be an indication for fetal echocardiography as long as fetal
      morphology scan had been performed and revealed no other findings.

PMID- 22418953
TI  - Maternal serum placental growth factor in second trimester trisomy 21
      pregnancies.
AB  - OBJECTIVE: To investigate the levels of placental growth factor (PlGF) in second
      trimester maternal serum in trisomy 21 cases and euploid controls - an unclear
      subject in the published literature. METHODS: Second trimester maternal serum
      samples from 17 recent (since 2005) and 74 older trisomy 21 cases and 542 euploid
      controls were extracted from frozen storage and retrospectively analysed for PlGF
      using a DELFIA Xpress immunoassay platform. Results were converted to multiples
      of median (MoM) for comparison. RESULTS: The control group had a PlGF MoM of
      0.99, the recent trisomy 21 cases had a PlGF MoM of 1.13 and the older cases a
      PlGF MoM of 1.11; however, the differences between trisomy 21 cases and controls
      were not significant. CONCLUSION: Although we have found no significant change in
      the second trimester levels of PlGF in trisomy 21 pregnancies, there remains wide
      disagreement within the literature on the behaviour of this marker during
      pregnancies of this syndrome.

PMID- 22418954
TI  - Fetal reduction of triplet pregnancy: one or two?
AB  - OBJECTIVE: To review outcomes following reductions in trichorionic triplet
      pregnancies at our institution. METHOD: Retrospective analysis of the outcome of
      trichorionic triamniotic triplets reduced to singletons (group I, n = 44) or
      twins (group II, n = 136) at 10 and 12 weeks of gestation. RESULTS: Reduction to
      one or two was based on parent's preference, hence unrelated to any specific
      obstetrical or maternal issue. Early fetal loss rate (e.g. <24 weeks) was 9.1% in
      group I versus 5.1% in group II (p = 0.83). In group I, the take-home baby rate
      was 86.4% versus 91.9% in group II (p = 0.8). In group I, 17.5% of the women gave
      birth between 33 and 36(+6) weeks of gestation versus 40.6% in group II (p =
      0.026). Delivery beyond 37 weeks was 72.5% in group I and 46.9% in group II (p =
      0.01). Intrauterine growth restriction rate was 27.0% in group I versus 45.0% in
      group II (p = 0.049). CONCLUSION: Reduction to one rather than two fetuses led to
      significantly higher term delivery rate without significant differences in fetal
      loss rate or take-home baby rate.

PMID- 22418955
TI  - Evaluation of the measurement of the middle cerebral artery peak systolic
      velocity before and after placental laser coagulation in twin-to-twin transfusion
      syndrome.
AB  - OBJECTIVE: The aim of this study is to evaluate the incidence of elevated middle
      cerebral artery peak systolic velocity (MCA-PSV) in twin-to-twin transfusion
      syndrome (TTTS) before and after laser and its predictive value for intrauterine
      fetal death (IUFD) occurring within 2 to 7 days following laser. METHOD: This is
      a 5-year retrospective single-center study on 86 consecutive laser procedures for
      TTTS. MCA-PSV was measured prior to and 48 h following laser. We correlated
      perioperative MCA-PSV and fetal survival within 7 days following laser. RESULTS:
      The incidence of elevated MCA-PSV prior to and following laser (NS) was 8.2% to
      9.7% (non significant (NS)). There was no correlation between the incidence of an
      elevated MCA-PSV prior to laser and fetal survival up to 7 days after laser (NS,
      chi(2) :3.49). In contrast, the presence of an MCA-PSV above 1.5 MoM 48 h
      following laser in the former donor puts the former donor at a higher risk for
      IUFD within a week after surgery [odds ratio (OR):3.42 (interval of confidence
      (IC) 95%:1.9-30.6), chi(2) :8.68, p < 0.003]. CONCLUSION: The occurrence of an
      elevated MCA-PSV following laser is related to postoperative donor death within 2
      to 7 days after laser.

PMID- 22418956
TI  - Evaluation of placental syndecan-1 expression in early pregnancy as a predictive
      fetal factor for pregnancy outcome.
AB  - OBJECTIVE: Early expression of syndecan-1, a regulator of growth factor and
      chemokine function, in animal and human abortuses or placenta at delivery
      suggests a potential role during embryonic development. The aim of this study was
      to examine the correlation between early placental syndecan expression and fetal
      outcome in ongoing pregnancies. METHODS: Prospective immunohistochemical analysis
      of 203 chorionic villus sampling specimens obtained during a 4-year period (2001
      2004). The chorionic villi were processed for paraffin-embedded
      immunohistochemistry. Scores of intensity of syndecan-1 expression in chorionic
      villi were correlated with maternal cofactors and pregnancy outcome. RESULTS:
      Syndecan-1 immunostaining was significantly related to villus size, maternal
      tobacco use, and fetal biometry at ultrasonography. After correcting the above
      confounders, scores of syndecan-1 expression correlated with preterm birth and
      low birth weight. CONCLUSIONS: Placental syndecan-1 expression is associated with
      premature birth and fetal growth.

PMID- 22418957
TI  - Sequential testing for Down syndrome: the impact on estimated risk.
AB  - OBJECTIVE: Our objective was to describe the utilization of sequential screening
      and evaluate the impact on estimated Down syndrome risk. METHODS: We reviewed
      records of all those undergoing first-trimester screening over a 3-year period.
      All patients received first-trimester Down syndrome risk, and had options of
      invasive testing and sequential testing. We compared adjusted first-trimester
      Down syndrome risk with adjusted risk following sequential testing. Fisher's
      exact test and chi-square for trend were used for statistical comparison.
      RESULTS: First-trimester screening was performed on 12,557 patients. The rate of
      sequential testing was 34.0%. In 13.1% of patients, sequential testing resulted
      in a higher risk compared with first-trimester risk, with a risk at least twice
      as high in 5.2%. The likelihood that sequential testing would increase risk
      progressively decreased as first-trimester risk declined, from 17.8% for those
      with first-trimester risk of >1 in 270 to 8.7% in those with first-trimester risk
      of <1 in 10,000 (p < .001). For those with first-trimester risk <1 in 2000, the
      likelihood that sequential testing would adjust risk to >1 in 270 was <1%.
      CONCLUSIONS: Sequential testing lowers the Down syndrome risk in most cases and
      is more likely to do so with decreasing first-trimester risk.

PMID- 22418958
TI  - Prenatal diagnosis of Down syndrome: a systematic review of termination rates
      (1995-2011).
AB  - OBJECTIVE: The objective of this study was to review the published literature on
      pregnancy termination following a prenatal diagnosis of Down syndrome in the
      United States. METHOD: A systematic search of US English-language articles (1995
      2011) was conducted to identify primary research studies that reported data for
      pregnancies with definitive prenatal diagnosis of Down syndrome with subsequent
      pregnancy termination. Studies that provided indirect estimates of pregnancy
      termination, such as mathematical models, were excluded. The weighted mean
      termination rate was calculated across studies. RESULTS: Twenty-four studies were
      accepted. The weighted mean termination rate was 67% (range: 61%-93%) among seven
      population-based studies, 85% (range: 60%-90%) among nine hospital-based studies,
      and 50% (range: 0%-100%) among eight anomaly-based studies. Evidence suggests
      that termination rates have decreased in recent years. Termination rates also
      varied with maternal age, gestational age, and maternal race/ethnicity.
      CONCLUSION: This systematic review presents the largest synthesis of United
      States data on termination rates following a prenatal diagnosis of Down syndrome.
      Evidence suggests that termination rates are lower than noted in a previous
      review that was based on less contemporary studies and had an international
      focus. Heterogeneity across studies suggests that a summary termination rate may
      not be applicable to the entire US population.

PMID- 22418959
TI  - Aneuploidy screening during pregnancy by a three-dimensional Advanced First
      Trimester Screening model: description of the AFS-3D algorithm.
AB  - BACKGROUND: A novel screening method for fetal aneuploidies was developed, in
      which nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A),
      and free-beta human chorionic gonadotropin (free-beta hCG) are placed into a
      three-dimensional scatter plot. Likelihood ratios are directly inferred from the
      ratio of already observed healthy and diseased fetuses. This method is called
      'Three-dimensional Advanced First trimester Screening' (AFS-3D). It was aimed to
      develop and test a new algorithm based on the results of previous studies.
      METHODS: A new static-sized sphere model was developed. Several scaling factors
      of the axes and the optional application of the modifications 'simulation' (SIM)
      and 'empty sphere positive' were tested on 15,227 data sets. An additional
      examination was performed on a second collective (n = 458). RESULTS: The
      application of the new AFS-3D model with static-sized spheres, a re-sampled ?NT
      axis by a scaling factor of 0.125, and the application of SIM and Empty Box
      Positive resulted in a marked improvement of the test performance (area under
      curve, AUC = 0.9668). Analogous results (AUC = 0.9807) were found for the second
      test collective. CONCLUSIONS: This novel approach is promising and should be
      tested on a larger, independent collective.

PMID- 22418960
TI  - Effect of parity and fetal sex on placental and luteal hormones during early
      first trimester.
AB  - OBJECTIVE: Earlier studies have shown that maternal hormone secretion during late
      first or second trimester may be affected by gravidity. We examined the
      luteoplacental hormone secretion during 5-11 weeks of gestation in relation to
      gravidity. METHOD: Forty-one naturally conceived pregnancies underwent weekly
      assessment of serum human chorionic gonadotrophin, progesterone and 17-OH
      progesterone, estradiol, testosterone, and pregnancy-associated plasma protein A
      levels. In addition, the volume and the vasculature of the dominant ovary with
      corpus luteum were assessed with the use of a 3-dimensional power Doppler
      ultrasonography. Areas under the curve for hormonal and ultrasonographic
      parameters were calculated. RESULTS: Twenty-two out of the 41 women were pregnant
      for the first time. All the pregnancies were uncomplicated and resulted in term
      deliveries of appropriately grown newborns. During pregnancy weeks 5-11, the
      secretion (area under the curve) of human chorionic gonadotrophin (6.54 +/- 0.03
      vs 6.39 +/- 0.05, p = 0.010), progesterone (3.49 +/- 0.02 vs 3.36 +/- 0.03, p =
      0.003), and 17-OH progesterone (2.73 +/- 0.03 vs 2.62 +/- 0.03, p = 0.013) were
      higher in primigravid than in multigravid women. No other differences were
      detected between primigravid and multigravid women. CONCLUSION: The placental
      function already differs between primigravid and multigravid women during the
      first weeks of pregnancy, which reflects the corpus luteal function.

PMID- 22418961
TI  - Fetal heart disease and interruption of pregnancy: factors influencing the
      parental decision-making process.
AB  - OBJECTIVE: To identify factors influencing parental decision when a fetal cardiac
      disease is diagnosed. METHOD: All pregnancies with fetal cardiac abnormalities
      diagnosed at three academic hospitals of Marseille, France, between 2004 and
      2008, were retrospectively studied. The association between maternal and fetal
      variables (maternal age, parity, ethnicity, gestational age at diagnosis, nuchal
      translucency, fetal gender, chromosomal and extra cardiac abnormalities, and
      severity of the cardiopathy) and parental decision was tested using univariate
      and multivariate statistical methods RESULTS: One hundred eighty-eight cases of
      fetal cardiac disease were analysed, of which 63 were interrupted pregnancies
      (IP) and 125 continued pregnancies (CP). Four factors were important in the
      parental decision-making process: the severity of cardiac malformation, the
      ethnic origin of the parents, the gestational age at diagnosis and the
      chromosomal abnormalities. CONCLUSION: Counselling of parents following the
      diagnosis of a congenital heart disease should take into account that, in
      addition of the severity of the congenital heart disease (CHD), ethnicity,
      gestational age at diagnosis and chromosomal abnormalities influence parental
      decision regarding pregnancy continuation or interruption.

PMID- 22418962
TI  - Klinefelter twins presenting with discordant aneuploidies, acardia, forked
      umbilical cord and with different gonadal sex despite monozygosity.
AB  - OBJECTIVE: A higher frequency of twin births in sibships of Klinefelter syndrome
      patients and also monozygotic or dizygotic twins, themselves being affected by
      Klinefelter syndrome have been noted repeatedly. To address this issue, we
      evaluated type and frequency of twinning among Klinefelter fetuses that we had
      received for autopsy within a 'Prenatal Diagnosis' program. METHOD: We performed
      fetal autopsies, and genetic analyses on DNA extracted from stained histological
      slides. RESULTS: Among 41 prenatal diagnoses of a 47, XXY karyotype we observed
      four twin pairs. One was dizygotic with discordant Klinefelter and Down syndrome.
      Three twin pairs were monozygotic as concluded from monochorial placentation. In
      two monozygotic pairs one twin partner was an acardiac monster and in one of
      these the acardiac twin showed a female gonadal sex and missing Y-chromosomal SRY
      sequences as confirmed by polymerase chain reaction. CONCLUSIONS: There is a high
      rate of twinning and twin reversed arterial perfusion sequence among our
      Klinefelter fetuses. Forked umbilical cords at the placental insertion site in
      one case allowed classification as conjoined twins in the sense of a
      'funiculopagus'. Anaphase lagging or semidizygosity by second polar body twinning
      are proposed as explanations for the gonadal sex discordance and the excessive
      developmental disadvantage in the one acardiac. Problems may arise with regard to
      non-invasive prenatal diagnosis of aneuploidies in twin pregnancies.

PMID- 22418963
TI  - Screening for pre-eclampsia by using changes in uterine artery Doppler indices
      with advancing gestation.
AB  - OBJECTIVE: The aim of the study was to assess the relationship of changes in
      uterine artery (UtA) Doppler pulsatility indices (PI) between first and second
      trimesters and the subsequent development of pre-eclampsia. METHODS: A
      retrospective study of singleton pregnancies undergoing both first and second
      trimesters UtA Doppler screening between 2002 and 2009 was conducted. Multiples
      of median of UtA Doppler PI were used for developing indices describing UtA
      changes between the two trimesters. Receiver-operating characteristics curves
      (ROC) were calculated for multiple comparisons. RESULTS: Three thousand five
      hundred sixty women had UtA Doppler screening in the first and second trimesters.
      Eleven women were excluded because of termination of pregnancy before 24 weeks.
      Out of the 3549 women recruited, 126 developed Pre-eclampsia (PE; 22 early PE
      delivered <34 weeks and 41 preterm PE delivered <37 weeks). The best index for
      predicting pre-eclampsia was the difference between the mean second trimester and
      mean first trimester UtA PI (areas under the ROC for early PE and preterm PE of
      0.851 and 0.786, respectively). CONCLUSION: Changes of UtA resistance between the
      first and second trimesters can be calculated as the difference between UtA PI at
      these gestations. The data of this study demonstrate that the difference in mean
      PI is the best index in predicting early PE and preterm PE.

PMID- 22418964
TI  - Prenatal diagnosis of 'isolated' Dandy-Walker malformation: imaging findings and
      prenatal counselling.
AB  - OBJECTIVE: The purpose of this article is to improve prenatal imaging diagnosis
      and counselling for cases of 'isolated' Dandy-Walker malformation (DWM) in the
      light of recent literature, which has demonstrated a potential good clinical and
      intellectual outcome of fetuses presenting with DWM characterised by partial
      vermian agenesis (identification of two fissures and three lobes) and absence of
      associated anatomical anomalies. METHODS: This is a retrospective observational
      study of six consecutive prenatal cystic posterior fossa malformations, diagnosed
      as DWM, encountered in a national reference centre for posterior fossa
      malformations over a 2-year period. RESULTS: In all cases, DWM was diagnosed as
      isolated (without any associated central nervous system or extra-central nervous
      system malformations and normal standard karyotype). Despite good-quality
      imaging, including fetal magnetic resonance imaging (MRI), prenatal analysis of
      the vermis was impossible because of limited identification of fissuration and
      lobulation. In three cases, a cytogenetic anomaly was found, including 6p
      subtelomeric deletion (n = 2) and partial 4 qter deletion associated with partial
      7p trisomy (n = 1). One fetus with 6p deletion was terminated. In four of the
      five postnatal cases, MRI confirmed the diagnosis of DWM but provided only
      limited information for vermian analysis. In one case, postnatal MRI showed a
      large Blake's pouch cyst with rotated but complete vermis associated with a
      marked mass effect on the distal part of the tentorium. Of the four babies born
      with postnatal diagnosis of DWM, all required ventriculoperitoneal shunting
      because of early postnatal hydrocephalus. CONCLUSION: When fetal MRI is necessary
      to exclude additional cerebral lesions in the diagnosis of DWM, we highlight the
      inaccuracy of magnetic resonance for anatomical analysis of the vermis. We also
      emphasise the potential high incidence of subtelomeric anomalies in isolated DWM,
      especially 6p deletion. In the postnatal period, paediatricians should look for
      postnatal hydrocephalus even if the ventricular size is normal or slightly
      dilated on prenatal imaging.

PMID- 22418965
TI  - Prenatal diagnosis of a left coronary artery to left atrial fistula.

PMID- 22418966
TI  - Comments on Arigita et al. Spina bifida in a 13-week fetus with a normal
      intracranial translucency, Prenat Diagn 2011.

PMID- 22418967
TI  - Comment on the paper 'Spina bifida in a 13-week fetus with a normal intracranial
      translucency' published in Prenatal Diagnosis by Arigita et al. 2011.

PMID- 22418968
TI  - Re: Spina bifida in a 13-week fetus with a normal intracranial translucency.

PMID- 22418969
TI  - Correspondence regarding research letter published by Arigita et al.

PMID- 22418971
TI  - [Ultrasound in the diagnostic management of malignant lymphomas].
AB  - Ultrasound is most useful in detecting and characterizing peripheral and
      abdominal lymph nodes and infiltration of solid organs. B-mode criteria, such as
      size, shape, number, distribution architecture, echogenicity and delineation of
      margins are the basis for characterizing lymph nodes. Additionally color coding
      techniques such as color Doppler, B-flow and contrast-enhanced ultrasound (CEUS)
      contribute to the evaluation of the nodal vasculature and vessel architecture.
      Whenever possible high frequency probes should not only be used for evaluating
      peripheral lymph nodes but also for lymphatic infiltration of solid organs,
      especially the spleen. The CEUS technique will be of additional benefit in
      detecting characterizing potential lymphatic organ infiltration. Ultrasound is an
      ideal tool for guided punctures, for which core biopsies should be preferred over
      fine needle aspiration biopsy and CEUS can also be used for proving residual
      viable tissue after chemotherapy or radiation therapy.

PMID- 22418972
TI  - [Response criteria for malignant lymphoma].
AB  - CLINICAL/METHODICAL ISSUE: A proven criterion for assessing tumor response is the
      increase in tumor size. Unlike most tumors, lymph nodes are normal anatomical
      structures and can be measured even when benign. The International Working Group
      (IWG) criteria for lymphomas therefore combine morphological with functional
      (positron emission tomography PET) and biopsy (bone marrow biopsy) parameters.
      The IWG criteria have been established as the standard in clinical trials and
      take nodal involvement, spleen, liver involvement as well as bone marrow
      involvement into account, which makes the response evaluation complex. STANDARD
      RADIOLOGICAL METHODS: This involves an investigator-dependent, non-standardized
      and poorly reproducible estimation of tumor response to therapy. METHODICAL
      INNOVATIONS: The formulation of standardized response categories for malignant
      lymphomas. PERFORMANCE: The aim was to produce uniform and standardized criteria
      for application in medication studies. ACHIEVEMENTS: Established as the standard
      for medication studies but too time-consuming for practical application.
      PRACTICAL RECOMMENDATIONS: An improved practicability can be achieved by
      incorporating a computer-assisted evaluation program.

PMID- 22418973
TI  - [Malignant lymphomas: clinical appearance, classification, therapy and
      prognosis].
AB  - CLINICAL ISSUE: Malignant lymphomas are the most common cancers of the
      hematopoietic system. STANDARD TREATMENT: The treatment is usually cytotoxic
      chemotherapy after the appearance of symptoms in indolent lymphoma and
      immediately in aggressive lymphoma. Local therapy, such as radiotherapy is
      sometimes required in addition to systemic treatment. TREATMENT INNOVATIONS: By
      the introduction of targeted therapies the prognosis has improved. The monoclonal
      antilymphoma antibody rituximab is a prototype for many other cancers. DIAGNOSTIC
      WORK-UP: A biopsy is mandatory for diagnosis. Additional immunohistological and
      molecular genetic analyses may provide prognostic information. Imaging
      techniques, such as computed tomography (CT), ultrasound or positron emission
      tomography (PET) are used for staging, restaging and follow-up. Following
      chemotherapy for Hodgkin's disease PET can be considered to identify patients who
      do not require additional radiotherapy. PERFORMANCE: Aggressive lymphomas are
      often curable. In Hodgkin's disease the long-term survival rate is over 90% and
      in diffuse large cell lymphoma between 60-90%. Indolent lymphomas are not curable
      by standard therapy, however, the survival rate is also high. ACHIEVEMENTS: After
      introduction of rituximab, the survival chance has improved by at least 10% in
      both indolent and aggressive lymphomas. Other targeted therapies and autologous
      or allogeneic transplantation have made additional contributions. PRACTICAL
      RECOMMENDATIONS: Due to the rapid increase of knowledge patients should be
      treated in experienced centers and whenever possible, in clinical trials. Using
      molecular genetic analyses and functional imaging, the treatment can be
      individualized even more.

PMID- 22418974
TI  - Squeeze-chip: a finger-controlled microfluidic flow network device and its
      application to biochemical assays.
AB  - We designed and fabricated a novel microfluidic device that can be operated
      through simple finger squeezing. On-chip microfluidic flow control is enabled
      through an optimized network of check-valves and squeeze-pumps. The sophisticated
      flow system can be easily constructed by combining a few key elements. We
      implemented this device to perform quantitative biochemical assays with no
      requirement for precision instruments.

PMID- 22418976
TI  - Retracted article: Donor site morbidity of the vascularized fibula: the Hamburg
      experience.

PMID- 22418977
TI  - Thrombospondin-1 plays a profibrotic and pro-inflammatory role during ureteric
      obstruction.
AB  - Thrombospondin-1 (TSP-1) is an endogenous activator of transforming growth factor
      beta (TGF-beta), and an anti-angiogenic factor, which may prevent kidney repair.
      Here we investigated whether TSP-1 is involved in the development of chronic
      kidney disease using rats with unilateral ureteral obstruction, a well-known
      model to study renal fibrosis. Obstruction of 10 days duration induced
      inflammation, tubular cell atrophy, dilation, apoptosis, and proliferation,
      leading to interstitial fibrosis. TSP-1 expression was increased in parallel to
      that of collagen III and TGF-beta. Relief of the obstruction at day 10 produced a
      gradual improvement in renal structure and function, the reappearance of
      peritubular capillaries, and restoration of renal VEGF content over a 7- to 15
      day post-relief period. TSP-1 expression decreased in parallel with that of TGF
      beta1 and collagen III. Mice in which the TSP-1 gene was knocked out displayed
      less inflammation and had better preservation of renal tissue and the peritubular
      capillary network compared to wild-type mice. Additional studies showed that the
      inflammatory effect of TSP-1 was mediated, at least in part, by monocyte
      chemoattractant protein-1 and activation of the Th17 pathway. Thus, TSP-1 is an
      important profibrotic and inflammatory mediator of renal disease. Blockade of its
      action may be a treatment against the development of chronic kidney disease.

PMID- 22418978
TI  - Impaired sodium excretion and salt-sensitive hypertension in corin-deficient
      mice.
AB  - Corin is a protease that activates atrial natriuretic peptide, a cardiac hormone
      important in the control of blood pressure and salt-water balance. Here we
      examined the role of corin in regulating blood pressure and sodium homeostasis
      upon dietary salt challenge. Radiotelemetry-tracked blood pressure in corin
      knockout mice on a high-salt diet (4% sodium chloride) was significantly
      increased; however, there was no such change in similarly treated wild-type mice.
      In the knockout mice on the high-salt diet there was an impairment of urinary
      sodium excretion and an increase in body weight, but no elevation of plasma renin
      or serum aldosterone levels. When the knockout mice on the high-salt diet were
      treated with amiloride, an epithelial sodium channel blocker that inhibits renal
      sodium reabsorption, the impaired urinary sodium excretion and increased body
      weight were normalized. Amiloride treatment also reduced high blood pressure
      caused by the high-salt diet in these mice. Thus, the lack of corin in mice
      impairs their adaptive renal response to high dietary salt, suggesting that corin
      deficiency may represent an important mechanism underlying salt-sensitive
      hypertension.

PMID- 22418979
TI  - Some biomarkers of acute kidney injury are increased in pre-renal acute injury.
AB  - Pre-renal acute kidney injury (AKI) is assumed to represent a physiological
      response to underperfusion. Its diagnosis is retrospective after a transient rise
      in plasma creatinine, usually associated with evidence of altered tubular
      transport, particularly that of sodium. In order to test whether pre-renal AKI is
      reversible because injury is less severe than that of sustained AKI, we measured
      urinary biomarkers of injury (cystatin C, neutrophil gelatinase-associated
      lipocalin (NGAL), gamma-glutamyl transpeptidase, IL-18, and kidney injury
      molecule-1 (KIM-1)) at 0, 12, and 24 h following ICU admission. A total of 529
      patients were stratified into groups having no AKI, AKI with recovery by 24 h,
      recovery by 48 h, or the composite of AKI greater than 48 h or dialysis. Pre
      renal AKI was identified in 61 patients as acute injury with recovery within 48 h
      and a fractional sodium excretion <1%. Biomarker concentrations significantly and
      progressively increased with the duration of AKI. After restricting the AKI
      recovery within the 48 h cohort to pre-renal AKI, this increase remained
      significant. The median concentration of KIM-1, cystatin C, and IL-18 were
      significantly greater in pre-renal AKI compared with no-AKI, while NGAL and gamma
      glutamyl transpeptidase concentrations were not significant. The median
      concentration of at least one biomarker was increased in all but three patients
      with pre-renal AKI. Thus, the reason why some but not all biomarkers were
      increased requires further study. The results suggest that pre-renal AKI
      represents a milder form of injury.

PMID- 22418980
TI  - A multiplex quantitative proteomics strategy for protein biomarker studies in
      urinary exosomes.
AB  - Urinary exosomes have received considerable attention as a potential biomarker
      source for the diagnosis of renal diseases. Notwithstanding, their use in protein
      biomarker research is hampered by the lack of efficient methods for vesicle
      isolation, lysis, and protein quantification. Here we report an improved
      ultracentrifugation-based method that facilitates the solubilization and removal
      of major impurities associated with urinary exosomes. A double-cushion
      sucrose/D(2)O centrifugation step was used after a two-step differential
      centrifugation to separate exosomes from the heavier vesicles. After the removal
      of uromodulin, 378 and 79 unique proteins were identified, respectively, in low-
      and high-density fractions. Comparison of our data with two previously published
      data sets helped to define proteins commonly found in urinary exosomes. Lysis,
      protein extraction, and in-solution digestion of exosomes were then optimized for
      MudPIT application. More than a hundred exosomal proteins were quantified by four
      plex iTRAQ analysis of single and pooled samples from two different age groups.
      For healthy men, six proteins (TSN1, PODXL, IDHC, PPAP, ACBP, and ANXA5) showed
      significant expression differences between exosome pools of those aged 25-50 and
      50-70 years old. Thus, exosomes isolated by our method provide the basis for the
      development of robust quantitative methods for protein biomarker research.

PMID- 22418981
TI  - Increased dietary sodium is independently associated with greater mortality among
      prevalent hemodialysis patients.
AB  - Dietary sodium is thought to play a major role in the pathogenesis of
      hypertension, hypervolemia, and mortality in hemodialysis patients; hence, sodium
      restriction is almost universally recommended. Since the evidence upon which to
      base these assumptions is limited, we undertook a post-hoc analysis of 1770
      patients in the Hemodialysis Study with available dietary, clinical, and
      laboratory information. Within this cohort, 772 were men, 1113 black, and 786
      diabetic, with a mean age of 58 years and a median dietary sodium intake of 2080
      mg/day. After case-mix adjustment, linear regression modeling found that higher
      dietary sodium was associated with a greater ultrafiltration requirement, caloric
      and protein intake; sodium to calorie intake ratio was associated with a greater
      ultrafiltration requirement; and sodium to potassium ratio was associated with
      higher serum sodium. No indices were associated with the pre-dialysis systolic
      blood pressure. Cox regression modeling found that higher baseline dietary sodium
      and the ratio of sodium to calorie or potassium were each independently
      associated with greater all-cause mortality. No association between a prescribed
      dietary sodium restriction and mortality were found. Thus, higher reported
      dietary sodium intake is independently associated with greater mortality among
      prevalent hemodialysis patients. Randomized trials will be necessary to determine
      whether dietary sodium restriction improves survival.

PMID- 22418982
TI  - Deletion of the epidermal growth factor receptor in renal proximal tubule
      epithelial cells delays recovery from acute kidney injury.
AB  - To determine the role of epidermal growth factor receptor (EGFR) activation in
      renal functional and structural recovery from acute kidney injury (AKI), we
      generated mice with a specific EGFR deletion in the renal proximal tubule
      (EGFR(ptKO)). Ischemia-reperfusion injury markedly activated EGFR in control
      littermate mice; however, this was inhibited in either the knockout or wild-type
      mice given erlotinib, a specific EGFR tyrosine kinase inhibitor. Blood urea
      nitrogen and serum creatinine increased to a comparable level in EGFR(ptKO) and
      control mice 24 h after reperfusion, but the subsequent rate of renal function
      recovery was markedly slowed in the knockout mice. Twenty-four hours after
      reperfusion, both the knockout and the inhibitor-treated mice had a similar
      degree of histologic renal injury as control mice, but at day 6 there was minimal
      evidence of injury in the control mice while both EGFR(ptKO) and erlotinib
      treated mice still had persistent proximal tubule dilation, epithelial
      simplification, and cast formation. Additionally, renal cell proliferation was
      delayed due to decreased ERK and Akt signaling. Thus, our studies provide both
      genetic and pharmacologic evidence that proximal tubule EGFR activation plays an
      important role in the recovery phase after acute kidney injury.

PMID- 22418983
TI  - Evaluation of the possible antioxidative role of bilirubin protecting from free
      radical related illnesses in neonates.
AB  - There are disparate data regarding whether bilirubin is protective or toxic
      during free radical related illness among neonates. Seventy one infants with
      gestational age (GA) of <32 weeks and/or birth weight (BW) of <1500 g, who
      survived beyond 4 weeks and completed physical examinations were enrolled in this
      study. The infants were divided into two groups based on the presence or absence
      of advanced retinopathy of prematurity (ROP), grade III intraventricular
      hemorrhage (IVH), grade III necrotizing enterocolitis (NEC), respiratory distress
      syndrome (RDS), bronchopulmonary dysplasia (BPD), sepsis or severe fungal
      infection (SFI). The mean of total serum bilirubin (TSB) of the first 14 days of
      life were measured and compared between these two groups. A significant lower TSB
      were found in severe form of ROP (P<0.001), grade III NEC (P=0.008), grade III
      IVH (P=0.021), SFI (P=0.003) and sepsis (P=0.007) in comparison to mild or
      disease free status. Moreover, the cut-off point of 5.1 mg/dl for the mean of TSB
      had the sensitivity of 88.1% and specificity of 84.6% to detect severe grades of
      ROP. Also the cut-off point of 3.25 mg/dl had 97.2% sensitivity and 100%
      specificity in order to distinguish SFI. It is concluded that bilirubin may play
      an antioxidant role in vivo as in vitro; and protect preterm infant against these
      free radical related disorders. Our findings suggest that not only the upper
      limits of serum bilirubin, but also the lower limits must be taking into account
      in order to both preventing from neurotoxic effects and free radical based
      illnesses, respectively.

PMID- 22418984
TI  - In vitro effects of triclabendazole (TCBZ) on the excretory-secretory products
      (ESP) of Fasciola spp parasites.
AB  - Fascioliasis is an endemic disease in Iran and triclabendazole (TCBZ) is using
      for treatment of domestic animals and infected people. Excretory-secretory
      products (ESP) play an important role in the host biochemical defense by means of
      activities of detoxifying and antioxidant glutathione S-transferase (GST) and
      superoxide dismutase (SOD) enzymes respectively. Therefore, the aim of this
      comparative study was to evaluate fasciola protection against TCBZ drug by
      detection of enzymatic activities, GST and SOD, in TCBZ treated Fasciola hepatica
      / Fasciola gigantica and control ESP samples. F. gigantic and F. hepatica
      helminthes were collected and cultured within buffer media (TCBZ treated and
      untreated or control) for 4 h at 37  degrees C. Three TCBZ treated and 1 control
      ESP samples for each species were collected, centrifuged and supernatants were
      stored at -20 degrees C. ESP samples protein concentrations were measured by
      Bradford method. SOD and GST enzymes activities of ESP samples were estimated
      photometrically. To determine the statistically significant difference between
      ESP of treated and control samples, t-test was conducted. ESP protein bands were
      detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).
      Protein concentrations in treated F. hepatica and F. gigantica ESP samples were
      estimated 204.88, 428, 130.4 and 288.2, 488.2, 308.2 ug/ml respectively. Protein
      concentrations in control samples were estimated 488.18 and 124.8 ug/ml
      respectively. SOD enzyme specific activities level in treated F.hepatica and F.
      gigantica ESP samples were determined 0.14, 0.31, 3.96 and 11.11, 13.54, 19.95
      U/mg/protein respectively. SOD activities level in control samples were detected
      70.69 and 10.92 U/mg/protein. GST specific activities level in treated F.hepatica
      and F. gigantica ESP samples were calculated 25.3, 85.5, 37.3 and 1823, 1314.3,
      1320.8 U/mg respectively. GST activities levels in control samples were detected
      98.6 and 1083.9 U/mg/protein respectively. Statistical analysis reveal the
      significant different between proteins concentrations, GST and SOD enzyme
      specific activities of TCBZ treated ESP samples of F. gigantic in comparison to
      the control samples (P<0.05), however, is not significant for treated F. hepatica
      and control ESP samples (P>0.05). There is no difference between SDS-PAGE results
      of treated and control samples. Based on the results of the present work,
      significant increase of enzymatic activities of GST and SOD in TCBZ treated F.
      gigantica ESP, it seems, the protection of this species against drug is higher
      than F. hepatica.

PMID- 22418985
TI  - Mental health problems of Iranian female adolescents and its association with
      pubertal development: a nationwide study.
AB  - Mental health problems including emotional and behavioral problems during puberty
      may be under influence of different risk factors including cultures, living in
      urban or rural areas and ethnic factors which may vary between different
      countries. The main aim of this study is to investigate the profile of emotional
      and behavioral problems and the role of factors such as age, stage of puberty,
      ethnicity, rurality and living in urban area, as risk factors in Iranian girls.
      As a part of a large national study we evaluated the emotional and behavioral
      problems in different stages of puberty in a community sample of Iranian
      adolescent girls from public schools that were selected by clustered random
      sampling method. In all subjects, demographic characteristics, and pubertal
      stages were measured. Emotional and behavioral problems were evaluated using
      Strength and Difficulties Questionnaire (SDQ). The associations of age, pubertal
      development indices, socioeconomic and demographic factors with the behavioral
      problems were assessed. A total number of 4576 students enrolled the study and
      responded to the questions. The mean age of participants was 13.83 +/- 2.19
      years. The mean total score of difficulties in participants was 14.34 +/- 5.81.
      According to these results 813 (17.8%) adolescents had total problem scores
      higher than Goodman's cutoff points and the most frequent problem domain was
      conduct problems (20.5%). According to the results the most related variable with
      the total difficulty score of SDQ were ethnicity, residency in urban areas and
      development of menstrual cycle respectively. The results of this study showed
      that the most correlated factors with mental health problems in Iranian girls
      during puberty are ethnicity, urbanity and development of menstrual cycle.

PMID- 22418986
TI  - BMI correlation with psychiatric problems among 10-18 years Iranian students.
AB  - Obesity and its related emotional and physical consequences are a worldwide
      problem. Obese individuals are usually stigmatized. This study is proposed to
      assess the correlation between body mass index, gender and age with psychiatric
      symptoms among Iranian students. A number of 9172 students aged 10-18 years
      (53.5% girls and 46.5% boys) from all provinces of Iran participated in this
      study. Data was collected using the global school based health survey
      questionnaire of the World Health Organization (GSHS-WHO). Overall, prevalence of
      predictors of having emotional problems, depression and anxiety were 27.8%, 29.7%
      and 11.5% respectively. Girls had significantly higher prevalence of predictors
      of psychiatric symptoms. Overall obesity was a protective factor against
      emotional problems OR (CI95%):0.79(0.65-0.98), but it was attributable to obese
      boys OR (CI95%):0.72(0.55-0.95). Depression and anxiety symptoms were higher in
      intermediate school girls and high school girls and boys. More attention should
      be paid to girls' psychological problems. Besides, obesity had an indirect
      relation with predictors of having psychiatric problems in Iranian boys and it
      might be due to: (1) parents' beliefs about heaviness as a predictor of
      healthiness, (2) boys' lower vulnerability to psychological consequences of
      obesity and (3) lower pressure from parents on their obese sons to lose weight.

PMID- 22418987
TI  - Electrocardiographic findings and serum troponin I in carbon monoxide poisoned
      patients.
AB  - Carbon monoxide (CO) poisoning, though with different sources, is one of the most
      deadly emergencies in all countries. CO can threaten men's life by several paths
      especially cardiac complications, which can mimic other cardiac problems such as
      myocardial infarction. The objective of this study was to determine ECG findings
      and serum troponin I levels in CO poisoned patients. In this analytical cross
      sectional study, 63 CO poisoning patients were consecutively included from
      hospital's emergency departments. CO content was measured by a CO-oximeter and an
      electrocardiography was taken first thing on admission. Arterial blood gas (ABG),
      troponin I and other data was collected afterwards. Data were divided by age
      groups (adults and children) and gender. CO content was significantly higher only
      in subjects with normal T wave compared to patients with inverted T wave in their
      initial ECG (P=0.016). No other significant difference was noticed. None of the
      ABG findings correlated significantly with CO content. Also no significant
      correlation was found with CO content after stratification by gender and age
      groups, but pH in children (r=-0.484, P=0.026). CO content was significantly
      higher in adults (P=0.023), but other ABG data were not significantly different.
      Only 3 patients had elevated troponin I. Receiver operating characteristic (ROC)
      analysis showed no significant cutoff points in CO content for ECG changes. No
      significant specific change in electrocardiograms (ECG) could contribute
      carboxyhemoglobin content in carbon monoxide poisoned patients. In addition, no
      specific difference was found between adults and pediatric subjects' ECGs. All
      other findings seemed to be accidental.

PMID- 22418988
TI  - Detection of acute childhood meningitis by PCR, culture and agglutination tests
      in Tabriz, Iran.
AB  - Meningitis is one of the hazardous and life threatening infections and is
      associated with mortality and morbidity. The aim of this study was to determine
      etiological agents of childhood bacterial meningitis. The culture, Gram staining,
      agglutination and PCR assays were used to examine CSF specimens from 277 patients
      with presumed bacterial meningitis for the occurrence of 4 most common infectious
      agents consist of N. meningitis, H. influnsae, S. pneumoniae and S. agalactiae
      between 2008 and 2009 at different wards of the Children Hospital of Tabriz. The
      mean age of patients was 35 +/- 2 (Mean +/- SEM) month, (minimum 11 days maximum
      14 years), of all cases 59.6% male and 40.4% female. Overall the diagnosis was
      confirmed with a CSF culture in 11/277 (3.97%), by agglutination test in 14/277
      (5.05%). The isolated bacteria included S. pneumoniae 5 cases, H. influnsae 2
      cases, N. meningitis 3 cases and P. aeroginusae 1 case. A positive PCR assay
      allowed us to diagnose bacterial meningitis in 19 patients (6.8%). In the present
      study, we found PCR to be a useful and sensitive method for the detection of
      bacterial DNA in the CSF samples from suspected meningitis patients. Furthermore,
      to maximize management of meningitis cases, a combination of culture and PCR is
      necessary.

PMID- 22418989
TI  - Significance of albumin and C-reactive protein variations in 300 end stage renal
      disease patients in Tehran University of Medical Sciences Hospitals during year
      2010.
AB  - Protein- energy malnutrition, wasting and inflammation are frequent complication
      among patients with end-stage renal disease (ESRD). Malnutrition is associated
      with cardiac co-morbidity, inflammation and poor survival in ESRD patients. Serum
      albumin is a well-known marker of nutrition in ESRD patients. Serum albumin is
      still the most commonly used nutritional marker in ESRD patients. C-reactive
      protein (CRP), the major acute phase response (APR) protein is elevated in these
      patients. High CRP levels are linked to the degree of atherosclerosis in
      coronary, peripheral, and extracranial brain arteries. The aim of the present
      study was to investigate nutritional factor (albumin) and CRP levels in ESRD
      patients. In this cross- sectional study a total of 300 patients who had ESRD and
      had been on hemodialysis treatment for at least 6 months were selected. The
      laboratory tests consisted of measurement of CRP and albumin using high sensitive
      ELISA kits. The study patients included 157 males (52.3%) and 143 females (47.7%)
      with average age of 41.5 +/- 14.3 years. Mean CRP level was 7.96 mg/ dl (+/
      1.52), mean serum albumin was 4.07 g/dl (+/-0.19).Of 300 patients, 21 died (7%).
      These were patients with serum albumin <4 g/dl and CRP>9.5 mg/dl. This study
      showed that low albumin and high CRP levels are the main predictors for death.
      There was a significant difference between CRP and albumin levels in ESRD
      patients (P<0.0001). Measuring CRP as a marker of inflammation can be helpful in
      managing these patients.

PMID- 22418990
TI  - Management of thoracic empyema: review of 112 cases.
AB  - To review our experience in treatment of patients with thoracic empyema at a
      teaching hospital chart of patients were retrospectively reviewed over a 72-month
      period. A total of 112 patients (94 men, 18 women, mean age: 39, range: 6-89
      years) underwent therapeutic procedures for thoracic empyema between 2001-2006.
      The causes of empyema included parapneumonic empyema (60.7%), thoracic trauma
      (20.5%), surgical procedures (7.1%) and seeding from an extra-pulmonary source
      (11.7%). Multiloculated empyemas were documented in 45 patients (40%). Insertion
      of chest tube was the first procedure in 103 patients (92%). Nineteen patients
      (17%) were treated by thoracotomy, ten patients (8.9%) had fibrinolytic therapy,
      eight patients (7.2%) underwent video assisted thoracic surgery (VATS) and
      sixteen patients (14.3%) had subsequent radiologic-guided drainage. Thoracotomy
      Decortication was successful in 90% of patients undergoing surgery and the least
      successful intervention was tube thoracostomy alone. Twelve of 112 patients
      (10.7%) died in the hospital including one patient in the thoracotomy group. Long
      term follow-up was available in 67 patients including all of patients requiring
      surgery and fibrinolytic therapy. Thirty four patients (50%) obtained complete
      functional recovery. Simple drainage as the first procedure for the treatment of
      thoracic empyema has a high failure rate. Selection of a therapeutic option
      should be based on age, underlying disease, stage of the empyema, state of the
      loculation, local expertise and availability. Surgical procedures such as VATS or
      thoracotomy are recommended as the first procedure in elderly patients and
      advanced empyema.

PMID- 22418991
TI  - Lack of association between the C677T single nucleotide polymorphism of the MTHFR
      gene and glaucoma in Iranian patients.
AB  - Glaucoma is a major cause of blindness worldwide. A single nucleotide
      polymorphism of the MTHFR gene (C677T) has been associated with susceptibility to
      this disease, although this is controversial in the last decade. In this study,
      the possible association between the MTHFR C677T polymorphism and the risk of
      developing primary open angle (POAG) and pseudoexfoliation glaucoma (PEXG) was
      investigated. For this, a prospective study consisting of 73 POAG, 85 PEXG and 90
      matched controls was undertaken in an Iranian population. Genomic DNA was
      extracted from whole blood. Genotyping of all individuals for the MTHFR C677T
      polymorphism was conducted using the PCR-RFLP technique. Our findings revealed no
      significant association between the MTHFR C677T polymorphism in POAG and PEXG
      compared with controls. Consistent with several other studies, our analysis
      suggests that the MTHFR C677T polymorphism is unlikely to be a factor
      contributing to the risk of developing specific forms of glaucoma.

PMID- 22418992
TI  - Bilateral dislocation of temporomandibular joint induced by haloperidol following
      suicide attempt: a case report.
AB  - Drug induced dystonic reactions are among common presentations of patients in
      emergency departments, and typically occur with antidopaminergic agents as their
      extra-pyramidal side effects. Dystonic reactions usually occur within the first
      few hours or days after commencing a drug or dose increase. Unlike other extra
      pyramidal side effects, a patient may experience acute dystonic reactions (ADRs)
      with the administration of just a single dose. Oromandibular dystonia is a
      subtype of dystonia which can present with perioral manifestations. In extreme
      cases, it can lead to temporomandibular dislocation. Haloperidol, as a high
      potent typical antipsychotic drug, can induce dystonia with blocking D2 dopamine
      receptors. The present paper reports a case of bilateral dislocation of
      temporomandibular joint following ingestion of haloperidol in a suicidal attempt
      in a 17 years old girl.

PMID- 22418993
TI  - Primary angiitis of the central nervous system.
AB  - Primary angiitis of the central nervous system (PACNS) is an idiopathic disorder
      (vasculitis) restricted to the central nervous system (CNS). It often presents
      with focal neurological deficits suggesting stroke or a combination of confusion
      and headache. We herein report three cases with various combinations of fever,
      partial seizure, encephalopathy, paresis, headache and ataxia. One of them was
      initially treated as herpes simplex meningoencephalitis, but further
      investigations revealed primary angiitis. Primary angiitis of the CNS has protean
      manifestations and should always be considered in patients suspicious to have CNS
      infection or stroke, particularly who does not respond to the routine treatments.
      Clinical data, exclusion of differential diagnoses and typical angiography seem
      to be enough to justify the diagnosis in the majority of cases.

PMID- 22418994
TI  - Chondroma of falx: case report of a rare condition.
AB  - Chondroma is a benign tumor which mostly occurs in extremities but also sometimes
      in brain. Most intracranial chondromas arise from skull base, but chondroma of
      falx origin is a rare circumstance. Indeed, the intracranial chondromas rise from
      falx is mostly in relation with syndromic disorders such as Mafucci's syndrome or
      Ollier's syndrome. Here, we reported a rare case of falxian intracranial
      chondroma in a young man who has normal physical examination and no signs of any
      syndromic disorder. The goal of this paper was to raise awareness about
      chondromas and suggest that chondroma be ruled out in any patient with masses
      arising from falx.

PMID- 22418995
TI  - In vivo assessment of retinal neuronal layers in multiple sclerosis with manual
      and automated optical coherence tomography segmentation techniques.
AB  - Macular optical coherence tomography (OCT) segmentation, enabling quantification
      of retinal axonal and neuronal subpopulations, may help elucidate the
      neuroretinal pathobiology of multiple sclerosis (MS). This study aimed to
      determine the agreement, reproducibility, and visual correlations of retinal
      layer thicknesses measured by different OCT segmentation techniques, on two
      spectral-domain OCT devices. Macular scans of 52 MS patients and 30 healthy
      controls from Spectralis OCT and Cirrus HD-OCT were segmented using fully manual
      (Spectralis), computer-aided manual (Spectralis and Cirrus), and fully automated
      (Cirrus) segmentation techniques. Letter acuity was recorded. Bland-Altman
      analyses revealed low mean differences across OCT segmentation techniques on both
      devices for ganglion cell + inner plexiform layers (GCIP; 0.76-2.43 MUm), inner
      nuclear + outer plexiform layers (INL + OPL; 0.36-1.04 MUm), and outer nuclear
      layers including photoreceptor segment (ONL + PR; 1.29-3.52 MUm) thicknesses.
      Limits of agreement for GCIP and ONL + PR thicknesses were narrow. Results of
      fully manual and computer-aided manual segmentation were comparable to those of
      fully automated segmentation. MS patients demonstrated macular RNFL, GCIP, and
      ONL + PR thinning compared to healthy controls across OCT segmentation
      techniques, irrespective of device (p < 0.03 for all). Low-contrast letter acuity
      in MS correlated significantly and more strongly with GCIP than peripapillary
      RNFL thicknesses, regardless of the segmentation method or device. GCIP and ONL +
      PR thicknesses, measured by different OCT devices and segmentation techniques,
      are reproducible and agree at the individual and cohort levels. GCIP thinning in
      MS correlates with visual dysfunction. Significant ONL + PR thinning, detectable
      across OCT segmentation techniques and devices, strongly supports ONL pathology
      in MS. Fully automated, fully manual and computer-assisted manual OCT
      segmentation techniques compare closely, highlighting the utility of accurate and
      time-efficient automated segmentation outcomes in MS clinical trials.

PMID- 22418996
TI  - Presymptomatic genetic testing in CADASIL.
AB  - Genetic counselling has been poorly investigated in cerebrovascular diseases.
      Characteristics, motivations and long-term outcome of presymptomatic tests (PT)
      in subjects at risk of CADASIL (Cerebral Autosomal Dominant Arteriopathy with
      Subcortical Infarcts and Leukoencephalopathy) were investigated at the National
      Centre for Rare Vascular Diseases of the Brain and/or Retina (CERVCO).
      Sociodemographic, motivational and psychological variables were collected between
      2003 and 2010 for PT applicants. Multidisciplinary consultations (with a
      geneticist, neurologist and psychologist) were proposed over a 6 month period.
      When PT showed a deleterious mutation of the NOTCH3 gene, cognitive performances,
      mood, autonomy and quality of life were also assessed. Over 7 years, only 33
      subjects asked for a PT of CADASIL. They were predominantly women, lived as a
      couple, had children and were of high sociocultural level. The dropout rate after
      the first step of the procedure was 63%. The characteristics of the 11 subjects
      who reached the end of the procedure did not differ from the 22 who dropped out.
      Six were carriers of the deleterious mutation and were still asymptomatic after a
      mean follow-up of 19 months. They did not experience any particular negative
      event and all of them indicated a high score of overall quality of life. Indeed,
      two carriers gave birth to their first child. These initial data in CADASIL show
      that PT is rarely requested and that there is a high dropout rate. Our study also
      highlights that a multidisciplinary and multistep procedure in genetic
      counselling testing appears useful to obtain minimal harmful consequences of
      genetic testing.

PMID- 22418998
TI  - Osmotic pellet system comprising osmotic core and in-process amorphized drug in
      polymer-surfactant layer for controlled delivery of poorly water-soluble drug.
AB  - The aim of the present investigation was to develop controlled porosity osmotic
      system for poorly water-soluble drug based on drug in polymer-surfactant layer
      technology. A poorly water-soluble drug, glipizide (GZ), was selected as the
      model drug. The technology involved core of the pellets containing osmotic agent
      coated with drug dispersed in polymer and surfactant layer, finally coated with
      release-retardant layer with pore former. The optimized drug-layer-coated pellets
      were evaluated for solubility of GZ at different pH conditions and characterized
      for amorphous nature of the drug by differential scanning calorimetry and X-ray
      powder diffractometry. The optimized release-retardant layer pellets were
      evaluated for in vitro drug release at different pH, hydrodynamic, and osmolality
      conditions. The optimized drug layer showed improvement in solubility (10 times
      in pH 1.2, 11 times in pH 4.5, and 21 times in pH 6.8), whereas pellets coated
      with cellulose acetate (15.0%, w/w, weight gain) with pore former triethyl
      citrate (10.0%, w/w, of polymer) demonstrated zero-order drug release for 24 h at
      different pH conditions; moreover, retardation of drug release was observed with
      increment of osmolality. This system could be a platform technology for
      controlled delivery of poorly water-soluble drugs.

PMID- 22418999
TI  - Percutaneous US-guided liver biopsy in focal lesions using a semiautomatic device
      allowing to perform multiple biopsies in a single-pass.
AB  - AIM: The aim of this study was to evaluate the safety and efficacy of
      percutaneous real-time ultra sound METHODS: One hundred and thirty-four
      consecutive percutaneous liver biopsies were performed in equal number of
      patients with focal liver lesions during a three-year period. All biopsies were
      performed with a single puncture, using a Tru-cat semiautomatic 18G needle
      (Precisa semi-automatic Tru-cut biopsy Device, HS Hospital Service, Italy) with
      removable inner stylet, under real-time US-guided. Two to five samples were
      obtained from each biopsy. In 12 cases an embolization of the biopsy track was
      performed. Thirty-two patients with hepatocellular carcinoma were followed for a
      period of 30-880 days for seeding. RESULTS: A total of 424 specimens were
      obtained from 134 biopsies. Evaluation of the biopsy specimens demonstrated that
      the 58.5% of them were >10 mm in length providing sufficient liver tissue for
      reliable histological diagnosis. The diagnosis was successful in 99.25% of the
      patients. No major complications or death occurred in our study group. Neither
      suspected nor confirmed tumor seeding was identified. CONCLUSION: Our results
      provide evidence that US-guided percutaneous liver biopsy using a semiautomatic
      18G Tru-Cut needle with removable inner stylet can be performed with safety and
      efficacy in patients with focal liver lesions. Further-more, there are strong
      indications that the use of an introducer that remains in position during
      multiple cutting needle passes, protects normal tissue along the track and
      minimizes "seeding" and bleeding complications.

PMID- 22419000
TI  - Correlation of Hepatitis B surface antigen mutations with clinical status of the
      chronically infected patients from Kermanshah, West of Iran.
AB  - AIM: Hepatitis B virus (HBV) genetic and protein variations have been found in
      chronic HBV infected patients who did not receive any treatment and active or
      passive immunizations. The aims of this study were to determine the genotypes as
      well as the patterns of variations distribution in chronically infected patients
      from the west part of Iran. METHODS: Forty-six people with chronic HBV infection
      were enrolled in the study. The surface genes were amplified, sequenced and
      subsequently aligned using international and national Iranian database. RESULTS:
      All strains belonged to genotype D, subgenotype D1 and subtype ayw2. Of all 116
      "mutations" that occurred at 59 nucleotide positions, 49 (42.2 %) were missense
      (amino acid altering) and 67 (57.7%) were silent (no amino acid changing),
      respectively. At the amino acid level, 38 (79.1%) out of 48 amino acid mutations
      occurred in different immune epitopes within the surface proteins, of which 2
      (5.2%) occurred in B cell; 12 (31.5%) in T helper and 24 (63.1%) inside CTL
      epitopes. There were significant associations between amino acid mutations
      (especially within immune epitopes) and anti-HBe positivity and increased ALT
      levels (P values: 0.014 and 0.04, respectively). CONCLUSION: The distribution of
      amino acid mutations as well as the ratio between silent and missense nucleotide
      mutations showed that a narrowly focused immune pressure had already been on the
      surface protein T cell epitopes (94.9% of mutations), particularly CTL epitopes
      which led to the emergence of escape mutants in these patients.

PMID- 22419001
TI  - Capturing patient reported outcomes and quality of life in routine clinical
      practice: ready for prime time?
AB  - AIM: Aim of the present study was to assess the feasibility of using internet
      tablets to capture patient reported outcomes (PRO) questionnaire in a busy
      gastroenterology clinic, and determine predictors of questionnaire completion.
      PRO and quality of life instruments are extensively used to estimate the burden
      of disease and as end-points in clinical trials. However, their collection by
      paper can be costly, prone to human errors, and inefficient. We hypothesized that
      the majority of patients, irrespective of age, gender or ethnicity, will be able
      to complete PRO questionnaires on Internet tablets in a timely manner with good
      levels of satisfaction. METHODS: Internet-enabled tablets were used to collect
      PRO, and summative scores of quality of life provided to physicians. Predictors
      of completion were first assessed univariately and then by multivariate analysis
      using automated stepwise selection method on 1,000 bootstrap samples. Patient
      satisfaction was assessed using 5 item Likert-like scale. RESULTS: During the 12
      week period, 1625 patient visits (mean age 49.8 +/- 14.3 years, females 55.2% and
      Whites 82.5%) entered PRO data into tablets, of which 1396 (85.9%) visits had
      complete response. Average completion time of PRO questionnaire was less than 10
      minutes (9.3 minutes +/- 7.0). Majority of the patients found tablets easy to use
      (69.7%) and preferred it over paper-based questionnaires (70.8%). Multivariate
      analysis showed that subjects who were white Caucasians (odds ratio [OR] 1.9;
      P=0.004), had higher Cleveland Clinic Global Quality of Life (OR 2.2; P=0.027),
      or had either IBD or liver disease, were more likely to complete questionnaire
      (OR 4.0; P=0.001). CONCLUSION: Collection of PROs in gastroenterology clinics
      using internet-tablets is feasible without any additional overhead, and with good
      levels of patient satisfaction and completion rates.

PMID- 22419002
TI  - Advanced HCC: emerging molecular therapies.
AB  - Hepatocellular carcinoma (HCC) is a common complication of chronic liver disease
      and represents the third-leading cause of death world-wide. While the majority of
      cases occur in Asia, the incidence has been rising in the West for some time.
      This is driven not only by the Hepatitis C epidemic but also the rising incidence
      of non-alcoholic steatohepatitis and resulting liver disease. Despite its
      frequency, treatments for HCC have generally been limited. Curative treatments
      are limited to surgical resection or liver transplant for a subset of patients
      and locally ablative techniques such as radiofrequency ablation (RFA) and trans
      arterial chemoembolization (TACE) have been shown to extend survival for patients
      with unresectable and intermediate stage liver cancer. For patients with advanced
      HCC, sorafenib, a small molecule multitargeted kinase inhibitor is the only agent
      that has been shown to improve survival. At this time there is an abundance of
      research activity in HCC with an emphasis on developing new agents that target
      specific molecular alterations in HCC. In this review, we will focus on those
      agents currently in Phase III studies for front-line, second-line and other
      indications.

PMID- 22419003
TI  - Pathways and gene expression profiles in hepatocellular carcinoma.
AB  - Hepatocarcinogenesis is a process attributed to progressive genomic changes which
      alter the hepatocellular phenotype producing cellular intermediates evolving into
      clearly neoplastic cells (hepatocellular carcinoma, HCC). During the
      preneoplastic phase, the liver is often the site of chronic hepatitis and/or
      cirrhosis, and this process leads to the production of monoclonal populations of
      aberrant and dysplastic hepatocytes that develop genetic and chromosomal
      alterations. At the moment three main molecular pathways of liver carcinogenesis
      have been described and several attempts of genetic classification of HCC have
      been proposed. The definition of genomic and molecular changes which occur during
      the development of HCC should improve the classification and prognostis of liver
      tumors. The development of sorafenib and other new targeted developing therapies
      were rendered possible by the discovery and understanding of the molecular and
      genetic pathogenesis of hepatocellular carcinoma. Besides viruses, such as
      Hepatitis B virus (HBV) and Hepatitis C virus (HCV), may contribute to cancer
      development by several ways; however, additional factors, such as host immunity
      and chronic inflammation and host cellular mutations also play a role in the
      transformation process. The understanding of these pathways will in the future
      enable the clinician to focus the treatment patients with HCC and customize
      single or combination therapy.

PMID- 22419004
TI  - Prevention of hepatocellular carcinoma: progress and challenges.
AB  - Hepatocellular carcinoma (HCC) is a lethal cancer for both men and women and is
      caused by multiple risk factors. Most patients with HCC have an underlying liver
      disease caused by either chronic viral infection due to hepatitis B or hepatitis
      C virus or non-viral etiologic risk factors such as alcohol, fatty liver disease,
      dietary aflatoxin exposure, smoking and diabetes mellitus. While these risk
      factors are progressively and persistently damaging the liver, the majority of
      patients show very few symptoms of HCC. By the time symptoms appear the cancer is
      typically at a very advanced stage with limited options for treatment. In order
      to prevent death from HCC, it is therefore critically important to reduce the
      prevalence of the major risk factors, identify and treat those at high risk for
      development of HCC, and institute effective surveillance strategies for early
      diagnosis and treatment of HCC. This article reviews the recent progress and
      current challenges to the prevention of HCC.

PMID- 22419005
TI  - Does antiviral therapy reduce the risk of hepatocellular carcinoma in patients
      with chronic hepatitis C?
AB  - Infection with the Hepatitis C virus (HCV) affects nearly 200 million people in
      the world. It is a leading cause of chronic hepatitis, cirrhosis and
      hepatocellular carcinoma (HCC). It is estimated that 25% of HCC worldwide is
      related to HCV, being the main cause in Western Europe, North America and Japan.
      HCV can be implicated in the development of HCC in an indirect way through
      induction of chronic inflammation, or directly by means of viral proteins
      activating several signaling pathways. For patients with clinically significant
      hepatic fibrosis there is widespread agreement that antiviral therapy is
      indicated in order to eliminate the virus. It is generally accepted that
      sustained virologic response (SVR), i.e. undetectable HCV RNA at 24 weeks after
      treatment withdrawal, is associated with resolution of liver disease in patients
      without cirrhosis. In the last decades, results of treatment for chronic
      hepatitis C have improved substantially. The current standard of care is a
      combination of pegylated interferon and ribavirin for 24 to 48 weeks, depending
      on the genotype. In the near future, this standard of care will include addition
      of directly-acting antivirals. In 2011 two protease inhibitors (boceprevir and
      telaprevir) have been registered for use in adults with genotype 1 chronic
      hepatitis C, increasing the SVR rates from less than 50% to about 70% in patients
      treated with a triple combination. There is limited evidence for the role of
      interferon-based therapy in primary, secondary and tertiary prophylaxis of HCC in
      patients with chronic Hepatitis C, as most studies were primarily designed to
      assess the antiviral effect of treatment and not the long-term impact on the
      natural history of the disease. Further prospective studies using the more
      successful emerging treatments of chronic hepatitis C are to be conducted to
      evaluate the risk of HCC.

PMID- 22419006
TI  - Anti-angiogenic therapy for HCC.
AB  - Hepatocellular carcinoma is an insidious disease that grows without eliciting
      pain. In the absence of surveillance, the diagnosis of hepatocellular carcinoma
      is usually made at a late stage, which excludes curative treatments and leaves
      patients with few therapeutic options. For years, conventional chemotherapy was
      administered but yielded poor results. This is not surprising since hepatocytes
      are well equipped to survive exposure to chemotherapeutics. Hepatocytes posses an
      extensive repertoire of enzymes and pumps capable of degrading and exporting
      these drugs. Bypassing hepatocytic tumor cells in favour of supportive cells
      represents an alternative treatment target that has achieved modest success. The
      supportive cells in the hepatic vasculature comprise endothelial cells and
      pericytes. Thanks to a concerted effort from fundamental and pharmacological
      researchers, several drugs targeted to the vasculature are reaching the clinic.
      This manuscript reviews the rationale for targeting the vascular cells to treat
      hepatocellular carcinoma, the signalling pathways underlying angiogenesis and the
      most promising drugs.

PMID- 22419008
TI  - Oxidative dehydrogenation of cyclohexene on size selected subnanometer cobalt
      clusters: improved catalytic performance via evolution of cluster-assembled
      nanostructures.
AB  - The catalytic activity of oxide-supported metal nanoclusters strongly depends on
      their size and support. In this study, the origin of morphology transformation
      and chemical state changes during the oxidative dehydrogenation of cyclohexene
      was investigated in terms of metal-support interactions. Model catalyst systems
      were prepared by deposition of size selected subnanometer Co(27+/-4) clusters on
      various metal oxide supports (Al(2)O(3), ZnO and TiO(2) and MgO). The oxidation
      state and reactivity of the supported cobalt clusters were investigated by
      temperature programmed reaction (TPRx) and in situ grazing incidence X-ray
      absorption (GIXAS) during oxidative dehydrogenation of cyclohexene, while the
      sintering resistance monitored with grazing incidence small angle X-ray
      scattering (GISAXS). The activity and selectivity of cobalt clusters shows strong
      dependence on the support. GIXAS reveals that metal-support interaction plays a
      key role in the reaction. The most pronounced support effect is observed for MgO,
      where during the course of the reaction in its activity, composition and size
      dynamically evolving nanoassembly is formed from subnanometer cobalt clusters.

PMID- 22419007
TI  - Risk assessment using a novel score to predict anastomotic leak and major
      complications after oesophageal resection.
AB  - BACKGROUND: Oesophagectomy is associated with significant morbidity and
      mortality. A simple score to define a patient's risk of developing major
      complications would be beneficial. METHODS: Patients who underwent upper
      gastrointestinal resections with an oesophageal anastomosis between 2005 and 2010
      were reviewed and formed the development dataset with resections performed in
      2011 forming a prospective validation dataset. The association between post
      operative C-reactive protein (CRP), white cell count (WCC) and albumin levels
      with anastomotic leak (AL) or major complication including death using the
      Clavien-Dindo (CD) classification were analysed by receiver operating
      characteristic curves. After multivariate analysis, from the development dataset,
      these factors were combined to create a novel score which was subsequently tested
      on the validation dataset. RESULTS: Two hundred fifty-eight patients were
      assessed to develop the score. Sixty-three patients (25%) developed a major
      complication, and there were seven (2.7%) in-patient deaths. Twenty-six (10%)
      patients were diagnosed with AL at median post-operative day 7 (range: 5-15). CRP
      (p = 0.002), WCC (p < 0.0001) and albumin (p = 0.001) were predictors of AL.
      Combining these markers improved prediction of AL (NUn score > 10: sensitivity
      95%, specificity 49%, diagnostic accuracy 0.801 (95% confidence interval: 0.692
      0.909, p < 0.0001)). The validation dataset confirmed these findings (NUn score >
      10: sensitivity 100%, specificity 57%, diagnostic accuracy 0.879 (95% CI 0.763
      0.994, p = 0.014)) and a major complication or death (NUn > 10: sensitivity 89%,
      specificity 63%, diagnostic accuracy 0.856 (95% CI 0.709-1, p = 0.001)).
      CONCLUSIONS: Blood-borne markers of the systemic inflammatory response are
      predictors of AL and major complications after oesophageal resection. When
      combined they may categorise a patient's risk of developing a serious
      complication with higher sensitivity and specificity.

PMID- 22419009
TI  - [Indications for different types of urinary diversion].
AB  - When urinary diversion is indicated, patient information concerning the
      advantages and disadvantages of different types of urinary diversion and their
      choices is of utmost importance for the functional outcome and patient
      satisfaction. There is a variety of choices for incontinent urinary diversion
      (ureterocutaneostomy, ileal conduit, colonic conduit) and continent urinary
      diversion (continent anal urinary diversion, continent cutaneous urinary
      diversion and urethral bladder substitution). In the individual case, the choices
      may be limited by patient criteria and/or medical criteria. Important patient
      criteria are preference, age and comorbidity, BMI, motivation, underlying disease
      and indication for cystectomy. Medical criteria which possibly limit choices of
      type of urinary diversion are kidney function/upper urinary tract status and
      limitations concerning the gastrointestinal tract, concerning urethra/sphincter
      as well as the ability and motivation to perform intermittent self
      catheterization. Preoperative information may use simulation of certain
      postoperative scenarios (urethral self-catheterization, fixation of water-filled
      conduit bags, holding test for anal liquids) to allow the individual patient to
      choose the optimal type of urinary diversion for his/her given situation from the
      mosaic of choices and possible individual limitations.

PMID- 22419010
TI  - [Symptomatic reflux and stenosis of ureteroenteric anastomosis. Diagnostics and
      therapy].
AB  - Stenosis of the ureteroenterostomy and symptomatic reflux are among the most
      dangerous complications of all forms of urinary diversion. Variations in ureter
      implantation techniques and different surgical expertises are responsible for the
      heterogeneity of the available prevalence data. Antirefluxive implantation
      techniques seem to be more vulnerable to stenosis and obstruction than refluxive
      techniques, although no difference in kidney function deterioration over time was
      shown according to the presence or absence of reflux protection. Despite frequent
      controls, approximately one quarter of all obstructed renal units show a complete
      loss of function. The reimplantation rate of stenotic ureters exceeds 30%.The
      development of an implantation stenosis may be silent and subtle. The loss of
      renal function often remains unnoticed if sonography and creatinine measurements
      are the only follow-up tools employed. Neither of these tests is reliable in
      estimating kidney function and may mislead both doctor and patient. DMSA
      scintigraphy and retrograde contrast studies (conduitogram, pouchogram) are the
      most sensitive tools available to evaluate a symptomatic reflux, whereas MAG-3
      renal scans and antegrade function tests (nephrostogram, renal pelvic pressure
      measurement) are recommended for investigating ureteric obstruction. Stenosis of
      the ureteroenterostomy usually occurs within 2 years after urinary diversion;
      delayed occurrence of ureteric obstruction is indicative of malignant local
      recurrence or compressive metastases.There are various minimally invasive
      treatment options such as balloon dilatation, internal ureterotomy, stenting and
      nephrostomy placement. However, the technical challenge of a ureteroenterostomy
      should not be a deterrent. In fact, if surgically possible, the patient should be
      offered open revision, since this is the only way to durably cure the underlying
      pathology and re-establish the already impaired quality of life of patients with
      urinary diversion as much as possible.

PMID- 22419011
TI  - [Patients' acceptance of urinary diversion. The pouch of Sisyphus].
AB  - It is important that any patient with a urinary diversion can accept the
      psychological impact alongside the surgical and physical aspects. However, there
      are currently no validated methods or instruments available to allow direct
      measurement of this phenomenon in these patients. Health-related quality of life
      (HRQoL) is often high following different types of urinary diversion-this may
      suggest a high acceptance level and thus may act as a secondary end point. Such
      an assessment is a retrospective validation of successful patient selection,
      allowing us to redirect the nihilistic misinterpretation that urologists should
      return to offering ileal conduits as a standard. In modern urinary diversion,
      high patient acceptance develops from comprehensive counselling providing a
      realistic expectation, careful patient-to-method-matching, strict adherence to
      surgical detail during the procedure and a meticulous lifelong follow-up. Coping
      strategies, disease-related social support and confidence in the success of
      treatment are among other factors which contribute to acceptance of urinary
      reconstruction as either independent or combined factors. Significant experience
      is required in every respect, as misjudgement and mistakes in any of these issues
      may be detrimental to the patients' health. It should be acknowledged that there
      is no 'best' urinary diversion in general terms. A reconstructive surgeon must
      have all techniques available and choices need to be tailored to the individual
      patient.

PMID- 22419012
TI  - [Homeopathic prophylaxis of urinary tract infections in patients with neurogenic
      bladder dysfunction].
AB  - Recurrent urinary tract infections (UTI) in patients with spinal cord injury are
      a frequent clinical problem. Often, preventive measures are not successful. We
      present the case reports of five patients with recurrent UTI who received
      additional homeopathic treatment. Of these patients, three remained free of UTI,
      whereas UTI frequency was reduced in two patients. Our initial experience with
      homeopathic prevention of UTI is encouraging. For an evidence-based evaluation of
      this concept, prospective studies are required.

PMID- 22419013
TI  - Insidious role of nitric oxide in migration/invasion of colon cancer cells by
      upregulating MMP-2/9 via activation of cGMP-PKG-ERK signaling pathways.
AB  - Nitric oxide (NO), an uncharged free radical is implicated in various
      physiological and pathological processes. The present study is an investigation
      on the effect of NO on proliferation, apoptosis and migration of colon cancer
      cells. Colon adenocarcinoma cells, WiDr, were used for the in vitro experiments.
      Tissues from colon adenocarcinoma, adjacent normal and inflammatory tissue and
      lymph node with metastasis were evaluated for iNOS, MMP-2/9 and Fra-1/Fra-2. NO
      increases the proliferation of cancer cells and simultaneously prevents
      apoptosis. Expression of MMP-2/9, RhoB and Rac-1 was enhanced by NO in a time
      dependent manner. Further, NO increased phosphorylation of ERK1/2 and induced
      nuclear translocation of Fra-1 and Fra-2. Electrophoretic mobility shift analysis
      and use of deletion mutant promoter constructs identified role of AP-1 in NO
      mediated regulation of MMP-2/9. iNOS, MMP-2/9, Fra-1 and Fra-2 in normal and
      colon adenocarcinoma tissues were analyzed and it was found that increased
      expression of these proteins in cancer when compared to normal provides support
      to our in vitro findings. The study showed that the NO-cGMP-PKG promotes MMP-2/9
      expression by activating ERK-1/2 and AP-1. This study reveals the insidious role
      of NO in imparting tumor aggressiveness.

PMID- 22419014
TI  - Kinetic model for solid-state degradation of gabapentin.
AB  - Gabapentin degrades directly to gabapentin-lactam (gaba-L) in the solid state.
      The objective of this study was to formulate a drug degradation model that
      accounted for the environmental storage conditions and mechanical stress (prior
      to storage) on lactamization kinetics. The effects of mechanical stress on drug
      degradation kinetics were determined by milling gabapentin in a FRITSCH Planetary
      Micro Mill for 0 and 60 min. The resultant gabapentin powder was stored at 40 
      degrees C-60  degrees C and 5%-30% relative humidity. The rate of gaba-L
      formation was measured by high-performance liquid chromatography. An irreversible
      two-step autocatalytic reaction scheme was fit using nonlinear regression
      methods. The resultant kinetic model was used to predict the time-dependent
      concentration of degradant of gabapentin tablets prepared under various exemplary
      manufacturing conditions, thereby demonstrating the ability of the model to link
      manufacturing variation and chemical stability in solid-state gabapentin
      formulations.

PMID- 22419015
TI  - Inositol-requiring protein 1alpha signaling pathway is activated in the temporal
      cortex of patients with mesial temporal lobe epilepsy.
AB  - Accumulating evidence suggests that repeated seizures could induce endoplasmic
      reticulum (ER) stress. Inositol-requiring protein 1alpha (IRE1alpha) is a vital
      pro-apoptotic molecule in ER stress, but it remains unclear whether the signaling
      pathway mediated by IRE1alpha is involved in human temporal lobe epilepsy. In
      this report, we investigated IRE1alpha-mediated ER stress pro-apoptotic signaling
      pathway in resected anterior temporal neocortex from 32 patients with intractable
      mesial temporal lobe epilepsy by immunofluorescence and western blot analysis.
      Our results indicate that chronic epilepsy induces ER stress, and IRE1alpha
      mediated ER stress apoptotic signaling pathway is involved in brain damage after
      repeated seizures, which may provide a new therapeutic target to prevent brain
      damage caused by epilepsy.

PMID- 22419016
TI  - A case with anti-galactocerebroside antibody-positive Mycoplasma pneumoniae
      meningoencephalitis presenting secondary hypersomnia.
AB  - Galactocerebroside (Gal-C) is a major myelin component in the central nervous
      system. The anti-Gal-C antibody induced by mycoplasma infection may therefore be
      involved in the pathogenic mechanisms of mycoplasma-associated encephalitis. Here
      we report an adult case of mycoplasma encephalitis developing excessive daytime
      sleepiness. Brain MRI suggested that hypothalamic involvement was compatible with
      hypersomnia. This finding was corroborated by decreased hypocretin-1 in
      cerebrospinal fluid (CSF) and the manifestation of diabetes insipidus. Screening
      for anti-glycolipid antibody profiles showed the selective increase of serum anti
      Gal-C antibody. After treatment with minocyclin, the patient's daytime sleepiness
      was markedly improved and the CSF hypocretin-1 level became almost normal, as
      well. It is known that CSF hypocretin-1 is decreased in Guillain-Barre syndrome
      mediated by anti-glycolipid antibody, suggesting a possible mechanistic link
      between anti-glycolipid antibodies and hypothalamic involvement. The present case
      further emphasizes the broad spectrum of neurological complications after
      mycoplasma infection.

PMID- 22419017
TI  - Delayed ischemic stroke associated with bromocriptine-induced reversible cerebral
      vasoconstriction syndrome.

PMID- 22419018
TI  - Intranasal administration: a potential solution for cross-BBB delivering
      neurotrophic factors.
AB  - Neurotrophic factors (NTFs) are endogenous polypeptides that regulate the growth,
      survival, differentiation, and functioning of neurons. The neuroprotective
      effects of NTFs in experimental animals give strong rationale for developing
      therapies for neurological disorders. However, when NTFs are applied in clinical
      trials, great expectation leads to equal disappointment. NTFs are large molecular
      weighted and hydrophilic proteins, which limits their access to the central
      nervous system (CNS) after systemic administration, principally due to poor blood
      brain barrier (BBB) permeability and unfavorable pharmacokinetic profiles.
      Although intracerebral infusion may transport NTFs into the CNS, the invasiveness
      limits its clinical application. Intranasal administration has been under
      research for decades and presents promising outcomes in preclinical studies for
      brain delivering of NTFs. After intranasal delivery, NTFs gain direct and quick
      access into the CNS at concentrations high enough to elicit their biological
      effects, bypassing the BBB and minimizing systemic exposure. Due to its
      invasiveness and convenience, intranasal delivery is feasible for NTFs
      administration. Although direct evidence of nose-to-brain pathway in human is
      lacking due to ethical problems, the existence of the nose-to-cerebral spinal
      fluid pathway has been verified in men. Furthermore, there is abundant indirect
      evidence for the nose-to-brain pathway as determined by the efficacy of
      intranasally administered neuroproteins, such as insulin, oxytocin, and
      vasopressin in clinical trials. Based on the solid preclinical research
      supporting the efficacy of intranasal NTFs, and the successful clinical
      application of neuroproteins (not NTFs), it is time to evaluate clinical
      application of NTFs in treating both acute and chronic CNS diseases.

PMID- 22419019
TI  - Activation of alternative pathways of angiogenesis and involvement of stem cells
      following anti-angiogenesis treatment in glioma.
AB  - Malignant gliomas are hypervascular tumors that are highly resistant to all the
      currently available multimodal treatments. Therefore, anti-angiogenic therapies
      targeting VEGF or VEGF receptors (VEGFRs) were designed and thought to be an
      effective tool for controlling the growth of malignant gliomas. However, recent
      results of early clinical trials using humanized monoclonal antibodies against
      VEGF (Bevacizumab), as well as small-molecule tyrosine kinase inhibitors that
      target different VEGF receptors (VEGFRs) (Vatalanib, Vandetanib, Sunitinib,
      Sorafenib, etc) alone or in combination with other therapeutic agents
      demonstrated differing outcomes, with the majority of reports indicating that
      glioma developed resistance to the employed anti-angiogenic treatments. It has
      been noted that continued anti-angiogenic therapy targeting only the VEGF-VEGFR
      system might affect pro-angiogenic factors other than VEGF, such as basic
      fibroblast growth factor (bFGF), stromal derived factor 1 (SDF-1) and Tie-2.
      These factors may in turn stimulate angiogenesis by mobilizing bone marrow
      derived precursor cells, such as endothelial progenitor cells (EPCs), which are
      known to promote angiogenesis and vasculogenesis. In this short review, the
      current antiangiogenic treatments, possible mechanisms of activation of
      alternative pathways of angiogenesis, and possible involvement of bone marrow
      derived progenitor cells in the failure of anti-angiogenic treatments are
      discussed.

PMID- 22419020
TI  - Role of angiogenesis on bone formation.
AB  - Angiogenesis and bone formation are coupled during skeletal development and
      fracture healing. This relationship, although known for some time, has not been
      properly explored. Advances in the discovery of how angiogenesis is regulated in
      physiological processes like embryogenesis, endometrial regeneration and wound
      healing or in pathologies such as cancer have provided a deeper understanding of
      how angiogenic factors may interact with bone cells to improve bone formation and
      bone regeneration. The lack of oxygen (hypoxia) and the subsequent generation of
      angiogenic factors have been shown to be critical in the development of a regular
      skeleton and achieving successful bone regeneration and fracture healing. Given
      that vascular status is important for a proper bone homeostasis, defining the
      roles of osteoblasts, osteoclasts, endothelial cells and angiogenic factors and
      their interactions in bone is a key issue for the development of new strategies
      to manage bone pathologies and nonfused fractures.

PMID- 22419021
TI  - High mobility group A1 and cancer: potential biomarker and therapeutic target.
AB  - The High Mobility Group A1 (HMGA1, formerly HMG-I/Y) gene is highly expressed
      during embryogenesis and in virtually all aggressive human cancers studied to
      date, although its role in these settings is only beginning to emerge. Moreover,
      high levels of expression portend a poor prognosis in some tumors. Increasing
      evidence suggests that the HMGA1 protein functions as a master regulator with a
      critical role in normal development and tumor progression in diverse
      malignancies. These proteins contain AT-hook DNA binding domains that mediate
      binding to AT-rich regions of chromatin. After binding to DNA, HMGA1 alters DNA
      structure, and orchestrates the assembly of a transcriptional complex or
      "enhanceosome" to regulate gene expression. Previous studies indicate that HMGA1
      participates in regulating fundamental cellular processes, including
      transcription, cell cycle progression, embryonic development, neoplastic
      transformation, differentiation, senescence, viral integration, and DNA repair by
      virtue of its ability to interact with other proteins, bind to DNA, and modulate
      gene expression. Recent studies also link HMGA1 expression to poor
      differentiation status and a refractory, stem cell-like state in aggressive
      cancers. Together, these findings suggest that HMGA1 could serve as a useful
      biomarker and therapeutic target in advanced malignancies. Here, we focus on
      prior studies implicating HMGA1 in the pathogenesis of refractory human tumors
      arising from diverse tissues and its potential role as a biomarker. We also
      review previous attempts to target HMGA1 pathways in cancer. Further study of
      HMGA1 promises to have a major impact on our ability to understand and treat
      cancer.

PMID- 22419022
TI  - Correlation of epithelial-mesenchymal transition markers with clinicopathologic
      parameters in adenocarcinomas and squamous cell carcinoma of the lung.
AB  - Epithelial-mesenchymal transition (EMT) is characterized by the loss of
      epithelial cell junction proteins and the gain of mesenchymal markers. The aim of
      this study was to analyze the associations between the EMT-related markers
      vimentin, E-cadherin, beta-catenin, slug, snail, and twist1 and clinicopathologic
      parameters as well as epidermal growth factor receptor (EGFR) gene copy number
      and protein expression in non-small cell lung carcinoma (NSCLC). Fifty-nine
      squamous cell carcinomas (SCC) and 43 adenocarcinomas (AD) were
      immunohistochemically examined for respective EMT markers and for EGFR, using the
      EGFR PharmDx kit (Dako) for protein expression and automated silver enhanced in
      situ hybridization (SISH) for copy number. Vimentin expression in tumor epithelia
      was significantly higher in AD samples than in SCC samples (P=0.015). Among AD
      samples, vimentin expression was positively correlated with histologic grade (2
      vs. 3; P=0.021) and exhibited a tendency toward a positive correlation with pTNM
      stage (I vs. II-IV; P=0.052). EGFR gene copy number was positively correlated
      with EGFR protein expression among both AD samples (P=0.008) and SCC samples
      (P=0.042), with EGFR protein expression being significantly higher in SCC samples
      compared with AD (P=0.038). Among AD samples, EGFR protein expression was
      associated with higher cytoplasmic expression of beta-catenin (P=0.031). Among
      SCC samples, EGFR protein expression was negatively correlated with nuclear
      expression of beta-catenin (P=0.033) but positively with nuclear slug (P=0.021).
      The expression pattern of EMT markers in AD suggests that vimentin is a possible
      immunohistochemical predictor of tumor progression.

PMID- 22419023
TI  - Prognostic significance of BAF57 expression in patients with endometrial
      carcinoma.
AB  - This study was conducted to elucidate the prognostic significance of BAF57 in
      patients with endometrial carcinoma. We investigated the relationship between the
      immunohistochemical expression of BAF57 and various clinicopathological variables
      in 111 endometrial carcinomas. Both univariate and multivariate regression
      analyses were performed. The correlations between the BAF57 expression and the
      other variables including estrogen receptor (ER) and p53 were examined. The high
      nuclear BAF57 expression was detected in 42 (37.8%) endometrial carcinomas, and
      69 (62.2%) endometrial carcinomas were defined as having low nuclear BAF57
      expression. The BAF57 expression was significantly associated with the surgical
      stage, grade of the tumor, myometrial invasion, lympho-vascular space invasion
      (LVSI) and lymph node metastasis. The 10-year overall survival rates of patients
      with low and high BAF57 expression were 96.9% and 58.2%, respectively (p<0.001).
      A multivariate analysis identified BAF57 expression as an independent prognostic
      factor. The BAF57 expression was significantly correlated with p53 expression
      (r=0.312, P=0.001), but was not correlated with ER expression (r= -0.141,
      P=0.14). The high BAF57 expression is an independent marker of poor prognosis of
      the patients in endometrial carcinomas. The inhibition of BAF57 activity may be
      one of the candidates for endometrial cancer therapy, especially therapy for
      aggressive tumors showing overexpression of p53.

PMID- 22419024
TI  - Expression of platelet-derived growth factor and its receptors in spontaneous
      canine hemangiosarcoma and cutaneous hemangioma.
AB  - Hemangiosarcoma (HSA) is a malignant neoplasia of vascular endothelial cells
      (ECs). Our previous report on the expression of vascular endothelial growth
      factor, basic fibroblast growth factor, and their receptors in canine HSA
      suggested an autocrine/ paracrine mechanism of tumor growth. However, the
      influence of other angiogenic growth factors in canine HSA was not elucidated;
      therefore, the expression of platelet-derived growth factor (PDGF) and its
      receptors was investigated by immunohistochemical analysis. Forty-six canine HSAs
      and 21 canine cutaneous hemangiomas (HAs) were analyzed. For
      immunohistochemistry, anti-PDGF-BB, anti-PDGFR-alpha, and anti-PDGFR-beta
      antibodies were utilized as primary antibodies. Immunoreactivities were scored as
      strongly positive (>25% positive neoplastic cells), weakly positive (1-25%
      positive neoplastic cells), and negative if not staining at all. In cutaneous HA,
      33.3% and 57.1% of cases were strongly and weakly positive, respectively, and
      43.5% and 13.0% of HSAs were strongly and weakly positive for PDGF-BB,
      respectively. Moreover, 38.1% and 28.6% of cutaneous HAs cases were strongly and
      weakly positive, respectively, and 23.9% and 4.3% of HSAs cases were strongly and
      weakly positive, respectively, for PDGFR-alpha. Thirty-five HSAs cases (76.1%)
      were strongly positive, and the remaining 11 (23.9%) were weakly positive for
      PDGFR-beta. In contrast, 18 (72.0%) cutaneous HAs were negative, and only 3 cases
      (12.0%) were weakly positive, for PDGFR-beta. The proportion of strongly positive
      cases of HSAs was significantly higher than that of cutaneous HA for PDGFR-beta
      (P<0.01), while PDGFR-alpha was highly expressed in cutaneous HA and may be
      related to pathogenesis of cutaneous HA. Therefore, PDGFR-beta may be associated
      with the malignant nature of canine HSA.

PMID- 22419025
TI  - Semiquantitative analysis of ECM molecules in the different cartilage layers in
      early and advanced osteoarthritis of the knee joint.
AB  - The study was conducted to examine the expression of collagen type I and II in
      the different cartilage layers in relation to other ECM molecules during the
      progression of early osteoarthritic degeneration in human articular cartilage
      (AC).  Quantitative real-time (RT)-PCR and colorimetrical techniques were used
      for calibration of Photoshop-based image analysis in detecting such lesions. 
      Immunohistochemistry and histology were performed with 40 cartilage tissue
      samples showing mild (ICRS grade 1b) respectively moderate/advanced (ICRS grade
      3a or 3b) (20 each) osteoarthritis compared with 15 healthy biopsies.
      Furthermore, we quantified our results on the gene expression of collagen type I
      and II and aggrecan with the help of real-time (RT)-PCR. Proteoglycan content was
      measured colorimetrically. The digitized images of histology and
      immunohistochemistry stains were analyzed with Photoshop software. T-test and
      Spearman correlation analysis were used for statistical analysis.  In the
      earliest stages of AC deterioration the loss of collagen type II was associated
      with the appearance of collagen type I, shown by increasing amounts of collagen
      type I mRNA. During subsequent stages, a progressive loss of structural integrity
      was associated with increasing deposition of collagen type I as part of a natural
      healing response. A decrease of collagen type II is visible especially in the
      upper fibrillated area of the advanced osteoarthritic samples, which then leads
      to an overall decrease. Analysis of proteoglycan showed losses of the overall
      content and a loss of the classical zonal formation. Correlation analysis of the
      proteoglycan Photoshop measurements with the RT-PCR revealed strong correlation
      for Safranin O and collagen type I, medium for collagen type II, alcian blue and
      glycoprotein but weak correlation with PCR aggrecan results.   Photoshop based
      image analysis might become a valuable supplement for well known
      histopathological grading systems of lesioned articular cartilage.  The evidence
      of collagen type I production early in the OA disease process coupled with the
      ability of chondrocytes to up-regulate collagen type II production suggests that
      therapeutic agents that suppress collagen type I production and increase collagen
      type II production may enable chondrocytes to generate a more effective repair
      response.

PMID- 22419026
TI  - Expression of the RNA-binding protein HuR and its clinical significance in human
      stage I and II lung adenocarcinoma.
AB  - The ubiquitously expressed RNA-binding protein Hu antigen (HuR) participates in
      the post-transcriptional regulation of mRNAs bearing U- and AU-rich sequences.
      Expression of HuR is increased in cancers of the breast, colon, ovary and lung
      and cytoplasmic immunoreactivity for HuR was found to be closely related to poor
      outcomes in patients with these tumors.  Since the regulation of HuR function is
      closely linked to its subcellular localization, we evaluated, by quantitative
      immunohistochemistry, the impact on clinical outcome of both nuclear and
      cytoplasmic levels (integrated density: ID) of HuR and of nuclear/cytoplasmic
      ratio (N/C) in 54 lung adenocarcinomas from stage I and II patients.  Nuclear and
      cytoplasmic Hur IDs and N/C were not associated with age, smoking or tumor
      diameter. Low N/C was significantly associated with lymph-node involvement at
      presentation. Cox's regression analysis showed that high cytoplasmic, but not
      nuclear, HuR ID and low N/C were directly associated with the risk of death and
      metastasis. In the multivariate analysis, low HuR N/C retained an independent
      negative prognostic significance relative to the risk of metastasis and death.
      Moreover, the levels of N/C allowed us to discriminate subjects with the highest
      risk of metastasis and death among patients with lung adenocarcinomas expressing
      high levels of cytoplasmic HuR.  In conclusion, the measure of the ratio between
      nuclear and cytoplasmic HuR levels allows a sensitive prognostic evaluation of
      the clinical outcome in early stage lung adenocarcinoma patients.

PMID- 22419027
TI  - Genistein stimulates the hypothalamo-pituitary-adrenal axis in adult rats:
      morphological and hormonal study.
AB  - Genistein, the soy isoflavone structurally similar to estradiol, is widely
      consumed for putative beneficial health effects. However, there is a lack of data
      about the genisteins' effects in adult males, especially its effects on the
      hipothalamo-pituitary-adrenal (HPA) axis. Therefore, the present study was
      carried out to investigate the effects of genistein on the HPA axis in
      orchidectomized adult rats, and to create a parallel with those of estradiol.
      Changes in the hypothalamic corticotrophin-releasing hormone (CRH) neurons and
      pituitary corticotrophs (ACTH cells) were evaluated stereologically, while
      corticosterone and ACTH levels were determined biochemically. Orchidectomy (Orx)
      provoked the enlargement (p<0.05) of: hypothalamic paraventricular nucleus volume
      (60%), percentage of CRH neurons (23%), percentage of activated CRH neurons
      (45%); pituitary weight (15%) and ACTH level (57%). In comparison with Orx,
      estradiol treatment provoked the enlargement (p<0.05) of: percentage of CRH
      neurons (28%), percentage of activated CRH neurons (2.7-fold), pituitary weight
      (131%) and volume (82%), ACTH level (69%), the serum (103%) and adrenal tissue
      (4.8 fold) level of corticosterone. Clearly, Orx has induced the increase in HPA
      axis activity, which even augments after estradiol treatment. Also, compared to
      Orx, genistein treatment provoked the enhancement (p<0.05) of: percentage of
      activated CRH neurons (2.3-fold), pituitary weight (28%) and volume (21%), total
      number of ACTH cells (22%) ACTH level (45%), the serum (2.6-fold) and adrenal
      tissue (2.8 fold) level of corticosterone. It can be concluded that an identical
      tendency, concerning the HPA axis parameters, follows estradiol and genistein
      administration to the orchidectomized adult rats.

PMID- 22419028
TI  - FAP-related desmoid tumors: a series of 44 patients evaluated in a cancer
      referral center.
AB  - Desmoid tumors (DTs), the commonest extra-intestinal manifestation of familial
      adenomatosis polyposis (FAP), are monoclonal neoplasms demonstrating fibroblastic
      - myofibroblastic differentiation; they are locally invasive without metastatic
      capacity. FAP-associated DT natural history knowledge is limited; we examined
      patient and tumor characteristics for a FAP-DT cohort and evaluated anti-DT
      therapy molecular target expression levels (immunohistochemical analyses, FAP-DT
      tissue microarray; TMA). Forty-four patients were classified as intra-abdominal
      (IA; n=26), abdominal wall (AW)/extra-abdominal (EA; n=12) or concomitant IA/AW
      (n=6) based on DT primary diagnosis location. Positive family histories were
      found in 62% of FAP versus 10% of DT patients. Surgery was the mainstay therapy
      for AW/EW patients, whereas IA DTs received surgery, chemotherapy, radiotherapy,
      tamoxifen, NSAIDs, and/or imatinib. Eight of 20 completely resected DTs in the IA
      and AW/EA groups recurred; 12 of 38 patients in these groups (33%) developed
      secondary lesions elsewhere. Two intestinal mesenteric DT patients died of
      disease, three from other cancers, 27 are alive with disease and 12 are alive
      without disease. All evaluable FAP-DT exhibited nuclear beta-catenin, 65% were
      positive for cyclin D1, and 66% expressed nuclear p53. No ERalpha expression was
      observed, but ERbeta was expressed in 72%. COX2 was expressed in all evaluable
      FAP-DTs. KIT was rarely found in DTs but both PDGFRs and their ligands were
      expressed. Comparing biomarker expression (IA vs. EA DTs), only nuclear ER-beta
      staining was significantly higher in EA lesions (p=0.0070); no other markers were
      site informative. Enhanced knowledge of FAP-DT molecular underpinnings will
      facilitate development of novel therapeutic strategies.

PMID- 22419029
TI  - Poly(ADP-ribose) in the skin and in melanomas.
AB  - Cutaneous melanoma (CM) and uveal melanoma (UM) represent the most aggressive
      pigment cell tumor types. Our investigation examined the signaling molecule
      poly(ADP-ribose) (PAR) in CM and UM. We have demonstrated PAR in keratinocytes,
      sebocytes, hair follicles, endothelial cells and in subcutaneous adipocytes in
      the normal skin indicating that PAR may regulate physiological functions in these
      cell types. Furthermore, CM cells were PAR positive and tumor invasion
      level/thickness of CM correlated with the PAR content of the cell nuclei, with
      higher Clark and Breslow indices and AJCC scores associating with higher PAR
      content. This correlation was especially marked in the samples of female
      patients. In UM tumors (n=12) a slight overall and strong perivascular PAR
      staining was observed with considerable individual variations. In view of recent
      successful clinical trials with PARP inhibitors as adjuvant chemotherapeutic
      agents, our results suggest that melanomas may display differential sensitivity
      towards this novel therapeutic modality which should be considered for the
      selection of patients.

PMID- 22419030
TI  - Calcium phosphate cement delivering zoledronate decreases bone turnover rate and
      restores bone architecture in ovariectomized rats.
AB  - Patients sustaining bony fractures frequently require the application of bone
      graft substitutes to fill the bone defects. In the meantime, anti-osteoporosis
      drugs may be added in bone fillers to treat osteoporosis, especially in
      postmenopausal women and the elderly. The effects of zoledronate-impregnated
      calcium phosphate cement (ZLN/CPC) on ovariectomized (OVX) rats were evaluated.
      OVX rats were implanted with ZLN/CPC, containing 0.025 mg ZLN in the greater
      omentum. Afterward the clinical sign of toxicity was recorded for eight weeks.
      The rats were sacrificed and blood samples were collected for hematology and
      serum bone turnover markers analyses. The four limbs of the rats were harvested
      and micro-computer tomography (micro-CT) scanning and bone ash analyses were
      performed. No clinical toxicity was observed in the treated rats. Compared to the
      OVX rats, levels of bone resorption markers (fragments of C-telopeptides of type
      I collagen) and bone formation markers (alkaline phosphatase and osteocalcin)
      decreased significantly in the treated rats. Osteopontin, which mediates the
      anchoring of osteoclasts to the mineral matrix of bones, also decreased
      significantly. Micro-CT scanning and histologic examinations of the distal
      femoral metaphyses showed that the cancellous bone architectures were restored,
      with a concomitant decrease in bone porosity. The bone mineral content in the
      bone ashes also increased significantly. This study indicates that ZLN
      impregnated CPC reduces bone turnover rate and restores bone architecture in OVX
      rats. CPC may be an appropriate carrier to deliver drugs to treat osteoporosis,
      and this approach may also reduce rates of post-dosing symptoms for intravenous
      ZLN delivery.

PMID- 22419031
TI  - Narciclasine as well as other Amaryllidaceae isocarbostyrils are promising GTP
      ase targeting agents against brain cancers.
AB  - The anticancer activity of Amaryllidaceae isocarbostyrils is well documented. At
      pharmacological concentrations, that is, approximately 1 MUM in vitro and
      approximately 10 mg/kg in vivo, narciclasine displays marked proapoptotic and
      cytotoxic activity, as does pancratistatin, and significant in vivo anticancer
      effects in various experimental models, but it is also associated with severe
      toxic side effects. At physiological doses, that is, approximately 50 nM in vitro
      and approximately 1 mg/kg in vivo, narciclasine is not cytotoxic but cytostatic
      and displays marked anticancer activity in vivo in experimental models of brain
      cancer (including gliomas and brain metastases), but it is not associated with
      toxic side effects. The cytostatic activity of narciclasine involves the
      impairment of actin cytoskeleton organization by targeting GTPases, including
      RhoA and the elongation factor eEF1A. We have demonstrated that chronic
      treatments of narciclasine (1 mg/kg) significantly increased the survival of
      immunodeficient mice orthotopically xenografted with highly invasive human
      glioblastomas and apoptosis-resistant brain metastases, including melanoma- and
      non-small-cell-lung cancer- (NSCLC) related brain metastases. Thus, narciclasine
      is a potentially promising agent for the treatment of primary brain cancers and
      various brain metastases. To date, efforts to develop synthetic analogs with
      anticancer properties superior to those of narciclasine have failed; thus,
      research efforts are now focused on narciclasine prodrugs.

PMID- 22419033
TI  - Electrophilicity of alpha-oxo gold carbene intermediates: halogen abstractions
      from halogenated solvents leading to the formation of chloro/bromomethyl ketones.
AB  - alpha-Oxo gold carbenes generated via intermolecular oxidation of terminal
      alkynes are shown to be highly electrophilic and can effectively abstract halogen
      from halogenated solvents such as 1,2-dichloroethane or 1,2-dibromoethane.
      Chloro/bromomethyl ketones are prepared in moderate efficiencies in one step
      using Ph(3)PAuNTf(2) as the catalyst and 8-methylquinoline N-oxide as the
      oxidant.

PMID- 22419034
TI  - Increased aquaporin-1 and Na+ -K+ -2Cl- cotransporter 1 expression in choroid
      plexus leads to blood-cerebrospinal fluid barrier disruption and necrosis of
      hippocampal CA1 cells in acute rat models of hyponatremia.
AB  - Hyponatremia is a metabolic disorder characterized by increased cerebrospinal
      fluid (CSF) volume and pressure, although the site of brain insult is unclear.
      Specifically, the hippocampus, which is in direct contact with expanding CSF
      ventricles, may be involved. The present study was undertaken to investigate the
      possible roles of choroid plexus aquaporin-1 (AQP1) and of cation chloride
      transporters (Na(+) -K(+) -2Cl(-) cotransporter 1 [NKCC1] and K(+) -Cl(-)
      cotransporter 4 [KCC4]) in the underlying hippocampal pathophysiology of
      hyponatremia in acute (6 and 12 hr duration) experimental models. It was found
      that the expressions of AQP1 and NKCC1 proteins in choroid plexus were
      significantly increased, whereas the expression of KCC4 protein was unchanged vs.
      control values after 6 and 12 hr of hyponatremia. Choroid plexuses with increased
      AQP1 and NKCC1 after 6 hr of hyponatremia showed caspase 3-dependent apoptosis
      and disruption of the blood-CSF barrier. Furthermore, necrotic changes in CA1
      neuronal cells were observed after 6 and 12 hr of hyponatremia. Overall, these
      data suggest that increases in AQP1 and NKCC1 expression under hyposmotic stress
      may be one of the molecular mechanisms underlying the pathophysiology of acute
      hyponatremia, such as the necrotic cell death of hippocampal CA1 region by
      increasing water transport across the blood-CSF barrier. Furthermore, we suggest
      that opening of the blood-CSF barrier after acute hyponatremia may be triggered
      the secondary adverse conditions that are capable of enhancing selective necrosis
      in hippocampal CA1 cells.

PMID- 22419035
TI  - Morphometric analysis of postoperative corneal neovascularization after high-risk
      keratoplasty: herpetic versus non-herpetic disease.
AB  - BACKGROUND: Postoperative complications after high-risk corneal grafting are
      decisively associated with corneal neovascularization (CNV). This study aimed to
      identify the incidence, extent, speed, localization, and influence of surgery
      related factors on CNV after high-risk penetrating keratoplasty (PK) and to
      evaluate the effect of removing the angiogenic stimulus, i.e., residual
      components of herpes simplex virus (HSV) on postkeratoplasty CNV in patients with
      herpetic stromal keratitis (HSK). METHODS: All primary high-risk PK performed for
      HSK and non-herpetic keratitis (controls) between 1 January 1998 and 31 December
      2003 at our department with available standardized corneal photographs taken
      preoperatively as well as 6 weeks, 3, 6 and 12 months postoperatively were
      evaluated (n (herpes) = 19, n (controls) = 5 patients). Maximal extension of CNV,
      limbus suture distance (LSD), limbus graft distance (LGD) and graft size in
      digitalized pictures were measured in each of the 16 sectors of the cornea at
      every visit. RESULTS: One hundred percent of the prevascularized corneas (n = 24)
      showed further CNV outgrowth within 1 year after keratoplasty, while 58 % of
      these patients featured high-grade CNV reaching the host-graft junction or
      invading the donor tissue. Overall, CNV outgrowth was fastest during the first 6
      weeks after PK, with a mean speed of 48 MUm/week. Mean CNV growth speed within 6
      months post-PK was significantly lower in the herpes group (13 MUm/week) than in
      the non-herpes group (25 MUm/week, p = 0.017). Corneal location around the 12
      o'clock position showed the most intense vessel outgrowth, which proved to be an
      independent risk factor for high-grade CNV (p = 0.025). Inverse correlation was
      evident between CNV growth speed and LSD (p = 0.032). CONCLUSIONS: Additional
      intense CNV outgrowth is a common phenomenon after high-risk keratoplasty,
      strongly marked in the early postoperative period. The removal of residual HSV
      components representing a potential angiogenic stimulus leads to a reduction in
      corneal angiogenesis not in the short term, but in the long term after PK in
      patients with HSK. In addition to preferable atraumatic operation techniques,
      modern antiviral prophylaxis and anti-angiogenic therapy should be applied early,
      possibly even prior to transplantation. Short LSD seems to be an intraoperative
      adjustable risk factor for CNV in high-risk setting. Attention should also be
      paid to the superior site around the 12 o'clock position.

PMID- 22419036
TI  - In-vivo and ex-vivo characterization of laser-induced choroidal
      neovascularization variability in mice.
AB  - BACKGROUND: Retinal argon laser coagulation is an established procedure for
      induction of choroidal neovascularization (CNV) in rodents. This study aimed to
      evaluate the in-vivo and ex-vivo morphology and variability of laser-induced CNV
      spots over time. METHODS: Female C57/Bl/6 mice, 3-6 months of age, were treated
      with five spots of retinal argon laser coagulation per eye (150 mW, 100 ms, 50
      MUm). In-vivo fluorescein angiography (FA) and standard high-resolution spectral
      domain optical coherence tomography (SD-OCT) were performed on day (d) 0, d1, d4,
      d7, d14 and d21. Ex-vivo histology, CD31 immunostaining, flatmount and confocal
      microscopy were also conducted. CNV size in the retinal and choroidal focus, CNV
      morphology, central retinal thickness (CRT) and FA CNV activity grading were
      assessed in-vivo at all times and compared to the ex-vivo assessments. RESULTS:
      SD-OCT revealed sub-retinal and intra-retinal fluid, and permitted evaluation of
      longitudinal morphologic changes of the induced CNV. Laser spot area in FA and
      CRT in SD-OCT did not differ in longitudinal evaluation. CNV could not be
      consistently outlined on SD-OCT images, and CNV volume as assessed on SD-OCT did
      not change over time. Significant CNV activity changes were only found in FA CNV
      activity grading, peaking on d4 and decreasing by d7. CONCLUSIONS: Non-invasive
      SD-OCT provides additional morphological information on laser-induced CNV.
      However, reliable evaluation of CNV requires FA. Spontaneous regression of CNV
      activity within 14 days after induction has to be taken into account when
      utilizing this model for testing the efficacies of potential future treatments.

PMID- 22419038
TI  - 5-Substituted dipyrranes: synthesis and reactivity.
AB  - Dipyrranes constitute important building blocks in the synthesis of porphyrins,
      corroles, chlorins, calix[4]pyrroles, porphodimethenes, BODIPY dyes and
      dipyrrinato complexes. This tutorial review describes the overall progress made
      in the last twenty years in this field, mainly focusing on the most practical and
      useful synthetic methodologies and offers a critical comparison of various
      conditions reported in the literature. This review also deals with the reactivity
      of 5-substituted dipyrranes presenting the scope of their reactions with
      electrophiles.

PMID- 22419037
TI  - Cav 1.3 L-type Ca ( 2+) channels mediate long-term adaptation in dopamine D2L
      mediated GluA1 trafficking in the dorsal striatum following cocaine exposure.
AB  - AMPA receptor (AMPAR) plasticity at glutamatergic synapses in the mesostriatal
      dopaminergic pathway has been implicated in persistent cocaine-induced behavioral
      responses; however, the precise mechanism underlying these changes remains
      unknown. Utilizing cocaine psychomotor sensitization in mice we find that
      repeated cocaine results in a basal reduction of Ser 845 GluA1 and cell surface
      GluA1 levels in the dorsal striatum (dStr) following a protracted withdrawal
      period, an adaptation that is dependent on Cav 1.3 channels but not those
      expressed in the VTA. We find that the basally-induced decrease in this
      phosphoprotein is the result of recruitment of the striatal dopamine D2 pathway,
      as evidenced by enhanced levels of D2 receptor (D2R) mRNA expression and D2R
      function as examined using the D2R antagonist, eticlopride, as well as
      alterations in the phosphorylation status of several downstream molecular targets
      of D2R's, including CREB, DARPP-32, Akt and GSK3beta. Taken together with our
      recently published findings examining similar phenomena in the nucleus accumbens
      (NAc), these results underscore the utilization of divergent molecular mechanisms
      in the dStr, in mediating cocaine-induced persistent behavioral changes.

PMID- 22419041
TI  - KLOTHO methylation is linked to uremic toxins and chronic kidney disease.
AB  - Epigenetic regulation plays a major role in uremic toxin-induced chronic kidney
      disease (CKD) progression. The KLOTHO protein is a key modulator of homeostasis
      in renal function. Uremic toxin accumulation can induce DNA methyltransferase
      (DNMT) protein expression, which is involved in the silencing of KLOTHO through
      hypermethylation. Treatment with DNMT inhibitors can induce a hypermethylated
      status of KLOTHO and suppress mRNA and protein expression. Epigenetic targeting
      of specific genes may become an effective strategy to prevent progression of
      uremia-related CKD.

PMID- 22419042
TI  - Renal BOLD-MRI and assessment for renal hypoxia.
AB  - Renal tissue hypoxia may play a major role in the progression of chronic renal
      disease. Michaely et al. used blood oxygen level-dependent magnetic resonance
      imaging to test this hypothesis. They found no relationship between renal
      oxygenation and stage of chronic kidney disease (CKD). However, renal tissue
      oxygenation may be related not only to the severity of renal disease but also to
      its underlying etiology. This added complexity confounds interpretation of data
      obtained from subjects with CKD due to multiple etiologies.

PMID- 22419043
TI  - Viper venom for diabetic nephropathy.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease in the
      United States. Renin-angiotensin-aldosterone system (RAAS) blockers are thought
      to have a specific renoprotective effect in diabetes. Hirst et al. report the
      results of randomized clinical trials assessing the effects of RAAS inhibitors on
      urinary albumin excretion levels in diabetic patients. Although reductions in
      urinary albumin excretion were observed, whether RAAS inhibitors offer additional
      protection over other antihypertensive agents is unclear.

PMID- 22419044
TI  - A progression in peritubular capillary flow reduction and tubulointerstitial
      fibrosis reflected by FE Mg predict the decline in glomerular filtration rate.

PMID- 22419047
TI  - Renal hemosiderosis complicating sickle cell anemia.

PMID- 22419048
TI  - The case ? a 62-year-old man with severe alkalosis.

PMID- 22419049
TI  - Reducing bloodstream infections in an outpatient hemodialysis center--New Jersey,
      2008-2011.
AB  - Patients undergoing hemodialysis are at risk for bloodstream infections (BSIs),
      and preventing these infections in this high-risk population is a national
      priority. During 2008, an estimated 37,000 BSIs related to central lines occurred
      among hemodialysis patients in the United States. This is almost as many as the
      estimated 41,000 central line-associated BSIs that occurred during 2009 among
      patients in critical-care units and wards of acute-care hospitals. In 2009, to
      decrease BSI incidence in a New Jersey outpatient hemodialysis center, a package
      of interventions was instituted, beginning with participation in a national
      collaborative BSI prevention program and augmented by a social and behavioral
      change process to enlist staff members in infection prevention. Rates of BSIs
      related to the patient's vascular access (i.e., access-related BSIs [ARBs]) were
      evaluated in the preintervention and postintervention periods. The incidence of
      all ARBs decreased from 2.04 per 100 patient-months preintervention to 0.75
      (p=0.03) after initiating program interventions and to 0.24 (p<0.01) after adding
      a behavioral change intervention. Only one ARB occurred during the last 12
      postintervention months. At this hemodialysis facility, participating in a
      collaborative prevention program along with implementation of a behavioral change
      strategy was associated with a large decrease in ARBs. Other outpatient
      hemodialysis facilities also might reduce ARBs by adopting similar approaches to
      prevention.

PMID- 22419050
TI  - Tickborne relapsing fever in a mother and newborn child--Colorado, 2011.
AB  - Tickborne relapsing fever (TBRF) is a bacterial infection caused by certain
      species of Borrelia spirochetes and transmitted through the bite of Ornithodoros
      ticks. Clinical illness is characterized by relapsing fever, myalgias, and
      malaise. On May 10, 2011, CDC and the Colorado Department of Public Health and
      Environment were notified of two patients with TBRF: a young woman and her
      newborn child. This report summarizes the clinical course of these patients and
      emphasizes the importance of considering a diagnosis of TBRF among patients with
      compatible clinical symptoms and residence or travel in a TBRF-endemic area.
      Pregnant women and neonates are at increased risk for TBRF-associated
      complications and require prompt diagnosis and treatment for optimal clinical
      outcomes. Public health follow-up of reported TBRF cases should include a search
      for persons sharing an exposure with the patient and environmental investigation
      with remediation measures to prevent additional infections.

PMID- 22419051
TI  - Pre- and postoperative imaging of adolescents undergoing laparoscopic adjustable
      gastric banding surgery.
AB  - BACKGROUND: As childhood obesity rates rise, laparoscopic adjustable gastric
      banding (LAGB) is being investigated as a bariatric surgical option in
      adolescents. OBJECTIVE: To examine pre- and postoperative imaging in adolescents
      undergoing LAGB, describe the most common abnormal preoperative imaging findings,
      and illustrate the typical appearance and variants on postoperative upper
      gastrointestinal (UGI) examinations. MATERIALS AND METHODS: A retrospective chart
      review was performed of all adolescents from 2008 to 2010 undergoing LAGB at a
      single tertiary-care pediatric hospital. The picture archiving and communication
      system was queried for all imaging obtained before and after surgery.
      Postoperative UGI studies were analyzed for common patterns. RESULTS: Twenty
      seven obese adolescents who underwent LAGB were identified. Twenty-five had
      preoperative imaging, most commonly a UGI study (81.5%). Eight UGI studies were
      abnormal but did not impact surgery. Preoperative chest and neck radiographs were
      also common. Intraoperative imaging was rare. Seventy-three postoperative UGI
      studies were performed on 22 children (range, 2-12 studies). A common
      postoperative imaging pattern was observed in 19/22 (86%) children. No
      complications were observed. CONCLUSION: The most common pre- and postoperative
      imaging studies in adolescents undergoing LAGB are UGI studies. Pediatric
      radiologists should be familiar with the imaging of LAGB as this procedure
      becomes increasingly common.

PMID- 22419052
TI  - Hepatoblastoma imaging with gadoxetate disodium-enhanced MRI--typical, atypical,
      pre- and post-treatment evaluation.
AB  - Gadoxetate disodium (Gd-EOB-DTPA) is a hepatobiliary MRI contrast agent widely
      used in adults for characterization of liver tumors and increasingly used in
      children. Hepatoblastoma is the most common primary hepatic malignancy of
      childhood. In this review, we describe our experience with this agent both before
      and after initiating therapy in children with hepatoblastoma.

PMID- 22419053
TI  - Energetics of ligand binding to the DNA minor groove.
AB  - In the present work the decomposition of the total Gibbs free energy of ligand
      DNA binding onto various physical terms was accomplished for the group of nine
      DNA minor groove binders (MGB ligands) differing in both structure and charge
      state. The decomposition protocol includes the analysis of the most complete set
      of physical factors known to contribute to the complexation process, viz. the net
      change in the number of degrees of freedom (translational, rotational, vibrations
      of the chemical bonds and vibrations of the ligand as a whole within the binding
      site), the conformational entropy, van der Waals, electrostatic and hydrophobic
      interactions, the polyelectrolyte contribution and the net effect of changes in
      the number of hydrogen bonds. All of these processes are further decomposed into
      the interaction with the solvent and the interaction of the ligand with DNA. The
      principal outcome of the decomposition is the possibility of performing a
      comparative analysis of the energetic contribution of various physical terms and
      provide an answer to the question concerning what physical factors stabilize or
      destabilize the complexes of MGB ligands with DNA.

PMID- 22419054
TI  - Lamivudine salts with improved solubilities.
AB  - To optimize solubility of drugs, current strategies mainly focus on engineering
      and screening of smart crystal phases. Two salts of the anti-human
      immunodeficiency virus (HIV) drug lamivudine--namely, lamivudine hydrochloride
      and lamivudine hydrochloride monohydrate, were prepared in the course of
      screening the crystallization conditions of lamivudine duplex, an uncommon DNA
      mimic, double-stranded helical structure made up of partially protonated drug
      pairs. Here, water solubilities of lamivudine hydrochloride, lamivudine
      hydrochloride monohydrate, and lamivudine duplex are reported. The aqueous
      solubility of this anti-HIV drug was significantly increased in both salts and
      also in lamivudine duplex in relation to the water solubility of lamivudine form
      II. In comparison with the lamivudine form II incorporated into therapeutic
      formulations, the drug solubility was increased at a temperature of 299 +/- 2 K
      by factors of 1.2, 3.3, and 4.5 in lamivudine hydrochloride, lamivudine
      hydrochloride monohydrate, and lamivudine duplex, respectively, demonstrating
      that this solid-state property of lamivudine can be improved by crystal
      engineering strategies. Solubility profiles were understood on the basis of
      structural and solvent-solute interaction approaches. At last, correlations
      between solubility and crystal structures allowed for a rational approach to
      understand how this physicochemical feature could be enhanced by engineering new
      salts of the drug.

PMID- 22419055
TI  - (1)H, (13)C and (15)N NMR assignment of CGC-19, a single domain proteic
      constituent of a non ribosomal peptide synthetase.
AB  - CGC-19, a 14 kDa proteic constituent of a non ribosomal peptide synthetase
      implicated in the biosynthesis of a secondary metabolite in Streptomyces
      ambofaciens, has been isotopically enriched and recombinantly expressed. Its
      nearly complete (1)H, (13)C and (15)N resonance assignment is reported hereunder.

PMID- 22419056
TI  - Intrarectal nitric oxide administration prevents cellular infiltration but not
      colonic injury during dextran sodium sulfate colitis.
AB  - BACKGROUND: During inflammation in the gastrointestinal tract, the production of
      nitric oxide (NO) is mediated by the mucosal conversion of L-arginine. Recently,
      it was shown that the gut microbiota can also produce NO. AIMS: The effect of gut
      luminal NO on inflammatory processes of an experimental colitis mice model was
      investigated by administrating NO directly to the colon, mimicking microbial NO
      production. METHODS: Twenty-four mice received daily intrarectal treatment with a
      NO donor in 2 doses and 8 mice were treated with placebo. Starting 1 day later,
      18 of these mice were fed ad libitum with 4% of dextran sodium sulfate (DSS) in
      their drinking water to induce colitis. At day 6, histopathology (both the
      inflammation and damage score), myeloperoxidase (MPO)-activity, colon length and
      colonic permeability were evaluated. RESULTS: Co-administration of NO during DSS
      exposure inhibited the induction of an increasing colonic MPO-activity. This
      protective effect of NO was confirmed by the histological inflammation score
      showing a similar trend. The colonic permeability was restored when very low
      levels of NO were administered to the DSS-mice. On the other hand, the colon
      length of the NO-treated DSS-mice was negatively correlated with the NO dose and
      the histological damage score was not improved. CONCLUSIONS: Our results indicate
      that intrarectal administration of NO has clear anti-inflammatory effects in
      experimental colitis, but does not prevent colonic damage. Therefore, NO
      producing microorganisms in the gut lumen should be accounted as a modulating
      process during colitis.

PMID- 22419057
TI  - Lipid-lowering agents in nonalcoholic fatty liver disease and steatohepatitis:
      human studies.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease which refers
      to the presence of hepatic steatosis without significant intake of alcohol. NAFLD
      is an asymptomatic disease that can progress to nonalcoholic steatohepatitis
      (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD is currently the
      most common cause of incidental abnormal liver tests and elevated serum liver
      enzyme activities in the developed world. Obesity, diabetes, and other components
      of the metabolic syndrome are frequently associated with the NAFLD. The treatment
      of NAFLD focuses on life-style modifications. Statins, fibrates, and other lipid
      lowering agents have been proposed as effective lipid-lowering treatments in
      patients with NAFLD/NASH. However, clinicians are concerned that hyperlipidemic
      patients with NAFLD/NASH who are treated with statins could develop
      transaminitis. We assessed the efficacy and safety of lipid-lowering agents for
      NAFLD/NASH by reviewing reports of human studies including pilot, prospective,
      preliminary, and post hoc analysis studies on online databases during the period
      of 1980 to December 2012. The results of studies provide compelling evidence that
      lipid-lowering agents are safe and efficacious in patients with NAFLD/NASH and
      that some of these agents can induce a reduction in the extent of the hepatic
      steatosis. Well-designed randomized controlled studies of adequate size and
      duration with histological endpoints are needed in order to establish a suitable
      lipid-lowering treatment for hyperlipidemic patients with NAFLD/NASH, and for
      nonhyperlipidemic patients with NAFLD/NASH with a high risk for cardiovascular
      disease.

PMID- 22419058
TI  - Stone foreign body--radiographic and CT appearance.
AB  - Mineral foreign bodies (stones) are infrequent findings in clinical and
      radiological practice. However, a growing number of reports indicate that they
      raise clinical and diagnostic concern in ophthalmology, neurosurgery,
      maxillofacial surgery, otolaryngology, gastroenterology, and vascular surgery.
      Dense finding in the soft tissue without clear history of foreign body
      penetration may represent diagnostic challenge mimicking calcifications or bony
      fragments. The aim of this work is to analyze the appearance of stone foreign
      bodies on radiographs and computed tomography. A collection of minerals and rocks
      was used for analysis. The clinical case of a stony foreign body which penetrated
      into the soft tissue of the leg is used to demonstrate the diagnostic challenge
      and management. Available literature describing imaging characteristics of stones
      was reviewed. The results of this work will help in diagnostic interpretation and
      assessment of stone foreign body composition.

PMID- 22419059
TI  - Ectopic expression of TrKA in the adult rat basal ganglia induces both nerve
      growth factor-dependent and -independent neuronal responses.
AB  - Ectopic expression of tropomyosin-related kinase A (TrkA), the high-affinity
      receptor of nerve growth factor (NGF), has been widely used in cell culture
      systems to uncover its role in cell survival or death events. In contrast, little
      is known about the consequences of its expression in vivo. To address this
      question, adeno-associated virus (AAV) vectors were used to express TrkA in the
      substantia nigra (SN) and striatum of adult rats. Nine weeks after transfer,
      tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNAs were slightly
      decreased in the ipsilateral SN. This decrease was no longer significant when NGF
      was delivered into the striatum. There was no change of DAT binding sites or D1
      or D2 receptor mRNAs and binding sites in the striatum, suggesting that ectopic
      TrkA exerts a limited effect on the pool of TH and DAT transcripts, without
      affecting overall dopamine signaling. When transferred into the striatum, TrkA
      transgene had no effect on the size of the cholinergic interneurons, but it
      exerted typical neurotrophic effects, as shown by an enlargement of the
      projection neurons and nitric oxide synthase (nNOS)-expressing interneurons. This
      trophic action was amplified by a delivery of NGF. No toxic effect of the
      transgene was noted. These data indicate that ectopic expression of TrkA may
      result in the promotion of neurotrophic effects or can influence neuronal
      plasticity in the absence of exogenous NGF in neuronal populations that naturally
      fail to respond to this factor.

PMID- 22419060
TI  - Highly enantioselective [4 + 2] cycloadditions of allenoates and dual activated
      olefins catalyzed by N-acyl aminophosphines.
AB  - An asymmetric organocatalytic [4 + 2] cycloaddition between alpha-substituted
      allenoates and dual activated olefins using bifunctional N-acyl aminophosphine
      catalysts is described. The use of 2-cyano acrylate derived olefins led to the
      first successful incorporation of an electrophile derived from an aliphatic
      aldehyde into this reaction.

PMID- 22419061
TI  - Symmetric Epistasis Estimation (SEE) and its application to dissecting
      interaction map of Plasmodium falciparum.
AB  - It is being increasingly recognized that many important phenotypic traits,
      including various diseases, are governed by a combination of weak genetic effects
      and their interactions. While the detection of epistatic interactions that
      involve a non-additive effect of two loci on a quantitative trait is particularly
      challenging, this interaction type is fundamental for the understanding of genome
      organization and gene regulation. However, current methods that detect epistatic
      interactions typically rely on the existence of a strong primary effect,
      considerably limiting the sensitivity of the search. To fill this gap, we
      developed a new method, SEE (Symmetric Epistasis Estimation), allowing the genome
      wide detection of epistatic interactions without the need for a strong primary
      effect. We applied our approach to progeny crosses of the human malaria parasite
      P. falciparum and S. cerevisiae. We found an abundance of epistatic interactions
      in the parasite and a much smaller number of such interactions in yeast. The
      genome of P. falciparum also harboured several epistatic interaction hotspots
      that putatively play a role in drug resistance mechanisms. The abundance of
      observed epistatic interactions might suggest a mechanism of compensation for the
      extremely limited repertoire of transcription factors. Interestingly, epistatic
      interaction hotspots were associated with elevated levels of linkage
      disequilibrium, an observation that suggests selection pressure acting on P.
      falciparum, potentially reflecting host-pathogen interactions or drug-induced
      selection.

PMID- 22419062
TI  - An effective intra-operative neurophysiological monitoring scheme for aneurysm
      clipping and spinal fusion surgeries.
AB  - Somatosensory-evoked potentials (SSEPs) have been widely used for intra-operative
      neurophysiological monitoring (IONM). Currently at least 200-300 trials are
      required to generate a readable SSEP signal. This study introduces a novel
      approach that yields accurate detection results of the SSEP signal yet with a
      significantly reduced number of trials, resulting in an effectual monitoring
      process. The analysis was performed on data recorded in seven patients undergoing
      surgery, where the posterior tibial nerve was stimulated and the SSEP response
      was recorded from scalp electroencephalography using two bipolar electrodes, C(3)
      C(4) and C(Z)-F(Z). The proposed approach employs an innovative, simple yet
      effective algorithm based on a patient-specific Gaussian template to detect the
      SSEP using only 30 trials. The time latencies of the P37 and N45 peaks are
      detected along with the peak-to-peak amplitudes. The time latencies are detected
      with a mean accuracy greater than 95%. Also, the P37 and N45 peak latencies and
      the peak-to-peak amplitude were found to be consistent throughout the surgical
      procedure within the 10% and 50% acceptable clinical limits, respectively. The
      results obtained support the assertion that the algorithm is capable of detecting
      SSEPs with high accuracy and consistency throughout the entire surgical procedure
      using only 30 trials.

PMID- 22419064
TI  - DNA methylation in neonates born to women receiving psychiatric care.
AB  - Prenatal exposure both to maternal psychiatric illness and psychiatric medication
      has been linked with adverse child outcomes that affect physiological, emotional
      and psychiatric development. Studies suggest that epigenetic mechanisms, such as
      DNA methylation, may facilitate these effects. In this report, we explore the
      association between maternal psychiatric illness and treatment during pregnancy
      and neonatal DNA methylation patterns in a prospectively-characterized clinical
      cohort of 201 dyads. Associations between the percent of umbilical cord blood DNA
      methylated at 27,578 CpG sites and maternal psychiatric diagnosis, symptoms and
      antidepressant use were evaluated by fitting a separate linear mixed effects
      model for each CpG site. There were no significant changes in neonatal DNA
      methylation attributable to maternal psychiatric diagnosis or depressive symptoms
      during pregnancy. Exposure to an antidepressant medication was associated with
      differential methylation of CpG sites in TNFRSF21 and CHRNA2 (false discovery
      rate < 0.05), but the average difference in methylation for both CpG sites was
      less than 3% between each group. The results were not specific to type of
      antidepressant or duration of the exposure. This study suggests that there are no
      large effects of maternal psychiatric illness, depressive symptoms or prenatal
      exposure to antidepressants on neonatal DNA methylation. Delineation of the
      influence of maternal psychiatric illness and pharmacological exposures on the
      developing fetuses has critical implications for clinical care during pregnancy.

PMID- 22419065
TI  - Mitochondrial regulation of epigenetics and its role in human diseases.
AB  - Most pathogenic mitochondrial DNA (mtDNA) mutations induce defects in
      mitochondrial oxidative phosphorylation (OXPHOS). However, phenotypic effects of
      these mutations show a large degree of variation depending on the tissue
      affected. These differences are difficult to reconcile with OXPHOS as the sole
      pathogenic factor suggesting that additional mechanisms contribute to lack of
      genotype and clinical phenotype correlationship. An increasing number of studies
      have identified a possible effect on the epigenetic landscape of the nuclear
      genome as a consequence of mitochondrial dysfunction. In particular, these
      studies demonstrate reversible or irreversible changes in genomic DNA methylation
      profiles of the nuclear genome. Here we review how mitochondria damage checkpoint
      (mitocheckpoint) induces epigenetic changes in the nucleus. Persistent pathogenic
      mutations in mtDNA may also lead to epigenetic changes causing genomic
      instability in the nuclear genome. We propose that "mitocheckpoint" mediated
      epigenetic and genetic changes may play key roles in phenotypic variation related
      to mitochondrial diseases or host of human diseases in which mitochondrial defect
      plays a primary role.

PMID- 22419066
TI  - Selective DNA demethylation by fusion of TDG with a sequence-specific DNA-binding
      domain.
AB  - Our ability to selectively manipulate gene expression by epigenetic means is
      limited, as there is no approach for targeted reactivation of epigenetically
      silenced genes, in contrast to what is available for selective gene silencing. We
      aimed to develop a tool for selective transcriptional activation by DNA
      demethylation. Here we present evidence that direct targeting of thymine-DNA
      glycosylase (TDG) to specific sequences in the DNA can result in local DNA
      demethylation at potential regulatory sequences and lead to enhanced gene
      induction. When TDG was fused to a well-characterized DNA-binding domain [the Rel
      homology domain (RHD) of NFkappaB], we observed decreased DNA methylation and
      increased transcriptional response to unrelated stimulus of inducible nitric
      oxide synthase (NOS2). The effect was not seen for control genes lacking either
      RHD-binding sites or high levels of methylation, nor in control mock-transduced
      cells. Specific reactivation of epigenetically silenced genes may thus be
      achievable by this approach, which provides a broadly useful strategy to further
      our exploration of biological mechanisms and to improve control over the
      epigenome.

PMID- 22419067
TI  - Epigenetic reprogramming of cancer cells via targeted DNA methylation.
AB  - An obstacle in the treatment of human diseases such as cancer is the inability to
      selectively and effectively target historically undruggable targets such as
      transcription factors. Here, we employ a novel technology using artificial
      transcription factors (ATFs) to epigenetically target gene expression in cancer
      cells. We show that site-specific DNA methylation and long-term stable repression
      of the tumor suppressor Maspin and the oncogene SOX2 can be achieved in breast
      cancer cells via zinc-finger ATFs targeting DNA methyltransferase 3a (DNMT3a) to
      the promoters of these genes. Using this approach, we show Maspin and SOX2
      downregulation is more significant as compared with transient knockdown, which is
      also accompanied by stable phenotypic reprogramming of the cancer cell. These
      findings indicate that multimodular Zinc Finger Proteins linked to epigenetic
      editing domains can be used as novel cell resources to selectively and heritably
      alter gene expression patterns to stably reprogram cell fate.

PMID- 22419068
TI  - Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5
      methylation.
AB  - Smyd3 is a lysine methyltransferase implicated in chromatin and cancer
      regulation. Here we show that Smyd3 catalyzes histone H4 methylation at lysine 5
      (H4K5me). This novel histone methylation mark is detected in diverse cell types
      and its formation is attenuated by depletion of Smyd3 protein. Further, Smyd3
      driven cancer cell phenotypes require its enzymatic activity. Thus, Smyd3, via
      H4K5 methylation, provides a potential new link between chromatin dynamics and
      neoplastic disease.

PMID- 22419069
TI  - Genome-wide DNA methylation studies suggest distinct DNA methylation patterns in
      pediatric embryonal and alveolar rhabdomyosarcomas.
AB  - Rhabdomyosarcoma is the most common soft-tissue sarcoma in children. While
      cytogenetic abnormalities have been well characterized in this disease, aberrant
      epigenetic events such as DNA hypermethylation have not been described in genome
      wide studies. We have analyzed the methylation status of 25,500 promoters in
      normal skeletal muscle, and in cell lines and tumor samples of embryonal and
      alveolar rhabdomyosarcoma from pediatric patients. We identified over 1,900 CpG
      islands that are hypermethylated in rhabdomyosarcomas relative to skeletal
      muscle. Genes involved in tissue development, differentiation, and oncogenesis
      such as DNAJA4, HES5, IRX1, BMP8A, GATA4, GATA6, ALX3, and P4HTM were
      hypermethylated in both RMS cell lines and primary samples, implicating aberrant
      DNA methylation in the pathogenesis of rhabdomyosarcoma. Furthermore, cluster
      analysis revealed embryonal and alveolar subtypes had distinct DNA methylation
      patterns, with the alveolar subtype being enriched in DNA hypermethylation of
      polycomb target genes. These results suggest that DNA methylation signatures may
      aid in the diagnosis and risk stratification of pediatric rhabdomyosarcoma and
      help identify new targets for therapy.

PMID- 22419070
TI  - A simple method for high-throughput quantification of genome-wide DNA methylation
      by fluorescence polarization.
AB  - To rapidly determine DNA methylation levels from a large number of biological or
      clinical samples, we have developed an accurate and sensitive method for high
      throughput quantification of global methylation of 5'-Cm ( 5) CGG-3' sites in the
      genome, visualized by fluorescence polarization (FP) based measurement of DNA
      methylation (FPDM). In FPDM, the methyl-sensitive HpaII and methyl-insensitive
      MspI restriction enzymes were employed to achieve DNA cleavage, followed by
      incorporation of fluorescent dCMP into the enzyme-cleavage products through
      polymerase chain extension, yielding an FP-ratio between the HpaII- and MspI
      restricted preparations as a measure of methylation. FPDM provided stable
      estimates of methylation level of submicrograms of lambda or human DNA, and of a
      255-bp DNA segment containing a single HpaII/MspI restriction site in accord
      with, and more accurate than, determination by gel electrophoresis. FPDM was also
      applied to measure dose-dependent DNA hypomethylation in human embryonic kidney
      293T cells treated with the DNA-methyltransferase inhibitor 5-aza-dC.

PMID- 22419071
TI  - 5-hydroxymethyl-cytosine enrichment of non-committed cells is not a universal
      feature of vertebrate development.
AB  - 5-hydroxymethyl-cytosine (5-hmC) is a cytosine modification that is relatively
      abundant in mammalian pre-implantation embryos and embryonic stem cells (ESC)
      derived from mammalian blastocysts. Recent observations imply that both 5-hmC and
      Tet1/2/3 proteins, catalyzing the conversion of 5-methyl-cytosine to 5-hmC, may
      play an important role in self renewal and differentiation of ESCs. Here we
      assessed the distribution of 5-hmC in zebrafish and chick embryos and found that,
      unlike in mammals, 5-hmC is immunochemically undetectable in these systems before
      the onset of organogenesis. In addition, Tet1/2/3 transcripts are either low or
      undetectable at corresponding stages of zebrafish development. However, 5-hmC is
      enriched in later zebrafish and chick embryos and exhibits tissue-specific
      distribution in adult zebrafish. Our findings show that 5-hmC enrichment of non
      committed cells is not a universal feature of vertebrate development and give
      insights both into evolution of embryonic pluripotency and the potential role of
      5-hmC in its regulation.

PMID- 22419073
TI  - Linear-scaling quantum mechanical methods for excited states.
AB  - The poor scaling of many existing quantum mechanical methods with respect to the
      system size hinders their applications to large systems. In this tutorial review,
      we focus on latest research on linear-scaling or O(N) quantum mechanical methods
      for excited states. Based on the locality of quantum mechanical systems, O(N)
      quantum mechanical methods for excited states are comprised of two categories,
      the time-domain and frequency-domain methods. The former solves the dynamics of
      the electronic systems in real time while the latter involves direct evaluation
      of electronic response in the frequency-domain. The localized density matrix
      (LDM) method is the first and most mature linear-scaling quantum mechanical
      method for excited states. It has been implemented in time- and frequency
      domains. The O(N) time-domain methods also include the approach that solves the
      time-dependent Kohn-Sham (TDKS) equation using the non-orthogonal localized
      molecular orbitals (NOLMOs). Besides the frequency-domain LDM method, other O(N)
      frequency-domain methods have been proposed and implemented at the first
      principles level. Except one-dimensional or quasi-one-dimensional systems, the
      O(N) frequency-domain methods are often not applicable to resonant responses
      because of the convergence problem. For linear response, the most efficient O(N)
      first-principles method is found to be the LDM method with Chebyshev expansion
      for time integration. For off-resonant response (including nonlinear properties)
      at a specific frequency, the frequency-domain methods with iterative solvers are
      quite efficient and thus practical. For nonlinear response, both on-resonance and
      off-resonance, the time-domain methods can be used, however, as the time-domain
      first-principles methods are quite expensive, time-domain O(N) semi-empirical
      methods are often the practical choice. Compared to the O(N) frequency-domain
      methods, the O(N) time-domain methods for excited states are much more mature and
      numerically stable, and have been applied widely to investigate the dynamics of
      complex molecular systems.

PMID- 22419072
TI  - CD1d induction in solid tumor cells by histone deacetylase inhibitors through
      inhibition of HDAC1/2 and activation of Sp1.
AB  - CD1d is a MHC class-like molecule that presents glycolipids to natural killer T
      (NKT) cells, then regulates innate and adaptive immunity. The regulation of CD1d
      gene expression in solid tumors is still largely unknown. Gene expression can be
      epigenetically regulated by DNA methylation and histone acetylation. We found
      that histone deacetylase inhibitors, trichostatin A (TSA) and suberoylanilide
      hydroxamic acid (SAHA), induced CD1d gene expression in human (A549 and NCI-H292)
      and mouse (TC-1 and B16/F0) cancer cells. Simultaneous knockdown of HDAC1 and 2
      induced CD1d gene expression. Sp1 inhibitor mitramycin A (MTM) blocked TSA- and
      SAHA-induced CD1d mRNA expression and Sp1 luciferase activity. Co-transfection of
      GAL4-Sp1 and Fc-luciferase reporters demonstrated that TSA and SAHA induced Sp1
      luciferase reporter activity by enhancing Sp1 transactivation activity. The
      binding of Sp1 to CD1d promoter and histone H3 acetylation on Sp1 sites were
      increased by TSA and SAHA. These results indicate that TSA and SAHA could up
      regulate CD1d expression in tumor cells through inhibition of HDAC1/2 and
      activation of Sp1.

PMID- 22419074
TI  - Excited state dynamics and catalytic mechanism of the light-driven enzyme
      protochlorophyllide oxidoreductase.
AB  - The reduction of protochlorophyllide (Pchlide) to chlorophyllide, catalysed by
      the enzyme protochlorophyllide oxidoreductase (POR), is the penultimate step in
      the chlorophyll biosynthetic pathway and is a key light-driven reaction that
      triggers a profound transformation in plant development. As POR is light
      activated it can provide new information on the way in which light energy can be
      harnessed to power enzyme reactions. Consequently, POR presents a unique
      opportunity to study catalysis at low temperatures and on ultrafast timescales,
      which are not usually accessible for the majority of enzymes. Recent advances in
      our understanding of the catalytic mechanism of POR illustrate why it is an
      important model for studying enzyme catalysis and reaction dynamics. The reaction
      involves the addition of one hydride and one proton, and catalysis is initiated
      by the absorption of light by the Pchlide substrate. As the reaction involves the
      Pchlide excited state, a variety of ultrafast spectroscopic measurements have
      shown that significant parts of the reaction occur on the picosecond timescale. A
      number of excited state Pchlide species, including an intramolecular charge
      transfer complex and a hydrogen bonded intermediate, are proposed to be required
      for the subsequent hydride and proton transfers, which occur on the microsecond
      timescale. Herein, we review spectroscopic investigations, with a particular
      focus on time-resolved transient absorption and fluorescence experiments that
      have been used to study the excited state dynamics and catalytic mechanism of
      POR.

PMID- 22419075
TI  - Fine-structural distribution of MMP-2 and MMP-9 activities in the rat skeletal
      muscle upon training: a study by high-resolution in situ zymography.
AB  - Matrix metalloproteinases (MMPs) are key regulators of extracellular matrix
      remodeling, but have also important intracellular targets. The purpose of this
      study was to examine the activity and subcellular localization of the gelatinases
      MMP-2 and MMP-9 in skeletal muscle of control and physically trained rats. In
      control hind limb muscle, the activity of the gelatinases was barely detectable.
      In contrast, after 5 days of intense exercise, in Soleus (Sol), but not Extensor
      digitorum longus (EDL) muscle, significant upregulation of gelatinolytic activity
      in myofibers was observed mainly in the nuclei, as assessed by high resolution in
      situ zymography. The nuclei of quiescent satellite cells did not contain the
      activity. Within the myonuclei, the gelatinolytic activity colocalized with an
      activated RNA Polymerase II. Also in Sol, but not in EDL, there were few foci of
      mononuclear cells with strongly positive cytoplasm, associated with apparent
      necrotic myofibers. These cells were identified as activated satellite
      cells/myoblasts. No extracellular gelatinase activity was observed. Gel
      zymography combined with subcellular fractionation revealed training-related
      upregulation of active MMP-2 in the nuclear fraction, and increase of active MMP
      9 in the cytoplasmic fraction of Sol. Using RT-PCR, selective increase in MMP-9
      mRNA was observed. We conclude that training activates nuclear MMP-2, and
      increases expression and activity of cytoplasmic MMP-9 in Sol, but not in EDL.
      Our results suggest that the gelatinases are involved in muscle adaptation to
      training, and that MMP-2 may play a novel role in myonuclear functions.

PMID- 22419076
TI  - Amber mutants of bacteriophage T4D: their isolation and genetic characterization.
AB  - We have isolated a large number of mutants of bacteriophage T4D that are unable
      to form plaques on strain B of Escherichia coli, but are able to grow (nearly)
      normally on some other strains of E. coli, in particular strain CR63. These
      mutants, designated amber (am), have been characterized by complementation tests,
      by genetic crosses, and by their response to chemical mutagens. It is concluded
      that a particular subclass of base substitution mutations may give rise to amber
      mutants and that such mutants occur in many genes, which are widely distributed
      over the T4 genome.

PMID- 22419077
TI  - Gene overexpression: uses, mechanisms, and interpretation.
AB  - The classical genetic approach for exploring biological pathways typically begins
      by identifying mutations that cause a phenotype of interest. Overexpression or
      misexpression of a wild-type gene product, however, can also cause mutant
      phenotypes, providing geneticists with an alternative yet powerful tool to
      identify pathway components that might remain undetected using traditional loss
      of-function analysis. This review describes the history of overexpression, the
      mechanisms that are responsible for overexpression phenotypes, tests that begin
      to distinguish between those mechanisms, the varied ways in which overexpression
      is used, the methods and reagents available in several organisms, and the
      relevance of overexpression to human disease.

PMID- 22419082
TI  - Igf1 expression in mouse model of liver carcinogenesis.

PMID- 22419083
TI  - H-atom tunneling in biological reactions.

PMID- 22419084
TI  - Molecular analysis of enhancer RNAs and chromatin modifications in the region of
      their synthesis in Drosophila cells possessing genetic constructs.

PMID- 22419085
TI  - Magnetic-isotope effect of magnesium in the living cell.

PMID- 22419086
TI  - The influence of leaf senescence on light dependence of chlorophyll fluorescence
      of radish leaves.

PMID- 22419078
TI  - The yeast nuclear pore complex and transport through it.
AB  - Exchange of macromolecules between the nucleus and cytoplasm is a key regulatory
      event in the expression of a cell's genome. This exchange requires a dedicated
      transport system: (1) nuclear pore complexes (NPCs), embedded in the nuclear
      envelope and composed of proteins termed nucleoporins (or "Nups"), and (2)
      nuclear transport factors that recognize the cargoes to be transported and ferry
      them across the NPCs. This transport is regulated at multiple levels, and the NPC
      itself also plays a key regulatory role in gene expression by influencing nuclear
      architecture and acting as a point of control for various nuclear processes. Here
      we summarize how the yeast Saccharomyces has been used extensively as a model
      system to understand the fundamental and highly conserved features of this
      transport system, revealing the structure and function of the NPC; the NPC's role
      in the regulation of gene expression; and the interactions of transport factors
      with their cargoes, regulatory factors, and specific nucleoporins.

PMID- 22419087
TI  - Human APP gene expression in nerve cells of Drosophila melanogaster causes
      alteration of synaptoptagmin 1 mRNA level.

PMID- 22419088
TI  - Caffeine modifies effects of X-ray action on mice after exposure to radiation and
      exhibits radioprotective properties.

PMID- 22419079
TI  - Regulation of amino acid, nucleotide, and phosphate metabolism in Saccharomyces
      cerevisiae.
AB  - Ever since the beginning of biochemical analysis, yeast has been a pioneering
      model for studying the regulation of eukaryotic metabolism. During the last three
      decades, the combination of powerful yeast genetics and genome-wide approaches
      has led to a more integrated view of metabolic regulation. Multiple layers of
      regulation, from suprapathway control to individual gene responses, have been
      discovered. Constitutive and dedicated systems that are critical in sensing of
      the intra- and extracellular environment have been identified, and there is a
      growing awareness of their involvement in the highly regulated intracellular
      compartmentalization of proteins and metabolites. This review focuses on recent
      developments in the field of amino acid, nucleotide, and phosphate metabolism and
      provides illustrative examples of how yeast cells combine a variety of mechanisms
      to achieve coordinated regulation of multiple metabolic pathways. Importantly,
      common schemes have emerged, which reveal mechanisms conserved among various
      pathways, such as those involved in metabolite sensing and transcriptional
      regulation by noncoding RNAs or by metabolic intermediates. Thanks to the
      remarkable sophistication offered by the yeast experimental system, a picture of
      the intimate connections between the metabolomic and the transcriptome is
      becoming clear.

PMID- 22419089
TI  - Fragment of intron 5.2 of the human RUNX1 gene important for transcription
      activation is neither enhancer nor MAR-element.

PMID- 22419090
TI  - Characterization of a novel M42 aminopeptidase from crenarchaeon Desulfurococcus
      kamchatkensis.

PMID- 22419091
TI  - The new peptide from the Fea's viper Azemiops feae venom interacts with nicotinic
      acetylcholine receptors.

PMID- 22419092
TI  - Structural study of thrombin binding DNA aptamers by the circular dichroism.

PMID- 22419093
TI  - Amino oxidase activity of hepatopancreas preparations from the octopus
      Bathypolypus arcticus.

PMID- 22419094
TI  - The occurrence of gypenoside XVII in suspension cell culture of ginseng Panax
      japonicus var. repens.

PMID- 22419095
TI  - Variations in noncoding sequences of the mitochondrial DNA in sponges from family
      Lubomirskiidae.

PMID- 22419096
TI  - Protein kinase GSK3beta regulates tumor suppressor Pdcd4 expression in lung
      cancer cells.

PMID- 22419097
TI  - From fragments to morphogenesis: NMR spectroscopy of metabolites in the apex of
      the roots of onion.

PMID- 22419098
TI  - Movement protein of hordeivirus interacts in vitro and in vivo with coilin, a
      major structural protein of Cajal bodies.

PMID- 22419099
TI  - HBV reactivation in malignant lymphoma patients treated with rituximab and
      bendamustine.

PMID- 22419100
TI  - A more sensitive platform for the detection of low-abundance BRAF(V600E)
      mutations.
AB  - Identifying low-abundance mutations is important for the therapy and diagnose of
      cancer. Since the potential for tumor heterogeneity, the efficient detection of
      cancer-relevant mutations largely depends on the sensitivity of the methods
      employed. To confirm whether the mutation detection platforms affect the
      perceived prevalence of the BRAF(V600E) and its correlation with
      clinicopathologic features in papillary thyroid carcinomas (PTC), we compared
      Sanger Sequencing (SS), Pyrosequencing (PS), and a newly built allele-specific
      real-time PCR (AS-qPCR) apparatus for the detection of BRAF(V600E) in a Chinese
      cohort of conventional variant PTC. Accurate plasmid standards were built to
      assess the limit of detection of the three platforms. In this research, AS-qPCR
      has been found both the most sensitive and reliable at detecting mutation. The
      mutations detected by AS-qPCR which were not detected by SS or PS due to low
      abundance were confirmed by mutation enrichment platform COLD-PCR followed by SS.
      When analyzed by AS-qPCR, BRAF(V600E) was associated with a more aggressive
      phenotype. Our results indicate that the reported prevalence of the BRAF(V600E)
      mutations in PTC has been underestimated and more sensitive methods such as AS
      qPCR should be applied in clinical settings.

PMID- 22419101
TI  - Synthesis and evaluation of N-(2,3-dihydroxypropyl)-PEIs as efficient vectors for
      nucleic acids.
AB  - Branched polyethylenimine (bPEI, 25 kDa) has been widely used as an efficient
      delivery vector for nucleic acids in vitro. However, its charge-associated
      toxicity has limited its in vivo applications. In an attempt to control its
      toxicity, it was reacted with varying amounts of glycidol (2,3-epoxy-1-propanol)
      to obtain a small series of hydrophilic polymers, 2,3-dihydroxypropyl-grafted
      polyethylenimines (DHP-g-P). The resulting polymers were characterized by (1)H
      NMR and subjected to interaction with negatively charged pDNA, which yielded
      complexes in the size range of ~171-190 nm with a zeta potential of ~+33-39 mV.
      Acid-base titration revealed no effect of substitution on the buffering capacity
      of the modified polymers. Grafting of 2,3-dihydroxypropyl groups on bPEI
      significantly improved the cell viability (i.e. almost non-toxic) as well as the
      DNA release properties of these modified polymers compared to native bPEI.
      Formation of a relatively loose DHP-g-P25/pDNA complex (the best working system
      in terms of transfection efficiency) resulted in the efficient nuclear release of
      pDNA for transcription, a prerequisite for efficient transfection. Subsequently,
      upon evaluation of their ability to transfer nucleic acids in vitro, the DHP-g
      P/pDNA complexes exhibited higher gene transfection efficiency with one of the
      formulations, DHP-g-P25/DNA complex, displaying ~2.7 folds higher GFP expression
      than bPEI and ~2.3-3.5 folds higher than the selected commercial transfection
      reagents used in this study. Further to quantify the extent of GFP positive
      cells, FACS analysis was performed, which revealed DHP-g-P25/DNA mediated gene
      expression in ~51% cells outcompeting bPEI, SuperfectTM, FugeneTM and
      LipofectamineTM. Sequential delivery of GFP-specific siRNA resulted in ~78%
      suppression of the target gene compared to ~49% achieved by FugeneTM. All these
      results demonstrate the potential of these polymers for in vivo gene delivery.

PMID- 22419102
TI  - The scent of Mare Nostrum: medicinal and aromatic plants in Mediterranean soils.
AB  - In the Mediterranean area, the simultaneous occurrence of pedological, climatic
      and economic constraints often sets a limit on the profitability of agriculture,
      and farmers are forced to grow a reduced number of species, dealing with a secure
      albeit low-market income. The introduction of medicinal and aromatic plants
      (MAPs) inside the current farming systems could represent a useful means to meet
      the multifunctional role of agriculture: producing safe food, in respect of the
      environment, and contributing to the development of rural areas. The study of the
      relationships between MAPs and the soils in which they may be grown may have two
      approaches: (1) the evaluation of yield and qualitative response of MAPs to the
      variation of soil features; and (2) the study of selective recovery of certain
      elements (toxic and beneficial), and their subsequent release in herbal products.
      In many MAPs, significant variations of plant characteristics have been
      ascertained with varying soil traits, and the selective recovery and subsequent
      release in food of certain elements have been demonstrated. Hence, great
      attention must be paid to the choice of soil and cropping strategies, to obtain
      satisfactory yields of high quality and best-priced products, respecting their
      safety and nutritional value.

PMID- 22419103
TI  - Changes in bacterial community structure of agricultural land due to long-term
      organic and chemical amendments.
AB  - Community level physiological profiling and pyrosequencing-based analysis of the
      V1-V2 16S rRNA gene region were used to characterize and compare microbial
      community structure, diversity, and bacterial phylogeny from soils of chemically
      cultivated land (CCL), organically cultivated land (OCL), and fallow grass land
      (FGL) for 16 years and were under three different land use types. The entire
      dataset comprised of 16,608 good-quality sequences (CCL, 6,379; OCL, 4,835; FGL,
      5,394); among them 12,606 sequences could be classified in 15 known phylum. The
      most abundant phylum were Proteobacteria (29.8%), Acidobacteria (22.6%),
      Actinobacteria (11.1%), and Bacteroidetes (4.7%), while 24.3% of the sequences
      were from bacterial domain but could not be further classified to any known
      phylum. Proteobacteria, Bacteroidetes, and Gemmatimonadetes were found to be
      significantly abundant in OCL soil. On the contrary, Actinobacteria and
      Acidobacteria were significantly abundant in CCL and FGL, respectively. Our
      findings supported the view that organic compost amendment (OCL) activates
      diverse group of microorganisms as compared with conventionally used synthetic
      chemical fertilizers. Functional diversity and evenness based on carbon source
      utilization pattern was significantly higher in OCL as compared to CCL and FGL,
      suggesting an improvement in soil quality. This abundance of microbes possibly
      leads to the enhanced level of soil organic carbon, soil organic nitrogen, and
      microbial biomass in OCL and FGL soils as collated with CCL. This work increases
      our current understanding on the effect of long-term organic and chemical
      amendment applications on abundance, diversity, and composition of bacterial
      community inhabiting the soil for the prospects of agricultural yield and
      quantity of soil.

PMID- 22419104
TI  - Recombination, diversity and allele sharing of infectivity proteins between
      Bartonella species from rodents.
AB  - The alpha-Proteobacterium Bartonella is a common parasite of voles and mice,
      giving rise to short-lived (4 weeks to 2 months) infections. Here, we report high
      sequence diversity in genes of the VirB/VirD type IV secretion system (T4SS),
      amongst Bartonella from natural rodent populations in NE Poland. The VirB5
      protein is predicted to consist of three conserved alpha helices separated by
      loops of variable length which include numerous indels. The C-terminal domain
      includes repeat stretches of KEK residues, reflecting underlying homopolymeric
      stretches of adenine residues. A total of 16 variants of VirB5, associated with
      host identity, but not bacterial taxon, were identified from 22 Bartonella
      isolates. One was clearly a recombinant from two others, another included an
      insertion of two KEK repeats. The virB5 gene appears to evolve via both mutation
      and recombination, as well as slippage mediated insertion/deletion events. The
      recombinational units are thought to be relatively short, as there was no
      evidence of linkage disequilibrium between virB5 and the bepA locus only 5.5 kb
      distant. The diversity of virB5 is assumed to be related to immunological role of
      this protein in Bartonella infections; diversity of virB5 may assist persistence
      of Bartonella in the rodent population, despite the relatively short (3-4 weeks)
      duration of individual infections. It is clear from the distribution of virB5 and
      bepA alleles that recombination within and between clades is widespread, and
      frequently crosses the boundaries of conventionally recognised Bartonella
      species.

PMID- 22419105
TI  - An EST-derived SNP and SSR genetic linkage map of cassava (Manihot esculenta
      Crantz).
AB  - Cassava (Manihot esculenta Crantz) is one of the most important food security
      crops in the tropics and increasingly being adopted for agro-industrial
      processing. Genetic improvement of cassava can be enhanced through marker
      assisted breeding. For this, appropriate genomic tools are required to dissect
      the genetic architecture of economically important traits. Here, a genome-wide
      SNP-based genetic map of cassava anchored in SSRs is presented. An outbreeder
      full-sib (F1) family was genotyped on two independent SNP assay platforms: an
      array of 1,536 SNPs on Illumina's GoldenGate platform was used to genotype a
      first batch of 60 F1. Of the 1,358 successfully converted SNPs, 600 which were
      polymorphic in at least one of the parents and was subsequently converted to
      KBiosciences' KASPar assay platform for genotyping 70 additional F1. High
      precision genotyping of 163 informative SSRs using capillary electrophoresis was
      also carried out. Linkage analysis resulted in a final linkage map of 1,837 centi
      Morgans (cM) containing 568 markers (434 SNPs and 134 SSRs) distributed across 19
      linkage groups. The average distance between adjacent markers was 3.4 cM. About
      94.2% of the mapped SNPs and SSRs have also been localized on scaffolds of
      version 4.1 assembly of the cassava draft genome sequence. This more saturated
      genetic linkage map of cassava that combines SSR and SNP markers should find
      several applications in the improvement of cassava including aligning scaffolds
      of the cassava genome sequence, genetic analyses of important agro-morphological
      traits, studying the linkage disequilibrium landscape and comparative genomics.

PMID- 22419106
TI  - A novel gene IBF1 is required for the inhibition of brown pigment deposition in
      rice hull furrows.
AB  - The role of flavonoids as the major red, blue, purple and brown pigments in
      plants has gained these secondary products a great deal of attention over the
      years. In this study, we characterized a rice inhibitor for brown furrows1 (ibf1)
      mutant. In the ibf1 mutant, brown pigments specifically accumulate in hull
      furrows during seed maturation and reach a maximum level in dry seeds. Higher
      amounts of total flavonoids and anthocyanin in hull may be responsible for the
      brown pigmentation of ibf1. The IBF1 gene, which encodes a similar kelch repeat
      containing F-box protein, was isolated by map-based cloning approach. Real-time
      RT-PCR and GUS activity assays revealed that IBF1 specifically expressed in
      reproductive tissues. GFP-IBF1 fusion protein mainly localized in cytoplasm. The
      expression of some major structural enzymatic genes involved in flavonoids
      biosynthesis could be up- or down-regulated to some different extent in ibf1
      mutant. Our data suggested that IBF1 as a suppressor could inhibit the brown
      pigmentation of rice hull furrows.

PMID- 22419107
TI  - Phosphorylation of serine 774 of the neural cell adhesion molecule is necessary
      for cyclic adenosine monophosphate response element binding protein activation
      and neurite outgrowth.
AB  - The neural cell adhesion molecule (NCAM) plays a fundamental role during
      development and regeneration. NCAM is expressed in three major isoforms, two of
      them with intracellular domains of different length and one without any
      intracellular domain. The cytoplasmic domain of NCAM contains, depending on the
      isoform, up to 49 phosphorylation sites, and it has been demonstrated previously
      by phosphoproteomic analysis that NCAM is phosphorylated on serine 774. However,
      the impact of NCAM phosphorylation is unclear. Here we have analyzed the
      phosphorylation of serine 774 in more detail and found that phosphorylation of
      this site is crucial for NCAM-mediated signal transduction. A serine-to-alanine
      exchange at position 774 (NCAM140-S774A) resulted in decreased activation of the
      cAMP response element binding protein (CREB) after NCAM stimulation and, as a
      consequence, in decreased neurite outgrowth of NCAM140-S774A-transfected B35
      neuroblastoma cells.

PMID- 22419108
TI  - GLP-1 response to a mixed meal: what happens 10 years after Roux-en-Y gastric
      bypass (RYGB)?
AB  - BACKGROUND: Oral meal consumption increases glucagon-like peptide 1 (GLP-1)
      release which maintains euglycemia by increasing insulin secretion. This effect
      is exaggerated during short-term follow-up of Roux-en-y gastric bypass (RYGB). We
      examined the durability of this effect in patient with type 2 diabetes (T2DM) >10
      years after RYGB. METHODS: GLP-1 response to a mixed meal in the 10-year post
      RYGB group (n = 5) was compared to lean (n = 9), obese (n = 6), and type 2
      diabetic (n = 10) controls using a cross-sectional study design. Analysis of
      variance (ANOVA) was used to evaluate GLP-1 response to mixed meal consumption
      from 0 to 300 min, 0-20 min, 20-60 min, and 60-300 min, respectively. Weight,
      insulin resistance, and T2DM were also assessed. RESULTS: GLP-1 response 0-300
      min in the 10-year post-RYGB showed a statistically significant overall
      difference (p =  0.01) compared to controls. Furthermore, GLP-1 response 0-20 min
      in the 10-year post-RYGB group showed a very rapid statistically significant rise
      (p = 0.035) to a peak of 40 pM. GLP-1 response between 20 and 60 min showed a
      rapid statistically significant (p = 0.041) decline in GLP-1 response from ~40 pM
      to 10 pM. GLP-1 response in the 10-year post-RYGB group from 60 to 300 min showed
      no statistically significant difference from controls. BMI, HOMA, and fasting
      serum glucose before and >10 years after RYGB changed from 59.9 -> 40.4, 8.7 ->
      0.88, and 155.2 -> 87.6 mg/dl, respectively, and were statistically significant
      (p < 0.05). CONCLUSIONS: An exaggerated GLP-1 response was noted 10 years after
      RYGB, strongly suggesting a durability of this effect. This phenomenon may play a
      key role in maintaining type 2 diabetes remission and weight loss after RYGB.

PMID- 22419110
TI  - Stabilization of ribozyme-like cis-noncoding rRNAs induces apoptotic and
      nonapoptotic death in lung cells.
AB  - Bidirectional non-protein-coding RNAs are ubiquitously transcribed from the
      genome. Convergent sense and antisense transcripts may regulate each other. Here,
      we examined the convergent cis-noncoding rRNAs (nc-rRNAs) in A5 and E9 lung
      cancer models. Sense nc-rRNAs extending from rDNA intergenic region to internal
      transcribed spacer of around 10 kb in length were identified. nc-rRNAs in sense
      direction exhibited in vitro characteristics of ribozymes, namely, degradation
      upon incubation with MgCl(2) and stabilization by complementary oligonucleotides.
      Detection of endogenous cleavage-ligation products carrying internal deletion of
      hundreds to thousands nucleotides by massively parallel sequencing confirmed the
      catalytic properties. Transfection of oligonucleotides pairing with antisense nc
      rRNAs stabilized both target and complementary transcripts, perturbed rRNA
      biogenesis, and induced massive cell death via apoptotic and/or nonapoptotic
      mechanisms depending on cell type and treatment. Oligonucleotides targeting
      cellular sense transcripts are less responsive. Spontaneously detached cells,
      though rare, also showed accumulation of nc-rRNAs and perturbation of rRNA
      biogenesis. Direct participation of nc-rRNAs in apoptotic and nonapoptotic death
      was demonstrated by transfection of synthetic nc-rRNAs encompassing the rDNA
      promoter. In sum, convergent cis-nc-rRNAs follow a feed-forward mechanism to
      regulate each other and rRNA biogenesis. This opens an opportunity to disrupt
      rRNA biogenesis, commonly upregulated in cancers, via inhibition of ribozyme-like
      activities in nc-rRNAs.

PMID- 22419109
TI  - C16 ceramide is crucial for triacylglycerol-induced apoptosis in macrophages.
AB  - Triacylglycerol (TG) accumulation caused by adipose triglyceride lipase (ATGL)
      deficiency or very low-density lipoprotein (VLDL) loading of wild-type (Wt)
      macrophages results in mitochondrial-mediated apoptosis. This phenotype is
      correlated to depletion of Ca(2+) from the endoplasmic reticulum (ER), an event
      known to induce the unfolded protein response (UPR). Here, we show that ER stress
      in TG-rich macrophages activates the UPR, resulting in increased abundance of the
      chaperone GRP78/BiP, the induction of pancreatic ER kinase-like ER kinase,
      phosphorylation and activation of eukaryotic translation initiation factor 2A,
      the translocation of activating transcription factor (ATF)4 and ATF6 to the
      nucleus and the induction of the cell death executor CCAAT/enhancer-binding
      protein homologous protein. C16:0 ceramide concentrations were increased in Atgl
      /- and VLDL-loaded Wt macrophages. Overexpression of ceramide synthases was
      sufficient to induce mitochondrial apoptosis in Wt macrophages. In accordance,
      inhibition of ceramide synthases in Atgl-/- macrophages by fumonisin B1 (FB1)
      resulted in specific inhibition of C16:0 ceramide, whereas intracellular TG
      concentrations remained high. Although the UPR was still activated in Atgl-/-
      macrophages, FB1 treatment rescued Atgl-/- macrophages from mitochondrial
      dysfunction and programmed cell death. We conclude that C16:0 ceramide elicits
      apoptosis in Atgl-/- macrophages by activation of the mitochondrial apoptosis
      pathway.

PMID- 22419111
TI  - HIV-1 Tat protein directly induces mitochondrial membrane permeabilization and
      inactivates cytochrome c oxidase.
AB  - The Trans-activator protein (Tat) of human immunodeficiency virus (HIV) is a
      pleiotropic protein involved in different aspects of AIDS pathogenesis. As a
      number of viral proteins Tat is suspected to disturb mitochondrial function. We
      prepared pure synthetic full-length Tat by native chemical ligation (NCL), and
      Tat peptides, to evaluate their direct effects on isolated mitochondria.
      Submicromolar doses of synthetic Tat cause a rapid dissipation of the
      mitochondrial transmembrane potential (DeltaPsi(m)) as well as cytochrome c
      release in mitochondria isolated from mouse liver, heart, and brain. Accordingly,
      Tat decreases substrate oxidation by mitochondria isolated from these tissues,
      with oxygen uptake being initially restored by adding cytochrome c. The anion
      channel inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)
      protects isolated mitochondria against Tat-induced mitochondrial membrane
      permeabilization (MMP), whereas ruthenium red, a ryanodine receptor blocker, does
      not. Pharmacologic inhibitors of the permeability transition pore, Bax/Bak
      inhibitors, and recombinant Bcl-2 and Bcl-XL proteins do not reduce Tat-induced
      MMP. We finally observed that Tat inhibits cytochrome c oxidase (COX) activity in
      disrupted mitochondria isolated from liver, heart, and brain of both mouse and
      human samples, making it the first described viral protein to be a potential COX
      inhibitor.

PMID- 22419112
TI  - Nucleolar protein CSIG is required for p33ING1 function in UV-induced apoptosis.
AB  - Cellular senescence-inhibited gene (CSIG) protein, a nucleolar protein with a
      ribosomal L1 domain in its N-terminus, can exert non-ribosomal functions to
      regulate biological processes, such as cellular senescence. Here, we describe a
      previously unknown function for CSIG: promotion of apoptosis in response to
      ultraviolet (UV) irradiation-induced CSIG upregulation. We identified p33ING1 as
      a binding partner that interacts with CSIG. After UV irradiation, p33ING1
      increases its protein expression, translocates into the nucleolus and binds CSIG.
      p33ING1 requires its nucleolar targeting sequence region to interact with CSIG
      and enhance CSIG protein stability, which is essential for activation of
      downstream effectors, Bcl-2-associated X protein, to promote apoptosis. Thus, our
      data imply that p33ING1-CSIG axis functions as a novel pro-apoptotic regulator in
      response to DNA damage.

PMID- 22419113
TI  - FTS and 2-DG induce pancreatic cancer cell death and tumor shrinkage in mice.
AB  - The Ras inhibitor S-trans-trans farnesylthiosalicylic acid (FTS) inhibits active
      Ras, which controls cell proliferation, differentiation, survival, and
      metabolism. FTS also inhibits HIF1alpha expression in cancer cells, leading to an
      energy crisis. The synthetic glucose analog 2-deoxy-D-glucose (2-DG), which
      inhibits glycolysis, is selectively directed to tumor cells that exhibit
      increased glucose consumption. The 2-DG enters tumor cells, where it competes
      with glucose for glycolytic enzymes. In cancer models, as well as in human phase
      1 trials, 2-DG inhibits tumor growth without toxicity. We postulated that under
      normoxic conditions, tumor cells treated with FTS would be more sensitive than
      normal cells to 2-DG. We show here that combined treatment with FTS and 2-DG
      inhibited cancer cell proliferation additively, yet induced apoptotic cell death
      synergistically both in vitro and in vivo. The induced apoptosis was inferred
      from QVD-OPH inhibition, an increase in cleaved caspase 3, and loss of survivin.
      FTS and 2-DG when combined, but not separately, also induced an increase in
      fibrosis of the tumor tissue, chronic inflammation, and tumor shrinkage. Overall,
      these results suggest a possible new treatment of pancreatic tumors by the
      combined administration of FTS and 2-DG, which together induce pancreatic tumor
      cell death and tumor shrinkage under non-toxic conditions.

PMID- 22419115
TI  - Re-oxygenation causes hypoxic tumor regression through restoration of p53 wild
      type conformation and post-translational modifications.
AB  - Hypoxic tumors are resistant to conventional therapies through indirect
      mechanisms such as the selection of resistant phenotype under chronic hypoxia.
      Hyperbaric oxygen (HBO) therapy has been shown to increase oxygen level and
      induce apoptosis in hypoxic tumor. However, it could produce significant adverse
      effects including oxygen toxic seizures and severe radiation tissue injury due to
      high pressure. We have shown that repeated oxygenation at 30% O(2) (1 atmospheres
      absolute) results in significant regression of MCF-7 tumor xenografts without any
      adverse effect. In MCF-7 cells, re-oxygenation showed an eightfold increase in
      cellular apoptosis. Both in hypoxic tumor and in hypoxic cells, that exclusively
      favor p53 to exist in mutant conformation, re-oxygenation restores p53 wild-type
      conformation. The oxygen-mediated rescue of mutant p53 followed by its trans
      activation is responsible for the induction of p53-downstream apoptotic, cell
      cycle arrest and DNA-repair genes. Further, p53 trans-activation may thus be due
      to its post-translational modifications as a result of re-oxygenation. We have
      thus concluded that oxygen therapy without pressure, as opposed to HBO therapy,
      may be ideal for hypoxic tumor regression, which functions through oxygen
      mediated rescue of mutant p53 followed by induction of apoptosis.

PMID- 22419114
TI  - Regulation of p73 activity by post-translational modifications.
AB  - The transcription factor p73 is a member of the p53 family that can be expressed
      as at least 24 different isoforms with pro- or anti-apoptotic attributes. The
      TAp73 isoforms are expressed from an upstream promoter and are regarded as bona
      fide tumor suppressors; they can induce cell cycle arrest/apoptosis and protect
      against genomic instability. On the other hand, DeltaNp73 isoforms lack the N
      terminus transactivation domain; hence, cannot induce the expression of pro
      apoptotic genes, but still can oligomerize with TAp73 or p53 to block their
      transcriptional activities. Therefore, the ratio of TAp73 isoforms to DeltaNp73
      isoforms is critical for the quality of the response to a genomic insult and
      needs to be delicately regulated at both transcriptional and post-translational
      level. In this review, we will summarize the current knowledge on the post
      translational regulatory pathways involved to keep p73 protein under control. A
      comprehensive understanding of p73 post-translational modifications will be
      extremely useful for the development of new strategies for treating and
      preventing cancer.

PMID- 22419116
TI  - Mucus clearance, MyD88-dependent and MyD88-independent immunity modulate lung
      susceptibility to spontaneous bacterial infection and inflammation.
AB  - It has been postulated that mucus stasis is central to the pathogenesis of
      obstructive lung diseases. In Scnn1b-transgenic (Scnn1b-Tg+ mice, airway-targeted
      overexpression of the epithelial Na+ channel beta subunit causes airway surface
      dehydration, which results in mucus stasis and inflammation. Bronchoalveolar
      lavage from neonatal Scnn1b-Tg+ mice, but not wild-type littermates, contained
      increased mucus, bacteria, and neutrophils, which declined with age. Scnn1b-Tg+
      mice lung bacterial flora included environmental and oropharyngeal species,
      suggesting inhalation and/or aspiration as routes of entry. Genetic deletion of
      the Toll-interleukin-1 receptor adapter molecule MyD88 in Scnn1b-Tg+ mice did not
      modify airway mucus obstruction, but caused defective neutrophil recruitment and
      increased bacterial infection, which persisted into adulthood. Scnn1b-Tg+ mice
      derived into germ-free conditions exhibited mucus obstruction similar to
      conventional Scnn1b-Tg+ mice and sterile inflammation. Collectively, these data
      suggest that dehydration-induced mucus stasis promotes infection, compounds
      defects in other immune mechanisms, and alone is sufficient to trigger airway
      inflammation.

PMID- 22419117
TI  - Automatic detection of a prefrontal cortical response to emotionally rated music
      using multi-channel near-infrared spectroscopy.
AB  - Emotional responses can be induced by external sensory stimuli. For severely
      disabled nonverbal individuals who have no means of communication, the decoding
      of emotion may offer insight into an individual's state of mind and his/her
      response to events taking place in the surrounding environment. Near-infrared
      spectroscopy (NIRS) provides an opportunity for bed-side monitoring of emotions
      via measurement of hemodynamic activity in the prefrontal cortex, a brain region
      known to be involved in emotion processing. In this paper, prefrontal cortex
      activity of ten able-bodied participants was monitored using NIRS as they
      listened to 78 music excerpts with different emotional content and a control
      acoustic stimuli consisting of the Brown noise. The participants rated their
      emotional state after listening to each excerpt along the dimensions of valence
      (positive versus negative) and arousal (intense versus neutral). These ratings
      were used to label the NIRS trial data. Using a linear discriminant analysis
      based classifier and a two-dimensional time-domain feature set, trials with
      positive and negative emotions were discriminated with an average accuracy of
      71.94% +/- 8.19%. Trials with audible Brown noise representing a neutral response
      were differentiated from high arousal trials with an average accuracy of 71.93%
      +/- 9.09% using a two-dimensional feature set. In nine out of the ten
      participants, response to the neutral Brown noise was differentiated from high
      arousal trials with accuracies exceeding chance level, and positive versus
      negative emotional differentiation accuracies exceeded the chance level in seven
      out of the ten participants. These results illustrate that NIRS recordings of the
      prefrontal cortex during presentation of music with emotional content can be
      automatically decoded in terms of both valence and arousal encouraging future
      investigation of NIRS-based emotion detection in individuals with severe
      disabilities.

PMID- 22419118
TI  - Selective thioether macrocyclization of peptides having the N-terminal 2
      chloroacetyl group and competing two or three cysteine residues in translation.
AB  - The mode of thioether macrocyclization of peptides containing an N-terminal 2
      chloroacetyl group and two or three competing cysteine residues at downstream
      positions has been extensively studied, leading to a strategy for designated
      formation of overlapping-bicyclic peptides or dumbbell-type bicyclic peptides.

PMID- 22419119
TI  - Reward system dysfunction in autism spectrum disorders.
AB  - Although it has been suggested that social deficits of autism spectrum disorders
      (ASDs) are related to reward circuitry dysfunction, very little is known about
      the neural reward mechanisms in ASD. In the current functional magnetic resonance
      imaging study, we investigated brain activations in response to both social and
      monetary reward in a group of children with ASD, relative to matched controls.
      Participants with ASD showed the expected hypoactivation in the mesocorticolimbic
      circuitry in response to both reward types. In particular, diminished activation
      in the nucleus accumbens was observed when money, but not when social reward, was
      at stake, whereas the amygdala and anterior cingulate cortex were hypoactivated
      within the ASD group in response to both rewards. These data indicate that the
      reward circuitry is compromised in ASD in social as well as in non-social, i.e.
      monetary conditions, which likely contributes to atypical motivated behaviour.
      Taken together, with incentives used in this study sample, there is evidence for
      a general reward dysfunction in ASD. However, more ecologically valid social
      reward paradigms are needed to fully understand, whether there is any domain
      specificity to the reward deficit that appears evident in ASD, which would be
      most consistent with the ASD social phenotype.

PMID- 22419120
TI  - Banding patterns in Drosophila melanogaster polytene chromosomes correlate with
      DNA-binding protein occupancy.
AB  - The most enigmatic feature of polytene chromosomes is their banding pattern, the
      genetic organization of which has been a very attractive puzzle for many years.
      Recent genome-wide protein mapping efforts have produced a wealth of data for the
      chromosome proteins of Drosophila cells. Based on their specific protein
      composition, the chromosomes comprise two types of bands, as well as interbands.
      These differ in terms of time of replication and specific types of proteins. The
      interbands are characterized by their association with "active" chromatin
      proteins, nucleosome remodeling, and origin recognition complexes, and so they
      have three functions: acting as binding sites for RNA pol II, initiation of
      replication and nucleosome remodeling of short fragments of DNA. The borders and
      organization of the same band and interband regions are largely identical,
      irrespective of the cell type studied. This demonstrates that the banding pattern
      is a universal principle of the organization of interphase polytene and non
      polytene chromosomes.

PMID- 22419121
TI  - Pesticide use and fatal injury among farmers in the Agricultural Health Study.
AB  - PURPOSE: To assess whether pesticide use practices were associated with injury
      mortality among 51,035 male farmers from NC and IA enrolled in the Agricultural
      Health Study. METHODS: We used Cox proportional hazards models adjusted for age
      and state to estimate fatal injury risk associated with self-reported use of 49
      specific pesticides, personal protective equipment, specific types of farm
      machinery, and other farm factors collected 1-15 years preceding death. Cause
      specific mortality was obtained through linkage to mortality registries. RESULTS:
      We observed 338 injury fatalities over 727,543 person-years of follow-up (1993
      2008). Fatal injuries increased with days/year of pesticide application, with the
      highest risk among those with 60+ days of pesticide application annually [hazard
      ratio (HR) = 1.87; 95% confidence interval (CI) = 1.10, 3.18]. Chemical-resistant
      glove use was associated with decreased risk (HR = 0.73; 95% CI = 0.58, 0.93),
      but adjusting for glove use did not substantially change estimates for individual
      pesticides or pesticide use overall. Herbicides were associated with fatal
      injury, even after adjusting for operating farm equipment, which was
      independently associated with fatal injury. Ever use of five of 18 herbicides
      (2,4,5-T, paraquat, alachlor, metribuzin, and butylate) were associated with
      elevated risk. In addition, 2,4-D and cyanazine were associated with fatal injury
      in exposure-response analyses. There was no evidence of confounding of these
      results by other herbicides. CONCLUSION: The association between application of
      pesticides, particularly certain herbicides, and fatal injuries among farmers
      should be interpreted cautiously but deserves further evaluation, with particular
      focus on understanding timing of pesticide use and fatal injury.

PMID- 22419122
TI  - Organocatalytic three-component cascade reaction for the synthesis of
      spiro[indeno[1,2-b]furan]-triones.
AB  - New methods for the synthesis of spiro compounds containing dihydrofuran and
      coumarin moieties from 3-bromo-4-hydroxycoumarins as cyclic alpha-halo compound
      based on a pyridinium-ylide-assisted three-component tandem reaction is
      investigated. To the best of our knowledge, employing cyclic alpha-halo compounds
      for the synthesis of dihydrofuran-fused coumarin via a pyridinium ylide has not
      been reported yet.

PMID- 22419123
TI  - Histone H3K14 and H4K8 hyperacetylation is associated with Escherichia coli
      induced mastitis in mice.
AB  - Mastitis is a multietiological complex disease, defined as inflammation of
      parenchyma of mammary glands. Bacterial infection is the predominant cause of
      mastitis, though fungal, viral and mycoplasma infections also have been reported.
      Based on the severity of the disease, mastitis can be classified into
      subclinical, clinical and chronic forms. Bacterial pathogens from fresh cow milk
      were isolated and classified by standard microbiological tests and multiplex PCR.
      Epidemiological studies have shown that Escherichia coli is the second largest
      mastitis pathogen after Staphylococcus aureus in India. Based on Enterobacterial
      Repetitive Intergenic Consensus (ERIC)-PCR profile and presence of virulence
      genes, a field isolate of E. coli was used for intramammary inoculation in
      lactating mice. Histopathological examination of hematoxylin and eosin stained
      sections showed severe infiltration of polymorphonuclear neutrophils, mononuclear
      inflammatory cells in the alveolar lumen and also in interstitial space, and
      necrosis of alveolar epithelial cells after 24 h. Western blot and
      immunohistochemical analysis of mice mammary tissues showed significant
      hyperacetylation at histone H3K14 residue of both mammary epithelial cells and
      migrated inflammatory cells. Quantitative real-time PCR and genome-wide gene
      expression profile in E. coli infected mice mammary tissue revealed differential
      expression of genes related to inflammation, immunity, antimicrobial peptide
      expression, acute phase response and oxidative stress response. Expression of
      milk proteins was also suppressed. ChIP assay from paraffinized tissues showed
      selective enrichment of acetylated histone H3K14 and H4K8 at the promoters of
      overexpressed genes. These data suggest that E. coli infection in mice mammary
      tissue leads to histone hyperacetylation at the promoter of immune genes, which
      is a pre-requisite for the expression of inflammatory genes in order to mount a
      drastic immune response.

PMID- 22419124
TI  - A human Polycomb isoform lacking the Pc box does not participate to PRC1
      complexes but forms protein assemblies and represses transcription.
AB  - Polycomb repression controls the expression of hundreds of genes involved in
      development and is mediated by essentially two classes of chromatin-associated
      protein complexes. The Polycomb repressive complex 2 (PRC2) trimethylates histone
      H3 at lysine 27, an epigenetic mark that serves as a docking site for the PRC1
      protein complex. Drosophila core PRC1 is composed of four subunits: Polycomb
      (Pc), Posterior sex combs (Psc), Polyhomeotic (Ph) and Sex combs extra (Sce).
      Each of these proteins has multiple orthologs in vertebrates, thus generating an
      enormous scope for potential combinatorial diversity. In particular, mammalian
      genomes encode five Pc family members: CBX2, CBX4, CBX6, CBX7 and CBX8. To
      complicate matters further, distinct isoforms might arise from single genes.
      Here, we address the functional role of the two human CBX2 isoforms. Owing to
      different polyadenylation sites and alternative splicing events, the human CBX2
      locus produces two transcripts: a 5-exon transcript that encodes the 532-amino
      acid CBX2-1 isoform that contains the conserved chromodomain and Pc box and a 4
      exon transcript encoding a shorter isoform, CBX2-2, lacking the Pc box but still
      possessing a chromodomain. Using biochemical approaches and a novel in vivo
      imaging assay, we show that the short CBX2-2 isoform lacking the Pc box, does not
      participate in PRC1 protein complexes, but self-associates in vivo and forms
      complexes of high molecular weight. Furthermore, the CBX2 short isoform is still
      able to repress transcription, suggesting that Polycomb repression might occur in
      the absence of PRC1 formation.

PMID- 22419125
TI  - Use of multilocus methylation-specific single nucleotide primer extension (MS
      SNuPE) technology in diagnostic testing for human imprinted loci.
AB  - A number of diseases have been found to be linked to aberrant methylation of
      specific genes. However, most of the routine diagnostic techniques to detect
      epigenetic disturbances are restricted to single loci. Additionally, a precise
      quantification of the methylation status is often hampered. A considerable
      fraction of patients with Silver-Russell syndrome, Beckwith-Wiedemann syndrome
      and transient neonatal diabetes mellitus exhibit loss of methylation at further
      imprinted loci in addition to the disease specific ones (multilocus methylation
      defects, MLMD). As the currently available tests are mainly focused on single
      imprinted loci on different chromosomes and thereby make the detection of
      multilocus methylation defects time-consuming and expensive, we established
      methylation-specific single nucleotide primer extension (MS-SNuPE) assays for a
      simultaneous quantification of methylation at multiple methylated loci. We chose
      loci generally affected in patients with MLMD. The method was validated by
      screening 66 individuals with known (epi)genetic disturbances. In comparison to
      other methylation-specific techniques, multilocus methylation-specific single
      nucleotide primer extension allows the quantitative analysis of numerous CpG
      islands of different loci in one assay and is, therefore, suitable for the
      simultaneous diagnostic testing for different congenital imprinting disorders in
      parallel, as well as for MLMD.

PMID- 22419126
TI  - ABCA1 gene promoter DNA methylation is associated with HDL particle profile and
      coronary artery disease in familial hypercholesterolemia.
AB  - High-density lipoproteins cholesterol (HDL-C) level, a strong coronary artery
      disease (CAD) clinical biomarker, shows significant interindividual variability.
      However, the molecular mechanisms involved remain mostly unknown. ATP-binding
      cassette A1 (ABCA1) catalyzes the cholesterol transfer from peripheral cells to
      nascent HDL particles. Recently, a differentially methylation region was
      identified in ABCA1 gene promoter locus, near the first exon. Therefore, we
      hypothesized that DNA methylation changes at ABCA1 gene locus is one of the
      molecular mechanisms involved in HDL-C interindividual variability. The study was
      conducted in familial hypercholesterolemia (FH), a monogenic disorder associated
      with a high risk of CAD . Ninety-seven FH patients (all p.W66G for the LDLR gene
      mutation and not under lipid-lowering treatment) were recruited and finely
      phenotyped for DNA methylation analyses at ABCA1 gene locus. ABCA1 DNA
      methylation levels were found negatively correlated with circulating HDL-C (r = 
      0.20; p = 0.05), HDL2-phospholipid levels (r = -0.43; p = 0.04), and with a trend
      for association with HDL peak particle size (r = -0.38; p = 0.08). ABCA1 DNA
      methylation levels were also found associated with prior history of CAD (CAD =
      40.2% vs. without CAD = 34.3%; p = 0.003). These results suggest that epigenetic
      changes within the ABCA1 gene promoter contribute to the interindividual
      variability in plasma HDL-C concentrations and are associated with CAD
      expression. These findings could change our understanding of the molecular
      mechanisms involved in the pathophysiological processes leading to CAD.

PMID- 22419127
TI  - Prenatal antiepileptic exposure associates with neonatal DNA methylation
      differences.
AB  - Antiepileptic drugs (AEDs) are used to treat a variety of neuropsychiatric
      illnesses commonly encountered in women during their reproductive years,
      including epilepsy and bipolar disorder. Despite their widespread use, the impact
      of prenatal exposure on fetal development remains obscure. To evaluate whether
      AEDs taken by pregnant mothers influence DNA methylation patterns in their
      neonates, DNA was extracted from the umbilical cord blood of 201 neonates whose
      mothers were treated for neuropsychiatric illness during pregnancy and
      interrogated across 27,578 CpG sites using the Illumina HumanMethylation27
      BeadChip. The association of each methylation value with the cumulative duration
      of prenatal AED exposure was examined using a linear mixed model. The average
      methylation level across all CpG sites was calculated for each subject, and this
      global methylation measure was evaluated similarly. Neonates with a longer
      duration of AED exposure in pregnancy showed a decrease in average global
      methylation (p = 0.0045). Further, DNA methylation of CpG sites in 14 genes
      significantly decreased with the duration of prenatal AED exposure even after
      adjusting for multiple comparisons (FDR < 0.05). For a small subset (n = 19) of
      these neonates, a second tissue, placenta, was available in addition to cord
      blood. Methylation of 3 of these 14 CpG sites was also significantly decreased in
      placental tissue. These novel data suggest decreased DNA methylation in neonates
      of mothers who took AEDs during pregnancy. The long-term stability and potential
      impact of these changes warrant further attention, and caution may be warranted
      before prescribing AEDs to pregnant women.

PMID- 22419128
TI  - SFRP1 CpG island methylation locus is associated with renal cell cancer
      susceptibility and disease recurrence.
AB  - Loss of the secreted Fzd-related protein 1 (SFRP1) and concurrent alteration of
      the SFRP1/WNT pathway are frequently observed in human cancers such as in renal
      cell cancer (RCC). Whether methylation of a SFRP1 CpG island locus in normal
      human solid tissues is associated with increased tissue specific cancer risk has
      not been determined to date. Here we measure the cancer risk attributable to
      SFRP1 DNA methylation in renal tissue. Pyrosequencing of bisulfite treated DNA
      was used for a case-control study including 120 normal-appearing renal tissues of
      autopsy specimens and 72 normal-appearing tissues obtained from tumor adjacent
      areas, and a cross sectional study of 96 RCCs. Association of methylation with
      demographic risk factor age, clinicopathological parameters and course of
      patients was investigated. We show significant hypermethylation of a SFRP1 CpG
      island locus in normal-appearing renal tissues from RCC patients compared with
      normal-appearing autopsy kidney tissues. Inter quartile analysis revealed a 6-,
      13- and 11-fold increased cancer risk for the second, third and fourth quartiles
      of methylation in the age matched subgroup of tissues (p = 0.001, p = 1.3E-6, p =
      6.9E-6). Methylation in autopsy tissues increased with age and methylation in
      tumors was an independent predictor of recurrence free survival. SFRP1 DNA
      methylation, accumulates with age in normal-appearing kidney tissues and is
      associated with increased renal cancer risk, suggesting this CGI sub region as an
      epigenetic susceptibility locus for RCC. Our data underline the need to further
      analyze the tissue specific risks conferred by methylated loci for the
      development of human cancers.

PMID- 22419129
TI  - Alteration of DNA demethylation dynamics by in vitro culture conditions in rabbit
      pre-implantation embryos.
AB  - Alterations to DNA methylation have been attributed to in vitro culture and may
      affect normal embryo development. We chose to analyze DNA methylation
      reprogramming in the rabbit which, of the species with delayed transcriptional
      activation of the embryonic genome, allows easy comparisons between in vivo
      developed (IVD) and in vitro-cultured (IVC) embryos. In this species, variations
      in DNA methylation had not previously been quantified, even in IVD embryos. IVD
      and IVC embryos were recovered at the 2, 4, 8 and 16-cell, morula and blastocyst
      stages. Immunostaining for 5-methyl-cytidine and normalization of the quantity of
      methylated DNA vs. the total DNA content were then performed. Our quantitative
      results evidenced DNA demethylation during pre-implantation development in both
      IVD and IVC embryos, but with different kinetics. Demethylation occurred earlier
      in vitro than in vivo between the 2 and 8-cell stages in IVC embryos, reaching
      its lowest level, while it only started at the 4-cell stage and ended at the 16
      cell stage in IVD embryos. We also showed that an absence of serum from the
      culture medium significantly altered the degree of DNA demethylation. Finally, at
      the blastocyst stage, ICM was more methylated than the trophectoderm in all
      cases. Despite a morphological delay observed in in vitro cultured blastocysts,
      the difference in DNA methylation between ICM and trophectoderm cells appeared at
      the same time post-fertilization in IVD and IVC embryos, which may reflect
      another difference in the dynamics of DNA methylation during blastocyst
      formation. Our data thus clearly establish an effect of embryonic environment on
      DNA methylation reprogramming during pre-implantation development in a non-rodent
      species.

PMID- 22419130
TI  - High-throughput micro plate assays for screening flavonoid content and DPPH
      scavenging activity in sorghum bran and flour.
AB  - BACKGROUND: Sorghum possesses phenolic compounds that are health-promoting
      constituents of the grain. There are approximately 40 000 sorghum accessions,
      many of which have not been evaluated for the grain's health-promoting potential.
      Conventional methods for measuring total phenolic content, flavonoid content and
      2,2-diphenyl-1-picrylhydrazyl (DPPH)-scavenging capacity are time-consuming and
      labour-intensive, resulting in low overall throughput. The objective of this
      study was to develop a high-throughput screening assay for large sorghum sample
      sets to determine flavonoid and phenolic content and to modify existing DPPH and
      total phenolic assays. RESULTS: The 96-well assays exhibited a correlation of >
      0.9 with the conventional assays. The 96-well assays allowed for up to 64 samples
      to be run per day compared with 20-24 samples (depending on the test) for the
      conventional methods. The 96-well assays had excellent accuracy (97.65-106.16%
      recovery), precision (1.06-8.28% coefficient of variation (CV)) and
      reproducibility (1.32-2.13% CV inter-day and 1.36-2.09% CV intra-day).
      CONCLUSION: The high-throughput 96-well plate method proved to be as robust and
      reproducible as the conventional method for determining total phenolic content,
      flavonoid content and DPPH-scavenging capacity in either sorghum bran or flour.

PMID- 22419131
TI  - Morphology of a new deep-sea acorn worm (class Enteropneusta, phylum
      Hemichordata): a part-time demersal drifter with externalized ovaries.
AB  - Ten individuals of an enteropneust in the family Torquaratoridae were videotaped
      between 2,900 and 3,500 m in the Eastern Pacific--one drifting a few centimeters
      above the bottom, two exposed on the substrate, and seven partly burrowed,
      reflecting a bentho-pelagic life style. Here, we describe a captured specimen (26
      cm living length) as the holotype of Allapasus aurantiacus n. gen., n. sp. The
      small proboscis is dome-shaped, and the collar is only slightly wider than deep;
      both of these body regions are more muscular than in other torquaratorids, which
      presumably facilitates burrowing. The proboscis complex, in contrast to that of
      shallow-living enteropneusts, lacks a pericardial sac and is located relatively
      posteriorly in the proboscis stalk. The stomochord is separated from the main
      course of the gut by the intervention of a small, plate-like proboscis skeleton
      lacking posterior horns. The most anterior region of the trunk houses the
      pharynx, in which the pharyngeal skeletal bars are not connected by synapticles.
      The postpharyngeal trunk comprises three intestinal regions: prehepatic, hepatic
      (with conspicuous sacculations), and posthepatic. On either side of the worm, a
      flap of body wall (lateral wing) runs the entire length of the trunk. The two
      lateral wings can wrap the body so their edges meet in the dorsal midline,
      although they often gape open along the pharyngeal region. The holotype is a
      female (presumably the species is gonochoric) with numerous ovaries located in
      the lateral wings along the pharyngeal region. Each larger ovary contains a
      single primary oocyte (up to 1,500 MUm in diameter) and bulges outwards in an
      epidermal pouch attached to the rest of the body by a slender stalk. Such
      externalized ovaries are unprecedented in any animal, and nothing is yet known of
      their role in the reproductive biology of A. aurantiacus.

PMID- 22419133
TI  - [Comment on CME ultrasound diagnosis 43, "Lump in the neck"].

PMID- 22419132
TI  - Sublethal effects of atrazine on embryo-larval development of Rhinella arenarum
      (Anura: Bufonidae).
AB  - Atrazine (ATR), one of the most widely used herbicides in the world, affects not
      only target organisms but also the biota in general. Here, the teratogenic and
      neurotoxic effects of ATR on Rhinella arenarum (South American toad) embryos, and
      larvae were evaluated by means of standardized bioassays during acute and chronic
      exposures. The herbicide had a significant incidence of malformations, with a
      Teratogenic Index (TI) of 3.28. The main effects were delayed development,
      reduced body size, microcephaly, axial flexures, wavy tail and edema. In
      addition, delayed development, reduced development of forelimbs, and edema were
      recorded at metamorphosis stages. Scanning electron microscopy allowed observing
      different degrees of cellular dissociation and persistent cilliar cells in
      specific regions like the adhesive structure and tail fin. Results obtained by
      ATR 24 h pulse exposures at six developmental stages pointed out blastula as the
      most susceptible developmental stage both for immediate and delayed adverse
      effects. A noteworthy recovery capacity from acute toxic effects was recorded
      from the neural plate stage onwards. Regarding neurotoxic effects, abnormal, and
      erratic swimming and spasmodic contractions were recorded. Both the teratogenic
      and neurotoxic effects reported in this study demonstrate the importance of
      evaluating sublethal effects in non-target organisms as they could imply reduced
      fitness of individuals and eventually a population decline. The Hazard Quotients
      (HQ) for ATR ranged from 0.14 to 10.80, and the fact that some of these values
      are above USEPA's level of concern indicate that ATR is likely a risk to R.
      arenarum.

PMID- 22419134
TI  - [Interaction of drugs with the primary disease - when medicines exacerbate
      illnesses].

PMID- 22419135
TI  - [Diclofenac induced liver injuries].
AB  - We report the case of an 83-year-old female patient who developed diclofenac
      associated liver injury nine days after therapy had started. Diclofenac was used
      to treat back pain associated with an acute exacerbation of a chronic
      lumbovertebral symptoms reversed. We discuss the adverse reaction profile of
      diclofenac, particularly diclofenac-induced liver injury. We also discuss the
      epidemiology, clinical presentation and mechanisms of NSAID-induced liver injury,
      as well as risk factors and preventive measures.

PMID- 22419136
TI  - [Dosis sola facit venenum: outcome of intoxications in a Swiss university
      hospital].
AB  - Poisoning is a frequent disease in an emergency division. During four years we
      observed patients with poisoning related to there reason of intoxication, the
      degree of severity, age group and sex, and tried to make conclusions about lethal
      outcome on behalf of our data. The severity was defined by the "poison severity
      scale" (PSS). 1515 patients with intoxication in four years were documented. 152
      (10%) of them had a severe intoxication or lethal outcome. In women suicide
      predominated as reason of severe intoxication, whereas in men an abuse of alcool
      and drugs was mostly seen. A multidisciplinary approach is important for handling
      intoxicated patients. Our investigation showed a good somatical outcome of
      patients with severe intoxication. Mortality was 5% (7/152 patients).

PMID- 22419137
TI  - [Management of transient ischemic attack (TIA) and acute stroke].
AB  - Patients with a transient ischemic attack and an acute stroke need urgent
      investigations and therapy in a stroke unit. Immediate investigation of the
      etiology and early secondary prevention measures reduce the likelihood of
      recurrent and other vascular events. In selected stroke patients intravenous
      thrombolysis and/or endovascular therapies lead to a significant reduction of
      long term disabilities.

PMID- 22419138
TI  - [Skin and soft tissue infections].
AB  - Skin- and Soft tissue infections are a frequent problem in hospital as well as in
      ambulatory care. Diagnostic procedures and treatment principles have to include
      the most frequent pathogens. While the acute forms of skin and soft tissue
      infections, with, necrotising fasciitis as important exception, rarely cause
      diagnostic or therapeutic problem, the treatment of patients with recurrent
      furunculosis, chronic wounds and diabetic feet is often difficult and frustration
      for patients and physicians. This article gives an overview of the most important
      problems and treatment strategies.

PMID- 22419139
TI  - [Aortic isthmus stenosis in newborn infants].

PMID- 22419140
TI  - [Fractures associated with dimonshed bone density, thypercalciuria and
      osteolysis. Is the diagnosis an osteoporosis or a syndrome?].
AB  - At first osteomalacia was presumed clinically and radiologically in a 49-year old
      female patient. Radiologically there were multiple suspected neoplastic osseous
      infiltrations, which was not confirmed by subsequent investigations. There were
      no indications of osteomalacia or malabsorption in the laboratory exams. The
      multiple microfractures and osteolysis of the fingers, the toes, the wrist and
      the tarsus detected with varius imaging techniques were ascribed to an
      acroosteolysis. Osteoporosis of both femoral necks was also present in dual
      photon X-ray absorptiometry densitometry. Cheney Syndrom (HCS) was diagnosed
      clinically and radiologically and a treatment with bisphosphonates was
      introduced.

PMID- 22419141
TI  - [What vision loss might bring to light].
AB  - We report a case of a 36-year old patient who suffered from a unilateral painless
      loss of vision. Ophthalmological examination in the context of a highly reactive
      syphilis serology revealed an acute syphilitic posterior placoide chorioretinitis
      (ASPPC). Additional clinical findings were a mucosal lesion on the upper lip,
      consistent with a plaque opaline and an alopecia specifica as manifestation of
      secondary syphilis. Treatment consisted in 6 x 4 Mio. IE* Penicillin G for 14
      days and 50 mg Prednisone for five days to prevent a Jarisch Herxheimer reaction.
      The diagnostic measures, therapy and follow up of syphilis, focusing on ocular
      involvement, are described.

PMID- 22419142
TI  - [No effect of caudal epidural injections in patients with chronic lumbar
      radiculopathy].

PMID- 22419143
TI  - [Ibuprofen/paracetamol combination therapy is more effective than monotherapy in
      knee pain, but increases bleeding risk].

PMID- 22419148
TI  - Clinical picture of meningitis in the adult patient and its relationship with
      age.
AB  - To analyze the clinical characteristics of acute meningitis and their
      relationship with age in adult patients presenting to the emergency department.
      We retrospectively investigated consecutive adult patients admitted with a
      diagnosis of bacterial or viral meningitis from 2002 to 2006. Data about
      patient's history, symptoms and signs at presentation, etiology and clinical
      course were collected. To investigate the relationship of clinical presentation
      with age, we divided patients in four age quartiles (<30 years, between 30 and 36
      years, between 37 and 56 years, >56 years). Among the 202 patients considered in
      the study (mean age 42.8 +/- 18.7 years, range 14-90), 162 (80.2%) patients had
      viral and 40 (19.8%) bacterial meningitis. Specific signs, such as neck stiffness
      or Kernig or Brudzinski signs, were more common in the first than in the fourth
      quartile (73.1 vs. 45.7% P = 0.041). Conversely, altered consciousness expressed
      as Glasgow Coma Scale (GCS) <15 was more frequent in the fourth (80.4%) than in
      the first (9.6%) quartile (P < 0.001). The linear regression analysis confirmed a
      significant decrease of GCS with the increasing of patient's age (r = -0.69, P <
      0.001). At multivariate analysis, aging was associated with altered level of
      consciousness (OR 16.7, P < 0.001) independent of viral or bacterial etiology of
      the presence of comorbidities and of clinical severity (presence of severe sepsis
      or septic shock). Meningitis presentation largely differs with aging in adult
      patients. Level of consciousness is frequently altered in the older patients,
      when other specific signs become more rare, independent of etiology,
      comorbidities and clinical severity.

PMID- 22419147
TI  - A screening study of drug-drug interactions in cerivastatin users: an adverse
      effect of clopidogrel.
AB  - An analysis of a case-control study of rhabdomyolysis was conducted to screen for
      previously unrecognized cytochrome P450 enzyme (CYP) 2C8 inhibitors that may
      cause other clinically important drug-drug interactions. Medication use in cases
      of rhabdomyolysis using cerivastatin (n = 72) was compared with that in controls
      using atorvastatin (n = 287) for the period 1998-2001. The use of clopidogrel was
      strongly associated with rhabdomyolysis (odds ratio (OR) 29.6; 95% confidence
      interval (CI), 6.1-143). In a replication effort that used the US Food and Drug
      Administration (FDA) Adverse Event Reporting System (AERS), it was found that
      clopidogrel was used more commonly in patients with rhabdomyolysis receiving
      cerivastatin (17%) than in those receiving atorvastatin (0%, OR infinity; 95% CI
      = 5.2-infinity). Several medications were tested in vitro for their potential to
      cause drug-drug interactions. Clopidogrel, rosiglitazone, and montelukast were
      the most potent inhibitors of cerivastatin metabolism. Clopidogrel and its
      metabolites also inhibited cerivastatin metabolism in human hepatocytes. These
      epidemiological and in vitro findings suggest that clopidogrel may cause
      clinically important, dose-dependent drug-drug interactions with other
      medications metabolized by CYP2C8.

PMID- 22419149
TI  - Challenges in dealing with a cirrhotic patient.

PMID- 22419150
TI  - Cattle MHC nomenclature: is it possible to assign sequences to discrete class I
      genes?
AB  - The cattle major histocompatibility complex (MHC) region contains a variable
      number of classical class I genes encoding polymorphic molecules involved in
      antigen presentation. Six classical class I genes have been described, but
      assigning sequences to these genes has proved problematic. We propose a
      refinement of the existing nomenclature, which currently names the 97 known
      classical class I sequences in a single series. Phylogenetic analysis of the 3'
      portion of the coding region allows segregation of these into six groups; thus,
      we have prefixed existing names with the appropriate number. Although it is clear
      that some of these groups correspond to discrete genes, it is currently not
      possible to state definitively that all do. However, the main groupings are
      consistent, and in conjunction with other evidence, we feel it is now appropriate
      to rename the sequences accordingly. Segregation of sequences into groups in this
      way will facilitate ongoing research and future use of the cattle MHC section of
      the Immuno Polymorphism Database.

PMID- 22419151
TI  - Acarbose bioequivalence: exploration of new pharmacodynamic parameters.
AB  - To investigate bioequivalence (BE) testing of an acarbose formulation in healthy
      Chinese volunteers through the use of recommended and innovative pharmacodynamic
      (PD) parameters. Following the Food and Drug Administration (FDA) guidance, a
      randomized, cross-over study of acarbose test (T) and reference (R) (Glucobay(r))
      formulations was performed with a 1-week wash-out period. Preliminary pilot
      studies showed that the appropriate dose of acarbose was 2 * 50 mg, and the
      required number of subjects was 40. Serum glucose concentrations after sucrose
      administration (baseline) and co-administration of sucrose/acarbose on the
      following day were both determined. Three newly defined PD measures of glucose
      fluctuation (glucose excursion (GE), GE' (glucose excursion without the effect of
      the homeostatic glucose control), and fAUC (degree of fluctuation of serum
      glucose based on AUC)), the plateau glucose concentration (C(ss)), and time of
      maximum reduction in glucose concentration (T (max)) were tested in the
      evaluation. The adequacy of the two parameters recommended by the FDA,
      DeltaC(SG,max) (maximum reduction in serum glucose concentration) and AUEC((0
      4h)) (reduction in the AUC((0-4h)) of glucose between baseline and acarbose
      formulation) was also evaluated. The T (max) values were comparable, and the 90%
      confidence intervals of the geometric test/reference ratios (T/R) for
      DeltaC(SG,max), C(ss), GE, and fAUC were all within 80-125%. The parameter GE'
      was slightly outside the limits, and the parameter AUEC((0-4h)) could not be
      computed due to the presence of negative values. In acarbose BE evaluation, while
      the recommended parameter DeltaC(SG,max) is valuable, the combination of C(ss)
      and one of the newly defined glucose fluctuation parameters, GE, GE', and fAUC is
      preferable than AUEC((0-4h)). The acarbose test formulation can be initially
      considered to be bioequivalent to Glucobay(r).

PMID- 22419152
TI  - Plasma metabonomics study of rheumatoid arthritis and its Chinese medicine
      subtypes by using liquid chromatography and gas chromatography coupled with mass
      spectrometry.
AB  - Rheumatoid arthritis (RA) is the most severe type of chronic inflammatory disease
      and has always been a research hotspot in different fields. In this study, a non
      targeted metabonomics approach was carried out to profile metabolic
      characteristics of RA and its Chinese medicine subtypes by using liquid
      chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry
      (GC-MS). Plasma samples of 57 RA patients and 23 healthy controls were collected.
      On the basis of the traditional Chinese medicine (TCM), RA patients were
      classified into two main patterns, the cold pattern and the heat pattern. By
      using univariate and multivariate data analysis, we found that the RA patients
      presented diverse dysfunctions in inositol phosphate metabolism, lipid
      metabolism, amino acid metabolism, glucose metabolism, ascorbate metabolism,
      glyoxylate and dicarboxylate metabolism. The metabolic phenotypes were different
      between the RA cold pattern and the RA heat pattern. Compared with the RA cold
      pattern, the RA heat pattern showed elevated plasma concentrations of
      glycochenodeoxycholate, proline, saturated and mono-unsaturated
      phosphatidylcholine (PC) but decreased levels of urea, free fatty acid (FFA) and
      polyunsaturated PC. Our data show that metabonomics is a valuable tool in disease
      and TCM subtype research.

PMID- 22419153
TI  - Choice-specific sequences in parietal cortex during a virtual-navigation decision
      task.
AB  - The posterior parietal cortex (PPC) has an important role in many cognitive
      behaviours; however, the neural circuit dynamics underlying PPC function are not
      well understood. Here we optically imaged the spatial and temporal activity
      patterns of neuronal populations in mice performing a PPC-dependent task that
      combined a perceptual decision and memory-guided navigation in a virtual
      environment. Individual neurons had transient activation staggered relative to
      one another in time, forming a sequence of neuronal activation spanning the
      entire length of a task trial. Distinct sequences of neurons were triggered on
      trials with opposite behavioural choices and defined divergent, choice-specific
      trajectories through a state space of neuronal population activity. Cells
      participating in the different sequences and at distinct time points in the task
      were anatomically intermixed over microcircuit length scales (<100 micrometres).
      During working memory decision tasks, the PPC may therefore perform computations
      through sequence-based circuit dynamics, rather than long-lived stable states,
      implemented using anatomically intermingled microcircuits.

PMID- 22419154
TI  - Visualizing molecular juggling within a B12-dependent methyltransferase complex.
AB  - Derivatives of vitamin B(12) are used in methyl group transfer in biological
      processes as diverse as methionine synthesis in humans and CO(2) fixation in
      acetogenic bacteria. This seemingly straightforward reaction requires large,
      multimodular enzyme complexes that adopt multiple conformations to alternately
      activate, protect and perform catalysis on the reactive B(12) cofactor. Crystal
      structures determined thus far have provided structural information for only
      fragments of these complexes, inspiring speculation about the overall protein
      assembly and conformational movements inherent to activity. Here we present X-ray
      crystal structures of a complete 220 kDa complex that contains all enzymes
      responsible for B(12)-dependent methyl transfer, namely the corrinoid iron
      sulphur protein and its methyltransferase from the model acetogen Moorella
      thermoacetica. These structures provide the first three-dimensional depiction of
      all protein modules required for the activation, protection and catalytic steps
      of B(12)-dependent methyl transfer. In addition, the structures capture B(12) at
      multiple locations between its 'resting' and catalytic positions, allowing
      visualization of the dramatic protein rearrangements that enable methyl transfer
      and identification of the trajectory for B(12) movement within the large enzyme
      scaffold. The structures are also presented alongside in crystallo spectroscopic
      data, which confirm enzymatic activity within crystals and demonstrate the
      largest known conformational movements of proteins in a crystalline state. Taken
      together, this work provides a model for the molecular juggling that accompanies
      turnover and helps explain why such an elaborate protein framework is required
      for such a simple, yet biologically essential reaction.

PMID- 22419155
TI  - Collapse of polar ice sheets during the stage 11 interglacial.
AB  - Contentious observations of Pleistocene shoreline features on the tectonically
      stable islands of Bermuda and the Bahamas have suggested that sea level about
      400,000 years ago was more than 20 metres higher than it is today. Geochronologic
      and geomorphic evidence indicates that these features formed during interglacial
      marine isotope stage (MIS) 11, an unusually long interval of warmth during the
      ice age. Previous work has advanced two divergent hypotheses for these shoreline
      features: first, significant melting of the East Antarctic Ice Sheet, in addition
      to the collapse of the West Antarctic Ice Sheet and the Greenland Ice Sheet; or
      second, emplacement by a mega-tsunami during MIS 11 (ref. 4, 5). Here we show
      that the elevations of these features are corrected downwards by ~10 metres when
      we account for post-glacial crustal subsidence of these sites over the course of
      the anomalously long interglacial. On the basis of this correction, we estimate
      that eustatic sea level rose to ~6-13 m above the present-day value in the second
      half of MIS 11. This suggests that both the Greenland Ice Sheet and the West
      Antarctic Ice Sheet collapsed during the protracted warm period while changes in
      the volume of the East Antarctic Ice Sheet were relatively minor, thereby
      resolving the long-standing controversy over the stability of the East Antarctic
      Ice Sheet during MIS 11.

PMID- 22419156
TI  - Adaptive radiation of multituberculate mammals before the extinction of
      dinosaurs.
AB  - The Cretaceous-Paleogene mass extinction approximately 66 million years ago is
      conventionally thought to have been a turning point in mammalian evolution. Prior
      to that event and for the first two-thirds of their evolutionary history, mammals
      were mostly confined to roles as generalized, small-bodied, nocturnal
      insectivores, presumably under selection pressures from dinosaurs. Release from
      these pressures, by extinction of non-avian dinosaurs at the Cretaceous-Paleogene
      boundary, triggered ecological diversification of mammals. Although recent
      individual fossil discoveries have shown that some mammalian lineages diversified
      ecologically during the Mesozoic era, comprehensive ecological analyses of
      mammalian groups crossing the Cretaceous-Paleogene boundary are lacking. Such
      analyses are needed because diversification analyses of living taxa allow only
      indirect inferences of past ecosystems. Here we show that in arguably the most
      evolutionarily successful clade of Mesozoic mammals, the Multituberculata, an
      adaptive radiation began at least 20 million years before the extinction of non
      avian dinosaurs and continued across the Cretaceous-Paleogene boundary. Disparity
      in dental complexity, which relates to the range of diets, rose sharply in step
      with generic richness and disparity in body size. Moreover, maximum dental
      complexity and body size demonstrate an adaptive shift towards increased
      herbivory. This dietary expansion tracked the ecological rise of angiosperms and
      suggests that the resources that were available to multituberculates were
      relatively unaffected by the Cretaceous-Paleogene mass extinction. Taken
      together, our results indicate that mammals were able to take advantage of new
      ecological opportunities in the Mesozoic and that at least some of these
      opportunities persisted through the Cretaceous-Paleogene mass extinction. Similar
      broad-scale ecomorphological inventories of other radiations may help to
      constrain the possible causes of mass extinctions.

PMID- 22419157
TI  - Intrinsic coupling of lagging-strand synthesis to chromatin assembly.
AB  - Fifty per cent of the genome is discontinuously replicated on the lagging strand
      as Okazaki fragments. Eukaryotic Okazaki fragments remain poorly characterized
      and, because nucleosomes are rapidly deposited on nascent DNA, Okazaki fragment
      processing and nucleosome assembly potentially affect one another. Here we show
      that ligation-competent Okazaki fragments in Saccharomyces cerevisiae are sized
      according to the nucleosome repeat. Using deep sequencing, we demonstrate that
      ligation junctions preferentially occur near nucleosome midpoints rather than in
      internucleosomal linker regions. Disrupting chromatin assembly or lagging-strand
      polymerase processivity affects both the size and the distribution of Okazaki
      fragments, suggesting a role for nascent chromatin, assembled immediately after
      the passage of the replication fork, in the termination of Okazaki fragment
      synthesis. Our studies represent the first high-resolution analysis--to our
      knowledge--of eukaryotic Okazaki fragments in vivo, and reveal the
      interconnection between lagging-strand synthesis and chromatin assembly.

PMID- 22419158
TI  - Deciphering a neuronal circuit that mediates appetite.
AB  - Hypothalamic neurons that co-express agouti-related protein (AgRP), neuropeptide
      Y and gamma-aminobutyric acid (GABA) are known to promote feeding and weight gain
      by integration of various nutritional, hormonal, and neuronal signals. Ablation
      of these neurons in mice leads to cessation of feeding that is accompanied by
      activation of Fos in most regions where they project. Previous experiments have
      indicated that the ensuing starvation is due to aberrant activation of the
      parabrachial nucleus (PBN) and it could be prevented by facilitating GABA(A)
      receptor signalling in the PBN within a critical adaptation period. We speculated
      that loss of GABA signalling from AgRP-expressing neurons (AgRP neurons) within
      the PBN results in unopposed excitation of the PBN, which in turn inhibits
      feeding. However, the source of the excitatory inputs to the PBN was unknown.
      Here we show that glutamatergic neurons in the nucleus tractus solitarius (NTS)
      and caudal serotonergic neurons control the excitability of PBN neurons and
      inhibit feeding. Blockade of serotonin (5-HT(3)) receptor signalling in the NTS
      by either the chronic administration of ondansetron or the genetic inactivation
      of Tph2 in caudal serotonergic neurons that project to the NTS protects against
      starvation when AgRP neurons are ablated. Likewise, genetic inactivation of
      glutamatergic signalling by the NTS onto N-methyl D-aspartate-type glutamate
      receptors in the PBN prevents starvation. We also show that suppressing
      glutamatergic output of the PBN reinstates normal appetite after AgRP neuron
      ablation, whereas it promotes weight gain without AgRP neuron ablation. Thus we
      identify the PBN as a hub that integrates signals from several brain regions to
      bidirectionally modulate feeding and body weight.

PMID- 22419160
TI  - Virology: Influenza's tale of tails.

PMID- 22419162
TI  - Utilizing a copper MOF as a reagent in a solvent mediated reaction to form a
      topologically distinct MOF.
AB  - Employing a semi-rigid di-1,2,4-triazole ligand leads to the formation of new
      MOFs [Cu(4)(L)(4)(SO(4))(4)].4[Cu(H(2)O)(6)(SO(4))] (3) and
      [Cu(6)(L)(3)(SO(4))(5)(OH)(2)(H(2)O)(6)].13H(2)O (4). The frameworks can be
      synthesized independently, but a reaction occurs in water wherein kinetic product
      3 is used as a reagent to synthesize the topologically distinct thermodynamic
      product 4.

PMID- 22419163
TI  - Work functioning of schizophrenia patients in a rural south Indian community:
      status at 4-year follow-up.
AB  - PURPOSE: This report describes the work functioning of schizophrenia patients
      receiving antipsychotic treatment in a rural south Indian community and examines
      the factors associated with it. METHODS: We assessed work functioning of 201
      patients who have completed a minimum of 3 years of follow-up as part of a cohort
      study of schizophrenia patients receiving community-based treatment. 'Work'
      section of the Indian disability evaluation and assessment scale (IDEAS) was used
      to evaluate work-related disability at the time of recruitment and after a mean
      (SD) 47.0 (9.6) months of follow-up. Patients with moderate to profound work
      related disability were compared with those with no or mild disability across
      socio-demographic and clinical variables. RESULTS: 75 (37.3 %) were
      agriculturists; 58 (28.9 %) were pursuing household jobs; 28 (13.9 %) were daily
      wage labourers; 7 (3.5 %) were skilled labourers; 7 (3.5 %) were involved in
      other jobs. 26 (12.9 %) were not doing any sort of work. The proportion of
      patients with moderate or profound disability reduced from 137/201 (68.2 %) at
      baseline to 82/201 (40.8 %) at follow-up (p < 0.001). Work-related disability
      reduced significantly [mean (SD) work score on IDEAS was 2.2 (1.6) at baseline
      and 1.1 (1.2) at follow-up; t = -9.1; p < 0.001]. Logistic regression analysis
      showed that work-related disability was significantly associated with male
      gender, longer duration of illness, higher psychopathology and poor treatment
      adherence. CONCLUSION: Nearly two-thirds of schizophrenia patients living in this
      rural south Indian community had satisfactory work functioning, a rate, which is
      substantially higher than rates reported from high-income countries. Agrarian
      work atmosphere and rural sociocultural milieu may have contributed to this in
      our sample. However, substantial proportion of patients remains considerably
      disabled. This highlights the need for concerted, community-level efforts to
      improve their functioning.

PMID- 22419161
TI  - Suppression of the antiviral response by an influenza histone mimic.
AB  - Viral infection is commonly associated with virus-driven hijacking of host
      proteins. Here we describe a novel mechanism by which influenza virus affects
      host cells through the interaction of influenza non-structural protein 1 (NS1)
      with the infected cell epigenome. We show that the NS1 protein of influenza A
      H3N2 subtype possesses a histone-like sequence (histone mimic) that is used by
      the virus to target the human PAF1 transcription elongation complex (hPAF1C). We
      demonstrate that binding of NS1 to hPAF1C depends on the NS1 histone mimic and
      results in suppression of hPAF1C-mediated transcriptional elongation.
      Furthermore, human PAF1 has a crucial role in the antiviral response. Loss of
      hPAF1C binding by NS1 attenuates influenza infection, whereas hPAF1C deficiency
      reduces antiviral gene expression and renders cells more susceptible to viruses.
      We propose that the histone mimic in NS1 enables the influenza virus to affect
      inducible gene expression selectively, thus contributing to suppression of the
      antiviral response.

PMID- 22419164
TI  - Prediction and control of neural responses to pulsatile electrical stimulation.
AB  - This paper aims to predict and control the probability of firing of a neuron in
      response to pulsatile electrical stimulation of the type delivered by neural
      prostheses such as the cochlear implant, bionic eye or in deep brain stimulation.
      Using the cochlear implant as a model, we developed an efficient computational
      model that predicts the responses of auditory nerve fibers to electrical
      stimulation and evaluated the model's accuracy by comparing the model output with
      pooled responses from a group of guinea pig auditory nerve fibers. It was found
      that the model accurately predicted the changes in neural firing probability over
      time to constant and variable amplitude electrical pulse trains, including speech
      derived signals, delivered at rates up to 889 pulses s(-1). A simplified version
      of the model that did not incorporate adaptation was used to adaptively predict,
      within its limitations, the pulsatile electrical stimulus required to cause a
      desired response from neurons up to 250 pulses s(-1). Future stimulation
      strategies for cochlear implants and other neural prostheses may be enhanced
      using similar models that account for the way that neural responses are altered
      by previous stimulation.

PMID- 22419165
TI  - Does the influence of substituents impact upon the surface composition of
      pyrrolidinium-based ionic liquids? An angle resolved XPS study.
AB  - The surface chemistry of a series of four pyrrolidinium based ionic liquids,
      [C(n)C(1)Pyrr][Tf(2)N] where n = 4-10, is investigated by angle resolved X-ray
      photoelectron spectroscopy (ARXPS). The importance of sample purity is
      demonstrated and the stability of the ionic liquids under X-ray irradiation
      investigated. It is apparent that the surface chemistry and orientation is
      broadly analogous to that of similar imidazolium-based systems.

PMID- 22419166
TI  - Primate segmental duplication creates novel promoters for the LRRC37 gene family
      within the 17q21.31 inversion polymorphism region.
AB  - The LRRC37 gene family maps to a complex region of the human genome and has been
      subjected to multiple rounds of segmental duplication. We investigate the
      expression and regulation of this gene family in multiple tissues and organisms
      and show a testis-specific expression of this gene family in mouse but a more
      ubiquitous pattern of expression among primates. Evolutionary and phylogenetic
      analyses support a model in which new alternative promoters have been acquired
      during primate evolution. We identify two promoters, Cl8 and particularly Cl3,
      both of which are highly active in the cerebellum and fetal brain in human and
      have been duplicated from a promoter region of two unrelated genes, BPTF and
      DND1, respectively. Two of these more broadly expressed gene family members,
      LRRC37A1 and A4, define the boundary of a common human inversion polymorphism
      mapping to chromosome 17q21.31 (the MAPT locus)-a region associated with risk for
      frontal temporal dementia, Parkinsonism, and intellectual disability. We propose
      that the regulation of the LRRC37 family occurred in a stepwise manner, acquiring
      foreign promoters from BPTF and DND1 via segmental duplication. This unusual
      evolutionary trajectory altered the regulation of the LRRC37 family, leading to
      increased expression in the fetal brain and cerebellum.

PMID- 22419167
TI  - The evolution of African great ape subtelomeric heterochromatin and the fusion of
      human chromosome 2.
AB  - Chimpanzee and gorilla chromosomes differ from human chromosomes by the presence
      of large blocks of subterminal heterochromatin thought to be composed primarily
      of arrays of tandem satellite sequence. We explore their sequence composition and
      organization and show a complex organization composed of specific sets of
      segmental duplications that have hyperexpanded in concert with the formation of
      subterminal satellites. These regions are highly copy number polymorphic between
      and within species, and copy number differences involving hundreds of copies can
      be accurately estimated by assaying read-depth of next-generation sequencing data
      sets. Phylogenetic and comparative genomic analyses suggest that the structures
      have arisen largely independently in the two lineages with the exception of a few
      seed sequences present in the common ancestor of humans and African apes. We
      propose a model where an ancestral human-chimpanzee pericentric inversion and the
      ancestral chromosome 2 fusion both predisposed and protected the chimpanzee and
      human genomes, respectively, to the formation of subtelomeric heterochromatin.
      Our findings highlight the complex interplay between duplicated sequences and
      chromosomal rearrangements that rapidly alter the cytogenetic landscape in a
      short period of evolutionary time.

PMID- 22419168
TI  - Evaluation of hygiene practices and microbiological status of ready-to-eat
      vegetable salads in Spanish school canteens.
AB  - BACKGROUND: This study was conducted in eight Spanish school canteens during the
      period 2008-2009. Food handlers' practices, kitchen equipment, hygiene/sanitation
      conditions and handling practices were evaluated using checklists. In parallel,
      the microbiological quality and safety of ready-to-eat (RTE) vegetable salads
      were assessed. In addition, food contact surfaces and environmental air quality
      of different areas were analysed. The study determined the relationship between
      the microbiological quality of RTE foods and food handling practices, together
      with the degree of contamination of working surfaces and environmental
      contamination of processing and distribution areas. RESULTS: Some deficiencies
      were found regarding the use and change of gloves, hand-washing and cleanliness
      of working surfaces. The microbial levels detected in the foods examined
      indicated the absence of pathogens in the samples analysed. Surface counts were
      higher on cutting boards and faucets, showing insufficient cleanliness
      procedures. CONCLUSION: This study constitutes a descriptive analysis of the
      hygiene/sanitation conditions implemented in food service systems in eight
      Spanish school canteens. The results should help risk managers to better define
      control measures to be adopted in order to prevent foodborne infections.

PMID- 22419169
TI  - Neonatal progeria: increased ratio of progerin to lamin A leads to progeria of
      the newborn.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is an important model disease for
      premature ageing. Affected children appear healthy at birth, but develop the
      first symptoms during their first year of life. They die at an average age of 13
      years, mostly because of myocardial infarction or stroke. Classical progeria is
      caused by the heterozygous point mutation c.1824C>T in the LMNA gene, which
      activates a cryptic splice site. The affected protein cannot be processed
      correctly to mature lamin A, but is modified into a farnesylated protein
      truncated by 50 amino acids (progerin). Three more variations in LMNA result in
      the same mutant protein, but different grades of disease severity. We describe a
      patient with the heterozygous LMNA mutation c.1821G>A, leading to neonatal
      progeria with death in the first year of life. Intracellular lamin A was
      downregulated in the patient's fibroblasts and the ratio of progerin to lamin A
      was increased when compared with HGPS. It is suggestive that the ratio of
      farnesylated protein to mature lamin A determines the disease severity in
      progeria.

PMID- 22419170
TI  - A genome-wide search for linkage to allergic rhinitis in Danish sib-pair
      families.
AB  - Allergic rhinitis (AR) is a complex disorder with a polygenic, multifactorial
      aetiology. Twin studies have found the genetic contribution to be substantial. We
      collected and clinically characterised a sample consisting of 127 Danish nuclear
      families with at least two siblings suffering from AR or allergic conjunctivitis
      including 540 individuals (286 children and 254 parents). A whole-genome linkage
      scan, using 424 microsatellite markers, was performed on both this sample and an
      earlier collected sample consisting of 130 families with atopic dermatitis and
      other atopic disorders. A third sib-pair family sample, which was previously
      collected and genotyped, was added to the analysis increasing the total sample
      size to 357 families consisting of 1508 individuals. In total, 190 families with
      AR was included. The linkage analysis software Genehunter NPL, Genehunter MOD,
      and Genehunter Imprinting were used to obtain nonparametric and parametric
      linkage results. Family-based association analysis of positional candidate SNPs
      was carried out using the FBAT program. We obtained genome-wide significant
      linkage to a novel AR locus at 1p13 and suggestive linkage to two novel regions
      at 1q31-q32 and 20p12, respectively. Family-based association analysis of SNPs in
      the candidate locus DNND1B/CRB1 at 1q31 showed no significant association and
      could not explain the linkage signal observed. Suggestive evidence of linkage was
      also obtained at three AR loci previously reported (2q14-q23, 2q23, and 12p13)
      and indication of linkage was observed at a number of additional loci. Likely
      maternal imprinting was observed at 2q23, and possible maternal imprinting at
      3q28.

PMID- 22419171
TI  - A family-based association test to detect gene-gene interactions in the presence
      of linkage.
AB  - For many complex diseases, quantitative traits contain more information than
      dichotomous traits. One of the approaches used to analyse these traits in family
      based association studies is the quantitative transmission disequilibrium test
      (QTDT). The QTDT is a regression-based approach that models simultaneously
      linkage and association. It splits up the association effect in a between- and a
      within-family genetic component to adjust and test for population stratification
      and includes a variance components method to model linkage. We extend this
      approach to detect gene-gene interactions between two unlinked QTLs by adjusting
      the definition of the between- and within-family component and the variance
      components included in the model. We simulate data to investigate the influence
      of the epistasis model, linkage disequilibrium patterns between the markers and
      the QTLs, and allele frequencies on the power and type I error rates of the
      approach. Results show that for some of the investigated settings, power gains
      are obtained in comparison with FAM-MDR. We conclude that our approach shows
      promising results for candidate-gene studies where too few markers are available
      to correct for population stratification using standard methods (for example
      EIGENSTRAT). The proposed method is applied to real-life data on hypertension
      from the FLEMENGHO study.

PMID- 22419172
TI  - Promoter alteration causes transcriptional repression of the POMGNT1 gene in limb
      girdle muscular dystrophy type 2O.
AB  - Limb-girdle muscular dystrophy type 2O (LGMD2O) belongs to a group of rare
      muscular dystrophies named dystroglycanopathies, which are characterized
      molecularly by hypoglycosylation of alpha-dystroglycan (alpha-DG). Here, we
      describe the first dystroglycanopathy patient carrying an alteration in the
      promoter region of the POMGNT1 gene (protein O-mannose beta-1,2-N
      acetylglucosaminyltransferase 1), which involves a homozygous 9-bp duplication (
      83_-75dup). Analysis of the downstream effects of this mutation revealed a
      decrease in the expression of POMGNT1 mRNA and protein because of negative
      regulation of the POMGNT1 promoter by the transcription factor ZNF202 (zinc
      finger protein 202). By functional analysis of various luciferase constructs, we
      localized a proximal POMGNT1 promoter and we found a 75% decrease in luciferase
      activity in the mutant construct when compared with the wild type.
      Electrophoretic mobility shift assay (EMSA) revealed binding sites for the Sp1,
      Ets1 and GATA transcription factors. Surprisingly, the mutation generated an
      additional ZNF202 binding site and this transcriptional repressor bound strongly
      to the mutant promoter while failing to recognize the wild-type promoter.
      Although the genetic causes of dystroglycanopathies are highly variable, they
      account for only 50% of the cases described. Our results emphasize the importance
      of extending the mutational screening outside the gene-coding region in
      dystroglycanopathy patients of unknown aetiology, because mutations in noncoding
      regions may be the cause of disease. Our findings also underline the requirement
      to perform functional studies that may assist the interpretation of the
      pathogenic potential of promoter alterations.

PMID- 22419173
TI  - Somatic cell reprogramming for regenerative medicine: SCNT vs. iPS cells.
AB  - Reprogramming of somatic cells to a pluripotent state holds huge potentials for
      regenerative medicine. However, a debate over which method is better, somatic
      cell nuclear transfer (SCNT) or induced pluripotent stem (iPS) cells, still
      persists. Both approaches have the potential to generate patient-specific
      pluripotent stem cells for replacement therapy. Yet, although SCNT has been
      successfully applied in various vertebrates, no human pluripotent stem cells have
      been generated by SCNT due to technical, legal and ethical difficulties. On the
      other hand, human iPS cell lines have been reported from both healthy and
      diseased individuals. A recent study reported the generation of triploid human
      pluripotent stem cells by transferring somatic nuclei into oocytes, a variant
      form of SCNT. In this essay, we discuss this progress and the potentials of these
      two reprogramming approaches for regenerative medicine.

PMID- 22419174
TI  - Effects of exogenous hydrogen sulphide on calcium signalling, background (TASK) K
      channel activity and mitochondrial function in chemoreceptor cells.
AB  - It has been proposed that endogenous H(2)S mediates oxygen sensing in
      chemoreceptors; this study investigates the mechanisms by which H(2)S excites
      carotid body type 1 cells. H(2)S caused a rapid reversible increase in
      intracellular calcium with EC(50) ~ 6 MUM. This [Ca(2+)](i) response was
      abolished in Ca-free Tyrode. In perforated patch current clamp recordings, H(2)S
      depolarised type 1 cells from -59 to -35 mV; this was accompanied by a robust
      increase in [Ca(2+)](i). Voltage clamping at the resting membrane potential
      abolished the H(2)S-induced rise in [Ca(2+)](i). H(2)S inhibited background K(+)
      current in whole cell perforated patch and reduced background K(+) channel
      activity in cell-attached patch recordings. It is concluded that H(2)S excites
      type 1 cells through the inhibition of background (TASK) potassium channels
      leading to membrane depolarisation and voltage-gated Ca(2+) entry. These effects
      mimic those of hypoxia. H(2)S also inhibited mitochondrial function over a
      similar concentration range as assessed by NADH autofluorescence and measurement
      of intracellular magnesium (an index of decline in MgATP). Cyanide inhibited
      background K channels to a similar extent to H(2)S and prevented H(2)S exerting
      any further influence over channel activity. These data indicate that the effects
      of H(2)S on background K channels are a consequence of inhibition of oxidative
      phosphorylation. Whilst this does not preclude a role for endogenous H(2)S in
      oxygen sensing via the inhibition of cytochrome oxidase, the levels of H(2)S
      required raise questions as to the viability of such a mechanism.

PMID- 22419175
TI  - Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger
      isoform 3 in response to chronic metabolic and respiratory acidosis.
AB  - The Na(+/)H(+) exchanger isoform 3 (NHE3) is essential for HCO(3)(-) reabsorption
      in renal proximal tubules. The expression and function of NHE3 must adapt to acid
      base conditions. The goal of this study was to elucidate the mechanisms
      responsible for higher proton secretion in proximal tubules during acidosis and
      to evaluate whether there are differences between metabolic and respiratory
      acidosis with regard to NHE3 modulation and, if so, to identify the relevant
      parameters that may trigger these distinct adaptive responses. We achieved
      metabolic acidosis by lowering HCO(3)(-) concentration in the cell culture medium
      and respiratory acidosis by increasing CO(2) tension in the incubator chamber. We
      found that cell-surface NHE3 expression was increased in response to both forms
      of acidosis. Mild (pH 7.21 +/- 0.02) and severe (6.95 +/- 0.07) metabolic
      acidosis increased mRNA levels, at least in part due to up-regulation of
      transcription, whilst mild (7.11 +/- 0.03) and severe (6.86 +/- 0.01) respiratory
      acidosis did not up-regulate NHE3 expression. Analyses of the Nhe3 promoter
      region suggested that the regulatory elements sensitive to metabolic acidosis are
      located between -466 and -153 bp, where two consensus binding sites for SP1, a
      transcription factor up-regulated in metabolic acidosis, were localised. We
      conclude that metabolic acidosis induces Nhe3 promoter activation, which results
      in higher mRNA and total protein level. At the plasma membrane surface, NHE3
      expression was increased in metabolic and respiratory acidosis alike, suggesting
      that low pH is responsible for NHE3 displacement to the cell surface.

PMID- 22419176
TI  - The evolution of personalized cancer genetic counseling in the era of
      personalized medicine.
AB  - Practice changes in cancer genetic counseling have occurred to meet the demand
      for cancer genetic services. As cancer genetics continues to impact not only
      prevention strategies but also treatment decisions, current cancer genetic
      counseling models will need to be tailored to accommodate emerging clinical
      indications. These clinical indications include: surgical prophylactic bilateral
      mastectomy candidates, PARP-inhibitor candidates, patients with abnormal tumor
      screening results for Lynch syndrome, and post-test counseling patients (after
      genetic testing is ordered by another healthcare provider). A more personalized,
      multidisciplinary approach to selecting the best framework, for a given clinical
      indication, may become increasingly necessary in this era of personalized
      medicine.

PMID- 22419177
TI  - High level population differentiation of finless porpoises (Neophocaena
      phocaenoides) in Chinese waters revealed by sequence variability of four nuclear
      introns.
AB  - In the present study, sequence variations at four nuclear introns which were
      respectively from the parathyroid hormone-like (PTH) gene, isolate Pdalz1692
      interferon (IFN) gene, peripherin-like (RDS) gene, and tyrosine kinase receptor
      like (KIT) gene, were examined to analyze genetic diversity and population
      structure of the finless porpoise (Neophocaena phocaenoides) in Chinese waters.
      High among-population differentiation was revealed, with a significant genetic
      structure between populations (PTH: F(ST) = 0.29, P < 0.001; IFN1@: F(ST) = 0.23,
      P < 0.001; RDS: F(ST) = 0.12, P < 0.001; KIT: F(ST) = 0.16, P < 0.001) shown by
      the analysis of molecular variance. Although common haplotypes accounted for more
      than one half of all samples examined, many haplotypes were found to be
      population-specific. The Tajima's D, Fu's tests and mismatch distributions all
      suggested a recent colonization and population expansion of finless porpoises in
      Chinese waters. In view of special reference to the conservation priority of the
      Yangtze finless porpoises, special protection measures must be taken urgently for
      this population.

PMID- 22419178
TI  - Testing convergent and parallel adaptations in talpids humeral mechanical
      performance by means of geometric morphometrics and finite element analysis.
AB  - The shape and mechanical performance in Talpidae humeri were studied by means of
      Geometric Morphometrics and Finite Element Analysis, including both extinct and
      extant taxa. The aim of this study was to test whether the ability to dig,
      quantified by humerus mechanical performance, was characterized by convergent or
      parallel adaptations in different clades of complex tunnel digger within
      Talpidae, that is, Talpinae+Condylura (monophyletic) and some complex tunnel
      diggers not belonging to this clade. Our results suggest that the pattern
      underlying Talpidae humerus evolution is evolutionary parallelism. However, this
      insight changed to true convergence when we tested an alternative phylogeny based
      on molecular data, with Condylura moved to a more basal phylogenetic position.
      Shape and performance analyses, as well as specific comparative methods, provided
      strong evidence that the ability to dig complex tunnels reached a functional
      optimum in distantly related taxa. This was also confirmed by the lower
      phenotypic variance in complex tunnel digger taxa, compared to non-complex tunnel
      diggers. Evolutionary rates of phenotypic change showed a smooth deceleration in
      correspondence with the most recent common ancestor of the Talpinae+Condylura
      clade.

PMID- 22419179
TI  - Optimal radiotherapy for non-small-cell lung cancer: current progress and future
      challenges.
AB  - Radiotherapy has a key role in treating lung cancer. Advances in physics and
      computer technology have improved radiation delivery systems. With innovations in
      the radiation therapy of non-small-cell lung cancer (NSCLC), new strategies have
      emerged, such as intensity-modulated radiation therapy, stereotactic body
      radiation therapy, and particle therapy. Compared with previous methods, these
      newer technologies can deliver even higher doses precisely to the tumor while
      minimizing doses to normal tissues, which should lead to better tumor control
      with less toxicity. In patients with stage I NSCLC, stereotactic body radiation
      therapy is highly effective and may achieve local control and survival equivalent
      to that achieved with surgery. In patients with stage III NSCLC, dose escalation
      has been investigated using three-dimensional conformal radiation therapy,
      intensity-modulated radiation therapy, and particle therapy. The results from
      ongoing randomized trials on both patient populations are awaited. It is
      important to generate new hypotheses and to explore newer radiotherapy approaches
      to overcome NSCLC.

PMID- 22419180
TI  - Risk-adjusted and case-matched comparative study between antegrade and retrograde
      cerebral perfusion during aortic arch surgery: based on the Japan Adult
      Cardiovascular Surgery Database : the Japan Cardiovascular Surgery Database
      Organization.
AB  - PURPOSE: Antegrade cerebral perfusion (ACP) and retrograde cerebral perfusion
      (RCP) are two major types of brain protection for aortic arch surgery. A large
      scale clinical study of RCP and ACP is important to clarify the respective
      characteristics for major adverse events. We conducted a comparative study to
      evaluate up-to-date clinical outcomes in Japan based on the Japan Adult
      Cardiovascular Surgery Database (JACVSD). METHODS: The subjects were confined to
      cases undergone electively with ACP or RCP for nondissection aneurysms in the
      ascending aorta and aortic arch between 2005 and 2008 from 13 467 aortic
      surgeries. There were 2209 ACP cases and 583 RCP cases. A risk-adjusted
      comparison based on 30-day mortality, operative mortality, and major morbidity
      was assessed by a multivariable logistic regression analysis. A conditional
      logistic regression analysis was also conducted in 499 propensity matched-pairs
      with ACP and RCP. RESULTS: A risk-adjusted analysis showed no significant
      differences between the ACP and RCP groups regarding 30-day mortality (3.5% vs.
      2.6%), operative mortality (5.3% vs. 4.1%), or stroke (6.8% vs. 3.1%). Propensity
      matched pairs also revealed no significant differences between ACP and RCP
      regarding 30-day mortality (3.4% vs. 2.4%), operative mortality (3.8% vs. 3.4%),
      or stroke rate (5.0% vs. 3.0%); however, RCP resulted in a significantly higher
      rate of transient neurological dysfunction (3.0% vs. 5.8%) and need for dialysis
      (1.6% vs. 4.2%). CONCLUSION: Both RCP and ACP provide comparable clinical
      outcomes regarding both the mortality and stroke rates. RCP resulted in a higher
      incidence only in patients demonstrating transient neurological dysfunction and
      the need for dialysis.

PMID- 22419181
TI  - Experimental study on effective application of fibrin glue.
AB  - PURPOSE: Fibrin glue is effective for maintaining hemostasis after anastomosis
      and for filling needle holes after cardiothoracic and vascular surgery, but few
      experimental studies concerning methods of application to obtain more effective
      hemostasis have been reported. METHODS: Bolheal was used as the fibrin glue.
      Fibrinogen solution (A, 0.3 ml) and thrombin solution (B, 0.3 ml), components of
      fibrin glue, were applied to the needle holes by the following four methods:
      group 1 (n = 8), drip method; group 2 (n = 8), spray method; group 3 (n = 8), rub
      and-spray method; group 4 (n = 8), rub-andrub method. Additional studies were
      done in groups 3 and 4 to evaluate the hemostatic effect with different curing
      times and temperatures. RESULTS: The pressure at which the fibrin sealant
      ruptured were significantly higher in group 3 (109 +/- 16 mmHg) and group 4 (113
      +/- 7) (for both groups: P < 0.05 vs. group 1 (22 +/- 8) and group 2 (64 +/-
      10)). The pressure increased with prolongation of the curing time, and
      significant differences were noted between the pressures at >= 2 min and that at
      30 s (both groups: P < 0.05 vs. 30 s). The curing temperature had no significant
      influence in the two groups. Microscopically, the glue effectively plugged the
      needle holes in groups 3 and 4. CONCLUSION: Compared with the current drip and
      spray methods, more effective hemostasis was obtained by rubbing on the fibrin
      glue.

PMID- 22419182
TI  - Transthoracic repair of an incarcerated diaphragmatic hernia using hexamethylene
      diisocyanate cross-linked porcine dermal collagen (Permacol).
AB  - It is the general surgeon who commonly repairs paraesophageal hernias nowadays,
      and they are repaired laparoscopically, making the performance of thoracotomy
      relatively rare. Whether to use prosthetic materials to repair the hiatus is
      still under debate, as is the question of which material to use, if any. We
      report a case of a 38-year-old man who had a large, incarcerated paraesophageal
      hernia. He had a past history of extensive abdominal surgery for exomphalos,
      which rendered any abdominal surgical approach a high-risk procedure. We
      therefore decided to proceed with thoracotomy and repair of the hiatus with
      hexamethylene diisocyanate (HMDI) cross-linked porcine dermal collagen. He made a
      good recovery with no complications.

PMID- 22419183
TI  - Esophageal cancer with racemose hemangioma of the bronchial arteries.
AB  - We report a case of esophageal cancer in a patient with a racemose hemangioma of
      the bronchial arteries. A 76-year-old man was admitted to the hospital with
      unexplained weight loss. Endoscopic examination revealed enhancing vessels in the
      upper to middle esophageal wall and a type 3 tumor in the lower esophagus. He
      underwent neoadjuvant chemotherapy with cisplatin and 5-fluorouracil and
      underwent a lower esophageal resection through a left thoracoabdominal incision.
      He was free from hemoptysis and had no recurrence of esophageal cancer for 1 year
      following the procedure. This case is not only rare, it supports the decision to
      perform an operative procedure.

PMID- 22419184
TI  - Successful one-stage surgical removal of intravenous leiomyomatosis with cardiac
      extension in an elderly patient.
AB  - Intravenous leiomyomatosis is a benign smooth muscle tumor that sometimes spreads
      to the right heart via the inferior vena cava. A complete surgical resection is
      necessary to ensure its successful treatment. Surgical removal has been performed
      safely in middle-aged patients. Here we report a case of successful surgical
      removal in an elderly woman (age 81 years). The woman was admitted with
      palpitation and diagnosed as having an intravenous leiomyomatosis with cardiac
      extension. She underwent a one-stage surgical removal with cardiopulmonary bypass
      and circulatory arrest. We therefore recommend a one-stage operation, if
      possible, even in elderly patients.

PMID- 22419185
TI  - Aorto-pseudoaneurysm-ventricular regurgitation after aortic root replacement.
AB  - We describe a 48-year-old man with aorto-pseudoaneurysm-ventricular
      regurgitation. It was due to disruption of both proximal and distal anastomoses
      after aortic root replacement for detachment of a prosthetic valve implanted for
      a sinus of Valsalva aneurysm with aortic valve regurgitation. The chest was
      opened during cardiopulmonary bypass using a deep hypothermic circulatory arrest
      to avoid rupture of the aneurysm because of a close relation between the
      pseudoaneurysm and the sternum. Aortic root re-replacement was performed
      successfully.

PMID- 22419186
TI  - Surgical correction of tetralogy of Fallot in a 61-year-old patient.
AB  - Tetralogy of Fallot (TOF) is a congenital heart disease that is usually diagnosed
      and treated during infancy. Only 3% of such patients reach the age of 40 without
      surgery. We describe a 61-year-old woman with uncorrected TOF that was
      successfully treated by radical surgery. The patient presented with exertional
      dyspnea, insomnia, and malaise. Echocardiography and cardiac catheterization
      indicated a dilated, severely hypertrophic right ventricle, ventricular septal
      defect, an overriding aorta, and infundibular stenosis in the right ventricular
      outflow tract. All symptoms disappeared after full surgical correction, which
      remains the preferred treatment for adult TOF because it confers long-term
      survival and an improved quality of life.

PMID- 22419187
TI  - Pulmonary lymphoepithelioma-like carcinoma with rapid progression.
AB  - Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare entity, commonly
      associated in East Asia with Epstein-Barr virus (EBV) infection. A 71-year-old
      woman underwent partial resection of the left lower lobe for a 17-mm nodule and
      was subsequently diagnosed with pulmonary LELC. Six months postoperatively, chest
      computed tomography (CT) showed lymphadenopathy in the left hilum and a 16-mm
      nodule in the S6 segment of the left lower lobe that had been difficult to point
      out (3 mm in size) at the initial surgery. She underwent a second surgical
      resection because of rapid progression-a clinical course at variance with the
      generally good prognosis for pulmonary LELC. At admission, the EBV
      deoxyribonucleic acid (DNA) blood level was 40 copies/MUg. The EBV DNA was
      undetectable after the second surgery.

PMID- 22419188
TI  - Thoracoscopic resection with intraoperative use of methylene blue to localize
      mediastinal parathyroid adenomas.
AB  - We report a case of thoracoscopic resection of mediastinal parathyroid adenomas
      using methylene blue to localize the tumors during the operation. After methylene
      blue 4 mg/kg was injected intravenously, we easily identified methylene blue
      stained parathyroid glands and successfully resected them with sufficient
      surgical margins. The use of methylene blue for detection of parathyroid adenoma
      is a useful technique.

PMID- 22419189
TI  - Surgical management of primary intrathoracic goiters.
AB  - Intrathoracic goiters account for 3.1%-5.8% of all mediastinal masses. Primary
      intrathoracic goiters, which receive their blood supply from mediastinal vessels
      and disconnect at the cervical thyroid, are even rarer. This report presents two
      cases of surgical resection of benign and malignant primary intrathoracic
      goiters. Usefulness of a whole-body (18)F-fluorine-2-fluoro-D: -glucose positron
      emission tomography/computed tomography study and intraoperative fine-needle
      aspiration cytology in the management of primary intrathoracic goiters is
      discussed.

PMID- 22419190
TI  - Intrapulmonary neurofibroma independent of neurofibromatosis type 1.
AB  - Intrapulmonary neurofibromas without neurofibromatosis type 1 are rare-so rare
      that only 11 cases have been reported previously. This case report describes a 37
      year-old woman who was otherwise healthy. Chest radiography and computed
      tomography showed a solitary nodule, 20 mm diameter, in the left lung. The tumor
      was removed and examined. It was not encapsulated but was covered with an intact
      bronchial mucosa and lacked a clear partition into two areas of Antoni A (a
      palisading cellular component) and Antoni B (a loose myxoid component). Tumor
      cells were strongly positive for neuron-specific enolase and S-100 protein. These
      data characterized the tumor as a rare benign neurofibroma. The patient shows no
      sign of recurrence after 12 months of follow-up. We reviewed and characterized
      surgically resected cases of intrapulmonary neurofibroma without
      neurofibromatosis type 1 especially in comparison with cases of
      endotracheobronchial neurofibroma.

PMID- 22419191
TI  - Recurrent rupture of intercostal artery aneurysms in neurofibromatosis type 1.
AB  - Vasculopathy associated with neurofibromatosis type 1 (NF-1) can cause a
      spontaneous hemothorax, which is an uncommon but life-threatening complication of
      the disease. We report a case of recurrent rupture of intercostal artery
      aneurysms in an NF-1 patient. A 40-year-old man with NF-1 suffered from a right
      spontaneous hemothorax. The bleeding source was not identified by dynamic
      contrast-enhanced computed tomography (CT), so he was initially treated by
      conservative therapy. However, repeated contrast CT revealed aneurysms of the
      right 10th intercostal artery. They were successfully occluded by transcatheter
      arterial embolization (TAE). Seven months afterward, he presented with sudden
      lower back pain and was diagnosed with a contralateral spontaneous hemothorax due
      to a ruptured aneurysm of the left 12th intercostal artery. TAE was successfully
      performed.

PMID- 22419192
TI  - First experience of robotic extended thymectomy in Japan for myasthenia gravis
      with thymoma.
AB  - We performed robot (da Vinci)-assisted thoracoscopic extended thymectomy (rThx)
      for myasthenia gravis with thymoma. The patient was a 66-year-old woman who
      complained of palpebral heaviness. Robotic operation was performed in the supine
      position by placing four ports in the right chest wall under 10 mmHg CO(2)
      insufflation using three arms and one assist port. Compared with conventional
      video-assisted thoracic surgery (VATS), the bilateral upper horns, fat around the
      diaphragm, and aortopulmonary window could be resected more easily. The tumor
      measured 41 mm maximum diameter and was diagnosed as type AB noninvasive thymoma.
      The operating time was 298 min, console operating time was 203 min, and the
      amount of bleeding was small. The postoperative course was uneventful with no
      complications. This is a report of the first Japanese case of rThx for myasthenia
      gravis. rThx is a promising technique, and further improvement in the procedure
      is expected.

PMID- 22419193
TI  - Surgical removal of a migrated duct occluder device from the right pulmonary
      artery without cardiopulmonary bypass.
AB  - As the use of percutaneous intervention is increasing for closure of the patent
      ductus arteriosus, procedure-related complications are also on the rise. An
      Amplatzer duct occluder used in a 4-year-old child was dislodged into the right
      pulmonary artery. It was removed through median sternotomy by temporarily
      occluding the right pulmonary artery.

PMID- 22419195
TI  - Perceptual pseudoneglect in schizophrenia: candidate endophenotype and the role
      of the right parietal cortex.
AB  - Several contributions have reported an altered expression of pseudoneglect in
      psychiatric disorders, highlighting the existence of an anomalous brain
      lateralization in affected subjects. Surprisingly, no studies have yet
      investigated pseudoneglect in first-degree relatives (FdR) of psychiatric
      patients. We investigated performance on "paper and pencil" line bisection (LB)
      tasks in 68 schizophrenic patients (SCZ), 42 unaffected FdR, 41 unipolar
      depressive patients (UP), and 103 healthy subjects (HS). A subgroup of 20 SCZ and
      16 HS underwent computerized LB and mental number line bisection (MNL) tasks
      requiring judgment of prebisected lines and numerical intervals. Moreover, we
      evaluated, in a subgroup of 15 SCZ, performance on LB and MNL before and after
      parietal transcranial direct current stimulation (tDCS). In comparison to HS and
      UP, SCZ showed a systematic rightward bias on LB, partially corrected by
      selective right posterior parietal tDCS. Interestingly, even FdR showed a lack of
      pseudoneglect on LB, expressing a mean error lying in the middle between those of
      HS and SCZ. On the other hand, our results showed no significant difference
      between the performance of SCZ and HS on MNL. Both groups showed a comparable
      leftward bias that could not be significantly altered after left or right
      parietal tDCS. These findings confirm the existence of reduced lateralization in
      SCZ, suggesting specific impaired functioning of the right parietal lobule.
      Notably, we report a lack of pseudoneglect not only in SCZ but also in FdR,
      raising the hypothesis that an inverted laterality pattern may be considered a
      concrete marker of schizotypal traits.

PMID- 22419196
TI  - Heart rate variability dynamics during low-dose propofol and dexmedetomidine
      anesthesia.
AB  - Heart rate variability (HRV) has been observed to decrease during anesthesia, but
      changes in HRV during loss and recovery of consciousness have not been studied in
      detail. In this study, HRV dynamics during low-dose propofol (N = 10) and
      dexmedetomidine (N = 9) anesthesia were estimated by using time-varying methods.
      Standard time-domain and frequency-domain measures of HRV were included in the
      analysis. Frequency-domain parameters like low frequency (LF) and high frequency
      (HF) component powers were extracted from time-varying spectrum estimates
      obtained with a Kalman smoother algorithm. The Kalman smoother is a parametric
      spectrum estimation approach based on time-varying autoregressive (AR) modeling.
      Prior to loss of consciousness, an increase in HF component power indicating
      increase in vagal control of heart rate (HR) was observed for both anesthetics.
      The relative increase of vagal control over sympathetic control of HR was overall
      larger for dexmedetomidine which is in line with the known sympatholytic effect
      of this anesthetic. Even though the inter-individual variability in the HRV
      parameters was substantial, the results suggest the usefulness of HRV analysis in
      monitoring dexmedetomidine anesthesia.

PMID- 22419197
TI  - Detection of creatine in rat muscle by FTIR spectroscopy.
AB  - There is a current lack of clarity regarding the use of Fourier-transform
      infrared spectroscopy (FT-IR) to evaluate intramuscular concentrations of
      creatine (Cr). Thus, the aim of this study was to assess the FT-IR spectral
      features of tibialis anterior muscle in rats submitted in conditions that were
      expected to perturb the Cr pool. First, an experiment was performed to ensure
      that FT-IR was able to detect the Cr intramuscular in sedentary and supplemented
      rats (Experiment 1). The effect of physical exercise on spectral muscle features
      was then examined, especially in relation to the spectroscopy markers (Experiment
      2). Using pure Cr (control), it was possible to verify that only the peaks
      centered at 1308 and 1396 cm(-1) of all the spectra showed the same peak
      positions, indicating these FT-IR shifts as indirect markers of Cr intramuscular
      content. Experiment 2 revealed a higher Cr content for the Cr-supplemented and
      exercised animals than the rats of other groups. In conclusion, it was
      demonstrated that FT-IR spectroscopy using 1396 cm(-1) and mainly 1308 band was
      able to monitor Cr muscle content in rats sedentary, Cr-supplemented, and
      submitted to physical training. Besides, FT-IR could be a feasible method for the
      nondestructive assessment of Cr skeletal muscle content.

PMID- 22419198
TI  - Vitamin d status and indices of bone turnover in older European adults.
AB  - An increased rate of bone turnover increases risk of osteoporotic fracture later
      in life. The concentration of 25-hydroxyvitamin D that contributes to an elevated
      rate of bone turnover in older adults is unclear. The objective of this study was
      to investigate the associations between 25-hydroxyvitamin D and biochemical
      markers of bone turnover in an older, pan-European cohort. 25-hydroxyvitamin D
      and serum markers of bone-formation (osteocalcin and bone-specific alkaline
      phosphatase) were assessed by ELISA, while urinary markers of bone-resorption
      (pyridinoline and deoxypyridinoline) were assessed by HPLC. Six percent, 36 %,
      and 64 % of subjects had 25-hydroxyvitamin D concentrations < 25, < 50, and < 80
      nmol/L throughout the year, respectively. 25-hydroxyvitamin D was significantly
      and inversely correlated with serum bone-specific alkaline phosphatase (r =
      0.119; p = 0.022) and urinary pyridinoline (r = 0.207; p < 0.0001) and
      deoxypyridinoline (r = 0.230; p < 0.0001). Stratification on the basis of
      tertiles [T] of 25-hydroxyvitamin D (< 47.6 [T(1)]; 47.6 - 85.8 [T2]; > 85.8 [T3]
      nmol/L), showed that urinary pyridinoline and deoxypyridinoline were
      significantly lower in subjects in the 2(nd) and 3(rd) compared to the 1(st)
      tertile (p < 0.015). Low vitamin D status (< 50 nmol/L) was associated with an
      increased rate of bone turnover in this older pan-European cohort.

PMID- 22419199
TI  - Effect of buckwheat sprouts and groats on the antioxidant potential of blood and
      caecal parameters in rats.
AB  - The aim of this study was to investigate whether dietary buckwheat sprouts,
      cultivated without or with light exposure, exerted different effects on the lower
      gut, antioxidant status, and lipoprotein profile in rats. For 4 weeks, rats were
      given a diet containing 30 % expanded buckwheat seeds or 5 % buckwheat sprouts,
      cultivated with or without light exposure. Buckwheat sprouts that were cultivated
      under light and dark conditions, and expanded seeds, differed in the levels of
      total phenolic compounds and Trolox Equivalent Antioxidant Capacity values. All
      buckwheat products added to the diets decreased pH value and dry matter
      concentration in the caecal digesta compared with the control group. As compared
      to the control group, the addition of buckwheat products caused a higher
      glycolytic activity and the production of short-chain fatty acids in the caecum
      of the rats. There were no significant differences in the plasma concentrations
      of glucose, total cholesterol, nor triglycerides between the groups. The
      concentration of high-density lipoprotein (HDL)-cholesterol was significantly
      higher, and the atherogenic index of plasma was lower in rats administered
      buckwheat sprouts cultivated in the light, compared to the group fed sprouts
      cultivated in the dark. Total plasma antioxidant status, activity of glutathione
      peroxidase, and superoxide dismutase in whole blood were not affected by dietary
      treatment. Results of the experiment indicated enhanced benefits of dietary
      supplementation with buckwheat sprouts cultivated under light, especially in
      relation to the serum lipoprotein profile.

PMID- 22419200
TI  - Effects on vitamin A deficiency in children of periodic high-dose supplements and
      of fortified oil promotion in a deficient area of the Philippines.
AB  - Regular semi-annual distribution of high-dose (200,000 IU) vitamin A capsules
      (VACs) to children 1 - 5 years of age (previously identified as underweight), in
      Leyte Province, the Philippines, was compared to providing extra VACs to give
      three-monthly dosing, and to vitamin A-fortified cooking oil (VAFO) promotion
      (with continued VACs every 6 months). Serum retinol (SR) was measured at baseline
      and after 12 or 18 months (for VAFO). No sustained increase in SR was determined
      from the three-month VAC dosing regimen, and the prevalence of vitamin A
      deficiency (VAD) as assessed by SR (< 20 mcg / dL) remained around 30 % (in line
      with national survey estimates over the previous 15 years). The major difference
      found was that 18 months of VAFO (of which 9 months had sustained promotion) was
      associated with reducing the prevalence of VAD to < 10 %. The effective
      fortification and lack of effect of semi-annual VAC results are in line with
      previous studies; testing with dosing of VAC every three months is a new
      intervention. The results imply that promotion of fortified oil would reduce VAD
      in these conditions; whether it can replace or needs to be added to semi-annual
      VAC dosing remains to be determined. A phased changeover to reliance on fortified
      commodities (including oil) with careful monitoring of VAD trends is indicated.

PMID- 22419201
TI  - Marked gender difference in plasma total homocysteine concentrations in indian
      adults with low vitamin B12.
AB  - CONTEXT: Plasma total homocysteine (tHcy) is higher in men than women. OBJECTIVE:
      To explore the gender differences in tHcy in relation to determinants of one
      carbon metabolism in Indian people with low B12 and adequate folate. SETTING: The
      study took place in rural and urban areas of Pune, India. DESIGN AND
      PARTICIPANTS: Participants were 441 men from the cross-sectional Coronary Risk of
      Insulin Sensitivity in Indian Subjects study (CRISIS) and premenopausal wives of
      146 men (median ages 38 and 34 years, respectively). MAIN OUTCOME MEASURES:
      Gender difference in fasting tHcy in relation to plasma albumin and creatinine
      concentrations, lifestyle factors, diet and lean mass, plasma B12 and red cell
      folate (RCF) was assessed. RESULTS: Prevalence of high tHcy (> 15 umol/L, median
      14.4 uM) was 40 %, low B12 (< 150 pmol/L, 114 pmol/L) 66 %, and low RCF (< 283
      nmol/L, 525 nmol/L) 8 %. Men had higher (1.8x) plasma tHcy concentrations (16.2
      umol/L) than women (9.5 umol/L). Only 50 % of the gender difference was explained
      by age, lean mass, B12, and RCF. The difference remained after controlling for
      other explanatory variables. Women with a tHcy of 9.3 uM had the same B12
      concentration (129 pmol/L) as men with a tHcy of 15 uM; and for a tHcy of 10.0
      umol/L women had the same RCF concentration (533 nmol/L) as men with a tHcy of 15
      umol/L. CONCLUSIONS: Adult Indian women have markedly lower tHcy concentrations
      compared to men. This suggests a lower threshold for supplementation to improve
      reproductive and cardiovascular outcomes.

PMID- 22419202
TI  - Serum 25-hydroxyvitamin D levels in subjects with reduced glucose tolerance and
      type 2 diabetes - the Tromso OGTT-study.
AB  - The relationships between vitamin D concentrations, hyperglycemia, and insulin
      resistance remain uncertain. During 2008 - 2010, an oral glucose tolerance test
      was performed in 3520 subjects from Tromso, Norway. Serum 25-hydroxyvitamin D
      [25(OH)D] was measured in 1193 subjects with normal glucose tolerance, in 304
      with isolated impaired fasting glucose, in 254 with isolated impaired glucose
      tolerance, in 139 with a combination of the two, and in 194 subjects with type 2
      diabetes. Serum 25(OH)D did not differ between subjects with isolated impaired
      fasting glucose or impaired glucose tolerance, but was lower in all groups of
      deranged glucose metabolism as compared with normal subjects. These differences
      could not be explained by differences in intakes of vitamin D from cod liver oil
      or other supplements and remained statistically significant after adjustment for
      gender, age, body mass index, physical activity score, and month of examination.
      When the cohort was divided according to serum 25(OH)D quartiles, there was an
      improvement in all measures of glucose metabolism (fasting and 2-hour plasma
      glucose, serum insulin, HbA(1c)) and estimates of insulin resistance (QUICKI ,
      HOMA-IR, ISI(0.120)) with increasing serum 25(OH)D quartile. However,
      interventional studies are needed to prove a causal relationship between vitamin
      D and glucose metabolism.

PMID- 22419203
TI  - Nutritional B12 deficiency in infants of vitamin B12-deficient mothers.
AB  - AIM: Nutritional vitamin B12 deficiency in infants may occur because the maternal
      diet contains inadequate animal products. Clinical presentations of the infants
      who had nutritional vitamin B12 deficiency were analyzed in this study. SUBJECTS
      AND METHODS: Patients with nutritional vitamin B12 deficiency were enrolled in
      the study between 2003 and 2010. The diagnosis was based on a nutritional history
      of mothers and infants, clinical findings, hematological evaluation, and low
      level of serum vitamin B12. RESULTS: Thirty children aged 1 - 21 months
      constituted the study group. Poverty was the main cause of inadequate consumption
      of animal products of the mothers. All infants had predominantly breastfed. The
      most common symptoms were developmental delay, paleness, apathy, lethargy,
      anorexia, and failure to thrive. Hematological findings were megaloblastic anemia
      (83.3 %), thrombocytopenia (30 %), and severe anemia (13.3 %). All of the mothers
      had low serum B12 levels; eight of them had megaloblastic anemia. CONCLUSION: The
      unusual clinical manifestations of vitamin B12 deficiency may also be seen apart
      from neurological and hematological findings. Nutritional vitamin B12 deficiency
      due to maternal deficiency might be a serious health problem in infants.
      Therefore, screening and supplementation of pregnant and lactating women to
      prevent infantile vitamin B12 deficiency should be considered.

PMID- 22419204
TI  - Quantification of vitamin a in palm oil using a fast and simple portable device:
      method validation and comparison to high-performance liquid chromatography.
AB  - Vitamin A deficiency continues to be a global public health problem.
      Fortification of oil with vitamin A is considered a cost-effective, feasible
      strategy to prevent this problem but quality control poses a challenge to program
      implementation. To overcome this, we have validated a newly developed device that
      quantitatively measures the content of retinyl palmitate in refined palm oil, is
      simple to use, and yields immediate results.Linearity of analysis ranged from 2.5
      - 30 mg retinol equivalents (RE)/ kg of palm oil, with 2.5 mg RE/kg being the
      determination limit; inter- and intra-assay precision ranged from 1.4 - 7.1 %.
      Comparison with a high-performance liquid chromatography method showed high
      agreement between the methods (R(2) = 0.92; Limits of Agreement: -1.24 mg to 2.53
      mg RE/kg), and further comparisons illustrate that the new device is useful in
      low-resource settings. This device offers a field- and user-friendly solution to
      quantifying the vitamin A content in refined palm oil.

PMID- 22419206
TI  - Graphene.

PMID- 22419205
TI  - Association of the physical and chemical properties and the cytotoxicity of metal
      oxide nanoparticles: metal ion release, adsorption ability and specific surface
      area.
AB  - Association of cellular influences and physical and chemical properties were
      examined for 24 kinds of industrial metal oxide nanoparticles: ZnO, CuO, NiO,
      Sb(2)O(3), CoO, MoO(3), Y(2)O(3), MgO, Gd(2)O(3), SnO(2), WO(3), ZrO(2),
      Fe(2)O(3), TiO(2), CeO(2), Al(2)O(3), Bi(2)O(3), La(2)O(3), ITO, and cobalt blue
      pigments. We prepared a stable medium dispersion for each nanoparticle and
      examined the influence on cell viability and oxidative stress together with
      physical and chemical characterizations. ZnO, CuO, NiO, MgO, and WO(3) showed a
      large amount of metal ion release in the culture medium. The cellular influences
      of these soluble nanoparticles were larger than insoluble nanoparticles. TiO(2),
      SnO(2), and CeO(2) nanoparticles showed strong protein adsorption ability;
      however, cellular influences of these nanoparticles were small. The primary
      particle size and the specific surface area seemed unrelated to cellular
      influences. Cellular influences of metal oxide nanoparticles depended on the kind
      and concentrations of released metals in the solution. For insoluble
      nanoparticles, the adsorption property was involved in cellular influences. The
      primary particle size and specific surface area of metal oxide nanoparticles did
      not affect directly cellular influences. In conclusion the most important
      cytotoxic factor of metal oxide nanoparticles was metal ion release.

PMID- 22419207
TI  - Materials science: Super carbon.

PMID- 22419208
TI  - Production: Beyond sticky tape.

PMID- 22419209
TI  - Electronics: Back to analogue.

PMID- 22419211
TI  - Come into the light.

PMID- 22419210
TI  - Bioelectronics: The bionic material.

PMID- 22419212
TI  - Q&A: Taking charge. Interview by Peter Gwynne.

PMID- 22419213
TI  - Perspective: A means to an end.

PMID- 22419214
TI  - Material history: Learning from silicon.

PMID- 22419215
TI  - Parameter estimation in spiking neural networks: a reverse-engineering approach.
AB  - This paper presents a reverse engineering approach for parameter estimation in
      spiking neural networks (SNNs). We consider the deterministic evolution of a time
      discretized network with spiking neurons, where synaptic transmission has delays,
      modeled as a neural network of the generalized integrate and fire type. Our
      approach aims at by-passing the fact that the parameter estimation in SNN results
      in a non-deterministic polynomial-time hard problem when delays are to be
      considered. Here, this assumption has been reformulated as a linear programming
      (LP) problem in order to perform the solution in a polynomial time. Besides, the
      LP problem formulation makes the fact that the reverse engineering of a neural
      network can be performed from the observation of the spike times explicit.
      Furthermore, we point out how the LP adjustment mechanism is local to each neuron
      and has the same structure as a 'Hebbian' rule. Finally, we present a
      generalization of this approach to the design of input-output (I/O)
      transformations as a practical method to 'program' a spiking network, i.e. find a
      set of parameters allowing us to exactly reproduce the network output, given an
      input. Numerical verifications and illustrations are provided.

PMID- 22419216
TI  - Minimizing nitrous oxide in biological nutrient removal from municipal wastewater
      by controlling copper ion concentrations.
AB  - In this study, nitrous oxide (N(2)O) production during biological nutrient
      removal (BNR) from municipal wastewater was reported to be remarkably reduced by
      controlling copper ion (Cu(2+)) concentration. Firstly, it was observed that the
      addition of Cu(2+) (10-100 MUg/L) reduced N(2)O generation by 54.5-73.2 % and
      improved total nitrogen removal when synthetic wastewater was treated in an
      anaerobic-aerobic (with low dissolved oxygen) BNR process. Then, the roles of
      Cu(2+) were investigated. The activities of nitrite and nitrous oxide reductases
      were increased by Cu(2+) addition, which accelerated the bio-reductions of both
      nitrite to nitric oxide (NO (2) (-) -> NO) and nitrous oxide to nitrogen gas
      (N(2)O -> N(2)). The quantitative real-time polymerase chain reaction assay
      indicated that Cu(2+) addition increased the number of N(2)O reducing
      denitrifiers. Further investigation showed that more polyhydoxyalkanoates were
      utilized in the Cu(2+)-added system for denitrification. Finally, the feasibility
      of reducing N(2)O generation by controlling Cu(2+) was examined in two other BNR
      processes treating real municipal wastewater. As the Cu(2+) in municipal
      wastewater is usually below 10 MUg/L, according to this study, the supplement of
      influent Cu(2+) to a concentration of 10-100 MUg/L is beneficial to reduce N(2)O
      emission and improve nitrogen removal when sludge concentration in the BNR system
      is around 3,200 mg/L.

PMID- 22419217
TI  - Role and fate of SP100 protein in response to Rep-dependent nonviral integration
      system.
AB  - Previously, we studied an AAVS1 site-specific non-viral integration system with a
      Rep-donor plasmid and a plasmid containing adeno-associated virus integration
      element. Our earlier study focused on the plasmid vector itself, but the cellular
      response to the system was still unknown. SP100 is a member of the promyelocytic
      leukemia nuclear bodies. It is involved in many cellular processes such as
      transcriptional regulation and the cellular intrinsic immune response against
      viral infection. In this study, we revealed that SP100 inhibited the Rep
      dependent nonviral integration. Conversely, transient expression of Rep78
      increased the degradation of SP100. This degradation was inhibited by treatment
      with MG132, an inhibitor of the ubiquitin proteasome. SP100 and Rep78 are both
      located in the nucleolus, which provides the spatial possibility for their
      interaction. Rep78 was coimmunoprecipitated with the enhanced green fluorescent
      protein (EGFP)-SP100 fusion protein but not EGFP, which verified the interaction
      between Rep78 and SP100. These results have enriched our knowledge about the
      cellular protein SP100 and Rep-dependent nonviral integration. It may lead to an
      improvement in the application of Rep-related transgene integration method and in
      the selection of target cells.

PMID- 22419218
TI  - Immobilization of glucoamylase onto polyaniline-grafted magnetic hydrogel via
      adsorption and adsorption/cross-linking.
AB  - Glucoamylase (GA) was immobilized onto polyaniline (PANI)-grafted magnetic poly(2
      hydroxyethylmethacrylate-co-glycidylmethacrylate) hydrogel (m-p(HEMA-GMA)-PANI)
      with two different methods (i.e., adsorption and adsorption/cross-linking). The
      immobilized enzyme preparations were used for the hydrolysis of "starch" dextrin.
      The amount of enzyme loading on the ferrogel was affected by the medium pH and
      the initial concentration of enzyme. The maximum loading capacity of the enzyme
      on the ferrogel was found to be 36.7 mg/g from 2.0 mg/mL enzyme solution at pH
      4.0. The adsorbed GA demonstrated higher activity (59%) compared to
      adsorbed/cross-linked GA (43%). Finally, the immobilized GA preparations
      exhibited greater stability against heat at 55  degrees C and pH 4.5 compared to
      free enzyme (50  degrees C and pH 5.5), suggesting that the ferrogel was suitable
      support for immobilization of glucoamylase.

PMID- 22419219
TI  - Ultraviolet-B light treatment increases antioxidant capacity of carrot products.
AB  - BACKGROUND: The effect of ultraviolet-B (UV-B) light as a postharvest treatment
      to enhance the antioxidant content of carrots and fresh-cut carrot products was
      evaluated. Four levels of UV-B dose ranging from 1.3 to 12 kJ m-2 were applied to
      whole, baby and various styles of cut carrots, and the changes in antioxidant
      capacity, total soluble phenolics and phenylalanine ammonia-lyase (PAL, EC
      4.3.1.24) activity were measured after a 3 day incubation period at 15  degrees C
      and 45% relative humidity. RESULTS: Both cutting style and dose level were
      factors in determining carrot responses to UV-B treatment. Antioxidant capacity
      increased significantly (1.4-6.6-fold). Total soluble phenolic results correlated
      directly with those of antioxidant capacity (R2 = 0.953), indicating that the
      enhancements achieved were due to an increase in phenolic content. High
      performance liquid chromatography analysis revealed that 5-O-caffeoylquinic acid
      (5-CQA) was the primary phenolic responsible for this increase. Higher PAL
      activity was also observed in UV-B-treated samples, indicating that the increase
      in 5-CQA was a biological response to UV-B exposure. CONCLUSION: UV-B treatment
      has the potential to increase the nutritional value of carrots and offers an
      exciting opportunity to increase consumer accessibility to dietary choices that
      are rich in antioxidants.

PMID- 22419220
TI  - A Ser/Thr protein kinase phosphorylates MA-ACS1 (Musa acuminata 1
      aminocyclopropane-1-carboxylic acid synthase 1) during banana fruit ripening.
AB  - 1-Aminocyclopropane-1-carboxylic acid synthase (ACS) catalyzes the rate-limiting
      step in ethylene biosynthesis during ripening. ACS isozymes are regulated both
      transcriptionally and post-translationally. However, in banana, an important
      climacteric fruit, little is known about post-translational regulation of ACS.
      Here, we report the post-translational modification of MA-ACS1 (Musa acuminata
      ACS1), a ripening inducible isozyme in the ACS family, which plays a key role in
      ethylene biosynthesis during banana fruit ripening. Immunoprecipitation analyses
      of phospholabeled protein extracts from banana fruit using affinity-purified anti
      MA-ACS1 antibody have revealed phosphorylation of MA-ACS1, particularly in ripe
      fruit tissue. We have identified the induction of a 41-kDa protein kinase
      activity in pulp at the onset of ripening. The 41-kDa protein kinase has been
      identified as a putative protein kinase by MALDI-TOF/MS analysis. Biochemical
      analyses using partially purified protein kinase fraction from banana fruit have
      identified the protein kinase as a Ser/Thr family of protein kinase and its
      possible involvement in MA-ACS1 phosphorylation during ripening. In vitro
      phosphorylation analyses using synthetic peptides and site-directed mutagenized
      recombinant MA-ACS1 have revealed that serine 476 and 479 residues at the C
      terminal region of MA-ACS1 are phosphorylated. Overall, this study provides
      important novel evidence for in vivo phosphorylation of MA-ACS1 at the molecular
      level as a possible mechanism of post-translational regulation of this key
      regulatory protein in ethylene signaling pathway in banana fruit during ripening.

PMID- 22419221
TI  - Within- and between-species study of extreme longevity--comments, commonalities,
      and goals.

PMID- 22419222
TI  - Liver X receptors, atherosclerosis and inflammation.
AB  - Liver X receptors (LXRs) belong to the nuclear receptor superfamily of ligand
      dependent transcription factors. LXRs are activated by oxysterols, metabolites of
      cholesterol, and therefore act as intracellular sensors of this lipid. There are
      two LXR genes (alpha and beta) that display distinct tissue/cell expression
      profiles. LXRs interact with regulatory sequences in target genes as heterodimers
      with retinoid X receptor. Such direct targets of LXR actions include important
      genes implicated in the control of lipid homeostasis, particularly reverse
      cholesterol transport. In addition, LXRs attenuate the transcription of genes
      associated with the inflammatory response indirectly by transrepression. In this
      review, we describe recent evidence that both highlights the key roles of LXRs in
      atherosclerosis and inflammation and provides novel insights into the mechanisms
      underlying their actions. In addition, we discuss the major limitations of LXRs
      as therapeutic targets for the treatment of atherosclerosis and how these are
      being addressed.

PMID- 22419223
TI  - The CCL2-CCR2 system affects the progression and clearance of intracerebral
      hemorrhage.
AB  - Intracerebral hemorrhage (ICH) has been associated with inflammation and
      apoptosis. The CCL2-CCR2 chemotactic system is one of the major signaling
      pathways that induce inflammation and apoptosis. However, its role on ICH has not
      been investigated. We subjected wild-type, CCL2(-/-) , and CCR2(-/-) mice to
      collagenase-induced ICH, and assessed histological and behavioral outcomes. Lack
      of CCL2 or CCR2 decreased the hematoma volume early after collagenase-induced ICH
      but delayed its recovery. The hematoma size was accompanied by brain edema,
      neuronal death, and neurological scores. Although microglia activation/migration
      was attenuated in CCL2(-/-) or CCR2(-/-) mice 1 day after injury, more microglia
      were present at later time points, suggesting that alternative signaling pathways
      had been activated to recruit them. On the contrary, leukocyte and neutrophil
      infiltration were decreased in these mice, suggesting a tighter/recovered blood
      brain barrier. In addition, we also found that FL- and K104Stop-CCL2 were able to
      restore the changes found in CCL2(-/-) mice, but K104A-CCL2 failed to do so.
      These results suggest that plasmin-mediated truncation of CCL2 may be an
      indispensable step to fully activate the chemokine in vivo. The data also
      indicate that CCL2-CCR2 signaling pathway may be a molecular target for the
      treatment of ICH.

PMID- 22419224
TI  - Automatic alignment of myocardial perfusion PET and 64-slice coronary CT
      angiography on hybrid PET/CT.
AB  - BACKGROUND: Hybrid PET/CT allows for acquisition of cardiac PET and coronary CT
      angiography (CCTA) in one session. However, PET and CCTA are acquired with
      differing breathing protocols and require software registration. We aimed to
      validate automatic correction for breathing misalignment between PET and CCTA
      acquired on hybrid scanner. METHODS: Single-session hybrid PET/CT studies of
      rest/stress (13)N-ammonia PET and CCTA in 32 consecutive patients were
      considered. Automated registration of PET left ventricular (LV) surfaces with
      CCTA volumes was evaluated by comparing with expert manual alignment by two
      observers. RESULTS: The average initial misalignments between the position of LV
      on PET and CCTA were 27.2 +/- 11.8, 13.3 +/- 11.5, and 14.3 +/- 9.1 mm in x, y,
      and z axes on rest, and 26.3 +/- 10.2, 11.1 +/- 9.5, and 11.7 +/- 7.1 mm in x, y,
      and z axes on stress, respectively. The automated PET-CCTA co-registration had
      95% agreement as judged visually. Compared with expert manual alignment, the
      translation errors of the algorithm were 5.3 +/- 2.8 mm (rest) and 6.0 +/- 3.5 mm
      (stress). 3D visualization of combined coronary vessel anatomy and hypoperfusion
      from PET could be made without further manual adjustments. CONCLUSION: Software
      co-registration of CCTA and PET myocardial perfusion imaging on hybrid PET/CT
      scanners is necessary, but can be performed automatically, facilitating
      integrated 3D display on PET/CT.

PMID- 22419225
TI  - What matters in measuring methamphetamine-related cognitive impairments:
      'abnormality detection' versus 'everyday import'?

PMID- 22419228
TI  - Antimicrobial activity of Chinese bayberry extract for the preservation of
      surimi.
AB  - BACKGROUND: Chemical preservatives such as sodium nitrite and potassium sorbate
      have been widely used to keep surimi products fresh. However, the potential
      harmfulness to human health cannot be ignored. This study was conducted to
      develop natural preservatives for the storage of Collichthys surimi. RESULTS:
      Among the eight Chinese traditional herbs and fruits, Chinese bayberry extract
      showed the greatest inhibitory effect against surimi spoilage bacteria Serratia
      marcescens and Pseudomonas aeruginosa. Moreover, N-butanol phase extract of
      bayberry (NB) showed the greatest activity among the different phases of bayberry
      extract. When Chinese bayberry extract was combined with tea polyphenol, an
      additive inhibitory effect was observed on growth of Hansenula anomala,
      Micrococcus luteus, Staphylococcus aureus, Pseudomonas aeruginosa, and
      Escherichia coli. Our results further indicated that the shelf life of surimi
      products stored at room temperature can be extended when supplemented with
      Chinese bayberry extract. CONCLUSION: Our results suggest that Chinese bayberry
      extract can be used as a natural preservative for the storage of Collichthys
      surimi.

PMID- 22419229
TI  - In vivo screening of zebrafish microRNA responses to bacterial infection and
      their possible roles in regulating immune response genes after lipopolysaccharide
      stimulation.
AB  - Micro (mi)RNAs are abundant small noncoding RNAs found in plants and animals, the
      regulatory functions of which are not fully understood in fish. To identify
      potential miRNAs, we screened an miRNA microarray with total RNA from zebrafish
      infected with Vibrio harveyi and another from uninfected zebrafish. Six miRNAs
      were obtained from the microarray screening. We studied miRNA expression patterns
      of 2 miRNAs (miR-122 and miR-194) after bacterial infection of transgenic
      zebrafish (containing tilapia hepcidin (TH)2-3) and non-transgenic zebrafish from
      which the 2 miRNAs were obtained from the microarray experiment. The results
      indicated that miR-122 and miR-194 were higher in PBS-injected zebrafish compared
      with TH2-3 zebrafish or wild-type (WT) zebrafish after V. harveyi infection.
      Overexpression of miRNAs (miR-122, miR-192, and miR-194a) was seen in zebrafish
      liver (ZFL) cells after lipopolysaccharide (LPS) treatment and in untreated fish.
      Our results showed that after 24 h of doxycycline treatment without LPS
      stimulation, interleukin (IL)-22, lysozyme, toll-like receptor (TLR)1, TLR3,
      TLR4a, and tumor necrosis factor (TNF)-alpha gene expressions were, respectively,
      upregulated by ~14-, 22-, 2.2-, 13-, 200-, and 38-fold in miR-122-transfected
      compared with non-transfected (WT) ZFL cells. In cells transfected with miR-192
      and treated with LPS after 8-12 h, IL-22, lysozyme, TLR1, TLR3, TLR4a, and TNF
      alpha expressions significantly differed between WT and miR-192-overexpressing
      ZFL cells. However, we observed significantly higher IL-22 expression levels
      after 12 h of LPS treatment in miR-192-transfected ZFL cells compared with non
      transfected cells. In contrast, IL-22, lysozyme, and TNF-alpha were markedly
      upregulated (>100-fold) after miR-194a transfection and overexpression in ZFL
      cells and treatment with LPS. Our cloning and expression analyses indicated that
      miR-122, miR-192, and miR-194a play important roles in zebrafish immunology.

PMID- 22419232
TI  - Variability of blood pressure in dialysis patients: a new marker of
      cardiovascular risk.
AB  - BACKGROUND: Hemodialysis patients have a high cardiovascular mortality, and
      hypertension is the most prevalent treatable risk factor. We aimed to assess the
      predictive significance of dialysis-to-dialysis variability in blood pressure in
      hemodialysis patients. METHODS: We performed a historical cohort study in 1,088
      prevalent hemodialysis patients, followed up for 5 years. The risk of
      cardiovascular death was determined in relation to dialysis-to-dialysis
      variability in blood pressure, maximum blood pressure and pulse pressure.
      RESULTS: Variability in blood pressure was a predictor of cardiovascular death
      (hazard ratio [HR] = 1.242; 95% confidence interval [95% CI], 1.004-1.537;
      p=0.046). Also age (HR=1.021; 95% CI, 1.011-1.048; p=0.049), diabetes (HR=1.134;
      95% CI, 1.128-1.451; p=0.035), creatinine (HR=0.837; 95% CI, 0.717-0.977;
      p=0.024) and albumin (HR=0.901; 95% CI, 0.821-0.924; p=0.022) influenced
      mortality. Maximum blood pressure and pulse pressure did not show any effect on
      cardiovascular death. CONCLUSION: Dialysis-to-dialysis variability in blood
      pressure is a predictor of cardiovascular mortality in hemodialysis patients, and
      blood pressure variability may be used in managing hypertension and predicting
      outcomes in dialysis patients.

PMID- 22419230
TI  - NDM-1 and the Role of Travel in Its Dissemination.
AB  - Antimicrobial resistance is a growing problem globally. The appearance and spread
      of bacteria that are resistant to most or all commonly available antibiotics has
      raised the specter of untreatable bacterial infections. The New Delhi metallo
      beta-lactamase-1 (NDM-1) has received wide attention because of the extreme
      resistance it confers, its presence in many common pathogens, its rapid spread to
      multiple continents, and local nosocomial spread in some areas. Most early
      reports of infections were in individuals who had received medical care in the
      Indian subcontinent. This paper will explore the role of travelers in the
      movement of pathogens and microbial genetic material associated with resistance,
      with a special focus on the appearance and dispersal of bacteria carrying this
      mobile genetic element, bla (NDM-1), and the contributing factors, including
      growing long-distance travel and expansion of travel across international borders
      for medical, dental, and surgical care (medical tourism).

PMID- 22419233
TI  - Pitfall in nephrology: contrast nephropathy has to be differentiated from renal
      damage due to atheroembolic disease.
AB  - INTRODUCTION: The topic of contrast-induced nephropathy (CIN) has been receiving
      an enormous amount of interest in recent times; however, this review is not a
      review of what CIN is, but what it is not. METHODS: We will review the main
      topics demonstrating that the post hoc ergo propter hoc assumption that renal
      impairment occurring after contrast medium (CM) infusion is necessarily because
      of it, is wrong, as we are dealing with different diseases, depending on the way
      the CM is administered and on the type of patient. RESULTS: After >1,000 often
      repetitive papers, we must deal with an unacceptably wide range of incidences of
      CIN, with completely different prognoses and astonishingly conflicting results
      regarding the efficacy of preventive measures with the exception of hydration. So
      what went wrong? How to separate tares from wheat? When years ago we challenged
      the diagnosis of CIN, the words cholesterol embolism had never appeared in this
      setting. Now, we can split the possible renal dysfunctions following CM
      administration into CM-related hemodynamic and/or tubular damage, cholesterol
      embolism, ischemia from acute blood loss or hypotension/hypoperfusion and
      nephrotoxicity from concomitant drugs. CONCLUSIONS: In a setting regarding
      millions of patients and millions of dollars/year, in order to clarify the true
      renal damage directly related to CM, we ask for prospective studies
      differentiating cohorts receiving intravenous and intra-arterial, transradial and
      transfemoral injections, and clinically relevant renal outcomes, thus avoiding
      the dangers that can come from the idolatry of a surrogate end point such an
      asymptomatic 25% transient increase of serum creatinine. To avoid that, patients
      may lose the possibility of a more useful radiological diagnosis, because of an
      exaggerated suspicion of risk.

PMID- 22419234
TI  - Interaction among medical specialists.

PMID- 22419235
TI  - Trends in the incidence of intestinal perforation in US dialysis patients (1992
      2005).
AB  - BACKGROUND: Little is known about the incidence of intestinal perforation in
      patients undergoing dialysis. Concerns exist that sevelamer hydrochloride may
      increase the risk of intestinal perforation. We examined long-term trends for the
      incidence of intestinal perforation among US dialysis patients. METHODS: We
      studied all dialysis patients (1992-2005) who had Medicare as primary payer. We
      used ICD-9 diagnosis code 569.83 to ascertain events of intestinal perforation.
      We studied (a) all perforations and (b) perforations that did not appear to be
      associated with specific causative conditions (specific diseases or iatrogenic
      procedures within 7 days of perforation). We used Poisson regression to model the
      annual number of intestinal perforations and tested for any changes in levels and
      temporal trends of incidence rates before versus after January 1, 1999. RESULTS:
      Overall, 1,060,132 patients contributed 2.7 million patient-years. We observed
      12,355 events of intestinal perforation and 7,814 spontaneous perforations. The
      corresponding incidence rates were 4.6 (total) and 2.9 (spontaneous perforation)
      episodes per 1,000 person-years, respectively. For both outcome definitions, 30
      day mortality was 42%. Unadjusted and adjusted incidence rates were not
      materially different over time. Formal tests for any changes in the level or
      slope of incidence comparing time periods before and after January 1, 1999,
      indicated no evidence for any changes in the incidence of intestinal perforation
      over time. CONCLUSIONS: In US dialysis patients, incidence of intestinal
      perforation was low, but associated with high short-term mortality. We did not
      detect any significant changes in the incidence of intestinal perforation before
      versus after approval of sevelamer hydrochloride in late 1998.

PMID- 22419236
TI  - Dermatan sulfate: an alternative to unfractionated heparin for anticoagulation in
      hemodialysis patients.
AB  - BACKGROUND: Unfractionated heparin (UFH) is the standard anticoagulant in regular
      dialysis treatments (RDTs), despite the fact that it may induce thrombocytopenia,
      dyslipidemia, allergy and osteoporosis. Dermatan sulfate (DS) selectively
      inhibits thrombin, does not inhibit F-Xa and does not interfere with platelets
      (PLTS). Here we described an original protocol for the use of DS as anticoagulant
      in RDT and compared its effects with those of UFH. METHODS: In 102 patients,
      7,254 RDTs were performed using DS for anticoagulation (DS-phase) and 5,707 with
      UFH (UFH-phase). DS was supplied as initial bolus (80 +/- 12 mg) and continuous
      infusion (14 +/- 7 mg/hour). With UFH, the initial bolus was 1,475 +/- 141 IU and
      continuous infusion 576 +/- 349 IU/hour. Activated partial thromboplastin time
      and its ratio were measured at least monthly, both before (pre-RDT APTT ratio)
      and after (post-RDT APTT ratio) RDT sessions. With 41 of 102 patients, both DS
      and UFH doses were not changed during study phases (stable patients). In this
      subset, the coefficient of variation (CV) of all pre-RDT APTT ratio and post-RDT
      APTT ratio values was calculated. RESULTS: In DS and UFH phases, post-RDT APTT
      ratio increased by 61% and 50%, respectively, by comparison with pre-RDT APTT
      ratio (p<0.001). PLTS count was lower in the UFH than in the DS phase (p<0.01).
      In stable patients, post-RDT APTT ratio CV was lower in the DS than in the UFH
      phase (p<0.001), which indicates a more predictable anticoagulant effect of DS
      compared with UFH. CONCLUSIONS: DS appeared as effective as UFH for
      anticoagulation in RDT. It can reliably be considered as an alternative approach
      especially in cases of thrombocytopenia or other adverse effects of UFH.

PMID- 22419237
TI  - Thyroid function tests in acute kidney injury.
AB  - OBJECTIVE: The aim of this study was to analyze the prevalence, clinical
      significance and prognostic implications of alterations in thyroid function tests
      (TFTs) in patients with acute kidney injury (AKI). METHODS: A prospective study
      was carried out in patients hospitalized for AKI for 2 consecutive years. TFTs
      (serum thyrotropin [TSH], free thyroxine [FT4] and total triiodothyronine [T3]
      concentrations) were completed for each patient on 3 occasions: at admission, at
      hospital discharge and at their first outpatient visit. TFTs were related to
      clinical and analytical data. Thirty-five patients (16 women [45.7%], mean age +/
      SD, 65.2 +/- 18.0 years) with AKI (creatinine 5.6 +/- 2.2 mg/dL) were studied.
      There were 10 (28.6%), 10 (28.6%), 11 (31.4%) and 4 (11.4%) patients with
      prerenal, renal, mixed (prerenal and renal), and postrenal AKI, respectively.
      RESULTS: Total prevalence of alterations in TFTs was 82.9% (n=29). Of those,
      euthyroid sick syndrome (ESS) with low T3 only was the most common (n=13, 37.1%)
      derangement. In the whole group of patients, median TSH (0.93 uU/mL,
      interquartile range 0.35-2.27 uU/mL)and mean FT4 (1.2 +/- 0.3 ng/dL) were normal,
      whereas mean T3 was low (0.7 +/- 0.1 ng/mL). TSH, FT4 and T3 were similar in
      different types of AKI. On simple regression analysis, we found a negative
      correlation only between TSH and serum urea concentrations (ro=-0.382; p=0.024).
      At hospital discharge (median hospital stay 6 days; range 2-10 days), TFT showed
      significant changes only in T3 concentrations (0.8 +/- 0.3 ng/mL, p=0.013). At
      this point, the percentage of patients with normal TFT increased from 17.1% at
      baseline to 40% at discharge and then to 66.7% at their first outpatient visit.
      We found no association between the presence and type of alterations in TFT and
      clinical factors (sex, age, personal history of diabetes and/or hypertension,
      number and type of drugs used, number of signs and symptoms at AKI diagnosis, and
      degree, type and cause of AKI) or prognostic factors (hospital stay, recovery of
      renal function, need for renal replacement therapy by hemodialysis, development
      and degree of residual chronic renal failure and mortality) associated with AKI.
      CONCLUSION: Over 80% of AKI patients exhibit alterations in TFT. The commonest
      derangement is ESS (~70%), mainly low T3 syndrome, which is present in about one
      third of the patients with altered TFT. ESS recovers spontaneously as renal
      function improves. The presence of TFT alterations seems to not be associated
      with clinical and prognostic implications in AKI patients.

PMID- 22419238
TI  - Rehabilitation strategy in the elderly.
AB  - The population is getting older. Rehabilitation can play an essential strategic
      role to counteract impairments and disability which characterize the elderly.
      Correct rehabilitative programmes have to be approached on the functional
      limitation and residual abilities of elders. Leading a more active lifestyle and
      regular physical activity including aerobic and resistance exercises have been
      demonstrated to improve cardiovascular, respiratory, musculoskeletal, and
      cognitive wellbeing in older adults. Occupational therapy, prescription of
      assistive devices, environmental, and home living adaptation, and family or
      caregiver educational training represent an essential rehabilitative strategy in
      elders developing disability. In these people, falls are dramatic events that
      lead to hospitalization, functional decline, decreased social activity, and poor
      quality of life. Rehabilitation incorporating balance, gait, and strength
      training exercise interventions can reduce the risk of falls. Frailty refers to a
      condition characterized by a gradual physiologic decline in multiple body
      systems, loss of physiologic reserve, and increased vulnerability to disease and
      death. Several therapeutic strategies have been proposed including exercises,
      multi-component training and approaches, all aimed at decreasing the need for
      nursing home placement, hospitalization, and reducing dependence and death. In
      these subjects, geriatric comprehensive assessment and the multi-disciplinary
      team have recently been demonstrated to be more effective than usual care.

PMID- 22419239
TI  - Structural diversity of nuptial pads in Phyllomedusinae (Amphibia: Anura:
      Hylidae).
AB  - We studied the morphological variation of the nuptial pads using light microscopy
      and scanning electron microscopy (SEM) in 26 species of phyllomedusines (Anura:
      Hylidae), representing the five currently recognized genera. All phyllomedusines
      have single nuptial pads with dark colored epidermal projections (EPs). Spine
      shaped EPs occur in Cruziohyla calcarifer, Phrynomedusa appendiculata and in one
      species of Phasmahyla. The other species have roundish EPs. The density of the
      EPs on the pad is variable. Species in the Phyllomedusa hypochondrialis Group
      have EPs with a density that varies between 764 +/- 58/mm(2) and 923 +/-
      160/mm(2). In all other studied species (including the Phyllomedusa burmeisteri
      and Phyllomedusa perinesos groups, Phyllomedusa camba, Phyllomedusa boliviana,
      Phyllomedusa sauvagii, Phyllomedusa bicolor, and Phyllomedusa tomopterna) the
      density of EPs varies between 108 +/- 20/mm(2) and 552 +/- 97/mm(2). Pores were
      observed with SEM in C. calcarifer, Agalychnis lemur, Agalychnis moreletii, but
      its presence is confirmed through histological sections on several other species.
      Its visibility using SEM seems to be related with the level of separation between
      adjacent EPs. The pores in the four studied species of Agalychnis are shown with
      SEM and histological sections to have a characteristic epidermal rim, that is
      absent in the otherphyllomedusines. Unlike most previous reports on breeding
      glands, those of phyllomedusines are alcian blue positive, indicating the
      presence of acidic mucosubstances on its secretions.

PMID- 22419240
TI  - A genomewide survey of bHLH transcription factors in the coral Acropora
      digitifera identifies three novel orthologous families, pearl, amber, and
      peridot.
AB  - Decoding the genome of the coral, Acropora digitifera, enabled us to characterize
      a nearly full set of 70 basic helix-loop-helix (bHLH) transcription factors in
      this organism. This number is comparable to 68 bHLH genes in the sea anemone,
      Nematostella vectensis, and larger than those in most other invertebrate
      metazoans. The 70 bHLH genes were assigned to 29 orthologous families previously
      reported. In addition, we identified three novel HLH orthologous families, which
      we designated pearl, amber, and peridot, increasing the number of orthologous
      families to 32. Pearl and amber orthologues were found in genomes and expressed
      sequenced tags (ESTs) of Mollusca and Annelida in addition to Cnidaria. Peridot
      orthologues were found in genomes and ESTs of Cephalochordata and Hemichordata in
      addition to Cnidaria. These three genes were likely lost in the clades of
      Drosophila melanogaster, Caenorhabditis elegans, and Homo sapiens during animal
      evolution.

PMID- 22419242
TI  - Cardiovascular trials and diabetes treatments: a regulatory maze.

PMID- 22419243
TI  - 'Steinstrasse' in biliary tree - MRCP appearance.

PMID- 22419244
TI  - Hierarchically structured assembly of polymer microsieves, made by a combination
      of phase separation micromolding and float-casting.
AB  - Phase separation micromolding and float-casting are combined to prepare
      hierarchically structured microsieves.

PMID- 22419245
TI  - Physical and sensory characteristics of cookies prepared with flaxseed flour.
AB  - BACKGROUND: Flaxseed has many health benefits and is considered a functional food
      ingredient. Flaxseed flour (0-18%) was used to partially replace wheat flour in
      cookies and its effects on the physical and sensory characteristics of the
      cookies were investigated. A correlation analysis was conducted between the
      instrumental and sensory data. RESULTS: The cookie dough stickiness significantly
      (P < 0.05) decreased in relation to higher percentages of flaxseed flour. The 18%
      flaxseed cookies had the firmest texture, darkest color and lowest water
      activity. The 18% flaxseed cookies had the greatest spread ratio. However, this
      resulted in cookies of unacceptable quality properties. In consumer acceptance
      tests, cookies made with 6% and 12% flaxseed flour had the highest rating among
      all sensory attributes, while the 18% flaxseed cookies had the lowest sensory
      scores. The flavor attribute was most highly correlated with the overall
      acceptability (r = 0.90). CONCLUSION: Results indicated that flaxseed flour can
      be incorporated in cookies as a partial replacement up to 12% of wheat flour
      without negatively affecting the physical and sensory quality. The correlation
      results suggest that the flaxseed flavor attributes best predict consumer
      preference for overall acceptability, though texture and color attributes also
      contribute.

PMID- 22419246
TI  - Bias in relative survival methods when using incorrect life-tables: lung and
      bladder cancer by smoking status and ethnicity in New Zealand.
AB  - Relative survival and excess mortality approaches are commonly used to estimate
      and compare net survival from cancer. These approaches are based on the
      assumption that the underlying (non-cancer) mortality rate of cancer patients is
      the same as that of the general population. This assumption is likely to be
      violated particularly in the context of smoking-related cancers. The magnitude of
      this bias has not been estimated. The objective of this article is to estimate
      the bias in relative survival ratios (RSRs) and excess mortality rate ratios
      (EMRRs) from using total population compared to correct subpopulation specific
      life-tables. Analyses were conducted on 1996-2001 linked census-cancer data
      (including smoking status) for people with lung and bladder cancer, using sex
      specific (standard practice), sex- and ethnic-specific, sex- and smoking-specific
      and sex-, ethnic- and smoking-specific life-tables. Five-year RSRs using sex
      specific life-tables, compared to fully stratified life-tables, were
      underestimated by 10-25% for current smoking and Maori populations. For example,
      the current smoker male bladder cancer RSR was 0.700 for sex-specific life
      tables, compared to 0.838 for fully stratified life-tables. Similarly, EMRRs
      comparing current to never smokers and Maori to non-Maori were overestimated
      using sex-specific life-tables only: modestly only for lung cancer, but markedly
      for bladder cancer. For example, the EMRR comparing current to never smokers with
      bladder cancer in a fully adjusted regression model was 1.475 when using sex
      specific life-tables only, but reduced to 1.098 when using fully stratified life
      tables. Substantial bias can occur when estimating relative cancer survival
      across subpopulations if non-matching life-tables are used.

PMID- 22419247
TI  - A note on the topological insulator phase in non-Hermitian quantum systems.
AB  - Examples of non-Hermitian quantum systems admitting a topological insulator phase
      are presented in one, two and three space dimensions. All of these non-Hermitian
      Hamiltonians have entirely real bulk eigenvalues and unitarity is maintained with
      the introduction of appropriate inner products in the corresponding Hilbert
      spaces. The topological invariant characterizing a particular phase is shown to
      be identical for a non-Hermitian Hamiltonian and its Hermitian counterpart, to
      which it is related through a non-unitary similarity transformation. A
      classification scheme for topological insulator phases in pseudo-Hermitian
      quantum systems is suggested.

PMID- 22419248
TI  - Aging well and the environment: toward an integrative model and research agenda
      for the future.
AB  - PURPOSE OF THE STUDY: The effects of the physical-spatial-technical environment
      on aging well have been overlooked both conceptually and empirically. In the
      spirit of M. Powell Lawton's seminal work on aging and environment, this article
      attempts to rectify this situation by suggesting a new model of how older people
      interact with their environment. DESIGN AND METHODS: Goals of the paper include
      (a) integration of the essential elements of the ecology and aging literature,
      particularly in regard to Lawton's research, (b) development of connections
      between traditional theories of ecology of aging and life span developmental
      models of aging well, (c) acknowledgment of the pronounced historical and cohort
      related changes affecting the interactions of older people with their
      environment, and (d) discussion of the implications of this analysis for concepts
      and theories of aging well. RESULTS: The model builds on a pair of concepts:
      environment as related to agency and belonging, founded in motivational
      psychology, and developmental science. IMPLICATIONS: After describing the model's
      key components, we discuss its heuristic potential in four propositions for
      future gerontological research and identify implications of the model for future
      empirical research.

PMID- 22419249
TI  - Emotional reactivity to network stress in middle and late adulthood: the role of
      childhood parental emotional abuse and support.
AB  - PURPOSE: This study examined whether recalled childhood parental emotional abuse
      and support were associated with emotional reactivity to network stress among
      middle-aged and older adults. DESIGN AND METHODS: Hypotheses were tested by
      performing 2-level multilevel modeling analysis on 787 participants aged 33-83
      who participated in the Daily Stress Project (2004-2009). RESULTS: Adult
      daughters who recalled more childhood emotional abuse from their mother reported
      a higher average level of daily emotional distress nearly a decade later. The
      association between network stress and emotional distress was only significant
      among adult daughters. This emotional reactivity was attenuated by greater
      childhood emotional support from mothers. IMPLICATIONS: Recalled childhood mother
      child relationship continues to influence stress and coping across the lifespan,
      especially among women.

PMID- 22419250
TI  - Critical aspects in the production of periodically ordered mesoporous titania
      thin films.
AB  - Periodically ordered mesoporous titania thin films (MTTF) present a high surface
      area, controlled porosity in the 2-20 nm pore diameter range and an amorphous or
      crystalline inorganic framework. These materials are nowadays routinely prepared
      by combining soft chemistry and supramolecular templating. Photocatalytic
      transparent coatings and titania-based solar cells are the immediate promising
      applications. However, a wealth of new prospective uses have emerged on the
      horizon, such as advanced catalysts, perm-selective membranes, optical materials
      based on plasmonics and photonics, metamaterials, biomaterials or new magnetic
      nanocomposites. Current and novel applications rely on the ultimate control of
      the materials features such as pore size and geometry, surface functionality and
      wall structure. Even if a certain control of these characteristics has been
      provided by the methods reported so far, the needs for the next generation of
      MTTF require a deeper insight in the physical and chemical processes taking place
      in their preparation and processing. This article presents a critical discussion
      of these aspects. This discussion is essential to evolve from know-how to sound
      knowledge, aiming at a rational materials design of these fascinating systems.

PMID- 22419251
TI  - Exploiting thermoresponsive polymers to modulate lipophilicity: interactions with
      model membranes.
AB  - Upon heating above their lower critical solution temperature (LCST)
      poly[oligo(ethyleneglycol)methacrylate]s (POEGMA) were shown to undergo a shift
      in their partition coefficient triggering aqueous to organic phase transfer,
      which indicated their potential to partition into cell membranes upon application
      of an external stimulus. Fluorescence-based assays indicated that the LCST
      transition did not induce lysis of model phospholipid vesicles but did promote
      fusion, as confirmed by dynamic light scattering. Membrane perturbation assays
      and linear dichroism spectroscopy investigations suggest that POEGMAs above their
      transition temperatures can interact with, or insert into, membranes. These
      findings will help develop the application of responsive polymers in drug
      delivery.

PMID- 22419252
TI  - Metastasis: multitasking hyaluronic acid.

PMID- 22419254
TI  - Leukaemia: Adding e for survival.

PMID- 22419255
TI  - Tumour immunology: dendritic cell switch.

PMID- 22419253
TI  - The immune contexture in human tumours: impact on clinical outcome.
AB  - Tumours grow within an intricate network of epithelial cells, vascular and
      lymphatic vessels, cytokines and chemokines, and infiltrating immune cells.
      Different types of infiltrating immune cells have different effects on tumour
      progression, which can vary according to cancer type. In this Opinion article we
      discuss how the context-specific nature of infiltrating immune cells can affect
      the prognosis of patients.

PMID- 22419257
TI  - Cost-effectiveness analysis of FET PET-guided target selection for the diagnosis
      of gliomas.
AB  - PURPOSE: Several diagnostic trials have indicated that the combined use of (18)F
      fluoroethyl-L: -tyrosine (FET) PET and MRI may be superior to MRI alone in
      selecting the biopsy site for the diagnosis of gliomas. We estimated the cost
      effectiveness of the use of amino acid PET compared to MRI alone from the
      perspective of the German statutory health insurance. METHODS: To evaluate the
      incremental cost-effectiveness of the use of amino acid PET, a decision tree
      model was built. The effectiveness of FET PET was determined by the probability
      of a correct diagnosis. Costs were estimated for a baseline scenario and for a
      more expensive scenario in which disease severity was considered. The robustness
      of the results was tested using deterministic and probabilistic sensitivity
      analyses. RESULTS: The combined use of PET and MRI resulted in an increase of
      18.5% in the likelihood of a correct diagnosis. The incremental cost
      effectiveness ratio for one additional correct diagnosis using FET PET was ?6,405
      for the baseline scenario and ?9,114 for the scenario based on higher disease
      severity. The probabilistic sensitivity analysis confirmed the robustness of the
      results. CONCLUSION: The model indicates that the use of amino acid PET may be
      cost-effective in patients with glioma. As a result of several limitations in the
      data used for the model, further studies are needed to confirm the results.

PMID- 22419258
TI  - Comparison of open-flow microperfusion and microdialysis methodologies when
      sampling topically applied fentanyl and benzoic acid in human dermis ex vivo.
AB  - PURPOSE: The purpose of this study is to compare two sampling methods--dermal
      Open-Flow Microperfusion (dOFM) and dermal Microdialysis (dMD) in an
      international joint experiment in a single-laboratory setting. We used human ex
      vivo skin and sampled topically administered Fentanyl and Benzoic Acid. The
      second purpose was to provide guidance to researchers in choosing the most
      efficient method for a given penetrant and give suggestions concerning critical
      choices for successful dermal sampling. METHODS: The dOFM and dMD techniques are
      compared in equal set-ups using three probe-types (one dOFM probe and two dMD
      probe-types) in donor skin (n = 9)--27 probes of each type sampling each
      penetrant in solutions applied in penetrationchambers glued to the skin surface
      over a time range of 20 h. RESULTS: Pharmacokinetic results demonstrated
      concordance between dOFM and dMD sampling technique under the given experimental
      conditions. The methods each had advantages and limitations in technical,
      practical and hands-on comparisons. CONCLUSION: When planning a study of
      cutaneous penetration the advantages and limitations of each probe-type have to
      be considered in relation to the scientific question posed, the physico-chemical
      characteristics of the substance of interest, the choice of experimental setting
      e.g. ex vivo/in vivo and the analytical skills available.

PMID- 22419259
TI  - Attenuation of phosphorylation by deoxycytidine kinase is key to acquired
      gemcitabine resistance in a pancreatic cancer cell line: targeted proteomic and
      metabolomic analyses in PK9 cells.
AB  - PURPOSE: Multiple proteins are involved in activation and inactivation of 2',2'
      difluorodeoxycytidine (gemcitabine, dFdC). We aimed to clarify the mechanism of
      dFdC resistance in a pancreatic cancer cell line by applying a combination of
      targeted proteomic and metabolomic analyses. METHODS: Twenty-five enzyme and
      transporter proteins and 6 metabolites were quantified in sensitive and resistant
      pancreatic cancer cell lines, PK9 and RPK9, respectively. RESULTS: The protein
      concentration of deoxycytidine kinase (dCK) in RPK9 cells was less than 0.02-fold
      (2 %) compared with that in PK9 cells, whereas the differences (fold) were within
      a factor of 3 for other proteins. Targeted metabolomic analysis revealed that
      phosphorylated forms of dFdC were reduced to less than 0.2 % in RPK9 cells. The
      extracellular concentration of 2',2'-difluorodeoxyuridine (dFdU), an inactive
      metabolite of dFdC, reached the same level as the initial dFdC concentration in
      RPK9 cells. However, tetrahydrouridine treatment did not increase phosphorylated
      forms of dFdC and did not reverse dFdC resistance in RPK9 cells, though this
      treatment inhibits production of dFdU. CONCLUSIONS: Combining targeted proteomics
      and metabolomics suggests that acquisition of resistance in RPK9 cells is due to
      attenuation of dFdC phosphorylation via suppression of dCK.

PMID- 22419260
TI  - Keratin 8 variants are associated with cryptogenic hepatitis.
AB  - Keratins 8 and 18 (K8 and K18) are the cytoskeletal intermediate filament
      proteins of adult hepatocytes. Murine models indicate that mutations in the K8-
      and K18-encoding genes predispose to liver injury. Moreover, studies showed an
      association of K8/K18 variants with human acute and chronic liver diseases.
      However, only little is known about a putative association of K8/K18 variants
      with cryptogenic hepatitis, a frequent liver disease of enigmatic etiology, often
      necessitating liver transplantation. Therefore, we analyzed whether K8 variants
      associate with cryptogenic hepatitis in a German cohort of patients in comparison
      to control blood bank donors. Genomic DNA isolated from liver biopsies of
      cryptogenic hepatitis patients or peripheral blood of healthy donors was analyzed
      for K8 variants by PCR amplification and direct DNA sequencing. We identified 8
      novel heterozygous or homozygous amino acid-altering K8 variants in 5 of 62
      cryptogenic hepatitis patients (8.1 %) and in none of 67 controls (P = 0.02).
      Previously described K8 variants p.G62C and p.R341H were found at similar
      incidence in cryptogenic hepatitis patients and controls. Hence, they were
      considered as polymorphisms not associated with liver disease progression. In
      conclusion, previously undescribed K8 variants associate with cryptogenic
      hepatitis in a German cohort of patients, possibly predisposing carriers to the
      development of liver disease.

PMID- 22419261
TI  - Optimized algorithm for Sanger sequencing-based EGFR mutation analyses in NSCLC
      biopsies.
AB  - Pulmonary adenocarcinoma patients harboring EGFR mutations can benefit from
      tyrosine kinase inhibitor therapy. Reliable molecular analyses and precise
      pathological reporting of the EGFR mutational status are factors essential for
      patient treatment and outcome. More than 70 % of all EGFR mutation analyses are
      performed on non-small cell lung cancer (NSCLC) biopsies. However, biopsies may
      not be sufficient for mutation analysis due to low tumor content and admixture
      with non-neoplastic cells. To define the minimal concentration of tumor cells
      required for reliable EGFR mutational diagnostics by Sanger sequencing and to
      develop an algorithm for routine diagnostics on biopsy material, we determined
      total numbers of tumor and non-tumor cells, calculated the tumor cell
      concentration and serially diluted DNA from EGFR-mutated NSCLC by adding DNA of
      non-tumor cells from the same section. A counted tumor cell concentration of 30
      %, which refers to a histologically estimated concentration of 40 %, is necessary
      for reliable detection of all mutations. Based on these data, we developed an
      algorithm for evidence-based EGFR mutation analysis by Sanger sequencing in
      biopsy specimens, which was subsequently applied to 461 diagnostic cases.
      Optimized diagnostic testing results in 80 % reliable EGFR mutation analyses of
      biopsy specimens, while in 20 % of cases re-biopsies had to be recommended.

PMID- 22419262
TI  - Overactive bladder symptoms and voiding dysfunction in neurologically normal
      women.
AB  - AIMS: To understand mechanisms underlying overactive bladder (OAB) and voiding
      dysfunction (VD) in neurologically normal women. METHODS: Review of MEDLINE from
      (1982) to (2011) using defined search terms, and manual analysis. Only articles
      published in English were included. RESULTS: One in five women report moderate to
      severe lower urinary tract symptoms (LUTS). Whilst VD is more common in men,
      women report a higher rate of storage symptoms or post-micturition symptoms. Post
      void residual (PVR) volume measurements are vital in the assessment of women with
      LUTS and patients with VD without stress incontinence (SUI) are likely to have an
      elevated PVR (82%). Bladder outlet obstruction (BOO) also causes VD in women and
      can be alleviated by surgery or alpha-blocker therapy, although OAB symptoms
      typically remain. Surgical repair for SUI can result in temporary VD in the
      minority of patients, highlighting the complex interplay that is emerging in the
      urethral bladder functioning complex in women. CONCLUSIONS: Women with impaired
      bladder emptying present with a wide range of LUTS, and PVR measurement is
      essential for diagnosis. OAB and VD can clearly coexist and accurate diagnosis of
      underlying pathophysiology is required. Recommendations for clinical practice and
      research are provided including: investigation of VD in women with OAB;
      evaluation of PVR values to determine appropriate therapy and identification of
      BOO. There is clearly a need for further research into the impact of alpha
      blockers in women with VD as well as an evaluation of PVR changes in women with
      OAB before and after antimuscarinic therapy.

PMID- 22419263
TI  - Efficacy of intra-articular tranexamic acid in blood loss reduction following
      primary unilateral total knee arthroplasty.
AB  - PURPOSE: The surgical stress of total knee arthroplasty (TKA) procedure and the
      application of intra-operative pneumatic thigh tourniquet increases local
      fibrinolytic activity, which contributes significantly to post-operative blood
      loss. Tranexamic acid, an antifibrinolytic drug, is commonly used to control post
      operative blood loss. The recommended mode of administration of tranexamic acid
      is either oral or intravenous. However, the mechanism of action of the tranexamic
      acid points towards the possible effectiveness it may have following local/intra
      articular application. This prospective, double-blinded, randomized preliminary
      study evaluated the efficacy of intra-articular tranexamic acid in reducing TKA
      associated post-operative blood loss. METHODS: Fifty consenting patients with
      osteoarthritis of the knee scheduled for primary unilateral cemented-TKA were
      randomly allocated to one of the two groups: Tranexamic Acid (TA) group (n = 25,
      500 mg/5 ml tranexamic acid) and the control group (n = 25, 5 ml 0.9% saline).
      The drug and control solution were administered intra-articularly through the
      drain tube immediately after the wound closure. Parameters related to blood loss
      (drop in haemoglobin, haematocrit differential) and the drain output [volume
      (ml)] were compared between the two groups. RESULTS: On a comparative basis, TA
      group obtained significant reduction in the drain output [95% CI: 360.41-539.59,
      p < 0.001] at 48 h post-operatively. Even though the control group received
      sixfold more blood transfusion than TA-group, it showed a greater drop in
      haemoglobin and haematocrit (p < 0.05). CONCLUSIONS: Local application of
      tranexamic acid seems to be effective in reducing post-TKA blood loss as well as
      blood transfusion requirements. LEVEL OF EVIDENCE: Therapeutic study, Level II.

PMID- 22419264
TI  - Comparison of the minimally invasive and standard medial parapatellar approaches
      for primary total knee arthroplasty.
AB  - PURPOSE: The minimally invasive surgical (MIS) approach has been popularised as
      an alternative to the standard medial parapatellar approach (MPP) in total knee
      arthroplasty (TKA). Advocates of this technique suggest earlier functional
      recovery due to less injury to the surrounding tissues. Potential disadvantages
      however may include reduced overall exposure, component malalignment and damage
      to neurovascular structures. METHODS: A systematic review and meta-analysis of
      randomised and quasi-randomised trials were conducted to compare the MIS and MPP
      approaches in primary TKA. Methodological features were rated independently by
      two reviewers. RESULTS: Seventeen studies were included involving 733 patients
      with mean age of 69 (SD +/- 2.8) in the MIS group and 692 patients with mean age
      of 68.6 (SD +/- 3.1) in the MPP group. Using a MIS approach led to significant
      increase in flexion within the first week after a TKA (mean difference (MD) of
      9.9 degrees  (95% confidence interval (CI) 8.2-11.6, P < 0.01)). However, this
      effect was not sustainable at further follow-ups of >= 3 months. MIS showed a
      significantly increased risk of developing intraoperative complications with a
      risk ratio (RR) of 7.6 (95% CI 3.5-16.3, P < 0.01). CONCLUSION: MIS results in
      superior function in the immediate postoperative period after a primary TKA but
      is also associated with increased rates of intraoperative complications, and
      therefore, a standard approach that allows adequate exposure and avoids tension
      to the wound edges would be more appropriate to prevent such complications. LEVEL
      OF EVIDENCE: Therapeutic study, Level I.

PMID- 22419265
TI  - Fixed versus mobile weight-bearing prosthesis in total knee arthroplasty.
AB  - PURPOSE: This study was designed to compare clinical, radiological, and general
      health results of two prostheses (mobile vs. fixed weight-bearing devices) that
      are used in total knee arthroplasty with a 5-year follow-up. METHODS: This
      randomized controlled study was conducted from 2004 to 2010 in the Department of
      Orthopedic Surgery at two university hospitals in Isfahan, Iran. Three hundred
      patients with expected primary total knee arthroplasty (TKA) without severe
      deformity (a fixed varus or valgus deformity greater than 20 degrees ) received
      fixed weight-bearing (n = 150) or mobile weight-bearing (n = 150) devices.
      Clinical, radiological, and quality of life outcomes were compared between the
      two groups at six-month intervals for the first year, after which the comparisons
      were made annually for the next 4 years. RESULTS: Both groups had similar
      baseline characteristics. Although there was significant improvement in both
      groups, there was no significant difference between the groups with regard to the
      means of the Knee Society Scores, which were 92 (SD: 12.1) for the fixed weight
      bearing device and 93 (SD: 14.2) for the mobile weight-bearing device (n.s.) at
      the final follow-up point. Radiographs showed that there was no significant
      difference in prosthetic alignment and no evidence of loosening. After TKA, the
      SF-36 score increased in both groups, but there was no statistical difference
      between the groups in quality of life at the final follow-up (62 (12.2) vs. 64
      (14.3), n.s.). There was no revision after 5 years. CONCLUSIONS: In terms of
      clinical, radiological or general health outcomes for people who underwent TKA,
      the results of this study showed no clear advantage of mobile weight-bearing over
      the fixed weight-bearing prosthesis at the five-year follow-up. LEVEL OF
      EVIDENCE: I.

PMID- 22419266
TI  - Biomechanical comparison of different graft positions for single-bundle anterior
      cruciate ligament reconstruction.
AB  - PURPOSE: Recent reports have highlighted the importance of an anatomic tunnel
      placement for anterior cruciate ligament (ACL) reconstruction. The purpose of
      this study was to compare the effect of different tunnel positions for single
      bundle ACL reconstruction on knee biomechanics. METHODS: Sixteen fresh-frozen
      cadaver knees were used. In one group (n = 8), the following techniques were used
      for knee surgery: (1) anteromedial (AM) bundle reconstruction (AM-AM), (2)
      posterolateral (PL) bundle reconstruction (PL-PL) and (3) conventional vertical
      single-bundle reconstruction (PL-high AM). In the other group (n = 8), anatomic
      mid-position single-bundle reconstruction (MID-MID) was performed. A
      robotic/universal force-moment sensor system was used to test the knees. An
      anterior load of 89 N was applied for anterior tibial translation (ATT) at 0
      degrees , 15 degrees , 30 degrees  and 60 degrees  of knee flexion. Subsequently,
      a combined rotatory load (5 Nm internal rotation and 7 Nm valgus moment) was
      applied at 0 degrees , 15 degrees , 30 degrees  and 45 degrees  of knee flexion.
      The ATT and in situ forces during the application of the external loads were
      measured. RESULTS: Compared with the intact ACL, all reconstructed knees had a
      higher ATT under anterior load at all flexion angles and a lower in situ force
      during the anterior load at 60 degrees  of knee flexion. In the case of combined
      rotatory loading, the highest ATT was achieved with PL-high AM; the in situ force
      was most closely restored with MIDMID, and the in situ force was the highest AM
      AM at each knee flexion angle. CONCLUSION: Among the techniques, AM-AM afforded
      the highest in situ force and the least ATT.

PMID- 22419267
TI  - Cryopreservation with glycerol improves the in vitro biomechanical
      characteristics of human patellar tendon allografts.
AB  - PURPOSE: To evaluate the in vitro biomechanical characteristics of patellar
      tendon ligaments (BTB) when stored as fresh frozen or as glycerol cryopreserved
      allografts. METHODS: Seventy patellar tendons were harvested from 35 cadaveric
      human donors and randomly assigned into seven groups. Grafts in group FRESH were
      mechanically tested within 2 h of harvesting. FROZ-3, FROZ-6, and FROZ-9 were
      deep-frozen to -80  degrees C for 3, 6, and 9 months, respectively. Grafts in
      groups CRYO-3, CRYO-6, and CRYO-9 were initially incubated with 10% glycerol in a
      phosphate-buffered saline for 1 h and then stored in glycerol solution (10%
      glycerol in PBS) at -80  degrees C for 3, 6, and 9 months, respectively. Grafts
      were mechanically tested with two cycling modes (50-250  degrees N and 150-500 
      degrees N) and then loaded to failure. RESULTS: Cryopreserved grafts demonstrated
      more consistent results and expressed lower elongation rates after both cycling
      loading protocols compared to their frozen counterparts at all storage times.
      During load-to-failure analysis, ultimate stiffness levels were predominantly
      higher (23.9-61.5%) in cryopreserved grafts compared with frozen grafts, and
      ultimate stress levels were 26% (13.3-47.7%) higher, regardless of the storage
      time. Moreover, cryopreserved grafts revealed similar ultimate elongation and
      uniformly higher ultimate stiffness and ultimate stress levels compared to fresh
      grafts. CONCLUSION: The results of this in vitro study demonstrated superior
      mechanical properties of cryopreserved grafts compared to frozen grafts within a
      preservation period of 9 months. Cryopreservation with glycerol solution might be
      used to further improve the quality of preserved soft-tissue allografts.

PMID- 22419269
TI  - Mechanism for the amorphisation of diamond.
AB  - The breakdown of the diamond lattice is explored by ion implantation and
      molecular dynamics simulations. We show that lattice breakdown is strain-driven,
      rather than damage-driven, and that the lattice persists until 16% of the atoms
      have been removed from their lattice sites. The figure shows the transition
      between amorphous carbon and diamond, with the interfaces highlighted with dashed
      lines.

PMID- 22419268
TI  - Morin protects heart from beta-adrenergic-stimulated myocardial infarction: an
      electrocardiographic, biochemical, and histological study in rats.
AB  - In recent years, polyphenols have attracted considerable attention as agents that
      protect cells or molecules from oxidative myocardial injury. The aim of the study
      was to prove the cardioprotective benefits of the flavonoid morin in
      isoproterenol-induced myocardial infarcted rats. Male Wistar rats are treated
      orally with morin (10 and 20 mg/kg) daily for a period of 21 days. After 21 days
      of pretreatment, isoproterenol (100 mg/kg) was injected subcutaneously to rats at
      an interval of 24 h for 2 days to induce myocardial infarction.
      Electrocardiographical abnormalities and biomarkers were measured in normal and
      experimental rats. Isoproterenol-induced myocardial infarcted rats showed
      significant (p<0.05) increase in the levels of cardiac markers. Pretreatment with
      morin regulated the abnormalities in electrocardiograph and biomarkers. The lipid
      peroxidation products were increased and indicated the increased lipid
      peroxidation in isoproterenol-induced myocardial infarcted rats. The rats
      pretreated with morin significantly reduced lipid peroxidation. The altered lipid
      metabolism was observed in isoproterenol-induced myocardial infarcted rats and in
      pretreatment with morin-regulated lipid metabolism. Histopathological study
      evidenced that the pretreatment with morin inhibited myocardial damage. The
      results of this study proved the protective effect of morin as pretreatment and
      are rational to understand the beneficial effects of morin on cardioprotection
      against myocardial injury. Based on the results, the cardioprotective ability of
      morin on human beings can be studied in the future.

PMID- 22419270
TI  - Chemical analysis and acetylcholinesterase inhibitory effect of anthocyanin-rich
      red leaf tea (cv. Sunrouge).
AB  - BACKGROUND: The purpose of this study was to evaluate the effects of leaf order
      or crop season on anthocyanins and other chemicals in the anthocyanin-rich tea
      cultivar 'Sunrouge' (Camellia sinensis x C. taliensis) by using high-performance
      liquid chromatography, and to study the effect of 'Sunrouge' extract on
      acetylcholinesterase (AChE) activity in human neuroblastoma SK-N-SH cells.
      RESULTS: The total anthocyanin content was higher in the third (3.09 mg g-1) than
      in the second (2.24 mg g-1) or first crop season (1.79 mg g-1). The amount of
      anthocyanins contained in the stem was high (1.61 mg g-1). In the third crop
      season, the concentrations of delphinidin-3-O-beta-D-(6-(E)-p
      coumaroyl)galactopyranoside (DCGa), cyanidin-3-O-beta-D-(6-(E)-p
      coumaroyl)galactopyranoside, delphinidin-3-O-beta-D-galactopyranoside,
      delphinidin-3-O-beta-D-(6-O-(Z)-p-coumaroyl)galactopyranoside, cyanidin-3-O-beta
      D-galactoside, and delphinidin-3-O-beta-D-glucoside were 1.57 mg g-1, 0.52 mg g
      1, 0.40 mg g-1, 0.22 mg g-1, 0.14 mg g-1, and 0.11 mg g-1, respectively. DCGa
      accounted for about 50% of the anthocyanins present. The suppressive effect of
      'Sunrouge' water extract on AChE activity in human neuroblastoma SK-N-SH cells
      was the strongest among the three tea cultivars ('Sunrouge', 'Yabukita' and
      'Benifuuki'). CONCLUSION: These results suggested that 'Sunrouge' might protect
      humans from humans from AChE-related diseases by suppressing AChE activity. To
      obtain sufficient amounts of anthocyanins, catechins and/or caffeine for a
      functional food material, 'Sunrouge' from the third crop season should be used.

PMID- 22419271
TI  - Catalytically active single-atom sites fabricated from silver particles.

PMID- 22419272
TI  - Dynamic Nuclear Polarization in the solid state: a transition between the cross
      effect and the solid effect.
AB  - Proton Dynamic Nuclear Polarization (DNP) experiments were conducted on a 3.4 T
      homebuilt hybrid pulsed-EPR-NMR spectrometer, on static samples containing 10 mM
      or 40 mM TEMPOL in frozen glassy solutions of DMSO/water. During DNP experiments
      proton-NMR signals are enhanced with the help of microwave (MW) irradiation on or
      close to the Electron Paramagnetic Resonance (EPR) spectrum of the free radicals
      in the sample, transferring polarization from the free electrons to the nuclei.
      In the solid state a distinction is made between three DNP enhancement
      mechanisms: the Solid Effect (SE), the Cross Effect (CE) and Thermal Mixing (TM).
      In an effort to determine the dominant DNP mechanisms responsible for the
      enhancement of the nuclear signals, electron and nuclear spin-lattice relaxation
      rates, enhancement buildup times and microwave (MW) swept DNP spectra were
      measured as a function of temperature and MW irradiation strength. We observed
      lineshape variations of the DNP spectra that indicated changes in the relative
      contributions of SE-DNP and CE-DNP with temperature and MW power. Using a
      theoretical model describing the SE-DNP and CE-DNP the DNP spectra could be
      analyzed without involving the TM-DNP mechanism and the relative SE-DNP and CE
      DNP contributions to the nuclear enhancement could be determined. From this
      analysis it follows that lowering the temperature beyond 20 K increases the SE
      DNP and decreases the CE-DNP contributions. Possible explanations for this
      behavior are suggested.

PMID- 22419273
TI  - Molecular mapping of high-grade cervical intraepithelial neoplasia shows
      etiological dominance of HPV16.
AB  - Women with high-grade cervical intraepithelial neoplasia (HGCIN) frequently
      present with multiple cervical lesions and multiple concomitant Human
      papillomavirus (HPV) genotype infections. To elucidate HPV genotype attribution
      in different regions on the cervix, we performed molecular mapping of cervical
      disease in women with HGCIN. Thirteen subjects referred to colposcopy for
      abnormal cervical cancer screening results were included. A cervical smear and
      biopsies from 4 different areas on the cervix were collected. HPV genotyping
      using Linear Array (for cytology) or SPF(10)  LiPA(25)  (for histology) were
      performed in 13 smears, 52 whole sections from biopsies and 138 tissue regions
      isolated with laser capture microdissection (LCM). Twelve subjects had a
      diagnosis of CIN3 and one subject had a diagnosis of CIN2 based on the worst
      histology found in 4 biopsies. Eight of the 13 smears (62%) showed multiple
      genotype infections. Four of 13 women (31%) had multiple HPV infections in their
      biopsies. After performing LCM-PCR, only one woman (8%) had two different
      carcinogenic HPV types in morphologically distinct, but colliding HGCIN lesions.
      HPV16 was identified as the causal type in all women with HPV16 in cytology. A
      large proportion of other HPV types found in cervical smears were not detected at
      the tissue level. Using tissue-based genotyping and LCM-PCR analysis, we were
      able to attribute an individual HPV type to each area of CIN lesions. We
      demonstrate that HPV16 is even more etiologically dominant than previously
      thought, based on various genotype attribution models.

PMID- 22419274
TI  - Fibrinogen depleting agents for acute ischaemic stroke.
AB  - BACKGROUND: Fibrinogen depleting agents reduce fibrinogen in blood plasma, reduce
      blood viscosity and hence increase blood flow. This may help remove the blood
      clot blocking the artery and re-establish blood flow to the affected area of the
      brain after an ischaemic stroke. The risk of haemorrhage may be less than with
      thrombolytic agents. This is an update of a Cochrane review first published in
      1997 and last updated in 2003. OBJECTIVES: To assess the effect of fibrinogen
      depleting agents in patients with acute ischaemic stroke. SEARCH METHODS: We
      searched the Cochrane Stroke Group Trials Register (July 2011), the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue
      7), the Chinese Stroke Trials Register (September 2011), MEDLINE (1950 to July
      2011), EMBASE (1980 to July 2011) and Web of Science Conference Proceedings (1990
      to July 2011). In addition, we searched six Chinese databases, four ongoing
      trials registers (July 2011) and relevant reference lists. For previous versions
      of the review, we handsearched journals and contacted researchers in China and
      Japan and relevant drug companies. SELECTION CRITERIA: Randomised trials of
      fibrinogen depleting agents started within 14 days of stroke onset, compared with
      control in patients with definite or possible ischaemic stroke. DATA COLLECTION
      AND ANALYSIS: Two review authors independently selected trials, assessed trial
      quality and extracted the data. We resolved disagreement by discussion. MAIN
      RESULTS: We included eight trials involving 5701 patients. Six trials tested
      ancrod and two trials tested defibrase (patients were treated for less than three
      hours to less than 48 hours). Allocation concealment was adequate in seven
      trials. Fibrinogen depleting agents marginally reduced the proportion of patients
      who were dead or disabled at the end of follow-up (risk ratio (RR) 0.95, 95%
      confidence Interval (CI) 0.90 to 0.99, 2P = 0.02). There was no statistically
      significant difference in death from all causes during the scheduled treatment or
      follow-up period. There were fewer stroke recurrences in the treatment group than
      in the control group (RR 0.67, 95% CI 0.49 to 0.92, 2P = 0.01). However,
      symptomatic intracranial haemorrhage was about twice as common in the treatment
      group compared with the control group (RR 2.42, 95% CI 1.65 to 3.56, 2P <
      0.00001). AUTHORS' CONCLUSIONS: The current evidence is promising but not yet
      sufficiently robust to support the routine use of fibrinogen depleting agents for
      the treatment of acute ischaemic stroke. Further trials are needed to determine
      whether there is worthwhile benefit, and if so, which categories of patients are
      most likely to benefit.

PMID- 22419275
TI  - Inositol for respiratory distress syndrome in preterm infants.
AB  - BACKGROUND: Inositol is an essential nutrient required by human cells in culture
      for growth and survival. Inositol promotes maturation of several components of
      surfactant and may play a critical role in fetal and early neonatal life.
      OBJECTIVES: To assess the effectiveness/safety of supplementary inositol in
      preterm infants with respiratory distress syndrome (RDS) in reducing adverse
      neonatal outcomes. SEARCH METHODS: The Cochrane Central Register of Controlled
      Trials (The Cochrane Library), MEDLINE, EMBASE, CINAHL, Clinicaltrials.gov and
      Controlled-trials.com were searched in May, 2011. The reference lists of
      identified randomized controlled trials (RCTs), personal files and Web of Science
      were searched. SELECTION CRITERIA: All RCTs of inositol supplementation to
      preterm infants with a control group that received a placebo or no intervention
      were included. Outcomes of interest were neonatal death, infant death,
      bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP),
      intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and sepsis.
      DATA COLLECTION AND ANALYSIS: Data on neonatal outcomes were abstracted
      independently by the three review authors and any discrepancy was resolved
      through consensus. Outcomes were reported as relative risk (RR), risk difference
      (RD) and number needed to treat to benefit (NNT). MAIN RESULTS: Four published
      and one ongoing randomized controlled trials were identified. Study quality
      varied and interim analyses had occurred in all trial that provided data for the
      outcomes. Neonatal death was found to be significantly reduced [three trials, 355
      neonates, typical RR 0.53 (95% CI 0.31 to 0.91); RD -0.09 (95% CI -0.17 to 
      0.03); NNT 11 (95% CI 6 to 33). Infant deaths were reduced [three trials, 355
      infants, typical RR 0.55 (95% CI 0.40 to 0.77); RD -0.18 (95% CI -0.27 to -0.08);
      NNT 6 (95% CI 4 to 13). ROP, stage >= 3 was significantly reduced [two trials,
      262 infants, typical RR 0.09 (95% CI 0.01 to 0.67); typical RD -0.08 (95% CI 
      0.13 to -0.03); NNT 13 (95% CI 8 to 33)]. IVH grade > II was significantly
      decreased [three trials, 355 infants typical RR 0.53 (95% CI 0.31 to 0.90;
      typical RD -0.09 (95% CI -0.16 to -0.02); NNT 11 (95% CI 6 to 50). Neither sepsis
      nor NEC differed significantly between groups. One ongoing pharmacokinetics study
      of inositol in preterm infants was identified. AUTHORS' CONCLUSIONS: Inositol
      supplementation results in statistically significant and clinically important
      reductions in important short-term adverse neonatal outcomes. A multicenter
      randomized controlled trial of appropriate size is justified to confirm these
      findings.

PMID- 22419276
TI  - Prophylactic versus selective use of surfactant in preventing morbidity and
      mortality in preterm infants.
AB  - BACKGROUND: Surfactant therapy is effective in improving the outcome of very
      preterm infants. Trials have studied a wide variety of surfactant preparations
      used either to prevent or treat respiratory distress syndrome (RDS). In animal
      models, prophylactic surfactant leads to more homogeneous distribution and less
      evidence of lung damage. However, administration requires intubation and
      treatment of infants who will not go on to develop RDS. This is of particular
      concern with the advent of improved approaches to providing continuous distending
      pressure, particularly in the form of nasal continuous positive airway pressure
      (CPAP). OBJECTIVES: To compare the effect of prophylactic surfactant
      administration to surfactant treatment of established RDS in very preterm infants
      at risk of RDS. SEARCH METHODS: We updated the search of the Cochrane Central
      Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, CINAHL,
      and clinical trials.gov register in December 13, 2011. SELECTION CRITERIA:
      Randomized and quasi-randomized controlled trials that compared the effects of
      prophylactic surfactant administration to surfactant treatment of established RDS
      in preterm infants at risk of RDS. DATA COLLECTION AND ANALYSIS: Data regarding
      clinical outcomes were extracted from the reports of the clinical trials by the
      reviewers. Data analysis was done in accordance with the standards of the
      Cochrane Neonatal Review Group. MAIN RESULTS: Eleven studies were identified that
      met inclusion criteria [nine without routine application of continuous positive
      air way pressure (CPAP) in the selective treatment group; two with routine
      application of CPAP in the selective treatment group]The meta-analysis of studies
      conducted prior to the routine application of CPAP demonstrated a decrease in the
      risk of air leak and neonatal mortality associated with prophylactic
      administration of surfactant. However, the analyses of studies that allowed for
      routine stabilization on CPAP demonstrated a decrease in the risk of chronic lung
      disease or death in infants stabilized on CPAP. When all studies were evaluated
      together, the benefits of prophylactic surfactant could no longer be
      demonstrated. AUTHORS' CONCLUSIONS: Although the early trials of prophylactic
      surfactant administration to infants judged to be at risk of developing RDS
      compared to selective use of surfactant in infants with established RDS
      demonstrated a decreased risk of air leak and mortality, recent large trials that
      reflect current practice (including greater utilization of maternal steroids and
      routine post delivery stabilization on CPAP) do not support these differences and
      demonstrate less risk of chronic lung disease or death when using early
      stabilization on CPAP with selective surfactant administration to infants
      requiring intubation.

PMID- 22419277
TI  - Mechanical methods for induction of labour.
AB  - BACKGROUND: Mechanical methods were the first methods developed to ripen the
      cervix and induce labour. During recent decades they have been substituted by
      pharmacological methods. Potential advantages of mechanical methods, compared
      with pharmacological methods, may include simplicity of preservation, lower cost
      and reduction of the side effects. OBJECTIVES: To determine the effects of
      mechanical methods for third trimester cervical ripening or induction of labour
      in comparison with placebo/no treatment, prostaglandins (vaginal and
      intracervical prostaglandin E2 (PGE2), misoprostol) and oxytocin. SEARCH METHODS:
      We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30
      April 2011) and bibliographies of relevant papers. We updated this search on 16
      January 2012 and added the results to the awaiting classification section of the
      review. SELECTION CRITERIA: Clinical trials comparing mechanical methods used for
      third trimester cervical ripening or labour induction with methods listed above
      it on a predefined list of methods of labour. A comparison with amniotomy will be
      added, should this comparison be made in future trials.Different types of
      intervention have been considered as mechanical methods: (1) introduction of
      laminaria tents, or their synthetic equivalent (Dilapan), into the cervical
      canal; (2) the introduction of a catheter through the cervix into the extra
      amniotic space, with or without traction; (3) use of a catheter to inject
      fluidsin the extra-amniotic spaceIn addition, we made other comparisons: (1)
      specific mechanical methods (balloon catheter and laminaria tents) compared with
      any prostaglandins or with oxytocin; (2) addition of prostaglandins or oxytocin
      to mechanical methods compared with prostaglandins alone. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed trials for inclusion and
      assessed risk of bias. Two review authors independently extracted data. MAIN
      RESULTS: For this update we have included a further 27 studies. The review
      includes 71 randomised controlled trials (total of 9722 women), ranging from 39
      to 588 women per study. Most studies reported on caesarean section, all other
      outcomes are based on substantially fewer women. Four additional studies are
      ongoing.Mechanical methods versus no treatment: one study (48 woman) reported on
      women who did not achieve vaginal delivery within 24 hours (risk ratio (RR) 0.90;
      95% confidence interval (CI) 0.64 to 1.26). The risk of caesarean section was
      similar between groups (six studies; 416 women, RR 1.00; 95% CI 0.76 to 1.30).
      There were no cases of severe neonatal and maternal morbidity.Mechanical methods
      versus vaginal PGE2 (17 studies;1894 woman): The proportion of women who did not
      achieve vaginal delivery within 24 hours was not significantly different (three
      studies; 586 women RR 1.72; 95% CI 0.90 to 3.27); however, for the subgroup of
      multiparous women the risk of not achieving delivery within 24 hours was higher
      (one study; 147 women RR 4.38, 95% CI 1.74 to 10.98), with no increase in
      caesarean sections (RR 1.19, 95% CI 0.62-2.29). Compared with intracervical PGE2
      (14 studies;1784 women and misoprostol there was no significant difference in the
      proportion of women not achieving vaginal delivery within 24 hours.Mechanical
      methods reduced the risk of hyperstimulation with fetal heart rate changes when
      compared with vaginal prostaglandins: vaginal PGE2 (eight studies; 1203 women, RR
      0.16; 95% CI 0.06 to 0.39) and misoprostol (3% versus 9%) (nine studies; 1615
      women, RR 0.37; 95% CI 0.25 to 0.54). Risk of caesarean section between
      mechanical methods and prostaglandins was comparable. Serious neonatal and
      maternal morbidity were infrequently reported and did not differ between the
      groups.Mechanical methods compared with induction with oxytocin (reduced the risk
      of caesarean section (five studies; 398 women, RR 0.62; 95% CI 0.42 to 0.90). The
      likelihood of vaginal delivery within 24 hours was not reported. Hyperstimulation
      with fetal heart rate changes was reported in one study (200 participants), and
      did not differ. There were no reported cases of severe maternal or neonatal
      morbidity. AUTHORS' CONCLUSIONS: Induction of labour using mechanical methods
      results in similar caesarean section rates as prostaglandins, for a lower risk of
      hyperstimulation. Mechanical methods do not increase the overall number of women
      not delivered within 24 hours, however the proportion of multiparous women who
      did not achieve vaginal delivery within 24 hours was higher when compared with
      vaginal PGE2. Compared with oxytocin, mechanical methods reduce the risk of
      caesarean section.

PMID- 22419278
TI  - Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND).
AB  - BACKGROUND: Riluzole is approved for the treatment of amyotrophic lateral
      sclerosis in most countries. Questions persist about its clinical utility because
      of high cost and modest efficacy. OBJECTIVES: To examine the efficacy of riluzole
      in prolonging survival and in delaying the use of surrogates (tracheostomy and
      mechanical ventilation) to sustain survival, and to assess the effect of riluzole
      upon functional health. SEARCH METHODS: We searched the Cochrane Neuromuscular
      Disease Group Specialized Register (20 April 2011), the Cochrane Central Register
      of Controlled Trials (CENTRAL) (2011, Issue 2), MEDLINE (1966 to April 2011),
      EMBASE (1980 to May 2011) and made enquiries of authors of trials, Aventis
      (manufacturer of riluzole) and other experts in the field. SELECTION CRITERIA:
      Types of studies: randomized controlled trials TYPES OF PARTICIPANTS: adults with
      a diagnosis of amyotrophic lateral sclerosis Types of interventions: treatment
      with riluzole or placebo Types of outcome measures: Primary: pooled hazard ratio
      of tracheostomy-free survival over all time points with riluzole 100 mg.
      Secondary: per cent mortality with riluzole 50 mg, 100 mg and 200 mg; neurologic
      function, muscle strength and adverse events. DATA COLLECTION AND ANALYSIS: One
      author performed data extraction and two other authors checked them. One author
      checked the data and entered them into the computer. The other authors verified
      the data entry. We obtained missing data from the trial authors whenever
      possible. MAIN RESULTS: The four trials examining tracheostomy-free survival
      included a total of 974 riluzole-treated patients and 503 placebo-treated
      patients. No new randomized controlled trials were found when we updated the
      searches for this update in 2011. The methodological quality was acceptable and
      three trials were easily comparable, although one trial (169 participants)
      included older patients in more advanced stages of amyotrophic lateral sclerosis
      and one (195 participants) had multiple primary endpoints. Riluzole 100 mg per
      day provided a benefit for the homogeneous group of patients in the first two
      trials (hazard ratio (HR) 0.80, 95% confidence internal (CI) 0.64 to 0.99, P=
      0.042) and there was no evidence of heterogeneity (P = 0.33). When the third
      trial (which included older and more seriously affected patients) was added,
      there was evidence of heterogeneity (P < 0.0001) and the overall treatment effect
      was reduced but still significant (HR 0.84, 95% CI 0.698 to 0.997, P= 0.046).
      This represented a 9% gain in the probability of surviving one year (49% in the
      placebo and 58% in the riluzole group), and increased median survival from 11.8
      to 14.8 months. There was a small beneficial effect on both bulbar and limb
      function, but not on muscle strength. A three-fold increase in serum alanine
      transferase was more frequent in riluzole-treated patients than controls (mean
      difference 2.62, 95% CI 1.59 to 4.31). AUTHORS' CONCLUSIONS: Riluzole 100 mg
      daily is reasonably safe and probably prolongs median survival by about two to
      three months in patients with amyotrophic lateral sclerosis.

PMID- 22419279
TI  - Glutamine supplementation to prevent morbidity and mortality in preterm infants.
AB  - BACKGROUND: Glutamine is a conditionally essential amino acid. Endogenous
      biosynthesis may be insufficient for tissue needs in states of metabolic stress.
      Evidence exists that glutamine supplementation improves clinical outcomes in
      critically ill adults. It has been suggested that glutamine supplementation may
      also benefit preterm infants. OBJECTIVES: To determine the effects of glutamine
      supplementation on mortality and morbidity in preterm infants. SEARCH METHODS: We
      used the standard search strategy of the Cochrane Neonatal Review Group. This
      included searches of the Cochrane Central Register of Controlled Trials (The
      Cochrane Library, 2011, Issue 4), MEDLINE, EMBASE and CINAHL (to November 2011),
      conference proceedings and previous reviews. SELECTION CRITERIA: Randomised or
      quasi-randomised controlled trials that compared glutamine supplementation versus
      no glutamine supplementation in preterm infants at any time from birth to
      discharge from hospital. DATA COLLECTION AND ANALYSIS: We extracted data using
      the standard methods of the Cochrane Neonatal Review Group, with separate
      evaluation of trial quality and data extraction by two review authors. We
      synthesised data using a fixed-effect model and reported typical relative risk,
      typical risk difference and weighted mean difference. MAIN RESULTS: We identified
      11 randomised controlled trials in which a total of 2771 preterm infants
      participated. Five trials assessed enteral glutamine supplementation and six
      trials assessed parenteral glutamine supplementation. The trials were generally
      of good methodological quality. Meta-analysis did not detect a statistically
      significant effect of glutamine supplementation on mortality [typical relative
      risk 0.98 (95% confidence interval 0.80 to 1.18); risk difference 0.00 (95%
      confidence interval -0.03 to 0.02)] or major neonatal morbidities including the
      incidence of invasive infection or necrotising enterocolitis. Two trials that
      assessed neurodevelopmental outcomes at 18 to 24 months did not find any
      statistically significant differences in various assessments. AUTHORS'
      CONCLUSIONS: The available trial data do not provide evidence that glutamine
      supplementation confers important benefits for preterm infants.

PMID- 22419280
TI  - Acellular vaccines for preventing whooping cough in children.
AB  - BACKGROUND: Routine use of whole-cell pertussis (wP) vaccines was suspended in
      some countries in the 1970s and 1980s because of concerns about adverse effects.
      Following such action, there was a resurgence of whooping cough. Acellular
      pertussis (aP) vaccines, containing purified or recombinant Bordetella pertussis
      (B. pertussis) antigens, were developed in the hope that they would be as
      effective, but less reactogenic than the whole-cell vaccines. OBJECTIVES: To
      assess the efficacy and safety of acellular pertussis vaccines in children.
      SEARCH METHODS: We searched the Cochrane Register of Controlled Trials (CENTRAL)
      (The Cochrane Library 2011, Issue 4) which contains the Cochrane Acute
      Respiratory Infections Group's Specialised Register, MEDLINE (1950 to December
      week 4, 2011), EMBASE (1974 to January 2012), Biosis Previews (2009 to January
      2012), and CINAHL (2009 to January 2012). SELECTION CRITERIA: We selected double
      blind randomised efficacy and safety trials of aP vaccines in children up to six
      years old, with active follow-up of participants and laboratory verification of
      pertussis cases. DATA COLLECTION AND ANALYSIS: Two review authors independently
      extracted data and assessed the risk of bias in the studies. Differences in trial
      design precluded a meta-analysis of the efficacy data. We pooled the safety data
      from individual trials using a random-effects meta-analysis model. MAIN RESULTS:
      We included six efficacy trials with a total of 46,283 participants and 52 safety
      trials with a total of 136,541 participants. Most of the safety trials did not
      report the methods for random sequence generation, allocation concealment and
      blinding, which made it difficult to assess the risk of bias in the studies. The
      efficacy of multi-component (>= three) vaccines varied from 84% to 85% in
      preventing typical whooping cough (characterised by 21 or more consecutive days
      of paroxysmal cough with confirmation of B. pertussis infection by culture,
      appropriate serology or contact with a household member who has culture-confirmed
      pertussis), and from 71% to 78% in preventing mild pertussis disease
      (characterised by seven or more consecutive days of cough with confirmation of B.
      pertussis infection by culture or appropriate serology). In contrast, the
      efficacy of one- and two-component vaccines varied from 59% to 75% against
      typical whooping cough and from 13% to 54% against mild pertussis disease. Multi
      component acellular vaccines are more effective than low-efficacy whole-cell
      vaccines, but may be less effective than the highest-efficacy whole-cell
      vaccines. Most systemic and local adverse events were significantly less common
      with aP vaccines than with wP vaccines for the primary series as well as for the
      booster dose. AUTHORS' CONCLUSIONS: Multi-component (>= three) aP vaccines are
      effective and show less adverse effects than wP vaccines for the primary series
      as well as for booster doses.

PMID- 22419281
TI  - Surgery for small asymptomatic abdominal aortic aneurysms.
AB  - BACKGROUND: An abdominal aortic aneurysm (AAA) is an abnormal ballooning of the
      major abdominal artery. Some AAAs present as emergencies and require surgery;
      others remain asymptomatic. Treatment of asymptomatic AAAs depends on many
      factors but an important one is size of the aneurysm, as risk of rupture
      increases with aneurysm size. Large asymptomatic AAAs (> 5.5 cm in diameter) are
      usually operated on; very small AAAs (< 4.0 cm diameter) are monitored with
      ultrasonography. The optimal timing of surgery would benefit from further
      evidence. OBJECTIVES: This review compared long-term survival in patients with
      AAAs of diameter 4.0 to 5.5 cm who received immediate repair versus routine
      ultrasound surveillance. SEARCH METHODS: For this update the Cochrane Peripheral
      Vascular Diseases Group searched their Specialised Register (February 2012) and
      CENTRAL (2012, Issue 1). Reference lists of relevant articles were checked for
      additional studies and the searches were supplemented by handsearches of recent
      conference proceedings and information from experts in the field.  SELECTION
      CRITERIA: Randomised controlled trials in which men and women with asymptomatic
      AAAs of diameter 4.0 to 5.5 cm were randomly allocated to immediate repair or
      imaging-based surveillance at least every six months. Outcomes had to include
      mortality or survival. DATA COLLECTION AND ANALYSIS: Two authors (GF, MAMM)
      abstracted the data, which were cross-checked by the other authors (DJB, JTP).
      Due to the small number of trials, formal tests of heterogeneity and sensitivity
      analyses were not conducted. MAIN RESULTS: Four trials with a combined total of
      3314 patients, the UK Small Aneurysm Trial (UKSAT), the Aneurysm Detection and
      Management (ADAM) trial, the Comparison of Surveillance Versus Aortic
      Endografting for Small Aneurysm Repair (CAESAR), and the Positive Impact of
      Endovascular Options for treating Aneurysms Early (PIVOTAL) fulfilled the
      inclusion criteria. The four trials showed an early survival benefit in the
      surveillance group (due to 30-day operative mortality with surgery) but no
      significant differences in long-term survival (adjusted hazard ratio (HR) 0.88,
      95% confidence interval (CI) 0.75 to 1.02, mean follow up 10 years (UKSAT); HR
      1.21, 95% CI 0.95 to 1.54, mean follow up 4.9 years (ADAM); HR 0.76, 95% CI 0.30
      to 1.93, median follow up 32.4 months (CAESAR); HR 1.01, 95% CI 0.49 to 2.07,
      mean follow up 20 months (PIVOTAL)). The meta analyses of mortality at one year
      (CAESAR and PIVOTAL only) and six years (UKSAT and ADAM only) revealed a non
      significant association (Peto odds ratio at one year 1.15, 95% CI 0.59 to 2.25;
      Peto odds ratio at six years 1.11, 95% CI 0.91 to 1.34).   AUTHORS' CONCLUSIONS:
      The results from the four trials to date demonstrate no advantage to early repair
      (via open or endovascular surgery) for small AAA (4.0 to 5.5 cm) and suggest that
      'best care' for these patients favours surveillance. Furthermore, the more recent
      trials focused on the efficacy of endovascular aneurysm repair and still failed
      to show benefit. Thus, both open and endovascular repair of small AAAs are not
      supported by currently available evidence.

PMID- 22419282
TI  - Ketogenic diet and other dietary treatments for epilepsy.
AB  - BACKGROUND: The ketogenic diet, being high in fat and low in carbohydrates, has
      been suggested to reduce seizure frequency. It is currently used mainly for
      children who continue to have seizures despite treatment with antiepileptic
      drugs. Recently there has been interest in less restrictive ketogenic diets
      including the Atkins diet and the use of these diets has extended into adult
      practice. OBJECTIVES: To review the evidence from randomised controlled trials
      regarding the effects of ketogenic and similar diets. SEARCH METHODS: We searched
      the Cochrane Epilepsy Group's Specialised Register (June 2011), the Cochrane
      Central Register of Controlled Trials (CENTRAL 2011, Issue 2 of 4), MEDLINE (1948
      to May week 4, 2011) and EMBASE (1980 to March 2003). No language restrictions
      were imposed. We checked the reference lists of retrieved studies for additional
      reports of relevant studies. SELECTION CRITERIA: Studies of ketogenic diets and
      similar diets for people with epilepsy. DATA COLLECTION AND ANALYSIS: Three
      review authors independently applied pre-defined criteria to extract data and
      also assessed study quality. MAIN RESULTS: We identified four randomised
      controlled trials which generated five publications.These included Kossoff 2007,
      Bergqvist 2005, Seo 2007, Neal 2008 and Neal 2009. All trials applied the
      intention-to-treat analysis with varied randomisation method. The four studies
      recruited a total of 289 children and adolescents and no adults. Meta-analysis
      could not be conducted due to heterogeneity of the studies. Seven prospective
      studies and four retrospective studies were also identified. AUTHORS'
      CONCLUSIONS: Our review update included data from four new randomised studies of
      the ketogenic diet. Although none were blinded, some were of good quality. These
      studies suggest that in children, the ketogenic diet results in short to medium
      term benefits in seizure control, the effects of which are comparable to modern
      antiepileptic drugs. However, one study of long term outcome reports a high
      attrition rate for the diet. This would suggest that many children find the diet
      difficult to tolerate. The main reasons for drop-outs in the included studies
      included gastrointestinal side effects and dislike for the diet.We found just
      three studies on the use of the diet in adults and none of these were randomised.
      There has been less research involving other diets. We found one randomised study
      of reasonable quality of the Atkins diet. This study showed similar benefits in
      seizure control with a less restrictive diet.For those with medically intractable
      epilepsy or those in whom surgery is unsuitable, a ketogenic diet could improve
      seizure control, but tolerability is poor. One observational study suggested that
      the Atkins diet may have a similar effect on seizure control, but this requires
      more investigation.

PMID- 22419283
TI  - Home versus hospital intravenous antibiotic therapy for cystic fibrosis.
AB  - BACKGROUND: Recurrent endobronchial infection in cystic fibrosis requires
      treatment with intravenous antibiotics for several weeks usually in hospital,
      affecting health costs and quality of life for patients and their families.
      OBJECTIVES: To determine whether home intravenous antibiotic therapy in cystic
      fibrosis is as effective as inpatient intravenous antibiotic therapy and if it is
      preferred by individuals or families or both. SEARCH METHODS: We searched the
      Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising
      references identified from comprehensive electronic database searches and
      handsearches of relevant journals and abstract books of conference
      proceedings.Most recent search of the Group's Trials Register: 01 September 2011.
      SELECTION CRITERIA: Randomized and quasi-randomized controlled studies of
      intravenous antibiotic treatment for adults and children with cystic fibrosis at
      home compared to in hospital. DATA COLLECTION AND ANALYSIS: The authors
      independently selected studies for inclusion in the review, assessed
      methodological quality of each study and extracted data using a standardised
      form. MAIN RESULTS: Eighteen studies were identified by the searches. Only one
      study could be included which reported results from 17 participants aged 10 to 41
      years with an infective exacerbation of Pseudomonas aeruginosa. All their 31
      admissions (18 hospital and 13 at home after two to four days of hospital
      treatment) were analysed as independent events. Outcomes were measured at 0, 10
      and 21 days after initiation of treatment. Home participants underwent fewer
      investigations than hospital participants (P < 0.002) and general activity was
      higher in the home group. No significant differences were found for clinical
      outcomes, adverse events, complications or change of intravenous lines,or time to
      next admission. Home participants received less low-dose home maintenance
      antibiotic.Quality of life measures showed no significant differences for
      dyspnoea and emotional state, but fatigue and mastery were worse for home
      participants, possibly due to a higher general activity and need of support.
      Personal, family, sleeping and eating disruptions were less important for home
      than hospital admissions.Home therapy was cheaper for families and the hospital.
      Indirect costs were not determined. AUTHORS' CONCLUSIONS: Current evidence is
      restricted to a single randomized clinical trial. It suggests that, in the short
      term, home therapy does not harm individuals, entails fewer investigations,
      reduces social disruptions and can be cost-effective. There were both advantages
      and disadvantages in terms of quality of life. The decision to attempt home
      treatment should be based on the individual situation and appropriate local
      resources. More research is urgently required.

PMID- 22419284
TI  - Progestagens and anti-progestagens for pain associated with endometriosis.
AB  - BACKGROUND: Endometriosis is a chronic inflammatory condition defined by the
      presence of glands and stroma outside the uterine cavity. It occurs in 7% to 10%
      of all women of reproductive age and may present as pain or infertility. The
      pelvic pain may be in the form of dysmenorrhoea, dyspareunia or pelvic pain.
      Initially a combination of estrogens and progestagens was used to create a
      pseudopregnancy and alleviate the symptoms associated with endometriosis.
      Progestagens alone or anti-progestagens have been considered as alternatives
      because they are inexpensive and may have a better side effect profile than other
      choices. OBJECTIVES: To determine the effectiveness of both the progestagens and
      anti-progestagens in the treatment of painful symptoms ascribed to the diagnosis
      of endometriosis. SEARCH METHODS: We used the search strategy of the Menstrual
      Disorders and Subfertility Group to identify all publications which described or
      might have described randomised controlled trials (RCTs) of any progestagen or
      any anti-progestagen in the treatment of symptomatic endometriosis. We updated
      the review in 2011. SELECTION CRITERIA: We considered only RCTs which compared
      the use of progestagens and anti-progestagens with other interventions, placebo
      or no treatment for the alleviation of symptomatic endometriosis. DATA COLLECTION
      AND ANALYSIS: We have added six new studies, bringing the total of included
      studies to 13 in the update of this review. The six newly included studies
      evaluated progestagens (comparisons with placebo, danazol, oral or subdermal
      contraceptive, oral contraceptive pill and danazol, gonadotrophin-releasing
      hormone (GnRH) analogue and other drugs). The remaining studies compared the anti
      progestagen gestrinone with danazol, GnRH analogues or itself. MAIN RESULTS: The
      progestagen medroxyprogesterone acetate (100 mg daily) appeared to be more
      effective at reducing all symptoms up to 12 months of follow-up (MD -0.70, 95% CI
      -8.61 to -5.39; P < 0.00001) compared with placebo. There was evidence of
      significantly more cases of acne (six versus one) and oedema (11 versus one) in
      the medroxyprogesterone acetate group compared with placebo. There was no
      evidence of a difference in objective efficacy between dydrogesterone and
      placebo.There was no evidence of a benefit with depot administration of
      progestagens versus other treatments (low dose oral contraceptive or leuprolide
      acetate) for reduced symptoms. The depot progestagen group experienced
      significantly more adverse effects.There was no overall evidence of a benefit of
      oral progestagens over other medical treatment at six months of follow-up for
      self-reported efficacy. Amenorrhoea and bleeding were more frequently reported in
      the progestagen group compared with other treatment groups.There was no evidence
      of a benefit of anti-progestagens (gestrinone) compared with danazol. GnRH
      analogue (leuprorelin) was found to significantly improve dysmenorrhoea compared
      with gestrinone (MD 0.82, 95% CI 0.15 to 1.49; P = 0.02) although it was also
      associated with increased hot flushes (OR 0.20, 95% CI 0.06 to -0.63; P = 0.006).
      AUTHORS' CONCLUSIONS: There is only limited evidence to support the use of
      progestagens and anti-progestagens for pain associated with endometriosis.

PMID- 22419285
TI  - WITHDRAWN: Interventions for treating posterior cruciate ligament injuries of the
      knee in adults.
AB  - BACKGROUND: Injuries of the posterior cruciate ligament (PCL) of the knee
      frequently occur in automobile accidents and sports injuries, although they are
      less frequent overall than injuries of the anterior cruciate ligament (ACL). Some
      patients show significant symptoms and subsequent articular deterioration, while
      others are essentially asymptomatic, maintaining habitual function. Management of
      PCL injuries remains controversial and prognosis can vary widely. Interventions
      extend from non-operative (conservative) procedures to reconstruction of the PCL,
      in the hope that the surgical procedure may have a positive effect in the
      reduction/prevention of future osteoarthritic changes in the knee. OBJECTIVES: To
      determine the effectiveness and safety of surgical and conservative interventions
      for PCL injuries in adults. SEARCH METHODS: We searched the Cochrane Bone, Joint
      and Muscle Trauma Group Specialised Register (April 2004), the Cochrane Central
      Register of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE via
      PubMed (1966 to April 2004), EMBASE (1966 to April 2004), CINAHL (1982 to April
      2004), LILACS (1982 to April 2004), SportsDiscus (1975 to April 2004), and
      reference lists of articles. SELECTION CRITERIA: Randomized or quasi-randomized
      clinical trials comparing various methods of operative and conservative
      interventions, and comparisons with each other for the treatment of PCL injuries.
      DATA COLLECTION AND ANALYSIS: References found with the search strategy were
      evaluated independently by two review authors. MAIN RESULTS: No randomized or
      quasi-randomized controlled studies meeting the selection criteria were
      identified. AUTHORS' CONCLUSIONS: Future research should include randomized
      controlled trials of acute isolated PCL injuries, or PCL injuries when combined
      with other ligament injuries of the knee, treated operatively and conservatively.
      Adequate numbers of patients and an objective methodology for patient evaluation
      must be used in future studies of these interventions to determine the long-term
      results.

PMID- 22419286
TI  - Interventions for asymptomatic retinal breaks and lattice degeneration for
      preventing retinal detachment.
AB  - BACKGROUND: Asymptomatic retinal breaks and lattice degeneration are visible
      lesions that are risk factors for later retinal detachment. Retinal detachments
      occur when fluid in the vitreous cavity passes through tears or holes in the
      retina and separates the retina from the underlying retinal pigment epithelium.
      Creation of an adhesion surrounding retinal breaks and lattice degeneration, with
      laser photocoagulation or cryotherapy, has been recommended as an effective means
      of preventing retinal detachment. This therapy is of value in the management of
      retinal tears associated with the symptoms of flashes and floaters and persistent
      vitreous traction upon the retina in the region of the retinal break, because
      such symptomatic retinal tears are associated with a high rate of progression to
      retinal detachment. Retinal tears and holes unassociated with acute symptoms and
      lattice degeneration are significantly less likely to be the sites of retinal
      breaks that are responsible for later retinal detachment. Nevertheless, treatment
      of these problems is frequently recommended, in spite of the fact that the
      effectiveness of this therapy is unproven. OBJECTIVES: The purpose of this review
      was to evaluate the effectiveness of interventions for asymptomatic retinal
      breaks and lattice degeneration. SEARCH METHODS: We searched CENTRAL (which
      contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane
      Library 2012, Issue 1), MEDLINE (January 1950 to January 2012), EMBASE (January
      1980 to January 2012), the metaRegister of Controlled Trials (mRCT)
      (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the
      WHO International Clinical Trials Registry Platform (ICTRP)
      (www.who.int/ictrp/search/en). There were no date or language restrictions in the
      electronic searches for trials. The electronic databases were last searched on 28
      January 2012. Textbooks regarding retinal detachment and the reference lists of
      relevant reports were reviewed for additional study reports. Experts in the field
      were contacted for details of other published and unpublished studies. SELECTION
      CRITERIA: This review was designed to include randomized controlled trials in
      which one treatment for asymptomatic retinal breaks and lattice degeneration was
      compared to another treatment or to no treatment. DATA COLLECTION AND ANALYSIS:
      Initially one author assessed the search results and collected relevant studies.
      Since no studies met the inclusion criteria, no studies were assessed for
      methodological quality. No data were extracted and no meta-analysis could be
      performed. MAIN RESULTS: No trials were found that met the inclusion criteria for
      this review. AUTHORS' CONCLUSIONS: No conclusions could be reached about the
      effectiveness of surgical interventions to prevent retinal detachment in eyes
      with asymptomatic retinal breaks and/or lattice degeneration. Some current
      recommendations for treatment, based upon a consensus of expert opinion, are
      contradicted by the best available evidence.

PMID- 22419287
TI  - Progesterone for premenstrual syndrome.
AB  - BACKGROUND: About 5% of women experience severe symptoms called premenstrual
      syndrome (PMS), only in the two weeks before their menstrual periods. Treatment
      with progesterone may restore a deficiency, balance menstrual hormone levels or
      reduce effects of falling progesterone levels on the brain or on electrolytes in
      the blood. OBJECTIVES: The objectives were to determine if progesterone has been
      found to be an effective treatment for all or some premenstrual symptoms and if
      adverse events associated with this treatment have been reported. SEARCH METHODS:
      We searched the Cochrane Menstrual Disorders and Subfertility Group's Trials
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE,
      EMBASE and PsycINFO to February 2011. We contacted pharmaceutical companies for
      information about unpublished trials, for the first version of this review.The
      search strings are in Appendix 2. SELECTION CRITERIA: We included randomised
      double-blind, placebo-controlled trials of progesterone on women with PMS
      diagnosed by at least two prospective cycles, without current psychiatric
      disorder. DATA COLLECTION AND ANALYSIS: Two reviewers (BM and OF) extracted data
      independently and decided which trials to include. OF wrote to trial
      investigators for missing data. MAIN RESULTS: From 17 studies, only two met our
      inclusion criteria. Together they had 280 participants aged between 18 and 45
      years. One hundred and fifteen yielded analysable results. Both studies measured
      symptom severity using subjective scales. Differing in design, participants, dose
      of progesterone and how delivered, the studies could not be combined in meta
      analysis.Adverse events which may or may not have been side effects of the
      treatment were described as mild.Both trials had defects. They intended to
      exclude women whose symptoms continued after their periods. When data from
      ineligible women were excluded from analysis in one trial, the other women were
      found to have benefited more from progesterone than placebo. The smaller study
      found no statistically significant difference between oral progesterone,
      vaginally absorbed progesterone and placebo, but reported outcomes incompletely.
      AUTHORS' CONCLUSIONS: The trials did not show that progesterone is an effective
      treatment for PMS nor that it is not. Neither trial distinguished a subgroup of
      women who benefited, nor examined claimed success with high doses.

PMID- 22419288
TI  - Expectant care versus surgical treatment for miscarriage.
AB  - BACKGROUND: Miscarriage is a common complication of early pregnancy that can have
      both medical and psychological consequences such as depression and anxiety. The
      need for routine surgical evacuation with miscarriage has been questioned because
      of potential complications such as cervical trauma, uterine perforation,
      hemorrhage, or infection. OBJECTIVES: To compare the safety and effectiveness of
      expectant management versus surgical treatment for early pregnancy failure.
      SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (9 February 2012), the Cochrane Central Register of Controlled Trials
      (The Cochrane Library 2011, Issue 4 of 4), PubMed (2005 to 11 January 2012),
      POPLINE (inception to 11 January 2012), LILACS (2005 to 11 January 2012) and
      reference lists of retrieved studies. SELECTION CRITERIA: Randomized trials
      comparing expectant care and surgical treatment (vacuum aspiration or dilation
      and curettage) for miscarriage were eligible for inclusion. DATA COLLECTION AND
      ANALYSIS: Two review authors assessed trial quality and extracted data. We
      contacted study authors for additional information. For dichotomous data, we
      calculated the Mantel-Haenszel risk ratio (RR) with 95% confidence interval (CI).
      For continuous data, we computed the mean difference (MD) and 95% CI. We entered
      additional data such as medians into 'Other data' tables. MAIN RESULTS: We
      included seven trials with 1521 participants in this review. The expectant-care
      group was more likely to have an incomplete miscarriage by two weeks (RR 3.98;
      95% CI 2.94 to 5.38) or by six to eight weeks (RR 2.56; 95% CI 1.15 to 5.69). The
      need for unplanned surgical treatment was greater for the expectant-care group
      (RR 7.35; 95% CI 5.04 to 10.72). The mean percentage needing surgical management
      in the expectant-care group was 28%, while 4% of the surgical-treatment group
      needed additional surgery. The expectant-care group had more days of bleeding (MD
      1.59; 95% CI 0.74 to 2.45). Further, more of the expectant-care group needed
      transfusion (RR 6.45; 95% CI 1.21 to 34.42). The mean percentage needing blood
      transfusion was 1.4% for expectant care compared with none for surgical
      management. Results were mixed for pain. Diagnosis of infection was similar for
      the two groups (RR 0.63; 95% CI 0.36 to 1.12), as were results for various
      psychological outcomes. Pregnancy data were limited. Costs were lower for the
      expectant-care group (MD -499.10; 95% CI -613.04 to -385.16; in UK pounds
      sterling). AUTHORS' CONCLUSIONS: Expectant management led to a higher risk of
      incomplete miscarriage, need for unplanned (or additional) surgical emptying of
      the uterus, bleeding and need for transfusion. Risk of infection and
      psychological outcomes were similar for both groups. Costs were lower for
      expectant management. Given the lack of clear superiority of either approach, the
      woman's preference should be important in decision making. Pharmacological
      ('medical') management has added choices for women and their clinicians and has
      been examined in other reviews.

PMID- 22419289
TI  - Sedation of children undergoing dental treatment.
AB  - BACKGROUND: Children's fear about dental treatment may lead to behaviour
      management problems for the dentist, which can be a barrier to the successful
      dental treatment of children. Sedation can be used to relieve anxiety and manage
      behaviour in children undergoing dental treatment. There is a need to determine
      from published research which agents, dosages and regimens are effective.
      OBJECTIVES: To evaluate the efficacy and relative efficacy of conscious sedation
      agents and dosages for behaviour management in paediatric dentistry. SEARCH
      METHODS: Electronic searches of MEDLINE, EMBASE, Cochrane Central Register of
      Controlled Trials, Dissertation Abstracts, SIGLE, the World Wide Web (Google) and
      the Community of Science Database were conducted for relevant trials and
      references up to 4th August 2011. Reference lists from relevant articles were
      scanned and the authors contacted to identify trials and obtain additional
      information. There were no language restrictions. Trials pre-1966 were not
      searched. SELECTION CRITERIA: Studies were selected if they met the following
      criteria: randomised controlled trials of conscious sedation comparing two or
      more drugs/techniques/placebo undertaken by the dentist or one of the dental team
      in children up to 16 years of age. Crossover trials were excluded. DATA
      COLLECTION AND ANALYSIS: Information regarding methods, participants,
      interventions, outcome measures and results were independently extracted, in
      duplicate, by two review authors. Where information in trial reports was unclear
      or incomplete authors of trials were contacted. Trials were assessed for risk of
      bias. The Cochrane Collaboration statistical guidelines were followed. MAIN
      RESULTS: Thirty-six studies were included with a total of 2810 participants.
      Thirty trials (83%) were at high risk of bias and six (17%) were at unclear risk
      of bias. There were 28 different sedatives used with or without inhalational
      nitrous oxide. Dosages, mode of administration and time of administration varied
      widely. Trials were grouped into placebo-controlled, dosage and head-to-head
      comparisons. Meta-analysis of the available data was possible for studies
      investigating oral midazolam vs placebo only. There is weak evidence from five
      small clinically heterogeneous trials at high risk of bias, that the use of oral
      midazolam in doses between 0.25 mg/kg to 0.75 mg/kg is associated with more co
      operative behaviour compared to placebo; standardised mean difference (SMD)
      favoured midazolam (SMD 2.98, 95% confidence interval (CI) 1.58 to 4.37, P <
      0.001, I2 = 91%), which translates to an increase of approximately 1.8 points on
      the six-point Houpt behaviour scale. There is very weak evidence from two trials
      which could not be pooled that inhalational nitrous oxide is more effective than
      placebo. AUTHORS' CONCLUSIONS: There is some weak evidence that oral midazolam is
      an effective sedative agent for children undergoing dental treatment. There is
      very weak evidence that nitrous oxide inhalation may also be effective. There is
      a need for further well designed and well reported clinical trials to evaluate
      other potential sedation agents. Further recommendations for future research are
      described and it is suggested that future trials evaluate experimental regimens
      in comparison with oral midazolam or inhaled nitrous oxide.

PMID- 22419290
TI  - Adjuvant radiotherapy for stage I endometrial cancer.
AB  - BACKGROUND: This is an updated version of the original Cochrane review published
      in Issue 2, 2007. The role of radiotherapy (both pelvic external beam
      radiotherapy (EBRT) and vaginal intracavity brachytherapy (VBT)) in stage I
      endometrial cancer following hysterectomy remains controversial. OBJECTIVES: To
      assess the efficacy of adjuvant radiotherapy following surgery for stage I
      endometrial cancer. SEARCH METHODS: We searched The Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Specialised Register to end
      2005 for the original review, and extended the search to January 2012 for the
      update. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that
      compared post-operative adjuvant radiotherapy (either EBRT or VBT, or both)
      versus no radiotherapy or VBT in women with stage I endometrial cancer. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed trials and
      extracted data to a specifically designed data collection form. The primary
      outcome was overall survival. Secondary outcomes were endometrial cancer-related
      deaths, locoregional recurrence and distant recurrence. Meta-analyses were
      performed using Cochrane Review Manager Software 5.1. MAIN RESULTS: We included
      eight trials. Seven trials (3628 women) compared EBRT with no EBRT (or VBT), and
      one trial (645 women) compared VBT with no additional treatment. We considered
      six of the eight trials to be of a high quality. Time-to-event data were not
      available for all trials and all outcomes.EBRT (with or without VBT) compared
      with no EBRT (or VBT alone) for stage I endometrial carcinoma significantly
      reduced locoregional recurrence (time-to-event data: five trials, 2965 women;
      Hazard Ratio (HR) 0.36, 95% Confidence Interval (CI) 0.25 to 0.52; and
      dichotomous data: seven trials, 3628 women; Risk Ratio (RR) 0.33, 95% CI 0.23 to
      0.47). This reduced risk of locoregional recurrence did not translate into
      improved overall survival (time-to-event data: five trials, 2,965 women; HR 0.99,
      95% CI 0.82 to 1.20; and dichotomous data: seven trials, 3628 women; RR 0.98, 95%
      CI 0.83 to 1.15) or improved endometrial cancer-related survival (time-to-event
      data: five trials, 2965 women; HR 0.96, 95% CI 0.72 to 1.28; and dichotomous
      data: seven trials, 3628 women; RR 1.02, 95% CI 0.81 to 1.29) or improved distant
      recurrence rates (dichotomous data: seven trials, 3628 women; RR 1.04, 95% CI
      0.80 to1.35).EBRT did not improve survival outcomes in either the intermediate
      risk or high-risk subgroups, although high-risk data were limited, and a benefit
      of EBRT for high-risk women could not be excluded. In the subgroup of low-risk
      patients (IA/B and grade 1/2), EBRT increased the risk of endometrial carcinoma
      related deaths (including treatment-related deaths) (two trials, 517 women; RR
      2.64, 95% CI 1.05 to 6.66) but there was a lack of data on overall survival. We
      considered the evidence for the low-risk subgroup to be of a low quality.EBRT was
      associated with significantly increased severe acute toxicity (two trials, 1328
      patients, RR 4.68, 95% CI 1.35 to 16.16), increased severe late toxicity (six
      trials, 3501 women; RR 2.58, 95% CI 1.61 to 4.11) and significant reductions in
      quality of life scores and rectal and bladder function more than 10 years after
      randomisation (one trial, 351 women) compared with no EBRT.One trial of VBT
      versus no additional treatment in women with low-risk lesions reported a non
      significant reduction in locoregional recurrence in the VBT group compared with
      the no additional treatment group (RR 0.39, (95% CI 0.14 to 1.09). There were no
      significant differences in survival outcomes in this trial. AUTHORS' CONCLUSIONS:
      EBRT reduces the risk of locoregional recurrence but has no significant impact on
      cancer-related deaths or overall survival. It is associated with significant
      morbidity and a reduction in quality of life, and bladder and rectal function.
      EBRT may have an adverse effect on endometrial cancer survival when used to treat
      uncomplicated low-risk (IA/B grade 1/2) endometrial cancer. There is no
      demonstrable survival advantage from adjuvant EBRT for high-risk stage I
      endometrial cancer, however, the meta-analyses of this subgroup were underpowered
      and also included high-intermediate risk women. Further research is likely to
      have an important impact on our confidence in the estimates of effects and may
      change the estimates. Therefore, whilst there appears to be no survival benefit
      in the routine use of EBRT in women with stage I endometrial cancer, we cannot
      exclude a benefit in high-risk women. VBT is potentially useful in intermediate
      risk and high-risk subgroups but evidence from further RCTs is needed. In
      addition, the definitions of risk should be standardised.

PMID- 22419291
TI  - Postoperative adjuvant chemotherapy in rectal cancer operated for cure.
AB  - BACKGROUND: Colorectal cancer is one of the most common types of cancer in the
      Western world. Apart from surgery - which remains the mainstay of treatment for
      resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5
      fluorouracil (5-FU) based regimens is now the standard treatment in Dukes' C (TNM
      stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes
      but no distant metastases. In contrast, the evidence for recommendations of
      adjuvant therapy in rectal cancer is sparse. In Europe it is generally
      acknowledged that locally advanced rectal tumours receive preoperative (i.e.,
      neoadjuvant) downstaging by radiotherapy (or chemoradiotion), whereas in the US
      postoperative chemoradiotion is considered the treatment of choice in all Dukes'
      C rectal cancers. Overall, no universal consensus exists on the adjuvant
      treatment of surgically resectable rectal carcinoma; moreover, no formal
      systematic review and meta-analysis has been so far performed on this subject.
      OBJECTIVES: We undertook a systematic review of the scientific literature from
      1975 until March 2011 in order to quantitatively summarize the available evidence
      regarding the impact of postoperative adjuvant chemotherapy on the survival of
      patients with surgically resectable rectal cancer. The outcomes of interest were
      overall survival (OS) and disease-free survival (DFS). SEARCH METHODS: CCCG
      standard search strategy in defined databases with the following supplementary
      search. 1. Rect* or colorect* - 2. Cancer or carcinom* or adenocarc* or neoplasm*
      or tumour - 3. Adjuv* - 4. Chemother* - 5. Postoper* SELECTION CRITERIA:
      Randomised controlled trials (RCT) comparing patients undergoing surgery for
      rectal cancer who received no adjuvant chemotherapy with those receiving any
      postoperative chemotherapy regimen. DATA COLLECTION AND ANALYSIS: Two authors
      extracted data and a third author performed an independent search for
      verification. The main outcome measure was the hazard ratio (HR) between the risk
      of event between the treatment arm (adjuvant chemotherapy) and the control arm
      (no adjuvant chemotherapy). The survival data were either entered directly in
      RevMan or extrapolated from Kaplan-Meier plots and then entered in RevMan. Due to
      expected clinical heterogeneity a random effects model was used for creating the
      pooled estimates of treatment efficacy. MAIN RESULTS: A total of 21 eligible RCTs
      were identified and used for meta-analysis purposes. Overall, 16,215 patients
      with colorectal cancer were enrolled, 9,785 being affected with rectal carcinoma.
      Considering patients with rectal cancer only, 4,854 cases were randomized to
      receive potentially curative surgery of the primary tumour plus adjuvant
      chemotherapy and 4,367 to receive surgery plus observation. The mean number of
      patients enrolled was 466 (range: 54-1,243 cases). 11 RCTs had been performed in
      Western countries and 10 in Japan. All trials used fluoropyrimidine-based
      chemotherapy (no modern drugs - such as oxaliplatin, irinotecan or biological
      agents - were tested).Overall survival (OS) data were available in 21 RCTs and
      the data available for meta-analysis regarded 9,221 patients: of these, 4854
      patients were randomized to adjuvant chemotherapy (treatment arm) and 4,367
      patients did not receive adjuvant chemotherapy (control arm). The meta-analysis
      of these RCTs showed a significant reduction in the risk of death (17%) among
      patients undergoing postoperative chemotherapy as compared to those undergoing
      observation (HR=0.83, CI: 0.76-0.91). Between-study heterogeneity was moderate (I
      squared=30%) but significant (P=0.09) at the 10% alpha level.Disease-free
      survival (DFS) data were reported in 20 RCTs, and the data suitable for meta
      analysis included 8,530 patients. Of these, 4,515 patients were randomized to
      postoperative chemotherapy (treatment arm) and 4,015 patients received no
      postoperative chemotherapy (control arm). The meta-analysis of these RCTs showed
      a reduction in the risk of disease recurrence (25%) among patients undergoing
      adjuvant chemotherapy as compared to those undergoing observation (HR=0.75, CI:
      0.68-0.83). Between-study heterogeneity was moderate (I-squared=41%) but
      significant (P=0.03).While analyzing both OS and DFS data, sensitivity analyses
      did not find any difference in treatment effect based on trial sample size or
      geographical region (Western vs Japanese). Available data were insufficient to
      investigate on the effect of adjuvant chemotherapy separately in different TNM
      stages in terms of both OS and DFS. No plausible source of heterogeneity was
      formally identified, although variability in treatment regimens and TNM stages of
      enrolled patients might have played a significant role in the difference of
      reported results. AUTHORS' CONCLUSIONS: The results of this meta-analysis support
      the use of 5-FU based postoperative adjuvant chemotherapy for patients undergoing
      apparently radical surgery for non-metastatic rectal carcinoma. Available data do
      not allow us to define whether the efficacy of this treatment is highest in one
      specific TNM stage. The implementation of modern anti-cancer agents in the
      adjuvant setting is warranted to improve the results shown by this meta-analysis.
      Randomized trials of adjuvant chemotherapy for patients receiving preoperative
      neoadjuvant therapy are also needed in order to define the role of postoperative
      chemotherapy in the multimodal treatment of resectable rectal cancer.

PMID- 22419292
TI  - Central venous access sites for the prevention of venous thrombosis, stenosis and
      infection.
AB  - BACKGROUND: Central venous access (CVA) is widely used. However, its thrombotic,
      stenotic and infectious complications can be life-threatening and involve high
      cost therapy. Research revealed that the risk of catheter-related complications
      varied according to the site of CVA. It would be helpful to find the preferred
      site of insertion to minimize the risk of catheter-related complications. This
      review was originally published in 2007 and was updated in 2011. OBJECTIVES: 1.
      Our primary objective was to establish whether the jugular, subclavian or femoral
      CVA routes resulted in a lower incidence of venous thrombosis, venous stenosis or
      infections related to CVA devices in adult patients.2. Our secondary objective
      was to assess whether the jugular, subclavian or femoral CVA routes influenced
      the incidence of catheter-related mechanical complications in adult patients; and
      the reasons why patients left the studies early. SEARCH METHODS: We searched
      CENTRAL (The Cochrane Library 2011, Issue 9), MEDLINE, CINAHL, EMBASE (from
      inception to September 2011), four Chinese databases (CBM, WANFANG DATA, CAJD,
      VIP Database) (from inception to November 2011), Google Scholar and
      bibliographies of published reviews. The original search was performed in
      December 2006. We also contacted researchers in the field. There were no language
      restrictions. SELECTION CRITERIA: We included randomized controlled trials
      comparing central venous catheter insertion routes. DATA COLLECTION AND ANALYSIS:
      Three authors assessed potentially relevant studies independently. We resolved
      disagreements by discussion. Dichotomous data on catheter-related complications
      were analysed. We calculated relative risks (RR) and their 95% confidence
      intervals (CI) based on a random-effects model. MAIN RESULTS: We identified 5854
      citations from the initial search strategy; 28 references were then identified as
      potentially relevant. Of these, we Included four studies with data from 1513
      participants. We undertook a priori subgroup analysis according to the duration
      of catheterization, short-term (< one month) and long-term (> one month) defined
      according to the Food and Drug Administration (FDA).No randomized controlled
      trial (RCT) was found comparing all three CVA routes and reporting the
      complications of venous stenosis.Regarding internal jugular versus subclavian CVA
      routes, the evidence was moderate and applicable for long-term catheterization in
      cancer patients. Subclavian and internal jugular CVA routes had similar risks for
      catheter-related complications. Regarding femoral versus subclavian CVA routes,
      the evidence was high and applicable for short-term catheterization in critically
      ill patients. Subclavian CVA routes were preferable to femoral CVA routes in
      short-term catheterization because femoral CVA routes were associated with higher
      risks of catheter colonization (14.18% or 19/134 versus 2.21% or 3/136) (n = 270,
      one RCT, RR 6.43, 95% CI 1.95 to 21.21) and thrombotic complications (21.55% or
      25/116 versus 1.87% or 2/107) (n = 223, one RCT, RR 11.53, 95% CI 2.80 to 47.52)
      than with subclavian CVA routes. Regarding femoral versus internal jugular
      routes, the evidence was moderate and applicable for short-term haemodialysis
      catheterization in critically ill patients. No significant differences were found
      between femoral and internal jugular CVA routes in catheter colonization,
      catheter-related bloodstream infection (CRBSI) and thrombotic complications, but
      fewer mechanical complications occurred in femoral CVA routes (4.86% or 18/370
      versus 9.56% or 35/366) (n = 736, one RCT, RR 0.51, 95% CI 0.29 to 0.88).
      AUTHORS' CONCLUSIONS: Subclavian and internal jugular CVA routes have similar
      risks for catheter-related complications in long-term catheterization in cancer
      patients. Subclavian CVA is preferable to femoral CVA in short-term
      catheterization because of lower risks of catheter colonization and thrombotic
      complications. In short-term haemodialysis catheterization, femoral and internal
      jugular CVA routes have similar risks for catheter-related complications except
      internal jugular CVA routes are associated with higher risks of mechanical
      complications.

PMID- 22419293
TI  - Single dose oral celecoxib for acute postoperative pain in adults.
AB  - BACKGROUND: This is an update of a review published in The Cochrane Library 2008,
      Issue 4. Celecoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor usually
      prescribed for the relief of chronic pain in osteoarthritis and rheumatoid
      arthritis. Celecoxib is believed to be associated with fewer upper
      gastrointestinal adverse effects than conventional non-steroidal anti
      inflammatory drugs (NSAIDs). Its effectiveness in acute pain was demonstrated in
      the earlier reviews. OBJECTIVES: To assess analgesic efficacy and adverse effects
      of a single oral dose of celecoxib for moderate to severe postoperative pain.
      SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Database, and ClinicalTrials.gov. The
      most recent search was to 3 January 2012. SELECTION CRITERIA: We included
      randomised, double-blind, placebo-controlled trials (RCTs) of adults prescribed
      any dose of oral celecoxib or placebo for acute postoperative pain. DATA
      COLLECTION AND ANALYSIS: Two review authors assessed studies for quality and
      extracted data. We converted summed pain relief (TOTPAR) or pain intensity
      difference (SPID) into dichotomous information, yielding the number of
      participants with at least 50% pain relief over four to six hours, and used this
      to calculate the relative benefit (RB) and number needed to treat to benefit
      (NNT) for one patient to achieve at least 50% of maximum pain relief with
      celecoxib who would not have done so with placebo. We used information on use of
      rescue medication to calculate the proportion of participants requiring rescue
      medication and the weighted mean of the median time to use. MAIN RESULTS: Eight
      studies (1380 participants) met the inclusion criteria. We identified five
      potentially relevant unpublished studies in the most recent searches, but data
      were not available at this time. The number of included studies therefore remains
      unchanged.The NNT for celecoxib 200 mg and 400 mg compared with placebo for at
      least 50% of maximum pain relief over four to six hours was 4.2 (95% confidence
      interval (CI) 3.4 to 5.6) and 2.5 (2.2 to 2.9) respectively. The median time to
      use of rescue medication was 6.6 hours with celecoxib 200 mg, 8.4 with celecoxib
      400 mg, and 2.3 hours with placebo. The proportion of participants requiring
      rescue medication over 24 hours was 74% with celecoxib 200 mg, 63% for celecoxib
      400 mg, and 91% for placebo. The NNT to prevent one patient using rescue
      medication was 4.8 (3.5 to 7.7) and 3.5 (2.9 to 4.6) for celecoxib 200 mg and 400
      mg respectively. Adverse events were generally mild to moderate in severity, and
      were experienced by a similar proportion of participants in celecoxib and placebo
      groups. One serious adverse event probably related to celecoxib was reported.
      AUTHORS' CONCLUSIONS: Single-dose oral celecoxib is an effective analgesic for
      postoperative pain relief. Indirect comparison suggests that the 400 mg dose has
      similar efficacy to ibuprofen 400 mg.

PMID- 22419294
TI  - Steroid hormones for contraception in men.
AB  - BACKGROUND: Male hormonal contraception has been an elusive goal. Administration
      of sex steroids to men can shut off sperm production through effects on the
      pituitary and hypothalamus. However, this approach also decreases production of
      testosterone, so 'add-back' therapy is needed. OBJECTIVES: To summarize all
      randomized controlled trials (RCTs) of male hormonal contraception. SEARCH
      METHODS: In January and February 2012, we searched the computerized databases
      CENTRAL, MEDLINE, POPLINE, and LILACS. We also searched for recent trials in
      ClinicalTrials.gov and ICTRP. Previous searches included EMBASE. We wrote to
      authors of identified trials to seek additional unpublished or published trials.
      SELECTION CRITERIA: We included all RCTs that compared a steroid hormone with
      another contraceptive. We excluded non-steroidal male contraceptives, such as
      gossypol. We included both placebo and active-regimen control groups. DATA
      COLLECTION AND ANALYSIS: The primary outcome measure was the absence of
      spermatozoa on semen examination, often called azoospermia. Data were
      insufficient to examine pregnancy rates and side effects. MAIN RESULTS: We found
      33 trials that met our inclusion criteria. The proportion of men who reportedly
      achieved azoospermia or had no detectable sperm varied widely. A few important
      differences emerged. 1) Levonorgestrel implants (160 MUg daily) combined with
      injectable testosterone enanthate (TE) were more effective than levonorgestrel
      125 ug daily combined with testosterone patches. 2) Levonorgestrel 500 MUg daily
      improved the effectiveness of TE 100 mg injected weekly. 3) Levonorgestrel 250
      MUg daily improved the effectiveness of testosterone undecanoate (TU) 1000 mg
      injection plus TU 500 mg injected at 6 and 12 weeks. 4) Desogestrel 150 MUg was
      less effective than desogestrel 300 MUg (with testosterone pellets). 5) TU 500 mg
      was less likely to produce azoospermia than TU 1000 mg (with levonorgestrel
      implants). 6) Norethisterone enanthate 200 mg with TU 1000 mg led to more
      azoospermia when given every 8 weeks versus 12 weeks. 7) Four implants of 7-alpha
      methyl-19-nortestosterone (MENT) were more effective than two MENT implants. We
      did not conduct any meta-analysis due to intervention differences.Several trials
      showed promising efficacy in percentages with azoospermia. Three examined
      desogestrel and testosterone preparations or etonogestrel and testosterone, and
      two examined levonorgestrel and testosterone. AUTHORS' CONCLUSIONS: No male
      hormonal contraceptive is ready for clinical use. Most trials were small
      exploratory studies. Their power to detect important differences was limited and
      their results imprecise. In addition, assessment of azoospermia can vary by
      sensitivity of the method used. Future trials need more attention to the
      methodological requirements for RCTs. More trials with adequate power would also
      be helpful.

PMID- 22419295
TI  - Human recombinant activated protein C for severe sepsis.
AB  - BACKGROUND: Sepsis is a common and frequently fatal condition. Human recombinant
      activated protein C (APC) has been used to reduce the high rate of death by
      severe sepsis or septic shock. This is an update of a Cochrane review (originally
      published in 2007 and updated in 2008). OBJECTIVES: We assessed the clinical
      effectiveness and safety of APC for the treatment of patients with severe sepsis
      or septic shock. SEARCH METHODS: For this updated review we searched CENTRAL (The
      Cochrane Library 2010, Issue 6); MEDLINE (1966 to June 2010); EMBASE (1980 to
      July 1, 2010); BIOSIS (1965 to July 1, 2010); CINAHL (1982 to 16 June 2010) and
      LILACS (1982 to 16 June 2010). There was no language restriction. SELECTION
      CRITERIA: We included randomized controlled trials (RCTs) assessing the effects
      of APC for severe sepsis in adults and children. We excluded studies on neonates.
      We considered all-cause mortality at day 28, at the end of study follow up, and
      hospital mortality as the primary outcomes. DATA COLLECTION AND ANALYSIS: We
      independently performed study selection, risk of bias assessment and data
      extraction. We estimated relative risks (RR) for dichotomous outcomes. We
      measured statistical heterogeneity using the I(2) statistic. We used a random
      effects model. MAIN RESULTS: We identified one new RCT in this update. We
      included a total of five RCTs involving 5101 participants. For 28-day mortality,
      APC did not reduce the risk of death in adult participants with severe sepsis
      (pooled RR 0.97, 95% confidence interval (CI) 0.78 to 1.22; P = 0.82, I(2) =
      68%). APC use was associated with an increased risk of bleeding (RR 1.47, 95% CI
      1.09 to 2.00; P = 0.01, I(2) = 0%). In paediatric patients, APC did not reduce
      the risk of death (RR 0.98, 95% CI 0.66 to 1.46; P = 0.93). Although the included
      trials had no major limitations most of them modified their original completion
      or recruitment protocols. AUTHORS' CONCLUSIONS: This updated review found no
      evidence suggesting that APC should be used for treating patients with severe
      sepsis or septic shock. Additionally, APC is associated with a higher risk of
      bleeding. Unless additional RCTs provide evidence of a treatment effect, policy
      makers, clinicians and academics should not promote the use of APC.Warning: On
      October 25th 2011, the European Medicines Agency issued a press release on the
      worldwide withdrawal of Xigris (activated protein C / drotrecogin alfa) from the
      market by Eli Lilly due to lack of beneficial effect on 28-day mortality in the
      PROWESS-SHOCK study. Furthermore, Eli Lily has announced the discontinuation of
      all other ongoing clinical trials. The final results of the PROWESS-SHOCK study
      are expected to be published in 2012. This systematic review will be updated when
      results of the PROWESS-SHOCK or other trials are published.

PMID- 22419296
TI  - Caesarean section for non-medical reasons at term.
AB  - BACKGROUND: Caesarean section rates are progressively rising in many parts of the
      world. One suggested reason is increasing requests by women for caesarean section
      in the absence of clear medical indications, such as placenta praevia, HIV
      infection, contracted pelvis and, arguably, breech presentation or previous
      caesarean section. The reported benefits of planned caesarean section include
      greater safety for the baby, less pelvic floor trauma for the mother, avoidance
      of labour pain and convenience. The potential disadvantages, from observational
      studies, include increased risk of major morbidity or mortality for the mother,
      adverse psychological sequelae, and problems in subsequent pregnancies, including
      uterine scar rupture and a greater risk of stillbirth and neonatal morbidity. The
      differences in neonatal physiology following vaginal and caesarean births are
      thought to have implications for the infant, with caesarean section potentially
      increasing the risk of compromised health in both the short and the long term. An
      unbiased assessment of advantages and disadvantages would assist discussion of
      what has become a contentious issue in modern obstetrics. OBJECTIVES: To assess,
      from randomised trials, the effects on perinatal and maternal morbidity and
      mortality, and on maternal psychological morbidity, of planned caesarean delivery
      versus planned vaginal birth in women with no clear clinical indication for
      caesarean section. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (31 January 2012) and reference lists of
      relevant studies. SELECTION CRITERIA: All comparisons of intention to perform
      caesarean section and intention for women to give birth vaginally; random
      allocation to treatment and control groups; adequate allocation concealment;
      women at term with single fetuses with cephalic presentations and no clear
      medical indication for caesarean section. DATA COLLECTION AND ANALYSIS: We
      identified no studies that met the inclusion criteria. MAIN RESULTS: There were
      no included trials. AUTHORS' CONCLUSIONS: There is no evidence from randomised
      controlled trials, upon which to base any practice recommendations regarding
      planned caesarean section for non-medical reasons at term. In the absence of
      trial data, there is an urgent need for a systematic review of observational
      studies and a synthesis of qualitative data to better assess the short- and long
      term effects of caesarean section and vaginal birth.

PMID- 22419297
TI  - Nutrient-enriched formula versus standard term formula for preterm infants
      following hospital discharge.
AB  - BACKGROUND: Preterm infants are often growth-restricted at hospital discharge.
      Feeding infants after hospital discharge with nutrient-enriched formula rather
      than standard term formula might facilitate "catch-up" growth and improve
      development. OBJECTIVES: To determine the effect of feeding nutrient-enriched
      formula compared with standard term formula on growth and development for preterm
      infants following hospital discharge. SEARCH METHODS: We used the standard search
      strategy of the Cochrane Neonatal Review Group. This included searches of the
      Cochrane Central Register of Controlled Trials (The Cochrane Library, 2011, Issue
      4), MEDLINE, EMBASE, and CINAHL (to September 2011), conference proceedings and
      previous reviews. SELECTION CRITERIA: Randomised or quasi-randomised controlled
      trials that compared the effect of feeding preterm infants following hospital
      discharge with nutrient-enriched formula (post-discharge formula or preterm
      formula) compared with standard term formula. DATA COLLECTION AND ANALYSIS: We
      extracted data using the standard methods of the Cochrane Neonatal Review Group,
      with separate evaluation of trial quality and data extraction by two review
      authors. MAIN RESULTS: We found 15 eligible trials in which a total of 1128
      preterm infants participated. The trials were of variable methodological quality
      with lack of allocation concealment and incomplete follow-up in some trials being
      the major potential sources of bias. The trials (N = 10) that compared feeding
      infants with "post-discharge formula" (energy density about 74 kcal/100 ml)
      versus standard term formula (about 67 kcal/100 ml) did not find consistent
      evidence of effects on growth parameters up to 12 to 18 months corrected age. The
      trials (N = 5) that compared feeding with "preterm formula" (about 80 kcal/100
      ml) versus term formula found some evidence of higher rates of growth through
      infancy: weighted mean differences at 12 to 18 months corrected age about 500 g
      in weight, 5 to10 mm in length, and 5 mm in head circumference. Few trials
      assessed neurodevelopmental outcomes and these did not detect any statistically
      significant differences in developmental indices at 18 months corrected age.
      There are not yet any data on growth or development through later childhood.
      AUTHORS' CONCLUSIONS: Current recommendations to prescribe "post-discharge
      formula" for preterm infants following hospital discharge are not supported by
      the available evidence. Some limited evidence exists that feeding preterm infants
      following hospital discharge with "preterm formula" (which is generally only
      available for in-hospital use) may increase growth rates up to 18 months
      corrected age.

PMID- 22419299
TI  - WITHDRAWN: Hyperbaric oxygen therapy for promoting fracture healing and treating
      fracture non-union.
AB  - BACKGROUND: Hyperbaric oxygen therapy (HBOT) consists of intermittently
      administering 100% oxygen at pressures greater than one atmosphere absolute (ATA)
      in a pressure vessel. This technology has been used to treat a variety of
      diseases and has been described as helping patients who have delayed healing or
      established non-union of bony fractures. OBJECTIVES: The aim of this review was
      to assess the evidence for the benefit of hyperbaric oxygen treatment (HBOT) for
      the treatment of delayed bony healing and established non-union of bony
      fractures. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma
      Group Specialised Register (April 2008), the Cochrane Register of Controlled
      Trials (CENTRAL) (The Cochrane Library Issue 2, 2008), MEDLINE (OVID 1966 to
      April week 3, 2008), CINAHL (OVID 1982 to April week 3, 2008), EMBASE (OVID 1980
      to week 17 2008), the locally developed Database of Randomised Controlled Trials
      in Hyperbaric Medicine (available at www.hboevidence.com) from inception to May
      2008, and reference lists of articles. SELECTION CRITERIA: We aimed to include
      all randomised controlled trials that compared the effect of HBOT with no HBOT
      (no treatment or sham). DATA COLLECTION AND ANALYSIS: We planned independent data
      collection by two authors using standardised forms. MAIN RESULTS: No trials met
      the inclusion criteria. We excluded one trial that compared HBOT with no
      treatment because no clinical outcomes were reported. AUTHORS' CONCLUSIONS: This
      systematic review failed to locate any relevant clinical evidence to support or
      refute the effectiveness of HBOT for the management of delayed union or
      established non-union of bony fractures. Good quality clinical trials are needed
      to define the role, if any, of HBOT in the treatment of these injuries.

PMID- 22419298
TI  - Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer.
AB  - BACKGROUND: Epithelial ovarian cancer is diagnosed in 4500 women in the UK each
      year of whom 1700 will ultimately die of their disease.Of all cases 10% to 15%
      are diagnosed early when there is still a good possibility of cure. The treatment
      of early stage disease involves surgery to remove disease often followed by
      chemotherapy. The largest clinical trials of this adjuvant therapy show an
      overall survival (OS) advantage with adjuvant platinum-based chemotherapy but the
      precise role of this treatment in subgroups of women with differing prognoses
      needs to be defined. OBJECTIVES: To systematically review the evidence for
      adjuvant chemotherapy in early stage epithelial ovarian cancer to determine
      firstly whether there is a survival advantage of this treatment over the policy
      of observation following surgery with chemotherapy reserved for treatment of
      disease recurrence, and secondly to determine if clinical subgroups of differing
      prognosis based on histological sub-type, or completeness of surgical staging,
      have more or less to gain from chemotherapy following initial surgery. SEARCH
      METHODS: We performed an electronic search using the Cochrane Gynaecological
      Cancer Specialised Register, Cochrane Central Register of Controlled Trials
      (CENTRAL 2011, Issue 3), MEDLINE (1948 to Aug week 5, 2011) and EMBASE (1980 to
      week 36, 2011). We developed the search strategy using free-text and medical
      subject headings (MESH). SELECTION CRITERIA: We selected randomised clinical
      trials that met the inclusion criteria set out based on the populations,
      interventions, comparisons and outcome measures. DATA COLLECTION AND ANALYSIS:
      Two review authors independently extracted data and assessed trial quality.
      Disagreements were resolved by discussion with a third review author. We
      performed random-effects meta-analyses and subgroup analyses. MAIN RESULTS: Five
      randomised controlled trials (RCTs), enrolling 1277 women, with a median follow
      up of 46 to 121 months, met the inclusion criteria. Four trials were included in
      the meta-analyses and we considered them to be at a low risk of bias. Meta
      analysis of five-year data from three trials indicated that women who received
      adjuvant platinum-based chemotherapy had better overall survival (OS) than those
      who did not (1008 women; hazard ratio (HR) 0.71; 95% confidence interval (CI)
      0.53 to 0.93). Likewise, meta-analysis of five-year data from four trials
      indicated that women who received adjuvant chemotherapy had better progression
      free survival (PFS) than those who did not (1170 women; HR 0.67; 95% CI 0.53 to
      0.84). The trials included in these meta-analyses gave consistent estimates of
      the effects of chemotherapy. In addition, these findings were robust over time
      (10-year PFS: two trials, 925 women; HR 0.67; 95% CI 0.54 to 0.84).Subgroup
      analysis suggested that women who had optimal surgical staging of their disease
      were unlikely to benefit from adjuvant chemotherapy (HR for OS 1.22; 95% CI 0.63
      to 2.37; two trials, 234 women) whereas those who had sub-optimal staging did (HR
      for OS 0.63; 95% CI 0.46 to 0.85; two trials, 772 women). One trial showed a
      benefit from adjuvant chemotherapy among women at high risk (HR for OS 0.48; 95%
      CI 0.32 to 0.72) but not among those at low/medium risk (HR for OS 0.95; 95% CI
      0.54 to 1.66). However, these subgroup findings could be due to chance and should
      be interpreted with caution. AUTHORS' CONCLUSIONS: Adjuvant platinum-based
      chemotherapy is effective in prolonging the survival of the majority of patients
      who are assessed as having early (FIGO stage I/IIa) epithelial ovarian cancer.
      However, it may be withheld from women in whom there is well-differentiated
      encapsulated unilateral disease (stage 1a grade 1) or those with comprehensively
      staged Ib, well or moderately differentiated (grade 1/2) disease. Others with
      unstaged early disease or those with poorly differentiated tumours should be
      offered chemotherapy. A pragmatic approach may be necessary in clinical settings
      where optimal staging is not normally performed/achieved. In such settings,
      adjuvant chemotherapy may be withheld from those with encapsulated stage Ia grade
      1 serous and endometrioid carcinoma and offered to all others with early stage
      disease.

PMID- 22419300
TI  - Chinese medicinal herbs for sore throat.
AB  - BACKGROUND: Chinese herbal medicines are commonly used to treat sore throat in
      China and are used worldwide by practitioners of traditional Chinese medicine
      (TCM). Their efficacy in treating sore throat has not previously been
      systematically reviewed. OBJECTIVES: To assess the efficacy and safety of Chinese
      herbal medicines for patients with sore throat. SEARCH METHODS: We searched
      CENTRAL (The Cochrane Library Issue 4, 2011) which contains the Cochrane Acute
      Respiratory Infections Group's Specialised Register; MEDLINE (1966 to week 3,
      November 2011); EMBASE (1980 to December 2011); AMED (1985 to December 2011); the
      Chinese Biomedical Database (CBM) (1975 to December 2011); and China National
      Knowledge Infrastructure (CNKI) (1994 to December 2011). SELECTION CRITERIA: We
      included randomised controlled trial (RCTs) assessing Chinese herbal medicines
      for the treatment of sore throat, with the outcomes of recovery, inefficacy, and
      adverse events. DATA COLLECTION AND ANALYSIS: The three review authors extracted
      and analysed the data. One review author contacted the study authors of potential
      RCTs. MAIN RESULTS: We included 12 studies involving 1954 participants. We
      identified ten studies as being of methodologically poor quality and two studies
      as being of medium quality. We did not perform a meta-analysis but reported the
      results separately. Six formulations were shown to be superior to the control in
      improving recovery: Ertong Qingyan Jiere Koufuye was more effective than Fufang
      Shuanghua Koufuye for acute pharyngitis (odds ratio (OR) 2.52; 95% confidence
      interval (Cl) 1.11 to 5.74); Yanhouling mixture was more effective than
      gentamicin atomised inhalation for acute pharyngitis (OR 5.39; 95% CI 2.69 to
      10.81); Qinganlan Liyan Hanpian was more effective than Fufang Caoshanhu Hanpian
      for acute pharyngitis (OR 2.25; 95% CI 1.08 to 4.67); sore throat capsules were
      more effective than antibiotics (intravenous cefalexin) for acute pharyngitis or
      acute tonsillitis (OR 2.36; 95% CI 1.01 to 5.51); compound dandelion soup was
      more effective than sodium penicillin for acute purulent tonsillitis (OR 5.06;
      95% CI 1.70 to 15.05); and eliminating heat by nourishing yin and relieving sore
      throat methods combined with Dikuiluqan Hanpian was more effective than
      Dikuiluqan Hanpian alone for children with chronic pharyngitis (OR 2.63; 95% CI
      1.02 to 6.79). Another six formulations were shown to be equally efficacious as
      the control. AUTHORS' CONCLUSIONS: Based on the existing evidence in this review,
      some Chinese herbal medicines for treating sore throat appeared efficacious.
      However, due to the lack of high quality clinical trials, the efficacy of Chinese
      herbal medicine for treating sore throat is controversial and questionable.
      Therefore we cannot recommend any kind of Chinese medical herbal formulation as
      an effective remedy for sore throat.

PMID- 22419301
TI  - Human recombinant activated factor VII for upper gastrointestinal bleeding in
      patients with liver diseases.
AB  - BACKGROUND: Mortality from upper gastrointestinal bleeding in patients with liver
      disease is high. Recombinant human activated factor VII (rHuFVIIa) has been
      suggested for patients with liver disease and upper gastrointestinal bleeding.
      OBJECTIVES: To assess the beneficial and harmful effects of rHuFVIIa in patients
      with liver disease and upper gastrointestinal bleeding. SEARCH METHODS: We
      searched the Cochrane Hepato-Biliary Group Controlled Trials Register (December
      2011), the Cochrane Central Register of Controlled Trials (CENTRAL) in The
      Cochrane Library (Issue 4, 2011), MEDLINE (1948 to December 2011), EMBASE (1980
      to December 2011), Science Citation Index Expanded (1900 to December 2011), and
      LILACS (December 2011). We sought additional randomised trials from the reference
      lists of the trials and reviews identified through the electronic searches.
      SELECTION CRITERIA: Randomised clinical trials. DATA COLLECTION AND ANALYSIS:
      Outcome data from randomised clinical trials were extracted and were presented
      using random-effects model meta-analyses. Data on the risk of bias in the
      included trials were also extracted. MAIN RESULTS: We included two trials with
      493 randomised participants with various Child-Pugh scores. The trials had a low
      risk of bias. The rHuFVIIa administration did not reduce the risk of mortality
      within five days (21/288 (7.3%) versus 15/205 (7.3%); risk ratio (RR) 0.88, 95%
      confidence interval (CI) 0.48 to 1.64, I(2) = 49%) and within 42 days (5/286
      (1.7%) versus 36/205 (17.6%); RR 1.01, 95% CI 0.55 to 1.87, I(2) = 55%) when
      compared with placebo. Trial sequential analysis demonstrated that there is
      sufficient evidence to exclude that rHuFVIIa decreases mortality by 80%, but
      there is insufficient evidence to exclude smaller effects. The rHuFVIIa did not
      increase the risk of adverse events by number of patients (218/297 (74%) and
      164/210 (78%); RR 0.94, 95% CI 0.84 to 1.04, I(2) = 1%), serious adverse events
      by adverse events reported (164/590 (28%) versus 123/443 (28%); RR 0.91, 95% CI
      0.75 to 1.11, I(2) = 0%), and thromboembolic adverse events (16/297 (5.4%) versus
      14/210 (6.7%); RR 0.80, 95% CI 0.40 to 1.60, I(2) = 0%) when compared with
      placebo. AUTHORS' CONCLUSIONS: We found no evidence to support or reject the
      administration of rHuFVIIa for patients with liver disease and upper
      gastrointestinal bleeding. Further adequately powered randomised clinical trials
      are needed in order to evaluate the proper role of rHuFVIIa for treating upper
      gastrointestinal bleeding in patients with liver disease. Although the results
      are based on trials with low risk of bias, the heterogeneity and the small sample
      size result in rather large confidence intervals that cannot exclude the
      possibility that the intervention has some beneficial or harmful effect. Further
      trials with alow risk of bias are required to make more confident conclusions
      about the effects of the intervention.

PMID- 22419302
TI  - Treatment for superficial thrombophlebitis of the leg.
AB  - BACKGROUND: The optimal treatment of superficial thrombophlebitis (ST) of the
      legs remains poorly defined. While improving or relieving the local painful
      symptoms, treatment should aim at preventing venous thromboembolism (VTE), which
      might complicate the natural history of ST. This is an update of a review first
      published in 2007. OBJECTIVES: To assess the efficacy and safety of topical,
      medical, and surgical treatments in patients presenting with ST of the legs.
      SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group
      searched their Specialised Register (last searched 29 November 2011) and CENTRAL
      (2011, Issue 4). We handsearched reference lists of relevant papers and
      conference proceedings. SELECTION CRITERIA: Randomised controlled trials (RCTs)
      evaluating topical, medical, and surgical treatments for ST of the leg that
      included participants with a clinical diagnosis of ST of the legs or objective
      diagnosis of a thrombus in the superficial vein. DATA COLLECTION AND ANALYSIS:
      Two authors assessed the trials for inclusion in the review, extracted the data,
      and assessed the quality of the studies. Data were independently extracted from
      the included studies and any disagreements resolved by consensus. MAIN RESULTS:
      Twenty-six studies involving 5521 participants with ST of the legs were included
      in this review. The methodological quality of most of the trials was poor.
      Treatment ranged from fondaparinux, low molecular weight heparin (LMWH),
      unfractionated heparin (UFH), non-steroidal anti-inflammatory agents (NSAIDs),
      topical treatment, oral treatment, intramuscular treatment, and intravenous
      treatment to surgery. In a placebo-controlled RCT of about 3000 patients,
      fondaparinux was associated with a significant reduction in symptomatic VTE (RR
      0.15; 95% CI 0.04 to 0.50), extension (RR 0.08; 95% CI 0.03 to 0.22), and
      recurrence of ST (RR 0.21; 95% CI 0.08 to 0.54) with comparable rates of major
      bleeding (RR 0.99; 95% CI 0.06 to 15.86) relative to placebo. Both prophylactic
      and therapeutic doses of LMWH (RR 0.40; 95% CI 0.22 to 0.72 and RR 0.42; 95% CI
      0.23 to 0.75, respectively) and NSAIDs (RR 0.41; 95% CI 0.23 to 0.75) reduced the
      extension and recurrence of ST in comparison to placebo, with no significant
      effects on symptomatic VTE nor major bleeding. Overall, topical treatments
      improved local symptoms. However, no data were provided on the effects of these
      treatments on VTE and ST extension. Surgical treatment combined with elastic
      stockings in ST was associated with a lower VTE rate and ST progression compared
      with elastic stockings alone. AUTHORS' CONCLUSIONS: Prophylactic dose
      fondaparinux given for six weeks appears to be a valid therapeutic option for ST
      of the legs. Further research is needed to assess the role of new oral direct
      thrombin and activated factor-X inhibitors, LMWH, NSAIDs; the optimal doses and
      duration of treatment; and whether a combination therapy may be more effective
      than single treatment. Adequately designed and conducted studies are required to
      clarify the role of topical and surgical treatments.

PMID- 22419303
TI  - Recombinant factor VIIa for the prevention and treatment of bleeding in patients
      without haemophilia.
AB  - BACKGROUND: Recombinant factor VIIa (rFVIIa) is licensed for use in patients with
      haemophilia and inhibitory allo-antibodies and for prophylaxis and treatment of
      patients with congenital factor VII deficiency. It is also used for off-license
      indications to prevent bleeding in operations where blood loss is likely to be
      high, and/or to stop bleeding that is proving difficult to control by other
      means. This is the third version of the 2007 Cochrane review on the use of
      recombinant factor VIIa for the prevention and treatment of bleeding in patients
      without haemophilia, and has been updated to incorporate recent trial data.
      OBJECTIVES: To assess the effectiveness of rFVIIa when used therapeutically to
      control active bleeding or prophylactically to prevent (excessive) bleeding in
      patients without haemophilia. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other medical
      databases up to 23 March 2011. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) comparing rFVIIa with placebo, or one dose of rFVIIa with another, in any
      patient population (except haemophilia). Outcomes were mortality, blood loss or
      control of bleeding, red cell transfusion requirements, number of patients
      transfused and thromboembolic adverse events. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed potentially relevant studies for inclusion,
      extracted data and examined risk of bias. We considered prophylactic and
      therapeutic rFVIIa studies separately. MAIN RESULTS: Twenty-nine RCTs were
      included: 28 were placebo-controlled, double-blind RCTs and one compared
      different doses of rFVIIa. In the 'Risk of bias' assessment, most studies were
      found to have some threats to validity although therapeutic RCTs were found to be
      less prone to bias than prophylactic RCTs.Sixteen trials involving 1361
      participants examined the prophylactic use of rFVIIa; 729 received rFVIIa. There
      was no evidence of mortality benefit (risk ratio (RR) 1.04; 95% confidence
      interval (CI) 0.55 to 1.97). There was decreased blood loss (mean difference (MD)
      -297 mL; 95% CI -416 to -178) and decreased red cell transfusion requirements (MD
      -261 mL; 95% CI -367 to -154) with rFVIIa treatment; however, these values were
      likely overestimated due to the inability to incorporate data from trials (four
      RCTs in the outcome of blood loss and three RCTs in the outcome of transfusion
      requirements) showing no difference of rFVIIa treatment compared to placebo.
      There was a trend in favour of rFVIIa in the number of participants transfused
      (RR 0.85; 95% CI 0.72 to 1.01). However, there was a trend against rFVIIa with
      respect to thromboembolic adverse events (RR 1.35; 95% CI 0.82 to 2.25).Thirteen
      trials involving 2929 participants examined the therapeutic use of rFVIIa; 1878
      received rFVIIa. There were no outcomes where any observed advantage or
      disadvantage of rFVIIa over placebo could not have been observed by chance alone.
      There was a trend in favour of rFVIIa for reducing mortality (RR 0.91; 95% CI
      0.78 to 1.06). However, there was a trend against rFVIIa for increased
      thromboembolic adverse events (RR 1.14; 95% CI 0.89 to 1.47).When all trials were
      pooled together to examine the risk of thromboembolic events, a significant
      increase in total arterial events was observed (RR 1.45; 95% CI 1.02 to 2.05).
      AUTHORS' CONCLUSIONS: The effectiveness of rFVIIa as a more general haemostatic
      drug, either prophylactically or therapeutically, remains unproven. The results
      indicate increased risk of arterial events in patients receiving rFVIIa. The use
      of rFVIIa outside its current licensed indications should be restricted to
      clinical trials.

PMID- 22419304
TI  - Sodium channel blockers for cystic fibrosis.
AB  - BACKGROUND: People with cystic fibrosis (CF) have increased transport of the
      salt, sodium across their airway lining. Over-absorption of sodium results in the
      dehydration of the liquid that lines the airway surface and is a primary defect
      in people with CF. OBJECTIVES: To determine whether the topical administration of
      drugs that block sodium transport improves the respiratory condition of people
      with CF. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic
      Disorders Group Trials Register comprising references identified from
      comprehensive electronic database searches, handsearching relevant journals and
      abstract books of conference proceedings. We contacted principal investigators
      known to work in the field, previous authors and pharmaceutical companies who
      manufacture ion transport agents for unpublished or follow-up data.Most recent
      search of the Group's register: 22nd August 2011. SELECTION CRITERIA: Published
      or unpublished randomised controlled trials (RCTs) or quasi-randomised controlled
      trials of sodium channel blockers compared to placebo or another sodium channel
      blocker or the same sodium channel blocker at a different dosing regimen. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted data. Meta-analysis
      was limited due to differing study designs. MAIN RESULTS: Five RCTs, with a total
      of 226 participants, examining the topical administration of the short-acting
      sodium channel blocker, amiloride, compared to placebo were identified as
      eligible for inclusion in the review. In three studies over six months, there was
      a significant difference found in the difference in relative change in FVC in
      favour of placebo (weighted mean difference 1.51% (95% confidence interval -2.77
      to -0.25), although heterogeneity was evident. A two-week study demonstrated that
      hypertonic saline with amiloride pre-treatment did not result in a significant
      improvement in respiratory function or mucus clearance, in contrast to pre
      treatment with placebo. There were no significant differences identified in other
      clinically relevant outcomes. AUTHORS' CONCLUSIONS: We found no evidence that the
      topical administration of a short-acting sodium channel blocker improves
      respiratory condition in people with cystic fibrosis and some limited evidence of
      deterioration in lung function.

PMID- 22419305
TI  - Enteral iron supplementation in preterm and low birth weight infants.
AB  - BACKGROUND: Preterm infants are at risk of exhausting their body iron stores much
      earlier than healthy term newborns. It is widespread practice to give enteral
      iron supplementation to preterm and low birth weight infants to prevent iron
      deficiency anaemia. However, it is unclear whether supplementing preterm and low
      birth weight infants with iron improves growth and neurodevelopment. It is
      suspected that excess exogenous iron can contribute to oxidative injury in
      preterm babies, causing or exacerbating conditions such as necrotising
      enterocolitis and retinopathy of prematurity. Additionally, the optimal dose and
      timing of commencement and cessation of iron supplementation are uncertain.
      OBJECTIVES: To evaluate the effect of prophylactic enteral iron supplementation
      on growth and neurodevelopmental outcomes in preterm and low birth weight
      infants. The secondary objectives were to determine whether iron supplementation
      results in improved haematological parameters and prevents other causes of
      morbidity and mortality. SEARCH METHODS: We used the standard search strategy of
      the Cochrane Neonatal Review Group. We searched Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 8), MEDLINE (1951
      to August 2011), CINAHL (1982 to August 2011) and conference proceedings and
      previous reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs) and
      quasi-randomised trials that compared enteral iron supplementation with no iron
      supplementation, or different regimens of enteral iron supplementation in preterm
      or low birth weight infants or both. DATA COLLECTION AND ANALYSIS: We extracted
      data using the standard methods of the Cochrane Neonatal Review Group. Both
      review authors separately evaluated trial quality and data extraction. We
      synthesised data using risk ratios (RRs), risk differences (RDs) and weighted
      mean differences (WMDs). Where data about the methodology and results or both
      were lacking, we made an attempt to contact the study authors for further
      information. MAIN RESULTS: We included twenty-six studies (2726 infants) in the
      analysis. The heterogeneity of participants, methods and results precluded an
      extensive quantitative synthesis. Of the 21 studies comparing iron
      supplementation with controls, none evaluated neurodevelopmental status as an
      outcome. Of thirteen studies reporting at least one growth parameter as an
      outcome, only one study of poor quality found a significant benefit of iron
      supplementation. Regarding haematological outcomes, no benefit for iron
      supplementation was demonstrated within the first 8.5 weeks of postnatal life (16
      trials), except by two poor quality studies. After this age, most studies
      reported a higher mean haemoglobin in iron-supplemented infants. We were only
      able to include a limited number of studies in a quantitative meta-analysis,
      which suggested the haemoglobin concentration in iron-supplemented infants was
      higher by about 6 g/L at six to nine months. One study comparing high dose and
      low dose iron supplementation monitored neurodevelopmental outcome for one year,
      without finding any significant difference between the groups. One study
      comparing early versus late commencement of iron supplementation found no
      difference in cognitive outcome, but an increased rate of abnormal neurological
      examination in the late iron group at five years of age. The studies comparing
      high and low doses of iron indicated that there was no discernible haematological
      benefit in exceeding 'standard' doses of iron (i.e. 2 mg/kg/day to 3 mg/kg/day).
      AUTHORS' CONCLUSIONS: The available data suggest that infants who receive iron
      supplementation have a slightly higher haemoglobin level, improved iron stores
      and a lower risk of developing iron deficiency anaemia when compared with those
      who are unsupplemented. However, it is unclear whether iron supplementation in
      preterm and low birth weight infants has long term benefits in terms of
      neurodevelopmental outcome and growth. The optimum timing and duration of iron
      supplementation remains unclear.

PMID- 22419306
TI  - Patient education for neck pain.
AB  - BACKGROUND: Neck disorders are common, disabling, and costly. The effectiveness
      of patient education strategies is unclear. OBJECTIVES: To assess the short- to
      long-term effects of therapeutic patient education (TPE) strategies on pain,
      function, disability, quality of life, global perceived effect, patient
      satisfaction, knowledge transfer, or behaviour change in adults with neck pain
      associated with whiplash or non-specific and specific mechanical neck pain with
      or without radiculopathy or cervicogenic headache. SEARCH METHODS: We searched
      computerised bibliographic databases (inception to 11 July 2010). SELECTION
      CRITERIA: Eligible studies were randomised controlled trials (RCT) investigating
      the effectiveness of TPE for acute to chronic neck pain. DATA COLLECTION AND
      ANALYSIS: Paired independent review authors conducted selection, data
      abstraction, and 'Risk of bias' assessment. We calculated risk ratio (RR) and
      standardised mean differences (SMD). Heterogeneity was assessed; no studies were
      pooled. MAIN RESULTS: Of the 15 selected trials, three were rated low risk of
      bias. Three TPE themes emerged.Advice focusing on activation: There is moderate
      quality evidence (one trial, 348 participants) that an educational video of
      advice focusing on activation was more beneficial for acute whiplash-related pain
      when compared with no treatment at intermediate-term [RR 0.79 (95% confidence
      interval (CI) 0.59 to 1.06)] but not long-term follow-up [0.89 (95% CI, 0.65 to
      1.21)]. There is low quality evidence (one trial, 102 participants) that a
      whiplash pamphlet on advice focusing on activation is less beneficial for pain
      reduction, or no different in improving function and global perceived improvement
      from generic information given out in emergency care (control) for acute whiplash
      at short- or intermediate-term follow-up. Low to very low quality evidence (nine
      trials using diverse educational approaches) showed either no evidence of benefit
      or difference for varied outcomes. Advice focusing on pain & stress coping skills
      and workplace ergonomics: Very low quality evidence (three trials, 243
      participants) favoured other treatment or showed no difference spanning numerous
      follow-up periods and disorder subtypes.  Low quality evidence (one trial, 192
      participants) favoured specific exercise training for chronic neck pain at short
      term follow-up.Self-care strategies: Very low quality evidence (one trial, 58
      participants) indicated that self-care strategies did not relieve pain for acute
      to chronic neck pain at short-term follow-up. AUTHORS' CONCLUSIONS: With the
      exception of one trial, this review has not shown effectiveness for educational
      interventions, including advice to activate, advice on stress-coping skills,
      workplace ergonomics and self-care strategies. Future research should be founded
      on sound adult learning theory and learning skill acquisition.

PMID- 22419307
TI  - Perioperative antibiotics to prevent infection after first-trimester abortion.
AB  - BACKGROUND: There are two main strategies for the prevention of post-abortal
      upper genital tract infection: antibiotics given around the time of surgery for
      all women; and 'screen-and-treat', in which all women presenting for abortion are
      screened for genital infections and those with positive results are treated.
      OBJECTIVES: To determine:1. the effectiveness of antibiotic prophylaxis in
      preventing post-abortal upper genital tract infection; 2. the most effective
      antibiotic regimen; 3. the most effective strategy. SEARCH METHODS: We searched
      the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE,
      POPLINE and LILACS. The search was last updated in May 2011. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) in any language including women undergoing
      induced first trimester surgical or medical abortion, comparing: 1) any
      antibiotic regimen to placebo, nothing, or another antibiotic; 2) screen-and
      treat versus antibiotics. The primary outcome was the proportion of women
      diagnosed with post-abortal upper genital tract infection. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently selected references and extracted data. We
      calculated risk ratios (RR) with 95% confidence intervals (CI). We used meta
      analysis where appropriate and examined between trial heterogeneity using the
      I(2) statistic. In the presence of between trial heterogeneity we also estimated
      the 95% prediction interval (PI). MAIN RESULTS: A total of 703 unique items was
      identified. We included 19 RCTs. There was evidence of small study biases (Egger
      test, P = 0.002). In 15 placebo-controlled RCTs there was an effect of antibiotic
      prophylaxis (pooled RR 0.59, 95% CI 0.46 to 0.75, 95% PI 0.30 to 1.14, I(2) =
      39%). There were insufficient data (three trials) to determine whether one
      regimen was superior to another. In one trial, the incidence of post-abortal
      upper genital tract infection was higher in women allocated to the screen-and
      treat strategy (RR 1.53, 95% CI 0.99 to 2.36). AUTHORS' CONCLUSIONS: Antibiotic
      prophylaxis at the time of first trimester surgical abortion is effective in
      preventing post-abortal upper genital tract infection. Evidence of between trial
      heterogeneity suggests that the effect might not apply to all settings,
      population groups or interventions.This review did not determine the most
      effective antibiotic prophylaxis regimen. Antibiotic choice should take into
      account the local epidemiology of genital tract infections, including sexually
      transmitted infections.Further RCTs comparing different antibiotics or
      combinations of antibiotics with each other would be useful. Such trials could be
      done in low and middle income countries and where the prevalence of genital tract
      infections in women presenting for abortion is high.

PMID- 22419308
TI  - Sensory environment on health-related outcomes of hospital patients.
AB  - BACKGROUND: Hospital environments have recently received renewed interest, with
      considerable investments into building and renovating healthcare estates.
      Understanding the effectiveness of environmental interventions is important for
      resource utilisation and providing quality care. OBJECTIVES: To assess the effect
      of hospital environments on adult patient health-related outcomes. SEARCH
      METHODS: We searched: the Cochrane Central Register of Controlled Trials (last
      searched January 2006); MEDLINE (1902 to December 2006); EMBASE (January 1980 to
      February 2006); 14 other databases covering health, psychology, and the built
      environment; reference lists; and organisation websites. This review is currently
      being updated (MEDLINE last search October 2010), see Studies awaiting
      classification. SELECTION CRITERIA: Randomised and non-randomised controlled
      trials, controlled before-and-after studies, and interrupted times series of
      environmental interventions in adult hospital patients reporting health-related
      outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently
      undertook data extraction and 'Risk of bias' assessment. We contacted authors to
      obtain missing information. For continuous variables, we calculated a mean
      difference (MD) or standardized mean difference (SMD), and 95% confidence
      intervals (CI) for each study. For dichotomous variables, we calculated a risk
      ratio (RR) with 95% confidence intervals (95% CI). When appropriate, we used a
      random-effects model of meta-analysis. Heterogeneity was explored qualitatively
      and quantitatively based on risk of bias, case mix, hospital visit
      characteristics, and country of study. MAIN RESULTS: Overall, 102 studies have
      been included in this review. Interventions explored were: 'positive
      distracters', to include aromas (two studies), audiovisual distractions (five
      studies), decoration (one study), and music (85 studies); interventions to reduce
      environmental stressors through physical changes, to include air quality (three
      studies), bedroom type (one study), flooring (two studies), furniture and
      furnishings (one study), lighting (one study), and temperature (one study); and
      multifaceted interventions (two studies). We did not find any studies meeting the
      inclusion criteria to evaluate: art, access to nature for example, through
      hospital gardens, atriums, flowers, and plants, ceilings, interventions to reduce
      hospital noise, patient controls, technologies, way-finding aids, or the
      provision of windows. Overall, it appears that music may improve patient-reported
      outcomes such as anxiety; however, the benefit for physiological outcomes, and
      medication consumption has less support. There are few studies to support or
      refute the implementation of physical changes, and except for air quality, the
      included studies demonstrated that physical changes to the hospital environment
      at least did no harm. AUTHORS' CONCLUSIONS: Music may improve patient-reported
      outcomes in certain circumstances, so support for this relatively inexpensive
      intervention may be justified. For some environmental interventions, well
      designed research studies have yet to take place.

PMID- 22419309
TI  - Workload and surgeon's specialty for outcome after colorectal cancer surgery.
AB  - BACKGROUND: A large body of research has focused on investigating the effects of
      healthcare provider volume and specialization on patient outcomes including
      outcomes of colorectal cancer surgery. However there is conflicting evidence
      about the role of such healthcare provider characteristics in the management of
      colorectal cancer. OBJECTIVES: To examine the available literature for the
      effects of hospital volume, surgeon caseload and specialization on the outcomes
      of colorectal, colon and rectal cancer surgery. SEARCH METHODS: We searched
      Cochrane Central Register of Controlled Trials (CENTRAL), and LILACS using free
      text search words (as well as MESH-terms). We also searched Medline (January 1990
      September 2011), Embase (January 1990-September 2011) and registers of clinical
      trials, abstracts of scientific meetings, reference lists of included studies and
      contacted experts in the field. SELECTION CRITERIA: Non-randomised and
      observational studies that compared outcomes for colorectal cancer, colon cancer
      and rectal cancer surgery (overall 5-year survival, five year disease specific
      survival, operative mortality, 5-year local recurrence rate, anastomotic leak
      rate, permanent stoma rate and abdominoperineal excision of the rectum rate)
      between high volume/specialist hospitals and surgeons and low volume/specialist
      hospitals and surgeons. DATA COLLECTION AND ANALYSIS: Two review authors
      independently abstracted data and assessed risk of bias in included studies.
      Results were pooled using the random effects model in unadjusted and case-mix
      adjusted meta-analyses. MAIN RESULTS: Overall five year survival was
      significantly improved for patients with colorectal cancer treated in high-volume
      hospitals (HR=0.90, 95% CI 0.85 to 0.96), by high-volume surgeons (HR=0.88, 95%
      CI 0.83 to 0.93) and colorectal specialists (HR=0.81, 95% CI 0.71 to 0.94).
      Operative mortality was significantly better for high-volume surgeons (OR=0.77,
      95% CI 0.66 to 0.91) and specialists (OR=0.74, 95% CI 0.60 to 0.91), but there
      was no significant association with higher hospital caseload (OR=0.93, 95% CI
      0.84 to 1.04) when only case-mix adjusted studies were included. There were
      differences in the effects of caseload depending on the level of case-mix
      adjustment and also whether the studies originated in the US or in other
      countries. For rectal cancer, there was a significant association between high
      volume hospitals and improved 5-year survival (HR=0.85, 95% CI 0.77 to 0.93), but
      not with operative mortality (OR=0.97, 95% CI 0.70 to 1.33); surgeon caseload had
      no significant association with either 5-year survival (HR=0.99, 95% CI 0.86 to
      1.14) or operative mortality (OR=0.86, 95% CI 0.62 to 1.19) when case-mix
      adjusted studies were reviewed. Higher hospital volume was associated with
      significantly lower rates of permanent stomas (OR=0.64, 95% CI 0.45 to 0.90) and
      APER (OR=0.55, 95% CI 0.42 to 0.72). High-volume surgeons and specialists also
      achieved lower rates of permanent stoma formation (0.75, 95% CI 0.64 to 0.88) and
      (0.70, 95% CI 0.53 to 0.94, respectively). AUTHORS' CONCLUSIONS: The results
      confirm clearly the presence of a volume-outcome relationship in colorectal
      cancer surgery, based on hospital and surgeon caseload, and specialisation. The
      volume-outcome relationship appears somewhat stronger for the individual surgeon
      than for the hospital; particularly for overall 5-year survival and operative
      mortality, there were differences between US and non-US data, suggesting provider
      variability at hospital level between different countries, making it imperative
      that every country or healthcare system must establish audit systems to guide
      changes in the service provision based on local data, and facilitate
      centralisation of services as required. Overall quality of the evidence was low
      as all included studies were observational by design. In addition there were
      discrepancies in the definitions of caseload and colorectal specialist. However
      ethical challenges associated with the conception of randomised controlled trials
      addressing the volume outcome relationship makes this the best available
      evidence.

PMID- 22419310
TI  - Medications for increasing milk supply in mothers expressing breastmilk for their
      preterm hospitalised infants.
AB  - BACKGROUND: Breastmilk remains the optimal form of enteral nutrition for term and
      preterm infants until up to six months postnatal age. Mothers of preterm infants
      who have not established suck feeds must express their breastmilk and often have
      difficulty in maintaining sufficient volume for their infants' needs (Donath
      2008). In preterm infants, donor breastmilk reduced the occurrence of necrotising
      enterocolitis, when compared with formula feeds (McGuire 2003). Also, case
      control studies have suggested that breastmilk is associated with an improvement
      in feeding tolerance, a reduction in significant gastrointestinal infective
      events (Beeby 1992) and a reduction in late-onset sepsis (Schanler 1999) when
      compared with formula feeds in preterm hospitalised infants. OBJECTIVES: To
      assess the effect of medication given for at least seven days to mothers of
      preterm infants whose breastmilk is insufficient for their infants' needs on the
      outcomes of expressed milk volume and duration of breastfeeding. SEARCH METHODS:
      We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31
      December 2011). SELECTION CRITERIA: Randomised and quasi-randomised controlled
      trials of breastmilk-augmenting medications (compared with placebo or with other
      augmenting medications) in mothers with preterm hospitalised infants whose
      breastmilk volumes failed to meet their infants' requirements. We did not include
      trials with a cluster-randomised or cross-over design. DATA COLLECTION AND
      ANALYSIS: Both review authors independently assessed studies for inclusion,
      assessed risk of bias, and extracted data. Any differences were resolved by
      consensus. Data were checked for accuracy. MAIN RESULTS: Two trials (involving 59
      mothers) that examined the use of domperidone in a total of 59 mother-infant
      pairs met the inclusion criteria. Meta-analysis of these trials showed a modest
      increase in expressed breastmilk (EBM) of 99.49 mL/day (95% confidence intervals 
      1.94 to 200.92; random-effects, T2 3511.62, I2 63%) in mothers given domperidone.
      Both trials gave the same dose of domperidone (10 mg three times per day) with a
      duration of seven days in the smaller trial and 14 days in the larger.Neither
      trial showed significant improvements in longer-term outcomes of breastfeeding in
      a preterm population and no adverse effects were reported. AUTHORS' CONCLUSIONS:
      Two studies with a total of 59 mothers suggest modest improvements in short-term
      EBM volumes when a medication is used after insufficient EBM occurs in mothers
      following preterm delivery. In both studies, the medication was commenced ?14
      days post delivery and following insufficient EBM supply with other lactation
      supports.Currently, no studies support prophylactic use of a galactagogue
      medication at any gestation. Use of any galactagogue medication has only been
      examined at more than 14 days post delivery and after full lactation support has
      been given. Further trials should examine larger groups of preterm mothers and
      consider breastfeeding outcomes over a longer period.

PMID- 22419311
TI  - Umbilical vein injection for the routine management of third stage of labour.
AB  - BACKGROUND: Postpartum haemorrhage is among the biggest contributor to maternal
      mortality worldwide. Prevention of this condition includes routine use of
      uterotonic in the third stage of labour, which has been recommended throughout
      the world. Use of umbilical route to deliver this uterotonic after delivery of
      the baby has been proposed. Therapeutic use of this has been assessed, although
      routine (prophylactic) use of this has not been evaluated. OBJECTIVES: To
      compare, from the best available evidence, the effects of umbilical vein
      injection of a saline solution alone or with any uterotonic drug versus an
      alternative solution with or without any other uterotonic agent or expectant
      management or any other method for routine management of the third stage of
      labour, on maternal and perinatal outcomes. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2012) and
      reference lists of retrieved studies. SELECTION CRITERIA: We included all
      randomised controlled trials comparing the effects of umbilical vein injection of
      a saline solution alone or with any uterotonic drug versus any other alternative
      methods. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      the eligibility and trial quality. Two review authors extracted data. Data were
      checked for accuracy. MAIN RESULTS: We included nine studies involving 1118
      women.We identified four comparisons. One comparison included six studies (which
      randomised 394 women) comparing umbilical vein injection of normal saline plus
      oxytocin versus that of normal saline, as well as three other comparisons, each
      of which includes one study. Comparing intraumbilical injection of normal saline
      plus oxytocin with intraumbilical injection of saline only, there was no evidence
      of difference in any of the relevant outcomes reported namely the number of women
      who required blood transfusion, the incidence of manual removal of placenta,
      blood loss, and length of the third stage of labour. Subgroup analyses by both
      total amount of solution administered and dose of oxytocin showed no evidence of
      difference. Other comparisons included only one study for each, and there was no
      relevant information available. AUTHORS' CONCLUSIONS: Routine use of oxytocin or
      any other uterotonics with normal saline via umbilical vein injection is not
      recommended until new evidence is available. Further research should be conducted
      to show effectiveness of oxytocin with normal saline via umbilical vein
      injection.

PMID- 22419312
TI  - Garlic for the common cold.
AB  - BACKGROUND: Garlic is alleged to have antimicrobial and antiviral properties that
      relieve the common cold, among other beneficial effects. There is widespread
      usage of garlic supplements. The common cold is associated with significant
      morbidity and economic consequences. On average, children have six to eight colds
      per year and adults have two to four. OBJECTIVES: To determine whether garlic
      (allium sativum) is effective for either the prevention or treatment of the
      common cold, when compared to placebo, no treatment or other treatments. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL)
      (2011, Issue 4), which includes the Cochrane Acute Respiratory Infections Group
      Specialised Register, OLDMEDLINE (1950 to 1965), MEDLINE (January 1966 to
      November week 3, 2011), EMBASE (1974 to December 2011) and AMED (1985 to December
      2011). SELECTION CRITERIA: Randomised controlled trials of common cold prevention
      and treatment comparing garlic with placebo, no treatment or standard treatment.
      DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed and
      selected trials from searches, assessed and rated study quality and extracted
      relevant data. MAIN RESULTS: Of the six trials identified as potentially relevant
      from our searches, only one trial met the inclusion criteria. This trial randomly
      assigned 146 participants to either a garlic supplement (with 180 mg of allicin
      content) or a placebo (once daily) for 12 weeks. The trial reported 24
      occurrences of the common cold in the garlic intervention group compared with 65
      in the placebo group (P < 0.001), resulting in fewer days of illness in the
      garlic group compared with the placebo group (111 versus 366). The number of days
      to recovery from an occurrence of the common cold was similar in both groups
      (4.63 versus 5.63). Only one trial met the inclusion criteria, therefore limited
      conclusions can be drawn. The trial relied on self reported episodes of the
      common cold but was of reasonable quality in terms of randomisation and
      allocation concealment. Adverse effects included rash and odour. AUTHORS'
      CONCLUSIONS: There is insufficient clinical trial evidence regarding the effects
      of garlic in preventing or treating the common cold. A single trial suggested
      that garlic may prevent occurrences of the common cold but more studies are
      needed to validate this finding. Claims of effectiveness appear to rely largely
      on poor-quality evidence.

PMID- 22419313
TI  - Transcutaneous electric nerve stimulation (TENS) for cancer pain in adults.
AB  - BACKGROUND: Cancer-related pain is complex and multi-dimensional but the mainstay
      of cancer pain management has predominantly used a biomedical approach. There is
      a need for non-pharmacological and innovative approaches. Transcutaneous Electric
      Nerve Stimulation (TENS) may have a role in pain management but the effectiveness
      of TENS is currently unknown. This is an update of the original review published
      in Issue 3, 2008. OBJECTIVES: The aim of this systematic review was to determine
      the effectiveness of TENS for cancer-related pain in adults. SEARCH METHODS: The
      initial review searched The Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO,
      AMED and PEDRO databases in April 2008. We performed an updated search of
      CENTRAL, MEDLINE, EMBASE, CINAHL and PEDRO databases in November 2011. SELECTION
      CRITERIA: We included only randomised controlled trials (RCTS) investigating the
      use of TENS for the management of cancer-related pain in adults. DATA COLLECTION
      AND ANALYSIS: The search strategy identified a further two studies for possible
      inclusion. One of the review authors screened each abstract using a study
      eligibility tool. Where eligibility could not be determined, a second author
      assessed the full paper. One author used a standardised data extraction sheet to
      collect information on the studies and independently assess the quality of the
      studies using the validated five-point Oxford Quality Scale. The small sample
      sizes and differences in patient study populations of the three included studies
      (two from the original review and a third included in this update) prevented meta
      analysis. For the original review the search strategy identified 37 possible
      published studies; we divided these between two pairs of review authors who
      decided on study selection; all four review authors discussed and agreed final
      scores. MAIN RESULTS: Only one additional RCT met the eligibility criteria (24
      participants) for this updated review. Although this was a feasibility study, not
      designed to investigate intervention effect, it suggested that TENS may improve
      bone pain on movement in a cancer population. The initial review identified two
      RCTs (64 participants) therefore this review now includes a total of three RCTs
      (88 participants). These studies were heterogenous with respect to study
      population, sample size, study design, methodological quality, mode of TENS,
      treatment duration, method of administration and outcome measures used. In one
      RCT, there were no significant differences between TENS and placebo in women with
      chronic pain secondary to breast cancer treatment. In the other RCT, there were
      no significant differences between acupuncture-type TENS and sham in palliative
      care patients; this study was underpowered. AUTHORS' CONCLUSIONS: Despite the one
      additional RCT, the results of this updated systematic review remain inconclusive
      due to a lack of suitable RCTs. Large multi-centre RCTs are required to assess
      the value of TENS in the management of cancer-related pain in adults.

PMID- 22419314
TI  - Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease
      dementia and cognitive impairment in Parkinson's disease.
AB  - BACKGROUND: Previous Cochrane reviews have considered the use of cholinesterase
      inhibitors in both Parkinson's disease with dementia (PDD) and dementia with Lewy
      bodies (DLB). The clinical features of DLB and PDD have much in common and are
      distinguished primarily on the basis of whether or not parkinsonism precedes
      dementia by more than a year. Patients with both conditions have particularly
      severe deficits in cortical levels of the neurotransmitter acetylcholine.
      Therefore, blocking its breakdown using cholinesterase inhibitors may lead to
      clinical improvement. OBJECTIVES: To assess the efficacy, safety and tolerability
      of cholinesterase inhibitors in dementia with Lewy bodies (DLB), Parkinson's
      disease with dementia (PDD), and cognitive impairment in Parkinson's disease
      falling short of dementia (CIND-PD) (considered as separate phenomena and also
      grouped together as Lewy body disease). SEARCH METHODS: The trials were
      identified from a search of ALOIS, the Specialised Register of the Cochrane
      Dementia and Cognitive Improvement Group (on 30 August 2011) using the search
      terms Lewy, Parkinson, PDD, DLB, LBD. This register consists of records from
      major healthcare databases (MEDLINE, EMBASE, PsycINFO, CINAHL) and many ongoing
      trial databases and is updated regularly.Reference lists of relevant studies were
      searched for additional trials. SELECTION CRITERIA: Randomised, double-blind,
      placebo-controlled trials assessing the efficacy of treatment with cholinesterase
      inhibitors in DLB, PDD and cognitive impairment in Parkinson's disease (CIND-PD).
      DATA COLLECTION AND ANALYSIS: Data were extracted from published reports by one
      review author (MR). The data for each 'condition' (that is DLB, PDD or CIND-PD)
      were considered separately and, where possible, also pooled together. Statistical
      analysis was conducted using Review Manager version 5.0. MAIN RESULTS: Six trials
      met the inclusion criteria for this review, in which a total of 1236 participants
      were randomised. Four of the trials were of a parallel group design and two cross
      over trials were included. Four of the trials included participants with a
      diagnosis of Parkinson's disease with dementia (Aarsland 2002a; Dubois 2007; Emre
      2004; Ravina 2005), of which Dubois 2007 remains unpublished. Leroi 2004 included
      patients with cognitive impairment and Parkinson's disease (both with and without
      dementia). Patients with dementia with Lewy bodies (DLB) were included in only
      one of the trials (McKeith 2000).For global assessment, three trials comparing
      cholinesterase inhibitor treatment to placebo in PDD (Aarsland 2002a; Emre 2004;
      Ravina 2005) reported a difference in the Alzheimer's Disease Cooperative Study
      Clinical Global Impression of Change (ADCS-CGIC) score of -0.38, favouring the
      cholinesterase inhibitors (95% CI -0.56 to -0.24, P < 0.0001).For cognitive
      function, a pooled estimate of the effect of cholinesterase inhibitors on
      cognitive function measures was consistent with the presence of a therapeutic
      benefit (standardised mean difference (SMD) -0.34, 95% CI -0.46 to -0.23, P <
      0.00001). There was evidence of a positive effect of cholinesterase inhibitors on
      the Mini-Mental State Examination (MMSE) in patients with PDD (WMD 1.09, 95% CI
      0.45 to 1.73, P = 0.0008) and in the single PDD and CIND-PD trial (WMD 1.05, 95%
      CI 0.42 to 1.68, P = 0.01) but not in the single DLB trial.For behavioural
      disturbance, analysis of the pooled continuous data relating to behavioural
      disturbance rating scales favoured treatment with cholinesterase inhibitors (SMD 
      0.20, 95% CI -0.36 to -0.04, P = 0.01).For activities of daily living, combined
      data for the ADCS and the Unified Parkinson's Disease Rating Scale (UPDRS)
      activities of daily living rating scales favoured treatment with cholinesterase
      inhibitors (SMD -0.20, 95% CI -0.38 to -0.02, P = 0.03).For safety and
      tolerability, those taking a cholinesterase inhibitor were more likely to
      experience an adverse event (318/452 versus 668/842; odds ratio (OR) 1.64, 95% CI
      1.26 to 2.15, P = 0.0003) and to drop out (128/465 versus 45/279; OR 1.94, 95% CI
      1.33 to 2.84, P = 0.0006). Adverse events were more common amongst those taking
      rivastigmine (357/421 versus 173/240; OR 2.28, 95% CI 1.53 to 3.38, P < 0.0001)
      but not those taking donepezil (311/421 versus 145/212; OR 1.24, 95% CI 0.86 to
      1.80, P = 0.25). Parkinsonian symptoms in particular tremor (64/739 versus
      12/352; OR 2.71, 95% CI 1.44 to 5.09, P = 0.002), but not falls (P = 0.39), were
      reported more commonly in the treatment group but this did not have a significant
      impact on the UPDRS (total and motor) scores (P = 0.71). Fewer deaths occurred in
      the treatment group than in the placebo group (4/465 versus 9/279; OR 0.28, 95%
      CI 0.09 to 0.84, P = 0.03). AUTHORS' CONCLUSIONS: The currently available
      evidence supports the use of cholinesterase inhibitors in patients with PDD, with
      a positive impact on global assessment, cognitive function, behavioural
      disturbance and activities of daily living rating scales. The effect in DLB
      remains unclear. There is no current disaggregated evidence to support their use
      in CIND-PD.

PMID- 22419315
TI  - One-to-one dietary interventions undertaken in a dental setting to change dietary
      behaviour.
AB  - BACKGROUND: The dental care setting is an appropriate place to deliver dietary
      assessment and advice as part of patient management. However, we do not know
      whether this is effective in changing dietary behaviour. OBJECTIVES: To assess
      the effectiveness of one-to-one dietary interventions for all ages carried out in
      a dental care setting in changing dietary behaviour. The effectiveness of these
      interventions in the subsequent changing of oral and general health is also
      assessed. SEARCH METHODS: The following electronic databases were searched: the
      Cochrane Oral Health Group Trials Register (to 24 January 2012), the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue
      1), MEDLINE via OVID (1950 to 24 January 2012), EMBASE via OVID (1980 to 24
      January 2012), CINAHL via EBSCO (1982 to 24 January 2012), PsycINFO via OVID
      (1967 to 24 January 2012), and Web of Science (1945 to 12 April 2011). We also
      undertook an electronic search of key conference proceedings (IADR and ORCA
      between 2000 and 13 July 2011). Reference lists of relevant articles, thesis
      publications (Dissertations Abstracts Online 1861 to 2011) were searched. The
      authors of eligible trials were contacted to identify any unpublished work.
      SELECTION CRITERIA: Randomised controlled trials assessing the effectiveness of
      one-to-one dietary interventions delivered in a dental care setting. DATA
      COLLECTION AND ANALYSIS: Abstract screening, eligibility screening and data
      extraction decisions were all carried out independently and in duplicate by two
      review authors. Consensus between the two opinions was achieved by discussion, or
      involvement of a third review author. MAIN RESULTS: Five studies met the criteria
      for inclusion in the review. Two of these were multi-intervention studies where
      the dietary intervention was one component of a wider programme of prevention,
      but where data on dietary behaviour change were reported. One of the single
      intervention studies was concerned with dental caries prevention. The other two
      concerned general health outcomes. There were no studies concerned with dietary
      change aimed at preventing tooth erosion. In four out of the five included
      studies a significant change in dietary behaviour was found for at least one of
      the primary outcome variables. AUTHORS' CONCLUSIONS: There is some evidence that
      one-to-one dietary interventions in the dental setting can change behaviour,
      although the evidence is greater for interventions aiming to change
      fruit/vegetable and alcohol consumption than for those aiming to change dietary
      sugar consumption. There is a need for more studies, particularly in the dental
      practice setting, as well as greater methodological rigour in the design,
      statistical analysis and reporting of such studies.

PMID- 22419316
TI  - Oxygen therapy for pneumonia in adults.
AB  - BACKGROUND: Oxygen therapy is widely used in the treatment of lung diseases.
      However, the effectiveness of oxygen therapy as a treatment for pneumonia is not
      well known. OBJECTIVES: To determine the effectiveness and safety of oxygen
      therapy in the treatment of pneumonia in adults older than 18 years. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL)
      2011, Issue 4, part of The Cochrane Library, www.thecochranelibrary.com (accessed
      9 December 2011), which includes the Cochrane Acute Respiratory Infections
      Group's Specialised Register, MEDLINE (1948 to November week 3, 2011) and EMBASE
      (1974 to December 2011). SELECTION CRITERIA: Randomised controlled trials (RCTs)
      of oxygen therapy for adults with community-acquired pneumonia (CAP) and
      nosocomial (hospital-acquired) pneumonia (HAP or NP) in intensive care units
      (ICU). DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed
      abstracts and assessed data for methodological quality. MAIN RESULTS: Three RCTs
      met our inclusion criteria. The studies enrolled 151 participants with CAP or
      immunosuppressed patients with pulmonary infiltrates. Overall, we found that non
      invasive ventilation can reduce the risk of death in the ICU, odd ratio (OR)
      0.28, 95% confidence interval (CI) 0.09 to 0.88; endotracheal intubation, OR
      0.26, 95% CI 0.11 to 0.61; complications, OR 0.23, 95% CI 0.08 to 0.70; and
      shorten ICU length of stay, mean duration (MD) -3.28, 95% CI -5.41 to -1.61.Non
      invasive ventilation and standard oxygen supplementation via a Venturi mask were
      similar when measuring mortality in hospital, OR 0.54, 95% CI 0.11 to 2.68; two
      month survival, OR 1.67, 95% CI 0.53 to 5.28; duration of hospital stay, MD 
      1.00, 95% CI -2.05 to 0.05; and duration of mechanical ventilation, standard MD 
      0.26, 95% CI -0.66 to 0.14. Some outcomes and complications of non-invasive
      ventilation were varied according to different participant populations. We also
      found that some subgroups had a high level of heterogeneity when conducting
      pooled analyses. AUTHORS' CONCLUSIONS: Non-invasive ventilation can reduce the
      risk of death in the ICU, endotracheal intubation, shorten ICU stay and length of
      intubation. Some outcomes and complications of non-invasive ventilation were
      varied according to different participant populations. Other than the oxygen
      therapy, we must mention the importance of standard treatment by physicians. The
      evidence is weak and we did not include participants with pulmonary tuberculosis
      and cystic fibrosis. More RCTs are required to answer these clinical questions.
      However, the review indicates that non-invasive ventilation may be more
      beneficial than standard oxygen supplementation via a Venturi mask for pneumonia.

PMID- 22419317
TI  - Anti-inflammatory drugs and analgesics for managing symptoms in people with
      cystic fibrosis-related arthritis.
AB  - BACKGROUND: Arthritis remains a relatively infrequent complication of cystic
      fibrosis, but is a cause of significant morbidity when it does occur. Two
      distinct types of arthritis are described in cystic fibrosis: cystic fibrosis
      related arthropathy (CFA) and hypertrophic pulmonary osteoarthropathy (HPO).
      Management of arthritis in people with cystic fibrosis is uncertain and complex
      because of the underlying disease and its intense treatment. OBJECTIVES: To
      review the effectiveness and safety of pharmacological agents for the symptomatic
      management of cystic fibrosis-related arthritis in adults and children with
      cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and
      Genetic Disorders Group Trials Register which comprises references identified
      from comprehensive electronic database searches, handsearches of relevant
      journals and abstract books of conference proceedings.Date of most recent search:
      16 December 2011. SELECTION CRITERIA: Randomised controlled trials which compared
      the efficacy and safety of anti-inflammatory and analgesic agents (e.g. non
      steroidal anti-inflammatory agents, systemic corticosteroids, intra-articular
      corticosteroids) with each other, with no treatment or with placebo for CFA and
      HPO. DATA COLLECTION AND ANALYSIS: No relevant studies were identified. MAIN
      RESULTS: No studies were included in this review. AUTHORS' CONCLUSIONS: Although
      it is generally recognised that CFA may be episodic and resolve spontaneously,
      treatment with analgesics and anti-inflammatory agents may be needed. While this
      approach may be sufficient to manage symptoms, it is disappointing that no
      randomised controlled trials to rigorously evaluate these agents were found, nor
      could the authors identify any quasi-randomised. This systematic review has
      identified the need for a well-designed adequately-powered randomised controlled
      trial to assess the efficacy and safety of pharmacological agents for the
      symptomatic management of cystic fibrosis-related arthritis (CFA and HPO) in
      adults and children with cystic fibrosis. Studies should also better define the
      two conditions. A study has recently been conducted in CFA and may help fill this
      gap when analysed and published.There are no trials included in the review up to
      January 2012. We do not plan to update this review until new trials are
      published, although we will search the Group's Cystic Fibrosis Trials Register on
      a two-yearly cycle.

PMID- 22419318
TI  - Statins for age-related macular degeneration.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is a progressive late onset
      disorder of the macula affecting central vision. Age-related macular degeneration
      is the leading cause of blindness in people over 65 years in industrialized
      countries (Congdon 2003). Recent epidemiologic, genetic and pathological evidence
      has shown AMD shares a number of risk factors with atherosclerosis, leading to
      the hypothesis that statins may exert protective effects in AMD. OBJECTIVES: To
      examine the effectiveness of statins compared with other treatments, no
      treatment, or placebo in delaying the onset and/or progression of AMD. SEARCH
      METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group
      Trials Register) (The Cochrane Library 2011, Issue 9), MEDLINE (January 1950 to
      September 2011), EMBASE (January 1980 to September 2011), Latin American and
      Caribbean Health Sciences Literature Database (LILACS) (January 1982 to September
      2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com),
      ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical
      Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no
      date or language restrictions in the electronic searches for trials. The
      electronic databases were last searched on 16 September 2011. SELECTION CRITERIA:
      We included randomized controlled trials (RCTs) that compared statins with other
      treatments, no treatment, or placebo in participants who were either susceptible
      to or diagnosed as having early stages of AMD. DATA COLLECTION AND ANALYSIS: Two
      authors independently evaluated the search results against the selection
      criteria. Two Italian speaking colleagues extracted data. One author entered
      data. We did not perform a meta-analysis because only one completed RCT was
      identified. MAIN RESULTS: Two studies met the selection criteria. One trial
      reported insufficient details to assess the risk of bias; the other trial is
      ongoing.Of the completed trial, the analyses of 30 participants did not show a
      statistically significant difference between the simvastatin and the placebo arm
      in visual acuity at three months of treatment (decimal visual acuity 0.21+/- 0.56
      in simvastatin and 0.19+/- 0.40 in placebo arm) or 45 days after the completion
      of treatment (decimal visual acuity 0.20+/- 0.50 in simvastatin and 0.19+/- 0.48
      in placebo arm). The lens and retina status were unchanged during and after the
      treatment period for both groups.Of the ongoing trial, the preliminary analyses
      of 42 participants who completed 12 months follow-up did not show a statistically
      significant difference between the simvastatin and the placebo arm in visual
      acuity, drusen score or visual function (effect estimates and confidence
      intervals were not available). We contacted the investigators and will update the
      review as data become available. AUTHORS' CONCLUSIONS: Evidence from currently
      available RCTs was insufficient to conclude that statins have any role in
      preventing or delaying the onset or progression of AMD.

PMID- 22419319
TI  - Honey for acute cough in children.
AB  - BACKGROUND: Cough causes concern for parents and is a major cause of outpatient
      visits. It can impact on quality of life, cause anxiety and affect sleep in
      parents and children. Several remedies, including honey, have been used to
      alleviate cough symptoms. OBJECTIVES: To evaluate the effectiveness of honey for
      acute cough in children in ambulatory settings. SEARCH METHODS: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      Issue 4, 2011) which contains the Cochrane Acute Respiratory Infections Group's
      Specialised Register; MEDLINE (1950 to December week 4, 2011); EMBASE (1990 to
      January 2012); CINAHL (1981 to January 2012); Web of Science (2000 to January
      2012); AMED (1985 to January 2012); LILACS (1982 to January 2012); and CAB
      abstracts (2009 to January 2012). SELECTION CRITERIA: Randomised controlled
      trials (RCTs) comparing honey given alone, or in combination with antibiotics,
      versus nothing, placebo or other over-the-counter (OTC) cough medications to
      participants aged from two to 18 years for acute cough in ambulatory settings.
      DATA COLLECTION AND ANALYSIS: Two review authors independently screened search
      results for eligible studies and extracted data on reported outcomes. MAIN
      RESULTS: We included two RCTs of high risk of bias involving 265 children. The
      studies compared the effect of honey with dextromethorphan, diphenhydramine and
      'no treatment' on symptomatic relief of cough using the 7-point Likert
      scale.Honey was better than 'no treatment' in reducing frequency of cough (mean
      difference (MD) -1.07; 95% confidence interval (CI) -1.53 to -0.60; two studies;
      154 participants). Moderate quality evidence suggests honey did not differ
      significantly from dextromethorphan in reducing cough frequency (MD -0.07; 95% CI
      -1.07 to 0.94; two studies; 149 participants). Low quality evidence suggests
      honey may be slightly better than diphenhydramine in reducing cough frequency (MD
      -0.57; 95% CI -0.90 to -0.24; one study; 80 participants).Adverse events included
      mild reactions (nervousness, insomnia and hyperactivity) experienced by seven
      children (9.3%) from the honey group and two (2.7%) from the dextromethorphan
      group; the difference was not significant (risk ratio (RR) 2.94; 95% Cl 0.74 to
      11.71; two studies; 149 participants). Three children (7.5%) in the
      diphenhydramine group experienced somnolence (RR 0.14; 95% Cl 0.01 to 2.68; one
      study; 80 participants) but there was no significant difference between honey
      versus dextromethorphan or honey versus diphenhydramine. No adverse event was
      reported in the 'no treatment' group. AUTHORS' CONCLUSIONS: Honey may be better
      than 'no treatment' and diphenhydramine in the symptomatic relief of cough but
      not better than dextromethorphan. There is no strong evidence for or against the
      use of honey.

PMID- 22419320
TI  - Antioxidant supplements for prevention of mortality in healthy participants and
      patients with various diseases.
AB  - BACKGROUND: Our systematic review has demonstrated that antioxidant supplements
      may increase mortality. We have now updated this review. OBJECTIVES: To assess
      the beneficial and harmful effects of antioxidant supplements for prevention of
      mortality in adults. SEARCH METHODS: We searched The Cochrane Library, MEDLINE,
      EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings
      Citation Index-Science to February 2011. We scanned bibliographies of relevant
      publications and asked pharmaceutical companies for additional trials. SELECTION
      CRITERIA: We included all primary and secondary prevention randomised clinical
      trials on antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin
      E, and selenium) versus placebo or no intervention. DATA COLLECTION AND ANALYSIS:
      Three authors extracted data. Random-effects and fixed-effect model meta-analyses
      were conducted. Risk of bias was considered in order to minimise the risk of
      systematic errors. Trial sequential analyses were conducted to minimise the risk
      of random errors. Random-effects model meta-regression analyses were performed to
      assess sources of intertrial heterogeneity. MAIN RESULTS: Seventy-eight
      randomised trials with 296,707 participants were included. Fifty-six trials
      including 244,056 participants had low risk of bias. Twenty-six trials included
      215,900 healthy participants. Fifty-two trials included 80,807 participants with
      various diseases in a stable phase. The mean age was 63 years (range 18 to 103
      years). The mean proportion of women was 46%. Of the 78 trials, 46 used the
      parallel-group design, 30 the factorial design, and 2 the cross-over design. All
      antioxidants were administered orally, either alone or in combination with
      vitamins, minerals, or other interventions. The duration of supplementation
      varied from 28 days to 12 years (mean duration 3 years; median duration 2 years).
      Overall, the antioxidant supplements had no significant effect on mortality in a
      random-effects model meta-analysis (21,484 dead/183,749 (11.7%) versus 11,479
      dead/112,958 (10.2%); 78 trials, relative risk (RR) 1.02, 95% confidence interval
      (CI) 0.98 to 1.05) but significantly increased mortality in a fixed-effect model
      (RR 1.03, 95% CI 1.01 to 1.05). Heterogeneity was low with an I(2)- of 12%. In
      meta-regression analysis, the risk of bias and type of antioxidant supplement
      were the only significant predictors of intertrial heterogeneity. Meta-regression
      analysis did not find a significant difference in the estimated intervention
      effect in the primary prevention and the secondary prevention trials. In the 56
      trials with a low risk of bias, the antioxidant supplements significantly
      increased mortality (18,833 dead/146,320 (12.9%) versus 10,320 dead/97,736
      (10.6%); RR 1.04, 95% CI 1.01 to 1.07). This effect was confirmed by trial
      sequential analysis. Excluding factorial trials with potential confounding showed
      that 38 trials with low risk of bias demonstrated a significant increase in
      mortality (2822 dead/26,903 (10.5%) versus 2473 dead/26,052 (9.5%); RR 1.10, 95%
      CI 1.05 to 1.15). In trials with low risk of bias, beta-carotene (13,202
      dead/96,003 (13.8%) versus 8556 dead/77,003 (11.1%); 26 trials, RR 1.05, 95% CI
      1.01 to 1.09) and vitamin E (11,689 dead/97,523 (12.0%) versus 7561 dead/73,721
      (10.3%); 46 trials, RR 1.03, 95% CI 1.00 to 1.05) significantly increased
      mortality, whereas vitamin A (3444 dead/24,596 (14.0%) versus 2249 dead/16,548
      (13.6%); 12 trials, RR 1.07, 95% CI 0.97 to 1.18), vitamin C (3637 dead/36,659
      (9.9%) versus 2717 dead/29,283 (9.3%); 29 trials, RR 1.02, 95% CI 0.98 to 1.07),
      and selenium (2670 dead/39,779 (6.7%) versus 1468 dead/22,961 (6.4%); 17 trials,
      RR 0.97, 95% CI 0.91 to 1.03) did not significantly affect mortality. In
      univariate meta-regression analysis, the dose of vitamin A was significantly
      associated with increased mortality (RR 1.0006, 95% CI 1.0002 to 1.001, P =
      0.002). AUTHORS' CONCLUSIONS: We found no evidence to support antioxidant
      supplements for primary or secondary prevention. Beta-carotene and vitamin E seem
      to increase mortality, and so may higher doses of vitamin A. Antioxidant
      supplements need to be considered as medicinal products and should undergo
      sufficient evaluation before marketing.

PMID- 22419321
TI  - Off-pump versus on-pump coronary artery bypass grafting for ischaemic heart
      disease.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) is performed both without and
      with cardiopulmonary bypass, referred to as off-pump and on-pump CABG
      respectively. However, the preferable technique is unclear. OBJECTIVES: To assess
      the benefits and harms of off-pump versus on-pump CABG in patients with ischaemic
      heart disease. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) on The Cochrane Library (Issue 1, 2011), MEDLINE
      (OVID, 1950 to February 2011), EMBASE (OVID, 1980 to February 2011), Science
      Citation Index Expanded on ISI Web of Science (1970 to February 2011) and CINAHL
      (EBSCOhost, 1981 to February 2011) on 2 February 2011. No language restrictions
      were applied. SELECTION CRITERIA: Randomised clinical trials of off-pump versus
      on-pump CABG irrespective of language, publication status and blinding were
      selected for inclusion. DATA COLLECTION AND ANALYSIS: For statistical analysis of
      dichotomous data risk ratio (RR) and for continuous data mean difference (MD)
      with 95% confidence intervals (CI) were used. Trial sequential analysis (TSA) was
      used for analysis to assess the risk of random error due to sparse data and to
      multiple updating of accumulating data. MAIN RESULTS: Eighty-six trials (10,716
      participants) were included. Ten trials (4,950 participants) were considered to
      be low risk of bias. Pooled analysis of all trials showed that off-pump CABG
      increased all-cause mortality compared with on-pump CABG (189/5,180 (3.7%) versus
      160/5144 (3.1%); RR 1.24, 95% CI 1.01 to 1.53; P =.04). In the trials at low risk
      of bias the effect was more pronounced (154/2,485 (6.2%) versus 113/2,465 (4.6%),
      RR 1.35,95% CI 1.07 to 1.70; P =.01). TSA showed that the risk of random error on
      the result was unlikely. Off-pump CABG resulted in fewer distal anastomoses (MD 
      0.28; 95% CI -0.40 to -0.16, P <.00001). No significant differences in myocardial
      infarction, stroke, renal insufficiency, or coronary re-intervention were
      observed. Off-pump CABG reduced post-operative atrial fibrillation compared with
      on-pump CABG, however, in trials at low risk of bias, the estimated effect was
      not significantly different. AUTHORS' CONCLUSIONS: Our systematic review did not
      demonstrate any significant benefit of off-pump compared with on-pump CABG
      regarding mortality, stroke, or myocardial infarction. In contrast, we observed
      better long-term survival in the group of patients undergoing on-pump CABG with
      the use of cardiopulmonary bypass and cardioplegic arrest. Based on the current
      evidence, on-pump CABG should continue to be the standard surgical treatment.
      However, off-pump CABG may be acceptable when there are contraindications for
      cannulation of the aorta and cardiopulmonary bypass. Further randomised clinical
      trials should address the optimal treatment in such patients.

PMID- 22419322
TI  - Early versus late tracheostomy for critically ill patients.
AB  - BACKGROUND: Long-term mechanical ventilation is the most common situation where
      tracheostomy is indicated for patients in intensive care units (ICU). 'Early' and
      'late' tracheostomies are two categories of the timing of tracheostomy. The
      evidence on the advantages attributed to early over late tracheostomy is somewhat
      conflicting but includes shorter hospital stays and lower mortality rates.
      OBJECTIVES: To evaluate the effectiveness and safety of early (<= 10 days after
      intubation) versus late tracheostomy (> 10 days after intubation) in critically
      ill adult patients predicted to be on prolonged mechanical ventilation and with
      different clinical conditions. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 12);
      MEDLINE (via PubMed) (1966 to December 2010); EMBASE (via Ovid) (from 1974 to
      December 2010); LILACS (1986 to December 2010); PEDro (Physiotherapy Evidence
      Database) at www.pedro.fhs.usyd.edu.au (1999 to December 2010) and CINAHL (1982
      to December 2010). SELECTION CRITERIA: We included all randomized or quasi
      randomized controlled trials which compared early tracheostomy (two to10 days
      after intubation) against late tracheostomy (> 10 days after intubation) for
      critically ill adult patients expected to be on prolonged mechanical ventilation.
      There was no language restriction. DATA COLLECTION AND ANALYSIS: Two authors
      extracted data and conducted a quality assessment. Meta-analyses using the random
      effects model were conducted for mortality and pneumonia. MAIN RESULTS: We
      included four studies, with a high risk of bias, in which a total of 673 patients
      were randomized to either early or late tracheostomy. We could not pool data in a
      meta-analysis because of clinical, methodological and statistical heterogeneity
      between the included studies. There is no strong evidence for real differences
      between early and late tracheostomy in the primary outcome of mortality. In one
      study a statistically significant result favouring early tracheostomy was
      observed in the outcome measuring time spent on ventilatory support (mean
      difference (MD) -9.80 days, 95% CI -11.48 to -8.12, P < 0.001). AUTHORS'
      CONCLUSIONS: Updated evidence is of low quality, and potential differences
      between early and late tracheostomy need to be better investigated by means of
      randomized controlled trials. At present there is no specific information about
      any subgroup or individual characteristics potentially associated with better
      outcomes with either early or late tracheostomy.

PMID- 22419324
TI  - Techniques of flushing and reperfusion for liver transplantation.
AB  - BACKGROUND: Various techniques of flushing and reperfusion have been advocated to
      improve outcomes after liver transplantation. There is considerable uncertainty
      as to which method is superior. OBJECTIVES: To compare the benefits and harms of
      different methods of flushing and reperfusion during liver implantation in the
      transplant recipients. SEARCH METHODS: We searched the Cochrane Central Register
      of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and
      Science Citation Index Expanded until March 2011. SELECTION CRITERIA: We included
      all randomised clinical trials that were performed to compare different
      techniques of flushing and reperfusion during liver transplantation. DATA
      COLLECTION AND ANALYSIS: Two authors independently identified the trials and
      extracted the data. We analysed the data with both the fixed-effect model and the
      random-effects model using RevMan analysis. For each outcome we calculated the
      hazard ratio (HR), risk ratio (RR), rate ratio, mean difference (MD), or
      standardised mean difference (SMD) with 95% confidence intervals (CI) based on
      available case analysis. MAIN RESULTS: We included six trials involving 418
      patients for this review. The sample size in the trials varied from 30 to 131
      patients. Only one trial involving 131 patients was of low risk of bias for
      mortality. This trial was at high risk of bias for other outcomes. Four trials
      excluded patients who underwent liver transplantation for acute liver failure.
      All the trials included livers obtained from cadaveric donors. The remaining five
      trials were of high risk of bias for all outcomes. Liver transplantation was
      performed by the conventional method (caval replacement) in two trials and piggy
      back method (caval preservation) in one trial. The method of liver
      transplantation was not available in the remaining three trials. The comparisons
      performed included an initial hepatic artery flush versus initial portal vein
      flush; blood venting via inferior vena cava in addition to venting of storage
      fluid versus no blood venting; initial hepatic artery reperfusion versus initial
      portal vein reperfusion; simultaneous hepatic artery and portal vein reperfusion
      versus initial portal vein reperfusion; and retrograde inferior vena cava
      reperfusion versus simultaneous hepatic artery and portal vein reperfusion. Only
      one or two trials could be included under each comparison. There was no
      significant difference in mortality, graft survival, or severe morbidity rates in
      any of the comparisons. Quality of life was not reported in any of the trials.
      AUTHORS' CONCLUSIONS: There is currently no evidence to support or refute the use
      of any specific technique of flushing or reperfusion during liver
      transplantation. Due to the paucity of data, absence of evidence should not be
      confused with evidence of absence of any differences. Further well designed
      trials with low risk of systematic error and low risk of random errors are
      necessary.

PMID- 22419323
TI  - Routine preoperative medical testing for cataract surgery.
AB  - BACKGROUND: Cataract surgery is practiced widely and substantial resources are
      committed to an increasing cataract surgical rate in developing countries. With
      the current volume of cataract surgery and the increases in the future, it is
      critical to optimize the safety and cost-effectiveness of this procedure. Most
      cataracts are performed on older individuals with correspondingly high systemic
      and ocular comorbidities. It is likely that routine preoperative medical testing
      will detect medical conditions, but it is questionable whether these conditions
      should preclude individuals from cataract surgery or change their perioperative
      management. OBJECTIVES: (1) To investigate the evidence for reductions in adverse
      events through preoperative medical testing, and (2) to estimate the average cost
      of performing routine medical testing. SEARCH METHODS: We searched CENTRAL (which
      contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane
      Library 2011, Issue 12), MEDLINE (January 1950 to December 2011), EMBASE (January
      1980 to December 2011), Latin American and Caribbean Literature on Health
      Sciences (LILACS) (January 1982 to December 2011), the metaRegister of Controlled
      Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov
      (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry
      Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language
      restrictions in the electronic searches for trials. The electronic databases were
      last searched on 9 December 2011. We used reference lists and the Science
      Citation Index to search for additional studies. SELECTION CRITERIA: We included
      randomized clinical trials in which routine preoperative medical testing was
      compared to no preoperative or selective preoperative testing prior to age
      related cataract surgery. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed abstracts to identify possible trials for inclusion. For
      each included study, two review authors independently documented study
      characteristics, extracted data, and assessed methodological quality. MAIN
      RESULTS: The three randomized clinical trials included in this review reported
      results for 21,531 total cataract surgeries with 707 total surgery-associated
      medical adverse events, including 61 hospitalizations and three deaths. Of the
      707 medical adverse events reported, 353 occurred in the pretesting group and 354
      occurred in the no testing group. Most events were cardiovascular and occurred
      during the intraoperative period. Routine preoperative medical testing did not
      reduce the risk of intraoperative (OR 1.02, 95% CI 0.85 to 1.22) or postoperative
      medical adverse events (OR 0.96, 95% CI 0.74 to 1.24) when compared to selective
      or no testing. Cost savings were evaluated in one study which estimated the costs
      to be 2.55 times higher in those with preoperative medical testing compared to
      those without preoperative medical testing. There was no difference in
      cancellation of surgery between those with preoperative medical testing and those
      with no or limited preoperative testing, reported by two studies. AUTHORS'
      CONCLUSIONS: This review has shown that routine pre-operative testing does not
      increase the safety of cataract surgery. Alternatives to routine preoperative
      medical testing have been proposed, including self-administered health
      questionnaires, which could substitute for health provider histories and physical
      examinations. Such avenues may lead to cost-effective means of identifying those
      at increased risk of medical adverse events due to cataract surgery. However,
      despite the rare occurrence, adverse medical events precipitated by cataract
      surgery remain a concern because of the large number of elderly patients with
      multiple medical comorbidities who have cataract surgery in various settings. The
      studies summarized in this review should assist recommendations for the standard
      of care of cataract surgery, at least in developed settings. Unfortunately, in
      developing country settings, medical history questionnaires would be useless to
      screen for risk since few people have ever been to a physician, let alone been
      diagnosed with any chronic disease.

PMID- 22419325
TI  - Patient positioning (mobilisation) and bracing for pain relief and spinal
      stability in metastatic spinal cord compression in adults.
AB  - BACKGROUND: Many patients with metastatic spinal cord compression (MSCC) have
      spinal instability but are determined, by their clinician, to be unsuitable for
      surgical internal fixation due to their advanced disease. Mobilisation may be
      hazardous in the presence of spinal instability as further vertebral collapse can
      occur. Current guidance on positioning (or mobilisation) and spinal bracing is
      contradictory. OBJECTIVES: To investigate the correct positioning (or
      mobilisation) and examine the effects of spinal bracing to relieve pain or to
      prevent further vertebral collapse in patients with MSCC. SEARCH METHODS: The
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE,
      CINAHL, CANCERLIT, NICE, SIGN, AMED, TRIP, National Guideline Clearinghouse and
      PEDro database were searched; the last search was run in February 2012. SELECTION
      CRITERIA: We selected randomised controlled trials (RCTs) of adults with MSCC of
      interventions on positioning or mobilisation and bracing. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed each possible study for
      inclusion and quality. MAIN RESULTS: One thousand, six hundred and eleven
      potentially relevant studies were screened. No studies met the inclusion
      criteria. Many papers identified the importance of mobilisation but no RCTs have
      been undertaken. No RCTs of bracing in MSCC were identified. AUTHORS'
      CONCLUSIONS: There is lack of evidence based guidance around how to correctly
      position and when to mobilise patients with MSCC or if spinal bracing is an
      effective technique for reducing pain or improving quality of life. RCTs are
      required in this important area.

PMID- 22419326
TI  - Regular treatment with formoterol versus regular treatment with salmeterol for
      chronic asthma: serious adverse events.
AB  - BACKGROUND: An increase in serious adverse events with both regular formoterol
      and regular salmeterol in chronic asthma has been demonstrated in previous
      Cochrane reviews. OBJECTIVES: We set out to compare the risks of mortality and
      non-fatal serious adverse events in trials which have randomised patients with
      chronic asthma to regular formoterol versus regular salmeterol. SEARCH METHODS:
      We identified trials using the Cochrane Airways Group Specialised Register of
      trials. We checked manufacturers' websites of clinical trial registers for
      unpublished trial data and also checked Food and Drug Administration (FDA)
      submissions in relation to formoterol and salmeterol. The date of the most recent
      search was January 2012. SELECTION CRITERIA: We included controlled, parallel
      design clinical trials on patients of any age and with any severity of asthma if
      they randomised patients to treatment with regular formoterol versus regular
      salmeterol (without randomised inhaled corticosteroids), and were of at least 12
      weeks' duration. DATA COLLECTION AND ANALYSIS: Two authors independently selected
      trials for inclusion in the review and extracted outcome data. We sought
      unpublished data on mortality and serious adverse events from the sponsors and
      authors. MAIN RESULTS: The review included four studies (involving 1116 adults
      and 156 children). All studies were open label and recruited patients who were
      already taking inhaled corticosteroids for their asthma, and all studies
      contributed data on serious adverse events. All studies compared formoterol 12
      MUg versus salmeterol 50 MUg twice daily. The adult studies were all comparing
      Foradil Aerolizer with Serevent Diskus, and the children's study compared Oxis
      Turbohaler to Serevent Accuhaler. There was only one death in an adult (which was
      unrelated to asthma) and none in children, and there were no significant
      differences in non-fatal serious adverse events comparing formoterol to
      salmeterol in adults (Peto odds ratio (OR) 0.77; 95% confidence interval (CI)
      0.46 to 1.28), or children (Peto OR 0.95; 95% CI 0.06 to 15.33). Over a six-month
      period, in studies involving adults that contributed to this analysis, the
      percentages with serious adverse events were 5.1% for formoterol and 6.4% for
      salmeterol; and over a three-month period the percentages of children with
      serious adverse events were 1.3% for formoterol and 1.3% for salmeterol. AUTHORS'
      CONCLUSIONS: We identified four studies comparing regular formoterol to regular
      salmeterol (without randomised inhaled corticosteroids, but all participants were
      on regular background inhaled corticosteroids). The events were infrequent and
      consequently too few patients have been studied to allow any firm conclusions to
      be drawn about the relative safety of formoterol and salmeterol. Asthma-related
      serious adverse events were rare and there were no reported asthma-related
      deaths.

PMID- 22419328
TI  - Percutaneous endoscopic gastrostomy versus nasogastric tube feeding for adults
      with swallowing disturbances.
AB  - BACKGROUND: A number of conditions compromise the passage of food along the
      digestive tract. Nasogastric tube (NGT) feeding is a classic, time-proven
      technique, although its prolonged use can lead to complications such as lesions
      to the nasal wing, chronic sinusitis, gastro-oesophageal reflux, and aspiration
      pneumonia. Another method of infusion, percutaneous endoscopy gastrostomy (PEG),
      is generally used when there is a need for enteral nutrition for a longer time
      period. There is a high demand for PEG in patients with swallowing disorders,
      although there is no consistent evidence about its effectiveness and safety as
      compared to NGT. OBJECTIVES: To evaluate the effectiveness and safety of PEG as
      compared to NGT for adults with swallowing disturbances, by updating our previous
      Cochrane review. SEARCH METHODS: We searched The Cochrane Library, MEDLINE,
      EMBASE, and LILACS from inception to September 2011, as well as contacting main
      authors in the subject area. There was no language restriction in the search.
      SELECTION CRITERIA: We planned to include randomised controlled trials comparing
      PEG versus NGT for adults with swallowing disturbances or dysphagia and
      indications for nutritional support, with any underlying diseases. The primary
      outcome was intervention failure (e.g. feeding interruption, blocking or leakage
      of the tube, no adherence to treatment). DATA COLLECTION AND ANALYSIS: Review
      authors performed selection, data extraction and evaluation of methodological
      quality of studies. For dichotomous and continuous variables, we used risk ratio
      (RR) and mean difference (MD), respectively with the random-effects statistical
      model and 95% confidence interval (CI). We assumed statistical heterogeneity when
      I2 > 50%. MAIN RESULTS: We included nine randomised controlled studies. We did
      not identify new eligible studies published after our previous review literature
      search date (August 2009). Intervention failure occurred in 19/156 patients in
      the PEG group and 63/158 patients in the NGT group (RR 0.24, 95%CI 0.08 to 0.76,
      P = 0.01) in favour of PEG. There was no statistically significant difference
      between comparison groups in complications (RR 1.00, 95%CI 0.91 to 1.11, P =
      0.93). AUTHORS' CONCLUSIONS: PEG was associated with a lower probability of
      intervention failure, suggesting the endoscopic procedure is more effective and
      safe as compared to NGT. There is no significant difference of mortality rates
      between comparison groups, and pneumonia irrespective of underlying disease
      (medical diagnosis). Future studies should include previously planned and
      executed follow-up periods, the gastrostomy technique, and the experience of the
      professionals to allow more detailed subgroup analysis.

PMID- 22419327
TI  - Centralisation of services for gynaecological cancer.
AB  - BACKGROUND: Gynaecological cancers are the second most common cancers among
      women. It has been suggested that centralised care improves outcomes but
      consensus is lacking. OBJECTIVES: To assess the effectiveness of centralisation
      of care for patients with gynaecological cancer. SEARCH METHODS: We searched the
      Cochrane Gynaecological Cancer Group Trials Register, CENTRAL (The Cochrane
      Library, Issue 4, 2010), MEDLINE, and EMBASE up to November 2010. We also
      searched registers of clinical trials, abstracts of scientific meetings, and
      reference lists of included studies. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs), quasi-RCTs, controlled before-and-after studies,
      interrupted time series studies, and observational studies that examined
      centralisation of services for gynaecological cancer, and used multivariable
      analysis to adjust for baseline case mix. DATA COLLECTION AND ANALYSIS: Three
      review authors independently extracted data, and two assessed risk of bias. Where
      possible, we synthesised the data on survival in a meta-analysis. MAIN RESULTS:
      Five studies met our inclusion criteria; all were retrospective observational
      studies and therefore at high risk of bias.Meta-analysis of three studies
      assessing over 9000 women suggested that institutions with gynaecologic
      oncologists on site may prolong survival in women with ovarian cancer, compared
      to community or general hospitals: hazard ratio (HR) of death was 0.90 (95%
      confidence interval (CI) 0.82 to 0.99). Similarly, another meta-analysis of three
      studies assessing over 50,000 women, found that teaching centres or regional
      cancer centres may prolong survival in women with any gynaecological cancer
      compared to community or general hospitals (HR 0.91; 95% CI 0.84 to 0.99). The
      largest of these studies included all gynaecological malignancies and assessed
      48,981 women, so the findings extend beyond ovarian cancer. One study compared
      community hospitals with semi-specialised gynaecologists versus general hospitals
      and reported non-significantly better disease-specific survival in women with
      ovarian cancer (HR 0.89; 95% CI 0.78 to 1.01). The findings of included studies
      were highly consistent. Adverse event data were not reported in any of the
      studies. AUTHORS' CONCLUSIONS: We found low quality, but consistent evidence to
      suggest that women with gynaecological cancer who received treatment in
      specialised centres had longer survival than those managed elsewhere. The
      evidence was stronger for ovarian cancer than for other gynaecological
      cancers.Further studies of survival are needed, with more robust designs than
      retrospective observational studies. Research should also assess the quality of
      life associated with centralisation of gynaecological cancer care. Most of the
      available evidence addresses ovarian cancer in developed countries; future
      studies should be extended to other gynaecological cancers within different
      healthcare systems.

PMID- 22419329
TI  - Distal aortic perfusion during thoracoabdominal aneurysm repair for prevention of
      paraplegia.
AB  - BACKGROUND: During thoracoabdominal aortic aneurysm (TAAA) surgery, decreased
      spinal cord perfusion can result in neurological deficits such as paraplegia and
      paraparesis. Distal aortic perfusion, alone or in combination with other
      adjuncts, may counter the decrease in spinal cord perfusion and hence reduce the
      risk of spinal cord injury. OBJECTIVES: To determine the effectiveness of distal
      aortic perfusion with or without other adjuncts against other adjuncts without
      use of distal perfusion during TAAA surgery in reducing the risk of developing
      paraplegia and paraparesis. SEARCH METHODS: The Cochrane Peripheral Vascular
      Diseases Group Specialised Register (last searched 5 January 2012) and CENTRAL
      (Issue 4, 2011) were searched for publications describing randomised controlled
      trials of distal aortic perfusion during thoracoabdominal aortic aneurysm
      surgery. Reference lists of relevant studies were checked. SELECTION CRITERIA:
      Randomised or quasi-randomised controlled clinical trials of distal aortic
      perfusion during TAAA repair. DATA COLLECTION AND ANALYSIS: Studies identified
      for potential inclusion were independently assessed for inclusion by at least two
      authors, with excluded trials arbitrated by the third author. MAIN RESULTS: There
      were no randomised controlled trials identified. AUTHORS' CONCLUSIONS: Currently,
      there are no randomised controlled trials to support the role of distal aortic
      perfusion in TAAA surgery for prevention of neurological injury. However,
      randomised controlled trials are not always feasible based on ethical grounds.
      Observational studies suggest that distal aortic perfusion alone or in
      combination with other adjuncts, that is cerebrospinal fluid (CSF) drainage,
      reduces the rate of neurologic deficit across all types of TAAA; in particular
      making a striking difference in the rate of neurologic deficit following type II
      TAAA repair. In the absence of randomised controlled trials, we recommend a
      standardised approach to reporting through registry studies to strengthen the
      evidence base for distal aortic perfusion.

PMID- 22419330
TI  - Milnacipran for neuropathic pain and fibromyalgia in adults.
AB  - BACKGROUND: Milnacipran is a serotonin-norepinephrine reuptake inhibitor (SNRI)
      that is sometimes used to treat chronic neuropathic pain and fibromyalgia.
      OBJECTIVES: To evaluate the analgesic efficacy and adverse effects of milnacipran
      in the management of chronic neuropathic pain or fibromyalgia. SEARCH METHODS: We
      searched CENTRAL, MEDLINE, and EMBASE to 4th of January 2012, together with
      reference lists of retrieved papers and reviews. SELECTION CRITERIA: We included
      randomised, double-blind studies of eight weeks duration or longer, comparing
      milnacipran with placebo or another active treatment in chronic neuropathic pain
      or fibromyalgia. DATA COLLECTION AND ANALYSIS: We extracted efficacy and adverse
      event data, and two study authors examined issues of study quality independently.
      MAIN RESULTS: Five studies (4138 participants) were included, all of which were
      placebo-controlled, involved participants with fibromyalgia, and used titration
      to a target dose of 100 mg or 200 mg milnacipran. There were no other active
      comparators or studies in other neuropathic pain conditions. Study quality was
      generally good, although the imputation method used in analyses of the primary
      outcomes could overestimate treatment effect.Both doses of milnacipran provided
      moderate levels of pain relief to about 40% of those treated, compared to 30%
      with placebo, giving a number needed to treat of 8 to 10. Adverse events were
      common in both milnacipran (87%) and placebo (78%) groups, but serious adverse
      events (< 2%) did not differ between groups. Nausea and constipation were the
      most common events showing the greatest difference between groups (number needed
      to treat for an additional harmful outcome of 7 and 13 respectively, compared
      with placebo).Withdrawals for any reason were more common with milnacipran than
      placebo, and more common with 200 mg than 100 mg (NNH of 23 and 8.8 respectively,
      compared with placebo). This was largely driven by adverse event withdrawals,
      where the NNH compared with placebo was 14 for 100 mg, and 7.0 for 200 mg).
      Withdrawals due to lack of efficacy were more common with milnacipran than
      placebo but did not differ between doses (number needed to treat to prevent an
      additional unwanted outcome of 45 and 41 respectively). AUTHORS' CONCLUSIONS: The
      evidence available indicates that milnacipran 100 mg or 200 mg is effective for a
      minority in the treatment of pain due to fibromyalgia, providing moderate levels
      of pain relief (at least 30%) to about 40% of participants, compared with about
      30% with placebo. There were insufficient data to assess substantial levels of
      pain relief (at least 50%), and the use of last observation carried forward
      imputation may overestimate drug efficacy. Milnacipran is associated with
      increased adverse events and adverse event withdrawals, which were significantly
      greater for the higher dose. There were no data for the use of milnacipran for
      other chronic neuropathic pain conditions.

PMID- 22419331
TI  - Airway clearance techniques for chronic obstructive pulmonary disease.
AB  - BACKGROUND: Cough and sputum production are common in chronic obstructive
      pulmonary disease (COPD) and are associated with adverse clinical outcomes.
      Airway clearance techniques (ACTs) aim to remove sputum from the lungs, however
      evidence of their efficacy during acute exacerbations of COPD (AECOPD) or stable
      disease is unclear. OBJECTIVES: To assess the safety and efficacy of ACTs for
      individuals with AECOPD and stable COPD. SEARCH METHODS: We searched the Cochrane
      Airways Group Specialised Register of trials from inception to October 2011, and
      PEDro in October 2009. SELECTION CRITERIA: We included randomised parallel trials
      and randomised cross-over trials which compared an ACT to no treatment, cough or
      sham ACT in participants with investigator-defined COPD, emphysema or chronic
      bronchitis. DATA COLLECTION AND ANALYSIS: Two review authors independently
      conducted data extraction and assessed the risk of bias. We analysed data from
      studies of AECOPD separately from stable COPD, and classified the effects of ACTs
      as 'immediate' (less than 24 hours), 'short-term' (24 hours to eight weeks) or
      'long-term' (greater than eight weeks). One subgroup analysis compared the
      effects of ACTs that use positive expiratory pressure (PEP) to those that do not.
      MAIN RESULTS: Twenty-eight studies on 907 participants were included in the
      review. Study sample size was generally small (range 5 to 96 people) and overall
      quality was generally poor due to inadequate blinding and allocation procedures.
      Meta-analyses were limited by heterogeneity of outcome measurement and inadequate
      reporting of data.In people experiencing AECOPD, ACT use was associated with
      small but significant short-term reductions in the need for increased ventilatory
      assistance (odds ratio (OR) 0.21, 95% confidence interval (CI) 0.05 to 0.85; data
      from four studies on 171 people), the duration of ventilatory assistance (mean
      difference (MD) -2.05 days, 95% CI -2.60 to -1.51; mean duration for control
      groups seven days; data from two studies on 54 people) and hospital length of
      stay (MD -0.75 days, 95% CI -1.38 to -0.11; mean duration for control groups nine
      days; one study on 35 people). Data from a limited number of studies revealed no
      significant long-term benefits of ACTs on the number of exacerbations or
      hospitalisations, nor any short-term beneficial effect on health-related quality
      of life (HRQoL) as measured by the St. George's Respiratory Questionnaire (SGRQ)
      total score (MD -2.30, 95% CI -11.80 to 7.20; one study on 59 people).In people
      with stable COPD, data from single studies revealed no significant short-term
      benefit of ACTs on the number of people with exacerbations (OR 3.21, 95% CI 0.12
      to 85.20; one study on 30 people), significant short-term improvements in HRQoL
      as measured by the SGRQ total score (MD -6.10, 95% CI -8.93 to -3.27; one study
      on 15 people) and a reduced long-term need for respiratory-related
      hospitalisation (OR 0.27, 95% CI 0.08 to 0.95; one study on 35 participants).The
      magnitude of effect of PEP-based ACTs on the need for increased ventilatory
      assistance and hospital length of stay was greater than for non-PEP ACTs, however
      we found no statistically significant subgroup differences. There was one report
      of vomiting during treatment with postural drainage and head-down tilt. AUTHORS'
      CONCLUSIONS: Evidence from this review indicates that airway clearance techniques
      are safe for individuals with COPD and confer small beneficial effects on some
      clinical outcomes. Consideration may be given to the use of airway clearance
      techniques for patients with COPD in both acute and stable disease, however
      current studies suggest that the benefits achieved may be small.

PMID- 22419332
TI  - Tricyclic antidepressants for autism spectrum disorders (ASD) in children and
      adolescents.
AB  - BACKGROUND: Autism spectrum disorders (ASD) are a heterogeneous group of
      neurodevelopmental disorders, ranging in severity and characterised by early
      onset of delay and deviance in the development of social interaction, and verbal
      and nonverbal communication. ASD is associated with restricted and/or stereotyped
      interests or behaviours. Tricyclic antidepressants (TCAs) block noradrenaline and
      serotonin reuptake, increasing the availability of these neurotransmitters in the
      central nervous system. Via their impact on serotonin, TCAs have been used in the
      treatment of autistic symptoms and comorbidities in individuals with ASD.  
      OBJECTIVES: To determine if treatment with tricyclic antidepressants:1) improves
      the core features of autism, including restricted social interaction, restricted
      communication, and stereotypical and repetitive behaviours; 2) improves non-core
      features such as challenging behaviours; 3) improves comorbid states, such as
      depression and anxiety; 4) causes adverse effects. SEARCH METHODS: We ran the
      latest searches for this review on 23 May 2011. We searched: Cochrane Central
      Register of Controlled Trials (CENTRAL), 2011 Issue 2, MEDLINE (1948 to May Week
      2, 2011), EMBASE (1980 to 2011 Week 2), PsycINFO (1887 to current), CINAHL (1937
      to current). We also searched Dissertation Abstracts International via
      Dissertation Express, and the metaRegister of Controlled Trials. SELECTION
      CRITERIA: Randomised controlled trials of any dose, duration and frequency of
      oral TCAs compared with placebo, in children and adolescents with a diagnosis of
      ASD, where at least one standardised outcome measure had been used. DATA
      COLLECTION AND ANALYSIS: Two review authors independently selected and appraised
      the studies for inclusion and risk of bias. All data were continuous. MAIN
      RESULTS: Three studies met the inclusion criteria for this review. Two studies
      used clomipramine and one used tianeptine. All three trials were small, with
      between 12 and 32 participants. One of the clomipramine trials involved children
      and young adults, while the other two trials enrolled only children. Due to
      heterogeneity in study participant characteristics, the TCA medications
      investigated and the outcome measures used, we were not able to perform any meta
      analysis.In only one of the three studies was there any indication that giving
      children tianeptine could be effective in the short term. In this study, parents
      and teachers reported that it reduced irritability, hyperactivity, inadequate eye
      contact and inappropriate speech, but clinician ratings found no significant
      impact on these symptoms. There were also significant adverse effects, including
      increased drowsiness and reduced activity levels in these individuals while being
      treated with tianeptine. The evidence of the impact of clomipramine in the two
      studies is contradictory. There was evidence of improvement in autistic symptoms,
      irritability and obsessive-compulsive disorder type symptoms, but conflicting
      evidence in relation to hyperactivity across the two studies, and no significant
      changes found with inappropriate speech. There were also adverse effects reported
      with the use of clomipramine. Although side effect ratings were not significantly
      different to placebo, there were significant dropout rates in the clomipramine
      arm of one study. AUTHORS' CONCLUSIONS: Clinicians considering the use of TCAs
      need to be aware of the limited and conflicting evidence of effect and the side
      effect profile when discussing this treatment option with people who have ASD and
      their carers. Further research is required before TCAs can be recommended for
      treatment of individuals with ASD.

PMID- 22419333
TI  - Interventions for age-related visual problems in patients with stroke.
AB  - BACKGROUND: The prevalence of eye problems increases with age and, consequently,
      so does the level of visual impairment. As the incidence of stroke also increases
      with age, a significant proportion of stroke patients will have age-related
      visual problems. It is possible that the effect of interventions for age-related
      visual problems may differ in the population of stroke patients compared to the
      wider population of older people. The interaction between the problems arising
      directly from stroke and those arising directly from age-related visual problems
      will be complex. Interventions for age-related visual problems may also be
      affected by the presence of other stroke-related co-morbidities. Consequently,
      the nature and outcome of interventions for age-related visual problems may be
      different in patients with stroke. OBJECTIVES: The aim of this review is to
      determine if interventions for age-related visual problems improve functional
      ability following stroke. SEARCH METHODS: We searched the Cochrane Stroke Group
      Trials Register (March 2011), the Cochrane Eyes and Vision Group Trials Register
      (December 2009) and nine electronic bibliographic databases including: the
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue
      1), MEDLINE (1950 to February 2011), EMBASE (1980 to February 2011), CINAHL (1982
      to February 2011), AMED (1985 to February 2011) and PsycINFO (1967 to February
      2011). We also searched reference lists and trials registers, handsearched
      journals and conference proceedings, and contacted experts. SELECTION CRITERIA:
      Randomised trials in adults after stroke, where the intervention is specifically
      targeted at assessing, treating or correcting age-related visual problems, or
      improving the ability of the patient to cope with visual impairment. Primary
      outcome was functional ability in activities of daily living and secondary
      outcomes included functional ability in extended activities of daily living,
      visual acuity, visual field, visual function, balance, falls, depression and
      anxiety, discharge destination/residence after stroke, quality of life and social
      isolation, adverse events and death. DATA COLLECTION AND ANALYSIS: Two review
      authors independently screened abstracts and planned to extract data and appraise
      trials. We planned that assessment of methodological quality would be undertaken
      for allocation concealment, blinding of outcome assessor, method of dealing with
      missing data and other potential sources of bias. MAIN RESULTS: We considered
      7357 titles, 460 abstracts and 85 full papers. We identified no studies for
      inclusion in this review. AUTHORS' CONCLUSIONS: There are no implications for
      practice arising from this review. Evidence relating to the management of
      patients (from the general population) with age-related visual problems is
      available from other Cochrane reviews and is likely to be the best evidence
      available for making treatment decisions about individual patients. Subgroup
      analyses within these reviews to explore the effect of interventions for age
      related visual problems in patients with stroke are recommended. We recommend
      that the objectives and selection criteria for this Cochrane review are amended
      and clarified prior to any future updates.

PMID- 22419334
TI  - Mirror therapy for improving motor function after stroke.
AB  - BACKGROUND: Mirror therapy is used to improve motor function after stroke. During
      mirror therapy, a mirror is placed in the patient's midsagittal plane, thus
      reflecting movements of the non-paretic side as if it were the affected side.
      OBJECTIVES: To summarise the effectiveness of mirror therapy for improving motor
      function, activities of daily living, pain and visuospatial neglect in patients
      after stroke. SEARCH METHODS: We searched the Cochrane Stroke Group's Trials
      Register (June 2011), the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (1950 to June 2011),
      EMBASE (1980 to June 2011), CINAHL (1982 to June 2011), AMED (1985 to June 2011),
      PsycINFO (1806 to June 2011) and PEDro (June 2011). We also handsearched relevant
      conference proceedings, trials and research registers, checked reference lists
      and contacted trialists, researchers and experts in our field of study. SELECTION
      CRITERIA: We included randomised controlled trials (RCTs) and randomised cross
      over trials comparing mirror therapy with any control intervention for patients
      after stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently
      selected trials based on the inclusion criteria, documented the methodological
      quality of studies and extracted data. We analysed the results as standardised
      mean differences (SMDs) for continuous variables. MAIN RESULTS: We included 14
      studies with a total of 567 participants that compared mirror therapy with other
      interventions. When compared with all other interventions, mirror therapy may
      have a significant effect on motor function (post-intervention data: SMD 0.61;
      95% confidence interval (CI) 0.22 to 1.0; P = 0.002; change scores: SMD 1.04; 95%
      CI 0.57 to 1.51; P < 0.0001). However, effects on motor function are influenced
      by the type of control intervention. Additionally, mirror therapy may improve
      activities of daily living (SMD 0.33; 95% CI 0.05 to 0.60; P = 0.02). We found a
      significant positive effect on pain (SMD -1.10; 95% CI -2.10 to -0.09; P = 0.03)
      which is influenced by patient population. We found limited evidence for
      improving visuospatial neglect (SMD 1.22; 95% CI 0.24 to 2.19; P = 0.01). The
      effects on motor function were stable at follow-up assessment after six months.
      AUTHORS' CONCLUSIONS: The results indicate evidence for the effectiveness of
      mirror therapy for improving upper extremity motor function, activities of daily
      living and pain, at least as an adjunct to normal rehabilitation for patients
      after stroke. Limitations are due to small sample sizes of most included studies,
      control interventions that are not used routinely in stroke rehabilitation and
      some methodological limitations of the studies.

PMID- 22419335
TI  - Histamine H2-receptor antagonists for urticaria.
AB  - BACKGROUND: Urticaria is a common skin disease characterised by itching weals or
      hives, which can occur almost anywhere on the body. There are a number of
      different subtypes and a range of available treatment options. There is lack of
      agreement on the efficacy of H2-receptor antagonists used in the treatment of
      urticaria. OBJECTIVES: To assess the safety and effectiveness of H2-receptor
      antagonists in the treatment of urticaria. SEARCH METHODS: We searched the
      following databases up to 7 October 2011: the Cochrane Skin Group Specialised
      Register, CENTRAL in The Cochrane Library (2011, Issue 4), MEDLINE (from 2005),
      EMBASE (from 2007), and LILACS (from 1982). We also searched online trials
      registries for ongoing trials. SELECTION CRITERIA: Randomised controlled trials
      of H2-receptor antagonists in people with a clinical diagnosis of urticaria of
      any duration or of any subtype. Studies including H1-antihistamines for chronic
      urticaria are the topic of a separate Cochrane review; thus, they were not
      included in this review. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed trial quality and extracted and analysed data. MAIN
      RESULTS: Four studies of a relatively small size, involving 144 participants,
      were included in this review. A combination of ranitidine with diphenhydramine
      was more effective at improving the resolution of urticaria than diphenhydramine
      administered alone (risk ratio (RR) 1.59, 95% confidence interval (CI) 1.07 to
      2.36). Although there was a similar improvement in itching, weal size, and
      intensity, cimetidine provided no statistically significant greater overall
      improvement in symptoms of urticaria when compared to diphenhydramine. However, a
      combination of these medications was more effective than diphenhydramine alone
      (RR 2.02, 95% CI 1.03 to 3.94). Adverse events were reported with several of the
      interventions, i.e. ranitidine and diphenhydramine, causing drowsiness and
      sedation, but there was no significant difference in the level of sedation from
      baseline with either famotidine or diphenhydramine. AUTHORS' CONCLUSIONS: The
      very limited evidence provided by this review was based on a few old studies of a
      relatively small size, which we categorised as having high to unclear risk of
      bias. Thus, at present, the review does not allow confident decision-making about
      the use of H2-receptor antagonists for urticaria. Although some of these studies
      have reported a measure of relief of symptoms of urticaria and rather minimal
      clinical improvement in some of the participants, the evidence was weak and
      unreliable. We have emphasised the lack of precision and limitations in the
      reported data where appropriate in this review.

PMID- 22419336
TI  - Follow-up for improving psychological well being for women after a miscarriage.
AB  - BACKGROUND: Miscarriage is the premature expulsion of an embryo or fetus from the
      uterus up to 23 weeks of pregnancy and weighing up to 500 grams. International
      studies using diagnostic tools have identified that some women suffer from
      anxiety, depression and grief after miscarriage. Psychological follow-up might
      detect those women who are at risk of psychological complications following
      miscarriage. This review is necessary as the evidence is equivocal on the
      benefits of psychological follow-up after miscarriage. OBJECTIVES: Whether follow
      up affects the psychological well being of women following miscarriage. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (31 December 2011), reference lists of all retrieved papers and
      contacted professional and lay organisations to obtain any ongoing trials or
      unpublished data. SELECTION CRITERIA: Randomised controlled trials only. DATA
      COLLECTION AND ANALYSIS: All potential trials for eligibility according to the
      criteria specified in the protocol by screening the titles and abstracts,
      retrieving full reports of potentially relevant trials for assessment. All review
      authors extracted data and checked for accuracy. No studies were published in
      duplicate. When data were missing and only the abstract was available, we
      attempted to contact the trial authors. We resolved any disagreement through
      discussion. MAIN RESULTS: Six studies involving 1001 women were included. Three
      trials compared one counselling session with no counselling. There was no
      significant difference in psychological well being including anxiety, grief,
      depression avoidance and self-blame. One trial compared three one-hour
      counselling sessions with no counselling at four and 12 months. Some subscales
      showed statistical significance in favour of counselling and some in favour of no
      counselling. The results for two trials were given in narrative form as data were
      unavailable for meta-analyses. One trial compared multiple interventions. The
      other trial compared two counselling sessions with no counselling. Neither study
      favoured counselling. AUTHORS' CONCLUSIONS: Evidence is insufficient to
      demonstrate that psychological support such as counselling is effective post
      miscarriage. Further trials should be good quality, adequately-powered using
      standardised interventions and outcome measures at specific time points. The
      economic implications and women's satisfaction with psychological follow-up
      should also be explored in any future study.

PMID- 22419337
TI  - Memory Rehabilitation for people with multiple sclerosis.
AB  - BACKGROUND: Impairments in cognitive function, particularly memory, are common in
      patients with Multiple Sclerosis (MS) and these can potentially affect their
      ability to complete functional activities. There is evidence from single-case or
      small group studies that memory rehabilitation can be beneficial for patients
      with MS but findings from randomised controlled trials (RCTs) and systematic
      reviews have been inconclusive. OBJECTIVES: To determine the effectiveness of
      memory rehabilitation for patients with MS who have memory problems, and the
      effect of such interventions on functional abilities. SEARCH METHODS: We searched
      the Cochrane Multiple Sclerosis Group's Specialised Trials Register (last
      searched February 2011), and the following electronic databases: the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010,
      latest issue), NIHR Clinical Research Network database, MEDLINE (1966 to February
      2011), EMBASE (1980 to February 2011), CINAHL (1982 to April 2010), PsycINFO
      (1980 to February 2011), AMED (1985 to April 2010), British Nursing Index (1985
      to April 2010) and CAB Abstracts (1973 to April 2010). We handsearched relevant
      journals and reference lists. SELECTION CRITERIA: We selected RCTs of memory
      rehabilitation or cognitive rehabilitation for patients with MS in which a memory
      rehabilitation treatment group was compared to a control group. Selection was
      conducted independently first and confirmed through group discussion. Studies
      that included participants whose memory deficits were the result of conditions
      other than MS were excluded unless a subgroup of participants with MS with
      separate results could be identified. DATA COLLECTION AND ANALYSIS: Four
      reviewers were involved in study selection, quality assessment and data
      extraction. Investigators of primary studies were contacted for further
      information where required. Data analysis and synthesis were conducted in
      accordance with the Cochrane Handbook for Systematic Reviews of Interventions
      Version 5.1.0 [updated March 2011]. A 'best evidence' synthesis was performed
      based on the methodological quality of the primary studies included. MAIN
      RESULTS: Eight studies, involving 521 participants, were included. The
      interventions involved various memory retraining techniques, such as computerised
      programmes and training on internal and external memory aids. Control groups
      varied in format from assessment-only groups, discussion and games, non-specific
      cognitive retraining and attention or visuospatial training. The risk of bias of
      the included studies was generally low; three of the studies were evaluated to
      have high risk of bias related to certain aspects of their methodology. Meta
      analysis showed no significant effects of memory rehabilitation on memory
      function or functional abilities immediately or long-term. No significant effect
      of intervention was found, either immediately or long-term, on subjective reports
      of memory problems [Standard mean difference (SMD)  0.06 (95% confidence interval
      [CI] -0.21 to 0.34) and SMD 0.04 (95% CI -0.24 to 0.31)] respectively; on
      objective memory [SMD 0.24 (95% CI -0.02 to 0.49) and SMD 0.19 (95% CI -0.09 to
      0.47)]; on mood [SMD -0.04 (95% CI -0.26 to 0.17) and SMD 0.13 (95% CI -0.10 to
      0.36)]; and on Quality of Life [SMD -0.13 (95% CI -0.12 to 0.39) and SMD -0.11
      (95% CI -0.39 to 0.17)]. On Activities of Daily Living, no immediate treatment
      effect was observed [SMD -0.13 (95% CI -0.60 to 0.33)], but on long-term follow
      up the intervention group performed significantly worse than the control group
      [SMD -0.33 (95% CI -0.63 to -0.03)]. AUTHORS' CONCLUSIONS: There is no evidence
      to support the effectiveness of memory rehabilitation on memory function or
      functional abilities in patients with MS. However, this conclusion has been
      arrived because of the limited quality of some of the primary studies reviewed in
      this area. Further robust, RCTs of higher methodological quality and better
      quality of reporting are needed.

PMID- 22419338
TI  - Interventions for treating phosphorus burns.
AB  - BACKGROUND: Phosphorus burns are rarely encountered in usual clinical practice
      and occur mostly in military and industrial settings. However, these burns can be
      fatal, even with minimal burn area, and are often associated with prolonged
      hospitalisation. OBJECTIVES: To summarise the evidence of effects (beneficial and
      harmful) of all interventions for treating people with phosphorus burns. SEARCH
      METHODS: We searched the Cochrane Wounds Group Specialised Register (searched 30
      September 2011); the Cochrane Central Register of Controlled Trials (CENTRAL)
      (The Cochrane Library 2011, Issue 3); Ovid OLDMEDLINE (1947 to 1965); Ovid
      MEDLINE (1950 to September Week 3 2011); Ovid MEDLINE (In-Process & Other Non
      Indexed Citations 29 September 2011); Ovid EMBASE (1980 to 2011 Week 38); EBSCO
      CINAHL (1982 to 23 September 2011) and Conference Proceedings Citation Index -
      Science (CPCI-S) (1990 to 30 September 2011). SELECTION CRITERIA: Any comparisons
      of different ways of managing phosphorus burns including, but not restricted, to
      randomised trials. DATA COLLECTION AND ANALYSIS: We found two non-randomised
      comparative studies, both comparing patients treated with and without copper
      sulphate. MAIN RESULTS: These two comparative studies provide no evidence to
      support the use of copper sulphate in managing phosphorus burns. Indeed the small
      amount of available evidence suggests that it may be harmful. AUTHORS'
      CONCLUSIONS: First aid for phosphorus burns involves the common sense measures of
      acting promptly to remove the patient's clothes, irrigating the wound(s) with
      water or saline continuously, and removing phosphorus particles. There is no
      evidence that using copper sulphate to assist visualisation of phosphorus
      particles for removal is associated with better outcome, and some evidence that
      systemic absorption of copper sulphate may be harmful. We have so far been unable
      to identify any other comparisons relevant to informing other aspects of the care
      of patients with phosphorus burns. Future versions of this review will take
      account of information in articles published in languages other than English,
      which may contain additional evidence based on treatment comparisons.

PMID- 22419339
TI  - Calcineurin inhibitor minimisation versus continuation of calcineurin inhibitor
      treatment for liver transplant recipients.
AB  - BACKGROUND: The therapeutic success of liver transplantation has been largely
      attributable to the development of effective immunosuppressive treatment
      regimens. In particular, calcineurin inhibitors were essential in reducing acute
      rejection and improving early survival. Currently, more than 90% of all liver
      transplant recipients are treated with the calcineurin inhibitor cyclosporine or
      tacrolimus. Unfortunately, calcineurin inhibitors cause adverse events, such as
      nephrotoxicity, and because of this, minimisation (reduction and withdrawal)
      regimens of calcineurin inhibitor have been developed and studied. However, the
      benefits and harms of these minimisation regimens are unclear. OBJECTIVES: To
      assess the benefits and harms of calcineurin inhibitor minimisation for liver
      transplant recipients without substitution by another immunosuppressive agent.
      SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials
      Register (Gluud 2010), Cochrane Central Register of Controlled Clinical Trials
      (CENTRAL) in The Cochrane Library, MEDLINE (OvidSP), EMBASE (OvidSP), Science
      Citation Index Expanded (Royle 2003), and the World Health Organization (WHO)
      international clinical trials registry platform (www.who.int/ictrp) until August
      2011. In addition, we searched bibliographies of relevant articles as well as US
      Food and Drug Administration (FDA) and European Medicines Agency (EMA) drug
      approval reviews for additional trials. SELECTION CRITERIA: We planned to select
      all randomised clinical trials investigating calcineurin inhibitor reduction or
      withdrawal in liver transplant recipients, irrespective of blinding, publication
      status, or language. Quasi-randomised clinical studies and cohort studies that
      were obtained through the searches were considered only for the reporting of
      harms. Trials investigating substitution of one calcineurin inhibitor by another
      calcineurin inhibitor were excluded. Trials investigating calcineurin inhibitor
      withdrawal concurrently with switching over to a mammalian target of rapamycin
      (mTOR) inhibitor-based regimen (everolimus or sirolimus) or mycophenolate mofetil
      based regimen are the subject of a separate review. DATA COLLECTION AND ANALYSIS:
      Search strategies were used to obtain titles and abstracts of studies that were
      relevant for the review. Two authors independently scanned the references and
      assessed trial eligibility. MAIN RESULTS: A total of 1299 references were
      identified by the searches. After removal of duplicates, 794 references were
      left. Out of these, two abstract reports of one ongoing randomised trial
      fulfilled the inclusion criteria of the review. This ongoing trial studies total
      withdrawal of immunosuppression in patients who receive a calcineurin inhibitor
      (cyclosporine or tacrolimus) or mycophenolate mofetil as the only
      immunosuppressive agent. The trial compares withdrawal of calcineurin inhibitor
      or mycophenolate mofetil with continuation of calcineurin inhibitor or
      mycophenolate mofetil. However, no trial results on the outcomes of interest to
      this review were available. AUTHORS' CONCLUSIONS: This review shows that
      strategies regarding calcineurin inhibitor minimisation, that is, reduction or
      withdrawal, without substitution versus continuation of calcineurin inhibitor
      treatment lack evidence from randomised trials.More research with calcineurin
      inhibitor reduction and withdrawal regimens is needed to optimise dosing and
      timing of calcineurin inhibitor treatment in order to achieve optimal patient and
      graft survival with a minimum of adverse events.Specifically regarding
      calcineurin inhibitor reduction versus no reduction, we recommend that randomised
      trials evaluating calcineurin inhibitor reduction versus continuation of
      calcineurin inhibitor treatment are conducted.Regarding calcineurin inhibitor
      withdrawal, we recommend that mechanisms for tolerance and 'graft acceptance' are
      clarified, and patient groups likely to tolerate calcineurin inhibitor withdrawal
      are identified in order to select the right patients for total withdrawal of
      calcineurin inhibitors without substitution with another immunosuppressive drug.
      The randomised trials should only be performed in highly selected patients.

PMID- 22419340
TI  - Strategies for improving the acceptability and acceptance of the copper
      intrauterine device.
AB  - BACKGROUND: Intrauterine devices (IUDs) are highly effective and are the most
      widely used reversible contraceptive method in the world. However, in developed
      countries IUDs are among the least common methods of contraception used. We
      evaluated the effect of interventions to increase uptake of the copper IUD, a
      long-acting, reversible contraceptive method. OBJECTIVES: To determine
      effectiveness of interventions to improve uptake and continuation of the copper
      IUD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, PsycINFO, PubMed, ClinicalTrials.gov,
      International Clinical Trials Registry Platform (ICTRP) and OpenSIGLE. We also
      handsearched references of relevant reviews and included studies. SELECTION
      CRITERIA: We included randomised controlled trials (RCTs) and controlled before
      and after studies of interventions which measured use and uptake of contraception
      including copper IUD as an outcome. DATA COLLECTION AND ANALYSIS: Two authors
      independently screened the search results for relevant studies and extracted data
      from included studies. We used RevMan 5.1 to calculate Peto odd ratios (OR) with
      95% confidence intervals (CI) for dichotomous outcomes. We conducted meta
      analysis by pooling data for similar types of intervention where possible. We
      used the GRADE system to evaluate the quality of evidence. MAIN RESULTS: Nine
      studies representing 7960 women met our inclusion criteria, including seven
      randomised controlled trials and two controlled before and after studies that
      reported IUD uptake postintervention. We evaluated the quality of evidence as
      moderate to low. Three studies on contraceptive counselling and referrals by
      community workers showed an increase in uptake of the IUD among intervention
      groups (Peto OR 2.00; 95% CI 1.40 to 2.85). Two studies on antenatal
      contraceptive counselling also favoured the intervention groups (Peto OR 2.33;
      95% CI 1.39 to 3.91). One study on postnatal couple contraceptive counselling
      also showed an increase in IUD uptake compared to control (Peto OR 5.73; 95% CI
      3.59 to 9.15). The results of one study evaluating postnatal home visits and two
      studies on enhanced postabortion contraceptive counselling did not reach
      statistical significance. AUTHORS' CONCLUSIONS: Community-based interventions and
      antenatal contraceptive counselling improved uptake of copper IUD contraception.
      Since the copper IUD is one of the most effective reversible contraceptive
      methods, primary care and family planning and practitioners could consider
      adopting these interventions. Although our review suggests these interventions
      are clinically effective, a cost-benefit analysis may be required to evaluate
      applicability.

PMID- 22419341
TI  - Antibiotics prior to embryo transfer in ART.
AB  - BACKGROUND: Embryo transfer (ET) involves the placement of one or more embryos
      into the uterine cavity, usually by passing a catheter through the cervical os.
      ET is the final step in an assisted reproductive technology (ART) cycle, where a
      woman has undergone controlled ovarian stimulation, egg retrieval and in vitro
      fertilisation of her eggs. Despite the transfer of high quality embryos, many ETs
      do not result in a pregnancy. There are many factors which may affect the success
      of ET, including the presence of upper genital tract microbial colonisation. The
      administration of antibiotics prior to ET has been suggested as an intervention
      to reduce levels of microbial colonisation and hence improve pregnancy rates.
      OBJECTIVES: To evaluate the effectiveness and safety of antibiotic administration
      prior to ET during ART cycles. SEARCH METHODS: We searched the Menstrual
      Disorders and Subfertility Group Specialised Register, Cochrane Central Register
      of Controlled Trials (CENTRAL), The Cochrane Library, MEDLINE, Ovid MEDLINE(r) In
      Process & Other Non-Indexed Citations, Ovid MEDLINE(r) Daily and Ovid MEDLINE(r)
      (from inception to February 2011), Ovid EMBASE (January 2010 to February 2011),
      Ovid PsycINFO, CINAHL, LILACS, trial registers for ongoing and registered trials,
      citation indexes, ClinicalStudyResults, PubMed, OpenSIGLE database and for for
      herbal and complimentary therapy protocols and reviews. SELECTION CRITERIA: Only
      randomised controlled trials were included. DATA COLLECTION AND ANALYSIS: The
      titles and abstracts of articles identified by the search were screened by one
      review author for eligibility. Two review authors then independently examined the
      full text articles for suitability for inclusion in the review. Data were
      extracted independently by two review authors. MAIN RESULTS: We identified four
      potential studies, of which three were excluded.The included trial reported
      clinical pregnancy rates but not live births. There was no evidence of a
      difference in clinical pregnancy rate between those receiving an amoxycillin and
      clavulanic acid antibiotic combination (64/178: 36%) and those not (61/172:
      35.5%) (OR1.02, 95% CI 0.66 to 1.58). Genital tract colonisation was
      significantly reduced in women receiving this antibiotic regimen (OR 0.59, 95% CI
      0.37 to 0.95). AUTHORS' CONCLUSIONS: This review suggests that the administration
      of amoxycillin and clavulanic acid prior to embryo transfer reduced upper genital
      tract microbial contamination but did not alter clinical pregnancy rates. The
      effect of this intervention on live birth is unknown. There are no data from
      randomised controlled trials to support or refute other antibiotic regimens in
      this setting.Future research is warranted to assess the efficacy of alternative
      antibiotic regimens. Researchers should assess live birth as the primary outcome
      and address quantitative microbial colonization as a secondary outcome.

PMID- 22419342
TI  - Pain management for women in labour: an overview of systematic reviews.
AB  - BACKGROUND: The pain that women experience during labour is affected by multiple
      physiological and psychosocial factors and its intensity can vary greatly.  Most
      women in labour require pain relief. Pain management strategies include non
      pharmacological interventions (that aim to help women cope with pain in labour)
      and pharmacological interventions (that aim to relieve the pain of labour).
      OBJECTIVES: To summarise the evidence from Cochrane systematic reviews on the
      efficacy and safety of non-pharmacological and pharmacological interventions to
      manage pain in labour. We considered findings from non-Cochrane systematic
      reviews if there was no relevant Cochrane review. METHODS: We searched the
      Cochrane Database of Systematic Reviews (The Cochrane Library 2011, Issue 5), The
      Cochrane Database of Abstracts of Reviews of Effects (The Cochrane Library 2011,
      Issue 2 of 4), MEDLINE (1966 to 31 May 2011) and EMBASE (1974 to 31 May 2011) to
      identify all relevant systematic reviews of randomised controlled trials of pain
      management in labour. Each of the contributing Cochrane reviews (nine new, six
      updated) followed a generic protocol with 13 common primary efficacy and safety
      outcomes. Each Cochrane review included comparisons with placebo, standard care
      or with a different intervention according to a predefined hierarchy of
      interventions. Two review authors extracted data and assessed methodological
      quality, and data were checked by a third author. This overview is a narrative
      summary of the results obtained from individual reviews. MAIN RESULTS: We
      identified 15 Cochrane reviews (255 included trials) and three non-Cochrane
      reviews (55 included trials) for inclusion within this overview. For all
      interventions, with available data, results are presented as comparisons of: 1.
      Intervention versus placebo or standard care; 2. Different forms of the same
      intervention (e.g. one opioid versus another opioid); 3. One type of intervention
      versus a different type of intervention (e.g. TENS versus opioid). Not all
      reviews included results for all comparisons. Most reviews compared the
      intervention with placebo or standard care, but with the exception of opioids and
      epidural analgesia, there were few direct comparisons between different forms of
      the same intervention, and even fewer comparisons between different
      interventions. Based on these three comparisons, we have categorised
      interventions into: " What works" ,"What may work", and "Insufficient evidence to
      make a judgement".WHAT WORKSEvidence suggests that epidural, combined spinal
      epidural (CSE) and inhaled analgesia effectively manage pain in labour, but may
      give rise to adverse effects. Epidural, and inhaled analgesia effectively relieve
      pain when compared with placebo or a different type of intervention (epidural
      versus opioids). Combined-spinal epidurals relieve pain more quickly than
      traditional or low dose epidurals. Women receiving inhaled analgesia were more
      likely to experience vomiting, nausea and dizziness.When compared with placebo or
      opioids, women receiving epidural analgesia had more instrumental vaginal births
      and caesarean sections for fetal distress, although there was no difference in
      the rates of caesarean section overall. Women receiving epidural analgesia were
      more likely to experience hypotension, motor blockade, fever or urinary
      retention. Less urinary retention was observed in women receiving CSE than in
      women receiving traditional epidurals. More women receiving CSE than low-dose
      epidural experienced pruritus.  WHAT MAY WORKThere is some evidence to suggest
      that immersion in water, relaxation, acupuncture, massage and local anaesthetic
      nerve blocks or non-opioid drugs may improve management of labour pain, with few
      adverse effects.  Evidence was mainly limited to single trials. These
      interventions relieved pain and improved satisfaction with pain relief
      (immersion, relaxation, acupuncture, local anaesthetic nerve blocks, non-opioids)
      and childbirth experience (immersion, relaxation, non-opioids) when compared with
      placebo or standard care. Relaxation was associated with fewer assisted vaginal
      births and acupuncture was associated with fewer assisted vaginal births and
      caesarean sections.INSUFFICIENT EVIDENCEThere is insufficient evidence to make
      judgements on whether or not hypnosis, biofeedback, sterile water injection,
      aromatherapy, TENS, or parenteral opioids are more effective than placebo or
      other interventions for pain management in labour. In comparison with other
      opioids more women receiving pethidine experienced adverse effects including
      drowsiness and nausea.  AUTHORS' CONCLUSIONS: Most methods of non-pharmacological
      pain management are non-invasive and appear to be safe for mother and baby,
      however, their efficacy is unclear, due to limited high quality evidence. In many
      reviews, only one or two trials provided outcome data for analysis and the
      overall methodological quality of the trials was low. High quality trials are
      needed.There is more evidence to support the efficacy of pharmacological methods,
      but these have more adverse effects. Thus, epidural analgesia provides effective
      pain relief but at the cost of increased instrumental vaginal birth.It remains
      important to tailor methods used to each woman's wishes, needs and circumstances,
      such as anticipated duration of labour, the infant's condition, and any
      augmentation or induction of labour.A major challenge in compiling this overview,
      and the individual systematic reviews on which it is based, has been the
      variation in use of different process and outcome measures in different trials,
      particularly assessment of pain and its relief, and effects on the neonate after
      birth. This made it difficult to pool results from otherwise similar studies, and
      to derive conclusions from the totality of evidence. Other important outcomes
      have simply not been assessed in trials; thus, despite concerns for 30 years or
      more about the effects of maternal opioid administration during labour on
      subsequent neonatal behaviour and its influence on breastfeeding, only two out of
      57 trials of opioids reported breastfeeding as an outcome. We therefore strongly
      recommend that the outcome measures, agreed through wide consultation for this
      project, are used in all future trials of methods of pain management.

PMID- 22419343
TI  - Caffeine as an analgesic adjuvant for acute pain in adults.
AB  - BACKGROUND: Caffeine has been added to common analgesics such as paracetamol,
      ibuprofen, and aspirin, in the belief that it enhances analgesic efficacy.
      Evidence to support this belief is limited and often based on invalid
      comparisons. OBJECTIVES: To assess the relative efficacy in acute pain of a
      single dose of any analgesic plus caffeine against the same dose of analgesic
      alone. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, and the Oxford Pain
      Relief Database to January 2012, and also carried out Internet searches and
      contacted pharmaceutical companies known to have carried out trials that have not
      been published. SELECTION CRITERIA: We included randomised, double-blind studies
      that compared a single dose of analgesic plus caffeine with the same dose of the
      analgesic alone in the treatment of acute pain. DATA COLLECTION AND ANALYSIS: Two
      review authors independently assessed eligibility and quality of studies, and
      extracted data. Any disagreements or uncertainties were settled by discussion
      with a third review author. We sought any validated measure of analgesic
      efficacy, but particularly the number of participants experiencing at least 50%
      of the maximum possible pain relief over four to six hours, participants
      reporting a global evaluation of treatment of very good or excellent, or headache
      relief after two hours. We pooled comparable data to look for a statistically
      significant difference, and calculated numbers needed to treat to benefit (NNT)
      with caffeine. We also looked for any numerical superiority associated with the
      addition of caffeine, and information about any serious adverse events. MAIN
      RESULTS: We identified 19 studies (7238 participants) in valid comparisons. Most
      studies used paracetamol or ibuprofen, with 100 mg to 130 mg caffeine, and the
      most common pain conditions studied were postoperative dental pain, postpartum
      pain, and headache. There was a small but statistically significant benefit with
      caffeine used at doses of 100 mg or more, which was not dependent on the pain
      condition or type of analgesic. About 5% to 10% more participants achieve a good
      level of pain relief (at least 50% of the maximum) with the addition of caffeine,
      giving a NNT of about 15.Most comparisons individually demonstrated numerical
      superiority with caffeine, but not statistical superiority. One serious adverse
      event was reported with caffeine, but was considered unrelated to any study
      medication.We know or suspect of the existence of 20 additional studies with 9785
      participants for which data for analysis were not obtainable. The additional
      analgesic effect of caffeine remained statistically significant but clinically
      less important even if all the known missing data had no effect; that is not
      likely to be the case. AUTHORS' CONCLUSIONS: The addition of caffeine (>= 100 mg)
      to a standard dose of commonly used analgesics provides a small but important
      increase in the proportion of participants who experience a good level of pain
      relief.

PMID- 22419344
TI  - Micronutrient supplementation in pregnant women with HIV infection.
AB  - BACKGROUND: Micronutrient deficiencies are widespread and compound the effects of
      HIV disease; micronutrient supplements may be effective and safe in reducing this
      burden. OBJECTIVES: To assess whether micronutrient supplements are effective and
      safe in reducing mortality and morbidity in pregnant and lactating women with HIV
      infection and their infants. SEARCH METHODS: The review has been updated three
      times since publication in 2005. In reviews prior to this update (2011), we
      searched the CENTRAL, EMBASE, PubMed, and GATEWAY databases to identify
      randomised controlled trials of micronutrient supplements using the search
      methods of the Cochrane HIV/AIDS Group. In the 2011 review the PubMed, EMBASE,
      and CENTRAL databases were searched in July 2011. As the GATEWAY database does
      not include conference abstracts after 2006, we also searched the AIDS-specific
      conference database, www.aegis.org, and contacted researchers and organisations
      active in the field of research to identify additional unpublished trials.
      SELECTION CRITERIA: Randomised controlled trials were selected that compared the
      effects of micronutrient supplements (vitamins, trace elements, and combinations
      of these) with other supplements, placebo or no treatment on mortality,
      morbidity, pregnancy outcomes, immunologic indicators, and anthropometric
      measures in HIV-positive pregnant and lactating women. Any adverse effects of
      supplementation were recorded. DATA COLLECTION AND ANALYSIS: Two reviewer authors
      independently selected trials, appraised trial quality for risk of bias using
      standardised criteria, and extracted data using standardised forms. Where
      disagreements arose, a third author, acted as arbiter. MAIN RESULTS: One
      additional trial is included in this update in addition to the three trials
      included in the 2010 update of the initial Cochrane review. Four relatively
      large, well-conducted randomised controlled trials of the benefits of
      micronutrient supplementation have been conducted in pregnant and lactating women
      infected with HIV. Each of the trials evaluated a different micronutrient
      supplement and no direct comparisons or analyses can be made across the four
      trials. The four trials were conducted between 1995 and 2006. The trials have all
      been conducted by the same research team in Dar es Salaam in Tanzania, in an
      urban setting in hospital-based antenatal clinics. Pregnant women were recruited
      with gestational age ranging from 12 to 27 weeks in each of the trials. Sample
      sizes range from 400 to 1129 with a median of 1000 participants. Three of the
      trials were placebo-controlled. Different interventions have been evaluated in
      each trial, viz.:Vitamin A versus Vitamin A and multivitamins versus
      Multivitamins versus placebo; Selenium versus placebo; Zinc versus placebo; and
      Multiple RDA multivitamins versus Single RDA multivitamins. None of the women
      were receiving antiretrovrial therapy (ART).Multiple micronutrient supplements
      conferred multiple clinical benefits to pregnant women and their offspring. No
      significant adverse effects were reported.No significant clinical benefits were
      found from zinc supplementation of pregnant Tanzanian women.Selenium supplements
      given during and after pregnancy did not delay maternal HIV disease progression
      or improve pregnancy outcomes, but may improve child survival and decrease
      maternal diarrhoeal morbidity.There were no differences in maternal and infant
      outcomes when women received single RDA multivitamins or multiple RDA
      multivitamin supplementation.The evidence is lacking for the effects of
      micronutrient supplementation given concomitantly to pregnant women already
      initiated on antiretroviral therapy for treatment purposes.GRADE assessments were
      conducted on outcomes for each trial and included reviewing the data and the
      potential biases in each trial before grading the level of evidence. None of the
      trials were graded as providing high quality evidence primarily because there was
      no replication of results in other trials in other settings. AUTHORS'
      CONCLUSIONS: In keeping with previous World Health Organization (WHO)
      recommendations everything possible should be done to promote and support
      adequate dietary intake of micronutrients, while recognising that this may not be
      sufficient to correct specific micronutrient deficiencies in all HIV-infected
      individuals.Specific recommendations for pregnant and lactating women infected
      with HIV would be to include the provision of multivitamin supplements in single
      RDA formulations during the antenatal period and at least for 6 weeks post
      partum, especially for women who are breast-feeding.There is no conclusive
      evidence to provide stand-alone zinc or selenium supplementation to HIV-infected
      pregnant and lactating women.Micronutrient supplementation should not be used as
      a substitute for provision of recommended antiretroviral medication for
      preventing mother-to-child transmission of HIV and treating maternal HIV
      infection when this is recommended.Further trials of single supplements are
      required to build the evidence base. The long-term clinical benefits, adverse
      effects, and optimal formulation of multiple micronutrient supplements require
      further investigation in pregnant women at different stages of HIV infection.

PMID- 22419345
TI  - Mobile phone text messaging for promoting adherence to antiretroviral therapy in
      patients with HIV infection.
AB  - BACKGROUND: More than 34 million people are presently living with HIV infection.
      Antiretroviral therapy (ART) can help these people to live longer, healthier
      lives, but adherence to ART can be difficult. Mobile phone text-messaging has the
      potential to help promote adherence in these patients. OBJECTIVES: To determine
      whether mobile phone text-messaging is efficacious in enhancing adherence to ART
      in patients with HIV infection. SEARCH METHODS: Using the Cochrane
      Collaboration's validated search strategies for identifying randomised controlled
      trials and reports of HIV interventions, along with appropriate keywords and MeSH
      terms, we searched a range of electronic databases, including the Cochrane
      Central Register of Controlled Trials (CENTRAL), EMBASE, Literatura Latino
      Americana e do Caribe em Ciencias da Saude (LILACS), MEDLINE (via PubMed),
      PsycINFO, Web of Science, and the World Health Organization (WHO) Global Index
      Medicus. The date range was from  01 January 1980 to 01 November 2011. There were
      no limits to language or publication status. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) in which patients or their caregivers (in the case of
      infants and children) of any age, in any setting, and receiving ART were provided
      with mobile phone text messages as a means of promoting adherence to ART. DATA
      COLLECTION AND ANALYSIS: Two authors independently examined the abstracts of all
      identified trials. We initially identified 243 references. Seventeen full-text
      articles were closely reviewed. Both authors abstracted data independently, using
      a pre-designed, standardised data collection form. When appropriate, data were
      combined in meta-analysis. MAIN RESULTS: Two RCTs from Kenya were included in the
      review. One trial compared short weekly text messages against standard care. The
      other trial compared short daily, long daily, short weekly and long weekly
      messages against standard care. Both trials were with adult patients.In the trial
      comparing only short weekly messages to standard care, text messaging was
      associated with a lower risk of non-adherence at 12 months (RR 0.77, 95% CI 0.63
      to 0.93) and with the non-occurrence of virologic failure at 12 months (RR 0.83,
      95% CI 0.69 to 0.99).In the trial that compared different intervals and lengths
      for text-messaging to standard care, long weekly text-messaging was not
      significantly associated with a lower risk of non-adherence compared to standard
      care (RR 0.79, 95% CI 0.60 to 1.04). Patients receiving weekly text-messages of
      any length were at lower risk of non-adherence at 48 weeks than were patients
      receiving daily messages of any length (RR 0.79, 95% CI 0.64 to 0.99). There were
      no significant differences between weekly text-messaging of any length (RR 1.01,
      95% CI 0.75 to 1.37) and between short or long messaging at either interval (RR
      0.99, 95% CI 0.78 to 1.27). Compared to standard care, any daily text-messaging,
      whether short or long, did not reduce the risk for non-adherence (RR 0.99, 95% CI
      0.82 to 1.20).In meta-analysis of both trials, any weekly text-messaging (i.e.
      whether short or long messages) was associated with a lower risk of non-adherence
      at 48-52 weeks (RR 0.78, 95% CI 0.68 to 0.89). The effect of short weekly text
      messaging was also significant (RR 0.77, 95% CI 0.67 to 0.89). AUTHORS'
      CONCLUSIONS: There is high-quality evidence from the two RCTs that mobile phone
      text-messaging at weekly intervals is efficacious in enhancing adherence to ART,
      compared to standard care. There is high quality evidence from one trial that
      weekly mobile phone text-messaging is efficacious in improving HIV viral load
      suppression. Policy-makers should consider funding programs proposing to provide
      weekly mobile phone text-messaging as a means for promoting adherence to
      antiretroviral therapy. Clinics and hospitals should consider implementing such
      programs. There is a need for large RCTs of this intervention in adolescent
      populations, as well as in high-income countries.

PMID- 22419346
TI  - Strategic review of the Cochrane Library.

PMID- 22419347
TI  - The income elasticity of health care spending in developing and developed
      countries.
AB  - To date, international analyses on the strength of the relationship between
      country-level per capita income and per capita health expenditures have
      predominantly used developed countries' data. This study expands this work using
      a panel data set for 173 countries for the 1995-2006 period. We found that health
      care has an income elasticity that qualifies it as a necessity good, which is
      consistent with results of the most recent studies. Furthermore, we found that
      health care spending is least responsive to changes in income in low-income
      countries and most responsive to in middle-income countries with high-income
      countries falling in the middle. Finally, we found that 'Voice and
      Accountability' as an indicator of good governance seems to play a role in
      mobilizing more funds for health.

PMID- 22419348
TI  - Complications in brief: meniscus repair.

PMID- 22419349
TI  - Closed medical negligence claims can drive patient safety and reduce litigation.
AB  - BACKGROUND: Medical liability reform is viewed by many physician groups as a
      means of reducing medical malpractice litigation and lowering healthcare costs.
      However, alternative approaches such as closed medical negligence claims data may
      also achieve these goals. QUESTIONS/PURPOSES: We asked whether information
      gleaned from closed claims related to medical negligence could promote patient
      safety and reduce costs related to medical liability. Specifically, we
      investigated whether physician groups have examined such data to identify error
      patterns and to then institute specific patient treatment protocols. METHODS: We
      searched for medical societies that have systematically examined closed medical
      negligence claims in their specialty to develop specific standards of physician
      conduct. We then searched the medical literature for published evidence of the
      efficacy, if any, related to the patient safety measures thus developed. RESULTS:
      Anesthesia and obstetric physician societies have successfully targeted costs and
      related concerns arising from medical malpractice lawsuits by using data from
      closed claims to develop patient safety and treatment guidelines. In both
      specialties, after institution of safety measures derived from closed medical
      negligence claims, the incidence and costs related to medical malpractice
      decreased and physician satisfaction improved. CONCLUSIONS: Tort reform, in the
      form of legislatively prescribed limits on damages arising from lawsuits, is not
      the only means of addressing the incidence and costs related to medical
      malpractice litigation. As the experience of anesthesia and obstetric physicians
      has demonstrated, safety guidelines derived from analyzing past medical
      malpractice litigation can achieve the same goals while also promoting patient
      safety.

PMID- 22419351
TI  - Ultrastructural evaluation of enamel after dental bleaching associated with
      fluoride.
AB  - This study evaluated the effects on human enamel after two bleaching procedures:
      with a fluoridated bleaching agent and with topical fluoride application
      postbleaching. It used 43 enamel blocks (3 mm(2) ) that were ground flat (600
      2,000 grit) and polished with polishing paste (one and one-fourth). Specimens
      were randomly divided into three groups according to the bleaching procedure: (1)
      control group, (2) hydrogen peroxide 35% (HPF) and topical application of
      fluoride 1.23%, and (3) HP 38% (OP) with fluoride in its composition. Bleaching
      agents were used according to the manufacturer's instructions. Three
      methodologies were used: nanoindentation, to observe surface hardness and elastic
      modulus; atomic force microscopy, to observe surface roughness (R(a) - R(z)); and
      scanning electron microscopy, to observe the enamel surface effects. Group OP had
      a decrease in the elastic modulus after bleaching, which was recovered at 14
      days. An increased roughness (R(a); 32%) was observed on group HPF and had an
      increased erosion on enamel surface (67%). It was concluded that topical
      application of fluoride, after using the nonfluoridated whitening agent,
      increased the roughness values and erosion of enamel.

PMID- 22419350
TI  - Most effective regimen of tranexamic acid in knee arthroplasty: a prospective
      randomized controlled study in 240 patients.
AB  - BACKGROUND: The antifibrinolytic tranexamic acid reduces surgical blood loss, but
      studies have not identified an optimal regimen. QUESTIONS/PURPOSES: We studied
      different dosages, timings, and modes of administration to identify the most
      effective regimen of tranexamic acid in achieving maximum reduction of blood loss
      in TKA. METHODS: We prospectively studied five regimens (four intravenous, one
      local; 40 patients each) with a control group (no tranexamic acid). The four
      intravenous (10-mg/kg dose) regimens included (1) intraoperative dose (IO) given
      before tourniquet deflation, (2) additional preoperative dose (POIO), (3)
      additional postoperative dose (IOPO), and (4) all three doses (POIOPO). The fifth
      regimen was a single local application (LA). Two independent parameters of drain
      loss and total blood loss, calculated by the hemoglobin balance method, were
      evaluated statistically. RESULTS: Both parameters were reduced in all five
      regimens as against the control. A significant reduction in drain loss was seen
      in the POIO, IOPO, and POIOPO groups whereas total blood loss was significantly
      reduced in the POIO, POIOPO, and LA groups. The POIOPO group had the least drain
      loss (303 mL) and least total blood loss (688 mL). The IO group had the greatest
      drain loss and the IOPO group the greatest total blood loss. CONCLUSIONS: Single
      dose tranexamic acid did not give effective results. The two-dose regimen of POIO
      was the least amount necessary for effective results. When compared against the
      control, this regimen produced reduction of drain loss and total blood loss,
      whereas the IOPO regimen did not. The three-dose regimen of POIOPO produced
      maximum effective reduction of drain loss and total blood loss.

PMID- 22419352
TI  - A facile synthesis of PLGA encapsulated cerium oxide nanoparticles: release
      kinetics and biological activity.
AB  - In the present article a facile synthesis of cerium oxide nanoparticles (CNPs)
      encapsulated in PLGA microparticles is reported. The release kinetics of the CNPs
      from the PLGA matrix was investigated under acidic, basic and near-neutral pH. A
      diffusion model was applied to determine the diffusivity of the CNPs from the
      PLGA matrix. The morphology of the degraded PLGA particles was characterized by
      high resolution SEM. Superoxide dismutase (SOD) mimetic activity was retained in
      released CNPs for a longer period of time (~90 days) under different pH. PLGA
      encapsulated CNP showed excellent biocompatibility. This study demonstrates a
      potential strategy to deliver CNPs using biodegradable PLGA that ensures a slow
      release of the CNPs over a long period of time. Thus, the synthesized PLGA
      encapsulated CNPs could find potential applications in tissue engineering like
      bone remodelling and regeneration, and protection from disorders caused by
      neurodegeneration.

PMID- 22419353
TI  - Use of preoperative prolapse reduction stress testing and the risk of a second
      surgery for urinary symptoms following laparoscopic sacral colpoperineopexy.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to determine the
      reoperation rate for sling placement or revision in patients who had primary
      continence procedures based on prolapse reduction stress testing (RST) prior to
      laparoscopic sacral colpoperineopexy (LSCP). METHODS: This was a retrospective
      cohort study of women who had RST prior to LSCP for symptomatic pelvic organ
      prolapse. Patients with positive test (Pos RST) had a concomitant midurethral
      sling procedure and those with negative test (Neg RST) did not. Variables were
      compared with either Student's t test or Fisher's exact test. RESULTS: In Neg RST
      group (n = 70), the rate of surgery for de novo urodynamic stress incontinence
      was 18.6%. In Pos RST group (n = 82), the rate of sling revision for bladder
      outlet obstruction was 7.3%. Overall, 88% of patients did not require a second
      surgery. CONCLUSIONS: The use of RST to recommend concomitant continence
      procedures during LSCP results in a single surgery for the majority of our
      patients.

PMID- 22419354
TI  - Single-incision apical and posterior mesh repair: 1-year prospective outcomes.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this study was to assess the safety
      and efficacy of the Elevate Apical and Posterior single-incision mesh system
      (SIMS) with IntePro Lite for pelvic organ prolapse repair. METHODS: This
      prospective multicenter study included 139 women with >= stage II posterior
      vaginal prolapse and/or apical descent who underwent placement of type I
      polypropylene mesh through a single transvaginal incision with no external needle
      passes. Primary endpoint was the percent of patients with posterior and/or apical
      stage <= I ("cure") at follow-up. Secondary endpoints included, but were not
      limited to, rate of mesh extrusion and disease-specific quality of life outcomes.
      RESULTS: At 12 months, objective posterior wall and apical cure rates were 92.5
      and 89.2 %, respectively, with an extrusion rate of 6.5 %. CONCLUSIONS: The SIMS
      appears to be effective and safe in treating patients with posterior vaginal
      and/or apical prolapse. The risks and benefits of transvaginal synthetic mesh
      insertion should be considered.

PMID- 22419355
TI  - What are the causes and consequences of bladder overdistension? ICI-RS 2011.
AB  - AIMS: To report the outcome of the think tank on prolonged bladder overdistension
      from the 3rd ICI-RS meeting. METHODS: Prolonged bladder overdistension was
      discussed after acute urinary retention, its terminology, its prevalence,
      pathophysiology, and consequences, as well as prophylactic and therapeutic
      aspects. RESULTS: Acute prolonged bladder overdistension (ApBO) is a consequence
      of undetected or inadequately treated acute retention, and is mostly due to
      regional anesthesia, prolonged childbirth, or extensive surgery. Currently, there
      is no agreed terminology. A primary, temporary neurogenic detrusor dysfunction
      causing retention is associated with decreased or absent bladder sensation
      therefore patients do not complain, and management is delayed. Therapeutically,
      the first intervention is to drain the bladder. Recovery depends on whether
      reversible or irreversible damage has occurred. There are no good data to support
      the use of drugs or sacral neuromodulation. Intravesical electrostimulation is
      the only treatment that has specifically addressed this problem with encouraging
      results. There are no recent reports on the effect of surgery for myogenic
      bladder damage. CONCLUSION: ApBO is an important, but often unrecognized medical
      complication. There is a need for defining the terminology, for studies to record
      the incidence of different types of bladder overdistension, and to establish
      management strategies. Apart from clean intermittent self catheterization (CIC)
      there are no data justifying pharmacological or other therapies. Therefore,
      prevention is of paramount importance and there is a need to develop and test
      preventative strategies, which should then be incorporated in surgical
      registries.

PMID- 22419356
TI  - Measurement of solar UV radiation in Antarctica with collagen sheets.
AB  - Collagen sheets were used in a unique evaluation method to examine skin damage
      caused by ultraviolet (UV) light of short wavelength during a season of the
      Antarctic ozone hole. The collagen sheets were exposed outdoors for 25 and 50 d,
      in the spring when the ozone hole was formed and in the ozone-hole-free autumn.
      Extracts from the exposed collagen sheets were analyzed for total protein and
      terminal amino acid concentrations as an index of collagen fragmentation. The
      results show that the amount of extractable collagen and terminal amino acid
      concentration in the spring exposure were approximately double and five times
      higher, respectively, when compared with those in the autumn exposure. During the
      ozone hole occurrence, the terminal amino acid concentration of the extracted
      collagen was about five times higher when exposure lasted 50 d from mid-September
      to the end of October compared to when exposure lasted 25 d from mid-September to
      early October. This result could be attributed to a limited amount of short
      wavelength UV radiation reaching the ground surface as a result of the low height
      of the sun in September, when the ozone hole occurred. In fact, UV radiation
      measurements taken at Syowa Station indicate that short-wavelength UV radiation
      in the range 290-295 nm was not detected until approximately 1-2 months after the
      beginning of the ozone hole occurrence.

PMID- 22419357
TI  - Tetrasomy 13q31.1qter due to an inverted duplicated neocentric marker chromosome
      in a fetus with multiple malformations.
AB  - Small supernumerary marker chromosome (sSMC) lacking alpha satellite DNA or
      endogenous centromere regions are rare and contain fully functional centromeres,
      called neocentromeres. We report on a woman with a 14-week gestation pregnancy
      with a cystic hygroma and cerebellar hypoplasia at ultrasound examination.
      Cytogenetic studies showed a karyotype 47,XY,+mar dn. This sSMC was observed in
      chorionic villi, lung, and muscle tissue. Array Comparative Genomic Hybridization
      showed a gain from 13q31.1 to 13qter region. Fluorescent in situ hybridization
      with pan alpha satellite probe and probes specific for chromosome 13 showed a
      marker corresponding to an inversion duplication of the 13q distal chromosomal
      region without alpha satellite DNA sequence, suggesting the presence of a
      neocentromere. Examination of the fetus showed dysmorphic features, cystic
      cervical hygroma, postaxial polydactyly of the right hand and left foot with
      short fingers, malrotation of the gut, and a micropenis with hypospadias.
      Genotype-phenotype correlation in tetrasomy 13q is discussed according to the
      four 13q chromosomal breakpoints reported (13q32, 13q31, 13q21, 13q14) for
      chromosome 13 supernumerary markers.

PMID- 22419359
TI  - Electrochemical fluorination using alkali-metal fluorides.

PMID- 22419358
TI  - The use of three-dimensional rotational angiography to assess the pulmonary
      circulation following cavo-pulmonary connection in patients with single
      ventricle.
AB  - BACKGROUND: Bi-plane angiography is the gold standard for imaging the pulmonary
      arteries (PAs) after cavo-pulmonary connection (CPC). Three-dimensional
      rotational angiography (3DRA) is emerging technology that we hypothesized may
      enhance diagnostic capabilities in this patient group. METHODS: Retrospective
      review of patients who underwent 3DRA to assess the PAs after CPC. 3DRA images
      were examined for diagnostic quality and compared, both qualitatively and
      quantitatively with corresponding 2D images. RESULTS: Between 1/2010 and 12/2010,
      37 3DRAs were obtained in 32 pts with prior CPC. Median age and weight were 4.3
      years (0.3-19) and 15.7 kg (4.3-114). Previous surgery included: bi-directional
      Glenn (16), bilateral bi-directional Glenn (2), and Fontan (14). Thirty-three
      (89%) acquisitions in 28 pts were of diagnostic quality. In 19/28 pts (68%) 3DRA
      provided significant additional information pertaining to 22 lesions when
      compared with bi-plane angiography. These included delineating the mechanism of
      PA stenosis in 13 (aortic compression: 7, PA torsion: 6), demonstrating a
      discrete PA stenosis not seen or under appreciated on corresponding 2D images in
      9. This additional information led to the performance of 9 interventions (stent
      implantation 8, angioplasty 1). Corresponding 2D and 3DRA images of the right and
      left PA were compared using quantitative analysis with a correlation coefficient
      of 0.94 (P < 0.001) and 0.97 (P < 0.001), for the right and left PAs
      respectively. CONCLUSIONS: 3DRA can be performed safely and effectively following
      CPC and may be more sensitive in diagnosing PA stenoses than 2D angiography.
      Quantitative measurements of PA diameter using 3DRA correlates well with 2D
      angiography.

PMID- 22419360
TI  - Development of star polymers as unimolecular containers for nanomaterials.
AB  - Star polymers containing one central core surrounded by multiple radiating arms
      represent an intriguing type of globular platform to be used as unimolecular
      containers and reactors. The core domain can encapsulate guest "cargos", whereas
      protective shell and chain ends can be functionalized with reactive groups and
      ligands. This Feature Article highlights the recent development on using core
      shell structured amphiphilic star polymers as unimolecular containers for
      applications in drug delivery, catalysis, and template of hybrid nanomaterials.
      As compared with dendrimers, star polymers enjoy advantages of facile synthesis,
      flexible compositions, and tunable sizes, which allow them being able to carry
      more and multiple "cargos" within one molecule.

PMID- 22419361
TI  - Half-metallic carbon nanotubes.
AB  - Half-metallicity in carbon nanotubes is achieved and controlled by hydrogen
      adsorption patterns. The edge states in carbon nanotubes are unstable under an
      electric field due to the spin-conserving electron transfer between the edges,
      but a large enough transfer barrier between the edge states, obtained by
      controlling the adsorption patterns, renders the CNTs half-metallic.

PMID- 22419362
TI  - Steroid-resistant nephrotic syndrome associated with steroid sulfatase deficiency
      x-linked recessive ichthyosis: a case report and review of literature.
AB  - Nephrotic syndrome associated with X-linked recessive ichthyosis due to steroid
      sulfatase deficiency has rarely been reported in English literature. We describe
      a 4 and a half-year-old boy presenting with steroid-resistant nephrotic syndrome
      (SRNS) with an underlying ichthyotic skin present since birth. Renal biopsy
      revealed minimal change disease. As many of the male members of the family also
      showed similar skin manifestations, genetic analysis was done on the patient,
      which revealed deletion of the steroid sulfatase (STS) gene spanning both the 3'
      as well as the 5'ends. The patient was thus diagnosed with SRNS associated with X
      linked recessive ichthyosis. He was started on cyclosporine regimen, and
      remission was achieved in 5 weeks. We speculate that the deficiency of STS
      resulting in increased cholesterol sulfate accumulation interferes with the
      integrity of adherens junctions present between glomerular epithelial cells of
      the slit diaphragm, and this results in proteinuria and nephrotic syndrome. The
      nephrotic syndrome remitted with a calcineurin inhibitor medication. CONCLUSION:
      We suggest that the deficiency of STS is another one in an increasing list of
      genetic causes of podocytopathy and nephrotic syndrome. Remission of proteinuria
      in such a case may be achieved with immunosuppressive medication.

PMID- 22419364
TI  - Value of p16(INK4a)  in the diagnosis of low-grade urothelial carcinoma of the
      urinary bladder in urinary cytology.
AB  - BACKGROUND: The sensitivity of urinary cytology for the diagnosis of urothelial
      carcinomas is low, particularly in low-grade carcinomas. The UroVysion test is a
      fluorescent in situ hybridization multiprobe assay that increases the sensitivity
      of urinary cytology. However, this test is not widely available. P16(INK4a) , a
      protein involved in cell cycle progression, is overexpressed in urothelial
      carcinoma. Immunocytochemical expression of p16(INK4a) has been examined in
      biopsy samples from urothelial carcinomas, but few studies have addressed this
      protein in urine cytology. METHODS: The authors compared the results of
      p16(INK4a) immunoreactivity in cytology and biopsy samples from 83 cases,
      including low-grade urothelial carcinomas, reactive epithelial lesions, and
      negative cases. RESULTS: p16(INK4a) assessment of in urine cytology samples
      showed a sensitivity of 66.7% and a specificity of 82.8% in the diagnosis of low
      grade urothelial carcinomas. CONCLUSIONS: On the basis of these results, the
      authors propose that immunocytochemical detection of p16(INK4a) is a reliable
      tool in urine cytology, both for the diagnosis of low-grade urothelial carcinomas
      and for follow-up purposes. More retrospective and prospective studies are
      required to verify these results.

PMID- 22419363
TI  - Associations between cardiorespiratory fitness, physical activity and clustered
      cardiometabolic risk in children and adolescents: the HAPPY study.
AB  - Clustering of cardiometabolic risk factors can occur during childhood and
      predisposes individuals to cardiometabolic disease. This study calculated
      clustered cardiometabolic risk in 100 children and adolescents aged 10-14 years
      (59 girls) and explored differences according to cardiorespiratory fitness (CRF)
      levels and time spent at different physical activity (PA) intensities. CRF was
      determined using a maximal cycle ergometer test, and PA was assessed using
      accelerometry. A cardiometabolic risk score was computed as the sum of the
      standardised scores for waist circumference, blood pressure, total
      cholesterol/high-density lipoprotein ratio, triglycerides and glucose.
      Differences in clustered cardiometabolic risk between fit and unfit participants,
      according to previously proposed health-related threshold values, and between
      tertiles for PA subcomponents were assessed using ANCOVA. Clustered risk was
      significantly lower (p < 0.001) in the fit group (mean 1.21 +/- 3.42) compared to
      the unfit group (mean -0.74 +/- 2.22), while no differences existed between
      tertiles for any subcomponent of PA. Conclusion These findings suggest that CRF
      may have an important cardioprotective role in children and adolescents and
      highlights the importance of promoting CRF in youth.

PMID- 22419365
TI  - Detection algorithm for the validation of human cell lines.
AB  - Cell lines are an important tool in understanding all aspects of cancer growth,
      development, metastasis and tumor cell death. There has been a dramatic increase
      in the number of cell lines and diversity of the cancers they represent; however,
      misidentification and cross-contamination of cell lines can lead to erroneous
      conclusions. One method that has gained favor for authenticating cell lines is
      the use of short tandem repeats (STR) to generate a unique DNA profile. The
      challenge in validating cell lines is the requirement to compare the large number
      of existing STR profiles against cell lines of interest, particularly when
      considering that the profiles of many cell lines have drifted over time and
      original samples are not available. We report here methods that analyze the
      variations and the proportional changes extracted from tetra-nucleotide repeat
      regions in the STR analysis. This technique allows a paired match between a
      target cell line and a reference database of cell lines to find cell lines that
      match within a user designated percentage cut-off quality matrix. Our method
      accounts for DNA instability and can suggest whether the target cell lines are
      misidentified or unstable.

PMID- 22419366
TI  - Ultrastructural analysis of the root canal walls after simultaneous irrigation of
      different sodium hypochlorite concentration and 0.2% chlorhexidine gluconate.
AB  - To determine whether sodium hypochlorite (NaOCl) with 0.2% chlorhexidine
      gluconate (CHX) leads to colour change and precipitate formation, and to
      ultrastructurally analyse the dentine surface after simultaneous irrigation with
      0.5% NaOCl and 0.2% CHX. Four tubes in which 5ml of different NaOCl
      concentrations and 5ml 0,2% CHX were placed, were observed every 15 minutes in
      the first two hours and after 7 days. Mixture solutions were centrifuged at 800
      rpm/4 min. A precipitate is observed under light-microscopy. Thirty-five single
      rooted teeth were instrumented using crown-down technique with irrigation:
      Positive control: distilled water, Negative control: 0,5% NaOCl+15% EDTA,
      Experimental group: identical to the negative control, then canals were treated
      with 0.5% NaOCl+0.2% CHX. The longitudinal root sections were observed under
      scanning-electron-microscopy. The amount of debris was assessed with 5/score
      system, and the results were analysed using the Mann-Whitney U test (p < 0.001).
      Change in colour was noticed immediately after the merger and it did not change
      with time. Mixture solutions showed considerable turbidity, but precipitate was
      observed only after centrifugation. Statistical analysis showed a significant
      difference in the dentinal wall purity when comparing the cervical and middle
      root canal thirds between the experimental and negative control group. The
      difference was also observed between the cervical and middle thirds compared to
      the apical third of the root canal within these groups. Interaction between NaOCl
      and CHX, as well as the creation of precipitates, depends not only on the
      concentration of NaOCl, but also on the concentration of CHX.

PMID- 22419367
TI  - High performance bipolar resistive switching memory devices based on Zn2SnO4
      nanowires.
AB  - The resistive switching behavior of metal-oxide-metal nanoscale devices is a
      fascinating phenomenon of next generation nonvolatile memories. Here, we
      demonstrate nanoscale memristive devices based on Zn(2)SnO(4) nanowires (ZTO NWs)
      for the first time. The devices show high performance bipolar resistive switching
      behaviors, including an ultrafast response speed of 20 ns, a low operation
      voltage of <2 V and long data retention (over 5 months). A physical model of
      metal filament formation along the ZTO NWs has been suggested to explain the
      bipolar resistive switching behavior.

PMID- 22419368
TI  - Relationship of 2D:4D finger ratio with muscle strength, testosterone, and
      androgen receptor CAG repeat genotype.
AB  - This study aimed to examine the relationship between the ratio of the length of
      the second and fourth digits (2D:4D) and locomotor muscle strength. Furthermore,
      two putative mechanisms that might explain any relationship of 2D:4D with muscle
      strength, specifically serum total and free testosterone, and androgen receptor
      genotype CAG repeat number (AR CAGn) were investigated. Seventy-seven healthy
      young Caucasian men completed a thorough assessment of isometric and isokinetic
      knee extensor strength, with unilateral measurements averaged across both legs
      and repeated on two occasions. The lengths of the second and fourth fingers of
      each hand were measured to calculate 2D:4D ratio. Serum total testosterone (TT)
      and serum hormone binding globulin (SHBG) were measured by ELISA and used to
      calculate free testosterone (FT). AR CAGn was determined by PCR and microchip
      electrophoresis. There was no association between mean, left or right hand 2D:4D
      and isometric or isokinetic knee extensor strength (all, R < 0.12, P > 0.32). TT
      and FT were unrelated to mean, left or right hand 2D:4D ratio (all, R < 0.12, P >
      0.34). Finally AR CAGn was not associated with mean, right or left hand 2D:4D
      ratio (all, R < 0.20, P > 0.10). This study found no evidence of 2D:4D being
      related to locomotor muscle strength, TT, FT, or AR CAGn. The reported
      association of 2D:4D with sports performance does not seem to be explained by an
      influence on locomotor muscle strength, and could be due to an effect on motor or
      cognitive skills.

PMID- 22419369
TI  - The rhPTH treatment elevates plasma secreted protein acidic and rich in cysteine
      levels in patients with osteoporosis.
AB  - The secreted protein acidic and rich in cysteine (SPARC), also known as
      osteonectin, plays an important role in osteoblast formation, maturation, and
      survival. Here, we report the effects of recombinant human parathyroid hormone (1
      34) [rhPTH (1-34)], a bone formation-stimulating agent, and elcatonin on plasma
      SPARC levels in patients with osteoporosis. The rhPTH (1-34) treatment
      significantly increased plasma SPARC levels, and the change of plasma SPARC
      correlated positively with changes of lumbar bone mineral density (BMD) at L2-L4.
      These results unveil that SPARC may be a novel marker related to the regulation
      of bone formation. INTRODUCTION: rhPTH (1-34) is known to influence osteoclast
      maturation and activity through modulation of osteoblast-derived cytokines. SPARC
      is the most abundant noncollagenous extracellular matrix protein in the bone. So
      far, however, no study has reported the effects of rhPTH (1-34) administration on
      plasma SPARC levels in patients with osteoporosis. The purpose of this study was
      to compare the response of SPARC and BMD to rhPTH (1-34) and elcatonin in
      postmenopausal women with osteoporosis. METHODS: Women were randomized to either
      once-daily subcutaneous injection of rhPTH (1-34) (20 MUg, N = 89) or once-weekly
      intramuscular injection of elcatonin (200 U, N = 35) for 12 months. Plasma
      biochemical markers of bone turnover and BMD were measured at baseline, 6 and 12
      months after treatment. RESULTS: At baseline, plasma SPARC levels correlated
      positively with lumbar spine BMD in all patients (r = 0.45, p = 0.001). Compared
      with baseline, at 12 months, rhPTH (1-34) significantly increased lumbar spine
      BMD and plasma SPARC levels (p = 0.008 and p = 0.001, respectively), whereas
      elcatonin was ineffective. More importantly, the changes of plasma SPARC
      correlated positively with changes of lumbar BMD at L2-L4 (r = 0.47, p = 0.001)
      in the rhPTH (1-34)-treated group, but not in the elcatonin group. CONCLUSION:
      The increase in plasma SPARC levels during the rhPTH (1-34) treatment may have
      contributed to the anabolic effect on bone formation, and SPARC may be a novel
      marker related to the regulation of bone formation.

PMID- 22419370
TI  - A systematic review of hip fracture incidence and probability of fracture
      worldwide.
AB  - The country-specific risk of hip fracture and the 10-year probability of a major
      osteoporotic fracture were determined on a worldwide basis from a systematic
      review of literature. There was a greater than 10-fold variation in hip fracture
      risk and fracture probability between countries. INTRODUCTION: The present study
      aimed to update the available information base available on the heterogeneity in
      the risk of hip fracture on a worldwide basis. An additional aim was to document
      variations in major fracture probability as determined from the available FRAX
      models. METHODS: Studies on hip fracture risk were identified from 1950 to
      November 2011 by a Medline OVID search. Evaluable studies in each country were
      reviewed for quality and representativeness and a study (studies) chosen to
      represent that country. Age-specific incidence rates were age-standardised to the
      world population in 2010 in men, women and both sexes combined. The 10-year
      probability of a major osteoporotic fracture for a specific clinical scenario was
      computed in those countries for which a FRAX model was available. RESULTS:
      Following quality evaluation, age-standardised rates of hip fracture were
      available for 63 countries and 45 FRAX models available in 40 countries to
      determine fracture probability. There was a greater than 10-fold variation in hip
      fracture risk and fracture probability between countries. CONCLUSIONS: Worldwide,
      there are marked variations in hip fracture rates and in the 10-year probability
      of major osteoporotic fractures. The variation is sufficiently large that these
      cannot be explained by the often multiple sources of error in the ascertainment
      of cases or the catchment population. Understanding the reasons for this
      heterogeneity may lead to global strategies for the prevention of fractures.

PMID- 22419371
TI  - Hodgkin's lymphoma RNA-transfected dendritic cells induce cancer/testis antigen
      specific immune responses.
AB  - Cytotoxic T lymphocytes (CTL) can kill Hodgkin's lymphoma (HL) cells, and CTL
      have been used for the treatment of Epstein-Barr virus (EBV)-positive HL. For
      patients with EBV-negative HL, this strategy cannot be employed and alternative
      target structures have to be defined. In order to establish a system for the
      stimulation of HL-reactive T cells, we used dendritic cells (DC) as antigen
      presenting cells for autologous T cells and transfected these DC with RNA from
      established HL cell lines. After stimulation of peripheral blood mononuclear
      cells (PBMC) with RNA-transfected DC, we analyzed the reactivity of primed PBMC
      by interferon gamma enzyme-linked immunospot. Our results suggest the presence of
      antigens with expression in HL cell lines and recognition of these antigens in
      combination with DC-derived human leukocyte antigen molecules. By the analysis of
      Gene Expression Omnibus microarray data sets from HL cell lines and primary HL
      samples in comparison with testis and other normal tissues, we identified HL
      associated cancer testis antigens (CTA) including the preferentially expressed
      antigen in melanoma (PRAME). After stimulation of PBMC with RNA-transfected DC,
      we detected PRAME-reactive T cells. PRAME and other HL-associated CTA might be
      targets for HL-specific immune therapy or for the monitoring of HL-directed
      immune responses.

PMID- 22419372
TI  - Macrophage polarization induced by neuropeptide methionine enkephalin (MENK)
      promotes tumoricidal responses.
AB  - The aim of this study is to investigate macrophages polarization induced by
      methionine enkephalin (MENK) that promotes tumoricidal responses in vivo and in
      vitro. Both phenotypic and functional activities of macrophages were assessed by
      the quantitative analysis of key surface molecules on macrophages with flow
      cytometry, immunofluorescent staining, and the production of cytokines with
      enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain
      reaction. Our results showed that MENK could down-regulate the expression of
      CD206 and the production of arginase-1 (the markers of alternatively activated
      (M2) macrophage) in tumor-associated macrophages in vivo, meanwhile it could
      significantly up-regulate the expression of CD64, MHC-II, and the production of
      induced nitric oxide synthase (the markers of classically activated (M1)
      macrophages). Furthermore, the studies on bone marrow-derived macrophages treated
      with MENK (10(-12) M) in vitro had demonstrated that MENK could markedly increase
      tumoricidal activity. MENK could also enhance the release of reactive oxidant
      species and the production of interleukin-12p40, tumor necrosis factor-alpha,
      while decrease the production of interleukin-10. In conclusion, MENK could
      effectively induce M2 macrophages polarizing to M1 macrophages, sequentially to
      modulate the Th1 responses of the host immune system. Our results suggest that
      MENK might have great potential as a new therapeutic agent for cancer.

PMID- 22419373
TI  - Detecting symmetry and faces: separating the tasks and identifying their
      interactions.
AB  - Face and symmetry processing have common characteristics, and several lines of
      evidence suggest they interact. To characterize their relationship and possible
      interactions, in the present study we created a novel library of images in which
      symmetry and face-likeness were manipulated independently. Participants
      identified the target that was most symmetric among distractors of equal face
      likeness (Experiment 1) and identified the target that was most face-like among
      distractors of equal symmetry (Experiment 2). In Experiment 1, we found that
      symmetry judgments improved when the stimuli were more face-like. In Experiment
      2, we found a more complex interaction: Image symmetry had no effect on detecting
      frontally viewed faces, but worsened performance for nonfrontally viewed faces.
      There was no difference in performance for upright versus inverted images,
      suggesting that these interactions occurred on the parts-based level. In sum,
      when symmetry and face-likeness are independently manipulated, we find that each
      influences the perception of the other, but the nature of the interactions
      differs.

PMID- 22419374
TI  - Laboratory and field methods for measuring human energy expenditure.
AB  - Energetics research is central to the field of human biology. Energy is an
      important currency for measuring adaptation, because both its acquisition and
      allocation for biological processes have important implications for survival and
      reproduction. Recent technological and methodological advances are now allowing
      human biologists to study variation in energy dynamics with much greater accuracy
      in a wide variety of ecological contexts. This article provides an overview of
      the methods used for measuring human energy expenditure (EE) and considers some
      of the important ecological and evolutionary questions that can be explored from
      an energetics perspective. Basic principles of calorimetry are first presented,
      followed by an overview of the equipment used for measuring human EE and work
      capacity. Methods for measuring three important dimensions of human EE-resting
      metabolic rate, working/exercising EE, and total EE-are then presented,
      highlighting key areas of ongoing research.

PMID- 22419375
TI  - Chronic kidney disease and the risk of stent thrombosis after percutaneous
      coronary intervention with drug-eluting stents.
AB  - BACKGROUND: Chronic kidney disease (CKD) has been demonstrated to be associated
      with adverse clinical outcomes for patients with coronary artery disease (CAD).
      However, data on relation of CKD and stent thrombosis (ST) after drug-eluting
      stent (DES) implantation are limited. OBJECTIVES: This study was designed to
      examine whether CKD is associated with higher incidence of ST after elective
      coronary DES implantation compared with patients with normal renal function.
      METHODS: We consecutively enrolled 2,862 patients undergoing elective
      percutaneous coronary intervention (PCI) with DES. Demographic and clinical data
      were collected preoperatively. CKD was defined as estimated glomerular filtration
      rate (eGFR) < 60 ml/min, calculated using the modified MDRD equation. The primary
      outcome was 1-year definite or probable ST. RESULTS: Four hundred and forty-five
      participants (15.5%) had CKD before procedure. The incidence of 1-year definite
      or probable ST was significantly higher in CKD patients compared with patients
      with normal renal function (1.8% vs. 0.6%, P = 0.014). After adjustment for
      multiple clinical and biochemical covariates, CKD was an independent predictor of
      1-year definite or probable ST (hazard rate [HR] 0.396, 95% CI 0.165-0.951, P =
      0.038). CONCLUSION: CKD is significantly associated with increased incidence of 1
      year definite or probable ST in patients undergoing PCI with DES.

PMID- 22419376
TI  - Mercury exposure assessment in Iranian pregnant women's hair with respect to
      diet, amalgam filling, and lactation.
AB  - Our aim for carrying out this study was to estimate the levels of mercury in the
      hair of pregnant women and its association with fish consumption and amalgam
      fillings. From November 2007 to January 2008, 100 hair samples were collected
      randomly from three groups of pregnant women: Ahvaz in the south of Iran,
      Noushahr in the north, and the countryside of Noushahr. Significant differences
      were found in these three groups of pregnant women's samples (p>0.05). The mean
      mercury level in women's hair was found to be 0.37 MUg/g (range, 0.11-3.57
      MUg/g). Only in 2 % of collected hair samples did the total mercury (THg) level
      exceed the United States Environmental Protection Agency-recommended 1.0 MUg/g.
      In addition, there was a positive correlation of THg content in Ahvaz group's
      samples with respect to fish consumption (r=0.41, p=0.02) and a negative
      correlation of THg content in those who consumed vegetables and fruit. The level
      of education also played an indicating factor in this group. Moreover,
      significant association was found between the residence time and Hg concentration
      of women's hair samples collected from Noushahr (p>0.05). Similarly, the same
      correlations were found between hair mercury levels and the time since the first
      filling, number of dental fillings, pregnancy interval, and lactating period.

PMID- 22419377
TI  - Effect of dietary Garcinia cambogia extract on serum essential minerals (calcium,
      phosphorus, magnesium) and trace elements (iron, copper, zinc) in rats fed with
      high-lipid diet.
AB  - The aim of the study was to investigate the effect of Garcinia cambogia extract
      on serum calcium (Ca), phosphorus (P), magnesium (Mg), iron (Fe), zinc (Zn) and
      copper (Cu) concentrations in rats fed with the normal or the high-lipid and 
      cholesterol diet. Thirty 1-year-old female Sprague-Dawley rats (pathogen-free),
      weighing an average of 229 g, were randomly assigned to three experimental groups
      of ten animals each. Diets and tap water were given ad libitum for 75 days. Group
      1 (control group) was fed with basal diet (2 % liquid vegetable oil, 0 %
      cholesterol), while the diets of groups 2 and 3 contained vegetable oil (2 %
      liquid vegetable oil and 5 % hydrogenated vegetable oil) and cholesterol (3 %) in
      high levels. 4,5 % G. cambogia extract containing 65 % HCA was added to the diet
      of group 3 as from day 45. Blood samples were withdrawn on days 0, 45 and 75.
      Serum mineral levels were analyzed using standard enzymatic colorimetric methods
      with a spectrophotometer. All significant differences were p<0.05. Serum Ca
      levels were not significantly different between all groups on days 45 and 75.
      Serum P level was significantly higher in the group fed with high-lipid diet and
      G. cambogia extract than in the control group on day 45. Serum Mg level was
      significantly higher in group 2 than in the control group on day 45. Serum Fe
      levels were significantly lower in the control group than in the other groups on
      days 45 and 75. Serum Zn level of the group fed with high-lipid diet and G.
      cambogia extract was significantly higher than in the control group on day 75.
      Serum Cu levels were significantly higher in group 2 than in the control group,
      and in group 3 than in group 2 on day 75. In conclusion, a diet containing the
      high fat amounts may lead to the increase in circular levels of some minerals due
      to the short-chain fatty acid production lowering the luminal pH which increases
      mineral solubility, or serving as a fuel for mucosal cells and stimulating cell
      proliferation in the large intestine. G. cambogia extract may be used in the P
      and Cu deficiencies due to increases resulting in the present P and Cu amounts in
      G. cambogia extract, or the use of phytate P in diet. It was hoped that with
      further evidence-based study this product will enter to mainstream medicines.

PMID- 22419378
TI  - 'Fagiolo a Formella', an Italian lima bean ecotype: biochemical and nutritional
      characterisation of dry and processed seeds.
AB  - BACKGROUND: An ecotype of the lima bean, named 'fagiolo a Formella', which, to
      the best of our knowledge, is the only example of an Italian lima bean (Phaseolus
      lunatus L.) ecotype, is cultivated in the Campania region of southern Italy.
      Physical, nutritional and processing traits of dry seeds were evaluated for two
      consecutive growing seasons (2009 and 2010). The canning quality was also
      investigated, but only for the harvest of 2010. RESULTS: Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of total seed proteins allowed the attribution
      of 'fagiolo a Formella' to the Mesoamerican gene pool and Sieva morphotype. Seeds
      have a trapezoid shape, white coat and 100-seed weight greater than 42 g. Yield,
      protein, trypsin inhibitor and phytic acid values were found comparable with
      those reported for lima bean varieties cultivated in sub-tropical areas.
      Moreover, we found that this ecotype is devoid of lectin. CONCLUSIONS: The good
      adaptation to growing environment is indicated by the fact that 'fagiolo a
      Formella' seed quality is comparable to that of lima beans grown in America.
      Overall the canning quality was found satisfactory and canning significantly
      destroys the main anti-nutritional compounds present in dry seeds.

PMID- 22419379
TI  - O2 insertion into a cadmium-carbon bond: structural characterization of
      organocadmium peroxides.

PMID- 22419380
TI  - Brief report: assessment of the social-emotional profile in children with autism
      spectrum disorders using a novel comic strip task.
AB  - This study investigated whether the novel Comic Strip Task (CST) could be used to
      detect Theory-of-Mind impairments (ToM) in 4- to 8-year-old children with high
      functioning Autism Spectrum Disorders (ASD). Twelve children with either high
      functioning autism or Asperger's Disorder and 12 typically-developing children
      completed the 21-item measure. The overall CST demonstrated moderate internal
      consistency but the Belief-understanding subscale was excluded from the test due
      to poor reliability. As predicted, the ASD group performed significantly more
      poorly than controls on the overall 2-subscale CST and on the intention
      understanding subscale. No group differences were found in emotion-understanding
      subscale performance. Controlling for age, verbal ability was positively
      correlated with overall CST performance across groups. CST performance in the ASD
      group positively correlated with parent-reports of communication difficulties.
      Despite some limitations with the belief-understanding subscale, the CST has
      promising psychometric features warranting further development of this measure.

PMID- 22419381
TI  - A novel maternally-derived insertional translocation resulting in partial trisomy
      4q13.2-q22.1 with complex translocation t(8;20) in a family with intellectual
      disability.
AB  - We characterized the chromosomal aberration in family with intellectual
      disability, including two affected children and their affected mother. Initial
      standard karyotypes of the three individuals showed an apparently balanced
      translocation of chromosomes 8 and 20. Using molecular cytogenetic techniques, we
      observed complex structural chromosomal aberration comprising of reciprocal
      translocation between chromosomes 8 and 20 with pericentric inversion
      (8p11.12q22.3) and insertion of chromosome 4 segments into both der(8) and
      der(20). In particular, the insertion of chromosome 4 was complex. Two segments
      (4q13.2-q13.3 and 4q21.21-q22.1) were inserted into the der(8)t(8;20) breakpoint
      and one segment (4q13.3-q21.21) into the der(20)t(8;20) breakpoint. Both children
      inherited two normal chromosomes 4 from their parents and the der(8) and der(20)
      from the mother, resulting in partial trisomy of 4q13.2-q22.1. Interestingly, the
      mother, in addition to the same complex insertions and inversion, was founded to
      have a deletion of 4q13.2-q22.1 in one of her chromosomes 4, yielding no genetic
      imbalance but with potential disruption of intellectual dysfunction-related
      gene(s) at the breakpoints as the cause of her intellectual impairment. This
      family is the third case report of an insertional translocation mechanism causing
      partial trisomy 4q syndrome. Our study demonstrates that an insertion of an extra
      chromosomal segment, not primarily involving in translocation breakpoints, which
      results in partial trisomy, can be an unapparent cause of the abnormal
      phenotypes.

PMID- 22419382
TI  - Can we prevent incontinence? ICI-RS 2011.
AB  - AIMS: A review of the current state of research with regard to prevention of
      incontinence. METHODS: The search was limited to English language publications on
      the topic of incontinence prevention. RESULTS: Incontinence is associated with a
      range of risk factors, most of which are modifiable. Lifestyle changes with
      behavioral modifications that can prevent urinary incontinence (UI) need to be
      adopted from an early phase of life. Pregnancy per se for the woman, independent
      of labor and delivery practice, is a risk factor for UI. The influence of
      estrogen is still under discussion as to its direct influence to UI. For both men
      and women, there is a correlation between pelvic-floor related surgery and UI and
      fecal incontinence (FI). With further improvement in surgical techniques, UI is
      often only a transient symptom for most patients. Psychological illnesses and
      their treatment can induce or worsen incontinence and therefore should be
      evaluated especially with other necessary co-medications. CONCLUSIONS: The
      evidence would suggest that in some cases incontinence can be prevented. Although
      the evidence base for UI is greater than that for FI, the conditions share many
      similarities with respect to risk and treatment, suggesting that similar benefits
      may derive from population-based prevention strategies. With primary prevention,
      actions taken early, even in the absence of incontinence, may avoid or delay its
      onset. There is also evidence that some risk factors for incontinence are
      modifiable, although not type specific, and can be reduced through preventive
      measures.

PMID- 22419383
TI  - Hydrothermal treatment of grass: a low-cost, green route to nitrogen-doped,
      carbon-rich, photoluminescent polymer nanodots as an effective fluorescent
      sensing platform for label-free detection of Cu(II) ions.
AB  - Increasing reaction temperature produces photoluminescent polymer nanodots
      (PPNDs) with decreased particle size and increased quantum yield. Such PPNDs are
      used as an effective fluorescent sensing platform for label-free sensitive and
      selective detection of Cu(II) ions with a detection limit as low as 1 nM. This
      method is successfully applied to determine Cu(2+)  in real water samples.

PMID- 22419384
TI  - Photoimmune protective effect of the phytoestrogenic isoflavonoid equol is
      partially due to its antioxidant activities.
AB  - Topical application of lotions containing the phytoestrogenic isoflavonoid equol
      have been reported to protect mice against UV radiation-induced inflammation,
      immune suppression and photocarcinogenesis. The photoimmune protective property
      was shown to depend on equol's activation of oestrogen receptor signalling in the
      skin. However, isoflavones are also recognised for their antioxidant properties
      in biological systems. As endogenous cutaneous antioxidant enzymes including the
      inducible stress protein haem oxygenase (HO)-1, have photoprotective efficacy,
      this study in the Skh:hr-1 hairless mouse seeks evidence for an antioxidant role
      for equol in contributing to its photoimmune protection. Oxidative stress has
      been measured as UVA-induced lipid peroxidation in the mouse skin, and was dose
      dependently inhibited by topical equol. Inhibition of the UVA (320-400 nm)
      inducible HO activity significantly reduced the level of equol protection against
      lipid peroxidation, thereby attributing a component of equol's lipid protection
      capacity to this stress enzyme. It was consistent that topical equol enhanced the
      level of HO induction by UVA irradiation in both skin and liver. Subsequently,
      the dose-dependent protection by topical equol lotions against solar simulated UV
      radiation induced immunosuppression, measured by the contact hypersensitivity
      reaction, was found also to be partially reduced by the inhibition of HO
      activity. Therefore, in addition to the activation by equol of oestrogenic
      signalling pathways for photoprotection, this isoflavonoid also provides UV
      protective antioxidant effects that depend partially on HO-1 induction.

PMID- 22419385
TI  - The causal mediation formula--a guide to the assessment of pathways and
      mechanisms.
AB  - Recent advances in causal inference have given rise to a general and easy-to-use
      formula for assessing the extent to which the effect of one variable on another
      is mediated by a third. This Mediation Formula is applicable to nonlinear models
      with both discrete and continuous variables, and permits the evaluation of path
      specific effects with minimal assumptions regarding the data-generating process.
      We demonstrate the use of the Mediation Formula in simple examples and illustrate
      why parametric methods of analysis yield distorted results, even when parameters
      are known precisely. We stress the importance of distinguishing between the
      necessary and sufficient interpretations of "mediated-effect" and show how to
      estimate the two components in nonlinear systems with continuous and categorical
      variables.

PMID- 22419386
TI  - Structured histopathology profiling of chronic rhinosinusitis in routine
      practice.
AB  - BACKGROUND: Tissue eosinophilia in chronic rhinosinusitis (CRS) is a marker of
      inflammatory disorders recalcitrant to surgical intervention. Eosinophilic
      chronic rhinosinusitis (ECRS) is traditionally associated with asthma, polyps,
      aspirin sensitivity, high serum eosinophilia, and elevated immunoglobulin E
      (IgE). However, patients with ECRS may not present with these associations and
      there is a need to establish other surrogate markers. The objective of the study
      was to determine the associations between the histopathology, serology, and
      clinical characteristics in CRS patients. METHODS: A cross-sectional study was
      undertaken of CRS patients undergoing surgery. Tissue eosinophilia and other
      pathological features were compared to traditional surrogate features of ECRS, as
      well as to symptoms, and to radiologic and endoscopic scores. RESULTS: A total of
      51 patients were assessed (47% female, mean age 46.6 +/- 4.1 years). High tissue
      eosinophilia (>10 per high-power field [HPF]) was more prominent in polyps (84%)
      (chi(2) = 25.76; p < 0.01) but was also seen in nonpolyp patients (19%). Asthma
      was not associated with high tissue eosinophilia (p = 0.60), with 43% of
      nonasthmatics demonstrating high tissue eosinophilia. Serum eosinophilia
      predicted high tissue eosinophilia at >0.30 * 10(9)/L or 4.4% of leukocytes
      (sensitivity 52%, specificity 87%, receiver operating characteristic [ROC] p =
      0.001), with low negative predictive value. Serum IgE was nonpredictive (p =
      0.08). CONCLUSION: The diagnosis of ECRS has unique prognostic implications.
      Traditional features of the ECRS phenotype are not necessarily reliable markers
      for the presence of tissue eosinophilia. Serum eosinophilia may be a good
      surrogate marker of tissue eosinophilia but of limited use. The routine use of
      structured histopathology reporting in CRS is suggested, to allow for the
      diagnosis of ECRS and to identify other prognostic markers.

PMID- 22419387
TI  - Natural occurrence of aflatoxin B1 in sorghum grown in different geographical
      regions of India.
AB  - BACKGROUND: Sorghum (Sorghum bicolor (L.) Moench) is an important coarse cereal
      crop grown for grain and fodder in the semi-arid Tropics, mainly in Asian and
      African countries. In India sorghum is consumed as human food and poultry feed.
      Sorghum grain grown in the rainy season (kharif) is becoming severely affected by
      grain moulds, the major fungi involved being Aspergillus, Fusarium and
      Curvularia. If the extent of mould is severe, the grain is unsafe for consumption
      owing to contamination by mycotoxins. RESULTS: This paper presents a multi-centre
      study conducted in sorghum to evaluate natural contamination of aflatoxin B(1) in
      India. A total of 1606 grain sorghum samples were collected during the rainy
      (kharif) season across 4 years from seven states of India, representing different
      geographical regions of the country. Aflatoxin B(1) contamination during 2007-08
      was the highest (13.1%), followed by samples from the year 2004-05 (2.85%). The
      samples collected in years 2005-06 and 2006-07 showed contamination below 1%. The
      number of samples (35) showing aflatoxin B(1) contamination above the safety
      limit was also highest during 2007-08 as compared to samples from the other
      years. CONCLUSION: This study, conducted for 4 years, showed that natural
      contamination of aflatoxin B(1) in sorghum grown in India is within safety limits
      (20 ug kg(-1)) recommended by the Codex Alimentarius Committee and 73% of samples
      were positive for toxin. However, 0.75% (12) of total samples contained aflatoxin
      above the safety limit. The overall occurrence of toxin from Madhya Pradesh and
      Rajasthan was below 5 ug kg(-1).

PMID- 22419389
TI  - Dynamic electrostatic lithography: multiscale on-demand patterning on large-area
      curved surfaces.
AB  - Dynamic electrostatic lithography is invented to dynamically generate various
      patterns on large-area and curved polymer surfaces under the control of
      electrical voltages. The shape of the pattern can be tuned from random creases
      and craters to aligned creases, craters and lines, and the size of the pattern
      from millimeters to sub-micrometers.

PMID- 22419388
TI  - Induction of proapoptotic antibodies to triple-negative breast cancer by
      vaccination with TRAIL death receptor DR5 DNA.
AB  - TNF-related apoptosis-inducing ligand receptor 2 [TRAIL-R2 or death receptor 5
      (DR5)] is expressed at elevated levels in a broad range of solid tumors to
      mediate apoptotic signals from TRAIL or agonist antibodies. We tested the
      hypothesis that DR5 DNA vaccination will induce proapoptotic antibody to trigger
      apoptosis of tumor cells. BALB/c mice were electrovaccinated with DNA-encoding
      wild-type human DR5 (phDR5) or its derivatives. Resulting immune serum or
      purified immune IgG induced apoptosis in triple-negative breast cancer (TNBC)
      cells, which were also TRAIL sensitive. The proapoptotic activity of immune serum
      at dilutions of 0.5-2% was comparable to that of 1-2 MUg/ml of TRAIL. Apoptotic
      activity of immune serum was enhanced by antibody crosslinking. Apoptotic cell
      death induced by anti-DR5 antibody was shown by the cleavage of PARP and caspase
      3. In contrast, immune serum had no effect on the proliferation of activated
      human T cells, which expressed low levels of DR5. In vivo, hDR5 reactive immune
      serum prevented growth of SUM159 TNBC cells in severe combined immune-deficient
      mice. DR5-specific IFN-gamma-secreting T cells were also induced by DNA
      vaccination. Furthermore, the feasibility to overcome immune tolerance to self
      DR5 was shown by the induction of mouse DR5-binding antibody after
      electrovaccination of BALB/c mice with pmDR5ectm-Td1 encoding a fusion protein of
      mouse DR5 and an immunogenic fragment of tetanus toxin. These findings support
      DR5 as a promising vaccine target for controlling TNBC and other DR5-positive
      cancers.

PMID- 22419390
TI  - Basic reproduction ratio for a fishery model in a patchy environment.
AB  - We present a dynamical model of a multi-site fishery. The fish stock is located
      on a discrete set of fish habitats where it is catched by the fishing fleet. We
      assume that fishes remain on fishing habitats while the fishing vessels can move
      at a fast time scale to visit the different fishing sites. We use the existence
      of two time scales to reduce the dimension of the model : we build an aggregated
      model considering the habitat fish densities and the total fishing effort. We
      explore a regulation procedure, which imposes an average residence time in
      patches. Several equilibria exist, a Fishery Free Equilibria (FFEs) as well as a
      Sustainable Fishery Equilibria (SFEs). We show that the dynamics depends on a
      threshold which is similar to a basic reproduction ratio for the fishery. When
      the basic reproduction ratio is less or equal to 1, one of the FFEs is globally
      asymptotically stable (GAS), otherwise one of the SFEs is GAS.

PMID- 22419392
TI  - Predictive value and reward in implicit classification learning.
AB  - Learning efficacy depends on its emotional context. The contents learned and the
      feedback received during training tinges this context. The objective here was to
      investigate the influence of content and feedback on the efficacy of implicit
      learning and to explore using functional imaging how these factors are processed
      in the brain. Twenty-one participants completed 150 trials of a probabilistic
      classification task (predicting sun or rain based on combinations of playing
      cards). Smileys or frowneys were presented as feedback. In 10 of these subjects,
      the task was performed during functional magnetic resonance imaging. Card
      combinations predicting sun were remembered better than those predicting rain.
      Similarly, positive feedback fortified learning more than negative feedback. The
      presentation of smileys recruited bilateral nucleus accumbens, sensorimotor
      cortex, and posterior cingulum more than negative feedback did. The higher the
      predictive value of a card combination, the more activation was found in the
      lateral cerebellum. Both context and feedback influence implicit classification
      learning. Similar to motor skill acquisition, positive feedback during
      classification learning is processed in part within the sensorimotor cortex,
      potentially reflecting the activation of a dopaminergic projection to motor
      cortex (Hosp et al., 2011). Activation of the lateral cerebellum during learning
      of combinations with high predictive value may reflect the formation of an
      internal model.

PMID- 22419391
TI  - Early-onset osteoarthritis in Ehlers-Danlos syndrome type VIII.

PMID- 22419393
TI  - Immune tolerance: are regulatory T cell subsets needed to explain suppression of
      autoimmunity?
AB  - The potential for self-reactive T cells to cause autoimmune disease is held in
      check by Foxp3(+)  regulatory T cells (Tregs), essential mediators of peripheral
      immunological tolerance. Tregs have the capacity to suppress multiple branches of
      the immune system, tightly controlling the different subsets of effector T cells
      across multiple different tissue environments. Recent genetic experiments have
      found mutations that disrupt specific Treg: effector T cell relationships,
      leading to the possibility that subsets of Tregs are required to suppress each
      subset of effector T cells. Here we review the environmental factors and
      mechanisms that allow Tregs to suppress specific subsets of effector T cells, and
      find that a parsimonious explanation of the genetic data can be made without
      invoking Treg subsets. Instead, Tregs show a functional and chemotactic
      plasticity based on microenvironmental influences that allows the common pool of
      cells to suppress multiple distinct immune responses.

PMID- 22419394
TI  - Transition analysis: a validation study with known-age modern American skeletons.
AB  - Transition Analysis-a recent skeletal age-estimation procedure (Boldsen et al.:
      Paleodemography: age distributions from skeletal samples (2002) 73-106)-is
      evaluated using 252 known-age modern American males and females from the Bass
      Donated Collection and Mercyhurst forensic cases. The pubic symphysis worked best
      for estimating age, followed by the sacroiliac joint and cranial sutures.
      Estimates based on all skeletal characteristics are influenced by the choice of
      prior distribution, although its effect is dwarfed by both the inaccuracy and
      imprecision of age estimates. Age intervals are narrowest for young adults, but
      are surprisingly short in old age as well. When using an informative prior
      distribution, the greatest uncertainty occurs from the late 40s into the 70s.
      Transition Analysis estimates do not perform as well as experience-based
      assessments, indicating the existing procedure is too narrowly focused on
      commonly used pelvic and cranial structures.

PMID- 22419396
TI  - Climate zone delineation: evaluating approaches for use in natural resource
      management.
AB  - Recent efforts by the United States Department of the Interior (DOI) have the
      potential to make climate zones the basic geographic units guiding monitoring and
      resource management programs in the western U.S. We evaluated a new National Park
      Service approach for delineating climate zones that will likely be a model for
      other DOI agencies. Using the test case of the Greater Yellowstone Area in
      Wyoming, Montana and Idaho, we conducted three separate analyses, each based on a
      different dataset. Cluster analysis of 1971-2000 temperature and precipitation
      normals grouped weather stations according to similarities in seasonal patterns.
      Principal Components Analysis (PCAs) of 1895-2008 monthly data grouped stations
      by similarities in long-term variability. Finally, an analysis of snow data
      further subdivided the zones defined by the other two analyses. The climate zones
      produced by the cluster analysis and the PCAs were roughly similar to each other,
      but the differences were significant. The two sets of zones may be useful for
      different applications. For example, studies that analyze links between climate
      patterns and the demography of threatened species should focus on the results of
      the PCAs. The broad similarity among results produced by the different approaches
      supported the application of these zones in climate-related monitoring and
      analysis. However, since choices in data and methodology can affect the details
      of maps depicting zone boundaries, there are practical limitations to their use.

PMID- 22419397
TI  - Assessing riparian conservation land management practice impacts on gully erosion
      in Iowa.
AB  - Well-established perennial vegetation in riparian areas of agricultural lands can
      stabilize the end points of gullies and reduce their overall erosion. The
      objective of this study was to investigate the impacts of riparian land
      management on gully erosion. A field survey documented the number of gullies and
      cattle access points in riparian forest buffers, grass filters, annual row
      cropped fields, pastures in which the cattle were fenced out of the stream, and
      continuously, rotationally and intensive rotationally grazed pastures in three
      regions of Iowa. Gully lengths, depths and severely eroding bank areas were
      measured. Gullies exhibited few significant differences among riparian management
      practices. The most significant differences were exhibited between conservation
      and agricultural management practices, an indication that conservation practices
      could reduce gully erosion. Changes in pasture management from continuous to
      rotational or intensive rotational grazing showed no reductions in gully erosion.
      It is important to recognize that more significant differences among riparian
      management practices were not exhibited because the conservation and alternative
      grazing practices had recently been established. As gully formation is more
      impacted by upland than riparian management, gully stabilization might require
      additional upland conservation practices. The existence of numerous cattle access
      points in pastures where cattle have full access to the stream also indicates
      that these could be substantial sources of sediment for streams. Finally, the
      gully banks were less important sediment contributors to streams than the
      streambanks. The severely eroding bank areas in streams were six times greater
      than those in the gullies in the monitored reaches.

PMID- 22419398
TI  - The impact of land use/land cover changes on land degradation dynamics: a
      Mediterranean case study.
AB  - In the last decades, due to climate changes, soil deterioration, and Land
      Use/Land Cover Changes (LULCCs), land degradation risk has become one of the most
      important ecological issues at the global level. Land degradation involves two
      interlocking systems: the natural ecosystem and the socio-economic system. The
      complexity of land degradation processes should be addressed using a
      multidisciplinary approach. Therefore, the aim of this work is to assess
      diachronically land degradation dynamics under changing land covers. This paper
      analyzes LULCCs and the parallel increase in the level of land sensitivity to
      degradation along the coastal belt of Sardinia (Italy), a typical Mediterranean
      region where human pressure affects the landscape characteristics through fires,
      intensive agricultural practices, land abandonment, urban sprawl, and tourism
      concentration. Results reveal that two factors mainly affect the level of land
      sensitivity to degradation in the study area: (i) land abandonment and (ii)
      unsustainable use of rural and peri-urban areas. Taken together, these factors
      represent the primary cause of the LULCCs observed in coastal Sardinia. By
      linking the structural features of the Mediterranean landscape with its
      functional land degradation dynamics over time, these results contribute to
      orienting policies for sustainable land management in Mediterranean coastal
      areas.

PMID- 22419399
TI  - Navigating the perfect storm: research strategies for socialecological systems in
      a rapidly evolving world.
AB  - The 'Perfect Storm' metaphor describes a combination of events that causes a
      surprising or dramatic impact. It lends an evolutionary perspective to how social
      ecological interactions change. Thus, we argue that an improved understanding of
      how social-ecological systems have evolved up to the present is necessary for the
      modelling, understanding and anticipation of current and future social-ecological
      systems. Here we consider the implications of an evolutionary perspective for
      designing research approaches. One desirable approach is the creation of multi
      decadal records produced by integrating palaeoenvironmental, instrument and
      documentary sources at multiple spatial scales. We also consider the potential
      for improved analytical and modelling approaches by developing system dynamical,
      cellular and agent-based models, observing complex behaviour in social-ecological
      systems against which to test systems dynamical theory, and drawing better
      lessons from history. Alongside these is the need to find more appropriate ways
      to communicate complex systems, risk and uncertainty to the public and to policy
      makers.

PMID- 22419400
TI  - Morphogenesis of the human laryngeal ventricles.
AB  - BACKGROUND: Two theories explain the origin of human laryngeal ventricles: (1)
      ventricles derive from the fifth pharyngeal pouches; (2) development independent
      from the pouches. METHODS: In all, there were 21 serially sectioned human embryos
      from stages 15 to 23, and 11 fetuses of 9 to 18 weeks. Computer-aided 3
      dimentional reconstructions were made. RESULTS: The cranial part of the laryngeal
      sulcus and future vestibule expands from the pharyngeal floor between the third
      and fourth pharyngeal pouches during stages 15 and 16 (33-37 days). The primordia
      of the ventricles appeared at stage 18 (44 days) as 2 lateral swellings in the
      caudal end of the future vestibule, limited by the third pharyngeal pouches.
      Active epithelial expansion and subsequent canalization during late embryonic and
      early fetal periods finalizes their development. CONCLUSIONS: The laryngeal
      ventricles do not derive from the pharyngeal pouches but the median region of the
      pharyngeal floor between the third and fourth pharyngeal pouches and arches at
      the caudal end of the future vestibule.

PMID- 22419401
TI  - Low-intensity pulsed ultrasound accelerates fracture healing by stimulation of
      recruitment of both local and circulating osteogenic progenitors.
AB  - We investigated the effect of low-intensity pulsed ultrasound (LIPUS) on the
      homing of circulating osteogenic progenitors to the fracture site. Parabiotic
      animals were formed by surgically conjoining a green fluorescent protein (GFP)
      mouse and a syngeneic wild-type mouse. A transverse femoral fracture was made in
      the contralateral hind limb of the wild-type partner. The fracture site was
      exposed to daily LIPUS in the treatment group. Animals without LIPUS treatment
      served as the control group. Radiological assessment showed that the hard callus
      area was significantly greater in the LIPUS group than in the control group at 2
      and 4 weeks post-fracture. Histomorphometric analysis at the fracture site showed
      a significant increase of GFP cells in the LIPUS group after 2 weeks (7.5%),
      compared to the control group (2.4%) (p < 0.05). The LIPUS group exhibited a
      significantly higher percentage of GFP cells expressing alkaline phosphatase
      (GFP/AP) than the control group at 2 weeks post-fracture (5.9%, 0.3%,
      respectively, p < 0.05). There was no significant difference in the percentage of
      GFP/AP cells between the LIPUS group (2.0%) and the control group (1.4%) at 4
      weeks post-fracture. Stromal cell derived factor-1 and CXCR4 were
      immunohistochemically identified at the fracture site in the LIPUS group. These
      data indicate that LIPUS induced the homing of circulating osteogenic progenitors
      to the fracture site for possible contribution to new bone formation.

PMID- 22419402
TI  - Coil embolization of left coronary artery pseudoaneurysms arising as a
      complication of percutaneous coronary intervention.
AB  - Coronary aneurysms and pseudoaneurysms have been described as rare complications
      following percutaneous coronary intervention (PCI). There is limited data
      available on the optimal treatment strategy for these conditions. Use of
      noninvasive techniques including covered stents has been described as a potential
      therapeutic strategy. We report a case of percutaneous coil embolization of two
      enlarging left anterior descending pseudoaneurysms arising as a complication of
      PCI.

PMID- 22419403
TI  - Audience design affects acoustic reduction via production facilitation.
AB  - In this article, we examine the hypothesis that acoustic variation (e.g., reduced
      vs. prominent forms) results from audience design. Bard et al. (Journal of Memory
      and Language 42:1-22, 2000) have argued that acoustic prominence is unaffected by
      the speaker's estimate of addressee knowledge, using paradigms that contrast
      speaker and addressee knowledge. This question was tested in a novel paradigm,
      focusing on the effects of addressees' feedback about their understanding of the
      speaker's intended message. Speakers gave instructions to addressees about where
      to place objects (e.g., the teapot goes on red). The addressee either anticipated
      the object, by picking it up before the instruction, or waited for the
      instruction. For anticipating addressees, speakers began speaking more quickly
      and pronounced the word the with shorter duration, demonstrating effects of
      audience design. However, no effects appeared on the head noun (e.g., teapot), as
      measured by duration, amplitude, and perceived intelligibility. These results are
      consistent with a mechanism in which evidence about addressee understanding
      facilitates production processes, as opposed to triggering particular acoustic
      forms.

PMID- 22419404
TI  - Reaching for words and nonwords: interactive effects of word frequency and
      stimulus quality on the characteristics of reaching movements.
AB  - Word frequency and stimulus degradation produce large and additive effects in the
      onset latencies of lexical decision responses. The influence of these two
      variables was examined in a lexical decision task where continuous arm-reaching
      responses were required and movement trajectories were tracked. The results
      yielded the typical additive pattern of word frequency and stimulus degradation
      on reaction time and movement duration. Importantly, however, an examination of
      movement trajectories revealed interactive effects of word frequency and stimulus
      degradation that emerged for the early part of the movement. These findings
      suggest that factors thought to influence early stages of stimulus identification
      continue to influence the dynamics of the response after response initiation,
      motivating a need to reevaluate current models of lexical decision performance.
      Moreover, this work highlights how the dynamics of naturalistic multidimensional
      responses provide a richer source of information about decision-making processes
      than do discrete unidimensional measures.

PMID- 22419405
TI  - An intellectually disabled patient with the 5q14.3q15 microdeletion syndrome
      associated with an apparently de novo t(2;5)(q13;q14).

PMID- 22419406
TI  - Cellulose-builder: a toolkit for building crystalline structures of cellulose.
AB  - Cellulose-builder is a user-friendly program that builds crystalline structures
      of cellulose of different sizes and geometries. The program generates Cartesian
      coordinates for all atoms of the specified structure in the Protein Data Bank
      format, suitable for using as starting configurations in molecular dynamics
      simulations and other calculations. Crystalline structures of cellulose
      polymorphs Ialpha, Ibeta, II, and III(I) of practically any size are readily
      constructed which includes parallelepipeds, plant cell wall cellulose elementary
      fibrils of any length, and monolayers. Periodic boundary conditions along the
      crystallographic directions are easily imposed. The program also generates atom
      connectivity file in PSF format, required by well-known simulation packages such
      as NAMD, CHARMM, and others. Cellulose-builder is based on the Bash programming
      language and should run on practically any Unix-like platform, demands very
      modest hardware, and is freely available for download from
      ftp://ftp.iqm.unicamp.br/pub/cellulose-builder.

PMID- 22419407
TI  - Late-onset rotator cuff dysfunction after total shoulder arthroplasty--the
      "forgotten" complication. Commentary on an article by Allan A. Young, MD, et al.:
      "Secondary rotator cuff dysfunction following total shoulder arthroplasty for
      primary glenohumeral osteoarthritis: results of a multicenter study with more
      than five years of follow-up".

PMID- 22419408
TI  - Secondary rotator cuff dysfunction following total shoulder arthroplasty for
      primary glenohumeral osteoarthritis: results of a multicenter study with more
      than five years of follow-up.
AB  - BACKGROUND: Secondary rotator cuff dysfunction is a recognized complication
      following shoulder arthroplasty. We hypothesized that the rate of secondary
      rotator cuff dysfunction would increase with follow-up and result in less
      satisfactory clinical and radiographic outcomes. Our aim was to investigate the
      rate of secondary rotator cuff dysfunction following shoulder arthroplasty for
      primary osteoarthritis and identify factors associated with the dysfunction.
      METHODS: Between 1991 and 2003, in ten European centers, 704 total shoulder
      arthroplasties were performed for primary glenohumeral osteoarthritis. Complete
      radiographic and clinical follow-up of more than five years was available for 518
      shoulders. The diagnosis of secondary rotator cuff dysfunction was made when
      moderate or severe superior subluxation of the prosthetic humeral head was
      present on radiographs. Multivariate logistic regression identified factors
      associated with the development of rotator cuff dysfunction. Kaplan-Meier
      survivorship analysis was performed, with the end point being secondary rotator
      cuff failure. Clinical outcome was assessed with use of the Constant score, a
      subjective assessment of the shoulder, and an evaluation of shoulder motion.
      RESULTS: At an average of 103.6 months (range, sixty to 219 months) after
      shoulder arthroplasty, the rate of secondary rotator cuff dysfunction was 16.8%.
      Survivorship free of secondary cuff dysfunction was 100% at five years, 84% at
      ten years, and 45% at fifteen years. Duration of follow-up (p < 0.0001),
      implantation of the glenoid implant with superior tilt (p < 0.001), and fatty
      infiltration of the infraspinatus muscle (p < 0.05) were risk factors for the
      development of secondary cuff dysfunction. Patients with secondary rotator cuff
      dysfunction had significantly worse clinical outcomes (Constant score, subjective
      assessment, and range of motion; p < 0.0001) and radiographic results
      (radiolucent line score, radiographic loosening, glenoid component migration; p <
      0.0001). CONCLUSIONS: In this study, rates of secondary rotator cuff dysfunction
      with moderate or severe superior subluxation of the prosthetic humeral head
      increased with the duration of follow-up and significantly influenced the
      clinical and radiographic outcome of total shoulder arthroplasty performed for
      primary glenohumeral osteoarthritis. Preoperative fatty infiltration of the
      infraspinatus muscle and implantation of the glenoid component with superior tilt
      were prognostic factors.

PMID- 22419410
TI  - Operative versus nonoperative care of displaced midshaft clavicular fractures: a
      meta-analysis of randomized clinical trials.
AB  - BACKGROUND: Recent studies have suggested benefits following primary operative
      fixation of substantially displaced midshaft fractures of the clavicle. We
      reviewed randomized clinical trials of operative versus nonoperative treatment of
      these fractures, and pooled the functional outcome and complication rates to
      arrive at summary estimates of these outcomes. METHODS: A systematic review of
      the literature was performed to identify studies of randomized clinical trials
      comparing operative versus nonoperative care for displaced midshaft clavicular
      fractures. RESULTS: Six studies (n = 412 patients, mean Detsky score = 15.3) were
      included. The nonunion rate was higher in the nonoperatively treated patients
      (twenty-nine of 200) than it was in patients treated operatively (three of 212)
      (p = 0.001). The rate of symptomatic malunion was higher in the nonoperative
      group (seventeen of 200) than it was in the operative group (0 of 212) (p <
      0.001). CONCLUSIONS: Operative treatment provided a significantly lower rate of
      nonunion and symptomatic malunion and an earlier functional return compared with
      nonoperative treatment. However, there is little evidence at present to show that
      the long-term functional outcome of operative intervention is significantly
      superior to nonoperative care.

PMID- 22419411
TI  - An estimate of the number of lives that could be saved through improvements in
      trauma care globally.
AB  - BACKGROUND: Reducing the global burden of injury requires both injury prevention
      and improved trauma care. We sought to provide an estimate of the number of lives
      that could be saved by improvements in trauma care, especially in low income and
      middle income countries. METHODS: Prior data showed differences in case fatality
      rates for seriously injured persons (Injury Severity Score >= 9) in three
      separate locations: Seattle, WA (high income; case fatality 35%); Monterrey,
      Mexico (middle income; case fatality 55%); and Kumasi, Ghana (low income; case
      fatality 63%). For the present study, total numbers of injury deaths in all
      countries in different economic strata were obtained from the Global Burden of
      Disease study. The number of lives that could potentially be saved from
      improvements in trauma care globally was calculated as the difference in current
      number of deaths from trauma in low income and middle income countries minus the
      number of deaths that would have occurred if case fatality rates in these
      locations were decreased to the case fatality rate in high income countries.
      RESULTS: Between 1,730,000 and 1,965,000 lives could be saved in low income and
      middle income countries if case fatality rates among seriously injured persons
      could be reduced to those in high income countries. This amounts to 34-38% of all
      injury deaths. CONCLUSIONS: A significant number of lives could be saved by
      improvements in trauma care globally. This is another piece of evidence in
      support of investment in and greater attention to strengthening trauma care
      services globally.

PMID- 22419412
TI  - Somatostatin analogues for the treatment of enterocutaneous fistulas: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Enterocutaneous fistulas are abnormal connections between the skin
      and gastrointestinal tract that most commonly occur after surgery. Somatostatin
      analogues have been used in their treatment. The objective of the present study
      was to determine if somatostatin analogues shorten the time to closure of
      postoperative enterocutaneous fistulas compared to placebo. METHODS: We searched
      Medline, EMBase, the Cochrane Central Register of Controlled Trials, as well as
      reference lists of textbooks and relevant articles for randomized controlled
      trials (RCT) comparing somatostatin analogues to control in the treatment of
      postoperative enterocutaneous fistulas. We systematically assessed trials for
      eligibility and validity, and extracted data in duplicate. We pooled data across
      studies using a random effects model. RESULTS: Our initial search yielded 720
      studies, of which eight RCT ultimately met eligibility criteria and were included
      in this review. Somatostatin analogues significantly decreased the time to
      closure of fistulas compared to placebo {weighted mean difference (WMD)--6.37
      days [95% confidence interval (CI) -8.33, -4.42]}. The duration of hospital stay
      was also significantly decreased with somatostatin analogue treatment [WMD--4.53
      days (95% CI -8.29, -0.77)]. No difference in mortality was identified with
      somatostatin treatment [RR 0.87 (95% CI 0.49-1.55)]. CONCLUSIONS: Somatostatin
      analogues appear to decrease the duration of enterocutaneous fistulas and
      duration of hospital stay, but no mortality benefit was identified. The quality
      of evidence for outcomes in this review ranged from low to moderate. Future
      large, blinded, RCT would be useful in improving the confidence in the treatment
      effects identified in this systematic review and meta-analysis.

PMID- 22419413
TI  - An estimate of the number of lives that could be saved through improvements in
      trauma care globally.

PMID- 22419414
TI  - Clarifying the links between social support and health: culture, stress, and
      neuroticism matter.
AB  - Although it is commonly assumed that social support positively predicts health,
      the empirical evidence has been inconsistent. We argue that three moderating
      factors must be considered: (1) support-approving norms (cultural context); (2)
      support-requiring situations (stressful events); and (3) support-accepting
      personal style (low neuroticism). Our large-scale cross-cultural survey of
      Japanese and US adults found significant associations between perceived support
      and health. The association was more strongly evident among Japanese (from a
      support-approving cultural context) who reported high life stress (in a support
      requiring situation). Moreover, the link between support and health was
      especially pronounced if these Japanese were low in neuroticism.

PMID- 22419415
TI  - Warning labels formulated as questions positively influence smoking-related risk
      perception.
AB  - Research on warning labels printed on cigarette packages has shown that fear
      inducing health warnings might provoke defensive responses. This study
      investigated whether reformulating statements into questions could avoid
      defensive reactions. Smokers were presented with either warning labels formulated
      as questions, textual warning labels, graphic warning labels, or no warning
      labels. Participants' smoking-related risk perception was higher after exposure
      to warning labels formulated as questions or no warning labels than after
      exposure to textual or graphic warning labels. These results indicate that
      reformulating statements into questions can avoid defensive responses elicited by
      textual- and graphic warning labels.

PMID- 22419416
TI  - Enrollment and participation in a pilot walking programme: the role of self
      efficacy.
AB  - This pilot study investigated the association of self-efficacy with enrollment in
      and compliance with an 8-week exercise trial. We compared self-efficacy levels of
      adults who were eligible but did not enroll (N=221) to those who enrolled (N=115)
      and enrollees who were compliant at the end of the study (N=66). Those in the top
      three self-efficacy quintiles had higher odds of enrollment (adjusted odds ratios
      (AOR)=2.61-2.82) and being compliant at the end of the trial (AOR=4.31-4.38)
      compared to those in the lowest efficacy quintile. These results demonstrated the
      theoretical association between self-efficacy and one's choice of behavior.

PMID- 22419417
TI  - Quality of sexual life in men with obstructive sleep apnoea.
AB  - The study investigated the quality of sexual life of male obstructive sleep
      apnoea patients. Apnoea and non-apnoea participants were assessed with Golombok
      Rust Inventory of Sexual Satisfaction (GRISS) and Structured Clinical Interview
      for DSM-IV (SCID) before the sleep test. Folicule Stimulating Hormone (FSH),
      Luteinising Hormone (LH), prolactin, testosterone and oestrogen levels were also
      evaluated. The apnoea group had a higher BMI and lower LH and testosterone levels
      than the non-apnoea group. There were no differences between the apnoea, non
      apnoea groups and within the apnoea groups (mild, moderate and high apnoea) in
      terms of sexual satisfaction. Although there was a change in the hormonal levels
      of obstructive sleep apnoea patients, the sexual life of apnoea patients was not
      affected at the clinical level.

PMID- 22419418
TI  - The role of acupuncture in cancer supportive care.
AB  - Acupuncture has many beneficial effects during cancer therapy and has proven
      efficacy in the management of side effects induced by chemotherapy and
      radiotherapy. In this review, we discussed the benefits of acupuncture on cancer
      patients. In cancer pain management, acupuncture is effective for head and neck
      pain, waist pain, abdominal and chest pain. Many studies confirm the excellent
      efficacy of acupuncture against symptoms of vomiting and nausea, including those
      induced by chemotherapy and radiotherapy. Head and neck cancer patients receiving
      radiotherapy may develop xerostomia, which may be relieved by acupuncture.
      Acupuncture may also cause sedative and hypnotic effects in cancer patients for
      treating nervousness and insomnia.

PMID- 22419419
TI  - Comprehension of the unique characteristics of traditional Chinese medicine.
AB  - Traditional Chinese Medicine (TCM) has made great contributions to human history,
      especially in China, as has been recorded for thousands of years. The
      characteristics of TCM in both theory and practice make it different from
      Conventional Western Medicine (CWM). The characteristics of TCM include
      phenomenological, philosophical, and methodological aspects. This paper briefly
      discusses some historical turning points and innovations in TCM development in
      China, explores human body enigmas such as the heart, compares different aspects
      of TCM and CWM, and identifies the unique characteristics of TCM treatment, as
      compared to other medical systems.

PMID- 22419420
TI  - Effect of Tai Chi on body balance: randomized controlled trial in elderly men
      with dizziness.
AB  - The purpose of this study was to assess the effect of 18-week Tai Chi training on
      body balance in a dynamic trial among elderly men with dizziness. The study
      covered subjects aged 60 to 80 years. We identified 40 men who reported a history
      of dizziness. The subjects were recruited using direct mailings and a community
      information campaign. The participants were randomly assigned to either the
      exercise intervention (n = 20) or control group (n = 20). The Tai Chi group
      participated in an 18-week exercise class held for 45 minutes twice a week. Body
      balance was studied in two ways: using the "8 foot up and go test" (Rikli and
      Jones 2001) and using a Computer Posturographic System PE 90 (manufactured by
      Military Institute of Aviation Medicine in Warsaw and outfitted with Pro-Med
      modified software). The ability to perform specific tasks (maximal deflections in
      four directions) was measured on the posturographic platform. The variation in
      results obtained on the first and second date of tests in the experimental and
      control groups was confirmed statistically using four parameters, i.e. "8 foot up
      to and go test (H = 8.21;p = 0.003), forward deflection (H = 3.70;p = 0.050),
      backward deflection (H = 5.04;p = 0.024) and maximum sway area (H = 8.86;p =
      0.002). Consequently, we found that the 18-week period of Tai-Chi exercises, with
      a frequency of twice a week for 45 minutes, is beneficial for dynamic balance,
      which is important for the reduction of fall risk factors among elderly men with
      dizziness.

PMID- 22419421
TI  - A systematic review of the effectiveness of qigong exercise in cardiac
      rehabilitation.
AB  - The objective of this study was to assess evidence for the efficacy and
      effectiveness of Chinese qigong exercise in rehabilitative programs among cardiac
      patients. Thirteen databases were searched through to November 2010, and all
      controlled clinical trials on Chinese qigong exercise among patients with chronic
      heart diseases were included. For each included study, data was extracted and
      validity was assessed. Study quality was evaluated and summarized using both the
      Jadad Scale and the criteria for levels of evidence. Seven randomized controlled
      trials (RCTs) and one non-randomized controlled clinical trial (CCT) published
      between 1988 and 2007 met the inclusion criteria. In total, these studies covered
      540 patients with various chronic heart diseases including atrial fibrillation,
      coronary artery disease, myocardial infarct, valve replacement, and ischemic
      heart disease. Outcome measures emerged in these studies included subjective
      outcomes such as symptoms and quality of life; and objective outcomes such as
      blood pressure, ECG findings, and exercise capacity, physical activity, balance,
      co-ordination, heart rate, and oxygen uptake. Overall, these studies suggest that
      Chinese qigong exercise seems to be an optimal option for patients with chronic
      heart diseases who were unable to engage in other forms of physical activity;
      however, its efficacy and effectiveness in cardiac rehabilitation programs should
      be further tested.

PMID- 22419422
TI  - The effects of wet cupping on coronary risk factors in patients with metabolic
      syndrome: a randomized controlled trial.
AB  - High serum cholesterol is an important risk factor for cardiovascular events. It
      has been reported that regular blood donation is associated with a reduction in
      serum cholesterol. This study aimed to determine the effects of wet cupping on
      lipid profiles and anthropometric characteristics of patients with metabolic
      syndrome. One hundred and thirty-six patients aged 18-65 years with metabolic
      syndrome were recruited to participate in this trial. Ten patients were excluded
      due to exclusion criteria. Patients (n = 126) were randomly assigned into the
      control (n = 63) and experimental (n = 63) groups. Patients in the experimental
      group were treated with wet cupping combined with dietary advice. The controls
      were given dietary advice only. Anthropometric and biochemical parameters were
      assessed at baseline and at six and 12 weeks after treatment. The significance of
      the data was analyzed using a repeated measure ANOVA. The lipid profile status
      did not differ significantly between the two groups (p > 0.05) whereas there was
      a significant difference between the two time points within each group (p <
      0.05). In addition, several anthropometric parameters improved in both groups,
      but this did not differ significantly between subject groups. Wet cupping does
      not have a significant effect on anthropometric or biochemical indices compared
      to the effect of dietary advice alone.

PMID- 22419423
TI  - In vitro antioxidant and in vivo anti-inflammatory activities of Ophioglossum
      thermale.
AB  - Antioxidant fractions from Ophioglossum thermale were extracted with five
      different polar solvents using a Soxhlet type extractor. The total phenolic
      content of the extracts was determined by the Folin-Ciocalteu method. The ethyl
      acetate fraction of O. thermale was found to contain maximum phenolics. The dried
      fractions were screened for their antioxidant activity potential using in vitro
      model systems such as 1,1-diphenyl-2-picryl hydrazyl (DPPH), nitroblue
      tetrazolium (NBT) and lipid-peroxidation reduction at different concentrations.
      Results revealed that the EtOAc fraction exhibited the best performance in the
      DPPH assay, NBT assay and lipid peroxidation. All fractions showed more potent
      antioxidant capacity than green tea extract, a well-known antioxidant.
      Furthermore, the EtOAc fraction has the highest total phenolic content (475.65 mg
      of EGCG/g). In addition, the EtOAc fraction at 0.005% and 0.01% (g/100 ml) also
      significantly inhibited UVB irradiation-induced ROS generation in human dermal
      fibroblasts (HDFs). In a carrageenan-induced edema model, the EtOAc fraction
      showed an inhibitory effect (21.5%, p < 0.05) at 200 mg/kg (p.o.) after 300 min
      administration. Consequently, 3-O-methylquercetin (3MQ) was also isolated from
      the antioxidative EtOAc fraction. The data obtained using the above in vitro and
      in vivo tests suggest that the antioxidant activity of O. thermale and its anti
      inflammatory effect on carrageenan-induced acute inflammation can be attributed
      to its ameliorating effect on oxidative damage, and thus it has great potential
      as a source for natural health products. To the best of our knowledge, this is
      the first report on the antioxidant activity of different polar extracts from O.
      thermale.

PMID- 22419424
TI  - The regulatory effect of liuwei dihuang pills on cytokines in mice with
      experimental autoimmune encephalomyelitis.
AB  - The regulatory effect of Liuwei Dihuang Pills (LDP) was studied on cytokines in
      mice with experimental autoimmune encephalomyelitis (EAE), a model for human
      multiple sclerosis (MS), induced by immunization with MOG(35-55) and complete
      Freund's adjuvant (CFA) supplemented with pertussis toxin (PTX). LDP was
      administrated orally for 40 days, and prednisone acetate (PA) was used as a
      control. The pathological changes in the spinal cords of mice were observed by
      light microscope with hematoxylin-eosin (HE) staining and transmission electron
      microscope (TEM). The protein and mRNA expression of tumor necrosis factor-alpha
      (TNF-alpha) and transforming growth factor-beta (TGF-beta) in the spinal cords
      were assessed by immunohistochemistry and RT-PCR assay, and the cyclic adenosine
      monophosphate (cAMP) in mice plasma was measured by radioimmunoassay (RIA) on
      days 12, 25 and 40 post-immunization (PI). The results showed that inflammatory
      cells, demyelination and axonal loss were reduced, and that the protein and mRNA
      expression of TNF-alpha and the ratio of TNF-alpha/TGF-beta were obviously
      decreased, to different extents. However, the levels of cAMP were enhanced in LDP
      treated groups. These findings suggested that LDP regulates the cytokine balance
      in favor of T helper 1 (Th1)/regulatory T (Treg) cells, which depend on
      enhancement of cAMP levels. LDP has a potential role in the treatment of MS and
      other demyelinating diseases of the central nervous system.

PMID- 22419425
TI  - Analysis of the mechanisms underlying the vasorelaxant action of coptisine in rat
      aortic rings.
AB  - The aim of the present study was to evaluate the vasorelaxant effects of
      coptisine and its possible mechanisms in isolated rat aortic rings. Coptisine was
      evaluated on isolated rat aortic rings precontracted with norepinephrine (NE) and
      KCl. The mechanisms were evaluated in the presence or absence of specific
      pharmacological inhibitors. Coptisine (1 ~ 200 MUM) relaxed NE (1 MUM) or KCl (60
      mM) induced sustained contraction with pEC(50) values of 4.49 +/- 0.48 and 4.85
      +/- 0.57 in a concentration dependent manner. Pretreatment with coptisine (10, 50
      or 100 MUM) also inhibited concentration-response curves to NE and KCl. The
      vasorelaxant effect of coptisine was attenuated significantly by endothelium
      removal, and incubation with Nomega-nitro-L-arginine methyl ester (L-NAME, 100
      MUM), methylene blue (10 MUM) and indomethacin (5 MUM) partially reduced the
      vasorelaxant effect of coptisine. In endothelium-denuded rings, the vasorelaxant
      effect of coptisine was reduced significantly by 4-aminopyridine (4-AP, 100 MUM),
      but not glibenclamide (10 MUM) ortetraethylammonium (TEA, 5 mM). Coptisine also
      reduced NE-induced transient contraction in Ca(2+)-free solution, and inhibited
      contraction induced by increasing external calcium in Ca(2+)-free medium plus 60
      mM KCl. It was concluded that coptisine induced both endothelium-dependent and 
      independent relaxation in rat aortic rings. The NO-cGMP mediated pathway may be
      involved in the endothelium-dependent relaxation and in the activation of voltage
      dependent K(+) channels, contributing in part to the endothelium-independent
      relaxation bycoptisine. Coptisine also blocks extracellular Ca(2+) influx by
      interacting with both voltage- and receptor-operated Ca(2+) channels.

PMID- 22419426
TI  - Modified yukmijihwangtang suppresses the production of proinflammatory cytokines
      in the intravesical hydrochloric acid-induced cystitis rat model via the NF
      kappaB pathway.
AB  - Yukmijihwangtang (YM), a boiled extract of medicinal plants, has been prescribed
      for patients with kidney dysfunction in Korea; however, the mechanism underlying
      its therapeutic effects has not been fully elucidated. This study was conducted
      to evaluate the beneficial effects on bladder function by using modified YM (M
      YM), which included Ulmi radicis cortex in addition to the six traditional
      medicinal plants in YM. Bladder irritation of the rats was caused by intravesical
      instillation of HCl. The animals were divided into six groups: sham group,
      cystitis-injury group with no treatment, cystitis-injury group with prednisolone
      treatment (5 mg/kg), and cystitis-injury with M-YM treatment (100, 200 or 500
      mg/kg groups). Whole bladders were collected at day eight after injury. Samples
      were analyzed by histological and immunological examinations. An in vitro study
      was performed to determine whether M-YM extracts inhibit lipopolysaccharide (LPS)
      induced nitric oxide (NO) production and IkappaB phosphorylation in a human
      uroepithelial cell line of T24 cells. Administration of M-YM notably improved
      bladder histological changes, and suppressed IL-6/TNF alpha production and
      IkappaB phosphorylation in a rat model of chronic cystitis. M-YM also inhibited
      LPS-induced NO production and IkappaB phosphorylation in T24 cells. This study
      suggests that administration of M-YM might be an applicable therapeutic
      traditional medicine for the treatment of interstitial cystitis.

PMID- 22419427
TI  - Antioxidant, anti-inflammatory, and antiproliferative activities of Taxillus
      sutchuenensis.
AB  - Inflammation is related to several chronic diseases, including cancer and
      atherosclerosis. Taxillus sutchuenensis (Lecomte) Danser is a special folk
      medicinal plant in Taiwan. The aim of this study was to evaluate the antioxidant,
      anti-inflammatory, and antiproliferative activities of the aqueous-thanol extract
      from T. sutchuenensis (AETS) and its fractions. TEAC, DPPH radicals, total
      phenolic compounds, total flavonoid content, inhibition of NO production in LPS
      induced RAW264.7 cells, and inhibition of cancer cell proliferation were tested.
      Among all fractions, the ethyl-acetate (EA) fraction showed the highest TEAC and
      DPPH radical scavenging activities. The EA fraction also had the highest
      polyphenol and flavonoid content. The EA fractions also decreased LPS-induced NO
      production and the expression of iNOS and COX-2 in RAW264.7 cells. The
      antiproliferative activities of the aqueous/ethanol extract and fractions were
      studied in vitro using A549 cells, and the results were consistent with their
      antioxidant capacities. EA fractions had the highest antiproliferative activity
      with an IC(50) of 454.38 +/- 1.48 MUg/ml. Quercetin also had antioxidant, anti
      inflammatory, and antiproliferative activities. Quercetin might be an important
      bioactive compound in T. sutchuenensis. The experimental data indicated that T.
      sutchuenensis is a potent antioxidant medicinal plant, and such efficacy may be
      mainly attributed to its polyphenolic compounds.

PMID- 22419428
TI  - In vitro antioxidant and antimicrobial activity of extracts from Morus alba L.
      leaves, stems and fruits.
AB  - In this study, the aqueous and ethanolic extracts (leaves, stems and fruits) from
      Morus alba L., a traditional Chinese medicine, were evaluated for their
      antioxidant and antimicrobial properties. Ethanolic extracts showed higher
      contents of both total phenolics and flavonoids than aqueous extracts. The total
      phenolic content was in the order of: leaf extracts > fruit extracts > stem
      extracts, whereas the total flavonoids was: leaf extracts > stem extracts > fruit
      extracts. Using DPPH assays, the concentrations providing 50% inhibition (IC(50))
      values of aqueous extracts from leaves, stems and fruits were 7.11 +/- 1.45
      mg/ml, 86.78 +/- 3.21 mg/ml and 14.38 +/- 2.83 mg/ml, respectively, whereas the
      IC(50) values of ethanolic extracts were 3.11 +/- 0.86 mg/ml, 14.62 +/- 2.45
      mg/ml and 12.42 +/- 2.76 mg/ml, respectively. In sum, the antioxidant activities
      of ethanolic extracts from M. alba L. were stronger than the aqueous extracts,
      and in the order of: leaf extracts > fruit extracts > stem extracts. The
      ethanolic extracts exhibited moderate antimicrobial activities, whereas the
      aqueous extracts showed poor antimicrobial properties in our test system. This
      study validated the medicinal potential of M. alba L.

PMID- 22419429
TI  - Ethanol extract of Graptopetalum paraguayense upregulates paraoxonase 1 gene
      expression via an AKT/NF-kappaB-dependent pathway.
AB  - Human serum paraoxonase 1 (PON1), a calcium-dependent ester hydrolase, protects
      against the oxidative modification of low-density lipoprotein (LDL) and is a
      major anti-atherosclerotic component of high-density lipoprotein (HDL).
      Graptopetalum paraguayense, a folk herbal medicine commonly used in Taiwan, has
      antioxidative, anti-inflammatory, anti-hypertensive, and anti-atherogenic
      properties. The effects of G. paraguayense on the activity and/or expression of
      PON1 were examined using various extracts of the plant; extracts were made in
      water (GPWE), 50% ethanol (GP50E), and 95% ethanol (GP95E). Of these extracts,
      GP50E was found to be the most effective at increasing the function and
      expression of PON1 in a human hepatoma HepG2 cell line. Data from electrophoretic
      mobility shift assays and promoter-reporter luciferase analyses demonstrated that
      the DNA binding activity and transactivation ability of NF-kappaB were enhanced
      by GP50E. Treatment with NF-kappaB inhibitors, pyrrolidine dithiocarbamate, and
      BAY 11-7082 significantly attenuated GP50E-induced PON1 production and NF-kappaB
      transactivation activity. In addition, GP50E increased the levels of
      phosphorylated protein kinase B (PKB/AKT). Pharmacological inhibition of AKT by
      LY294002 effectively suppressed NF-kappaB activation and PON1 gene expression,
      suggesting that AKT was an upstream regulator of GP50E-mediated biological
      events. Overall, the results show that GP50E up-regulated PON1 gene expression
      via an AKT/NF-kappaB-dependent signaling pathway in human hepatoma HepG2 cells.
      This observation led to the conclusion that the anti-atherogenic characteristics
      of G. paraguayense are modulated, at least in part, via the up-regulation of
      hepatocyte PON1 gene expression.

PMID- 22419430
TI  - Gleditsia sinensis thorn extract inhibits proliferation and TNF-alpha-induced MMP
      9 expression in vascular smooth muscle cells.
AB  - The thorns of Gleditsia sinensis, which are extensively used as a medicinal herb
      in Asian countries, have been reported to exert various pharmacological effects.
      However, the anti-atherogenic effect of Gleditsia sinensis thorns has never been
      investigated. In the present study, we investigated the role and effect of the
      ethanol extract of Gleditsia sinensis thorns (EEGS) on cultured vascular smooth
      muscle cells (VSMC). Treatment of VSMC with EEGS led to a significant decrease in
      cell growth by arresting cells in the G2/M-phase of the cell cycle, which was
      associated with up-regulated p21WAF1 levels and suppression of G2/M cell cycle
      regulators, cyclinB1, Cdc2 and Cdc25c. In addition, EEGS treatment led to the
      induction of extracellular signal-regulated kinase1/2 (ERK1/2), p38 MAPK, and JNK
      (c-Jun N-terminal kinases) activation. EEGS-induced p21WAF1 expression was
      blocked by treatment with the p38 MAPK-specific inhibitor SB203580. SB203580 also
      markedly recovered the inhibition of cell growth and decrease in cell cycle
      proteins in EEGS-treated VSMC. Moreover, EEGS inhibited matrix metalloproteinase
      9 (MMP-9) expression induced by tumor necrosis factor-alpha (TNF-alpha) in VSMC.
      Finally, an electrophoresis mobility shift assay demonstrated that EEGS
      suppressed expression of transcription factor, nuclear factor kappaB (NF-kappaB)
      and activator protein-1 (AP-1), which are essential cis-elements for the MMP-9
      promoter in TNF-alpha-treated VSMC. These results demonstrate that EEGS exerts a
      potent inhibitory effect on cell proliferation and MMP-9 expression in VSMC.
      These unexpected novel findings represent theoretical data for the preventive and
      therapeutic use of EEGS for the treatment of atherosclerosis disease.

PMID- 22419431
TI  - Preventive effects of beta-thujaplicin against UVB-induced MMP-1 and MMP-3 mRNA
      expressions in skin fibroblasts.
AB  - Solar UV radiation damages human skin by affecting skin tone and resiliency and
      leads to premature aging (photoaging). The skin damage is caused by the
      activation of the AP-1 transcription factor, which increases matrix
      metalloproteinase (MMP) expression and collagen degradation. An increase of
      interleukin (IL)-6 is also correlated with the activation of MMP-1 expression.
      beta-thujaplicin has shown both acaricidal and antimicrobial activities. Also,
      beta-thujaplicin has been shown to be protective against apoptosis due to the
      oxidative effects of UV irradiation. However, the effect of beta-thujaplicin on
      UVB-induced MMPs had not been investigated. In this study, after UVB exposure,
      MMP-1 and IL-6 production in human skin fibroblasts was examined in the presence
      of beta-thujaplicin, vitamin C, and vitamin E. The expression of MMP-1, MMP-3,
      tissue inhibitor of metalloproteinase (TIMP-1, TIMP-3) and procollagen mRNA was
      also investigated. Results showed that UVB-induced MMP-1 production was
      suppressed by the beta-thujaplicin treatment in a dose-dependent manner, but not
      by vitamin C and vitamin E. beta-thujaplicin also prevented the up-regulation of
      MMP-1 and MMP-3 mRNA. Moreover, the UVB-suppressed procollagen gene expression
      was restored to normal by beta-thujaplicin. Neither UVB nor beta-thujaplicin
      affected the mRNA expression of TIMP-1 and TIMP-3. The IL-6 production induced by
      UVB was lower in beta-thujaplicin treated fibroblasts than in the controls. In
      conclusion, this study shows the capability of beta-thujaplicin in preventing MMP
      1 production due to UVB irradiation via inhibition of MMP gene expression.
      Importantly, the UVB-suppressed procollagen gene expression can be restored to
      normal by beta-thujaplicin. These findings indicate that beta-thujaplicin is a
      promising and potent agent to inhibit UVB-induced MMP-1 and MMP-3 gene expression
      in skin fibroblasts.

PMID- 22419432
TI  - Cytotoxic effect of Eucalyptus citriodora resin on human hepatoma HepG2 cells.
AB  - The aim of this study was to evaluate the antiproliferative effect of Eucalyptus
      citriodora resin (ECR) on human hepatoma HepG2 cells. The results from MTT assay
      and LDH leakage analysis showed that water extracts of ECR (WEECR) in the dose
      range of 0-500 MUg/ml displayed stronger cytotoxic effects on HepG2 cells than
      other organic solvent extracts of ECR. By flow cytometry analysis, WEECR slowed
      down the cell cycle at the G0/G1 phase after 24 h of incubation. Moreover, WEECR
      treatment induced an apoptotic response in HepG2 cells. WEECR-induced apoptosis
      was in association with the attenuation of mitochondrial transmembrane potentials
      (DeltaPsi(m)), increased Bax/Bcl-2 ratio and activation of caspase-3. In
      addition, WEECR contained high concentration of phenolics and flavonoids, which
      may be responsible for the potent cytotoxicity of WEECR on HepG2 cells. Taken
      together, WEECR may be a potent antihepatoma agent due to apoptosis in HepG2
      cells.

PMID- 22419433
TI  - Functional role of wogonin in anti-angiogenesis.
AB  - Constitutive activation of the Janus kinase (JAK)/signal transducer and activator
      of transcription (STAT) pathway occurs commonly in cancer cells and endothelial
      cells, and contributes to angiogenesis. Wogonin is a compound with many
      biologically relevant properties. We previously reported that wogonin blocked IL
      6-induced angiogenesis through suppression of VEGF expression, an important
      regulator of angiogenesis. However, the pathway involved in the suppressive
      effect of wogonin on IL-6-induced VEGF has not been completely clarified. This
      study aimed to investigate the molecular mechanisms participating in the
      suppression of wogonin on IL-6-induced VEGF in vitro, focusing on IL
      6R/JAK1/STAT3/VEGF pathway. Both STAT3 siRNA and wogonin treatment resulted in an
      abolition of the expression of VEGF. Moreover, our data revealed that wogonin
      treatment after STAT3 knock-down did not further suppress VEGF expression. The
      addition of IL-6R siRNA or wogonin resulted in a decrease in the expression level
      of the phosphorylated JAK1 protein. Furthermore, wogonin significantly decreased
      the amount of phosphorylated STAT3. Finally, by EMSA, wogonin suppressed IL-6
      induced STAT3 binding activity in a concentration-dependent manner. Taken
      together, our results show that wogonin suppresses IL-6-induced VEGF by
      modulating the IL-6R/JAK1/STAT3 signaling pathway. Based on this study, we
      suggest that wogonin may provide a new potential therapeutic option for treatment
      of IL-6-related pathological angiogenesis.

PMID- 22419434
TI  - Podcasting as a goal oriented toy in education.

PMID- 22419435
TI  - Understanding self-assessment as an informed process: residents' use of external
      information for self-assessment of performance in simulated resuscitations.
AB  - Self-directed learning requires self-assessment of learning needs and
      performance, a complex process that requires collecting and interpreting data
      from various sources. Learners' approaches to self-assessment likely vary
      depending on the learner and the context. The aim of this study was to gain
      insight into how learners process external information and apply their
      interpretation of this information to their self-assessment and learning during a
      structured educational activity. The study combined quantitative performance data
      with qualitative interview data. Pediatric residents led video-recorded simulated
      resuscitations and rated their crisis resource management skills on a validated 6
      item instrument. Three independent observers rated the videos using the same
      instrument. During semi-structured interviews, each resident reviewed the video,
      rerated performance, discussed the self-assessment process, and interpreted
      feedback and observer scores. Transcripts were analyzed for themes. Sixteen
      residents participated. Residents' self-assessed scores ranged widely but usually
      fell within two points of the observers. They almost universally lowered their
      scores when self-assessing after the video review. Five major themes emerged from
      qualitative analysis of their interviews: (1) residents found self-assessment
      important and useful in certain contexts and conditions; (2) residents varied in
      their self-directed learning behaviors after the simulated resuscitation; (3)
      quantitative observer assessment had limited usefulness; (4) video review was
      difficult but useful; and (5) residents focused on their weaknesses and felt a
      need for constructive feedback to enhance learning. The residents in our study
      almost uniformly embraced the importance of self-assessment for all medical
      professionals. Even though video review had a negative impact on their self
      assessment scores and was perceived as painful, residents saw this as the most
      useful aspect of the study exercises residents. They were less accepting of the
      quantitative assessment by observers. Residents explained their tendency to focus
      on weaknesses as a way to create an incentive for learning, demonstrating that
      self-assessment is closely linked to self-directed learning. How learners can use
      video review and external assessment most effectively to guide their self
      directed learning deserves further study.

PMID- 22419436
TI  - Nitrogen-doped carbon monolith for alkaline supercapacitors and understanding
      nitrogen-induced redox transitions.
AB  - A nitrogen-doped porous carbon monolith was synthesized as a pseudo-capacitive
      electrode for use in alkaline supercapacitors. Ammonia-assisted carbonization was
      used to dope the surface with nitrogen heteroatoms in a way that replaced carbon
      atoms but kept the oxygen content constant. Ammonia treatment expanded the
      micropore size-distributions and increased the specific surface area from 383
      m(2) g(-1) to 679 m(2) g(-1). The nitrogen-containing porous carbon material
      showed a higher capacitance (246 F g(-1)) in comparison with the nitrogen-free
      one (186 F g(-1)). Ex situ electrochemical spectroscopy was used to investigate
      the evolution of the nitrogen-containing functional groups on the surface of the
      N-doped carbon electrodes in a three-electrode cell. In addition, first
      principles calculations were explored regarding the electronic structures of
      different nitrogen groups to determine their relative redox potentials. We
      proposed possible redox reaction pathways based on the calculated redox affinity
      of different groups and surface analysis, which involved the reversible
      attachment/detachment of hydroxy groups between pyridone and pyridine. The
      oxidation of nitrogen atoms in pyridine was also suggested as a possible reaction
      pathway.

PMID- 22419438
TI  - Microbial manipulation of host sex determination. Endosymbiotic bacteria can
      directly manipulate their host's sex determination towards the production of
      female offspring.
AB  - A recent study in the lepidopteran Ostrinia scapulalis shows that endosymbionts
      can actively manipulate the sex determination mechanism of their host. Wolbachia
      bacteria alter the sex-specific splicing of the doublesex master switch gene. In
      ZZ males of this female heterogametic system, the female isoform of doublesex is
      produced in the presence of the bacteria. The effect is a lethal feminization of
      genotypic males. Curing of ZW females leads to males that die, indicating that
      the bacteria have an obligate role in proper sex determination and development of
      their host. Microbial intervention with host sex determination may be a driving
      force behind the evolutionary turnover of sex determination mechanisms.

PMID- 22419437
TI  - Frozen-thawed embryo transfer cycles in China: clinical outcomes of two and three
      multicellular embryos transfers.
AB  - PURPOSE: To analyze the clinical outcomes of frozen embryo transfer (FET) cycles
      when two or three multicellular embryos were transferred in Chinese women.
      METHODS: A retrospective study was conducted to analyze 980 FET cycles performed
      between January 2007 and October 2010. Two (785 cycles) or three (195 cycles)
      multicellular embryos were transferred. RESULTS: Both in patients under 35 years
      (n = 776) and those aged 35 to 39 years (n = 169), the transfer of two versus
      three multicellular embryos results in similar clinical pregnancy rates (CPR),
      implantation rates (IR) and live birth rates (LBR). In both age groups, the
      multiple pregnancy rate (MPR) was significantly higher in the three-embryo
      groups. Among women over 40 years of age (n = 35), there were no differences in
      the CPR, IR, MBR or LBR between the two groups CONCLUSIONS: Transferring two
      instead of three multicellular embryos in patients under 40 years old
      significantly decreases the risk of MPR without compromising PR, IR and LBR. In
      the age group above 40, transferring two instead of three multicellular embryos
      did not decrease PR, IR, MBR or LBR. Transferring more embryos when a patient had
      more unsuccessful cycles was not warranted in all patients.

PMID- 22419439
TI  - Basaloid squamous cell carcinoma of the esophagus.
AB  - PURPOSE: Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare
      carcinoma with distinct characteristics. No standard treatment has been
      established. This retrospective study was designed to investigate the clinical
      and pathological characteristics, diagnosis, treatment, and prognosis of
      esophageal BSCC. METHODS: Clinical data were retrospectively analyzed from 26
      patients with pathologically confirmed esophageal BSCC who underwent
      transthoracic esophagectomy with lymphadenectomy between January 1995 and June
      2010 at the Cancer Hospital of Shantou University Medical College.
      Clinicopathologic data between BSCC patients and different histologic grades of
      esophageal squamous cell carcinoma (ESCC) patients were statistically compared by
      means of the chi(2) test or Fisher's exact test. The Kaplan-Meier and log-rank
      methods were used to estimate and compare survival rates. RESULTS:
      Microscopically, BSCC was characterized by a nesting, lobular, or trabecular
      arrangement of small crowded cells with scant cytoplasm. None of the histologic
      specimens taken at preoperative esophagoscopy were diagnosed as BSCC. The median
      survival time (MST) of the 26 patients was 29.0 months (95% confidence interval,
      9.0-49.0), and the 1-, 3-, and 5-year overall survival rates were 73.1, 42.7, and
      36.6%, respectively. The MST for BSCC patients was significantly lower than that
      of well-differentiated SCC patients (P = 0.024), but there were no significant
      differences between the MST for BSCC patients and that of moderately or poorly
      differentiated SCC patients (P > 0.05). CONCLUSIONS: BSCC of the esophagus is a
      rare but distinctive disease and is prone to be misdiagnosed by endoscopic
      biopsy. The prognosis is poorer than well-differentiated SCC, but similar to
      moderately or poorly differentiated SCC.

PMID- 22419440
TI  - Analysis of molecular cytogenetic alterations in uterine leiomyosarcoma by array
      based comparative genomic hybridization.
AB  - OBJECTIVE: The aim of this study was to identify novel genes following genomic
      DNA copy number changes using a genome-wide array-based comparative genomic
      hybridization (array-CGH) analysis in uterine leiomyosarcoma (ULMS). METHODS:
      Genomic DNA copy number changes were analyzed in 15 cases of ULMS from St Mary's
      Hospital of the Catholic University of Korea. The paraffin-fixed tissue samples
      were micro-dissected under microscope, and DNA was extracted. Array-based CGH and
      genomic polymerase chain reaction were carried out with statistical analyses such
      as hierarchical clustering and Gene Ontology. RESULTS: All of 15 cases of ULMS
      showed specific gains and losses. The percentage of average gains and losses were
      8.4 and 16.6 %, respectively. The analysis limit of average gains and losses was
      40 %. The regions of high level of gain were 1q23.3, 7p14.2, 7q34, 7q35, 7q36.3,
      13q34, and 16p13.3. And the regions of homozygous loss were 2q21.1, 2q22.1,
      2p23.2, 12q23.3, 4q21.22, 4q34.3, 11q24.2, 12q23.3, 13q13.1, 13q21.33, and
      14q24.3. In ULMS samples, recurrent regions of gain were 1p36.33, 1p36.32,
      5q35.3, 7q36.3, and 8q24.3 and recurrent regions of loss were 1p31.1-p31.3,
      1p32.1-p32.3, 2p12, 2p13.3, 2p14, 2p16.2-p16.3, 2q12.1-q12.3, 2q21.1-q21.2,
      2q22.2-q22.3, 2q34, 2q36.1-q36.3, 5q21.3, 5q23.3, 5q31.1, 6p11.2, 6p12.1,
      10q11.23, 10q21.2-q21.3, 10q23.2, 10q23.31, 10q25.1-q25.2, 10q25.3, 10q26.13,
      10q26.2-q26.3, 11p11.2, 11p11.12, 11p12, 11p13, 11p15.4, 11q23.1-q23.2, 11q23.3,
      13q14.12, 13q14.13-13q14.2, 13q14.2, 13q14.2, 13q14.3, 13q21.33, 13q22.1-q22.3,
      14q24.2, 14q24.3, 14q31.1, 14q32.33, 15q11.2-q13, 15q14, 16q22.3, 16q23.1,
      16q23.2, 16q24.1, 20p12.1, and 21q22.3. Representative frequently gained BAC
      clones encoded genes were HDAC9, CRR9, SOX18, PTPRN2, SKI, SOLH, and KIAA1199.
      The genes encoded by frequently lost BAC clones were LOC150516 and AMY2A. A
      subset of cellular processes from each gene were clustered by Gene Ontology
      database. CONCLUSIONS: The present study using array-CGH analyses sought a deeper
      elucidation of the specific genomic alterations related to ULMS. The high
      resolution of array-CGH combined with human genome database would give a chance
      at identifying relevant target genes.

PMID- 22419441
TI  - Circulating endothelial cells and their apoptotic fraction are mutually
      independent predictive biomarkers in Bevacizumab-based treatment for advanced
      colorectal cancer.
AB  - BACKGROUND: Bevacizumab has shown consistent clinical efficacy in metastatic
      colorectal cancer (mCRC), but some patients respond better than others. Thus, it
      is crucial to identify biomarkers that permit the recognition of potentially
      responsive subjects and to spare toxicity in those who are unlikely benefit from
      treatment. METHODS: In 24 mCRC patients undergoing Bevacizumab-based first-line
      treatment, we assessed by multiparameter flow cytometry changes in circulating
      endothelial cell (CEC) number, their apoptotic fraction (APO-CEC) and their
      mutual relationship. Data were compared with those from a group of 21 healthy
      subjects. RESULTS: CECs and APO-CECs were higher in patients versus controls (p =
      0.01 and p > 0.05, respectively). The increase in CECs at the 3rd cycle in
      complete response (CR) patients was statistically significant (p = 0.048). A
      better progression-free survival was evidenced in patients that showed an
      increase in CECs at the 6th cycle (p = 0.009). Regarding the changes in CECs and
      APO-CECs, a strong correlation was evidenced, at baseline, both in the global
      population (0.002; r: 0.53) and in the CR subgroup (p: 0.02; r: 0.77). In the
      partial response + stable and progression disease (SD + PD) subgroup, this
      correlation was highly significant at the 6th cycle (p: 0.001; r: 0.83).
      CONCLUSIONS: We confirmed the predictive role of an increase in CECs in mCRC
      patients treated with Bevacizumab-based therapy and showed that modifications in
      CECs and APO-CECs are independent factors. This underlines the relevance of a
      simultaneous quantitative and functional evaluation of these biomarkers in view
      of their possible diagnostic utility.

PMID- 22419442
TI  - Right temporoparietal junction and attentional reorienting.
AB  - The interaction between goal-directed and stimulus-driven attentional control
      allows humans to rapidly reorient to relevant objects outside the focus of
      attention--a phenomenon termed contingent reorienting. Neuroimaging studies have
      observed activation of the ventral and dorsal attentional networks, but specific
      involvement of each network remains unclear. The present study aimed to determine
      whether both networks are critical to the processes of top-down contingent
      reorienting. To this end, we combined the contingent attentional capture paradigm
      with the use of transcranial magnetic stimulation (TMS) to interfere with
      temporoparietal junction (TPJ; ventral network) and frontal eye field (dorsal
      network) activity. The results showed that only right TPJ (rTPJ) TMS modulated
      contingent orienting. Furthermore, this modulation was highly dependent on visual
      fields: rTPJ TMS increased contingent capture in the left visual field and
      decreased the effect in the right visual field. These results demonstrate a
      critical involvement of the ventral network in attentional reorienting and reveal
      the spatial selectivity within such network.

PMID- 22419443
TI  - Brief communication: Reevaluating osteoporosis in human ribs: the role of
      intracortical porosity.
AB  - Osteoporosis is a major health concern in modern society and is continually being
      evaluated in past populations by quantifying bone loss. Cortical area measures
      are commonly used in anthropological analyses to assess bone loss in the ribs,
      but these values are typically based on endosteal expansion and do not account
      for intracortical bone loss. The objective of this study is to evaluate the
      effectiveness of using absolute cortical area, compared to traditional cortical
      area measures to describe global bone loss in elderly ribs. Transverse sections
      were prepared from sixth ribs of ten elderly subjects, and bone area measurements
      were made from 100* magnification composites of each rib for calculation of
      cortical area (Ct.Ar) and percent cortical area (% C/T). In addition, all areas
      of intracortical porosity were measured and percent porosity area (% Po.Ar)
      calculated. Absolute cortical area (Ct.Ar(A)) was calculated by subtracting
      porosity area from cortical area, and a percent absolute cortical area (% C(A)/T)
      calculated. ANOVA results reveal significant interindividual variation in percent
      porosity area (% Po.Ar). Percent cortical area and percent absolute cortical area
      values were compared and results show a mean difference of 4.08% exists across
      all subjects, with a range of 1.19-11.73%. This suggests that intracortical
      porosity is variable and does play a role in age-associated bone loss in the rib.
      All future investigations of osteoporosis should account for intracortical
      porosity in bone loss.

PMID- 22419445
TI  - Diet in acne: further evidence for the role of nutrient signalling in acne
      pathogenesis.
AB  - Recent evidence underlines the role of Western diet in the pathogenesis of acne.
      Acne is absent in populations consuming Palaeolithic diets with low glycaemic
      load and no consumption of milk or dairy products. Two randomized controlled
      studies, one of which is presented in this issue of Acta Dermato-Venereologica,
      have provided evidence for the beneficial therapeutic effects of low glycaemic
      load diets in acne. Epidemiological evidence confirms that milk consumption has
      an acne-promoting or acne-aggravating effect. Recent progress in understanding
      the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1)
      allows a new view of nutrient signalling in acne by both high glycaemic load and
      increased insulin-, IGF-1-, and leucine signalling due to milk protein
      consumption. Acne should be regarded as an mTORC1-driven disease of civilization,
      like obesity, type 2 diabetes and cancer induced by Western diet. Early dietary
      counselling of teenage acne patients is thus a great opportunity for dermatology,
      which will not only help to improve acne but may reduce the long-term adverse
      effects of Western diet on more serious mTORC1-driven diseases of civilization.

PMID- 22419446
TI  - Long-term survival in infantile malignant autosomal recessive osteopetrosis
      secondary to homozygous p.Arg526Gln mutation in CLCN7.
AB  - Infantile malignant autosomal recessive osteopetrosis (ARO; OMIM 259700) has been
      reported to be associated with mutations in TCIRG1, CLCN7, or OSTM1. ARO caused
      by homozygous (or compound heterozygous) mutations in CLCN7, as described here,
      is usually diagnosed at birth or early in infancy due to generalized
      osteosclerosis and severe hematologic deficits. The maximal life expectancy of
      patients with ARO in the absence of bone marrow transplantation is thought to be
      10 years. We report on a 25-year-old Thai man who is affected with ARO. Clinical
      features include proportionate short stature, vision impairment, esotropia,
      exophthalmos, mild hearing loss, and hepatosplenomegaly. Pancytopenia was present
      and the patient had frequent illnesses. Radiographs showed generalized
      osteosclerosis with almost no visible of bone marrow spaces. Dense maxilla and
      mandible with impacted and malformed teeth were observed. Multiple fractures were
      reported. He developed osteomyelitis of the mandible on four separate occasions,
      and partial mandibulectomy was performed. Molecular studies showed that there
      were no pathogenic mutations in TCIRG1. However, mutation analysis of CLCN7
      revealed a homozygous missense mutation (p.Arg526Gln). This patient is, it
      appears, the longest lived individual with ARO ever reported. Evaluation of
      osteoclastogenesis in our patient demonstrated very large immature osteoclasts
      with a high number of nuclei.

PMID- 22419447
TI  - International migration and educational assortative mating in Mexico and the
      United States.
AB  - This paper examines the relationship between migration and marriage by describing
      how the distributions of marital statuses and assortative mating patterns vary by
      individual and community experiences of migration. In Mexico, migrants and those
      living in areas with high levels of out-migration are more likely to be in
      heterogamous unions. This is because migration increases the relative
      attractiveness of single return migrants while disproportionately reducing the
      number of marriageable men in local marriage markets. In the United States, the
      odds of homogamy are lower for migrants compared with nonmigrants; however, they
      do not vary depending on the volume of migration in communities. Migrants are
      more likely than nonmigrants to "marry up" educationally because the relatively
      small size of this group compels them to expand their pool of potential spouses
      to include nonmigrants, who tend to be better educated than they are. Among
      migrants, the odds of marrying outside of one's education group increase the most
      among the least educated. In Mexican communities with high rates of out
      migration, the odds of marrying outside of one's education group are highest
      among those with the highest level of education. These findings suggest that
      migration disrupts preferences and opportunities for homogamy by changing social
      arrangements and normative climates.

PMID- 22419448
TI  - Susceptibility loci affecting ERBB2/neu-induced mammary tumorigenesis in mice.
AB  - Twenty percent of breast cancers exhibit amplification or overexpression of
      ERBB2/neu and a poor prognosis. As the susceptibility genes controlling ERBB2
      tumorgenesis are unknown, in a genetic mapping project we crossed transgenic mice
      expressing the neu oncogene under control of MMTV promoter with recombinant
      congenic (RC) strains, which provided a high mapping power. RC strains differed
      considerably in tumor latency (P = 0.0002), suggesting a strong genetic control
      of tumor development. Linkage analysis in neu-transgene carrying F2 hybrids
      between the most susceptible and most resistant RC strain revealed three mammary
      tumor susceptibility (Mts) loci with main effects, Mts1 (chr. 4), Mts2 (chr. 10),
      Mts3 (chr. 19), and two interacting loci Mts4 (chr.6) and Mts5 (chr. 8),
      significantly affecting mammary tumor latency. Suggestive significance levels
      indicated control of tumor numbers by Mts1 alone and in interaction with Mts5,
      and by two additional interacting loci on chromosomes 1 and 8. These loci
      combined explain to a large extent the tumor latency and number in individual F2
      mouse. We also identified a suggestive locus on chromosome 17 controls metastasis
      to the lung. The loci Mts1, Mts1b, and Mts3 are located in the Naad4-4,5 and
      Naad19-2 LOH-regions of neu-induced mammary tumors, corresponding to the frequent
      human breast cancer LOH-regions 1p34/1p36, and 10q25, respectively. These results
      expand the knowledge of ERBB2 tumorigenesis and point to a combined control of
      specific tumor phenotypes by germ-line polymorphisms and somatic alterations.

PMID- 22419449
TI  - Normative data and longitudinal invariance of the Life Engagement Test (LET) in a
      community sample of older adults.
AB  - PURPOSE: Interest in evaluating purpose in life as an important component of
      ageing well is growing; however, investigation into the appropriate measurement
      of this construct is required. The purpose of this paper was to examine the
      measurement properties of the Life Engagement Test (LET) and to provide normative
      data for a non-clinical sample of community-dwelling older adults. METHODS: A
      random sample of 545 adults, aged 55-94 years, completed the LET twice over a 12
      month period as part of a larger survey on relocation in later life. RESULTS:
      Consistent with previous research, participants typically reported high levels of
      purpose in life. Scores were also observed to vary over the 12-month duration,
      with, on average, an increase in purpose in life at Time 2. However, tests of
      longitudinal invariance were inconclusive. CONCLUSIONS: Future research is needed
      to further examine the content validity of the LET, and its factorial invariance
      over longer measurement intervals, and across different populations including non
      residential/aged care settings.

PMID- 22419450
TI  - The patient-physician relationship in patients with breast cancer: influence on
      changes in quality of life after rehabilitation.
AB  - PURPOSE: The objective of this study was to examine whether aspects of the
      patient-physician relationship for breast cancer patients have an influence on
      the change in health-related quality of life (HRQOL) after inpatient
      rehabilitation. METHODS: N = 329 breast cancer patients undergoing inpatient
      rehabilitation in Germany were surveyed using questionnaires at the beginning of
      rehabilitation, end of rehabilitation, and 6 months after rehabilitation.
      Multiple imputations and multilevel models of change were used in the data
      analyses. RESULTS: Even after comprehensive adjustment for sociodemographic,
      medical, psychological variables, and center effects, aspects of the physician
      patient relationship were statistically and clinically relevant predictors of
      HRQOL after rehabilitation. Satisfaction with physician's care appears to have a
      rather short-term effect, but the effect of promoting patient participation can
      still be partially determined 6 months after rehabilitation. Other important
      predictors of HRQOL improvement are optimism, higher level of education, higher
      income, living with a partner, and the ability to work. CONCLUSIONS: By taking
      into consideration the patient's communication and participation needs,
      physicians can contribute to an improved HRQOL after rehabilitation. The high
      predictive power of socioeconomic factors shows that rehabilitation care can be
      more effective if it accounts for the specific situation of socially
      disadvantaged individuals.

PMID- 22419451
TI  - The association of self-rated health and lifestyle behaviors among foreign-born
      Chinese, Korean, and Vietnamese Americans.
AB  - PURPOSE: This study employed the 2009 California Health Interview Survey to
      examine the association of self-rated heath status and lifestyle behavior
      variables such as smoking at least 100 cigarettes or more in an entire lifetime,
      alcohol consumption, and physical activity level among foreign-born Chinese,
      Korean, and Vietnamese Americans aged 18 and older. METHODS: The total study
      sample consisted of 3,023 foreign-born adult Chinese (n = 812), Korean (n = 857),
      and Vietnamese (n = 1,354) Americans. Logistic regression via Stata 12 was
      employed. Odds ratios (OR) along with confidence intervals (CI) were reported in
      the results. RESULTS: Results revealed that smoking at least 100 cigarettes or
      more in an entire lifetime had a negative association with good health status (OR
      = 0.74, 95 % CI = 0.59, 0.94), while alcohol consumption had a positive
      association with good health status (OR = 1.20, 95 % CI = 1.00, 1.44). Moderate
      physical activity (OR = 1.26, 95 % CI = 1.05, 1.50) and vigorous physical
      activity (OR = 1.68, 95 % CI = 1.31, 2.15) had a similar positive association
      with good self-rated health status. The results also revealed that the predicted
      probability of self-rated health status based on ethnicity and lifestyle
      variables was more favorable for foreign-born Chinese Americans than their Korean
      and Vietnamese American counterparts. CONCLUSIONS: This study's results
      corroborated the findings reported in previous research on the association of
      lifestyle behaviors and health status. Regardless of racial or ethnic
      backgrounds, good lifestyles have an important role in the prevention of poor
      health status. However, health education and lifestyle intervention programs
      should take cultural differences among racial and ethnic populations into
      consideration.

PMID- 22419452
TI  - Predicting the health economic performance of new non-fusion surgery in
      adolescent idiopathic scoliosis.
AB  - Adolescent idiopathic scoliosis (AIS) can lead to pain, impaired spinal function,
      and socio-psychological problems. Conventional surgical treatment of severe forms
      of AIS fuses the vertebrae, thereby restricting spinal function and growth of the
      adolescents. Non-fusion surgical treatment (NFS) is being proposed to prevent
      these drawbacks. To support the further development of NFS, this study aims to
      predict the health economic performance of the new NFS treatment and compare it
      with standard AIS treatment. A decision tree was constructed to compare NFS with
      bracing, possibly followed by posterior fusion surgery. The outcome measures were
      quality of life, complications, and costs. The Analytic Hierarchy Process (AHP),
      a technique for multi-criteria decision analysis, supported an expert panel of
      biomedical engineers and orthopaedic surgeons to predict the missing NFS
      performance data in the decision tree. The decision tree analysis showed that NFS
      is the preferred form of treatment in patients prone to disease progression. The
      advantages are its positive effect on spinal function and the self-esteem of the
      patient. Future clinical acceptance of NFS can be supported by reduced costs and
      an optimization of the prediction of progression. As more clinical evidence
      becomes available over time, these data can be added to the health economic
      model.

PMID- 22419453
TI  - Contrast aortography and the aortic annulus.

PMID- 22419455
TI  - Diagnosis of the performance of the state-specific multireference coupled-cluster
      method with different truncation schemes.
AB  - We have tested the linked version of a iterative (partial) triples correction for
      the Jeziorski-Monkhorst ansatz based state-specific multireference coupled
      cluster (SS-MRCC) approach with singles and doubles (SD) excitations [abbreviated
      as SS-MRCCSDT-1a and SS-MRCCSDT-1a+d]. The assessments of SS-MRCCSDT-1a and SS
      MRCCSDT-1a+d schemes have been performed on the ground potential energy surface
      (PES) of P4, Li(2),Be(2) systems which demand the MR description, and on study of
      the excitation energy between the ground and first excited state for P4 system.
      Illustrations in the isomerization of cyclobutadiene also show the power of the
      schemes. One of the designed features of the SS-MRCCSDT-n methods introduced here
      is that they do not require storage of the triples amplitudes. In the entire
      range of geometries, we found a definite improvement provided by SS-MRCC with SDT
      1a and SDT-1a+d schemes over the standard SD one. In the nondegenerate regions of
      PES, the closeness of the performance of the single-reference CC to the SS-MRCC
      methods increases after inclusion of even partial triple excitations. Generally,
      the performance of the SS-MRCCSDT-1a+d approach is closer to the corresponding
      full configuration interaction (FCI) one than to the SS-MRCCSDT-1a specially in
      the degenerate geometries (as is evident from nonparallelism error). The
      deviation from FCI for the first excited state of the P4 model using various SS
      MRCC theories with different truncation schemes obtained by converging on the
      second root of the effective Hamiltonian has also been reported. We also compare
      our results with the current generation state-of-the-art single and
      multireference CC calculations to envisage the usefulness of the present
      approach. Initial implementation indicates that the SS-MRCCSDT-n formalism can
      provide not only reliable excitation energies and barrier height even when used
      in a relatively small model space, but also offers a considerable promise in
      generating the entire energy surface with low nonparallelity error.

PMID- 22419454
TI  - High prevalence of anal human papillomavirus infection and associated risky
      behaviors in men infected with human immunodeficiency virus in Taiwan.
AB  - A cross-sectional study was conducted to investigate the prevalence, types, and
      risk factors associated with anal HPV infection among HIV-infected men in
      outpatient clinics at an AIDS designated hospital in Taiwan. Anal swabs were
      collect and PCR (polymerase chain reaction) was used to analyze the types of anal
      HPV infection. HPV DNA was detected in 74.2% of the 198 participants, including
      high-risk types (40.4%), low-risk types (18.2%) and multiple-types (6%). The most
      common types were HPV 16 (13.1%), 6 (10.4%), 11 (7.1%) and 18 (6.1%). The
      significant risk factor for being infected with any type or a high-risk type of
      HPV was having sexual partners (>3) in the preceding 6 months. Low-risk type of
      anal HPV infection was associated with a history of anal lesions. Our findings
      support the need for regular follow-up of all HIV/HPV coinfected patients and
      their partners to allow early detection of anal intraepithelial neoplasia.

PMID- 22419456
TI  - [Research frontiers and trends of the analytical technology for Chinese
      medicine].

PMID- 22419457
TI  - [Pharmacokinetics interaction among three major active compounds of Shengmai
      formula in rats].
AB  - OBJECTIVE: To investigate the pharmacokinetic interaction among three major
      bioactive compounds of Shengmai formula. METHODS: After oral administration of
      ginsenoside Rg(1), ginsenoside Rb(1) and schisandrin with the same dose(100
      mg.kg(-1)) individually or in combination, rat serum samples were extracted, then
      these three compounds were determined by liquid chromatography-mass
      spectrometry(LC-MS). The pharmacokinetic parameters of three compounds in single
      or combination form were calculated by WinNonLinu6.0 using non-compartment model.
      RESULTS: Compared with single drug group, the peak concentration of ginsenoside
      Rg(1) in combined group increased from(0.476 +/-0.238) MUg.ml(-1) to (1.946 +/
      1.432) MUg.ml(-1), AUC(0-infinity) increased from(0.523 +/-0.238) MUg.h.ml(-1) to
      (1.908 +/-1.319) MUg.h.ml(-1), CL decreased from(226311 +/- 96819) ml.h(-1).kg(
      1) to(90650 +/-73684) ml.h(-1).kg(-1) and Vd decreased from(317110 +/-154009)
      ml.kg(-1) to(130967 +/-78306) ml.kg(-1). While the pharmacokinetic parameters of
      ginsenoside Rb(1) and schisandrin showed no significant change. CONCLUSION:
      Combined oral administration of three compounds of Shengmai formula can improve
      the bioavailability of ginsenoside RgRg(1), however it does not change the
      pharmacokinetic behavior of ginsenoside RbRg(1) and schisandrin.

PMID- 22419458
TI  - [A new method for simultaneous assay of six organic acids in Lonicerae Japonicae
      Flos].
AB  - OBJECTIVE: To establish a method of quantitative analysis of multi-components by
      single marker(QAMS) for quality control of Lonicerae Japonicae Flos. METHODS: The
      contents of chlorogenic acid(CA) and caffeic acid(CfA) were determined, and the
      relative correction factors(RCF) of other organic acids were calculated, which
      were used for the indirect determination. RESULTS: The RCFs for the
      neochlorogenic acid(NCA), 3, 4-O-dicaffeoylquinic acid(3, 4-DCA), 3, 5-O
      dicaffeoylquinic acid(3, 5-DCA), and 4, 5-O-dicaffeoylquinic acid(4, 5-DCA) were
      5.462, 5.689, 2.313, 2.382(to CA) and 3.941, 4.103, 1.669, 1.718(to CfA),
      respectively. The established method was validated in different laboratories with
      different high performance liquid chromatography(HPLC) instruments and different
      chromatographic columns; the result indicated that the reproducibility was
      satisfactory. There was no significant difference between the established QAMS
      method and external reference method (P>0.05). CONCLUSION: The established QAMS
      method can be used for simultaneous determination of 6 organic acids as quality
      control of Lonicerae Japonicae Flos with easy available standard substances.

PMID- 22419459
TI  - [Determination of fifteen pesticide residues in Radix Paeoniae Alba by gas
      chromatography-mass spectrometry with large volume injection].
AB  - OBJECTIVE: To establish a method for the simultaneous determination of 15
      pesticides residues in Radix Paeoniae Alba by large volume injection-gas
      chromatography-mass spectrometry(LVI-GC-MS). METHODS: The pesticides, including
      organochlorine pesticides, organophosphorus pesticides and pyrethroid
      insecticides, were analyzed by LVI-GC-MS using DB-5MS capillary column (30 m X
      250 MUm, 0.25 MUm). The column temperature programming: initial temperature 40
      degree for 1 min, with the increasing rate of 20 degree/min to 210 degree for 2
      min, then with the increasing rate of 5 degree/min to 280 degree for 22 min. The
      flow of carrier gas was 1.0 ml/min with the injection volume of 15 MUl. RESULTS:
      The calibration curves of the pesticides were linear in the specified
      concentration ranges with correlation coefficients of 0.9937-0.9995. The average
      recoveries of the pesticides in Radix Paeoniae Alba spiked at two spiked levels
      ranged from 60.4 % to 106.8 % (for pendimethalin and 4, 4'-DDE those were 53.1 %
      and 45.2 %) with relative standard deviation(RSD) of 3.6 % to 18.6 % and the
      detection limits (S/N=3) were in the range of 0.16 MUg/kg to 3.59 MUg/kg.
      CONCLUSION: The established method for determination of multi-pesticide residue
      in Radix Paeoniae Alba is rapid, convenient and accurate with high sensitivity
      and low-cost.

PMID- 22419460
TI  - [Determination of nineteen organonitrogen pesticides in Paeoniae Radix Alba by
      capillary electrophoresis-mass spectrometry].
AB  - OBJECTIVE: To establish a capillary electrophoresis-mass spectrometry(CE-MS)
      method for the analysis of nineteen organonitrogen pesticides in Paeoniae Radix
      Alba. METHODS: CE-MS analysis was performed on a 70 cm X 50 MUm fused-silica
      capillary. The optimal buffer was composed of 1 % formic acid and 15 %
      methanol(V/V, pH 2.2). The temperature of capillary was controlled at 25 degree.
      The separation voltage was +20 kV. The optimal MS parameters were as follows: ESI
      MS analysis was performed in the positive mode; 90 % methanol containing 0.2 %
      formic acid with a flow rate of 8 MUl.min(-1) was selected as the sheath liquid;
      the flow rate and temperature of drying gas were 6 L.min(-1) and 250 degree,
      respectively; The nebulizing gas pressure was set at 5 psig; The optimal values
      of fragmentor and ESI voltage were 100 V and 5 000 V, respectively. RESULTS: The
      nineteen pesticides had good linearity over the testing ranges. The average
      recoveries were in the range of 80.1 %-108.4 % with RSDs less than 20 % (except
      ethoxyquin and spiroxamine, those of which were 29.2 % and 22.3 % at 0.01 mg.kg(
      1) concentration level). The LODs of nineteen pesticides were 0.503 ?10.1 MUg.kg(
      1). CONCLUSION: The method can be used effectively to analyze the nineteen
      organonitrogen pesticides residue in Paeoniae Radix Alba.

PMID- 22419461
TI  - [Identification of major components of traditional Chinese medicine Naodesheng
      tablet by HPLC-DAD-MS(n)].
AB  - OBJECTIVE: To identify the major components of traditional Chinese medicine
      Naodesheng tablet. METHODS: A HPLC-DAD-MS(n) based method was developed to
      analyze and identify the major components of Naodesheng tablet. Separation was
      performed on an Agilent Zorbax SB-C(18) column (4.6 mm X 250 mm, i.d, 5 MUm) with
      mobile phase consisting of water with 0.05 % formic acid and acetonitrile as
      gradient eluent at the flow rate of 0.5 ml.min(-1). RESULTS: A total of 43
      components were detected, among which 22 were identified by comparing their UV
      absorption profiles, the information of molecular Glucosyl puerarin weights, and
      structures provided by ESI-MS(n) with those of available standards and reference
      data, such as Safflor yellow A, 4'-O-Glucosyl puerarin, 3'-hydroxypuerarin,
      Genistein-8-C-apiosyl (1-6) glucoside, Puerarin, 6"-O-xylosyl puerarin, 6"-O
      apiosyl puerarin, 3'-methoxy puerarin, 3'-methoxy-6"-o-xylosyl puerarin, Daidzin,
      Genistin, Pueroside A, Notoginsenoside R(1), Ginsenoside Re, Ginsenoside
      Rg1,Daidzein,Biochanin A,Ginsenoside Rb(1), Ginsenoside Rc, Ginsenoside Rb(2),
      Ginsenoside Rb(3), Ginsenoside Rd. CONCLUSION: The proposed method can identify
      the main components of Naodesheng tablet and provide information for the quality
      control of this medicine.

PMID- 22419462
TI  - [Screening and identifying hepatotoxic components in Aucklandiae Radix with GC
      MS].
AB  - OBJECTIVE: To screen the potential hepatotoxic components in Chinese herb
      medicine Aucklandiae Radix. METHODS: The potential hepatotoxic components were
      screened using HepG2 cells labeled with fluorescein diacetate from 25 fractions
      of Aucklandiae Radix, in which the hepatotoxic compounds were further identified
      with GC-MS. RESULTS: Ten potential hepatotoxic fractions were screened. The
      identification results by GC-MS indicated that the main compounds in C09 were
      dehydrocostuslactone, santamarine (or magnolialide) and reynosin, and in C11 were
      alpha-costol and elemol. CONCLUSION: Dehydrocostuslactone, santamarine (or
      magnolialide), reynosin, alpha-costol and elemol are potential hepatotoxic
      compounds in Aucklandiae Radix.

PMID- 22419463
TI  - [Effects of kindling epilepsy and low frequency of epileptic focus on spontaneous
      neuropathic pain in rats].
AB  - OBJECTIVE: To investigate the effects of epileptogenesis and low frequency
      stimulation at epileptic focus on spontaneous neuropathic pain in rats. METHODS:
      Bipolar stimulating electrodes were implanted in the amygdala and current with
      constant intensity was applied to evoke kindling-induced seizures. In partial and
      generalized stages of seizure acquisition, neuroma model of spontaneous
      neuropathic pain was prepared by completely transection of the left sciatic and
      saphenous nerves of rats. Autotomy behavior was scored daily until d 63
      postoperatively. Rats were divided into 5 groups: Control (n=7), rats with
      partial seizures (1-3 stages, n=5), rats with generalized seizures (4-5 stages,
      n=7), rats with partial seizures and low frequency stimulation(n=4), rats with
      generalized seizures and low frequency stimulation(n=4). Low frequency
      stimulation was applied to the amygdala, the epileptic focus for 21 d from the d
      2 after nerve transection. RESULTS: Autotomy level in rats with partial seizures
      was significantly lower than that in controls. The autotomy scores during
      postoperative d 40 ?63 were significantly lower than those of controls, the area
      under the progression curve of autotomy behavior was decreased from 308.2 +/
      51.57 to 45.80 +/-24.64, the onset day of autotomy was postponed by 32 d and none
      of the animals with partial seizures showed high autotomy, while 71.4 % of
      controls showed that on d 63 postoperatively. Rats with generalized seizures
      showed autotomy similar to controls, except that the onset day was postponed by
      16 d. Autotomy behavior in rats receiving low frequency stimulation of the
      amygdala was not different from that in controls. CONCLUSION: Focal seizures can
      lower sensitivity to spontaneous neuropathic pain in rats, while low frequency
      stimulation applied to the focus can abolish such effect.

PMID- 22419464
TI  - [Effects of gestational isoflurane exposure on postnatal memory and learning in
      rats].
AB  - OBJECTIVE: To investigate the effects of gestational isoflurane exposure on
      postnatal memory and learning and growth-associated protein-43 (GAP-43),
      neuropeptide Y(NPY) expression in the hippocampus of pups. METHODS: Twelve
      maternal Sprague-Dawley rats at gestation d 18(E18) were randomly divided into
      isoflurane group (n=6) and control group (n=6). Rats in isoflurane group were
      exposed to 1.3 % isoflurane for 6 h. For control group, animals breathed in 30 %
      oxygen and air mixed gas at the same condition. Spatial learning and memory of
      the offspring were determined with the Morris Water Maze(MWM) after postnatal 4
      weeks. The changes of GAP-43 and NPY expression in the hippocampal CA1 region of
      the pups were determined by immunohistochemistry. RESULTS: In MWM training, the
      escape latency to platform of the pups in isoflurane group was significantly
      longer, and the time spent in the third quadrant and times of original platform
      crossing were less than those of control animals (P<0.05). The number and optical
      density of GAP-43 and NPY positive neurons in the hippocampus of pups decreased
      significantly in the isoflurane group compared with the controls (P <0.01).
      CONCLUSION: Isoflurane exposure in pregnant rats significantly impairs the
      spatial memory and learning of their pups at a juvenile age, which may be
      associated with the down-regulation of GAP-43 and NPY in the hippocampus.

PMID- 22419465
TI  - [Effects of sea cucumber cerebroside and its long-chain base on lipid and glucose
      metabolism in obese mice].
AB  - OBJECTIVE: To investigate the effect of sea cucumber cerebroside(SCC) and its
      long-chain base(LCB) on lipid and glucose metabolism in obese mice. METHODS: The
      mouse obese model was established by feeding high fat diet. The mice were
      randomly assigned to 4 groups: control group, model group, SCC group and LCB
      group. After 4 weeks, the glucose tolerance test was undertaken. After 5 weeks,
      the body fat content, organic indexes, serum lipid level, glycemic index and
      liver lipid level were determined. RESULTS: Compared with the model group, the
      glucose tolerance in the SCC group and LCB group was ameliorated significantly
      (P<0.01, P<0.05); glycemic index (P<0.01, P<0.01), the weight of adipose tissue
      (P<0.05, P<0.01) and the hepatic TG were reduced significantly (P<0.05, P<0.05).
      CONCLUSION: Sea cucumber cerebroside and its long-chain base can improve the
      glucose and lipid metabolism in obese mice.

PMID- 22419466
TI  - [Effects of stellate ganglion block on blood pressure in spontaneously
      hypertensive rats].
AB  - OBJECTIVE: To investigate the effects of stellate ganglion block (SGB) on blood
      pressure in spontaneously hypertensive rats(SHRs). METHODS: Thirty-two 10-week
      old male spontaneously hypertensive rats(SHRs) were assigned randomly into four
      groups: left stellate ganglion block group(Group LS), right stellate ganglion
      block group(Group RS), captopril group(Group D) and control group(Group C).
      Arterial systolic blood pressure(SBP) was measured, and endothelin (ET-1) and
      endothelial nitric oxide synthase(eNOS) in blood vessels were detected by
      radioimmunoassay. RESULTS: Compared with baseline value, the blood pressure of
      Group LS gradually increased significantly (P<0.05 or P <0.01); however, the
      blood pressure of Group RS was stable(P >0.05) and increased only at week 2(P
      <0.05).The blood pressure of Group D decreased significantly at week 2 and week
      4, and it remained stable compared with baseline value (P<0.05). The blood
      pressure of Group C gradually increased at weeks 2-10, compared with baseline
      values (P <0.01). Compared with Group LS and Group C, the expression of eNOS in
      blood vessels of Group RS significantly increased (P <0.05), and ET-1 decreased
      (P <0.05). CONCLUSION: The right stellate ganglion block can significantly lower
      blood pressure, down-regulate ET-1 and up-regulate eNOS protein expression.

PMID- 22419467
TI  - [Expression pattern of hoxd3 gene during early development of wild-type zebrafish
      embryos].
AB  - OBJECTIVE: To investigate the expression pattern of hoxd3 gene during early
      embryogenesis and angiogenesis of wild-type zebrafish. METHODS: Total RNA was
      extracted from embryos of zebrafish in different development stages by trizol.
      The cDNA of hoxd3 gene was amplified by RT-PCR. The RT-PCR product was ligated to
      pCS(2+) vector by T4 DNA ligatase polymerase and sequenced. T3 RNA polymerase in
      vitro transcription system was used to obtain the probe of digoxin-labeled anti
      sense mRNA of hoxd3 gene. The expression pattern of hoxd3 was detected by whole
      embryo in situ hybridization (WISH) with anti-sense mRNA probe. RESULTS: pCS(2+)
      hoxd3 plasmid was successfully constructed, which was used to prepare anti-sense
      mRNA probe of hoxd3 in vitro. Expression pattern of hoxd3 gene was detected by
      WISH during zebrafish early embryogenesis and angiogenesis. It was observed that
      hoxd3 mRNA was expressed at the junction region of midbrain and hindbrain in wild
      type zebrafish in embryos at 24 ?72h postfertilization(hpf). CONCLUSION: hoxd3
      gene is mainly expressed in nervous system of wide-type zebrafish embryos.

PMID- 22419468
TI  - [Screening of differentially expressed microRNAs in bone marrow-derived
      mesenchymal stem cells during osteoporosis and their function in stem cell
      differentiation].
AB  - OBJECTIVE: To screen differentially expressed microRNAs in bone marrow-derived
      mesenchymal stem cells (BMMSCs) during osteoporosis and their function in stem
      cell differentiation. METHODS: The osteoporosis model was induced by ovariectomy
      in mice.The differentially expressed microRNAs in BMMSCs during osteoporosis were
      screened with microRNA microarray chip and their expressions during osteogenesis
      and adipogenesis were detected by RT-PCR. RESULTS: Ten differentially expressed
      microRNAs were detected in BMMSC during osteoporosis. The expression of 5
      specific microRNAs altered significantly during osteogenic differentiation and 3
      microRNAs altered during adipogenic differentiation. CONCLUSION: A serials of
      differentially expressed microRNAs may be involved in functional defects of BMMSC
      during osteoporosis.

PMID- 22419469
TI  - [Construction of miRNA expression vector dual-targeting on HIF-1alpha/survivin
      genes and its effects on proliferation of pancreatic cancer Panc-1 cell line].
AB  - OBJECTIVE: To design and construct miRNA expression vector dual-targeting on HIF
      1alpha and survivin genes and to investigate its effects on proliferation of
      human pancreatic cancer cells. METHODS: The specific pre-miRNA single strand DNA
      oligos for HIF-1 alpha and survivin genes were designed and synthesized, then via
      annealing and ligating with pcDNA6.2-GW/EmGFP-miR plasmids in order, two kinds
      (eight in total) of miRNA expression vectors for HIF-1alpha and survivin genes
      were constructed. The vectors, which were most effective to knockdown target
      genes, were screened with real-time RT-PCR and combined by chaining technology to
      construct dual-targeting plasmid. The recombined dual-targeting plasmid, mono
      targeting plasmids and negative plasmid were transfected into Panc-1 cells, the
      suppression effect on two genes was identified by real-time RT-PCR, Western blot
      and MTT assays. RESULTS: The miRNA expression plasmids anti-H, anti-S and anti
      H+S were successfully constructed by identification of sequencing analysis, and
      they were able to effectively inhibit the target genes expressing. MTT assays
      showed that the inhibition effect of dual-targeting vector anti-H+S was higher
      than that of mono-targeting vectors anti-H and anti-S 72 h after transfection
      (P<0.05). CONCLUSION: The effective miRNA expression vector dual-targeting on HIF
      1alpha and survivin genes has been successfully constructed. The inhibition
      effect on proliferation of pancreatic cancer Panc-1 cells by dual-targeting
      plasmid was higher than that by mono-target plasmids.

PMID- 22419470
TI  - [Association of Helicobacter pylori infection and serum homocysteine level in
      patients with cerebral infarction].
AB  - OBJECTIVE: To investigate the association of Helicobacter pylori infection and
      serum homocysteine(Hcy) levels with acute cerebral infarction. METHODS: Serum Hp
      IgG, Hp-CagA-IgG and Hcy were detected by biological micro-array analysis system
      in 85 patients with acute cerebral infarction and 40 healthy subjects (control
      group). RESULTS: The positive rates of Hp-IgG and Hp-CagA-IgG significantly
      increased in cerebral infarction group compared with controls (P<0.05). There
      were significant differences in serum Hcy level between Hp-CagA-IgG positive and
      negative patients (P<0.05), but not between Hp-IgG positive and negative patients
      (P>0.05). CONCLUSION: CagA-positive Hp infection may increase the risk of
      cerebral infarction, which might be associated with the increased serum
      homocysteine level.

PMID- 22419471
TI  - [Early management of intracranial ruptured vertebral dissecting aneurysms].
AB  - OBJECTIVE: To evaluate the early management of intracranial ruptured vertebral
      dissecting aneurysms. METHODS: Twenty-two patients with ruptured vertebral
      dissecting aneurysms were managed by various treatment modalities according to
      their conditions. One aneurysm was treated by proximal vertebral artery coiling,
      15 aneurysms by aneurysm and parent artery coiling, and 5 aneurysms by stent
      assisted coiling (4 of 5 by stent-within-a-stent technique), one by single double
      stent. Bloody cerebrospinal fluid was drained by postoperative lumbar
      subarachnoid drainage in order to prevent cerebral vasospasm. RESULTS: All 22
      cases were successful without bleeding complication during the operation.There
      was 1 case of early postoperative non-aneurysmal hemorrhage, 2 cases of posterial
      group cranial nerves palsies, 1 case harbored Hunt & Hess IV who gave up
      treatment. After follow-up for 3-18 months, there was no rebleeding and
      infarction. Twenty patients recovered well, except 1 having posterial group
      cranial nerves palsies. Fourteen cases were followed up by angiography. In 3
      patients treated by stent-assisted coiling, DSA showed that aneurysms disappeared
      and loading vessel passed freely.DSA of 11 cases with aneurysm and parent artery
      coiling demonstrated complete obliteration of the dissection without aneurysm
      imaging. CONCLUSION: Early endovascular treatment of ruptured vertebral
      dissecting aneurysms is essential. The selective method of endovascular
      management according to the characteristics of aneurysm is safe and effective.
      Double stent-assisted coiling should be the first choice.

PMID- 22419472
TI  - [Double balloon endoscopy in diagnosis of patients with obscure gastrointestinal
      bleeding].
AB  - OBJECTIVE: To assess the diagnostic value of double balloon endoscopy (DBE) for
      obscure gastrointestinal bleeding (OGIB) METHODS: The data of 103 OGIB patients
      who underwent DBE from January 2007 to September 2010 in the First Affiliated
      Hospital, Zhejiang University School of Medicine were retrospectively analyzed.
      RESULTS: DBE was successfully performed in all 103 patients without
      complications. Of 103 patients, 66(64.1 %) had positive DBE findings and 28 had
      surgery procedures(27.2 %). Ninety-four patients finally acquired positive
      diagnosis, including small intestine tumor(31.1 %), angiodysplasia(22.3 %),
      exulceratio simplex(9.7 %), Crohn's disease(6.8 %), diverticulum(4.9 %),
      abdominal purpure(4.9 %), etc. Lesions occurred more frequently in proximal small
      intestine than in distal small intestine (56.3 % Compared with 30.1 %, P<0.001).
      CONCLUSION: DBE is a safe, effective and reliable procedure for the diagnosis of
      OGIB.

PMID- 22419473
TI  - [Roles of microvesicles in tumor progress and its clinical application].
AB  - Microvesicles transport special proteins, micro RNA and DNA segments, which
      provides new access to intercellular communication. Tumor-derived membrane
      microvesicles (TMV) are involved in the tumor progress by transporting tumor
      derived proteins, delivering microRNA to surrounding normal cells to alter their
      phenotype and promoting reverse transcription to interfere gene stability and to
      create tumor microenvironment. TMV also play crucial roles in tumor angiogenesis
      and matrix degradation, which facilitates malignant cell metastasis. TMVs are
      also involved in escaping immunological surveillance by intensifying the function
      of suppressor T cell and inducing apoptosis of cytotoxic T cells. On the other
      hand, microvesicles carry tumor antigens and can be used for development of tumor
      vaccines; some new vaccines such as AEX and DEX are under early clinical trials.
      Circulating microRNA and DNA segments in body fluid can be a new potential
      biomarker for cancer diagnosis and prognosis. Purification of microvesicles needs
      to be further improved, which is important for identification of microvesicles
      and their subtypes.

PMID- 22419474
TI  - [Research progress on MKP-1 in tumor drug resistance].
AB  - The main obstacle for chemotherapy is tumor drug resistance. Studying the
      mechanisms of drug resistance and reversing drug resistance is the key to improve
      the effectiveness of chemotherapy. It has been reported that MKP-1 plays an
      important role in tumor drug resistance. MKP-1, as a negative regulator of MAPKs,
      is involved in the MAPKs mediated drug resistance and is regulated by ERK and p38
      signaling pathways.However, the relationship between MKP-1 and other drug
      resistance-related signaling pathways is not clear and requires further
      investigation.

PMID- 22419475
TI  - [Research progress on olfactory receptor].
AB  - The olfactory perception is the process that the olfactory receptor is activated
      by odorous molecules, which induce the transduction of signal in the cell and the
      chemical information is transduced into electrical impulses. After the changed
      signal is transmitted to the brain, the whole perception process completes. OR
      gene belongs to the multigene family. The coded olfactory receptor proteins
      belong to the G-protein-coupled receptor (GPCR) superfamily and therefore are
      invariably seven-transmembrane domain(7TM) protein. Olfactory receptor protein
      plays an important role in olfactory perception and signal transduction process.

PMID- 22419476
TI  - Analysis of 11-nor-Delta9 -tetrahydrocannabinol-9-carboxylic acid and its
      glucuronide in urine by capillary electrophoresis/mass spectrometry.
AB  - Delta(9) -Tetrahydrocannabinol is the primary psychoactive component in cannabis,
      one of the most commonly used illicit drugs in the world. This paper describes a
      simple and rapid method for direct analysis of major metabolites of Delta(9) 
      tetrahydrocannabinol; 11-nor-Delta(9) -tetrahydrocannabinol-9-carboxylic acid and
      its glucuronide in urine by capillary electrophoresis/mass spectrometry. The only
      pretreatment needed for a urine sample was dilution with methanol containing an
      internal standard and centrifugation. Electrophoresis was carried out in an
      untreated fused-silica capillary (50 um i.d. * 85 cm) filled with 40 m m ammonium
      formate (pH 6.4). An analysis could be completed within 10 min. For both
      compounds, the assay was linear over the range 0.1-10 ug/mL in urine with
      correlation coefficients (r(2) ) >0.99 and the limit of detection was 0.5 pg (10
      nL injection). The detection yields and reproducibilities were determined at
      three different concentrations (0.1, 0.5 and 2 ug/mL in urine). The mean
      detection yields were 60-99%. The intra- and inter-day relative standard
      deviations of migration times were 0.063-0.19 and 0.18-0.36%, and those of peak
      areas were 4.2-18 and 5.9-25%, respectively. The proposed method successfully
      analyzed the urine samples of cannabis users.

PMID- 22419477
TI  - Synthesis of dendritic platinum nanoparticles/lucigenin/reduced graphene oxide
      hybrid with chemiluminescence activity.
AB  - Multifunctional hybrid: A dendritic platinum nanoparticle/lucigenin/reduced
      graphene oxide (RGO) hybrid with chemiluminescence (CL) activity was prepared for
      the first time by using lucigenin as a linker through simultaneous reduction of
      H(2) PtCl(4) and a lucigenin-functionalized graphene oxide composite by sodium
      borohydride (see scheme). The hybrid may have potential applications as a CL
      sensor, in catalysis, energy conversion, and opto-electronic systems.

PMID- 22419479
TI  - Comparative analyses of regulatory T cell subsets in patients with hepatocellular
      carcinoma: a crucial role of CD25(-) FOXP3(-) T cells.
AB  - Regulatory T cells (Tregs) play pivotal role in cancer-induced immunoediting.
      Increment of CD25(high+) FOXP3+ natural Tregs has been reported in patients with
      hepatocellular carcinoma (HCC); however, the involvement of other type of Tregs
      remain elusive. We aimed to clarify whether FOXP3- Tregs are increased and
      functionally suppressive or not in patients with HCC. We enrolled 184 hepatitis C
      infected patients with chronic liver diseases or HCC, 57 healthy subjects and 27
      HCC patients with other etiology. Distinct Treg subsets were phenotypically
      identified by the expression of CD4, CD25, CD127 and forkhead/winged helix
      transcription factor (FOXP3). Their gene profiles, frequency and suppressor
      functions against T cell proliferation were compared among the subjects. To
      examine the molecules involving in Treg differentiation, we cultured naive CD4+ T
      cells in the presence of HCC cells and dendritic cells. We determined two types
      of CD4+ CD127- T cells with comparable regulatory ability; one is CD25(high+)
      cells expressing FOXP3 (CD25(high+) FOXP3+ Tregs) and the other is CD25- cells
      without FOXP3- expression (CD25- FOXP3- cells). The peripheral or intrahepatic
      frequency of CD25- FOXP3- Tregs in HCC patients is higher than those in other
      groups, of which significance is more than CD25(high+) FOXP3+ cells. Of
      importance, CD25- FOXP3- Tregs, but not CD25(high+) FOXP3+ cells, dynamically
      change in patients accompanied by the ablation or the recurrence of HCC. CD25-
      FOXP3- T cells with CD127- IL-10+ phenoype are inducible in vitro from naive
      CD4(+) T cells, in which programmed cell death 1 ligand 1, immunoglobulin-like
      transcript 4 and human leukocyte antigen G are involved.. In conclusion, CD25-
      FOXP3- Tregs with suppressive capacity are increased in patients with HCC,
      suggesting their distinct roles from CD25+ FOXP3+ Tregs.

PMID- 22419480
TI  - Vector activity and propagule size affect dispersal potential by vertebrates.
AB  - Many small organisms in various life stages can be transported in the digestive
      system of larger vertebrates, a process known as endozoochory. Potential
      dispersal distances of these "propagules" are generally calculated after
      monitoring retrieval in experiments with resting vector animals. We argue that
      vectors in natural situations will be actively moving during effective transport
      rather than resting. We here test for the first time how physical activity of a
      vector animal might affect its dispersal efficiency. We compared digestive
      characteristics between swimming, wading (i.e. resting in water) and isolation
      (i.e. resting in a cage) mallards (Anas platyrhynchos). We fed plastic markers
      and aquatic gastropods, and monitored retrieval and survival of these propagules
      in the droppings over 24 h. Over a period of 5 h of swimming, mallards excreted
      1.5 times more markers than when wading and 2.3 times more markers than isolation
      birds, the pattern being reversed over the subsequent period of monitoring where
      all birds were resting. Retention times of markers were shortened for
      approximately 1 h for swimming, and 0.5 h for wading birds. Shorter retention
      times imply higher survival of propagules at increased vector activity. However,
      digestive intensity measured directly by retrieval of snail shells was not a
      straightforward function of level of activity. Increased marker size had a
      negative effect on discharge rate. Our experiment indicates that previous
      estimates of propagule dispersal distances based on resting animals are
      overestimated, while propagule survival seems underestimated. These findings have
      implications for the dispersal of invasive species, meta-population structures
      and long distance colonization events.

PMID- 22419478
TI  - Phonological processing in first-degree relatives of individuals with autism: an
      fMRI study.
AB  - Autism spectrum disorders (ASD) are complex neurodevelopmental disorders. Twin
      studies have provided heritability estimates as high as 90% for idiopathic ASD.
      Further evidence for the spectrum's heritability is provided by the presence of
      the broad autism phenotype (BAP) in unaffected first-degree relatives. Language
      ability, specifically phonological processing, is proposed to be a core BAP
      trait. To date, however, no functional neuroimaging investigations of
      phonological processing in relatives of individuals with ASD have been
      undertaken. We conducted a functional magnetic resonance imaging (fMRI) study in
      parents of children with ASD utilizing a priming task probing implicit
      phonological processing. In our condition that placed heavier demands on
      phonological recoding, parents exhibited greater hemodynamic responses than
      controls in a network of cortical regions involved in phonological processing.
      Across conditions, parents exhibited enhanced priming-induced response
      suppression suggesting compensatory neural processing. A nonword repetition test
      used in previous studies of relatives was also administered. Correlations between
      this measure and our functional measures also suggested compensatory processing
      in parents. Regions exhibiting atypical responses in parents included regions
      previously implicated in the spectrum's language impairments and found to exhibit
      structural abnormalities in a parent study. These results suggest a possible
      neurobiological substrate of the phonological deficits proposed to be a core BAP
      trait. However, these results should be considered preliminary. No previous fMRI
      study has investigated phonological processing in ASD, so replication is
      required. Furthermore, interpretation of our fMRI results is limited by the fact
      that the parent group failed to exhibit behavioral evidence of phonological
      impairments.

PMID- 22419481
TI  - Differential effectiveness of novel and old legume-rhizobia mutualisms:
      implications for invasion by exotic legumes.
AB  - The degree of specialization in the legume-rhizobium mutualism and the variation
      in the response to different potential symbionts are crucial factors for
      understanding the process of invasion by exotic legumes and the consequences for
      the native resident plants and bacteria. The enhanced novel mutualism hypothesis
      predicts that exotic invasive legumes would take advantage of native rhizobia
      present in the invaded soils. However, recent studies have shown that exotic
      legumes might become invasive by using exotic introduced microsymbionts, and that
      they could be a source of exotic bacteria for native legumes. To unravel the role
      of novel and old symbioses in the progress of invasion, nodulation and symbiotic
      effectiveness were analyzed for exotic invasive plants and native co-occurring
      legumes in a Mediterranean coastal dune ecosystem. Although most of the studied
      species nodulated with bacteria from distant origins these novel mutualisms were
      less effective in terms of nodulation, nitrogenase activity and plant growth than
      the interactions of plants and bacteria from the same origin. The relative effect
      of exotic bradyrhizobia was strongly positive for exotic invasive legumes and
      detrimental for native shrubs. We conclude that (1) the studied invasive legumes
      do not rely on novel mutualisms but rather need the co-introduction of compatible
      symbionts, and (2) since exotic rhizobia colonize native legumes in invaded
      areas, the lack of effectiveness of these novel symbiosis demonstrated here
      suggests that invasion can disrupt native belowground mutualisms and reduce
      native legumes fitness.

PMID- 22419482
TI  - Placement of the diaphragmatic vertebra in catarrhines: implications for the
      evolution of dorsostability in hominoids and bipedalism in hominins.
AB  - A fundamental adaptation to orthograde posture and locomotion amongst living
      hominoid primates is a numerically reduced lumbar column, which acts to stiffen
      the lower back and reduce injuries to the intervertebral discs. A related and
      functionally complementary strategy of spinal stability is a caudal position of
      the diaphragmatic vertebra relative to the primitive condition found in
      nonhominoid primates and most other mammals. The diaphragmatic vertebra marks the
      transition in vertebral articular facet (zygapophysis) orientation, which either
      resists (prediaphragmatic) or allows (postdiaphragmatic) trunk movement in the
      sagittal plane (i.e., flexion and extension). Unlike most mammals, which have
      dorsomobile spines (long lumbar columns and cranially placed diaphragmatic
      vertebrae) for running and leaping, hominoids possess dorsostable spines (short
      lumbar columns and caudally placed diaphragmatic vertebrae) adapted to orthogrady
      and antipronogrady. In contrast to humans and other extant hominoids, all known
      early hominin partial vertebral columns demonstrate cranial displacement of the
      diaphragmatic vertebra. To address this difference, variation in diaphragmatic
      placement is assessed in a large sample of catarrhine primates. I show that while
      hominoids are characterized by modal common placement of diaphragmatic and last
      rib-bearing vertebrae in general, interspecific differences in intraspecific
      patterns of variation exist. In particular, humans and chimpanzees show nearly
      identical patterns of diaphragmatic placement. A scenario of hominin evolution is
      proposed in which early hominins evolved cranial displacement from the ancestral
      hominid condition of common placement to achieve effective lumbar lordosis during
      the evolution of bipedal locomotion.

PMID- 22419483
TI  - Two novel patients with Bohring-Opitz syndrome caused by de novo ASXL1 mutations.
AB  - Bohring-Opitz syndrome (BOS) is a rare condition characterized by facial
      anomalies, multiple malformations, failure to thrive and severe intellectual
      disabilities. Recently, the cause was identified on the basis of de novo
      heterozygous mutations in the ASXL1 gene. We report on two novel cases carrying
      two previously undescribed mutations (c.2407_2411del5 [p.Q803TfsX17] and
      c.2893C>T [p.R965X]). These new data further support ASXL1 as cause of BOS and
      may contribute to a more precise definition of the phenotype caused by the
      disruption of this gene.

PMID- 22419484
TI  - A taxonomist's view on genomic authentication.
AB  - A brief history of taxonomy, for the most part plant oriented, is provided, which
      demonstrates the use of morphology early on, through the stages when different
      technologies became available at different times until the present use of genomic
      tools. Genomic authentication facilitates with greater precision than ever before
      the identification of an organism or part thereof. In this chapter I made an
      attempt to stress that, in general, but more so for genomic authentication, the
      use of the variation inherent in taxa down to the lowest level of the hierarchy
      of classification needs to be used to achieve a high degree of correct
      authentication.

PMID- 22419485
TI  - DNA fingerprinting, DNA barcoding, and next generation sequencing technology in
      plants.
AB  - DNA fingerprinting of plants has become an invaluable tool in forensic,
      scientific, and industrial laboratories all over the world. PCR has become part
      of virtually every variation of the plethora of approaches used for DNA
      fingerprinting today. DNA sequencing is increasingly used either in combination
      with or as a replacement for traditional DNA fingerprinting techniques. A prime
      example is the use of short, standardized regions of the genome as taxon barcodes
      for biological identification of plants. Rapid advances in "next generation
      sequencing" (NGS) technology are driving down the cost of sequencing and bringing
      large-scale sequencing projects into the reach of individual investigators. We
      present an overview of recent publications that demonstrate the use of "NGS"
      technology for DNA fingerprinting and DNA barcoding applications.

PMID- 22419486
TI  - Challenges in the DNA barcoding of plant material.
AB  - DNA barcoding, using a short gene sequence from a standardized region of the
      genome, is a species identification tool which would not only aid species
      discovery but would also have applications ranging from large-scale biodiversity
      surveys through to identification of a single fragment of material in forensic
      contexts. To fulfill this vision a universal, relatively cheap, scalable system
      needs to be in place. The mitochondrial locus being used for many animal groups
      and algae is not suitable for use in land plants, and an appropriate alternative
      is needed.Progress has been made in the selection of two alternative regions for
      plant DNA barcoding. There are however many challenges in finding a solution that
      fulfills all the requirements of a successful, universally applicable barcode,
      and in the short term a pragmatic solution that achieves as much as possible and
      has payoffs in most areas has been chosen. Research continues in areas ranging
      from the technicalities of sequencing the regions to data analysis and the
      potential improvements that may result from the developing technology and data
      analysis systems.The ultimate success of DNA barcoding as a plant identification
      tool for all occasions depends on the building of a reference database and it
      fulfilling the requirements of potential users such that they are able to achieve
      valid results through its use, that would be more time consuming and costly, and
      less reliable using other techniques.

PMID- 22419487
TI  - Plant genetics for forensic applications.
AB  - An emerging application for plant DNA fingerprinting and barcoding involves
      forensic investigations. Examples of DNA analysis of botanical evidence include
      crime scene analysis, identifying the source of commercial plant products, and
      investigation of trade in illicit drugs. Here, we review real and potential
      applications of DNA-based forensic botany and provide a protocol for
      microsatellite genotyping of leaf material, a protocol that could be used to link
      a suspect to a victim or to a crime scene.

PMID- 22419488
TI  - DNA purification from multiple sources in plant research with homemade silica
      resins.
AB  - DNA purification is a routine procedure in most plant laboratories. Although
      different kits are available in the market allowing convenient DNA purification,
      the cumulative cost of purchasing multiple kits for a laboratory can be
      staggering. Here, we describe a protocol using homemade silicon dioxide matrix
      for DNA purification from Escherichia coli and Agrobacterium tumefaciens cells,
      PCR and restriction digestion mixtures, agarose gel slices and plant tissues.
      Compared with the commercial kits, this protocol enables easy DNA purification
      from diverse sources with comparable yield and purity at negligible expenses.

PMID- 22419489
TI  - Random amplified marker technique for plants rich in polyphenols.
AB  - More than 10,000 publications using the random amplified polymorphic DNA (RAPD)
      or related arbitrary marker techniques have been published in two decades of its
      inception in 1990. Despite extensive use, RAPD technique has also attracted some
      criticisms, mainly for lack of reproducibility. In the light of its widespread
      applications, the objective of this chapter is to (1) provide a protocol for RAPD
      assay, (2) identify the potential factors affecting the optimization of the RAPD
      assays, and (3) provide proper statistical analysis to avoid false positives. It
      is suggested that after proper optimization, the RAPD is a reliable, sensitive,
      and reproducible assay having the potential to detect a wide range of DNA
      variations. Analyses of the relevant fragments generated in RAPD profile allow
      not only to identify some of the molecular events implicated in the genomic
      instability but also to discover genes playing key roles in genetic evolution and
      gene mapping. RAPD markers will continue to be boon for genetic studies of those
      organisms where yet no sequence information or scanty information is available.

PMID- 22419490
TI  - Amplified fragment length polymorphism: an invaluable fingerprinting technique
      for genomic, transcriptomic, and epigenetic studies.
AB  - Amplified fragment length polymorphism (AFLP) is a PCR-based technique that uses
      selective amplification of a subset of digested DNA fragments to generate and
      compare unique fingerprints for genomes of interest. The power of this method
      relies mainly in that it does not require prior information regarding the
      targeted genome, as well as in its high reproducibility and sensitivity for
      detecting polymorphism at the level of DNA sequence. Widely used for plant and
      microbial studies, AFLP is employed for a variety of applications, such as to
      assess genetic diversity within species or among closely related species, to
      infer population-level phylogenies and biogeographic patterns, to generate
      genetic maps, and to determine relatedness among cultivars. Variations of
      standard AFLP methodology have been also developed for targeting additional
      levels of diversity, such as transcriptomic variation and DNA methylation
      polymorphism.

PMID- 22419491
TI  - Restriction fragment length polymorphism of the 5S-rRNA-NTS region: a rapid and
      precise method for plant identification.
AB  - Molecular genetic methods have several advantages over classical morphological
      and chemical analyses. The genetic method requires genotype instead than
      phenotype, therefore PCR-based techniques have been widely used for a rapid
      identification of plant species, varieties and chemotypes. Recently, the
      molecular discrimination of some higher plant species has been evaluated using
      sequences of a 5S-rRNA gene spacer region. The variation in the nontranscribed
      sequence (NTS) region has been used in a number of plant species for studying
      intraspecific variation, genome evolution, and phylogenetic reconstruction. Here,
      we describe a rapid method based on the use of the 5S-rRNA-NTS region as a tool
      for plant DNA fingerprinting, which combines PCR, sequencing and restriction
      fragment length polymorphism analyses.

PMID- 22419492
TI  - ISSR: a reliable and cost-effective technique for detection of DNA polymorphism.
AB  - With the emergence of more and more molecular markers as useful tools in plethora
      of population genetic and phylogenetic studies, choice of marker system for a
      particular study has become mind boggling. These marker systems differ in their
      advantages and disadvantages, so it is imperative to keep in mind all the pros
      and cons of the technique while selecting one for the problem to be
      addressed.Here, we have shed light on the ISSR (intersimple sequence repeat)
      technique, as a marker of choice if one wants to go for properties such as
      reliability, simplicity, cost effectiveness, and speed, in addition to assessing
      genetic diversity between closely related individuals. We have outlined here the
      whole methodology of this technique with an example of Tribulus terrestris as
      case study.

PMID- 22419493
TI  - Development of sequence characterized amplified region from random amplified
      polymorphic DNA amplicons.
AB  - Among the PCR-based markers that are most widely used in molecular genetic
      studies, SCARs (sequence characterized amplified regions) have the advantage of
      being less sensitive to the conditions of a standard PCR due to its primer size
      when compared to RAPD (random amplified polymorphic DNA) and hence are more
      specific and reproducible. Moreover, SCARs require no radioactive isotopes and
      detect only a single locus. Here, we describe the development of SCAR from RAPD
      amplicons.

PMID- 22419494
TI  - Authentication of medicinal plants by SNP-based multiplex PCR.
AB  - Highly variable intergenic spacer and intron regions from nuclear and cytoplasmic
      DNA have been used for species identification. Noncoding internal transcribed
      spacers (ITSs) located in 18S-5.8S-26S, and 5S ribosomal RNA genes (rDNAs)
      represent suitable region for medicinal plant authentication. Noncoding regions
      from two cytoplasmic DNA, chloroplast DNA (trnT-F intergenic spacer region), and
      mitochondrial DNA (fourth intron region of nad7 gene) are also successfully
      applied for the proper identification of medicinal plants. Single-nucleotide
      polymorphism (SNP) sites obtained from the amplification of intergenic spacer and
      intron regions are properly utilized for the verification of medicinal plants in
      species level using multiplex PCR. Multiplex PCR as a variant of PCR technique
      used to amplify more than two loci simultaneously.

PMID- 22419495
TI  - Multiplex PCR method to discriminate Artemisia iwayomogi from other Artemisia
      plants.
AB  - Some plants in the genus Artemisia have been used for medicinal purposes. Among
      them, Artemisia iwayomogi, commonly referred to as "Haninjin," is one of the
      major medicinal materials used in traditional Korean medicine. By contrast,
      Artemisia capillaris and both Artemisia argyi and Artemisia princeps, referred to
      as "Injinho" and "Aeyup," respectively, are used to treat diseases different from
      those for which "Haninjin" is prescribed. Therefore, the development of a
      reliable method to differentiate each Artemisia herb is necessary. We found that
      a random amplified polymorphic DNA (RAPD) method can be used to efficiently
      discriminate a few Artemisia plants from one another. To improve the reliability
      of RAPD amplification, we designed primer sets based on the nucleotide sequences
      of RAPD products to amplify a sequence-characterized amplified region (SCAR)
      marker of A. iwayomogi. In addition, we designed two other primer sets to amplify
      SCAR markers of "Aeyup" (A. argyi and A. princeps) along with "Injinho" (A.
      capillaris) and Artemisia japonica, which are also traded in Korean herbal
      markets. Using these three primer sets, we developed a multiplex PCR method
      concurrently not only to discriminate A. iwayomogi from other Artemisia plants,
      but also to identify Artemisia plants using a single PCR process.

PMID- 22419496
TI  - Loop-mediated isothermal amplification for the detection of plant pathogens.
AB  - Loop-mediated isothermal amplification (LAMP) is a technique involving the use of
      four to six primers (two inner primers, two outer primers, and two loop primers)
      and the strand displacement activity of Bacillus subtilis-derived (Bst) DNA
      polymerase. The end result of strand displacement and loop formation and
      synthesis is the single-temperature amplification of a highly specific fragment
      from a DNA template at a much greater titre than that obtained with polymerase
      chain reaction. With LAMP, there are several methods to determine a positive
      reaction. Presented here are three alternative methods: gel electrophoresis,
      hydroxynaphthol blue colorimetric dye, and the fluorescent intercalating
      PicoGreen((r)) reagent.

PMID- 22419497
TI  - Genomic DNA extraction and barcoding of endophytic fungi.
AB  - Endophytes live inter- and/or intracellularly inside healthy aboveground tissues
      of plants without causing disease. Endophytic fungi are found in virtually every
      vascular plant species examined. The origins of this symbiotic relationship
      between endophytes go back to the emergence of vascular plants. Endophytic fungi
      receive nutrition and protection from their hosts while the plants benefit from
      the production of fungal secondary metabolites, which enhance the host plants'
      resistance to herbivores, pathogens, and various abiotic stresses. Endophytic
      fungi have attracted increased interest as potential sources of secondary
      metabolites with agricultural, industrial, and medicinal use. This chapter
      provides detailed protocols for isolation of genomic DNA from fungal endophytes
      and its use in polymerase chain reaction-based amplification of the internal
      transcribed spacer region between the conserved flanking regions of the small and
      large subunit of ribosomal RNA for barcoding purposes.

PMID- 22419498
TI  - Using GenBank(r) for genomic authentication: a tutorial.
AB  - The GenBank((r)) database is perhaps one of the most important repositories of
      genetic information. A researcher working in the field of genomic authentication
      must therefore be equipped with the skills needed to competently access the
      required information from this database whilst ultimately contributing their own
      data to it. This chapter presents a practical guide to using GenBank((r)) to
      search for sequences, search and align unknown sequences using BLAST, and
      uploading and maintaining your own sequences. This chapter also details some
      other software helpful in sequence manipulation.

PMID- 22419499
TI  - Direct investigation of covalently bound chlorine in organic compounds by solid
      state 35Cl NMR spectroscopy and exact spectral line-shape simulations.

PMID- 22419501
TI  - Effects of mechanical indentation on diffuse reflectance spectra, light
      transmission, and intrinsic optical properties in ex vivo porcine skin.
AB  - BACKGROUND AND OBJECTIVES: Mechanical indentation has been shown to increase
      light transmission through turbid tissue. In this study, we investigated the
      effects of localized indentation on the optical properties of ex vivo porcine
      skin specimens by dynamically monitoring diffuse reflectance spectra, light
      transmission, and applied load while controlling tissue thickness. STUDY
      DESIGN/METHODS: A custom-built diffuse reflectance spectroscopy (DRS) system was
      used to capture diffuse reflectance spectra from tissue specimens undergoing
      indentation. The DRS probe was designed to perform both optical sensing and
      tissue indentation. A mechanical load frame was used to dynamically control probe
      displacement and resultant specimen thickness change while recording applied
      load. Diffuse reflectance spectra, as well as light transmission at 630 nm, were
      recorded during stress relaxation tests where tissue specimens were displaced to
      and held at a final thickness. Tissue optical properties were extracted from
      reflectance spectra using a previously established look-up table (LUT) approach.
      RESULTS: Indentation increased light transmission through tissue during linear
      displacement, and continued to increase transmission during subsequent stress
      relaxation at constant tissue thickness. The magnitude of relative transmission
      increases was shown to be a function of bulk tissue compressive strain (relative
      thickness change). Reduced scattering coefficients calculated from the LUT at 630
      nm decreased during stress relaxation, with the relative decrease in scattering
      also depending strongly on tissue compressive strain. Reduced scattering
      coefficients decreased by 12.0 +/- 4.7% at 0.44 +/- 0.022 compressive strain, and
      reduced by 35.6 +/- 1.3% at 0.71 +/- 0.01 compressive strain. CONCLUSION: DRS can
      be used to capture transient changes in intrinsic tissue optical properties
      during mechanical loading. Mechanical indentation modifies tissue optical
      properties and may be harnessed as a minimally-invasive optical clearing
      technique to improve optical diagnostics and therapeutics.

PMID- 22419503
TI  - Released products of pathogenic bacteria stimulate biofilm formation by
      Escherichia coli K-12 strains.
AB  - It has recently been shown that pathogens with a limited capacity for sessile
      growth (like some Escherichia coli O157 strains) can benefit from the presence of
      other bacteria and form mixed biofilms with companion strains. This study
      addresses the question whether pathogens may influence attached growth of E. coli
      non-pathogenic strains via secreted factors. We compared the biofilm-modulating
      effects of sterile stationary-phase culture media of a biofilm non-producing
      strain of E. coli O157:H, a laboratory biofilm-producing E. coli K-12 strain and
      a biofilm-forming strain of the pathogen Yersina enterocolitica O:3. Sessile
      growth was monitored as biomass (crystal violet assay), exopolysaccharide (ELLA)
      and morphology (scanning electron and confocal laser microscopy). With two of the
      E. coli K-12 strains stimulation of biofilm formation by all supernatants was
      achieved, but only the pathogens' secreted products induced biomass increase in
      some 'biofilm-deficient' K-12 strains. Lectin-peroxidase labeling indicated
      changes in colanic acid and poly-N-acetylglucosamine amounts in extracellular
      matrices. The contribution of indole, protein and polysaccharide to the biofilm
      modulating activities of the supernatants was compared. Indole, in concentrations
      equal to those established in the supernatants, suppressed sessile growth in one
      K-12 strain. Proteinase K significantly reduced the stimulatory effects of all
      supernatants, indicating a prominent role of protein/peptide factor(s) in biofilm
      promotion. The amount of released polysaccharides (rPS) in the supernatants was
      quantitated then comparable quantities of isolated rPS were applied during
      biofilm growth. The three rPS had notable strain-specific effects with regard to
      both the strain-source of the rPS and the E. coli K-12 target strain.

PMID- 22419500
TI  - Genetic Risk and Outcome of Psychosis (GROUP), a multi-site longitudinal cohort
      study focused on gene-environment interaction: objectives, sample
      characteristics, recruitment and assessment methods.
AB  - OBJECTIVE: A longitudinal focus on gene-environment vulnerability and resilience
      in both patients, their unaffected family members and non-related controls offers
      the opportunity to elucidate etiological and pathogenetic factors influencing the
      onset and course of psychotic disorders. The current paper delineates the
      objectives, sample characteristics, recruitment and assessment procedures of the
      Genetic Risk and Outcome of Psychoses (GROUP) study. METHODS: A naturalistic
      longitudinal cohort study with assessments at baseline, after three and six years
      of follow-up. The study is conducted by a consortium of four university
      psychiatric centres, with their affiliated mental health care institutions in the
      Netherlands covering more than 7.5 million inhabitants. Extensive assessment of
      genetic factors, environmental factors, (endo)phenotypes, and outcome. RESULTS:
      At baseline, 1120 patients, 1057 siblings, 919 parents and 590 healthy controls
      were included. CONCLUSION: The GROUP study will contribute to insight in risk and
      protective factors in the aetiology of non-affective psychotic disorders, and in
      the variation in their course and outcome.

PMID- 22419504
TI  - A rapid and sensitive liquid chromatography-tandem mass spectrometric assay for
      moexipril, an angiotensin-converting enzyme inhibitor in human plasma.
AB  - A simple, rapid and sensitive liquid chromatography/tandem mass spectrometry
      method was developed and validated for the quantification of angiotensin
      converting enzyme inhibitor, moexipril, in human plasma. Benazepril was used as
      an internal standard (IS). Analyte and IS were extracted from the human plasma by
      liquid-liquid extraction technique using ethyl acetate. The reconstituted samples
      were chromatographed on a C18 column by using a mixture of methanol and 0.1%
      formic acid buffer (85:15, v/v) as the mobile phase at a flow rate of 0.5 mL/min.
      The calibration curve obtained was linear (r >= 0.99) over the concentration
      range of 0.2-204 ng/mL. The multiple reaction-monitoring mode was used for
      quantification of ion transitions at m/z 499.4/234.2 and 425.2/351.1 for
      moexipril and IS, respectively. The results of the intra- and inter-day precision
      and accuracy studies were well within the acceptable limits. A run time of 2.0
      min for each sample made it possible to analyze more than 400 plasma samples per
      day. The proposed method was found to be applicable to clinical studies.

PMID- 22419505
TI  - Clinical outcomes with contemporary endovascular therapy of iliac artery
      occlusive disease.
AB  - OBJECTIVES: We sought to evaluate the clinical outcomes of a consecutive series
      of patients treated for iliac artery occlusive disease (IAOD) using contemporary
      endovascular technology and techniques. BACKGROUND: As an increasingly complex
      spectrum of IAOD is treated using endovascular revascularization, there is a need
      to examine the rates of acute procedural success, complications, and patency to
      validate the role of an endovascular-first approach to revascularization in
      contemporary practice. METHODS: All patients with IAOD who were treated using
      endovascular therapy between September 2005 and September 2010 were identified
      from a prospectively collected database. Baseline patient characteristics,
      anatomic details, procedural data, and clinical outcomes were assessed
      retrospectively. Patency and mortality rates were estimated with the Kaplan-Meier
      method. RESULTS: A total 59 patients underwent 62 procedures. Trans-Atlantic
      Inter-Society Consensus (TASC) II types B, C, and D disease accounted for 59%,
      7%, and 37% of patients, respectively. The procedure was technically successful
      in 60 of 62 cases (97%) with no procedure-related mortality. Major complications
      occurred in five procedures (8%). The mean (+/-standard deviation) duration of
      follow-up was 2.3 +/- 1.4 years. In patients with a successful revascularization,
      primary and secondary patency rates were 86% and 94% at 1 year, and 77% and 91%
      at 2 years, respectively. The TASC II classification of disease did not predict
      the rate of acute technical success or medium-term patency rates. CONCLUSIONS:
      The acute and medium-term clinical outcomes of this series of patients with
      anatomically complex IAOD support the current paradigm of an endovascular-first
      approach to revascularization.

PMID- 22419506
TI  - HMG CoA reductase inhibitors, NSAIDs and risk of glioma.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins)
      have shown inverse associations with cancer risks, but the results have been
      inconsistent. As there are no previous published data in brain tumors, we
      conducted a case-control study to investigate statin therapy and risk of glioma.
      We further evaluated the use of nonsteriodal anti-inflammatory drugs (NSAIDs) and
      risk of these tumors. We recruited newly diagnosed glioma cases and frequency
      matched controls at Columbia University and the University of California San
      Francisco. Standardized questions on statins and NSAIDs were used at both
      institutions. Intakes of these drugs were defined as >6 months of at least twice
      weekly use versus less than this amount or never use. From July 2007 to January
      2010, we recruited a total of 517 cases and 400 controls. Simvastatin and
      lovastatin showed significant inverse associations with glioma (odds ratio [OR] =
      0.49, 95% confidence interval [CI] 0.30, 0.81 and OR = 0.47, 95% CI 0.24, 0.93,
      respectively). For NSAIDs, aspirin use was also inversely related to glioma risk
      (OR = 0.68, 95% CI 0.49, 0.96). Both statins and NSAIDs showed significant
      inverse trends between the duration of drug use and glioma risk (trend tests p =
      0.03 and p = 0.02, respectively), and drug intake for >120 months demonstrated
      the most significant associations for both types of medication. The inverse
      association between statin therapy and risk of glioma supports the roles of
      Ras/Rho GTPases or inflammatory cytokines in gliomagenesis, and a similar
      relationship between NSAIDs and glioma highlights the importance of cyclo
      oxygenase 2 in glioma pathogenesis.

PMID- 22419507
TI  - Relationships between gray matter, body mass index, and waist circumference in
      healthy adults.
AB  - Obesity and overweight are often defined by the body mass index (BMI), which
      associates with metabolic and cardiovascular disease, and possibly with dementia
      as well as variations in brain volume. However, body fat distribution and
      abdominal obesity (as measured by waist circumference) is more strongly
      correlated with cardiovascular and metabolic risk than is BMI. While prior
      studies have revealed negative associations between gray matter tissue volumes
      and BMI, the relationship with respect to waist circumference remains largely
      unexplored. We therefore investigated the effects of both BMI and waist
      circumference on local gray matter volumes in a group of 115 healthy subjects
      screened to exclude physical or mental disorders that might affect the central
      nervous system. Results revealed significant negative correlations for both BMI
      and waist circumference where regional gray matter effects were largest within
      the hypothalamus and further encompassed prefrontal, anterior temporal and
      inferior parietal cortices, and the cerebellum. However, associations were more
      widespread and pronounced for waist circumference than BMI. Follow-up analyses
      showed that these relationships differed significantly across gender. While
      associations were similar for both BMI and waist circumference for males, females
      showed more extensive correlations for waist circumference. Our observations
      suggest that waist circumference is a more sensitive indicator than BMI,
      particularly in females, for potentially determining the adverse effects of
      obesity and overweight on the brain and associated risks to health.

PMID- 22419508
TI  - TRPV4-pathy manifesting both skeletal dysplasia and peripheral neuropathy: a
      report of three patients.
AB  - Heterozygous missense mutations of transient receptor potential vanilloid 4
      channel (TRPV4) cause a spectrum of skeletal disorders, including brachyolmia,
      spondylometaphyseal dysplasia Kozlowski type, metatropic dysplasia,
      parastremmatic dysplasia, and spondyloepimetaphyseal dysplasia Maroteaux type.
      Similarly, heterozygous missense mutations of TRPV4 cause a spectrum of
      peripheral neuropathy, including hereditary motor and sensory neuropathy type
      IIC, congenital spinal muscular atrophy, and scapuloperoneal spinal muscular
      atrophy. There are no apparent differences in the amino acid positions affected
      or type of change predicted by the TRPV4 mutations responsible for the two
      disease spectrums; nevertheless, no fundamental phenotypic overlap has been shown
      between the two spectrums. Here, we report on three patients who had both
      skeletal dysplasia and peripheral neuropathy caused by heterozygous TRPV4
      missense mutations. The skeletal and neurologic phenotypes of these patients
      covered the wide spectrum of reported TRPV4-pathies (disease caused by TRPV4
      mutations). The molecular data are complementary, proving that "neuropathic"
      mutations can cause skeletal dysplasia but also the "skeletopathic" mutations can
      lead to neuropathies. Our findings suggest that pathogenic mechanisms of TRPV4
      pathies in skeletal and nervous systems are not always mutually exclusive and
      provide further evidence that there is no clear genotype-phenotype correlation
      for either spectrum. Co-occurrence of skeletal dysplasia and degenerative
      neuropathy should be kept in mind in clinical practice including diagnostic
      testing, surgical evaluation, and genetic counseling.

PMID- 22419510
TI  - Electronic modulation of a copper/zinc oxide catalyst by a heterojunction for
      selective hydrogenation of carbon dioxide to methanol.

PMID- 22419509
TI  - A multicenter prospective observational study of the conformity of temozolomide
      prescriptions in France.
AB  - CONTEXT: Temozolomide (TMZ) is approved for the treatment of high-grade gliomas
      such as glioblastoma (GBM) multiforme and refractory anaplastic astrocytoma, but
      it is also used in indications not mentioned in the summary of product
      characteristics (SPC). The main objective of this study was to evaluate the
      conformity of TMZ prescriptions to the French SPC and prescription guidebook.
      METHODS: We conducted a prospective observational study of all consecutive
      patients treated with TMZ in 21 French hospitals between September 2006 and
      February 2007, accounting for 39% of total TMZ consumption in France. The
      conformity of TMZ prescriptions was evaluated in terms of the indication, dosage,
      treatment duration, and combination with other treatments, with respect to the
      SPC and prescription guidebook. RESULTS: We enrolled 831 patients (median age, 56
      years) who received a total of 5982 TMZ treatment cycles. TMZ was mainly
      prescribed to patients with newly diagnosed GBM (384 patients), GBM in
      progression/relapse (28 patients), or anaplastic astrocytoma in
      progression/relapse (19 patients). Prescriptions conformed to the SPC in 51.9% of
      cases and to the prescription guidebook in 91.5% of cases. Global conformity with
      the SPC, in terms of the dosage, treatment duration, and combination with other
      treatments, was 62% for newly diagnosed GBM treated with radiotherapy plus TMZ,
      72% for TMZ maintenance monotherapy, and 66% for GBM and anaplastic astrocytoma
      in progression/relapse. CONCLUSION/DISCUSSION: In France, routine TMZ
      prescriptions conform to the SPC and practice guidebook. This is one of the
      largest studies of drug use in neuro-oncology in terms of the number of patients
      and cycles analyzed.

PMID- 22419511
TI  - Conflict of evidence: carotenoids and other micronutrients in the prevention and
      treatment of cognitive impairment.
AB  - Cognitive impairment is a common age-related disorder which affects in the
      stadium and type Alzheimer's Disease (AD) a steadily growing number of patients.
      AD is not curable and is not being easily diagnosed in its preclinical phase.
      This work aims at highlighting the complex though promising rationale for the use
      of selected micronutrients against age-related cognitive impairment and its
      progression. The advances made in the last decades in both defining the
      etiopathogenesis of cognitive impairment and in revealing mechanisms of action
      underlying possible preventive effects of several vitamins and micronutrients-
      likely related to antioxidant activity and modulation of cellular signaling--is
      being accompanied by conflicting results of most clinical trials. Therefore,
      available data do not currently support the use of substances such as
      carotenoids, polyphenols, vitamin D, curcumin, vitamin E, vitamin C, or lipoic
      acid in AD prevention and/or treatment. This might be partly due to the fact that
      cognitive impairment and especially AD are extremely complex disorders. The main
      obstacle to the inclusion of micronutrients among anticognitive impairment drug
      strategies, however, is that studies conducted so far are poorly comparable and
      probably underestimate of the role of vascular damage in age-related cognitive
      impairment. A possible clinical benefit of these substances in AD is not
      disproved to date, thus further better designed studies are needed.

PMID- 22419512
TI  - Do we always prioritize balance when walking? Towards an integrated model of task
      prioritization.
AB  - Previous studies suggest that strategies such as "posture first" are implicitly
      employed to regulate safety when healthy adults walk while simultaneously
      performing another task, whereas "posture second" may be inappropriately applied
      in the presence of neurological disease. However, recent understandings raise
      questions about the traditional resource allocation concept during walking while
      dual tasking. We propose a task prioritization model of walking while dual
      tasking that integrates motor and cognitive capabilities, focusing on postural
      reserve, hazard estimation, and other individual intrinsic factors. The proposed
      prioritization model provides a theoretical foundation for future studies and a
      framework for the development of interventions designed to reduce the profound
      negative impacts of dual tasking on gait and fall risk in patients with
      neurological diseases. (c) 2012 Movement Disorder Society.

PMID- 22419513
TI  - Microbial profiles of patients seeking treatment for periodontitis. Influence of
      origin, smoking and age?
AB  - PURPOSE: We assessed the potential influence of the origin, the smoking status
      and the age on subgingival microbial profiles of subjects seeking periodontal
      care in Switzerland today. MATERIAL AND METHODS: Subgingival samples were
      obtained from 182 subjects originating from 44 countries (56 native Swiss, 64
      other European, 43 African, 19 others), seeking periodontal treatment at the
      School of Dental Medicine at the University of Geneva. Four periodontal
      microorganisms were quantified by direct hybridization with specific RNA probes.
      RESULTS: Tannerella forsythia and Treponema denticola were ubiquitous (95.6%,
      93.9%), and Porphyromonas gingivalis was frequently detected (89%). Counts
      correlated with the size of the microbial sample (total load). Aggregatibacter
      actinomycetemcomitans was detected in only 70 (38.4%) subjects. Counts were
      highly variable and unrelated to total load. Subjects less than 46.8 years old
      (median age) had a higher risk to be positive than older subjects. Detection
      frequencies and counts of all four organisms were unrelated to the origin or the
      smoking status. CONCLUSIONS: Based on a clinical diagnosis of untreated
      periodontitis, positive outcomes of tests for T. forsythia, T. denticola and P.
      gingivalis could be predicted with high confidence irrespective of a patient;'s
      origin, smoking status or age. Detection of A. actinomycetemcomitans was less
      frequent and depended on the age of the subject.

PMID- 22419514
TI  - Imposing respiratory variability patterns.
AB  - To ensure respiratory stability and flexibility, healthy breathing shows balanced
      variability consisting of considerable correlated variability (parameters of each
      breath are correlated to parameters of adjoining breaths) and some random
      variability. Sighing resets this balance when respiration lacks variability or
      becomes excessively irregular. The present study aimed to investigate the effect
      of imposed patterns of breathing variability on sighing and self-reported
      (dis)comfort. Spontaneous breathing was compared to imposed non-variable,
      correlated and random breathing. Results show that executing imposed breathing is
      difficult, demanding, and induces tension. Sigh occurrence following spontaneous
      and imposed breathing patterns could be predicted by self-reported discomfort and
      increased random variability. However, including non-variable, correlated and
      random breathing patterns only, the effects of self-reported discomfort on sigh
      occurrence override the effects of altered breathing variability.

PMID- 22419515
TI  - Empathy in cooperative versus non-cooperative situations: the contribution of
      self-report measures and autonomic responses.
AB  - Shared representations, emotion comprehension, and emotion regulation constitute
      the basic macro components of social empathy. The present study integrated two
      different measures of empathic behavior in a social context: verbal self-report
      measures (empathic response, emotional involvement and emotional significance,
      and valence), and autonomic responses (facial expression-corrugator supercilii
      and zygomaticus major muscle-, SCR-skin conductance-, and HR-heart rate-).
      Participants (N = thirty-five) were presented with different interpersonal scene
      types (cooperation, non-cooperation, conflict, indifference). Different empathic
      sensitivity to these interpersonal situations was verified, since self-rating on
      empathy, emotional involvement and valence varied as a function of interpersonal
      context. Situation rated as more empathically significant were considered also as
      the most positive (cooperation) and negative (non cooperation and conflictual)
      and emotionally significant (high emotional significance of the scenes) in
      comparison with neutral scenes. Nevertheless, subjective empathic response and
      personal emotional involvement were found to be dissociated measures in non
      cooperative condition. On the autonomic level, facial mimicry was linked to and
      coherent with the empathic response in cooperative, non-cooperative and
      conflictual conditions, whereas SCR and HR were increased only in response to
      cooperative and conflictual situation, rated as more involving by the subject.
      The convergence of these multidimensional measures was discussed: empirical
      evidences are far from able to warrant claims that processes of emotional
      contagion and simulation provide the sole, primary important way by which we come
      to know what others are feeling.

PMID- 22419516
TI  - Does reference value of "Normal Liver Stiffness" using fibroscan have a regional
      variation?

PMID- 22419517
TI  - Percutaneous interventions in high-risk patients following Mustard repair of
      transposition of the great arteries.
AB  - OBJECTIVES: To assess safety, efficacy, and intermediate term outcomes of
      percutaneous interventions in Mustard patients. BACKGROUND: Baffle leaks and
      obstruction are present in 20% of Mustard survivors. Surgical reintervention is
      associated with high mortality. METHODS: Retrospective review of percutaneous
      interventions performed at three adult congenital catheterization programs.
      RESULTS: Overall, 26 catheterizations and 29 interventions were performed in 22
      patients (mean age 32.4 +/- 8.3 years). Previous laser pacemaker lead extraction
      was successful in seven of seven procedures where the lead was at risk. Stent
      placement was successful in all 18 patients with systemic venous baffle (SVB)
      obstruction (mean gradient: 6.2 +/- 3.4-0.6 +/- 1.0 mm Hg; P < 0.01, narrowest
      diameter 4.5 +/- 4.5-17.1 +/- 3.9 mm; P < 0.01). Balloon angioplasty was
      performed in two patients for pulmonary venous baffle (PVB) obstruction with
      mixed results. Baffle leak interventions included device occlusion (n = 6), coil
      occlusion (n = 1), and covered stent occlusion (n = 3). Postprocedural residual
      leaks were demonstrated in three of eight. In two of the three the residual leak
      was not appreciable at 1-year follow-up. No patient experienced leak or
      obstruction related symptom recurrence (mean follow-up: 33.4 +/- 29.5 months).
      Complications included one death secondary to ventricular arrhythmia 2 days after
      PVB angioplasty and device related inferior SVB obstruction with resolution
      following stent placement. CONCLUSIONS: Stent placement for SVB obstruction
      following Mustard repair is effective and likely safer than surgical
      intervention. Baffle leak occlusion can be safely accomplished but residual leaks
      are common in the short term.

PMID- 22419518
TI  - Enhancement of natural killer cell effector functions against selected lymphoma
      and leukemia cell lines by dasatinib.
AB  - As NK cell immunotherapy is still poorly successful, combinations with drugs
      enhancing NK cell activity are of major interest. NK large granular lymphocyte
      expansions associated with improved survival have been described under
      monotherapy with the Bcr-Abl/Src inhibitor dasatinib, which inhibits NK cell
      functions in vitro. As Src kinases play a major role in inhibitory and activating
      signaling pathways of NK cells, both outcomes appear plausible. To clarify these
      contradictory observations and potentially enable the use of dasatinib as
      adjuvant, we analyzed how clinically relevant doses promote NK cell effector
      functions. Polyclonal human NK cells were studied ex vivo. Functional outcomes
      assessed included conjugate formation, calcium flux, receptor regulation,
      cytokine production, degranulation, cytotoxicity, apoptosis induction and signal
      transduction. While dasatinib inhibits NK cell effector functions during
      functional assays, 24 hr pretreatment of NK cells followed by washout of
      dasatinib, led to dose-dependent enhancement of cytokine production,
      degranulation marker expression and cytotoxicity against selected lymphoma and
      leukemia cell lines. Mechanistically, this was neither due to an altered
      viability of NK cells nor increased NKG2D, LFA-1 or conjugate formation with
      target cells. Receptor proximal signaling events were inhibited. However, a
      slight time dependent enhancement of Vav phosphorylation was observed under
      certain circumstances. The shift in Vav phosphorylation level may be one major
      mechanism for NK cell activity enhancement induced by dasatinib. Our findings
      argue for a careful timing and dosing of dasatinib application during
      leukemia/lymphoma treatment to enhance NK cell immunotherapeutic efforts.

PMID- 22419519
TI  - Impact of the Reelin signaling cascade (ligands-receptors-adaptor complex) on
      cognition in schizophrenia.
AB  - Our previous neurocognitive studies of schizophrenia outlined two clusters of
      affected subjects--cognitively spared (CS) and cognitive deficit (CD), the
      latter's characteristics pointing to developmental origins and impaired synaptic
      plasticity. Here we investigate the contribution of polymorphisms in major
      regulators of these processes to susceptibility to schizophrenia and to CD in
      patients. We examine variation in genes encoding proteins at the gateway of
      Reelin signaling: ligands RELN and APOE, their common receptors APOER2 and VLDLR,
      and adaptor DAB1. Association analysis with disease outcome and cognitive
      performance in the Western Australian Family Study of Schizophrenia (WAFSS) was
      followed by replication analysis in the Australian Schizophrenia Research Bank
      (ASRB) and in the Health in Men Study (HIMS) of normal aging males. In the WAFSS
      sample, we observed significant association of APOE, APOER2, VLDLR, and DAB1 SNPs
      with disease outcome in the case-control and CD-control datasets, and with pre
      morbid intelligence and verbal memory in cases. HIMS replication analysis
      supported rs439401 (APOE regulatory region), and rs2297660 and rs3737983
      (APOER2), with an effect on memory performance in normal aging subjects
      consistent with the findings in schizophrenia cases. APOER2 gene expression
      analysis revealed lower transcript levels in lymphoblastoid cells from
      cognitively impaired schizophrenia patients of the alternatively spliced exon 19,
      mediating Reelin signaling and synaptic plasticity in the adult brain. ASRB
      replication analysis produced marginally significant results, possibly reflecting
      a recruitment strategy biased toward CS patients. The data suggest a contribution
      of neurodevelopmental/synaptic plasticity genes to cognitive impairment in
      schizophrenia.

PMID- 22419520
TI  - "Let momma take 'em": portrayals of women supporting male former prisoners.
AB  - Women provide support for many vulnerable groups, work that is frequently
      discounted with gendered stereotypes. One growing vulnerable group is former
      prisoners who often return to women family members. We completed a qualitative
      study with 25 former prisoners and criminal justice staff to examine their
      conceptualizations of the demands placed on women supporters of former prisoners.
      Results indicate a significant burden of support experienced by women, discounted
      by prisoners and criminal justice staff through a dynamic of gendered
      idealization and stigmatization. Implications include the importance of exposing
      this dynamic and providing supports to decrease the burden of care that women
      experience.

PMID- 22419521
TI  - Violence against Chinese female sex workers in Hong Kong: from understanding to
      prevention.
AB  - Violence against sex workers is considered a global phenomenon. Despite this,
      very little is known about the patterns and nature of this form of violence. This
      article is concerned with violence against Chinese female sex workers in Hong
      Kong. Based on a systematic analysis of 75 police case files, it was found that
      violent attacks on sex workers display clear temporal and spatial patterns, and
      that perpetrators share certain characteristics. The article concludes that
      violence against female sex workers in the Chinese context is largely opportunity
      driven and goes on to argue that situational measures offer the greatest
      potential for preventive gains. Barriers to effective implementation such as the
      inappropriate or unfavourable responses of the government, the police, community
      leaders, and local residents toward commercial sexual activity are also
      discussed.

PMID- 22419522
TI  - Sociolegal characteristics and parole infractions among Israeli released
      prisoners during electronic monitoring.
AB  - The objective of this study is to examine the part played by sociolegal
      characteristics such as ethnic background, family status, or criminal past in the
      rate of infractions among ex-prisoners in Electronic Monitoring (EM) Programs. In
      addition, it focuses on the nature of the formal decisions made by community
      supervision agents regarding such infractions and their correlation with the
      sociolegal characteristics of the participants. The research population included
      all prisoners on license (i.e., prisoners who have been granted conditional early
      release) who took part in the EM project from mid-2007 until mid-2009 (24
      months), altogether 155 participants. The data show no significant correlation
      between the number of infractions and the participant's sociolegal background. In
      spite of the fact that the EM coordinators have extensive discretionary power,
      which is likely to lead to discrimination attributable to variables such as
      ethnicity, this research shows that the most efficacious variable for explaining
      formal responses is an objective one-the number of infractions.

PMID- 22419523
TI  - Social bias and the development of self-control: results from a longitudinal
      study of children and adolescents.
AB  - Gottfredson and Hirschi's general theory of crime has sparked a tremendous amount
      of research examining the link between levels of self-control and involvement in
      delinquent and criminal acts. Recently, studies testing this theory have begun to
      investigate the factors that are related to the development of self-control. The
      current study expands on this body of research by examining whether social bias,
      as measured by the ability to identify facial expressions, contributes to
      variation in self-control in a sample of children. Analysis of data drawn from
      the National Survey of Children revealed some evidence that children who had
      difficulty correctly identifying facial expressions depicting fear and happiness
      had lower levels of self-control, whereas errors in identifying faces expressing
      anger were related to higher levels of self-control. The authors discuss the need
      for Gottfredson and Hirschi's theory on the development of self-control to be
      expanded.

PMID- 22419525
TI  - Chemical protein synthesis by chemoselective alpha-ketoacid-hydroxylamine (KAHA)
      ligations with 5-oxaproline.

PMID- 22419524
TI  - Right, left, and center: how does cerebral asymmetry mix with callosal
      connectivity?
AB  - BACKGROUND: Prior research has shown that cerebral asymmetry is associated with
      differences in corpus callosum connectivity. Such associations were detected in
      histological and anatomical studies investigating callosal fiber size and
      density, in neuroimaging investigations based on structural and diffusion tensor
      imaging, as well as in neuropsychological experiments. However, little is known
      about typical associations between these factors, and even less about the
      relative influences of magnitude and direction of cerebral asymmetries. Here, we
      investigated relationships between callosal connectivity and cerebral asymmetry
      using precise measures of callosal thickness and selected cerebral structures. We
      considered both the direction and magnitude of the asymmetries. METHODS:
      Associations between cerebral asymmetry and callosal thickness were investigated
      in 348 cognitively healthy older individuals. RESULTS: The magnitude and
      direction of cerebral lateralization were significant independent predictors of
      callosal thickness. However, associations were small. Leftward asymmetry and
      increased magnitude of asymmetry were generally associated with increased
      callosal thickness, mostly in the callosal midbody and isthmus. CONCLUSIONS: When
      a large sample of normal individuals is considered, cerebral asymmetries are only
      subtly associated with callosal thickness.

PMID- 22419526
TI  - Increased levels of 5-HT1A receptor binding in ventral visual pathways in
      Parkinson's disease.
AB  - Visual hallucinations are common in advanced Parkinson's disease (PD). The
      pathophysiology of visual hallucinations may involve enhanced serotonergic
      neurotransmission. The atypical antipsychotics clozapine and quetiapine, which
      have affinity for 5-HT(2A) and 5-HT(1A) receptors, are effective against visual
      hallucinations in PD. 5-HT(2A) receptors are increased in ventral visual pathways
      in PD patients with visual hallucinations, and we hypothesized that 5-HT(1A)
      receptors were also involved in visual hallucinations in PD. Autoradiographic
      binding using [(3) H]-WAY-100,635 and NAN-190 was performed in brain sections
      from 6 PD patients with visual hallucinations, 6 PD patients without visual
      hallucinations, and 5 age-matched controls. All PD subjects had been treated with
      L-dopa. Brain areas studied were the orbitofrontal, inferolateral temporal, and
      motor cortices, as well as the striatum, globus pallidus, substantia nigra, and
      thalamus. 5-HT(1A) -binding levels were dramatically increased in the ventral
      visual pathways of all PD patients compared with controls (0 vs 11 and 0 vs 100
      nmol/mg, respectively; both P < .05). There was no significant difference in 5
      HT(1A) -binding levels in PD patients with visual hallucinations compared with PD
      patients without visual hallucinations or with controls in any of the brain areas
      studied (P > .05). Gross abnormalities in 5-HT(1A) levels in ventral visual areas
      occurred in all PD patients exposed to L-dopa. However, as there was no
      difference in 5-HT(1A) -binding levels between hallucinators and
      nonhallucinators, alterations in 5-HT(1A) receptor levels may not contribute
      specifically to visual hallucinations in PD. However, the discrete anatomical
      distribution of rises to the ventral visual areas suggests some role in
      predisposing to visual hallucinations.

PMID- 22419527
TI  - Ascorbic acid, cognitive function, and Alzheimer's disease: a current review and
      future direction.
AB  - This narrative review appraises the human and animal studies implicating ascorbic
      acid (AA) in normal cognitive function and Alzheimer's disease. A research
      framework for how nutrition affects brain aging is proposed with emphasis on AA
      intake, status, metabolism, and transport into brain tissue. A final synopsis
      highlights areas for future research regarding AA nourishment and healthy brain
      aging.

PMID- 22419528
TI  - Cardiovascular outcomes in women with advanced breast cancer exposed to
      chemotherapy.
AB  - PURPOSE: To quantify incidence of cardiovascular outcomes in patients with
      advanced breast cancer receiving cardiotoxic and non-cardiotoxic chemotherapy.
      METHODS: This study identified all women at a Midwestern health system with
      initial diagnosis of American Joint Commission on Cancer Stage III/IV breast
      cancer (1995-2003) and random sample of 50 women initially diagnosed with Stage
      I/II who progressed to Stage III/IV. The rate of new cardiovascular outcomes
      (heart failure, dysrhythmia, and ischemia events) for cardiotoxic (anthracycline
      or trastuzumab) and non-cardiotoxic agents was calculated. RESULTS: Of 315
      patients, 90.5% (n = 285) received systemic cancer therapy; 67.7% (n = 193)
      received cardiotoxic drugs. Older patients were less likely to receive
      cardiotoxic agents (86.4%, <=59 years vs. 31.9%, 70+ years). Adjusting for age,
      race, stage, surgery/radiation, estrogen receptor/progesterone receptor status,
      and diagnosis year, rate of new cardiac events was higher in patients exposed to
      cardiotoxic drugs compared with those exposed to non-cardiotoxic drugs (adjusted
      hazard ratio = 2.5, 95%CI = 0.9-7.2). Patients with cardiac event history
      (relative risk = 3.2, 95%CI = 2.0-5.1) and those with heart failure history
      (relative risk = 5.9, 95%CI = 2.4-14.6) were more likely to receive non
      cardiotoxic treatment. Heart failure events occurred steadily over time; after 3
      years of follow-up, 16% exposed to cardiotoxic drugs experienced an event, and 8%
      of those exposed to non-cardiotoxic drugs experienced an event. CONCLUSIONS:
      Patients with cardiac comorbidity are less likely to receive cardiotoxic agents.
      Use of cardiotoxic agents is common; treatment is related to patient and tumor
      characteristics and is associated with substantial risk of cardiotoxicity that
      persists during patients' remaining lifespan.

PMID- 22419531
TI  - Carotenoids in nutrition and health-developments and future trends.

PMID- 22419529
TI  - High-field magneto-photoluminescence of semiconductor nanostructures.
AB  - We review the photoluminescence of semiconductor nanostructures in high magnetic
      fields, concentrating on the effects of the applied magnetic field on orbital
      motion (wave function extent), which is probed in experiments on large ensembles.
      We present an overview of the physics of excitons in high magnetic fields in 3-
      and 2-D before introducing the zero-dimensional case. We then discuss the physics
      of quantum-dot excitons in high magnetic fields with particular attention to the
      approximate analytical models used to interpret experimental results. This is
      followed by a brief description of a typical high-field magneto-photoluminescence
      setup. We then present four examples of magneto-photoluminescence experiments on
      different materials systems chosen from our own research to illustrate how high
      magnetic fields can be used to reveal new insights into the physics of
      semiconductor nanostructures.

PMID- 22419532
TI  - Lycopene and heart health.
AB  - Cardiovascular diseases (CVDs) are the leading causes of human morbidity and
      mortality in developed countries. Specific biomarkers in this context are markers
      of inflammation, lipid status, thrombosis and oxidative stress. One
      recommendation for CVD prevention is to increase consumption of fruits and
      vegetables as good sources of secondary plant products, e.g. carotenoids. This
      review aimed to show linkages between lycopene, one main carotenoid in the human
      diet, and prevention of heart diseases by looking for epidemiological data,
      results from in vitro experiments and results from in vivo studies (animal
      studies and human intervention trials). In addition, patents and products within
      the context of lycopene and CVD prevention will be discussed with a special
      emphasis on health claims. Epidemiological data, in vitro data and results from
      animal experiments partly showed promising preventive mechanisms of lycopene. In
      contrast, until now, human intervention studies mostly failed to show any CVD
      prevention. However, there is still an encouraging situation, giving hints for
      antioxidant as well as anti-inflammatory effects of lycopene. These mechanisms
      could be the background for cardio-protective effects of tomatoes and tomato
      products. In summary, there are a lot of investigations needed in the future to
      give reliable results to establish these CVD-preventive effects.

PMID- 22419533
TI  - A moderate red wine intake improves blood lipid parameters and erythrocytes
      membrane fluidity in post myocardial infarct patients.
AB  - While the cardioprotective effect of moderate and regular wine consumption in
      primary prevention has been well documented, the goal of the present
      investigation was to explore the effect of wine intake on blood parameters
      (lipid, anti-oxidant capacity, and erythrocyte membrane potential and fluidity)
      in post myocardial infarct patients to evaluate perspectives in secondary
      prevention. A clinical intervention trial has been undertaken on a group of
      selected post myocardial infarct patients who gave written informed consent for
      participation in this study prior to enrolment. This two-week study has been
      conducted on hospitalized patients during a cardiac readaptation period. During
      this period, patients were submitted to a "Western prudent" diet (inspired by the
      Mediterranean diet) and two groups have been compared on a drawn basis: patients
      receiving red wine (250 mL daily) to patients receiving water. Physical,
      clinical, and blood parameters were evaluated on Days 1 and 14. The data show a
      positive effect of low wine consumption on blood parameters (decrease in total
      cholesterol and LDL; increase in erythrocyte membrane fluidity and antioxidant
      status). The results show that a moderate consumption of red wine even for a
      short period associated with a "Western prudent" diet improves various blood
      parameters in lipid and anti-oxidative status in patients with previous coronary
      ischemic accidents.

PMID- 22419534
TI  - Structural analysis of oval-cell-mediated liver regeneration in rats.
AB  - We have analyzed the architectural aspects of progenitor-cell-driven regenerative
      growth in rat liver by applying the 2-acetaminofluorene/partial hepatectomy
      experimental model. The regeneration is initiated by the proliferation of so
      called oval cells. The oval cells at the proximal tips of the ductules have a
      more differentiated phenotype and higher proliferative rate. This preferential
      growth results in the formation of a seemingly random collection of small
      hepatocytes, called foci. These foci have no clonal origin, but possess a highly
      organized structure, which shows similarities to normal hepatic parenchyma.
      Therefore, they can easily remodel into the lobular structure. Eventually, the
      regenerated liver is constructed by enlarged hepatic lobules; no new lobules are
      formed during this process. The foci of the Solt-Farber experimental
      hepatocarcinogenesis model have identical morphological features; accordingly,
      they also represent only regenerative, not neoplastic, growth. CONCLUSION:
      Progenitor-cell-driven liver regeneration is a well-designed, highly organized
      tissue reaction, and better comprehension of the architectural events may help us
      to recognize this process and understand its role in physiological and
      pathological reactions.

PMID- 22419535
TI  - Spatial MEG laterality maps for language: clinical applications in epilepsy.
AB  - Functional imaging is increasingly being used to provide a noninvasive
      alternative to intracarotid sodium amobarbitol testing (i.e., the Wada test).
      Although magnetoencephalography (MEG) has shown significant potential in this
      regard, the resultant output is often reduced to a simplified estimate of
      laterality. Such estimates belie the richness of functional imaging data and
      consequently limit the potential value. We present a novel approach that utilizes
      MEG data to compute "complex laterality vectors" and consequently "laterality
      maps" for a given function. Language function was examined in healthy controls
      and in people with epilepsy. When compared with traditional laterality index (LI)
      approaches, the resultant maps provided critical information about the magnitude
      and spatial characteristics of lateralized function. Specifically, it was
      possible to more clearly define low LI scores resulting from strong bilateral
      activation, high LI scores resulting from weak unilateral activation, and most
      importantly, the spatial distribution of lateralized activation. We argue that
      the laterality concept is better presented with the inherent spatial sensitivity
      of activation maps, rather than being collapsed into a one-dimensional index.

PMID- 22419536
TI  - Plasma clozapine and norclozapine in relation to prescribed dose and other
      factors in patients aged 65 years and over: data from a therapeutic drug
      monitoring service, 1996-2010.
AB  - OBJECTIVE: To investigate the effect of dose and other factors on plasma
      clozapine concentrations in patients aged 65 years and over. METHOD: Audit of
      clozapine therapeutic drug monitoring data, 1996-2010. RESULTS: There were 1930
      samples [778 patients, 363 men aged (median, range) 67 (65-100) years and 415
      women aged 68 (65-90) years]. There was no significant difference in the mean
      plasma clozapine concentration between men (0.56 mg/l) and women (0.58 mg/l),
      although the mean dose was higher in men (323 mg/d) than women (264 mg/d). The
      higher proportion of men (46%) compared with women (37%) smokers could explain
      this finding. Overall, 32% of samples had plasma clozapine below, and 37% above,
      a target range of 0.35-0.60 mg/l. Overall, the median dose decreased from 300 (65
      70 years) to 200 mg/d (age 85 years and over). However, prescription of >350 mg/d
      was associated with a 50% likelihood that the plasma clozapine would exceed 0.60
      mg/l. For a subgroup of 196 patients (114 men, 82 women), mean plasma clozapine
      was significantly higher after age 65 despite significantly lower dosage.
      CONCLUSION: Clozapine dosage in elderly patients should be reviewed regularly to
      minimise the risk of adverse effects.

PMID- 22419537
TI  - Evasion of human innate immunity without antagonizing TLR4 by mutant Salmonella
      enterica serovar Typhimurium having penta-acylated lipid A.
AB  - Modification of a lipid A moiety in Gram-negative bacterial LPS to a less
      acylated form is thought to facilitate bacterial evasion of host innate immunity,
      thereby enhancing pathogenicity. The contribution of less-acylated lipid A to
      interactions of whole bacterial cells with host cells (especially in humans)
      remains unclear. Mutant strains of Salmonella enterica serovar Typhimurium with
      fewer acylated groups were generated. The major lipid A form in wild-type (WT)
      and the mutant KCS237 strain is hexa-acylated; in mutant strains KCS311 and
      KCS324 it is penta-acylated; and in KCS369 it is tetra-acylated. WT and KCS237
      formalin-killed and live bacteria, as well as their LPS, strongly stimulated
      production of pro-inflammatory cytokines in human U937 cells; this stimulation
      was suppressed by TLR4 suppressors. LPS of other mutants produced no agonistic
      activity, but strong antagonistic activity, while their formalin-killed and live
      bacteria preparations had weak agonistic and no antagonistic activity. Moreover,
      these less-acylated mutants had increased resistance to phagocytosis by U937
      cells. Our results indicate that a decrease of one acyl group (from six to five)
      is enough to allow Salmonella to evade human innate immunity and that the
      antagonistic activity of less-acylated lipid A is not utilized for this evasion.

PMID- 22419539
TI  - Mental adjustment at different phases in breast cancer trajectory: re-examination
      of factor structure of the Mini-MAC and its correlation with distress.
AB  - OBJECTIVE: The aim of this study is twofold. First, it aims to determine the
      factor structure of the Mini-Mental Adjustment to Cancer (Mini-MAC) Scale by
      using confirmatory factor analysis (CFA) to compare the three-factor, four
      factor, and five-factor structures among 340 Taiwanese breast cancer patients.
      Second, it aims to test the difference in the correlations of coping strategies
      and the outcome measures between two populations: one-month newly diagnosed and
      five-year long-term survival patients. METHODS: Two samples, composed of 142
      newly diagnosed and 198 long-term survival breast cancer patients, were
      recruited. Cancer-specific coping and distress were assessed via the Mini-MAC
      Scale and the Hospital Anxiety and Depression Scale (HADS), respectively.
      RESULTS: The CFA confirmed Watson's original five-factor structure fit the data
      best. The correlation difference between the two samples lies in the fighting
      spirit (FS), which correlated negatively with distress among the newly diagnosed
      sample but had no correlation among the long-term survivors. Moreover, fatalism
      (FA) was found to correlate positively with distress. CONCLUSIONS: The five
      factor structure represents a more psychometrically sound measure of
      psychological adjustment in the current data set. The findings also support the
      argument that the relationships between coping and distress vary, to some degree,
      at different phases in the cancer trajectory. FS is only a positive predictor of
      psychological adjustment among newly diagnosed patients. Because of the exclusion
      of two items, FA showed a positive correlation with distress, a result that
      contradicts previous findings. Further theoretical and practical implications for
      FS and FA are discussed.

PMID- 22419540
TI  - Selenium and cognitive impairment: a brief-review based on results from the EVA
      study.
AB  - Preventing cognitive impairment and dementia in the elderly is a major public
      health challenge for our century and all hypotheses should be explored. Selenium
      (Se) is one of the factors that may affect the risk of cognitive decline. Its
      importance in the health and aging process has been documented. Because of the
      potential of selenoproteins to protect against oxidative stress, Se raises
      significant expectations for the prevention of chronic diseases including cancer,
      cardiovascular disease, and type 2 diabetes conditions commonly associated with
      oxidative stress. Thus, the relationships between Se and cognitive impairment or
      dementia can be examined through vascular risk factors for dementia, with
      particular interest in diabetes and dyslipidemia. In addition, in cases of Se
      deficiency, the brain is the organ that remains Se replete the longest suggesting
      that Se plays an important role in brain functions. This article presents results
      obtained in the frame of a longitudinal study on Se and cognitive impairment.
      They are consistent with the hypothesis that low Se status is a risk factor for
      cognitive decline even after taking into account vascular risk factors. The
      concomitant evolution between plasma Se decrease over a 9-year period and
      cognitive decline suggested that optimal Se status is potentially important to
      maintain neuropsychological functions in aging people. However, as our
      understanding of Se biology is incomplete, epidemiological studies are needed to
      define the groups of population that could benefit from Se supplementation.

PMID- 22419541
TI  - Well-being in the Global Agenda.

PMID- 22419542
TI  - Incremental growth of short SWNT arrays by pulsed chemical vapor deposition.
AB  - Very short arrays of continuous single-wall carbon nanotubes (SWNTs) are grown
      incrementally in steps as small as 25 nm using pulsed chemical vapor deposition
      (CVD). In-situ optical extinction measurements indicate that over 98% of the
      nanotubes reinitiate growth on successive gas pulses, and high-resolution
      transmission electron microscopy (HR-TEM) images show that the SWNTs do not
      exhibit segments, caps, or noticeable sidewall defects resulting from repeatedly
      stopping and restarting growth. Time-resolved laser reflectivity (3-ms temporal
      resolution) is used to record the nucleation and growth kinetics for each fast
      (0.2 s) gas pulse and to measure the height increase of the array in situ,
      providing a method to incrementally grow short nanotube arrays to precise
      heights. Derivatives of the optical reflectivity signal reveal distinct temporal
      signatures for both nucleation and growth kinetics, with their amplitude ratio on
      the first gas pulse serving as a good predictor for the evolution of the growth
      of the nanotube ensemble into a coordinated array. Incremental growth by pulsed
      CVD is interpreted in the context of autocatalytic kinetic models as a special
      processing window in which a sufficiently high flux of feedstock gas drives the
      nucleation and rapid growth phases of a catalyst nanoparticle ensemble to occur
      within the temporal period of the gas pulse, but without inducing growth
      termination.

PMID- 22419544
TI  - Concise review: Immune recognition of induced pluripotent stem cells.
AB  - Autologous-induced pluripotent stem cells (iPSCs) may eventually be used in cell
      replacement therapies to treat a wide range of diseases and have been touted as a
      solution to the vexing problem of immune rejection in this context. Emerging
      evidence suggests, however, that ostensibly histocompatible iPSCs may be rejected
      following transplantation. Here, we review the mechanisms that contribute to
      immunogenicity in iPSCs and forward approaches to permit their acceptance in
      potential cell replacement therapies.

PMID- 22419545
TI  - A density functional theory study on the effect of zero-point energy corrections
      on the methanation profile on Fe(100).
AB  - The thermodynamics and kinetics of the surface hydrogenation of adsorbed atomic
      carbon to methane, following the reaction sequence C+4H(-->/<--)CH+3H(-->/<-
      )CH(2)+2H(-->/<--)CH(3)+H(-->/<--)CH(4), are studied on Fe(100) by means of
      density functional theory. An assessment is made on whether the adsorption
      energies and overall energy profile are affected when zero-point energy (ZPE)
      corrections are included. The C, CH and CH(2) species are most stable at the
      fourfold hollow site, while CH(3) prefers the twofold bridge site. Atomic
      hydrogen is adsorbed at both the twofold bridge and fourfold hollow sites.
      Methane is physisorbed on the surface and shows neither orientation nor site
      preference. It is easily desorbed to the gas phase once formed. The incorporation
      of ZPE corrections has a very slight, if any, effect on the adsorption energies
      and does not alter the trends with regards to the most stable adsorption sites.
      The successive addition of hydrogen to atomic carbon is endothermic up to the
      addition of the third hydrogen atom resulting in the methyl species, but
      exothermic in the final hydrogenation step, which leads to methane. The overall
      methanation reaction is endothermic when starting from atomic carbon and hydrogen
      on the surface. Zero-point energy corrections are rarely provided in the
      literature. Since they are derived from C-H bonds with characteristic vibrations
      on the order of 2500-3000 cm(-1), the equivalent ZPE of 1/2 hnu is on the order
      of 0.2-0.3 eV and its effect on adsorption energy can in principle be
      significant. Particularly in reactions between CH(x) and H, the ZPE correction is
      expected to be significant, as additional C-H bonds are formed. In this instance,
      the methanation reaction energy of +0.77 eV increased to +1.45 eV with the
      inclusion of ZPE corrections, that is, less favourable. Therefore, it is crucial
      to include ZPE corrections when reporting reactions involving hydrogen-containing
      species.

PMID- 22419546
TI  - Factors associated with breast cancer worry 3 years after completion of adjuvant
      treatment.
AB  - OBJECTIVE: Although many survivors continue to worry about cancer years after
      completing treatment, little is known about factors associated with cancer worry.
      This study examined associations between breast cancer worry and demographic and
      clinical variables, as well as fatigue, symptom burden, and risk perception in a
      sample of breast cancer survivors 3 years post-adjuvant treatment. We
      hypothesized that after controlling for demographic and treatment factors, a
      significant proportion of variance in cancer worry would be explained by greater
      fatigue severity, more symptom burden, and greater perceived risk of recurrence.
      METHODS: Stage 0-II breast cancer patients (N = 202) completed measures of risk
      perception, cancer worry (modified Lerman's Cancer Worry Scale), symptom burden
      (Memorial Symptom Assessment Scale), and fatigue severity (Fatigue Symptom
      Inventory) 3 years after completing adjuvant treatment. Multiple regression
      analyses were used to determine the proportion of variance in cancer worry
      accounted for by fatigue, symptom burden, and risk perception after controlling
      for demographic and clinical variables. RESULTS: Age, fatigue, symptom burden,
      and risk perception each explained a significant proportion of variance in cancer
      worry (p < 0.05). Fatigue, symptom burden, and risk perception together accounted
      for 27% of the variance in cancer worry after controlling for demographic and
      clinical factors (p < 0.01). CONCLUSIONS: The hypothesis was supported that
      fatigue, symptom burden, and risk perception are associated with cancer worry
      among breast cancer survivors. It is possible that lingering fatigue and other
      symptoms may remind breast cancer survivors of their disease.

PMID- 22419547
TI  - Vitamin K, an emerging nutrient in brain function.
AB  - Historically discovered for its role in blood coagulation, there is now
      convincing evidence that vitamin K has important actions in the nervous system.
      As a unique cofactor to the gamma-glutamyl carboxylase enzyme, vitamin K
      contributes to the biological activation of proteins Gas6 and protein S, ligands
      for the receptor tyrosine kinases of the TAM family (Tyro3, Axl, and Mer).
      Functionally, Gas6 has been involved in a wide range of cellular processes that
      include cell growth, survival, and apoptosis. In brain, vitamin K also
      participates in the synthesis of sphingolipids, an important class of lipids
      present in high concentrations in brain cell membranes. In addition to their
      structural role, sphingolipids are now known to partake in important cellular
      events such as proliferation, differentiation, senescence and cell-cell
      interactions. In recent years, studies have linked alterations in sphingolipid
      metabolism to age-related cognitive decline and neurodegenerative diseases such
      as Alzheimer's disease (AD). Emerging data also point to unique actions of the K
      vitamer menaquinone-4 (MK-4) against oxidative stress and inflammation. Finally,
      there is now data to suggest that vitamin K has the potential to influence
      psychomotor behavior and cognition. This review presents an overview of what is
      known of the role of vitamin K in brain function.

PMID- 22419548
TI  - Distribution of metal released from cobalt-chromium alloy orthopaedic wear
      particles implanted into air pouches in mice.
AB  - Metal-on-metal hip replacement implants generate wear debris and release ions
      both locally and systemically in patients. To investigate dissemination of metal,
      we determined blood and organ levels of cobalt (Co), chromium (Cr), and
      molybdenum (Mo) following the implantation of Co-Cr alloy wear debris in mice
      using skin pouches as a model system. We observed increased metal levels in blood
      for up to 72 h; the levels of Co were highest and remained elevated for 7 days.
      Co levels were elevated in all organs studied (liver, kidney, spleen, lung,
      heart, brain, and testes), with the peak at 48 h; highest levels were measured in
      liver and kidney (838.9 +/- 223.7 ng/g in liver, and 938.8 +/- 131.6 ng/g in
      kidney). Organ Cr levels were considerably lower than Co levels, for example, Cr
      in kidney was 117.2 +/- 12.6 ng/g tissue at 48 h. Co is more mobile than Cr,
      reaching higher levels at earlier time points. This could be due to local tissue
      binding of Cr. Exposure to Co-Cr particles in vivo altered antioxidant enzyme
      expression and activities. We observed induction of catalase protein in the liver
      and glutathione reductase (GR) and peroxidase (GPx) proteins in the spleen.
      Activities of catalase and GPx in the liver were significantly increased while
      that of GR was decreased in the kidney. Organs of mice with Co-Cr particle
      implantation were exposed to increased metal levels capable of inducing reactive
      oxygen species scavenging enzymes, suggesting the tissue may be subjected to
      oxidative stress; however, the overall antioxidant defence system was not
      markedly disturbed.

PMID- 22419549
TI  - Insights on the acetylated NF-kappaB transcription factor complex with DNA from
      molecular dynamics simulations.
AB  - The nuclear factor-kappaB (NF-kappaB) is a DNA sequence-specific regulator of
      many important biological processes, whose activity is modulated by enzymatic
      acetylation. In one of the best functionally characterized NF-kappaB complexes,
      the p50/p65 heterodimer, acetylation of K221 at p65 causes a decrease of DNA
      dissociation rate, whilst the acetylation of K122 and K123, also at p65, markedly
      decreases the binding affinity for DNA. By means of molecular dynamics
      simulations based on the X-ray structure of the p50/p65 complex with DNA, we
      provide insights on the structural determinants of the acetylated complexes in
      aqueous solution. Lysine acetylation involves the loss of favorable electrostatic
      interactions between DNA and NF-kappaB, which is partially compensated by the
      reduction of the desolvation free-energy of the two binding partners. Acetylation
      at both positions K122 and K123 is associated with a decrease of the
      electrostatic potential at the p65/DNA interface, which is only partially
      counterbalanced by an increase of the local Na(+) concentration. It induces the
      disruption of base-specific and nonspecific interactions between DNA and NF
      kappaB and it is consistent with the observed decrease of binding affinity. In
      contrast, acetylation at position K221 results in the loss of nonspecific protein
      DNA interactions, but the DNA recognition sites are not affected. In addition,
      the loss of protein-DNA interactions is likely to be counterbalanced by an
      increase of the configurational entropy of the complex, which provides, at a
      speculative level, a justification for the observed decrease of NF-kappaB/DNA
      dissociation rate.

PMID- 22419550
TI  - TROP2 is epigenetically inactivated and modulates IGF-1R signalling in lung
      adenocarcinoma.
AB  - Trop-2, a cell surface glycoprotein, contains both extracellular epidermal growth
      factor-like and thyroglobulin type-1 repeat domains. Low TROP2 expression was
      observed in lung adenocarcinoma tissues as compared with their normal
      counterparts. The lack of expression could be due to either the loss of
      heterozygosity (LOH) or hypermethylation of the CpG island DNA of TROP2 upstream
      promoter region as confirmed by bisulphite sequencing and methylation-specific
      (MS) polymerase chain reaction (PCR). 5-Aza-2'-deoxycytidine treatment on lung
      cancer cell (CL) lines, CL1-5 and A549, reversed the hypermethylation status and
      elevated both TROP2 mRNA and protein expression levels. Enforced expression of
      TROP2 in the lung CL line H1299 reduced AKT as well as ERK activation and
      suppressed cell proliferation and colony formation. Conversely, silencing TROP2
      with shRNA transfection in the less efficiently tumour-forming cell line H322M
      enhanced AKT activation and increased tumour growth. Trop-2 could attenuate IGF
      1R signalling-mediated AKT/beta-catenin and ERK activation through a direct
      binding of IGF1. In conclusion, inactivation of TROP2 due to LOH or by DNA
      methylation may play an important role in lung cancer tumourigenicity through
      losing its suppressive effect on IGF-1R signalling and tumour growth.

PMID- 22419555
TI  - Rapid-exchange guide catheter extension for extending the reach of an AL3 guide
      in a patient with a long, dilated ascending aorta.
AB  - We describe the use of a rapid-exchange style guide catheter extension to
      facilitate diagnostic coronary angiography in a patient with a long, dilated
      ascending aorta. The guide catheter extension is an easy to use device that can
      extend the reach of 110 cm catheters. There are several advantages to this
      "mother and child" guide catheter extension over the traditional telescoping
      catheter approach.

PMID- 22419556
TI  - Treatment of a mouse model of spinal cord injury by transplantation of human
      induced pluripotent stem cell-derived long-term self-renewing neuroepithelial
      like stem cells.
AB  - Because of their ability to self-renew, to differentiate into multiple lineages,
      and to migrate toward a damaged site, neural stem cells (NSCs), which can be
      derived from various sources such as fetal tissues and embryonic stem cells, are
      currently considered to be promising components of cell replacement strategies
      aimed at treating injuries of the central nervous system, including the spinal
      cord. Despite their efficiency in promoting functional recovery, these NSCs are
      not homogeneous and possess variable characteristics depending on their
      derivation protocols. The advent of induced pluripotent stem (iPS) cells has
      provided new prospects for regenerative medicine. We used a recently developed
      robust and stable protocol for the generation of long-term, self-renewing,
      neuroepithelial-like stem cells from human iPS cells (hiPS-lt-NES cells), which
      can provide a homogeneous and well-defined population of NSCs for standardized
      analysis. Here, we show that transplanted hiPS-lt-NES cells differentiate into
      neural lineages in the mouse model of spinal cord injury (SCI) and promote
      functional recovery of hind limb motor function. Furthermore, using two different
      neuronal tracers and ablation of the transplanted cells, we revealed that
      transplanted hiPS-lt-NES cell-derived neurons, together with the surviving
      endogenous neurons, contributed to restored motor function. Both types of neurons
      reconstructed the corticospinal tract by forming synaptic connections and
      integrating neuronal circuits. Our findings indicate that hiPS-lt-NES
      transplantation represents a promising avenue for effective cell-based treatment
      of SCI.

PMID- 22419557
TI  - Band-edge electronic structure of beta-In2S3: the role of s or p orbitals of
      atoms at different lattice positions.
AB  - As a promising solar-energy material, the electronic structure and optical
      properties of Beta phase indium sulfide (beta-In(2)S(3)) are still not thoroughly
      understood. This paper devotes to solve these issues using density functional
      theory calculations. beta-In(2)S(3) is found to be an indirect band gap
      semiconductor. The roles of its atoms at different lattice positions are not
      exactly identical because of the unique crystal structure. Additonally, a
      significant phenomenon of optical anisotropy was observed near the absorption
      edge. Owing to the low coordination numbers of the In3 and S2 atoms, the
      corresponding In3-5s states and S2-3p states are crucial for the composition of
      the band-edge electronic structure, leading to special optical properties and
      excellent optoelectronic performances.

PMID- 22419558
TI  - B-vitamins for neuroprotection: narrowing the evidence gap.
AB  - A compelling and extensive epidemiological literature documents the strong
      association of inadequate status of folate, vitamin B12, and to a lesser degree
      vitamin B6, with increased risk of neurodegenerative and cerebrovascular disease.
      Mildly elevated plasma total homocysteine, which is biochemically related to low
      status of these B-vitamins, is similarly associated with increased risk for these
      conditions. This, together with experimental data showing that experimental B
      vitamin deficiency and/or hyperhomocysteinemia can cause a variety of
      neurological and vascular deficits in animals, has provided the evidence base and
      motivation for a growing number of large randomized, double-blind clinical trials
      aimed at determining the efficacy and safety of B-vitamin supplementation for
      preserving cognitive function in older adults. Despite some encouraging trials
      showing benefit of B-vitamins for slowing brain atrophy and cognitive decline,
      the majority of these studies have not demonstrated that B-vitamin
      supplementation has protective or therapeutic cognitive benefit. There are many
      possible explanations for the inconsistency between the clinical trials and for
      the discrepancy between their findings and the predictions of the epidemiological
      evidence. Among these are the possibility of inadequate hypotheses guiding the
      trials, design limitations of the individual trials, and inherent limitations of
      nutritional randomized clinical trials. Resolving these issues will be crucial
      for designing definitive trials and ultimately for guiding nutritional
      interventions for cognitive protection.

PMID- 22419559
TI  - Synthesis and characterization of hydroxyapatite with different crystallinity:
      effects on protein adsorption and release.
AB  - Increasing demand exists for the development of a tissue-engineered alternative
      in the repair of nonunion and critical-sized bone defects. The delivery of
      osteoinductive proteins, such as bone morphogenetic proteins (BMPs), to replicate
      physiological bone-healing process appears a logical and promising option, but is
      currently limited in its clinical application due to lack of a suitable drug
      carrier. The study aimed to investigate the effects of the crystallinity of
      hydroxyapatite (HA) drug carrier on adsorption of proteins onto and their release
      from the carrier. HA samples with different crystallinities were synthesized
      under controlled conditions, that is, pH, temperature, and maturation time, and
      characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM),
      and surface area analyzer. Results demonstrated that both bovine serum albumin
      (BSA) and cytochrome C had a greater tendency to bind onto amorphous calcium
      phosphate (ACP) than crystalline HA, and the adsorption rate was correlated
      oppositely with the HA crystallinity. For both BSA and cytochrome C, the release
      kinetics of protein from HA depended on the crystallinity of HA, in which ACP had
      the highest release rate at 74%, whereas only 15% of proteins were released from
      the highly crystalline HA over a 14-day period. Burst release within 12 h of
      incubation was observed for all groups.

PMID- 22419560
TI  - Interpreting differences in patterns of supportive care needs between patients
      with breast cancer and patients with colorectal cancer.
AB  - BACKGROUND: Understanding cancer patients' supportive care needs can help
      optimize health-care systems and inform services development. We therefore
      examined the prevalence of supportive care needs in Chinese breast (BC) and
      colorectal cancer (CRC) patients to identify prevalence and correlates of unmet
      needs. METHODS: We assessed supportive care needs (Supportive Care Needs Survey
      Short Form), psychological distress (the Hospital Anxiety and Depression Scale),
      symptom distress (The Memorial Symptom Assessment Scale-Short Form), and
      satisfaction with care (Patient Satisfaction Questionnaire) among 210 Chinese BC
      (97) or CRC (104) outpatient clinic attendees. RESULTS: Breast cancer patients
      (89.7%) reported more unmet needs (chi(2)  = 4.409, p = 0.027), but both CRC and
      BC samples ranked unmet needs prevalence similarly, with health system and
      information needs reported as the most common. Younger patients reported higher
      health system and information and sexuality needs. After multivariate adjustment,
      the strength of unmet needs did not differ by cancer type. Unmet psychological,
      physical and daily living, and sexuality needs were positively associated with
      greater symptom distress. Greater health system information needs were associated
      with high global distress and low depression scores, whereas greater
      psychological needs were associated with higher anxiety scores. CONCLUSIONS: Hong
      Kong Chinese BC and CRC patients strongly prioritized needs related to health
      systems and information provision. Symptoms and psychological distress were
      associated with unmet needs, reflecting a service shortfall in symptom
      management. Improving care provision by optimizing communication and clinic
      organization can better prepare cancer patients for their rehabilitation and
      improve symptom control.

PMID- 22419561
TI  - Aquaporin-4 regulates extracellular space volume dynamics during high-frequency
      synaptic stimulation: a gene deletion study in mouse hippocampus.
AB  - Little is known about the physiological roles of aquaporin-4 (AQP4) in the
      central nervous system. AQP4 water channels are concentrated in endfeet membranes
      of astrocytes but also localize to the fine astrocytic processes that abut
      central synapses. Based on its pattern of expression, we predicted that AQP4
      could be involved in controlling water fluxes and changes in extracellular space
      (ECS) volume that are associated with activation of excitatory pathways. Here, we
      show that deletion of Aqp4 accentuated the shrinkage of the ECS that occurred in
      the mouse hippocampal CA1 region during activation of Schaffer
      collateral/commissural fibers. This effect was found in the stratum radiatum
      (where perisynaptic astrocytic processes abound) but not in the pyramidal cell
      layer (where astrocytic processes constitute but a minor volume fraction). For
      both genotypes the ECS shrinkage was most pronounced in the pyramidal cell layer.
      Our data attribute a physiological role to AQP4 and indicate that this water
      channel regulates extracellular volume dynamics in the mammalian brain.

PMID- 22419562
TI  - Radial artery access technique evaluation trial: randomized comparison of
      Seldinger versus modified Seldinger technique for arterial access for transradial
      catheterization.
AB  - BACKGROUND: Radial artery access for transradial catheterization is obtained
      using either Seldinger or modified Seldinger technique. There is no comparative
      evaluation of the safety and benefits of these two techniques. METHODS: Four
      hundred twelve patients undergoing transradial catheterization were randomized to
      group I (n = 210) Seldinger technique, and group II (n = 202) modified Seldinger
      technique. Demographic and procedural data were collected at the time of the
      procedure. Data on hematoma and radial artery occlusion (RAO) were recorded at 24
      hr and 30 days after the procedure. RESULTS: Age, gender, weight, height, and
      history of diabetes mellitus were comparable between groups I and II. Access time
      (78.3 +/- 37.7 sec vs. 134.2 +/- 87.5 sec, P < 0.001), procedure time (17.1 +/-
      6.4 min vs. 19.3 +/- 7.1 min, P < 0.01), number of attempts to get access (1.7 +/
      0.8 vs. 2.2 +/- 0.8, P < 0.001), were significantly different favoring group I.
      Access was obtained at first attempt in 53% of patients in group I compared with
      16% in group II (P < 0.001). Change in technique (crossover) was required in
      10.8% of group II patients, compared with no crossover in group I (P < 0.0001).
      Incidence of hematoma (0.5% vs. 1.5%, P > 0.2) and 30-day RAO (4.3% vs. 3.9 %, P
      > 0.5) was similar between groups I and II. CONCLUSIONS: Seldinger technique is a
      faster and more predictable radial artery access technique compared with modified
      Seldinger technique with no increase in bleeding or RAO.

PMID- 22419563
TI  - Antibody detection of translocations in Ewing sarcoma.
AB  - The detection of chromosomal translocations has important implications in the
      diagnosis, prognosis and treatment of patients with cancer. Current approaches to
      translocation detection have significant shortcomings, including limited
      sensitivity and/or specificity, and difficulty in application to formalin-fixed
      paraffin-embedded (FFPE) clinical samples. We developed a new approach called
      antibody detection of translocations (ADOT) that avoids the shortcomings of
      current techniques. ADOT combines a transcriptional microarray-based approach
      with a novel antibody-based detection method. ADOT allows for the accurate and
      sensitive identification of translocations and provides exon-level information
      about the fusion transcript. ADOT can detect translocations in poor-quality
      unprocessed total ribonucleic acid (RNA). Furthermore, the technique is readily
      generalizable to detect any potential fusion transcript, including previously
      undescribed fusions. We demonstrate the feasibility of ADOT by examples in which
      both known and unknown Ewing sarcoma translocations are identified from cell
      lines, tumour xenografts and FFPE primary tumours. These results demonstrate that
      ADOT may be an effective approach for translocation analysis in clinical
      specimens with significant RNA degradation and may offer a novel diagnostic tool
      for translocation-based cancers.

PMID- 22419564
TI  - Biomarker dynamics: estimating infection rates from serological data.
AB  - The marginal distribution of serum antibody titres in a cross-sectional
      population sample can be expressed as a function of the infection rate, taking
      into account heterogeneity in peak levels and decay rates. This marginal model
      allows estimation of incidences, as well as simple tests for homogeneity across
      age, gender or geographic strata, using likelihood ratio tests. An example is
      given using Campylobacter serum antibody data. Using a hierarchical dynamic model
      to analyse data from a follow-up study in patients with symptomatic Campylobacter
      infection, we show that the serum antibody response consists of a rapid increase
      to peak levels followed by a slow decline with a geometric mean halftime of 1.4,
      0.6 and 0.3 years for IgG, IgM and IgA, respectively. Antibody peak levels and
      decay rates were highly variable among subjects. Incidence estimates are
      consistent among different antibody classes (IgG, IgM and IgA). High
      seroconversion rates indicate that Campylobacter infection is a frequent event,
      occurring approximately once every year in any adult person, in the Netherlands,
      supporting the conclusion that a small fraction of infections leads to symptoms
      severe enough for notification.

PMID- 22419565
TI  - A psychometric evaluation of an English version of the Utrecht Coping List.
AB  - INTRODUCTION AND AIMS: Although coping styles in individuals with eating
      disorders have received increased research interest in recent years, there
      remains a lack of brief, self-report measures that can reliably measure coping.
      This study developed an English version of the Utrecht Coping List (UCL) and
      evaluated its psychometric properties in a UK population. METHOD: This was a
      cross-sectional study. Three hundred and fifteen participants completed the UCL
      and the Coping Orientation to Problems Experienced scale (Carver, Scheier &
      Weintraub, 1989). Of these, 124 completed the UCL again 6 weeks later. RESULTS:
      The UCL demonstrated strong internal consistency. Five of the seven subscales had
      good test-retest reliability. With the exception of the expression of emotion
      subscale in men, concurrent validity with the Coping Orientation to Problems
      Experienced subscales was good. DISCUSSION: Although its use with men requires
      further investigation, this translated version of the UCL represents a reliable
      and valid measure of coping in women.

PMID- 22419566
TI  - Reversible reflection color-control in smectic liquid crystal switched by photo
      isomerization of azobenzene.
AB  - Through the looking glass: A reflection color transition is demonstrated in a
      smectic liquid crystal doped with a photochromic azobenzene and a chiral agent
      with high helical twisting power. The reflection color can be switched reversibly
      due to the isomerization of azobenzene upon UV/visible irradiation.

PMID- 22419567
TI  - Retinoids for treatment of Alzheimer's disease.
AB  - Retinoids are Vitamin A derivatives involved in cellular regulatory processes
      including cell differentiation, neurite outgrowth and defense against oxidative
      stress. Retinoids may also influence Amyloid beta processing upregulation of
      alpha secretase via ADAM10. Vitamin A and other retinoids also directly inhibit
      formation of Amyloid fibrils in vivo. These properties of retinoids are relevant
      to theories of Alzheimer's disease pathogenesis. Retinoids are already used in
      treatment of acne vulgaris, psoriasis, neuroblastoma and acute promyelocytic
      leukemia. Clinical studies involving in cognitively impaired older adults with
      Alzheimer's disease are beginning with a variety of retinoids. These studies need
      to address safety issues of retinoids in older populations, and hold hope for
      demonstrating efficacy in translating these basic mechanisms to treatment of a
      widespread dementing illness.

PMID- 22419568
TI  - Effect of increased strut porosity of calcium phosphate bone graft substitute
      biomaterials on osteoinduction.
AB  - The effect of increasing strut porosity on the osteoinductivity of porous calcium
      phosphate (CaP) and silicate-substituted calcium phosphate (SiCaP) bone
      substitute materials was investigated in an ovine ectopic model. One to two
      millimeter-sized granules or block implants with strut porosities of 10, 20, or
      30% were inserted into the left and right paraspinalis muscle. At 12 weeks,
      histological sections were prepared through the center of each implant and bone
      contact, bone area and implant area quantified. Backscattered scanning electron
      microscopy (bSEM) was used to visualize bone within small pores in the struts of
      the scaffolds. Increased bone formation was measured in the SiCaP with 30% strut
      porosity (5.482% +/- 1.546%) when compared with the nonsilicate CaP with the same
      morphology (1.160% +/- 0.502%, p = 0.02), indicating that silicate substitution
      may increase osteoinduction. Greater bone formation was seen in scaffolds with
      increased strut porosity. No bone growth was found in any of the SiCaP scaffold
      with 10% porosity. There was no significant difference between block and granule
      specimens. Scanning electron microscopy and EDX in combination with histology
      demonstrated bone formation within pores <5 MUm in size. The use of silicate
      substituted CaP material with increased strut porosity may further augment repair
      and regeneration in bony sites.

PMID- 22419569
TI  - The expression profile of the tumor suppressor gene Lzts1 suggests a role in
      neuronal development.
AB  - BACKGROUND: Neuronal circuit assembly comprises a number of developmental
      processes that ultimately underlie function. Identifying the molecular events
      that dictate these processes can give key insights into how neuronal circuit
      formation is coordinated. To begin to identify such molecular mechanisms, we have
      analysed the expression of a candidate gene of entirely unknown function within
      the nervous system. Here we reveal the spatial and temporal distribution of Lzts1
      in mouse and chick embryonic spinal cord and propose potential biological
      functions. RESULTS: Lzts1 mRNA is transiently expressed at the border of the
      ventricular and mantle zones in subsets of sensory and motor spinal neurons. The
      protein is localized to the cell body, axon, and trailing process of motor,
      commissural, and dorsal root neurons during development. CONCLUSIONS: Taken
      together, the spatial and temporal distribution of Lzts1 is consistent with a
      potential function(s) in cell cycle regulation, axon growth or guidance, and/or
      migration of neurons.

PMID- 22419570
TI  - Identification of 4 novel HLA-B*40:01 restricted minor histocompatibility
      antigens and their potential as targets for graft-versus-leukemia reactivity.
AB  - BACKGROUND: Patients with hematologic malignancies can be successfully treated
      with donor lymphocyte infusion after HLA-matched allogeneic hematopoietic stem
      cell transplantation. The effect of donor lymphocyte infusion is mediated by
      donor T cells recognizing minor histocompatibility antigens. T cells recognizing
      hematopoietic restricted minor histocompatibility antigens may induce selective
      graft-versus-leukemia reactivity, whereas broadly-expressed antigens may be
      targeted in graft-versus-host disease. DESIGN AND METHODS: We analyzed in detail
      CD8(+) T-cell immunity in a patient with relapsed chronic myelogenous leukemia
      who responded to donor lymphocyte infusion with minimal graft-versus-host disease
      of the skin. CD8(+) T-cell clones specific for 4 HLA-B*40:01 restricted minor
      histocompatibility antigens were isolated which were identified by screening a
      plasmid cDNA library and whole genome association scanning. Detailed T-cell
      reactivity and monitoring experiments were performed to estimate the clinical and
      therapeutic relevance of the novel antigens. RESULTS: Three antigens were
      demonstrated to be expressed on primary leukemic cells of various origins as well
      as subtypes of non-malignant hematopoietic cells, whereas one antigen was
      selectively recognized on malignant hematopoietic cells with antigen presenting
      cell phenotype. Skin derived fibroblasts were only recognized after pre-treatment
      with IFN-gamma by two T-cell clones. CONCLUSIONS: Our data show evidence for
      different roles of the HLA-B*40:01 restricted minor histocompatibility antigens
      in the onset and execution of the anti-tumor response. All antigens may have
      contributed to a graft-versus-leukemia effect, and one minor histocompatibility
      antigen (LB-SWAP70-1Q) has specific therapeutic value based on its in vivo
      immunodominance and strong presentation on leukemic cells of various origins, but
      absence of expression on cytokine-treated fibroblasts.

PMID- 22419571
TI  - Endoplasmic reticulum anchored heme-oxygenase 1 faces the cytosol.
AB  - Heme-oxygenase 1 is an endoplasmic reticulum-anchored enzyme that breaks down
      heme into iron, carbon monoxide and biliverdin. Heme is a hydrophobic co-factor
      in many proteins, including hemoglobin. Free heme is highly cytotoxic and,
      therefore, both heme synthesis and breakdown are tightly regulated. During
      turnover of heme proteins, heme is released in the phago-lysosomal compartment or
      the cytosol. The subcellular location of the heme-oxygenase 1 active site has not
      been clarified. Using constructs of heme-oxygenase 1 with fluorescent proteins,
      and the endogenous heme-oxygenase 1 in two variations of protease protection
      assays, we determined that heme-oxygenase 1 is membrane-bound and faces the
      cytosol in non-activated macrophages in vivo. These findings imply that in
      quiescent macrophages, heme breakdown products are generated in the cytosol. This
      facilitates iron recycling to ferroportin for iron export and to ferritin for
      iron storage.

PMID- 22419572
TI  - Variations in non-pharmacological anti-infective measures in childhood leukemia-
      results of an international survey.
AB  - BACKGROUND: Standardization in clinical practice may lead to improved outcomes.
      Unfortunately, little is known about the variability of non-pharmacological anti
      infective measures in children with cancer. DESIGN AND METHODS: A web-based
      survey assessed institutional recommendations regarding restrictions of social
      contacts, pets and food and instructions on wearing face masks in public for
      children with standard- risk acute lymphoblastic leukemia and acute myeloid
      leukemia during intensive chemotherapy. RESULTS: A total of 336 institutions in
      27 countries responded to the survey (range, 1-76 institutions per country;
      overall response rate 61%). Most institutions recommend that patients with acute
      myeloid leukemia avoid indoor public places and daycare, kindergarten and school,
      whereas recommendations for patients with acute lymphoblastic leukemia differ
      considerably by institution. In terms of restrictions related to pets, there was
      a wide variability between institutions for both acute lymphoblastic and acute
      myeloid leukemia patients. Most, but not all institutions do not allow children
      with either acute lymphoblastic or acute myeloid leukemia to eat raw meat, raw
      seafood or unpasteurized milk. Whereas most institutions do not routinely
      recommend that patients with acute lymphoblastic leukemia wear face masks in
      public, advice on this matter varies for patients with acute myeloid leukemia.
      CONCLUSIONS: The survey demonstrates that there is a wide variation in
      recommendations on non-pharmacological anti-infective measures between different
      institutions, countries and continents. This information may be used to encourage
      harmonization of supportive care practices and future clinical trials.

PMID- 22419573
TI  - Characterization of the thrombin generation potential of leukemic and solid tumor
      cells by calibrated automated thrombography.
AB  - BACKGROUND: Thrombin, the final enzyme of blood coagulation, is a multifunctional
      serine protease also involved in the progression of cancer. Tumor cells may
      activate blood coagulation proteases through the expression of procoagulant
      activities. However, specific information about the thrombin generation potential
      of malignant tissues is lacking. In this study we applied a single global
      coagulation test, the calibrated automated thrombogram assay, to characterize the
      specific procoagulant phenotypes of different tumor cells. DESIGN AND METHODS:
      Malignant hematologic cells (i.e. NB4, HEL, and K562) or solid tumor cells (i.e.
      MCF-7 breast cancer and H69 small cell lung cells) were selected for the study.
      The calibrated automated thrombo-gram assay was performed in normal plasma and in
      plasma samples selectively deficient in factor VII, XII, IX or X, in the absence
      or presence of a specific anti-tissue factor antibody. Furthermore, cell tissue
      factor levels were characterized by measuring antigen, activity and mRNA
      expression. RESULTS: In normal plasma, NB4 induced the highest thrombin
      generation, followed by MCF-7, H69, HEL, and K562 cells. The anti-tissue factor
      antibody, as well as deficiencies of factors VII, IX and XII affected the
      thrombin generation potential of malignant cells to different degrees, allowing
      differentiation of the two different pathways of blood clotting activation - by
      tissue factor or contact activation. The thrombin generation capacity of NB4 and
      MCF-7 cells was tissue factor-dependent, as it was highly sensitive to inhibition
      by anti-tissue factor antibody and factor VII deficiency, while the thrombin
      generation capacity of H69, HEL and K562 was contact activation-dependent, as no
      thrombin was generated by these cells in factor XII-deficient plasma.
      CONCLUSIONS: This study demonstrates that the calibrated automated thrombogram
      assay is capable of quantifying, characterizing, and comparing the thrombin
      generation capacity of different tumor cells. This provides a useful tool for
      understanding the key factors determining the global pro-coagulant profile of
      tumors, which is important for addressing specific targeted therapy for the
      prevention of thrombosis and for cancer.

PMID- 22419574
TI  - Identification of a novel HLA-G+ regulatory population in blood: expansion after
      allogeneic transplantation and de novo HLA-G expression at graft-versus-host
      disease sites.
AB  - BACKGROUND: The human leukocyte antigen-G (HLA-G) has been considered to be an
      important tolerogeneic molecule playing an essential role in maternal-fetal
      tolerance, which constitutes the perfect example of successful physiological
      immunotolerance of semi-allografts. In this context, we investigated the putative
      role of this molecule in the allogeneic hematopoietic cell transplantation
      setting. DESIGN AND METHODS: The percentage of HLA-G(+) cells in peripheral blood
      of healthy donors and allo-transplanted patients was evaluated by flow cytometry.
      Their immunoregulatory and tolerogeneic properties were investigated in in vitro
      immunostimulatory and immunosuppression assays. Immunohistochemical analysis for
      HLA-G expression was performed in skin biopsies from allo-transplanted patients
      and correlated with the occurrence of graft-versus-host disease. RESULTS: We
      identified a CD14(+)HLA-G(pos) population with an HLA-DR(low) phenotype and
      decreased in vitro immunostimulatory capacity circulating in peripheral blood of
      healthy individuals. Naturally occurring CD14(+)HLA-G(pos) cells suppressed T
      cell responses and exerted an immunotolerogenic action on T cells by rendering
      them hyporesponsive and immunosuppressive in vitro. After allogeneic
      hematopoietic cell transplantation, HLA-G(pos) cells increase in blood.
      Interestingly, besides an increase in CD14(+)HLA-G(pos) cells, there was also a
      pronounced expansion of CD3(+)HLA-G(pos) cells. Of note, CD3(+)HLA-G(pos) and
      CD14(+)HLA-G(pos) cells from transplanted patients were suppressive in in vitro
      lymphoproliferation assays. Furthermore, we found an upregulation of HLA-G
      expression in skin specimens from transplanted patients that correlated with
      graft-versus-host disease. Inflammatory cells infiltrating the dermis of
      transplanted patients were also HLA-G(pos). CONCLUSIONS: We report the presence
      of naturally occurring HLA-G(pos) monocytic cells with in vitro suppressive
      properties. HLA-G expressing regulatory blood cells were found in increased
      numbers after allogeneic transplantation. Epithelial cells in skin affected by
      graft-versus-host disease revealed elevated HLA-G expression.

PMID- 22419575
TI  - Activation state of platelets in experimental severe hemophilia A.

PMID- 22419576
TI  - Marked upregulation of Survivin and Aurora-B kinase is associated with disease
      progression in the myelodysplastic syndromes.
AB  - BACKGROUND: Myelodysplastic syndromes are a heterogeneous group of clonal
      hematopoietic stem cell disorders characterized by ineffective hematopoiesis.
      Survivin is a member of the inhibitor of apoptosis family and suppresses
      apoptosis. Survivin also functions as a subunit of the chromosomal passenger
      complex for regulating mitosis with Aurora-B. Survivin and Aurora-B play an
      important role in maintaining genome stability. The aim of this study was to
      determine the role of Survivin and Aurora-B kinase in disease progression and
      prognosis of myelodysplastic syndromes. DESIGN AND METHODS: We evaluated the
      expression levels of these two genes in CD34(+) cells prepared from 64 patients
      with myelodysplastic syndrome or leukemic blasts from 50 patients with de novo
      acute myeloid leukemia using quantitative real-time PCR. RESULTS: Survivin and
      Aurora-B expression levels were highly correlated with the type of
      myelodysplastic syndrome, were much higher in refractory anemia with excess
      blasts-1, refractory anemia with excess blasts-2, and secondary acute myeloid
      leukemia following myelodysplastic syndrome than in normal control, and increased
      during disease progression. There was a significant correlation between these
      expression levels and the International Prognostic Scoring System. Interestingly,
      these levels were remarkably higher in patients with secondary acute myeloid
      leukemia following myelodysplastic syndromes than in those with de novo acute
      myeloid leukemia. CONCLUSIONS: This is the first report showing that high levels
      of Survivin and Aurora-B kinase expression in CD34(+) cells are distinctive
      molecular features of high-risk myelodysplastic syndromes and secondary acute
      myeloid leukemia following myelodysplastic syndrome. Marked upregulation of
      Survivin and Aurora-B kinase may contribute to genetic instability and disease
      progression of myelodysplastic syndromes. Our data may explain why patients with
      high-risk myelodysplastic syndromes frequently show complex chromosomal
      abnormality.

PMID- 22419577
TI  - Hematologic responses to deferasirox therapy in transfusion-dependent patients
      with myelodysplastic syndromes.
AB  - BACKGROUND: Reductions in transfusion requirements/improvements in hematologic
      parameters have been associated with iron chelation therapy in transfusion
      dependent patients, including those with myelodysplastic syndromes; data on there
      reductions/improvements have been limited to case reports and small studies.
      DESIGN AND METHODS: To explore this observation in a large population of
      patients, we report a post-hoc analysis evaluating hematologic response to
      deferasirox in a cohort of iron-overloaded patients with myelodysplastic
      syndromes enrolled in the Evaluation of Patients' Iron Chelation with Exjade((r))
      (EPIC) study using International Working Group 2006 criteria. RESULTS: Two
      hundred and forty-seven, 100 and 50 patients without concomitant medication for
      myelodysplastic syndromes were eligible for analysis of erythroid, platelet and
      neutrophil responses, respectively. Erythroid, platelet and neutrophil responses
      were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of the patients
      after a median of 109, 169 and 226 days, respectively. Median serum ferritin
      reductions were greater in hematologic responders compared with non-responders at
      end of study, although these differences were not statistically significant. A
      reduction in labile plasma iron to less than 0.4 MUmol/L was observed from week
      12 onwards; this change did not differ between hematologic responders and non
      responders. CONCLUSIONS: This analysis suggests that deferasirox treatment for up
      to 1 year could lead to improvement in hematologic parameters in some patients
      with myelodysplastic syndromes.

PMID- 22419578
TI  - Experience with pegylated interferon alpha-2a in advanced myeloproliferative
      neoplasms in an international cohort of 118 patients.
AB  - The Philadelphia negative myeloproliferative neoplasms, including polycythemia
      vera, essential thrombocythemia, and myelofibrosis, are associated with
      substantial vascular and transformative complications. Standard therapy for high
      risk disease, particularly in patients that have failed initial therapy, remains
      controversial. Non-pegylated interferon has previously been shown to be effective
      in controlling erythrocytosis, thrombocytosis and thrombotic complications, but
      was found to have poor tolerability and excessive adverse effects. Recently,
      pegylated interferon alpha-2a was introduced and found to be better tolerated and
      less toxic than standard interferon. In addition, in recent phase II trials,
      pegylated interferon alpha-2a therapy was found to induce both hematologic and
      molecular remissions. We retrospectively analyzed 118 myeloproliferative patients
      who underwent pegylated interferon alpha-2a treatment. Responses were evaluated
      by ELN, IWG-MET and EUMNET standardized criteria sets and adverse effects were
      analyzed.

PMID- 22419579
TI  - Selection pressure exerted by imatinib therapy leads to disparate outcomes of
      imatinib discontinuation trials.
AB  - BACKGROUND: Chronic myeloid leukemia is successfully managed by imatinib therapy,
      but the question remains whether treatment must be administered indefinitely.
      Imatinib discontinuation trials have led to two distinct outcomes: about 60% of
      patients experienced disease relapse within 6 months of treatment cessation,
      while the remaining 40% remained disease-free throughout the duration of follow
      up. We aimed to investigate the mechanisms underlying these disparate clinical
      outcomes. DESIGN AND METHODS: We utilized molecular data from the "Stop Imatinib"
      trial together with a mathematical framework of chronic myeloid leukemia, based
      on a four-compartment model that can explain the kinetics of the molecular
      response to imatinib. This approach was complemented by statistical analyses to
      estimate system parameters and investigate whether chronic myeloid leukemia can
      be cured by imatinib therapy alone. RESULTS: We found that there are insufficient
      follow-up data from the "Stop Imatinib" trial in order to conclude whether the
      absence of a relapse signifies cure of the disease. We determined that selection
      of less aggressive leukemic phenotypes by imatinib therapy recapitulates the
      trial outcomes. This postulated mechanism agrees with the observation that most
      patients who have a complete molecular response after discontinuation of imatinib
      continue to harbor minimal residual disease, and might work in concert with other
      factors suppressing leukemic cell expansion when the tumor burden remains low.
      CONCLUSIONS: Our analysis provides evidence for a mechanistic model of chronic
      myeloid leukemia selection by imatinib treatment and suggests that it may not be
      safe to discontinue therapy outside a clinical trial.

PMID- 22419580
TI  - Production of the effector cytokine interleukin-17, rather than interferon-gamma,
      is more strongly associated with autoimmune hemolytic anemia.
AB  - BACKGROUND: Interleukin-17A is the signature cytokine of the Th17 subset and
      drives inflammatory pathology, but its relevance to autoantibody-mediated
      diseases is unclear. Th1 cells secreting interferon-gamma have been implicated in
      autoimmune hemolytic anemia, so the aim was to determine which cytokine is more
      closely associated with disease severity. DESIGN AND METHODS: Interferon-gamma
      and interleukin-17A were measured in the sera of patients with autoimmune
      hemolytic anemia and healthy donors, and in peripheral blood mononuclear cell
      cultures stimulated with autologous red blood cells, or a panel of peptides
      spanning red blood cell autoantigen. RESULTS: Serum interleukin-17A, but not
      interferon-gamma, was significantly raised in patients with autoimmune hemolytic
      anemia (P<0.001), and correlated with the degree of anemia. Interleukin-17A was
      also more prominent in the responses of peripheral blood mononuclear cells from
      patients with autoimmune hemolytic anemia to red blood cells, and, again unlike
      interferon-gamma, significantly associated with more severe anemia (P<0.005).
      There were no interleukin-17A responses to red blood cells by peripheral blood
      mononuclear cells from healthy donors. Specific autoantigenic peptides were
      identified that elicit patients' interleukin-17A responses. CONCLUSIONS:
      Interleukin-17A makes a previously unrecognized contribution to the autoimmune
      response in autoimmune hemolytic anemia, challenging the model that the disease
      is driven primarily by Th1 cells. This raises the possibility that Th17, rather
      than Th1, cells should be the target for therapy.

PMID- 22419582
TI  - Angiographic investigation of the pathophysiology of perioperative myocardial
      infarction.
AB  - BACKGROUND: The study of the pathophysiologic mechanism of perioperative
      myocardial infarctions is limited to two small autopsy studies suggesting a major
      role for plaque rupture and thrombosis. However, the perioperative period is
      characterized by increased cardiac metabolic demand that may lead to infarction
      in patients with otherwise stable obstructive coronary artery disease. The
      purpose of this study is to investigate the pathophysiology of perioperative
      myocardial infarctions. METHODS: Hospital records and coronary angiograms from
      patients from 1998 to 2006 who underwent noncardiac surgery complicated by a
      perioperative myocardial infarction (MI) were reviewed. The culprit lesion was
      identified based on ECG, left ventriculography, and coronary angiography. Degree
      of stenosis, TIMI flow, ACC thrombus grade, calcification score, and lesion
      morphology were evaluated. Based on these criteria, MIs were categorized as
      thrombotic, demand, or nonobstructive. RESULTS: Sixty-six patients (average age,
      71 years and 44% male), 77% of whom underwent an intermediate risk surgery with a
      2% perioperative mortality, were identified. The distribution of demand,
      thrombotic, and nonobstructive MI was 55%, 26%, and 19%, respectively. There was
      neither statistical difference in the occurrence of prolonged hypotension or
      tachycardia between groups nor was there any difference in the use of
      antiplatelets, beta-blockers, or statins. CONCLUSION: This study identified
      demand ischemia as the predominant etiology of perioperative MIs in this cohort.
      An improved understanding of the pathophysiologic mechanism of perioperative MIs
      may facilitate the evaluation and management of preoperative patients.

PMID- 22419581
TI  - Highly activated and expanded natural killer cells for multiple myeloma
      immunotherapy.
AB  - BACKGROUND: Patients with gene expression profiling-defined high-risk myeloma in
      relapse have poor outcomes with current therapies. We tested whether natural
      killer cells expanded by co-culture with K562 cells transfected with 41BBL and
      membrane-bound interleukin-15 could kill myeloma cells with a high-risk gene
      expression profile in vitro and in a unique model which recapitulates human
      myeloma. DESIGN AND METHODS: OPM2 and high-risk primary myeloma tumors were grown
      in human fetal bone implanted into non-obese diabetic severe combined
      immunodeficiency mice with a deficient interleukin-2 receptor gamma chain. These
      mice are devoid of endogenous natural killer and T-cell activity and were used to
      determine whether adoptively transferred expanded natural killer cells could
      inhibit myeloma growth and myeloma-associated bone destruction. RESULTS: Natural
      killer cells from healthy donors and myeloma patients expanded a median of 804-
      and 351-fold, respectively, without significant T-cell expansion. Expanded
      natural killer cells killed both allogeneic and autologous primary myeloma cells
      avidly via a perforin-mediated mechanism in which the activating receptor NKG2D,
      natural cytotoxicity receptors, and DNAX-accessory molecule-1 played a central
      role. Adoptive transfer of expanded natural killer cells inhibited the growth of
      established OPM2 and high-risk primary myeloma tumors grown in the murine model.
      The transferred, expanded natural killer cells proliferated in vivo in an
      interleukin-2 dose-dependent fashion, persisted up to 4 weeks, were readily
      detectable in the human bone, inhibited myeloma growth and protected bone from
      myeloma-induced osteolysis. CONCLUSIONS: These studies provide the rationale for
      testing expanded natural killer cells in humans.

PMID- 22419583
TI  - Meeting Report: EMBL Conference - Omics and Personalized Medicine: February 16
      18, 2012, Heidelberg, Germany.
AB  - The first EMBL conference on "Omics and Personalized Medicine", jointly organized
      by Rudi Balling (LCSB, Luxembourg), Leroy Hood, Wolfgang Huber (EMBL, Heidelberg,
      Germany) and Lars Steinmetz (EMBL) addresses the potential and challenges of
      translating systems biology research into the clinic. This meeting report
      provides a highlight of the conference, covering not only the science, but also
      social and legal issues.

PMID- 22419584
TI  - Estimation and variable selection via frailty models with penalized likelihood.
AB  - The penalized likelihood methodology has been consistently demonstrated to be an
      attractive shrinkage and selection method. It does not only automatically and
      consistently select the important variables but also produces estimators that are
      as efficient as the oracle estimator. In this paper, we apply this approach to a
      general likelihood function for data organized in clusters, which corresponds to
      a class of frailty models, which includes the Cox model and the Gamma frailty
      model as special cases. Our aim was to provide practitioners in the medical or
      reliability field with options other than the Gamma frailty model, which has been
      extensively studied because of its mathematical convenience. We illustrate the
      penalized likelihood methodology for frailty models through simulations and real
      data.

PMID- 22419585
TI  - Are auditory and visual processing deficits related to developmental dyslexia?
AB  - The purpose of this study was to examine if children with dyslexia learning to
      read a consistent orthography (Greek) experience auditory and visual processing
      deficits and if these deficits are associated with phonological awareness, rapid
      naming speed and orthographic processing. We administered measures of general
      cognitive ability, phonological awareness, orthographic processing, short-term
      memory, rapid automatized naming, auditory and visual processing, and reading
      fluency to 21 Grade 6 children with dyslexia, 21 chronological age-matched
      controls and 20 Grade 3 reading age-matched controls. The results indicated that
      the children with dyslexia did not experience auditory processing deficits, but
      about half of them showed visual processing deficits. Both orthographic
      processing and rapid automatized naming deficits were associated with dyslexia in
      our sample, but it is less clear that they were associated with visual processing
      deficits.

PMID- 22419587
TI  - Good news for BAMBED readers and authors: Medline, Wiley early view, and author
      services.

PMID- 22419586
TI  - Mitochondrial pharmacology: electron transport chain bypass as strategies to
      treat mitochondrial dysfunction.
AB  - Mitochondrial dysfunction (primary or secondary) is detrimental to intermediary
      metabolism. Therapeutic strategies to treat/prevent mitochondrial dysfunction
      could be valuable for managing metabolic and age-related disorders. Here, we
      review strategies proposed to treat mitochondrial impairment. We then concentrate
      on redox-active agents, with mild-redox potential, who shuttle electrons among
      specific cytosolic or mitochondrial redox-centers. We propose that specific redox
      agents with mild redox potential (-0.1 V; 0.1 V) improve mitochondrial function
      because they can readily donate or accept electrons in biological systems, thus
      they enhance metabolic activity and prevent reactive oxygen species (ROS)
      production. These agents are likely to lack toxic effects because they lack the
      risk of inhibiting electron transfer in redox centers. This is different from
      redox agents with strong negative (-0.4 V; -0.2 V) or positive (0.2 V; 0.4 V)
      redox potentials who alter the redox status of redox-centers (i.e., become
      permanently reduced or oxidized). This view has been demonstrated by testing the
      effect of several redox active agents on cellular senescence. Methylene blue (MB,
      redox potential ?10 mV) appears to readily cycle between the oxidized and reduced
      forms using specific mitochondrial and cytosolic redox centers. MB is most
      effective in delaying cell senescence and enhancing mitochondrial function in
      vivo and in vitro. Mild-redox agents can alter the biochemical activity of
      specific mitochondrial components, which then in response alters the expression
      of nuclear and mitochondrial genes. We present the concept of mitochondrial
      electron-carrier bypass as a potential result of mild-redox agents, a method to
      prevent ROS production, improve mitochondrial function, and delay cellular aging.
      Thus, mild-redox agents may prevent/delay mitochondria-driven disorders.

PMID- 22419588
TI  - Development of embedded assessments for learning in biotechnology: results and
      design process for dissemination.
AB  - Embedded assessments, tasks within the context of instruction, can serve as
      important tools for improving teaching and learning. In this article, we report
      on the assessment design principles and a nine-step development model that guided
      the construction of innovative embedded assessments. Using multiple sources of
      data-expert reviews, a conceptual test blueprint, student interviews, focus group
      interviews, and student responses to assessments-we were able to analyze the
      extent to which our assessments align with research-based design principles.
      Specifically, our results demonstrate that the assessments: (a) align with
      learning and instructional goals; (b) are cognitively challenging; (c) support
      student learning; and (d) have reduced potential bias. These assessments were
      developed in the context of an introductory biochemistry course for
      nonbiochemistry majors with learning goals in areas of: scientific content, socio
      scientific issues, and evidence-based decision making skills. The assessment
      design principles and development model are generalizable to other science
      disciplines. We discuss how the application of these design principles can
      generate valid and reliable embedded assessments that can be integrated into a
      modern classroom.

PMID- 22419589
TI  - A contemporary, laboratory-intensive course on messenger RNA transcription and
      processing.
AB  - Messenger ribonucleic acid (mRNA) plays a pivotal role in the central dogma of
      molecular biology. Importantly, molecular events occurring during and after mRNA
      synthesis have the potential to create multiple proteins from one gene, leading
      to some of the remarkable protein diversity that genomes hold. The North Carolina
      State University Biotechnology Program developed and implemented a new,
      laboratory-intensive course to provide students with a contemporary view of mRNA
      entitled "mRNA: Transcription and Processing." This course, offered at both the
      undergraduate and graduate levels, aimed to introduce students to the many
      functions of RNA, with an emphasis on mRNA. In addition to fundamental aspects of
      these processes, students were exposed to cutting-edge techniques used to analyze
      mRNA in both lecture and laboratory components. We evaluated this course over two
      semesters and found that learning outcomes were met by both undergraduate and
      graduate students, based on assessments such as laboratory reports, pre-lab
      assignments, a final exam, and successful results in the laboratory. We also
      examined student perceptions through anonymous surveys, where students reported
      gains in confidence in both conceptual knowledge and technical skill after
      completing this course.

PMID- 22419590
TI  - Using graph-based assessments within socratic tutorials to reveal and refine
      students' analytical thinking about molecular networks.
AB  - Biological systems, from the molecular to the ecological, involve dynamic
      interaction networks. To examine student thinking about networks we used
      graphical responses, since they are easier to evaluate for implied, but
      unarticulated assumptions. Senior college level molecular biology students were
      presented with simple molecular level scenarios; surprisingly, most students
      failed to articulate the basic assumptions needed to generate reasonable
      graphical representations; their graphs often contradicted their explicit
      assumptions. We then developed a tiered Socratic tutorial based on leading
      questions designed to provoke metacognitive reflection. The activity is
      characterized by leading questions (prompts) designed to provoke meta-cognitive
      reflection. When applied in a group or individual setting, there was clear
      improvement in targeted areas. Our results highlight the promise of using
      graphical responses and Socratic prompts in a tutorial context as both a
      formative assessment for students and an informative feedback system for
      instructors, in part because graphical responses are relatively easy to evaluate
      for implied, but unarticulated assumptions.

PMID- 22419591
TI  - PCR analysis of expR gene regulating biosynthesis of exopolysaccharides in
      Sinorhizobium meliloti.
AB  - Exopolysaccharide (EPS) production by the rhizobacterium Sinorhizobium meliloti
      is essential for root nodule formation on its legume host (alfalfa), and for
      establishment of a nitrogen-fixing symbiosis between the two partners. Production
      of EPS II (galactoglucan) by certain S. meliloti strains results in a mucoid
      colony phenotype. Other strains that are unable to produce EPS II display a dry
      phenotype, due to the presence of an insertion element in the gene expR, a key
      regulator involved in many important cellular processes, including production of
      low-molecular-weight EPS II. We describe a series of three programmed
      undergraduate biochemistry laboratory classes teaching PCR and electrophoresis
      procedures to detect non-functional expR loci in S. meliloti.

PMID- 22419592
TI  - Molecular diagnostic analysis of outbreak scenarios.
AB  - In the current laboratory assignment, technical aspects of the polymerase chain
      reaction (PCR) are integrated in the context of six different bacterial outbreak
      scenarios. The "Enterobacterial Repetitive Intergenic Consensus Sequence" (ERIC)
      PCR was used to analyze different outbreak scenarios. First, groups of 2-4
      students determined optimal ERIC-PCR conditions to validate the protocol and
      subsequently applied ERIC-PCR to identify genetic relatedness among bacterial
      strains. Based on these genetic fingerprints, students selected the outbreak
      cases from the patient samples and assessed the risk factors for the outbreak
      scenario. Finally, students presented their findings during a classroom
      presentation. The results indicated that the assignment successfully facilitated
      student learning on the technical aspects of (ERIC) PCR and clearly demonstrated
      the practical application of PCR in a clinical diagnostic setting. Additionally,
      the assignment was highly appreciated by the students.

PMID- 22419593
TI  - Partial characterization of a novel amphibian hemoglobin as a model for graduate
      student investigation on peptide chemistry, mass spectrometry, and atomic force
      microscopy.
AB  - Graduate students in chemistry, and in biological and biomedical fields must
      learn the fundamentals and practices of peptide and protein chemistry as early as
      possible. A project-oriented approach was conducted by first-year M.Sc and Ph.D
      students in biological sciences. A blind glass slide containing a cellular smear
      and an aqueous cellular extract were offered to the students. Qualitative and
      quantitative cell morphological parameters were analyzed by atomic force
      microscopy. The fractionation of the aqueous extract was conducted by reversed
      phase chromatography followed by analysis of the isolated and partially purified
      proteins and peptides by mass spectrometry (MS). The proteins were treated by
      peptidases and the obtained peptide fragments were sequenced by de novo MS/MS,
      together with peptides already present in the extract. The most abundant protein
      fractions were identified as the alpha and beta chains of hemoglobin from an
      amphibian of the Leptodactylus genera. Two of the peptides sequenced by the
      students were synthesized by the solid-phase methodology, one of those being
      obtained by the split-and-pool library synthesis method. Thus, the students were
      able to learn some advanced principles and practices of protein chemistry and
      bionanotechnology in a 6-weeks project-oriented approach.

PMID- 22419594
TI  - Using biocatalysis to integrate organic chemistry into a molecular biology
      laboratory course.
AB  - Current cutting-edge biomedical investigation requires that the researcher have
      an operational understanding of several diverse disciplines. Biocatalysis is a
      field of science that operates at the crossroads of organic chemistry,
      biochemistry, microbiology, and molecular biology, and provides an excellent
      model for interdisciplinary research. We have developed an inquiry-based module
      that uses the mutagenesis of the yeast reductase, YDL124w, to study the
      bioorganic synthesis of the taxol side-chain, a pharmacologically important
      molecule. Using related structures, students identify regions they think will
      affect enzyme stereoselective, design and generate site-specific mutants, and
      then characterize the effect of these changes on enzyme activity. This laboratory
      activity gives our students experience, working in a scientific discipline
      outside of biology and exposes them to techniques and equipment they do not
      normally work with in a molecular biology course. These inter-disciplinary
      experiences not only show the relevance of other sciences to biology, but also
      give our students the ability to communicate more effectively with scientists
      outside their discipline.

PMID- 22419595
TI  - Visualizing the perception filter and breaching it with active-learning
      strategies.

PMID- 22419596
TI  - Problem-solving test: the mechanism of transcription termination by the Rho
      factor.
AB  - Terms to be familiar with before starting to solve the test: Transcription
      termination, recombinant plasmid, annealing, molecular hybridization, heat
      denaturation, agarose gel electrophoresis, autoradiography, RNA polymerase, and
      antiparallel orientation.

PMID- 22419597
TI  - Commentary: iBooks packaging textbooks for the iPad.

PMID- 22419598
TI  - Acetylcholinesterase: substrate traffic and inhibition.

PMID- 22419599
TI  - Reintroducing photosynthesis.
AB  - This article reports on conceptual difficulties related to photosynthesis and
      respiratory metabolism of a Plant Physiology course for undergraduate students
      that could hinder their better learning of metabolic processes. A survey of
      results obtained in this area during the last 10 academic years was performed, as
      well as a specific test, aimed to find out prior conceptual schemes in the
      students. The test included only basic, general questions on plant metabolism,
      and was passed on the first day of the course. Scores obtained by different
      groups of students were compared. Survey of students' performance in previous
      years shows that questions on plant metabolism result in significantly lower
      number of correct answers than for the rest of questions, despite reiteration of
      its teaching in prior educational levels. Some areas such as respiration or light
      independent reactions of photosynthesis, as well as concepts and terminology
      related to electrochemistry, seem to be particularly difficult. The specific test
      also shows differences among the different groups of students included in this
      investigation. Our results point out that reiteration of a particular subject in
      the curricula at different educational levels does not result in a coherent
      enough conceptual scheme in the students. To help students in this task, it is
      recommended to teach the general processes also in advanced courses in which
      these processes are taught in great detail. In this way, settlement of the
      appropriate conceptual scheme may be reinforced.

PMID- 22419601
TI  - Botulinum toxin injections into salivary glands to decrease oral secretions in
      CHARGE syndrome: prospective case study.
AB  - CHARGE syndrome is a genetic disorder caused by a mutation in the CHD7 gene on
      chromosome 8. Major clinical diagnostic criteria for this heterogeneous disorder
      include ocular coloboma, choanal atresia/stenosis, characteristic external and
      internal ear abnormalities, and cranial nerve abnormalities. Patients with CHARGE
      syndrome often have dysphagia and are at high risk for aspiration of both upper
      and lower gastrointestinal secretions. The following case-report describes the
      use of Botulinum toxin A (Botox) to reduce excess salivary secretions in a
      ventilator dependant infant who would have required a tracheotomy. Thereafter,
      Botox was used regularly (4-5 months) to decrease the salivary secretions. This
      case-report is unique in that it describes the intermittent and prospective use
      of Botox to reduce excess salivary secretions and prevent the resulting
      aspiration-related complications in an infant with CHARGE syndrome.

PMID- 22419602
TI  - Persistence of resinous cement residues in dentin treated with different chemical
      removal protocols.
AB  - The aim of this study was to evaluate the persistence of resin cement residues
      after dentin surface cleaning with different alcohol-based solutions or an
      essential oil (eucalyptol). Forty bovine teeth were sectioned in order to expose
      pulp chamber dentin to be washed with 1.0 mL of 2.5% sodium hypochlorite (NaOCl),
      followed by 0.1 mL of 17% EDTA application for 3 min, and final irrigation with
      2.5% NaOCl. The specimens were air dried and resin-based cement was rubbed onto
      the dentine surface with a microbrush applicator. After 15 min, the surface was
      scrubbed with a cotton pellet and moistened with different dentin cleaning
      solutions, compounding the following groups: G1--95% ethanol, G2--70% ethanol, G3
      -70% isopropyl alcohol, or G4--eucalyptol. The dentin was scrubbed until the
      cement residues could not be visually detected. Sections were then processed for
      SEM and evaluated at * 500 magnification. Scores were attributed to each image
      according to the area covered by residual sealer, and data were subjected to
      Kruskal-Wallis at 5% significance. Eucalyptol promoted the most adequate dentin
      cleaning, although no statistical difference was detected amongst the groups (P >
      0.05), except between the eucalyptol and 70% ethanol groups (P < 0.05). All the
      evaluated dentin cleaning solutions were unable to completely remove the cement
      residues from the dentin surface.

PMID- 22419603
TI  - Early statin treatment prior to primary PCI for acute myocardial infarction:
      REPERATOR, a randomized placebo-controlled pilot trial.
AB  - OBJECTIVE: The aim of this pilot study was to determine whether early
      atorvastatin treatment will reduce left ventricle (LV) remodeling, infarct size,
      and improve microvascular perfusion. BACKGROUND: In animal studies, early statin
      therapy reduces reperfusion injury after a percutaneous coronary intervention
      (PCI) for acute myocardial infarction (AMI). METHODS: Forty-two consecutive
      patients (82% male, mean age 61.2 +/- 9.8) who underwent a primary PCI for a
      first ST-elevated AMI were randomized for pretreatment with atorvastatin 80 mg (n
      = 20) or placebo (n = 22) and continued with the same dosage daily for 1 week.
      All patients received atorvastatin 80 mg once daily 7 days after primary PCI. The
      LV function and infarct size were measured by magnetic resonance imaging within 1
      day, at 1 week, and 3 months follow up. The primary endpoint was the end-systolic
      volume index (ESVI) at 3 months. Secondary endpoints were global LV function
      measurements, myocardial infarct size, biochemical cardiac markers, TIMI flow,
      and ST-T elevation resolution. RESULTS: ESVI 3 months after AMI was 25.1 mL/m(2)
      in the atorvastatin arm and 25.0 mL/m(2) in the placebo arm (P = 0.74). The
      differences in change from baseline to 3 months follow up in global LV function
      and myocardial infarct size did not differ between both treatment arms.
      Furthermore, biochemical markers, TIMI flow, and ST-T elevation resolution did
      not differ between atorvastatin and placebo arm. CONCLUSIONS: In this pilot
      study, pretreatment with atorvastatin in an acute myocardial infarction does not
      result in an improved cardiac function, microvascular perfusion, or decreased
      myocardial infarct size.

PMID- 22419604
TI  - Modeling between-subject and within-subject variances in ecological momentary
      assessment data using mixed-effects location scale models.
AB  - Ecological momentary assessment and/or experience sampling methods are
      increasingly used in health studies to study subjective experiences within
      changing environmental contexts. In these studies, up to 30 or 40 observations
      are often obtained for each subject. Because there are so many measurements per
      subject, one can characterize a subject's mean and variance and can specify
      models for both. In this article, we focus on an adolescent smoking study using
      ecological momentary assessment where interest is on characterizing changes in
      mood variation. We describe how covariates can influence the mood variances and
      also extend the statistical model by adding a subject-level random effect to the
      within-subject variance specification. This permits subjects to have influence on
      the mean, or location, and variability, or (square of the) scale, of their mood
      responses. These mixed-effects location scale models have useful applications in
      many research areas where interest centers on the joint modeling of the mean and
      variance structure.

PMID- 22419605
TI  - Synthesis, biological activity, and ADME properties of novel S-DABOs/N-DABOs as
      HIV reverse transcriptase inhibitors.
AB  - Previous studies aimed at exploring the SAR of C2-functionalized S-DABOs
      demonstrated that the substituent at this position plays a key role in the
      inhibition of both wild-type RT and drug-resistant enzymes, particularly the
      K103N mutant form. The introduction of a cyclopropyl group led us to the
      discovery of a potent inhibitor with picomolar activity against wild-type RT and
      nanomolar activity against many key mutant forms such as K103N. Despite its
      excellent antiviral profile, this compound suffers from a suboptimal ADME profile
      typical of many S-DABO analogues, but it could, however, represent a promising
      candidate as an anti-HIV microbicide. In the present work, a new series of S
      DABO/N-DABO derivatives were synthesized to obtain additional SAR information on
      the C2-position and in particular to improve ADME properties while maintaining a
      good activity profile against HIV-1 RT. In vitro ADME properties (PAMPA
      permeation, water solubility, and metabolic stability) were also experimentally
      evaluated for the most interesting compounds to obtain a reliable indication of
      their plasma levels after oral administration.

PMID- 22419607
TI  - Conversations in cardiology: using new media to transmit timely medical
      knowledge. How do you assess the left main stenosis with FFR and IVUS in a
      patient with multivessel CAD?
AB  - Conversations in Cardiology is a new use of modern email communication to
      facilitate transfer of medical knowledge. In this Conversation in Cardiology, Dr.
      Barry Uretsky of Little Rock Arkansas asked a question about a patient with left
      main narrowing and the assessment by FFR and IVUS and several well known expert
      interventionalists address the clinical dilemma. Their answers and rebuttals are
      reflective of areas of agreement and disagreement and demonstrate the educational
      value of this format from expert opinion on problems not readily addressed by
      reference books or formal data studies.

PMID- 22419606
TI  - Metabolism of [U-13 C]glucose in human brain tumors in vivo.
AB  - Glioblastomas and brain metastases demonstrate avid uptake of 2-[(18) F]fluoro-2
      deoxyglucose by positron emission tomography and display perturbations of
      intracellular metabolite pools by (1) H MRS. These observations suggest that
      metabolic reprogramming contributes to brain tumor growth in vivo. The Warburg
      effect, excess metabolism of glucose to lactate in the presence of oxygen, is a
      hallmark of cancer cells in culture. 2-[(18) F]Fluoro-2-deoxyglucose-positive
      tumors are assumed to metabolize glucose in a similar manner, with high rates of
      lactate formation relative to mitochondrial glucose oxidation, but few studies
      have specifically examined the metabolic fates of glucose in vivo. In particular,
      the capacity of human brain cancers to oxidize glucose in the tricarboxylic acid
      cycle is unknown. Here, we studied the metabolism of human brain tumors in situ.
      [U-(13) C]Glucose (uniformly labeled glucose, i.e. d-glucose labeled with (13) C
      in all six carbons) was infused during surgical resection, and tumor samples were
      subsequently subjected to (13) C NMR spectroscopy. The analysis of tumor
      metabolites revealed lactate production, as expected. We also determined that
      pyruvate dehydrogenase, turnover of the tricarboxylic acid cycle, anaplerosis and
      de novo glutamine and glycine synthesis contributed significantly to the ultimate
      disposition of glucose carbon. Surprisingly, less than 50% of the acetyl-coenzyme
      A pool was derived from blood-borne glucose, suggesting that additional
      substrates contribute to tumor bioenergetics. This study illustrates a convenient
      approach that capitalizes on the high information content of (13) C NMR
      spectroscopy and enables the analysis of intermediary metabolism in diverse
      cancers growing in their native microenvironment.

PMID- 22419608
TI  - Noonan-like syndrome with loose anagen hair associated with growth hormone
      insensitivity and atypical neurological manifestations.
AB  - Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM 607721), recently
      related to the invariant c.4A>G missense change in SHOC2, is characterized by
      features reminiscent of Noonan syndrome. Ectodermal involvement, short stature
      associated with growth hormone (GH) deficiency (GHD), and cognitive deficits are
      common features. We report on a patient with molecularly confirmed NS/LAH
      exhibiting severe short stature associated with GH insensitivity (GHI), and
      chronic complex tics, a neurological feature never described before in this
      syndrome. IGF1 generation test revealed only a blunted increase in IGF1 after
      exogenous GH treatment, revealing mild GH insensitivity associated with proper
      STAT5 activation. Most common causes of secondary tics in childhood were
      excluded.

PMID- 22419609
TI  - Adenovirus-mediated hepatocarcinoma-intestine-pancreas/pancreatitis-associated
      protein suppresses dextran sulfate sodium-induced acute ulcerative colitis in
      rats.
AB  - BACKGROUND: Although increased expression of hepatocarcinoma-intestine
      pancreas/pancreatitis-associated protein (HIP/PAP) has been reported in
      ulcerative colitis (UC), its role in UC remains unclear. This study was designed
      to assess the function of HIP/PAP in experimental UC and further to explore its
      underlying mechanisms. METHODS: Recombinant adenovirus was prepared to mediate
      ectopic expression of HIP/PAP in the colon of rats. The effect of HIP/PAP on
      dextran sodium sulfate (DSS)-induced colitis was assessed by disease activity
      index (DAI), macroscopic, and histological evaluations. Superoxide dismutase
      (SOD) and myeloperoxidase (MPO) activities, malondialdehyde (MDA) content, and
      tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) production were
      determined in colonic mucosa. Proliferation cell nuclear antigen (PCNA) was
      immunostained to reflect the proliferation of colonic epithelia. The effects of
      HIP/PAP on proliferation and H(2)O(2) -induced apoptosis of SW480 and LoVo
      colonic adenocarcinoma cells were also determined. Gene expression profiles in
      SW480 after HIP/PAP overexpression were analyzed by microarray analysis. RESULTS:
      The protective effect of HIP/PAP against DSS-induced colitis in rats was
      confirmed. Ectopic expression of HIP/PAP resulted in attenuation of oxidative
      damage, reduction of TNF-alpha and IL-6 expression, and elevation of epithelial
      proliferation in colonic mucosa and led to decreased apoptosis and increased
      proliferation in colonic adenocarcinoma cells. Microarray analysis revealed
      altered expression of inflammation-related molecules, growth factors,
      proliferation-related molecules, and antioxidant enzymes under overexpression of
      HIP/PAP. CONCLUSIONS: HIP/PAP has a protective effect against DSS-induced colitis
      in rats via inhibiting inflammation, alleviating oxidative damage, and promoting
      colonic epithelium regeneration. HIP/PAP might represent a new promising
      therapeutic strategy in UC.

PMID- 22419610
TI  - Virus present in the reproductive tract of asymptomatic drones of honey bee (Apis
      mellifera l.), and possible infection of queen during mating.
AB  - Virus particles and viral inclusions were detected by transmission electron
      microscopy examination of sections of the seminal vesicles and mucus gland of
      asymptomatic young drones from colonies of Apis mellifera lightly infested by
      Varroa mite. In the mucus gland the infection was found in the muscular sheath
      and epithelium, while in the seminal vesicle in cells of the outer serosa.
      Isolated viral particles were also observed in the hemolymph occupying the
      intercellular spaces of the muscular sheath fibers. In the muscle the virus
      appeared as polygonal crystalloid inclusions, while in the epithelium mainly
      inside cytoplasmic vesicles. The infected cells apparently are not damaged. The
      virus particles are present in the hemolymph and forming more mature structures,
      as crystalloids, in the muscle. This suggests that the virus is liberated in the
      body fluid and infects the tissues penetrating the cells through endocytosis. The
      presence of virus in mucus gland epithelial vesicles raise the possibility of its
      transference to the gland secretion and therefore, to the semen.

PMID- 22419611
TI  - Procedural and clinical outcomes of the valve-in-valve technique for severe
      aortic insufficiency after balloon-expandable transcatheter aortic valve
      replacement.
AB  - OBJECTIVE: To describe the clinical and procedural outcomes of patients treated
      with the valve-in-valve technique for severe aortic insufficiency (AI) after
      balloon-expandable transcatheter aortic valve replacement (TAVR). BACKGROUND:
      Severe AI immediately after valve implantation is a notable complication of TAVR.
      It can be treated with a valve-in-valve technique which involves deploying a
      second valve within the first one to crush the leaflets of the first implant
      leaving a new functional valve. METHODS: We analyzed data on 142 consecutive
      patients at our institution undergoing TAVR with the Sapien valve between
      November of 2007 and April of 2011. Etiologies of acute AI, procedural and
      intermediate term clinical outcomes were reported for those in whom a valve-in
      valve procedure was necessary. Post-hoc analysis of these cases with C-THV
      imaging (Paieon Medical Ltd.) was performed to elucidate the mechanism for
      successful AI treatment. RESULTS: A total of 5 of 142 (3.5%) patients were
      treated with the valve-in-valve technique. Etiologies of the aortic valve
      insufficiency included bioprosthesis malposition (n = 3), valve dysfunction (n =
      1), and valve undersizing (n = 1). With placement of the second valve, the first
      valve dimensions increased to approach the nominal valve size while the second
      valve size remained less than nominal. CONCLUSIONS: The valve-in-valve technique
      is an appropriate bailout measure for patients with acute valvular AI after
      balloon-expandable TAVR.

PMID- 22419612
TI  - Analysis of multiple exposures in the case-crossover design via sparse
      conditional likelihood.
AB  - We adapt the least absolute shrinkage and selection operator (lasso) and other
      sparse methods (elastic net and bootstrapped versions of lasso) to the
      conditional logistic regression model and provide a full R implementation. These
      variable selection procedures are applied in the context of case-crossover
      studies. We study the performances of conventional and sparse modelling
      strategies by simulations, then empirically compare results of these methods on
      the analysis of the association between exposure to medicinal drugs and the risk
      of causing an injurious road traffic crash in elderly drivers. Controlling the
      false discovery rate of lasso-type methods is still problematic, but this problem
      is also present in conventional methods. The sparse methods have the ability to
      provide a global analysis of dependencies, and we conclude that some of the
      variants compared here are valuable tools in the context of case-crossover
      studies with a large number of variables.

PMID- 22419613
TI  - The extension peptide of plant ferritin from sea lettuce contributes to shell
      stability and surface hydrophobicity.
AB  - Plant ferritins have some unique structural and functional features. Most of
      these features can be related to the plant-specific "extension peptide" (EP),
      which exists in the N-terminus of the mature region of a plant ferritin. Recent
      crystallographic analysis of a plant ferritin revealed the structure of the EP,
      however, two points remain unclear: (i) whether the structures of well-conserved
      EP of plant ferritins are common in all plants, and (ii) whether the EP truly
      contributes to the shell stability of the plant ferritin oligomer. To clarify
      these matters, we have cloned a green-plant-type ferritin cDNA from a green alga,
      Ulva pertusa, and investigated its crystal structure. Ulva pertusa ferritin
      (UpFER) has a plant-ferritin-specific extension peptide composed of 28 amino acid
      residues. In the crystal structure of UpFER, the EP lay on and interacted with
      the neighboring threefold symmetry-related subunit. The amino acid residues
      involved in the interaction were very highly conserved among plant ferritins. The
      EPs masked the hydrophobic pockets on the ferritin shell surface by lying on
      them, and this made the ferritin oligomer more hydrophilic. Furthermore,
      differential scanning calorimetric analysis of the native and its EP-deletion
      mutant suggested that the EP contributed to the thermal stability of the plant
      ferritin shell. Thus, the shell stability and surface hydrophobicity of plant
      ferritin were controlled by the presence or absence of the plant-ferritin
      specific EP. This regulation can account for those processes such as shell
      stability, degradation, and association of plant ferritin, which are
      significantly related to iron utilization in plants.

PMID- 22419614
TI  - Improved regeneration of autologous transplanted lymph node fragments by VEGF-C
      treatment.
AB  - Secondary lymphedema is a common complication after removal of lymph nodes in
      combination with radiation therapy in the treatment of breast cancer, cervical
      cancer, and melanomas. Only symptomatic therapies are available at the moment,
      and lymphedema is for most patients a lifelong condition involving psychological
      and physical disabilities. Animal models exist to study the pathophysiology of
      lymphedema but not to study surgical treatments. The aim of this study was to
      show that regeneration of autologous transplanted lymph node fragments is
      possible in rats that were irradiated previously locally in the groin and to
      examine the effects of vascular endothelial growth factor (VEGF)-C injections on
      the rate of regeneration of transplanted lymph nodes. In all of the animals,
      inguinal and popliteal lymph nodes and adjacent lymphatic vessels were
      unilaterally removed and the inguinal region irradiated by a single dose of 15
      Gy. Afterward, lymph node fragments were transplanted subcutaneously in the
      irradiated region. Half of the animals were treated by local VEGF-C injections
      after transplantation. Four weeks after transplantation, drainage of the leg was
      tested by injection of blue dye, and the transplanted fragments were removed and
      examined immunohistologically. We could show that regeneration of autologous
      transplanted lymph node fragments is possible in areas treated with radiotherapy
      in the rat. We also documented that transplants can achieve a connection to the
      lymphatic collectors of the leg. The results suggest that the outcome of
      regeneration can be improved by injection of VEGF-C in the transplantation area.
      Thus, lymph node fragment regeneration may be relevant for lymphedema prevention
      and therapy.

PMID- 22419615
TI  - Risk factors for nonsyndromic holoprosencephaly: a Manitoba case-control study.
AB  - Holoprosencephaly (HPE) is one of the most common developmental field defects,
      occurring in 1 in 250 conceptuses and in 1 in 10,000-20,000 live births. Nearly
      half of patients with HPE have a recognized syndrome or a single gene defect.
      However, little is known about the risk factors for the remainder with
      "nonsyndromic" HPE. In our case-control study, we examine factors associated with
      nonsyndromic HPE. We identified 47 patients with HPE from the genetics clinic
      database with an equal number of controls matched for gender and birthdate. Of
      the 47 patients, 23 were identified as nonsyndromic. No statistically significant
      differences were noted between the mean maternal and paternal ages of patients
      and controls. Factors associated with nonsyndromic HPE were: having an Aboriginal
      mother (unadjusted odds ratio [OR] 3.5, 95% confidence interval [CI] 1.1-11.1),
      an Aboriginal father (OR 12.8, 95% CI 3.0-55.1), at least one Aboriginal parent
      (OR 5.0, 95% CI 1.6-16.0), or two Aboriginal parents (OR 8.8, 95% CI 2.0-37.8),
      the presence of a family history of a midline facial defect (OR 8.2, 95% CI 1.5
      45.2), and being of low socioeconomic status (OR 3.0, 95% CI 1.0-9.1). Having an
      Aboriginal background remained statistically significant after adjusting for low
      socioeconomic status. Other associations evaluated--history of prior spontaneous
      abortion, stillbirth, neonatal death, prepregnancy diabetes, infections during
      pregnancy, alcohol exposure, smoking, and substance abuse--were not significantly
      associated with nonsyndromic HPE. The use of periconceptional folic acid or
      vitamins was not associated with a lower risk of nonsyndromic HPE.

PMID- 22419616
TI  - Transcatheter embolization of anomalous systemic arterial supply with Amplatzer
      Vascular Plugs II in Scimitar syndrome.
AB  - A 57-year-old woman suffering from recurrent pneumonia and considered to be high
      risk for surgical correction of an atrial septal defect (ASD) associated with a
      right lung sequestration vascularized by arteries coming from the abdominal aorta
      and an abnormal venous drainage into the inferior vena cava (Scimitar syndrome).
      Therefore stepwise transcatheter approach was offered as an alternative
      treatment. We performed ASD closure and embolization of the anomalous systemic
      arterial supply using Amplatzer Vascular Plugs II. The abnormal venous drainage
      was conservatively treated (Q(p) /Q(s) : 1.1/1 after ASD closure and anomalous
      arterial supply embolization). At 24-month follow-up, no recurrent pneumonia was
      reported, functional class improved and right cardiac cavities normalized.

PMID- 22419617
TI  - High mucosal healing rates in 5-ASA-treated ulcerative colitis patients: results
      of a meta-analysis of clinical trials.
AB  - BACKGROUND: Recently, mucosal healing (MH) is regarded as an important treatment
      goal in ulcerative colitis (UC). 5-Aminosalicylates (5-ASA) are the standard
      treatment in mild-to-moderate UC, but the effect on MH is less known. The aim of
      this study was to systematically review the medical literature in order to
      compare different preparations of 5-ASA for the effect on MH. METHODS: We
      conducted a structured search of PubMed and the Cochrane Central Register of
      Controlled Trials to identify randomized controlled clinical trials with 5-ASA in
      UC providing data about MH. We calculated the sample size-weighted pooled
      proportion of patients with MH, and performed meta-analysis of head-to-head
      comparisons. RESULTS: Out of 645 hits, we included 90 treatment arms, involving
      3977 patients using oral 5-ASA (granulate and tablets) and 2513 patients using
      rectal 5-ASA (suppositories, enema, and foam). Overall, 43,7% of 5-ASA treated
      patients achieved MH (oral 36,9%; rectal 50,3%). In oral studies, 49% of patients
      using granulate (7 treatment-arms) achieved MH compared to 34,9% using tablets
      (43 treatment-arms). In rectal studies the proportion of MH was 62% for
      suppositories (eight treatment arms), 51% for foam (nine treatment arms), and 46%
      for enema (23 treatment arms), respectively. CONCLUSIONS: 5-ASA preparations
      achieved MH in nearly 50% of UC patients. There were no significant differences
      in MH between the various 5-ASA agents, either in the oral or the rectal
      treatment groups.

PMID- 22419618
TI  - Morphological gradient based adapted selective filter for removal of Rician noise
      from magnetic resonance images.
AB  - Feature/edge-preserving noise removal techniques have a strong potential in
      several application domains including medical image processing. Magnetic
      resonance (MR) images have a tendency to gain Rician noise during acquisition. In
      this article, we have presented genetic algorithms based adapted selective non
      local means (GASNLM) filter-based scheme for noise suppression of MR images while
      preserving the image features as much as possible. We have applied GASNLM filter
      with optimal parameter values for different frequency image regions to remove the
      noise. Filter parameter values are optimized by genetic algorithm (GA). A change
      in NLM filter known as selective weight matrix is also proposed to preserve the
      image features. The results prove soundness of the method. We have compared
      results with many well known and latest techniques, and the improvements are
      discussed.

PMID- 22419619
TI  - Upper cavo-pulmonary anastomosis by transcatheter technique.
AB  - OBJECTIVES: The aim of this animal study was to establish a shunt connection
      between superior vena cava (SVC) and right pulmonary artery (RPA) by
      transvascular intervention solely. BACKGROUND: After initial shunt creation, the
      establishment of the upper cavo-pulmonary anastomosis (UCPA) is the second out of
      three open chest operations young infants with univentricular anatomy are
      subjected to. To avoid the risks of reoperation with cardiovascular bypass, we
      sought to replace this surgical step by an interventional technique. METHODS:
      After cannulation of jugular and femoral veins in four piglets (mean body weight
      of 12.5 kg) an UCPA was created by radiofrequency perforation from the SVC across
      the right atrium into the RPA and subsequent implantation of covered stents. The
      perforation was guided by biplane fluoroscopy and the perforation wire premounted
      with a coaxial catheter was advanced into the distal pulmonary artery and
      exchanged for a stiffer wire. A long sheath was brought into the RPA and an 80 mm
      long expanded poly-tetra-fluoro-ethylene (ePTFE)-covered Cheatham Platinum stent
      was then implanted connecting the SVC with the RPA. RESULTS: Immediate
      angiography showed antegrade flow from SVC to RPA. Angiographic re-evaluation
      after a median period of 4 weeks showed partial in-stent stenosis but patent
      lumina. Additionally, veno-venous collaterals from the SVC to the right atrium
      had developed. Histology of the explanted stents revealed parietal thrombi and
      mild to moderate pseudo intima proliferation inside the lumina. CONCLUSIONS: The
      transvascular creation of an upper unidirectional cavo-pulmonary anastomosis in
      piglets is technically feasible using standard catheterization equipment.

PMID- 22419620
TI  - Photovoice: an opportunity and challenge for students' genuine participation.
AB  - It has been highlighted that youth empowerment and participation are important
      principles for school health promotion. Despite this fact, children and youth are
      rarely given instruments to participate or to influence their situations and the
      environments in their schools. Photovoice is a method to increased empowerment
      and participation. Originally it was created as a community action research
      method based on Freire's critical pedagogy and feminist theory. The purpose of
      this study was to explore challenges and opportunities for applying photovoice in
      a school setting to support genuine participation. Together with teachers and
      students in an upper secondary school in Ostersund's municipality in the north of
      Sweden, the photovoice method was field tested and modified to a classroom
      situation. The teachers and the students were interviewed about their experiences
      with the method. The results were interpreted by content analysis and showed that
      the teachers' capability to be facilitators and the students' possibility to make
      a difference for the school or the municipality were the most important factors
      to succeed with photovoice. The conclusions were that photovoice challenges
      schools and society to have a better structure for genuine participation if youth
      participation is seen as valuable. 

PMID- 22419621
TI  - Tackling 'wicked' health promotion problems: a New Zealand case study.
AB  - This paper reports on a complex environmental approach to addressing 'wicked'
      health promotion problems devised to inform policy for enhancing food security
      and physical activity among Maori, Pacific and low-income people in New Zealand.
      This multi-phase research utilized literature reviews, focus groups, stakeholder
      workshops and key informant interviews. Participants included members of affected
      communities, policy-makers and academics. Results suggest that food security and
      physical activity 'emerge' from complex systems. Key areas for intervention
      include availability of money within households; the cost of food; improvements
      in urban design and culturally specific physical activity programmes. Seventeen
      prioritized intervention areas were explored in-depth and recommendations for
      action identified. These include healthy food subsidies, increasing the statutory
      minimum wage rate and enhancing open space and connectivity in communities. This
      approach has moved away from seeking individual solutions to complex social
      problems. In doing so, it has enabled the mapping of the relevant systems and the
      identification of a range of interventions while taking account of the views of
      affected communities and the concerns of policy-makers. The complex environmental
      approach used in this research provides a method to identify how to intervene in
      complex systems that may be relevant to other 'wicked' health promotion problems.

PMID- 22419622
TI  - Recall, relevance and application of an in-school sexual and reproductive health
      intervention 7-9 years later: perspectives of rural Tanzanian young people.
AB  - Many adolescent sexual and reproductive health (ASRH) interventions have improved
      knowledge and reduced reported sexual risk behaviours, but found no impact on
      HIV. We explored potential reasons for this in 23 in-depth interviews, conducted
      7-9 years after exposure to ASRH intervention. We discussed participants'
      memories and views of the relevance of the in-school intervention, and their
      subsequent ability to apply what they had learned. While most participants had
      favourable memories of the intervention, few recalled specific details. Most
      reported that the intervention had been relevant, although few reported being
      able to apply the teachings. Men found it easier to apply lessons about condoms
      than women. Inability to apply the intervention teachings was often linked to
      cultural norms around fertility and/or gender power relations. ASRH interventions
      should address structural factors such as the quality of parenting and explicitly
      link interventions to young peoples' future aspiration. 

PMID- 22419623
TI  - Status of national guidelines in dictating individual clinical practice and
      defining negligence.

PMID- 22419624
TI  - Potential use of melatonin in sleep and delirium in the critically ill.
AB  - Intensive care delirium is a well-recognized complication in critically ill
      patients. Delirium is an independent risk factor for death in the intensive care
      unit (ICU), leading to oversedation, increased duration of mechanical
      ventilation, and increased length of stay. Although there has not been a direct
      causal relationship shown between sleep deprivation and delirium, many studies
      have demonstrated that critically ill patients have an altered sleep pattern,
      abnormal levels of melatonin, and loss of circadian rhythms. Melatonin has a
      major role in control of circadian rhythm and sleep regulation and other effects
      on the immune system, neuroprotection, and oxidant/anti-oxidant activity. There
      has been interest in the use of exogenous melatonin as a measure to improve
      sleep. However, there are only a few studies of melatonin in ICU patients and
      these use heterogeneous methodologies. Therefore, it is not possible at this
      stage to make any clear recommendations regarding the clinical use of melatonin
      in this setting. There is a need for well-designed randomized controlled trials
      examining the role of melatonin in ICU.

PMID- 22419625
TI  - Force and pressure distribution using Macintosh and GlideScope laryngoscopes.

PMID- 22419627
TI  - Anti-platelet therapy in non-cardiac elective surgery.

PMID- 22419629
TI  - Maternal temperature increase.

PMID- 22419631
TI  - Convulsions after normal dose of lidocaine: a probable drug interaction.

PMID- 22419632
TI  - Fulminant rhabdomyolysis after prolonged radical prostatectomy managed with
      continuous veno-venous haemodialysis, regional citrate anticoagulation, and a
      polysulphone high-flux filter.

PMID- 22419633
TI  - Efficacy of rocuronium and sugammadex in a patient with dermatomyositis.

PMID- 22419634
TI  - Ultrasound and regional blocks.

PMID- 22419635
TI  - Delayed subdural haematoma complicated by abducens nerve palsy and cortical vein
      thrombosis after obstetric epidural anaesthesia.

PMID- 22419640
TI  - Contraceptive use and barriers to access among newly arrested women.
AB  - Incarcerated women report high rates of prior unintended pregnancies as well as
      low contraceptive use. Because jail could be a site of contraception care, this
      study aimed to assess women's access to contraception prior to their arrest. A
      cross-sectional survey was administered to 228 reproductive-aged, nonpregnant
      women arrested in San Francisco. Twenty-one percent were currently using
      contraception. More than half (61%) had not used contraception in the last year,
      yet 11% wanted to have used it. Women in this latter subset reported greater
      difficulty with payment, finding a clinic, and transportation compared to women
      who had used contraception. In addition, 60% of all women in the sample would
      accept contraception if offered to them in jail. Thus, jail is a potentially
      important and acceptable point of access to contraception, which can circumvent
      some preincarceration logistical barriers.

PMID- 22419642
TI  - Chlamydia and gonorrhea screening using urine-based nucleic acid amplification
      testing among males entering New York City jails: a pilot study.
AB  - This article describes a pilot screening program to detect Chlamydia trachomatis
      (Ct) and Neisseria gonorrhoeae (Ng) sexually transmitted infections (STIs) in
      adolescent and adult males newly incarcerated in New York City jails using urine
      based nucleic acid amplification technology (NAAT). Between December 8 and 22,
      2003, 2,417 males were tested; 162 (6.7%) were found positive for Ct and/or Ng
      STIs, with 138 (86.8%) exhibiting no STI signs or symptoms and 102 (63%) treated
      prior to jail release. Younger age, positive urine leukocyte esterase test, and
      >=11 recent sex partners were predictors of STI. Urine-based screening and
      treatment was feasible in this setting and identified STI that would otherwise
      have been undetected. Jails may thus be important venues for targeted male STI
      screening.

PMID- 22419641
TI  - Isoniazid vs. rifampin for latent tuberculosis infection in jail inmates:
      toxicity and adherence.
AB  - This open-label randomized trial compared isoniazid (9 months) to rifampin (4
      months) on toxicity and completion in a jailed population with latent
      tuberculosis infection. Rifampin resulted in fewer elevated liver function tests
      (risk ratio [RR] 0.39, 95% confidence interval [CI] [0.18, 0.86]) and less
      toxicity requiring medication withdrawal (RR 0.51, 95% CI [0.13, 2.01]), although
      one participant receiving rifampin experienced an allergic reaction. Completion
      was achieved for 33% receiving rifampin compared to 26% receiving isoniazid (p =
      .10). With careful monitoring rifampin is a safe and less toxic regimen and
      appears to be a reasonable alternative because of its shorter duration, allowing
      more people to complete treatment behind bars. Therapy completion in released
      inmates is unacceptably low and ensuring follow-up after discharge must be part
      of a decision to treat.

PMID- 22419643
TI  - Substance use and sexual behavior among men prior to parole revocation:
      prevalence and correlates.
AB  - Men's risk behavior during a 3-month period prior to parole revocation was
      assessed. Frequent alcohol use was higher among men who had more children, were
      homeless, or had a history of alcohol and other drug abuse treatment. The use of
      drugs was greater among men who were younger or had a history of sexually
      transmitted infection (STI). The use of hard drugs was higher among men who had
      history of injection drug use. Unprotected vaginal or anal sex was increased
      among men who were younger, single, or had a history of STIs. Sex with a high
      risk partner was greater among men who were older, used hard drugs, or had a
      history of STIs. Findings highlight the importance of developing risk-reduction
      programs for men on parole.

PMID- 22419644
TI  - Prevalence of psychiatric disorders in the Texas juvenile correctional system.
AB  - Most studies assessing the burden of psychiatric disorders in juvenile
      correctional facilities have been based on small or male-only samples or have
      focused on a single disorder. Using electronic data routinely collected by the
      Texas juvenile correctional system and its contracted medical provider
      organization, we estimated the prevalence of selected psychiatric disorders among
      youths committed to Texas juvenile correctional facilities between January 1,
      2004, and December 31, 2008 (N = 11,603). Ninety-eight percent were diagnosed
      with at least one of the disorders. Highest estimated prevalence was for conduct
      disorder (83.2%), followed by any substance use disorder (75.6%), any bipolar
      disorder (19.4%), attention-deficit/hyperactivity disorder (18.3%), and any
      depressive disorder (12.6%). The estimated prevalence of psychiatric disorders
      among these youths was exceptionally high and showed patterns by sex,
      race/ethnicity, and age that were both consistent and inconsistent with other
      juvenile justice samples.

PMID- 22419645
TI  - Differentiated adipose-derived stem cells promote myelination and enhance
      functional recovery in a rat model of chronic denervation.
AB  - Transplantation of autologous Schwann cells (SCs) is a promising approach for
      treating various peripheral nerve disorders, including chronic denervation.
      However, given their drawbacks, such as invasive biopsy and lengthy culture in
      vitro, alternative cell sources would be needed. Adipose-derived stem cells
      (ASCs) are a candidate, and in this study rat ASCs transdifferentiated into a SC
      phenotype (dASC) cocultured with dorsal root ganglion neurons were shown to
      associate with neurites and to express myelin basic protein (MBP)-positive myelin
      protein. Furthermore, dASCs transplanted into a chronically denervated rat common
      peroneal nerve survived for at least for 10 weeks, maintaining their
      differentiated state. Immunohistochemical analysis revealed that transplanted
      dASCs associated with regenerating axons, forming MBP-/protein zero-positive
      myelin sheaths. The cell survival and myelin expression assessed by double
      labelling with S100 and glial fibrillary acidic protein were similar between the
      dASC- and SC-transplanted nerves. Importantly, transplantation of dASCs resulted
      in dramatically improved motor functional recovery and nerve regeneration, with a
      level comparable to, or even superior to, transplantation of SCs. In conclusion,
      dASCs are capable of myelinating axons in vivo and enhancing functional outcome
      after chronic denervation.

PMID- 22419646
TI  - Synchrotron X-ray microscopic computed tomography of the pump system of a female
      mosquito.
AB  - The pumping organ of blood-sucking female mosquitoes has a three-dimensional (3D)
      structure. However, conventional two-dimensional imaging methods are insufficient
      for visualizing the 3D structure in detail. Furthermore, their 3D imaging tasks
      are highly time consuming and sample preparation process requires elaborate
      skill. Among 3D imaging techniques, synchrotron X-ray microscopic computed
      tomography (SR-MUCT) is especially suitable for small insects with opaque
      cuticles, such as mosquitoes. In this study, the 3D morphological structure of
      the pump system of a female mosquito was visualized using SR-MUCT. Expandable
      volume capacities of two pump chambers were measured for several mosquito samples
      of similar size. To verify the cross-sectional images acquired by SR-MUCT,
      complementary paraffin-sectioning data were compared.

PMID- 22419647
TI  - Influence of mesterolone on satellite cell distribution and fiber morphology
      within maturing chicken pectoralis muscle.
AB  - Mesterolone is a synthetic oral anabolic androgenic steroid used to treat
      hypogonadism. There are frequent reports of mesterolone abuse in human and equine
      sports to increase muscle mass and strength. However, limited information is
      available about how this drug exerts its effects on skeletal muscle. Satellite
      cells (SCs) are mononuclear myogenic stem cells that contribute to postnatal
      muscle growth and repair. As SC activation and subsequent differentiation to new
      myonuclei is a major event during muscle hypertrophy, this study investigated the
      influence of mesterolone on SC distribution within the pectoralis muscle of
      chickens. Specifically, this study tested the hypotheses that mesterolone induces
      avian skeletal muscle hypertrophy, and that mesterolone increases the number of
      SCs in avian skeletal muscle. Robust immunocytochemical techniques and
      morphometric analyses were used to calculate the numbers of SCs and myonuclei.
      Also, DNA concentration and Pax7 protein levels were measured to confirm
      immunocytochemical findings. Mesterolone significantly increased pectoralis mass
      and fiber size. All SC indices and number of myonuclei increased significantly by
      mesterolone administration. In addition, greater DNA concentration and Pax7
      protein expression were found in mesterolone-treated birds. This study indicates
      that mesterolone can induce avian skeletal muscle hypertrophy and that this is
      correlated with increased number of SCs. We suggest that SCs are key cellular
      intermediaries for mesterolone-induced muscle hypertrophy.

PMID- 22419648
TI  - Percutaneous closure of an atrial septal defect in an infant with Shone's
      syndrome.
AB  - Rarely is closure of the atrial septal defect indicated in infants. Yet, an
      atrial septal defect in the presence of congenital mitral stenosis may cause
      significant congestive heart failure in infancy. We present the case of an infant
      with Shone's syndrome, left ventricular hypoplasia, and a large ostium secundum
      atrial septal defect who developed pulmonary overcirculation following repair of
      coarctation of the aorta. The infant underwent cardiac catheterization,
      hemodynamic assessment, and successful percutaneous closure of the atrial septal
      defect. The patient improved dramatically following the intervention. Follow-up
      echocardiograms have demonstrated growth of mitral valve annulus diameter and
      left ventricular dimensions. Atrial septal defect closure in this small infant
      was associated with immediate improved clinical status, and improved growth of
      the left heart structures.

PMID- 22419650
TI  - Calcifying leukoencephalopathies: new overlapping phenotypes.

PMID- 22419649
TI  - Exclusive antagonism of the alpha4 beta7 integrin by vedolizumab confirms the gut
      selectivity of this pathway in primates.
AB  - BACKGROUND: Biological therapies that antagonize specific molecules have
      demonstrated efficacy in inflammatory bowel diseases, but infections resulting
      from systemic immunosuppression underscore the need for safer therapies. The
      objective of this investigation was to determine if antagonism of the alpha(4)
      beta(7) integrin would exclusively yield gut-selective antiinflammatory activity
      in primates. METHODS: A series of experiments were conducted to investigate
      potential intra- and extraintestinal effects in healthy nonhuman primates dosed
      repeatedly with the alpha(4) beta(7) -exclusive antagonist vedolizumab (former
      versions: MLN0002, MLN02, LDP-02) for 4, 13, and 26 weeks. RESULTS: No adverse
      clinical effects of vedolizumab were observed in healthy cynomolgus monkeys up to
      the highest doses tested (100 mg/kg). Histomorphologic analyses indicated a
      reduction in the frequency of leukocytes in gastrointestinal tissue, but not
      other organs. A significant (P < 0.05) decrease in the frequency of beta 7+
      lymphocytes in gastrointestinal tissues corresponded to a significant (P < 0.05)
      increase in alpha(4) beta 7+ memory helper T lymphocytes in peripheral blood.
      This elevation was specific to alpha(4) beta 7+ memory helper T lymphocytes;
      levels of other leukocyte subsets remained unaffected. Systemic opportunistic
      infections were not observed, and vedolizumab did not inhibit adaptive or innate
      immune responses systemically. CONCLUSIONS: These data demonstrate that blocking
      the alpha(4) beta(7) integrin exclusively yields gut-selective antiinflammatory
      activity in primates.

PMID- 22419651
TI  - Impact of three-dimensional transesophageal echocardiography on prosthesis sizing
      for transcatheter aortic valve implantation.
AB  - OBJECTIVES: To compare aortic annulus diameters obtained by 3D transesophageal
      echocardiography (TEE) with 2D-TEE and the impact on prosthesis size selection in
      transcatheter aortic valve implantation (TAVI). BACKGROUND: In TAVI the aortic
      annulus diameter determines prosthesis size. The ideal modality for annulus
      assessment has not been defined yet. METHODS: Annulus diameters in 2D-TEE (long
      axis view) and in 3D-TEE (long-axis view in multiple-plane-reconstruction) were
      compared in consecutive patients with aortic stenosis screened for TAVI.
      Prosthesis size was selected according to industry guidelines, integrating data
      from 3D-TEE, angiography and computed tomography. The percentage of cases in
      which 2D-TEE and 3D-TEE correctly predicted final prosthesis size was calculated.
      RESULTS: Forty-nine patients were studied (Age 80 +/- 5, 39% male, logistic
      EuroScore 17 +/- 11%). Annulus diameters from 2D- and 3D-TEE correlated (r =
      0.808, P < 0.0001). Mean diameters were significantly larger on 3D- vs. 2D-TEE
      (23.4 +/- 2.2 vs. 22.1 +/- 2.6 mm, P < 0.001) with a mean difference of 1.2 mm
      (limits of agreement: -1.8 to 4.3). The interobserver variability of 2D- and 3D
      TEE was 3.5 +/- 5.6% and 0.9 +/- 5.1%, respectively. Thirty-nine patients
      underwent TAVI (27 CoreValveTM, 12 Edwards SapienTM). The procedure was
      successful in 37 (95%) patients. Postprocedural regurgitation was none or mild in
      89% of the cases with no severe insufficiency. Final prosthesis size was
      correctly predicted by 2D-TEE in 67% while in 80% by 3D-TEE. Overall, 3D-TEE
      suggested a different prosthesis size in 26% of all cases compared to 2D-TEE.
      CONCLUSIONS: Aortic annulus measurement by 3D-TEE yields significantly larger
      diameters than 2D-TEE. This impacts prosthesis size selection in a considerable
      percentage of cases.

PMID- 22419653
TI  - On the morphology of the worker immatures of the leafcutter ant Atta sexdens
      Linnaeus (Hymenoptera: Formicidae).
AB  - Leafcutter ants of the genus Atta Fabricius are serious agricultural pests.
      Morphological studies of immature stages within this group are few, and the data
      provided for species of considerable importance are usually incomplete. In this
      study, the immatures of Atta sexdens Linnaeus are described and compared using
      light and scanning electron microscopy. Only specimens from founding stage
      colonies (i.e., lacking adult workers) were used. The existence of four larval
      instars was estimated by a frequency plot of maximum head widths, and the larvae
      of different instars differed from each other mainly by their bodily dimensions.
      Worker larvae belonged to two distinct morphological castes: (1) gardeners and
      nurses and (2) within-nest generalists. The worker larvae described in this study
      differed from a previous description of the same species by the following traits:
      the existence of a genal lobe, the number of clypeal hairs, the presence of two
      hairs on the ninth abdominal somite, the presence of hairs on the anterior
      surface of the labrum, and the shape of the maxillary palpus. This study provides
      a comparative analysis of immature stages of A. sexdens that may be relevant to
      future morphological and biological studies of the Attini.

PMID- 22419652
TI  - Racial/ethnic differences in treatment discussed, preferred, and received for
      prostate cancer in a tri-ethnic population.
AB  - This study was conducted to explore whether racial/ethnic differences exist in
      treatment discussed, preferred, and ultimately received for localized prostate
      cancer (PCa) as epidemiological data are scant on this issue. The authors
      recruited 640 localized PCa patients from the Texas Medical Center, Houston,
      Texas, between 1996 and 2004. The authors used a structured questionnaire to
      collect data through personal interviews. Three main treatment modalities for
      localized PCa, consisting of surgery, radiation therapy, and watchful waiting,
      were considered for this study. It was found that health professionals were less
      likely to discuss surgery (odds ratio [OR] = 0.35, 95% confidence interval [CI] =
      0.18-0.68) and watchful waiting (OR = 0.53, 95% CI = 0.34-0.83) with Hispanics
      than Whites. However, African Americans were less likely to receive watchful
      waiting (OR = 0.22, 95% CI = 0.05-0.93). They were more likely to prefer (OR =
      1.23, 95% CI = 0.78-1.94) and receive (OR = 1.27, 95% CI = 0.87-1.86) radiation
      therapy, although they did not achieve statistical significance (p < .05). Higher
      age was associated with lower likelihood of discussing, preferring, and receiving
      surgical treatment. Higher Gleason sum was associated with lower likelihood of
      discussing treatment. A comparison of concordances between treatment preferred by
      patients and what was actually received, in general, showed a higher agreement
      for surgery and radiation therapy. More exploration needs to be done in other
      settings to confirm these findings.

PMID- 22419654
TI  - An experimental approach to evaluate the correspondence between wear facet
      position and occlusal movements.
AB  - The position of dental wear facets depends on crown morphology, antagonistic
      relation, and occlusal movements. The correspondence between specific directions
      of movements and the position of wear facets cannot be easily evaluated in vivo
      and has never been tested experimentally. An experimental analysis was carried
      out to provide evidence that explicit occlusal movements are responsible for the
      spatial position of wears facets. Unworn dental stone replicas of modern human
      prosthetic molar were mounted in a physical dental articulator, and the upper
      dental arch was ground against the lowers to create a wear facet pattern. The
      relief guided movements were constrained sequentially by means of three different
      condyle box setups: (1) experienced-based mean values for sagittal condyle
      inclination, lateroretrusion, Benett angle, and transversal condyle inclination
      were used; (2) pure retrusion and immediate side shift movements were added; (3)
      retrusion and immediate side shift were increased. Finally, the upper and lower
      first molars were surface scanned and macrowear facets were quantified in four
      wear stages. The results show that a wear facet pattern was created similar to
      what is seen on human molars in vivo occlusion. Some facets only developed if
      specific directions of movement were carried out. Therefore, we posit that an
      analysis of wear facet patterns is useful in recreating the individual occlusal
      movements. This information can be used not only to guide reproducible functional
      reconstructions of crown relief and dental arches but also to deduce jaw
      movements when, for example, isolated primate teeth are discovered in
      paleontological contexts.

PMID- 22419655
TI  - Energy homeostasis in Prader-Willi syndrome: how clinical research informs
      studies of animal models of genetic obesity: comment on "Nutritional phases in
      Prader-Willi syndrome," Miller et al., 2011. Am J Med Genet Part A, 155:1040
      1049.

PMID- 22419656
TI  - Mucosal genome-wide methylation changes in inflammatory bowel disease.
AB  - BACKGROUND: DNA methylation constitutes a key epigenetic mechanism by which cells
      regulate gene transcription. Among its roles are the dynamic regulation of gene
      expression, for example, as part of an evolving immune response, and cell
      differentiation in specialized tissues. Here our aim was to study the impact of
      differences in methylation patterns in the intestine with regard to inflammatory
      bowel disease (IBD) susceptibility and activity. METHODS: Having extracted DNA
      from rectal biopsies, we conducted genome-wide methylation profiling using the
      HumanMethylation27 BeadChip microarray to identify genes showing evidence of
      differential methylation between cases of ulcerative colitis and Crohn's disease
      and healthy controls. Selected methylation signals were validated in an
      independent replication panel by pyrosequencing. Correlation with gene expression
      was sought by quantitative real-time polymerase chain reaction (RT-PCR). RESULTS:
      Multiple genes showed significant evidence of differential methylation, several
      appearing in both ulcerative colitis and Crohn's disease comparisons including
      THRAP2, FANCC, GBGT1, DOK2, TNFSF4, TNFSF12, and FUT7. Many more than expected by
      chance overlapped with genes previously implicated as playing a role in IBD
      susceptibility in genome-wide association scans, including CARD9, ICAM3, and
      IL8RB (P < 0.001). Correlation between methylation and gene expression was
      identified for selected transcripts. CONCLUSIONS: Consistent differences in DNA
      methylation between IBD cases and controls at regulatory sites within these genes
      suggest that their altered transcription contributes to IBD pathogenesis.

PMID- 22419657
TI  - Aneurysm formation after drug-eluting balloon treatment of drug-eluting in-stent
      restenosis: first case report.
AB  - A 55-year-old male underwent paclitaxel-eluting stent implantation in a
      bifurcation lesion of his left anterior descending artery (LAD) during an episode
      of unstable angina in 2008. A late in-stent restenosis developed 15 months after
      implantation of the drug-eluting stent (DES) and was treated with paclitaxel
      eluting balloon. Two months later, during angiography for functional assessment
      of the significance of lesions in the circumflex artery, an aneurysm at the place
      of drug-eluting balloon (DEB) inflation was observed. The patient was left on
      double antiplatelet therapy and scheduled for clinical observation after 3 months
      and control coronary angiography after 6 months for aneurysm progression follow
      up.

PMID- 22419658
TI  - Ultrastructural effect of self-ligating bracket materials on stainless steel and
      superelastic NiTi wire surfaces.
AB  - Frictional interactions between wires and brackets reduce the efficacy in
      orthodontic treatments. Self-ligating brackets (SLBs) are now more often used due
      to lower frictional forces when compared with conventional-ligating brackets. In
      this study, scanning electron microscopy and atomic force microscopy were used to
      examine the microstructural effects of stainless steel and ceramic SLBs on the
      surface roughness of stainless steel and superelastic NiTi wires both after in
      vivo clinical orthodontic treatment as well as in in vitro three-point bending
      experiments. A combination of two wires-0.019 in. * 0.025 in. stainless steel
      wires and 0.016 in. superelastic NiTi wires-and two SLBs-both passive-type
      stainless steel SLBs and active-type ceramic SLBs-was applied for 4 months
      (bicuspid-extraction) in an in vivo setting and for 1 month in an in vitro
      setting (200 g loads). After the SLB treatments, all wires exhibited severe
      scratches secondary to frictional interactions with the brackets. When used with
      the stainless steel SLBs (Damon 3MX(r)), the surfaces of 0.019 in. * 0.025 in.
      stainless steel (P < 0.0001) and 0.016 in. superelastic NiTi wires (P < 0.05)
      were significantly smoother than when used with the ceramic SLBs (Clippy-C(r)).
      Such results suggest that orthodontic treatments with stainless steel SLBs are
      more effective than with ceramic SLBs.

PMID- 22419659
TI  - Screening and identification of distant metastasis-related differentially
      expressed genes in human squamous cell lung carcinoma.
AB  - Distant metastasis is one of the leading causes of lung cancer death. Detecting
      the early-stage molecular alternations in primary tumors, such as gene expression
      differences, provides a "prognostic" value to the precaution of tumor metastasis.
      The aim of this article is to screen and identify the metastasis-related genes in
      human squamous cell lung carcinoma. Primary tumor tissues of nine patients with
      subsequent metastasis and eight patients without metastasis were selected to
      perform the gene microarray experiment. GO and pathway analyses were used to
      determine the differentially expressed genes. Two identified genes were further
      validated by real-time quantitative reverse transcription polymerase chain
      reaction (PCR) (real-time qRT-PCR). Two hundred and thirty-eight differentially
      expressed genes were detected in gene chip experiment, including 51 up-regulated
      genes and 187 down-regulated genes. These genes were involved in several cellular
      processes, including cell adhesion, cell cycle regulation, and apoptosis. GO
      analysis showed that the differentially expressed genes participated in a wide
      ranging of metastasis-related processes, including extracellular region and
      regulation of liquid surface tension. In addition, pathway analysis demonstrated
      that the differentially expressed genes were enriched in pathways related to cell
      cycle and Wnt signaling. Real-time qRT-PCR validation experiment of LCN2 and
      PDZK1IP1 showed a consistent up-regulation in the metastasis group. The
      metastasis of human squamous cell lung carcinoma is a complex process that is
      regulated by multiple gene alternations on the expression levels. The 238
      differentially expressed genes identified in this study presumably contain a core
      set of genes involved in tumor metastasis. The real-time qRT-PCR results of
      PDZK1IP1 and LCN2 validated the reliability of this gene microarray experiment.

PMID- 22419660
TI  - Expanding the spectrum of rearrangements involving chromosome 19: a mild
      phenotype associated with a 19p13.12-p13.13 deletion.
AB  - We report on a patient with a 1.2 Mb 19p13.12-p13.13 deletion. Compared to
      previously reported individuals with partially overlapping deletions, the
      propositus presented with a less severe phenotype, consisting of mild
      intellectual disability and behavior anomalies, with episodes of simple febrile
      seizures and without significant physical anomalies or major malformations. The
      deleted region includes 29 coding genes, some of which have already been
      demonstrated to be involved in cognitive processes. Mutations in two of them,
      CC2D1A and TECR, were recently reported to be responsible for non-syndromal,
      autosomal recessive intellectual disability. The residual alleles of all of these
      genes were submitted to sequence analysis. No sequence variants were found that
      could be considered pathogenic. This patient constitutes a further example of the
      wide phenotypic variability associated with chromosomal rearrangements, likely
      due to the different size of deleted/duplicated segments.

PMID- 22419661
TI  - Natalizumab for moderate to severe Crohn's disease in clinical practice: the Mayo
      Clinic Rochester experience.
AB  - BACKGROUND: Not all patients with Crohn's disease (CD) respond or maintain
      response to anti-tumor necrosis factor (TNF) agents and alternative treatment is
      necessary. Natalizumab, a monoclonal antibody to alpha-4 integrin approved for
      CD, has demonstrated efficacy in randomized clinical trials. We describe our
      experience with natalizumab in clinical practice at Mayo Clinic Rochester.
      METHODS: Consecutive patients prescribed natalizumab for active CD were invited
      to participate and were followed prospectively. Incidence of infection,
      hospitalization, neoplasm, or other adverse events were recorded. Clinical
      activity was assessed using the Harvey-Bradshaw Index at each 30-day infusion
      visit. RESULTS: Between April 2008 and September 2010, 36 patients were
      prescribed natalizumab and 30 (83.3%) agreed to participate. Median disease
      duration was 9 years (range, 3-43). Twenty-three patients had prior exposure to
      two anti-TNF agents, seven to one agent. All patients experienced at least one
      adverse event; none of the 13 patients in whom natalizumab was stopped (43%)
      discontinued due to adverse events. Five patients had infusions held for
      infection. No patient developed progressive multifocal leukoencephalopathy (PML).
      Fourteen patients (46%) had clinical response. The cumulative probability of
      achieving complete response within 1 year was 56% (28%-73%). Four of seven
      patients were weaned off corticosteroids. CONCLUSIONS: In our experience with
      natalizumab in clinical practice, adverse events were manageable and did not
      result in treatment cessation. No PML cases were seen and clinical response was
      similar to that in clinical trials. Natalizumab results in clinical benefit in
      patients who have active disease and have failed anti-TNF therapy.

PMID- 22419662
TI  - The effects of the renin-angiotensin-aldosterone system gene polymorphisms on
      insulin resistance in hypertensive families.
AB  - INTRODUCTION: The hereditability of insulin resistance has been demonstrated in
      both familial and twin studies. The effects of renin-angiotensin-aldosterone
      system gene polymorphisms on insulin resistance remain inconclusive. METHODS:
      This is a sibling-based association study. Polymorphisms of renin-angiotensin
      aldosterone system genes were examined in 1113 hypertension and 676 normotension
      siblings from Chinese and Japanese hypertensive families. The generalized
      estimation equations method was used to compare the differences in metabolic
      variables between hypertension and normotensive siblings. RESULTS: For the G-6A
      polymorphism of AGT, GG siblings had lower 2-h insulin than siblings carrying the
      A allele (p=0.006). Siblings with different variants of the angiotensin II type 1
      receptor A1166C had no difference in metabolic variables. Siblings carrying the D
      allele of the angiotensin converting enzyme gene had higher levels of fasting
      glucose, fasting insulin, area under the curve of insulin levels and the
      homeostasis model assessment of insulin resistance than II siblings (all p<0.05).
      Lower levels of fasting glucose and 2-h glucose were observed in siblings with
      the T allele than their CC homozygotes for the C-344T polymorphism of CYP11B2
      (p<0.05). Siblings carrying three high-risk genotypes of the angiotensin
      converting enzyme, angiotensinogen and CYP11B2 had higher fasting glucose level
      than siblings carrying no high-risk genotypes (p=0.011). CONCLUSION: Our
      comprehensive analysis of renin-angiotensin-aldosterone system gene polymorphisms
      demonstrates that the angiotensin converting enzyme and CYP11B2 gene
      polymorphisms are associated with insulin resistance in hypertensive families.

PMID- 22419663
TI  - Epidermal growth factor receptor variant III contributes to cancer stem cell
      phenotypes in invasive breast carcinoma.
AB  - EGFRvIII is a tumor-specific variant of the epidermal growth factor receptor
      (EGFR). Although EGFRvIII is most commonly found in glioblastoma, its expression
      in other tumor types remains controversial. In this study, we investigated
      EGFRvIII expression and amplification in primary breast carcinoma. Our analyses
      confirmed the presence of EGFRvIII, but in the absence of amplification or
      rearrangement of the EGFR locus. Nested reverse transcriptase PCR and flow
      cytometry were used to detect a higher percentage of positive cases. EGFRvIII
      positive cells showed increased expression of genes associated with self-renewal
      and epithelial-mesenchymal transition along with a higher percentage of stem-like
      cells. EGFRvIII also increased in vitro sphere formation and in vivo tumor
      formation. Mechanistically, EGFRvIII mediated its effects through the Wnt/beta
      catenin pathway, leading to increased beta-catenin target gene expression.
      Inhibition of this pathway reversed the observed effects on cancer stem cell
      (CSC) phenotypes. Together, our findings show that EGFRvIII is expressed in
      primary breast tumors and contributes to CSC phenotypes in breast cancer cell
      lines through the Wnt pathway. These data suggest a novel function for EGFRvIII
      in breast tumorigenesis.

PMID- 22419664
TI  - Hepatocyte-stellate cell cross-talk in the liver engenders a permissive
      inflammatory microenvironment that drives progression in hepatocellular
      carcinoma.
AB  - Many solid malignant tumors arise on a background of inflamed and/or fibrotic
      tissues, features that are found in more than 80% hepatocellular carcinomas
      (HCC). Activated hepatic stellate cells (HSC) play a critical role in
      fibrogenesis associated with HCC onset and progression, yet their functional
      impact on hepatocyte fate remains largely unexplored. Here, we used a coculture
      model to investigate the cross-talk between hepatocytes (human hepatoma cells)
      and activated human HSCs. Unsupervised genome-wide expression profiling showed
      that hepatocyte-HSC cross-talk is bidirectional and results in the deregulation
      of functionally relevant gene networks. Notably, coculturing increased the
      expression of proinflammatory cytokines and modified the phenotype of hepatocytes
      toward motile cells. Hepatocyte-HSC cross-talk also generated a permissive
      proangiogenic microenvironment, particularly by inducing VEGFA and matrix
      metalloproteinase (MMP)9 expression in HSCs. An integrative genomic analysis
      revealed that the expression of genes associated with hepatocyte-HSC cross-talk
      correlated with HCC progression in mice and was predictive of a poor prognosis
      and metastasis propensity in human HCCs. Interestingly, the effects of cross-talk
      on migration and angiogenesis were reversed by the histone deacetylase inhibitor
      trichostatin A. Our findings, therefore, indicate that the cross-talk between
      hepatoma cells and activated HSCs is an important feature of HCC progression,
      which may be targeted by epigenetic modulation.

PMID- 22419667
TI  - Heteroditopic receptors for ion-pair recognition.
AB  - Ion-pair recognition is a new field of research emerging from cation and anion
      coordination chemistry. Specific types of heteroditopic receptor designs for ion
      pairs and the complexity of ion-pair binding are discussed to illustrate key
      concepts such as cooperativity. The importance of this area of research is
      reflected by the wide variety of potential applications of ion-pair receptors,
      including applications as membrane transport and salt solubilization agents and
      sensors.

PMID- 22419666
TI  - Genome wide study of maternal and parent-of-origin effects on the etiology of
      orofacial clefts.
AB  - We performed a genome wide association analysis of maternally-mediated genetic
      effects and parent-of-origin (POO) effects on risk of orofacial clefting (OC)
      using over 2,000 case-parent triads collected through an international cleft
      consortium. We used log-linear regression models to test individual SNPs. For
      SNPs with a P-value <10(-5) for maternal genotypic effects, we also applied a
      haplotype-based method, TRIMM, to extract potential information from clusters of
      correlated SNPs. None of the SNPs were significant at the genome wide level. Our
      results suggest neither maternal genome nor POO effects play major roles in the
      etiology of OC in our sample. This finding is consistent with previous genetic
      studies and recent population-based cohort studies in Norway and Denmark, which
      showed no apparent difference between mother-to-offspring and father-to-offspring
      recurrence of clefting. We, however, cannot completely rule out maternal genome
      or POO effects as risk factors because very small effects might not be detectable
      with our sample size, they may influence risk through interactions with
      environmental exposures or may act through a more complex network of interacting
      genes. Thus, the most promising SNPs identified by this study may still be worth
      further investigation.

PMID- 22419665
TI  - Hypoxia-inducible factor-2alpha activation promotes colorectal cancer progression
      by dysregulating iron homeostasis.
AB  - Hypoxia-inducible factor (HIF), a key modulator of the transcriptional response
      to hypoxia, is increased in colon cancer. However, the role of HIF in colon
      carcinogenesis in vivo remains unclear. In this study, we found that intestinal
      epithelium-specific disruption of the von Hippel-Lindau tumor suppressor protein
      (VHL) resulted in constitutive HIF signaling, and increased HIF expression
      augmented colon tumorigenesis in the Apc(min/+) intestinal tumor model. Intestine
      specific disruption of Vhl increased colon tumor multiplicity and progression
      from adenomas to carcinomas. These effects were ameliorated in mice with double
      disruption of Vhl and HIF-2alpha. Activation of HIF signaling resulted in
      increased cell survival in normal colon tissue; however, tumor apoptosis was not
      affected. Interestingly, a robust activation of cyclin D1 was observed in tumors
      of Apc(min/+) mice in which HIF-2alpha was activated in the intestine. Consistent
      with this result, bromodeoxyuridine incorporation indicated that cellular
      proliferation was increased in colon tumors following HIF activation. Further
      analysis showed that dysregulation of the intestinal iron absorption transporter
      divalent metal transporter-1 (DMT-1) was a critical event in HIF-2alpha-mediated
      colon carcinogenesis. These data provide a mechanistic basis for the widely
      reported link between iron accumulation and colon cancer risk. Together, our
      findings show that a chronic increase in HIF-2alpha in the colon initiates
      protumorigenic signaling, which may have important implications in developing
      preventive and therapeutic strategies for colon cancer.

PMID- 22419668
TI  - GLP-1 and cardioprotection: from bench to bedside.
AB  - During myocardial infarction (MI), a variety of mechanisms contribute to the
      activation of cell death processes in cardiomyocytes, determining the final MI
      size, subsequent mortality, and post-MI remodelling. The deleterious mechanisms
      accompanying the ischaemic and reperfusion phases in MI include deprivation of
      oxygen, nutrients, and survival factors, accumulation of waste products,
      generation of oxygen free radicals, calcium overload, neutrophil infiltration of
      the ischaemic area, depletion of energy stores, and opening of the mitochondrial
      permeability transition pore, all of which contribute to the activation of
      apoptosis and necrosis in cardiomyocytes. During the last few years, glucagon
      like peptide-1 (GLP-1) (7-36)-based therapeutic strategies have been incorporated
      into the treatment of patients with type 2 diabetes mellitus. Cytoprotection is
      among the pleiotropic actions described for GLP-1 in different cell types,
      including cardiomyocytes. This paper reviews the most relevant experimental and
      clinical studies that have contributed to a better understanding of the molecular
      mechanisms and intracellular pathways involved in the cardioprotection induced by
      GLP-1, analysing in depth its potential role as a therapeutic target in the
      ischaemic and reperfused myocardium as well as in other pathologies that are
      associated with myocardial remodelling and heart failure.

PMID- 22419670
TI  - Clinical and radiological characteristics of tumefactive demyelinating lesions:
      follow-up study.
AB  - BACKGROUND: Demyelinating lesions over 20 mm in size, referred to as tumefactive
      demyelinating lesions, can be misdiagnosed as being either a tumor or an abscess.
      Although some radiological characteristics can help make a differential diagnosis
      easier, a cerebral biopsy may still be necessary. OBJECTIVE: Our objective was to
      assess the clinical characteristics of tumefactive lesions, with or without a
      diagnosis of multiple sclerosis (MS), and present follow-up data for 54 patients
      with tumefactive lesions. METHODS: Demographic, clinical, radiological and
      laboratory data were gathered and treatment responses were evaluated in a total
      of 54 patients from five medical centers. RESULT: Twenty-nine patients were
      diagnosed with tumefactive lesions at the onset, whereas 25 patients were
      diagnosed with tumefactive lesions after a diagnosis of MS. Median follow-up was
      38.12 months. At final examination, 19 of the patients with a tumefactive lesion
      diagnosis at the onset eventually developed relapsing-remitting MS, while 10
      remained with the condition as a clinically isolated syndrome. The tumefactive
      lesions studied were mostly focal, with closed-ring enhancement. We found that
      oligoclonal band positivity was less frequent in the patients with tumefactive
      onset. CONCLUSION: Although our demographic data were similar to formerly
      collected Turkish MS data, we found that the distribution of the patients'
      clinical course differed if there was an absence of primary progressive MS and
      that there was a lower frequency of secondary progressive MS cases in our group
      of patients. We believe that less frequent oligoclonal band positivity and the
      difference we witnessed in the clinical course of disease in our study groups
      suggest that there is a need for further studies to compare all the biological
      and immunological differences between MS and tumefactive lesion cases, in order
      to reveal whether there are different pathogenetic mechanisms involved.

PMID- 22419669
TI  - T-box transcription factor TBX3 reprogrammes mature cardiac myocytes into
      pacemaker-like cells.
AB  - AIM: Treatment of disorders of the sinus node or the atrioventricular node
      requires insights into the molecular mechanisms of development and homoeostasis
      of these pacemaker tissues. In the developing heart, transcription factor TBX3 is
      required for pacemaker and conduction system development. Here, we explore the
      role of TBX3 in the adult heart and investigate whether TBX3 is able to
      reprogramme terminally differentiated working cardiomyocytes into pacemaker
      cells. METHODS AND RESULTS: TBX3 expression was ectopically induced in
      cardiomyocytes of adult transgenic mice using tamoxifen. Expression analysis
      revealed an efficient switch from the working myocardial expression profile to
      that of the pacemaker myocardium. This included suppression of genes encoding gap
      junction subunits (Cx40, Cx43), the cardiac Na(+) channel (Na(V)1.5; I(Na)), and
      inwardly rectifying K(+) ion channels (K(ir) genes; I(K1)). Concordantly, we
      observed conduction slowing in these hearts and reductions in I(Na) and I(K1) in
      cardiomyocytes isolated from these hearts. The reduction in I(K1) resulted in a
      more depolarized maximum diastolic potential, thus enabling spontaneous diastolic
      depolarization. Neither ectopic pacemaker activity nor pacemaker current I(f) was
      observed. Lentiviral expression of TBX3 in ventricular cardiomyocytes resulted in
      conduction slowing and development of heterogeneous phenotypes, including
      depolarized and spontaneously active cardiomyocytes. CONCLUSIONS: TBX3
      reprogrammes terminally differentiated working cardiomyocytes and induces
      important pacemaker properties. The ability of TBX3 to reduce intercellular
      coupling to overcome current-to-load mismatch and the ability to reduce I(K1)
      density to enable diastolic depolarization are promising TBX3 characteristics
      that may facilitate biological pacemaker formation strategies.

PMID- 22419671
TI  - Arterial hypertension induced by interferon beta 1b in a patient with multiple
      sclerosis.

PMID- 22419672
TI  - Shared genetic factors may not explain the raised risk of comorbid inflammatory
      diseases in multiple sclerosis.
AB  - BACKGROUND: Comorbid inflammatory conditions in multiple sclerosis (MS) patients
      suggest shared risks with MS. OBJECTIVE: To estimate if the risk of immune
      mediated disease in MS patients and their parents is increased. METHODS: Swedish
      register data were analysed using Cox regression to estimate immune-mediated
      disease risk among 11284 fathers and 12006 mothers of MS patients, compared with
      123158 fathers and 129409 mothers of index subjects without MS. Similar analyses
      were conducted among 20276 index subjects with MS and 203951 without. RESULTS:
      Parents of patients with MS did not have a significantly altered immune-mediated
      disease risk. Patients with MS had a consistently raised risk for several immune
      mediated diseases: ulcerative colitis, Crohn's disease, type 1 diabetes,
      psoriasis, polyarthritis nodosa and pemphigoid. The risk was more pronounced for
      diseases diagnosed subsequent to MS onset. CONCLUSION: The increased occurrence
      of other immune-mediated diseases in MS patients may not be due to shared genetic
      factors and surveillance bias is likely to be the main or possibly the entire
      explanation. If not entirely explained by surveillance bias, a modestly raised
      occurrence of comorbid diseases may be due to shared environmental risks or
      factors related to MS disease characteristics.

PMID- 22419673
TI  - Inflammation inhibits GABA transmission in multiple sclerosis.
AB  - Abnormal glutamate-dependent synaptic excitation contributes to neuronal damage
      in multiple sclerosis (MS). Little is known about the involvement of the GABA
      system in this disorder. Here we found that cerebrospinal fluid (CSF) from MS
      patients with enhanced brain lesions on magnetic resonance imaging inhibited GABA
      transmission in mouse brain slices. Enhanced IL-1beta neuronal action was
      responsible for this effect, because IL-1beta receptor antagonist blocked, and
      exogenous IL-1beta mimicked the synaptic effect of inflamed CSF. Our results
      provide evidence that focal inflammation in MS perturbs the cytokine milieu
      within the circulating CSF, resulting in diffuse GABAergic alteration in neurons.

PMID- 22419674
TI  - Cognitive impairment is associated with reduced bone mass in multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) has been associated with reduced bone mineral
      density (BMD), yet the underlying causes are not fully known. The recent
      discovery that bone homeostasis is directly regulated by the brain led us to
      hypothesize that it may be impaired by MS pathology. As cognitive impairment (CI)
      is a well-documented correlate of MS-related brain pathology, we tested the
      hypothesis that it is associated with reduced BMD. OBJECTIVE: We aimed to
      determine if CI is associated with reduced BMD in patients with MS. METHODS: We
      retrospectively studied the medical records of 56 patients with MS, <=50 years
      old, with Expanded Disability Status Scale score <=4.5 and with dual X-ray
      absorptiometry (DEXA) BMD measurement within 1 year of neuropsychological testing
      with a standard battery (MACFIMS). RESULTS: In total, 23 (41.1%) MS patients had
      osteopenia or osteoporosis. Mean femur BMD was significantly lower in patients
      with MS with CI (0.89+/-0.12 g/cm(2)) compared with intact patients (0.99+/-0.17
      g/cm(2), p=0.009). In the cognitively impaired group, 59.3% had either osteopenia
      or osteoporosis, compared with 24.1% in the non-cognitively impaired group (odds
      ratio=4.57, p=0.008). CONCLUSION: CI is associated with reduced BMD in patients
      with MS, suggesting that central mechanisms involved in bone homeostasis may be
      directly impaired by MS-related inflammatory and neurodegenerative processes.

PMID- 22419675
TI  - Specificity of the tuberculin skin test is modified by use of a protein cocktail
      containing ESAT-6 and CFP-10 in cattle naturally infected with Mycobacterium
      bovis.
AB  - The mycobacterial immunodominant ESAT-6 and CFP-10 antigens are strongly
      recognizable in tuberculosis-infected cattle, and they do not elicit a response
      in cattle without infection. In addition, they are absent in most environmental
      mycobacterial species, and therefore, their use can be an alternative to purified
      protein derivative (PPD) tuberculin in the development of a more specific skin
      diagnostic test in cattle. The aim of the current study was to assess the
      potential of an ESAT-6 and CFP-10 (E6-C10) protein cocktail in a skin test format
      in naturally tuberculosis-infected and paratuberculosis-infected cattle. We also
      included MPB83 as a third component in one of the protein cocktail preparations.
      The protein cocktail was tested at different dose concentrations (5, 10, and 15
      MUg per protein). The best skin response to the E6-C10 protein cocktail was
      obtained with 10 MUg. Subsequently, this concentration was tested in 2 herds with
      high and low bovine tuberculosis prevalence, the latter with paratuberculosis
      coinfection. Our data show that the E6-C10 cocktail allows identification of an
      important proportion of animals that PPDB is not able to recognize, especially in
      low-prevalence herds. The protein cocktail did not induce reactions in
      tuberculosis-free cattle or in paratuberculosis-infected cattle. Addition of
      MPB83 to the protein cocktail did not make any difference in the skin reaction.

PMID- 22419676
TI  - Induction of protective immune responses by a multiantigenic DNA vaccine encoding
      GRA7 and ROP1 of Toxoplasma gondii.
AB  - Toxoplasma gondii is distributed worldwide and infects most species of warm
      blooded animals, including humans. The heavy incidence and severe or lethal
      damage caused by T. gondii infection clearly indicates the need for the
      development of a vaccine. To evaluate the protective efficacy of a multiantigenic
      DNA vaccine expressing GRA7 and ROP1 of T. gondii with or without a plasmid
      encoding murine interleukin-12 (pIL12), we constructed DNA vaccines using the
      eukaryotic plasmids pGRA7, pROP1, and pGRA7-ROP1. Mice immunized with pGRA7,
      pROP1, or pGRA7-ROP1 showed significantly increased serum IgG2a titers;
      production of gamma interferon (IFN-gamma), IL-10, and tumor necrosis factor
      alpha (TNF-alpha); in vitro T cell proliferation; and survival, as well as
      decreased cyst burdens in the brain, compared to mice immunized with either the
      empty plasmid, pIL12, or vector with pIL12 (vector+pIL12). Moreover, mice
      immunized with the multiantigenic DNA vaccine pGRA7-ROP1 had higher IgG2a titers,
      production of IFN-gamma and TNF-alpha, survival time, and cyst reduction rate
      compared to those of mice vaccinated with either pGRA7 or pROP1 alone.
      Furthermore, mice immunized with either a pGRA7-ROP1+pIL12 or a single-gene
      vaccine combined with pIL12 showed greater Th1 immune response and protective
      efficacy than the single-gene-vaccinated groups. Our data suggest that the
      multiantigenic DNA antigen pGRA7-ROP1 was more effective in stimulating host
      protective immune responses than separately injected single antigens, and that IL
      12 serves as a good DNA adjuvant.

PMID- 22419677
TI  - Congruence between preferred and actual place of care and death among Danish
      cancer patients.
AB  - BACKGROUND: Meeting patient's preferences is an important outcome in palliative
      care. No Scandinavian study has reported systematically collected preferences
      from patients regarding place of care (POC) and place of death (POD). The extent
      of possible incongruence between patients' preferences and reality remains
      unknown. AIM: The aim of this study was to describe patients' preferred POC and
      POD and changes in preferences over time and to evaluate congruence between
      preferences and reality. Furthermore, the aim was to search for predictive
      factors regarding patients' wishes and fulfilment of these. METHOD: This is a
      prospective interview and questionnaire study. SETTING/PARTICIPANTS: The study
      was conducted in the former Aarhus County, Denmark and 96 end-stage cancer
      patients participated. RESULTS: Of the patients, who stated a preference, 84%
      preferred home care and 71% preferred home death. A positive association between
      living with a partner and both wishing for home care and home death was observed
      (prevalence ratio (PR): 1.66 (95% confidence intervals (CI): 1.07, 2.58), p =
      0.02 and PR: 2.33 (95% CI: 1.14, 4.77), p = 0.02, respectively). Marked changes
      in preferences were observed. Overall, preferences were met for approximately
      half of the patients, although kappa values were low (kappa=0.132 for POC and
      kappa=0.034 for POD).We found a significant association between being cared for
      in the preferred place and having contact with a palliative care team (PR: 2.01
      (95% CI: 1.02, 3.98), p = 0.045). CONCLUSION: Regular discussions with patients
      on this subject are needed. Social and professional support is of importance in
      meeting patients' preferences. Larger scaled studies and research focusing on
      meeting patients' preferences are needed.

PMID- 22419678
TI  - Development of simultaneous pitch encoding: infants show a high voice superiority
      effect.
AB  - Infants must learn to make sense of real-world auditory environments containing
      simultaneous and overlapping sounds. In adults, event-related potential studies
      have demonstrated the existence of separate preattentive memory traces for
      concurrent note sequences and revealed perceptual dominance for encoding of the
      voice with higher fundamental frequency of 2 simultaneous tones or melodies.
      Here, we presented 2 simultaneous streams of notes (15 semitones apart) to 7
      month-old infants. On 50% of trials, either the higher or the lower note was
      modified by one semitone, up or down, leaving 50% standard trials. Infants showed
      mismatch negativity (MMN) to changes in both voices, indicating separate memory
      traces for each voice. Furthermore, MMN was earlier and larger for the higher
      voice as in adults. When in the context of a second voice, representation of the
      lower voice was decreased and that of the higher voice increased compared with
      when each voice was presented alone. Additionally, correlations between MMN
      amplitude and amount of weekly music listening suggest that experience affects
      the development of auditory memory. In sum, the ability to process simultaneous
      pitches and the dominance of the highest voice emerge early during infancy and
      are likely important for the perceptual organization of sound in realistic
      environments.

PMID- 22419679
TI  - The modulation of BOLD variability between cognitive states varies by age and
      processing speed.
AB  - Increasing evidence suggests that brain variability plays a number of important
      functional roles for neural systems. However, the relationship between brain
      variability and changing cognitive demands remains understudied. In the current
      study, we demonstrate experimental condition-based modulation in brain
      variability using functional magnetic resonance imaging. Within a sample of
      healthy younger and older adults, we found that blood oxygen level-dependent
      signal variability was an effective discriminator between fixation and external
      cognitive demand. Across a number of regions, brain variability increased broadly
      on task compared with fixation, particularly in younger and faster performing
      adults. Conversely, older and slower performing adults exhibited fewer changes in
      brain variability within and across experimental conditions and brain regions,
      indicating a reduction in variability-based neural specificity. Increases in
      brain variability on task may represent a more complex neural system capable of
      greater dynamic range between brain states, as well as an enhanced ability to
      efficiently process varying and unexpected external stimuli. The current results
      help establish the developmental and performance correlates of state-to-state
      brain variability-based transitions and offer a new line of inquiry in the study
      of rest versus task modes in the human brain.

PMID- 22419680
TI  - Preparatory attention relies on dynamic interactions between prelimbic cortex and
      anterior cingulate cortex.
AB  - An emerging view of prefrontal cortex (PFC) function is that multiple PFC areas
      process information in parallel, rather than as distinct modules. Two key
      functions assigned to the PFC are the regulation of top-down attention and
      stimulus-guided action. Electrophysiology and lesion studies indicate the
      involvement of both the anterior cingulate cortex (ACC) and prelimbic cortex (PL)
      in these functions. Little is known, however, about how these cortical regions
      interact. We recorded single unit spiking and local field potentials (LFPs)
      simultaneously in rodents during a sustained attention task and assessed
      interactions between the ACC and PL by measuring spike-LFP phase synchrony and
      LFP-LFP phase synchrony between these areas. We demonstrate that the magnitude of
      synchrony between the ACC and PL, before stimulus onset, predicts the subjects'
      behavioral choice after the stimulus. Furthermore, neurons switched from a state
      of beta synchrony during attention to a state of delta synchrony before the
      instrumental action. Our results indicate that multiple PFC areas interact during
      attention and that the same neurons may participate in segregated assemblies that
      support both attention and action.

PMID- 22419681
TI  - Escherichia coli bloodstream infection after transrectal ultrasound-guided
      prostate biopsy: implications of fluoroquinolone-resistant sequence type 131 as a
      major causative pathogen.
AB  - BACKGROUND: Transrectal ultrasound-guided (TRUS) prostate biopsy is a commonly
      performed procedure, and fluoroquinolones are the most frequently given
      prophylactic antimicrobials. In the context of increasing fluoroquinolone
      resistance, and the international emergence of fluoroquinolone-resistant sequence
      type 131 (ST131) Escherichia coli, we describe a large series of E. coli
      bacteremia after TRUS biopsy. METHODS: All male patients admitted with community
      onset (CO) E. coli bacteremia from January 2006 through December 2010 were
      included. Patient characteristics, treatment outcomes, and rates of antimicrobial
      resistance were compared between patients with TRUS biopsy-related bacteremia and
      other male patients with CO E. coli bacteremia. Molecular typing was performed on
      E. coli isolates to determine phylogenetic group. RESULTS: A total of 258 male
      patients were admitted with CO E. coli bacteremia. Of these, 47 patients (18%)
      were admitted after TRUS biopsy. Patients who had undergone TRUS biopsy were
      twice as likely to require intensive care admission (25% vs 12%) and had
      significantly higher rates of resistance to gentamicin (43%), trimethoprim
      sulphamethoxazole (60%), and ciprofloxacin (62%) as well as all 3 agents in
      combination (19%). Thirty-six percent of post-TRUS biopsy patients did not
      receive active empirical antibiotic therapy. The ST131 clone accounted for 41% of
      all E. coli isolates after TRUS biopsy. CONCLUSIONS: E. coli bacteremia can be a
      life-threatening complication of TRUS biopsy. Infecting strains are frequently
      multidrug-resistant and resistant to common empirical antibiotic agents. E. coli
      ST131 is an important cause of sepsis after TRUS biopsy. Further studies should
      evaluate colonization with fluoroquinolone-resistant E. coli as a risk factor for
      postbiopsy sepsis.

PMID- 22419682
TI  - Verification bias in a diagnostic accuracy study of symptom screening for
      tuberculosis in HIV-infected pregnant women.

PMID- 22419684
TI  - It is time to change the paradigm for hepatitis C virus testing.

PMID- 22419689
TI  - In mpkCCD cells, long-term regulation of aquaporin-2 by vasopressin occurs
      independent of protein kinase A and CREB but may involve Epac.
AB  - Urine concentration involves the hormone vasopressin (AVP), which stimulates cAMP
      production in renal principal cells, resulting in translocation and transcription
      of aquaporin-2 (AQP2) water channels, greatly increasing the water permeability,
      leading to a concentrated urine. As cAMP levels decrease shortly after AVP
      addition, whereas AQP2 levels still increase and are maintained for days, we
      investigated in the present study the mechanism responsible for the AQP2 increase
      after long-term 1-desamino-8-d-arginine vasopressin (dDAVP) application using
      mouse collecting duct (mpkCCD) cells. While 30 min of dDAVP incubation strongly
      increased cAMP, cAMP was lower with 1 day and was even further reduced with 4
      days of dDAVP, although still significantly higher than in control cells. One day
      of dDAVP incubation increased AQP2 promoter-dependent transcription, which was
      blocked by the protein kinase A (PKA) inhibitor H89. Moreover, phosphorylation of
      the cAMP-responsive element binding protein (CREB) and CRE-dependent
      transcription was observed after short-term dDAVP stimulation. With 4 days of
      dDAVP, AQP2 transcription remained elevated, but this was not blocked by H89, and
      CRE-dependent transcription and CREB phosphorylation were not increased. Exchange
      factor directly activated by cAMP (Epac) 1 and 2 were found to be endogenously
      expressed in mpkCCD cells. Application of dDAVP increased the expression of
      Epac1, while Epac2 was reduced. Incubation with a specific Epac activator after
      dDAVP pretreatment increased both AQP2 abundance and transcription compared with
      cells left unstimulated the last day. In conclusion, the PKA-CRE pathway is
      involved in the initial rise in AQP2 levels after dDAVP stimulation but not in
      the long-term effect of dDAVP. Instead, long-term regulation of AQP2 may involve
      the activation of Epac.

PMID- 22419690
TI  - Renal tubular fluid shear stress facilitates monocyte activation toward
      inflammatory macrophages.
AB  - Modified urinary fluid shear stress (FSS) induced by variations of urinary fluid
      flow and composition is observed in early phases of most kidney diseases.
      Recently, we reported that renal tubular FSS promotes endothelial cell activation
      and subsequent adhesion of human monocytes, thereby suggesting that changes in
      urinary FSS can induce the development of inflammation (Miravete M, Klein J,
      Besse-Patin A, Gonzalez J, Pecher C, Bascands JL, Mercier-Bonin M, Schanstra JP,
      Buffin-Meyer B, BBRC 407: 813-817, 2011). Here, we evaluated the influence of
      tubular FSS on monocytes as they play an important role in the progression of
      inflammation in nephropathies. Human renal tubular cells (HK-2) were exposed to
      FSS 0.01 Pa for 30 min or 5 h. Treatment of human THP-1 monocytes with the
      resulting conditioned medium (FSS-CM) modified the expression of macrophage
      differentiation markers, suggesting differentiation toward the inflammatory M1
      type macrophage. The effect was confirmed in freshly isolated human monocytes. In
      contrast to endothelial cells, the activation of monocytes by FSS-CM did not
      require TNF-alpha. Cytokine array analysis of FSS-CM showed that FSS modified
      secretion of cytokines by HK-2 cells, particularly by increasing secretion of TGF
      beta and by decreasing secretion of C-C chemokine ligand 2 (CCL2). Neutralization
      of TGF-beta or CCL2 supplementation attenuated the effect of FSS-CM on macrophage
      differentiation. Finally, FSS-injured HK-2 cells expressed and secreted early
      biomarkers of tubular damage such as kidney injury molecule 1 and neutrophil
      gelatinase-associated lipocalin. In conclusion, changes in urinary FSS should now
      also be considered as potential insults for tubular cells that
      initiate/perpetuate interstitial inflammation.

PMID- 22419691
TI  - Mammalian target of rapamycin and the kidney. I. The signaling pathway.
AB  - The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays
      a fundamental role in regulating cellular homeostasis and metabolism. In a two
      part review, we examine the complex molecular events involved in the regulation
      and downstream effects of mTOR, as well as the pivotal role played by this kinase
      in many renal diseases, particularly acute kidney injury, diabetic nephropathy,
      and polycystic kidney diseases. Here, in the first part of the review, we provide
      an overview of the complex signaling events and pathways governing mTOR activity
      and action. mTOR is a key component of two multiprotein complexes, known as mTOR
      complex 1 (mTORC1) and 2 (mTORC2). Some proteins are found in both mTORC1 and
      mTORC2, while others are unique to one or the other complex. Activation of mTORC1
      promotes cell growth (increased cellular mass or size) and cell proliferation
      (increased cell number). mTORC1 acts as a metabolic "sensor," ensuring that
      conditions are optimal for both cell growth and proliferation. Its activity is
      tightly regulated by the availability of amino acids, growth factors, energy
      stores, and oxygen. The effects of mTORC2 activation are distinct from those of
      mTORC1. Cellular processes modulated by mTORC2 include cell survival, cell
      polarity, cytoskeletal organization, and activity of the aldosterone-sensitive
      sodium channel. Upstream events controlling mTORC2 activity are less well
      understood than those controlling mTORC1, although growth factors appear to
      stimulate both complexes. Rapamycin and its analogs inhibit the activity of
      mTORC1 only, and not that of mTORC2, while the newer "catalytic" mTOR inhibitors
      affect both complexes.

PMID- 22419693
TI  - In pursuit of scientific excellence: sex matters.

PMID- 22419692
TI  - Addition of endothelial progenitor cells to renal revascularization restores
      medullary tubular oxygen consumption in swine renal artery stenosis.
AB  - Renal artery stenosis (RAS) promotes microvascular rarefaction and fibrogenesis,
      which may eventuate in irreversible kidney injury. We have shown that
      percutaneous transluminal renal angioplasty (PTRA) or endothelial progenitor
      cells (EPC) improve renal cortical hemodynamics and function in the poststenotic
      kidney. The renal medulla is particularly sensitive to hypoxia, yet little is
      known about reversibility of medullary injury on restoration of renal blood flow.
      This study was designed to test the hypothesis that PTRA, with or without adjunct
      EPC delivery to the stenotic kidney, may improve medullary remodeling and tubular
      function. RAS was induced in 21 pigs using implantation of irritant coils, while
      another group served as normal controls (n = 7 each). Two RAS groups were then
      treated 6 wk later with PTRA or both PTRA and EPC. Four weeks later, medullary
      hemodynamics, microvascular architecture, and oxygen-dependent tubular function
      of the stenotic kidneys were examined using multidetector computed tomography,
      microcomputed tomography, and blood oxygenation level-dependent MRI,
      respectively. Medullary protein expression of vascular endothelial growth factor,
      endothelial nitric oxide synthase, hypoxia-inducible factor-1alpha, and NAD(P)H
      oxidase p47 were determined. All RAS groups showed decreased medullary vascular
      density and blood flow. However, in RAS+PTRA+EPC animals, EPC were engrafted in
      tubular structures, oxygen-dependent tubular function was normalized, and
      fibrosis attenuated, despite elevated expression of hypoxia-inducible factor
      1alpha and sustained downregulation of vascular endothelial growth factor. In
      conclusion, EPC delivery, in addition to PTRA, restores medullary oxygen
      dependent tubular function, despite impaired medullary blood and oxygen supply.
      These results support further development of cell-based therapy as an adjunct to
      revascularization of RAS.

PMID- 22419694
TI  - MicroRNA-126 contributes to renal microvascular heterogeneity of VCAM-1 protein
      expression in acute inflammation.
AB  - Endothelial cells in different microvascular segments of the kidney have diverse
      functions and exhibit differential responsiveness to disease stimuli. The
      responsible molecular mechanisms are largely unknown. We previously showed that
      during hemorrhagic shock, VCAM-1 protein was expressed primarily in
      extraglomerular compartments of the kidney, while E-selectin protein was highly
      induced in glomeruli only (van Meurs M, Wulfert FM, Knol AJ, de Haes A,
      Houwertjes M, Aarts LPHJ, Molema G. Shock 29: 291-299, 2008). Here, we
      investigated the molecular control of expression of these endothelial cell
      adhesion molecules in mouse models of renal inflammation. Microvascular segment
      specific responses to the induction of anti-glomerular basement membrane (anti
      GBM), glomerulonephritis and systemic TNF-alpha treatment showed that E-selectin
      expression was transcriptionally regulated, with high E-selectin mRNA and protein
      levels preferentially expressed in the glomerular compartment. In contrast, VCAM
      1 mRNA expression was increased in both arterioles and glomeruli, while VCAM-1
      protein expression was limited in the glomeruli. These high VCAM-1 mRNA/low VCAM
      1 protein levels were accompanied by high local microRNA (miR)-126 and Egfl7
      levels, as well as higher Ets1 levels compared with arteriolar expression levels.
      Using miR-reporter constructs, the functional activity of miR-126 in glomerular
      endothelial cells could be demonstrated. Moreover, in vivo knockdown of miR-126
      function unleashed VCAM-1 protein expression in the glomeruli upon inflammatory
      challenge. These data imply that miR-126 has a major role in the segmental,
      heterogenic response of renal microvascular endothelial cells to systemic
      inflammatory stimuli.

PMID- 22419695
TI  - Developmental expression of renal organic anion transporters in rat kidney and
      its effect on renal secretion of phenolsulfonphthalein.
AB  - Organic anion transporters (OAT1 and OAT3) and multidrug resistance-associated
      proteins (MRP2 and MRP4) play important roles in anionic drug secretion in renal
      proximal tubules. Changes in the expression of such transporters are considered
      to affect the tubular secretion of anionic drugs. The purpose of this study was
      to elucidate the developmental changes in the expression of OAT1, OAT3, MRP2, and
      MRP4 and their effects on the tubular secretion of drugs. The mRNA level of each
      transporter was measured by real-time PCR, and the protein expression was
      evaluated by Western blotting and immunohistochemical analysis. In addition, the
      tubular secretion of phenolsulfonphthalein (PSP) in infant (postnatal day 14) and
      adult rats was estimated based on in vivo clearance study. The protein expression
      of organic anion transporters were very low at postnatal day 0 and gradually
      increased with age. In postnatal day 14 rats, the expression of OAT1 and OAT3
      seemed to be at almost mature levels, while MRP2 and MRP4 seemed to be at
      immature levels. Immunohistochemical analysis in the kidney of postnatal day 0
      rats revealed OATs on the basolateral membrane and MRPs on the brush-border
      membrane. At postnatal day 0, the distribution of these transporters was
      restricted to the inner cortical region, while after postnatal day 14, it was
      identical to that in adult kidney. An in vivo clearance study revealed that the
      tubular secretion of PSP was significantly lower in postnatal day 14 rats than
      adult rats. These results indicate that age-dependent changes in organic anion
      transporter expression affect the tubular secretion of anionic drugs in pediatric
      patients.

PMID- 22419696
TI  - Sustained-release prostacyclin analog ONO-1301 ameliorates tubulointerstitial
      alterations in a mouse obstructive nephropathy model.
AB  - Tubulointerstitial injuries are crucial histological alterations that predict the
      deterioration of renal function in chronic kidney disease. ONO-1301, a novel
      sustained-release prostacyclin analog, accompanied by thromboxane synthase
      activity, exerts therapeutic effects on experimental pulmonary hypertension, lung
      fibrosis, cardiomyopathy, and myocardial ischemia, partly associated with the
      induction of hepatocyte growth factor (HGF). In the present study, we examined
      the therapeutic efficacies of ONO-1301 on tubulointerstitial alterations induced
      by unilateral ureteral obstruction (UUO). After inducing unilateral ureteral
      obstruction in C57/BL6J mice, a single injection of sustained-release ONO-1301
      polymerized with poly (D,L-lactic-co-glycolic acid) sustained-release ONO-1301
      (SR-ONO) significantly suppressed interstitial fibrosis, accumulation of types I
      and III collagen, increase in the number of interstitial fibroblast-specific
      protein-1 (FSP-1)(+) cells, and interstitial infiltration of
      monocytes/macrophages (F4/80(+)) in the obstructed kidneys (OBK; day 7).
      Treatment with SR-ONO significantly suppressed the increase of the renal levels
      of profibrotic factor TGF-beta and phosphorylation of Smad2/3, and elevated the
      renal levels of HGF in the OBK. In cultured mouse proximal tubular epithelial
      cells (mProx24), ONO-1301 significantly ameliorated the expression of fibroblast
      specific protein-1 and alpha-smooth muscle actin as well as phosphorylation of
      Smad3 and increased the expression of zonula occludens-1 and E-cadherin in the
      presence of TGF-beta1 as detected by immunoblot and immunocytochemistry, partly
      dependent on PGI(2) receptor-mediated signaling. Administration of rabbit anti
      HGF antibodies, but not the control IgG, partly reversed the suppressive effects
      of SR-ONO on tubulointerstitial injuries in the OBK. Taken together, our findings
      suggest the potential therapeutic efficacies of ONO-1301 in suppressing
      tubulointerstitial alterations partly mediated via inducing HGF, an antifibrotic
      factor counteracting TGF-beta.

PMID- 22419698
TI  - Relationships among race, bleeding, and mortality in coronary reperfusion.

PMID- 22419697
TI  - Impaired myogenic constriction of the renal afferent arteriole in a mouse model
      of reduced betaENaC expression.
AB  - Previous studies demonstrate a role for beta epithelial Na(+) channel (betaENaC)
      protein as a mediator of myogenic constriction in renal interlobar arteries.
      However, the importance of betaENaC as a mediator of myogenic constriction in
      renal afferent arterioles, the primary site of development of renal vascular
      resistance, has not been determined. We colocalized betaENaC with smooth muscle
      alpha-actin in vascular smooth muscle cells in renal arterioles using
      immunofluorescence. To determine the importance of betaENaC in myogenic
      constriction in renal afferent arterioles, we used a mouse model of reduced
      betaENaC (betaENaC m/m) and examined pressure-induced constrictor responses in
      the isolated afferent arteriole-attached glomerulus preparation. We found that,
      in response to a step increase in perfusion pressure from 60 to 120 mmHg, the
      myogenic tone increased from 4.5 +/- 3.7 to 27.3 +/- 5.2% in +/+ mice. In
      contrast, myogenic tone failed to increase with the pressure step in m/m mice
      (3.9 +/- 0.8 to 6.9 +/- 1.4%). To determine the importance of betaENaC in
      myogenic renal blood flow (RBF) regulation, we examined the rate of change in
      renal vascular resistance following a step increase in perfusion pressure in
      volume-expanded animals. We found that, following a step increase in pressure,
      the rate of myogenic correction of RBF is inhibited by 75% in betaENaC m/m mice.
      These findings demonstrate that myogenic constriction in afferent arterioles is
      dependent on normal expression of betaENaC.

PMID- 22419699
TI  - Association of bleeding and in-hospital mortality in black and white patients
      with st-segment-elevation myocardial infarction receiving reperfusion.
AB  - BACKGROUND: Prior studies have suggested that blacks with acute ST-segment
      elevation myocardial infarction have increased bleeding risks with fibrinolysis
      relative to whites, yet these data were quite limited. Additionally, it is
      unknown whether there are racial differences in bleeding risks among patients
      with ST-segment-elevation myocardial infarction receiving primary percutaneous
      coronary intervention. METHODS AND RESULTS: We evaluated data on blacks and
      whites with ST-segment-elevation myocardial infarction treated with either
      fibrinolysis or primary percutaneous coronary intervention from the National
      Registry of Myocardial Infarction (NRMI)-4 and 5 participating centers between
      July 2000 and December 2006. We compared differences between the 2 groups in
      rates of in-hospital major bleeding and mortality, adjusted with logistic
      regression analyses. In fibrinolytic-treated patients with ST-segment-elevation
      myocardial infarction, the bleeding rates were higher among blacks (n=2283) than
      whites (n=42 243; 10.9% versus 10.3%; adjusted odds ratio, 1.21; 95% confidence
      interval, 1.02-1.43). Similarly, in patients receiving primary percutaneous
      coronary intervention, the bleeding rates were higher in blacks (n=2826) than in
      whites (n=46 332; 10.3% versus 7.8%; adjusted odds ratio, 1.33; 95% confidence
      interval, 1.13-1.56). Bleeding was associated with higher risk of death in both
      ethnic groups. However, there was no overall racial difference in in-hospital
      mortality among those with bleeding or without bleeding treated with either
      fibrinolysis or primary percutaneous coronary intervention. CONCLUSIONS: Blacks
      with ST-segment-elevation myocardial infarction treated with either fibrinolysis
      or primary percutaneous coronary intervention had a higher risk of bleeding
      events than their white counterparts. Bleeding was associated with a similar
      increased risk of death in both ethnic groups treated by either reperfusion
      strategy.

PMID- 22419700
TI  - Anaplastic thyroid carcinoma with cutaneous extension.

PMID- 22419701
TI  - Absence of mutation in coding regions of CYP2R1 gene in apparent autosomal
      dominant vitamin D 25-hydroxylase deficiency rickets.
AB  - CONTEXT: This is a case report of a proband and his family presenting with
      apparent autosomal dominant 25-hydroxylase enzyme deficiency and bone disease.
      OBJECTIVE: The aim of the study was to present an alternative pattern of
      transmission of 25-hydroxylase enzyme deficiency other than autosomal recessive.
      DESIGN: We diagnosed our patient with 25-hydroxylase enzyme deficiency, treated
      him, and examined his DNA for mutations. Evaluations at other institutions,
      clinical history of all family members, and laboratory testing for the mother,
      aunt, and maternal grandmother were reviewed. Family consent was obtained for all
      testing and record review. SETTING: The patient was evaluated serially in an
      outpatient clinic. Routine laboratory studies for proband, mother, and maternal
      grandmother were obtained. Genetic testing was performed in another institution
      after obtaining family consent. INTERVENTIONS: No research intervention was
      performed. MAIN OUTCOME MEASURES: Routine clinical care included an evaluation of
      growth pattern. Laboratory evaluation included 25-hydroxyvitamin D, 1,25
      dihydroxyvitamin D [1,25(OH)(2)D], alkaline phosphatase, intact PTH, phosphate,
      calcium, ionized calcium, and magnesium levels. RESULTS: Results showed
      consistently low 25-hydroxylase enzyme function. They also showed elevated
      alkaline phosphatase and PTH, as well as decreased phosphate and calcium. These
      abnormalities were corrected with 1,25(OH)(2)D therapy. CONCLUSION: We conclude
      that 25-hydroxylase enzyme deficiency can be inherited in an autosomal dominant
      pattern. This case raises a question about different tributary pathways affecting
      the function of the 25-hydroxylase enzyme. Physiological dosing of 1,25(OH)(2)D
      was sufficient for treatment. There were no detectable mutations in any of the
      coding regions of the gene or its intronic junctions.

PMID- 22419702
TI  - Metformin improves pregnancy and live-birth rates in women with polycystic ovary
      syndrome (PCOS): a multicenter, double-blind, placebo-controlled randomized
      trial.
AB  - BACKGROUND: The role of metformin in the treatment of infertility in women with
      polycystic ovary syndrome (PCOS) is still controversial. OBJECTIVE AND OUTCOMES:
      We investigated whether metformin decreases the early miscarriage rate and
      improves the pregnancy rates (PR) and live-birth rates (LBR) in PCOS. METHODS:
      This was a multicenter, randomized (1:1), double-blind, placebo-controlled study.
      Three hundred twenty women with PCOS and anovulatory infertility were randomized
      to metformin (n = 160, Diformin; obese women, 1000 mg two times daily; nonobese
      subjects, 500 mg + 1000 mg daily) or identical doses of placebo (n = 160). After
      3 months' treatment, another appropriate infertility treatment was combined if
      necessary. If pregnancy occurred, metformin/placebo was continued up to the 12th
      week. RESULTS: Miscarriage rates were low and similar in the two groups
      (metformin 15.2% vs. placebo 17.9%, P = 0.8). Intent-to-treat analysis showed
      that metformin significantly improved PR and LBR (vs. placebo) in the whole study
      population (PR: 53.6 vs. 40.4%, P = 0.006; LBR: 41.9 vs. 28.8%, P = 0.014) and PR
      in obese women (49.0 vs. 31.4%, P = 0.04), and there was a similar trend in
      nonobese (PR: 58.6 vs. 47.6%, P = 0.09; LBR: 46.7 vs. 34.5%, P = 0.09) and in
      obese women with regard to LBR (35.7 vs. 21.9%, P = 0.07). Cox regression
      analysis showed that metformin plus standard infertility treatment increased the
      chance of pregnancy 1.6 times (hazard rate 1.6, 95% confidence interval 1.13
      2.27). CONCLUSION: Obese women especially seem to benefit from 3 months'
      pretreatment with metformin and its combination thereafter with routine ovulation
      induction in anovulatory infertility.

PMID- 22419703
TI  - TMEM127 screening in a large cohort of patients with pheochromocytoma and/or
      paraganglioma.
AB  - CONTEXT: TMEM127 is a novel pheochromocytoma (PCC) susceptibility gene.
      OBJECTIVES: Our aim was to clearly determine the indications for TMEM127 genetic
      testing in patients with PCC and/or paraganglioma (PGL). PATIENTS AND METHODS:
      Germline DNA from 642 unrelated patients who did not carry mutations in major PCC
      susceptibility genes was analyzed. Five hundred fifty-nine patients were affected
      by PCC, 72 by PGL (22 with head and neck and 50 with thoracic or abdominal
      location), and 11 by both PCC and PGL. Analysis of the TMEM127 gene was performed
      by direct sequencing and quantitative multiplex PCR of short fluorescent
      fragments. RESULTS: In our cohort six mutations (0.9%) were identified. Three of
      them (p.Ala47Asp, p.Gln64HisfsX18, p.Tyr164X) were found in patients exhibiting
      clinical criteria for a hereditary disease (young age at diagnosis, bilateral
      PCC, or family history). The three others (p.Gln157X, p.Val68SerfsX13,
      p.Val90Met) were detected in patients with an apparently sporadic presentation.
      No mutation was found among patients with PGL, and no large chromosomal
      rearrangement spanning the TMEM127 gene was detected. CONCLUSIONS: Our results
      combined with the two previous studies suggest that direct sequencing of TMEM127
      should be considered, after a negative screening of VHL, RET, SDHB, and SDHD
      genes, in patients with PCC.

PMID- 22419704
TI  - Autologous hematopoietic stem cell transplantation modulates immunocompetent
      cells and improves beta-cell function in Chinese patients with new onset of type
      1 diabetes.
AB  - CONTEXT: Autologous hematopoietic stem cell transplantation (AHSCT) has the
      potential to induce clinical remission in patients with newly diagnosed type 1
      diabetes. OBJECTIVE: The objective of the study was to examine the impact of
      AHSCT on lymphocytes and pancreatic beta-cell function. DESIGN: This was a
      nonrandomized, open-label prospective study. PATIENTS AND INTERVENTIONS: Thirteen
      patients with new onset of type 1 diabetes, 10 of them with diabetic
      ketoacidosis, were subjected to AHSCT with cryopreserved CD34(+) progenitor cells
      and followed up for 31-54 months. MAIN OUTCOME MEASURES: The numbers of different
      subsets of lymphocytes and the levels of serum cytokines, islet antibodies, C
      peptide, and plasma glycosylated hemoglobin were longitudinally measured.
      RESULTS: The numbers of different subsets of lymphocytes, except for CD8(+) T
      cells, in the patients before AHSCT were significantly lower than those in
      controls. However, all lymphocytes gradually recovered after AHSCT, accompanied
      by decreased levels of serum autoantibodies, IL-1, IL-17, and TNF-alpha. After
      AHSCT, 11 of 13 patients required significantly reduced doses of insulin for
      adequate glycemic control, accompanied by reduced levels of glycosylated
      hemoglobin but increased C-peptide concentrations. Three patients achieved
      exogenous insulin independence for 7-54 months. The survival of remaining beta
      cells was associated positively with the preexisting beta-cell function but
      negatively with preexisting autoantibodies (P < 0.05). The numbers of infused
      CD34(+) cells were positively correlated with the concentrations of serum IL-10,
      IL-4, TGF-beta, and fasting C-peptide but negatively correlated with the levels
      of serum TNF-alpha and insulin doses after AHSCT (P < 0.05). CONCLUSION: AHSCT
      modulated lymphocytes and preserved beta-cell function in Chinese patients with
      new onset of type 1 diabetes and diabetic ketoacidosis.

PMID- 22419705
TI  - Complete inhibition of rhTSH-, Graves' disease IgG-, and M22-induced cAMP
      production in differentiated orbital fibroblasts by a low-molecular-weight TSHR
      antagonist.
AB  - The TSH receptor (TSHR) on orbital fibroblasts (OF) is a proposed target of the
      autoimmune attack in Graves' ophthalmopathy. In the present study, we tested
      whether the novel low-molecular-weight (LMW) TSHR antagonist Org-274179-0
      inhibits cAMP production induced by rhTSH, Graves' disease IgG (GD-IgG), or M22
      (a potent human monoclonal TSHR stimulating antibody) in cultured and
      differentiated OF from Graves' ophthalmopathy patients. cAMP production
      significantly increased after incubation either with 10 mU/ml rhTSH (3-fold; P <=
      0.05), 1 mg/ml GD-IgG (2-fold; P <= 0.05), or 500 ng/ml M22 (5-fold; P <= 0.05).
      Incubation with the LMW TSHR antagonist dose dependently inhibited rhTSH, GD-IgG
      as well as the M22-induced cAMP production at nanomolar concentrations; complete
      blockade was affected at 10(-6) M. Our results suggest that GD-IgG- and M22
      induced cAMP production in differentiated OF is exclusively mediated via the TSHR
      because it can be completely blocked by the LMW TSHR antagonist, Org 274179-0.

PMID- 22419706
TI  - Anemia and thrombocytopenia improves after curative parathyroidectomy in a
      patient of primary hyperparathyroidism (PHPT).
AB  - CONTEXT: Hematological manifestations are less known in primary
      hyperparathyroidism (PHPT). Anemia has been recognized as a complication of PHPT
      in 5-30% of the individuals in various series. OBJECTIVE: Our objective was to
      identify hematological improvement after the curative parathyroidectomy in a PHPT
      patient with anemia and thrombocytopenia. PATIENT AND METHODS: A 30-yr-old female
      presented with recurrent renal stone disease, anemia, and thrombocytopenia
      diagnosed as PHPT. Bone marrow examination revealed megakaryocytic
      thrombocytopenia. Two months after the curative parathyroidectomy, her symptoms
      and hematological parameters were improved. CONCLUSION: Our finding showed a
      causal association of both anemia and thrombocytopenia with marrow fibrosis in a
      symptomatic PHPT patient because both anemia and thrombocytopenia improved after
      the curative parathyroidectomy.

PMID- 22419707
TI  - Proangiogenic effect of TSH in human microvascular endothelial cells through its
      membrane receptor.
AB  - CONTEXT: TSH, which acts via specific cell membrane TSH receptors (TSHR), is
      regarded as a thyroid-specific growth factor. Recently, the presence of TSHR has
      been reported in extrathyroid tissues, but the role of TSH in nonthyroid tissue
      is unknown. OBJECTIVE: Our objective was to study the direct effect of TSH on
      angiogenesis in a human dermal microvascular endothelial cell line (HMEC-1).
      Parallel experiments were conducted with human primary cardiac microvascular
      endothelial cells (HMVEC-C). DESIGN: TSHR in HMEC-1 was measured by
      immunofluorescence, Western blot, and RT-PCR and its functional activity by
      variation of intracellular cAMP concentrations. The expression of some angiogenic
      genes and angiogenic signaling pathways was also evaluated after TSH treatment.
      Assays of cell proliferation and capillary network formation on collagen or
      Matrigel were performed in HMEC-1 cells and HMVEC-C. RESULTS: We showed the
      presence of TSHR in HMEC-1 cells. Increased intracellular cAMP concentrations
      after TSH treatment indicated the TSHR to be functional. TSH enhanced
      proliferation and stimulated capillary network formation in HMEC-1, whereas
      antibodies against vascular endothelial growth factor (VEGF) and TSHR abolished
      this effect. TSH increased AAMP, VEGF, and eNOS expression. TSH induced
      phosphorylation of protein kinase S6K1, whereas TSHR blocking antibodies
      inhibited the phosphorylation of the protein kinase S6K1. A similar effect of TSH
      on capillary network formation was observed in HMVEC-C. CONCLUSION: Our findings
      provide strong evidence for a direct effect of TSH on angiogenesis through its
      receptor, via cAMP-mammalian target of rapamycin signaling and indicate that this
      effect is VEGF dependent.

PMID- 22419709
TI  - Maternal body mass index is a predictor of neonatal hypoglycemia in gestational
      diabetes mellitus.
AB  - CONTEXT: In diabetic pregnancy, neonatal hypoglycemia (NH) is usually attributed
      to insufficient regulation of maternal glycemic control. Recent data suggest that
      maternal body mass index (BMI) could have an influence. OBJECTIVE: Our objective
      was to determine whether an association exists between maternal prepregnancy BMI
      category and occurrence of NH among infants born to women with gestational
      diabetes mellitus (GDM). DESIGN AND SETTING: This was a retrospective study
      including all GDM pregnancies delivered between 1986 and 2006 at a tertiary care
      center (Hospital de la Santa Creu i Sant Pau, Barcelona). PATIENTS AND OUTCOMES:
      GDM was diagnosed using universal screening and National Diabetes Data Group
      criteria. Two thousand ninety-two newborns (1925 singletons, 85% of total GDM
      offspring) were studied. NH was defined according to Cornblath criteria. In
      addition to maternal BMI, we considered other variables such as glucose values at
      diagnosis or third-trimester glycated hemoglobin as potential predictors of NH.
      We explored whether the association between maternal BMI and NH could be due to
      intermediate steps such as cesarean section or abnormal birth weight. RESULTS:
      The rate of NH was 3%. In the bivariate analysis, prepregnancy BMI was higher in
      the NH group (24.45 vs. 23.19 kg/m(2), P < 0.02). In the logistic regression
      analysis, prepregnancy BMI of at least 25 kg/m(2) was independently associated
      with NH whether the analysis included intermediate variables (odds ratio = 2.11;
      95% confidence interval = 1.10-4.03) or not (odds ratio = 2.66; 95% confidence
      interval = 1.44-4.92). CONCLUSIONS: Pregestational BMI should be considered among
      the predictors of NH in offspring of women with GDM.

PMID- 22419708
TI  - Body composition and cardiovascular risk markers after remission of Cushing's
      disease: a prospective study using whole-body MRI.
AB  - CONTEXT: Cushing's Disease (CD) alters fat distribution, muscle mass, adipokine
      profile, and cardiovascular risk factors. It is not known whether remission
      entirely reverses these changes. OBJECTIVES: Our objective was to determine
      whether the adverse body composition and cardiovascular risk profile in CD change
      after remission. DESIGN, SETTING, AND PATIENTS: Fourteen CD patients were studied
      prospectively: before surgery (active disease) and again postoperatively 6 months
      after discontinuing oral glucocorticoids (remission). Whole-body magnetic
      resonance imaging was used to examine lean and fat tissue distributions. OUTCOME
      MEASURES: Body composition (skeletal muscle and fat in the visceral, bone marrow,
      sc, and inter-muscular compartments) and cardiovascular risk factors (serum
      insulin, glucose, leptin, high-molecular-weight adiponectin, C-reactive protein,
      and lipid profile) were measured in active CD and remission (mean 20 months after
      surgery). RESULTS: Remission decreased visceral, pelvic bone marrow, sc
      (including trunk and limb sc), and total fat; waist circumference; and weight (P
      < 0.05). Remission altered fat distribution, resulting in decreased
      visceral/total fat (P = 0.04) and visceral fat/skeletal muscle ratios (P =
      0.006). Remission decreased the absolute muscle mass (P = 0.015). Cardiovascular
      risk factors changed: insulin resistance, leptin, and total cholesterol decreased
      (P < 0.05), but adiponectin, C-reactive protein, and other lipid measures did not
      change. CONCLUSIONS: CD remission reduced nearly all fat depots and reverted fat
      to a distribution more consistent with favorable cardiovascular risk but
      decreased skeletal muscle. Remission improved some but not all cardiovascular
      risk markers. Remission from CD dramatically improves body composition
      abnormalities but may still be associated with persistent cardiovascular risk.

PMID- 22419710
TI  - A functional allelic variant of the FGF23 gene is associated with renal phosphate
      leak in calcium nephrolithiasis.
AB  - BACKGROUND: A significant percentage of patients with calcium nephrolithiasis and
      normal parathyroid function have renal phosphate leak. This disorder is
      characterized by idiopathic hypophosphatemia and reduced renal phosphate
      threshold normalized for the glomerular filtration rate (TmPi/GFR). The majority
      of these patients harbor high or inappropriately normal circulating levels of
      fibroblast growth factor 23 (FGF23), a hormone regulating phosphate homeostasis.
      AIM: The aim of this study was to define the role of FGF23 allelic variants in
      the pathogenesis of hypophosphatemic nephrolithiasis. SUBJECTS AND METHODS: We
      sequenced the regulative and coding regions of the FGF23 gene in 106 stone
      formers, 17 of which had renal phosphate leak, and in 87 healthy controls. We
      subsequently performed in vitro studies. RESULTS: A C716T nonsynonymous change
      (T239M, rs7955866) in the FGF23 gene was detected in seven of the 17 stone
      formers with renal phosphate leak. The prevalence of the T allele and of the CT
      genotype in stone formers with renal phosphate leak was significantly higher
      compared to that observed in stone formers without renal phosphate leak and in
      controls (P < 0.03 in all cases). In the whole study population, FGF23(716T)
      subjects showed levels of serum phosphate and TmPi/GFR significantly lower
      compared to FGF23(716C) subjects. In vitro studies showed that the T239M change
      increases FGF23 secretion and that the FGF23(239M) variant induces a higher
      activation of the FGF receptor/ERK pathway compared to FGF23(239T). CONCLUSION:
      Our results highlight a novel significant association between the C716T missense
      variation in the FGF23 gene and calcium nephrolithiasis with renal phosphate
      leak.

PMID- 22419712
TI  - Tuberculum sellae meningioma growing during pregnancy: a difficult decision
      making process.

PMID- 22419711
TI  - Clinical review: Screening for coronary artery disease in type 2 diabetes.
AB  - CLINICAL CONTEXT: Sensitive tools are available to diagnose occult ischemic and
      atherosclerotic coronary disease, yet screening for coronary artery disease (CAD)
      has not been shown to reduce cardiac events in patients with type 2 diabetes
      mellitus (T2DM). Professional guidelines are inconsistent regarding CAD screening
      recommendations, but it is suggested that those at highest risk (10-yr risk
      >=20%) for cardiac events may benefit. EVIDENCE ACQUISITION: We reviewed
      bibliographies of professional CAD screening guidelines, review articles, and
      clinical trials published within the last 10 yr, although we have included
      relevant older studies. We excluded studies that did not focus on T2DM or
      explicitly analyze that subgroup. EVIDENCE SYNTHESIS: Although screening for
      coronary ischemia or atherosclerosis does provide incremental prognostic
      information in patients with T2DM and previously undiagnosed CAD, this has not
      been found to significantly impact outcomes. This appears to result from
      comparable efficacy of revascularization and optimal medical therapy in stable
      CAD. Limited evidence supports the hypothesis that those with more severe CAD
      (three-vessel, left main, proximal left anterior descending) amenable to bypass
      surgery may be potential beneficiaries of screening. However, the low prevalence
      of such candidates in the asymptomatic population, continuing advances with
      percutaneous intervention, and the lack of prospective trials makes such a
      recommendation currently unsupportable. CONCLUSIONS: Findings to date do not
      support widespread screening for CAD in patients with T2DM. A future strategy
      identifying those at highest risk as screening candidates may ultimately be
      effective, but the optimal method for selecting those subjects or subsequent
      treatment is unknown.

PMID- 22419713
TI  - Expression of Ki-67, PTTG1, FGFR4, and SSTR 2, 3, and 5 in nonfunctioning
      pituitary adenomas: a high throughput TMA, immunohistochemical study.
AB  - CONTEXT: Nonfunctioning pituitary adenomas (NFPA) are the most common pituitary
      neoplasms. There is no clinical, biochemical, or histopathological marker that
      would accurately predict recurrence of NFPA. OBJECTIVE: The aim of this study was
      to evaluate a large group of NFPA for the presence of potential markers of
      biological behavior. DESIGN AND SETTING: A cross-sectional study using a high
      throughput tissue microarray technology was conducted at tertiary care centers.
      MATERIALS AND METHODS: Seventy-four gonadotroph and null cell adenomas were
      included in the tissue microarray. Using highly specific antibodies and
      appropriate controls, we determined the expression of Ki-67, pituitary tumor
      transforming gene 1, the N-terminally truncated pituitary tumor-derived
      fibroblast growth factor receptor-4 (FGFR4), as well as somatostatin receptor
      subtypes 2, 3, and 5 (SSTR2, -3, and -5), in an attempt to establish correlations
      and/or associations with clinical characteristics of the patients. RESULTS:
      Median Ki-67 index was 1.49 (interquartile range, 0.62-2.49). Pituitary tumor
      transforming gene 1 nuclear immunoreactivity was found in all but one tumor
      (median percentage of positive nuclei, 11.44); immunopositivity for FGFR4 was
      found in the majority of the tumors, with variable levels of expression. The
      immunostaining score for SSTR2 was significantly higher than that for SSTR3 or
      SSTR5. FGFR4 expression correlated positively with SSTR2 and SSTR5 immunostaining
      scores (r = 0.59; P < 0.001; and r = 0.46; P < 0.001, respectively). Multivariate
      analysis revealed that the Ki-67 index was significantly associated with a tumor
      size greater than 3 cm (odds ratio, 2.32; 95% confidence interval, 1.17-4.58) as
      well as with tumor recurrence (odds ratio, 1.4; 95% confidence interval, 1.03
      1.89). CONCLUSIONS: Ki-67 is the most consistent marker of biological behavior in
      NFPA. The finding of significant amounts of SSTR2 and SSTR5 may have therapeutic
      implications regarding the use of somatostatin analogs in preventing tumor
      recurrence.

PMID- 22419714
TI  - Effect of type 2 diabetes predisposing genetic variants on colorectal cancer
      risk.
AB  - BACKGROUND: The link between colorectal cancer (CRC) and type 2 diabetes mellitus
      (T2D) has been extensively studied. Although it is commonly accepted that T2D is
      a risk factor for CRC, the underlying mechanisms are still poorly understood.
      RESEARCH DESIGN AND METHODS: Given that the genetic background contributes to
      both traits, it is conceivable that genetic variants associated with T2D may also
      influence the risk of CRC. We selected 26 T2D-related single-nucleotide
      polymorphisms (SNP) previously identified by genome-wide association studies and
      assessed their association with CRC and their interaction with known risk factors
      (gender, T2D, and body mass index) of CRC. Selected SNP were genotyped in 1798
      CRC cases and 1810 controls from the population-based Darmkrebs: Chancen der
      Verhutung durch Screening (DACHS) study (Germany). RESULTS: Patients carrying the
      TCF7L2_rs7903146_T allele had an increased risk of CRC (P(trend) = 0.02), whereas
      patients harboring the IL13_rs20541_T allele had a reduced risk (P(trend) =
      0.02). A further analysis revealed gender-specific effects: the
      TCF7L2_rs7903146_T allele was associated with an increased risk of CRC in women
      (P(trend) = 0.003) but not in men (P(interaction) = 0.06); the LTA_rs1041981_A
      allele was associated with a decreased risk for CRC in women (P(trend) = 0.02),
      with an opposite effect in men (P(trend) = 0.05; P(interaction) = 0.002); the
      CDKAL1_rs7754840_C allele was associated with a decreased risk for CRC in men
      (P(trend) = 0.03), with no effect in women (P(interaction) = 0.03). The risk
      associated with the presence of T2D was modified both by IGF2BP2_rs4402960 and
      PPARgamma_rs1801282 SNP (P(interaction) = 0.04 and 0.04, respectively). None of
      the findings were significant after correction for multiple comparisons.
      CONCLUSIONS: These findings suggest that T2D-related variants modify CRC risk
      independently and/or in an interactive manner according to the gender and the
      presence or absence of T2D.

PMID- 22419715
TI  - Hyperinsulinemia amplifies GnRH agonist stimulated ovarian steroid secretion in
      women with polycystic ovary syndrome.
AB  - CONTEXT: In vitro data show that insulin may enhance basal and LH-stimulated
      ovarian androgen secretion, particularly in theca cells from women with
      polycystic ovary syndrome (PCOS). However, in vivo studies gave inconsistent
      results. OBJECTIVE: The objective of the study was to assess whether
      hyperinsulinemia affects in vivo ovarian steroid secretion and steroid
      metabolism. DESIGN AND SETTINGS: This was a controlled cross-sectional study,
      conducted in a tertiary care academic center. PARTICIPANTS: Nine young PCOS women
      participated in the study. INTERVENTION: Participants were submitted, in two
      separate days, to a GnRH agonist stimulation (buserelin 100 MUg, s.c.), during a
      17-h hyperinsulinemic (80 mU/m(2) . min) euglycemic clamp and, as a control,
      during saline infusion. Adrenal steroid secretion was suppressed by
      dexamethasone. MAIN MEASURES: During both protocols, before and after GnRH
      agonist stimulation, serum insulin, gonadotropins, cortisol, progesterone, 17
      hydroxyprogesterone, androstenedione, testosterone, estradiol, and urinary
      androgen metabolites were measured. RESULTS: Insulin increased from 25.1 +/- 13.3
      to 341.5 +/- 102.6 mU/liter during the clamp, whereas it did not significantly
      change during saline infusion. Baseline steroids and gonadotropins were similar
      in the two protocols. During hyperinsulinemia, GnRH agonist-stimulated serum
      progesterone and androstenedione were significantly higher than during saline
      infusion, and 17-hydroxyprogesterone was of borderline significance. Moreover, 24
      h after GnRH agonist stimulation, testosterone was higher after hyperinsulinemia.
      Serum gonadotropins and estradiol response did not differ between the protocols.
      Urinary androgen metabolites excretion significantly increased after GnRH agonist
      stimulation, but the increase was similar during insulin and saline infusions.
      CONCLUSIONS: These in vivo data show that sustained hyperinsulinemia potentiates
      gonadotropin-stimulated ovarian androgen steroidogenesis. Insulin-induced
      increase in ovarian hormone secretion is not accompanied by an increased steroid
      metabolism.

PMID- 22419717
TI  - WITHDRAWN: TNF-Related Apoptosis-Inducing Ligand TRAIL as a Potential Biomarker
      for Early Pregnancy Complications.
AB  - This paper was withdrawn at the request of the editors due to uncertainties
      inherent in the statistical analysis.

PMID- 22419716
TI  - A population-based prospective cohort study of complications after thyroidectomy
      in the elderly.
AB  - CONTEXT: Data on the risk of postthyroidectomy complications in elderly patients
      are sparse, unclear, and conflicting. OBJECTIVE: We sought to use a population
      based cohort to determine whether thyroid operations in the elderly are as safe
      as those done in younger patients. DESIGN: This was a prospective cohort study
      using the American College of Surgeons National Surgical Quality Improvement
      Program database from 2005 to 2008, with 30-d postoperative follow-up. SETTING:
      The American College of Surgeons National Surgical Quality Improvement Program
      data set contains operative cases from a nationwide sampling of academic and
      community-based as well as high-volume and low-volume hospitals. PATIENTS: All
      thyroidectomy and parathyroidectomy patients reported to the database during the
      study period were included in the analysis resulting in an experimental cohort of
      7915 thyroidectomy cases and a control cohort of 3575 parathyroidectomy cases.
      MAIN OUTCOME MEASURES: We aggregated 83 complications into the following outcome
      measures: urinary tract infection, wound infection, systemic infection, cardiac
      complications, pulmonary complications, 30-d mortality, and total hospital length
      of stay. RESULTS: Increased age is a risk factor for significant pulmonary,
      cardiac, and infectious complications after thyroidectomy. Elderly patients are
      twice as likely (odds ratio 2.1, 95% confidence interval 1.4-3.3), and the
      superelderly are 5 times as likely (odds ratio 4.9, 95% confidence interval 2.5
      9.6) to have a complication compared with their young counterparts. Preexisting
      comorbidities are effect modifiers and increase the risk of complications even
      further. CONCLUSIONS: Elderly thyroidectomy patients are at increased risk for
      major systemic complications. A systematic approach to the care of elderly
      thyroidectomy patients is necessary to minimize their risk of serious
      postoperative complications.

PMID- 22419718
TI  - Confirmatory testing in primary aldosteronism.
AB  - CONTEXT: Although confirmatory testing to verify aldosterone excess is a key step
      in the diagnosis of primary aldosteronism (PA), there is no consensus as to
      whether it is always needed and which of the tests need to be performed.
      OBJECTIVE: The objective of this study was to investigate the diagnostic
      significance of confirmatory tests in PA. DESIGN AND PATIENTS: In group A, 120
      hypertensive patients who had positive case detection using the aldosterone to
      renin ratio (ARR) were subjected to at least one confirmatory test: the captopril
      challenge test (CCT), furosemide upright test (FUT), or saline infusion test
      (SIT). Among group A, 57 patients underwent all three confirmatory tests (group
      B), and 57 patients were differentiated as having either unilateral or bilateral
      PA based upon adrenal venous sampling, adrenal scintigraphy, and/or adrenal
      surgery (group C). RESULTS: The percentages of patients with positive CCT and FUT
      were 86 and 87% in group A, 88 and 88% in group B, and 96 and 94% in group C,
      respectively. The percentage of patients with positive SIT results was lower than
      that with other tests (P < 0.01). The percentage of patients with positive
      results for the three tests was higher in patients with baseline ARR of at least
      1000 or plasma aldosterone concentration (PAC) of at least 250 pg/ml than in
      those with lower ARR or PAC in all three groups. CONCLUSIONS: Most patients with
      positive case detection also had positive results on the CCT and FUT, especially
      when ARR was at least 1000 or PAC was at least 250 pg/ml under renin suppresion.
      Confirmatory testing for PA may not be needed in all patients with positive case
      detection.

PMID- 22419719
TI  - Low testosterone levels and increased inflammatory markers in patients with
      cancer and relationship with cachexia.
AB  - CONTEXT: Male cancer patients suffer from fatigue, sexual dysfunction, and
      decreased functional performance and muscle mass. These symptoms are seen in men
      with hypogonadism and/or inflammatory conditions. However, the relative
      contribution of testosterone and inflammation to symptom burden in cancer has not
      been well-established. OBJECTIVE: The aim of this study was to measure
      testosterone levels in male cancer patients and determine the relationship
      between testosterone, inflammation, and symptom burden. DESIGN/SETTING: This
      cross-sectional study enrolled patients from a tertiary-care center.
      SUBJECTS/OUTCOME MEASURES: Subjects included males with cancer-cachexia (CC; n =
      45) and cancer without cachexia (CNC; n = 50), as well as noncancer controls (CO;
      n = 45). Total testosterone (TT), bioavailable testosterone, C-reactive protein
      (CRP), and IL-6 were measured in plasma. Functional performance was assessed by
      the ECOG (Eastern Cooperative Oncology Group) and KPS (Karnofsky Performance
      Scales), and sexual function was assessed by the IIEF (International Index of
      Erectile Function). RESULTS: Low testosterone levels were seen in more than 70%
      of CC cases. TT was lower in CC compared to CNC (P < 0.05). Also, CC had lower
      bioavailable testosterone, grip strength, IIEF scores, appendicular lean body
      mass, and fat mass and higher IL-6 and CRP compared to controls (P <= 0.05). ECOG
      and KPS were lower in CC and CNC compared to controls (P <= 0.05). On multiple
      regression analysis, TT, albumin, and CRP predicted symptoms differentially in
      cancer patients. CONCLUSIONS: CC patients have higher inflammation and lower
      testosterone, grip strength, functional status, erectile function, fat mass, and
      appendicular lean body mass. Inflammation, TT, and albumin are associated with
      heavier symptom burden in this population. Interventional trials are needed to
      determine whether testosterone replacement and/or antiinflammatory agents benefit
      cancer patients.

PMID- 22419721
TI  - Progesterone receptor-A and -B have opposite effects on proinflammatory gene
      expression in human myometrial cells: implications for progesterone actions in
      human pregnancy and parturition.
AB  - CONTEXT: Progesterone promotes uterine relaxation during pregnancy and its
      withdrawal induces labor. Progesterone withdrawal in human parturition is
      mediated in part by changes in the relative levels of the nuclear progesterone
      receptor isoforms, PR-A and PR-B, in myometrial cells. Parturition also involves
      myometrial inflammation; however, the functional link between nuclear PR-mediated
      progesterone actions and inflammation in human myometrial cells is unclear.
      OBJECTIVE: Our objective was to determine how PR-A and PR-B regulate progesterone
      action in human myometrial cells and specifically the expression of genes
      encoding contraction-associated proteins and proinflammatory mediators. DESIGN:
      Effects of PR-A and PR-B on the capacity for progesterone to modulate gene
      expression was determined using an immortalized human myometrial cell line stably
      transfected with inducible PR-A and PR-B expression transgenes and conditioned to
      express various PR-A and PR-B levels. Gene expression was assessed by genome wide
      transcriptome analysis, quantitative RT-PCR and immunoblotting. RESULTS: PR-A and
      PR-B were each transcriptionally active in response to progesterone and affected
      the expression of distinct gene cohorts. The capacity for progesterone to affect
      gene expression was dependent on the PR-A to PR-B ratio. This was especially
      apparent for the expression of proinflammatory genes. Progesterone decreased
      proinflammatory gene expression when the PR-A to PR-B ratio favored PR-B and
      increased proinflammatory gene expression when the ratio favored PR-A.
      Progesterone via PR-B increased expression of inhibitor-kappaBalpha, a repressor
      of the nuclear factor-kappaB transcription factor, and inhibited basal and
      lipopolysaccharide-induced proinflammatory gene expression. Both of those PR-B
      mediated effects were inhibited by PR-A. CONCLUSIONS: Our data suggest that
      during most of human pregnancy, when myometrial cells are PR-B dominant,
      progesterone promotes myometrial quiescence through PR-B-mediated
      antiinflammatory actions. At parturition, the rise in PR-A expression promotes
      labor by inhibiting the antiinflammatory actions of PR-B and stimulating
      proinflammatory gene expression in response to progesterone.

PMID- 22419722
TI  - Melanocortin 2 receptor-associated protein (MRAP) and MRAP2 in human
      adrenocortical tissues: regulation of expression and association with ACTH
      responsiveness.
AB  - CONTEXT: ACTH stimulates adrenocortical steroid production through the
      melanocortin 2 receptor (MC2R). MC2R trafficking and signaling are dependent on
      the MC2R accessory protein (MRAP). The MRAP homolog MRAP2 also transports the
      MC2R to the cell surface but might prevent activation. OBJECTIVE: The objective
      of the investigation was to study the regulatory pathways of MRAP and MRAP2 and
      their contributions to ACTH responsiveness in human adrenal tissues. DESIGN AND
      SETTING: MRAP, MRAP2, and MC2R expression levels were studied in 32 human
      adrenocortical samples. Regulation of these mRNAs was investigated in 43 primary
      adrenal cultures, stimulated with ACTH, forskolin, angiotensin II (AngII),
      phorbol-12-myristate-13-acetate (PMA), or dexamethasone. The induction of
      cortisol, cAMP, and ACTH-responsive genes after treatment with ACTH was related
      to MRAP, MRAP2, and MC2R expression levels. RESULTS: MRAP and MRAP2 levels were
      lower in adrenocortical carcinomas (ACC) than in other adrenal tissues (P <
      0.001). Patient ACTH and cortisol levels were associated with adrenal levels of
      MRAP and MC2R in adrenal hyperplasia samples (P < 0.05) but not in tumors. ACTH
      induced the expression of MRAP 11 +/- 2.1-fold and MC2R 20 +/- 3.8-fold in all
      adrenal tissue types (mean +/- SEM, both P < 0.0001), whereas AngII augmented
      these mRNAs 4.0 +/- 1.2-fold and 12.6 +/- 3.2-fold (P < 0.0001) in all but the
      ACC. MRAP2 expression was suppressed by forskolin (-24 +/- 15%, P = 0.013) and
      PMA (-22 +/- 7%, P = 0.0007). MRAP, MRAP2, or MC2R levels were not associated
      with the induction of cortisol, cAMP, or gene expression by ACTH in vitro.
      CONCLUSION: MRAP and MC2R expression is induced by ACTH and AngII, which would
      facilitate cell surface receptor availability. Physiological expression levels of
      MRAP, MRAP2, and MC2R were not limiting for ACTH sensitivity.

PMID- 22419720
TI  - Characteristics of androgen deficiency in late-onset hypogonadism: results from
      the European Male Aging Study (EMAS).
AB  - CONTEXT: Late-onset hypogonadism (LOH) has been defined as a syndrome in middle
      aged and elderly men reporting symptoms in the presence of low testosterone (T).
      OBJECTIVE: The objective of the study was to seek objective biochemical and end
      organ evidence of androgen deficiency in men classified as having LOH according
      to our previously published criteria. DESIGN, SETTING, AND PARTICIPANTS: The
      design of the study included cross-sectional data from the European Male Aging
      Study on 2966 community-dwelling men aged 40-79 years in eight European
      countries. MAIN OUTCOME MEASURE(S): Waist circumference, body mass index, muscle
      mass, estimated heel bone mineral density (eBMD), hemoglobin, insulin
      sensitivity, physical activity, metabolic syndrome, insulin resistance index, and
      cardiovascular disease were measured. RESULTS: Sixty-three men (2.1%) were
      classified as having LOH: 36 moderate and 27 severe. They were older and more
      obese than eugonadal men and had, in proportion to the graded T deficiency, lower
      muscle mass, eBMD, and hemoglobin, with poorer general health. Both moderate and
      severe LOH was associated with lower hemoglobin, mid-upper arm circumference,
      eBMD, physical function (measured by the Short Form-36 questionnaire), slower
      gait speed and poorer general health. Only men with severe LOH showed significant
      associations with larger waist circumference (beta=1.93 cm; 0.04-3.81), insulin
      resistance (beta=2.81; 1.39-4.23), and the metabolic syndrome (odds ratio 9.94;
      2.73-36.22) after adjustments for confounders. Men with low testosterone only
      (irrespective of symptoms) showed lesser magnitudes of association with the same
      end points. CONCLUSIONS: LOH is associated with multiple end-organ deficits
      compatible with androgen deficiency. These data support the existence of a
      syndrome of LOH in only a minority of aging men, especially those with T below 8
      nmol/liter.

PMID- 22419723
TI  - Link between adipose tissue angiogenesis and fat accumulation in severely obese
      subjects.
AB  - BACKGROUND: White adipose tissue (WAT) can rapidly expand or regress under
      different nutritional conditions. The role of angiogenesis in the expandability
      of human adipose tissue is established. However, whether sc and omental WAT
      (scWAT and oWAT) angiogenesis could influence fat distribution and metabolic
      diseases is not known. AIM: The aim of this study was to analyze whether the
      capacity of angiogenesis in scWAT and oWAT correlates with fat accumulation and
      fat loss, fat distribution, adipocyte hypertrophy, and metabolic disorders in
      obese subjects. METHODS: Samples of scWAT and oWAT were obtained during bariatric
      surgery in 29 obese nondiabetic subjects. Vascular density and inflammatory
      infiltrate were analyzed by immunohistochemistry, and expression of angiogenic
      genes was analyzed by quantitative PCR. These parameters were correlated with
      anthropometric and metabolic parameters. RESULTS: Vascular density of scWAT
      correlated positively with body mass index, whereas vascular density of the oWAT
      correlated with waist circumference. There was no correlation of markers of
      angiogenesis and metabolic disorders. The number of vessels per adipocyte and the
      expression level of receptor 2 of vascular endothelial growth factor correlated
      with adipocyte area in scWAT and oWAT. Finally, weight loss after bariatric
      surgery correlated negatively with adipocyte hypertrophy and vascular density and
      positively with inflammation and angiogenesis of WAT. CONCLUSION: Angiogenesis
      may influence WAT expansion and plasticity but does not appear to be involved in
      the development of insulin resistance in subjects with severe obesity.

PMID- 22419725
TI  - Fecundity in young adults treated early for congenital hypothyroidism is related
      to the initial severity of the disease: a longitudinal population-based cohort
      study.
AB  - CONTEXT: Untreated hypothyroidism is known to impair fecundity. Patients treated
      early for congenital hypothyroidism (CH) have yet to be evaluated in adulthood,
      because screening programs have been running for only the last 30 years in most
      industrialized countries. OBJECTIVE: Our objective was to assess the fecundity of
      young adults treated early for CH and its determinants. DESIGN, SETTING, AND
      PARTICIPANTS: Of the 1748 subjects diagnosed with CH in the first 10 yr after the
      introduction of neonatal screening in France, 1158 completed a questionnaire on
      fecundity at a mean age of 25.3 yr. This self-administered questionnaire focused
      on first attempts to have a child and time to pregnancy. The control group was
      that used in an analogous study on subjects born between 1971 and 1985. MAIN
      OUTCOME MEASURES: Fecundability hazard ratios (HR) were estimated with Cox
      regression models and adjusted for known fecundity confounders (age, smoking, and
      reproductive history). RESULTS: Fecundability was similar for the CH and control
      groups: HR = 1.14 (0.89-1.47) for women, and HR = 0.98 (0.58-1.66) for men. In
      women, the most severe initial forms of the disease, athyreosis, absence of bone
      maturation at the knee epiphyseal ossification centers, and a low serum free T(4)
      concentration at diagnosis (<5 pmol/liter), were associated with lower fecundity:
      HR = 0.68 (0.50-0.98) (P = 0.02); HR = 0.65 (0.45-0.94) (p = 0.02) and HR = 0.70
      (0.50-0.97) (P = 0.03), respectively. However, fecundability was not associated
      with age at the start of treatment, initial levothyroxine dose, or the adequacy
      of hypothyroidism control. CONCLUSION: There is no evidence that fecundity is
      generally lower in young adults treated early than in the general population.
      However, fecundity was lower in women suffering from the most severe form of the
      disease.

PMID- 22419724
TI  - Higher levels of IGF-I and adrenal androgens at age 8 years are associated with
      earlier age at menarche in girls.
AB  - CONTEXT: Earlier age at menarche is associated with rapid infancy weight gain and
      childhood obesity. The role of hormone levels in mediating these associations is
      unclear. OBJECTIVE: The aim of this study was to identify childhood hormone
      levels at age 8 yr that are associated with early menarche, independent of body
      size. DESIGN, SETTINGS, AND SUBJECTS: A total of 329 girls from a prospective
      United Kingdom birth cohort study provided blood samples at mean age 8.1 yr
      (range, 8.0-8.5) for hormone measurements and were followed longitudinally to
      establish age at menarche. MAIN OUTCOME MEASURES: Fasting plasma levels of IGF-I,
      androstenedione, dehydroepiandrosterone sulfate (DHEAS), leptin, insulin, IGF
      binding protein-1, and SHBG were measured. Age at menarche was reported by
      questionnaire and categorized as before 12.0, 12.0-13.0, or later than 13 yr.
      RESULTS: Earlier menarche was associated with greater body weight, height, and
      body mass index at age 8 yr (all P-trend <0.001). Before adjustment for body
      size, earlier menarche was associated with higher levels of IGF-I,
      androstenedione, DHEAS, leptin, and fasting insulin, and with lower levels of IGF
      binding protein-1 and SHBG at age 8 yr (all P < 0.01). After adjustment for body
      mass index and height at age 8 yr, only IGF-I (P = 0.004), androstenedione (P =
      0.01), and DHEAS (P = 0.01) remained associated with earlier menarche.
      CONCLUSIONS: Associations between higher levels of IGF-I and adrenal androgens at
      age 8 yr with earlier menarche, independent of body size, support functional
      roles of these hormones in regulating puberty timing in girls. Higher levels of
      these hormones reported in children who exhibited rapid weight gain during
      infancy may indicate their role in developmental pathways leading to earlier
      sexual maturation.

PMID- 22419726
TI  - GPR98/Gpr98 gene is involved in the regulation of human and mouse bone mineral
      density.
AB  - CONTEXT: Genetic factors are important in the development of osteoporosis.
      OBJECTIVE: The aim of this study was to search for novel genes that regulate bone
      mineral density (BMD). DESIGN: We performed a search for 57,244 single-nucleotide
      polymorphisms (SNP) associated with BMD using SNP arrays and a replication study.
      SETTING AND PATIENTS: Baseline examinations were conducted in Japanese
      postmenopausal women. The mean (sd) age of the subjects was 66.5 (8.4) yr. We
      chose five SNP associated with BMD as those having lower combined P values
      between the first-stage (n = 251) and the second-stage (n = 499) analyses than
      the value determined by Bonferroni's correction. We also analyzed the bone
      related phenotypes in knockout mice of a candidate gene. RESULTS: We focused on
      an SNP of G protein-coupled receptor 98 (GPR98) gene that showed a significant P
      value after the multiple-comparison tests in Japanese postmenopausal women. The
      subjects with one or two risk SNP (GG and AG genotype groups) had an increased
      risk of fractures (AA vs. GG + AG; P = 0.043). Femoral BMD was significantly
      lower in 12-wk-old Gpr98-knockout mice than in wild-type mice. A three-point
      bending test revealed that this morphological phenotype did in fact correlate
      with mechanical fragility in Gpr98-knockout mice. Compared with primary wild-type
      osteoblasts, primary Gpr98-deficient osteoblasts had increased Rankl expression
      and induced activity for osteoclastogenesis and osteoclastic function.
      CONCLUSIONS: Genetic analyses in both human and mouse models uncovered the
      importance of the GPR98 gene in the regulation of bone metabolism.

PMID- 22419727
TI  - Cost impact of molecular testing for indeterminate thyroid nodule fine-needle
      aspiration biopsies.
AB  - INTRODUCTION: Molecular testing of fine-needle aspiration (FNA) results helps
      diagnose thyroid cancer, although the additional cost of this adjunct has not
      been studied. We hypothesized that FNA molecular testing of two indeterminate
      categories (follicular lesion of undetermined significance and follicular/Hurthle
      cell neoplasm) can be cost saving. METHODS: For a hypothetical group of euthyroid
      patients with a 1-cm or larger solitary thyroid nodule, a decision-tree model was
      constructed to compare the estimated costs of initial evaluation according to the
      current American Thyroid Association guidelines, either with molecular testing
      (MT) or without [standard of care (StC)]. Model endpoints were either benign FNA
      results or definitive histological diagnosis. RESULTS: Molecular testing added
      $104 per patient to the overall cost of nodule evaluation (StC $578 vs. MT $682).
      In this distributed cost model, MT was associated with a decrease in the number
      of diagnostic lobectomies (9.7% vs. StC 11.6%), whereas initial total
      thyroidectomy was more frequent (18.2% vs. StC 16.1%). Although MT use added a
      diagnostic cost of $5031 to each additional indicated total thyroidectomy
      ($11,383), the cumulative cost was still less than the comparable cost of
      performing lobectomy ($7684) followed by completion thyroidectomy ($11,954) in
      the StC pathway, when indicated by histological results. In sensitivity analysis,
      savings were demonstrated if molecular testing cost was less than $870.
      CONCLUSIONS: Molecular testing of cytologically indeterminate FNA results is cost
      saving predominantly because of reduction in two-stage thyroidectomy. Appropriate
      use of emerging molecular testing techniques may thus help optimize patient care,
      improve resource use, and avoid unnecessary operation.

PMID- 22419728
TI  - Effects of intravenous zoledronate on bone turnover and bone density persist for
      at least five years in HIV-infected men.
AB  - CONTEXT: In HIV-infected men, the antiresorptive effects of zoledronate persist
      for at least 2 yr after the second annual dose. OBJECTIVE: Our objective was to
      determine the duration of action of zoledronate in men. DESIGN AND SETTING: This
      was 4-yr extension of a 2-yr, double-blind, randomized, placebo-controlled trial
      at an academic research center. PARTICIPANTS: Participants included 43 HIV
      infected men with bone mineral density (BMD) T score below -0.5, 35 of whom
      entered the extension study. INTERVENTION: Intervention was annual administration
      of 4 mg iv zoledronate or placebo at baseline and 1 yr and no intervention
      subsequently. MAIN OUTCOME MEASURES: We evaluated changes in the bone turnover
      markers, serum osteocalcin and serum C-telopeptide (CTx), and changes in BMD at
      the lumbar spine, total hip, and total body. RESULTS: There was no time *
      treatment interaction between 1 and 5 yr after the second zoledronate dose for
      osteocalcin or CTx (P > 0.4) or any BMD site (P > 0.7). Between 1 and 5 yr after
      the second dose, on average, osteocalcin was 41% lower (95% confidence interval =
      19-62%; P < 0.001), CTx 52% lower (33-71%; P < 0.001), lumbar spine BMD 3.7%
      greater (0.3-7.0%; P = 0.03), total hip BMD 2.3% greater (0.3-4.3%; P = 0.02),
      and total body BMD 2.5% greater (0.8-4.1%; P = 0.004) in the zoledronate group
      than the placebo group. Five years after the second dose, the between-groups
      differences were 38% (13-62%) for osteocalcin, 49% (20-77%) for CTx, 3.5% (0.7
      6.7%) for lumbar spine BMD, 3.4% (1.4-5.4%) for total hip BMD, and 1.6% (0.2
      3.1%) for total body BMD. CONCLUSION: The effects of two annual 4-mg doses of
      zoledronate in men persist for at least 5 yr after the second dose. Larger trials
      assessing the antifracture efficacy of less frequent dosing of zoledronate are
      justified.

PMID- 22419729
TI  - Heart valve disease among patients with hyperprolactinemia: a nationwide
      population-based cohort study.
AB  - BACKGROUND: Increased risk of heart valve disease during treatment with certain
      dopamine agonists, such as cabergoline, has been observed in patients with
      Parkinson's disease. The same compound is used to treat hyperprolactinemia, but
      it is unknown whether this also associates with heart valve disease. OBJECTIVES:
      The objective of the study was to assess the incidence of diagnosed heart valve
      disease and cardiac valve surgery among patients with hyperprolactinemia,
      compared with a general population cohort in Denmark. DESIGN: This was a
      nationwide, population-based, cohort study based on a nationwide hospital
      registry. METHODS: We identified 2381 hyperprolactinemia patients with a first
      time diagnosis recorded from 1994 through 2010 in the registry, with no previous
      hospital diagnosis of heart valve disease. Each patient was compared with 10 age-
      and gender-matched comparison cohort members from the general population. The
      association between hyperprolactinemia and heart valve disease was analyzed with
      Cox's proportional hazards regression, controlling for potential confounding
      factors. To assess the risk of cardiac valve surgery and avoid ascertainment
      bias, a subanalysis was made in a cohort of 2,387 hyperprolactinemia patients
      with no previous cardiac valve surgery and 23,870 comparison cohort members.
      RESULTS: Nineteen hyperprolactinemic patients (0.80%) were diagnosed with heart
      valve disease during a total of 17,759.8 yr of follow-up, compared with 75
      persons (0.31%) in the comparison cohort during 179,940.6 yr of follow-up
      [adjusted hazard ratio 2.27 (95% confidence interval 1.35-3.82)]. Seven of the 10
      patients treated with cabergoline and diagnosed with heart valve disease were
      asymptomatic and diagnosed on the basis of an echocardiography performed as a
      safety measure. However, only two patients with hyperprolactinemia (0.08%)
      underwent surgery, compared with 28 persons in the general population cohort
      (0.12%) [adjusted hazard ratio 0.55 (95% confidence interval 0.13-2.42)].
      CONCLUSIONS: Data from the present register-based study do not support that
      hyperprolactinemia or its treatment is associated with an increased risk of
      clinically significant heart valve disease.

PMID- 22419730
TI  - A challenging case of hypocalcemia supporting the concept that 25-hydroxyvitamin
      D status is important for intestinal calcium absorption.
AB  - CONTEXT: Intestinal mucosa seems to be responsive not only to circulating
      calcitriol but also to serum 25-hydroxyvitamin D concentrations. OBJECTIVE: We
      report a complex patient with chronic kidney disease who presented with
      symptomatic hypocalcemia (ionized calcium, 0.77 mmol/liter) despite regular
      calcitriol and calcium supplementation. METHODS: Case history, laboratory
      evaluation, and bone biopsies are discussed. RESULTS: Only vigorous treatment
      with im cholecalciferol led to a significant improvement of serum calcium, a
      decrease in PTH levels, and histological improvement of osteomalacic bone
      disease. However, oral anticoagulation became necessary for advanced peripheral
      artery disease, which precluded further im injections. Therefore, UVB
      phototherapy was initiated to treat vitamin D deficiency. CONCLUSION: This case
      is clinically relevant because it demonstrates that efficient calcium absorption
      is markedly reduced in profound vitamin D deficiency, even with normal active
      vitamin D levels. An important consequence is to stay aware of vitamin D
      deficiency in patients with compromised kidney function irrespective of regular
      calcitriol replacement. Second, when both parenteral and oral vitamin D
      administration are contraindicated, ineffective, or unavailable, UVB phototherapy
      is an effective option to treat vitamin D deficiency. Third, this case underlines
      the importance of obtaining regular 25-hydroxyvitamin D levels in complex
      clinical cases when prediction of individual response is unreliable.

PMID- 22419731
TI  - Maternal and fetal IGF-I and IGF-II levels, fetal growth, and gestational
      diabetes.
AB  - CONTEXT: It remains uncertain whether maternal IGF-I is associated with fetal
      growth. Little is known about the role of maternal IGF-II in fetal growth and
      whether IGF-I or IGF-II is implicated in fetal hypertrophy in gestational
      diabetes. OBJECTIVE: The objective of the study was to assess maternal and fetal
      IGF-I and IGF-II levels in association with fetal growth and gestational
      diabetes. STUDY DESIGN, POPULATION, AND OUTCOMES: A singleton pregnancy cohort
      study (n = 307). The primary outcome was birth weight. RESULTS: Maternal plasma
      concentrations increased by an average of 55.4% for IGF-I and 11.8% for IGF-II
      between 24-28 and 32-35 weeks of gestation. The maternal IGF-I but not IGF-II
      level was correlated with birth weight and placental weight. Adjusting for
      maternal and infant characteristics, each SD increase in maternal IGF-I level at
      24-28 weeks was associated with a 75-g (95% confidence intervals 29-120) increase
      in birth weight, a 20-g (7-33) increase in placental weight, and a 1.91-fold
      (1.28-2.86) higher odds of macrosomia (birth weight > 90th percentile). Similar
      associations were observed for the maternal IGF-I level at 32-35 weeks. Maternal
      and fetal IGF-I (but not IGF-II) levels were significantly higher in gestational
      diabetic than in nondiabetic pregnancies. The significantly higher birth weight z
      scores in diabetic pregnancies disappeared after adjusting for maternal and fetal
      IGF-I levels alone. CONCLUSIONS: Higher maternal IGF-I (but not IGF-II) levels at
      mid- and late gestation may indicate greater placental and fetal growth. IGF-I
      (but not IGF-II) may be implicated in fetal hypertrophy in gestational diabetes.

PMID- 22419732
TI  - Efficacy and tolerability of the DPP-4 inhibitor alogliptin combined with
      pioglitazone, in metformin-treated patients with type 2 diabetes.
AB  - CONTEXT: Optimal management of type 2 diabetes remains an elusive goal.
      Combination therapy addressing the core defects of impaired insulin secretion and
      insulin resistance shows promise in maintaining glycemic control. OBJECTIVE: The
      aim of the study was to assess the efficacy and tolerability of alogliptin
      combined with pioglitazone in metformin-treated type 2 diabetic patients. DESIGN,
      SETTING, AND PATIENTS: We conducted a multicenter, randomized, double-blind,
      placebo-controlled, parallel-arm study in patients with type 2 diabetes.
      INTERVENTIONS: The study consisted of 26-wk treatment with alogliptin (12.5 or 25
      mg qd) alone or combined with pioglitazone (15, 30, or 45 mg qd) in 1554 patients
      on stable-dose metformin monotherapy (>=1500 mg) with inadequate glycemic
      control. MAIN OUTCOME MEASURE: The primary endpoint was change in glycosylated
      hemoglobin (HbA(1c)) from baseline to wk 26. Secondary endpoints included changes
      in fasting plasma glucose and beta-cell function. Primary analyses compared
      pioglitazone therapy [all doses pooled, pioglitazone alone (Pio alone); n = 387]
      with alogliptin 12.5 mg plus any dose of pioglitazone (A12.5+P; n = 390) or
      alogliptin 25 mg plus any dose of pioglitazone (A25+P; n = 390). RESULTS: When
      added to metformin, the least squares mean change (LSMDelta) from baseline
      HbA(1c) was -0.9 +/- 0.05% in the Pio-alone group and -1.4 +/- 0.05% in both the
      A12.5+P and A25+P groups (P < 0.001 for both comparisons). A12.5+P and A25+P
      produced greater reductions in fasting plasma glucose (LSMDelta = -2.5 +/- 0.1
      mmol/liter for both) than Pio alone (LSMDelta = -1.6 +/- 0.1 mmol/liter; P <
      0.001). A12.5+P and A25+P significantly improved measures of beta-cell function
      (proinsulin:insulin and homeostasis model assessment of beta-cell function)
      compared to Pio alone, but had no effect on homeostasis model assessment of
      insulin resistance. The LSMDelta body weight was 1.8 +/- 0.2, 1.9 +/- 0.2, and
      1.5 +/- 0.2 kg in A12.5+P, A25+P, and Pio-alone groups, respectively.
      Hypoglycemia was reported by 1.0, 1.5, and 2.1% of patients in the A12.5+P,
      A25+P, and Pio-alone groups, respectively. CONCLUSIONS: In type 2 diabetic
      patients inadequately controlled by metformin, the reduction in HbA(1c) by
      alogliptin and pioglitazone was additive. The decreases in HbA(1c) with A12.5+P
      and A25+P were similar. All treatments were well tolerated.

PMID- 22419733
TI  - Insulin up-regulates natriuretic peptide clearance receptor expression in the
      subcutaneous fat depot in obese subjects: a missing link between CVD risk and
      obesity?
AB  - CONTEXT: Natriuretic peptides (NP) regulate cardiovascular homeostasis and have
      multiple metabolic properties. Decreased levels of NP or "natriuretic handicap"
      are signs of insulin resistance such as central obesity. Increased expression of
      NP clearance receptor (NPRC) in sc adipose tissue (SAT) was observed in insulin
      resistant subjects. OBJECTIVE: We hypothesized that insulin acutely regulates NP
      receptor expression in adipose tissue. DESIGN AND PARTICIPANTS: NPRA, NPRB, and
      NPRC mRNA expression was measured in paired samples of visceral adipose tissue
      (VAT) and SAT from 157 subjects (108 with type 2 diabetes). The effect of insulin
      on NPR gene expression in SAT was studied in euglycemic-hyperinsulinemic and
      hyperglycemic-hyperinsulinemic clamp experiments. Additionally, the effect of
      insulin and glucose on NPR expression in the culture of primary human monocytes
      and macrophages was tested. RESULTS: NPRA and NPRC gene expression was higher in
      VAT compared with SAT (P < 0.01), but only NPRC gene expression strongly
      correlated with fasting insulin levels (r = 0.65, P = 0.04 * 10(-3); and r =
      0.54, P = 0.002, for VAT and SAT, respectively). NPRB expression was lower in VAT
      than in SAT in subjects with type 2 diabetes and was lower compared with
      nondiabetic subjects. NPRC gene expression was up-regulated in SAT during both
      euglycemic- and hyperglycemic-hyperinsulinemic clamps (P = 0.038 and P = 0.048,
      respectively), and was increased in high glucose and insulin treatment in
      monocytes (70.2%; P = 0.01), but not in mature macrophages. CONCLUSION: Insulin
      increased expression of NPRC in SAT independently of circulating glucose
      concentrations. Thus, insulin might suppress circulating NP via up-regulation of
      NPRC expression in obesity, providing a novel link between hyperinsulinemia and
      obesity.

PMID- 22419734
TI  - Genetic polymorphism CYP17 rs2486758 and metabolic risk factors predict daily
      salivary 17beta-estradiol concentration in healthy premenopausal Norwegian women.
      The EBBA-I study.
AB  - CONTEXT: The relationship between low-penetrance genes, metabolic risk factors,
      and levels of endogenous 17beta-estradiol and progesterone, which play a role in
      breast cancer risk, remains unclear. OBJECTIVE: The aim of this study was to
      determine whether common polymorphisms in CYP17, in combination with metabolic
      risk factors (individually or clustered), alter salivary concentrations of free
      biologically active 17beta-estradiol and progesterone among healthy premenopausal
      Norwegian women. DESIGN: Eight single nucleotide polymorphisms in CYP17 were
      genotyped in 203 healthy premenopausal women aged 25-35 yr in the Norwegian EBBA
      I Study, conducted in 2000-2002. Daily salivary concentrations of 17beta
      estradiol and progesterone were measured throughout one menstrual cycle. A
      clustered metabolic score was calculated, including waist circumference, mean
      arterial pressure, insulin resistance, fasting triglycerides, and total
      cholesterol/high-density lipoprotein cholesterol ratio. The study hypothesis was
      tested in multivariable linear regression and generalized estimating equation
      models. RESULTS: Women in the upper tertile of clustered metabolic score with the
      CYP17 rs2486758 minor allele had daily salivary 17beta-estradiol concentrations
      that were 53% higher than other study women throughout the menstrual cycle (P <
      0.001). Similarly, women in the upper tertile of total cholesterol/high-density
      lipoprotein cholesterol ratio, fasting triglycerides, and insulin resistance had
      44, 32, and 24% higher daily salivary 17beta-estradiol concentrations,
      respectively (all P < 0.05). CONCLUSION: The CYP17 rs2486758 minor allele may
      predispose to higher 17beta-estradiol levels, particularly in premenopausal women
      with a high clustered metabolic score. Thus, modification of metabolic risk
      factors may have significant implications for the prevention of breast cancer in
      women with the minor allele of CYP17 rs2486758.

PMID- 22419735
TI  - A novel missense mutation in the SH2 domain of the STAT5B gene results in a
      transcriptionally inactive STAT5b associated with severe IGF-I deficiency, immune
      dysfunction, and lack of pulmonary disease.
AB  - CONTEXT: Signal transducer and activator of transcription 5b (STAT5b) deficiency,
      first reported in a patient who carried a p.Ala630Pro missense mutation in the
      Src homology 2 (SH2) domain, results in a rare clinical condition of GH
      insensitivity (GHI), IGF-I deficiency (IGFD), and severe immune dysregulation
      manifesting as progressive worsening of pulmonary function. PATIENT: The new
      patient presented with severe cutaneous eczema, episodic infections in the first
      years of life, and autoimmune thyroiditis. Immunological evaluation revealed T
      lymphopenia, but severe pulmonary symptoms were notably absent. She concomitantly
      exhibited pronounced growth failure, reaching an adult height of 124.7 cm [-5.90
      SD score (SDS)]. Endocrine evaluations (normal provocative GH tests; low serum
      IGF-I, -3.7 SDS, and IGF-binding protein-3, -4.5 SDS) were consistent with GHI
      and IGFD. RESULTS: Analysis of the STAT5B gene revealed a novel homozygous
      missense mutation, p.Phe646Ser, located within the betaD' strand of the SH2
      domain. Reconstitution studies demonstrated expression of the p.Phe646Ser variant
      was less robust than wild type but, in contrast to the previously described
      STAT5B p.Ala630Pro SH2 mutation, could be phosphorylated in response to GH and
      interferon-gamma. The phosphorylated p.Phe646Ser, however, could not drive
      transcription. CONCLUSION: A novel STAT5B p.Phe646Ser mutation has been
      identified in a patient with clinical characteristics of STAT5b deficiency. Only
      the second STAT5B missense mutation identified, its lack of transcriptional
      activities despite GH-induced phosphorylation, confirms the crucial role of
      STAT5b for regulating the expression of IGF1 and provides insights into the
      importance of the SH2 betaD' strand for full STAT5b transcriptional activities.
      Whether the phosphorylated p.Phe646Ser variant retained functions that prevented
      pulmonary distress remains unresolved.

PMID- 22419736
TI  - Neuropathogenic role of adenylate kinase-1 in Abeta-mediated tau phosphorylation
      via AMPK and GSK3beta.
AB  - Abnormally hyperphosphorylated tau is often caused by tau kinases, such as
      GSK3beta and Cdk5. Such occurrence leads to neurofibrillary tangle formation and
      neuronal degeneration in tauopathy, including Alzheimer's disease (AD). However,
      little is known about the signaling cascade underlying the pathologic
      phosphorylation of tau by Abeta(42). In this study, we show that adenylate kinase
      1 (AK1) is a novel regulator of abnormal tau phosphorylation. AK1 expression is
      markedly increased in the brains of AD patients and AD model mice and is
      significantly induced by Abeta(42) in the primary neurons. Ectopic expression of
      AK1 alone augments the pathologic phosphorylation of tau at PHF1, CP13 and AT180
      epitopes and enhances the formation of tau aggregates. Inversely, downregulation
      of AK1 alleviates Abeta(42)-induced hyperphosphorylation of tau. AK1 plays a role
      in Abeta(42)-induced impairment of AMPK activity and GSK3beta activation in the
      primary neurons. Pharmacologic studies show that treatment with an AMPK inhibitor
      activates GSK3beta, and a GSK3beta inhibitor attenuates AK1-mediated tau
      phosphorylation. In a Drosophila model of human tauopathy, the retinal expression
      of human AK1 severely exacerbates rough eye phenotype and increases abnormal tau
      phosphorylation. Further, neural expression of AK1 reduces the lifespan of tau
      transgenic files. Taken together, these observations indicate that the neuronal
      expression of AK1 is induced by Abeta(42) to increase abnormal tau
      phosphorylation via AMPK-GSK3beta and contributes to tau-mediated
      neurodegeneration, providing a new upstream modulator of GSK3beta in the
      pathologic phosphorylation of tau.

PMID- 22419738
TI  - A genome-wide association study in the Japanese population confirms 9p21 and
      14q23 as susceptibility loci for primary open angle glaucoma.
AB  - Primary open angle glaucoma (POAG) is one of leading causes of adult blindness
      worldwide. To identify genetic variants associated with susceptibility to POAG,
      we conducted a genome-wide association study (GWAS) using 1394 cases and 6599
      controls. Subsequently, we analyzed 33 single nucleotide polymorphisms (SNPs)
      which showed suggestive association (P < 1 * 10(-4)) by GWAS, using an additional
      set of 1802 cases and 7212 controls. In addition to confirmation of the
      association of the chromosome 9p21 locus [rs1063192, P= 5.2 * 10(-11), odds ratio
      (OR) = 0.75], and 14q23 (rs10483727, P = 9.49 * 10(-8), OR = 0.79) with POAG in
      Caucasians reported recently, we identified a suggestive-associated locus on 2q21
      (rs7588567, P = 3.89 * 10(-7), OR = 0.85). For these described SNPs, minor
      alleles are suspected to have a protective effect from the disease. An linkage
      disequilibrium block containing rs10483727 includes the SIX6 gene that was
      implicated to have a critical role in eye development, and genes in both
      represented loci (SIX6 on chromosome 14q23, and CDKN2A-CDKN2B on chromosome 9p21)
      are known to be expressed in human ocular tissues, including the retina. Our GWAS
      results should contribute to better insight into the genetic basis of POAG.

PMID- 22419737
TI  - Response to DNA damage of CHEK2 missense mutations in familial breast cancer.
AB  - Comprehensive sequencing of tumor suppressor genes to evaluate inherited
      predisposition to cancer yields many individually rare missense alleles of
      unknown functional and clinical consequence. To address this problem for CHEK2
      missense alleles, we developed a yeast-based assay to assess in vivo CHEK2
      mediated response to DNA damage. Of 25 germline CHEK2 missense alleles detected
      in familial breast cancer patients, 12 alleles had complete loss of DNA damage
      response, 8 had partial loss and 5 exhibited a DNA damage response equivalent to
      that mediated by wild-type CHEK2. Variants exhibiting reduced response to DNA
      damage were found in all domains of the CHEK2 protein. Assay results were in
      agreement with epidemiologic assessments of breast cancer risk for those variants
      sufficiently common for case-control studies to have been undertaken. Assay
      results were largely concordant with consensus predictions of in silico tools,
      particularly for damaging alleles in the kinase domain. However, of the 25
      variants, 6 were not consistently classifiable by in silico tools. An in vivo
      assay of cellular response to DNA damage by mutant CHEK2 alleles may complement
      and extend epidemiologic and genetic assessment of their clinical consequences.

PMID- 22419739
TI  - MCORES: a system for noun phrase coreference resolution for clinical records.
AB  - OBJECTIVE: Narratives of electronic medical records contain information that can
      be useful for clinical practice and multi-purpose research. This information
      needs to be put into a structured form before it can be used by automated
      systems. Coreference resolution is a step in the transformation of narratives
      into a structured form. METHODS: This study presents a medical coreference
      resolution system (MCORES) for noun phrases in four frequently used clinical
      semantic categories: persons, problems, treatments, and tests. MCORES treats
      coreference resolution as a binary classification task. Given a pair of concepts
      from a semantic category, it determines coreferent pairs and clusters them into
      chains. MCORES uses an enhanced set of lexical, syntactic, and semantic features.
      Some MCORES features measure the distance between various representations of the
      concepts in a pair and can be asymmetric. RESULTS AND CONCLUSION: MCORES was
      compared with an in-house baseline that uses only single-perspective 'token
      overlap' and 'number agreement' features. MCORES was shown to outperform the
      baseline; its enhanced features contribute significantly to performance. In
      addition to the baseline, MCORES was compared against two available third-party,
      open-domain systems, RECONCILE(ACL09) and the Beautiful Anaphora Resolution
      Toolkit (BART). MCORES was shown to outperform both of these systems on clinical
      records.

PMID- 22419740
TI  - Prospective study of human papillomavirus seropositivity and risk of nonmelanoma
      skin cancer.
AB  - Cutaneous human papillomaviruses (HPVs) have been associated with squamous cell
      carcinoma (SCC) in case-control studies, but there are limited data from
      prospective studies assessing whether virus exposure predicts risk of future
      cancer development. Two major biobanks, the Southern Sweden Microbiology Biobank
      (1971-2003) and the Janus Biobank (1973-2003) in Norway, containing samples from
      850,000 donors, were searched for incident skin cancer for up to 30 years using
      registry linkages. Altogether, 2,623 donors with samples taken before diagnosis
      of SCC or basal cell carcinoma (BCC) of the skin were identified. Prediagnostic
      samples and samples from 2,623 matched controls were tested for antibodies
      against 33 types of HPV. Baseline seropositivity to HPV types in genus beta
      species 2 was associated with SCC risk (odds ratio = 1.3, 95% confidence
      interval: 1.1, 1.7); this was also the case for samples taken more than 18 years
      before diagnosis (odds ratio = 1.8, 95% confidence interval: 1.1, 2.8). Type
      specific persistent seropositivity entailed elevated point estimates for SCC risk
      for 29 HPV types and decreased point estimates for only 3 types. After multiple
      hypothesis adjustment, HPV 76 was significantly associated with SCC risk and HPV
      9 with BCC risk. In summary, seropositivity for certain HPV types was associated
      with an increased risk for future development of SCC and BCC.

PMID- 22419741
TI  - Fluctuation of oxidative stress indicators in Salix nigra seeds during priming.
AB  - Salix nigra seeds subjected to increased humidification show a decrease in normal
      germination (NG) during early imbibition followed by a recovery in that parameter
      at increasing imbibition times. Since photo-oxidized seeds contain high levels of
      reactive oxygen species (ROS), it is possible to infer that the atypical decrease
      in NG is a consequence of a higher ROS mobilization at early imbibition and the
      subsequent recovery from an increase in antioxidant activity. In this study,
      several oxidative stress indicators were evaluated in photo-oxidized seeds
      subjected to priming. ROS production was studied using electronic spin resonance
      spectroscopy, spontaneous chemiluminescence (SCL), spectrophotometry (with XTT),
      and histochemical (with DAB and NBT) and cytochemical (with CeCl(3)) techniques.
      Four indicators of molecular damage were monitored: lipid peroxidation, pigment
      destruction, protein oxidation, and membrane integrity. Antioxidant activity was
      evaluated by changes in the enzymes SOD, CAT, APX, and POX. The results revealed
      that the decrease in NG at the beginning of priming occurs by an oxidative burst,
      as determined by increases in both SCL and superoxide anion radical (O2(.-)) Such
      oxidative burst generates lipid peroxidation, protein oxidation, and a decrease
      in both pigment content and enzyme activities. With increasing hydration, damages
      are progressively reversed and NG restored, which coincides with the increased
      activity of antioxidant defences. It is proposed that these novel observations
      regarding the occurrence of an oxidative burst are related to the high basal ROS
      levels and the high membrane content retained in the mature embryo tissues.

PMID- 22419742
TI  - Kinetic modelling of plant metabolic pathways.
AB  - This paper provides a review of kinetic modelling of plant metabolic pathways as
      a tool for analysing their control and regulation. An overview of different
      modelling strategies is presented, starting with those approaches that only
      require a knowledge of the network stoichiometry; these are referred to as
      structural. Flux-balance analysis, metabolic flux analysis using isotope
      labelling, and elementary mode analysis are briefly mentioned as three
      representative examples. The main focus of this paper, however, is a discussion
      of kinetic modelling, which requires, in addition to the stoichiometry, a
      knowledge of the kinetic properties of the constituent pathway enzymes. The
      different types of kinetic modelling analysis, namely time-course simulation,
      steady-state analysis, and metabolic control analysis, are explained in some
      detail. An overview is presented of strategies for obtaining model parameters, as
      well as software tools available for simulation of such models. The kinetic
      modelling approach is exemplified with discussion of three models from the
      general plant physiology literature. With the aid of kinetic modelling it is
      possible to perform a control analysis of a plant metabolic system, to identify
      potential targets for biotechnological manipulation, as well as to ascertain the
      regulatory importance of different enzymes (including isoforms of the same
      enzyme) in a pathway. Finally, a framework is presented for extending metabolic
      models to the whole-plant scale by linking biochemical reactions with diffusion
      and advective flow through the phloem. Future challenges include explicit
      modelling of subcellular compartments, as well as the integration of kinetic
      models on the different levels of the cellular and organizational hierarchy.

PMID- 22419743
TI  - Mutation of Arabidopsis HY1 causes UV-C hypersensitivity by impairing carotenoid
      and flavonoid biosynthesis and the down-regulation of antioxidant defence.
AB  - Previous pharmacological results confirmed that haem oxygenase-1 (HO-1) is
      involved in protection of cells against ultraviolet (UV)-induced oxidative damage
      in soybean [Glycine max (L.) Merr.] seedlings, but there remains a lack of
      genetic evidence. In this study, the link between Arabidopsis thaliana HO-1 (HY1)
      and UV-C tolerance was investigated at the genetic and molecular levels. The
      maximum inducible expression of HY1 in wild-type Arabidopsis was observed
      following UV-C irradiation. UV-C sensitivity was not observed in ho2, ho3, and
      ho4 single and double mutants. However, the HY1 mutant exhibited UV-C
      hypersensitivity, consistent with the observed decreases in chlorophyll content,
      and carotenoid and flavonoid metabolism, as well as the down-regulation of
      antioxidant defences, thereby resulting in severe oxidative damage. The addition
      of the carbon monoxide donor carbon monoxide-releasing molecule-2 (CORM-2), in
      particular, and bilirubin (BR), two catalytic by-products of HY1, partially
      rescued the UV-C hypersensitivity, and other responses appeared in the hy1
      mutant. Transcription factors involved in the synthesis of flavonoid or UV
      responses were induced by UV-C, but reduced in the hy1 mutant. Overall, the
      findings showed that mutation of HY1 triggered UV-C hypersensitivity, by
      impairing carotenoid and flavonoid synthesis and antioxidant defences.

PMID- 22419744
TI  - Time-lapse monitoring as a tool for clinical embryo assessment.
AB  - As elective transfer of a single embryo (eSET) becomes increasingly accepted, the
      need to improve implantation rates becomes crucial. Selecting the most competent
      embryo therefore constitutes a major challenge in assisted reproductive
      technology. Embryo morphology and developmental stage at given time points are
      closely correlated with developmental competence and assessment of morphological
      parameters at discrete inspection points thus remains the preferred way of
      evaluating embryonic potential. Lately, more attention has been given to the
      assessment of dynamic embryo development as a tool for evaluating embryonic
      potential. The introduction of time-lapse equipment approved for use on human
      embryos offers novel clinical opportunities for continuous monitoring of embryos,
      enabling flexible evaluation of known morphological parameters and potentially
      introducing new dynamic markers of viability. Due to lack of larger, randomized
      clinical studies it remains to be elucidated whether embryo selection using
      dynamic parameters improves clinical outcome and which parameters are of
      significance. Before such randomized controlled studies are organized, the most
      promising parameters to evaluate must be identified. This mini-review summarizes
      the current knowledge about dynamic markers of viability and discusses the
      potential clinical role of time-lapse analysis in embryo assessment and
      selection.

PMID- 22419745
TI  - Favorable infertility outcomes following anti-tubercular treatment prescribed on
      the sole basis of a positive polymerase chain reaction test for endometrial
      tuberculosis.
AB  - BACKGROUND: The endometrial tuberculosis (TB) PCR test is now commonly employed
      for the diagnosis of female genital TB, a common cause of infertility in India.
      Although treatment in the absence of demonstrable tubal damage may be of doubtful
      benefit to fertility, the presence of mycobacterial DNA demonstrated by a
      positive PCR indicates infection by tubercle bacilli causing sub-clinical or
      latent disease potentially responsible for future clinical manifestations. This
      study was undertaken to assess the outcome of infertility management following
      early anti-tubercular treatment (ATT) based only on a positive endometrial TB-PCR
      test. METHODS: This was an intervention study conducted at an IVF center in
      northern India in 443 infertile women of whom 169 (38.15%) were found to have
      positive TB-PCR (Group I), while 274 (61.85%) had negative Mycobacterium
      tuberculosis (MTB)-PCR (Group II). Infertile women of <40 years of age, without
      any evidence of tubo-peritoneal or endometrial involvement, who underwent
      endometrial biopsy for the detection of MTB by PCR, were included. All the TB-PCR
      positive women were administered standard 6-month anti-tubercular chemotherapy.
      Additional treatment with assisted reproduction techniques was offered in the
      case of failure of spontaneous pregnancy after completion of ATT. RESULTS: There
      were no statistical differences in the two groups in the overall pregnancy rate,
      101 (59.8%) versus 167 (60.9%). In Group I, 48 (92.3%) spontaneous conceptions
      occurred within the first 12 months, i.e. during the period of ATT administration
      or within 6 months of treatment completion; in Group II, the occurrence of
      spontaneous conceptions was distributed more evenly in relation to time, i.e. 36
      (53.7%) in <12 months as compared with 31 (46.3%) after first year (P< 0.001).
      CONCLUSION: Infertile women without tubal or endometrial damage given early anti
      tuberculosis treatment based on a positive endometrial TB-PCR test had an
      excellent chance of early spontaneous conception.

PMID- 22419746
TI  - Circulating luteinizing hormone level after triggering oocyte maturation with
      GnRH agonist may predict oocyte yield in flexible GnRH antagonist protocol.
AB  - BACKGROUND: The use of gonadotrophin-releasing hormone (GnRH) agonist for
      triggering final oocyte maturation and ovulation can reduce ovarian
      hyperstimulation syndrome (OHSS) in high-risk patients. LH levels post-trigger
      with GnRH agonist might be correlated with oocyte yield and maturity. Our aim was
      to evaluate the relationship between serum LH level at 12-h post-trigger and
      oocyte yield, maturity and fertilization rate in patients at high risk of OHSS
      and therefore who were treated with a flexible GnRH antagonist protocol in which
      final oocyte maturation was triggered with GnRH agonist. METHODS: In a
      prospective cohort study, 91 patients at high risk of OHSS were treated with a
      flexible GnRH antagonist protocol and divided into six groups according to their
      serum LH levels at 12-h after GnRH agonist administration: <=15.0, 15.1-30.0,
      30.1-45.0, 45.1-60.0, 60.1-75.0 and >75.0 IU/l. The oocyte yield, maturity,
      fertilization rate and clinical outcomes for each LH interval were analyzed.
      RESULTS: There was a statistically significant reduction in oocyte yield with a
      concentration of serum LH <=15.0 IU/l (P < 0.05), whereas no statistically
      significant differences in the oocyte maturity and fertilization rate among the
      six groups (P > 0.05) were seen. Only 5 out of 91 patients (5.5%) had a serum LH
      <=15.0 IU/l at 12-h post-trigger with GnRH agonist. In addition, no statistically
      significant difference was seen regarding high-quality embryos, implantation
      rate, clinical pregnancy rate and early miscarriage between patients with LH
      <=15.0 IU/l and >15.0 IU/l (P > 0.05). CONCLUSIONS: Serum LH level at 12-h post
      trigger with GnRHa <15.0 IU/l is associated with a dramatically lower oocyte
      yield but not with the oocyte maturity and fertilization rate. Serum LH levels
      post-trigger with GnRH agonist do not affect clinical outcomes.

PMID- 22419747
TI  - Pitfalls in diagnostic gastrin measurements.
AB  - BACKGROUND: Gastrin measurements are performed primarily for the diagnosis of
      gastrin-producing tumors, gastrinomas, which cause the Zollinger-Ellison syndrome
      (ZES). Gastrin circulates as several bioactive peptides, however, and the peptide
      pattern in gastrinoma patients often deviates from normal. Therefore, it is
      necessary to measure all forms of gastrin. CONTENT: Only immunoassays are useful
      for measurement of gastrin in plasma. The original assays were RIAs developed in
      research laboratories that used antibodies directed against the C terminus of
      gastrin peptides. Because the C-terminal tetrapeptide amide sequence constitutes
      the active site of gastrin peptides, these assays were well suited for gastrinoma
      diagnosis. More recently, however, most clinical chemistry laboratories have
      switched to commercial kits. Because of recent cases of kit-measured
      normogastrinemia in patients with ZES symptoms, the diagnostic sensitivity and
      analytical specificity of the available kits have been examined. The results show
      that gastrin kits frequently measure falsely low concentrations because they
      measure only a single gastrin form. Falsely high concentrations were also
      encountered, owing to overreactivity with O-sulfated gastrins or plasma proteins.
      Thus, more than half of the gastrin kits on the market are unsuited for
      diagnostics. SUMMARY: Gastrinomas are neuroendocrine tumors, some of which become
      malignant. A delay in diagnosis leads to fulminant ZES, with major, even lethal,
      complications. Consequently, it is necessary that the diagnostic sensitivity of
      gastrin kits be adequate. This diagnostic sensitivity requires antibodies that
      bind the C-terminal epitope of bioactive gastrins without the influence of O
      sulfation.

PMID- 22419748
TI  - Plasma kisspeptin: a potential biomarker of tumor metastasis in patients with
      ovarian carcinoma.

PMID- 22419749
TI  - Lipoprotein-associated phospholipase A2 measurements: mass, activity, but little
      productivity.

PMID- 22419750
TI  - Relationship of lipoprotein-associated phospholipase A2 mass and activity with
      incident vascular events among primary prevention patients allocated to placebo
      or to statin therapy: an analysis from the JUPITER trial.
AB  - BACKGROUND: Although lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels
      are associated with cardiovascular events, Lp-PLA(2) is physically linked to LDL
      cholesterol (LDL-C). Whether measures of Lp-PLA(2) mass or activity continue to
      predict risk after LDL-C reduction by statin therapy is uncertain. METHODS: Lp
      PLA(2) mass concentration and activity were evaluated at baseline and after
      treatment in the Justification for the Use of Statins in Prevention: an
      Intervention Trial Evaluating Rosuvastatin (JUPITER) trial comparing rosuvastatin
      20 mg to placebo among 17 802 men and women without cardiovascular disease or
      diabetes at study entry. The relationships of Lp-PLA(2) mass and activity with
      risk of future vascular events were evaluated in the placebo and rosuvastatin
      groups. RESULTS: Before randomization, levels of Lp-PLA(2) mass and activity
      correlated moderately with each other and with LDL-C. The magnitude of these
      correlations increased after statin therapy. Rosuvastatin reduced Lp-PLA(2) mass
      by 33.8%, Lp-PLA(2) activity by 33.2%, and LDL-C by 48.7% (all P < 0.0001). Among
      those study participants allocated to placebo, increasing quartiles of Lp-PLA(2)
      activity (P(trend) = 0.04) but not Lp-PLA(2) mass (P(trend) = 0.92) were
      associated with incident cardiovascular events after adjustment for LDL-C and
      conventional risk factors. Comparable analyses conducted among those allocated to
      rosuvastatin revealed no significant relationship between Lp-PLA(2) levels and
      subsequent vascular events. The ability of rosuvastatin to reduce vascular events
      was not significantly modified by baseline Lp-PLA(2) level. CONCLUSIONS: Among
      JUPITER trial participants allocated to placebo, levels of Lp-PLA(2) activity,
      but not mass, were associated with cardiovascular risk. However, Lp-PLA(2) no
      longer predicted risk or modified clinical outcomes when participants were
      treated with rosuvastatin.

PMID- 22419751
TI  - Introducing parametric fusion PET/MRI of primary prostate cancer.
AB  - We assessed the performance of parametric fusion PET/MRI based on (11)C-choline
      PET/CT and apparent diffusion coefficient (ADC) maps derived from diffusion
      weighted MRI for the identification of primary prostate cancer. METHODS: (11)C
      choline PET/CT and MRI were performed in 17 patients with untreated primary
      prostate cancer, followed by prostatectomy. Registration of in vivo imaging with
      histology was achieved using a mutual-information objective function and by
      performing ex vivo MRI of the prostatectomy specimen (obtained at 3 T) and whole
      mount sectioning with block-face photography as intermediate steps. Data analysis
      included volumetrically registered whole-mount histology with Gleason scoring,
      (11)C-choline, and ADC data (obtained at 1.5 T). Volumes of interest were defined
      on the basis of histologically proven tumor tissue to calculate tumor-to-benign
      prostate background ratios (TBRs) for (11)C-choline, ADC, and a derived fusion
      PET/MRI parameter calculating the quotient of (11)C-choline over ADC
      (P(CHOL/ADC)). RESULTS: Fifty-one tumor nodules were identified at pathology. The
      TBRs for (11)C-choline (P < 0.05) and P(CHOL/ADC) (P < 0.005) were significantly
      higher in prostate cancers with a Gleason score of >=3 + 4 than with a Gleason
      score of <=3 + 3 disease and controls. For Gleason >= 3 + 4, the ADC TBRs were
      significantly lower than controls and Gleason <= 3 + 3 disease (P < 0.05). The
      absolute value of TBRs obtained from Gleason >= 3 + 4 cancers increased from ADC
      to (11)C-choline PET/CT and from (11)C-choline PET/CT to P(CHOL/ADC), with each
      step being statistically significant. CONCLUSION: Our data indicate that
      parametric PET/MRI using P(CHOL/ADC) improves lesion-to-background contrast
      (TBRs) of Gleason >= 3 + 4 disease, compared with (11)C-choline PET/CT or
      diffusion-weighted MRI, and thus hold promise that parametric imaging performed
      on hybrid PET/MRI may further improve identification and localization of
      significant primary prostate cancer.

PMID- 22419752
TI  - Cost-effectiveness analysis of amino acid PET-guided surgery for supratentorial
      high-grade gliomas.
AB  - High-grade gliomas are brain tumors associated with a devastating prognosis.
      Recent studies have indicated that the combined use of amino acid PET and MRI is
      superior to MRI alone to plan the surgical resection of high-grade gliomas. The
      aim of the study was to analyze the cost-effectiveness of the use of amino acid
      PET for the surgical resection of high-grade gliomas, compared with MRI alone,
      from the perspective of the national health insurance in Germany. METHODS: A
      decision-tree model was set up to compare 2 strategies: the use of MRI alone and
      the combined use of MRI and PET for surgical resection of high-grade gliomas. For
      the analysis, 2 scenarios were calculated: a baseline scenario and a more
      expensive scenario, accounting for disease severity. To test the robustness of
      the results, probabilistic sensitivity analyses using Monte Carlo simulation were
      calculated. RESULTS: Compared with MRI alone, the combined use of MRI and PET
      showed an incremental cost-effectiveness ratio of ?2,948 (?1 ~ U.S.$1.3)per life
      year gained for the baseline scenario and an incremental cost-effectiveness ratio
      of ?4,105 per life-year gained for the admissible-charge-rate scenario. In the
      probabilistic sensitivity analysis in about 60% of the iterations, the combined
      use of PET and MRI was superior to MRI alone when assuming a willingness-to-pay
      threshold of ?30,000. CONCLUSION: The model indicates that the combined use of
      MRI and PET may be cost-effective. The results of this analysis have to be
      considered carefully because there was only limited empiric evidence for several
      input parameters.

PMID- 22419753
TI  - Coronary arterial 18F-FDG uptake by fusion of PET and coronary CT angiography at
      sites of percutaneous stenting for acute myocardial infarction and stable
      coronary artery disease.
AB  - Whether (18)F-FDG PET can detect inflammation in the coronary arteries remains
      controversial. We examined (18)F-FDG uptake at the culprit sites of acute
      myocardial infarction (AMI) after percutaneous coronary stenting (PCS) by
      coregistering PET and coronary CT angiography (CTA). METHODS: Twenty nondiabetic
      patients with AMI (median age, 62 y; 16 men and 4 women) and 7 nondiabetic
      patients with stable coronary artery disease (CAD; median age, 67 y; 4 men and 3
      women) underwent (18)F-FDG PET and coronary CTA 1-6 d after PCS of culprit
      stenoses. After a low-carbohydrate dietary preparation and more than 12 h of
      fasting, 480 MBq of (18)F-FDG were injected, and PET images were acquired 3 h
      later. Helical CTA was performed on a dual-source scanner. Stent position on
      attenuation-correction noncontrast CT and CTA was used to fuse PET and CTA. Two
      experienced readers masked to patient data independently quantified maximum
      target-to-background ratio (maxTBR) at each PCS site. A maxTBR greater than 2.0
      was the criterion for significant uptake. RESULTS: Compared with stable CAD
      patients, more AMI patients exhibited a PCS site maxTBR greater than 2.0 (12/20
      vs. 1/7, P = 0.04). More AMI patients were active smokers (9/20 vs. 0/7 in stable
      CAD, P = 0.03). After adjusting for baseline demographic differences, stent
      myocardium distance, and myocardial (18)F-FDG uptake, presentation of AMI was
      positively associated with a PCS site maxTBR greater than 2.0 (odds ratio, 31.6;
      P = 0.044). Prevalence of excess myocardial (18)F-FDG uptake was similar in both
      populations (8/20 AMI vs. 3/7 stable CAD, P = 0.89). CONCLUSION: Systematic
      fusion of (18)F-FDG PET and coronary CTA demonstrated increased culprit site
      (18)F-FDG uptake more commonly in patients with AMI than in patients with stable
      CAD. However, this approach failed to detect increased signal at the culprit site
      in nearly half of AMI patients, highlighting the challenging nature of in vivo
      coronary artery plaque metabolic imaging. Nonetheless, our findings suggest that
      imaging of coronary artery inflammation is feasible, and further work evaluating
      (18)F-FDG uptake in high-risk coronary plaques prior to rupture would be of great
      interest.

PMID- 22419754
TI  - Tapentadol (Palexia) for moderate to severe acute pain.
AB  - Tapentadol (Palexia - Grunenthal) is a recently introduced strong analgesic with
      u-agonistic opioid and additional noradrenaline reuptake inhibition properties.
      The summary of product characteristics (SPC) states that it is indicated for the
      relief of moderate to severe acute pain in adults, which can be adequately
      managed only with opioid analgesics.1 Here we review the place of tapentadol in
      the treatment of patients with moderate to severe acute pain.

PMID- 22419755
TI  - Topical therapy for scalp psoriasis in adults.
AB  - An estimated 2% of the UK population has psoriasis. For many patients this
      affects the scalp. Particular challenges in managing scalp psoriasis include
      choosing an appropriate treatment option, difficulties of applying topical
      treatments and deciding how to treat severe disease. Moreover, there is a lack of
      good-quality evidence on which to base treatment decisions. Here, we offer some
      practical advice, taking into account the available evidence.

PMID- 22419756
TI  - Capacity and precision in an animal model of visual short-term memory.
AB  - Temporary storage of information in visual short-term memory (VSTM) is a key
      component of many complex cognitive abilities. However, it is highly limited in
      capacity. Understanding the neurophysiological nature of this capacity limit will
      require a valid animal model of VSTM. We used a multiple-item color change
      detection task to measure macaque monkeys' VSTM capacity. Subjects' performance
      deteriorated and reaction times increased as a function of the number of items in
      memory. Additionally, we measured the precision of the memory representations by
      varying the distance between sample and test colors. In trials with similar
      sample and test colors, subjects made more errors compared to trials with highly
      discriminable colors. We modeled the error distribution as a Gaussian function
      and used this to estimate the precision of VSTM representations. We found that as
      the number of items in memory increases the precision of the representations
      decreases dramatically. Additionally, we found that focusing attention on one of
      the objects increases the precision with which that object is stored and degrades
      the precision of the remaining. These results are in line with recent findings in
      human psychophysics and provide a solid foundation for understanding the
      neurophysiological nature of the capacity limit of VSTM.

PMID- 22419758
TI  - An easy method for cutting and fluorescent staining of thin roots.
AB  - BACKGROUND AND AIMS: Cutting plant material is essential for observing internal
      structures and may be difficult for various reasons. Most fixation agents such as
      aldehydes, as well as embedding resins, do not allow subsequent use of
      fluorescent staining and make material too soft to make good-quality hand
      sections. Moreover, cutting thin roots can be very difficult and time consuming.
      A new, fast and effective method to provide good-quality sections and fluorescent
      staining of fresh or fixed root samples, including those of very thin roots (such
      as Arabidopsis or Noccaea), is described here. METHODS: To overcome the above
      mentioned difficulties the following procedure is proposed: fixation in methanol
      (when fresh material cannot be used) followed by en bloc staining with toluidine
      blue, embedding in 6 % agarose, preparation of free-hand sections of embedded
      material, staining with fluorescent dye, and observation in a microscope under UV
      light. KEY RESULTS: Despite eventual slight deformation of primary cell walls
      (depending on the species and root developmental stage), this method allows
      effective observation of different structures such as ontogenetic changes of
      cells along the root axis, e.g. development of xylem elements, deposition of
      Casparian bands and suberin lamellae in endodermis or exodermis or peri
      endodermal thickenings in Noccaea roots. CONCLUSIONS: This method provides good
      quality sections and allows relatively rapid detection of cell-wall
      modifications. Also important is the possibility of using this method for free
      hand cutting of extremely thin roots such as those of Arabidopsis.

PMID- 22419759
TI  - Aquatic adventitious root development in partially and completely submerged
      wetland plants Cotula coronopifolia and Meionectes brownii.
AB  - BACKGROUND AND AIMS: A common response of wetland plants to flooding is the
      formation of aquatic adventitious roots. Observations of aquatic root growth are
      widespread; however, controlled studies of aquatic roots of terrestrial
      herbaceous species are scarce. Submergence tolerance and aquatic root growth and
      physiology were evaluated in two herbaceous, perennial wetland species Cotula
      coronopifolia and Meionectes brownii. METHODS: Plants were raised in large pots
      with 'sediment' roots in nutrient solution and then placed into individual tanks
      and shoots were left in air or submerged (completely or partially). The effects
      on growth of aquatic root removal, and of light availability to submerged plant
      organs, were evaluated. Responses of aquatic root porosity, chlorophyll and
      underwater photosynthesis, were studied. KEY RESULTS: Both species tolerated 4
      weeks of complete or partial submergence. Extensive, photosynthetically active,
      aquatic adventitious roots grew from submerged stems and contributed up to 90 %
      of the total root dry mass. When aquatic roots were pruned, completely submerged
      plants grew less and had lower stem and leaf chlorophyll a, as compared with
      controls with intact roots. Roots exposed to the lowest PAR (daily mean 4.7 +/-
      2.4 umol m(-2) s(-1)) under water contained less chlorophyll, but there was no
      difference in aquatic root biomass after 4 weeks, regardless of light
      availability in the water column (high PAR was available to all emergent shoots).
      CONCLUSIONS: Both M. brownii and C. coronopifolia responded to submergence with
      growth of aquatic adventitious roots, which essentially replaced the existing
      sediment root system. These aquatic roots contained chlorophyll and were
      photosynthetically active. Removal of aquatic roots had negative effects on plant
      growth during partial and complete submergence.

PMID- 22419760
TI  - Tree litter and forest understorey vegetation: a conceptual framework to
      understand the effects of tree litter on a perennial geophyte, Anemone nemorosa.
AB  - BACKGROUND AND AIMS: Litter is a key factor in structuring plant populations,
      through positive or negative interactions. The litter layer forms a mechanical
      barrier that is often strongly selective against individuals lacking hypocotyle
      plasticity. Litter composition also interacts with plant growth by providing
      beneficial nutrients or, inversely, by allowing harmful allelopathic leaching. As
      conspicuous litter fall accumulation is often observed under deciduous forests,
      interactions between tree litter and understorey plant populations are worthy of
      study. METHODS: In a 1-year ex-situ experiment, the effects of tree litter on the
      growth of Anemone nemorosa, a small perennial forest geophyte, were investigated.
      Three 'litter quantity' treatments were defined, representative of forest floor
      litter (199, 356.5 and 514 g m(-2)), which were crossed with five 'litter
      composition' treatments (Quercus petraea, Fagus sylvatica, Carpinus betulus, Q.
      petraea + F. sylvatica and Q. petraea + C. betulus), plus a no-litter control.
      Path analysis was then used to investigate the pathways linking litter
      characteristics and components of adult plant growth. KEY RESULTS: As expected,
      the heavier the litter, the longer the petiole; rhizome growth, however, was not
      depreciated by the litter-induced petiole lengthening. Both rhizome mass
      increment and number of initiated buds marginally increased with the amount of
      litter. Rhizome mass increment was in fact determined primarily by leaf area and
      leaf life span, neither of which was unequivocally correlated with any litter
      characteristics. However, the presence of litter significantly increased leafing
      success: following a late frost event, control rhizomes growing in the absence of
      litter experienced higher leaf mortality before leaf unfolding. CONCLUSIONS: The
      study questions the role of litter as a physical or chemical barrier to ground
      vegetation; to better understand this role, there is a need for ex-situ, longer
      term experiments coupled with in-situ observations in the forest.

PMID- 22419761
TI  - New chloroplast microsatellite markers suitable for assessing genetic diversity
      of Lolium perenne and other related grass species.
AB  - BACKGROUND AND AIMS: Lolium perenne (perennial ryegrass) is the most important
      forage grass species of temperate regions. We have previously released the
      chloroplast genome sequence of L. perenne 'Cashel'. Here nine chloroplast
      microsatellite markers are published, which were designed based on knowledge
      about genetically variable regions within the L. perenne chloroplast genome.
      These markers were successfully used for characterizing the genetic diversity in
      Lolium and different grass species. METHODS: Chloroplast genomes of 14 Poaceae
      taxa were screened for mononucleotide microsatellite repeat regions and primers
      designed for their amplification from nine loci. The potential of these markers
      to assess genetic diversity was evaluated on a set of 16 Irish and 15 European L.
      perenne ecotypes, nine L. perenne cultivars, other Lolium taxa and other grass
      species. KEY RESULTS: All analysed Poaceae chloroplast genomes contained more
      than 200 mononucleotide repeats (chloroplast simple sequence repeats, cpSSRs) of
      at least 7 bp in length, concentrated mainly in the large single copy region of
      the genome. Nucleotide composition varied considerably among subfamilies (with
      Pooideae biased towards poly A repeats). The nine new markers distinguish L.
      perenne from all non-Lolium taxa. TeaCpSSR28 was able to distinguish between all
      Lolium species and Lolium multiflorum due to an elongation of an A(8)
      mononucleotide repeat in L. multiflorum. TeaCpSSR31 detected a considerable
      degree of microsatellite length variation and single nucleotide polymorphism.
      TeaCpSSR27 revealed variation within some L. perenne accessions due to a 44-bp
      indel and was hence readily detected by simple agarose gel electrophoresis.
      Smaller insertion/deletion events or single nucleotide polymorphisms detected by
      these new markers could be visualized by polyacrylamide gel electrophoresis or
      DNA sequencing, respectively. CONCLUSIONS: The new markers are a valuable tool
      for plant breeding companies, seed testing agencies and the wider scientific
      community due to their ability to monitor genetic diversity within breeding
      pools, to trace maternal inheritance and to distinguish closely related species.

PMID- 22419762
TI  - Differential costs of reproduction in females and hermaphrodites in a
      gynodioecious plant.
AB  - BACKGROUND AND AIMS: Plants exhibit a variety of reproductive systems where
      unisexual (females or males) morphs coexist with hermaphrodites. The maintenance
      of dimorphic and polymorphic reproductive systems may be problematic. For
      example, to coexist with hermaphrodites the females of gynodioecious species have
      to compensate for the lack of male function. In our study species, Geranium
      sylvaticum, a perennial gynodioecious herb, the relative seed fitness advantage
      of females varies significantly between years within populations as well as among
      populations. Differences in reproductive investment between females and
      hermaphrodites may lead to differences in future survival, growth and
      reproductive success, i.e. to differential costs of reproduction. Since females
      of this species produce more seeds, higher costs of reproduction in females than
      in hermaphrodites were expected. Due to the higher costs of reproduction, the
      yearly variation in reproductive output of females might be more pronounced than
      that of hermaphrodites. METHODS: Using supplemental hand-pollination of females
      and hermaphrodites of G. sylvaticum we examined if increased reproductive output
      leads to differential costs of reproduction in terms of survival, probability of
      flowering, and seed production in the following year. KEY RESULTS: Experimentally
      increased reproductive output had differential effects on the reproduction of
      females and hermaphrodites. In hermaphrodites, the probability of flowering
      decreased significantly in the following year, whereas in females the costs were
      expressed in terms of decreased future seed production. CONCLUSIONS: When
      combining the probability of flowering and seed production per plant to estimate
      the multiplicative change in fitness, female plants showed a 56 % and
      hermaphrodites showed a 39 % decrease in fitness due to experimentally increased
      reproduction. Therefore, in total, female plants seem to be more sensitive to the
      cost of reproduction in terms of seed fitness than hermaphrodites.

PMID- 22419763
TI  - The genetics of domestication of yardlong bean, Vigna unguiculata (L.) Walp. ssp.
      unguiculata cv.-gr. sesquipedalis.
AB  - BACKGROUND AND AIMS: The genetics of domestication of yardlong bean [Vigna
      unguiculata (L.) Walp. ssp. unguiculata cv.-gr. sesquipedalis] is of particular
      interest because the genome of this legume has experienced divergent
      domestication. Initially, cowpea was domesticated from wild cowpea in Africa; in
      Asia a vegetable form of cowpea, yardlong bean, subsequently evolved from cowpea.
      Information on the genetics of domestication-related traits would be useful for
      yardlong bean and cowpea breeding programmes, as well as comparative genome study
      among members of the genus Vigna. The objectives of this study were to identify
      quantitative trait loci (QTLs) for domestication-related traits in yardlong bean
      and compare them with previously reported QTLs in closely related Vigna. METHODS:
      Two linkage maps were developed from BC(1)F(1) and F(2) populations from the
      cross between yardlong bean (V. unguiculata ssp. unguiculata cv.-gr.
      sesquipedalis) accession JP81610 and wild cowpea (V. unguiculata ssp. unguiculata
      var. spontanea) accession TVnu457. Using these linkage maps, QTLs for 24
      domestication-related traits were analysed and mapped. QTLs were detected for
      traits related to seed, pod, stem and leaf. KEY RESULTS: Most traits were
      controlled by between one and 11 QTLs. QTLs for domestication-related traits show
      co-location on several narrow genomic regions on almost all linkage groups (LGs),
      but especially on LGs 3, 7, 8 and 11. Major QTLs for sizes of seed, pod, stem and
      leaf were principally located on LG7. Pleiotropy or close linkage of genes for
      the traits is suggested in these chromosome regions. CONCLUSIONS: This is the
      first report of QTLs for domestication-related traits in yardlong bean. The
      results provide a foundation for marker-assisted selection of domestication
      related QTLs in yardlong bean and enhance understanding of domestication in the
      genus Vigna.

PMID- 22419764
TI  - The influence of pre- and post-zygotic barriers on interspecific Corymbia
      hybridization.
AB  - BACKGROUND AND AIMS: Corymbia species from different sections hybridize readily,
      with some of increasing economic importance to plantation forestry. This study
      explores the locations of reproductive barriers between interspecific Corymbia
      hybrids and investigates the reproductive success of a wide taxonomic range of C.
      torelliana hybrid crosses. METHODS: Pollen, pistil and embryo development were
      investigated for four C. torelliana crosses (*C. torelliana, *C. citriodora
      subsp. citriodora, *C. tessellaris and *C. intermedia) using fluorescent and
      standard microscopy to identify the locations of interspecific reproductive
      isolating barriers. Corymbia torelliana was also crossed with 16 taxa,
      representing six of the seven Corymbia sections, both Corymbia subgenera and one
      species each from the related genera, Angophora and Eucalyptus. All crosses were
      assessed for capsule and seed yields. KEY RESULTS: Interspecific C. torelliana
      hybridization was controlled by pre-zygotic reproductive isolating barriers
      inhibiting pollen adhesion to the stigma, pollen germination, pollen tube growth
      in the style and pollen tube penetration of the micropyle. Corymbia torelliana
      (subgenus Blakella, sect. Torellianae) was successfully hybridized with Corymbia
      species from subgenus Blakella, particularly C. citriodora subsp. citriodora, C.
      citriodora subsp. variegata, C. henryi (sect. Maculatae) and C. tessellaris
      (sect. Abbreviatae), and subgenus Corymbia, particularly C. clarksoniana and C.
      erythrophloia (sect. Septentrionales). Attempted intergeneric hybrids between C.
      torelliana and either Angophora floribunda or Eucalyptus pellita were
      unsuccessful. CONCLUSIONS: Corymbia hybrids were formed between species from
      different sections and subgenera, but not with species from the related genera
      Angophora or Eucalyptus. Reproductive isolation between the interspecific
      Corymbia hybrid crosses was controlled by early- and late-acting pre-zygotic
      isolating barriers, with reproductive success generally decreasing with
      increasing taxonomic distance between parent species. These findings support the
      monophyly of Corymbia and the close relationships of infrageneric clades. The
      hybridizing propensity of Corymbia species provides opportunities for breeding
      but suggests risks of environmental gene flow.

PMID- 22419765
TI  - Molecular determinants of ligand selectivity for the human multidrug and toxin
      extruder proteins MATE1 and MATE2-K.
AB  - The present study compared the selectivity of two homologous transport proteins,
      multidrug and toxin extruders 1 and 2-K (MATE1 and MATE2-K), and developed three
      dimensional pharmacophores for inhibitory ligand interaction with human MATE1
      (hMATE1). The human orthologs of MATE1 and MATE2-K were stably expressed in
      Chinese hamster ovary cells, and transport function was determined by measuring
      uptake of the prototypic organic cation (OC) substrate 1-methyl-4
      phenylpyridinium (MPP). Both MATEs had similar apparent affinities for MPP, with
      K(tapp) values of 4.4 and 3.7 MUM for MATE1 and MATE2-K, respectively.
      Selectivity was assessed for both transporters from IC(50) values for 59
      structurally diverse compounds. Whereas the two transporters discriminated
      markedly between a few of the test compounds, the IC(50) values for MATE1 and
      MATE2-K were within a factor of 3 for most of them. For hMATE1 there was little
      or no correlation between IC(50) values and the individual molecular descriptors
      LogP, total polar surface area, or pK(a). The IC(50) values were used to generate
      a common-features pharmacophore, quantitative pharmacophores for hMATE1, and a
      bayesian model suggesting molecular features favoring and not favoring the
      interaction of ligands with hMATE1. The models identified hydrophobic regions,
      hydrogen bond donor and hydrogen bond acceptor sites, and an ionizable (cationic)
      feature as key determinants for ligand binding to MATE1. In summary, using a
      combined in vitro and computational approach, MATE1 and MATE2-K were found to
      have markedly overlapping selectivities for a broad range of cationic compounds,
      including representatives from seven novel drug classes of Food and Drug
      Administration-approved drugs.

PMID- 22419767
TI  - Is recent advice on exclusive breastfeeding consistent with the data presented?

PMID- 22419766
TI  - Comment on 'A qualitative approach to Bayes' theorem' by Medow and Lucey.

PMID- 22419768
TI  - In reference to: amoxicillin-clavulanate improves symptoms, reduces treatment
      failure in select children with acute otitis media and increases risk of
      diarrhoea.

PMID- 22419769
TI  - Lifestyle modifications and pharmacotherapy for cardiovascular risk factors are
      associated with improvements in erectile dysfunction.

PMID- 22419770
TI  - Greater diabetes-care contact frequency is associated with more rapid achievement
      of care goals but interpretation of finding requires consideration of patient
      adherence and motivation.

PMID- 22419771
TI  - Thromboprophylaxis in medical inpatients reduces pulmonary embolism, increases
      the risk of major haemorrhage and does not reduce total mortality, producing
      questionable net clinical benefit.

PMID- 22419772
TI  - Mechanisms of reducing postoperative pain, nausea and vomiting: a systematic
      review of current techniques.
AB  - BACKGROUND: Multimodal recovery programmes decrease hospital stay. The objective
      of this systematic review was to assess how single-modality evidence-based care
      principles, regarding postoperative analgesia and postoperative nausea and
      vomiting (PONV) prophylaxis, combine to achieve this. METHODS: A systematic
      review of randomised controlled trials was performed. Relevant trials compared
      postoperative epidural analgesia/parenteral opioid analgesia/paracetamol/non
      steroidal anti-inflammatory drugs (NSAIDs) and postoperative antiemetics. The
      effect on recovery was evaluated in terms of length of hospital stay, pain
      intensity, duration of gastrointestinal dysfunction and incidence of PONV.
      RESULTS: Twenty-three trials were included. Epidural anaesthesia failed to reduce
      length of stay or the incidence of PONV when compared to controls. Pain intensity
      and time to first bowel movement were reduced (p<0.05). Paracetamol did not
      reduce the incidence of PONV. NSAIDs reduced postoperative opioid consumption and
      the incidence of PONV (p<0.05). Dexamethasone and 5-HT3 antagonists reduced the
      incidence of PONV compared to controls. CONCLUSIONS: Epidural anaesthesia appears
      to not reduce length of hospital stay or incidence of PONV despite reducing pain
      intensity and ileus. NSAIDs are more effective than paracetamol in reducing
      postoperative opioid consumption and PONV, while dexamethasone and 5-HT3
      antagonists are both effective in reducing PONV.

PMID- 22419773
TI  - Evolution of radiographic joint damage in rituximab-treated versus TNF-treated
      rheumatoid arthritis cases with inadequate response to TNF antagonists.
AB  - BACKGROUND: Observational studies have suggested that patients with rheumatoid
      arthritis (RA) who experience inadequate response to anti-tumour necrosis factor
      (anti-TNF) agents respond more favourably to rituximab (RTX) than to an
      alternative anti-TNF agent. However, the relative effectiveness of these agents
      on long-term outcomes, particularly in radiographic damage, remains unclear.
      OBJECTIVE: To compare the effectiveness of RTX against anti-TNF agents in
      preventing joint damage in patients with RA who have experienced inadequate
      response to at least one prior anti-TNF agent. METHODS: This is a prospective
      cohort study within the Swiss registry of patients with RA who discontinued at
      least one anti-TNF agent and subsequently received either RTX or an alternative
      anti-TNF agent. The primary outcome, progression of radiographic joint erosions
      (Ratingen erosion score)over time, and the secondary outcome, functional
      disability (Health Assessment Questionnaire Disability Index), were analysed
      using regression models for longitudinal data and adjusted for potential
      confounders. RESULTS: Of the 371 patients included, 104 received RTX and 267
      received an alternative anti-TNF agent. During the 2.6-year median follow-up
      period, the rates of Ratingen erosion score progression were similar between
      patients taking RTX and patients taking an alternative anti-TNF agent (p=0.67).
      The evolution of the Health Assessment Questionnaire score was statistically
      significantly better in the RTX group (p=0.016), but the magnitude of the effect
      was probably not clinically relevant. CONCLUSION: This observational study
      suggests that RTX is as effective as an alternative anti-TNF agent in preventing
      erosions in patients with RA who have previously experienced inadequate response
      to anti-TNF agents.

PMID- 22419774
TI  - Coexistence of hypothyroidism with inflammatory arthritis is associated with
      cardiovascular disease in women.
AB  - OBJECTIVES: Hypothyroidism and inflammatory arthritis tend to coexist, but data
      on this association are sparse. In terms of cardiovascular risk, this association
      may have clinical relevance as this coexistence may carry an additional
      cardiovascular risk. This study calculates, first, the prevalence of
      hypothyroidism in patients with inflammatory arthritis and, second, the
      cardiovascular disease (CVD) prevalence rate in patients with either
      hypothyroidism or inflammatory arthritis, or both. METHODS: Data from the
      Netherlands Information Network of General Practice, a representative Dutch
      sample of 360,000 registered patients, were used. Prevalence rates of
      hypothyroidism were calculated, and multilevel logistic regression analyses were
      used to calculate CVD prevalence rates. RESULTS: Hypothyroidism prevalence was
      6.5% in female patients with arthritis compared to 3.9% in controls (p<0.001).
      CVD prevalence was 4.3% in patients with hypothyroidism, 5.9% in patients with
      inflammatory arthritis, 14.3% in patients with hypothyroid inflammatory arthritis
      and 2.1% in controls. Adjusted CVD prevalence rates were 1.2 (95% CI 0.99 to 1.4)
      for hypothyroidism, 1.5 (95% CI 1.1 to 2.0) for inflammatory arthritis and 3.7
      (95% CI 1.7 to 8.0) for hypothyroid inflammatory arthritis as compared with
      controls. CONCLUSIONS: These data raise awareness on the coexistence of
      hypothyroidism and inflammatory arthritis and emphasise the importance of
      cardiovascular risk management in these patients, particularly when
      hypothyroidism and inflammatory arthritis coexist.

PMID- 22419775
TI  - Responsiveness of EQ-5D and SF-6D in patients with early arthritis: results from
      the ESPOIR cohort.
AB  - OBJECTIVES: The revolution of early aggressive treatments for early arthritis
      (EA) has fuelled the search for better approaches to establishing their cost
      utility ratio. The authors aimed to compare the responsiveness of the EQ-5D and
      the SF-6D in a large prospective cohort of patients with EA. METHODS: EQ-5D and
      SF-6D utility measures were assessed in 813 patients with EA over 2 years.
      Responsiveness was analysed by the standardised response mean (SRM) and effect
      size between baseline and 6, 12 and 24 months for the entire sample and subgroups
      by disease evolution (increase or decrease in Disease Activity Score for 28
      joints). Bootstrap methods were used to estimate 95% CI. RESULTS: The EQ-5D
      provided larger absolute mean change estimates with greater variance than the SF
      6D, whatever the direction of change. At 12 months, the SF-6D was more sensitive
      to change with improved condition than the EQ-5D: SRM 0.83 (0.82 to 0.84) versus
      0.57 (0.56 to 0.58). In contrast, the EQ-5D was more sensitive to change with
      deteriorated condition than the SF-6D: SRM -0.20 (-0.23 to -0.18) versus -0.11 (
      0.14 to -0.08). Results were similar for 6 and 24 months. CONCLUSIONS: The SF-6D
      was more responsive than the EQ-5D with improved EA condition. Confidence in the
      relative cost-effectiveness of two treatments would be better with the SF-6D
      because of its smaller variance. The SF-6D provided more conservative cost
      effectiveness ratios than the EQ-5D and may be more appropriate for trials of
      biological treatments for patients with EA.

PMID- 22419776
TI  - Reduced vitamin D levels are associated with autoimmune response in tuberculosis
      patients.

PMID- 22419777
TI  - Antibodies binding to citrullinated telopeptides of type I and type II collagens
      and to mutated citrullinated vimentin synergistically predict the development of
      seropositive rheumatoid arthritis.
AB  - OBJECTIVE: To assess whether antibodies binding to citrullinated carboxy-terminal
      telopeptides of type I and type II collagens (TELO-I and TELO-II, respectively),
      mutated citrullinated vimentin (MCV) and cyclic citrullinated peptides (CCP)
      predict the development of rheumatoid arthritis (RA). METHODS: A case-control
      study was nested within a Finnish cohort of 36 000 adults who had neither
      arthritis nor a history of arthritis at baseline examination in 1966-1972. Among
      them, 151 subjects developed seropositive (ie, positive for rheumatoid factor)
      RA, and 67 subjects developed seronegative RA by late 1989. One or two control
      subjects were chosen for every case. Preillness serum specimens were analysed for
      antibodies against synthetic TELO-I, TELO-II, MCV and CCP. RESULTS: The mean
      levels of anti-TELO-I, anti-TELO-II, anti-CCP and anti-MCV antibodies were higher
      in subjects who later developed seropositive or seronegative RA than in controls.
      In subjects who later developed seronegative RA, anti-TELO-I and anti-TELO-II
      antibodies were statistically significantly higher compared with controls
      (p=0.005 and p=0.013). In the highest tertiles of anti-MCVs and anti-TELO-I
      levels, the OR for rheumatoid-factor-positive RA were 2.66 (95% CI 1.48 to 4.77)
      or 2.51 (CI 1.48 - 4.28), respectively. The subjects ranked into the highest
      tertiles of both anti-TELO-I and anti-MCV antibodies had a 4.56 OR (95% CI 1.82
      to 11.46) of developing seropositive RA compared with those in the lowest
      tertiles of these antibodies. For the co-occurrence for high anti-TELO-II and
      anti-MCV antibodies, the corresponding OR was 3.62 (95% CI 1.37 to 9.54).
      CONCLUSION: Antibodies to TELO-I or TELO-II and MCV exert a synergistic effect on
      the risk of developing seropositive RA.

PMID- 22419779
TI  - Marketing breast milk substitutes: problems and perils throughout the world.
AB  - On 21 May 1981 the WHO International Code of Marketing Breast Milk Substitutes
      (hereafter referred to as the Code) was passed by 118 votes to 1, the US casting
      the sole negative vote. The Code arose out of concern that the dramatic increase
      in mortality, malnutrition and diarrhoea in very young infants in the developing
      world was associated with aggressive marketing of formula. The Code prohibited
      any advertising of baby formula, bottles or teats and gifts to mothers or
      'bribery' of health workers. Despite successes, it has been weakened over the
      years by the seemingly inexhaustible resources of the global pharmaceutical
      industry. This article reviews the long and tortuous history of the Code through
      the Convention on the Rights of the Child, the HIV pandemic and the rare
      instances when substitute feeding is clearly essential. Currently, suboptimal
      breastfeeding is associated with over a million deaths each year and 10% of the
      global disease burden in children. All health workers need to recognise
      inappropriate advertising of formula, to report violations of the Code and to
      support efforts to promote breastfeeding: the most effective way of preventing
      child mortality throughout the world.

PMID- 22419780
TI  - SEQanswers: an open access community for collaboratively decoding genomes.
AB  - SUMMARY: The affordability of high-throughput sequencing has created an
      unprecedented surge in the use of genomic data in basic, translational and
      clinical research. The rapid evolution of sequencing technology, coupled with its
      broad adoption across biology and medicine, necessitates fast, collaborative
      interdisciplinary discussion. SEQanswers provides a real-time knowledge-sharing
      resource to address this need, covering experimental and computational aspects of
      sequencing and sequence analysis. Developers of popular analysis tools are among
      the >4000 active members, and ~40 peer-reviewed publications have referenced
      SEQanswers. AVAILABILITY: The SEQanswers community is freely accessible at
      http://SEQanswers.com/

PMID- 22419781
TI  - IsoCor: correcting MS data in isotope labeling experiments.
AB  - Mass spectrometry (MS) is widely used for isotopic labeling studies of metabolism
      and other biological processes. Quantitative applications-e.g. metabolic flux
      analysis-require tools to correct the raw MS data for the contribution of all
      naturally abundant isotopes. IsoCor is a software that allows such correction to
      be applied to any chemical species. Hence it can be used to exploit any isotopic
      tracer, from well-known ((13)C, (15)N, (18)O, etc) to unusual ((57)Fe, (77)Se,
      etc) isotopes. It also provides new features-e.g. correction for the isotopic
      purity of the tracer-to improve the accuracy of quantitative isotopic studies,
      and implements an efficient algorithm to process large datasets. Its user
      friendly interface makes isotope labeling experiments more accessible to a wider
      biological community. AVAILABILITY: IsoCor is distributed under OpenSource
      license at http://metasys.insa-toulouse.fr/software/isocor/

PMID- 22419782
TI  - PINALOG: a novel approach to align protein interaction networks--implications for
      complex detection and function prediction.
AB  - MOTIVATION: Analysis of protein-protein interaction networks (PPINs) at the
      system level has become increasingly important in understanding biological
      processes. Comparison of the interactomes of different species not only provides
      a better understanding of species evolution but also helps with detecting
      conserved functional components and in function prediction. Method and RESULTS:
      Here we report a PPIN alignment method, called PINALOG, which combines
      information from protein sequence, function and network topology. Alignment of
      human and yeast PPINs reveals several conserved subnetworks between them that
      participate in similar biological processes, notably the proteasome and
      transcription related processes. PINALOG has been tested for its power in protein
      complex prediction as well as function prediction. Comparison with PSI-BLAST in
      predicting protein function in the twilight zone also shows that PINALOG is
      valuable in predicting protein function. AVAILABILITY AND IMPLEMENTATION: The
      PINALOG web-server is freely available from http://www.sbg.bio.ic.ac.uk/~pinalog.
      The PINALOG program and associated data are available from the Download section
      of the web-server. CONTACT: m.sternberg@imperial.ac.uk SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 22419783
TI  - Harmonization of gene/protein annotations: towards a gold standard MEDLINE.
AB  - MOTIVATION: The recognition of named entities (NER) is an elementary task in
      biomedical text mining. A number of NER solutions have been proposed in recent
      years, taking advantage of available annotated corpora, terminological resources
      and machine-learning techniques. Currently, the best performing solutions combine
      the outputs from selected annotation solutions measured against a single corpus.
      However, little effort has been spent on a systematic analysis of methods
      harmonizing the annotation results and measuring against a combination of Gold
      Standard Corpora (GSCs). RESULTS: We present Totum, a machine learning solution
      that harmonizes gene/protein annotations provided by heterogeneous NER solutions.
      It has been optimized and measured against a combination of manually curated
      GSCs. The performed experiments show that our approach improves the F-measure of
      state-of-the-art solutions by up to 10% (achieving ~70%) in exact alignment and
      22% (achieving ~82%) in nested alignment. We demonstrate that our solution
      delivers reliable annotation results across the GSCs and it is an important
      contribution towards a homogeneous annotation of MEDLINE abstracts. AVAILABILITY
      AND IMPLEMENTATION: Totum is implemented in Java and its resources are available
      at http://bioinformatics.ua.pt/totum

PMID- 22419784
TI  - Predicting the lethal phenotype of the knockout mouse by integrating
      comprehensive genomic data.
AB  - MOTIVATION: The phenotypes of knockout mice provide crucial information for
      understanding the biological functions of mammalian genes. Among various knockout
      phenotypes, lethality is of great interest because those involved genes play
      essential roles. With the availability of large-scale genomic data, we aimed to
      assess how well the integration of various genomic features can predict the
      lethal phenotype of single-gene knockout mice. RESULTS: We first assembled a
      comprehensive list of 491 candidate genomic features derived from diverse data
      sources. Using mouse genes with a known phenotype as the training set, we
      integrated the informative genomic features to predict the knockout lethality
      through three machine learning methods. Based on cross-validation, our models
      could achieve a good performance (accuracy = 73% and recall = 63%). Our results
      serve as a valuable practical resource in the mouse genetics research community,
      and also accelerate the translation of the knowledge of mouse genes into better
      strategies for studying human disease.

PMID- 22419785
TI  - SAMSCOPE: an OpenGL-based real-time interactive scale-free SAM viewer.
AB  - SUMMARY: Existing SAM visualization tools like 'samtools tview' (Li et al., 2009)
      are limited to a small region of the genome, and tools like Tablet (Milne et al.,
      2010) are limited to a relatively small number of reads and may fail outright on
      large datasets. We need to visualize complex ChIP-Seq and RNA-Seq features such
      as polarity as well as coverage across whole 3 Gbp genomes such as Human. We have
      addressed these problems in a lightweight visualization system called SAMSCOPE
      accelerated by OpenGL. The extensive pre-processing and fast OpenGL interface of
      SAMSCOPE provides instantaneous and intuitive browsing of complex data at all
      levels of detail across multiple experiments. AVAILABILITY AND IMPLEMENTATION:
      The SAMSCOPE software, implemented in C++ for Linux, with source code, binary
      packages and documentation are freely available from
      http://samscope.dna.bio.keio.ac.jp.

PMID- 22419786
TI  - Fulcrum: condensing redundant reads from high-throughput sequencing studies.
AB  - MOTIVATION: Ultra-high-throughput sequencing produces duplicate and near
      duplicate reads, which can consume computational resources in downstream
      applications. A tool that collapses such reads should reduce storage and assembly
      complications and costs. RESULTS: We developed Fulcrum to collapse identical and
      near-identical Illumina and 454 reads (such as those from PCR clones) into single
      error-corrected sequences; it can process paired-end as well as single-end reads.
      Fulcrum is customizable and can be deployed on a single machine, a local network
      or a commercially available MapReduce cluster, and it has been optimized to
      maximize ease-of-use, cross-platform compatibility and future scalability.
      Sequence datasets have been collapsed by up to 71%, and the reduced number and
      improved quality of the resulting sequences allow assemblers to produce longer
      contigs while using less memory.

PMID- 22419787
TI  - Female genital mutilation: the role of health professionals in prevention,
      assessment, and management.

PMID- 22419788
TI  - Acute Charcot foot.

PMID- 22419789
TI  - Hospitals: what do they do and how much does it cost?

PMID- 22419790
TI  - Severe human rights abuses in healthcare settings.

PMID- 22419791
TI  - BMJ invokes new Texan freedom of speech law to fight Wakefield libel case.

PMID- 22419792
TI  - US focus on new psychiatric disorders is distracting attention from tackling
      global mental health problems.

PMID- 22419793
TI  - TachoSil for postinfarction ventricular free wall rupture.
AB  - Despite a decline in the last three decades, postinfarction ventricular free wall
      rupture still complicates more than 3% of acute ST-elevation myocardial
      infarctions and remains a surgical challenge. TachoSil (Nycomed, Zurich,
      Switzerland) is an equine collagen patch coated with human fibrinogen and human
      thrombin, which has recently been used for haemostasis in cardiovascular surgery,
      but its potential usefulness in free wall rupture has not been reported. Initial
      clinical experience with an on-pump sutureless technique without cardioplegia,
      using wide TachoSil patching to achieve free wall rupture repair, has been
      described.

PMID- 22419778
TI  - Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic
      dose responses.
AB  - For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged
      traditional concepts in toxicology, in particular the dogma of "the dose makes
      the poison," because EDCs can have effects at low doses that are not predicted by
      effects at higher doses. Here, we review two major concepts in EDC studies: low
      dose and nonmonotonicity. Low-dose effects were defined by the National
      Toxicology Program as those that occur in the range of human exposures or effects
      observed at doses below those used for traditional toxicological studies. We
      review the mechanistic data for low-dose effects and use a weight-of-evidence
      approach to analyze five examples from the EDC literature. Additionally, we
      explore nonmonotonic dose-response curves, defined as a nonlinear relationship
      between dose and effect where the slope of the curve changes sign somewhere
      within the range of doses examined. We provide a detailed discussion of the
      mechanisms responsible for generating these phenomena, plus hundreds of examples
      from the cell culture, animal, and epidemiology literature. We illustrate that
      nonmonotonic responses and low-dose effects are remarkably common in studies of
      natural hormones and EDCs. Whether low doses of EDCs influence certain human
      disorders is no longer conjecture, because epidemiological studies show that
      environmental exposures to EDCs are associated with human diseases and
      disabilities. We conclude that when nonmonotonic dose-response curves occur, the
      effects of low doses cannot be predicted by the effects observed at high doses.
      Thus, fundamental changes in chemical testing and safety determination are needed
      to protect human health.

PMID- 22419794
TI  - Absence of posterior tricuspid valve leaflet and valve reconstruction.
AB  - We report a rare case of the absence of a posterior tricuspid valve leaflet. A
      male patient, aged 46, suffering from severe tricuspid valve regurgitation (TR)
      of unknown aetiology and atrial septal aneurysm was referred to our hospital for
      surgery. On surgical inspection, the posterior tricuspid valve leaflet and its
      subvalvular apparatus were completely absent and only the valve annulus was seen
      in the corresponding position. The anterior and septal leaflets were normal. We
      successfully reconstructed the tricuspid valve as follows: the head of an
      anterior papillary muscle was approximated to the ventricular septum (Sebening
      stitch). After the approximation of the centre of the tricuspid annulus of the
      anterior leaflet to the tricuspid annulus on the opposite side, a sizer of 29 mm
      in diameter was easily passed through the anterior orifice. The posterior orifice
      was closed with running sutures (posterior annulorrhaphy after Hetzer). Before
      these procedures, we attempted to reconstruct the tricuspid valve with a
      posterior annulorrhaphy alone; however, valve competence was insufficient. A
      Sebening stitch was necessary to improve the valve competence. Echocardiography
      showed TR grade 1 at the patient's discharge from hospital and TR grade 1 to 2 at
      the follow-up, 10 months after the operation.

PMID- 22419795
TI  - Lung cancer staging: a physiological update.
AB  - The tumour-node metastasis (TNM) classification system is anatomically based. We
      investigated whether the addition of simple physiological variables, age and body
      mass index (BMI), would affect survival curves, i.e. a composite anatomical and
      physiological staging system. We retrospectively analysed a prospectively
      validated thoracic surgery database (n = 1981). Cox multivariate analysis was
      performed to determine possible significant factors. Kaplan-Meier survival curves
      were constructed with combined anatomical and physiological factors. Cox
      multivariate analysis revealed age (P < 0.001) and BMI (P = 0.01) as significant
      factors affecting survival. Receiver operating curve analysis determined cut-off
      levels for age of 67 and BMI of 27.6. A composite anatomical and physiological
      survival curve based on TNM for BMI > 27.6 and age < 67 was produced. Age and BMI
      criteria resulted in significantly different survival curves, for stage I (P <
      0.0001) and stage II (P = 0.0032), but not for stage III (P = 0.06). Neural
      network analysis confirmed the importance of BMI and age above cancer stage with
      regard to long-term survival. Combining age < 67, BMI > 27.6 and TNM anatomical
      classification results in very different estimated survival curves from the usual
      TNM system. Patients from stages I, II and III may have survival equivalent to a
      stage higher or lower depending on their age and BMI.

PMID- 22419796
TI  - Impact of previous gastrectomy on postoperative pneumonia after pulmonary
      resection in lung cancer patients.
AB  - Postoperative pneumonia is a serious complication following pulmonary resection.
      Aspiration of oesophageal reflux contents is known to cause pulmonary
      complications in patients with a history of gastrectomy. In this study, we
      compared the incidence of postoperative pneumonia in patients with or without
      previous gastrectomy. A retrospective review was conducted of clinical charts for
      patients who underwent radical pulmonary resection for non-small cell lung cancer
      from January 2006 to December 2010. Pneumonia was diagnosed with chest computed
      tomography findings in all cases. A total of 333 patients underwent pulmonary
      resections during the study period. Twenty-seven patients (8.1%) had a history of
      gastrectomy. Eight patients (2.2%) had postoperative pneumonia. All eight
      patients who developed postoperative pneumonia did not have pneumonia before
      pulmonary resection. Of the aforementioned 27 patients, five (18.5%) developed
      pneumonia postoperatively, whereas only three of 325 patients who did not have a
      history of gastrectomy (0.9%) had pneumonia (P < 0.001). In multivariate
      analysis, a history of gastrectomy had the highest impact on the odds ratio
      (8.81) for postoperative pneumonia. A significantly higher incidence of
      postoperative pneumonia was found in patients with a history of gastrectomy.
      Prophylactic treatment, such as premedication with ranitidine, should be
      considered in those patients.

PMID- 22419797
TI  - How effective is unipolar radiofrequency ablation for atrial fibrillation during
      concomitant cardiac surgery?
AB  - A best evidence topic in cardiothoracic surgery was written according to a
      structured protocol. The question addressed was whether in patients undergoing
      cardiac surgery, concomitant unipolar radiofrequency ablation had a sufficiently
      acceptable success rate to justify the additional procedure. A total of 256
      papers were found using the reported search; of which, 9 represented the best
      evidence to answer the clinical question. The authors, journal, date and country
      of publication, patient group studied, study type, relevant outcomes and results
      of these papers were tabulated. Major exclusion criteria included studies using
      bipolar ablation, ambiguous or unspecified ablation techniques, other energy
      modalities and studies with highly variable or undisclosed follow-up time. All of
      the studies showed concomitant unipolar ablation to have an acceptable success
      rate in restoring patients to sinus rhythm (SR), with follow-ups ranging from 12
      months to 5 years. At 12-month follow-up, one study showed that this rate was as
      high as 83%. Ablations were more likely to be successful in patients with
      paroxysmal or persistent atrial fibrillation (AF) as defined by ACC/AHA/ESC
      criteria. One paper showed that paroxysmal/persistent AF at baseline was
      predictive of likely success of ablation in patients with permanent AF (P =
      0.0004). Restoration and maintenance of SR after ablation was not significantly
      affected by the type of cardiac surgery performed (P = 0.262). Unipolar ablation
      does have limitations such as high tissue temperature and no predictable
      transmurality. However, it appears to compare favourably in the long term to
      energy modalities such as microwave. The lack of level I evidence was a major
      drawback in the analysis, as was the lack of continuous electrocardiogram
      monitoring in the methodology of the studies. Figures quoted from the data could
      therefore be under-representations of the true instances of AF recurrence. With
      the current evidence, concomitant ablation to treat AF during cardiac surgery
      appears safe in terms of adding no additional risks, and effective at restoring
      SR regardless of the type of cardiac surgery. This is particularly true of
      younger patients with paroxysmal or persistent AF and those with smaller atrial
      diameters.

PMID- 22419798
TI  - External fistulous wound with Pseudomonas aeruginosa infection and massive
      bleeding following rupture of pulmonary suppuration.
AB  - We present a 54-year old man with a pulmonary infectious cavity continuing to a
      cutaneous fistula. Before he was admitted to our hospital, he had undergone open
      window surgery for a left thoracic empyema due to the rupture of pulmonary
      suppuration of the left upper lobe. He had then undergone thoracoplasty with the
      plombage of the cavity using left pectoralis major muscle. However, this
      procedure had failed and the external fistulous wound remained infected by
      Pseudomonas aeruginosa and occasional massive bleeding from the cavity occurred.
      He underwent en bloc left upper lobectomy for the external fistulous wound. The
      pedicled left latissimus dorsi muscle flap was transposed to fill the dead space
      and reinforce the bronchial stump. He remained in good health and did not
      experience intrathoracic infection or haemoptysis.

PMID- 22419799
TI  - Plasmid-encoded PER-7 beta-lactamase responsible for ceftazidime resistance in
      Acinetobacter baumannii isolated in the United Arab Emirates.
AB  - OBJECTIVES: To investigate the mechanism of ceftazidime resistance in two
      isogenic Acinetobacter baumannii strains from the United Arab Emirates. METHODS:
      Two A. baumannii strains, NM55 and NM128, were isolated 4 months apart from a 6
      year-old patient in the United Arab Emirates. Genotypic characterization was
      performed by PFGE and the MIC of ceftazidime was determined by the agar dilution
      method. Detection of bla(OXA) and metallo-beta-lactamase genes was performed by
      multiplex PCR. Analysis of bla(PER-7), ISAba1, bla(ADC) and the ISCR1 element was
      carried out by standard PCR. Plasmid analysis was achieved by Southern blotting.
      RESULTS: Strain NM55 was resistant to ceftazidime, whereas strain NM128 was
      susceptible. Both isolates carried the bla(OXA-23) and bla(OXA-64) genes and were
      identical according to their PFGE patterns. ISAba1 was present upstream of the
      bla(OXA-23) gene, but absent upstream of bla(ADC-26), in both strains. Strain
      NM55 possessed a bla(PER-7) gene with the presence of gst, a fragment of the abc
      transporter and a transposase gene downstream of it. The entire structure was
      part of an ISCR1 element and was located on an ~ 200 kb plasmid in strain NM55,
      while the ceftazidime-susceptible NM128 strain carried an ~ 180 kb plasmid
      without the bla(PER-7) gene. CONCLUSIONS: Ceftazidime resistance was mediated by
      a PER-7 beta-lactamase encoded in an ISCR1 element located on a plasmid. This
      represents the first detection of a PER-7 beta-lactamase encoded by a plasmid in
      A. baumannii.

PMID- 22419800
TI  - Eliminating waste in US health care.
AB  - The need is urgent to bring US health care costs into a sustainable range for
      both public and private payers. Commonly, programs to contain costs use cuts,
      such as reductions in payment levels, benefit structures, and eligibility. A less
      harmful strategy would reduce waste, not value-added care. The opportunity is
      immense. In just 6 categories of waste--overtreatment, failures of care
      coordination, failures in execution of care processes, administrative complexity,
      pricing failures, and fraud and abuse--the sum of the lowest available estimates
      exceeds 20% of total health care expenditures. The actual total may be far
      greater. The savings potentially achievable from systematic, comprehensive, and
      cooperative pursuit of even a fractional reduction in waste are far higher than
      from more direct and blunter cuts in care and coverage. The potential economic
      dislocations, however, are severe and require mitigation through careful
      transition strategies.

PMID- 22419801
TI  - The magnitude of dengue virus NS1 protein secretion is strain dependent and does
      not correlate with severe pathologies in the mouse infection model.
AB  - There are conflicting data on the relationship between the level of secreted NS1
      (sNS1), viremia, and disease severity upon dengue virus (DENV) infection in the
      clinical setting, and therefore, we examined this relationship in the widely
      accepted AG129 mouse model. Because of the failure of a routinely used NS1
      detection kit to detect sNS1 of the mouse-adapted DENV2 strain, we screened 15
      previously undescribed NS1 monoclonal antibodies and developed a robust capture
      enzyme-linked immunosorbent assay (ELISA) with detection sensitivity at the low
      nanogram level (0.2 ng/ml) using recombinant baculovirus-expressed sNS1 as well
      as sNS1 that was immunoaffinity purified from the various DENV2 strains employed
      in this study. Using this test, we demonstrated that increased viremia paralleled
      severe pathologies; however, sNS1 level did not correlate with viremia or
      severity. Furthermore, among the DENV2 strains that were tested, the level of NS1
      secretion did not correspond to virus replication rate in vitro, at the cellular
      level. Together, our data indicate that the magnitude of NS1 secretion appears to
      be strain dependent and does not correlate with viral virulence in the AG129
      mouse model.

PMID- 22419802
TI  - HIV-2 genome dimerization is required for the correct processing of Gag: a second
      site reversion in matrix can restore both processes in dimerization-impaired
      mutant viruses.
AB  - A unique feature of retroviruses is the packaging of two copies of their genome,
      noncovalently linked at their 5' ends. In vitro, dimerization of human
      immunodeficiency virus type 2 (HIV-2) RNA occurs by interaction of a self
      complementary sequence exposed in the loop of stem-loop 1 (SL-1), also termed the
      dimer initiation site (DIS). However, in virions, HIV-2 genome dimerization does
      not depend on the DIS. Instead, a palindrome located within the packaging signal
      (Psi) is the essential motif for genome dimerization. We reported previously that
      a mutation within Psi decreasing genome dimerization and packaging also resulted
      in a reduced proportion of mature particles (A. L'Hernault, J. S. Greatorex, R.
      A. Crowther, and A. M. Lever, Retrovirology 4:90, 2007). In this study, we
      investigated further the relationship between HIV-2 genome dimerization, particle
      maturation, and infectivity by using a series of targeted mutations in SL-1. Our
      results show that disruption of a purine-rich ((392)-GGAG-(395)) motif within Psi
      causes a severe reduction in genome dimerization and a replication defect.
      Maintaining the extended SL-1 structure in combination with the (392)-GGAG-(395)
      motif enhanced packaging. Unlike that of HIV-1, which can replicate despite
      mutation of the DIS, HIV-2 replication depends critically on genome dimerization
      rather than just packaging efficiency. Gag processing was altered in the HIV-2
      dimerization mutants, resulting in the accumulation of the MA-CA-p2 processing
      intermediate and suggesting a link between genome dimerization and particle
      assembly. Analysis of revertant SL-1 mutant viruses revealed that a compensatory
      mutation in matrix (70TI) could rescue viral replication and partially restore
      genome dimerization and Gag processing. Our results are consistent with
      interdependence between HIV-2 RNA dimerization and the correct proteolytic
      cleavage of the Gag polyprotein.

PMID- 22419803
TI  - Analysis of clinical ostreid herpesvirus 1 (Malacoherpesviridae) specimens by
      sequencing amplified fragments from three virus genome areas.
AB  - Although there are a number of ostreid herpesvirus 1 (OsHV-1) variants, it is
      expected that the true diversity of this virus will be known only after the
      analysis of significantly more data. To this end, we analyzed 72 OsHV-1
      "specimens" collected mainly in France over an 18-year period, from 1993 to 2010.
      Additional samples were also collected in Ireland, the United States, China,
      Japan, and New Zealand. Three virus genome regions (open reading frame 4 [ORF4],
      ORF35, -36, -37, and -38, and ORF42 and -43) were selected for PCR analysis and
      sequencing. Although ORF4 appeared to be the most polymorphic genome area,
      distinguishing several genogroups, ORF35, -36, -37, and -38 and ORF42 and -43
      also showed variations useful in grouping subpopulations of this virus.

PMID- 22419804
TI  - The Autographa californica M nucleopolyhedrovirus ac79 gene encodes an early gene
      product with structural similarities to UvrC and intron-encoded endonucleases
      that is required for efficient budded virus production.
AB  - The Autographa californica M nucleopolyhedrovirus (AcMNPV) orf79 (ac79) gene is a
      conserved gene in baculoviruses and shares homology with genes in ascoviruses,
      iridoviruses, and several bacteria. Ac79 has a conserved motif and structural
      similarities to UvrC and intron-encoded endonucleases. Ac79 is produced at early
      times during infection and concentrates in the nucleus of infected cells at late
      times, suggesting a cellular compartment-specific function. To investigate its
      function, an ac79-knockout bacmid was generated through homologous recombination
      in Escherichia coli. Titration assays showed that budded virus (BV) production
      was reduced in the ac79-knockout virus compared to control viruses, following
      either virus infection or the transfection of bacmid DNA. The ac79-knockout virus
      infected cells produced plaques smaller than those infected with control ac79
      carrying viruses. No obvious differences were observed in viral DNA synthesis,
      viral protein accumulation, or the formation of occlusion bodies in ac79-knockout
      and control viral DNA-transfected cells, indicating progression into the late and
      very late phases of viral infection. However, comparative analyses of the amounts
      of BV genomic DNA and structural proteins in a given quantity of infectious
      virions suggested that the ac79-knockout virus produced more noninfectious BV in
      infected cells than the control virus. The structure of the ac79-knockout BV
      determined by transmission electron microscopy appeared to be similar to that of
      the control virus, although aberrant capsid protein-containing tubular structures
      were observed in the nuclei of ac79-knockout virus-infected cells. Tubular
      structures were not observed for ac79 viruses with mutations in conserved
      endonuclease residues. These results indicate that Ac79 is required for efficient
      BV production.

PMID- 22419805
TI  - Removal of vaccinia virus genes that block interferon type I and II pathways
      improves adaptive and memory responses of the HIV/AIDS vaccine candidate NYVAC-C
      in mice.
AB  - Poxviruses encode multiple inhibitors of the interferon (IFN) system, acting at
      different levels and blocking the induction of host defense mechanisms. Two viral
      gene products, B19 and B8, have been shown to act as decoy receptors of type I
      and type II IFNs, blocking the binding of IFN to its receptor. Since IFN plays a
      major role in innate immune responses, in this investigation we asked to what
      extent the viral inhibitors of the IFN system impact the capacity of poxvirus
      vectors to activate immune responses. This was tested in a mouse model with
      single and double deletion mutants of the vaccine candidate NYVAC-C, which
      expresses the HIV-1 Env, Gag, Pol, and Nef antigens. When deleted individually or
      in double, the type I (B19) and type II (B8) IFN binding proteins were not
      required for virus replication in cultured cells. Studies of immune responses in
      mice after DNA prime/NYVAC boost revealed that deletion of B8R and/or B19R genes
      improved the magnitude and quality of HIV-1-specific CD8(+) T cell adaptive
      immune responses and impacted their memory phase, changing the contraction, the
      memory differentiation, the effect magnitude, and the functionality profile. For
      B cell responses, deletion of the viral gene B8R and/or B19R had no effect on
      antibody levels to HIV-1 Env. These findings revealed that single or double
      deletion of viral factors (B8 and B19) targeting the IFN pathway is a useful
      approach in the design of improved poxvirus-based vaccines.

PMID- 22419806
TI  - The amino terminus of the vaccinia virus E3 protein is necessary to inhibit the
      interferon response.
AB  - Vaccinia virus (VACV) encodes a multifunctional protein, E3L, that is necessary
      for interferon (IFN) resistance in cells in culture. Interferon resistance has
      been mapped to the well-characterized carboxy terminus of E3L, which contains a
      conserved double-stranded RNA binding domain. The amino terminus of E3L has a Z
      form nucleic acid binding domain, which has been shown to be dispensable for
      replication and IFN resistance in HeLa and RK13 cells; however, a virus
      expressing E3L deleted of the amino terminus has reduced pathogenicity in an
      animal model. In this study, we demonstrate that the pathogenicity of a virus
      expressing E3L deleted of the amino terminus was fully rescued in type I IFN
      receptor knockout (IFN-alpha/betaR(-/-)) mice. Furthermore, this virus was IFN
      sensitive in primary mouse embryo fibroblasts (MEFs). This virus induced the
      phosphorylation of the alpha subunit of eukaryotic initiation factor 2
      (eIF2alpha) in MEFs in an IFN-dependent manner. The depletion of double-stranded
      RNA-dependent protein kinase (PKR) from these MEFs restored the IFN resistance of
      this virus. Furthermore, the virus expressing E3L deleted of the amino terminus
      was also IFN resistant in PKR(-/-) MEFs. Thus, our data demonstrate that the
      amino terminus of E3L is necessary to inhibit the type I IFN response both in
      mice and in MEFs and that in MEFs, the amino terminus of E3L functions to inhibit
      the PKR pathway.

PMID- 22419807
TI  - Identification of host-chromosome binding sites and candidate gene targets for
      Kaposi's sarcoma-associated herpesvirus LANA.
AB  - LANA is essential for tethering the Kaposi's sarcoma-associated herpesvirus
      (KSHV) genome to metaphase chromosomes and for modulating host-cell gene
      expression, but the binding sites in the host-chromosome remain unknown. Here, we
      use LANA-specific chromatin immunoprecipitation coupled with high-throughput
      sequencing (ChIP-Seq) to identify LANA binding sites in the viral and host-cell
      genomes of a latently infected pleural effusion lymphoma cell line BCBL1. LANA
      bound with high occupancy to the KSHV genome terminal repeats (TR) and to a few
      minor binding sites in the KSHV genome, including the LANA promoter region. We
      identified 256 putative LANA binding site peaks with P < 0.01 and overlap in two
      independent ChIP-Seq experiments. We validated several of the high-occupancy
      binding sites by conventional ChIP assays and quantitative PCR. Candidate
      cellular LANA binding motifs were identified and assayed for binding to purified
      recombinant LANA protein in vitro but bound with low affinity compared to the
      viral TR binding site. More than half of the LANA binding sites (170/256) could
      be mapped to within 2.5 kb of a cellular gene transcript. Pathways and Gene
      Ontogeny (GO) analysis revealed that LANA binds to genes within the p53 and tumor
      necrosis factor (TNF) regulatory network. Further analysis revealed partial
      overlap of LANA and STAT1 binding sites in several gamma interferon (IFN-gamma)
      regulated genes. We show that ectopic expression of LANA can downmodulate IFN
      gamma-mediated activation of a subset of genes, including the TAP1 peptide
      transporter and proteasome subunit beta type 9 (PSMB9), both of which are
      required for class I antigen presentation. Our data provide a potential mechanism
      through which LANA may regulate several host cell pathways by direct binding to
      gene regulatory elements.

PMID- 22419808
TI  - Selection pressure on HIV-1 envelope by broadly neutralizing antibodies to the
      conserved CD4-binding site.
AB  - The monoclonal antibody (MAb) VRC01 was isolated from a slowly progressing HIV-1
      infected donor and was shown to neutralize diverse HIV-1 strains by binding to
      the conserved CD4 binding site (CD4bs) of gp120. To better understand the
      virologic factors associated with such antibody development, we characterized HIV
      1 envelope (Env) variants from this donor and five other donors who developed
      broadly neutralizing antibodies. A total of 473 env sequences were obtained by
      single-genome amplification, and 100 representative env clones were expressed and
      tested for entry and neutralization sensitivity. While VRC01 neutralizes about
      90% of the genetically diverse heterologous HIV-1 strains tested, only selective
      archival Env variants from the VRC01 donor were sensitive to VRC01 and all of the
      Env variants derived from the donor plasma were resistant, indicating strong
      antibody-based selection pressure. Despite their resistance to this broadly
      reactive MAb that partially mimics CD4, all Env variants required CD4 for entry.
      Three other CD4bs MAbs from the same donor were able to neutralize some VRC01
      escape variants, suggesting that CD4bs antibodies continued to evolve in response
      to viral escape. We also observed a relatively high percentage of VRC01-resistant
      Env clones in the plasma of four of five additional broadly neutralizing donors,
      suggesting the presence of CD4bs-directed neutralizing antibodies in these
      donors. In total, these data indicate that the CD4bs-directed neutralizing
      antibodies exert ongoing selection pressure on the conserved CD4bs epitope of HIV
      1 Env.

PMID- 22419809
TI  - Transformation by E1A oncoprotein involves ubiquitin-mediated proteolysis of the
      neuronal and tumor repressor REST in the nucleus.
AB  - The adenovirus early region 1A (E1A) protein promotes cell immortalization and
      transformation by mediating the activities of key cellular regulators. The
      repressor element 1-silencing transcription factor (REST), which is a major
      neuronal and tumor suppressor, was previously found mainly in the cytoplasm
      rather than in the nuclei of adenovirus-transformed rodent cells (22). We now
      demonstrate that the loss of REST in the nucleus is due to its rapid degradation
      by the ubiquitin-proteasome system. Only nuclear REST, but not its cytoplasmic
      counterpart, was ubiquitinated and degraded. REST degradation was blocked by the
      ubiquitination inhibitor PYR-41 and the proteasome inhibitor MG-132 but not by
      the nuclear export inhibitor leptomycin B. REST degradation required both of its
      two C-terminal degrons that are recognized by the ubiquitin ligase SCF(beta
      TrCP), since deletion or mutation of either degron eliminated degradation.
      Importantly, E1A was shown to mediate REST ubiquitination and degradation by
      upregulating beta-TrCP. Knockdown of E1A in virus-transformed cells reduced both
      beta-TrCP and ubiquitination of nuclear REST. In contrast, when expressed in HeLa
      cells, E1A enhanced the degradation of nuclear REST. Reconstitution of REST in
      virus-transformed cells negatively affected E1A-mediated cell proliferation and
      anchorage-independent growth. These data strongly indicate that E1A stimulates
      ubiquitination and proteolysis of REST in the nucleus, thereby abolishing the
      tumor suppressor functions of REST.

PMID- 22419810
TI  - Virus inhibition activity of effector memory CD8(+) T cells determines simian
      immunodeficiency virus load in vaccinated monkeys after vaccine breakthrough
      infection.
AB  - The goal of an effective AIDS vaccine is to generate immunity that will prevent
      human immunodeficiency virus 1 (HIV-1) acquisition. Despite limited progress
      toward this goal, renewed optimism has followed the recent success of the RV144
      vaccine trial in Thailand. However, the lack of complete protection in this trial
      suggests that breakthroughs, where infection occurs despite adequate vaccination,
      will be a reality for many vaccine candidates. We previously reported that
      neutralizing antibodies elicited by DNA prime-recombinant adenovirus serotype 5
      (rAd5) boost vaccination with simian immunodeficiency virus strain mac239
      (SIVmac239) Gag-Pol and Env provided protection against pathogenic SIVsmE660
      acquisition after repeated mucosal challenge. Here, we report that SIV-specific
      CD8(+) T cells elicited by that vaccine lowered both peak and set-point viral
      loads in macaques that became infected despite vaccination. These SIV-specific
      CD8(+) T cells showed strong virus-inhibitory activity (VIA) and displayed an
      effector memory (EM) phenotype. VIA correlated with high levels of CD107a
      mobilization and perforin expression in SIV-specific CD8(+) T cells. Remarkably,
      both the frequency and the number of Gag CM9-specific public clonotypes were
      strongly correlated with VIA mediated by EM CD8(+) T cells. The ability to elicit
      such virus-specific EM CD8(+) T cells might contribute substantially to an
      efficacious HIV/AIDS vaccine, even after breakthrough infection.

PMID- 22419811
TI  - Modified vaccinia virus Ankara-based vaccine vectors induce apoptosis in
      dendritic cells draining from the skin via both the extrinsic and intrinsic
      caspase pathways, preventing efficient antigen presentation.
AB  - Dendritic cells (DC) are potent antigen-presenting cells and central to the
      induction of immune responses following infection or vaccination. The collection
      of DC migrating from peripheral tissues by cannulation of the afferent lymphatic
      vessels provides DC which can be used directly ex vivo without extensive in vitro
      manipulations. We have previously used bovine migrating DC to show that
      recombinant human adenovirus 5 vectors efficiently transduce afferent lymph
      migrating DEC-205(+) CD11c(+) CD8(-) DC (ALDC). We have also shown that
      recombinant modified vaccinia virus Ankara (MVA) infects ALDC in vitro, causing
      downregulation of costimulatory molecules, apoptosis, and cell death. We now show
      that in the bovine system, modified vaccinia virus Ankara-induced apoptosis in DC
      draining from the skin occurs soon after virus binding via the caspase 8 pathway
      and is not associated with viral gene expression. We also show that after virus
      entry, the caspase 9 pathway cascade is initiated. The magnitude of T cell
      responses to mycobacterial antigen 85A (Ag85A) expressed by recombinant MVA
      infected ALDC is increased by blocking caspase-induced apoptosis. Apoptotic
      bodies generated by recombinant MVA (rMVA)-Ag85A-infected ALDC and containing
      Ag85A were phagocytosed by noninfected migrating ALDC expressing SIRPalpha via
      actin-dependent phagocytosis, and these ALDC in turn presented antigen. However,
      the addition of fresh ALDC to MVA-infected cultures did not improve on the
      magnitude of the T cell responses; in contrast, these noninfected DC showed
      downregulation of major histocompatibility complex class II (MHC-II), CD40, CD80,
      and CD86. We also observed that MVA-infected ALDC promoted migration of DEC
      205(+) SIRPalpha(+) CD21(+) DC as well as CD4(+) and CD8(+) T cells independently
      of caspase activation. These in vitro studies show that induction of apoptosis in
      DC by MVA vectors is detrimental to the subsequent induction of T cell responses.

PMID- 22419812
TI  - MicroRNA targeting of neurotropic flavivirus: effective control of virus escape
      and reversion to neurovirulent phenotype.
AB  - Neurotropic flaviviruses can efficiently replicate in the developing and mature
      central nervous systems (CNS) of mice causing lethal encephalitis. Insertion of a
      single copy of a target for brain-expressed microRNAs (miRNAs) in the 3'
      noncoding region (3'NCR) of the flavivirus genome (chimeric tick-borne
      encephalitis virus/dengue virus) abolished virus neurovirulence in the mature
      mouse CNS. However, in the developing CNS of highly permissive suckling mice, the
      miRNA-targeted viruses can revert to a neurovirulent phenotype by accumulating
      deletions or mutations within the miRNA target sequence. Virus escape from miRNA
      mediated suppression in the developing CNS was markedly diminished by increasing
      the number of miRNA target sites and by extending the distance between these
      sites in the virus genome. Insertion of multiple miRNA targets into the 3'NCR
      altered virus neuroinvasiveness, decreased neurovirulence and neuroinflammatory
      responses, and prevented neurodegeneration without loss of immunogenicity.
      Although the onset of encephalitis was delayed, a small number of suckling mice
      still succumbed to lethal intracerebral infection with the miRNA-targeted
      viruses. Sequence analysis of brain isolates from moribund mice revealed that the
      viruses escaped from miRNA-mediated suppression exclusively through the deletion
      of miRNA targets and viral genome sequence located between the two miRNA targets
      separated by the greatest distance. These findings offer a general strategy to
      control the reversion of virus to a virulent phenotype: a simultaneous miRNA
      targeting of the viral genome at many different functionally important regions
      could prevent virus escape from miRNA-based attenuation, since a deletion of the
      targeted genomic sequences located between the inserted miRNA binding sites would
      be lethal for the virus.

PMID- 22419813
TI  - Abortive replication of influenza virus in mouse dendritic cells.
AB  - The interaction between influenza virus and dendritic cells (DCs) remains poorly
      defined and controversial. Here we show that influenza virus replication in mouse
      bone marrow-derived DCs is abortive, despite viral genome transcription and
      replication occurring for each gene segment and viral hemagglutinin and
      nucleoprotein, at least, being produced. Electron microscopy reveals that virus
      assembly, rather than release of virus from the cell surface, is defective.

PMID- 22419814
TI  - Rapid and persistent suppression of feeding behavior induced by sensitization
      training in Aplysia.
AB  - In Aplysia, noxious stimuli induce sensitization of defensive responses. However,
      it remains largely unknown whether such stimuli also alter nondefensive
      behaviors. In this study, we examined the effects of noxious stimuli on feeding.
      Strong electric shocks, capable of inducing sensitization, also led to the
      suppression of feeding. The use of multiple training protocols revealed that the
      time course of the suppression of feeding was analogous to that of sensitization.
      In addition, the suppression of feeding was present only at the time points in
      which sensitization was expressed. These results suggest that, in Aplysia,
      noxious stimuli may produce concurrent changes in neural circuits controlling
      both defensive and nondefensive behaviors.

PMID- 22419815
TI  - NMDA signaling in CA1 mediates selectively the spatial component of episodic
      memory.
AB  - Recent studies focusing on the memory for temporal order have reported that CA1
      plays a critical role in the memory for the sequences of events, in addition to
      its well-described role in spatial navigation. In contrast, CA3 was found to
      principally contribute to the memory for the association of items with spatial or
      contextual information in tasks focusing on spatial memory. Other studies have
      shown that NMDA signaling in the hippocampus is critical to memory performance in
      studies that have investigated spatial and temporal order memory independently.
      However, the role of NMDA signaling separately in CA1 and CA3 in memory that
      combines both spatial and temporal processing demands (episodic memory) has not
      been examined. Here we investigated the effect of the deletion of the NR1 subunit
      of the NMDA receptor in CA1 or CA3 on the spatial and the temporal aspects of
      episodic memory, using a behavioral task that allows for these two aspects of
      memory to be evaluated distinctly within the same task. Under these conditions,
      NMDA signaling in CA1 specifically contributes to the spatial aspect of memory
      function and is not required to support the memory for temporal order of events.

PMID- 22419816
TI  - Myosin-X functions in polarized epithelial cells.
AB  - Myosin-X (Myo10) is an unconventional myosin that localizes to the tips of
      filopodia and has critical functions in filopodia. Although Myo10 has been
      studied primarily in nonpolarized, fibroblast-like cells, Myo10 is expressed in
      vivo in many epithelia-rich tissues, such as kidney. In this study, we
      investigate the localization and functions of Myo10 in polarized epithelial
      cells, using Madin-Darby canine kidney II cells as a model system. Calcium-switch
      experiments demonstrate that, during junction assembly, green fluorescent protein
      Myo10 localizes to lateral membrane cell-cell contacts and to filopodia-like
      structures imaged by total internal reflection fluorescence on the basal surface.
      Knockdown of Myo10 leads to delayed recruitment of E-cadherin and ZO-1 to
      junctions, as well as a delay in tight junction barrier formation, as indicated
      by a delay in the development of peak transepithelial electrical resistance
      (TER). Although Myo10 knockdown cells eventually mature into monolayers with
      normal TER, these monolayers do exhibit increased paracellular permeability to
      fluorescent dextrans. Importantly, knockdown of Myo10 leads to mitotic spindle
      misorientation, and in three-dimensional culture, Myo10 knockdown cysts exhibit
      defects in lumen formation. Together these results reveal that Myo10 functions in
      polarized epithelial cells in junction formation, regulation of paracellular
      permeability, and epithelial morphogenesis.

PMID- 22419817
TI  - The fission yeast septation initiation network (SIN) kinase, Sid2, is required
      for SIN asymmetry and regulates the SIN scaffold, Cdc11.
AB  - The Schizosaccharomyces pombe septation initiation network (SIN) is an Spg1
      GTPase-mediated protein kinase cascade that triggers actomyosin ring
      constriction, septation, and cell division. The SIN is assembled at the spindle
      pole body (SPB) on the scaffold proteins Cdc11 and Sid4, with Cdc11 binding
      directly to SIN signaling components. Proficient SIN activity requires the
      asymmetric distribution of its signaling components to one of the two SPBs during
      anaphase, and Cdc11 hyperphosphorylation correlates with proficient SIN activity.
      In this paper, we show that the last protein kinase in the signaling cascade,
      Sid2, feeds back to phosphorylate Cdc11 during mitosis. The characterization of
      Cdc11 phosphomutants provides evidence that Sid2-mediated Cdc11 phosphorylation
      promotes the association of the SIN kinase, Cdc7, with the SPB and maximum SIN
      signaling during anaphase. We also show that Sid2 is crucial for the
      establishment of SIN asymmetry, indicating a positive-feedback loop is an
      important element of the SIN.

PMID- 22419819
TI  - Biogenesis of the preprotein translocase of the outer mitochondrial membrane:
      protein kinase A phosphorylates the precursor of Tom40 and impairs its import.
AB  - The preprotein translocase of the outer mitochondrial membrane (TOM) functions as
      the main entry gate for the import of nuclear-encoded proteins into mitochondria.
      The major subunits of the TOM complex are the three receptors Tom20, Tom22, and
      Tom70 and the central channel-forming protein Tom40. Cytosolic kinases have been
      shown to regulate the biogenesis and activity of the Tom receptors. Casein kinase
      2 stimulates the biogenesis of Tom22 and Tom20, whereas protein kinase A (PKA)
      impairs the receptor function of Tom70. Here we report that PKA exerts an
      inhibitory effect on the biogenesis of the beta-barrel protein Tom40. Tom40 is
      synthesized as precursor on cytosolic ribosomes and subsequently imported into
      mitochondria. We show that PKA phosphorylates the precursor of Tom40. The
      phosphorylated Tom40 precursor is impaired in import into mitochondria, whereas
      the nonphosphorylated precursor is efficiently imported. We conclude that PKA
      plays a dual role in the regulation of the TOM complex. Phosphorylation by PKA
      not only impairs the receptor activity of Tom70, but it also inhibits the
      biogenesis of the channel protein Tom40.

PMID- 22419820
TI  - Identification of a novel ADAMTS9/GON-1 function for protein transport from the
      ER to the Golgi.
AB  - A disintegrin-like and metalloprotease with thrombospondin type I motif (ADAMTS9)
      is a member of the secreted metalloprotease family that is believed to digest
      extracellular matrix (ECM) proteins outside of cells. Its Caenorhabditis elegans
      orthologue, GON-1, is involved in ECM degradation and is required for gonad
      morphogenesis. ADAMTS9 and GON-1 have similar domain structures, and both have a
      unique C-terminal domain called the "GON domain," whose function remains unknown.
      Here we show that down-regulation of human ADAMTS9 and C. elegans GON-1 results
      in the inhibition of protein transport from the endoplasmic reticulum (ER) to the
      Golgi. This phenotype was rescued by the expression of the GON domain localizing
      in the ER in human cells and C. elegans. We propose a novel function of ADAMTS9
      and GON-1 in the ER that promotes protein transport from the ER to the Golgi.
      This function is GON-domain dependent but protease activity independent.

PMID- 22419818
TI  - Perispeckles are major assembly sites for the exon junction core complex.
AB  - The exon junction complex (EJC) is loaded onto mRNAs as a consequence of splicing
      and regulates multiple posttranscriptional events. MLN51, Magoh, Y14, and eIF4A3
      form a highly stable EJC core, but where this tetrameric complex is assembled in
      the cell remains unclear. Here we show that EJC factors are enriched in domains
      that we term perispeckles and are visible as doughnuts around nuclear speckles.
      Fluorescence resonance energy transfer analyses and EJC assembly mutants show
      that perispeckles do not store free subunits, but instead are enriched for
      assembled cores. At the ultrastructural level, perispeckles are distinct from
      interchromatin granule clusters that may function as storage sites for splicing
      factors and intermingle with perichromatin fibrils, where nascent RNAs and active
      RNA Pol II are present. These results support a model in which perispeckles are
      major assembly sites for the tetrameric EJC core. This subnuclear territory thus
      represents an intermediate region important for mRNA maturation, between
      transcription sites and splicing factor reservoirs and assembly sites.

PMID- 22419821
TI  - Identification of IGPR-1 as a novel adhesion molecule involved in angiogenesis.
AB  - Angiogenesis-the growth of new blood vessels from preexisting vessels-is an
      important physiological process and is considered to play a key role in tumor
      growth and metastasis. We identified the immunoglobulin-containing and proline
      rich receptor-1 (IGPR-1, also called TMIGD2) gene as a novel cell adhesion
      receptor that is expressed in various human organs and tissues, mainly in cells
      with epithelium and endothelium origins. IGPR-1 regulates cellular morphology,
      homophilic cell aggregation, and cell-cell interaction. IGPR-1 activity also
      modulates actin stress fiber formation and focal adhesion and reduces cell
      migration. Silencing of expression of IGPR-1 by small interfering RNA (siRNA) and
      by ectopic overexpression in endothelial cells showed that IGPR-1 regulates
      capillary tube formation in vitro, and B16F melanoma cells engineered to express
      IGPR-1 displayed extensive angiogenesis in the mouse Matrigel angiogenesis model.
      Moreover, IGPR-1, through its proline-rich cytoplasmic domain, associates with
      multiple Src homology 3 (SH3)-containing signaling proteins, including SH3
      protein interacting with Nck (SPIN90/WISH), bullous pemphigoid antigen-1, and
      calcium channel beta2. Silencing of expression of SPIN90/WISH by siRNA in
      endothelial cells showed that SPIN90/WISH is required for capillary tube
      formation. These features of IGPR-1 suggest that IGPR-1 is a novel receptor that
      plays an important role in cell-cell interaction, cell migration, and
      angiogenesis.

PMID- 22419822
TI  - Comparative transcriptomic analysis of salt adaptation in roots of contrasting
      Medicago truncatula genotypes.
AB  - Evolutionary diversity can be driven by the interaction of plants with different
      environments. Molecular bases involved in ecological adaptations to abiotic
      constraints can be explored using genomic tools. Legumes are major crops
      worldwide and soil salinity is a main stress affecting yield in these plants. We
      analyzed in the Medicago truncatula legume the root transcriptome of two
      genotypes having contrasting responses to salt stress: TN1.11, sampled in a salty
      Tunisian soil, and the reference Jemalong A17 genotype. TN1.11 plants show
      increased root growth under salt stress as well as a differential accumulation of
      sodium ions when compared to A17. Transcriptomic analysis revealed specific gene
      clusters preferentially regulated by salt in root apices of TN1.11, notably those
      related to the auxin pathway and to changes in histone variant isoforms. Many
      genes encoding transcription factors (TFs) were also differentially regulated
      between the two genotypes in response to salt. Among those selected for
      functional studies, overexpression in roots of the A17 genotype of the bHLH-type
      TF most differentially regulated between genotypes improved significantly root
      growth under salt stress. Despite the global complexity of the differential
      transcriptional responses, we propose that an increase in this bHLH TF expression
      may be linked to the adaptation of M. truncatula to saline soil environments.

PMID- 22419823
TI  - Solid-state NMR spectroscopic study of chromophore-protein interactions in the Pr
      ground state of plant phytochrome A.
AB  - Despite extensive study, the molecular structure of the chromophore-binding
      pocket of phytochrome A (phyA), the principal photoreceptor controlling
      photomorphogenesis in plants, has not yet been successfully resolved. Here, we
      report a series of two-dimensional (2-D) magic-angle spinning solid-state NMR
      experiments on the recombinant N-terminal, 65-kDa PAS-GAF-PHY light-sensing
      module of phytochrome A3 from oat (Avena sativa), assembled with uniformly 13C-
      and 15N-labeled phycocyanobilin (u-[13C,15N]-PCB-As.phyA3). The Pr state of this
      protein was studied regarding the electronic structure of the chromophore and its
      interactions with the proximal amino acids. Using 2-D 13C-13C and 1H-15N
      experiments, a complete set of 13C and 15N assignments for the chromophore were
      obtained. Also, a large number of 1H-13C distance restraints between the
      chromophore and its binding pocket were revealed by interfacial heteronuclear
      correlation spectroscopy. 13C doublings of the chromophore A-ring region and the
      C-ring carboxylate moiety, together with the observation of two Pr isoforms, Pr-I
      and Pr-II, demonstrate the local mobility of the chromophore and the plasticity
      of its protein environment. It appears that the interactions and dynamics in the
      binding pocket of phyA in the Pr state are remarkably similar to those of
      cyanobacterial phytochrome (Cph1). The N-terminus of the region modeled (residues
      56-66 of phyA) is highly mobile. Differences in the regulatory processes involved
      in plant and Cph1 phytochromes are discussed.

PMID- 22419824
TI  - Molecular cloning, characterization and analysis of the intracellular
      localization of a water-soluble Chl-binding protein from Brussels sprouts
      (Brassica oleracea var. gemmifera).
AB  - A water-soluble Chl-binding protein from Brussels sprouts (Brassica oleracea var.
      gemmifera), hereafter termed BoWSCP, is categorized into the Class II WSCPs (non
      photoconvertible WSCPs). Previous studies on BoWSCP have focused mainly on its
      biochemical characterization. In this study, we cloned the cDNA encoding BoWSCP.
      Sequence analysis revealed that the BoWSCP gene was composed of a single exon
      corresponding to 654 bp of an open reading frame encoding 218 amino acid
      residues, including 19 residues of a deduced signal peptide targeted to the
      endoplasmic reticulum (ER). Matrix-assisted laser desorption ionization time-of
      flight mass spectrometry analysis of native BoWSCP revealed that the molecular
      mass of the subunit was 19,008.523 Da, corresponding to a mature protein of 178
      amino acids, indicating the removal of 21 residues in the C-terminal region.
      Functional BoWSCP was expressed in Escherichia coli as a hexa-histidine fusion
      protein (BoWSCP-His). When BoWSCP-His was mixed with thylakoid membranes in
      aqueous solution, BoWSCP-His was able to remove Chls from the thylakoid
      membranes. The absorption spectrum of the reconstituted BoWSCP-His was identical
      to that of the native BoWSCP. Chl binding analyses of BoWSCP-His revealed that
      the BoWSCP-His bound both Chl a and Chl b with almost the same affinity in 40%
      methanol solution, although the native BoWSCP had a higher content of Chl a. To
      reveal the intracellular localization of BoWSCP, we constructed a transgenic
      plant expressing the fluorescent protein fused with the N-terminal deduced signal
      peptide of BoWSCP. The fluorescence emitted from the chimeric protein was
      detected in the ER body, an ER-derived compartment observed only in Brassicaceae
      plants.

PMID- 22419825
TI  - Efficacy of microarray profiling data combined with QTL mapping for the
      identification of a QTL gene controlling the initial growth rate in rice.
AB  - Seedling vigor, which is controlled by many quantitative trait loci (QTLs), is
      one of several important agronomic traits for direct-seedling rice systems.
      However, isolating these QTL genes is laborious and expensive. Here, we combined
      QTL mapping and microarray profiling to identify QTL genes for seedling vigor. By
      performing QTL mapping using 82 backcross inbred lines (BILs) of the Koshihikari
      (japonica) and Habataki (indica) cultivars for the rice initial growth, we
      identified two QTLs, early-stage plant development1/2 (qEPD1 and qEPD2), whose
      Koshihikari alleles promote plant height and/or leaf sheath length. Phenotypic
      analysis of the two substituted lines carrying the Habataki qEPD1 or qEPD2 allele
      revealed that qEPD2 functioned more dominantly for the initial growth of rice.
      From the microarray experiment, 55 and 45 candidate genes were found in the qEPD1
      and qEPD2 genomic regions, which are expressed differentially between each
      substitution line (SL) and Koshihikari. Gibberellin 20 oxidase-2 (OsGA20ox2),
      which is identical to Semi Dwarf1 (SD1), was included among the 55 candidate
      genes of qEPD1, whereas its paralog, OsGA20ox1, was included among the 45
      candidate genes of qEPD2. Consistently, introduction of the Koshihikari OsGA20ox1
      allele into SL(qEPD2) increaseed its plant height and leaf sheath length
      significantly relative to the introduction of the Habataki OsGA20ox1 allele.
      Therefore, microarray profiling could be useful for rapidly screening QTL
      candidate genes. We concluded that OsGA20ox1 and OsGA20ox2 (SD1) function during
      the initial growth of rice, but OsGA20ox1 plays a dominant role in increasing
      plant height and leaf sheath length at the initial growth stage.

PMID- 22419826
TI  - The Arabidopsis microRNA396-GRF1/GRF3 regulatory module acts as a developmental
      regulator in the reprogramming of root cells during cyst nematode infection.
AB  - The syncytium is a unique plant root organ whose differentiation is induced by
      plant-parasitic cyst nematodes to create a source of nourishment. Syncytium
      formation involves the redifferentiation and fusion of hundreds of root cells.
      The underlying regulatory networks that control this unique change of plant cell
      fate are not understood. Here, we report that a strong down-regulation of
      Arabidopsis (Arabidopsis thaliana) microRNA396 (miR396) in cells giving rise to
      the syncytium coincides with the initiation of the syncytial induction/formation
      phase and that specific miR396 up-regulation in the developed syncytium marks the
      beginning of the maintenance phase, when no new cells are incorporated into the
      syncytium. In addition, our results show that miR396 in fact has a role in the
      transition from one phase to the other. Expression modulations of miR396 and its
      Growth-Regulating Factor (GRF) target genes resulted in reduced syncytium size
      and arrested nematode development. Furthermore, genome-wide expression profiling
      revealed that the miR396-GRF regulatory system can alter the expression of 44% of
      the more than 7,000 genes reported to change expression in the Arabidopsis
      syncytium. Thus, miR396 represents a key regulator for the reprogramming of root
      cells. As such, this regulatory unit represents a powerful molecular target for
      the parasitic animal to modulate plant cells and force them into novel
      developmental pathways.

PMID- 22419828
TI  - A salt-bridge controlled by ligand binding modulates the hydrolysis reaction in a
      GH5 endoglucanase.
AB  - Cellulases, distributed in at least 15 families of glycoside hydrolases, will
      play a key role in biomass conversion and renewable energy challenges of the
      future. Cel5B from Clostridium thermocellum is a beta-1,4-endoglucanase and a
      member of family 5 of glycoside hydrolases (GH5) and is characterized by an
      (alpha/beta)(8) barrel structure. In contrast to other retaining enzymes, in
      which the catalytic carboxylate groups (glutamate or aspartate) are positioned ~
      5.5 A apart to facilitate nucleophilic attack on the anomeric carbon of the sugar
      substrate, these two residues in Cel5B are positioned ~ 10 A from each other in
      the unliganded wild-type structure. The structure of the enzyme solved in complex
      with a cleavage product (cellobiose) revealed ligand-induced conformational
      changes in the loop carrying Glu140 (proton donor). The reorientation of Glu140
      in the complex reduces the separation of the catalytic glutamate residues to 4.3
      A. In this study, we took advantage of conventional and steered molecular
      dynamics (MD) simulations along with in silico and in vitro mutagenesis to
      investigate the ligand-induced changes of the enzyme and interactions involved in
      preservation of Cel5B conformations in the presence and absence of substrate. We
      determined that the variation in separation of catalytic glutamates in the
      absence and presence of substrate is due to the different protonation states of
      the proton donor glutamate that is largely governed by conformational changes in
      the beta3alpha3 loop. In the absence of substrate, the conformation of Cel5B is
      preserved by an electrostatic interaction between deprotonated Glu140 and
      protonated His91. The ion pair is interrupted upon the binding of substrate, and
      the positional displacement of the beta3alpha3 loop allows Glu140 to become
      oriented within the active site in a less hydrophilic microenvironment that
      assists in Glu140 protonation.

PMID- 22419827
TI  - Light intensity-dependent modulation of chlorophyll b biosynthesis and
      photosynthesis by overexpression of chlorophyllide a oxygenase in tobacco.
AB  - Chlorophyll b is synthesized by the oxidation of a methyl group on the B ring of
      a tetrapyrrole molecule to a formyl group by chlorophyllide a oxygenase (CAO).
      The full-length CAO from Arabidopsis (Arabidopsis thaliana) was overexpressed in
      tobacco (Nicotiana tabacum) that grows well at light intensities much higher than
      those tolerated by Arabidopsis. This resulted in an increased synthesis of
      glutamate semialdehyde, 5-aminolevulinic acid, magnesium-porphyrins, and
      chlorophylls. Overexpression of CAO resulted in increased chlorophyll b synthesis
      and a decreased chlorophyll a/b ratio in low light-grown as well as high light
      grown tobacco plants; this effect, however, was more pronounced in high light.
      The increased potential of the protochlorophyllide oxidoreductase activity and
      chlorophyll biosynthesis compensated for the usual loss of chlorophylls in high
      light. Increased chlorophyll b synthesis in CAO-overexpressed plants was
      accompanied not only by an increased abundance of light-harvesting chlorophyll
      proteins but also of other proteins of the electron transport chain, which led to
      an increase in the capture of light as well as enhanced (40%-80%) electron
      transport rates of photosystems I and II at both limiting and saturating light
      intensities. Although the quantum yield of carbon dioxide fixation remained
      unchanged, the light-saturated photosynthetic carbon assimilation, starch
      content, and dry matter accumulation increased in CAO-overexpressed plants grown
      in both low- and high-light regimes. These results demonstrate that controlled up
      regulation of chlorophyll b biosynthesis comodulates the expression of several
      thylakoid membrane proteins that increase both the antenna size and the electron
      transport rates and enhance carbon dioxide assimilation, starch content, and dry
      matter accumulation.

PMID- 22419829
TI  - Effects of components of semen extenders on the binding of stallion spermatozoa
      to bovine or equine zonae pellucidae.
AB  - The effects of semen extender components on the ability of stallion sperm to bind
      to the zona pellucida (ZP) and the suitability of using bovine ZP for a ZP
      binding assay for stallion sperm were investigated in a series of experiments. In
      Experiment I, binding of stallion sperm to both bovine and equine ZP was
      significantly increased when a skim milk-based extender (EZM) was used. In
      Experiment II, a threefold increase in sperm binding to ZP was observed when
      sperm were diluted in EZM compared with diluents, which contained no milk (TALP,
      LAC, and EmCare). In Experiment III, centrifuging the sperm through Percoll did
      not increase sperm binding to the ZP but did remove any positive effect of EZM on
      sperm-ZP binding. In Experiment IV, exposure of either sperm or ZP to EZM before
      co-incubation did not increase sperm binding to ZP. In Experiment V, sperm
      diluted in TALP containing skim milk, EZM, or INRA96 bound more efficiently to
      the ZP than sperm diluted in TALP without milk proteins. In Experiment VI, sodium
      caseinate, native phosphocaseinate, and caseinoglycopeptide increased sperm
      binding to the ZP. In conclusion, diluents containing milk or milk proteins
      markedly enhanced the number of sperm bound to both equine and bovine ZP.

PMID- 22419830
TI  - NR5A1 is required for functional maturation of Sertoli cells during postnatal
      development.
AB  - The orphan nuclear receptor steroidogenic factor 1 (NR5A1 (SF-1)) is expressed in
      both Sertoli and Leydig cells in the testes. This study investigates the
      postnatal development of the testes of a gonad-specific Nr5a1 knockout (KO)
      mouse, in which Nr5a1 was specifically inactivated. The KO testes appeared
      histologically normal from postnatal day 0 (P0) until P7. However, disorganized
      germ cells, vacuoles, and giant cells appeared by P14 in the seminiferous tubules
      of KO but not control mice. Expression of NR5A1 and various factors was examined
      by immunohistochemistry (IHC). The number of NR5A1-positive Sertoli cells in the
      KO testes was lower compared with controls at all the developmental stages and
      decreased to nearly undetectable levels by P21. IHC for anti-Mullerian hormone
      and p27, immature and mature Sertoli cell markers, respectively, indicated a
      delay in Sertoli cell maturation in the KO testes. The number of Sertoli cell
      expressing factors involved in Sertoli cell differentiation including WT1, SOX9,
      GATA4, and androgen receptor were lower in the KO testes compared with controls.
      Furthermore, fewer proliferating cell nuclear antigen-positive proliferative germ
      cells were observed, and the number of TUNEL-labeled cells was significantly
      higher in the KO testes compared with controls at P14 and P21, indicating
      impaired spermatogenesis. IHC for CYP11A1 (SCC) indicated the presence of
      steroidogenic Leydig cells in the interstitium of the KO testes at all stages
      examined. These results suggest that NR5A1 is essential for Sertoli cell
      maturation and therefore spermatogenesis, during postnatal testis development.

PMID- 22419832
TI  - Using Ensemble-Based Methods for Directly Estimating Causal Effects: An
      Investigation of Tree-Based G-Computation.

PMID- 22419831
TI  - K(+) efflux through two-pore domain K(+) channels is required for mouse embryonic
      development.
AB  - Numerous studies have suggested that K(+) channels regulate a wide range of
      physiological processes in mammalian cells. However, little is known about the
      specific function of K(+) channels in germ cells. In this study, mouse zygotes
      were cultured in a medium containing K(+) channel blockers to identify the
      functional role of K(+) channels in mouse embryonic development. Voltage
      dependent K(+) channel blockers, such as tetraethylammonium and BaCl(2), had no
      effect on embryonic development to the blastocyst stage, whereas K(2P) channel
      blockers, such as quinine, selective serotonin reuptake inhibitors (fluoxetine,
      paroxetine, and citalopram), gadolinium trichloride, anandamide, ruthenium red,
      and zinc chloride, significantly decreased blastocyst formation (P<0.05). RT-PCR
      data showed that members of the K(2P) channel family, specifically KCNK2, KCNK10,
      KCNK4, KCNK3, and KCNK9, were expressed in mouse oocytes and embryos. In
      addition, their mRNA expression levels, except Kcnk3, were up-regulated by above
      ninefold in morula-stage embryos compared with 2-cell stage embryos (2-cells).
      Immunocytochemical data showed that KCNK2, KCNK10, KCNK4, KCNK3, and KCNK9
      channel proteins were expressed in the membrane of oocytes, 2-cells, and
      blastocysts. Each siRNA injection targeted at Kcnk2, Kcnk10, Kcnk4, Kcnk3, and
      Kcnk9 significantly decreased blastocyst formation by ~38% compared with
      scrambled siRNA injection (P<0.05). The blockade of K(2P) channels acidified the
      intracellular pH and depolarized the membrane potential. These results suggest
      that K(2P) channels could improve mouse embryonic development through the
      modulation of gating by activators.

PMID- 22419833
TI  - A comparison of non-homogeneous Markov regression models with application to
      Alzheimer's disease progression.
AB  - Markov regression models are useful tools for estimating the impact of risk
      factors on rates of transition between multiple disease states. Alzheimer's
      disease (AD) is an example of a multi-state disease process in which great
      interest lies in identifying risk factors for transition. In this context, non
      homogeneous models are required because transition rates change as subjects age.
      In this report we propose a non-homogeneous Markov regression model that allows
      for reversible and recurrent disease states, transitions among multiple states
      between observations, and unequally spaced observation times. We conducted
      simulation studies to demonstrate performance of estimators for covariate effects
      from this model and compare performance with alternative models when the
      underlying non-homogeneous process was correctly specified and under model
      misspecification. In simulation studies, we found that covariate effects were
      biased if non-homogeneity of the disease process was not accounted for. However,
      estimates from non-homogeneous models were robust to misspecification of the form
      of the non-homogeneity. We used our model to estimate risk factors for transition
      to mild cognitive impairment (MCI) and AD in a longitudinal study of subjects
      included in the National Alzheimer's Coordinating Center's Uniform Data Set.
      Using our model, we found that subjects with MCI affecting multiple cognitive
      domains were significantly less likely to revert to normal cognition.

PMID- 22419834
TI  - Thermoregulation of foraging honeybees on flowering plants: seasonal variability
      and influence of radiative heat gain.
AB  - 1. During nectar and pollen foraging in a temperate climate, honeybees are
      exposed to a broad range of ambient temperatures, challenging their
      thermoregulatory ability. The body temperature that the bees exhibit results from
      endothermic heat production, exogenous heat gain from solar radiation, and heat
      loss. In addition to profitability of foraging, season was suggested to have a
      considerable influence on thermoregulation. To assess the relative importance of
      these factors, the thermoregulatory behaviour of foragers on 33 flowering plants
      in dependence on season and environmental factors was investigated.2. The bees
      (Apis mellifera carnica Pollman) were always endothermic. On average, the thorax
      surface temperature (T(th)) was regulated at a high and rather constant level
      over a broad range of ambient temperatures (T(th) = 33.7-35.7 degrees C, T(a) =
      10-27 degrees C). However, at a certain T(a), T(th) showed a strong variation,
      depending on the plants from which the bees were foraging. At warmer conditions
      (T(a) = 27-32 degrees C) the T(th) increased nearly linearly with T(a) to a
      maximal average level of 42.6  degrees C. The thorax temperature excess decreased
      strongly with increasing T(a) (T(th)-T(a) = 21.6 - 3.6 degrees C).3. The bees
      used the heat gain from solar radiation to elevate the temperature excess of
      thorax, head, and abdomen. Seasonal dependance was reflected in a 2.7  degrees C
      higher mean T(th) in the spring than in the summer. An anova revealed that season
      had the greatest effect on T(th), followed by T(a) and radiation.4. It was
      presumed the foragers' motivational status to be the main factor responsible for
      the variation of T(th) between seasons and different plants.

PMID- 22419835
TI  - Designing allosteric modulators for active conformational state of m-glutamate G
      protein coupled receptors.
AB  - G-protein coupled receptors (GPCRs) are found to be attractive drug targets for
      the treatment of various neuronal diseases. Allosteric modulators have their role
      in enhancing or suppressing the effect of glutamate on mGluRs. Structure of
      mGluR1 was generated with the help of Modeller software by considering human B2
      adrenergic GPCR protein as template. Structure of various already known drug
      molecules were used for similarity search in the ZINC database and a large number
      of similar molecules were obtained, than filtering of these molecules were done
      by applying drug features. Molecules were screened by Molegro Virtual Docking
      program and numbers of novel molecules were generated by using LigBuilder
      software. Finally 16 novel drug candidates were selected, which were showing
      better results than the seed molecule and previously known modulators. These
      results will help in designing and synthesis of better drugs against diseases
      like Epilepsy and Parkinson's.

PMID- 22419836
TI  - Functional analysis and structure determination of alkaline protease from
      Aspergillus flavus.
AB  - Proteases are one of the highest value commercial enzymes as they have broad
      applications in food, pharmaceutical, detergent, and dairy industries and serve
      as vital tools in determination of structure of proteins and polypeptides.
      Multiple application of these enzymes stimulated interest to discover them with
      novel properties and considerable advancement of basic research into these
      enzymes. A broad understanding of the active site of the enzyme and of the
      mechanism of its inactivation is essential for delineating its structure-function
      relationship. Primary structure analysis of alkaline protease showed 42% of its
      content to be alpha helix making it stable for three dimensional structure
      modeling. Homology model of alkaline protease has been constructed using the X
      ray structure (3F7O) as a template and swiss model as the workspace. The model
      was validated by ProSA, SAVES, PROCHECK, PROSAII and RMSD. The results showed the
      final refined model is reliable. It has 53% amino acid sequence identity with the
      template, 0.24 A as RMSD and has -7.53 as Z-score, the Ramachandran plot analysis
      showed that conformations for 83.4 % of amino acid residues are within the most
      favored regions and only 0.4% in the disallowed regions.

PMID- 22419837
TI  - An approach to delineate primers for a group of poorly conserved sequences
      incorporating the common motif region.
AB  - Glutathione synthetase (gshB) has previously been reported to confer tolerance to
      acidic soil condition in Rhizobium species. Cloning the gene coding for this
      enzyme necessitates the designing of proper primer sets which in turn depends on
      the identification of high quality sequence similarity in multiple global
      alignments. In this experiment, a group of homologous gene sequences related to
      gshB gene (accession no: gi-86355669:327589-328536) of Rhizobium etli CFN 42,
      were extracted from NCBI nucleotide sequence databases using BLASTN and were
      analyzed for designing degenerate primers. However, the T-coffee multiple global
      alignment results did not show any block of conserved region for the above
      sequence set to design the primers. Therefore, we attempted to identify the
      location of common motif region based on multiple local alignments employing the
      MEME algorithm supported with MAST and Primer3. The results revealed some common
      motif regions that enabled us to design the primer sets for related gshB gene
      sequences. The result will be validated in wet lab.

PMID- 22419838
TI  - Molecular modelling, docking and interaction studies of human-plasmogen and
      salmonella enolase with enolase inhibitors.
AB  - Salmonella enteric serovar Typhi Ty2 is a human specific pathogen and an
      etiological agent for typhoid fever. Most of Salmonella serotypes produce
      glycogen which has a comparatively minor role in virulence and colonization, but
      has a more significant role in survival. Enzymes present in glycolytic pathway of
      bacteria help bacteria to survive by activating other factors inside host.
      Numerous pathogenic bacteria species intervene with the plasminogen system, and
      this plasminogen-enolase association may play a critical role in the virulence of
      S. Typhi by causing direct damage to the host cell extracellular matrix, possibly
      by enzymic degradation of extracellular matrix proteins or other protein
      constituents. In this study, molecular modelling of enolase of Salmonella has
      been accomplished in silico by comparative modelling; we have then analyzed Human
      alpha enolase which is a homodimer and serves on epithelial cells with our model.
      Both Structures were docked by D-tartronate semialdehyde phosphate (TSP) and 3
      aminoenolpyruvate phosphate (AEP) enolase inhibitors. Our study shows that
      salmonella enolase and human enolase have different active sites in their
      structure. This will help in development of new ligands, more suitable for
      inhibiting bacterial survival inside host as vaccines for typhoid fever are not
      fully protective. The study also confirmed that enolase Salmonella and Human
      Plasminogen suggested direct physical interaction between both of them as the
      activation loop of plasminogen residues showed conformational changes similar to
      the tissue type plasminogen activator. Various computational biology tools were
      used for our present study such as Modeller, Molegro Virtual Docker, Grommacs.

PMID- 22419839
TI  - Insight into trichomonas vaginalis genome evolution through metabolic pathways
      comparison.
AB  - Trichomonas vaginalis causes the trichomoniasis, in women and urethritis and
      prostate cancer in men. Its genome draft published by TIGR in 2007 presents many
      unusual genomic and biochemical features like, exceptionally large genome size,
      the presence of hydrogenosome, gene duplication, lateral gene transfer mechanism
      and the presence of miRNA. To understand some of genomic features we have
      performed a comparative analysis of metabolic pathways of the T. vaginalis with
      other 22 significant common organisms. Enzymes from the biochemical pathways of
      T. vaginalis and other selected organisms were retrieved from the KEGG metabolic
      pathway database. The metabolic pathways of T. vaginalis common in other selected
      organisms were identified. Total 101 enzymes present in different metabolic
      pathways of T. vaginalis were found to be orthologous by using BLASTP program
      against the selected organisms. Except two enzymes all identified orthologous
      enzymes were also identified as paralogous enzymes. Seventy-five of identified
      enzymes were also identified as essential for the survival of T. vaginalis, while
      26 as non-essential. The identified essential enzymes also represent as good
      candidate for novel drug targets. Interestingly, some of the identified
      orthologous and paralogous enzymes were found playing significant role in the key
      metabolic activities while others were found playing active role in the process
      of pathogenesis. The N-acetylneuraminate lyase was analyzed as the candidate of
      lateral genes transfer. These findings clearly suggest the active participation
      of lateral gene transfer and gene duplication during evolution of T. vaginalis
      from the enteric to the pathogenic urogenital environment.

PMID- 22419840
TI  - A Computational analysis on Lectin and Histone H1 protein of different pulse
      species as well as comparative study with rice for balanced diet.
AB  - The issue of balanced nutrition is of great concern to human. Meat and fish are
      the best sources of protein. The affordability of these resources for people in
      developing countries is less. Thus, there is an increasing interest in pulses and
      its derivates as an alternative to fish and meat. Lectin and histone H1 are the
      most common proteins in various pulses and our interest is in identifying the
      dominant essential amino acids in them for use as supplements. However, actin and
      lectin are common among Oryza Sativa and cicer arietinum. We describe the amount
      of lectin and histone H1 in cicer arietinum, Lens culinaris and Pisum sativum in
      a comparative manner. cicer arietinum was found to contain more essential amino
      acids than Lens culinaris and Pisum sativum. The secondary structures of lectin
      and histone H1 protein were analyzed to gain functional inferences in these
      species. The comparative study shows the relatively poor presence of the amino
      acid methionine in most pulses. However, Oryza Sativa was found to contain
      sufficient methionine. The study shows that pulses (especially cicer arietinum)
      were a suitable alternative source to meat and fish for Lectin and Histone H1
      balance. Hence, pulses could be suggested with rice for balanced protein diet.

PMID- 22419841
TI  - Towards an efficient computational mining approach to identify EST-SSR markers.
AB  - Microsatellites are the markers of choice due to their high abundance
      reproducibility, degree of polymorphism and co-dominant nature. These are mainly
      used for studying the genetic variability in different species and Marker
      assisted selection. Expressed Sequence Tags (ESTs) serve as the main resource for
      Simple Sequence Repeats (SSRs). The computational approach for detecting SSRs and
      developing SSR markers from EST-SSRs is preferred over the conventional methods
      as it reduces time and cost to a great extent. The available EST sequence
      databases, various web interfaces and standalone tools provide the platform for
      an easy analysis of the EST sequences leading to the development of potential EST
      SSR Markers. This paper is an overview of in silico approach to develop SSR
      Markers from the EST sequence using some of the most efficient tools that are
      available freely for academic purpose.

PMID- 22419842
TI  - GIST: Genomic island suite of tools for predicting genomic islands in genomic
      sequences.
AB  - Genomic Islands (GIs) are genomic regions that are originally from other
      organisms, through a process known as Horizontal Gene Transfer (HGT). Detection
      of GIs plays a significant role in biomedical research since such align genomic
      regions usually contain important features, such as pathogenic genes. We have
      developed a use friendly graphic user interface, Genomic Island Suite of Tools
      (GIST), which is a platform for scientific users to predict GIs. This software
      package includes five commonly used tools, AlienHunter, IslandPath, Colombo SIGI
      HMM, INDeGenIUS and Pai-Ida. It also includes an optimization program EGID that
      ensembles the result of existing tools for more accurate prediction. The tools in
      GIST can be used either separately or sequentially. GIST also includes a
      downloadable feature that facilitates collecting the input genomes automatically
      from the FTP server of the National Center for Biotechnology Information (NCBI).
      GIST was implemented in Java, and was compiled and executed on Linux/Unix
      operating systems. AVAILABILITY: The database is available for free at
      http://www5.esu.edu/cpsc/bioinfo/software/GIST.

PMID- 22419843
TI  - ESMP: A high-throughput computational pipeline for mining SSR markers from ESTs.
AB  - With the advent of high-throughput sequencing technology, sequences from many
      genomes are being deposited to public databases at a brisk rate. Open access to
      large amount of expressed sequence tag (EST) data in the public databases has
      provided a powerful platform for simple sequence repeat (SSR) development in
      species where sequence information is not available. SSRs are markers of choice
      for their high reproducibility, abundant polymorphism and high inter-specific
      transferability. The mining of SSRs from ESTs requires different high-throughput
      computational tools that need to be executed individually which are
      computationally intensive and time consuming. To reduce the time lag and to
      streamline the cumbersome process of SSR mining from ESTs, we have developed a
      user-friendly, web-based EST-SSR pipeline "EST-SSR-MARKER PIPELINE (ESMP)". This
      pipeline integrates EST pre-processing, clustering, assembly and subsequently
      mining of SSRs from assembled EST sequences. The mining of SSRs from ESTs
      provides valuable information on the abundance of SSRs in ESTs and will
      facilitate the development of markers for genetic analysis and related
      applications such as marker-assisted breeding. AVAILABILITY: The database is
      available for free at http://bioinfo.aau.ac.in/ESMP.

PMID- 22419844
TI  - NeMedPlant: a database of therapeutic applications and chemical constituents of
      medicinal plants from north-east region of India.
AB  - The North-East region of India is one of the twelve mega biodiversity region,
      containing many rare and endangered species. A curated database of medicinal and
      aromatic plants from the regions called NeMedPlant is developed. The database
      contains traditional, scientific and medicinal information about plants and their
      active constituents, obtained from scholarly literature and local sources. The
      database is cross-linked with major biochemical databases and analytical tools.
      The integrated database provides resource for investigations into hitherto
      unexplored medicinal plants and serves to speed up the discovery of natural
      productsbased drugs. AVAILABILITY: The database is available for free at
      http://bif.uohyd.ac.in/nemedplant/orhttp://202.41.85.11/nemedplant/

PMID- 22419845
TI  - Molecular regulation of vascular endothelial growth factor expression in the
      retinal pigment epithelium.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) plays an important role in
      homeostasis and diseases of the retinal pigment epithelium (RPE),
      choriocapillaris, and, most notably, age-related macular degeneration (AMD).
      Although much is known about VEGF regulation in pathologies, little is known
      about the control of VEGF expression under normal conditions. VEGF expression has
      been previously shown to be regulated in coordination with cell differentiation
      in the muscle and kidney. We therefore tested the hypothesis that VEGF in the
      adult RPE would similarly be regulated in conjunction with differentiation.
      METHODS: A human retinal pigment epithelium cell line (ARPE-19), a line of
      immortalized human RPE cells, was used for all experiments. RPE cells were
      polarized in culture for 4 weeks on laminin-coated Transwells. Levels of VEGF
      mRNA and protein were determined with real-time PCR and enzyme-linked
      immunosorbent assay, respectively. VEGF-luciferase reporter constructs were used
      to identify regions of the VEGF promoter that control VEGF expression in the RPE.
      Microphthalmia-associated transcription factor (MITF)-Tfe transcription factors
      were blocked using either a pan MITF-Tfe dominant negative or specific small
      interfering RNA (siRNA). RESULTS: VEGF mRNA and protein secretion increased over
      time in the RPE cells cultured on Transwells, with protein secretion occurring in
      a polarized fashion primarily toward the basolateral side. Overexpression of a
      dominant negative that targets the MITF-Tfe family resulted in a 50% reduction in
      VEGF expression. The role of the MITF-Tfe family in VEGF regulation in the RPE
      was corroborated in studies with the VEGF-luciferase reporter constructs, where
      deletion of the distal VEGF promoter region containing putative binding sites for
      the MITF-Tfe family resulted in a 50% reduction in VEGF promoter activity. siRNA
      knockdown of the MITF-Tfe family individually, and in combination, revealed that
      downregulation of Tfe3 resulted in reduced VEGF expression. CONCLUSIONS: Our
      results indicate that Tfe3, in conjunction with other MITF-Tfe members, regulates
      VEGF expression in the RPE and are consistent with the hypothesis that VEGF
      expression in RPE cells is regulated as part of their differentiation.

PMID- 22419846
TI  - A Chinese family with Oguchi's disease due to compound heterozygosity including a
      novel deletion in the arrestin gene.
AB  - PURPOSE: Oguchi's disease is a rare autosomal recessive disease and known to be
      caused by mutations in the rhodopsin kinase (GRK1) gene or the arrestin (SAG)
      gene. SAG contains 16 exons and encodes a protein with 405 amino acids. This
      study was to identify the underlying genetic defects in a non-consanguineous
      Chinese family with Oguchi's disease. METHODS: Ophthalmologic examinations
      including fundus photography and electroretinography (ERG) were performed on all
      family members. All exons of the GRK1 gene and the SAG gene were amplified with
      PCR and directly sequenced. Quantitative real-time PCR (qPCR) was performed to
      screen heterozygous deletions/duplications in the SAG gene. Long-range PCR and
      direct sequencing were further performed to define the breakpoints. RESULTS: The
      patient had characteristic clinical features of Oguchi's disease, including night
      blindness, normal vision fields, typical fundus appearance with the Mizuo
      Nakamura phenomenon, nearly undetectable rod b waves in the scotopic 0.01 ERGs,
      and nearly "negative" scotopic 3.0 ERGs. No mutations were found in the GRK1
      gene. A heterozygous nonsense Arg193stop (R193X) mutation was found in the SAG
      gene in the patient and the unaffected mother. No pathogenic SAG mutations were
      found in the unaffected father. qPCRs showed a heterozygous deletion encompassing
      exon 2 of the SAG gene in the patient and the unaffected father. Long-range PCR
      and direct sequencing verified the deletion and revealed the breakpoints of the
      deletion, skipping a 3,224-bp fragment of the SAG gene. The deletion was not
      detected in 96 unrelated healthy controls. This deletion was predicted to
      eliminate the exon 2 and the AUG initiate codon in the mature SAG mRNA and cause
      no production of the SAG protein or low-level production of a non-functional
      truncated protein lacking 134 amino acids in the NH(2) terminus. CONCLUSIONS:
      Compound heterozygosity of a nonsense R193X mutation and a heterozygous deletion
      of 3,224 bp encompassing exon 2 in the SAG gene is the cause of Oguchi's disease
      in this Chinese family. qPCR analysis should be performed if there is a negative
      result of the mutation screening of the SAG gene in patients with Oguchi's
      disease.

PMID- 22419847
TI  - MicroRNA-34b/c suppresses uveal melanoma cell proliferation and migration through
      multiple targets.
AB  - PURPOSE: MicroRNAs (miRNAs) are endogenously expressed, small noncoding RNAs that
      inhibit gene expression by binding to target mRNAs. Recent studies have revealed
      that miRNAs function as tumor suppressors or oncogenes. In the present study, we
      investigated the role of miRNA-34b/c in uveal melanoma. METHODS: Real-time
      reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect
      the expression level of miR-34b/c in uveal melanoma cells and primary samples.
      Subsequently, uveal melanoma cell proliferation was examined by the MTS (3-[4,5
      dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl] -2H
      tetrazolium, inner salt) assay, clone formation assay, and flow cytometry. Cell
      apoptosis was measured by caspase3/7 assay. Cell migration was evaluated by
      transwell migration assay. The target of miR-34b/c was predicted by
      bioinformatics and validated by luciferase assay. In addition, the effect of miR
      34b/c on c-Met, cell cycle-related proteins, v-akt murine thymoma viral oncogene
      homolog (Akt) and extracellular signal-regulated kinase (ERK) pathway was
      determined by western blotting. RESULTS: miR-34b/c expression, which was
      dramatically decreased in uveal melanoma cells and clinical samples, can be
      upregulated by doxorubicin and epigenetic drugs. The transfection of miR-34b/c
      into uveal melanoma cells leads to a significant reduction in cell growth and
      migration. miR-34b/c caused cell cycle G(1) arrest rather than the induction of
      apoptosis. Met proto-oncogene (c-Met) was identified as a target of miR-34b/c in
      uveal melanoma cells. Furthermore, miR-34b/c was confirmed to downregulate the
      expression of c-Met, p-Akt, and cell cycle-related proteins by western blotting.
      CONCLUSIONS: Our results demonstrate that both miR-34b and miR-34c act as tumor
      suppressors in uveal melanoma cell proliferation and migration through the
      downregulation of multiple targets.

PMID- 22419849
TI  - Inflammatory cytokines in aqueous humor of patients with choroidal
      neovascularization.
AB  - OBJECTIVE: To investigate the correlations between aqueous concentrations of
      interleukin 1beta, 6, 8, 10, 12p (IL-1beta, IL-6, IL-8, IL-10, IL-12p), and tumor
      necrosis factor alpha (TNF-alpha) and the parameters of macular edema acquired by
      optical coherence tomography (OCT) in patients with choroidal neovascularization.
      METHODS: IL-1beta, IL-6, IL-8, IL-10, IL-12p, and TNF-alpha in the aqueous humor
      samples of 17 patients with exudative age-related macular degeneration (AMD), ten
      patients with pathological myopia (PM), seven patients with idiopathic choroidal
      neovascularization (CNV), and 14 patients with cataract and idiopathic epiretinal
      membrane or macular hole in the control group were measured with cytometric bead
      array. The maximum macular thickness and macular volume within 1 mm, 3 mm, and 6
      mm were measured with OCT. RESULTS: In the CNV groups, the aqueous levels of IL-6
      and IL-8 were significantly associated with macular volume within 6 mm (p=0.011,
      p=0.008, respectively), while IL-1beta, IL-10, IL-12p, and TNF-alpha showed no
      significant correlation with either the maximum macular thickness or the macular
      volume. By further selecting patients with CNV who had accepted their last
      intravitreal injection of bevacizumab within 3 months, the level of IL-6 still
      significantly correlated with the maximum macular thickness (p=0.019) and macular
      volume within 1 mm (p=0.018), 3 mm (p=0.018), and 6 mm (p=0.022). In patients
      with exudative AMD, the level of IL-6 was significantly associated with the
      maximum macular thickness (p=0.025) and macular volume within 1 mm (p=0.025), 3
      mm (p=0.006), and 6 mm (p=0.002). The aqueous level of all cytokines did not vary
      significantly between the CNV patients who had accepted their last intravitreal
      injection of bevacizumab within 3 months and the other patients, nor was a
      difference found among patients with exudative AMD, PM, and idiopathic CNV, and
      the control group. CONCLUSIONS: Intraocular concentrations of IL-6 and IL-8
      (particularly IL-6) are significantly associated with the volume of macular edema
      in patients with CNV. However, intravitreal injection of antivascular endothelial
      growth factor drugs did not change the intraocular level of these inflammation
      cytokines.

PMID- 22419848
TI  - Potential of human umbilical cord blood mesenchymal stem cells to heal damaged
      corneal endothelium.
AB  - PURPOSE: To test the feasibility of altering the phenotype of umbilical cord
      blood mesenchymal stem cells (UCB MSCs) toward that of human corneal endothelial
      cells (HCEC) and to determine whether UCB MSCs can "home" to sites of corneal
      endothelial cell injury using an ex vivo corneal wound model. METHODS: RNA was
      isolated and purified from UCB MSCs and HCECs. Baseline information regarding the
      relative gene expression of UCB MSCs and HCEC was obtained by microarray
      analysis. Quantitative real-time PCR (q-PCR) verified the microarray findings for
      a subset of genes. The ability of different culture media to direct UCB MSCs
      toward a more HCEC-like phenotype was tested in both tissue culture and ex vivo
      corneal endothelial wound models using three different media: MSC basal medium
      (MSCBM), a basal medium used to culture lens epithelial cells (LECBM), or lens
      epithelial cell-conditioned medium (LECCM). Morphology of the MSCs was observed
      by phase-contrast microscopy or by light microscopic observation of crystal
      violet-stained cells. Immunolocalization of the junction-associated proteins,
      zonula occludins-1 (ZO1) and N-cadherin, was visualized by fluorescence confocal
      microscopy. Formation of cell-cell junctions was tested by treatment with the
      calcium chelator, EGTA. A second microarray analysis compared gene expression
      between UCB MSCs grown in LECBM and LECCM to identify changes induced by the lens
      epithelial cell-conditioned culture medium. The ability of UCB MSCs to "home" to
      areas of endothelial injury was determined using ZO1 immunolocalization patterns
      in ex vivo corneal endothelial wounds. RESULTS: Baseline microarray analysis
      provided information regarding relative gene expression in UCB MSCs and HCECs.
      MSCs attached to damaged, but not intact, corneal endothelium in ex vivo corneal
      wounds. The morphology of MSCs was consistently altered when cells were grown in
      the presence of LECCM. In tissue culture and in ex vivo corneal wounds, UCB MSC
      treated with LECCM were elongated and formed parallel sheets of closely apposed
      cells. In both tissue culture and ex vivo corneal endothelial wounds, ZO1 and N
      cadherin localized mainly to the cytoplasm of UCB MSCs in the presence of MSCBM.
      However, both proteins localized to cell borders when UCB MSCs were grown in
      either LECBM or LECCM. This localization was lost when extracellular calcium
      levels were reduced by treatment with EGTA. A second microarray analysis showed
      that, when UCB MSCs were grown in LECCM instead of LECBM, the relative expression
      of a subset of genes markedly differed, suggestive of a more HCEC-like phenotype.
      CONCLUSIONS: Results indicate that UCB MSCs are able to "home" to areas of
      injured corneal endothelium and that the phenotype of UCB MSCs can be altered
      toward that of HCEC-like cells. Further study is needed to identify the specific
      microenvironmental conditions that would permit tissue engineering of UCB MSCs to
      replace damaged or diseased corneal endothelium.

PMID- 22419850
TI  - Functional characterization of a novel c.614-622del rhodopsin mutation in a
      French pedigree with retinitis pigmentosa.
AB  - PURPOSE: To identify and functionally characterize the mutation responsible for
      autosomal dominant retinitis pigmentosa (adRP) in a large, six-generation French
      family. METHODS: Twenty individuals from this family participated in the genetic
      investigation. Six affected and 14 unaffected individuals from three-generations
      were available for linkage analysis using microsatellite markers flanking the
      rhodopsin (RHO) gene. A two-point logarithm of odds (LOD) score calculation was
      undertaken using GENEMARKER and MLINK software. Sanger sequencing of RHO was
      performed. Cellular localization of the mutant protein was performed by
      transforming SK-N-SH cells with pEGFP-N1-Rho, pEGFP-N1-Rho(P23H), and pEGFP-N1
      Rho(c.614-622del). RESULTS: The proband had nyctalopia, visual field
      constriction, peripheral bone spicule pigmentation of the fundus, central acuity
      (6/24 RE; 6/12 LE) at 55 years of age. Linkage analysis of this family suggested
      RHO as a possible candidate since the flanking marker D3S1292 yielded a LOD score
      of 2.43 at theta=0. Cloning of an exon 3 PCR product and direct sequencing of
      single clones identified a novel deletion in the third exon of RHO, c.614-622del
      (p.Y206-F208del). The deleted mutant protein localized to the endoplasmic
      reticulum and formed inclusion bodies. CONCLUSIONS: This novel deletion in exon 3
      of the RHO gene, c.614-622del results in a classical form of adRP in a multi
      generation French family. Protein expression analyses confirmed that the deletion
      led to protein misfolding and suggest this is a class II mutation, similar to
      P23H, the most common class II mutation seen in North America.

PMID- 22419851
TI  - Stem cell marker CD271 is expressed by vasculogenic mimicry-forming uveal
      melanoma cells in three-dimensional cultures.
AB  - PURPOSE: Cancer stem cells have increased resistance against a variety of anti
      tumor treatment modalities. Vasculogenic mimicry (VM) patterns are present in
      numerous malignant tumor types, represent the formation of perfusion pathways by
      tumor cells, and their presence in tumors is associated with adverse outcome.
      Earlier we have shown that VM-forming tumor cells in three-dimensional (3D) uveal
      melanoma cultures have increased resistance against cytotoxic agents and
      oncolytic herpes simplex virus-mediated destruction. The purpose of the current
      study was to explore the possibility that this increased resistance of VM-forming
      tumor cells is due to a cancer stem cell phenotype. METHODS: The expression of
      cancer stem cell marker cluster of differentiation 271 (CD271) was determined in
      traditional two-dimensional (2D) and 3D cultures of C918 uveal melanoma cells by
      fluorescent immunocytochemistry. RESULTS: We found that the VM-forming tumor cell
      subpopulation in 3D cultures expressed CD271. In contrast, cells grown in 2D
      cultures and tumor cell subpopulations not participating in VM formation in 3D
      cultures were negative for CD271. CONCLUSIONS: These findings suggest that VM
      forming uveal melanoma cells acquire a cancer stem cell-like phenotype that may
      play a role in the increased therapy resistance of these cells.

PMID- 22419854
TI  - Differences in corneal phenotypes between destrin mutants are due to allelic
      difference and modified by genetic background.
AB  - PURPOSE: Mutations in destrin (Dstn) cause corneal abnormalities in mice. A null
      mutation, Dstn(corn1), results in corneal epithelial hyperproliferation,
      inflammation, and neovascularization in the A.BY background (A.BY Dstn(corn1)).
      Homozygosity for a point mutation, Dstn(corn1-2J), results in mild thickening of
      the corneal epithelium but no corneal neovascularization in a C57BL/6 (B6)
      background (B6 Dstn(corn1-2J)). The goal of this study was to determine whether
      phenotypic differences are due to allelic differences between Dstn(corn1) and
      Dstn(corn1-2J), or are the result of genetic background effects. METHODS: We
      generated two congenic (Cg) mouse lines, B6.Cg-Dstn(corn1) and A.BY.Cg-Dstn(corn1
      2J), to compare to the original A.BY Dstn(corn1) and B6 Dstn(corn1-2J) lines. We
      performed immunohistochemistry to assay F-actin accumulation, neovascularization,
      proliferation, and inflammation. By western blot analysis we tested the
      expression of serum response factor (SRF), a known regulator of the Dstn(corn1)
      phenotype. RESULTS: The Dstn(corn1) mutation leads to neovascularization,
      hyperproliferation, and inflammation in the cornea of A.BY Dstn(corn1) as well as
      B6.Cg-Dstn(corn1) mice. We did not observe significant corneal neovascularization
      or hyperproliferation in either A.BY.Cg-Dstn(corn1-2J) or B6 Dstn(corn1-2J) mice.
      Actin accumulation, neovascularization, epithelial proliferation and inflammation
      in B6.Cg-Dstn(corn1) cornea are significantly reduced when compared to A.BY
      Dstn(corn1)cornea. SRF changes are consistent in Dstn(corn1) mutants, regardless
      of genetic background. CONCLUSIONS: Differences in the abnormal phenotypes of
      Dstn mutants result from allelic differences between Dstn(corn1) and Dstn(corn1
      2J) . Moreover, phenotypes of Dstn(corn1) mice are modified by genetic
      background, suggesting the existence of genetic modifiers. Protein analysis
      suggests that a genetic modifier affects phenotypic severity functionally
      downstream from or in a pathway independent from SRF. These data demonstrate that
      natural genetic variation affects phenotypic severity in Dstn(corn1) mice.

PMID- 22419852
TI  - Blockade of vascular adhesion protein-1 attenuates choroidal neovascularization.
AB  - PURPOSE: Vascular adhesion protein (VAP)-1 is an adhesion molecule elucidated as
      a mediator of the leukocyte recruitment cascade. The purpose of this study was to
      investigate the role of VAP-1 in ocular inflammatory neovascularization using a
      mouse laser-induced choroidal neovascularization (CNV) model. METHODS: CNV was
      induced with 532 nm laser irradiation in C57BL/6 mice, and production of VAP-1
      protein in the retinal pigment epithelium (RPE) choroid during CNV formation was
      examined. CNV animals were treated with the specific VAP-1 inhibitor U-V002 or
      vehicle solution, and the volume of CNV tissue was evaluated with volumetric
      measurements. Macrophage infiltration into the CNV lesions was evaluated using
      two different techniques, flatmount staining and real-time polymerase chain
      reaction (PCR) for F4/80. The protein levels of intercellular adhesion molecule
      (ICAM)-1, monocyte chemoattractant protein (MCP)-1, P-selectin, and vascular
      endothelial growth factor (VEGF) in the RPE-choroid were measured with enzyme
      linked immunosorbent assay (ELISA). RESULTS: VAP-1 inhibition significantly
      suppressed CNV formation in a dose-dependent manner and reduced macrophage
      infiltration into CNV lesions. Furthermore, VAP-1 blockade decreased the
      expression of ICAM-1 and MCP-1, both of which play a pivotal role in macrophage
      recruitment. CONCLUSIONS: Our data suggest VAP-1 has an important role during
      ocular inflammatory neovascularization through leukocyte recruitment. VAP-1
      inhibition may be a novel and potent therapeutic strategy in treating CNV
      formation.

PMID- 22419853
TI  - KLF6SV1 siRNA inhibits proliferation of human lens epithelial cells.
AB  - PURPOSE: To investigate whether transfection with Kruppel-like factor 6 splice
      variant 1 (KLF6SV1) siRNA can inhibit proliferation of human lens epithelial cell
      (HLEC). METHODS: Plasmid containing KLF6SV1 siRNA was used to decrease the level
      of KLF6SV1 protein in HLEC. The expression of protein27 kinase inhibition protein
      1 (p27(kip1)) and proliferation cell nuclear antigen (PCNA) was tested with
      western blot. Cell proliferation was assayed by 3-(4,5-dimethylthiazolyl-2-)-2,5
      diphenyltetrazoliumbromide (MTT) assay and bromodeoxyuridine (BrdU)
      incorporation. RESULTS: KLF6SV1 siRNA can decrease KLF6SV1 expression which leads
      to increased levels of p27(kip1) and decreased expression of PCNA in HLEC. Cells
      transfected with pKLF6SV1 siRNA showed less viability compared with the control
      group in vitro. CONCLUSIONS: KLF6SV1 siRNA can effectively inhibit HLEC
      proliferation. It can be regarded as a novel target to treat posterior capsular
      opacity (PCO).

PMID- 22419855
TI  - Bilateral visual loss due to a giant olfactory meningioma.
AB  - Olfactory groove meningiomas can present as large and insidious masses in the
      anterior cranial base. Due to their location and minimal clinical symptoms, these
      tumors can go undetected until they have grown extremely large. We present a
      clinical case and discuss the surgical management of a 63-year-old man who
      presented for an initial eye examination with bilateral visual loss for over 2
      years due to a giant olfactory meningioma encompassing his entire frontal lobe
      and compressing on his optic nerves.

PMID- 22419856
TI  - Insight into 144 patients with ocular vascular events during VEGF antagonist
      injections.
AB  - AIM: To record ocular vascular events following injections of vascular
      endothelium growth factor (VEGF) antagonists. METHODS: Collaborative multicenter
      case series (48 cases), literature reviews (32 cases), and reports to the FDA (64
      cases) of patients that had vascular occlusions during anti-VEGF therapy were
      collected and analyzed. RESULTS: A total of 144 cases of ocular vascular events
      were identified, with these diagnosed a median of 15 days after anti-VEGF
      injection. The majority of patients had pre-existing risk factors for
      cardiovascular events and nine patients had a prior history of glaucoma. Mean
      visual acuity dropped by 6.4 lines with severe visual loss after injection to NLP
      (five eyes), LP (six eyes), and HM (two eyes). The overall risk of ocular
      vascular events following a VEGF antagonist injection was 0.108% in the general
      population and 2.61% in the diabetic population. Mean retinal arterial
      constriction after intravitreal bevacizumab in 13 eyes was 21% (standard
      deviation = 27%), and mean retinal venous constriction was 8% (standard deviation
      = 30%). CONCLUSION: Ocular vascular events are rare during anti-VEGF therapy, but
      can lead to severe visual loss and may be caused by a number of factors including
      the vasoconstrictor effect of the drug, a post-injection rise of intraocular
      pressure, patient stress as a result of the procedure, and the patient's natural
      history of underlying ocular or systemic diseases. The diabetic population
      appears to have a tendency towards ocular vascular occlusions.

PMID- 22419857
TI  - Comparison of the effect between pegaptanib and ranibizumab on exudative age
      related macular degeneration with small lesion size.
AB  - PURPOSE: To compare the effect of pegaptanib versus ranibizumab on exudative age
      related macular degeneration (AMD) with small lesion size. METHODS: This is a
      retrospective study of 81 eyes from 78 patients with exudative AMD treated and
      followed up over 12 months. Patients with baseline best corrected visual acuity
      (BCVA) under 20/400 and with a greatest linear dimension of lesion over 4500 MUm
      were excluded from the study. Twenty-six eyes from 25 patients were treated with
      three consecutive intravitreal injections of pegaptanib (IVP group) and 55 eyes
      from 54 patients were treated with three consecutive ranibizumab injections (IVR
      group). Each therapy was repeated as needed. The alteration in BCVA was evaluated
      in the IVP and IVR groups. RESULTS: No differences were detected in baseline
      parameters between the IVP and IVR groups. The mean BCVA (logMAR) at month 1, 3,
      6 and 12 after the initial treatment was improved from baseline in the IVP group
      (-0.095, -0.17, -0.18 and -0.18, respectively) and in the IVR group (-0.077, 
      0.15, -0.17 and -0.11, respectively), which was statistically significant. There
      was no difference in the change in mean BCVA between IVP and IVR groups at the
      same time periods. CONCLUSIONS: The visual outcome of IVP was equivalent with IVR
      in exudative AMD with small lesion size.

PMID- 22419858
TI  - Comparison of the latanoprost 0.005%/timolol 0.5% + brinzolamide 1% versus
      dorzolamide 1%/timolol 0.5% + latanoprost 0.005%: a 12-week, randomized open
      label trial.
AB  - OBJECTIVE: To compare the safety and effectiveness of fixed-combination regimes
      (latanoprost- timolol and brinzolamide 1% compared to dorzolamide 1%/timolol and
      latanoprost) in open-angle glaucoma patients after switching from a combination
      of three topical antiglaucoma eye drops. METHODS: We conducted an open,
      randomized 12-week multicenter prospective study. We randomly allocated 39
      patients who had been treated with three antiglaucoma eye drops (prostaglandin
      F(2alpha) analogues plus beta-blockers and carbonic anhydrase inhibitors) into
      two groups. Group A (n = 20) were treated with latanoprost-timolol and
      brinzolamide 1% therapy and Group B (n = 16) were treated with dorzolamide
      1%/timolol and latanoprost. Thirty-six patients completed all 12 weeks of this
      study. The major clinical parameters measured were intraocular pressure (IOP),
      conjunctive hyperemia, superficial punctate keratopathy and hyperpigmentation of
      eyelid at baseline, 4, and 12 weeks. Additionally noted were adverse events and
      patient preferences, measured using a questionnaire at study initiation and at 12
      weeks. RESULTS: AT BASELINE, IOPS WERE (GROUP A: 14.1 +/- 2.9 mmHg, B: 14.5 +/-
      2.9 mmHg; P = 0.658), (Group A: 13.8 +/- 2.6 mmHg, B: 14.3 +/- 2.8 mmHg; P =
      0.715) at 4 weeks, and (Group A: 14.1 +/- 2.7 mmHg, B: 14.2 +/- 2.7 mmHg; P =
      0.538) at 12 weeks. Among the groups, there was no significant difference at any
      time point after baseline (P = 0.923, 0.951, respectively). All adverse events
      were not remarkably different after therapy. In regards to patient preference
      before and after switching therapy, 10 patients (50%) in Group A and 10 patients
      (63%) in Group B preferred using fixed-combination eye drop therapy. CONCLUSIONS:
      Effectiveness and safety were maintained in both groups after switching therapy.
      Overall, patients generally preferred using a fixed-combination therapy.

PMID- 22419859
TI  - Local pulmonary administration of factor VIIa (rFVIIa) in diffuse alveolar
      hemorrhage (DAH) - a review of a new treatment paradigm.
AB  - BACKGROUND: Diffuse alveolar hemorrhage (DAH) is a clinical syndrome with typical
      symptoms dyspnea and hemoptysis. DAH is a complication of specific diseases, in
      some cases with acute catastrophic hemoptysis, while other patients present low
      grade alveolar bleeding with a need of chronic transfusion as in pulmonary
      hemosiderosis. METHODS: Current literature in the PubMed database and other
      sources was reviewed in order to evaluate the current treatment recommendations,
      efficacy of this treatment, and finally the risk of complications after off-label
      use of rFVIIa in respect to DAH. OBJECTIVES: (i) To elucidate the clinical
      aspects of alveolar hemorrhage, (ii) to develop a simple diagnostic algorithm in
      order to separate DAH from other important pulmonary diseases with similar
      clinical picture and comparably high mortality. Such an algorithm has important
      therapeutic consequences because these diseases: acute lung injury (ALI), acute
      respiratory distress syndrome (ARDS) and bronchiolitis obliterans organizing
      pneumonia (BOOP) have different therapies, (iii) to evaluate and discuss whether
      local pulmonary administration may improve outcome and reduce mortality in DAH,
      and (iv) to suggest a treatment schedule. RESULTS: Hitherto the diagnosis and
      treatment of DAH has been based on anecdotal reports. The treatment has relied on
      different unspecific treatment modalities based on a mixture of treatment of the
      underlying disease and treatment without evidence targeted to stop the alveolar
      bleeding. However, recently a number of publications have advocated the use of
      intrapulmonary rFVIIa. Even in severe bleeding DAH has been shown to respond
      promptly without thromboembolic complication when FVIIa was administered locally
      via the air side, because the FVIIa does not penetrate the alveolo-capillary
      membrane to the blood-side. The incidence of DAH (in the US and Europe is 100,000
      150,000, and 50,000 patients annually are at risk of developing DAH following
      hematopoietic stem cell transplant (HSCT) and autoimmune diseases. Finally 50,000
      100,000 patients may be falsely categorized as having acute respiratory distress
      syndrome/acute lung injury (ARDS/ALI) because DAH and ARDS cannot be separated
      clinically. A new treatment paradigm of DAH is proposed as no other intervention
      has been able to ensure pulmonary hemostasis in DAH. The diagnosis of DAH is
      simple, a series of broncho-alveolar washes which become increasingly bloody.
      This test should be performed in all patients with pulmonary opacities in order
      to separate ARDS/ALI from DAH. FVIIa administrated via pulmonary route is "drug
      of choice", because it stops bleeding in the life-threatening syndrome DAH.
      Hemostasis is obtained after only one to two small doses of FVIIa (50 MUg/kg body
      weight per dose) and after hemostasis the oxygen transport quickly improves.
      CONCLUSION: Intrapulmonary administration of rFVIIa is recommended as the
      treatment of choice for DAH and blast lung injury (BLI) because the treatment has
      been shown to be successful and uncomplicated in spite of the fact that only a
      small series of DAH has been documented.

PMID- 22419860
TI  - Pharmacokinetics of iron isomaltoside 1000 in patients with inflammatory bowel
      disease.
AB  - BACKGROUND: Iron isomaltoside 1000 is a novel injectable iron compound which
      offers potential advantages in the treatment of subjects with iron-deficiency
      anemia. We studied the pharmacokinetics (PK) of this novel compound in subjects
      with mild-to-moderate inflammatory bowel disease (IBD). METHODS: This open-label,
      crossover, single-center trial was conducted in 12 subjects with IBD who were
      allocated to one of the two single intravenous (IV) bolus sequences of iron
      isomaltoside 1000: 100 mg followed by 200 mg, or vice-versa. PK variables were
      analyzed according to a single-compartment model. RESULTS: The concentration
      versus-time relationship for isomaltoside-bound iron (IBI) and total iron (TI)
      showed first-order kinetics with small deviations from dose-linearity. The area
      under the concentration-time curve (AUC) values in h * MUg/mL for IBI following
      100 mg and 200 mg doses were 888 and 2141 respectively, and for TI following 100
      mg and 200 mg doses, the AUC values were 1010 and 2319 respectively. The
      corresponding maximum serum concentration (C(max)) values in MUg/mL were 35.6 and
      68.6 for IBI, and 37.3 and 71.1 for TI. The half-life (T(1/2)) values for IBI and
      TI were between 20.8-23.5 hours. The apparent volume of distribution (V(D))
      ranged from 3.0-3.5 L. Only approximately 1% of the doses administered were
      excreted in the urine. No serious adverse event (SAE) was reported. One subject
      was withdrawn after the 100 mg dose due to abdominal pain and flushing.
      CONCLUSION: At the administered doses, iron isomaltoside 1000 showed first-order
      PK, and did not raise safety concerns in patients with IBD. The PK parameters for
      IBI were close to those of TI.

PMID- 22419861
TI  - Differences in subjective and objective respiratory parameters in patients with
      chronic obstructive pulmonary disease with and without pain.
AB  - BACKGROUND: Few studies have evaluated the associations between respiratory
      parameters and pain in chronic obstructive pulmonary disease (COPD). The purpose
      of this study is to evaluate the differences in respiratory parameters between
      COPD patients who did and did not have pain. METHODS: In this cross-sectional
      study respiratory parameters were measured by spirometry and the St Georges
      Respiratory Questionnaire. Patients responded to a single question that asked if
      they were generally bothered by pain. RESULTS: Of the 100 patients, 45% reported
      that they were generally bothered by pain. Patients who had pain reported a
      higher number of comorbidities (P < 0.001) and higher breathlessness scores (P =
      0.003). Physical dimensions of breathlessness were significantly associated with
      pain (P <= 0.03). The results of logistic regression analysis determined that a
      higher number of comorbidities (OR = 0.28; P = 0.026) and higher breathlessness
      scores (OR = 1.03; P = 0.003) made significant unique contributions to the
      prediction of pain group membership. CONCLUSIONS: Comorbidity and breathlessness
      were risk factors for pain and the physical dimensions of breathlessness were
      associated with pain.

PMID- 22419862
TI  - Comparative efficacy of indacaterol in chronic obstructive pulmonary disease.
AB  - Long-acting bronchodilators have been shown to improve multiple clinical outcomes
      in chronic obstructive pulmonary disease (COPD) including lung function,
      symptoms, dyspnea, quality of life, and exacerbations. Indacaterol is a novel,
      inhaled, long-acting beta2-agonist providing 24-hour bronchodilation with once
      daily dosing. It is currently approved for the maintenance treatment of COPD to
      be administered as 150 or 300 MUg once-daily doses as licensed in many countries
      and 75 MUg as licensed in the US by means of a single-dose dry powder inhaler.
      The data from clinical development support a favorable safety and tolerability
      profile within the beta2-agonist drug class, with no relevant issues identified.
      Current evidence indicates that indacaterol is suitable for use as first-line
      monotherapy in COPD patients with moderate disease (Global Initiative for Chronic
      Obstructive Lung Disease [GOLD] stage II) and beyond that do not require an
      inhaled corticosteroid (ICS) as per GOLD guidelines, or in combination with an
      ICS in severe or very severe patients with repeated exacerbations. Data from
      trials with the novel once-daily beta2-agonist, indacaterol, indicate superior
      bronchodilation and clinical efficacy over twice-daily long-acting beta2-agonists
      and at least equipotent bronchodilation as once-daily tiotropium. Bronchodilators
      are central in the symptomatic management of COPD. It is likely that once-daily
      dosing of a bronchodilator would be a significant convenience and probably a
      compliance-enhancing advantage, leading to improved overall clinical outcomes in
      patients with COPD.

PMID- 22419863
TI  - Safety and efficacy of dual therapy with GSK233705 and salmeterol versus
      monotherapy with salmeterol, tiotropium, or placebo in a crossover pilot study in
      partially reversible COPD patients.
AB  - BACKGROUND: GSK233705 is an inhaled, long-acting muscarinic antagonist in
      development for the treatment of chronic obstructive pulmonary disease (COPD).
      This study was performed to see if the addition of GSK233705 to salmeterol would
      provide greater bronchodilation than salmeterol or tiotropium alone in COPD.
      METHODS: In an incomplete-block, three-period, crossover design, dually
      responsive patients received three of the following five treatments: GSK233705 20
      MUg plus salmeterol 50 MUg twice-daily; GSK233705 50 MUg plus salmeterol 50 MUg
      twice-daily; salmeterol 50 MUg or placebo, each twice-daily; and tiotropium 18
      MUg or placebo once-daily for 7 days. Each treatment period was separated by a 14
      day washout. The primary efficacy endpoint was morning (trough) forced expiratory
      volume in 1 second (FEV(1)) on Day 8, following 7 days of treatment. Secondary
      endpoints included pulmonary function, plethysmography, pharmacokinetics of
      GSK233705 and salmeterol, adverse events (AEs), electrocardiograms (ECGs), vital
      signs, and laboratory parameters. RESULTS: A total of 47 patients were
      randomized. The mean % predicted normal postbronchodilator FEV(1) was 55% at
      screening. Compared with placebo (n = 24), the adjusted mean change from baseline
      in trough FEV(1) on Day 8 was 215 mL higher with GSK233705 20 MUg + salmeterol (n
      = 23) and 203 mL higher with GSK233705 50 MUg + salmeterol (n = 27), whereas with
      salmeterol (n = 27) and tiotropium (n = 28) the changes were 101 mL and 118 mL
      higher, respectively. The primary efficacy results were supported by the results
      from the other secondary lung function assessments. AEs were reported by similar
      proportions of patients across the treatment groups, with headache the most
      frequently reported treatment-related AE reported by one subject receiving each
      of GSK233705 20 MUg + salmeterol, tiotropium, and placebo. No significant
      differences were seen in vital signs, ECGs, or laboratory parameters between the
      groups. CONCLUSION: The addition of GSK233705 to salmeterol in partially
      reversible COPD patients resulted in greater bronchodilation than salmeterol or
      tiotropium alone and was well tolerated.

PMID- 22419864
TI  - Fibrinogen, chronic obstructive pulmonary disease (COPD) and outcomes in two
      United States cohorts.
AB  - BACKGROUND: Fibrinogen is a marker of systemic inflammation and may be important
      in the pathogenesis and progression of chronic obstructive pulmonary disease
      (COPD). METHODS: We used baseline data from Atherosclerosis Risk in Communities
      and Cardiovascular Health Studies to determine the relation between fibrinogen
      levels and COPD and to examine how fibrinogen levels at baseline affected
      outcomes of death, development of COPD, lung function decline, and COPD
      hospitalizations. RESULTS: Our study sample included 20,192 subjects, of whom
      2995 died during the follow-up period. The mean fibrinogen level was 307.6 mg/dL
      and 10% of the sample had levels >393.0 mg/dL. Subjects with Stage 3 or 4 COPD
      were more likely to have a fibrinogen level >393.0 mg/dL (odds ratio 2.28, 95%
      confidence interval [CI]: 1.79-2.95). In the longitudinal adjusted models,
      fibrinogen levels >393 mg/dL predicted mortality (hazards ratio 1.54, 95% CI:
      1.39-1.70), COPD-related hospitalization (hazards ratio 1.45, 95% CI: 1.27-1.67),
      and incident Stage 2 COPD (odds ratio 1.36, 95% CI: 1.07-1.74). Similar findings
      were seen with continuous fibrinogen levels. CONCLUSION: In the Atherosclerosis
      Risk in Communities/Cardiovascular Health Studies cohort data, higher fibrinogen
      levels are predictors of mortality, COPD-related hospitalizations, and incident
      Stage 2 COPD.

PMID- 22419865
TI  - Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in
      rats.
AB  - PURPOSE: Celastrol, a traditional Chinese medicine, is widely used in anti
      inflammation and anti-angiogenesis research. However, the poor water solubility
      of celastrol restricts its further application. This paper aims to study the
      effect of celastrol nanoparticles (CNPs) on corneal neovascularization (CNV) and
      determine the possible mechanism. METHODS: To improve the hydrophilicity of
      celastrol, celastrol-loaded poly(ethylene glycol)-block-poly(E-caprolactone)
      nanopolymeric micelles were developed. The characterization of CNPs was measured
      by dynamic light scattering and transmission electron microscopy analysis.
      Celastrol loading content and release were assessed by ultraviolet-visible
      analysis and high performance liquid chromatography, respectively. In vitro,
      human umbilical vein endothelial cell proliferation and capillary-like tube
      formation were assayed. In vivo, suture-induced CNV was chosen to evaluate the
      effect of CNPs on CNV in rats. Immunohistochemistry for CD68 assessed the
      macrophage infiltration of the cornea on day 6 after surgery. Real-time
      quantitative reverse transcription-polymerase chain reaction and enzyme-linked
      immunosorbent assay were used to evaluate the messenger ribonucleic acid and
      protein levels, respectively, of vascular endothelial growth factor, matrix
      metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea.
      RESULTS: The mean diameter of CNPs with spherical shape was 48 nm. The celastrol
      loading content was 7.36%. The release behavior of CNPs in buffered solution (pH
      7.4) showed a typical two-phase release profile. CNPs inhibited the proliferation
      of human umbilical vein endothelial cells in a dose-independent manner and
      suppressed the capillary structure formation. After treatment with CNPs, the
      length and area of CNV reduced from 1.16 +/- 0.18 mm to 0.49 +/- 0.12 mm and from
      7.71 +/- 0.94 mm(2) to 2.29 +/- 0.61 mm(2), respectively. Macrophage infiltration
      decreased significantly in the CNP-treated corneas. CNPs reduced the expression
      of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte
      chemoattractant protein 1 in the cornea on day 6 after suturing. CONCLUSION: CNPs
      significantly inhibited suture-induced CNV by suppressing macrophage infiltration
      and the expression of vascular endothelial growth factor and matrix
      metalloproteinase 9 in the rat cornea.

PMID- 22419866
TI  - Antibiofilm surface functionalization of catheters by magnesium fluoride
      nanoparticles.
AB  - The ability of bacteria to colonize catheters is a major cause of infection. In
      the current study, catheters were surface-modified with MgF(2) nanoparticles
      (NPs) using a sonochemical synthesis protocol described previously. The one-step
      synthesis and coating procedure yielded a homogenous MgF(2) NP layer on both the
      inside and outside of the catheter, as analyzed by high resolution scanning
      electron microscopy and energy dispersive spectroscopy. The coating thickness
      varied from approximately 750 nm to 1000 nm on the inner walls and from
      approximately 450 nm to approximately 580 nm for the outer wall. The coating
      consisted of spherical MgF(2) NPs with an average diameter of approximately 25
      nm. These MgF(2) NP-modified catheters were investigated for their ability to
      restrict bacterial biofilm formation. Two bacterial strains most commonly
      associated with catheter infections, Escherichia coli and Staphylococcus aureus,
      were cultured in tryptic soy broth, artificial urine and human plasma on the
      modified catheters. The MgF(2) NP-coated catheters were able to significantly
      reduce bacterial colonization for a period of 1 week compared to the uncoated
      control. Finally, the potential cytotoxicity of MgF(2) NPs was also evaluated
      using human and mammalian cell lines and no significant reduction in the
      mitochondrial metabolism was observed. Taken together, our results indicate that
      the surface modification of catheters with MgF(2) NPs can be effective in
      preventing bacterial colonization and can provide catheters with long-lasting
      self-sterilizing properties.

PMID- 22419867
TI  - Biochemical analysis of Cassia fistula aqueous extract and phytochemically
      synthesized gold nanoparticles as hypoglycemic treatment for diabetes mellitus.
AB  - Cassia fistula stem bark was used for the preparation of aqueous extract and
      synthesis of gold nanoparticles to evaluate the hypoglycemic effects of the
      plant. The synthesized gold nanoparticles were characterized by ultraviolet
      visible spectroscopy for their absorbance pattern, Fourier transform infrared
      spectroscopy to identify possible functional groups, and scanning electron
      microscopy to determine the size of the nanoparticles. The present investigation
      reports the efficacy of the gold nanoparticles as promising in the treatment of
      hyperglycemia. Body weight, serum glucose concentrations, liver function tests,
      kidney function tests, and lipid profile were analyzed. A significantly larger
      decrease in serum biochemistry parameters and an increase in body weight, total
      protein levels, and high-density lipoprotein were observed in rats with
      streptozotocin-induced diabetes treated with gold nanoparticles than in the ones
      treated with the aqueous extract. The results of this study confirm that C.
      fistula gold nanoparticles have promising antidiabetic properties.

PMID- 22419868
TI  - Titanium dioxide induces apoptotic cell death through reactive oxygen species
      mediated Fas upregulation and Bax activation.
AB  - BACKGROUND: Titanium dioxide (TiO(2)) has been widely used in many areas,
      including biomedicine, cosmetics, and environmental engineering. Recently, it has
      become evident that some TiO(2) particles have a considerable cytotoxic effect in
      normal human cells. However, the molecular basis for the cytotoxicity of TiO(2)
      has yet to be defined. METHODS AND RESULTS: In this study, we demonstrated that
      combined treatment with TiO(2) nanoparticles sized less than 100 nm and
      ultraviolet A irradiation induces apoptotic cell death through reactive oxygen
      species-dependent upregulation of Fas and conformational activation of Bax in
      normal human cells. Treatment with P25 TiO(2) nanoparticles with a hydrodynamic
      size distribution centered around 70 nm (TiO(2) (P25-70)) together with
      ultraviolet A irradiation-induced caspase-dependent apoptotic cell death,
      accompanied by transcriptional upregulation of the death receptor, Fas, and
      conformational activation of Bax. In line with these results, knockdown of either
      Fas or Bax with specific siRNA significantly inhibited TiO(2)-induced apoptotic
      cell death. Moreover, inhibition of reactive oxygen species with an antioxidant,
      N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational
      activation of Bax, and subsequent apoptotic cell death in response to combination
      treatment using TiO(2) (P25-70) and ultraviolet A irradiation. CONCLUSION: These
      results indicate that sub-100 nm sized TiO(2) treatment under ultraviolet A
      irradiation induces apoptotic cell death through reactive oxygen species-mediated
      upregulation of the death receptor, Fas, and activation of the preapoptotic
      protein, Bax. Elucidating the molecular mechanisms by which nanosized particles
      induce activation of cell death signaling pathways would be critical for the
      development of prevention strategies to minimize the cytotoxicity of
      nanomaterials.

PMID- 22419869
TI  - Nano-TiO2/PEEK bioactive composite as a bone substitute material: in vitro and in
      vivo studies.
AB  - BACKGROUND: Compared with titanium (Ti) and other metal implant materials,
      poly(ether-ether ketone) (PEEK) shows outstanding biomechanical properties. A
      number of studies have also reported attractive bioactivity for nano-TiO(2) (n
      TiO(2)). METHODS: In this study, n-TiO(2)/PEEK nanocomposites were prepared,
      taking advantage of the unique properties of both PEEK polymer and n-TiO(2). The
      in vitro and in vivo bioactivity of these nanocomposites was assessed against a
      PEEK polymer control. The effect of surface morphology or roughness on the
      bioactivity of the n-TiO(2)/PEEK nanocomposites was also studied. n-TiO(2)/PEEK
      was successfully fabricated and cut into disks for physical and chemical
      characterization and in vitro studies, and prepared as cylindrical implants for
      in vivo studies. Their presence on the surface and dispersion in the composites
      was observed and analyzed by scanning and transmission electron microscopy and X
      ray photoelectron spectroscopy. RESULTS: Bioactivity evaluation of the
      nanocomposites revealed that pseudopods of osteoblasts preferred to anchor at
      areas where n-TiO(2) was present on the surface. In a cell attachment test,
      smooth PEEK showed the lowest optical density value (0.56 +/- 0.07) while rough n
      TiO(2)/PEEK exhibited the highest optical density value (1.21 +/- 0.34, P <
      0.05). In in vivo studies, the percent bone volume value of n-TiO(2)/PEEK was
      approximately twice as large as that of PEEK (P < 0.05). Vivid three-dimensional
      and histologic images of the newly generated bone on the implants further
      supported our test results. CONCLUSION: Our study demonstrates that n-TiO(2)
      significantly improves the bioactivity of PEEK, especially if it has a rough
      composite surface. A n-TiO(2)/PEEK composite with a rough surface could be a
      novel alternative implant material for orthopedic and dental applications.

PMID- 22419870
TI  - Skin regeneration with conical and hair follicle structure of deep second-degree
      scalding injuries via combined expression of the EPO receptor and beta common
      receptor by local subcutaneous injection of nanosized rhEPO.
AB  - BACKGROUND: Acceleration of skin regeneration is still an unsolved problem in the
      clinical treatment of patients suffering from deep burns and scalds. Although
      erythropoietin (EPO) has a protective role in a wide range of organs and cells
      during ischemia and after trauma, it has been recently discovered that EPO is not
      tissue-protective in the common beta subunit receptor (betaCR) knockout mouse.
      The protective capacity of EPO in tissue is mediated via a heteroreceptor complex
      comprising both the erythropoietin receptor (EPOR) and betaCR. However, proof of
      coexpression of these heterogenic receptors in regenerating skin after burns is
      still lacking. METHODS: To understand the role of nanosized recombinant human
      erythropoietin (rhEPO) in wound healing, we investigated the effects of
      subcutaneous injections of EPO on skin regeneration after deep second-degree
      scalding injuries. Our aim was to determine if joint expression of EPOR and
      betaCR is a prerequisite for the tissue-protective effect of rhEPO. The
      efficiency in wound regeneration in a skin scalding injury mouse model was
      examined. A deep second-degree dermal scald injury was produced on the backs of
      20 female Balb/c mice which were subsequently randomized to four experimental
      groups, two of which received daily subcutaneous injections of rhEPO. At days 7
      and 14, the mice were sacrificed and the effects of rhEPO were analyzed with
      respect to grade of re-epithelialization (wound closure) and stage of epidermal
      maturation. This was investigated using different histological parameters of
      epithelial covering, such as depth of the epidermal layer, epidermal
      stratification, and presence of conical and hair follicle structures. RESULTS:
      Expression of EPOR, betaCR, and growth hormone receptor at the mRNA and protein
      levels was demonstrated with reverse transcriptase polymerase chain reaction and
      Western blot analysis. After rhEPO treatment, the rate of re-epithelialization of
      the scalding injury was increased and the time to final wound closure was
      reduced. In addition, the quality of regenerated skin was improved. In this
      investigation, for the first time, we demonstrated coexpression of EPOR and
      betaCR at the RNA and protein levels in vivo using a deep second-degree scalding
      injury mouse model. These results highlight the potential role of rhEPO in the
      improved treatment of burns patients, which might be crucial for the development
      of innovative new therapy regimes. CONCLUSION: Local injection of nanosized rhEPO
      directly to the injury site rather than systemic administration for deep second
      degree scalding injuries achieved complete skin regeneration with conical and
      hair follicle structure via combined expression of EPOR and betaCR.

PMID- 22419871
TI  - Cell responses to two kinds of nanohydroxyapatite with different sizes and
      crystallinities.
AB  - INTRODUCTION: Hydroxyapatite (HA) is the principal inorganic constituent of human
      bone. Due to its good biocompatibility and osteoconductivity, all kinds of HA
      particles were prepared by different methods. Numerous reports demonstrated that
      the properties of HA affected its biological effects. METHODS: Two kinds of
      nanohydroxyapatite with different sizes and crystallinities were obtained via a
      hydrothermal treatment method under different temperatures. It was found that at
      a temperature of 140 degrees C, a rod-like crystal (n-HA1) with a diameter of 23
      +/- 5 nm, a length of 47 +/- 14 nm, and crystallinity of 85% +/- 5% was produced,
      while at a temperature of 80 degrees C, a rod-like crystal (n-HA2) with a
      diameter of 16 +/- 3 nm, a length of 40 +/- 10 nm, and crystallinity of 65% +/-
      3% was produced. The influence of nanohydroxyapatite size and crystallinity on
      osteoblast viability was studied by MTT, scanning electron microscopy, and flow
      cytometry. RESULTS: n-HA1 gave a better biological response than n-HA2 in
      promoting cell growth and inhibiting cell apoptosis, and also exhibited much more
      active cell morphology. Alkaline phosphatase activity for both n-HA2 and n-HA1
      was obviously higher than for the control, and no significant difference was
      found between n-HA1 and n-HA2. The same trend was observed on Western blotting
      for expression of type I collagen and osteopontin. In addition, it was found by
      transmission electron microscopy that large quantities of n-HA2 entered into the
      cell and damaged the cellular morphology. Release of tumor necrosis factor alpha
      from n-HA2 was markedly higher than from n-HA1, indicating that n-HA2 might
      trigger a severe inflammatory response. CONCLUSION: This work indicates that not
      all nanohydroxyapatite should be considered a good biomaterial in future clinical
      applications.

PMID- 22419872
TI  - In vivo tumor targeting of gold nanoparticles: effect of particle type and dosing
      strategy.
AB  - Gold nanoparticles (GNPs) have gained significant interest as nanovectors for
      combined imaging and photothermal therapy of tumors. Delivered systemically, GNPs
      preferentially accumulate at the tumor site via the enhanced permeability and
      retention effect, and when irradiated with near infrared light, produce
      sufficient heat to treat tumor tissue. The efficacy of this process strongly
      depends on the targeting ability of the GNPs, which is a function of the
      particle's geometric properties (eg, size) and dosing strategy (eg, number and
      amount of injections). The purpose of this study was to investigate the effect of
      GNP type and dosing strategy on in vivo tumor targeting. Specifically, we
      investigated the in vivo tumor-targeting efficiency of pegylated gold nanoshells
      (GNSs) and gold nanorods (GNRs) for single and multiple dosing. We used Swiss
      nu/nu mice with a subcutaneous tumor xenograft model that received intravenous
      administration for a single and multiple doses of GNS and GNR. We performed
      neutron activation analysis to quantify the gold present in the tumor and liver.
      We performed histology to determine if there was acute toxicity as a result of
      multiple dosing. Neutron activation analysis results showed that the smaller GNRs
      accumulated in higher concentrations in the tumor compared to the larger GNSs. We
      observed a significant increase in GNS and GNR accumulation in the liver for
      higher doses. However, multiple doses increased targeting efficiency with minimal
      effect beyond three doses of GNPs. These results suggest a significant effect of
      particle type and multiple doses on increasing particle accumulation and on tumor
      targeting ability.

PMID- 22419873
TI  - Novel magnetic fibrin hydrogel scaffolds containing thrombin and growth factors
      conjugated iron oxide nanoparticles for tissue engineering.
AB  - Novel tissue-engineered magnetic fibrin hydrogel scaffolds were prepared by the
      interaction of thrombin-conjugated iron oxide magnetic nanoparticles with
      fibrinogen. In addition, stabilization of basal fibroblast growth factor (bFGF)
      was achieved by the covalent and physical conjugation of the growth factor to the
      magnetic nanoparticles. Adult nasal olfactory mucosa (NOM) cells were seeded in
      the transparent fibrin scaffolds in the absence or presence of the free or
      conjugated bFGF-iron oxide nanoparticles. The conjugated bFGF enhanced
      significantly the growth and differentiation of the NOM cells in the fibrin
      scaffolds, compared to the same or even five times higher concentration of the
      free bFGF. In the presence of the bFGF-conjugated magnetic nanoparticles, the
      cultured NOM cells proliferated and formed a three-dimensional interconnected
      network composed mainly of tapered bipolar cells. The magnetic properties of
      these matrices are due to the integration of the thrombin- and bFGF-conjugated
      magnetic nanoparticles within the scaffolds. The magnetic properties of these
      scaffolds may be used in future work for various applications, such as magnetic
      resonance visualization of the scaffolds after implantation and reloading the
      scaffolds via magnetic forces with bioactive agents, eg, growth factors bound to
      the iron oxide magnetic nanoparticles.

PMID- 22419874
TI  - Evaluation of uptake and transport of cationic and anionic ultrasmall iron oxide
      nanoparticles by human colon cells.
AB  - Nanoparticles (NPs) are in clinical use or under development for therapeutic
      imaging and drug delivery. However, relatively little information exists
      concerning the uptake and transport of NPs across human colon cell layers, or
      their potential to invade three-dimensional models of human colon cells that
      better mimic the tissue structures of normal and tumoral colon. In order to gain
      such information, the interactions of biocompatible ultrasmall superparamagnetic
      iron oxide nanoparticles (USPIO NPs) (iron oxide core 9-10 nm) coated with either
      cationic polyvinylamine (aminoPVA) or anionic oleic acid with human HT-29 and
      Caco-2 colon cells was determined. The uptake of the cationic USPIO NPs was much
      higher than the uptake of the anionic USPIO NPs. The intracellular localization
      of aminoPVA USPIO NPs was confirmed in HT-29 cells by transmission electron
      microscopy that detected the iron oxide core. AminoPVA USPIO NPs invaded three
      dimensional spheroids of both HT-29 and Caco-2 cells, whereas oleic acid-coated
      USPIO NPs could only invade Caco-2 spheroids. Neither cationic aminoPVA USPIO NPs
      nor anionic oleic acid-coated USPIO NPs were transported at detectable levels
      across the tight CacoReadyTM intestinal barrier model or the more permeable mucus
      secreting CacoGobletTM model.

PMID- 22419875
TI  - Construction of paclitaxel-loaded poly (2-hydroxyethyl methacrylate)-g-poly
      (lactide)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine copolymer nanoparticle
      delivery system and evaluation of its anticancer activity.
AB  - BACKGROUND: There is an urgent need to develop drug-loaded biocompatible
      nanoscale packages with improved therapeutic efficacy for effective clinical
      treatment. To address this need, a novel poly (2-hydroxyethyl methacrylate)-poly
      (lactide)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine [PHEMA-g-(PLA-DPPE)]
      copolymer was designed and synthesized to enable these nanoparticles to be pH
      responsive under pathological conditions. METHODS: The structural properties and
      thermal stability of the copolymer was measured and confirmed by Fourier
      transform infrared spectroscopy, nuclear magnetic resonance, and
      thermogravimetric analysis. In order to evaluate its feasibility as a drug
      carrier, paclitaxel-loaded PHEMA-g-(PLA-DPPE) nanoparticles were prepared using
      the emulsion-solvent evaporation method. RESULTS: The PHEMA-g-(PLA-DPPE)
      nanoparticles could be efficiently loaded with paclitaxel and controlled to
      release the drug gradually and effectively. In vitro release experiments
      demonstrated that drug release was faster at pH 5.0 than at pH 7.4. The
      anticancer activity of the PHEMA-g-(PLA-DPPE) nanoparticles was measured in
      breast cancer MCF-7 cells in vivo and in vitro. In comparison with the free drug,
      the paclitaxel-loaded PHEMA-g-(PLA-DPPE) nanoparticles could induce more
      significant tumor regression. CONCLUSION: This study indicates that PHEMA-g-(PLA
      DPPE) nanoparticles are promising carriers for hydrophobic drugs. This system can
      passively target cancer tissue and release drugs in a controllable manner, as
      determined by the pH value of the area in which the drug accumulates.

PMID- 22419876
TI  - Physiologically based pharmacokinetic modeling of PLGA nanoparticles with varied
      mPEG content.
AB  - Biodistribution of nanoparticles is dependent on their physicochemical properties
      (such as size, surface charge, and surface hydrophilicity). Clear and systematic
      understanding of nanoparticle properties' effects on their in vivo performance is
      of fundamental significance in nanoparticle design, development and optimization
      for medical applications, and toxicity evaluation. In the present study, a
      physiologically based pharmacokinetic model was utilized to interpret the effects
      of nanoparticle properties on previously published biodistribution data.
      Biodistribution data for five poly(lactic-co-glycolic) acid (PLGA) nanoparticle
      formulations prepared with varied content of monomethoxypoly (ethyleneglycol)
      (mPEG) (PLGA, PLGA-mPEG256, PLGA-mPEG153, PLGA-mPEG51, PLGA-mPEG34) were
      collected in mice after intravenous injection. A physiologically based
      pharmacokinetic model was developed and evaluated to simulate the mass-time
      profiles of nanoparticle distribution in tissues. In anticipation that the
      biodistribution of new nanoparticle formulations could be predicted from the
      physiologically based pharmacokinetic model, multivariate regression analysis was
      performed to build the relationship between nanoparticle properties (size, zeta
      potential, and number of PEG molecules per unit surface area) and biodistribution
      parameters. Based on these relationships, characterized physicochemical
      properties of PLGA-mPEG495 nanoparticles (a sixth formulation) were used to
      calculate (predict) biodistribution profiles. For all five initial formulations,
      the developed model adequately simulates the experimental data indicating that
      the model is suitable for description of PLGA-mPEG nanoparticle biodistribution.
      Further, the predicted biodistribution profiles of PLGA-mPEG495 were close to
      experimental data, reflecting properly developed property-biodistribution
      relationships.

PMID- 22419877
TI  - Sentiment Analysis of Suicide Notes: A Shared Task.
AB  - This paper reports on a shared task involving the assignment of emotions to
      suicide notes. Two features distinguished this task from previous shared tasks in
      the biomedical domain. One is that it resulted in the corpus of fully anonymized
      clinical text and annotated suicide notes. This resource is permanently available
      and will (we hope) facilitate future research. The other key feature of the task
      is that it required categorization with respect to a large set of labels. The
      number of participants was larger than in any previous biomedical challenge task.
      We describe the data production process and the evaluation measures, and give a
      preliminary analysis of the results. Many systems performed at levels approaching
      the inter-coder agreement, suggesting that human-like performance on this task is
      within the reach of currently available technologies.

PMID- 22419880
TI  - Effect of orally administered dipterinyl calcium pentahydrate on oral glucose
      tolerance in diet-induced obese mice.
AB  - Calcium pterins have been shown to be significant immunotherapeutic agents in
      models of breast cancer, hepatitis B, and tuberculosis (Bacillus Calmette-Guerin
      mycobacteria). These compunds modulate the immuno-enzyme indoleamine 2,3
      dioxygenase (IDO) and the blood levels of several identified inflammatory
      cytokines. Recent research into the pathology of diabetes implicates inflammatory
      factors in the progression of the disease, leading the authors to study its
      possible control by one of the calcium pterins, dipterinyl calcium pentahydrate
      (DCP). The investigators tested DCP as a novel therapeutic for type 2 diabetes.
      Female C57BL/6 J mice with diet-induced obesity were fed a high-fat diet and were
      administered DCP in 0.4% carboxymethylcellulose for 21 days. Blood glucose was
      followed during the dosing period, and an oral glucose tolerance test (OGTT) was
      carried out on day 21. Measurements of plasma indoleamine 2,3-dioxygenase
      metabolites (tryptophan and kynurenine) and certain cytokines and chemokines were
      also taken. DCP 7 mg/kg/day reduced OGTT area under the curve (OGTT/ AUC) by 50%
      (P < 0.05). A significant multivariate regression (P = 0.013; R(2) = 0.571) of
      OGTT/ AUC was derived from DCP dosage and plasma Trp. Elevated plasma Trp
      concentration, likely from heterogeneity in diet and/or indoleamine 2,3
      dioxygenase activity, was found to correlate with higher OGTT/AUC diabetic
      measures, possibly via inhibition of histamine degradation. In conclusion, an
      optimum dose of DCP 7 mg/kg/day significantly improved the OGTT diabetic state in
      these female diet-induced obese mice.

PMID- 22419879
TI  - Targeted agents for the treatment of metastatic melanoma.
AB  - In the last year, the armamentarium of melanoma therapeutics has radically
      changed. Recent discoveries in melanoma biology and immunology have led to novel
      therapeutics targeting known oncogenes and immunotherapeutic antibodies. Phase
      III clinical trials of these agents have reported measurable and meaningful
      benefits to patients with metastatic disease. In this article, we review recent
      findings and discuss their significance in melanoma therapy. As our understanding
      of melanoma biology grows, this initial therapeutic success may be enhanced
      through the use of molecular markers to select patients, and new targeted
      immunotherapies in sequential or combination drug regimens.

PMID- 22419878
TI  - Emerging treatment options for the treatment of neuroblastoma: potential role of
      perifosine.
AB  - Achieving a cure for high-risk neuroblastoma, the most common extracranial solid
      tumor in children, remains a formidable task despite the recent addition of
      antibody-mediated anti-GD2 immunotherapy to established multimodality therapy.
      The PI3K/Akt pathway is a pivotal signaling pathway utilized by a plethora of
      receptor tyrosine kinases that contribute to the aggressive phenotype of high
      risk neuroblastoma. Akt is aberrantly activated in high-risk neuroblastoma and is
      therefore an attractive therapeutic target. Perifosine is the best-characterized
      Akt inhibitor in preclinical studies and in clinical trials in adults, although
      safety in children is not yet confirmed. It is a synthetic third-generation
      alkylphospholipid with good oral bioavailability and modest side effects.
      Perifosine targets the lipid-binding PH domain of Akt and inhibits the
      translocation of Akt to the cell membrane, an essential step for Akt activation.
      It decreases Akt phosphorylation and increases caspase-dependent apoptosis in
      neuroblastoma cell lines, inhibits growth of neuroblastoma xenografts, and
      overcomes RTK/ligand-mediated chemoresistance. It is currently being studied in
      two Phase I clinical trials in children with recurrent or refractory solid tumors
      including neuroblastoma. In the single agent trial (ClinicalTrials.gov identifier
      NCT00776867), maximum tolerated dose has not yet been reached and pharmacokinetic
      data has been accrued. In the second study (ClinicalTrials.gov identifier
      NCT01049841), patients are treated with a combination of perifosine and the mTOR
      inhibitor temsirolimus based on preclinical data showing synergy of the two
      agents, and the premise that direct Akt inhibition may overcome Akt activation
      secondary to mTOR inhibition. Based on results from adult trials, it is unlikely
      that perifosine alone will produce dramatic therapeutic effects against high-risk
      neuroblastoma. However, given the recent encouraging early-phase combination
      therapy results in adults with multiple myeloma and colorectal carcinoma,
      rational perifosine-containing combination regimens hold promise for
      neuroblastoma therapy. These will be explored after safety in children is
      established in Phase I studies.

PMID- 22419881
TI  - Negative association of acetate with visceral adipose tissue and insulin levels.
AB  - BACKGROUND: The composition of gut flora has been proposed as a cause of obesity,
      a major risk factor for type 2 diabetes. The objective of this study was to
      assess whether serum short chain fatty acids, a major by-product of fermentation
      in gut flora, are associated with obesity and/or diabetes-related traits (insulin
      sensitivity and secretion). METHODS: The association of serum short chain fatty
      acids levels with measures of obesity was assessed using body mass index,
      computerized tomography scan, and dual photon X-ray absorptiometry scan. Insulin
      sensitivity and insulin secretion were both determined from an oral glucose
      tolerance test and insulin sensitivity was also determined from a
      hyperinsulinemic euglycemic clamp. RESULTS: In this population of young, obese
      women, acetate was negatively associated with visceral adipose tissue determined
      by computerized tomography scan and dual photon X-ray absorptiometry scan, but
      not body mass index. The level of the short chain fatty acids acetate, but not
      propionate or butyrate, was also negatively associated with fasting serum insulin
      and 2 hour insulin levels in the oral glucose tolerance test. CONCLUSIONS: In
      this population, serum acetate was negatively associated with visceral adipose
      tissue and insulin levels. Future studies need to verify these findings and
      expand on these observations in larger cohorts of subjects.

PMID- 22419883
TI  - Thyroid dysfunction in pregnancy.
AB  - Timely treatment of thyroid disease during pregnancy is important in preventing
      adverse maternal and fetal outcomes. Thyroid abnormalities are very often
      subclinical in nature and not easily recognized without specific screening
      programs. Even mild maternal thyroid hormone deficiency may lead to
      neurodevelopment complications in the fetus. The main diagnostic indicator of
      thyroid disease is the measurement of serum thyroid-stimulating hormone and free
      thyroxine levels. Availability of gestation-age-specific thyroid-stimulating
      hormone thresholds is an important aid in the accurate diagnosis and treatment of
      thyroid dysfunction. Pregnancy- specific free thyroxine thresholds not presently
      available are also required. Large-scale intervention trials are urgently needed
      to assess the efficacy of preconception or early pregnancy screening for thyroid
      disorders. Accurate interpretation of both antepartum and postpartum levels of
      thyroid hormones is important in preventing pregnancy-related complication
      secondary to thyroid dysfunction. This article sheds light on the best ways of
      management of thyroid dysfunction during pregnancy in order to prevent any
      possible maternal or fetal complication.

PMID- 22419882
TI  - Health costs from hospitalization with H1N1 infection during the 2009-2010
      influenza pandemic compared with non-H1N1 respiratory infections.
AB  - BACKGROUND: The first positive patient with influenza A (H1N1) was recorded in
      March 2009 and the pandemic continued with new outbreaks throughout 2010. This
      study's objective was to quantify the total cost of inpatient care and identify
      factors associated with the increased cost of the 2009-2010 influenza A pandemic
      in comparison with nonviral respiratory infection. METHODS: In total, 133
      positive and 103 negative H1N1 patients were included from three tertiary care
      hospitals during the two waves of H1N1 in 2009 and 2010. The health costs for
      protective equipment and pharmaceuticals and hospitalization (medications,
      laboratory, and diagnostic tests) were compared between H1N1 positive and
      negative patients. RESULTS: The objective of the study was to quantify the means
      of daily and total costs of inpatient care. Overall, cost was higher for H1N1
      positive (?61,0117.72) than for H1N1-negative patients (?464,923.59). This was
      mainly due to the protection measures used and the prolonged hospitalization in
      intensive care units. In H1N1-negative patients, main contributors to cost
      included additional diagnostic tests due to concern regarding respiratory
      capacity and laboratory values, as well as additional radiologic and microbial
      culture tests. The mean duration of hospitalization was 841 days for H1N1
      positive and 829 days for negative patients. CONCLUSION: Cost was higher in H1N1
      patients, mainly due to the protection measures used and the increased duration
      of hospitalization in intensive care units. An automated system to monitor
      patients would be desirable to reduce cost in H1N1 influenza.

PMID- 22419884
TI  - Living alone, receiving help, helplessness, and inactivity are strongly related
      to risk of undernutrition among older home-dwelling people.
AB  - BACKGROUND: Being at risk of undernutrition is a global problem among older
      people. Undernutrition can be considered inadequate nutritional status,
      characterized by insufficient food intake and weight loss. There is a lack of
      Norwegian studies focusing on being at risk of undernutrition and self-care
      ability, sense of coherence, and health-related issues among older home-dwelling
      people. AIM: To describe the prevalence of being at risk of undernutrition among
      a group of older home-dwelling individuals in Norway, and to relate the results
      to reported self-care ability, sense of coherence, perceived health and other
      health-related issues. METHODS: A cross-sectional design was applied. A
      questionnaire with instruments for nutritional screening, self-care ability, and
      sense of coherence, and health-related questions was sent to a randomized sample
      of 450 persons (aged 65+ years) in southern Norway. The study group included 158
      (35.1%) participants. Data were analysed using statistical methods. RESULTS: The
      results showed that 19% of the participants were at medium risk of undernutrition
      and 1.3% at high risk. Due to the low response rate it can be expected that the
      nonparticipants can be at risk of undernutrition. The nutritional at-risk group
      had lower self-care ability and weaker sense of coherence. Living alone,
      receiving help regularly to manage daily life, not being active and perceived
      helplessness emerged as predictors for being at risk of undernutrition. The
      results indicate difficulties in identifying people at nutritional risk and
      supporting self-care activities to maintain a good nutritional status.
      CONCLUSION: Health care professionals have to be able to identify older home
      dwelling people at risk of undernutrition, support self-care activities to enable
      people at risk to maintain a sufficient nutritional status, and be aware that
      older people living alone, who receive help, feel helpless, and are inactive are
      especially vulnerable.

PMID- 22419885
TI  - The interactions between hemostasis and resistance training: a review.
AB  - Physical inactivity is considered a risk factor for cardiovascular disease and is
      strongly associated with changes in arterial structure. Regular physical activity
      and exercise contributes to the prevention of coronary artery disease. Therefore,
      cardiovascular and resistance training improve hemostatic parameters and promote
      a less thrombotic blood profile. This review highlights the studies, mechanisms,
      and outcomes relating to the effectiveness of resistance training on the process
      of hemostasis. The Pubmed, Scopus, Medline, Scielo, Lilacs, Ibecs, and Cochrane
      databases were used to locate the original articles. Seventeen studies were found
      during the research process. Of these, ten articles were excluded. Those
      protocols using a high volume of training for young adults showed a greater
      fibrinolytic response, and training protocols with intensities above 80% of 1
      maximum repetition showed an increased platelet activity. In subjects with
      coronary artery disease, just one session of resistance training resulted in
      improvement in the fibrinolytic system (tissue plasminogen activator) without
      raising potential thrombotic markers.

PMID- 22419886
TI  - Phenotypic characterization of osteoarthritic osteocytes from the sclerotic
      zones: a possible pathological role in subchondral bone sclerosis.
AB  - Subchondral bone sclerosis is a well-recognised manifestation of osteoarthritis
      (OA). The osteocyte cell network is now considered to be central to the
      regulation of bone homeostasis; however, it is not known whether the integrity of
      the osteocyte cell network is altered in OA patients. The aim of this study was
      to investigate OA osteocyte phenotypic changes and its potential role in OA
      subchondral bone pathogenesis. The morphological and phenotypic changes of
      osteocytes in OA samples were investigated by micro-CT, SEM, histology,
      immunohistochemistry, TRAP staining, apoptosis assay and real-time PCR studies.
      We demonstrated that in OA subchondral bone, the osteocyte morphology was altered
      showing rough and rounded cell body with fewer and disorganized dendrites
      compared with the osteocytes in control samples. OA osteocyte also showed
      dysregulated expression of osteocyte markers, apoptosis, and degradative enzymes,
      indicating that the phenotypical changes in OA osteocytes were accompanied with
      OA subchondral bone remodelling (increased osteoblast and osteoclast activity)
      and increased bone volume with altered mineral content. Significant alteration of
      osteocytes identified in OA samples indicates a potential regulatory role of
      osteocytes in subchondral bone remodelling and mineral metabolism during OA
      pathogenesis.

PMID- 22419887
TI  - Isolation and identification of miRNAs in Jatropha curcas.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that play crucial regulatory roles by
      targeting mRNAs for silencing. To identify miRNAs in Jatropha curcas L, a
      bioenergy crop, cDNA clones from two small RNA libraries of leaves and seeds were
      sequenced and analyzed using bioinformatic tools. Fifty-two putative miRNAs were
      found from the two libraries, among them six were identical to known miRNAs and
      46 were novel. Differential expression patterns of 15 miRNAs in root, stem,
      leave, fruit and seed were detected using quantitative real-time PCR. Ten miRNAs
      were highly expressed in fruit or seed, implying that they may be involved in
      seed development or fatty acids synthesis in seed. Moreover, 28 targets of the
      isolated miRNAs were predicted from a jatropha cDNA library database. The miRNA
      target genes were predicted to encode a broad range of proteins. Sixteen targets
      had clear BLASTX hits to the Uniprot database and were associated with genes
      belonging to the three major gene ontology categories of biological process,
      cellular component, and molecular function. Four targets were identified for
      JcumiR004. By silencing JcumiR004 primary miRNA, expressions of the four target
      genes were up-regulated and oil composition were modulated significantly,
      indicating diverse functions of JcumiR004.

PMID- 22419888
TI  - Hydrogen sulfide mitigates cardiac remodeling during myocardial infarction via
      improvement of angiogenesis.
AB  - Exogenous hydrogen sulfide (H2S) leads to down-regulation of inflammatory
      responses and provides myocardial protection during acute ischemia/reperfusion
      injury; however its role during chronic heart failure (CHF) due to myocardial
      infarction (MI) is yet to be unveiled. We previously reported that H2S inhibits
      antiangiogenic factors such, as endostatin and angiostatin, but a little is known
      about its effect on parstatin (a fragment of proteinase-activated receptor-1, PAR
      1). We hypothesize that H2S inhibits parstatin formation and promotes VEGF
      activation, thus promoting angiogenesis and significantly limiting the extent of
      MI injury. To verify this hypothesis MI was created in 12 week-old male mice by
      ligation of left anterior descending artery (LAD). Sham surgery was performed
      except LAD ligation. After the surgery mice were treated with sodium hydrogen
      sulfide (30 MUmol/l NaHS, a donor for H2S, in drinking water) for 4 weeks. The LV
      tissue was analyzed for VEGF, flk-1 and flt-1, endostatin, angiostatin and
      parstatin. The expression of VEGF, flk-1 and flt-1 were significantly increased
      in treated mice while the level of endostatin, angiostatin and parstatin were
      decreased compared to in untreated mice. The echocardiography in mice treated
      with H2S showed the improvement of heart function compared to in untreated mice.
      The X-ray and Doppler blood flow measurements showed enhancement of cardiac
      angiogenesis in mice treated with H2S. This observed cytoprotection was
      associated with an inhibition of anti-angiogenic proteins and stimulation of
      angiogenic factors. We established that administration of H2S at the time of MI
      ameliorated infarct size and preserved LV function during development of MI in
      mice. These results suggest that H2S is cytoprotective and angioprotective during
      evolution of MI.

PMID- 22419889
TI  - Prognostic values of filamin-A status for topoisomerase II poison chemotherapy.
AB  - Filamin-A, also called Actin Binding Protein-280, is not only an essential
      component of the cytoskeleton networks, but also serves as the scaffold in
      various signaling networks. It has been shown that filamin-A facilitates DNA
      repair and filamin-A proficient cells are more resistant to ionizing radiation,
      bleomycin, and cisplatin. In this study, we assessed the role of filamin-A in
      modulating cancer cell sensitivity to Topo II poisons, including etoposide and
      doxorubicin. Intriguingly, we found that cells with filamin-A expression are more
      sensitive to Topo II poisons than those with defective filamin-A, and filamin-A
      proficient xenograft melanomas have better response to etoposide treatment than
      the filamin-A deficient tumors. This is associated with more potent induction of
      DNA double strand breaks (DSBs) by Topo II poisons in filamin-A proficient cells
      than the deficient cells. Although the expression of filamin-A enables cells a
      slightly stronger capability to repair DSB, the net outcome is that filamin-A
      proficient cells bear more DSBs due to the significantly enhanced DSB induction
      by Topo II poisons in these cells. We further found that filamin-A proficient
      cells have increased drug influx and decreased drug efflux, suggesting that
      filamin-A modulates the intra-cellular drug kinetics of Topo II poisons to
      facilitate the generation of DSB after Topo II poison exposure. These data
      suggest a novel function of filamin-A in regulating the pharmacokinetics of Topo
      II poisons, and that the status of filamin-A may be used as a prognostic marker
      for Topo II poisons based cancer treatments.

PMID- 22419890
TI  - The silencing of RECK gene is associated with promoter hypermethylation and poor
      survival in hepatocellular carcinoma.
AB  - BACKGROUND: To evaluate the promoter methylation status of RECK gene and mRNA
      expression in patients with hepatocellular carcinoma (HCC). METHODS: We analyzed
      RECK methylation by MSP, and RECK mRNA by real-time PCR in 74 HCC. The liver cell
      lines (7721, Chang and Hep-G2) were treated with 5-Aza-CdR and TSA. RESULTS: RECK
      mRNA were lower in HCC tissues (Mean (-?Ct) = -3.29) than that in Non-Hcc tissues
      (Mean (-?Ct) = -2.42). Expression of RECK was elevated in only 24 (32.43%) of the
      74 HCC patients but decreased (-??Ct<0) in 50 (67.57%) of the patients. RECK
      promoter was hypermethylated in 55.4% (41/74) of HCCs, and in only 17.6% (13/74)
      of Non-Hcc samples. RECK mRNA were lower in HCC patients with hypermethylation
      (?MI>=0.5) (Mean (-??Ct) = -1.75) than those with demethylation (?MI<0.5) (Mean (
      ??Ct) = 0.05), and there is a decreased tendency for RECK mRNA in HCC patients
      with promoter hypermethylation (p = 0.002). There was a significantly correlation
      found between RECK mRNA and poor survival after surgery. After treated by 5-Aza
      CdR and TSA, we found that RECK mRNA induced different changes in 7721, Chang and
      Hep-G2 cells. And RECK demethylation also induced by epigenetic inhibitors.
      CONCLUSION: The results suggested that the hypermethylation may lead to promoter
      silencing of RECK mRNA and associated with poor survival in HCC.

PMID- 22419891
TI  - OLFML3 expression is decreased during prenatal muscle development and regulated
      by microRNA-155 in pigs.
AB  - The Olfactomedin-like 3 (OLFML3) gene has matrix-related function involved in
      embryonic development. MicroRNA-155 (miR-155), 21- to 23-nucleotides (nt)
      noncoding RNA, regulated myogenesis by target mRNA. Our LongSAGE analysis
      suggested that OLFML3 gene was differently expressed during muscle development in
      pig. In this study, we cloned the porcine OLFML3 gene and detected its tissues
      distribution in adult Tongcheng pigs and dynamical expression in developmental
      skeletal muscle (12 prenatal and 10 postnatal stages) from Landrace (lean-type)
      and Tongcheng (obese-type) pigs. Subsequently, we analyzed the interaction
      between OLFML3 and miR-155. The OLFML3 was abundantly expressed in liver and
      pancreas, moderately in lung, small intestine and placenta, and weakly in other
      tissues and postnatal muscle. There were different dynamical expression patterns
      between Landrace and Tongcheng pigs during prenatal skeletal muscle development.
      The OLFML3 was down-regulated (33-50 days post coitus, dpc), subsequently up
      regulated (50-70 dpc), and then down-regulated (70-100 dpc) in Landrace pigs,
      while in Tongcheng pigs, it was down-regulated (33-50 dpc), subsequently up
      regulated (50-55 dpc) and then down-regulated (55-100 dpc). There was higher
      expression in Tongcheng than Landrace in prenatal muscle from 33 to 60 dpc, and
      opposite situation from 65 to 100 dpc. Dual luciferase assay and real time PCR
      documented that OLFML3 expression was regulated by miR-155 at mRNA level. Our
      research indicated that OLFML3 gene may affect prenatal skeletal muscle
      development and was regulated by miR-155. These finding will help understanding
      biological function and expression regulation of OLFML3 gene in mammal animals.

PMID- 22419893
TI  - Neoadjuvant Treatment of Breast Cancer.

PMID- 22419894
TI  - Neoadjuvant Therapy - What Have We Achieved in the Last 20 Years?
AB  - Neoadjuvant chemotherapy is the standard of care for patients with large,
      inoperable tumors or inflammatory breast cancer, but it is also increasingly
      considered for women with operable disease. Several randomized trials have
      demonstrated that anthracycline- and taxane-containing regimens in operable
      breast cancer were equally effective in terms of disease-free or overall survival
      regardless of whether they were administered postoperatively or preoperatively.
      Further neoadjuvant treatment allows for a higher rate of breast conserving
      surgery. Tumor responses in terms of pathologic complete remission after short
      term chemotherapy will probably only serve as a surrogate marker for long-term
      outcome in some molecular breast cancer subtypes like the triple-negative, HER2
      positive, and some luminal B subsets. Recent trials showed that in HER2-positive
      disease pCR rates were as high as 70% when 2 HER2-targeted agents were added to
      chemotherapy.

PMID- 22419892
TI  - The function of steroid receptor coactivator-1 in normal tissues and cancer.
AB  - In 1995, the steroid receptor coactivator-1 (SRC-1) was identified as the first
      authentic steroid receptor coactivator. Since then, the SRC proteins have
      remained at the epicenter of coregulator biology, molecular endocrinology and
      endocrine-related cancer. Cumulative works on SRC-1 have shown that it is
      primarily a nuclear receptor coregulator and functions to construct highly
      specific enzymatic protein complexes which can execute efficient and successful
      transcriptional activation of designated target genes. The versatile nature of
      SRC-1 enables it to respond to steroid dependent and steroid independent
      stimulation, allowing it to bind across many families of transcription factors to
      orchestrate and regulate complex physiological reactions. This review highlights
      the multiple functions of SRC-1 in the development and maintenance of normal
      tissue functions as well as its major role in mediating hormone receptor
      responsiveness. Insights from genetically manipulated mouse models and clinical
      data suggest SRC-1 is significantly overexpressed in many cancers, in particular,
      cancers of the reproductive tissues. SRC-1 has been associated with cellular
      proliferation and tumor growth but its major tumorigenic contributions are
      promotion and execution of breast cancer metastasis and mediation of resistance
      to endocrine therapies. The ability of SRC-1 to coordinate multiple signaling
      pathways makes it an important player in tumor cells' escape of targeted therapy.

PMID- 22419895
TI  - Trends and Novel Approaches in Neoadjuvant Treatment of Breast Cancer.
AB  - Breast cancer is the most prevalent malignant disease in women worldwide.
      Traditionally, surgical tumour resection was the primary step within the
      treatment algorithm of early stage disease; systemic therapy in order to reduce
      the rate of systemic recurrences followed. National Surgical Adjuvant Breast and
      Bowel Project (NSABP) trial B-18 found that pre- and postoperative administration
      of chemotherapy was equally effective. This study therefore established
      neoadjuvant chemotherapy as a valid treatment option, as the breast conservation
      rate is increased. Modern neoadjuvant regimens encompassing anthracyclines and
      taxanes yield pathological complete response (pCR) rates of around 20%, with
      higher efficacy observed in triple-negative tumours. The antibody trastuzumab is
      the first targeted agent established in neoadjuvant regimens for the treatment of
      Her2-positive breast cancer, as it raised pCR rates up to 50%. Novel approaches
      are aiming to increase the efficacy of neoadjuvant therapy. Inclusion of
      capecitabine might further increase pCR rates in selected patients, although data
      are not unanimous throughout the respective clinical trials. In patients
      harbouring BRCA-1 germline mutations, platinum derivatives are apparently
      promising. Novel Her2-targeted agents such as lapatinib and pertuzumab are
      currently under investigation in several clinical trials, while the role of
      bevacizumab, a monoclonal antibody inhibiting angiogenesis, awaits future
      clarification.

PMID- 22419896
TI  - Comparison of Clinical Features and Treatment Outcome of Breast Cancers in Young
      and Elderly Chinese Patients.
AB  - BACKGROUND: This study aimed to investigate the clinicopathological features and
      prognosis of operable breast cancers in young and elderly Chinese women. 
      PATIENTS AND METHODS: This study included 209 patients aged <=35 years and 213
      patients aged >=60 but <70 years, who received treatment between January 2000 and
      December 2004. The clinicopathological features, molecular subtypes, therapeutic
      strategies, and prognosis were evaluated.  RESULTS: Tumor size was of significant
      difference between the 2 groups (p = 0.018), with more T2 and T3 tumors in the
      young group and more lymph node involvement in young patients with stage T1
      tumors (p = 0.033). There were more triple-negative and less luminal A tumors in
      the young group (p = 0.018). 47.1% of tumors were not detected by mammography in
      the young group as compared to 5.5% in the elderly group (p < 0.001). More
      patients received chemotherapy in the young group (p < 0.001) and preferred
      breast-conserving surgery (p = 0.031). The 6-year disease-free survival (DFS) was
      80 and 66% in the elderly and the young group, respectively (p = 0.001), but no
      difference was seen in overall survival.  CONCLUSIONS: Compared with elderly
      women, young breast cancer patients have different clinicopathological features
      and molecular subtypes, and poorer DFS. Furthermore, the insidious onset of
      breast cancer in young women suggests that clinicians should pay more attention
      to young women with breast abnormalities.

PMID- 22419897
TI  - Breast Cancer-Associated Thrombotic Microangiopathy.
AB  - BACKGROUND: Thrombotic microangiopathy (TMA) is defined as thrombocytopenia and
      microangiopathic hemolytic anemia. Cancer-associated TMA, a rare but fatal
      condition, seems an entity distinct from classical thrombotic thrombocytopenic
      purpura (TTP)/hemolytic uremic syndrome (HUS).  PATIENTS AND METHODS: All
      patients with breast cancer-associated TMA treated at our institution between
      2003 and 2008 were analyzed retrospectively. To elucidate pathophysiological
      mechanisms, we measured the serum activity of the metalloprotease ADAMTS13. 
      RESULTS: 8 patients were identified. All showed bone marrow infiltration of
      breast cancer as well as thrombocytopenia, schistocytes, and hemolytic anemia.
      ADAMTS13 activity was mildly decreased in 4/6 patients (20-108%, normal range 30
      120%), but none showed severely low levels as is characteristic of classical TTP.
      6 patients were treated with anthracycline-containing fractionated chemotherapy,
      5/6 patients experienced partial response. Overall survival was 13 months.
      Fractionated chemotherapy was well tolerated.  CONCLUSIONS: Cancer-associated TMA
      has an underlying mechanism different from classical TTP. While bone marrow
      infiltration might be of major relevance, ADAMTS13 deficiency seems to be an
      epiphenomenon. Fractionated chemotherapy resulted in higher remission rates and
      comparatively long survival.

PMID- 22419898
TI  - Clinicopathological Characteristics and Survival Analysis of 87 Male Breast
      Cancer Cases.
AB  - BACKGROUND: The aim of this study was to investigate the clinicopathologic
      characteristics, therapy methods, and prognosis of male breast cancer.  PATIENTS
      AND METHODS: We retrospectively analyzed the clinicopathological characteristics,
      recurrence or metastasis, and survival information of 87 male breast cancer
      patients. Statistical analysis included the Kaplan-Meier method to analyze
      survivals, log-rank to compare curves between groups, and Cox regression for
      multivariate prognostic analysis. A p value of <0.05 was considered statistically
      significant.  RESULTS: 5-year disease free survival (DFS) and 5-year overall
      survival (OS) were 66.3 and 77.0%, respectively. Monofactorial analysis showed
      tumor size, stage, lymph node involvement, and adjuvant chemotherapy to be
      prognostic factors with regard to 5-year DFS and 5-year OS. Multivariate Cox
      regression analysis showed tumor size, stage, and adjuvant chemotherapy to be
      independent prognostic factors with regard to 5-year DFS and 5-year OS. 
      CONCLUSION: Male breast cancer has a lower incidence rate and poor prognosis.
      Invasive ductal carcinoma is the main pathologic type. Operation-based combined
      therapy is the standard care for these patients. Tumor size, stage, and adjuvant
      chemotherapy are independent prognostic factors. More emphasis should be placed
      on early diagnosis and early therapy, and adjuvant chemotherapy may improve
      survival.

PMID- 22419899
TI  - Modifiable Risk of Breast Cancer in Northeast Iran: Hope for the Future. A Case
      Control Study.
AB  - BACKGROUND: Breast cancer is the most common cancer in women. Its prevalence is
      increasing annually by 2%. The determination of modifiable risk factors has been
      the subject of various studies. The aim of this study was to determine risk
      factors of breast cancer in women in Golestan Province.  PATIENTS AND METHODS:
      This case-control study was conducted among women with breast cancer recorded in
      the cancer registry system between 2004 and 2006 (n = 134), and their age-matched
      healthy neighbors (n = 133). Data were statistically analyzed.  RESULTS: Age at
      marriage, menarche and pregnancy, breast feeding, positive family history,
      marital status, and educational level were not significantly correlated with risk
      of breast cancer, but age at menopause (< 46.6 years) was significantly
      correlated (95% confidence interval 1.15-7.37; p = 0.021). Live births, still
      births, and infant deaths were not significantly different between the 2 groups.
      For other variables, such as smoking history, no odds ratio was calculated. 
      CONCLUSION: Results show that there is no significant correlation between
      variables and risk of breast cancer in our population, except for age at
      menopause. A large cohort study is recommended.

PMID- 22419900
TI  - Multicenter Phase II Study with Weekly Bendamustine and Paclitaxel as First- or
      Later-Line Therapy in Patients with Metastatic Breast Cancer: RiTa II Trial.
AB  - The combination of bendamustine (B) and paclitaxel (P) as anthracycline-free
      treatment option in patients with advanced breast cancer has been evaluated in
      the previous RiTa I trial. The regimen of weekly B 70 mg/m(2) and P 90 mg/m(2)
      with a pause every 4th week was established as an effective regimen with low
      toxicity. The aim of the present RiTa II study was to investigate the potential
      of BP as anthracycline-free combination therapy. The primary objective was to
      determine the progression-free survival (PFS); secondary endpoints were safety,
      tolerability, overall response rate (ORR) and overall survival (OS). 26 patients
      were available, 15 received BP as first-line, 11 as beyond first-line treatment.
      27% patients had triple-negative breast cancer (TNBC). Median PFS and OS were 7.3
      months (95% confidence interval (CI): 5.5-10.9) and 14.9 months (95% CI: 9.9
      22.9), respectively. The 1-year PFS rate was 20.3% and the 1-year OS rate 71.2%.
      The ORR was 42.3%, including 4 complete and 7 partial remissions. TNBC patients
      reached an ORR of 71.4%. Anthracycline-pretreated patients showed an ORR of
      43.8%, confirming bendamustine's lack of cross-resistance to anthracycline
      agents. BP represents a favorable option with moderate toxicity in pretreated
      metastatic breast cancer and offers a possibility for application in
      anthracycline-pretreated and TNBC patients.

PMID- 22419901
TI  - Nipple Retractor to Correct Inverted Nipples.
AB  - BACKGROUND: Inverted nipples are a common problem and a challenging clinical
      condition to repair. Multiple methods have been reported to correct inverted
      nipples, most of which will destroy breastfeeding function.  PATIENTS AND
      METHODS: We have designed a simple nipple retractor to correct inverted nipples.
      A total of 53 patients with 95 inverted nipples underwent an operation in which
      the nipples were retracted into a normal position and fixated with the nipple
      retractor and wires under local anesthesia. Nipple retractors were to be worn for
      6 months. Postoperatively, the patients were invited to follow-up on the 1st day,
      the 7th day, after 1 month, 3 months and 6 months, and yearly thereafter. Wire
      adjustments were performed as needed. Mean follow-up was 11.9 months (range 8-18
      months).  RESULTS: Improvement occurred in all patients and was sustained in all
      cases throughout the follow-up period. The total complication rate was 5.26%
      (5/95). The main complications included depigmentation (2.11%, 2/95), areolar
      ulcer (2.11%, 2/95), and wire dislocation (1.05%, 1/95).  CONCLUSION: The nipple
      retractor is a simple tool with which severely inverted nipples can be
      successfully corrected with a low complication rate. Close follow-up and careful
      postoperative care are important to avoid complications.

PMID- 22419902
TI  - Can We Keep the 'PROMISE'? AGO Breast Commission: Commentary on Recent Evidence
      Regarding LHRH Analogues for the Preservation of Ovarian Function.
AB  - Recently reported data from the German ZORO trial and the Italian PROMISE-GIM6
      trial have come to different conclusions. The AGO Breast Commission does not
      recommend the general use of luteinizing hormone-releasing hormone (LHRH)
      analogues for the preservation of ovarian function. Instead, we distinguish
      between patients with hormone receptor-negative and hormone receptor-positive
      disease. This article reviews the AGO recommendations in light of the ZORO and
      PROMISE-GIM6 data. In conclusion, separate recommendations are needed for the
      prevention of ovarian failure and for fertility preservation because the trials
      did not investigate fertility rate as a primary outcome measure. The results from
      not yet published trials such as OPTION and POEM may shed new light on the role
      of LHRH analogues.

PMID- 22419903
TI  - Parotid Gland Metastasis of Breast Cancer: Case Report and Review of the
      Literature.
AB  - BACKGROUND: Parotid gland metastasis in breast cancer is extremely rare, and only
      14 cases have been reported between 1982 and 2010.  CASE REPORT: A 67-year-old
      female patient was diagnosed with invasive lobular carcinoma of the left breast.
      Although clinical staging was T1N3M1 (stage IV), the tumor experienced a complete
      response to chemotherapy. We therefore performed a mastectomy followed by
      radiotherapy, and continued administration of trastuzumab. However, 11 months
      later, the patient complained of a swelling in the left parotid gland. Histology
      following a partial parotidectomy revealed a parotid gland metastasis from the
      breast.  CONCLUSION: Treatment with capecitabine in addition to trastuzumab,
      which is one of the strategies applied in HER2-positive breast cancer, was
      effective in our patient. Analysis of the 14 cases of parotid gland metastasis
      from the breast reported between 1982 and 2010 revealed that the metastasis may
      occur not by direct lymphatic but by hematogenous spread.

PMID- 22419905
TI  - Normal Breastfeeding after Breast Reconstruction in a Patient with Poland's
      Syndrome.
AB  - BACKGROUND: Poland's syndrome is a rare congenital non-inherited anomaly that
      usually manifests itself during adolescence and is characterized by absence or
      deficient development of one of the breasts. To our knowledge, no case of
      breastfeeding after reconstruction surgery in patients with Poland's syndrome has
      been described.  CASE REPORT: A 22-year-old female patient with Poland's syndrome
      underwent breast reconstruction. The procedure performed consisted of rotation of
      a myocutaneous flap harvested from the ipsilateral latissimus dorsi muscle, which
      was subsequently attached to the anterior thoracic wall to create a pouch and
      place a 300-ml round textured cohesive silicone gel-filled breast implant. 5
      years later the patient got pregnant, and 1 year after delivery she is still
      breastfeeding normally with both breasts.  CONCLUSION: Reconstruction surgery
      with the latissimus dorsi muscle and a prosthesis was shown to be a potential and
      safe solution to achieve improvement of breast symmetry and to provide confidence
      and comfort in relation to self-image and, moreover, the ability to breastfeed.

PMID- 22419904
TI  - Fetal Renal Insufficiency Following Trastuzumab Treatment for Breast Cancer in
      Pregnancy: Case Report und Review of the Current Literature.
AB  - Some drugs are known for their fetal nephrotoxicity and should be avoided during
      pregnancy. We report on a pregnant woman suffering from breast cancer who
      received a weekly neoadjuvant trastuzumab (Herceptin((r))) therapy from 15 weeks
      of gestation onward, in addition to a 3-weekly carboplatin/docetaxel
      chemotherapy. Fetal renal insufficiency with anhydramnios and missing
      visualization of the fetal bladder developed at 21 weeks. After discontinuation
      of trastuzumab and repeated instillation of amniotic fluid, the amount of
      amniotic fluid remained stable after 24 weeks of gestation. After caesarean
      section at 34 weeks because of fetal growth restriction, the renal function of
      the neonate was normal postnatally. In accordance with the current literature,
      our case shows a reversible adverse effect of trastuzumab on the fetal renal
      function and confirms the current recommendation that trastuzumab in pregnancy
      should be avoided. In pregnancies exposed to trastuzumab, treatment should be
      discontinued and the fetus should be closely monitored, with particular attention
      to the amniotic fluid and the fetal bladder volume, as these reflect fetal renal
      function.

PMID- 22419906
TI  - Conditional RARalpha knockout mice reveal acute requirement for retinoic acid and
      RARalpha in homeostatic plasticity.
AB  - All-trans retinoic acid (RA) plays important roles in brain development through
      regulating gene transcription. Recently, a novel post-developmental role of RA in
      mature brain was proposed. Specifically, RA rapidly enhanced excitatory synaptic
      transmission independent of transcriptional regulation. RA synthesis was induced
      when excitatory synaptic transmission was chronically blocked, and RA then
      activated dendritic protein synthesis and synaptic insertion of homomeric GluA1
      AMPA receptors, thereby compensating for the loss of neuronal activity in a
      homeostatic fashion. This action of RA was suggested to be mediated by its
      canonical receptor RARalpha but no genetic evidence was available. Thus, we here
      tested the fundamental requirement of RARalpha in homeostatic plasticity using
      conditional RARalpha knockout (KO) mice, and additionally performed a structure
      function analysis of RARalpha. We show that acutely deleting RARalpha in neurons
      eliminated RA's effect on excitatory synaptic transmission, and inhibited
      activity blockade-induced homeostatic synaptic plasticity. By expressing various
      RARalpha rescue constructs in RARalpha KO neurons, we found that the DNA-binding
      domain of RARalpha was dispensable for its role in regulating synaptic strength,
      further supporting the notion that RA and RARalpha act in a non-transcriptional
      manner in this context. By contrast, the ligand-binding domain (LBD) and the mRNA
      binding domain (F-domain) are both necessary and sufficient for the function of
      RARalpha in homeostatic plasticity. Furthermore, we found that homeostatic
      regulation performed by the LBD/F-domains leads to insertion of calcium-permeable
      AMPA receptors. Our results confirm with unequivocal genetic approaches that RA
      and RARalpha perform essential non-transcriptional functions in regulating
      synaptic strength, and establish a functional link between the various domains of
      RARalpha and their involvement in regulating protein synthesis and excitatory
      synaptic transmission during homeostatic plasticity.

PMID- 22419907
TI  - Explicit behavioral detection of visual changes develops without their implicit
      neurophysiological detectability.
AB  - Change blindness is a failure of reporting major changes across consecutive
      images if separated, e.g., by a brief blank interval. Successful change detection
      across interrupts requires focal attention to the changes. However, findings of
      implicit detection of visual changes during change blindness have raised the
      question of whether the implicit mode is necessary for development of the
      explicit mode. To this end, we recorded the visual mismatch negativity (vMMN) of
      the event-related potentials (ERPs) of the brain, an index of implicit pre
      attentive visual change detection, in adult humans performing an oddball-variant
      of change blindness flicker task. Images of 500 ms in duration were presented
      repeatedly in continuous sequences, alternating with a blank interval (either 100
      ms or 500 ms in duration throughout a stimulus sequence). Occasionally (P = 0.2),
      a change (referring to color changes, omissions, or additions of objects or their
      parts in the image) was present. The participants attempted to explicitly (via
      voluntary button press) detect the occasional change. With both interval
      durations, it took 10-15 change presentations in average for the participants to
      eventually detect the changes explicitly in a sequence, the 500 ms interval only
      requiring a slightly longer exposure to the series than the 100 ms one.
      Nevertheless, prior to this point of explicit detectability, the implicit
      detection of the changes vMMN could only be observed with the 100 ms intervals.
      These findings of explicit change detection developing with and without implicit
      change detection may suggest that the two modes of change detection recruit
      independent neural mechanisms.

PMID- 22419908
TI  - Biliverdin reductase: more than a namesake - the reductase, its Peptide
      fragments, and biliverdin regulate activity of the three classes of protein
      kinase C.
AB  - The expanse of human biliverdin reductase (hBVR) functions in the cells is
      arguably unmatched by any single protein. hBVR is a Ser/Thr/Tyr-kinase, a
      scaffold protein, a transcription factor, and an intracellular transporter of
      gene regulators. hBVR is an upstream activator of the insulin/IGF-1 signaling
      pathway and of protein kinase C (PKC) kinases in the two major arms of the
      pathway. In addition, it is the sole means for generating the antioxidant
      bilirubin-IXalpha. hBVR is essential for activation of ERK1/2 kinases by upstream
      MAPKK-MEK and by PKCdelta, as well as the nuclear import and export of ERK1/2.
      Small fragments of hBVR are potent activators and inhibitors of the ERK kinases
      and PKCs: as such, they suggest the potential application of BVR-based technology
      in therapeutic settings. Presently, we have reviewed the function of hBVR in cell
      signaling with an emphasis on regulation of PKCdelta activity.

PMID- 22419910
TI  - The acute effects of a single session of expiratory muscle strength training on
      blood pressure, heart rate, and oxygen saturation in healthy adults.
AB  - Expiratory muscle strength training (EMST) is a rehabilitative program that has
      been tested for outcomes related to respiratory muscle strength, cough, swallow,
      and voice function in healthy young adult, elderly individuals, and in patients
      with progressive neurodegenerative disease. Because EMST has been used in patient
      care, the associated cardiovascular responses during EMST are of importance. This
      study investigated the changes in systolic blood pressure (SBP), diastolic blood
      pressure (DBP), heart rate (HR), and oxygen saturation (SpO(2)) during one
      session of EMST in healthy, young adults as a preliminary study of device safety.
      Thirty-one participants completed a single session of 25 trials with the EMST
      device. Valsalva maneuvers were performed at the beginning and at the end of the
      EMST trials for task comparison. The SBP, DBP, HR, and SpO(2) were recorded at
      the baseline and after completing the following tasks: a Valsalva maneuver, 12
      trials using the EMST device, 13 trials using the EMST device, and 5 min of rest
      following the EMST session. A mixed linear model tested for changes across the
      six time points. The results indicated no significant change of SBP, DBP, HR, or
      SpO(2) during or following the EMST trials or after performing the Valsalva
      maneuver. The results suggest that EMST does not elicit significant fluctuations
      of blood pressure, HR, and SpO(2) in healthy young adults even when considering
      the effects of covariates on the outcomes measures.

PMID- 22419911
TI  - Erythropoietin treatment enhances muscle mitochondrial capacity in humans.
AB  - Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis
      in cardiac muscle along with enhanced mitochondrial capacity in mice. We
      hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal
      muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans. In
      six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8
      weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS
      was quantified by high-resolution respirometry in saponin-permeabilized muscle
      fibers obtained from biopsies of the vastus lateralis before and after rhEpo
      treatment. OXPHOS was determined with the mitochondrial complex I substrates
      malate, glutamate, pyruvate, and complex II substrate succinate in the presence
      of saturating ADP concentrations, while maximal electron transport capacity (ETS)
      was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from
      92 +/- 5 to 113 +/- 7 pmol.s(-1).mg(-1)) and ETS (107 +/- 4 to 143 +/- 14 pmol.s(
      1).mg(-1), p < 0.05), demonstrating that Epo treatment induces an upregulation of
      OXPHOS and ETS in human skeletal muscle.

PMID- 22419909
TI  - Enzymes of the AKR1B and AKR1C Subfamilies and Uterine Diseases.
AB  - Endometrial and cervical cancers, uterine myoma, and endometriosis are very
      common uterine diseases. Worldwide, more than 800,000 women are affected annually
      by gynecological cancers, as a result of which, more than 360,000 die. During
      their reproductive age, about 70% of women develop uterine myomas and 10-15%
      suffer from endometriosis. Uterine diseases are associated with aberrant
      inflammatory responses and concomitant increased production of prostaglandins
      (PG). They are also related to decreased differentiation, due to low levels of
      protective progesterone and retinoic acid, and to enhanced proliferation, due to
      high local concentrations of estrogens. The pathogenesis of these diseases can
      thus be attributed to disturbed PG, estrogen, and retinoid metabolism and
      actions. Five human members of the aldo-keto reductase 1B (AKR1B) and 1C (AKR1C)
      superfamilies, i.e., AKR1B1, AKR1B10, AKR1C1, AKR1C2, and AKR1C3, have roles in
      these processes and can thus be implicated in uterine diseases. AKR1B1 and AKR1C3
      catalyze the formation of PGF2alpha, which stimulates cell proliferation. AKR1C3
      converts PGD2 to 9alpha,11beta-PGF2, and thus counteracts the formation of 15
      deoxy-PGJ2, which can activate pro-apoptotic peroxisome-proliferator-activated
      receptor gamma. AKR1B10 catalyzes the reduction of retinal to retinol, and thus
      lessens the formation of retinoic acid, with potential pro-differentiating
      actions. The AKR1C1-AKR1C3 enzymes also act as 17-keto- and 20-ketosteroid
      reductases to varying extents, and are implicated in increased estradiol and
      decreased progesterone levels. This review comprises an introduction to uterine
      diseases and AKR1B and AKR1C enzymes, followed by an overview of the current
      literature on the AKR1B and AKR1C expression in the uterus and in uterine
      diseases. The potential implications of the AKR1B and AKR1C enzymes in the
      pathophysiologies are then discussed, followed by conclusions and future
      perspectives.

PMID- 22419912
TI  - Relationship of dropout and psychopathology in a high school sample in Mexico.
AB  - School dropout has significant consequences for both individuals and societies.
      Only 21% of adults in Mexico achieve the equivalent of a high school education.
      We examined the relationship between school dropout and self-reported psychiatric
      symptoms in a middle school in a suburb of Mexico City. We used binomial logistic
      regression to examine the odds ratio (OR) of school dropout associated with
      students' self-reported psychopathology. Two-hundred thirty-seven students
      participated in the study. Psychosis [OR = 8.0 (95% confidence interval, CI: 1.7
      37.2)], depression [OR = 4.7 (95% CI: 2.2-9.7)], tic disorders [OR = 3.7 (95% CI:
      1.4-9.5)], ADHD [OR = 3.2 (95% CI: 1.5-6.4)], and social phobia [OR = 2.6 (95%
      CI: 1.2-5.8)] were associated with increased risk of school dropout after
      controlling for age and gender as covariates. Our study suggested that students'
      self-reported psychopathology is associated with increased school dropout in
      Mexico. ADHD and depression may be particularly useful childhood psychiatric
      disorders to target with public health interventions because they explain the
      greatest amount of the variance in school dropout of child psychiatric disorders.

PMID- 22419913
TI  - Prediction and control in a dynamic environment.
AB  - The present study compared the accuracy of cue-outcome knowledge gained during
      prediction-based and control-based learning in stable and unstable dynamic
      environments. Participants either learnt to make cue-interventions in order to
      control an outcome, or learnt to predict the outcome from observing changes to
      the cue values. Study 1 (N = 60) revealed that in tests of control, after a short
      period of familiarization, performance of Predictors was equivalent to
      Controllers. Study 2 (N = 28) showed that Controllers showed equivalent task
      knowledge when to compared to Predictors. Though both Controllers and Predictors
      showed good performance at test, overall Controllers showed an advantage. The cue
      outcome knowledge acquired during learning was sufficiently flexible to enable
      successful transfer to tests of control and prediction.

PMID- 22419914
TI  - Direct Diagnosis is Superior to Risk Factor Prediction Tools for Management of
      Vessel Wall Disease.

PMID- 22419915
TI  - Managing your wine fermentation to reduce the risk of biogenic amine formation.
AB  - Biogenic amines are nitrogenous organic compounds produced in wine from amino
      acid precursors mainly by microbial decarboxylation. The concentration of
      biogenic amines that can potentially be produced is dependent on the amount of
      amino acid precursors in the medium, the presence of decarboxylase positive
      microorganisms and conditions that enable microbial or biochemical activity such
      as the addition of nutrients to support the inoculated starter cultures for
      alcoholic and malolactic fermentation (MLF). MLF can be conducted using co
      inoculation or an inoculation after the completion of alcoholic fermentation that
      may also affect the level of biogenic amines in wine. This study focused on the
      impact of the addition of complex commercial yeast and bacterial nutrients and
      the use of different MLF inoculation scenarios on the production of biogenic
      amines in wine. Results showed that the addition of complex nutrients to real
      grape must could potentially increase histamine concentrations in wine. The same
      experiment in synthetic grape must showed a similar trend for putrescine and
      cadaverine. The effect of different MLF inoculation scenarios was examined in two
      cultivars, Pinotage and Shiraz. Conflicting results was obtained. In the Shiraz,
      co-inoculation resulted in lower biogenic amine concentrations after MLF compared
      to before MLF, while the concentration was higher in the Pinotage. However, the
      production of biogenic amines was affected more by the presence of decarboxylase
      positive lactic acid bacteria than by the addition of complex nutrients or the
      inoculation scenario.

PMID- 22419916
TI  - Structural biology for virus research.

PMID- 22419918
TI  - The use of deep friction massage with olive oil as a means of prevention and
      treatment of sports injuries in ancient times.
AB  - The aim of this research was to analyse the use of olive oil as a means of
      prevention and treatment of sports injuries in the ancient world. The method
      adopted was based on a thorough study of Greek and world literature. Writings of
      major ancient philosophers and physicians such as Hippocrates, Aristotle,
      Philostratus, and Lucian have been analysed in depth. According to the results,
      the use of massage, together with olive oil rub, helped to reduce muscle fatigue,
      to remove lactic acid, and to prevent the occurrence of sports injuries through
      flexibility provided to the skin of athletes. The therapeutic use of oil in the
      ancient world was fully recognized; and as a result Athenian athlothetes
      (sponsors of sporting events) provided free oil to all sport facilities where
      athletes could make free use of it [1].

PMID- 22419917
TI  - Are we getting to lipid targets in real life?

PMID- 22419919
TI  - Endovascular repair of thoracic aortic aneurysm.
AB  - A thoracic aortic aneurysm (TAA) is a potentially life-threatening condition with
      structural weakness of the aortic wall, which can progress to arterial dilatation
      and rupture. Today, both an increasing awareness of vascular disease and the
      access to tomographic imaging facilitate the diagnosis of TAA even in an
      asymptomatic stage. The risk of rupture for untreated aneurysms beyond a diameter
      of 5.6 cm ranges from 46% to 74% and the two-year mortality rate is greater than
      70%, with most deaths resulting from rupture. Treatment options include surgical
      and non-surgical repair to prevent aneurysm enlargement and rupture. While most
      cases of ascending aortic involvement are subject to surgical repair (partially
      with valve-preserving techniques), aneurysm of the distal arch and descending
      thoracic aorta are amenable to emerging endovascular techniques as an alternative
      to classic open repair or to a hybrid approach (combining debranching surgery
      with stent grafting) in an attempt to improve outcomes.

PMID- 22419920
TI  - Cyclooxygenase-2 expression and its association with thyroid lesions.
AB  - Cyclooxygenase (COX), also known as prostaglandin H synthase, catalyses the
      formation of prostaglandins from arachidonic acid. It can be expressed in
      response to various stimuli, such as hormones, mitogens, cytokines, other
      inflammatory mediators and growth factors. The product of COX-2 activity has been
      implicated in carcinogenesis by promoting angiogenesis, inhibiting apoptosis,
      increasing cell invasion and stimulating cell proliferation. It has also been
      proved that the regular intake of non-steroidal anti-inflammatory drugs (NSAIDs)
      decreases the risk of developing colon and breast cancers. Thus, it speaks for an
      important role of COX-2 in growth processes of various types of neoplasms. The
      connection between COX-2 activity and carcinogenesis has also been examined in
      human thyroid neoplasms. COX-2 overexpression has been reported in thyroid
      cancers and also in inflammatory conditions. In consequence there is significant
      interest whether COX-2 could be of importance as a molecular marker of malignancy
      in the case of thyroid carcinoma.

PMID- 22419921
TI  - Interactive effects of endogenous morphine, nitric oxide, and ethanol on
      mitochondrial processes.
AB  - Positive evolutionary pressure has preserved the ability to synthesize chemically
      authentic morphine, albeit in homeopathic concentrations, throughout animal
      phyla. The prototype catecholamine dopamine (DA) serves as an essential chemical
      intermediate in morphine biosynthesis both in plants and animals, thereby
      providing considerable insight into the roles reciprocal "morphinergic" and
      catecholamine regulation of diverse physiological processes. Primordial, multi
      potential cell types, before the emergence of specialized plant and animal
      cells/organ systems, required selective mechanisms to limit their responsiveness
      to environmental noise. Accordingly, cellular systems that emerged with the
      potential for recruitment of the free radical gas nitric oxide (NO) as a multi
      faceted autocrine/paracrine signaling molecule were provided with extremely
      positive evolutionary advantages. Endogenous "morphinergic" in concert with NO
      coupled signaling systems have evolved as autocrine/paracrine regulators of
      metabolic homeostasis, energy metabolism, mitochondrial respiration and energy
      production. Basic physiological processes involving "morphinergic"/NO-coupled
      regulation of cardiovascular mitochondrial function, with special emphasis on the
      interactive effects of ethanol, are discussed within the context of our review.

PMID- 22419922
TI  - Efficacy of Setarud (IMODTM), a novel electromagnetically-treated multi-herbal
      compound, in mouse immunogenic type-1 diabetes.
AB  - INTRODUCTION: The aim of this study was to evaluate the effects and mechanisms of
      Setarud (IMODTM) as a multi-herbal medicinal formula on a mouse model of type 1
      diabetes.  METERIAL AND METHODS: Autoimmune diabetes was induced by multiple low
      dose intraperitoneal injection of 40 mg/kg of streptozotocin (STZ) for five
      consecutive days. IMODTM was administered at an effective dose of 20 mg/kg/day
      for 21 days. After 21 days of treatment, the pancreases of the animals were
      separated and homogenized. In the pancreas tissue, the level of lipid
      peroxidation as thiobarbituric acid reactive substances (TBARS), total
      antioxidant power as ferric reducing ability of pancreas (FRAP), myeloperoxidase
      (MPO), and the concentrations of interleukin-1 (IL-1beta) and tumour necrosis
      factor-alpha (TNF-alpha) were evaluated. Glucose changes were tested in the
      blood. Microscopic changes in the pancreas were followed by histological
      examinations. RESULTS: No significant difference was found between IMODTM and
      diabetic control groups in blood glucose pattern. STZ-exposed mice showed a
      significant increase in pancreatic TBARS, MPO, IL-1beta, and TNF-alpha levels,
      along with a significant decrease in FRAP value. Co-administration of IMODTM
      significantly improved all the mentioned parameters disrupted by STZ
      administration except for blood glucose and histological changes. CONCLUSION:
      IMODTM could ameliorate oxidative and immunological distresses of type-1
      immunogenic diabetes but could not normalize blood glucose. Further studies are
      recommended to clarify the effects of IMODTM on immunological factors to address
      whether this new agent could be applied in diabetes prevention or therapy.

PMID- 22419923
TI  - Effects of clodronate combined with hydroxyapatite on multi-directional
      differentiation of mesenchymal stromal cells.
AB  - INTRODUCTION: Bisphosphonates (BPs) can be locally used to improve the
      osteogenesis around hydroxyapatite (HA) implants. However, there are almost no
      reports discussing the effects of BPs in the bonding state with HA on bone
      mesenchymal stromal cells (BMSCs). Clodronate is a BP widely used in clinical
      practice. This study was designed to evaluate the effects of clodronate combined
      with HA on BMSCs' multi-directional differentiation. MATERIAL AND METHODS: The HA
      and clodronate-HA complex were prepared. BMSCs were isolated from Sprague-Dawley
      rat bone marrow and then the cells were cultured with both HA and clodronate-HA.
      The method of transcriptional and translational assay (MTT) and multi-directional
      induction (including osteogenic, adipogenic, and myogenic differentiation) were
      used to evaluate the effect of clodronate-HA on BMSC differentiation. RESULTS:
      Scanning electron microscopy indicated active proliferation of the cells on
      clodronate-HA and HA. MTT of BMSCs cultured on clodronate-HA and HA demonstrated
      no significant differences between the two groups. BMSCs differentiated into
      osteocytes, adipocytes, and myocytes after being cultured with both clodronate-HA
      and HA. This indicated that BMSCs still retained multi-directional capability.
      The alkaline phosphatase activity of osteogenic induced BMSCs of both groups had
      no significant difference. However, there was a significant difference in total
      protein found between them. CONCLUSIONS: The results suggest that clodronate in
      the bonding state with HA has no obvious inhibition of the proliferation and
      activity of BMSCs on the complex, and there was no evidence of a negative effect
      on multi-directional capability of the BMSCs.

PMID- 22419924
TI  - In vitro neural/glial differentiation potential of periodontal ligament stem
      cells.
AB  - INTRODUCTION: It is known that periodontal ligament stem cells (PDLSCs) can
      differentiate into cementoblast-like cells, adipocytes and collagen-forming
      cells. However, whether PDLSCs are able to differentiate into Schwann cells and
      which method is best for their neural induction remain unknown. We attempted to
      determine whether PDLSCs possessed the potential for neural differentiation in
      vitro. MATERIALS AND METHODS: We isolated and multiplied PDLSCs from periodontal
      ligaments obtained from the teeth (n = 24) of 8-month-old beagle dogs. Four
      protocols with different chemicals and growth factors were adopted to induce the
      PDLSCs to differentiate into Schwann cells. Immunochemistry, RT-PCR and qRT-PCR
      were performed to investigate the in vitro neural differentiation potential of
      PDLSCs. RESULTS: We compared the 4 different protocols and showed that all 4
      protocols could successfully induce PDLSCs to express nestin, GFAP and S100,
      markers for Schwann cells. Further, qRT-PCR revealed relative differences in the
      expression levels of these 3 genes in differentiated PDLSCs obtained by different
      protocols. CONCLUSIONS: We conclude that PDLSCs have neural/glial differentiation
      potential in vitro and that neural/glial differentiation can be induced in PDLSCs
      if suitable protocols are followed. We also found that supplementing the growth
      medium with suitable growth factors is more effective than applying chemicals
      alone. While nerve growth factor is more effective than platelet-derived growth
      factor for inducing neural/glial differentiation in PDLSCs, pre-induction of
      PDLSCs with dimethyl sulphoxide yields better results than those obtained with
      all-trans-retinoic acid.

PMID- 22419925
TI  - Prospective population studies of incident heart failure without data on baseline
      left ventricular ejection fraction.
AB  - INTRODUCTION: Left ventricular ejection fraction (LVEF) is a predictor of
      incident heart failure (HF). However, baseline LVEF is often unavailable in
      population studies of HF.  METERIAL AND METHODS: Of the 5324 Cardiovascular
      Health Study (CHS) participants free of baseline HF, 143 (3%) had LVEF < 45% and
      1091 (21%) developed HF during 13 years of follow-up. Using public-use copies of
      the CHS data, we compared two predictor models of incident HF, with and without
      adjustment for baseline LVEF. RESULTS: Baseline impaired LVEF was a strong
      independent predictor of incident HF (adjusted hazard ratio, 2.78; P < 0.001) but
      had no impact on the direction, magnitude or significance of independent
      associations of the other predictors of incident HF such as age, sex, race,
      coronary artery disease, hypertension and diabetes. CONCLUSION: Baseline LVEF is
      an important predictor for incident HF but is not essential in population studies
      of risk factors for incident HF.

PMID- 22419926
TI  - Different diagnostic criteria significantly affect the rates of hypertension in
      18-year-old high school students.
AB  - INTRODUCTION: Childhood hypertension is defined based on the normative
      distribution of blood pressure (BP), but from the age of 18 years high BP is
      diagnosed using adult criteria. We compared the rates of diagnosis of
      hypertension in a group of 18-year-old subjects using BP percentiles and the
      adult criteria. MATERIAL AND METHODS: Blood pressure was measured by registered
      nurses in 1472 18-year-old high-school students (780 men and 692 women). Also
      weight, height and waist circumference were recorded. RESULTS: The prevalence of
      hypertension was 9% (16.2% in men and 0.9% in women, p < 0.001) using adult cut
      off values and 14.7% (21.9% in men and 6.6% in women, p < 0.001) using percentile
      charts. Obesity was diagnosed in 2.4% and overweight in 13% of subjects,
      respectively. The relative risk ratio of diagnosing hypertension according to the
      adult criteria in overweight or obese subjects was 2.94 (95% CI 2.25-3.86) in men
      and 6.44 (95% CI 3.51-11.82) in women. CONCLUSIONS: Our study indicates high
      prevalence of hypertension in 18-year-old students - especially in men - and the
      importance of obesity as a risk factor of hypertension. The use of percentile
      charts instead of adult cut-off values increases the prevalence of hypertension
      in men by 35% from 16.2% to 21.9% and in women more than 7 times, i.e. from 0.9%
      to 6.6%. It seems reasonable to use higher (i.e. 98(th)) percentile values for
      definition of high blood pressure.

PMID- 22419927
TI  - Changes in attainment of lipid goals by general practitioners and specialists in
      patients at high cardiovascular risk in Hungary during 2004-2008.
AB  - INTRODUCTION: Lipid-lowering therapy should achieve target levels. We assessed
      the change of the achievement of targets and the mean low-density lipoprotein
      cholesterol (LDL-C) levels in high-risk Hungarian patients. MATERIAL AND METHODS:
      Six studies performed with patients of general practitioners (GPs) and
      specialists between 2004 and 2008 were evaluated: 9,508 patients from GPs and
      2809 from specialist practices (total 12,317). RESULTS: During this 4-year period
      the LDL-C level decreased by 0.73 mmol/l and the LDL-C goal achievement rate
      increased from 14 to 32% in patients treated by GPs. LDL-C showed a decrease of
      0.48 mmol/l and the goal achievement rate changed from 20 to 43% in patients
      treated by specialists. In the majority of the patients not achieving the LDL-C
      goal (57% for specialists and 89% for GPs) there was no modification in the
      current therapy. In addition to emphasizing the priority of LDL-C lowering, we
      should also strive for residual risk reduction, which means raising high-density
      lipoprotein cholesterol (HDL-C) and lowering triglyceride levels. There was no
      significant improvement in HDL-C or triglyceride levels during the examined
      period. CONCLUSION: More attention needs to be paid to changing treatment of
      patients to achieve target levels.

PMID- 22419928
TI  - Dyslipidaemia in hypertensive obese type 2 diabetic patients in Jamaica.
AB  - INTRODUCTION: Hypertension and obesity are common problems among diabetic
      patients accelerating progression of vascular diabetic complications. MATERIALS
      AND METHODS: A two-stage stratified random sampling design was used, and
      individuals aged 15 years and over were interviewed. This cross-sectional study
      evaluated lipid abnormalities of 117 obese type 2 diabetic patients (28 males and
      89 females), and 56 hypertensive obese type 2 diabetic patients (22 males and 34
      females). Total cholesterol (TC), triglycerides (TG), low-density lipoprotein
      cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C) and high
      density lipoprotein cholesterol (HDL-C) concentrations were assayed using
      standard biochemical methods. RESULTS: Hypertensive obese type 2 diabetic females
      had significantly higher mean serum concentrations of TC (p = 0.043), TG (p =
      0.046), LDL-C (p= 0.040), TC/HDL-C ratio (p = 0.001) and LDL-C/HDL-C ratio (p =
      0.003) compared with hypertensive obese non-diabetic females. Similar results
      were found in hypertensive obese type 2 diabetic males compared with hypertensive
      obese non-diabetic males. Hypertensive obese type 2 diabetic females had
      significantly higher serum TC, TG and TC/HDL-C ratio (p < 0.05) than hypertensive
      obese type 2 diabetic males. Hypertensive obese type 2 diabetic females had
      significantly higher mean serum concentrations of TG (p = 0.03) and TC (p = 0.01)
      than obese type 2 diabetic females. There was a significant association between
      blood glucose and LDL-C concentrations in type 2 diabetic subjects (r = 0.36; p<
      0.05). CONCLUSION: Obese hypertensive type 2 diabetic females are exposed more
      profoundly to risk factors including atherogenic dyslipidaemia compared with
      males.

PMID- 22419929
TI  - Altered transcriptional activity of gene encoding GAPDH in peripheral blood
      mononuclear cells from patients with cardiac syndrome X - an important part in
      pathology of microvascular angina?
AB  - INTRODUCTION: Cardiac syndrome X (CSX) is characterized by anginal pain with ECG
      suggestive of ischaemia and normal coronary arteries at angiography. Pathology of
      CSX involves microvascular dysfunction and is possibly linked with metabolic
      syndrome. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an enzyme involved
      in glycolysis. The GAPDH gene is a "housekeeping" gene and is used for
      normalization in quantitative gene expression assays. The aim of the study was to
      evaluate GAPDH gene expression in CSX. MATERIAL AND METHODS: The study was
      performed in 35 CSX patients and 10 control subjects. mRNA was extracted from
      peripheral blood mononuclears and the mRNA was assessed by QRT-PCR. RESULTS:
      GAPDH gene expression was enhanced in CSX patients vs. controls (93022 +/-23837
      copies/MUg vs. 1067 +/-240 copies/MUg respectively; p < 0.001). Moreover,
      transcriptional activity of the GAPDH gene was heterogeneous within the CSX
      group. CONCLUSIONS: GAPDH gene expression is markedly enhanced in CSX, which
      reflects carbohydrate metabolism disturbances and makes the GAPDH gene unsuitable
      as an endogenous control in patients with CSX.

PMID- 22419930
TI  - Assessment of a single monomorphic ventricular ectopy from the right ventricular
      outflow tract in standard and high resolution electrocardiogram.
AB  - INTRODUCTION: High-resolution electrocardiography (ECG-CREM) is a method based on
      digital electrocardiography. In order to facilitate the interpretation of the
      Crem records the technique of vectorcardiography was used. In comparison the
      origin of the ventricular premature complexes (VPCs) could be estimated based on
      a standard 12-lead electrocardiogram. The aim of the study was to assess the
      point of origin of the VPCs in ECG-CREM and correlate it with standard
      electrocardiography (ECG-Stand). MATERIAL AND METHODS: Our study included 26
      patients (16 females, 10 males), aged 51-83 years (avg. 58.1 +/-12.3), who
      presented with recurrent, during at least 6 months' observation, VPCs. The point
      of origin of VPCs was compared in both methods. RESULTS: The performed analysis
      of collected ECG-Stand records revealed the presence of arrhythmogenic focal
      points in six different locations (1, 3, 5, 7, 8, 9). However, we did not affirm
      their presence in points 2,4,6. They were most commonly located in RVOT zones 8
      (30.7%), 9 (23.0%), 5 (23.0%), and most seldom in zones 1, 3, 7 (7.6% each). In
      the simultaneous record of ECG-CREM with a single VPC it was confirmed that the
      FPb zone was activated the most frequently (40.0%); the next in relation to
      frequency were SD and ST (20.0%). Less frequent VPCs have their origin in Crem
      zones SP, FPa and SB (6.6%). CONCLUSIONS: Electrocardiogram of high signal
      resolution (ECG-CREM) might be useful in recognition of the origin of ventricular
      premature complexes from RVOT.

PMID- 22419931
TI  - Acute effects of different levels of continuous positive airway pressure on
      cardiac autonomic modulation in chronic heart failure and chronic obstructive
      pulmonary disease.
AB  - INTRODUCTION: Non-invasive ventilation may improve autonomic modulation and
      ventilatory parameters in severely disabled patients. The aim of the present
      study was to evaluate the physiological influence of acute treatment with
      different levels of continuous positive airway pressure (CPAP) on the autonomic
      balance of heart and respiratory responses in patients with stable chronic
      obstructive pulmonary disease (COPD) and chronic heart failure (CHF). MATERIALS
      AND METHODS: A COPD group (n = 10), CHF group (n = 8) and healthy subjects (n =
      10) were evaluated. The participants were randomized to receive three different
      levels of CPAP on the same day: sham ventilation (Sham), 5 cmH(2)0 (CPAP5) and 10
      cmH(2)0 (CPAP10) for 10 min. Respiratory rate, end tidal carbon dioxide
      (E(T)CO(2)), peripheral oxygen saturation (SpO(2)), heart rate (HR), blood
      pressure and heart rate variability in the time and frequency domains were
      measured during spontaneous breathing and under the sham, CPAP5 and CPAP10
      conditions. RESULTS: All groups experienced a reduction in E(T)CO(2) values
      during treatment with CPAP (p < 0.05). CPAP increased SpO(2) and HR in the COPD
      group (p < 0.05). The COPD group also had lower RMSSD values during treatment
      with different levels of CPAP when compared to the control group (p < 0.05). In
      the CHF group, CPAP5 and CPAP10 increased the SDNN value (p < 0.05). CPAP10
      reduced the SDNN value in the COPD group (p < 0.05). CONCLUSION: The findings
      suggest that CPAP may cause improvements in the neural control of heart rate in
      patients with stable COPD and CHF. For each patient, the "best CPAP level" should
      be defined as the best respiratory response and autonomic balance.

PMID- 22419932
TI  - Speeding up coeliac disease diagnosis in cardiological settings.
AB  - INTRODUCTION: High prevalence of coeliac disease (CD) has been reported among
      patients with idiopathic dilated cardiomyopathy (DCM). We evaluated the
      feasibility and diagnostic accuracy of screening for CD by rapid test of anti
      transglutaminase antibodies in the cardiology outpatients' clinic. MATERIAL AND
      METHODS: We screened the blood samples of 104 patients with DCM, 44 of their
      first-degree relatives, 63 diseased controls and 101 healthy controls for the
      presence of anti-transglutaminase antibodies in a drop of whole blood using a
      rapid assay. This test was compared to the enzyme-linked immunosorbent assay and
      the anti-endomysium antibody test. RESULTS: Our rapid test was positive in three
      (2.9%) DCM patients, in one (2%) relative and in one (1%) healthy control. These
      subjects were positive at both control assays. Two DCM patients had iron
      deficient anaemia. The healthy relative was asymptomatic, while the healthy
      control experienced extreme asthenia. The relative refused intestinal biopsy,
      while the others showed histological evidence of CD. During the gluten-free diet,
      the patient with the worst left ventricular ejection fraction (LVEF) underwent
      heart transplant, and LVEF values improved in the other two. Anaemia and
      tiredness resolved in all patients. CONCLUSION: Early detection of CD in a
      cardiological setting allows prompt treatment with a gluten-free diet of gluten
      dependent complaints with potential benefits for the course of DCM.

PMID- 22419933
TI  - Morphogenetic aspects of the septomarginal trabecula in the human heart.
AB  - INTRODUCTION: The septomarginal trabecula is a constant element of the anatomy of
      the human heart, which connects the interventricular septum and the anterior wall
      of the right ventricle. Considering the diversity of opinions about the structure
      and numerous studies suggesting its important role in haemodynamics and
      conduction of electrical impulses in the heart, we decided to study this element
      in detail. MATERIAL AND METHODS: The research was conducted on 220 human hearts.
      Attention was mainly paid to the structure and topography of the trabecula. Its
      relation to the anterior papillary muscle was also a part of the study. RESULTS:
      The presence of this morphologically diverse element was confirmed in each of the
      studied hearts. In most cases the trabecula originated from the upper part of the
      interventricular septum, separating at an angle increasing proportionally to the
      number of branches of the crista supraventricularis as well as the number of
      secondary trabeculae. The criteria established for the study, which included the
      course of the trabecula in the lumen of the right ventricle and its relation to
      the anterior papillary muscle, let us distinguish 4 types of septomarginal
      trabecula (I, II, III, IV). The most common was type III, the undivided
      trabecula, tightly connecting with the anterior papillary muscle. CONCLUSIONS:
      Based on the results of the following study we propose a hypothesis on the
      genesis of respective parts of the septomarginal trabecula and a plausible
      sequence of changes they undergo during human ontogenesis and phylogenesis of the
      primates.

PMID- 22419934
TI  - Serum neutrophil gelatinase-associated lipocalin as a marker of kidney function
      in pregnancy - useful or doubtful?
AB  - INTRODUCTION: The aim of the study was to assess whether neutrophil gelatinase
      associated lipocalin (NGAL) and cystatin C could reflect kidney function in
      pregnant healthy women. MATERIAL AND METHODS: The studies were performed on 130
      healthy pregnant women (n = 63, 3(rd) trimester; n = 21, 2(nd) trimester; n = 46,
      1(st) trimester) and 30 healthy female volunteers. Serum NGAL, cystatin C, IL-6,
      and hs-CRP were assayed using commercially available kits. RESULTS: Serum
      cystatin C rose steadily during the pregnancy, whereas NGAL rose in the 2(nd)
      trimester, then decreased in the 3(rd) trimester. In univariate analysis, NGAL
      correlated with serum cystatin C, number of pregnancies, white blood cell count,
      total iron-binding capacity (TIBC), ferritin, and IL-6, and tended to correlate
      with eGFR. In multiple regression analysis the only predictor of serum NGAL was
      cystatin C. CONCLUSIONS: Serum NGAL in pregnancy might reflect subclinical
      inflammation rather than kidney function. It seems that NGAL, similarly to
      cystatin C, is not useful to monitor renal function in pregnancy.

PMID- 22419935
TI  - The use of whey protein concentrate in management of chronic hepatitis C virus -
      a pilot study.
AB  - INTRODUCTION: Whey protein contains biologically active ingredients that can
      prevent and attenuate disease besides being nutritive. The aim of the study was
      to clarify the effects of oral administration of whey protein on viral load and
      host defence mechanisms, in particular, phagocytic function of neutrophils,
      selected immunomodulatory cytokines and serum inflammatory markers, in
      compensated chronic hepatitis C virus (HCV) patients. MATERIAL AND METHODS:
      Twenty-seven HCV patients (20 males and 7 females) recruited from the hepatology
      clinic of the Theodor Bilharz Research Institute (TBRI) were given whey protein
      concentrate (WPC) twice daily for two months. In addition, 15 age and sex matched
      healthy participants were included in the study, as a control group. Neutrophil
      phagocytic activity, serum intercellular adhesion molecule (sICAM), interleukin-2
      (IL-2), nitric oxide (NO), as well as HCV-RNA levels and routine investigations
      were determined for patients, before and after WPC supplementation and once for
      the control group. RESULTS: There was a significant decrease in viral load and
      markers of active inflammation, alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST), while serum albumin, total leucocyte counts and absolute
      neutrophil counts showed significant elevation accompanied by improvement of
      neutrophil phagocytic activity after WPC supplementation compared to pre-treated
      levels. The oral WPC supplementation was well tolerated without any serious
      adverse events. CONCLUSIONS: Oral supplementation of WPC has promising results as
      a new therapeutic strategy against HCV and its sequelae by decreasing the viral
      load and active inflammation as well as improving the synthetic capacity of the
      liver and the phagocytic function of neutrophils, in these patients.

PMID- 22419936
TI  - The analysis of prognostic factors affecting post-radiation acute reaction after
      conformal radiotherapy for non-small cell lung cancer.
AB  - INTRODUCTION: The aim was to evaluate the risk of acute side effects in the lung
      after 3-dimensional conformal radiotherapy (3D-CRT) in patients treated for non
      small cell lung cancer (NSCLC). An attempt was made to single out clinical
      factors and factors related to treatment technique which may induce acute post
      radiation pneumonitis. MATERIAL AND METHODS: The analysis concerned 34
      consecutive patients who underwent radical radiation therapy for NSCLC. Intensity
      of early toxicity was evaluated using modified RTOG/EORTC toxicity score. The
      endpoint for this analysis was the occurrence of radiation pneumonitis of grade 2
      or higher. Factors related to treatment techniques were included in the
      statistical analysis. RESULTS: Fifty-three percent of patients included in the
      study suffered from acute post-radiation pneumonitis. The results of the study
      revealed the existence of lung tissue sensitivity to low doses of ionizing
      radiation. The multivariate analysis showed that total lung volume receiving a
      low dose of 10 Gy increased the risk of post-radiation pneumonitis (p = 0.01).
      CONCLUSIONS: Acute post-radiation pneumonitis was a relevant clinical problem in
      patients who underwent radical radiotherapy for non-small cell lung cancer. The
      lung volume receiving a dose of 10 Gy was the most important dosimetric factor
      which influenced the post-radiation acute pneumonitis.

PMID- 22419937
TI  - The influence of pre-emptive analgesia on postoperative analgesia and its
      objective evaluation.
AB  - INTRODUCTION: The evaluation of pain intensity is still a subject of research.
      Mostly psychological evaluations are used. We started to conduct biochemical
      evaluation in animal experiments. Now we present biochemical evaluation in
      postoperative pain in man. MATERIAL AND METHODS: In 67 patients herniotomy was
      done. For pre-emptive analgesia morphine and pethidine were used and the
      following indicators were measured: visual analogue scale (VAS), measurement of
      lipid spectra, saccharides and proteins, thioredoxin, super-oxide dismutase
      (SOD), glutathione peroxidase (GPx) and NAD(P)H-oxidase (NOX), and free radicals
      using electron paramagnetic resonance (EPR). Blood samples were taken and tested:
      before pre-medication and intervention, 4 h after and 24 h after intervention.
      RESULTS: Free radicals (FR) increased in individual samples during the
      postoperative course in pethidine and without pre-medication. After application
      of morphine the FR were insignificantly reduced. Statistically significant
      differences were found in albumin, prealbumin, apolipoprotein A, total
      cholesterol, atherosclerotic index, CRP, glucose, and thioredoxin (p <= 0.001). A
      greater difference was seen in VAS values between morphine and pethidine
      premedications (p <= 0.001). CONCLUSIONS: It was proved that the biochemical
      markers of lipid, protein and saccharide metabolisms and free radicals as well as
      singlet oxygen can serve as very good indicators of the intensity of pain and
      nociception. In patients it was proved that pre-emptive analgesia plays an
      important role in reducing the intensity of postoperative pain. From the three
      modalities of pre-emptive analgesia morphine represents the best solution.

PMID- 22419938
TI  - The association between CBS 844ins68 polymorphism and head and neck squamous cell
      carcinoma risk - a case-control analysis.
AB  - INTRODUCTION: Susceptibility to head and neck squamous cell carcinoma may be
      modified by functional polymorphisms in genes involved in the folate pathway,
      such as cystathionine beta-synthase (CBS). The CBS 844ins68 polymorphism is
      associated with DNA methylation changes and cancer development. MATERIAL AND
      METHODS: A case-control retrospective study was conducted in 322 patients with
      head and neck squamous cell carcinoma and in 531 control subjects without cancer.
      The polymerase chain reaction-restriction fragment length polymorphism technique
      was used to genotype the polymorphism. For statistical analysis, chi(2) test was
      conducted to examine whether the genotypic frequency of CBS 844ins68 was in Hardy
      Weinberg equilibrium and multiple logistic regression was used for comparisons
      between groups, and for interactions between the polymorphism and risk factors
      and clinical histopathological parameters. RESULTS: No significant difference in
      CBS 844ins68 genotypic distribution was observed between the groups. Age > 50
      years, male gender and tobacco consumption were predictors of the disease with
      increased risk of 7.89 (95% CI: 5.56-11.21), 2.49 (95% CI: 1.72-3.62), 6.44 (95%
      CI: 4.63-8.96) and 2.29 times (95% CI: 1.71-3.06) respectively. There was no
      association between the distribution of the CBS 844ins68 genotype and risk
      factors for this disease. According to clinical histopathological parameters, CBS
      884ins68 polymorphism presented high frequency in oral cavity (p < 0.05) and
      patients with the polymorphism presented less survival time (p < 0.05).
      CONCLUSIONS: We concluded that the CBS 844ins68 polymorphism is not associated
      with HNSCC risk and there is increased risk of this disease in male gender
      individuals smokers aged over 50 years. In adittion, the polymorphism is more
      frequent in patients with oral cavity as primary site and in patients with less
      survival time.

PMID- 22419939
TI  - Bipolar versus monopolar technique for palliative transurethral prostate
      resection.
AB  - INTRODUCTION: The aim was to evaluate the postoperative morbidity and outcome of
      palliative endoscopic resections for relief of infravesical obstruction in
      prostate cancer patients with hormone deprivation therapy, and to investigate the
      added value of bipolar technology over conventional monopolar resections.
      MATERIAL AND METHODS: A retrospective study was performed on 70 patients with
      prostate cancer under hormone deprivation therapy undergoing 75 endoscopic
      procedures, by either monopolar or bipolar technology, between August 2005 and
      March 2009 at a single institution. The analysis used outpatient, inpatient, and
      operative records, and observations of electrolyte changes in the serum,
      postoperative morbidity, and the overall results of palliative endoscopic
      resections. Preoperative cancer stages and grades were compared with the
      pathological findings after surgery. Postoperative outcome and complications of
      conventional monopolar and bipolar technology were compared. RESULTS: Over a
      period of 44 months, 34 conventional monopolar resections were performed in 32
      patients and 41 bipolar resections in 38 patients. Patients' profiles regarding
      age, initial cancer stage and grade, resection weight, resection speed,
      catheterization time, and hospital stay were similar in both groups. No
      statistically significant difference was observed in sodium drop (p = 0.802),
      clot retention (p = 0.565), or urinary retention (p = 0.292). The overall success
      rate in relieving obstruction leading to spontaneous voiding was 77%. While 38%
      of the patients had a high grade tumour at diagnosis, 79% were found to be high
      grade after the endoscopic resection (p < 0.0001). CONCLUSIONS: Palliative
      endoscopic transurethral resection is an acceptable and safe adjunctive surgical
      treatment for voiding disorders in prostate cancer patients. Bipolar technology
      offers no substantial benefit over conventional monopolar technology.

PMID- 22419940
TI  - The efficiency of a sedative or analgesic supplement to periprostatic nerve
      blockage for pain control during transrectal ultrasound-guided prostate biopsy -
      a prospective, randomized, controlled, double blind study.
AB  - INTRODUCTION: The aim was to examine the effect of a sedative or analgesic
      supplement to periprostatic nerve blockage (PNB) on pain reduction during probe
      insertion and needle penetration in patients undergoing transrectal ultrasound
      (TRUS)-guided prostate biopsy. We also investigated the effects of this procedure
      on the positive response rate in re-biopsy. MATERIAL AND METHODS: One hundred
      TRUS-guided prostate biopsy patients due to prostate-specific antigen (PSA)
      levels higher than 2.5 ng/ml and/or abnormal rectal examination findings were
      evaluated. Group 1 (PNB) was given periprostatic lidocaine injection before the
      procedure. Group 2 (analgesic) was given tramadol and PNB. Group 3 (sedative) was
      given midazolam and PNB. Group 4 (control) was not given any anaesthesia or
      analgesics. Pain scores were assessed during probe insertion and needle
      penetration by a visual analogue scale. RESULTS: During probe insertion, the mean
      pain score of the sedative group was lower than that of the control, analgesic
      and PNB groups (p < 0.001, p = 0.009, and p < 0.001, respectively). During needle
      penetration, the mean pain score of the control group was higher than that of the
      other groups (p < 0.001). The rate of positive response to re-biopsy was found to
      be 56% in the control group and between 92% and 100% in the other three groups (p
      < 0.001). CONCLUSION: According to our results, it can be concluded that
      midazolam, given supplementary to PNB, contributes as an effective and safe
      alternative for pain control during both probe insertion and penetration of the
      biopsy needle into the prostate capsule; however, tramadol supplement does not
      provide any additional contributions.

PMID- 22419941
TI  - Comparison of the effectiveness of compression stockings and layer compression
      systems in venous ulceration treatment.
AB  - INTRODUCTION: The aim of the research was to compare the dynamics of venous ulcer
      healing when treated with the use of compression stockings as well as original
      two- and four-layer bandage systems. MATERIAL AND METHODS: A group of 46 patients
      suffering from venous ulcers was studied. This group consisted of 36 (78.3%)
      women and 10 (21.70%) men aged between 41 and 88 years (the average age was 66.6
      years and the median was 67). Patients were randomized into three groups, for
      treatment with the ProGuide two-layer system, Profore four-layer compression, and
      with the use of compression stockings class II. In the case of multi-layer
      compression, compression ensuring 40 mmHg blood pressure at ankle level was used.
      RESULTS: In all patients, independently of the type of compression therapy, a few
      significant statistical changes of ulceration area in time were observed
      (Student's t test for matched pairs, p < 0.05). The largest loss of ulceration
      area in each of the successive measurements was observed in patients treated with
      the four-layer system - on average 0.63 cm2/per week. The smallest loss of
      ulceration area was observed in patients using compression stockings - on average
      0.44 cm(2)/per week. However, the observed differences were not statistically
      significant (Kruskal-Wallis test H = 4.45, p > 0.05). CONCLUSIONS: A systematic
      compression therapy, applied with preliminary blood pressure of 40 mmHg, is an
      effective method of conservative treatment of venous ulcers. Compression
      stockings and prepared systems of multi-layer compression were characterized by
      similar clinical effectiveness.

PMID- 22419942
TI  - Developmental dysplasia of the hip - angle trends after operation in different
      age groups.
AB  - INTRODUCTION: The aim of our study was to evaluate changes in collodiaphyseal,
      Hilgenreiner and Wiberg's centre-edge angle values in different age groups of
      children before and after surgical correction of developmental dysplasia of the
      hip. MATERIAL AND METHODS: We evaluated 78 children with developmental hip
      dysplasia treated at University Children's Hospital in Belgrade during a 10-year
      period. Three age groups were analysed: the first group younger than 24 months of
      life, the second group between 25 and 48 months, and the third group older than
      48 months of life. Three angles were evaluated separately before and after
      surgical correction: collodiaphyseal angle, Hilgenreiner angle and Wiberg's
      centre-edge angle. RESULTS: We found a highly statistically significant
      difference (p < 0.001) before and after the operation for collodiaphyseal and
      Hilgenreiner angle in the first and second age group, while there was a
      statistically significant difference (p < 0.05) in the third age group. Regarding
      Wiberg's centre-edge angle, there was a highly statistically significant
      difference (p < 0.001) in all age groups. One way ANOVA revealed a highly
      statistically significant difference (p < 0.001) for collodiaphyseal and
      Hilgenreiner angle in age groups before the operation, while after surgery such a
      trend remained for Hilgenreiner angle. Regarding collodiaphyseal and Wiberg's
      centre-edge angle in the period after correction, there was no statistical
      difference (p > 0.05) between age groups of the participants. CONCLUSIONS: Our
      findings demonstrate that age of participants is in correlation with correction
      of values for collodiaphyseal angle, Hilgenreiner angle and Wiberg's centre-edge
      angle in surgically treated children diagnosed with developmental dysplasia of
      the hip.

PMID- 22419944
TI  - Does the professional and working context of United Kingdom clinicians predict if
      they use practices to support patients with long term conditions to self manage?
AB  - INTRODUCTION: Our study examines how the professional and employment context may
      influence clinicians' practice self management support for patients with long
      term conditions (LTC). MATERIAL AND METHODS: We surveyed clinicians working with
      patients with depression, chronic obstructive pulmonary disorder (COPD), chronic
      musculo skeletal pain and diabetes. RESULTS: Clinicians most frequently endorsed
      items on a scale concerned with patient centeredness, and less frequently
      endorsed items concerned with clinical and organizational self management
      support. The most important factors predicting these latter activities were the
      intensity of working experience with patients with LTC and attending professional
      training addressing the principles and practice of self management support.
      Practicing patient centeredness was endorsed by nearly all respondents, and so
      was not sensitive to variation on work variables. CONCLUSIONS: The interaction of
      training and intensity of work with patients with LTC seems to have the most
      powerful effect on undertaking clinical and organizational self management
      support practices. To facilitate clinicians' practice of self management support
      for patients with LTC it is very important to provide relevant professional
      training and to build specialized patient care teams with professionals having
      complimentary skills.

PMID- 22419943
TI  - A survey on the distribution of healthy people with different anti-tumour
      ability.
AB  - INTRODUCTION: The aim of the study was to explore the distribution of healthy
      people with different anti-tumour ability. MATERIAL AND METHODS: Leukocytes were
      separated by the Ficoll-Hypaque density gradient centrifugal method. Then they
      were mixed with A549, MCF-7 and Hela cells at different ratios. The survival rate
      for target cells was observed and counted by Fluoroskan. Immune function for 200
      healthy people was analysed by flow cytometry. RESULTS: The results obtained by
      confocal microscopy revealed that human blood leukocytes possessed direct anti
      tumour activity. The survival rate for tumour cells was the lowest in the
      condition of 20:1 ratio of effector cells to target cells. We speculated that in
      200 healthy people the leukocyte capacity for killing MCF-7 cells is stronger
      than the leukocyte capacity for killing A549 cells and Hela cells. We also found
      that the distribution for 200 healthy people with different anti-tumour ability
      was different for different tumour cells. The number of healthy people with the
      strongest anti-tumour ability was highest when the target cells were MCF-7 cells.
      Moreover, the survival of A549, MCF-7 and Hela cells was correlated with T, B and
      NK lymphocytes. CONCLUSIONS: From the above, we can select healthy individuals
      with strong anti-tumour ability as anti-tumour donors according to their
      distribution with different anti-tumour ability, which opened up a new direction
      for fighting human cancer.

PMID- 22419945
TI  - The XmnI polymorphic site 5' to the gene G(gamma) in a Brazilian patient with
      sickle cell anaemia - fetal haemoglobin concentration, haematology and clinical
      features.
AB  - We report a 20-year-old female with sickle cell anaemia and with an HbF
      concentration of 15.8%. The patient was not using hydroxyurea and was not
      receiving regular blood transfusions. The patient never had chronic
      manifestations of sickle cell anaemia, only pain crises of a mild intensity.
      After laboratory tests, we found that she was homozygous for HbS with the
      Bantu/atypical haplotype, and was heterozygous for the XmnI site. The influence
      of the XmnI site on the expression of HbF can explain the amelioration in
      clinical features in this haplotype association in a case of sickle cell anaemia.

PMID- 22419947
TI  - Mesenteric angina through superior mesenteric venous thrombosis.
AB  - We present the case of a 67-year-old male with mesenteric venous thrombosis
      resulting in mesenteric angina, where early diagnosis made a favourable outcome
      possible through prompt anticoagulation and bowel rest. Mesenteric venous
      thrombosis is a relatively rare but important cause of bowel ischaemia, as a
      delay in diagnosis is associated with high morbidity and mortality. Early
      diagnosis through computed tomography scanning and subsequent treatment resulted
      in resolution of the thrombus with no long term sequelae.

PMID- 22419948
TI  - A 3 cm sealed pyloric perforation discovered during emergency cholecystectomy.
AB  - The diagnosis of acute cholecystitis is made on clinical, haematological,
      biochemical and radiological grounds, and laparoscopic cholecystectomy is
      commonly performed in the emergency setting. We report a case in which a patient
      diagnosed with acute cholecystitis was found to have a sealed pyloric perforation
      at laparoscopy as well as cholecystitis.

PMID- 22419946
TI  - Hyaluronic Acid-Based Hydrogels: from a Natural Polysaccharide to Complex
      Networks.
AB  - Hyaluronic acid (HA) is one of nature's most versatile and fascinating
      macromolecules. Being an essential component of the natural extracellular matrix
      (ECM), HA plays an important role in a variety of biological processes.
      Inherently biocompatible, biodegradable and non-immunogenic, HA is an attractive
      starting material for the construction of hydrogels with desired morphology,
      stiffness and bioactivity. While the interconnected network extends to the
      macroscopic level in HA bulk gels, HA hydrogel particles (HGPs, microgels or
      nanogels) confine the network to microscopic dimensions. Taking advantage of
      various scaffold fabrication techniques, HA hydrogels with complex architecture,
      unique anisotropy, tunable viscoelasticity and desired biologic outcomes have
      been synthesized and characterized. Physical entrapment and covalent integration
      of hydrogel particles in a secondary HA network give rise to hybrid networks that
      are hierarchically structured and mechanically robust, capable of mediating
      cellular activities through the spatial and temporal presentation of biological
      cues. This review highlights recent efforts in converting a naturally occurring
      polysaccharide to drug releasing hydrogel particles, and finally, complex and
      instructive macroscopic networks. HA-based hydrogels are promising materials for
      tissue repair and regeneration.

PMID- 22419949
TI  - Electrocardiograph abnormalities revealed during laparoscopy.
AB  - This brief case presents a well patient in whom an electrocardiograph abnormality
      consistent with an accessory pathway was found during a routine procedure. We
      present the electrocardiographs, explain the underlying condition, and consider
      why the abnormality was revealed in this manner.

PMID- 22419950
TI  - Idiopathic thrombocytopenic purpura associated with an astrocytoma.
AB  - We present the case of an 8-year-old girl with chronic idiopathic
      thrombocytopenic purpura (ITP) and a short history suggestive of raised
      intracranial pressure. Urgent computed tomography scan of the head showed a large
      bleed into a left cerebellar lesion. She underwent treatment with intravenous
      immunoglobulin (IVIg) and steroids to increase her platelet count, followed by
      excision of the lesion, which was found to be a benign pilocytic astrocytoma. The
      patient made a complete recovery and shortly afterwards underwent splenectomy,
      following which there was complete resolution of her thrombocytopenia.

PMID- 22419951
TI  - Koro-like symptoms in two Greek men.
AB  - Koro syndrome is a psychiatric disorder characterised, in its typical form, by
      acute and intense anxiety, with complaints in men of a shrinking penis or fear of
      its retraction into the abdomen and resultant death. Initially, this syndrome was
      described as a culture specific disorder. Sporadic cases referred to as the koro
      like syndrome have been observed in western countries recently. They are more
      likely to appear in the context of a psychiatric or neurological disorder. The
      clinical course of culture bound koro syndrome is usually self limited, but in
      some cases it can be transient or take on a chronic or recurrent form, lasting
      from days to weeks, months or even years. We present two cases, one of a middle
      aged man whose koro-like symptoms have persisted for over 18 years in a relapse
      mode that is rarely observed, and one of a young schizophrenic, who also exhibits
      koro-like symptoms.

PMID- 22419952
TI  - Ischaemic stroke in a patient on sunitinib.
AB  - Concerns have been raised about possible theoretical risk of thrombosis and
      bleeding with sunitinib (anti-vascular endothelial cell growth factor agent)
      therapy used for treatment of metastatic renal cell carcinoma. We present the
      first case of stroke in an older man with metastatic renal cell carcinoma, on
      sunitinib therapy.

PMID- 22419953
TI  - Warfarin, head injury and bruising.
AB  - A 75-year-old woman with a history of recurrent pulmonary emboli and atrial
      fibrillation presented with shortness of breath. Her warfarin had been stopped 4
      weeks previously after a minor fall where a head injury and extensive facial
      "bruising" was noted. A computed tomography pulmonary angiogram subsequently
      confirmed another pulmonary embolus. On examination the discolouration was still
      evident, but it was noted to be in a photosensitive distribution, and on further
      questioning it was determined that it had been present for some months before the
      fall. The patient had been on minocycline for acne rosacea for several years and
      the diagnosis of minocycline induced hyperpigmentation allowed for a more
      considered decision to restart warfarin.

PMID- 22419954
TI  - Cutaneous side effects of new antitumor drugs: clinical features and management.
AB  - BACKGROUND: Many new antitumor drugs have been approved in recent years. Their
      side-effect profiles are distinct from those of older drugs, and their adverse
      effects are sometimes highly specific, particularly with respect to the skin.
      METHODS: This article is based on articles retrieved by a selective search in
      Medline and the database of the American Society of Clinical Oncology (ASCO), as
      well as on the authors' personal experience. RESULTS: Cutaneous adverse effects
      are among the more common adverse effects of new antitumor drugs: they occur in
      up to 34% of patients receiving multikinase inhibitors, up to 90% of those
      receiving selective tyrosine kinase inhibitors (such as EGFR or mutant BRAF
      inhibitors), and up to 68% of those receiving immunotherapeutic agents (such as
      CTLA4 inhibitors). These adverse effects can be correlated with therapeutic
      benefit, but they can also be treatment-limiting because of their severity or
      visibility. CONCLUSION: The recognition and proper management of cutaneous
      adverse effects is an important part of treatment with new antitumor drugs.

PMID- 22419955
TI  - Medical ethical knowledge and moral attitudes among physicians in Bavaria.
AB  - BACKGROUND: Everyday clinical practice requires knowledge of medical ethics and
      the taking of moral positions. We investigated the ethical knowledge and
      attitudes of a representative sample of physicians with regard to end-of-life
      decisions, euthanasia, and the physician-patient relationship. METHODS: 192
      physicians (96 women, 96 men; mean age 50) in a random sample of Bavarian
      physicians completed our structured questionnaire. Data were collected from
      September to November 2010. RESULTS: There was much uncertainty among the
      respondents about the relevant knowledge for end-of-life decisions and the
      implementation of existing guidelines and laws on euthanasia and advance
      directives. Attitudes to ethical questions were found to be correlated with the
      length of time the physicians had been in practice. CONCLUSION: Physicians'
      personal values and moral attitudes play a major role in clinical decision
      making. We used a questionnaire to examine physicians' opinions about end-of-life
      issues and to determine the factors that might influence them. We found their
      knowledge of medical ethics to be inadequate. Competence in medical ethics needs
      to be strengthened by more ethical teaching in medical school, specialty
      training, and continuing medical education.

PMID- 22419956
TI  - Correspondence (letter to the editor): Avoid further transmission.

PMID- 22419957
TI  - Correspondence (letter to the editor): Poor-quality data.

PMID- 22419958
TI  - Correspondence (letter to the editor): Hand hygiene-other remedies are also
      effective.

PMID- 22419960
TI  - Correspondence (letter to the editor): Pansinusitis possible.

PMID- 22419961
TI  - Correspondence (reply): In Reply. Cluster headache.

PMID- 22419962
TI  - Consciousness and cognitive control.
AB  - The implementation or change of information processing routines, known as
      cognitive control, is traditionally believed to be closely linked to
      consciousness. It seems that we exert control over our behavior if we know the
      reasons for, and consequences of, doing so. Recent research suggests, however,
      that several behavioral phenomena that have been construed as instances of
      cognitive control can be prompted by events of which actors are not aware. Here
      we give a brief review of this research, discuss possible reasons for
      inconsistencies in the empirical evidence, and suggest some lines of future
      research. Specifically, we suggest to differentiate cognitive control evoked
      either because of explicit or because of implicit control cues. While the former
      type of control seems to work outside of awareness, the latter type of control
      seems to be restricted to consciously registered events that call for control.

PMID- 22419963
TI  - Time-course of hemispheric preference for processing contralateral relevant
      shapes: P1pc, N1pc, N2pc, N3pc.
AB  - A most sensitive and specific electrophysiological indicator of selective
      processing of visual stimuli is the N2pc component. N2pc is a negative EEG
      potential peaking 250 ms after stimulus onset, recorded from posterior sites
      contralateral to relevant stimuli. Additional deflections preceding or following
      N2pc have been obtained in previous studies, possibly produced by specific
      stimulus features or specific prime-target sequences. To clarify the entire time
      course of the contralateral- ipsilateral (C-I) difference recorded from the scalp
      above visual cortex in response to left-right pairs of targets and distracters, C
      I differences were here compared between two types of stimuli and between stimuli
      that were or were not preceded by masked neutral primes. The C-I difference
      waveform consisted of several peaks, termed here P1pc (60-100 ms after target
      onset), N1pc (120-160 ms), N2pc (220-280 ms), and N3pc (360-400 ms). Being
      markedly enhanced when stimuli were preceded by the neutral primes, P1pc may
      indicate a response to stimulus change. Also, when stimuli were primed, N2pc
      reached its peak earlier, thereby tending to merge with N1pc. N3pc seemed to
      increase when target discrimination was difficult. N1pc, N2pc, and N3pc appear as
      three periods of one process. N3pc probably corresponds to L400 or SPCN as
      described in other studies. These observations suggest that the
      neurophysiological basis of stimulus-driven focusing of attention on target
      stimuli is a process that lasts for hundreds of milliseconds, with the relevant
      hemisphere being activated in an oscillating manner as long as required by the
      task.

PMID- 22419964
TI  - Evidence for perceptual learning with repeated stimulation after partial and
      total cortical blindness.
AB  - Lesions of occipital cortex result in loss of sight in the corresponding regions
      of visual fields. The traditional view that, apart from some spontaneous recovery
      in the acute phase, field defects remain permanently and irreversibly blind, has
      been challenged. In patients with partial field loss, a range of residual visual
      abilities in the absence of conscious perception (blindsight) has been
      demonstrated (Weiskrantz, 1986). Recent findings (Sahraie et al., 2006, 2010)
      have also demonstrated increased visual sensitivity in the field defect following
      repeated stimulation. We aimed to extend these findings by systematically
      exploring whether repeated stimulation can also lead to increased visual
      sensitivity in two cases with total (bilateral) cortical blindness. In addition,
      for a case of partial blindness, we examined the extent of the recovery as a
      function of stimulated region of the visual field, over extended periods of
      visual training. Positive auditory feedback was provided during the training task
      for correct detection of a spatial grating pattern presented at specific
      retinotopic locations using a temporal two alternative forced-choice paradigm
      (Neuro-Eye Therapy). All three cases showed improved visual sensitivity with
      repeated stimulation. The findings indicate that perceptual learning can occur
      through systematic visual field stimulation even in cases of bilateral cortical
      blindness.

PMID- 22419965
TI  - Dissociating effects of subclinical anxiety and depression on cognitive control.
AB  - Even at subclinical levels, anxiety and depression are associated with impaired
      cognitive control. It is unclear, though, to what extent these deficits reflect a
      common underlying dysfunction. Using a non-affective hybrid masked prime-Simon
      task, we obtained several measures of within- and between- trial inhibitory
      behavioral control in 80 young, healthy volunteers, together with measures of
      their anxiety and depression levels. Neither depression nor anxiety affected low
      level within-trial control, or any of the between-trial control measures.
      However, increased levels of depression, but not of anxiety, were associated with
      impaired high-level within-trial control (increased Simon effect). Results
      indicate that depression, but not anxiety, impairs voluntary online response
      control mechanisms independent of affective content.

PMID- 22419966
TI  - Attentional sensitization of unconscious visual processing: Top-down influences
      on masked priming.
AB  - Classical theories of automaticity assume that automatic processes elicited by
      unconscious stimuli are autonomous and independent of higher-level cognitive
      influences. In contrast to these classical conceptions, we argue that automatic
      processing depends on attentional amplification of task-congruent processing
      pathways and propose an attentional sensitization model of unconscious visual
      processing: According to this model, unconscious visual processing is automatic
      in the sense that it is initiated without deliberate intention. However,
      unconscious visual processing is susceptible to attentional top-down control and
      is only elicited if the cognitive system is configured accordingly. In this
      article, we describe our attentional sensitization model and review recent
      evidence demonstrating attentional influences on subliminal priming, a
      prototypical example of an automatic process. We show that subliminal priming (a)
      depends on attentional resources, (b) is susceptible to stimulus expectations,
      (c) is influenced by action intentions, and (d) is modulated by task sets. These
      data suggest that attention enhances or attenuates unconscious visual processes
      in congruency with attentional task representations similar to conscious
      perception. We argue that seemingly paradoxical, hitherto unexplained findings
      regarding the automaticity of the underlying processes in many cognitive domains
      can be easily accommodated by our attentional sensitization model. We conclude
      this review with a discussion of future research questions regar-ding the nature
      of attentional control of unconscious visual processing.

PMID- 22419967
TI  - The influence of distracter and target features on distracter induced blindness.
AB  - The inhibitory effect of the processing of target-like distracters has already
      been shown to affect the conscious detection of simple motion and simple
      orientation stimuli in a random dot kinematogram. In two experiments we examined
      the effects of single-feature motion distracters, single-feature orientation
      distracters, and combined-feature distracters containing both motion and
      orientation information. The target was specified as a coherent motion episode
      (Experiment 1) or as a combined-feature episode where the coherent motion was
      accompanied by an abrupt change in line orientation (Experiment 2). Results
      showed that (a) the respective feature-specific inhibitory processes operate
      separately even when the distracter features are presented simultaneously and (b)
      both inhibitory processes contribute to the blindness effect when the conjunction
      of two features is defined as the target. Again, this inhibitory-process is
      feature-specific: Only features that are defined in the task are represented in
      the inhibitory task set. In case of combined- feature task-sets, these
      representations remain separate, so that combined-feature distracters as well as
      single-feature distracters are able to induce blindness effects.

PMID- 22419968
TI  - Nanoscale thermal probing.
AB  - Nanoscale novel devices have raised the demand for nanoscale thermal
      characterization that is critical for evaluating the device performance and
      durability. Achieving nanoscale spatial resolution and high accuracy in
      temperature measurement is very challenging due to the limitation of measurement
      pathways. In this review, we discuss four methodologies currently developed in
      nanoscale surface imaging and temperature measurement. To overcome the
      restriction of the conventional methods, the scanning thermal microscopy
      technique is widely used. From the perspective of measuring target, the optical
      feature size method can be applied by using either Raman or fluorescence
      thermometry. The near-field optical method that measures nanoscale temperature by
      focusing the optical field to a nano-sized region provides a non-contact and non
      destructive way for nanoscale thermal probing. Although the resistance
      thermometry based on nano-sized thermal sensors is possible for nanoscale thermal
      probing, significant effort is still needed to reduce the size of the current
      sensors by using advanced fabrication techniques. At the same time, the
      development of nanoscale imaging techniques, such as fluorescence imaging,
      provides a great potential solution to resolve the nanoscale thermal probing
      problem.

PMID- 22419969
TI  - Editorial.

PMID- 22419970
TI  - Differential and integral views of genetics in computational systems biology.
AB  - This article uses an integrative systems biological view of the relationship
      between genotypes and phenotypes to clarify some conceptual problems in
      biological debates about causality. The differential (gene-centric) view is
      incomplete in a sense analogous to using differentiation without integration in
      mathematics. Differences in genotype are frequently not reflected in significant
      differences in phenotype as they are buffered by networks of molecular
      interactions capable of substituting an alternative pathway to achieve a given
      phenotype characteristic when one pathway is removed. Those networks integrate
      the influences of many genes on each phenotype so that the effect of a
      modification in DNA depends on the context in which it occurs. Mathematical
      modelling of these interactions can help to understand the mechanisms of
      buffering and the contextual-dependence of phenotypic outcome, and so to
      represent correctly and quantitatively the relations between genomes and
      phenotypes. By incorporating all the causal factors in generating a phenotype,
      this approach also highlights the role of non-DNA forms of inheritance, and of
      the interactions at multiple levels.

PMID- 22419971
TI  - What it takes to understand and cure a living system: computational systems
      biology and a systems biology-driven pharmacokinetics-pharmacodynamics platform.
AB  - The utility of model repositories is discussed in the context of systems biology
      (SB). It is shown how such repositories, and in particular their live versions,
      can be used for computational SB: we calculate the robustness of the yeast
      glycolytic network with respect to perturbations of one of its enzyme activities
      and one transport system. The robustness with respect to perturbations in the key
      enzyme phosphofructokinase is surprisingly large. We then note the upcoming
      convergence of pharmacokinetics-pharmacodynamics (PK-PD) and bottom-up SB. In PK
      alone, quite a few one-, two- or more compartment models provide valuable initial
      guesses and insights into the absorption, distribution, metabolism and excretion
      of particular drugs. These models are phenomenological however, forbidding
      implementation of molecule-based tools and network information. In order to
      facilitate a fruitful synergy between SB and PK-PD, and between PK and PD, we
      present a new platform that combines standard phenomenological models used in the
      PK/PD field with mechanism-based SB models and approaches.

PMID- 22419972
TI  - A skeleton model for the network of cyclin-dependent kinases driving the
      mammalian cell cycle.
AB  - We previously proposed a detailed, 39-variable model for the network of cyclin
      dependent kinases (Cdks) that controls progression along the successive phases of
      the mammalian cell cycle. Here, we propose a skeleton, 5-variable model for the
      Cdk network that can be seen as the backbone of the more detailed model for the
      mammalian cell cycle. In the presence of sufficient amounts of growth factor, the
      skeleton model also passes from a stable steady state to sustained oscillations
      of the various cyclin/Cdk complexes. This transition corresponds to the switch
      from quiescence to cell proliferation. Sequential activation of the cyclin/Cdk
      complexes allows the ordered progression along the G1, S, G2 and M phases of the
      cell cycle. The 5-variable model can also account for the existence of a
      restriction point in G1, and for endoreplication. Like the detailed model, it
      contains multiple oscillatory circuits and can display complex oscillatory
      behaviour such as quasi-periodic oscillations and chaos. We compare the dynamical
      properties of the skeleton model with those of the more detailed model for the
      mammalian cell cycle.

PMID- 22419973
TI  - An automaton model for the cell cycle.
AB  - WE CONSIDER AN AUTOMATON MODEL THAT PROGRESSES SPONTANEOUSLY THROUGH THE FOUR
      SUCCESSIVE PHASES OF THE CELL CYCLE: G1, S (DNA replication), G2 and M (mitosis).
      Each phase is characterized by a mean duration tau and a variability V. As soon
      as the prescribed duration of a given phase has passed, the transition to the
      next phase of the cell cycle occurs. The time at which the transition takes place
      varies in a random manner according to a distribution of durations of the cell
      cycle phases. Upon completion of the M phase, the cell divides into two cells,
      which immediately enter a new cycle in G1. The duration of each phase is
      reinitialized for the two newborn cells. At each time step in any phase of the
      cycle, the cell has a certain probability to be marked for exiting the cycle and
      dying at the nearest G1/S or G2/M transition. To allow for homeostasis, which
      corresponds to maintenance of the total cell number, we assume that cell death
      counterbalances cell replication at mitosis. In studying the dynamics of this
      automaton model, we examine the effect of factors such as the mean durations of
      the cell cycle phases and their variability, the type of distribution of the
      durations, the number of cells, the regulation of the cell population size and
      the independence of steady-state proportions of cells in each phase with respect
      to initial conditions. We apply the stochastic automaton model for the cell cycle
      to the progressive desynchronization of cell populations and to their entrainment
      by the circadian clock. A simple deterministic model leads to the same steady
      state proportions of cells in the four phases of the cell cycle.

PMID- 22419974
TI  - Model-driven therapeutic treatment of neurological disorders: reshaping brain
      rhythms with neuromodulation.
AB  - Electric stimulation has been investigated for several decades to treat, with
      various degrees of success, a broad spectrum of neurological disorders.
      Historically, the development of these methods has been largely empirical but has
      led to a remarkably efficient, yet invasive treatment: deep brain stimulation
      (DBS). However, the efficiency of DBS is limited by our lack of understanding of
      the underlying physiological mechanisms and by the complex relationship existing
      between brain processing and behaviour. Biophysical modelling of brain activity,
      describing multi-scale spatio-temporal patterns of neuronal activity using a
      mathematical model and taking into account the physical properties of brain
      tissue, represents one way to fill this gap. In this review, we illustrate how
      biophysical modelling is beginning to emerge as a driving force orienting the
      development of innovative brain stimulation methods that may move DBS forward. We
      present examples of modelling works that have provided fruitful insights in
      regards to DBS underlying mechanisms, and others that also suggest potential
      improvements for this neurosurgical procedure. The reviewed literature emphasizes
      that biophysical modelling is a valuable tool to assist a rational development of
      electrical and/or magnetic brain stimulation methods tailored to both the disease
      and the patient's characteristics.

PMID- 22419975
TI  - Multi-frequency activation of neuronal networks by coordinated reset stimulation.
AB  - We computationally study whether it is possible to stimulate a neuronal
      population in such a way that its mean firing rate increases without an increase
      of the population's net synchronization. For this, we use coordinated reset (CR)
      stimulation, which has previously been developed to desynchronize populations of
      oscillatory neurons. Intriguingly, delivered to a population of predominantly
      silent FitzHugh-Nagumo or Hindmarsh-Rose neurons at sufficient stimulation
      amplitudes, CR robustly causes a multi-frequency activation: different Arnold
      tongues such as 1 : 1 or n : m entrained neuronal clusters emerge, which consist
      of phase-shifted sub clusters. Owing to the clustering pattern the neurons'
      timing is well balanced, so that in total there is no synchronization. Our
      findings may contribute to the development of novel and safe stimulation
      treatments that specifically counteract cerebral hypo-activity without promoting
      pathological synchronization or inducing epileptic seizures.

PMID- 22419976
TI  - Excitation block in a nerve fibre model owing to potassium-dependent changes in
      myelin resistance.
AB  - The myelinated nerve fibre is formed by an axon and Schwann cells or
      oligodendrocytes that sheath the axon by winding around it in tight myelin
      layers. Repetitive stimulation of a fibre is known to result in accumulation of
      extracellular potassium ions, especially between the axon and the myelin. Uptake
      of potassium leads to Schwann cell swelling and myelin restructuring that impacts
      the electrical properties of the myelin. In order to further understand the
      dynamic interaction that takes place between the myelin and the axon, we have
      modelled submyelin potassium accumulation and related changes in myelin
      resistance during prolonged high-frequency stimulation. We predict that potassium
      mediated decrease in myelin resistance leads to a functional excitation block
      with various patterns of altered spike trains. The patterns are found to depend
      on stimulation frequency and amplitude and to range from no block (less than 100
      Hz) to a complete block (greater than 500 Hz). The transitional patterns include
      intermittent periodic block with interleaved spiking and non-spiking intervals of
      different relative duration as well as an unstable regime with chaotic switching
      between the spiking and non-spiking states. Intermittent conduction blocks are
      accompanied by oscillations of extracellular potassium. The mechanism of
      conductance block based on myelin restructuring complements the already known and
      modelled block via hyperpolarization mediated by the axonal sodium pump and
      potassium depolarization.

PMID- 22419978
TI  - Significance of microvascular remodelling for the vascular flow reserve in
      hypertension.
AB  - Vascular flow reserve (VFR) is the relative increase in tissue perfusion from the
      resting state to a state with maximum vasodilatation. Longstanding hypertension
      reduces the VFR, which in turn reduces the maximum working capacity of the
      tissue. In principle, both inward arteriolar remodelling and rarefaction of the
      microvascular network may contribute to this reduction. These processes are known
      to occur simultaneously in the microcirculation of the hypertensive individual
      and both cause a reduction in the luminal trans-sectional area available for
      perfusion. Which of them is the main factor responsible for the reduction in VFR
      is, however, not known. Here we present simulations performed on large
      microvascular networks to assess the VFR in various situations. Particular
      attention is paid to the VFR in networks in which the vessels have structurally
      adapted to a sustained increase in pressure by inward eutrophic remodelling
      (IER), i.e. by redistributing the same amount of wall material around a smaller
      lumen. Collectively, the results indicate that the IER may not per se be the main
      factor responsible for the hypertensive reduction in VFR. Rather, it may be
      explained by the presence of arteriolar and capillary rarefaction.

PMID- 22419977
TI  - Construction and validation of anisotropic and orthotropic ventricular geometries
      for quantitative predictive cardiac electrophysiology.
AB  - Reaction-diffusion computational models of cardiac electrophysiology require both
      dynamic excitation models that reconstruct the action potentials of myocytes as
      well as datasets of cardiac geometry and architecture that provide the electrical
      diffusion tensor D, which determines how excitation spreads through the tissue.
      We illustrate an experimental pipeline we have developed in our laboratories for
      constructing and validating such datasets. The tensor D changes with location in
      the myocardium, and is determined by tissue architecture. Diffusion tensor
      magnetic resonance imaging (DT-MRI) provides three eigenvectors e(i) and
      eigenvalues lambda(i) at each voxel throughout the tissue that can be used to
      reconstruct this architecture. The primary eigenvector e(1) is a histologically
      validated measure of myocyte orientation (responsible for anisotropic
      propagation). The secondary and tertiary eigenvectors (e(2) and e(3)) specify the
      directions of any orthotropic structure if lambda(2) is significantly greater
      than lambda(3)-this orthotropy has been identified with sheets or cleavage
      planes. For simulations, the components of D are scaled in the fibre and cross
      fibre directions for anisotropic simulations (or fibre, sheet and sheet normal
      directions for orthotropic tissues) so that simulated conduction velocities match
      values from optical imaging or plunge electrode experiments. The simulated
      pattern of propagation of action potentials in the models is partially validated
      by optical recordings of spatio-temporal activity on the surfaces of hearts. We
      also describe several techniques that enhance components of the pipeline, or that
      allow the pipeline to be applied to different areas of research: Q ball imaging
      provides evidence for multi-modal orientation distributions within a fraction of
      voxels, infarcts can be identified by changes in the anisotropic structure
      irregularity in myocyte orientation and a decrease in fractional anisotropy,
      clinical imaging provides human ventricular geometry and can identify ischaemic
      and infarcted regions, and simulations in human geometries examine the roles of
      anisotropic and orthotropic architecture in the initiation of arrhythmias.

PMID- 22419979
TI  - C-type period-doubling transition in nephron autoregulation.
AB  - The functional units of the kidney, called nephrons, utilize mechanisms that
      allow the individual nephron to regulate the incoming blood flow in response to
      fluctuations in the arterial pressure. This regulation tends to be unstable and
      to generate self-sustained oscillations, period-doubling bifurcations, mode
      locking and other nonlinear dynamic phenomena in the tubular pressures and flows.
      Using a simplified nephron model, the paper examines how the regulatory
      mechanisms react to an external periodic variation in arterial pressure near a
      region of resonance with one of the internally generated mode-locked cycles. We
      show how the stable and unstable resonance cycles generated in this response
      undergo interconnected cascades of period-doubling bifurcations and how each
      period doubling leads to the formation of a new pair of saddle-node bifurcation
      curves along the edges of the resonance zone. We also show how period doubling of
      the resonance cycles is accompanied by a torus-doubling process in the
      quasiperiodic regime that exists outside of the resonance zone.

PMID- 22419980
TI  - Exocytosis from pancreatic beta-cells: mathematical modelling of the exit of low
      molecular-weight granule content.
AB  - Pancreatic beta-cells use Ca(2+)-dependent exocytosis of large dense core
      vesicles to release insulin. Exocytosis in beta-cells has been studied
      biochemically, biophysically and optically. We have previously developed a
      biophysical method to monitor release of endogenous intragranular constituents
      that are co-released with insulin. This technique involves the expression of
      ionotropic membrane receptors in the beta-cell plasma membrane and enables
      measurements of exocytosis of individual vesicles with sub-millisecond
      resolution. Like carbon fibre amperometry, this method allows fine details of the
      release process, like the expansion of the fusion pore (the narrow connection
      between the granule lumen and the extracellular space), to be monitored. Here, we
      discuss experimental data obtained with this method within the framework of a
      simple mathematical model that describes the release of low-molecular
      constituents during exocytosis of the insulin granules. Our findings suggest that
      the fusion pore functions as a molecular sieve, allowing differential release of
      low- and high-molecular-weight granule constituents.

PMID- 22419981
TI  - Circadian desynchronization.
AB  - The suprachiasmatic nucleus (SCN) coordinates via multiple outputs physiological
      and behavioural circadian rhythms. The SCN is composed of a heterogeneous network
      of coupled oscillators that entrain to the daily light-dark cycles. Outside the
      physiological entrainment range, rich locomotor patterns of desynchronized
      rhythms are observed. Previous studies interpreted these results as the output of
      different SCN neural subpopulations. We find, however, that even a single
      periodically driven oscillator can induce such complex desynchronized locomotor
      patterns. Using signal analysis, we show how the observed patterns can be
      consistently clustered into two generic oscillatory interaction groups:
      modulation and superposition. In seven of 17 rats undergoing forced
      desynchronization, we find a theoretically predicted third spectral component.
      Combining signal analysis with the theory of coupled oscillators, we provide a
      framework for the study of circadian desynchronization.

PMID- 22419982
TI  - Synchronization and entrainment of coupled circadian oscillators.
AB  - Circadian rhythms in mammals are controlled by the neurons located in the
      suprachiasmatic nucleus of the hypothalamus. In physiological conditions, the
      system of neurons is very efficiently entrained by the 24 h light-dark cycle.
      Most of the studies carried out so far emphasize the crucial role of the
      periodicity imposed by the light-dark cycle in neuronal synchronization.
      Nevertheless, heterogeneity as a natural and permanent ingredient of these
      cellular interactions seemingly plays a major role in these biochemical
      processes. In this paper, we use a model that considers the neurons of the
      suprachiasmatic nucleus as chemically coupled modified Goodwin oscillators, and
      introduce non-negligible heterogeneity in the periods of all neurons in the form
      of quenched noise. The system response to the light-dark cycle periodicity is
      studied as a function of the interneuronal coupling strength, external forcing
      amplitude and neuronal heterogeneity. Our results indicate that the right amount
      of heterogeneity helps the extended system to respond globally in a more coherent
      way to the external forcing. Our proposed mechanism for neuronal synchronization
      under external periodic forcing is based on heterogeneity-induced oscillator
      death, damped oscillators being more entrainable by the external forcing than the
      self-oscillating neurons with different periods.

PMID- 22419983
TI  - Balance equations can buffer noisy and sustained environmental perturbations of
      circadian clocks.
AB  - We present a new approach to understanding how regulatory networks such as
      circadian clocks might evolve robustness to environmental fluctuations. The
      approach is in terms of new balance equations that we derive. We use it to
      describe how an entrained clock can buffer the effects of daily fluctuations in
      light and temperature levels. We also use it to study a different approach to
      temperature compensation where instead of considering a free-running clock, we
      study temperature buffering of the phases in a light-entrained clock, which we
      believe is a more physiological setting.

PMID- 22419984
TI  - A global conversation about energy from biomass: the continental conventions of
      the global sustainable bioenergy project.
AB  - The global sustainable bioenergy (GSB) project was formed in 2009 with the goal
      of providing guidance with respect to the feasibility and desirability of
      sustainable, bioenergy-intensive futures. Stage 1 of this project held
      conventions with a largely common format on each of the world's continents, was
      completed in 2010, and is described in this paper. Attended by over 400 persons,
      the five continental conventions featured presentations, breakout sessions, and
      drafting of resolutions that were unanimously passed by attendees. The
      resolutions highlight the potential of bioenergy to make a large energy supply
      contribution while honouring other priorities, acknowledge the breadth and
      complexity of bioenergy applications as well as the need to take a systemic
      approach, and attest to substantial intra- and inter-continental diversity with
      respect to needs, opportunities, constraints and current practice relevant to
      bioenergy. The following interim recommendations based on stage 1 GSB activities
      are offered: - Realize that it may be more productive, and also more correct, to
      view the seemingly divergent assessments of bioenergy as answers to two different
      questions rather than the same question. Viewed in this light, there is
      considerably more scope for reconciliation than might first be apparent, and it
      is possible to be informed rather than paralysed by divergent assessments.-
      Develop established and advanced bioenergy technologies such that each
      contributes to the other's success. That is, support and deploy in the near-term
      meritorious, established technologies in ways that enhance rather than impede
      deployment of advanced technologies, and support and deploy advanced technologies
      in ways that expand rather than contract opportunities for early adopters and
      investors.- Be clear in formulating policies what mix of objectives are being
      targeted, measure the results of these policies against these objectives and
      beware of unintended consequences.- Undertake further exploration of land
      efficiency levers and visions for multiply-beneficial bioenergy deployment. This
      should be unconstrained by current practices, since we cannot hope to achieve a
      sustainable and a secure future by continuing the practices that have led to the
      unsustainable and insecure present. It should also be approached from a global
      perspective, based on the best science available, and consider the diverse
      realities, constraints, needs and opportunities extant in different regions of
      the world.The future trajectory of the GSB project is also briefly considered.

PMID- 22419985
TI  - Modelling of pH dynamics in brain cells after stroke.
AB  - The identification of salvageable brain tissue is a major challenge at stroke
      presentation. Standard techniques used in this context, such as the perfusion
      diffusion mismatch, remain controversial. There is thus a need for new methods to
      help guide treatment. The potential role of pH imaging in this context is
      currently being investigated. Intracellular pH varies as a function of local
      perfusion, intracellular energy stores and time. Low pH triggers the production
      of free radicals and affects the calcium balance of the cells, which may lead to
      apoptosis and cell death. Thus, the characterization of pH dynamics may have
      predictive value for cell death after stroke, particularly when combined with
      novel imaging techniques. Therefore, we have extended an existing model of brain
      cellular metabolism to simulate the pH response of cells to ischaemia. Simulation
      results for conditions of reduced cerebral blood flow show good agreement for the
      evolution of intracellular pH with previously reported measurements and encourage
      the development of quantitative pH imaging to validate the predictive value of
      pH.

PMID- 22419987
TI  - A Bayesian model for the common effects of multiple predictors on mixed outcomes.
AB  - We propose a Bayesian multivariate model in which a single linear combination of
      the covariates predict multiple outcomes simultaneously. The single linear
      combination is a data-derived score along the lines of the Apache or Charlson
      index scores for critically ill patients, the Karnofsky or Eastern Cooperative
      Oncology Group score for cancer patients or Euro-score for cardiac patients that
      may be used to predict multiple outcomes. Outcomes may be discrete or continuous
      and we use a composition of generalized linear models for the marginal
      distribution for each outcome. We explain how to set the prior distribution and
      we use Markov chain Monte Carlo methods to calculate the posterior distribution.
      We propose two types of expanded models to diagnose whether each outcome indeed
      has predictor effects common with the other outcomes, and whether a particular
      predictor is commonly predictive for all outcomes. We determine a final model
      based on the diagnostic models. The method is applied to a study yielding
      multiple psychometric outcomes of mixed type measured in young people living with
      human immunodeficiency virus.

PMID- 22419986
TI  - Acoustic radiation force-based elasticity imaging methods.
AB  - Conventional diagnostic ultrasound images portray differences in the acoustic
      properties of soft tissues, whereas ultrasound-based elasticity images portray
      differences in the elastic properties of soft tissues (i.e. stiffness,
      viscosity). The benefit of elasticity imaging lies in the fact that many soft
      tissues can share similar ultrasonic echogenicities, but may have different
      mechanical properties that can be used to clearly visualize normal anatomy and
      delineate pathological lesions. Acoustic radiation force-based elasticity imaging
      methods use acoustic radiation force to transiently deform soft tissues, and the
      dynamic displacement response of those tissues is measured ultrasonically and is
      used to estimate the tissue's mechanical properties. Both qualitative images and
      quantitative elasticity metrics can be reconstructed from these measured data,
      providing complimentary information to both diagnose and longitudinally monitor
      disease progression. Recently, acoustic radiation force-based elasticity imaging
      techniques have moved from the laboratory to the clinical setting, where
      clinicians are beginning to characterize tissue stiffness as a diagnostic metric,
      and commercial implementations of radiation force-based ultrasonic elasticity
      imaging are beginning to appear on the commercial market. This article provides
      an overview of acoustic radiation force-based elasticity imaging, including a
      review of the relevant soft tissue material properties, a review of radiation
      force-based methods that have been proposed for elasticity imaging, and a
      discussion of current research and commercial realizations of radiation force
      based-elasticity imaging technologies.

PMID- 22419988
TI  - The epigenome and top-down causation.
AB  - Genes store heritable information, but actual gene expression often depends on
      many so-called epigenetic factors, both physical and chemical, external to DNA.
      Epigenetic changes can be both reversible and heritable. The genome is associated
      with a physical object (DNA) with a specific location, whereas the epigenome is a
      global, systemic, entity. Furthermore, genomic information is tied to specific
      coded molecular sequences stored in DNA. Although epigenomic information can be
      associated with certain non-DNA molecular sequences, it is mostly not. Therefore,
      there does not seem to be a stored 'epigenetic programme' in the information
      theoretic sense. Instead, epigenomic control is-to a large extent-an emergent
      self-organizing phenomenon, and the real-time operation of the epigenetic
      'project' lies in the realm of nonlinear bifurcations, interlocking feedback
      loops, distributed networks, top-down causation and other concepts familiar from
      the complex systems theory. Lying at the heart of vital eukaryotic processes are
      chromatin structure, organization and dynamics. Epigenetics provides striking
      examples of how bottom-up genetic and top-down epigenetic causation intermingle.
      The fundamental question then arises of how causal efficacy should be attributed
      to biological information. A proposal is made to implement explicit downward
      causation by coupling information directly to the dynamics of chromatin, thus
      permitting the coevolution of dynamical laws and states, and opening up a new
      sector of dynamical systems theory that promises to display rich self-organizing
      and self-complexifying behaviour.

PMID- 22419989
TI  - Can clade age alone explain the relationship between body size and diversity?
AB  - One of the most striking patterns observed among animals is that smaller-bodied
      taxa are generally much more diverse than larger-bodied taxa. This observation
      seems to be explained by the mere fact that smaller-bodied taxa tend to have an
      older evolutionary origin and have therefore had more time to diversify. A few
      studies, based on the prevailing null model of diversification (i.e. the
      stochastic constant-rate birth-death model), have suggested that this is indeed
      the correct explanation, and body-size dependence of speciation and extinction
      rates does not play a role. However, there are several potential shortcomings to
      these studies: a suboptimal statistical procedure and a relatively narrow range
      of body sizes in the analysed data. Here, we present a more coherent statistical
      approach, maximizing the likelihood of the constant-rate birth-death model with
      allometric scaling of speciation and extinction rates, given data on extant
      diversity, clade age and average body size in each clade. We applied our method
      to a dataset compiled from the literature that includes a wide range of Metazoan
      taxa (range from midges to elephants). We find that the higher diversity among
      small animals is indeed, partly, caused by higher clade age. However, it is also
      partly caused by the body-size dependence of speciation and extinction rates. We
      find that both the speciation rate and extinction rate decrease with body size
      such that the net diversification rate is close to 0. Even more interestingly,
      the allometric scaling exponent of speciation and extinction rates is
      approximately -0.25, which implies that the per generation speciation and
      extinction rates are independent of body size. This suggests that the observed
      relationship between diversity and body size pattern can be explained by clade
      age alone, but only if clade age is measured in generations rather than years.
      Thus, we argue that the most parsimonious explanation for the observation that
      smaller-bodied taxa are more diverse is that their evolutionary clock ticks
      faster.

PMID- 22419990
TI  - How linear features alter predator movement and the functional response.
AB  - In areas of oil and gas exploration, seismic lines have been reported to alter
      the movement patterns of wolves (Canis lupus). We developed a mechanistic first
      passage time model, based on an anisotropic elliptic partial differential
      equation, and used this to explore how wolf movement responses to seismic lines
      influence the encounter rate of the wolves with their prey. The model was
      parametrized using 5 min GPS location data. These data showed that wolves
      travelled faster on seismic lines and had a higher probability of staying on a
      seismic line once they were on it. We simulated wolf movement on a range of
      seismic line densities and drew implications for the rate of predator-prey
      interactions as described by the functional response. The functional response
      exhibited a more than linear increase with respect to prey density (type III) as
      well as interactions with seismic line density. Encounter rates were
      significantly higher in landscapes with high seismic line density and were most
      pronounced at low prey densities. This suggests that prey at low population
      densities are at higher risk in environments with a high seismic line density
      unless they learn to avoid them.

PMID- 22419991
TI  - Revisiting detrended fluctuation analysis.
AB  - Half a century ago Hurst introduced Rescaled Range (R/S) Analysis to study
      fluctuations in time series. Thousands of works have investigated or applied the
      original methodology and similar techniques, with Detrended Fluctuation Analysis
      becoming preferred due to its purported ability to mitigate nonstationaries. We
      show Detrended Fluctuation Analysis introduces artifacts for nonlinear trends, in
      contrast to common expectation, and demonstrate that the empirically observed
      curvature induced is a serious finite-size effect which will always be present.
      Explicit detrending followed by measurement of the diffusional spread of a
      signals' associated random walk is preferable, a surprising conclusion given that
      Detrended Fluctuation Analysis was crafted specifically to replace this approach.
      The implications are simple yet sweeping: there is no compelling reason to apply
      Detrended Fluctuation Analysis as it 1) introduces uncontrolled bias; 2) is
      computationally more expensive than the unbiased estimator; and 3) cannot provide
      generic or useful protection against nonstationaries.

PMID- 22419992
TI  - A novel method for simultaneous analysis of three beta2-agonists in foods with
      the use of a gold-nanoparticle modified glassy carbon electrode and chemometrics.
AB  - An electrochemical method involving a gold nanoparticle modified glassy carbon
      electrode (AuNPs/GCE) was researched and developed for the simultaneous analysis
      of three beta(2)-agonists, ractopamine (RAC), salbutamol (SAL) and clenbuterol
      (CLB). The three analytes were electrocatalytically oxidized at the AuNP/GCE,
      which enhanced the oxidation peak current and influenced the shift of the
      oxidation potentials to lower values in comparison with the analysis involving
      only the GCE. The differential pulse stripping voltammetry (DPSV) voltammograms
      from the drug mixture produced complex, overlapping profiles, and chemometrics
      methods were applied for calibration modeling. The peak currents associated with
      RAC, SAL and CLB measurements were linear as a function of their concentrations
      (ranges within 0.005-0.150 MUg mL(-1)); the detection limits for RAC, SAL and CLB
      were 2.4, 5.8 and 2.6 ng mL(-1), respectively. It was shown that satisfactory
      quantitative results were obtained with the use of the MVC1 package of
      chemometrics methods e.g. the PLS1 calibration model produced a relative
      prediction error (RPE(T)) of 7.0% and an average recovery of 97.6%. The above
      AuNP/GCE was successfully employed for the simultaneous analysis of RAC, SAL and
      CLB in pork meat, liver and pig feed samples.

PMID- 22419993
TI  - In situ fabrication of metal-organic hybrid gels in a capillary for online
      enrichment of trace analytes in aqueous samples.
AB  - In this work we demonstrated a facile method for in situ fabrication of the
      Fe(3+)-1,3,5-benzenetricarboxylic acid (BTC) metal-organic coordination polymer
      gel in a capillary, which was efficiently applied to the online enrichment of
      trace polycyclic aromatic hydrocarbons (PAHs) in environmental water and
      amphetamines drugs in urine.

PMID- 22419994
TI  - Quadruply bonded dimolybdenum complexes with highly unusual geometries and vacant
      coordination sites.
AB  - New quadruply bonded dimolybdenum complexes of the terphenyl ligand Ar(Xyl(2))
      (Ar(Xyl(2)) = C(6)H(3)-2,6-(C(6)H(3)-2,6-Me(2))(2)) have been prepared and
      structurally characterized. The steric hindrance exerted by the Ar(Xyl(2)) groups
      causes the Mo atoms to feature unsaturated four-coordinate structures and a
      formal fourteen-electron count.

PMID- 22419995
TI  - Biphasic synovial sarcoma arising from superior vena cava.

PMID- 22419996
TI  - Intraoperative device closure of multidefect under transoesophageal
      echocardiographic guidance in an infant.

PMID- 22419997
TI  - Multidetector computed tomographic findings of an unroofed coronary sinus.

PMID- 22419998
TI  - Improving communication.

PMID- 22420000
TI  - Towards evidence-based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 1: Comparison of topical anaesthetic agents for minor wound
      closure in children.
AB  - A short-cut review was carried out to establish whether lignocaine, epinephrine,
      tetracaine gel is more effective than tetracaine, epinephrine, cocaine gel as a
      topical anaesthetic agent in minor skin lacerations that still need suturing.
      Three studies were directly relevant to the question. The author, date and
      country of publication, patient group studied, study type, relevant outcomes,
      results and study weaknesses of these papers are tabulated. The clinical bottom
      line is that lignocaine, epinephrine, tetracaine gel is as effective and is
      without the inherent disadvantages associated with cocaine.

PMID- 22420001
TI  - Towards evidence-based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 2: Treatment of Bell's palsy: should antiviral agents be added to
      prednisolone?
AB  - A short-cut review was carried out to establish whether Bell's palsy is best
      treated with a combination of prednisolone and an antiviral agent or prednisolone
      alone. Four systematic reviews and two small studies were directly relevant to
      the question. The author, date and country of publication, patient group studied,
      study type, relevant outcomes, results and study weaknesses of these papers are
      tabulated. The clinical bottom line is that there is insufficient evidence to
      recommend an antiviral agent in addition to prednisolone in the treatment of
      Bell's palsy.

PMID- 22420002
TI  - Towards evidence-based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 3: In a penetrating chest wound is a three-sided dressing or a one
      way chest seal better at preventing respiratory complications?
AB  - A short-cut review was carried out to establish whether the traditional three
      sided dressing is better than a one-way chest seal at preventing the respiratory
      complications from penetrating chest trauma. Only one animal study, two
      guidelines and two case reports provided published evidence relevant to the
      question. The author, date and country of publication, patient group studied,
      study type, relevant outcomes, results and study weaknesses of these papers are
      tabulated. The clinical bottom line is that there is very little evidence, but
      that the one-way seals may have practical advantages, particularly in the out-of
      hospital setting.

PMID- 22420004
TI  - AIP expression in sporadic somatotropinomas is a predictor of the response to
      octreotide LAR therapy independent of SSTR2 expression.

PMID- 22420005
TI  - Insulin and its analogues and their affinities for the IGF1 receptor.
AB  - Insulin analogues have been developed in an attempt to achieve a more
      physiological replacement of insulin and thereby a better glycaemic control.
      However, structural modification of the insulin molecule may result in altered
      binding affinities and activities to the IGF1 receptor (IGF1R). As a consequence,
      insulin analogues may theoretically have an increased mitogenic action compared
      to human insulin. In view of the lifelong exposure and large patient populations
      involved, insulin analogues with an increased mitogenic effect in comparison to
      human insulin may potentially constitute a major health problem, since these
      analogues may possibly induce the growth of pre-existing neoplasms. This
      hypothesis has been evaluated extensively in vitro and also in vivo by using
      animal models. In vitro, all at present commercially available insulin analogues
      have lower affinities for the insulin receptor (IR). Although it has been
      suggested that especially insulin analogues with an increased affinity for the
      IGF1R (such as insulin glargine) are more mitogenic when tested in vitro in cells
      expressing a high proportion of IGF1R, the question remains whether this has any
      clinical consequences. At present, there are several uncertainties which make it
      very difficult to answer this question decisively. In addition, recent data
      suggest that insulin (or insulin analogues)-mediated stimulation of IRs may play
      a key role in the progression of human cancer. More detailed information is
      required to elucidate the exact mechanisms as to how insulin analogues may
      activate the IR and IGF1R and how this activation may be linked to mitogenesis.

PMID- 22420006
TI  - MicroRNA expression profiling of carcinoma in situ cells of the testis.
AB  - Testicular germ cell tumours, seminoma (SE) and non-seminoma (NS), of young adult
      men develop from a precursor cell, carcinoma in situ (CIS), which resembles
      foetal gonocytes and retains embryonic pluripotency. We used microarrays to
      analyse microRNA (miRNA) expression in 12 human testis samples with CIS cells and
      compared it with miRNA expression profiles of normal adult testis, testis with
      Sertoli-cell-only that lacks germ cells, testis tumours (SE and embryonal
      carcinoma (EC), an undifferentiated component of NS) and foetal male and female
      gonads. Principal components analysis revealed distinct miRNA expression profiles
      characteristic for each of the different tissue types. We identified several
      miRNAs that were unique to testis with CIS cells, foetal gonads and testis
      tumours. These included miRNAs from the hsa-miR-371-373 and -302-367 clusters
      that have previously been reported in germ cell tumours and three miRNAs (hsa-miR
      96, -141 and -200c) that were also expressed in human epididymis. We found
      several miRNAs that were upregulated in testis tumours: hsa-miR-9, -105 and -182
      183-96 clusters were highly expressed in SE, while the hsa-miR-515-526 cluster
      was high in EC. We conclude that the miRNA expression profile changes during
      testis development and that the miRNA profile of adult testis with CIS cells
      shares characteristic similarities with the expression in foetal gonocytes.

PMID- 22420007
TI  - The role of mTOR inhibitors in the inhibition of growth and cortisol secretion in
      human adrenocortical carcinoma cells.
AB  - Patients with adrenocortical carcinoma (ACC) need new treatment options. The aim
      of this study was to evaluate the effects of the mTOR inhibitors sirolimus and
      temsirolimus on human ACC cell growth and cortisol production. In H295, HAC15,
      and SW13 cells, we have evaluated mTOR, IGF2, and IGF1 receptor expressions; the
      effects of sirolimus and temsirolimus on cell growth; and the effects of
      sirolimus on apoptosis, cell cycle, and cortisol production. Moreover, the
      effects of sirolimus on basal and IGF2-stimulated H295 cell colony growth and on
      basal and IGF1-stimulated phospho-AKT, phospho-S6K1, and phospho-ERK in H295 and
      SW13 were studied. Finally, we have evaluated the effects of combination
      treatment of sirolimus with an IGF2-neutralizing antibody. We have found that
      H295 and HAC15 expressed IGF2 at a >1800-fold higher level than SW13. mTOR
      inhibitors suppressed cell growth in a dose-/time-dependent manner in all cell
      lines. SW13 were the most sensitive to these effects. Sirolimus inhibited H295
      colony surviving fraction and size. These effects were not antagonized by IGF2,
      suggesting the involvement of other autocrine regulators of mTOR pathways. In
      H295, sirolimus activated escape pathways. The blocking of endogenously produced
      IGF2 increased the antiproliferative effects of sirolimus on H295. Cortisol
      production by H295 and HAC15 was inhibited by sirolimus. The current study
      demonstrates that mTOR inhibitors inhibit the proliferation and cortisol
      production in ACC cells. Different ACC cells have different sensitivity to the
      mTOR inhibitors. mTOR could be a target for the treatment of human ACCs, but
      variable responses might be expected. In selected cases of ACC, the combined
      targeting of mTOR and IGF2 could have greater effects than mTOR inhibitors alone.

PMID- 22420016
TI  - 238Pu: accumulation, tissue distribution, and excretion in Mayak workers after
      exposure to plutonium aerosols.
AB  - The alpha spectrometry measurements of specific activity of 238Pu and 239Pu in
      urine from bioassay examinations of 1,013 workers employed at the radiochemical
      and plutonium production facilities of the Mayak Production Association and in
      autopsy specimens of lung, liver, and skeleton from 85 former nuclear workers who
      died between 1974-2009, are summarized.The accumulation fraction of 238Pu in the
      body and excreta has not changed with time in workers involved in production of
      weapons-grade plutonium production (e.g., the plutonium production facility and
      the former radiochemical facility). The accumulation fraction of 238Pu in
      individuals exposed to plutonium isotopes at the newer Spent Nuclear Fuel
      Reprocessing Plant ranged from 0.13% up to 27.5% based on the autopsy data. No
      statistically significant differences between 238Pu and 239Pu in distribution by
      the main organs of plutonium deposition were found in the Mayak workers. Based on
      the bioassay data,the fraction of 238Pu activity in urine is on average 38-69% of
      the total activity of 238Pu and 239Pu, which correlates with the isotopic
      composition in workplace air sampled at the Spent Nuclear Fuel Reprocessing
      Plant. In view of the higher specific activity of 238Pu, the contribution of
      238Pu to the total internal dose, particularly in the skeleton and liver, might
      be expected to continue to increase, and continued surveillance is recommended.

PMID- 22420017
TI  - 238Pu: a review of the biokinetics, dosimetry, and implications for human
      exposures.
AB  - Plutonium-238 (238Pu) has a half-life of about 87.7 y and thus a higher specific
      activity than 239Pu. It is used in radioisotope thermoelectric generators and is
      a substantial source of plutonium alpha-radiation in spent nuclear fuels. Early
      animal studies demonstrated differences in the biokinetics of inhaled oxides of
      238Pu and 239Pu with 238Pu having a substantially more rapid translocation from
      the lungs to the systemic organs, particularly the skeleton. This resulted in the
      predominant occurrence of skeletal cancers in animals exposed to 238Pu oxides but
      lung cancers in those with exposures to 239Pu oxides. The anatomical distribution
      of osteogenic sarcomas seen in animal studies was similar to that observed with
      239Pu and also in plutonium workers but differed from naturally occurring tumors.
      The in vivo "solubility" of 238Pu has been associated with the relative amounts
      of 238Pu/239Pu in the particles and calcination temperatures during the
      preparation of the dioxides. There is experimental evidence of in vivo 238Pu
      particle fragmentation attributed to nuclear recoil during radioactive decay. The
      resulting conversion of microparticles to nanoparticles may alter their
      interactions with macrophages and transport across epithelial barriers. There are
      few documented cases of human exposures, but the biokinetics appeared to depend
      on the chemical and physical nature of the aerosols. Robust human biokinetic and
      dosimetric models have not been developed, due in part to the lack of data. With
      the acceleration of nuclear technologies and the greater demand for reprocessing
      and/or disposal of spent nuclear fuels, the potential for human exposure to 238Pu
      will likely increase in the future.

PMID- 22420018
TI  - Exposure of the Swiss population by medical x-rays: 2008 review.
AB  - Nationwide surveys on radiation dose to the population from medical radiology are
      recommended in order to follow the trends in population exposure and ensure
      radiation protection.The last survey in Switzerland was conducted in 1998,and the
      annual effective dose from medical radiology was estimated to be 1 mSv y j(-1)
      per capita. The purpose of this work was to follow the trends in diagnostic
      radiology between 1998 and 2008 in Switzerland and determine the contribution of
      different modalities and types of examinations to the collective effective dose
      from medical x-rays. For this reason, an online database(www.raddose.ch) was
      developed. All healthcare providers who hold a license to run an x-ray unit in
      the country were invited to participate in the survey. More than 225
      examinations, covering eight radiological modalities, were included in the
      survey. The average effective dose for each examination was reassessed. Data from
      about 3,500 users were collected (42% response rate). The survey showed that the
      annual effective dose was 1.2 mSv/capita in 2008. The most frequent examinations
      are conventional and dental radiographies (88%). The contribution of computed
      tomography was only 6% in terms of examination frequency but 68% in terms of
      effective dose. The comparison with other countries showed that the effective
      dose per capita in Switzerland was in the same range as in other countries with
      similar healthcare systems, although the annual number of examinations performed
      in Switzerland was higher.

PMID- 22420019
TI  - Exposure rate constants and lead shielding values for over 1,100 radionuclides.
AB  - The authors have assembled a compilation of exposure rate constants, f-factors,
      and lead shielding thicknesses for more than 1,100 radionuclides described in
      ICRP Publication 107. Physical data were taken from well established reference
      sources for mass-energy absorption coefficients in air, attenuation coefficients,
      and buildup factors in lead and other variables.The data agreed favorably for the
      most part with those of other investigators; thus this compilation provides an up
      to-date and sizeable database of these data, which are of interest to many for
      routine calculations. Emissions were also segregated by emitting nuclide, and
      decay product emissions were emitted from the calculated coefficients, thus for
      the first time providing for the calculation of exposure rates from arbitrary
      mixtures of nuclides in arbitrary equilibrium states.

PMID- 22420020
TI  - Guidance on the use of handheld survey meters for radiological triage: time
      dependent detector count rates corresponding to 50, 250, and 500 mSV effective
      dose for adult males and adult females.
AB  - In June 2006, the Radiation Studies Branch of the Centers for Disease Control and
      Prevention held a workshop to explore rapid methods of facilitating radiological
      triage of large numbers of potentially contaminated individuals following
      detonation of a radiological dispersal device. Two options were discussed. The
      first was the use of traditional gamma cameras in nuclear medicine departments
      operated as makeshift wholebody counters. Guidance on this approach is currently
      available from the CDC. This approach would be feasible if a manageable number of
      individuals were involved, transportation to the relevant hospitals was quickly
      provided, and the medical staff at each facility had been previously trained in
      this non-traditional use of their radiopharmaceutical imaging devices. If,
      however,substantially larger numbers of individuals (100's to 1,000's) needed
      radiological screening, other options must be given to first responders, first
      receivers, and health physicists providing medical management. In this study, the
      second option of the workshop was investigated--the use of commercially available
      portable survey meters (either NaI or GM based) for assessing potential ranges of
      effective dose (< 50, 50-250, 250-500,and >500 mSv). Two hybrid computational
      phantoms were used to model an adult male and an adult female subject internally
      contaminated with 241Am, 60Cs, 137Cs, 131I, or 192Ir following an acute
      inhalation or ingestion intake. As a function of time following the exposure, the
      net count rates corresponding to committed effective doses of 50, 250, and 500
      mSv were estimated via Monte Carlo radiation transport simulation for each of
      four different detector types, positions, and screening distances.Measured net
      count rates can be compared to these values, and an assignment of one of four
      possible effective dose ranges could be made. The method implicitly assumes that
      all external contamination has been removed prior to screening and that the
      measurements be conducted in a low background, and possibly mobile, facility
      positioned at the triage location. Net count rate data are provided in both
      tabular and graphical format within a series of eight handbooks available at the
      CDC website (http://www.bt.cdc.gov/radiation/clinicians/evaluation).

PMID- 22420021
TI  - Estimated lag time in global carbon emissions and CO2 concentrations produced by
      commercial nuclear power through 2009 with projections through 2030.
AB  - This study examines the past and future impact of nuclear reactors on
      anthropogenic carbon emissions to the atmosphere. If nuclear power had never been
      commercially developed, what additional global carbon emissions would have
      occurred? More than 44 y of global nuclear power have caused a lag time of at
      least 1.2 y in carbon emissions and CO2 concentrations through the end of 2009.
      This lag time incorporates the contribution of life cycle carbon emissions due to
      the construction and operation of nuclear plants. Cumulative global carbon
      emissions would have been about 13 Gt greater through 2009, and the mean annual
      CO2 concentration at Mauna Loa would have been ~2.7 ppm greater than without
      nuclear power. This study finds that an additional 14-17 Gt of atmospheric carbon
      emissions could be averted by the global use of nuclear power through 2030, for a
      cumulative total of 27-30 Gt averted during the period 1965-2030. This result is
      based on International Atomic Energy Agency projections of future growth in
      nuclear power from 2009-2030, modified by the recent loss or permanent shutdown
      of 14 reactors in Japan and Germany

PMID- 22420022
TI  - Annual committed effective dose from olive oil (due to 238U, 232Th, and 222Rn)
      estimated for members of the Moroccan public from ingestion and skin application.
AB  - Olive oil is traditionally refined and widely consumed by Moroccan rural
      populations. Uranium (238U), thorium (232Th), radon (222Rn), and thoron (220Rn)
      contents were measured in various locally produced olive oil samples collected in
      rural areas of Morocco. These radionuclides were also measured inside various
      bottled virgin olive oils consumed by the Moroccan populations. CR-39 and LR-115
      type II solid state nuclear track detectors (SSNTDs) were used. Annual committed
      effective doses due to 238U, 232Th, and 222Rn from the ingestion of olive oil by
      the members of the general public were determined. The maximum total committed
      effective dose due to 238U, 232Th, and 222Rn from the ingestion of olive oil by
      adult members of Moroccan rural populations was found equal to 5.9 uSv y-1. The
      influence of pollution due to building material dusts and phosphates on the
      radiation dose to workers from the ingestion of olive oil was investigated, and
      it was found that the maximum total committed effective dose due to 238U, 232Th,
      and 222Rn was on the order of 0.22 mSy y-1. Committed effective doses to skin due
      to 238U, 232Th, and 222Rn from the application of olive oil masks by rural women
      were evaluated. The maximum total committed effective dose to skin due to 238U,
      232Th, and 222Rn was found equal to 0.07 mSy y-1 cm-2.

PMID- 22420023
TI  - Further comments on the induction of lung tumors by plutonium dioxide in beagles.
AB  - A series of recent papers describes the final results obtained from studies of
      the effects of inhaled plutonium dioxide on beagle dogs. This note considers the
      value of a microdosimetric assessment of these data. In particular, it offers
      support for the existence of a threshold for the induction of lung tumors.

PMID- 22420024
TI  - Riboflavin-UVA-induced corneal collagen cross-linking in pediatric patients.
AB  - PURPOSE: Evaluation of stability and functional response after riboflavin-UVA
      induced cross-linking in a population of patients younger than 18 years with
      progressive keratoconus after 36 months of follow-up. METHODS: Prospective
      nonrandomized phase II open trial conducted at the Department of Ophthalmology,
      Siena University, Italy. The "Siena CXL Pediatrics" trial involved 152 patients
      aged 18 years or younger (10-18 years) with clinical and instrumental evidence of
      keratoconus progression. The population was divided into 2 groups according to
      corneal thickness (>450 and <450 MUm) at the time of enrollment. The riboflavin
      UVA-induced corneal cross-linking was performed in all patients according to the
      standard epi-off protocol. Parameters recorded preoperatively and postoperatively
      were as follows: uncorrected visual acuity, best spectacle-corrected visual
      acuity, corneal topography and surface aberrometry (CSO Eye Top topographer;
      Florence, Italy), optical pachometry (Visante OCT; Zeiss Meditec, Jena, Germany),
      and HRT II confocal microscopy (Rostock Cornea Module, Heidelberg, Germany).
      RESULTS: Functional data at 36 months showed an increase of +0.18 and +0.16
      Snellen lines for uncorrected visual acuity and best spectacle-corrected visual
      acuity, respectively, in the thicker group (corneal thickness >450 MUm) and +0.14
      and +0.15 Snellen lines, respectively, in the thinner group (corneal thickness
      <450 MUm). Patients in the latter group already showed a better and faster
      functional recovery than the thicker group at 3-month follow-up. Topographic
      results showed statistically significant improvement in K readings and asymmetry
      index values. Coma reduction was also statistically significant. CONCLUSIONS: The
      study demonstrated significant and rapid functional improvement in pediatric
      patients younger than 18 years with progressive keratoconus, undergoing
      riboflavin-UVA-induced cross-linking. In pediatric age, a good functional
      response and keratoconus stability was obtained after corneal cross-linking in a
      36-month follow-up.

PMID- 22420025
TI  - Pinguecula and diabetes mellitus.
AB  - PURPOSE: To assess the relationship between age and the incidence and severity of
      pinguecula in patients with diabetes mellitus, and to compare the grade of
      pinguecula between control subjects and patients with diabetes. METHODS: A total
      of 160 patients with type 2 diabetes aged 31 to 70 years (DM group) and 160
      control subjects aged 31 to 70 years (control group) were enrolled. The grade of
      pinguecula at 2 locations (nasal and temporal) was assessed in all subjects by a
      grading system. RESULTS: There was an age-related increase in the grade of
      pinguecula in both the DMgroup (r = 0.52; P < 0.0001) and the control group (r =
      0.51; P < 0.0001). The grade and prevalence of pinguecula were higher in the DM
      group than in the control group for pinguecula of the nasal conjunctiva (grade: P
      < 0.0001; and prevalence: 55.0% vs. 40.0%, P = 0.0072) and the temporal
      conjunctiva (grade: P < 0.0001; and prevalence: 54.4% vs. 40.0%, P = 0.0100).
      Multivariate logistic regression analysis revealed that age and diabetes were
      associated with an increased prevalence of nasal or temporal pinguecula (all P <
      0.05). Diabetes mellitus was independently associated with the severity of
      pinguecula (nasal: odds ratio = 1.19; temporal: odds ratio = 1.22) after
      adjustment for age. CONCLUSIONS: This is the first assessment of the relationship
      between pinguecula and diabetes mellitus. Our results suggest that diabetes
      mellitus may be a factor associated with the development of pinguecula.

PMID- 22420026
TI  - Performance of automated and manual coding systems for occupational data: a case
      study of historical records.
AB  - BACKGROUND: Occupational data are a common source of workplace exposure and
      socioeconomic information in epidemiologic research. We compared the performance
      of two occupation coding methods, an automated software and a manual coder, using
      occupation and industry titles from U.S. historical records. METHODS: We
      collected parental occupational data from 1920-40s birth certificates, Census
      records, and city directories on 3,135 deceased individuals in the
      Atherosclerosis Risk in Communities (ARIC) study. Unique occupation-industry
      narratives were assigned codes by a manual coder and the Standardized Occupation
      and Industry Coding software program. We calculated agreement between coding
      methods of classification into major Census occupational groups. RESULTS:
      Automated coding software assigned codes to 71% of occupations and 76% of
      industries. Of this subset coded by software, 73% of occupation codes and 69% of
      industry codes matched between automated and manual coding. For major
      occupational groups, agreement improved to 89% (kappa = 0.86). CONCLUSIONS:
      Automated occupational coding is a cost-efficient alternative to manual coding.
      However, some manual coding is required to code incomplete information. We found
      substantial variability between coders in the assignment of occupations although
      not as large for major groups.

PMID- 22420027
TI  - Theoretical study and rate constants calculation for the reactions X + CF3CH2OCF3
      (X = F, Cl, Br).
AB  - The multiple-channel reactions X + CF3CH2OCF3 (X = F, Cl, Br) are theoretically
      investigated. The minimum energy paths (MEP) are calculated at the MP2/6-31 +
      G(d,p) level, and energetic information is further refined by the MC-QCISD
      (single-point) method. The rate constants for major reaction channels are
      calculated by canonical variational transition state theory (CVT) with small
      curvature tunneling (SCT) correction over the temperature range 200-2000 K. The
      theoretical three-parameter expressions for the three channels k1a(T) = 1.24 x
      10(-15T1.24)exp(-304.81/T), k2a(T) = 7.27 x 10(-15T0.37)exp(-630.69/T), and
      k3a(T) = 2.84 x 10(-19T2.51)exp(-2725.17/T) cm3 molecule(-1) s(-1) are given. Our
      calculations indicate that hydrogen abstraction channel is only feasible channel
      due to the smaller barrier height among five channels considered.

PMID- 22420028
TI  - The CBFA2T3/ACSF3 locus is recurrently involved in IGH chromosomal  translocation
      t(14;16)(q32;q24) in pediatric B-cell lymphoma with germinal center phenotype.
AB  - Translocations involving immunoglobulin (IG) loci are the hallmarks of several
      subtypes of B-cell lymphoma. Common to these translocations is that cellular
      proto-oncogenes come under the influence of IG regulatory elements leading to
      deregulated expression. In case of a breakpoint in the IGH switch region,
      oncogene activation can take place on both derivative chromosomes, which means
      that in principle one translocation can result in concurrent activation of two
      genes. By fluorescence in situ hybridization (FISH), we identified a case of
      leukemic B-cell lymphoma in a child with an IGH break and unknown partner.
      Subsequent long-distance inverse PCR revealed fusion of IGH Sl in 14q32 and the
      50 region of CBFA2T3 in 16q24.3, suggesting presence of the t(14;16)(q32;q24.3).
      Candidate oncogenes targeted through this translocation are CBFA2T3 and ACSF3,
      which could be activated on der(16) and der(14), respectively. FISH screening of
      a population-based cohort of B-cell lymphomas from a prospective trial for the
      treatment of lymphoma in childhood (BFM-NHL) identified additionally a follicular
      lymphoma Grade 3/diffuse large B-cell lymphoma with IGH-CBFA2T3/ACSF3
      juxtaposition. Both lymphomas shared expression of CD10 and CD20 in the absence
      of TdT, suggesting a germinal center (GC) B-cell origin. Our data indicate that
      the CBFA2T3/ACSF3 locus is a novel recurrent oncogenic target of IGH
      translocations, which might contribute to the pathogenesis of pediatric GC
      derived B-cell lymphoma.

PMID- 22420029
TI  - Aberrant expression of miR-196a in gastric cancers and correlation  with
      recurrence.
AB  - MicroRNAs (miRNAs) are short noncoding RNAs (~22 nt) that play important roles in
      the pathogenesis of human diseases by negatively regulating gene expression.
      Here, we examined the relationship between miR-196a and gastric cancer.By the
      analysis of 72 gastric cancer samples, we found that the expression level of miR
      196a microRNA significantly increased in primary gastric cancer tissues versus
      adjacent normal tissues. In addition, extracellular miR-196a detected in
      conditioned medium was strongly correlated with its cellular expression status
      and increased circulating miR-196a in patient serum was associated with gastric
      cancer disease status and relapse. Furthermore, ectopic expression of miR-196a
      microRNA promoted the epithelial-mesenchymal transition and migration/invasion
      capabilities of transfected cells, suggesting its oncogenic potential in gastric
      cancer progression. Altogether, our data demonstrate that miR-196a exerts an
      oncogenic role in gastric cancer and miR-196a may be a novel biomarker for
      detecting gastric cancer and for monitoring disease recurrence.

PMID- 22420030
TI  - Osteopontin is an alpha motor neuron marker in the mouse spinal cord.
AB  - Motor neurons (MNs) are designated as alpha/gamma and fast/slow based on their
      target sites and the types of muscle fibers innervated; however, few molecular
      markers that distinguish between these subtypes are available. Here we report
      that osteopontin (OPN) is a selective marker of alpha MNs in the mouse spinal
      cord. OPN was detected in approximately 70% of postnatal choline
      acetyltransferase (ChAT)-positive MNs with relatively large somas, but not in
      those with smaller somas. OPN+/ChAT+ MNs were also positive for NeuN, an alpha MN
      marker, but were negative for Err3, a gamma MN marker. The size distribution of
      OPN+/ChAT+ cells was nearly identical to that of NeuN+/ChAT+ alpha MNs. Group Ia
      proprioceptive terminals immunoreactive for vesicular glutamate transporter-1
      were selectively detected on the OPN+/ChAT+ cells. OPN staining was also detected
      at motor axon terminals at neuromuscular junctions, where the OPN+ terminals were
      positive or negative for SV2A, a marker distinguishing fast/slow motor endplates.
      Finally, retrograde labeling following intramuscular injection of fast blue
      indicated that OPN is expressed in both fast and slow MNs. Collectively, our
      findings show that OPN is an alpha MN marker present in both the soma and the
      endplates of alpha MNs in the postnatal mouse spinal cord.

PMID- 22420031
TI  - N-acetyl cysteine treatment reduces mercury-induced neurotoxicity in the
      developing rat hippocampus.
AB  - Mercury is an environmental toxicant that can disrupt brain development. However,
      although progress has been made in defining its neurotoxic effects, we know far
      less about available therapies that can effectively protect the brain in exposed
      individuals. We previously developed an animal model in which we defined the
      sequence of events underlying neurotoxicity: Methylmercury (MeHg) injection in
      postnatal rat acutely induced inhibition of mitosis and stimulated apoptosis in
      the hippocampus, which later resulted in intermediate-term deficits in structure
      size and cell number. N-acetyl cysteine (NAC) is the N-acetyl derivative of L
      cysteine used clinically for treatment of drug intoxication. Here, based on its
      known efficacy in promoting MeHg urinary excretion, we evaluated NAC for
      protective effects in the developing brain. In immature neurons and precursors,
      MeHg (3 MUM) induced a >50% decrease in DNA synthesis at 24 hr, an effect that
      was completely blocked by NAC coincubation. In vivo, injection of MeHg (5 MUg/g
      bw) into 7-day-old rats induced a 22% decrease in DNA synthesis in whole
      hippocampus and a fourfold increase in activated caspase-3-immunoreactive cells
      at 24 hr and reduced total cell numbers by 13% at 3 weeks. Treatment of MeHg
      exposed rats with repeated injections of NAC abolished MeHg toxicity. NAC
      prevented the reduction in DNA synthesis and the marked increase in caspase-3
      immunoreactivity. Moreover, the intermediate-term decrease in hippocampal cell
      number provoked by MeHg was fully blocked by NAC. Altogether these results
      suggest that MeHg toxicity in the perinatal brain can be ameliorated by using
      NAC, opening potential avenues for therapeutic intervention.

PMID- 22420032
TI  - Analysis of exosome release and its prognostic value in human colorectal cancer.
AB  - A significant proportion of extracellular nucleic acids in plasma circulate
      highly protected in tumor-specific exosomes, but it is unclear how the release of
      exosomes is modulated in carcinogenesis. We quantified by cytometry exosomes in
      plasma of 91 colorectal cancer patients to evaluate their potential as a tumor
      indicator and their repercussions on diagnosis and prognosis. We examined the
      involvement of TSAP6, a TP53-regulated gene involved in the regulation of
      vesicular secretion, in levels of circulating exosomes in plasma of colorectal
      patients and in HCT116 TP53-(wild-type and null) human colorectal cancer cell
      lines. The fraction of exosomes in cancer patients was statistically higher than
      in healthy controls (mean rank 1/4 53.93 vs. 24.35). High levels of exosomes in
      plasma of patients correlated with high levels of carcino-embryonic antigen (P
      1/4 0.029) and with poorly differentiated tumors (P 1/4 0.039) and tended to have
      shorter overall survival than patients with low levels (P 1/4 0.056). Release of
      exosomes did not correlate with TSAP6 expression; and regulation of TSAP6 by TP53
      was not shown either in tumor samples or in HCT116 cell lines. Although it was
      not suggested that the TP53/TSAP6 pathway regulates the release of exosomes into
      the plasma of colorectal cancer patients, the level of circulating exosomes may
      be used as a tumor indicator, because it correlates with poor prognosis
      parameters and shorter survival.

PMID- 22420033
TI  - Expression of inflammatory cytokines following acute spinal cord injury in a
      rodent model.
AB  - Many therapies that have been developed for acute spinal cord injury (SCI) either
      influence or are influenced by posttraumatic inflammation. Many such therapies
      have reportedly produced promising neurologic benefits in animal models of SCI,
      but demonstrating convincing efficacy in human clinical trials has remained
      elusive. This discrepancy may be related in part to differences in the
      inflammatory response to SCI between human patients and the widely studied rodent
      models. Our objectives were, therefore, to establish the time course of
      inflammatory cytokine release in the spinal cord of rats after a thoracic
      contusion, to determine whether the cytokine release was injury dependent, and to
      correlate these findings with those that we have recently reported for the
      cerebrospinal fluid (CSF) of human SCI patients. After rodent SCI, GRO (the rat
      equivalent of IL-8), IL-6, IL-1alpha, IL-1beta, IL-13, MCP-1, MIP1alpha, RANTES,
      and TNFalpha were elevated within the spinal cord, whereas IL-12p70 was
      decreased. In human SCI, IL-6, IL-8, and MCP-1 were also elevated within the
      cerebrospinal fluid but at later times than those observed in the rodent spinal
      cord. IL-6, IL-8, and MCP-1 were released in an injury-dependent manner in both
      the rodent model of SCI and the human condition. In this regard, similar patterns
      of expression were observed for a number of inflammatory cytokines after SCI in
      rodent spinal cords and in human CSF. Such proteins may therefore have potential
      utility as biomarkers and surrogate outcome measures for evaluating biological
      response to therapeutic interventions.

PMID- 22420034
TI  - Persistent pulmonary hypertension of the newborn and selective serotonin reuptake
      inhibitors: lessons from clinical and translational studies.
AB  - Two recent studies linking in utero exposure to selective serotonin reuptake
      inhibitors (SSRIs) with persistent pulmonary hypertension of the newborn (PPHN),
      a potentially serious but rare respiratory illness, have made clinicians and
      patients more reluctant to use SSRIs during pregnancy. However, additional
      clinical studies have associated maternal depression rather than SSRI exposure as
      a risk factor for PPHN. This review summarizes the current knowledge regarding
      PPHN pathophysiology, including the role of serotonin and genetic risk factors;
      the effects of SSRIs on pulmonary vasculature; the possible link between SSRIs
      and PPHN; and the diagnosis, clinical management, and prognosis of PPHN.

PMID- 22420035
TI  - Identification and functional analysis of novel micro-RNAs in rat dorsal root
      ganglia after sciatic nerve resection.
AB  - Peripheral nerve injures are quite common in clinical practice, and many studies
      have tried to explore the underlying molecular mechanisms. This study focuses on
      the identification and functional analysis of novel miRNAs in rat dorsal root
      ganglia (DRGs) following sciatic nerve resection, which is a classic model for
      studying peripheral nerve injury and regeneration. By using Solexa sequencing,
      computational analysis, Q-PCR verification, and Dicer knockdown assay, 114 novel
      miRNAs in rats were identified, of which 51 novel miRNAs were first reported in
      rat DRGs, and 63 novel miRNAs were produced at days 1, 4, 7, and 14 following
      sciatic nerve resection. We further predicted target genes of these miRNAs and
      analyzed the biological processes in which they were involved. The identified
      biological processes were consistent with the time frame of peripheral nerve
      injury and regeneration, revealing that these miRNAs were genuine miRNAs related
      to nerve regeneration. Our data provide an important resource for the future
      study of function and regulation of these miRNAs and contribute to elucidation of
      tyhe molecular mechanisms responsible for peripheral nerve injury and
      regeneration.

PMID- 22420036
TI  - Childhood maltreatment predicts unfavorable course of illness and treatment
      outcome in depression: a meta-analysis.
AB  - OBJECTIVES: Evidence suggests that childhood maltreatment may negatively affect
      not only the lifetime risk of depression but also clinically relevant measures of
      depression, such as course of illness and treatment outcome. The authors
      conducted the first meta-analysis to examine the relationship between childhood
      maltreatment and these clinically relevant measures of depression. METHOD: The
      authors conducted searches in MEDLINE, PsycINFO, and Embase for articles
      examining the association of childhood maltreatment with course of illness (i.e.,
      recurrence or persistence) and with treatment outcome in depression that appeared
      in the literature before December 31, 2010. Recurrence was defined in terms of
      number of depressive episodes. Persistence was defined in terms of duration of
      current depressive episode. Treatment outcome was defined in terms of either a
      response (a 50% reduction in depression severity rating from baseline) or
      remission (a decrease in depression severity below a predefined clinical
      significance level). RESULTS: A meta-analysis of 16 epidemiological studies
      (23,544 participants) suggested that childhood maltreatment was associated with
      an elevated risk of developing recurrent and persistent depressive episodes (odds
      ratio=2.27, 95% confidence interval [CI]=1.80-2.87). A meta-analysis of 10
      clinical trials (3,098 participants) revealed that childhood maltreatment was
      associated with lack of response or remission during treatment for depression
      (odds ratio=1.43, 95% CI=1.11-1.83). Meta-regression analyses suggested that the
      results were not significantly affected by publication bias, choice of outcome
      measure, inclusion of prevalence or incidence samples, study quality, age of the
      sample, or lifetime prevalence of depression. CONCLUSIONS: Childhood maltreatment
      predicts unfavorable course of illness and treatment outcome in depression.

PMID- 22420037
TI  - Neuroanatomical evidence for a putative autocrine/paracrine signaling system
      involving nicotinic acetylcholine receptors, purinergic receptors, and nitric
      oxide synthase in the airways.
AB  - Nicotine in tobacco smoke is thought to stimulate sensory nerve fibers by
      receptors that are located on airway epithelial cells and on terminal branches of
      C-fiber afferents, but the exact neurochemical substrate that mediates the
      sensory effects of nicotine associated with cigarette smoking is not clear. ATP
      and nitric oxide (NO) have both been implicated in lung responsiveness to
      airborne chemicals such as nicotine. However, the neuroanatomical and functional
      relationships between nicotinic acetylcholine receptors (nAChRs), purinergic
      signaling, and NO are not known, and the main source of NO in the airways is not
      clear. In the present study, we performed RT-PCR to confirm the presence of mRNA
      for all three isoforms of nitric oxide synthase (NOS), neuronal (n-NOS),
      endothelial (e-NOS), and inducible (i-NOS), in the lung. Sequential double
      labeling was performed to assess the site of expression of the different NOS
      isoforms with respect to nAChRs and purinergic receptors (P2X3R) of the
      intrapulmonary airways. RT-PCR confirmed the presence of n-NOS, e-NOS, and i-NOS
      in the lung, and immunohistochemical studies verified their expression by
      epithelial cells at all levels of the intrapulmonary airways, including the
      terminal and respiratory bronchioles. Sequential double labeling demonstrated
      coexpression of n-NOS and/or i-NOS with nAChR- and P2X3R-expressing cells. These
      neuroanatomical findings suggest that bronchial epithelial cells may be a primary
      source of NO in the intrapulmonary airways and that the production and release of
      NO may be regulated by an autocrine/paracrine signaling system involving nAChRs
      and P2X3Rs.

PMID- 22420038
TI  - Ventral striatum response during reward and punishment reversal learning in
      unmedicated major depressive disorder.
AB  - OBJECTIVE: Affective biases may underlie many of the key symptoms of major
      depressive disorder, from anhedonia to altered cognitive performance.
      Understanding the cause of these biases is therefore critical in the quest for
      improved treatments. Depression is associated, for example, with a negative
      affective bias in reversal learning. However, despite the fact that reversal
      learning is associated with striatal response in healthy individuals and
      depressed individuals exhibit attenuated striatal function on multiple tasks,
      studies to date have not demonstrated striatal involvement in the negative bias
      in reversal learning in depression. In this study, the authors sought to
      determine whether this may be because reversal learning tasks conventionally used
      to study behavior examine reversals only on the basis of unexpected punishment
      and therefore do not adequately separate reward- and punishment-based behavior.
      METHOD: The authors used functional MRI to compare the hemodynamic response to a
      reversal learning task with mixed reward- and punishment-based reversal stages
      between individuals with unmedicated major depressive disorder (N=13) and healthy
      comparison subjects (N=14). RESULTS: Impaired reward (but not punishment)
      reversal accuracy was found alongside attenuated anteroventral striatal response
      to unexpected reward in depression. CONCLUSIONS: Attenuated neurophysiological
      response of the anteroventral striatum may reflect dysfunction in circuits
      involving afferent projections from the orbitofrontal, limbic, and/or
      mesostriatal dopaminergic pathways, which conceivably may, together with the
      ventral striatum, underlie anhedonia in depression. Learning to appreciate and
      enjoy positive life experiences is critical for recovery from depression. This
      study pinpoints a neural target for such recovery.

PMID- 22420039
TI  - Stimulant medication use in children: a 12-year perspective.
AB  - OBJECTIVE: The authors examined the utilization of stimulant medications for the
      treatment of ADHD in U.S. children during the period 1996-2008 to determine
      trends by age, sex, race/ethnicity, family income, and geographic region. METHOD:
      The 1996-2008 database of the Medical Expenditure Panel Survey, a nationally
      representative annual survey of U.S. households, was analyzed for therapeutic
      stimulant use in children age 18 and younger. The data for 1987 were also
      recalculated for reference. RESULTS: An estimated 3.5% (95% confidence
      interval=3.0-4.1) of U.S. children received stimulant medication in 2008, up from
      2.4% in 1996. Over the period 1996-2008, stimulant use increased consistently at
      an overall annual growth rate of 3.4%. Use increased in adolescents (annual
      growth, 6.5%), but it did not significantly change in 6- to 12-year-olds, and it
      decreased in preschoolers. Use remained higher in boys than in girls, and it
      remained consistently lower in the West than in other U.S. regions. While
      differences by family income have disappeared over time, use of stimulants in
      ADHD treatment is significantly lower in racial/ethnic minorities. CONCLUSIONS:
      Overall, pediatric stimulant use has been slowly but steadily increasing since
      1996, primarily as a result of greater use in adolescents. Use in preschoolers
      remains low and has declined over time. Important variations related to
      racial/ethnic background and geographic region persist, thus indicating a
      substantial heterogeneity in the approach to the treatment of ADHD in U.S.
      communities.

PMID- 22420040
TI  - Pressure ulcer prevention: how far we've come....still far to go.

PMID- 22420041
TI  - The Na+/H+ exchanger-1 inhibitor cariporide prevents glutamate-induced necrotic
      neuronal death by inhibiting mitochondrial Ca2+ overload.
AB  - In the brain, Na+/H+ exchanger-1 (NHE-1) activation has a significant impact on
      ischemic injury, and, in recent studies, NHE-1 inhibition has been found to
      protect neurons from ischemic injury. This protective effect has been ascribed to
      the prevention of apoptosis, but neuronal cell death following ischemia is a
      consequence of both necrotic and apoptotic cell death. Here, we evaluated the
      ability of the potent NHE-1 inhibitor cariporide to prevent necrotic cell death
      in an in vitro model of excitotoxic neuronal death. Cariporide (100 nM) was found
      to reduce both glutamate-induced necrotic and apoptotic neuronal cell death. Ca2+
      concentrations were observed to peak twice in cytosol and mitochondria in
      cultured neuronal cells after glutamate exposure, and cariporide was found to
      reduce the second Ca2+ concentration increase, but not the first. Furthermore,
      glutamate-mediated mitochondrial death pathways involving loss of mitochondrial
      membrane potential and reactive oxygen species (ROS) accumulation were found to
      be attenuated by cariporide. In addition, cariporide effectively prevented
      necrosis following exposure to glutamate and ameliorated the mitochondrial Ca2+
      and ROS production increases implicated in necrotic cell death. These results
      suggest that NHE-1 participates in the necrotic cell death process and that its
      inhibition offers a means of preventing both necrosis and apoptosis.

PMID- 22420042
TI  - Obstructive defecation syndrome: answers from experts.

PMID- 22420044
TI  - Regarding the "Editor's note".

PMID- 22420043
TI  - Effect of vagus nerve stimulation during transient focal cerebral ischemia on
      chronic outcome in rats.
AB  - The aim of this study was to investigate the effect of vagus nerve stimulation
      (VNS) on infarct volume and neurological recovery up to 3 weeks following
      transient focal cerebral ischemia. Transient ischemia was produced by filament
      occlusion of the proximal middle cerebral artery (MCA) in rats. The right vagus
      nerve was stimulated starting 30 min after MCA occlusion and consisted of 30-sec
      pulse trains (20 Hz) delivered to the animal's right vagus nerve every 5 min for
      a total period of 60 min (n = 10). All the procedures were duplicated, but no
      stimulus was delivered, in a control group (n = 10). Neurological evaluations
      were performed in all animals at 24 hr, 48 hr, 1 week, 2 weeks, and 3 weeks after
      MCA occlusion; animals were euthanized; and neuronal damage was evaluated in
      hematoxylin-eosin-stained sections. The ischemic lesion volume was smaller in the
      VNS-treated animals in comparison with the nonstimulated group (P < 0.02).
      Although the functional score in both treated and untreated groups improved over
      the 3-week observation period (P < 0.001), there was still a statistically
      significant improvement reszulting from VNS treatment compared with control
      animals (P < 0.05). Cerebral blood flow changes in the MCA territory during
      ischemia did not differ between the VNS-treated animals (31.9% +/- 10.4% of
      baseline) and control animals (29.9% +/- 9.1%; P = 0.6). Stimulation of the vagus
      nerve for only a brief period early in ischemia provides neuroprotection in
      transient ischemia, with neuroprotection persisting for at least 3 weeks.

PMID- 22420045
TI  - Distinct roles of dopamine D3 receptors in modulating methamphetamine-induced
      behavioral sensitization and ultrastructural plasticity in the shell of the
      nucleus accumbens.
AB  - Persistent changes in behavior and psychological function that occur as a
      consequence of exposure to drugs of abuse are thought to be mediated by the
      structural plasticity of specific neural circuits such as the brain's dopamine
      (DA) system. Changes in dendritic morphology in the nucleus accumbens (NAc)
      accompany drug-induced enduring behavioral and molecular changes, yet
      ultrastructural changes in synapses following repeated exposure to drugs have not
      been well studied. The current study examines the role of DA D3 receptors in
      modulating locomotor activity induced by both acute and repeated methamphetamine
      (METH) administration and accompanying ultrastructural plasticity in the shell of
      NAc in mice. We found that D3 receptor mutant (D3-/-) mice exhibited attenuated
      acute locomotor responses as well as the development of behavioral sensitization
      to METH compared with wild-type mice. In the absence of obvious neurotoxic
      effects, METH induced similar increases in synaptic density in the shell of NAc
      in both wild-type and D3-/- mice. These results suggest that D3 receptors
      modulate locomotor responses to both acute and repeated METH treatment. In
      contrast, the D3 receptor is not obviously involved in modulating baseline or
      METH-induced ultrastructural changes in the NAc shell.

PMID- 22420046
TI  - Investigating the contribution of common genetic variants to the risk and
      pathogenesis of ADHD.
AB  - OBJECTIVE: A major motivation for seeking disease-associated genetic variation is
      to identify novel risk processes. Although rare copy number variants (CNVs)
      appear to contribute to attention deficit hyperactivity disorder (ADHD), common
      risk variants (single-nucleotide polymorphisms [SNPs]) have not yet been detected
      using genome-wide association studies (GWAS). This raises the concern as to
      whether future larger-scale, adequately powered GWAS will be worthwhile. The
      authors undertook a GWAS of ADHD and examined whether associated SNPs, including
      those below conventional levels of significance, influenced the same biological
      pathways affected by CNVs. METHOD: The authors analyzed genome-wide SNP
      frequencies in 727 children with ADHD and 5,081 comparison subjects. The gene
      sets that were enriched in a pathway analysis of the GWAS data (the top 5% of
      SNPs) were tested for an excess of genes spanned by large, rare CNVs in the
      children with ADHD. RESULTS: No SNP achieved genome-wide significance levels. As
      previously reported in a subsample of the present study, large, rare CNVs were
      significantly more common in case subjects than comparison subjects. Thirteen
      biological pathways enriched for SNP association significantly overlapped with
      those enriched for rare CNVs. These included cholesterol-related and CNS
      development pathways. At the level of individual genes, CHRNA7, which encodes a
      nicotinic receptor subunit previously implicated in neuropsychiatric disorders,
      was affected by six large duplications in case subjects (none in comparison
      subjects), and SNPs in the gene had a gene-wide p value of 0.0002 for association
      in the GWAS. CONCLUSIONS: Both common and rare genetic variants appear to be
      relevant to ADHD and index-shared biological pathways.

PMID- 22420047
TI  - Single-cell analysis. Preface.

PMID- 22420049
TI  - Barcoding biodiversity.
AB  - Analysis of short, species-specific sequences known as DNA barcodes has become a
      widespread practice in biodiversity and ecological research, and also finds
      practical applications from trade control to biomedicine. One of the challenges
      is to ensure that the molecular information is reliably linked to physical
      specimens in collections.

PMID- 22420048
TI  - Genome-wide analysis of copy number variants in attention deficit hyperactivity
      disorder: the role of rare variants and duplications at 15q13.3.
AB  - OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a common, highly
      heritable psychiatric disorder. Because of its multifactorial etiology, however,
      identifying the genes involved has been difficult. The authors followed up on
      recent findings suggesting that rare copy number variants (CNVs) may be important
      for ADHD etiology. METHOD: The authors performed a genome-wide analysis of large,
      rare CNVs (<1% population frequency) in children with ADHD (N=896) and comparison
      subjects (N=2,455) from the IMAGE II Consortium. RESULTS: The authors observed
      1,562 individually rare CNVs >100 kb in size, which segregated into 912
      independent loci. Overall, the rate of rare CNVs >100 kb was 1.15 times higher in
      ADHD case subjects relative to comparison subjects, with duplications spanning
      known genes showing a 1.2-fold enrichment. In accordance with a previous study,
      rare CNVs >500 kb showed the greatest enrichment (1.28-fold). CNVs identified in
      ADHD case subjects were significantly enriched for loci implicated in autism and
      in schizophrenia. Duplications spanning the CHRNA7 gene at chromosome 15q13.3
      were associated with ADHD in single-locus analysis. This finding was consistently
      replicated in an additional 2,242 ADHD case subjects and 8,552 comparison
      subjects from four independent cohorts from the United Kingdom, the United
      States, and Canada. Presence of the duplication at 15q13.3 appeared to be
      associated with comorbid conduct disorder. CONCLUSIONS: These findings support
      the enrichment of large, rare CNVs in ADHD and implicate duplications at 15q13.3
      as a novel risk factor for ADHD. With a frequency of 0.6% in the populations
      investigated and a relatively large effect size (odds ratio=2.22, 95% confidence
      interval=1.5-3.6), this locus could be an important contributor to ADHD etiology.

PMID- 22420050
TI  - Ivan Dikic was trained as a medical doctor at the University of  Zagreb, Croatia.

PMID- 22420051
TI  - Convention (noun): an assembly of persons met for a common purpose.

PMID- 22420053
TI  - Proceedings of the 6th Annual IEEE Conference on Nano/Micro Engineered and
      Molecular Systems (NEMS) 2011, February 20-23, 2011, Kaohsiung, Taiwan.

PMID- 22420052
TI  - Prevalence of otomycosis in Ibadan: a review of laboratory reports.
AB  - Otomycosis has typically been described as fungal infection of the external
      auditory canal with infrequent complications involving the middle ear. Because of
      the dearth of data on the prevalence of Otomycosis in this environment and
      increased rate of immunosuppression, this study was aimed at finding the
      prevalence and fungal etiological agents responsible for this condition.
      Aretrospective review of the laboratory reports of ear swabs of patients that
      presented with signs and symptoms suggestive of fungal infections of the ear like
      otorrhoea, otalgia and aural fullness were done. The diagnosis of otomycosis was
      made on the basis of the recognizable and characteristic appearance of fungal
      hyphae and fruiting bodies under microscopy. The swabs were cultured on the
      Sabouraud Dextrose agar kept at room temperature (27-30 degrees C). Fungi growth
      occurred within 48 hours to 3 weeks. The data collected were analyzed with the
      aid of SPSS version 12.0 computer software. Level of significance was set at
      p<0.05. A total of 53 patients with documented diagnosis of otomycosis were
      included in the analysis and consisted of 31 (58.5%) females and 22 (41.5%)
      males. The ages at diagnosis ranged from 2 to 68 years (Mean: 28.9 yrs; Median:
      30.0 yrs). Otalgia and otorrhoea were the most common symptoms, followed by
      hearing loss and aural fullness. The prevalence of otomycosis among the patients
      in this hospital was 39.6%. Candida albicans was the most common fungal isolate
      in these patients as it occurred in 28.3% (15/53). Other isolates in order of
      frequency were Aspergillus fumigatus (5.7%), A. niger (1.9%), Penicillium spp.
      (1.9%) and Mucor spp.(1.9%). Candida albicans was also the most common fungus
      identified in all age group. There was no statistical significance associated
      between age of presentation and types of fungi isolated (p = 0.054). Even though,
      there was no statistical significance between sex and fungi isolated (p > 0.05),
      it was noted that all the fungi were commonly isolated from female gender
      irrespective of their age. Candida albicans and Aspergillus species were the most
      commonly identified fungal pathogens of otomycosis in U.C. H., Ibadan, Nigeria.
      High index of suspicion should be demonstrated by General practitioners and
      Otorhinolaryngologists. Patients' specimens should be sent to the laboratory as
      early as possible for prompt diagnosis.

PMID- 22420054
TI  - Proceedings of Crossroads of Pathology, November 21-25, 2011, Paris, France.

PMID- 22420055
TI  - Benefits of meeting women's contraceptive needs in Burkina Faso.
AB  - Many women and couples in Burkina Faso do not have the knowledge, means or
      support they need to protect their reproductive health and to have the number of
      children they desire. Consequently, many women have more children than they want
      or can care for. Others turn to induced abortion, which is overwhelmingly
      clandestine and potentially unsafe. By helping women and couples plan their
      families and have healthy babies, good reproductive health care--including
      sufficient access to contraceptive services--contributes directly to attaining
      three Millennium Development Goals (MDGs): reducing child mortality, improving
      maternal health, and combating HIV/AIDS. Improving contraceptive services may
      also make meeting other MDGs--such as achieving universal primary education,
      reducing endemic poverty and promoting women's empowerment and equality--easier
      and more affordable. This In Brief aims to chart a course toward better health
      for Burkinabe women and their families by highlighting the health benefits and
      cost savings that would result from improved contraceptive services. Building on
      prior work and using national data to provide estimates for 2009 (see box), it
      describes current patterns of contraceptive use and two hypothetical scenarios of
      increased use to quantify the net benefits to women and society that would result
      from helping women avoid pregnancies they do not want. We focus on the disability
      and deaths that would be averted and the financial resources that would be saved
      through preventing unintended pregnancy.

PMID- 22420056
TI  - [National Days of Laboratory Medicine in Russia--2011. Scientific and Practical
      Conference "Providing Access to Modern Clinical Laboratory Research--Analytical
      Capabilities, Clinical Needs, and Organizational and Economic Conditions".
      Abstracts. October 4-6, 2011, Moscow].

PMID- 22420057
TI  - Drug and drug-related supply promotion by pharmaceutical company representatives
      at VA facilities. Final rule.
AB  - This final rule amends the Department of Veterans Affairs (VA) regulations
      regarding access to VA facilities by pharmaceutical company representatives. The
      purposes of the rule are to reduce or eliminate any potential for disruption in
      the patient care environment, manage activities and promotions at VA facilities,
      and provide pharmaceutical company representatives with a consistent standard of
      permissible business practice at VA facilities. The amendments will facilitate
      mutually beneficial relationships between VA and pharmaceutical company
      representatives.

PMID- 22420058
TI  - Exempting in-home video telehealth from copayments. Direct final rule.
AB  - The Department of Veterans Affairs (VA) is taking final action to amend its
      regulation that governs VA services that are not subject to copayment
      requirements for inpatient hospital care or outpatient medical care.
      Specifically, the regulation is amended to exempt in-home video telehealth care
      from having any required copayment. This removes a barrier that may have
      previously discouraged veterans from choosing to use in-home video telehealth as
      a viable medical care option. In turn, VA hopes to make the home a preferred
      place of care, whenever medically appropriate and possible.

PMID- 22420060
TI  - Match the drug to its side effects.

PMID- 22420059
TI  - Approval tests and standards for closed-circuit escape respirators. Final rule.
AB  - This final rule announces updated requirements that the National Institute for
      Occupational Safety and Health (NIOSH or Agency), located within the Centers for
      Disease Control and Prevention (CDC) in the Department of Health and Human
      Services (HHS or Department), will employ to test and approve closed-circuit
      respirators used for escaping atmospheres considered to be immediately dangerous
      to life and health, including such respirators required by the Mine Safety and
      Health Administration (MSHA) for use in underground coal mines. NIOSH and MSHA
      jointly review and approve this type of respirator used for mine emergencies
      under regulations concerning approval of respiratory protective devices. NIOSH
      also approves these respirators for use in other work environments where escape
      equipment may be provided to workers, such as on vessels operated by U.S. Navy
      and Coast Guard personnel. The purpose of these updated requirements is to enable
      NIOSH and MSHA to more effectively ensure the performance, reliability, and
      safety of CCERs.

PMID- 22420061
TI  - Don't be starstruck by supplements. Celebrity endorsements: who's selling what.

PMID- 22420062
TI  - Junk health insurance: stingy plans may be worse than none at all.

PMID- 22420063
TI  - Medical devices; immunology and microbiology devices; classification of norovirus
      serological reagents. Final rule.
AB  - The Food and Drug Administration (FDA) is classifying norovirus serological
      reagents into class II (special controls). The special control that will apply to
      these devices is the guidance document entitled ''Class II Special Controls
      Guidance Document: Norovirus Serological Reagents.'' The Agency is classifying
      these devices into class II (special controls) because special controls, in
      addition to general controls, will provide a reasonable assurance of safety and
      effectiveness of these devices and there is sufficient information to establish
      special controls.

PMID- 22420064
TI  - Medicare program; revisions to the durable medical equipment, prosthetics,
      orthotics, and supplies (DMEPOS) supplier safeguards. Final rule.
AB  - This final rule removes the definition of "direct solicitation'' and allows
      DMEPOS suppliers, including DMEPOS competitive bidding program contract
      suppliers, to contract with licensed agents to provide DMEPOS supplies, unless
      prohibited by State law. It also removes the requirement for compliance with
      local zoning laws and modifies certain State licensure requirement exceptions.

PMID- 22420065
TI  - Controlled substances and List I chemical registration and reregistration fees.
      Final rule.
AB  - This rule adjusts the fee schedule for DEA registration and reregistration fees
      necessary to recover the costs of the Diversion Control Program relating to the
      registration and control of the manufacture, distribution, dispensing,
      importation, and exportation of controlled substances and List I chemicals as
      mandated by the Controlled Substances Act.

PMID- 22420066
TI  - Recent proposals to limit Medigap coverage and modify Medicare cost sharing.
AB  - As policymakers look for savings from the Medicare program, some have proposed
      eliminating or discouraging "first-dollar coverage" available through privately
      purchased Medigap policies. Medigap coverage, which beneficiaries obtain to
      protect themselves from Medicare's cost-sharing requirements and its lack of a
      cap on out-of-pocket spending, may discourage the judicious use of medical
      services by reducing or eliminating beneficiary cost sharing. It is estimated
      that eliminating such coverage, which has been shown to be associated with higher
      Medicare spending, and requiring some cost sharing would encourage beneficiaries
      to reduce their service use and thus reduce pro-gram spending. However,
      eliminating first-dollar coverage could cause some beneficiaries to incur higher
      spending or forego necessary services. Some policy proposals to eliminate first
      dollar coverage would also modify Medicare's cost sharing and add an out-of
      pocket spending cap for fee-for-service Medicare. This paper discusses Medicare's
      current cost-sharing requirements, Medigap insurance, and proposals to modify
      Medicare's cost sharing and eliminate first-dollar coverage in Medigap plans. It
      reviews the evidence on the effects of first-dollar coverage on spending, some
      objections to eliminating first-dollar coverage, and results of research that has
      modeled the impact of eliminating first-dollar coverage, modifying Medicare's
      cost-sharing requirements, and adding an out-of-pocket limit on beneficiaries'
      spending.

PMID- 22420067
TI  - [Surprise us!].

PMID- 22420068
TI  - [Prevention of early alcohol drinking, from primary school].

PMID- 22420069
TI  - [Better detection of neonatal cholestasis].

PMID- 22420070
TI  - [Rice milk and risk of malnutrition].

PMID- 22420071
TI  - [Monitoring lead exposure in children].

PMID- 22420072
TI  - [Infantile tuberculosis. A problematic illness].

PMID- 22420073
TI  - [Tuberculosis, a contagious disease].
AB  - Despite the marked fall in the number of cases of tuberculosis in France, the
      disease remains a public health issue due to its contagiousness and the current
      emergence of forms resistant to classic antituberculotics. Prevention and the
      systematic screening of the people close to the patient help to control the
      spread of the disease.

PMID- 22420074
TI  - [Epidemiology of tuberculosis in France].

PMID- 22420075
TI  - [Clinical forms and treatment of tuberculosis in children].
AB  - In France, the incidence of tuberculosis has been in constant decline over recent
      decades which has resulted in the lifting of mandatory vaccination as well as a
      growing lack of awareness of the action to take with a "suspect" child. Treatment
      should be coordinated between doctors from anti-tuberculosis centres and
      specialised hospital departments.

PMID- 22420076
TI  - [History and current situation of BCG vaccinations].
AB  - Vaccination using Bacillus Calmette-Guerin (BCG) discovered at the beginning of
      the 20th century in France, saved many lives in a period where tuberculosis was
      extremely widespread in our country. Mandatory for children since the 1950s, the
      vaccination programme has now been revised and concerns only well-defined
      situations considered to be at risk.

PMID- 22420077
TI  - [The prevention of tuberculosis through screening].
AB  - Tuberculosis is one the world's biggest health problems. The prevention of this
      disease is adapted to the epidemiological situation and the economic constraints
      of each country. The correct treatment of patients as well as the care of people
      having been in contact with them are very effective methods which lead to the
      drop in the incidence and morbidity of tuberculosis.

PMID- 22420078
TI  - [The role of the PMI early childhood worker in the face of tuberculosis].
AB  - Despite the stabilisation of infant tuberculosis, the BCG vaccine remains
      strongly recommended for people at risk and regions with a high prevalence. The
      work of the early childhood worker in maternal and child protection centres (PMI)
      is crucial from the very first meeting, in order to inform and raise the
      awareness of families about the importance of early vaccination.

PMID- 22420079
TI  - [Issues linked to tuberculosis in child day care nurseries].
AB  - Despite a significant fall in the number of cases declared across France,
      instances of tuberculosis still occur.While the BCG vaccination is no longer
      mandatory for accessing child day care facilities, it remains highly recommended
      for children at risk, especially for those living in Ile-de-France.

PMID- 22420080
TI  - [Compliance with antitubercular treatments and prevention].

PMID- 22420081
TI  - [Support and social care of tuberculosis in pediatrics].
AB  - Cases of tuberculosis may have declined but the disease is nevertheless present.A
      social and economic pathology, it affects the most vulnerable and marginalised
      people, who, confronted with numerous obstacles, do not always manage to adhere
      to the treatment and/or its follow-up. Action by social services is essential in
      the treatment and care of people suffering from tuberculosis.

PMID- 22420082
TI  - [Screening and prevention of tuberculosis, an experiment in Marseille].
AB  - In order to apply the recommendations of the French High Council on Public Health
      (CSHPF), the association "Medecins du Monde" and the departmental centre for the
      fight against tuberculosis led; in 2010-2011, two campaigns for on-site
      screening, in Marseille, with Roma families in situations of precariousness.
      These campaigns came up against a number of difficulties which must be addressed
      in order to make them more effective.

PMID- 22420083
TI  - [Bibliography. Infantile tuberculosis].

PMID- 22420084
TI  - [Improving the care of postoperative pain in tonsillectomies].
AB  - The readjustment of professional practices is a quality approach which forms part
      of an interdisciplinary approach. This requires coherence between the actions of
      each player. In this context, a study was carried out at the Liege Christian
      General Hospital (Belgium) to improve pain treatment for children after a
      tonsillectomy.

PMID- 22420085
TI  - [Ethics and dietetics in the hospital].
AB  - The practice of hospital dietetics in children is a response to biological and
      nutritional concerns related to the pathology. It rarely takes into account any
      of the ethical questions, nevertheless essential, which arise in the relationship
      built around food. Through the perspective of nutritionists, researchers and
      philosophers, dietetics in hospital takes an ethical dimension.

PMID- 22420086
TI  - [Hand and wrist injuries].

PMID- 22420087
TI  - Lessons learned in peer workforce development.

PMID- 22420088
TI  - Work in progress: New technology, old questions.

PMID- 22420089
TI  - A fitness movement.

PMID- 22420090
TI  - Accept no substitutes.

PMID- 22420091
TI  - More than 'just a pharmacy'.

PMID- 22420092
TI  - Patient bathrooms can look more 'normal' and still be safe.

PMID- 22420093
TI  - [The "Revue Medicale de Liege", publishing trends in changing society and
      medicine ].

PMID- 22420094
TI  - [Image of the month: pulmonary artery agenesis associated with right lung
      hypoplasia].

PMID- 22420095
TI  - [Lady Windermere syndrome].
AB  - We describe the case of a 68 year old lady with a pectus excavatum, chronic
      cough, dyspnoea, and fever. The CT scan showed fibronodular infiltrates and
      bronchectases. Bacterial culture revealed a Mycobacterium avium-intracellulare
      infection. A tritherapy was initiated and, 10 months later, the patient had
      greatly improved.

PMID- 22420096
TI  - [2011 ESC guidelines for the management of acute coronary syndromes without ST
      segment elevation].
AB  - New European guidelines about the management of non-ST elevated acute coronary
      syndromes emphasize the importance of early risk stratification. This article
      summarizes the modifications in the guidelines about risk stratification and
      invasive management of these syndromes.

PMID- 22420097
TI  - [Post-traumatic stress disorder and psychological debriefing: a controversial
      topic].
AB  - The last decades have demonstrated the value of early interventions after a
      traumatic event. The purpose of these interventions is to prevent the development
      of psychological consequences such as post-traumatic stress disorder.
      Psychological debriefing is clearly the most popular intervention. However, in
      the literature, it is subject to a real controversy. The objective of the present
      paper is to define the interest of psychological debriefing, but also alternative
      therapeutical strategies for people exposed to traumatic events.

PMID- 22420098
TI  - [Obstetrical epidural analgesia and postpartum backache].
AB  - Backache is a common problem in the general population. The prevalence of
      backpain is increased during pregnancy and after delivery. Early studies have
      suggested that labor epidural analgesia might be associated with an increased
      incidence of backache in the postpartum period. However, these initial studies
      were retrospective and their design included several methodological deficiencies.
      All the prospective studies published afterwards (prospective cohort studies and
      3 randomized controlled trials) yield the same result: there is no relationship
      between labor epidural analgesia and long-term postpartum backpain. Pregnant
      women must be aware of this in order to make an informed and appropriate choice
      about labor epidural analgesia, the most effective technique for intrapartum pain
      relief.

PMID- 22420099
TI  - [Bronchial artery ligation for the management of hemoptysis].
AB  - Hemoptysis is defined by the expectoration of blood from infra-glottal airway.
      Massive hemoptysis can be a life-threatening intrathoracic disease that requires
      urgent investigations and management. The chest radiography and the computed
      tomography (CT) are useful to localize the bleeding site and to identify the
      cause of hemoptysis. Bronchial artery embolization is the most effective
      nonsurgical treatment in the management of massive and recurrent hemoptysis. This
      article reviews the role of radiology in the diagnosis and treatment of
      hemoptysis.

PMID- 22420100
TI  - [Delirium, depression, dementia: solving the 3D's].
AB  - As there is no consensus in the specialized literature, it is often difficult to
      recognize the ties existing between dementia, delirium and depression. Depression
      preceding dementia is well-documented. Depressive symptoms during the process of
      dementia are less well-known. So are the close relationships between dementia and
      delirium as well as between delirium and depression. The commonality of symptoms
      between the three often causes diagnostic dilemmas. Unfortunately, elderly
      patients can often present two, or even three, of the "3 D's" simultaneously.
      Untangling the 3 D's has been the subject of several articles. We propose a
      synthesis as well as our thoughts on the subject from a clinical psychogeriatric
      standpoint.

PMID- 22420101
TI  - [A pin-point pattern of rapid occurrence on the skin of adolescents].
AB  - In some instances, a dermatosis exhibits a rapid and focal surge of seemingly
      similar tiny lesions. We report a few typical exemples occurring in adolescents.

PMID- 22420102
TI  - [BNP and NT-proBNP: reference values and cutoff limits].
AB  - Natriuretic peptides, particularly BNP and NT-proBNP, are increasingly used as
      screening test in patients with symptoms suggestive of heart failure (HF). Due to
      their high negative predictive values, natriuretic peptide determinations allow
      to exclude chronic HF with great certainty and to identify patients for whom
      echography is not necessary. These biomarkers are also useful for diagnostic
      purposes, high plasma levels being related to an increased risk of cardiovascular
      hospitalisation and death. Risk stratification in patients with HF symptoms is
      based on "low" and "high" cut-off limits, for which different values have been
      proposed. The aim of this paper is to discuss the delineation of the decision
      limits and the intermediate grey zone in comparison to NT-proBNP reference values
      obtained in a representative group of subjects living in the Liege area
      (Belgium). Data were analysed in relation to age and gender, two of the main
      parameters influencing the natriuretic peptide plasma levels.

PMID- 22420103
TI  - [How I explore ... primary cicatricial alopecias].
AB  - Primary cicatricial alopecias (PCA) result from the inflammatory destruction of
      the hair follicle, followed by its replacement by a fibrotic streamer. The
      involvement of multipotent stem cells of the hair follicle is possible through a
      transdifferentiation pathway. The diagnosis relies on clinico-pathologic
      correlations. PCA are classified as the neutrophilic, lymphocytic and mixed
      types. Each of these groups gather specific disorders including folliculitis
      decalvans, dissecting folliculitis of the scalp, erosive pustulosis of the scalp,
      keloidal acne of the nape, frontal fibrosing alopecia, lichen planopilaris and
      lupus erythematosus.

PMID- 22420104
TI  - [Which blood pressure targets in patients with type 2 diabetes?].
AB  - Arterial hypertension is commonly observed in patients with type 2 diabetes and
      aggravates cardiovascular and renal outcomes. Lowering blood pressure is thus a
      key objective in this population. However, systolic and diastolic blood pressure
      levels to be reached remain controversial and targets should probably be adjusted
      according to patient's individual characteristics ("personalized medicine"). This
      clinical case summarizes the main arguments for selecting blood pressure targets,
      as far as benefits/risks ratio is concerned, in type 2 diabetic patients with a
      metabolic syndrome but without complications, with a nephropathy, or with
      coronary artery disease.

PMID- 22420105
TI  - Relationship between impulsiveness and deviant behavior among adolescents in the
      classroom: age and sex differences.
AB  - To assess the relationship between impulsiveness and deviant behavior among 103
      adolescents, taking into account their sociodemographic characteristics, the
      Barratt Impulsiveness Scale and a self-assessment measure with regard to
      disruptive and deviant behaviors which had occurred in the last 90 days were
      used. The results show that impulsiveness and disruptive behavior in the
      classroom were related to deviant behavior outside of the classroom. Therefore,
      age and sex explained the relationship between impulsiveness and behavior. The
      older adolescents and the girls showed less disruptive behaviors than the younger
      participants and the boys; both variables showed an interactive effect on
      disruptive behavior. The age at which sexual activity commenced and the number of
      sexual partners were also significantly related to impulsiveness and disruptive
      and deviant behavior. Similarly, impulsiveness was shown to have a significant
      relationship with disruptive and deviant behavior, and disruptive behavior was
      shown to have a significant relationship with deviant behavior.

PMID- 22420106
TI  - Effect of respondent code location on survey response rate.
AB  - Survey response rates were examined for differences based on the location of the
      respondent code, a numerical code placed on the survey versus a numerical code
      placed on the return envelope. A four-page survey on criteria and procedures used
      when hiring health education faculty members was mailed to program coordinators
      of university health education programs (N = 223). Half of the coordinators (n =
      112) received coded surveys (surveys that had a written overt three-digit code at
      the top right corner of the first page of the survey). The other half of the
      coordinators (n = 111) received coded return envelopes (return envelopes with a
      six-digit code typed directly under the return mailing address). A total of 132
      coordinators returned completed surveys (62%). Response rate did not differ
      significantly based on placement of respondent code. Survey researchers are thus
      recommended to devote their efforts to other inducement strategies to increase
      response rates.

PMID- 22420107
TI  - Factors affecting the extent of Monday blues: evidence from a meta-analysis.
AB  - A meta-analysis of 34 samples identified a small but reliable "Monday blues"
      effect (-.08 < or = d < or = -.06) in samples reporting current or real-time
      moods for each day of the week. However, the size of the effect in samples
      reporting recalled summaries of moods experienced over the course of a day varied
      depending on whether the sample involved university students or nonstudents.
      University students reporting recalled summaries of daily moods showed a large
      Monday blues effect (d = -.25), whereas married men who were not students
      reported smaller effects with greater variance (-.19 < or = d <or = -.01). The 34
      samples reporting recalled summaries of moods experienced over multiple days
      produced effects ranging from -.25 to -1.28, but the variance among these samples
      was too great to estimate an aggregated statistic.

PMID- 22420108
TI  - Trait valence and the better-than-average effect.
AB  - People tend to regard themselves as having superior personality traits compared
      to their average peer. To test whether this "better-than-average effect" varies
      with trait valence, participants (N = 154 students) rated both themselves and the
      average student on traits constituting either positive or negative poles of five
      trait dimensions. In each case, the better-than-average effect was found, but
      trait valence had no effect. Results were discussed in terms of Kahneman and
      Tversky's prospect theory.

PMID- 22420109
TI  - The effect of social marketing communication on safe driving.
AB  - Processing of cognition, affect, and intention was investigated in viewers of
      advertisements to prevent speeding while driving. Results indicated that
      anchoring-point messages had greater effects on viewers' cognition, attitude, and
      behavioral intention than did messages without anchoring points. Further, the
      changes in message anchoring points altered participants' perceptions of
      acceptable and unacceptable judgments: a higher anchoring point in the form of
      speeding mortality was more persuasive in promoting the idea of reducing driving
      speed. Implications for creation of effective safe driving communications are
      discussed.

PMID- 22420110
TI  - Perceptions of visible piercings: a pilot study.
AB  - 49 undergraduates were shown pictures of a man and a woman with piercings and
      with no piercings. The pierced model was judged to be less attractive and less
      normal than the nonpierced model. The pierced model was perceived as less
      intelligent, caring, generous, honest, and religious but more artistic and
      mysterious.

PMID- 22420111
TI  - The Affect in Play Scale: confirmatory factor analysis in elementary school
      children.
AB  - The aim of this paper was to study the construct validity of the Affect in Play
      Scale, an empirically based measure of pretend play, in a group of 519 Italian
      children ages 6 to 10 years. In confirmatory factor analysis, a correlated two
      factor structure with a cognitive and an affective factor was identified.
      Possible differences in factor scores by sex and age were investigated but no
      significant differences were found.

PMID- 22420112
TI  - The use of feedback in education: a complex instructional strategy.
AB  - The use of feedback to improve students' academic performance involves complex
      instructional strategies. There are a number of instructional problems within
      these strategies that may be overlooked. These include the influence of emotional
      responses, interactions between teacher and student, and levels of cognitive
      processing involved. Feedback should be viewed as an interactive, empirically
      driven, problem-solving process.

PMID- 22420113
TI  - Exploratory factor analysis of the Human Behavior Rating Scale: a rural
      population.
AB  - The construct validity of Eaves' Human Behavior Rating Scale (HBRS) was
      investigated. The HBRS is a scale with 91 Likert-type items designed to measure
      five factors: arousal (persistence and curiosity), affect (externalizing and
      internalizing), and cognition. Forty-four teachers of Grades 6, 7, and 8 from two
      low socioeconomic and rural southern counties completed the HBRS for 320 of their
      students. Three parcels were submitted for analysis for each of the five
      dimensions. A five-factor, then a two-factor, solution were analyzed using
      exploratory factor analysis. A principal-axis factor analysis was employed and an
      oblique promax rotation was applied. The results supported the five-factor
      solution with 90.2% of the total variance accounted for when compared to the two
      factor solution which recovered 73.4% of the total variance. Intercorrelations
      between factors ranged from .15 to .76 for the five-factor solution.

PMID- 22420114
TI  - Psychometric properties of the Padua Inventory in Chinese college samples.
AB  - The aim of the present study was to investigate the psychometric properties of
      the Padua Inventory in Chinese college samples. Three different samples (N1 =
      1,939, N2 = 1,341, and N3 = 298) of Chinese college students were recruited.
      Exploratory factor analyses yielded a four-factor structure which was similar to
      that found in previous studies. Further, present results showed good internal
      consistency as well as convergent and divergent validity with the subscales of
      the Symptom Checklist-90 and the Penn State Worry Questionnaire. Although no sex
      difference was found on total score, women had significantly higher scores on
      Factor 2 (Urges and worries of losing control over motor behaviors) and Factor 4
      (Checking), while men had significantly higher scores on Factor 3
      (Contamination). Implications of ter the results and directions for research are
      discussed.

PMID- 22420115
TI  - Relations among early adolescents' parent-adolescent attachment, perceived social
      competence, and friendship quality.
AB  - To assess whether the relation between attachment and friendship quality may be
      explained by social competence, 113 students in Grades 7 and 8 from the Baltimore
      metropolitan area completed self-report questionnaires on the variables of
      interest. In hierarchical regression analyses, both maternal Affective Quality of
      Attachment and the interaction of School with paternal Affective Quality of
      Attachment predicted social competence. Also, the interaction of School with
      paternal Affective Quality of Attachment predicted negative friendship features,
      whereas social competence predicted positive friendship features. These findings
      provide support for a pathway between adolescents' attachment to both parents and
      adolescents' perceived social competence and, in turn, their friendship quality.

PMID- 22420116
TI  - Acculturation, personality, and psychological adjustment.
AB  - Two studies investigated relationships between traditional indicators of
      acculturation, cultural distance, acculturation strategies, and basic dimensions
      of personality as they pertain to psychological adjustment among Hispanic
      students. Although personality characteristics have been shown to be important
      determinants of psychological well-being, acculturation research has put less
      emphasis on the role of personality in the well-being of immigrants. Hierarchical
      regression analysis showed that basic dimensions of personality such as
      extraversion and neuroticism were strongly related to psychological adjustment.
      Acculturation strategies did not mediate the effect of personality variables, but
      cultural resistance made a small, independent contribution to the explanation of
      some aspects of negative psychological adjustment. The implications of the
      results were discussed.

PMID- 22420117
TI  - Effects of Daylight Saving Time changes on stock market volatility: a reply.
AB  - There is a rich array of evidence that suggests that changes in sleeping patterns
      affect an individual's decision-making processes. A nationwide sleeping-pattern
      change happens twice a year when the Daylight Saving Time (DST) change occurs.
      Kamstra, Kramer, and Levi argued in 2000 that a DST change lowers stock market
      returns. This study presents evidence that DST changes affect the relationship
      between stock market return and volatility. Empirical evidence suggests that the
      positive relationship between return and volatility becomes negative on the
      Mondays following DST changes.

PMID- 22420118
TI  - Child's and parents' catastrophizing about pain is associated with procedural
      fear in children: a study in children with diabetes and their mothers.
AB  - The contribution of the child's and parents' catastrophizing about pain was
      explored in explaining procedural pain and fear in children. Procedural fear and
      pain were investigated in 44 children with Type I diabetes undergoing a finger
      prick. The relationships between parents' catastrophizing and parents' own fear
      and estimates of their child's pain were also investigated. The children and
      their mothers completed questionnaires prior to a routine consultation with the
      diabetes physician. Children completed a situation-specific measure of the Pain
      Catastrophizing Scale for Children (PCS-C) and provided ratings of their
      experienced pain and fear on a 0-10 numerical rating scale (NRS). Parents
      completed a situation-specific measure of the Pain Catastrophizing Scale For
      Parents (PCS-P) d provided estimates of their child's pain and their own
      experienced fear on a 0-10 NRS. Analyses indicated that higher catastrophizing by
      children was associated with more fear and pain during the finger prick. Scores
      for parents' catastrophzing about their children's pain were positively related
      to parents' scores for their own fear, estimates of their children's pain, and
      child-reported fear, but not the amount of pain reported by the child. The
      findings attest to the importance of assessing for and targeting child and
      parents' catastrophizing about pain. Addressing catastrophizing and related fears
      and concerns of both parents and children may be necessary to assure appropriate
      self-management. Further investigation of the mechanisms relating catastrophizing
      to deleterious outcomes is warranted.

PMID- 22420119
TI  - Promoting exercise behavior among Chinese youth with hearing loss: a randomized
      controlled trial based on the transtheoretical model.
AB  - The transtheoretical model proposes that behavior change is experienced as a
      series of stages. Interventions tailored to these stages are most likely to be
      effective in progressing people through the model's hypothesized behavior change
      continuum. In this study, a stage-tailored, 12-week, exercise behavior
      intervention based on the transtheoretical model was conducted among a sample of
      150 Chinese youth with hearing loss. Participants were randomized into an
      intervention or control group with all the core transtheoretical model constructs
      assessed pre- and post-intervention. Participants in the intervention group
      showed greater advances in their stage of exercise behavior change, decisional
      balance, and processes of change use compared to those in the control group. The
      intervention, however, was insufficient for increasing participants' self
      efficacy for exercise behavior. The findings partially support the utility of the
      theory-based intervention for improving the exercise behavior of Chinese youth
      with hearing loss, while simultaneously helping to identify areas in need of
      improvement for future applications.

PMID- 22420120
TI  - Evaluating a brief measure of social self-efficacy among U.S. adolescents.
AB  - Preliminary data were collected to evaluate the performance of a social self
      efficacy measure among 4,061 public high school adolescents. Principal-axis
      factor analysis was followed by a 4-way between-groups analysis of variance
      (ANOVA) to test for differences in the Total score means on selected demographic
      estimates and their interactions. Relations between the Total score and selected
      risk behaviors were examined through a series of one-way ANOVAs and the Tukey HSD
      test. Factor analysis results suggested a one-factor model best explained the
      factor structure of the scale items (factor loading range = .64 - .77, eigenvalue
      = 4.05, h(2) = .51). Females reported a significantly higher mean Total social
      self-efficacy rating than males, while White students reported a significantly
      higher mean Total social self-efficacy rating than Black and Asian students.
      Statistically significant lower mean Total social self-efficacy ratings were also
      noted for those who reported physical fighting, avoiding school, and being
      bullied.

PMID- 22420121
TI  - Training referential communicative skills to individuals with autism spectrum
      disorder: a pilot study.
AB  - The present study reports the effects of referential communication training in
      individuals formally diagnosed with autism spectrum disorder (ASD). Participants
      were 20 children with ASD (M age = 14.3 yr., SD = 4.2; 6 girls, 14 boys) in the
      role of speakers and 20 control children, who acted as listeners. They were all
      enrolled in mainstream compulsory education. Inclusion/exclusion criteria were
      defined according to the clinical diagnosis of ASD, the presence or absence of
      additional or associated disability, previous training in referential
      communication, and any drug treatment. Speakers were randomly assigned to one of
      two groups (trained vs untrained). Linguistic age, cognitive level and autistic
      symptoms were analyzed, respectively, with the Peabody Picture Vocabulary Test
      (PPVT), the Wechsler Intelligence Scale (WISC-R or WAIS-III), and the Autistic
      Behavior Checklist (ABC). Communicative abilities were analyzed through two
      indexes related to message complexity and self-regulation. The trained group was
      trained in referential communication tasks (task analysis, role taking, and task
      evaluation), while the untrained group took part in a communicative game but
      without any specific communicative training. The results showed that the
      complexity of emitted messages had improved statistically significantly in the
      trained group as an effect of training. Ecological referential communication is
      shown to be an appropriate paradigm for studying the communicative process and
      its products and could be used to develop and implement a training program
      focused on those skills in which individuals with ASD are most deficient.

PMID- 22420122
TI  - Perceived parental attachment and achievement motivation.
AB  - A significant amount of research in attachment theory has been devoted to factors
      affecting academic achievement, but less attention has been given to the role of
      attachment in the relation between academic achievement and achievement
      motivation. The current preliminary study examined the role of perceived parental
      attachment in achievement motivation. Self-report data obtained from the Parental
      Attachment Questionnaire, Achievement Goals Questionnaire, and the Performance
      Failure Appraisal Inventory were collected from 50 university students with a
      mean age of 18.8 yr. Correlation and regression analyses indicated that parental
      facilitation of independence correlated significantly and negatively with fear of
      failure. Results yielded partial support for the hypothesis that performance
      oriented goals are related to a fear of failure, whereas mastery-oriented goals
      are not. The results also suggest that high parental attachment in the case of
      high-frequency religious practitioners is related to an increased chance of
      acquiring a more avoidance-oriented achievement motivation.

PMID- 22420123
TI  - The development and validation of the Arabic Scale Of Mental Health (ASMH).
AB  - The objective of this research was to develop and validate the Arabic Scale of
      Mental Health (ASMH) as a generic screening measure and research tool for adults
      and adolescents. Several samples of both sexes were recruited (N = 3,619). Their
      ages ranged between 15 and 71 years. The scale has two equivalent versions:
      Aravic and English. TheASMH comprises 40 brief statements plus 10 filler items.
      Principal components analysis yielded six components labeled: satisfaction, self
      confidence, optimism, enjoyment, meaningful life, and stability. Item-remainder
      correlations ranged between .31 and .79. Reliabilities in these samples indicated
      good internal consistency (alphas= .94 to .96) and temporal stability (7- to 10
      day test-retest r = .84 to .94). The ASMH significantly and positively correlated
      with measures of happiness, satisfaction with life, hope, optimism, love of life,
      and self-actualization, from which one salient component was identified.
      Therefore, initial convergent and factorial validities were adequate. Male
      undergraduates obtained a higher mean score than did both their female
      counterparts and male employed workers, but the effect size was small. It was
      concluded that the ASMH has good psychometric characteristics in its Arabic
      version. The English version merits investigation in a cross-cultural study.

PMID- 22420124
TI  - Accessibility of private and public aspects of traits descriptive of oneself and
      others.
AB  - Previous research has shown that compared to mental representations of others,
      mental representations of ourselves are characterized by relatively greater
      accessibility of private, unobservable content, as opposed to content that is
      public and observable. Are those differences preserved when individuals focus on
      their own public selves and/or on private selves of others? Participants were
      asked to make social judgments involving traits that, in their view, were highly
      descriptive of either public or private selves of themselves, their best friend,
      or an acquaintance. Results demonstrated that highly self-descriptive traits were
      more accessible in social judgments involving individuals' private rather than
      public selves. This was true not only for traits descriptive of one's private
      self but also for traits descriptive of one's public self. Furthermore, other
      descriptive traits, including traits that were highly descriptive of
      representations of private selves of others, were more accessible in social
      judgments involving public rather than private selves.

PMID- 22420125
TI  - Relations of social problem solving with interpersonal competence in Japanese
      students.
AB  - To clarify the relations of the dimensions of social problem solving with those
      of interpersonal competence in a sample of 234 Japanese college students,
      Japanese versions of the Social Problem-solving Inventory-Revised and the Social
      Skill Scale were administered. Pearson correlations between the two sets of
      variables were low, but higher within each set of subscales. Cronbach's alpha was
      low for four subscales assessing interpersonal competence.

PMID- 22420126
TI  - Relative contributions of self-efficacy, self-regulation, and self-handicapping
      in predicting student procrastination.
AB  - The relative contributions of self-efficacy, self-regulation, and self
      handicapping student procrastination were explored. College undergraduate
      participants (N = 138; 40 men, 97 women, one not reporting sex) filled out the
      Procrastination Scale, the Self-Handicapping Scale-Short Form, and the Self
      regulation and Self-handicapping scales of the Motivated Strategies for Learning
      Questionnaire. A hierarchical regression of the above measures indicated that
      self-efficacy, self-regulation, and self-handicapping all predicted scores on the
      Procrastination Scale, but self-regulation fully accounted for the predictive
      power of self-efficacy. The results suggested self-regulation and self
      handicapping predict procrastination independently. These findings are discussed
      in relation to the literature on the concept of "self-efficacy for self
      regulation" and its use in the field of procrastination research.

PMID- 22420127
TI  - Factor structure of the perfectionistic self-presentation scale in Korea.
AB  - This study explored the factor structure of the Korean version of the
      Perfectionistic Self-Presentation Scale, originally developed by Hewitt and
      colleagues in 2003 with three factors (Perfectionistic Self-promotion, Non
      display of Imperfection, and Non-disclosure of Imperfection). In Study 1, a
      confirmatory factor analysis was performed on the Korean version with 27 items
      for 151 Korean college students, but the model fit was poor. Subsequently, an
      exploratory factor analysis was conducted, and the results yielded three factors
      as found in Hewitt, et al., yet with 20 items rather than the original 27 items.
      This new version had good internal consistency (Cronbach's alpha =.88);
      convergent validity estimate was established with a measure of self-presentation
      motivation. In Study 2, to support the structural validity of the Korean version,
      another confirmatory factor analysis was conducted with 203 Korean college
      students. The model fit was good, but a few amendments were made.

PMID- 22420128
TI  - Backward versus forward blocking: evidence for performance-based models of human
      contingency learning.
AB  - Two types of theories are usually invoked to account for cue-interaction effects
      in human-contingency learning, performance-based theories, such as the comparator
      hypothesis and statistical models, and learning-based theories, such as
      associative models. Interestingly, the former models predict two important cue
      interaction effects, forward and backward blocking, should affect responding in a
      similar manner, whereas learning-based models predict the effect of forward
      blocking should be larger than the effect of backward blocking. Previous
      experiments involved important methodological problems, and results have been
      contradictory. The present experiment was designed to explore potential
      asymmetries between forward and backward blocking. Analyses yielded similar
      effect sizes, thereby favoring the explanation by performance-based models.

PMID- 22420129
TI  - Collective self-esteem: role of social context among Asian-American college
      students.
AB  - The present study explored several layers of individual and contextual variables
      as related to collective self-esteem among 304 Asian-American college students.
      The findings suggested that variables, such as immigration generation status and
      cultural identification, were significantly associated with Private collective
      self-esteem (personal evaluation of one's ethnic group), while contextual
      variables, including number of same-ethnicity peers and community ethnic
      composition, were associated with Public collective self-esteem (judgment of how
      other people evaluate one's ethnic group). In addition to these variables, age
      and fluency of heritage language were positively related to Membership esteem
      (how worthy one feels as a member of one's ethnic group). For the Importance of
      identity (the importance of ethnic group membership to one's self-concept),
      cultural identification, number of same-ethnicity peers, and perceived campus
      climate were statistically significant. The implication of the present findings
      for future research is discussed.

PMID- 22420130
TI  - WHO Expert Committee on biological standardization.
AB  - This report presents the recommendations of a WHO Expert Committee commissioned
      to coordinate activities leading to the adoption of international recommendations
      for the production and control of vaccines and other biologicals and the
      establishment of international biological reference materials. The report starts
      with a discussion of general issues brought to the attention of the Committee and
      provides information on the status and development of reference materials for
      various antibodies, antigens, blood products and related substances, cytokines,
      growth factors, and endocrinological substances. The second part of the report,
      of particular relevance to manufacturers and national regulatory authorities,
      contains WHO recommendations and guidelines on Japanese encephalitis vaccine
      (inactivated), human; regulatory preparedness for human pandemic influenza
      vaccines; and clinical evaluation of meningococcal C conjugate vaccines. Also
      included are a list of recommendations, guidelines and other documents for
      biological substances used in medicine, and of international standards and
      reference reagent for biological substances.

PMID- 22420131
TI  - Interview: Helen Darling on reducing healthcare costs.

PMID- 22420132
TI  - Robert Shapiro: a strategy to meet future needs.

PMID- 22420133
TI  - Post-election outlook for providers: a resource-constrained environment.

PMID- 22420134
TI  - 5 ways to provide more connected care.

PMID- 22420135
TI  - Medicare coverage analysis: avoiding compliance pitfalls.
AB  - Healthcare finance leaders should take the following steps to ensure the
      eligibility of a clinical study for Medicare coverage: Centralize the process of
      collecting and archiving all relative components, such as protocol, consent,
      sponsor budgets, and contracts. Establish a standard operating process from the
      time a provider sees a patient to how the service is documented and communicated
      to payers. Provide ongoing education to staff and research personnel to mitigate
      the risk of mistakes.

PMID- 22420136
TI  - Market turbulence creates financing opportunity.
AB  - The flight to high-quality assets resulting from Standard & Poor's downgrade of
      the U.S. government's credit rating has dropped the yield on U.S. Treasury
      securities as investors have sought refuge amid uncertain market conditions.
      Consequently, hospitals can now obtain mortgage insurance from the U.S.
      government to finance expansions and refinance their debt with GNMA securities at
      taxable interest rates that are often more favorable than tax-exempt bond fixed
      rates. Because GNMA certificates can be sold in a forward purchase transaction
      that locks in a fixed interest rate while avoiding payment of interest until
      construction funds are disbursed, they can help avoid the effects of negative
      arbitrage.

PMID- 22420137
TI  - The drive to survive: independent medical practice.
AB  - The "hospital of choice" for independent physicians will have the following
      characteristics: Adequate capital for investment in human resources, technology,
      and facilities. A strong and sustainable market position based on affiliated
      primary care practices. The ability to engage physicians as business partners.
      The availability of performance management information.

PMID- 22420138
TI  - Brent James, MD: using data to transform healthcare delivery. Interview by
      Richard L Clarke.

PMID- 22420139
TI  - Achieving sustainable cost transformation.
AB  - Means for hospitals and health systems to achieve necessary, sustainable cost
      transformation include: Using a structured approach with rigorous analysis.
      Understanding the organization's capital position and quantifing the shortfall.
      Identifing potential savings sources. Using internal and external benchmarks.
      Ensuring integration of cost-reduction targets with organizational plans and
      budget.

PMID- 22420140
TI  - Finding your organization's sweet spots for cost management.
AB  - Healthcare executives from three leading organizations offer these tips for
      driving sustainable improvements in value: Focus on fewer initiatives, execute
      them, make sure that the results are sustainable-then move on. Ensure that both
      clinical and operational experts take part in discussions on ways to improve
      value through care redesign and reengineering of processes throughout the
      organization. Zero in on the elimination of adverse events through evidence-based
      care for quick wins related to quality and cost.

PMID- 22420141
TI  - Cutting costs in your own backyard: opportunities in financial services.
AB  - Hospitals looking to reduce cost and improve performance in financial services
      should focus on these areas: Treasury banking services costs and fees. The
      possibility of a revenue-generating vendor payment solution. The accounts payable
      process.

PMID- 22420142
TI  - Frequent-user patients: reducing costs while making appropriate discharges.
AB  - Homeless patients who lack access to the health resources they need to maintain
      their health on their own pose a challenge for hospitals: Premature discharge of
      such patients can result in their being readmitted to the hospital in a short
      time, leading to higher costs for the hospital. Hospitals can address this
      problem by developing clear, effective homeless discharge policies and by
      developing ongoing relationships with appropriate medical respite care providers.
      A hospital also can benefit from spearheading an initiative to develop a medical
      respite program, enlisting the assistance of other community stakeholders.

PMID- 22420143
TI  - A multidisciplinary approach to denials prevention.
AB  - Children's National Medical Center's approach to preventing denials and managing
      response to audits includes the following: Mapping out problem areas in the
      claims submission process and developing solutions with the help of a
      multidisciplinary team. Using case managers to help prevent denials and assist in
      the appeal of rejected claims. Requesting oral reconsideration of pended claims
      and supporting attending physicians in orally responding to the payer's medical
      team regarding the case.

PMID- 22420145
TI  - Finding a common language for value-based health care.

PMID- 22420144
TI  - Current trends in hospital mergers and acquisitions.
AB  - Healthcare reform will impact hospital consolidation in three key areas: Payment
      rates will decrease, indirectly encouraging consolidation by forcing hospitals to
      find new ways to reduce costs and increase negotiating clout with suppliers and
      payers. The cost of doing business will increase as hospitals spend more on
      compliance, technology, and physician employment. The ACO model will encourage
      hospital network formation by rewarding integrated healthcare systems that can
      reduce costs and improve quality.

PMID- 22420146
TI  - Regional impact of the Medicare value-based purchasing program.

PMID- 22420147
TI  - [An analysis of mental disorders of international students visiting the Mental
      Health Service at Tsukuba University Health Center].
AB  - With the expected increase in the number of international students coming to
      Japan as part of the Ministry of Education, Culture, Sports, Science &
      Technology's "300,000 Foreign Student (Global 30) Plan", the demands on
      university mental health facilities will also increase. However, the rate of
      mental disorders of recent international students has not been fully evaluated.
      As part of an initiative to establish effective treatment measures for the mental
      health of international students, we investigated the present status and recent
      trends of these students who visited the Mental Health Service (MHS) in the
      Tsukuba University Health Center. The demographic characteristics, pathway,
      stress, and diagnosis of international students who visited the MHS from 2005 to
      2010 were investigated retrospectively based on medical records. The subjects
      were 59 international students (15 male, 44 female; mean age: 28.4). The
      consultation rate of international students was significantly lower than that of
      Japanese students each year. Although the rate is almost stable in Japanese
      students (2.1-2.5%), it has increased significantly in international students,
      from 0.5% in 2005 to 1.4% in 2010. A larger percentage of the subjects were from
      Asia (66%), compared to the former Soviet Union (10%) and Europe (7%). A greater
      proportion of the subjects were graduate students (67%). The diagnoses were as
      follows: depression (34%), adjustment disorder (32%), insomnia (15%), and
      schizophrenia (9%). The percentage requiring emergency consultation was 24%,
      including the most severe cases that had to return to their home country. Sixty
      nine percent of the subjects stayed in Japan for more than 1 year. Half of the
      subjects decided to visit the MHS themselves. The results of the present study
      show that the consultation rate of international students was lower than that of
      Japanese students in spite of the "culture shock" experienced by international
      students. This result is in agreement with previous reports. Among international
      students, however, there is a trend indicating an increase of visits to the MHS
      in recent years, approaching the rate for Japanese students. Preparations for
      emergency consultation are still important.

PMID- 22420148
TI  - [What kinds of skills are needed to develop the outreach services in the context
      of community-based mental health?].
AB  - Outreach services in the context of a policy, "from hospital based to community
      based", are intended to know more about community living situation of patients,
      and provide supports so that they can bring their life back as citizens.
      Therefore, these outreach services are completely different from traditional
      monitoring based outreach services. These supports require skills which are
      different from those in psychiatric hospitals. Those differences would be visible
      in terms of skills because staff will be exposed to "life" of patients.
      Furthermore, those differences in skills would come up from necessity of facing
      negative feeling of people who receive outreach services often have toward
      medical care and support. Based on this standpoint, the author proposed tentative
      plan which divided necessary skills for outreach into five phases from the
      viewpoint of the training as follows: Level 1: Shifting perspectives from illness
      management to community living based, Level 2: Knowing their living situations
      and strengths. Building trusting relationship as staying present to the person.
      Level 3: Staying on top of skills in strength model, case management, and
      psychoeducation. Level 4: Being able to work in a team setting smoothly. Level 5:
      Even if the paternalism is necessary in the particular situation, staff needs to
      be able to face that situation without escaping. In addition, the author called
      the attitude of psychiatric facilities toward community psychiatry as
      "regionalization" and divided "regionalization" into six stages while showing
      necessary skills for each stage.

PMID- 22420149
TI  - [How should be a psychiatric hospital to take in and utilize the psycho-social
      approaches in Japan? -- From the view point of psychiatry, medical model, medical
      system and economical management system].
AB  - The author developed argument that a cause of the present condition of our
      country, in which psycho-social approaches have not fully spread though its
      clinical efficacy has been well recognized, is in the medical institution side.
      Because, our psychiatric reforms over 17 years, that reduced the average duration
      of hospitalization from about 2156 days to 61 days, has attained by deployment of
      various psycho-social approaches based on "therapeutic community model" and
      "psychodynamic team treatment". Furthermore, it has done by the affinity,
      continuity and complementarities of "psychodynamic team treatment" and
      psychosocial approaches with following special features. That is, since psycho
      social approaches is 1. techniques to acquire the social life skill and to
      prevent re-hospitalization, 2. the group psychotherapy by facilitating the
      patient's mutual help capability, 3. based on "acceptance of the disease" by
      "noticing the diagnosis". Even if the therapeutic orientation or assumption of
      the psychiatric hospital does not comprehend above all of 1-3, it is important
      whether it is in the same direction or not. In other words, it is the issue of
      the medical-economical-management system, medical model and also the kind of
      psychiatry that is the source of them. Our hospital is for short term
      hospitalization and in focus on the outpatient treatment with "psychodynamic team
      treatment" based on "therapeutic community model". That is why our hospital has a
      potential advantage to take in and utilize the psycho-social approaches. On the
      other hand, there is the same reason why it is difficult for the traditional
      psychiatric hospital for long term hospitalization with higher hierarchical
      "physical medicine model" based on the descriptive psychiatry. The further
      problem is that both psychiatric hospital staff and psycho-social therapists do
      not realize it. The most important issue for us is having the recognition and
      exploring the method not to adapt to a psychiatric hospital but to improve and
      spread psycho-social approaches to psychiatric hospital.

PMID- 22420150
TI  - [The model program of psycho-social treatment and staff training].
AB  - The model program of psycho-social treatment and staff training were reported in
      this issue. The mission of model program is supporting recovery of persons with
      mental illness and their family as well as empowering their hope and sense of
      values. The personal support specialists belonging to multi-disciplinary team
      have responsibility to support life-long process of recovery across
      hospitalization, out-patients clinic, day treatment, and outreach service. The
      shared value of multi-disciplinary team (the community life supporting team) is
      recovery so that the team renders self directive life, various alternatives of
      their lives, and peer group with models of recovery to persons with mental
      illness. There should be several technologies which are used in the team such as
      engagement, psycho-education, cognitive-behavior therapy, care-management,
      cooperating with other resources. The responsibility, assessment and evaluation
      techniques, guarantee of opportunities for training, and auditing system of the
      team and process of treatment are important factors to educate team staff.
      Raising effective multi-disciplinary team requires existence of a mentor or good
      model near the team.

PMID- 22420151
TI  - [Outpatient treatment for patients with eating disorders].
AB  - In the treatment of eating disorders, patients in either the acute or chronic
      stage are generally treated on outpatient basis as much as possible in the living
      condition of daily life. This paper describes the flow of diagnosis and
      treatment, first examination and introduction into treatment, way of parents
      treating their child, parental counseling, criteria for admission (immediate
      hospitalization or not), and outpatient therapy.

PMID- 22420152
TI  - [Morita therapy in a form of outpatient psychotherapy: its theory and technique].
AB  - Beggining in the 1990s, Morita therapy has shifted its principal setting of
      practice to outpatient format to accommodate the changing needs of the era.
      Morita therapy has shifted its "Fumon" (strategic inattention) stance to
      "attending to", and evolved into more dialogue-based psychotherapy. At the same
      time, much attention has been paid to examine its treatment process, therapist
      client relationship, and intervention techniques. The characteristic features of
      the principles of human understanding in Morita therapy reside in its unique
      angle to understand phenomena from relations, conceptualize our experiences from
      dynamism between fear of death and desire for life, and situate Eastern view of
      nature as its foundation. In accordance with the Moritian view of nature, the
      author conceptualizes self as a product of continuous relationship between self
      consciousness, body, and internal nature. The author also conceptualizes a state
      in which we find ourselves in suffering as resulting from inflated self
      consciousness, puniness of body and internal nature, or broken harmony amongst
      them. The fundamental principle of Moritian therapeutic interventions is to
      "trim" such inflated self-consciousness (Should-/Ought-to Thinking), while
      "inflating" body and internal nature (emotion, desire) by facilitating patients'
      behavioral engagement in their day-to-day life world. Concretely speaking, there
      are two intervention methods. One is to intervene by "trimming" to facilitate
      acceptance (and not to make value judgment on self-experience, and to give up
      futile attempt to control affective experience). The other is to intervene by
      "inflating" to facilitate changes in behavior (and to experience day-to-day life
      world directly). Morita therapists intervene by integrative use of these two
      approaches. Treatment process of the outpatient Morita therapy can be divided
      into two stages. The first stage revolves around intervention of symptoms and
      fosters patients to experience the "fluidity" of their symptoms. The next stage
      revolves around self and fosters patients to accept themselves in reality as they
      are and to make the most of him/herself. The goal of Morita therapy is to achieve
      such state of "Arugamama" (being "as-is").

PMID- 22420153
TI  - [Hydrogen sulfide inhibits Ca(2+)-induced mitochondrial permeability transition
      pore opening in adult and old rat heart].
AB  - In experiments in vivo and in vitro on the mitochondria isolated from adult and
      old rat hearts, we studied the effects of a donor of hydrogen sulfide (H2S),
      NaHS, and H2S biosynthesis substrate, L-cysteine, on the sensitivity of the
      mitochondrial permeability transition pore (mPTP) opening to its natural
      inductor, Ca(2+). We found that NaHS (10(-12) to 10(-4) mol/l) influenced
      mitochondrial swelling in a concentration-dependent manner. It was also
      demonstrated that the addition of NaHS (10(-12) to 10(-8) mol/l) to the calcium
      free medium resulted in moderate a swelling of mitochondria from both adult and
      old rat hearts. At 10(-10) mol/l NaHS, the maximal values of the mitochondrial
      swelling observed in both adult and old hearts were 11 and 15 ,%, respectively. A
      specific inhibitor of KATP channels, 5-hydroxydecanoate (5-HD; 10(-4) mol/l)
      decreased the mitochondrial swelling in the presence of NaHS (10)-10) mol/l),
      which can be indicative of the contribution of these channels to the calcium
      independent conductance of the mitochondrial membranes in the rat hearts. The H2S
      donor NaHS used in physiological concentrations (10(-6), 10(-5) and 5 10(-5)
      mol/l) exerted the inhibiting effect on the Ca(2+)-induced mPTP opening in adult
      hearts (corresponding values of such effect were 31, 76, and 77%, respectively),
      while in old hearts the protector effect of NaHS was observed only at its
      concentration of 10(-5) mol/l. Therefore, the donor of H2S used in the tested
      concentrations (10(-12) to 10(-4) mol/l) exerted ambiguous effect on the
      mitochondrial swelling: low concentrations of NaHS (10(-12) to 10(-8) mol/l)
      increased the mitochondrial swelling, while its physiological concentrations (10(
      6) to 5 10(-5) mol/l) exerted the protective effect on Ca(2+)-induced
      mitochondrial swelling in adult and old hearts. Pre-incubation of isolated
      mitochondria with 5-HD (10(-4) mol/l) resulted in a decrease in the protective
      effect evoked by NaHS (10(-5) mol/l) on Ca(2+)-induced mPTP opening, which is
      indicative of the possible involvement of mitochondrial KATP-channels in the H2S
      dependent inhibition of mPTP formation in both adult and old rat hearts. In
      experiments in vivo, single intraperitoneal injections of both NaHS (10(4)
      mol/kg) and L-cysteine ((10(-3) mol/kg) resulted in a decrease in the sensitivity
      of mPTP to its inductor Ca(2+) in adult and old rat hearts. The action of L
      cysteine, as compared with that of NaHS, was more effective in prevention of
      Ca(2+)-induced mitochondrial swelling. We observed a rise in Ca(2+) concentration
      by one order of magnitude, which evoked the mitochondrial swelling in adult and
      old hearts. In experiments in vivo in which we used a specific blocker
      ofcystathionine-g-lyase, propargylglycine (10(-4) mol/kg) that is involved in the
      synthesis of H2S, we observed an increase in the sensitivity of mPTP opening in
      old hearts because of a decrease in the threshold Ca(2+) concentration required
      for mitochondrial swelling by two orders of magnitude. We demonstrate the
      involvement of endogenous H2S in the control of mPTP formation in adult and old
      hearts. Our studies are indicative of the involvement of H2S in modulation of
      changes in the permeability of mitochondrial membranes, which can be an important
      regulatory factor in the development of cardiovascular diseases.

PMID- 22420154
TI  - [Urothelium-dependent modulation of urinary bladder smooth muscle contractions by
      menthol].
AB  - TRPM8 cold receptor/channel is considered amongst the variety of receptors that
      support and modulate sensory function of urothelium, although the information
      regarding this is still quite contradictory. Here we have studied the effects of
      nonspecific TRPM8 activator menthol on the contractions of the smooth muscle
      strips of the rat bladder with intact and removed urothelium, and assessed the
      expression in them of TRPM8 mRNA using semi-quantitative RT-PCR. Menthol (100
      microM) decreased the basal tone and the amplitude of spontaneous contractions
      only in the strips with intact urothelium. Irrespective of the presence of
      urothelium it similarly inhibited (by approximately 45 %) the contractions evoked
      by high-potassium depolarization. Contractions induced by muscarinic agonist
      carbachol (1 microM) were inhibited by menthol much stronger (by approximately
      63%) if the urothelium was present than without it (by approximately 12%).
      Expression of TRPM8 mRNA in urothelium was not detected, whilst in detrusor
      smooth muscle it was found very low. We conclude that modulation of contractile
      responses by menthol is most likely explained by its blocking action on voltage
      gated calcium channels ofdetrusor smooth muscle cells (SMC) and by menthol
      stimulated release from urothelium of some factor(s) with relaxant effects on
      SMCs. Stimulation of the secretion of these factors from urothelial cells most
      likely involves menthol-induced, TRPM8-independent mobilization of calcium.

PMID- 22420155
TI  - [Changes in mRNA and protein expression of antioxidant enzymes in children with
      bronchial asthma after interval hypoxic training].
AB  - The effect of 10 days of interval hypoxic training (IHT) on the mRNA expression
      and protein content of antioxidant enzymes (superoxide dismutase, catalase and
      glutathione-S-transferase) in leukocytes of children with bronchial asthma (BA)
      was investigated. It was shown that after sessions of IHT the mRNA expression of
      superoxide dismutase decreased by 32.5% (P < 0,05), but the level of protein was
      unchanged. The level of catalase gene mRNA and protein content in leukocytes
      after IHT increased by 67% and 13% accordingly. We detected a 90% increase in
      glutathione S-transferase level following IHT.

PMID- 22420156
TI  - [(3-carboxamidino-2-oxo-2H-chromen-7-yl)-4-guanidinobenzoates are novel blockers
      of pH-sensitive ion channels].
AB  - Ischemic stroke is one of the most severe brain pathologies that is extremely
      difficult to treat. Recently it has been found that acidosis accompanying
      cerebral ischemia induces activation of acid-sensing ion channel ASIC1a which
      results in its turn in the neuronal death. Here we present novel derivatives of 3
      carboxamidinocoumarines that effectively inhibit ASIC1a and ASIC3 channels in
      concentration-dependent manner. The most active compound inhibits ASIC1a and
      ASIC3 channels with corresponding IC50 of 7.3 and 13.2 microM. Our data suggest
      that 3-carboxamidinocoumarines can be used as a scaffold for novel type of highly
      efficient anti-ischemic drugs.

PMID- 22420157
TI  - [Genipin--uncoupling protein inhibitor--reduces the protective effect of ischemic
      preconditioning].
AB  - The functional significance of uncoupling proteins UCP2 and UCP3 in the cell and
      the organism remains unknown. There have been reports about their involvement in
      cellular protection mechanisms underlying the phenomenon of ischemic
      preconditioning. The purpose of this study was to elucidate the role of
      uncoupling proteins UCP2 and UCP3 in the formation of cardioprotective effect of
      ischemic preconditioning. In experiments on isolated rat hearts we show here an
      increase in the level of UCP2 and UCP3 gene expression in the heart tissue under
      the influence of ischemic preconditioning with three episodes of 5 min stopping
      the flow perfusion. Similar effects were induced by a prolonged ischemia
      reperfusion of myocardium. The blockade of the UCP2 activity by genipin (Wako
      Inc., USA, 10(-5) mol/L, isolated heart perfusion for 15 minutes) abolished the
      protective effect of adaptation to ischemia. It was concluded that uncoupling
      proteins take part in the cardioprotective effect ofischemic preconditioning.

PMID- 22420158
TI  - [Effect of positive expiratory pressure on pulmonary gas exchange in elderly
      people with accelerated aging].
AB  - The reaction of cerebral blood flow during breathing with positive end expiratory
      pressure in elderly people with physiological (24 pers.) and accelerated (26
      pers.) aging of the respiratory system were studied. It is shown that in people
      with accelerated aging of the respiratory system some resistance to expiration
      improves the efficiency of gas exchange in the lungs. However, breathing with
      considerable resistance to expiration (15 mm water column) in people with
      accelerated aging of the respiratory system, causing depression of gas exchange
      in the lungs. Found that people with accelerated aging of the respiratory system
      decreased pulmonary gas exchange response to breathing resistance expiration.

PMID- 22420159
TI  - [Peculiarities of bile formation in rats of different sex under estron
      influence].
AB  - The influence of estron (8 microg/100g of animal's body weight) on the exocrine
      function of liver and the changes in bile acid composition of bile on different
      sex rats was studied. It was shown, that hormone at the applied dose, effected
      choleresis of female rats more effectively. Estron also caused different changes
      in bile composition. So, estron stimulated bile acid conjugation with taurine and
      glycin in female rat liver. Increasing of free and conjugated bile acid
      biosynthesis in male rats was observed.

PMID- 22420160
TI  - [Effect of streptozotocin-induced diabetes and transient global brain ischemia on
      apoptosis in the thymus of rats].
AB  - The influence of incomplete global ischemia-reperfusion of the brain on the
      activity of pro- and antiapoptotic processes in the thymocytes by the intensity
      of p53 and Bcl-2 - proteins expressions has been investigated. It has been shown
      that in the cortical zone of thymus of rats with a four-month diabetes, as well
      as in the control rats and rats with diabetes mellitus after brain ischemia, the
      antiapoptotic processes are dominated. In the medullar zone of the gland in rats
      with diabetes, complicated and uncomplicated with brain ischemia-reperfusion the
      antiapoptotic mechanisms predominate too, but to a lesser extent than in the
      cortical zone.

PMID- 22420161
TI  - [Effect of normobaric hyperoxia on the markers of bone tissue metabolism].
AB  - We studied the influencing of normobaric hyperoxia one hour daily during 14 and
      28 days on the bone metabolism for 3- and 12-monthly Wistar male-rats (n =80). It
      was shown, that breathed normobaric gas mixture with 90% O2 during 14 days
      significant reducing of C-terminal propeptides of type I collagen levels for 36%,
      an increasing piridinolin levels for 37% and concentration of C-terminal
      telopeptides of type I collagen for 8% in the blood serum. We found reliable
      decreasing the concentration ofpiridinolin levels for 27% in adult rats in the
      same conditions. The C-terminal propeptides of type I collagen levels did not
      change in any of the groups' research. We believe that 14 days normobaric
      hyperoxia (90%) in young animals accompanied by violation of collagen synthesis.
      The adult rats were more stable and had no changes after influence the two
      hyperoxia levels.

PMID- 22420162
TI  - [Effect of sodium succinate on oxidative stress in erythrocytes during physical
      loading].
AB  - On the basis of model experiments in vitro with application of sodium succinate
      which is the basic constituent of dietary supplementation "YantarIn-Sport",
      possibility of correction of the structurally-functional state of red blood cell
      membranes is well-proven. It is show that prooxidative-antioxidative balance in
      washed erythrocytes is normalized with the accumulation of recovered glutathione
      from 2.34 to 3.12 x 10(-12) mM in one erythrocyte, and their sorption ability
      (from 35.6 to 27.1% as well as red blood cells permeability (from 4.61 to 3.98
      conditional units) are decreased. In vivo research the positive influence of
      sodium succinate on descriptions of red blood cells of skilled sportsmen is
      confirmed, that is founding for application of succinic acid derivatives with the
      purpose of sporting anaemia' warning as well as improvement of microcirculation
      processes and increase of speed blood flow.

PMID- 22420163
TI  - [Effect of acidophilic multiprobiotic symbiter on pathological changes in bone
      periodontal tissue under hypo-acidic condition].
AB  - The omeprazole-induced hypoacidity leads to metabolic disorders in the bone
      periodontal tissue: a disbalance of NO-ergic system, activation of collagen and
      noncollagen proteins catabolism. We have shown that such disorders are corrected
      by a multiprobiotic of new generation -- symbiter acidophilic.

PMID- 22420164
TI  - [The reaction of human surface and inside body temperature to extreme
      hypothermia].
AB  - The dynamics of changes in the parameters of the surface and core body
      temperature under the systematic impact of ultra-low temperature is described in
      this article. As a source of ultra-low temperature was used (Cryo Therapy
      Chamber) Zimmer Medizin Systeme firm Zimmer Electromedizin (Germany) (-110
      degrees C). Surface and internal body temperature was measured by infrared
      thermometer immediately before visiting cryochamber and immediately after
      exiting. In the study conducted 47,464 measurements of body temperature. It was
      established that the internal temperature of the human body under the influence
      of ultra-low temperatures in the proposed mode of exposure remains constant, and
      the surface temperature of the body reduces by an average of 11.57 degrees C. The
      time frame stabilization of adaptive processes of thermoregulation under the
      systematic impact of ultra-low temperature was defined in the study.

PMID- 22420165
TI  - [Characteristics of electrocardiogram in Black Sea bottlenose dolphins (Tursiops
      truncatus) females].
AB  - Methods and technical devices to record ECG are developed. There've been studied
      ECG traits in sexually mature Black Sea bottlenose dolphin females kept in
      captivity. It's been shown that sick dolphins have tachycardia, heart rate
      disturbance, change in directivity of waves and their polarity and extrasystoles.

PMID- 22420166
TI  - [Structure and function of biomembranes: influence of nanoparticles].
AB  - The up-to-date view on a biomembrane structure and functions and the role of
      lipid, protein and carbohydrate biomembrane components in maintenance of a cell
      vital activity is summarized in this article. The up-to-date model of a
      biomembrane structure as a nanocompartmentalized fluid in which lipids and
      proteins undergo anomalous diffusion is examined. An attention is paid to lipid
      rafts existence as nanoscaled membrane domains. The analysis of literature and
      research results concerning the nanonature of ion channels and the mechanism of
      influence of nanoparticles on a biomembrane is carried out. It is shown that the
      data on structure and functions ofa biomembrane and the nature of influence of
      nanoparticles on it is necessary to create new high-performance therapeutic
      agents, diagnostic tools and to study nanoobjects' toxicological properties.

PMID- 22420167
TI  - [Blue bloater, pink puffer and other phenotypes of COPD].

PMID- 22420168
TI  - [Present and future in the use of anti-tubercular drugs].
AB  - After several decades without any notable progress, there are encouraging results
      in research and development of anti-TB drugs, the result of a large number of
      projects now in competition. Along with developing new drugs to treat
      tuberculosis (TMC207, SQ109, LL3858) are being reassessed others to optimize
      their effectiveness in order to shorten and simplify therapy (rifampin and
      rifapentine) and three other drugs, currently used for other indications, were
      forwarded towards TB (gatifloxacin and moxifloxacin, linezolid). Time to approval
      as a antiTB drug is 10-15 years, consisting of phases of preclinical and clinical
      research. Substitution of moxifloxacin for isoniazid during intensive phase
      treatment of pulmonary tuberculosis resulted in a small but statistically
      nonsignificant increase in 8th- week culture negativity. TMC207, a
      diarylquinoline with a unique way to address Mycobacterial ATP synthetase, shows
      high activity in vitro against Mycobacterial strains sensitive or resistant to
      all drugs in the first and second line, including fluoroquinolones, demonstrating
      exceptional qualities in vivo against several species of mycobacteria, in various
      animal models. TMC207 was added to a basic standard regimen in a study of MDR-TB
      patients. After two months and satisfactory tolerability, sputum conversion rate
      in culture was 48% (versus 9% in the placebo group). Two nitroimidazole (PA-824
      and OPC-67683) are currently in clinical development. PA-824 demonstrated good
      safety and tolerability in adult patients with pulmonary TB in South Africa, when
      given once daily for 7 days. Associating isoniazid, would prevent the selection
      of mutants resistant to Isoniazid. Linezolid 600 mg is currently being tested in
      a Phase II for treatment of XDR-TB in the Republic of Korea. PNU-100480,
      analogous to the previous one, has the potential to significantly shorten the
      treatment in cases where there is sensitivity and in those with resistance to
      drugs. 300 mg dose is under investigation in a phase II pilot study in MDR-TB in
      South Africa. With this interest and commitment, it appears that there is a
      chance of having a new drug available soon.

PMID- 22420169
TI  - [Sleep apnea syndrome -- cause of resistance to treatment of arterial
      hypertension].
AB  - The prevalence of sleep apnea syndrome is relatively high in population (5%). The
      mortality is significantly higher in those with apnea-hypopnea index >20. There
      is an increased rate of car accidents in the subjects with OSA compared to those
      who don't have this syndrome (31% versus 6%). The impact of OSA on mortality is
      also given by its association with a significant number of cardiovascular
      diseases. The association between OSA and hypertension has been much debated. The
      prevalence of hypertension among patients with OSA varies between 50-58%, while
      the prevalence of OSA in hypertensive patients is 30%. A particular association
      is OSA and resistant hypertension, i.e. blood pressure that remains above goal in
      spite of the concurrent use of three antihypertensive agents of different
      classes, one to be a diuretic and all pharmacological agents being prescribed at
      recommended doses. Secondary causes of hypertension are common in patients with
      resistant hypertension. Among these causes, one of the most frequent is sleep
      apnea syndrome. Some of the mechanisms by which sleep apnea contributes to the
      development of hypertension are intermittent hypoxia and/or increased upper
      airway resistance associated with sleep apnea that induces a sustained increase
      in sympathetic nervous system activity. Treatment of sleep apnea with continuous
      positive airway pressure devices (CPAP) improves blood pressure control, although
      the benefit of CPAP evaluated in clinical trials is variable.

PMID- 22420170
TI  - Deletion allele of the ACE gene is not a risk factor for asthma predisposition.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) has an important role in
      inactivation of bradykinin and tachykinins which known as powerful
      bronchoconstrictors. It has been demonstrated that an insertion (1)/deletion (D)
      genetic variations within the ACE gene greatly influence the plasma level of ACE.
      OBJECTIVE: The aim of the present study was to determine the frequencies of ACE D
      and I alleles and ACE DD, DI and II genotypes in asthmatic patients and controls
      with Iranian Azeri-Turkish origin and to compare the frequency of the ACE
      genotypes between asthmatic patients and controls. METHODS: We genotyped 212
      healthy controls including 73 males and 138 females, as well as 62 patients with
      asthma, including 28 males and 34 females by PCR. RESULTS: Of the 212 healthy
      controls: 1) the prevalence of DD, DI, and II genotypes were 83(39.151),
      92(43.396) and 37(17.453), respectively. 2) the frequency (%) was 257(60.9)for D
      allele and 165(39.1 )for II allele. 3) D and II allele frequencies were 0.61 and
      0.39 respectively. Of the 62 patients with asthma: 1) the prevalence of DD, II,
      and III genotypes were 17(27.42), 31(50) and 14(22.58), respectively. 2) the
      frequency (%) was 65(52.42)for D allele and 59(47.58 ) for II allele. 3) D and II
      allele frequencies were 0.52 and 0.48 respectively. Statistical analysis showed
      that studied groups (female + male patients group and female + male controls
      group) were in Hardy-Weinberg equilibrium. Our findings imply that II/D ratio was
      0.61/0.39 in all controls and 0.6/0.4 in male or female controls. Significant
      differences were not found in the ACE genotype or allele frequencies between
      studied groups regarding all cases versus all controls, female cases versus
      female controls, male cases versus male controls. CONCLUSION: We have concluded
      that deletion allele of the ACE gene is not a risk factor for asthma
      predisposition.

PMID- 22420171
TI  - Reproductibility of cardiac monitoring in men using impedance cardiography during
      Mueller maneuver.
AB  - Obstructive sleep apnea hypopnea syndrome (OSAHS) is a form of sleep-disordered
      breathing highlighted by recurrent episodes of upper airway collapse during
      sleep. OSAHS contributes to an increased risk of cardiac arrhythmias,
      cardiovascular disease, and altered immune function. Measuring cardiac function
      in OSAHS patients can provide information that can help delineate clinical
      treatment efficacy. Cardiac function has been widely tested using electrical
      bioimpedance. AIM: The aim of this study was to determine the reproducibility of
      cardiac functional parameters in subjects performing Mueller maneuver. METHODS:
      Fifteen apparently healthy males were tested on three different days in a
      protocol requiring their performance of forced and sustained inspiratory efforts
      against a closed epiglottis (Mueller maneuver-MM). On each day, the protocol
      included performance of two simulated apneas of 30 seconds, with at least 3
      minutes of normal breathing in between. RESULTS: Changes from a normal breathing
      baseline for cardiac output, heart rate and stroke volume were comparable during
      both MM in all three days. The coefficient of variation was similar on all three
      trials. CONCLUSIONS: This new contemporary bioimpedance cardiography device
      provided reliable measures of dynamic cardiac responses during a simulated apnea
      event.

PMID- 22420172
TI  - Body position and breathing abnormalities during sleep: a systematic study.
AB  - BACKGROUND: Until now, studies about body position and nocturnal breathing
      abnormalities have been restricted to comparing supine versus lateral positions.
      OBJECTIVES: In this retrospective study, we systematically evaluated the effect
      of body position on nocturnal breathing in 105 patients with a sleep apnea
      hypopnea syndrome (SAHS). METHODS: All the patients had an apnea hypopnea index >
      10/h, as judged from polysomnography performed in the sleep laboratory. A
      thoracic sensor allowed to detect nine distinct body positions: supine (S),
      supine right (SR), right (R), prone right (PR), prone (P), prone left (PL), left
      (L), supine left (SL) and sitting upward (UP). Respiratory variables (number of
      obstructive, central and mixed apneas, of hypopneas and of desaturations, all
      expressed as an index per hour of total sleep time) were evaluated versus the
      body positions, using the non-parametric Kruskal-Wallis H method. Pairwise
      comparisons were performed using Mann-Whitney U tests. RESULTS: Most of the total
      sleep time (45%) was spent supine. A significant effect of body position was
      found for all the respiratory variables. Breathing was better in the intermediate
      SR and SL positions than S, and also better in PR and PL positions than,
      respectively, R and L. All the respiratory variables gradually improved when
      gradualling moving from the S to the P position. CONCLUSIONS: A nine position
      sensor, able to define intermediate positions in addition to the basic cardinal
      positions, is useful in the sleep laboratory. Using such a sensor, we found in
      SAHS patients that nocturnal breathing improves as a continuum from the S to the
      P position.

PMID- 22420173
TI  - Rare form of semi-invasive aspergillosis in immunocompetent patient: case report.
AB  - Chronic necrotizing or semi-invasive aspergillosis represents a disease commonly
      occurred in patients with mild immunodeficiency. We report a case of chronic
      necrotizing pulmonary aspergillosis in immunocompetent patient without underlying
      disease. The discovery of the disease was made accidentally, by finding a nodular
      opacity on a routine chest X-ray. The diagnostic was confirmed by pathological
      and bacteriological examination. With specific antifungal treatment, no complete
      eradication was obtained and the patient has a slow evolution with many relapses.

PMID- 22420174
TI  - [Sleeve resection of right main bronchus for posttraumatic bronchial stenosis].
AB  - INTRODUCTION: Tracheobronchial disruption is one of the most severe injuries
      caused by blunt chest trauma. A high index of clinical suspicion and accurate
      interpretation of radiological findings are necessary for prompt surgical
      intervention with primary repair of the airway. Delays in treatment increases the
      risk of partial to complete bronchial stenosis. CASE REPORT: A 21 years old male
      was admitted to our hospital following a workplace accident. A chest radiograph
      showed bilateral pneumothorax, cephalic and mediastinal emphysema. Chest tubes
      were placed on each side, with full pulmonary expansion and remission of
      emphysema. Minimal lesions of the right main bronchus were found at fiberoptic
      bronchoscopy. Daily chest X-rays showed an uncomplicated recovery. A stenosis was
      suspected due to right lung pneumonia evolving under specific antibiotherapy.
      Right main bronchus posttraumatic stricture was diagnosed by fiberoptic
      bronchoscopy. He underwent a right lateral thoracotomy with sleeve resection of
      stenotic bronchi. Control bronchoscopy reveals main bronchus widely patent with
      untraceable suture line. DISCUSSION: Main bronchus rupture in blunt chest trauma
      is an additive effect of chest wall compression between two solid surfaces,
      traction on the carina and sudden increase in intraluminal pressure. Symptoms may
      vary: soft air leak, pneumothorax or limited mediastinal emphysema. Bronchoscopy
      should be performed immediately or when available. Granulation tissue leads to
      progressive bronchial obstruction, with distal infection and permanent
      parenchymal damage. Sleeve resection of the stenosed segment is the treatment of
      choice and restores fully the lung function. CONCLUSION: Rupture of main bronchus
      is a complication of blunt chest trauma. Flexible bronchoscopy is useful and
      reliable for early diagnosis of traumatic tracheobronchial injuries. Delayed
      diagnosis can lead to lung parenchyma alteration due to retrostenotic pneumonia.
      Resection and end-to-end anastomosis is the key of successful in these cases.

PMID- 22420175
TI  - [Smoking prevention. Forbidding the inscriptions on cigarette packs -- a possible
      revolution in the field].

PMID- 22420176
TI  - [Early results of congenital clubfoot using Ponseti method].
AB  - Congenital clubfoot is one of the most common congenital skeletal defects. Its
      aetiology remains unclear. Due to its high incidence and social consequences, the
      therapy of congenital clubfoot presents an important medical issue. Non-surgical
      treatment methods are preferred. Many publications confirmed the efficacy of the
      Ponseti method. The aim of this study was to present early results of congenital
      clubfoot treatment using the Ponseti method in a one-year follow-up. The therapy
      protocol was in accordance with guidelines presented by the inventor. The
      necessity of surgical treatment was a criterion for negative treatment outcome.
      One hundred and sixteen feet of 92 children were analysed. A Dimeglio-Bensahel
      classification was used for the evaluation of the defect advance. Seventy-one
      feet (61.2%) were assessed as grade II, 43 feet as grade III (37.1%) and 2 feet
      as grade IV deformation. No patients with grade I deformation were included into
      the study. A positive treatment outcome was observed for 96 feet (82.7%), whereas
      a negative result for the remaining 20 feet (17.3%). Our results are therefore
      not consistent with the literature data. It could have resulted from the too
      precipitate qualification for surgery by the physician and problems with
      compliance. The Ponseti method is an effective and less straining treatment
      modality of the congenital clubfoot. In most cases it allows for avoiding
      extensive surgery and associated complications. A necessity of wearing an
      orthosis and a risk treatment failure, if not worn systematically, should be
      emphasised. A longer follow-up period is required for complete result analysis.

PMID- 22420177
TI  - [Congenital talipes equinovarus--family occurrence].
AB  - Although congenital talipes equinovarus (CTEV) is one of the most frequently
      occurring congenital defects of locomotor organs, its ethiopathogenesis is still
      not fully known. Amongst the others, the inheritance patterns of that defect are
      not fully known, and that restricts genetic therapeutics and development of new
      treatment technologies. The aim of this study was analysis of family lineages of
      205 children with CTEV (298 feet) treated at our centre in the years 1998-2008.
      The family occurrence of CTEV was found in 16 cases (8% of analysed group). 6
      lineages, in which CTEV occurred in successive generations, were analysed in
      detail. Particularly interesting is the lineage of the family 1, in which the
      defect occurred in three successive generations. In case of that family, an
      autosomal dominant inheritance pattern is possible. Previously that pattern of
      CTEV inheritance was described only for isolated populations of Polynesians. In
      own material the family occurrence of CTEV was found to be less frequent than in
      bibliographic references. The defect occurred twice as often in boys, while the
      severe form was more frequently observed in girls, and that is consisted with
      data in the available bibliography. The analysis of presented lineages of
      families with CTEV did not allow unambiguous defining of the inheritance pattern
      for that defect. To confirm the autosomal dominant pattern of CTEV inheritance in
      the family in which the defect occurred in three successive generations, genetic
      tests would be necessary.

PMID- 22420178
TI  - [Kayakers' length of training period lumbar segment mobility and weak links
      occurrence in biokinematics chain].
AB  - INTRODUCTION: Strength shaping in canoeists can cause limitation of spine
      movement and pain symptoms. Because of the problem's importance the following
      study has been undertaken: in order to: 1) determine the relationship between the
      range of lumbar spine mobility and training experience in kayaking; 2) estimate
      of the relationship between the occurrence of weak links and symptoms of pain and
      range of motion in the lumbar spine. MATERIAL AND METHODS: 25 Walcz SMS players
      were examined, including 8 female kayakers, 8 canoeists and 9 canadians. Age (M
      +/- SD) 15.60 +/- 1.04 years; training period 5.64 +/- 1.78 years. Low threshold
      Performance Matrix. tests were used. to assess the presence of a weak connection
      The participants determined the sensation of pain in the lumbar spine (LBP) on a
      numeric scale. Mobility in the lumbar spine was rated by electrogoniametrics
      method. The results were statistically analyzed using analysis of variance ANOVA,
      Tukey's t tests and linear regression analysis. RESULTS: In all examined players
      weak connection in the lumbar spine were found in the direction of flexion,
      rotation and lateral flexion, and there were no weak links in the direction of
      extension. Only 10 players did not suffer from LBP. The other declared the
      existence of these symptoms. It has been found that the length of training period
      in kayaking is associated with reduced mobility in the lumbar spine and the
      occurrence of weak links. As a result pain symptoms have often occurred. Gender
      and specialization have no influence on the frequency and Range of LBP symptoms
      in kayaking. CONCLUSIONS: 1) Sports training in kayaking causes reduced mobility
      of the lumbar spine and may cause weak links in the chain of biokinenatics
      connections and symptoms of LBP. 2) Gender and sports specialization does not
      differentiate canoeists because of LBP symptoms. The reasons for their occurrence
      can be ascribed to the use of weight training.

PMID- 22420179
TI  - [Roentgenometric assessment of spine shape in patients with a flexion contracture
      of hip as a consequence of hip osteoarthrosis].
AB  - OBJECTIVE: Current knowledge on influence of hip arthrosis on shape of the lumbar
      spine is insufficient. Also universal method of roentgenometric assessment of
      lumbar spine is not yet accepted. The aim of this study was the evaluation of
      influence of the degree of hip arthrosis on the shape of the spine in a sagittal
      plane measured by means of selected, roentgenometric parameters. MATERIALS AND
      METHODS: The study group consisted of 120 patients with hip osteoarthrosis,
      including 64 women and 56 men. Average age was 69.5 (range from 41 to 81 years).
      The analysis focused on the influence of age, flexion contracture and
      radiological degree of arthrosis on selected roentgenometric parameters of lumbar
      lordosis in the upright and supine positions: Fergusson angle (F), total lordosis
      angle (Th12-S1), lower lordosis angle (L3-L4/L5-S1), upper lordosis angle (L1
      L2/L3-L4). RESULTS: Correlation index between flexion contracture of the hip and
      total lordosis angle calculated in the upright and supine positions amounted to
      0.627 (p < 0.0001) to 0.554 (p < 0.0001) respectively. For the Fergusson's angle
      correlation index ranged between 0.879 (p <0.001) to 0.758 (p <0.0001)
      respectively. Differences between average values of individual parameters in
      groups with varying degrees of arthrosis ranging at the significance level from p
      <0.0001 for total lordosis angle and Fergusson angle top < 0.04 for lower
      lordosis angle prove the interdependence between the degree of lumbar lordosis of
      the spine and hip joint osteoarthrosis. CONCLUSIONS: The Fergusson angle and
      total lordosis angle of Th12-S1 are the most sensitive roentgenometric parameters
      to the severity the hip arthrosis represented by it's flexion contracture.

PMID- 22420180
TI  - [Complications after intramedullary nailing of the tibia].
AB  - As demonstrated by the experience, treatment of fractures of the tibial
      intramedullary nail proved to be the most advantageous method of operating as:
      put the rod runs in the biomechanical axis of the limb, is inside of the bone, is
      a minimally invasive procedure (carried out with small cuts). Initially, the
      method of intramedullary nailing was used for the treatment of fractures of the
      shaft center of the tibia. However, the development of surgical techniques has
      meant that the method can also be used to treat fractures of the proximal and
      distal tibia. The most common complications of surgical treatment by this method,
      apart from infection include: changing the limb axis, rotation of the factions
      against each other, and degenerative changes in the knee depend on the
      introduction of nail art. The aim of this study is to analyze in order to treat
      patients with lower leg fractures using intramedullary nailing. It was carried
      out based on the collected medical records and clinical examination, which
      included 45 patients. It was found that the most common complication observed
      after treatment was varus tibial fragments (5 cases - 11% of respondents). Less
      commonly observed disorder in the form of the axis of rotation of the limb (1
      case) and anteflexion -1 case. During the test showed that the axis of the limb
      abnormalities were associated with the initial surgery. There was no significant
      progression of the axis of the limb abnormalities in the period from the date of
      surgery to complete primary union. Complications in the form of secondary
      osteoarthritis of the knee reported in studies of other authors, did not occur in
      any of the analyzed in the work cases.

PMID- 22420181
TI  - [Early results of revision hip arthroplasty using modular Restoration stem].
AB  - There is an increasing number of hip joint arthroplasty procedures all over the
      world which are followed by revision surgery. The cases of severe bone loss and
      periprosthetic fractures revision of a stem can constitue a serious challenge
      even for an experienced orthopedic surgeon. MATERIAL: In the research material
      there are 18 patients 6-50 months after the stem of the hip prosthesis revision
      with Stryker Restoration modular stem. METHODS: Clinical evaluation according to
      HHS protocol, the quality of life measured with SF-36 form, and physical activity
      evaluated using UCLA score. The methods are also AP and X-Ray of both hips and
      lateral X-ray of revised hip with osteolysis around stem, stem subsidence, and
      difference in leg length evaluation, as well as the comparison of hip offsets.
      RESULTS: Mean HHS score was 78.6 pts, mean SF-36 based quality of life 50.5 pts,
      and the mean UCLA 4.72. Radiolucent zones around the stem were observed in
      several cases which were correlated with the stem subsidence. CONCLUSION: The
      clinical results in this study are similar to those from the literature, and
      slightly lower than of the patients after primary hip arthroplasty, particularly
      in function measuring subscales. The quality of life scores of our patients was
      significantly lower than reported by other authors in cases of hip revision
      arthroplasty. There was no case of aseptic loosening. Further observation of the
      patients considering osteolysis and its relation to stem subsidence is needed.

PMID- 22420182
TI  - [Treatment of open femur fracture with critical bone loss of femoral shaft in
      politrauma patient--case report].
AB  - The authors describe the case of a 21 year old patient who suffered an politrauma
      injury in a traffic accident (motorcyclist). OBJECTIVES: Presentation of
      possiblities of treatment femur bone fracture with critical bone loss using
      intramedullary nail. METHODS: Patients's Injury included: fractures of the femur,
      temporal bone, and ulna. The patient's Severity Score (ISS) was 24. The dominant
      trauma fracture was open, comminuted fracture of femur shaft (AO 32-C2, Anderson
      Gustilo IIIa) with bone loss stated as critical (loss of femoral shaft over 10
      cm, including the loss of more than 50% of the circumference was about 8 cm
      length, and the loss of the full circumference of more than two branches of the
      missing bone). Osteosynthesisnad bone length reconstruction of the femur was with
      use of intramedullary locking nail. RESULTS: Full reconstruction was regenerated
      after 12 months. Although there was extensive injury no local and general
      complications appeared. CONCLUSION: Early definitive fracture stabilization and
      secondary dynamisation possible to obtain the bone regeneration at the defect
      site.

PMID- 22420183
TI  - [Obturator dislocation--a rare complication of the total hip prosthesis. Case
      study].
AB  - The article presents the case of a 55-year-old patient with an injury of the
      right leg, which was due to a falling lightly at her buttocks during squatting.
      Patient was transferred to hospital with complaints of severe pain and limited
      motion in her right hip. In view of the patient's clinical status and following
      radiological diagnostic work-up, she was diagnosed with femoral neck fractures,
      the decision was made to perform a primary total hip arthroplasty (THA) using an
      lateral approach in the lateral decubitus position. A good clinical and
      radiological outcome was achieved. Patient after 12 days without complications
      was released home. After 4 days being home she was transferred to hospital again
      with complaints of severe pain and limited motion in her operated hip. On
      admission, her right lower leg was lying in an extremely rotated and abducted
      position. However, the extremity was neurologically intact with good pedal
      pulses. Physical examination and an initial anteroposterior radiograph showed
      obturator dislocation of the hip prosthesis. The decision was made to perform an
      open reduction. The operative problem in this particular case was removing the
      head of the prosthesis from the obturator foramen without making any jatrogenic
      harm.

PMID- 22420184
TI  - Method of the nerve root selection in diagnostic and therapeutic process in
      patients with multilevel nerves entrapment in lumbar spine due to the
      degenerative process.
AB  - This paper presents a method for determining the proper diagnostic techniques and
      the respective therapy in patients affected with nerve root compression in the
      lumbar region of the spine based on developing an algorithm that attempts to
      assess the level of compression and determine the afflicted nerve root. The
      clinical picture of degenerative disease of the lumbar spine is characterized by
      symptoms related to the affected nerve root. The diagnosis and respective therapy
      benefits from the use of minimally invasive techniques, such as selective root
      blocks or use of the radiofrequency. For instance, with changes on many levels it
      is necessary to comply with the rules for the selection of the correct nerve
      roots so there can be referral for proper treatment. The method of selection is
      dependent on the correlation of the results of the clinical examination, as well
      as secondary diagnostic studies, of which the gold standard is the MRI. In
      clinical practice we rely on the results of magnetic resonance imaging to
      determine the nerve root level in the lumbar spine. This allows the
      classification of the roots in relation to the frequency of compression
      occurrence along its course. The morphologic changes resulting in a similar
      clinical picture may indirectly suggest a degree of exacerbated risk. In
      addition, we suggest a system of describing the MRI scans, which allows us to
      retrospectively obtain information on the locations of potential compression of
      nerve roots.

PMID- 22420185
TI  - Three point crutch gait from the perspective of biomechanics and kinesiology.
      State of knowledge and idea behind the research.
AB  - The study characterizes the idea behind the research project which consists in
      biomechanical and kinesiological analysis of three point crutch gait. The
      structure of the study is in part similar to an earlier publication of the
      authors [1], which discussed swing through gait. By defining the three point
      crutch gait and describing its general kinematic structure as well as
      synthetically analyzing the state of knowledge, the authors formulated the
      purpose of the study, the adopted research model - including the description of
      the modern and integrated measurement systems that were used and which consisted
      of: 2 AMTI force plates integrated into a measurement walkway, a set of 6
      optoelectronic cameras of the BTS System as well as a multichannel kinesiological
      electromyography performed with the use of the NORAXON System. All phases of the
      research were characterized, presenting the adopted research protocol in its
      entirety.

PMID- 22420186
TI  - [Prophylaxis of venous thromboembolism in patients with chronic obstructive
      pulmonary disease].
AB  - At present, almost 25% of the world population suffer from venous thromboembolism
      (VTE). This condition is currently regarded as a continuum of thromboembolism of
      pulmonary artery (TEPA) and venous thromboses including superficial venous
      thromboses. These diseases are not infrequently concomitant and asymptomatic. Up
      to 75% of the cases of venous thrombosis in the lower extremities are associated
      with latent TEPA and 80% of the cases of pulmonory embolism with asymptomatic
      venous thrombosis. The mortality rate from TEPA is estimated to be one person per
      1,000. The data of autopsies indicate that 50-80% of the TEPA cases are not
      diagnosed at all. As many as 300 subjects of 100,000 suffer trophic ulcers in the
      lower extremities as a result of previous venous thrombosis. Prophylaxis is
      supposed to be the principal means of VTE control. Chronic lung diseases are the
      leading risk factors of VTE. Chronic obstructive pulmonary disease (COPD) is a
      major cause of morbidity and mortality throughout the world. It is expected to
      become the third major cause of death by 2020. Hospitalization of COPD patients
      in therapeutic clinics increases the risk of VTE by 7.98 times. Prophylaxis of
      VTE in COPD patients may reduce the frequency of exacerbation and hospitalization
      and increase life expectancy.

PMID- 22420187
TI  - [Mechanisms of development of osteoporosis in patients with chronic obstructive
      pulmonary disease].
AB  - Chronic obstructive pulmonary disease (COPD) is the leading chronic pulmonary
      pathology and its systemic manifestations, such as the loss of muscular mass,
      connective tissue dysplasia, and osteoporosis (OP), have recently drawn
      increasingly more attention. The inflammatory process during COPD is underlain by
      disbalance between pro- and anti-inflammatory cytokines. As a rule, cytokines act
      as local regulators but become systemic agents when their production and
      concentration in blood increase during intense and long-standing inflammatory
      processes. Proinflammatory cytokines induce OP while anti-inflammatory ones
      prevent its development. As known, there are many modifiable and non-modifiable
      (e.g. iatrogenic) risk factors influencing OP pathogenesis. Both iatrogenic and
      primary pathophysiological mechanisms are responsible for the development of
      osteopenic syndrome during COPD. The leading cause in pathogenesis of reduced
      mineral bone density (MBD) and disturbed osseous metabolism is disbalanced
      cytokine production resulting from chronic inflannation, oxidative stress, and
      increasing tissue hypoxia and hypercapnia. An additional contribution to the
      development of pulmogenic osteopenia comes from the body mass deficit, myopathy,
      organic physical activity, and smoking. A wealth of current publications suggest
      the importance of body mass loss during COPD. Domestic and especially foreign
      authors emphasize that pathogenesis of OP in patients with COPD remains poorly
      known. Long-term studies and methods for early diagnostics of this condition are
      needed to resolve the problem.

PMID- 22420188
TI  - [Laboratory and instrumental diagnostics of pancreatic diseases].
AB  - The review focuses on the potential of modern laboratory and instrumental
      diagnostics ofpancreatic diseases including various forms of chronic
      pancreatitis, pancreatic cancer, cysts and pseudocysts, calcificators and
      concrements, abscesses, neuroendocrine tumours, etc. Diagnostic criteria for
      exocrine pancreatic disorders, such as hyper- and hyposecretory (hyper- and
      hypoenzymatic) forms of chronic pancreatitis are described along with direct and
      indirect, invasive and non-invasive, probe-based and probe-free methods for their
      study. Special attention is given to instrumental visualization of structural and
      morphological changes in the pancreas under different pathological conditions.
      The description of methods for the study of pancreatic endocrine functions and
      diagnostics of pancreatic diseases is preceded by a brief anatomo-physiologic
      essay.

PMID- 22420189
TI  - [The role of psychosocial risk factors in evolvement and progression of coronary
      heart disease].
AB  - The authors present the currently available data on the socioeconomic status,
      social isolation, social support, and associated personality changes considered
      to be risk factors of coronary heart disease (CHD). In addition, socioeconomic
      conditions of the family during the patient's childhood contributing to the
      evolvement and progression of CHD are reviewed. Information is provided about the
      role of combination of common somatic risk factors of CHD and socio-psychologic
      peculiarities of the patients in the development of CHD.

PMID- 22420190
TI  - [Modern approaches to estimating the severity of community-acquired pneumonia].
AB  - Adequate evaluation of the severity of pneumonia is paramount for the choice of
      therapy, prescription of efficacious empiric antibacterial treatment, and timely
      initiation of intensive hemodynamic and respiratory support. To-day, a number of
      assessment scales for estimation of clinical conditions of patients with
      pneumonia are available, each having its merits and demerits. The present paper
      analyses modern recommendations on the treatment of severe community-acquired
      pneumonia.

PMID- 22420191
TI  - [Results of treatment of patients with acute myocardial infarction and high risk
      of cardiac complications].
AB  - The authors compare the results of the treatment of 883 patients with acute
      myocardial infarction (AMI) referred to the group with high risk of cardiac
      complications based on the TIMI, GRACE, and TIMI Il assessment stratification
      scales. 487 patients were treated by conservative therapy using anticoagulative
      (n = 414) or thrombolytic (n = 73)) agents. 396 underwent surgical treatment
      (coronary artery bypass surgery (101) or percutaneous coronary angioplasty
      (295)). The mortality rate in the group treated by percutaneous coronary
      angioplasty was 13.6 (p < 0.001), 7.2 (p < < 0.01) and 3.5 (p < 0.05) times lower
      than after anticoagulation therapy, thrombolysis and coronary bypass surgery
      respectively. It is concluded that percutaneous coronary angioplasty has
      advantages over other modalities for the treatment of patients with acute
      myocardial infarction and high risk of cardiac complications.

PMID- 22420192
TI  - [Peculiarities of cardiac contractile function in patients with arterial
      hypertension depending on temperament and anxiety state].
AB  - The aim of the work was to elucidate the relationship between temperament and
      personal anxiety and between left ventricular myocardium hypertrophy,
      contractility and diastolic function in 671 men (mean age 54 +/- 1.8 yr) with
      newly diagnosed grade II arterial hypertension who took no antihypertensive drugs
      before the study. The tone of vegetative nervous system, serum levels of
      cortisol, aldosterone, thyroxin, and insulin were measured. EchoCG was used to
      determine left ventricular myocardium mass (LVMM), LVMM index, the ratio of
      transmitral blood flow at the beginning and end of diastole, left ventricular
      ejection and shortening fractions, end-systolic and diastolic size and volume.
      Phlegmatic and melancholic patients differed from cholerics and sanguinics in the
      predominance of parasympathetic influences, elevated blood aldosterone and
      insulin levels in combination with higher LVMM and LVMM index but lower left
      ventricular systolic and diastolic function. These characteristics were
      especially well apparent in anxious subjects comprising a risk group for cardiac
      insufficiency.

PMID- 22420193
TI  - [Possibilities of rehabilitation of patients with chronic cardiac insufficiency
      in the earlier period after an episode of decompensation].
AB  - The authors analyse the possibility and safety of including patients in a
      cardiorehabilitation program in the earlier period after an episode of
      decompensation of chronic cardiac insufficiency (CCI). The influence of a short
      term course of interval training on tolerability of physical exercises and
      quality of life was estimated in 162 patients with CCI hospitalized for the
      treatment of decompensation. 125 (77.2%) of them did not meet the criteria for
      inclusion in the rehabilitation program, the main causes being moderate or severe
      aortic stenosis, orthopedic or neurologic restrictions. 19 of the 32 patients
      included in the program participated in the three-week training course but only
      15 (78.9%) completed it. The increment of peak oxygen consumption averaged 23
      ml/kg/min (17.4%).

PMID- 22420194
TI  - [Relationship between insulin, leptin, and melatonin contents in patients with
      metabolic syndrome].
AB  - Melatonin, leptin, and insulin secretion was studied in 25 men with metabolic
      syndrome (MS) verified against IDF criteria (2005) (mean age 44 +/- 2 yr). The
      control group was constituted by 23 healthy men (mean age 45.1 yr). Melatonin
      secretion was estimated from 6-oxymelatonin sulfate (6-OMS) level in urine
      samples collected at 4 a.m. (in the darkness). It was shown to increase at this
      time in both groups but was lower in MS patients than in controls (t = 2, p <
      0.05). The Pearson correlation analysis revealed moderate negative correlation
      between 6-SOMT level in urine and insulin and glucose levels in plasma (r =
      0.95). Peak 6-SOMT level showed strong negative correlation with the leptin
      level. Multiple regression analysis demonstrated strong linear relationship of 6
      OMS and insulin levels (r = 0.93) and 6SOMT and leptin levels (r = 0.95). The
      calculated odds ratio suggests that the risk of insulin resistance in patients
      displaying a peakless melatonin secretion profile is 3 times that in control
      subjects (OR = 3.0; 95% CI = 1.3-7). It is concluded that patients with MS
      present with disturbances of melatonin secretion manifest as the absence of its
      physiological elevation at night hours; they are characterized by negative
      correlation between melatonin, leptin and insulin levels and changes in melatonin
      secretion in relation to abnormal production of insulin and leptin.

PMID- 22420195
TI  - [Gastric secretory function in psoriatic patients with chronic opistorchosis
      before and after antihelminthic therapy].
AB  - The aim of the work was to study secretory function of the stomach in psoriatic
      patients with chronic opistorchosis (CO) before and after antihelminthic therapy.
      It included 90 such patients, 70 with psoriasis alone, 70 with CO, and 30 healthy
      subjects. All patients were examined by oesophagogastroduodenoscopy. Fractional
      gastric secretion was measured. The secretory function of the stomach was most
      seriously disturbed in psoriatic patients with CO. It did not further deteriorate
      after antihelminthic therapy. The disturbance was associated with reduced
      hydrochloric acid and pepsin levels which confirms the necessity of
      antihelminthic therapy.

PMID- 22420196
TI  - [The relationship between extraesophageal manifestations of gastroesophageal
      reflux disease, the frequency of heartburn and severity of oesophagitis].
AB  - We performed clinico-epidemiologic screening for the heartburn in a
      representative sample from a total of 1138 subjects and for oesophagitis from 371
      ones. In a separate study 120 patients were divided into groups differing in the
      severity of oesophagitis based on the Savary-Miller classification. The
      extraesophageal manifestations were diagnosed by clinical and instrumental
      methods. The close relationship of these manifestations with heartburn and
      oesophagitis was more pronounced in men than in women. Enhanced severity of the
      lesions in eosophageal mucosa in patients with oesophagitis was related to
      increased frequency of ENT diseases and cardialgia but not respiratory disorders.
      The data obtained give evidence of direct association of heartburn and
      eosophagitis with coughing, ENT diseases and cardialgia.

PMID- 22420197
TI  - [Methods for the prevention and treatment of toxico-hypoxic encephalopathy in
      patients with acute severe poisoning].
AB  - The study included 147 patients with toxico-hypoxic encephalopathy resulting from
      acute poisoning. It was shown that intensive therapy with cytoflavin (20 ml in
      400 ml of 5% glucose solution twice daily for 7 days) reduced severity of hypoxic
      brain lesions and suppression of CNS as apparent from the improvement of its
      bioelectric activity. The recovery of CNS regulatory action on the life
      sustaining systems of the body promoted normalization of the respiratory
      component of oxygen transport. The improvement of the patients' conditions in the
      acute phase contributed to accelerated recovery of cognitive-amnestic functions
      and social adaptation. Cytoflavin therapy improved the clinical picture of toxico
      hypoxic encephalopathy due to the reduction in the duration of the comatose state
      from 45.3 +/- 8.2 to 27.7 +/- 6.9 hr and the decrease in the frequency of
      secondary pulmonary complications from 72.7 to 35.9%.

PMID- 22420198
TI  - [Early effects of enalapril in patients with chronic cerebral ischemia and
      arterial hypertension].
AB  - The study included 56 patients with chronic cerebral ischemia and arterial
      hypertension. Protective effect of enalapril (enap) on endothelium was apparent
      as increased fibrinolytic activity of plasma, decreased platelet aggregation
      amplitude caused by adrenalin and ristocetin, partial restoration of endothelium
      dependent vasodilation, and inhibition of Willebrand factor release in the
      arteriovenous occlusion test. The degree of reduction of neurologic deficit by
      enalapril correlated with the decrease in Willebrand factor release.

PMID- 22420199
TI  - [How to help a "problem" patient].
AB  - A patient may become a "problem" owing to three groups of causes acting either
      independently or together. Group 1 is characteristic features of the patient
      including psychological problems and borderline psychiatric disorders. Group 2 is
      related to the physician's activity (overfatigue, poor communicative skills,
      etc.). Group 3 is comprised by the causes related to the peculiarities of the
      healthcare system structure and organization (overworked physicians, insufficient
      time that they can spend in direct care to an individual patient, inadequate
      information the patients acquire from non-medical sources). Poor organization of
      work in an outpatient facility inevitably deteriorates the quality of the
      provided care. The patients attending it begin making complaints against the
      personnel which leads to conflicts even in the absence of serious medical errors.
      Practical recommendations are proposed designed to help the "problem patients" to
      obtain quality medical aid and avoid conflict situations.

PMID- 22420200
TI  - [Scientific therapeutic schools: on certain debatable aspects of the traditional
      doctrine].

PMID- 22420201
TI  - [Sergey Sergeevich Yudin (on the occasion of his 120th birthday anniversary)].

PMID- 22420202
TI  - [The 90th anniversary of the Department of Infectious Diseases, St. Petersburg
      State Medical Academy].

PMID- 22420203
TI  - [Diagnosis of odontogenic maxillary sinusitis by spiral computed tomography using
      a dental program].
AB  - Genyantrum mucosal changes and the upper jaw ridge were analyzed in different
      forms of periodontitis and in cases of endodontic treatment failure with the
      dental filling material being in maxillary sinus cavity. Spiral computed
      tomography using the Denta Scan software could confirm the odontogenic nature of
      the changes found in 57 (85.0%) patients with suspected maxillary sinusitis.

PMID- 22420204
TI  - [Efficiency of medical versus endovascular treatment using drug-eluting stents in
      coronary heart disease patients with extensive lesion of the coronary bed].
AB  - The goal of the study was to assess the long-term results of endovascular
      treatment using drug-eluting stents in coronary heart disease patients with
      extensive coronary artery lesion. The study covered 478 patients with diffuse
      coronary artery lesion, including 220 patients receiving endovascular treatment
      and 258 having medical treatment (a comparison group). The immediate angiographic
      results and long-term clinical efficiency of endovascular treatment using
      rapamycin-eluting stents were studied. The follow-up was 2 years. Repeat follow
      ups were undertaken1and 2 years later. The immediate angiographic success rate of
      endovascular treatment for diffuse coronary artery lesions was 89.5%. The two
      year follow-up showed the efficiency and expediency of endovascular treatment for
      extensive coronary artery lesions: the symptoms of angina pectoris occurred
      significantly less frequently symptoms, the exercise endurance was higher, and
      the need for antianginal medications was less in the invasively treated patients.

PMID- 22420205
TI  - [Tissue Doppler imaging during dipyridamole and dobutamine stress
      echocardiography in the diagnosis of coronary heart disease].
AB  - The aim of the study was to determine the sensitivity and specificity of combined
      high-dose dipyridamole and dobutamine stress echocardiography (stress EchoCG) in
      the diagnosis of coronary artery stenotic lesions in coronary heart disease in a
      group of patients who were unable to perform physical exercise, by using
      different assessment criteria (local contractile impairments and systolic
      velocity changes during tissue Doppler imaging). The study enrolled 68 men who
      had undergone dipyridamole and dobutamine stress EchoCG, longitudinal tissue
      Doppler imaging, and coronary angiography. Stress EchoCG could bring up to
      diagnostic criteria in all the patients. Coronary angiography revealed no
      coronary artery lesion in 18 patients, but showed single and multiple vascular
      lesions in 31 and 19 patients, respectively. The sensitivity and specificity of
      combined stress EchoCG were significantly higher than those of stress EchoCG
      examination. The results of combined stress EchoCG allow one to judge to a
      greater validity (96% sensitivity and 100% specificity) local contractile
      impairments corresponding to the blood supply area in the atherosclerosis
      afflicted coronary artery. Analysis of systolic velocity parameters during tissue
      Doppler imaging permits the diagnostic value of the technique to be
      insignificantly improved particularly when the test results are controversial.

PMID- 22420206
TI  - [Analysis of the timing parameters of blood flow in the carotid basin arteries of
      hypertensive patients].
AB  - Vascular duplex ultrasound study with simultaneous ECG recording was performed to
      estimate the timing parameters of blood flow in the common carotid, internal
      carotid, and middle cerebral arteries in patients with grades 1 and 2 arterial
      hypertension. There was an increase in the blood flow acceleration phase index in
      the common carotid and middle cerebral arteries and a reduction in the systolic
      phase index in the internal carotid arteries. There were correlations of phasic
      blood flow parameters in the extra- and intracranial arteries with age and
      lipidogram readings.

PMID- 22420207
TI  - [Ultrasound study in colonic diverticular microperforation].
AB  - This paper deals with the results of ultrasound (US) study in 34 patients with a
      history of colonic diverticulosis, who have been admitted to hospital for the
      clinical manifestations of diverticular microperforation. Diverticulosis was
      verified by X-ray irrigoscopy in 15 patients, by oral contrast-enhanced computed
      tomography in 6, and by colonoscopy in 18. Analysis of US findings revealed the
      major US syndromes of colonic diverticular microperforation, namely a change in
      the intestinal wall as its thickening and lower echogenicity, as well as
      perifocal infiltration and local accumulation of free fluid outside the altered
      bowel.

PMID- 22420208
TI  - [Prognostic value of rectal cancer regression after preoperative chemoradiation
      therapy].
AB  - Despite the international experience enriched in the number of observations of
      combination treatment in patients with rectal cancer, many issues remain to be
      the subject-matter of the discussion. This also applies to the estimation of the
      value of tumor regression after neoadjuvant chemoradiation therapy in order to
      develop indications for sphincter-sparing operations depending on the site of a
      tumor in the organ and their impact on long-term treatment results. The authors
      have gained experience with combination treatment in 157 patients with rectal
      cancer (T2-4 N0-2 M0) receiving neoadjuvant chemoradiation therapy in a
      cumulative radiation dose of 39.5-47 Gy and radical surgery 4-6 weeks after
      radiation. The direct effect of chemoradiation therapy has been investigated
      using a set of studies involving ultrasonography, magnetic resonance imaging,
      endoscopic diagnosis, as well as the data of a postoperative morphological study
      of primary tumor and lymph nodes. The authors have evaluated the impact of
      preoperative chemoradiation therapy on the rate and degree of resorption of a
      primary tumor, including the depth of its invasion through the intestinal wall
      and exit into the cellular tissue, its localization in the organ and the distance
      to the anus, a difference in the preoperative estimation of stages and according
      to the data of pathomorphological studies of intraoperative specimens, etc. The
      degree of tumor resorption was comparatively analyzed with the long-term results
      and the rate of sphincter-sparing operations.

PMID- 22420209
TI  - [Pathobiomechanical impairments of the vertebral column in intervertebral disk
      protrusion and herniation].
AB  - Magnetic resonance imaging of patients with intervertebral disk herniation was
      used to study the stages of degenerative and dystrophic processes in the spinal
      structures in the presence of intervertebral disk protrusion and herniation.
      Differences were found in the pathobiomechanical mechanisms in the spinal motor
      segments of herniation and protrusion in the area of their localization and in
      the adjacent spinal motor segments. Among the symptoms traditionally analyzed,
      joint facet joint arthritis and arthrosoarthritis classified as spondyloarthritis
      by radiodiagnosis were examined for their impact on the rate of herniation and
      protrusion.

PMID- 22420210
TI  - [Role of magnetic resonance imaging in identifying undiagnosed knee fractures].
AB  - The purpose of this investigation was to comparatively analyze the results of
      traditional X-ray study and magnetic resonance imaging (MRI) in traumatic knee
      injuries. The comparative analysis could reveal diagnostic errors in more than
      54% of cases. The early use of MRI to diagnose intraarticular fractures of the
      distal femur, proximal tibia, and patella favors the right choice of a surgical
      treatment policy.

PMID- 22420211
TI  - [The material and technical base of fluorographic units of primary health care
      facilities and its development promises].
AB  - The goal of the study was to assess the status of equipment and the staff
      potential in the fluorography and X-ray units of primary health care facilities
      and to define priorities and the volume of investments for their modernization.
      Two hundred and seventy-two health care facilities were studied through the use
      of questionnaires. The data were processed using standard statistical methods,
      such as calculation of the mean, median, and 95% confidence intervals. Prognosis
      was made for the idling period of equipment during stagnation of measures to
      improve the material and technical base of fluorography units. Priorities for
      modernizing the material and technical base and the staff potential were defined
      for the fluorography units of primary health care facilities. The volume of
      investments required for the modernization was estimated.

PMID- 22420212
TI  - [Radiation studies in blast mine injuries to the torso and limbs].

PMID- 22420213
TI  - [The state-of-the-art of radiodiagnosis of pelvic injuries].

PMID- 22420214
TI  - Inhibitors of tyrosine kinases and phosphatases as a tool for the investigation
      of microtubule role in plant cold response.
AB  - Tyrosine phosphorylation plays a vital role in the variety of signal transduction
      pathways in eukaryotic cells, however its role and relevance in plants are still
      largely unknown. To investigate the functional role of tubulin tyrosine
      phosphorylation in plant cells the interplay between the effects of tyrosine
      kinases (herbimycin A) as well as tyrosine phosphatases (sodium orthovanadate)
      inhibitors on microtubules sensitivity to cold in A. thaliana root cells were
      studied. Since it was found that inhibition of tyrosine kinases significantly
      increased the microtubules sensitivity to cold, while inhibition of tyrosine
      phophatases enhanced their cold-resistance, we suggest an existence of certain
      functional interaction between the phosphorylation on tyrosine residues and
      sensitivity of cortical microtubules to low temperatures.

PMID- 22420215
TI  - [Genetics determination of wheat resistance to Puccinia graminis F. sp. tritici
      deriving from Aegilops cylindrica, Triticum erebuni and amphidiploid 4].
AB  - The lines of winter soft wheat developed in the Plant Breeding and Genetics
      Institute contain new effective introgressive Sr-genes. Line 85/06 possess SrAc1
      gene, lines 47/06, 54/06, 82/06, 85/06, 87/06, 238/06, and 367/06 possess SrAc1
      and SrAc2 derived from Aegilops cylindrica, line 352/06 - SrTe1 and SrTe2 from
      Triticum erebuni, line 12/86-04 - SrAd1 and SrAd2 from Amphidiploid 4 (Triticum
      dicoccoides x Triticum tauschii).

PMID- 22420216
TI  - [Obtaining of hairy-root, callus and suspension carrot culture (Daucus carota L.)
      able to accumulate human interferon alpha-2b].
AB  - Here we report the obtaining of suspension, callus and hairy root culture
      initiated from carrot plants of Nantskaya and Perfektzya variety with the highest
      level of recombinant human interferon alpha-2b accumulation exhibited the highest
      level of plant protein extract antiviral activity (up to 12.8 x 10(3) IU/mg TSP).
      The antiviral activity of callus extracts was significantly lower comparing to
      the activity of plant extracts from parent organisms. However, the antiviral
      activity level of suspension culture extracts (up to 4.42 x 10(3) IU/mg TSP) and
      Ri-root ones (up to 4.42 x 10(3) IU/mg TSP) appeared to be comparable to
      analogical data of antiviral activity of transgenic carrot leaf extracts, this
      way the described cultures could be possibly used for comparatively speedy
      obtaining of recombinant therapeutic protein for curing and preventing of virus
      diseases.

PMID- 22420217
TI  - [Polymorphism of microsatellite loci of European chickpea cultivars].
AB  - Polymorphism of 13 microsatellite loci in 61 chickpea varieties was studied. The
      47 alleles were detected. Three loci were monomorphic, the other ones showed
      polymorphism. Genetic diversity of chickpea varieties in all loci was 0,41
      according to Nei polymorphism index (D). It was concluded that chickpea varieties
      from Europe had insignificant microsatellite loci diversity. The most polymorphic
      group was chickpea varieties from Russia (D = 0,38), the least polymorphic -
      Spanish varieties (D = 0,25). Consensus tree representing the most credible
      divergence of Europe chickpea varieties was constructed. The possible causes of
      clustering chickpea varieties in a common cluster are discussed.

PMID- 22420218
TI  - [Hybridization of crucian carp, Carassius carassius (Linnaeus, 1758), in
      Ukrainian reservoirs and genetic structure of hybrids].
AB  - Hybridization of crucian carps Carassius carassius in polyspecific crucian
      populations of reservoirs of Ukraine and genetic structure of the hybrids were
      investigated using biochemical gene marking and cytometric procedure. The fact of
      wide hybridization between C. auratus and C. carassius was proved to be true by
      large number of hybrids which can form populations consisting only from hybrid
      individuals. Hybrids C. auratus x C. carassius were diploid, tryploid and in
      exceptional cases tetraploid; females and males which most likely breed by
      hybridogenesis. Besides, some clonal hybrids C. carassius x C. gibelio-1
      appearing as tetraploid females, and one triploid female C. carassius x Tinca
      tinca were revealed. It is supported that hybridization of alien C. auratus with
      endemic C. carassius became one of mechanisms of replacement and depressions of
      populations of the last.

PMID- 22420219
TI  - [Phenotypical properties and ability to multilineage differentiation of adipose
      tissue stromal cells during subculturing].
AB  - Morphological and immunophenotypical properties of human adult adipose tissue
      stromal cells (ATSC) at cultivation passage 0 and 4 as well as their ability to
      induced in vitro differentiation into adipogenic and osteogenic directions were
      studied in this work. It was shown that primary cultures of ATSC were
      characterized by the presence of the lower number of cells expressing mesenchymal
      markers (CD73, CD105) than the cells of the 4th passage, but contained
      endothelial progenitor cells expressing CD34 and capable to form capillary-like
      structures within extracellular matrix. Both cell populations could equally
      differentiate into adipogenic and osteogenic lineages.

PMID- 22420220
TI  - [Preservation of parenchymal and stromal progenitors in cryopreserved human fetal
      liver].
AB  - In this paper we show presents of viable population of hepatoblasts, endodermal
      blasts, endothelial and mesenchymal cells in the cryopreserved suspension cells
      of human fetal liver. Also we observed epithelial-mesenchymal transition of
      hepatoblasts in culture. We show that it's possible to apply the method of
      cryopreservation of hematopoietic cells of human fetal liver of the first
      gestation trimester for cryopreservation of parenchymal and stromal cells of
      fetal liver.

PMID- 22420221
TI  - [Clinical genealogical and molecular genetic study of patients with mental
      retardation].
AB  - The results of clinical, genealogical, cytogenetic and molecular genetic studies
      of 113 patients from 96 families with different forms of mental retardation from
      Ukraine are presented. This study was held as part of the CHERISH project of the
      7-th Framework Program. The aim of the project is to improve diagnostics of
      mental retardation in children in Eastern Europe and Central Asia through
      detailed analysis of known chromosomal and gene's aberrations and to find the new
      gene-candidates that cause mental retardation. All patients have normal
      chromosome number (46XY or 46XX). The cases with fragile-X syndrome were
      eliminated using molecular genetic methods. Genome rearrangements were found
      among 28 patients using cytogenetic analysis, multiplex ligation-dependent probe
      amplification (MLPA analysis) ofsubtelomeric regions and array-based comparative
      genomic hybridisation (array CGH screening). In 10 cases known pathogenic CNV's
      were identified, 11 cases are unknown aberrations; their pathogenicity is being
      determined. The rest cases are known nonpathogenic gene rearrangements. Obtained
      results show the strong genetic heterogeneity of hereditary forms of mental
      retardation. The further studies will allow to identificate genes candidates and
      certain mutations in these genes that may be associated with this pathology.

PMID- 22420222
TI  - [Human nerve stem cells in vitro].
AB  - The expansion of Nest-positive nerve stem cells fraction in the culture of human
      fetal brain was investigated in this work. Our results demonstrated the valuable
      increase of the percentage of Nest-positive cells from 44.1 to 62.5% of cell
      population at the response to the presence of EGF and bFGF and using the heat
      inactivated serum in the culture medium. Further differentiation in culture
      tended to decrease of Nest-positive cell amount. Stimulation of the
      neuroinduction with retinoic acid resulted in decrease of the percentage of these
      cells in the population to 14.1%. This data allowed obtaining the nerve cell
      population more effective for using as a graft material in cell therapy.

PMID- 22420223
TI  - DNA methylation in Drosophila melanogaster may depend on lineage heterogeneity.
AB  - DNA methylation has been discovered in Drosophila only recently. Current evidence
      indicates that de novo methylation patterns in drosophila are maintained in a
      different way compared to vertebrates and plants. As the genomic role and
      determinants of DNA methylation are poorly understood in invertebrates, its link
      with several factors has been suggested. In this study, we tested for the
      putative link between DNA methylation patterns in Drosophila melanogaster and
      radiation or the activity of P transposon. Neither of the links was apparent from
      the results, however, we obtained some hints on a possible link between DNA
      methylation pattern and genomic heterogeneity of fly lineages.

PMID- 22420224
TI  - The future of the profession.

PMID- 22420225
TI  - MLS student active learning within a "cloud" technology program.
AB  - In November 2009, the MLS program in a large public university serving a
      geographically large, sparsely populated state instituted an initiative for the
      integration of technology enhanced teaching and learning within the curriculum.
      This paper is intended to provide an introduction to the system requirements and
      sample instructional exercises used to create an active learning technology-based
      classroom. Discussion includes the following: 1.) define active learning and the
      essential components, 2.) summarize teaching methods, technology and exercises
      utilized within a "cloud" technology program, 3.) describe a "cloud" enhanced
      classroom and programming 4.) identify active learning tools and exercises that
      can be implemented into laboratory science programs, and 5.) describe the
      evaluation and assessment of curriculum changes and student outcomes. The
      integration of technology in the MLS program is a continual process and is
      intended to provide student-driven active learning experiences.

PMID- 22420226
TI  - Capturing professionalism in pre-service education: professionalism tool
      development and implementation.
AB  - Recognizing that all health professions educational programs seek to graduate
      students possessing characteristics embodying the nebulous concept of
      professionalism, educators in four imaging and radiation science programs and a
      clinical laboratory science program collaborated to create a measurement tool for
      professionalism in pre-service education. The Student Professional Behavior
      Evaluation Tool and the process for its development and implementation are
      described.

PMID- 22420227
TI  - The utility of essential functions in clinical laboratory science programs.
AB  - OBJECTIVE: Essential functions (EF) define the nonacademic criteria used to
      determine an individual's qualifications for admission and capabilities of
      performing in the classroom and laboratory with or without reasonable
      accommodations. Directors of NAACLS approved and accredited programs were
      surveyed to investigate their knowledge and perceptions of EF and associations
      with disabilities and student behaviors. DESIGN: This was a non-experimental
      survey consisting of questions related to the use of essential functions (EF) and
      student behaviors in NAACLS laboratory programs. SurveyMonkey was used to
      electronically provide the survey of 33 questions to 564 NAACLS programs.
      RESULTS: Descriptive statistics were reported as aggregate data with a response
      rate of 267 (47.3%). EF are utilized in 95.5% of the programs; however, only
      38.6% of the participants responded that EF are required by both the ADA and
      NAACLS. A student had never been dismissed based on EF in 80.0% of the programs.
      Many programs have been successful in mentoring students with disabilities to
      successful completion. Hearing impairment was the most reported disability
      (30.0%). Participants felt most comfortable referring students for academic
      coaching (96.2%) when compared to medical concerns (86.5%), and psychological
      concerns (82.7%). CONCLUSIONS: While most programs utilized EF, many program
      directors were not aware that EF are required by both NAACLS and the ADA.
      Programs have successfully instructed and graduated students with a variety of
      disabilities and generally feel comfortable in referring students for assistance.
      Concerns with inappropriate behaviors present unique, generational challenges to
      faculty.

PMID- 22420228
TI  - Student molecular laboratory performance outcomes in a baccalaureate CLS program.
AB  - As new molecular assays are developed in research laboratories and approved by
      the Food and Drug Administration (FDA) for clinical use, molecular diagnostics
      becomes an integral discipline of clinical laboratory science. Since 2001,
      guidelines of the National Accreditation Agency for Clinical Laboratory Science
      (NAACLS) have required that CLS Educational Programs incorporate molecular
      diagnostics into the curriculum. SETTING: In fall of 2005, CLS
      faculty/researchers, affiliated with a baccalaureate program in an academic
      medical university, incorporated molecular diagnostic lecture content with online
      virtual laboratories into the Clinical Chemistry course. Then beginning in fall
      of 2006, manual performance of molecular laboratory exercises was introduced.
      OBJECTIVE: The aim of this study was to assess whether inclusion of hands-on
      molecular laboratories improved student outcomes on molecular questions during
      the final course examination. METHOD: CLS faculty evaluated student learning by
      written examination of lecture and laboratory content. Researchers performed two
      sample t-tests to establish if significant differences existed in molecular
      questions scores achieved by students exposed to virtual and hands-on exercises.
      RESULTS: The researchers found a statistically significant difference in
      examination performance between the students that had a hands-on experience and
      students with virtual laboratory experience only. Further data analysis suggested
      that hands-on experiential laboratories had the greatest effect on students who
      performed in the middle percentiles. CONCLUSION: The researchers proposed that in
      order to improve examination scores of the weakly performing students other
      interventions may be necessary such as more lecture or laboratory time. This
      prompted development of a full time clinical molecular methods course, separate
      from Clinical Chemistry.

PMID- 22420229
TI  - Grounded theory in medical laboratory science expert practice development.
AB  - Grounded theory and methods related to expert practice development in medical
      laboratory science were described using data from a large national survey of
      medical laboratory scientists (MLS) overlaid on findings from analysis of expert
      practice domains reported in nursing literature. An extensive focus group/expert
      review iterative process followed by a survey of MLS practitioners produced 25
      critical thinking (CT) behaviors important in expert practice. Factor analysis
      was applied to discern common threads or themes linking the CT behaviors. The 25
      important CT behaviors were reduced to a 7-factor structure representing
      constructs underlying the individual, observable CT behaviors. This 7-factor
      structure in MLS was compared to the 7 practice domains identified in expert
      nursing practice. The comparison yielded commonality between MLS and nursing in
      CT behaviors observed in the 7 expert practice domains of both professions:
      professional techniques, caring communication, growing professionally, setting
      priorities, practicing with judgment, anticipating/revising, and creating unique
      meaning. Emergent grounded theory is that (1) critical thinking is a metaprocess
      that facilitates learning by interlinking the more basic processes associated
      with different learning orientations: cognitivist, behaviorist, humanist
      (affective), and situated/contextual learning, (2) CT behaviors are observable
      events following from the CT metaprocess, and (3) observations of CT behaviors
      increase as practice advances from novice to expert. Identification and
      definition of CT behaviors, i.e., practice competencies, along the continuum of
      novice to expert can serve as the foundation for MLS curriculum and instructional
      design as well as measurement and evaluation in both formal and continuing
      education settings.

PMID- 22420230
TI  - Introduction. Building research through MLS curricula.

PMID- 22420231
TI  - Evidence based practice and advanced competencies in a MHS-CLS program.
AB  - The goals, curriculum, implementation, and immediate impacts of an entry-level
      Master of Health Science in Clinical Laboratory Science (MHS-CLS) degree are
      described as compared to the baccalaureate program (BS-CLS) in the same
      institution. The MHS-CLS program was instituted in fall semester, 2008; the
      inaugural class graduated in spring semester 2010. To document the need for the
      MHS-CLS, program statistics, such as the number of students entering the current
      BS-CLS program with previous baccalaureate degrees, numbers of students
      graduating with biology and chemistry degrees in the United States, CLS workforce
      shortages and pending retirement statistics were used. The shortage of CLS
      practitioners able to perform and publish evidence-based practice research also
      supported program need. The MHS-CLS curriculum includes advanced courses,
      advanced competencies incorporated into existing BS-CLS courses, and a capstone
      research project in evidence based practice.

PMID- 22420232
TI  - Research in the Medical Laboratory Science curriculum.
AB  - Medical Laboratory Science (MLS) is increasing its numbers of advanced degree
      offerings and is accelerating involvement in evidence-based practice.
      Expectations of MLS faculty have increased to include research and scholarship.
      Many MLS programs have undergraduate requirements for research. To assist MLS
      faculty as they increase research productivity, information is provided to guide
      professionals and students striving to expand their research achievements.

PMID- 22420233
TI  - Multiple comparison analysis testing in ANOVA.
AB  - The Analysis of Variance (ANOVA) test has long been an important tool for
      researchers conducting studies on multiple experimental groups and one or more
      control groups. However, ANOVA cannot provide detailed information on differences
      among the various study groups, or on complex combinations of study groups. To
      fully understand group differences in an ANOVA, researchers must conduct tests of
      the differences between particular pairs of experimental and control groups.
      Tests conducted on subsets of data tested previously in another analysis are
      called post hoc tests. A class of post hoc tests that provide this type of
      detailed information for ANOVA results are called "multiple comparison analysis"
      tests. The most commonly used multiple comparison analysis statistics include the
      following tests: Tukey, Newman-Keuls, Scheffee, Bonferroni and Dunnett. These
      statistical tools each have specific uses, advantages and disadvantages. Some are
      best used for testing theory while others are useful in generating new theory.
      Selection of the appropriate post hoc test will provide researchers with the most
      detailed information while limiting Type 1 errors due to alpha inflation.

PMID- 22420234
TI  - Is there an association of allergy and cardiovascular disease?
AB  - Cardiovascular diseases and allergic diseases occur commonly in developed
      countries. They lead to serious health complications and significantly impair the
      quality of life. Both types of diseases are characterized by excessive
      inflammatory processes. Recent studies suggest a link between allergy and an
      increased risk of cardiovascular disease, resulting from overactivity of the
      immune system in allergic diseases and increased synthesis of proinflammatory
      mediators, which has been well documented in the pathogenesis of atherosclerosis.
      The aim of this article is to present current data on the role of proinflammatory
      factors in the pathogenesis of cardiovascular diseases and allergies and on
      potential relationship between these disorders.

PMID- 22420235
TI  - Anti-Mullerian hormone: a unique biochemical marker of gonadal development and
      fertility in humans.
AB  - Anti-Mullerian hormone (AMH) is a glycoprotein belonging to the transforming
      growth factors (TGF-P). AMH plays a fundamental role in the regression of
      Mullerian ducts in male embryo. In its absence, Mullerian ducts develop into
      female inner reproductive organs. In boys, it is significantly produced in
      Sertoli cells of testes until puberty and then slowly decreases to residual
      values for the rest of the men's life. AMH serves as a biochemical marker of the
      presence of testes in cryptorchidic males. In females, AMH is secreted by
      granulosa cells of small follicles in the ovary. Serum values are almost
      undetectable during infancy and then rapidly increase with the onset of puberty,
      reflecting the initial recruitment of primordial follicles. AMH is produced in
      growing follicles until they reach a stage when dominant follicle is detached
      from a cohort of antral follicles. The measurement of serum AMH levels during
      woman's reproductive life represents an ideal tool for the assessment of the
      ovarian follicular reserve. The advantage of AMH in relation to the ovarian
      steroid hormones is that serum levels do not fluctuate significantly during the
      menstrual cycle. In addition, circulating AMH strongly correlates with antral
      follicle count (AFC), visualized by ultrasound in the follicular phase of the
      cycle. As the number and quality of the oocytes diminish throughout the woman's
      reproductive life, serum concentrations of AMH gradually decrease and fall below
      detectable levels in menopause. This could be of particular interest in
      subfertile and infertile women undergoing assisted reproductive techniques (ART)
      in achieving pregnancy.

PMID- 22420236
TI  - Endothelins -- clinical perspectives.
AB  - Endothelins (ET) are a group of endogenous peptides, which have a strong and long
      lasting vasoconstrictive effect. Three isoforms of endothelins coded by three
      different genes have been identified to date. Endothelin-1 (ET-1) is the most
      potent vasoconstrictive agent currently identified, and it was originally
      isolated and characterized from the culture media of aortic endothelial cells.
      Two other isoforms, named endothelin-2 (ET-2) and endothelin-3 (ET-3), were
      subsequently identified, along with structural homologues isolated from the venom
      ofActractapis engaddensis known as the sarafotoxins. The biological effects of
      endothelin production are determined via activation of one or two G-protein
      coupled receptors, endothelin receptors A (ETRA) and B (ETRB1 and ETRB2).
      Recently endothelin receptor C (ETRC) was discovered, however, its functions and
      distribution still remain unclear. The effects mediated by ET-1 via ETRA are
      vasoconstriction, bronchoconstriction and secretion of aldosterone. Agonists
      related to the ETRB1 activation cause vasodilatation by stimulating NO, PGI2 and
      endothelium-derived hyperpolarizing factor (EDHF). In contrast, coupling to ETRB2
      causes vasoconstriction. Involvement of ET has been demonstrated in the
      pathophysiology of certain disorders. In this review, we discuss the
      physiological and pathophysiological role of endothelium-derived ET-1, the
      pharmacology of its two receptors, focusing on the role of ET-1 in the
      development of some pathophysiological conditions.

PMID- 22420237
TI  - New insights in the pathophysiology of inflammation.

PMID- 22420238
TI  - Faecal calprotectin in the diagnosis of inflammatory bowel disease.
AB  - Suspicion of inflammatory bowel disease should be raised in any patient with
      chronic or recurrent abdominal pain and diarrhoea. However, symptoms of
      inflammatory bowel disease (IBD) overlap with functional gastrointestinal
      disorders and those patients may not need endoscopy. Currently, colonoscopy with
      multiple biopsies is considered the gold standard to establish the diagnosis of
      IBD. Unfortunately, patient selection for endoscopy based on symptoms is not
      reliable. The use of guidelines of appropriateness for endoscopy yields
      significantly more significant findings but the selection criteria suffer from
      low specificity. Calprotectin is a calcium binding protein of neutrophil
      granulocytes that correlates well with neutrophil infiltration of the intestinal
      mucosa when measured in faeces. In the last decade, a large body of evidence on
      the diagnostic value of faecal calprotectin has accumulated and measurement of
      calprotectin in faeces has been suggested as a surrogate marker of intestinal
      inflammation. Testing of faecal calprotectin has been highly useful to
      distinguish organic from functional intestinal disorders in patients with
      abdominal complaints. Additionally, faecal calprotectin has reliably identified
      colonic inflammation in patients with suspected IBD. The use of this inexpensive
      and widely available test in the evaluation and risk stratification in patients
      with abdominal complaints is likely to increase in the future.

PMID- 22420239
TI  - Biomarkers of inflammation and cardiac remodeling: the quest of relevant
      companions for the risk stratification of heart failure patients is still
      ongoing.
AB  - Heart failure (HF) is a frequent chronic disease in elderly people and represents
      a major health and economic burden. The accurate diagnosis of HF and the
      identification of high risk patients is mandatory to select the appropriate
      therapy and care. HF is associated to cardiac remodeling and inflammation and to
      the release of neurohormones. If natriuretic peptides remain the biomarkers of
      choice for the diagnosis and the prognosis of HF, several biomarkers related to
      cardiac remodeling and inflammation are available for testing and may add
      valuable information for the risk estimation of HF patients and for the selection
      of the most appropriated therapy. Furthermore, the quest for new efficient
      biomarkers of cardiac remodeling and inflammation is still ongoing and new
      candidates have been identified for a potential use in daily clinical practices.
      However, before their potential translation to routine parameters several
      challenges ranging form the analytical validation to the cost-effectiveness
      estimation should be considered.

PMID- 22420240
TI  - Molecular pathways in cancer-related inflammation.
AB  - Accumulating evidence shows that chronic inflammation is associated to increased
      risk of cancer. An inflammatory component is present also in the microenvironment
      of tumours epidemiologically unrelated to inflammation. Extensive investigations
      over the past decade have uncovered many of the important mechanistic pathways
      underlying cancer-related inflammation. Pathways linking inflammation and cancer
      have been identified: an intrinsic one (driven by genetic events that cause
      neoplasia) and an extrinsic one (driven by inflammatory conditions which
      predispose to cancer). Smouldering inflammation is a component of the tumour
      microenvironment and is a recognized hallmark of cancer. Key orchestrators at the
      intersection of the intrinsic and extrinsic pathways include transcription
      factors (e.g. Nuclear Factor kappa-B, NFKB) that modulate the inflammatory
      response through soluble mediators (cytokines, chemokines) and cellular
      components (e.g. tumor-associated macrophages), promoting tumorigenesis. NFKB
      aids in the proliferation and survival of malignant cells, promotes angiogenesis
      and metastasis, subverts adaptive immunity, and alters responses to hormones and
      chemotherapeutic agents. Emerging evidence also suggests that persistent
      inflammation promotes genetic instability. Thus, cancer-related inflammation
      represents a target for innovative diagnostic and therapeutic strategies.

PMID- 22420241
TI  - Neonatal sepsis.
AB  - Neonatal sepsis is the most common cause of neonatal deaths with high mortality
      despite treatment. Neonatal sepsis can be classified into two subtypes depending
      upon onset of symptoms. There are many factors that make neonates more
      susceptable to infection. Signs of sepsis in neonates are often non-specific and
      high degree of suspicion is needed for early diagnosis. Some laboratory
      parameters can be helpful for screening of neonates with neonatal sepsis, but
      none of it is specific and sensitive enough to be used singly. Diagnostic
      approach mostly focuses on history and review of non specific signs and symptoms.
      Antibiotic treatment is the mainstay of treatment and supportive care is equally
      important. The aim of this review is to give an overview of neonatal sepsis,
      including incidence, etiology, clinical picture, diagnostics and therapy.

PMID- 22420242
TI  - Neutrophil CD64 as a sepsis biomarker.
AB  - Neutrophilic granulocytes express their Fcgamma receptor, also known as the CD64
      antigen, predominantly when they are activated. This makes neutrophil CD64 a
      potential biomarker for infection and sepsis. Indeed there is ample literature on
      the diagnostic utility of neutrophil CD64 in a variety of diseases. This review
      summarizes the literature on its application as a sepsis biomarker, in adults as
      well as in neonates and infants. The available data indicate that neutrophil CD64
      seems to have high sensitivity (86%) and specificity (87%), but the
      methodological quality of most studies is questionable. Nevertheless, neutrophil
      CD64 appears to be a better diagnostic test than traditional hematological
      assays, C-reactive protein and probably even procalcitonin. Application of
      neutrophil CD64 in other conditions than sepsis is briefly presented. Finally,
      future clinical studies are discussed which are needed in order to confirm the
      diagnostic performance of this promising biomarker.

PMID- 22420243
TI  - Increased DAPK1 but decreased CCL2 plasma levels of nucleic acids in patients
      with stable angina.
AB  - INTRODUCTION: We hypothesized that patients with stable angina have increased
      plasma levels of mRNA from genes responsible for atherosclerotic plaque
      development and destabilisation, i.e. from death-associated protein kinase
      (DAPK1) and monocyte chemotactic protein-1 (CCL2). MATERIALS AND METHODS: Nucleic
      acids were isolated from plasma of patients with stabile angina and healthy
      subjects as controls. mRNAs were transcribed to cDNAs, quantified by real-time
      PCR and standardized to the amount of a reference gene. Reagents for PCR
      quantification are declared to be mRNA specific, but in our test conditions DNA
      was found to interfere in both assays. RESULTSs: Patients had 5.1-times higher
      plasma level of DAPK1 nucleic acids (mRNA and DNA) than controls (P < 0.001) and
      the highest levels were associated with the presence of diabetes. However, plasma
      levels of CCL2 tended to be lower than in controls, and in statin-treated
      patients the decrement reached significance (-66.3%; P = 0.041). CONCLUSION: The
      estimated levels are explicable in terms of current knowledge. Further studies
      with specific assays for mRNA PCR quantification are reasonable to access whether
      this approach offers non-invasive in vive assessment and monitoring of gene
      expression profile in atherosclerotic vascular beds.

PMID- 22420244
TI  - Studies on in vitro hemolysis and utility of corrective formulas for reporting
      results on hemolyzed specimens.
AB  - INTRODUCTION: Spuriously hemolyzed specimens are the most common preanalytical
      problems in clinical laboratories. Corrective formulas have been proposed to
      allow the laboratory to release test results on these specimens. This study aimed
      to assess the influence of spurious hemolysis and reliability of corrective
      formulas. MATERIALS AND METHODS: Blood collected into lithium heparin vacuum
      tubes was divided in aliquots and subjected to mechanical injury by aspiration
      with an insulin syringe equipped with a thin needle (30 gauge). Each aliquot
      (numbered from "#0" to "#5") was subjected to a growing number of passages
      through the needle, from 0 to 5 times. After hematological testing, plasma was
      separated by centrifugation and assayed for lactate dehydrogenase (LD), aspartate
      aminotransferase (AST), potassium and hemolysis index (HI). RESULTS: Cell-free
      hemoglobin concentration gradually increased from aliquot #0 (HI: 0) to #5 (HI:
      76 +/- 22, cell-free hemoglobin approximately 37.0 g/L). A highly significant
      inverse correlation was observed between HI and red blood cell count (RBC),
      hematocrit, mean corpuscular volume (MCV), LD, AST, potassium, whereas the
      correlation was negative with mean corpuscular hemoglobin (MCH). No correlation
      was found with hemoglobin, platelet count and glucose. A trend towards decrease
      was also observed for white blood cells count. The ANCOVA comparison of analyte
      specific regression lines from the five subjects studied revealed significant
      differences for all parameters except potassium. In all circumstances the sy,x of
      these equations however exceeded the allowable clinical bias. CONCLUSIONS:
      Mechanical injury of blood, as it might arise from preanalytical problems, occurs
      dishomogeneously, so that corrective formulas are unreliable and likely
      misleading.

PMID- 22420245
TI  - Evaluation of hematocrit bias on blood glucose measurement with six different
      portable glucose meters.
AB  - INTRODUCTION: Measurement and monitoring of blood glucose levels in hospitalized
      patients with portable glucose meters (PGMs) is performed widely and is an
      essential part of diabetes monitoring, despite the increasing evidence of several
      interferences which can negatively bias the accuracy of measurements. The purpose
      of this study was to evaluate the effect of the hematocrit on the analytical
      performances of different PGMs as compared with a reference laboratory assay.
      MATERIALS AND METHODS: The effect of various hematocrit values (approximiately
      0.20, approximiately 0.45 and approximiately 0.63 L/L) were assessed in three
      whole blood specimens with different glucose concentration (approximiately 1.1,
      approximiately 13.3, and approximiately 25 mmol/L) by using six different
      commercial PGMs. The identical samples were also tested with the laboratory
      reference assay (i.e., hexokinase). The percentage difference from the laboratory
      assay (%Diff) was calculated as follows: % Diff = average PGM value - value from
      laboratory assay x 100 / value from laboratory assay. RESULTS: The %Diff of the
      six different PGMs were rather broad, and comprised between 56.5% and -34.8% in
      the sample with low glucose concentration (approximiately 1.1 mmol/L), between
      40% and -32% in the sample with high glucose concentration (approximiately 13.3
      mmol/L), and between -50% and 15% in the sample with very high glucose
      concentration (approximiately 25 mmol/L), respectively. It is also noteworthy
      that a very high hematocrit value (up to 0.63 L/L) generated a remarkable
      negative bias in blood glucose (-35%) as measured with the laboratory assay, when
      compared with the reference sample (hematocrit 0.45 L/L). CONCLUSION: The results
      of this analytical evaluation clearly confirm that hematocrit produces a strong
      and almost unpredictable bias on PGMs performances, which is mainly dependent on
      the different type of devices. As such, the healthcare staff and the patients
      must be aware of this limitation, especially in the presence of extreme
      hematocrit levels, when plasma glucose assessment with the reference laboratory
      technique might be advisable.

PMID- 22420246
TI  - Serum calcium, magnesium, phosphorous and lipid profile in healthy Iranian
      premenopausal women.
AB  - INTRODUCTION: Recent epidemiological evidence suggests that alteration in
      calcium, phosphorous or magnesium metabolism may have direct cardiovascular
      consequences. However, it is unknown whether variations in serum values of these
      minerals are in relationship with lipid profile and adiposity as metabolic risk
      factors of cardiovascular events in premenopausal women independent of
      confounders. The aim of this study was to investigate the relationship between
      serum calcium, magnesium and phosphorous with lipid profile in healthy
      premenopausal women. MATERIALS AND METHODS: This study was performed on 82
      reproductive age women aged 17-50 who were randomly selected from general
      population of Tabriz, Iran. They were assigned into obese and none-obese groups.
      Weight and height for BMI calculation were measured using a calibrated Seca scale
      and cotton ruler which was attached to the wall. Body composition was analyzed by
      bioelectrical impedance analysis (BIA). Serum magnesium, calcium and phosphorous
      were measured colorimetrically; fasting blood glucose (FBG) and serum lipids were
      assessed by enzymatic methods. RESULTS: Obese woman had significantly lower serum
      magnesium (P = 0.035) and significantly higher fasting blood glucose (P = 0.028),
      total cholesterol (P = 0.035), triglyceride (P = 0.019), low density lipoprotein
      (P =0.003) and parathyroid hormone concentrations (P = 0.031) compared to non
      obese women. In correlation coefficient analysis, serum calcium concentrations
      had a positive weak relationship with total cholesterol (r = 0.267, P = 0.013)
      and triglyceride (r = 0.301, P = 0.005) concentrations in all participants;
      whereas in separate analysis of subjects as obese and non obese groups, these
      relationships lost their significance. Serum phosphorous had a weak positive
      relationship with total cholesterol (r = 0.31, P = 0.002) and an inverse weak
      relationship with parathyroid hormone (r = -0.32, P = 0.002). After adjusting for
      confounding variables by multiple regression analysis, the positive relationship
      between serum calcium, triglyceride, high density lipoprotein and low density
      lipoprotein cholesterol were significant. CONCLUSION: Our results indicate that
      abnormality in serum calcium and phosphorous is significantly correlated with
      serum lipids. Further studies are warranted for interpretation of these
      associations and understanding the underlying mechanisms.

PMID- 22420247
TI  - Hemoglobin Hasharon and hemoglobin NYU in subjects of German origin.
AB  - Determination of HbA1c values with high performance liquid chromatography (HPLC)
      occasionally reveals hemoglobin anomalies with no or minimal clinical evidence.
      We coincidentally detected two cases of Hb Hasharon, an alpha globin gene
      mutation, in two heterozygous patients and one case of Hb NYU, a delta globin
      gene mutation, in another patient. Both anomalies have not been described in
      subjects of German origin to date. Characterization was carried out with HPLC,
      hemoglobin electrophoresis, capillary zone electrophoresis, DNA sequencing,
      complete blood count and clinical chemical analysis.

PMID- 22420248
TI  - Combining tactics to exploit Allee effects for eradication of alien insect
      populations.
AB  - Invasive species increasingly threaten ecosystems, food production, and human
      welfare worldwide. Hundreds of eradication programs have targeted a wide range of
      nonnative insect species to mitigate the economic and ecological impacts of
      biological invasions. Many such programs used multiple tactics to achieve this
      goal, but interactions between tactics have received little formal consideration,
      specifically as they interact with Allee dynamics. If a population can be driven
      below an Allee threshold, extinction becomes more probable because of factors
      such as the failure to find mates, satiate natural enemies, or successfully
      exploit food resources, as well as demographic and environmental stochasticity. A
      key implication of an Allee threshold is that the population can be eradicated
      without the need and expense of killing the last individuals. Some combinations
      of control tactics could interact with Allee dynamics to increase the probability
      of successful eradication. Combinations of tactics can be considered to have
      synergistic (greater efficiency in achieving extinction from the combination),
      additive (no improvement over single tactics alone), or antagonistic (reduced
      efficiency from the combination) effects on Allee dynamics. We highlight examples
      of combinations of tactics likely to act synergistically, additively, or
      antagonistically on pest populations. By exploiting the interacting effects of
      multiple tactics on Allee dynamics, the success and cost-effectiveness of
      eradication programs can be enhanced.

PMID- 22420249
TI  - Duration and frequency of a high temperature pulse affect survival of emergence
      ready Megachile rotundata (Hymenoptera: Megachilidae) during low-temperature
      incubation.
AB  - Synchronizing Megachile rotundata (F.) nesting activity with alfalfa bloom is
      essential for ensuring optimal pollination for alfalfa seed production. This is
      achieved by timing the initiation of spring bee incubation so that adults will
      emerge -2 wk before peak bloom. If weather conditions change so as to delay the
      bloom, bee managers will commonly expose the developing bees to a period of low
      temperature incubation to slow their development. We have previously demonstrated
      survival during low-temperature incubation can be significantly increased by
      using a fluctuating thermal regime (FTR) where the bees receive a daily pulse at
      20 degrees C. A FTR incubation protocol is composed of a number of different
      components, such as the base and pulse temperatures, and the duration and
      frequency of the pulse. In this investigation, the effect of the duration of the
      pulse (5-120 min) and the frequency of a pulse (twice daily to weekly) on the
      survival of developing M. rotundata was examined. A pulse as short as 5 min at 20
      degrees C increased survival of the developing bees as compared with the constant
      6 degrees C controls. Increasing the pulse duration induced a further increase in
      tolerance to 6 degrees C. As with the pulse duration, increasing the pulse
      frequency from once weekly to twice daily had a significant effect on improving
      the bees tolerance to low-temperature incubation. This investigation further
      strengthens the argument that a FTR protocol is superior to using a constant low
      temperature exposure for interrupting the spring incubation of M. rotundata.

PMID- 22420250
TI  - Assessing the mating 'health' of commercial honey bee queens.
AB  - Honey bee queens mate with multiple males, which increases the total genetic
      diversity within colonies and has been shown to confer numerous benefits for
      colony health and productivity. Recent surveys of beekeepers have suggested that
      'poor queens' are a top management concern, thus investigating the reproductive
      quality and mating success of commercially produced honey bee queens is
      warranted. We purchased 80 commercially produced queens from large queen breeders
      in California and measured them for their physical size (fresh weigh and thorax
      width), insemination success (stored sperm counts and sperm viability), and
      mating number (determined by patriline genotyping of worker offspring). We found
      that queens had an average of 4.37 +/- 1.446 million stored sperm in their
      spermathecae with an average viability of 83.7 +/- 13.33%. We also found that the
      tested queens had mated with a high number of drones (average effective paternity
      frequency: 17.0 +/- 8.98). Queen "quality" significantly varied among commercial
      sources for physical characters but not for mating characters. These findings
      suggest that it may be more effective to improve overall queen reproductive
      potential by culling lower-quality queens rather than systematically altering
      current queen production practices.

PMID- 22420251
TI  - Intraspecific competition effects on Aethina tumida (Coleoptera: Nitidulidae).
AB  - Two kinds of experiments were conducted with Aethina tumida Murray larvae over
      four temperatures: "consumption" experiments, in which larvae and diet were
      weighed to determine food consumption rates under conditions of unlimited food
      and few conspecifics; and "competition" experiments, in which varying numbers of
      larvae were presented with the same amount of honey and pollen diet, and larval
      weight at final instar was used to determine competition effects. In consumption
      experiments temperature, diet and their interaction all had significant effects
      on the ratio of larval weight to the weight of food consumed, which was higher at
      24 degrees C than at any other temperature. In competition experiments, three
      relationships were examined and modeled: that between the number of larvae per
      experimental unit and the average weight of those larvae; that between average
      larval and adult weights; and that between average adult weight and survivorship
      to adult (emergence rate). An exponential decay function was fit to the
      relationship between number of larvae per experimental unit and their average
      weight. Average adult weight was linearly correlated with larval weight.
      Likewise, emergence rates for adults < 11.6 mg in weight were linearly correlated
      with adult weights, but no significant relationship was observed for heavier
      adults. Using these relationships, the reproductive potential for A. tumida were
      estimated for a frame of honey and pollen. Information on resource acquisition by
      A. tumida will be useful in evaluating the impact of different factors on beetle
      population dynamics, such as bee hygienic behavior or control strategies used by
      the beekeeper.

PMID- 22420252
TI  - The effect of feeder location on pollen collection by bumble bees in a tomato
      greenhouse in Ontario, Canada.
AB  - The foraging behavior of bumble bees (Bombus impatiens Cresson) was examined as a
      function of feeder location containing sugar solution in a commercial tomato
      greenhouse in Manotick, Ontario, Canada. The feeders were located within the nest
      box (fed-close) or placed 1.5 m away (fed-far) and the placement of the two types
      of colonies was counterbalanced over time. No effect of feeder location was found
      in colony activity levels or in pollen load size. A foraging trade-off between
      sugar solution and pollen collection, however, was found: the proportion of
      foraging trips in which pollen was brought back was significantly reduced for fed
      far colonies, which contrasts with our laboratory study in which the opposite
      effect was found. We interpret our findings as possibly reflecting a limitation
      in pollen supply in the greenhouse: an already possibly strained ability to find
      and bring back pollen to the colony was accentuated by increasing the task
      demands of collecting sugar solution.

PMID- 22420253
TI  - Transmission of Iris yellow spot virus by Frankliniella fusca and Thrips tabaci
      (Thysanoptera: Thripidae).
AB  - Thrips-transmitted Iris yellow spot virus (IYSV) (Family Bunyaviridae, Genus
      Tospovirus) affects onion production in the United States and worldwide. The
      presence of IYSV in Georgia was confirmed in 2003. Two important thrips species
      that transmit tospoviruses, the onion thrips (Thrips tabaci (Lindeman)) and the
      tobacco thrips (Frankliniella fusca (Hinds)) are known to infest onion in
      Georgia. However, T. tabaci is the only confirmed vector of IYSV. Experiments
      were conducted to test the vector status of F. fusca in comparison with T.
      tabaci. F. fusca and T. tabaci larvae and adults reared on IYSV-infected hosts
      were tested with antiserum specific to the nonstructural protein of IYSV through
      an antigen coated plate ELISA. The detection rates for F. fusca larvae and adults
      were 4.5 and 5.1%, respectively, and for T. tabaci larvae and adults they were
      20.0 and 24.0%, respectively, indicating that both F. fusca and T. tabaci can
      transmit IYSV. Further, transmission efficiencies of F. fusca and T. tabaci were
      evaluated by using an indicator host, lisianthus (Eustoma russellianum
      (Salisbury)). Both F. fusca and T. tabaci transmitted IYSV at 18.3 and 76.6%,
      respectively. Results confirmed that F. fusca also can transmit IYSV but at a
      lower efficiency than T. tabaci. To attest if low vector competency of our
      laboratory-reared F. fusca population affected its IYSV transmission capability,
      a Tomato spotted wilt virus (Family Bunyaviridae, Genus Tospovirus) transmission
      experiment was conducted. F. fusca transmitted Tomato spotted wilt virus at a
      competent rate (90%) suggesting that the transmission efficiency of a competent
      thrips vector can widely vary between two closely related viruses.

PMID- 22420254
TI  - Species within the Bemisia tabaci (Hemiptera: Aleyrodidae) complex in soybean and
      bean crops in Argentina.
AB  - The whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is a cryptic
      species complex that contains some of the most damaging pests in tropical and
      subtropical regions. Recent studies suggested that this complex is composed of at
      least 24 distinct species. We use the approach from these studies to consider the
      identity of B. tabaci in Argentina. Previous studies have suggested the presence
      of a B. tabaci presumably indigenous to the Americas and referred to as the BR
      biotype in Argentina. We placed the entity referred to as the BR biotype within
      the B. tabaci cryptic species complex using whiteflies collected in soybean and
      bean crops in northern and central Argentina. The whiteflies were assigned using
      the mitochondrial cytochrome oxidase (mtCOI) gene. Four unknown haplotypes plus
      two Argentina sequences from GenBank formed a cluster that was basal to the rest
      of the New World sequences. These sequences diverged from the consensus sequence
      across the range of 3.6 to 4.3%. Applying the species assignment rules of recent
      studies suggests that the individuals from Argentina form a separate species. A
      fifth unknown haplotype fell within the New World putative species and formed a
      distinct cluster with haplotypes from Panama. These results suggest that
      Argentina has two indigenous species belonging to the B. tabaci cryptic species
      complex. Rather than using mtCOI sequencing for all B. tabaci collected, a simple
      random amplified polymorphic DNA-polymerase chain reaction diagnostic was used
      and tested along with previously published primers designed to work specifically
      with the BR biotype from Brazil. These primers were either unable to distinguish
      between the two indigenous members of the complex in Argentina or indicated a
      difference when none was evident on the basis of mtCOI sequence comparison.

PMID- 22420255
TI  - Irradiation of adult Epiphyas postvittana (Lepidoptera: Tortricidae): egg
      sterility in parental and F1 generations.
AB  - Adult Epiphyas postvittana Walker were irradiated using a Cobalt 60 source to
      determine the dose needed to achieve complete egg sterility of mated female
      moths, and egg sterility of female moths mated to F1 generation males. Adult male
      and female E. postvittana were irradiated at 100, 200, 250, and 300 Gy and their
      fertility (when crossed with normal moths) was compared with nonirradiated moths.
      Viable progeny (determined by egg hatch) were found at doses of 100 and 200 Gy,
      but very little at 250 and 300 Gy. In particular, there was no survival of female
      progeny into the F1 generation. Males irradiated at 250 and 300 Gy had very low
      egg eclosion rates (2.25 and 1.86% at 250 and 300 Gy, respectively) when mated
      with normal females. The F2 generation from those male progeny had a mean percent
      hatched of < 1.02%. Based on our results, a dose of 250-300 Gy is recommended for
      irradiation of E. postvittana adults used for sterile insect technique (SIT) if
      sterility of parental moths is the desired outcome. Our data also suggests that
      inclusion of F1 hybrid sterility rather than parental generation sterility into
      programs using the SIT may allow for doses lower than what we have reported,
      especially during initial phases of an eradication program where increase fitness
      of moths might be desirable. Further research is needed to verify the use of F1
      hybrid sterility in light brown apple moth SIT programs.

PMID- 22420256
TI  - A behavioral method for separation of house fly (Diptera: Muscidae) larvae from
      processed pig manure.
AB  - A behavioral method applicable in biodegradation facilities for separation of
      house fly (Musca domestica L.) larvae from processed pig manure is presented. The
      method is based on placing a cover over the larval rearing tray, while escaping
      larvae are collected in collection trays. Separation units must be placed in a
      dark room to avoid negative phototactic responses of the larvae. After 24 h of
      separation, over 70% of the larvae escaped from processed manure and were
      collected in collection trays. Most of the larvae pupated within 48 h after
      separation. Mean weight of pupae recovered from manure residue was not
      significantly different from mean weight of pupae of separated individuals.
      Eclosion rate of pupae recovered from manure residue was significantly lower than
      eclosion of separated individuals, and was strongly related to separation
      success. Factors responsible for escape behavior of larvae are discussed.

PMID- 22420257
TI  - Imidacloprid in melon guttation fluid: a potential mode of exposure for pest and
      beneficial organisms.
AB  - ELISA techniques were used to detect imidacloprid in guttation fluid of young
      cantaloupe plants in Arizona. Imidacloprid was detected at up to 4.1 microg/ml
      (ppm) in a coincidental guttation collection 3 d after a top label rate soil
      application and at 37 microg/ml one d after a separate top label rate soil
      application study. These imidacloprid titers exceed reported median oral
      toxicities for several insect species by factors of 10 or more. Pesticides in
      guttation fluid are a relatively unexplored route of exposure for both pest and
      beneficial insects, and could represent an important risk for both of these
      groups in guttation-prone environments.

PMID- 22420258
TI  - Plant terpenoids: acute toxicities and effects on flight motor activity and wing
      beat frequency in the blow fly Phaenicia sericata.
AB  - We evaluated the acute toxicities and the physiological effects of plant
      monoterpenoids (eugenol, pulegone, citronellal and alpha-terpineol) and
      neuroactive insecticides (malathion, dieldrin and RH3421) on flight muscle
      impulses (FMI) and wing beat signals (WBS) of the blow fly (Phaenicia sericata).
      Topically-applied eugenol, pulegone, citronellal, and alpha-terpineol produced
      neurotoxic symptoms, but were less toxic than malathion, dieldrin, or RH3421.
      Topical application of eugenol, pulegone, and citronellal reduced spike amplitude
      in one of the two banks of blow fly dorsolongitudinal flight muscles within 6-8
      min, but with citronellal, the amplitude of FMIs reverted to a normal pattern
      within 1 hr. In contrast to pulegone and citronellal, where impulse frequency
      remained relatively constant, eugenol caused a gradual increase, then a decline
      in the frequency of spikes in each muscle bank. Wing beating was blocked
      permanently within 6-7 min of administering pulegone or citronellal and within 16
      mins with eugenol. alpha-Terpineol-treated blow flies could not beat their wings
      despite normal FMI patterns. The actions of these monoterpenoids on blow fly
      flight motor patterns are discussed and compared with those of dieldrin,
      malathion, RH3421, and a variety of other neuroactive substances we have
      previously investigated in this system. Eugenol, pulegone and citronellal readily
      penetrate blow fly cuticle and interfere with flight muscle and/or central
      nervous function. Although there were differences in the effects of these
      compounds, they mainly depressed flight-associated responses, and acted similarly
      to compounds that block sodium channels and facilitate GABA action.

PMID- 22420259
TI  - The joint toxicity of type I, II, and nonester pyrethroid insecticides.
AB  - Evidence suggests that there are separate binding domains for type I and II
      pyrethroid insecticides on the voltage gated sodium channel of the nerve cell
      axon, but there are no studies that have examined the mixture toxicity of
      nonester pyrethroids and type I and II pyrethroids. Therefore, we examined the
      effect of nonester pyrethroid (etofenprox), type I (permethrin), and type II
      (cypermethrin) pyrethroid insecticides alone and in all combinations to
      Drosophila melanogaster Meigen. The combination of permethrin + etofenprox and
      permethrin + cypermethrin demonstrated antagonistic toxicity, while the
      combination of cypermethrin + etofenprox demonstrated synergistic toxicity. The
      mixture ofpermethrin + cypermethrin + etofenprox demonstrated additive toxicity.
      The toxicity of permethrin + cypermethrin was significantly lower than the
      toxicity of cypermethrin alone, but the combination was not significantly
      different from permethrin alone. The toxicity of permethrin + cypermethrin +
      etofenprox was significantly greater than the toxicity of both permethrin and
      etofenprox alone, but it was significantly lower than cypermethrin alone. The
      mixture of permethrin and etofenprox was significantly less toxic than
      permethrin. The explanation for the decreased toxicity observed is most likely
      because of the competitive binding at the voltage-gated sodium channel, which is
      supported by physiological and biochemical studies of pyrethroids. Our results
      demonstrate that the assumption that the mixture toxicity of pyrethroids would be
      additive is not adequate for modeling the mixture toxicity of pyrethroids to
      insects.

PMID- 22420260
TI  - Assessment of toxicity risk of insecticides used in rice ecosystem on
      Trichogramma japonicum, an egg parasitoid of rice lepidopterans.
AB  - Both chemical and biological methods are essential for control of insects, for
      example, lepidopterans, on rice. Thus, it is important to know the effect of
      chemicals on the biological control agents. In this study, we assessed the
      toxicity of commonly used insecticides on a biological control agent,
      Trichogramma japonicum Ahmead (an egg parasitoid of rice lepidopterans) by using
      a dry film residue method. Results showed that thirty insecticides from seven
      chemical classes exhibited various degree of toxicity to this parasitoid. Among
      the seven classes of chemicals tested, organophosphates (chlorpyrifos,
      fenitrothion, phoxim, profenofos, and triazophos) and carbamates (carbaryl,
      carbsulfan, isoprocarb, metolcarb, and promecarb) exhibited the highest intrinsic
      toxicity to T. japponicum, with an LC50 of 0.035 (0.029-0.044) to 0.49 (0.34
      0.87) mg active ingredient (a.i.) L(-1), followed by antibiotics (abamectin,
      emamectin benzoate, and ivermectin), phenylpyrazoles (butane-fipronil, ethiprole,
      and fipronil), pyrethroids (cyhalthrin, cypermethrin, fenpropathrin, and lambda
      cyhaothrin), and neonicotinoids (acetamiprid, imidacloprid, imidaclothiz,
      nitenpyram, thiacloprid, and thiamethoxam). Moreover, the insect growth regulator
      insecticides (chlorfluazuron, fufenozide, hexaflumuron and tebufenozide)
      exhibited the lowest toxicity to the wasps with an LC50 of 3,383 (2406-5499) to
      30206 (23107-41008) mg ai. L(-1). Risk quotient analysis showed that
      phenylpyrazoles, pyrethroids, insect growth regulators, neonicotinoids (with the
      exception of thiamethoxam), and antibiotics (with the exception of abamectin) are
      classified as safe agents to the parasitoid, while organophosphates and
      carbamates are classified as slightly, moderately, or highly toxic agents to the
      parasitoid. The data presented in this paper provided useful information on the
      selection of compatible insecticides with T. japonicum.

PMID- 22420261
TI  - A degree-day model of sheep grazing influence on alfalfa weevil and crop
      characteristics.
AB  - Domestic sheep (Ovis spp.) grazing is emerging as an integrated pest management
      tactic for alfalfa weevil, Hypera postica (Gyllenhal), management and a degree
      day model is needed as a decision and support tool. In response to this need,
      grazing exclosures with unique degree-days and stocking rates were established at
      weekly intervals in a central Montana alfalfa field during 2008 and 2009.
      Analyses indicate that increased stocking rates and grazing degree-days were
      associated with decreased crop levels of weevil larvae. Larval data collected
      from grazing treatments were regressed against on-site and near-site temperatures
      that produced the same accuracy. The near-site model was chosen to encourage
      producer acceptance. The regression slope differed from zero, had an r2 of 0.83,
      and a root mean square error of 0.2. Crop data were collected to achieve optimal
      weevil management with forage quality and yield. Differences were recorded in
      crude protein, acid and neutral detergent fibers, total digestible nutrients, and
      mean stage by weight. Stem heights differed with higher stocking rates and degree
      days recording the shortest alfalfa canopy height at harvest. The degree-day
      model was validated at four sites during 2010 with a mean square prediction error
      of 0.74. The recommendation from this research is to stock alfalfa fields in the
      spring before 63 DD with rates between 251 and 583 sheep days per hectare (d/ha).
      Sheep should be allowed to graze to a minimum of 106 and maximum of 150 DD before
      removal. This model gives field entomologists a new method for implementing
      grazing in an integrated pest management program.

PMID- 22420262
TI  - Assessment of fennel aphids (Hemiptera: Aphididae) and their predators in fennel
      intercropped with cotton with colored fibers.
AB  - The fennel aphid, Hyadaphis foeniculi (Passerini) (Hemiptera: Aphididae) is a
      major pest of fennel, Foeniculum vulgare Miller in northeast region of Brazil. We
      hypothesize that intercropping can be used as an alternative pest management
      strategy to reduce aphid yield loss in fennel. Thus, we investigated the severity
      of fennel plant damage in relation to infestation by the fennel aphid and
      predation by Cycloneda sanguinea (L.) (Coleoptera: Coccinellidae) (spotless lady
      beetle), green lacewing, Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae),
      and Scymnus spp. (Coleoptera: Coccinellidae) in sole fennel plots and plots of
      fennel intercropped with cotton with colored fibers. The fennel aphid populations
      in nontreated plots were significantly larger in sole fennel plots than in
      intercropped plots. The highest densities of C. sanguinea, green lacewings and
      Scymnus spp., associated with the suppression of fennel aphid populations was
      found in fennel in the intercropping systems. Fennel aphids reduced the fennel
      seed yield by 80% in the sole fennel plots compared with approximately 30% for
      all intercropping systems. The results obtained in this research are of practical
      significance for designing appropriate strategies for fennel aphid control in
      fennel-cotton intercropping systems. In summary, intercropping fennel with cotton
      with colored fibers apparently promoted biocontrol of fennel aphid in fennel.

PMID- 22420263
TI  - A maize line resistant to herbivory constitutively releases (E) -beta
      caryophyllene.
AB  - Various pests, such as those in the order Lepidoptera, frequently feed on young
      maize (Zea mays) plants and pose a significant threat to plant development and
      survival. To manage this problem, maize generates a wide variety of responses to
      attack by pests, from activation of wound-response pathways to the release of
      volatile compounds. Mp708, an inbred line resistant to feeding by the larvae of
      the fall armyworm (Spodoptera frugiperda J.E. Smith Lepidoptera: Noctuidae), has
      been developed through traditional breeding methods, but its underlying
      mechanisms of resistance are still not completely understood. Mp708 has been
      shown to have a moderately high constitutive expression of jasmonic acid (JA)
      before infestation by fall armyworm. However, Tx601, a genotype susceptible to
      feeding by fall armyworm, activates JA pathway only in response to feeding,
      suggesting that Mp708 is "primed" to respond swiftly to an attack. Current
      research indicates that fall armyworm show a lack of preference to feeding on
      Mp708, leading to the hypothesis that volatiles constitutively released by the
      plant may also play an important role in its resistance. Analysis of volatiles
      released by Mp708 and Tx601 in the presence and absence of fall armyworm larvae
      identified (E)-beta-caryophyllene, a terpenoid associated with resistance,
      released constitutively in Mp708. Fall armyworm fed samples of both Mp708 and
      Tx601 showed high transcript number of tps23, the gene responsible for the
      synthesis of (E)-beta-caryophyllene. In addition, fall armyworm larvae show a
      preference for Tx601 whorl tissue over Mp708 tissue, and the dosage of Tx601
      whorl with (E)-beta-caryophyllene repels the fall armyworm.

PMID- 22420264
TI  - Enhanced resistance to four species of Clypeorrhynchan pests in Neotyphodium
      uncinatum infected Italian ryegrass.
AB  - Particular alkaloids produced by Neotyphodium endophytes show toxicity to
      invertebrates. Italian ryegrass (Lolium multiflorum Lamarck) cultivars and
      strains that are symbiotic with Neotyphodium endophytes have been recently
      established in Japan. N. uncinatum-infected Italian ryegrass lines accumulate N
      formylloline, a type of loline alkaloid (1-aminopyrrolizidine) showing
      neurotoxicity to herbivorous insects. This study investigated the toxicity of N
      formylloline and resistance of N. uncinatum-infected Italian ryegrass to vascular
      sap feeding Clypeorrhynchan pests. When four vascular-sap feeding insects:
      Laodelphax striatellus (Fallen) (Homoptera: Delphacidae), Sogatella furcifera
      (Horvath) (Homoptera: Delphacidae), Cicadulina bipunctata (Melichar) (Homoptera:
      Cicadellidae), and Nephotettix cincticeps (Uhler) (Homoptera: Cicadellidae) fed
      on N. uncinatum-infected Italian ryegrass, significant decreases in survival rate
      were observed for three phloem-sap feeders but not for a xylem-sap feeder, N.
      cincticeps. This result suggests an uneven distribution of N-formylloline among
      plant tissues. A potency assay for N-formylloline using a Parafilm feeding sachet
      and a quantitative analysis of N-formylloline in plant showed a concentration
      dependent lethal effect of N-formylloline on all four tested vascular-sap
      feeders. Our results strongly suggest that N. uncinatum-infected plants can
      control some Clypeorrhynchan pests in crop fields.

PMID- 22420265
TI  - Evaluation of aluminum phosphide against wood-destroying insects.
AB  - Aluminum phosphide, a well-known stored grain fumigant, available in solid
      formulation, has shown promise as wood fumigant. This chemical decomposes to
      phosphine when exposed to moisture. The feasibility of fumigant treatment to
      extend the service life of wood was evaluated in a small block test of two wood
      species. Hard wood (Mangifera indica L.) and conifer blocks (Pinus roxburghii
      Sargent) were fumigated with different concentrations (0.05, 0.1, 0.2, 0.4, 0.8,
      and 1.6%) of aluminum phosphide. Fumigated blocks were exposed to Lyctus
      africanus Lesne (Coleoptera; Lyctidae) larvae. Results revealed that aluminum
      phosphide showed complete mortality of Lyctus larvae at 0.2% concentration, that
      is, 0.93 g/m3 retention level. Mean mortality of 74% of Lyctus larvae was
      observed in soft wood blocks fumigated with lowest concentration, that is, 0.05%
      of aluminum phosphide, whereas in hard wood blocks > 85% mortality was observed
      at this concentration.

PMID- 22420266
TI  - Semiochemical emission from individual galleries of the southern pine beetle,
      (Coleoptera: Curculionidae: Scolytinae), attacking standing trees.
AB  - We collected, identified, and quantified volatiles arising from individual
      gallery entrances of the monogamous bark beetle Dendroctonus frontalis
      Zimmermann. Samples were collected while the insects were mass attacking mature
      loblolly pines (Pinus taeda L.) in an established infestation in western
      Mississippi, 1 August through 3 October 2005. Following volatile sample
      collection, the entrances were dissected and categorized according to those that
      1) contained a solitary female (the gallery initiating sex), 2) contained a pair
      that had not yet produced an egg gallery, 3) led to an egg gallery with niches
      and/or eggs, or 4) represented failed attacks (either abandoned or containing
      dead beetles). The greatest mean release rate of the female-produced aggregation
      pheromone components frontalin (74 ng/h) and trans-verbenol (0.35 microg/h) was
      detected from entrances of solitary females, whereas the highest mean quantities
      of the male-produced multifunctional pheromone components endo-brevicomin (18
      ng/h) and verbenone (0.15 microg/h) were detected from entrances of
      preoviposition beetle pairs. Alpha-pinene, a host-produced monoterpene that
      functions as a synergist for the aggregation attractant for D. frontalis, was
      detected from entrances of solitary females and preoviposition pairs at a rate of
      0.6 mg/h, or 3-4 orders of magnitude greater than the insect-produced components
      of the attractant. Our results indicate that the release rates of pheromone
      components used in published field studies of the chemical ecology of D.
      frontalis (generally > 0.1 mg/h) represent thousands of 'attack equivalents' or
      production rates on the scale of a beetle mass attack on a single host.
      Additionally, our data suggest that the loss in attractiveness of host tissue
      fully colonized by D. frontalis is because of the disappearance of attractants
      rather than an increase in inhibitors.

PMID- 22420267
TI  - Responses of Dendroctonus brevicomis (Coleoptera: Curculionidae) in behavioral
      assays: implications to development of a semiochemical-based tool for tree
      protection.
AB  - Currently, techniques for managing western pine beetle, Dendroctonus brevicomis
      LeConte (Coleoptera: Curculionidae, Scolytinae), infestations are limited to tree
      removals (thinning) that reduce stand density and presumably host susceptibility,
      and/or the use of insecticides to protect individual trees. There continues to be
      significant interest in developing an effective semiochemical-based tool for
      protecting trees from D. brevicomis attack, largely as an alternative to
      conventional insecticides. The responses of D. brevicomis to tree volatiles and
      verbenone were documented in eight experiments (trapping assays) conducted over a
      4-yr period in which 88,942 individuals were collected. Geraniol, a tree volatile
      unique to Pinus ponderosa that elicits female-specific antennal responses in D.
      brevicomis, did not affect D. brevicomis behavior. Blends of two green leaf
      alcohols [hexanol + (Z)-3-hexen-1-ol] tested at two release rates (5.0 and 100.0
      mg/d) had no effect on the response of D. brevicomis to attractant-baited traps.
      A nine-component blend [benzaldehyde, benzyl alcohol, guaiacol, nonanal,
      salicylaldehyde, (E)-2-hexenal, (E)-2-hexen-1-ol, (Z)-2-hexen-1-ol, and (-) 
      verbenone; NAVV] and subsequent revisions of this blend disrupted the response of
      D. brevicomis to attractant-baited traps in all experiments. The inhibitory
      effect of a revised five-component blend [nonanal, (E)-2-hexenal, (E)-2-hexen-1
      ol, (Z)-2-hexen-1-ol, and (-)-verbenone; NAVV5] on the response of mountain pine
      beetle, D. ponderosae Hopkins, to attractant-baited traps was also documented.
      Acetophenone significantly reduced D. brevicomis attraction, but was not as
      effective as verbenone alone. Acetophenone increased the effectiveness of NAVV5
      in one of two experiments. Furthermore, by adding acetophenone to NAVV5 we were
      able to remove the aldehydes from NAVV5 without compromising effectiveness,
      resulting in a novel four-component blend [acetophenone, (E)-2-hexen-1-ol + (Z)-2
      hexen-1-ol, and (-)-verbenone; Verbenone Plus]. We discuss the implications of
      these and other results to development of Verbenone Plus as a semiochemical-based
      tool for management of D. brevicomis and D. ponderosae infestations.

PMID- 22420268
TI  - Host plant-related parasitism and host feeding activities of Diglyphus isaea
      (Hymenoptera: Eulophidae) on Liriomyza huidobrensis, Liriomyza sativae, and
      Liriomyza trifolii (Diptera: Agromyzidae).
AB  - Host plant species can affect the behavior and attributes of parasitoids, such as
      host searching, oviposition, and offspring fitness. In this study, parasitism,
      host feeding, and sex ratios of Diglyphus isaea (Walker) (Hymenoptera:
      Eulophidae) on Liriomyza huidobrensis (Blanchard), Liriomyza sativae Blanchard,
      and Liriomyza trifolii (Burgess) (Diptera: Agromyzidae) larvae reared on
      Phaseolus vulgaris L., Pisum sativum L., Solanum lycopersicum L., and Vicia faba
      L. were determined. In no-choice tests, L. huidobrensis had the highest rate of
      parasitism when reared on P. vulgaris (46%), L. sativae when reared on V. faba
      (59%) and P. vulgaris (59%), and L. trifolii when reared on S. lycopersicum
      (68%). Host feeding in no-choice tests ranged between 2% and 36% and was highest
      on L. trifolii reared on V. faba. Results of choice tests showed a significant
      interaction effect for host plant and Liriomyza species on parasitism and host
      feeding. Within plant mixtures, L. sativae reared on P. vulgaris had the highest
      rate of parasitism (31%), followed by L. trifolii on S. lycopersicum (29%) and L.
      huidobrensis on V. faba (28%). Host feeding was highest on L. trifolii reared on
      S. lycopersicum (14%) and lowest on L. huidobrensis reared on P. sativum and S.
      lycopersicum (1%). In some instances, plant mixtures resulted in a higher
      proportion of females of D. isaea than single plant species. The highest
      proportion of females was obtained in plant mixtures on L. huidobrensis and L.
      trifolii on V. faba (71 and 72%, respectively). This study suggests that planting
      crop mixtures can potentially lead to higher proportions of females, thus
      improving parasitism and host feeding, depending on Liriomyza and host plant
      species.

PMID- 22420269
TI  - Field attraction of the vine weevil Otiorhynchus sulcatus to kairomones.
AB  - Root weevils in the genus Otiorhynchus are cited as one of the most important
      pests in the major nursery and small fruit production areas throughout the United
      States, western Canada, and northern Europe. A major problem in combating weevil
      attack is monitoring and timing of control measures. Because of the night
      activity of the adult weevils growers do not observe the emerging weevils in a
      timely manner and oviposition often starts before effective control measures are
      taken. Several vine weevil electroantennogram-active plant volatiles were
      identified from a preferred host plant, Euonymus fortunei. Main compounds evoking
      antennal responses on the weevils' antennae were (Z)-2-pentenol, (E)-2-hexenol,
      (Z)-3-hexenol, methyl benzoate, linalool, (E)-4,8-dimethyl-1,3,7-nonatriene,
      methyl eugenol, and (E, E)-alpha-farnesene. Several of these compounds were
      tested alone and in mixtures on attractiveness for the vine weevil Otiorhynchus
      sulcatus (F.) in field-grown strawberry in Oregon. O. sulcatus were attracted to
      (Z)-2-pentenol (approximately 3 x more than control) and a 1:1 ratio mixture of
      (Z)-2-pentenol and methyl eugenol (4.5 x more than control). This is the first
      report of field-active attractants for O. sulcatus which holds promise for the
      development of new monitoring strategies for growers in the near future.

PMID- 22420270
TI  - Effects of irrigation on the seasonal abundance of Empoasca vitis in north
      Italian vineyards.
AB  - The effect of irrigation on the abundance of Empoasca vitis (Gothe) populations
      was investigated in four vineyards located in northeastern Italy. In two
      experiments, we compared leafhopper population densities in plots irrigated
      (micro-spray irrigation system) or nonirrigated. In another experiment, we
      studied the effect of various irrigation systems on E. vitis populations over two
      successive seasons. In particular, five treatments were compared: control (not
      irrigated), traditional drip system, three types of subirrigation varying in
      distance from the row (40, 135, and 95 cm). In this vineyard, stem water
      potential was monitored with a pressure chamber. E. vitis population densities
      were affected by irrigation, with higher densities of this pest recorded on
      irrigated vines. Highest E. vitis densities were detected in drip irrigation
      plots compared with nonirrigated plots where water stress was highest. Moderate
      water stress (subirrigation plots) was associated with intermediate leafhopper
      densities. Implications for integrated pest management are discussed.

PMID- 22420271
TI  - Olive fruit fly (Diptera: Tephritidae) in California: longevity, oviposition, and
      development in canning olives in the laboratory and greenhouse.
AB  - The biology of olive fruit fly, Bactrocera oleae (Rossi), was studied in the
      laboratory, greenhouse, and in canning olives, Olea europaea L., in relation to
      California regional climates. Adults survived in laboratory tests at constant
      temperatures and relative humidities of 5 degrees C and 83%; 15 degrees C and
      59%; 25 degrees C and 30%; and 35 degrees C and 29% for 15, 6, 3, and 2 d without
      provisions of food and water and for 37, 63, 25, and 4 d with provisions,
      respectively. In a divided greenhouse, adults survived for 8-11 d in the warm
      side (36 degrees C and 31% RH daytime); and in the cool side (26 degrees C and
      63% RH daytime) 10 d without provisions and 203 d with provisions. A
      significantly greater number of adults survived in the cool side than the warm
      side, and with provisions than without. First and last eggs were oviposited in
      olive fruit when females were 6 and 90 d old, respectively. The highest number of
      eggs was 55 per day in 10 olive fruit oviposited by 10 28 d-old females, with
      maximum egg production by 13-37 d-old females. A significantly greater number of
      ovipositional sites occurred in all sizes of immature green fruit when exposed to
      adults in cages for 5 d than 2 d. Adults emerged from fruit with a height of > or
      = 1.0 cm or a volume of > or = 0.2 cm3. More than seven adults per 15 fruit
      emerged from field infested fruit with a height of 1.1 cm and volume of 0.1 cm3.
      Larval length was significantly different among the first, second, and third
      instars and ranged from 0.7 to 1.6, 2.4-4.3, and 4.8-5.6 mm at 14 degrees C; 0.8
      1.1, 1.9-2.9, and 3.9-4.4 mm at 21 degrees C, and 0.7-1.3, 2.4-2.9, and 4.4-4.8
      mm at 26 degrees C, respectively. Survival of pupae to the adult stage was
      significantly lower at 26 degrees C than 14 degrees C or 21 degrees C. The period
      of adult emergence began at 38, 14, and 11 d over a period of 8, 5, and 1 d at
      14, 21, and 26 degrees C, respectively. Findings were related to the occurrence
      and control of California olive fruit fly infestations.

PMID- 22420272
TI  - Economic analysis of emerald ash borer (Coleoptera: Buprestidae) management
      options.
AB  - Emerald ash borer, Agrilus planipennis (Fairmaire) (Coleoptera: Buprestidae),
      plays a significant role in the health and extent of management of native North
      American ash species in urban forests. An economic analysis of management options
      was performed to aid decision makers in preparing for likely future infestations.
      Separate ash tree population valuations were derived from the i-Tree Streets
      program and the Council of Tree and Landscape Appraisers (CTLA) methodology. A
      relative economic analysis was used to compare a control option (do-nothing
      approach, only removing ash trees as they die) to three distinct management
      options: 1) preemptive removal of all ash trees over a 5 yr period, 2) preemptive
      removal of all ash trees and replacement with comparable nonash trees, or 3)
      treating the entire population of ash trees with insecticides to minimize
      mortality. For each valuation and management option, an annual analysis was
      performed for both the remaining ash tree population and those lost to emerald
      ash borer. Retention of ash trees using insecticide treatments typically retained
      greater urban forest value, followed by doing nothing (control), which was better
      than preemptive removal and replacement. Preemptive removal without tree
      replacement, which was the least expensive management option, also provided the
      lowest net urban forest value over the 20-yr simulation. A "no emerald ash borer"
      scenario was modeled to further serve as a benchmark for each management option
      and provide a level of economic justification for regulatory programs aimed at
      slowing the movement of emerald ash borer.

PMID- 22420273
TI  - Baseline toxicity and field efficacy of metaflumizone on Colorado potato beetle
      (Coleoptera: Chrysomelidae).
AB  - Baseline toxicity levels to a novel semicarbazone insecticide, metaflumizone were
      established for 25 field populations of Colorado potato beetle, Leptinotarsa
      decemlineata Say (Coleoptera: Chrysomelidae),from North America. Excluding the
      susceptible laboratory strain, 50% lethal concentrations of metaflumizone ranged
      from 0.57 to 1.31 ppm, while response slopes ranged from 1.92 to 4.24 (average =
      2.93), and were unrelated to the 50% lethal concentration (r = 0.06; P = 0.76).
      Beetle populations with known resistance to the neonicotinoid imidacloprid also
      exhibited the highest LC50 levels to metaflumizone suggesting at least the
      possibility of cross-resistance. Additional experiments using a potato leaf-dip
      bioassay as well as field efficacy evaluations confirmed the high level of
      toxicity of metaflumizone to L. decemlineata and demonstrated a potential benefit
      of tank mixing a low rate of the pyrethroid esfenvalerate with metaflumizone at
      one-tenth the recommended field rate. These research findings confirm that
      metaflumizone is highly active against L. decemlineata larvae and adults and
      could provide an effective alternative insecticide for potato pest management.

PMID- 22420274
TI  - Susceptibility to the Cry1F toxin of field populations of Sesamia nonagrioides
      (Lepidoptera: Noctuidae) in Mediterranean maize cultivation regions.
AB  - Maize hybrids expressing the Cry1F toxin provide efficient control of
      lepidopteran pests. The Mediterranean corn borer, Sesamia nonagrioides (Lefevre),
      is one of the most damaging pests of maize in the Mediterranean basin. In this
      work we firstly determined the efficacy of maize hybrids expressing the Cry1F
      toxin (event TC1507) to control neonates of S. nonagrioides. Leaf tissue feeding
      bioassays revealed that TC1507 maize is highly effective against this pest, and
      the percentage mortality obtained was comparable to that obtained with a Cry1Ab
      expressing maize hybrid (Compa CB, event 176), which is known to be highly
      efficacious against S. nonagrioides. Secondly, interpopulation variation in the
      susceptibility to the Cry1F insecticidal protein was established for nine field
      collected populations of S. nonagrioides (three Spanish, two French, two Italian,
      one Greek, and one Turkish). Estimates of the susceptibility of larvae to the
      Cry1F toxin showed low variability in lethal concentrations and growth inhibition
      concentrations among field populations. Moreover, no significant differences were
      found when they were grouped by geographical areas [Western Mediterranean (Spain
      and France) versus Eastern Mediterranean (Italy, Greece and Turkey)] or by
      history of exposure to Bt plants (Spanish vs. other populations). Therefore, the
      minor differences found in field populations can be attributed to natural
      variation in sensitivity to Cry1F. The importance of establishing baselines of
      susceptibility for resistance detection is discussed. Future changes in
      susceptibility of S. nonagrioides populations to Cry1F could be documented based
      on this baseline data.

PMID- 22420275
TI  - Susceptibility of Ixodes scapularis (Acari: Ixodidae) to Metarhizium brunneum F52
      (Hypocreales: Clavicipitaceae) using three exposure assays in the laboratory.
AB  - An emulsifiable concentrate (EC) and granular (G) formulation of the
      entomopathogenic fungus, Metarhizium brunneum strain F52 (formerly Metarhizium
      anisopliae strain F52) were tested against unfed adults and nymphs of Ixodes
      scapularis Say in the laboratory. Three exposure methods; dip, surface contact,
      and direct spray application, and three exposure time intervals (3, 30, and 300
      min) were used to evaluate the EC formulation. Application rates ranged from 2.6
      x 10(2) to 2.6 x 10(8) conidia/cm2. The surface treatment was used for granular
      formulation with concentrations ranging from 2.3 x 10(5) to 2.3 x 10(7)
      conidia/cm2 for same three exposure times. Both the EC and G formulations of this
      fungus were highly pathogenic against I. scapularis adults and nymphs. Logistic
      regression analysis found formulation, spore concentration, time of exposure, and
      observation period were significant or highly significant factors influencing
      tick mortality. For adult I. scapularis, the spray application with the EC
      formulation of M. brunneum F52 resulted in a lower LC50 (5.9 x 10(4) conidia/cm2)
      at 30 min than surface exposure to the EC (LC50 = 1.3 x 10(6) conidia/cm2) or G
      formulation (LC50 = 8.1 x 10(5) conidia/cm2). At higher concentrations, fungal
      activity was evident in adult I. scapularis held at 5 degrees C suggesting the
      fungus may provide control in the cooler fall season. While the observed
      pathogenicity of a fungus against ticks can be dependent upon the bioassay
      assessment, we found nymphs and adults of I. scapularis to be highly susceptible
      to M. brunneum F52, regardless of the exposure method used.

PMID- 22420276
TI  - Polymorphism and methylation of four genes expressed in salivary glands of
      Russian wheat aphid (Homoptera: Aphididae).
AB  - DNA methylation is a general epigenetic mechanism for plants, animals, and fungi
      to adapt to environmental variation. Two biotypes of the Russian wheat aphid
      (Diuraphis noxia), Biotype 1 and Biotype 2, have different virulence to host
      plants. In this study, in addition to a high polymorphism, DNA methylation at
      cytosines were observed in genomic fragments of four genes in Biotype 1 and
      Biotype 2, after the genomic DNA was treated with sodium bisulfite. These genes
      presumably encode proteins and enzymes in salivary glands of aphids. The two
      Biotype 1 showed different methylation levels, that is, Biotype 1 showed a higher
      methylation on the four genes. Two thirds of methyl cytosines were in a sequence
      context of CHH (H = A, C, or T). Some polymorphism and methylation sites were
      located at important positions in terms of enzyme function, such as close to
      catalytic residues or inhibitor binding residues. These findings may provide
      clues to explore the evolutionary mode between Russian wheat aphid virulence and
      resistance genes of host plants.

PMID- 22420277
TI  - Use of mitochondrial cytochrome oxidase I polymerase chain reaction-restriction
      fragment length polymorphism for identifying subclades of Bemisia tabaci
      Mediterranean group.
AB  - The Mediterranean group (commonly known as Q biotype; hereafter MED) of the
      sweetpotato whitefly, Bemisia tabaci (Gennadius), originated in the Mediterranean
      region, but it now has been found in at least 10 countries outside the
      Mediterranean. Collections of B. tabaci from some of these countries exhibit
      different pest behaviors and pesticide resistance characteristics, yet all may be
      classified as MED. A phylogenetic analysis of 120 mitochondrial cytochrome
      oxidase I (mtCOI) sequences (JN966761-JN966880) of MED whiteflies collected in
      Arizona and of 417 retrieved from the GenBank database resolves the MED into five
      subclades, designated as Q1-Q5. Only subclades Q1 and Q2 have been detected in
      the United States. Q1 and the other four subclades (Q2-Q5) differ in the number
      or position of the AluI recognition sites. Based on the differences in the AluI
      recognition sites reported here and the previously reported differences in VspI
      recognition sites, we developed a simple diagnostic technique to identify
      subclades Q1-Q5 by using mtCOI polymerase chain reaction (PCR)-restriction
      fragment-length polymorphism (RFLP). A test of a worldwide collection of
      whiteflies demonstrates that this combination mtCOIPCR-RFLP technique can
      reliably distinguish not only the MED from the Middle East-Asia Minor 1 group but
      also the Q1 from any of the other four MED subclades.

PMID- 22420278
TI  - Soybean aphid (Hemiptera: Aphididae) development on soybean with Rag1 alone, Rag2
      alone, and both genes combined.
AB  - Aphis glycines Matsumura (Hemiptera: Aphididae) can reduce the yield of aphid
      susceptible soybean (Glycine max (L.) Merrill) cultivars. The Rag1 and Rag2 genes
      conferresistance to some biotypes of A. glycines. These genes individually can
      limit population growth of A. glycines and prevent yield loss. The impact of
      these genes when combined is not known. We compared the development of A.
      glycines on soybean with Rag1 alone (R1/S2), Rag2 alone (S1/R2), both genes
      combined (R1/R2), or neither gene (S1/S2). In addition, we determined the impact
      of different levels of aphid infestation on seed yield. The genotypes were grown
      in cages and artificially infested with A. glycines to achieve five treatment
      levels: aphid-free, 675 aphids per plant, 25,000 cumulative aphid days (CAD)
      (25K), 50,000 CAD (50K), and 75,000 CAD (75K). The S1/S2 line reached the 50K
      treatment, but did not reach the 75K treatment. Aphid development on R1/S2 and
      S1/R2 soybeans after two infestations reached a maximum of 25K. The maximum
      treatment reached on R1/R2 was only 675 aphids per plant after two infestations,
      at which there was no significant yield reduction when compared with the aphid
      free treatment. The maximum yield reduction of S1/S2 was 27% at 50K treatment
      compared with 2% for R1/S2 and 12% for S1/R2 at the 25K treatment. Our results
      indicated that for A. glycines used in our study, cultivars with both Rag1 and
      Rag2 had less aphid exposure and less yield reduction than soybeans with only one
      resistant gene.

PMID- 22420279
TI  - Spatial distribution of Aphis glycines (Hemiptera: Aphididae): a summary of the
      suction trap network.
AB  - The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is an
      economically important pest of soybean, Glycine max (L.) Merrill, in the United
      States. Phenological information of A. glycines is limited; specifically, little
      is known about factors guiding migrating aphids and potential impacts of long
      distance flights on local population dynamics. Increasing our understanding of A.
      glycines population dynamics may improve predictions of A. glycines outbreaks and
      improve management efforts. In 2005 a suction trap network was established in
      seven Midwest states to monitor the occurrence of alates. By 2006, this network
      expanded to 10 states and consisted of 42 traps. The goal of the STN was to
      monitor movement of A. glycines from their overwintering host Rhamnus spp. to
      soybean in spring, movement among soybean fields during summer, and emigration
      from soybean to Rhamnus in fall. The objective of this study was to infer
      movement patterns of A. glycines on a regional scale based on trap captures, and
      determine the suitability of certain statistical methods for future analyses.
      Overall, alates were not commonly collected in suction traps until June. The most
      alates were collected during a 3-wk period in the summer (late July to mid
      August), followed by the fall, with a peak capture period during the last 2 wk of
      September. Alate captures were positively correlated with latitude, a pattern
      consistent with the distribution of Rhamnus in the United States, suggesting that
      more southern regions are infested by immigrants from the north.

PMID- 22420280
TI  - Estimating the influence of population density and dispersal behavior on the
      ability to detect and monitor Agrilus planipennis (Coleoptera: Buprestidae)
      populations.
AB  - Emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), a
      phloem-feeding pest of ash (Fraxinus spp.) trees native to Asia, was first
      discovered in North America in 2002. Since then, A. planipennis has been found in
      15 states and two Canadian provinces and has killed tens of millions of ash
      trees. Understanding the probability of detecting and accurately delineating low
      density populations of A. planipennis is a key component of effective management
      strategies. Here we approach this issue by 1) quantifying the efficiency of
      sampling nongirdled ash trees to detect new infestations of A. planipennis under
      varying population densities and 2) evaluating the likelihood of accurately
      determining the localized spread of discrete A. planipennis infestations. To
      estimate the probability a sampled tree would be detected as infested across a
      gradient of A. planipennis densities, we used A. planipennis larval density
      estimates collected during intensive surveys conducted in three recently infested
      sites with known origins. Results indicated the probability of detecting low
      density populations by sampling nongirdled trees was very low, even when
      detection tools were assumed to have three-fold higher detection probabilities
      than nongirdled trees. Using these results and an A. planipennis spread model, we
      explored the expected accuracy with which the spatial extent of an A. planipennis
      population could be determined. Model simulations indicated a poor ability to
      delineate the extent of the distribution of localized A. planipennis populations,
      particularly when a small proportion of the population was assumed to have a
      higher propensity for dispersal.

PMID- 22420281
TI  - Effectiveness of sulfuryl fluoride for control of different life stages of stored
      product psocids (Psocoptera).
AB  - With the phase-out and impending ban of methyl bromide, sulfuryl fluoride is
      among the most promising alternative fumigant insecticides for control of stored
      product insect pests. It has been evaluated for control of several stored-product
      insect pests, but there are few data available on its efficacy for control of
      stored-product psocids (Psocoptera). We evaluated sulfuryl fluoride for control
      of different life stages of the psocids Liposcelis paeta Pearman, L. entomophila
      (Enderlein), L. bostrychophila Badonnel, L. decolor Pearman, and Lepinotus
      reticulatus Enderlein (Trogiidae) in 48-hr trials at 27.5 degrees C. Adults and
      nymphs were susceptible to sulfuryl fluoride. Complete (100%) adult and nymphal
      mortality was recorded at concentrations between 4 and 8 g/m3, except for L.
      decolor for which all adults were only killed at 24 g/m3. Eggs were tolerant to
      sulfuryl fluoride. Complete egg mortality was achieved at 24 and 72 g/m3 for L.
      reticulatus and L. decolor, respectively. Survival of L. paeta eggs was recorded
      even after exposure to 96 g/m3. Given that the highest United States label
      concentration for sulfuryl fluoride for a 48-h exposure interval is 31.25 g/m3,
      our study indicates that high doses and/or longer exposures are needed for
      complete mortality of eggs of L. decolor and L. paeta. Moreover, the present work
      suggests that there is considerable variation in efficacy of sulfuryl fluoride
      for control of different psocid species.

PMID- 22420282
TI  - Effects of the heavy metal Cu2+ on growth, development, and population dynamics
      of Spodoptera litura (Lepidoptera: Noctuidae).
AB  - Spodoptera litura (F.) larvae were fed with artificial food containing four
      different concentrations of copper (25, 50, 100, and 200 mg/kg). Copper affected
      growth, development, and population dynamics of late instar larvae. Our results
      indicate that the fourth and fifth instar survival rates were significantly
      reduced at 50-200 mg/kg copper (Cu2+). Moreover, all the Cu2+ treatments
      significantly reduced pupation and moth emergence rates in a dose-dependent
      manner. Larvae fed 25 or 50 mg/kg Cu2+ showed significant reductions in
      development period compared with non-Cu controls, and the pupation duration of
      animals fed 200 mg/kg was significantly longer than in non-Cu controls. All Cu2+
      concentrations significantly reduced individual pupal weights compared with
      controls. In addition, Cu2+ at some concentrations significantly affected
      fertility parameters, such as doubling population time (DT), the net reproduction
      rate (R(o)), the mean generation time (T), the intrinsic rate of increase (r(m)),
      and the finite increase rate (A). Our study demonstrates that low concentrations
      of Cu2+ in the diet (25 and 50 mg/kg) shorten the generation time by 4-5 d,
      whereas higher Cu2+ concentrations (100 and 200 mg/kg) increase DT for 1-2 d.

PMID- 22420283
TI  - Issues that impact caseloads.

PMID- 22420284
TI  - The process of staffing analysis.

PMID- 22420285
TI  - Standard circumstances and vital goals: comments on Venkatapuram's critique.
AB  - This article is a reply to Venkatapuram's critique in his article Health, Vital
      Goals, Capabilities, this volume. I take issue mainly with three critical points
      put forward by Venkatapuram with regard to my theory of health. (1) I deny that
      the contents of my vital goals are relative to each community or context, as
      Venkatapuram claims. There is no conceptual connection at all between standard
      circumstances and vital goals, as I understand these concepts. (2) Venkatapuram
      notes that I stop short of filling the framework of vital goals with any content
      and thereby make my concept of health less concrete. I reply that some vital
      goals are indeed universal, viz. the ones which are necessary conditions for
      survival. Many other vital goals are individual and cannot therefore be included
      in a universal list. (3) Venkatapuram claims that my definition of vital goals is
      too broad, since it entails that some persons without any disease can be regarded
      as ill. However, in my understanding health is a relational concept from a state
      of complete health to a state of maximal illness. In this framework, a minor
      reduction of a state of complete health does not entail illness. This article
      also contains a comparison between my theory of health and Martha Nussbaum's
      theory of capabilities for dignity.

PMID- 22420286
TI  - Polyplexes traffic through caveolae to the Golgi and endoplasmic reticulum en
      route to the nucleus.
AB  - The cellular machinery involved in the internalization of nonviral gene carriers
      and their subsequent trafficking to the nucleus directly impacts their
      therapeutic efficiency. Hence, identifying key endocytic pathways and organelles
      that contribute to the successful transfer of polyplexes to the nucleus generates
      new opportunities for improving carrier design. Previously, we showed that
      histone H3 tail peptides encoding a sequence known to participate in chromatin
      activation exhibit synergistic gene delivery activity with poly(ethylenimine)
      (PEI). Polyplexes containing H3 and PEI exhibited a reduced dependence on
      endocytic pathways that trafficked to lysosomes, and had enhanced sensitivity to
      an inhibitor associated with retrograde trafficking through the Golgi apparatus.
      Thus, we sought to determine whether caveolar uptake and transport through the
      Golgi and/or endoplasmic reticulum (ER) preceded nuclear delivery. By the use of
      a panel of chemical endocytic inhibitors, we determined that H3 polyplexes
      utilized caveolar pathways to a greater degree than PEI polyplexes. Caveolae
      mediated endocytosis was found to be a productive route for gene expression by
      the H3/PEI-pDNA polyplexes, consistent with previous studies of polymer-mediated
      gene delivery. Additionally, the polyplexes substantially colocalized within the
      ER after only 5 min of incubation, and utilized retrograde Golgi-to-ER pathways
      at levels similar to pathogens known to traffic by these routes during infection.
      The results of this study have expanded our understanding of how caveolar
      polyplexes are trafficked to cell nuclei, and provide new evidence for the role
      of Golgi-ER pathways in transfection. These findings suggest new design criteria
      and opportunities to stragetically target nonviral gene delivery vehicles.

PMID- 22420290
TI  - Dietary nitrate and nitrite intake and non-Hodgkin lymphoma survival.
AB  - Nitrate and nitrite are precursors in the formation of N-nitroso compounds. We
      recently found a 40% increased risk of NHL with higher dietary nitrite intake and
      significant increases in risk for follicular and T-cell lymphoma. It is possible
      that these compounds also affect NHL prognosis by enhancing cancer progression in
      addition to development by further impairing immune system function. To test the
      hypothesis that nitrate and nitrite intake affects NHL survival, we evaluated the
      association in study participants that have been followed post-disease diagnosis
      in a population-based case-control study among women in Connecticut. We did not
      observe a significant increasing trend of mortality for NHL overall or by subtype
      for nitrate or nitrite intake for deaths from NHL or death from any cause,
      although a borderline significant protective trend was observed for follicular
      lymphoma with increasing nitrate intake. We did not identify a difference in
      overall survival for nitrate (P = 0.39) or for nitrite (P = 0.66) or for NHL
      specific survival for nitrate (P = 0.96) or nitrite (P = 0.17). Thus, our null
      findings do not confer support for the possibility that dietary nitrate and
      nitrite intake impacts NHL survival by promoting immune unresponsiveness.

PMID- 22420291
TI  - Comparison of four techniques of arthrocentesis of the lateral compartment of the
      femorotibial joint of the horse.
AB  - REASONS FOR PERFORMING STUDY: Clinical experiences indicate that centesis of the
      lateral compartment of the femorotibial joint is often unsuccessful. OBJECTIVE:
      To determine the accuracy of 2 published and 2 unpublished techniques of centesis
      of the lateral compartment of the femorotibial joint. HYPOTHESIS: It was
      hypothesised that a drug can be administered into the lateral compartment of the
      femorotibial joint via a diverticulum of this joint that surrounds the medial
      aspect of the long digital extensor tendon and that this technique is more
      accurate than described techniques of centesis of this compartment. METHODS:
      Twenty-four stifles of 12 horses were divided equally into 4 groups and a
      radiocontrast medium injected into the lateral compartment of the femorotibial
      joint of each group using a hypodermic needle inserted: 1) caudal to the lateral
      patellar ligament and proximal to the tibial plateau, 2) caudal to the long
      digital extensor tendon and proximal to the tibial plateau, 3) between the long
      digital extensor tendon and bone of the extensor groove of the tibia or 4)
      directly through the long digital extensor tendon until it contacted bone. Twelve
      veterinary students who had no experience using any of these techniques performed
      the injections. Accuracy of each technique was determined by examining
      radiographs obtained after injecting the contrast medium. RESULTS: The most
      successful technique for arthrocentesis was by inserting a needle through the
      long digital extensor tendon. This approach was successful in all attempted
      cases, whilst other techniques had lower rates of success. CONCLUSIONS: The
      lateral compartment of the femorotibial joint can be accessed accurately by
      inserting a needle through the long digital extensor tendon as it lies within the
      extensor groove. Other techniques may not be as accurate for clinicians
      inexperienced in arthrocentesis of the lateral compartment of the femorotibial
      joint.

PMID- 22420292
TI  - The risk of passive regurgitation during general anaesthesia in a population of
      referred dogs in the UK.
AB  - OBJECTIVE: To evaluate the risk of passive regurgitation during anaesthesia, and
      to identify major factors associated with this in dogs attending the Queen Mother
      Hospital for Animals (QMHA), the Royal Veterinary College. STUDY DESIGN: A case
      control study nested within the cohort of dogs undergoing anaesthesia with
      inhalation agents. ANIMAL POPULATION: All dogs undergoing general anaesthesia at
      the referral hospital between October 2006 and September 2008 (4271 cases).
      METHODS: All dogs anaesthetized at the QMHA during the study period were
      included. Regurgitating cases were defined as dogs for which reflux material was
      observed at the external nares or in the mouth, either during anaesthesia or
      before return to normal consciousness immediately after general anaesthesia. The
      risk of regurgitation was estimated and risk factors for regurgitation were
      evaluated with multivariable logistic regression (p < 0.05). RESULTS: The overall
      risk of regurgitation was 0.96% (41 cases out of 4271 anaesthetics, 95%
      confidence interval [95% CI] 0.67-1.25%). Exclusion of animals where pre-existing
      disease was considered a contributing factor to regurgitation (n = 14) resulted
      in a risk of passive regurgitation of 0.63% (27 cases of 4257 anaesthetics, 95%
      CI 0.40-0.87%). In the multivariable logistic regression model, procedure and
      patient weight were significantly associated with regurgitation. Dogs undergoing
      orthopaedic surgery were 26.7 times more likely to regurgitate compared to dogs
      undergoing only diagnostic procedures. Dogs weighing more than 40 kg were
      approximately five times more likely to regurgitate than those weighing <20 kg.
      CONCLUSIONS AND CLINICAL RELEVANCE: This study highlights the rare but important
      occurrence of perioperative regurgitation and identifies that dogs undergoing
      orthopaedic procedures, and those weighing more than 40 kg, are particularly at
      risk. Further work is required to evaluate the reasons for these observations.

PMID- 22420293
TI  - Everolimus-eluting ABSORB bioresorbable vascular scaffold: present and future
      perspectives.
AB  - Everolimus-eluting ABSORB bioresorbable vascular scaffolds represent a novel
      approach that provides transient vessel support with drug-delivery capability
      without the long-term limitations of the metallic drug-eluting stents (DESs). The
      technology has the potential to overcome many of the safety concerns associated
      with metallic DESs and possibly even convey further clinical benefit. In
      particular the scaffold is designed for providing a short-term lumen support (up
      to 6-12 months) and for thereafter being completely bioresorbed, eliminating the
      permanent caging typical of the metallic DES. The first clinical studies testing
      this device in a small number of patients have shown very promising results with
      good clinical outcome up to 5 years' follow-up, highlighting important
      morphological and functional modifications at the scaffolded segment level, such
      as late lumen enlargement and recuperation of a normal vasoreactivity. A
      randomized trial, comparing ABSORB with the Xience Prime stent, will evaluate the
      efficacy and safety of this device in a wide population.

PMID- 22420294
TI  - Aplastic anaemia and PNH transformation with deposition of liver iron.

PMID- 22420295
TI  - Anti-TCRbeta mAb induces long-term allograft survival by reducing antigen
      reactive T cells and sparing regulatory T cells.
AB  - TCR specific antibodies may modulate the TCR engagement with antigen-MHC
      complexes, and in turn regulate in vivo T cell responses to alloantigens. Herein,
      we found that in vivo administration of mAbs specific for mouse TCRbeta (H57
      597), TCRalpha or CD3 promptly reduced the number of CD4(+)  and CD8(+)  T cells
      in normal mice, but H57-597 mAb most potently increased the frequency of CD4(+)
      Foxp3(+)  Treg cells. When mice were injected with staphylococcal enterotoxin B
      (SEB) superantigen and H57-597 mAb, the expansion of SEB-reactive Vbeta8(+)  T
      cells was completely abrogated while SEB-nonreactive Vbeta2(+)  T cells remained
      unaffected. More importantly, transient H57-597 mAb treatment exerted long
      lasting effect in preventing T cell responses to alloantigens, and produced long
      term cardiac allograft survival (>100 days) in 10 out of 11 recipients. While
      Treg cells were involved in maintaining donor-specific long-term graft survival,
      T cell homeostasis recovered over time and immunity was retained against third
      party allografts. Moreover, transient H57-597 mAb treatment significantly
      prolonged survival of skin allografts in naive recipients as well as heart
      allografts in skin-sensitized recipients. Thus, transient modulation of the
      TCRbeta chain by H57-597 mAb exhibits potent, long-lasting therapeutic effects to
      control alloimmune responses.

PMID- 22420297
TI  - An asymptomatic, progressive, ulcerative nodule over the anterolateral surface of
      the left upper arm.

PMID- 22420296
TI  - Observing a model ion channel gating action in model cell membranes in real time
      in situ: membrane potential change induced alamethicin orientation change.
AB  - Ion channels play crucial roles in transport and regulatory functions of living
      cells. Understanding the gating mechanisms of these channels is important to
      understanding and treating diseases that have been linked to ion channels. One
      potential model peptide for studying the mechanism of ion channel gating is
      alamethicin, which adopts a split alpha/3(10)-helix structure and responds to
      changes in electric potential. In this study, sum frequency generation
      vibrational spectroscopy (SFG-VS), supplemented by attenuated total reflectance
      Fourier transform infrared spectroscopy (ATR-FTIR), has been applied to
      characterize interactions between alamethicin (a model for larger channel
      proteins) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid
      bilayers in the presence of an electric potential across the membrane. The
      membrane potential difference was controlled by changing the pH of the solution
      in contact with the bilayer and was measured using fluorescence spectroscopy. The
      orientation angle of alamethicin in POPC lipid bilayers was then determined at
      different pH values using polarized SFG amide I spectra. Assuming that all
      molecules adopt the same orientation (a delta distribution), at pH = 6.7 the
      alpha-helix at the N-terminus and the 3(10)-helix at the C-terminus tilt at about
      72 degrees  (theta(1)) and 50 degrees  (theta(2)) versus the surface normal,
      respectively. When pH increases to 11.9, theta(1) and theta(2) decrease to 56.5
      degrees  and 45 degrees , respectively. The delta distribution assumption was
      verified using a combination of SFG and ATR-FTIR measurements, which showed a
      quite narrow distribution in the angle of theta(1) for both pH conditions. This
      indicates that all alamethicin molecules at the surface adopt a nearly identical
      orientation in POPC lipid bilayers. The localized pH change in proximity to the
      bilayer modulates the membrane potential and thus induces a decrease in both the
      tilt and the bend angles of the two helices in alamethicin. This is the first
      reported application of SFG to the study of model ion channel gating mechanisms
      in model cell membranes.

PMID- 22420300
TI  - Reasons for binge drinking among undergraduate students: An application of
      behavioural reasoning theory.
AB  - OBJECTIVES: This study sought to apply behavioural reasoning theory (BRT) to the
      prediction of undergraduate students' binge drinking intentions and behaviour.
      The reasons students use to justify and defend binge drinking may provide
      important information on motivations underlying such behaviour. METHODS:
      Undergraduate students (N= 265) completed questionnaires assessing their reasons
      for and against binge drinking, attitude, subjective norm, perceived behavioural
      control, intention, and past behaviour. Frequency of binge drinking was assessed
      at 1-week follow-up (N= 172). RESULTS: A series of path analyses were conducted
      to assess the direct and indirect effects of the BRT variables on binge drinking
      intentions and behaviour. The variables under consideration accounted for 80% of
      the variance in binge drinking intentions (with past behaviour, reasons for binge
      drinking, and attitude having significant direct effects on intention), and 34%
      of the variance in binge drinking at 1-week follow-up (with past behaviour,
      perceived behavioural control, and intention having significant direct effects on
      future behaviour). Additional regression analyses revealed that respondents who
      strongly endorsed being sociable and having fun as reasons for binge drinking
      were more likely to intend to engage in binge drinking over the subsequent week.
      CONCLUSIONS: The results provide support for BRT as a framework for understanding
      undergraduate students' binge drinking intentions and behaviour, and suggest that
      interventions need to focus on the social reasons for engaging in binge drinking
      in undergraduate students.

PMID- 22420298
TI  - The prolactin gene: a paradigm of tissue-specific gene regulation with complex
      temporal transcription dynamics.
AB  - Transcription of numerous mammalian genes is highly pulsatile, with bursts of
      expression occurring with variable duration and frequency. The presence of this
      stochastic or 'noisy' expression pattern has been relatively unexplored in tissue
      systems. The prolactin gene provides a model of tissue-specific gene regulation
      resulting in pulsatile transcription dynamics in both cell lines and endocrine
      tissues. In most cell culture models, prolactin transcription appears to be
      highly variable between cells, with differences in transcription pulse duration
      and frequency. This apparently stochastic transcription is constrained by a
      transcriptional refractory period, which may be related to cycles of chromatin
      remodelling. We propose that prolactin transcription dynamics result from the
      summation of oscillatory cellular inputs and by regulation through chromatin
      remodelling cycles. Observations of transcription dynamics in cells within
      pituitary tissue show reduced transcriptional heterogeneity and can be grouped
      into a small number of distinct patterns. Thus, it appears that the tissue
      environment is able to reduce transcriptional noise to enable coordinated tissue
      responses to environmental change. We review the current knowledge on the complex
      tissue-specific regulation of the prolactin gene in pituitary and extra-pituitary
      sites, highlighting differences between humans and rodent experimental animal
      models. Within this context, we describe the transcription dynamics of prolactin
      gene expression and how this may relate to specific processes occurring within
      the cell.

PMID- 22420299
TI  - Constitutive gray hair in mice induced by melanocyte-specific deletion of c-Myc.
AB  - c-Myc is involved in the control of diverse cellular processes and implicated in
      the maintenance of different tissues including the neural crest. Here, we report
      that c-Myc is particularly important for pigment cell development and
      homeostasis. Targeting c-Myc specifically in the melanocyte lineage using the
      floxed allele of c-Myc and Tyr::Cre transgenic mice results in a congenital gray
      hair phenotype. The gray coat color is associated with a reduced number of
      functional melanocytes in the hair bulb and melanocyte stem cells in the hair
      bulge. Importantly, the gray phenotype does not progress with time, suggesting
      that maintenance of the melanocyte through the hair cycle does not involve c-Myc
      function. In embryos, at E13.5, c-Myc-deficient melanocyte precursors are
      affected in proliferation in concordance with a reduction in numbers, showing
      that c-Myc is required for the proper melanocyte development. Interestingly,
      melanocytes from c-Myc-deficient mice display elevated levels of the c-Myc
      paralog N-Myc. Double deletion of c-Myc and N-Myc results in nearly complete loss
      of the residual pigmentation, indicating that N-Myc is capable of compensating
      for c-Myc loss of function in melanocytes.

PMID- 22420301
TI  - The effects of a regional telepathology project: a study protocol.
AB  - BACKGROUND: Telepathology, which is an emerging form of telemedicine in Canada,
      is defined as the electronic transmission of pathological images, usually derived
      from microscopes, from one location to another. There are various applications of
      telepathology, including case referral for an expert opinion, provision of an
      emergency service in the absence of a resident pathologist, and education. Until
      now, there has been relatively little use of telepathology for core diagnostic
      services in the absence of a local pathologist, but this practice is likely to
      increase in the future. The Laval University Integrated Health Network is in the
      process of deploying a telepathology system, primarily to provide an
      intraoperative frozen section service to small hospitals in sparsely populated
      areas which are experiencing a severe shortage of on-site pathologists. The
      telepathology project involves 17 hospitals located in five regions of eastern
      Quebec, Canada. This paper describes the study protocol that will be used to
      evaluate the benefits associated with the project. METHODS/DESIGN: A panel of
      experts was first assembled by Canada Health Infoway to agree on a set of
      benefits indicators that could be applied to all telepathology projects across
      Canada. Using the set of indicators as an input, we have developed a three-step
      study protocol. First, a survey questionnaire will be distributed to appraise the
      way pathologists, pathology technologists and surgeons perceive the telepathology
      system and its impacts. Second, a series of semi-structured interviews will be
      conducted with project leaders and telepathology users at sites that are
      representative of all the hospitals in the Laval University Integrated Health
      Network. The overall aim is to better understand the expected and unexpected
      effects of telepathology on health care professionals and patients as well as on
      the regional organization and delivery of care services. Finally, a pre-post
      design using secondary data is proposed to evaluate a wide array of tangible
      benefits to the patients, the health care providers, the hospitals, and the
      region as a whole. DISCUSSION: The Laval University Integrated Health Network's
      telepathology project is expected to yield positive and significant results that
      are relevant internationally. Our findings will provide valuable information on
      the nature and extent of benefits associated with telepathology systems intended
      to provide an intraoperative frozen section service to remote hospitals
      experiencing a shortage of specialists.

PMID- 22420302
TI  - Sex-dimorphic landing mechanics and their role within the noncontact ACL injury
      mechanism: evidence, limitations and directions.
AB  - Anterior cruciate ligament (ACL) injuries continue to present in epidemic-like
      proportions, carrying significant short- and longer-term debilitative effects.
      With females suffering these injuries at a higher rate than males, an abundance
      of research focuses on delineating the sex-specific nature of the underlying
      injury mechanism. Examinations of sex-dimorphic lower-limb landing mechanics are
      common since such factors are readily screenable and modifiable. The purpose of
      this paper was to critically review the published literature that currently
      exists in this area to gain greater insight into the aetiology of ACL injuries in
      females and males. Using strict search criteria, 31 articles investigating sex
      based differences in explicit knee and/or hip landing biomechanical variables
      exhibited during vertical landings were selected and subsequently examined. Study
      outcomes did not support the generally accepted view that significant sex-based
      differences exist in lower-limb landing mechanics. In fact, a lack of agreement
      was evident in the literature for the majority of variables examined, with no sex
      differences evident when consensus was reached. The one exception was that women
      were typically found to land with greater peak knee abduction angles than males.
      Considering knee abduction increases ACL loading and prospectively predicts
      female ACL injury risk, its contribution to sex-specific injury mechanisms and
      resultant injury rates seems plausible. As for the lack of consensus observed for
      most variables, it may arise from study-based variations in test populations and
      landing tasks, in conjunction with the limited ability to accurately measure
      lower-limb mechanics via standard motion capture methods. Regardless, laboratory
      based comparisons of male and female landing mechanics do not appear sufficient
      to elucidate causes of injury and their potential sex-specificity. Sex-specific
      in vivo joint mechanical data, if collected accurately, may be more beneficial
      when used to drive models (e.g., cadaveric and computational) that can
      additionally quantify the resultant ACL load response. Without these steps, sex
      dimorphic landing mechanics data will play a limited role in identifying the
      aetiology of ACL injuries in women and men.

PMID- 22420303
TI  - The impact of beta-blocker therapy on anemia after traumatic brain injury.
AB  - BACKGROUND: An increase in endogenous catecholamine levels after traumatic brain
      injury (TBI) is well described. Animal studies suggest that postinjury anemia is
      exacerbated by a persistent hyperadrenergic state. This study aims to determine
      if beta-blocker (BB) exposure affects anemia after TBI. STUDY DESIGN AND METHODS:
      We reviewed a Level I trauma registry for patients with TBI, examining markers of
      anemia between patients who received BB with those who did not. RESULTS: A total
      of 174 patients were exposed to BB (BB+) and 245 were not exposed (BB-). The mean
      age in the BB+ group was 50 years (vs. 36 years in BB- group, p < 0.001). The
      mean injury severity score was 33.6 for the BB+ group (vs. 30.8 for BB- group, p
      = 0.01). While BB+ patients were more likely to receive a transfusion (60.9% vs.
      35.1%, p < 0.001), BB+ patients reached their nadir hemoglobin (Hb) at a later
      day of hospitalization and their rate of decrease in Hb was significantly slower
      (both p < 0.001). Choosing Hb cutoffs for anemia of both 7 and 10 g/dL, Kaplan
      Meier demonstrated a significant delay in time to anemia. CONCLUSION: This study
      suggests beta-blockade delays anemia after TBI. Elaboration of this effect may
      demonstrate an additional benefit of beta-blockade after head injury.

PMID- 22420304
TI  - The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional
      recovery after spinal cord injury.
AB  - BACKGROUND: Chondroitin sulfate proteoglycans are major inhibitory molecules for
      neural plasticity under both physiological and pathological conditions. The
      chondroitin sulfate degrading enzyme chondroitinase ABC promotes functional
      recovery after spinal cord injury, and restores experience-dependent plasticity,
      such as ocular dominance plasticity and fear erasure plasticity, in adult
      rodents. These data suggest that the sugar chain in a proteoglycan moiety is
      essential for the inhibitory activity of proteoglycans. However, the significance
      of the core protein has not been studied extensively. Furthermore, considering
      that chondroitinase ABC is derived from bacteria, a mammalian endogenous enzyme
      which can inactivate the proteoglycans' activity is desirable for clinical use.
      METHODS: The degradation activity of ADAMTS-4 was estimated for the core proteins
      of chondroitin sulfate proteoglycans, that is, brevican, neurocan and phosphacan.
      To evaluate the biological significance of ADMATS-4 activity, an in vitro neurite
      growth assay and an in vivo neuronal injury model, spinal cord contusion injury,
      were employed. RESULTS: ADAMTS-4 digested proteoglycans, and reversed their
      inhibition of neurite outgrowth. Local administration of ADAMTS-4 significantly
      promoted motor function recovery after spinal cord injury. Supporting these
      findings, the ADAMTS-4-treated spinal cord exhibited enhanced axonal
      regeneration/sprouting after spinal cord injury. CONCLUSIONS: Our data suggest
      that the core protein in a proteoglycan moiety is also important for the
      inhibition of neural plasticity, and provides a potentially safer tool for the
      treatment of neuronal injuries.

PMID- 22420305
TI  - Highly malignant behavior of a murine oligodendrocyte precursor cell line
      following transplantation into the demyelinated and nondemyelinated central
      nervous system.
AB  - Understanding the basic mechanisms that control CNS remyelination is of direct
      clinical relevance. Suitable model systems include the analysis of naturally
      occurring and genetically generated mouse mutants and the transplantation of
      oligodendrocyte precursor cells (OPCs) following experimental  demyelination.
      However, aforementioned studies were exclusively carried out in rats and little
      is known about the in vivo behavior of transplanted murine OPCs. Therefore in the
      present study, we (i) established a model of ethidium bromide-induced
      demyelination of the caudal cerebellar peduncle  (CCP) in the adult mouse and
      (ii) studied the distribution and marker expression of the murine OPC line BO-1
      expressing the enhanced green fluorescent protein (eGFP) 10 and 17 days after
      stereotaxic implantation. Injection of ethidium bromide (0.025%) in the CCP
      resulted in a severe loss of  myelin, marked astrogliosis, and mild to moderate
      axonal alterations. Transplanted cells formed an invasive and liquorogenic
      metastasizing tumor, classified as murine giant cell glioblastoma. Transplanted
      BO-1 cells displayed substantially reduced CNPase expression as compared to their
      in  vitro phenotype, low levels of MBP and GFAP, prominent upregulation of NG2,
      PDGFRalpha, nuclear p53, and an unaltered expression of signal transducer and
      activator of transcription (STAT)-3. Summarized environmental signaling in the
      brain stem was not sufficient to trigger oligodendrocytic  differentiation of BO
      1 cells and seemed to block CNPase expression. Moreover, the lack of the
      remyelinating capacity was associated with tumor formation indicating that BO-1
      cells may serve as a versatile experimental model to study tumorigenesis of glial
      tumors.

PMID- 22420306
TI  - Linagliptin: a novel methylxanthin based approved dipeptidyl peptidase-4
      inhibitor.
AB  - Chemically, methylxanthine nucleus based Linagliptin (BI-1356, BI-1356-BS) is a
      dipeptidyl peptidase-IV inhibitor, which has been developed by Boehringer
      Ingelheim in association with Lilly for the treatment of Type-II Diabetes.
      Linagliptin was marketed by Lilly under the trade name Tradjenta and Trajenta.
      Linagliptin was approved as the once-daily dose by USFDA on 2 May 2011, for the
      treatment of Type-II Diabetes. Linagliptin 5mg once daily dose was approved based
      on a clinical trial program, which was conducted on approximately 4,000 adults
      with Type-II Diabetes. Linagliptin demonstrated statistically significant mean
      difference in HbA1c from placebo of up to 0.72 percent, when it was used
      monotherapically. In patients, who were not adequately controlled on metformin or
      metformin plus sulphonylurea, the addition of Linagliptin resulted in a
      statistically significant mean difference in HbA1c from placebo of -0.6 percent.
      Linagliptin was observed to produce significant reduction in fasting plasma
      glucose (FPG) compared to placebo, when used as a monotherapy in combination with
      metformin, sulfonylurea and/or pioglitazone. Linagliptin demonstrated significant
      reduction post-prandial glucose (PPG) levels in two hours as compared with
      placebo in monotherapy as well as in combination with metformin. In vitro assays
      also anticipated that Linagliptin is a potent DPPIV inhibitor as well as it
      exhibits good selectivity for DPP-IV as compared with other DPPs. The in-vivo
      studies also demonstrated same anticipation with respect to Linagliptin.
      Consequently, increasing the GLP-1 levels so far improved glucose tolerance in
      both healthy animals. X-ray crystallography anticipates that Linagliptin
      complexes with human DPPIV enzyme, e.g. butynyl substituent occupies the S1
      hydrophobic pocket of the enzyme; the aminopiperidine substituent in the xanthine
      scaffold occupies the S2 subsite and its primary amine interacts with the key
      amino acid residues, which involves in the recognition of peptide substrates. In
      the present review, we have tried to cover comparative study of DPPIV inhibitors,
      chemistry, physical properties, commercial synthesis, patent portfolio,
      crystalline polymorphic forms of Linagliptin and its receptor interaction,
      Pharmacophore rational, mechanism, clinical studies, preclinical, adverse effect,
      available formulations, dose regimen, co-therapy of Linagliptin, giving emphasis
      on the medicinal chemistry aspects.

PMID- 22420307
TI  - The role of cannabinoids in inflammatory modulation of allergic respiratory
      disorders, inflammatory pain and ischemic stroke.
AB  - This review is intended to offer updated information on the involvement of
      cannabinoids in the process of inflammation, focusing on immune/allergic
      reactions, inflammatory pain and neuroinflammation and discussing the
      interactions among endocannabinoid metabolism, prostanoids and nitric oxide. Two
      types of cannabinoid receptors, CB1 and CB2, which belong to the G protein
      coupled receptor family, have been identified and are targeted by numerous
      exogenous and endogenous ligands. The activation of CB2 receptors on mast cells
      has direct antiinflammatory effects, causing decreased release of pro
      inflammatory mediators by these cells. The activation of CB1 receptors on
      bronchial nerve endings has bronchodilator effects by acting on the airway smooth
      muscle and may be beneficial in airway hyperreactivity and asthma. Moreover,
      pharmacologic interference with endocannabinoid metabolism has been demonstrated
      to result in anti-nociceptive activity, mediated by CB1 and CB2 receptors, in
      animal models of inflammatory pain. The presence of endocannabinoid machinery in
      the central nervous system, together with high levels of CB1 expression, suggests
      that the endocannabinoid system is an important modulator of neuroinflammation
      and a possible drug target. In selected conditions, the activation of CB1
      receptors in cerebral blood vessels can have beneficial antiischemic effects.
      However, as endocannabinoids can also bind to vanilloid receptors, they may also
      mediate neurotoxic effects.

PMID- 22420308
TI  - Sodium dependent multivitamin transporter (SMVT): a potential target for drug
      delivery.
AB  - Sodium dependent multivitamin transporter (SMVT; product of the SLC5A6 gene) is
      an important transmembrane protein responsible for translocation of vitamins and
      other essential cofactors such as biotin, pantothenic acid and lipoic acid.
      Hydropathy plot (Kyte-Dolittle algorithm) revealed that human SMVT protein
      consists of 635 amino acids and 12 transmembrane domains with both amino and
      carboxyl termini oriented towards the cytoplasm. SMVT is expressed in various
      tissues such as placenta, intestine, brain, liver, lung, kidney, cornea, retina
      and heart. This transporter displays broad substrate specificity and excellent
      capacity for utilization in drug delivery. Drug absorption is often limited by
      the presence of physiological (epithelial tight junctions), biochemical (efflux
      transporters and enzymatic degradation) and chemical (size, lipophilicity,
      molecular weight, charge etc.) barriers. These barriers may cause many potential
      therapeutics to be dropped from the preliminary screening portfolio and
      subsequent entry into the market. Transporter targeted delivery has become a
      powerful approach to deliver drugs to target tissues because of the ability of
      the transporter to translocate the drug to intracellular organelles at a higher
      rate. This review highlights studies employing SMVT transporter as a target for
      drug delivery to improve bioavailability and investigate the feasibility of
      developing SMVT targeted drug delivery systems.

PMID- 22420309
TI  - Leukotriene c4 synthase: upcoming drug target for inflammation.
AB  - Leukotrienes are important mediators of pain and inflammation and they are
      produced in the arachidonic acid pathway via 5-lipoxygenase. They have been shown
      to have important roles in pyresis following antigen attack and in aspirin-
      intolerant asthma. They promote inflammation processes including eosinophil
      migration, increase in vascular permeability and bronchoconstriction. Hence,
      targeting the enzymes involved in the synthesis of these mediators can lead to
      the development of novel anti-inflammatory drugs. However, no drugs have yet been
      developed targeting leukotriene C4 synthase, a key enzyme leading to the
      synthesis of cysteinyl leukotrienes. The recent elucidation of its crystal
      structure now opens up the possibility of drugs against it. The inhibitors
      developed for this enzyme until now and the structural features responsible for
      their activity are discussed in this review. This understanding could lead to the
      design of new chemical entities.

PMID- 22420310
TI  - Right-first-time isocratic preparative liquid chromatography-mass spectrometry
      purification.
AB  - Preparative RP-LCMS is widely used to purify compounds from crude reaction
      mixtures in drug discovery today. Method development for preparative Liquid
      Chromatography-Mass Spectrometry (LCMS) consists of finding the right balance
      between speed and quality, often leading to the use of fast generic gradients (5
      95% organic mobile phase) to purify compounds of various structures and polarity,
      which can be sometimes detrimental to the purity of the isolated compound.
      Isocratic elution is the best method to obtain high purity, but it usually
      requires a long trial and error method development to find the right eluent
      composition. Therefore it is mostly used to purify large quantities of product
      using for instance stack injections, but not for routine purification of
      structurally diverse compounds. Herein, we describe an empirical method that
      allows "right-first-time" purifications with isocratic elution on preparative RP
      LCMS, permitting isolation of compounds in high purity and yield.

PMID- 22420311
TI  - Photoelectron spectroscopy of anilinide and acidity of aniline.
AB  - The photoelectron spectrum of the anilinide ion has been measured. The spectrum
      exhibits a vibrational progression of the CCC in-plane bending mode of the
      anilino radical in its electronic ground state. The observed fundamental
      frequency is 524 +/- 10 cm(-1). The electron affinity (EA) of the radical is
      determined to be 1.607 +/- 0.004 eV. The EA value is combined with the N-H bond
      dissociation energy of aniline in a negative ion thermochemical cycle to derive
      the deprotonation enthalpy of aniline at 0 K; Delta(acid)H(0)(PhHN-H) = 1535.4 +/
      0.7 kJ mol(-1). Temperature corrections are made to obtain the corresponding
      value at 298 K and the gas-phase acidity; Delta(acid)H(298)(PhHN-H) = 1540.8 +/-
      1.0 kJ mol(-1) and Delta(acid)G(298)(PhHN-H) = 1509.2 +/- 1.5 kJ mol(-1),
      respectively. The compatibility of this value in the acidity scale that is
      currently available is examined by utilizing the acidity of acetaldehyde as a
      reference.

PMID- 22420312
TI  - Nuclear-targeted drug delivery of TAT peptide-conjugated monodisperse mesoporous
      silica nanoparticles.
AB  - Most present nanodrug delivery systems have been developed to target cancer cells
      but rarely nuclei. However, nuclear-targeted drug delivery is expected to kill
      cancer cells more directly and efficiently. In this work, TAT peptide has been
      employed to conjugate onto mesoporous silica nanoparticles (MSNs-TAT) with high
      payload for nuclear-targeted drug delivery for the first time. Monodispersed MSNs
      TAT of varied particle sizes have been synthesized to investigate the effects of
      particle size and TAT conjugation on the nuclear membrane penetrability of MSNs.
      MSNs-TAT with a diameter of 50 nm or smaller can efficiently target the nucleus
      and deliver the active anticancer drug doxorubicin (DOX) into the targeted
      nucleus, killing these cancer cells with much enhanced efficiencies. This study
      may provide an effective strategy for the design and development of cell-nuclear
      targeted drug delivery.

PMID- 22420313
TI  - Community readiness for adopting a physical activity program for people with
      arthritis in West Virginia.
AB  - INTRODUCTION: The health benefits of physical activity are well established in
      older adults with arthritis. Despite these benefits, many older adults with
      arthritis are not active enough to maintain health; therefore, increasing
      physical activity in adults with arthritis is a public health priority. The
      purpose of this study was to use the Community Readiness Model to assess
      readiness for adopting a physical activity program for people with arthritis in 8
      counties in West Virginia. METHODS: During 2007 and 2008, we conducted a
      telephone survey among 94 key informants who could provide insight into their
      community's efforts to promote physical activity among older adults with
      arthritis. We matched survey scores with 1 of 9 stages of readiness, ranging from
      1 (no awareness) to 9 (high level of community ownership). RESULTS: The survey
      placed the counties in stage 3 (vague awareness), indicating recognition of the
      need for more physical activity programming; community efforts were not focused
      and leadership was minimal. The interviews suggested that culturally sensitive,
      well-promoted free or low-cost programs conducted by community volunteers may be
      keys to success in West Virginia. CONCLUSION: Information derived from our survey
      can be used to match intervention strategies for promoting physical activity
      among people with arthritis to communities in West Virginia according to their
      level of readiness.

PMID- 22420314
TI  - A summary of public access defibrillation laws, United States, 2010.
AB  - INTRODUCTION: On average, less than 8% of people who experience an out-of
      hospital cardiac arrest survive. However, death from sudden cardiac arrest is
      preventable if a bystander quickly retrieves and applies an automated external
      defibrillator (AED). Public access defibrillation (PAD) policies have been
      enacted to create programs that increase the public availability of these
      devices. The objective of this study was to describe each state's legal
      requirements for recommended PAD program elements. METHODS: We reviewed state
      laws and described the extent to which 13 PAD program elements are mandated in
      each state. RESULTS: No jurisdiction requires all 13 PAD program elements, 18%
      require at least 10 elements, and 31% require 3 or fewer elements. All
      jurisdictions provide some level of immunity to AED users, 60% require PAD
      maintenance, 59% require emergency medical service notification, 55% impose
      training requirements, and 41% require medical oversight. Few jurisdictions
      require a quality improvement process. CONCLUSION: PAD programs in many states
      are at risk of failure because critical elements such as maintenance, medical
      oversight, emergency medical service notification, and continuous quality
      improvement are not required. Policy makers should consider strengthening PAD
      policies by enacting laws that can reduce the time from collapse to shock, such
      as requiring the strategic placement of AEDs in high-risk locations or mandatory
      PAD registries that are coordinated with local EMS and dispatch centers. Further
      research is needed to identify the most effective PAD policies for increasing AED
      use by lay persons and improving survival rates.

PMID- 22420315
TI  - Gastric bypass surgeries in New Hampshire, 1996-2007.
AB  - INTRODUCTION: Obesity is a national epidemic. Gastric bypass surgery may be the
      only option that provides significant long-term weight loss for people who are
      morbidly obese (body mass index [BMI] >= 40 kg/m2) or for people who have a BMI
      of 35 or higher and have an obesity-related comorbidity. The objective of this
      study was to assess trends in gastric bypass surgery in New Hampshire. METHODS:
      Data from 1996 to 2007 from the New Hampshire Inpatient Hospital Discharge data
      set were analyzed. Records for patients with a gastric bypass surgery code were
      identified, and data on patients and hospitalizations were collected. A joinpoint
      regression model was used to analyze trends in surgery rates. Differences between
      patients and payer types were analyzed by using the Cochran-Mantel-Haenszel chi2
      test. RESULTS: The annual rate of gastric bypass surgery increased significantly
      from 3.3 to 22.4 per 100,000 adults between 1996 and 2007. The in-hospital death
      rate decreased significantly from 11% in 1996 to 1% in 2007. A greater proportion
      of women (78.1% during the study period) than men had this surgery. The average
      charge of a surgery decreased significantly from $44,484 in 1996 to $43,907 in
      2007; by 2007, total annual charges were $13.9 million. Since 1996, private or
      "other" payers have been charged for nearly 80% of the total discharges.
      CONCLUSION: The number of gastric bypass surgeries has increased in New
      Hampshire, and so have their cost. These increases may reflect a shortage in
      effective primary care and preventive measures to address the obesity epidemic.

PMID- 22420317
TI  - Dietary mustard seeds (Sinapis alba Linn) suppress 1,2-dimethylhydrazine-induced
      immuno-imbalance and colonic carcinogenesis in rats.
AB  - In a Wistar rat model, prolonged supplementation of mustard seed (MS) to the diet
      significantly ameliorates the induction of colorectal carcinomas by 1,2
      dimethylhydrazine (DMH). The expression of the splenocyte major
      histocompatibility complex class I (MHCI) was found significantly enhanced,
      whereas that of the major histocompatibility complex class II (MHCII) was
      significantly decreased. Compared to that of control animals, the proportion of
      spleenic B- and dendritic cells (DC) was amplified in the MS group. The
      expressions of MHCI, as well as that of MHCII, were increased in DC cells;
      whereas in B cells, MHCI expression was augmented but that of MHCII moderately
      decreased. The percentages of CD8+CD28+ and CD4+CD28+ cells were increased in the
      MS group, while the CD4+CD25+Foxp3+ subset was depressed. Plasma analysis showed
      that DMH-exposure induced amplified amounts of interleukin (IL)-4, IL-5, IL-10,
      and transforming growth factor-beta, whereas MS feeding counteracted this effect
      but enhanced IL-2, IL12p70, IL21, TNF-alpha, and interferon-gamma. In the SW480
      colon adenocarcinoma cell-line, the cytotoxicity of spleenic T-cells from MS-fed
      animals was significantly increased. In the DMH-exposed rats, the expression of
      perforin in the spleenic T-cells was dramatically decreased, whereas MS abolished
      this depression. In summary, dietary MS suppresses DMH-induced immuno-imbalance
      as well as colon carcinogenesis in rats.

PMID- 22420318
TI  - p53-induced uncoupling expression of aquaporin-4 and inwardly rectifying K+ 4.1
      channels in cytotoxic edema after subarachnoid hemorrhage.
AB  - AIMS: To investigate the mechanism behind cytotoxic edema formation following
      subarachnoid hemorrhage (SAH). METHODS: We explored the role of aquaporin-4
      (AQP4), inwardly rectifying K(+) 4.1 (Kir4.1) channels and their upstream
      orchestrators p53 and p38MAPK in this process. A p53 inhibitor, pifithrin-alpha
      (PFT-alpha) was administered intraperitoneally to rats undergoing SAH by
      endovascular perforation. Totally, 98 male SD rats were categorized into sham,
      SAH, SAH+ dimethyl sulfoxide (DMSO), SAH+ 0.2 or 2.0 mg/kg PFT-alpha groups. At
      24 h after SAH, MRI (diffusion-weighted imaging [DWI]), immunohistochemistry, and
      Western blot were used. RESULTS: MRI (DWI) showed a significant cytotoxic edema
      in the brain following SAH with PFT-alpha therapy reducing it.
      Immunohistochemistry and Western blot showed an increased level of p53,
      phosphorylated-p38MAPK and AQP4 and a reduced level of Kir4.1; all of which could
      be reversed following PFT-alpha treatment. Treble labeling staining revealed
      colocalization of p53 with phosphorylated-p38MAPK and unmatched expression of
      AQP4 and Kir4.1 within astrocyte cells. CONCLUSION: These results indicated p53
      mediates the formation of cytotoxic edema in the brain following SAH; an
      uncoupling expression of AQP4 and Kir4.1 on astrocytic end feet orchestrated by
      p38MAPK was partly responsible.

PMID- 22420316
TI  - The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral
      sclerosis spectrum.
AB  - There is increasing evidence that frontotemporal lobar degeneration (FTLD) and
      amyotrophic lateral sclerosis (ALS) represent a continuum of neurodegenerative
      diseases. FTLD is complicated by ALS in a significant proportion of patients, and
      neuropsychological studies have demonstrated frontotemporal dysfunction in up to
      50% of ALS patients. More recently, advances in neuropathology and molecular
      genetics have started to disclose the biological basis for the observed clinical
      concurrence. TDP-43 and FUS have been discovered as key pathological proteins in
      both FTLD and ALS. The most recent discovery of a pathological hexanucleotide
      repeat expansion in the gene C9orf72 as a frequent cause of both FTLD and ALS has
      eventually confirmed the association of these two at first sight distinct
      neurodegenerative diseases. Mutations in the TARDBP, FUS, and VCP genes had
      previously been associated with different phenotypes of the FTLD-ALS spectrum,
      although in these cases one end of the spectrum predominates. Whilst on the one
      hand providing evidence for overlap, these discoveries have also highlighted that
      FTLD and ALS are etiologically diverse. In this review, we review the recent
      advances that support the existence of an FTLD-ALS spectrum, with particular
      emphasis on the molecular genetic aspect.

PMID- 22420319
TI  - Transfusion-related Epstein-Barr virus infection among stem cell transplant
      recipients: a retrospective cohort study in children.
AB  - BACKGROUND: Blood safety warrants strict screening measures to minimize the risk
      of transmitting blood-borne pathogens. However, transfusion-transmitted
      infections for which testing is not currently performed continue to be a concern.
      Among these untested agents is Epstein-Barr virus (EBV) which, in the transplant
      setting, is associated with lymphoproliferative disease, a potentially fatal
      cancer. The aim of this study was to analyze the incidence of posttransplant EBV
      infection and its association with administration of blood products in children
      receiving a hematopoietic stem cell (HSC) graft. STUDY DESIGN AND METHODS: This
      retrospective cohort study sought to review charts of pediatric recipients of HSC
      grafts to collect information on the presence of EBV antibodies in the
      recipients' pretransplant sera and in HSC donor sera, incidence of posttransplant
      EBV infection, and patients' transfusion history. Cumulative incidence of
      posttransplant EBV infection was estimated by Kaplan-Meier methods according to
      pretransplant serology. The association between blood products and EBV infection
      was measured by Cox regression models. RESULTS: The pretransplant EBV
      seroprevalence was 77.9% for recipients and 61.8% for graft donors. Virtually,
      all recipients received blood products during the peritransplant period. Among
      seronegative recipients, the 30- and 60-day cumulative incidences of
      posttransplant EBV infection were 4.6 (95% confidence interval [CI], 1.2-17.3)
      and 13.4% (95% CI, 5.8%-29.4%), respectively. The 60-day cumulative incidence was
      8.3% (95% CI, 2.2%-29.4%) when restricting the analysis to seronegative
      recipients of cord blood grafts. Importantly, there was a clear positive trend
      associating EBV infection to transfusion volume. CONCLUSION: This study suggests
      an association between transfusions and posttransplant EBV infection in HSC
      transplant recipients.

PMID- 22420320
TI  - Lymphodepletion and homeostatic proliferation: implications for transplantation.
AB  - Control of the alloimmune response requires elimination and/or suppression of
      alloreactive immune cells. Lymphodepleting induction therapies are increasingly
      used to accomplish this goal, both as part of tolerance induction protocols or to
      reduce the requirements for maintenance immunosuppression in the peritransplant
      setting. However, it is well recognized that lymphopenia induces compensatory
      proliferation of immune cells, generally termed ''homeostatic proliferation,''
      which favors the emergence of memory T cells. Paradoxically therefore, the result
      may be a situation that favors graft rejection and/or makes tolerance difficult
      to achieve or sustain. Yet all depletion is not alike, particularly with respect
      to the timing of reconstitution and the types of cells that repopulate the host.
      Thus, to design more effective induction strategies it is important to understand
      the homeostatic mechanisms, which exist to maintain a balanced repertoire of
      naive and memory T and B cells in the periphery and how they respond to
      lymphodepletion. Here we will review the biology of homeostatic proliferation
      stimulated by lymphopenia, the effects of specific depleting agents on
      reconstitution of the T- and B-cell immune repertoire, drawing from both from
      animal models and human experience, and potential strategies to enhance
      allodepletion while minimizing the adverse effects of homeostatic proliferation.

PMID- 22420321
TI  - Predicting caregiver gains: a longitudinal study.
AB  - OBJECTIVES: The aim of this study was to examine if changes in motivations to
      care, familism, illness perceptions, caregiver tasks, coping, and social support
      were related to caregiver reported gains (subjective feelings of satisfaction and
      rewards as a result of the care role). DESIGN: A longitudinal design was employed
      whereby 123 caregivers completed a questionnaire at three time points: baseline,
      3 months, and 9 months from baseline. METHOD: Independent variables were
      converted into residual change scores (between time 1 and time 2) and their
      influence on caregiver gains at time 2 and time 3 was examined. RESULTS:
      Caregiver reported gains remained stable over time. Hierarchical regression
      analysis found that an increase in illness coherence was a strong predictor of
      caregiver gains at time 2, whereas predictors of time 3 gains included ethnicity,
      number of hours caregiving, and an increase in self-distraction and denial as
      coping methods. CONCLUSION: The study has implications for the development of
      time-specific interventions to increase caregiver gains and also for service
      development.

PMID- 22420323
TI  - Continuous time modelling with individually varying time intervals for
      oscillating and non-oscillating processes.
AB  - When designing longitudinal studies, researchers often aim at equal intervals. In
      practice, however, this goal is hardly ever met, with different time intervals
      between assessment waves and different time intervals between individuals being
      more the rule than the exception. One of the reasons for the introduction of
      continuous time models by means of structural equation modelling has been to deal
      with irregularly spaced assessment waves (e.g., Oud & Delsing, 2010). In the
      present paper we extend the approach to individually varying time intervals for
      oscillating and non-oscillating processes. In addition, we show not only that
      equal intervals are unnecessary but also that it can be advantageous to use
      unequal sampling intervals, in particular when the sampling rate is low. Two
      examples are provided to support our arguments. In the first example we compare a
      continuous time model of a bivariate coupled process with varying time intervals
      to a standard discrete time model to illustrate the importance of accounting for
      the exact time intervals. In the second example the effect of different sampling
      intervals on estimating a damped linear oscillator is investigated by means of a
      Monte Carlo simulation. We conclude that it is important to account for
      individually varying time intervals, and encourage researchers to conceive of
      longitudinal studies with different time intervals within and between individuals
      as an opportunity rather than a problem.

PMID- 22420324
TI  - Terra firma-forme dermatosis: another cause of reticulate pigmentation.

PMID- 22420322
TI  - The nonpeptide oxytocin receptor agonist WAY 267,464: receptor-binding profile,
      prosocial effects and distribution of c-Fos expression in adolescent rats.
AB  - Previous research suggests that the nonpeptide oxytocin receptor (OTR) agonist
      WAY 267,464 may only partly mimic the effects of oxytocin in rodents. The present
      study further explored these differences and related them to OTR and vasopressin
      1a receptor (V(1a) R) pharmacology and regional patterns of c-Fos expression.
      Binding data for WAY 267,464 and oxytocin were obtained by displacement binding
      assays on cellular membranes, while functional receptor data were generated by
      luciferase reporter assays. For behavioural testing, adolescent rats were tested
      in a social preference paradigm, the elevated plus-maze (EPM) and for locomotor
      activity changes following WAY 267,464 (10 and 100 mg/kg, i.p.) or oxytocin (0.1
      and 1 mg/kg, i.p.). The higher doses were also examined for their effects on
      regional c-Fos expression. Results showed that WAY 267,464 had higher affinity
      (K(i) ) at the V(1a) R than the OTR (113 versus 978 nm). However, it had no
      functional response at the V(1a) R and only a weak functional effect (EC(50) ) at
      the OTR (881 nm). This suggests WAY 267,464 is an OTR agonist with weak affinity
      and a possible V(1a) R antagonist. Oxytocin showed high binding at the OTR (1.0
      nm) and V(1a) R (503 nm), with a functional EC(50) of 9.0 and 59.7 nm,
      respectively, indicating it is a potent OTR agonist and full V(1a) R agonist. WAY
      267,464 (100 mg/kg), but not oxytocin, significantly increased the proportion of
      time spent with a live rat, over a dummy rat, in the social preference test.
      Neither compound affected EPM behaviour, whereas the higher doses of WAY 267,464
      and oxytocin suppressed locomotor activity. WAY 267,464 and oxytocin produced
      similar c-Fos expression in the paraventricular hypothalamic nucleus, central
      amygdala, lateral parabrachial nucleus and nucleus of the solitary tract,
      suggesting a commonality of action at the OTR with the differential doses
      employed. However, WAY 267,464 caused greater c-Fos expression in the medial
      amygdala and the supraoptic nucleus than oxytocin, and lesser effects in the
      locus coeruleus. Overall, our results confirm the differential effects of WAY
      267,464 and oxytocin and suggest that this may reflect contrasting actions of WAY
      267,464 and oxytocin at the V(1a) R. Antagonism of the V(1a) R by WAY 267,464
      could underlie some of the prosocial effects of this drug either through a direct
      action or through disinhibition of oxytocin circuitry that is subject to
      vasopressin inhibitory influences.

PMID- 22420325
TI  - The effects of age, isoflurane and sevoflurane on atracurium in lambs.
AB  - OBJECTIVE: To determine the effects of age, sevoflurane and isoflurane on
      atracurium-induced neuromuscular blockade in 3-16 week-old lambs. STUDY DESIGN:
      Prospective randomized experimental trial. ANIMALS: Twenty-six Scottish blackface
      ewe-lambs were anaesthetized for spinal surgery when either 3-6 (mean age 4.6
      weeks; n = 18) or 12-16 weeks (mean age 13.7 weeks; n = 15) of age; seven animals
      were anaesthetized at both ages. METHODS: After intramuscular injection of
      medetomidine (10 MUg kg(-1)) anaesthesia was induced in the younger lambs either
      with isoflurane or sevoflurane in oxygen delivered by mask, and in the older
      lambs with ketamine (4 mg kg(-1)), and midazolam (0.2 mg kg(-1) ) administered
      intravenously (IV). In both groups anaesthesia was maintained with fixed end
      tidal concentrations of either sevoflurane (2.8%) or isoflurane (1.8%) delivered
      in oxygen. Before surgery meloxicam (0.6 mg kg(-1)), morphine (0.5 mg kg(-1)) and
      ketamine (1 mg kg(-1) followed by 10 MUg kg(-1) minute(-1) ) were administered
      IV. The lungs were ventilated mechanically to maintain normocapnia. Neuromuscular
      block was achieved with a loading dose (LD) of atracurium (0.5 mg kg(-1) IV). The
      peroneal nerve was stimulated (train-of-four every 12 seconds). Evoked responses
      in the digital extensor muscles were evaluated by palpation and observation.
      Maintenance doses (MD) of atracurium (0.17 mg kg(-1) IV) were administered when
      the first twitch (T1) returned. The onset and duration of LD action (T1 absent)
      and the duration of MD were recorded. Data were analysed using Student's t test,
      Mann-Whitney U test, repeated-measures anova, Wilcoxon's matched pairs test or
      Pearson correlation coefficient as relevant (p < 0.05). RESULTS: Onset of LD
      action developed significantly (p < 0.05) more rapidly in isoflurane compared
      with sevoflurane-anaesthetized lambs (55 +/- 18 cf. 80 +/- 37 seconds). Duration
      of action of LDs and MDs was longer (p < 0.05) in lambs aged 12-16 than 3-6 weeks
      (33 +/- 5.4 cf. 25 +/- 6.4 and 26 +/- 4.2 cf. 18 +/- 5.5 minutes) but were
      independent of the anaesthetic used. CONCLUSIONS AND CLINICAL RELEVANCE: The
      effect of atracurium is age-dependent in lambs being prolonged in older animals.
      The onset of neuromuscular blockade is more rapid in isoflurane compared with
      sevoflurane-anaesthetized lambs.

PMID- 22420326
TI  - Executive functions and social skills in survivors of pediatric brain tumor.
AB  - Medical advances have resulted in increased survival rates for children with
      brain tumors. Consequently, issues related to survivorship have become more
      critical. The use of multimodal treatment, in particular cranial radiation
      therapy, has been associated with subsequent cognitive decline. Specifically,
      deficits in executive functions have been reported in survivors of various types
      of pediatric brain tumor. Survivors are left with difficulties, particularly in
      self-monitoring, initiation, inhibition, and planning, to name a few. Another
      domain in which survivors of pediatric brain tumor have been reported to show
      difficulty is that of social skills. Parents, teachers, and survivors themselves
      have reported decreased social functioning following treatment. Deficits in
      executive functions and social skills are likely interrelated in this population,
      as executive skills are needed to navigate various aspects of social interaction;
      however, this has yet to be studied empirically. Twenty-four survivors of
      pediatric brain tumor were assessed using a computerized task of executive
      functions, as well as paper-and-pencil measures of social skills and real-world
      executive skills. Social functioning was related to a specific aspect of
      executive functions, that is, the survivors' variability in response time, such
      that inconsistent responding was associated with better parent-reported and
      survivor-reported social skills, independent of intellectual abilities.
      Additionally, parent-reported real-world global executive abilities predicted
      parent-reported social skills. The implications of these findings for social
      skills interventions and future research are discussed.

PMID- 22420327
TI  - Cinacalcet: will it play a role in reducing cardiovascular events?
AB  - Secondary hyperparathyroidism is a common complication of chronic kidney disease
      and it is associated with high morbidity and mortality. It is characterized by
      high parathyroid hormone levels and bone turnover leading to bone pain, deformity
      and fragility. Furthermore, secondary hyperparathyroidism adversely affects the
      cardiovascular system and has been associated with cardiovascular calcification
      and cardiomyopathy. Cinacalcet, a type II calcimimetic, is an effective and well
      tolerated oral therapy for the management of secondary hyperparathyroidism. It is
      an allosteric activator of the calcium-sensing receptor enhancing sensitivity of
      parathyroid cells to extracellular calcium, which leads to inhibition of
      parathyroid hormone secretion. The calcium-sensing receptor expression in
      cardiomyocytes, endothelial cells and vascular smooth muscle cells raises the
      possibility that this receptor may be implicated in the pathophysiology of
      cardiovascular disease and constitute a potential therapeutic target. This
      article reviews the role of the calcimimetic agent cinacalcet in the prevention
      and progression of cardiovascular calcification and uremic cardiomyopathy in the
      chronic kidney disease setting.

PMID- 22420328
TI  - The REG1 anticoagulation system: a novel actively controlled factor IX inhibitor
      using RNA aptamer technology for treatment of acute coronary syndrome.
AB  - Antithrombotic agents including anticoagulants and antiplatelets are the
      cornerstone of treatment of acute coronary syndromes. Currently available
      anticoagulants have several important limitations including unpredictable
      pharmacodynamics, immunogenicity, and difficulty in reversibility. A potent
      anticoagulant that has predictable efficacy, is easily reversible should the
      clinical need arise, and reduces ischemic events without an increase in bleeding
      risk would overcome many of the current limitations. Inhibition of factor IX in
      the coagulation cascade has shown promise as a target for development of a novel
      anticoagulant with a favorable bleeding risk. Aptamers are small oligonucleotides
      that can be developed to inhibit specific protein targets with high affinity and
      used as active drugs. Because aptamers are made of oligonucleotide sequences,
      they provide the code for their own complement (reversal agent) that can be
      developed and used to inhibit their function. The REG1 anticoagulation system is
      a novel, aptamer-based, factor IXa inhibitor that is being developed for use in
      patients undergoing percutaneous coronary intervention and the treatment of acute
      coronary syndrome.

PMID- 22420329
TI  - Adding denture cleanser to microwave disinfection regimen to reduce the
      irradiation time and the exposure of dentures to high temperatures.
AB  - BACKGROUND: The microwave energy is an efficient disinfection method; however, it
      can generate high temperatures that can result in distortion of the dentures.
      OBJECTIVES: To evaluate whether the addition of an enzymatic cleanser to
      microwave disinfection regimen would disinfect dentures with shorter irradiation
      time. MATERIALS AND METHODS: Seven resin discs colonized with Candida albicans
      biofilm were placed on the palatal surface of sterile dentures to be randomly
      assigned to the following treatments: immersion in distilled water for 3 min with
      0 (DW), 1 (DW + M1), 2 (DW + M2), or 3 min (DW + M3) of microwave irradiation; or
      immersion in denture cleanser for 3 min with 0 (DC), 1 (DC + M1), 2 (DC + M2) or
      3 min (DC + M3) of irradiation. After the treatments, the viable cells were
      counted by a blinded examiner. The temperature was measured immediately after
      irradiation. The data were analyzed by ANOVA and Tukey post hoc tests (alpha =
      0.05). RESULTS: No viable cells were found after DC + M2, DC + M3, and DW + M3
      treatments, of which DC + M2 achieved the lowest temperature. No significant
      difference was found between the effectiveness of DW, DW + M1 and DC treatments
      (p > 0.05). CONCLUSION: Within the limits of this study, the association of a
      denture cleanser and microwave energy is efficient to disinfect dentures in lower
      irradiation time and temperature.

PMID- 22420330
TI  - Discovering opinion leaders for medical topics using news articles.
AB  - BACKGROUND: Rapid identification of subject experts for medical topics helps in
      improving the implementation of discoveries by speeding the time to market drugs
      and aiding in clinical trial recruitment, etc. Identifying such people who
      influence opinion through social network analysis is gaining prominence. In this
      work, we explore how to combine named entity recognition from unstructured news
      articles with social network analysis to discover opinion leaders for a given
      medical topic. METHODS: We employed a Conditional Random Field algorithm to
      extract three categories of entities from health-related new articles: Person,
      Organization and Location. We used the latter two to disambiguate polysemy and
      synonymy for the person names, used simple rules to identify the subject experts,
      and then applied social network analysis techniques to discover the opinion
      leaders among them based on their media presence. A network was created by
      linking each pair of subject experts who are mentioned together in an article.
      The social network analysis metrics (including centrality metrics such as
      Betweenness, Closeness, Degree and Eigenvector) are used for ranking the subject
      experts based on their power in information flow. RESULTS: We extracted 734,204
      person mentions from 147,528 news articles related to obesity from January 1,
      2007 through July 22, 2010. Of these, 147,879 mentions have been marked as
      subject experts. The F-score of extracting person names is 88.5%. More than 80%
      of the subject experts who rank among top 20 in at least one of the metrics could
      be considered as opinion leaders in obesity. CONCLUSION: The analysis of the
      network of subject experts with media presence revealed that an opinion leader
      might have fewer mentions in the news articles, but a high network centrality
      measure and vice-versa. Betweenness, Closeness and Degree centrality measures
      were shown to supplement frequency counts in the task of finding subject experts.
      Further, opinion leaders missed in scientific publication network analysis could
      be retrieved from news articles.

PMID- 22420331
TI  - Age-related changes in biochemical and hematologic variables in Borzoi and Beagle
      puppies from birth to 8 weeks.
AB  - BACKGROUND: Nonspecific signs of illness and availability of only limited
      information about expected biochemical and hematologic values in puppies make
      formulation of a differential diagnosis challenging for veterinarians.
      OBJECTIVES: The objectives of this prospective study were to describe age-related
      changes in biochemical and hematologic variables in Borzoi and Beagle puppies
      from birth to 8 weeks and to compare results with adult reference intervals
      (RIs). METHODS: Biochemical and hematologic analytes in blood collected in
      heparin and EDTA from 31 clinically healthy puppies (21 Beagle and 10 Borzoi
      dogs) were measured or calculated each week from birth to 8 weeks of age. RIs
      were calculated using the parametric robust method after Box-Cox transformation.
      RESULTS: There were no significant differences between values of puppies and
      adults for ALT activity, glucose concentration, MCHC, WBC count, and platelet
      count. Total protein concentration, RBC count, and HCT were lower and creatine
      kinase activity was higher in puppies of all ages compared with these variables
      in adults. Compared with adult RI, in puppies urea concentration was higher at
      birth and week 1, creatinine concentration was lower at weeks 1-5, ALP activity
      was higher at all weeks except for weeks 4 and 6, hemoglobin concentration was
      lower at weeks 1-8, MCV was higher at birth and week 1, and reticulocyte count
      was higher at all weeks except week 1. Statistically, mixed models accounted for
      evaluation of the same puppies each week and in most cases demonstrated an effect
      of age and sometimes breed. Some reference intervals should be used with caution
      owing to potential outliers. The 90% confidence intervals exceeded those
      recommended by the International Federation of Clinical Chemistry. CONCLUSIONS:
      Clinicians should be aware of temporal changes in biochemical and hematologic
      values for puppies during the first 2 months of life to avoid misinterpretation
      of results.

PMID- 22420333
TI  - Neutrophil CD64 is upregulated in patients with active adult-onset Still's
      disease.

PMID- 22420332
TI  - Extracellular ATP triggers proteolysis and cytosolic Ca2+ rise in Plasmodium
      berghei and Plasmodium yoelii malaria parasites.
AB  - BACKGROUND: Plasmodium has a complex cell biology and it is essential to dissect
      the cell-signalling pathways underlying its survival within the host. METHODS:
      Using the fluorescence resonance energy transfer (FRET) peptide substrate Abz
      AIKFFARQ-EDDnp and Fluo4/AM, the effects of extracellular ATP on triggering
      proteolysis and Ca2+ signalling in Plasmodium berghei and Plasmodium yoelii
      malaria parasites were investigated. RESULTS: The protease activity was blocked
      in the presence of the purinergic receptor blockers suramin (50 MUM) and PPADS
      (50 MUM) or the extracellular and intracellular calcium chelators EGTA (5 mM) and
      BAPTA/AM (25, 100, 200 and 500 MUM), respectively for P. yoelii and P. berghei.
      Addition of ATP (50, 70, 200 and 250 MUM) to isolated parasites previously loaded
      with Fluo4/AM in a Ca2+-containing medium led to an increase in cytosolic
      calcium. This rise was blocked by pre-incubating the parasites with either
      purinergic antagonists PPADS (50 MUM), TNP-ATP (50 MUM) or the purinergic
      blockers KN-62 (10 MUM) and Ip5I (10 MUM). Incubating P. berghei infected cells
      with KN-62 (200 MUM) resulted in a changed profile of merozoite surface protein 1
      (MSP1) processing as revealed by western blot assays. Moreover incubating P.
      berghei for 17 h with KN-62 (10 MUM) led to an increase in rings forms (82% +/-
      4, n = 11) and a decrease in trophozoite forms (18% +/- 4, n = 11). CONCLUSIONS:
      The data clearly show that purinergic signalling modulates P. berghei protease(s)
      activity and that MSP1 is one target in this pathway.

PMID- 22420334
TI  - A lack of association between elevated serum levels of S100B protein and
      autoimmunity in autistic children.
AB  - BACKGROUND: S100B is a calcium-binding protein that is produced primarily by
      astrocytes. Increased serum S100B protein levels reflect neurological damage.
      Autoimmunity may have a role in the pathogenesis of autism in some patients.
      Autoantibodies may cross the blood-brain barrier and combine with brain tissue
      antigens, forming immune complexes and resulting in neurological damage. We are
      the first to investigate the relationship between serum levels of S100B protein,
      a marker of neuronal damage, and antiribosomal P protein antibodies in autistic
      children. METHODS: Serum S100B protein and antiribosomal P antibodies were
      measured in 64 autistic children in comparison to 46 matched healthy children.
      RESULTS: Autistic children had significantly higher serum S100B protein levels
      than healthy controls (P < 0.001). Children with severe autism had significantly
      higher serum S100B protein than patients with mild to moderate autism (P = 0.01).
      Increased serum levels of antiribosomal P antibodies were found in 40.6% of
      autistic children. There were no significant correlations between serum levels of
      S100B protein and antiribosomal P antibodies (P = 0.29). CONCLUSIONS: S100B
      protein levels were elevated in autistic children and significantly correlated to
      autistic severity. This may indicate the presence of an underlying
      neuropathological condition in autistic patients. Antiribosomal P antibodies may
      not be a possible contributing factor to the elevated serum levels of S100B
      protein in some autistic children. However, further research is warranted to
      investigate the possible link between serum S100B protein levels and other
      autoantibodies, which are possible indicators of autoimmunity to central nervous
      system in autism.

PMID- 22420335
TI  - Interactions of DNA with a new platinum(IV) azide dipyridine complex activated by
      UVA and visible light: relationship to toxicity in tumor cells.
AB  - The Pt(IV) diazido complex trans,trans,trans-[Pt(N(3))(2)(OH)(2)(pyridine)(2)]
      (1) is unreactive in the dark but is cytotoxic when photoactivated by UVA and
      visible light. We have shown that 1 when photoactivated accumulates in tumor
      cells and binds strongly to nuclear DNA under conditions in which it is toxic to
      tumor cells. The nature of the DNA adducts, including conformational alterations,
      induced by photoactivated 1 are distinctly different from those produced in DNA
      by conventional cisplatin or transplatin. In addition, the observation that major
      DNA adducts of photoactivated 1 are able to efficiently stall RNA polymerase II
      more efficiently than cisplatin suggests that transcription inhibition may
      contribute to the cytotoxicity levels observed for photoactivated 1. Hence, DNA
      adducts of 1 could trigger a number of downstream cellular effects different from
      those triggered in cancer cells by DNA adducts of cisplatin. This might lead to
      the therapeutic effects that could radically improve chemotherapy by platinum
      complexes. The findings of the present work help to explain the different
      cytotoxic effects of photoactivated 1 and conventional cisplatin and thereby
      provide new insights into mechanisms associated with the antitumor effects of
      platinum complexes photoactivated by UVA and visible light.

PMID- 22420336
TI  - An artificial neural network model for predicting the subcellular localization of
      photosensitisers for photodynamic therapy of solid tumours.
AB  - Photodynamic therapy (PDT) is a promising modality for the treatment of tumours
      based on the combined action of a photosensitiser (PS), visible light and
      molecular oxygen, which generates a local oxidative damage that leads to cell
      death. The site where the primary photodynamic effect takes place depends on the
      subcellular localization of the PS and affects the mode of action and efficacy of
      PDT. It is therefore of prime interest to develop structure-subcellular
      localization prediction models for a PS from its molecular structure and
      physicochemical properties. Here we describe such a prediction method for the
      localization of macrocyclic PSs into cell organelles based on a wide set of
      physicochemical properties and processed through an artificial neural network
      (ANN). 128 2D-molecular descriptors related to lipophilicity/hydrophilicity,
      charge and structural features were calculated, then reduced to 76 by using
      Pearson's correlation coefficient, and finally to 5 using Guyon and Elisseeff's
      algorithm. The localization of 61 PSs was compiled from literature and
      distributed into 3 possible cell structures (mitochondria, lysosomes and "other
      organelles"). A non-linear ANN algorithm was used to process the information as a
      decision tree in order to solve PS-organelle assignment: first to identify PSs
      with mitochondrial and/or lysosomal localization from the rest, and to classify
      them in a second stage. This sequential ANN classification method has permitted
      to distinguish PSs located into two of the most important cell targets: lysosomes
      and mitochondria. The absence of false negatives in this assignation, combined
      with the rate of success in predicting PS localization in these organelles,
      permits the use of this ANN method to perform virtual screenings of drug
      candidates for PDT.

PMID- 22420337
TI  - Activity of epiisopiloturine against Schistosoma mansoni.
AB  - Schistosomiasis, caused by blood flukes of the genus Schistosoma, still imposes a
      considerable public health burden on large parts of the world. The control of
      this disease depends almost exclusively on the drug praziquantel, and there are
      no alternative drugs in sight. Natural compounds have recently attracted
      significant attention due to their relevance to parasitic infection and potential
      development into new therapeutic agents. Epiisopiloturine is an imidazole
      alkaloid isolated from the leaves of Pilocarpus microphyllus (Rutaceae), a native
      plant from Brazil. Here, we report the in vitro effect of this drug on the
      survival time of Schistosoma mansoni of different ages, such as 3 h old and 1, 3,
      5, and 7 days old schistosomula, 49-day-old adults, and on egg output by adult
      worms. Epiisopiloturine at a concentration of 300 MUg/mL caused the death of all
      schistosomula within 120 h. Extensive tegumental alterations and death were
      observed when adult schistosomes had been exposed to 150 MUg/mL of the
      epiisopiloturine. At the highest sub-lethal dose of alkaloid (100 MUg/mL), a 100%
      reduction in egg laying of paired adult worms was observed. Additionally,
      epiisopiloturine showed selective antischistosomal activity and exhibited no
      cytotoxicity to mammalian cells. This report provides the first evidence that
      epiisopiloturine is able to kill S. mansoni of different ages and inhibit worm
      egg laying.

PMID- 22420338
TI  - High-risk human papillomavirus-induced expression of endothelial and inducible
      nitric oxide synthase in human uterine cervix.
AB  - INTRODUCTION: Levels of nitric oxide metabolites are elevated in the cervical
      fluid of women with high-risk human papillomavirus (hrHPV). To elucidate the
      origin of this elevation we studied the cervical expression and localization of
      endothelial and inducible nitric oxide synthases (eNOS, iNOS) in women. MATERIAL
      AND METHODS: Expression of eNOS and iNOS was studied by Western blotting in the
      uterine cervixes of 86 women with (n = 41) and without (n = 45) hrHPV infection.
      The localization of eNOS and iNOS in cervical cells was studied by
      immunohistochemistry in 32 randomly selected women. RESULTS: Expression of eNOS
      and iNOS (in mean [95% CI] density units relative to actin) was higher in women
      with hrHPV versus those without (eNOS: 33.8 [22.5-45.1] versus 20.2 [6.1-34.3], P
      = 0.007; iNOS: 12.0 [7.1-16.9]) versus 5.6 [2.0-9.2], P = 0.003). Smoking reduced
      64% eNOS (P = 0.001) and 68% iNOS (P = 0.008) in women with hrHPV. Endothelial
      NOS was localized in the vascular endothelium, while iNOS was present in basal
      squamous epithelial cells. Low-grade histological lesions were accompanied by
      elevated expression of both eNOS and iNOS. CONCLUSIONS: High-risk HPV-associated
      elevation in cervical fluid nitric oxide metabolites results from both eNOS and
      iNOS stimulation. However, smoking seems to suppress this stimulation in hrHPV
      infected women.

PMID- 22420339
TI  - Application of the ADVIA cerebrospinal fluid assay to count residual red blood
      cells in blood components.
AB  - BACKGROUND AND OBJECTIVES: There is no automated, accurate assay for the
      enumeration of residual red blood cells (rRBCs) in non-RBC components for
      transfusion, despite the potential risk of allo-immunization when mismatched
      components are transfused. MATERIALS AND METHODS: The automated ADVIA 120
      cerebrospinal fluid (CSF) assay, which is approved to count RBCs and WBCs in CSF
      samples, was optimized and tested to measure rRBC in platelet concentrate (PC)
      and plasma components. RESULTS: Sample dilution, incubation time and reagent
      volume were optimized for use with non-RBC blood products. The assay was linear
      (R(2) = 0.99), even at low rRBCs counts. Intra- and inter-assay variation gave
      coefficients of variance (CV) between 2.2 and 9.4% and 2.6 and 14.9%,
      respectively, depending on rRBC levels. Good correlation (r = 0.995) was found
      between the automated assay and manual counting, which is considered the gold
      standard. Using the automated assay, the range of rRBCs (count/unit) in buffy
      coat platelet concentrate (PCs) was 27-5505 * 10(6) and in apheresis PCs was 1
      361 * 10(6). CONCLUSION: The ADVIA CSF assay is a sensitive, precise and accurate
      means to assess rRBC counts in non-RBC components.

PMID- 22420340
TI  - Fine mapping of a QTL for ear size on porcine chromosome 5 and identification of
      high mobility group AT-hook 2 (HMGA2) as a positional candidate gene.
AB  - BACKGROUND: Ear size and shape are distinct conformation characteristics of pig
      breeds. Previously, we identified a significant quantitative trait locus (QTL)
      influencing ear surface on pig chromosome 5 in a White Duroc*Erhualian F2
      resource population. This QTL explained more than 17% of the phenotypic variance.
      METHODS: Four new markers on pig chromosome 5 were genotyped across this F2
      population. RT-PCR was performed to obtain expression profiles of different
      candidate genes in ear tissue. Standard association test, marker-assisted
      association test and F-drop test were applied to determine the effects of single
      nucleotide polymorphisms (SNP) on ear size. Three synthetic commercial lines were
      also used for the association test. RESULTS: We refined the QTL to an 8.7-cM
      interval and identified three positional candidate genes i.e. HMGA2, SOX5 and
      PTHLH that are expressed in ear tissue. Seven SNP within these three candidate
      genes were selected and genotyped in the F2 population. Of the seven SNP, HMGA2
      SNP (JF748727: g.2836 A>G) showed the strongest association with ear size in the
      standard association test and marker-assisted association test. With the F-drop
      test, F value decreased by more than 97% only when the genotypes of HMGA2 g.2836
      A>G were included as a fixed effect. Furthermore, the significant association
      between g.2836 A>G and ear size was also demonstrated in the synthetic commercial
      Sutai pig line. The haplotype-based association test showed that the phenotypic
      variance explained by HMGA2 was similar to that explained by the QTL and at a
      much higher level than by SOX5. More interestingly, HMGA2 is also located within
      the dog orthologous chromosome region, which has been shown to be associated with
      ear type and size. CONCLUSIONS: HMGA2 was the closest gene with a potential
      functional effect to the QTL or marker for ear size on chromosome 5. This study
      will contribute to identify the causative gene and mutation underlying this QTL.

PMID- 22420342
TI  - Developmental pattern of digit span in Spanish population.
AB  - This study examined in a Spanish population the developmental pattern of digit
      span, as an index of one of the components of Baddeley's working memory--the
      phonological loop. A verbal digit span was administered to 570 participants
      ranging from 5 to 17 years old. The results indicated that the digit memory span
      increases until age 17 as opposed to Anglo-Saxon data--where it is established
      that this span reaches a peak by age 15. Additionally, these results were
      compared to the performance in the same task of healthy elderly, Alzheimer
      disease patients, and Frontotemporal dementia patients, examined in a previous
      study. The analysis shows that the phonological loop is affected by age and not
      so much by dementias.

PMID- 22420341
TI  - Photoperiodic changes in endocannabinoid levels and energetic responses to
      altered signalling at CB1 receptors in Siberian hamsters.
AB  - Siberian hamsters (Phodopus sungorus) adapt to seasonal environmental conditions
      with marked changes in body mass, primarily in the form of adiposity. Winter-like
      conditions (e.g. short days) are sufficient to decrease body mass by
      approximately 30% in part via reductions in food intake. The neuroendocrine
      mechanisms responsible for these changes are not well understood, and homeostatic
      orexigenic/anorexigenic systems of the hypothalamus provide little explanation.
      We investigated the potential role of endocannabinoids, which are known
      modulators of appetite and metabolism, in mediating seasonal changes in energy
      balance. Specifically, we housed hamsters in long or short days for 0, 3, or 9
      weeks and measured endocannabinoid levels in the hypothalamus, brainstem, liver
      and retroperitoneal white adipose tissue (RWAT). An additional group of males
      housed in short days for 25 weeks were also compared with long-day controls.
      Following 9 weeks in short days, levels of the endocannabinoid 2
      arachidonoylglycerol (2-AG) were significantly elevated in RWAT and reduced in
      brainstem, although they returned to long-day levels by week 25 in short-day
      males that had cycled back to summer-like energy balance. Endocannabinoid levels
      in these tissues correlated significantly with adiposity and change in body mass.
      No photoperiodic changes were observed in the hypothalamus or liver; however, sex
      differences in 2-AG levels were found in the liver (males > females). We further
      tested the effects of CB(1) receptor signalling on ingestive behaviour. Five
      daily injections of CB(1) antagonist SR141716 significantly reduced food intake
      and body mass but not food hoarding. Although the CB(1) agonist arachidonyl-2
      chloroethylamide did not appreciably affect either ingestive behaviour, body mass
      was significantly elevated following 2 days of injections. Taken altogether,
      these findings demonstrate that endocannabinoid levels vary with sex and
      photoperiod in a site-specific manner, and that altered signalling at CB(1)
      receptors affects energy balance in Siberian hamsters.

PMID- 22420343
TI  - [Is dyslexia a visual perceptive disorder? New empirical data].
AB  - Several studies have shown that a phonological deficit is the origin of
      developmental dyslexia, because dyslexics have important difficulties in mapping
      orthographic to phonological codes. However, visual criteria are still used for
      the diagnosis of dyslexia and to develop methods of intervention. This study
      attempts to determine whether there are visual problems in dyslexic children. To
      this aim, dyslexic children and children without reading difficulties, matched by
      chronological age, participated in two experiments. One study was based on the
      Reversal test and the other was a visual decision task in which participants had
      to decide whether two letters were the same or different. There were 40 pairs of
      letters, to measure reaction times and mistakes. The results showed that
      dyslexics had similar performance to controls in the detection of different
      visual stimuli. Developmental dyslexics do not appear to have visual perceptual
      problems, but a particular difficulty to retrieve the phonological code of
      graphemes.

PMID- 22420344
TI  - [Assimilation processes in the late stages of phonological development].
AB  - This article reports a research on late phonological assimilation processes in
      child language in order to determine the possible stages in their evolution and
      the variations in relative frequency as a function of directionality (progressive
      vs. regressive), distance (contiguous vs. non-contiguous), and type of phonemes
      involved in assimilations (consonants vs. vowels). The corpus analyzed was
      collected from 240 children ranging in age between three and six years old. The
      speech samples were obtained in naturalistic settings of spontaneous conversation
      with the researchers, and were transcribed and analyzed with the tools provided
      by the CHILDES Project. Results describe a profile with three stages, reflecting
      the general dynamics of phonological development. Around the age of four, a
      general reorganization of the phonological system takes place, and the least
      frequent assimilation processes (progressive, contiguous and intervocalic) tend
      to disappear earlier. The most frequent assimilation processes (regressive, non
      contiguous and inter-consonant) tend to persist as processing errors in the
      transition to adult speech. These findings show the functional complexity of late
      assimilation processes, as well as the need for taking it into account when
      planning clinical intervention.

PMID- 22420345
TI  - [Is an optimistic memory less easily influenced by negative than by positive
      emotions?].
AB  - This work examines whether a positive personality trait, such as optimism, can
      reduce bias in differential words recalled after inducing a certain emotion.
      After showing a list of words with various emotional valences to a group of 59
      subjects, a specific emotional state was induced. Subsequently, the subjects were
      asked to recall the list of words. The results obtained indicated that less
      optimistic subjects had a tendency to recall and recognize a greater number of
      negative words when in a negative emotional condition. Statistical significance
      was reached in the female group's negative word recognition when experiencing
      negative emotion.

PMID- 22420346
TI  - [The learning and motor development transfer process].
AB  - The aim of this study is to analyze the transference process in motor skill
      learning. For this purpose, 320 boys and girls, with ages ranging from 3 to 12
      years (M= 7.61; SD= 2.61), took part in nine object movement reception drills in
      which the following variables were cross-examined: the presence-absence of
      displacement (static or in motion), the corporal segments utilized (hands or
      arms), the movement direction (right or left), and the moving object (volleyball
      or tennis ball). The results indicate that what is being transferred is the
      common factor among them, the ocular-kinesthetic regulating system, which is
      constructed according to a generalized motor program and a predictive strategy of
      continuous control. The way that individuals group by levels of skill that
      represent the developmental levels of the aforementioned regulating system can
      also be observed. Lastly, the results are discussed, and strategies to improve
      the learning process in sports and physical education are provided.

PMID- 22420347
TI  - Sexual behavior in Spanish adolescents of divorced parents.
AB  - Marital breakup has been associated with numerous behavioral problems in
      children, such as sexual risk behaviors. This research is the first to examine
      sexual behaviors of Spanish adolescents related to whether their parents were
      married or divorced. Participants were 342 boys and girls aged between 14 and 18
      years. The sample provided confidential information about their sexual behavior
      and birth control methods. Significant differences were only found in percentages
      of adolescents who had engaged in mutual masturbation, intercourse, or oral sex,
      and who had practiced these sexual relations in the last six months, in both
      cases, they were higher when the parents had broken their marital relationship.
      Regarding adolescents of divorced parents, engaging in intercourse is more likely
      in older teenagers who live with a stepparent. Moreover, older adolescents who
      were younger when parents divorced and who live in a reconstituted family, have
      more sexual partners. These and other findings are discussed.

PMID- 22420348
TI  - [Evaluation of the effectiveness of a prison-based drug treatment].
AB  - The present study evaluated the effectiveness of a drug-free unit (DFU) in
      reducing the use of substances by incarcerated adult offenders, and to analyze
      changes in the addiction severity index, motivation, and personality caused by
      the program. This is an external evaluation, with an ex post facto design with
      repeated measures. Eighty-seven prisoners from the DFU were evaluated during the
      first year of residence in the program. Most are young men, polydrug addicts and
      mainly serving sentences for public health crimes and property offenses. There is
      need of psychiatric treatment at the baseline, with 85% comorbid personality
      disorders. Motivation for treatment is low, and remains stable over 12 month's
      duration of the study. The DFU was found to have a significant effect in reducing
      the use of drugs by offenders and to improve the drug and family composite
      scores, also reducing scores on personality scales. However, it fails to change
      medical and psychiatric scores, so that the need for intervention in these areas
      is underscored.

PMID- 22420349
TI  - Life review therapy using autobiographical retrieval practice for older adults
      with clinical depression.
AB  - The aim of this experiment was to examine the efficacy of life review based on
      autobiographical retrieval practice for treating depression in older adults.
      Thirty-seven clinically depressed older adults aged 64-83, who were also
      receiving pharmacological treatment, were randomly assigned to life review
      therapy or to a placebo condition with supportive therapy. Results indicated
      decreased depression for both conditions, with no significant differences between
      the two therapies. There was some indication of greater gain in production of
      specific memories among those in life review therapy. Patients who produced
      higher numbers of specific memories decreased their depression scores at a faster
      rate.

PMID- 22420350
TI  - [Avoidance coping style and the risk of developing an eating disorder in
      adolescents].
AB  - The first aim of this study was to analyse the relationship between coping styles
      and strategies in Spanish adolescents of both genders, with high and low eating
      disorder risk. Secondly, this study aims to examine the relation of coping styles
      and coping strategies with eating disorder risk. The sample comprised 2142
      adolescents (1.130 girls and 1.012 boys), mean age 13,96 years (SD= 1.34). They
      completed the Adolescent Coping Scale (ACS) and the Eating Attitude Test (EAT
      40). The results showed high use of intropunitive avoidance coping in both female
      and male adolescents with high EAT-40 scores. The regression analysis indicated
      that, in both girls and boys, the intropunitive avoidance and the tension
      reduction coping strategy explained a high percentage of variance of eating
      disorder risk. The results of this study have implications for the prevention of
      these behaviours in adolescents, because people with a high risk of developing an
      eating disorder present a maladaptive coping style before the onset of the eating
      disorder.

PMID- 22420351
TI  - Tolerance towards dating violence in Spanish adolescents.
AB  - The study of intimate partner violence among adolescent and young couples in
      Spain remains unattended, although such abuses are well known and more frequent
      than in adulthood. The aim of this study is, on the one hand, to provide
      epidemiological information on dating relationships, and on the other hand, to
      identify attitudes towards violence. 2205 women enrolled in schools in diverse
      provinces of Spain, participated in the study. Average age was near 19 years (SD=
      2.25). The Dating Violence Questionnaire (DVQ, in Spanish, CUVINO), a
      questionnaire that assesses both frequency and distress associated with violent
      behavior, was used. The DVQ allowed differentiating between groups of women self
      labeled as abused and not abused on the basis of the frequency of sustained
      violence, although the levels of distress in the face of violence were
      statistically similar in both groups. Implications for future research and
      prevention programs are discussed.

PMID- 22420352
TI  - [Terrorists and victims. Infrahumanization of Moroccans after 11-M].
AB  - Infrahumanization studies have verified that most people attribute more secondary
      emotions to the ingroup than to the outgroup. However, these results may vary
      with changing contexts. The main objective of this study was to investigate the
      infrahumanization of Moroccans, depending on the context, after the 11-M attacks
      and seven years later. For this purpose, variations that occur in the allocation
      of essential human qualities--secondary emotions--were analyzed by activating
      images of outgroup members in two opposite contexts: Guilty of the terrorist
      attack or its victim. The results show that the infrahumanization of the
      Moroccans in the perpetrator context does not change significantly with regard to
      the control group. However, infrahumanization does not take place when Moroccans
      are associated with a victim context, though only immediately after the terrorist
      attack, because seven years later, this effect disappears.

PMID- 22420353
TI  - [Measurement of Affect Regulation Styles (MARS) expanded].
AB  - An expanded Spanish version of the Measure of Affect Regulation Styles (MARS),
      was applied to episodes of anger and sadness, in a sample of 355 graduate
      students from Chile, Spain, and Mexico. The study examines the association
      between affective regulation, adaptation to episodes and dispositional coping and
      emotional regulation, and psychological well-being. With regard to perceived
      improvement of adaptive goals, the following adaptive affect regulation
      strategies were confirmed: Instrumental coping, seeking social support, positive
      reappraisal, distraction, rumination, self-comfort, self-control, and emotional
      expression were functional; whereas inhibition and suppression were
      dysfunctional. Adaptive strategies were positively associated with psychological
      well-being, reappraisal and humor as a coping strategy. Negative associations
      were found between adaptive strategies and suppression and alexithymia.
      Maladaptive strategies show the opposite profile. Confrontation, instrumental
      coping, social support as well as social isolation were more frequently found in
      anger, an approach emotion.

PMID- 22420354
TI  - [Influence of perceived social support and functioning on the quality of life of
      patients with schizophrenia and their caregivers].
AB  - Perception of social support and functioning of patients with schizophrenia and
      their primary caregivers and its relationship to quality of life are described.
      Forty-five patients and their 45 relatives, treated at the Mental Health Services
      in Arica, Chile, participated. Both patients and caregivers in the study have a
      poor perception of social support with regard to extra-family people, as well as
      a low social integration. However, patients showed adequate capacity to function
      within their immediate family. Unlike what was found in developed countries,
      these patients showed moderate levels of quality of life, with a strong
      relationship with perceptions of the social support they receive from family and
      significant others and the ability to establish and maintain social contacts.
      Quality of life of primary caregivers is linked to patients' ability to establish
      and maintain social contacts within the family group, as in other social
      instances, such as keeping a job. The results of the study suggest the need to
      consider the design and application of programs of support for these patients and
      their caregivers, with the central aim of the social functioning of the above
      mentioned patients and their familiar and community integration.

PMID- 22420355
TI  - A study of physicians' intention to quit: the role of burnout, commitment and
      difficult doctor-patient interactions.
AB  - Research on burnout and turnover intentions offers some inconsistent findings
      about the effects of commitment. In addition, a factor which is insufficiently
      studied in the turnover field is the relationship with the recipient of
      physicians' work, that is, the patient. This study contributes to the research
      literature by examining how the moderating effect of commitment depends on
      difficult doctor-patient relations. A total of 480 physicians, representative of
      Madrid, completed the survey. According to the interaction effects and the three
      way interaction analyses, the results support the argument that differences in
      commitment lead to differences in the way physicians perceive job, interpersonal,
      and chronic stress. These results add a new approach to the general assumption
      that commitment has a unilateral negative effect, and difficult patients have a
      positive effect on turnover intentions, suggesting an integrated perspective,
      rather than a diametrical one, that allows us comprehend the complexity of 
      physicians' turnover intentions.

PMID- 22420356
TI  - [Burnout and job satisfaction among nursing professionals].
AB  - The purpose of this study was to examine the relationship between burnout and job
      satisfaction among nursing professionals. The sample consisted of 316 staff
      nurses. The study was longitudinal, and not randomized. The gap between Time 1
      (T1) and Time 2 (T2) was one year. Hierarchical regression analysis showed
      empirical evidence of the significant and negative effect of burnout (i.e.,
      Emotional exhaustion and Depersonalization dimensions) at T1 on job satisfaction
      in T2. Significant results were also obtained that showed the influence of job
      satisfaction at T1 on burnout at T2 (i.e., Depersonalization dimension). The
      study concludes that there is a bidirectional and longitudinal relationship
      between burnout and job satisfaction. However, longitudinal effects of burnout at
      T1 on job satisfaction on T2 (i.e., burnout as antecedent of job satisfaction)
      are stronger than vice-versa (i.e., job satisfaction as antecedent of burnout).

PMID- 22420357
TI  - [Child-to-parent violence and its association with exposure to marital violence
      and parent-to-child violence].
AB  - The aims of this study were: (a) to examine the relationships between the
      exposure to different types of family violence (intraparental violence and parent
      to-child aggression) and the perpetration of child-to-parent violence (CPV); (b)
      to analyze sex differences in the relationships specified. The sample comprised
      1681 Spanish university students who reported the exposure to different types of
      family violence during their childhood. Both psychological and physical family
      violence were analyzed separately. Results showed that both witnessing marital
      psychological violence and parent-to-child psychological aggression are related
      to CPV. Furthermore, psychological and physical parent-to-child aggression as
      well as witnessing physical aggression between parents was associated with
      physical CPV. Multigroup analyses showed that the relationships among variables
      were not significantly different as a function of sex. This finding suggests that
      the relation between exposure to family violence and CPV is similar for men and
      women.

PMID- 22420359
TI  - [Prediction of mathematics achievement: effect of personal, socioeducational and
      contextual variables].
AB  - Based upon the self-regulated learning theoretical framework this study examined
      to what extent students' Math school achievement (fifth to ninth graders from
      compulsory education) can be explained by different cognitive-motivational,
      social, educational, and contextual variables. A sample of 571 students (10 to 15
      year old) enrolled in the study. Findings suggest that Math achievement can be
      predicted by self-efficacy in Math, school success and self-regulated learning
      and that these same variables can be explained by other motivational (ej.,
      achievement goals) and contextual variables (school disruption) stressing this
      way the main importance of self-regulated learning processes and the role context
      can play in the promotion of school success. The educational implications of the
      results to the school levels taken are also discussed in the present paper.

PMID- 22420358
TI  - [Parenting and children's aggression: are there differences in the influence of
      the father and the mother?].
AB  - Child rearing provides messages and rules that mediate the children's
      personality. These messages have a positive or negative influence on their
      behaviour. The objective of this empirical study was to analyse the relationship
      between physical and verbal aggression of sons and daughters and parenting style
      practiced by the father and the mother. The sample consisted of 2,788 students,
      aged 10 to 15 years, studying either the third cycle of Primary Education (44%)
      or the first cycle of Secondary Education (56%). Of them, 1,412 were boys (50.6%)
      and 1,375 were girls (49.3%). The results show that children's aggressiveness is
      more related to factors associated with the mother's parenting. In the case of
      daughters, the influence of parenting factors are caused by both parents (father
      and mother).

PMID- 22420360
TI  - Reduction of inflammatory pain in female rats after NR2B NMDA cortical
      antagonism.
AB  - Studies have shown that N-methyl-D-aspartate (NMDA) receptors play a critical
      role in pain processing at different levels of the central nervous system. In
      this study, we used female adult Wistar rats to examine the effects of
      antagonizing the NR2B subunit of the NMDA receptor in phasic and tonic pain
      processes. All the rats underwent stereotaxic surgery for cortical cannula
      implantation and after at least one week of recovery, rats performed behavioral
      tests. For evaluating the effects of drugs on motor coordination rats were tested
      in the rotarod apparatus. Moreover, rats were evaluated in the paw withdrawal
      latency (PWL) to a noxious thermal stimulus. Furthermore, rats were tested in the
      formalin-pain test. Rats that received the NR2B antagonist Ro 25-6981 before and
      after formalin injection showed significantly reduced pain responses in the
      formalin test, as compared with female control rats (p<0.05). In contrast, no
      differences among groups were found in the phasic pain test (Hargreaves) and the
      rotarod test. Taken together, these results suggest that cortical antagonism of
      the NR2B subunit of NMDA receptors is able to reduce inflammatory pain levels not
      only before, but after the formalin injection in females at different phases of
      the estrous cycle.

PMID- 22420361
TI  - [Factor analysis of ipsative data: a simulation study].
AB  - This paper introduces a summary on how to proceed to conduct a factor analysis
      when the input data are ipsative. The classical factor analysis procedures cannot
      be used because the covariance matrix is singular. Additionally, previous
      research on the optimal conditions to conduct factor analysis for ipsatized data
      is reviewed, and the results of a simulation study are presented. The study
      includes conditions of sample size, model complexity, and model specification
      (correct vs. incorrect). The results suggest that researchers should be careful
      when factor analyzing ipsatized data, particularly if they suspect that the model
      is incorrectly specified and includes a smaller number of factors.

PMID- 22420362
TI  - The impact of social desirability on psychometric measures of aggression.
AB  - Although many studies have focused on the effects of social desirability in
      personality measures, few have analysed its effects on such highly undesirable
      behaviour as aggressiveness. The present study analyzes the impact of social
      desirability on measures of direct and indirect aggression and on the
      relationships between both kinds of aggression with impulsivity, using a method
      that enables the content factors of the measures to be isolated from social
      desirability. Results showed that aggression measures are highly affected by
      social desirability and that the relationships between the two forms of
      aggression and impulsivity are due to the content measured by the tests and not
      to a common social desirability factor.

PMID- 22420363
TI  - [Evaluation of the factorial and metric equivalence of the Sexual Assertiveness
      Scale (SAS) by sex].
AB  - Sexual assertiveness refers to the ability to initiate sexual activity, refuse
      unwanted sexual activity, and use contraceptive methods to avoid sexually
      transmitted diseases, developing healthy sexual behaviors. The Sexual
      Assertiveness Scale (SAS) assesses these three dimensions. The purpose of this
      study is to evaluate, using structural equation modeling and differential item
      functioning, the equivalence of the scale between men and women. Standard scores
      are also provided. A total of 4,034 participants from 21 Spanish provinces took
      part in the study. Quota sampling method was used. Results indicate a strict
      equivalent dimensionality of the Sexual Assertiveness Scale across sexes. One
      item was flagged by differential item functioning, although it does not affect
      the scale. Therefore, there is no significant bias in the scale when comparing
      across sexes. Standard scores show similar Initiation assertiveness scores for
      men and women, and higher scores on Refusal and Sexually Transmitted Disease
      Prevention for women. This scale can be used on men and women with sufficient
      psychometric guarantees.

PMID- 22420364
TI  - [Scale of organizational learning in schools. Organizational learning is a key
      element for the development of organizations].
AB  - Organizational learning is a key element for the development of organizations.
      School organizations are not exempt from this challenge and they currently face a
      highly dynamic and demanding context of education policies that emphasize the
      school's ability to learn. Thus, research on organizational learning in
      educational contexts requires valid instruments that are sensitive to the
      specifics of schools as organizations. In this study, we adapted and validated a
      scale of organizational learning in a sample of 119 Chilean municipal schools (N=
      1,545). The results suggest a structural model made up of three factors: culture
      of learning, strategic clarity, and group learning. These factors predicted
      dimensions of educational achievement, as measured through the National
      Assessment System of Educational Achievement (SNED). Results are discussed in
      view of the literature on school improvement.

PMID- 22420365
TI  - Validation study of the Questionnaire on School Maladjustment Problems (QSMP).
AB  - The aim of this study was to analyze the exploratory and confirmatory structure,
      as well as other psychometric properties, of the Cuestionario de Problemas de
      Convivencia Escolar (CPCE; in Spanish, the Questionnaire on School Maladjustment
      Problems [QSMP]), using a sample of Spanish adolescents. The instrument was
      administered to 60 secondary education teachers (53.4% females and 46.6% males)
      between the ages of 28 and 54 years (M= 41.2, SD= 11.5), who evaluated a total of
      857 adolescent students. The first-order exploratory factor analysis identified 7
      factors, explaining a total variance of 62%. A second-order factor analysis
      yielded three dimensions that explain 84% of the variance. A confirmatory factor
      analysis was subsequently performed in order to reduce the number of factors
      obtained in the exploratory analysis as well as the number of items. Lastly, we
      present the results of reliability, internal consistency, and validity indices.
      These results and their implications for future research and for the practice of
      educational guidance and intervention are discussed in the conclusions.

PMID- 22420366
TI  - [Validation of the Spanish version of the Frankfurt Emotion Work Scales].
AB  - This study presents the validity and reliability analysis of a questionnaire that
      assesses emotion work in the service sector. Emotion work is a term introduced by
      Hochschild (1983) and it refers to the expression of organizationally desirable
      emotions to influence the interactions with clients at work. The results show a 6
      factor structure: Requirement to display Positive, Negative and Neutral Emotions,
      Sensitivity Requirements, Interaction Control and Emotional Dissonance. The
      analysis of the sub-scale scores reveals that the most frequently expressed
      emotions are positive, whereas negative emotions are expressed less frequently.

PMID- 22420368
TI  - Validation of a disease-specific questionnaire for measuring parent-reported
      health-related quality of life in children with allergies.
AB  - PURPOSE: To evaluate the properties and suitability of a disease-specific
      questionnaire to assess parent-reported health-related quality of life (HRQL) of
      children and parents of children suffering from food hypersensitivity (FHS) or
      allergy to furred pets (AFP). METHODS: The parents of 202 children with FHS and
      of 131 children with AFP filled in questionnaires comprising the CHQ-PF28 and the
      Food-Pet-Allergy in Children (FPAC) Questionnaire. Psychometric properties of the
      FPAC questionnaire were evaluated separately for FHS and AFP. RESULTS: Analyses
      resulted in five proposed scales: Limitations of Family/Child Activities (I),
      Parents' Distress (II), Child's Emotions (III), Child in School (IV) and Family
      Conflicts (V). Convergent/discriminant validity for scales I, II and III of both
      questionnaires was high; for scale IV it was moderate. All five FHS and four AFP
      scales were able to distinguish significantly between children with and without
      clinical allergy symptoms (known-group validity). Internal consistency
      reliability was good for scales I, II and III, but poor for scale IV. CONCLUSION:
      Three valid scales were determined for both FHS and AFP (Limitations of
      Family/Child Activities, Parents' Distress and Child's Emotions) and can be used
      in clinical research.

PMID- 22420367
TI  - The spleen is the major source of antidonor antibody-secreting cells in murine
      heart allograft recipients.
AB  - Antibody-mediated allograft rejection is an increasingly recognized problem in
      clinical transplantation. However, the primary location of donor-specific
      alloantibody (DSA)-producing cells after transplantation have not been
      identified. The purpose of this study was to test the contribution of
      allospecific antibody-secreting cells (ASCs) from different anatomical
      compartments in a mouse transplantation model. Fully MHC-mismatched heart
      allografts were transplanted into three groups of recipients: nonsensitized wild
      type, alloantigen-sensitized wild-type and CCR5(-/-)  mice that have exaggerated
      alloantibody responses. We found that previous sensitization to donor
      alloantigens resulted in the development of antidonor alloantibody (alloAb) with
      accelerated kinetics. Nevertheless, the numbers of alloantibody-secreting cells
      and the serum titers of antidonor IgG alloantibody were equivalent in sensitized
      and nonsensitized recipients 6 weeks after transplantation. Regardless of
      recipient sensitization status, the spleen contained higher numbers of donor
      reactive ASCs than bone marrow at days 7-21 after transplantation. Furthermore,
      individual spleen ASCs produced more antidonor IgG alloantibody than bone marrow
      ASCs. Taken together, our results indicate that the spleen rather than bone
      marrow is the major source of donor-reactive alloAb early after transplantation
      in both sensitized and nonsensitized recipients.

PMID- 22420369
TI  - A difficult diagnosis: drug-induced subacute cutaneous lupus erythematosus (SCLE)
      triggered by omeprazole in a patient with pre-existing idiopathic SCLE.

PMID- 22420370
TI  - The regulations of Drosophila phototransduction.
AB  - This is the first of two reviews that include some of the studies that we,
      members of the Pak lab and collaborators, carried out from 1998 to 2010 on the
      functional and physical interactions among several Drosophila phototransduction
      components. The report includes our studies on the regulations and/or the
      functions of arrestin II (Arr2), norpA (PLC), inactivation no afterpotential D
      (INAD), transient receptor potential (TRP), TRP-like (TRPL), inactivation no
      afterpotential E (INAE), and Porin.

PMID- 22420371
TI  - Effect of osteoporosis on periodontal therapy among post-menopausal women.
AB  - OBJECTIVE: This intervention study aimed to investigate the effect of
      osteoporosis on periodontal condition among 48 post-menopausal women undergoing
      periodontal therapy. MATERIAL AND METHODS: The experimental group, which
      underwent non-surgical periodontal therapy, was composed of 16 women with
      periodontitis to be treated, and the control group was formed by 32 women without
      periodontitis. Oral condition was assessed on three occasions: at the start of
      the treatment (first examination), 1 month (first re-examination) and 4 months
      after the end of the therapy (second re-examination). In the second re
      examination, recurrence of periodontal disease was evaluated by comparing the
      clinical measurements obtained pre- and post-treatment. The diagnosis of
      osteoporosis was made by investigating densitometry reports obtained previously.
      Descriptive analysis, analysis of variance and the Bonferroni post hoc test were
      applied to the data gathered, with statistical significance level of 5%. RESULTS:
      The frequency of periodontitis was 50% in the treated group and 25% in the group
      without periodontitis. In both groups, this recurrence was greater in subjects
      with osteoporosis (37.5 and 18.75%, respectively) than in the individuals without
      osteoporosis (12.5 and 6.25%, respectively). CONCLUSIONS: The preliminary results
      indicate that osteoporosis possibly has an influence on periodontal condition
      among individuals undergoing non-surgical periodontal treatment.

PMID- 22420372
TI  - Disease control and health systems in low- and middle-income countries: enhancing
      positive interrelation.
AB  - There is a growing interest in improving the relationship between disease control
      programmes and the rest of the health system in low- and middle-income countries.
      This short study seeks to contribute to this movement by providing a multi
      dimensional approach for policy-makers and researchers. It recognizes the
      different and often conflicting perspectives in health systems held by
      stakeholders. Two such perspectives are those of disease control programmes and
      health systems. Both are based on perceived health needs and put forward
      requirements on each other through resource demands and organizational needs.
      Failure to reconcile these perspectives can lead to health system fragmentation.
      This study proposes a framework to address the importance of mutual support
      across stakeholder perspectives, striving to understand and analyse the
      consequences of their reciprocal views. In doing this, the study stresses the
      importance of common understanding around health system values, the political
      interplay between stakeholders, the contextual setting and the need to integrate
      research and capacity development in this area.

PMID- 22420373
TI  - Three cases of neuroborreliosis misdiagnosed as giant cell arteritis.

PMID- 22420374
TI  - Epidural ketamine in the dromedary camel.
AB  - OBJECTIVE: To evaluate the clinical and physiological effects of epidural
      injection of ketamine in camels. STUDY DESIGN: Randomized prospective study.
      ANIMALS: Ten healthy immature male dromedary camels. METHODS: Ketamine was
      administered epidurally at doses of 1 and 2 mg kg(-1) (five animals in each
      treatment). The drug was injected into the first intercoccygeal epidural space.
      Anti-nociception, sedation, ataxia, and effect on cardiopulmonary, rectal
      temperature and some selected haematological parameters were recorded at
      different intervals before (baseline) and after the drug administration. Data
      were analyzed by anova or U Mann-Whitney tests, as relevant and significance was
      taken as p < 0.05. RESULTS: Epidural ketamine at the 2 mg kg(-1) dose produced
      complete anti-nociception in the tail, anus and perineum, whilst the 1 mg kg(-1)
      dose produced complete anti-nociception only in the tail. Epidural ketamine
      resulted in mild to moderate sedation at the 1 mg kg(-1) dose and deep sedation
      at the 2 mg kg(-1) dose. Ataxia was observed in all test subjects and was severe,
      resulting in recumbency, in the 2 mg kg(-1) group. Respiratory rate and rectal
      temperature did not change significantly after injection of either treatment.
      Following epidural injection of 2 mg kg(-1) of ketamine, heart rate increased
      significantly from the pre-injection baseline of 55 +/- 2 to 76 +/- 4 (mean +/-
      SD) beats minute(-1), but after the lower dose changes were not significant. The
      only significant changes in measured haematologic parameters were decreases in
      total erythrocyte count at 45 minutes and total leukocyte count from 45-75
      minutes, in the 2 mg kg(-1) group. CONCLUSION: Epidural ketamine injection was
      associated with caudal anti-nociception, sedation and ataxia in the dromedary
      camels; the intensity and duration of which was dose dependent. CLINICAL
      RELEVANCE: Neither of the doses of epidural ketamine injection in our study was
      applicable for standing surgical procedures in dromedary camels.

PMID- 22420375
TI  - Regulation of TGF-beta receptor activity.
AB  - TGF-beta signaling regulates diverse cellular processes, including cell
      proliferation, differentiation, apoptosis, cell plasticity and migration. Its
      dysfunctions can result in various kinds of diseases, such as cancer and tissue
      fibrosis. TGF-beta signaling is tightly regulated at different levels along the
      pathway, and modulation of TGF-beta receptor activity is a critical step for
      signaling regulation. This review focuses on our recent understanding of
      regulation of TGF-beta receptor activity.

PMID- 22420376
TI  - Base-catalyzed direct conversion of dipyrromethanes to 1,9-dicarbinols: a [2 + 2]
      approach for porphyrins.
AB  - A variant of the MacDonald approach was devised for the synthesis of porphyrins.
      A new base-catalyzed one-step synthesis of 1,9-dipyrromethane-dicarbinols was
      achieved by Friedel-Crafts alkylation of dipyrromethanes using commercially
      available ethyl glyoxylate solution in toluene. This method avoids the use of
      acid chlorides, Grignard reagents, borohydride reductions, and acidic conditions.
      The [2 + 2] condensation of dipyrromethanedicarbinols and dipyrromethanes yielded
      5,15-di(ethoxycarbonyl)porphyrins.

PMID- 22420377
TI  - Validity and reproducibility of folate and vitamin B(12) intakes estimated from a
      self-administered diet history questionnaire in Japanese pregnant women.
AB  - BACKGROUND: No validated dietary questionnaire for assessing folate and vitamin
      B(12) intakes during pregnancy is available in Japan. We evaluated the validity
      and reproducibility of intakes of folate and vitamin B(12) estimated from a self
      administered diet history questionnaire (DHQ) in Japanese pregnant women.
      METHODS: A sample of 167 healthy subjects with singleton pregnancies in the
      second trimester was recruited at a private obstetric hospital in metropolitan
      Tokyo from June to October 2008 (n = 76), and at a university hospital in Tokyo
      from June 2010 to June 2011 (n = 91). The dietary intakes of folate and vitamin
      B(12) were assessed using the DHQ. The serum concentrations of folate and vitamin
      B(12) were measured as reference values in the validation study. To assess the
      reproducibility of the results, 58 pregnant women completed the DHQ twice within
      4-5 week interval. RESULTS: Significantly positive correlations were found
      between energy-adjusted intakes and serum concentrations of folate and vitamin
      B(12) (r = 0.286, p < 0.001 and r = 0.222, p = 0.004, respectively). After
      excluding the participants with nausea (n = 121), the correlation coefficient for
      vitamin B(12) increased to 0.313 (p = 0.001). When participants were classified
      into quintiles based on intakes and serum concentrations of folate and vitamin
      B(12), approximately 60% were classified in the same or adjacent quintile. The
      intraclass correlation coefficients of the two-time DHQ were 0.725 for folate and
      0.512 for vitamin B(12). CONCLUSION: The present study indicated that the DHQ had
      acceptable validity and reproducibility for assessing folate and vitamin B(12)
      intakes in Japanese pregnant women.

PMID- 22420379
TI  - Blood donation in Morocco: a 20-year retrospective study of blood collection in
      the Rabat blood centre.
AB  - OBJECTIVES: We trace the history of blood donors and the recruitment strategies
      developed between 1988 and 2008 in the regional blood transfusion centre of
      Rabat. Beside, we draw a distribution map of the blood donors' population in
      Morocco during the year 2008. BACKGROUND: Limited resource countries face
      considerable obstacles to ensuring a safe blood supply and safe blood
      transfusions. Many countries used and some of them still depend on replacement
      blood donors. METHODS: Data published in this article had been collected from the
      CRTS of Rabat archives and reports. Data from all the 16 regional blood
      transfusion centres were collected from the report annually presented by the
      different regions. RESULTS: We found that during the 20 years period studied, the
      number of blood units collected by Rabat recorded many fluctuations. In the mean
      time, many measures were taken to promote the recruitment of voluntary blood
      donors. The proportion of these later jumped from 16.55% in 1988 to reach almost
      80% in 2008. Beside, the whole country's blood collection map for the year 2008
      showed that 190 504 of whole blood units were collected. This means that there
      are only six donations per 1000 people. CONCLUSION: This is the first study
      conducted in Morocco that provided detailed information on ongoing trends in
      blood donor profiles. The creation and development of new mobile drive units and
      maintaining them over time was the key to increase the collection of blood units
      from voluntary, non-remunerated blood donors.

PMID- 22420380
TI  - I love rheumatologic cases!

PMID- 22420381
TI  - New autism spectrum criteria proposed: some who qualify for diagnosis might not
      after 2013.

PMID- 22420382
TI  - A 2-month-old infant with hyperbilirubinemia.

PMID- 22420383
TI  - Diagnostic dilemmas of a herpes-like rash in healthy neonates.

PMID- 22420378
TI  - Independent evolution of macrophage-tropism and increased charge between HIV-1 R5
      envelopes present in brain and immune tissue.
AB  - BACKGROUND: Transmitted HIV-1 clade B or C R5 viruses have been reported to
      infect macrophages inefficiently, while other studies have described R5 viruses
      in late disease with either an enhanced macrophage-tropism or carrying envelopes
      with an increased positive charge and fitness. In contrast, our previous data
      suggested that viruses carrying non-macrophage-tropic R5 envelopes were still
      predominant in immune tissue of AIDS patients. To further investigate the tropism
      and charge of HIV-1 viruses in late disease, we evaluated the properties of HIV-1
      envelopes amplified from immune and brain tissues of AIDS patients with
      neurological complications. RESULTS: Almost all envelopes amplified were R5.
      There was clear compartmentalization of envelope sequences for four of the five
      subjects. However, strong compartmentalization of macrophage-tropism in brain was
      observed even when brain and immune tissue envelope sequences were not
      segregated. R5 envelopes from immune tissue of four subjects carried a higher
      positive charge compared to brain envelopes. We also confirm a significant
      correlation between macrophage tropism and sensitivity to soluble CD4, a weak
      association with sensitivity to the CD4 binding site antibody, b12, but no clear
      relationship with maraviroc sensitivity. CONCLUSIONS: Our study shows that non
      macrophage-tropic R5 envelopes carrying gp120s with an increased positive charge
      were predominant in immune tissue in late disease. However, highly macrophage
      tropic variants with lower charged gp120s were nearly universal in the brain.
      These results are consistent with HIV-1 R5 envelopes evolving gp120s with an
      increased positive charge in immune tissue or sites outside the brain that likely
      reflect an adaptation for increased replication or fitness for CD4+ T-cells. Our
      data are consistent with the presence of powerful pressures in brain and in
      immune tissues selecting for R5 envelopes with very different properties; high
      macrophage-tropism, sCD4 sensitivity and low positive charge in brain and non
      macrophage-tropism, sCD4 resistance and high positive charge in immune tissue.

PMID- 22420385
TI  - Pediatric palliative care in the medical home.

PMID- 22420386
TI  - Developments in imaging: 'a huge difference in primary care'.

PMID- 22420387
TI  - A conversation with James A. Stockman III, MD. Interview by Stanford T. Shulman.

PMID- 22420389
TI  - Leukaemic variant of cutaneous T-cell lymphoma with CD3- CD4+ phenotype.

PMID- 22420390
TI  - An otalgia pain syndrome, the anterolateral tip of the mastoid syndrome (ATOMS):
      diagnosis and response to treatment.
AB  - INTRODUCTION: Otalgia is a common presenting disorder. We describe a pain entity
      characterized by localized pain at the anterolateral tip of the mastoid (ATOM),
      which can be diagnosed by location and response to lidocaine (Xylocaine)
      injection. Long-term therapeutic results are described following a single
      injection of lidocaine. We compared 11 patients with this pain location to 24
      patients with nonspecific otalgia. MATERIALS AND METHODS: In a tertiary otology
      centre, patients with severe ATOM-related pain were treated using 3 cc of 1%
      lidocaine injection; pain scores were measured before and afterward with a
      questionnaire, which also probed the effects on general lifestyle or possible
      causative factors. A consecutive group of 64 patients referred to the clinic, who
      also filled out the questionnaire, were used as a reference group. RESULTS: The
      average severity of the pain was 7.6 of 10 prior to injection, and at 1 hour,
      this fell to 1.5, at 1 day to 2, at 1 week to 0.6, and to 1.9 at the 10-month
      follow-up. The duration of the pain, if intermittent, also fell significantly. Of
      the 11 patients, 9 had previous ear surgery. There was a higher incidence of
      females, tooth grinding, and ear surgery in the ATOM group than in the non-ATOM
      otalgia group. CONCLUSIONS: ATOM pain is another cause of otalgia symptoms that
      should be recognized and often responds to local anesthetic injection.

PMID- 22420391
TI  - Eustachian tube obliteration in translabyrinthine vestibular schwannoma excision:
      cerebrospinal fluid rhinorrhea and middle ear status.
AB  - OBJECTIVES: To assess the incidence of cerebrospinal fluid (CSF) rhinorrhea by
      systematic eustachian tube (ET) obliteration at the time of a translabyrinthine
      vestibular schwannoma (VS) excision and to evaluate its effect on the middle ear
      and on the tympanic membrane and if it is well tolerated by patients. STUDY
      DESIGN: Retrospective study. SETTING: Tertiary care centre. PATIENTS: Group 1 (57
      patients) and group 2 (87 patients) underwent translabyrinthine VS excision with
      and without systematic ET obliteration, respectively. MAIN OUTCOME MEASURES:
      Petrous apex pneumatization level and postoperative CSF leak were evaluated.
      Group 1 patients had a late postoperative otologic examination, tympanometric
      test, Valsalva manoeuvre, and ear symptom evaluation. RESULTS: There were six
      cases of CSF rhinorrhea in group 2, whereas no cases were observed in group 1 (p 
      =  .043), despite its larger tumour grade (p  =  .002). In group 2, CSF
      rhinorrhea was absent at pneumatization level 1. Three of six CSF rhinorrhea
      cases developed meningitis. None of the 27 tested patients of group 1
      demonstrated a tympanic membrane retraction or a positive Valsalva manoeuvre.
      Tympanometry showed a type A curve (2 patients), a type As curve (14 patients),
      and a type B curve (11 patients). Air volumes and air pressures of the operated
      ears were lower than those of the nonoperated ears (p < .001). CONCLUSION:
      Patients of group 1 tolerated the procedure well, with preserved tympanic
      membrane compliance. Bidirectional air exchange throughout a normal middle ear
      mucosa explains this fact. We recommend obliteration of both the petrous apex
      cells and ET in all cases of petrous apex pneumatization levels 2 to 4.

PMID- 22420392
TI  - Automated hearing tests: applying the otogram to patients who are difficult to
      test.
AB  - OBJECTIVE: The Otogram is an automated audiometer capable of determining air and
      bone conduction thresholds with masking when appropriate. The manufacturer claims
      that testing can be done in a quiet physician's consultation room without a sound
      treated booth. We aimed to test the validity of the Otogram on "difficult-to
      test" patients, all of whom require masking. METHODS: Twenty-eight difficult-to
      test patients underwent three audiograms: two by an audiologist and one by the
      Otogram. First, audiograms performed by the audiologists were compared,
      establishing test-retest reliability. Second, audiograms performed by the Otogram
      were compared to those of the audiologists. We calculated the percentage of pure
      tone thresholds that were in agreement by 10 dB. Weighted kappa statistical
      analyses demonstrated levels of agreement. RESULTS: Comparisons between
      audiologists demonstrated a very high degree of agreement. More than 90% of air
      and bone conduction thresholds fell within 10 dB of each other. Comparisons
      between audiologists and the Otogram also demonstrated a high degree of
      agreement. CONCLUSIONS: The Otogram has the capability to accurately ascertain
      air and bone conduction thresholds. It appropriately used masking when indicated.
      The Otogram has great potential as a diagnostic tool to improve access to health
      care, especially where hearing test facilities are limited or unavailable.

PMID- 22420393
TI  - Head and neck incidentalomas on positron emission tomographic scanning: ignore or
      investigate?
AB  - BACKGROUND AND OBJECTIVE: Incidental head and neck abnormalities are increasingly
      detected with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET).
      Incidental thyroid lesions on PET are described in many studies; however, no
      reports have definitively identified incidental findings in multiple head and
      neck sites. The aim of this study was to (1) review the related literature, (2)
      identify the incidence and significance of head and neck incidentalomas on
      PET/computed tomography (CT) scanning, and (3) attempt to establish management
      recommendations for head and neck PET incidentalomas. STUDY DESIGN: Retrospective
      study. SETTING: Tertiary care centre. METHODS: Head and neck incidentaloma cases
      from whole-body 18F-FDG PET/CT scans were reviewed based on specific inclusion
      criteria from January 2009 to January 2010 at the Jewish General Hospital. The
      patients had been scanned for known or suspected malignant lesions in non-head
      and neck sites. Patients with incidental head and neck abnormalities were
      identified. RESULTS: The scans of 38 of 1565 (2.43%) subjects who underwent FDG
      PET scanning for known or suspected cancer demonstrated head and neck
      incidentalomas. In 8 of 38 cases (21.05%), malignancies were discovered in the
      incidentaloma lesion (5 thyroid, 2 parotid, and 1 cervical lymph node), and all
      were new primary malignancies. Five of the 8 (62.5%) demonstrated significantly
      high standard uptake value (SUV). CONCLUSION: Head and neck PET/CT incidentalomas
      are quite common. A significantly high SUV strongly suggests the presence of
      malignancy. Head and neck incidentalomas merit consultation and further
      evaluation.

PMID- 22420394
TI  - Value of thyroid incidentalomas on positron emission tomographic scans among
      thyroidectomy patients.
AB  - OBJECTIVES: To evaluate the preoperative predictive value of a positive positron
      emission tomographic (PET) scan with respect to malignancy in future
      thyroidectomy candidates, particularly when the fine-needle aspiration biopsy
      (FNAB) results in indeterminate findings, and to establish the efficiency with
      which this can be incorporated as a preoperative marker and potentially
      contribute to a standardized scoring system for thyroid nodule patients. METHODS:
      This retrospective study examined 1048 thyroidectomy patients, of whom 45
      underwent PET with computed tomography for unrelated reasons, among which 13
      results were focally positive. The final pathology was evaluated and compared to
      this result to determine the correlation. RESULTS: All patients with positive PET
      results were shown postthyroidectomy to have a thyroid malignancy (13 of 13),
      corresponding to a positive predictive value of 100%. There was no correlation
      between a negative PET scan and malignancy, however. When integrating the PET
      scan criteria in the McGill Scoring System, 4 of these 13 were shifted into a
      high chance of malignancy group, allowing a more accurate assessment of their
      risk than they might have previously received. CONCLUSION: In comparison with
      previous data, our results indicate a strong relationship between a positive PET
      scan and malignancy. If available and used in conjunction with the other
      preoperative diagnostic tools (outlined by the McGill Thyroid Nodule Scoring
      System), this test can hold significant merit in determining a therapeutic
      strategy, particularly in the face of an indeterminate FNAB.

PMID- 22420395
TI  - Endoscopic transnasal drainage of frontal epidural abscesses.
AB  - BACKGROUND: Although rare, sinogenic intracranial epidural frontal abscesses
      remain a serious and potentially life-threatening complication of sinusitis.
      Traditional therapy involves a combination of intravenous antibiotics, sinus
      surgery, and neurosurgical drainage through an external approach. OBJECTIVE: In
      this report, we present a technique in which a purely endoscopic transnasal
      approach was used to treat both the sinusitis and the intracranial abscess. Four
      cases are discussed illustrating the technique and its outcomes. METHODS: In all
      cases, endoscopic sinus surgery was performed to treat underlying sinus disease.
      Next, under image guidance, an endoscopic, intranasal opening through the skull
      base was performed for intracranial access and abscess drainage. RESULTS: Our
      patients tolerated this procedure well and fully recovered with resolution of all
      presenting neurologic features. CONCLUSION: This approach may offer a safe and
      effective alternative to frontal craniotomy for selected cases and can result in
      lower postoperative morbidity than traditional approaches.

PMID- 22420396
TI  - Diagnosing allergic rhinitis: effectiveness of the physical examination in
      comparison to conventional skin testing.
AB  - OBJECTIVE: To evaluate the effectiveness of physical examination alone in
      diagnosing nasal allergic patients. DESIGN: A cross-sectional study of 15
      consecutive evaluable patients. SETTING: A tertiary care otolaryngology clinic at
      the Jewish General Hospital, McGill University, Montreal. METHODS: All patients
      were assessed by three physicians in random order. Each conducted a specific
      examination, made a clinical impression, and then took a directed history to make
      a second impression. Both impressions were compared to skin testing. Multivariate
      regression analyses assessed the linear relationships of both examination and
      history variables to impressions and skin testing results. Fleiss kappa tests
      assessed interrater reliabilities. MAIN OUTCOME MEASURES: Accuracy in diagnosing
      allergic rhinitis by examination alone and inter-rater reliability in this
      diagnosis. RESULTS: When comparing physical examination variables to history
      variables relative to the second impression, history variables had a stronger
      relationship (R2  =  .90 vs .52). This was also true when comparing both sets of
      variables to skin testing (R2  =  .81 vs .60). The interrater reliability of
      physical examination variables was poorer than that of the history variables
      (.377 and .494, respectively). Taking all physicians, the average sensitivity,
      specificity, positive predictive value, and negative predictive value of the
      history impression were all higher than those of the examination impression.
      CONCLUSION: Physical examination alone yields unreliable and inconsistent results
      in diagnosing allergic rhinitis. This is likely secondary to the relative
      subjectivity involved in evaluating the nasal cavity. Adding a history to the
      examination is essential to increase diagnostic accuracy.

PMID- 22420397
TI  - Can we predict a difficult intubation in cleft lip/palate patients?
AB  - OBJECTIVE: To find predictors of a difficult intubation in infants with an
      isolated or a syndromic cleft lip/palate. STUDY DESIGN: Retrospective review:
      single-blind trial. SETTINGS: Tertiary care centre. METHODS: A total of 145
      infants born with cleft lip/palate were enrolled. Three clinical and seven
      lip/palate anatomic parameters were evaluated. The grade of intubation was
      determined by the anesthesiologist at the time of the labioplasty/staphylorrhaphy
      surgery at 3 and 10 months, respectively. MAIN OUTCOME MEASURE: Intubation grade.
      RESULTS: The relative risk of a difficult intubation in the cleft lip, cleft
      palate without the Pierre Robin sequence, cleft lip-palate, and cleft palate with
      Pierre Robin sequence groups was 0, 2.7, 10, and 23%, respectively. The infants
      born with the Pierre Robin sequence had a statistically significant higher
      intubation grade. The degree of difficulty was increased in cases with early
      airway and feeding problems (p < .0001). Within the group of cleft palate
      patients without any lip malformation, a wider cleft was associated with a higher
      intubation grade with statistical significance (p  =  .0323). CONCLUSIONS:
      Infants born with Pierre Robin sequence have a statistically significantly higher
      risk of difficult intubation. Within this group, of all the studied factors, a
      clinical history of early airway and feeding problems was the best predictor of a
      difficult endotracheal intubation. In cleft palate patients without any cleft
      lip, larger width of the cleft is also a significant predictor.

PMID- 22420398
TI  - Pediatric inferior turbinoplasty with or without adenoidectomy: preliminary
      report on improvement of quality of life, symptom control, and safety.
AB  - OBJECTIVE: To determine quality of life (QOL) improvement, symptom control, and
      safety after inferior turbinoplasty (IT) with or without adenoidectomy (Ad) in
      children. DESIGN: Retrospective uncontrolled cohort study. SETTING: Tertiary care
      pediatric hospital. METHODS: A prospective database was searched. The database
      contained information regarding age, gender, other diagnoses, and complications.
      Inclusion criteria were (1) children who presented with chronic rhinitis (CR)
      refractory to medical treatment and (2) children who underwent IT with or without
      Ad. MAIN OUTCOME MEASURES: The Glasgow Children's Benefit Inventory (GCBI) was
      used to assess QOL improvement. The GCBI calculates a score ranging from -100
      (maximum harm) to +100 (maximum benefit), with 0 representing no change after
      surgery. RESULTS: Eighty-seven patients were identified. Forty-one were excluded
      owing to concurrent lingual tonsillectomy or septal or sinus surgery. Forty-six
      consecutive patients were included. Data were obtained from all 46 patients
      (100%). The average age was 10 years, with 15 females and 31 males. One
      complication required admission. The GCBI scores showed that patients derived
      benefit in all domains (median GCBI 28.1, range -6.3 to 93.8). CONCLUSION:
      Preliminary results indicate that IT with or without Ad is a safe, beneficial
      procedure for CR in children. The impact of IT on QOL is comparable to that of
      well-established operations in otolaryngology.

PMID- 22420399
TI  - Cosmetic and functional outcomes after preoperative tissue expansion of radial
      forearm free flap donor sites: a cohort study.
AB  - INTRODUCTION: The use of the DynaClose topical tissue expansion device for
      closure of radial forearm free flap (RFFF) donor sites has been demonstrated to
      significantly reduce healing time and postoperative pain compared to the
      traditional use of a split-thickness skin graft. However, long-term cosmetic and
      functional outcomes are not known. OBJECTIVE: The objective of this study was to
      test the hypothesis that using a new method of donor site management will result
      in improved cosmesis of RFFF donor sites as assessed by both patients and expert
      observers without resulting in a reduction in the function of the patients'
      forearm. METHODS: A cohort of 25 patients previously randomized to either the
      treatment (tissue expansion) or the control group were assessed at 10 months. The
      Patient and Observer Scar Assessment Scale (PAOSAS) was used to assess forearm
      scars, whereas the Michigan Hand Outcomes Questionnaire assessed hand function.
      RESULTS: Expert observers noted improved scar cosmesis in the treatment group (p 
      =  .013), with primary closure having the best cosmetic outcome, followed by
      local full-thickness skin graft closure (p < .001). There was no statistically
      significant improvement in cosmesis as assessed by patients (p  =  .03) or
      differences in Michigan Hand Outcomes Questionnaire scores between treatment
      groups (p  =  .57). CONCLUSION: Using an inexpensive, noninvasive preoperative
      tissue expansion device safely results in improved cosmetic outcomes as assessed
      by expert observers, without any significant functional forearm and hand
      deficits.

PMID- 22420400
TI  - Injection laryngoplasty: a serious reaction to hyaluronic acid.

PMID- 22420401
TI  - Late complication in posterior tibial artery free flap in reconstruction of the
      oral cavity.

PMID- 22420402
TI  - Laryngeal hirudiniasis as an unusual cause of massive hemoptysis.

PMID- 22420403
TI  - Gender-dependent associations of uric acid levels with a polymorphism in SLC2A9
      in Han Chinese patients.

PMID- 22420405
TI  - Refractory cystoid macular oedema due to intraocular lens haptic perforating the
      iris.
AB  - Cystoid macular oedema is a well-known complication of cataract surgery
      associated with intraocular lens decentration or dislocation. A 55-year-old man,
      who had undergone a phacoemulsification and intraocular lens implantation surgery
      two months previously was referred because of reduced vision in the right eye.
      Ocular examination revealed that one of the haptics had perforated the iris at 6
      o'clock. There was cystoid macular oedema of the right eye. A topical non-steroid
      anti-inflammatory drug, followed by intravitreal injections did not produce a
      significant regression. Finally, the haptic was repositioned surgically and the
      macular oedema dramatically resolved. Correct placement of the intraocular lens
      might avoid post-operative complications including cystoid macular oedema.

PMID- 22420404
TI  - Role of the gerA operon in L-alanine germination of Bacillus licheniformis
      spores.
AB  - BACKGROUND: The genome of Bacillus licheniformis DSM 13 harbours three
      neighbouring open reading frames showing protein sequence similarities to the
      proteins encoded from the Bacillus subtilis subsp. subtilis 168 gerA operon,
      GerAA, GerAB and GerAC. In B. subtilis, these proteins are assumed to form a
      germinant receptor involved in spore germination induced by the amino acid L
      alanine. RESULTS: In this study we show that disruption of the gerAA gene in B.
      licheniformis MW3 hamper L-alanine and casein hydrolysate-triggered spore
      germination, measured by absorbance at 600 nm and confirmed by phase contrast
      microscopy. This ability was restored by complementation with a plasmid-borne
      copy of the gerA locus. Addition of D-alanine in the casein hydrolysate
      germination assay abolished germination of both B. licheniformis MW3 and the
      complementation mutant. Germination of both B. licheniformis MW3 and the gerA
      disruption mutant was induced by the non-nutrient germinant Ca2+-Dipicolinic
      acid. CONCLUSIONS: These results demonstrate that the B. licheniformis MW3 gerA
      locus is involved in germination induced by L-alanine and potentially other
      components present in casein hydrolysate.

PMID- 22420406
TI  - Animal livestock and the risk of hospitalized diarrhoea in children under 5 years
      in Vietnam.
AB  - OBJECTIVE: To investigate the association between environmental exposure to
      livestock and incidence of diarrhoea among Vietnamese children. METHODS: A
      population-based cohort of 353,525 individuals, living in 75,828 households in
      Khanh Hoa Province, Vietnam, with baseline data covering geo-referenced
      information on demography, socio-economic status and household animals was
      investigated. Geographic information system was applied to calculate the density
      of livestock. The data were linked to hospitalized diarrhoea cases of children
      under 5 years recorded at two hospitals treating patients from the area as
      inpatients in the study area. RESULTS: Overall, 3116 children with diarrhoea were
      hospitalized during the study period. The incidence of diarrhoea hospitalization
      was 60.8/1000 child-years. Male gender, age <2 years, higher number of household
      members and lack of tap water were significantly associated with an increased
      risk of diarrhoea. There was no evidence that ownership of livestock increased
      the risk of diarrhoea. In spatial analysis, we found no evidence that a high
      density of any animals was associated with an increased risk of diarrhoea.
      CONCLUSIONS: Exposure to animals near or in households does not seem to
      constitute a major risk for diarrhoea in children under the age of 5 in Vietnam.
      Public health interventions to reduce childhood diarrhoea burden should focus on
      well-recognized causes such as sanitation, personal hygiene, access to adequate
      clean water supply and vaccination.

PMID- 22420407
TI  - Acute genetic manipulation of neuronal activity for the functional dissection of
      neural circuits-a dream come true for the pioneers of behavioral genetics.
AB  - Abstract: This review summarizes technical development of the functional
      manipulation of specific neural circuits through genetic techniques in
      Drosophila. Long after pioneers' efforts for the genetic dissection of behavior
      using this organism as a model, analyses with acute activation of specific neural
      circuits have finally become feasible using transgenic Drosophila that expresses
      light-, heat-, or cold-activatable cation channels by xxx/upstream activation
      sequence (Gal4/UAS)-based induction system. This methodology opened a new avenue
      to dissect functions of neural circuits to make dreams of the pioneers into
      reality.

PMID- 22420408
TI  - Exploiting the inter-strain divergence of Fusarium oxysporum for microbial
      bioprocessing of lignocellulose to bioethanol.
AB  - Microbial bioprocessing of lignocellulose to bioethanol still poses challenges
      in terms of substrate catabolism. A targeted evolution-based study was undertaken
      to determine if inter-strain microbial variability could be exploited for
      bioprocessing of lignocellulose to bioethanol. The microorganism studied was
      Fusarium oxysporum because of its capacity to both saccharify and ferment
      lignocellulose. Strains of F. oxysporum were isolated and assessed for their
      genetic variability. Using optimised solid-state straw culture conditions,
      experiments were conducted that compared fungal strains in terms of their growth,
      enzyme activities (cellulases, xylanase and alcohol dehydrogenase) and yield of
      bioethanol and the undesirable by-products acetic acid and xylitol. Significant
      inter-strain divergence was recorded in regards to the capacity of studied F.
      oxysporum strains to produce alcohol from untreated straw. No correlation was
      observed between bioethanol synthesis and either the biomass production or
      microbial enzyme activity. A strong correlation was observed between both acetic
      acid and xylitol production and bioethanol yield. The level of diversity recorded
      in the alcohol production capacity among closely-related microorganism means that
      a targeted screening of populations of selected microbial species could greatly
      improve bioprocessing yields, in terms of providing both new host strains and
      candidate genes for the bioethanol industry.

PMID- 22420409
TI  - Statin therapy, myopathy and exercise--a case report.
AB  - In a bid to reduce the morbidity and mortality associated with coronary artery
      disease, statin therapy has become a cornerstone treatment for patients with
      dyslipideamia. Statins, or HMG-CoA reductase inhibitors, are effective in
      blocking hepatic synthesis of cholesterol and are generally regarded as safe.
      Although rare, severe adverse side effects such as rhabdomyolysis have been
      reported, however, the more common complaint from patients is that related to
      myopathy. There is also mounting evidence that exercise may exacerbate these side
      effects, however the mechanisms are yet to be fully defined and there is
      controversy regarding the role that inflammation may play in the myopathy. This
      paper reports a patients experience during 6 months of simvastatin therapy and
      provides some insight into the white cell count (inflammation) following two
      bouts of moderate intensity exercise before and during statin therapy. It also
      highlights the need for rehabilitation practitioners to be aware of the adverse
      effects of statins in exercising patients.

PMID- 22420410
TI  - Structure elucidation of a new natural diketopiperazine from a Microbispora
      aerata strain isolated from Livingston Island, Antarctica.
AB  - A new natural diketopiperazine (1) was obtained from the culture broth of
      Microbispora aerata strain imbas-11A, isolated from penguin excrements collected
      on the Antarctic Livingston Island. Compound 1 was purified consecutively by
      solvent extraction, silica gel column chromatography and preparative HPLC. The
      structure of the compound was elucidated by 1D and 2D NMR experiments and mass
      spectrometric investigations. The absolute configuration of compound 1 was
      determined by amino acid analysis and NOESY correlations. A low antiproliferative
      and cytotoxic effect of trans-cyclo-(D-tryptophanyl-L-tyrosyl) (1) was determined
      with L-929 mouse fibroblast cells, K-562 human leukemia cells and HeLa human
      cervix carcinoma. Trans-cyclo-(D-tryptophanyl-L-tyrosyl) (1) did not show
      antimicrobial activity at a concentration of 50 ug per disc against Bacillus
      subtilis, Staphylococcus aureus, Streptomyces viridochromogenes, Escherichia
      coli, Candida albicans and Mucor miehei.

PMID- 22420411
TI  - Matrix isolation spectroscopic and theoretical study of carbon dioxide activation
      by titanium oxide molecules.
AB  - The reactions of titanium monoxide and dioxide molecules with carbon dioxide were
      investigated by matrix isolation infrared spectroscopy. It was found that the
      titanium monoxide molecule is able to activate carbon dioxide to form the
      titanium dioxide-carbon monoxide complex upon visible light excitation via a
      weakly bound TiO(eta(1)-OCO) intermediate in solid neon. In contrast, the
      titanium dioxide molecule reacted with carbon dioxide to form the titanium
      monoxide-carbonate complex spontaneously on annealing. Theoretical calculations
      predicted that both activation processes are thermodynamically exothermic and
      kinetically facile.

PMID- 22420412
TI  - Synthesis of sulfur-containing heterocycles through oxidative carbon-hydrogen
      bond functionalization.
AB  - Vinyl sulfides react rapidly and efficiently with 2,3-dichloro-5,6-dicyano-1,4
      benzoquinone (DDQ) to form alpha,beta-unsaturated thiocarbenium ions through
      oxidative carbon-hydrogen bond cleavage. These electrophiles couple with appended
      pi-nucleophiles to yield sulfur-containing heterocycles through carbon-carbon
      bond formation. Several nucleophiles are compatible with the procedure, and the
      reactions generally proceed through readily predictable transition states.

PMID- 22420413
TI  - Molecular background of D-negative phenotype in the Tunisian population.
AB  - BACKGROUND: Most studies of the molecular basis of Rhesus D-negative phenotype
      have been conducted in Caucasian and African populations. A comprehensive survey
      of RHD alleles was lacking in people from North Africa (Tunisians, Moroccans and
      Algerians) which could be very efficient for managing donors and patients
      carrying an RHD molecular variant. We analyse the molecular background of D
      negative population in Tunisia in the present study. MATERIALS AND METHODS: Blood
      samples were collected from native Tunisians. A total of 448 D-negative donors
      from different regions of Tunisia were analysed by RHD genotyping according to an
      adopted strategy using real-time PCR, ASP-PCR and sequencing. RESULTS: Among the
      448 D-negative samples, 443 were phenotyped unequivocally as true D-negative
      including three molecular backgrounds which were RHD gene deletion (n = 437),
      RHDpsi pseudogene (n = 2) and RHD-CE-D hybrid gene (n = 4) with the respective
      frequencies of 0.9900, 0.0023 and 0.0046. The remaining five samples, in
      discordance with the serological results, were identified as two weak D type 11,
      one weak D type 29, one weak D type 4.0 and one DBT-1 partial D. CONCLUSION: This
      study showed that the Tunisian population gets closer to Caucasians, given that
      the RHD gene deletion is the most prevalent cause of D-negative phenotype, but it
      is slightly different by the presence of the RHDpsi pseudogene which was found
      with a very low frequency compared with that described in the African population.
      Nevertheless, the relative occurrence of weak D variants among studied
      serologically D-negative samples make necessary the adaptation of RHD genotyping
      strategy to the spectrum of prevalent alleles.

PMID- 22420415
TI  - Methotrexate therapy, rheumatoid arthritis, and life-threatening liver
      complications: should we be monitoring more closely?

PMID- 22420417
TI  - Message framing and medium considerations for recruiting newly eligible teen
      organ donor registrants.
AB  - In response to the current organ shortage-and in an effort to increase the number
      of registered donors-the present campaign employed a direct-mail marketing
      strategy that registered 6908 individuals in the state's First-Person Consent
      Registry (FPCR). In evaluating the most effective of three mailers, 18-year-old
      individuals (N = 139,356) were randomly assigned to receive: (a) a letter from
      the Secretary of State (SoS); (b) a brochure from the SoS or (c) both. As
      hypothesized, the results revealed that exposure to the SoS letter only resulted
      in a greater registration rate than exposure to the SoS brochure only. Results
      also revealed that exposure to both the SoS letter and SoS brochure resulted in a
      greater registration rate than exposure to the SoS brochure only. No difference
      in registration rate emerged between exposure to the SoS letter and SoS brochure
      compared to exposure to the SoS letter only. Our results speak to the
      effectiveness of utilizing personalized direct-mail marketing strategies to
      promote organ donation with an emphasis on the practical implications of our
      findings for organ donation practitioners.

PMID- 22420414
TI  - The endogenous retrovirus ENS-1 provides active binding sites for transcription
      factors in embryonic stem cells that specify extra embryonic tissue.
AB  - BACKGROUND: Long terminal repeats (LTR) from endogenous retroviruses (ERV) are
      source of binding sites for transcription factors which affect the host
      regulatory networks in different cell types, including pluripotent cells. The
      embryonic epiblast is made of pluripotent cells that are subjected to opposite
      transcriptional regulatory networks to give rise to distinct embryonic and
      extraembryonic lineages. To assess the transcriptional contribution of ERV to
      early developmental processes, we have characterized in vitro and in vivo the
      regulation of ENS-1, a host adopted and developmentally regulated ERV that is
      expressed in chick embryonic stem cells. RESULTS: We show that Ens-1 LTR activity
      is controlled by two transcriptional pathways that drive pluripotent cells to
      alternative developmental fates. Indeed, both Nanog that maintains pluripotency
      and Gata4 that induces differentiation toward extraembryonic endoderm
      independently activate the LTR. Ets coactivators are required to support Gata
      factors' activity thus preventing inappropriate activation before epigenetic
      silencing occurs during differentiation. Consistent with their expression
      patterns during chick embryonic development, Gata4, Nanog and Ets1 are recruited
      on the LTR in embryonic stem cells; in the epiblast the complementary expression
      of Nanog and Gata/Ets correlates with the Ens-1 gene expression pattern; and Ens
      1 transcripts are also detected in the hypoblast, an extraembryonic tissue
      expressing Gata4 and Ets2, but not Nanog. Accordingly, over expression of Gata4
      in embryos induces an ectopic expression of Ens-1. CONCLUSION: Our results show
      that Ens-1 LTR have co-opted conditions required for the emergence of
      extraembryonic tissues from pluripotent epiblasts cells. By providing pluripotent
      cells with intact binding sites for Gata, Nanog, or both, Ens-1 LTR may promote
      distinct transcriptional networks in embryonic stem cells subpopulations and
      prime the separation between embryonic and extraembryonic fates.

PMID- 22420418
TI  - Communication skills training for health care professionals improves the adult
      orthopaedic patient's experience of quality of care.
AB  - RATIONALE: Despite the fact that communication has become a core topic in health
      care, patients still experience the information provided as insufficient or
      incorrect and a lack of involvement. OBJECTIVE: To investigate whether adult
      orthopaedic patients' evaluation of the quality of care had improved after a
      communication skills training course for healthcare professionals. DESIGN AND
      METHODS: The study was designed as an intervention study offering professionals
      training in communicating with patients and colleagues. The outcome was measured
      by assessing patients' experience of quality of care. Data were collected by
      means of a questionnaire and analysed using a linear regression model. Approval
      was obtained from the Danish Data Protection Agency. RESULTS: A total of 3133
      patients answered the questionnaire, 1279 before staff had attended courses and
      1854 in the postcourse period, with response rates of 67.8 and 77.8%,
      respectively. After the course period, significant increases in responses
      indicating 'considerable' improvement were recorded for 15/19 questions,
      nonsignificant increases were registered for 3/19 questions and a statistically
      significant decrease for one question. STUDY LIMITATIONS: This being an
      effectiveness study, it is deemed that the organizational changes taking place
      during the study period constitute no serious limitation. Response rates were
      comparable to those of other studies. CONCLUSION: Patients show increased
      satisfaction with the quality of health care after professionals have attended a
      communication skills training course, even when implemented in an entire
      department. PRACTICE IMPLICATIONS: We recommend that healthcare professionals are
      trained in patient-centred communication and that training is extended to the
      entire organization.

PMID- 22420419
TI  - Comparative study of microscopic charge dynamics in crystalline acceptor
      substituted oligothiophenes.
AB  - By performing microscopic charge transport simulations for a set of crystalline
      dicyanovinyl-substituted oligothiophenes, we find that the internal acceptor
      donor-acceptor molecular architecture combined with thermal fluctuations of
      dihedral angles results in large variations of local electric fields, substantial
      energetic disorder, and pronounced Poole-Frenkel behavior, which is unexpected
      for crystalline compounds. We show that the presence of static molecular dipoles
      causes large energetic disorder, which is mostly reduced not by compensation of
      dipole moments in a unit cell but by molecular polarizabilities. In addition, the
      presence of a well-defined pi-stacking direction with strong electronic couplings
      and short intermolecular distances turns out to be disadvantageous for efficient
      charge transport since it inhibits other transport directions and is prone to
      charge trapping.

PMID- 22420420
TI  - Photodynamic therapy for basal cell carcinomas in organ-transplant recipients.
AB  - The incidence of nonmelanoma skin cancer is significantly increased in recipients
      of solid-organ transplants. Photodynamic therapy (PDT) is a well-documented
      treatment option for superficial and selected nodular basal cell carcinomas
      (BCCs) in immunocompetent patients, but there are few reports describing PDT of
      BCCs in organ-transplant recipients (OTRs). We report a study of 18 OTRs with BCC
      on the head and trunk, who were treated with PDT, using methyl aminolevulinate as
      photosensitizer. There was only one recurrence during a total follow-up period of
      407 months. PDT seems to be an effective treatment option for BCC in
      immunosuppressed OTRs.

PMID- 22420421
TI  - A novel approach to facilitating balloon crossing chronic total occlusions: the
      "wire-cutting" technique.
AB  - BACKGROUND: Following successful guidewire passage, inability to cross the
      occluded lesion with a balloon is the most common cause of procedural failure for
      percutaneous recanalization of chronic total occlusions (CTOs). We sought to
      evaluate the efficacy of "wire-cutting" technique for facilitating the balloon
      passage through the lesion during CTO-percutaneous coronary intervention.
      METHODS: Sixteen consecutive patients with CTOs were treated by "wire-cutting"
      technique when a lubricious balloon could not be passed through the lesion after
      successful guidewire crossing. The main process of the "wire-cutting" technique
      involved: inserting 2 percutaneous transluminal coronary angioplasty (PTCA)
      guidewires (A and B) into the distal true lumen; advancing a balloon over
      guidewire A to the site of the occlusion abutting the proximal cap, the balloon
      was then inflated and guidewire B was pressed between the balloon and the
      proximal cap; rapidly withdrawing guidewire B produced a cutting power that
      crushed the proximal cap thus facilitating balloon crossing. Technique success
      was defined as balloon having crossed CTO lesions successfully after performing
      wire-cutting procedure. RESULTS: Both technical success and procedural success
      were obtained in 10 (62.5%) cases. Technique failure occurred in 6 (37.5%) cases,
      of which 2 were due to the inability to place a second guidewire into the distal
      true lumen and the other 4 were due to severe coronary calcification. Of these 4
      failures, 2 have final procedure success with the use of Rotablator and the
      remaining 2 patients were referred for bypass surgery. Major complication
      included severe coronary dissection that occurred in 1 (6.3%) patient, which was
      successfully treated by stenting. No other complications were observed.
      CONCLUSION: The wire-cutting technique may be considered as a simple and
      effective approach for facilitating balloon crossing resistant CTO lesions.

PMID- 22420422
TI  - The Gates Malaria Partnership: a consortium approach to malaria research and
      capacity development.
AB  - Recently, there has been a major increase in financial support for malaria
      control. Most of these funds have, appropriately, been spent on the tools needed
      for effective prevention and treatment of malaria such as insecticide-treated bed
      nets, indoor residual spraying and artemisinin combination therapy. There has
      been less investment in the training of the scientists from malaria-endemic
      countries needed to support these large and increasingly complex malaria control
      programmes, especially in Africa. In 2000, with support from the Bill & Melinda
      Gates Foundation, the Gates Malaria Partnership was established to support
      postgraduate training of African scientists wishing to pursue a career in malaria
      research. The programme had three research capacity development components: a PhD
      fellowship programme, a postdoctoral fellowship programme and a laboratory
      infrastructure programme. During an 8-year period, 36 African PhD students and
      six postdoctoral fellows were supported, and two research laboratories were built
      in Tanzania. Some of the lessons learnt during this project--such as the need to
      improve PhD supervision in African universities and to provide better support for
      postdoctoral fellows--are now being applied to a successor malaria research
      capacity development programme, the Malaria Capacity Development Consortium, and
      may be of interest to other groups involved in improving postgraduate training in
      health sciences in African universities.

PMID- 22420423
TI  - Low expression levels of ATM may substitute for CHEK2 /TP53 mutations predicting
      resistance towards anthracycline and mitomycin chemotherapy in breast cancer.
AB  - INTRODUCTION: Mutations affecting p53 or its upstream activator Chk2 are
      associated with resistance to DNA-damaging chemotherapy in breast cancer. ATM
      (Ataxia Telangiectasia Mutated protein) is the key activator of p53 and Chk2 in
      response to genotoxic stress. Here, we sought to evaluate ATM's potential role in
      resistance to chemotherapy. METHODS: We sequenced ATM and assessed gene
      expression levels in pre-treatment biopsies from 71 locally advanced breast
      cancers treated in the neoadjuvant setting with doxorubicin monotherapy or
      mitomycin combined with 5-fluorouracil. Findings were confirmed in a separate
      patient cohort treated with epirubicin monotherapy. Each tumor was previously
      analyzed for CHEK2 and TP53 mutation status. RESULTS: While ATM mutations were
      not associated with chemo-resistance, low ATM expression levels predicted chemo
      resistance among patients with tumors wild-type for TP53 and CHEK2 (P = 0.028).
      Analyzing the ATM-chk2-p53 cascade, low ATM levels (defined as the lower 5 to 50%
      percentiles) or mutations inactivating TP53 or CHEK2 robustly predicted
      anthracycline resistance (P-values varying between 0.001 and 0.027 depending on
      the percentile used to define "low" ATM levels). These results were confirmed in
      an independent cohort of 109 patients treated with epirubicin monotherapy. In
      contrast, ATM-levels were not suppressed in resistant tumors harboring TP53 or
      CHEK2 mutations (P > 0.5). CONCLUSIONS: Our data indicate loss of function of the
      ATM-Chk2-p53 cascade to be strongly associated with resistance to
      anthracycline/mitomycin-containing chemotherapy in breast cancer.

PMID- 22420424
TI  - Potential serodiagnostic markers for Q fever identified in Coxiella burnetii by
      immunoproteomic and protein microarray approaches.
AB  - BACKGROUND: Coxiella burnetii is the etiological agent of Q fever. The clinical
      diagnosis of Q fever is mainly based on several serological tests. These tests
      all need Coxiella organisms which are difficult and hazardous to culture and
      purify. RESULTS: An immunoproteomic study of C. burnetii Xinqiao strain isolated
      in China was conducted with the sera from experimentally infected BALB/c mice and
      Q fever patients. Twenty of whole proteins of Xinqiao recognized by the infection
      sera were identified by mass spectrometry. Nineteen of the 20 proteins were
      successfully expressed in Escherichia coli and used to fabricate a microarray
      which was probed with Q fever patient sera. As a result, GroEL, YbgF, RplL, Mip,
      OmpH, Com1, and Dnak were recognized as major seroreactive antigens. The major
      seroreactive proteins were fabricated in a small microarray and further analyzed
      with the sera of patients with rickettsial spotted fever, Legionella pneumonia or
      streptococcal pneumonia. In this analysis, these proteins showed fewer cross
      reactions with the tested sera. CONCLUSIONS: Our results demonstrate that these 7
      Coxiella proteins gave a modest sensitivity and specificity for recognizing of Q
      fever patient sera, suggesting that they are potential serodiagnostic markers for
      Q fever.

PMID- 22420425
TI  - Induction of immune tolerance in mice with a novel mucosal nanoemulsion adjuvant
      and self-antigen.
AB  - AIM: The aim of this study was to investigate the impact of a novel nanoemulsion
      (NE) adjuvant, a soybean oil emulsion, on autoimmune response. To this end, we
      used murine thyroglobulin (mTg)-induced experimental autoimmune thyroiditis in
      mice as a study model. MATERIALS & METHODS: Mice received NE or NE + mTg by nasal
      delivery. At 1 week after the second nasal delivery of NE with or without mTg,
      all mice were immunized with mTg and lipopolysaccharides to induce experimental
      autoimmune thyroiditis. RESULTS: Compared with controls, mTg-NE-treated mice had
      much more antigens accumulated in the nasal passage and thymus and developed a
      milder form of thyroiditis. This was accompanied by an increase in IL-10, IL-17
      and reduced IFN-gamma. The production of anti-mTg antibodies was significantly
      decreased in mTg-NE-treated mice. The percentage of Tregs in cervical lymph nodes
      was higher in mTg-NE-treated mice than NE-treated mice. Furthermore, Foxp3 and
      TGF-beta levels were prominently enhanced in mTg-NE-treated mice. CONCLUSION:
      This study indicates that a low dose of mTg in NE can significantly enhance
      antigen uptake and Tregs, resulting in inhibition of experimental autoimmune
      thyroiditis development.

PMID- 22420426
TI  - Clinical and molecular analysis of RASopathies in a group of Turkish patients.
AB  - The 'RASopathies' are a group of disorders sharing many clinical features and a
      common pathophysiology. In this study, we aimed to clinically evaluate a group of
      Turkish patients and elucidate the underlying genetic etiology. Thirty-one
      patients with a clinical diagnosis of one of the RASopathy syndromes were
      included in the study. Of these, 26 (83.8%) had a clinical diagnosis of Noonan
      syndrome, whereas 5 had a clinical diagnosis of either Costello, LEOPARD or
      cardio-facio-cutaneous syndromes. Twenty of 31 (64.5%) patients were found to be
      mutation positive. Mutations in PTPN11, SOS1 and SHOC2 genes were detected in
      patients with Noonan syndrome (57.6%). Mutations in MEK1, PTPN11, BRAF and HRAS
      genes were detected in the remaining. Pulmonary stenosis was the most common
      (61.5%) cardiac anomaly. Among Noonan syndrome patients with a confirmed
      mutation, mild intellectual disability tended to be more common in patients with
      PTPN11 mutation than in those with SOS1 mutation. Hematologic evaluation revealed
      coagulation defects in three Noonan syndrome patients with a mutation. This is
      currently the largest clinical and molecular study in Turkish RASopathy patients.
      Our findings indicate that molecular epidemiology and genotype-phenotype
      correlations in RASopathies are relatively independent from the ethnic population
      background.

PMID- 22420427
TI  - Highly efficient synthesis of N-substituted isoindolinones and phthalazinones
      using Pt nanowires as catalysts.
AB  - A series of N-substituted isoindolinones have been successfully synthesized
      through the reductive C-N coupling and intramolecular amidation of 2
      carboxybenzaldehyde and amines. This one-pot synthesis gives excellent yields
      using ultrathin Pt nanowires as catalysts under 1 bar of hydrogen. These
      unsupported catalysts can also be used for the synthesis of phthalazinones in
      high yield when hydrazine or phenyl hydrazine is used instead of amines.

PMID- 22420428
TI  - Chlorhexidine ototoxicity in ear surgery, part 1: review of the literature.
AB  - OBJECTIVE: Chlorhexidine is a common antiseptic used to prevent surgical
      infection. However, its exposure to the middle ear may lead to deafness. The
      mechanisms of the ototoxicity of chlorhexidine are reviewed. The importance of
      recognizing its toxicity cannot be overstated in preventing injury to patients
      undergoing ear surgery. METHODS: A systematic literature search was performed
      looking at data from human and animal studies. Search engines included MEDLINE,
      EMBASE, The Cochrane Library, CENTRAL, CINAHL, and Web of Science to November 1,
      2010, for relevant studies published in all languages. Two independent reviewers
      (P.L. and D.D.P.) screened the references from published articles for additional
      relevant studies. Medical Subject Headings and key words including intervention
      (chlorhexidine, antiseptic), exposure (myringoplasty, intratympanic), and adverse
      effects (sensorineural hearing loss, ototoxicity, vestibular toxicity) were used.
      RESULTS: Twelve studies were identified, two of which were non-English and were
      excluded. Only 2 articles on human subjects and 12 articles on animal models
      concerning chlorhexidine ototoxicity were identified. CONCLUSIONS: Chlorhexidine
      in both human studies and animal models demonstrates ototoxicity if it reaches
      the inner ear. The toxicity of chlorhexidine appears to be related to its
      concentration and probable contact time with the round window membrane
      intraoperatively. It is conceivable that the incidence of chlorhexidine toxicity
      may be higher than stated if unrecognized or has resulted in subsequent
      medicolegal actions. From the evidence available, safer preparation solutions are
      available without clinical risks for ototoxicity should surgeons continue with
      this practice.

PMID- 22420429
TI  - Chlorhexidine ototoxicity in ear surgery part II: survey of preparation solution
      used by otolaryngologists in Canada: is there a cause for concern?
AB  - OBJECTIVE: To conduct a survey of the antiseptic preparations used for ear
      surgeries among otolaryngologists in Canada. METHODS: An electronic survey was
      sent to active members of the Canadian Society of Otolaryngology-Head and Neck
      Surgery via e-mail. Questions included the use of antiseptic, choice of
      preparation solution, duration of preparation, use of a barrier method, and
      compliance with hospital protocol changes. RESULTS: The e-mail was received by
      253 otolaryngologists, and 85 completed the survey. Four of 85 respondents did
      not perform tympanoplasty surgery and were not included in the analysis. Of those
      who performed tympanoplasty (n  =  81), 78 of the 81 respondents (96%) used an
      antiseptic preparation solution at surgery, whereas 3 respondents (4%) did not.
      Sixty-six of the 77 respondents (86%) used aqueous povidone-iodine, 4 (5%) used a
      chlorhexidine-based preparation, 3 (4%) used an alcohol-based solution, 3 (4%)
      used others, and 1 answered "I don't know." Thirty-eight of 75 (29%) respondents
      used a barrier method, 23 (31%) answered "always," 18 (24%) answered "sometimes,"
      and 5 (7%) answered "I don't know." When asked if they would comply with a
      hypothetical hospital policy to use chlorhexidine in ear surgery, 15 of 79 (19%)
      respondents agreed, whereas 64 (81%) disagreed. Among the aqueous povidone-iodine
      users (n  =  66), 7 (11%) agreed to change to chlorhexidine. CONCLUSIONS: There
      is a wide variation in practice in the use of surgical preparation solution among
      otolaryngologists performing ear surgery. Surgeons must be vigilant to avoid
      ototoxicity. A national society consensus on appropriate preparation solutions
      for ear surgery would minimize patients' risk and minimize future medicolegal
      actions.

PMID- 22420430
TI  - Frequency perception and cell injury in the semicircular canal caused by
      gentamicin.
AB  - OBJECTIVE: The frequency characteristics of the vestibular organ have gained
      notice in recent years, but the morphologic basis was unknown. This study
      investigated the gentamicin-induced damage of frequency-selective perception of
      the horizontal semicircular canal and its morphologic basis. METHODS: Eighty
      guinea pigs were randomly divided into four groups, one control group and three
      experimental groups. The experimental animals received gentamicin subcutaneously
      for 1 to 3 weeks. Short-latency vestibular evoked potentials evoked by 0.5 and 10
      Hz step rotation stimuli following drug administration were recorded, and then
      the crista ampullaris of the horizontal semicircular canals was investigated by
      scanning and transmission electron microscopy. RESULTS: Damage to hair cells of
      the crista ampullaris is concentrated at the apex area first and then extends to
      the peripheral area of the vestibular crista ampullaris when the gentamicin
      administration time increased. When only the hair cells at the apex area are
      damaged, the high-frequency (10 Hz) rotation perception of the crista ampullaris
      of the horizontal semicircular canal was injured, but perceptions to 0.5 Hz step
      rotation stimulation remained normal. CONCLUSION: Gentamicin mainly affects the
      high-frequency perception function of the crista ampullaris of the horizontal
      semicircular canal. The hair cells at the central apex area of the crista
      ampullaris might be responsible for high-frequency rotation perception function.

PMID- 22420431
TI  - Discrepancy between ultrasound and final pathologic measurements in thyroid
      cancer.
AB  - BACKGROUND: The size of the malignancy in well-differentiated thyroid carcinoma
      (WDTC) is an important factor in patient risk stratification. Final pathologic
      measurements are currently used for treatment decisions. Measurements are made by
      both ultrasonography and on final pathology and should, theoretically, agree with
      each other. OBJECTIVE: To evaluate the agreement between ultrasound and final
      pathologic measurements in thyroid nodules and WDTC. METHODS: A retrospective
      chart review of all total thyroidectomies between 1998 and 2007 was completed by
      four different surgeons at one centre. Thyroid specimens with a solitary nodule
      and complete ultrasound and pathologic data were included. A comparison of
      discrepancy and concordance of the largest dimension of the nodule by ultrasound
      and pathologic measurement was made. RESULTS: A total of 263 thyroid specimens
      with a solitary nodule were identified. Of these, 68 were found to harbour WDTC.
      A median underestimation by pathology of 0.54 cm was present in WDTC, averaging
      20% of the nodule size by pathology. This trend was consistent with subgroup
      analysis for size, pathology, and nodularity. An underestimation by pathology of
      0.4 cm was present for papillary carcinoma under 1 cm. Grouping nodules by size,
      a concordance of 80% was present for nodules under 1 cm. Statistical testing
      revealed weak correlation and a kappa of approximately 0.3 for agreement.
      Weighted kappa was approximately 0.5 for agreement. CONCLUSION: The recent
      advances in ultrasonography and the constraints of pathology preparation allow an
      argument to be made for investigation of using ultrasound measurements as an
      adjunct in making treatment decisions.

PMID- 22420432
TI  - Outpatient thyroid surgery in a Toronto community hospital.
AB  - BACKGROUND: Thyroid surgery has been traditionally viewed as a procedure
      necessitating hospitalization of patients. There is a small but growing body of
      literature demonstrating the safety and efficacy of outpatient thyroid surgery.
      OBJECTIVES/DESIGN: Based on a review of the literature and a description of the
      protocol used to identify patients who are candidates for outpatient procedures,
      complications associated with the management of these patients are discussed.
      SETTING: Teritary referral otolaryngology practice within a community hospital.
      RESULTS: The study period included 247 thyroid surgeries, of which 94 were
      completed on an outpatient basis. No complications were identified in the
      outpatient group. CONCLUSIONS: Outpatient subtotal thyroidectomy is safe and
      effective. It has not been shown to increase postoperative complication rates.
      The practice of outpatient thyroid surgery can be of financial benefit to the
      Canadian health care system.

PMID- 22420433
TI  - Response rates for mailout survey-driven studies in patients waiting for thyroid
      surgery.
AB  - BACKGROUND: In the surgical literature, mailout survey studies are becoming more
      prevalent. The objective of this article is to summarize response rates in
      patients waiting for thyroid surgery and to document the methodology of mailout
      survey questionnaires. METHODS: The results reported here are from a study
      assessing clinical and sociodemographic factors associated with high levels of
      anxiety while patients are waiting for thyroid surgery. The surveys used in this
      study include a sociodemographic patient opinion questionnaire, the Hospital
      Anxiety Depression Scale (HADS), the Illness Intrusiveness Ratings Scale (IIRS),
      the Perceived Stress Scale (PSS), and the Impact of Events Scale-Revised (IES-R).
      A modified Dillman tailored design approach was used. Assessment of nonresponders
      was performed. RESULTS: The methods used yielded a response rate of 54% with this
      patient population. Some differences were noted among responders and
      nonresponders. CONCLUSION: This response rate is comparable to but in the lower
      spectrum of that stated in the oncology literature likely owing to the increase
      in the length of the survey, number of sensitive questions, limitations in the
      number of mailouts, and limited familiarity with the surgeon requesting
      participation in research.

PMID- 22420434
TI  - Cost-effectiveness of positron emission tomography/computed tomography in the
      management of advanced head and neck cancer.
AB  - BACKGROUND: Positron emission tomography/computed tomography (PET/CT) is a newer
      imaging modality that combines whole-body PET using [(18)F]fluorodeoxyglucose
      (FDG) and contrasted high-resolution CT. This has the advantage of combining the
      functional imaging of FDG-PET with the anatomic detail afforded by CT. OBJECTIVE:
      To assess the cost-benefit of whole-body PET/CT as a diagnostic tool in head and
      neck cancer. METHODS: A retrospective cohort (American Joint Committee on Cancer
      III-IVB squamous cell carcinoma in 2003) was reviewed for costs of diagnostic
      tests, distant metastases, and treatment type. This was compared to a
      hypothetical cohort of patients using PET/CT as a sole diagnostic tool using the
      current literature on test characteristics in the detection of distant
      metastases. The main outcome measure was the cost of the diagnostic workup, and
      the secondary outcome measure was the cost of the treatment. RESULTS: The cost of
      the traditional workup was $450 per patient, whereas the cost of PET/CT workup
      was $722 per patient. The sensitivity of the traditional workup for lung
      metastases at 12 months was 14.3%. The average cost of curative surgery was
      $81,290, radiotherapy was $8,224, and chemotherapy was $1,158. In the cohort of
      76 patients reviewed, improved PET/CT sensitivity would theoretically detect
      three more cases of metastatic disease and reduce the total cohort cost of
      treatment by $198,526 by relegating these patients to palliation. CONCLUSIONS:
      PET/CT is a more expensive test when used alone in the diagnostic workup of head
      and neck cancer but results in an overall cost savings by reducing the number of
      futile radical treatments. There is a cost benefit to the use of PET/CT as the
      diagnostic and staging test for head and neck cancer patients.

PMID- 22420435
TI  - Detailed analysis of graft techniques for nasal reconstruction following Wegener
      granulomatosis.
AB  - BACKGROUND: Saddle nose deformity secondary to Wegener granulomatosis (WG)
      presents a significant challenge for the reconstructive surgeon. Various grafting
      options have been proposed, but achieving good outcomes can be difficult.
      METHODS: We conducted a retrospective analysis of 10 patients with WG who
      underwent reconstruction of saddle nose deformities by the senior author (A.G.)
      between 2005 and 2009. All patients were reconstructed using costal cartilage
      grafts. RESULTS: Primary surgery was functionally and cosmetically successful in
      8 of 10 patients. Two patients experienced complications (graft resorption and
      columellar necrosis) requiring revision surgery; subsequently, they achieved good
      outcomes, with no further complications. There were no complications at the
      costal cartilage donor site. At the conclusion of the study, all patients were
      satisfied with their reconstructions. CONCLUSIONS: With a multidisciplinary team
      approach to pre- and postoperative patient management and careful surgical
      technique, reliable and excellent functional and cosmetic outcomes can be
      achieved with costal cartilage grafts.

PMID- 22420436
TI  - Novel outpatient approach to lower lip reanimation using a palmaris longus tendon
      sling.
AB  - OBJECTIVE: To report a new approach to lower lip reanimation, which can be
      performed in the outpatient clinic setting. STUDY DESIGN: Cross-sectional study.
      SETTING: Tertiary and quaternary care academic hospital, Toronto. SUBJECTS AND
      METHODS: An evaluation of nine patients with marginal mandibular nerve injury,
      who underwent harvest of the palmaris longus tendon and static suspension of the
      lower lip, was performed in the outpatient setting. Outcome measures included
      subjective self-evaluation of the functional and aesthetic results using the Lip
      Reanimation Outcomes Questionnaire and postoperative photographic grading of
      symmetry at rest and during three smile poses. Medical records were reviewed for
      demographics and complications. RESULTS: Seventy-eight percent of patients
      reported overall improvements in smiling, oral competence, and speech
      articulation following tendon transfer. Photographic grading by the judging panel
      found satisfactory smile symmetry postprocedure. CONCLUSIONS: The palmaris longus
      tendon sling procedure provides an effective, additional option for reanimation
      of the paralyzed lower lip.

PMID- 22420437
TI  - Sphenoid sinus septations: unpredictable anatomic landmarks in endoscopic
      pituitary surgery.
AB  - OBJECTIVE: We sought to determine whether sphenoid sinus septations could be used
      as predictable landmarks to identify the internal carotid artery prominence.
      METHODS: Fifty-six preoperative, high-resolution computed tomographic scans were
      identified between January 2007 and December 2009 on patients undergoing
      endoscopic transsphenoidal pituitary tumour resection. The number and termination
      locations of sphenoid sinus septations were noted, and their relationship to the
      internal carotid artery prominence was studied. RESULTS: In this series, each
      sphenoid sinus contained a mean of 1.57 septations. We analyzed 88 sphenoid sinus
      septations and found only 17% inserting at either internal carotid artery
      prominence. CONCLUSION: In our study, the presence of sphenoid sinus septations
      could not be reliably used as a surgical landmark to predict the location of the
      internal carotid artery. Our article stands in contrast to other literature on
      this topic.

PMID- 22420438
TI  - Changes in the ocular and nasal cultures in patients who had undergone
      septoplasty.
AB  - OBJECTIVE: The aim of the study was to evaluate the microbiologic changes that
      occurred in the nasal and ocular mucosa before and after surgery in patients who
      had undergone septoplasty. DESIGN SETTING: Fifty-five patients who applied to our
      clinic with septal deviation were included in the study. METHODS: Before and
      after the operation, samples were taken from the ocular and inner nasal mucosa
      for cultures and direct microscopic evaluation and the microbiologic changes were
      compared. MAIN OUTCOME MEASURES: The results of ocular preoperative cultures were
      different from the results of postoperative cultures. RESULTS: The most frequent
      microorganisms in all pre- and postoperative ocular and nasal cultures were
      similar; coagulase-negative Staphylococcus, Staphylococcus aureus, and
      Diphtheroid spp were dominant. Following septoplasty, the rate of determining
      microorganisms in the eye in both microscopic evaluation and cultures had
      increased. In the postoperative period, the rate of growing S. aureus increased
      in ocular cultures (p < .01) while remaining the same in nasal cultures.
      CONCLUSIONS: These results suggest that ocular flora can indeed change following
      septoplasty; however, the risk of ocular infection is not increased. This is the
      first study to investigate the risk of ocular infection in addition to local
      nasal infection after septoplasty.

PMID- 22420439
TI  - Role of nasopharyngeal reflux in the etiology of otitis media with effusion.
AB  - OBJECTIVES: To investigate nasopharyngeal reflux in children with otitis media
      with effusion (OME) using 24-hour dual-probe pH monitoring and to determine
      whether nasopharyngeal reflux has a role in the etiology of OME. METHODS: The
      study was performed in 20 children with OME and adenoid hypertrophy (+/-
      tonsillar hypertrophy) and in 20 controls who had adenoid hypertrophy (+/-
      tonsillar hypertrophy) without any ear problems. All subjects underwent 24-hour
      pH monitoring with a dual probe. The proximal probe was placed in the nasopharynx
      in this procedure. RESULTS: In the study group, 25% (5 of 20) of the patients
      were found to have nasopharyngeal reflux and 30% (6 of 20) of them were found to
      have esophageal reflux. On the other hand, nasopharyngeal reflux was detected in
      3 (15%) of 20 children in the control group, whereas esophageal reflux was
      detected in 3 (15%) of them. When the groups were compared for the incidence of
      nasopharyngeal reflux and esophageal reflux, the difference was not found to be
      statistically significant (p > .05). CONCLUSIONS: We detected higher
      nasopharyngeal and esophageal reflux rates in the OME group, although the
      difference between the groups studied was not statistically significant. This
      issue must be addressed in new studies performed in larger series.

PMID- 22420444
TI  - Histoplasma rhinosinusitis presenting as a nonhealing oral ulcer in an
      immunocompetent patient.

PMID- 22420445
TI  - Stuttering after adenotonsillectomy and ventilation tube insertion.

PMID- 22420446
TI  - Genetic trade-offs and conditional neutrality contribute to local adaptation.
AB  - Divergent natural selection promotes local adaptation and can lead to
      reproductive isolation of populations in contrasting environments; however, the
      genetic basis of local adaptation remains largely unresolved in natural
      populations. Local adaptation might result from antagonistic pleiotropy, where
      alternate alleles are favoured in distinct habitats, and polymorphism is
      maintained by selection. Alternatively, under conditional neutrality some alleles
      may be favoured in one environment but neutral at other locations. Antagonistic
      pleiotropy maintains genetic variation across the landscape; however, there is a
      systematic bias against discovery of antagonistic pleiotropy because the fitness
      benefits of local alleles need to be significant in at least two environments.
      Here, we develop a generally applicable method to investigate polygenic local
      adaptation and identify loci that are the targets of selection. This approach
      evaluates allele frequency changes after selection at loci across the genome to
      distinguish antagonistic pleiotropy from conditional neutrality and deleterious
      variation. We investigate local adaptation at the qualitative trait loci (QTL)
      level in field experiments, in which we expose 177 F(6) recombinant inbred lines
      and parental lines of Boechera stricta (Brassicaceae) to their parental
      environments over two seasons. We demonstrate polygenic selection for native
      alleles in both environments, with 2.8% of the genome exhibiting antagonistic
      pleiotropy and 8% displaying conditional neutrality. Our study strongly supports
      antagonistic pleiotropy at one large-effect flowering phenology QTL (nFT): native
      homozygotes had significantly greater probabilities of flowering than foreign
      homozygotes in both parental environments. Such large-scale field studies are
      essential to elucidate the genetic basis of adaptation in natural populations.

PMID- 22420447
TI  - The problematization of medical tourism: a critique of neoliberalism.
AB  - The past two decades have seen the extensive privatisation and marketisation of
      health care in an ever reaching number of developing countries. Within this
      milieu, medical tourism is being promoted as a rational economic development
      strategy for some developing nations, and a makeshift solution to the escalating
      waiting lists and exorbitant costs of health care in developed nations. This
      paper explores the need to problematize medical tourism in order to move beyond
      one dimensional neoliberal discourses that have, to date, dominated the arena. In
      this problematization, the paper discusses a range of understandings and uses of
      the term 'medical tourism' and situates it within the context of the neoliberal
      economic development of health care internationally. Drawing on theory from
      critical medical anthropology and health and human rights perspectives, the paper
      critically analyzes the assumed independence between the medical tourism industry
      and local populations facing critical health issues, where social, cultural and
      economic inequities are widening in terms of access, cost and quality of health
      care. Finally, medical tourism is examined in the local context of India,
      critiquing the increasingly indistinct roles played by government and private
      sectors, whilst linking these shifts to global market forces.

PMID- 22420448
TI  - How to regulate medical tourism (and why it matters for bioethics).
AB  - A growing literature examines descriptive and normative questions about medical
      tourism such as: How does it operate? What are its effects? Are home country
      patients or their governments failing in moral duties by engaging in or
      permitting medical tourism? By contrast, much less has been written on the
      regulatory dimension: What might be done about medical tourism if we were
      convinced that it posed ethical issues and were motivated to act? I shall argue
      that this kind of regulatory analysis is essential for bioethical analysis of
      medical tourism. This article focuses on these regulatory questions more
      directly, evaluating available methods, restrictions, costs, and benefits of home
      and destination country unilateral regulatory moves. This article also discusses
      more briefly multilateral treaty and private sector responses.

PMID- 22420449
TI  - News media reports of patient deaths following 'medical tourism' for cosmetic
      surgery and bariatric surgery.
AB  - Contemporary scholarship examining clinical outcomes in medical travel for
      cosmetic surgery identifies cases in which patients traveled abroad for medical
      procedures and subsequently returned home with infections and other surgical
      complications. Though there are peer-reviewed articles identifying patient deaths
      in cases where patients traveled abroad for commercial kidney transplantation or
      stem cell injections, no scholarly publications document deaths of patients who
      traveled abroad for cosmetic surgery or bariatric surgery. Drawing upon news
      media reports extending from 1993 to 2011, this article identifies and describes
      twenty-six reported cases of deaths of individuals who traveled abroad for
      cosmetic surgery or bariatric surgery. Over half of the reported deaths occurred
      in two countries. Analysis of these news reports cannot be used to make causal
      claims about why the patients died. In addition, cases identified in news media
      accounts do not provide a basis for establishing the relative risk of traveling
      abroad for care instead of seeking elective cosmetic surgery at domestic health
      care facilities. Acknowledging these limitations, the case reports suggest the
      possibility that contemporary peer-reviewed scholarship is underreporting patient
      mortality in medical travel. The paper makes a strong case for promoting
      normative analyses and empirical studies of medical travel. In particular, the
      paper argues that empirically informed ethical analysis of 'medical tourism' will
      benefit from rigorous studies tracking global flows of medical travelers and the
      clinical outcomes they experience. The paper contains practical recommendations
      intended to promote debate concerning how to promote patient safety and quality
      of care in medical travel.

PMID- 22420450
TI  - Stem cell tourism and future stem cell tourists: policy and ethical implications.
AB  - Stem cell tourism is a small but growing part of the thriving global medical
      tourism marketplace. Much stem cell research remains at the experimental stage,
      with clinical trials still uncommon. However, there are over 700 clinics
      estimated to be operating in mostly developing countries--from Costa Rica and
      Argentina to China, India and Russia--that have lured many patients, mostly from
      industrialized countries, driven by desperation and hope, which in turn continue
      to fuel the growth of such tourism. While much research has focused on such
      dimensions as the promotions that allow such businesses to make their services
      known, media coverage, some patient research, and regulatory conditions for
      developing country clinics, little attention has been paid to the non-affected
      members of the general population, the future potential users of such services.
      This empirical study based on five focus group discussions with a diverse group
      of healthy adults in a Canadian city, explored participant views of patients who
      use stem cell tourism services, the likelihood they would avail themselves of
      such services if they were to suffer similar illnesses, and the conditions under
      which they might do so, and the impact that admonitions and advice from
      international expert bodies might have on their decisions. Our findings suggest
      that these healthy adults are sympathetic to the drivers of hope and desperation,
      and, despite cautions about research limitations, may seek such treatments
      themselves under similar conditions. These findings are discussed in the context
      of the policy and ethical issues raised by this form of medical tourism.

PMID- 22420451
TI  - How to address the ethics of reproductive travel to developing countries: a
      comparison of national self-sufficiency and regulated market approaches.
AB  - One of the areas of concern raised by cross-border reproductive travel regards
      the treatment of women who are solicited to provide their ova or surrogacy
      services to foreign consumers. This is particularly troublesome in the context of
      developing countries where endemic poverty and low standards for both medical
      care and informed consent may place these women at risk of exploitation and harm.
      We explore two contrasting proposals for policy development regarding the
      industry, both of which seek to promote ethical outcomes and social justice:
      While one proposal advocates efforts to minimize cross-border demand for female
      reproductive resources through the pursuit of national self-sufficiency, the
      other defends cross-border trade as a means for meeting the needs of vulnerable
      groups. Despite the conflicting objectives of the proposed strategies, the paper
      identifies common values and points of agreement between the two, including the
      importance of regulations to safeguard those providing ova or surrogacy services.

PMID- 22420452
TI  - New ethical perspectives on medical tourism in the developing world.

PMID- 22420453
TI  - Effects of concurrent intravenous morphine sulfate and naltrexone hydrochloride
      on end-tidal carbon dioxide.
AB  - BACKGROUND: Respiratory depression, a potentially fatal side-effect of opioid
      overdose, may be reversed by timely administration of an opioid antagonist, such
      as naloxone or naltrexone. Tampering with a formulation of morphine sulfate and
      sequestered naltrexone hydrochloride extended release capsules (MS-sNT) releases
      both the opioid morphine and the antagonist naltrexone. A study in recreational
      opioid-users indicated that morphine and naltrexone injected in the 25:1 ratio
      (duplicating the ratio of the formulation) found MS-sNT reduced morphine-induced
      euphoric effects vs intravenous (IV) morphine alone. In the same study, the
      effects of morphine + naltrexone on end-tidal carbon dioxide (EtCO2), a measure
      of respiratory-depression, were evaluated and these data are reported here.
      METHODS: Single-center, placebo-controlled, double-blind crossover study. Non
      dependent male opioid users were randomized to receive single IV doses of
      placebo, 30 mg morphine alone, and 30 mg morphine + 1.2 mg naltrexone. EtCO2 was
      measured by noninvasive capnography. RESULTS: Significant differences in EtCO2
      least-squares means across all treatments for maximal effect (Emax) and area
      under the effect curve (AUE0-2, AUE0-8, AUE0-24) were detected (all p <= 0.0011).
      EtCO2 Emax values for morphine + naltrexone were significantly reduced vs
      morphine alone (42.9 mm Hg vs 47.1 mm Hg, p < 0.0001) and were not significantly
      different vs placebo (41.9 mm Hg). Median time to reach maximal effect (TEmax)
      was delayed for morphine + naltrexone vs morphine alone (5.0 h vs 1.0 h).
      CONCLUSIONS: Results provide preliminary evidence that the naltrexone:morphine
      ratio within MS-sNT is sufficient to significantly reduce EtCO2 when administered
      intravenously to non-dependent male recreational opioid-users. Further studies
      with multiple measures of respiratory-function are warranted to determine if risk
      of respiratory depression is also reduced by naltrexone in the tampered
      formulation.

PMID- 22420454
TI  - Anion photoelectron spectra and ab initio calculations of the iodide-carbon
      monoxide clusters: I(-)...(CO)(n), n = 1-4.
AB  - Anion photoelectron spectra are reported for the iodide-carbon monoxide clusters,
      with supporting ab initio calculations for the 1:1 dimer anion and neutral
      complexes. A C(s) minimum geometry is predicted for the anion complex, while for
      the neutral complex two linear van der Waals minima are predicted differing in
      the attachment point of the iodine, that is, I...CO and I...OC. The predicted
      adiabatic photodetachment energy agrees well with the experimental spectrum. The
      photoelectron spectra feature a vibrational progression in the CO stretching
      mode, which becomes more pronounced for the larger clusters.

PMID- 22420455
TI  - Striving for success or addiction? Exercise dependence among elite Australian
      athletes.
AB  - Exercise dependence is a condition that involves a preoccupation and involvement
      with training and exercise, and has serious health and performance consequences
      for athletes. We examined the validity of a biopsychosocial model to explain the
      development and maintenance of exercise dependence among elite Australian
      athletes. Participants were 234 elite Australian athletes recruited from
      institutes and academies of sport. Thirty-four percent of elite athletes were
      classified as having exercise dependence based on high scores on the measure of
      exercise dependence. These athletes had a higher body mass index, and more
      extreme and maladaptive exercise beliefs compared to non-dependent athletes. They
      also reported higher pressure from coaches and teammates, and lower social
      support, compared to athletes who were not exercise dependent. These results
      support the utility of a biopsychosocial model of exercise dependence in
      understanding the aetiology of exercise dependence among elite athletes.
      Limitations of the study and future research directions are highlighted.

PMID- 22420456
TI  - Molecular and clinicopathological analysis of Epstein-Barr virus-associated
      posttransplant smooth muscle tumors.
AB  - Epstein-Barr virus (EBV)-associated posttransplant smooth muscle tumors (PTSMT)
      are very rare complications. We aimed to provide a clinicopathological
      characterization which is based on our own case series (n = 5) as well as
      previously reported PTSMT cases (n = 63). Meta-analysis of PTSMT and molecular
      analysis of tumor cells from our cohort was performed. Most PTSMT developed in
      kidney-transplanted patients (n = 41/68, 60%). Liver/transplant liver was the
      main site of manifestation (n = 38/68, 56%). Tumors occurred after a median
      interval of 48 months (range 5-348) and developed earlier in children than in
      adults. Most tumors showed no marked cellular atypia, low mitosis rate and no
      tumor necrosis. Gene expression analysis of 20 EBV-related genes, including two
      microRNAs, revealed overexpression of MYC (p = 0.0357). Therapy was mainly based
      on surgical resection or reduced immunosuppression but no significant differences
      in overall survival were evident. Lower overall survival was associated with
      multiorgan involvement (n = 33/68, 48.5%) and particularly with intracranial
      PTSMT manifestation (n = 7/68, 10%; p < 0.02), but not transplant involvement (n
      = 11/68, 16%). In summary, PTSMT differ from conventional leiomyosarcomas by
      their lack of marked atypia, unusual sites of involvement and defining EBV
      association. Surgery and reduced immunosuppression show comparable clinical
      results and prognosis is associated with intracranial manifestation.

PMID- 22420457
TI  - Save trees and toner: laminate!

PMID- 22420458
TI  - Cronobacter species (formerly known as Enterobacter sakazakii) in powdered infant
      formula: a review of our current understanding of the biology of this bacterium.
AB  - Cronobacter species (formerly known as Enterobacter sakazakii) are opportunistic
      pathogens that can cause necrotizing enterocolitis, bacteraemia and meningitis,
      predominantly in neonates. Infection in these vulnerable infants has been linked
      to the consumption of contaminated powdered infant formula (PIF). Considerable
      research has been undertaken on this organism in the past number of years which
      has enhanced our understanding of this neonatal pathogen leading to improvements
      in its control within the PIF production environment. The taxonomy of the
      organism resulted in the recognition of a new genus, Cronobacter, which consists
      of seven species. This paper presents an up-to-date review of our current
      knowledge of Cronobacter species. Taxonomy, genome sequencing, current detection
      protocols and epidemiology are all discussed. In addition, consideration is given
      to the control of this organism in the manufacturing environment, as a first step
      towards reducing the occurrence of this pathogen in PIF.

PMID- 22420459
TI  - Development cooperation for health: reviewing a dynamic concept in a complex
      global aid environment.
AB  - The 4th High Level Forum on Aid Effectiveness, held in Busan, South Korea in
      November 2011 again promised an opportunity for a "new consensus on development
      cooperation" to emerge. This paper reviews the recent evolution of the concept of
      coordination for development assistance in health as the basis from which to
      understand current discourses. The paper reviews peer-reviewed scientific
      literature and relevant 'grey' literature, revisiting landmark publications and
      influential authors, examining the transitions in the conceptualisation of
      coordination, and the related changes in development assistance. Four distinct
      transitions in the understanding, orientation and application of coordination
      have been identified: coordination within the sector, involving geographical
      zoning, sub-sector specialisation, donor consortia, project co-financing, sector
      aid, harmonisation of procedures, ear-marked budgetary support, donor agency
      reform and inter-agency intelligence gathering; sector-wide coordination,
      expressed particularly through the Sector-Wide Approach; coordination across
      sectors at national level, expressed in the evolution of Poverty Strategy
      Reduction Papers and the national monitoring of the Millennium Development Goals;
      and, most recently, global-level coordination, embodied in the Paris Principles,
      and the emergence of agencies such as the International Health Partnerships Plus.
      The transitions are largely but not strictly chronological, and each draws on
      earlier elements, in ways that are redefined in the new context. With the
      increasing complexity of both the territory of global health and its governance,
      and increasing stakeholders and networks, current imaginings of coordination are
      again being challenged. The High Level Forum in Busan may have been successful in
      recognising a much more complex landscape for development than previously
      conceived, but the challenges to coordination remain.

PMID- 22420461
TI  - Plastic's polluted burden: ES&T's top policy analysis article 2011.

PMID- 22420462
TI  - Improvement of anemia with decreasing hepcidin levels following valve replacement
      for severe tricuspid regurgitation.

PMID- 22420463
TI  - Copper-catalyzed asymmetric 1,4-addition of alkenyl alanes to N-substituted-2-3
      dehydro-4-piperidones.
AB  - Readily available vinyl alanes are used in the Cu-catalyzed asymmetric conjugate
      addition reaction to N-substituted-2-3-dehydro-4-piperidones. The enhanced
      reactivity of recently developed and easily prepared phosphine amine ligands in
      combination with inexpensive Cu(II)naphtenate (CuNp) allows the introduction of a
      great variety of alkenyl, alkyl, and aryl aluminums in high enantioselectivity.

PMID- 22420464
TI  - Patients' experiences of homecare nursing: balancing the duality between
      obtaining care and to maintain dignity and self-determination.
AB  - The aim of this study was to describe patients' experiences and perceptions of
      receiving nursing care in their private homes. A home is a place of security,
      independence and an arena for one's own routines. When nurses enter a patient's
      home, there are expectations from both sides which affect the social interaction.
      Maintaining patients' dignity demands that the nurse gets to know the patients
      and shows respect for their autonomy and integrity. A qualitative research method
      was chosen. Twenty-one patients with homecare nursing were interviewed in open
      interviews during 2008. Data were analysed according to the principles of
      interpretive description. The results are described in terms of three main
      themes: to be a person, to have trust and to have self-esteem. Patients reported
      experiencing certain events that could pose threats to their dignity, integrity
      and autonomy, as well as to their trust in nursing care. Patients have to deal
      with this ambiguity of accepting care while simultaneously maintaining
      independence and privacy. The nurses were perceived not as a guest but as
      professionals who would carry out a task in the interest of the patient. For
      patients, there is a duality in receiving homecare nursing and still exerting
      independence and self-determination in their homes. The patients developed
      strategies to balance their own privacy and dignity, despite the inconveniences
      the nursing treatment and procedures involved. This empowered them in their
      relationship with the professional caregivers.

PMID- 22420465
TI  - Myelin basic protein undergoes a broader range of modifications in mammals than
      in lower vertebrates.
AB  - Myelin basic protein (MBP) is an important component of the myelin sheath
      surrounding neurons, and it is directly affected in demyelinating diseases. MBP
      contains a relatively large number of post-translational modifications (PTMs),
      which have been reported to play a role in multiple sclerosis, while MBPs from
      lower vertebrates have been reported to be incapable of inducing multiple
      sclerosis or allergic encephalitis. This study reveals the extent of differences
      in PTM patterns for mammalian and nonmammalian MBPs. This included intact mass
      and de novo sequence analysis of approximately 85% of rattlesnake MBP, the first
      reptile MBP to be characterized, and of bovine MBP. We identified 12 PTMs at 11
      sites in the five bovine MBP charge components, which include both previously
      reported and novel modifications. The most notable modification is an acetylation
      of lysine 121. Other modifications found in bovine MBP include N-terminal
      acetylation in components C1, C2, and C3; oxidation of methionine 19 in all five
      components; all charge isomers having both a mono- and dimethylated (symmetric)
      arginine at position 106; deimination in arginines 23 and 47 found only in
      component C8b; deimination of arginine 96 and deamidation in glutamine 102 found
      in components C2, C3, C8a, and C8b; phosphorylation in threonine 97 restricted to
      charge components C2 and C3; deimination in arginine 161 only found in component
      C3; deamidation of glutamine 120 was only observed in C3. All four deiminated
      arginines and one acetylated lysine were first experimentally revealed in this
      study for bovine MBP. Mascot database searching combined with de novo sequence
      analysis of rattlesnake MBP provided more than 85% sequence coverage. A few PTMs
      were also revealed in rattlesnake MBP: mono- and dimethylated Arg, protein N
      terminal acetylation, and deiminated Arg. Overall, snake MBP was found to undergo
      less modification than bovine MBP on the basis of the mass heterogeneity of the
      intact protein, the bottom-up structure analysis, and the limited complexity of
      rattlesnake MBP chromatography. The combined data from this study and information
      from previous studies extend the known MBP PTMs, and PTMs unique to higher
      vertebrates are proposed.

PMID- 22420466
TI  - Wake-up times following sedation with sevoflurane versus propofol after cardiac
      surgery.
AB  - OBJECTIVES: Intravenous sedation in the intensive care unit (ICU) may contribute
      to altered consciousness and prolonged mechanical ventilation. We tested the
      hypothesis that replacing intravenous propofol with inhaled sevoflurane for
      sedation after cardiac surgery would lead to shorter wake-up times, quicker
      patient cooperation, and less delusional memories. DESIGN: Following coronary
      artery bypass surgery with cardiopulmonary bypass, 100 patients were randomized
      to sedation with sevoflurane via the anesthetic conserving device or propofol.
      Study drugs were administered for a minimum of 2 hours until criteria for
      extubation were met. Primary endpoints were time from drug stop to extubation and
      to adequate verbal response. Secondary endpoints were adverse recovery events,
      memories reported in the ICU Memory Tool test, and ICU/hospital stay. RESULTS:
      Median time from drug stop to extubation (interquartile range/total range) was
      shorter after sevoflurane compared to propofol sedation; 10 (10/100) minutes
      versus 25 (21/240) minutes (p <0.001). Time from extubation to adequate verbal
      response was shorter (p =0.036). No differences were found in secondary
      endpoints. CONCLUSIONS: Sevoflurane sedation after cardiac surgery leads to
      shorter wake-up times and quicker cooperation compared to propofol. No
      differences were seen in ICU-stay, adverse memories or recovery events in our
      short-term sedation.

PMID- 22420467
TI  - Gender and line size factors modulate the deviations of the subjective visual
      vertical induced by head tilt.
AB  - BACKGROUND: The subjective visual vertical (SVV, the visual estimation of
      gravitational direction) is commonly considered as an indicator of the sense of
      orientation. The present study examined the impact of two methodological factors
      (the angle size of the stimulus and the participant's gender) on deviations of
      the SVV caused by head tilt. Forty healthy participants (20 men and 20 women)
      were asked to make visual vertical adjustments of a light bar with their head
      held vertically or roll-tilted by 30 degrees  to the left or to the right. Line
      angle sizes of 0.95 degrees  and 18.92 degrees  were presented. RESULTS: The SVV
      tended to move in the direction of head tilt in women but away from the direction
      of head tilt in men. Moreover, the head-tilt effect was also modulated by the
      stimulus' angle size. The large angle size led to deviations in the direction of
      head-tilt, whereas the small angle size had the opposite effect. CONCLUSIONS: Our
      results showed that gender and line angle size have an impact on the evaluation
      of the SVV. These findings must be taken into account in the growing body of
      research that uses the SVV paradigm in disease settings. Moreover, this
      methodological issue may explain (at least in part) the discrepancies found in
      the literature on the head-tilt effect.

PMID- 22420468
TI  - Impact of self-rated osteoarthritis severity in an employed population: cross
      sectional analysis of data from the national health and wellness survey.
AB  - BACKGROUND: Although osteoarthritis (OA) often affects older persons, it has a
      profound effect on individuals actively employed. Despite reports of reduced
      productivity among workers with OA, data are limited regarding the impact of OA
      among workers. The objective of this study was to evaluate the impact of self
      rated OA severity on quality of life, healthcare resource utilization,
      productivity and costs in an employed population relative to employed individuals
      without OA. METHODS: This cross-sectional analysis used data derived from the
      2009 National Health and Wellness Survey (NHWS). Multivariable analyses
      characterized outcomes and costs (direct medical costs and indirect) among
      workers (full-time, part-time, or self-employed) >= 20 years of age who were
      diagnosed with OA and who self-rated their OA severity as mild, moderate, or
      severe relative to workers without OA. Evaluated outcomes included productivity,
      assessed using the Work Productivity and Impairment (WPAI) scale; health-related
      quality of life, using the SF-12v2 Health Survey; and healthcare resource
      utilization. RESULTS: 4,876 workers reported being diagnosed with OA (45.0% mild,
      45.9% moderate, and 9.1% severe); 34,896 workers comprised the non-OA comparator
      cohort. There was a greater proportion of females in the OA cohort (55.5% vs
      45.6%; P < 0.0001) and more individuals in the 40-64 year and >= 65 year age
      ranges (P < 0.0001). As OA severity increased, workers reported more frequent
      pain, poorer quality of life, greater use of specific healthcare resources
      (hospitalizations) and reduced productivity. All outcomes indicated a
      significantly greater burden among workers with OA relative to those without OA
      (P < 0.0001). Estimated total annual costs per worker were $9,801 for mild OA,
      $14,761 for moderate OA, $22,111 for severe OA compared with $7,901 for workers
      without OA (P < 0.0001). CONCLUSIONS: Workers with OA were characterized by
      significant disease and economic burdens relative to workers without OA that
      substantially increased with greater self-rated OA severity. Greater levels of OA
      severity were associated with reductions in quality of life and productivity, and
      increases in healthcare resource utilization and costs.

PMID- 22420469
TI  - The relationship between performances on neuropsychological symptom validity
      testing and the MCMI-III in patients with fibromyalgia.
AB  - Fibromyalgia is a disorder that frequently presents with both cognitive
      complaints and psychiatric symptoms. This study investigated the association
      between Symptom Validity Test (SVT) performance and psychiatric symptoms as
      measured by the Millon Clinical Multiaxial Inventory-III (MCMI-III), a common
      measure of psychopathology. A total of 72 fibromyalgia patients at a tertiary
      care clinic completed the MCMI-III, an embedded cognitive symptom validity test
      (Reliable Digit Span), and a stand-alone cognitive symptom validity test (the
      Word Memory Test or Test of Memory Malingering). Of these patients, 21% failed a
      stand-alone SVT, whereas an additional 15% failed both a stand-alone and embedded
      SVT. Individuals who failed both stand-alone and embedded cognitive SVTs had
      higher scores on a number of MCMI-III personality subscales and had elevated
      scores on MCMI-III modifying indices compared to individuals who passed cognitive
      SVTs. Moreover, SVT performance was significantly correlated with multiple MCMI
      III scores, including modifying indices, as well as the somatoform, depression,
      and anxiety subscales. In sum, cognitive and psychological symptom validity
      scores were significantly related. Given the new emphasis on cognitive complaints
      as part of the fibromyalgia diagnostic criteria, neuropsychological evaluation of
      both cognitive and psychological symptom validity should be a part of a
      comprehensive diagnostic assessment.

PMID- 22420470
TI  - Transition metal surface passivation induced graphene edge reconstruction.
AB  - In vacuum, the bare zigzag (zz) edge of graphene is reconstructed into a line of
      pentagon-heptagon pairs, while the pristine armchair (ac) edge is retained. Our
      first-principle explorations of graphene edges on three metal surfaces [Cu(111),
      Co(111), and Ni(111)] indicate an opposite tendency, that is, the pristine zz
      edge is energetically favorable and the reconstructed ac edge with dangling C
      atoms is highly stable on Co(111) and Ni(111) surfaces. Insightful analysis shows
      that passivation of the graphene edge by metal surfaces is responsible for the
      dramatic differences. Beyond this, the unique edge configuration has a
      significant impact on the graphene CVD growth behavior.

PMID- 22420472
TI  - New developments in tools for periodontal diagnosis.
AB  - OBJECTIVES: For decades there has been increasing focus on the development of
      clinically acceptable, more sensitive and specific methods for the accurate and
      non-invasive diagnosis and prognosis of periodontitis. There are several well
      known inherent drawbacks to current clinical procedures. The purpose of this
      article is to summarise some of the newly emerging diagnostic approaches, namely:
      the ultrasonographic probe; cone-beam computed tomography; optical coherence
      tomography; optical spectroscopy, and proteome analysis. RESULTS: These novel
      diagnostic tools complement one another and, together with conventional clinical
      and radiographic examination, are likely to provide more accurate methods of
      diagnosing periodontitis. However, these techniques are yet to be clinically
      validated and their potential interpreted. CONCLUSIONS: For the clinician, the
      planning of therapy is probably the most critical and difficult step in the
      treatment of patients with periodontal disease. A new paradigm for periodontal
      diagnosis will certainly increase understanding of periodontal diseases, which
      may eventually optimise the predictability of treatment and improve the clinical
      management of patients with periodontal disease.

PMID- 22420471
TI  - CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in
      basal-like breast cancer.
AB  - INTRODUCTION: Tumor infiltrating lymphocytes may indicate an immune response to
      cancer development, but their significance remains controversial in breast
      cancer. We conducted this study to assess CD8+ (cytotoxic T) lymphocyte
      infiltration in a large cohort of invasive early stage breast cancers, and to
      evaluate its prognostic effect in different breast cancer intrinsic subtypes.
      METHODS: Immunohistochemistry for CD8 staining was performed on tissue
      microarrays from 3992 breast cancer patients. CD8+ tumor infiltrating lymphocytes
      were counted as intratumoral when in direct contact with tumor cells, and as
      stromal in adjacent locations. Kaplan-Meier functions and Cox proportional
      hazards regression models were applied to examine the associations between tumor
      infiltrating lymphocytes and breast cancer specific survival. RESULTS: Among 3403
      cases for which immunohistochemical results were obtained, CD8+ tumor
      infiltrating lymphocytes were identified in an intratumoral pattern in 32% and
      stromal pattern in 61% of the cases. In the whole cohort, the presence of
      intratumoral tumor-infiltrating lymphocytes was significantly correlated with
      young age, high grade, estrogen receptor negativity, human epidermal growth
      factor receptor-2 positivity and core basal intrinsic subtype, and was associated
      with superior breast cancer specific survival. Multivariate analysis indicated
      that the favorable prognostic effect of CD8+ tumor infiltrating lymphocytes was
      significant only in the core basal intrinsic subgroup (Hazard ratio, HR = 0.35,
      95% CI = 0.23-0.54). No association with improved survival was present in those
      triple negative breast cancers that lack expression of basal markers (HR = 0.99,
      95% CI = 0.48-2.04) nor in the other intrinsic subtypes. CONCLUSIONS: CD8+ tumor
      infiltrating lymphocytes are an independent prognostic factor associated with
      better patient survival in basal-like breast cancer, but not in non-basal triple
      negative breast cancers nor in other intrinsic molecular subtypes.

PMID- 22420473
TI  - Dental composite fillings and bisphenol A among children: a survey in South
      Korea.
AB  - AIMS: Bisphenol A (BPA)-based dental composites have commonly been used to fill
      dental cavities or seal pits and fissures on teeth. However, epidemiological
      evidence with regard to the BPA exposure from dental composites among children
      has rarely been reported. This study investigated whether there is a relationship
      between the BPA concentration in urine and the presence of composite restorations
      and sealants among South Korean children. METHODS: Oral examinations and urine
      sample analyses were conducted on a total of 495 children aged 8-9 years. We
      classified the participants into four groups by the number of resin composites
      and sealant surfaces (0, 1-5, 6-10 and 11+). RESULTS: BPA concentrations in urine
      were higher in children with 11 or more surfaces restored with sealants and resin
      composites than in those with zero restored surfaces, although no difference was
      seen in the group with 1-10 surfaces. After adjusting for gender and age, the
      urinary BPA concentration in children with 11 or more resin composite surfaces
      was 2.67 MUg/g creatinine, which was higher than the concentration found in those
      with no filling surfaces (P < 0.01). CONCLUSIONS: Having many dental composite
      filling surfaces on teeth may increase the urinary BPA concentration in children.

PMID- 22420474
TI  - Antibacterial activity of a new mineral trioxide aggregate-based root canal
      sealer.
AB  - OBJECTIVES: To compare the antibacterial effect of AH-26, white-coloured mineral
      trioxide aggregate (WMTA) and CPM sealer against Staphylococcus aureus and
      Streptococcus mutans after 24 h and 1 week. MATERIALS AND METHODS: All materials
      were prepared according to the manufacturers' directions immediately before
      testing. The antibacterial effect of each agent was determined by measuring the
      diameter of the zone of inhibition in millimetres after incubation at 37 degrees
      C for 24 h and 7 days in a humid atmosphere. Each test was repeated three times.
      RESULTS: In the 24-h and 7-day samples, the antibacterial activity of AH-26 was
      significantly greater than that of the two other materials tested against both
      bacteria (P < 0.05). The antibacterial activities of CPM sealer and WMTA against
      S. aureus were not significantly different (P > 0.05) in 24-h or 7-day samples,
      but CPM sealer demonstrated a significantly greater effect than WMTA against S.
      mutans (P < 0.05). CONCLUSION: All products studied exhibited antibacterial
      activity. However, in 24-h and 7-day samples, AH-26 exerted the greatest activity
      against both organisms tested.

PMID- 22420475
TI  - Efficacy comparison of periapical infiltration injection of dexamethasone,
      morphine and placebo for postoperative endodontic pain.
AB  - OBJECTIVE: To evaluate the efficacy of periapical infiltration injection of
      dexamethasone and morphine in reducing postoperative endodontic pain. METHOD:
      Ninety patients participated in this double-blind randomised controlled clinical
      trial. They were referred to the dental school of Shahid Beheshti Medical
      University, Tehran, Iran for conventional endodontic treatment of molar teeth.
      The canals of each tooth were completely prepared with cleansing and shaping. The
      patients were randomly divided into three experimental groups to receive
      dexamethasone, morphine or normal saline (1 mL). Patients were then instructed to
      complete a pain diary 4, 8, 24 and 48 h after the appointment. Statistical
      analysis consisted of chi-squared test, analysis of variance and Kruskal-Wallis
      test. RESULTS: There was a statistically significant correlation between
      dexamethasone or morphine treatment and decreased levels and incidence of
      endodontic pain at 4, 8 and 24 h, but not at 48 h (P < 0.05). It was also
      observed that dexamethasone was significantly more effective (56.7% no pain) than
      morphine (43.3% no pain). CONCLUSION: Periapical infiltration of dexamethasone
      and morphine led to a considerable decrease in postoperative endodontic pain
      during the first 24 h after operation. Dexamethasone was more effective than
      morphine in pain reduction.

PMID- 22420476
TI  - Current status, crisis and trends in Chinese dental technicians.
AB  - BACKGROUND: Chinese dental technicians play a significant role in the globalised
      market of dental prosthesis fabrication, but this subject has not been
      investigated in detail. The demand for dental prostheses increases as individuals
      pay increasing attention to their oral health. Therefore, it is important to
      investigate the status of Chinese dental technicians. OBJECTIVE: To evaluate the
      current status of Chinese dental technicians. METHODS: Dental technicians'
      resumes, which reveal information regarding dental technician manpower, degrees,
      working age and salary, etc., were analysed and compared with those abroad. We
      also estimated the future demands of dental technician manpower, and discussed
      some potential solutions. RESULTS: There are fewer dental technicians in China
      than in other developed countries; they are also of a lower standard. Male
      technicians outnumber females. The education level of technicians is
      insufficient, and the education programme is still in its exploratory stage.
      CONCLUSIONS: The development of dental technician teams in China represents both
      an opportunity and a challenge. It is important to move forward from the current
      situation to yield long-term development. This article provides information on
      the Chinese dental technology industry, identifies the problems and offers
      solutions for its development.

PMID- 22420477
TI  - Trend in dental research output in Iran over a period of 20 years (1990-2009).
AB  - INTRODUCTION: The number of scientific papers is a conventional metric for the
      measurement of a country's research performance in a particular area. OBJECTIVE:
      To evaluate the trend in Iranian publications of dental research results in peer
      reviewed international scientific journals over the period 1999-2009, using
      national and international databases, and to compare the results with other
      countries. METHODS: The search process was performed by two independent persons
      in PubMed and Iranian Medline (IranMedex). Data extraction included the year of
      publication, total number of dental papers in each year, total number of Iranian
      dental papers in each year and number of papers with a high level of evidence;
      these were compared with those in other Asian countries. RESULTS: The total
      number of dental articles indexed in PubMed during the studied period was
      207,689, with 671 being written by researchers who stated their affiliation as
      Iran. Although the proportion of Iranian dental articles to all published dental
      articles was 0.01% in 1990, this increased to 1.4% in 2009. Of all clinical
      trials indexed in PubMed from 1990 to 2009, only 0.62% had an author from Iran.
      The collaboration rate of authors ranged between 1 and 10. Turkey and Iran had a
      larger number of dental research publications compared with other Asian countries
      assessed in this study. CONCLUSION: During the last two decades, there has been a
      considerable increase in the number of dental papers by Iranian researchers
      indexed in the PubMed database.

PMID- 22420478
TI  - Is the utilisation of dental care based on need or socioeconomic status? A study
      of dental care in Indonesia from 1999 to 2009.
AB  - OBJECTIVE: One of the goals of Indonesian health policy is 'Health for All'; this
      includes dental health care. Therefore, it is important to continually evaluate
      and dynamically assess the effects of government policies, particularly whether
      these policies promote or obstruct social justice. This study is intended to
      describe the need for and utilisation of dental care and how disparities in
      dental care provision to people of varying socioeconomic status (SES) have
      changed over time. METHODS: We used secondary cross-sectional data from the
      Indonesian Socioeconomic Surveys for 1999, 2001, 2003, 2005, 2007 and 2009. The
      concentration index was used to describe disparities in need for and utilisation
      of dental care. RESULTS: The concentration index showed a significant
      concentration of dental care utilisation among groups of higher SES. CONCLUSIONS:
      The use of dental care services is more dependent on ability to pay than on need
      for care. In addition, inequality in dental care in Indonesia persisted from 1999
      to 2009.

PMID- 22420479
TI  - High-acuity GIS mapping of private practice dental services in New Zealand: does
      service match need?
AB  - OBJECTIVES: New Zealand is a country with a relatively small population (4
      million people) distributed unevenly over a relatively large land area. Adult
      oral health services in New Zealand are almost all delivered through a market
      driven, private practice model and are funded directly by patient payments.
      Little attention has been given to the distribution of these services. This study
      reports the findings of a high-acuity examination of the distribution of private
      dental practices in New Zealand, using modern geographic information system (GIS)
      tools. METHODS: A total of 1,045 private dental practices in New Zealand were
      geocoded. These dental practices overlaid 1,909 area units. RESULTS: The highest
      practice: adult population ratios found in this study reflected the areas with
      the highest population densities of Maori and Pacific Islander people.
      CONCLUSIONS: Oral health has a substantial impact on health-related quality of
      life and the utilisation of dental care services can contribute to its
      improvement. As such, it is expected that access to care should be focused on the
      population groups with the highest degree of need. However, in a market-driven,
      mostly private practice model, such as that in New Zealand, available care is
      concentrated largely in areas of high socioeconomic status and in populations
      with lower levels of oral disease.

PMID- 22420481
TI  - Does smoking increase the incidence of postoperative complications in simple
      exodontia?
AB  - OBJECTIVE: To investigate whether smoking has adverse effects in simple
      exodontia. METHODS: A single-centre, prospective study of postoperative
      inflammatory complications in simple exodontia was performed. All procedures were
      conducted under similar and sterile conditions. Postoperative complications (PCs)
      in exodontia were classified as alveolar osteitis (AO) or alveolar infection (AI)
      and their incidences then added. RESULTS: A logistic regression model for PCs
      revealed tooth sectioning [odds ratio (OR) = 4.3, 95% confidence interval (CI)
      1.0-18.8; P = 0.050], smoking (OR = 4.5, 95% CI 1.0-18.9; P = 0.03) and amount of
      smoking (> 20 cigarettes/day: OR = 12.3, 95% CI 1.0-149.8; P = 0.04) to be
      associated with the occurrence of PCs. CONCLUSIONS: Tooth sectioning, smoking and
      degree of smoking are all associated with the development of PCs such as AO and
      AI after simple exodontia. Dentists must be alert to these factors when
      performing simple exodontia in smokers in view of the increased risk for PCs.

PMID- 22420480
TI  - Monitoring time-related trends in dental caries in permanent teeth in Japanese
      national surveys.
AB  - OBJECTIVES: According to dental examinations of 3- and 12-year-old children
      conducted throughout Japan, the prevalence of dental caries in children is
      decreasing. However, little is known about changes in the prevalence of dental
      caries in adults. This study analysed past and present prevalences of dental
      caries in permanent teeth and predicted future trends in dental caries in adults.
      METHODS: Data were sourced from nine national dental surveys conducted in Japan
      at 6-year intervals from 1957 to 2005. Data from oral examinations were recorded
      as indices of decayed, missing and filled teeth. RESULTS: The mean number of
      filled teeth increased markedly, whereas mean numbers of decayed teeth and
      missing teeth decreased substantially in people aged >= 40 years. By contrast,
      the mean number of filled teeth first increased and then decreased in groups aged
      5-39 years. CONCLUSIONS: Among Japanese respondents sampled in a series of cross
      sectional studies between 1957 and 2005, the incidence of dental caries in young
      adults decreased, suggesting a decrease in prevalences of dental caries in future
      generations. However, this tendency was not observed in respondents aged >= 40
      years. The results suggest adults will experience less dental caries in the near
      future.

PMID- 22420482
TI  - Human umbilical cord blood-derived very-small-embryonic-like stem cells with
      maximum regenerative potential?

PMID- 22420483
TI  - Hydrogen-bonding networks from first-principles: exploring the guanidine crystal.
AB  - Hydrogen bonding is among the most important interactions in molecular crystals,
      and examples are abundant. As a consequence of such interactions, many molecules
      crystallize in complex but intriguing structures, in contrast to the relatively
      simple packing principles of metallic or ionic solids. In this work, we present a
      computational approach based on plane-wave density-functional theory (DFT) and
      supercell techniques, aiming to understand and quantify hydrogen-bonded networks
      in the solid state and in two-, one-, and zero-dimensional fragments derived from
      the molecular crystal. With such methodology at hand, we investigate guanidine, a
      fitting example of a molecular crystal and an important compound for inorganic
      and organic chemistry alike. On the basis of our computations, we discuss the
      initially proposed layered structure of guanidine and identify both stabilizing
      and destabilizing cooperative interactions in the three crystalline dimensions.

PMID- 22420484
TI  - Talcum induced pneumoconiosis following inhalation of adulterated marijuana, a
      case report.
AB  - BACKGROUND: Talcosis, a granulomatous inflammation of the lungs caused by
      inhalation of talcum dust, is a rare form of pneumoconiosis. Besides inhalative
      occupational exposure, intravenous abuse of adulterated drugs is a major cause
      for this condition. Minerals such as talcum (magnesium silicate) and sand
      (predominant silicon dioxide) are used to increase both volume and weight of
      illicit substances. In intravenous heroin-abuse, talcosis is a well-known
      complication. Here we describe a case of talcosis caused by inhalative abuse of
      adulterated marijuana. CLINICAL HISTORY: A 29-year old man presented with
      persistent fever, dyspnea and cervical emphysema. He admitted consumption of
      'cut' marijuana for several years, preferentially by water pipe smoking.
      MORPHOLOGIC FINDINGS: Lung-biopsies showed chronic interstitial lung disease,
      anthracotic pigments and birefringent material. Energy dispersive x-ray
      spectroscopy revealed silicon-containing particles (1-2 MUm) and fine aluminum
      particles (< 1 MUm), magnesium and several other elements forming a spectrum
      compatible with the stated water pipe smoking of talcum-adulterated marijuana.
      CONCLUSIONS: The exacerbated chronic interstitial lung disease in a 29-year old
      patient could be attributed to his prolonged abuse of talcum-adulterated marjuana
      by histopathology and x-ray spectroscopy. Since cannabis consumption is widely
      spread among young adults, it seems to be justified to raise attention to this
      form of interstitial pulmonary disease. VIRTUAL SLIDES: The virtual slide(s) for
      this article can be found here: http://www.diagnomx.eu/vs/krause/html/start.html.

PMID- 22420485
TI  - Relationship between conventional sperm parameters and motile sperm organelle
      morphology examination (MSOME).
AB  - With the motile sperm organelle morphology examination (MSOME), spermatozoa
      morphology may be assessed directly on motile spermatozoa at high magnification
      (up to 6600*). This procedure describes more precisely spermatozoa abnormalities,
      especially head vacuoles. However, no consensus has been established concerning
      normal or abnormal MSOME criteria. The aim of our study was to define MSOME
      vacuole criteria assessed objectively with a digital imaging system software to
      establish a potential relationship between conventional semen parameters. A total
      of 440 semen samples were obtained from males consulting in Rouen University
      Hospital Reproductive Biology Laboratory. Conventional semen analysis (volume,
      sperm concentration, progressive motility, vitality and morphology) and MSOME
      assessment {sperm head length, width and area as well as vacuole number, vacuole
      area and relative vacuole area to sperm head [RVA (%) = [vacuole area
      (MUm(2))/head area (MUm(2))] * 100)]} were performed for each semen sample. Among
      our 440 males, 109 presented normal conventional semen parameters and 331
      abnormal ones. Sperm head vacuoles were significantly larger in abnormal semen
      samples (p < 0.0001). RVA was the most discriminative MSOME criterion between
      normal and abnormal semen samples according to ROC curves analysis, and was
      negatively correlated with poor sperm morphology (r = -0.53, p < 0.0001). We
      concluded to (i) the normal occurrence of vacuoles in sperm head whatever the
      normality or abnormality of semen parameters, (ii) the discriminative function of
      the RVA to distinguish semen samples with normal and abnormal parameters, and
      (iii) the strong correlation between high RVA and poor sperm morphology.

PMID- 22420487
TI  - Telogen effluvium after oral albendazole.

PMID- 22420486
TI  - Prostate cancer in elderly Croatian men: 5-HT genetic polymorphisms and the
      influence of androgen deprivation therapy on osteopenia--a pilot study.
AB  - BACKGROUND: The aim of this study was to determine the relationship between body
      mass index, biochemical parameters, and 5-hydroxytryptamine (5-HT) genetic
      polymorphisms and prostate dysfunction in an elderly general male population.
      RESULTS: One hundred and seventeen elderly male subjects [60 men without symptoms
      of prostate hyperplasia, 42 men with untreated benign prostatic hyperplasia
      (BPH), and 15 men with prostate cancer (PCa)] treated with finasteride or
      flutamide were included. Multiple comparisons showed significant difference in
      age, T-score, concentration of phosphorus, calcium, C-reactive protein, and
      prostate-specific antigen (PSA) between the groups. T-score was the lowest and
      phosphorus concentration was the highest in the PCa group. Highest PSA, proteins,
      calcium, and Hekal's formula score were found in the BPH group. Patients with PCa
      were more frequent GG+GA carriers of 5-HT1B 1997A/G gene polymorphism (p=0.035).
      Univariate regression analysis showed association of PCa-treated subjects with
      age (p=0.010) and 5-HT1B genetic polymorphism (p=0.018). Antiandrogen therapy
      affects T-score (p=0.017), serum phosphorus (p=0.008), glucose (p=0.036), and
      total proteins (p=0.050). Multivariate-stepwise logistic regression analysis
      showed the significant association of treated PCa with age (p=0.028) and
      inorganic phosphorus (p=0.005), and a marginal association with ultrasonographic
      T-score (p=0.052). CONCLUSIONS: Antiandrogen therapy might induce bone mineral
      loss in elderly PCa patients. Preliminary data imply that the genetic variants of
      the 5-HT1B receptor might be associated with PCa.

PMID- 22420488
TI  - How to infer reliable diploid genotypes from NGS or traditional sequence data:
      from basic probability to experimental optimization.
AB  - The use of diploid sequence markers is still challenging despite the good quality
      of the information they provide. There is a common problem to all sequencing
      approaches [traditional cloning and sequencing of PCR amplicons as well as next
      generation sequencing (NGS)]: when no variation is found within the sequences
      from a given individual, homozygozity can never be asserted with certainty. As a
      consequence, sequence data from diploid markers are mostly analysed at the
      population (not the individual level) particularly in animal studies. This study
      aims at contributing to solve this. Using the Bayes theorem and the binomial law,
      useful results are derived, among which: (i) the number of sequence reads per
      individual (or sequencing depth) which is required to ensure, at a given
      probability threshold, that some heterozygotes are not considered erroneously as
      homozygotes, as a function of the observed heterozygozity (H(o) ) of the locus in
      the population; (ii) a way of estimating H(o)  from low coverage NGS data; (iii)
      a way of testing the null hypothesis that a genetic marker corresponds to a
      single and diploid locus, in the absence of data from controlled crosses; (iv)
      strategies for characterizing sequence genotypes in populations minimizing the
      average number of sequence reads per individual; (v) a rationale to decide which
      are the variations that one needs to consider along the sequence, as a function
      of the sequencing depth affordable, the level of polymorphism desired and the
      risk of sequencing error. For traditional sequencing technology, optimal
      strategies appear surprisingly different from the usual empirical ones. The
      average number of sequence reads required to obtain 99% of fully determined
      genotypes never exceeds six, this value corresponding to the worst situation when
      H(o)  equals 0.6. This threshold value of H(o)  is strikingly stable when the
      tolerated proportion of nonfully resolved genotypes varies in a reasonable range.
      These results do not rely on the Hardy-Weinberg equilibrium assumption or on
      diallelism of nucleotidic sites.

PMID- 22420489
TI  - Relative risk of death from exposure to air pollutants: a short-term (2003-2007)
      study in Mexicali, Baja California, Mexico.
AB  - Studies have shown associations between respiratory diseases and air pollutants
      in Mexicali, Mexico; however, none have addressed relative risk (RR) of death. By
      using Poisson regression models, we quantified the RR by exposure for:
      particulate matter (PM(10), PM(2.5)), carbon monoxide (CO), nitrogen dioxide
      (NO(2)), ozone (O(3)), and sulfur dioxide (SO(2)) over a 5-year period and by
      climate (winter or summer). RRs were estimated utilizing each pollutant (single
      pollutant model) on the same day as pollutant concentration were measured (lag 0)
      and up to 7 days later to the pollutant measurements (lag 7). Significant
      associations were found in RRs for one interquartile range increment of the
      corresponding pollutant, such as: PM(2.5) lagged 5 days in winter and for the 5
      year period (RR, 1.041 and 1.028, respectively); CO lagged 1 day in winter and
      for the 5-year period (RR, 1.044 and 1.032, respectively); NO(2) on the current
      day (lag 0) in summer (RR = 1.037); and SO(2) lagged one day for the 5-year
      period (RR = 1.023).

PMID- 22420491
TI  - Three centuries of Eastern European and Altai lead emissions recorded in a
      Belukha ice core.
AB  - Human activities have significantly altered atmospheric Pb concentrations and
      thus, its geochemical cycle, for thousands of years. Whereas historical Pb
      emissions from Western Europe, North America, and Asia are well documented, there
      is no equivalent data for Eastern Europe. Here, we present ice-core Pb
      concentrations for the period 1680-1995 from Belukha glacier in the Siberian
      Altai, assumed to be representative of emissions in Eastern Europe and the Altai.
      Pb concentrations and (207)Pb/(206)Pb ratios were strongly enhanced during the
      period 1935-1995 due to the use of Pb additives in Russian gasoline mined in the
      Rudny Altai. Comparable to Western Europe and North America, Eastern European Pb
      emissions peaked in the 1970s. However, the subsequent downward trend in Eastern
      Europe was mainly caused by the economic crisis in the U.S.S.R. and not by a
      phase-out of leaded gasoline. Pb concentrations in the period 1680-1935,
      preceding the era of intensified industrialization in Russia, reflect the history
      of local emissions from Rudny Altai mining and related metallurgical processing
      primarily for the production of Russian coins. During this time, Altai ore Pb
      contributed about 40% of the regional atmospheric Pb.

PMID- 22420490
TI  - B cell repopulation after alemtuzumab induction-transient increase in
      transitional B cells and long-term dominance of naive B cells.
AB  - In organ transplantation, the composition of the B-cell compartment is
      increasingly identified as an important determinant for graft outcome. Whereas
      naive and transitional B cells have been associated with long-term allograft
      survival and operational tolerance, memory B cells have been linked to decreased
      allograft survival. Alemtuzumab induction therapy effectively depletes B cells,
      but is followed by rapid repopulation up to levels exceeding base line. The
      characteristics of the repopulating B cells are currently unknown. We studied the
      phenotypic and functional characteristics of B cells longitudinally in 19 kidney
      transplant recipients, before and at 6, 9 and 12 months after alemtuzumab
      induction therapy. A transient increase in transitional B cells and cells with
      phenotypic characteristics of regulatory B cells, as well as a long-term
      dominance in naive B cells was found in alemtuzumab-treated kidney transplant
      recipients, which was not influenced by conversion from tacrolimus to sirolimus.
      At all time-points after treatment, B cells showed unaltered proliferative and
      IgM-producing capacity as compared to pretransplant samples, whereas the ability
      to produce IgG was inhibited long-term. In conclusion, induction therapy with
      alemtuzumab results in a long-term shift toward naive B cells with altered
      phenotypic and functional characteristics.

PMID- 22420492
TI  - Effects of dehydroepiandrosterone sulphate (DHEAS) replacement on insulin action
      and quality of life in hypopituitary females: a double-blind, placebo-controlled
      study.
AB  - OBJECTIVE: Addition of dehydroepiandrosterone sulphate (DHEAS) to standard
      pituitary replacement may improve quality of life and glucose metabolism.
      Conflicting results from the previous work probably relate to differences in
      populations studied and assessment techniques used. We examined the effects of
      DHEAS on insulin action and the quality of life in female patients with
      hypopituitary hypoadrenalism. DESIGN: Randomized, double-blind, placebo
      controlled, crossover design was used. Patients received either DHEAS 50 mg daily
      or placebo for 12 weeks. PATIENTS: Fourteen hypopituitary females on stable
      standard replacement therapy and with low DHEAS were enrolled. MEASUREMENTS:
      Insulin action by euglycaemic hyperinsulinaemic clamp and extensive quality of
      life parameters were assessed after each treatment. RESULTS: Serum DHEAS (DHEAS
      5.4 +/- 0.8 vs placebo <0.8 +/- 0.0 MUm; P < 0.001) and androstenedione (DHEAS
      4.1 +/- 0.8 vs placebo 1.3 +/- 0.2 nm; P < 0.05) rose to within the normal range
      after DHEAS 50 mg daily. There were no differences between treatments in
      testosterone, sex hormone-binding globulin (SHBG) or IGF-1. Quality of life
      measures were unchanged after DHEAS. There were no differences between treatments
      in fasting glucose, serum insulin, HbA1c or in insulin action (glucose infusion
      rates required to maintain euglycaemia; DHEAS 21.9 +/- 2.5 vs placebo 24.5 +/-
      2.1 MUmol/kg/min; P = 0.4). Triglyceride concentrations were lower following
      DHEAS (DHEAS 1.24 +/- 0.18 vs placebo 1.41 +/- 0.19 mm; P < 0.05) but other lipid
      parameters remained unchanged. CONCLUSION: There were no differences compared
      with placebo in quality of life or insulin action after DHEAS replacement therapy
      for 12 weeks. These results do not provide evidence for the addition of DHEAS to
      standard hypopituitary replacement therapy.

PMID- 22420493
TI  - The peer review show: remains essential but always room for improvement.

PMID- 22420494
TI  - Limited joint mobility syndrome in patients with diabetes.

PMID- 22420495
TI  - Global health, global responsibilities.

PMID- 22420496
TI  - Evidence-informed health policy - the crucial role of advocacy.

PMID- 22420497
TI  - New therapies for chronic hepatitis C infection: a systematic review of evidence
      from clinical trials.
AB  - INTRODUCTION: Hepatitis C virus (HCV) affects approximately 3% of the world
      population. The current standard of care for treatment of HCV is a combination of
      pegylated interferon and ribavirin. Approximately 10% of patients will stop
      treatment and 30% of patients require dose reduction because of side effects. For
      genotype 1 HCV-infected patients, only 40% of patients will achieve undetectable
      viral load 26 weeks posttreatment. AIMS: The objectives of this review were to
      identify new treatments that are in clinical trials. These include boceprevir and
      telaprevir which are in routine clinical use and form part of the American
      Association for the Study of Liver Diseases (AASLD) 2011 guidelines as well as
      drugs based on observational studies, improving/modifying ribavirin or interferon
      based therapies, modifying the host response and finally the use of direct-acting
      antiviral agents (DAA). MATERIALS AND METHODS:   MEDLINE and EMBASE databases
      were searched from 2008 to 2011 for treatments for hepatitis C. Furthermore,
      abstracts and poster presentations for the annual European Association Study of
      the Liver, AASLD, Digestive Disease Week and Asian Pacific Association for the
      study of the Liver were searched for relevant material. RESULTS: All four classes
      of DAA; NS3/NS4a serine protease inhibitors, cyclophilin inhibitors, NS5b
      polymerase inhibitors and NS5a inhibitors, show good success rates. Trials have
      been performed without ribavirin or interferon and demonstrate good antiviral
      activity with a decreased side effect profile. Combinations of DAA are a
      promising area of research with a high success rate. CONCLUSIONS: Clinical trials
      show that future HCV therapy could be personalised, achieve higher success rates
      with decreased adverse incidents.

PMID- 22420498
TI  - Triglyceride-rich lipoproteins in chronic kidney disease patients undergoing
      maintenance haemodialysis treatment.
AB  - OBJECTIVE: Plasma triglyceride (TG) levels were reported to be high in chronic
      kidney disease (CKD) patients undergoing haemodialysis (HD) treatment. One of the
      atherogenic causes of hypertriglyceridemia is the increase in TG-rich lipoprotein
      remnants, which are equivalent to remnant-like particle cholesterol (RLP-C).
      Here, we compared the plasma levels of TG, a representative indicator of TG-rich
      lipoproteins and RLP-C, as well as the TG/RLP-C ratio between CKD patients
      undergoing HD and controls, in an effort to elucidate the atherogenicity of TG
      rich lipoproteins in CKD patients on HD. MATERIALS AND METHODS: Plasma lipid and
      apo(lipo)protein levels and the TG/RLP-C ratio were compared between 49 CKD
      patients undergoing HD and 627 controls. Blood sampling for lipid and apoprotein
      analysis was performed in a 12-h fasting state. Controls were divided into four
      subgroups according to TG level (from highest to lowest). RLP-C and
      apo(lipo)proteins were measured using the immunoprecipitation method and
      turbidimetric immunoassay, respectively. In addition, a comparison between HD
      patients and age-, gender-, and plasma TG level-matched controls was performed.
      RESULTS: Plasma TG levels were 107 +/- 70 (mean +/- SD) mg/dl in HD patients and
      115 +/- 72 mg/dl in controls. Plasma RLP-C levels were 6.7 +/- 4.5 mg/dl in HD
      patients and 4.6 +/- 3.5 mg/dl in the controls (p < 0.0001). RLP-C levels
      decreased in descending order from the highest to the lowest TG group in
      controls. RLP-C levels were higher in HD patients than in controls with plasma TG
      levels of < 150 mg/dl (p < 0.0001). TG/RLP-C ratios were 19.0 +/- 12.0 in HD
      patients and 25.9 +/- 9.5 in controls (p < 0.0001). This ratio was significantly
      lower in HD patients than in all four TG subgroups. The comparison between HD
      patients and age-, gender-, plasma TG-matched controls revealed identical
      results. CONCLUSION: Plasma RLP-C levels were high, and the TG/RLP-C ratio was
      low in CKD patients undergoing HD treatment. These findings indicate that total
      plasma TG-rich lipoprotein levels were not increased, but the distribution of
      plasma TG-rich lipoproteins were skewed towards remnant fractions in CKD patients
      undergoing HD treatment; these plasma TG-rich lipoproteins appear to be more
      atherogenic than those in controls.

PMID- 22420500
TI  - Electronic cigarettes: new kit on the rack.

PMID- 22420501
TI  - Anthropometric discriminators of the risk of high blood pressure amongst public
      schoolchildren in Gujarat, India.

PMID- 22420502
TI  - Voltage-gated Ca2+ channels as key mediators of iron-transport and iron-overload
      cardiomyopathy: L-type vs. T-type Ca+ channels.

PMID- 22420503
TI  - Video-thoracoscopic enucleation of esophageal leiomyoma.
AB  - BACKGROUND: Leiomyoma is the most common benign tumor of the esophagus. Surgical
      enucleation is indicated in case of symptoms or an unclear diagnosis, and open
      thoracotomy has long been the standard approach for this procedure. However,
      enucleation through video assisted thoracoscopic surgery (VATS) has been
      developed as a preferred approach for most lesions in recent years. METHOD:
      Herein we report our twelve patients (seven men and five women, with median age
      of 42 years) from 2001 to 2009, who underwent enucleation through VATS for
      esophageal leiomyomas, with a size from 1 to 8 cm in diameter (median: 5), and at
      different locations, from the thoracic outlet to near the diaphragmatic level of
      the thoracic esophagus. Intraoperative fiberoptic esophagoscopy was performed in
      two patients for localization by illumination. A right-sided approach was
      performed in eight cases (upper two thirds of esophagus) and the left-sided in
      another four cases (lower third of esophagus). RESULT: The median operative time
      was 95 minutes (70 to 230 minutes). Four of them required small utility incisions
      (4-6 cm) for better exploration and manipulation. There were no major
      complications, such as death or empyema due to leaks from mucosal tears, and the
      presenting symptoms were improved during the follow-up period, from 12 to 98
      months. CONCLUSION: VATS can be considered as an initial approach for most
      patients with esophageal leiomyomas, even large in size, irregular in shape, or
      at unfavorable location. It is a safe, minimally invasive, and effective
      treatment. However, conversion to open thoracotomy should be required for the
      sake of clinical or technical concern.

PMID- 22420504
TI  - Cannabinoid receptor 2 activation reduces intestinal leukocyte recruitment and
      systemic inflammatory mediator release in acute experimental sepsis.
AB  - INTRODUCTION: Cannabinoid receptor 2 (CB2R) expression is upregulated during
      sepsis. However, there are conflicting results regarding the effects of CB2R
      modulation in the hyperinflammatory phase of the disease. The aim of this study
      was therefore to investigate the effects of CB2R manipulation on leukocyte
      activation within the intestinal microcirculation in two acute experimental
      sepsis models. METHODS: In the endotoxemia model we studied four groups of Lewis
      rats: controls, lipopolysaccharide (LPS), LPS + CB2R agonist HU308 (2.5 mg/kg),
      and LPS + CB2R antagonist AM630 (2.5 mg/kg). In the colon ascendens stent
      peritonitis (CASP)-induced sepsis model we also studied four groups: sham group,
      CASP and CASP + CB2R agonist (HU308, 2.5 or 10 mg/kg). Intravital microscopy was
      performed 2 hours following LPS/placebo administration or 16 hours following
      CASP/sham surgery to quantify intestinal leukocyte recruitment. Additionally,
      hemodynamic monitoring, histological examinations and measurements of
      inflammatory mediators were performed. RESULTS: HU308 administration
      significantly reduced intestinal leukocyte adhesion in both acute sepsis models.
      The systemic levels of inflammatory mediators were significantly reduced by 10
      mg/kg HU308 treatment in CASP animals. CONCLUSION: CB2R activation reduces
      leukocyte activation and systemic release of inflammatory mediators in acute
      experimental sepsis. Drugs targeting the CB2R pathway may have therapeutic
      potential in sepsis.

PMID- 22420505
TI  - Development of a multianalyte enzyme-linked immunosorbent assay for permethrin
      and aroclors and its implementation for analysis of soil/sediment and house dust
      extracts.
AB  - Development of a multianalyte enzyme-linked immunosorbent assay (ELISA) for
      detection of permethrin and aroclors 1248 or 1254 and implementation of the assay
      for analysis of soil/sediment samples are described. The feasibility of using the
      multianalyte ELISA to monitor aroclors 1254 and permethrin simultaneously was
      tested with permethrin and aroclor standards and with aroclor- and permethrin
      containing soil/sediment and house dust samples. Comparison of the I50 and I20
      values of the multianalyte with those of a single-analyte assay revealed similar
      results, and multianalyte ELISA determination of analyte amounts in soil/sediment
      dust samples yielded similar results to those of a single-analyte assay. A single
      analyte assay of permethrin content in permethrin-containing dust samples showed
      that the ELISA can determine the analyte accurately in samples with dust matrix
      contents ranging from 6.25 to 100 mg as indicated by the good correlation between
      the results of the immunoassay and those of the gas chromatography analysis.

PMID- 22420506
TI  - Does a third party observer affect neuropsychological test performance? It
      depends.
AB  - This study is a meta-analysis of available literature examining the effect of an
      observer on cognitive task performance. Of the 210 identified relevant articles,
      62 met inclusion criteria yielding a final sample with 4405 individuals (2496
      observed cases, 1909 not observed). The overall effect size was significant (d=
      0.24), i.e., the presence of an observer was associated with poorer performance.
      However results were moderated by the effect size calculation method, cognitive
      domain, visibility of the observer, and number of observers. Attention,
      learning/memory, and delayed recall tasks were most adversely impacted by the
      presence of an observer.

PMID- 22420507
TI  - Europium(III) DOTA-tetraamide complexes as redox-active MRI sensors.
AB  - PARACEST redox sensors containing the NAD(+)/NADH mimic N-methylquinolinium
      moiety as a redox-active functional group have been designed and synthesized. The
      Eu(3+) complex with two quinolinium moieties was nearly completely CEST-silent in
      the oxidized form but was "turned on" upon reduction with beta-NADH. The CEST
      effect of the Eu(3+) complex containing only one quinolinium group was much less
      redox-responsive but showed an unexpected sensitivity to pH in the
      physiologically relevant pH range.

PMID- 22420508
TI  - Gene expression signatures defining fundamental biological processes in
      pluripotent, early, and late differentiated embryonic stem cells.
AB  - Investigating the molecular mechanisms controlling the in vivo developmental
      program postembryogenesis is challenging and time consuming. However, the
      developmental program can be partly recapitulated in vitro by the use of cultured
      embryonic stem cells (ESCs). Similar to the totipotent cells of the inner cell
      mass, gene expression and morphological changes in cultured ESCs occur
      hierarchically during their differentiation, with epiblast cells developing
      first, followed by germ layers and finally somatic cells. Combination of high
      throughput -omics technologies with murine ESCs offers an alternative approach
      for studying developmental processes toward organ-specific cell phenotypes. We
      have made an attempt to understand differentiation networks controlling
      embryogenesis in vivo using a time kinetic, by identifying molecules defining
      fundamental biological processes in the pluripotent state as well as in early and
      the late differentiation stages of ESCs. Our microarray data of the
      differentiation of the ESCs clearly demonstrate that the most critical early
      differentiation processes occur at days 2 and 3 of differentiation. Besides
      monitoring well-annotated markers pertinent to both self-renewal and potency
      (capacity to differentiate to different cell lineage), we have identified
      candidate molecules for relevant signaling pathways. These molecules can be
      further investigated in gain and loss-of-function studies to elucidate their role
      for pluripotency and differentiation. As an example, siRNA knockdown of MageB16,
      a gene highly expressed in the pluripotent state, has proven its influence in
      inducing differentiation when its function is repressed.

PMID- 22420510
TI  - Mohs micrographic surgery: examination audit of processing techniques.

PMID- 22420509
TI  - Factors associated with delayed diagnosis of tuberculosis in hospitalized
      patients in a high TB and HIV burden setting: a cross-sectional study.
AB  - BACKGROUND: The most essential components of TB control are early diagnosis and
      adequate treatment. Delay in the diagnosis and treatment of tuberculosis may
      result in more extensive disease and more complications, increase severity of the
      disease and is associated with higher risk of mortality. The purpose of this
      study was to identify factors associated with delayed diagnosis of TB in
      hospitalized patients. METHODS: We conducted a cross-sectional study in a
      general, tertiary care, university-affiliated hospital. Adult patients with TB
      that were hospitalized were identified retrospectively, and risk factors for
      delayed diagnosis were collected. RESULTS: The median delay until diagnosis was 6
      days (IQR: 2-12 days). One hundred and sixty six (54.4%) patients were diagnosed
      <= 6 days, and 139 (45.6%) > 6 days after admission. The main factors associated
      with diagnostic delay (> 6 days) were extra-pulmonary TB and negative sputum
      smear. CONCLUSIONS: Although hospitalization permits a rapid management of the
      patient and favors a faster diagnosis, we found an unacceptable time delay before
      the diagnosis of pulmonary TB was made. Future studies should focus on attempt to
      explain the reasons of diagnostic retard in the patients with the characteristics
      related to delay in this study.

PMID- 22420511
TI  - Morphology and development of the placentae in Eulamprus quoyii group skinks
      (Squamata: Scincidae).
AB  - Frequent evolutionary changes in reproductive mode have produced a wide range of
      placental structures in viviparous squamate reptiles. Closely related species
      with different placental structures and resolved phylogenetic relationships are
      particularly useful for reconstructing how placentae might have transformed
      during the evolutionary process. We used light microscopy to study placental
      morphology in mid- to late stage embryos of four closely related species of
      Eulamprus, a genus of viviparous scincid lizards that we had reason to suspect
      may display significant interspecific variation in placental morphology. Embryos
      from all four species possess a chorioallantoic placenta, an omphaloplacenta and
      an interomphalopleuric membrane, characteristics present in other viviparous
      skinks. However, unlike other viviparous skinks but characteristic of oviparous
      skinks, the allantois expands to surround the yolk sac in each species,
      supplanting the omphalopleure with a larger area of chorioallantois until a
      chorioallantoic placenta surrounds the entire egg in one specimen that is only a
      few days from birth. All four Eulamprus species share the same extraembryonic
      membrane morphology, but the cellular morphology of the uterine epithelium in the
      chorioallantoic placenta and omphaloplacenta varies between species. We
      determined that the interomphalopleuric membrane is a shared derived character of
      the Eulamprus quoyii species group. New phylogenetic information indicates that
      variation in the chorioallantoic placenta is a result of two independent
      transitions, but that variation in the omphaloplacenta can be explained using a
      single change within the species studied. Our results indicate that E. quoyii
      group skinks are a valuable model for investigating the evolution of viviparity,
      as extraembryonic membrane development in these species shows features
      characteristic of both oviparous and viviparous skinks.

PMID- 22420512
TI  - Spectral induced polarization signatures of hydroxide adsorption and mineral
      precipitation in porous media.
AB  - The spectral induced polarization (SIP) technique is a promising approach for
      delineating subsurface physical and chemical property changes in a minimally
      invasive manner. To facilitate the understanding of position and chemical
      properties of reaction fronts that involve mineral precipitation in porous media,
      we investigated spatiotemporal variations in complex conductivity during
      evolution of urea hydrolysis and calcite precipitation reaction fronts within a
      silica gel column. The real and imaginary parts of complex conductivity were
      shown to be sensitive to changes in both solution chemistry and calcium carbonate
      precipitation. Distinct changes in imaginary conductivity coincided with
      increased hydroxide ion concentration during urea hydrolysis. In a separate
      experiment focused on the effect of hydroxide concentration on interfacial
      polarization of silica gel and well-sorted sand, we found a significant
      dependence of the polarization response on pH changes of the solution. We propose
      a conceptual model describing hydroxide ion adsorption behavior in silica gel and
      its control on interfacial polarizability. Our results demonstrate the utility of
      SIP for noninvasive monitoring of reaction fronts, and indicate its potential for
      quantifying geochemical processes that control the polarization responses of
      porous media at larger spatial scales in the natural environment.

PMID- 22420513
TI  - Prion disease: chemotherapeutic strategies.
AB  - Prion diseases, also known as transmissible spongiform encephalopathies, are
      invariably fatal neurodegenerative diseases for which there are no efficacious
      treatments. Thousands of compounds have been screened for anti-prion effect, and
      yet of those that have effect in vitro, very few show effect in vivo, especially
      if administered in the later stages of disease. However, with new techniques for
      early diagnosis being developed, and with further insight into the pathogenesis
      of early disease, including the role of oligomers and the contribution of
      accessory molecules and signalling cascades, the chance of finding a therapeutic
      strategy is increasing. Beyond clinical therapy, there is increasing need to find
      effective decontaminants for blood supplies, as variant Creutzfeldt Jakob Disease
      (vCJD) is transmissible by blood. Non-toxic preventative therapies are also
      needed, with ongoing cases of Bovine Spongiform Encephalopathy (BSE) and the
      spread of Chronic Wasting Disease (CWD) being a growing concern. A primary target
      for therapy has been the conversion of the normal form of prion protein (PrPC) to
      its abnormal counterpart (PrPSc). Many of the chemotherapeutic agents with
      antiprion effect share structural similarities, often being polyanionic or
      polycyclic. They may directly bind PrPC or PrPSc, or they may redistribute,
      sequester, or down-regulate PrPC, thus preventing its conversion. There have also
      been some novel approaches, including trapping PrPSc in a multimeric form such
      that it can no longer cause conversion, increasing clearance of PrPSc, targeting
      accessory molecules which play a role in conversion, targeting pathways which
      lead to neurodegeneration, and stem cell therapy. It may be that a combination of
      compounds will be necessary for maximal effect and there is evidence that
      synergistic responses occur with dual therapy. This updated review focuses
      primarily on chemicalbased treatments in light of developments in diagnostic
      technologies, including results from recent clinical trials, and proposes some
      promising new targets for prion therapy.

PMID- 22420514
TI  - Mitochondrial dysfunction and antioxidant therapy in sepsis.
AB  - Sepsis and septic shock are the major causes of death in intensive care units.
      Oxidative damage to mitochondria is involved in the development of organ
      dysfunction associated with sepsis. This syndrome is caused by an excessive
      defensive and inflammatory response characterised by a massive increases of
      reactive oxygen species (ROS), nitric oxide (NO) and inflammatory cytokines.
      Under normal circumstances, complex interacting antioxidant defense systems
      control oxidative stress within mitochondria The consequences of sepsis is a
      systemic damage to the vascular endothelium, impaired tissue and a compromised
      whole body respiration, antioxidant depletion and mitochondrial respiratory
      dysfunction with diminished levels of ATP and O2 consumption. In general, ROS are
      essential to the functions of cells and particularly immune cells, but adequate
      levels of antioxidant defenses are required to protect against the harmful
      effects of excessive ROS production. This review considers the process of sepsis
      from a mitochondrial perspective, discussing strategies for the targeted delivery
      of antioxidants to mitochondria. We will provide a summary of the following
      areas: the cellular metabolism of ROS and its role in pathophysiological
      processes such as sepsis; currently available antioxidants and possible reasons
      for their efficacy and inefficacy in ameliorating oxidative stress-mediated
      diseases; and recent developments in mitochondria-targeted antioxidants and the
      future implications for such approaches in patients.

PMID- 22420515
TI  - Necrotizing acute pancreatitis current status - emerging new strategies in
      surgical management.
AB  - Despite that pancreatic necrosis complicates only 15 % of cases of acute
      pancreatitis (AP), it is associated with high morbidity and considerable
      mortality. In an attempt to improve prognosis, many surgical strategies have been
      described during the last few decades. Currently, necrosectomy remains the
      cornerstone in the surgical treatment of infected pancreatic necrosis and in
      selected cases of sterile necrotizing pancreatitis. Following necrosectomy,
      continuous closed lavage is recommended by many authors, while closed abdominal
      packing /drainage and repeated planned necrosectomies- commonly using the zipper
      technique-are also acceptable alternative strategies. Open abdomen (laparostomy)
      is rarely indicated in carefully selected cases (typically in abdominal
      compartment syndrome associated with necrotizing AP). During the last decade,
      minimally invasive techniques (including percutaneous drainage, retroperitoneal
      endoscopic approach, transgastric endoscopic approach etc) have been extensively
      studied by some groups not only in the management of pancreatic abscesses and /
      or pseudocysts, but also as primary methods of treatment of necrotizing AP.
      Results have been impressive, but experience currently is limited to only a few
      centers around the world.

PMID- 22420516
TI  - Pharmacological management of chronic constipation in older adults.
AB  - Chronic constipation in older adults has multiple etiologies, and many of these
      factors are interrelated. An initial medical history and physical examination can
      provide relevant clues to the causes of the problem. The Rome III classification
      system of functional constipation is useful in clinical practice to help
      clinicians identify symptoms and confirm a diagnosis. Additionally, the Bristol
      Stool Scale is a valuable medical aid designed to assist patients in describing
      bowel patterns in a way that is more useful for diagnosis and evaluation of
      treatment methods. Pharmacological management, along with dietary changes and
      patient education, is the initial approach to treat patients with idiopathic
      chronic constipation. Consensus statements support a five-step care approach for
      patients with constipation. Knowledge of this approach will help clinicians in
      prescribing the appropriate medications along with patient education.

PMID- 22420518
TI  - Ageism among health care providers and interventions to improve their attitudes
      toward older adults: an integrative review.
AB  - The purpose of this study was to review relevant literature on ageism among
      health care providers and assess interventions used to improve their attitudes
      toward older adults. Literature published between 1983 and 2011 was reviewed
      using the keywords attitudes, older adults, nursing, and nursing students using
      CINAHL, MEDLINE, and the Education Resources Information Center. Previous
      relevant research is discussed and includes studies categorized according to
      health care provider populations: (a) nurses, (b) nursing students, (c) medical
      students, and (d) direct care workers. Studies in nursing and medical professions
      that highlight ageism have been conducted; however, there is a gap in the
      literature concerning ageism among direct care workers. This often neglected, yet
      critical population of health care providers is essential to the care of older
      adults; recommendations regarding their training and mentoring are emphasized.

PMID- 22420519
TI  - Automated technology to speed recognition of signs of illness in older adults.
AB  - Our team has developed a technological innovation that detects changes in health
      status that indicate impending acute illness or exacerbation of chronic illness
      before usual assessment methods or self-reports of illness. We successfully used
      this information in a 1-year prospective study to alert health care providers so
      they could readily assess the situation and initiate early treatment to improve
      functional independence. Intervention participants showed significant
      improvements (as compared with the control group) for the Short Physical
      Performance Battery gait speed score at Quarter 3 (p = 0.03), hand grip-left at
      Quarter 2 (p = 0.02), hand grip-right at Quarter 4 (p = 0.05), and the GAITRite
      functional ambulation profile score at Quarter 2 (p = 0.05). Technological
      methods such as these could be widely adopted in older adult housing, long-term
      care settings, and in private homes where older adults wish to remain independent
      for as long as possible.

PMID- 22420520
TI  - Potential food-drug interactions in long-term care.
AB  - Medication administration at mealtimes may result in food-drug interactions.
      Older adults are especially at risk of food-drug interactions leading to adverse
      drug effects and subtherapeutic responses. Research on potential food-drug
      interactions is limited and dated. This study examined the frequency of potential
      food-drug interactions in long-term care. Forty-nine percent of drugs
      administered at mealtimes had potential for interaction, with cardiovascular
      medications given most frequently. The frequency of potential interactions makes
      this phenomenon critically important to review. Collaboration between nurses and
      pharmacists may identify optimal medication scheduling. Nurses can enhance care
      by identifying strategies to limit interactions through knowledge and creative,
      collaborative administration schedules.

PMID- 22420521
TI  - Use of day centers for respite by help-seeking caregivers of individuals with
      dementia.
AB  - Addressing the use of respite services by caregivers of individuals with dementia
      is important to improving social support among this vulnerable group. This
      article uses theory to conceptualize the behavioral, normative, and control
      beliefs that caregivers of individuals with dementia associate with the use of
      out-of-home day centers for respite. Interviews and focus groups with 36
      caregivers were conducted to explore the beliefs of both users and nonusers of
      these services. While service users held positive beliefs, nonusers perceived
      negative outcomes for the care recipient with dementia or faced barriers
      associated with the recipient's behavioral or physical needs. To address negative
      perceptions, nurses may need to promote the benefits of day centers for both
      caregivers and care recipients. However, improvements in program activities and
      environments, staff development, and caregiver support are also required to
      address negative beliefs and meet the needs of those currently not accessing
      care.

PMID- 22420522
TI  - Differences in the clinical characteristics between young and elderly men with
      varicocoele.
AB  - Information concerning the clinical characteristics in elderly men with
      varicocoele is relatively limited. This study was assessed to evaluate the
      differences in clinical characteristics between young and elderly patients with
      varicocoele by retrospective chart review. Between June 2003 and February 2011,
      169 young (18-30 years) men and 156 elderly (45-55 years) men with varicocoele,
      and 30 age-matched men without varicocoele were recruited for this study. All the
      patients were divided into six groups. Thirty-one infertile patients were
      assigned to Group 1, 138 fertile patients to Group 2, 35 infertile patients to
      Group 3 and 121 fertile patients to Group 4. Group 5 (15 young) and 6 (15
      elderly) were control groups. The parameters for comparison included body mass
      index (BMI), semen quality (sperm motility, morphology and density) and pH value,
      serum concentration of follicle-stimulating hormone (FSH), luteinizing hormones
      (LH), testosterone, testicular volume, grade of varicocoele and peak retrograde
      flow (PRF) and maximal vein diameter (MVD) by colour Doppler ultrasound (CDS).
      Elderly men with varicocoele had a higher incidence of bilateral varicocoele
      (25.5% vs. 14.8%), but a lower incidence of unilateral right varicocoele (2.6%
      vs. 7.7%) than young patients with varicocoele. In addition, patients with
      varicocoele had lower BMI than those without, and infertile young patients with
      varicocoele had the lowest levels of BMI. Furthermore, infertile patients (Groups
      1 and 3) with varicocoele had significantly lower testicular volume and semen pH,
      lower levels of testosterone, higher levels of FSH and LH and higher PRF than
      fertile men with varicocoele (Groups 2 and 4). In conclusion, infertile elderly
      patients with varicocoele had significantly lower levels of testosterone and
      higher levels of FSH and LH than infertile young men with varicocoele. In
      addition, infertile elderly patients with bilateral varicocoele (Group 3, n = 8)
      had the lowest levels of testosterone.

PMID- 22420523
TI  - Mollusks of Candomble: symbolic and ritualistic importance.
AB  - Human societies utilize mollusks for myriad material and spiritual ends. An
      example of their use in a religious context is found in Brazil's African-derived
      belief systems. Candomble, an Afro-Brazilian religion introduced during the 18th
      19th centuries by enslaved Yoruba, includes various magical and liturgical uses
      of mollusks. This work inventoried the species utilized by adherents and to
      analyzed their symbolic and magical context. Data were obtained from Candomble
      temples in two cities in the northeast of Brazil-Caruaru, in the state of
      Pernambuco, and Campina Grande, in the state of Paraiba. Questionnaires
      administered to eleven adepts revealed that at least nineteen mollusk species are
      being used. Shells from Monetaria moneta, M. annulus and Erosaria caputserpentis
      were cited by all of the interviewees. Three uses stood out: divination (jogo de
      buzios); utilization as ritual objects; and employment as sacrificial offerings
      (Igbin or Boi-de-Oxala). The jogo de buzios (shell toss), employed in West
      Africa, Brazil and Cuba, is of fundamental importance to the cult, representing
      the means by which the faithful enter in contact with the divinities (Orixas) and
      consult people's futures (Odu). The utilization of mollusks in Candomble is
      strongly influenced by ancient Yoruba myths (Itas) which, having survived
      enslavement and generations of captive labor, continue to guide the lives of
      Brazil's African Diaspora.

PMID- 22420524
TI  - Ultrastructural study by backscattered electron imaging and elemental
      microanalysis of biomaterial-to-bone interface and mineral degradation of bovine
      xenografts in maxillary sinus floor elevation.
AB  - OBJECTIVES: The aim of this study was to perform an ultrastructural study of the
      bone-to-biomaterial interface and biomaterial mineral degradation in retrieved
      bone biopsies following maxillary sinus augmentation using bovine xenografts
      (Endobon((r))) in 15 clinical cases. MATERIALS AND METHODS: Nine months after
      sinus lifting, bone cores were harvested from the maxillary sinus. The specimens
      were processed for observation under a scanning electron microscope with
      backscattered electron imaging (SEM-BSE). In addition, chemical analysis and
      elemental mapping of the mineral composition were generated using a
      microanalytical system based on energy-dispersive X-ray spectrometry (EDX).
      RESULTS: No clinical complications occurred during surgery. Scanning electron
      microscopy revealed that newly formed bone was closely attached to the xenograft.
      Elemental analysis showed a significantly high Ca/P ratio in the residual
      biomaterials (3.031 +/- 0.104) compared with the interface (2.908 +/- 0.115) and
      new bone (2.889 +/- 0.113), which suggests that there may be a gradual diffusion
      of Ca ions from the biomaterial into the newly forming bone at the interface as
      part of the biomaterial's resorption process. EDX analysis of the residual bovine
      biomaterial showed particle categories with different mean Ca/P ratios according
      to size, pointing to different stages of the resorption process. CONCLUSIONS: The
      biomaterial proved to be biocompatible and osteoconductive when used as a bone
      substitute for maxillary sinus elevation. The grafting material used is not a
      completely resorbable material over the time period covered by this study.

PMID- 22420525
TI  - Long-term hepatic allograft acceptance based on CD40 blockade by ASKP1240 in
      nonhuman primates.
AB  - Blockade of the CD40-CD154 costimulatory signal is an attractive strategy for
      immunosuppression and tolerance induction in organ transplantation. Treatment
      with anti-CD154 monoclonal antibodies (mAbs) results in potent immunosuppression
      in nonhuman primates (NHPs). Despite plans for future clinical use, further
      development of these treatments was halted by complications. As an alternative
      approach, we have been focusing on the inhibition of the counter receptor, CD40
      and have shown that a novel human anti-CD40 mAb, ASKP1240, markedly prolongs
      renal allograft survival in NHPs, although allografts eventually underwent
      chronic allograft nephropathy. On the basis of our previous findings that a CD40
      CD154 costimulation blockade induces tolerance to hepatic, but not cardiac,
      allografts in rodents, we tested here our hypothesis that a blockade of CD40 by
      ASKP1240 allows acceptance of hepatic allografts in NHPs. A 2-week ASKP1240
      induction treatment prolonged liver allograft survival in NHPs; however, the
      graft function deteriorated due to chronic rejection. In contrast, a 6-month
      ASKP1240 maintenance monotherapy efficiently suppressed both cellular and humoral
      alloimmune responses and prevented rejection on the hepatic allograft. No serious
      side effects, including thromboembolic complications, were noted in the ASKP1240
      treated monkeys. We conclude that CD40 blockade by ASKP1240 would be a desirable
      immunosuppressant for clinical liver transplantation.

PMID- 22420527
TI  - Beast of Burden? Comments on the NIH Genetic Testing Registry.

PMID- 22420526
TI  - Besifloxacin ophthalmic suspension 0.6% administered twice daily for 3 days in
      the treatment of bacterial conjunctivitis in adults and children.
AB  - BACKGROUND AND OBJECTIVE: Besifloxacin ophthalmic suspension 0.6% given thrice
      daily for 5 days is safe and effective in the treatment of patients with
      bacterial conjunctivitis. This study evaluated the safety and efficacy of
      besifloxacin ophthalmic suspension 0.6% administered twice daily for 3 days
      compared with vehicle in the treatment of bacterial conjunctivitis. STUDY DESIGN:
      This was a multicenter, double-masked, randomized, vehicle-controlled, parallel
      group study. METHODS: A total of 474 patients aged >=1 year with bacterial
      conjunctivitis were randomized in a 1 : 1 ratio to receive either besifloxacin
      ophthalmic suspension 0.6% or vehicle administered twice daily for 3 days. There
      were three study visits: day 1 (the baseline visit), day 4/5 (visit 2), and day 7
      +/- 1 (visit 3). The co-primary efficacy endpoints were bacterial eradication and
      clinical resolution at day 4/5 in designated study eyes of patients with culture
      confirmed bacterial conjunctivitis. Secondary efficacy endpoints were bacterial
      eradication and clinical resolution at day 7 +/- 1, individual clinical outcomes
      of ocular discharge and bulbar conjunctival injection at all visits; and
      microbial and clinical outcomes for overall bacterial species and individual Gram
      positive and Gram-negative bacterial species at each follow-up visit. Safety
      endpoints included adverse events (AEs), changes in visual acuity and
      biomicroscopy findings at each visit, and changes in ophthalmoscopy findings at
      day 7 +/- 1. RESULTS: Bacterial eradication and clinical resolution rates were
      significantly higher in the besifloxacin group than in the vehicle group (115/135
      [85.2%] vs 77/141 [54.6%], p < 0.001, and 89/135 [65.9%] vs 62/141 [44.0%], p <
      0.001, respectively) at day 4/5. Rates of bacterial eradication continued to be
      significantly greater in the besifloxacin group (115/135 [85.2%] vs 91/141
      [64.5%], respectively; p < 0.001) at day 7 +/- 1; however, the rates of clinical
      resolution did not differ significantly between the groups (103/135 [76.3%] and
      94/141 [66.7%], p = 0.209) at this visit. Ocular discharge and bulbar
      conjunctival injection at each visit were consistent with the primary outcomes.
      Clinical resolution and bacterial eradication with Gram-positive or Gram-negative
      organisms were consistent with the overall findings. All AEs in both groups were
      of mild or moderate severity and were considered unrelated to the treatment.
      CONCLUSION: Treatment with besifloxacin ophthalmic suspension 0.6% administered
      twice daily for 3 days was effective and safe in adults and children with
      bacterial conjunctivitis. CLINICAL TRIAL REGISTRATION: Registered at
      ClinicalTrials.gov as NCT00972777.

PMID- 22420528
TI  - Provisional unicentric experience with an electronic incident reporting form in
      pediatric anesthesia.
AB  - OBJECTIVE: To present and compare with literature our experience with an
      electronic anesthesia-related incident reporting form as a quality control
      measure at Gaslini Children's Hospital over a 19-month period. METHODS: All
      events that occurred between March 2009 and September 2010 were recorded. We
      adopted an electronic reporting form included in the online recording process of
      every anesthetic procedure. Events were divided into near misses and adverse
      events. Adverse events were further divided into incidents, minor events, and
      major events. Patients were divided into three age-groups: <1, between 1 and 3,
      and >3 years. RESULTS: A total of 12,850 anesthetics were performed. Eight
      (0.06%) near misses and 108 (0.8%) adverse events were reported. Adverse events
      occurred more frequently in infants. Of 108 events, 35 (32.4%), 61 (56.5%), and
      12 (11.1%) were classified as incidents, minor, and major events, respectively.
      Of all the adverse events, 66 (61%) were respiratory, 27 (25%) organizational,
      six (5%) drug-related, four (4%) cardiocirculatory, and five (5%) miscellaneous.
      CONCLUSIONS: Infants were at the highest risk to experience adverse events.
      Although experimental electronic incident reporting proved to be feasible, there
      is reason to suspect that there was underreporting of near misses. Overreporting
      of near miss events may be enhanced by easier and more straightforward reporting
      forms as well as by better education for anesthetic providers about the
      importance of recognizing and reporting near misses.

PMID- 22420529
TI  - Eliciting cross-neutralizing antibodies in mice challenged with a dengue virus
      envelope domain III expressed in  Escherichia coli.
AB  - Dengue viruses (DENVs) are mosquito-borne infectious pathogens that pose a
      serious global public health threat, and at present, no therapy or effective
      vaccines are available. Choosing suitable units as candidates is fundamental for
      the development of a dengue subunit vaccine. Domain III of the DENV-2 E protein
      (EDIII) was chosen in the present study and expressed in  Escherichia coli  by N
      terminal fusion to a bacterial leader (pelB), and C-terminal fusion with a 6*His
      tag based on the functions of DENV structure proteins, especially the
      neutralizing epitopes on the envelope E protein. After two-step purification
      using Ni-NTA affinity and cation-exchange chromatography, the His-tagged EDIII
      was purified up to 98% homogenicity. This recombinant EDIII was able to trigger
      high levels of neutralizing antibodies in both BALB/c and C57BL/6 mice. Both the
      recombinant EDIII and its murine antibodies protected Vero cells from DENV-2
      infection. Interestingly, the recombinant EDIII provides at least partial cross
      protection against DENV-1 infection. In addition, the EDIII antibodies were able
      to protect suckling mice from virus challenge in vivo. These data suggest that a
      candidate molecule based on the small EDIII protein, which has neutralizing
      epitopes conserved among all 4 DENV serotypes, has important implications.

PMID- 22420530
TI  - Evaluation of cardiac manifestations in pediatric liver transplant candidates.
AB  - Knowledge concerning the involvement of the cardiovascular system in children
      awaiting liver transplant is limited. Therefore, no guidelines have been
      established on evaluating this group of patients for cardiac disease. This review
      examines the diverse cardiovascular manifestations of liver disease in children.
      We also discuss the available testing and its applicability in screening for
      cardiac disease in this vulnerable population.

PMID- 22420531
TI  - IgE sensitization to the fish parasite Anisakis simplex in a Norwegian
      population: a pilot study.
AB  - The reports on fish parasite Anisakis simplex allergy have increased in countries
      with high fish consumption in the last decade. In Norway, a high consumption
      country, the prevalence of immunoglobulin E (IgE) sensitization to A. simplex was
      still unknown. Thus, our objective was to investigate the sensitization
      prevalence in this country. At the Haukeland University Hospital, Bergen, Norway,
      two main groups of surplus serum samples were collected: one from newly recruited
      blood donors (BDO) and the other from the Allergy laboratory (ALL) after
      analysing IgE and IgE antibodies. The latter was divided into three series: one
      containing unsorted sera and two sorted by either Phadiatop((r)) >=0.35 kU(A)/l
      or total IgE >=1000 kU/l. The sera were analysed for total IgE and IgE antibodies
      against A. simplex, shrimp, house dust mite (HDM), cod and cross-reactive
      carbohydrates (CCDs). The prevalence of IgE sensitization to A. simplex was 2.0%,
      2.2% and 6.6% in BDO, the unsorted and Phadiatop((r)) positive serum groups,
      respectively. A considerable degree of cross-sensitization to shrimp and HDM is
      further suggested. Unspecific binding because of high total IgE or by binding to
      CCDs seemed to play a minor role. The prevalence of IgE sensitization to A.
      simplex appears to be lower in a Norwegian population than in other high fish
      consuming countries, but might still be overestimated owing to cross
      sensitization.

PMID- 22420532
TI  - Paediatric reference values for the peripheral T cell compartment.
AB  - Immunophenotyping of blood lymphocyte subpopulations is an important tool in the
      diagnosis of immunological and haematological diseases. Paediatric age-matched
      reference values have been determined for the major lymphocyte populations, but
      reliable reference values for the more recently described T lymphocyte
      subpopulations, like different types of memory T lymphocytes, recent thymic
      emigrants, regulatory T cells and CXCR5(+) helper T lymphocytes, are not
      sufficiently available yet. We determined reference values for the absolute and
      relative sizes of T lymphocyte subpopulations in healthy children using the lysed
      whole blood method, which is most often used in diagnostic procedures. When the
      absolute numbers of some or all T lymphocyte subpopulations fall outside these
      reference ranges, this may indicate disease. The reference values show the course
      of T lymphocyte development in healthy children. Absolute T lymphocyte numbers
      increase 1.4-fold during the first months of life, and after 9-15 months, they
      decrease threefold to adult values; this is mainly caused by the expansion of
      recent thymic emigrants and naive cells. Helper and cytotoxic T lymphocytes show
      the same pattern. Regulatory T cells increase in the first 5 months of life and
      then gradually decrease to adult values, although the absolute numbers remain
      small. The relative number of CXCR5(+) cells within the CD4(+) CD45RO(+) T
      lymphocytes increases during the first 6 months of life and then remains more or
      less stable around 20%.

PMID- 22420533
TI  - Retraction. Rehabilitation of the atrophic posterior maxilla using short implants
      or sinus augmentation with simultaneous standard-length implant placement: a 3
      year randomized clinical trial.

PMID- 22420534
TI  - A window of opportunity? Motor skills and perceptions of competence of children
      in kindergarten.
AB  - BACKGROUND: Our aim was to examine the relationship between motor skill
      proficiency and perceptions of competence of children in their first year of
      school. We also explored gender-based differences. FINDINGS: Participants were
      260 kindergarten children (mean age = 5y 9 m; boys = 52%) from eight schools;
      representing 78% of eligible children in those schools. Motor skills were
      measured using the Test of Gross Motor Development-2 and perceptions of physical
      competence were assessed using the Pictorial Scale of Perceived Competence and
      Social Acceptance for Young Children. Motor skill scores were generally low
      (percentile ranks ranged from 16 - 24) but perceptions of physical competence
      were positive (boys = 18.1/24.0, girls = 19.5/24.0). A MANOVA showed a
      significant overall effect for gender (Wilk's lambda = .84 with F (3, 254) =
      15.84, p < 0.001) and univariate F tests were significant for all outcome
      variables. The relationship between object control skills and perceptions of
      physical competence among girls was not significant; however all other
      correlations were modest but significant. CONCLUSIONS: Although motor skill
      levels were quite low, the children generally held positive perceptions of their
      physical competence. These positive perceptions provide a window of opportunity
      for fostering skillfulness. The modest relationships between perceptions of
      competence and motor skill proficiency suggest that the children are beginning to
      make self-judgments at a young age. Accordingly, opportunities for children to
      become and feel physically competent need to occur early in their school or
      preschool life.

PMID- 22420535
TI  - Generation of induced pluripotent stem cells from buffalo (Bubalus bubalis) fetal
      fibroblasts with buffalo defined factors.
AB  - Ectopically, expression of defined factors could reprogram mammalian somatic
      cells into induced pluripotent stem cells (iPSCs), which initiates a new strategy
      to obtain pluripotent stem cell lines. Attempts have been made to generate
      buffalo pluripotent stem cells by culturing primary germ cells or inner cell
      mass, but the efficiency is extremely low. Here, we report a successful method to
      reprogram buffalo fetal fibroblasts (BFFs) into pluripotent stem cells [buffalo
      induced pluripotent stem cell (biPSCs)] by transduction of buffalo defined
      factors (Oct4, Sox2, Klf4, and c-Myc) using retroviral vectors. The established
      biPSCs displayed typical morphological characteristics of pluripotent stem cells,
      normal karyotype, positive staining of alkaline phosphatase, and expressed
      pluripotent markers including Oct4, Sox2, Nanog, Lin28, E-Cadherin, SSEA-1, SSEA
      4, TRA-1-81, STAT3, and FOXD3. They could form embryoid bodies (EBs) in vitro and
      teratomas after injecting into the nude BALB/C mice, and 3 germ layers were
      identified in the EBs and teratomas. Methylation assay revealed that the
      promoters of Oct4 and Nanog were hypomethylated in biPSCs compared with BFFs and
      pre-biPSCs, while the promoters of Sox2 and E-Cadherin were hypomethylated in
      both BFFs and biPSCs. Further, inhibiting p53 expression by coexpression of SV40
      large T antigen and buffalo defined factors in BFFs or treating BFFs with p53
      inhibitor pifithrin-a (PFT) could increase the efficiency of biPSCs generation up
      to 3-fold, and nuclear transfer embryos reconstructed with biPSCs could develop
      to blastocysts. These results indicate that BFFs can be reprogrammed into biPSCs
      by buffalo defined factors, and the generation efficiency of biPSCs can be
      increased by inhibition of p53 expression. These efforts will provide a feasible
      approach for investigating buffalo stem cell signal pathways, establishing
      buffalo stem cell lines, and producing genetic modification buffaloes in the
      future.

PMID- 22420536
TI  - Turn-on fluorescent sensor for selective detection of Zn(2+), Cd(2+), and Hg(2+)
      in water.
AB  - A new fluorescent chemosensor based on a helical imide as fluorophore and a
      cyclen moiety as ionophore was synthesized, which not only showed enhanced
      fluorescent responses in the presence of Zn(2+), Cd(2+), and Hg(2+) but also
      could simultaneously and selectively distinguish the three cations in a simulated
      physiological condition with the help of cysteine as an auxiliary reagent.

PMID- 22420537
TI  - Adverse impact of feed channel spacers on the performance of pressure retarded
      osmosis.
AB  - This article analyzes the influence of feed channel spacers on the performance of
      pressure retarded osmosis (PRO). Unlike forward osmosis (FO), an important
      feature of PRO is the application of hydraulic pressure on the high salinity
      (draw solution) side to retard the permeating flow for energy conversion. We
      report the first observation of membrane deformation under the action of the high
      hydraulic pressure on the feed channel spacer and the resulting impact on
      membrane performance. Because of this observation, reverse osmosis and FO tests
      that are commonly used for measuring membrane transport properties (water and
      salt permeability coefficients, A and B, respectively) and the structural
      parameter (S) can no longer be considered appropriate for use in PRO analysis. To
      accurately predict the water flux as a function of applied hydraulic pressure
      difference and the resulting power density in PRO, we introduced a new
      experimental protocol that accounts for membrane deformation in a spacer-filled
      channel to determine the membrane properties (A, B, and S). PRO performance model
      predictions based on these determined A, B, and S values closely matched
      experimental data over a range of draw solution concentrations (0.5 to 2 M NaCl).
      We also showed that at high pressures feed spacers block the permeation of water
      through the membrane area in contact with the spacer, a phenomenon that we term
      the shadow effect, thereby reducing overall water flux. The implications of the
      results for power generation by PRO are evaluated and discussed.

PMID- 22420538
TI  - Effects of mechanical insufflation-exsufflation in preventing respiratory failure
      after extubation: a randomized controlled trial.
AB  - INTRODUCTION: Weaning protocols that include noninvasive ventilation (NIV)
      decrease re-intubation rates and ICU length of stay. However, impaired airway
      clearance is associated with NIV failure. Mechanical insufflation-exsufflation
      (MI-E) has been proven to be very effective in patients receiving NIV. We aimed
      to assess the efficacy of MI-E as part of an extubation protocol. METHOD:
      Patients with mechanical ventilation (MV) for more than 48 hours with specific
      inclusion criteria, who successfully tolerated a spontaneous breathing trial
      (SBT), were randomly allocated before extubation, either for (A) a conventional
      extubation protocol (control group), or (B) the MI-E extubation protocol (study
      group). During the postextubation period (48 hours), group A patients received
      standard medical treatment (SMT), including NIV in case of specific indications,
      whereas group B received the same postextubation approach plus three daily
      sessions of mechanical in-exsufflation (MI-E). Reintubation rates, ICU length of
      stay, and NIV failure rates were analyzed. RESULTS: Seventy-five patients (26
      women) with a mean age of 61.8 +/- 17.3 years were randomized to a control group
      (n = 40; mean SAPS II, 47.8 +/- 17.7) and to a study group (n = 35; mean SAPS II,
      45.0 +/- 15.0). MV time before enrollment was 9.4 +/- 4.8 and 10.5 +/- 4.1 days
      for the control and the study group, respectively. In the 48 hours after
      extubation, 20 control patients (50%) and 14 study patients (40%) used NIV. Study
      group patients had a significant lower reintubation rate than did controls; six
      patients (17%) versus 19 patients (48%), P < 0.05; respectively, and a
      significantly lower time under MV; 17.8 +/- 6.4 versus 11.7 +/- 3.5 days; P <
      0.05; respectively. Considering only the subgroup of patients that used NIV, the
      reintubation rates related to NIV failure were significantly lower in the study
      group when compared with controls; two patients (6%) versus 13 (33%); P < 0.05,
      respectively. Mean ICU length of stay after extubation was significantly lower in
      the study group when compared with controls (3.1 +/- 2.5 versus 9.8 +/- 6.7 days;
      P < 0.05). No differences were found in the total ICU length of stay. CONCLUSION:
      Inclusion of MI-E may reduce reintubation rates with consequent reduction in
      postextubation ICU length of stay. This technique seems to be efficient in
      improving the efficacy of NIV in this patient population.

PMID- 22420539
TI  - Microcephaly-lymphedema-chorioretinal dysplasia associated with pachymicrogyria
      and atrophy of the cerebellar vermis: an integration of brain-ocular migration
      disorders.
AB  - BACKGROUND: Microcephaly-lymphedema-chorioretinal dysplasia (OMIM 152950) is a
      rare malformative inherited disorder that can be associated with other systemic
      features. Other ocular and brain anomalies rather than microcephaly and
      chorioretinal dysplasia have been inconstantly reported in this syndrome.
      METHODS: We present a case of microcephaly-lymphedema-chorioretinal dysplasia
      with a dysmorphic facies, hypertonicity in the extremities and neuropsychomotor
      delay. Ophthalmological examination revealed bilateral nystagmus, microphthalmia,
      posterior subcapsular cataratacts, extensive chorioretinal dysplasia, optic nerve
      aplasia, persistent fetal vasculature, and absent retinal vessels. RESULTS:
      Magnetic resonance revealed pachymicrogyria and discrete atrophy of vermis
      cerebelosum and confirmed optic nerve hypoplasia. CONCLUSIONS: The developmental
      alterations observed in the retina of this patient could be analogous to central
      nervous system anomalies, reflecting a reduction in neural population. Ophthalmic
      examination of children with microcephaly is warranted.

PMID- 22420540
TI  - Coassembly of enantiomeric amphipathic peptides into amyloid-inspired rippled
      beta-sheet fibrils.
AB  - Amphipathic peptides composed of alternating hydrophobic and hydrophilic amino
      acids self-assemble into amyloid-inspired, beta-sheet nanoribbon fibrils. Herein,
      we report a new fibril type that is formed from equimolar mixtures of
      enantiomeric amphipathic peptides (L- and D-(FKFE)(2)). Spectroscopic analysis
      indicates that these peptides do not self-sort and assemble into enantiomeric
      fibrils composed of all-l and all-d peptides, but rather coassemble into fibrils
      that contain alternating L- and D-peptides in a "rippled beta-sheet" orientation.
      Isothermal titration calorimetry indicates an enthalpic advantage for rippled
      beta-sheet coassembly compared to self-sorted beta-sheet assembly of enantiomeric
      peptides.

PMID- 22420541
TI  - Isolation and identification of mosquito (Aedes aegypti ) biting deterrent fatty
      acids from male inflorescences of breadfruit (Artocarpus altilis (Parkinson)
      Fosberg).
AB  - Dried male inflorescences of breadfruit ( Artocarpus altilis , Moraceae) are
      burned in communities throughout Oceania to repel flying insects, including
      mosquitoes. This study was conducted to identify chemicals responsible for
      mosquito deterrence. Various crude extracts were evaluated, and the most active,
      the hydrodistillate, was used for bioassay-guided fractionation. The
      hydrodistillate and all fractions displayed significant deterrent activity.
      Exploratory GC-MS analysis revealed more than 100 distinctive peaks, and more
      than 30 compounds were putatively identified, including a mixture of terpenes,
      aldehydes, fatty acids, and aromatics. A systematic bioassay-directed study using
      adult  Aedes aegypti  females identified capric, undecanoic, and lauric acid as
      primary deterrent constituents. A synthetic mixture of fatty acids present in the
      most active fraction and individual fatty acids were all significantly more
      active than N,N-diethyl-m-toluamide (DEET). These results provide support for
      this traditional practice and indicate the potential of male breadfruit flowers
      and fatty acids as mosquito repellents.

PMID- 22420543
TI  - Preclinical testing of active substances and cancer research.

PMID- 22420542
TI  - Interspecies interactions and potential Influenza A virus risk in small swine
      farms in Peru.
AB  - BACKGROUND: The recent avian influenza epidemic in Asia and the H1N1 pandemic
      demonstrated that influenza A viruses pose a threat to global public health. The
      animal origins of the viruses confirmed the potential for interspecies
      transmission. Swine are hypothesized to be prime "mixing vessels" due to the dual
      receptivity of their trachea to human and avian strains. Additionally, avian and
      human influenza viruses have previously been isolated in swine. Therefore,
      understanding interspecies contact on smallholder swine farms and its potential
      role in the transmission of pathogens such as influenza virus is very important.
      METHODS: This qualitative study aimed to determine swine-associated interspecies
      contacts in two coastal areas of Peru. Direct observations were conducted at both
      small-scale confined and low-investment swine farms (n = 36) and in open areas
      where swine freely range during the day (n = 4). Interviews were also conducted
      with key stakeholders in swine farming. RESULTS: In both locations, the
      intermingling of swine and domestic birds was common. An unexpected contact with
      avian species was that swine were fed poultry mortality in 6/20 of the farms in
      Chancay. Human-swine contacts were common, with a higher frequency on the
      confined farms. Mixed farming of swine with chickens or ducks was observed in 36%
      of all farms. Human-avian interactions were less frequent overall. Use of
      adequate biosecurity and hygiene practices by farmers was suboptimal at both
      locations. CONCLUSIONS: Close human-animal interaction, frequent interspecies
      contacts and suboptimal biosecurity and hygiene practices pose significant risks
      of interspecies influenza virus transmission. Farmers in small-scale swine
      production systems constitute a high-risk population and need to be recognized as
      key in preventing interspecies pathogen transfer. A two-pronged prevention
      approach, which offers educational activities for swine farmers about sound
      hygiene and biosecurity practices and guidelines and education for poultry
      farmers about alternative approaches for processing poultry mortality, is
      recommended. Virological and serological surveillance for influenza viruses will
      also be critical for these human and animal populations.

PMID- 22420544
TI  - Cytotoxicity of gold(III) complexes on A549 human lung carcinoma epithelial cell
      line.
AB  - We have studied the kinetics of the complex formation of gold(III) complexes,
      [Au(en)Cl2]+ (dichlorido( ethylendiamine)aurate(III)-ion) [Au(dach)Cl2]
      (dichloride(1,2-diaminocyclohexane)aurate(III)-ion) and [Au(bipy)Cl2]+
      (dichlorido(2,2'-bipyridyl)aurate(III)-ion) with guanosine5'-monophosphate (5'
      GMP). It was shown that 5'-GMP have a high affinity for gold(III) complex, which
      may have important biological implications, since the interactions of Au(III)
      with DNA are thought to be responsible for the anti-tumor activity. The
      [Au(bipy)Cl2]+ complex is more reactive than [Au(en)Cl2]+ or [Au(dach)Cl2]+. The
      activation parameters for all studied reactions suggest an associative
      substitution mechanism. The cytotoxicity of gold(III) complexes was tested on
      A549 human lung carcinoma epithelial cell line and was evaluated by cytotoxic
      (MTT and LDH test) and apoptotic assays. The results showed that all tested
      gold(III) complexes displayed cytotoxic effect on A549 cells. Among the tested
      gold (III) complexes, AuBIPY showed the best cytotoxic effects.

PMID- 22420545
TI  - Toxic effects of palladium compounds on the isolated rat heart.
AB  - Taken into consideration limited data about effects of palladium on
      cardiovascular system, the aim of our study was to compare toxicity of inorganic
      and organic palladium compounds on the isolated rat heart. The hearts (total
      number n=30, 6 for each experimental group) excised from Wistar albino rats, male
      sex, age 8 weeks, and body mass 180-200 g, were retrogradely perfused according
      to the Langendorff technique at constant perfusion pressure (70 cm H2O). After
      the insertion of sensor in the left ventricle, the parameters of heart function:
      maximum rate of left ventricular pressure development (dP/dt max), systolic left
      ventricular pressure (SLVP), diastolic left ventricular pressure (DLVP), mean
      blood pressure (MBP) and heart rate (HR)), were continuously registered. The
      experiments were performed during control conditions, and in the presence of
      perfusion with incresing concentration of the following: (triethanolamine (TEA),
      triethanolamine acetate (TEAA), palladium(II)chloride (PdCl2), and trans
      dichlorobis(triethanolamine-N)palladium(II) complex (trans-[PdCl2(TEA)2]))
      started every 30 minutes (30, 60, 90, 120 minute). dP/dt max was not affected
      significantly by either TEAA, TEA, PdCl2 or Pd complex. SLVP was, also, not
      affected significantly by either TEAA, TEA, PdCl2, or Pd complex. DLVP was
      significantly decreased by both TEAA and PdCl2, while TEA and Pd complex did not
      show significant effect. MBP was significantly decreased only by PdCl2, while
      TEAA, TEA and Pd complex did not show significant effect. HR was significantly
      decreased by all compounds- PdCl2, TEAA, TEA and Pd complex. In our study,
      inorganic palladium compound (PdCl2) induced clear depression of the isolated rat
      heart contractility, manifested as drop in diastolic and mean blood pressure ,
      and as decrease of the heart rate. On the other hand, it seems that palladium,
      when bound in an organic compound (linked to TEA in Pd complex), does not
      contribute significantly to cardio-toxicity in our experimental conditions.

PMID- 22420546
TI  - Mechanism of pain relief by low-power infrared irradiation: ATP is an IR-target
      molecule in nociceptive neurons.
AB  - Effects of infrared (IR) radiation generated by a low-power CO2-laser on the
      membrane of cultured dissociated nociceptive neurons of newborn rat spinal
      ganglia were investigated using the whole-cell patch-clamp method. Low-power IR
      radiation diminished the voltage sensitivity of activation gating machinery of
      slow sodium channels (Na(v)1.8). Ouabain known to block both transducer and
      pumping functions of Na+,K+-ATPase eliminated IR irradiation effects. The
      molecular mechanism of interaction of CO2-laser radiation with sensory membrane
      was proposed. The primary event of this interaction is the process of energy
      absorption by ATP molecules. The transfer of vibrational energy from Na+,K+-
      ATPase-bound and vibrationally excited ATP molecules to Na+,K+-ATPase activates
      this enzyme and converts it into a signal transducer. This effect leads to a
      decrease in the voltage sensitivity of Na(v)1.8 channels. The effect of IR
      radiation was elucidated by the combined application of a very sensitive patch
      clamp method and an optical facility with a controlled CO2-laser. As a result,
      the mechanism of interaction of non-thermal low-power IR radiation with the
      nociceptive neuron membrane is suggested.

PMID- 22420547
TI  - Cytotoxic effects of chemotherapeutic drugs and heterocyclic compounds at
      application on the cells of primary culture of neuroepithelium tumors.
AB  - Neuroepithelial tumor cells were cultured in vitro. The biopsy material was taken
      from 93 children at removal of the brain tumors during neurosurgical operations.
      The individual features of the cells sensitivity of primary cultures in respect
      to protocol-approved chemotherapy drugs and changes in the Interleukin-6 (Il-6)
      level in the culture medium after the application of chemotherapy were
      established. The initial level of Il-6 exceeded 600.0 pg/ml in the cultural
      medium with histologically verified pilomyxoid astrocytoma cells, and ranged from
      100.0 to 200.0 pg/ml in the medium at cultivation of ganglioneuroblastoma and
      pilocytic astrocytoma. A decrease in the Il-6 level in the medium culture of
      primary tumors cells was observed after the application of chemotherapeutic
      agents on the cells of pilomyxoid astrocytoma, astrocytomas, and pilocytic
      desmoplastic/nodular medulloblastoma. The production of Il-6 increased after
      application of cytostatic drugs on the cells of oligoastrocytomas. A decrease in
      Il-6 level after application of Cisplatin and Methotrexate and a 5-10 fold
      increase in the level of Il-6 after application of Etoposide, Carboplatin,
      Cytarabine, and Gemcitabine were registered in the medium with
      ganglioneuroblastoma. To improve the cytotoxic action of chemotherapeutic agents,
      the combined application of cytostatics with heterocyclic compounds was carried
      out. A computer modeling of ligand-protein complexes of carbamide using the Dock
      6.4 and USF Chimera program packages was performed with molecular mechanics
      method. Special attention was drawn to the ability of several isoxazole
      heterocycles and isothiazolyl to inhibit the tyrosine kinase. It was proved in
      vitro that the joint application of chemotherapeutic agents and heterocyclic
      compounds could reduce the concentration of the cytostatic factor by 10 or more
      times, having maintained the maximum cytotoxic effect. It was assumed that the
      target amplification of cytotoxic action of chemotherapeutic agents had prospects
      for reducing toxic side effects of chemotherapy in vivo, which would be carried
      out only after the preclinical studies.

PMID- 22420548
TI  - Modulation of signal-transducing function of neuronal membrane Na+,K+-ATPase by
      endogenous ouabain and low-power infrared radiation leads to pain relief.
AB  - Effects of infrared (IR) radiation generated by a low-power Co2-laser on sensory
      neurons of chick embryos were investigated by organotypic culture method. Low
      power IR radiation firstly results in marked neurite suppressing action, probably
      induced by activation of Na+,K+-ATPase signal-transducing function. A further
      increase in energy of radiation leads to stimulation of neurite growth. We
      suggest that this effect is triggered by activation of Na+,K+-ATPase pumping
      function. Involvement of Na+,K+-ATPase in the control of the transduction process
      was proved by results obtained after application of ouabain at very low
      concentrations. Physiological significance of low-power IR radiation and effects
      of ouabain at nanomolar level was investigated in behavioral experiments
      (formalin test). It is shown that inflammatory pain induced by injection of
      formalin is relieved both due to ouabain action and after IR irradiation.

PMID- 22420549
TI  - Cytotoxic effects of glass ionomer cements on human dental pulp stem cells
      correlate with fluoride release.
AB  - OBJECTIVES: Glass ionomer cements (GICs) are commonly used as restorative
      materials. Responses to GICs differ among cell types and it is therefore of
      importance to thoroughly investigate the influence of these restorative materials
      on pulp stem cells that are potential source for dental tissue regeneration.
      Eight biomaterials were tested: Fuji I, Fuji II, Fuji VIII, Fuji IX, Fuji Plus,
      Fuji Triage, Vitrebond and Composit. We compared their cytotoxic activity on
      human dental pulp stem cells (DPSC) and correlated this activity with the content
      of Fluoride, Aluminium and Strontium ions in their eluates. METHODS: Elution
      samples of biomaterials were prepared in sterile tissue culture medium and the
      medium was tested for toxicity by an assay of cell survival/proliferation (MTT
      test) and apoptosis (Annexin V FITC Detection Kit). Concentrations of Fluoride,
      Aluminium and Strontium ions were tested by appropriate methods in the same
      eluates. RESULTS: Cell survival ranged between 79.62% (Fuji Triage) to 1.5% (Fuji
      Plus) and most dead DPSCs were in the stage of late apoptosis. Fluoride release
      correlated with cytotoxicity of GICs, while Aluminium and Strontium ions, present
      in significant amount in eluates of tested GICs did not. SIGNIFICANCE: Fuji Plus,
      Vitrebond and Fuji VIII, which released fluoride in higher quantities than other
      GICs, were highly toxic to human DPSCs. Opposite, low levels of released fluoride
      correlated to low cytotoxic effect of Composit, Fuji I and Fuji Triage.

PMID- 22420550
TI  - Biological effects, total phenolic content and flavonoid concentrations of
      fragrant yellow onion (Allium flavum L.).
AB  - The antioxidant, antibacterial and antiproliferative activities, total phenolic
      content and concentrations of flavonoids of A. flavum extracts were determined.
      The total phenolic content was determined with Folin-Ciocalteu reagent and it
      ranged between 42.29 to 80.92 mg GA/g. The concentration of flavonoids in various
      extracts of A. flavum was determined using spectrophotometric method with
      aluminum chloride and obtained results varied from 64.07 to 95.71 mg RU/g. The
      antioxidant activity was monitored spectrophotometrically and expressed in terms
      of IC50 (MUg/ml), and its values ranged from 64.34 to 243.34 MUg/ml. The highest
      phenolic content and capacity to neutralize DPPH radicals were found in acetone
      extract. Antibacterial efficacy was defined by determining minimum inhibitory and
      minimum bactericidal concentrations using microdilution method. Significant
      antibacterial activity, especially for ethyl acetate extract, was observed. The
      best activity was showed against G+ bacteria, Staphylococcus aureus ATCC 25923
      and Bacillus subtilis, while Escherichia coli was one of the least sensitive
      bacteria. Antiproliferative activity of the methanolic extract on HCT- 116 cell
      line was determined by MTT assay. Results showed that A. flavum has good
      antiproliferative activity with IC50 values of 28.29 for 24 h and 35.09 for 72 h.
      Based on these results, A. flavum is a potential source of phenols as natural
      antioxidant, antibacterial and anticancer substance of high value. Phenolic
      content of extracts depend on the solvents used for extraction.

PMID- 22420551
TI  - Different sensitivity of various brain structures to thioacetamide-induced lipid
      peroxidation.
AB  - Thioacetamide (TAA) exerts hepatotoxic, neurotoxic and carcinogenic effects. The
      aim of our study was to investigate the effects of TAA on lipid peroxidation and
      catalase activity in various rat brain regions. Male Wistar rats were divided
      into following groups: 1. control, saline-treated; 2. thioacetamide-treated
      groups, TAA300 (300 mg/kg), TAA600 (600 mg/kg) and TAA900 (900 mg/kg). Daily dose
      of TAA (300 mg/kg) was administered intraperitoneally once (TAA300), twice
      (TAA600) and three times (TAA900) in consecutive days. Brain samples were
      collected 24 h after the last dose of TAA and malondialdehyde (MDA) level and
      catalase activity were determined in cortex, brainstem and hippocampus. MDA level
      was significantly increased while catalase activity was significantly lower in
      all brain regions in TAA900 group in comparison with control group. In TAA600 MDA
      level was increased in the brainstem and cortex when compared to control (p <
      0.01). The same dose of TAA 600 mg/kg induced a significant decline in catalase
      activity in the brainstem and cortex and an increase in its activity in the
      hippocampus when compared to control (p < 0.01). In TAA300 an increase in MDA
      level was evident only in the brainstem. Catalase activity was significantly
      higher in the cortex and hippocampus in TAA300 group in comparison with control
      (p < 0.01). Based on these results, it may be concluded that various rat brain
      regions have different sensitivity to TAA-induced lipid peroxidation with
      hippocampus being less sensitive than cerebral cortex and brainstem.

PMID- 22420552
TI  - Inhibition of the neuronal nitric oxide synthase potentiates homocysteine
      thiolactone-induced seizures in adult rats.
AB  - Nitric oxide (NO), one of the gaseous neurotransmitters, is produced in reaction
      catalyzed by family of NO synthases (NOS). The involvement of neuronal NOS (nNOS)
      in seizures induced by homocysteine thiolactone has not been studied. Therefore,
      the aim of this study was to determine the effects of 7-nitroindazole, a
      selective nNOS inhibitor, on behavioral manifestations of homocysteine - induced
      seizures in adult rats. Adult male Wistar albino rats were treated with 7
      nitroindazole (25, 50 and 75 mg/kg, i.p.) 30 min before injection of
      subconvulsive dose of homocysteine (D,L homocysteine thiolactone 5.5 mmol/kg,
      i.p.). Convulsive behavior was assessed during 90 min upon homocysteine
      administration by the following parameters: seizure incidence, duration of
      latency, number of seizure episodes per rat and their severity. Severity of
      seizures was evaluated using a descriptive scale graded from 0 to 4. It was shown
      that 7-nitroindazole increased seizure incidence, shortened latency time to first
      seizure, increased number of seizure episodes per rat and increased severity of
      seizures induced by homocysteine in rats. 7- nitroindazole in dose of 25 mg/kg
      led to a statistically significant increase in the seizure incidence and number
      of seizure episodes per rat, while doses of 50 and 75 mg/kg significantly
      increased severity of homocysteine-induced seizures. It could be concluded that
      inhibition of nNOS by 7-nitroindazole potentiates seizures induced by
      homocysteine in rats.

PMID- 22420553
TI  - Effect of cellular cholesterol changes on insulin secretion by tumor cell lines.
AB  - Glucose and cell swelling induce insulin secretion by alternative signaling
      pathways. Swelling-induced secretion is in most systems independent of calcium
      and various mediators of glucose stimulation. Comparison of two insulinoma tumor
      cell lines revealed surprising difference; INS-1E cells in contrast to INS-1
      cells and isolated rat pancreatic islets do not respond to hypotonicity in the
      presence of calcium. To delineate the role of cholesterol the effect of its
      extraction or addition on the insulin secretion in response to glucose and cell
      swelling was compared. INS-1E cells have significantly higher cholesterol content
      than INS-1 cells (58.5 +/- 2.9 and 46.3 +/- 2.5 mg chol/mg prot respectively).
      After cholesterol desorption by 1.0, 5.0 and 10.0 mM of carboxymethyl-beta
      cyclodextrin, methyl-beta-cyclodextrin, or 2-hydroxypropyl-beta- cyclodextrin the
      response to hypotonicity in INS-1E cells emerged. On the contrary,
      supplementation of INS-1 cells with cholesterol inhibited their response to cell
      swelling. Cyclodextrin pretreatment inhibited glucose-induced insulin secretion
      from INS-1 cells while INS-1E cells were more resistant to their effect.
      CONCLUSION: Cellular cholesterol content substantially affects secretory process;
      both high and low levels could be inhibitory. Absence of swelling-induced insulin
      secretion in INS-1E cells despite adequate response to glucose is related to
      their high cholesterol content. Optimal cholesterol concentration is different
      for either type of stimulation; swelling-induced mechanism is more sensitive to
      higher cholesterol content. The difference is likely to reflect involvement of
      sequential type exocytosis after cell swelling. Sensitivity of secretory
      processes suggests that either hypercholesterolemia or excessive effort to
      decrease plasma cholesterol in patients could have adverse effect on insulin
      secretion.

PMID- 22420554
TI  - Thin-layer chromatography with biodetection for the screening of natural origin
      samples.

PMID- 22420555
TI  - BioArena studies: unique function of endogenous formaldehyde and ozone in the
      antibiotic effect--a review.
AB  - The investigations demonstrated clearly a unique function and role of endogenous
      formaldehyde (HCHO) and ozone (O3) in the antibiotic effect of diverse molecules
      having different chemical structure. Elimination of HCHO and/or O3 from the layer
      chromatographic spots resulted in a decrease in the antimicrobial activity. On
      the basis of detection and measure of endogenous HCHO and O3 BioArena enables to
      both direct isolation and biological evaluation of new bioactive compounds.

PMID- 22420556
TI  - Separation and identification of antibacterial chamomile components using OPLC,
      bioautography and GC-MS.
AB  - Components of 50% aqueous ethanol chamomile (Matricaria recutica L.) flower
      extract, previously found antibacterial in a TLC-bioautographic study, were
      separated and isolated by the use of on-line overpressured layer chromatography
      (OPLC). This system consisted of an OPLC 50 BS system, an on-line coupled flow
      through UV detector, and a manual fraction collector. The collected fractions
      were investigated by GC-MS analysis and by TLC re-chromatography with subsequent
      visualization, performed after use of the vanillin-sulphuric acid reagent, or
      under UV illumination, or applying bioautographic detection. The main compounds
      of the collected 11 fractions were identified by GC-MS. The results showed that
      the antibacterial effect of 50% aqueous ethanol extract of chamomile is
      ascribable to cis-, trans-spiroethers, and the coumarins like herniarin and
      umbelliferone.

PMID- 22420557
TI  - Comparison of deproteinization methods used before TLC-DB and HPLC analysis of
      flumequine residues in milk.
AB  - Seventeen various extraction procedures based on precipitation of proteins in
      milk samples spiked with flumequine were tested. Several criteria were taken into
      account, when choosing the most effective. The supernatants were analyzed by thin
      layer chromatography direct bioautography (TLC-DB) and high performance liquid
      chromatography (HPLC-UV). The results obtained from both methods indicate as the
      best the same deproteinization procedure. The addition of acetonitrile to milk in
      1:1 volume proportions gave the highest concentration of flumequine in
      supernatant and prompt coagulation of proteins in milk samples.

PMID- 22420558
TI  - Thin-layer chromatography with biodetection in the search for new potential drugs
      to treat neurodegenerative diseases--state of the art and future perspectives.
AB  - This paper summarizes the application of thin-layer chromatography coupled with
      biodetection for the search of substances characterized with properties relevant
      to the treatment of neurodegenerative diseases. The main focus is on the
      screening of plant extracts for the presence of acetycholinesterase inhibitors as
      well as direct antioxidants, taking into account the cholinergic hypothesis of
      Alzheimer's disease and oxidative stress theory of neurodegeneration. Practical
      aspects of performing TLC-bioassay tests are discussed and typical problems are
      addressed. Some practical hints are also given referring to the variety of
      compound classes that may be analyzed by means of these methods.

PMID- 22420559
TI  - Discovery of beta-glucosidase inhibitors from a chemically engineered extract
      prepared through ethanolysis.
AB  - A series of vegetal extracts have been chemically altered by ethanolysis. The
      effect of the reaction on the inhibition of the enzyme beta-glucosidase
      properties of the mixtures was studied using thin layer chromatography (TLC) with
      biodetection. Glucosidase inhibitory activity guided fractionation of one of the
      produced chemically engineered extracts led to the isolation of apigenin and
      ethyl p-cumarate. Both compounds were generated during the chemical modification
      step.

PMID- 22420560
TI  - Two-dimensional thin layer chromatographic separation of phenolic compounds from
      Eupatorium cannabinum extracts and their antioxidant activity.
AB  - Two dimensional thin layer chromatography on DIOL polar bonded stationary phase
      was performed to optimize the separation of some anioxidant phenolic compounds
      from Eupatorium cannabinum extracts. Ethyl-methyl ketone mixed with n-heptane and
      ethyl acetate mixed with n-heptane were used as non-aqueous mobile phases in
      normal phase separations (1st direction of development in 2D-HPTLC mode) and
      methanol mixed with water was used as a mobile phase in reversed phase (2nd
      direction of development in 2D-HPTLC mode). The plates were sprayed by use of
      Merck TLC sprayer using 2-(diphenylboryoxy)-ethylamine and PEG4000 (Merck,
      Darmstadt, Germany) or DPPH and photographed in Camag Cabinet UV lamp at 254 nm
      and 365 nm by use of Fuji 8 mpx camera. Satisfactory separations of antioxidant
      phenolic compounds in Eupatorium cannabinum extracts were obtained by use of
      optimized 2D-HPTLC systems.

PMID- 22420561
TI  - Medicinal Chemistry. Foreword.

PMID- 22420562
TI  - Comparison of different anaesthetic methodologies for sedation during in vitro
      fertilization procedures: effects on patient physiology and oocyte competence.
AB  - The main goal of the present retrospective study is to compare four analgesic
      methodologies (EMLA cream, propofol, thiopental sodium, sevoflurane) for in vitro
      fertilization (IVF) oocyte retrieval. We found that most anaesthetic parameters
      were not significantly different among all treatments. In contrast, significant
      differences were revealed in all groups for total number of oocytes retrieved per
      patient, rate of mature oocytes at metaphase II stage (MII) and percentage of
      fertilization and embryo development. In the EMLA cream and thiopental sodium
      groups we observed the highest percentage of MII oocytes (P < 0.001).
      Fertilization rate in the EMLA and sevoflurane groups were similar but
      significantly higher than the propofol and thiopental sodium groups (P < 0.001).
      The highest rate of anomalous fertilization was observed in the propofol group.
      Rate of embryo development was similar in all groups but sevoflurane group had a
      lower percentage of good embryos. In conclusion, by comparing different
      anaesthetic techniques with different mechanisms of action and administration,
      potential negative effects of these drugs on the initial stages of human IVF
      procedure were revealed. Therefore, a local anaesthetic cream is proposed as an
      acceptable alternative option for anaesthesia during transvaginal oocyte
      retrieval.

PMID- 22420563
TI  - Reduction of pesticide residues on fresh vegetables with electrolyzed water
      treatment.
AB  - Degradation of the 3 pesticides (acephate, omethoate, and dimethyl dichloroviny
      phosphate [DDVP]) by electrolyzed water was investigated. These pesticides were
      commonly used as broad-spectrum insecticides in pest control and high-residual
      levels had been detected in vegetables. Our research showed that the electrolyzed
      oxidizing (EO) water (pH 2.3, available chlorine concentration:70 ppm, oxidation
      reduction potential [ORP]: 1170 mV) and the electrolyzed reducing (ER) water (pH
      11.6, ORP: -860 mV) can reduce the pesticide residues effectively. Pesticide
      residues on fresh spinach after 30 min of immersion in electrolyzed water reduced
      acephate by 74% (EO) and 86% (ER), omethoate by 62% (EO) and 75% (ER), DDVP by
      59% (EO) and 46% (ER), respectively. The efficacy of using EO water or ER water
      was found to be better than that of using tap water or detergent (both were
      reduced by more than 25%). Besides spinach, the cabbage and leek polluted by DDVP
      were also investigated and the degradation efficacies were similar to the
      spinach. Moreover, we found that the residual level of pesticide residue
      decreased with prolonged immersion time. Using EO or ER water to wash the
      vegetables did not affect the contents of Vitamin C, which inferred that the
      applications of EO or ER water to wash the vegetables would not result in loss of
      nutrition.

PMID- 22420564
TI  - Effects of inducible nitric oxide synthase (iNOS) deficiency in mice on Sertoli
      cell proliferation and perinatal testis development.
AB  - Nitric oxide (NO) plays crucial roles in several physiological and pathological
      conditions. The iNOS isoform produces high levels of NO independent of
      intracellular calcium and, in the testis, which is expressed in Sertoli (SC),
      Leydig (LC) and germ cells. The testicular roles of NO are unclear, but it can
      inhibit LC testosterone production. Our aim was to evaluate the effects of iNOS
      deficiency on testis development in mice from late fetal life through early
      puberty. Therefore, testes from wild type (C57BCL/6) and iNOS(-/-) mice (B6.129P2
      Nos2(tm1Lau) /J) were sampled at various ages between e18.5 and Pnd20 and
      evaluated by histological and stereological analyses; proliferating cells were
      labelled with (3)H-thymidine. At all ages, testis weight and anogenital index, a
      measure of fetal androgen exposure, were greater in iNOS-deficient mice than in
      wild type mice. At all ages after birth, iNOS-deficient mice exhibited increased
      (p < 0.05) SC number per testis, and this was accounted for by a higher SC
      proliferation index (p < 0.05) in iNOS-deficient mice, especially on Pnd1 and
      Pnd5. Similarly, LC number per testis was higher (p < 0.05) in iNOS(-/-) mice
      than in wild type at all post-natal ages. Highly positive and significant
      correlations were observed between the proliferation index for SC, LC and
      peritubular myoid cells on e18.5 and post-natally. Although lumen formation was
      slightly advanced in iNOS(-/-) mice, no obvious other effects on pubertal testis
      development were observed. These results imply that NO may normally constrain
      testis somatic cell development, especially SC, perhaps by limiting testosterone
      production. Removal of this constraint results in normal, but larger, testes with
      greater sperm production. Our data pinpoint the window of iNOS (NO) action on SC
      proliferation and raise the possibility that experimental manipulation of NO in
      early post-natal life could be used to enhance SC proliferation if this was
      deficient for any reason.

PMID- 22420565
TI  - A new technique for testing distribution of knowledge and to estimate sampling
      sufficiency in ethnobiology studies.
AB  - BACKGROUND: We propose a new quantitative measure that enables the researcher to
      make decisions and test hypotheses about the distribution of knowledge in a
      community and estimate the richness and sharing of information among informants.
      In our study, this measure has two levels of analysis: intracultural and
      intrafamily. METHODS: Using data collected in northeastern Brazil, we evaluated
      how these new estimators of richness and sharing behave for different categories
      of use. RESULTS: We observed trends in the distribution of the characteristics of
      informants. We were also able to evaluate how outliers interfere with these
      analyses and how other analyses may be conducted using these indices, such as
      determining the distance between the knowledge of a community and that of
      experts, as well as exhibiting the importance of these individuals' communal
      information of biological resources. One of the primary applications of these
      indices is to supply the researcher with an objective tool to evaluate the scope
      and behavior of the collected data.

PMID- 22420566
TI  - Does HRT increase the risk of breast cancer? Don't forget the menopausal woman!

PMID- 22420567
TI  - Climacteric commentaries. Calcium and vitamin D in heart disease.

PMID- 22420568
TI  - Vertical bone augmentation using different osteoconductive scaffolds combined
      with barrier domes in the rat calvarium.
AB  - PURPOSE: To compare the regenerative potential for vertical bone augmentation of
      various osteoconductive scaffolds when used in conjunction with barrier domes.
      MATERIALS AND METHODS: Following exposure and perforation of the calvarium, a
      gold occlusive dome was filled with the tested scaffold and anchored by fixation
      screws. Flaps were repositioned and secured. The four treatment groups, three to
      five rats each, were as follows: Bio-Oss collagen (BOC), beta-tricalcium
      phosphate (TCP), collagen sponge (COL), and empty domes (C). Rats were sacrificed
      8 weeks later, and specimens were prepared for histological and histomorphometric
      analysis. Vertical bone height and total tissue height were measured. RESULTS:
      The newly regenerated bone appeared mature, highly vascularized, and with no
      signs of inflammation. Vertical bone height in the TCP group (mean 2.04 +/- 0.2
      mm) was greater than all other groups (0.76 +/- 0.02, 1.52 +/- 0.18, and 1.77 +/-
      0.61 mm for the BOC, C, and COL, respectively) but significantly only for the BOC
      group (p = .0145). Total tissue height was significantly higher (p < .0001) in
      both BOC and TCP groups (4.48 +/- 0.23 and 5.5 +/- 0.24 mm, respectively)
      compared with COL (3.22 +/- 0.11 mm) and C (2.39 +/- 0.3 mm) groups. CONCLUSION:
      TCP in conjunction with barrier dome resulted in greater vertical bone
      augmentation in the calvarium of rats.

PMID- 22420569
TI  - Discovery of MAO-B inhibitors - present status and future directions part I:
      oxygen heterocycles and analogs.
AB  - Parkinson's disease (PD) is one of the most common neurodegenerative disorders.
      The role of monoamine oxidase (MAO) inhibitors has expanded in the PD treatment.
      The present review will summarize the current structureactivity relationship
      information available on MAOs inhibitors of unrelated families of compounds of
      oxygen heterocyclic type based on coumarin, chromone and chalcone scaffolds. As
      the current hitting-one-target therapeutic strategy has been proved to be quite
      inefficient in PD, this review will also discuss about the development of multi
      target drugs, in which MAO inhibition plays a counter-part, as a novel and
      promising treatment approach for PD.

PMID- 22420570
TI  - Desirability-based multi-objective QSAR in drug discovery.
AB  - The adjustment of multiple criteria in hit-to-lead identification and lead
      optimization is a major advance in drug discovery. Thus, the development of
      approaches able to handle additional criteria for the early simultaneous
      treatment of the most important properties determining the pharmaceutical profile
      of a drug candidate is an emergent issue in this area. In this paper, we review a
      desirability-based multi-objective QSAR method allowing the joint handling of
      multiple properties of interest in drug discovery: the MOOP-DESIRE methodology.
      This methodology adapts desirability theory concepts allowing the holistic
      modeling of the many and conflicting biological properties determining the
      therapeutic utility of a drug candidate. Here we survey their suitability for key
      tasks involving the use of chemoinformatics methods in medicinal chemistry and
      drug discovery.

PMID- 22420572
TI  - Monoamino oxidase a: an interesting pharmacological target for the development of
      multi-target QSAR.
AB  - With the significant increase of life expectancy of populations in societies
      today, the importance of the discovery of drugs associated with neurodegenerative
      diseases has emerged. Therefore, neurodegenerative diseases are an important
      topic in Medicinal Chemistry. Although drug discovery is considered a complex and
      slow process, new approaches and methods have been developed with the intention
      of finding new chemical entities in more efficient ways. This work provides a
      review of virtual methodologies applied in drug discovery and especially a new
      model for the prediction of MAO-A inhibitors using a multi-target QSAR
      methodology. This model involves a mixed approach containing simple descriptors
      based on atom-centered fragments and functional groups (DRAGON) and topological
      substructural molecular design descriptors (MODESLAB). This unified multi-species
      QSAR model was validated through a virtual screening of a new series of
      oxoisoaporphine derivatives, taking into account the information in the
      calculated fragmental contributions. Therefore, this method represents a useful
      tool for the in silico screening of MAO-A inhibitors.

PMID- 22420573
TI  - Multi-objective optimization methods in de novo drug design.
AB  - De-novo drug design (DND) is a complex procedure, requiring the satisfaction of
      many pharmaceutically important objectives. Several computational methodologies
      employing various optimization approaches have been developed to search for
      satisfactory solutions to this multi-objective problem varying from composite
      methods, which transform the problem to a single objective one to Pareto methods
      searching for numerous solutions compromising the objectives. In this review we
      initially focus on the DND problem and the challenges it poses to computational
      methods, followed by an examination of the reported methodologies and specific
      applications. Emphasis is placed on the multiobjective nature of the problem,
      related considerations and the solutions proposed by the drug discovery
      community.

PMID- 22420574
TI  - CNS drug development - lost in translation?
AB  - CNS drug development is characterized by an especially high attrition rate,
      despite clear unmet medical needs in the field of neuro-pharmacology and
      significant investment in R of novel CNS drug treatments. Here, we overview the
      issues underlying the intrinsic difficulty of CNS drugs development, including
      obstacles of pharmacokinetic nature and lack of predictivity of preclinical
      tests. We highlight current efforts to overcome these limitations, with an
      emphasis on modeling opportunities towards early recognition of CNS candidates
      (stressing the possibilities of multi-target directed ligands or "magic
      shotguns") and different approaches to improve CNS bioavailability.

PMID- 22420575
TI  - Recent advances in computational studies on influenza a virus M2 proton channel.
AB  - The matrix protein 2 of the influenza A virus (M2 or AM2) is one of the important
      components of the viral membrane. This protein can form a proton channel in the
      viral envelope. Owing to its ability to regulate the surrounding pH in endosome,
      this protein is an attractive target for drug design against influenza A virus.
      In this minireview, we summarized the current progresses in computational
      approaches for studying the M2 proton channel. The attention is focused on how
      protons are conducted through the M2 channel, and how adamantane-based drugs
      inhibit the channel, as well as how the drug resistance occurs, in hope to
      further stimulate the in-depth studies of this important area, both
      experimentally and theoretically.

PMID- 22420576
TI  - Status of metal contamination in surface waters of the coastal ocean off Los
      Angeles, California since the implementation of the Clean Water Act.
AB  - In order to establish the status of metal contamination in surface waters in the
      coastal ocean off Los Angeles, California, we determined their dissolved and
      particulate pools and compared them with levels reported in the 1970s prior the
      implementation of the Clean Water Act. These measurements revealed a significant
      reduction in particulate toxic metal concentrations in the last 33 years with
      decreases of ~100-fold for Pb and ~400-fold for Cu and Cd. Despite these
      reductions, the source of particulate metals appears to be primarily
      anthropogenic as enrichment factors were orders of magnitude above what is
      considered background crustal levels. Overall, dissolved trace metal
      concentrations in the Los Angeles coastal waters were remarkably low with values
      in the same range as those measured in a pristine coastal environment off
      Mexico's Baja California peninsula. In order to estimate the impact of metal
      contamination on regional phytoplankton, the internalization rate of trace metals
      in a locally isolated phytoplankton model organism (Synechococcus sp. CC9311) was
      also determined showing a rapid internalization (in the order of a few hours) for
      many trace metals (e.g., Ag, Cd, Cu, Pb) suggesting that those metals could
      potentially be incorporated into the local food webs.

PMID- 22420578
TI  - Effect of molecular weight and substitution on tissue uptake of hydroxyethyl
      starch: a meta-analysis of clinical studies.
AB  - BACKGROUND: Intravenously infused hydroxyethyl starch (HES) can be found in
      urine, plasma and tissues. HES remaining in plasma and tissues is thought to
      increase the risk of clinical complications. HES solutions of lower molecular
      weight and substitution have been developed to increase urinary excretion and
      reduce plasma persistence. However, their effect on tissue uptake of HES has not
      been investigated in human subjects. OBJECTIVE: Our objective was to test the
      hypothesis that lower molecular weight and substitution decrease tissue uptake of
      HES. DATA SOURCES: Computer searches were performed of MEDLINE; EMBASE; the
      Cochrane Library; meeting abstract databases in surgery, anaesthesiology and
      intensive care; ClinicalTrials.gov; and Google. Supplementary sources were
      reference lists and electronic tables of journal contents. No time period or
      language restrictions were imposed. STUDY SELECTION: Clinical studies were
      eligible for inclusion in the meta-analysis, if data were reported both for
      cumulative urinary excretion of HES over 24 hours after infusion and for plasma
      HES concentration at 24 hours. DATA EXTRACTION: Data were extracted on 24-hour
      urinary excretion of HES, 24-hour HES plasma concentration, plasma volume, HES
      molecular weight and substitution, study design, type and demographics of
      subjects, indication for fluid infusion, and HES infusion regimen. Tissue uptake
      of HES was computed as the difference between the infused dose and the sum of
      urinary excretion and residual plasma HES at 24 hours. DATA SYNTHESIS: Twenty
      five clinical studies totalling 287 subjects were included. Tissue uptake of low
      molecular-weight HES (<=200 kD) was 42.3% (95% confidence interval [CI] 39.6,
      45.0) compared with 24.6% (CI 17.8, 31.4) for high-molecular-weight HES (p <
      0.001). Similarly, tissue uptake of lower-substitution HES (<=0.5) was 42.4% (CI
      39.5, 45.3) versus 26.6% (CI 19.6, 33.6) for higher-substitution HES (p < 0.001).
      Among the three most often investigated single HES solutions, tissue uptake of
      130/0.4 (42.6%; CI 35.0, 50.2) and HES 200/0.5 (43.3%; CI 39.4, 47.2) closely
      coincided, whereas uptake of HES 450/0.7 (22.2%; CI 14.8, 29.6) was lower (p =
      0.001 and p < 0.001, respectively). CONCLUSIONS: This meta-analysis did not
      support the hypothesis that lower molecular weight and substitution decrease
      tissue uptake of HES. Further clinical studies of HES tissue uptake are needed.

PMID- 22420577
TI  - Pharmacokinetics and pharmacodynamics of intraperitoneal cancer
      chemotherapeutics.
AB  - Peritoneal carcinomatosis remains a significant cause of morbidity and is a
      marker of poor prognosis in a range of malignancies, including those of the
      gastrointestinal and gynaecological tracts. In these cases, regional therapy has
      been explored as a treatment strategy to take advantage of the prolonged
      confinement of such tumours within the peritoneal cavity and the steep dose
      response relationship for most cytotoxic agents. The pharmacokinetic rationale is
      based on exploiting the peritoneal-plasma barrier, which slows the rate of drug
      clearance from the peritoneal to systemic compartments and creates a
      concentration differential in favour of the peritoneal cavity. This allows higher
      drug concentrations, and thus increased cytotoxicity, to be achieved at the site
      of a tumour within the peritoneal cavity. There is pharmacodynamic evidence from
      a number of clinical trials to support the translation of these pharmacokinetic
      advantages of intraperitoneal chemotherapy into clinical benefit. However, its
      clinical application remains controversial because of concerns regarding
      intraperitoneal drug distribution, technical challenges and toxicity associated
      with regional drug delivery and the clinical relevance of the studies undertaken.
      The purpose of this review is to summarize the pharmacokinetic rationale of
      intraperitoneal drug delivery, review the pharmacodynamic studies performed in
      ovarian, colorectal and gastric cancers, and outline the future directions and
      challenges in the clinical application of this mode of treatment.

PMID- 22420579
TI  - Population pharmacokinetic analysis of denosumab in patients with bone metastases
      from solid tumours.
AB  - BACKGROUND AND OBJECTIVE: Denosumab (XGEVA(r); AMG 162) is a fully human IgG2
      monoclonal antibody, which binds to the receptor activator of nuclear factor
      kappa-B ligand (RANKL) and prevents terminal differentiation, activation and
      survival of osteoclasts. We aimed to characterize the population pharmacokinetics
      of denosumab in patients with advanced solid tumours and bone metastases.
      METHODS: A total of 14 228 free serum concentrations of denosumab from 1076
      subjects (495 healthy subjects and 581 advanced cancer patients with solid
      tumours and bone metastases) included in 14 clinical studies were pooled.
      Denosumab was administered as either single intravenous (n = 36), single
      subcutaneous (n = 490) or multiple subcutaneous doses (n = 550) ranging from 30
      to 180 mg (or from 0.01 to 3 mg/kg) and was given every 4 or 12 weeks for up to 3
      years. An open two-compartment pharmacokinetic model with first-order absorption,
      linear distribution to a peripheral compartment, linear clearance and quasi
      steady-state approximation of the target-mediated drug disposition was used to
      describe denosumab pharmacokinetics, using NONMEM Version 7.1.0 software. The
      influence of covariates (body weight, age, race, tumour type) was investigated
      using the full model approach. Model evaluation was performed through visual
      predictive checks. Model-based simulations were conducted to explore the role of
      covariates on denosumab serum concentrations and inferred RANKL occupancy.
      RESULTS: After subcutaneous administration, the dose-independent bioavailability
      and mean absorption half-life of denosumab were estimated to be 61% and 2.7 days,
      respectively. The central volume of distribution and linear clearance were 2.62
      L/66 kg and 3.25 mL/h/66 kg, respectively. Clearance and volume parameters were
      proportional to body weight. Assuming 1 : 1 denosumab-RANKL binding, the baseline
      RANKL level, quasi-steady-state constant and RANKL degradation rate were inferred
      to be 4.46 nmol/L, 208 ng/mL and 0.00116 h-1, respectively. Between-subject
      variability in model parameters was moderate. Following 120 mg dosing every 4
      weeks, the inferred RANKL occupancy at steady state exceeded 97% during the
      entire dosing interval in more than 95% of subjects, regardless of the patient
      covariates. CONCLUSIONS: The integration of pharmacokinetic data from 14 clinical
      studies demonstrated denosumab RANKL-mediated pharmacokinetics. Pharmacokinetics
      based dosage adjustments on the basis of body weight, age, race and tumour type
      are not necessary in patients with bone metastases from solid tumours.

PMID- 22420580
TI  - Modelling and simulation of the Positive and Negative Syndrome Scale (PANSS) time
      course and dropout hazard in placebo arms of schizophrenia clinical trials.
AB  - BACKGROUND AND OBJECTIVES: The likelihood of detecting a therapeutic signal of an
      effective drug for schizophrenia is impeded by a high placebo effect and by high
      dropout of patients. Several unsuccessful trials of schizophrenia, at least
      partly due to highly variable placebo effects, have indicated the necessity for a
      robust methodology to evaluate such a placebo effect and reasons for dropout.
      Hence, the objectives of this analysis were to (i) develop a longitudinal placebo
      model that accounts for dropouts and predictors of the placebo effect, using the
      Positive and Negative Syndrome Scale (PANSS) score; (ii) compare the performance
      of empirical and semi-mechanistic placebo models; and (iii) compare different
      time-to-event (TTE) dropout modelling approaches used to account for dropouts.
      METHODS: The PANSS scores from 1436 individual patients were used to develop and
      validate a placebo model. This pooled dataset included 16 trials (conducted
      between 1989 and 2009), with different study durations, in both acute and chronic
      schizophrenic patients. A nonlinear mixed-effects modelling approach was
      employed, using NONMEM VII software. RESULTS: Among the different tested placebo
      models, the Weibull model and the indirect response model adequately described
      the PANSS data. Covariate analysis showed that the disease condition, study
      duration, study year, geographic region where the trial was conducted, and route
      of administration were important predictors for the placebo effect. All three
      parametric TTE dropout models, namely the exponential, Weibull and Gompertz
      models, described the probability of patients dropping out from a clinical trial
      equally well. The study duration and trial phase were found to be predictors for
      high dropout rates. Results of joint modelling of the placebo effect and dropouts
      indicated that the probability of patients dropping out is associated with an
      observed high PANSS score. The indirect response model was found to be a slightly
      better model than the Weibull placebo model to describe the time course of the
      PANSS score. CONCLUSIONS: Our modelling approach was shown to adequately simulate
      the longitudinal PANSS data and the dropout trends after placebo treatment. Data
      analyses suggest that the Weibull and indirect response models are more robust
      than other placebo models to describe the nonlinear trends in the PANSS score.
      The developed placebo models, accounting for dropouts and predictors of the
      placebo effect, could be a useful tool in the evaluation of new trial designs and
      for better quantification of antipsychotic drug effects.

PMID- 22420581
TI  - The molecular legacy of apoptosis in transplantation.
AB  - Transplanted organs have to cope with diverse immunologic and metabolic stressors
      that augment the percentage of stressed and dying cells. Cell death, whether
      apoptotic or necrotic, is crucial in various transplantation-associated
      conditions. Necrosis, a proinflammatory type of cell death classically considered
      as accidental, is increasingly recognized as a highly controlled death program.
      Apoptosis, the classical programmed cell death mode program, is tightly
      orchestrated and culminates in the activation of caspases. Apoptosis was
      classically regarded as a silent form of cell death, but mounting evidence
      indicates that apoptotic cells "don't go silently" and leave a heritage to the
      local microenvironment. This apoptotic legacy, embedded within the effector phase
      of apoptosis, is aimed, at least in part, at controlling leukocyte trafficking
      and fostering tissue remodeling at sites of apoptotic cell deletion and can
      promote maladaptive remodeling pathways of importance for obliterative vascular
      remodeling. Moreover, apoptotic cells can transfer bioactive molecules by the
      release of apoptotic membrane vesicles that, in turn, shapes the phenotype and
      functions of immune cells. In this review, we summarize recent data highlighting
      the importance of apoptosis-associated intercellular communication networks in
      the regulation of allograft remodeling and immune responses in transplantation.

PMID- 22420583
TI  - Compliance with home non-invasive ventilation.
AB  - Home non-invasive ventilation (NIV) is being increasingly employed to treat
      chronic hypercapnic respiratory failure. However, there is little data on
      compliance with home NIV. Sixty-five patients, aged 72.6 +/- 9.4 years, who were
      using home NIV were administered a questionnaire on symptomatology and adverse
      effects associated with home NIV. Mean daily use of home NIV was 7.3 +/- 2.9
      h/day, and the median percentage of days on which home NIV was used for >=4 h/day
      was 96.7%.

PMID- 22420582
TI  - Progestogens to prevent preterm birth in twin pregnancies: an individual
      participant data meta-analysis of randomized trials.
AB  - BACKGROUND: Preterm birth is the principal factor contributing to adverse
      outcomes in multiple pregnancies. Randomized controlled trials of progestogens to
      prevent preterm birth in twin pregnancies have shown no clear benefits. However,
      individual studies have not had sufficient power to evaluate potential benefits
      in women at particular high risk of early delivery (for example, women with a
      previous preterm birth or short cervix) or to determine adverse effects for rare
      outcomes such as intrauterine death. METHODS/DESIGN: We propose an individual
      participant data meta-analysis of high quality randomized, double-blind, placebo
      controlled trials of progestogen treatment in women with a twin pregnancy. The
      primary outcome will be adverse perinatal outcome (a composite measure of
      perinatal mortality and significant neonatal morbidity). Missing data will be
      imputed within each original study, before data of the individual studies are
      pooled. The effects of 17-hydroxyprogesterone caproate or vaginal progesterone
      treatment in women with twin pregnancies will be estimated by means of a random
      effects log-binomial model. Analyses will be adjusted for variables used in
      stratified randomization as appropriate. Pre-specified subgroup analysis will be
      performed to explore the effect of progestogen treatment in high-risk groups.
      DISCUSSION: Combining individual patient data from different randomized trials
      has potential to provide valuable, clinically useful information regarding the
      benefits and potential harms of progestogens in women with twin pregnancy overall
      and in relevant subgroups.

PMID- 22420584
TI  - Replacement of fentanyl infusion by enteral methadone decreases the weaning time
      from mechanical ventilation: a randomized controlled trial.
AB  - INTRODUCTION: Patients undergoing mechanical ventilation (MV) are frequently
      administered prolonged and/or high doses of opioids which when removed can cause
      a withdrawal syndrome and difficulty in weaning from MV. We tested the hypothesis
      that the introduction of enteral methadone during weaning from sedation and
      analgesia in critically ill adult patients on MV would decrease the weaning time
      from MV. METHODS: A double-blind randomized controlled trial was conducted in the
      adult intensive care units (ICUs) of four general hospitals in Brazil. The 75
      patients, who met the criteria for weaning from MV and had been using fentanyl
      for more than five consecutive days, were randomized to the methadone (MG) or
      control group (CG). Within the first 24 hours after study enrollment, both groups
      received 80% of the original dose of fentanyl, the MG received enteral methadone
      and the CG received an enteral placebo. After the first 24 hours, the MG received
      an intravenous (IV) saline solution (placebo), while the CG received IV fentanyl.
      For both groups, the IV solution was reduced by 20% every 24 hours. The groups
      were compared by evaluating the MV weaning time and the duration of MV, as well
      as the ICU stay and the hospital stay. RESULTS: Of the 75 patients randomized,
      seven were excluded and 68 were analyzed: 37 from the MG and 31 from the CG.
      There was a higher probability of early extubation in the MG, but the difference
      was not significant (hazard ratio: 1.52 (95% confidence interval (CI) 0.87 to
      2.64; P = 0.11). The probability of successful weaning by the fifth day was
      significantly higher in the MG (hazard ratio: 2.64 (95% CI: 1.22 to 5.69; P <
      0.02). Among the 54 patients who were successfully weaned (29 from the MG and 25
      from the CG), the MV weaning time was significantly lower in the MG (hazard
      ratio: 2.06; 95% CI 1.17 to 3.63; P < 0.004). CONCLUSIONS: The introduction of
      enteral methadone during weaning from sedation and analgesia in mechanically
      ventilated patients resulted in a decrease in the weaning time from MV.

PMID- 22420586
TI  - Role of VEGF and matrix metalloproteinase-9 in peritumoral brain edema associated
      with supratentorial benign meningiomas.
AB  - Accumulating evidence indicates that VEGF and matrix metalloproteinase-9 (MMP-9)
      play a central role in the development of peritumoral brain edema (PTBE)
      associated with human brain tumors. However, the roles of these proteins,
      particularly of MMP-9, in PTBE associated with benign meningiomas have not been
      elucidated. We investigated the association between clinical features and
      biological factors, such as VEGF and MMP-9, and the incidence of PTBE and edema
      index (EI) in 60 patients with benign meningiomas. In this study, supratentorial
      lesions were examined for evaluating the extent of PTBE in the surrounding normal
      brain tissue. VEGF and MMP-9 expression was immunohistochemically examined.
      Multivariate analysis revealed that the presence of pial blood supply (odds ratio
      [OR] 12.250; P = 0.0096) and VEGF (OR 7.683; P = 0.0155), but not MMP-9 (OR
      1.178; P = 0.8113), expression are significant factors that independently predict
      the incidence of PTBE and influence EI. VEGF (P = 0.0397) and MMP-9 (P = 0.0057)
      expression correlates with the presence of pial blood supply. Moreover, tumors
      with high VEGF and MMP-9 expression had higher EIs than those with high
      expression of either (P = 0.030). Our findings suggest that MMP-9 expression was
      positively related to VEGF expression and pial blood supply and promoted the
      occurrence of PTBE by inducing the disruption of the arachnoid membrane and
      formation of pial blood supply.

PMID- 22420588
TI  - Misuse of the Mood Disorders Questionnaire as a case-finding measure and a
      critique of the concept of using a screening scale for bipolar disorder in
      psychiatric practice.
AB  - OBJECTIVES: Under-recognition of bipolar disorder (BD) is common and incurs
      significant costs for individuals and society. Clinicians are often encouraged to
      use screening instruments to help them identify patients with the disorder. The
      Mood Disorder Questionnaire (MDQ) is the most widely studied measure for this
      purpose. Some studies, however, have used the MDQ as a case-finding instrument
      rather than a screening scale. Such inappropriate use of screening scales risks
      distorting perceptions about many facets of BD, from its prevalence to its
      consequences. METHODS: Studies using the MDQ were reviewed to identify those
      reports that have used the scale as a case-finding measure rather than a
      screening scale. RESULTS: Multiple studies were identified in the BD literature
      that used the MDQ as a diagnostic proxy. The findings of these studies were
      misinterpreted because of the failure to make the distinction between screening
      and case-finding. CONCLUSIONS: Inappropriate conclusions have been drawn
      regarding the prevalence, morbidity, and diagnostic under-recognition of BD in
      studies that rely on the MDQ as a diagnostic proxy. A conceptual critique is
      offered against the use of self-administered screening questionnaires for the
      detection of BD in psychiatric settings.

PMID- 22420587
TI  - Increased differentiation capacity of bone marrow-derived mesenchymal stem cells
      in aquaporin-5 deficiency.
AB  - Mesenchymal stem cells (MSCs) are adult stem cells with a self-renewal and
      multipotent capability and express extensively in multitudinous tissues. We found
      that water channel aquaporin-5 (AQP5) is expressed in bone marrow-derived MSCs
      (BMMSCs) in the plasma membrane pattern. BMMSCs from AQP5(-/-) mice showed
      significantly lower plasma membrane water permeability than those from AQP5(+/+)
      mice. In characterizing the cultured BMMSCs from AQP5(-/-) and AQP5(+/+) mice, we
      found no obvious differences in morphology and proliferation between the 2
      genotypes. However, the multiple differentiation capacity was significantly
      higher in AQP5(-/-) than AQP5(+/+) BMMSCs as revealed by representative staining
      by Oil Red O (adipogenesis); Alizarin Red S and alkaline phosphatase (ALP;
      osteogenesis); and type II collagen and Safranin O (chondrogenesis) after
      directional induction. Relative mRNA expression levels of 3 lineage
      differentiation markers, including PPARgamma2, C/EBPalpha, adipsin, collagen 1a,
      osteopontin, ALP, collagen 11a, collagen 2a, and aggrecan, were significantly
      higher in AQP5(-/-) -differentiating BMMSCs, supporting an increased
      differentiation capacity of AQP5(-/-) BMMSCs. Furthermore, a bone-healing process
      was accelerated in AQP5(-/-) mice in a drill-hole injury model. Mechanistic
      studies indicated a significantly lower apoptosis rate in AQP5(-/-) than
      AQP5(+/+) BMMSCs. Apoptosis inhibitor Z-VAD-FMK increased the differentiation
      capacity to a greater extent in AQP5(+/+) than AQP5(-/-) BMMSCs. We conclude that
      AQP5-mediated high plasma membrane water permeability enhances the apoptosis rate
      of differentiating BMMSCs, thus decreasing their differentiation capacity. These
      data implicate AQP5 as a novel determinant of differentiation of BMMSCs and
      therefore a new molecular target for regulating differentiation of BMMSCs during
      tissue repair and regeneration.

PMID- 22420589
TI  - Grey matter differences in bipolar disorder: a meta-analysis of voxel-based
      morphometry studies.
AB  - OBJECTIVE: Several neuroimaging studies have reported structural brain
      differences in bipolar disorder using automated methods. While these studies have
      several advantages over those using region of interest techniques, no study has
      yet estimated a summary effect size or tested for between-study heterogeneity. We
      sought to address this issue using meta-analytic techniques applied for the first
      time in bipolar disorder at the level of the individual voxel. METHODS: A
      systematic review identified 16 voxel-based morphometry (VBM) studies comparing
      individuals with bipolar disorder with unaffected controls, of which eight were
      included in the meta-analysis. In order to take account of heterogeneity, summary
      effect sizes were computed using a random-effects model with appropriate
      correction for multiple testing. RESULTS: Compared with controls, subjects with
      bipolar disorder had reduced grey matter in a single cluster encompassing the
      right ventral prefrontal cortex, insula, temporal cortex, and claustrum. Study
      heterogeneity was widespread throughout the brain; though the significant cluster
      of grey matter reduction remained once these extraneous voxels had been removed.
      We found no evidence of publication bias (Eggers p = 0.63). CONCLUSIONS: Bipolar
      disorder is consistently associated with reductions in right prefrontal and
      temporal lobe grey matter. Reductions elsewhere may be obscured by clinical and
      methodological heterogeneity.

PMID- 22420590
TI  - Efficacy of electroconvulsive therapy in bipolar versus unipolar major
      depression: a meta-analysis.
AB  - OBJECTIVE: Bipolar major depression differs considerably from unipolar major
      depression with regard to the efficacy of treatment with antidepressants. In
      bipolar depression, response to treatment with antidepressants is disappointing.
      Whether response to electroconvulsive therapy (ECT) differs between bipolar and
      unipolar depression remains unclear. Therefore, this systematic review
      investigates the relative efficacy of ECT in both forms of depression. METHODS:
      Relevant cohort studies were identified from a systematic search of the PubMed
      electronic database. Six studies were included in this meta-analysis. RESULTS: In
      this meta-analysis, the overall remission rate was 50.9% (n = 402/790) for
      patients with unipolar depression and 53.2% (n = 168/316) for patients with
      bipolar major depression. A pooled odds ratio (OR) and confidence interval (CI)
      were calculated using random-effects meta-analysis with the Mantel-Haenzel
      method. This analysis shows similar efficacy of ECT in patients with unipolar and
      bipolar depression (OR = 1.08, 95% CI: 0.75-1.57). CONCLUSION: ECT appears to be
      equally effective for both bipolar and unipolar depression and the remission
      rates are encouraging, especially for bipolar depression.

PMID- 22420591
TI  - Effect of oxidative stress on TRPM2 and TRPC3 channels in B lymphoblast cells in
      bipolar disorder.
AB  - OBJECTIVES: Recent findings implicate the calcium-permeable nonselective ion
      channels transient receptor potential (TRP) melastatin subtype 2 (TRPM2) and
      canonical subtype 3 (TRPC3) in the pathogenesis of bipolar disorder (BD). These
      channels are involved in calcium and oxidative stress signaling, both of which
      are disrupted in BD. Thus, we sought to determine if these channels are
      differentially affected by oxidative stress in cell lines of BD patient origin.
      METHODS: B lymphoblast cell lines (BLCLs) from bipolar I disorder (BD-I) patients
      (n = 6) and healthy controls (n = 5) were challenged with the oxidative stressor
      rotenone (2.5 MUM and 10 MUM) or vehicle for acute (24 hours) and chronic (four
      days) intervals. Cell viability was measured using propidium iodide, while TRPM2-
      and TRPC3-mediated calcium fluxes were measured in the presence of their
      respective activators (H(2) O(2) and 1-oleoyl-2-acetyl-sn-glycerol) using Fluo-4.
      Changes in TRPM2 and TRPC3 expression levels were determined by quantitative
      reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting.
      RESULTS: Cell viability decreased with increasing dose and duration of rotenone
      treatment, with BD-I patient BLCLs more susceptible than controls acutely (p <
      0.001). A dose-dependent decrease in TRPC3 protein expression occurred after
      chronic (24%, p = 0.008) but not acute rotenone treatment. Interestingly, H(2)
      O(2) -provoked TRPM2-dependent calcium fluxes revealed an interaction between the
      effects of stressor addition and diagnostic subject group (p = 0.003).
      CONCLUSIONS: These data support an important role for TRPM2 and TRPC3 in sensing
      and responding to oxidative stress and in transducing oxidative stress signaling
      to intracellular calcium homeostasis and cellular stress responses, all of which
      have been implicated in the pathophysiology of BD.

PMID- 22420592
TI  - Amygdala activity and prefrontal cortex-amygdala effective connectivity to
      emerging emotional faces distinguish remitted and depressed mood states in
      bipolar disorder.
AB  - OBJECTIVES: Few studies have employed effective connectivity (EC) to examine the
      functional integrity of neural circuitry supporting abnormal emotion processing
      in bipolar disorder (BD), a key feature of the illness. We used Granger Causality
      Mapping (GCM) to map EC between the prefrontal cortex (PFC) and bilateral
      amygdala and a novel paradigm to assess emotion processing in adults with BD.
      METHODS: Thirty-one remitted adults with BD [(remitted BD), mean age = 32 years],
      21 adults with BD in a depressed episode [(depressed BD), mean age = 33 years],
      and 25 healthy control participants [(HC), mean age = 31 years] performed a block
      design emotion processing task requiring color-labeling of a color flash
      superimposed on a task-irrelevant face morphing from neutral to emotional (happy,
      sad, angry, or fearful). GCM measured EC preceding (top-down) and following
      (bottom-up) activity between the PFC and the left and right amygdalae. RESULTS:
      Our findings indicated patterns of abnormally elevated bilateral amygdala
      activity in response to emerging fearful, sad, and angry facial expressions in
      remitted-BD subjects versus HC, and abnormally elevated right amygdala activity
      to emerging fearful faces in depressed-BD subjects versus HC. We also showed
      distinguishable patterns of abnormal EC between the amygdala and dorsomedial and
      ventrolateral PFC, especially to emerging happy and sad facial expressions in
      remitted-BD and depressed-BD subjects. DISCUSSION: EC measures of neural system
      level functioning can further understanding of neural mechanisms associated with
      abnormal emotion processing and regulation in BD. Our findings suggest major
      differences in recruitment of amygdala-PFC circuitry, supporting implicit emotion
      processing between remitted-BD and depressed-BD subjects, which may underlie
      changes from remission to depression in BD.

PMID- 22420593
TI  - A longitudinal functional connectivity analysis of the amygdala in bipolar I
      disorder across mood states.
AB  - OBJECTIVE: Bipolar I disorder is characterized by affective symptoms varying
      between depression and mania. The specific neurophysiology responsible for
      depression in bipolar I disorder is unknown but previous neuroimaging studies
      suggest impairments in corticolimbic regions that are responsible for regulating
      emotion. The amygdala seems to play a central role in this network and is
      responsible for appraisal of emotional stimuli. To further understand the role of
      the amygdala in the generation of mood symptoms, we used functional magnetic
      resonance imaging (fMRI) to examine a group of patients with bipolar I disorder
      longitudinally. METHODS: fMRI was used to study regional brain activation in 15
      bipolar I disorder patients followed for up to one year. Patients received an
      fMRI scan during an initial manic episode and a subsequent depressive episode.
      During the scans, patients performed an attentional task that incorporated
      emotional pictures. Fifteen healthy comparison subjects were also scanned at
      baseline and then at four months. Whole-brain functional connectivity analysis
      was performed using the left and right amygdala as seed regions. RESULTS:
      Significant changes in amygdala functional connectivity were found between the
      manic and depressed phases of illness. The right amygdala was significantly more
      positively correlated with the left inferior frontal gyrus during mania and with
      the right insula during depression. There were no significant differences in left
      amygdala correlations across mood states in the bipolar I disorder group.
      CONCLUSIONS: In the transition from a manic/mixed episode to a depressive
      episode, subjects with bipolar I disorder showed unique changes in cortical
      amygdala functional connectivity. Increased connectivity between the insula and
      right amygdala may generate excessive positive feedback, in that both of these
      regions are involved in the appraisal of emotional stimuli. Increased correlation
      between the right amygdala and the inferior frontal gyrus in mania is consistent
      with previous findings of decreased prefrontal modulation of limbic regions in
      mania. These differences in connectivity may represent neurofunctional markers of
      mood state as they occurred in the same individuals across manic and depressive
      episodes.

PMID- 22420594
TI  - Facilitated Integrated Mood Management for adults with bipolar disorder.
AB  - OBJECTIVES: We describe the development of a five-session psychoeducational
      treatment, Facilitated Integrated Mood Management (FIMM), which contains many of
      the core elements of longer evidence-based psychosocial treatments for bipolar
      disorder. FIMM incorporated a novel mood monitoring program based on mobile phone
      technology. METHODS: Adult patients with bipolar I and II disorders (N = 19)
      received six sessions (Pilot I: n = 14) or five sessions (Pilot II: n = 5) of
      FIMM with pharmacotherapy. Treatment facilitators were novice counselors who were
      trained in a three-day workshop and supervised for six months. FIMM sessions
      focused on identifying early signs of recurrence, maintaining regular daily and
      nightly routines, rehearsing mood management strategies, maintaining adherence to
      medications, and education about substance abuse. Patients sent daily text
      messages or e-mails containing ratings of their mood and sleep, and weekly
      messages containing self-ratings on the Quick Inventory of Depressive
      Symptomatology (QIDS) and the Altman Self Rating Mania Scale (ASRM). Patients
      also completed a weekly mood management strategies questionnaire. RESULTS: Of the
      19 patients, 17 (89.5%) completed FIMM in an average of 9.2 +/- 3.4 weeks (Pilot
      I) and 7.6 +/- 0.9 weeks (Pilot II). Patients reported stable moods on the QIDS
      and ASRM over a 120-day period, and on average responded to 81% of the daily
      message prompts and 88% of the weekly QIDS and ASRM prompts. Facilitators
      maintained high levels of fidelity to the FIMM manual. Patients' knowledge of
      mood management strategies increased significantly between the first and last
      weeks of treatment. CONCLUSIONS: Patients with bipolar disorder can be engaged in
      a short program of facilitated mood management. The effects of FIMM on the course
      of bipolar disorder await evaluation in randomized trials. The program may be a
      useful adjunct to pharmacotherapy in community centers that cannot routinely
      administer full courses of psychosocial treatment.

PMID- 22420595
TI  - Cognition in older adults with bipolar disorder versus major depressive disorder.
AB  - OBJECTIVES: Bipolar disorder (BD) and major depressive disorder (MDD) are
      associated with cognitive dysfunction in older age during both acute mood
      episodes and remitted states. The purpose of this study was to investigate for
      the first time the similarities and differences in the cognitive function of
      older adults with BD and MDD that may shed light on mechanisms of cognitive
      decline. METHODS: A total of 165 subjects with BD (n = 43) or MDD (n = 122), ages
      >= 65 years [mean (SD) 74.2 (6.2)], were assessed when euthymic, using
      comprehensive measures of cognitive function and cognitive-instrumental
      activities of daily living (C-IADLs). Test results were standardized using a
      group of mentally healthy individuals (n = 92) of comparable age and education
      level. RESULTS: Subjects with BD and MDD were impaired across all cognitive
      domains compared with controls, most prominently in Information Processing
      Speed/Executive Function. Despite the protective effects of having higher
      education and lower vascular burden, BD subjects were more impaired across all
      cognitive domains compared with MDD subjects. Subjects with BD and MDD did not
      differ significantly in C-IADLs. CONCLUSION: In older age, patients with BD have
      worse overall cognitive function than patients with MDD. Our findings suggest
      that factors intrinsic to BD appear to be related to cognitive deterioration and
      support the understanding that BD is associated with cognitive decline.

PMID- 22420596
TI  - Allopurinol augmentation in the outpatient treatment of bipolar mania: a pilot
      study.
AB  - BACKGROUND: Allopurinol promotes the salvage of purines, possibly increasing
      endogenous adenosine levels. Recent studies suggest that adenosine has
      neuroprotective and inhibitory effects. Two previous inpatient trials
      demonstrated that allopurinol has anti-manic activity. Our objective was to test
      allopurinol as an adjunct to standard medications in bipolar disorder manic
      outpatients. METHODS: In this double-blind, placebo-controlled trial, 27 subjects
      who met DSM-IV criteria for bipolar disorder and scored >= 14 on the Young Mania
      Rating Scale (YMRS) were randomized to augmentation with allopurinol or placebo
      for six weeks. The primary efficacy measure was the YMRS. The primary safety
      measure was the Treatment Emergent Symptom Scale. RESULTS: The effect of
      allopurinol augmentation in decreasing mean YMRS scores was modest, with an
      overall effect size of -0.25 (Cohen's d). Allopurinol-treated individuals who
      abstained from caffeine (n = 4) had a greater decrease in YMRS scores (-15.3 +/-
      1.8) than subjects using caffeine (n = 5) (-9.6 +/- 3.4, p = 0.219), with an
      effect size of -0.86. CONCLUSION: In this small outpatient pilot study,
      allopurinol augmentation did not show a statistically significant improvement
      over placebo in attenuating manic symptoms. Subjects with restricted caffeine use
      showed a greater effect size compared to caffeine users. This finding may be
      interpreted as corroborating the hypothesized mechanism of action of
      allopurinol's anti-manic effect in previous studies.

PMID- 22420597
TI  - A randomized pilot study of psychotherapy and quetiapine for the acute treatment
      of bipolar II depression.
AB  - OBJECTIVES: The differential roles of psychotherapy and pharmacotherapy in the
      management of bipolar (BP) II depression are unknown. As a first step toward
      exploring this issue, we conducted a pilot study to evaluate the feasibility and
      acceptability of comparing a BP-specific psychotherapy [Interpersonal and Social
      Rhythm Therapy (IPSRT)] to quetiapine as treatments for BP-II depression.
      METHODS: Unmedicated individuals (n = 25) meeting DSM-IV criteria for BP-II
      disorder, currently depressed, were randomly assigned to weekly sessions of IPSRT
      (n = 14) or quetiapine (n = 11), flexibly dosed from 25-300 mg. Participants were
      assessed with weekly measures of mood and followed for 12 weeks. Treatment
      preference was queried prior to randomization. RESULTS: Using mixed effects
      models, both groups showed significant declines in the 25-item Hamilton Rating
      Scale for Depression [F(1,21) = 44, p < 0.0001] and Young Mania Rating Scale
      [F(1,21) = 20, p = 0.0002] scores over time but no group-by-time interactions.
      Dropout rates were 21% (n = 3) and 27% (n = 3) in the IPSRT and quetiapine
      groups, respectively. Overall response rates (defined as >= 50% reduction in
      depression scores without an increase in mania scores) were 29% (n = 4) in the
      IPSRT group and 27% (n = 3) in the quetiapine group. Measures of treatment
      satisfaction were high in both groups. Treatment preference was not associated
      with outcomes. CONCLUSIONS: Outcomes in participants with BP-II depression
      assigned to IPSRT monotherapy or quetiapine did not differ over 12 weeks in this
      small study. Follow-up trials should examine characteristics that predict
      differential response to psychotherapy and pharmacotherapy.

PMID- 22420598
TI  - Hf(IV)-catalyzed enantioselective epoxidation of N-alkenyl sulfonamides and N
      tosyl imines.
AB  - Asymmetric epoxidation of allylic and homoallylic amine derivatives catalyzed by
      Hf(IV)-bishydroxamic acid complexes is described. Under similar conditions,
      aldimine and ketimine produced oxaziridines. The sulfonyl group is demonstrated
      to be an effective directing group for these transformations.

PMID- 22420599
TI  - Reticulated pigmentary changes in a patient with a variant form of Lesch-Nyhan
      disease.

PMID- 22420600
TI  - Characterization of sulfated quercetin and epicatechin metabolites.
AB  - Different monosulfates of quercetin and epicatechin with metabolic interest were
      obtained by hemisynthesis and characterized regarding their chromatographic
      behavior and absorption and mass spectra. Three of these compounds were further
      isolated, and their structures were elucidated by mass spectrometry and (1)H and
      (13)C nuclear magnetic resonance using one- and two-dimensional techniques
      (heteronuclear single-quantum coherence and heteronuclear multiple-bond
      correlation). The calculation of the proton and carbon shifts caused by sulfation
      allowed for the assignment of the position of the sulfate group in the
      flavonoids, so that the compounds were identified as quercetin-3'-O-sulfate,
      quercetin 4'-O-sulfate, and epicatechin 4'-O-sulfate. It was found that sulfation
      at position 3' induced a large upfield shift in the carbon bearing the sulfate
      group and downfield displacements of the adjacent carbons, whereas no significant
      upfield or downfield shifts were observed with respect to the parent flavonoid
      when sulfation was produced at position 4'.

PMID- 22420601
TI  - Dual-opioid therapy: changing the paradigm. Introduction.
AB  - INTRODUCTION: Morphine sulfate and oxycodone hydrochloride are commonly used for
      pain management because of their pharmacologic profile, pharmacokinetics, and
      analgesic potency. However, opioids are associated with a significant adverse
      event (AE) burden that limits their use in both the acute and the chronic pain
      settings. SUMMARY: Co-administration of opioids demonstrated synergistic
      analgesia and reduced side effects. Thus, dual-opioid therapy has the potential
      to enhance the positive analgesic benefits of opioids, while limiting the burden
      of opioid-related AEs. This symposium proceedings was based on presentations at
      the 13th World Congress on Pain in August 2010. CONCLUSIONS: This program will
      review the rationale for dual-opioid therapy based on preclinical findings and
      data from clinical studies showing the efficacy and tolerability profile of a
      dual-opioid formulation when used to treat acute postoperative pain.

PMID- 22420602
TI  - Efficacy and safety of dual-opioid therapy in acute pain.
AB  - BACKGROUND: Although opioids are widely accepted as standard therapy for treating
      acute postoperative pain, the frequent occurrence of adverse events (AEs) and the
      substantial burden on the patient and the costs of care are a barrier to optimal
      dosing and adherence to prescribed treatment. Coadministration of two opioids is
      not often recommended as a multimodal treatment option for moderate to severe
      acute pain because of lack of knowledge about the potential benefit of such
      combinations and due to potential concerns about side effects and doubts about
      the added benefits. Study results on the coadministration of two or more opioids
      demonstrate synergistic analgesia with a similar or lower incidence of opioid
      related AEs. One such combination is morphine and oxycodone. SUMMARY: Moxduo(r)
      (morphine/oxycodone 3/2) is a dual-opioid combination of morphine and oxycodone
      used to treat acute pain. Independent controlled studies of the coadministration
      of morphine plus oxycodone demonstrate excellent analgesia with a lower incidence
      or less-intense AEs, especially nausea and vomiting, compared with equianalgesic
      doses of individual opioids. Controlled trials with morphine/oxycodone 3/2 have
      enrolled approximately 1,500 subjects with moderate to severe post-surgical pain
      who received multiple doses of morphine/oxycodone 3/2 or single-entity opioids
      for a maximum of 23 days. These phase 2 and phase 3 clinical studies demonstrate
      analgesic efficacy that is at least comparable to the individual components and
      showing a 50-75% reduction in moderate to severe AEs, especially nausea and
      vomiting. CONCLUSION: Thus, the dual-opioid combination product,
      morphine/oxycodone 3/2, compared with equianalgesic monotherapy doses of
      oxycodone or morphine may provide effective relief of moderate or severe post
      surgical pain, while reducing the impact of AEs on patients and prescribers.

PMID- 22420603
TI  - Dual-opioid therapy: changing the paradigm. Panel discussion.

PMID- 22420604
TI  - Preclinical pharmacology and opioid combinations.
AB  - Although effective alone, opioids are often used in combination with other drugs
      for relief of moderate to severe pain. Guidelines for acute perioperative pain
      recommend the use of multimodal therapy for pain management, although
      combinations of opioids are not specifically recommended. Mu opioid drugs include
      morphine, heroin, fentanyl, methadone, and morphine 6beta-glucuronide (M6G).
      Their mechanism of action is complex, resulting in subtle pharmacological
      differences among them and with unpredictable differences in their potency,
      effectiveness, and tolerability among patients. Highly selective mu opioids do
      not bind to a single receptor. Rather, they interact with a large number of mu
      receptor subtypes with different activation profiles for the various drugs. Thus,
      mu-receptor-based drugs are not all the same and it may be possible to utilize
      these differences for enhanced pain control in a clinical setting. These
      differences among the drugs raise the question of whether combinations might
      result in better pain relief with fewer side effects. This concept has already
      been demonstrated between two mu opioids in preclinical studies and clinical
      trials on other combinations are ongoing. This article reviews the current state
      of knowledge about mu opioid receptor pharmacology, summarizes preclinical
      evidence for synergy from opioid combinations, and highlights the complex nature
      of the mu opioid receptor pharmacology.

PMID- 22420605
TI  - Three-dimensional digital models for rating dental arch relationships in
      unilateral cleft lip and palate.
AB  - Objective : To determine the reliability and reproducibility of using three
      dimensional digital models as an alternative to plaster models for rating dental
      arch relationships in patients born with unilateral cleft lip and palate. Design
      : Reliability and reproducibility study. Methods : Study models of 45 patients
      born with unilateral cleft lip and palate were made available in plaster and
      three-dimensional digital models. Records were scored a week apart by three
      examiners using the 5-year-olds' index reference models in the same two formats
      as the patient models. To assess reproducibility the study was repeated 4 weeks
      later under similar conditions to minimize the influence of memory bias on the
      results. The reliability of using the three-dimensional digital models was
      determined by comparing the scores for each examiner with the plaster model
      scores. Results : Weighted kappa statistics indicated repeatability for the
      plaster models was very good (.83 to .87). For the three-dimensional digital
      models it was good to very good (.74 to .83). Overall, the use of the three
      dimensional digital models showed good agreement with the plaster model scores on
      both occasions. Conclusion : Three-dimensional digital models appear to be a good
      alternative to plaster models for assessing dental arch relationships using the 5
      year-olds' index.

PMID- 22420606
TI  - Cu(ClO(4))(2)-mediated arene C-H bond halogenations of azacalixaromatics using
      alkali metal halides as halogen sources.
AB  - Regiospecific halogenation of azacalix[1]arene[3]pyridines at the lower rim
      position of the benzene ring was achieved from their cross-coupling reaction with
      cost-effective alkali metal halides through the Cu(ClO(4))(2)-mediated aerobic
      aryl C-H activation, which gave structurally well-defined aryl-Cu(III)
      intermediates, and a subsequent C-X bond formation reaction under very mild
      conditions.

PMID- 22420607
TI  - Hormone concentrations in the homogenates of ovarian tissue and blood serum in
      postmenopausal women not using hormone therapy.
AB  - Ovaries in postmenopausal women synthesize steroids, mostly androgens. Removal of
      the ovaries after menopause may be reflected by menopausal symptoms and arterial
      hypertension observed during postoperative period, along with a significantly
      increased risk of death due to cardiovascular complications. It is not understood
      if the clinical consequences of gonad removal at different time points after
      menopause are similar. The aim of this study was to evaluate ovarian
      steroidogenesis and consequently to define the role of the ovaries in
      postmenopausal women depending on the time after menopause. Concentrations of
      hormones were determined in ovarian homogenates and serum of postmenopausal
      women. This study included 207 postmenopausal women. They were divided into
      groups depending on the time after menopause. All participants had laparotomic
      removal of the ovaries. Concentrations of estradiol, testosterone and
      androstenedione were measured in ovarian homogenate and serum. The study revealed
      that ovarian homogenate and serum concentrations of estradiol, testosterone and
      androstenedione were the highest in women up to 5 years after menopause and since
      then significantly decreased. This study showed that testosterone,
      androstenedione and estradiol are synthesized in the postmenopausal ovaries. The
      peak synthesis of these hormones occurs up to 5 years after menopause and
      significantly decreases thereafter.

PMID- 22420608
TI  - Quantitative analysis of waterfowl parvoviruses in geese and Muscovy ducks by
      real-time polymerase chain reaction: correlation between age, clinical symptoms
      and DNA copy number of waterfowl parvoviruses.
AB  - BACKGROUND: Waterfowl parvoviruses cause serious loss in geese and ducks
      production. Goose parvovirus (GPV) is infectious for geese and ducks while
      Muscovy duck parvovirus (MDPV) infects Muscovy ducks only. So far, for these
      viruses' sensitive detection polymerase chain reaction (PCR) and loop-mediated
      isothermal amplification (LAMP) were applied. However, there was no molecular
      biology method for both waterfowl parvoviruses detection and quantification which
      could unify the laboratory procedures. The level of GPV and MDPV replication and
      distribution plays a significant role in the parvoviral infection progress and is
      strictly correlated to clinical symptoms. Meanwhile, experiments conducted
      previously on GPV distribution in geese, performed as animal trial, did not
      involve epidemiological data from the disease field cases. The study on the
      correlation between age, clinical symptoms and viral DNA copy number may be
      benefitable in understanding the GPV and MDPV infection. Such data may also aid
      in determination of the stage and severity of the infection with parvoviruses.
      Therefore the aim of this study was to develop quantitative real-time PCR for
      parallel detection of GPV and MDPV in geese and Muscovy ducks and to determine
      the correlation between the age of the infected birds, clinical symptoms and DNA
      copy number for the estimation of the disease stage or severity. RESULTS: In
      order to develop quantitative real-time PCR the viral material was collected from
      13 farms of geese and 3 farms of Muscovy ducks. The designed primers and Taqman
      probe for real-time PCR were complementary to GPV and MDPV inverted terminal
      repeats region. The pITR plasmid was constructed, purified and used to prepare
      dilutions for standard curve preparation and DNA quantification. The applied
      method detected both GPV and MDPV in all the examined samples extracted from the
      heart and liver of the infected birds. The conducted correlation tests have shown
      relationship between age, clinical symptoms during parvoviral infection and the
      DNA copy number of these pathogens. The method allowed for a sensitive detection
      of GPV and MDPV even in 1-week old infected goslings or 2-week old ducklings
      before observation of any disease symptoms. CONCLUSIONS: The developed method was
      found to be a valuable tool for the unification of laboratory procedures and both
      parvoviruses parallel detection and quantification. The conducted analysis
      revealed significant correlation between the age of the infected birds, the
      observed clinical symptoms and DNA copy number of GPV and MDPV in the examined
      organs. The obtained data may aid in better understanding of the pathogenesis and
      epidemiology of Derzsy's disease and 3-w disease as well as estimation of the
      infection's severity and stage of the disease.

PMID- 22420610
TI  - Cryopreservation of human testicular diploid germ cell suspensions.
AB  - For patients with threatened fertility, preservation of it is a major concern.
      Although promising results have been obtained in animal models using testicular
      germ cell suspensions, in humans, it is crucial to first develop an efficient
      method of cryopreservation to be able to apply to transplantation. Thus, four
      reliable and available cryopreservation techniques in any fertility centre were
      tested to cryopreserve an enriched fraction of diploid germ cells isolated from
      human testicular biopsies. The protocols were evaluated based on cell viability,
      and the results showed significant differences between the four methods. The
      semen and tissue cryopreservation methods appeared to be inadequate for diploid
      germ cell suspensions, and programmed slow freezing gave significantly lower
      results than open pulled straw vitrification; the latter was found to be the
      protocol that best preserved cell viability. The vitrification of isolated human
      diploid germ cells is innovative and constitutes valuable information for
      cryopreservation in cases of transplants or in vitro maturation.

PMID- 22420611
TI  - Beneficial effects of rosuvastatin on insulin resistance, adiposity, inflammatory
      markers and non-alcoholic fatty liver disease in mice fed on a high-fat diet.
AB  - The aim of the present study was to evaluate the effects of ST (rosuvastatin) and
      GZ (rosiglitazone) on IR (insulin resistance) and on liver as well as adipose
      tissue in mice fed on an HF (high-fat) diet. Our data show that treatment with ST
      resulted in a marked improvement in insulin sensitivity characterized by enhanced
      glucose clearance during the insulin tolerance test and a 70% decrease in the
      HOMA-IR (homoeostasis model assessment of insulin resistance) index level
      (P=0.0008). The ST-treated mice exhibited lower gains in BM (body mass; -8%;
      P<0.01) and visceral fat pad thickness (-60%; P<0.01) compared with the untreated
      HF group. In comparison with HF-diet-fed mice, HF+ST-treated mice showed a
      significant reduction in hepatomegaly and liver steatosis (-6%, P<0.05; and -21%,
      P<0.01 respectively). In HF+ST-treated mice, the hepatic TAG (triacylglycerol)
      levels were reduced by 58% compared with the HF group (P<0.01). In addition, the
      expression of SREBP-1c (sterol-regulatory-element-binding protein-1c) was
      decreased by 50% in the livers of HF+ST-treated mice (P<0.01) relative to the HF
      diet-fed mice. The levels of resistin were lower in the HF+ST-treated group
      compared with the HF group (44% less, P< 0.01). In conclusion, we demonstrated
      that ST treatment improved insulin sensitivity and decreased liver steatosis in
      mice fed on an HF diet. Furthermore, ST reduced BM gains, improved the
      circulating levels of plasma cholesterol and TAG, and reduced hepatic TAG, which
      was concomitant with lower resistin levels.

PMID- 22420612
TI  - Modeling trade-off between PAH toxicity reduction and negative effects of sorbent
      amendments to contaminated sediments.
AB  - Adding activated carbon (AC) to contaminated sediment has been suggested as an
      effective method for sediment remediation. AC binds chemicals such as polycyclic
      aromatic hydrocarbons (PAHs), thus reducing the toxicity of the sediment.
      Negative effects of AC on benthic organisms have also been reported. Here, we
      present a conceptual model to quantify the trade-off, in terms of biomass
      changes, between the advantageous PAH toxicity reduction and the negative effects
      of AC on populations of benthic species. The model describes population growth,
      incorporates concentration-effect relationships for PAHs in the pore water and
      for AC, and uses an equilibrium sorption model to estimate PAH pore water
      concentrations as a function of AC dosage. We calibrated the model using bioassay
      data and analyzed it by calculating isoclines of zero population growth for two
      species. For the sediment evaluated here, the results show that AC may safely
      protect the benthic habitat against considerable sediment PAH concentrations as
      long as the AC dosage remains below 4%.

PMID- 22420613
TI  - Significance of PC cell-derived growth factor and cyclin D1 expression in
      cutaneous squamous cell carcinoma.
AB  - BACKGROUND: PC cell-derived growth factor (PCDGF) is an autocrine growth factor
      originally purified from the highly tumorigenic teratoma PC cell line. It
      participates in tumorigenesis and tumour progression through upregulation of
      cyclin D1. To date, there has been no report on the role of PCDGF in skin cancer,
      to our knowledge. AIM: To investigate the expression of PCDGF and cyclin D1 in
      basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and seborrhoeic
      keratosis (SK), and their relationship with the clinicopathological parameters of
      SCC. METHODS: Immunohistochemical expression of PCDGF and cyclin D1 was examined
      in 42 SCC, 30 BCC and 20 SK tissues. RESULTS: PCDGF and cyclin D1 were
      overexpressed in SCC or BCC tissues compared with normal skin or SK, and their
      expressions were significantly higher in SCC than in BCC. Moreover, positive
      expression of PCDGF and cyclin D1 was significantly correlated with depth of
      invasion and metastasis of SCC. There was significant correlation between PCDGF
      and cyclin D1 expression in SCC. CONCLUSIONS: Expression of PCDGF and cyclin D1
      plays an important role in the tumorigenesis of BCC and SCC. Abnormal expression
      of PCDGF and Cyclin D1 may be related to invasion and metastasis of SCC.

PMID- 22420614
TI  - 5-HTTLPR S-allele: a genetic plasticity factor regarding the effects of life
      events on personality?
AB  - The S-allele of the 5-HTTLPR has been identified as a genetic vulnerability
      factor, being associated with an increased risk for affective disorders and/or
      maladaptive traits (e.g. neuroticism), especially after exposition to negative
      life-events (LEs). Alternatively, it has been hypothesized that this genetic risk
      factor might constitute a genetic plasticity factor. That is, S-allele carriers
      are not only vulnerable to the negative effects of a preponderance of stressful
      LEs but also disproportionally benefit from a preponderance of positive
      environmental influences. We tested this hypothesis in 357 subjects who were
      genotyped for the 5-HTTLPR and provided self-reports of neuroticism, life
      satisfaction and LEs. Results showed a relatively increased number of positive
      LEss to be associated with reduced neuroticism (men: beta = -0.501, P < 0.05,
      women: beta = -0.369, P < 0.005) and increased life satisfaction (beta = 0.494, P
      < 0.001) within SS-homozygotes. Within SL-heterozygotes, similar tendencies were
      found. No associations were detected in LL-homozygotes. Extreme Group comparisons
      revealed a genotype * LE interaction (F(2,198)  = 5.593, P < 0.005), with SS
      homozygotes having experienced predominantly positive LEs exhibiting reduced
      neuroticism (women: F(1,34)  = 4.764, P < 0.05; men: F(1,17)  = 2.092, P = 0.17),
      and increased life satisfaction (F(1,53)  = 4.057, P < 0.05), as compared to LL
      homozygotes having experienced predominantly positive LEs. Our data support the
      idea that the S-allele of the 5-HTTLPR is associated with an overall increased
      reactivity to environmental influences, be they positive or negative in nature.
      These findings constitute a promising add-on to earlier data and support the
      plasticity hypothesis.

PMID- 22420616
TI  - The implementation of neonatal peritoneal dialysis in a clinical setting.
AB  - OBJECTIVE: To investigate etiology, outcome and complications related to neonatal
      peritoneal dialysis (PD). METHODS: Neonates treated with PD in our neonatal
      intensive care unit during 2007-2010 were analyzed retrospectively. RESULTS:
      Among 4036 hospitalized neonates; 20 neonates (0.5%) who underwent 21 cycles of
      PD [7 preterm, 13 term; 13 female, 7 male] were included. The mean birth weight
      was 2930.2 +/- 720.6 g (1120-4570), mean gestational age was 37.5 +/- 3.5 weeks
      (27-41). The etiologic disorders included inborn errors of metabolism (propionic
      acidemia, methylmalonic acidemia, citrullinemia, glutaric aciduria type 2, maple
      syrup urine disease, 10), or acute renal failure secondary to perinatal asphyxia
      (4), sepsis (2), prematurity (2), hypoplastic left heart syndrome (1),
      kernicterus (1). The complications included peritonitis (2), early leakage (4),
      hemorrhage (1), catheter removal (3) and occlusion (2). The mortality rate was
      50%. The gestational ages and birth weights of surviving neonates were higher (p
      < 0.05). Among surviving neonates, chronic renal failure (1), severe (4) and
      moderate neuromotor impairment (2) developed within 4-43 months. CONCLUSION: PD,
      although invasive, is an effective therapy in neonates. The complexity and
      invasiveness of the procedure is probably responsible for high rate of
      complications and mortality. If appropriate catheter selection and technique in
      the placement should be done, PD might improve outcome.

PMID- 22420618
TI  - Quality of life after surgery for Graves' disease: comparison of those having
      surgery intended to preserve thyroid function with those having ablative surgery.
AB  - BACKGROUND: Postoperative quality of life (QoL) after surgery for Graves' disease
      is not well documented, and the effect of different surgical operations has not
      been compared. This study examines the impact on QoL of a shift in policy from
      operations intended to preserve thyroid function (PF) to those ablating thyroid
      function (AF). METHODS: A cross-sectional assessment was performed on patients
      who underwent surgery for Graves' disease between 1986 and 2008 in a tertiary
      endocrine surgical unit. Patients completed the Short Form 36 (SF-36)
      questionnaire by post. SF-36 scores, including the physical and mental component
      summaries, were compared with the general population and by operative intent (AF
      vs. PF). Statistical analyses were performed using SPSS 16.0. RESULTS: Of 150
      patients, 3 had died of unrelated causes and 14 were not contactable. In the
      remaining 133 patients, the median age at time of assessment was 46 years
      (interquartile range 42-50) and 43 years (interquartile range 33-47) in the PF
      and AF groups, respectively. From these patients, 87 questionnaires (65.4%
      response rate) were completed with an item completion rate of 99.3%. The median
      follow-up was 18.4 years for PF and 7.9 years for AF surgery. Of 87 respondents,
      38 (43.7%) underwent PF and 49 (56.3%) AF surgery. Study participants reported
      lower scores across all SF-36 subscales than British norms (p<0.05). Comparisons
      on operative intent showed no significant difference in long-term QoL (p>0.05).
      CONCLUSION: The shift to ablative surgery simplifies postoperative management
      with no adverse effect on QoL, justifying this practice from a patient
      perspective.

PMID- 22420615
TI  - Quality of caesarean delivery services and documentation in first-line referral
      facilities in Afghanistan: a chart review.
AB  - BACKGROUND: Increasing appropriate use and documentation of caesarean section
      (CS) has the potential to decrease maternal and perinatal mortality in settings
      with low CS rates. We analyzed data collected as part of a comprehensive needs
      assessment of emergency obstetric and newborn care (EmONC) facilities in
      Afghanistan to gain a greater understanding of the clinical indications,
      timeliness, and outcomes of CS deliveries. METHODS: Records were reviewed at 78
      government health facilities expected to function as EmONC providers that were
      located in secure areas of the country. Information was collected on the three
      most recent CS deliveries in the preceding 12 months at facilities with at least
      one CS delivery in the preceding three months. After excluding 16 facilities with
      no recent CS deliveries, the sample includes 173 CS deliveries at 62 facilities.
      RESULTS: No CS deliveries were performed in the previous three months at 21% of
      facilities surveyed; all of these were lower-level facilities. Most CS deliveries
      (88%) were classified as emergencies, and only 12% were referrals from another
      facility. General anesthesia was used in 62% of cases, and spinal or epidural
      anesthesia in 34%. Only 28% of cases were managed with a partograph. Surgery
      began less than one hour after the decision for a CS delivery in just 30% of
      emergency cases. Among the 173 cases, 27 maternal deaths, 28 stillbirths, and 3
      early neonatal deaths were documented. In cases of maternal and fetal death, the
      most common indications for CS delivery were placenta praevia or abruption and
      malpresentation. In 62% of maternal deaths, the fetus was stillborn or died
      shortly after birth. In 48% of stillbirths, the fetus had a normal heart rate at
      the last check. Information on partograph use was missing in 38% of cases,
      information on parity missing in 23% of cases and indications for cesareans
      missing in 9%. CONCLUSIONS: Timely referral within and to EmONC facilities would
      decrease the proportion of CS deliveries that develop to emergency status. While
      the substantial mortality associated with CS in Afghanistan may be partly due to
      women coming late for obstetric care, efforts to increase the availability and
      utilization of CS must also focus on improving the quality of care to reduce
      mortality. Key goals should be encouraging use of partographs and improving
      decision-making and documentation around CS deliveries.

PMID- 22420619
TI  - Vitreous hemorrhage in a premature infant with patent hyaloid artery and
      increased intracranial pressure.
AB  - Reports of intraocular bleeding in infants from nonabusive causes are rare. The
      authors report a case of visually significant vitreous hemorrhage in an infant
      with a persistent hyaloid artery who also had raised intracranial pressure
      secondary to an intraventricular bleed.

PMID- 22420620
TI  - Combined hamartoma of the retina and retinal pigment epithelium in a child with
      branchial cleft cysts.
AB  - An otherwise healthy 15-month-old boy presented with benign branchial cleft cysts
      and combined hamartoma of the retina and retinal pigment epithelium. This
      association was previously only reported in a patient with branchio-oculo-facial
      syndrome. Although uncommon, this could represent multifocal sites of fetus
      craniofacial malformation.

PMID- 22420622
TI  - Reversible and irreversible higher-order cycloaddition reactions of polyolefins
      with a multiple-bonded heavier group 13 alkene analogue: contrasting the behavior
      of systems with pi-pi, pi-pi*, and pi-n+ frontier molecular orbital symmetry.
AB  - The heavier group 13 element alkene analogue, digallene Ar(iPr(4))GaGaAr(iPr(4))
      (1) [Ar(iPr(4)) = C(6)H(3)-2,6-(C(6)H(3)-2,6-(i)Pr(2))(2)], has been shown to
      react readily in [n + 2] (n = 6, 4, 2 + 2) cycloaddition reactions with
      norbornadiene and quadricyclane, 1,3,5,7-cyclooctatetraene, 1,3-cyclopentadiene,
      and 1,3,5-cycloheptatriene to afford the heavier element deltacyclane species
      Ar(iPr(4))Ga(C(7)H(8))GaAr(iPr(4)) (2), pseudoinverse sandwiches
      Ar(iPr(4))Ga(C(8)H(8))GaAr(iPr(4)) (3, 3(iso)), and polycyclic compounds
      Ar(iPr(4))Ga(C(5)H(6))GaAr(iPr(4)) (4) and Ar(iPr(4))Ga(C(7)H(8))GaAr(iPr(4)) (5,
      5(iso)), respectively, under ambient conditions. These reactions are facile and
      may be contrasted with other all-carbon versions, which require transition-metal
      catalysis or forcing conditions (temperature, pressure), or with the reactions of
      the corresponding heavier group 14 species Ar(iPr(4))EEAr(iPr(4)) (E = Ge, Sn),
      which give very different product structures. We discuss several mechanistic
      possibilities, including radical- and non-radical-mediated cyclization pathways.
      These mechanisms are consistent with the improved energetic accessibility of the
      LUMO of the heavier group 13 element multiple bond in comparison with that of a
      simple alkene or alkyne. We show that the calculated frontier molecular orbitals
      (FMOs) of Ar(iPr(4))GaGaAr(iPr(4)) are of pi-pi symmetry, allowing this molecule
      to engage in a wider range of reactions than permitted by the usual pi-pi* FMOs
      of C-C pi bonds or the pi-n(+) FMOs of heavier group 14 alkyne analogues.

PMID- 22420621
TI  - Exorcising the exocyst complex.
AB  - The exocyst complex is an evolutionarily conserved multisubunit protein complex
      implicated in tethering secretory vesicles to the plasma membrane. Originally
      identified two decades ago in budding yeast, investigations using several
      different eukaryotic systems have since made great progress toward determination
      of the overall structure and organization of the eight exocyst subunits. Studies
      point to a critical role for the complex as a spatiotemporal regulator through
      the numerous protein and lipid interactions of its subunits, although a molecular
      understanding of exocyst function has been challenging to elucidate. Recent
      progress demonstrates that the exocyst is also important for additional
      trafficking steps and cellular processes beyond exocytosis, with links to
      development and disease. In this review, we discuss current knowledge of exocyst
      architecture, assembly, regulation and its roles in a variety of cellular
      trafficking pathways.

PMID- 22420623
TI  - Postpartum aHUS secondary to a genetic abnormality in factor H acquired through
      liver transplantation.
AB  - We report here a young female who underwent a successful deceased donor liver
      transplant for hepatic vein thrombosis. Five years after transplantation she
      developed postpartum atypical hemolytic uremic syndrome (aHUS). She did not
      recover renal function. Mutation screening of complement genes in her DNA did not
      show any abnormality. Mutation screening of DNA available from the donor showed a
      nonsense CFH mutation leading to factor H deficiency. Genotyping of the patient
      showed that she was homozygous for an aHUS CD46 at-risk haplotype. In this
      individual, the development of aHUS has been facilitated by the combination of a
      trigger (pregnancy), an acquired rare genetic variant (CFH mutation) and a common
      susceptibility factor (CD46 haplotype).

PMID- 22420624
TI  - Thermal isomerizations of cis,anti,cis-tricyclo[7.4.0.0(2,8)]tridec-10-ene.
AB  - cis,anti,cis-Tricyclo[7.4.0.0(2,8)]tridec-10-ene (13TCT) undergoes [1,3]
      sigmatropic rearrangements at 315  degrees C in the gas phase to the si product 1
      and to the sr product 2 with si/sr = 2.1. The dominant thermal isomerization
      process, however, is epimerization at C8 to afford product 3. That stereomutation
      at C8 occurs 50% faster than the si and sr shifts combined.

PMID- 22420625
TI  - Noggin on heaven's door: a factor that promotes the selective production of
      serotonergic neurons from murine embryonic stem cells and induced pluripotent
      stem cells.

PMID- 22420626
TI  - Design of beta-amyloid aggregation inhibitors from a predicted structural motif.
AB  - Drug design studies targeting one of the primary toxic agents in Alzheimer's
      disease, soluble oligomers of amyloid beta-protein (Abeta), have been complicated
      by the rapid, heterogeneous aggregation of Abeta and the resulting difficulty to
      structurally characterize the peptide. To address this, we have developed
      [Nle(35), D-Pro(37)]Abeta(42), a substituted peptide inspired from molecular
      dynamics simulations which forms structures stable enough to be analyzed by NMR.
      We report herein that [Nle(35), D-Pro(37)]Abeta(42) stabilizes the trimer and
      prevents mature fibril and beta-sheet formation. Further, [Nle(35), D
      Pro(37)]Abeta(42) interacts with WT Abeta(42) and reduces aggregation levels and
      fibril formation in mixtures. Using ligand-based drug design based on [Nle(35), D
      Pro(37)]Abeta(42), a lead compound was identified with effects on inhibition
      similar to the peptide. The ability of [Nle(35), D-Pro(37)]Abeta(42) and the
      compound to inhibit the aggregation of Abeta(42) provides a novel tool to study
      the structure of Abeta oligomers. More broadly, our data demonstrate how
      molecular dynamics simulation can guide experiment for further research into AD.

PMID- 22420627
TI  - Polycystic ovary syndrome: brain-derived neurotrophic factor (BDNF) plasma and
      follicular fluid levels.
AB  - Polycystic ovary syndrome is one of the most common endocrine disorders in women
      of reproductive age. Features of PCOS are hyperandrogenism, chronic anovulation
      and polycystic ovaries on ultrasonography. Follicle development is a complex and
      carefully orchestrated phenomenon, involving gonadotropins and a rapidly
      expanding list of other intraovarian regulators, such as brain-derived
      neurotrophic factor (BDNF). The aim of this study is to evaluate BDNF in plasma
      and in follicular fluid in women affected by PCOS and in normal menstruating
      women. In PCOS patients the BDNF levels in plasma and in follicular fluid are
      higher than values obtained in healthy controls. Therefore we can hypothsize that
      high levels of luteinizing hormone, probably increase the secretion of BDNF in
      PCOS patients.

PMID- 22420628
TI  - Breast carcinomas with hyperprolactinemia at the time of diagnosis-clinico
      biological association.
AB  - AIM: To analyse association between preoperative hyperprolactinemia serum levels
      and clinical and biological features of breast tumors. METHODS: Serum levels of
      prolactin were measured in 253 women with invasive breast cancer. Clinical and
      biological parameters analysed were age, size, lymph node involvement, distant
      metastasis and immunohistochemical expression of estrogen receptor, progesterone
      receptor, androgen receptor, bcl-2, p53 and Ki67. RESULTS: In ductal carcinomas
      hyperprolactinemia were associated with high age (p = 0.017), and with bcl-2 + +
      + expression (p = 0.017). Furthermore, serum prolactin values were significantly
      higher in bcl-2 +++ cases vs negative (p = 0.029); the same happened when we
      considered the positivity threshold of 25 ng/mL (p = 0.015). CONCLUSION: Is
      possible to detect in 6% of infiltrating ductal breast carcinomas
      hyperprolactinemia (>25 ng/mL), being associated only with increasing age, but
      not with other clinical or biological factors; and 2) the most surprising data
      was the association between prolactinemia (qualitative (>25 ng/mL) and
      quantitative) and intense bcl-2 tissue expression, which suggests that, probably,
      this (prolactinemia) is not a sign of worse prognosis and evolution.

PMID- 22420629
TI  - The Rome II and Rome III criteria identify the same subtype-populations in
      irritable bowel syndrome: agreement depends on the method used for symptom
      report.
AB  - BACKGROUND: For comparing trials using different classifications for irritable
      bowel syndrome (IBS) subtypes, it is important to know whether these identify the
      same sub-populations. Our aim was to determine the agreement between Rome II and
      Rome III subtypes, and to explore whether agreement depends on the symptom
      reporting method. METHODS: Rome II IBS patients from two identical, randomized
      placebo-controlled trials of probiotics were included. Retrospective subtypes
      were based on the Rome II questionnaire. Prospective subtypes were based on diary
      cards for 2 weeks of run-in. Agreement was determined between: (i) retrospective
      Rome II and Rome III, (ii) prospective Rome II and Rome III, (iii) retrospective
      Rome II and prospectively Rome III, (iv) retrospective and prospective Rome II,
      and (v) retrospective and prospective Rome III. KEY RESULTS: A total of 126
      patients, 72% women, mean age 46 +/- 15 years, were included. The agreement
      between subtypes using the same symptom reporting method was: (i) 90.3% (kappa =
      0.85) for retrospective subtypes, and (ii) 84% (kappa = 0.76) for prospective
      subtypes. The agreement between subtypes using different symptom reporting
      methods was, (iii) 49% (kappa = 0.23) for retrospective Rome II and prospective
      Rome III, (iv) 51% (kappa = 0.26) for Rome II subtypes, and (v) 41% (kappa =
      0.25) for Rome III subtypes. CONCLUSIONS & INFERENCES: Agreement between Rome II
      and Rome III subtypes is good to very good when using the same symptom reporting
      method. When mixing methods, agreement is only fair even within the same
      classification. This has implications for comparison of trials using different
      symptom reporting methods for subtyping.

PMID- 22420630
TI  - Pneumatization of the skull base due to valsalva maneuver.
AB  - Objectives : We herewith report the case of a 43-year-old patient who experienced
      a skull base fracture associated with minimal trauma. The computed tomography
      scan examination showed unusual extensive pneumatization of the skull base. This
      patient used to perform repeated Valsalva maneuvers on a daily basis since
      childhood. Methods : A literature search and analysis of pneumatization
      mechanisms was performed. Results : Extensive skull base pneumatization has
      already been reported in patients performing daily Valsalva maneuver. Two
      pathogenic hypotheses are discussed: the bone cavity expansion through
      communicating spaces and cavitation secondary to increased intra-osseous pressure
      transmitted via the venous network with subsequent bone marrow ischemia.
      Conclusion : Valsalva maneuver may be the cause of an extensive skull base
      pneumatization. We hypothesize that the Valsalva maneuver may induce bone marrow
      ischemia that may, if repeated and prolonged, lead to pneumatization.

PMID- 22420631
TI  - Accelerated hypofractionated radiation therapy compared to conventionally
      fractionated radiation therapy for the treatment of inoperable non-small cell
      lung cancer.
AB  - BACKGROUND: While conventionally fractionated radiation therapy alone is an
      acceptable option for poor prognostic patients with unresectable stage III NSCLC,
      we hypothesized that accelerated hypofractionated radiotherapy will have similar
      efficacy without increasing toxicity. METHODS: This is a retrospective analysis
      of 300 patients diagnosed with stage III NSCLC treated between 1993 and 2009.
      Patients included in the study were medically or surgically inoperable, were free
      of metastatic disease at initial workup and did not receive concurrent
      chemotherapy. Patients were categorized into three groups. Group 1 received 45 Gy
      in 15 fractions over 3 weeks (Accelerated Radiotherapy (ACRT)) while group 2
      received 60-63 Gy (Standard Radiation Therapy 1 (STRT1)) and group 3 received >
      63 Gy (Standard Radiation Therapy (STRT2)). RESULTS: There were 119 (39.7%)
      patients in the ACRT group, 90 (30.0%) in STRT1 and 91 (30.3%) in STRT2. More
      patients in the ACRT group had KPS <= 60 (p < 0.001), more commonly presented
      with weight loss > 5% (p = 0.002), and had stage 3B disease (p < 0.001). After
      adjusting for clinical variables, there were no differences in the radiation
      groups in terms of the patterns of local or distant tumor control or overall
      survival. Some benefit in relapse free survival was seen in the STRT1 group as
      compared to ACRT (HR = 0.65, p = 0.011). Acute toxicity profiles in the ACRT were
      significantly lower for grade >= 2 radiation dermatitis (p = 0.002),
      nausea/vomiting (p = 0.022), and weight loss during treatment (p = 0.020).
      CONCLUSIONS: Despite the limitations of a retrospective analysis, our experience
      of accelerated hypofractionated radiation therapy with 45 Gy in 15 fractions
      appears to be an acceptable treatment option for poor performance status patients
      with stage III inoperable tumors. Such a treatment regimen (or higher doses in 15
      fractions) should be prospectively evaluated using modern radiation technologies
      with the addition of sequential high dose chemotherapy in stage III NSCLC.

PMID- 22420632
TI  - Exposure to toxic metals and persistent organic pollutants in Inuit children
      attending childcare centers in Nunavik, Canada.
AB  - Arctic populations are exposed to substantial levels of environmental
      contaminants that can negatively affect children's health and development.
      Moreover, emerging contaminants have never been assessed in Inuit children. In
      this study, we document the biological exposure to toxic metals and legacy and
      emerging persistent organic pollutants (POPs) of 155 Inuit children (mean age
      25.2 months) attending childcare centers in Nunavik. Blood samples were analyzed
      to determine concentrations of mercury, lead, polychlorinated biphenyls (PCBs),
      pesticides, brominated flame retardants [e.g., polybrominated diphenyl ethers
      (PBDEs)] and perfluoroalkyl and polyfluoroalkyl substances [PFASs; e.g.
      perfluorooctanesulfonate (PFOS) and perfluorooctane (PFOA)]. Lead [geometric mean
      (GM) 0.08 MUmol/L], PCB-153 (GM 22.2 ng/g of lipid), BDE-47 (GM 184 ng/g of
      lipid), PFOS (GM 3369 ng/L), and PFOA (GM 1617 ng/L) were detected in all
      samples. Mercury (GM 9.8 nmol/L) was detected in nearly all blood samples (97%).
      Levels of metals and legacy POPs are consistent with the decreasing trend
      observed in Nunavik and in the Arctic. PBDE levels were higher than those
      observed in many children and adolescents around the world but lower than those
      reported in some U.S. cities. PFOS were present in lower concentrations than in
      Nunavimmiut adults. There is a clear need for continued biomonitoring of blood
      contaminant levels in this population, particularly for PBDEs and PFASs.

PMID- 22420633
TI  - Acquisition of human alveolar bone-derived stromal cells using minimally
      irrigated implant osteotomy: in vitro and in vivo evaluations.
AB  - OBJECTIVES: Implant osteotomy yields a substantial amount of bone in the form of
      bone chips entrapped within drill flutes, and can provide a promising cell source
      for tissue engineering. The aims of this study were to isolate human alveolar
      bone-derived stromal cells (hABCs) obtained during implant osteotomy, and to
      evaluate osteogenic differentiation capacity of hABCs. MATERIAL AND METHODS: Bone
      chips were obtained by minimally irrigated implant drilling technique from 10
      human donors. Isolated cells were studied with respect to their colony-forming
      efficiency, surface marker expression by immunofluorescence staining,
      fluorescence-activated cell sorting analysis and self-renewal potency. To verify
      the differentiation activity, in vitro osteogenic and adipogenic gene expressions
      were evaluated by reverse transcription-polymerase chain reaction, and in vitro
      formation of mineralized nodule and adipocytes was also evaluated. In vivo bone
      forming activity was assessed by ectopic transplantation in immunocompromised
      mice (n = 5). RESULTS: Human alveolar bone-derived stromal cells population with
      characteristics of mesenchymal stem cells was present in the isolated cells. Upon
      hABC transplantation, significant ectopic bone formation was induced with the
      characteristics of fully matured bone tissue. CONCLUSION: The data support the
      feasibility of using hABCs as a source of stem cells for dentoalveolar bone
      tissue reconstruction. The cell source has an advantage that the hABCs can be
      easily acquired during implant surgery.

PMID- 22420634
TI  - An isolable NHC-stabilized silylene radical cation: synthesis and structural
      characterization.
AB  - The silyl-substituted silylene-NHC complex bis(tri-tert-butylsilyl)silylene
      (1,3,4,5-tetramethylimidazol-2-ylidene) [((t)Bu(3)Si)(2)Si:<-NHC(Me), 2] was
      synthesized and isolated as air- and moisture-sensitive orange crystals by
      reductive debromination of the dibromosilane ((t)Bu(3)Si)(2)SiBr(2) (1) with 2.0
      equiv of KC(8) in the presence of NHC(Me). In addition, the silylene-NHC complex
      2 cleanly underwent one-electron oxidation with 1.0 equiv of Ph(3)C(+).Ar(4)B(-)
      (Ar(4)B(-) = tetrakis[4-(tert-butyldimethylsilyl)-2,3,5,6
      tetrafluorophenyl]borate) in benzene to afford the NHC-stabilized silylene
      radical cation [((t)Bu(3)Si)(2)Si<-NHC(Me)](*+).Ar(4)B(-) (3). The radical cation
      3 was isolated as air- and moisture-sensitive yellow crystals and structurally
      characterized by X-ray crystallography and electron paramagnetic resonance
      spectroscopy, which showed that 3 has a planar structure with a pi-radical
      nature.

PMID- 22420635
TI  - Human papillomavirus vaccination is not exclusively a matter of price.

PMID- 22420636
TI  - Obesity and motor skills among 4 to 6-year-old children in the United States:
      nationally-representative surveys.
AB  - BACKGROUND: Few population-based studies have assessed relationships between body
      weight and motor skills in young children. Our objective was to estimate the
      association between obesity and motor skills at 4 years and 5-6 years of age in
      the United States. We used repeated cross-sectional assessments of the national
      sample from the Early Childhood Longitudinal Survey-Birth Cohort (ECLS-B) of
      preschool 4-year-old children (2005-2006; n = 5 100) and 5-6-year-old
      kindergarteners (2006-2007; n = 4 700). Height, weight, and fine and gross motor
      skills were assessed objectively via direct standardized procedures. We used
      categorical and continuous measures of body weight status, including obesity
      (Body Mass Index (BMI) >= 95th percentile) and BMI z-scores. Multivariate
      logistic and linear models estimated the association between obesity and gross
      and fine motor skills in very young children adjusting for individual, social,
      and economic characteristics and parental involvement. RESULTS: The prevalence of
      obesity was about 15%. The relationship between motor skills and obesity varied
      across types of skills. For hopping, obese boys and girls had significantly lower
      scores, 20% lower in obese preschoolers and 10% lower in obese kindergarteners
      than normal weight counterparts, p < 0.01. Obese girls could jump 1.6-1.7 inches
      shorter than normal weight peers (p < 0.01). Other gross motor skills and fine
      motor skills of young children were not consistently related to BMI z-scores and
      obesity. CONCLUSIONS: Based on objective assessment of children's motor skills
      and body weight and a full adjustment for confounding covariates, we find no
      reduction in overall coordination and fine motor skills in obese young children.
      Motor skills are adversely associated with childhood obesity only for skills most
      directly related to body weight.

PMID- 22420637
TI  - Chemoselective photodeoxidization of graphene oxide using sterically hindered
      amines as catalyst: synthesis and applications.
AB  - We report a green and efficient method for chemoselective deoxidization of
      graphene oxide via the ultraviolet irradiation catalyzed with 2,2,6,6-tetramethyl
      4-piperidinol. While the sp(2)-hybridized oxygen functional groups are removed
      after the reduction, the epoxy and hydroxyl groups are retained in the
      chemoselectively reduced graphene oxide (CrGO). The obtained CrGO nanosheets
      exhibit the high solubility and excellent electronic stability, which allows for
      the fabrication of thin film devices through a solution processing. As a proof of
      concept, a CrGO-based write-once-read-many-times memory device with the desirable
      stability and long-time operation is fabricated.

PMID- 22420638
TI  - PAMAM dendrimer-drug interactions: effect of pH on the binding and release
      pattern.
AB  - Understanding the dendrimer-drug interaction is of great importance to design and
      optimize the dendrimer-based drug delivery system. Using atomistic molecular
      dynamics (MD) simulations, we have analyzed the release pattern of four ligands
      (two soluble drugs, namely, salicylic acid (Sal), L-alanine (Ala), and two
      insoluble drugs, namely, phenylbutazone (Pbz) and primidone (Prim)), which were
      initially encapsulated inside the ethylenediamine (EDA) cored polyamidoamine
      (PAMAM) dendrimer using the docking method. We have computed the potential of
      mean force (PMF) variation with generation 5 (G5)-PAMAM dendrimer complexed with
      drug molecules using umbrella sampling. From our calculated PMF values, we
      observe that soluble drugs (Sal and Ala) have lower energy barriers than
      insoluble drugs (Pbz and Prim). The order of ease of release pattern for these
      drugs from G5 protonated PAMAM dendrimer was found to be Ala > Sal > Prim > Pbz.
      In the case of insoluble drugs (Prim and Pbz), because of larger size, we observe
      much nonpolar contribution, and thus, their larger energy barriers can be
      reasoned to van der Waals contribution. From the hydrogen bonding analysis of the
      four PAMAM-drug complexes under study, we found intermolecular hydrogen bonding
      to show less significant contribution to the free energy barrier. Another
      interesting feature appears while calculating the PMF profile of G5NP
      (nonprotonated)-PAMAM-Pbz and G5NP (nonprotonated)-PAMAM-Sal complex. The PMF was
      found to be less when the drug is bound to nonprotonated dendrimer compared to
      the protonated dendrimer. Our results suggest that encapsulation of the drug
      molecule into the host PAMAM dendrimer should be carried out at higher pH values
      (near pH 10). When such complex enters the human body, the pH is around 7.4 and
      at that physiological pH, the dendrimer holds the drug tightly. Hence the release
      of drug can occur at a controlled rate into the bloodstream. Thus, our findings
      provide a microscopic picture of the encapsulation and controlled release of
      drugs in the case of dendrimer-based host-guest systems.

PMID- 22420639
TI  - Corporate image and public health: an analysis of the Philip Morris, Kraft, and
      Nestle websites.
AB  - Companies need to maintain a good reputation to do business; however, companies
      in the infant formula, tobacco, and processed food industries have been
      identified as promoting disease. Such companies use their websites as a means of
      promulgating a positive public image, thereby potentially reducing the
      effectiveness of public health campaigns against the problems they perpetuate.
      The author examined documents from the websites of Philip Morris, Kraft, and
      Nestle for issue framing and analyzed them using Benoit's typology of corporate
      image repair strategies. All three companies defined the problems they were
      addressing strategically, minimizing their own responsibility and the
      consequences of their actions. They proposed solutions that were actions to be
      taken by others. They also associated themselves with public health
      organizations. Health advocates should recognize industry attempts to use
      relationships with health organizations as strategic image repair and reject
      industry efforts to position themselves as stakeholders in public health
      problems. Denormalizing industries that are disease vectors, not just their
      products, may be critical in realizing positive change.

PMID- 22420640
TI  - High-throughput phenotyping and genomic selection: the frontiers of crop breeding
      converge.
AB  - Genomic selection (GS) and high-throughput phenotyping have recently been
      captivating the interest of the crop breeding community from both the public and
      private sectors world-wide. Both approaches promise to revolutionize the
      prediction of complex traits, including growth, yield and adaptation to stress.
      Whereas high-throughput phenotyping may help to improve understanding of crop
      physiology, most powerful techniques for high-throughput field phenotyping are
      empirical rather than analytical and comparable to genomic selection. Despite the
      fact that the two methodological approaches represent the extremes of what is
      understood as the breeding process (phenotype versus genome), they both consider
      the targeted traits (e.g. grain yield, growth, phenology, plant adaptation to
      stress) as a black box instead of dissecting them as a set of secondary traits
      (i.e. physiological) putatively related to the target trait. Both GS and high
      throughput phenotyping have in common their empirical approach enabling breeders
      to use genome profile or phenotype without understanding the underlying biology.
      This short review discusses the main aspects of both approaches and focuses on
      the case of genomic selection of maize flowering traits and near-infrared
      spectroscopy (NIRS) and plant spectral reflectance as high-throughput field
      phenotyping methods for complex traits such as crop growth and yield.

PMID- 22420641
TI  - New directions in cellular therapy of cancer: a summary of the summit on cellular
      therapy for cancer.
AB  - A summit on cellular therapy for cancer discussed and presented advances related
      to the use of adoptive cellular therapy for melanoma and other cancers. The
      summit revealed that this field is advancing rapidly. Conventional cellular
      therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more
      effective and more available. Gene therapy is becoming an important tool in
      adoptive cell therapy. Lymphocytes are being engineered to express high affinity
      T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines.
      T cell subsets with more naive and stem cell-like characteristics have been shown
      in pre-clinical models to be more effective than unselected populations and it is
      now possible to reprogram T cells and to produce T cells with stem cell
      characteristics. In the future, combinations of adoptive transfer of T cells and
      specific vaccination against the cognate antigen can be envisaged to further
      enhance the effectiveness of these therapies.

PMID- 22420643
TI  - Structure of triplex DNA in the gas phase.
AB  - Extensive (more than 90 microseconds) molecular dynamics simulations complemented
      with ion-mobility mass spectrometry experiments have been used to characterize
      the conformational ensemble of DNA triplexes in the gas phase. Our results
      suggest that the ensemble of DNA triplex structures in the gas phase is well
      defined over the experimental time scale, with the three strands tightly bound,
      and for the most abundant charge states it samples conformations only slightly
      more compact than the solution structure. The degree of structural alteration is
      however very significant, mimicking that found in duplex and much larger than
      that suggested for G-quadruplexes. Our data strongly supports that the gas phase
      triplex maintains an excellent memory of the solution structure, well-preserved
      helicity, and a significant number of native contacts. Once again, a linear,
      flexible, and charged polymer as DNA surprises us for its ability to retain three
      dimensional structure in the absence of solvent. Results argue against the
      generally assumed roles of the different physical interactions (solvent screening
      of phosphate repulsion, hydrophobic effect, and solvation of accessible polar
      groups) in modulating the stability of DNA structures.

PMID- 22420642
TI  - Colonic inflammation up-regulates voltage-gated sodium channels in bladder
      sensory neurons via activation of peripheral transient potential vanilloid 1
      receptors.
AB  - BACKGROUND: Primary sensory neurons express several types of ion channels
      including transient receptor potential vanilloid 1 (TRPV1) and voltage-gated
      Na(+) channels. Our previous studies showed an increased excitability of bladder
      primary sensory and spinal neurons triggered by inflammation in the distal colon
      as a result of pelvic organ cross-sensitization. The goal of this work was to
      determine the effects of TRPV1 receptor activation by potent agonists and/or
      colonic inflammation on voltage-gated Na(+) channels expressed in bladder sensory
      neurons. METHODS: Sprague-Dawley rats were treated with intracolonic saline
      (control), resiniferatoxin (RTX, 10(-7 ) mol L(-1)), TNBS (colonic irritant) or
      double treatment (RTX followed by TNBS). KEY RESULTS: TNBS-induced colitis
      increased the amplitude of total Na(+) current by two-fold and of tetrodotoxin
      resistant (TTX-R) Na(+) current by 78% (P <= 0.05 to control) in lumbosacral
      bladder neurons during acute phase (3 days post-TNBS). Instillation of RTX in the
      distal colon caused an enhancement in the amplitude of total Na(+) current at -20
      mV from -112.1 +/- 18.7 pA/pF (control) to -183.6 +/- 27.8 pA/pF (3 days post
      RTX, P <= 0.05) without changes in TTX resistant component. The amplitude of net
      Na(+) current was also increased by 119% at day 3 in the group with double
      treatment (RTX followed by TNBS, P <= 0.05 to control) which was significantly
      higher than in either group with a single treatment. CONCLUSIONS & INFERENCES:
      These results provide evidence that colonic inflammation activates TRPV1
      receptors at the peripheral sensory terminals leading to an up-regulation of
      voltage gated Na(+) channels on the cell soma of bladder sensory neurons. This
      mechanism may underlie the occurrence of peripheral cross-sensitization in the
      pelvis and functional chronic pelvic pain.

PMID- 22420644
TI  - Dickkopf-1 inhibits the invasive activity of melanoma cells.
AB  - BACKGROUND: Malignant melanoma (MM) has the highest morbidity of any malignant
      tumour. It is known that the Wnt pathway of enhances the development of melanoma.
      Dickkopf (DKK)-1, an inhibitor of the canonical Wnt/beta-catenin pathway, might
      also inhibit the development of MM. AIM: To examine the influence of DKK-1
      expression on the invasive activity of MM cells. METHODS: To detect DKK-1
      expression level we performed immunohistochemistry on human tissue sections of
      normal skin, malignant melanoma (MM) in situ, and MM with lymph-node metastasis.
      To clarify the role that DDK-1 plays in the invasive activity of MM cells, we
      performed a scratch-wound healing assay and Transwell invasion assay for A375
      cells infected with appropriate recombinant adenoviruses, then assessed the
      migration of these cells. RESULTS: Fewer DDK1-overexpressing A375 cells than
      control cells migrated to the scratch-wound area or through the pores of the
      Transwell membrane to the lower wells. Downregulation of DKK-1 in A375 cells had
      the opposite effect. CONCLUSIONS: In the present study, we found for the first
      time that DKK-1 expression inhibits the invasive activity of MM cells.

PMID- 22420645
TI  - Combined spinal epidural vs epidural labour analgesia: does initial intrathecal
      analgesia reduce the subsequent minimum local analgesic concentration of epidural
      bupivacaine?
AB  - Labour analgesia initiated using a combined spinal-epidural (CSE) technique may
      reduce subsequent epidural bupivacaine requirements compared with an epidural
      only technique. We compared the minimum local analgesic concentrations (MLAC) of
      epidural bupivacaine following initial intrathecal or epidural injection. In a
      prospective, double-blind study, 115 women requesting epidural analgesia were
      randomly assigned to receive either an epidural with bupivacaine 20 mg and
      fentanyl 40 MUg or a CSE with intrathecal bupivacaine 2.5 mg and fentanyl 5 MUg.
      Analgesia was assessed using a visual analogue pain score. When further analgesia
      was requested, bupivacaine 20 ml was given, and the concentration was determined
      using the technique of up-down sequential allocation. The MLAC of bupivacaine in
      the epidural group was 0.032% wt/vol (95% CI 0.020-0.044) compared with 0.047%
      wt/vol (95% CI 0.042-0.052) in the CSE group. Bupivacaine requirements for the
      second injection were increased following intrathecal analgesia by a factor of
      1.45 (p = 0.026) compared with epidural analgesia.

PMID- 22420646
TI  - A Rab11A/myosin Vb/Rab11-FIP2 complex frames two late recycling steps of langerin
      from the ERC to the plasma membrane.
AB  - A large body of knowledge relating to the constitution of Rab GTPase/Rab effector
      complexes and their impact on both membrane domain organization and overall
      membrane trafficking has been built up in recent years. However in the context of
      the live cell there are still many questions that remain to be answered, such as
      where and when these complexes assemble and where they perform their primary
      function(s). We describe here the dynamic processes that take place in the final
      steps of the Rab11A dependent recycling pathway, in the context of the membrane
      platform constituted by Myosin Vb, Rab11A, and Rab11-FIP2. We first confirm that
      a series of previously reported observations obtained during the study of a
      number of trafficking cargoes also apply to langerin. Langerin is a cargo
      molecule that traffics through Rab11A-positive membrane domains of the endosomal
      recycling pathway. In order to explore the relative dynamics of this set of
      partners, we make extensive use of a combinatory approach of Live-FRET, fast FRAP
      video, fast confocal and TIRF microscopy modalities. Our data show that the
      Myosin Vb/Rab11A/Rab11-FIP2 platform is spatially involved in the regulation of
      langerin trafficking at two distinct sites within live cells, first at the
      sorting site in the endosomal recycling compartment (ERC) where transport
      vesicles are formed, and subsequently, in a strict time-defined order, at the
      very late stage of docking/tethering and fusion of these langerin recycling
      vesicles to the plasma membrane.

PMID- 22420647
TI  - Palladium(0)-catalyzed allylic alkylation of diketoester-dioxinones with allyl
      acetates under neutral conditions: synthesis of hexasubstituted benzene
      derivatives.
AB  - Intermolecular palladium(0)-catalyzed allylic alkylation of diketoester
      dioxinones was performed under neutral conditions with 2-alkenyl and 2
      cycloalkenyl acetates. Subsequent aromatization using cesium carbonate gave rise
      to isopropylidene-protected hexasubstituted resorcylates.

PMID- 22420648
TI  - Inflammatory biomarkers in saliva: assessing the strength of association of
      diabetes mellitus and periodontal status with the oral inflammatory burden.
AB  - AIM: To determine the strength of association of type 2 diabetes mellitus and
      periodontal disease with the oral inflammatory burden, as assessed by markers of
      inflammation in saliva. MATERIAL AND METHODS: Unstimulated saliva samples were
      collected from 192 subjects with or without type 2 diabetes. beta-glucuronidase
      (betaG) was measured via a fluorometric array and interlukin-1beta (IL-1beta) via
      enzyme-linked immunosorbent assay. The concentration of both mediators was
      evaluated in relationship to clinical parameters, severity of periodontal disease
      and diabetes status. RESULTS: Regression analysis demonstrated that diabetes and
      periodontal disease was independently and positively correlated with increased
      concentration of betaG in saliva (p < 0.001). Moreover, the relative association
      of periodontal disease with the level of betaG in saliva was greater than the
      strength of association of the diabetic status. IL-1beta concentration in saliva
      was primarily associated with the severity of periodontal disease (p < 0.01), but
      not the presence of diabetes (p = 0.50). CONCLUSIONS: This study examined the
      nature of the inflammatory response in the oral cavity as assessed by
      inflammatory markers in saliva. Both periodontal disease and diabetes mellitus
      were independently associated with the oral inflammatory burden, in which the
      effect of periodontal disease was more pronounced.

PMID- 22420649
TI  - Systematic review of disease-modifying antirheumatic drugs for juvenile
      idiopathic arthritis.
AB  - BACKGROUND: Treatment of juvenile idiopathic arthritis (JIA) with disease
      modifying antirheumatic drugs (DMARDs) may improve outcomes compared to
      conventional therapy (e.g., non-steroidal anti-inflammatory drugs, intra
      articular corticosteroids). The purpose of this systematic review was to evaluate
      the comparative effectiveness and safety of DMARDs versus conventional therapy
      and versus other DMARDs. RESULTS: A systematic evidence review of 156 reports
      identified in MEDLINE(r), EMBASE(r), and by hand searches. There is some evidence
      that methotrexate is superior to conventional therapy. Among children who have
      responded to a biologic DMARD, randomized discontinuation trials suggest that
      continued treatment decreases the risk of having a flare. However, these studies
      evaluated DMARDs with different mechanisms of action (abatacept, adalimumab,
      anakinra, etanercept, intravenous immunoglobulin, tocilizumab) and used varying
      comparators and follow-up periods. Rates of serious adverse events are similar
      between DMARDs and placebo in published trials. This review identified 11
      incident cases of cancer among several thousand children treated with one or more
      DMARD. CONCLUSIONS: Few data are available to evaluate the comparative
      effectiveness of either specific DMARDs or general classes of DMARDs. However,
      based on the overall number, quality, and consistency of studies, there is
      moderate strength of evidence to support that DMARDs improve JIA-associated
      symptoms. Limited data suggest that short-term risk of cancer is low.

PMID- 22420650
TI  - Temperamental Differences in Children's Reactions to Peer Victimization.
AB  - This research examined the hypothesis that temperament and sex moderate the
      contribution of peer victimization to children's subsequent adjustment
      (aggression and depressive symptoms). Children (125 boys, 158 girls; M age = 7.95
      years, SD = 0.32; 77.7% White, 22.3% minority) and teachers reported on overt and
      relational victimization. Parents rated children's temperament (inhibitory
      control and negative emotionality) and depressive symptoms, and teachers reported
      on children's overt and relational aggression. Across a 1-year period, (a) overt
      victimization predicted overt aggression in girls with poor inhibitory control,
      (b) overt and relational victimization predicted depressive symptoms in girls
      with high negative emotionality, and (c) relational victimization predicted
      depressive symptoms in boys with low negative emotionality. This research helps
      to explain individual variation in children's reactions to peer victimization and
      has implications for Person * Environment models of development. Moreover, this
      research informs the development of targeted intervention programs for victimized
      youth that bolster specific resources depending on their temperament.

PMID- 22420651
TI  - HIV Co-receptor usage in HIV-related non-hodgkin's lymphoma.
AB  - In this study 15 banked samples of HIV-related Non-Hodgkin's Lymphoma (NHL)
      cases were tested for HIV co-receptor usage and SDF1 3'A polymorphism. Reportable
      tropism from 9 plasma samples had 1 (11.1%) HIV case with CXCR4 and 8 (88.9%)
      with CCR5 usage, even though most of the cases occurred at a late stage of HIV
      (2/3 had CD4 counts below 200), where expected CXCR4 usage would be 60%. Based on
      the expected proportion of less than 50% CCR5 in chronically infected
      individuals, this would suggest that in NHL may be associated with CCR5 usage (P
      = 0.04).

PMID- 22420652
TI  - NSAIDs: take with food or after fasting?
AB  - OBJECTIVE: Published and regulatory advice is to take NSAIDs with fluids and/or
      food irrespective whether NSAIDs are taken over the counter or long-term. The
      basis for this recommendation is not clear and we sought to establish the reasons
      for it through a search of published literature and personal files. RESULTS:
      Results from experimental animals show that fasting increases the gastric side
      effects of NSAIDs while food increases small bowel damage, but this has not been
      tested in humans. The possible effects of food in modifying the gastric damage
      caused by NSAIDs are complex, as food quantity and composition modify the
      responses substantially. Food usually delays peak levels of NSAIDs (and hence
      onset of action) without affecting total bioavailability. This may not be
      important when a steady state is achieved, but rapid onset of action is highly
      relevant for over-the-counter use of NSAIDs. The safety of over-the-counter use
      of ibuprofen and naproxen appears to be excellent and comparable with
      paracetamol. CONCLUSION: The rapid onset of action of NSAIDs is most important
      during over-the-counter use, in which case it may be more appropriate to take the
      drugs on a fasting stomach.

PMID- 22420653
TI  - Aliskiren as a novel therapeutic agent for hypertension and cardio-renal
      diseases.
AB  - OBJECTIVES: High blood pressure (BP) is a major risk factor for cardiovascular
      and renal complications. A majority of treated hypertensive patients still
      complain of high BP. The renin-angiotensin aldosterone system (RAAS) has been a
      centre-stage target for all the cardiovascular and cardio-renal complications.
      Aliskiren, is the first direct renin inhibitor (DRI) to be approved by the US
      FDA. Renin controls the rate-limiting step in the RAAS cascade and hence is the
      most favorable target for RAAS suppression. KEY FINDINGS: This review article
      strives to summarize the pharmacokinetic, preclinical and clinical studies done
      so far pertaining to the efficacy of aliskiren. Further, the pharmacology of
      aliskiren has been comprehensively dealt with to enhance understanding so as to
      further research in this unfathomed area in the multitude of cardiovascular
      disorders and renal diseases. SUMMARY: Aliskiren has been shown to have
      comparable BP-lowering effects to other RAAS inhibitors. Recent clinical trials
      have indicated that it might contribute significantly in combination with other
      agents for the protection of end-organ diseases.

PMID- 22420654
TI  - Reliable and effective oxygen-ozone therapy at a crossroads with ozonated saline
      infusion and ozone rectal insufflation.
AB  - OBJECTIVES: This review aims to highlight the advantages and safety of oxygen
      ozone therapy (OOT) and to suggest ways to enhance its acceptance. KEY FINDINGS:
      The treatment of a herniated disk by injecting a gaseous oxygen-ozone mixture
      inside the nucleus pulposus is a great clinical success. However, the use of OOT
      lags for a number of reasons, including lack of standardization, the need for
      numerous treatments, lack of knowledge and even denial. Anecdotally, several
      million treatments by OOT have been performed worldwide indicating its
      usefulness, mainly in peripheral arterial diseases and age-related macular
      degeneration. The scepticism that accompanies the systemic use of ozone can only
      be overcome by demonstrating the validity of OOT in controlled and randomized
      clinical trials. Cheaper and quicker methods, such as ozonating physiological
      saline with successive infusion as well as ozone rectal insufflations, are
      becoming popular, however, such alternative procedures are erratic, unstable and
      liable to be toxic, with deleterious consequences, and are likely to discredit
      the beneficial use of ozone. SUMMARY: The approval of ozone in terms of both
      therapeutic efficacy and safety will depend on the results achieved by
      authoritative clinical trials.

PMID- 22420655
TI  - Size estimation of chemical space: how big is it?
AB  - OBJECTIVES: To estimate the size of organic chemical space and its sub-regions,
      i.e. drug-like chemical space and known drug space (KDS). METHODS: Analysis of
      the growth of organic compounds as a function of their carbon atoms based on a
      power function (f(x)=A*B, C=x) and an exponential function (f(x)=AeBx). Also, the
      statistical distribution of KDS and drug-like chemical space (drugs with good
      oral-bioavailability) based on their carbon atom count was used to deduce their
      size. KEY FINDINGS: The power function (f(x)=A*B, C=x) gives a superior fit to
      the growth of organic compounds leading to an estimate of 3.4*109 populating
      chemical space. KDS is predicted to be 2.0*106 molecules and drug-like chemical
      space is calculated to be 1.1*106 compounds. CONCLUSIONS: The values here are
      much smaller than previously reported. However, the numbers are large but not
      astronomical. A clear rationale on how we reach these numbers is given, which
      hopefully will lead to more refined predictions.

PMID- 22420656
TI  - Etoposide modulates the effects of oral morphine analgesia by targeting the
      intestinal P-glycoprotein.
AB  - OBJECTIVES: Opioids and anticancer compounds such as etoposide (ETP) are
      substrates of P-glycoprotein (P-gp), an ATP-dependent efflux pump. Chemotherapy
      compounds may impact on the analgesic effect of opioids such as morphine when the
      two drugs are co-administered. In this study, we used a mouse model to determine
      if there is a pharmacological interaction between ETP and morphine, focusing on
      the involvement of intestinal P-gp. METHODS: P-gp drug efflux activity was
      measured by an in-situ closed loop method with Rhodamine 123, a P-gp substrate.
      The analgesic effect of morphine was determined by the tail-flick test.
      Intestinal P-gp expression levels were determined by Western blot. KEY FINDINGS:
      ETP and morphine significantly decreased the intestinal Rhodamine 123 efflux
      activity of P-gp. Oral morphine analgesia was significantly enhanced when co
      administered with ETP. However, repeated pretreatment (7 days) with oral ETP
      significantly decreased the oral morphine-induced analgesia, in a cyclosporine A
      (a P-gp inhibitor) reversible manner. Furthermore, repeated ETP significantly up
      regulated intestinal P-gp expression. CONCLUSIONS: It may be important to
      consider aspects of therapeutic design such as the administration route or
      scheduling of drugs in patients receiving concurrent chemotherapy and opioid
      therapy to avoid pharmacokinetic interactions between the two agents.

PMID- 22420657
TI  - Development of a gastroretentive pulsatile drug delivery platform.
AB  - OBJECTIVES: To develop a novel gastroretentive pulsatile drug delivery platform
      by combining the advantages of floating dosage forms for the stomach and
      pulsatile drug delivery systems. METHODS: A gastric fluid impermeable capsule
      body was used as a vessel to contain one or more drug layer(s) as well as one or
      more lag-time controlling layer(s). A controlled amount of air was sealed in the
      innermost portion of the capsule body to reduce the overall density of the drug
      delivery platform, enabling gastric floatation. An optimal mass fill inside the
      gastric fluid impermeable capsule body enabled buoyancy in a vertical orientation
      to provide a constant surface area for controlled erosion of the lag-time
      controlling layer. The lag-time controlling layer consisted of a swellable
      polymer, which rapidly formed a gel to seal the mouth of capsule body and act as
      a barrier to gastric fluid ingress. KEY FINDINGS: By varying the composition of
      the lag-time controlling layer, it was possible to selectively program the onset
      of the pulsatile delivery of a drug. CONCLUSIONS: This new delivery platform
      offers a new method of delivery for a variety of suitable drugs targeted in
      chronopharmaceutical therapy. This strategy could ultimately improve drug
      efficacy and patient compliance, and reduce harmful side effects by scaling back
      doses of drug administered.

PMID- 22420658
TI  - The CAM-LDPI method: a novel platform for the assessment of drug absorption.
AB  - OBJECTIVES: This study aimed to explore the use of the chicken chorioallantoic
      membrane (CAM) with laser doppler perfusion imaging (LDPI) as a platform to
      assess absorption of vasoactive drugs. METHODS: The optimal age of the CAM to be
      employed in the test and the indicator of vasoactivity were first established.
      Test substances that included common solvents and vasoactive drugs were tested on
      the CAM surface to determine their irritancy and blood perfusion effects. KEY
      FINDINGS: Insignificant changes in blood perfusion were observed with deionized
      water, 0.9% w/v soldium chloride and 5% w/v glucose monohydrate, as well as
      theophylline and glucagon. Complex changes in blood perfusion were detected with
      ethanol, N-methyl-2-pyrrolidone, glycerin and propranolol. Both caffeine and
      glyceryl trinitrate resulted in a drop in blood perfusion. CONCLUSIONS: It was
      concluded that the LDPI offers a rapid and non-invasive method to measure blood
      perfusion in the CAM. The latter provides a potentially useful platform in
      formulation studies to evaluate the effects of additives on drug absorption using
      caffeine or glyceryl trinitrate as model drugs.

PMID- 22420659
TI  - Novel interpenetrated polymer network microbeads of natural polysaccharides for
      modified release of water soluble drug: in-vitro and in-vivo evaluation.
AB  - OBJECTIVES: The objective of this work was to prepare novel interpenetrating
      polymer network (IPN) microbeads of tamarind seed polysaccharide and sodium
      alginate for controlled release of the water soluble drug, diltiazem
      hydrochloride. METHODS: The diltiazem-Indion 254((r)) (a cation exchange resin)
      complex was prepared and the resulting complex was entrapped within IPN
      microbeads prepared by ionotropic gelation and covalent crosslinking. Microbeads
      were characterized by scanning electron microscopy, differential scanning
      calorimetry, thermogravimetric analysis, X-ray diffraction and Fourier transform
      infrared spectroscopy (FTIR) analyses, and evaluated for swelling, in-vitro
      release and preclinical pharmacokinetics. KEY FINDINGS: The unformulated drug
      showed complete dissolution within 60min, while drug release from diltiazem-ion
      exchange resin complex was extended for 2.5h but IPN microbeads extended the
      release for longer period. The ionically crosslinked microbeads released the drug
      for 6h, while dual crosslinked microbeads extended the release for 9h. The
      microbeads containing a higher amount of glutaraldehyde released the drug very
      slowly. The results of in-vivo pharmacokinetics of pure drug and drug-loaded IPN
      microbeads showed that the microbeads demonstrated prolonged release supporting
      the findings of in-vitro studies. CONCLUSIONS: Prepared IPN microbeads showed
      prolonged in-vitro and in-vivo release for diltiazem, indicating that this IPN
      would be a versatile delivery system for water soluble drugs.

PMID- 22420660
TI  - Absorption enhancement studies of clopidogrel hydrogen sulphate in rat everted
      gut sacs.
AB  - OBJECTIVES: Clopidogrel, a thienopyridine antiplatelet agent, is a poor aqueous
      soluble compound and a P-glycoprotein (P-gp) efflux pump substrate. These two
      factors are responsible for its incomplete intestinal absorption. In this study,
      we have attempted to enhance the absorption of clopidogrel by improving its
      solubility and by inhibiting intestinal P-gp activity. METHODS:   Solubility
      enhancement was achieved by preparing solid dispersions. Quinidine and naringin
      were selected as P-gp inhibitors, whilst tartaric acid was selected as the
      intestinal absorption enhancer. Absorption studies were performed using the
      everted gut sac model prepared from rat jejunum. The determination of clopidogrel
      was performed by high performance liquid chromatography. KEY FINDINGS: We noticed
      an enhancement of clopidogrel absorption by improving its solubility or by
      inhibiting the P-gp activity. The greatest results were obtained for solid
      dispersions in the presence of P-gp inhibitors at their highest concentrations,
      with an absorption improvement of 3.41- and 3.91-fold for naringin (15mg/kg) and
      quinidine (200um), respectively. However, no clopidogrel absorption enhancement
      occurred in the presence of tartaric acid. CONCLUSIONS: Naringin, a natural
      compound which has no undesirable side effects as compared with quinidine, could
      be used as a pharmaceutical excipient in the presence of clopidogrel solid
      dispersions to increase clopidogrel intestinal absorption and therefore its oral
      bioavailability.

PMID- 22420661
TI  - Reversible and pH-dependent weak drug-excipient binding does not affect oral
      bioavailability of high dose drugs.
AB  - OBJECTIVES: Drug-excipient binding can affect in-vitro drug release. Literature
      suggests that drug-excipient ionic binding interaction that is not disrupted by
      physiological salt concentration in the dissolution medium can impact a drug's
      oral bioavailability. We investigated whether nondisruption of interaction by
      physiological salt concentration was an adequate predictor of its biorelevance
      using the binding of a model amine high dose drug brivanib alaninate (BA) to
      croscarmellose sodium (CCS) as an example. METHODS: BA was formulated into an
      immediate release tablet using CCS as disintegrant by a wet granulation process.
      In-vitro drug release was carried out as a function of pH and buffer
      concentration of the medium. BA-CCS binding was studied in buffer solution and
      data fitted to a Langmuir isotherm. A simulation model and an isothermal
      titration calorimetry method were developed to assess the bioavailability risk
      and strength of drug-excipient binding interaction, independent of physiological
      salt concentration consideration. KEY FINDINGS: BA-CCS binding was pH-dependent,
      reversible, ionic, and not disrupted by increasing the buffer concentration in
      the dissolution medium. Absorption simulation predictions of no effect of CCS
      binding on BA's bioavailability were confirmed by a monkey pharmacokinetic study.
      CONCLUSIONS: A pH-dependent and reversible weak drug-excipient binding
      interaction is unlikely to affect the oral bioavailability of high dose drugs.

PMID- 22420662
TI  - An evaluation of the potential of linear and nonlinear skin permeation models for
      the prediction of experimentally measured percutaneous drug absorption.
AB  - OBJECTIVES  The developments in combinatorial chemistry have led to a rapid
      increase in drug design and discovery and, ultimately, the production of many
      potential molecules that require evaluation. Hence, there has been much interest
      in the use of mathematical models to predict dermal absorption. Therefore, the
      aim of this study was to test the performance of both linear and nonlinear models
      to predict the skin permeation of a series of 11 compounds. METHODS: The
      modelling in this study was carried out by the application of both quantitative
      structure permeability relationships and Gaussian process-based machine learning
      methods to predict the flux and permeability coefficient of the 11 compounds. The
      actual permeation of these compounds across human skin was measured using Franz
      cells and a standard protocol with high performance liquid chromatography
      analysis. Statistical comparison between the predicted and experimentally-derived
      values was performed using mean squared error and the Pearson sample correlation
      coefficient. KEY FINDINGS: The findings of this study would suggest that the
      models failed to accurately predict permeation and in some cases were not within
      two- or three-orders of magnitude of the experimentally-derived values. However,
      with this set of compounds the models were able to effectively rank the
      permeants. CONCLUSIONS: Although not suitable for accurately predicting
      permeation the models may be suitable for determining a rank order of permeation,
      which may help to select candidate molecules for in-vitro screening. However, it
      is important to note that such predictions need to take into account actual
      relative drug candidate potencies.

PMID- 22420663
TI  - Anti-depressant effects of Xiaoyaosan on rat model of chronic unpredictable mild
      stress: a plasma metabonomics study based on NMR spectroscopy.
AB  - OBJECTIVES: To investigate the antidepressant effects of Xiaoyaosan (XYS) in a
      chronic unpredictable mild stress (CUMS) depression model. METHODS: The changes
      in behaviour and plasma metabolic profiles were investigated after four-week CUMS
      exposure and treatment. Drugs were administered during the four-week period of
      CUMS, with the healthy group serving as negative controls, and the fluoxetine and
      venlafaxine groups serving as positive controls. Plasma samples were collected at
      28th day, and the plasma metabolic profiling was measured using NMR, followed by
      multivariate analysis. KEY FINDINGS: Exposure to CUMS for four weeks caused
      depression-like behaviour in rats, as indicated by significant decreases in
      weight gain, sucrose consumption and locomotor activity. Eleven potential
      biomarkers, including seven in the Carr-Purcell-Meiboom-Gill spectra, five in the
      diffusion-edited spectra, and one in both were identified. It was found that
      trimethylamine-N-oxide, alanine, beta-hydroxybutyrate, valine,
      leucine/isoleucine, low-density lipoprotein/very low-density lipoprotein and
      lipids were lower and phosphatidylcholine, high-density lipoprotein, choline and
      N-acetyl glycoproteins were higher in CUMS-treated rats, as compared with
      controls. XYS significantly suppressed behavioural changes and attenuated plasma
      metabolite changes. CONCLUSIONS: XYS produced an obvious antidepressant effect,
      and the metabonomic approach benefits estimation of the pharmacodynamic action of
      traditional Chinese medicine prescriptions.

PMID- 22420664
TI  - PPARgamma agonist pioglitazone improves scopolamine-induced memory impairment in
      mice.
AB  - OBJECTIVES: This study was conducted to evaluate the effects of exposure to
      pioglitazone, a peroxisome proliferator-activated receptor agonist, on cognitive
      impairment induced by scopolamine, a muscarinic antagonist, in mice. METHODS:
      Pioglitazone (9mg/kg, 18mg/kg) was orally administered for 9 days at 30min before
      intraperitoneal injection with scopolamine (0.8mg/kg, i.p.). Cognitive function
      was evaluated by the passive avoidance test and the Morris water maze test on the
      10th day after treatment. Changes in cholinergic system reactivity were also
      examined by measuring the acetylcholine, acetylcholinesterase and choline
      acetyltransferase in the hippocampus and cortex. KEY FINDINGS: Scopolamine
      injection induced impaired performance in the passive avoidance test and the
      water maze test and severe decrease of cholinergic system reactivity, as
      indicated by reduced acetylcholine levels, decreased choline acetyltransferase
      activity and increased acetylcholinesterase activity. Daily administration of
      pioglitazone significantly increased step-through latency in passive avoidance
      test, and significantly decreased the escape latency, and increased the time
      spent in the platform quadrant in the Morris water maze test. Pioglitazone also
      protected against scopolamine-induced cholinergic system deficit, including
      reduced acetylcholine levels, decreased choline acetyltransferase activity and
      increased acetylcholinesterase activity in the hippocampus or cortex.
      CONCLUSIONS:   Pioglitazone demonstrates a significant neuroprotective effect
      against scopolamine-induced cholinergic system deficit and cognitive impairment.

PMID- 22420665
TI  - Luteolin inhibited hydrogen peroxide-induced vascular smooth muscle cells
      proliferation and migration by suppressing the Src and Akt signalling pathways.
AB  - OBJECTIVES: Luteolin is a naturally occurring flavonoid found in many vegetables,
      fruits and medicinal plants. The migration and proliferation of vascular smooth
      muscle cells (VSMCs) are the critical pathological processes in various
      cardiovascular diseases, such as atherosclerosis. In this study, we investigated
      the effect of luteolin and its latent mechanism on the proliferation and
      migration of VSMCs stimulated by hydrogen peroxide (H(2) O(2) ). METHODS: VSMC
      proliferation and cell viability was assayed using the 3-(4,5-dimethylthiazol
      2yl)-2,5-diphenyltetrazolium bromide (MTT) method or by cell counting, and H(2)
      O(2) -elicited migration of VSMCs was measured using a transwell migration assay.
      The phosphorylation levels of Src, 3-phosphoinositide-dependent kinase 1 (PDK1)
      and Akt (protein kinase B) were analysed by immunoblotting. KEY FINDINGS: This
      study demonstrated that luteolin showed a particularly inhibitory effect on H(2)
      O(2) -elicited VSMC proliferation and migration. In previous research, we
      originally explored the function of luteolin in blocking H(2) O(2) -triggered Src
      and Akt signalling pathways. The activation of Src, PDK1, Akt (308), Akt (473) in
      the luteolin-treated group was significantly lower than that seen in the H(2)
      O(2) group. CONCLUSIONS: These findings strongly suggested that luteolin
      suppresses H(2) O(2) -directed migration and proliferation in VSMCs partially due
      to down-regulation of the Akt and Src signalling pathways, which are important
      participants in the processes of migration and proliferation of VSMCs.

PMID- 22420666
TI  - Comparison of the effects of marchantin C and fucoidan on sFlt-1 and angiogenesis
      in glioma microenvironment.
AB  - OBJECTIVES: This study aimed to examine the effects of marchantin C and fucoidan
      on angiogenesis induced by glioma cells and monocytes, and to elucidate the role
      of sFlt-1 in this process. METHODS: T98G glioma cells and THP1 monocytes were
      pretreated with marchantin C or fucoidan, respectively. Conditioned media were
      used for endothelial cell tube formation assay and detection of sFlt-1 by ELISA.
      Depletion of sFlt-1 was achieved by a neutralizing antibody to assess its role in
      the process. KEY FINDINGS: Marchantin C inhibited angiogenesis induced by T98G
      cells while fucoidan inhibited both T98G and THP1 cell-induced angiogenesis. In
      all three groups in which angiogenesis was inhibited, sFlt-1 level in the
      supernatants was elevated. Pretreatment of the conditioned media with sFlt-1
      antibody restored the inhibited angiogenesis to a certain degree. CONCLUSIONS:
      This study suggested for the first time that marchantin C and fucoidan could
      significantly inhibit angiogenesis induced by glioma cells or monocytes. Up
      regulation of sFlt-1 played an important role in this process.

PMID- 22420667
TI  - Clove and eugenol in noncytotoxic concentrations exert immunomodulatory/anti
      inflammatory action on cytokine production by murine macrophages.
AB  - OBJECTIVES: The extract and essential oil of clove (Syzygium aromaticum) are
      widely used because of their medicinal properties. Eugenol is the most important
      component of clove, showing several biological properties. Herein we have
      analysed the immunomodulatory/anti-inflammatory effect of clove and eugenol on
      cytokine production (interleukin (IL)-1beta, IL-6 and IL-10) in vitro. METHODS:
      Macrophages were incubated with clove or eugenol (5, 10, 25, 50 or 100ug/well)
      for 24h. Concentrations that inhibited the production of cytokines were used
      before or after incubation with lipopolysaccharide (LPS), to verify a preventive
      or therapeutic effect. Culture supernatants were harvested for measurement of
      cytokines by enzyme-linked immunosorbent assay. KEY FINDINGS: Clove (100ug/well)
      inhibited IL-1beta, IL-6 and IL-10 production and exerted an efficient action
      either before or after LPS challenge for all cytokines. Eugenol did not affect IL
      1beta production but inhibited IL-6 and IL-10 production. The action of eugenol
      (50 or 100ug/well) on IL-6 production prevented efficiently effects of LPS either
      before or after its addition, whereas on IL-10 production it counteracted
      significantly LPS action when added after LPS incubation. CONCLUSIONS: Clove
      exerted immunomodulatory/anti-inflammatory effects by inhibiting LPS action. A
      possible mechanism of action probably involved the suppression of the nuclear
      factor-kappaB pathway by eugenol, since it was the major compound found in clove
      extract.

PMID- 22420668
TI  - Diagnosis of invasive fungal infections using real-time PCR assay in paediatric
      acute leukaemia induction.
AB  - Invasive fungal infections (IFI) lead to morbidity and mortality in neutropenic
      patients and in allogenic stem cell transplantation. Serum-based fungal detection
      assays have limitation of specificity or sensitivity. Studies on fungal DNA
      detection using real-time PCR in childhood leukaemia are lacking. The aim of this
      study was to develop sensitive and specific diagnostic tools for IFI in
      paediatric acute leukaemia patients using real-time PCR. Of 100 randomised
      paediatric acute leukaemia patients receiving antifungal prophylaxis with
      voriconazole/amphotericin B, single peripheral whole blood sample in EDTA was
      used for Pan-AC real-time PCR assay (detects nine Candida and six Aspergillus
      species) in patients who failed prophylaxis due to proven, probable, possible or
      suspected fungal infections. PCR results were retrospectively correlated with
      clinical profile. Real-time PCR test was positive in 18/29 (62%) patients who
      failed prophylaxis. The only patient with proven IFI (mucormycosis), real-time
      PCR assay was negative. Real-time PCR was positive in 2/4 (50%) patients with
      possible and 16/24 (66.6%) suspected IFI and 5/10 (50%) patients with pneumonia.
      By applying method A/B, sensitivity and positive predictive value could not be
      commented due to unproven Aspergillus or Candida infections; specificity and
      negative predictive values (NPV) were 41% and 100% respectively; by method C
      (included episodes of possible IFI as true positive), sensitivity, specificity,
      PPV and NPV were 50%, 36%, 11% and 81% respectively. In those with suspected IFI,
      8/24 (33.3%) were PCR negative and unnecessarily received empirical antifungal
      therapy (EAFT). Real-time PCR is a practical, rapid, non-invasive screening test
      for excluding IFI in paediatric leukaemia. The high NPV makes real-time PCR a
      promising tool to use this prior to initiating EAFT in antibiotic-resistant
      febrile neutropenic patients; this would avoid toxicity, cost and hospitalisation
      for EAFT (ClinicalTrials.gov identifier:NCT00624143).

PMID- 22420669
TI  - Ion pairing and anion-driven aggregation of an ionic liquid in aqueous salt
      solutions.
AB  - A relevant question regarding ionic liquids is whether they exist in aqueous
      solution as totally dissociated ions or as ionic pairs, molecularly dispersed or
      forming part of aggregates. Several methods were employed here to evaluate these
      points by comparing the results of an ionic liquid, 1-ethyl-3-methylimidazolium
      tosylate ([emim][TOS]) with its model compound p-toluenesulfonic acid (pTSA).
      Conductivity measurements of [emim][TOS] and pTSA dissolved in deionized water
      support the existence of small amounts of aggregates for both compounds, with a
      larger extent in the first case. However, apparent molar volume measurements
      provide no clear evidence for aggregation in aqueous solution or in NaCl aqueous
      solutions. In contrast, the excimer emission and the absorption and excitation
      spectra prove the existence of aggregates of [emim][TOS] and pTSA anions in
      aqueous solution, with and without salt, giving in addition structural
      information about them. It was thus found that only [emim][TOS] forms ion pairs
      in deionized water, which dissociate in the presence of NaCl. J-aggregates of
      pTSA and [emim][TOS] anions, with slip angles that decrease with increasing
      concentration, were observed through the excitation spectra, and the roles of the
      anion and cation as well as the effect of the presence of NaCl were analyzed.
      Thanks to aggregation-induced emission enhancement, fluorescence is much more
      sensitive than conductivity or density measurements to detect aggregation.

PMID- 22420670
TI  - Impact of multiple types of childhood trauma exposure on risk of psychiatric
      comorbidity among alcoholic inpatients.
AB  - BACKGROUND: This study examined the prevalence of single- and multiple-type
      childhood trauma exposure (CTE) among alcoholic patients undergoing inpatient
      detoxification and treatment. The relationships between various types of CTE and
      lifetime psychiatric comorbidities and suicide attempts were also explored.
      METHODS: A total of 196 alcoholic inpatients were assessed by Structured Clinical
      Interview for DSM-IV Axis I Disorders and Childhood Trauma Questionnaire (CTQ)
      for CTE history. RESULTS: The overall prevalence of CTE in the entire sample was
      high (55.1%). Specifically, the prevalence of emotional abuse was 21.4%, physical
      abuse 31.1%, sexual abuse 24.0%, emotional neglect 20.4%, and physical neglect
      19.9%. Regarding multiple types of CTE, 31.7 and 18.9% reported at least 2 and at
      least 3 CTE types, respectively. Strikingly, among those with at least 1 positive
      CTQ category, more than half reported 2 or more CTE types. A history of emotional
      abuse increased the risk of mood disorder, in particular major depressive
      disorder, as well as posttraumatic stress disorder (PTSD). Physical abuse
      contributed to the prediction of suicide attempts, while sexual abuse was
      associated with a diagnosis of anxiety disorder, PTSD, and multiple comobidities
      (e.g., anxiety and mood disorder). The number of reported CTE types or the total
      score of the CTQ predicted an increased risk of having single or multiple
      psychiatric comorbidities as well as suicide attempts. CONCLUSIONS: We observed
      high rates of a broad range of CTE types and a trend for CTE-specific enhancement
      of risk for various psychiatric outcomes among alcoholic inpatients. Of note, a
      dose-response relationship between number of CTE types and risk of psychiatric
      comorbidities as well as suicide attempts was found. We suggest a wide range of
      CTE should be included when exploring the effects of CTE or developing prevention
      and treatment strategies among alcoholic subjects.

PMID- 22420671
TI  - Prevalence, course and impact of HLA donor-specific antibodies in liver
      transplantation in the first year.
AB  - The presence of preformed donor-specific HLA antibodies (DSA) in liver transplant
      recipients is increasingly recognized; however, the prevalence of DSA and their
      impact on early allograft function remains unknown. We prospectively followed
      serum DSA levels of 90 consecutive liver transplant recipients from baseline to 4
      months. Twenty recipients (22.2%) had preformed DSA. No antibody-targeting
      treatments were undertaken. Seven days after transplantation, DSA levels
      decreased markedly in all but three patients. Day 7 protocol biopsies showed
      diffuse C4d deposition along the portal stroma, central vein, subendothelial and
      stromal space in the patients with persistent high DSA levels. The rate of acute
      cellular rejection was not significantly different in patients with DSA. The
      transaminase and bilirubin levels remained comparable during the first year
      despite the presence of DSA. The three patients with persistently high DSA levels
      continue to have normal allograft function. We conclude that in most cases, DSA
      disappear after liver transplant, however in rare instances where they persist,
      there is evidence of complement activation in the liver allograft, without
      significant clinical impact in the first year.

PMID- 22420672
TI  - Online monitoring of molecular processes in a plasma air purifying system.
AB  - Plasma air purifying systems present an interesting alternative to filters for
      purifying air. In this study, molecular processes in a commercially available ac
      driven plasma air purifier were studied in detail. This air purifier is supposed
      to reduce all air contaminants to small nontoxic molecules (e.g., H(2)O and
      CO(2)). However, degradation mechanisms are not yet fully understood. In this
      study, we investigated the exhaust of the plasma air purifier to determine which
      degradation products are formed. An interface was designed and constructed to
      allow the direct coupling of the plasma air purifier's exhaust to a mass
      spectrometer. The compounds studied, primary and secondary amines, were
      introduced at a concentration of 1 ppmV. Contrary to our expectations,
      polymerization instead of degradation was observed. The higher the ac voltage
      applied (max. 9.0 kV) to the plasma air purifier, the higher the mass of the
      oligomer distribution. Side chain oxidation products as well as oligomers could
      be observed for all compounds tested. Starting with amines of low mass (m/z <
      200), compounds of molecular masses above 1000 Da were observed in the plasma air
      purifier. Detailed analysis of the observed mass spectra as well as experiments
      with deuterated dibutylamine helped to unravel the mechanism taking place in the
      plasma air purifier. Nitrate anions generated in the plasma air purifier
      (presumably from N(2)) are proposed to form ionic clusters with protonated
      amines.

PMID- 22420673
TI  - HIV research.

PMID- 22420674
TI  - HIV risk, partner violence, and relationship power among Filipino young women:
      testing a structural model.
AB  - A person's ability to minimize HIV risk is embedded in a complex,
      multidimensional context. In this study, we tested a model of how relationship
      power impacts IPV victimization, which in turn impacts HIV risk behaviors. We
      analyzed data from 474 young adult women (aged 15-31) in Cebu Province,
      Philippines, using structural equation modeling, and demonstrated good fit for
      the models. High relationship power is directly associated with increased IPV
      victimization, and IPV victimization is positively associated with increased HIV
      risk. We highlight in this article the complex dynamics to consider in HIV risk
      prevention among these young women.

PMID- 22420675
TI  - Mano a Mano-Mujer: an effective HIV prevention intervention for Chilean women.
AB  - The impact of a professionally facilitated peer group intervention for HIV
      prevention among 400 low-income Chilean women was examined using a
      quasiexperimental design. At 3 months postintervention, the intervention group
      had higher HIV-related knowledge, more positive attitudes toward people living
      with HIV, fewer perceived condom use barriers, greater self- efficacy, higher HIV
      reduction behavioral intentions, more communication with partners about safer
      sex, and decreased depression symptoms. They did not, however, have increased
      condom use or self-esteem. More attention to gender barriers is needed. This
      intervention offers a model for reducing HIV for women in Chile and other Latin
      American countries.

PMID- 22420676
TI  - Fertility intent and contraceptive decision-making among HIV positive and
      negative antenatal clinic attendees in Durban, South Africa.
AB  - We explored contraceptive decision-making among South African antenatal clinic
      attendees, fertility intent post-HIV diagnosis, and women's experiences at
      government health facilities. Data are from in-depth interviews with HIV negative
      and HIV positive women. We interviewed women in Zulu; interviews were recorded,
      transcribed, and translated. We conducted qualitative analyses of interviews.
      Women were the dominant decisionmakers about contraceptive use, whether they
      involved their partners or not. A majority of women obtained a contraceptive
      method at a government facility; however, several women were unable to attain
      sterilizations. Women were presented with limited contraceptive options and were
      not always able to access services.

PMID- 22420677
TI  - Ugandan men's attitudes toward their partner's participation in antenatal HIV
      testing.
AB  - Several authors have shown that women's uptake of antenatal HIV testing is
      influenced by fear of their partners' reactions. We conducted a qualitative study
      with 40 Ugandan men to examine their attitudes toward their partners'
      participation in antenatal HIV testing. Most men believed women should consult
      their husbands prior to HIV testing to avoid negative consequences and facilitate
      disclosure. When women tested during routine antenatal care, however, the need to
      obtain permission was considered less important. These findings lend support to
      the practice of routine antenatal HIV testing as an acceptable way for women to
      test independently of their partners.

PMID- 22420678
TI  - Depression in HIV-positive women in Gaborone, Botswana.
AB  - This cross-sectional study measured prevalence of depression and suicide ideation
      in 62 randomly selected HIV-positive (HIV+) women in Botswana, a resource-limited
      country at the center of the HIV/AIDS epidemic. They were administered two
      screening measures of depression, an inventory of activities of daily living
      (ADL), and subjective questionnaire of cognitive functioning. Results show that
      the two screening measures are useful for detecting depression in women infected
      with HIV in resource-limited countries. Diagnosis of depression is of great
      importance, not only clinically, but also to ensure judicious allocation of
      scarce medical resources in the regions worst affected by the HIV epidemic.

PMID- 22420679
TI  - HIV-positive mothers with late adolescent/early adult children: "empty nest"
      concerns.
AB  - In-depth interviews about the "empty nest" were conducted with 57 HIV-positive
      mothers of late adolescent/early adult children. Empty nest worries included the
      following: (a) identity loss, (b) loss of social support, (c) financial
      insecurity, (d) worsening of physical health, and (e) death/dying. Hopes included
      the following: (a) self-improvement, (a) change of life focus, (c) travel, (d)
      romantic partners, and (e) familial ties. Respondents' HIV/AIDS status colored
      their thoughts/feelings about the empty nest; some worries were specific to being
      HIV positive and would not occur for nonill mothers. Midlife HIV-positive women
      need health care/social service resources as they navigate health and social
      psychological challenges to successful aging.

PMID- 22420680
TI  - HIV-infected women's relationships with their health care providers in the rural
      deep south: an exploratory study.
AB  - Through this qualitative study we explored the patient/provider relationships of
      rural HIV-infected women. Thirty-nine women from rural Alabama were recruited to
      participate in one of four focus groups. The focus groups were audiorecorded, and
      the participants were asked to complete surveys measuring patient/provider trust.
      The verbatim-transcribed audio recordings were analyzed using content analysis.
      The participants' descriptions of their relationships with health care providers
      were represented by three major thematic categories: caring, informative, and
      competent. These findings provide a foundation for further research on the role
      of patient/provider relationships in the health outcomes of HIV disease in rural,
      resource-poor settings.

PMID- 22420681
TI  - Oscillatory forces of nanoparticle suspensions confined between rough surfaces
      modified with polyelectrolytes via the layer-by-layer technique.
AB  - This paper addresses the systematic study of surface roughness effects on the
      internal structuring of silica nanoparticle suspensions under confinement. The
      confining surfaces are modified by physisorption of layers of oppositely charged
      polyelectrolytes with the so-called layer-by-layer technique. The layer-by-layer
      technique modifies the surface roughness without changing the surface potential
      of a multilayer with the same outermost layer, by increasing the number of
      constituent layers and ionic strength of the polyelectrolyte solutions and by
      selecting an appropriate pair of polyelectrolytes. The oscillatory forces of
      nanoparticle suspensions with a particle diameter of 26 nm are measured by a
      colloidal-probe atomic force microscope (CP-AFM). The characteristic lengths of
      the oscillatory force, i.e., wavelength, which indicates interparticle distance,
      and decay length, or particle correlation length, are not affected by the surface
      roughness. The corresponding reduction in the oscillatory amplitude and the shift
      in the phase correlate with an increase in surface roughness. Increasing surface
      roughness further induces a disappearance of the oscillations, and both confining
      surfaces contribute to the effect of surface roughness on the force reduction. In
      order to show an oscillatory force, the particles have to show positional
      correlation over a reasonably long range perpendicular to the surface, and the
      correlation function should be the same over a larger lateral area. This requires
      that both the particles and the surfaces have a high degree of order or symmetry;
      otherwise, the oscillation does not occur. A roughness of a few nanometers on a
      single surface, which corresponds to about 10% of the nanoparticle diameter, is
      sufficient to eliminate the oscillatory force.

PMID- 22420682
TI  - The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine.
AB  - BACKGROUND: Although caffeine supplementation improves performance, the ergogenic
      effect is variable. The cause(s) of this variability are unknown. A (C/A) single
      nucleotide polymorphism at intron 1 of the cytochrome P450 (CYP1A2) gene
      influences caffeine metabolism and clinical outcomes from caffeine ingestion. The
      purpose of this study was to determine if this polymorphism influences the
      ergogenic effect of caffeine supplementation. METHODS: Thirty-five trained male
      cyclists (age = 25.0 +/- 7.3 yrs, height = 178.2 +/- 8.8 cm, weight = 74.3 +/-
      8.8 kg, VO2max = 59.35 +/- 9.72 ml.kg-1.min-1) participated in two computer
      simulated 40-kilometer time trials on a cycle ergometer. Each test was performed
      one hour following ingestion of 6 mg.kg-1 of anhydrous caffeine or a placebo
      administered in double-blind fashion. DNA was obtained from whole blood samples
      and genotyped using restriction fragment length polymorphism-polymerase chain
      reaction. Participants were classified as AA homozygotes (N = 16) or C allele
      carriers (N = 19). The effects of treatment (caffeine, placebo) and the treatment
      * genotype interaction were assessed using Repeated Measures Analysis of
      Variance. RESULTS: Caffeine supplementation reduced 40 kilometer time by a
      greater (p < 0.05) magnitude in AA homozygotes (4.9%; caffeine = 72.4 +/- 4.2
      min, placebo = 76.1 +/- 5.8 min) as compared to C allele carriers (1.8%; caffeine
      = 70.9 +/- 4.3 min, placebo = 72.2 +/- 4.2 min). CONCLUSIONS: Results suggest
      that individuals homozygous for the A allele of this polymorphism may have a
      larger ergogenic effect following caffeine ingestion.

PMID- 22420683
TI  - Acute pulmonary oedema in pregnant women.
AB  - Acute pulmonary oedema in pregnant women is an uncommon but life-threatening
      event. The aims of this review are to address why pulmonary oedema occurs in
      pregnant women and to discuss immediate management. We performed a systematic
      literature search of electronic databases including MEDLINE, EMBASE and the
      Cochrane Library, using the key words obstetrics, pregnancy, acute pulmonary
      oedema, pregnancy complications, maternal, cardiac function and haemodynamics. We
      present a simple clinical classification of acute pulmonary oedema in pregnancy
      into pulmonary oedema occurring in normotensive or hypotensive women (i.e.
      without hypertension), and acute pulmonary oedema occurring in hypertensive
      women, which allows focused management. Pre-eclampsia remains an important cause
      of hypertensive acute pulmonary oedema in pregnancy and preventive strategies
      include close clinical monitoring and restricted fluid administration. Immediate
      management of acute pulmonary oedema includes oxygenation, ventilation and
      circulation control with venodilators. Pregnancy-specific issues include
      consideration of the physiological changes of pregnancy, the risk of aspiration
      and difficult airway, reduced respiratory and metabolic reserve, avoidance of
      aortocaval compression and delivery of the fetus.

PMID- 22420684
TI  - Non-exposed bisphosphonate-related osteonecrosis of the jaw: a critical
      assessment of current definition, staging, and treatment guidelines.
AB  - Non-exposed bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a newly
      reported complication arising from bisphosphonate therapy that presents with
      atypical symptoms and no apparent mucosal fenestration or exposure of necrotic
      bone. The clinical observation of the presence of necrotic bone underneath normal
      epithelial coverage was not conclusive for the diagnosis of BRONJ based on
      current guidelines established by the American Association of Oral and
      Maxillofacial Surgeons (AAOMS) and the American Society for Bone and Mineral
      Research (ASBMR), which specify the presence of clinically exposed necrotic bone
      for more than 8 weeks. Hence, the purpose of this review is to critically assess
      the current guidelines for diagnosis and management of BRONJ and propose a
      modified staging system and treatment guidelines to properly address the non
      exposed variant of BRONJ lesions.

PMID- 22420685
TI  - Working with interpreters in cross-cultural qualitative research in the context
      of a developing country: systematic literature review.
AB  - AIMS: This article is a report of a systematic literature review describing how
      cross-cultural researchers conducted qualitative studies with interpreters in
      Tanzania. The purpose was to draw methodological implications for working with
      interpreters within the context of developing countries. BACKGROUND: In a growing
      number of cross-cultural nursing studies in developing countries, interpreters
      play a crucial role for imparting verbal and cultural understanding. In many
      studies, however, the interpreters' role and their influences on the findings are
      not adequately described, and therefore the study credibility is weakened. DATA
      SOURCES: Cross-cultural qualitative studies conducted with interpreters in
      Tanzania were searched in four databases. Meeting our inclusion criteria were 20
      studies published from 1994-2009. REVIEW METHODS: We used Garrard's Matrix Method
      following Wallin and Ahlstrom's framework to analyse how cross-cultural
      researchers described the role of interpreters. RESULTS: We identified three
      major patterns of how researchers worked with interpreters: (i) invisible
      assistance, (ii) independent fieldwork and (iii) integrated collaboration. In
      many studies, interpreters' information was limited. They were often asked to
      collect data in the field without the presence of the researcher. They were
      integrated into the research process beyond data collection, such as subject
      recruitment, review of interviews, transcription and translation and analysis.
      CONCLUSION: From planning of research to dissemination of the findings, nurse
      researchers should carefully consider interpreters' influences on the findings.
      They may use a set of questions we developed for working with interpreters in
      developing countries to systematically describe the interpreter's role and
      maximize their research credibility.

PMID- 22420686
TI  - Introduction of glyco, peptido, carboxy, and alkyno substituents at the
      calixarene exo rim via the p-bromodienone route.
AB  - The conceptually novel "p-bromodienone route", which allows the direct
      introduction of nucleophiles at the calixarene exo rim, has been extended to
      anionic C-nucleophiles (acetylides) to give chiral meta-substituted
      alkynocalix[4]arenes and to appropriate O-nucleophiles to obtain para-substituted
      glyco, peptido, and carboxy derivatives.

PMID- 22420687
TI  - The in vivo dynamic organization of BRCA1-A complex proteins at DNA damage
      induced nuclear foci.
AB  - The breast cancer associated gene 1 (BRCA1)-A protein complex assembles at DNA
      damage-induced nuclear foci to facilitate repair of double-stranded breaks. Here,
      we describe the first systematic comparison of the dynamics, copy number and
      organization of its core components at foci. We show that the protein pools at
      individual foci generally comprise a small immobile fraction (~20%) and larger
      mobile fraction (~80%), which together occupy the same focal space but exist at
      different densities. In the mobile fraction, Abraxas (CCDC98) and the heterodimer
      BARD1-BRCA1 share similar rates of dynamic exchange (complete turnover in ~500
      seconds). In contrast, RAP80, which is required for initial foci assembly, was
      more dynamic with 25-fold faster turnover at mature foci. In addition, Abraxas,
      BARD1, BRCA1 and Merit40 (NBA1) were stably retained in the immobile fraction of
      foci under conditions causing loss of BRCC36 and RAP80, suggesting a shift to
      RAP80-independent localization after foci formation. These results, combined with
      our finding that RAP80 (~1200 copies per focus) is twofold more abundant than
      Abraxas/BARD1/BRCA1 at foci, suggest new models defining the dynamic organization
      of BRCA1-A complex at mature foci, wherein the unusually fast turnover of RAP80
      may contribute to its regulation of BRCA1-dependent DNA repair.

PMID- 22420688
TI  - The pulse spectrum analysis at three stages of pregnancy.
AB  - OBJECTIVES: This study is the first to detect the radial pulses of the three
      diagnosis positions (inch, bar, and cubit) in both wrists (six positions) by
      pulse spectrum analysis. The purpose of this study was to identify the difference
      among pulses of the six positions at three stages of pregnancy and to examine
      whether the results of this study agree with the theory of Traditional Chinese
      Medicine (TCM), which states that the cubit pulse shows unique changes for an
      expectant woman and that the pulse changes coincide with the progression of
      gestation. SUBJECTS AND METHODS: One hundred and fifty (150) healthy pregnant
      women were divided into three groups according to gestational age (9-14 weeks, 20
      28 weeks, and 32-37 weeks of gestation) and 50 healthy nonpregnant women were
      used as controls. A pulse analyzer was used to detect the six positions of the
      radial pulses and to calculate the 10 relative energy values of the spectrum's
      harmonics of the six positions. RESULTS: Results show that most of the 10
      relative spectral energy values of the right and left cubits are statistically
      (p<0.01) higher than those of the inch for the pregnant women as compared with
      the nonpregnant women. In addition, the 10 relative spectral energy values of the
      six positions are not identical at the three stages of pregnancy. CONCLUSIONS:
      The cubit pulse is unique for pregnant women, which is consistent with the theory
      of TCM. In addition, the pulse conditions at the three stages of pregnancy are
      dissimilar.

PMID- 22420689
TI  - Pd nanowires as new biosensing materials for magnified fluorescent detection of
      nucleic acid.
AB  - The designed synthesis of new nanomaterials with controlled shape, composition,
      and structure is critical for tuning their physical and chemical properties, and
      further developing interesting analytical sensing devices. Herein, we presented
      that Pd nanowires (NWs) can be used as a new biosensing platform for high
      sensitivity nucleic acid detection. The general sensing concept is based on the
      fact that Pd NWs can adsorb the fluorescently labeled single-stranded DNA probe
      and lead to substantial fluorescence quenching of dye, followed by specific
      hybridization with the complementary region of the target DNA sequence. This
      results in desorption of double-stranded DNA from Pd NWs surface and subsequent
      recovery of fluorescence. Furthermore, an amplification strategy based on Pd NWs
      for nucleic acid detection by using exonuclease III (Exo III) was demonstrated.
      The present dual-magnification sensing system combined Pd NWs with Exo III has a
      detection range of 1.0 nM to 2.0 MUM with the detection limit of 0.3 nM (S/N =
      3), which is about 20-fold higher than that of traditional unamplified
      homogeneous assays.

PMID- 22420690
TI  - Learning from positive and negative monetary feedback in patients with alcohol
      dependence.
AB  - BACKGROUND: Chronic and excessive consumption of alcohol is associated with
      structural, physiological, and functional changes in multiple regions of the
      human brain including the prefrontal cortex, the medial temporal lobe, and the
      structures of the reward system. The present study aimed to assess the ability of
      alcohol-dependent patients (ADP) to learn probabilistic stimulus-reward
      contingencies and to transfer the acquired knowledge to new contexts. During
      transfer, the relative preference to learn from positive or negative feedback was
      also assessed. METHODS: Twenty-four recently detoxified ADP and 20 healthy
      controls engaged in a feedback learning task with monetary rewards. The learning
      performance per se and transfer performance including positive versus negative
      learning were examined, as well as the relationship between different learning
      variables and variables comprising alcohol and nicotine consumption patterns,
      depression, and personality traits (harm avoidance and impulsivity). RESULTS:
      Patients did not show a significant general learning deficit in the acquisition
      of stimulus-response-outcome associations. Fifteen healthy subjects and 13
      patients reached the transfer phase, in which ADP showed generally lower
      performance than healthy controls. There was no specific deficit with regard to
      learning from positive or negative feedback. The only near-significant (negative)
      correlation between learning variables and drug consumption patterns, depression,
      and personality traits emerged for harm avoidance and positive learning in
      controls. CONCLUSIONS: Impaired transfer performance suggests that ADP had
      problems applying their acquired knowledge in a new context. Potential relations
      to dysfunctions of specific brain structures and implications of the finding for
      therapy are discussed.

PMID- 22420691
TI  - Molecular dynamics simulation of PEGylated bilayer interacting with salt ions: a
      model of the liposome surface in the bloodstream.
AB  - PEGylation is an effective mechanism to prolong the bloodstream lifetime, and
      thus efficacy, of drug delivery liposomes. The mechanism through which
      poly(ethylene glycol) (PEG) increases bloodstream lifetime is, however, not
      completely understood. The interaction with salt ions found in the bloodstream is
      known to play a role in this. We have used all-atom molecular dynamics simulation
      to study the effect of PEGylated lipid density, salt concentration, and the
      interaction with KCl and CaCl(2) salts in addition to NaCl. Increasing the
      PEGylated lipid concentration in the formulation from 1:18 to 1:9 molar density
      decreased the extent to which the Cl(-) ions penetrated the PEG layer, thus
      causing the PEG layer to become effectively positively charged. The interaction
      of the PEG with the K(+) ions was weaker than for the Na(+) ions, and nonexistent
      for the Ca(2+) ions. This work expands on our previous work where we studied the
      gel and liquid crystalline membranes in physiological salt concentration. Our
      results provide both an explanation for the experimental observation that
      PEGylation inhibits calcium-induced liposome fusion and further insight into the
      mechanisms through which PEG may inhibit uptake of the liposome by the
      reticuloendothilial system (RES).

PMID- 22420692
TI  - Tolerance to environmental desiccation in moss sperm.
AB  - * Sexual reproduction in mosses requires that sperm be released freely into the
      environment before finding and fertilizing a receptive female. After release from
      the male plant, moss sperm may experience a range of abiotic stresses; however,
      few data are available examining stress tolerance of moss sperm and whether there
      is genetic variation for stress tolerance in this important life stage. * Here,
      we investigated the effects of environmental desiccation and recovery on the
      sperm cells of three moss species (Bryum argenteum, Campylopus introflexus, and
      Ceratodon purpureus). * We found that a fraction of sperm cells were tolerant to
      environmental desiccation for extended periods (d) and that tolerance did not
      vary among species. We found that this tolerance occurs irrespective of ambient
      dehydration conditions, and that the addition of sucrose during dry-down improved
      cell recovery. Although we observed no interspecific variation, significant
      variation among individuals within species in sperm cell tolerance to
      environmental desiccation was observed, suggesting selection could potentially
      act on this basic reproductive trait. * The observation of desiccation-tolerant
      sperm in multiple moss species has important implications for understanding
      bryophyte reproduction, suggesting the presence of a significant, uncharacterized
      complexity in the ecology of moss mating systems.

PMID- 22420693
TI  - Ideal and actual involvement of community pharmacists in health promotion and
      prevention: a cross-sectional study in Quebec, Canada.
AB  - BACKGROUND: An increased interest is observed in broadening community
      pharmacists' role in public health. To date, little information has been gathered
      in Canada on community pharmacists' perceptions of their role in health promotion
      and prevention; however, such data are essential to the development of public
      health programs in community pharmacy. A cross-sectional study was therefore
      conducted to explore the perceptions of community pharmacists in urban and semi
      urban areas regarding their ideal and actual levels of involvement in providing
      health-promotion and prevention services and the barriers to such involvement.
      METHODS: Using a five-step modified Dillman's tailored design method, a
      questionnaire with 28 multiple-choice or open-ended questions (11 pages plus a
      cover letter) was mailed to a random sample of 1,250 pharmacists out of 1,887
      community pharmacists practicing in Montreal (Quebec, Canada) and surrounding
      areas. It included questions on pharmacists' ideal level of involvement in
      providing health-promotion and preventive services; which services were actually
      offered in their pharmacy, the employees involved, the frequency, and duration of
      the services; the barriers to the provision of these services in community
      pharmacy; their opinion regarding the most appropriate health professionals to
      provide them; and the characteristics of pharmacists, pharmacies and their
      clientele. RESULTS: In all, 571 out of 1,234 (46.3%) eligible community
      pharmacists completed and returned the questionnaire. Most believed they should
      be very involved in health promotion and prevention, particularly in smoking
      cessation (84.3%); screening for hypertension (81.8%), diabetes (76.0%) and
      dyslipidemia (56.9%); and sexual health (61.7% to 89.1%); however, fewer
      respondents reported actually being very involved in providing such services
      (5.7% [lifestyle, including smoking cessation], 44.5%, 34.8%, 6.5% and 19.3%,
      respectively). The main barriers to the provision of these services in current
      practice were lack of: time (86.1%), coordination with other health care
      professionals (61.1%), staff or resources (57.2%), financial compensation
      (50.8%), and clinical tools (45.5%). CONCLUSIONS: Although community pharmacists
      think they should play a significant role in health promotion and prevention,
      they recognize a wide gap between their ideal and actual levels of involvement.
      The efficient integration of primary-care pharmacists and pharmacies into public
      health cannot be envisioned without addressing important organizational barriers.

PMID- 22420694
TI  - Reprint of: the paradox of alpha-adrenergic coronary vasoconstriction revisited.
AB  - Activation of coronary vascular alpha-adrenoceptors results in vasoconstriction
      which competes with metabolic vasodilation during sympathetic activation.
      Epicardial conduit vessel constriction is largely mediated by alpha(1)
      adrenoceptors; the constriction of the resistive microcirculation largely by
      alpha(2)-adrenoceptors, but also by alpha(1)-adrenoceptors. There is no firm
      evidence that alpha-adrenergic coronary vasoconstriction exerts a beneficial
      effect on transmural blood flow distribution. In fact, alpha-blockade in
      anesthetized and conscious dogs improves blood flow to all transmural layers,
      during normoperfusion and hypoperfusion. Also, in patients with coronary artery
      disease, blockade of alpha(1)- and alpha(2)-adrenoceptors improves coronary blood
      flow, myocardial function and metabolism. This article is part of a Special Issue
      entitled "Coronary Blood Flow".

PMID- 22420695
TI  - Individual, interpersonal, and institutional level factors associated with the
      mental health of college students.
AB  - OBJECTIVE: This study investigates the individual, interpersonal, and
      institutional level factors that are associated with overall mental health among
      college students. PARTICIPANTS: Data are from an online cross-sectional survey of
      2,203 students currently enrolled at a large public university. METHODS: Mental
      health was ascertained using a subcomponent of the RAND Medical Outcomes Study
      functioning and well-being measures developed by the RAND corporation. Stepwise
      regression was used to determine if self-reported measures of individual (ie,
      coping abilities), interpersonal (ie, intergroup awareness), and institutional
      (ie, campus climate/tension) level factors were associated with overall mental
      health, after controlling for demographic characteristics. RESULTS: The combined
      effects of both individual and institutional level measures were associated with
      student mental health. In particular, limited coping abilities and a perceived
      racially tense campus climate contributed to the psychological distress of
      college students. CONCLUSIONS: Simultaneously addressing the individual and
      institutional level influences on mental health offers the most promising help
      for students.

PMID- 22420696
TI  - Use of and interest in smoking cessation strategies among daily and nondaily
      college student smokers.
AB  - OBJECTIVE: To examine use of and interest in cessation strategies among nondaily
      and daily college student smokers. PARTICIPANTS: 800 undergraduate student
      smokers aged 18 to 25. METHODS: The authors examined nondaily versus daily
      smoking in relation to use of and interest in cessation strategies using an
      online survey. RESULTS: Nondaily (65.8%) versus daily smokers (34.3%) were more
      likely to have made a quit attempt (p = .01) but less likely to have used any
      assistance (p < .001). Nondaily smokers were less interested in pharmacotherapy
      and traditional behavioral interventions; however, there was no difference in
      interest in technology-based interventions among nondaily versus daily smokers.
      Controlling for covariates, there were no significant differences in interest in
      traditional or technology-based behavioral interventions. Higher motivation,
      lower confidence, and depressive symptomatology were related to interest in each
      intervention. Smoking for social reasons was related to interest in technology
      based interventions. CONCLUSIONS: Different intervention strategies may be
      appropriate for nondaily and daily smokers.

PMID- 22420697
TI  - A qualitative analysis of college women's leaving processes in abusive
      relationships.
AB  - OBJECTIVE: This study assessed the process of leaving an abusive dating
      relationship utilizing a qualitative design. METHODS: Participants included 123
      college women in abusive dating relationships who participated at the beginning
      and end of a 10-week academic quarter. RESULTS: Qualitative content analyses were
      used to analyze the transcribed responses to an open-ended question about women's
      leaving processes over the interim period. A variety of categories and themes
      emerged for women in different stages of the leaving process, consistent with the
      Transtheoretical Model of Change and Investment Model. Data also underscored
      women's lack of acknowledgment, minimization, and normalization of abuse.
      CONCLUSIONS: These data demonstrate the importance of dating violence
      intervention and prevention programming on college campuses and offer information
      that may be useful to college health providers who assist women in abusive dating
      relationships.

PMID- 22420698
TI  - Enhancing women's resistance to sexual coercion: a randomized controlled trial of
      the DATE program.
AB  - OBJECTIVE: Despite extensive efforts to develop sexual assault prevention
      programs for college women, few have been rigorously evaluated, and fewer have
      demonstrable effects on victimization. This study pilots the Dating Assertiveness
      Training Experience (DATE), designed to train young women in assertiveness skills
      for responding to sexual coercion and to provide them opportunities to practice
      these skills in a safe environment. PARTICIPANTS: One hundred thirty-nine female
      college students from a private university in the Southwest. METHODS:
      Participants were randomly assigned to DATE or a no-treatment control group.
      Sexual victimization and response to acts of sexual aggression were assessed
      prior to randomization, after intervention, and monthly for 3 months. RESULTS:
      Women who completed DATE were less likely to be victimized than women in the
      control condition; those who were victimized were more likely to respond
      assertively. CONCLUSIONS: Assertiveness training for resisting sexual coercion
      holds promise for reducing sexual victimization of young women.

PMID- 22420699
TI  - Psychological distress and related factors in female college students.
AB  - OBJECTIVE: This study assessed the psychological distress in Spanish college
      women and analyzed it in relation to sociodemographic and academic factors.
      PARTICIPANTS AND METHODS: The authors selected a stratified random sampling of
      1,043 college women (average age of 22.2 years). Sociodemographic and academic
      information were collected, and psychological distress was assessed with the
      Symptom Checklist-90-Revised. RESULTS: This sample of college women scored the
      highest on the depression dimension and the lowest on the phobic anxiety
      dimension. The sample scored higher than women of the general population on the
      dimensions of obsessive-compulsive, interpersonal sensitivity, paranoid ideation,
      psychoticism, and on the Global Severity Index. Scores in the sample
      significantly differed based on age, relationship status, financial independence,
      year of study, and area of study. CONCLUSION: The results indicated an elevated
      level of psychological distress among college women, and therefore college health
      services need to devote more attention to their mental health.

PMID- 22420700
TI  - Nonmedical use of prescription stimulants during college: four-year trends in
      exposure opportunity, use, motives, and sources.
AB  - OBJECTIVE: Examine trends in nonmedical use of prescription stimulants (NPS),
      including motives, routes of administration, sources, cost, and risk factors.
      PARTICIPANTS: 1,253 college students. METHODS: Data were collected annually
      during academic years 2004-2005 through 2008-2009. Generalized estimating
      equations analyses evaluated longitudinal trends. Logistic regression models
      evaluated stability of associations between risk factors and NPS over time.
      RESULTS: Almost two-thirds (61.8%(wt)) were offered prescription stimulants for
      nonmedical use by Year 4, and 31.0%(wt) used. Studying was the predominant motive
      (73.8% to 91.5% annually), intranasal administration was modest (< 17% annually),
      and the most common source was a friend with a prescription (>= 73.9% annually).
      Significant changes over time included decreasing curiosity motives, increasing
      overuse of one's own prescription, and increasing proportion paying $5+ per pill.
      Lower grade point average and alcohol/cannabis use disorders were consistently
      associated with NPS, holding constant other factors. CONCLUSIONS: Prevention
      opportunities exist for parents, physicians, and college administrators to reduce
      NPS.

PMID- 22420701
TI  - Drunkorexia: understanding the co-occurrence of alcohol consumption and
      eating/exercise weight management behaviors.
AB  - OBJECTIVE: Examine the co-occurrence of alcohol consumption, physical activity,
      and disordered eating behaviors via a drunkorexia perspective. PARTICIPANTS:
      Nationally representative sample (n = 22,488) of college students completing the
      Fall 2008 National College Health Assessment. METHODS: Hierarchical logistic
      regression was employed to determine if physical activity and disordered eating
      behaviors uniquely predicted binge drinking, while controlling for age, race,
      gender, year in college, Greek membership, and place of residence. RESULTS:
      Physical activity and disordered eating made unique, statistically significant
      contributions. Moreover, including physical activity and disordered eating
      behaviors allowed for the correct classification of an additional 431 cases (ie,
      binge drinkers) over and above the predictive ability of the covariate-only
      model. CONCLUSIONS: Findings corroborate prior research indicating highly active
      college students are more likely to binge drink than their nonactive peers, and
      highlight the potential of a drunkorexia perspective in explaining the
      counterintuitive alcohol-activity association among college students.

PMID- 22420702
TI  - Waterpipe smoking among college students in the United States: a review of the
      literature.
AB  - OBJECTIVE: To review the literature on college student waterpipe use with a focus
      on undergraduates in the United States. PARTICIPANTS: Undergraduate students.
      METHODS: Studies were accessed using the databases PubMed, MEDLINE, PsycINFO, and
      Academic Search Premier. Searches included combinations of the following
      keywords: "waterpipe," "hookah," "shisha," "nargila," "argileh," "hubble bubble,"
      "college," "university," and "student." RESULTS: Results demonstrate that
      approximately 1 in 5 American college students report past-year waterpipe use.
      Results also suggest that there are a number of established correlates of
      waterpipe smoking, including male gender, Arab ethnicity, cigarette smoking, and
      the belief that waterpipe smoking is less harmful than cigarette smoking.
      CONCLUSIONS: Despite its harmful health effects, waterpipe smoking is quite
      common among college students. Future research with better methodologies and
      theoretical frameworks are needed to advance the field.

PMID- 22420703
TI  - Improving understanding about tanning behaviors in college students: a pilot
      study.
AB  - OBJECTIVE: Melanoma is the second most common cancer diagnosed among 15- to 29
      year-olds. This pilot study assessed behaviors, barriers, and beliefs relevant to
      sun exposure and protective behaviors. PARTICIPANTS: The sample comprised 153
      undergraduate students at a large state university in western New York. METHODS:
      Participants completed an online survey about sun safety habits, barriers to
      using sunblock, and beliefs about tanning and sun exposure. RESULTS: Response
      rate was 90.8% (n = 139). Most students (87.8%) reportedly spent >= 3 hours per
      day outside in the summer, but only 17.3% reported always using sunblock during
      this time. Sixty percent reported recent indoor tanning and 41% reported more
      than 10 lifetime sunburns. The greatest barrier to using sunblock was forgetting
      (84.2%). CONCLUSIONS: Demographics coupled with inconsistent and low levels of
      sunblock use, high annual prevalence of indoor tanning, and multiple lifetime
      sunburns indicate that this sample is at high risk for skin cancer.

PMID- 22420704
TI  - A review of multicomponent interventions to prevent and control tobacco use among
      college students.
AB  - OBJECTIVE: Multicomponent tobacco control programs have been implemented at the
      state and community levels and have led to a reduction in tobacco use. The
      purpose was to review the public health research literature on tobacco prevention
      and control programs on college campuses and derive evidence-based implications
      for comprehensive program implementation. METHODS: MEDLINE, PsycINFO, ERIC, and
      PubMed databases were used to search the research literature concerning tobacco
      prevention and control programs conducted on college campuses published between
      2000 and 2009. RESULTS: No studies were found that implemented all 5 recommended
      components of a comprehensive program. Tobacco control programs containing policy
      and prevention education were used the most and promotion of tobacco-free
      environments and banning sales of tobacco products were used the least.
      CONCLUSION: The review suggests that despite the recommendation of comprehensive
      tobacco control programs to reduce tobacco use on college campuses, few
      institutions have implemented and evaluated programs consisting of multiple
      components.

PMID- 22420706
TI  - Position statement on tobacco on college and university campuses.

PMID- 22420705
TI  - Collegiate-based emergency medical service: impact on alcohol-related emergency
      department transports at a small liberal arts college.
AB  - OBJECTIVE: The authors examined the impact of a collegiate-based emergency
      medical service (CBEMS) on the frequency of emergency department (ED) transports.
      PARTICIPANTS: Students transported to the ED for acute alcohol intoxication
      during the Fall 2008 and the Fall 2009 semesters (N = 50). METHODS: The frequency
      of students receiving transportation to a hospital ED and the reported blood
      alcohol content (BAC) levels during the initial operational semester of the CBEMS
      were compared to those values over the same time period the previous year.
      RESULTS: More than twice the number of students was transported to the ED
      following the introduction of CBEMS. There was no change in mean BAC levels.
      CONCLUSIONS: CBEMS could promote a culture conducive to increased reporting
      behavior, which makes the campus safer. Similar BAC levels suggest that the
      degree of intoxication was similar for the 2 reporting periods, but students
      sought emergency assistance more frequently following the inception of CBEMS.

PMID- 22420707
TI  - Relations of inattention and hyperactivity/impulsivity to preadolescent peer
      functioning: the mediating roles of aggressive and prosocial behaviors.
AB  - This study examined the structural relations of preadolescents' inattention and
      hyperactivity/impulsivity, aggressive and prosocial behaviors, and peer
      functioning. There were 739 fourth (n = 239) and fifth (n = 500) graders (52.23%
      boys) in Taiwan who participated in this study. Preadolescents' inattention and
      hyperactivity/impulsivity were assessed using parent reports on the Swanson,
      Nolan, and Pelham IV Rating Scale. Aggressive behaviors, including physical
      aggression and relational aggression, and prosocial behaviors were assessed using
      teacher and peer reports. Peer acceptance and the number of reciprocated
      friendships were obtained through peer nomination administered 6 months later
      after initial assessment and were combined to assess children's peer functioning.
      Results of structural equation modeling demonstrated that inattention was
      indirectly linked to impaired peer functioning through low levels of prosocial
      behavior, regardless of gender. In addition, inattention was directly related to
      less optimal peer functioning only for girls. Hyperactivity/impulsivity was
      neither directly nor indirectly related to impaired peer functioning in boys,
      although it was related to more physical and relational aggression. However, for
      girls, a positive and direct path existed between hyperactivity and peer
      functioning. Further, hyperactivity in girls was associated with more physical
      aggression, which in turn led to poorer peer functioning. These findings
      suggested that the processes related to each core domain of ADHD and peer
      functioning may be varied, depending on the mediating factors (e.g., aggression
      or prosocial behavior) and gender.

PMID- 22420708
TI  - Benzylic phosphates as electrophiles in the palladium-catalyzed asymmetric
      benzylation of azlactones.
AB  - Palladium-catalyzed asymmetric benzylation has been demonstrated with azlactones
      as prochiral nucleophiles in the presence of chiral bisphosphine ligands.
      Benzylic electrophiles are utilized under two sets of reaction conditions to
      construct a new tetrasubstituted stereocenter. Electron density of the phenyl
      ring dictates the reaction conditions, including the leaving group. The reported
      methodology represents a novel asymmetric carbon-carbon bond formation in an
      amino acid precursor.

PMID- 22420709
TI  - Local formularies.
AB  - The widespread availability of authoritative guidance on prescribing from a wide
      variety of international and national bodies calls into question the need for
      additional local formulary advice. This article describes contemporary local
      formulary management in the United Kingdom and discusses the areas where local
      decision making remains valuable. Local formularies can fulfil important roles
      which justify their continued existence, including ensuring local ownership and
      acceptance of advice, rapid dissemination of information, responsiveness to local
      circumstances and service design, sensitivity to local pricing arrangements and
      close professional links with commissioners, pharmacists and prescribers.

PMID- 22420710
TI  - Percutaneous reduction and fixation of an intra-articular calcaneal fracture
      using an inflatable bone tamp: description of a novel and safe technique.
AB  - Calcaneal fractures are common injuries involving the hind foot and often a
      source of significant long-term morbidity. Treatment options have changed
      throughout the ages from periods of preferred nonoperative management to closed
      reduction with a mallet, and more recently, open reduction and anatomic internal
      fixation. The current treatment of choice; however, is often debated, as open
      management of these fractures carries many risks to include wound breakdown and
      infection. A less invasive form of surgical management through small incisions,
      while maintaining the ability to obtain joint congruency, anatomic alignment, and
      restore calcaneal height and width would be ideal. We propose a novel form of
      fracture reduction using an inflatable bone tamp and percutaneous fracture
      fixation. Preoperative planning and experienced fluoroscopy is crucial to
      successful management using this method. Although we achieved successful
      radiographic outcome in this case, long-term functional outcome of this technique
      are yet to be published.

PMID- 22420711
TI  - Biologics in organ transplantation.
AB  - The last two decades have witnessed a pandemic in antibody development, with over
      600 entering clinical studies and a total of 28 approved by the FDA and European
      Union. The incorporation of biologics in transplantation has made a significant
      impact on allograft survival. Herein, we review the armamentarium of clinical and
      preclinical biologics used for organ transplantation--with the exception of
      belatacept--from depleting and IL-2R targeting induction agents to costimulation
      blockade, B-cell therapeutics, BAFF and complement inhibition, anti-adhesion, and
      anti-cytokine approaches. While individual agents may be insufficient for
      tolerance induction, they provide possibilities for reduction of steroid or
      calcineurin inhibitor use, alternatives to rejection episodes refractory to
      conventional therapies, and specialized immunosuppression for highly sensitized
      patients.

PMID- 22420712
TI  - Determination of the influence of dispersion pattern of pesticide-resistant
      individuals on the reliability of resistance estimates using different sampling
      plans.
AB  - Pesticide resistance monitoring includes resistance detection and subsequent
      documentation/ measurement. Resistance detection would require at least one (>=1)
      resistant individual(s) to be present in a sample to initiate management
      strategies. Resistance documentation, on the other hand, would attempt to get an
      estimate of the entire population (>=90%) of the resistant individuals. A
      computer simulation model was used to compare the efficiency of simple random and
      systematic sampling plans to detect resistant individuals and to document their
      frequencies when the resistant individuals were randomly or patchily distributed.
      A patchy dispersion pattern of resistant individuals influenced the sampling
      efficiency of systematic sampling plans while the efficiency of random sampling
      was independent of such patchiness. When resistant individuals were randomly
      distributed, sample sizes required to detect at least one resistant individual
      (resistance detection) with a probability of 0.95 were 300 (1%) and 50 (10% and
      20%); whereas, when resistant individuals were patchily distributed, using
      systematic sampling, sample sizes required for such detection were 6000 (1%), 600
      (10%) and 300 (20%). Sample sizes of 900 and 400 would be required to detect
      >=90% of resistant individuals (resistance documentation) with a probability of
      0.95 when resistant individuals were randomly dispersed and present at a
      frequency of 10% and 20%, respectively; whereas, when resistant individuals were
      patchily distributed, using systematic sampling, a sample size of 3000 and 1500,
      respectively, was necessary. Small sample sizes either underestimated or
      overestimated the resistance frequency. A simple random sampling plan is,
      therefore, recommended for insecticide resistance detection and subsequent
      documentation. 

PMID- 22420713
TI  - Effect of nonenzymatic glycosylation on the magnetic resonance imaging (MRI)
      contrast agent binding to human serum albumin.
AB  - Enhanced nonenzymatic glycosylation (NEG) of human serum albumin (HSA) is
      observed in diabetic patients. This modifies some of the physiological functions
      of HSA, as the binding of ligands. Some gadolinium complexes, commonly used as
      MRI contrast agents, have a high affinity for HSA, which enhances their efficacy.
      The aim of this study is to evaluate the possible influence of the NEG of HSA on
      its affinity for some gadolinium chelates.

PMID- 22420714
TI  - The response of PKD1L3/PKD2L1 to acid stimuli is inhibited by capsaicin and its
      pungent analogs.
AB  - Polycystic kidney disease (PKD) 2L1 protein is a member of the transient receptor
      potential (TRP) ion channel family. In circumvallate and foliate papillae, PKD2L1
      is coexpressed with PKD1L3. PKD2L1 and PKD1L3 interact through their
      transmembrane domain and the resulting heteromer PKD1L3/PKD2L1 owns a unique
      channel property called 'off-responses' to acid stimulation, although PKD2L1 does
      not own this property by itself. To define the pharmacological properties of the
      PKD1L3/PKD2L1 channel, we developed a new method to effectively evaluate channel
      activity using human embryonic kidney 293T cells in which the channel was
      heterologously expressed. This method was applied to screen substances that
      potentially regulate it. We found that capsaicin and its analogs, which are TRPV1
      agonists, inhibited the response to acid stimuli and that the capsaicin
      inhibition was reversible with an IC(50) of 32.5 MUm. Capsaicin and its analogs
      are thus useful tools for physiological analysis of PKD1L3/PKD2L1 function.

PMID- 22420716
TI  - The MU3 model of acids and bases: extending the Lewis theory to intermetallics.
AB  - A central challenge in the design of new metallic materials is the elucidation of
      the chemical factors underlying the structures of intermetallic compounds.
      Analogies to molecular bonding phenomena, such as the Zintl concept, have proven
      very productive in approaching this goal. In this Article, we extend a
      foundational concept of molecular chemistry to intermetallics: the Lewis theory
      of acids and bases. The connection is developed through the method of moments, as
      applied to DFT-calibrated Huckel calculations. We begin by illustrating that the
      third and fourth moments (MU(3) and MU(4)) of the electronic density of states
      (DOS) distribution tune the properties of a pseudogap. MU(3) controls the balance
      of states above and below the DOS minimum, with MU(4) then determining the
      minimum's depth. In this way, MU(3) predicts an ideal occupancy for the DOS
      distribution. The MU(3)-ideal electron count is used to forge a link between the
      reactivity of transition metals toward intermetallic phase formation, and that of
      Lewis acids and bases toward adduct formation. This is accomplished through a
      moments-based definition of acidity which classifies systems that are electron
      poor relative to the MU(3)-ideal as MU(3)-acidic, and those that are electron
      rich as MU(3)-basic. The reaction of MU(3) acids and bases, whether in the
      formation of a Lewis acid/base adduct or an intermetallic phase, tends to
      neutralize the MU(3) acidity or basicity of the reactants. This MU(3)
      neutralization is traced to the influence of electronegativity differences at
      heteroatomic contacts on the projected DOS curves of the atoms involved. The role
      of MU(3)-acid/base interactions in intermetallic phases is demonstrated through
      the examination of 23 binary phases forming between 3d metals, the stability
      range of the CsCl type, and structural trends within the Ti-Ni system.

PMID- 22420715
TI  - Gender and race influence metabolic benefits of fitness in children: a cross
      sectional study.
AB  - BACKGROUND: Increasing obesity and poor cardiovascular fitness (CVF) contribute
      to higher rates of type 2 diabetes mellitus (T2DM) in children. While the
      relative contributions of fitness and body fat on development of insulin
      resistance (IR) in children and adolescents remains unresolved, gender- and race
      specific differences likely exist in the degree to which CVF influences IR and
      risk for T2DM. Better understanding of how gender and race affect interactions
      between body fat, CVF, and metabolic health would be helpful in designing
      effective and targeted strategies to reduce obesity-associated disease risk. We
      evaluated whether metabolic benefits of fitness on reducing inflammation and
      insulin resistance (IR) are affected by gender and race. METHODS: This cross
      sectional study included 203 healthy children (mean age 12.2 y, 50% male, 46% non
      Hispanic white (NHW), 54% racially diverse (RD)). Fasting insulin, glucose,
      hsCRP, and adiponectin were measured; race was self-reported; cardiovascular
      fitness (CVF) was evaluated by the Progressive Aerobic Cardiovascular Endurance
      Run. Associations between inflammation and gender, race, and CVF were evaluated
      using analysis of covariance. Multivariate regression analysis identified
      independent predictors of IR. RESULTS: Fitness and inflammation were inversely
      related in both males and females (p < 0.01); this effect was marginally stronger
      in RD children (p = 0.06) and non-overweight males (p = 0.07). High BMI (p <
      0.001), low fitness (p = 0.006), and (female) gender (p = 0.003) were
      independently associated with higher HOMA-IR. In males, BMI and fitness, but not
      race independently predicted HOMA-IR. In females, BMI and race, but not fitness
      independently predicted HOMA-IR. CONCLUSIONS: In middle school children, the
      beneficial effects of fitness vary based on gender and race. High CVF has an
      enhanced anti-inflammatory effect in male and RD children. While BMI is the
      strongest predictor of IR in the study group as a whole, fitness is a significant
      predictor of IR only in males, and race is a significant predictor of IR only in
      females.

PMID- 22420717
TI  - A randomised comparison of the LMA SupremeTM and LMAProSealTM in children.
AB  - We conducted a randomised trial comparing the size-2 LMA SupremeTM with the LMA
      ProSealTM in 60 children undergoing surgery. The outcomes measured were airway
      leak pressure, ease and time for insertion, fibreoptic examination, incidence of
      gastric insufflation, ease of gastric tube placement, quality of the airway
      during anaesthetic maintenance and complications. There were no statistically
      significant differences between the LMA Supreme and LMA ProSeal in median (IQR
      [range]) insertion time (12 (10-15 [7-18]) s vs 12 (10-13 [8-25]) s; p = 0.90),
      airway leak pressures (19 (16-21 [12-30]) cmH(2) O vs 18 (16-24 [10-34]) cmH(2)
      O; p = 0.55), fibreoptic position of the airway or drain tube, ease of gastric
      access and complications. Both devices provided effective ventilation requiring
      minimal airway manipulation. The LMA Supreme can be a useful alternative to the
      LMA ProSeal when single-use supraglottic devices with gastric access capabilities
      are required.

PMID- 22420718
TI  - Enhanced performance of biodegradable poly(butylene succinate)/graphene oxide
      nanocomposites via in situ polymerization.
AB  - Poly(butylene succinate) (PBS)/graphene oxide (GO) nanocomposites were facilely
      prepared via in situ polymerization. The properties of the nanocomposites were
      studied using FTIR, XRD, and (1)H NMR, and the state of dispersion of GO in the
      PBS matrix was examined by SEM. The crystallization and melting behavior of the
      PBS matrix in the presence of dispersed GO nanosheets have been studied by DSC
      and polarized optical microscopy. Through the mechnical testing machine and DMA,
      PBS/GO nanocomposites with 3% GO have shown a 43% increase in tensile strength
      and a 45% improvement in storage modulus. This high performance of the
      nanocomposites is mainly attributed to the high strength of graphene oxide
      combined with the strong interfacial interactions in the uniformly dispersed
      PBS/GO nanocomposites.

PMID- 22420720
TI  - Kidney paired donation: a payer perspective.
AB  - Kidney transplantation is the most cost-effective and clinically effective form
      of renal replacement therapy. Due to long wait times for deceased donors, kidney
      transplantation is not available to many patients with incompatible living
      donors. Increased access to kidney transplantation is a shared goal that can be
      achieved through kidney paired donation (KPD). A single, national system of KPD
      administered to a set of clinical and ethical standards determined by a consensus
      of stakeholders including recipients, donors, providers, payers and the United
      States federal government will provide the best opportunity to offer kidney
      transplantation to the most people and particularly to those currently unlikely
      to receive a transplant. We propose that this system will use uniform tissue
      typing algorithms and a computerized donor and recipient matching program using a
      national pool of willing donors. The proposed system can be managed best through
      a single administrative structure that takes advantage of uniform donor
      evaluation and management with a standardized organ acquisition charge that
      recognizes that the current lack of standardization contributes to delays in
      transplantation and payment to programs. This program will use the existing Organ
      Procurement Organization infrastructure to manage the logistics of organ
      acquisition, transportation and billing.

PMID- 22420719
TI  - Biologics in oral medicine: oral Crohn's disease and orofacial granulomatosis.
AB  - Antitumour necrosis factor (TNF-alpha) therapy has a potential to benefit
      patients with oral lesions of Crohn's disease (CD) and patients with orofacial
      granulomatosis (OFG). The most appropriate use would appear to be in patients
      with severe or multisystem features, where other available agents have failed or
      have been associated with adverse effects. TNF-alpha antagonists (infliximab in
      particular) have a role in the management of orofacial CD and OFG, but potential
      adverse effects of TNF-alpha antagonists include acute infusion reactions,
      infection and increased risk of malignancy. Thus, a full risk-benefit analysis is
      indicated, with patient selection, use and subsequent monitoring coordinated with
      gastroenterologists with appropriate training and experience in biological
      therapies.

PMID- 22420721
TI  - Securing intensive care: towards a better understanding of intensive care nurses'
      perceived work pressure and turnover intention.
AB  - AIM: To provide insight into the individual and contextual factors that are
      related to intensive care nursing staff perceptions of work pressure and
      turnover. BACKGROUND: Hospitals are facing a shortage of intensive care nurses
      that will only become more pressing owing to demographic changes. Nurses'
      sickness absence and turnover are considered important threats to the supply of
      intensive care. DESIGN: A quantitative, cross-sectional research design was used
      that was preceded by a qualitative, explorative study. METHOD: First, interviews
      and observations took place to better understand intensive care nurses' work
      situation. Next, quantitative data were obtained in 2010 from 461 Dutch qualified
      intensive care nurses who completed a questionnaire. FINDINGS: The outcomes of
      multiple regression analyses indicated that nurses' perceptions of work pressure
      were predicted by emotional demands, physical demands, threats from patients'
      relatives, social support and autonomy. Turnover intention was predicted by age,
      ability to deal with night shifts, social support and development opportunities.
      CONCLUSIONS: Given the importance of the availability of staff to secure
      intensive care, this study indicates that hospitals should pay more attention to
      intensive care nurses' work situation. Decreasing emotional and physical demands
      and increasing nurses' development opportunities are some of the measures
      hospitals can take to create a work environment that better accommodates the
      needs of their intensive care nursing staff.

PMID- 22420722
TI  - Thomas A. Seemayer.

PMID- 22420723
TI  - Kazuaki Misugi.

PMID- 22420724
TI  - Vascular and perivascular lesions of skin and soft tissues in children and
      adolescents.
AB  - Vascular anomalies in children and adolescents are the most common soft tissue
      lesions and include reactive, malformative, and neoplastic tumefactions, with a
      full spectrum of benign, intermediate, and malignant neoplasms. These lesions are
      diagnostically challenging because of morphologic complexity and recent changes
      in classification systems, some of which are based on clinical features and
      others on pathologic findings. In recent decades, there have been significant
      advances in clinical diagnosis, development of new therapies, and a better
      understanding of the genetic aspects of vascular biology and syndromes that
      include unusual vascular proliferations. Most vascular lesions in children and
      adolescents are benign, although the intermediate locally aggressive and
      intermediate rarely metastasizing neoplasms are important to distinguish from
      benign and malignant mimics. Morphologic recognition of a vasoproliferative
      lesion is straightforward in most instances, and conventional morphology remains
      the cornerstone for a specific diagnosis. However, pathologic examination is
      enhanced by adjunctive techniques, especially immunohistochemistry to
      characterize the type of vessels involved. Multifocality may cause some
      uncertainty regarding the assignment of "benign" or "malignant." However,
      increased interest in vascular anomalies, clinical expertise, and imaging
      technology have contributed greatly to our understanding of these disorders to
      the extent that in most vascular malformations and in many tumors, a diagnosis is
      made clinically and biopsy is not required for diagnosis. The importance of close
      collaboration between the clinical team and the pathologist cannot be
      overemphasized. For some lesions, a diagnosis is not possible from evaluation of
      histopathology alone, and in a subset of these, a specific diagnosis may not be
      possible even after all assembled data have been reviewed. In such instances, a
      consensus diagnosis in conjunction with clinical colleagues guides therapy. The
      purpose of this review is to delineate the clinicopathologic features of vascular
      lesions in children and adolescents with an emphasis on their unique aspects, use
      of diagnostic adjuncts, and differential diagnosis.

PMID- 22420725
TI  - Neurogenic tumors of soft tissue.
AB  - Neurogenic tumors are an uncommon yet important category of soft tissue tumors in
      children and adolescents because of their frequent association with various
      genetic syndromes. The heterogeneous cellular composition of the peripheral nerve
      and the wide metaplastic capacity of the neural crest and its derivatives
      generate a variety of neoplasms with neurogenic differentiation. This article
      reviews the clinicopathologic features and differential diagnosis of neurogenic
      tumors in the first two decades of life, and highlights use of selected ancillary
      methods for diagnosis.

PMID- 22420726
TI  - Ewing sarcoma/peripheral primitive neuroectodermal tumor and related tumors.
AB  - Ewing sarcoma/peripheral primitive neuroectodermal tumor (EWS/pPNET) and other
      tumors with EWS gene rearrangements encompass a malignant and intermediate
      neoplasm with a broad anatomic distribution and a wide age range but a
      predilection for soft tissue in children, adolescents, and young adults. The
      overlapping histologic, immunohistochemical and cytogenetic and molecular genetic
      features create diagnostic challenges despite significant clinical and prognostic
      differences. Ewing sarcoma is the 3rd most common sarcoma in children and
      adolescents, and desmoplastic small round cell tumor is a rare neoplasm that
      occurs more often in older children, adolescents, and young adults. Pathologic
      examination is complemented by immunohistochemistry, cytogenetics, and molecular
      genetics. This article reviews the clinicopathologic features of EWS/pPNET and
      desmoplastic small round cell tumor in the spectrum of tumors with EWS gene
      rearrangements. Other tumors with different histopathologic features and an EWS
      gene rearrangement are discussed elsewhere in this volume.

PMID- 22420727
TI  - Fibroblastic and myofibroblastic tumors in children and adolescents.
AB  - Fibroblastic and myofibroblastic tumors in children and adolescents are a
      relatively common group of soft tissue proliferations that range from reactive to
      hamartomatous to neoplastic, with a full spectrum of benign, intermediate, and
      malignant neoplasms. These lesions are diagnostically challenging because of
      morphologic and immunohistochemical overlap, despite significant clinical,
      genetic, and prognostic differences. The fibromatoses are a major subgroup, and
      all types of fibromatoses can occur in the 1st 2 decades of life. Intermediate
      and malignant fibroblastic-myofibroblastic tumors are an important group that
      includes variants of fibrosarcoma and other tumors with recurrent cytogenetic or
      molecular genetic abnormalities and low metastatic potential. Pathologic
      examination is enhanced by adjunct techniques, such as immunohistochemistry,
      cytogenetics, and molecular genetics, although morphology provides the ultimate
      criteria for a specific diagnosis. This article reviews the clinicopathologic
      features of fibroblastic and myofibroblastic tumors with an emphasis on the
      unique aspects of these neoplasms in children and adolescents, the use of
      diagnostic adjuncts, and differential diagnoses.

PMID- 22420728
TI  - Fibrohistiocytic tumors and related neoplasms in children and adolescents.
AB  - Fibrohistiocytic tumors (FHTs) in children and adolescents range from the benign
      fibrous histiocytoma, or dermatofibroma, to a variety of intermediate and
      malignant neoplasms, such as dermatofibrosarcoma protruberans and high-grade
      undifferentiated pleomorphic sarcoma (malignant fibrous histiocytoma). Those
      tumors as a group are comprised of fibroblasts, myofibroblasts, and histiocytes
      dendritic cells with a variably prominent inflammatory infiltrate consisting of
      lymphocytes and eosinophils. Dendritic cells are also a major constituent of
      another group of neoplasms that include Langerhans cell histiocytosis, follicular
      and interdigitating cell sarcomas, and juvenile xanthogranuloma. These latter
      tumors are considered in this discussion for the sake of differential diagnosis
      and their possible histogenetic relationship to FHTs. Recent studies have
      suggested that the relationship between the fibroblast and histiocyte in the FHTs
      may reflect the intrinsic capacity to transdifferentiate from one to the other
      morphologic and functional state. The so-called "facultative fibroblast," as a
      cell with fibroblastic and histiocytic properties, was discussed in the context
      of the fibrous xanthoma 50 years ago. Possibly the entire histogenetic concept of
      FHTs should be reconsidered in light of current studies.

PMID- 22420729
TI  - Myogenic tumors in children and adolescents.
AB  - Neoplasms of striated and smooth muscle in children are a diverse group of
      neoplasms that have some unique aspects in contrast to these tumors in adults.
      Rhabdomyosarcoma is the most common soft tissue sarcoma of infancy and childhood
      and is relatively common in adolescents. In contrast, smooth muscle tumors are
      relatively rare, and the various types of rhabdomyoma and smooth and skeletal
      muscle hamartomas are very uncommon. In recent years, the understanding of the
      pathologic and genetic aspects of rhabdomyosarcoma has been enhanced by adjunct
      techniques, such as immunohistochemistry and cytogenetic or molecular genetic
      analysis. The current classification of rhabdomyosarcoma emphasizes the
      histologic-prognostic correlations. This article reviews the clinicopathologic
      features of striated and smooth muscle tumors with an emphasis on the unique
      aspects of these neoplasms in children and adolescents and the differential
      diagnosis.

PMID- 22420730
TI  - Adipose and myxoid tumors of childhood and adolescence.
AB  - Adipose and myxoid tumors in children are an unusual and challenging group of
      neoplasms that have some unique aspects in contrast to these tumors in adults.
      Less than 10% of soft tissue neoplasms in the 1st 2 decades of life have an
      adipose phenotype and most are benign. The most common are various types of
      lipoma and lipoblastoma. Liposarcoma in young patients is rare and has a
      distinctive distribution of histologic subtypes, including classic myxoid
      liposarcoma, and unusual variants, such as pleomorphic-myxoid liposarcoma.
      Pathologic examination enhanced by adjunct techniques, such as
      immunohistochemistry and cytogenetic or molecular genetic studies, is useful for
      classification of difficult cases. Myxoid tumors can overlap with adipose tumors
      and are included in this review because of the morphologic similarities and
      importance of diagnostic accuracy. This article reviews the clinicopathologic
      features of adipose and myxoid tumors with an emphasis on the unique aspects of
      these neoplasms in children and adolescents and the differential diagnosis.

PMID- 22420731
TI  - Extraskeletal cartilaginous, osseous, and chordoid tumors in children and
      adolescents.
AB  - Extraskeletal cartilaginous, osseous, and chordoid tumors are extraordinarily
      rare in children and adolescents. These lesions are diagnostically challenging
      due to their rarity and their overlap with metastatic osteosarcoma, reactive or
      metabolic calcifying and bone-forming masses, various pseudosarcomatous
      proliferations such as myositis ossificans, and other rare genetic or metabolic
      disorders. This article reviews the clinicopathologic features and differential
      diagnosis of extraskeletal cartilaginous, osseous, and chordoid neoplasms in the
      first two decades of life and highlights the use of diagnostic adjuncts.

PMID- 22420732
TI  - Soft tissue tumors of uncertain origin.
AB  - Many soft tissue tumors of childhood lack obvious differentiation toward a
      defined mesenchymal tissue type or have a phenotype that does not correspond to
      any defined normal tissue. These challenging tumors are currently regarded as
      neoplasms of uncertain differentiation. Nonetheless, there have been great
      strides in the understanding of their pathologic and genetic features and
      biologic underpinnings. The application of new genetic information to the
      pathologic diagnosis among this group of tumors is an emerging area in diagnostic
      pediatric pathology. This article reviews the clinicopathologic features of
      tumors of uncertain and/or miscellaneous origin, with an emphasis on the unique
      aspects of these neoplasms in children and adolescents, use of diagnostic
      adjuncts, and differential diagnosis.

PMID- 22420733
TI  - Effect of cerclage on labor course and obstetric outcome: a case-control study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of cervical
      cerclage on labor course and obstetric outcome. METHODS: In a retrospective case
      control study, we compared labor course, total labor duration, and obstetric
      complications in 127 women who received cervical cerclage with 254 controls.
      RESULTS: There was no significant difference in the duration of the first stage
      of labor (477 +/- 576 vs. 373 +/- 437 min, p = 0.075) or the second stage of
      labor (18 +/- 17 vs. 20 +/- 19 min, p = 0.287) between the 2 groups. In the
      multivariate analysis, women in the cerclage group were found to be significantly
      more likely to have a prolonged latent phase (odds ratio [OR], 2.802; 95%
      confidence interval [CI], 1.103-7.120; p = 0.030), cervical laceration (OR,
      15.984; 95% CI, 3.169-80.624; p = 0.001), and treatment with tocolytics (OR,
      2.580; 95% CI, 1.217-5.468; p = 0.013) than the control group. No significant
      difference was noted in cesarean delivery rate. CONCLUSIONS: Cervical cerclage is
      more likely to be associated with a prolonged latent phase and minor obstetric
      complications, but not with a difference in the total duration of labor or
      increased cesarean delivery rate.

PMID- 22420734
TI  - Ring enlargement versus selenoetherification on the reaction of allenyl oxindoles
      with selenenylating reagents.
AB  - Lactam-tethered allenols, readily prepared from alpha-oxolactams, were used as
      starting materials for divergent reactivity with selenenylating reagents. Either
      oxycyclization (spirocyclic selenolactams) or ring expansion (selenoquinolones)
      can be achieved through the choice of both reagents and substrates. The
      biological activity of some of the synthesized heterocycles has additionally been
      evaluated in four human cancer cell lines.

PMID- 22420735
TI  - Improved traditional medicines in Mali.

PMID- 22420736
TI  - Earthing the human organism influences bioelectrical processes.
AB  - OBJECTIVES: This article describes interaction of the Earth's mass-electrolytic
      conductor on the electrical environment of human organism-aqueous environment and
      skeleton. In this environment, bioelectrical and bioenergetical processes take
      place. METHODS AND SUBJECTS: Measurements of electric potential on tongue, teeth,
      nails, and in venous blood in subjects earthed and unearthed were conducted in
      Faraday's cage with the use of an electrometer placed outside the cage.
      Measurements were performed in subjects in lying position and in movements of
      standing up and lying down. RESULTS: In the unearthed human organism in the lying
      position, electric potential measured in examined points is around 0  mV. Contact
      of the Earth by a copper conductor with a moistened surface of the human body
      evokes a rapid decrease of electrostatic potential on the body and in venous
      blood to the value of approximately -200  mV. This effect is immediate and
      general. Interruption of contact with the Earth causes a rapid return of the
      potential to its initial values in examined points. Changes in electric potential
      measured in venous blood and on mucosal membrane of the tongue reflect
      alterations in electric potential of the aqueous, electrical environment. Up-and
      down movement of the insulated human organism causes transient changes in
      potential in the human electrical environment. During the same movement, values
      of potential in the electrical environment of an earthed human body remain
      constant. CONCLUSIONS: These results indicate that up-and-down movement and the
      elimination of potentials in the electrical environment of the human organism by
      the Earth's mass may play a fundamental role in regulation of bioelectrical and
      bioenergetical processes. The Earth's electromagnetohydrodynamic potential is
      responsible for this phenomenon.

PMID- 22420737
TI  - Use of complementary therapies for cancer symptom management: results of the 2007
      National Health Interview Survey.
AB  - OBJECTIVES: Complementary therapies are often used as adjuncts to conventional
      treatment by individuals with cancer. Patterns of use of these practices and
      products represent important data for health care providers in delivering
      adequate patient care. DESIGN: This study compared use of complementary therapies
      between the cancer and noncancer populations in the United States through
      secondary analyses of the 2007 National Health Interview Survey data. The
      analysis compared use by cancer survivors (those individuals self-reporting a
      diagnosis of cancer; n=1785) and individuals without cancer (n=21,585), as well
      as self-report of symptoms affecting health-related quality of life (HQoL).
      RESULTS: Data suggest similar patterns of use between cancer survivors and the
      general population; however, a greater percentage of cancer survivors use
      complementary modalities. Individuals with cancer reported a greater percentage
      of use of complementary therapies overall, with cancer status significantly
      associated with ever having used complementary and alternative medicine
      (p<0.001). The five most common complementary practices and products used by
      individuals with cancer and controls were vitamin/mineral supplements, prayer for
      self, intercessory prayer, chiropractic/osteopathic manipulation, and herbal
      therapies. Additionally, as might be expected, individuals with cancer experience
      greater frequency of deleterious symptoms associated with decreased HQoL.
      Individuals with cancer were more likely to sleep fewer than 7 hours (p=0.0108)
      or greater than 9 hours (p=0.0108), and have increased insomnia (p<0.001),
      excessive sleepiness (p<0.001), depression (p<0.001), and anxiety (p<0.001)
      versus those without cancer. CONCLUSIONS: The current findings may inform health
      care providers about the use of complementary and integrative practices and
      products by patients with cancer in an effort to manage symptoms of the disease.
      Additionally, these results may also be used to promote research to define the
      merits of the use of such complementary and integrative practices and products.

PMID- 22420739
TI  - Confidence in clinical practice of Chinese medicine degree graduates 1 year after
      graduation: a pilot study.
AB  - BACKGROUND: The issue of transition from student to practitioner of Chinese
      medicine (CM) in Australia and other Western countries has received little formal
      attention. Workforce studies, while not up to date nationally in Australia,
      suggest that the majority of CM practitioners practice as sole practitioners or
      in small practices. Data from the state of Victoria suggest that a significant
      proportion of the CM workforce is relatively new to the profession. It is not
      known how many graduates successfully enter the workforce and importantly, remain
      in it. OBJECTIVES: An initial survey of final-year bachelor degree CM students in
      Australian education institutions in 2008 suggested that students felt "somewhat"
      prepared for clinical practice in eight dimensions of clinical practice. The
      authors conducted a follow-up study to this initial one, seeking to investigate
      perceptions of confidence in CM graduates in various aspects of clinical practice
      within the first year of completing their degree. METHODS: A content-validated
      survey based on the previous study was distributed to a subset of 30 graduates
      from the original study cohort who had indicated a willingness to participate in
      this follow-up survey. RESULTS: There were a small number of responses (n=12),
      limiting the usefulness of the quantitative questions. However, some interesting
      qualitative outcomes from the long-answer part of the survey support findings
      from the previous study that recent practitioners would like more clinical
      experience, as well as support in developing their business and interpersonal
      skills, and the option to participate in a professional mentoring arrangement.
      CONCLUSIONS: Results of this study suggest that both education providers and
      professional associations may be able to play important and complementary roles
      in assisting CM students to successfully transition into the workforce. If CM is
      to continue to develop as a profession in Australia, it will be important that
      more attention be given to how to assist new graduates to successfully transition
      into and remain in clinical practice.

PMID- 22420738
TI  - Stress reduction with osteopathy assessed with GDV electrophotonic imaging:
      effects of osteopathy treatment.
AB  - OBJECTIVES: The purpose of this study is to explore how osteopathy treatments
      influence certain measurable aspects of the human biofield; namely, various
      calculated parameters of finger corona discharge patterns produced by high
      voltage electrophotography. METHODS: The Gas Discharge Visualization camera was
      used to assess subjects before and after osteopathy treatment. Thirty-three (33)
      apparently healthy adults (20-56 years old) took part in the study. The patterns
      of light emitted from the subjects' fingertips were digitally recorded and
      computer analyzed. Parameters including normalized area, brightness, and right-
      and left-hand integrals were calculated and statistically compared. RESULTS: Most
      of the recipients of these osteopathic treatments experienced increase in
      fingertip florescence area and average intensity, reduction in stress levels, and
      improved blood pressure measurements. With all of these parameters simultaneously
      improving, the patients received a good benefit from these sessions. CONCLUSIONS:
      Virtually all subjects were in a good mood after treatment. Many of them had pain
      and muscle tension that disappeared. These changes were reflected in all
      parameters analyzed, in both psychosomatic and somatic states. Thus, osteopathic
      manipulations as administered in these two studies provide good, lasting
      relaxation. This study also provides the interesting observation that daily
      relaxation practices done by Dr. Paoletti enable him to work hard without
      additional stress.

PMID- 22420740
TI  - Comparing the health status of U.S. taijiquan and qigong practitioners to a
      national survey sample across ages.
AB  - PURPOSE: The purpose of this study is to examine and compare health status across
      ages using a volunteer sample of U.S. Taijiquan and Qigong (TQG) practitioners
      (N=120; age range=24-83, M=54.77) and a nationally representative sample
      (N=414,629; age range=18-99, M=54.86) collected by the Centers for Disease
      Control and Prevention (CDC). DESIGN: The study design was cross-sectional,
      between-group comparisons. METHODS: An online survey designed to collect data on
      health-related quality of life (HRQoL), lifestyle variables, and TQG practice
      regimens was administered to a volunteer sample of taijiquan practitioners. A
      link to the survey was e-mailed to registrants of the International T'ai Chi
      Symposium who further forwarded (snowballed) the link to other practitioners
      across the country and around the world. The HRQoL and demographic sections of
      the survey were adapted from the CDC's Behavioral Risk Factor Surveillance System
      (BRFSS). Taiji practitioner data and BRFSS data were then merged and three groups
      -No Exercise, Some Exercise, and TQG Exercise--were created for the analysis.
      Health status was regressed on age, exercise group membership, and the
      interaction between age and group membership while controlling for income and
      education. RESULTS: After controlling for the effects of income and education, a
      significant interaction effect (p<0.001) was detected between age and group
      membership. Group membership was not a substantial predictor of health among
      younger individuals, but among older adults, substantive and significant between
      group differences appeared, with the TQG group evincing the best average health
      trajectory across ages. CONCLUSIONS: Although this cross-sectional comparison
      cannot establish causality or rule out cohort effects, the extraordinary
      trajectory of health status among TQG practitioners in this U.S. sample is
      significantly better than average exercising and nonexercising U.S. Americans,
      even while controlling for the influence of income and education levels. Lifespan
      developmental theory is utilized to consider several factors beyond the physical
      exercise value of TQG that may be responsible for the exercise group differences.

PMID- 22420741
TI  - Photosynthesis, photorespiration and productivity of wheat and soybean genotypes.
AB  - The results of the numerous measurements obtained during the last 40 years on gas
      exchange rate, photosynthetic carbon metabolism by exposition in 14CO2 and
      activities of primary carbon fixation enzyme, ribulose-1,5-bisphosphate
      carboxylase/oxygenase (RuBPC/O), in various wheat and soybean genotypes grown
      over a wide area in the field and contrasting in photosynthetic traits and
      productivity are presented in this article. It was established that high
      productive wheat genotypes (7-9 t ha-1) with the optimal architectonics possess
      higher rate of CO2 assimilation during the leaf ontogenesis. Along with the high
      rate of photosynthesis, high values of photorespiration are characteristic for
      the high productive genotypes. Genotypes with moderate (4-5 t ha-1) and low (3 t
      ha-1) grain yield are characterized by relatively low rates of both CO2
      assimilation and photorespiration. A value of photorespiration constitutes 28-35%
      of photosynthetic rate in contrasting genotypes. The activities of RuBPC and
      RuBPO were changing in a similar way in the course of the flag leaf and ear
      elements development. High productive genotypes are also characterized by a
      higher rate of biosynthesis and total value of glycine-serine and a higher
      photosynthetic rate. Therefore, contrary to conception arisen during many years
      on the wastefulness of photorespiration, taking into account the versatile
      investigations on different aspects of photorespiration, it was proved that
      photorespiration is one of the evolutionarily developed vital metabolic processes
      in plants and the attempts to reduce this process with the purpose of increasing
      the crop productivity are inconsistent.

PMID- 22420743
TI  - Promoting menstrual health among persian adolescent girls from low socioeconomic
      backgrounds: a quasi-experimental study.
AB  - BACKGROUND: Research in the past decade has revealed average to poor menstrual
      health among many Iranian girls. The present study investigated the effectiveness
      of a health promotion project on improving menstrual health in adolescent girls
      in Iran. METHODS: A quasi-experimental study was conducted to evaluate the
      effectiveness of the health intervention program. A total of 698 students (study
      participants and controls) in several schools in Mazandaran province, Iran were
      included. The project comprised 10 two-hour educational sessions. Educational
      topics included the significance of adolescence, physical and emotional changes
      during adolescence, pubertal and menstruation health and premenstrual syndrome. A
      self-administered questionnaire measuring demographic characteristics, behaviors
      during menstruation, menstrual patterns, sources of information about
      menstruation and personal health data was administered. The questionnaire was
      administered to all participating students after the experimental group received
      the training. RESULTS: Among the most significant results was the impact of
      educational sessions on bathing and genital hygiene. A total of 61.6% in the
      experimental group compared with 49.3% in the control group engaged in usual
      bathing during menstruation (p = 0.002). Individual health status was
      significantly statistically correlated with menstrual health. Attitude towards
      menstruation was also significantly related to menstrual health. CONCLUSIONS: The
      present study confirms that educational interventions, such as the health
      promotion project in this study, can be quite effective in promoting menstrual
      health.

PMID- 22420744
TI  - Application of the new scaling relations and global isomorphism to the study of
      liquid-vapor saturation pressure.
AB  - We apply the new scaling relations and global isomorphism between continuous and
      discrete systems to find of saturation pressure. On this basis, we obtain the
      expression for the saturation pressure containing the critical, Z line parameters
      and two fitting parameters. First we calculate the saturation pressure for a
      number of model systems and real substances the critical parameters for which are
      known and verify that the accuracy is acceptable in a wide liquid-gas temperature
      domain. Then we discuss situation with the saturation pressure for metals
      (aluminum and iron), the critical parameters for which are unknown in advance and
      lie in the domain of parameters still inaccessible for experiments.

PMID- 22420742
TI  - Acute alcohol effects on contextual memory BOLD response: differences based on
      fragmentary blackout history.
AB  - BACKGROUND: Contextual memory, or memory for source details, is an important
      aspect of episodic memory and has been implicated in alcohol-induced fragmentary
      blackouts (FBs). Little is known, however, about how neural functioning during
      contextual memory processes may differ between individuals with and without a
      history of FB. This study examined whether neural activation during a contextual
      memory task differed by history of FB and acute alcohol consumption. METHODS:
      Twenty-four matched individuals with (FB+; n = 12) and without (FB-; n = 12) a
      history of FBs were recruited from a longitudinal study of alcohol use and
      behavioral risks and completed a laboratory beverage challenge followed by 2
      functional magnetic resonance imaging (fMRI) sessions under no alcohol and
      alcohol (breath alcohol concentration = 0.08%) conditions. Task performance and
      brain hemodynamic activity during a block design contextual memory task were
      examined across 48 fMRI sessions. RESULTS: Groups demonstrated no differences in
      performance on the contextual memory task, yet exhibited different brain response
      patterns after alcohol intoxication. A significant FB group by beverage
      interaction emerged in bilateral dorsolateral prefrontal cortex and posterior
      parietal cortex with FB- individuals showing greater blood oxygenation level
      dependent response after alcohol exposure (p < 0.05). CONCLUSIONS: Alcohol had
      differential effects on neural activity for FB+ and FB- individuals during
      recollection of contextual information, perhaps suggesting a neurobiological
      mechanism associated with alcohol-induced FB.

PMID- 22420745
TI  - Biomimetic oxygen reduction by cofacial porphyrins at a liquid-liquid interface.
AB  - Oxygen reduction catalyzed by cofacial metalloporphyrins at the 1,2
      dichlorobenzene-water interface was studied with two lipophilic electron donors
      of similar driving force, 1,1'-dimethylferrocene (DMFc) and tetrathiafulvalene
      (TTF). The reaction produces mainly water and some hydrogen peroxide, but the
      mediator has a significant effect on the selectivity, as DMFc and the porphyrins
      themselves catalyze the decomposition and the further reduction of hydrogen
      peroxide. Density functional theory calculations indicate that the
      biscobaltporphyrin, 4,5-bis[5-(2,8,13,17-tetraethyl-3,7,12,18
      tetramethylporphyrinyl)]-9,9-dimethylxanthene, Co(2)(DPX), actually catalyzes
      oxygen reduction to hydrogen peroxide when oxygen is bound on the "exo" side
      ("dock-on") of the catalyst, while four-electron reduction takes place with
      oxygen bound on the "endo" side ("dock-in") of the molecule. These results can be
      explained by a "dock-on/dock-in" mechanism. The next step for improving
      bioinspired oxygen reduction catalysts would be blocking the "dock-on" path to
      achieve selective four-electron reduction of molecular oxygen.

PMID- 22420746
TI  - Pain and sleep-wake disturbances in adolescents with depressive disorders.
AB  - The aims of this study were to (a) assess and compare sleep disturbances
      (including daytime and nighttime sleep patterns) in adolescents with depressive
      disorders and healthy peers, (b) examine the prevalence of pain in adolescents
      with depressive disorders and healthy peers, and (c) examine pubertal
      development, pain intensity, and depressive symptom severity as predictors of
      sleep disturbance. One hundred six adolescents (46 depressed, 60 healthy), 12 to
      18 years (M = 15.10 years; 67% female; 77% Caucasian) completed subjective
      measures of sleep, presleep arousal, fatigue, and pain. Participants also
      underwent 10 days of actigraphic monitoring to assess nighttime and daytime sleep
      duration, sleep efficiency, and wake after sleep onset. Results indicated that
      youth with depression exhibited greater sleep disturbances on subjective and
      actigraphic sleep variables than healthy controls. Depressed youth also reported
      more frequent and severe pain than healthy youth. Linear regression analysis
      indicated that pain intensity and depressive symptoms predicted worse sleep
      quality across groups. The interaction term was also significant, such that
      adolescents with high levels of depressive symptoms had poor sleep quality when
      pain intensity levels were high. These results indicate that sleep is important
      to assess in youth with depression, and that pain may be an important target for
      sleep intervention in this population.

PMID- 22420748
TI  - Rapid genetic turnover in populations of the insect pest Bemisia tabaci Middle
      East: Asia Minor 1 in an agricultural landscape.
AB  - Organisms differ greatly in dispersal ability, and landscapes differ in
      amenability to an organism's movement. Thus, landscape structure and
      heterogeneity can affect genetic composition of populations. While many
      agricultural pests are known for their ability to disperse rapidly, it is unclear
      how fast and over what spatial scale insect pests might respond to the temporally
      dynamic agricultural landscapes they inhabit. We used population genetic analyses
      of a severe crop pest, a member of the Bemisia tabaci (Hemiptera: Sternorrhyncha:
      Aleyrodoidea: Aleyrodidea) cryptic species complex known as Middle East-Asia
      Minor 1 (commonly known as biotype B), to estimate spatial and temporal genetic
      diversity over four months of the 2006-2007 summer growing season. We examined
      559 individuals from eight sites, which were scored for eight microsatellite
      loci. Temporal genetic structure greatly exceeded spatial structure. There was
      significant temporal change in local genetic composition from the beginning to
      the end of the season accompanied by heterozygote deficits and inbreeding. This
      temporal structure suggests entire cohorts of pests can occupy a large and
      variable agricultural landscape but are rapidly replaced. These rapid genetic
      fluctuations reinforce the concept that agricultural landscapes are dynamic
      mosaics in time and space and may contribute to better decisions for pest and
      insecticide resistance management. 

PMID- 22420747
TI  - In silico modeling of the pore region of a KCNQ4 missense mutant from a patient
      with hearing loss.
AB  - BACKGROUND: Mutation of the voltage-gated potassium channel KCNQ4 causes DFNA2
      type nonsyndromic autosomal dominant sensorineural hearing loss. KCNQ4 is
      expressed predominantly in the auditory sensory outer hair cells, which are
      critical for sound amplification. RESULTS: We sequenced KCNQ4 from Japanese
      patients with sensorineural hearing loss, and identified a novel missense
      mutation encoding a Tyr270His located at the N-terminus of the highly conserved
      pore helix sequence. As this patient was not accessible to us and information
      about them was limited, we used molecular modeling to investigate whether this
      novel mutation is hypothetically pathogenic. A careful examination of an in
      silico structural model of the KCNQ4 pore region revealed that the Tyr270His
      mutation caused an alteration in the electrostatic surface potential of the pore
      helix. CONCLUSION: We propose two possible means by which the Tyr270His mutation
      causes hearing loss: a positively charged His270 side chain might enhance the
      helix dipole moment of the pore helix, thereby destabilizing the helix and/or the
      pore region, or it might disturb transport of K+ through the channel by
      electrostatic repulsion.

PMID- 22420749
TI  - Concept-based learning of personalized prescribing.
AB  - The variability of drug response in different patients can be caused by various
      factors including age, change in renal function, co-medication and genotype.
      Traditionally, these personal variables are considered by clinicians prior to
      issuing a prescription. This paper provides an overview of a process to
      individualize prescribing for a patient with an emphasis on how to train
      (learning) clinicians in skillful rational prescribing. For this purpose the
      6STEP methodology, a concept-based learning strategy to achieve a structured
      therapeutic plan, has been introduced. In contrast to older educational
      approaches which focused primarily on the drugs or the process of prescribing,
      the 6STEP is a patient-centred method resulting in individualized therapy. The
      six interlinked steps provide the (training) prescriber with a structured
      framework that facilitates a rationalized therapeutic decision by focusing on the
      individual patient parameters that influence drug response. Educational tools for
      rational prescribing involve understanding of basic and clinical pharmacological
      principles, practicing to write 6STEP therapeutic plans, learning from feedback
      sessions on these plans and actively obtaining up to date information on drugs
      and therapeutic standards from online resources.

PMID- 22420750
TI  - Carbon dioxide supersaturation promotes primary production in lakes.
AB  - A majority of the world's lakes are supersaturated with respect to carbon dioxide
      (CO(2) ). By experimental manipulation of the CO(2) concentration in
      supersaturated boreal lakes, we demonstrate that phytoplankton primary production
      was up to 10 times higher in supersaturated lake water in comparison with water
      with CO(2) at equilibrium concentrations and that CO(2) , together with
      nutrients, explained most of the variation in pelagic primary production and
      phytoplankton biomass over a wide variety of unproductive lakes. These results
      suggest that phytoplankton can be co-limited by CO(2) and nutrients in
      unproductive lakes. As import of terrestrial organic carbon and its subsequent
      microbial mineralisation in lakes is a driving force of CO(2) -supersaturation
      our results suggest that lake productivity and carbon cycling may respond to
      variations in terrestrial organic carbon export, (e.g. caused by land use or
      climate change) in ways not described before.

PMID- 22420751
TI  - From a cycloheptatrienylzirconium allyl complex to a cycloheptatrienylzirconium
      imidazolin-2-iminato "pogo stick" complex with imido-type reactivity.
AB  - The reaction of the cycloheptatrienylzirconium half-sandwich complex [(eta(7)
      C(7)H(7))ZrCl(tmeda)] (1) (tmeda = N,N,N',N'-tetramethylethylenediamine) with
      Li(Im(Dipp)N), generated from bis(2,6-diisopropylphenyl)imidazolin-2-imine
      (Im(Dipp)NH) with methyllithium, yields the imidazolin-2-iminato complex [(eta(7)
      C(7)H(7))Zr(Im(Dipp)N)(tmeda)] (2). The corresponding tmeda-free complex [(eta(7)
      C(7)H(7))Zr(Im(Dipp)N)] (5) can be synthesized via the 1,3
      bis(trimethylsilyl)allyl complex [(eta(7)-C(7)H(7))Zr{eta(3)
      C(3)H(3)(TMS)(2)}(THF)] (3; TMS = SiMe(3)), which undergoes an acid-base reaction
      with Im(Dipp)NH to form 5 and 1,3-bis(trimethylsilyl)propene. 5 exhibits an
      unusual one-legged piano stool ("pogo stick") geometry with a particularly short
      Zr-N bond of 1.997(2) A. Addition of 2,6-dimethylphenyl or tert-butyl isocyanide
      affords the complexes [(eta(7)-C(7)H(7))Zr(Im(Dipp)N)(CNR)] (R = o-Xy, 6; R = t
      Bu, 7), while the reaction with 2,6-dimethylphenyl isocyanate results in a [2 +
      2] cycloaddition to form the ureato(1-) complex [(eta(7)
      C(7)H(7))Zr{Im(Dipp)N(C?O)N-o-Xy}] (8). 5 can also act as an initiator for the
      ring-opening polymerization of epsilon-caprolactone. These reactivity patterns
      together with density functional theory calculations reveal a marked similarity
      of the bonding in imidazolin-2-iminato and conventional imido transition-metal
      complexes.

PMID- 22420752
TI  - Studies of H3K4me3 demethylation by KDM5B/Jarid1B/PLU1 reveals strong substrate
      recognition in vitro and identifies 2,4-pyridine-dicarboxylic acid as an in vitro
      and in cell inhibitor.
AB  - Dynamic methylations and demethylations of histone lysine residues are important
      for gene regulation and are facilitated by histone methyltransferases and histone
      demethylases (HDMs). KDM5B/Jarid1B/PLU1 is an H3K4me3/me2-specific lysine
      demethylase belonging to the JmjC domain-containing family of histone
      demethylases (JHDMs). Several studies have linked KDM5B to breast, prostate and
      skin cancer, highlighting its potential as a drug target. However, most inhibitor
      studies have focused on other JHDMs, and inhibitors for KDM5B remain to be
      explored. Here, we report the expression, purification and characterization of
      the catalytic core of recombinant KDM5B (ccKDM5B, residues 1-769). We show that
      ccKDM5B, recombinantly expressed in insect cells, demethylates H3K4me3 and
      H3K4me2 in vitro. The kinetic characterization showed that ccKDM5B has an
      apparent Michaelis constant (K(m) (app) ) value of 0.5 MUm for its trimethylated
      substrate H3(1-15)K4me3, a considerably increased apparent substrate affinity
      than reported for related HDMs. Despite the presence of a PHD domain, the
      catalytic activity was not affected by additional methylation at the H3K9
      position, suggesting that in vitro chromatin cross-talk between H3K4 and H3K9
      does not occur for ccKDM5B. Inhibition studies of ccKDM5B showed both in vitro
      and in cell inhibition of ccKDM5B by 2,4-pyridinedicarboxylic acid (2,4-PDCA)
      with a potency similar to that reported for the HDM KDM4C. Structure-guided
      sequence alignment indicated that the binding mode of 2,4-PDCA is conserved
      between KDM4A/C and KDM5B.

PMID- 22420753
TI  - RhoA-mediated signaling in mechanotransduction of osteoblasts.
AB  - Osteoblasts play a pivotal role in load-driven bone formation by activating Wnt
      signaling through a signal from osteocytes as a mechanosensor. Osteoblasts are
      also sensitive to mechanical stimulation, but the role of RhoA, a small GTPase
      involved in the regulation of cytoskeleton adhesion complexes, in
      mechanotransduction of osteoblasts is not completely understood. Using MC3T3-E1
      osteoblast-like cells under 1 hr flow treatment at 10 dyn/cm(2), we examined a
      hypothesis that RhoA signaling mediates the cellular responses to flow-induced
      shear stress. To test the hypothesis, we conducted genome-wide pathway analysis
      and evaluated the role of RhoA in molecular signaling. Activity of RhoA was
      determined with a RhoA biosensor, which determined the activation state of RhoA
      based on a fluorescence resonance energy transfer between CFP and YFP
      fluorophores. A pathway analysis indicated that flow treatment activated
      phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK)
      signaling as well as a circadian regulatory pathway. Western blot analysis
      revealed that in response to flow treatment phosphorylation of Akt in PI3K
      signaling and phosphorylation of p38 and ERK1/2 in MAPK signaling were induced.
      FRET measurement showed that RhoA was activated by flow treatment, and an
      inhibitor to a Rho kinase significantly reduced flow-induced phosphorylation of
      p38, ERK1/2, and Akt as well as flow-driven elevation of the mRNA levels of
      osteopontin and cyclooxygenase-2. Collectively, the result demonstrates that in
      response to 1 hr flow treatment to MC3T3-E1 cells at 10 dyn/cm(2), RhoA plays a
      critical role in activating PI3K and MAPK signaling as well as modulating the
      circadian regulatory pathway.

PMID- 22420754
TI  - Predicting severity and clinical course of acute rejection after liver
      transplantation using blood eosinophil count.
AB  - Acute cellular rejection remains an important source of morbidity after liver
      transplantation, particularly if rejection is moderate or severe, as this usually
      is treated. Currently liver biopsies are seldom performed, so diagnostic
      noninvasive markers would be useful. We evaluated 690 consecutive first liver
      transplant patients to assess whether peripheral eosinophilia could predict
      moderate-severe rejection and its course. A protocol biopsy was performed 6 +/-
      2.5 days after transplant. A second biopsy was taken 6.1 +/- 2 days after the
      first in 487 patients to assess histological improvement. Liver function tests,
      peripheral eosinophil count and changes between first and second biopsy, were
      evaluated using logistic regression. Histological rejection was present in 532
      patients (77.1%), with moderate (30.6%) and severe rejection (3.9%). Peripheral
      eosinophil count was strongly associated with moderate-severe rejection (OR =
      2.15; P = 0.007), although the area under ROC curve (AUROC) was 0.58. On second
      biopsy, rejection improved in 119 (24.4%) patients. The delta in eosinophil count
      between the first and second biopsies was the only independent predictor of
      histological improvement (OR = 3.12; P = 0.001), irrespective of whether bolus
      steroids were used (OR = 2.77; P = 0.004); AUROC was 0.72. Peripheral
      eosinophilia is not sufficiently predictive of moderate-severe histological
      rejection. However the changes in eosinophil count over time can accurately
      predict the histological resolution of rejection.

PMID- 22420755
TI  - Ubiquitin ligases and beyond.

PMID- 22420756
TI  - Production, characterization, and application of monoclonal antibodies specific
      to recombinant (E2) structural protein in antigen-capture ELISA for clinical
      diagnosis of Chikungunya virus.
AB  - The resurgence of Chikungunya (CHIK) virus in the form of an explosive,
      unprecedented epidemic with high virulence and unusual numbers of fatalities has
      created an immense public health concern in recent years. In the absence of an
      effective vaccine and specific antiviral therapy, early accurate diagnosis is
      essential for the best patient management. The present study describes the
      production and characterization of high-affinity and selective monoclonal
      antibodies (Mabs) against recombinant E2 protein (rE2) of the CHIK virus. The
      reactivity of Mabs for rE2 protein was demonstrated using ELISA. The specificity
      of the generated Mabs for rE2 was demonstrated by Western blot and indirect
      immunofluorescence. The application of this CHIK virus E2-specific monoclonal
      antibody in early clinical diagnosis was demonstrated by various analytical
      methods, such as immunoblotting, indirect immunofluorescence assay (IFA), and
      antigen-capture ELISA (AC-ELISA), for the detection as well as the identification
      of the novel ECSA genotypes of CHIK virus. These findings suggest that the high
      affinity E2-specific monoclonal antibodies reported in this study will be useful
      for early clinical diagnosis and epidemiological studies of CHIK virus in
      developing countries.

PMID- 22420757
TI  - Biologics in oral medicine: principles of use and practical considerations.
AB  - Oral Diseases (2012) 18, 525-536 Biologic therapies are relatively innovative
      treatments aimed at modulating lymphocytes or cytokines. There are currently
      three broad classes of biologic therapies, tumour necrosis factor-alpha
      inhibitors, lymphocyte modulators and interleukin inhibitors; all are
      increasingly used in the treatment of inflammatory immune-mediated conditions,
      and several have potential applications in oral medicine. Guidelines for their
      use in licensed indications (e.g. rheumatoid arthritis, psoriasis, inflammatory
      bowel disease) include recommendations and guidance for patient selection and
      subsequent monitoring with discussion of potential adverse effects. An
      understanding of these is important when managing patients receiving biologic
      therapy for systemic disease, and compliance is essential in any use in oral
      medicine. Key aspects of current guidance are presented with particular emphasis
      on their relevance to clinicians working within oral and maxillofacial
      medicine/pathology/surgery and in specialist practice.

PMID- 22420758
TI  - Clinical evaluation of a new tracheal impedance cardiography method.
AB  - Non-invasive cardiac output measurement by means of impedance cardiography has
      been evaluated before, and agreement with other methods has been variable. We
      decided to study a newly developed tracheal impedance device, that is claimed to
      be more accurate and reliable. This incorporates new software and mathematical
      formulae, that are designed to reduce signal noise from diathermy, leading to
      improved accuracy. In 25 cardiothoracic surgery patients, simultaneous
      measurements were performed using both pulmonary artery thermodilution and the
      tracheal impedance device, at five peri-operative time points: before skin
      incision; after weaning from cardiopulmonary bypass; after sternal closure; and
      30 min and 2 h after arrival in the intensive care unit. Mean cardiac output,
      bias and 95% limits of agreement were 5.3, 0.03 and -2.8 to 2.8 l.min(-1) ,
      respectively. Tracheal impedance showed good correlation with measurement trends
      using thermodilution in 88% of measurements, with a mean (95% limit of agreement)
      angular bias of -9.0 degrees  (-83.3 to 65.3 degrees ). However, the wide limits
      of agreement and high percentage error of 53% that were apparent in this study
      mean that, in its present guise, tracheal impedance is not an acceptable
      alternative to thermodilution in cardiac surgical patients.

PMID- 22420759
TI  - The availability of snack food displays that may trigger impulse purchases in
      Melbourne supermarkets.
AB  - BACKGROUND: Supermarkets play a major role in influencing the food purchasing
      behaviours of most households. Snack food exposures within these stores may
      contribute to higher levels of consumption and ultimately to increasing levels of
      obesity, particularly within socioeconomically disadvantaged neighbourhoods. We
      aimed to examine the availability of snack food displays at checkouts, end-of
      aisle displays and island displays in major supermarket chains in the least and
      most socioeconomically disadvantaged neighbourhoods of Melbourne. METHODS: Within
      store audits of 35 Melbourne supermarkets. Supermarkets were sampled from the
      least and most socioeconomically disadvantaged suburbs within 30 km of the
      Melbourne CBD. We measured the availability of crisps, chocolate, confectionery,
      and soft drinks (diet and regular) at the checkouts, in end-of-aisle displays,
      and in island bin displays. RESULTS: Snack food displays were most prominent at
      checkouts with only five stores not having snack foods at 100% of their
      checkouts. Snack foods were also present at a number of end-of-aisle displays (at
      both the front (median 38%) and back (median 33%) of store), and in island bin
      displays (median number of island displays: 7; median total circumference of
      island displays: 19.4 metres). Chocolate items were the most common snack food
      item on display. There was no difference in the availability of these snack food
      displays by neighbourhood disadvantage. CONCLUSIONS: As a result of the high
      availability of snack food displays, exposure to snack foods is almost
      unavoidable in Melbourne supermarkets, regardless of levels of neighbourhood
      socioeconomic disadvantage. Results of this study could promote awareness of the
      prominence of unhealthy food items in chain-brand supermarkets outlets.

PMID- 22420760
TI  - Preterm premature rupture of membranes in the presence of cerclage: is the risk
      for intra-uterine infection and adverse neonatal outcome increased?
AB  - OBJECTIVE: To determine whether preterm premature rupture of membranes (PPROM) in
      the presence of a cerclage is associated with an increased incidence of
      intrauterine infection and/or adverse neonatal outcome compared to PPROM in the
      absence of cerclage. STUDY DESIGN: Patients diagnosed with PPROM with a cerclage
      (cases) between 24-34 weeks were matched (1:2.6) for gestational age at PPROM,
      gestational number, and chorionicity with patients diagnosed with PPROM without a
      cerclage (controls). RESULTS: Pregnancy latency period was not different but the
      rates of chorioamnionitis [clinical (26.6% versus 13.5%) and histological (92.6%
      versus 65.4%)] and the rates of adverse perinatal outcome were higher following
      PPROM in the presence of a cerclage compared with no cerclage. CONCLUSION: The
      presence of a cerclage in patients with PPROM appears to increase the risk of
      intra-uterine infection and affect neonatal outcome; it may not be justified to
      leave a cerclage in place in patients with PPROM.

PMID- 22420761
TI  - Plant proteases - from detection to function.

PMID- 22420762
TI  - Isoquinoline derivatives via stepwise regioselective sp(2) and sp(3) C-H bond
      functionalizations.
AB  - Efficient and practically attractive stepwise ruthenium- and palladium-catalyzed
      regioselective C-H bond functionalizations were achieved to produce 4-substituted
      tetrahydroisoquinoline derivatives featuring various heteroaromatic substructures
      in moderate to good yields. Both ruthenium- and palladium-based catalytic
      processes generated nontoxic and easily separable side products.

PMID- 22420763
TI  - Low-temperature synthesis of amorphous FeP2 and its use as anodes for Li ion
      batteries.
AB  - The reaction of Fe(N(SiMe(3))(2))(3) with PH(3) in THF at 100  degrees C gives
      amorphous FeP(2) in high yield. As an anode material in a Li ion battery, this
      material shows remarkable performance toward electrochemical
      lithiation/delithation, with gravimetric discharge and charge capacities of 1258
      and 766 mA h g(-1), respectively, translating to 61% reversibility on the first
      cycle and a discharge capacity of 906 mA h g(-1) after 10 cycles. This translates
      to 66% retention of the theoretical full conversion capacity of FeP(2) (1365 mA h
      g(-1)).

PMID- 22420764
TI  - Local medial microenvironment directs phenotypic modulation of smooth muscle
      cells after experimental renal transplantation.
AB  - Smooth muscle cells (SMCs) play a key role in the pathogenesis of occlusive
      vascular diseases, including transplant vasculopathy. Neointimal SMCs in
      experimental renal transplant vasculopathy are graft-derived. We propose that
      neointimal SMCs in renal allografts are derived from the vascular media resulting
      from a transplantation-induced phenotypic switch. We examined the molecular
      changes in the medial microenvironment that lead to phenotypic modulation of SMCs
      in rat renal allograft arteries with neointimal lesions. Dark Agouti donor
      kidneys were transplanted into Wistar Furth recipients and recovered at day 56.
      Neointimal and medial layers were isolated using laser microdissection. Gene
      expression was analyzed using low-density arrays and confirmed by immunostaining.
      In allografts, neointimal SMCs expressed increased levels of Tgf beta1 and Pdgfb.
      In medial allograft SMCs, gene expression of Ctgf, Tgf beta1 and Pdgfrb was
      upregulated. Gene expression of Klf4 was upregulated as well, while expression of
      Sm22alpha was downregulated. Finally, PDGF-BB-stimulated phenotypically modulated
      SMCs, as evidenced by reduced contractile function in vitro which was accompanied
      by increased Klf4 and Col1alpha1, and reduced alpha-Sma and Sm22alpha expression.
      In transplant vasculopathy, neointimal PDGF-BB induces phenotypic modulation of
      medial SMCs, through upregulation of KLF4 in the media to contribute to (further)
      expansion of the neointima.

PMID- 22420766
TI  - A new class of purple membrane variants for the construction of highly oriented
      membrane assemblies on the basis of noncovalent interactions.
AB  - Purple membranes (PM) from Halobacterium salinarum have been discussed for
      several technical applications. These ideas started just several years after its
      discovery. The biological function of bacteriorhodopsin (BR), the only protein in
      PM, is the light-driven proton translocation across the membrane thereby
      converting light energy into chemical energy. The astonishing physicochemical
      robustness of this molecular assembly and the ease of its isolation triggered
      ideas for technical uses. All basic molecular functions of BR, that is,
      photochromism, photoelectrism, and proton pumping, are key elements for technical
      applications like optical data processing and data storage, ultrafast light
      detection and processing, and direct utilization of sunlight in adenosine 5'
      triphospate (ATP) generation or seawater desalination. In spite of the efforts of
      several research groups worldwide, which confirmed the proof-of-principle for all
      these potential applications, only the photochromism-based applications have
      reached a technical level. The physical reason for this is that no fixation or
      orientation of the PMs is required. The situation is quite different for
      photoelectrism and proton pumping where the macroscopic orientation of PMs is a
      prerequisite. For proton pumping, in addition, the formation of artificial
      membranes which prevent passive proton leakage is necessary. In this manuscript,
      we describe a new class of PM variants with oppositely charged membrane sides
      which enable an almost 100% orientation on a surface, which is the key element
      for photoelectric applications of BR. As an example, the mutated BR, BR-E234R7,
      was prepared and analyzed. A nearly 100% self-orientation on mica was obtained.

PMID- 22420765
TI  - How could undergraduate education prepare new graduates to be safer prescribers?
AB  - This review examines the extent to which undergraduate prescribing education
      prepares graduates for the complexities of prescribing in the workplace context.
      In order to prescribe safely, it is important for medical students to acquire
      prescribing expertise. We have developed a theoretical model, based on theories
      of expertise development, which acknowledges the inherent complexity of the task
      itself, the social context and the relationship between the two. We have examined
      the empirical evidence on educational interventions for prescribing by reviewing
      the extent to which the interventions acknowledge the different components of our
      theoretical model. Fifteen empirical studies met our inclusion criteria and were
      reviewed in detail. All the studies were conducted between 2002 and 2010, six
      were controlled trials, six were before and after studies and three were
      prospective observational studies. We found that most studies focused on
      improving and evaluating students' knowledge and skills, although they used
      different approaches to doing so. These aspects of prescribing only constitute a
      small part of our theoretical model of prescribing expertise. Other important
      components, such as social context, metacognition and training transfer, were
      neglected. We suggest that educational interventions need to account for the
      integrated nature of learning to prescribe and take a more contextualized
      approach which considers the task as a whole, rather than isolated constituent
      parts. In doing so, prescribing education could equip graduates with the
      necessary expertise to judge and respond to situations, enabling them to
      prescribe safely, or seek the help to do so, in the unpredictable and complex
      context of workplaces.

PMID- 22420767
TI  - Novel 3,6,7-substituted pyrazolopyrimidines as positive allosteric modulators for
      the hydroxycarboxylic acid receptor 2 (GPR109A).
AB  - A number of pyrazolopyrimidines were synthesized and tested for their positive
      allosteric modulation of the HCA(2) receptor (GPR109A). Compound 24, an
      efficacious and potent agonist and allosteric enhancer of nicotinic acid's
      action, was the basis for most other compounds. Interestingly, some of the
      compounds were found to increase the efficacy of the endogenous ligand 3
      hydroxybutyrate and enhance its potency almost 10-fold. This suggests that the
      pyrazolopyrimidines may have therapeutic value when given alone.

PMID- 22420768
TI  - Coordination structures and supramolecular architectures in a cerium(III)
      malonamide solvent extraction system.
AB  - The process chemistry and solution structures investigated in the title system
      bridge the three ostensibly disparate fields of separation sciences, soft matter
      research, and coordination chemistry. We have explored this subject with
      synchrotron radiation research and advanced analyses leading to original insights
      into aggregation phenomena in solvent extraction. Herein we present findings
      showing the coagulation of reverse micelles into wormlike aggregates in organic
      phases (N,N'-dimethyl-N,N'-dibutyltetradecylmalonamide-abbreviated as DMDBTDMA-in
      n-dodecane) obtained by liquid-liquid extraction following contact with acidic
      and neutral aqueous media containing trivalent cerium. The growth of solute
      architectures was shown to prelude phase transition (i.e., the formation of a
      "third phase"). The presence of acid was shown to promote the growth of these
      micellar chains and, therefore, promoted third-phase formation. Acid was also
      shown to hydrate and swell the reverse micelle units, preorganizing them to allow
      for incorporation of cerium, leading to different coordination structures and
      enhanced metal extraction. The approach of linking both the coordination
      environment and supramolecular structures to the process properties of a solvent
      extraction system in a single study provides perspectives that are not available
      from independent, uncorrelated experimentation. Moreover, the analysis of small
      angle X-ray scattering data from a solvent extraction system using the
      generalized indirect Fourier transform method to gain real-space information led
      to insights not otherwise available, showing that micellar assemblies are larger
      and more ordered than previously thought. This multipronged and multidisciplinary
      investigation opens new avenues in the evolving understanding of solute
      architectures in organic phases of practical relevance to solvent extraction and,
      simultaneously, of fundamental relevance to structured fluids and, in particular,
      phase transition phenomena.

PMID- 22420769
TI  - Machine perfusion in clinical trials: "machine vs. solution effects".

PMID- 22420770
TI  - Size exclusion and reversed-phase high-performance liquid chromatography/UV for
      routine control of thermal processing of cows' and donkey milk major proteins.
AB  - Cows' and donkey milks (raw and thermally processed) and respective whey were
      analysed for quantification of major proteins. Two different chromatographic
      approaches, size exclusion (SE-HPLC) and reversed-phase high performance liquid
      chromatography (RP-HPLC) both coupled to UV detection were used. Usefulness of
      these methods for routine control of the effect of thermal processing was
      evaluated. The external standard method was used to calibrate the SE-HPLC and RP
      HPLC systems. Concerning quantification of beta-lactoglobulin (beta-lg), alpha
      lactalbumin (alpha-la), lysozyme (lys), and total casein (cn), no significant
      differences between results obtained by SE-HPLC and by RP-HPLC (t-test, P>0.05)
      were observed for raw milks and whey. Heating of cows' milk promoted aggregation
      of denatured proteins as observed by SE-HPLC, whereas alpha-la and beta-lg from
      donkey milk were stable to thermal processing at 100  degrees C (5 min). Lys was
      quantified in donkey raw milk and whey however, in thermally processed donkey
      milk lys was denatured and could not be quantified by HPLC.

PMID- 22420771
TI  - Association of anxiety and ODD/CD in children with and without ADHD.
AB  - The goal of this study is to examine levels of oppositional defiant disorder
      (ODD) and conduct disorder (CD) in four groups of children: attention
      deficit/hyperactivity disorder (ADHD) only, anxiety only, ADHD and anxiety, and
      controls (i.e., non-ADHD youth). Although children with ADHD exhibit more ODD and
      CD than non-ADHD youth, it is unknown if anxiety is associated with increased or
      decreased ODD and CD in children with ADHD. We examined parent and teacher
      ratings of ODD and CD from the Disruptive Behavior Disorder Rating Scale in 203
      school age children (ages 6-9); 70% were male, and 47% were Caucasian. Children
      were divided into four diagnostic groups based on ADHD and anxiety status from
      the Diagnostic Interview Scale for Children. According to parents, children with
      ADHD and anxiety had the highest levels of ODD/CD, followed by children with ADHD
      only (i.e., without anxiety). Children with anxiety only and controls had lowest
      ODD and CD scores, and these groups did not differ from each other. The same
      patterns were found according to teacher report, except that the anxiety only
      group had significantly lower levels of ODD than non-ADHD controls. Further,
      combined type ADHD youth with anxiety exhibited the highest levels of ODD and CD
      compared to all other groups. Comorbid anxiety may strengthen the association of
      ADHD and ODD/CD, particularly in the combined subtype. We discuss the importance
      of comorbid anxiety to the development of externalizing problems as well as
      potential explanatory factors underlying elevated ODD and CD among children with
      ADHD and anxiety.

PMID- 22420772
TI  - The educational value of using cumulative sum charts.
AB  - Various workplace-based assessment tools are available, but none have been shown
      to improve performance in procedural skills. This study aimed to assess the
      impact of using one such tool, cumulative sum charts, on procedural skill
      ability. A single-blind randomised controlled trial was conducted on 82 final
      year medical students. Control group students received the usual teaching; in
      addition to this, intervention group students were provided with cumulative sum
      charts to log their cannulation attempts over a 7-month period. At the end of the
      year, students from both groups undertook a validated test of automaticity of
      cannulation skill. Students in the intervention group obtained median (IQR
      [range]) scores of 68.2 (60.5-74.3 [42.7-81.1]) vs 62.2 (52.2-68.8 [40.7-80.5])
      for the control group (p = 0.013). The effect size was moderate (Cohen's d =
      0.608). This study therefore provides support for the hypothesis that use of
      cumulative sum charts improves performance when learning procedural skills.

PMID- 22420773
TI  - Prostaglandin E2 maintains mouse ESC undifferentiated state through regulation of
      connexin31, connexin43 and connexin45 expression: involvement of glycogen
      synthase kinase 3beta/beta-catenin.
AB  - BACKGROUND INFORMATION: Although previous reports have examined the function of
      prostaglandin E2 (PGE2) on gap junctions and undifferentiated stem cells, its
      effects on the reciprocal action of connexin (Cx) isoforms and undifferentiation
      in embryonic stem cells (ESCs) are unclear. Therefore, we investigated the role
      of PGE2 on Cx isoforms and maintenance of mouse ESC undifferentiated state.
      RESULTS: We have analysed 10 Cx genes, but found nine of them. PGE2 (50 MUM)
      stimulated Cx31, Cx32, Cx40, Cx43 and Cx45 mRNA expression. Amongst them, PGE2
      maximally stimulated the Cx43 mRNA expression and gap junction inter-cellular
      coupling. Therefore, we investigated the effect of PGE2 on Cx43 expression. PGE2
      activated cAMP/protein kinase A (PKA) and phosphatidylinositol 3-kinase
      (PI3K)/Akt phosphorylation. In addition, treatments of adenylate cyclase
      activators increased Cx43 expression, but not PI3K/Akt phosphorylation. PGE2 also
      inactivated GSK-3beta and stimulated active-beta-catenin. Furthermore, a ChiP
      assay demonstrated the association of beta-catenin with the Cx26 (as control) and
      Cx43 promoter. Finally, down-regulation of PGE2-induced Cx isoforms by AH 6809,
      Cx31-, Cx43-, Cx45 small interfering (si)RNA and 18alpha-glycyrrhetinic acid
      decreased levels of undifferentiated markers of ESCs, including Oct4, FoxD3, Sox2
      and SSEA-1, but Nanog did not be down-regulated by Cx43 siRNA. CONCLUSIONS: PGE2
      stimulates Cx isoforms via GSK-3beta/beta-catenin via EP2-receptor-dependent
      cAMP/PKA and PI3K/Akt in mouse ESCs, thereby partially contributing to the
      maintenance of their undifferentiated state.

PMID- 22420774
TI  - Revisiting sociotechnical systems in a case of unreported use of health
      information exchange system in three hospital emergency departments.
AB  - BACKGROUND: Health information exchange (HIE) allows clinicians to access patient
      level health care information. HIE can potentially improve patient care in
      emergency departments. METHODS: We present a selected piece of evaluation of an
      HIE implementation in three Midwestern emergency departments. Data were collected
      through over 210 hours of direct observations and short interviews with 13
      clinicians. RESULTS: The results suggest that the usage rate of the HIE was low.
      Moreover, two ways of unreported use of the HIE system by clinicians was
      uncovered: (1) The HIE system was being used mostly for patients only with
      specific characteristics. (2) The information from the HIE system could be used
      to confront with the patients. DISCUSSION: This study provides a case of how
      social system may shape a HIE technology. In order to fully benefit from HIE,
      understanding organizational and social context during the HIE design and
      implementation is needed. Such an understanding will also allow us to identify
      and detail required additional resources and organizational interventions that
      will complement HIE such as a case management strategy.

PMID- 22420775
TI  - UVR defense mechanisms in eurytopic and invasive Gracilaria vermiculophylla
      (Gracilariales, Rhodophyta).
AB  - The invasive success of Gracilaria vermiculophylla has been attributed to its
      wide tolerance range to different abiotic factors, but its response to
      ultraviolet radiation (UVR) is yet to be investigated. In the laboratory,
      carpospores and vegetative thalli of an Atlantic population were exposed to
      different radiation treatments consisting of high PAR (photosynthetically active
      radiation) only (P), PAR+UV-A (PA) and PAR+UV-A+UV-B (PAB). Photosynthesis of
      carpospores was photoinhibited under different radiation treatments but
      photosystem II (PSII) function was restored after 12 h under dim white light.
      Growth of vegetative thalli was significantly higher under radiation supplemented
      with UVR. Decrease in chlorophyll a (Chl a) under daily continuous 16-h exposure
      to 300 umol photons m(-2)  s(-1)  of PAR suggests preventive accumulation of
      excited chlorophyll molecules within the antennae to minimize the generation of
      dangerous reactive oxygen species. Moreover, an increase in total carotenoids and
      xanthophyll cycle pigments (i.e. violaxanthin, antheraxanthin and zeaxanthin)
      further suggests effective photoprotection under UVR. The presence of the
      ketocarotenoid beta-cryptoxanthin also indicates protection against UVR and
      oxidative stress. The initial concentration of total mycosporine-like amino acids
      (MAAs) in freshly-released spores increased approximately four times after 8-h
      laboratory radiation treatments. On the other hand, initial specific MAAs in
      vegetative thalli changed in composition after 7-day exposure to laboratory
      radiation conditions without affecting the total concentration. The above
      responses suggest that G. vermiculophylla have multiple UVR defense mechanisms to
      cope with the dynamic variation in light quantity and quality encountered in its
      habitat. Beside being eurytopic, the UVR photoprotective mechanisms likely
      contribute to the current invasive success of the species in shallow lagoons and
      estuaries exposed to high solar radiation.

PMID- 22420776
TI  - Bond strengths of one-step self-etch adhesives to laser-irradiated and bur-cut
      dentin after water storage and thermocycling.
AB  - OBJECTIVE: The objectives of this study were to evaluate the microtensile bond
      strength (MUTBS) of one-step self-etch adhesive systems to Er:YAG laser
      irradiated and bur-cut dentin after water storage and thermocycling. BACKGROUND
      DATA: The Er:YAG laser is a promising alternative method for cavity preparation;
      however, no study has compared the effect of laser irradiation and aging
      procedures on the adhesion of one-step self-etch adhesives to dentin. METHODS:
      Seventy-two third molars were selected and randomly divided according to cavity
      preparation method (Er:YAG laser and bur-cut). One-step self-etch adhesive
      systems (Clearfil S(3) Bond, AdheSE One and Adper Easy One) were used to bond the
      composite to dentin. Following the adhesive procedure, the specimens were
      subdivided according to aging conditions (24 h in water control [C], 6 months of
      water storage [WS] and 10.000 thermocycles [TC]). The MUTBS was determined in a
      universal testing machine. Three-way ANOVA, independent samples t test, and post
      hoc comparisons test (alpha=0.05) were performed on all data. RESULTS: There was
      no statistical difference in MUTBS between Er:YAG laser-irradiated and bur-cut
      dentin (p>0.05). Similarly, no significant difference was found in MUTBS between
      C, WS, and TC specimens (p>0.05). Moreover, Clearfil S(3) Bond presented the
      highest MUTBS to dentin in both laser-irradiated and bur-cut cavity preparation
      methods. CONCLUSIONS: Neither bur-cut nor Er:YAG laser-irradiated dentin was
      affected by the aging methods used to simulate degradation of the adhesive
      interface. Er:YAG laser treatment may be used as an alternative cavity
      preparation method.

PMID- 22420777
TI  - HIV-1 Nef interaction influences the ATP-binding site of the Src-family kinase,
      Hck.
AB  - BACKGROUND: Nef is an HIV-1 accessory protein essential for viral replication and
      AIDS progression. Nef interacts with a multitude of host cell signaling partners,
      including members of the Src kinase family. Nef preferentially activates Hck, a
      Src-family kinase (SFK) strongly expressed in macrophages and other HIV target
      cells, by binding to its regulatory SH3 domain. Recently, we identified a series
      of kinase inhibitors that preferentially inhibit Hck in the presence of Nef.
      These compounds also block Nef-dependent HIV replication, validating the Nef-SFK
      signaling pathway as an antiretroviral drug target. Our findings also suggested
      that by binding to the Hck SH3 domain, Nef indirectly affects the conformation of
      the kinase active site to favor inhibitor association. RESULTS: To test this
      hypothesis, we engineered a "gatekeeper" mutant of Hck with enhanced sensitivity
      to the pyrazolopyrimidine tyrosine kinase inhibitor, NaPP1. We also modified the
      RT loop of the Hck SH3 domain to enhance interaction of the kinase with Nef. This
      modification stabilized Nef:Hck interaction in solution-based kinase assays, as a
      way to mimic the more stable association that likely occurs at cellular
      membranes. Introduction of the modified RT loop rendered Hck remarkably more
      sensitive to activation by Nef, and led to a significant decrease in the Km for
      ATP as well as enhanced inhibitor potency. CONCLUSIONS: These observations
      suggest that stable interaction with Nef may induce Src-family kinase active site
      conformations amenable to selective inhibitor targeting.

PMID- 22420778
TI  - Generation and physiological roles of linear ubiquitin chains.
AB  - Ubiquitination now ranks with phosphorylation as one of the best-studied post
      translational modifications of proteins with broad regulatory roles across all of
      biology. Ubiquitination usually involves the addition of ubiquitin chains to
      target protein molecules, and these may be of eight different types, seven of
      which involve the linkage of one of the seven internal lysine (K) residues in one
      ubiquitin molecule to the carboxy-terminal diglycine of the next. In the eighth,
      the so-called linear ubiquitin chains, the linkage is between the amino-terminal
      amino group of methionine on a ubiquitin that is conjugated with a target protein
      and the carboxy-terminal carboxy group of the incoming ubiquitin. Physiological
      roles are well established for K48-linked chains, which are essential for
      signaling proteasomal degradation of proteins, and for K63-linked chains, which
      play a part in recruitment of DNA repair enzymes, cell signaling and endocytosis.
      We focus here on linear ubiquitin chains, how they are assembled, and how three
      different avenues of research have indicated physiological roles for linear
      ubiquitination in innate and adaptive immunity and suppression of inflammation.

PMID- 22420780
TI  - Scaling movement amplitude: adaptation of timing and amplitude control in a
      bimanual task.
AB  - Participants traced two circles simultaneously and the diameter of one circle was
      scaled as the diameter of the other circle remained constant. When the scaled
      circle was larger, amplitude error shifted from overshooting to undershooting,
      while shifting from undershooting to overshooting when this circle was smaller.
      Asymmetric coordination was unstable when the left arm traced a circle larger
      than the right arm, yet stable when the left arm traced a smaller circle. When
      producing symmetric coordination and the left arm traced the larger circle,
      relative phase shifted by 30 degrees , but a right arm lead predominated. When
      the left arm traced the smaller circle and symmetric coordination was required, a
      30 degrees  shift in relative phase occurred, but hand lead changed from left to
      right. The modulation of movement amplitude and relative phase emerged
      simultaneously as a result of neural crosstalk effects linked to initial
      amplitude conditions and possibly visual feedback of the hands' motion.

PMID- 22420781
TI  - Statistical analysis of RR series variability in spinal cord injured persons.
AB  - Disabled persons with spinal cord injury are prone to cardiovascular dysfunction
      and an increased risk of cardiovascular disease. Rehabilitation of the disabled
      person is a critical task as it involves multiple therapies. Physical exercise is
      an important component of rehabilitation, and depends on cardiovascular health.
      Reduced RR variability is a marker of poor cardiac health. Time domain RR
      variability analysis of 38 normal healthy subjects and 20 spinal cord injured
      subjects has been carried out and compared. In this study, RR intervals were
      recorded in three different modes or positions: supine, sitting and five-second
      rhythm respiration. At a time of 150 s RR interval data were acquired in each
      mode and analysed. Statistical parameters (mean, HR, STD, NN50 and pNN50) were
      calculated. It was observed that most of the indices were significantly and
      substantially altered in spinal cord injured persons.

PMID- 22420779
TI  - The application of selective reaction monitoring confirms dysregulation of
      glycolysis in a preclinical model of schizophrenia.
AB  - BACKGROUND: Establishing preclinical models is essential for novel drug discovery
      in schizophrenia. Most existing models are characterized by abnormalities in
      behavioral readouts, which are informative, but do not necessarily translate to
      the symptoms of the human disease. Therefore, there is a necessity of
      characterizing the preclinical models from a molecular point of view. Selective
      reaction monitoring (SRM) has already shown promise in preclinical and clinical
      studies for multiplex measurement of diagnostic, prognostic and treatment-related
      biomarkers. METHODS: We have established an SRM assay for multiplex analysis of 7
      enzymes of the glycolysis pathway which is already known to be affected in human
      schizophrenia and in the widely-used acute PCP rat model of schizophrenia. The
      selected enzymes were hexokinase 1 (Hk1), aldolase C (Aldoc), triosephosphate
      isomerase (Tpi1), glyceraldehyde-3-phosphate dehydrogenase (Gapdh),
      phosphoglycerate mutase 1 (Pgam1), phosphoglycerate kinase 1 (Pgk1) and enolase 2
      (Eno2). The levels of these enzymes were analyzed using SRM in frontal cortex
      from brain tissue of PCP treated rats. RESULTS: Univariate analyses showed
      statistically significant altered levels of Tpi1 and alteration of Hk1, Aldoc,
      Pgam1 and Gapdh with borderline significance in PCP rats compared to controls.
      Most interestingly, multivariate analysis which considered the levels of all 7
      enzymes simultaneously resulted in generation of a bi-dimensional chart that can
      distinguish the PCP rats from the controls. CONCLUSIONS: This study not only
      supports PCP treated rats as a useful preclinical model of schizophrenia, but it
      also establishes that SRM mass spectrometry could be used in the development of
      multiplex classification tools for complex psychiatric disorders such as
      schizophrenia.

PMID- 22420782
TI  - Negative pressure wound therapy in acute, contaminated wounds: documenting its
      safety and efficacy to support current global practice.
AB  - Negative pressure wound therapy (NPWT) is in widespread use and its role in wound
      care is expanding worldwide. It is estimated that 300 million acute wounds are
      treated globally each year. Currently, sporadic data exist to support NPWT in
      acutely contaminated wounds. Despite lack of data, use of negative pressure wound
      therapy in such cases is increasing across the globe. We retrospectively reviewed
      86 consecutive patients, totalling 97 contaminated wounds. All wounds were Class
      IV based on US Center for Disease Control criteria. Sepsis criteria were present
      in 78/86 (91%) of patients. All patients were managed with NPWT. Wound type,
      degree of tissue destruction, presence of infection, wound dimension, timing of
      initial NPWT, type and timing of wound closure and patient comorbidities were
      recorded. Outcome endpoints included durability of wound closure and death. Wound
      location was 41/97 (42%) in the torso; 56/97 (58%) at the extremities. Tissue
      necrosis was present in 84/97 (87%) of wounds. Infection was present in 86/97
      (89%) of wounds. Average wound size was 619 cm(2)  when square surface area
      measured; 786 cm(3)  when volume measurements taken. Mean time to wound closure
      was 17 days, median 10 days and mode 6 days. Durability of wound closure 73/79
      (92%). Deaths were noted in 6/86 (7%) of patients. No deaths appeared related to
      NPWT. Contemporary NPWT related acute wound care is expanding empirically, in
      quantity and scope across the globe. However, several areas of concern are known
      regarding this contemporary use of NPWT in acute wounds. Thus, it is important to
      assess the safety and efficacy of such expanded empiric NPWT practice. Based on
      our findings with NPWT in the largest known patient cohort of this type, NPWT
      appears safe and effective in managing acute, contaminated wounds including
      patients meeting sepsis criteria. These findings provide evidence-based support
      for current worldwide empiric NPWT-related acute wound care.

PMID- 22420783
TI  - FK506-binding protein 51 interacts with Clostridium botulinum C2 toxin and FK506
      inhibits membrane translocation of the toxin in mammalian cells.
AB  - The binary Clostridium botulinum C2 toxin consists of the binding/translocation
      component C2IIa and the separate enzyme component C2I. C2IIa delivers C2I into
      the cytosol of eukaryotic target cells where C2I ADP-ribosylates actin. After
      receptor-mediated endocytosis of the C2IIa/C2I complex, C2IIa forms pores in
      membranes of acidified early endosomes and unfolded C2I translocates through the
      pores into the cytosol. Membrane translocation of C2I is facilitated by the
      activities of host cell chaperone Hsp90 and the peptidyl-prolyl cis/trans
      isomerase (PPIase) cyclophilin A. Here, we demonstrated that Hsp90 co
      precipitates with C2I from lysates of C2 toxin-treated cells and identified the
      FK506-binding protein (FKBP) 51 as a novel interaction partner of C2I in vitro
      and in intact mammalian cells. Prompted by this finding, we used the specific
      pharmacological inhibitor FK506 to investigate whether the PPIase activity of
      FKBPs plays a role during membrane translocation of C2 toxin. Treatment of cells
      with FK506 protected cultured cells from intoxication with C2 toxin. Moreover,
      FK506 inhibited the pH-dependent translocation of C2I across membranes into the
      cytosol but did not interfere with the enzyme activity of C2I or binding of C2
      toxin to cells. Furthermore, FK506 treatment delayed intoxication with the
      related binary actin ADP-ribosylating toxins from Clostridium perfringens (iota
      toxin) and Clostridium difficile (CDT) but not with the Rho-glucosylating
      Clostridium difficile toxin A (TcdA). In conclusion, our results support the
      hypothesis that clostridial binary actin-ADP-ribosylating toxins share a specific
      FKBP-dependent translocation mechanism during their uptake into mammalian cells.

PMID- 22420784
TI  - Rhodium-catalyzed enantioselective hydrogenation of unsaturated phosphonates by
      ClickFerrophos ligands.
AB  - Newly developed ClickFerrophos II ligands were applied in the hydrogenation of
      alpha,beta-unsaturated phosphonates. The use of a rhodium/ClickFerrophos II
      catalyst was examined in the hydrogenation of functionalized alpha,beta
      unsaturated phosphonates and was revealed to be effective for beta-alkyl-beta
      aryl or beta-dialkyl phosphonates, (Z)-beta-enolester phosphonates, and alpha
      phenylethenyl phosphonates, producing the corresponding chiral phosphonates in
      good yields with high enantioselectivities (up to 96% ee).

PMID- 22420785
TI  - Delivering health information via podcast or web: media effects on psychosocial
      and physiological responses.
AB  - This study explored differences in psychosocial and physiological variables in
      response to being presented with information on weight loss through either
      reading text on a website or listening to the same information via podcast.
      Participants were randomized to receive a weight loss website (n = 20) or podcast
      (n = 20). Participants had skin conductance levels measured and completed
      questionnaire items assessing demographic characteristics, user control, novelty,
      and knowledge. Participants in the podcast group exhibited greater levels of
      physiological arousal and reported the intervention to be more novel than those
      in the Web group; however, the Web group reported greater user control. There was
      no difference in knowledge between the groups. This study presents the first step
      in examining the role that novelty and user control may play in two different
      weight-loss electronic media, as well as differences in knowledge acquisition.
      Future research should explore adding additional media features, such as video
      content, to the podcasts and websites in order to optimize fully the different
      mediums and to examine whether user control and novelty are potential mediators
      of weight loss outcomes.

PMID- 22420786
TI  - Culturally responsive suicide prevention in indigenous communities: unexamined
      assumptions and new possibilities.
AB  - Indigenous communities have significantly higher rates of suicide than non-Native
      communities in North America. Prevention and intervention efforts have failed to
      redress this disparity. One explanation is that these efforts are culturally
      incongruent for Native communities. Four prevalent assumptions that underpin
      professional suicide prevention may conflict with local indigenous understandings
      about suicide. Our experiences in indigenous communities led us to question
      assumptions that are routinely endorsed and promoted in suicide prevention
      programs and interventions. By raising questions about the universal relevance of
      these assumptions, we hope to stimulate exchange and inquiry into the character
      of this devastating public health challenge and to aid the development of
      culturally appropriate interventions in cross-cultural contexts.

PMID- 22420787
TI  - The associations of clinicians' implicit attitudes about race with medical visit
      communication and patient ratings of interpersonal care.
AB  - OBJECTIVES: We examined the associations of clinicians' implicit attitudes about
      race with visit communication and patient ratings of care. METHODS: In a cross
      sectional study of 40 primary care clinicians and 269 patients in urban community
      based practices, we measured clinicians' implicit general race bias and race and
      compliance stereotyping with 2 implicit association tests and related them to
      audiotape measures of visit communication and patient ratings. RESULTS: Among
      Black patients, general race bias was associated with more clinician verbal
      dominance, lower patient positive affect, and poorer ratings of interpersonal
      care; race and compliance stereotyping was associated with longer visits, slower
      speech, less patient centeredness, and poorer ratings of interpersonal care.
      Among White patients, bias was associated with more verbal dominance and better
      ratings of interpersonal care; race and compliance stereotyping was associated
      with less verbal dominance, shorter visits, faster speech, more patient
      centeredness, higher clinician positive affect, and lower ratings of some aspects
      of interpersonal care. CONCLUSIONS: Clinician implicit race bias and race and
      compliance stereotyping are associated with markers of poor visit communication
      and poor ratings of care, particularly among Black patients.

PMID- 22420788
TI  - Climate change and ecosystem disruption: the health impacts of the North American
      Rocky Mountain pine beetle infestation.
AB  - In the United States and Canada, pine forest ecosystems are being dramatically
      affected by an unprecedented pine beetle infestation attributed to climate
      change. Both decreased frequency of extremely cold days and warmer winter
      temperature averages have led to an enphytotic devastating millions of acres of
      pine forest. The associated ecosystem disruption has the potential to cause
      significant health impacts from a range of exposures, including increased runoff
      and water turbidity, forest fires, and loss of ecosystem services. We review
      direct and indirect health impacts and possible prevention strategies. The pine
      beetle infestation highlights the need for public health to adopt an ecological,
      systems-oriented view to anticipate the full range of potential health impacts
      from climate change and facilitate effective planned adaptation.

PMID- 22420789
TI  - An experimental investigation of possible memory biases affecting support for
      racial health care policy.
AB  - OBJECTIVES: We aimed to test the theory that estimates of racial disparities may
      be based on small recalled samples of specific individuals (Black vs White), a
      strategy likely to lead to underestimates of true racial disparities and a
      corresponding opposition to race-focused health care policies. METHODS: We asked
      a sample of White adults to list the first 5 Black and White individuals who came
      to mind, and then measured support for various race-focused health care policies.
      RESULTS: Analyses indicated that the Black individuals recalled by participants
      tended to be more famous and wealthy than their White counterparts. Furthermore,
      the tendency to list wealthier Black individuals predicted opposition to
      progressive racial health care programs. A follow-up study demonstrated that
      support for certain race-focused health care policies could be increased by
      informing Whites of potential memory biases. CONCLUSIONS: The survival and
      success of minority health care policies depend partially on public acceptance.
      Education regarding continuing racial disparities may help to increase support
      for race-focused health care policies.

PMID- 22420791
TI  - Experiences and perceptions of medical discrimination among a multiethnic sample
      of breast cancer patients in the Greater San Francisco Bay Area, California.
AB  - OBJECTIVES: We conducted qualitative interviews with breast cancer survivors to
      identify themes related to institutional, personally mediated, and internalized
      discrimination in the medical setting. METHODS: We conducted 7 focus groups and
      23 one-on-one interviews with a multiethnic sample of breast cancer survivors
      randomly selected from a population-based registry covering the Greater San
      Francisco Bay Area, California. RESULTS: Participants reported experiencing
      different forms of medical discrimination related to class, race, and language.
      Among African Americans, participants reported experiencing internalized
      discrimination and personal or group discrimination discrepancy-perceiving
      discrimination against them as a racial/ethnic group, yet not perceiving or
      discussing personal experiences of discrimination. Among Asian immigrants,
      participants reported experiencing institutional and personally mediated overt
      types of discrimination, including lack of access to quality and readily
      available translation services. Our results also indicated well-established
      coping mechanisms in response to discrimination experiences in both groups.
      CONCLUSIONS: Participants reported experiencing medical discrimination at all 3
      levels, which may have deleterious health effects through the biopsychosocial
      stress pathway and through active coping mechanisms that could lead to delayed-
      or underutilization of the health care system to avoid discrimination.

PMID- 22420792
TI  - Health disparities among children with cleft.
AB  - Oral health-related quality of life (OHRQoL) is a multidimensional construct that
      measures well-being associated with the teeth, mouth, and face. This cross
      sectional study examined OHRQoL, demographic data, and clinical indicators in 839
      treatment-seeking youths with cleft from 6 geographically diverse cleft treatment
      centers. Individuals without health insurance and representing ethnic minorities
      had lower OHRQoL scores on the Child Oral Health Impact Profile and a higher rate
      of surgical recommendations. These findings imply a risk factor for reduced
      OHRQoL and unmet needs among vulnerable youths with clefts.

PMID- 22420794
TI  - Sustainability of public health programs.

PMID- 22420793
TI  - Quality of life of people with HIV/AIDS receiving antiretroviral therapy in Cuba:
      a cross-sectional study of the national population.
AB  - OBJECTIVES: We studied the effect of antiretroviral therapy (ART) on the quality
      of life (QOL) of Cubans with HIV/AIDS. METHODS: We conducted a cross-sectional
      study including administration of the Medical Outcomes Study-HIV Health Survey
      Questionnaire to a representative sample of the 1592 Cubans receiving ART in
      2004. For univariate analyses, we compared mean HIV scale scores. We used
      logistic regression models to estimate the association between role function and
      year of diagnosis, between pain and sex, and between health transition and region
      of diagnosis, with adjustment for demographics, ART regimen, and clinical status.
      RESULTS: There were 354 participants (73 women, 281 men). Scores for all
      functional activities showed means higher than 80 out of 100. Pain interfered
      more in women than in men (73.2 vs 81.9; P = .01). When HIV diagnosis occurred
      after 2001, the probability of experiencing difficulties performing work (odds
      ratio [OR] = 4.42; 95% CI = 1.83, 10.73) and pain (OR = 1.70; 95% CI = 1.01,
      2.88) increased compared with earlier diagnosis. People treated with indinavir
      showed a greater perception of general health (58.9 vs 52.4; P = .045) and
      greater health improvement (78.6 vs 67.8; P = .002). CONCLUSIONS: Although Cubans
      receiving ART are maintaining a high QOL, we observed significant differences by
      sex and time of diagnosis. QOL assessment can serve as a health outcome and may
      allow identification of QOL reductions potentially related to ART side effects.

PMID- 22420795
TI  - How the continuity of care document can advance medical research and public
      health.
AB  - Electronic health records in the United States currently isolate digital
      information in proprietary, institutional databases. Experts have identified
      inadequate data exchange as a leading challenge to advancements in care quality
      and efficiency.  Recent federal health information technology incentives adopt an
      extensible standard, called the Continuity of Care Document (CCD), as a new basis
      for digital interoperability. Although this instrument was designed for
      individual provider communications, the CCD can be effectively reused for
      population-based research and public health.  Three examples in this commentary
      demonstrate the potential of CCD aggregation and highlight required changes to
      existing public health and research practices. Transitioning to the use of this
      new interoperability standard should be a priority for public health investment,
      research, and development.

PMID- 22420796
TI  - Pharmaceutical companies' role in state vaccination policymaking: the case of
      human papillomavirus vaccination.
AB  - OBJECTIVES: We sought to investigate roles that Merck & Co Inc played in state
      human papillomavirus (HPV) immunization policymaking, to elicit key stakeholders'
      perceptions of the appropriateness of these activities, and to explore
      implications for relationships between health policymakers and industry. METHODS:
      We used a series of state case studies combining data from key informant
      interviews with analysis of media reports and archival materials. We interviewed
      73 key informants in 6 states that were actively engaged in HPV vaccine policy
      deliberations. RESULTS: Merck promoted school-entry mandate legislation by
      serving as an information resource, lobbying legislators, drafting legislation,
      mobilizing female legislators and physician organizations, conducting consumer
      marketing campaigns, and filling gaps in access to the vaccine. Legislators
      relied heavily on Merck for scientific information. Most stakeholders found
      lobbying by vaccine manufacturers acceptable in principle, but perceived that
      Merck had acted too aggressively and nontransparently in this case. CONCLUSIONS:
      Although policymakers acknowledge the utility of manufacturers' involvement in
      vaccination policymaking, industry lobbying that is overly aggressive, not fully
      transparent, or not divorced from financial contributions to lawmakers risks
      undermining the prospects for legislation to foster uptake of new vaccines.

PMID- 22420797
TI  - A framework for mobilizing communities to advance local tobacco control policy:
      the Los Angeles County experience.
AB  - The Los Angeles County Tobacco Control and Prevention Program was significantly
      restructured in 2004 to improve capacity for local policy adoption. Restructuring
      included creating a fully staffed and trained policy unit; partnering with state
      funded tobacco control organizations to provide high-quality, continuous
      technical assistance and training; implementing a highly structured policy
      adoption approach; expanding community capacity building; and establishing local
      coalitions to mobilize communities. Over the ensuing 6 years (2004-2010), 97
      tobacco control policies were enacted in the county's 88 cities and
      unincorporated area, including 79 that were attributable to the program. By
      comparison, only 15 policies were enacted from 1998 to 2003. Expanding policy
      adoption capacity through program restructuring may be achievable in other local
      jurisdictions.

PMID- 22420798
TI  - Research on discrimination and health: an exploratory study of unresolved
      conceptual and measurement issues.
AB  - OBJECTIVES: Our goal in this study was to better understand racial and
      socioeconomic status (SES) variations in experiences of racial and nonracial
      discrimination. METHODS: We used 1999 and 2000 data from the YES Health Study,
      which involved a community sample of 50 Black and 50 White respondents drawn from
      4 neighborhoods categorized according to racial group (majority Black or majority
      White) and SES (<= 150% or > 250% of the poverty line). Qualitative and
      quantitative analyses examined experiences of discrimination across these
      neighborhoods. RESULTS: More than 90% of Blacks and Whites described the meaning
      of unfair treatment in terms of injustice and felt certain about the attribution
      of their experiences of discrimination. These experiences triggered similar
      emotional reactions (most frequently anger and frustration) and levels of stress
      across groups, and low-SES Blacks and Whites reported higher levels of
      discrimination than their moderate-SES counterparts. CONCLUSIONS: Experiences of
      discrimination were commonplace and linked to similar emotional responses and
      levels of stress among both Blacks and Whites of low and moderate SES. Effects
      were the same whether experiences were attributed to race or to other reasons.

PMID- 22420800
TI  - Mapping cumulative environmental effects, social vulnerability, and health in the
      San Joaquin Valley, California.
AB  - To understand the social distribution of environmental hazards, methods to assess
      cumulative effects and their health implications are needed. We developed a
      cumulative environmental hazard index integrating environmental data on pollution
      sites, air quality, and pesticide use; a social vulnerability index to measure
      residents' resources to prevent or mitigate health effects; and a health index.
      We found that communities in California's San Joaquin Valley with high social
      vulnerability face more environmental burdens and have worse health conditions.

PMID- 22420801
TI  - Explaining racial/ethnic disparities in children's dental health: a decomposition
      analysis.
AB  - OBJECTIVES: We measured racial/ethnic inequalities in US children's dental health
      and quantified the contribution of conceptually relevant factors. METHODS: Using
      data from the 2007 National Survey of Children's Health, we investigated
      racial/ethnic disparities in selected child dental health and preventive care
      outcomes. We employed a decomposition model to quantify demographic,
      socioeconomic, maternal health, health insurance, neighborhood, and geographic
      effects. RESULTS: Hispanic children had the poorest dental health and lowest
      preventive dental care utilization, followed by Black then White children. The
      model explanatory variables accounted for 58% to 77% of the disparities in dental
      health and 89% to 100% of the disparities in preventive dental care.
      Socioeconomic status accounted for 71% of the gap in preventive dental care
      between Black children and White children and 55% of that between Hispanic
      children and White children. Maternal health, age, and marital status;
      neighborhood safety and social capital; and state of residence were relevant
      factors. CONCLUSIONS: Reducing US children's racial/ethnic dental health
      disparities-which are mostly socioeconomically driven-requires policies that
      recognize the multilevel pathways underlying them and the need for household- and
      neighborhood-level interventions.

PMID- 22420802
TI  - A life course perspective on how racism may be related to health inequities.
AB  - Recent studies show that racism may influence health inequities. As individuals
      grow from infancy into old age, they encounter social institutions that may
      create new exposures to racial bias. Yet, few studies have considered this idea
      fully. We suggest a framework that shows how racism and health inequities may be
      viewed from a life course perspective. It applies the ideas of age-patterned
      exposures, sensitive periods, linked lives, latency period, stress proliferation,
      historic period, and cohorts. It suggests an overarching idea that racism can
      structure one's time in asset-building contexts (e.g., education) or
      disadvantaged contexts (e.g., prison). This variation in time and exposure can
      contribute to racial inequities in life expectancy and other health outcomes
      across the life course and over generations.

PMID- 22420803
TI  - Methods for the scientific study of discrimination and health: an ecosocial
      approach.
AB  - The scientific study of how discrimination harms health requires theoretically
      grounded methods. At issue is how discrimination, as one form of societal
      injustice, becomes embodied inequality and is manifested as health inequities. As
      clarified by ecosocial theory, methods must address the lived realities of
      discrimination as an exploitative and oppressive societal phenomenon operating at
      multiple levels and involving myriad pathways across both the life course and
      historical generations. An integrated embodied research approach hence must
      consider (1) the structural level-past and present de jure and de facto
      discrimination; (2) the individual level-issues of domains, nativity, and use of
      both explicit and implicit discrimination measures; and (3) how current research
      methods likely underestimate the impact of racism on health.

PMID- 22420804
TI  - A physician's perspective on health care discrimination.

PMID- 22420805
TI  - The lived experience of race and its health consequences.
AB  - A growing body of research illuminates the mechanisms through which racism and
      discrimination influence the health status of people of color. Much of the focus
      of this research, however, has been on individually mediated racism (i.e., acts
      of discrimination and racial bias committed by White individuals against people
      of color).  Yet research literature provides numerous examples of how racism
      operates not just at individual levels, but also at internalized, institutional,
      and structural levels. A more comprehensive model of the lived experience of race
      is needed that considers the cumulative, interactive effects of different forms
      of racism on health over the lifespan.  Such a model must facilitate an
      intersectional analysis to better understand the interaction of race with gender,
      socioeconomic status, geography, and other factors, and should consider the
      negative consequences of racism for Whites.

PMID- 22420806
TI  - Reporting guidelines and the American Journal of Public Health's adoption of
      Preferred Reporting Items for Systematic reviews and Meta-Analyses.
AB  - Widespread recognition of the need to improve the science of published research,
      as well as the moral and ethical reasons for adequately reporting study results,
      has spurred recent interest in strengthening journal research reporting through
      the use of reporting guidelines. Reporting guidelines also provide information
      for readers to judge study quality.  American Journal of Public Health previously
      adopted the Consolidated Standards of Reporting Trials and Transparent Reporting
      of Evaluations With Nonrandomized Designs guidelines and recently endorsed the
      Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. 
      In adopting these guidelines, the journal aims to support authors, reviewers, and
      editors in reporting and evaluating systematic reviews of public health policy
      and practice priorities.

PMID- 22420807
TI  - Perceived discrimination and longitudinal increases in adolescent substance use:
      gender differences and mediational pathways.
AB  - OBJECTIVES: This study was designed to test hypotheses about the prospective
      association of adolescents' perceptions of discrimination with increases in
      substance use and the processes that mediate this association. METHODS: African
      American youths residing in rural Georgia (n = 573; mean age = 16.0 years)
      provided longitudinal data on their experiences with discrimination, substance
      use, school engagement, and affiliations with substance-using peers. RESULTS: For
      male youths, perceived discrimination was significantly related to increases in
      substance use, and, as hypothesized, this association was mediated by the
      contributions of perceived discrimination to decreases in school engagement and
      increases in affiliations with substance-using peers. Analyses also indicated
      that discrimination influences substance use rather than vice versa. CONCLUSIONS:
      Results are consistent with the hypothesis that high levels of discrimination are
      linked to increases in substance use for African American male adolescents.

PMID- 22420808
TI  - Evidence of human papillomavirus vaccine effectiveness in reducing genital warts:
      an analysis of California public family planning administrative claims data, 2007
      2010.
AB  - Because of the rapid development of genital warts (GW) after infection,
      monitoring GW trends may provide early evidence of population-level human
      papillomavirus (HPV) vaccine effectiveness. Trends in GW diagnoses were assessed
      using public family planning administrative data. Between 2007 and 2010, among
      females younger than 21 years, these diagnoses decreased 35% from 0.94% to 0.61%
      (P(trend) < .001). Decreases were also observed among males younger than 21 years
      (19%); and among females and males ages 21-25 (10% and 11%, respectively). The
      diagnoses stabilized or increased among older age groups. HPV vaccine may be
      preventing GW among young people.

PMID- 22420809
TI  - Under the radar: how unexamined biases in decision-making processes in clinical
      interactions can contribute to health care disparities.
AB  - Several aspects of social psychological science shed light on how unexamined
      racial/ethnic biases contribute to health care disparities. Biases are complex
      but systematic, differing by racial/ethnic group and not limited to love-hate
      polarities. Group images on the universal social cognitive dimensions of
      competence and warmth determine the content of each group's overall stereotype,
      distinct emotional prejudices (pity, envy, disgust, pride), and discriminatory
      tendencies. These biases are often unconscious and occur despite the best
      intentions. Such ambivalent and automatic biases can influence medical decisions
      and interactions, systematically producing discrimination in health care and
      ultimately disparities in health. Understanding how these processes may
      contribute to bias in health care can help guide interventions to address racial
      and ethnic disparities in health.

PMID- 22420810
TI  - Life after the ban: an assessment of US syringe exchange programs' attitudes
      about and early experiences with federal funding.
AB  - OBJECTIVES: We aimed to determine whether syringe exchange programs (SEPs)
      currently receive or anticipate pursuing federal funding and barriers to funding
      applications following the recent removal of the long-standing ban on using
      federal funds for SEPs. METHODS: We conducted a telephone-administered cross
      sectional survey of US SEPs. Descriptive statistics summarized responses;
      bivariate analyses examined differences in pursuing funding and experiencing
      barriers by program characteristics. RESULTS: Of the 187 SEPs (92.1%) that
      responded, 90.9% were legally authorized. Three received federal funds and 116
      intended to pursue federal funding. Perceived federal funding barriers were
      common and included availability and accessibility of funds, legal requirements
      such as written police support, resource capacity to apply and comply with
      funding regulations, local political and structural organization, and concern
      around altering program culture. Programs without legal authorization, health
      department affiliation, large distribution, or comprehensive planning reported
      more federal funding barriers. CONCLUSIONS: Policy implementation gaps appear to
      render federal support primarily symbolic. In practice, funding opportunities may
      not be available to all SEPs. Increased technical assistance and legal reform
      could improve access to federal funds, especially for SEPs with smaller capacity
      and tenuous local support.

PMID- 22420811
TI  - Self-reported experience of racial discrimination and health care use in New
      Zealand: results from the 2006/07 New Zealand Health Survey.
AB  - OBJECTIVES: We investigated whether reported experience of racial discrimination
      in health care and in other domains was associated with cancer screening and
      negative health care experiences. METHODS: We used 2006/07 New Zealand Health
      Survey data (n = 12 488 adults). We used logistic regression to examine the
      relationship of reported experience of racial discrimination in health care
      (unfair treatment by a health professional) and in other domains (personal
      attack, unfair treatment in work and when gaining housing) to breast and cervical
      cancer screening and negative patient experiences adjusted for other variables.
      RESULTS: Racial discrimination by a health professional was associated with lower
      odds of breast (odds ratio [OR] = 0.37; 95% confidence interval [CI] = 0.14,
      0.996) and cervical cancer (OR = 0.51; 95% CI = 0.30, 0.87) screening among Maori
      women. Racial discrimination by a health professional (OR = 1.57; 95% CI = 1.15,
      2.14) and racial discrimination more widely (OR = 1.55; 95% CI = 1.35, 1.79) were
      associated with negative patient experiences for all participants. CONCLUSIONS:
      Experience of racial discrimination in both health care and other settings may
      influence health care use and experiences of care and is a potential pathway to
      poor health.

PMID- 22420812
TI  - Regarding Joe Camel in a bottle.

PMID- 22420813
TI  - Strong tobacco control program requirements and secure funding are not enough:
      lessons from Florida.
AB  - Florida's Tobacco Pilot Program (TPP; 1998-2003), with its edgy Truth media
      campaign, achieved unprecedented youth smoking reductions and became a model for
      tobacco control programming. In 2006, 3 years after the TPP was defunded, public
      health groups restored funding for tobacco control programming by convincing
      Florida voters to amend their constitution. Despite the new program's strong
      legal structure, Governor Charlie Crist's Department of Health implemented a low
      impact program. Although they secured the program's strong structure and funding,
      Florida's nongovernmental public health organizations did not mobilize to demand
      a high-impact program. Implementation of Florida's Amendment 4 demonstrates that
      a strong programmatic structure and secure funding are insufficient to ensure a
      successful public health program, without external pressure from nongovernmental
      groups.

PMID- 22420814
TI  - The New York policy on smoking in addiction treatment: findings after 1 year.
AB  - OBJECTIVES: We assessed changes in smoking prevalence and other measures
      associated with the July 2008 New York Office of Alcoholism and Substance Abuse
      Services tobacco policy, which required that all publicly funded addiction
      treatment programs implement smoke-free grounds, have "no evidence" of smoking
      among staff, and make tobacco dependence treatment available for all clients.
      METHODS: In a random sample of 10 programs, staff and clients were surveyed
      before the policy and 1 year later. Measures included tobacco-related knowledge,
      attitudes, and practices used by counselors and received by clients. RESULTS:
      Client smoking decreased from 69.4% to 62.8% (P = .044). However, response to the
      policy differed by program type. Outpatient programs showed no significant
      changes on any of the staff and client survey measures. In methadone programs,
      staff use of tobacco-related practices increased (P < .01), client attitudes
      toward tobacco treatment grew more positive (P < .05), and clients received more
      tobacco-related services (P < .05). Residential clients were more likely to
      report having quit smoking after policy implementation (odds ratio = 4.7; 95%
      confidence interval = 1.53, 14.19), but they reported less favorable attitudes
      toward tobacco treatment (P < .001) and received fewer tobacco-related services
      from their program (P < .001) or their counselor (P < .001). CONCLUSIONS: If
      supported by additional research, the New York policy may offer a model that
      addiction treatment systems can use to address smoking in a population where it
      has been prevalent and intractable. Additional intervention or policy supports
      may be needed in residential programs, which face greater challenges to
      implementing tobacco-free grounds.

PMID- 22420815
TI  - Implicit stereotyping and medical decisions: unconscious stereotype activation in
      practitioners' thoughts about African Americans.
AB  - OBJECTIVES: We investigated whether stereotypes unconsciously influence the
      thinking and behavior of physicians, as they have been shown to do in other
      professional settings, such as among law enforcement personnel and teachers.
      METHODS: We conducted 2 studies to examine whether stereotypes are implicitly
      activated in physicians. Study 1 assessed what diseases and treatments doctors
      associate with African Americans. Study 2 presented these (and control terms) to
      doctors as part of a computerized task. Subliminal images of African American and
      White men appeared prior to each word, and reaction times to words were recorded.
      RESULTS: When primed with an African American face, doctors reacted more quickly
      for stereotypical diseases, indicating an implicit association of certain
      diseases with African Americans. These comprised not only diseases African
      Americans are genetically predisposed to, but also conditions and social
      behaviors with no biological association (e.g., obesity, drug abuse).
      CONCLUSIONS: We found implicit stereotyping among physicians; faces they never
      consciously saw altered performance. This suggests that diagnoses and treatment
      of African American patients may be biased, even in the absence of the
      practitioner's intent or awareness.

PMID- 22420816
TI  - Payer status, race/ethnicity, and acceptance of free routine opt-out rapid HIV
      screening among emergency department patients.
AB  - OBJECTIVES: We estimated associations between payer status, race/ethnicity, and
      acceptance of nontargeted opt-out rapid HIV screening in the emergency department
      (ED). METHODS: We analyzed data from a prospective clinical trial between 2007
      and 2009 at Denver Health. Patients in the ED were offered free HIV testing.
      Patient demographics and payer status were collected, and we used multivariable
      logistic regression to estimate associations with HIV testing acceptance.
      RESULTS: A total of 31,525 patients made 44, 765 unique visits: 40% were White,
      37% Hispanic, 14% Black, 1% Asian, and 7% unknown race/ethnicity. Of all visits,
      10 ,237 (23%) agreed to HIV testing; 27% were self-pay, 23% state-sponsored, 18%
      Medicaid, 13% commercial insurance, 12% Medicare, and 8% another payer source.
      Compared with commercial insurance patients, self-pay patients (odds ratio [OR] =
      1.63; 95% confidence interval [CI] = 1.51, 1.75), state-sponsored patients (OR =
      1.64; 95% CI = 1.52, 1.77), and Medicaid patients (OR = 1.24; 95% CI = 1.14,
      1.34) had increased odds of accepting testing. Compared with White patients,
      Black (OR = 1.29; 95% CI = 1.21, 1.38) and Hispanic (OR = 1.17; 95% CI = 1.11,
      1.23) patients had increased odds of accepting testing. CONCLUSIONS: Many ED
      patients are uninsured or subsidized through government programs and are more
      likely to consent to free rapid HIV testing.

PMID- 22420817
TI  - The influence of implicit bias on treatment recommendations for 4 common
      pediatric conditions: pain, urinary tract infection, attention deficit
      hyperactivity disorder, and asthma.
AB  - OBJECTIVES: We examined the association between pediatricians' attitudes about
      race and treatment recommendations by patients' race. METHODS: We conducted an
      online survey of academic pediatricians (n = 86). We used 3 Implicit Association
      Tests to measure implicit attitudes and stereotypes about race. Dependent
      variables were recommendations for pain management, urinary tract infections,
      attention deficit hyperactivity disorder, and asthma, measured by case vignettes.
      We used correlational analysis to assess associations among measures and
      hierarchical multiple regression to measure the interactive effect of the
      attitude measures and patients' race on treatment recommendations. RESULTS:
      Pediatricians' implicit (unconscious) attitudes and stereotypes were associated
      with treatment recommendations. The association between unconscious bias and
      patient's race was statistically significant for prescribing a narcotic
      medication for pain following surgery. As pediatricians' implicit pro-White bias
      increased, prescribing narcotic medication decreased for African American
      patients but not for the White patients. Self-reported attitudes about race were
      associated with some treatment recommendations. CONCLUSIONS: Pediatricians'
      implicit attitudes about race affect pain management. There is a need to better
      understand the influence of physicians' unconscious beliefs about race on pain
      and other areas of care.

PMID- 22420818
TI  - Discrimination and the stress response: psychological and physiological
      consequences of anticipating prejudice in interethnic interactions.
AB  - OBJECTIVES: We sought to demonstrate that individuals who anticipate interacting
      with a prejudiced cross-race/ethnicity partner show an exacerbated stress
      response, as measured through both self-report and hemodynamic and vascular
      responses, compared with individuals anticipating interacting with a
      nonprejudiced cross-race/ethnicity partner. METHODS: Through a questionnaire
      exchange with a White interaction partner (a confederate) Latina participants
      learned that their partner had racial/ethnic biased or egalitarian attitudes.
      Latina participants reported their cognitive and emotional states, and
      cardiovascular responses were measured while participants prepared and delivered
      a speech to the White confederate. RESULTS: Participants who believed that their
      interaction partner held prejudiced attitudes reported greater concern and more
      threat emotions before the interaction, and more stress after the interaction,
      and showed greater cardiovascular response than did participants who believed
      that their partner had egalitarian attitudes. CONCLUSIONS: This study shows that
      merely anticipating prejudice leads to both psychological and cardiovascular
      stress responses. These results are consistent with the conceptualization of
      anticipated discrimination as a stressor and suggest that vigilance for prejudice
      may be a contributing factor to racial/ethnic health disparities in the United
      States.

PMID- 22420819
TI  - Implementing childhood obesity policy in a new educational environment: the cases
      of Mississippi and Tennessee.
AB  - OBJECTIVES: Our purpose was to investigate the processes involved in, and
      outcomes of, implementing 3 new state-level, school-oriented childhood obesity
      policies enacted between 2004 and 2007. METHODS: We followed policy
      implementation in 8 high schools in Mississippi and Tennessee. We collected data
      between 2006 and 2009 from interviews with policymakers, administrators,
      teachers, and students; observations of school-based activities; and documents.
      RESULTS: Significant barriers to the effective implementation of obesity-related
      policies emerged. These most notably include a value system that prioritizes
      performances in standardized tests over physical education (PE) and a varsity
      sport system that negatively influences opportunities for PE. These and other
      factors, such as resource constraints and the overloading of school
      administrators with new policies, mitigate against the implementation of policies
      designed to promote improvements in student health through PE. CONCLUSIONS:
      Policies designed to address health and social problems in high-school settings
      face significant barriers to effective implementation. To have a broad impact,
      obesity-related policies must be tied to mainstream educational initiatives that
      both incentivize, and hold accountable, the school-level actors responsible for
      their implementation.

PMID- 22420820
TI  - Institutional variation in the promotion of racial/ethnic minority faculty at US
      medical schools.
AB  - OBJECTIVES: We compared faculty promotion rates by race/ethnicity across US
      academic medical centers. METHODS: We used the Association of American Medical
      College's 1983 through 2000 faculty roster data to estimate median institution
      specific promotion rates for assistant professor to associate professor and for
      associate professor to full professor. In unadjusted analyses, we compared
      medians for Hispanic and Black with White faculty using the Wilcoxon rank sum
      test. We compared institution-specific promotion rates between racial/ethnic
      groups with data stratified by institutional characteristic (institution size,
      proportion racial/ethnic minority faculty, and proportion women faculty) using
      the chi(2) test. Our sample included 128 academic medical centers and 88, 432
      unique faculty. RESULTS: The median institution-specific promotion rates for
      White, Hispanic, and Black faculty, respectively, were 30.2%, 23.5%, and 18.8% (P
      < .01) from assistant to associate professor and 31.5%, 25.0%, and 16.7% (P <
      .01) from associate to full professor. CONCLUSIONS: At most academic medical
      centers, promotion rates for Hispanic and Black were lower than those for White
      faculty. Equitable faculty promotion rates may reflect institutional climates
      that support the successful development of racial/ethnic minority trainees,
      ultimately improving healthcare access and quality for all patients.

PMID- 22420821
TI  - Perceived discrimination, psychological distress, and current smoking status:
      results from the Behavioral Risk Factor Surveillance System Reactions to Race
      module, 2004-2008.
AB  - OBJECTIVES: We examined the association between perceived discrimination and
      smoking status and whether psychological distress mediated this relationship in a
      large, multiethnic sample. METHODS: We used 2004 through 2008 data from the
      Behavioral Risk Factor Surveillance System Reactions to Race module to conduct
      multivariate logistic regression analyses and tests of mediation examining
      associations between perceived discrimination in health care and workplace
      settings, psychological distress, and current smoking status. RESULTS: Regardless
      of race/ethnicity, perceived discrimination was associated with increased odds of
      current smoking. Psychological distress was also a significant mediator of the
      discrimination-smoking association. CONCLUSIONS: Our results indicate that
      individuals who report discriminatory treatment in multiple domains may be more
      likely to smoke, in part, because of the psychological distress associated with
      such treatment.

PMID- 22420822
TI  - Lactation weight loss in primiparous sows: consequences for embryo survival and
      progesterone and relations with metabolic profiles.
AB  - Our objective was to study reproductive consequences of lactation bodyweight loss
      occurring in primiparous sows with mild feed restriction and to relate these
      lactation weight losses and its consequences to metabolic profiles during
      lactation and subsequent early gestation. After weaning, 47 first-litter sows
      were retrospectively assigned to a high- (HWL, >13.8%, n= 24) or low (LWL,
      <=13.8%, n = 23)-weight loss group. Thirty-six animals received an indwelling
      jugular vein catheter to determine lactational and gestational profiles of
      insulin-like growth factor-1 (IGF-1), non-esterified fatty acids (NEFA) and urea
      and gestational profiles of progesterone. At day 35 after insemination, sows were
      euthanized and their reproductive tract collected. Pregnancy rate was 75% (18/24)
      for HWL and 96% (22/23) for LWL sows. High-weight loss sows had a lower number of
      implantation sites (17.2 +/- 0.8 vs 19.5 +/- 0.7, respectively, p = 0.03) and a
      lower embryonic survival (65.6 +/- 3.4 vs 77.4 +/- 2.9%, p = 0.02), resulting in
      fewer vital embryos (14.9 +/- 0.9 vs 16.8 +/- 0.7, p = 0.07) than LWL sows.
      Progesterone peak values were reached later in HWL than in LWL sows (day 13.4 +/-
      0.5 vs 12.0 +/- 0.5, respectively, p = 0.05). Gestational concentrations of IGF
      1, NEFA and urea were almost identical for HWL and LWL sows, whilst numerical
      differences were seen during lactation. The current study shows negative
      consequences of lactational weight loss in mildly feed-restricted primiparous
      sows for embryonic survival and shows that these consequences seem only mildly
      related with metabolic alterations during lactation and not with metabolic
      alterations during subsequent gestation.

PMID- 22420823
TI  - Comparison of C4d detection on erythrocytes and PTC-C4d to histological signs of
      antibody-mediated rejection in kidney transplantation.
AB  - C4d on erythrocytes (EC4d), C4d peritubular capillary deposition (PTC-C4d)
      staining and histology were compared in a cross-sectional cohort of 146 renal
      allograft biopsies (132 patients). EC4d levels paralleled PTC-C4d staining, but
      were more predictive of peritubular capillaritis (PTC). Donor-specific antibodies
      (DSA), PTC-C4d, EC4d and PTC were analyzed in an independent longitudinal follow
      up cohort (96 biopsies, 76 patients). Seventy-six samples were PTC and EC4d
      concordant, 11 positive and 65 negative, 7 PTC-EC4d+ and 13 PTC+EC4d-. EC4d
      levels were related to DSA occurrence. With ABMR defined by PTC and DSA, all
      apparently discordant patients, EC4d negative, were correctly reassigned
      comparing EC4d level curves with rejection kinetics, with positive EC4d samples
      predating biopsy or late biopsies compared with ABMR flare-ups. All EC4d-positive
      patients without PTC or DSA had permanent high EC4d levels unrelated to
      rejection. EC4d was more abundant in PTC-positive (mean = 108.5%+/- 3.4; n = 50)
      than PTC-negative samples (mean = 88.1%+/- 1.3; n= 96; p < 0.0001). Sensitivity,
      specificity, positive predictive value and negative predictive value of PTC-C4d
      and EC4d for PTC were, respectively, 75%, 79%; 64%, 76% (p < 0.05); 28%, 46% (p <
      0.05) and 93%, 94%. Values were similar for DSA. A noninvasive blood test, EC4d,
      and particularly longitudinally monitoring EC4d levels, may increase surrogate
      ABMR testing options.

PMID- 22420824
TI  - Effect of the dielectric constant of the surrounding medium and the substrate on
      the surface plasmon resonance spectrum and sensitivity factors of highly
      symmetric systems: silver nanocubes.
AB  - Silver nanocubes (AgNCs), 60 nm, have four extinction surface plasmon resonance
      (SPR) peaks. The finite difference time domain (FDTD) simulation method is used
      to assign the absorption and scattering peaks and also to calculate the plasmon
      field intensity for AgNCs. Because AgNCs have a highly symmetric cubic shape,
      there is a uniform distribution of the plasmon field around them, and they are
      thus sensitive to asymmetric dielectric perturbations. When the dielectric medium
      around a nanoparticle is changed anisotropically, either by placing the particle
      on a substrate or by coating it asymmetrically with a solvent, the plasmon field
      is distorted, and the plasmonic absorption and scattering spectra could shift
      differently. For the 60 nm AgNC, we found that the scattering resonance peak
      shifted more than the absorption peak. This changes the extinction bandwidth of
      these overlapping absorption and scattering bands, and consequently the figure of
      merit of the nanoparticle, as a localized SPR sensor, no longer has a constant
      value.

PMID- 22420825
TI  - Calculation of partition functions and free energies of a binary mixture using
      the energy partitioning method: application to carbon dioxide and methane.
AB  - It is challenging to compute the partition function (Q) for systems with enormous
      configurational spaces, such as fluids. Recently, we developed a Monte Carlo
      technique (an energy partitioning method) for computing Q [  J. Chem. Phys.    
      2011  ,   135  ,   174105  ]. In this paper, we use this approach to compute the
      partition function of a binary fluid mixture (carbon dioxide + methane); this
      allows us to obtain the Helmholtz free energy (F) via F = -k(B)T ln Q and the
      Gibbs free energy (G) via G = F + pV. We then utilize G to obtain the coexisting
      mole fraction curves. The chemical potential of each species is also obtained. At
      the vapor-liquid equilibrium condition, the chemical potential of methane
      significantly increases, while that of carbon dioxide slightly decreases, as the
      pressure increases along an isotherm. Since Q is obtained from the density of
      states, which is independent of the temperature, equilibrium thermodynamic
      properties at any condition can be obtained by varying the total composition and
      volume of the system. Our methodology can be adapted to explore the free energies
      of other binary mixtures in general and of those containing CO(2) in particular.
      Since the method gives access to the free energy and chemical potentials, it will
      be useful in many other applications.

PMID- 22420827
TI  - Multifunctional mercapto-tacrine derivatives for treatment of age-related
      neurodegenerative diseases.
AB  - Cooperating mercapto groups with tacrine in a single molecular, novel
      multifunctional compounds have been designed and synthesized. These mercapto
      tacrine derivatives displayed a synergistic pharmacological profile of long-term
      potentiation enhancement, cholinesterase inhibition, neuroprotection, and less
      hepatotoxicity, emerging as promising molecules for the therapy of age-related
      neurodegenerative diseases.

PMID- 22420828
TI  - Preparation of N2/CO2 triggered reversibly coagulatable and redispersible latexes
      by emulsion polymerization of styrene with a reactive switchable surfactant.
AB  - This work reports the development of a reversibly coagulatable and redispersible
      polystyrene latex system that can be triggered by N(2)/CO(2). The coagulatability
      and redispersibility of the latexes were achieved by employing 0.9-5.6 wt % (N
      amidino)dodecyl acrylamide (DAm), a reactive switchable surfactant, in an
      emulsion polymerization of styrene under CO(2) atmosphere. The resulted latex
      particles were readily coagulated by N(2) bubbling at 60  degrees C and
      redispersed by CO(2) bubbling and ultrasonication, which switched amidine
      moieties between neutral and ionic states. The coagulation/redispersion processes
      were repeatable. The prepared latexes showed good stabilities against
      electrolytes, especially with higher charges.

PMID- 22420826
TI  - The antioxidant paradox: less paradoxical now?
AB  - The term 'antioxidant paradox' is often used to refer to the observation that
      oxygen radicals and other reactive oxygen species are involved in several human
      diseases, but giving large doses of dietary antioxidant supplements to human
      subjects has, in most studies, demonstrated little or no preventative or
      therapeutic effect. Why should this be? First, the role of reactive oxygen
      species in the origin and/or progression of most human diseases is unclear,
      although they are probably important in cancer, neurodegenerative diseases and
      perhaps some others. Second, the endogenous antioxidant defences in the human
      body are complex, interlocking and carefully regulated. The body's 'total
      antioxidant capacity' seems unresponsive to high doses of dietary antioxidants,
      so that the amount of oxidative damage to key biomolecules is rarely changed.
      Indeed, manipulation of endogenous antioxidant levels (e.g. by supplying weak pro
      oxidants) may be a more useful approach to treatment and prevention of diseases
      in which reactive oxygen species are important than is consumption of large doses
      of dietary antioxidants.

PMID- 22420829
TI  - Linking agriculture and health in low- and middle-income countries: an
      interdisciplinary research agenda.
AB  - Recent global fluctuations in food prices and continuing environmental
      degradation highlight the future challenge of feeding a growing world population.
      However, current dialogues rarely address the relationship between agricultural
      changes and health. This relationship is traditionally associated with the role
      of food in nutrition and with food safety, and while these are key interactions,
      we show in this paper that the relationship is far more complex and interesting.
      Besides the direct effects of agriculture on population nutrition, agriculture
      also influences health through its impact on household incomes, economies and the
      environment. These effects are felt particularly in low- and middle-income
      countries, where dramatic changes are affecting the agriculture-health
      relationship, in particular the growth of nutrition-related chronic disease and
      the associated double burden of under- and over-nutrition. Greater understanding
      of the negative effects of agriculture on health is also needed. While
      lengthening food value chains make the chain of influence between agricultural
      policy, food consumption, nutrition and health more complex, there remain
      opportunities to improve health by changing agricultural systems. The first
      challenge in doing this, we suggest, is to improve our capacity to measure the
      impact of agricultural interventions on health outcomes, and vice versa.

PMID- 22420830
TI  - A randomised controlled trial comparing rocuronium priming, magnesium pre
      treatment and a combination of the two methods.
AB  - We investigated whether magnesium sulphate combined with rocuronium priming
      shortens the onset of neuromuscular blockade, compared with these methods used
      alone. Ninety-two patients scheduled for general anaesthesia were randomly
      allocated to one of four groups: controls were given 0.6 mg.kg(-1) rocuronium;
      patients in the prime group were given 0.06 mg.kg(-1) rocuronium three minutes
      before a further dose of 0.54 mg.kg(-1) rocuronium; patients in the magnesium
      group were given an infusion of 50 mg.kg(-1) magnesium sulphate before rocuronium
      and patients in the magnesium and prime group were given both the magnesium
      sulphate and the priming dose of rocuronium. Tracheal intubation was attempted 40
      s after the rocuronium injection. The time to onset of neuromuscular blockade was
      the primary outcome; duration of blockade and tracheal intubating conditions were
      also measured. The group allocation and study drugs were coded and concealed
      until statistical analyses were completed. The magnesium and prime group had the
      shortest mean (SD) onset time (55 (16)s; p < 0.001), and best tracheal intubating
      conditions (p < 0.05). No statistical difference was found for the duration of
      blockade. As for adverse events, a burning or heat sensation was reported in
      eight (35%) and six (26%) patients in the magnesium and magnesium and prime
      groups, respectively. The combination of magnesium sulphate and rocuronium
      priming accelerated the onset or neuromuscular blockade and improved rapid
      sequence intubating conditions, compared with either magnesium sulphate or
      priming used alone.

PMID- 22420832
TI  - 3D-modelling of radon-induced cellular radiobiological effects in bronchial
      airway bifurcations: direct versus bystander effects.
AB  - PURPOSE: The primary objective of this paper was to investigate the distribution
      of radiation doses and the related biological responses in cells of a central
      airway bifurcation of the human lung of a hypothetical worker of the New Mexico
      uranium mines during approximately 12 hours of exposure to short-lived radon
      progenies. MATERIALS AND METHODS: State-of-the-art computational modelling
      techniques were applied to simulate the relevant biophysical and biological
      processes in a central human airway bifurcation. RESULTS: The non-uniform
      deposition pattern of inhaled radon daughters caused a non-uniform distribution
      of energy deposition among cells, and of related cell inactivation and cell
      transformation probabilities. When damage propagation via bystander signalling
      was assessed, it produced more cell killing and cell transformation events than
      did direct effects. If bystander signalling was considered, variations of the
      average probabilities of cell killing and cell transformation were supra-linear
      over time. CONCLUSIONS: Our results are very sensitive to the radiobiological
      parameters, derived from in vitro experiments (e.g., range of bystander
      signalling), applied in this work and suggest that these parameters may not be
      directly applicable to realistic three-dimensional (3D) epithelium models.

PMID- 22420831
TI  - Following Ariadne's thread: a new perspective on RBR ubiquitin ligases.
AB  - Ubiquitin signaling pathways rely on E3 ligases for effecting the final transfer
      of ubiquitin from E2 ubiquitin conjugating enzymes to a protein target. Here we
      re-evaluate the hybrid RING/HECT mechanism used by the E3 family RING-between
      RINGs (RBRs) to transfer ubiquitin to substrates. We place RBRs into the context
      of current knowledge of HECT and RING E3s. Although not as abundant as the other
      types of E3s (there are only slightly more than a dozen RBR E3s in the human
      genome), RBRs are conserved in all eukaryotes and play important roles in
      biology. Re-evaluation of RBR ligases as RING/HECT E3s provokes new questions and
      challenges the field.

PMID- 22420833
TI  - Reinventing mesenchymal stromal cells.

PMID- 22420834
TI  - The role of virus-specific adoptive T-cell therapy in hematopoietic
      transplantation.
AB  - Viral infections are amongst the most significant complications following
      hematopoietic transplantation and occur principally because of a lack of virus
      specific T cells. Drug treatments are often suboptimal because of toxicity,
      limited viral sensitivity, or the potential for the development of resistance.
      Adoptive immunotherapy to restore virus-specific cellular immunity is clearly an
      attractive alternative and the pioneering work of the previous decade established
      that cellular products could be clinically effective. However, the techniques
      used in these early studies are expensive and relatively difficult to produce to
      GMP-compliant standards. This is major limitation to their wider application.
      This review concentrates on more recent studies detailing direct selection
      methodologies that are more suited to clinical scalability and more readily
      assessable in prospective randomised studies. We will also consider strategies
      that allow multiple pathogens to be targeted concurrently, and strategies that
      aim to extend the benefits of these technologies to transplant recipients whose
      donors are seronegative for these viruses and currently are most vulnerable to
      viral reactivations.

PMID- 22420835
TI  - Prediction of CD34(+) cell yield in hematopoietic cell products from children by
      peripheral blood CD34(+) cell counts.
AB  - BACKGROUND AIMS: Peripheral blood stem cells (PBSC) are increasingly used as an
      alternative to bone marrow in autologous transplantations. In adult patients, the
      peripheral blood CD34(+) cell count is a good predictor of CD34(+) cell yield in
      apheresis. However, the determinants of stem cell yield in the pediatric
      population have not been well established. METHODS: We retrospectively studied
      396 apheresis procedures in 301 pediatric patients. Receiver operating
      characteristic (ROC) curves based on pre-apheresis peripheral blood CD34(+) cell
      counts were generated to facilitate prediction of the optimal timing of PBSC
      collection. The associations between CD34(+) cell yield and age and mobilization
      regimen were analyzed. RESULTS: Significant differences in CD34(+) cell yield
      among different age groups were observed. Furthermore, higher CD34(+) cell yields
      were obtained in patients receiving chemotherapy as part of the mobilization
      regimen than those without chemotherapy. A correlation was noted between the
      CD34(+) cell yield and blood surrogate markers, including white blood cell count,
      absolute neutrophil count and pre-apheresis peripheral blood CD34(+) cell count.
      Cut-off values of > 35 CD34(+) cells/MUL in patients < 15 years old and > 45
      CD34(+) cells/MUL in patients >= 15 years old were strong predictors of an
      adequate PBSC collection in one apheresis session. For clinical use, ROC curves
      and tables were generated to assist advance planning for PBSC collection.
      CONCLUSIONS: The pre-apheresis peripheral blood CD34(+) cell count is most useful
      in predicting PBSC yield. Our new cut-off values have better operating
      characteristics for children than the conventional value of 20 CD34(+) cells/MUL
      used for adults.

PMID- 22420836
TI  - Frost resistance of reproductive tissues during various stages of development in
      high mountain plants.
AB  - Frost resistance of reproductive vs aboveground vegetative structures was
      determined for six common European high alpine plant species that can be exposed
      to frosts throughout their whole reproductive cycle. Freezing tests were carried
      out in the bud, anthesis and fruit stage. Stigma and style, ovary, placenta,
      ovule, flower stalk/peduncle and, in Ranunculus glacialis, the receptacle were
      separately investigated. In all species, the vegetative organs tolerated on an
      average 2-5 K lower freezing temperatures than the most frost-susceptible
      reproductive structures that differed in their frost resistance. In almost all
      species, stigma, style and the flower stalk/peduncle were the most frost
      susceptible reproductive structures. Initial frost damage (LT10) to the most
      susceptible reproductive structure usually occurred between -2 and -4 degrees C
      independent of the reproductive stage. The median LT50 across species for stigma
      and style ranged between -3.4 and -3.7 degrees C and matched the mean ice
      nucleation temperature (-3.7 +/- 1.4 degrees C). In R. glacialis, the flower
      stalk was the most frost-susceptible structure (-5.4 degrees C), and was in
      contrast to the other species ice-tolerant. The ovule and the placenta were
      usually the most frost-resistant structures. During reproductive development,
      frost resistance (LT50) of single reproductive structures mostly showed no
      significant change. However, significant increases or decreases were also
      observed (2.1 +/- 1.2 K). Reproductive tissues of nival species generally
      tolerated lower temperatures than species occurring in the alpine zone. The low
      frost resistance of reproductive structures before, during and shortly after
      anthesis increases the probability of frost damage and thus, may restrict
      successful sexual plant reproduction with increasing altitude.

PMID- 22420837
TI  - Clinical evaluation of gauze-based negative pressure wound therapy in challenging
      wounds.
AB  - The aim of this randomised clinical study was to evaluate the effectiveness and
      safety of gauze-based negative pressure wound therapy (NPWT) in patients with
      challenging wounds. A total of 50 consecutive patients who had wound drainage for
      more than 5 days, required open wound management and had existence of culture
      positive infection were included the study. In this study, gauze-based NPWT was
      compared with conventional dressing therapy in the treatment of patients with
      difficult-to-heal wounds. The patients were randomly divided into two groups.
      Group I (n = 25) was followed by conventional antiseptic (polyhexanide solution)
      dressings, and group II (n = 25) was treated with saline-soaked antibacterial
      gauze-based NPWT. The wounds' sizes, number of debridement, bacteriology and
      recurrence were compared between group I and group II. The mean age of the
      patients was 59.50 years (range 23-97). In group I, average wound sizes of pre-
      and post-treatment periods were 50.60 +/- 55.35 and 42.50 +/- 47.92 cm(2),
      respectively (P < 0.001). Average duration of treatment was 25.52 +/- 16.99 days,
      and average wound size reduction following the treatment was 19.99% in this
      group. In group II, the wounds displayed considerable shrinkage, accelerated
      granulation tissue formation, decreased and cleared away exudate. The average
      wound sizes in the pre- and post-treatment periods were 98.44 +/- 100.88 and
      72.08 +/- 75.78 cm(2) , respectively (P < 0.001). Average duration of treatment
      was 11.96 +/- 2.48 days, and average wound size reduction following the treatment
      was 32.34%. The patients treated with antibacterial gauze-based NPWT had a
      significantly reduced recurrence (2 wounds versus 14 wounds, P = 0.001), and
      increased number of the culture-negative cases (22 wounds versus 16 wounds, P <
      0.047) in a follow-up period of 12 months. There was a statistically significant
      difference between two groups in all measurements. As a result, we can say that
      the gauze-based NPWT is a safe and effective method in the treatment of
      challenging infective wounds when compared with conventional wound management.

PMID- 22420839
TI  - A model of the pre-assessment learning effects of assessment is operational in an
      undergraduate clinical context.
AB  - BACKGROUND: No validated model exists to explain the learning effects of
      assessment, a problem when designing and researching assessment for learning. We
      recently developed a model explaining the pre-assessment learning effects of
      summative assessment in a theory teaching context. The challenge now is to
      validate this model. The purpose of this study was to explore whether the model
      was operational in a clinical context as a first step in this process. METHODS:
      Given the complexity of the model, we adopted a qualitative approach. Data from
      in-depth interviews with eighteen medical students were subject to content
      analysis. We utilised a code book developed previously using grounded theory.
      During analysis, we remained alert to data that might not conform to the coding
      framework and open to the possibility of deploying inductive coding. Ethical
      clearance and informed consent were obtained. RESULTS: The three components of
      the model i.e., assessment factors, mechanism factors and learning effects were
      all evident in the clinical context. Associations between these components could
      all be explained by the model. Interaction with preceptors was identified as a
      new subcomponent of assessment factors. The model could explain the
      interrelationships of the three facets of this subcomponent i.e., regular
      accountability, personal consequences and emotional valence of the learning
      environment, with previously described components of the model. CONCLUSIONS: The
      model could be utilized to analyse and explain observations in an assessment
      context different to that from which it was derived. In the clinical setting, the
      (negative) influence of preceptors on student learning was particularly
      prominent. In this setting, learning effects resulted not only from the high
      stakes nature of summative assessment but also from personal stakes, e.g. for
      esteem and agency. The results suggest that to influence student learning,
      consequences should accrue from assessment that are immediate, concrete and
      substantial. The model could have utility as a planning or diagnostic tool in
      practice and research settings.

PMID- 22420838
TI  - Assessment of the safety and feasibility of administering anti-pyretic therapy in
      critically ill adults: study protocol of a randomized trial.
AB  - BACKGROUND: Fever is one of the most commonly observed abnormal signs in patients
      with critical illness. However, there is a paucity of evidence to guide the
      management of febrile patients without acute brain injury and little is known
      about the biologic response to treatment of fever. As such, observational studies
      suggest that the treatment of fever is inconsistent. This pilot clinical trial
      will assess the safety and feasibility of treating febrile critically ill adult
      patients with an aggressive versus a permissive temperature control strategy. The
      biologic response to these two different temperature control strategies will also
      be assessed through analysis of a panel of inflammatory mediators. FINDINGS: The
      study population will include febrile adult patients admitted to one of two
      general medical-surgical intensive care units (ICUs) in Calgary, Alberta, Canada.
      Patients will be randomized to either an aggressive or permissive fever treatment
      strategy. The aggressive group will receive acetaminophen 650 mg enterally every
      6 hours upon reaching a temperature >= 38.3  degrees C and external cooling will
      be initiated for temperatures >= 39.5  degrees C, whereas the permissive group
      will receive acetaminophen 650 mg every 6 hours upon reaching a temperature >=
      40.0  degrees C and external cooling for temperatures >= 40.5  degrees C. The
      study will take place over 12 months with the goal of enrolling 120 patients. The
      primary outcome will be 28-day mortality after study enrolment, with secondary
      outcomes that will include markers of feasibility (e.g. the enrolment rate, and
      the number of protocol violations), and levels of select inflammatory and anti
      inflammatory mediators. DISCUSSION: Results from this study will lead to a better
      understanding of the inflammatory effects of anti-pyretic therapy and will
      evaluate the feasibility of a future clinical trial to establish the best
      treatment of fever observed in nearly one half of patients admitted to adult
      ICUs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01173367.

PMID- 22420840
TI  - Reformulation in the phase plane enhances smoothness rater accuracy in stroke.
AB  - To improve the characterization of motor impairment, we compared the
      sensitivities of a phase plane metric with temporal domain measures derived from
      integrated squared jerk (ISJ). Five subjects with stroke and a cohort of 21
      neurologically intact volunteers performed self-paced, isolated elbow flexions.
      Analysis of angular trajectories from the stroke group revealed that temporal
      domain metrics failed to detect a performance deficit at the p < .05 level, while
      the phase plane metric did resolve a deficit (p < .01). When applied to a subset
      of movements with arrest periods, the phase measure also uniquely identified
      impairment (Wilcoxon rank-sum test, p < .001). Finally, when tested on a data
      driven model, the phase measure, but not temporal metrics, increased
      monotonically with the severity of trajectory distortions. We conclude that
      motion smoothness can be accurately measured in the phase plane.

PMID- 22420841
TI  - A comparison of azithromycin and tobramycin eye drops on epithelial wound healing
      and tolerance after penetrating keratoplasty.
AB  - PURPOSE: After keratoplasty, antibiotic eye drops are used to prevent ocular
      infection until the recipient corneal epithelium has healed. We compared the
      effects of azithromycin, a new macrolide, with the effect of the standard
      antibiotics, tobramycin, on the (i) prevention of infection, (ii) epithelial
      healing, and (iii) ocular tolerance after penetrating keratoplasty. METHODS: In
      this prospective, single-center, randomized study, patients undergoing
      penetrating keratoplasty received postoperative topical dexamethasone and either
      azithromycin (n=23; Azyter((r)); one drop twice daily for 3 days) or tobramycin
      (n=23; Tobrex((r)); 1 drop 4 times daily until complete re-epithelialization).
      Daily slit-lamp examination with fluorescein was performed, and photographs were
      taken to digitally assess the re-epithelialized surface area. Daily
      questionnaires assessed ocular comfort and pain. RESULTS: There were no cases of
      infection in either group. The re-epithelialized area of the corneal graft
      increased at a similar rate in each group, with no difference between the groups
      on any day. The mean+/-SD days until complete re-epithelialization did not differ
      between tobramycin (4.14+/-1.17) and azithromycin (4.13+/-1.82) (P=0.89).
      Superficial punctate keratitis scores were similar for tobramycin (1.39) and
      azithromycin (1.34). Pain and discomfort scores improved each day after surgery
      with no differences between the groups on any day. CONCLUSION: Postkeratoplasty
      epithelial healing and ocular tolerance were not significantly different between
      the azithromycin- and tobramycin-treatment groups. Our results support the use of
      azithromycin as an alternative to tobramycin after corneal surgery such as
      keratoplasty.

PMID- 22420843
TI  - Randomized controlled trial of sirolimus for renal transplant recipients at high
      risk for nonmelanoma skin cancer.
AB  - Sirolimus has antineoplastic effects and may reduce skin cancer rates in kidney
      transplant patients. This prospective, multicenter, randomized, open-label,
      controlled trial randomized 86 kidney transplant recipients (>=1 year
      posttransplant) with history of nonmelanoma skin cancer (NMSC) to continue
      calcineurin inhibitor (CNI) or convert to sirolimus. Patients were stratified by
      number of NMSC lesions (0-5, 6-20) in previous year. Primary end point was number
      of biopsy-confirmed new NMSC lesions per patient-year. Yearly NMSC rate was
      significantly lower with sirolimus (1.31 vs. 2.48 lesions/patient-year; p =
      0.022). Squamous cell carcinoma occurred at a lower rate in the sirolimus versus
      CNI group (p = 0.038); basal cell carcinoma rate was similar in both. A lower
      proportion of patients receiving sirolimus developed new or recurrent NMSC (56.4%
      vs. 80.9%; p = 0.015) or new squamous cell carcinoma (41.0% vs. 70.2%; p =
      0.006). No sirolimus patients and one CNI continuation patient experienced acute
      rejection. Incidence of treatment-emergent adverse events was similar between
      groups; however, discontinuation rates related to adverse events were
      significantly higher with sirolimus (46.2% vs. 0%; p < 0.001). In kidney
      transplant recipients with history of NMSC, conversion from CNI to sirolimus
      reduced rates of NMSC, without increasing acute rejection risk.

PMID- 22420842
TI  - The use of drinking and condom-related protective strategies in association with
      condom use and sex-related alcohol use.
AB  - Approximately 40% of American college students engage in heavy drinking, and
      heavy drinking is associated with sexual risk behaviors. It is imperative to gain
      a better understanding of the relationship between alcohol and sexual risk
      behaviors for prevention efforts. This article examined the use of drinking and
      condom-related protective behavioral strategies (PBS) in relation to drinking and
      condom-use outcomes in 436 college students. Drinking PBS are related to drinking
      and negative alcohol-related consequences. Furthermore, condom-related PBS are
      related to condom use; however, it is unclear if drinking PBS are related to
      condom use, particularly condom use when drinking. It was hypothesized that the
      use of drinking PBS would be related to less alcohol-related sexual activity,
      that the use of condom-related PBS would be related to greater condom use and
      condom use while drinking, and that drinking PBS would be related to greater
      condom use, especially condom use when drinking. It was found that condom-related
      PBS were associated with condom behavior and drinking PBS were related to
      drinking behavior, but we did not find support for a relationship between
      drinking PBS and condom use. This suggests that condom-related PBS may be a more
      effective target for increasing condom use than drinking PBS alone.

PMID- 22420845
TI  - A 60-year-old woman with subcutaneous nodules on the thigh.

PMID- 22420844
TI  - First-in-class, dual-action, 3,5-disubstituted indole derivatives having human
      nitric oxide synthase (nNOS) and norepinephrine reuptake inhibitory (NERI)
      activity for the treatment of neuropathic pain.
AB  - A family of different 3,5-disubstituted indole derivatives having 6-membered
      rings were designed, synthesized, and demonstrated inhibition of human nitric
      oxide synthase (NOS) with norepinephrine reuptake inhibitory activity (NERI). The
      structure-activity relationship (SAR) within the cyclohexane ring showed the cis
      isomers to be more potent for neuronal NOS and selective over endothelial NOS
      compared to their trans-counterparts. Compounds, such as cis-(+)-37, exhibited
      dual nNOS and NET inhibition (IC(50) of 0.56 and 1.0 MUM, respectively) and
      excellent selectivity (88-fold and 12-fold) over eNOS and iNOS, respectively. The
      lead compound (cis-(+)-37) showed lack of any direct vasoconstriction or
      inhibition of ACh-mediated vasorelaxation in isolated human coronary arteries.
      Additionally, cis-(+)-37 was effective at reversing both allodynia and thermal
      hyperalgesia in a standard Chung (spinal nerve ligation) rat neuropathic pain
      model. Overall, the data suggest that cis-(+)-37 is a promising dual action
      development candidate having therapeutic potential for the treatment of
      neuropathic pain.

PMID- 22420846
TI  - Correction to Preparation and characterization of poly(phthalazinone ether
      sulfone) hollow fiber ultrafiltration membranes.

PMID- 22420848
TI  - Molecular dynamics simulation of nitric oxide in myoglobin.
AB  - The infrared (IR) spectroscopy and ligand migration of photodissociated nitric
      oxide (NO) in and around the active sites in myoglobin (Mb) are investigated. A
      distributed multipolar model for open-shell systems is developed and used, which
      allows one to realistically describe the charge distribution around the diatomic
      probe molecule. The IR spectra were computed from the trajectories for two
      conformational substates at various temperatures. The lines are narrow (width of
      3-7 cm(-1) at 20-100 K), in agreement with the experimental observations where
      they have widths of 4-5 cm(-1) at 4 K. It is found that within one conformational
      substate (B or C) the splitting of the spectrum can be correctly described
      compared with recent experiments. Similar to photodissociated CO in Mb,
      additional substates exist for NO in Mb, which are separated by barriers below 1
      kcal/mol. Contrary to full quantum mechanical calculations, however, the force
      field and mixed QM/MM simulations do not correctly describe the relative shifts
      between the B- and C-states relative to gas-phase NO. Free energy simulations
      establish that NO preferably localizes in the distal site and the barrier for
      migration to the neighboring Xe4 pocket is DeltaG(B->C)(?) = 1.7-2.0 kcal/mol.
      The reverse barrier is DeltaG(B<-C)(?) = 0.7 kcal/mol, which agrees well with the
      experimental value of 0.7 kcal/mol, estimated from kinetic data.

PMID- 22420849
TI  - Bacteriophage electron microscopy.
AB  - Since the advent of the electron microscope approximately 70 years ago, bacterial
      viruses and electron microscopy are inextricably linked. Electron microscopy
      proved that bacteriophages are particulate and viral in nature, are complex in
      size and shape, and have intracellular development cycles and assembly pathways.
      The principal contribution of electron microscopy to bacteriophage research is
      the technique of negative staining. Over 5500 bacterial viruses have so far been
      characterized by electron microscopy, making bacteriophages, at least on paper,
      the largest viral group in existence. Other notable contributions are
      cryoelectron microcopy and three-dimensional image reconstruction, particle
      counting, and immunoelectron microscopy. Scanning electron microscopy has had
      relatively little impact. Transmission electron microscopy has provided the basis
      for the recognition and establishment of bacteriophage families and is one of the
      essential criteria to classify novel viruses into families. It allows for instant
      diagnosis and is thus the fastest diagnostic technique in virology. The most
      recent major contribution of electron microscopy is the demonstration that the
      capsid of tailed phages is monophyletic in origin and that structural links exist
      between some bacteriophages and viruses of vertebrates and archaea. DNA
      sequencing cannot replace electron microscopy and vice versa.

PMID- 22420850
TI  - Postcards from the edge: structural genomics of archaeal viruses.
AB  - Ever since their discovery, archaeal viruses have fascinated biologists with
      their unusual virion morphotypes and their ability to thrive in extreme
      environments. Attempts to understand the biology of these viruses through genome
      sequence analysis were not efficient. Genomes of archaeoviruses proved to be
      terra incognita with only a few genes with predictable functions but uncertain
      provenance. In order to facilitate functional characterization of archaeal virus
      proteins, several research groups undertook a structural genomics approach. This
      chapter summarizes the outcome of these efforts. High-resolution structures of 30
      proteins encoded by archaeal viruses have been solved so far. Some of these
      proteins possess new structural folds, whereas others display previously known
      topologies, albeit without detectable sequence similarity to their structural
      homologues. Structures of the major capsid proteins have illuminated intriguing
      evolutionary connections between viruses infecting hosts from different domains
      of life and also revealed new structural folds not yet observed in currently
      known bacterial and eukaryotic viruses. Structural studies, discussed here, have
      advanced our understanding of the archaeal virosphere and provided precious
      information on different aspects of biology of archaeal viruses and evolution of
      viruses in general.

PMID- 22420851
TI  - Sputnik, a virophage infecting the viral domain of life.
AB  - This chapter discusses the astonishing discovery of the Sputnik virophage, a new
      virus infecting giant viruses of the genera Mimivirus and Mamavirus. While other
      virophages have also since been described, this chapter focuses mainly on
      Sputnik, which is the best described. We detail the general properties of the
      virophage life cycle, as well as its hosts, genomic characteristics, ecology, and
      origin. In addition to genetic, phylogenetic, and structural evidence, the
      existence of virophages has deeply altered our view of the tripartite division of
      life to include the addition of a fourth domain constituted of the
      nucleocytoplasmic large DNA viruses, an important point that is discussed.

PMID- 22420852
TI  - Bacteriophage-encoded bacterial virulence factors and phage-pathogenicity island
      interactions.
AB  - The role of bacteriophages as natural vectors for some of the most potent
      bacterial toxins is well recognized and includes classical type I membrane-acting
      superantigens, type II pore-forming lysins, and type III exotoxins, such as
      diphtheria and botulinum toxins. Among Gram-negative pathogens, a novel class of
      bacterial virulence factors called effector proteins (EPs) are phage encoded
      among pathovars of Escherichia coli, Shigella spp., and Salmonella enterica. This
      chapter gives an overview of the different types of virulence factors encoded
      within phage genomes based on their role in bacterial pathogenesis. It also
      discusses phage-pathogenicity island interactions uncovered from studies of phage
      encoded EPs. A detailed examination of the filamentous phage CTXphi that encodes
      cholera toxin is given as the sole example to date of a single-stranded DNA phage
      that encodes a bacterial toxin.

PMID- 22420854
TI  - Phage lambda--new insights into regulatory circuits.
AB  - Bacteriophage lambda, rediscovered in the early 1950s, has served as a model in
      molecular biology studies for decades. Although currently more complex organisms
      and more complicated biological systems can be studied, this phage is still an
      excellent model to investigate principles of biological processes occurring at
      the molecular level. In fact, very few other biological models provide
      possibilities to examine regulations of biological mechanisms as detailed as
      performed with lambda. In this chapter, recent advances in our understanding of
      mechanisms of bacteriophage lambda development are summarized and discussed.
      Particularly, studies on (i) phage DNA injection, (ii) molecular bases of the
      lysis-versus-lysogenization decision and the lysogenization process itself, (iii)
      prophage maintenance and induction, (iv), lambda DNA replication, (v) phage
      encoded recombination systems, (vi) transcription antitermination, (vii)
      formation of the virion structure, and (viii) lysis of the host cell, as
      published during several past years, will be presented.

PMID- 22420853
TI  - Structure, assembly, and DNA packaging of the bacteriophage T4 head.
AB  - The bacteriophage T4 head is an elongated icosahedron packed with 172 kb of
      linear double-stranded DNA and numerous proteins. The capsid is built from three
      essential proteins: gp23*, which forms the hexagonal capsid lattice; gp24*, which
      forms pentamers at 11 of the 12 vertices; and gp20, which forms the unique
      dodecameric portal vertex through which DNA enters during packaging and exits
      during infection. Intensive work over more than half a century has led to a deep
      understanding of the phage T4 head. The atomic structure of gp24 has been
      determined. A structural model built for gp23 using its similarity to gp24 showed
      that the phage T4 major capsid protein has the same fold as numerous other
      icosahedral bacteriophages. However, phage T4 displays an unusual membrane and
      portal initiated assembly of a shape determining self-sufficient scaffolding
      core. Folding of gp23 requires the assistance of two chaperones, the Escherichia
      coli chaperone GroEL acting with the phage-coded gp23-specific cochaperone, gp31.
      The capsid also contains two nonessential outer capsid proteins, Hoc and Soc,
      which decorate the capsid surface. Through binding to adjacent gp23 subunits, Soc
      reinforces the capsid structure. Hoc and Soc have been used extensively in
      bipartite peptide display libraries and to display pathogen antigens, including
      those from human immunodeficiency virus (HIV), Neisseria meningitides, Bacillus
      anthracis, and foot and mouth disease virus. The structure of Ip1*, one of a
      number of multiple (>100) copy proteins packed and injected with DNA from the
      full head, shows it to be an inhibitor of one specific restriction endonuclease
      specifically targeting glycosylated hydroxymethyl cytosine DNA. Extensive
      mutagenesis, combined with atomic structures of the DNA packaging/terminase
      proteins gp16 and gp17, elucidated the ATPase and nuclease functional motifs
      involved in DNA translocation and headful DNA cutting. The cryoelectron
      microscopy structure of the T4 packaging machine showed a pentameric motor
      assembled with gp17 subunits on the portal vertex. Single molecule optical
      tweezers and fluorescence studies showed that the T4 motor packages DNA at the
      highest rate known and can package multiple segments. Forster resonance energy
      transfer-fluorescence correlation spectroscopy studies indicate that DNA gets
      compressed in the stalled motor and that the terminase-to-portal distance changes
      during translocation. Current evidence suggests a linear two-component (large
      terminase plus portal) translocation motor in which electrostatic forces
      generated by ATP hydrolysis drive DNA translocation by alternating the motor
      between tensed and relaxed states.

PMID- 22420855
TI  - The secret lives of mycobacteriophages.
AB  - The study of mycobacteriophages provides insights into viral diversity and
      evolution, as well as the genetics and physiology of their pathogenic hosts.
      Genomic characterization of 80 mycobacteriophages reveals a high degree of
      genetic diversity and an especially rich reservoir of interesting genes. These
      include a vast number of genes of unknown function that do not match known
      database entries and many genes whose functions can be predicted but which are
      not typically found as components of phage genomes. Thus many mysteries surround
      these genomes, such as why the genes are there, what do they do, how are they
      expressed and regulated, how do they influence the physiology of the host
      bacterium, and what forces of evolution directed them to their genomic homes?
      Although the genetic diversity and novelty of these phages is full of intrigue,
      it is a godsend for the mycobacterial geneticist, presenting an abundantly rich
      toolbox that can be exploited to devise new and effective ways for understanding
      the genetics and physiology of human tuberculosis. As the number of sequenced
      genomes continues to grow, their mysteries continue to thicken, and the time has
      come to learn more about the secret lives of mycobacteriophages.

PMID- 22420856
TI  - Role of CRISPR/cas system in the development of bacteriophage resistance.
AB  - Acquisition of foreign DNA can be of advantage or disadvantage to the host cell.
      New DNAs can increase the fitness of an organism to certain environmental
      conditions; however, replication and maintenance of incorporated nucleotide
      sequences can be a burden for the host cell. These circumstances have resulted in
      the development of certain cellular mechanisms limiting horizontal gene transfer,
      including the immune system of vertebrates or RNA interference mechanisms in
      eukaryotes. Also, in prokaryotes, specific systems have been characterized, which
      are aimed especially at limiting the invasion of bacteriophage DNA, for example,
      adsorption inhibition, injection blocking, restriction/modification, or abortive
      infection. Quite recently, another distinct mechanism limiting horizontal
      transfer of genetic elements has been identified in procaryotes and shown to
      protect microbial cells against exogenous nucleic acids of phage or plasmid
      origin. This system has been termed CRISPR/cas and consists of two main
      components: (i) the CRISPR (clustered, regularly interspaced short palindromic
      regions) locus and (ii) cas genes, encoding CRISPR-associated (Cas) proteins. In
      simplest words, the mechanism of CRISPR/cas activity is based on the active
      integration of small fragments (proto-spacers) of the invading DNAs (phage or
      plasmids) into microbial genomes, which are subsequently transcribed into short
      RNAs that direct the degradation of foreign invading DNA elements. In this way,
      the host organism acquires immunity toward mobile elements carrying matching
      sequences. The CRISPR/cas system is regarded as one of the earliest defense
      system that has evolved in prokaryotic organisms. It is inheritable, but at the
      same time is unstable when regarding the evolutionary scale. Comparative sequence
      analyses indicate that CRISPR/cas systems play an important role in the evolution
      of microbial genomes and their predators, bacteriophages.

PMID- 22420857
TI  - Pseudolysogeny.
AB  - Pseudolysogeny can be defined as the stage of stalled development of a
      bacteriophage in a host cell without either multiplication of the phage genome
      (as in lytic development) or its replication synchronized with the cell cycle and
      stable maintenance in the cell line (as in lysogenization), which proceeds with
      no viral genome degradation, thus allowing the subsequent restart of virus
      development. This phenomenon is usually caused by unfavorable growth conditions
      for the host cell (such as starvation) and is terminated with initiation of
      either true lysogenization or lytic growth when growth conditions improve.
      Pseudolysogeny has been known for tens of years; however, its role has often been
      underestimated. Currently, it is being considered more often as an important
      aspect of phage-host interactions. The reason for this is mostly an increased
      interest in phage-host interactions in the natural environment. Pseudolysogeny
      seems to play an important role in phage survival, as bacteria in a natural
      environment are starved or their growth is very slow. This phenomenon can be an
      important aspect of phage-dependent bacterial mortality and may influence the
      virulence of some bacterial strains.

PMID- 22420858
TI  - Role of host factors in bacteriophage phi29 DNA replication.
AB  - During the course of evolution, viruses have learned to take advantage of the
      natural resources of their hosts for their own benefit. Due to their small
      dimension and limited size of genomes, bacteriophages have optimized the
      exploitation of bacterial host factors to increase the efficiency of DNA
      replication and hence to produce vast progeny. The Bacillus subtilis phage phi29
      genome consists of a linear double-stranded DNA molecule that is duplicated by
      means of a protein-primed mode of DNA replication. Its genome has been shown to
      be topologically constrained at the size of the bacterial nucleoid and, as to
      avoid generation of positive supercoiling ahead of the replication forks, the
      bacterial DNA gyrase is used by the phage. In addition, the B. subtilis actin
      like MreB cytoskeleton plays a crucial role in the organization of phi29 DNA
      replication machinery in peripheral helix-like structures. Thus, in the absence
      of an intact MreB cytoskeleton, phi29 DNA replication is severely impaired.
      Importantly, MreB interacts directly with the phage membrane protein p16.7,
      responsible for attaching phi29 DNA at the cell membrane. Moreover, the phi29
      encoded protein p56 inhibits host uracil-DNA glycosylase activity and has been
      proposed to be a defense mechanism developed by the phage to prevent the action
      of the base excision repair pathway if uracil residues arise in replicative
      intermediates. All of them constitute incoming examples on how viruses have
      profited from the cellular machinery of their hosts.

PMID- 22420859
TI  - Advances in Virus Research. Bacteriophages, part A. Preface.

PMID- 22420860
TI  - Individualized guidelines for the management of aggression in dementia - Part 2:
      appraisal of current guidelines.
AB  - BACKGROUND: Individualized guidelines have the potential to offer clinicians
      assistance in decision-making at the point of consultation to improve health
      outcomes for patients. This project aims to develop individualized guidelines for
      the management of aggression in dementia. At an earlier stage, we developed a map
      of concepts to consider when managing aggression. The purpose of the current
      study is to appraise paper-based guidelines for their representation of these
      concepts. METHODS: Two reviewers used a four-point scale (absent, weak, moderate,
      strong) to rate the guidelines on their representation of concepts relating to
      the patient, the aggression and dementia disorder, the treatment, and the
      guidelines themselves. Consensus was reached on inconsistent scores. RESULTS:
      Sixteen guidelines published since 2005 were evaluated for their representation
      of 13 key concepts. Pharmacological and non-pharmacological interventions were
      strongly represented overall in the guidelines, in conjunction with a
      consideration of the individual characteristics of the patients and their
      environment. Recommendations based on the presentation of the aggressive
      symptoms, goals of treatment, and theory of the cause of the aggression were
      moderately represented in the guidelines. Recommendations for the principles of
      restraint use and emergency treatment, as well as a consideration of the personal
      history of the patient, were poorly represented. Only 6 of 16 guidelines gave
      details of the expected review. CONCLUSION: Concepts important to the management
      of aggression in dementia are missing in the majority of published guidelines on
      dementia. This limits the ability of these tools to guide clinical practice
      effectively.

PMID- 22420861
TI  - Revealing the mechanisms behind SnO2 nanoparticle formation and growth during
      hydrothermal synthesis: an in situ total scattering study.
AB  - The formation and growth mechanisms in the hydrothermal synthesis of SnO(2)
      nanoparticles from aqueous solutions of SnCl(4).5H(2)O have been elucidated by
      means of in situ X-ray total scattering (PDF) measurements. The analysis of the
      data reveals that when the tin(IV) chloride precursor is dissolved, chloride ions
      and water coordinate octahedrally to tin(IV), forming aquachlorotin(IV) complexes
      of the form [SnCl(x)(H(2)O)(6-x)]((4-x)+) as well as hexaaquatin(IV) complexes
      [Sn(H(2)O)(6-y)(OH)(y)]((4-y)+). Upon heating, ellipsoidal SnO(2) nanoparticles
      are formed uniquely from hexaaquatin(IV). The nanoparticle size and morphology
      (aspect ratio) are dependent on both the reaction temperature and the precursor
      concentration, and particles as small as ~2 nm can be synthesized. Analysis of
      the growth curves shows that Ostwald ripening only takes place above 200  degrees
      C, and in general the growth is limited by diffusion of precursor species to the
      growing particle. The c-parameter in the tetragonal lattice is observed to expand
      up to 0.5% for particle sizes down to 2-3 nm as compared to the bulk value.
      SnO(2) nanoparticles below 3-4 nm do not form in the bulk rutile structure, but
      as an orthorhombic structural modification, which previously has only been
      reported at pressures above 5 GPa. Thus, adjustment of the synthesis temperature
      and precursor concentration not only allows control over nanoparticle size and
      morphology but also the structure.

PMID- 22420862
TI  - The transcriptional response of mammalian cancer cells to irradiation is
      dominated by a cell cycle signature which is strongly attenuated in non-cancer
      cells and tissues.
AB  - PURPOSE: Our goal was to identify genes showing a general transcriptional
      response to irradiation in mammalian cells and to analyze their response in
      function of dose, time and quality of irradiation and of cell type. MATERIALS AND
      METHODS: We used a modified MIAME (Minimal Information About Microarray
      Experiments) protocol to import microarray data from 177 different irradiation
      conditions in the Radiation Genes database and performed cut-off-based selections
      and hierarchical gene clustering. RESULTS: We identified a set of 29 genes which
      respond to a wide range of irradiation conditions in different cell types and
      tissues. Functional analysis of the negatively modulated genes revealed a
      dominant signature of mitotic cell cycle regulation which appears both dose and
      time-dependent. This signature is prominent in cancer cells and highly
      proliferating tissues but it is strongly attenuated in non cancer cells.
      CONCLUSIONS: The transcriptional response of mammalian cancer cells to
      irradiation is dominated by a mitotic cell cycle signature both dose and time
      dependent. This core response, which is present in cancer cells and highly
      proliferating tissues such as skin, blood and lymph node, is weaker or absent in
      non-cancer cells and in liver and spleen. CDKN1A (cyclin-dependent kinase
      inhibitor 1A) appears as the most generally induced mammalian gene and its
      response (mostly dose- and time-independent) seems to go beyond the typical DNA
      damage response.

PMID- 22420863
TI  - Improved initial burst of estradiol organogel as long-term in situ drug delivery
      implant: formulation, in vitro and in vivo characterization.
AB  - OBJECTIVE: The present investigation was aimed at optimizing of estradiol (E2)
      loaded l-amino acid derivatives organogel formulations resulting in improved the
      high initial release problems and sustained release of E2. METHODS: The visco
      elastic properties of blank organogels were measured by rheometer. The E2
      organogel formulations were optimized using a central composite design. Also, the
      effect of gelator structure and composition of the gel formulations on release
      behavior (in vitro and in vivo) had been studied. RESULTS: The change of the
      gelator structure could affect significantly the stiffness of the implants. The
      release behavior of gel without N-Methyl-2-pyrrolidinone (NMP) was controlled by
      gel corrosion only. While the drug release of the gel with NMP was controlled by
      both corrosion and diffusion. The high initial release problems of the organogels
      were improved by optimizing the formulations. The system consisting by N-Lauroyl
      L-lysine methyl ester (LLM) derivative in the oil indicated the lowest initial
      drug release, showed a much lower blood drug level and maintained a steady state
      for nearly 1 month. CONCLUSION: Organogels based on L-lysine methyl ester
      derivative were ideal carriers for long-term parenteral administration of E2.

PMID- 22420864
TI  - Signaling-mediated control of ubiquitin ligases in endocytosis.
AB  - Ubiquitin-dependent regulation of endocytosis plays an important part in the
      control of signal transduction, and a critical issue in the understanding of
      signal transduction therefore relates to regulation of ubiquitination in the
      endocytic pathway. We discuss here what is known of the mechanisms by which
      signaling controls the activity of the ubiquitin ligases that specifically
      recognize the targets of ubiquitination on the endocytic pathway, and suggest
      alternative mechanisms that deserve experimental investigation.

PMID- 22420865
TI  - Choriocarcinoma of the lung masquerading as a persisting pregnancy of unknown
      location (PUL).

PMID- 22420866
TI  - Oxytocin prolongs the gastric emptying time in patients with diabetes mellitus
      and gastroparesis, but does not affect satiety or volume intake in patients with
      functional dyspepsia.
AB  - BACKGROUND: Oxytocin is released in response to a fatty meal. Blockage of the
      oxytocin receptor led to slower gastric emptying whereas stimulation resulted in
      less satiety in healthy volunteers. Patients with diabetes mellitus and
      gastroparesis lack oxytocin elevation, and dyspepsia is partly caused by reduced
      fundus accommodation causing early satiety and related symptoms. The aim of this
      study was thus to examine the effect of oxytocin on gastric emptying, satiety and
      volume intake in patients with gastrointestinal pathology. RESULTS: Gastric
      emptying scintigraphy was performed twice in 12 patients with diabetic
      gastroparesis, once with oxytocin and once with saline as intravenous infusions.
      The patients scored their sensation of satiety using a visual analogue scale
      (VAS). The gastric emptying in patients with gastroparesis was prolonged during
      oxytocin infusion (p = 0.034) without affecting satiety. A slow satiety drinking
      test was performed in 14 patients with functional dyspepsia. The patients scored
      their satiety every five minutes until maximal satiety was reached, and the total
      volume was determined. The VAS was also completed 30 minutes afterwards. The test
      was performed twice, once with oxytocin and once with saline as intravenous
      infusions. There was no difference in satiety scores or volume of nutrient intake
      between saline and oxytocin infusions, either before, during or after the meal.
      CONCLUSIONS: Oxytocin prolongs gastric emptying in patients with diabetes
      mellitus and gastroparesis, but has no effect on volume of nutrient intake or
      satiety and other related symptoms in patients with functional dyspepsia.

PMID- 22420867
TI  - Weak D caused by a founder deletion in the RHD gene.
AB  - BACKGROUND: The RhD blood group system exemplifies a genotype-phenotype
      correlation by virtue of its highly polymorphic and immunogenic nature. Weak D
      phenotypes are generally thought to result from missense mutations leading to
      quantitative change of the D antigen in the red blood cell membrane or
      intracellularly. STUDY DESIGN AND METHODS: Different sets of polymerase chain
      reaction primers were designed to map and clone a deletion involving RHD Exon 10,
      which was found in approximately 3% of approximately 2000 RHD hemizygous subjects
      with D phenotype ambiguity. D antigen density was measured by flow cytometry.
      Transcript analysis was carried out by 3'-rapid amplification of complementary
      DNA ends. Haplotype analysis was performed by microsatellite genotyping. RESULTS:
      A 5405-bp deletion that removed nearly two-thirds of Intron 9 and almost all of
      Exon 10 of the RHD gene was characterized. It is predicted to result in the
      replacement of the last eight amino acids of the wild-type RhD protein by another
      four amino acids. The mean RhD antigen density from two deletion carriers was
      determined to be only 30. A consensus haplotype could be deduced from the
      deletion carriers based on the microsatellite genotyping data. CONCLUSION: The
      currently reported deletion was derived from a common founder. This deletion
      appears to represent not only the first large deletion associated with weak D but
      also the weakest of weak D alleles so far reported. This highly unusual genotype
      phenotype relationship may be attributable to the additive effect of three
      distinct mechanisms that affect mRNA formation, mRNA stability, and RhD/ankyrin-R
      interaction, respectively.

PMID- 22420868
TI  - Is there scope for community health nurses to address lifestyle risk factors? the
      community nursing SNAP trial.
AB  - BACKGROUND: This paper examines the opportunity and need for lifestyle
      interventions for patients attending generalist community nursing services in
      Australia. This will help determine the scope for risk factor management within
      community health care by generalist community nurses (GCNs). METHODS: This was a
      quasi-experimental study conducted in four generalist community nursing services
      in NSW, Australia. Prior to service contacts, clients were offered a computer
      assisted telephone interview to collect baseline data on socio-demographics,
      health conditions, smoking status, physical activity levels, alcohol consumption,
      height and weight, fruit and vegetable intake and 'readiness-to-change' for
      lifestyle risk factors. RESULTS: 804 clients participated (a response rate of
      34.1%). Participants had higher rates of obesity (40.5% vs 32.1%) and higher
      prevalence of multiple risk factors (40.4% vs 29.5%) than in the general
      population. Few with a SNAPW (Smoking-Nutrition-Alcohol-Physical-Activity-Weight)
      risk factor had received advice or referral in the previous 3 months. The
      proportion of clients identified as at risk and who were open to change (i.e.
      contemplative, in preparation or in action phase) were 65.0% for
      obese/overweight; 73.8% for smokers; 48.2% for individuals with high alcohol
      intake; 83.5% for the physically inactive and 59.0% for those with poor
      nutrition. CONCLUSIONS: There was high prevalence of lifestyle risk factors.
      Although most were ready to change, few clients recalled having received any
      recent lifestyle advice. This suggests that there is considerable scope for
      intervention by GCNs. The results of this trial will shed light on how best to
      implement the lifestyle risk factor management in routine practice.

PMID- 22420869
TI  - Patient-reported outcomes in trials of incretin-based therapies in patients with
      type 2 diabetes mellitus.
AB  - Incretin-based therapies have a glucose-dependent mode of action that results in
      excellent glucose-lowering efficacy with very low risk of hypoglycaemia, and
      weight neutrality [dipeptidyl peptidase-4 (DPP-4) inhibitors] or weight loss
      [glucagon-like peptide-1 (GLP-1) receptor agonists], in people with type 2
      diabetes mellitus (T2DM). Patient-reported outcomes (PROs) complement physician
      evaluations of efficacy and tolerability and offer insights into the subjective
      experience of using modern diabetes treatments. We conducted a systematic search
      of clinical trials of the GLP-1 receptor agonists liraglutide, exenatide and long
      acting exenatide, one of which included the oral DPP-4 inhibitor sitagliptin as a
      comparator. No other PRO data for DPP-4 inhibitors were identified. This review
      summarizes PRO data from eight clinical trials, the majority of which used the
      Diabetes Treatment Satisfaction Questionnaire (DTSQ) and/or Impact of Weight on
      Quality of Life-Lite (IWQOL-Lite) to evaluate patient experience. People with
      T2DM were highly satisfied with modern incretin-based therapies compared with
      traditional therapies. Treatment satisfaction (including perceptions of
      convenience and flexibility) was high and generally higher with GLP-1 agonists in
      association with their greater glucose-lowering efficacy and tendency to
      facilitate weight loss. Weight-related quality of life (QoL) also improved in
      people using incretin therapies. The glycaemic improvements achieved with GLP-1
      receptor agonists, coupled with the low incidence of hypoglycaemia and ability to
      cause weight loss, seemed to offset potential concern about injections. It is
      plausible that superior patient-reported benefits found in clinical trials may
      translate into improved, clinically meaningful, long-term outcomes through
      increased treatment acceptability. Long-term, prospective data are needed to
      ascertain whether this is the case in practice.

PMID- 22420870
TI  - Impact of local and systemic alendronate on simvastatin-induced new bone around
      periodontal defects.
AB  - BACKGROUND: Simvastatin has been shown to stimulate new bone growth on rat
      mandibles, but much of the bone is lost over time. The purpose of this study is
      to evaluate the impact of a locally or systemically applied antiresorptive agent
      (alendronate) on simvastatin-induced bone formation in and adjacent to a rat
      periodontal defect. METHODS: Fenestration defects were created over mandibular
      molar roots in 65 mature female Sprague-Dawley rats. Two weeks later, animals
      were divided into eight groups of eight to nine rats, and three weekly injections
      around the defect were applied: 1) 0.5 mg simvastatin in ethanol (SIM-EtOH); 2)
      0.5 mg simvastatin in alendronate-cyclodextrin conjugate (SIM-ALN-CD); 3) EtOH
      alone; 4) ALN-CD alone; or 5) no injections. Twenty-four animals were evaluated
      for new bone width around the defect 21 days after the last injections (short
      term) and 41 rats were followed for 48 days (long-term). Three SIM-EtOH groups of
      long-term rats also were subjected to 2 weeks of daily systemic ALN or saline
      either during or 3 to 4 weeks after SIM-EtOH injections. Decalcified, hematoxylin
      and-eosin-stained cross-sections of the defect area were analyzed for new bone
      width and groups were compared using mixed-model analyses of variance. RESULTS:
      All groups showed nearly 100% bone fill, with no differences among the short-term
      groups. However, in the long-term animals, two-fold to three-fold more new bone
      width (<= 0.004) was seen around the periphery of the defect with the use of
      systemic ALN after SIM-EtOH injections (0.93 +/- 0.12 and 0.78 +/- 0.11 mm with
      early and late systemic ALN, respectively) compared to local SIM/ALN-CD
      preparations (0.32 +/- 0.10 mm) or short-term SIM-EtOH injections (0.35 +/- 0.10
      mm). No significant new cementum formation or ankylosis was noted. CONCLUSION:
      The use of a short course of systemic ALN during the healing period after bone
      anabolic SIM injections has the potential to enhance local bone augmentation.

PMID- 22420871
TI  - Efficacy of subgingivally delivered simvastatin in the treatment of patients with
      type 2 diabetes and chronic periodontitis: a randomized double-masked controlled
      clinical trial.
AB  - BACKGROUND: Simvastatin (SMV) is a specific competitive inhibitor of 3-hydroxy-2
      methyl-glutaryl coenzyme A reductase. Recently, it has been reported that statins
      promote bone formation. The present study is designed to investigate the
      effectiveness of 1.2% SMV in an indigenously prepared, biodegradable, controlled
      release gel as an adjunct to scaling and root planing (SRP) in the treatment of
      patients with type 2 diabetes and chronic periodontitis (CP). METHODS: Thirty
      eight patients were categorized into two treatment groups: SRP plus 1.2% SMV and
      SRP plus placebo. Clinical parameters were recorded at baseline before SRP and at
      3, 6, and 9 months; they included modified sulcus bleeding index (mSBI), probing
      depth (PD), and clinical attachment level (CAL). At baseline and after 6 and 9
      months, radiologic assessment of intrabony defect (IBD) fill was done using
      computer-aided software. RESULTS: Mean PD reduction and mean CAL gain were found
      to be greater in the SMV group than the placebo group at 3, 6, and 9 months.
      Furthermore, significantly greater mean percentage of bone fill was found in the
      SMV group (32.64% +/- 12.90%) compared to the placebo group (4.22% +/- 9.75%)
      after 9 months. CONCLUSION: There was a greater decrease in mSBI and PD and more
      CAL gain with significant IBD fill at sites treated with SRP plus locally
      delivered SMV in patients with type 2 diabetes and CP.

PMID- 22420873
TI  - Update of the case definitions for population-based surveillance of
      periodontitis.
AB  - BACKGROUND: This report adds a new definition for mild periodontitis that allows
      for better descriptions of the overall prevalence of periodontitis in
      populations. In 2007, the Centers for Disease Control and Prevention in
      partnership with the American Academy of Periodontology developed and reported
      standard case definitions for surveillance of moderate and severe periodontitis
      based on measurements of probing depth (PD) and clinical attachment loss (AL) at
      interproximal sites. However, combined cases of moderate and severe periodontitis
      are insufficient to determine the total prevalence of periodontitis in
      populations. METHODS: The authors proposed a definition for mild periodontitis as
      >= 2 interproximal sites with AL >= 3 mm and >= 2 interproximal sites with PD >=
      4 mm (not on the same tooth) or one site with PD >= 5 mm . The effect of the
      proposed definition on the total burden of periodontitis was assessed in a
      convenience sample of 456 adults >= 35 years old and compared with other
      previously reported definitions for similar categories of periodontitis. RESULTS:
      Addition of mild periodontitis increases the total prevalence of periodontitis by
      ~31% in this sample when compared with the prevalence of severe and moderate
      disease. CONCLUSION: Total periodontitis using the case definitions in this study
      should be based on the sum of mild, moderate, and severe periodontitis.

PMID- 22420874
TI  - Evaluation of the effects of buccal-palatal bone width on the incidence and
      height of the interproximal papilla between adjacent implants in esthetic areas.
AB  - BACKGROUND: The presence of interproximal papilla depends on the distance between
      the contact point to the bone crest, as well as the mesio-distal distance between
      implants or between implants and teeth. The aim of this study is to evaluate the
      effects of buccal-palatal bone width on the presence of the interproximal papilla
      between adjacent implants in esthetic areas of the mouth. METHODS: The presence
      or absence of the gingival papilla, distance from the base of the interproximal
      contact to the tip of the gingival papilla (black space), distance from the base
      of the interproximal contact to the alveolar crest (vertical distance), alveolar
      bone width (bone width) between adjacent implants as well as the spacing between
      the implants (horizontal distance), and soft-tissue biotype were assessed in 29
      interimplant areas in the upper incisor, canine, and premolar regions of 18
      patients. RESULTS: The papilla was always present when vertical distance was <=5
      mm (P <=0.04) and frequently present when the horizontal distance was >=4 mm (P =
      0.04). The black space was smaller when the vertical distance was <=5 mm (P
      <=0.04) and when the horizontal distance was >=4 mm (P = 0.76). Bone width and
      soft-tissue biotype did not influence the incidence of gingival papilla (P
      >=0.41) and black space (P >=0.15). CONCLUSION: Within the limits of this study,
      it can be concluded that bone width and tissue biotype do not have an effect on
      the incidence and height of papilla between adjacent implants in esthetic areas,
      and the incidence was greater when vertical distance was <=5 mm or when
      horizontal distance was >=4 mm.

PMID- 22420875
TI  - Host-bacterial interactions during induction and resolution of experimental
      gingivitis in current smokers.
AB  - BACKGROUND: Changes in clinical profiles, microbial succession, and immune
      mediator fluctuations have all been separately examined during onset and
      resolution of experimental gingivitis in smokers. However, because both the
      bacterial challenge and the host response contribute to periodontal disease, the
      purpose of this investigation is to simultaneously examine clinical, bacterial,
      and immune changes that occur during the onset and resolution of disease in
      smokers. METHODS: Experimental gingivitis was induced in 15 smokers for 21 days,
      followed by treatment with a sonic toothbrush for 21 days. Marginal and
      subgingival plaque and gingival crevicular fluid samples were collected at
      baseline; after 7, 14, and 21 days of undisturbed plaque formation; and 21 days
      after reinstitution of brushing. 16S cloning and sequencing was used for
      bacterial quantification, and multiplexed bead-based flow cytometry was used to
      quantify the levels of 27 immune mediators. RESULTS: Onset of clinical gingivitis
      was preceded by significant changes in the marginal and subgingival biofilms,
      with a decrease in the abundance of early colonizers, namely, Streptococcus,
      Veillonella, and Pseudomonas, and an increase in levels of periodontopathogens,
      such as Treponema, Selenomonas, Parvimonas, Dialister, and Campylobacter. This
      was accompanied by a decrease in anti-inflammatory, chemokine, and T-helper 2
      (Th2) responses and altered Th1/Th2 ratios. Although the bacterial communities
      continued to shift in the same direction after onset of clinical gingivitis and
      returned to baseline levels after resolution of disease, the anti-inflammatory,
      chemokine, and Th2 profiles demonstrated an increase from day 14 that continued
      even after clinical health was evident. CONCLUSION: Both marginal and subgingival
      biofilms in smokers are characterized by early acquisition of pathogenic
      organisms, which elicit a sustained host response that persists even after
      removal of the bacterial challenge.

PMID- 22420876
TI  - Toothbrushing education via a smart software visualization system.
AB  - BACKGROUND: The aim of this study is to evaluate the efficiency of a recently
      developed smart digital toothbrush monitoring and training system (DTS) in terms
      of correct brushing motion and grip axis orientation in an at-home environment.
      METHODS: Twenty-one participants (11 test individuals [DTSG] and 10 control
      individuals [COG]) received instructions on the modified Bass technique (MBT)
      after their toothbrushing performance was monitored and they received
      professional tooth cleaning (T0). After 36 hours (T1), without mechanical oral
      hygiene measures, plaque and gingival indices were recorded, and the brushing
      technique was reviewed. After randomization, participants individually performed
      oral hygiene for 6 weeks (T2) with the provided oral hygiene kits. The DTSG group
      additionally used DTS. During the following 8 weeks (T3), participants used their
      original brushing devices without any additional interference. Investigators at
      each visit were masked regarding group identity. Data were statistically
      evaluated using Mann-Whitney U, Friedman, Wilcoxon, and paired tests and Pearson
      correlation. RESULTS: At T0, 27.27% of DTSG participants used the MBT correctly
      (COG, 50%), increasing to 54.55% (COG, 60%) after professional instruction (T1)
      and further to 90.91% at T2 (COG, 60%) (P <0.001). Plaque scores were reduced in
      DTSG (P <0.05). At T3, 80% of the DTSG (COG, 40%) totally adopted the MBT (P
      <0.05). The plaque scores on buccal surfaces of the DTSG showed an additional
      slight improvement between T2 and T3, in contrast to a decline on oral surfaces
      (P <0.001). At T2 and T3, the DTSG brushed >120 seconds (COG, 90% and 50%) (P
      <0.05). CONCLUSION: Apparently, the tested DTS effectively improves the brushing
      technique and leads to a prolonged learning effect, including improved oral
      hygiene.

PMID- 22420877
TI  - Patents on quorum quenching: interfering with bacterial communication as a
      strategy to fight infections.
AB  - Numerous bacterial functions, such as virulence and biofilm formation, are
      controlled by a cell densitydependent communication mechanism known as Quorum
      Sensing (QS), in which small diffusible molecules are released, allowing bacteria
      to coordinate their behavior once a minimal effective quorum has been reached.
      The interference with these signaling systems, also known as Quorum Quenching
      (QQ), represents a promising strategy to tackle bacterial infections. The growing
      interest in this approach is reflected by the increasing number of patents within
      the field (45 up to now), especially in the last few years, as shown by patent
      applications published since 2009. The fact that biofilm formation is also
      controlled by QS systems expands the application of QQ to clinically-relevant
      biofilms such as those responsible for periodontal disease. Moreover, since
      biofilms increase bacterial resistance to antimicrobials, QQ could represent a
      new way to fight some of the most recurrent human pathogens, such as nosocomial
      multiresistant strains, and this deserves further exploration, especially through
      more proofs of concept. In this article we review the best known QS and QQ
      systems to date and we describe recent patents on the interference with this type
      of bacterial communication.

PMID- 22420878
TI  - Biofilms: new ideas for an old problem.
AB  - Microbial cells, under moist conditions, are able to adhere to surfaces and to
      form structured communities embedded in a matrix of extracellular polymeric
      substances (EPS). In industrial environments, biofilms can cause heat and mass
      transfer limitations whilst in medical facilities they can be a source of
      contamination and proliferation of infections. Biofilm formation is related to
      the pathogenicity of some bacterial strains and cells in biofilms are usually
      resistant to antimicrobials agents, which increases the interest in new and sound
      methods for their prevention and destruction.

PMID- 22420879
TI  - Effect of environmental conditions on the expression levels of a recombinant 11S
      amaranth globulin in Escherichia coli.
AB  - The expression in Escherichia coli strain Rosetta of the recombinant acidic
      subunit from the 11S amaranth seed storage protein (protein ACM3) was studied at
      flask and at bioreactor levels. This subunit was modified by inserting four Val
      Tyr antihypertensive peptides in tandem into its third variable region and also
      with the tripeptide Ile-Pro-Pro in the Cterminal region. Flasks experiments
      allowed us to define the best conditions for the preparation and expression and
      accumulation of the protein ACM3, including the certainty of its presence within
      the cells especially as an insoluble fraction. The effects of cultivation
      temperature, aeration rate and agitation speed on the production of the protein
      ACM3 was tested in a 5-L batch bioreactor. Applying response surface methodology
      (RSM) we found that the aeration rate was the most significant factor affecting
      in a positively way the production yields and productivity of the recombinant
      protein. Temperature had effect only in conjunction to aeration. The highest
      recombinant acidic subunit concentration (747 mg L-1) and the highest
      productivity (186 mg L-1 h-1) were attained in 4 h of cultivation when the
      factors evaluated were controlled at its central values: 0.1 vvm, 300 rpm, and
      30.5 degrees  C. Results from this study indicate that RSM is an effective
      technique to maximize the production of this recombinant protein.

PMID- 22420880
TI  - Laboratory dialysis--past, present and future.
AB  - Laboratory dialysis, one of the most widely used techniques in biological
      research is truly a ' gateway technology' . The analogy is to that of a ' gate' 
      of a building through which everybody has to pass, even though they may wish to
      go to different departments. Similarly, researchers may be working in altogether
      different areas but all may need to use laboratory dialysis at one stage or the
      other during the course of their research. Biochemists may use it to purify
      enzymes, an immunologist may use it to purify monoclonal antibodies from culture
      supernatants, a chemist may use it as a step in the crystallography process or
      for purification of ionic liquids, a biotechnologist may use it to study the
      effectiveness of enzyme immobilization and a drug discovery scientist may use it
      for determining drug-protein interaction. The present article reviews patents in
      the field of laboratory dialysis from inception till date, focusing on the
      various developmental and innovation related milestones during evolution of the
      technique. It captures the full panorama of a very interesting technique which
      continues to be as relevant today as it was in 1866 when the term ' dialysis' 
      was first coined.

PMID- 22420881
TI  - Monoclonal antibodies as cancer therapeutics.
AB  - Three main targets were subjected for the most approved monoclonal antibodies
      (mAbs) in cancer therapy: EGFR in solid cancer, the clusters of differentiation
      in blood cancer and VEGF in angiogenesis. Meanwhile side effects, the elevated
      costs and resistance problems are limiting the efficiency of mAbs as targeted
      therapy. The combinatory therapy with chemo or radiotherapy has improved the
      efficiency of mAbs. The present review aims to shed more light on the
      immunotherapy and the related patents that were developed for cancer treatment.

PMID- 22420882
TI  - Non-chromatographic strategies for protein refolding.
AB  - Overexpression of recombinant proteins in bacterial systems (such as E. coli)
      often leads to formation of inactive and insoluble ' inclusion bodies' . Protein
      refolding refers to folding back the proteins after solubilizing/unfolding the
      misfolded proteins of the inclusion bodies. Protein aggregation, a concentration
      dependent phenomenon, competes with refolding pathway. The refolding strategies
      largely aim at reducing aggregation and/or promoting correct folding. This review
      focuses on non-chromatographic strategies for refolding like dilution,
      precipitation, three phase partitioning and macro-(affinity ligand) facilitated
      three phase partitioning. The nanomaterials which disperse well in aqueous
      buffers are also discussed in the context of facilitating protein refolding.
      Apart from general results with these methods, the review also covers the use of
      non-chromatographic methods in protein refolding in the patented literature
      beyond 2000. The patented literature generally describes use of cocktail of
      additives which results in increase in refolding yield. Such additives include
      low concentration of chaotropic agents, redox systems, ions like SO4(2-) and Cl-,
      amines, carboxylic acids and surfactants. Some novel approaches like use of a
      "pressure window" or ionic liquids for refolding and immobilized diselenide
      compounds for ensuring correct -S-S- bonds pairing have also been discussed in
      various patents. In most of the patented literature, focus naturally has been on
      refolding in case of pharmaceutical proteins.

PMID- 22420883
TI  - Application of novel nanotechnology strategies in plant biotransformation: a
      contemporary overview.
AB  - During the past epoch we have gone through the remarkable progress in plant gene
      transformation technology. The production of transgenic plants is considered as a
      valuable tool in plant research and the technology is extensively applied in
      phytomedicines and agricultural research. Gene transformation in plants is
      normally carried out by Agrobacterium species, application of some chemicals and
      physical techniques (electroporation, microprojectile, etc.). Now a days with
      better efficacy and reproducibility, novel technologies for the direct gene
      transfer like liposome, positively charged liposome (lipofectin) and nanoparticle
      based delivery systems are used for genetic transformation of plants. In this
      review, we have enlightened the novel nanotechnologies like liposome, Carbon nano
      tube and nanoparticles with their current status and future prospects in
      transgenic plant development. Moreover, we have also highlighted the limitations
      of conventional techniques of gene transfer. Furthermore, we have tried to
      postulate innovative ideas on the footprints of established nanotechnology and
      chemical based strategy with improved efficacy, reproducibility and accuracy
      along with less time consumption.

PMID- 22420884
TI  - Application of the bicyclo[1.1.1]pentane motif as a nonclassical phenyl ring
      bioisostere in the design of a potent and orally active gamma-secretase
      inhibitor.
AB  - Replacement of the central, para-substituted fluorophenyl ring in the gamma
      secretase inhibitor 1 (BMS-708,163) with the bicyclo[1.1.1]pentane motif led to
      the discovery of compound 3, an equipotent enzyme inhibitor with significant
      improvements in passive permeability and aqueous solubility. The modified
      biopharmaceutical properties of 3 translated into excellent oral absorption
      characteristics (~4-fold ? C(max) and AUC values relative to 1) in a mouse model
      of gamma-secretase inhibition. In addition, SAR studies into other fluorophenyl
      replacements indicate the intrinsic advantages of the bicyclo[1.1.1]pentane
      moiety over conventional phenyl ring replacements with respect to achieving an
      optimal balance of properties (e.g., gamma-secretase inhibition, aqueous
      solubility/permeability, in vitro metabolic stability). Overall, this work
      enhances the scope of the [1.1.1]-bicycle beyond that of a mere "spacer" unit and
      presents a compelling case for its broader application as a phenyl group
      replacement in scenarios where the aromatic ring count impacts physicochemical
      parameters and overall drug-likeness.

PMID- 22420885
TI  - Adaptive immunity rather than viral cytopathology mediates polyomavirus
      associated nephropathy in mice.
AB  - Nephropathy associated with BK polyomavirus causes kidney allograft dysfunction
      and failure. Understanding the pathogenesis of polyomavirus-associated allograft
      nephropathy (PVAN) is hampered by the species specificity of Polyomaviridae
      family members. Using a mouse polyomavirus (MPyV) kidney transplant model, we
      investigated clinically relevant variables that may contribute to PVAN. We found
      that the timing and source (i.e. donor vs. recipient) of MPyV infection and the
      titer of the viral inoculum have significant effects on the extent of allograft
      injury, with acute infection of the recipient by high-titer MPyV inoculums
      producing the most profound PVAN. In contrast, altering the degree of MHC
      matching or increasing ischemia/reperfusion injury by prolonging the cold
      ischemic time of the allograft did not affect the severity of PVAN. Survival
      correlated positively with serum creatinine levels, but not with viral loads in
      the kidney allograft. Using splenectomized alymphoplasia mice, which are unable
      to mount primary adaptive immune responses, we further demonstrate that
      persistent high viral loads in the kidney are not sufficient to cause advanced
      PVAN. These findings suggest that the mechanism of PVAN in mice is not a direct
      consequence of viral cytopathology, but rather involves interplay between viral
      infection and the recipient antidonor immune response.

PMID- 22420886
TI  - Allele-specific primer polymerase chain reaction for a single nucleotide
      polymorphism (C1205T) of swine toll-like receptor 5 and comparison of the allelic
      frequency among several pig breeds in Japan and the Czech Republic.
AB  - In the present study, an allele-specific primer-polymerase chain reaction (ASP
      PCR) for genotyping a single nucleotide polymorphism (SNP) of swine Toll-like
      receptor 5 (TLR5) (C1205T; P402L) that is related to the impaired recognition of
      Salmonella enterica serovar Choleraesuis (SC) was developed. The allele
      frequencies in several pig breeds in Japan and the Czech Republic were also
      compared. The swine TLR5 C1205T mutation was successfully determined by ASP-PCR
      using genomic DNA samples in Japan that had previously been genotyped by a
      sequencing method. Using the PCR condition determined, genomic DNA samples from
      blood obtained from 110 pigs from seven different breeds in the Czech Republic
      were genotyped by the ASP-PCR. The genotyping results from the ASP-PCR completely
      matched the results from the sequencing method. The allele frequency of the swine
      TLR5 C1205T mutation was 27.5% in the Landrace breed of the Czech Republic
      compared with 50.0% in Japanese Landrace. In Japan, the C1205T mutation was found
      only in the Landrace breed, whereas in the Czech Republic it was found in both
      the Landrace and Pietrain breeds. These results indicate the usefulness of ASP
      PCR for detecting a specific SNP for swine TLR5 affecting ligand recognition.
      They also suggest the possibility of genetically improving pigs to enhance their
      resistance against SC infection by eliminating or selecting this specific SNP of
      swine TLR5.

PMID- 22420887
TI  - Rasch validation and predictive validity of the action research arm test in
      patients receiving stroke rehabilitation.
AB  - OBJECTIVE: To validate the internal construct and predictive validity of the
      Action Research Arm Test (ARAT). DESIGN: Secondary study. SETTING: Seven medical
      centers. PARTICIPANTS: Patients with stroke (N=191). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURE: The internal construct validity of the ARAT
      score at pretreatment was examined using Rasch analysis. The predictive validity
      was examined by the correlations between performance on the ARAT before treatment
      and scores on the Wolf Motor Function Test, the Motor Activity Log, and the
      Stroke Impact Scale after treatment. RESULTS: The 4-point ARAT scale had a
      disordered rating scale structure. Further Rasch modeling suggested revising the
      original 4-point scale into a 3-point scale. The 19 items measured 1 construct.
      The item difficulty hierarchy indicated that excluding the gross subtest, a score
      of 3 on the first item of any other subtest indicated the highest motor ability,
      and a score of 1 (the revised lowest rating) on the second item indicated the
      lowest motor ability. Tasks of "place hand behind head" and "place hand on top of
      head" showed poor item fit and item bias relevant to participants' ages. The ARAT
      items can reliably separate participants into 5.44 strata. Moderate to good
      correlations indicated good predictive validity. CONCLUSIONS: The ARAT possesses
      good psychometric properties in stroke patients with mild to moderate motor
      severity and without severe cognitive impairment, and has evidence of
      unidimensionality, predictive validity, and reliability. The revised 3-point
      rating scale is recommended when the ARAT is administered on this population. The
      "place hand behind head" and "place hand on top of head" tasks misfit the Rasch
      model's expectations. Future studies are needed in the use of the ARAT on stroke
      patients with different levels of motor severity or with cognitive impairment.

PMID- 22420888
TI  - Cross-validation of brain structural biomarkers and cognitive aging in a
      community-based study.
AB  - BACKGROUND: Population-based studies face challenges in measuring brain structure
      relative to cognitive aging. We examined the feasibility of acquiring state-of
      the-art brain MRI images at a community hospital, and attempted to cross-validate
      two independent approaches to image analysis. METHODS: Participants were 49 older
      adults (29 cognitively normal and 20 with mild cognitive impairment (MCI)) drawn
      from an ongoing cohort study, with annual clinical assessments within one month
      of scan, without overt cerebrovascular disease, and without dementia (Clinical
      Dementia Rating (CDR) < 1). Brain MRI images, acquired at the local hospital
      using the Alzheimer's Disease Neuroimaging Initiative protocol, were analyzed
      using (1) a visual atrophy rating scale and (2) a semi-automated voxel-level
      morphometric method. Atrophy and volume measures were examined in relation to
      cognitive classification (any MCI and amnestic MCI vs. normal cognition), CDR
      (0.5 vs. 0), and presumed etiology. RESULTS: Measures indicating greater atrophy
      or lesser volume of the hippocampal formation, the medial temporal lobe, and the
      dilation of the ventricular space were significantly associated with cognitive
      classification, CDR = 0.5, and presumed neurodegenerative etiology, independent
      of the image analytic method. Statistically significant correlations were also
      found between the visual ratings of medial temporal lobe atrophy and the semi
      automated ratings of brain structural integrity. CONCLUSIONS: High quality MRI
      data can be acquired and analyzed from older adults in population studies,
      enhancing their capacity to examine imaging biomarkers in relation to cognitive
      aging and dementia.

PMID- 22420889
TI  - Relation of total and free testosterone and sex hormone-binding globulin with
      cardiovascular risk factors in men aged 24-45 years. The Cardiovascular Risk in
      Young Finns Study.
AB  - BACKGROUND: Total and free testosterone decrease gradually in men with advancing
      age but it is not completely known how lower levels of testosterone are related
      with various cardiovascular risk factors. We studied the levels of total
      testosterone, calculated free testosterone and sex hormone-binding globulin
      (SHBG), and their relations with cardiovascular risk factors in young Finnish
      men. METHODS: The study cohort consisted of 24-45-year-old men participating the
      Cardiovascular Risk in Young Finns Study in the follow-up surveys performed in
      2001 (N=1024) and 2007 (N=991). Levels of total testosterone, SHBG, lipids,
      glucose, insulin, blood pressure and anthropometric factors were measured and
      free testosterone was calculated. RESULTS: In multivariable analyses adjusted for
      age, body mass index and life-style factors (alcohol consumption, smoking and
      physical activity), total and calculated free testosterone were inversely
      correlated with triglycerides (both P<0.0001), insulin (P=0.0004 and P=0.01),
      systolic blood pressure (P=0.007 and P=0.01), and directly with high-density
      lipoprotein (HDL) cholesterol (P<0.0001 and P=0.003). SHBG was inversely
      correlated with triglycerides and insulin, and directly with HDL-cholesterol (all
      P<0.001). In longitudinal analyses, lower levels of testosterone and SHBG were
      associated with higher levels of triglycerides and insulin six years later (all
      P<0.01). Baseline level of SHBG was directly associated with HDL-cholesterol
      (P<0.0001). CONCLUSION: In young and middle-aged men, higher levels of
      testosterone and SHBG are associated with favourable cardiovascular risk profile
      characterized by lower levels of triglycerides, insulin and systolic blood
      pressure, and higher levels of HDL-cholesterol.

PMID- 22420890
TI  - FABP4 predicts atherogenic dyslipidemia development. The PREDIMED study.
AB  - OBJECTIVE: Atherogenic dyslipidemia (AD), characterized by high plasma
      triglycerides and low HDL particles, is considered one of the main effectors of
      vascular damage associated with obesity, metabolic syndrome (MS) and type 2
      diabetes. Adipocyte fatty acid-binding protein (FABP4) plasma concentrations have
      been linked to metabolic alterations that are associated with adiposity. The aim
      of the present study was to prospectively analyze the predictive value of
      baseline FABP4 plasma concentrations for the development of AD. METHODS: In the
      frame of the PREDIMED study, a multicenter dietary interventional trial, we
      prospectively measured the baseline plasma FABP4 levels and AD incidence over a
      six-year follow-up period (median 4 [IQR, 3-5 years]) in 578 volunteers who
      visited their general practitioners because of their cardiovascular risk factors.
      RESULTS: During follow-up, 103 participants developed AD. Baseline plasma FABP4
      levels were associated with new onset AD over the follow-up period (OR 1.03 [95%
      IC: 1.00-1.05], p=0.020). This increased risk was observed in women but not in
      men. Among women, those in the highest tertile of FABP4 had a 2.54-fold increased
      relative risk of developing AD compared to the lowest tertile (HR 2.54 [95% CI,
      1.31-4.93], p for trend=0.008). CONCLUSIONS: Elevated plasma FABP4 concentrations
      should be considered as a potential marker of metabolic derangement, which may
      predict the development of AD in women.

PMID- 22420891
TI  - Associations between alcohol consumption and selected cytokines in a Swiss
      population-based sample (CoLaus study).
AB  - OBJECTIVE: To assess the associations between alcohol consumption and cytokine
      levels (interleukin-1beta - IL-1beta; interleukin-6 - IL-6 and tumor necrosis
      factor-alpha - TNF-alpha) in a Caucasian population. METHODS: Population sample
      of 2884 men and 3201 women aged 35-75. Alcohol consumption was categorized as
      nondrinkers, low (1-6 drinks/week), moderate (7-13/week) and high (14+/week).
      RESULTS: No difference in IL-1beta levels was found between alcohol consumption
      categories. Low and moderate alcohol consumption led to lower IL-6 levels: median
      (interquartile range) 1.47 (0.70-3.51), 1.41 (0.70-3.32), 1.42 (0.66-3.19) and
      1.70 (0.83-4.39) pg/ml for nondrinkers, low, moderate and high drinkers,
      respectively, p<0.01, but this association was no longer significant after
      multivariate adjustment. Compared to nondrinkers, moderate drinkers had the
      lowest odds (Odds ratio=0.86 (0.71-1.03)) of being in the highest quartile of IL
      6, with a significant (p<0.05) quadratic trend. Low and moderate alcohol
      consumption led to lower TNF-alpha levels: 2.92 (1.79-4.63), 2.83 (1.84-4.48),
      2.82 (1.76-4.34) and 3.15 (1.91-4.73) pg/ml for nondrinkers, low, moderate and
      high drinkers, respectively, p<0.02, and this difference remained borderline
      significant (p=0.06) after multivariate adjustment. Moderate drinkers had a lower
      odds (0.81 [0.68-0.98]) of being in the highest quartile of TNF-alpha. No
      specific alcoholic beverage (wine, beer or spirits) effect was found.
      CONCLUSIONS: Moderate alcohol consumption is associated with lower levels of IL-6
      and (to a lesser degree) of TNF-alpha, irrespective of the type of alcohol
      consumed. No association was found between IL-1beta levels and alcohol
      consumption.

PMID- 22420892
TI  - Low rate of detection of active cytomegalovirus (CMV) infection early following
      acute myocardial infarction.

PMID- 22420893
TI  - Prognostic value of reverse left ventricular remodeling after primary angioplasty
      for STEMI.
AB  - AIMS: Thus far, the prognostic value of reverse left ventricular (LV) remodeling
      after ST-elevation acute myocardial infarction (STEMI) has not been fully
      evaluated. We sought to investigate the incidence, major determinants, and long
      term clinical significance of reverse LV remodeling in a large series of STEMI
      patients successfully treated with primary percutaneous coronary intervention (P
      PCI). METHODS AND RESULTS: Serial complete 2D-echocardiograms were obtained
      within 24h after P-PCI, and at 1 and 6 months in 512 consecutive reperfused STEMI
      patients. Reverse remodeling was defined as a reduction >10% in LV end-systolic
      volume (LVESV) at 6 month follow-up. Reverse LV remodeling occurred in 49% of
      study population. At follow-up (41.6+/-23 months), late heart failure (HF) rate
      was significantly higher among patients without reverse LV remodeling as compared
      with those with it (32% vs. 11%, P<0.0001). At multivariate analysis, independent
      predictors of reverse LV remodeling were a small infarct size measured as peak
      creatine kinase value (P<0.0001), a small functional myocardial damage measured
      as wall motion score index within the infarct zone (P=0.018) and baseline LVESV
      (P<0.0001). After adjustment for several clinical, echographic and angiographic
      variables, Cox analysis identified reverse LV remodeling as the only beneficial
      independent predictor of long-term heart failure-free survival (HR: 0.44, 95% CI:
      0.275-0.722). CONCLUSIONS: Reverse LV remodeling occurred in half of successfully
      reperfused STEMI patients. Small structural and functional myocardial damages
      within the infarct zone are the major determinants of reverse LV remodeling. As
      expression of effective myocardial salvage by P-PCI, the reverse remodeling is an
      important predictor of favorable long-term outcome.

PMID- 22420894
TI  - Differential proteomic distribution of TTR (pre-albumin) forms in serum and HDL
      of patients with high cardiovascular risk.
AB  - Inflammation is a common condition contributing to cardiovascular disease
      progression which leads to clinical manifestations such as acute myocardial
      infarction (AMI). By applying a proteomic expression profiling approach we have
      investigated changes in transthyretin (TTR) in AMI-patients and its distribution
      patterns in HDL samples of patients with high cardiovascular risk, such as those
      with familiar hypercholesterolemia (FH). METHODS AND RESULTS: The
      characterization by bidimensional electrophoresis (2-DE), followed by mass
      spectrometry (MALDI-TOF) of serum samples revealed changes in the intensity of
      the TTR spot with a pI of 5.6 and a Mw of 42kDa (tTTR) between AMI-patients in
      association to diabetic dyslipemia. Serum TTR levels, determined by commercial
      ELISA, were significantly lower (p<0.0001) in AMI-patients (n=39) and FH-patients
      (n=100) than in healthy controls (n=60). Western blot and 2-DE analysis showed a
      differential distribution profile of TTR forms between serum, where 3 TTR forms
      of 42 (tTTR), 28 (dTTR), and 14kDa (mTTR) were detected, and HDL samples, where
      only mTTR was present. CONCLUSIONS: Our results demonstrate alterations in TTR
      proteomic profile in relation to the clustering of risk factors which seems to
      highlight the implication of TTR in cardiovascular risk. The significant
      differences in TTR between serum (tTTR) and HDL (mTTR) underscore the importance
      of TTR-forms in the circulation and deserve further investigation to understand
      their function.

PMID- 22420895
TI  - Oral mucosal hyperpigmentation and horizontal melanonychia caused by imatinib.

PMID- 22420896
TI  - Knockdown of the nucleosome binding protein 1 inhibits the growth and invasion of
      clear cell renal cell carcinoma cells in vitro and in vivo.
AB  - BACKGROUND: The nucleosome binding protein 1 (HMGN5/NSBP1) is a member of the
      HMGN protein family and is highly expressed in several kinds of cancer.
      Nevertheless, the role of NSBP1 in clear cell renal cell carcinoma (ccRCC)
      remains unclear. This study aimed to confirm the oncogenic role of NSBP1 in ccRCC
      using in vitro and in vivo models and explore the mechanism by which NSBP1
      contributes to ccRCC tumorigenesis. METHODS: NSBP1 expression was detected in
      renal tissues from 152 ccRCC patients by immunohistochemistry, and examined in
      ccRCC cell lines by RT-PCR and Western blot analysis. ccRCC cells were
      transfected by NSBP1 RNAi and cell viability, apoptosis and invasion were
      detected by cell vitality test, flow cytometry and transwell assay in vitro.
      Xenograft in nude mice was also employed to examine the tumorigenesis of ccRCC
      cells depleted of NSBP1. RESULTS: Immunohistostaining showed strong
      immunoreactivity of NSBP1 in all ccRCC tissues and NSBP1 expression level was
      associated with tumor grade (p = 0.04). NSBP1 expression at mRNA and protein
      levels was high in ccRCC cell lines. Knockdown of NSBP1 induced cell cycle arrest
      and apoptosis, and inhibited invasion in 786-O cells. Western blot analysis
      demonstrated increased expression of Bax and decreased expression of Bcl-2,
      CyclinB1, VEGF, VEGFR-2, MMP-2, MMP-9, c-fos and c-jun in 786-O cells depleted of
      NSBP1. In vivo study further showed that knockdown of NSBP1 affected the
      tumorigenesis of ccRCC cells in nude mice. CONCLUSIONS: NSBP1 plays oncogenic
      role in ccRCCs by promoting cell proliferation and invasion, and could be
      exploited as a target for ccRCC treatment.

PMID- 22420897
TI  - In vitro anti-myeloma activity of TRAIL-expressing adipose-derived mesenchymal
      stem cells.
AB  - Recently, genetically modified mesenchymal stem cells (MSCs) have been exploited
      to deliver anti-cancer bio-drugs directly within the tumour mass. Here, we
      explored whether adipose-derived MSCs (AD-MSCs), engineered to express the pro
      apoptotic ligand TRAIL (also known as TNFSF10), kill multiple myeloma (MM) cells
      and migrate towards MM cells in vitro. Different MM cell lines were assessed for
      their sensitivity to recombinant human (rh) TRAIL alone and in combination with
      the proteasome inhibitor bortezomib, which was shown to enhance the effect of
      rhTRAIL. TRAIL(+) -AD-MSCs were co-cultured with bortezomib-pretreated MM cells
      and their killing activity was evaluated in presence or absence of caspase
      inhibition. AD-MSC migration towards media conditioned by both myeloma cells and
      myeloma bone fragments was also investigated. Despite moderate MM cell
      sensitivity to rhTRAIL, TRAIL(+) -AD-MSCs in combination with bortezomib
      significantly induced myeloma cell death. This effect was associated with caspase
      8 activation and abrogated by capsase inhibition. On the other hand, co-culture
      experiments were performed to evaluate whether unmodified AD-MSCs affect myeloma
      cell growth in vitro. AD-MSCs appeared ineffective on myeloma cell growth and
      showed migratory capacity towards MM cells in vitro. These data emphasize the
      anti-myeloma activity of TRAIL-engineered AD-MSCs and provide support for a
      future model of a cell-based approach against MM.

PMID- 22420898
TI  - Multiple dot-in-rod PbS/CdS heterostructures with high photoluminescence quantum
      yield in the near-infrared.
AB  - Pb cations in PbS quantum rods made from CdS quantum rods by successive complete
      cationic exchange reactions are partially re-exchanged for Cd cations. Using STEM
      HAADF, we show that this leads to the formation of unique multiple dot-in-rod
      PbS/CdS heteronanostructures, with a photoluminescence quantum yield of 45-55%.
      We argue that the formation of multiple dot-in-rods is related to the initial
      polycrystallinity of the PbS quantum rods, where each PbS crystallite transforms
      in a separate PbS/CdS dot-in-dot. Effective mass modeling indicates that
      electronic coupling between the different PbS conduction band states is feasible
      for the multiple dot-in-rod geometries obtained, while the hole states remain
      largely uncoupled.

PMID- 22420900
TI  - Human herpesvirus 8 transfusion transmission in Ghana, an endemic region of West
      Africa.
AB  - BACKGROUND: Human herpesvirus 8 (HHV-8) seroprevalence ranges between less than
      5% in Europe and North America and 50% to 70% in sub-Saharan Africa. Evidence of
      HHV-8 transfusion transmission is only indirect. We conducted a serologic (anti
      HHV-8) and molecular (HHV-8 DNA) study of samples from paired donor
      immunocompetent recipients transfused with whole blood. STUDY DESIGN AND METHODS:
      Samples from 252 donor-recipient pairs were tested. Immunoglobulin G to HHV-8 was
      detected with enzyme immunoassays and confirmed with an in-house
      immunofluorescence assay. The cellular fraction from seroreactive donors and
      their recipients was tested for HHV-8 DNA. RESULTS: Anti-HHV-8 was positive
      (reactive in two or more assays) in 28 (11%) patients and 16 (6%) donors. Of 12
      seronegative recipients (at risk of transmission) receiving seropositive blood,
      one very likely transmission was identified (8.3% confidence interval, 0%-23%).
      The donor blood contained HHV-8 DNA and his and four other donors' sequences
      clustered separately from recorded genotypes with a 97% bootstrap constituting a
      distinct genotype. CONCLUSIONS: HHV-8 is transmitted in Ghana but does not carry
      clinical consequences since most patients are immunocompetent. The clinical risk
      will increase with the availability of immunosuppressive drugs in sub-Saharan
      Africa. We propose that a new genotype (HHV-8-G for Ghana) be added to the
      current nomenclature.

PMID- 22420899
TI  - Astrocytes convert network excitation to tonic inhibition of neurons.
AB  - BACKGROUND: Glutamate and gamma-aminobutyric acid (GABA) transporters play
      important roles in balancing excitatory and inhibitory signals in the brain.
      Increasing evidence suggest that they may act concertedly to regulate
      extracellular levels of the neurotransmitters. RESULTS: Here we present evidence
      that glutamate uptake-induced release of GABA from astrocytes has a direct impact
      on the excitability of pyramidal neurons in the hippocampus. We demonstrate that
      GABA, synthesized from the polyamine putrescine, is released from astrocytes by
      the reverse action of glial GABA transporter (GAT) subtypes GAT-2 or GAT-3. GABA
      release can be prevented by blocking glutamate uptake with the non-transportable
      inhibitor DHK, confirming that it is the glutamate transporter activity that
      triggers the reversal of GABA transporters, conceivably by elevating the
      intracellular Na+ concentration in astrocytes. The released GABA significantly
      contributes to the tonic inhibition of neurons in a network activity-dependent
      manner. Blockade of the Glu/GABA exchange mechanism increases the duration of
      seizure-like events in the low-[Mg2+] in vitro model of epilepsy. Under in vivo
      conditions the increased GABA release modulates the power of gamma range
      oscillation in the CA1 region, suggesting that the Glu/GABA exchange mechanism is
      also functioning in the intact hippocampus under physiological conditions.
      CONCLUSIONS: The results suggest the existence of a novel molecular mechanism by
      which astrocytes transform glutamatergic excitation into GABAergic inhibition
      providing an adjustable, in situ negative feedback on the excitability of
      neurons.

PMID- 22420901
TI  - Antioxidant and antiproliferative activities of anthocyanin/ellagitannin-enriched
      extracts from Syzygium cumini L. (Jamun, the Indian Blackberry).
AB  - Colored fruits, particularly berries, are highly chemoprotective because of their
      antioxidant, antiproliferative, and antiinflammatory activities. We report the
      cancer chemoprotective potential of Syzygium cumini L., commonly known as jamun
      or Indian blackberry. Anthocyanins and other polyphenolics were extracted with
      acidic ethanol and enriched by amberlite XAD7/HP20 (1:1). The pulp powder was
      found to contain 0.54% anthocyanins, 0.17% ellagic acid/ellagitannins, and 1.15%
      total polyphenolics. Jamun seed contained no detectable anthocyanins but had
      higher amounts of ellagic acid/ellagitannins (0.5%) and total polyphenolics
      (2.7%) than the pulp powder. Upon acid hydrolysis, the pulp extract yielded 5
      anthocyanidins by HPLC: malvidin (44.4%), petunidin (24.2%), delphinidin (20.3%),
      cyanidin (6.6%), and peonidin (2.2%). Extracts of both jamun pulp (1,445 +/- 64
      MUmol of trolox equivalent (TE)/g) and seeds (3,379 +/- 151 MUM of TE/g) showed
      high oxygen radical absorbance capacity. Their high antioxidant potential was
      also reflected by 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)- and 2,2
      diphenyl-1-picrylhydrazyl-scavenging and ferrous ion-chelating activities. We
      also analyzed antiproliferative activity of jamun extracts against human lung
      cancer A549 cells. The hydrolyzed pulp and seed extracts showed significant
      antiproliferative activity. However, unhydrolyzed extracts showed much less
      activity. These data showed that in addition to 5 anthocyanidins, jamun contains
      appreciable amounts of ellagic acid/ellagitannins, with high antioxidant and
      antiproliferative activities.

PMID- 22420902
TI  - Discovery of a novel HLA-B*51 variant, B*51:112, in a Taiwanese bone marrow donor
      and identification of the plausible HLA haplotype in association with B*51:112.
AB  - The sequence of B*51:112 is identical to the sequence of B*51:01:01 in exons 2, 3
      and 4, except the nucleotides at positions 206 (C->A) and 213 (C->G). The
      nucleotide replacement caused one amino acid substitution at residue 45 (T->K).
      The plausible HLA-A, -B and -DRB1 haplotype in association with B*51:112 may be
      deduced as HLA-A*02-B*51:112-DRB1*12. The generation of B*51:112 was probably as
      the result of a DNA recombination event where B*40:01:01 acted as a sequence
      donor donating a segment of the DNA sequence to the recipient sequence
      B*51:01:01. The donor carrying B*51:112 was a Minna Taiwanese whose ancestor came
      to Taiwan from the southern region of China.

PMID- 22420904
TI  - [Case 52. Pericecal hernia without intestinal obstruction].

PMID- 22420905
TI  - [Solution to case 51. Langerhans cell histiocytosis with early multisystemic
      involvement].

PMID- 22420908
TI  - Fixed-dose combinations for emerging treatment of pain.
AB  - INTRODUCTION: Pain is a large and growing medical need that is not currently
      being fully met, primarily due to the shortcomings of existing analgesics
      (insufficient efficacy or limiting side-effects). Better outcomes might be
      achieved using a combination of analgesics. The ratio of the combinations matters
      and should therefore be evaluated using rigorous quantitative and well-documented
      analysis. AREAS COVERED: Advances have been made in understanding the normal
      physiology of pain processing, including the pathways and neurotransmitters
      involved. Insight has also been gained about physiological processes that can
      lead to different 'types' of pain and the transition from acute to chronic pain
      conditions. This 'multimechanistic' nature of most pains is better matched using
      a 'multimechanistic' rather than 'monomechanistic' analgesic approach. Such an
      approach - and the experimental design and data analysis to assess optimal
      combinations - is described and discussed. EXPERT OPINION: There are sound
      pharmacologic, as well as practical, reasons for using combinations of drugs to
      treat pain. Compared with single agents, they offer a potential better match to
      the underlying pain physiology and thus greater efficacy or reduced side effects.
      The optimal efficacy and side-effect ratio must be determined in a scientifically
      rigorous manner.

PMID- 22420909
TI  - Stress ulcer prophylaxis in non-critically ill patients: a prospective evaluation
      of current practice in a general surgery department.
AB  - RATIONALE, AIMS AND OBJECTIVES: There is little evidence regarding the benefit of
      stress ulcer prophylaxis (SUP) outside a critical care setting. Overprescription
      of SUP is not devoid of risks. This prospective study aimed to evaluate the use
      of proton pump inhibitors (PPIs) for SUP in a general surgery department. METHOD:
      Data collection was performed prospectively during an 8-week period on patients
      hospitalized in a general surgery department (58 beds) by pharmacists. Patients
      with a PPI prescription for the treatment of ulcers, gastro-oesophageal reflux
      disease, oesophagitis or epigastric pain were excluded. Patients admitted twice
      during the study period were not reincluded. The American Society of Health
      System Pharmacists guidelines on SUP were used to assess the appropriateness of
      de novo PPI prescriptions. RESULTS: Among 255 patients in the study, 138 (54%)
      received a prophylaxis with PPI, of which 86 (62%) were de novo PPI
      prescriptions. A total of 129 patients (94%) received esomeprazole (according to
      the hospital drug policy). The most frequent dosage was at 40 mg once daily. Use
      of PPI for SUP was evaluated in 67 patients. A total of 53 patients (79%) had no
      risk factors for SUP. Twelve and two patients had one or two risk factors,
      respectively. At discharge, PPI prophylaxis was continued in 33% of patients with
      a de novo PPI prescription. CONCLUSIONS: This study highlights the overuse of
      PPIs in non-intensive care unit patients and the inappropriate continuation of
      PPI prescriptions at discharge. Treatment recommendations for SUP are needed to
      restrict PPI use for justified indications.

PMID- 22420910
TI  - Health, vital goals, and central human capabilities.
AB  - I argue for a conception of health as a person's ability to achieve or exercise a
      cluster of basic human activities. These basic activities are in turn specified
      through free-standing ethical reasoning about what constitutes a minimal
      conception of a human life with equal human dignity in the modern world. I arrive
      at this conception of health by closely following and modifying Lennart
      Nordenfelt's theory of health which presents health as the ability to achieve
      vital goals. Despite its strengths I transform Nordenfelt's argument in order to
      overcome three significant drawbacks. Nordenfelt makes vital goals relative to
      each community or context and significantly reflective of personal preferences.
      By doing so, Nordenfelt's conception of health faces problems with both socially
      relative concepts of health and subjectively defined wellbeing. Moreover,
      Nordenfelt does not ever explicitly specify a set of vital goals. The theory of
      health advanced here replaces Nordenfelt's (seemingly) empty set of preferences
      and society-relative vital goals with a human species-wide conception of basic
      vital goals, or 'central human capabilities and functionings'. These central
      human capabilities come out of the capabilities approach (CA) now familiar in
      political philosophy and economics, and particularly reflect the work of Martha
      Nussbaum. As a result, the health of an individual should be understood as the
      ability to achieve a basic cluster of beings and doings-or having the overarching
      capability, a meta-capability, to achieve a set of central or vital inter-related
      capabilities and functionings.

PMID- 22420911
TI  - Infant with "large right pupil" associated with suspected corneal enlargement.

PMID- 22420912
TI  - Pediatric ocular trauma.

PMID- 22420914
TI  - Botulinum toxin for the treatment of early-onset esotropia in children with
      cerebral palsy.

PMID- 22420915
TI  - Intravenous sodium fluorescein 10% for laser ablation of subtle retinal
      neovascularization in FEVR.

PMID- 22420916
TI  - Bilateral optic nerve head drusen.

PMID- 22420918
TI  - Commentary--collaborative evaluation within the larger evaluation context.

PMID- 22420917
TI  - The influence of regional health care structures on delay in diagnosis of rare
      diseases: the case of Marfan Syndrome.
AB  - INTRODUCTION: This study investigates the relative influence of the regional
      availability of health care resources (measured by physician densities, number of
      health care centers) on health care quality (measured by delay in diagnosis),
      based on data for the rare disease Marfan Syndrome. METHODS: Administrative data
      from 389 patients with Marfan Syndrome were analyzed. Logistic regression models
      were applied for a dichotomous comparison of the dependent variable 'time to
      diagnosis' with the classifications 'immediate' and 'late' diagnosis. Physician
      densities of cardiologists/angiologists, ophthalmologists, orthopedists, and GPs,
      as well as distance to medical health care centers and sociodemographic
      information were entered into the models. RESULTS: The results showed that the
      relationship between physician densities and probability of immediate diagnosis
      of Marfan Syndrome is negative linear, and quadratic for
      cardiologists/angiologists. This effect was significant with respect to density
      of cardiologists/angiologists (p=0.0097). Distance to medical health care centers
      was not a predictor of an immediate diagnosis. CONCLUSION: Marfan Syndrome faces
      significant problems of quality of health care, as although the requisite
      quantity of health care resources is available, this does not affect delay in
      diagnosis. Information technology might foster valuable networking among
      physicians treating such cases along with holistic assessment of symptoms as they
      occur.

PMID- 22420919
TI  - Microarray analysis of Etrog citron (Citrus medica L.) reveals changes in
      chloroplast, cell wall, peroxidase and symporter activities in response to viroid
      infection.
AB  - Viroids are small (246-401 nucleotides), single-stranded, circular RNA molecules
      that infect several crop plants and can cause diseases of economic importance.
      Citrus are the hosts in which the largest number of viroids have been identified.
      Citrus exocortis viroid (CEVd), the causal agent of citrus exocortis disease,
      induces considerable losses in citrus crops. Changes in the gene expression
      profile during the early (pre-symptomatic) and late (post-symptomatic) stages of
      Etrog citron infected with CEVd were investigated using a citrus cDNA microarray.
      MaSigPro analysis was performed and, on the basis of gene expression profiles as
      a function of the time after infection, the differentially expressed genes were
      classified into five clusters. FatiScan analysis revealed significant enrichment
      of functional categories for each cluster, indicating that viroid infection
      triggers important changes in chloroplast, cell wall, peroxidase and symporter
      activities.

PMID- 22420921
TI  - Immunity induced by Staphylococcus aureus surface protein A was protective
      against lethal challenge of Staphylococcus aureus in BALB/c mice.
AB  - Staphylococcus aureus is the most common cause of hospital-acquired bacteremia.
      Due to emergence of antibiotic-resistant strains, these infections present a
      serious public health threat. In this study, to develop a broadly protective
      vaccine, we tested whether immune responses induced by several proteins
      associated with S. aureus toxicity could protect mice from lethal challenge with
      human clinical S. aureus isolate USA300. We found that the surface protein A
      (SasA) of S. aureus could protect mice from lethal challenge of the bacteria.

PMID- 22420920
TI  - Human papillomavirus vaccine use among adolescent girls and young adult women: an
      analysis of the 2007 California Health Interview Survey.
AB  - BACKGROUND: Administration of the human papillomavirus (HPV) vaccine is
      recommended for adolescent girls and young adult women. Little is known about the
      factors associated with vaccination. This study examined prevalence and
      correlates of HPV vaccine initiation (>=1 dose) among a statewide representative
      sample of adolescent and young adult females living in California. METHODS: HPV
      vaccination data on 3615 parents of adolescent girls aged 12-17 and 2068 young
      adult women aged 18-27 from the 2007 California Health Interview Survey (CHIS)
      were examined by sociodemographic, healthcare access, and health behavior factors
      using chi-square and multivariable logistic regression models. RESULTS: Nineteen
      percent of adolescent girls and 11% of young adult women had initiated the HPV
      vaccine series. In both groups, lower educational attainment (parental/own) was
      associated with lack of vaccine initiation. For adolescents, vaccine initiation
      was also significantly lower among those whose parents had low incomes or no
      usual source of care. For young adults, initiation was lower among the older
      group and those who spent less time in the United States, had public insurance,
      had no recent provider visit, or had fewer sexual partners. CONCLUSIONS: In a
      statewide representative sample, different correlates of early initiation of HPV
      vaccination emerged for Californian adolescent girls and young adult women. These
      different patterns may be due to differential access to programs that provide
      free or low-cost HPV vaccines. Because several of these factors are associated
      with disparities in use of Pap tests, disparities will persist or even worsen
      unless greater effort is placed on vaccinating populations at highest risk for
      cervical cancer.

PMID- 22420923
TI  - Unknotting night-time muscle cramp: a survey of patient experience, help-seeking
      behaviour and perceived treatment effectiveness.
AB  - BACKGROUND: Night-time calf cramping affects approximately 1 in 3 adults. The aim
      of this study was to explore the experience of night-time calf cramp; if and
      where people seek treatment advice; and perceived treatment effectiveness.
      METHODS: 80 adults who experienced night-time calf cramp at least once per week
      were recruited from the Hunter region, NSW, Australia through newspaper, radio
      and television advertisements. All participants completed a pilot-tested survey
      about muscle cramp. Quantitative data were analysed with independent-sample t
      tests, Chi square tests and Fisher's tests. Qualitative data were transcribed and
      sorted into categories to identify themes. RESULTS: Median recalled age of first
      night-time calf cramp was 50 years. Most participants recalled being awoken from
      sleep by cramping, and experiencing cramping of either calf muscle, calf-muscle
      soreness in the days following cramp and cramping during day-time. Despite
      current therapies, mean usual pain intensity was 66 mm on a 100 mm visual
      analogue scale. Participants described their cramps as being 'unbearable',
      'unmanageable' and 'cruel'. One participant stated that 'sometimes I just wish I
      could cut my legs open' and another reported 'getting about 2 h sleep a night due
      to cramps'. Most participants had sought advice about their night-time calf
      cramps from a health professional. Participants identified 49 different
      interventions used to prevent night-time calf cramp. Of all treatment ratings,
      68% described the intervention used to prevent cramp as being 'useless' or of 'a
      little help'. Of 14 participants who provided additional information regarding
      their use of quinine, eight had a current prescription of quinine for muscle
      cramp at the time of the survey. None had been asked by their prescribing doctor
      to stop using quinine. CONCLUSION: Night time calf cramps typically woke
      sufferers from sleep, affected either leg and caused ongoing pain. Most
      participants experienced little or no relief with current therapies used to
      prevent muscle cramp. Most people who were taking quinine for muscle cramp were
      unaware that the Australian Therapeutic Goods Administration withdrew support of
      quinine for muscle cramp in 2004 due to the risk of thrombocytopaenia. Case
      control studies are required to identify therapeutic targets so that clinical
      trials can evaluate safe interventions to prevent recurrent cramp.

PMID- 22420924
TI  - An immunohistochemical study of HER2 expression in meningioma and its correlation
      with tumor grade.
AB  - Meningiomas account for about 15-30% of all primary intracranial tumors.
      According to the 2007 WHO classification, meningiomas are divided into three
      grades (I, II and III). Recurrence is an issue following surgical treatment of
      meningioma, especially in grades II and III. HER2 (also known as erbB-2) is a 185
      kD transmembrane glycoprotein with tyrosine kinase activity. HER2 is expressed in
      some human malignancies and can be a potential target for therapeutic
      intervention with selective inhibitors. There are only a few studies on the
      relationship between meningioma and HER2 expression, and the results are
      different as well. The aim of this study was to determine this relationship.
      Seventy-two paraffin blocks of meningioma were selected randomly, and
      immunohistochemical staining was then performed for each specimen. Thirty-one of
      the 72 meningiomas were HER2-positive. HER2 expression was observed in 11 (55%)
      of the 20 grade II/III, and 20 (38.5%) of the 52 grade I meningiomas.
      Consequently, HER2 expression was detected in 43% of meningiomas. No significant
      difference was seen between grade I and grade II/III meningiomas, primary and
      recurrent tumors, and males and females from the point of view of HER2
      expression.

PMID- 22420925
TI  - An alternative to generating alternative interpretations in social cognitive
      therapy for psychosis.
AB  - BACKGROUND: Generating alternative interpretations is a widely used technique in
      cognitively-oriented treatments for psychosis, including social cognitive
      treatments. However, research on judgment and decision-making suggests that this
      technique may backfire among individuals with cognitive deficits. AIMS:
      Mary/Eddie/Bill (MEB) was developed as an alternative approach to help improve
      Theory of Mind, attributional bias and Jumping to Conclusions in psychosis. An
      initial pilot trial was conducted to evaluate the tolerability and potential
      efficacy of MEB. METHOD: Twenty-four outpatients with psychotic disorders
      participated in an uncontrolled trial. Social cognition, social functioning, and
      participant feedback were assessed. RESULTS: Treatment completers exhibited
      statistically significant improvements in Theory of Mind, social cognitive
      overconfidence and self-reported social engagement, and reported positive
      experiences with MEB. No improvements were observed in attributional bias.
      CONCLUSIONS: Given that there are risks associated with the use of traditional
      generating-alternatives techniques, the current findings support ongoing
      development of MEB and similar approaches.

PMID- 22420926
TI  - 3rd Georgian Bay International Conference on Bioinorganic Chemistry.

PMID- 22420927
TI  - Biomolecule binding vs. anticancer activity: reactions of Ru(arene)[(thio)pyr
      (id)one] compounds with amino acids and proteins.
AB  - The interactions of the ruthenium(arene) complexes [chlorido(eta(6)-p-cymene)(2
      methyl-3-(oxo-kappaO)-4H-pyran-4-onato-kappaO)ruthenium(II)] 1, [chlorido(eta(6)
      p-cymene)(2-methyl-3-(oxo-kappaO)-4H-thiopyran-4-onato-kappaS)ruthenium(II)] 2
      and [chlorido(eta(6)-p-cymene){N-[(ethoxycarbonyl)methyl]-3-(oxo-kappaO)-1H-pyrid
      2-onato-kappaO}ruthenium(II)] 3 with biomolecules such as l-methionine (Met) and
      ubiquitin (Ub) were investigated by electrospray ionization (ESI) ion trap mass
      spectrometry (MS). These Ru(II) compounds were shown to exhibit anticancer
      activity which varies depending on the (thio)pyr(id)onato ligands. Compounds 1
      and 3 reacted readily with the model protein Ub to yield stable [Ub+Ru(p-cym)]
      adducts (p-cym=eta(6)-p-cymene), whereas 2 was converted only to a minor degree.
      The protein adduct formation is reversible by incubation with N- and S-donor
      systems, the latter being more efficient. From these studies, an inverse
      correlation between metallodrug-protein interaction and cytotoxicity against
      human tumor cell lines was derived, where low protein binding ability is
      indicative of increased cytotoxic activity.

PMID- 22420928
TI  - Photocatalytic hydrogen evolution by a diiron hydrogenase model based on a
      peptide fragment of cytochrome c556 with an attached diiron carbonyl cluster and
      an attached ruthenium photosensitizer.
AB  - It is of particular interest to mimic the process of intramolecular electron
      relay at the active site of [FeFe]-hydrogenase in order to understand the
      mechanism of the catalytic activity of H(2) evolution. We have recently focused
      on using the native CXXCH peptide sequence of the C-terminal segment of
      cytochrome c(556) as a platform which holds a diiron carbonyl cluster via two
      cysteines and have attached a ruthenium photosensitizer via a histidine. The
      modified peptide with the two metal moieties is found to act as the photocatalyst
      for H(2) evolution with a turnover number of ~9 over 2h at pH 8.5 in the presence
      of ascorbate as a sacrificial reagent.

PMID- 22420929
TI  - Evaluating consistency in repeat surveys of injection drug users recruited by
      respondent-driven sampling in the Seattle area: results from the NHBS-IDU1 and
      NHBS-IDU2 surveys.
AB  - PURPOSE: We compared data from two respondent-driven sampling (RDS) surveys of
      Seattle-area injection drug users (IDU) to evaluate consistency in repeat RDS
      surveys. METHODS: The RDS-adjusted estimates for 16 key sociodemographic, drug
      related, sexual behavior, and HIV- and hepatitis C virus-related variables were
      compared in the 2005 and the 2009 National HIV Behavioral Surveillance system
      surveys (NHBS-IDU1 and NHBS-IDU2). Time trends that might influence the
      comparisons were assessed by the use of data from reported HIV cases in IDU,
      surveys of needle exchange users, and two previous IDU studies. RESULTS: NHBS
      IDU2 participants were more likely than NHBS-IDU1 participants to report older
      age, heroin as their primary injection drug, male-to-male sex, unprotected sex
      with a partner of nonconcordant HIV status, and to self-report HIV-positive
      status. NHBS-IDU2 participants were less likely to report residence in downtown
      Seattle, amphetamine injection, and a recent HIV test. Time trends among Seattle
      area IDU in age, male-to-male sex, and HIV testing could have influenced these
      differences. CONCLUSIONS: The number and magnitude of the estimated differences
      between the two RDS surveys appeared to describe materially different
      populations. This could be a result of changes in the characteristics of Seattle
      area IDU over time, of accessing differing subpopulations of Seattle IDU, or of
      high variability in RDS measurements.

PMID- 22420930
TI  - Measuring dynamic stability requirements during sitting pivot transfers using
      stabilizing and destabilizing forces in individuals with complete motor
      paraplegia.
AB  - Dynamic stability requirements have never been quantified when long-term manual
      wheelchair users transfer themselves in a seated position from an initial surface
      to a target surface, a functional task commonly referred to as sitting pivot
      transfers (SPTs). Ten individuals with spinal cord injury (SCI), who rely on a
      manual wheelchair for mobility, underwent a comprehensive biomechanical SPT
      assessment. SPTs performed toward a target seat of same height (even) and a seat
      10cm higher than the initial seat (uneven), repeated three times for each task,
      were assessed. A dynamic equilibrium model, continuously measuring the
      theoretical forces required to move the center of pressure to the limit of the
      base of support (destabilizing force) and to neutralize the kinetic energy and
      stop the displacement of the center of mass at the limit of the base of support
      (stabilizing force) at each instance during the performance of SPTs, was used to
      identify the phases of greatest instability during the SPT tasks. The greatest
      levels of instability were reached around the time the buttocks lost contact with
      the initial seat and around the time the buttocks landed on the target seat (pre-
      and post-lift transition phases). These transition periods, characterized by the
      lowest destabilizing force (424.7-487.1N) and the greatest stabilizing force
      (24.2-33.2N), confirmed the greatest level of instability. The height of the
      target seat had no significant effect (p=0.278-0.739) on dynamic postural
      stability requirements during the SPTs. During SPTs towards even and uneven
      target seats, the greatest postural instability occurs during the transition
      phases in individuals with complete motor thoracic SCI.

PMID- 22420931
TI  - A Java simulator of Rescorla and Wagner's prediction error model and configural
      cue extensions.
AB  - In this paper we present the "R&W Simulator" (version 3.0), a Java simulator of
      Rescorla and Wagner's prediction error model of learning. It is able to run whole
      experimental designs, and compute and display the associative values of elemental
      and compound stimuli simultaneously, as well as use extra configural cues in
      generating compound values; it also permits change of the US parameters across
      phases. The simulator produces both numerical and graphical outputs, and includes
      a functionality to export the results to a data processor spreadsheet. It is user
      friendly, and built with a graphical interface designed to allow neuroscience
      researchers to input the data in their own "language". It is a cross-platform
      simulator, so it does not require any special equipment, operative system or
      support program, and does not need installation. The "R&W Simulator" (version
      3.0) is available free.

PMID- 22420932
TI  - Appetitive aggression in former combatants--derived from the ongoing conflict in
      DR Congo.
AB  - Soldiers and combatants often report that committing violence can be appealing,
      fascinating and exciting (Elbert, Weierstall, & Schauer, 2010). This appetite for
      aggression was investigated in a sample of 224 former combatants from different
      armed groups and forces in eastern DRC. In a semistructured interview they were
      questioned about their military history, exposure to violence and perpetrated
      violence. Appetitive aggression was assessed with a 15-item-scale (Weierstall &
      Elbert, 2011), which was successfully implemented in comparable samples
      (Weierstall, Schalinski, Crombach, Hecker, & Elbert, submitted for publication).
      A sequential multiple regression was conducted to determine possible predictors
      of appetitive aggression. Perpetrated violence types, recruitment type, and
      joining as a child were significant predictors and explained 26% of the
      variability in appetitive aggression. Duration or military rank within the armed
      group and exposure to violence did not play a significant role. Thus, combatants
      reporting high levels of appetitive aggression are characterized by perpetrating
      a high number of violent acts, joining armed groups on their own accord and as
      children. Joining an armed group on one's own accord indicates pre-existing
      appetitive aggression. However, joining young and perpetrating violence on a
      regular basis seem to intensify the appetite for aggression.

PMID- 22420933
TI  - Androgen deprivation therapy of self-identifying, help-seeking pedophiles in the
      Dunkelfeld.
AB  - Androgen deprivation therapy (ADT) is considered an effective strategy in sexual
      offender treatment. However, the evidence base concerning its effects on sexual
      arousal control is limited. Past research has focused almost exclusively on men
      in forensic contexts. The present retrospective observational study provided data
      on ADT in a sample of self-identifying, help-seeking pedohebephilic men applying
      for a one-year group therapy program. Factors possibly influencing the readiness
      to take up or discontinue ADT were presented. Effects of a combination of ADT and
      group psychotherapy program on changes in paraphilic sexual behavior and
      associated psychological factors were examined. The proportion of men having
      taken up ADT was rather small (n=15). Greater awareness of potentially risky
      situations to commit child sexual offenses and self-rated uncontrollability of
      sexual urges were identified as characterizing men resorting to ADT.
      Additionally, these men were initially more open to include medical treatment.
      Examination of the effects of ADT and psychotherapy was limited to a sample of
      six men providing complete data sets. Descriptive data demonstrated a reduction
      of paraphilic sexual behaviors, an increase of risk-awareness and self-efficacy,
      and a decrease of offense-supportive cognitions and self-esteem. The present
      study underlined the importance of careful education and monitoring of self
      identifying, help-seeking pedohebephilic patients interested in ADT concerning
      the effects and side effects of the treatment in a clinical context.

PMID- 22420934
TI  - Undetected and detected child sexual abuse and child pornography offenders.
AB  - Current knowledge about risk factors for child sexual abuse and child pornography
      offenses is based on samples of convicted offenders, i.e., detected offenders.
      Only few studies focus on offenders not detected by the criminal justice system.
      In this study, a sample of 345 self-referred pedophiles and hebephiles was
      recruited from the community. All participants met DSM-IV-TR criteria for
      pedophilia or hebephilia (paraphilia not otherwise specified), were assured of
      confidentiality, and self-reported lifetime sexual offending against prepubescent
      and/or pubescent children. Two sets of group comparisons were conducted on self
      report data of risk factors for sexual reoffending. Measures of risk factors
      address the following dimensions identified in samples of convicted offenders:
      sexual preferences (i.e. co-occurring paraphilias), sexual self-regulation
      problems, offense-supportive cognitions, diverse socio-affective deficits, and
      indicators of social functioning (e.g., education, employment). Men who admitted
      current or previous investigation or conviction by legal authorities (detected
      offenders) were compared with those who denied any detection for their sexual
      offenses against children (undetected offenders). Group comparisons (detected vs.
      undetected) were further conducted for each offense type separately (child
      pornography only offenders, child sexual abuse only offenders, mixed offenders).
      Although there were more similarities between undetected and detected offenders,
      selected measures of sexual-self regulation problems, socio-affective deficits,
      and social functioning data demonstrated group differences.

PMID- 22420935
TI  - The modification of criminogenic factors on addicted offenders. The effectiveness
      of the Reasoning and Rehabilitation Program.
AB  - At the Clinic of Forensic Psychiatry in Rostock, Germany, we treat addicted
      offenders in a closed psychiatric setting. In 2009 we implemented the "Reasoning
      and Rehabilitation Program" (R & R, Ross & Fabiano, 1986), a cognitive skills
      program, in our clinic. There are several international studies confirming the
      efficacy of this training in diminishing recidivism. We examined a sample of 31
      inpatients randomly distributed among the experimental (R & R) and the control
      group. Most of the study participants had committed homicide or other serious
      violent offenses. Prisoners with schizophrenia, organic mental disorders and
      mental retardation were excluded from the study. The target skills were assessed
      by treating psychotherapists, primary nurses and by the patients themselves. Our
      findings indicated that problem-solving, awareness of consequences, social
      perspective-taking, cognitive style, the ability to learn by experience, and
      persistence in the experimental group were significantly improved. The awareness
      of consequences has changed significantly in the assessment of the treating
      psychotherapists, the primary nurses, and the offenders themselves. Our current
      data are similar to our recent work, where we found significant changes in mental
      flexibility, planning, and problem-solving and positively assessed tendencies in
      some skills (Wettermann et al., 2012, 2011). Verification of these findings in a
      larger sample would strengthen the research foundation for this important
      training to diminish prisoner recidivism.

PMID- 22420936
TI  - Use of modafinil in patients with epilepsy.
AB  - Fatigue and excessive daytime sleepiness are common symptoms in patients with
      neurological injury. Modafinil has been shown to ameliorate these symptoms, but
      its use in patients with seizures has been limited because of safety concerns.
      Using a large centralized clinical registry, we performed a retrospective chart
      review of patients with a diagnosis of epilepsy who were given modafinil over a
      10-year period. A total of 205 patients were analyzed. There were 91 patients who
      had seizures while taking modafinil; there was no relationship between modafinil
      dosage and whether the patient had seizures. There were 6 patients in whom
      modafinil was discontinued because of concern for seizure exacerbation, and 4
      patients had de novo seizures after starting modafinil. In 29 patients with
      epilepsy only, no major seizure exacerbation was seen. Modafinil is potentially
      safe in patients with epilepsy, but further prospective studies are needed to
      fully determine its safety and efficacy.

PMID- 22420937
TI  - Lysosomal enzyme can bypass the blood-brain barrier and reach the CNS following
      intranasal administration.
AB  - Here we provide the first evidence that therapeutic levels of a lysosomal enzyme
      can bypass the blood-brain barrier following intranasal administration. alpha-L
      iduronidase (IDUA) activity was detected throughout the brains of IDUA-deficient
      mice following a single intranasal treatment with concentrated Aldurazyme(r)
      (laronidase) and was also detected after intranasal treatment with an adeno
      associated virus (AAV) vector expressing human IDUA. These results suggest that
      intranasal routes of delivery may be efficacious in the treatment of lysosomal
      storage disorders.

PMID- 22420938
TI  - Evaluation of programmatic changes to an antimicrobial stewardship program with
      house officer feedback.
AB  - RATIONALE, AIMS AND OBJECTIVES: A collegial relationship between prescribers and
      antimicrobial stewards, along with an appreciation of the importance of
      antimicrobial stewardship, is essential for optimal functioning of an
      antimicrobial stewardship program (ASP). Programmatic adjustments based on
      feedback may be beneficial to the success of ASPs. The objective of this study is
      to assess the experience of house officers with the ASP and the effect of
      programmatic improvements. METHODS: A survey of house officers at an academic
      medical centre was conducted assessing their experience with the ASP before
      (2008) and after (2010) programmatic interventions were instituted. RESULTS: Of
      225 house officer surveys sent, we received 97 responses (88% from medical
      doctors). The majority indicated that ASP was either very or somewhat important
      in fighting antibiotic resistance (100%), improving patient care (97%),
      preventing medication errors (91%) and containing health care costs (89%). Ninety
      one per cent indicated either a very good or good educational experience with the
      ASP. The ASP often reminded respondents of a patient's allergy (31%), to adjust
      for renal function (78%), and 38% were prevented from making a medication error.
      Comparing 2008 and 2010, a higher proportion of respondents in 2010 said they had
      a very good or good educational experience with ASP [84% versus 98%, odds ratio
      (OR) = 8.40, P = 0.022] and a lower proportion of respondents reported confusion
      about ASP procedures (59% versus 39%, OR = 0.43, P = 0.048). CONCLUSIONS: House
      officer feedback resulted in ASP policy changes which improved the ASP
      experience.

PMID- 22420939
TI  - Serum beta-carotene in relation to risk of prostate cancer: the Kuopio Ischaemic
      Heart Disease Risk Factor study.
AB  - Results from epidemiologic studies on the association between circulating
      carotenoid concentrations and the risk of prostate cancer are still inconsistent.
      We studied whether serum concentrations of carotenoids were associated with the
      risk of developing prostate cancer. The study population consisted of 997 middle
      aged Finnish men (56.1 +/- 6.6 yr) in the Kuopio Ischaemic Heart Disease Risk
      Factor (KIHD) cohort. Serum concentrations of carotenoids were measured by high
      performance liquid chromatography. Subjects were classified into tertiles
      according to their serum concentrations of antioxidants. Relative risks (RRs)
      were estimated by using the Cox proportional hazard models. During the mean
      follow-up time of 15 yr, a total of 68 prostate cancer cases occurred. After
      adjusting for age, examination yr, family history of cancer, BMI, pack-yr of
      smoking, alcohol consumption, education, physical activity, serum total
      cholesterol, and serum alpha-linolenic acid, men in the highest tertile of serum
      concentrations of beta-carotene had 2.3-fold higher risk of prostate cancer as
      compared to those in the lowest tertile (RR = 2.29, 95% CI: 1.12-4.66; P =
      0.023). alpha-Tocopherol and retinol were not associated with prostate cancer.
      This prospective study suggests that high-serum beta-carotene concentrations may
      increase the risk of prostate cancer in middle-aged men.

PMID- 22420942
TI  - Rescue of the transcription factors Sp1 and NFI in human skin keratinocytes
      through a feeder-layer-dependent suppression of the proteasome activity.
AB  - Co-culturing human skin keratinocytes along with a feeder layer has proven to
      considerably improve their proliferative properties by delaying massive induction
      of terminal differentiation. Through a yet unclear mechanism, we recently
      reported that irradiated 3T3 (i3T3) fibroblasts used as a feeder layer increase
      the nuclear content of Sp1, a positive transcription factor (TF) that plays a
      critical role in many cellular functions including cell proliferation, into both
      adult skin keratinocytes and newborn skin keratinocytes. In this study, we
      examined the influence of i3T3 on the expression and DNA binding of NFI, another
      TF important for cell proliferation and cell cycle progression, and attempted to
      decipher the mechanism by which the feeder layer contributes at maintaining
      higher levels of these TFs in skin keratinocytes. Our results indicate that co
      culturing both adult skin keratinocytes and newborn skin keratinocytes along with
      a feeder layer dramatically increases glycosylation of NFI and may prevent it
      from being degraded by the proteasome.

PMID- 22420940
TI  - Peripheral FAAH inhibition causes profound antinociception and protects against
      indomethacin-induced gastric lesions.
AB  - Fatty-acid amide hydrolase (FAAH) catalyzes the intracellular hydrolysis of the
      endocannabinoid anandamide and other bioactive lipid amides. In the present
      study, we conducted a comparative characterization of the effects of the newly
      identified brain-impermeant FAAH inhibitor, URB937 ([3-(3-carbamoylphenyl)-4
      hydroxy-phenyl] N-cyclohexylcarbamate), in various rodent models of acute and
      persistent pain. When administered by the oral route in mice, URB937 was highly
      active (median effective dose, ED(50), to inhibit liver FAAH activity: 0.3mgkg(
      1)) and had a bioavailability of 5.3%. The antinociceptive effects of oral URB937
      were investigated in mouse models of acute inflammation (carrageenan), peripheral
      nerve injury (chronic sciatic nerve ligation) and arthritis (complete Freund's
      adjuvant). In all models, URB937 was as effective or more effective than standard
      analgesic and anti-inflammatory drugs (indomethacin, gabapentin, dexamethasone)
      and reversed pain-related responses (mechanical hyperalgesia, thermal
      hyperalgesia, and mechanical allodynia) in a dose-dependent manner. ED(50) values
      ranged from 0.2 to 10mgkg(-1), depending on model and readout. Importantly,
      URB937 was significantly more effective than two global FAAH inhibitors, URB597
      and PF-04457845, in the complete Freund's adjuvant model. The effects of a
      combination of URB937 with the non-steroidal anti-inflammatory agent,
      indomethacin, were examined in the carrageenan and chronic sciatic nerve ligation
      models. Isobolographic analyses showed that the two compounds interacted
      synergistically to attenuate pain-related behaviors. Furthermore, URB937 reduced
      the number and severity of gastric lesions produced by indomethacin, while
      exerting no ulcerogenic effect when administered alone. The results indicate that
      the peripheral FAAH inhibitor URB937 is more effective than globally active FAAH
      inhibitors at inhibiting inflammatory pain. Our findings further suggest that
      FAAH and cyclooxygenase inhibitors interact functionally in peripheral tissues,
      to either enhance or hinder each other's actions.

PMID- 22420941
TI  - Viruses exacerbating chronic pulmonary disease: the role of immune modulation.
AB  - Chronic pulmonary diseases are a major cause of morbidity and mortality and their
      impact is expected to increase in the future. Respiratory viruses are the most
      common cause of acute respiratory infections and it is increasingly recognized
      that respiratory viruses are a major cause of acute exacerbations of chronic
      pulmonary diseases such as asthma, chronic obstructive pulmonary disease and
      cystic fibrosis. There is now increasing evidence that the host response to virus
      infection is dysregulated in these diseases and a better understanding of the
      mechanisms of abnormal immune responses has the potential to lead to the
      development of new therapies for virus-induced exacerbations. The aim of this
      article is to review the current knowledge regarding the role of viruses and
      immune modulation in chronic pulmonary diseases and discuss avenues for future
      research and therapeutic implications.

PMID- 22420944
TI  - Effects of transcranial Direct Current Stimulation (tDCS) on cortical activity: a
      computational modeling study.
AB  - Although it is well-admitted that transcranial Direct Current Stimulation (tDCS)
      allows for interacting with brain endogenous rhythms, the exact mechanisms by
      which externally-applied fields modulate the activity of neurons remain elusive.
      In this study a novel computational model (a neural mass model including
      subpopulations of pyramidal cells and inhibitory interneurons mediating synaptic
      currents with either slow or fast kinetics) of the cerebral cortex was elaborated
      to investigate the local effects of tDCS on neuronal populations based on an in
      vivo experimental study. Model parameters were adjusted to reproduce evoked
      potentials (EPs) recorded from the somatosensory cortex of the rabbit in response
      to air-puffs applied on the whiskers. EPs were simulated under control condition
      (no tDCS) as well as under anodal and cathodal tDCS fields. Results first
      revealed that a feed-forward inhibition mechanism must be included in the model
      for accurate simulation of actual EPs (peaks and latencies). Interestingly,
      results revealed that externally-applied fields are also likely to affect
      interneurons. Indeed, when interneurons get polarized then the characteristics of
      simulated EPs become closer to those of real EPs. In particular, under anodal
      tDCS condition, more realistic EPs could be obtained when pyramidal cells were
      depolarized and, simultaneously, slow (resp. fast) interneurons became de- (resp.
      hyper-) polarized. Geometrical characteristics of interneurons might provide some
      explanations for this effect.

PMID- 22420943
TI  - Effects of the combination of RAD001 and docetaxel on breast cancer stem cells.
AB  - Recent evidence has suggested that breast cancer contains a rare population of
      cells called cancer stem cells (CSCs), which have an extensive self-renewal
      ability and contribute to metastasis and therapeutic resistance. This study
      evaluated the in vitro and in vivo effects of RAD001 (Everolimus) alone or in
      combination with docetaxel on stem cells from primary breast cancer cells and two
      breast cancer cell lines (MCF-7 and MDA-MB-231). In In vitro studies, we sorted
      ESA(+)CD44(+)CD24(-/low) cells as stem cells using flow cytometry from primary
      breast cancer cells, MCF-7 and MDA-MB-231 cell lines. MTT assays were used to
      quantify the inhibitory effect of the drugs on total cells and stem cells.
      Apoptosis and the cell cycle distributions of stem cells were examined by flow
      cytometry. The tumourigenicity of stem cells after treatment was investigated by
      soft agar colony formation assays. In In vivo studies, the BALB/c mice were
      injected with MDA-MB-231 stem cells and the different treatments were
      administered. After necropsy, the expression of Ki67, CD31, AKT1, and phospho-AKT
      (Thr308) was analysed by immunohistochemistry. In In vitro studies, all three
      populations of stem cells were resistant to the standard treatment doses of
      docetaxel compared with total cells treated with the same drug. Treatment with
      RAD001 resulted in growth inhibition of all stem cells in a dose-dependent
      manner. An additive growth inhibitory effect of the combination treatment on the
      three stem cells was observed in in vitro compared with treatment with RAD001
      alone (P<0.001). In addition, an increase in G2/M cell cycle arrest and an
      increased population of cells in early apoptosis were seen in the combination
      treatment group compared with either single-agent group (P<0.01). In vivo, the
      volumes of the xenograft tumours significantly decreased in RAD001 alone group
      compared to control group (P=0.008), and RAD001 plus docetaxel therapy was much
      more effective at reducing tumour volume in mice compared with either single
      agent alone (P<0.05). Compared with RAD001 alone, the combination of RAD001 and
      docetaxel reduced the expression of Ki67, CD31, AKT1 and phospho-AKT (Thr308)
      (P<0.05). We conclude that the combination treatment of RAD001 and docetaxel can
      inhibit the growth of stem cells in vitro and in vivo by inhibiting cell
      proliferation, inducing apoptosis, cell cycle arrest and reducing the expression
      of Ki67, CD31, AKT1 and phospho-AKT (Thr308). These data indicate that
      combination treatment with RAD001 and docetaxel may represent an effective
      therapy for breast cancer. However, further studies are required to evaluate the
      drug interaction between RAD001 and docetaxel in the clinical setting.

PMID- 22420945
TI  - Do calcium fluxes within cortical bone affect osteocyte mechanosensitivity?
AB  - Bone reacts to local mechanical environment by adapting its structure. Bone is
      also a key source of calcium for the body homeostasis. Osteocytes, cells located
      within the bone tissue, are thought to play a major role in sensing mechanical
      signals and regulating bone remodeling. Interestingly, osteocytes were also shown
      to directly participate in the calcium homeostasis by regulating dissolution and
      deposition of calcium in the perilacuno-pericanalicular space. However, it is not
      known if osteocyte's roles in mechanoregulation and calcium homeostasis have any
      significant crosstalk. Previously, a multi-scale mathematical model of the
      interstitial fluid flow through the canaliculus was developed, which took into
      account physicochemical phenomena including hydraulic effects, formation of
      electrical double layer, osmosis and electro-osmosis. We extended this model to
      include the directional movement of calcium from and into the bone tissue, and
      assessed the shear stress at the osteocyte membrane. We have found that in the
      bulk of the canalicular space the fluid flow due to chemical gradient generated
      by deposition or dissolution of calcium is negligible compared to the fluid flow
      due to hydraulic pressure. However, at the osteocyte proximity, the presence of
      calcium gradient generated sufficient fluid flow to induce significant changes in
      the shear stress on the osteocyte membrane. Calcium deposition and dissolution on
      the canalicular wall resulted in increased or decreased shear stress on the
      osteocyte membrane respectively. Thus, our data demonstrate that strong calcium
      fluxes due to whole body calcium homeostasis may affect mechanical forces
      experienced by osteocytes.

PMID- 22420946
TI  - Characteristic time in quasispecies evolution.
AB  - The time a phenotype takes to achieve a stationary state from an initial
      condition depends on multiple factors. In particular, it is a function of both
      its fitness and its mutation rate. We evaluate the average time, referred to as
      the characteristic time, T(c), that the system takes to reach a final steady
      state of simple models of populations formed by self-replicative sequences. The
      dependence of T(c) on the mutation rate and on the fitness landscape is also
      studied. For simple fitness landscapes, e.g. single peak, the characteristic time
      can be analytically obtained as a function of the system parameters. In this
      case, T(c) for obtaining the quasispecies distribution presents a maximum at a Q
      value that depends on the initial conditions and decreases monotonously as the
      mutation rate tends to zero. For most of the complex landscapes handled in this
      paper, the characteristic time to achieve the quasispecies distribution picked
      around the fittest phenotype attains a local minimum for a given mutation rate
      between 0 and the Q-value at which T(c) reaches its local maximum. Thus, in these
      cases, an optimum value for the mutation rate exists that corresponds to the
      lowest value of the characteristic time for quasispecies evolution.

PMID- 22420947
TI  - A mathematical analysis of public avoidance behavior during epidemics using game
      theory.
AB  - The decision of individuals to engage in public avoidance during epidemics is
      modeled and studied using game theory. The analysis reveals that the set of Nash
      equilibria of the model, as well as how the equilibria compare to the social
      optimum, depend on the contact function that governs the rate at which encounters
      occur in public. If the contact ratio - defined to be the ratio of the contact
      rate to the number of people out in public - is increasing with the number of
      people out in public, then there exists a unique Nash equilibrium. Moreover, in
      equilibrium, the amount of public avoidance is too low with respect to social
      welfare. On the other hand, if the contact ratio is decreasing in the number of
      people out in public, then there can be multiple Nash equilibria, none of which
      is in general socially optimal. Furthermore, the amount of public avoidance in
      equilibrium with a decreasing contact ratio is too high in that social welfare
      can be increased if more susceptible individuals choose to go out in public. In
      the special case where the contact ratio does not vary with the number of people
      out in public, there is a unique Nash equilibrium, and it is also the socially
      optimal outcome.

PMID- 22420948
TI  - Health related quality of life and impact of infectious comorbidity in outpatient
      management of patients with acute leukemia.
AB  - Although survival has improved among patients with acute leukemia, there is still
      a considerable risk of severe complications throughout the course of treatment.
      This contrast increases the interest in monitoring health related quality of life
      (HRQOL) in these patients. This study presents a longitudinal HRQOL evaluation
      (European Organisation for Research and Treatment of Cancer core 30-item
      questionnaire; EORTC-QLQ C-30) and the impact of infectious comorbidity among 60
      patients with leukemia (median age 47) treated in an outpatient management
      program at Copenhagen University Hospital. Significant improvement was seen on
      several HRQOL scores during follow-up. Explorative general linear models (GLMs)
      suggest that high cumulative severity of infectious comorbidity significantly
      reduces physical functioning and overall quality of life at treatment completion.

PMID- 22420949
TI  - Hypereosinophilia driven by GM-CSF in large-cell carcinoma of the lung.
AB  - In contrast to leukocytosis, paraneoplastic hypereosinophilia is uncommon in lung
      cancer. We present a patient with large-cell carcinoma of the lung, in which
      cancer cells generate large amounts of GM-CSF leading to a leukemoid reaction
      with prominent hypereosinophilia and potentially involved in autocrine tumor
      stimulation.

PMID- 22420950
TI  - Retrospective study of erlotinib in patients with advanced squamous lung cancer.
AB  - BACKGROUND: The effective targeted therapy for lung squamous cell carcinoma (SCC)
      is needed. The epidermal growth factor receptor (EGFR) mutation rate is low in
      lung SCC. The aim of this study was to evaluate the status of erlotinib treatment
      and EGFR mutation in lung SCC patients. METHODS: We retrospectively enrolled lung
      cancer patients with SCC histology and history of erlotinib treatment. The
      primary objective was to assess overall response rate (ORR) and disease control
      rate (DCR) and the secondary objective was to assess progression-free survival
      (PFS) and overall survival (OS). EGFR mutations were assessed in parts of
      patients using both direct sequencing and protein nucleic acid-locked nucleic
      acid polymerase chain reaction (PNA-LNA PCR) clamp methods. RESULTS: In total, 92
      patients were analyzed (75 men and 17 women, median age 69 years, and 74 current
      or former smokers). Sixteen patients achieved partial response and 9 had stable
      disease. The ORR was 17.4% and the DCR was 27.2%. The PFS and OS were longer in
      patients with disease control than with progressive disease (PFS 7.8 versus 1.3
      months and OS 20.7 versus 2.7 months, both p<0.0001). The 1-year survival rate
      was 21.7%. In 27 patients with adequate specimens for molecular analysis
      (including 4 PR and 4 SD), two (7.4%) had EGFR complex mutations. One patient
      experienced response to erlotinib and the other did not. CONCLUSIONS: A
      significant proportion of lung SCC patients would derive a clinical benefit from
      erlotinib treatment. The relatively higher response rate than the EGFR mutation
      rate in present study needs further evaluation.

PMID- 22420951
TI  - shRNA-mediated knockdown of Bmi-1 inhibit lung adenocarcinoma cell migration and
      metastasis.
AB  - Bmi-1 has been implicated in cancer cell growth and metastasis in a variety of
      tumor types. In this study, we sought to evaluate the expression of Bmi-1 in lung
      adenocarcinoma samples, and to determine if a correlation exists between Bmi-1
      expression and clinical features of lung cancer, such as metastasis. Our results
      showed that Bmi-1 expression is increased in lung cancer tissues compared to
      adjacent non-cancerous tissues, and is associated with clinical features of lung
      cancer, including clinical stage and distant metastasis. We were then interested
      in determining if shRNA-mediated knockdown of Bmi-1 would inhibit metastasis of
      lung adenocarcinoma cells. To this end, we chose the most efficient shRNA
      duplexes targeting Bmi-1, and constructed two stably transfected lung
      adenocarcinoma cell lines (A549 and SPCA1). The shRNA-mediated knockdown of Bmi-1
      significantly reduced migration in vitro, and metastasis in vivo, of A549 and
      SPCA1 cells. More importantly, knockdown of Bmi-1 also upregulated PTEN
      expression, and downregulated p-Akt and VEGF expression. These data support the
      hypothesis that Bmi-1 regulates key pathways involved in the metastasis of lung
      adenocarcinoma cells.

PMID- 22420952
TI  - Quantifying judicious use of health information technology.
AB  - RATIONALE, AIMS AND OBJECTIVES: Sufficient evidence suggests that health
      information technology (HIT) will soon become part of physician procedure. This
      paper poses that the outcome of using HIT is affected by the intentions of use.
      Note that ethical indoctrination is a crucial mechanism for monitoring
      physicians. Judicious and sufficient use of HIT is expected to be the
      prerequisite for deploying these technologies to help in delivering better care.
      This research paper, therefore, aims to define professional concerns and intent
      to use HIT, and identify their associations. METHODS: A survey study was
      conducted to collect data for developing a seven-dimensional eHealth success
      measure. This paper focuses on deriving a structural equation model that can
      explain the associations among professional concerns and intent to use HIT.
      Statistical analyses were, therefore, only performed on the Intent to Use and
      Physician Attributes constructs. RESULTS: The statistical results show that
      altruism, autonomy, physician-patient relationship and (subconscious) autonomy
      significantly associate with each other at least at P < 0.05. Only altruism shows
      to be a significant determinant of intent to use HIT (with P = 0.00005). Other
      professional concerns only associate with it indirectly through altruism.
      CONCLUSIONS: Medicine has been a science-using and compassionate practice.
      Medical practice including HIT use may only be reliably assessed from a
      sociotechnical perspective. Professional concerns show to be associated with
      intent to use HIT is an expected result. This research direction may contribute
      to deriving policies to deploy HIT for delivering better care through
      implementing sufficient and judicious HIT use.

PMID- 22420953
TI  - Effect of medetomidine-butorphanol and dexmedetomidine-butorphanol combinations
      on intraocular pressure in healthy dogs.
AB  - OBJECTIVE: To assess the effects of intravenous (IV) medetomidine-butorphanol and
      IV dexmedetomidine-butorphanol on intraocular pressure (IOP). STUDY DESIGN:
      Prospective, randomized, blinded clinical study. ANIMALS: Forty healthy dogs.
      Mean +/- SD body mass 37.6 +/- 6.6 kg and age 1.9 +/- 1.3 years. METHODS: Dogs
      were allocated randomly to receive an IV combination of dexmedetomidine, 0.3 mg
      m(-2), combined with butorphanol, 6 mg m(-2), (group DEX) or medetomidine 0.3 mg
      m(-2), combined with butorphanol 6 mg m(-2), (group MED). IOP and pulse (PR) and
      respiratory (f(R) ) rates were measured prior to (baseline) and at 10 (T10), 20
      (T20), 30 (T30) and 40 (T40) minutes after drug administration. Oxygen saturation
      of hemoglobin (SpO(2)) was monitored following sedation. Data were analyzed by
      anova followed by Dunnett's tests for multiple comparisons. Changes were
      considered significant when p < 0.05. RESULTS: Following drug administration, PR
      and f(R) were decreased significantly at all time points but did not differ
      significantly between groups. Baseline IOP in mmHg was 14 +/- 2 for DEX and 13 +/
      2 for MED. With both treatments, at T10, IOP increased significantly (p <
      0.001), reaching 20 +/- 3 and 17 +/- 2 for DEX and MED respectively. This value
      for DEX was significantly higher than for MED. There were no significant
      differences in IOP values between groups at any other time points. At T30 and
      T40, IOP in both groups was below baseline (DEX, 12 +/- 2 and 11 +/- 2: MED 12 +/
      2 and 11 +/- 2) and this was statistically significant, for DEX. CONCLUSIONS AND
      CLINICAL RELEVANCE: At the documented doses, both sedative combinations induced a
      transient increase and subsequent decrease of IOP relative to baseline, which
      must be taken into consideration when planning sedation of animals in which
      marked changes in IOP would be undesirable.

PMID- 22420954
TI  - Liquid chromatography-flame ionisation detection using a nebuliser/spray chamber
      interface. Part 2. Comparison of functional group responses.
AB  - The application of a LC-nebuliser/spray chamber interface-flame ionisation
      detection has been demonstrated for the superheated water liquid chromatography
      of a wide range of aliphatic and aromatic analytes. The linearity and sensitivity
      of the response of volatile and involatile analytes have been compared. The
      response of the detector toward different analytes is similar to that in GC-FID
      and for volatile analytes was comparable to UV detection. However, the responses
      from involatile analytes, such as amino acids and carbohydrates, were poor and
      often lower than for a refractive index detector.

PMID- 22420955
TI  - Taylor dispersion analysis with two detection points on a commercial capillary
      electrophoresis apparatus.
AB  - This work describes a simple technical modification for doing Taylor dispersion
      analysis with two UV detection points on a commercial capillary electrophoresis
      apparatus. So far, double UV detection was only possible using specific detectors
      that are external to the capillary electrophoresis apparatus. In this work, the
      detection interface of the capillary electrophoresis apparatus was easily
      modified to allow the introduction and the superposition of two capillary windows
      in the same interface (at the same detection point). This modification made
      possible the double detection of the sample zone in Taylor dispersion analysis
      using a loop. The peak dispersion using the modified interface was similar to
      that obtained on a non-modified UV interface. Diffusion coefficients (and the
      corresponding hydrodynamic radii) of small molecule and proteins were determined
      in good agreement with values of the literature and with RSD lower than 5%.

PMID- 22420956
TI  - A simple and rapid extraction method for sensitive determination of
      perfluoroalkyl substances in blood serum suitable for exposure evaluation.
AB  - In this work, we propose a microextraction method based on a new supramolecular
      solvent (SUPRAS) made up of reverse aggregates of hexanoic acid, combined with
      liquid chromatography/triple quadrupole mass spectrometry (LC/QQQ MS-MS) for the
      determination of the perfluoroalkyl substances (PFASs) in blood serum. A SUPRAS
      is a nano-structured liquid made up of surfactant aggregates synthesized through
      a self-assembly process. The method involved the acidification of 765 MUL of
      blood serum (600 MUmol of hydrochloric acid per mL of serum) followed by the
      addition of hexanoic acid (97 MUL) and tetrahydrofuran (THF) (600 MUL),
      conditions under which the supramolecular solvent (~360 MUL) formed in situ after
      vortex-shaking and centrifugation. Parameters affecting extraction efficiency and
      concentration factors were studied. The overall sample treatment took only 20 min
      and several samples (20-30) can be simultaneously analyzed using conventional lab
      equipments, making additional investments unnecessary. Recoveries for the
      internal standards in samples ranged from 75 to 89% with relative standard
      deviations between 1 and 15%. Calibration was based on the use of internal
      standards. The method was very sensitive with detection limits ranging from 2 to
      20 pg mL(-1) for PFASs. The approach developed was successfully applied to the
      determination of PFASs in different blood serum samples. The concentration of
      PFASs found in samples of animal origin ranged between 17 and 197.3 pg mL(-1) and
      between 84 and 5168 pg mL(-1) in samples of human origin. Both the analytical and
      operational features of this method make it suitable for the evaluation of
      exposure to PFASs.

PMID- 22420957
TI  - Twenty-two-year trends in incidence of myocardial infarction, coronary heart
      disease mortality, and case fatality in 4 US communities, 1987-2008.
AB  - BACKGROUND: Knowledge of trends in the incidence of and survival after myocardial
      infarction (MI) in a community setting is important to understanding trends in
      coronary heart disease (CHD) mortality rates. METHODS AND RESULTS: We estimated
      race- and gender-specific trends in the incidence of hospitalized MI, case
      fatality, and CHD mortality from community-wide surveillance and validation of
      hospital discharges and of in- and out-of-hospital deaths among 35- to 74-year
      old residents of 4 communities in the Atherosclerosis Risk in Communities (ARIC)
      Study. Biomarker adjustment accounted for change from reliance on cardiac enzymes
      to widespread use of troponin measurements over time. During 1987-2008, a total
      of 30 985 fatal or nonfatal hospitalized acute MI events occurred. Rates of CHD
      death among persons without a history of MI fell an average 4.7%/y among men and
      4.3%/y among women. Rates of both in- and out-of-hospital CHD death declined
      significantly throughout the period. Age- and biomarker-adjusted average annual
      rate of incident MI decreased 4.3% among white men, 3.8% among white women, 3.4%
      among black women, and 1.5% among black men. Declines in CHD mortality and MI
      incidence were greater in the second decade (1997-2008). Failure to account for
      biomarker shift would have masked declines in incidence, particularly among
      blacks. Age-adjusted 28-day case fatality after hospitalized MI declined 3.5%/y
      among white men, 3.6%/y among black men, 3.0%/y among white women, and 2.6%/y
      among black women. CONCLUSIONS: Although these findings from 4 communities may
      not be directly generalizable to blacks and whites in the entire United States,
      we observed significant declines in MI incidence, primarily as a result of
      downward trends in rates between 1997 and 2008.

PMID- 22420958
TI  - Changes in antibiotic resistance patterns of conjunctival flora due to repeated
      use of topical antibiotics after intravitreal injection.
AB  - OBJECTIVE: To determine the effect of repeated intermittent use of topical
      antibiotics after intravitreal injections on conjunctival bacterial flora and
      antibiotic resistance. DESIGN: Cross-sectional case-control study. PARTICIPANTS
      AND CONTROLS: A total of 80 eyes of 40 patients were enrolled (40 study eyes, 40
      control eyes). Patients were enrolled with unilateral exudative age-related
      macular degeneration who had received at least 3 prior intravitreal injections
      with use of postinjection topical antibiotics. Patients had received an average
      of 7 (range, 3-13) intravitreal injections before enrollment. METHODS: At the
      time of enrollment, the inferior fornix of the treated eye was swept with a
      culture swab before use of povidone iodine; the inferior fornix of the fellow eye
      was also cultured and served as a control. The culture and sensitivity data from
      the study and control eyes were analyzed. MAIN OUTCOME MEASURES: The rate of
      antibiotic resistance among the conjunctival bacterial flora of the study eyes
      and control eyes. RESULTS: A total of 80 eyes of 40 patients were enrolled in the
      study; 29 patients used trimethoprim/polymyxin B drops, and 11 patients used
      fluoroquinolone drops after each injection. A total of 58 bacterial colonies were
      isolated from 50 eyes. There were no significant differences in bacterial species
      or culture positivity rates between study and control eyes. Coagulase-negative
      staphylococcus accounted for 41 of the 58 bacterial colonies (71%). There was a
      63.6% resistance rate to fluoroquinolones among study eyes compared with 32.1%
      among control eyes (P < 0.05). In the subset of 11 study eyes using
      fluoroquinolone drops for 4 days after injection, there was an 87.5% resistance
      rate compared with 25.0% in matched control eyes (P = 0.04). There was no
      significant difference in trimethoprim resistance rates between study and control
      eyes: Four of 14 study eyes (28.6%) showed resistance compared with 5 of 18
      control eyes (27.7%) (P = 1.0). CONCLUSIONS: Use of fluoroquinolone drops after
      intravitreal injection leads to increased rates of resistance among conjunctival
      flora. Repeated use of topical fluoroquinolones after intravitreal injections may
      have a detrimental effect on eye health by breeding resistance in the bacterial
      flora.

PMID- 22420959
TI  - Determinants of anterior chamber depth: the Singapore Chinese Eye Study.
AB  - PURPOSE: Recent advances in anterior segment imaging have enabled the measurement
      of novel ocular biometric parameters, such as lens vault (LV), posterior corneal
      arc length (PCAL), and iris area. The aims of this study were to identify the
      determinants of anterior chamber depth (ACD) and to ascertain the relative
      importance of these determinants in Chinese persons in Singapore. DESIGN:
      Population-based, cross-sectional study. PARTICIPANTS: One thousand sixty Chinese
      participants recruited from the Singapore Chinese Eye Study. METHODS: All
      subjects underwent AS optical coherence tomography (OCT; Carl Zeiss Meditec,
      Dublin, CA). Customized software (Zhongshan Angle Assessment Program, Guangzhou,
      China) was used to measure the AS-OCT parameters. Anterior chamber depth was
      determined using IOLMaster (Carl Zeiss Meditec). Univariate and multivariate
      regression analyses were performed to assess the association between ACD with
      ocular biometric and systemic parameters. A stepwise selection algorithm was used
      to identify sequentially the contribution of each independent variable. MAIN
      OUTCOME MEASURES: Anterior chamber depth and ocular biometric parameters.
      RESULTS: The mean age (+/-standard deviation) of participants was 56.9+/-8.57
      years and 50.5% were men. The mean ACD was 3.24+/-0.35 mm. The strongest
      determinants of ACD were LV (R(2) = 0.582; P<0.001) and PCAL (partial R(2) =
      0.186; P<0.001). For every 10-MUm increase in LV and every 1-mm increase in PCAL,
      ACD changed by -0.008 mm (95% confidence interval [CI], -0.009 to -0.008 mm;
      P<0.001) and 0.525 mm (95% CI, 0.468-0.583 mm; P<0.001), respectively. The 8 most
      highly associated variables (including LV, PCAL, axial length, age, and iris
      area) explained 80.5% of the variability in ACD, but when excluding LV and PCAL,
      the other 6 variables explained only 3.7% of the variability in ACD. After
      controlling for LV and PCAL, axial length was a poor determinant of ACD (partial
      R(2) = 0.006), whereas lens thickness was not associated independently with ACD.
      CONCLUSIONS: Lens vault and PCAL explained 76.8% of the variability in ACD. When
      information about LV and PCAL were available, axial length was a poor determinant
      of ACD, whereas lens thickness was not associated independently with ACD.
      FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest
      in any materials discussed in this article.

PMID- 22420960
TI  - Ocular Whipple's disease: therapeutic strategy and long-term follow-up.
AB  - OBJECTIVE: To characterize the clinical features of ocular Whipple's disease (WD)
      and determine the long-term prognosis after antibiotic treatment. DESIGN:
      Retrospective case series. PARTICIPANTS: Medical records of patients referred
      between January 1993 and December 2010 were reviewed for chronic corticosteroid
      resistant uveitis or neuro-ophthalmologic findings consistent with WD. Eleven
      patients (male/female = 9/2) were included in this study. METHODS: Diagnosis was
      based on cytologic examination and molecular analysis of samples (cerebrospinal
      fluid, vitreous, duodenum, or any involved lymph node). It was based on cytology
      before the routine use of polymerase chain reaction (PCR) and on both cytology
      and molecular biology for more recent patients. Long-term antibiotic therapy
      included oral trimethoprim-sulfamethoxazole (TMP-SMX) and rifampin, TMP-SMX
      alone, rifampin alone, or tetracycline alone. MAIN OUTCOME MEASURES: (1)
      Demographic and clinical characteristics of patients with positive PCR for
      Tropheryma whipplei or periodic acid-Schiff-positive macrophages in the vitreous
      and (2) long-term prognosis after antibiotic treatment. RESULTS: Mean age at
      diagnosis was 63 years (range, 51-73 years). Average time between the onset of
      the disease and diagnosis was 2 years (range, 1 month to 11 years). Mean follow
      up was 7.2 years (range, 0.25-18 years). Ophthalmologic findings consisted of
      chronic uveitis (9 patients), isolated bilateral optic disc swelling (1 patient),
      and Parinaud syndrome (1 patient). All patients had PAS-positive macrophages, and
      6 patients had a positive PCR for T. whipplei. Nine patients were treated with
      TMP-SMX and rifampin. One patient treated with only tetracycline relapsed and was
      successfully treated with TMP-SMX. No major side effects were reported.
      Intraocular inflammation and neurologic manifestations were controlled in all
      cases. At the end of follow-up, 2 patients were off treatment, 2 patients had a
      neurologic relapse after treatment interruption, and 5 patients were still taking
      TMP-SMX. One patient was taking only rifampin. Two patients were lost to follow
      up. CONCLUSIONS: Ocular WD seems to be a neurologic manifestation of WD.
      Trimethoprim-SMX with rifampin is an efficient treatment, and prolonging
      treatment for at least 1 year is recommended. Long-term low-dose antibiotic
      therapy may reduce the rate of relapse, neurologic involvement, and death.

PMID- 22420961
TI  - Interleukin (IL)-22 serum level in hypersensitivity pneumonitis (HP) in a
      mushroom worker.

PMID- 22420962
TI  - Treatment outcomes, growth height, and neuroendocrine functions in patients with
      intracranial germ cell tumors treated with chemoradiation therapy.
AB  - PURPOSE: We carried out a retrospective review of patients receiving
      chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower
      dose than those previously reported. To identify an optimal GCT treatment
      strategy, we evaluated treatment outcomes, growth height, and neuroendocrine
      functions. METHODS AND MATERIALS: Twenty-two patients with GCT, including 4
      patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age
      at initial diagnosis was 11.5 years (range, 6-19 years). Seventeen patients
      initially received whole brain irradiation (median dose, 19.8 Gy), and 5
      patients, including 4 with NGGCT, received craniospinal irradiation (median dose,
      30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for
      pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the
      hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. RESULTS:
      The median follow-up time was 72 months (range, 18-203 months). The rates of both
      disease-free survival and overall survival were 100%. The standard deviation
      scores (SDSs) of final heights recorded at the last assessment tended to be lower
      than those at initial diagnosis. Even in all 5 patients with tumors located away
      from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors
      adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic
      obesity and/or growth hormone deficiency, and 13 had other pituitary hormone
      deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not
      show any neuroendocrine dysfunctions except for a tendency to short stature.
      CONCLUSIONS: CRT for GCT using limited radiation doses resulted in excellent
      treatment outcomes. Even after limited radiation doses, insufficient growth
      height was often observed that was independent of tumor location. Our study
      suggests that close follow-up of neuroendocrine functions, including growth
      hormone, is essential for all patients with GCT.

PMID- 22420963
TI  - Expression of EGFR under tumor hypoxia: identification of a subpopulation of
      tumor cells responsible for aggressiveness and treatment resistance.
AB  - PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) and tumor
      hypoxia have been shown to correlate with worse outcome in several types of
      cancer including head-and-neck squamous cell carcinoma. Little is known about the
      combination and possible interactions between the two phenomena. METHODS AND
      MATERIALS: In this study, 45 cases of histologically confirmed squamous cell
      carcinomas of the head and neck were analyzed. All patients received intravenous
      infusions of the exogenous hypoxia marker pimonidazole prior to biopsy. Presence
      of EGFR, pimonidazole binding, and colocalization between EGFR and tumor hypoxia
      were examined using immunohistochemistry. RESULTS: Of all biopsies examined,
      respectively, 91% and 60% demonstrated EGFR- and pimonidazole-positive areas. A
      weak but significant association was found between the hypoxic fractions of
      pimonidazole (HFpimo) and EGFR fractions (F-EGFR) and between F-EGFR and relative
      vascular area. Various degrees of colocalization between hypoxia and EGFR were
      found, increasing with distance from the vasculature. A high fraction of EGFR was
      correlated with better disease-free and metastasis-free survival, whereas a high
      degree of colocalization correlated with poor outcome. CONCLUSIONS:
      Colocalization of hypoxia and EGFR was demonstrated in head-and-neck squamous
      cell carcinomas, predominantly at longer distances from vessels. A large amount
      of colocalization was associated with poor outcome, which points to a survival
      advantage of hypoxic cells that are also able to express EGFR. This subpopulation
      of tumor cells might be indicative of tumor aggressiveness and be partly
      responsible for treatment resistance.

PMID- 22420964
TI  - Changes in pulmonary function after three-dimensional conformal radiotherapy,
      intensity-modulated radiotherapy, or proton beam therapy for non-small-cell lung
      cancer.
AB  - PURPOSE: To investigate the extent of change in pulmonary function over time
      after definitive radiotherapy for non-small-cell lung cancer (NSCLC) with modern
      techniques and to identify predictors of changes in pulmonary function according
      to patient, tumor, and treatment characteristics. PATIENTS AND METHODS: We
      analyzed 250 patients who had received >= 60 Gy radio(chemo)therapy for primary
      NSCLC in 1998-2010 and had undergone pulmonary function tests before and within 1
      year after treatment. Ninety-three patients were treated with three-dimensional
      conformal radiotherapy, 97 with intensity-modulated radiotherapy, and 60 with
      proton beam therapy. Postradiation pulmonary function test values were evaluated
      among individual patients compared with the same patient's preradiation value at
      the following time intervals: 0-4 (T1), 5-8 (T2), and 9-12 (T3) months. RESULTS:
      Lung diffusing capacity for carbon monoxide (DLCO) was reduced in the majority of
      patients along the three time periods after radiation, whereas the forced
      expiratory volume in 1 s per unit of vital capacity (FEV1/VC) showed an increase
      and decrease after radiation in a similar percentage of patients. There were
      baseline differences (stage, radiotherapy dose, concurrent chemotherapy) among
      the radiation technology groups. On multivariate analysis, the following features
      were associated with larger posttreatment declines in DLCO: pretreatment DLCO,
      gross tumor volume, lung and heart dosimetric data, and total radiation dose.
      Only pretreatment DLCO was associated with larger posttreatment declines in
      FEV1/VC. CONCLUSIONS: Lung diffusing capacity for carbon monoxide is reduced in
      the majority of patients after radiotherapy with modern techniques. Multiple
      factors, including gross tumor volume, preradiation lung function, and dosimetric
      parameters, are associated with the DLCO decline. Prospective studies are needed
      to better understand whether new radiation technology, such as proton beam
      therapy or intensity-modulated radiotherapy, may decrease the pulmonary
      impairment through greater lung sparing.

PMID- 22420965
TI  - Radiotherapy improves survival in unresected stage I-III bronchoalveolar
      carcinoma.
AB  - PURPOSE: To test the hypothesis that radiotherapy (RT) improves the outcome of
      patients with unresected, nonmetastatic bronchoalveolar carcinoma (BAC) by
      performing a population-based analysis within the Surveillance, Epidemiology, and
      End Results (SEER) registry. METHODS AND MATERIALS: Inclusion criteria were as
      follows: patients diagnosed with BAC, Stage I-III, between 2001 and 2007.
      Exclusion criteria included unknown stage, unknown primary treatment modality,
      Stage IV disease, and those diagnosed at autopsy. Demographic data, treatment
      details, and overall survival were retrieved from the SEER database. Survival was
      analyzed using the Kaplan-Meier method and log-rank test. RESULTS: A total of
      6933 patients with Stage I-III BAC were included in the analysis. The median age
      at diagnosis was 70 years (range, 10-101 years). The majority of patients were
      diagnosed with Stage I (74.4%); 968 patients (14%) did not undergo surgical
      resection. Unresected patients were more likely to be older (p < 0.0001), male (p
      = 0.001), black (p < 0.0001), and Stage III (p < 0.0001). Within the cohort of
      unresected patients, 300 (31%) were treated with RT. The estimated 2-year overall
      survival for patients with unresected, nonmetastatic BAC was 58%, 44%, and 27% in
      Stage I, II, and III, respectively. Factors associated with improved survival
      included female sex, earlier stage at diagnosis, and use of RT. Median survival
      in those not receiving RT vs. receiving RT was as follows: Stage I, 28 months vs.
      33 months (n = 364, p = 0.06); Stage II, 18 months vs. not reached (n = 31,
      nonsignificant); Stage III, 10 months vs. 17 months (n = 517, p < 0.003).
      CONCLUSIONS: The use of RT is associated with improved prognosis in unresected
      Stage I-III BAC. Less than a third of patients who could have potentially
      benefited from RT received it, suggesting that the medical specialists involved
      in the care of these patients underappreciate the importance of RT.

PMID- 22420966
TI  - A novel Peptide to treat oral mucositis blocks endothelial and epithelial cell
      apoptosis.
AB  - PURPOSE: No effective agents currently exist to treat oral mucositis (OM) in
      patients receiving chemoradiation for the treatment of head-and-neck cancer. We
      identified a novel 21-amino acid peptide derived from antrum mucosal protein-18
      that is cytoprotective, mitogenic, and motogenic in tissue culture and animal
      models of gastrointestinal epithelial cell injury. We examined whether
      administration of antrum mucosal protein peptide (AMP-p) could protect against
      and/or speed recovery from OM. METHODS AND MATERIALS: OM was induced in
      established hamster models by a single dose of radiation, fractionated radiation,
      or fractionated radiation together with cisplatin to simulate conventional
      treatments of head-and-neck cancer. RESULTS: Daily subcutaneous administration of
      AMP-p reduced the occurrence of ulceration and accelerated mucosal recovery in
      all three models. A delay in the onset of erythema after irradiation was
      observed, suggesting that a protective effect exists even before injury to
      mucosal epithelial cells occurs. To test this hypothesis, the effects of AMP-p on
      tumor necrosis factor-alpha-induced apoptosis were studied in an endothelial cell
      line (human dermal microvascular endothelial cells) as well as an epithelial cell
      line (human adult low-calcium, high-temperature keratinocytes; HaCaT) used to
      model the oral mucosa. AMP-p treatment, either before or after cell monolayers
      were exposed to tumor necrosis factor-alpha, protected against development of
      apoptosis in both cell types when assessed by annexin V and propidium iodide
      staining followed by flow cytometry or ligase-mediated polymerase chain reaction.
      CONCLUSIONS: These observations suggest that the ability of AMP-p to attenuate
      radiation-induced OM could be attributable, at least in part, to its
      antiapoptotic activity.

PMID- 22420967
TI  - Survival after chemoradiation in resected pancreatic cancer: the impact of
      adjuvant gemcitabine.
AB  - PURPOSE: To evaluate survival in patients with resected pancreatic cancer treated
      with concurrent chemoradiation with or without adjuvant gemcitabine (Gem).
      METHODS AND MATERIALS: From 1998 to 2010, 86 patients with pancreatic
      adenocarcinoma who underwent resection were treated with adjuvant concurrent
      chemoradiation. Thirty-four patients received concurrent 5-fluorouracil-based
      chemoradiation (5-FU/RT) with traditional field radiation (range, 45-61.2 Gy;
      median, 50.4 Gy) without further adjuvant therapy. Thirty patients received
      traditional field 5-FU/RT (range, 45-60.4 Gy; median, 50.4 Gy) with Gem (1,000
      mg/m(2) weekly) either before and after radiotherapy or only after radiotherapy.
      Twenty-two patients received concurrent full-dose Gem (1,000 mg/m(2) weekly)
      based chemoradiation (Gem/RT), consisting of involved-field radiation (range, 27
      38 Gy; median, 36 Gy) followed by further adjuvant Gem. RESULTS: The median age
      of the cohort was 65 years (range, 40-80 years). Of the patients, 58 had T3
      tumors (67%), 22 had T2 tumors (26%), and 6 had T1 tumors (7%). N1 disease was
      present in 61 patients (71%), whereas 18 patients (21%) had R1 resections.
      Performance status, lymph node status, and margin status were all similar among
      the treatment groups. Median follow-up was 19.0 months. Median overall survival
      (OS) (19.2 months, 19.0 months, and 21.0 months) and 3-year OS rates (26.5%,
      27.2%, and 32.1%) were similar among patients with 5-FU/RT with no adjuvant Gem,
      those with 5-FU/RT with adjuvant Gem, and those with Gem/RT with adjuvant Gem,
      respectively (p = 0.88). Patients who received adjuvant Gem had a similar median
      OS (22.1 months) and 3-year OS rate (29%) compared to patients who did not (19.2
      months and 26.5%, respectively) (p = 0.62). There was a trend for improved 3-year
      OS rates in patients with R0 vs. R1 resections (28.1% vs. 14.2%, p = 0.06) and in
      patients with T1 and T2 vs. T3 tumors (38% vs. 20%, p = 0.09). Node-negative
      patients had an improved 3-year OS rate (30.1%) when compared with patients with
      N1 disease (16.2%) (p = 0.02). CONCLUSION: In our cohort of patients with
      resected pancreatic cancer, Gem chemotherapy did not improve OS after
      chemoradiotherapy.

PMID- 22420968
TI  - Phase measurement of cognitive impairment specific to radiotherapy.
AB  - PURPOSE: Memory impairment is an early-delayed effect of radiotherapy (RT). The
      prospective longitudinal measurement of the cognitive phase effects from RT was
      conducted on treated and untreated brain tumor patients. The study design
      investigated semantic vs. perceptual and visual vs. verbal memory to determine
      the most disease-specific measure of RT-related changes and understanding of the
      neurotoxicity from RT to the brain. METHODS AND MATERIALS: Tests of memory that
      had previously shown RT-related phasic changes were compared with experimental
      tests of memory to test hypotheses about cognition targeted to the neural
      toxicity of RT. The results from 41 irradiated and 29 nonirradiated patients with
      low-grade, supratentorial tumors were analyzed. The methods controlled for
      comorbid white matter risk, recurrence, interval after treatment, and age (18-69
      years). The effects were examined before RT and at three points after RT to 1
      year using a mixed effects model that included interval, group, surgical status,
      medication use, practice, and individual random effects. Four new tests of memory
      and other candidate cognitive tests were investigated, and a post hoc analysis of
      a comprehensive battery of tests was performed to identify the cognitive
      processes most specific to RT. RESULTS: The RT effects on memory were identified
      in the treated group only; among the new tests of memory and the complete
      neurocognitive battery, the RT effects were significant only for delayed recall
      (p < 0.009) and interval to recognize (p < 0.002). Tumor location was not related
      to the treatment effect. Memory decline was specific to retrieval of semantic
      memories; a double dissociation of semantic from perceptual visual memory was
      demonstrated in the RT group. CONCLUSIONS: These results implicate memory
      dependent on the semantic cortex and the hippocampal memory system. A cognitive
      measurement that is brief but specific to neural mechanisms is effective and
      feasible for studies of RT damage.

PMID- 22420969
TI  - A 2011 updated systematic review and clinical practice guideline for the
      management of malignant extradural spinal cord compression.
AB  - PURPOSE: To update the 2005 Cancer Care Ontario practice guidelines for the
      diagnosis and treatment of adult patients with a suspected or confirmed diagnosis
      of extradural malignant spinal cord compression (MESCC). METHODS: A review and
      analysis of data published from January 2004 to May 2011. The systematic
      literature review included published randomized control trials (RCTs), systematic
      reviews, meta-analyses, and prospective/retrospective studies. RESULTS: An RCT of
      radiation therapy (RT) with or without decompressive surgery showed improvements
      in pain, ambulatory ability, urinary continence, duration of continence,
      functional status, and overall survival. Two RCTs of RT (30 Gy in eight fractions
      vs. 16 Gy in two fractions; 16 Gy in two fractions vs. 8 Gy in one fraction) in
      patients with a poor prognosis showed no difference in ambulation, duration of
      ambulation, bladder function, pain response, in-field failure, and overall
      survival. Retrospective multicenter studies reported that protracted RT schedules
      in nonsurgical patients with a good prognosis improved local control but had no
      effect on functional or survival outcomes. CONCLUSIONS: If not medically
      contraindicated, steroids are recommended for any patient with neurologic
      deficits suspected or confirmed to have MESCC. Surgery should be considered for
      patients with a good prognosis who are medically and surgically operable. RT
      should be given to nonsurgical patients. For those with a poor prognosis, a
      single fraction of 8 Gy should be given; for those with a good prognosis, 30 Gy
      in 10 fractions could be considered. Patients should be followed up clinically
      and/or radiographically to determine whether a local relapse develops. Salvage
      therapies should be introduced before significant neurologic deficits occur.

PMID- 22420970
TI  - Low-dose radiation treatment in pulmonary mucosa-associated lymphoid tissue
      lymphoma: a plausible approach? A single-institution experience in 10 patients.
AB  - PURPOSE: To propose an alternative approach for treatment of pulmonary marginal
      zone lymphoma, using a very small radiation dose (2 * 2 Gy) delivered exclusively
      to tumor sites. METHODS AND MATERIALS: Patients had localized pulmonary mucosa
      associated lymphoid tissue (MALT) lymphoma according to the World Health
      Organization classification. The 6-MV radiation treatments were delivered using
      tumor-limited fields, except in cases of diffuse bilateral involvement. Two daily
      fractions of 2 Gy were delivered to tumor-limited fields using a 6-MV linear
      accelerator. RESULTS: Ten patients with pulmonary MALT lymphoma entered the
      study. All but 1 had localized tumor masses. The median follow-up was 56 months
      (range, 2-103 months). Complete remission or an unconfirmed complete remission
      was obtained in 60% of patients within the first 2 months, and two additional
      partial responses were converted into a long-term unconfirmed complete remission.
      All patients are well and alive, no local progression was observed, and the 5
      year progression-free survival rate was 87.5% (95% confidence interval 49%-97%).
      CONCLUSIONS: Our results suggest that extremely low radiation doses delivered
      exclusively to tumor sites might be a treatment option in pulmonary MALT
      lymphoma.

PMID- 22420971
TI  - A multimodal approach including craniospinal irradiation improves the treatment
      outcome of high-risk intracranial nongerminomatous germ cell tumors.
AB  - PURPOSE: To evaluate whether a multimodal approach including craniospinal
      irradiation (CSI) improves treatment outcome in nongerminomatous germ cell tumor
      (NGGCT) patients. METHODS AND MATERIALS: We reviewed the records of 32 patients
      with NGGCTs. Fourteen patients belonged to the intermediate prognosis group
      (immature teratoma, teratoma with malignant transformation, and mixed tumors
      mainly composed of germinoma or teratoma), and 18 patients belonged to the poor
      prognosis group (other highly malignant tumors). Patients with pure germinoma or
      mature teratoma were excluded from this study. Nineteen patients were treated
      with a combination of surgery, chemotherapy, and radiotherapy (RT); 9 patients
      received chemotherapy plus RT; 3 patients received surgery plus RT; and 1 patient
      received RT alone. Twenty-seven patients received CSI with a median of 36 Gy
      (range, 20-41 Gy) plus focal boost of 18-30.6 Gy, and 5 patients received whole
      brain RT (WBRT) (20-36 Gy) or focal RT (50.4-54 Gy). The rate of total and
      subtotal resection was 71.9%. The median follow-up for surviving patients was 121
      months. RESULTS: Treatment failed in 7 patients. Three of the 5 patients who
      received focal RT or WBRT had local failure. Four cerebrospinal fluid (CSF)
      failures occurred after CSI. No failure occurred in the intermediate prognosis
      group. Ten-year recurrence-free survival (RFS) and overall survival (OS) for all
      patients were 77.6% and 74.6%, respectively. Ten-year RFS for the intermediate
      and poor prognosis groups were 100% and 61.1%, respectively (p = 0.012). OS for
      the two groups were 85.1% and 66.7%, respectively (p = 0.215). Tumor histology
      and CSI were significant prognostic factors for RFS, and CSI was significantly
      associated with OS. CONCLUSIONS: A multimodal approach was effective for treating
      NGGCTs. CSI should be considered for patients with poor prognostic histology.

PMID- 22420972
TI  - Impact of consolidation radiation therapy in stage III-IV diffuse large B-cell
      lymphoma with negative post-chemotherapy radiologic imaging.
AB  - PURPOSE: While consolidation radiation therapy (i.e., RT administered after
      chemotherapy) is routine treatment for patients with early-stage diffuse large B
      cell lymphoma (DLBCL), the role of consolidation RT in stage III-IV DLBCL is
      controversial. METHODS AND MATERIALS: Cases of patients with stage III-IV DLBCL
      treated from 1991 to 2009 at Duke University, who achieved a complete response to
      chemotherapy were reviewed. Clinical outcomes were calculated using the Kaplan
      Meier method and were compared between patients who did and did not receive RT,
      using the log-rank test. A multivariate analysis was performed using Cox
      proportional hazards model. RESULTS: Seventy-nine patients were identified.
      Chemotherapy (median, 6 cycles) consisted of anti-CD20 antibody rituximab
      combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP;
      65%); cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; 22%); or
      other (13%). Post-chemotherapy imaging consisted of positron emission tomography
      (PET)/computed tomography (CT) (73%); gallium with CT (14%); or CT only (13%).
      Consolidation RT (median, 25 Gy) was given to involved sites of disease in 38
      (48%) patients. Receipt of consolidation RT was associated with improved in-field
      control (92% vs. 69%, respectively, p = 0.028) and event-free survival (85% vs.
      65%, respectively, p = 0.014) but no difference in overall survival (85% vs. 78%,
      respectively, p = 0.15) when compared to patients who did not receive
      consolidation RT. On multivariate analysis, no RT was predictive of increased
      risk of in-field failure (hazard ratio [HR], 8.01, p = 0.014) and worse event
      free survival (HR, 4.3, p = 0.014). CONCLUSIONS: Patients with stage III-IV DLBCL
      who achieve negative post-chemotherapy imaging have improved in-field control and
      event-free survival with low-dose consolidation RT.

PMID- 22420973
TI  - Stimulation of hepatoma cell invasiveness and metastatic potential by proteins
      secreted from irradiated nonparenchymal cells.
AB  - PURPOSE: To determine whether factors secreted by irradiated liver nonparenchymal
      cells (NPCs) may influence invasiveness and/or metastatic potential of
      hepatocellular carcinoma (HCC) cells and to elucidate a possible mechanism for
      such effect. METHODS AND MATERIALS: Primary rat NPCs were cultured and divided
      into irradiated (10-Gy X-ray) and nonirradiated groups. Forty-eight hours after
      irradiation, conditioned medium from irradiated (SR) or nonirradiated (SnonR)
      cultures were collected and added to sublethally irradiated cultures of the
      hepatoma McA-RH7777 cell line. Then, hepatoma cells were continuously passaged
      for eight generations (RH10Gy-SR and RH10Gy-SnonR). The invasiveness and
      metastatic potential of McA-RH7777, RH10Gy-SnonR, and RH10Gy-SR cells were
      evaluated using an in vitro gelatinous protein (Matrigel) invasion and an in vivo
      metastasis assay. In addition, SR and SnonR were tested using rat cytokine
      antibody arrays and enzyme-linked immunosorbent assay (ELISA). RESULTS: In vitro
      gelatinous protein invasion assay indicated that the numbers of invading cells
      was significantly higher in RH10Gy-SR (40 +/- 4.74) than in RH10Gy-SnonR (30.6 +/
      3.85) cells, and lowest in McA-RH7777 (11.4 +/- 3.56) cells. The same pattern
      was observed in vivo in a lung metastasis assay, as evaluated by number of
      metastatic lung nodules seen with RH10Gy-SR (28.83 +/- 5.38), RH10Gy-SnonR (22.17
      +/- 4.26), and McA-RH7777 (8.3 +/- 3.8) cells. Rat cytokine antibody arrays and
      ELISA demonstrated that metastasis-promoting cytokines (tumor necrosis factor
      alpha and interleukin-6), circulating growth factors (vascular endothelial growth
      factor and epidermal growth factor), and metalloproteinases (MMP-2 and MMP-9)
      were upregulated in SR compared with SnonR. CONCLUSIONS: Radiation can increase
      invasiveness and metastatic potential of sublethally irradiated hepatoma cells,
      and soluble mediators released from irradiated NPCs promote this potential.
      Increased secretion of metastasis-related cytokines and factors from NPCs after
      irradiation may be a possible mechanism for the radiation-induced invasiveness
      and metastatic potential of HCC.

PMID- 22420974
TI  - Racial inequities in receipt of influenza vaccination among nursing home
      residents in the United States, 2008-2009: a pattern of low overall coverage in
      facilities in which most residents are black.
AB  - OBJECTIVES: Nationwide among nursing home residents, receipt of the influenza
      vaccine is 8 to 9 percentage points lower among blacks than among whites. The
      objective of this study was to determine if the national inequity in vaccination
      is because of the characteristics of facilities and/or residents. DESIGN: Cross
      sectional study with multilevel modeling. SETTING AND PARTICIPANTS: States in
      which 1% or more of nursing home residents were black and the difference in
      influenza vaccination coverage between white and black nursing home residents was
      1 percentage point or higher (n = 39 states and the District of Columbia). Data
      on residents (n = 2,359,321) were obtained from the Centers for Medicare &
      Medicaid Service's Minimum Data Set for October 1, 2008, through March 31, 2009.
      MEASUREMENTS: Residents' influenza vaccination status (vaccinated, refused
      vaccine, or not offered vaccination). RESULTS: States with higher overall
      influenza vaccination coverage among nursing home residents had smaller racial
      inequities. In nursing homes with higher proportions of black residents,
      vaccination coverage was lower for both blacks and whites. The most dramatic
      inequities existed between whites in nursing homes with 0% blacks (L1) and blacks
      in nursing homes with 50% or more blacks (L5) in states with overall racial
      inequities of 10 percentage points or more. In these states, more black nursing
      home residents lived in nursing homes with 50% or more blacks (L5); in general,
      the same homes with low overall coverage. CONCLUSION: Inequities in influenza
      vaccination coverage among nursing home residents are largely because of low
      vaccination coverage in nursing homes with a high proportion of black residents.
      Findings indicate that implementation of culturally appropriate interventions to
      increase vaccination in facilities with larger proportions of black residents may
      reduce the racial gap in influenza vaccination as well as increase overall state
      level vaccination.

PMID- 22420976
TI  - Structural characterization of microcin E492 amyloid formation: Identification of
      the precursors.
AB  - Microcin E492 is a low-molecular weight, channel-forming bacteriotoxin that
      generates amyloid structures. Using electron microscopy and image processing
      techniques several structural conformations can be observed. Prior to the
      conditions that induce amyloid formation and at its initial stage, microcin E492
      molecules can be found in two main types of oligomers: a pentameric, pore-like
      structure consisting of globular monomers of ~25A diameter, and long filaments
      made up of stacked pentamers. The equilibrium between these structures depends on
      the properties of the solvent, because samples kept in methanol mainly show the
      pentameric structure. Amyloid induction in aqueous solvent reveals the presence,
      together with the above mentioned structures, of several amyloid structures such
      as flat and helical filaments. In addition, X-ray diffraction analysis
      demonstrated that the fibrils formed by microcin E492 presented cross-beta
      structure, a distinctive property of amyloid fibrils. Based on the study of the
      observed structures we propose that microcin E492 has two conformations: a native
      one that assembles mainly into a pentameric structure, which functions as a pore,
      and an amyloid conformation which results in the formation of different types of
      amyloid filaments.

PMID- 22420977
TI  - High-throughput subtomogram alignment and classification by Fourier space
      constrained fast volumetric matching.
AB  - Cryo-electron tomography allows the visualization of macromolecular complexes in
      their cellular environments in close-to-live conditions. The nominal resolution
      of subtomograms can be significantly increased when individual subtomograms of
      the same kind are aligned and averaged. A vital step for such a procedure are
      algorithms that speedup subtomogram alignment and improve its accuracy to allow
      reference-free subtomogram classifications. Such methods will facilitate
      automation of tomography analysis and overall high throughput in the data
      processing. Building on previous work, here we propose a fast rotational
      alignment method that uses the Fourier equivalent form of a popular constrained
      correlation measure that considers missing wedge corrections and density
      variances in the subtomograms. The fast rotational search is based on 3D
      volumetric matching, which improves the rotational alignment accuracy in
      particular for highly distorted subtomograms with low SNR and tilt angle ranges
      in comparison to fast rotational matching of projected 2D spherical images. We
      further integrate our fast rotational alignment method in a reference-free
      iterative subtomogram classification scheme, and propose a local feature
      enhancement strategy in the classification process. As a proof of principle, we
      can demonstrate that the automatic method can successfully classify a large
      number of experimental subtomograms without the need of a reference structure.

PMID- 22420978
TI  - Effect of prolyl hydroxylase domain-2 haplodeficiency on the hepatocarcinogenesis
      in mice.
AB  - BACKGROUND & AIMS: The two major primary liver cancers in adults are
      hepatocellular carcinoma and cholangiocarcinoma. These tumors rapidly outgrow
      their vascular supply and become hypoxic, resulting in the production of hypoxia
      inducible factors. Recently, interest has grown in the regulators of these
      factors. Several reports have been published describing the role of prolyl
      hydroxylase domains--the key oxygen sensor responsible for the degradation of
      hypoxia inducible factors--tumor progression and vascularisation. The effect of
      prolyl hydroxylase domain 2 on the pathogenesis of liver cancer has never been
      studied. METHODS: A diethylnitrosamine-induced mouse model was used in this
      study, allowing primary hepatic tumors to occur as a result of chronic liver
      damage. Several parameters of prolyl hydroxylase domain 2-haplodeficient mice
      were compared to those of wild type mice, thereby focussing on the expression of
      angiogenic factors and on the hepatic progenitor cell activation and
      differentiation. RESULTS: This study shows that inhibiting prolyl hydroxylase
      domain 2 increases the hepatocarcinogenesis and stimulates the development of
      cholangiocarcinoma. Furthermore, PHD2 deficiency and the accompanying continuous
      HIF activation, selected for a more metastatic tumor phenotype. CONCLUSIONS: The
      effect of prolyl hydroxylase domain 2 deficiency on hepatocarcinogenesis hold a
      great potential for therapeutic intervention, since hypoxia and the selection for
      a more aggressive cholangiocarcinoma phenotype might also have a repercussion on
      patients receiving long-term treatment with anti-angiogenic compounds.

PMID- 22420979
TI  - Are common factors involved in the pathogenesis of primary liver cancers? A meta
      analysis of risk factors for intrahepatic cholangiocarcinoma.
AB  - BACKGROUND & AIMS: Well established risk factors for intrahepatic
      cholangiocarcinoma such as biliary tract inflammation and liver flukes are not
      present in most Western countries patients. Although cirrhosis and other causes
      of chronic liver disease have been implicated, their contribution as risk factors
      for cholangiocarcinoma is unclear and our aims were to analyze these emerging
      potential risk factors by systematic examination of case-control series from
      geographically diverse regions. METHODS: We performed a literature review and
      meta-analysis of case-control studies on intrahepatic cholangiocarcinoma and
      cirrhosis and related risk factors. Tests of heterogeneity, publication bias and
      sensitivity analyses were performed and an overall odds ratio and 95% confidence
      intervals calculated. RESULTS: Eleven studies from both high and low prevalence
      regions were identified. All studies except those evaluating cirrhosis, diabetes,
      and obesity exhibited significant heterogeneity. Cirrhosis was associated with a
      combined OR of 22.92 (95% CI=18.24-28.79). Meta-analysis estimated the overall
      odds ratio (with 95% confidence intervals) for defined risk factors such as
      hepatitis B: 5.10 (2.91-8.95), hepatitis C: 4.84 (2.41-9.71), obesity: 1.56 (1.26
      1.94), diabetes mellitus type II: 1.89 (1.74-2.07), smoking: 1.31 (0.95-1.82),
      and alcohol use: 2.81 (1.52-5.21). Sensitivity analysis did not alter the odds
      ratio for any risk factors except smoking and there was no evidence of
      publication bias. CONCLUSIONS: Cirrhosis, chronic hepatitis B and C, alcohol use,
      diabetes, and obesity are major risk factors for intrahepatic cholangiocarcinoma.
      These data suggest a common pathogenesis of primary intrahepatic epithelial
      cancers.

PMID- 22420982
TI  - Infant feeding: the effects of scheduled vs. on-demand feeding on mothers'
      wellbeing and children's cognitive development.
AB  - BACKGROUND: Many popular childcare books recommend feeding babies to a schedule,
      but no large-scale study has ever examined the effects of schedule-feeding. Here,
      we examine the relationship between feeding infants to a schedule and two sets of
      outcomes: mothers' wellbeing, and children's longer-term cognitive and academic
      development. METHODS: We used a sample of 10,419 children from the Avon
      Longitudinal Study of Parents and Children, a cohort study of children born in
      the 1990 s in Bristol, UK. Outcomes were compared by whether babies were fed to a
      schedule at 4 weeks. Maternal wellbeing indicators include measures of sleep
      sufficiency, maternal confidence and depression, collected when babies were
      between 8 weeks and 33 months. Children's outcomes were measured by standardized
      tests at ages 5, 7, 11 and 14, and by IQ tests at age 8. RESULTS: Mothers who fed
      to a schedule scored more favourably on all wellbeing measures except depression.
      However, schedule-fed babies went on to do less well academically than their
      demand-fed counterparts. After controlling for a wide range of confounders,
      schedule-fed babies performed around 17% of a standard deviation below demand-fed
      babies in standardized tests at all ages, and 4 points lower in IQ tests at age 8
      years. CONCLUSIONS: Feeding infants to a schedule is associated with higher
      levels of maternal wellbeing, but with poorer cognitive and academic outcomes for
      children.

PMID- 22420983
TI  - Peptide receptor radionuclide therapy in the United States.

PMID- 22420981
TI  - Recording and analysis techniques for high-frequency oscillations.
AB  - In recent years, new recording technologies have advanced such that, at high
      temporal and spatial resolutions, high-frequency oscillations (HFO) can be
      recorded in human partial epilepsy. However, because of the deluge of
      multichannel data generated by these experiments, achieving the full potential of
      parallel neuronal recordings depends on the development of new data mining
      techniques to extract meaningful information relating to time, frequency and
      space. Here, we aim to bridge this gap by focusing on up-to-date recording
      techniques for measurement of HFO and new analysis tools for their quantitative
      assessment. In particular, we emphasize how these methods can be applied, what
      property might be inferred from neuronal signals, and potentially productive
      future directions.

PMID- 22420980
TI  - Mechanisms of physiological and epileptic HFO generation.
AB  - High frequency oscillations (HFO) have a variety of characteristics: band-limited
      or broad-band, transient burst-like phenomenon or steady-state. HFOs may be
      encountered under physiological or under pathological conditions (pHFO). Here we
      review the underlying mechanisms of oscillations, at the level of cells and
      networks, investigated in a variety of experimental in vitro and in vivo models.
      Diverse mechanisms are described, from intrinsic membrane oscillations to network
      processes involving different types of synaptic interactions, gap junctions and
      ephaptic coupling. HFOs with similar frequency ranges can differ considerably in
      their physiological mechanisms. The fact that in most cases the combination of
      intrinsic neuronal membrane oscillations and synaptic circuits are necessary to
      sustain network oscillations is emphasized. Evidence for pathological HFOs,
      particularly fast ripples, in experimental models of epilepsy and in human
      epileptic patients is scrutinized. The underlying mechanisms of fast ripples are
      examined both in the light of animal observations, in vivo and in vitro, and in
      epileptic patients, with emphasis on single cell dynamics. Experimental
      observations and computational modeling have led to hypotheses for these
      mechanisms, several of which are considered here, namely the role of out-of-phase
      firing in neuronal clusters, the importance of strong excitatory AMPA-synaptic
      currents and recurrent inhibitory connectivity in combination with the fast time
      scales of IPSPs, ephaptic coupling and the contribution of interneuronal coupling
      through gap junctions. The statistical behaviour of fast ripple events can
      provide useful information on the underlying mechanism and can help to further
      improve classification of the diverse forms of HFOs.

PMID- 22420984
TI  - [Evidence-based protocol on the urinary catheter cares in intensive care units].
AB  - Urinary Tract Infections (UTIs) account for 24.92% of ICU nosocomial infections
      investigated. They are associated with increased morbidity and mortality,
      increased hospital stay and hospital costs, jeopardizing patient safety.
      Prevalence of UTI in ICU is directly related to the widespread use of urethral
      catheter (UC). It has been estimated that between 17% and 69% of UTIs associated
      with the UC can be prevented through an evidence-based prevention program. The
      Centers for Disease Control and Prevention recommend, based on strong evidence
      for its implementation, the use of packages based on evidence and ongoing
      training of health personnel in the extrinsic risk factors of UTI associated with
      UC-related nursing care (technique of insertion, maintenance and drainage
      system). The development of an evidence-based UC protocol of care for, dealt with
      in the latest clinical guidelines, and the systematic reviews extracted from the
      Cochrane, where the clinical cares that are most clearly shown to have a direct
      relation to decrease of UTI asssociated with UC are described, will make it
      possible for us to reach a consensus on the guidelines of our care to avoid their
      variability. This will also make it possible to evaluate and compare the quality
      of our cares with other ICUs, using quality indicators established by the
      National Surveillance Study of Nosocomial Infection in Medical Services
      Intensive.

PMID- 22420985
TI  - [Stroke care, conclusions based on results].

PMID- 22420986
TI  - Epigenetic therapy with hydralazine and magnesium valproate reverses imatinib
      resistance in patients with chronic myeloid leukemia.
AB  - The epigenetic drugs hydralazine and valproate were administered in a
      compassionate manner to 8 patients with chronic myeloid leukemia (CML) refractory
      to imatinib. Two patients had a complete hematologic response (25%),1 major
      cytogenetic response, 1 complete cytogenetic response (25% any cytogenetic
      response), and 3 (37.5%)stable disease. No grade 3 or 4 toxicity was observed.
      These results show the ability of epigenetic therapy to revert imatinib
      resistance. BACKGROUND: Epigenetic alterations participate in the development of
      acquired resistance to imatinib, hence, the DNA methylation, and histone
      deacetylase inhibitors hydralazine and valproate, respectively, has the potential
      to overcome it. PATIENT AND METHODS: A series of 8 patients with chronic myeloid
      leukemia (CML) refractory to imatinib mesylate with no access to second
      generation tyrosine kinase inhibitors were treated with hydralazine and valproate
      in a compassionate manner. Clinical efficacy and safety of these drugs added to
      imatinib mesylate were evaluated. RESULTS: Two patients were in the blast phase,
      5 were in the accelerated phase, and 1 was in the chronic phase. All the patients
      continued with the same dose of imatinib that they had been receiving at the time
      of development of resistance, with a median dose of 600 mg daily (range, 400-800
      mg). The median time from diagnosis of CML to the start of hydralazine and
      valproate was 53.6 months (range, 19-84 months). Two (25%) patients had a
      complete hematologic response, one (12.5%) had an major cytogenetic response, and
      one (12.5%) had a complete cytogenetic response. Three (37.5%) patients had
      stable disease, and only one (12.5%) patient failed to respond. At a median
      follow-up time of 18 months (range, 3-18 months), the median survival had not
      been reached, and the projected overall survival was 63%. All the patients had
      mild neurologic toxicity, including distal tremor and somnolence. No grade 3 or 4
      toxicity was observed. CONCLUSIONS: Our results suggest that the epigenetic drugs
      hydralazine and valproate revert the resistance to imatinib in patients with CML.

PMID- 22420987
TI  - Energy requirement for alkali assisted microwave and high pressure reactor
      pretreatments of cotton plant residue and its hydrolysis for fermentable sugar
      production for biofuel application.
AB  - In the present work, alkali assisted microwave pretreatment (AAMP) of cotton
      plant residue (CPR) with high pressure reactor pretreatment was compared.
      Further, modeling of AAMP was attempted. AAMP, followed by enzymatic
      saccharification was evaluated and the critical parameters were identified to be
      exposure time, particle size and enzyme loading. The levels of these parameters
      were optimized using response surface methodology (RSM) to enhance sugar yield.
      AAMP of CPR (1mm average size) for 6 min at 300 W yielded solid fractions that on
      hydrolysis resulted in maximum reducing sugar yield of 0.495 g/g. The energy
      required for AAMP at 300 W for 6 min was 108 kJ whereas high pressure
      pretreatment (180 degrees C, 100 rpm for 45 min) requires 5 times more energy
      i.e., 540 kJ. Physiochemical characterization of native and pretreated feedstock
      revealed differences between high pressure pretreatment and AAMP.

PMID- 22420988
TI  - Effect of ferric ion on nitrogen consumption, biomass and oil accumulation of a
      Scenedesmus rubescens-like microalga.
AB  - This investigation examined the effects of ferric ion source and concentration on
      the biomass yield, fatty acid methyl esters (FAME) productivity and composition
      from Scenedesmus rubescens-like microalga. The algae cultivated with Fe(2+)
      SO(4)(2-)/EDTA had higher ash free dry biomass (AFDB) production and in vivo
      chlorophyll a concentration than those with Fe(2+)-SO(4)(2-) and Fe(3+)-Cl(-)
      (P<0.001). The high or low Fe(2+) concentration can partly restrict the ammonia
      consumption, the AFDB and FAME accumulation. The algae at 1mg/L Fe(2+)
      concentration had the highest AFDB and FAME productivity (341.1 +/- 25.8 and
      107.8 +/- 19.3mg/L/d) (P<0.001). The mean content of C16 and C18 series at all
      Fe(2+) concentrations was 88.6% +/- 2.9% of total FAME, and it decreased with the
      increase of Fe(2+) concentrations. Among the fatty acids profiles, the contents
      of C18: 0, C18: 1n-7 and C18: 1n-9 are significantly changed under the different
      Fe(2+) concentrations, but not the contents of C16 series.

PMID- 22420989
TI  - 16S ribosomal DNA clone libraries to reveal bacterial diversity in anaerobic
      reactor-degraded tetrabromobisphenol A.
AB  - Microorganisms able to rapidly degrade tetrabromobisphenol A (TBBPA) were
      domesticated in an anaerobic reactor and added to gradually increased
      concentrations of TBBPA. After 240 days of domestication, the degradation rate
      reached 96.0% in cultivated batch experiments lasting 20 days. The optimum
      cultivating temperature and pH were 30 degrees C and 7.0. The bacterial
      community's composition and diversity in the reactor was studied by comparative
      analysis with 16S ribosomal DNA clone libraries. Amplified rDNA restriction
      analysis of 200 clones from the library indicate that the rDNA richness was high
      (Coverage C 99.5%) and that evenness was not high (Shannon-Weaver index 2.42).
      Phylogenetic analysis of 63 bacterial sequences from the reactor libraries
      demonstrated the presence of Betaproteobacteria (33.1%), Gammaproteobacteria
      (18.7%), Bacteroidetes (13.9%), Firmicutes (11.4%), Chloroflexi (3.6%),
      Actinobacteria (0.6%), the candidate division TM7 (4.2%) and other unknown,
      uncultured bacterial groups (14.5%). Comamonas, Achromobacter, Pseudomonas and
      Flavobacterium were the dominant types.

PMID- 22420990
TI  - Hydrogen production from sugar industry wastes using single-stage
      photofermentation.
AB  - Beet molasses and black strap are two major waste streams of the sugar industry.
      They both contain high amounts of sucrose, making them suitable substrates for
      biological hydrogen production. Photofermentation, usually used to convert
      organic acids to hydrogen, has the potential capacity to effectively use a
      variety of feed stocks, including sugars. A comparative study on
      photofermentative biohydrogen production from beet molasses, black strap, and
      sucrose was conducted. With yields of 10.5 mol H(2)/mol sucrose for beet molasses
      (1g/l sugar); 8 mol H(2)/mol sucrose for black strap (1g/l sugar) and 14 mol
      H(2)/mol sucrose for pure sucrose, a one stage photofermentation system appears
      promising as an alternative to two-stage systems given the potential savings in
      energy input and operational costs.

PMID- 22420991
TI  - Characterization of mineral paper by air-coupled ultrasonic spectroscopy.
AB  - A novel technology in the paper industry makes possible to produce paper by using
      a mineral powder and a polymer instead of cellulose fibers. This new product is
      called mineral paper, it presents some potential environmental advantages
      compared with conventional paper, while it exhibit a similar appearance and
      properties. The purpose of this work is to determine the possibilities of an air
      coupled ultrasonic technique using wide band signals and spectral analysis to
      study this kind of materials. As no direct contact nor coupling fluids between
      the paper and the transducers is required, this technique is specially well
      suited to this problem. It also offers good perspectives for the development of a
      on-line quality control system. A through transmission technique (0.15-2.3MHz) is
      employed and Fourier analysis is performed to obtain both magnitude and phase
      spectra of the transmission coefficient. Properties in the thickness direction as
      well as in the paper plane has been determined by the excitation and analysis of
      thickness and plate resonances at several incident angles and different
      directions within the paper plane. Different paper grades (from 140 to 480g/m(2))
      have been studied. Very high attenuation coefficients and very low propagation
      velocities (and hence elastic constant) have been obtained for most cases, this
      can be explained by considering the large porosity of this material (up to 50%)
      and the microstructure: a mixture of solid grains with a resin with a relatively
      large fraction of air-filled pores. Measurements show that unlike conventional
      cellulose machine made paper this material is transversely isotropic (isotropic
      in the paper plane) and that the degree of anisotropy (when in-plane directions
      are compared with the thickness direction) largely depends on the level of resin
      impregnation.

PMID- 22420992
TI  - Reduced soil water availability did not protect two competing grassland species
      from the negative effects of increasing background ozone.
AB  - Two common (semi-) natural temperate grassland species, Dactylis glomerata and
      Ranunculus acris, were grown in competition and exposed to two watering regimes:
      well-watered (WW, 20-40% v/v) and reduced-watered (RW, 7.5-20% v/v) in
      combination with eight ozone treatments ranging from pre-industrial to predicted
      2100 background levels. For both species there was a significant increase in leaf
      damage with increasing background ozone concentration. RW had no protective
      effect against increasing levels of ozone-induced senescence/injury. In high
      ozone, based on measurements of stomatal conductance, we propose that ozone
      influx into the leaves was not prevented in the RW treatment, in D. glomerata
      because stomata were a) more widely open than those in less polluted plants and
      b) were less responsive to drought. Total seasonal above ground biomass was not
      significantly altered by increased ozone; however, ozone significantly reduced
      root biomass in both species to differing amounts depending on watering regime.

PMID- 22420993
TI  - Factors affecting methylmercury biomagnification by a widespread aquatic
      invertebrate predator, the phantom midge larvae Chaoborus.
AB  - MeHg biomagnification by the phantom midge Chaoborus in relation to MeHg
      concentrations in their prey and its migratory behavior was investigated in two
      Canadian Precambrian Shield lakes. Three Chaoborus species with contrasted
      migratory behavior were collected in a fishless and a fish-inhabited lake. All
      species accumulated MeHg through their ontogenic development. In the lake
      inhabited by fish, all instars of Chaoborus punctipennis displayed a marked
      migratory behavior and were unable to biomagnify MeHg, whereas in the fishless
      lake, Chaoborus americanus and Chaoborus trivittatus biomagnified MeHg. Reduced
      biomagnification capacity of C. trivittatus, the coexisting species living with
      C. americanus, was also ascribed to a progressive vertical segregation with age.
      Growth dilution, amount and type of prey items or trophic position could not
      explain the different patterns of biomagnification. Our findings demonstrate that
      the most common invertebrate predator of temperate planktonic food webs can
      biomagnify mercury, contrarily to previous reports.

PMID- 22420995
TI  - Grip pattern and finger coordination differences between pianists and non
      pianists.
AB  - The aim of this study was to assess differences of grip pattern and finger
      coordination in pianists and non-pianists, using hand tasks that were unrelated
      to pianistic practice. Eleven pianists with more than 10 years of intensive
      practice were compared to 14 non-pianists. Both groups performed four tasks with
      their right hand: (1) gross grip at fast velocity; (2) gross grip at slow
      velocity; (3) hook grip at fast velocity; and (4) hook grip at slow velocity. The
      three-dimensional coordinates were reconstructed using a kinematic analysis
      system, and the flexion and extension angles of the metacarpophalangeal joints
      were calculated. The phase diagrams were qualitatively and quantitatively
      appraised in order to identify differences between the groups. Principal
      component analysis was used to assess differences between pianists and non
      pianists in terms of the reproducibility and regularity of palmar grip cycles.
      Coefficients of correlation between the joint angles were used to analyze finger
      coordination during the tasks. The pianists showed better reproducibility and
      regularity in the palmar grip pattern, as well as finger movements that were more
      coordinated when performing different hand tasks.

PMID- 22420994
TI  - Involvement of metabotropic glutamate receptor 5, AKT/PI3K signaling and NF
      kappaB pathway in methamphetamine-mediated increase in IL-6 and IL-8 expression
      in astrocytes.
AB  - Methamphetamine (MA) is one of the commonly used illicit drugs and the central
      nervous system toxicity of MA is well documented. The mechanisms contributing to
      this toxicity have not been fully elucidated. In this study, we investigated the
      effect of MA on the expression levels of the proinflammatory
      cytokines/chemokines, IL-6 and IL-8 in an astrocytic cell line. The IL-6 and IL-8
      RNA levels were found to increase by 4.6 +/- 0.2 fold and 3.5 +/- 0.2 fold,
      respectively, after exposure to MA for three days. Exposure of astrocytes to MA
      for 24 hours also caused increased expression of IL-6 and IL-8 at the level of
      both RNA and protein. The potential involvement of the nuclear factor-Kappa B (NF
      kappaB) pathway was explored as one of the possible mechanism(s) responsible for
      the increased induction of IL-6 and IL-8 by MA. The MA-mediated increases in IL-6
      and IL-8 were significantly abrogated by SC514. We also found that exposure of
      astrocytes to MA results in activation of NF-kappaB through the phosphorylation
      of IkappaB-alpha, followed by translocation of active NF-kappaB from the
      cytoplasm to the nucleus. In addition, treatment of cells with a specific
      inhibitor of metabotropic glutamate receptor-5 (mGluR5) revealed that MA-mediated
      expression levels of IL-6 and IL-8 were abrogated by this treatment by 42.6 +/-
      5.8% and 65.5 +/- 3.5%, respectively. Also, LY294002, an inhibitor of the
      Akt/PI3K pathway, abrogated the MA-mediated induction of IL-6 and IL-8 by 77.9 +/
      6.6% and 81.4 +/- 2.6%, respectively. Thus, our study demonstrates the
      involvement of an NF-kappaB-mediated signaling mechanism in the induction of IL-6
      and IL-8 by MA. Furthermore, we showed that blockade of mGluR5 can protect
      astrocytes from MA-mediated increases of proinflammatory cytokines/chemokines
      suggesting mGluR5 as a potential therapeutic target in treating MA-mediated
      neurotoxicity.

PMID- 22420996
TI  - Calcium deficiency increases Cd toxicity and Ca is required for heat-shock
      induced Cd tolerance in rice seedlings.
AB  - While growing in the field, plants may encounter several different forms of
      abiotic stress simultaneously, rather than a single stress. In this study, we
      investigated the effects of calcium (Ca) deficiency on cadmium (Cd) toxicity in
      rice seedlings. Calcium deficiency alone decreased the length, fresh and dry
      weight, and the Ca concentration in shoots and roots. Also, the content of
      glutathione (GSH), the ratio of GSH/oxidized glutathione, and the activity of
      catalase were lower in Ca-deficient leaves compared to control leaves. Exogenous
      Cd caused a decrease in the contents of chlorophyll and protein, and induced
      oxidative stress. Based on these stress indicators, we found that Ca deficiency
      enhanced Cd toxicity in rice seedlings. Under exogenous Cd application, internal
      Cd concentrations were higher in Ca-deficient shoots and roots than in the
      respective controls. Moreover, we observed that Ca deficiency decreased heat
      shock (HS) induced expression of HS protein genes Oshsp17.3, Oshsp17.7, and
      Oshsp18.0 in leaves thereby weakening the protection system and increasing Cd
      stress. In conclusion, Ca deficiency enhances Cd toxicity, and Ca may be required
      for HS response in rice seedlings.

PMID- 22420997
TI  - The bladder diary: do women perceive it as a useful investigation?
AB  - OBJECTIVE: The completion of a bladder diary is routinely undertaken as part of
      the initial assessment of women presenting with lower urinary tract symptoms.
      Anecdotally some women find it a nuisance to fill in a fluid volume chart. The
      QQ10 is a questionnaire which has been developed to evaluate the use of other
      questionnaires or investigations. This study aims to assess women's perception of
      completing a bladder diary as part of their investigative process and to identify
      reasons why some may fail to complete one. STUDY DESIGN: All women attending a
      one-stop urogynaecology clinic were sent instructions to fill in a three-day
      bladder diary. Those who filled a diary in were asked to fill in a QQ10
      questionnaire. Those who did not fill one in were asked to give a reason for not
      doing so. RESULTS: 128 women attended the clinic over a study period. Of these
      100 (78%) completed a diary and hence a modified QQ10 form and 28 women (22%) did
      not. The mean value score was found to be high, at 72.6 (SD 17.87) whilst the
      mean burden score was low at only 27.7 (SD. 21.14). The majority of women who did
      not fill one in claimed they had not received a diary in the first place.
      CONCLUSION: Most women appear to fill in a diary. The high mean value score and
      the low mean burden score indicate that women do not find filling in a diary a
      particularly onerous task.

PMID- 22420998
TI  - The effect of erythropoietin against oxidative damage associated with reperfusion
      following ovarian detorsion.
AB  - OBJECTIVE: To determine the effect of recombinant erythropoietin on serum
      oxidants and the viability of ischemic ovaries after detorsion. STUDY DESIGN: A
      non-randomized single-blind clinical trial was conducted from December 2009 to
      January 2011 in a University Teaching Hospital affiliated with the School of
      Medicine, Tabriz University of Medical Sciences. Surgery was carried out on 40
      patients, aged 18-35 years, with signs and symptoms of ovarian torsion. The
      patients were divided into two equal groups: group 1 received recombinant
      erythropoietin 150 IU/kg subcutaneously during the operation and 72 h after
      detorsion, and group 2 received no medication. Blood samples were taken before
      and 72 h after detorsion to determine the plasma levels of malondialdehyde,
      xanthine oxidase, glutathione, superoxide dismutase, nitric oxide, and total
      antioxidants. In both groups, the arterial and venous blood supply of the ovary
      and arterial blood flow resistance were evaluated before surgery and 72 h after
      detorsion of the ovary. The main outcome measures were improving ovarian blood
      flow and reducing oxidative damage. SPSS 17.0 was used for statistical analyses.
      RESULTS: The levels of malondialdehyde, glutathione, superoxide dismutase, nitric
      oxide, and total antioxidants 72 h after detorsion were significantly different
      between the interventional and non-interventional groups (p<0.001). There was no
      significant difference in the levels of xanthine oxidase (p=0.13). The difference
      between groups in the blood flow of the ovary 72 h after surgery was not
      statistically significant (p=0.61). CONCLUSION: Recombinant erythropoietin was
      effective in reducing the oxidative damage of ovarian torsion.

PMID- 22420999
TI  - Valsalva retinopathy secondary to hyperemesis gravidarum.

PMID- 22421000
TI  - Fluorescent organic nanoparticles self-assembled from hexa[p-(carbonyl glycin
      methyl ester) phenoxy] cyclotriphosphazene in solution.
AB  - Novel organic nanoparticles self-assembled from the hexa[p-(carbonyl glycin
      methyl ester) phenoxy] cyclotriphosphazene (HGPCP) were prepared by a simple
      solution method. The as-prepared nanoparticles were extensively characterized by
      SEM, TEM, XRD, TGA, and fluorescence spectrum. The size of nanoparticles was
      increased with increasing the HGPCP concentration in solution. The effect of
      reaction conditions on the particle size and stability was further investigated.
      Based upon the experimental results, a growth mechanism was proposed for the
      formation of the nanoparticles. The obtained nanoparticles were highly thermal
      stable and exhibited strong fluorescent emission, which could be potential
      candidates for drug-loading carriers and tracer drug delivery.

PMID- 22421002
TI  - Metastatic gastric large cell neuroendocrine carcinoma: a case report and review
      of literature.

PMID- 22421001
TI  - Oxaliplatin in combination with infusional 5-fluorouracil as first-line
      chemotherapy for elderly patients with metastatic colorectal cancer: a phase II
      study of the Spanish Cooperative Group for the Treatment of Digestive Tumors.
AB  - BACKGROUND: We previously reported a 35% overall response rate (ORR) with
      biweekly 5-fluorouracil (5-FU) continuous infusion (TTD [Spanish Cooperative
      Group for Digestive Tumour Therapy] schedule) plus irinotecan as first-line
      therapy in elderly patients with metastatic colorectal cancer (mCRC). The present
      study also was carried out in elderly patients to determine the efficacy and
      safety of the same 5-FU schedule plus oxaliplatin. PATIENTS AND METHODS: Patients
      (aged >=72 years old) with mCRC, measurable disease, ECOG (Eastern Cooperative
      Oncology Group) <=2, and no prior treatment were treated with oxaliplatin 85
      mg/m(2) plus 5-FU 3000 mg/m(2) as a 48-hour infusion every 2 weeks. RESULTS: The
      study included 134 patients, of whom, 129 were eligible. The main comorbidities
      were hypertension (44%), diabetes (17%), and chronic obstructive pulmonary
      disease (11%). The ORR and disease control rate (ORR plus stable disease) were
      52% and 80%, respectively. With a median follow-up of 14 months, the median
      progression-free survival and overall survival were 9.1 and 16.3 months,
      respectively. The most frequent grade 3/4 adverse events included neutropenia
      (16%), diarrhea (11%), and grade 3 neurotoxicity (18%). No correlation was found
      between efficacy or safety and comorbidities. CONCLUSIONS: To our knowledge, this
      is the largest phase II prospective study in elderly patients with mCRC. The
      observed efficacy and safety of this schedule compared favorably with those
      reported in this population, including regimens with monoclonal antibodies.

PMID- 22421003
TI  - Staff satisfaction between 2 models of care for the chronically critically ill.
AB  - INTRODUCTION: Chronically critically ill (CCI) patients are a growing population
      in intensive care units (ICUs), and evidence suggests that this patient group is
      perceived as demanding by healthcare professionals. However, information is
      scarce regarding organizational factors that affect staff satisfaction during the
      care of CCI patients. PURPOSE: The purpose of this study was to evaluate staff
      satisfaction between 2 models of care for the CCI. In the first model, a patient
      centered program of care in a traditional ICU was evaluated. In the second model,
      care of patients hospitalized in a multidisciplinary ICU ward dedicated to the
      CCI was further evaluated. Indicators of staff satisfaction with respect to the
      care of the CCI were also identified. METHODS: A before and after study was used
      to evaluate the 2 models of care. After implementation of the first model in
      2006, an initial evaluation was performed using a questionnaire given to ICU
      health-care personnel. In 2009, after implementing the second model (a separate
      ward for the CCI), a second evaluation took place. RESULTS: A total of 147
      participants answered the questionnaire in both phases. Participants described
      CCI as a burden, and grouping these patients into 1 ward only increased this
      perception. Overall, the staff was more satisfied with the first model of care.
      In this model, the indicators of increased satisfaction were perceived access to
      professional development and the availability of information. CONCLUSIONS:
      Results from this study provide information about health-care professionals'
      perceived burden of care when treating CCI patients. Strategies promoting
      professional development have a potential to increase staff satisfaction when it
      comes to the care of this patient group.

PMID- 22421004
TI  - Perceived benefit of a telemedicine consultative service in a highly staffed
      intensive care unit.
AB  - PURPOSE: The aim of this study was to evaluate whether a nocturnal telemedicine
      service improves culture, staff satisfaction, and perceptions of quality of care
      in a highly staffed university critical care system. METHODS: We conducted an
      experiment to determine the effect of telemedicine on nursing-staff satisfaction
      and perceptions of the quality of care in an intensive care unit (ICU). We
      surveyed ICU nurses using a modified version of a previously validated tool
      before deployment and after a 2-month experimental program of tele-ICU. Nurses in
      another, similar ICU within the same hospital academic medical center served as
      concurrent controls for the survey responses. RESULTS: Survey responses were
      measured using a 5-point Likert scale, and results were analyzed using paired t
      testing. Survey responses of the nurses in the intervention ICU (n = 27) improved
      significantly after implementation of the tele-ICU program in the relations and
      communication subscale (2.99 +/- 1.13 pre vs 3.27 +/- 1.27 post, P < .01), the
      psychological working conditions and burnout subscale (3.10 +/- 1.10 pre vs 3.23
      +/- 1.11 post, P < .02), and the education subscale (3.52 +/- 0.84 pre vs 3.76 +/
      0.78 post, P < .03). In contrast, responses in the control ICU (n = 11) declined
      in the patient care and perceived effectiveness (3.94 +/- 0.80 pre vs 3.48 +/-
      0.86 post, P < .01) and the education (3.95 +/- 0.39 pre vs 3.50 +/- 0.80 post, P
      < .05) subscales. CONCLUSION: Telemedicine has the potential to improve staff
      satisfaction and communication in highly staffed ICUs.

PMID- 22421005
TI  - Exploring the capacity to ambulate after a period of prolonged mechanical
      ventilation.
AB  - PURPOSE: The purposes were to assess the functional recovery of those who
      survived a prolonged intensive care unit (ICU) stay by reporting the proportion
      who were able to ambulate independently at hospital discharge and also to examine
      if the time duration between admission and when the patient first stood impacted
      on their capacity to ambulate at discharge. MATERIALS AND METHODS: A
      retrospective review was conducted of medical records of ICU patients in 2007 to
      2008, who were mechanically ventilated for 168 hours or more, and survived their
      acute care stay. Main outcome measures were (1) ambulation status before
      admission and at time of hospital discharge and (2) time between admission to the
      ICU and when the patient first stood. RESULTS: A total of 190 patients were
      included. Before admission, 189 (99%; 95% confidence interval [CI], 98%-100%)
      were ambulating independently, of whom 180 (95%) did not require a gait aid. On
      discharge from acute care, 89 (47%; 95% CI, 40%-54%) were ambulating
      independently, of whom 54 (61%) did not require a gait aid. Compared with those
      who stood within 30 days of ICU admission, a delay in standing of between 30 and
      60 days increased the odds 5-fold (95% CI, 2-11) of being unable to ambulate
      independently at the time of discharge. CONCLUSIONS: After a prolonged ICU
      admission, more than 50% of patients were unable to ambulate independently by
      hospital discharge, with the time between admission and first stand, being an
      important predictor of this outcome.

PMID- 22421006
TI  - The association between vital signs and major hemorrhagic injury is significantly
      improved after controlling for sources of measurement variability.
AB  - PURPOSE: Measurement error and transient variability affect vital signs. These
      issues are inconsistently considered in published reports and clinical practice.
      We investigated the association between major hemorrhagic injury and vital signs,
      successively applying analytic techniques that excluded unreliable measurements,
      reduced transient variation, and then controlled for ambiguity in individual
      vital signs through multivariate analysis. METHODS: Vital sign data from 671
      adult prehospital trauma patients were analyzed retrospectively. Computer
      algorithms were used to identify and exclude unreliable data and to apply time
      averaging. An ensemble classifier was developed and tested by cross-validation.
      Primary outcome was hemorrhagic injury plus red cell transfusion. Areas under
      receiver operating characteristic curves (ROC AUCs) were compared by the test of
      DeLong et al. RESULTS: Of initial vital signs, systolic blood pressure (BP) had
      the highest ROC AUC of 0.71 (95% confidence interval, 0.64-0.78). The ROC AUCs
      improved after excluding unreliable data, significantly for heart rate and
      respiratory rate but not significantly for BP. Time averaging to reduce temporal
      variability further increased AUCs, significantly for BP and not significantly
      for heart rate and respiratory rate. The ensemble classifier yielded a final ROC
      AUC of 0.84 (95% confidence interval, 0.80-0.89) in cross-validation.
      CONCLUSIONS: Techniques to reduce variability in vital sign data can lead to
      significantly improved diagnostic performance. Failure to consider such
      variability could significantly reduce clinical effectiveness or confound
      research investigations.

PMID- 22421007
TI  - Interim [(18)F]fluorodeoxyglucose positron emission tomography imaging in stage I
      II non-bulky Hodgkin lymphoma: would using combined positron emission tomography
      and computed tomography criteria better predict response than each test alone?
AB  - Our objective was to validate the International Harmonization Project (IHP)
      positron emission tomography (PET) response criteria and correlate with the
      Deauville criteria and diagnostic computed tomography-based (dCT) lesion size
      changes. All patients were recruited prospectively to the Cancer and Leukemia
      Group B (CALGB) 50203 trial for the treatment of stage I-II, non-bulky Hodgkin
      lymphoma (HL). [(18)F]Fluorodeoxyglucose (FDG) PET and dCT were performed at
      baseline and after two doxorubicin, vinblastine and gemcitabine (AVG) cycles (PET
      2, dCT-2) in 88 patients. IHP and Deauville criteria and percent decrease in the
      sum of the products of the perpendicular diameters (%SPPD) after two cycles were
      correlated with progression-free survival (PFS). After a median follow-up of 3.3
      years, 23.9% of patients relapsed/progressed (3-year PFS 77%). By IHP, the 2-year
      PFS was 88% and 54% for PET-2 negative and positive groups, respectively (p =
      0.0009). Similar results were obtained for Deauville criteria. In a univariate
      analysis, PET-2 predicted PFS better than %SPPD, and in a combinatorial analysis,
      in the PET-2 positive group, a negative dCT-2 increased PFS by 27-35%. However,
      some confidence intervals were large due to small sample sizes. In conclusion,
      IHP and Deauville criteria-based interpretation of PET-2 was strongly associated
      with 2-year PFS. The combined analysis of PET-2 with dCT-2 suggested a better
      predictive value for PFS compared to either test alone. Further studies are under
      way to confirm these findings.

PMID- 22421008
TI  - A comparative study of therapy duration for survivors of childhood sexual abuse.
AB  - The goal of this study was to determine whether duration of group therapy
      affected outcomes for women with a history of childhood sexual abuse (CSA). The
      sample included women from 6-month therapy groups (n = 42) and the comparison
      group who completed 12 months of therapy (n = 114). When outcomes attained by the
      6-month group were compared with those of the 12-month group, those in the 6
      month group showed significantly greater gains in self-esteem, symptom change,
      and posttraumatic stress disorder symptoms. In addition, although participants in
      the 6-month group improved more in depression scores than those in the 12-month
      group, the difference was not statistically significant. The results of this
      study indicate that intensive 6-month group therapy for female survivors of CSA
      may be even more beneficial than less intensive 12-month groups.

PMID- 22421009
TI  - Mental health considerations in pediatric enuresis.
AB  - Enuresis is a common condition during the childhood years. Although distressing
      to both children and parents, enuresis often goes unreported. Because of its
      common occurrence, psychiatric nurses should become knowledgeable about enuresis
      and understand how to assess and treat it when appropriate.

PMID- 22421010
TI  - Portraits of loneliness: emerging themes among community-dwelling older adults.
AB  - With aging comes a multitude of possible losses, including loss of health,
      spouse, friends, or independence. These losses can place older adults at risk for
      isolation and loneliness. Loneliness is of significant concern in older adults,
      as it can negatively affect their quality of life. An interpretive
      phenomenological study was conducted to explore the meaning of loneliness in 12
      older adults living in the community. Selected excerpts from the participants
      reveal several themes, as well as the importance of maintaining meaningful
      connections and relationships with others to alleviate feelings of loneliness.
      Nurses can become more attuned to the problem of loneliness in older adults and
      the importance of helping their older clients maintain meaningful connections
      with others to reduce loneliness.

PMID- 22421011
TI  - A question about the potential cardiac toxicity of escitalopram.
AB  - Previous reviews have focused on the potential cardiac toxicity of the racemic
      drug citalopram (Celexa((r))). Evaluating the safety of escitalopram
      (Lexapro((r))) is an important issue to consider, since it is the S-enantiomer of
      citalopram. Escitalopram has a small effect on the QTc interval. A prolonged QTc
      was seen in 2% to 14% of escitalopram overdose cases, without serious cardiac
      sequelae. The QTc prolongation effect of citalopram in beagle dogs has been
      attributed to the minor metabolite racemic didemethylcitalopram (DDCT). Whether
      the escitalopram minor metabolite S-DDCT has this effect is not known.
      Concentrations of S-DDCT are lower than DDCT, but for a broad range of doses of
      escitalopram and citalopram, the S-DDCT and DDCT concentrations are well below
      the QTc prolonging concentrations reported in dogs. There is no strong evidence
      from human and animal studies that the cardiac safety of escitalopram is
      significantly superior to that of citalopram.

PMID- 22421012
TI  - Human trafficking: what psychiatric nurses should know to help children and
      adolescents.
AB  - Psychiatric nurses are in key positions to identify and stop human trafficking,
      as well as aid its survivors. The combination of emotional trauma, sexual
      violence, and physical injuries experienced by these victims leads to high rates
      of posttraumatic stress disorder, depression, and anxiety. To detect human
      trafficking, it is important to identify the salient risk factors of homelessness
      and runaway history. This article offers key questions to help identify victims,
      as well as web-based resources.

PMID- 22421013
TI  - Protection of Penaeus monodon against white spot syndrome virus by inactivated
      vaccine with herbal immunostimulants.
AB  - To improve the immune response in tiger shrimp Penaeus monodon against WSSV
      infection, juveniles (350 +/- 10 mg) were vaccinated with formalin-inactivated
      WSSV and fed with herbal immunostimulants. The methanolic extracts of herbal
      immunostimulants such as Acalypha indica, Cynodon dactylon, Picrorrhiza kurrooa,
      Withania somnifera and Zingiber officinalis were incorporated in formulated diets
      at different concentrations; 250 (ED(1)), 500 (ED(2)), 1000 (ED(3)) and 2000
      (ED(4)) mg kg(-1) of feed and fed for 60 days after vaccination. After 30 and 60
      days intervals of feeding, the shrimps were challenged with WSSV, which were
      isolated and propagated from the infected crustaceans. The shrimps fed with
      control diets (C(1)) succumbed to death within 5 days after WSSV challenge, when
      no vaccination and immunostimulations were given. The other control groups (C(2)
      and C(3)) had slight improvements in all parameters including survival. The
      percentage survival was significantly (P < 0.05) increased to 30, 50 and 60% in
      the ED(2), ED(3) and ED(4) diets respectively after 60 days challenging. The
      better haematological, biochemical and immunological parameters were also found
      in the herbal extracts supplemented diets fed vaccinated shrimps. The present
      study revealed that the combined effect of immunostimulation and vaccination
      helped to boost the immune system against WSSV infection and hence this
      application can be adopted for shrimp culture.

PMID- 22421014
TI  - The function of the anterior temporal lobe: a review of the empirical evidence.
AB  - Recent work on the anterior temporal lobe (ATL) has lead to substantively
      different theoretical branches, of its putative functions, that have in some part
      developed independently of one another. The ATL has dense connectivity with a
      number of sensory modalities. This has resulted in empirical evidence that
      supports different functionality dependent upon the variables under
      investigation. The main bodies of evidence have implicated the ATL as a domain
      general semantic hub, whilst other evidence points to a domain-specific role in
      social or 'person-related' processing. A third body of evidence suggests that the
      ATLs underlie processing of unique entities. Primarily, research of the ATL has
      been based on lesion studies and from clinical populations such as semantic
      dementia or temporal lobe epilepsy patients. Although important, this
      neuropsychological evidence has a number of confounds, therefore techniques such
      as functional neuroimaging on healthy participants and the relatively novel use
      of non-invasive brain stimulation may be more useful to isolate specific
      variables that can discriminate between these different theories concerning
      'normal' function. This review focuses on these latter types of studies and
      considers the empirical evidence for each perspective. The overall literature is
      integrated in an attempt to formulate a unifying theory and the functional sub
      regions within the ATL are explored. It is concluded that a holistic integration
      of the theories is feasible in that the ATLs could process domain-general
      semantic knowledge but with a bias towards social information or stimuli that is
      personally relevant. Thus, it may be the importance of social/emotional
      information that gives it priority of processing in the ATL not an inherent
      property of the structure itself.

PMID- 22421015
TI  - Neuroinformatics analysis of molecular expression patterns and neuron populations
      in gray matter regions: the rat BST as a rich exemplar.
AB  - The rat bed nuclei of the stria terminalis (BST) is an important part of the
      cerebral nuclei, both structurally and functionally. However, the literature is
      rather scarce and more importantly, often contradictory. In this paper we review
      the literature related to neuron populations reported in different rat BST parts,
      and to a set of more than 50 expressed molecules. The information related to
      neuron populations and molecules detected in the BST was expertly collated
      manually in a publicly available neuroinformatics system, the Brain Architecture
      Knowledge Management System (BAMS; http://brancusi.usc.edu/bkms). Using the tools
      implemented in BAMS, we organized the collated information, and further analyzed
      it statistically. The result of our analysis over the set of >50 expressed
      molecules confirms the BST parcellation scheme proposed by Swanson in 2004, with
      two exceptions. We present and discuss these results, and propose refined
      parcellation ventrally in the BST. We also review and discuss the presence of
      cholinergic neurons in the BST, and of neuron populations that express serotonin
      receptors. This review is one of the most comprehensive for the rat BST published
      in the literature, and it was possible only by using neuroinformatics tools.

PMID- 22421016
TI  - Morphology of single olivocerebellar axons in the denervation-reinnervation model
      produced by subtotal lesion of the rat inferior olive.
AB  - An olivocerebellar axon branches into about seven climbing fibers (CFs) as well
      as several non-CF thin collaterals that terminate mainly in the cerebellar nuclei
      and in the granular layer. Systemic administration of 3-acetylpyridine (3-AP)
      induces degeneration of inferior olive neurons. A small number of inferior olive
      neurons survive the 3-AP treatment and grow up to make compensatory reinnervation
      on nearby Purkinje cells in their CFs. To elucidate the correlation between
      denervation-reinnervation processes and morphology of the whole axonal arbor, we
      reconstructed axonal trajectories of inferior olive neurons in the 3-AP-treated
      rat in the present study. The number of CFs per axon (average and S.D., 1.6+/
      1.1, n=11 axons) was significantly smaller in the 3-AP-treated rat than that in
      the untreated rat (about seven), indicating that inferior olive neurons that have
      a smaller number of CFs are more resistant to 3-AP neurotoxity. Predominant
      growth of CFs, as well as sprouting of thin collaterals in the cerebellar nuclei
      and in the granular layer, was observed in the 3-AP-treated rat. A CF was larger
      in size when an axon had one CF than when an axon had multiple CFs. CFs that were
      much smaller than the normal CF ("small CFs" in contrast to other "large CFs")
      were occasionally encountered at the end of thin collaterals and may be new CFs
      formed from non-CF thin collaterals. The results suggest that the capacity of
      surviving axons to reinnervate is dependent on targets and possibly limited by
      neuronal metabolism and axonal flow.

PMID- 22421017
TI  - Effects of omega-3 fish oil lipid emulsion combined with parenteral nutrition on
      patients undergoing liver transplantation.
AB  - BACKGROUND: The effect of parenteral nutrition (PN) support supplemented with
      omega-3 fatty acids was investigated in a randomized, controlled clinical trial
      at the Affiliated Drum Tower Hospital, Medical School of Nanjing University.
      MATERIALS AND METHODS: Ninety-eight patients with the diagnosis of end-stage
      liver disease or hepatic cellular carcinoma were admitted for orthotopic liver
      transplantation at the Affiliated Drum Tower Hospital. The patients were randomly
      divided into 3 groups: diet group (n = 32), PN group (n = 33), and
      polyunsaturated fatty acid (PUFA) group (n = 33). Patients in the PN and PUFA
      groups received isocaloric and isonitrogenous PN for 7 days after surgery. Venous
      heparin blood samples were obtained for assay on days 2 and 9 after surgery. A
      pathological test was performed after reperfusion of the donor liver and on day
      9. RESULTS: Alanine aminotransferase levels were improved significantly by PUFA
      treatment compared with traditional PN support (P < .05). Compared with the
      results on day 9 in the PN group, a significant difference was seen in the extent
      of increase of the prognostic nutrition index and prealbumin in the PUFA group.
      The pathological results also showed that omega-3 fatty acid supplementation
      reduced hepatic cell injury. PUFA therapy also decreased the incidence of
      infectious morbidities and shortened the posttransplant hospital stay
      significantly. CONCLUSION: Posttransplant PN support can greatly improve
      metabolism of protein and nutrition states of patients. omega-3 fatty acid
      supplemented PN significantly reduces injury of the transplanted liver, decreases
      the incidence of infectious morbidities, and shortens posttransplant hospital
      stay.

PMID- 22421018
TI  - The design and synthesis of novel, phosphonate-containing transient receptor
      potential melastatin 8 (TRPM8) antagonists.
AB  - A series of benzothiophene-based phosphonates was synthesized and many analogs
      within the series were shown to be potent antagonists of the TRPM8 channel. The
      compounds were obtained as a racemic mixture in 5 synthetic steps, and were
      tested for TRPM8 antagonist activity in a recombinant, canine TRPM8-expressing
      cell line using a fluorometric imaging plate reader (FLIPR) assay. Structure
      activity relationships were developed initially by modification of the core
      structure and subsequently by variation of the aromatic substituents and the
      phosphonate ester. Compound 9l was administered intraperitoneally to rats and
      demonstrated engagement of the TRPM8 target in both prevention and reversal-modes
      in an icilin-induced 'wet-dog' shake model.

PMID- 22421019
TI  - Discovery of S-444823, a potent CB1/CB2 dual agonist as an antipruritic agent.
AB  - The optimization of a series of 3-carbamoyl 2-pyridone derivatives as CB agonists
      is reported. These efforts resulted in the discovery of 3-(2-(1
      (cyclohexylmethyl)-2-oxo-1,2,5,6,7,8,9,10-octahydrocycloocta[b]pyridine-3
      carboxamido)thiazol-4-yl)propanoic acid (21), a potent dual CB1/CB2 agonist
      without CNS side effects induced by CB1 receptor activation. It exhibited strong
      inhibition of scratching as a 1.0% acetone solution in the pruritic model.

PMID- 22421020
TI  - Low brain penetrant CB1 receptor agonists for the treatment of neuropathic pain.
AB  - Novel, low brain penetrant, orally bioavailable CB1 receptor agonists were
      designed starting from a mature lead series of potent brain penetrant CB1
      receptor agonists. Increasing the calculated polar surface area was found to be a
      good strategy for reducing brain penetration whilst retaining drug-like
      properties. This in silico approach led to the discovery of LBP1, an orally
      bioavailable, low brain penetrant CB1 receptor agonist with robust activity in
      rodent models of neuropathic pain and a good preclinical therapeutic profile,
      which was selected for clinical development.

PMID- 22421021
TI  - Identification of novel telomeric G-quadruplex-targeting chemical scaffolds
      through screening of three NCI libraries.
AB  - Thirteen compounds with diverse chemical structures have been identified as
      selective telomeric G-quadruplex-binding ligands through screening the NCI
      Diversity Set II, the NCI Natural Products Set II and the NCI Mechanistic
      Diversity Set libraries containing a total of 2307 members against a human
      telomeric G-quadruplex using a FRET-based DNA melting assay. These compounds show
      significant selectivity towards a telomeric G-quadruplex compared to duplex DNA,
      fall within a molecular weight range of 327-533, and are generally consistent
      with the Lipinski Rule of Five for drug-likeness. Thus they provide new chemical
      scaffolds for the development of novel classes of G-quadruplex-targeting agents.

PMID- 22421022
TI  - Emergence of tularemia in the Landes area.

PMID- 22421023
TI  - Flood-associated melioidosis in a non-endemic region of Thailand.

PMID- 22421024
TI  - Cognitive impairment and dementia after intracerebral hemorrhage: a cross
      sectional study of a hospital-based series.
AB  - BACKGROUND: Frequencies of cognitive impairment and dementia have not been
      assessed in spontaneous intracerebral hemorrhage (ICH). The objective of this
      study was to determine the frequencies and patterns of cognitive impairment and
      dementia in a cross-sectional study of consecutive patients hospitalized in a
      single university medical center. METHODS: Of 183 consecutive patients
      hospitalized between 2002 and 2006, 80 survivors were contacted and 78 were
      included (mean time since stroke 40 months). Thirty patients were scored with the
      Informant Questionnaire on Cognitive Decline in the Elderly and Instrumental
      Activities of Daily Living in a telephone interview, and 48 underwent a
      comprehensive clinical and neuropsychological assessment. RESULTS: Dementia was
      observed in 18 of 78 patients (23%; 95% confidence interval [CI] 13-32%) and
      cognitive impairment without dementia was seen in 37 of 48 patients (77%; 95% CI
      65-89%). The cognitive disorders mainly concerned episodic memory (52%),
      psychomotor speed (44%), and executive function (37%), followed by language and
      visuoconstructive abilities. In a logistic regression analysis, Rankin score >1
      at discharge and hemorrhage volume were the initial factors to be selected as a
      predictor of long-term dementia. CONCLUSIONS: This single-center, cross-sectional
      study revealed that the prevalence of dementia and cognitive impairment without
      dementia after ICH are high and are similar to those observed in cerebral
      infarct. Further longitudinal, prospective studies are required to assess
      accurately the prevalence, mechanisms and predictors of post-ICH dementia.

PMID- 22421025
TI  - Lateral patterning of multilayer InAs/GaAs(001) quantum dot structures by in
      vacuo focused ion beam.
AB  - We report on the effects of patterning and layering on multilayer InAs/GaAs(001)
      quantum dot structures laterally ordered using an in vacuo focused ion beam. The
      patterned hole size and lateral pattern spacing affected the quantum dot size and
      the fidelity of the quantum dots with respect to the lateral patterns. 100%
      pattern fidelity was retained after six layers of dots for a 9.0 ms focused ion
      beam dwell time and 2.0 um lateral pattern spacing. Analysis of the change in
      quantum dot size as a function of pattern spacing provided a means of estimating
      the maximum average adatom surface diffusion length to be approximately 500 nm,
      and demonstrated the ability to alter the wetting layer thickness via pattern
      spacing. Increasing the number of layers from six to 26 resulted in mound
      formation, which destroyed the pattern fidelity at close pattern spacings and led
      to a bimodal quantum dot size distribution as measured by atomic force
      microscopy. The bimodal size distribution also affected the optical properties of
      the dots, causing a split quantum dot photoluminescence peak where the separation
      between the split peaks increased with increasing pattern spacing.

PMID- 22421026
TI  - Cr(VI) adsorption from electroplating plating wastewater by chemically modified
      coir pith.
AB  - Coir pith samples were chemically modified by grafting with acrylic acid for the
      removal of Cr(VI) from electroplating wastewater. The presence of acrylic acid on
      the coir pith surface was verified by a scanning electron microscope with an
      electron dispersive x-ray spectrometer (SEM/EDX), Fourier transform infrared
      spectroscopy (FTIR) and thermogravimetry (TG). The carbonyl groups (C==O) from
      the carboxylic acids (COOH) increased on the coir pith surface after grafting
      with acrylic acid. In addition, the thermal stability of the acrylic acid-grafted
      coir pith also improved. The optimum conditions for grafting the acrylic acid on
      the coir pith consisted of 2 M acrylic acid and 0.00125 M ceric ammonium nitrate
      (CAN, as an initiator). The maximum Cr(VI) removal (99.99 +/- 0.07%) was obtained
      with the following conditions: a 1.3% (w/v) dosage of acrylic acid-grafted coir
      pith, a system pH of 2, a contact time of 22 h, a temperature of 30  degrees C, a
      particle size of <150 MUm and an initial Cr(VI) of 1,171 mg l(-1). At system pH
      of 2, Cr(VI) in the HCrO(4)(-) form can be adsorbed with acrylic acid-grafted
      coir pith via an electrostatic attraction. The adsorption isotherm of 2 M acrylic
      acid-grafted coir pith exhibited a good fit with the Langmuir isotherm. The
      maximum Cr(VI) adsorption capacity of the 2 M acrylic acid-grafted coir pith was
      196.00 mg Cr(VI) g(-1) adsorbent, whereas for coir pith without grafting, the
      maximum Cr(VI) removal was 165.00 mg Cr(VI) g(-1) adsorbent. The adsorption
      capacity of the acrylic acid-grafted coir pith for Cr(VI) was higher compared to
      the original coir pith. This result was due to the enhancement of the carbonyl
      groups on the coir pith surface that may have involved the mechanism of chromium
      adsorption. The X-ray absorption near edged structure (XANES) and desorption
      studies suggested that most of the Cr(III) that presented on the acrylic acid
      grafted coir pith was due to the Cr(VI) being reduced to Cr(III) on the adsorbent
      surface. FTIR confirmed the involvement of the carbonyl groups (C==O) and the
      methoxy groups (OCH3) in the mechanism of chromium adsorption. Thermodynamic
      study, such as enthalpy (DeltaH), free energy (DeltaG) and entropy change
      (DeltaS) indicated that the overall adsorption process was endothermic,
      spontaneous and randomness. In addition, the adsorption process was favored at
      high temperatures.

PMID- 22421027
TI  - Two-dimensional strain rate and Doppler tissue myocardial velocities: analysis by
      echocardiography of hemodynamic and functional changes of the failed left
      ventricle during different degrees of extracorporeal life support.
AB  - BACKGROUND: To evaluate hemodynamic and functional changes of the failed left
      ventricle by Velocity Vector Imaging (VVI) and tissue Doppler, 22 patients with
      cardiogenic shock supported by extracorporeal life support (ECLS) were imaged
      during ECLS output variations inducing severe load manipulations. METHODS: The
      following data were acquired: (1) mean arterial pressure, aortic Doppler velocity
      time integral, left ventricular end-diastolic volume, and mitral Doppler E wave;
      (2) tissue Doppler systolic (Sa) and early diastolic (Ea) velocities; and (3)
      systolic peak velocity (Sv), strain, and strain rate using VVI. RESULTS: Load
      variations were documented by a significant decrease in afterload (mean arterial
      pressure, -21%), an increase in preload (left ventricular end-diastolic volume,
      +12%; E, +46%; E/Ea ratio, +22%), and an increase in the velocity-time integral
      (+45%). VVI parameters increased (Sv, +36%; strain, +81%; and strain rate, +67%;
      P < .05), unlike tissue Doppler systolic velocities (+2%; P = NS). Whatever the
      ECLS flow, Sa was higher in patients who survived. CONCLUSIONS: VVI parameters
      are not useful in characterizing the failed left ventricle with rapidly varying
      load conditions. Tissue Doppler systolic velocities appear to be load independent
      and thus could help in the management of ECLS patients.

PMID- 22421028
TI  - Risk assessment of ventricular arrhythmias in patients with nonischemic dilated
      cardiomyopathy by strain echocardiography.
AB  - BACKGROUND: Indications for prophylactic implantable cardioverter-defibrillator
      implantation in patients with nonischemic dilated cardiomyopathy (DCM) are based
      on left ventricular (LV) ejection fraction (LVEF), although LVEF has limited
      ability to predict arrhythmias. It has recently been shown that strain
      echocardiography can predict ventricular arrhythmias in patients after myocardial
      infarction. The aim of this study was to evaluate whether strain echocardiography
      may help in the risk stratification of ventricular arrhythmias in patients with
      DCM. METHODS: Ninety-four patients with nonischemic DCM were prospectively
      included. By speckle-tracking strain echocardiography, global longitudinal strain
      was calculated as the average of peak longitudinal strain from a 16-segment LV
      model. The time interval from electrocardiographic peak R to peak negative strain
      was assessed in each LV segment. Mechanical dispersion was defined as the
      standard deviation of time to peak negative strain from 16 LV segments. RESULTS:
      After a median of 22 months of follow-up (range, 1-46 months), 12 patients (13%)
      had experienced arrhythmic events, defined as sustained ventricular tachycardia
      or cardiac arrest. LVEF and global longitudinal strain were reduced in patients
      with DCM with arrhythmic events compared with those without (28 +/- 10% vs 38 +/-
      13%, P = .01, and -6.4 +/- 3.3% vs -12.3 +/- 5.2%, P < .001, respectively).
      Global longitudinal strain showed greater area under the curve than LVEF to
      identify arrhythmic events in receiver operating characteristic curve analyses (P
      = .05). Patients with arrhythmic events had increased mechanical dispersion (98
      +/- 43 vs 56 +/- 18 ms, P < .001). Mechanical dispersion predicted arrhythmias
      independently of LVEF (hazard ratio, 1.28; 95% confidence interval, 1.11-1.49; P
      = .001). CONCLUSIONS: Global longitudinal strain is a promising marker of
      arrhythmias. Mechanical dispersion predicted arrhythmic events in patients with
      DCM independently of LVEF. Strain echocardiography may help in the risk
      stratification of patients with DCM not fulfilling current implantable
      cardioverter-defibrillator indications.

PMID- 22421029
TI  - Serial assessment of right ventricular volume and function in surgically
      palliated hypoplastic left heart syndrome using real-time transthoracic three
      dimensional echocardiography.
AB  - BACKGROUND: Right ventricular (RV) failure is a major cause of morbidity and
      mortality in patients with hypoplastic left heart syndrome (HLHS), but the
      longitudinal course of RV volumes through staged palliation (SP) has not been
      previously investigated. The aim of this study was to evaluate RV volume and
      function longitudinally through SP of HLHS using real-time three-dimensional
      echocardiography. METHODS: A total of 18 subjects with HLHS were prospectively
      studied at four time points from diagnosis through stage 2 (SP2). Real-time three
      dimensional echocardiographic full-volume data sets were acquired in high-frame
      rate mode with electrocardiographic gating. Volumetric and functional analyses
      were performed using a semiautomatic contour detection algorithm. Eighteen age
      matched and sex-matched normal infants (aged 0-6 months) were studied at
      comparable time points as controls. RESULTS: Presurgical examinations (pre-stage
      1 [SP1]; n = 18) were performed at a mean age of 4 days, post-SP1 examinations (n
      = 17) at a mean age of 20 days, pre-SP2 examinations (n = 14) at a mean age of
      4.6 months, and post-SP2 examinations (n = 14) at a mean age of 5.5 months,
      constituting a total of 63 examinations. The mean values of RV end-diastolic
      volume indexed to body surface area (EDVi) at the four time points were 87 +/-
      30, 104 +/- 39, 112 +/- 34, and 102 +/- 35 mL/m(2), respectively. There was an
      increase in EDVi (P = .024) from pre-SP1 to post-SP1 but no significant change
      between post-SP1 and pre-SP2. The decrease in EDVi after SP2 did not reach
      statistical significance. Mean RV ejection fractions (EFs) were 50 +/- 5%, 45 +/-
      5%, 46 +/- 5%, and 38 +/- 4%, respectively. There was a trend toward decreasing
      EF throughout SP, with statistically significant decreases from pre-SP1 to post
      SP1 (P = .003) and from pre-SP2 to post-SP2 (P < .001). In normal infants, the
      mean RV EDVi was 50 +/- 10 mL/m(2) (approximately half that of patients with
      HLHS), and the mean EF was 51 +/- 3%. There was good interobserver agreement for
      EDVi, end-systolic volume indexed to body surface area, and EF. CONCLUSIONS: Real
      time three-dimensional echocardiography is a reproducible means for evaluating RV
      volumes and EFs in patients with HLHS. Indexed RV diastolic volume remains stable
      to slightly increased, and RV EF deteriorates as the first two stages of surgical
      palliation are accomplished. The findings of this study highlight the adverse
      physiology of HLHS, which deteriorates even among early survivors despite SP.

PMID- 22421030
TI  - A hierarchy of distress and invariant item ordering in the General Health
      Questionnaire-12.
AB  - BACKGROUND: Invariant item ordering (IIO) is defined as the extent to which items
      have the same ordering (in terms of item difficulty/severity - i.e. demonstrating
      whether items are difficult [rare] or less difficult [common]) for each
      respondent who completes a scale. IIO is therefore crucial for establishing a
      scale hierarchy that is replicable across samples, but no research has
      demonstrated IIO in scales of psychological distress. We aimed to determine if a
      hierarchy of distress with IIO exists in a large general population sample who
      completed a scale measuring distress. METHODS: Data from 4107 participants who
      completed the 12-item General Health Questionnaire (GHQ-12) from the Northern
      Ireland Health and Social Wellbeing Survey 2005-6 were analysed. Mokken scaling
      was used to determine the dimensionality and hierarchy of the GHQ-12, and items
      were investigated for IIO. RESULTS: All items of the GHQ-12 formed a single,
      strong unidimensional scale (H=0.58). IIO was found for six of the 12 items (H
      trans=0.55), and these symptoms reflected the following hierarchy: anhedonia,
      concentration, participation, coping, decision-making and worthlessness.
      LIMITATIONS: The cross-sectional analysis needs replication. CONCLUSIONS: The GHQ
      12 showed a hierarchy of distress, but IIO is only demonstrated for six of the
      items, and the scale could therefore be shortened. Adopting brief, hierarchical
      scales with IIO may be beneficial in both clinical and research contexts.

PMID- 22421031
TI  - The effect of lithium ions on the hydrophobic effect: does lithium affect
      hydrophobicity differently than other ions?
AB  - Ionic species have been shown to significantly perturb the interactions between
      non-polar solutes in aqueous solution. These perturbations are often analyzed in
      terms of the interactions existing between hydrophobic surfaces and ions. It has
      been known for some time, that ions with a high charge density are repelled from
      hydrophobic surfaces while ions with a low charge density tend to stick to these
      surfaces. Therefore, from a continuum model standpoint, small monovalent ions
      promote hydrophobicity by minimizing the exposed hydrophobic surface area, while
      "sticky" large monovalent ions interact with the hydrophobic surfaces and
      discourage aggregation. However, the charge-dense lithium ion often exhibits
      anomalous behaviour different from these predicted trends: instead of enhancing,
      the addition of lithium ions often seems to weaken the hydrophobic effect and on
      the contrary help dissolve hydrophobic molecules. This weakening of apparent
      hydrophobicity is considered to be one of the reasons for the protein denaturing
      properties of lithium salts. Recent theoretical and experimental results however
      have shown that lithium cations can interact with a variety of molecular
      functional groups. This suggests that this apparent lithium-induced lowering of
      hydrophobicity, that is often reported in the literature may be a result of
      specific interactions between these molecular functional groups and lithium,
      rather than weakening the interaction between hydrophobic surfaces. This work
      examines these possibilities by studying the effect of various cations on the
      simple hydrophobic interaction existing between methyl and phenyl contact-pairs
      and demonstrates that the effect of lithium cations on the hydrophobic effect
      follows the trend predicted by continuum models. In other words, the influence of
      an ion on the hydrophobic interaction between two non-polar surfaces is a
      function of the interaction of that ion and each non-polar surface.

PMID- 22421032
TI  - Removal of MS2, Qbeta and GA bacteriophages during drinking water treatment at
      pilot scale.
AB  - The removal of MS2, Qbeta and GA, F-specific RNA bacteriophages, potential
      surrogates for pathogenic waterborne viruses, was investigated during a
      conventional drinking water treatment at pilot scale by using river water,
      artificially and independently spiked with these bacteriophages. The objective of
      this work is to develop a standard system for assessing the effectiveness of
      drinking water plants with respect to the removal of MS2, Qbeta and GA
      bacteriophages by a conventional pre-treatment process (coagulation-flocculation
      settling-sand filtration) followed or not by an ultrafiltration (UF) membrane
      (complete treatment process). The specific performances of three UF membranes
      alone were assessed by using (i) pre-treated water and (ii) 0.1 mM sterile
      phosphate buffer solution (PBS), spiked with bacteriophages. These UF membranes
      tested in this work were designed for drinking water treatment market and were
      also selected for research purpose. The hypothesis serving as base for this study
      was that the interfacial properties for these three bacteriophages, in terms of
      electrostatic charge and the degree of hydrophobicity, could induce variations in
      the removal performances achieved by drinking water treatments. The comparison of
      the results showed a similar behaviour for both MS2 and Qbeta surrogates whereas
      it was particularly atypical for the GA surrogate. The infectious character of
      MS2 and Qbeta bacteriophages was mostly removed after clarification followed by
      sand filtration processes (more than a 4.8-log reduction) while genomic copies
      were removed at more than a 4.0-log after the complete treatment process. On the
      contrary, GA bacteriophage was only slightly removed by clarification followed by
      sand filtration, with less than 1.7-log and 1.2-log reduction, respectively.
      After the complete treatment process achieved, GA bacteriophage was removed with
      less than 2.2-log and 1.6-log reduction, respectively. The effectiveness of the
      three UF membranes tested in terms of bacteriophages removal showed significant
      differences, especially for GA bacteriophage. These results could provide
      recommendations for drinking water suppliers in terms of selection criteria for
      membranes. MS2 bacteriophage is widely used as a surrogate for pathogenic
      waterborne viruses in Europe and the United States. In this study, the choice of
      MS2 bacteriophage as the best surrogate to be used for assessment of the
      effectiveness of drinking water treatment in removal of pathogenic waterborne
      viruses in worst conditions is clearly challenged. It was shown that GA
      bacteriophage is potentially a better surrogate as a worst case than MS2.
      Considering GA bacteriophage as the best surrogate in this study, a chlorine
      disinfection step could guaranteed a complete removal of this model and ensure
      the safety character of drinking water plants.

PMID- 22421033
TI  - [Recurrent unilateral optic neuropathy associated with human immunodeficiency
      virus (HIV)].
AB  - HIV-related optic neuropathy is rare compared to optic neuropathies secondary to
      opportunistic infections in seropositive patients. We report the case of a 39
      year-old HIV-positive woman referred for unilateral visual loss leading to the
      diagnosis of recurrent, unilateral, inflammatory optic neuropathy directly
      associated with HIV. Despite initial recovery after steroid treatment, she
      relapsed twice. Absence of any opportunist infections or toxic causes and
      presence of a very high viral load due to non-compliance with treatment led to
      the diagnosis of HIV-related optic neuropathy. Steroids and effective anti
      retroviral treatment resulted in definitive and complete recovery. Inflammatory,
      degenerative and/or vascular mechanisms have been hypothesized to explain the
      occurrence of these rare HIV-related optic neuropathies. This diagnosis remains a
      diagnosis of exclusion to be considered in the work-up of seropositive patients
      with optic neuropathies.

PMID- 22421034
TI  - [Binocular movements during pursuit and reading: eye tracking study].
AB  - Detailed analysis of fine, slow ocular movements has not been the object of
      recent studies. With this in mind, special hardware and a simple testing protocol
      were developed, along with software for recording and analysis. The study of
      these movements, using this hardware adapted to follow both eyes, allowed the
      inclusion of binocularity in the precise analysis of ocular pursuit and reading.
      Recording the eye movements of 166 children and adults permitted identification
      of the main features of oculomotor development from age five years. These
      movements were studied during calibrated pursuit and reading. The persistence of
      oculomotor abnormalities during development can help to define an array of
      "visual immaturity" or "visual inefficiency". The study of these anomalies during
      reading explains some learning difficulties.

PMID- 22421035
TI  - [Retroperitoneal haemorrhage after traumatic rupture of a phaechromocytoma].

PMID- 22421036
TI  - Eliminating mitochondrial DNA from sperm.
AB  - Most eukaryotes show uniparental inheritance of mitochondrial DNA (mtDNA). In
      this issue of Developmental Cell, DeLuca and O'Farrell (2012) show that active
      elimination of mtDNA during sperm development in Drosophila ensures that mature
      spermatozoa are devoid of DNA.

PMID- 22421037
TI  - GEFs on the RhoAd to a colossal nucleus.
AB  - Cytokinesis in normal cell division requires RhoA-regulated actomyosin
      contraction of the cleavage furrow; this process is aborted in megakaryocyte
      endomitosis, leading to polyploidy. In this issue of Developmental Cell, Gao et
      al. (2012) trace the basis of endomitosis to sequential downregulation of guanine
      nucleotide exchange factors GEF-H1 and ECT2.

PMID- 22421038
TI  - A local view of cancer.
AB  - Research on solid tumors has had limited emphasis on interactions between
      transformed cells and their neighbors within the epithelium. Leung and Brugge
      (2012) use cultured breast cancer acini to demonstrate the importance of local
      interactions between normal and transformed epithelial cells, with important
      implications for our understanding of epithelial cancers.

PMID- 22421039
TI  - The inner compass of spindle positioning and orientation.
AB  - Polarized cortical cues are known to guide spindle movements to dictate division
      axis and cleavage site during asymmetric cell division. In a recent issue of
      Nature Cell Biology, Kiyomitsu and Cheeseman (2012) report two novel spindle
      intrinsic signals that regulate spindle orientation and position in symmetrically
      dividing human cells.

PMID- 22421040
TI  - (Re)inventing the circadian feedback loop.
AB  - For 20 years, researchers have thought that circadian clocks are defined by
      feedback loops of transcription and translation. The rediscovery of
      posttranslational circadian oscillators in diverse organisms forces us to rethink
      this paradigm. Meanwhile, the original "basic" feedback loops of canonical
      circadian clocks have swelled to include dozens of additional proteins acting in
      interlocked loops. We review several self-sustained clock mechanisms and propose
      that minimum requirements for diurnal timekeeping might be simpler than those of
      actual free-running circadian oscillators. Thus, complex mechanisms of circadian
      timekeeping might have evolved from random connections between unrelated feedback
      loops with independent but limited time-telling capability.

PMID- 22421042
TI  - In vivo imaging of molecular interactions at damaged sarcolemma.
AB  - Muscle cells have a remarkable capability to repair plasma membrane lesions.
      Mutations in dysferlin (dysf) are known to elicit a progressive myopathy in
      humans, probably due to impaired sarcolemmal repair. We show here that loss of
      Dysf and annexin A6 (Anxa6) function lead to myopathy in zebrafish. By use of
      high-resolution imaging of myofibers in intact animals, we reveal sequential
      phases in sarcolemmal repair. Initially, membrane vesicles enriched in Dysf
      together with cytoplasmic Anxa6 form a tight patch at the lesion independently of
      one another. In the subsequent steps, annexin A2a (Anxa2a) followed by annexin
      A1a (Anxa1a) accumulate at the patch; the recruitment of these annexins depends
      on Dysf and Anxa6. Thus, sarcolemmal repair relies on the ordered assembly of a
      protein-membrane scaffold. Moreover, we provide several lines of evidence that
      the membrane for sarcolemmal repair is derived from a specialized plasma membrane
      compartment.

PMID- 22421041
TI  - ALK1 signaling inhibits angiogenesis by cooperating with the Notch pathway.
AB  - Activin receptor-like kinase 1 (ALK1) is an endothelial-specific member of the
      TGF-beta/BMP receptor family that is inactivated in patients with hereditary
      hemorrhagic telangiectasia (HHT). How ALK1 signaling regulates angiogenesis
      remains incompletely understood. Here we show that ALK1 inhibits angiogenesis by
      cooperating with the Notch pathway. Blocking Alk1 signaling during postnatal
      development in mice leads to retinal hypervascularization and the appearance of
      arteriovenous malformations (AVMs). Combined blockade of Alk1 and Notch signaling
      further exacerbates hypervascularization, whereas activation of Alk1 by its high
      affinity ligand BMP9 rescues hypersprouting induced by Notch inhibition.
      Mechanistically, ALK1-dependent SMAD signaling synergizes with activated Notch in
      stalk cells to induce expression of the Notch targets HEY1 and HEY2, thereby
      repressing VEGF signaling, tip cell formation, and endothelial sprouting. Taken
      together, these results uncover a direct link between ALK1 and Notch signaling
      during vascular morphogenesis that may be relevant to the pathogenesis of HHT
      vascular lesions.

PMID- 22421043
TI  - ADF/cofilin regulates actomyosin assembly through competitive inhibition of
      myosin II binding to F-actin.
AB  - The contractile actin cortex is important for diverse fundamental cell processes,
      but little is known about how the assembly of F-actin and myosin II motors is
      regulated. We report that depletion of actin depolymerizing factor (ADF)/cofilin
      proteins in human cells causes increased contractile cortical actomyosin
      assembly. Remarkably, our data reveal that the major cellular defects resulting
      from ADF/cofilin depletion, including cortical F-actin accumulation, were largely
      due to excessive myosin II activity. We identify that ADF/cofilins from
      unicellular organisms to humans share a conserved activity to inhibit myosin II
      binding to F-actin, indicating a mechanistic rationale for our cellular results.
      Our study establishes an essential requirement for ADF/cofilin proteins in the
      control of normal cortical contractility and in processes such as mitotic
      karyokinesis. We propose that ADF/cofilin proteins are necessary for controlling
      actomyosin assembly and intracellular contractile force generation, a function of
      equal physiological importance to their established roles in mediating F-actin
      turnover.

PMID- 22421044
TI  - Disruption of SoxB1-dependent Sonic hedgehog expression in the hypothalamus
      causes septo-optic dysplasia.
AB  - Septo-optic dysplasia (SOD) is a congenital brain anomaly that results in
      pituitary, optic nerve, and midline forebrain defects. The etiology of SOD is
      poorly understood, with the majority of cases being sporadic. In rare instances,
      SOD is caused by mutations in Sox2, Sox3, or Hesx1, but how this manifests in
      disease is not entirely certain. We demonstrate here that mouse embryos lacking
      Sonic hedgehog (Shh) in the prospective hypothalamus exhibit key features of SOD,
      including pituitary hypoplasia and absence of the optic disc. The hypothalamic
      source of Shh is required to maintain gene expression boundaries along the
      anteroposterior and mediolateral neural axes that are important for proper
      pituitary and eye development, respectively. We further reveal that Sox2 and Sox3
      are dose-dependent regulators of Shh transcription that directly bind and
      activate a long-range Shh forebrain enhancer. These data indicate that reduced
      levels of Shh expression in the hypothalamus cause SOD.

PMID- 22421045
TI  - Sox9 directs hypertrophic maturation and blocks osteoblast differentiation of
      growth plate chondrocytes.
AB  - The transcription factor Sox9 is necessary for early chondrogenesis, but its
      subsequent roles in the cartilage growth plate, a highly specialized structure
      that drives skeletal growth and endochondral ossification, remain unclear. Using
      a doxycycline-inducible Cre transgene and Sox9 conditional null alleles in the
      mouse, we show that Sox9 is required to maintain chondrocyte columnar
      proliferation and generate cell hypertrophy, two key features of functional
      growth plates. Sox9 keeps Runx2 expression and beta-catenin signaling in check
      and thereby inhibits not only progression from proliferation to prehypertrophy,
      but also subsequent acquisition of an osteoblastic phenotype. Sox9 protein
      outlives Sox9 RNA in upper hypertrophic chondrocytes, where it contributes with
      Mef2c to directly activate the major marker of these cells, Col10a1. These
      findings thus reveal that Sox9 remains a central determinant of the lineage fate
      and multistep differentiation program of growth plate chondrocytes and thereby
      illuminate our understanding of key molecular mechanisms underlying
      skeletogenesis.

PMID- 22421046
TI  - The MOF chromobarrel domain controls genome-wide H4K16 acetylation and spreading
      of the MSL complex.
AB  - The histone H4 lysine 16 (H4K16)-specific acetyltransferase MOF is part of two
      distinct complexes involved in X chromosome dosage compensation and autosomal
      transcription regulation. Here we show that the MOF chromobarrel domain is
      essential for H4K16 acetylation throughout the Drosophila genome and is required
      for spreading of the male-specific lethal (MSL) complex on the X chromosome. The
      MOF chromobarrel domain directly interacts with nucleic acids and potentiates
      MOF's enzymatic activity after chromatin binding, making it a unique example of a
      chromo-like domain directly controlling acetylation activity in vivo. We also
      show that the Drosophila-specific N terminus of MOF has evolved to perform sex
      specific functions. It modulates nucleosome binding and HAT activity and controls
      MSL complex assembly, thus regulating MOF function in dosage compensation. We
      propose that MOF has been especially tailored to achieve tight regulation of its
      enzymatic activity and enable its dual role on X and autosomes.

PMID- 22421047
TI  - Nanog-like regulates endoderm formation through the Mxtx2-Nodal pathway.
AB  - In mammalian embryonic stem cells, the acquisition of pluripotency is dependent
      on Nanog, but the in vivo analysis of Nanog has been hampered by its requirement
      for early mouse development. In an effort to examine the role of Nanog in vivo,
      we identified a zebrafish Nanog ortholog and found that its knockdown impaired
      endoderm formation. Genome-wide transcription analysis revealed that nanog-like
      morphants fail to develop the extraembryonic yolk syncytial layer (YSL), which
      produces Nodal, required for endoderm induction. We examined the genes that were
      regulated by Nanog-like and identified the homeobox gene mxtx2, which is both
      necessary and sufficient for YSL induction. Chromatin immunoprecipitation assays
      and genetic studies indicated that Nanog-like directly activates mxtx2, which, in
      turn, specifies the YSL lineage by directly activating YSL genes. Our study
      identifies a Nanog-like-Mxtx2-Nodal pathway and establishes a role for Nanog-like
      in regulating the formation of the extraembryonic tissue required for endoderm
      induction.

PMID- 22421048
TI  - Distinct compartments of the proepicardial organ give rise to coronary vascular
      endothelial cells.
AB  - The proepicardial organ is an important transient structure that contributes
      cells to various cardiac lineages. However, its contribution to the coronary
      endothelium has been disputed, with conflicting data arising in chick and mouse.
      Here we resolve this conflict by identifying two proepicardial markers, Scleraxis
      (Scx) and Semaphorin3D (Sema3D), that genetically delineate heretofore
      uncharacterized proepicardial subcompartments. In contrast to previously fate
      mapped Tbx18/WT-1-expressing cells that give rise to vascular smooth muscle, Scx-
      and Sema3D-expressing proepicardial cells give rise to coronary vascular
      endothelium both in vivo and in vitro. Furthermore, Sema3D(+) and Scx(+)
      proepicardial cells contribute to the early sinus venosus and cardiac
      endocardium, respectively, two tissues linked to vascular endothelial formation
      at later stages. Taken together, our studies demonstrate that the proepicardial
      organ is a molecularly compartmentalized structure, reconciling prior chick and
      mouse data and providing a more complete understanding of the progenitor
      populations that establish the coronary vascular endothelium.

PMID- 22421049
TI  - Barriers to male transmission of mitochondrial DNA in sperm development.
AB  - Across the eukaryotic phylogeny, offspring usually inherit their mitochondrial
      genome from only one of two parents: in animals, the female. Although mechanisms
      that eliminate paternally derived mitochondria from the zygote have been sought,
      the developmental stage at which paternal transmission of mitochondrial DNA is
      restricted is unknown in most animals. Here, we show that the mitochondria of
      mature Drosophila sperm lack DNA, and we uncover two processes that eliminate
      mitochondrial DNA during spermatogenesis. Visualization of mitochondrial DNA
      nucleoids revealed their abrupt disappearance from developing spermatids in a
      process requiring the mitochondrial nuclease, Endonuclease G. In Endonuclease G
      mutants, persisting nucleoids are swept out of spermatids by a cellular
      remodeling process that trims and shapes spermatid tails. Our results show that
      mitochondrial DNA is eliminated during spermatogenesis, thereby removing the
      capacity of sperm to transmit the mitochondrial genome to the next generation.

PMID- 22421050
TI  - GOLVEN secretory peptides regulate auxin carrier turnover during plant
      gravitropic responses.
AB  - Growth and development are coordinated by an array of intercellular
      communications. Known plant signaling molecules include phytohormones and hormone
      peptides. Although both classes can be implicated in the same developmental
      processes, little is known about the interplay between phytohormone action and
      peptide signaling within the cellular microenvironment. We show that genes coding
      for small secretory peptides, designated GOLVEN (GLV), modulate the distribution
      of the phytohormone auxin. The deregulation of the GLV function impairs the
      formation of auxin gradients and alters the reorientation of shoots and roots
      after a gravity stimulus. Specifically, the GLV signal modulates the trafficking
      dynamics of the auxin efflux carrier PIN-FORMED2 involved in root tropic
      responses and meristem organization. Our work links the local action of secretory
      peptides with phytohormone transport.

PMID- 22421051
TI  - Seeing patterns through the hemodynamic veil--the future of pattern-information
      fMRI.
AB  - Pattern-information fMRI (pi-fMRI) has become a popular method in neuroscience.
      The technique is motivated by the idea that spatial patterns of fMRI activity
      reflect the neuronal population codes of perception, cognition, and action. In
      this commentary, we discuss three fundamental outstanding questions: (1) What is
      the relationship between neuronal patterns and fMRI patterns? (2) Does pattern
      information fMRI benefit from hyperacuity, enabling the investigation of columnar
      level neuronal information, even at low resolution? (3) Do high-resolution and
      high-field fMRI increase sensitivity to pattern information? The empirical
      answers will enable us to optimize pi-fMRI data acquisition and to understand the
      ultimate potential and appropriate interpretation of pi-fMRI results.
      Furthermore, considering the relationship between neuronal activity and fMRI at
      the level of spatiotemporal patterns provides a novel and important perspective
      on the basis of the fMRI signal.

PMID- 22421052
TI  - The future of acquisition speed, coverage, sensitivity, and resolution.
AB  - Two decades of technology development has continually improved the image quality,
      spatial-temporal resolution, and sensitivity of the fMRI acquisition. In this
      article, I assess our current acquisition needs, briefly examine the
      technological breakthroughs that have benefited fMRI in the past, and look at
      some promising technologies that are currently under development to try to
      envision what the fMRI acquisition protocol of the future might look like.

PMID- 22421053
TI  - Television advertising and branding. Effects on eating behaviour and food
      preferences in children.
AB  - Television provides one of the first, and most intimate, experiences of
      commercial food promotion. Therefore, unsurprisingly, the effects of television
      advertising on children's brand preferences are well established. However, its
      effect on actual food intake and the food choices in children of various weight
      statuses has only recently been characterised. Despite regulation, children in
      the UK are exposed to considerable numbers of food adverts on television. These
      are predominantly for foods high in fat, salt and sugar (HFSS), which are
      marketed to children using promotional characters and themes of fun. Such adverts
      have been shown to cause significant increases in intake, particularly in
      overweight and obese children, and enhanced preference for high carbohydrate and
      high fat foods in children who consume the greatest amounts of televisual media.

PMID- 22421055
TI  - Commentary: a step towards more comprehensive analyses of life course effects of
      mixtures of environmental factors.

PMID- 22421054
TI  - Systematic evaluation of environmental factors: persistent pollutants and
      nutrients correlated with serum lipid levels.
AB  - BACKGROUND: Both genetic and environmental factors contribute to triglyceride,
      low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein
      cholesterol (HDL-C) levels. Although genome-wide association studies are
      currently testing the genetic factors systematically, testing and reporting one
      or a few factors at a time can lead to fragmented literature for environmental
      chemical factors. We screened for correlation between environmental factors and
      lipid levels, utilizing four independent surveys with information on 188
      environmental factors from the Centers of Disease Control, National Health and
      Nutrition Examination Survey, collected between 1999 and 2006. METHODS: We used
      linear regression to correlate each environmental chemical factor to
      triglycerides, LDL-C and HDL-C adjusting for age, age(2), sex, ethnicity, socio
      economic status and body mass index. Final estimates were adjusted for waist
      circumference, diabetes status, blood pressure and survey. Multiple comparisons
      were controlled for by estimating the false discovery rate and significant
      findings were tentatively validated in an independent survey. RESULTS: We
      identified and validated 29, 9 and 17 environmental factors correlated with
      triglycerides, LDL-C and HDL-C levels, respectively. Findings include
      hydrocarbons and nicotine associated with lower HDL-C and vitamin E (gamma
      tocopherol) associated with unfavourable lipid levels. Higher triglycerides and
      lower HDL-C were correlated with higher levels of fat-soluble contaminants (e.g.
      polychlorinated biphenyls and dibenzofurans). Nutrients and vitamin markers (e.g.
      vitamins B, D and carotenes), were associated with favourable triglyceride and
      HDL-C levels. CONCLUSIONS: Our systematic association study has enabled us to
      postulate about broad environmental correlation to lipid levels. Although subject
      to confounding and reverse causality bias, these findings merit evaluation in
      additional cohorts.

PMID- 22421056
TI  - Stunting and obesity in childhood: a reassessment using longitudinal data from
      South Africa.
AB  - BACKGROUND: A series of cross-sectional studies have found a relationship between
      stunting and obesity in childhood. Because height appears in both the numerator
      of indices of stunting and the denominator of indices of obesity, random errors
      made by fieldworkers measuring heights can produce negative bias in estimates of
      this relationship. METHODS: With longitudinal data, height can be instrumented
      with its lagged value in a two-stage probit regression model, purging the
      estimated association between the probability of being obese or underweight and
      the height-for-age z-score of this errors-in-variables bias. Such a model is
      fitted to a cohort of 1110 primary-school-age children measured in 1993-2004 in a
      panel study in KwaZulu-Natal, South Africa. The study also collected detailed
      data on households' demographic and socio-economic characteristics. RESULTS: Risk
      factors for stunting, wasting and obesity differed in this population. Stunting
      was not associated with childhood obesity in either the cross-sectional or two
      stage models. In the cross-sectional analysis, however, random measurement errors
      masked a negative association between children's height-for-age and their
      probability of being underweight or wasted that emerged in the two-stage
      instrumental variable models. This association was further amplified, rather than
      attenuated, by controlling for children's household income, racial group,
      residence and mother's education. CONCLUSIONS: The validity of the findings of
      earlier cross-sectional studies of the association between stunting and obesity
      in childhood is dependent on the precision with which they measured height.
      Random measurement error can also mask an association between being stunted and
      underweight in cross-sectional studies.

PMID- 22421057
TI  - 8-alkylthio-6-thio-substituted theophylline analogues as selective noncompetitive
      progesterone receptor antagonists.
AB  - The progesterone receptor (PR) plays a key role in reproduction and is important
      in cancers of the reproductive tract. Current PR antagonists usually compete for
      progestin binding in the PR ligand-binding pocket and often exhibit cross-binding
      with other members of the steroid receptor family. Using stably transfected cells
      expressing reporter genes, a set of ~150 theophylline analogues were screened for
      their ability to inhibit progesterone, estrogen, glucocorticoid and androgen
      signaling. The structure-activity studies presented here identify branched 8
      alkylthio-6-thio-substitutions of theophylline as selective PR inhibitors. 6-Thio
      8-(2-ethylbutyl)thiotheophylline (51), the most extensively studied derivative,
      does not act by competing with progestins for binding in the ligand-binding
      pocket of PR. It demonstrated the ability to inhibit the mouse mammary tumor
      virus (MMTV)-luciferase reporter and endogenous PR-regulated alkaline phosphatase
      activity in T47D breast cancer cells. Compound 51 is the lead member of a novel
      class of PR inhibitors that act outside the PR ligand-binding pocket, thus
      serving as a novel probe to investigate PR action and a lead for further
      development.

PMID- 22421058
TI  - Delayed processing of bone marrow samples reveals a prognostic pattern of NME
      mRNA expression in cytogenetically normal acute myeloid leukemia.
AB  - Improvements in the therapy of cytogenetically normal acute myeloid leukemia (CN
      AML) will depend largely on the characterization of functional subtypes
      identified by prognostic markers. Exposing leukemic cells to stress ex vivo may
      reveal relevant phenotypic markers not apparent in freshly explanted cells. Here,
      we assess the prognostic relevance of expression of the nucleoside diphosphate
      kinase genes NME1 and NME2 in a cohort of 78 patients with CN-AML aged < 60 years
      using archived mononuclear cell samples originally prepared from bone marrow
      either directly (n = 25) or following 2-3 days of transport (n = 53). The stress
      conditions arising during transport resulted in the development of a prognostic
      pattern of NME mRNA with maintenance of high NME2 mRNA being a strong indicator
      of increased event-free survival independent of FLT3-internal tandem duplication.
      Prospective analysis of CN-AML bone marrow (n = 7) confirmed that NME1 mRNA is
      always decreased during storage, while NME2 mRNA is either decreased or
      maintained. We conclude that ex vivo stress can reveal novel prognostic markers.

PMID- 22421059
TI  - Symptoms, reasons for encounter and diagnoses. Family practice is an
      international discipline.

PMID- 22421060
TI  - Variability in the detection and monitoring of chronic patients in primary care
      according to what is registered in the electronic health record.
AB  - BACKGROUND: The electronic health record (EHR) allows a detailed study of the
      primary care consultations and assessment of variability among physicians
      regarding the implementation of practices for prevention, detection and
      monitoring of chronic diseases. OBJECTIVES: To describe the variability in the
      detection and surveillance of chronic conditions in primary care. METHODS: Review
      of the medical records maintained by 1685 primary care physicians in the Basque
      Health Service. Estimation of age and sex standardized rates of compliance with
      evidence-based recommendations and the systematic component of variation (SCV).
      RESULTS: Compliance with screening recommendations varied from 14.2% for chronic
      obstructive pulmonary disease (COPD) to 37.2% for hypercholesterolaemia of the at
      risk populations. Variability between Primary Care Units (PCUs) was low (SCV(5) (
      95) < 0.10) for high blood pressure, hypercholesterolaemia and diabetes and high
      (SCV(5) (-95) >= 0.20) for COPD. Based on the EHR registries, recommendations
      were followed to in at least 50% of relevant patients according to only 10 of the
      44 good care practice (GCP) criteria. For 16 of the GCP criteria, the EHR data
      indicated compliance to the recommendations in <25% of patients diagnosed.
      CONCLUSIONS: EHR data indicate that some of the preventative care practices
      recommended to detect chronic problems in primary care are unevenly implemented
      across PCUs. Notably, there is less variation in the case of conditions for which
      evidence-based clinical practice guidelines have been published. The level of
      monitoring is inadequate for all the conditions studied; particularly in those in
      which it is less evident that primary care is the right level of the health
      service to provide this care.

PMID- 22421061
TI  - Reappraisal of the electrographic manifestations of right ventricular apical
      pacing.

PMID- 22421063
TI  - Effect of Ag nanoparticle addition and ultrasonic treatment on a stable TiO2
      nanofluid.
AB  - Nanoparticles, when homogeneously dispersed in a base fluid, e.g. water, ethylene
      glycol etc. are commonly known as nanofluids. Nanofluids have gained attention in
      the scientific community for their enhanced thermal properties. One of the major
      problems in using nanofluids as a heat transfer medium for commercial
      applications is that, in most of the closed circuit industrial cooling processes,
      the cooling fluid has to be replaced after several cycles of cooling operation
      because of an increased presence of contaminants. If nanofluids were used as a
      coolant, it would be very hard to separate the nanoparticles from the waste
      fluid. The present work is aimed at the separation and recycling of nanoparticles
      from fluid waste by means of quick settling of titanium dioxide nanoparticles
      using silver nanoparticles along with ultrasonic treatment. It is observed that
      with increasing silver concentration and time of ultrasonication, the stability
      of the dispersion decreases. There is a value for both the silver concentration
      and ultrasonication time above which the settling time decreases drastically.

PMID- 22421062
TI  - Nucleosome positioning: bringing order to the eukaryotic genome.
AB  - Nucleosomes are an essential component of eukaryotic chromosomes. The impact of
      nucleosomes is seen not just on processes that directly access the genome, such
      as transcription, but also on an evolutionary timescale. Recent studies in
      various organisms have provided high-resolution maps of nucleosomes throughout
      the genome. Computational analysis, in conjunction with many other kinds of data,
      has shed light on several aspects of nucleosome biology. Nucleosomes are
      positioned by several means, including intrinsic sequence biases, by stacking
      against a fixed barrier, by DNA-binding proteins and by chromatin remodelers.
      These studies underscore the important organizational role of nucleosomes in all
      eukaryotic genomes. This paper reviews recent genomic studies that have shed
      light on the determinants of nucleosome positioning and their impact on the
      genome.

PMID- 22421064
TI  - A comparison between augmentation with olanzapine and increased risperidone dose
      in acute schizophrenia patients showing early non-response to risperidone.
AB  - We examined whether augmentation with olanzapine would be superior to increased
      risperidone dose among acute schizophrenia patients showing early non-response to
      risperidone. We performed a rater-blinded, randomized controlled trial at
      psychiatric emergency sites. Eligible patients were newly admitted patients with
      acute schizophrenia. Early response was defined as Clinical Global Impressions
      Improvement Scale score <=3 following 2 weeks of treatment. Early non-responders
      were allocated to receive either augmentation with olanzapine (RIS+OLZ group) or
      increased risperidone dose (RIS+RIS group). The 78 patients who completed 2 weeks
      of treatment were divided into 52 early responders to risperidone and 26 early
      non-responders to risperidone (RIS+OLZ group, n=13; RIS+RIS group, n=13). No
      difference in the achievement of >=50% improvement in Positive and Negative
      Syndrome Scale total score was observed between RIS+OLZ and RIS+RIS groups.
      Although time to treatment discontinuation for any cause was significantly
      shorter in the RIS+RIS group (6.8 weeks [95% confidence interval, 5.2-8.4]) than
      in early responders to risperidone (8.6 weeks [7.9-9.3]; P=0.018), there was no
      significant difference between the RIS+OLZ group (7.9 weeks [6.3-9.5]) and early
      responders to risperidone. Secondary outcomes justify the inclusion of
      augmentation arms in additional, larger studies comparing strategies for early
      non-responders.

PMID- 22421065
TI  - One-year functional outcomes of naturalistically treated patients with
      schizophrenia.
AB  - Against the background of the growing evidence that the patient's functioning
      significantly influences the course and outcome of schizophrenia, the aims of
      this analysis were to examine what proportion of patients achieve functional
      outcome criteria after 1 year, and to identify clinical and sociodemographic
      predictive factors for functional remission. Patients with the diagnosis of
      schizophrenia who were treated as inpatients at the beginning of the study were
      examined within a naturalistic follow-up trial. The present study reports on the
      time frame from admission to discharge of an inpatient treatment period and the 1
      year follow-up assessment. The Global Assessment of Functioning (GAF) Scale and
      Social and Occupational Functioning Assessment Scale (SOFAS) were evaluated with
      respect to functional outcome, whereas Positive and Negative Syndrome Scale
      (PANSS) scores were rated as psychopathological outcome measures. Functional
      remission thresholds were defined according to a GAF score of >=61 points and a
      SOFAS score >=61 points. Symptomatic remission criteria were applied according to
      the remission criteria of the Schizophrenia Working Group. The Strauss-Carpenter
      Prognostic Scale (SCPS), the Phillips Premorbid Adjustment Scale, medical
      history, sociodemographic and psychopathologic parameters were evaluated in order
      to find valuable predictors for functional remission. One year after discharge
      from inpatient treatment, 211 out of 474 patients were available for analysis
      according to both rating scales used to assess functional remission (GAF and
      SOFAS). Forty-seven percent of patients fulfilled criteria for functional
      remission (GAF and SOFAS) at discharge and 51% of patients at the 1-year follow
      up visit. With regard to symptomatic remission criteria, the corresponding
      remitter rates were 61% of patients at discharge and 54% at the 1-year follow-up
      visit. Forty-two percent of patients fulfilled both remission criteria at
      discharge and 37% at the 1-year follow-up visit. A significant association was
      found between functional and symptomatic remission at discharge and at the 1-year
      follow-up visit. The strongest predictors for functional remission at the 1-year
      follow-up visit were: a higher SCPS total score at admission, a lower number of
      previous hospitalizations, a status of employment, lower scores in all PANSS
      subscales at discharge, a better premorbid social adjustment, the occurrence of a
      first psychotic episode, a younger age, a lower PANSS negative subscore at
      admission, a status of being an early responder, a shorter duration of inpatient
      treatment, a later age of onset, and female gender.

PMID- 22421066
TI  - Risky decision-making in borderline personality disorder.
AB  - Impulsivity is a core feature of borderline personality disorder (BPD). Thereby,
      individuals with BPD are most often explicitly aware of the deleterious long-term
      consequences of their impulsive behaviors, but still engage in them. Therefore,
      the aim of the present study was to test decision-making in BPD. Female
      individuals with BPD (n=21) and female controls without BPD (CG; n=29) were
      compared on the Game of Dice Task (GDT) with regard to disadvantageous decision
      making and feedback processing. In the GDT rules for reinforcement and punishment
      are explicitly clear and the outcome is defined by probabilities. By providing
      feedback about the outcome of previous decisions, the GDT is a valid measure to
      simulate decision-making in real life situations. Main results revealed that
      women with BPD make risky decisions significantly more often than the CG.
      Moreover, they show reduced capacities to advantageously utilize feedback. As
      deficits in decision-making were correlated with BPD symptom severity and
      impulsivity, risky decision-making may be a relevant maintenance factor for the
      disorder.

PMID- 22421067
TI  - Facets of psychopathy among mentally disordered offenders: clinical comorbidity
      patterns and prediction of violent and criminal behavior.
AB  - The complexity and consequences of psychopathy are still debated, and its
      relation to other mental disorders, pathological personality traits, and
      criminality needs to be further investigated by clinical, longitudinal studies
      using structured diagnostic instruments. The present study used two groups of
      mentally disordered offenders (N=153) investigated with in-depth clinical
      assessments and prospective long-term follow-up to identify the convergence
      between 1) the four facets of psychopathy defined by the Psychopathy Checklist
      Revised (PCL-R; Interpersonal, Affective, Lifestyle, and Antisocial), 2) mental
      disorders according to SCID I and II interviews, 3) personality traits as
      measured by the Karolinska Scales of Personality, and 4) criminal recidivism. The
      Interpersonal facet differed substantially from the other three facets by not
      being significantly associated with substance use disorders, antisocial
      personality disorder (the other facets at P<=0.001 level), or personality traits
      involving impulsive and aggressive antisocial behaviors (the other facets at
      P<0.01 level). Furthermore, the interpersonal facet could not predict violent
      recidivism better than random. The Antisocial facet outperformed not only the
      other facets but also the total PCL-R score in the prediction of violent
      recidivism, P<0.001.The findings confirm psychopathy as a heterogeneous
      phenomenon and have clinical implications for assessments of psychopathy and
      violence risk assessments in clinical and forensic contexts.

PMID- 22421068
TI  - Medically treated anorexia nervosa is associated with normal P wave parameters.
AB  - Anorexia nervosa (AN) is an increasingly common medical condition. Some studies
      have demonstrated an increased prevalence of atrial premature contractions and
      anatomical changes in AN patients. Our aim was to investigate P wave parameters
      and P wave dispersion, an electrocardiographic marker for supraventricular
      arrhythmias, and its effect on AN. The study group included 48 patients with AN,
      most hospitalized for a few weeks, and a matched control group. All participants
      underwent 12-lead electrocardiography (ECG) under strict standards. P wave length
      and P wave dispersion in each patient were computed from a randomly selected beat
      and an averaged beat, constructed from 7 to 12 beats, included in a 10-s ECG.
      There were no statistically significant differences found between the groups for
      minimal, maximal, average P wave duration and P wave dispersion, calculated
      either from a random beat or averaged beats. In conclusion, medically treated AN
      patients who have gained weight have normal P wave parameters, and therefore do
      not appear to have an increased electrocardiographic risk for atrial fibrillation
      compared with healthy controls. Further studies are required to evaluate the
      influence of different disease stages, electrolyte imbalance and other medical
      complications on P wave parameters and risk for supraventricular arrhythmias in
      AN patients.

PMID- 22421069
TI  - Potential role of cortical 5-HT(2A) receptors in the anxiolytic action of
      cyamemazine in benzodiazepine withdrawal.
AB  - The antipsychotic cyamemazine is a potent serotonin 5-HT(2A) receptor (5-HT(2AR))
      antagonist. A positron emission tomography (PET) study in human patients showed
      that therapeutic doses of cyamemazine produced near saturation of 5-HT(2AR)
      occupancy in the frontal cortex, whereas dopamine D(2) occupancy remained below
      the level for motor side effects observed with typical antipsychotics. Recently,
      numerous studies have revealed the involvement of 5-HT(2AR) in the
      pathophysiology of anxiety and a double-blind, randomized clinical trial showed
      similar efficacy of cyamemazine and bromazepam in reducing the anxiety associated
      with benzodiazepine withdrawal. Therefore, we reviewed the above articles about 5
      HT(2AR) and anxiety in order to understand better the anxiolytic mechanisms of
      cyamemazine in benzodiazepine withdrawal. The 5-HT(2AR) is the most abundant
      serotonin receptor subtype in the cortex. Non-pharmacological studies with
      antisense oligodeoxynucleotides and genetically modified mice clearly showed that
      cortical 5-HT(2AR) signaling positively modulates anxiety-like behavior. With a
      few exceptions, most other studies reviewed here further support this view.
      Therefore, the anxiolytic efficacy of cyamemazine in benzodiazepine withdrawal
      can be due to a 5-HT(2AR) antagonistic activity at the cortical level.

PMID- 22421071
TI  - Is autism spectrum disorder common in schizophrenia?
AB  - A century ago, Kraepelin and Bleuler observed that schizophrenia is often
      antedated by "premorbid" abnormalities. In this study we explore how the
      childhood neurodevelopmental problems found in patients with schizophrenia relate
      to the current concept of autism spectrum disorder (ASD). Forty-six young adult
      individuals with clinical diagnoses of schizophrenic psychotic disorders were
      assessed. The Structured Clinical Interview for DSM Disorders (SCID-I) was used
      in face-to-face psychiatric examination of each individual. In 32 of the 46 cases
      (70%), collateral information was provided by one or both parents. The Diagnostic
      Interview for Social and Communication Disorders - eleventh version (DISCO-11)
      was used when interviewing these relatives. This instrument covers, in
      considerable depth, childhood development, adaptive functioning, and symptoms of
      ASD - current and lifetime. There is a strict algorithm for ASD diagnosis. About
      half of the cases with schizophrenic psychosis had ASD according to the results
      of the parental interview. The rate of ASD was strikingly high (60%) in the group
      with a SCID-I diagnosis of schizophrenia paranoid type. The findings underscore
      the need to revisit the DSM's "either or" stance between ASD and schizophrenia.

PMID- 22421070
TI  - The developmental origins of externalizing behavioral problems: parental
      disengagement and the role of gene-environment interplay.
AB  - A line of research has revealed that the influence of genes on behavioral
      development is closely tied to environmental experiences. Known as gene
      environment interaction, research in this area is beginning to reveal that
      variation in parenting behaviors may moderate genetic influences on antisocial
      behaviors in children. Despite growing interest in gene-environment interaction
      research, little evidence exists concerning the role of maternal disengagement in
      the conditioning of genetic influences on childhood behavioral problems. The
      current study is intended to address this gap in the literature by analyzing a
      sample of twin pairs drawn from the Early Childhood Longitudinal Study, Birth
      Cohort (ECLS-B). Analysis of the ECLS-B provided evidence that maternal
      disengagement moderates genetic influences on the development of externalizing
      problems.

PMID- 22421072
TI  - Cognitive factors associated with subclinical delusional ideation in the general
      population.
AB  - Cognitive biases have been found to be associated with delusions in schizophrenia
      and schizotypy. In the current study, we examined the relationship between
      subclinical delusional ideation, measured using the Peters Delusions Inventory,
      and cognitive biases including the bias against disconfirmatory evidence (BADE),
      'jumping to conclusions', and need for closure, evaluated using the computerized
      BADE program, in a sample of 117 healthy, non-psychiatric controls. Our results
      suggest that subclinical delusional ideation is associated with BADE, greater
      need for closure, a 'jumping to conclusions' response style, and a tendency to
      rate absurd and unlikely interpretations of an event as more plausible, which
      might be indicative of insufficient evidence integration or 'liberal acceptance'.
      These cognitive biases, which occur in a much milder fashion than seen in typical
      deluded patient samples, may nonetheless additively play a role in the
      development of delusional ideation, and suggest common pathways seen in healthy
      and psychiatric samples.

PMID- 22421073
TI  - Investigation of impulsivity in a sample of treatment-seeking pathological
      gamblers: a multidimensional perspective.
AB  - Numerous studies have shown that problem gambling is characterised by lack of
      impulse control. However, they have often been conducted without considering the
      multifaceted nature of impulsivity and related psychological mechanisms. The
      current study aims to disentangle which impulsivity facets are altered in
      pathological gambling. Twenty treatment-seeking pathological gamblers (PGs) and
      20 matched control participants completed a self-reported questionnaire measuring
      the various facets of impulsive behaviours (UPPS Impulsive Behaviour Scale), as
      well as two laboratory tasks assessing inhibitory control (the go-stop task) and
      tolerance for delayed rewards (single key impulsivity paradigm). Compared with
      matched controls, PGs exhibited higher urgency, lower premeditation, impairment
      in prepotent inhibition, and lower tolerance towards delayed rewards.
      Nevertheless, complementary profile analyses showed that impulsivity-related
      deficits found in PGs are highly heterogeneous, and that some PGs are neither
      impulsive in the impulsivity facets assessed nor impaired in the cognitive
      mechanisms measured. These findings underscore (1) the necessity to disentangle
      the construct of impulsivity into lower-order components and (2) that further
      studies should take into account, in addition to impulsivity-related mechanisms,
      other psychological factors potentially involved in pathological gambling.

PMID- 22421074
TI  - Descriptive and numeric estimation of risk for psychotic disorders among affected
      individuals and relatives: implications for clinical practice.
AB  - Studies show that individuals with psychotic illnesses and their families want
      information about psychosis risks for other relatives. However, deriving accurate
      numeric probabilities for psychosis risk is challenging, and people have
      difficulty interpreting probabilistic information; thus, some have suggested that
      clinicians should use risk descriptors, such as "moderate" or "quite high",
      rather than numbers. Little is known about how individuals with psychosis and
      their family members use quantitative and qualitative descriptors of risk in the
      specific context of chance for an individual to develop psychosis. We explored
      numeric and descriptive estimations of psychosis risk among individuals with
      psychotic disorders and unaffected first-degree relatives. In an online survey,
      respondents numerically and descriptively estimated risk for an individual to
      develop psychosis in scenarios where they had: A) no affected family members; and
      B) an affected sibling. Participants comprised 219 affected individuals and 211
      first-degree relatives participated. Affected individuals estimated significantly
      higher risks than relatives. Participants attributed all descriptors between
      "very low" and "very high" to probabilities of 1%, 10%, 25% and 50%+. For a given
      numeric probability, different risk descriptors were attributed in different
      scenarios. Clinically, brief interventions around risk (using either
      probabilities or descriptors alone) are vulnerable to miscommunication and
      potentially negative consequences-interventions around risk are best suited to in
      depth discussion.

PMID- 22421075
TI  - Utility of a focused vancomycin-resistant enterococci screening protocol to
      identify colonization in hospitalized children.
AB  - Screening for vancomycin-resistant enterococci (VRE) is controversial, and
      disagreement exists on policy implementation. This study investigated the
      likelihood of a positive test using 1, 2, or 3 rectal screenings for VRE
      colonization. In this descriptive study of positive VRE screening cultures, a
      total of 1211 VRE screens identified 41 positive results. The mean age of these
      positive patients was 5.7 years. Thirty-nine of the 41 had a chronic illness, and
      only 2 were healthy. Diagnoses included pulmonary disease in 11 patients and
      chronic gastrointestinal abnormality in 7. Six patients had been born preterm,
      and 12 had been treated in a neonatal intensive care unit within the previous 6
      months. Thirty-six of the 41 positive results were identified on the first
      screen. The likelihood of subsequently having a positive screen after a negative
      screen was 0.43% (95% confidence interval, 0.15%-1.02%). The cost of cultures
      plus isolation was $50,000 for the study period. Our data show that the
      likelihood of detecting a positive VRE culture after an initial negative was low,
      particularly in otherwise healthy children.

PMID- 22421076
TI  - High fecal hand contamination among wilderness hikers.
AB  - Information about hand hygiene and fecal hand contamination among the general
      public is limited. Hands are an important vector in transmission of various
      pathogenic bacteria. We found high (31%) prevalence of fecal hand contamination
      among healthy adults engaged in hiking.

PMID- 22421077
TI  - Interpretation of positive predictive values of claims-based algorithms.

PMID- 22421078
TI  - Fabrication and characterization of a solid-state nanopore with self-aligned
      carbon nanoelectrodes for molecular detection.
AB  - Stochastic  molecular  sensors based on resistive pulse nanopore modalities are
      envisioned as facile DNA sequencers. However, recent advances in nanotechnology
      fabrication have highlighted promising alternative detection mechanisms with
      higher sensitivity and potential single-base resolution. In this paper we present
      the novel self-aligned fabrication of a solid-state nanopore device with
      integrated transverse graphene-like carbon nanoelectrodes for polyelectrolyte
      molecular detection. The electrochemical transduction mechanism is characterized
      and found to result primarily from thermionic emission between the two transverse
      electrodes. Response of the nanopore to Lambda dsDNA and short (16-mer) ssDNA is
      demonstrated and distinguished.

PMID- 22421079
TI  - Is there currently enough evidence to assess whether laparoscopic
      nephroureterectomy is safe to treat urothelial carcinoma of the upper urinary
      tract?

PMID- 22421080
TI  - Prediction of functional outcomes after nerve-sparing radical prostatectomy:
      results of conditional survival analyses.
AB  - BACKGROUND: In prostate cancer (PCa) patients treated with radical prostatectomy
      (RP), the rate of urinary continence (UC) and erectile function (EF) recovery may
      change significantly depending on the time interval between surgery and patient
      assessment. This effect, known as conditional survival, has not yet been
      assessed. OBJECTIVE: Evaluate the conditional rates of UC and EF recovery after
      nerve-sparing RP (NSRP). DESIGN, SETTING, AND PARTICIPANTS: We included 1135 PCa
      patients treated between January 2000 and June 2011 at a single referral center.
      INTERVENTION: All patients underwent NSRP. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: The Kaplan-Meier method assessed the time to recovery of UC (defined as
      an International Consultation on Incontinence Questionnaire score<6) and of EF
      (defined as an International Index of Erectile Function-Erectile Function
      score>=22). Cumulative survival estimates were used to generate conditional
      recovery rates assessed at a 6-mo interval. Multivariable Cox regression analyses
      were performed to predict functional outcomes recovery after accounting for
      confounders. RESULTS AND LIMITATIONS: UC recovery rates were 89.5%, 94.7%, and
      97.0% at 6-, 24-, and 36-mo follow-up, respectively. Corresponding EF recovery
      rates were 53.6%, 65.0%, and 67.5%, respectively. In patients who were still
      incontinent at 1, 6, 12, 18, 24, 30, and 36 mo after surgery, UC recovery rates
      in the following 6-mo period significantly decreased as the time from surgery
      increased: 74.9%, 58.2%, 41.4%, 14.9%, 24.8%, 24.6%, and 13.3%, respectively.
      Similarly, in patients still impotent at the same time points, the 6-mo rate of
      sexual potency recovery was 36.9%, 26.8%, 17.8%, 8.2%, 3.1%, 4.0%, and 0%,
      respectively. Multivariable analyses confirmed these results. The study is
      limited by its retrospective design. CONCLUSIONS: In incontinent and/or impotent
      patients, the period elapsed from surgery represents an important predictor of
      the recovery of subsequent functional outcomes. The highest increments in UC and
      EF recovery were observed during the first year after surgery; they were
      virtually null after 36 mo.

PMID- 22421081
TI  - Salvage cryoablation for locally recurrent prostate cancer following primary
      radiotherapy.
AB  - CONTEXT: The purpose of this paper is to review current salvage cryoablation
      (SCA) outcomes in patients with locally recurrent prostate cancer (PCa) following
      primary radiation therapy. OBJECTIVE: The objectives of this review are (1) to
      analyze the eligibility criteria for careful patient selection for these salvage
      modalities and (2) to evaluate the oncologic results and reported complication
      rates for these respective modalities. EVIDENCE ACQUISITION: A Medline/PubMed
      literature search was performed of peer-reviewed scientific articles published
      from 1991 to 2012 regarding salvage therapy for radiorecurrent PCa. The following
      search terms and various permutations were used: radiorecurrent prostate cancer,
      local salvage treatment, salvage radical prostatectomy, salvage cryoablation,
      salvage brachytherapy, and salvage high-intensity focused ultrasound. Only
      articles written in English were included. EVIDENCE SYNTHESIS: SCA is a feasible
      and efficacious treatment modality, especially using third-generation technology,
      whereby the biochemical disease-free survival is estimated to be between 50% and
      70% at 5-yr follow-up in properly selected patients. Severe complications such as
      rectourethral fistulas are significantly less common over the last decade than
      was reported in the past. Because there are no prospective, randomized studies
      and the definitions of PSA failure vary among many studies, comparisons between
      these different salvage modalities are limited in terms of cancer-specific
      outcomes. Nevertheless, in recent years, tertiary care referral centers for
      prostate cryotherapy have reported their treatment outcomes using rigorous
      treatment end points and morbidity grading systems, dramatically improving the
      quality of reported clinical data. Consequently, favorable predictors of
      treatment outcomes have been identified. CONCLUSIONS: The inability to
      effectively salvage patients with locally recurrent PCa following radiation
      therapy has in large part resulted from the lack of sufficiently sensitive and
      specific diagnostic tools to detect local recurrences at an early, potentially
      curable stage. Consequently, a more stringent definition of biochemical failure,
      improved imaging techniques, and accurate PCa mapping imaging technology is
      greatly needed within our diagnostic armamentarium. Additional research and
      randomized clinical trials are required to determine which salvage modality is
      superior in terms of oncologic efficacy and reduced morbidity.

PMID- 22421082
TI  - Treatment of carcinoma in situ of the glans penis with topical chemotherapy
      agents.
AB  - BACKGROUND: The use of topical agents in the treatment of carcinoma in situ (CIS)
      of the penis has been well described in the literature. Previous studies have
      been limited by small sample size and imprecise end points. OBJECTIVE: Establish
      the response rate of 5-fluorouracil (5-FU) and imiquimod (IQ) in the treatment of
      penile CIS in a large contemporary series in a supranetwork centre. DESIGN,
      SETTING, AND PARTICIPANTS: Retrospective review of all primary and recurrent
      cases of penile CIS treated with 5-FU and IQ identified from a prospective
      database over a 10-yr period. Therapy was standardised in all cases with
      application to the lesion for 12h every 48 h for 28 d. INTERVENTION: 5-FU was the
      first-line therapy, and IQ was the second-line topical agent. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was defined as
      complete response (CR; i.e., resolution of lesion), partial response (PR; i.e.,
      lesion reduced in size and or visibility), or no response (NR; ie, no improvement
      in lesion size and or visibility). The secondary end points included local
      toxicity and adverse events. No statistical analysis or software was used.
      RESULTS AND LIMITATIONS: A total of 86 patients were diagnosed with CIS of the
      penis over the 10-yr period. Forty-four (51%) received topical chemotherapy. The
      mean follow-up was 34 mo. CR to topical chemotherapy was seen in 25 (57%), PR was
      seen in 6 (13.6%), and NR was seen in the remaining 13 (29.5%) patients. Local
      toxicity was experienced by 10% of patients, and 12% had an adverse event
      following application of 5-FU. The retrospective design and short follow-up were
      the major limitations of this study. CONCLUSIONS: Topical chemotherapy agents are
      moderately effective first-line therapy in the treatment of penile CIS. Toxicity
      and adverse events were few with our treatment protocol. The issues of long-term
      surveillance and assessment of partial responders remain a challenge. Topical
      chemotherapy should remain a first-line treatment option for penile CIS.

PMID- 22421083
TI  - A contemporary update on pathology reporting for prostate cancer: biopsy and
      radical prostatectomy specimens.
AB  - CONTEXT: The diagnosis of and reporting parameters for prostate cancer (PCa) have
      evolved over time, yet they remain key components in predicting clinical
      outcomes. OBJECTIVE: Update pathology reporting standards for PCa. EVIDENCE
      ACQUISITION: A thorough literature review was performed for articles discussing
      PCa handling, grading, staging, and reporting published as of September 15, 2011.
      Electronic articles published ahead of print were also considered. Proceedings of
      recent international conferences addressing these areas were extensively
      reviewed. EVIDENCE SYNTHESIS: Two main areas of reporting were examined: (1)
      prostatic needle biopsy, including handling, contemporary Gleason grading, extent
      of involvement, and high-risk lesions/precursors and (2) radical prostatectomy
      (RP), including sectioning, multifocality, Gleason grading, staging of organ
      confined and extraprostatic disease, lymph node involvement, tumor volume, and
      lymphovascular invasion. For each category, consensus views, controversial areas,
      and clinical import were reviewed. CONCLUSIONS: Modern prostate needle biopsy and
      RP reports are extremely detailed so as to maximize clinical utility. Accurate
      diagnosis of cancer-specific features requires up-to-date knowledge of grading,
      quantitation, and staging criteria. While some areas remain controversial,
      efforts to codify existing knowledge have had a significant impact on pathology
      practice.

PMID- 22421084
TI  - Editorial for effect of dornase alfa on inflammation and lung function: potential
      role in the early treatment of cystic fibrosis.

PMID- 22421085
TI  - Phylogeny and diversification of Valerianaceae (Dipsacales) in the southern
      Andes.
AB  - The southern Andean clade of Valeriana provides an excellent model for the study
      of biogeography. Here we provide new data to help clarify phylogenetic
      relationships among the South American valerians, with special focus on taxa
      found in the southern Andes. We found that the southern Andean taxa formed a
      clade in maximum likelihood and maximum parsimony analyses, and used a Bayesian
      relaxed clock method to estimate divergence times within Valerianaceae. Our
      temporal results were similar to other studies, but we found greater variance in
      our estimates, suggesting that the species of Valeriana have been on the South
      American continent for some time, and have been successful at exploiting new
      niche opportunities that reflects the contemporary radiation. Regardless of the
      time frame for the radiation of the clade, the uptick in the rate of
      diversification in Valerianaceae appears correlated with a dispersal event from
      Central to South America. The appearance of Valeriana in the southern Andes (13.7
      Ma) corresponds with the transition from closed forest on the western side of the
      Andes in central Chile to a more open Mediterranean woodland environment. This
      would suggest that the high species richness of Valerianaceae in South America is
      the result of multiple, smaller radiations such as the one in the southern Andes,
      that may or may not be geographically isolated. These smaller radiations may also
      be driven by species moving into new biomes (migration from a temperate to a more
      Mediterranean-type climate and into alpine). The degree to which different
      ecological and geological factors interact to drive diversification is difficult
      to ascertain. Likewise, without a better-resolved phylogeny it is impossible to
      determine the directionality of dispersal in this group; did they colonize the
      southern Andes first, then move northward as the central Andean alpine habitat
      became more widely available or vice versa?

PMID- 22421086
TI  - Tuberculosis: burning issues: multidrug resistance and HIV-coinfection.
AB  - Tuberculosis is an infection of respiratory tract and Mycobacterium tuberculosis
      is the causative agent. Multidrug resistance and HIV-coinfection are the burning
      issues for tuberculosis. The management of drug resistance to tuberculosis is the
      necessity of the day so by taking effective and controlled measures and giving
      high doses of 2nd line drugs, we can minimize the death rate in TB. For the HIV
      related TB infection, it is necessary to treat TB infection first so that
      effectiveness of antiretroviral therapy may not be altered and the transmission
      of M. tuberculosis to other healthy individuals of community could be prevented.
      All HIV positive individuals who are at a greater risk of acquiring TB infection,
      either due to suppressed immune system or unhealthy circumstances, must be
      investigated and if indicated must be treated effectively at immediate basis so
      that latent TB infection may not progress to active TB.

PMID- 22421087
TI  - Insight on trace element detoxification in the Black-tailed Godwit (Limosa
      limosa) through genetic, enzymatic and metallothionein analyses.
AB  - Trace element concentrations (Ag, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, Zn)
      were investigated in the liver, kidneys, muscle and feathers of 31 black-tailed
      godwits (Limosa limosa) accidentally killed during catches by mist net in the
      Pertuis Charentais, Atlantic coast of France. Analyses of carbon and nitrogen
      stable isotope ratios were carried out in liver, muscle and feathers in order to
      elucidate dietary patterns and to determine whether differences in diet explained
      the variation in elemental uptake. This study also aimed to have a preliminary
      assessment of sub-lethal effects triggered by trace elements through the
      investigation of gene expressions by quantitative real-time PCR, antioxidant
      enzyme activities (catalase, superoxide dismutase, glutathione peroxidase), and
      metallothionein (MT) levels. The results showed that Cr and Ni concentrations in
      tissues of adults were lower than in juveniles in part because adults may have
      eliminated these trace elements through moulting. Except for Cd and Ni, trace
      element concentrations were negatively correlated to the body mass of godwits.
      Ag, As, Hg and Se concentrations were positively linked with the trophic position
      of birds. The diet could be considered as a fundamental route of exposure for
      these elements demonstrating therefore the qualitative linkage between dietary
      habits of godwits and their contaminant concentrations. Our results strongly
      suggest that even though trace element concentrations were mostly below toxicity
      threshold level, the elevated concentrations of As, Ag, Cd, Cu, Fe and Se may
      however trigger sub-lethal effects. Trace elements appear to enhance expression
      of genes involved in oxidative stress defence, which indicates the production of
      reactive oxygen species. Moreover, birds with the highest concentrations appeared
      to have an increased mitochondrial metabolism suggesting that the fight against
      trace element toxicity requires additional energetic needs notably to produce
      detoxification mechanisms such as metallothioneins.

PMID- 22421088
TI  - Acute effects of electromagnetic fields emitted by GSM mobile phones on
      subjective well-being and physiological reactions: a meta-analysis.
AB  - The potential effects of radiofrequency electromagnetic fields (RF-EMF) emitted
      by GSM mobile phones on subjective symptoms, well-being and physiological
      parameters have been investigated in many studies. However, the results have been
      ambiguous. The current meta-analysis aims to clarify whether RF-EMF have an
      influence on well-being in self-reported sensitive persons, as well as in non
      sensitive people. A literature search revealed 17 studies including 1174
      participants. The single effects for various subjective and objective outcomes
      were meta-analytically combined to yield a single population parameter. Dependant
      variables were subjective (e.g. headaches) and objective parameters (e.g. heart
      rate variability) of well-being. The results show no significant impact of short
      term RF-EMF exposure on any parameter. Future research should focus on the
      possible effects of long-term exposure.

PMID- 22421089
TI  - Levels of persistent organic pollutants in larvae of the damselfly Ischnura
      elegans (Odonata, Coenagrionidae) from different ponds in Flanders, Belgium.
AB  - We investigated the accumulation of persistent organic pollutants in damselfly
      larvae (Ischnura elegans) in sixteen ponds in Flanders (Belgium), widely
      differing in the surrounding land use. Concentrations of polychlorinated
      biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), p,p'
      dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB) were
      measured. From all targeted PBDE-congeners, only three congeners (IUPAC nos. 47,
      99, 100) were above the limit of quantification (LOQ). The ?PBDE concentrations
      ranged from <LOQ up to 0.51 ngg(-1) ww. From the targeted PCB-congeners, thirteen
      were detectable (IUPAC nos. 95, 99, 101, 105, 118, 138, 149, 153, 156, 170, 180,
      183, and 187). A high variation in ?PCB concentrations was observed between the
      ponds, ranging from <LOQ (0.67 ngg(-1) ww) up to 9.91 ngg(-1) ww in the
      damselflies from the pond at Sijsele. In all investigated Flemish ponds, p,p'-DDE
      concentrations were >LOQ (0.20 ngg(-1) ww) with values up to 3.30 ngg(-1) ww in
      the pond at Hamme. In fifteen ponds, the HCB concentrations were >LOQ (0.05 ngg(
      1) ww) with values up to 0.24 ngg(-1) ww. For the available data in the
      literature a comparison with different species was done for some of the sampled
      ponds. The monitored ponds can be separated in three groups based on their
      contamination. The first group is characterised by a relative low POP content
      (?PBDEs, ?PCBs, HCB). Group 2 contained more HCB and p,p'-DDE than the overall
      mean while this was the case for PBDEs and PCBs in group 3. The vectors of both
      contaminated groups are situated nearly perpendicular which is suggesting a
      different pollution sources.

PMID- 22421090
TI  - Measuring nonpolar organic contaminant partitioning in three Norwegian sediments
      using polyethylene passive samplers.
AB  - Freely dissolved pore water concentrations of polycyclic aromatic hydrocarbons
      (PAHs), polychlorinated biphenyls (PCBs), penta- and hexachlorobenzene (PeCB and
      HCB), octachlorostyrene (OCS), p,p'-DDE and p,p'-DDD were measured in bottom
      sediments from three sites in Norway. Sediments were from Aker Brygge, site of a
      former shipyard in the inner part of Oslofjord, Frierfjord in the Grenlandsfjord
      area, impacted during the 50 year-long activity of a magnesium smelter plant, and
      from Kristiansand harbour, site with high industrial activity. Low density
      polyethylene (LDPE) membrane samplers were exposed to these sediments in
      laboratory incubation under constant and low-level agitation for periods of 1, 2,
      6, 13, 23 and 50 days. Freely dissolved pore water concentrations were estimated
      from contaminant masses accumulated and sampling rates obtained from the
      measurement of kinetics of dissipation of performance reference compounds (PRCs).
      Marked differences in freely dissolved PAH concentrations and resulting organic
      carbon-normalised sediment-pore water partition coefficients, logK(TOC), between
      these three sediments could be observed despite the generally similar total
      sediment concentrations. In contrast with the PAH data, partitioning of PCBs and
      other organochlorine compounds (OCs) was relatively similar in all three
      sediments. For sediments from Frierfjord and Kristiansand, logK(TOC) values were
      lower for PCBs/OCs than for PAHs, indicating higher availability. Similar
      partitioning of PAHs and PCBs/OCs was found for sediments from Aker Brygge. No
      simple logK(oc)-logK(ow) relationships could model these data successfully. These
      results support the notion that the assessment of the risk posed by these
      compounds present in sediments in most cases requires actual measurement of
      contaminant availability.

PMID- 22421091
TI  - Epigallocatechin-3-gallate (EGCG) enhances the therapeutic activity of a dental
      adhesive.
AB  - OBJECTIVES: The purpose of this study was to evaluate the antibacterial potential
      and physicochemical properties of a dental adhesive incorporated with
      epigallocatechin-3-gallate (EGCG) in different concentration over time. METHODS:
      EGCG was incorporated at a ratio of 100, 200, and 300 MUg/ml into a dental
      adhesive. The effects of the cured adhesives on the growth of Streptococcus
      mutans were determined by direct contact test immediately or one month later and
      by scanning electron microscopy (SEM), respectively. Microtensile bond strength
      (MUTBS) test was used to test the mechanical property of the adhesives
      immediately or six months later. The degree of conversion (DC) of the adhesives
      was evaluated by Fourier transform infrared spectroscopy (FTIR). RESULTS:
      Compared with negative control, the 200 MUg/ml and 300 MUg/ml EGCG-incorporated
      dental adhesive were found to exhibit inhibitory effect on the growth of S.
      mutans. The MUTBS of the EGCG-incorporated dental adhesive was higher than the
      control. The DC of the adhesive system was not affected by the addition of EGCG.
      CONCLUSIONS: 200 MUg/ml EGCG incorporated dental adhesives could accomplish
      therapeutic goals that play in antimicrobial function whilst keeping the
      durability of resin-dentine bond.

PMID- 22421092
TI  - Effect of low pH on surface rehardening efficacy of high concentration fluoride
      treatments on non-cavitated lesions.
AB  - OBJECTIVE: Professionally applied acidulated phosphate fluoride has been shown to
      reduce caries incidence. However, it has been suggested that its efficacy might
      be reduced in advanced non-cavitated lesions. This study aimed to compare the
      surface rehardening and fluoride uptake effect of 2%-NaF solutions at different
      pH on non-cavitated caries-like lesions with two different levels of
      demineralization. METHODS: Human enamel specimens were demineralized to create
      early and advanced non-cavitated lesions. Specimens for each type of lesion were
      divided into 3 groups, treated for four minutes with either 2%-NaF pH 3.5, 2%-NaF
      at pH 7.0, or neutral deionized water, and exposed to a pH cycling
      remineralization/demineralization model for five days. An additional treatment
      was then done as described above followed by five more days of cycling (total of
      2 treatments, ten-day pH cycling). Specimens were analyzed for surface
      microhardness change and fluoride uptake. RESULTS: It was found that for both
      types of lesions, acidic pH fluoride treatment was significantly (p<0.05) more
      effective than neutral pH treatment in rehardening the lesion surface and
      promoting fluoride uptake. Furthermore, the low pH vs neutral pH difference in
      rehardening was significantly larger in the less demineralized lesions
      (p=0.0001). Water treatment resulted in no rehardening or fluoride uptake.
      CONCLUSIONS: Results from this study suggest that high concentration fluoride
      treatments at acidic pH are more effective in rehardening the surface of non
      cavitated caries lesions and promoting fluoride uptake than those at neutral pH.
      This effect appears to be greater in less demineralized lesions when compared to
      more advanced ones. CLINICAL SIGNIFICANCE: The results of this investigation
      suggest that when no other attenuating circumstances are present (e.g., the
      possibility of damaging tooth-coloured restorations), high concentration fluoride
      treatments for high risk individuals might be more efficacious using products at
      low pH.

PMID- 22421093
TI  - Effect of limbal marking prior to laser ablation on the magnitude of
      cyclotorsional error.
AB  - PURPOSE: To evaluate the residual registration error after limbal-marking-based
      manual adjustment in cyclotorsional tracker-controlled laser refractive surgery.
      METHODS: Two hundred eyes undergoing custom surface ablation with the iVIS Suite
      (iVIS Technologies) were divided into limbal marked (marked) and non-limbal
      marked (unmarked) groups. Iris registration information was acquired
      preoperatively from all eyes. Preoperatively, the horizontal axis was recorded in
      the marked group for use in manual cyclotorsional alignment prior to surgical
      iris registration. During iris registration, the preoperative iris information
      was compared to the eye-tracker captured image. The magnitudes of the
      registration error angle and cyclotorsional movement during the subsequent laser
      ablation were recorded and analyzed. RESULTS: Mean magnitude of registration
      error angle (absolute value) was 1.82 degrees +/-1.31 degrees  (range: 0.00
      degrees  to 5.50 degrees ) and 2.90 degrees +/-2.40 degrees  (range: 0.00 degrees
      to 13.50 degrees ) for the marked and unmarked groups, respectively (P<.001).
      Mean magnitude of cyclotorsional movement during the laser ablation (absolute
      value) was 1.15 degrees +/-1.34 degrees  (range: 0.00 degrees  to 7.00 degrees )
      and 0.68 degrees +/-0.97 degrees  (range: 0.00 degrees  to 6.00 degrees ) for the
      marked and unmarked groups, respectively (P=.005). Forty-six percent and 60% of
      eyes had registration error >2 degrees , whereas 22% and 20% of eyes had
      cyclotorsional movement during ablation >2 degrees  in the marked and unmarked
      groups, respectively. CONCLUSIONS: Limbal-marking-based manual alignment prior to
      laser ablation significantly reduced cyclotorsional registration error. However,
      residual registration misalignment and cyclotorsional movements remained during
      ablation.

PMID- 22421094
TI  - Effect of simulated IOL tilt and decentration on spherical aberration after
      hyperopic LASIK for different intraocular lenses.
AB  - PURPOSE: To evaluate visual quality differences among intraocular lenses (IOLs)
      in patients with previous hyperopic laser ablations and to assess the impact of
      decentration and tilt of IOLs on visual quality. METHODS: An adaptive optics
      visual simulator was used to simulate the wavefront aberration pattern of one
      aberration-correcting IOL (AcrySof IQ SN60WF, Alcon Laboratories Inc) and two
      spherical IOLs with different amounts of positive spherical aberration (Akreos
      Adapt [Bausch & Lomb] and Triplato [AJL Ophthalmic]) in five situations-centered,
      0.2 mm and 0.4 mm of decentration, and 2 degrees  and 4 degrees  of tilt-in two
      groups: simulated low hyperopic laser corneal ablation (low hyperopia group) and
      high hyperopic laser corneal ablation (high hyperopia group). Monocular distance
      visual acuity at 100%, 50%, and 10% contrast were measured. RESULTS: Ten eyes
      were evaluated. When the IOLs were centered, all IOLs obtained comparable results
      for the low hyperopia group, whereas for the high hyperopia group, the Akreos
      Adapt and AcrySof IQ SN60WF showed better visual acuity than the Triplato. When
      the IOLs were misaligned, for the low hyperopia group, the best visual acuity
      results were obtained with the Akreos Adapt and the most critical situation was
      at 0.4 mm of decentration. For the high hyperopia group, misalignments decreased
      visual acuity in a higher amount than for the low hyperopia group. CONCLUSIONS:
      Our results suggest that the IOLs studied offer good visual quality when they are
      centered for both groups. However, tilt and decentration of monofocal IOLs have
      an impact on visual function in patients with hyperopic ablations. For these
      patients, the Akreos Adapt is the most robust to misalignments.

PMID- 22421095
TI  - Aspergillus endophthalmitis in one eye subsequent to bilateral anterior chamber
      phakic intraocular lens implantation.
AB  - PURPOSE: To present a case of unilateral Aspergillus endophthalmitis after
      bilateral anterior chamber phakic intraocular lens (IOL) implantation in a 26
      year-old myopic patient. METHODS: Three days after bilateral phakic IOL
      implantation, the patient presented with complaints of pain and low vision in the
      left eye and was treated for uveitis. Four weeks later, the patient presented
      with complaints of pain and decreased vision. RESULTS: Culture results of the
      anterior chamber and IOL specimens were positive for Aspergillus. Anterior
      chamber washing, membrane removal, anterior chamber phakic IOL removal,
      lensectomy, and anterior vitrectomy along with administration of topical,
      systemic, and antifungal drugs and intracameral tissue plasminogen activator
      improved the patient's corrected distance visual acuity to 20/40 with +6.00 -2.00
      * 130 degrees . CONCLUSIONS: Although ocular inflammation occurring after IOL
      implantation responds to corticosteroids, intraocular infections should always be
      taken into consideration to prevent severe ocular morbidity.

PMID- 22421096
TI  - A sexual health program for Vietnamese parents of adolescents: a preliminary
      report on changes in parental knowledge, communication, and self-efficacy for
      condom use.

PMID- 22421097
TI  - Alcohol and adherence to antiretroviral medications: interactive toxicity beliefs
      among people living with HIV.
AB  - When taken without interruption, antiretroviral therapies (ART) effectively treat
      HIV infection. Alcohol is a well-known direct and indirect influence on ART
      adherence. Believing that drinking is harmful while taking ART (interactive
      toxicity beliefs) is also associated with poor adherence. The current study
      included 333 people living with HIV who were taking ART and actively using
      alcohol. Participants were recruited from health care providers and social
      services in a major southern U.S. city. Results showed that 52% of persons found
      non-adherent to ART stated that they stopped taking their medications when they
      were drinking. Multivariate analyses showed that interrupting treatment when
      drinking was related to current non-adherence, over and above several common
      correlates of non-adherence including frequency of alcohol use itself. These
      results confirm and extend past research, indicating an urgent need for
      medication adherence interventions designed for people living with HIV who drink.

PMID- 22421098
TI  - Blood clot obstruction of the jejunojejunostomy after laparoscopic gastric
      bypass.
AB  - BACKGROUND: Acute jejunojejunostomy (JJ) obstruction after laparoscopic gastric
      bypass secondary to the formation of an intraluminal blood clot is a rare event.
      We analyzed our experience with such complications from a large consecutive
      patient series at a university hospital that is a referral center for bariatric
      surgery. METHODS: A retrospective review of patient data in a register of all
      patients who had undergone gastric bypass from June 2004 to March 2011 was
      performed. Reoperations were analyzed for the cause and findings. The patients
      received routine postoperative administration of low-molecular-weight heparin.
      RESULTS: Of 1066 patients, 5 (.5%; 4 women and 1 man), who had undergone
      laparoscopic gastric bypass, with a median body mass index of 42 kg/m(2) (range
      40-46), underwent reoperation for obstruction of the JJ secondary to a blood
      clot. The indications for reoperation were signs of bleeding, nausea, or findings
      on abdominal computed tomography. The time of reoperation was 1, 1, 2, 3, and 11
      days after the primary procedure. All patients underwent reoperation by
      laparoscopy, with evacuation of the blood clot through an opening of the suture
      or staple lines without additional revision of the JJ. The gastric remnant was
      decompressed using a percutaneously placed gastrostomy tube. One patient had
      gastric leakage from the staple lines (blowout) that necessitated several later
      revisions for subcutaneous abscesses. Another patient developed acute
      pancreatitis. CONCLUSION: Blood clots can cause early obstruction of the JJ after
      gastric bypass. Awareness of this potentially rapidly progressive and life
      threatening complication will allow immediate intervention and reduce the risk of
      serious sequelae.

PMID- 22421099
TI  - An intrinsically compliant robotic orthosis for treadmill training.
AB  - A new intrinsically compliant robotic orthosis powered by pneumatic muscle
      actuators (PMA) was developed for treadmill training of neurologically impaired
      subjects. The robotic orthosis has hip and knee sagittal plane rotations actuated
      by antagonistic configuration of PMA. The orthosis has passive mechanisms to
      allow vertical and lateral translations of the trunk and a passive hip
      abduction/adduction joint. A foot lifter having a passive spring mechanism was
      used to ensure sufficient foot clearance during swing phase. A trajectory
      tracking controller was implemented to evaluate the performance of the robotic
      orthosis on a healthy subject. The results show that the robotic orthosis is able
      to perform the treadmill training task by providing sufficient torques to achieve
      physiological gait patterns and a realistic stepping experience. The orthosis is
      a new addition to the rapidly advancing field of robotic orthoses for treadmill
      training.

PMID- 22421100
TI  - Dependence of gold nanoparticle production on pulse duration by laser ablation in
      liquid media.
AB  - The dependence on laser fluence and laser pulse duration of size, size
      distribution and concentration of gold nanoparticles synthesized by laser
      ablation in liquid media was investigated. It was demonstrated that increasing
      laser energy from 1 to 5 mJ/pulse enhances the ablation rate by a factor of 100.
      The behavior of the ablation rate, hence of the nanoparticle concentration, as a
      function of pulse duration (varied from 40 fs to 200 ps) was found to strongly
      differ from that in air, which can be explained by photoionization and important
      losses of laser energy in the femtosecond regime. The optimal pulse duration for
      maximum ablation rate in liquid media was found to be equal to 2 ps.

PMID- 22421101
TI  - Characterization of the "sporadically lurking HAP1-immunoreactive (SLH) cells" in
      the hippocampus, with special reference to the expression of steroid receptors,
      GABA, and progenitor cell markers.
AB  - Huntingtin-associated protein 1 (HAP1) is a neural huntingtin interactor that is
      widely expressed as a core molecule of the stigmoid body (a neurocytoplasmic
      inclusion) in the limbic and hypothalamic regions and has putative protective
      functions against some neurodegenerative diseases (HAP1 protection hypothesis).
      Although HAP1 has been reported to be intimately associated with several steroid
      receptors, HAP1-immunoreactive (HAP1-ir) cells remain to be identified in the
      hippocampus, which is one of the major steroidal targets. In this study, we
      determined the distribution of hippocampal HAP1-ir cells in light and
      fluorescence microscopy and characterized their morphological relationships with
      steroid receptors, markers of adult neurogenesis, and the GABAergic system in
      adult male and female Wistar rats. HAP1-ir cells, which were sporadically
      distributed particularly in the subgranular zone (SGZ) of the dentate gyrus and
      in the interface between the stratum lacunosum-moleculare and stratum radiatum of
      Ammon's horn, were identified as the "sporadically lurking HAP1-ir (SLH)" cells.
      The SLH cells showed no clear association with neural progenitor/proliferating or
      migrating cell markers of adult neurogenesis, such as Ki-67, proliferating cell
      nuclear antigen, doublecortin, and glial fibrillary acidic protein in the SGZ,
      whereas all the SLH cells expressed a neuronal specific nuclear protein (NeuN).
      More than 90% of the SLH cells expressed nuclear estrogen receptor (ER) alpha but
      neither ERbeta nor the androgen receptor, whereas glucocorticoid receptor was
      differently stained in the SLH cells depending on the antibodies. More than 60%
      of them exhibited GABA immunoreactivity in the SGZ, suggestive of basket cells,
      but they were distinct from the ones expressing cholecystokinin or parvalbumin.
      We conclude that SLH cells, which should be stable against apoptosis due to
      putative HAP1 protectivity, might be involved in estrogen-dependent maturation,
      remodeling and activation of hippocampal memory and learning functions via
      ERalpha and partly through GABAergic regulation.

PMID- 22421102
TI  - Effects of age and walking speed on long-range autocorrelations and fluctuation
      magnitude of stride duration.
AB  - Stride duration variability is considered a marker of gait balance and can be
      investigated in at least two different ways. Fluctuation magnitude can be
      addressed by classical mathematical methods, whereas fluctuation dynamics between
      strides can be characterized using the autocorrelation function. Although each
      approach has revealed changes of these parameters in different age-groups, most
      studies have focused on spontaneous walking speeds, which vary across groups and
      is described as a possible confounder in the assessment of stride duration
      variability. In the present study, the influence of speed on stride duration
      fluctuations was first analyzed in six young adults walking at six different
      speeds on a treadmill. Second, the results of 18 subjects from three different
      age-groups (~5, 25, and 75 years old) were compared to assess the effect of age
      on the same variables at three different speeds. Fluctuation dynamics was
      evaluated, thanks to combined mathematical methods recently validated in the
      context of physiological time series, to increase the level of confidence in the
      results. Fluctuation magnitude was assessed by coefficients of variation (CV) on
      the same and large number of 512 gait strides, to enhance the validity of
      comparisons between both parameters. Long-range autocorrelations were highlighted
      in all time series, and characteristics were not influenced by gait speed and age
      of the participants. This suggests that the dynamics of variability is efficient
      for comparing subjects presenting with different spontaneous speed, and supports
      the hypothesis that long-range variability of human gait reflects a centrally
      controlled behavior. In contrast, CV was inversely related to walking speed and
      the age of the subjects. Slower speeds increased CV values, and fluctuation
      magnitude was also significantly larger for children compared with young and old
      adults. This confirms that fluctuation magnitude and dynamics could be
      complementary tools for more complete gait characterization.

PMID- 22421103
TI  - Lead intoxication induces noradrenaline depletion, motor nonmotor disabilities,
      and changes in the firing pattern of subthalamic nucleus neurons.
AB  - Lead intoxication has been suggested as a high risk factor for the development of
      Parkinson disease. However, its impact on motor and nonmotor functions and the
      mechanism by which it can be involved in the disease are still unclear. In the
      present study, we studied the effects of lead intoxication on the following: (1)
      locomotor activity using an open field actimeter and motor coordination using the
      rotarod test, (2) anxiety behavior using the elevated plus maze, (3) "depression
      like" behavior using sucrose preference test, and (4) subthalamic nucleus (STN)
      neuronal activity using extracellular single unit recordings. Male Sprague-Dawley
      rats were treated once a day with lead acetate or sodium acetate (20 mg/kg/d
      i.p.) during 3 weeks. The tissue content of monoamines was used to determine
      alteration of these systems at the end of experiments. Results show that lead
      significantly reduced exploratory activity, locomotor activity and the time spent
      on the rotarod bar. Furthermore, lead induced anxiety but not "depressive-like"
      behavior. The electrophysiological results show that lead altered the discharge
      pattern of STN neurons with an increase in the number of bursting and irregular
      cells without affecting the firing rate. Moreover, lead intoxication resulted in
      a decrease of tissue noradrenaline content without any change in the levels of
      dopamine and serotonin. Together, these results show for the first time that lead
      intoxication resulted in motor and nonmotor behavioral changes paralleled by
      noradrenaline depletion and changes in the firing activity of STN neurons,
      providing evidence consistent with the induction of atypical parkinsonian-like
      deficits.

PMID- 22421104
TI  - Effect of nonylphenol on male reproduction: analysis of rat epididymal
      biochemical markers and antioxidant defense enzymes.
AB  - The mechanism by which nonylphenol (NP) interferes with male reproduction is not
      fully elucidated. Therefore, the present study was conducted to evaluate the
      effect of NP on male reproductive organ's weight, sperm characteristics, and to
      elucidate the nature and mechanism of action of NP on the epididymis. Adult male
      Wistar rats were gavaged with NP, dissolved in corn oil, at 0, 100, 200 or
      300mg/kg/day for 30 consecutive days. Control rats were gavaged with vehicle
      (corn oil) alone. Body weight did not show any significant change while, absolute
      testes and epididymides weights were significantly decreased. Sperm count in
      cauda and caput/corpus epididymides, and sperm motility was significantly
      decreased. Daily sperm production was significantly decreased in a dose-related
      manner. Sperm transit time in cauda epididymis was significantly decreased by
      300mg/kg, while in the caput/corpus epididymis it was significantly decreased by
      200 and 300mg/kg of NP. Plasma LDH was significantly increased while; plasma
      testosterone was significantly decreased in a dose-related pattern. In the
      epididymal sperm, NP decreased acrosome integrity, Deltapsim and 5'-nucleotidase
      activity. Hydrogen peroxide (H(2)O(2)) production and LPO were significantly
      increased in a dose-related pattern. The activities of SOD, CAT and GPx were
      significantly decreased in the epididymal sperm. In conclusion, this study
      revealed that NP treatment impairs spermatogenesis and has a cytotoxic effect on
      epididymal sperm. It disrupts the prooxidant and antioxidant balance. This leads
      oxidative stress in epididymal sperms of rat. Moreover, the reduction in sperm
      transit time may affect sperm quality and fertility potential.

PMID- 22421105
TI  - Photosynthetic electron flow to oxygen and diffusion of hydrogen peroxide through
      the chloroplast envelope via aquaporins.
AB  - Light-induced generation of superoxide radicals and hydrogen peroxide in isolated
      thylakoids has been studied with a lipophilic spin probe, cyclic hydroxylamine 1
      hydroxy-4-isobutyramido-2,2,6,6-tetramethylpiperidinium (TMT-H) to detect
      superoxide radicals, and the spin trap alpha-(4-pyridyl-1-oxide)-N-tert
      butylnitron (4-POBN) to detect hydrogen peroxide-derived hydroxyl radicals.
      Accumulation of the radical products of the above reactions has been followed
      using electron paramagnetic resonance. It is found that the increased production
      of superoxide radicals and hydrogen peroxide in higher light is due to the
      enhanced production of these species within the thylakoid membrane, rather than
      outside the membrane. Fluorescent probe Amplex red, which forms fluorescent
      product, resorufin, in the reaction with hydrogen peroxide, has been used to
      detect hydrogen peroxide outside isolated chloroplasts using confocal microscopy.
      Resorufin fluorescence outside the chloroplasts is found to be suppressed by 60%
      in the presence of the inhibitor of aquaporins, acetazolamide (AZA), indicating
      that hydrogen peroxide can diffuse through the chloroplast envelope aquaporins.
      It is demonstrated that AZA also inhibits carbonic anhydrase activity of the
      isolated envelope. We put forward a hypothesis that carbonic anhydrase presumably
      can be attached to the envelope aquaporins. This article is part of a Special
      Issue entitled: Photosynthesis Research for Sustainability: from Natural to
      Artificial.

PMID- 22421106
TI  - Platelet and endothelial expression of clotting factors for the treatment of
      hemophilia.
AB  - Hemostasis is achieved by the coordinate interaction of plasma, platelets, and
      vascular endothelium. Coagulation factors circulate in plasma with synthesis in
      liver and in endothelium. Interaction between Factor VIII (FVIII) and von
      Willebrand factor (VWF) in plasma is critically important, but there remains some
      question about whether this relationship is first established within the
      endothelial cell or in plasma. When FVIII is expressed with VWF in a cell that
      stores VWF, FVIII will also be stored and released. The manuscript will summarize
      some studies in which gene therapy exploits this relationship between VWF and
      FVIII to achieve hemostasis even in the presence of circulating inhibitory
      antibodies to FVIII. VWF is critical to this efficacy in the presence of
      inhibitors. Since FIX expression in platelets is effective for hemophilia B,
      efficacy in the presence of inhibitory antibodies to FIX was not achieved and
      emphasized the importance of VWF to the efficacy of platelet FVIII expression.
      These approaches have been studied in murine models but will need further study
      before this approach can be attempted clinically.

PMID- 22421107
TI  - The G534E-polymorphism of the gene encoding the factor VII-activating protease is
      a risk factor for venous thrombosis and recurrent events.
AB  - INTRODUCTION: A single nucleotide polymorphism of the factor VII activating
      protease (FSAP), FSAP Marburg I (rs7080536) has been identified as a risk factor
      for venous thrombosis, but its clinical role has so far been controversial in
      part due to small cohort sizes. The aim of the present case-control study was to
      elucidate the impact of the FSAP Marburg I polymorphism (FSAP-MI) on the
      development of venous thromboembolic disease (VTE) with other known sequence
      variations, including Factor V Leiden (rs6025) and Factor II G20210A (rs1799963).
      MATERIALS AND METHODS: The study included 891 patients (312 male and 579 female)
      with a history of deep venous thrombosis (DVT) and/or pulmonary embolism (PE) and
      1283 healthy blood donors with no history of venous thromboembolic disease.
      RESULTS: We found that besides to the well-established aforementioned sequence
      variations of FV and Prothrombin, the FSAP Marburg I (FSAP-MI) polymorphism was
      significantly associated with the development of DVTs (1.65 (1.16-2.34) OR (95%
      CI)) and recurrent thromboembolic events (DVT and PE) (2.13 (1.35-3.36) OR (95%
      CI)). Comparing patients displaying one or more events FSAP-MI was still
      associated with the development of recurrent thromboembolic events (1.64 (1-
      2.69) OR (95% CI)). CONCLUSIONS: We conclude that FSAP Marburg-I genotyping may
      be used to determine the risk for thromboembolic disorders in patients with
      suspected thrombophilia and known DVT or PE.

PMID- 22421108
TI  - Phenotyping of circulating CD8+ T cell subsets in human cutaneous leishmaniasis.
AB  - Recovery from CL is usually accompanied with long-lasting protection and
      induction of strong immune response. The phenotypes, generation and maintenance
      of central (=T(CM)) and effector (=T(EM)) memory T cell subsets in human
      leishmaniasis are not well known. Profile of T cell subsets were analyzed on
      peripheral CD8+ T cells from volunteers with history of cutaneous leishmaniasis
      (HCL). In HCL and control groups, mean frequencies of CCR7+CD45RA+CD8+ naive and
      CCR7-CD45RA-CD8+ T(EM) cells were higher than other subsets before culture, but
      after stimulation with soluble Leishmania antigen, the frequency of naive T cells
      was significantly decreased and the frequency of T(EM) cells was significantly
      increased. T(EM) phenotype composed the highest portion of proliferating Carboxy
      Fluorescein diacetate Succinimidyl Ester (CFSE)-dim population which was
      significantly higher in HCL volunteers than in control group. Stimulation of
      isolated CD8+ memory T cells, but not naive T cells, from HCL volunteers induced
      a significantly higher IFN-gamma production compared with that of healthy
      controls. Intracellular IFN-gamma staining provided the same result. Memory
      population is shown to be responsible for Leishmania-induced IFN-gamma
      production. Leishmania-reactive proliferating T(EM) cells were identified as the
      most frequent subset which may play a role in recall immune response and
      protection against Leishmania infection.

PMID- 22421109
TI  - Effect of quercetin on Vibrio cholerae induced nuclear factor-kappaB activation
      and interleukin-8 expression in intestinal epithelial cells.
AB  - Vibrio cholerae, the etiological agent of cholera, colonizes the small intestine,
      produces an enterotoxin and causes acute inflammatory response at intestinal
      epithelial cell surface. Pretreatment of intestinal epithelial cells with
      quercetin reduces the level of V. cholerae induced IL-8 in dose and time
      dependent manner as determined by ELISA and RT-PCR. Immunofluorescence studies
      showed that quercetin suppresses the translocation of p50 subunit of NF-kappaB.
      In vivo, quercetin administration produced a significant reduction of neutrophil
      infiltration in the intestinal epithelial layer of suckling mouse. Taken
      together, quercetin could inhibit the V. cholerae induced inflammation and may
      therefore find use in management of V. cholerae induced pathogenesis.

PMID- 22421110
TI  - Mapping immunodominant antigens and H-2-linked antibody responses in mice
      urogenitally infected with Chlamydia muridarum.
AB  - To identify immunodominant antigens and MHC-restricted antibody responses, seven
      different strains of mice were intravaginally infected with Chlamydia muridarum
      and compared for antibody responses to 257 C. muridarum proteins. The 7 strains
      of mice recognized a total of 109 proteins as antigens, of which, 5 antigens
      (TC0660, TC0727, TC0828, TC0726 & TC0268) were each recognized by 60% or more
      mice from each mouse strain and thus designated as immunodominant antigens.
      Furthermore, antibody responses to 19 other antigens displayed strong
      associations with mouse H-2 haplotypes, including 6 antigens (TC0480, TC0912,
      TC0229, TCA04, TC0289 & TC0892) whose antibody responses were linked to H-2(b), 8
      (TC0035, TC0387, TC0052, TC0781, TC0373, TC0117, TC0066 & TC0396) to H-2(d) and 5
      (TC0512, TC0177, TC0589, TC0794 & TC0596) to H-2(k) haplotypes respectively.
      Interestingly, H-2(b) was negatively associated with antibody responses to most
      of the antigens that were positively linked to H-2(d) or H-2(k) haplotypes. These
      results by mapping Chlamydia trachomatis antigens commonly recognized by mice
      with different strain background and H-2 genes and revealing antigen association
      with H-2 haplotypes have provided important information for developing chlamydial
      subunit vaccines and understanding chlamydial pathogenesis.

PMID- 22421111
TI  - Characterization of atypical Enteropathogenic Escherichia coli (aEPEC) isolated
      from dogs.
AB  - Enteropathogenic Escherichia coli (EPEC), an important human pathogen has the
      ability to form attaching and effacing lesions on the intestinal epithelium and
      has been isolated from a wide range of species. Two EPEC subgroups are
      recognized: typical (tEPEC) and atypical (aEPEC) strains, differing by the
      presence of EAF plasmid and bundle-forming pilus (BFP) in typical strains and
      their absence in atypical strains. This study searched the presence of EPEC
      strains in 101 fecal samples of diarrheic (n=65) and non-diarrheic (n=36) dogs
      from two cities in Rio de Janeiro State, Brazil. The isolates were evaluated for
      the presence of eae, tir, espA, espB and bfpA genes, EAF plasmid, and for the
      insertion site of the LEE locus. Cell-adherence assays, fluorescent actin
      staining (FAS) test, hemolysin production and serotyping were also performed.
      Twenty eight aEPEC isolates were recovered from 48 eae-positive fecal samples, 24
      from diarrheic animals and 4 from non-diarrheic ones. PCR showed that most
      isolates was positive for beta or gamma intimin, and for beta or alpha subtypes
      of tir, espA and espB. Six isolates showed a selC insertion of locus LEE. Only
      two isolates from the same diarrheic animal harbored the bfpA gene, and none
      presented the EAF plasmid. Most isolates was FAS-positive and showed a localized
      adherence-like (LAL) in a 6h HeLa cell-adherence assay. A wide diversity of
      serotypes was detected including O4:H16 and O51:H40, previously described in
      human disease. The phenotypic and genotypic markers of aEPEC isolated from
      diarrheic and non-diarrheic dogs were similar to those found in isolates
      recovered from human disease.

PMID- 22421112
TI  - [Glycemic control at hospital: why does it not improve? ].

PMID- 22421113
TI  - Ethical dilemmas in the management of tumor-stage mycosis fungoides in a pregnant
      patient.

PMID- 22421114
TI  - Utilizing hairdressers for early detection of head and neck melanoma: an untapped
      resource.
AB  - This commentary raises an important issue that has not been sincerely considered
      in the field of dermatology, which is the vital role of hairdressers--a group
      that makes daily observations of the general populations' scalp and neck--in the
      detection of head and neck melanomas in the general population. We note several
      key areas of research that are needed to assess the feasibility of using
      hairdressers as a resource for melanoma detection and referral. If research
      suggests hairdressers can be trained and are willing to make appropriate
      referrals then implementing these efforts will likely reduce the increasing
      disease burden of head and neck melanomas.

PMID- 22421115
TI  - Response to the letter to editor re: "Methotrexate and psoriasis: consensus
      conference".

PMID- 22421117
TI  - Diagnostic usefulness of dermatoscopy in differentiating lichen sclerous et
      atrophicus from morphea.

PMID- 22421118
TI  - Two-year assessment of effect of topical corticosteroids on bone mineral density
      in adults with moderate to severe atopic dermatitis.

PMID- 22421119
TI  - The relative popularity of nonprocedural dermatology fellowships.

PMID- 22421120
TI  - Squamous cell carcinoma complicating discoid lupus erythematosus in Chinese
      patients: review of the literature, 1964-2010.

PMID- 22421121
TI  - Applying for dermatology residency is difficult and expensive.

PMID- 22421122
TI  - Vulvar melanoma: a missed opportunity for early intervention?

PMID- 22421123
TI  - Graft-versus-host disease: part I. Pathogenesis and clinical manifestations of
      graft-versus-host disease.
AB  - Approximately 25,000 allogeneic hematopoietic cell transplants are performed
      worldwide each year for a variety of malignant and non-malignant conditions.
      Graft-versus-host disease represents one of the most frequent complications and
      is a major source of long-term morbidity and mortality. Whereas acute graft
      versus-host disease is induced by recognition of host tissues as foreign by
      immunocompetent donor cells, the pathogenesis of chronic graft-versus-host
      disease is not as well understood, and continues to be a major treatment
      challenge. Part I of this two-part series reviews the epidemiologic factors,
      classification, pathogenesis, and clinical manifestations of acute and chronic
      graft-versus-host disease. Part II discusses the topical, physical, and systemic
      treatment options available to patients with graft-versus-host disease.

PMID- 22421124
TI  - Graft-versus-host disease: part II. Management of cutaneous graft-versus-host
      disease.
AB  - Dermatologists are ideally suited to manage the various cutaneous sequelae of
      graft-versus-host disease (GVHD) outlined in part I of this review. However, the
      complexity of the patient with GVHD, including comorbidities, potential drug
      interactions related to polypharmacy, and the lack of evidence-based treatment
      guidelines, are significant challenges to optimizing patient care. In this
      section, we will provide an outline for the role of the dermatologist in a
      multispecialty approach to caring for patients with GVHD.

PMID- 22421127
TI  - Panniculitis in alpha-1 antitrypsin deficiency treated with enzyme replacement.

PMID- 22421128
TI  - Transfusion-associated graft-versus-host disease: a case report and review of
      literature.

PMID- 22421129
TI  - Dermatoscopy of early-onset necrobiosis lipoidica.

PMID- 22421130
TI  - Automatic localization of solid organs on 3D CT images by a collaborative
      majority voting decision based on ensemble learning.
AB  - PURPOSE: Organ segmentation is an essential step in the development of computer
      aided diagnosis/surgery systems based on computed tomography (CT) images. A
      universal segmentation approach/scheme that can adapt to different organ
      segmentations can substantially increase the efficiency and robustness of such
      computer-aided systems. However, this is a very challenging problem. An initial
      determination of the approximate position and range of a target organ in CT
      images is prerequisite for precise organ segmentations. In this study, we have
      proposed a universal approach that enables automatic localization of the
      approximate position and range of different solid organs in the torso region on
      three-dimensional (3D) CT scans. METHODS: The location of a target organ in a 3D
      CT scan is presented as a 3D rectangle that bounds the organ region tightly and
      accurately. Our goal was to automatically and effectively detect such a target
      organ-specific 3D rectangle. In our proposed approach, multiple 2D detectors are
      trained using ensemble learning and their outputs are combined using a
      collaborative majority voting in 3D to accomplish the robust organ localizations.
      RESULTS: We applied this approach to localize the heart, liver, spleen, left
      kidney, and right-kidney regions independently using a CT image database that
      includes 660 torso CT scans. In the experiment, we manually labeled the
      abovementioned target organs from 101 3D CT scans as training samples and used
      our proposed approach to localize the 5 kinds of target organs separately on the
      remaining 559 torso CT scans. The localization results of each organ were
      evaluated quantitatively by comparing with the corresponding ground truths
      obtained from the target organs that were manually labeled by human operators.
      Experimental results showed that success rates of such organ localizations were
      distributed from 99% to 75% of the 559 test CT scans. We compared the performance
      of our approach with an atlas-based approach. The errors of the detected organ
      center-positions in the successful CT scans by our approach had a mean value of
      5.14 voxels, and those errors were much smaller than the results (mean value
      about 25 voxels) from the atlas-based approach. The potential usefulness of the
      proposed organ localization was also shown in a preliminary investigation of left
      kidney segmentation in non-contrast CT images. CONCLUSIONS: We proposed an
      approach to accomplish automatic localizations of major solid organs on torso CT
      scans. The accuracy of localizations, flexibility of localizations of different
      organs, robustness to contrast and non-contrast CT images, and normal and
      abnormal patient cases, and computing efficiency were validated on the basis of a
      large number of torso CT scans.

PMID- 22421131
TI  - Segmentation of retinal vessels with a hysteresis binary-classification paradigm.
AB  - Vessel segmentation in photographies of the retina is needed in a set of computer
      supported medical applications related to diagnosis and surgery planning.
      Considering each pixel in an image as a point in a feature space, segmentation is
      a binary classification problem where pixels need to be assigned to one of two
      classes: object and background. We describe a paradigm of hysteresis-classifier
      design that we apply to the problem of vessel segmentation. Before
      classification, a multidimensional feature vector is computed for each pixel,
      such that in the corresponding feature space, vessels and background are more
      separable than in the original image space. Several classifiers that stem from
      the hysteresis-classifier design paradigm are tested with this feature space on
      publicly available databases. These classifiers are very fast and achieve results
      that are comparable or even superior to known dedicated methods. Hysteresis-based
      classifiers represent a fast and accurate solution for the retinal-vessel
      segmentation problem.

PMID- 22421132
TI  - Therapeutic hypothermia after return of spontaneous circulation: should be
      offered to all?

PMID- 22421133
TI  - Magnetically sensitive light-induced reactions in cryptochrome are consistent
      with its proposed role as a magnetoreceptor.
AB  - Among the biological phenomena that fall within the emerging field of "quantum
      biology" is the suggestion that magnetically sensitive chemical reactions are
      responsible for the magnetic compass of migratory birds. It has been proposed
      that transient radical pairs are formed by photo-induced electron transfer
      reactions in cryptochrome proteins and that their coherent spin dynamics are
      influenced by the geomagnetic field leading to changes in the quantum yield of
      the signaling state of the protein. Despite a variety of supporting evidence, it
      is still not clear whether cryptochromes have the properties required to respond
      to magnetic interactions orders of magnitude weaker than the thermal energy,
      k(B)T. Here we demonstrate that the kinetics and quantum yields of photo-induced
      flavin-tryptophan radical pairs in cryptochrome are indeed magnetically
      sensitive. The mechanistic origin of the magnetic field effect is clarified, its
      dependence on the strength of the magnetic field measured, and the rates of
      relevant spin-dependent, spin-independent, and spin-decoherence processes
      determined. We argue that cryptochrome is fit for purpose as a chemical
      magnetoreceptor.

PMID- 22421134
TI  - Antigen-specific antibody responses in B-1a and their relationship to natural
      immunity.
AB  - B-1a cells are primarily thought of as natural antibody-producing cells. However,
      we now show that appropriate antigenic stimulation induces IgM and IgG B-1a
      antibody responses and long-lived T-independent antigen-specific B-1a memory that
      differs markedly from canonical B-2 humoral immunity. Thus, we show here that in
      the absence of inflammation, priming with glycolipid (FtL) from Francisella
      tularensis live vaccine strain induces splenic FtL-specific B-1a to mount
      dominant IgM and activation-induced cytidine deaminase-dependent IgG anti-FtL
      responses that occur within 3-5 d of FtL priming and fade within 1 wk to natural
      antibody levels that persist indefinitely in the absence of secondary FtL
      immunization. Equally surprising, FtL priming elicits long-term FtL-specific B-1a
      memory cells (IgM>>IgG) that migrate rapidly to the peritoneal cavity and persist
      there indefinitely, ready to respond to appropriately administrated secondary
      antigenic stimulation. Unlike B-2 responses, primary FtL-specific B-1a responses
      and establishment of persistent FtL-specific B-1a memory occur readily in the
      absence of adjuvants, IL-7, T cells, or germinal center support. However, in
      another marked departure from the mechanisms controlling B-2 memory responses,
      rechallenge with FtL in an inflammatory context is required to induce B-1a
      secondary antibody responses. These findings introduce previously unexplored
      vaccination strategies for pathogens that target the B-1a repertoire.

PMID- 22421135
TI  - Antigen-specific memory in B-1a and its relationship to natural immunity.
AB  - In the companion article by Yang and colleagues [Yang Y, et al. (2012) Proc Natl
      Acad Sci USA, 109, 10.1073/pnas.1121631109], we have shown that priming with
      glycolipid (FtL) from Francisella tularensis live-vaccine strain (i) induces FtL
      specific B-1a to produce robust primary responses (IgM >>IgG); (ii) establishes
      persistent long-term production of serum IgM and IgG anti-FtL at natural antibody
      levels; and (iii) elicits FtL-specific B-1a memory cells that arise in spleen but
      rapidly migrate to the peritoneal cavity, where they persist indefinitely but
      divide only rarely. Here, we show that FtL rechallenge alone induces these PerC B
      1a memory cells to divide extensively and to express a unique activation
      signature. However, FtL rechallenge in the context of a Toll-like receptor 4
      agonist-stimulated inflammatory response readily induces these memory cells to
      migrate to spleen and initiate production of dominant IgM anti-FtL secondary
      responses. Thus, studies here reveal unique mechanisms that govern B-1a memory
      development and expression, and introduce B-1a memory as an active participant in
      immune defenses. In addition, at a practical level, these studies suggest
      previously unexplored vaccination strategies for pathogen-associated antigens
      that target the B-1a repertoire.

PMID- 22421136
TI  - Whole lifespan microscopic observation of budding yeast aging through a
      microfluidic dissection platform.
AB  - Important insights into aging have been generated with the genetically tractable
      and short-lived budding yeast. However, it is still impossible today to
      continuously track cells by high-resolution microscopic imaging (e.g.,
      fluorescent imaging) throughout their entire lifespan. Instead, the field still
      needs to rely on a 50-y-old laborious and time-consuming method to assess the
      lifespan of yeast cells and to isolate differentially aged cells for microscopic
      snapshots via manual dissection of daughter cells from the larger mother cell.
      Here, we are unique in achieving continuous and high-resolution microscopic
      imaging of the entire replicative lifespan of single yeast cells. Our
      microfluidic dissection platform features an optically prealigned single focal
      plane and an integrated array of soft elastomer-based micropads, used together to
      allow for trapping of mother cells, removal of daughter cells, monitoring gradual
      changes in aging, and unprecedented microscopic imaging of the whole aging
      process. Using the platform, we found remarkable age-associated changes in
      phenotypes (e.g., that cells can show strikingly differential cell and vacuole
      morphologies at the moment of their deaths), indicating substantial heterogeneity
      in cell aging and death. We envision the microfluidic dissection platform to
      become a major tool in aging research.

PMID- 22421137
TI  - Crimean-Congo hemorrhagic fever virus nucleoprotein reveals endonuclease activity
      in bunyaviruses.
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV), a virus with high mortality in
      humans, is a member of the genus Nairovirus in the family Bunyaviridae, and is a
      causative agent of severe hemorrhagic fever (HF). It is classified as a biosafety
      level 4 pathogen and a potential bioterrorism agent due to its aerosol
      infectivity and its ability to cause HF outbreaks with high case fatality (~30%).
      However, little is known about the structural features and function of
      nucleoproteins (NPs) in the Bunyaviridae, especially in CCHFV. Here we report a
      2.3-A resolution crystal structure of the CCHFV nucleoprotein. The protein has a
      racket-shaped overall structure with distinct "head" and "stalk" domains and
      differs significantly with NPs reported so far from other negative-sense single
      stranded RNA viruses. Furthermore, CCHFV NP shows a distinct metal-dependent DNA
      specific endonuclease activity. Single residue mutations in the predicted active
      site resulted in a significant reduction in the observed endonuclease activity.
      Our results present a new folding mechanism and function for a negative-strand
      RNA virus nucleoprotein, extend our structural insight into bunyavirus NPs, and
      provide a potential target for antiviral drug development to treat CCHFV
      infection.

PMID- 22421139
TI  - Source of sugar nucleotides for starch and cellulose synthesis.

PMID- 22421138
TI  - Contextual encoding by ensembles of medial prefrontal cortex neurons.
AB  - Contextual representations serve to guide many aspects of behavior and influence
      the way stimuli or actions are encoded and interpreted. The medial prefrontal
      cortex (mPFC), including the anterior cingulate subregion, has been implicated in
      contextual encoding, yet the nature of contextual representations formed by the
      mPFC is unclear. Using multiple single-unit tetrode recordings in rats, we found
      that different activity patterns emerged in mPFC ensembles when animals moved
      between different environmental contexts. These differences in activity patterns
      were significantly larger than those observed for hippocampal ensembles. Whereas
      ~11% of mPFC cells consistently preferred one environment over the other across
      multiple exposures to the same environments, optimal decoding (prediction) of the
      environmental setting occurred when the activity of up to ~50% of all mPFC
      neurons was taken into account. On the other hand, population activity patterns
      were not identical upon repeated exposures to the very same environment. This was
      partly because the state of mPFC ensembles seemed to systematically shift with
      time, such that we could sometimes predict the change in ensemble state upon
      later reentry into one environment according to linear extrapolation from the
      time-dependent shifts observed during the first exposure. We also observed that
      many strongly action-selective mPFC neurons exhibited a significant degree of
      context-dependent modulation. These results highlight potential differences in
      contextual encoding schemes by the mPFC and hippocampus and suggest that the mPFC
      forms rich contextual representations that take into account not only sensory
      cues but also actions and time.

PMID- 22421140
TI  - An updated view on stem cell differentiation into smooth muscle cells.
AB  - Stem cells possess the ability of self-renewal and give rise to specific cell
      types. The differentiation of stem cells involves environmental factors,
      transduction of extra and intra-cellular signals, regulation of gene expression
      by transcriptional factors, microRNAs and chromosome structural modifiers.
      Vascular SMCs play a profound role in blood vessel physiology and participate in
      a number of cardiovascular diseases such as atherosclerosis, hypertension and
      restenosis. In addition, SMCs could be a crucial cell component for vascular
      tissue engineering. In this review, we aim to update the recent progress on the
      mechanisms of SMC differentiation from stem cells, which involve reactive oxygen
      species, epigenetic modifiers, transcription factors and microRNAs coordinately
      regulated during stem cell differentiation. We will also discuss the potential
      application of stem cell therapy for patients with cardiovascular diseases.

PMID- 22421141
TI  - CDC-25.1 controls the rate of germline mitotic cell cycle by counteracting WEE
      1.3 and by positively regulating CDK-1 in Caenorhabditis elegans.
AB  - In Caenorhabditis elegans, cdc-25.1 loss-of-function mutants display a lack of
      germline proliferation. We found that the proliferation defect of cdc-25.1
      mutants was suppressed by wee-1.3 RNAi. Further, among the seven cdk and seven
      cyclin homologs examined, cdk-1 and cyb-3 RNAi treatment caused the most severe
      germline proliferation defects in an rrf-1 mutant background, which were similar
      to those of the cdc-25.1 mutants. In addition, while RNAi of cyd-1 and cye-1
      caused significant germline proliferation defects, RNAi of cdk-2 and cdk-4 did
      not. Compared with the number of germ nuclei in wee-1.3(RNAi) worms, the number
      in wee-1.3(RNAi);cdk-1(RNAi) and wee-1.3(RNAi);cyb-3(RNAi) worms further
      decreased to the level of cdk-1(RNAi) and cyb-3(RNAi) worms, respectively,
      indicating that cdk-1 and cyb-3 are epistatic and function downstream of cdc-25.1
      and wee-1.3 in the control of the cell cycle. BrdU labeling of adult worms showed
      that, while 100% of the wild-type germ nuclei in the mitotic region incorporated
      BrdU when labeled for more than 12 h at 20 degrees C, a small fraction of the cdc
      25.1 mutant germ nuclei failed to incorporate BrdU even when labeled for 68 h.
      These results indicate that CDC-25.1 is required for maintaining proper rate of
      germline mitotic cell cycle. We propose that CDC-25.1 regulates the rate of
      germline mitotic cell cycle by counteracting WEE-1.3 and by positively
      controlling CDK-1, which forms a complex primarily with CYB-3, but also possibly
      with CYD-1 and CYE-1.

PMID- 22421143
TI  - The roles of REIC gene and its encoding product in gastric carcinoma.
AB  - REIC is downregulated in immortalized cell lines compared with the parental
      normal counterparts. It may inhibit colony formation, tumor growth and induce
      apoptosis. Here, gastric carcinoma or epithelial cells transfected with REIC
      expressing plasmid, its siRNA or treated with recombinant REIC were subjected to
      the phenotypes' measurement or related molecules' detection. REIC expression was
      examined in gastric carcinomas by RT-PCR, western blot and immunohistochemistry.
      REIC overexpression or treatment resulted in a low karyoplasmic ratio and
      proliferation, G1 arrest, high apoptosis, low migration, invasion or lamellipodia
      formation in AGS cells. REIC knockdown caused the opposite in GES-1 cells. Anti
      REIC antibody blocked the effects of REIC overexpression on proliferation, G1/S
      progression and apoptosis. Ectopic REIC expression downregulated the expression
      of beta-catenin, phosphorylated S6K (Thr389), phosphorylated Akt1/2/3 (Ser473),
      cyclin D2 and E, WAVE2 and upregulated phosphorylated mTOR (Ser2448) expression
      and the mRNA level of Akt1, Akt2, mTOR, Raptor and Rictor in AGS cells. REIC
      expression was negatively associated with tumor size, lymph node metastasis,
      dedifferentiation or poor prognosis of carcinoma. The serum REIC level was
      significantly higher in healthy individuals than the carcinoma patients and
      inversely linked to tumor size by ELISA. The possible mechanisms underlying the
      forced REIC overexpression or recombinant REIC mediated the reversal of the
      aggressive phenotypes of gastric carcinoma cells are to downregulate beta-catenin
      and WAVE2 expression and to alter other related target proteins. Downregulated
      REIC expression was closely linked to aggressive behaviors and poor prognosis of
      gastric carcinoma.

PMID- 22421142
TI  - Nutlin-3 induces apoptosis, disrupts viral latency and inhibits expression of
      angiopoietin-2 in Kaposi sarcoma tumor cells.
AB  - Kaposi sarcoma (KS) tumors often contain a wild-type p53. However, the function
      of this tumor suppressor in KS tumor cells is inhibited by both MDM2 and latent
      nuclear antigen (LANA) of Kaposi sarcoma-associated herpes virus (KSHV). Here, we
      report that MDM2 antagonist Nutlin-3 efficiently reactivates p53 in telomerase
      immortalized human umbilical vein endothelial cells (TIVE) that had been
      malignantly transformed by KSHV as well as in KS tumor cells. Reactivation of p53
      results in a G 1 cell cycle arrest, leading to inhibition of proliferation and
      apoptosis. Nutlin-3 inhibits the growth of "KS-like" tumors resulting from
      xenografted TIVE-KSHV cells in nude mice. In addition, Nutlin-3 strongly inhibits
      expression of the pro-angiogenic and pro-inflammatory cytokine angiopoietin-2
      (Ang-2). It also disrupts viral latency by inducing expression of KSHV lytic
      genes. These results suggest that Nutlin-3 might serve as a novel therapy for KS.

PMID- 22421144
TI  - Metformin suppresses growth of human head and neck squamous cell carcinoma via
      global inhibition of protein translation.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer in the
      world; the main risk factors are alcohol and tobacco use. Advancements in
      therapies have yet to improve the prognosis of HNSCC. The connection between
      diabetes and cancer is being recognized, and metformin has been shown to decrease
      cancer incidence in diabetic patients. Accordingly, here, for the first time, we
      investigated metformin's efficacy on the growth and viability of human HNSCC FaDU
      and Detroit cells. Our results show that metformin treatment (5-20 mM) dose
      dependently inhibits the growth of both cell lines. In FaDU cells, metformin
      caused 18-57% and 35-81% growth inhibition after 48 and 72 h treatments,
      respectively. Similarly, in Detroit 562 cells, 48 and 72 h metformin treatment
      resulted in 20-57% and 33-82% inhibition, respectively. Mechanistically,
      metformin caused G 1 arrest, which coincided with a decrease in the protein
      levels of CDKs (2, 4 and 6), cyclins (D1 and E) and CDK inhibitors (p15, p16, p18
      and p27), but no change in p19 and p21. Metformin also decreased the levels of
      oncogenic proteins Skp2 and beta-Trcp. In other studies, metformin decreased the
      phosphorylation of 4E-BP1 at Ser65, Thr37/46 and Thr70 sites, but drastically
      increased the phosphorylation of EF2 at Thr56 and AMPK at Thr172, which results
      in global translational inhibition. In summary, the observed wide spectrum of
      mechanistic effects of metformin on HNSCC cells provides support for the
      anticancer capability of the drug and its potential use in future therapies.

PMID- 22421145
TI  - The expanding proteome of the molecular chaperone HSP90.
AB  - The molecular chaperone HSP90 maintains the activity and stability of a diverse
      set of "client" proteins that play key roles in normal and disease biology.
      Around 20 HSP90 inhibitors that deplete the oncogenic clientele have entered
      clinical trials for cancer. However, the full extent of the HSP90-dependent
      proteome, which encompasses not only clients but also proteins modulated by
      downstream transcriptional responses, is still incompletely characterized and
      poorly understood. Earlier large-scale efforts to define the HSP90 proteome have
      been valuable but are incomplete because of limited technical sensitivity. Here
      we discuss previous large-scale surveys of proteome perturbations induced by
      HSP90 inhibitors in light of a significant new study using state-of-the-art SILAC
      technology combined with more sensitive high-resolution mass spectrometry (MS)
      that extends the catalog of proteomic changes in inhibitor-treated cancer cells.
      Among wide-ranging changes, major functional responses include downregulation of
      protein kinase activity and the DNA damage response alongside upregulation of the
      protein degradation machinery. Despite this improved proteomic coverage, there
      was surprisingly little overlap with previous studies. This may be due in part to
      technical issues but is likely also due to the variability of the HSP90 proteome
      with the inhibitor conditions used, the cancer cell type and the genetic status
      of client proteins. We suggest future proteomic studies to address these factors,
      to help distinguish client protein components from indirect transcriptional
      components and to address other key questions in fundamental and translational
      HSP90 research. Such studies should also reveal new biomarkers for patient
      selection and novel targets for therapeutic intervention.

PMID- 22421147
TI  - The role of telomere trimming in normal telomere length dynamics.
AB  - Telomeres consist of repetitive DNA and associated proteins that protect
      chromosome ends from illicit DNA repair. It is well known that telomeric DNA is
      progressively eroded during cell division, until telomeres become too short and
      the cell stops dividing. There is a second mode of telomere shortening, however,
      which is a regulated form of telomere rapid deletion (TRD) termed telomere
      trimming that is reviewed here. Telomere trimming appears to involve resolution
      of recombination intermediate structures, which shortens the telomere by release
      of extrachromosomal telomeric DNA. This has been detected in human and in mouse
      cells and occurs both in somatic and germline cells, where it sets an upper limit
      on telomere length and contributes to a length equilibrium set-point in cells
      that have a telomere elongation mechanism. Telomere trimming thus represents an
      additional mechanism of telomere length control that contributes to normal
      telomere dynamics and cell proliferative potential.

PMID- 22421146
TI  - Oncogene-induced senescence results in marked metabolic and bioenergetic
      alterations.
AB  - Oncogene-induced senescence (OIS) is characterized by permanent growth arrest and
      the acquisition of a secretory, pro-inflammatory state. Increasingly, OIS is
      viewed as an important barrier to tumorgenesis. Surprisingly, relatively little
      is known about the metabolic changes that accompany and therefore may contribute
      to OIS. Here, we have performed a metabolomic and bioenergetic analysis of Ras
      induced senescence. Profiling approximately 300 different intracellular
      metabolites reveals that cells that have undergone OIS develop a unique metabolic
      signature that differs markedly from cells undergoing replicative senescence. A
      number of lipid metabolites appear uniquely increased in OIS cells, including a
      marked increase in the level of certain intracellular long chain fatty acids.
      Functional studies reveal that this alteration in the metabolome reflects
      substantial changes in overall lipid metabolism. In particular, Ras-induced
      senescent cells manifest a decline in lipid synthesis and a significant increase
      in fatty acid oxidation. Increased fatty acid oxidation results in an
      unexpectedly high rate of basal oxygen consumption in cells that have undergone
      OIS. Pharmacological or genetic inhibition of carnitine palmitoyltransferase 1,
      the rate-limiting step in mitochondrial fatty acid oxidation, restores a pre
      senescent metabolic rate and, surprisingly, selectively inhibits the secretory,
      pro-inflammatory state that accompanies OIS. Thus, Ras-induced senescent cells
      demonstrate profound alterations in their metabolic and bioenergetic profiles,
      particularly with regards to the levels, synthesis and oxidation of free fatty
      acids. Furthermore, the inflammatory phenotype that accompanies OIS appears to be
      related to these underlying changes in cellular metabolism.

PMID- 22421148
TI  - MicroRNA-203 regulates caveolin-1 in breast tissue during caloric restriction.
AB  - Caloric restriction has been shown to increase lifespan in several organisms and
      to delay onset of age-related diseases. The transcriptional response to caloric
      restriction has been studied for mRNAs, while the microRNA signature following
      caloric restriction remains unexplored. Here, we characterize the microRNA
      expression in mouse breast tissue before and after caloric restriction, reporting
      several changes in the microRNA expression profile. In particular, miR-203 is
      found to be highly induced by caloric restriction, and we demonstrate that
      caveolin-1 as well as p63 are direct targets of miR-203 in vivo during caloric
      restriction. Using tissue culture models, we suggest that this regulation is
      important in both mouse and human. In conclusion, we show that the microRNA
      response induced by caloric restriction can regulate important factors in
      processes such as longevity and aging and is an integral and important component
      of the cellular response to caloric restriction.

PMID- 22421149
TI  - Pancreatic stellate cells form a niche for cancer stem cells and promote their
      self-renewal and invasiveness.
AB  - Chronic pancreatitis and pancreatic ductal adenocarcinoma (PDAC) are
      characterized by extensive fibrosis. Importantly, in PDAC, this results in poor
      vascularization and impaired drug delivery to the cancer cells. Therefore, the
      combined targeting of pancreatic tumor stroma and chemotherapy should enhance
      response rates, but the negative outcome of a recent phase III clinical trial for
      the combination of chemotherapy and hedgehog pathway inhibition suggests that
      other means also need to be considered. Emerging data indicate that elimination
      of cancer stem cells as the root of the cancer is of pivotal importance for
      efficient treatment of pancreatic cancer. Recently, we demonstrated in a highly
      relevant preclinical mouse model for primary pancreatic cancers that the
      combination of cancer stem cell-targeting strategies in combination with a stroma
      targeting agent, such as a hedgehog pathway inhibitor and chemotherapy, results
      in significantly enhanced long-term and progression-free survival. In the present
      study, we demonstrate mechanistically that Nodal-expressing pancreatic stellate
      cells are an important component of the tumor stroma for creating a paracrine
      niche for pancreatic cancer stem cells. Secretion of the embryonic morphogens
      Nodal/Activin by pancreatic stellate cells promoted in vitro sphere formation and
      invasiveness of pancreatic cancer stem cells in an Alk4-dependent manner. These
      data imply that the pancreatic cancer stem cell phenotype is promoted by
      paracrine Nodal/Activin signaling at the tumor-stroma interface. Therefore,
      targeting the tumor microenvironment is not only able to improve drug delivery
      but, even more importantly, destroys the cancer stem cell niche and, therefore,
      should be an integral part of cancer stem cell-based treatment strategies.

PMID- 22421150
TI  - Concerted epigenetic signatures inheritance at PcG targets through replication.
AB  - Polycomb group of proteins (PcG), by controlling gene silencing transcriptional
      programs through cell cycle, lock cell identity and memory. Recent chromatin
      genome-wide studies indicate that PcG targets sites are bivalent domains with
      overlapping repressive H3K27me3 and active H3K4me3 mark domains. During S phase,
      the stability of epigenetic signatures is challenged by the replication fork
      passage. Hence, specific mechanisms of epigenetic inheritance might be provided
      to preserve epigenome structures. Recently, we have identified a critical time
      window before replication, during which high levels of PcG binding and histone
      marks on BX-C PRE target sites set the stage for subsequent dilution of
      epigenomic components, allowing proper transmission of epigenetic signatures to
      the next generation. Here, we extended this analysis to promoter elements,
      showing the same mechanism of inheritance. Furthermore, to gain insight into the
      inheritance of PREs bivalent marks, we analyzed dynamics of H3K4me3 deposition, a
      mark that correlates with transcriptionally active chromatin. Likewise, we found
      an early S-phase enrichment of H3K4me3 mark preceding the replication-dependent
      dilution. This evidence suggests that all epigenetic marks are inherited
      simultaneously to ensure their correct propagation through replication and to
      protect the "bivalency" of PREs.

PMID- 22421151
TI  - The Rix1 (Ipi1p-2p-3p) complex is a critical determinant of DNA replication
      licensing independent of their roles in ribosome biogenesis.
AB  - Several replication-initiation proteins are assembled stepwise onto replicators
      to form pre-replicative complexes (pre-RCs) to license eukaryotic DNA
      replication. We performed a yeast functional proteomic screen and identified the
      Rix1 complex members (Ipi1p-Ipi2p/Rix1-Ipi3p) as pre-RC components and critical
      determinants of replication licensing and replication-initiation frequency. Ipi3p
      interacts with pre-RC proteins, binds chromatin predominantly at ARS sequences in
      a cell cycle-regulated and ORC- and Noc3p-dependent manner and is required for
      loading Cdc6p, Cdt1p and MCM onto chromatin to form pre-RC during the M-to-G1
      transition and for pre-RC maintenance in G1 phase-independent of its role in
      ribosome biogenesis. Moreover, Ipi1p and Ipi2p, but not other ribosome biogenesis
      proteins Rea1p and Utp1p, are also required for pre-RC formation and maintenance,
      and Ipi1p, -2p and -3p are interdependent for their chromatin association and
      function in pre-RC formation. These results establish a new framework for the
      hierarchy of pre-RC proteins, where the Ipi1p-2p-3p complex provides a critical
      link between ORC-Noc3p and Cdc6p-Cdt1p-MCM in replication licensing.

PMID- 22421152
TI  - Interplay between Hsp90 and TPR domain-containing proteins in steroidogenic
      signaling.

PMID- 22421153
TI  - Discordance between phosphorylation and recruitment of 53BP1 in response to DNA
      double-strand breaks.
AB  - During the DNA damage response (DDR), chromatin modifications contribute to
      localization of 53BP1 to sites of DNA double-strand breaks (DSBs). 53BP1 is
      phosphorylated during the DDR, but it is unclear whether phosphorylation is
      directly coupled to chromatin binding. In this study, we used human diploid
      fibroblasts and HCT116 tumor cells to study 53BP1 phosphorylation at Serine-25
      and Serine-1778 during endogenous and exogenous DSBs (DNA replication and whole
      cell or sub-nuclear microbeam irradiation, respectively). In non-stressed
      conditions, endogenous DSBs in S-phase cells led to accumulation of 53BP1 and
      gammaH2AX into discrete nuclear foci. Only the frank collapse of DNA replication
      forks following hydroxyurea treatment initiated 53BP1(Ser25) and 53BP1(Ser1778)
      phosphorylation. In response to exogenous DSBs, 53BP1(Ser25) and 53BP1(Ser1778)
      phosphoforms localized to sites of initial DSBs in a cell cycle-independent
      manner. 53BP1 phosphoforms also localized to late residual foci and associated
      with PML-NBs during IR-induced senescence. Using isogenic cell lines and small
      molecule inhibitors, we observed that DDR-induced 53BP1 phosphorylation was
      dependent on ATM and DNA-PKcs kinase activity but independent of MRE11 sensing or
      RNF168 chromatin remodeling. However, loss of RNF168 blocked recruitment of
      phosphorylated 53BP1 to sites of DNA damage. Our results uncouple 53BP1
      phosphorylation from DSB localization and support parallel pathways for 53BP1
      biology during the DDR. As relative 53BP1 expression may be a biomarker of DNA
      repair capacity in solid tumors, the tracking of 53BP1 phosphoforms in situ may
      give unique information regarding different cancer phenotypes or response to
      cancer treatment.

PMID- 22421154
TI  - Ribonuclease activity of p53 in cytoplasm in response to various stress signals.
AB  - The tumor suppressor p53 protein is expressed at low levels under normal
      conditions. The subcellular localization and functional activation of p53 are
      influenced by diverse stress signals. p53 in cytoplasm exerts intrinsic 3'->5'
      exonuclease activity with various RNA and DNA substrates. ssRNAs containing an
      adenosine and uridine-rich (ARE) element are permissive targets for p53-mediated
      degradation. The analysis of the exonuclease activity in cytoplasm with activated
      p53 induced by various drug treatments or following gamma-irradiation revealed
      that the expression of p53 exonuclease activity in response to stress signals is
      heterogeneous. Various genotoxic and non-genotoxic agents upregulate p53 yet have
      different effects on expression of exonuclease activity with ARE RNA but not with
      DNA substrate. Ribonuclease activity is enhanced in cytoplasmic extracts of
      HCT116 (p53+/+) cells exposed to gamma-irradiation or treated by the non
      genotoxic drug AS101 but decreased following treatment by genotoxic (e.g.,
      doxorubicin) or non-genotoxic (e.g., DFMO) agents, thus indicating that p53
      exonuclease activity is dependent on the specific stress and nature of the
      substrate. Apparently, the disparity in expression of p53 ribonuclease activity
      after each treatment is attributable to the different post-treatment response and
      to two posttranscriptional events: the interaction of RNA-binding HuR protein
      with ARE RNA protects the substrate from degradation by p53 and/or decrease in
      p53 ARE RNA binding capacity due to phosphorylation at Ser392 leads to reduction
      in p5 ribonuclease activity. Our results provide new insights into p53
      exonuclease function and into the mechanisms behind the regulation ARE-RNA
      degradation by p53 under different cellular conditions.

PMID- 22421155
TI  - Antiangiogenic agents: fueling cancer's hypoxic roots.

PMID- 22421157
TI  - MiRNA-34 intrinsically links p53 tumor suppressor and Wnt signaling.
AB  - Though tumor suppressor p53 and the canonical Wnt cascade have been extensively
      studied for the last 30 years, due to their important physiological roles, the
      two signaling pathways have been largely considered independent. Recently, the
      miR-34 family was found to directly link p53 and Wnt, revealing the tight
      connection between loss of tumor suppressor function and activation of oncogenic
      signaling. These observations demonstrate that miR-34, known to be directly
      downstream of p53, targets a set of highly conserved sites in the UTR of Wnt and
      EMT genes, specifically WNT1, WNT3, LRP6, AXIN2, beta-catenin, LEF1 and Snail,
      resulting in suppression of TCF/LEF transcriptional activity and the EMT program.
      The loss of p53 function increases Wnt activities and promotes the Snail
      dependent EMT program at multiple levels in a miR-34/UTR-specific manner. The
      TCF/LEF transcriptional signature was closely associated with functionality of
      p53 and miR-34 in clinical samples, suggesting the pervasive impact of miR-34
      loss on the oncogenic pathway in human cancer. Here, we review recent findings on
      ceRNA in light of novel data to elucidate the physiological relevance of the p53
      miR-34-Wnt network, which encompasses sets of genes and directions of signaling.
      As loss of wt-p53 or hyperactivation of Wnt is critical in maintaining cancer
      stem cell properties and in establishing the metastatic program, these
      observations indicate a mechanism of miR-mediated quasi-sufficiency which
      connects tumor suppressor and oncogenic signaling pathways, supporting a
      continuum model of human cancer.

PMID- 22421158
TI  - Code breaking: the RNAPII modification code in pluripotency.

PMID- 22421156
TI  - Dual role of hematopoietic progenitor kinase 1 (HPK1) as a positive regulator of
      1alpha,25-dihydroxyvitamin D-induced differentiation and cell cycle arrest of AML
      cells and as a mediator of vitamin D resistance.
AB  - Recent clinical trials aimed at improved treatment of AML by administration of
      vitamin D derivatives showed unremarkable results, suggesting development of
      vitamin D resistance in patients' AML blasts. Since mechanisms of vitamin D
      resistance are not clear, we studied 40AF cells, a subline of HL60 cells that can
      proliferate in the presence of 1alpha,25-dihydroxyvitamin D3 (1,25D). We found
      that mRNA and protein levels of HPK1, an upstream MAP4 kinase, are dramatically
      increased in 40AF cells, and HPK1 protein is further increased when the 1,25D
      resistance of 40AF cells is partially reversed by the addition of carnosic acid
      and p38MAPK inhibitor SB202190 (DCS cocktail). Knockdown of HPK1 reduces
      1,25D/DCS-induced differentiation of both 1,25D-sensitive HL60 and U937 cells and
      1,25D-resistant 40AF cells, but the effect of HPK1 knockdown on differentiation
      associated G 1 arrest is more apparent in the resistant than the sensitive cells.
      To explain why 40AF and the intrinsically vitamin D-resistant KG-1a cells can
      proliferate in the presence of vitamin D, we found that the cleaved HPK1 fragment
      (HPK1-C) level is high in 40AF and KG-1a cells, but when differentiation is
      induced by DCS, HPK1-C decreases while full-length (FL)-HPK1 increases.
      Accordingly, inhibition of proteolysis with the pan-caspase inhibitor Q-VD-OPh
      reduced HPK1 cleavage and enhanced DCS-induced differentiation of 40AF cells. The
      results indicate that FL-HPK1 is a positive regulator of vitamin D-induced
      differentiation in AML cells, but the cleaved HPK1 fragment inhibits
      differentiation. Thus, high HPK1 cleavage activity contributes to vitamin D
      resistance, and HPK1 has a dual role in AML cell differentiation.

PMID- 22421159
TI  - The p21-activated kinase Pak1 regulates induction and migration of the neural
      crest in Xenopus.
AB  - Pak1 is a member of the PAK family of serine/threonine kinases that are
      downstream effectors of Rac1 and Cdc42 small GTPases and are implicated in
      cytoskeleton reorganization. Early expression of Pak1 in Xenopus embryos is
      tissue restricted, suggesting a role in organogenesis and in cranial neural crest
      (CNC) cell migration. By observing CNC in vivo and after transplantation, we show
      that a dominant-negative (DN) Pak1 inhibits its migration. DN-Pak1 also
      specifically modified the expression of several NC markers. Twist expression was
      decreased and Snail1 expression posteriorized, but Snail2 (Slug), Sox9 and AP2
      were unaffected. DN-Pak1 inhibition of CNC migration could be rescued with Snail1
      but not with Twist, which, in fact, cooperated with DN-Pak1 in inhibiting
      migration. The data confirm that neither Snail1 nor Snail2 expression alone is
      sufficient for Xenopus CNC migration. Furthermore, they show that, in this
      tissue, Snail1 and Snail2 expression is not interdependent, nor are these factors
      subject to obligatory co-regulation, and that their expression depends on signal
      transduction. Our results also represent the first evidence that Pak1 links
      extracellular signals to the genetic cascade of transcription factors necessary
      for CNC specification.

PMID- 22421160
TI  - Monoclonal antibody-induced ErbB3 receptor internalization and degradation
      inhibits growth and migration of human melanoma cells.
AB  - Members of the ErbB receptor family are targets of a growing numbers of small
      molecules and monoclonal antibodies inhibitors currently under development for
      the treatment of cancer. Although historical efforts have been directed against
      ErbB1 (EGFR) and ErbB2 (HER2/neu), emerging evidences have pointed to ErbB3 as a
      key node in the activation of proliferation/survival pathways from the ErbB
      receptor family and have fueled enthusiasm toward the clinical development of
      anti-ErbB3 agents. In this study, we have evaluated the potential therapeutic
      efficacy of a set of three recently generated anti-human ErbB3 monoclonals, A2,
      A3 and A4, in human primary melanoma cells. We show that in melanoma cells
      expressing ErbB1, ErbB3 and ErbB4 but not ErbB2 receptor ligands activate the
      PI3K/AKT pathway, and this leads to increased cell proliferation and migration.
      While antibodies A3 and A4 are able to potently inhibit ligand-induced signaling,
      proliferation and migration, antibody A2 is unable to exert this effect. In
      attempt to understand the mechanism of action and the basis of this different
      behavior, we demonstrate, through a series of combined approaches, that antibody
      efficacy strongly correlates with antibody-induced receptor internalization,
      degradation and inhibition of receptor recycling to the cell surface. Finally,
      fine epitope mapping studies through a peptide array show that inhibiting vs. non
      inhibiting antibodies have a dramatically different mode of binding to the to the
      receptor extracellular domain. Our study confirms the key role of ErbB3 and
      points to exploitation of novel combination therapies for treatment of malignant
      melanoma.

PMID- 22421161
TI  - The peptidyl prolyl isomerase cyclophilin A localizes at the centrosome and the
      midbody and is required for cytokinesis.
AB  - Failed cytokinesis leads to tetraploidy, which is an important intermediate
      preceding aneuploidy and the onset of tumorigenesis. The centrosome is required
      for the completion of cytokinesis through the transport of important components
      to the midbody; however, the identity of molecular components and the mechanism
      involved remains poorly understood. In this study, we report that the peptidyl
      prolyl isomerase cyclophilin A (cypA) is a centrosome protein that undergoes cell
      cycle-dependent relocation to the midzone and midbody during cytokinesis in
      Jurkat cells implicating a role during division. Depletion of cypA does not
      disrupt mitotic spindle formation or progression through anaphase; however, it
      leads to cytokinesis defects through an inability to resolve intercellular
      bridges, culminating in delayed or failed cytokinesis. Defective cytokinesis is
      also evident by an increased prevalence of midbody-arrested cells. Expression of
      wild-type cypA reverses the cytokinesis defect in knockout cells, whereas an
      isomerase mutant does not, indicating that the isomerisation activity of cypA is
      required for cytokinesis. In contrast, wild-type cypA and the isomerase mutant
      localize to the centrosome and midbody, suggesting that localization to these
      structures is independent of isomerase activity. Depletion of cypA also generates
      tetraploid cells and supernumerary centrosomes. Finally, colony formation in soft
      agar is impaired in cypA-knockout cells, suggesting that cypA confers clonogenic
      advantage on tumor cells. Collectively, this data reveals a novel role for cypA
      isomerase activity in the completion of cytokinesis and the maintenance of genome
      stability.

PMID- 22421162
TI  - The many ways to open the gate to colon cancer.

PMID- 22421163
TI  - Sleep endoscopy as a diagnostic tool in pediatric obstructive sleep apnea.
AB  - OBJECTIVES: Ten to twenty percent of children have persistent obstructive sleep
      apnea (OSA) after adenotonsillectomy (T&A). We hypothesize that sleep endoscopy,
      a flexible fiberoptic examination of the pharynx under anesthesia, is an
      effective tool for identifying sites of persistent obstruction. METHODS: In this
      retrospective cohort study, we reviewed records of children who had symptoms
      consistent with OSA and a positive polysomnogram (PSG) who underwent sleep
      endoscopy followed by sleep endoscopy directed surgery. Data collection included
      age, BMI and co-morbidities. Apnea-hypopnea index (AHI) was compared to pre and
      post surgery for each child using a paired t-test. RESULTS: Of the 80 children
      who underwent sleep endoscopy followed by directed surgery, 65% were male, mean
      age was 6 years (SD 3.75 years), average BMI was 19 (SD 0.43 years) and 28% had
      co-morbidities. For the 51% of patients who had persistent OSA after T&A, the
      mean AHI after sleep endoscopy directed surgery was significantly lower then
      before surgery (7.9 vs. 15.7, p<.01). For the 49% of patients who had never
      undergone surgery for OSA, or who were surgically naive, and underwent sleep
      endoscopy directed surgery, the mean AHI was significantly lower then before
      surgery (8.0 vs. 13.8, p<.01). CONCLUSIONS: Sleep endoscopy is a consistently
      reliable tool for identifying the sites of obstruction in both surgically naive
      children and those with persistent OSA after T&A.

PMID- 22421164
TI  - The Hanle effect and electron spin polarization in InAs/GaAs quantum dots up to
      room temperature.
AB  - The Hanle effect in InAs/GaAs quantum dots (QDs) is studied under optical
      orientation as a function of temperature over the range of 150-300 K, with the
      aim of understanding the physical mechanism responsible for the observed sharp
      increase of electron spin polarization with increasing temperature. The deduced
      spin lifetime T(s) of positive trions in the QDs is found to be independent of
      temperature, and is also insensitive to excitation energy and density. It is
      argued that the measured T(s) is mainly determined by the longitudinal spin-flip
      time (T(1)) and the spin dephasing time (T(2)*) of the studied QD ensemble, of
      which both are temperature independent over the studied temperature range and the
      latter makes a larger contribution. The observed sharply rising QD spin
      polarization degree with increasing temperature, on the other hand, is shown to
      be induced by an increase in spin injection efficiency from the barrier/wetting
      layer and also by a moderate increase in spin detection efficiency of the QD.

PMID- 22421166
TI  - The gestures ASL signers use tell us when they are ready to learn math.
AB  - The manual gestures that hearing children produce when explaining their answers
      to math problems predict whether they will profit from instruction in those
      problems. We ask here whether gesture plays a similar role in deaf children,
      whose primary communication system is in the manual modality. Forty ASL-signing
      deaf children explained their solutions to math problems and were then given
      instruction in those problems. Children who produced many gestures conveying
      different information from their signs (gesture-sign mismatches) were more likely
      to succeed after instruction than children who produced few, suggesting that
      mismatch can occur within-modality, and paving the way for using gesture-based
      teaching strategies with deaf learners.

PMID- 22421167
TI  - Children expect generic knowledge to be widely shared.
AB  - The ability to acquire and store generic information (that is, information about
      entire categories) is at the core of human cognition. Remarkably, even young
      children place special value on generic information, often inferring that it
      holds important insights about the world. Here, we tested whether children's
      assumptions about the nature of generic information guide their expectations
      about how widely known this information is. Across four experiments, 4- to 7-year
      old children (N=192) were presented with novel facts in either generic (e.g.,
      "Hedgehogs eat hexapods") or non-generic (e.g., "This hedgehog eats hexapods")
      format and were asked whether other people (e.g., their moms, grown-ups in
      general) knew these facts. Overall, children were more likely to say that others
      knew the generic than the non-generic facts. In addition to highlighting the
      centrality of generic knowledge in early cognitive life, children's assumption
      that generic facts are widely known has implications for their social cognition
      and academic achievement, as well as for the process of language acquisition.

PMID- 22421165
TI  - The decrease of dopamine D2/D3 receptor densities in the putamen and nucleus
      caudatus goes parallel with maintained levels of CB1 cannabinoid receptors in
      Parkinson's disease: a preliminary autoradiographic study with the selective
      dopamine D2/D3 antagonist [3H]raclopride and the novel CB1 inverse agonist
      [125I]SD7015.
AB  - Cannabinoid type-1 receptors (CB1Rs) modulate synaptic neurotransmission by
      participating in retrograde signaling in the adult brain. Increasing evidence
      suggests that cannabinoids through CB1Rs play an important role in the regulation
      of motor activities in the striatum. In the present study, we used human brain
      samples to examine the relationship between CB1R and dopamine receptor density in
      case of Parkinson's disease (PD). Post mortem putamen, nucleus caudatus and
      medial frontal gyrus samples obtained from PD patients were used for CB1R and
      dopamine D2/D3 receptor autoradiography. [125I]SD7015, a novel selective CB1R
      inverse agonist, developed by a number of the present co-authors, and
      [3H]raclopride, a dopamine D2/D3 antagonist, were used as radioligands. Our
      results demonstrate unchanged CB1R density in the putamen and nucleus caudatus of
      deceased PD patients, treated with levodopa (L-DOPA). At the same time dopamine
      D2/D3 receptors displayed significantly decreased density levels in case of PD
      putamen (control: 47.97 +/- 10.00 fmol/g, PD: 3.73 +/- 0.07 fmol/g (mean +/-
      SEM), p<0.05) and nucleus caudatus (control: 30.26 +/- 2.48 fmol/g, PD: 12.84 +/-
      5.49 fmol/g, p<0.0005) samples. In contrast to the putamen and the nucleus
      caudatus, in the medial frontal gyrus neither receptor densities were affected.
      Our data suggest the presence of an unaltered CB1R population even in late stages
      of levodopa treated PD. This further supports the presence of an intact CB1R
      population which, in line with the conclusion of earlier publications, may be
      utilized as a pharmacological target in the treatment of PD. Furthermore we found
      discrepancy between a maintained CB1R population and a decreased dopamine D2/D3
      receptor population in PD striatum. The precise explanation of this conundrum
      requires further studies with simultaneous examination of the central cannabinoid
      and dopaminergic systems in PD using higher sample size.

PMID- 22421168
TI  - Feasibility, accuracy, and reproducibility of real-time full-volume 3D
      transthoracic echocardiography to measure LV volumes and systolic function: a
      fully automated endocardial contouring algorithm in sinus rhythm and atrial
      fibrillation.
AB  - OBJECTIVES: To assess the feasibility, accuracy, and reproducibility of real-time
      full-volume 3-dimensional transthoracic echocardiography (3D RT-VTTE) to measure
      left ventricular (LV) volumes and ejection fraction (EF) using a fully automated
      endocardial contouring algorithm and to identify and automatically correct the
      contours to obtain accurate LV volumes in sinus rhythm and atrial fibrillation
      (AF). BACKGROUND: 3D transthoracic echocardiography is not used routinely to
      quantify LV volumes and EF. A fully automated workflow using RT-VTTE may improve
      clinical adoption. METHODS: RT-VTTE was performed and 3D EF and volumes obtained
      using an automated trabecular endocardial contouring algorithm; an automated
      correction was applied to track the compacted myocardium. Cardiac magnetic
      resonance (CMR) and 2-dimensional biplane Simpson method were the reference
      standard. RESULTS: Ninety-one patients (67 in normal sinus rhythm [NSR], 24 in
      AF) were included. Among all NSR patients, there was excellent correlation
      between RT-VTTE and CMR for end-diastolic volume (EDV), end-systolic volume
      (ESV), and EF (r = 0.90, 0.96, and 0.98, respectively; p < 0.001). In patients
      with EF >=50% (n = 36), EDV and ESV were underestimated by 10.7 +/- 17.5 ml (p =
      0.001) and by 4.1 +/- 6.1 ml (p < 0.001), respectively. In those with EF <50% (n
      = 31), EDV and ESV were underestimated by 25.7 +/- 32.7 ml (p < 0.001) and by
      16.2 +/- 24.0 ml (p = 0.001). Automated contour correction to track the compacted
      myocardium eliminated mean volume differences between RT-VTTE and CMR. In
      patients with AF, LV volumes and EF were accurate by RT-VTTE (r = 0.94, 0.94, and
      0.91 for EDV, ESV, and EF, respectively; p < 0.001). Automated 3D LV volumes and
      EF were highly reproducible. CONCLUSIONS: Rapid, accurate, and reproducible EF
      can be obtained by RT-VTTE in NSR and AF patients by using an automated
      trabecular edge contouring algorithm. Furthermore, automated contour correction
      to detect the compacted myocardium yields accurate and reproducible 3D LV
      volumes.

PMID- 22421169
TI  - Asymptomatic individuals with a positive family history for premature coronary
      artery disease and elevated coronary calcium scores benefit from statin
      treatment: a post hoc analysis from the St. Francis Heart Study.
AB  - OBJECTIVES: The goal of this study was to evaluate whether individuals with a
      positive family history for premature coronary artery disease (CAD) and coronary
      calcium scoring (CCS) above the 80th percentile might benefit from preventive
      treatment. BACKGROUND: First-degree relatives of patients with premature CAD have
      an increased risk for cardiovascular disease (CVD), whereas events are poorly
      predicted in these individuals. Surrogate markers, such as CCS, might refine risk
      scoring. Nevertheless, the outcome of the St. Francis Heart trial, which
      investigated the effect of atorvastatin 20 mg/day in asymptomatic individuals
      with CCS above the 80th percentile, did not reach statistical significance.
      METHODS: We performed a post hoc analysis on the database of the St. Francis
      trial to assess efficacy of treatment with atorvastatin 20 mg/day in those with
      CCS above the 80th percentile and presence (n = 543) or absence (n = 462) of a
      positive family history for premature CAD. All participants received aspirin 81
      mg/day. Primary outcome included coronary death, myocardial infarction, coronary
      revascularization, stroke, and arterial surgery. RESULTS: A total of 1,005
      individuals, with a mean age of 59.0 +/- 5.9 years and a median absolute CCS of
      370 Agatston units (interquartile range: 183 to 662) participated in the trial.
      After a follow-up of 4.3 (interquartile range: 3.5 to 4.5) years, 7.2% of the
      treated individuals with a positive family history had a cardiovascular event
      versus 12.5% of the placebo group (hazard ratio [HR]: 0.55; 95% confidence
      intervals [CI]: 0.31 to 0.97; p = 0.040). This is comparable with a number needed
      to treat of 18.9. In individuals without a family history, events were minimally
      reduced: 6.6% in the treated versus 6.8% in the placebo group (HR: 1.04; 95% CI:
      0.51 to 2.13; p = 0.912). CONCLUSIONS: The combination of a positive family
      history and CCS above the 80th percentile identifies a subgroup within the
      primary prevention population that receives greater benefit from statin treatment
      than the population at large. These results have important implications for
      future guidelines concerning individuals with a positive family history for
      premature CAD.

PMID- 22421170
TI  - Statin therapy for subclinical atherosclerosis in primary prevention: time to
      prove it?

PMID- 22421171
TI  - Calcium scoring in patients with a history of Kawasaki disease.
AB  - OBJECTIVES: The goal of this study was to assess coronary artery calcification in
      patients >=10 years or age with a history of Kawasaki disease (KD). BACKGROUND:
      Patients with a history of KD and coronary artery aneurysms are at risk for late
      morbidity from coronary artery events. It is unknown whether patients with KD
      with acutely normal or transiently dilated coronary arteries also have increased
      risk of late coronary artery complications. Coronary calcium scoring using
      noncontrast computed tomography is a well-established tool for risk-stratifying
      patients with atherosclerotic coronary artery disease, but there are limited data
      on its role in evaluating patients with a history of KD. METHODS: We performed
      coronary artery calcium (CAC) volume scoring using a low radiation dose computed
      tomography protocol on 70 patients (median age 20.0 years) with a remote history
      of KD (median interval from acute KD to imaging 14.8 years). Forty-four (63%)
      patients had no history of coronary dilation, 12 (17%) had a history of transient
      dilation, and 14 (20%) had coronary aneurysms. RESULTS: All of the patients with
      normal coronary artery internal diameter during the acute phase of KD and 11 of
      12 patients with transient dilation had CAC scores of zero. Coronary
      calcification was observed in 10 of the 14 patients with coronary aneurysms, with
      the degree of calcification ranging from mild to severe and occurring years after
      the patients' acute KD. CONCLUSIONS: Coronary calcification was not observed in
      patients with a history of KD and normal coronary arteries during the acute
      phase. Therefore, CAC scanning may be a useful tool to screen patients with a
      remote history of KD or suspected KD and unknown coronary artery status. Coronary
      calcification, which may be severe, occurs late in patients with coronary
      aneurysms. The pathophysiology and clinical implications of coronary
      calcification in patients with aneurysms are currently unknown and warrant
      further study.

PMID- 22421173
TI  - Ventricular torsion: an aid to ejection?

PMID- 22421172
TI  - Relation of torsion and myocardial strains to LV ejection fraction in
      hypertension.
AB  - OBJECTIVES: The goal of this study was to define the mechanism of preserved
      ejection fraction (EF) despite depressed myocardial strains in hypertension
      (HTN). BACKGROUND: Concentric left ventricular (LV) remodeling in HTN may have
      normal or supranormal EF despite depressed myocardial strains. The reason for
      such discordance is not clear. The aim of this study was to comprehensively
      evaluate the LV mechanics in a well-defined HTN population to define underlying
      reasons for such a paradox. METHODS: Sixty-seven patients with resistant HTN and
      45 healthy control subjects were studied by cardiac magnetic resonance imaging
      and tissue tagging with 3-dimensional analysis. Amplitude and directional vector
      of longitudinal (Ell), circumferential (Ecc), and principal strain for maximal
      shortening (E3) were computed at basal, mid, and distal LV levels, respectively.
      LV torsion, defined as the rotation angle of apex relative to base, and LV twist,
      which accounts for the effects of differential LV remodeling on torsion for
      comparison among the 2 groups, were also calculated. RESULTS: LV mass index and
      LV mass/LV end-diastolic volume ratio were significantly higher in the HTN group
      compared with controls, consistent with concentric LV remodeling. Ell and Ecc
      were significantly decreased in amplitude with altered directional vector in HTN
      compared with controls. However, the amplitude of E3 was similar in the 2 groups.
      Torsion and twist were significantly higher in HTN, which was mainly due to
      increase in apical rotation. The HTN group demonstrated significantly increased
      LV wall thickening compared with controls that resulted in greater LVEF in the
      HTN group compared with controls (70% vs. 65%, p < 0.001, respectively).
      CONCLUSIONS: In compensated LV remodeling secondary to HTN, there is increased LV
      wall thickening with preserved E3 and increased torsion compared with normal
      controls. This, therefore, contributes to supranormal LVEF in HTN despite
      depressed longitudinal and circumferential strains.

PMID- 22421174
TI  - 4-[18F]-tetraphenylphosphonium as a PET tracer for myocardial mitochondrial
      membrane potential.
AB  - OBJECTIVES: This study tested the hypothesis that 4
      [(18)F]fluorophenyltriphenylphosphonium ((18)F-TPP) is useful for in vivo
      positron emission tomography (PET) measurement of mitochondrial membrane
      potential (DeltaPsim). Its utility as a blood flow tracer also was evaluated.
      BACKGROUND: Tetraphenylphosphonium is useful for in vitro measurement of
      DeltaPsim. In vivo measurement of DeltaPsim has potential value in the assessment
      of heart failure pathophysiology and therapy as well as assessment of myocardial
      viability and so may be a very useful clinical tool. METHODS: Anesthetized swine
      (N = 6) with a balloon catheter in the left anterior descending coronary artery
      were studied. Microsphere measurements of myocardial blood flow (MBF) were made
      after balloon inflation (baseline) and ~10 min after intravenous administration
      of adenosine and phenylephrine after which ~10 mCi (18)F-TPP was injected
      intravenously and dynamic PET data acquisition obtained for 30 min. After the
      swine were killed, the hearts were sectioned for microsphere measurement of MBF
      and (18)F-TPP measured by well counter in these same samples. PET images provided
      whole blood and myocardial (18)F-TPP concentration for determination of DeltaPsim
      by the Nernst equation, corrected for nonspecific (18)F-TPP binding. Microsphere
      MBF, absolute (ml/min/g) and relative, was compared with PET data (standard
      uptake value and K1). RESULTS: Nonspecific binding of (18)F-TPP overestimated
      DeltaPsim measured by -37 +/- 4 mV (mean +/- SD). Normal zone DeltaPsim of ex
      vivo samples (-91 +/- 11 mV; N = 52; sample weight, 1.07 +/- 0.18 g) correlated
      strongly (R(2)= 0.93) with normal zone by PET (-81 +/- 13 mV). Both ex vivo and
      PET normal zone DeltaPsim, although somewhat lower, compared well with that
      reported for tritium labeled triphenylphosphonium in normal working Langendorff
      rat heart (-100 mV). Although the relative MBF by (18)F-TPP correlated strongly
      with relative microsphere MBF (R(2)= 0.83), there was no correlation between
      absolute MBF by (18)F-TPP and microsphere MBF. CONCLUSIONS: (18)F-TPP is a
      promising tracer for noninvasive PET measurement of DeltaPsim in living subjects.
      It is useful as well for assessment of relative but not absolute MBF.

PMID- 22421175
TI  - Myocardial imaging for mitochondrial membrane potential.

PMID- 22421176
TI  - Distance of lipid core-rich plaques from the ostium by NIRS in nonculprit
      coronary arteries.

PMID- 22421177
TI  - Temporal enhancement of 3D echocardiography by frame reordering.
AB  - We describe a method to increase the frame rate for 3-dimensional ultrasound
      sequences of periodically moving cardiac structures by reordering the acquired
      volume series. The frame rate is especially important in studying intracardiac
      structures such as valve leaflet motion in which valve closing times are on the
      order of milliseconds. Current commercially available systems for volumetric
      ultrasound imaging are limited to approximately 10 to 20 volumes per second.
      Although this frame rate is sufficient for real-time observation of basic cardiac
      morphology, understanding cardiac dynamics requires faster frame rates. The
      presented work achieves higher frame rates by sampling over several beats and
      using a simultaneous electrocardiography signal to accurately place the frame
      within the cardiac cycle. The proposed method relies on periodicity of the heart
      motion and that within the temporal regions of highest velocity, the structural
      motions of interest have the lowest beat-to-beat variability.

PMID- 22421178
TI  - Emerging trends in CV flow visualization.
AB  - Blood flow patterns are closely linked to the morphology and function of the
      cardiovascular system. These patterns reflect the exceptional adaptability of the
      cardiovascular system to maintain normal blood circulation under a wide range of
      workloads. Accurate retrieval and display of flow-related information remains a
      challenge because of the processes involved in mapping the flow velocity fields
      within specific chambers of the heart. We review the potentials and pitfalls of
      current approaches for blood flow visualization, with an emphasis on acquisition,
      display, and analysis of multidirectional flow. This document is divided into 3
      sections. First, we provide a descriptive outline of the relevant concepts in
      cardiac fluid mechanics, including the emergence of rotation in flow and the
      variables that delineate vortical structures. Second, we elaborate on the main
      methods developed to image and visualize multidirectional cardiovascular flow,
      which are mainly based on cardiac magnetic resonance, ultrasound Doppler, and
      contrast particle imaging velocimetry, with recommendations for developing
      dedicated imaging protocols. Finally, we discuss the potential clinical
      applications and technical challenges with suggestions for further
      investigations.

PMID- 22421179
TI  - The year in molecular imaging.

PMID- 22421180
TI  - Detection of patent foramen ovale by 3D echocardiography.

PMID- 22421181
TI  - MR imaging in patients with pacemakers and other devices: engineering the future.

PMID- 22421182
TI  - Vulnerable plaques: from PROSPECT to prospects....

PMID- 22421183
TI  - Simian virus 40 efficiently infects human T lymphocytes and extends their
      lifespan.
AB  - The relevance of viral infections to the onset and progression of human
      hematologic malignancies and other blood diseases is still a matter of active
      investigation. Purified human T lymphocytes isolated from the peripheral blood
      mononuclear cells of healthy blood donors were experimentally infected with
      simian virus 40 (SV40), a small DNA tumor virus. SV40-positive T lymphocytes
      extended their lifespan up to day 80 postinfection (PI). Expression of viral
      antigens, such as the large T antigen and the viral capsid protein VP1 from the
      early and late regions, respectively, was detected up to day 40 PI. SV40 viral
      progeny were continuously produced from day 10 to 40 PI. SV40 DNA sequences were
      detected in infected T cells for up to 80 days. Our data indicate that human T
      lymphocytes can be efficiently infected with SV40. Although T cells infected by
      SV40 were not immortalized, 30% of these lymphocytes appeared to be
      morphologically transformed with an enlarged T-cell shape. Our investigation
      provides a simple model for studying the interactions of human T lymphocytes with
      this small DNA tumor virus and it might represent an experimental tool for
      investigating new biomarkers and targets for innovative therapeutic approaches.

PMID- 22421184
TI  - Connexin multi-site phosphorylation: mass spectrometry-based proteomics fills the
      gap.
AB  - Connexins require an integrated network for protein synthesis, assembly, gating,
      internalization, degradation and feedback control that are necessary to regulate
      the biosynthesis, and turnover of gap junction channels. At the most fundamental
      level, the introduction of sequence-altering, modifications introduces changes in
      protein conformation, activity, charge, stability and localization. Understanding
      the sites, patterns and magnitude of protein post-translational modification,
      including phosphorylation, is absolutely critical. Historically, the examination
      of connexin phosphorylation has been placed within the context that one or small
      number of sites of modification strictly corresponds to one molecular function.
      However, the release of high-profile proteomic datasets appears to challenge this
      dogma by demonstrating connexins undergo multiple levels of multi-site
      phosphorylation. With the growing prominence of mass spectrometry in biology and
      medicine, we are now getting a glimpse of the richness of connexin phosphate
      signals. Having implications to health and disease, this review provides an
      overview of technologies in the context of targeted and discovery proteomics, and
      further discusses how these techniques are being applied to "fill the gaps" in
      understanding of connexin post-translational control. This article is part of a
      Special Issue entitled: The Communicating junctions, roles and dysfunctions.

PMID- 22421185
TI  - Rufinamide as an adjuvant treatment in children with Lennox-Gastaut syndrome.
AB  - PURPOSE: To evaluate the efficacy of rufinamide as an add-on treatment in
      children and adolescents with Lennox-Gastaut syndrome (LGS). METHODS: The study
      was an open-label, observational clinical trial of rufinamide as an add-on
      treatment in intractable LGS patients. This intent-to-treat trial included 4
      weeks of scheduled titrated doses and a 12-week maintenance phase with a target
      dose of 20-40 mg/kg rufinamide, adjusted according to its effectiveness and
      tolerability after a baseline period of 4 weeks. The primary outcome was measured
      by the seizure-reduction rate according to individual seizure type over the 12
      week maintenance period. RESULTS: One hundred and twenty-eight patients with LGS
      who were determined to be unresponsive to one or more antiepileptic drugs or
      dietary therapy were enrolled. Of the 128 patients enrolled, 112 (87.5%)
      completed the study. After add-on rufinamide treatment, 46 patients (35.9%)
      achieved a more than 50% reduction in seizure frequency and 10 (7.8%) patients
      became seizure-free. When we identified those who responded with an at least 50%
      reduction in seizure frequency, 39.4% of the responders reported reductions in
      convulsive seizures, 36.4% in drop attacks, 33.3% in myoclonic seizures, and
      20.0% in epileptic spasms. Overall, 32.8% of patients reported adverse effects,
      which were mostly mild and transient in nature. The most common adverse effects
      were fatigue (15 patients, 11.7%) and poor appetite (9 patients, 7.0%). Twenty
      one (16.4%) patients experienced an increased seizure frequency. CONCLUSIONS:
      Rufinamide appears to be a safe and effective adjuvant treatment for many cases
      of intractable LGS.

PMID- 22421186
TI  - Within-day reliability of shoulder range of motion measurement with a smartphone.
AB  - Measuring range of motion (ROM) is the first step of a physical examination and
      functional evaluation of the shoulder joint. Digital inclinometers are available
      on the market; however, they are expensive, and hence will not come into wide
      use. In this study, we present a new method for the shoulder ROM measurement
      using the inclinometer application on a smartphone. We hypothesized that the
      method would demonstrate acceptable reliability and reproducibility. Three
      observers performed goniometric and smartphone inclinometric measurements of
      various shoulder movements, including both active and passive ROM for forward
      flexion, abduction, external rotation while the arms are at the sides, external
      rotation at 90 degrees  abduction, and internal rotation at 90 degrees 
      abduction. Measurements were performed in the affected shoulders of 41 patients.
      All measurements were taken twice to assess the intra-observer reliability. Inter
      and intra-observer reliabilities were evaluated using the intraclass correlation
      coefficient (ICC). Reliability between two measurements was also assessed in
      terms of the ICC. Both the goniometric and inclinometric measurements showed
      satisfactory inter-observer reliability except for internal rotation at 90
      degrees  abduction for which the ICC value was <0.7 (range, 0.63-0.68). Intra
      observer reliability was excellent with an ICC value>0.9, except for some
      movements. Within-day inclinometric measurements with a smartphone showed
      acceptable reliability compared to the classical goniometric measurements of
      movements and the correlation between the two measurements was fairly high.
      Considering convenience and cost-effectiveness, this new method could be widely
      used for measuring the shoulder ROM, although the between-day reliability needs
      to be established first.

PMID- 22421187
TI  - Spinal manual therapy produces rapid onset analgesia in a rodent model.
AB  - A rapid hypoalgesic effect following spinal manual therapy (SMT) has been
      demonstrated in humans. Although the characteristics of the pain relief are well
      described, the mechanisms have remained speculative. The purpose of this suite of
      studies was to investigate the effects of SMT on pain measures using animal
      models. This study employed a randomized, controlled design. Study 1: Rats
      without inflammation were allocated to either a treatment group (n = 6) that
      received three applications of joint mobilization centrally over L5 or a sham
      treated group (n = 6) who received non-specific handling. Pressure pain threshold
      (PPT) and thermal pain threshold (TPT) were measured before and immediately after
      each intervention. Results demonstrated significantly increased mechanical
      nociceptive thresholds in the SMT group (p = 0.01) compared to that of the sham
      treated group but no difference for thermal nociceptive thresholds. Study 2: The
      time course effect of an inflammatory and mechanical response following i.pl
      injection of inflammatory mediators was investigated to determine the appropriate
      time period for a treatment intervention. Study 3: The effects of SMT on
      mechanical nociception were investigated following interplanar injection of
      inflammatory mediators into the right hind paw of rats as a pain model (n = 6 for
      both SMT and sham-treated groups). Injection of endogenous metabolites produced
      significant swelling and flaring as well as increased PPT values following SMT (p
      < 0.02) compared with controls. These results demonstrate a rapid analgesic
      response following application of SMT, which has similar characteristics as that
      seen in both symptomatic and asymptomatic human populations.

PMID- 22421188
TI  - The efficacy of targeted interventions for modifiable psychosocial risk factors
      of persistent nonspecific low back pain - a systematic review.
AB  - BACKGROUND: There is considerable interest in whether best practice management of
      nonspecific low back pain (NSLBP) should include the targeting of treatment to
      subgroups of people with identifiable clinical characteristics. However, there
      are no published systematic reviews of the efficacy of targeted psychosocial
      interventions. AIM: This review aimed to determine if the efficacy of
      interventions for psychosocial risk factors of persistent NSLBP is improved when
      targeted to people with particular psychosocial characteristics. METHOD:
      Bibliographic databases were searched. Inclusion criteria were randomised
      controlled trials of targeted psychosocial interventions that used trial designs
      capable of providing robust information on the efficacy of targeted treatment
      (treatment effect modification) for the outcomes of pain, activity limitation and
      psychosocial factors (fear avoidance, catastrophisation, anxiety and depression).
      RESULTS AND CONCLUSION: Four studies met the inclusion criteria and collectively
      investigated nine hypotheses about targeted treatment on 28 subgroup/treatment
      outcomes. There were only two statistically significant results. Graded activity
      plus Treatment Based Classification targeted to people with high movement-related
      fear was more effective than Treatment Based Classification at reducing movement
      related fear at 4 weeks. Active rehabilitation (physical exercise classes with
      cognitive-behavioural principles) was more effective than usual GP care at
      reducing activity limitation at 12 months, when targeted to people with higher
      movement-related pain. Few studies have investigated targeted psychosocial
      interventions in NSLBP, using trial designs suitable for measuring treatment
      effect modification, and they do not provide consistent evidence supporting such
      targeting. There is a need for appropriately designed and adequately powered
      trials to investigate targeted psychosocial interventions.

PMID- 22421189
TI  - Validity of a Smartphone-based instrumented Timed Up and Go.
AB  - The Timed Up and Go (TUG) is one of the most widely used clinical tests to assess
      balance and mobility. An instrumented Timed Up and Go (iTUG) makes use of a
      specialized measurement system (e.g. an accelerometer) to identify and evaluate
      specific mobility skills. Nowadays a Smartphone (SP) comes with a large set of
      embedded sensors, including an accelerometer. An SP is a user-friendly device
      able to perform ubiquitous sensing with a variety of connectivity options. In
      this study we evaluate the validity of an SP for instrumenting the TUG. We
      examined 49 subjects (59 +/- 16 years old), without defining any inclusion
      criteria, using both an SP and a McRoberts Dynaport Hybrid, a device specifically
      designed for movement analysis. The statistical agreement between the two
      measurement systems is good for some of the parameters described in literature,
      which are of clear clinical value. Inter-rater reliability is often excellent and
      intra-rater reliability has been assessed in a subgroup of 25 subjects finding
      the same results for the two devices. In conclusion we found evidence that the SP
      is capable of becoming a pervasive and low-cost tool for the quantitative
      analysis of balance and mobility.

PMID- 22421190
TI  - Analysis of a kinetic multi-segment foot model. Part I: Model repeatability and
      kinematic validity.
AB  - Kinematic multi-segment foot models are still evolving, but have seen increased
      use in clinical and research settings. The addition of kinetics may increase
      knowledge of foot and ankle function as well as influence multi-segment foot
      model evolution; however, previous kinetic models are too complex for clinical
      use. In this study we present a three-segment kinetic foot model and thorough
      evaluation of model performance during normal gait. In this first of two
      companion papers, model reference frames and joint centers are analyzed for
      repeatability, joint translations are measured, segment rigidity characterized,
      and sample joint angles presented. Within-tester and between-tester repeatability
      were first assessed using 10 healthy pediatric participants, while kinematic
      parameters were subsequently measured on 17 additional healthy pediatric
      participants. Repeatability errors were generally low for all sagittal plane
      measures as well as transverse plane Hindfoot and Forefoot segments (median<3
      degrees ), while the least repeatable orientations were the Hindfoot coronal
      plane and Hallux transverse plane. Joint translations were generally less than
      2mm in any one direction, while segment rigidity analysis suggested rigid body
      behavior for the Shank and Hindfoot, with the Forefoot violating the rigid body
      assumptions in terminal stance/pre-swing. Joint excursions were consistent with
      previously published studies.

PMID- 22421191
TI  - Phase I trial of intraperitoneal pemetrexed, cisplatin, and paclitaxel in
      optimally debulked ovarian cancer.
AB  - PURPOSE: This phase I trial evaluated intraperitoneal (i.p.) pemetrexed,
      cisplatin, and paclitaxel in optimally debulked ovarian cancer. EXPERIMENTAL
      DESIGN: Dose escalation of day 1 i.p. pemetrexed accrued three patients to each
      of five dose levels (60-1,000 mg/m(2)), along with day 2 i.p. cisplatin (75
      mg/m(2)) and day 8 i.p. paclitaxel (60 mg/m(2)). The goals were to determine
      maximum tolerated dose (MTD), 18-month progression-free survival (PFS), and
      pharmacokinetics of i.p. pemetrexed. RESULTS: Cycles, given every 21 days, had an
      80% 6-cycle completion rate. There was minimal grade III toxicity in the first 4
      dose levels and remarkably an almost complete absence of peripheral neuropathy
      and alopecia. At the highest dose level, two of three patients experienced >=
      grade III and dose-limiting toxicity (DLT; hematologic, infection,
      gastrointestinal). There was a pharmacokinetic advantage for i.p. pemetrexed with
      an intraperitoneal:plasma area under the concentration-time curve ratio of 13
      fold. Neither analysis of pharmacokinetic nor homocysteine levels explains the
      unexpected severity of toxicity in those two patients. On the basis of plasma
      C(24h) levels, the 42 cycles at >= 500 mg/m(2) i.p. pemetrexed without DLT, the
      MTD appears to be 500 mg/m(2). Median PFS is 30.1 months; 18-month PFS is 78.6%
      (median follow-up 22.4 months). CONCLUSIONS: This i.p.-only regimen in front-line
      ovarian cancer is feasible with PFS in line with recent literature. We suggest
      phase II trials of this regimen in this population with i.p. pemetrexed at 500
      mg/m(2). The favorable toxicity profile at doses <1,000 mg/m(2), which needs to
      be confirmed, appears to compare well with standard combination i.v./i.p.
      platinum/taxane chemotherapy in this disease.

PMID- 22421192
TI  - A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of
      oncogenic, angiogenic, and stromal kinases, in patients with advanced solid
      tumors.
AB  - PURPOSE: Regorafenib is a novel oral multikinase inhibitor of angiogenic (VEGFR1
      3, TIE2), stromal (PDGFR-beta, FGFR), and oncogenic kinases (KIT, RET, and RAF).
      This first-in-man, phase I dose-escalation study assessed the safety,
      pharmacokinetic, pharmacodynamic, and efficacy profiles of regorafenib in
      patients with advanced solid tumors. PATIENTS AND METHODS: Patients aged 18 years
      or older with advanced solid tumors refractory to standard treatment were
      recruited. Regorafenib was administered orally for 21 days on/seven days off in
      repeating cycles, until discontinuation due to toxicity or tumor progression.
      Adverse events (AE) were assessed using National Cancer Institute Common
      Terminology Criteria for Adverse Events v3.0. Pharmacokinetic profiles were
      measured after a single dose and on day 21. Pharmacodynamic and efficacy
      evaluations included tumor perfusion assessment using dynamic contrast-enhanced
      MRI, plasma cytokines, and tumor response using RECIST (v1.0). RESULTS: Fifty
      three patients were enrolled into eight cohorts at dose levels from 10 to 220 mg
      daily. The recommended dose for future studies was determined to be 160 mg daily,
      with a treatment schedule of 21 days on/seven days off in repeating 28-day
      cycles. The most common drug-related grade 3 or 4 AEs were dermatologic AEs (hand
      foot skin reaction, rash), hypertension, and diarrhea. Pharmacokinetic analysis
      revealed a similar exposure at steady state for the parent compound and two
      pharmacologically active metabolites. Tumor perfusion and plasma cytokine
      analysis showed biologic activity of regorafenib. Three of 47 evaluable patients
      achieved a partial response (renal cell carcinoma, colorectal carcinoma, and
      osteosarcoma). CONCLUSION: Regorafenib showed an acceptable safety profile and
      preliminary evidence of antitumor activity in patients with solid tumors.

PMID- 22421193
TI  - Requirements to assess feasibility of phase 0 trials during major abdominal
      surgery: variability of PARP activity.
AB  - PURPOSE: The aim of this study was to evaluate the feasibility of phase 0 trials
      in the setting of a routine surgical procedure. Logistic considerations, tissue
      sampling and tissue handling, and variability of a biomarker during surgery, in
      here PARP, were evaluated. EXPERIMENTAL DESIGN: Patients with highly suspicious
      or proven diagnosis of advanced ovarian cancer, planned for debulking surgery
      were asked to allow sequential tumor biopsies during surgery. Biopsies were
      frozen immediately and PARP activity was measured subsequently. RESULTS: Baseline
      biopsies were obtained from eight patients after a median time of 88 minutes
      (minimum of 50 to maximum of 123 minutes). Second and third biopsies were
      obtained after a median of 60 (32-96) and 101 (79-130) minutes, respectively.
      Mean tumor load was 44% (5%-100%), with a cellular viability of 98% (85%-100%).
      Median baseline PARP activity was 1035 pg/mL (range, 429-2663 pg/mL). The
      observed interpatient variability at baseline was large: SD was 0.59 after
      natural logarithm transformation. CONCLUSIONS: Conducting phase 0 trials during
      surgery seems to be feasible in terms of logistic considerations. In preparation
      of a phase 0 trial during surgery, a feasibility study like this should be
      conducted to rule out major interactions of the surgical intervention with
      respect to the targeted biomarker.

PMID- 22421194
TI  - Detection of tumor PIK3CA status in metastatic breast cancer using peripheral
      blood.
AB  - PURPOSE: We sought to evaluate the feasibility of detecting PIK3CA mutations in
      circulating tumor DNA (ctDNA) from plasma of patients with metastatic breast
      cancer using a novel technique called BEAMing. EXPERIMENTAL DESIGN: In a
      retrospective analysis, 49 tumor and temporally matched plasma samples from
      patients with breast cancer were screened for PIK3CA mutations by BEAMing. We
      then prospectively screened the ctDNA of 60 patients with metastatic breast
      cancer for PIK3CA mutations by BEAMing and compared the findings with results
      obtained by screening corresponding archival tumor tissue DNA using both
      sequencing and BEAMing. RESULTS: The overall frequency of PIK3CA mutations by
      BEAMing was similar in both patient cohorts (29% and 28.3%, respectively). In the
      retrospective cohort, the concordance of PIK3CA mutation status by BEAMing
      between formalin-fixed, paraffin-embedded (FFPE) samples and ctDNA from
      temporally matched plasma was 100% (34 of 34). In the prospective cohort, the
      concordance rate among 51 evaluable cases was 72.5% between BEAMing of ctDNA and
      sequencing of archival tumor tissue DNA. When the same archival tissue DNA was
      screened by both sequencing and BEAMing for PIK3CA mutations (n = 41 tissue
      samples), there was 100% concordance in the obtained results. CONCLUSIONS:
      Analysis of plasma-derived ctDNA for the detection of PIK3CA mutations in
      patients with metastatic breast cancer is feasible. Our results suggest that
      PIK3CA mutational status can change upon disease recurrence, emphasizing the
      importance of reassessing PIK3CA status on contemporary (not archival)
      biospecimens. These results have implications for the development of predictive
      biomarkers of response to targeted therapies.

PMID- 22421195
TI  - Phase I study of vincristine, irinotecan, and 131I-metaiodobenzylguanidine for
      patients with relapsed or refractory neuroblastoma: a new approaches to
      neuroblastoma therapy trial.
AB  - PURPOSE: (131)I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical
      with activity in patients with relapsed or refractory neuroblastoma. Irinotecan
      is a known radiosensitizer with activity in neuroblastoma. This phase I study
      aimed to determine the recommended phase 2 dose of MIBG together with fixed doses
      of vincristine and irinotecan. EXPERIMENTAL DESIGN: Patients 1 to 30 years old
      with relapsed or refractory neuroblastoma and MIBG-avid tumors were eligible. All
      patients had autologous hematopoietic stem cells (PBSC) available and met
      standard phase I organ function requirements. Irinotecan (20 mg/m(2)/dose IV) was
      given on days 0 to 4 and 7 to 11, with vincristine (1.5 mg/m(2) IV) on days 0 and
      7. MIBG was given on day 1 following a 3 + 3 phase I dose escalation design
      starting at 8 mCi/kg MIBG. PBSCs were administered at dose level 8 mCi/kg for
      prolonged myelosuppression and for all patients at 12 mCi/kg or more. RESULTS:
      Twenty-four patients evaluable for dose escalation (median age, 6.7 years; range,
      1.9-26.8 years) received 1 (n = 17), 2 (n = 5), or 3 (n = 2) cycles of therapy.
      Myelosuppression and diarrhea were the most common toxicities. Two of 6 patients
      at the 18 mCi/kg dose level had dose-limiting toxicity (DLT), including one with
      protocol-defined DLT with prolonged mild aspartate aminotransferase elevation.
      Eighteen mCi/kg was the recommended phase 2 dose. Six additional patients were
      treated at 18 mCi/kg, with one additional DLT. Responses (2 complete and 4
      partial responses) occurred in 6 of 24 (25%) evaluable patients. CONCLUSIONS:
      MIBG is tolerable and active at 18 mCi/kg with standard doses of vincristine and
      irinotecan.

PMID- 22421196
TI  - Challenges of standardized continuous quality improvement programs in community
      pharmacies: the case of SafetyNET-Rx.
AB  - BACKGROUND: Research on continuous quality improvement (CQI) in community
      pharmacies lags in comparison to service, manufacturing, and various health care
      sectors. As a result, very little is known about the challenges community
      pharmacies face when implementing CQI programs in general, let alone the
      challenges of implementing a standardized and technologically sophisticated one.
      OBJECTIVE: This research identifies the initial challenges of implementing a
      standardized CQI program in community pharmacies and how such challenges were
      addressed by pharmacy staff. METHODS: Through qualitative interviews, a multisite
      study of the SafetyNET-Rx CQI program involving community pharmacies in Nova
      Scotia, Canada, was performed to identify such challenges. Interviews were
      conducted with the CQI facilitator (ie, staff pharmacist or technician) in 55
      community pharmacies that adopted the SafetyNET-Rx program. Of these 55
      pharmacies, 25 were part of large national corporate chains, 22 were part of
      banner chains, and 8 were independent pharmacies. A total of 10 different
      corporate chains and banners were represented among the 55 pharmacies. Thematic
      content analysis using well-established coding procedures was used to explore the
      interview data and elicit the key challenges faced. RESULTS: Six major challenges
      were identified, specifically finding time to report, having all pharmacy staff
      involved in quality-related event (QRE) reporting, reporting apprehensiveness,
      changing staff relationships, meeting to discuss QREs, and accepting the online
      technology. Challenges were addressed in a number of ways including developing a
      manual-online hybrid reporting system, managers paying staff to meet after hours,
      and pharmacy managers showing visible commitment to QRE reporting and learning.
      CONCLUSIONS: This research identifies key challenges to implementing CQI programs
      in community pharmacies and also provides a starting point for future research
      relating to how the challenges of QRE reporting and learning in community
      pharmacies change over time.

PMID- 22421197
TI  - Is newborn melatonin production influenced by magnetic fields produced by
      incubators?
AB  - BACKGROUND: During permanence in most incubators, newborns are very close to the
      electric engine, which represents a source of electromagnetic fields (EMF).
      Previous studies demonstrated a decrease in melatonin production in adults and
      animals exposed to EMF. AIMS: To assess melatonin production in a group of
      newborns exposed to EMF, and to evaluate whether removing the babies from the
      source of MF can affect melatonin production. STUDY DESIGN AND SUBJECTS: We have
      recruited 28 babies (study group), who had spent at least 48 h in incubator where
      we had previously assessed the presence of significant EMF. We have measured
      their mean 6-hydroxy-melatonin-sulfate (6OHMS) urine excretion at the end of
      their permanence in the incubators, and compared it with their mean 6OHMS
      excretion after having been put in cribs, where EMF are below the detectable
      limit (<0.1mG). We have also measured urine 6OHMS twice, with an interval of 48h,
      in a control group of 27 babies who were not exposed to EMF during both samples.
      RESULTS: Mean 6OHMS/cr values were respectively 5.34+/-4.6 and 7.68+/-5.1ng/mg
      (p=0.026) when babies were exposed to EMF in incubators, and after having been
      put in the crib. In the control group, mean 6OHMS/cr values in the first and in
      the second sample were respectively 5.91+/-5.41 vs 6.17+/-3.94ng/mg (p=0.679).
      CONCLUSIONS: The transitory increase in melatonin production soon after removing
      newborns from incubators demonstrates a possible influence of EMF on melatonin
      production in newborns. Further studies are needed to confirm these data.

PMID- 22421198
TI  - Role of cardiopulmonary dysfunction and left atrial remodeling in development of
      acute decompensated heart failure in chronic heart failure with preserved left
      ventricular ejection fraction.
AB  - BACKGROUND: The presence of heart failure (HF) with preserved ejection fraction
      (HFPEF) is increasingly recognized. However, prognostic factors for HFPEF remain
      unclear. METHODS AND RESULTS: The data were derived from Shinken Database 2004
      2010, a prospective cohort study (n=15,227). We examined 301 consecutive HFPEF
      patients (New York Heart Association Class II or greater) and tracked them for an
      average 3.5 years. Cardiopulmonary exercise testing (CPX), blood exams, and
      ultrasound cardiogram (UCG) were performed at the first medical examination.
      Acute decompensated HF (ADHF) admission was observed in 19 patients (6.3%). CPX
      showed that the anaerobic threshold was lower (7.3+/-4.8mL/min/kg vs. 9.7+/
      4.3mL/min/kg, p=0.02) and slope of the increase in ventilation to the increase in
      CO(2) output (VE-VCO(2) slope) was higher (40.6+/-8.5 vs. 34.6+/-7.9, p<0.01) in
      patients with ADHF admission than those without. Serum brain natriuretic peptide
      (BNP) tended to be higher and left atrial (LA) dimension was significantly
      greater (47.0+/-15.8mm vs. 41.0+/-9.9mm, p=0.01) in patients with ADHF admission
      than those without. Multivariate analysis showed that higher VE-VCO(2) slope and
      greater LA dimension were independent determinants of ADHF admission. CONCLUSION:
      An aggravated CPX parameter and LA dilatation were associated with ADHF admission
      in patients with symptomatic HFPEF, suggesting the prognostic role of
      cardiopulmonary dysfunction during exercise and LA remodeling in the pathogenesis
      of decompensated HF development in HFPEF.

PMID- 22421199
TI  - Atomic-resolution imaging in liquid by frequency modulation atomic force
      microscopy using small cantilevers with megahertz-order resonance frequencies.
AB  - In this study, we have investigated the performance of liquid-environment FM-AFM
      with various cantilevers having different dimensions from theoretical and
      experimental aspects. The results show that reduction of the cantilever
      dimensions provides improvement in the minimum detectable force as long as the
      tip height is sufficiently long compared with the width of the cantilever.
      However, we also found two important issues to be overcome to achieve this
      theoretically expected performance. The stable photothermal excitation of a small
      cantilever requires much higher pointing stability of the exciting laser beam
      than that for a long cantilever. We present a way to satisfy this stringent
      requirement using a temperature controlled laser diode module and a polarization
      maintaining optical fiber. Another issue is associated with the tip. While a
      small carbon tip formed by electron beam deposition (EBD) is desirable for small
      cantilevers, we found that an EBD tip is not suitable for atomic-scale
      applications due to the weak tip-sample interaction. Here we show that the tip
      sample interaction can be greatly enhanced by coating the tip with Si. With these
      improvements, we demonstrate atomic-resolution imaging of mica in liquid using a
      small cantilever with a megahertz-order resonance frequency. In addition, we
      experimentally demonstrate the improvement in the minimum detectable force
      obtained by the small cantilever in measurements of oscillatory hydration forces.

PMID- 22421200
TI  - Single-shot dimension measurements of the mouse eye using SD-OCT.
AB  - The authors demonstrate the feasibility and advantage of spectral-domain optical
      coherence tomography (SD-OCT) for single-shot ocular biometric measurement during
      the development of the mouse eye. A high-resolution SD-OCT system was built for
      single-shot imaging of the whole mouse eye in vivo. The axial resolution and
      imaging depth of the system are 4.5 MUm (in tissue) and 5.2 mm, respectively. The
      system is capable of acquiring a cross-sectional OCT image consisting of 2,048
      depth scans in 85 ms. The imaging capability of the SD-OCT system was validated
      by imaging the normal ocular growth and experimental myopia model using C57BL/6J
      mice. The biometric dimensions of the mouse eye can be calculated directly from
      one snapshot of the SD-OCT image. The biometric parameters of the mouse eye
      including axial length, corneal thickness, anterior chamber depth, lens
      thickness, vitreous chamber depth, and retinal thickness were successfully
      measured by the SD-OCT. In the normal ocular growth group, the axial length
      increased significantly from 28 to 82 days of age (P < .001). The lens thickness
      increased and the vitreous chamber depth decreased significantly during this
      period (P < .001 and P = .001, respectively). In the experimental myopia group,
      there were significant increases in vitreous chamber depth and axial length in
      comparison to the control eyes (P = .040 and P < .001, respectively). SD-OCT is
      capable of providing single-shot direct, fast, and high-resolution measurements
      of the dimensions of young and adult mouse eyes. As a result, SD-OCT is a
      potentially powerful tool that can be easily applied to research in eye
      development and myopia using small animal models.

PMID- 22421201
TI  - Evaluation of clear corneal wound dynamics with contrast-enhanced spectral-domain
      optical coherence tomography.
AB  - BACKGROUND AND OBJECTIVE: To evaluate wound morphology and integrity using
      contrast-enhanced spectral-domain optical coherence tomography (SD-OCT). PATIENTS
      AND METHODS: Eighteen patients (18 eyes) undergoing unilateral routine cataract
      surgery were enrolled. SD-OCT imaging of the corneal wound was performed
      immediately following cataract surgery and on postoperative day 1. A topical
      contrast agent, prednisolone acetate 1%, was used to help evaluate wound
      integrity. OCT features of the corneal incision and changes in wound interface
      reflectivity after administration of topical prednisolone acetate 1% were
      analyzed. Main outcome measures were quantitative and qualitative description of
      wound morphology and contrast enhancement of the wound interface. RESULTS:
      Internal wound gape was found in 89% of eyes. Gape area decreased by 43% from
      days 0 to 1 (462 vs 273 MUm(2); P < .01). Contrast enhancement at the wound
      interface was seen in 56% of eyes on day 0 compared to 17% on day 1 following
      application of prednisolone acetate 1% (P < .05). Decreased intraocular pressure
      correlated with increased contrast enhancement (P < .05). CONCLUSION: Wound
      morphology evolves during the early postoperative period. Wound gape and ingress
      of a topical contrast agent decrease during the first 24 hours following surgery.
      Contrast enhancement at the wound interface increases as the intraocular pressure
      decreases.

PMID- 22421202
TI  - Differentiating between conceptual implicit and explicit memory: a crossed double
      dissociation between category-exemplar production and category-cued recall.

PMID- 22421203
TI  - Can an agentic Black woman get ahead? The impact of race and interpersonal
      dominance on perceptions of female leaders.
AB  - Prior research has demonstrated that the display of agentic behaviors, such as
      dominance, can produce backlash against female leaders because of the
      incongruence between these behaviors and prescribed gender roles. The current
      study was designed to fill a gap in existing research by investigating whether
      these well-established findings are moderated by race. Results revealed that
      dominant Black female leaders did not create the same backlash that dominant
      White female leaders did. Experimental evidence confirmed that White female (and
      Black male) leaders were conferred lower status when they expressed dominance
      rather than communality, whereas Black female (and White male) leaders were not.
      These findings highlight the importance, and complexity, of considering the
      intersection of gender and race when examining penalties for and proscriptions
      against dominant behavior of female leaders.

PMID- 22421204
TI  - Do economic equality and generalized trust inhibit academic dishonesty? Evidence
      from state-level search-engine queries.
AB  - What effect does economic inequality have on academic integrity? Using data from
      search-engine queries made between 2003 and 2011 on Google and state-level
      measures of income inequality and generalized trust, I found that academically
      dishonest searches (queries seeking term-paper mills and help with cheating) were
      more likely to come from states with higher income inequality and lower levels of
      generalized trust. These relations persisted even when controlling for contextual
      variables, such as average income and the number of colleges per capita. The
      relation between income inequality and academic dishonesty was fully mediated by
      generalized trust. When there is higher economic inequality, people are less
      likely to view one another as trustworthy. This lower generalized trust, in turn,
      is associated with a greater prevalence of academic dishonesty. These results
      might explain previous findings on the effectiveness of honor codes.

PMID- 22421205
TI  - The persistence of thought: evidence for a role of working memory in the
      maintenance of task-unrelated thinking.
AB  - Tasks that tax working memory (WM) have consistently been found to decrease mind
      wandering. These findings may indicate that maintenance of mind wandering
      requires WM resources, such that mind wandering cannot persist when WM resources
      are being consumed by a task. An alternative explanation for these findings,
      however, is that mind wandering persists without the support of WM but is
      nonetheless decreased during any demanding task because good task performance
      requires that attention be restricted from task-unrelated thought (TUT). The
      present study tested these two competing theories by investigating whether
      individuals with greater WM resources mind-wander more during an undemanding
      task, as would be predicted only by the theory that WM supports TUT. We found
      that individuals with higher WM capacity reported more TUT in undemanding tasks,
      which suggests that WM enables the maintenance of mind wandering.

PMID- 22421206
TI  - New generation QuIC assays for prion seeding activity.
AB  - The ability of abnormal TSE-associated forms of PrP to seed the formation of
      amyloid fibrils from recombinant PrP(Sen) has served as the basis for several
      relatively rapid and highly sensitive tests for prion diseases. These tests
      include rPrP-PMCA (rPMCA), standard quaking-induced conversion (S-QuIC), amyloid
      seeding assay (ASA), real-time QuIC (RT-QuIC) and enhanced QuIC (eQuIC). Here, we
      summarize recent improvements in the RT-QuIC-based assays that enhance the
      practicality, sensitivity and quantitative attributes of assays QuIC and promote
      the detection of prion seeding activity in dilute, inhibitor-laden fluids such as
      blood plasma.

PMID- 22421207
TI  - Disease phenotype in sheep after infection with cloned murine scrapie strains.
AB  - Prion diseases exhibit different disease phenotypes in their natural hosts and
      when transmitted to rodents, and this variability is regarded as indicative of
      prion strain diversity. Phenotypic characterization of scrapie strains in sheep
      can be attempted by histological, immunohistochemical and biochemical approaches,
      but it is widely considered that strain confirmation and characterization
      requires rodent bioassay. Examples of scrapie strains obtained from original
      sheep isolates by serial passage in mice include ME7, 79A, 22A and 87V. In order
      to address aspects of prion strain stability across the species barrier, we
      transmitted the above murine strains to sheep of different breeds and susceptible
      Prnp genotypes. The experiment included 40 sheep dosed by the oral route alone
      and 36 sheep challenged by combined subcutaneous and intracerebral routes.
      Overall, the combined route produced higher attack rates (~100%) than the oral
      route (~50%) and 2-4 times shorter incubation periods. Uniquely, 87V given orally
      was unable to infect any sheep. Overall, scrapie strains adapted and cloned in
      mice produce distinct but variable disease phenotypes in sheep depending on breed
      or Prnp genotype. Further re-isolation experiments in mice are in progress in
      order to determine whether the original cloned murine disease phenotype will
      reemerge.

PMID- 22421208
TI  - Aggregated proteins in schizophrenia and other chronic mental diseases:
      DISC1opathies.
AB  - Chronic mental diseases (CMD) like the schizophrenias are progressive diseases of
      heterogenous but poorly understood biological origin. An imbalance in
      proteostasis is a hallmark of dysfunctional neurons, leading to impaired
      clearance and abnormal deposition of protein aggregates. Thus, it can be
      hypothesized that unbalanced proteostasis in such neurons may also lead to
      protein aggregates in schizophrenia. These protein aggregates, however, would be
      more subtle then in the classical neurodegenerative diseases and as such have not
      yet been detected. The DISC1 (Disrupted-in-schizophrenia 1) gene is considered
      among the most promising candidate genes for CMD having been identified as linked
      to CMD in a Scottish pedigree and having since been found to associate to various
      phenotypes of CMD. We have recently demonstrated increased insoluble DISC1
      protein in the cingular cortex in approximately 20% of cases of CMD within the
      widely used Stanley Medical Research Institute Consortium Collection.
      Surprisingly, in vitro, DISC1 aggregates were cell-invasive, i.e., purified
      aggresomes or recombinant DISC1 fragments where internalized at an efficiency
      comparable to that of alpha-synuclein. Intracellular DISC1 aggresomes acquired
      gain-of-function properties in recruiting otherwise soluble proteins such as the
      candidate schizophrenia protein dysbindin. Disease-associated DISC1 polymorphism
      S704C led to a higher oligomerization tendency of DISC1. These findings justify
      classification of DISC1-dependent brain disorders as protein conformational
      disorders which we have tentatively termed DISC1opathies. The notion of disturbed
      proteostasis and protein aggregation as a mechanism of mental diseases is thus
      emerging. The yet unidentified form of neuronal impairment in CMD is more subtle
      than in the classical neurodegenerative diseases without leading to massive cell
      death and as such present a different kind of neuronal dysfunctionality,
      eventually confined to highly selective CNS subpopulations.

PMID- 22421209
TI  - The diverse roles of mononuclear phagocytes in prion disease pathogenesis.
AB  - Transmissible spongiform encephalopathies (TSEs), or prion diseases, are
      neurological diseases that can be transmitted through a number of different
      routes. A wide range of mammalian species are affected by the disease. After
      peripheral exposure, some TSE agents accumulate in lymphoid tissues at an early
      stage of disease prior to spreading to the nerves and the brain. Much research
      has focused on identifying the cells and molecules involved in the transmission
      of TSE agents from the site of exposure to the brain and several crucial cell
      types have been associated with this process. The identification of the key cells
      that influence the different stages of disease transmission might identify
      targets for therapeutic intervention. This review highlights the involvement of
      mononuclear phagocytes in TSE disease. Current data suggest these cells may
      exhibit a diverse range of roles in TSE disease from the transport or destruction
      of TSE agents in lymphoid tissues, to mediators or protectors of neuropathology
      in the brain.

PMID- 22421211
TI  - Nanopore analysis: An emerging technique for studying the folding and misfolding
      of proteins.
AB  - Nanopore analysis is an emerging technique that enables the investigation of the
      conformation of a single peptide or protein molecule. Briefly, a pore is inserted
      into a membrane under voltage clamp conditions. When a molecule interacts with
      the pore there is a change in the current, I, for a time, T. Small unfolded
      molecules can translocate the pore whereas folded or large molecules tend to
      simply bump into the pore and then diffuse away. Therefore, the parameters, I and
      T, are dependent on the conformation of the molecule at the instant at which it
      encounters the pore. Thus, multiple conformations can be detected simultaneously
      in a single sample. As well, the analysis can be performed under dilute
      conditions so that folding or dimerization of a peptide can be followed in real
      time, which is generally difficult to study for proteins that are prone to
      aggregate. In this report, we describe our initial analysis of (1) Abeta
      peptides, which are deposited as amyloid plaques in Alzheimer disease, (2) alpha
      synuclein, which is implicated in Parkinson disease and (3) prion proteins whose
      misfolding is evident in transmissable spongiform encephalopathies. In each case
      conformational information can be obtained which may help in understanding the
      early steps in the misfolding pathways.

PMID- 22421212
TI  - Phylogeny of Bembidion and related ground beetles (Coleoptera: Carabidae:
      Trechinae: Bembidiini: Bembidiina).
AB  - The phylogeny of the large genus Bembidion and related genera is inferred from
      four nuclear protein-coding genes (CAD, wingless, arginine kinase, and
      topoisomerase I), ribosomal DNA (28S and 18S), and the mitochondrial gene
      cytochrome oxidase I (COI). 230 of the more than 1200 species of Bembidion are
      sampled, as well as 26 species of five related genera, and 14 outgroups. Nuclear
      copies (numts) of COI were found sparsely scattered through sampled species. The
      resulting phylogeny, based upon individual gene analyses and combined analyses
      using maximum likelihood and parsimony, is very well supported at most nodes.
      Additional analyses explored the evidence, and corroborate the phylogeny. Seven
      analyses, each with one of the seven genes removed from the combined matrix, were
      also conducted, and yielded maximum likelihood bootstrap trees sharing over 92%
      of their nodes with the original, well-resolved bootstrap trees based on the
      complete set of seven genes. All key nodes were present in all seven analyses
      missing a single gene, indicating that support for these nodes comes from at
      least two genes. In addition, the inferred maximum likelihood tree based on the
      combined matrix is well-behaved and self-predicting, in that simulated evolution
      of sequences on the inferred tree under the inferred model of evolution yields a
      matrix from which all but one of the model tree's clades are recovered with
      bootstrap value >50, suggesting that internal branches in the tree may be of a
      length to yield sequences sufficient to allow their inference. All likelihood
      analyses were conducted under both a proportion-invariable plus gamma site-to
      site rate variation model, as well as a simpler gamma model. The choice of model
      did not have a major effect on inferred phylogenies or their bootstrap values.
      The inferred phylogeny shows that Bembidarenas is not closely related to
      Bembidiina, and Phrypeus is likely distant as well; the remaining genera of
      Bembidiina form a monophyletic group. Lionepha, formerly considered a subgenus of
      Bembidion, is shown to be outside of the clade of Asaphidion+Bembidion, and is
      separated as its own genus. B. (Phyla) obtusum is quite isolated within
      Bembidion, and there is some evidence that the remaining Bembidion form a clade.
      Within Bembidion, there are three large clades that are well-supported, the
      Bembidion, Odontium, and Ocydromus Series. The Bembidion Series contains
      Bembidion (s. str.), Notaphus, Furcacampa, Emphanes, Trepanedoris, Diplocampa,
      and related Holarctic species; all species from South America, Australia, New
      Zealand; and most species from southern Africa and Madagascar. All species in
      South America, except for members of Notaphus and Nothocys, form a clade, the
      Antiperyphanes Complex, which has independently radiated into body forms and
      niches occupied by multiple, independent Northern-Hemisphere forms. All species
      from New Zealand, including Zecillenus, and Australian species formerly placed in
      Ananotaphus together form a clade. Bembidion (s. str.) and Cyclolopha are in a
      clade with the Old World, Southern Hemisphere lineages Notaphocampa, Sloanephila,
      and Omotaphus. The large subgenus Notaphus appears to have originated in South
      America, with all Northern Hemisphere Notaphus arising from within a south
      temperate grade. All major variation in frontal furrows on the head is contained
      within the Bembidion Series. The Odontium Series contains subgenera
      Hirmoplataphus and Hydriomicrus, which together are the sister clade of Odontium,
      Bracteon, Ochthedromus, Pseudoperyphus, and Microserrullula. The very large
      Ocydromus Series, dominant in the Holarctic region, includes the Ocydromus
      Complex, with many subgenera, including Hypsipezum and Leuchydrium; the phylogeny
      within this group is notably at odds with the current classification. Also
      included in the Ocydromus Series are Nepha and Bembidionetolitzkya, as well as
      the Princidium Complex, in which the intertidal B. (Cillenus) laterale falls.
      Outside these three series are a number of smaller groups, including the
      Plataphus Complex (containing Blepharoplataphus, Plataphus, the latter including
      Plataphodes); the Hydrium Complex (Metallina, Chlorodium, and Hydrium, which
      contains Eurytrachelus), whose sister group might be subgenus Andrewesa;
      Trechonepha and Liocosmius, which might be sisters; and B. (Melomalus) planatum,
      which is not close to Plataphus. There is some evidence that these groups plus
      the Ocydromus and Odontium Series form a clade. A few enigmatic groups were
      harder to place. The sister group of the pair Philochthus plus Philochthemphanes
      might be B. wickhami; Eupetedromus is well outside the three major series and not
      related to Notaphus; the high-elevation Asian group Hoquedela is a very isolated
      lineage. Notaphiellus is removed from synonymy with Nothocys, and placed in
      synonymy with Notaphus; Plataphodes is synonymized with Plataphus, as Plataphus
      is paraphyletic otherwise; Eurytrachelus is synonymized with Hydrium. A new
      subgenus, Lindrochthus, is described to house the distinctive B. wickhami. The
      implications of the inferred phylogeny for some morphological characters used in
      Bembidiina systematics are explored, and some of the most widely used (e.g.,
      location of discal seta ed3 on the elytron, and shape of the shoulder) are shown
      to be notably homoplastic. For example, the location of elytral seta ed3 has
      undergone at least nine transitions between two states.

PMID- 22421210
TI  - Molecular pathogenesis of sporadic prion diseases in man.
AB  - The yeast, fungal and mammalian prions determine heritable and infectious traits
      that are encoded in alternative conformations of proteins. They cause lethal
      sporadic, familial and infectious neurodegenerative conditions in man, including
      Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS),
      kuru, sporadic fatal insomnia (SFI) and likely variable protease-sensitive
      prionopathy (VPSPr). The most prevalent of human prion diseases is sporadic
      (s)CJD. Recent advances in amplification and detection of prions led to
      considerable optimism that early and possibly preclinical diagnosis and therapy
      might become a reality. Although several drugs have already been tested in small
      numbers of sCJD patients, there is no clear evidence of any agent's efficacy.
      Therefore, it remains crucial to determine the full spectrum of sCJD prion
      strains and the conformational features in the pathogenic human prion protein
      governing replication of sCJD prions. Research in this direction is essential for
      the rational development of diagnostic as well as therapeutic strategies.
      Moreover, there is growing recognition that fundamental processes involved in
      human prion propagation - intercellular induction of protein misfolding and
      seeded aggregation of misfolded host proteins - are of far wider significance.
      This insight leads to new avenues of research in the ever-widening spectrum of
      age-related human neurodegenerative diseases that are caused by protein
      misfolding and that pose a major challenge for healthcare.

PMID- 22421213
TI  - Species delimitation and cryptic diversity in the moss genus Scleropodium
      (Brachytheciaceae).
AB  - Cryptic lineage diversification is an important component of global biodiversity,
      but it presents challenges to our ability to catalog and understand that
      diversity. Because of their relative morphological simplicity and broad
      geographic distributions, bryophytes are an ideal study group for investigating
      this phenomenon. This study generated molecular data from 109 ingroup individuals
      to test morphological species circumscriptions and examine patterns of cryptic
      lineage diversification within the small north temperate moss genus Scleropodium
      (Brachytheciaceae). Maximum Parsimony and Bayesian phylogenetic analyses and
      statistical parsimony network analyses of ITS and chloroplast rps4, psbA2 and
      trnG regions indicate that the genus comprises six distinct molecular groups.
      Five of these molecular groups correspond to previously recognized species: S.
      californicum (Lesq.) Kindb., S. cespitans (Mull.) Koch, S. julaceum Lawton, S.
      obtusifolium (Mitt.) Kindb. in Macoun and S. touretii Brid. (Koch). However, the
      sixth group does not correspond to any existing species. Maximum parsimony and
      Bayesian posterior probability support for the monophyly of species varied widely
      and depended on both the dataset (ITS, chloroplast, combined) and the analysis
      method (Parsimony/Bayesian). Low phylogenetic resolution of species is
      attributable to the lack of informative DNA sequence vaiation and incongruent
      placements of three accessions in the chloroplast and ITS gene trees, both
      suggesting recent divergence within the genus. Re-examination of the herbarium
      vouchers for the sixth molecular group reveals that they form a group nested
      within the morphological circumscription of S. obtusifolium. One subtle
      morphological character (relative frequency of a costa spine) was identified that
      has utility in discriminating these two genetically distinct but morphologically
      very similar species.

PMID- 22421214
TI  - [Strengths and weaknesses of a cervical cancer detection and control program: a
      qualitative evaluation in San Luis Potosi, Mexico].
AB  - OBJECTIVE: To identify, from the perspective of the health staff, the strengths
      and weaknesses of the program for the detection and control of cervical cancer
      through a qualitative assessment implemented in three health centers in the city
      of San Luis Potosi, Mexico, from August 2008 to November 2009. METHODS: A
      qualitative evaluation was performed. Nine providers participated in the study.
      The providers were selected by purposeful sampling using a voluntary
      participation criterion. Initially, information on the characteristics and the
      context in which the program operates was obtained from the health centers.
      Later, 18 semi-structured interviews were conducted with nine informants to probe
      their perspective. A directed content analysis was used. RESULTS: The strengths
      reported by staff were the fact that the program is free of charge, the
      availability of material resources, and the strategies that helped encourage the
      recruitment of women and their access to screening. The main weaknesses consisted
      of limitations in human resources and physical infrastructure, inefficient
      organization of activities, the staff's poor technical training, limited
      promotion of activities, and limitations in monitoring women with positive
      results. CONCLUSIONS: This study reveals the need for increased human resources,
      changes in regulations and reorganization of the program's actions in some health
      centers to ensure the quality of the service, meet women's needs, and promote
      coverage in all the program's actions.

PMID- 22421215
TI  - Incidence of nonunion of first metatarsophalangeal joint arthrodesis for severe
      hallux valgus using crossed, flexible titanium intramedullary nails and a dorsal
      static staple with immediate weightbearing in female patients.
AB  - Myriad forms of fixation have been proposed for arthrodesis of the first
      metatarsophalangeal joint (MTPJ). Regardless of fixation type, nonunion of the
      arthrodesis site has been purported as a common complication. The authors
      performed a retrospective analysis of all patients undergoing arthrodesis of the
      first MTPJ for severe hallux valgus with 2 crossed, flexible titanium
      intramedullary nails and a dorsal static 10-mm titanium staple followed by
      immediate protected weightbearing. Patients were included if they had: surgery
      for severe hallux valgus of the first MTPJ; undergone the exact internal fixation
      technique described; not undergone bilateral surgery in the same setting;
      weightbearing preoperative radiographs; at least 6-week postoperative
      weightbearing radiographs; initiated weightbearing on the operative foot
      immediately postoperative in a protective shoe; been followed up clinically for
      at least 6 months' time postoperatively; and documentation of any complications.
      One hundred fifty-six female patients (195 feet) with a mean age of 67 +/- 9.3
      years met the inclusion criteria. Complications due to technical error during
      insertion of the crossed, flexibe titanium intramedullary nails occurred in 22
      (11.3%) feet, but none led to revision surgery. There were 5 (2.6%) asymptomatic
      nonunions and 1 (0.5%) delayed union, but this ultimately united. The incidence
      of nonunion after arthrodesis of the first MTPJ using the specific internal
      fixation construct presented here for severe hallux valgus is lower than the
      historic mean for most other fixation techniques. However, there is still a need
      for methodologically sound prospective cohort studies that compare the technique
      presented here with other modern osteosynthesis techniques.

PMID- 22421216
TI  - The effect of functionalization of mesoporous silica nanoparticles on the
      interaction and stability of confined enzyme.
AB  - Immobilization of enzymes into the mesoporous nanomaterials results in formation
      of more stable and even more active versions of biocatalysts. The effect of
      surface functionalization of mesoporous silica nanoparticles (MSNs) on its
      adsorption characteristics and stability of superoxide dismutase (SOD) was
      investigated. For this purpose, non-functionalized (KIT-6) and aminopropyl
      functionalized cubic Ia3d mesoporous silica ([n-PrNH(2)-KIT-6]) nanoparticles
      with 3-dimensional pores were used as supports. It was observed that the amount
      of enzyme adsorbed on/within MSNs is dependent on the initial enzyme
      concentration for both KIT-6 and [n-PrNH(2)-KIT-6] mesoporous silicas. However a
      stronger interaction between SOD and [n-PrNH(2)-KIT-6] was observed relative to
      KIT-6. Increasing temperature favors a larger amount of SOD immobilization into
      KIT-6, while it was negligible for [n-PrNH(2)-KIT-6]. Immobilized SOD was more
      stable against urea and thermal denaturation relative to free enzyme and this
      improvement of stability was more pronounced for SOD into the [n-PrNH(2)-KIT-6]
      than KIT-6. These results may be useful in determining the mechanism(s) of
      protein immobilization and stabilization into the solid supports.

PMID- 22421217
TI  - Thermal disaggregation of type B yeast hexokinase by indole derivatives: a
      mechanistic study.
AB  - Protein aggregation is a pathological hallmark of several human disorders, and a
      central problem in biotechnology, occurring during purification, sterilization,
      shipping and storage of protein structures. The process is a very complex one,
      characterized with a remarkable polymorphism of aggregates, including soluble
      amyloid oligomers, amyloid fibrils and amorphous species. While amyloid structure
      formation has been extensively investigated during the recent years, amorphous
      aggregation is still not well characterized. Use of small molecules that affect
      this process could be informative in this regard. In order to explore the
      inhibiting effect of small molecules on the amorphous aggregate formation, yeast
      hexokinase-B, a key enzyme in metabolism, has been chosen for the present study.
      Thermal aggregation of the enzyme was investigated in 50 mM phosphate buffer, pH
      7 at 55 degrees C and the extent of aggregation was measured by monitoring the
      increase in absorbance at 350 nm versus time. Possible anti-aggregation effects
      of a variety of non-specific ligands including indole, tryptophan, carbinol, and
      indomethacin were explored. Turbidity of the protein solutions was found to be
      diminished by the presence of these small molecules in the above conditions, with
      the highest effects being exerted by indomethacin. Dynamic light scattering and
      HPLC confirmed that indomethacin had the highest anti-aggregation effect. These
      observations, taken together, suggest that the indole ring is likely to play an
      important role in aggregation inhibition.

PMID- 22421218
TI  - Smad7 sensitizes A549 lung cancer cells to cisplatin-induced apoptosis through
      heme oxygenase-1 inhibition.
AB  - Smad7, an inhibitory Smad, acts as a key regulator forming autoinhibitory
      feedback loop in transforming growth factor-beta (TGF-beta) signaling. However, a
      growing body of evidences suggests that Smad7 is capable of apoptotic function.
      In the present study, we have demonstrated a proapoptotic function of Smad7 as a
      negative regulator of survival protein heme oxygenase-1 (HO-1). The HO-1 protein
      level was elevated in cisplatin-resistant A549 human lung cancer cells and
      blockade of HO-1 activation sensitized the cells to apoptosis. Interestingly,
      overexpression of Smad7 decreased HO-1 gene expression and its enzymatic
      activity. Notably, Smad7 reduced Akt activity and infection with adenovirus
      expressing a constitutively active form of the Akt reversed the inhibitory
      effects of Smad7 to HO-1, indicating a negative action mechanism of Smad7 to Akt
      HO-1-linked survival pathway. Consistently, Smad7 sensitized A549 cells to
      cisplatin-induced apoptosis and these effects were dependent on HO-1 and Akt
      inhibition. Based on these findings, we suggest that targeting Smad7 may be an
      efficient strategy for overcoming drug-resistance in cancer therapy.

PMID- 22421219
TI  - BMP signaling is responsible for serum-induced Id2 expression.
AB  - Ids function as negative regulators of basic helix-loop-helix transcription
      factors and their expression is rapidly induced by serum stimulation in various
      cell types. In this study, we investigated the molecular basis of serum-induced
      expression of the mouse Id2 gene in NIH3T3 cells. A small-molecule inhibitor of
      bone morphogenetic protein (BMP) type I receptor kinases blocked the serum
      induction of Id2 mRNA. The chemical compound and several inhibitory proteins
      specific for BMP signaling suppressed the serum-induced activation of the
      luciferase construct with the mouse Id2 4.6-kb promoter region. Importantly,
      serum stimulation evoked rapid phosphorylation of Smad1/5/8 and significant
      activation of the reporter plasmid containing the recently identified BMP
      responsive element (BRE) of the mouse Id2. Mutation analysis demonstrated that
      the binding sites for Smad proteins in the Id2 BRE were critical for serum
      response of the 4.6-kb whole construct. Gel shift and chromatin
      immunoprecipitation (ChIP) assays confirmed the serum-inducible binding of
      Smad1/5/8 and Smad4 to the Id2 BRE in vitro and in vivo. Finally, a knockdown
      experiment revealed the functional importance of Smad1 in the serum induction of
      Id2 expression. Thus, we concluded that BMP signaling is primarily responsible
      for the serum-induced Id2 expression. Our results also suggest that some of the
      cellular effects caused by serum are mediated through BMP signaling.

PMID- 22421220
TI  - Motivation and timing: clues for modeling the reward system.
AB  - There is growing evidence that a change in reward magnitude or value alters
      interval timing, indicating that motivation and timing are not independent
      processes as was previously believed. The present paper reviews several recent
      studies, as well as presenting some new evidence with further manipulations of
      reward value during training vs. testing on a peak procedure. The combined
      results cannot be accounted for by any of the current psychological timing
      theories. However, in examining the neural circuitry of the reward system, it is
      not surprising that motivation has an impact on timing because the
      motivation/valuation system directly interfaces with the timing system. A new
      approach is proposed for the development of the next generation of timing models,
      which utilizes knowledge of the neuroanatomy and neurophysiology of the reward
      system to guide the development of a neurocomputational model of the reward
      system. The initial foundation along with heuristics for proceeding with
      developing such a model is unveiled in an attempt to stimulate new theoretical
      approaches in the field.

PMID- 22421221
TI  - An assessment of Gallistel's (2012) rationalistic account of extinction
      phenomena.
AB  - Gallistel (2012) asserts that animals use rationalistic reasoning (i.e.,
      information theory and Bayesian inference) to make decisions that underlie select
      extinction phenomena. Rational processes are presumed to lead to evolutionarily
      optimal behavior. Thus, Gallistel's model is a type of optimality theory. But
      optimality theory is only a theory, a theory about an ideal organism, and its
      predictions frequently deviate appreciably from observed behavior of animals in
      the laboratory and the real world. That is, behavior of animals is often far from
      optimal, as is evident in many behavioral phenomena. Hence, appeals to optimality
      theory to explain, rather than illuminate, actual behavior are misguided.

PMID- 22421222
TI  - Definitions and methodology for the grayscale and radiofrequency intravascular
      ultrasound and coronary angiographic analyses.
AB  - OBJECTIVES: In a prospective study of the natural history of coronary
      atherosclerosis using angiography and grayscale and radiofrequency intravascular
      ultrasound (IVUS)-virtual histology (VH), larger plaque burden, smaller luminal
      area, and plaque composition thin-cap fibroatheroma emerged as independent
      predictors of future adverse cardiovascular events. BACKGROUND: The methodology
      for IVUS-VH classification for an in vivo natural history study and the
      prospective image mapping by angiography and grayscale and IVUS-VH have not been
      established. METHODS: All culprit and nonculprit lesions (defined as >= 30%
      angiographic visual diameter stenoses) were analyzed. Three epicardial vessels as
      well as all >= 1.5-mm-diameter side branches were divided into 29 CASS (Coronary
      Artery Surgery Study) segments. Each CASS segment was then subdivided into 1.5-mm
      long subsegments, and dimensions were analyzed. All grayscale and IVUS-VH slices
      from the proximal 6 to 8 cm of the 3 coronary arteries were analyzed, with
      lesions defined as having more than 3 consecutive slices with >= 40% plaque
      burden categorized as: 1) VH thin-cap fibroatheroma; 2) thick-cap fibroatheroma;
      3) pathological intimal thickening; 4) fibrotic plaque; or 5) fibrocalcific
      plaque. The locations of angiographic and grayscale and IVUS-VH lesions were
      recorded in relation to the corresponding coronary artery ostium and nearby side
      branches. RESULTS: The 3-year cumulative rate of major adverse cardiovascular
      events was 20.4%. Events were adjudicated to culprit lesions in 12.9% of patients
      and to nonculprit lesions in 11.6%. On multivariate analysis, nonculprit lesions
      associated with recurrent events were characterized by a plaque burden >= 70%
      (hazard ratio: 5.03; 95% confidence interval: 2.51 to 10.11; p < 0.0001), a
      minimal luminal area <= 4.0 mm(2) (hazard ratio: 3.21; 95% confidence interval:
      1.61 to 6.42; p = 0.001), and IVUS-VH phenotype of a thin-cap fibroatheroma
      (hazard ratio: 3.35; 95% confidence interval: 1.77 to 6.36; p < 0.001).
      CONCLUSIONS: Three-vessel multimodality coronary artery imaging was feasible and
      allowed the identification of lesion-level predictors for future events in this
      natural history study.

PMID- 22421223
TI  - Longitudinal distribution of plaque burden and necrotic core-rich plaques in
      nonculprit lesions of patients presenting with acute coronary syndromes.
AB  - OBJECTIVES: In this substudy of the PROSPECT (Providing Regional Observations to
      Study Predictors of Events in the Coronary Tree) study, we examined the
      longitudinal distribution of atherosclerotic plaque burden, virtual histology
      intravascular ultrasound (VH-IVUS) characterized necrotic core (NC) content and
      VH-thin-cap fibroatheroma (TCFA) distribution in nonculprit lesions of patients
      presenting with acute coronary syndromes. BACKGROUND: Previous analyses suggested
      that vulnerable plaques and acute myocardial infarction may occur more frequently
      in the proximal than the distal coronary tree. METHODS: A total of 4,234
      proximal, mid, and distal 30-mm-long segments of each epicardial coronary artery
      were compared with each other and to the left main coronary artery (LMCA).
      RESULTS: Combining IVUS data from all 3 arteries, there was a gradient in plaque
      burden from the proximal (42.4%) to mid (37.6%) to distal (32.6%) 30-mm-long
      segments (p < 0.0001). Overall, 67.4% of proximal, 41.0% of mid, and 29.7% of
      distal 30-mm-long segments contained at least 1 lesion (plaque burden >40%).
      Proportion of NC, however, was similar in the proximal and mid 30-mm-long
      segments of all arteries (10.3% [interquartile range (IQR): 4.8% to 16.7%] vs.
      10.6% [IQR: 5.0% to 18.1%], p = 0.25), but less in the distal 30-mm-long segment
      (9.1% [IQR: 3.7% to 17.8%], p = 0.03 compared with the proximal segment and p =
      0.003 compared with the mid segment). Overall, 17.3% of proximal, 11.5% of mid,
      and 9.1% of distal 30-mm-long segments had at least 1 lesion that was classified
      as VH-TCFA (p < 0.0001). Comparing the LMCA with the combined cohort of proximal
      left anterior descending, left circumflex, and right coronary artery 30-mm-long
      segments: 1) plaque burden was less (35.4% [IQR: 28.8% to 43.5%] vs. 40.9% [IQR:
      33.3% to 48.0%], p < 0.0001); 2) fewer LMCAs contained at least 1 lesion (17.5%,
      p < 0.0001); 3) there was less NC (6.5% [IQR: 2.9% to 12.2%] vs. 9.3% [IQR: 4.3%
      to 15.9%], p < 0.0001); and 4) LMCAs rarely contained a VH-TCFA (1.8%, p <
      0.0001). CONCLUSIONS: The current analysis appears to confirm that lesions that
      are responsible for acute coronary events (large, plaque burden-rich in NC) are
      somewhat more likely to be present in the proximal than the distal coronary tree,
      except for the LMCA.

PMID- 22421224
TI  - Improved prospects for IVUS in identifying vulnerable plaques?

PMID- 22421225
TI  - Plaque composition by intravascular ultrasound and distal embolization after
      percutaneous coronary intervention.
AB  - Distal embolization after percutaneous coronary intervention occurs in 15% to 70%
      of patients, depending on the sensitivity of the diagnostic modality used, and is
      associated with a poor prognosis after elective and primary percutaneous coronary
      intervention. It has been hypothesized that imaging of the plaque composition can
      identify coronary artery lesions that are predisposed to causing distal
      embolization. This review report aims to summarize all currently available
      published data on the use of assessment of atherosclerotic plaque composition by
      virtual histology intravascular ultrasound (VH-IVUS) to predict the occurrence of
      distal embolization. A systematic review of the literature was performed. We
      searched Medline, ISI Web of Knowledge, and the Cochrane Library from January
      2002 until March 2011. When a study was found to be relevant, the manuscript was
      obtained and reviewed. A total of 11 studies were identified investigating the
      relationship between plaque composition assessed by VH-IVUS and distal
      embolization. Although all studies used the same equipment to perform and analyze
      VH-IVUS, there was considerable heterogeneity in patient characteristics, outcome
      definitions, and reporting of VH-IVUS findings. Nevertheless, the necrotic core
      plaque component-either by itself or as a constituent of a VH thin cap
      fibroatheroma-was associated with distal embolization in all but 2 of the 11
      reviewed studies. Therefore, identification of lesions with large amounts of
      necrotic core on VH-IVUS could identify lesions that might benefit from the
      selective use of embolic protection devices.

PMID- 22421226
TI  - Plaque compositional Syntax score: combining angiography and lipid burden in
      coronary artery disease.

PMID- 22421227
TI  - Relationship between palpography and virtual histology in patients with acute
      coronary syndromes.
AB  - OBJECTIVES: The purpose of this study was to correlate adverse events at long
      term follow-up in patients after an acute coronary syndrome with coronary plaque
      characteristics derived from simultaneous evaluation of their mechanical and
      compositional properties using virtual histology (intravascular ultrasound
      virtual histology) and palpography. BACKGROUND: Fibroatheroma is the plaque
      morphology with the highest risk of causing adverse cardiac events. Palpography
      can potentially assess the local mechanical plaque properties with the
      possibility of identifying fibroatheroma with the highest risk of rupture.
      METHODS: A total of 114 patients with acute coronary syndrome from the PROSPECT
      (Providing Regional Observations to Study Predictors of Events in the Coronary
      Tree) trial underwent a single ultrasound imaging investigation of their 3
      coronary vessels with the co-registration of intravascular ultrasound virtual
      histology and palpography. Major adverse cardiac events (MACE) (cardiac death,
      cardiac arrest, myocardial infarction, or unstable or progressive angina) were
      collected up to a median follow-up of 3.4 years and adjudicated to originally
      treated culprit versus untreated nonculprit lesions. RESULTS: In total, 488
      necrotic core-rich plaques were identified and subclassified as thin-cap
      fibroatheroma (n = 111), calcified thick-cap fibroatheroma (n = 213), and
      noncalcified thick-cap fibroatheroma (n = 164) and matched to their co-registered
      palpography data. A total of 16 MACE, adjudicated to untreated nonculprit
      lesions, were recorded at follow-up. In patients in whom MACE developed,
      fibroatheroma were larger (plaque area 10.0 mm(2) [range: 8.4 to 11.6 mm(2)] vs.
      8.2 mm(2) [range: 7.7 to 8.8 mm(2)] (p = 0.03) compared with patients who were
      MACE free. By palpography, the maximum and the density strain values did not
      differ between the varying subtypes of fibroatheroma of patients with or without
      MACE during follow-up. CONCLUSIONS: In acute coronary syndromes, patients treated
      with stents and contemporary pharmacotherapy, palpography did not provide
      additional diagnostic information for the identification of fibroatheroma with a
      high risk of rupture and MACE during long-term follow-up. (Providing Regional
      Observations to Study Predictors of Events in the Coronary Tree [PROSPECT]: An
      Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466).

PMID- 22421228
TI  - Natural history of coronary atherosclerosis by multislice computed tomography.
AB  - OBJECTIVES: This study sought to analyze the natural history of coronary
      atherosclerosis by multislice computed tomography (MSCT) and assess the serial
      changes in coronary plaque burden, lumen dimensions, and arterial remodeling.
      BACKGROUND: MSCT can comprehensively assess coronary atherosclerosis by combining
      lumen and plaque size parameters. METHODS: Thirty-two patients with acute
      coronary syndromes underwent 64-slice computed tomography angiography after
      percutaneous coronary intervention at baseline and after a median of 39 months.
      All patients received contemporary medical treatment. All available coronary
      segments in every subject were analyzed. The progression of atherosclerosis per
      segment and per patient was assessed by means of change in percent atheroma
      volume (PAV), change in normalized total atheroma volume (TAVnorm), and percent
      change in TAV (% change in TAV). Serial coronary remodeling was also assessed.
      Measures of lumen stenosis included percent diameter stenosis (%DS), minimum
      lumen diameter (MLD), percent area stenosis (%AS), and minimum lumen area (MLA).
      For each patient, the mean of all matched segments was calculated at the 2 time
      points. Clinical events at follow-up were documented. RESULTS: The PAV did not
      change significantly (-0.15 +/- 3.64%, p = 0.72). The mean change in TAVnorm was
      47.36 +/- 143.24 mm(3) (p = 0.071), and the % change in TAV was 6.7% (p = 0.029).
      The MLD and MLA increased by 0.15 mm (-0.09 to 0.24, p = 0.039) and 0.52 mm(2) (
      0.38 to 1.04, p = 0.034) respectively, which was accompanied by vessel
      enlargement, with 53% of the patients showing expansive positive remodeling.
      Patients with clinical events had a larger TAVnorm at baseline (969.72 mm(3) vs.
      810.77 mm(3), p = 0.010). CONCLUSIONS: MSCT can assess the progression of
      coronary atherosclerosis and may be used for noninvasive monitoring of
      pharmacological interventions in coronary artery disease. ( PROSPECT: An Imaging
      Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466).

PMID- 22421229
TI  - Prediction of coronary events by intravascular imaging.

PMID- 22421230
TI  - Plaque composition and clinical outcomes in acute coronary syndrome patients with
      metabolic syndrome or diabetes.
AB  - OBJECTIVES: The goal of this study was to characterize the extent and composition
      of coronary atherosclerosis in patients with diabetes mellitus or the metabolic
      syndrome (Met Syn) presenting with acute coronary syndromes (ACS). BACKGROUND:
      Diabetes and Met Syn patients have increased rates of major adverse cardiac
      events (MACE), yet a systematic description of nonculprit lesions for these high
      risk groups is incomplete. METHODS: In the PROSPECT (Providing Regional
      Observations to Study Predictors of Events in the Coronary Tree) study, ACS
      patients underwent 3-vessel quantitative coronary angiography, grayscale, and
      radiofrequency intravascular ultrasound after successful percutaneous coronary
      intervention (PCI). Subsequent MACE (cardiac death or arrest, myocardial
      infarction, or rehospitalization for unstable or progressive angina) were
      adjudicated to the originally treated culprit versus untreated nonculprit lesions
      in 3 patient groups: 1) diabetes; 2) Met Syn; and 3) neither. Median length of
      follow-up was 3.4 years. RESULTS: Of 673 patients, 119 (17.7%) had diabetes and
      239 (35.5%) had Met Syn. The cumulative 3-year MACE rate was 29.4% in patients
      with diabetes, 21.3% with Met Syn, and 17.4% with neither (p = 0.03). MACE
      adjudicated to untreated nonculprit lesions occurred in 18.7%, 11.7%, and 9.7% of
      patients, respectively (p = 0.06). Nonculprit lesions in diabetes and Met Syn
      patients were longer and had greater plaque burden, smaller lumen areas, with
      greater necrotic core and calcium content. Diabetes and Met Syn patients with
      future MACE had greater necrotic core and calcification compared with the normal
      cardiometabolic group. CONCLUSIONS: In this PCI ACS population, patients with
      diabetes and Met Syn had higher 3-year MACE rates. Lesion length, plaque burden,
      necrotic core, and calcium content were significantly greater among nonculprit
      lesions of patients with diabetes and Met Syn, but only necrotic core and calcium
      were significantly greater in the nonculprit lesions of patients with a future
      MACE in this exploratory analysis.

PMID- 22421231
TI  - Coronary plaque composition, morphology, and outcomes in patients with and
      without chronic kidney disease presenting with acute coronary syndromes.
AB  - OBJECTIVES: This study sought to evaluate the impact of chronic kidney disease
      (CKD) on coronary atherosclerotic plaque composition, morphology, and outcomes in
      patients with acute coronary syndromes (ACS). BACKGROUND: CKD patients presenting
      with ACS are at increased risk for adverse events. Whether or not this increased
      risk reflects differences in coronary plaque composition remains unknown.
      METHODS: In the PROSPECT (Providing Regional Observations to Study Predictors of
      Events in the Coronary Tree) study, patients presenting with ACS in whom
      percutaneous coronary intervention was successful underwent 3-vessel grayscale
      and radiofrequency intravascular ultrasound imaging. Lesions were prospectively
      characterized, and patients were followed for a median of 3.4 years. We conducted
      a patient-level and lesion-level analysis of study participants by comparing
      intravascular ultrasound parameters of untreated nonculprit lesions in patients
      with and without CKD. RESULTS: Patients with CKD (n = 73, 11.3%) were older, more
      often female and diabetic compared to those without CKD (n = 573). Nonculprit
      lesions in patients with (n = 280) versus without (n = 2,390) CKD were more
      likely to have plaque burden >= 70% (11.8% vs. 8.5%, p = 0.05) and minimal
      luminal area <= 4.0 mm(2) (25.9% vs. 19.2%, p = 0.005). The percentage of plaque
      comprised of necrotic core (15.0% vs. 13.0%, p = 0.0001) and dense calcium (8.2%
      vs. 6.4%, p < 0.0001) was higher while fibrous tissue (57.7% vs. 59.8%, p <
      0.0001) was lower in CKD versus non-CKD lesions. The 3-year composite rate of
      cardiac death, cardiac arrest, or myocardial infarction (15.1% vs. 3.3%, p <
      0.0001) was significantly higher in patients with than in those without CKD,
      although there were no differences in the rates of events adjudicated to
      nonculprit lesions. CONCLUSIONS: Following percutaneous coronary intervention of
      all culprit lesions in ACS, patients with versus without CKD have more extensive
      and severe atherosclerosis remaining in their coronary tree with plaque composed
      of greater necrotic core and less fibrous tissue. These influences resulted in
      nonsignificantly different rates of non-culprit lesion-related adverse events,
      although cardiac death, arrest, or myocardial infarction were more common in
      patients with CKD.

PMID- 22421232
TI  - Gender and the extent of coronary atherosclerosis, plaque composition, and
      clinical outcomes in acute coronary syndromes.
AB  - OBJECTIVES: This study sought to assess the extent and composition of
      atherosclerosis contributing to acute coronary syndrome events in women compared
      with men. BACKGROUND: Pathological studies suggest that plaque composition and
      burden may differ by sex. It is unclear whether sex impacts the extent,
      characteristics, and potential vulnerability of coronary plaques. METHODS: A
      total of 697 patients (24% women) with acute coronary syndromes were enrolled in
      the prospective, multicenter PROSPECT (Providing Regional Observations to Study
      Predictors of Events in the Coronary Tree) study. Three-vessel multimodality
      intracoronary imaging (quantitative coronary angiography, grayscale, and
      radiofrequency intravascular ultrasound [IVUS]) was performed after treatment of
      the culprit lesion(s). Events during a median 3.4-year follow-up were ascribed to
      recurrent culprit versus untreated nonculprit lesions. The authors performed a
      post hoc, sex-based subgroup analysis. RESULTS: Women were older and had more
      comorbid disease than men. By angiography, women had a similar number of
      angiographic culprit (p = 0.53) but fewer nonculprit (p = 0.05) lesions, and
      fewer vessels with nonculprit lesions (p = 0.048) compared with men even after
      multivariable adjustment (p = 0.002). By IVUS, women had fewer nonculprit lesions
      (p = 0.002), but similar plaque burden (PB) per lesion (55.6% vs. 55.3%; p =
      0.35), and female sex was not predictive of severe (> 70%) PB (p = 0.052). Plaque
      rupture was less common in women (6.6% vs. 16.3%; p = 0.002) even after adjusting
      for comorbidities (p = 0.004), as was the total necrotic core volume (p <
      0.0001). The frequency of other plaque phenotypes was similar for men and women
      including pathological intimal thickening, thin-cap fibroatheromas (TCFA), and
      thick-cap fibroatheromas. Rates of major adverse cardiovascular events attributed
      to culprit and nonculprit lesions at 1-, 2-, and 3-year follow-up were not
      significantly different between men and women, although women were rehospitalized
      more frequently due to culprit lesion-related angina. For men, nonculprit lesion
      minimal lumen area <= 4.0 mm(2), PB >=70%, and TCFA predicted nonculprit MACE at
      3 years, whereas for women, only TCFA and PB were predictive. CONCLUSIONS: The
      PROSPECT study validates that despite having more comorbid risk factors than men,
      women have less extensive coronary artery disease by both angiographic and IVUS
      measures, and that lesions in women compared with men have less plaque rupture,
      less necrotic core and calcium, similar plaque burden, and smaller lumens. TCFA
      may also be a stronger marker of plaque vulnerability in women than men.

PMID- 22421233
TI  - The PROSPECT of changing our approach to acute coronary syndromes.

PMID- 22421234
TI  - Residual plaque burden in patients with acute coronary syndromes after successful
      percutaneous coronary intervention.
AB  - OBJECTIVES: The aim of this study was to characterize and evaluate the clinical
      impact of untreated atherosclerotic disease after percutaneous coronary
      intervention (PCI) in patients with acute coronary syndromes (ACS). BACKGROUND:
      Residual atherosclerotic disease after successful PCI may predispose future major
      adverse cardiovascular events (MACE). Compared with intravascular ultrasound
      (IVUS), angiography underestimates the presence and severity of coronary artery
      disease. METHODS: Following successful PCI of all clinically significant lesions
      in 697 patients with ACS, 3-vessel grayscale and radiofrequency IVUS was
      performed. Lesions were prospectively characterized, and patients were followed
      for a median of 3.4 years. A total of 3,229 untreated lesions (4.89 +/- 1.98
      lesions/patient) were identified by IVUS, with mean plaque burden (PB) of 49.6 +/
      4.2%. RESULTS: By angiography these nonculprit lesions were mild, with mean
      diameter stenosis of 38.9 +/- 15.3%. At least 1 lesion with a PB >=70% (PB70
      lesion) was found in 220 (33%) patients. By multivariable analysis, a history of
      prior PCI and angiographic 3-vessel disease were independent predictors of PB70
      lesions. Patients with PB70 lesions had greater total percent plaque volume,
      normalized PB, fibroatheromas, thin-cap fibroatheromas, and normalized volumes of
      necrotic core and dense calcium. Patients with PB70 lesions had greater 3-year
      rates of MACE due to untreated nonculprit lesions (20.8% vs. 7.7%, p < 0.0001).
      Among imaged nonculprit lesions, the proportion of PB70 lesions causing MACE was
      significantly greater than non-PB70 lesions (8.7% vs. 1.0%, p < 0.0001).
      CONCLUSIONS: After successful PCI of all angiographically significant lesions,
      overall untreated atherosclerotic burden remains high, and PB70 lesions are
      frequently present in the proximal and mid-coronary tree. Patients with PB70
      lesions have greater atherosclerosis throughout the coronary tree, have more thin
      cap fibroatheromas, and are at increased risk for future cardiovascular events. (
      PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions;
      NCT00180466).

PMID- 22421235
TI  - Characteristics and clinical significance of angiographically mild lesions in
      acute coronary syndromes.
AB  - OBJECTIVES: The aim of this study was to assess whether residual nonculprit (NC)
      lesions, defined as visual diameter stenosis >= 30% after successful percutaneous
      coronary intervention, affect the rate of future events in patients with acute
      coronary syndromes. BACKGROUND: In patients with acute coronary syndromes,
      approximately one-half of recurrent events after percutaneous coronary
      intervention arise from untreated lesions. METHODS: Patients enrolled in PROSPECT
      (Providing Regional Observations to Study Predictors of Events in the Coronary
      Tree) were divided into 3 groups: those with no NC lesions, 1 NC lesion, or >= 2
      NC lesions. Time to events for major adverse cardiac events was estimated up to 3
      years. RESULTS: Among 697 patients, 13.3% had no NC lesions, 19.7% had 1 NC
      lesion, and 67.0% had >= 2 NC lesions. The median diameter stenoses of the NC
      lesions in the latter 2 groups were 36.7% (interquartile range: 31.0% to 43.4%)
      and 37.4% (interquartile range: 32.0% to 46.5%), respectively (p = 0.22). At
      least 1 thin-cap fibroatheroma was present in one-half the patients in each
      group. At 3 years, the incidence of major adverse cardiac events was 8.5%, 15.2%,
      and 24.3%, respectively (p = 0.0009). NC lesion-related events occurred in 0%,
      5.0%, and 15.9% of patients, respectively (p < 0.0001). Of 105 NC lesion-related
      clinical events occurring during follow-up, 73 (69.5%) originated from
      angiographically evident baseline NC lesions (of which 36 had diameter stenosis
      >50%), while the other 32 arose from normal or near normal segments. CONCLUSIONS:
      Residual NC lesions are common after percutaneous coronary intervention for acute
      coronary syndromes and portend a higher rate of recurrent ischemic events within
      3 years, especially when angiographically more severe. Conversely, the absence of
      NC lesions by angiography is highly predictive of freedom from events not related
      to the originally treated culprit lesion(s).

PMID- 22421236
TI  - Adverse cardiovascular events arising from atherosclerotic lesions with and
      without angiographic disease progression.
AB  - OBJECTIVES: The aim of this study was to use angiography and grayscale and
      intravascular ultrasound-virtual histology to assess coronary lesions that caused
      events during a median follow-up period of 3.4 years. BACKGROUND: Vulnerable
      plaque-related events are assumed to be the result of substantial progression of
      insignificant lesions. METHODS: In the PROSPECT (Providing Regional Observations
      to Study Predictors of Events in the Coronary Tree) study, 697 patients with
      acute coronary syndromes underwent treatment of all culprit lesions followed by 3
      vessel imaging to assess the natural history of culprit and untreated nonculprit
      (NC) lesions. Future adverse cardiovascular events adjudicated to NC lesions were
      divided into those with versus without substantial lesion progression (SLP) (>=
      20% angiographic diameter stenosis increase). RESULTS: NC lesion events occurred
      in 72 patients, 44 (61%) with and 28 (39%) without SLP. Myocardial infarctions (n
      = 6) occurred only in patients with SLP. Conversely, patients without SLP
      presented only with unstable or increasing angina requiring rehospitalization.
      Lesions with versus without SLP occurred later (median time to event 401 vs. 223
      days, p = 0.07); were less severe at baseline (median diameter stenosis 26.4% vs.
      53.8%, p < 0.0001) but more severe at the time of the event (mean diameter
      stenosis 73.8% vs. 56%, p < 0.0001); and had comparable baseline median plaque
      burden (68.7% vs. 70.1%, p = 0.17), minimum luminal area (3.7 vs. 4.0 mm(2), p =
      0.60), and intravascular ultrasound-virtual histology phenotype (83.3% vs. 90.9%,
      p = 0.68; classified as fibroatheromas at baseline). CONCLUSIONS: NC lesions
      responsible for future cardiovascular events showed angiographic increase during
      3.4 years of follow-up, whereas SLP underlay many but not all of them. NC events
      due to lesions with SLP were angiographically less severe and presented with a
      delayed time course but were otherwise indistinguishable from NC events that were
      not associated with SLP.

PMID- 22421237
TI  - CTO Club: revisiting the final frontier in PCI.

PMID- 22421238
TI  - Growth kinetics and size-dependent wetting of Ag/alpha-Al2O3(0001) nanoparticles
      studied via the plasmonic response.
AB  - The growth of vapour-deposited silver nanoparticles on alpha-Al2O3 was studied in
      situ from 190 to 675 K by surface differential reflectivity spectroscopy in the
      UV-visible range. Changes in size, shape and density were derived from the
      plasmonic response modelled in the framework of interface susceptibilities by
      assuming that supported clusters were in the form of truncated spheres. The
      sticking coefficient of silver on alumina is close to one up to T ? 575 K before
      entering a regime of incomplete condensation. The Arrhenius dependence of the
      saturation density indicates a nucleation on defects at low temperature (T <= 300
      K) and detrapping above. The particle size D evolution follows temporal power
      laws, independent of temperature and flux, which characterize the growth (D ~
      t(0.31)) and coalescence (D ~ t(0.55)) of the film. These are indicative of the
      growth of isolated particles at constant density and dynamic coalescence,
      respectively. The wetting angle of the silver clusters is shown to increase
      during the growth regime, which is assigned to a combination of surface stress
      and mismatch-induced strain, and to decrease upon coalescence, which is
      attributed to plastic relaxation. For particles larger than 10 nm in size, the
      values of contact angle and adhesion energy level off with asymptotic limits
      (theta(c) = 127.5 degrees  +/- 1 degrees  and 0.48 +/- 0.02 J m-2) that nicely
      agree with tabulated data. This work highlights the ability of nanoplasmics to
      monitor in situ the growth kinetics of thin supported films.

PMID- 22421239
TI  - Corpus callosum volumes in recent-onset schizophrenia are correlated to positive
      symptom severity after 1 year of follow-up.

PMID- 22421241
TI  - The signaling and functions of heterodimeric bone morphogenetic proteins.
AB  - Heterodimeric bone morphogenetic proteins (BMPs) consist of disulfide-linked
      dimeric monomers derived from different BMP members. Owing to this specific
      constitution pattern, they bear high affinity to both type I and type II BMP
      receptors simultaneously. Meanwhile, the antagonism efficiency of extracellular
      antagonists to heterodimeric BMPs is also significantly lower than that to
      homodimeric ones. All these specific properties confer heterodimeric BMPs with
      distinct signaling and bio-functions that are characterized by more speediness,
      lower concentration/dose threshold and higher efficiency than homodimeric BMPs.
      Consequently, heterodimeric BMPs bear promising application potential in inducing
      osteogenesis. In addition, they may play indispensible roles in organogenesis. In
      this review, we summarize the current knowledge of heterodimeric BMPs in their
      signaling pathways and bio-functions.

PMID- 22421242
TI  - Second stem cell transplants for multiple myeloma. If at once you don't succeed,
      should we really try, try again?

PMID- 22421240
TI  - Starting at the beginning: the neuropsychological status of children with new
      onset epilepsies.
AB  - This review examines the neurodevelopmental contribution to the cognitive and
      behavioural complications of epilepsy. Following a brief review of the lifespan
      complications of childhood epilepsies, attention turns to cognitive, psychiatric
      and social correlates of childhood epilepsies reported in population-based and
      tertiary care studies. The focus then becomes the neurobehavioural status of
      children with new-onset epilepsy; a point in time not confounded by the effects
      of years of recurrent seizures, medications, and social reactions to epilepsy.
      Recent research shows that abnormalities in cognition, brain structure and
      behaviour are present at or near the time of diagnosis. Further, careful history
      taking indicates that neurobehavioural problems may be present in advance of the
      first seizure suggesting the potential influence of epileptogenesis, antecedent
      neurodevelopmental abnormalities, genetic and environmental susceptibilities, and
      other risk factors. This becomes the substrate upon which to characterise the
      effects of epilepsy and its treatment on subsequent neurodevelopment. The review
      concludes with suggestions for future clinical care and research.

PMID- 22421243
TI  - Viral load monitoring of antiretroviral therapy, cohort viral load and HIV
      transmission in Southern Africa:  a mathematical modelling analysis.
AB  - OBJECTIVES: In low-income settings, treatment failure is often identified using
      CD4 cell count monitoring. Consequently, patients remain on a failing regimen,
      resulting in a higher risk of transmission. We investigated the benefit of
      routine viral load monitoring for reducing HIV transmission. DESIGN: Mathematical
      model. METHODS: We developed a stochastic mathematical model representing the
      course of individual viral load, immunological response and survival in a cohort
      of 1000 HIV-infected patients receiving antiretroviral therapy (ART) in southern
      Africa. We calculated cohort viral load (CVL; sum of individual viral loads) and
      used a mathematical relationship between individual viral load values and
      transmission probability to estimate the number of new HIV infections. Our model
      was parameterized with data from the International epidemiologic Databases to
      Evaluate AIDS Southern African collaboration. Sensitivity analyses were performed
      to assess the validity of the results in a universal 'test and treat' scenario,
      wherein patients start ART earlier after HIV infection. RESULTS: If CD4 cell
      count alone was regularly monitored, the CVL was 2.6 * 10 copies/ml and the
      treated patients transmitted on average 6.3 infections each year. With routine
      viral load monitoring, both CVL and transmissions were reduced by 31% to 1.7 * 10
      copies/ml and 4.3 transmissions, respectively. The relative reduction of 31%
      between monitoring strategies remained similar for different scenarios.
      CONCLUSION: Although routine viral load monitoring enhances the preventive effect
      of ART, the provision of ART to everyone in need should remain the highest
      priority.

PMID- 22421244
TI  - Adjunctive interferon-gamma immunotherapy for the treatment of HIV-associated
      cryptococcal meningitis:  a randomized controlled trial.
AB  - BACKGROUND: Interferon-gamma (IFNgamma) is of key importance in the immune
      response to Cryptococcus neoformans. Mortality related to cryptococcal meningitis
      remains high, and novel treatment strategies are needed. We performed a
      randomized controlled trial to determine whether addition of IFNgamma to standard
      therapy increased the rate of clearance of cryptococcal infection in HIV
      associated cryptococcal meningitis. METHODS: Patients were randomized to
      amphotericin B 1 mg/kg per day and 5FC 100 mg/kg per day for 2 weeks (standard
      therapy), standard therapy and IFNgamma1b 100 MUg days 1 and 3 (IFNgamma two
      doses), or standard therapy and IFNgamma1b 100 MUg days 1, 3, 5, 8, 10 and 12
      (IFNgamma six doses). Primary outcome was rate of clearance of cryptococcus from
      the cerebrospinal fluid (CSF) (early fungicidal activity, EFA) calculated from
      serial quantitative cultures, previously shown to be independently associated
      with survival. RESULTS: Rate of fungal clearance was significantly faster in
      IFNgamma containing groups than with standard treatment. Mean EFA [log colony
      forming unit (CFU)/ml per day] was -0.49 with standard treatment, -0.64 with
      IFNgamma two doses, and -0.64 with IFNgamma six doses. Difference in EFA was 
      0.15 [confidence interval (95% CI) -0.02 to -0.27, P=0.02] between standard
      treatment and IFNgamma two doses, and -0.15 (95% CI -0.05 to -0.26, P=0.006)
      between standard treatment and IFNgamma six doses. Mortality was 16% (14/88) at 2
      weeks and 31% (27/87) at 10 weeks, with no significant difference between groups.
      All treatments were well tolerated. CONCLUSION: Addition of short-course IFNgamma
      to standard treatment significantly increased the rate of clearance of
      cryptococcal infection from the CSF, and was not associated with any increase in
      adverse events. Two doses of IFNgamma are as effective as six doses.

PMID- 22421245
TI  - A time lag insensitive approach for estimating HIV-1 transmission direction.
AB  - OBJECTIVES: Identifying the direction of transmission in transmission pairs is
      important both for forensic investigations and for the monitoring of HIV
      epidemics, however, reliable methods are not yet available due to the long time
      lag between infection and sampling in most real cases. DESIGNS: Based on
      bottleneck effect and coreceptor switching, we aimed at identifying an estimator
      from sequences of viral gp120 proteins to determine transmission direction
      between transmission pairs. The estimator should be changed with HIV transmission
      but was independent of disease progression in an individual. METHODS: Here, we
      present a novel and reliable approach for identifying transmission direction. We
      derived a set of conserved patterns, called common patterns, from the sequences
      of viruses, which differed in their coreceptor usage. The number of unique common
      patterns in viral sequences decreased with transmission but remained almost
      constant with the progress of disease in an individual. We used this number as an
      estimator to determine transmission direction in 73 transmission pairs for which
      the transmission direction was already known. RESULTS: Our method predicted
      transmission direction with an accuracy of up to 94.5%. Of greater importance,
      our approach was not influenced by time lags between infection and sampling, and
      even transmission direction for transmission pairs with long time lags ranging
      from 2 years to more than 18 years were correctly determined. CONCLUSION: Our
      approach for accurately determining transmission direction between transmission
      pairs is irrespective of the time lag between infection and sampling, which means
      a promising applications prospect.

PMID- 22421246
TI  - Comparison of carpal tunnel release with three different techniques.
AB  - BACKGROUND: Carpal tunnel syndrome is one of the most common compression
      neuropathies in the upper limbs and requires surgery if conservative treatment
      fails. This article compares the result of regular open incision, mid-palmar mini
      incision and endoscopic technique in carpal tunnel release. METHODS: This is a
      clinical trial study on 105 patients (10 males, 95 females) within one year, who
      were surgical candidates. The surgery was done with regular open incision or with
      mid-palmar small incision. The clinical outcomes were evaluated one week, 4 weeks
      and 4 months post-surgery. RESULTS: Relief and satisfaction were better in the
      first month in the endoscopic and mid-palmar mini incision group. All 3
      techniques had similar outcomes after 4 months. In the 4-month follow-up, night
      pain relief, followed by parasthesia relief had the best improvement. Weakness
      was the symptom with the least improvement. Longer incision cases were associated
      with more delay to return to work. CONCLUSION: Carpal tunnel release with
      endoscopic and mini incision techniques have better early satisfaction rates
      compared to regular open incision, but no difference is seen between the two
      groups after four months.

PMID- 22421247
TI  - The clinical practice of reconstructive neurosurgery.
AB  - Surgical interventions to improve function following nervous system injury have
      been in development since the early 1900s. Only recently these have been
      assimilated into a coherent approach which can be applied to injuries of the
      brain, spinal cord and peripheral nerves. In addition to pharmacological and
      stimulation based interventions, surgical manipulation of the peripheral nerves
      and muscles of the extremity can offer functional enhancement for a variety of
      limb impairments. In order to plan an effective surgical intervention,
      neurophysiological assessment of the injury and residual motor control is
      essential. Effective implementation of these surgical interventions can enhance
      function and quality of life for many individuals whose activity has been limited
      as a result of nervous system injury.

PMID- 22421248
TI  - Microsurgery for cerebral cysticercosis.

PMID- 22421249
TI  - Melanocytic tumor with GNA11 p.Q209L mutation mimicking a foramen magnum
      meningioma.

PMID- 22421250
TI  - Pharmacokinetic considerations in the repositioning of mefloquine for treatment
      of progressive multifocal leukoencephalopathy.

PMID- 22421251
TI  - Two cases of posterior reversible encephalopathy syndrome resembling brainstem
      glioma.

PMID- 22421252
TI  - Intrathecal large granular lymphocytes as an unusual presentation of a small cell
      T cell lymphoma.

PMID- 22421253
TI  - MuSK myasthenia gravis and Lambert-Eaton myasthenic syndrome in the same patient.

PMID- 22421254
TI  - Intracranial intradural chordoma presenting with intraventricular hemorrhage.

PMID- 22421255
TI  - Radiation induced intraparenchymal meningioma occurring 6 years after CNS
      germinoma: case report.

PMID- 22421256
TI  - Prenatal exposures to environmental chemicals and birth order as risk factors for
      child behavior problems.
AB  - OBJECTIVES: To assess whether polychlorinated biphenyls (PCBs), methylmercury,
      lead, or parental child-rearing attitudes was most crucial for maladaptive
      behavior problems, we examined Japanese 30-month-old children followed up from
      pregnancy. METHODS: The Child Behavior Checklist (CBCL) was used to assess the
      behavior problems in 306 children. The associations of cord-blood total PCBs
      (SigmaPCB), total mercury (THg), and lead with each CBCL subscale were examined
      by multivariate analyses. RESULTS: The median values in cord blood of the 306
      children were 48.3 (5 and 95 percentiles, 18.6-116.3) ng/g-lipid for SigmaPCB,
      10.2 (4.1-24.5)ng/g for THg, and 1.0 (0.5-1.7)MUg/dl for lead. The internalizing
      score of the CBCL was significantly correlated with SigmaPCB (r=0.113) in the
      children, though no significant correlation was seen between any CBCL score and
      either THg or lead. The significant correlation disappeared when conducting
      multiple regression analysis with possible confounders; at that time, the birth
      order, home environment, and maternal intelligence quotient were significantly
      related to the internalizing score. Three CBCL scores and SigmaPCB levels were
      significantly higher in the first-born children than in the second-born or
      following children, and the partial correlation coefficient with the adjustment
      for all confounders except birth order was significant between the internalizing
      score and SigmaPCB in the latter children (r=0.175). CONCLUSIONS: Internalizing
      behavior appears to be affected by prenatal exposure to PCBs at low levels. Under
      lower-level exposures, however, behavior problems may be more strongly associated
      with parental child-rearing attitudes involved in birth order, than with such
      hazardous chemicals.

PMID- 22421257
TI  - The value of the intra-operative clinical mechanical axis measurement in open
      wedge valgus high tibial osteotomies.
AB  - INTRODUCTION: In high tibial osteotomies (HTO) the correction needs to be precise
      and intra-operative assessment is essential. The purpose of this study was to
      evaluate the use of the intra-operative clinical mechanical axis measurement and
      compare it to the post-operative weight bearing situation on standing whole leg
      radiographs (WLR). Secondly, we evaluated the preoperative planned wedge size and
      compared it to the final results in 27 HTOs. METHODS: The mechanical axis
      deviation (MAD), expressed as a percentage of the tibial width (0% is medial
      edge, 100% is lateral edge) and the hip-knee-ankle angle (HKA) were calculated
      and analyzed. Preoperative planning was done by projecting the desired mechanical
      axis on the lateral tibial spine on the WLR and subsequently calculating the
      necessary correction angle. A 3 degrees  valgus correction was desired. RESULTS:
      The results showed a preoperative standing MAD of 26.6%, or about halfway the
      medial tibial plateau. The MAD was corrected to 57.0% intra-operative, meaning a
      slight valgus. On the postoperative standing WLR, the MAD had shifted
      significantly to 62.0% (95% CI=-9.2 to -2.7; p<0.01) compared to the intra
      operative 57.0% axis. The HKA angle changed 8.2 degrees  from 5.1 degrees  varus
      preoperative to 3.1 degrees  valgus postoperative. CONCLUSION: When aiming the
      mechanical axis at the lateral tibial spine, a slight undercorrection was
      introduced, but due to a valgus shift while weight bearing, a satisfying final
      outcome of 3 degrees  valgus average was achieved. Preoperative calculation of
      the wedge size remains important for surgical planning, but it does not always
      correspond to the actual used wedge size.

PMID- 22421258
TI  - Infections caused by multidrug resistant organisms are not associated with
      overall, all-cause mortality in the surgical intensive care unit: the 20,000 foot
      view.
AB  - BACKGROUND: Resistant pathogens are increasingly common in the ICU, with
      controversy regarding their relationship to outcomes. We hypothesized that an
      increasing number of infections with resistant pathogens in our surgical ICU
      would not be associated with increased overall mortality. STUDY DESIGN: All ICU
      acquired infections were prospectively identified between January 1, 2000 and
      December 31, 2009 in a single surgical ICU. Crude in-hospital, all-cause
      mortality data were obtained using a prospectively collected ICU database. Trends
      in rates were compared using linear regression. RESULTS: A total of 799 resistant
      pathogens were identified (257 gram-positive, 542 gram-negative) from a total of
      3,024 isolated pathogens associated with 2,439 ICU-acquired infections. The most
      frequently identified resistant gram-positive and -negative pathogens (defined as
      resistant to at least 1 major class of antimicrobials) were methicillin-resistant
      Staphylococcus aureus and Pseudomonas aeruginosa, respectively. Pathogens were
      most commonly isolated from the lung, blood, and urine. The crude mortality rate
      declined steadily from 2000 to 2009 (9.4% to 5.4%; equation for trend y = -0.11x
      + 8.26). Linear regression analysis of quarterly rates revealed a significant
      divergence in trends between increasing total resistant infections (equation for
      trend y = 0.34x + 13.02) and percentage resistant infections (equation for trend
      y = 0.36x + 18.66) when compared with a decreasing mortality (p = 0.0003, p <
      0.0001, respectively). CONCLUSIONS: Despite a steady rise in the proportion of
      resistant bacterial infections in the ICU, crude mortality rates have decreased
      over time. The rates of resistant infections do not appear to be a significant
      factor in overall mortality in our surgical ICU patients.

PMID- 22421259
TI  - Thoracolaparoscopic esophagectomy: is the prone position a safe alternative to
      the decubitus position?
AB  - BACKGROUND: During the last few years, prone thoracoscopic esophagectomy has been
      increasingly adopted for thoracolaparoscopic esophagectomy (TLE). However,
      evidence for the prone position (PP) over the decubitus position (DP) during TLE
      is currently not strong enough to reach conclusions. STUDY DESIGN: From May 2009
      to December 2010, we conducted thoracoscopic esophagectomies in the DP and then
      PP on consecutive patients admitted to our institution. TLE in DP was conducted
      from May 2009 to February 2010 and in PP from March 2010 to December 2010.
      Clinical features and operation characteristics of all patients were collected
      and compared to determine differences between the 2 groups. RESULTS: A total of
      93 consecutive esophageal cancer patients were enrolled; Forty-one had their
      operations in DP and 52 in PP. There was no significant difference found between
      the 2 groups in age, sex, body mass index, tumor location, histological type, and
      TNM stage. When compared with DP, thoracoscopic esophagectomy in PP had a shorter
      operation duration (67 vs 77 minutes; p = 0.013), horter overall hospital stay
      (17.4 vs 11.4 days; p = 0.011), and yielded a larger number of lymph nodes (11.6
      +/- 4.0 vs 8.9 +/- 4.9 on average; p = 0.005). Complication rates were similar
      between the 2 groups, with anastomotic leak developing in a significantly smaller
      number of patients in PP (7.7% vs 22.0%; p = 0.049). CONCLUSIONS: TLE in the PP
      is a feasible and safe alternative to DP and is potentially associated with fewer
      complications. Additional randomized studies are required to discuss the long
      term prognostic value of this procedure.

PMID- 22421260
TI  - What are the real rates of postoperative complications: elucidating
      inconsistencies between administrative and clinical data sources.
AB  - BACKGROUND: Comparison of quality outcomes generated from administrative and
      clinical datasets have shown inconsistencies. Understanding this is important
      because data designed to drive performance improvement are used for public
      reporting of performance. We examined administrative and clinical data and 2
      clinical data sources in 4 surgical morbidity outcomes. STUDY DESIGN: Patients
      who underwent operations between January 2009 and May 2010 had outcomes compared
      for postoperative hemorrhage, respiratory failure, deep vein thrombosis (DVT),
      and sepsis. Three data sources were examined: administrative (Agency for
      Healthcare Research and Quality [AHRQ] Patient Safety Indicators [PSIs]), a
      national clinical registry (National Surgical Quality Improvement Program
      [NSQIP]), and an institutional clinical registry (Cardiovascular Information
      Registry [CVIR]). Cohen's Kappa (K) coefficient was used as a measure of
      agreement between data sources. RESULTS: For 4,583 patients common to AHRQ and
      NSQIP, concordance was poor for sepsis (K = 0.07) and hemorrhage (K = 0.14),
      moderate for respiratory failure (K = 0.30), and better concordance for DVT (K =
      0.60). For 7,897 patients common to AHRQ and CVIR, concordance was poor for
      hemorrhage (K = 0.08), respiratory failure (K = 0.02), and sepsis (K = 0.16), and
      better for DVT (K = 0.55). For 886 patients common to NSQIP and CVIR, concordance
      was poor for sepsis (K = 0.054), moderate for hemorrhage (K = 0.27) and
      respiratory failure (K = 0.4), and better for DVT (K = 0.51). CONCLUSIONS: We
      demonstrate considerable discordance between data sources measuring the same
      postoperative events. The main contributor was difference in definitions, with
      additional contribution from data collection and management methods. Although any
      of these sources can be used for their original intent of performance
      improvement, this study emphasizes the shortcomings of using these sources for
      grading performance without standardizing definitions, data collection, and
      management.

PMID- 22421262
TI  - Quality of life and behavioral functioning in Dutch children with a history of
      Kawasaki disease.
AB  - OBJECTIVE: The authors evaluated health-related quality of life (HRQOL) and
      behavioral functioning in patients with a history of Kawasaki disease (KD). STUDY
      DESIGN: A cross-sectional study was conducted at a tertiary referral center for
      KD follow-up in 280 patients (mean age 8.6 years, 60.0% male). Patients were
      eligible when they were aged 0-18 years and had a history of KD. HRQOL was
      assessed using the TNO-AZL Preschool Children Quality of Life questionnaire for
      children 0-5 years old and the Pediatric Inventory of Quality of Life Core Scales
      4.0 for those 6-18 years old. Behavioral functioning was evaluated using the
      Strength and Difficulties Questionnaire (8-16 years proxy report and 11-16 years
      self-report). KD results were compared with Dutch norm data, and patients with
      and without coronary artery aneurysms were compared. RESULTS: HRQOL was
      significantly worse for male patients aged 0-5 years on 4 of the 12 TNO-AZL
      Preschool Children Quality of Life questionnaire scales and for female patients
      on the motor functioning scale. At an older age, the HRQOL of patients was
      comparable with the norm population. Coronary artery status did not influence
      HRQOL. Parents reported more behavioral problems on the hyperactivity and
      emotional subscale in patients compared with the norm population. CONCLUSIONS:
      Although at an older age the HRQOL of patients with KD is comparable with the
      Dutch norm, HRQOL seems to be particularly impaired at younger age. Parents
      reported more hyperactivity and emotional problems in patients with KD.

PMID- 22421263
TI  - Early term delivery and health care utilization in the first year of life.
AB  - OBJECTIVE: To assess health care utilization during the first year of life among
      early term-born infants. STUDY DESIGN: We assessed health care utilization of
      22420 singleton term infants (37-42 weeks gestational age [GA]) without major
      birth defects, fetal growth restriction, or exposure to diabetes or hypertension
      in utero, delivered between 1998 and 2007 and continuously enrolled at Kaiser
      Permanente Northwest for 12 months after delivery. GA, duration of delivery
      hospitalization, and postdelivery rehospitalizations and sick/emergency room
      visits in the first year of life were obtained from electronic medical records.
      Logistic regression models were used to estimate associations between GA and
      number of hospitalizations and length of stay. Generalized linear models were
      used to estimate the adjusted mean number of sick/emergency visits. RESULTS:
      Overall, 20.9% of term infants were born early. Infants delivered vaginally at 37
      weeks GA had a 2.2 greater odds (95% CI, 1.6-3.1) of staying 4 or more days
      compared with those born at 39-40 weeks GA. Similar association was found among
      infants delivered by cesarean delivery at 37 or 38 weeks GA. Infants born at 37
      weeks GA had increased odds of being rehospitalized within 2 weeks of delivery
      (OR, 2.6; 95% CI, 1.9-3.6). The adjusted mean number of sick/emergency room
      visits was higher for infants born at 37 and 38 weeks GA than for those born at
      39-40 weeks GA (8.1, 7.7, and 7.3, respectively; P < .0001). CONCLUSIONS: Early
      term-born infants had greater health care utilization during their entire first
      year of life than infants born at 39-40 weeks GA.

PMID- 22421265
TI  - Double positivity to bee and wasp venom: improved diagnostic procedure by
      recombinant allergen-based IgE testing and basophil activation test including
      data about cross-reactive carbohydrate determinants.
AB  - BACKGROUND: Specific IgE (sIgE) antibodies to both bee and wasp venom can be due
      to a sensitivity to both insect venoms or due to cross-reactive carbohydrate
      determinants (CCDs). OBJECTIVE: Investigating whether a basophil activation test
      (BAT) with both venoms as well as with bromelain and horseradish peroxidase (HRP)
      or recombinant allergen-based IgE testing can improve the diagnostic procedure.
      METHODS: Twenty-two Hymenoptera-venom allergic patients with sIgE antibodies to
      both bee and wasp venom were studied. sIgE antibodies to MUXF3 CCD, bromelain,
      HRP, rApi m 1, and rVes v 5 were determined, and a BAT (Flow2 CAST) with venom
      extracts, bromelain, and HRP was performed. Further recombinant allergen-based
      IgE testing was done by using an ELISA, if required. The reactivity of basophils
      was calculated from the insect venom concentration at half-maximum stimulation.
      RESULTS: Double positivity/double negativity/single positivity to rApi m 1 and
      rVes v 5 was seen in 12/1/9 patients. Further recombinant allergen-based IgE
      testing in the last ones revealed positive results to the other venom in all
      cases except one. BAT was double positive/double negative/single positive in
      6/2/14 patients. Four patients with negative results in sIgE antibodies to CCDs
      had positive results in BAT. BAT with bromelain/HRP showed a sensitivity of
      50%/81% and a specificity of 91%/90%. CONCLUSION: Component-resolved IgE testing
      elucidates the pattern of double positivity, showing a majority of true double
      sensitizations independent of CCD sensitization. BAT seems to add more
      information about the culprit insect even if the true clinical relevance of BAT
      is not completely determined because of ethical limitations on diagnostic sting
      challenges. BAT with HRP is a good method to determine sensitivity to CCDs.

PMID- 22421266
TI  - Effect of precautionary statements on the purchasing practices of Canadians
      directly and indirectly affected by food allergies.

PMID- 22421264
TI  - Correlates of resistin in children with chronic kidney disease: the chronic
      kidney disease in children cohort.
AB  - OBJECTIVE: To test the hypothesis that resistin is associated with insulin
      resistance and inflammation in pediatric patients with chronic kidney disease
      (CKD). STUDY DESIGN: This study is a cross-sectional analysis of 319 children in
      the Chronic Kidney Disease in Children cohort, a large cohort of children with
      stage II-IV CKD. Univariate and multivariate regression modeling was used to
      evaluate the association of serum resistin level with glomerular filtration rate
      (GFR), demographic data, and cardiovascular risk factors, including inflammatory
      cytokines, insulin resistance, and serum lipids. RESULTS: In univariate analyses,
      serum resistin level was negatively correlated with GFR (P < .01). Increased
      serum resistin was associated with elevated inflammatory cytokines, including
      interleukin (IL)-6 (P < .01), IL-10 (P < .01), and tumor necrosis factor-alpha (P
      < .01). Resistin level was not associated with insulin resistance, although it
      was positively correlated with serum triglycerides (P < .01) and negatively
      correlated with high-density lipoprotein cholesterol (P < .01). In multivariate
      analysis, GFR (beta = -0.01; P < .001), IL-6 (beta = 0.18; P < .001), IL-10 (beta
      = 0.09; P = .01), and pubertal status (beta = 0.18; P < .01) were significantly
      associated with serum resistin level. CONCLUSION: These results indicate that
      serum resistin level increases with GFR decline and is involved in the
      inflammatory milieu present in CKD.

PMID- 22421267
TI  - Epistatic interaction between Toll-like receptor 3 (TLR3) and prostaglandin E
      receptor 3 (PTGER3) genes.

PMID- 22421261
TI  - Are outcomes of extremely preterm infants improving? Impact of Bayley assessment
      on outcomes.
AB  - OBJECTIVES: To compare 18- to 22-month cognitive scores and neurodevelopmental
      impairment (NDI) in 2 time periods using the National Institute of Child Health
      and Human Development's Neonatal Research Network assessment of extremely low
      birth weight infants with the Bayley Scales of Infant Development, Second Edition
      (Bayley II) in 2006-2007 (period 1) and using the Bayley Scales of Infant and
      Toddler Development, Third Edition (Bayley III), with separate cognitive and
      language scores, in 2008-2011 (period 2). STUDY DESIGN: Scores were compared with
      bivariate analysis, and regression analyses were run to identify differences in
      NDI rates. RESULTS: Mean Bayley III cognitive scores were 11 points higher than
      mean Bayley II cognitive scores. The NDI rate was reduced by 70% (from 43% in
      period 1 to 13% in period 2; P < .0001). Multivariate analyses revealed that
      Bayley III contributed to a decreased risk of NDI by 5 definitions: cognitive
      score <70 and <85, cognitive or language score <70; cognitive or motor score <70,
      and cognitive, language, or motor score <70 (P < .001). CONCLUSION: Whether the
      Bayley III is overestimating cognitive performance or whether it is a more valid
      assessment of emerging cognitive skills than the Bayley II is uncertain. Because
      the Bayley III identifies significantly fewer children with disability, it is
      recommended that all extremely low birth weight infants be offered early
      intervention services at the time of discharge from the neonatal intensive care
      unit, and that Bayley scores be interpreted with caution.

PMID- 22421268
TI  - Direct measurement of free estradiol in human serum by equilibrium dialysis
      liquid chromatography-tandem mass spectrometry and reference intervals of free
      estradiol in women.
AB  - BACKGROUND: Measurement of free estradiol offers a better representation of the
      bioactive fraction of the hormone. We describe a direct equilibrium dialysis
      liquid chromatography-tandem mass spectrometry (ED-LC-MS/MS) method for serum
      free estradiol. METHODS: Two hundred fifty microliter aliquots of serum were
      dialyzed for 22h followed by liquid-liquid extraction and derivatization with
      dansyl chloride. Free estradiol was measured using LC-MS/MS with an AB SCIEX 5500
      mass spectrometer in positive ion and multiple reaction monitoring (MRM) mode.
      RESULTS: The limits of detection and quantification for free estradiol were 0.25
      and 0.5pg/ml (0.9 and 1.8pmol/l) respectively. Total imprecision was less than
      10%. Results of method comparison showed 3 times overestimation using indirect
      methods of measurement. Reference intervals in pre-menopausal women in
      follicular, mid-cycle, and luteal phases of cycle were <2.4, <3.1 and <2.6pg/ml
      (8.8, 11.4, 9.5pmol/l) respectively; in post menopausal women the concentrations
      were <=0.5pg/ml (1.8pmol/l). CONCLUSIONS: ED-LC-MS/MS is a direct method for
      accurately measuring free estradiol, independent of total estradiol or sex
      hormone binding globulin concentrations. Imprecision and sensitivity of the
      method are adequate for clinical diagnostic applications. The degree of variation
      observed in the method comparison reinforces the relevance of method specific
      reference ranges.

PMID- 22421269
TI  - Null-space function estimation for the interior problem.
AB  - In single-photon emission computed tomography (SPECT), projection data can be
      truncated when the camera's field of view is smaller than the object to be
      imaged. Using truncated projections to reconstruct a region of interest (ROI) is
      a reality we must face if small detectors are used. The truncated data result in
      an underdetermined system of imaging equations, which may lead to non-unique
      solutions. Data sampling and photon attenuation may also affect the solution
      uniqueness and stability. The uniqueness of the solutions in the ROI can be
      investigated by studying the null-space functions in the ROI. This paper uses an
      iterative algorithm to estimate the null-space image, to determine the sampling
      conditions under which a stable ROI reconstruction is possible with truncated
      data and to investigate whether attenuation can influence the ROI reconstruction
      bias. This iterative algorithm is validated by the singular value decomposition
      method. We show that if the ROI is sufficiently sampled, the null-space image is
      close to zero inside the ROI, and any almost-zero offset is insignificant in
      SPECT, because the noise is a much more dominating degradation factor.

PMID- 22421270
TI  - Reactive oxygen species and mitogen-activated protein kinase induce apoptotic
      death of SH-SY5Y cells in response to fipronil.
AB  - There are multiple lines of evidence showing that environmental toxicants
      including pesticides may contribute to neuronal cell death. Fipronil (FPN) is a
      phenylpyrazole insecticide that acts on insect GABA receptors. Although the
      action of FPN is restricted to insect neuronal or muscular transmitter systems, a
      few studies have assessed the effects of this neurotoxicant on neuronal cell
      death distinct from an insect. To determine the mechanisms underlying FPN-induced
      neuronal cell death, we evaluated the ability of this chemical to induce
      oxidative stress and studied the involvement of mitogen activated protein kinases
      (MAPKs) in FPN-induced apoptosis stress in human neuroblastoma SH-SY5Y (SH-SY5Y)
      cells. Exposure of SH-SY5Y cells to FPN led to the production of reactive oxygen
      species (ROS) and apoptotic cell death via activation of caspase-9 and caspase-3.
      Interestingly, the antioxidant, N-acetyl-cysteine (NAC) attenuated apoptotic cell
      death and ROS production induced by FPN. These results indicated that oxidative
      stress plays a central role in FPN-induced cytotoxicity. Mitochondrial complex I
      activity was also inhibited by FPN treatment. These finding indicate that FPN
      triggers intrinsic apoptosis via the mitochondrial signaling pathway that is
      initiated by the generation of ROS. Furthermore, FPN treatment induced
      phosphorylation of MAPK members. Activation of these protein kinases by FPN was
      involved in the onset of apoptosis as inhibitors specific to these kinases
      protect against FPN-induced cell death as well as ROS generation. Our data
      indicate that FPN-induced apoptosis is mediated primarily by the generation of
      ROS and activation of MAPK members followed by activation of the intrinsic
      apoptotic pathway.

PMID- 22421271
TI  - Conditioned medium from actinomycin D-treated apoptotic cells induces
      mitochondria-dependent apoptosis in bystander cells.
AB  - Chemical-induced bystander effects have been known for several years, but the
      underlying mechanism is still seldom investigated. Previous researchers have
      found that mitomycin C and phleomycin induced micronuclei in bystander cells the
      same as in exposed cells. We previously demonstrated the ability of actinomycin D
      (ACTD) to induce bystander effects in normal Chinese hamster fibroblast V79 cells
      and found that conditioned medium (CM) obtained from ACTD-exposed apoptotic cells
      induced apoptosis in bystander cells. The present study further explores the
      probable mechanism of apoptosis in bystander cells. The main findings of this
      study are: (1) ACTD-treated CM induced apoptosis in bystander cells in a time
      dependent manner, which was confirmed with morphological changes. (2) ACTD
      treated CM increased the mRNA and protein levels of pro-apoptotic p53 and Bax,
      whereas it decreased those of anti-apoptotic Bcl-2 in bystander cells; these were
      all time-dependent effects. Reactive oxygen species (ROS) were also involved in
      apoptosis of bystander cells. (3) ACTD-treated CM reduced mitochondria membrane
      potential and induced cytochrome c release. (4) ACTD-treated CM induced G1 cell
      phase arrest, which may be another response in bystander cells when cultured with
      CM. These results suggest that chemical-treated CM induces p53-Bcl-2/Bax
      cytochrome c signaling (i.e., mitochondria pathway)-dependent apoptosis in
      bystander cells, which is a kinetic response.

PMID- 22421272
TI  - Effect of age on toxicokinetics among human volunteers exposed to propylene
      glycol methyl ether (PGME).
AB  - Aging adults represent the fastest growing population segment in many countries.
      Physiological and metabolic changes in the aging process may alter how aging
      adults biologically respond to pollutants. In a controlled human toxicokinetic
      study (exposure chamber; 12 m3), aging volunteers (n=10; >58 years) were exposed
      to propylene glycol monomethyl ether (PGME, CAS no. 107-98-2) at 50 ppm for 6 h.
      The dose-dependent renal excretion of oxidative metabolites, conjugated and free
      PGME could potentially be altered by age. AIMS: (1) Compare PGME toxicokinetic
      profiles between aging and young volunteers (20-25 years) and gender; (2) test
      the predictive power of a compartmental toxicokinetic (TK) model developed for
      aging persons against urinary PGME concentrations found in this study. METHODS:
      Urine samples were collected before, during, and after the exposure. Urinary PGME
      was quantified by capillary GC/FID. RESULTS: Differences in urinary PGME profiles
      were not noted between genders but between age groups. Metabolic parameters had
      to be changed to fit the age adjusted TK model to the experimental results,
      implying a slower enzymatic pathway in the aging volunteers. For an appropriate
      exposure assessment, urinary total PGME should be quantified. CONCLUSION: Age is
      a factor that should be considered when biological limit values are developed.

PMID- 22421273
TI  - Arsenite exposure altered the expression of NMDA receptor and postsynaptic
      signaling proteins in rat hippocampus.
AB  - Chronic arsenic exposure has an adverse effect on neurobehavioral function. Our
      previous study demonstrated an elevated arsenic level, ultra-structure changes
      and reduced NR2A gene expression in hippocampus, and impaired spatial learning in
      arsenite-exposed rats. The NMDA receptor and the postsynaptic signaling proteins
      CaMKII, postsynaptic density protein 95 (PSD-95), synaptic Ras GTPase-activating
      protein (SynGAP) and nuclear activated extracellular-signal regulated kinase
      (ERK1/2) play important roles in synaptic plasticity, learning and memory. We
      hypothesized that the above molecular expression changes may contribute to
      arsenic neurotoxicity. In present study, the expression of NMDA receptor and
      postsynaptic signaling proteins in hippocampus were evaluated in rats exposed to
      0, 2.72, 13.6 and 68 mg/L sodium arsenite for 3 months. Decreased protein
      expression of NR2A, PSD-95 and p-CaMKII alpha in the hippocampus of arsenite
      exposed rats was observed, while the expression of SynGAP, a negative regulator
      of Ras-MAPK activity, was increased when compared with the controls.
      Additionally, decreased p-ERK1/2 activity was found in the hippocampus of
      arsenite-exposed rats. These data suggest that altered expression of NMDA
      receptor complex and postsynaptic signaling proteins may explain arsenic-induced
      neurotoxicity.

PMID- 22421274
TI  - Upward gaze and head deviation with frontal eye field stimulation.
AB  - Using electrical stimulation to the deep, most caudal part of the right frontal
      eye field (FEF), we demonstrate a novel pattern of vertical (upward) eye movement
      that was previously only thought possible by stimulating both frontal eye fields
      simultaneously. If stimulation was started when the subject looked laterally, the
      initial eye movement was back to the midline, followed by upward deviation. Our
      finding challenges current view of topological organisation in the human FEF and
      may have general implications for concepts of topological organisation of the
      motor cortex, since sustained stimulation also induced upward head movements as a
      component of the vertical gaze shift. [Published with video sequences].

PMID- 22421275
TI  - Tuberculosis: the drug development pipeline at a glance.
AB  - Tuberculosis is a major disease causing every year 1.8 million deaths worldwide
      and represents the leading cause of mortality resulting from a bacterial
      infection. Introduction in the 60's of first-line drug regimen resulted in the
      control of the disease and TB was perceived as defeating. However, since the
      progression of HIV leading to co-infection with AIDS and the emergence of drug
      resistant strains, the need of new anti-tuberculosis drugs was not overstated.
      However in the past 40 years any new molecule did succeed in reaching the market.
      Today, the pipeline of potential new treatments has been fulfilled with several
      compounds in clinical trials or preclinical development with promising activities
      against sensitive and resistant Mycobacterium tuberculosis strains. Compounds as
      gatifloxacin, moxifloxacin, metronidazole or linezolid already used against other
      bacterial infections are currently evaluated in clinical phases 2 or 3 for
      treating tuberculosis. In addition, analogues of known TB drugs (PA-824, OPC
      67683, PNU-100480, AZD5847, SQ609, SQ109, DC-159a) and new chemical entities
      (TMC207, BTZ043, DNB1, BDM31343) are under development. In this review, we report
      the chemical synthesis, mode of action when known, in vitro and in vivo
      activities and clinical data of all current small molecules targeting
      tuberculosis.

PMID- 22421276
TI  - Tyrosine modified analogues of the alpha4beta7 integrin inhibitor biotin-R8ERY
      prepared via Click Chemistry: synthesis and biological evaluation.
AB  - Our continuing programme aiming at developing inhibitors of integrin alpha4beta7,
      a key mediator of various inflammatory diseases, led us to synthesise a library
      of cell-permeable peptides based on the biotin-R(8)ERY(*) template, wherein the
      tyrosine residue has been modified by using the CuAAC reaction. The
      peptidomimetics were evaluated in a cell adhesion assay and shown to inhibit
      Mn(2+)-activated adhesion of mouse TK-1 T cells to mouse MAdCAM-1. Two of the
      synthesised peptidomimetics, analogues 11 and 14, are more active than our
      previously reported lead compound biotin-r(9)YDRREY at concentrations of 100 and
      50 MUM, with 14 exhibiting an IC(50) of less than 10 MUM.

PMID- 22421277
TI  - A new CERF board.

PMID- 22421278
TI  - Functional morphological imaging of autism spectrum disorders: current position
      and theories proposed.
AB  - Autism is a pervasive disorder of childhood development. Polymorphous clinical
      profiles combining various degrees of communication and social interaction with
      restricted and stereotyped behaviour are grouped under the heading of 'autism
      spectrum disorders' (ASD). Many teams are trying to pick out the underlying
      cerebral abnormalities in order to understand the neuronal networks involved in
      relationships with others. Here we review the morphological, spectroscopic and
      functional abnormalities in the amygdala-hippocampal circuit, the caudate nuclei,
      the cerebellum, and the frontotemporal regions, which have been described in
      subjects with ASD. White matter abnormalities have also been described in
      diffusion tensor imaging, leading to suspected damage to the subjacent neural
      networks, such as mirror neurones or the social brain.

PMID- 22421279
TI  - Diagnosis and radiological treatment of digestive haemorrhage following
      supramesocolic surgery.
AB  - Digestive haemorrhage following supramesocolic abdominal surgery (cephalic
      duodenopancreatectomy, cholecystectomy, total oesogastrectomy) is a rare but
      serious complication, which can be life-threatening. Improvement in scanning
      techniques has made it possible to modify the diagnostic strategy and improve the
      therapeutic management of the patients. The aim of this iconographic review is to
      recall the causes of digestive haemorrhage following supramesocolic surgery and
      to illustrate the dominant role of tomodensitometry in diagnosing it and in
      planning and controlling the efficacy of endovascular treatment.

PMID- 22421280
TI  - Applications of phase-contrast velocimetry sequences in cardiovascular imaging.
AB  - AIMS: To describe and illustrate the main applications of phase-contrast flow
      quantification in cardiovascular imaging. CONCLUSION: Phase-contrast velocimetry
      sequences provide an accurate, reliable, reproducible and non-invasive study of
      blood flow, information which is sometimes not available from other investigation
      methods. The haemodynamic information obtained from these complement MRI
      angiography images. They appear to have a range of clinical applications, firstly
      improving pathophysiological understanding but also contributing to the treatment
      and follow-up strategy after surgical or endovascular treatment.

PMID- 22421281
TI  - Magnetic resonance imaging in patellar lateral femoral friction syndrome (PLFFS):
      prospective case-control study.
AB  - OBJECTIVES: To describe morphologic abnormalities and signs of patellar lateral
      femoral friction syndrome (PLFFS) detected by magnetic resonance imaging (MRI).
      MATERIALS AND METHODS: Prospective study of 56 knees (21 patients and 30
      controls) studied by 3Tesla MRI. Comparative analysis of clinical data,
      quantitative and qualitative imaging criteria in a population of patients with
      anterior knee pain associated with an abnormal MRI signal along the lateral alar
      folds of the infrapatellar fat pad, a characteristic sign of PLFFS, and a control
      population with no anterior knee pain or abnormal signal from the infrapatellar
      fat pad. RESULTS: Patients with PLFFS have anterior and/or lateral knee pain.
      Their knee has anatomical predispositions for instability, primarily with patella
      alta (P<0.0001), patellar tilt more than 13.5 degrees  (P<0.0001), a patellar
      nose length less than 9 mm (P=0.0037), a patellar nose ratio less than 0.25
      (P<0.0001), a TT-TG distance more than 10 mm (P<0.0001), and a trochlear
      prominence more than 4 mm (P=0.0056). In 35% of patients, patellar chondropathy
      is visible, and 48% of patients have patellar or trochlear subchondral
      abnormalities. CONCLUSION: Anterior, lateral, and medial knee pain may be related
      to PLFFS. Anatomical predispositions contributing to instability are found in
      these patients. There may be associated chondropathies and osteochondropathies.

PMID- 22421282
TI  - Radiological features of triple-negative breast cancers (73 cases).
AB  - OBJECTIVES: Triple-negative breast cancers generally occur in young women and
      they have the potential to be aggressive. It is important for this subtype of
      tumour to be detected early. We studied the appearance of 73 tumours on
      mammography, sonography and MRI in order to determine what specific features they
      showed on imaging. PATIENTS AND METHODS: From July 2009 to December 2010, we
      retrospectively reviewed mammogram and sonogram images of 73 triple-negative
      cancers. Colour Doppler had been used to depict vascularisation in 34 cases and
      elastography score calculated in 17 cases. Sixteen patients had undergone MRI.
      The radiological description of these different modalities draws on the BI-RADS
      lexicon and categorisation. RESULTS: On mammography, triple-negative cancers
      often presented as a round mass (59.3%) or an oval or lobulated mass (65%), with
      circumscribed (15%), microlobulated (12.5%), indistinct (55%) or occasionally
      spiculated margins (15%). On sonography, the vast majority of these cancers
      appeared as masses (92.8%) with occasional posterior acoustic attenuation
      (22.6%). MRI showed more suspicious images than the standard examinations,
      notably rim-enhancement (eight out of 12 masses). CONCLUSION: . Radiological
      images appear as lobulated masses more readily, while on sonography posterior
      enhancement is shown more often than attenuation, and MRI finds rim-enhancement.

PMID- 22421283
TI  - Superinfection of focal liver lesions after bile duct procedures.
AB  - OBJECTIVES: Pyogenic liver abscess is a rare condition in the general population.
      The source of infection is most often biliary, and more rarely gastrointestinal
      via the portal tract, or even hematogenic. Other than in special contexts
      (scarring after radiofrequency ablation), focal liver lesions are not a usual
      risk factor for hepatic abscesses in patients with a history of bile duct
      procedures (sphincterotomy, biliary stenting, biliary enteric anastomosis).
      MATERIALS AND METHOD - RESULTS: We report four cases of focal liver lesions (two
      patients with benign lesions of the biliary cyst type and two other patients with
      lesions due to pancreatic cancer) complicated by a superinfection in patients
      with a history of bile duct procedures. There were no predisposing factors other
      than a context of cancer or diabetes. CONCLUSION: Superinfection of a focal liver
      lesion should be considered when there is a suggestive clinical picture and a
      change in the appearance of the lesion in patients with a history of bile duct
      procedures in a context of cancer or diabetes.

PMID- 22421284
TI  - Squamous cell carcinoma "mimicking" passive atelectasis from thoracic aortic
      aneurysm compression.

PMID- 22421285
TI  - A desmoid tumour associated with a breast prosthesis.

PMID- 22421286
TI  - Retroperitoneal extra-adrenal myelolipoma: appearance in CT and MRI.

PMID- 22421287
TI  - Radiologic-pathologic comparison of undifferentiated embryonal sarcoma of the
      liver in a 61-year-old woman.

PMID- 22421288
TI  - Giant aneurysm of the thoracic aorta. Answer to January e-quid.

PMID- 22421290
TI  - The diagnostic value of indirect ultrasound signs during acute adult
      appendicitis.
AB  - PURPOSE: To evaluate the diagnostic value of indirect ultrasound signs during
      acute appendicitis. PATIENTS AND METHODS: Our retrospective study lasted 5 years,
      from May 2005 to April 2010. It concerned 620 cases of appendectomy performed
      following prior ultrasound examination of the right iliac fossa (RIF). In 448
      cases, ultrasonography clearly showed the appendix, which was inflamed. The
      presence of indirect signs of appendix inflammation without visualisation of the
      appendix was confirmed by ultrasound examination in 160 cases. In 12 cases, the
      appendix was not visualised nor were there any indirect signs on the ultrasound
      image. The indirect signs involved were hypertrophy of the peritoneal fat (HPF),
      pain caused by compression on exploration of the right iliac fossa, and localised
      hypokinesia in the digestive loops (LHL). We compared the results found by
      ultrasonography with the operative and anatomical pathology reports. RESULTS: The
      positive predictive value of the indirect signs of appendicitis on the ultrasound
      scan was 95.8% if the three indirect signs were associated, 87.5% for the
      association of pain and HPF, 45.8% for the association of pain and LHL, and 25%
      if there was just pain. The negative predictive value of the indirect signs of
      appendicitis on the ultrasound scan was 57.2% if the three signs were associated,
      65.9% for the association of pain and HPF and 60.7% for the association of pain
      and LHL, with 83.3% for pain alone. The sensitivity of the indirect signs was
      83.9% if the three signs were associated, 31.8% for the association of pain and
      HPF, 50% for the association of pain and LHL, and 50% if there was just pain. The
      specificity of the indirect signs was 85.7% if the three signs were associated,
      96.7% for the association of pain and HPF, 56.7% for the association of pain and
      LHL, and 62.5% if there was just pain. CONCLUSION: When tomodensitometry cannot
      be performed and the appendix is not visible on ultrasound examination, indirect
      ultrasound signs must be systematically sought, particularly in populations in
      which appendicitis are highly prevalent.

PMID- 22421291
TI  - Mucosal disorders with oral epithelial dysplasia risk--development of a simple
      screening tool for general health care setting.
AB  - OBJECTIVES: Oral visual screening can avert oral cancer mortality. Oral
      premalignancies are currently considered as separate, individual disorders. The
      objective was to develop a simple clinical screening tool to detect oral
      premalignancies in general health care setting and validate diagnostic accuracy
      against Oral Medicine specialist examination as gold standard. MATERIALS AND
      METHODS: All steps in development of new tool, from item generation to item
      selection and item reduction were carried out. Item generation was done using
      qualitative methods. After pre-testing and piloting, junior dental house surgeon
      administered the refined tool, to patients attending dental outpatient department
      (n=255). Subsequent evaluation by an Oral Medicine specialist using consensus
      clinical criteria, detected 59 screen positive cases. Each case was recoded as
      per scores assigned by binary logistic regression coefficients and total score
      computed. The Receiver Operator Characteristic (ROC) was performed against
      specialist examination as gold standard. Performance ability and reliability
      coefficient of final tool was assessed. A simple score was assigned to indicate
      stage and clinical severity. RESULTS: Screening Tool for Oral Premalignancies
      (STOP) has sensitivity 96.6%, specificity 99.0% and accuracy 98.4% with
      reliability coefficient 0.874. Scores detect clinical signs and staging reflect
      clinical severity alerts. CONCLUSION: Oral Potentially Malignant Disorders need
      to be evaluated as single entity, under a common umbrella - Mucosal Disorders
      with Oral Epithelial Dysplasia risk (MD-OEDr). STOP is a simple tool for
      opportunistic general health care screening of MD-OEDr.

PMID- 22421292
TI  - Comment on "Tumour infiltration depth P4 mm is an indication for an elective neck
      dissection in pT1cN0 oral squamous cell carcinoma" by Melchers et al., Oral Oncol
      2012;48(4):337-42.

PMID- 22421293
TI  - A slowly growing plaque on the lower back:  answer.

PMID- 22421294
TI  - A case of a primary cutaneous plasmacytoma presenting in adolescence.
AB  - Primary cutaneous plasmacytoma is defined as monoclonal proliferation of plasma
      cells that arises primarily in the skin without evidence of systemic disease. We
      present an extremely rare case of a young adult diagnosed with solitary
      plasmacytoma. A 20-year-old woman presented with a pruritic erythematosquamous
      indurated plaque on the inner aspect of her right thigh. She had undergone a
      biopsy 5 years ago, and under the diagnosis of Nekam disease, she was treated
      with topical steroids followed by intralesional injections of triamcinolone
      acetonide. A new skin biopsy revealed infiltration of the epidermis by small T
      lymphocytes while plasma cell accumulations were found in the dermis.
      Immunostains for light and heavy chains [kappa, lambda, immunoglobulin (Ig) G,
      IgA, and IgM] demonstrated IgG/kappa monoclonality of the plasma cells. On
      molecular analysis, T-cell receptor and immunoglobulin heavy chain rearrangements
      were polyclonal. Serum protein electrophoresis, immunofixation, and quantitative
      assessment of serum Igs were normal. Bone marrow biopsy, skeletal survey, and
      body computed tomography scan were unremarkable. A diagnosis of primary solitary
      cutaneous plasmacytoma was made. The lesion was removed surgically, and the
      patient remains in remission up to now. Primary cutaneous plasmacytoma represents
      only 2%-4% of extramedullary plasmacytomas. The rarity and the nonspecific
      presentation of cutaneous plasmacytomas does not allow a definite clinical
      diagnosis. Only histopathology reveals the typical pattern of a dense monomorphic
      dermal plasmacytic infiltrate, whereas immunohistochemistry shows monoclonality
      of the neoplastic cells.

PMID- 22421295
TI  - Cutaneous clear cell sarcoma:  report of three cases of a potentially
      underestimated mimicker of spindle cell melanoma.
AB  - Clear cell sarcoma is a unique soft tissue tumor with distinct microscopic
      features that include a nested or fascicular pattern of spindle cells accompanied
      by larger wreath-like giant cells scattered throughout. It harbors a unique EWSR1
      ATF1 gene fusion secondary to a t(12;22)(q13;q12) translocation. Recently, it was
      reported that clear cell sarcoma can occur in the skin and mimic a broad spectrum
      of entities, including spindle cell melanoma. Here, we describe 3 new cases of
      clear cell sarcoma of the skin, all of which were confirmed molecularly. The
      patients, a 12-year-old boy, a 29-year-old woman, and a 60-year-old man, had
      cutaneous lesions on the thigh, dorsum of foot, and sole, respectively. All 3
      lesions were originally considered suspicious of spindle cell melanoma.
      Microscopically, the lesions featured nodular proliferation centered in the
      dermis that consisted of discrete fascicles of spindle cell enmeshed by thin
      fibrous strands. Wreath-like cells were present in all cases. Tumor cells were
      positive for S100 protein (3 of 3 cases), melan A (2 of 3 cases), HMB 45 (1 of 3
      cases) although a junctional melanocytic proliferation was seen in 1 case.
      Sentinel lymph node biopsy was negative in 2 patients. Follow-up was uneventful
      in 2 patients, whereas the other patient developed a lymph node metastasis 5
      months after primary tumor excision. This study confirms that malignant dermal
      tumors that mimic but do not exactly replicate spindle cell melanoma should raise
      suspicion for cutaneous clear cell sarcoma and prompt the investigation for the
      confirmatory gene fusion t(12;22).

PMID- 22421296
TI  - Low clinically significant rate of recurrence in benign nevi.
AB  - The recurrence rate of benign nevi has been infrequently reported and primarily
      as a rate of clinical recurrence. The aim of this study was to document the rate
      of recurrence leading to re-excision of previously biopsied nevi (the clinically
      significant recurrence rate). Nevi undergoing primary biopsy with a minimum 5
      years follow-up were reviewed in a pathology database for recurrence requiring a
      further excision. A total of 1035 nevi were reviewed including 196 dysplastic
      nevi. Twenty six percent of nevi had a positive margin, more common in shave and
      punch than ellipse biopsied lesions. Three cases recurred requiring re-excision
      resulting in a pathology recurrence rate of 0.3%. These 3 cases showed benign
      changes and 2 were originally excised with clear margins. The rate of recurrence
      requiring re-excision is very low at 0.3%. This suggests that few cases of
      clinical recurrence are re-excised. Re-excision of benign nevi including mild and
      moderately dysplastic nevi may not be necessary.

PMID- 22421297
TI  - Ex vivo dermoscopy of cutaneous biopsies for melanocytic neoplasms:  a
      retrospective review of 517 cases with histopathologic correlation.
AB  - Clinical dermoscopy has provided new insights into the diagnosis and
      classification of melanocytic neoplasms. There are only limited data on its
      applications in dermatopathology. In our laboratory, we routinely photograph all
      skin biopsies with ex vivo dermoscopy (EVD). We retrospectively reviewed 517
      cutaneous biopsies with corresponding EVD images to determine whether EVD
      provides useful ancillary information in the histopathologic diagnosis of
      melanocytic neoplasms. Four hundred eighty-three cases (93.4%) yielded usable
      images. The lesions could be categorized according to a published dermoscopic
      classification system of melanocytic proliferations. Reticular pigmentation
      correlated with dysplastic nevi, globular pigmentation with congenital nevi,
      homogenous blue pigmentation with blue nevi, starburst peripheral globular
      pigmentation with Spitz nevi, and atypical pigment patterns with melanoma.
      Eighteen of 25 cases (72%) with ambiguous histopathology were assigned a more
      definite diagnosis when reviewed contemporaneously with EVD images. The surgical
      margins in 40 cases (7.7%) were reclassified when EVD images were included in the
      review. We found EVD to be a useful technique and advocate its use for diagnosis
      and clinical-pathologic correlation.

PMID- 22421298
TI  - Functional measurement of coronary stenosis.
AB  - Fractional flow reserve (FFR) is considered nowadays as the gold standard for
      invasive assessment of physiologic stenosis significance and an indispensable
      tool for decision making in coronary revascularization. Use of FFR in the
      catheterization laboratory accurately identifies which lesions should be stented
      and improves the outcome in most elective clinical and angiographic conditions.
      Recently, FFR has been upgraded to a class IA classification in multivessel
      percutaneous coronary intervention in the guidelines on coronary
      revascularization of the European Society of Cardiology. In this state-of-the-art
      paper, the basic concept of FFR and its application, characteristics, and use in
      several subsets of patients are discussed from a practical point of view.

PMID- 22421300
TI  - Diagnosis of spontaneous coronary artery dissection by optical coherence
      tomography.
AB  - OBJECTIVES: This study sought to assess the diagnostic value of optical coherence
      tomography (OCT) in patients with suspected spontaneous coronary artery
      dissection (SCAD). BACKGROUND: SCAD is a rare but challenging clinical entity.
      METHODS: Following a prospective protocol, OCT was performed in 17 consecutive
      patients with a clinical and angiographic suspicion of SCD from a total of 5,002
      patients undergoing coronary angiography. A conservative management strategy was
      followed. RESULTS: OCT ruled out the diagnosis of SCAD in 6 patients with
      coronary artery disease (atherosclerotic plaques and/or intracoronary thrombus).
      In 11 patients (age 48 +/- 9 years, 9 female), OCT confirmed the presence of
      SCAD. A double-lumen or intramural hematoma image was visualized in all cases.
      However, only 3 patients presented an intimal "flap" on angiography. OCT readily
      identified the intimal rupture site (n = 7), the thickness (348 +/- 84 MUm) and
      length (31 +/- 9 mm) of the intimomedial membrane, the area of the true (1.1 +/-
      0.5 mm(2)) and false lumen (5.9 +/- 2.1 mm(2)), the associated intramural
      hematoma (n = 9), and thrombi in the true or false lumens (n = 11). Most of these
      findings were angiographically silent. After stenting (n = 4), OCT disclosed
      adequate stent coverage, expansion, and apposition, but also residual intramural
      hematoma at the stented site (abluminal) and at the distal vessel. CONCLUSIONS:
      OCT provides unique insights in patients with SCAD that allow an early diagnosis
      and adequate management. Most of these findings are undetectable by angiography.

PMID- 22421299
TI  - Consensus standards for acquisition, measurement, and reporting of intravascular
      optical coherence tomography studies: a report from the International Working
      Group for Intravascular Optical Coherence Tomography Standardization and
      Validation.
AB  - OBJECTIVES: The purpose of this document is to make the output of the
      International Working Group for Intravascular Optical Coherence Tomography (IWG
      IVOCT) Standardization and Validation available to medical and scientific
      communities, through a peer-reviewed publication, in the interest of improving
      the diagnosis and treatment of patients with atherosclerosis, including coronary
      artery disease. BACKGROUND: Intravascular optical coherence tomography (IVOCT) is
      a catheter-based modality that acquires images at a resolution of ~10 MUm,
      enabling visualization of blood vessel wall microstructure in vivo at an
      unprecedented level of detail. IVOCT devices are now commercially available
      worldwide, there is an active user base, and the interest in using this
      technology is growing. Incorporation of IVOCT in research and daily clinical
      practice can be facilitated by the development of uniform terminology and
      consensus-based standards on use of the technology, interpretation of the images,
      and reporting of IVOCT results. METHODS: The IWG-IVOCT, comprising more than 260
      academic and industry members from Asia, Europe, and the United States, formed in
      2008 and convened on the topic of IVOCT standardization through a series of 9
      national and international meetings. RESULTS: Knowledge and recommendations from
      this group on key areas within the IVOCT field were assembled to generate this
      consensus document, authored by the Writing Committee, composed of academicians
      who have participated in meetings and/or writing of the text. CONCLUSIONS: This
      document may be broadly used as a standard reference regarding the current state
      of the IVOCT imaging modality, intended for researchers and clinicians who use
      IVOCT and analyze IVOCT data.

PMID- 22421301
TI  - Morphometric assessment of coronary stenosis relevance with optical coherence
      tomography: a comparison with fractional flow reserve and intravascular
      ultrasound.
AB  - OBJECTIVES: The study sought to assess the diagnostic efficiency of optical
      coherence tomography (OCT) in identifying hemodynamically severe coronary
      stenoses as determined by fractional flow reserve (FFR). Concomitant OCT and
      intravascular ultrasound (IVUS) area measurements were performed in a subgroup of
      patients to compare the diagnostic efficiency of both techniques. BACKGROUND: The
      value of OCT to determine stenosis severity remains unsettled. METHODS: Sixty-one
      stenoses with intermediate angiographic severity were studied in 56 patients.
      Stenoses were labeled as severe if FFR <=0.80. OCT interrogation was performed in
      all cases, with concomitant IVUS imaging in 47 cases. RESULTS: Angiographic
      stenosis severity was 50.9 +/- 8% diameter stenosis with 1.28 +/- 0.3 mm minimal
      lumen diameter. FFR was <=0.80 in 28 (45.9%) stenoses. An overall moderate
      diagnostic efficiency of OCT was found (area under the curve [AUC]: 0.74; 95%
      confidence interval [CI]: 0.61 to 0.84), with sensitivity/specificity of 82%/63%
      associated with an optimal cutoff value of 1.95 mm(2). Comparison of the results
      in patients with simultaneous IVUS and OCT imaging revealed no significant
      differences in the diagnostic efficiency of OCT (AUC: 0.70; 95% CI: 0.55 to 0.83)
      and IVUS (AUC. 0.63; 95% CI: 0.47 to 0.77; p = 0.19). Sensitivity/specificity for
      IVUS was 67%/65% for an optimal cutoff value of 2.36 mm(2). In the subgroup of
      small vessels (reference diameter <3 mm) OCT showed a significantly better
      diagnostic efficiency (AUC: 0.77; 95% CI: 0.60 to 0.89) than IVUS (AUC: 0.63; 95%
      CI: 0.46 to 0.78) to identify functionally significant stenoses (p = 0.04).
      CONCLUSIONS: OCT has a moderate diagnostic efficiency in identifying
      hemodynamically severe coronary stenoses. Although OCT seems slightly superior to
      IVUS for this purpose (particularly in vessels <3 mm), its low specificity
      precludes its use as a substitute of FFR for functional stenosis assessment.

PMID- 22421302
TI  - The clinical emergence of optical coherence tomography: defining a role in
      intravascular imaging.

PMID- 22421303
TI  - Randomized trial of optimal treatment strategies for in-stent restenosis after
      drug-eluting stent implantation.
AB  - OBJECTIVES: The purpose of this study is to compare the efficacy of the treatment
      strategies for in-stent restenosis (ISR) of drug-eluting stents (DES) according
      to the morphologic pattern of restenosis. BACKGROUND: Optimal treatment
      strategies for ISR within DES have not been adequately addressed yet. METHODS:
      Patients with ISR of DES were randomized according to the lesion length to
      compare outcomes of sirolimus-eluting stent (SES) versus cutting balloon
      angioplasty for focal type (<=10 mm) and SES versus everolimus-eluting stent
      (EES) for diffuse type (>10 mm). The primary endpoint was in-segment late loss at
      9 months. Overall 162 patients, 96 with focal ISR and 66 with diffuse ISR, were
      enrolled. RESULTS: In focal lesions, in-segment late loss was significantly
      higher in the cutting balloon group (n = 48) than in the SES group (n = 48; 0.25
      mm, interquartile range [IQR]: -0.01 to 0.68 mm vs. 0.06 mm, IQR: -0.08 to 0.17
      mm; p = 0.04). Consequently, in-segment restenosis rate tended to be higher in
      the cutting balloon group than in the SES group (20.7% vs. 3.1%, p = 0.06) with
      comparable incidences of the composite of death, myocardial infarction, or target
      vessel revascularization at 12 months of clinical follow up (6.3% vs. 6.3%, p >
      0.99). In 66 cases of diffuse ISR, in-segment late loss (0.11 mm, IQR: -0.02 to
      0.30 mm; vs. 0.00 mm, IQR: -0.08 to 0.25 mm; p = 0.64), in-segment restenosis
      rate (5.0% vs. 14.3%, p = 0.32), and the composite incidence of death, myocardial
      infarction, or target lesion revascularization (9.6% vs. 8.8%, p > 0.99) did not
      differ between SES group (n = 32) and EES group (n = 34). CONCLUSIONS: For
      lesions of focal DES restenosis, repeat implantation of SES is more effective in
      reducing late luminal loss and subsequent restenosis rate than cutting balloon
      angioplasty. For diffuse DES restenosis, implantation of SES or EES is comparably
      effective in terms of angiographic and clinical outcomes.

PMID- 22421305
TI  - Mechanical aortic valve replacement in young women planning on pregnancy:
      maternal and fetal outcomes under low oral anticoagulation, a pilot observational
      study on a comprehensive pre-operative counseling protocol.
AB  - OBJECTIVES: This pilot prospective observational study aimed to evaluate the
      maternal and fetal outcomes of pregnancies under low-dose oral anticoagulation
      therapy after aortic mechanical replacement. BACKGROUND: Need for valve
      replacement is still an issue for young women with native valve disease who are
      planning on future pregnancy. Choice of replacement device is a challenging
      clinical task. METHODS: A comprehensive pre-operative counseling protocol to
      guide choice of replacement device was developed. The pre-operative
      anticoagulation trial to determine the warfarin daily dosage needed to reach
      target international normalized ratio (INR) represented the main stem of such
      protocol. Pregnancies on low-dose anticoagulation therapy (target INR: 1.5 to
      2.5) were allowed in a highly selected subset of mechanical aortic valve
      recipients. RESULTS: Twenty-two patients of 40 originally referred for native
      valve disease surgery requiring valve replacement, safely underwent the pre
      operative anticoagulation challenge. No maternal or fetal complications were
      detected in 16 pregnancies under low oral anticoagulation. Patterns of warfarin
      daily dosage and induced INRs were characterized during pregnancy. CONCLUSIONS:
      In this small sample observational study, a pre-operative anticoagulation therapy
      trial helped young women scheduled for valve replacement to acquire complete
      information as to the choice of prosthetic device. In selected third-generation
      mechanical aortic prosthesis recipients, low-dose anticoagulation therapy seems
      safe and feasible for both mother and fetus. Further studies are needed to
      validate this approach.

PMID- 22421304
TI  - Plasma neutrophil gelatinase-associated lipocalin is independently associated
      with cardiovascular disease and mortality in community-dwelling older adults: The
      Rancho Bernardo Study.
AB  - OBJECTIVES: The purpose of this study was to determine the association between
      neutrophil gelatinase-associated lipocalin (NGAL) levels and cardiovascular and
      all-cause mortality in community-dwelling older adults. BACKGROUND: NGAL is a
      novel marker best known for its role in rapidly identifying acute kidney injury.
      Although expressed in atherosclerosis, its association with cardiovascular
      disease (CVD) in the community has not been reported. METHODS: We measured plasma
      NGAL levels in 1,393 Rancho Bernardo Study participants without CVD, mean age 70
      years. Participants were followed for a mean time period of 11 years. RESULTS:
      During follow-up, 436 participants died (169 from CVD). In models adjusted for
      traditional CVD risk factors and creatinine clearance, NGAL was a significant
      predictor of CVD mortality (hazard ratio [HR] per SD log increase: 1.33, 95%
      confidence interval [CI]: 1.12 to 1.57), all-cause mortality (HR: 1.19, 95% CI:
      1.07 to 1.32), and a combined cardiovascular endpoint (HR: 1.26, 95% CI: 1.10 to
      1.45). After further adjusting for N-terminal pro-B-type natriuretic peptide (NT
      proBNP) and C-reactive protein (CRP), NGAL remained an independent predictor of
      each outcome. NGAL improved the C-statistic (0.835 to 0.842) for prediction of
      CVD death (p = 0.001). Net reclassification improvement (>0) with the addition of
      NGAL was 18% (p = 0.02); the integrated discrimination index was also significant
      (p = 0.01). Participants with NGAL and NT-proBNP above the median had increased
      risk of CVD death versus those with only NT-proBNP elevated (HR: 1.43, 95% CI:
      1.12 to 1.82). CONCLUSIONS: Plasma NGAL is a significant predictor of mortality
      and CVD in community-dwelling older adults, independent of traditional risk
      factors and kidney function, and adds incremental value to NT-proBNP and CRP. The
      potential impact of these results includes providing insight into new mechanisms
      of CVD and the possibility of improving screening, intervention, and prevention.

PMID- 22421306
TI  - The search for a safe and effective anticoagulation regimen in pregnant women
      with mechanical prosthetic heart valves.

PMID- 22421307
TI  - Platelet disaggregation after coronary stent thrombosis.

PMID- 22421308
TI  - Adherence, compliance, concordance, or the lack thereof.

PMID- 22421309
TI  - Delayed contrast-enhanced magnetic resonance imaging in the evaluation of
      Takayasu arteritis.

PMID- 22421310
TI  - Reverse freeze casting: a new method for fabricating highly porous titanium
      scaffolds with aligned large pores.
AB  - Highly porous titanium with aligned large pores up to 500 MUm in size, which is
      suitable for scaffold applications, was successfully fabricated using the reverse
      freeze casting method. In this process we have newly developed, the Ti powders
      migrated spontaneously along the pre-aligned camphene boundaries at a temperature
      of 45.5 degrees C and formed a titanium-camphene mixture with an aligned
      structure; this was followed by freeze drying and sintering. As the casting time
      increased from 24 to 48 h, the initial columnar structures turned into lamellar
      structures, with the porosity decreasing from 69 to 51%. This reduction in
      porosity caused the compressive yield strength to increase from 121 to 302 MPa,
      with an elastic modulus of the samples being in the range of 2-5 GPa. In
      addition, it was demonstrated that reverse freeze casting can also be
      successfully applied to various other raw powders, suggesting that the method
      developed in this work opens up new avenues for the production of a range of
      porous metallic and ceramic scaffolds with highly aligned pores.

PMID- 22421311
TI  - Development of silk-based scaffolds for tissue engineering of bone from human
      adipose-derived stem cells.
AB  - Silk fibroin is a potent alternative to other biodegradable biopolymers for bone
      tissue engineering (TE), because of its tunable architecture and mechanical
      properties, and its demonstrated ability to support bone formation both in vitro
      and in vivo. In this study, we investigated a range of silk scaffolds for bone TE
      using human adipose-derived stem cells (hASCs), an attractive cell source for
      engineering autologous bone grafts. Our goal was to understand the effects of
      scaffold architecture and biomechanics and use this information to optimize silk
      scaffolds for bone TE applications. Silk scaffolds were fabricated using
      different solvents (aqueous vs. hexafluoro-2-propanol (HFIP)), pore sizes (250
      500 MUm vs. 500-1000 MUm) and structures (lamellar vs. spherical pores). Four
      types of silk scaffolds combining the properties of interest were systematically
      compared with respect to bone tissue outcomes, with decellularized trabecular
      bone (DCB) included as a "gold standard". The scaffolds were seeded with hASCs
      and cultured for 7 weeks in osteogenic medium. Bone formation was evaluated by
      cell proliferation and differentiation, matrix production, calcification and
      mechanical properties. We observed that 400-600 MUm porous HFIP-derived silk
      fibroin scaffold demonstrated the best bone tissue formation outcomes, as
      evidenced by increased bone protein production (osteopontin, collagen type I,
      bone sialoprotein), enhanced calcium deposition and total bone volume. On a
      direct comparison basis, alkaline phosphatase activity (AP) at week 2 and new
      calcium deposition at week 7 were comparable to the cells cultured in DCB. Yet,
      among the aqueous-based structures, the lamellar architecture induced increased
      AP activity and demonstrated higher equilibrium modulus than the spherical-pore
      scaffolds. Based on the collected data, we propose a conceptual model describing
      the effects of silk scaffold design on bone tissue formation.

PMID- 22421313
TI  - Prostate cancer stem cells.
AB  - Stem cells have long been implicated in prostate gland formation. The prostate
      undergoes regression after androgen deprivation and regeneration after
      testosterone replacement. Regenerative studies suggest that these cells are found
      in the proximal ducts and basal layer of the prostate. Many characteristics of
      prostate cancer indicate that it originates from stem cells. For example, the
      putative androgen receptor-negative (AR(-)) status of prostate stem cells renders
      them inherently insensitive to androgen blockade therapy. The androgen-regulated
      gene fusion TMPRSS2-ERG could be used to clarify both the cells of origin and the
      evolution of prostate cancer cells. In this review, we show that the hypothesis
      that distinct subtypes of cancer result from abnormalities within specific cell
      types-the stem cell theory of cancer-may instigate a major paradigm shift in
      cancer research and therapy. Ultimately, the stem cell theory of cancers will
      affect how we practice clinical oncology: our diagnosis, monitoring, and therapy
      of prostate and other cancers.

PMID- 22421312
TI  - Postnatal exposure to trichloroethylene alters glutathione redox homeostasis,
      methylation potential, and neurotrophin expression in the mouse hippocampus.
AB  - Previous studies have shown that continuous exposure throughout gestation until
      the juvenile period to environmentally relevant doses of trichloroethylene (TCE)
      in the drinking water of MRL+/+ mice promoted adverse behavior associated with
      glutathione depletion in the cerebellum indicating increased sensitivity to
      oxidative stress. The purpose of this study was to extend our findings and
      further characterize the impact of TCE exposure on redox homeostasis and
      biomarkers of oxidative stress in the hippocampus, a brain region prone to
      oxidative stress. Instead of a continuous exposure, the mice were exposed to
      water only or two environmentally relevant doses of TCE in the drinking water
      postnatally from birth until 6 weeks of age. Biomarkers of plasma metabolites in
      the transsulfuration pathway and the transmethylation pathway of the methionine
      cycle were also examined. Gene expression of neurotrophins was examined to
      investigate a possible relationship between oxidative stress, redox imbalance and
      neurotrophic factor expression with TCE exposure. Our results show that
      hippocampi isolated from male mice exposed to TCE showed altered glutathione
      redox homeostasis indicating a more oxidized state. Also observed was a
      significant, dose dependent increase in glutathione precursors. Plasma from the
      TCE treated mice showed alterations in metabolites in the transsulfuration and
      transmethylation pathways indicating redox imbalance and altered methylation
      capacity. 3-Nitrotyrosine, a biomarker of protein oxidative stress, was also
      significantly higher in plasma and hippocampus of TCE-exposed mice compared to
      controls. In contrast, expression of key neurotrophic factors in the hippocampus
      (BDNF, NGF, and NT-3) was significantly reduced compared to controls. Our results
      demonstrate that low-level postnatal and early life TCE exposure modulates
      neurotrophin gene expression in the mouse hippocampus and may provide a mechanism
      for TCE-mediated neurotoxicity.

PMID- 22421314
TI  - Increased expression of the spliced DDR1c isoform in brain tissues from
      schizophrenia patients.

PMID- 22421315
TI  - Use of multiple pedagogies to promote confidence in triage decision making: a
      pilot study.
AB  - BACKGROUND: The purpose of this pilot study was to determine whether the addition
      of educational interventions to required clinical hours promotes confidence in
      triage decision making among nursing students enrolled in a final capstone
      course. METHODS: An experimental design was implemented with randomization of
      students (n = 14) to 1 of 3 intervention groups or the control group. The Triage
      Decision Making Inventory was used as a pretest-posttest. Educational strategies
      implemented included an Advanced Cardiac Life Support course and simulations with
      debriefing. Interventions were in addition to required clinical hours. RESULTS: A
      mixed analysis of variance was used to examine the 4 groups by time, with all
      groups exhibiting higher scores on the Triage Decision Making Inventory from the
      pretest to the posttest (F (3, 10) = 4.51, P = .03 (eta(2) = .575). Students who
      received both the simulations and the Advanced Cardiac Life Support course
      demonstrated a significant difference across time. CONCLUSIONS: As nursing
      education evolves with the integration of technology, the combination of multiple
      pedagogies also can enhance confidence in triage decision making among
      experienced and novice nurses in emergency settings.

PMID- 22421316
TI  - How much and where: assessment of knowledge level of the application of cricoid
      pressure.
AB  - INTRODUCTION: Application of cricoid pressure is a frequently used technique in
      both rapid sequence intubation in multiple settings and in a more controlled
      setting in the operating room. In a survey of emergency department personnel
      performed at the University of Michigan, it was found that there is a knowledge
      deficit in the recommended force and the anatomic localization of cricoid
      pressure. Participants in the original study, which included emergency nurses,
      medical residents, and attending physicians, rated their training in cricoid
      pressure as poor or nonexistent. A review of the literature shows that, although
      cricoid pressure is used during endotracheal intubation to protect against
      regurgitation of gastric contents, many people applying cricoid pressure do not
      have a good knowledge of where to apply the pressure or how much pressure to
      apply to be effective. Because cricoid pressure is applicable in areas other than
      the emergency department, our study surveys personnel in emergency medical
      services/flight crew; emergency, intensive care unit, and operating room nurses;
      and respiratory therapists. Even though the use of cricoid pressure is no longer
      recommended, it is still routinely used. Although applying cricoid pressure is a
      simple procedure, persons using it must be thoroughly trained and retrained to
      prevent complications. METHODS: When we replicated the University of Michigan
      study at a 254-bed tertiary care facility, a potential of 325 staff members were
      given access to an online survey using the questions in the original survey.
      Staff were assigned to a HealthStream module and sent an invitation through their
      employee e-mail account. The module included a link to the questionnaire, and
      demographic data were gathered. The module was optional and results confidential.
      RESULTS: Operating room nurses were most likely to receive supervised instruction
      on anesthetized patients. These operating room nurses also showed the highest
      overall knowledge level about the application technique of cricoid pressure.
      DISCUSSION: There continues to be a lack of knowledge about the application of
      cricoid pressure during intubation. There is an opportunity for collaboration
      between staff and academic educators to allow for additional theoretical as well
      as hands-on practice.

PMID- 22421317
TI  - Stroke Health and Risk Education (SHARE): design, methods, and theoretical basis.
AB  - BACKGROUND: Stroke is a disease with tremendous individual, family, and societal
      impact across all race/ethnic groups. Mexican Americans, the largest subgroup of
      Hispanic Americans, are at even higher risk of stroke than European Americans.
      AIM: To test the effectiveness of a culturally sensitive, church-based, multi
      component, motivational enhancement intervention for Mexican Americans and
      European Americans in reducing stroke risk factors. METHODS: Participants enroll
      in family or friendship pairs, from the same Catholic church in the Corpus
      Christi Texas area, and are encouraged to change diet and physical activity
      behaviors and provide support for behavior change to their partners. Churches are
      randomized to either the intervention or control group. Goal enrollment for each
      of the 10 participating churches is 40 participant pairs. The intervention
      consists of self-help materials (including a motivational short film,
      cookbook/healthy eating guide, physical activity guide with pedometer, and
      photonovella), five motivational interviewing calls, two tailored newsletters,
      parish health promotion activities and environmental changes, and a peer support
      workshop where participants learn to provide autonomy supportive counseling to
      their partner. SHARE's three primary outcomes are self-reported sodium intake,
      fruit and vegetable intake, and level of physical activity. Participants complete
      questionnaires and have measurements at baseline, six months, and twelve months.
      Persistence testing is performed at 18 months in the intervention group. The
      trial is registered with clinicaltrials.gov (NCT01378780).

PMID- 22421318
TI  - Clinical significance of inflammatory and fibrogenic cytokines in diabetic
      nephropathy.
AB  - OBJECTIVES: To study the role of inflammatory chemokine; monocyte chemoattractant
      protein-1 (MCP-1), and fibrogenic markers [transforming growth factor beta-1 (TGF
      beta(1)), connective tissue growth factor (CTGF) and fibronectin (FN)] in
      diabetic nephropathy (DN). DESIGN AND METHODS: This study included 17 control and
      65 type 2 diabetic subjects (18 normoalbuminuric, 22 microalbuminuric and 25
      macroalbuminuric). Demographic characteristics, diabetic index and kidney
      function tests were monitored. Serum TGF-beta(1), plasma CTGF, MCP-1 and FN
      levels were assayed. RESULTS: Microalbuminuric and macroalbuminuric subjects
      showed a significant elevation in TGF-beta(1), CTGF, MCP-1 and FN levels as
      compared with control and normoalbuminuric subjects. There was positive
      correlation between these markers and fasting plasma glucose, albumin excretion
      rate and with each other. CONCLUSION: This study revealed the importance of these
      markers in DN pathogenesis which is powered by their association and thus the
      possibility of their use as biochemical markers in DN was suggested.

PMID- 22421319
TI  - Interactions of people with disabilities and nursing staff during
      hospitalization.
AB  - OBJECTIVE: Inadequate primary health care and screening have been identified as
      serious issues for people with disabilities, but little evidence exists on the
      nursing care of this population when hospitalized. This study sought to explore
      the experiences of people with disabilities in their interactions with nurses and
      unlicensed assistive personnel and their perceptions of the care they received
      during hospital stays. METHODS: In this descriptive qualitative study, 35 people
      with disabilities were interviewed in focus groups, and audio recordings of the
      interviews were transcribed and validated for accuracy. Content analysis
      identified major themes. RESULTS: Four themes were identified: poor communication
      on the part of nursing staff, compromised care, negative attitudes among staff,
      and participants' fears related to quality of care. CONCLUSIONS: The findings
      suggest the need for further research into the nursing care of people with
      disabilities during hospitalization. Educational strategies to ensure that nurses
      and unlicensed assistive personnel have adequate knowledge about the needs of
      people with disabilities may help in augmenting the care provided to this
      population.

PMID- 22421320
TI  - The underutilization of emergency contraception.
AB  - Despite the availability of effective contraceptive methods, unintended pregnancy
      continues to be a significant health problem for women throughout the world. The
      reasons for unplanned pregnancy include failure to use contraception, incorrect
      use of contraception, unplanned consensual intercourse, and rape. Emergency
      contraception was once heralded as a means of reducing the rates of unintended
      pregnancy, elective abortion, and unwanted childbirth. But more than three
      decades after the first oral form was introduced, the use of emergency
      contraception remains suboptimal-even in the United States, where it is available
      to most women of childbearing age without a prescription. Nurses can help narrow
      this clinical gap in women's health care by increasing awareness of emergency
      contraception, correcting common misconceptions about its mechanism of action and
      potential adverse effects, and facilitating patient access.

PMID- 22421321
TI  - Modification of the C16Y peptide on nanoparticles is an effective approach to
      target endothelial and cancer cells via the integrin receptor.
AB  - Liposomes have been explored as potential drug and gene-delivery particles. In
      recent years, tumor-targeted liposomes have been developed to improve the
      efficacy of antitumor treatment. The C16Y peptide is a modified C16 peptide,
      which is derived from the laminin gamma1 chain, and binds to integrins
      alpha(v)beta3 and alpha5beta1 on endothelial cells. In this study, we prepared
      integrin-targeted C16Y peptide-modified liposomes (C16Y-L) to enhance the
      intracellular uptake of drugs and genes specifically into tumor tissues. The
      selectivity of C16Y-L for endothelial cells and cancer cells, which strongly
      express integrins alpha(v)beta3 and alpha5beta1, was assessed by flow cytometry
      and confocal microscopy. The cellular uptake of C16Y-L by both cell types was
      higher than uptake of the un-labeled and scramble peptide-modified liposomes.
      Next, to ascertain the involvement of receptor-mediated endocytosis in the
      process, these cells were treated with C16Y-L for 1h at 37 degrees C or at 4
      degrees C. We found that uptake was also dependent on the temperature. Moreover,
      to evaluate whether the uptake depended on an integrin-ligand interaction, we
      examined the inhibition of C16Y-L uptake using recombinant integrin alphaVbeta3
      and found that the cellular uptake of C16Y-L treated with alphaVbeta3 integrin
      decreased. This result suggests that C16Y-L can selectively target cells that
      highly express integrin alphaVbeta3. Thus, the modification of the C16Y peptide
      on a Drug Delivery System (DDS) carrier may be a feasible approach for drug or
      gene delivery into tumors.

PMID- 22421322
TI  - Thiolated chitosan nanoparticles for the nasal administration of leuprolide:
      bioavailability and pharmacokinetic characterization.
AB  - The purpose of this study was to develop thiolated nanoparticles to enhance the
      bioavailability for the nasal application of leuprolide. Thiolated chitosan
      thioglycolic acid (chitosan-TGA) and unmodified chitosan nanoparticles (NPs) were
      developed via ionic gelation with tripolyphosphate (TPP). Leuprolide was
      incorporated during the formulation process of NPs. The thiolated (chitosan-TGA)
      NPs had a mean size of 252 +/- 82 nm, a zeta potential of +10.9 +/- 4 mV, and
      payload of leuprolide was 12 +/- 2.8. Sustained release of leuprolide from
      thiolated NPs was demonstrated over 6h, which might be attributed to inter-
      and/or intramolecular disulfide formation within the NPs network. Ciliary beat
      frequency (CBF) study demonstrated that thiolated NPs can be considered as
      suitable additives for nasal drug delivery systems. Compared to leuprolide
      solution, unmodified NPs and thiolated NPs provoked increased leuprolide
      transport through porcine nasal mucosa by 2.0 and 5.2 folds, respectively. The
      results of a pharmacokinetic study in male Sprague-Dawley rats showed improved
      transport of leuprolide from thiolated NPs as compared to leuprolide solution.
      Thiolated NPs had a 6.9-fold increase in area under the curve, more than 4-fold
      increase in elimination half-life, and a ~3.8-fold increase in maximum plasma
      concentration compared to nasal solution alone. The relative nasal
      bioavailability (versus s.c. injection) of leuprolide thiolated NPs calculated on
      the basis of AUC((0-6)) was about 19.6% as compared to leuprolide solution 2.8%.
      The enhanced bioavailability of leuprolide is likely due to facilitated transport
      by thiolated NPs rather than improved release.

PMID- 22421323
TI  - Acute pathophysiological influences of conducted electrical weapons in humans: A
      review of current literature.
AB  - Conducted electrical weapons (CEWs) deliver short high-voltage, low current
      energy pulses to temporarily paralyze a person by causing muscular contraction.
      The narrative of this article is a methodical analysis on acute
      pathophysiological changes within the central nervous system, cardiovascular,
      neuroendocrine, sympatho-adrenergic and muskuloskeletal system which can occur
      after application of conducted electrical weapons on human subjects. The results
      are based on wide-ranging literature analysis and source studies. The majority of
      the recent scientific publications on humans classify the health risks of an
      appropriate use of the CEWs device as minor. However, there still is an
      uncertainty about possible side-effects of these devices. Therefore medical
      supervision with human application is advised.

PMID- 22421324
TI  - Headspace concentrations of explosive vapors in containers designed for canine
      testing and training: theory, experiment, and canine trials.
AB  - It is a common misconception that the amount of explosive is the chief
      contributor to the quantity of vapor that is available to trained canines. In
      fact, this quantity (known as odor availability) depends not only on the amount
      of explosive material, but also the container volume, explosive vapor pressure
      and temperature. In order to better understand odor availability, headspace
      experiments were conducted and the results were compared to theory. The vapor
      phase concentrations of three liquid explosives (nitromethane, nitroethane and
      nitropropane) were predicted using the Ideal Gas Law for containers of various
      volumes that are in use for canine testing. These predictions were verified
      through experiments that varied the amount of sample, the container size, and the
      temperature. These results demonstrated that the amount of sample that is needed
      to saturate different sized containers is small, predictable and agrees well with
      theory. In general, and as expected, once the headspace of a container is
      saturated, any subsequent increase in sample volume will not result in the
      release of more vapors. The ability of canines to recognize and alert to
      differing amounts of nitromethane has also been studied. In particular, it was
      found that the response of trained canines is independent of the amount of
      nitromethane present, provided it is a sufficient quantity to saturate the
      container in which it is held.

PMID- 22421325
TI  - Intrapulmonary aquaporin-5 expression as a possible biomarker for discriminating
      smothering and choking from sudden cardiac death: a pilot study.
AB  - The diagnosis of mechanical asphyxia as a cause of death, especially smothering
      and choking lacking evident injury, is one of the most difficult tasks in
      forensic pathology. The present study investigated the intrapulmonary expressions
      of aquaporins (AQPs; AQP-1 and AQP-5), as markers of water homeostasis, in
      forensic autopsy cases (total n=64, within 48 h postmortem) of mechanical
      asphyxiation due to neck compression (strangulation, n=24), including
      manual/ligature strangulation (n=12) and atypical hanging (n=12), smothering
      (n=7) and choking (n=8), compared with sudden cardiac death (n=14) and acute
      brain injury (n=11). Quantification of mRNA using a Taqman real-time PCR assay
      system demonstrated suppressed expression of AQP-5, but not AQP-1, in smothering
      and choking, compared with that in strangulation as well as sudden cardiac death
      and acute brain injury death. Immunostaining of AQP-5 was weakly detected in a
      linear pattern in the type I alveolar epithelial cells in smothering and choking
      cases, while cardiac and brain injury death showed marked positivity, and most
      strangulation cases had AQP-5-positive granular aggregates and fragments in intra
      alveolar spaces. These observations indicate a partial difference in pulmonary
      molecular pathology among these causes of death, suggesting a procedure for
      possible discrimination of smothering and choking from sudden cardiac death.

PMID- 22421326
TI  - Is the length of the sternum reliable for estimating adult stature? A pilot study
      using fresh sterna and a test of two methods using dry sterna.
AB  - Stature estimation is one of the four attributes of the biological profile
      obtained from human skeletal remains. The length of the long bones has been
      consistently used to estimate stature from regression equations, but these may be
      useless when dealing with fresh or decomposed mutilated remains. Until recently,
      there was no consistent assessment of the reliability of measurements of the
      sternum for stature estimation. The purpose of this paper is to test previously
      developed regression formulae for stature based on measurements of the dry
      sternum and to assess the reliability of measurements of the fresh sternum in
      estimating stature. The formulae developed by Menezes et al. and Singh et al.
      were applied to a sample of 5 known stature skeletons from the identified human
      skeletal collection curated at the National Museum of Natural History, in Lisbon,
      Portugal. Testing of these formulae showed that estimated stature confidence
      intervals do not allow discrimination between individuals with similar stature.
      The length of the fresh sternum was measured on a sample of 45 male individuals
      autopsied at the National Institute of Legal Medicine - North Delegation (Porto,
      Portugal). Cadaver length was regressed on sternum length and a simple linear
      regression formula was obtained. The regression model provided a 95% confidence
      interval of 13.32 cm and a correlation coefficient of only 0.329. Compared to
      other studies, regression formulae based on the length of the sternum provided
      considerably larger standard errors than that based on long bone lengths. These
      results suggest that the length of the sternum has limited forensic value and
      relatively low reliability in estimating stature from mutilated human skeletal
      remains, either skeletonized or fresh.

PMID- 22421327
TI  - Nosocomial outbreak of Klebsiella pneumoniae harbouring bla(KPC-3) in France
      subsequent to a patient transfer from Italy.

PMID- 22421328
TI  - Sensitivities of ciprofloxacin-resistant Mycobacterium tuberculosis clinical
      isolates to fluoroquinolones: role of mutant DNA gyrase subunits in drug
      resistance.
AB  - Minimum inhibitory concentrations of sitafloxacin, gatifloxacin, moxifloxacin,
      sparfloxacin, levofloxacin and ciprofloxacin against 59 ciprofloxacin-resistant
      clinical isolates of Mycobacterium tuberculosis from Japan were determined. The
      isolates were most susceptible to sitafloxacin and gatifloxacin. To understand
      better the basis for drug resistance, nucleotide sequences encoding the gyrA and
      gyrB quinolone resistance-determining region were determined. Predicted amino
      acid sequences revealed distinct mutational patterns likely to be responsible for
      fluoroquinolone resistance. Double gyrA mutations as well as mutations in both
      gyrA and gyrB correlated with increased resistance to all fluoroquinolones.

PMID- 22421329
TI  - Emergence of resistance to antibacterial agents: the role of quaternary ammonium
      compounds--a critical review.
AB  - Quaternary ammonium compounds (QACs) are widely distributed in hospitals,
      industry and cosmetics. Little attention has been focused on the potential impact
      of QACs on the emergence of antibiotic resistance in patients and the
      environment. To assess this issue, we conducted a literature review on QAC
      chemical structure, fields of application, mechanism of action, susceptibility
      testing, prevalence, and co- or cross-resistance to antibiotics. Special
      attention was paid to the effects of QACs on microflora; in particular, the issue
      of the potential of QACs for applying selective pressure on multiple-antibiotic
      resistant organisms was raised. It was found that there is a lack of standardised
      procedures for interpreting susceptibility test results. QACs have different
      impacts on the minimum inhibitory concentrations of antibacterials depending on
      the antibacterial compound investigated, the resistance genes involved, the
      measuring methodology and the interpretative criteria. The unmet needs for
      adequate detection of reduced susceptibility to QACs and antibiotics include (i)
      a consensus definition for resistance, (ii) epidemiological cut-off values and
      (iii) clinical resistance breakpoints. This review advocates the design of
      international guidelines for QAC use.

PMID- 22421330
TI  - Effects of sub-minimum inhibitory concentrations of antimicrobial agents on
      Streptococcus mutans biofilm formation.
AB  - Many studies have demonstrated that sub-minimum inhibitory concentrations (sub
      MICs) of antimicrobial agents can inhibit bacterial biofilm formation. However,
      the mechanisms by which antimicrobial agents at sub-MICs inhibit biofilm
      formation remain unclear. At present, most studies are focused on Gram-negative
      bacteria; however, the effects of sub-MICs of antimicrobial agents on Gram
      positive bacteria may be more complex. Streptococcus mutans is a major cariogenic
      bacterium. In this study, the S. mutans growth curve as well as the expression of
      genes related to S. mutans biofilm formation were evaluated following treatment
      with 0.5* MIC of chlorhexidine (CHX), tea polyphenols and sodium fluoride (NaF),
      which are common anticaries agents. The BioFlux system was employed to generate a
      biofilm under a controlled flow. Morphological changes of the S. mutans biofilm
      were observed and analysed using field emission scanning electron microscopy and
      confocal laser scanning microscopy. The results indicated that these three common
      anticaries agents could significantly upregulate expression of the genes related
      to S. mutans biofilm formation, and S. mutans exhibited a dense biofilm with an
      extensive extracellular matrix following treatment with sub-MICs of NaF and CHX.
      These findings suggest that sub-MICs of anticaries agents favour S. mutans
      biofilm formation, which might encourage dental caries progression.

PMID- 22421331
TI  - Prevalence of multidrug-resistant Acinetobacter baumannii producing OXA-23-like
      from a healthcare facility of Gangwon Province, South Korea.

PMID- 22421332
TI  - Double-input compartmental modeling and spectral analysis for the quantification
      of positron emission tomography data in oncology.
AB  - In positron emission tomography (PET) studies involving organs different from the
      brain, ignoring the metabolite contribution to the tissue time-activity curves
      (TAC), as in the standard single-input (SI) models, may compromise the accuracy
      of the estimated parameters. We employed here double-input (DI) compartmental
      modeling (CM), previously used for [11C]thymidine, and a novel DI spectral
      analysis (SA) approach on the tracers 5-[18F]fluorouracil (5-[18F]FU) and
      [18F]fluorothymidine ([18F]FLT). CM and SA were performed initially with a SI
      approach using the parent plasma TAC as an input function. These methods were
      then employed using a DI approach with the metabolite plasma TAC as an additional
      input function. Regions of interest (ROIs) corresponding to healthy liver,
      kidneys and liver metastases for 5-[18F]FU and to tumor, vertebra and liver for
      [18F]FLT were analyzed. For 5-[18F]FU, the improvement of the fit quality with
      the DI approaches was remarkable; in CM, the Akaike information criterion (AIC)
      always selected the DI over the SI model. Volume of distribution estimates
      obtained with DI CM and DI SA were in excellent agreement, for both parent 5
      [18F]FU (R(2) = 0.91) and metabolite [18F]FBAL (R(2) = 0.99). For [18F]FLT, the
      DI methods provided notable improvements but less substantial than for 5-[18F]FU
      due to the lower rate of metabolism of [18F]FLT. On the basis of the AIC values,
      agreement between [18F]FLT K(i) estimated with the SI and DI models was good (R2
      = 0.75) for the ROIs where the metabolite contribution was negligible, indicating
      that the additional input did not bias the parent tracer only-related estimates.
      When the AIC suggested a substantial contribution of the metabolite [18F]FLT
      glucuronide, on the other hand, the change in the parent tracer only-related
      parameters was significant (R2 = 0.33 for K(i)). Our results indicated that
      improvements of DI over SI approaches can range from moderate to substantial and
      are more significant for tracers with a high rate of metabolism. Furthermore,
      they showed that SA is suitable for DI modeling and can be used effectively in
      the analysis of PET data.

PMID- 22421333
TI  - Foreword to the special issue on AFM in biology & bionanomedicine.
AB  - It is now more than twenty-five years since the initial description of scanning
      probe microscopy and almost twenty years since the first commercial microscopes
      found their way into research labs. Currently, we are at a very interesting
      juncture, during which atomic force microscopy (AFM) is moving from basic
      research to successful applications in analytical biology and diagnostic
      medicine. Thus, the timing of this special issue on "Atomic Force Microscopy in
      Biology & Bionanomedicine", documenting this transition in AFM usage, could not
      be more appropriate; particularly given the increasing importance of AFM as new
      or improved methods, reagents, and instrumentation are developed to address
      outstanding biological questions.

PMID- 22421334
TI  - Compliance profile of the human cornea as measured by atomic force microscopy.
AB  - The ability to accurately determine the elastic modulus of each layer of the
      human cornea is a crucial step in the design of better corneal prosthetics. In
      addition, knowledge of the elastic modulus will allow design of substrates with
      relevant mechanical properties for in vitro investigations of cellular behavior.
      Previously, we have reported elastic modulus values for the anterior basement
      membrane and Descemet's membrane of the human cornea, the surfaces in contact
      with the epithelial and endothelial cells, respectively. We have completed the
      compliance profile of the stromal elements of the human cornea by obtaining
      elastic modulus values for Bowman's layer and the anterior stroma. Atomic force
      microscopy (AFM) was used to determine the elastic modulus, which is a measure of
      the tissue stiffness and is inversely proportional to the compliance. The elastic
      response of the tissue allows analysis with the Hertz equation, a model that
      provides a relationship between the indentation force and depth and is a function
      of the tip radius and the modulus of the substrate. The elastic modulus values
      for each layer of the cornea are: 7.5+/-4.2 kPa (anterior basement membrane),
      109.8+/-13.2 kPa (Bowman's layer), 33.1+/-6.1 kPa (anterior stroma), and 50+/
      17.8 kPa (Descemet's membrane). These results indicate that the biophysical
      properties, including elastic modulus, of each layer of the human cornea are
      unique and may play a role in the maintenance of homeostasis as well as in the
      response to therapeutic agents and disease states. The data will also inform the
      design and fabrication of improved corneal prosthetics.

PMID- 22421335
TI  - Ovarian ultrastructure in virgin queens of Apis mellifera L. narcotized by CO2.
AB  - Ovaries of newly emerged virgin queens, aged 1, 3, 5, and 10 days, were submitted
      to an atmosphere of CO2 for 1 min, and studied by transmission electron
      microscopy. Newly emerged control and experimental queens were kept caged during
      15 days with six nurse workers (changed every 2 days) and fed with sugar candy
      and water ad libitum. For the ultrastructural studies, the ovaries were collected
      when the queens were 3, 5, 10, and 15 days old. The effect of the treatment on
      the ovary was mainly evaluated by cell death incidence and acid phosphatase
      detection. Neither the confinement nor CO2 treatment interfered with the pattern
      of queen ovarian development for up to 5 days; that is, no differences were
      observed in ovarian ultrastructure or acid phosphatase activity between control
      and treated queens. Beyond the age of 10 days, treated queens showed a lower rate
      of cell death than controls, but the positivity to acid phosphatase reaction
      remained similar in both. The protective effect of CO2 on cells, however, did not
      persist, and 15-day-old treated queens showed no differences compared to the
      controls in the rates of cell death or enzyme reactivity. In conclusion,
      treatment with CO2 did not significantly change the ultrastructure of ovarian
      cells, or acid phosphatase activity in them, during the caging time of the
      queens. From an applied perspective, the short-term imprisonment of newly emerged
      queens outside of the colony, as is done by beekeepers, does not seem to affect
      their performance in terms of future fertility, although the narcosis, as applied
      in this study, may negatively affect their long-term performance.

PMID- 22421338
TI  - The interleukin-6 pathway and atherosclerosis.

PMID- 22421341
TI  - Green chemistry approaches to leather tanning process for making chrome-free
      leather by unnatural amino acids.
AB  - In the present study, green and sustainable method or eco-friendly approaches to
      tanning process based on unnatural D-amino acids (D-AA)-aldehyde (Ald) as a
      substitute for chrome-free tanning has been attempted. The distribution of
      optically active D-AA in tanned leather, the hydrothermal stability, the
      mechanical properties and resistance to collagenolytic activity of tanned
      leather, the evaluation of eco-friendly characteristics were investigated.
      Scanning electron microscopic (SEM) and Atomic force microscopic (AFM) analyses
      indicate the surface morphology and roughness, respectively, of the tanned
      leather collagen matrix. Shrinkage and Differential scanning calorimetric (DSC)
      analyses shows that the shrinkage temperature (T(s)) and denaturation temperature
      (T(d)) of tanned leather are related to the content of D-AA+Ald present in the
      leather matrix. It has been found that the T(s) of D-AA tanned leather is more
      than that of Ald tanned leather and also more or less equal to chrome tanned
      leather. Environmental impact assessment (EIA) shows that the developed process
      results in significant reduction in total solids content (TSC) and improves
      better biodegradability of organic compound present in the effluent compared to
      chrome tanning.

PMID- 22421342
TI  - A continuous pilot-scale system using coal-mine drainage sludge to treat acid
      mine drainage contaminated with high concentrations of Pb, Zn, and other heavy
      metals.
AB  - A series of pilot-scale tests were conducted with a continuous system composed of
      a stirring tank reactor, settling tank, and sand filter. In order to treat acidic
      drainage from a Pb-Zn mine containing high levels of heavy metals, the potential
      use of coal-mine drainage sludge (CMDS) was examined. The pilot-scale tests
      showed that CMDS could effectively neutralize the acidic drainage due to its high
      alkalinity production. A previous study revealed that calcite and goethite
      contained in CMDS contributed to dissolutive coprecipitation and complexation
      with heavy metals. The continuous system not only has high removal efficiencies
      (97.2-99.8%), but also large total rate constants (K(total), 0.21-10.18h(-1)) for
      all heavy metals. More specifically, the pilot system has a much higher Zn(II)
      loading rate (45.3gm(-3)day(-1)) than other reference systems, such as aerobic
      wetland coupled with algal mats and anoxic limestone drains. The optimum
      conditions were found to be a CMDS loading of 280gL(-1) and a flow rate of 8Lday(
      1), and the necessary quantity of CMDS was 91.3gL(-1)day(-1), as the replacement
      cycle of CMDS was determined to be 70 days.

PMID- 22421343
TI  - Degradation of Acid Orange 7 in aqueous solution by a novel
      electro/Fe2+/peroxydisulfate process.
AB  - A novel process in which electrochemistry (EC) was coupled with ferrous ion
      activation of peroxydisulfate (Fe(2+)/S(2)O(8)(2-)) was proposed for the
      decolorization of Acid Orange 7. In this process, the reaction between
      peroxydisulfate and externally added ferrous ion results in the production of
      sulfate free radical as well as ferric ion, and at the same time ferrous ion
      could be electro-regenerated at the cathode by the reduction of ferric ion. Color
      removal by the Fe(2+)/S(2)O(8)(2-) process was significantly enhanced in the
      presence of applied current. The effects of some important reaction parameters
      such as initial pH, current density, S(2)O(8)(2-) concentration and Fe(2+)
      concentration on the decolorization of Acid Orange 7 by EC/Fe(2+)/S(2)O(8)(2-)
      process were investigated. The results showed that the decolorization efficiency
      was not significantly affected by the initial pH value, and the decolorization
      efficiency increased with the increase of S(2)O(8)(2-) concentration and Fe(2+)
      concentration. The current densities had little effect on the decolorization of
      Acid Orange 7 at the beginning of the reaction, while it improved the
      decolorization efficiency after 60min reaction. The GC-MS analysis was employed
      to identify the intermediate products and a plausible degradation pathway is
      proposed. The chemical oxygen demand (COD) removal efficiency was 57.6% after
      60min reaction and it reached 90.2% when the reaction time was extended to
      600min. Toxicity test with Daphnia magna showed that the acute toxicity of the
      solution increased during the first stage of the reaction, and then gradually
      decreased with the progress of the oxidation.

PMID- 22421344
TI  - Mercury in coastal watersheds along the Chinese Northern Bohai and Yellow Seas.
AB  - The concentration of total mercury [Hg] in waters, sediments and biota (carp and
      crabs) as well as the concentration of methyl mercury [MeHg] in biota from
      upstream (surface water systems) and downstream (coastal and estuarine systems)
      areas within coastal watersheds along the Chinese Northern Bohai and Yellow Seas
      were investigated. In most waters tested, the [Hg] could have adverse effects on
      coastal wildlife. Based on the Chinese water quality standards for mercury, 67%
      of upstream waters cannot be used for agriculture or recreation. Furthermore, 53%
      of downstream waters cannot be used as harbors or for industrial development. The
      [Hg] in 3% of sediments from the Wuli and Luanhe Rivers were sufficient to cause
      adverse effects on ecosystems. The [Hg] in 41% of downstream crabs and the [MeHg]
      in 29% of downstream crabs were higher than the limits for human consumption set
      by the Chinese government. In all abiotic and biotic samples, only the downstream
      carp from the Northern Yellow Sea had a [Hg] or [MeHg] higher than those from the
      Northern Bohai Sea. Industrialization and urbanization were the primary sources
      of mercury contamination in the aquatic ecosystems studied.

PMID- 22421340
TI  - The interleukin-6 receptor as a target for prevention of coronary heart disease:
      a mendelian randomisation analysis.
AB  - BACKGROUND: A high circulating concentration of interleukin 6 is associated with
      increased risk of coronary heart disease. Blockade of the interleukin-6 receptor
      (IL6R) with a monoclonal antibody (tocilizumab) licensed for treatment of
      rheumatoid arthritis reduces systemic and articular inflammation. However,
      whether IL6R blockade also reduces risk of coronary heart disease is unknown.
      METHODS: Applying the mendelian randomisation principle, we used single
      nucleotide polymorphisms (SNPs) in the gene IL6R to evaluate the likely efficacy
      and safety of IL6R inhibition for primary prevention of coronary heart disease.
      We compared genetic findings with the effects of tocilizumab reported in
      randomised trials in patients with rheumatoid arthritis. FINDINGS: In 40 studies
      including up to 133,449 individuals, an IL6R SNP (rs7529229) marking a non
      synonymous IL6R variant (rs8192284; p.Asp358Ala) was associated with increased
      circulating log interleukin-6 concentration (increase per allele 9.45%, 95% CI
      8.34-10.57) as well as reduced C-reactive protein (decrease per allele 8.35%, 95%
      CI 7.31-9.38) and fibrinogen concentrations (decrease per allele 0.85%, 95% CI
      0.60-1.10). This pattern of effects was consistent with IL6R blockade from
      infusions of tocilizumab (4-8 mg/kg every 4 weeks) in patients with rheumatoid
      arthritis studied in randomised trials. In 25,458 coronary heart disease cases
      and 100,740 controls, the IL6R rs7529229 SNP was associated with a decreased odds
      of coronary heart disease events (per allele odds ratio 0.95, 95% CI 0.93-0.97,
      p=1.53*10(-5)). INTERPRETATION: On the basis of genetic evidence in human beings,
      IL6R signalling seems to have a causal role in development of coronary heart
      disease. IL6R blockade could provide a novel therapeutic approach to prevention
      of coronary heart disease that warrants testing in suitably powered randomised
      trials. Genetic studies in populations could be used more widely to help to
      validate and prioritise novel drug targets or to repurpose existing agents and
      targets for new therapeutic uses. FUNDING: UK Medical Research Council; British
      Heart Foundation; Rosetrees Trust; US National Heart, Lung, and Blood Institute;
      Du Pont Pharma; Chest, Heart and Stroke Scotland; Wellcome Trust; Coronary
      Thrombosis Trust; Northwick Park Institute for Medical Research; UCLH/UCL
      Comprehensive Medical Research Centre; US National Institute on Aging; Academy of
      Finland; Netherlands Organisation for Health Research and Development; SANCO;
      Dutch Ministry of Public Health, Welfare and Sports; World Cancer Research Fund;
      Agentschap NL; European Commission; Swedish Heart-Lung Foundation; Swedish
      Research Council; Strategic Cardiovascular Programme of the Karolinska
      Institutet; Stockholm County Council; US National Institute of Neurological
      Disorders and Stroke; MedStar Health Research Institute; GlaxoSmithKline; Dutch
      Kidney Foundation; US National Institutes of Health; Netherlands Interuniversity
      Cardiology Institute of the Netherlands; Diabetes UK; European Union Seventh
      Framework Programme; National Institute for Healthy Ageing; Cancer Research UK;
      MacArthur Foundation.

PMID- 22421345
TI  - Metabolic versatility of Gram-positive microbial isolates from contaminated river
      sediments.
AB  - Gram-positive bacteria from river sediments affected by the proximity of a
      petrochemical industrial site were isolated and characterized with respect to
      their ability to degrade a wide range of aromatic compounds. In this study we
      identified metabolically diverse Gram-positive bacteria capable of growth on wide
      range aromatic compounds in the presence of heavy metals and with the ability to
      accumulate biopolymers. Thirty-four isolates that were able to use 9 or more
      common aromatic pollutants, such as benzene, biphenyl, naphthalene etc. as a sole
      source of carbon and energy included members of Bacillus, Arthrobacter,
      Rhodococcus, Gordonia, Streptomyces, and Staphylococcus genus. Rhodococcus sp.
      TN105, Gordonia sp. TN103 and Arthrobacter sp. TN221 were identified as novel
      strains. Nine isolates were able to grow in the presence of one or more metals
      (mercury, cadmium, nickel) at high concentration (100mM). Seven isolates could
      degrade 15 different aromatic compounds and could grow in the presence of one or
      more heavy metals. Two of these isolates were resistant to multiple antibiotics
      including erythromycin and nalidixic acid. One third of isolates could accumulate
      at least one biopolymer. Twelve isolates (mainly Bacillus sp. and Arthrobacter
      sp.) accumulated polyphosphate, 3 Bacillus sp. accumulated polyhydroxybutyrate,
      while 4 isolates could accumulate exopolysaccharides.

PMID- 22421347
TI  - The stabilization of Au NP-AChE nanocomposites by biosilica encapsulation for the
      development of a thiocholine biosensor.
AB  - We report on the construction of an amperometric biosensor based on the
      immobilization of the enzyme acetylcholinesterase (AChE) onto gold nanoparticles
      (Au NPs). The active enzyme is covalently bound directly onto the surface of the
      Au NPs via a thiol bond. This immobilization provides increased stability and
      high electron-transfer between the colloidal Au NPs, the catalyst and the
      transducer surface. To further increase the biosensor stability by protecting the
      enzyme from denaturation and protease attack, a layer of biosilica was grown
      around the Au NP enzyme nanocomposite. All steps, i.e., the conjugation of the
      enzyme to the gold nanoparticles and the encapsulation into biosilica, are
      monitored and confirmed by ATR-FT-IR spectroscopy. The stabilizing effect of the
      entrapment was evaluated amperometrically, while the operation of the biosensor
      was monitored over a period of 4 months. The initial sensitivity of the biosensor
      was calculated to be 27.58 nA mM(-1) with a linear response to the concentration
      of the substrate in the range from 0.04 to 0.4 mM. It is thus shown that the
      biosilica nanocomposites doped with Au NPs-AChE conjugates create a system that
      provides both signal mediation and significant enzyme stabilization over the
      existing AChE biosensor. The biosensor had retained all its activity at the end
      of the 4 months, compared with the normal AChE biosensor whose activity reached
      50% after only 42 days of operation.

PMID- 22421339
TI  - Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta
      analysis of 82 studies.
AB  - BACKGROUND: Persistent inflammation has been proposed to contribute to various
      stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor
      (IL6R) signalling propagates downstream inflammation cascades. To assess whether
      this pathway is causally relevant to coronary heart disease, we studied a
      functional genetic variant known to affect IL6R signalling. METHODS: In a
      collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation
      to a panel of conventional risk factors and inflammation biomarkers in 125,222
      participants. We also compared the frequency of Asp358Ala in 51,441 patients with
      coronary heart disease and in 136,226 controls. To gain insight into possible
      mechanisms, we assessed Asp358Ala in relation to localised gene expression and to
      postlipopolysaccharide stimulation of interleukin 6. FINDINGS: The minor allele
      frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid
      concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for
      association per minor allele >=0.04 for each). By contrast, for every copy of
      358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4
      38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C
      reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7
      1.3). For every copy of 358Ala inherited, risk of coronary heart disease was
      reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or
      interleukin-6 production in monocytes. INTERPRETATION: Large-scale human genetic
      and biomarker data are consistent with a causal association between IL6R-related
      pathways and coronary heart disease. FUNDING: British Heart Foundation; UK
      Medical Research Council; UK National Institute of Health Research, Cambridge
      Biomedical Research Centre; BUPA Foundation.

PMID- 22421348
TI  - Fabrication of a modified electrode based on Fe(3)O(4)NPs/MWCNT nanocomposite:
      application to simultaneous determination of guanine and adenine in DNA.
AB  - Multi-walled carbon nanotubes decorated with Fe(3)O(4) nanoparticles
      (Fe(3)O(4)NPs/MWCNT) were prepared and used to construct a novel biosensor for
      the simultaneous detection of adenine and guanine. The direct electro-oxidation
      of adenine and guanine on the modified electrode were investigated by linear
      sweep voltammetry. The results indicate a remarkable increase in the oxidation
      peak currents together with negative shift in the oxidation peak potentials for
      both adenine and guanine, in comparison to the bare glassy carbon electrode
      (GCE). The surface morphology and nature of the composite film deposited on GCE
      were characterized by transmission electron microscopy, atomic force microscopy,
      cyclic voltammetry and electrochemical impedance spectroscopy. The
      Fe(3)O(4)NPs/MWCNT based electrochemical biosensor exhibits linear ranges of 0.01
      10 MUM and 0.05-8 MUM with detection limits of 1 nM and 5 nM for adenine and
      guanine, respectively. The proposed method was successfully applied for a highly
      sensitive simultaneous determination of trace amounts of adenine and guanine in
      DNA of fish sperm samples with satisfactory results. The experimental detection
      limit was found to be equal to 3 ng mL(-1) DNA. The value of (G+C)/(A+T) in DNA
      was calculated to be 0.81. The fabricated electrode showed excellent
      reproducibility, repeatability and stability.

PMID- 22421346
TI  - A novel library screen identifies immunosuppressors that promote osteoblast
      differentiation.
AB  - Bone homeostasis can be compromised by an increase in osteoclast-mediated
      resorption and/or a decrease in osteoblast-mediated bone deposition. While many
      efforts have focused on treating osteoclast resorption, there has been less
      emphasis on identifying strategies for promoting osteoblast function. Herein, we
      describe a high-throughput screening assay to select for small molecules that
      augment bone morphogenetic protein-2 (BMP-2)-mediated osteoblast lineage
      commitment. After an initial screen of 5405 compounds; consisting of FDA-approved
      drugs, known bioactives, and compounds with novel chemical makeup, we identified
      45 small molecules that promoted osteoblast commitment. Of the 45 candidates,
      there was a broad array of classes that included nine retinoid
      analogs/derivatives and four immunosuppressants, notably rapamycin and FK-506,
      which were chosen for further study. Treatment of osteoblast precursor cells with
      rapamycin or FK-506, either alone, or synergistically with BMP-2, increased
      levels of phospho-Smad 1/5/8 protein and transcription of Runx-2, Osx and Smad-7,
      consistent with a role in promoting osteoblast differentiation. Only FK-506 was
      able to enhance osteocalcin transcripts and Alizarin Red staining, both late
      markers for differentiation. When osteoblast differentiation was suppressed with
      exogenous TGF-beta1 treatment, rapamycin (but not FK-506) was able to rescue
      expression of differentiation markers, indicating distinct but overlapping
      activity of these compounds. Collectively, these data add to an understanding of
      pathways engaged in osteoblastogenesis, support a role for non-redundant
      immunosuppressant signaling, and provide a novel approach for the discovery of
      potentially therapeutic compounds that affect bone remodeling.

PMID- 22421349
TI  - Histopathology of peripapillary choroidal neovascularization.
AB  - The different therapeutic responses observed among choroidal neovascularization
      (CNV) of different etiologies, ages, and locations might be related to the
      presence of varied mediators. Two surgically removed peripapillary CNVs from two
      different patients were analyzed. One of the patients had received one
      intravitreous injection of bevacizumab 3 months earlier. CNV was analyzed using
      conventional histology and immunohistochemistry. Histological analysis showed
      intense neovascularization and epithelial and glial components. Vascular
      endothelial growth factor (VEGF) receptors were found in the endothelial cells
      and the epithelial cells of the CNV. VEGF was expressed in the patient who had
      not been previously treated with anti-VEGF. The CNV was deeply infiltrated by
      glial cells and invaded by microglial cells in one case. VEGF and VEGF receptors
      may be expressed, suggesting that therapies aiming at VEGF may be efficient only
      for a subtype of CNV and at a certain time point of their evolution.

PMID- 22421350
TI  - Vitreous cortex splitting in cases of vitreomacular traction syndrome.
AB  - The authors report four cases of vitreomacular traction syndrome with splitting
      of the posterior vitreous cortex. Spectral-domain optical coherence tomography
      (SD-OCT) was performed consecutively in 35 patients with vitreomacular traction
      syndrome between June 2007 and February 2011. SD-OCT showed perifoveal posterior
      vitreous detachment with splitting of the posterior vitreous cortex in 4 of 35
      eyes (at the fovea in 1 eye and the perifovea in 3 eyes). The separated cortex of
      the posterior lamella adhered to the retina in all 4 eyes. The posterior vitreous
      cortex may split at the macular area in cases of vitreomacular traction syndrome.

PMID- 22421351
TI  - SD-OCT patterns of the different stages of choroidal metastases.
AB  - A diagnosis of choroidal metastasis is based on the patient's clinical history,
      the tumor's ophthalmoscopic appearance, and instrumental imaging results such as
      ultrasonography, fluorescein angiography, fundus autofluorescence, indocyanine
      green angiography, and optical coherence tomography. Spectral-domain optical
      coherence tomography (SD-OCT) has provided additional useful information for
      clinical diagnosis: a pattern of hyperintense irregular spots in the context of
      the photoreceptor layer and in the retinal pigment epithelium, subretinal fluid,
      and marked irregularity of the retinal pigment epithelium with thickening and
      gross undulation. The authors describe a case of bilateral choroidal metastasis
      presenting peculiar SD-OCT features acquired at different stages. They emphasize
      the central role of SD-OCT among instrumental imaging procedures and for final
      successful diagnosis.

PMID- 22421352
TI  - The role of autonomic testing in the differentiation of Parkinson's disease from
      multiple system atrophy.
AB  - Differentiation of idiopathic Parkinson's disease (PD) from multiple system
      atrophy (MSA) can be difficult. Methods devised to help distinguish the two
      disorders include standardized autonomic testing and cardiac imaging with iodine
      123 meta-iodobenzylguanidine myocardial scintigraphy. MSA patients had more
      severe adrenergic and overall autonomic dysfunction when compared to control and
      PD patients. Area of anhidrosis on thermoregulatory sweat test was greater in MSA
      (67.4+/-12.42, p<0.001) versus PD patients (area of anhidrosis, 1.7+/-2.96).
      Postganglionic cardiac sympathetic innervation (iodine-123 meta
      iodobenzylguanidine) expressed as heart to mediastinal ratio was significantly
      lower in Parkinson's disease patients (1.4+/-0.40, p=0.025) compared to controls
      (2.0+/-0.29), but not in multiple system atrophy (2.0+/-0.76). These findings
      indicate that autonomic dysfunction is generalized and predominantly
      preganglionic in multiple system atrophy, and postganglionic in Parkinson's
      disease. In our hands the thermoregulatory sweat test provides the best
      distinction between MSA and PD. However further confirmatory studies using larger
      patient numbers are required. Currently a combination of clinical judgment and
      autonomic testing is recommended to help differentiate MSA and PD.

PMID- 22421353
TI  - Slug contributes to cadherin switch and malignant progression in muscle-invasive
      bladder cancer development.
AB  - OBJECTIVES: The Snail family of zinc finger transcription factors (i.e., Snail
      and Slug) predicts the tumor recurrence in superficial bladder cancers, while
      their roles in the development of muscle-invasion, metastasis, and
      chemoresistance in muscle-invasive bladder cancers with poor prognosis have not
      been investigated. This study evaluates the clinical significance of Slug in
      aggressive bladder cancer. MATERIALS AND METHODS: A pair of sublines (i.e., T24-P
      and T24-L) from a unique orthotropic metastatic model of bladder cancer was
      firstly utilized to identify the potential precursors contributing to those
      aggressive phenotypes. The coexpression of Slug, E-cadherin, and N-cadherin in
      bladder cancer cell lines (i.e., 5637, RT4, 253 J, J82, and T24) and tissues was
      evaluated by reverse transcription-polymerase chain reaction (RT-PCR), Western
      blotting, and immunohistochemistry staining analysis. The function of Slug
      expression on E- to N-cadherin switch, cell invasion, and chemoresistance to
      proapoptotic treatment was validated by gain-in-function and knockdown strategy
      in vitro. RESULTS: Slug was identified as one of the novel targets contributed to
      the aggressive phenotypes of T24-L cells, which showed enhanced cell invasive,
      metastatic, and chemoresistant potentials in vitro and in vivo as previously
      described. Up-regulation of Slug was significantly correlated with a higher tumor
      stage and the E- to N-cadherin switch in bladder cancer cells and tissues,
      whereas ectopic expression of Slug in bladder cancer 5637 and RT-4 cell lines
      promoted epithelial-to-mesenchymal transition (EMT), increased cell invasiveness
      and chemoresistance. By contrast, knocking down Slug using siRNA in T24-L cell
      lines reversed these changes. CONCLUSIONS: Slug elevates in invasive or
      metastatic bladder cancer and plays a critical role in EMT via control of
      cadherin switch. Slug may be a potential marker or target for improving the
      diagnosis and treatment of muscle-invasive bladder cancers.

PMID- 22421354
TI  - Clear-cell differentiation and lymphatic invasion, but not the revised TNM
      classification, predict lymph node metastases in pT1 penile cancer: a
      clinicopathologic study of 76 patients from a low incidence area.
AB  - OBJECTIVE: Prediction of lymph node (LN) metastases in penile invasive cancer
      relies on clinical features and histologic characteristics of the primary tumor.
      Correct prediction, however, is difficult, as only 50% patients undergoing
      lymphadenectomies will have LN metastases. In 2009, the tumor, nodes, metastases
      (TNM) classification for staging of early penile cancers was revised. We tested
      the predictive accuracy of the revised TNM classification in a low incidence area
      for penile carcinoma. MATERIALS AND METHODS: The presence of LN metastases in 76
      men with pT1 penile cancers was correlated with the 2009 TNM subclassification,
      which is based on a combined evaluation of tumor grade and lymphatic invasion,
      but also with individual parameters, such as histologic grade, lymphatic
      invasion, perineural invasion, invasion depth, growth pattern and human papilloma
      virus (HPV) status. RESULTS: 76pT1 penile cancers were reclassified into 31pT1a
      squamous cell carcinomas (SCC) and 45pT1b (41 SCC; 4 clear-cell carcinomas);
      12/22 men (55%; 8 SCC, 4 clear-cell carcinomas) undergoing lymphadenectomy for
      enlarged inguinal lymph nodes had metastases, 54 patients without enlarged LN and
      lymphadenectomies had no LN metastases during follow-up of median 47 months.
      Statistically, clear cell differentiation of the primary carcinoma was highly
      associated with metastases (100% clear-cell carcinomas vs. 11% SCC) and poor
      survival (50% vs. 5.5%). Among conventional SCC, only lymphatic invasion showed a
      highly significant association with metastases with 100% specificity. The 2009
      TNM classification, tumor grade alone, perineural invasion, growth pattern,
      invasion depth or HPV status could not predict LN status. Lymphadenectomy for
      enlarged LN resulted in 100% sensitivity and 42% predictive probability for
      identifying metastases and a 16% false positive rate. Statistically, survival
      correlated significantly with clear-cell differentiation and with lymphatic
      invasion in both clear-cell carcinomas and conventional SCC. CONCLUSIONS: Penile
      clear-cell carcinomas are more aggressive cancers than SCC. Our observation
      suggests a benefit of a prophylactic lymphadenectomy for patients with clear-cell
      carcinomas. Among conventional SCC, only lymphatic invasion predicted LN
      metastases. Neither tumor grade alone nor perineural invasion, growth pattern,
      depth of invasion, and subgrouping according to the revised TNM classification
      correlated with metastases. Clinical evaluation of the LN status was superior to
      histologic risk stratification.

PMID- 22421356
TI  - Prevalence and predictors of healthcare utilization among older people (60+):
      focusing on ADL dependency and risk of depression.
AB  - The aim of this study was to investigate healthcare utilization patterns over a
      six-year period among older people (60+), classified as dependent/independent in
      Activities of Daily Living (ADL) and/or at/not at risk of depression and to
      identify healthcare utilization predictors. A sample (n=1402) comprising ten age
      cohorts aged between 60 and 96 years was drawn from the Swedish National study on
      Aging and Care (SNAC). Baseline data were collected between 2001 and 2003. Number
      and length of hospital stays were collected for six years after baseline year.
      Group differences and mean changes over time were investigated. Healthcare
      utilization predictors were explored using multiple linear regression analysis.
      The results revealed that 21-24% had at least one hospital stay in the six years
      after baseline, 29-37% among ADL dependent subjects and 24-33% among those at
      risk of depression. There was a significant increase of hospital stays in all
      groups over time. ADL-dependent subjects and those at risk of depression had
      significant more hospital stays, except for those at/not at risk of depression in
      years 2, 4 and 5. The healthcare utilization predictors 5-6 years after baseline
      were mainly age, previous healthcare utilization and various symptoms and, in 1-2
      and 3-4 years after baseline, age, various diagnostic groups and various physical
      variables. Thus healthcare utilization patterns seem to be similar for the
      different groups, but it is difficult to find universal predictors. This suggests
      that different variables should be considered, including both ADL and
      psychosocial variables, when trying to identify future healthcare users.

PMID- 22421355
TI  - Early B-cell factors 2 and 3 (EBF2/3) regulate early migration of Cajal-Retzius
      cells from the cortical hem.
AB  - Cajal-Retzius (CR) cells play a crucial role in the formation of the cerebral
      cortex, yet the molecules that control their development are largely unknown.
      Here, we show that Ebf transcription factors are expressed in forebrain
      signalling centres-the septum, cortical hem and the pallial-subpallial boundary
      known to generate CR cells. We identified Ebf2, through fate mapping studies, as
      a novel marker for cortical hem- and septum-derived CR cells. Loss of Ebf2 in
      vivo causes a transient decrease in CR cell numbers on the cortical surface due
      to a migratory defect in the cortical hem, and is accompanied by upregulation of
      Ebf3 in this and other forebrain territories that produce CR cells, without
      affecting proper cortical lamination. Accordingly, using in vitro preparations,
      we demonstrated that both Ebf2 and Ebf3, singly or together, control the
      migration of CR cells arising in the cortical hem. These findings provide
      evidence that Ebfs directly regulate CR cell development.

PMID- 22421357
TI  - Micro-analytical characterisation of radioactive heterogeneities in samples from
      Central Asian TENORM sites.
AB  - The present work focuses on the use of micro-analytical techniques to demonstrate
      the heterogeneous distribution of radionuclides and metals in soils collected at
      Former Soviet Union mining sites in Central Asia. Based on digital
      autoradiography, radionuclides were heterogeneously distributed in soil samples
      collected at the abandoned uranium mining sites Kurday, Kazakhstan, Kadji Sai,
      Kyrgyzstan and Taboshar, Tajikistan. Using electron microscopy interfaced with X
      ray microanalysis submicron - mm-sized radioactive particles and rock fragments
      with U, As, Se and toxic metals on the surfaces were identified in Kurday and
      Kadji Sai samples. Employing scanning and tomographic (3D) synchrotron radiation
      based micro-X-ray fluorescence (MU-SRXRF) and synchrotron radiation based micro-X
      ray diffraction (MU-SRXRD) allowed us to observe the inner structure of the
      particles without physical sectioning. The distribution of elements in virtual
      crosssections demonstrated that U and a series of toxic elements were rather
      heterogeneously distributed also within individual radioactive TENORM particles.
      Compared to archived data, U in Kadji Sai particles was present as uraninite
      (U4O9+y or UO2+x) or Na-zippeite ((Na4(UO2)6[(OH)10(SO4)3].4H2O), i.e. U minerals
      with very low solubility. The results suggested that TENORM particles can carry
      substantial amount of radioactivity, which can be subject to re-suspension,
      atmospheric transport and water transport. Thus, the potential radioecological
      and radioanalytical impact of radioactive particles at NORM and TENORM sites
      worldwide should be taken into account. The present work also demonstrates that
      radioecological studies should benefit from the use of advanced methods such as
      synchrotron radiation based techniques.

PMID- 22421359
TI  - Translation of the cell adhesion molecule ALCAM in axonal growth cones -
      regulation and functional importance.
AB  - ALCAM is a cell adhesion molecule that is present on extending axons and has been
      shown to be crucial for elongation and navigation of retinal ganglion cell (RGC)
      axons. In the present study, we show that ALCAM mRNA is present in axonal growth
      cones of RGCs in vivo and in vitro, and that translation of ALCAM occurs in RGC
      growth cones separated from their soma. This growth cone translation is regulated
      by the 3'-untranslated region (3'-UTR) of ALCAM and depends on the activity of
      the kinases ERK and TOR (target of rapamycin). We also investigated the impact of
      the growth cone translation of ALCAM on axonal functions. Growth cone translation
      of ALCAM is crucial for the enhanced elongation of axons extending in contact
      with ALCAM protein. The local translation of ALCAM in the growth cone is able to
      rapidly counterbalance experimentally induced ALCAM internalization, thereby
      contributing to the maintenance of constant ALCAM levels in the plasma membrane.
      Assays where RGC axons have the choice to grow on laminin or both ALCAM and
      laminin - as is the case in the developing retina - reveal that the axonal
      preference for ALCAM-containing lanes depends on translation of ALCAM in growth
      cones. Taken together, these results show for the first time that translation of
      a cell adhesion molecule in growth cones, as well as the impact of this local
      translation on the behavior of axon and growth cone.

PMID- 22421358
TI  - Oxidative-stress-induced nuclear to cytoplasmic relocalization is required for
      Not4-dependent cyclin C destruction.
AB  - The yeast cyclin-C-Cdk8p kinase complex represses the transcription of a subset
      of genes involved in the stress response. To relieve this repression, cyclin C is
      destroyed in cells exposed to H(2)O(2) by the 26S proteasome. This report
      identifies Not4p as the ubiquitin ligase mediating H(2)O(2)-induced cyclin C
      destruction. Not4p is required for H(2)O(2)-induced cyclin C destruction in vivo
      and polyubiquitylates cyclin C in vitro by utilizing Lys48, a ubiquitin linkage
      associated with directing substrates to the 26S proteasome. Before its
      degradation, cyclin C, but not Cdk8p, translocates from the nucleus to the
      cytoplasm. This translocation requires both the cell-wall-integrity MAPK module
      and phospholipase C, and these signaling pathways are also required for cyclin C
      destruction. In addition, blocking cytoplasmic translocation slows the mRNA
      induction kinetics of two stress response genes repressed by cyclin C. Finally, a
      cyclin C derivative restricted to the cytoplasm is still subject to Not4p
      dependent destruction, indicating that the degradation signal does not occur in
      the nucleus. These results identify a stress-induced proteolytic pathway
      regulating cyclin C that requires nuclear to cytoplasmic relocalization and Not4p
      mediated ubiquitylation.

PMID- 22421360
TI  - Syntaxin 1C, a soluble form of syntaxin, attenuates membrane recycling by
      destabilizing microtubules.
AB  - Syntaxin 1C (STX1C), produced by alternative splicing of the stx1A gene, is a
      soluble syntaxin lacking a SNARE domain and a transmembrane domain. It is unclear
      how soluble syntaxin can control intracellular membrane trafficking. We found
      that STX1C affected microtubule (MT) dynamics through its tubulin-binding domain
      (TBD) and regulated recycling of intracellular vesicles carrying glucose
      transporter-1 (GLUT1). We demonstrated that the amino acid sequence VRSK of the
      TBD was important for the interaction between STX1C and tubulin and that wild
      type STX1C (STX1C-WT), but not the TBD mutant, reduced the V(max) of glucose
      transport and GLUT1 translocation to the plasma membrane in FRSK cells. Moreover,
      by time-lapse analysis, we revealed that STX1C-WT suppressed MT stability and
      vesicle-transport motility in cells expressing GFP-alpha-tubulin, whereas TBD
      mutants had no effect. We also identified that GLUT1 was recycled in the 45
      minutes after endocytosis and that GLUT1 vesicles moved along with MTs. Finally,
      we showed, by a recycling assay and FCM analysis, that STX1C-WT delayed the
      recycling phase of GLUT1 to PM, without affecting the endocytotic process of
      GLUT1. These data indicate that STX1C delays the GLUT1 recycling phase by
      suppressing MT stability and vesicle-transport motility through its TBD,
      providing the first insight into how soluble syntaxin controls membrane
      trafficking.

PMID- 22421361
TI  - beta-Catenin-SOX2 signaling regulates the fate of developing airway epithelium.
AB  - Wnt-beta-catenin signaling regulates cell fate during organ development and
      postnatal tissue maintenance, but its contribution to specification of distinct
      lung epithelial lineages is still unclear. To address this question, we used a
      Cre recombinase (Cre)-LoxP approach to activate canonical Wnt signaling
      ectopically in developing lung endoderm. We found that persistent activation of
      canonical Wnt signaling within distal lung endoderm was permissive for normal
      development of alveolar epithelium, yet led to the loss of developing bronchiolar
      epithelium and ectasis of distal conducting airways. Activation of canonical Wnt
      led to ectopic expression of a lymphoid-enhancing factor and a T-cell factor (LEF
      and TCF, respectively) and absence of SRY (sex-determining region Y)-box 2 (SOX2)
      and tumor protein p63 (p63) expression in proximal derivatives. Conditional loss
      of SOX2 in airways phenocopied epithelial differentiation defects observed with
      ectopic activation of canonical Wnt. Our data suggest that Wnt negatively
      regulates a SOX2-dependent signaling program required for developmental
      progression of the bronchiolar lineage.

PMID- 22421362
TI  - Irradiation-induced protein inactivation reveals Golgi enzyme cycling to cell
      periphery.
AB  - Acute inhibition is a powerful technique to test proteins for direct roles and
      order their activities in a pathway, but as a general gene-based strategy, it is
      mostly unavailable in mammalian systems. As a consequence, the precise roles of
      proteins in membrane trafficking have been difficult to assess in vivo. Here we
      used a strategy based on a genetically encoded fluorescent protein that generates
      highly localized and damaging reactive oxygen species to rapidly inactivate exit
      from the endoplasmic reticulum (ER) during live-cell imaging and address the long
      standing question of whether the integrity of the Golgi complex depends on
      constant input from the ER. Light-induced blockade of ER exit immediately
      perturbed Golgi membranes, and surprisingly, revealed that cis-Golgi-resident
      proteins continuously cycle to peripheral ER-Golgi intermediate compartment
      (ERGIC) membranes and depend on ER exit for their return to the Golgi. These
      experiments demonstrate that ER exit and extensive cycling of cis-Golgi
      components to the cell periphery sustain the mammalian Golgi complex.

PMID- 22421363
TI  - Loss of alphaT-catenin alters the hybrid adhering junctions in the heart and
      leads to dilated cardiomyopathy and ventricular arrhythmia following acute
      ischemia.
AB  - It is generally accepted that the intercalated disc (ICD) required for mechano
      electrical coupling in the heart consists of three distinct junctional complexes:
      adherens junctions, desmosomes and gap junctions. However, recent morphological
      and molecular data indicate a mixing of adherens junctional and desmosomal
      components, resulting in a 'hybrid adhering junction' or 'area composita'. The
      alpha-catenin family member alphaT-catenin, part of the N-cadherin-catenin
      adhesion complex in the heart, is the only alpha-catenin that interacts with the
      desmosomal protein plakophilin-2 (PKP2). Thus, it has been postulated that alphaT
      catenin might serve as a molecular integrator of the two adhesion complexes in
      the area composita. To investigate the role of alphaT-catenin in the heart, gene
      targeting technology was used to delete the Ctnna3 gene, encoding alphaT-catenin,
      in the mouse. The alphaT-catenin-null mice are viable and fertile; however, the
      animals exhibit progressive cardiomyopathy. Adherens junctional and desmosomal
      proteins were unaffected by loss of alphaT-catenin, with the exception of the
      desmosomal protein PKP2. Immunogold labeling at the ICD demonstrated in the
      alphaT-catenin-null heart a preferential reduction of PKP2 at the area composita
      compared with the desmosome. Furthermore, gap junction protein Cx43 was reduced
      at the ICD, including its colocalization with N-cadherin. Gap junction remodeling
      in alphaT-catenin-knockout hearts was associated with an increased incidence of
      ventricular arrhythmias after acute ischemia. This novel animal model
      demonstrates for the first time how perturbation in alphaT-catenin can affect
      both PKP2 and Cx43 and thereby highlights the importance of understanding the
      crosstalk between the junctional proteins of the ICD and its implications for
      arrhythmogenic cardiomyopathy.

PMID- 22421364
TI  - Forced binding of the origin of replication complex to chromosomal sites in
      Drosophila S2 cells creates an origin of replication.
AB  - Origins of replication in higher eukaryotes appear to lack specific sequence
      characteristics and those mapped often appear to be spread over several
      kilobases. This has complicated the study of site-specific events at origins of
      replication in vivo. Here we show that fusion of a Gal4-binding domain to
      proteins of the origin of replication complex (Orc) is sufficient to direct
      initiation to Gal4-binding sites inserted in the Drosophila S2 cell chromosome.
      The activation appears to go via an authentic route, taking place only in the S
      phase of the cell cycle and involving the formation of a prereplication complex.
      We have also shown that the origin-associated acetylation of histone H4 at K12
      can be directed to the region of Orc binding by the presence of Orc. We expect
      that this system can provide a useful tool for the study of site-specific events
      at origins of replication in higher eukaryotes and a means to dissect Orc
      dependent and Orc-independent events at origins.

PMID- 22421365
TI  - Homotypic RANK signaling differentially regulates proliferation, motility and
      cell survival in osteosarcoma and mammary epithelial cells.
AB  - RANKL (receptor activator of NF-kappaB ligand) is a crucial cytokine for
      regulating diverse biological systems such as innate immunity, bone homeostasis
      and mammary gland differentiation, operating through activation of its cognate
      receptor RANK. In these normal physiological processes, RANKL signals through
      paracrine and/or heterotypic mechanisms where its expression and function is
      tightly controlled. Numerous pathologies involve RANKL deregulation, such as bone
      loss, inflammatory diseases and cancer, and aberrant RANK expression has been
      reported in bone cancer. Here, we investigated the significance of RANK in tumor
      cells with a particular emphasis on homotypic signaling. We selected RANK
      positive mouse osteosarcoma and RANK-negative preosteoblastic MC3T3-E1 cells and
      subjected them to loss- and gain-of-RANK function analyses. By examining a
      spectrum of tumorigenic properties, we demonstrate that RANK homotypic signaling
      has a negligible effect on cell proliferation, but promotes cell motility and
      anchorage-independent growth of osteosarcoma cells and preosteoblasts. By
      contrast, establishment of RANK signaling in non-tumorigenic mammary epithelial
      NMuMG cells promotes their proliferation and anchorage-independent growth, but
      not motility. Furthermore, RANK activation initiates multiple signaling pathways
      beyond its canonical target, NF-kappaB. Among these, biochemical inhibition
      reveals that Erk1/2 is dominant and crucial for the promotion of anchorage
      independent survival and invasion of osteoblastic cells, as well as the
      proliferation of mammary epithelial cells. Thus, RANK signaling functionally
      contributes to key tumorigenic properties through a cell-autonomous homotypic
      mechanism. These data also identify the likely inherent differences between
      epithelial and mesenchymal cell responsiveness to RANK activation.

PMID- 22421366
TI  - Scopolamine induced memory impairment; possible involvement of NMDA receptor
      mechanisms of dorsal hippocampus and/or septum.
AB  - BACKGROUND AND AIM: The anatomical connections of septum and hippocampus and the
      influence of cholinergic and glutamatergic projections in these sites have been
      reported. In the present study, the effect of pre-training intra-dorsal
      hippocampal (CA1) and intra-medial septal (MS) administration of scopolamine, a
      nonselective muscarinic acetylcholine antagonist, and NMDA receptor agents and
      their interactions, on acquisition of memory have been investigated. METHODS: The
      animals were bilaterally implanted with chronic cannulae in the CA1 regions and
      in the medial septum. Animals were trained in a step-through type inhibitory
      avoidance task, and tested 24h after training to measure step-through latency as
      memory retrieval. RESULTS: Intra-CA1 or intra-MS injections of scopolamine (0.5,
      1 and 2 MUg/rat) and D-AP7 (a competitive NMDA receptor antagonist; 0.025, 0.05
      and 0.1 MUg/rat) reduced, while NMDA (0.125 and 0.25 MUg/rat) increased memory.
      Intra-MS injection of a subthreshold dose of NMDA reduced scopolamine induced
      amnesia in the MS. However, similar injection of NMDA into CA1 did not alter
      scopolamine response when injected into CA1. Moreover, intra-MS or -CA1 injection
      of a subthreshold dose of NMDA did not alter scopolamine response in the CA1 or
      MS respectively. On the other hand, co-administration subthreshold doses of D-AP7
      and scopolamine into CA1 and/or MS induced amnesia. CONCLUSIONS: The cholinergic
      system between septum and CA1 are modulating memory acquisition processes induced
      by glutamatergic system in the CA1 or septum and co-activation of these systems
      in these sites can influence learning and memory.

PMID- 22421368
TI  - A dramatic fetal outcome following transplacental transfer of dasatinib.
AB  - Chronic myeloid leukemia is a chronic myeloproliferative disorder of
      hematopoietic stem cells that occurs in 10% of cases in women of childbearing
      age. Treatment is mainly based on tyrosine kinase inhibitors such as imatinib,
      dasatinib, or nilotinib. However, the maternal and embryofetal safety of these
      drugs in pregnant women is poorly documented. Here, we report the case of a 23
      year-old woman diagnosed with a chronic myeloid leukemia. She was treated with
      dasatinib while she was diagnosed as being pregnant at 7 weeks of gestation.
      Obstetric monitoring showed fetal hydrops associated with severe fetal
      bicytopenia, leading to termination of pregnancy at 16 weeks of gestation.
      Dasatinib concentrations were 4 ng/ml in maternal plasma (usual concentration), 3
      ng/ml in fetal plasma, and 2 ng/ml in amniotic fluid. Fetal karyotype was normal.
      To our knowledge, this is the first report clearly quantifying the amount of
      transplacental transfer of dasatinib. Moreover, fetal hematological toxicity
      (leukopenia and thrombocytopenia), edema, ascites, and pleural effusions
      described in this case report are well-known side effects of dasatinib in adults.
      Hence, this case highlights the imputability of dasatinib in this adverse
      outcome, and clearly questions its safety during pregnancy.

PMID- 22421367
TI  - Withdrawal from THC during adolescence: sex differences in locomotor activity and
      anxiety.
AB  - Research suggests that the use and abuse of marijuana can be especially harmful
      if it occurs during adolescence, a period of vast developmental changes
      throughout the brain. Due to the localization of cannabinoid receptors within the
      limbic system and the established effects of cannabinoids on emotional states and
      anxiety levels of rats and humans, we studied the sex- and dose-related effects
      of Delta9-tetrahydrocannabinol (THC, the main psychoactive component in
      marijuana) on behavior and anxiety during spontaneous withdrawal. Male and female
      Sprague Dawley rats were administered 2, 7.5 or 15 mg/kg THC or vehicle from
      postnatal day 35-41 (approximating mid-adolescence in humans). Locomotor activity
      and anxiety-related behaviors were measured during drug administration and
      abstinence. THC caused significant dose-dependent locomotor depression during
      drug administration. Locomotor depression initially abated upon drug cessation,
      but re-emerged by the end of the abstinence period and was greater in female than
      male rats. We found sensitization to the locomotor-depressing effects of THC in
      middle- and high-dose rats and the subsequent development of tolerance in high
      dose rats. The high dose of THC increased anxiety-like behaviors while the low
      dose decreased anxiety-like behaviors during drug administration, with females
      more sensitive to the anxiogenic effects of THC than males. During abstinence,
      females were again especially sensitive to the anxiogenic effects of THC. This
      study demonstrates sexually-dimorphic effects of THC on anxiety-related behaviors
      and locomotor activity during and after THC administration during adolescence.
      This information may be useful in the development of therapeutic approaches for
      the treatment of marijuana withdrawal in adolescents.

PMID- 22421369
TI  - Enhancement of the cytotoxic potential of the mixed EGFR and DNA-targeting 'combi
      molecule' ZRBA1 against human solid tumour cells by a bis-quinazoline-based drug
      design approach.
AB  - ZRBA1 is a quinazoline-based molecule termed 'combi-molecule' designed to block
      the epidermal growth factor receptor (EGFR) and further degrade to FD105, an EGFR
      inhibitor plus a DNA-alkylating agent. To augment the potency of ZRBA1, we
      designed JDE52, a bistriazene that, following degradation, was 'programmed' to
      yield higher concentrations of the free inhibitor FD105 and a more cytotoxic
      bifunctional DNA-damaging species. The results indicated that JDE52 was capable
      of inducing significant blockade of EGFR phosphorylation, DNA strand breaks and
      interstrand cross-links in human cells. The fluorescent property of FD105, the
      secondary inhibitor that both JDE52 and ZRBA1 are capable of releasing, has
      permitted the analysis of its levels in tumour cells by ultraviolet flow
      cytometry. It was found that JDE52 was indeed capable of significantly releasing
      higher levels of fluorescence (P<0.05) in human tumour cells when compared with
      ZRBA1. Apoptosis was triggered by JDE52 at a faster rate than ZRBA1 and led to
      higher levels of cell killing. The results in toto suggest that the superior
      potency of JDE52, when compared with ZRBA1, may be imputed to mechanisms
      associated with the generation of higher intracellular concentrations of FD105
      and to the induction of DNA cross-links. These combined mechanisms (blockade of
      EGFR-tyrosine kinase and induction of cross-links) contributed to an accelerated
      rate of apoptosis by JDE52. This study conclusively demonstrated that designing
      molecules as prodrugs of high levels of quinazoline inhibitors of EGFR and
      bifunctional DNA cross-linking species is a valid strategy to enhance the potency
      of mixed EGFR-DNA-targeting combi-molecules.

PMID- 22421370
TI  - Artesunate induces G0/G1 cell cycle arrest and iron-mediated mitochondrial
      apoptosis in A431 human epidermoid carcinoma cells.
AB  - The anticancer effects of artesunate (ART) have been well documented. However,
      its potential against skin cancer has not been explored yet. Herein we reported
      that 60 MUmol/l ART effectively inhibited A431 (human epidermoid carcinoma cells)
      growth but not that of HaCaT (normal human keratinocyte cells). Our results
      revealed that ART induced cell cycle arrest at G0/G1 phase through the
      downregulation of cyclin A1, cyclin B, cyclin D1, Cdk2, Cdk4, and Cdk6. This
      correlated with the upregulation of p21 and p27. The 5-bromodeoxyuridine
      incorporation assay also indicated that ART treatment reduced DNA synthesis in a
      time-dependent manner. Furthermore, ART induced mitochondrial apoptosis, as
      evidenced by annexin V/propidium iodide staining and western blot analysis.
      Interestingly, ART-induced apoptosis diminished under iron-deficient conditions
      but intensified under iron-overload conditions. Taken together, these findings
      demonstrated the potential of ART in treating skin cancer through the induction
      of G0/G1 cell cycle arrest and iron-mediated mitochondrial apoptosis and
      supported further investigations in other test systems.

PMID- 22421371
TI  - Does the hypopharyngeal cavernous body protect the development of Zenker's
      diverticulum?
AB  - OBJECTIVE: The aim of this study was to examine the morphology of the cavernous
      body at the pharyngoesophageal segment. METHODS: In 47 cadavers the submucosal
      vascular plexus of the pharyngoesophageal segment and the cricopharyngeal muscle
      were examined. RESULTS: A vascular plexus which was macroscopically non visible
      or slightly identified was observed in the majority of the specimens (28 or
      59.6%). Fourteen of the cadavers (29.8%) exhibited macroscopically lightly
      observable blood vessels which were covering a discontinuous area of the
      hypopharyngeal wall. In the other five specimens (10.6%) the vascular plexus was
      covering a large part of the dorsal wall of the pharyngoesophageal segment as a
      compact mass. The grade of dilation of the vascular plexus corresponded to the
      degree of protrusion of the cricopharyngeal muscle. CONCLUSIONS: In the case of a
      persistent constricted cricopharyngeal muscle, the dilation of the hypopharyngeal
      cavernous body may protect from developing a Zenker's diverticulum by reinforcing
      the Killian's dehiscence.

PMID- 22421372
TI  - C-type natriuretic peptide and its receptors in atherosclerotic plaques of the
      carotid artery of clinically asymptomatic patients.
AB  - OBJECTIVES: C-type natriuretic peptide (CNP) has anti-inflammatory, anti
      proliferative and anti-migratory properties. No data exist on the presence of CNP
      in human atherosclerotic plaques of the carotid artery. Therefore, this study
      aimed to analyse qualitatively the distribution pattern and characteristics of
      CNP and its receptors in both, early and advanced human carotid plaques, as well
      as in stable and unstable lesions. In addition, the aim of this study was to
      evaluate CNP and its receptors as possible biomarkers to predict plaque stability
      in advanced lesions. METHODS: Advanced carotid artery plaques of 40 asymptomatic
      patients (20 histologically stable and 20 histologically unstable) and early
      arteriosclerotic lesions of three patients were analysed. RESULTS: Serum level of
      CNP was similar in patients with stable and unstable plaques (196 +/- 19 pg ml(
      1) vs. 198 +/- 25 pg ml(-1), p = 0.948). Expression level of natriuretic peptide
      receptor 3 (NPR3) was significantly higher in unstable plaques compared to stable
      plaques (5.6 +/- 1.8% vs. 1.7 +/- 0.5%, p = 0.045). Expression levels of CNP and
      NPR2 were higher in unstable plaques but the differences were not statistically
      significant. The distribution pattern of CNP, NPR2 and NPR3 varied qualitatively
      between early and advanced carotid plaques. No relevant histological differences
      were observed with respect to plaque stability. CONCLUSIONS: This study shows the
      presence of CNP and its receptors in atherosclerotic plaques of human carotid
      artery, with increased expression of NPR3 in histologically unstable plaques. In
      this study, serum CNP was not associated with histological plaque stability. In
      future, larger studies are required to further evaluate whether proteins of the
      CNP axis would be useful as biomarkers.

PMID- 22421373
TI  - Porcine model of ruptured abdominal aortic aneurysm repair.
AB  - OBJECTIVES: To validate a porcine model of ruptured abdominal aortic aneurysm
      (rAAA) repair. DESIGN: Experimental study. METHODS: Ten experimental and five
      sham-operated pigs were studied. Instrumentation for cardiac output (CO)
      measurement, regional blood flow (renal-REN and portal-PORT) and blood sampling
      (inferior vena cava (IVC), renal and portal vein) was done. Microcirculation was
      visualised sublingually and in ileostoma. PROTOCOL: simulation of rAAA with
      bleeding (mean arterial pressure (MAP) 45 mmHg) and increased abdominal pressure
      (25 mmHg) for 4 h; 2 h of infrarenal clamp with shed blood retransfusion; 11 h of
      post-surgery care. RESULTS: Six experimental pigs completed the protocol and are
      presented. Bleeding decreased CO to 95%, PORT to 80% and REN to 10% of baseline.
      From clamping on CO and PORT increased above baseline whereas REN (47%) with
      creatinine clearance remained compromised till the end. Microcirculation was
      affected more in ileum than sublingually. Approximately threefold increase in
      cytokines (tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL
      10) and oxidative stress markers (thiobarbituric acid-reactive substances (TBARs)
      and 4-hydroxy-2-trans-nonenal (HNE) was observed. Only mild increase in IL-6 and
      TBARs was observed in sham-operated animals. Organ histology did not reveal
      differences between groups. CONCLUSIONS: This near-lethal model of rAAA induced
      expected severe deterioration of haemodynamics and metabolism accompanied with a
      moderate inflammatory and oxidative stress response.

PMID- 22421374
TI  - Thermal ablation in the management of superficial thrombophlebitis.
AB  - INTRODUCTION: In superficial thrombophlebitis (ST), saphenous high ligation and
      stripping may be indicated. Endovenous thermal ablation (ETA) was hitherto not
      reported for ST management. We treated three ST patients using ETA and describe
      one in more detail. REPORT: An 81 year-old man with ST at the medial lower leg
      and a refluxing GSV underwent ETA of the GSV. Since thrombi were present, the GSV
      was punctured at the inguinal crease and the laser catheter introduced caudad in
      order to prevent embolism. DISCUSSION: In ST, ETA might prevent thrombus
      expansion and embolism. However, this approach requires further optimisation and
      scrutiny.

PMID- 22421375
TI  - Commentary on 'Treatment of aortic arch aneurysms with a modular transfemoral
      multibranched stent-graft: initial experience'.

PMID- 22421376
TI  - Rifampicin-soaked silver polyester versus expanded polytetrafluoro-ethylene
      grafts for in situ replacement of infected grafts in a porcine randomised
      controlled trial.
AB  - BACKGROUND: To compare the efficacy of in situ replacement with rifampicin-soaked
      silver-coated polyester (RSSCP) to that of expanded polytetrafluoroethylene
      (ePTFE) graft replacements in a porcine model for early aortic prosthetic
      vascular graft infection (PVGI). MATERIAL AND METHODS: Sixty pigs received
      polyester or silver-coated grafts with an 8 mm diameter implanted end-to-end in
      the infrarenal aorta, and the grafts were inoculated with approximately
      10(6)Staphylococcus aureus. All developed S. aureus PVGI. Two weeks later, the 52
      surviving pigs were randomised to undergo in situ graft replacement with ePTFE or
      RSSCP grafts followed by oral administration of 300 mg rifampicin and 750 mg
      ciprofloxacin twice a day, postoperatively. After three weeks, all pigs were
      sacrificed. In situ perigraft swabs and graft material were analysed for S.
      aureus quantitatively. RESULTS: Only one out of 25 RSSCP grafts were infected
      with S. aureus, whereas 15 of 27 ePTFE grafts were infected after 3 weeks (OR =
      0.022, 95% CI: 0.002, 0.219, P = 0.001). CONCLUSIONS: In situ replacement with
      RSSCP grafts and oral rifampicin plus ciprofloxacin is more efficiency in
      eradicating S. aureus PVGI than ePTFE grafts treated with same oral antibiotics
      in a porcine aortic PVGI model.

PMID- 22421378
TI  - Hibiscus vitifolius (Linn.) root extracts shows potent protective action against
      anti-tubercular drug induced hepatotoxicity.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Hibiscus vitifolius Linn.
      (Malvaceae) is used for the treatment of jaundice in the folklore system of
      medicine in India. This study is an attempt to evaluate the hepatoprotective
      activity of the roots of Hibiscus vitifolius against anti-tubercular drug induced
      hepatotoxicity. MATERIALS AND METHODS: Hepatotoxicity was induced in albino rats
      of either sex by oral administration of a combination of three anti-tubercular
      drugs. Petroleum ether, chloroform, methanol and aqueous extracts of roots of
      Hibiscus vitifolius (400mg/kg/day) were evaluated for their possible
      hepatoprotective potential. RESULTS: All the extracts were found to be safe up to
      a dose of 2000mg/kg. Among the four extracts studied, oral administration of
      methanol extract of Hibiscus vitifolius at 400mg/kg showed significant difference
      in all the parameters when compared to control. There was a significant (P<0.001)
      reduction in the levels of serum aspartate amino transaminase, alanine amino
      transferase, alkaline phosphatase, lactate dehydrogenase, total and direct
      bilirubin, where as an increase was found in the levels of total cholesterol,
      total protein and albumin. Liver homogenate studies showed a significant increase
      in the levels of total protein, phospholipids and glycogen, and a reduction in
      the levels of total lipids, triglycerides, and cholesterol against control
      animals. In the tissue anti-oxidant studies, we found a significant increase in
      the levels of catalase and superoxide dismutase, whereas there was marked
      reduction in the levels of thiobarbituric acid reactive substances, as compared
      to control. Histology of liver sections of the animals treated with the extracts
      showed significant reduction of necrosis and fatty formation when compared with
      control specimens. CONCLUSION: These findings suggest that the root extracts of
      Hibiscus vitifolius have potent hepatoprotective activity, thereby justifying its
      ethnopharmacological claim.

PMID- 22421379
TI  - Botany, traditional uses, phytochemistry and pharmacology of Apocynum venetum L.
      (Luobuma): A review.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Apocynum venetum L. (Apocynaceae, Luobuma ) has a
      long history as a Chinese traditional medicine with uses to calm the liver,
      soothe the nerves, dissipate heat, and promote diuresis. Recently, Luobuma tea
      has been commercialized as a sedative and anti-aging supplement that has become
      increasingly popular in North American and East Asian health food markets. AIMS
      OF THE REVIEW: The aim of this review is to provide an up-to-date and
      comprehensive overview of the botany, chemical constituents, traditional uses,
      pharmacological activities and safety aspects of Apocynum venetum in order to
      assess its ethnopharmacological use and to explore its therapeutic potentials and
      future opportunities for research. BACKGROUND AND METHODS: The accessible
      literature on Apocynum venetum written in English, Chinese and Japanese were
      collected and analyzed. The literatures included ancient Chinese herbal classics,
      pharmacopoeias and articles that included in Pubmed, Web of Science, Google
      Scholar and Wanfang. KEY FINDINGS: Modern pharmacological studies demonstrated
      that Apocynum venetum possess wide pharmacological activities that include
      antihypertensive, cardiotonic, hepatoprotective, antioxidant, lipid-lowering,
      antidepressant and anxiolytic effects, which can be explained by the presence of
      various flavonoid compounds in this plant. The traditional (Lop Nor region) use
      of Apocynum venetum with tobacco as an agent to detoxify nicotine may receive
      interest as a possible therapeutic option to detoxify the body from smoking.
      Based on animal studies and clinical trials, Apocynum venetum causes no severe
      side effects, even in a stable daily dosage (50mg/person/day) for more than three
      years. CONCLUSIONS: Apocynum venetum potentially has therapeutic potential in the
      prevention and treatment for the cardiovascular and neurological diseases,
      especially for high blood pressure, high cholesterol, neurasthenia, depression
      and anxiety. Further investigations are needed to explore individual bioactive
      compounds responsible for these in vitro and in vivo pharmacological effects and
      the mode of actions. Further safety assessments and clinical trials should be
      performed before it can be integrated into medicinal practices.

PMID- 22421380
TI  - Multiple scattering effects in Doppler optical coherence tomography of flowing
      blood.
AB  - We investigate the effect of multiple scattering on the optical coherence
      tomography (OCT) signal and the Doppler OCT signal of flowing blood. Doppler OCT
      measurements at 1300 nm are performed on flowing diluted porcine blood with
      hematocrit ranging between 0% and 15%. Measured blood hematocrit and mean red
      blood cell volume are used to calculate, using the discrete dipole approximation
      model, the (single) scattering coefficient and scattering anisotropy of blood.
      Monte Carlo simulations, based on the calculated scattering coefficients and
      scattering anisotropies, are compared to Doppler OCT measurements for hematocrit
      smaller than 10%. Good quantitative agreement between Doppler OCT measurements
      and Monte Carlo simulations is observed. Our measurements, calculations and
      simulations explain the relatively low attenuation coefficients and well
      preserved flow profiles measured with Doppler OCT for flowing blood. Monte Carlo
      simulations demonstrate the effect of the scattering anisotropy of the medium on
      the strength of multiple scattering effects in Doppler OCT signals. With
      increasing scattering anisotropy the OCT attenuation decreases; the distortion of
      the flow profile is strongest at intermediate scattering anisotropies (~0.6).

PMID- 22421381
TI  - Phenotypic grouping of 141 BmNPVs lacking viral gene sequences.
AB  - We constructed a series of gene knockout BmNPVs (KOVs) for each of 141 genes
      (Gomi et al., 1999; Katsuma et al., 2011) using the BmNPV T3 bacmid system (Ono
      et al., 2007) and lambda red recombination system (Datsenko and Wanner, 2000). In
      a subsequent analysis of the properties needed for infection using a marker gene,
      egfp (enhanced green fluorescent protein gene), inserted into the polyhedrin
      locus, the knockout viruses (KOVs) were subdivided into four phenotypic types, A
      to D. Type-A (86 KOVs) showed the ability to expand infections equivalent to the
      control while type-B (8 KOVs) spread infections more slowly. Type-C (37 KOVs)
      expressed egfp in transfected-BmN cells but the production of infectious viruses
      was not observed. Type-D (10 KOVs) showed no ability to express egfp even in the
      transfection experiments. KOVs lacking genes (pkip (Bm15), gp41 (Bm66), bro-d
      (Bm131), Bm20, 48, 65, 91, 93, or 101) previously identified as being essential,
      were placed in the viable type-A and B categories.

PMID- 22421382
TI  - Structural insights into the classification of Mud Crab Reovirus.
AB  - Cryo-electron microscopy was applied to analyze mud crab reovirus (MCRV), which
      causes 'sleeping disease' in mud crab, Scylla serrata, a marine species cultured
      in China. We present here the three dimensional structure of MCRV at 13.8A
      resolution. The outer capsid shell is composed of 260 trimers with complete T=13
      icosahedral symmetry. A major difference between MCRV and previously reported
      aquareoviruses is that it lacks a pentameric turret structure. These results
      together with recently published molecular biological evidence (Deng et al.,
      2012) indicate that, from a structural perspective, MCRV should be classified as
      a new member of the family Reoviridae.

PMID- 22421384
TI  - Diabetes remission after bariatric surgery: which are the mechanisms?

PMID- 22421385
TI  - Neural correlates of autobiographical memory in amnestic Mild Cognitive
      Impairment.
AB  - Episodic memory dysfunction, commonly assessed with word list recall, is the main
      characteristic of amnestic Mild Cognitive Impairment (aMCI). While brain
      pathology underlying this kind of memory impairment is well established in aMCI,
      little is known about the effect of neurodegeneration on autobiographical memory.
      The present study investigated neuronal correlates of autobiographical memory in
      aMCI patients (n=12) and healthy elderly controls (n=13) using functional
      magnetic resonance imaging (fMRI). Additionally, voxel-based morphometry (VBM)
      was employed to reveal brain pathology in aMCI patients. Neuropsychological
      assessment showed significant impairment in episodic memory tasks (immediate and
      delayed word list recall) in aMCI patients. Moreover, VBM revealed significantly
      reduced gray matter concentration, which was most pronounced in the temporal
      lobes of aMCI patients. Despite episodic memory impairment and atrophy in areas
      that are associated with encoding and recall of episodic memories, aMCI patients
      showed no alterations in brain activation associated with autobiographical memory
      retrieval. These findings could suggest that autobiographical memory is subserved
      by a different neuronal network than episodic memory and that the two memory
      systems are differently affected by aMCI.

PMID- 22421386
TI  - Prenatally engineered autologous amniotic fluid stem cell-based heart valves in
      the fetal circulation.
AB  - Prenatal heart valve interventions aiming at the early and systematic correction
      of congenital cardiac malformations represent a promising treatment option in
      maternal-fetal care. However, definite fetal valve replacements require growing
      implants adaptive to fetal and postnatal development. The presented study
      investigates the fetal implantation of prenatally engineered living autologous
      cell-based heart valves. Autologous amniotic fluid cells (AFCs) were isolated
      from pregnant sheep between 122 and 128 days of gestation via transuterine
      sonographic sampling. Stented trileaflet heart valves were fabricated from
      biodegradable PGA-P4HB composite matrices (n = 9) and seeded with AFCs in vitro.
      Within the same intervention, tissue engineered heart valves (TEHVs) and unseeded
      controls were implanted orthotopically into the pulmonary position using an in
      utero closed-heart hybrid approach. The transapical valve deployments were
      successful in all animals with acute survival of 77.8% of fetuses. TEHV in-vivo
      functionality was assessed using echocardiography as well as angiography. Fetuses
      were harvested up to 1 week after implantation representing a birth-relevant
      gestational age. TEHVs showed in vivo functionality with intact valvular
      integrity and absence of thrombus formation. The presented approach may serve as
      an experimental basis for future human prenatal cardiac interventions using fully
      biodegradable autologous cell-based living materials.

PMID- 22421387
TI  - Use of the VennerTM A.P. AdvanceTM video laryngoscope for biopsy examination of
      the base of the tongue.
AB  - Biopsy specimens taken from the base of the tongue can be non-diagnostic, because
      of errors in sampling and tissue samples that are too small or superficial. The
      VennerTM A.P. AdvanceTM video laryngoscope (Intavent Direct, Maidenhead, UK) is
      an anaesthetic laryngoscope designed for use in patients with a difficult airway.
      We present a pilot study that compares video laryngoscope-assisted biopsy
      examination of the base of the tongue with the standard technique using a
      surgical laryngoscope. The video laryngoscope gives a wide view of the base of
      the tongue and the ability to use sinus biopsy forceps, which can take larger and
      deeper specimens.

PMID- 22421388
TI  - Perineural invasion in malignant melanoma.

PMID- 22421389
TI  - Intraoral external oblique ridge compared with transbuccal lateral cortical plate
      fixation for the treatment of fractures of the mandibular angle: prospective
      randomised trial.
AB  - Since the initial description by Michelet et al. and research by Champy et al.
      the placement of a single, four-hole, monocortical, osteosynthesis plate has been
      considered an acceptable method of fixation for a fracture of the mandibular
      angle. We investigated the null hypothesis that there is no difference in the
      incidence of postoperative removal of an infected plate between miniplates placed
      on the mandibular external oblique ridge and those placed on the buccal surface
      of the mandible through a transbuccal approach to treat a fracture of the angle
      of the mandible. Patients were randomised to having their angle fractures treated
      with a ridge plate placed intraorally or transbucally. Other variables were
      investigated including the effect of smoking, drinking alcohol, oral hygiene, and
      the method of holding the reduction on removal of the plate, occlusal outcome,
      and degree of preoperative anatomical displacement and postoperative reduction.
      We also studied the operating time required for the two techniques, the effect of
      the presence and consequent removal of a wisdom tooth in the line of the
      fracture, and the effect of delay in taking the patient to theatre for subsequent
      removal of the plate for infection. Of the 261 angle fractures 34 (13%) plates
      were removed because of infection, and 6 of these (18%) required a further period
      of fixation, such as intermaxillary fixation, to treat non-union. The transbuccal
      plate had a significantly lower postoperative infection rate (6/124, 5%) than the
      ridge plate (28/137, 20%) (p=0.001). Smoking adversely affected the healing of
      angle fractures (p=0.000). Displacement of fractures is related to the infection
      rate (p=0.003), and there are no significant relations between delay in going to
      theatre or the presence and potential removal of a wisdom tooth in the line of
      the fracture and infection rate. There was a highly significant difference
      between the rate of removal of plates placed intraorally on the external oblique
      ridge, and plates placed transbucally (p=0.000). Transbuccal plates were far less
      likely to need removal for infection than ridge plates, odds ratio 5.05.

PMID- 22421390
TI  - Single surgical step for endoscopic surgery and orbital reconstruction of a
      silent sinus syndrome.
AB  - Silent sinus syndrome (SSS) is an uncommon disease characterised by enophthalmos,
      caused by ipsilateral maxillary sinus atelectasis. The diagnosis is clinical with
      radiological confirmation. The treatment has two objectives: to regulate the
      aeration of the maxillary sinus through achieving normal nasal cavity drainage
      and to restore the orbital architecture. A case of SSS treated in our hospital in
      a single surgical intervention is reported. 

PMID- 22421391
TI  - Radiation-induced leiomyosarcoma of the posterior neck region.
AB  - INTRODUCTION: Leiomyosarcomas are mesenchymal malignant tumours that appear in
      smooth muscle cells. Their most frequent locations are the uterus and
      gastrointestinal tract. Their occurrence in head and neck is considered
      exceptional. We present a patient with a posterior neck region leiomyosarcoma who
      had received radiation for a nasopharyngeal carcinoma 20 years earlier. The
      incidence ratio of these tumours in radiated patients (therefore considered
      radiation-induced) ranges from 0,035 to 0,2%. Radiation-induced sarcomas are
      difficult to diagnose due to the induration and fibrosis in the radiated area and
      the non-specific symptoms that they present. Their prognosis is very poor.

PMID- 22421392
TI  - Maturational changes in the human envelope-following responses.
AB  - INTRODUCTION: The auditory ability to discriminate rapid changes in the envelope
      of language sounds is essential for speech comprehension. Human envelope
      following responses (EFRs) are useful for objective measurement of temporal
      auditory processing in subjects who are unable to give accurate behavioural
      responses (e.g., young children). OBJECTIVE: To evaluate age-dependent changes in
      EFRs during the first 2 years of life. METHODS: The EFRs were recorded in a
      sample of 16 well babies distributed into 2 age groups (G1: 12 newborns; G2: 4
      babies of 2 years). The EFRs were evoked by white noise carrier stimuli with a
      sweep of modulation frequencies from 20 to 200 Hz presented at 50 dB HL. RESULTS:
      The age-related changes affected both morphology and EFR detectability. The main
      morphological differences were at the expense of frequencies below 50 Hz, where
      the first component P1 was not well defined in either of the 2 age groups. For
      all modulation frequencies, age significantly affected EFR amplitude and
      detectability. CONCLUSIONS: The present study provides the first evidence on EFR
      maturation. Some understanding of normal EFR development would facilitate a
      better use of this technique in clinically-objective measurement of auditory
      temporal processing in infants who cannot provide reliable behavioural responses.

PMID- 22421393
TI  - Errorless academic compliance training: a school-based application for young
      students with autism.
AB  - Errorless academic compliance training is a graduated, noncoercive approach to
      treating oppositional behavior in children. In the present study, three teaching
      staff in a special education classroom were trained to conduct this intervention
      with three male students diagnosed with autism spectrum disorders. During
      baseline, staff delivered a range of academic and other classroom requests and
      recorded student compliance. A hierarchy of compliance probabilities was then
      calculated, ranging from Level 1 (requests yielding high levels of compliance) to
      Level 4 (those typically yielding noncompliance). At treatment initiation,
      teaching staff delivered high densities of Level 1 requests and provided
      reinforcement for compliance. Subsequent request levels were faded in over time,
      at a slow enough rate to ensure continued high compliance. By intervention end,
      all three students demonstrated substantially improved compliance to classroom
      requests that had commonly yielded noncompliance before intervention. Covariant
      improvement in on-task skills was also evident.

PMID- 22421394
TI  - Correction of the TRUE summations in volume sources.
AB  - The correction factors for volume sources may be approximated using average
      efficiencies determined by experiment or by Monte Carlo methods in the same way
      as for point sources. This simple technique does not take into account properly
      the absorption of photons in the source, nor the change of the effective solid
      angle. A more precise method must take into account for the spatial distribution
      of products of efficiencies eta(peak)*eta(total) (for summing-out) or
      eta(peak)*eta(peak) (for summing-in) over the volume of the source. The
      differences between the approximate and the more precise method are discussed.

PMID- 22421395
TI  - Standardization of Ga-68 by coincidence measurements, liquid scintillation
      counting and 4pigamma counting.
AB  - The radionuclide (68)Ga is one of the few positron emitters that can be prepared
      in-house without the use of a cyclotron. It disintegrates to the ground state of
      (68)Zn partially by positron emission (89.1%) with a maximum energy of 1899.1
      keV, and partially by electron capture (10.9%). This nuclide has been
      standardized in the frame of a cooperation project between the Radionuclide
      Metrology laboratories from CIEMAT (Spain) and CNEA (Argentina). Measurements
      involved several techniques: 4pibeta-gamma coincidences, integral gamma counting
      and Liquid Scintillation Counting using the triple to double coincidence ratio
      and the CIEMAT/NIST methods. Given the short half-life of the radionuclide
      assayed, a direct comparison between results from both laboratories was excluded
      and a comparison of experimental efficiencies of similar NaI detectors was used
      instead.

PMID- 22421396
TI  - Measurements of 64Cu and 68Ga half-lives and gamma-ray emission intensities.
AB  - The (64)Cu and (68)Ga half-lives and gamma-ray intensities were measured at IFIN
      HH. The determination of absolute photon emission intensities was based on
      absolute activity standardizations carried out in this laboratory using the 4piPC
      gamma coincidence method. The half-lives were measured with a well-type
      ionization chamber. The photon emission intensities (relative and absolute
      values) were measured with a calibrated high-resolution gamma-ray spectrometer.
      The results obtained and their uncertainties are discussed and compared with
      values of other authors.

PMID- 22421397
TI  - A low noise preamplifier with optoelectronic overload protection for
      radioactivity measurement.
AB  - Pulses from detectors used for radioactivity measurement can vary in size by
      several orders of magnitude. Large pulses will lead to saturation at the
      preamplifier output and extension of the pulse length. As a consequence, the dead
      time of the system increases and pulses may be lost. Electronic design techniques
      employed to protect against overloading tend to increase the amplifier noise
      level. However, an optoelectronic method of overload protection has been devised
      which has only a negligible effect on noise. An infrared light emitting diode
      interfaced to the output of the preamplifier is linked by fibre optic cable to an
      ultra-low leakage photodiode at the input. The conduction of the photodiode
      increases with the amplitude of the preamplifier output signal. Excess current is
      thereby prevented from entering the preamplifier and causing saturation. The
      preamplifier has been tested on 4pi beta-gamma and gas counting systems and found
      to give good protection against overloading.

PMID- 22421398
TI  - Calibration of KRISS reference ionization chamber for key comparison of (99m)Tc
      measurement.
AB  - KRISS, as the national metrology institute of Korea, has used a reference
      ionization chamber system to certify the activity of (99m)Tc aqueous sources, but
      could only recently participate in a comparison exercise by the BIPM (BIPM.RI(II)
      K4.Tc-99m) to secure the international equivalence of (99m)Tc radioactivity
      measurement by way of the BIPM transfer instrument (SIRTI). The KRISS ionization
      chamber system was calibrated about 100 days before the comparison with a (99m)Tc
      solution source standardized by the 4pibeta(LS)-gamma(NaI(Tl)) coincidence
      counting method. During the comparison, beginning with a higher activity mother
      solution, the KRISS ionization chamber measured its specific activity without a
      dilution. The activity of a diluted-solution source was measured by the SIRTI at
      the same time.

PMID- 22421399
TI  - A new measurement of the half-life of (166m)Ho.
AB  - The work presented here is a new and precise measurement of the half-life of
      (166m)Ho by determining the activity concentration, using an ionisation chamber
      calibrated for this nuclide, and measuring the number of (166m)Ho atoms using
      multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). Since
      the isotope (166)Er interferes with the mass spectrometric measurement, Er has to
      be eliminated from the (166m)Ho radioactive solution. The elimination was
      achieved using ion-exchange chromatography with the cation exchange resin Dowex
      AG 50W-X8 and 2-Hydroxybutanoic acid as the mobile phase. After a first transit
      through the chromatographic column, the purified (166m)Ho eluate was spiked with
      natural Er to get a resulting Er isotopic composition close to that of natural Er
      at better than 99.5%, and then it underwent two further separations to eliminate
      the Er. The activity concentration of this Er-free radioactive (166m)Ho solution
      was measured in our reference ionisation chamber calibrated for this nuclide by
      means of the 4pibeta(PC)-gamma and 4pibeta(PS)-4pigamma coincidence techniques
      and integral counting with a well-type NaI(Tl) detector and Monte Carlo
      efficiencies. An aliquot of this standardized solution was sent to the Paul
      Scherrer Institute (PSI) for mass concentration determination using an isotope
      dilution MC-ICP-MS approach. The mass concentration of (166m)Ho in this solution
      was determined with 0.25% relative standard uncertainty. This value was
      corroborated by two other independent measurements. The new half-life of
      (166m)Ho, 1132.6(39) years (k=1), is compatible with the value determined in
      1965, but is 5.6% shorter and about 43 times more precise.

PMID- 22421400
TI  - Acid and stretch, but not capsaicin, are effective stimuli for ATP release in the
      porcine bladder mucosa: Are ASIC and TRPV1 receptors involved?
AB  - Stretch-evoked ATP release from the bladder mucosa is a key event in signaling
      bladder fullness. Our aim was to examine whether acid and capsaicin can also
      release ATP and to determine the receptors involved, using agonists and
      antagonists at TRPV1 and acid-sensing ion channels (ASICs). Strips of porcine
      bladder mucosa were exposed to acid, capsaicin or stretch. Strip tension was
      monitored. Bath fluid was collected for ATP measurement. Gene expression of ASICs
      and TRPV1 in porcine bladders was quantified using quantitative real-time PCR
      (qRT-PCR). Stretch stimulus (150% of original length) repeatedly and
      significantly increased ATP release to approximately 45 times basal release. Acid
      (pH 6.5, 6.0, 5.6) contracted mucosal strips and also increased ATP release up to
      30-fold, without evidence of desensitization. Amiloride (0.3 MUM) reduced the
      acid-evoked ATP release by approximately 70%, while capsazepine (10 MUM) reduced
      acid-evoked ATP release at pH 6.0 and pH 5.6 (by 68% and 61%, respectively).
      Capsaicin (0.1-10 MUM) was ineffective in causing ATP release, and also failed to
      contract porcine mucosal or detrusor strips. Gene expression for ASIC1, ASIC2,
      ASIC3 and TRPV1 was seen in the lateral wall, dome, trigone and neck of both
      detrusor and mucosa. In conclusion, stretch and acid induce ATP release in the
      porcine bladder mucosa, but capsaicin is ineffective. The pig bladder is a well
      known model for the human bladder, however these data suggest that it should be
      used with caution, particularly for TRPV1 related studies.

PMID- 22421401
TI  - Protective effect of 20-hydroxyeicosatetraenoic acid (20-HETE) on adriamycin
      induced toxicity of human renal tubular epithelial cell (HK-2).
AB  - 20-Hydroxyeicosatetraenoic acid is a cytochrome P4504A11 metabolite of
      arachidonic acid that plays an important role in the regulation of human renal
      functions. In the present study, we investigated the role of 20
      hydroxyeicosatetraenoic acid on adriamycin induced toxicity in human renal
      tubular epithelial cells. Results showed that cell viability was decreased
      significantly and lactate dehydrogenase activity was increased significantly in a
      concentration-dependent manner when human renal tubular epithelial cells were
      incubated with adriamycin (10-7-10-3 mol/l) for 24h. In contrast, 20
      hydroxyeicosatetraenoic acid (0.1, 1, 10, 50 MUmol/l) increased cell survival and
      decreased lactate dehydrogenase activity concentration dependently in human renal
      tubular epithelial cells. When 20-hydroxyeicosatetraenoic acid (10, 50 MUmol/l)
      was co-administered with adriamycin (10-3 mol/l), it significantly increased cell
      viability and decreased lactate dehydrogenase activity. On the other hand, N
      hydroxy-N'-(4-butyl-2-methylphenyl)formamidine (HET-0016) (1 MUM), a selective
      inhibitor of 20-hydroxyeicosatetraenoic acid synthesizing enzyme exaggerated cell
      viability reduction and lactate dehydrogenase activity augmentation induced by
      adriamycin. Adriamycin suppressed the expression of cytochrome P4504A11 gene and
      its protein production in human renal tubular epithelial cells. Furthermore,
      adriamycin was more effective than N-hydroxy-N'-(4-butyl-2
      methylphenyl)formamidine at lowering the expression of cytochrome P4504A11 gene
      and its protein. These results suggest that 20-hydroxyeicosatetraenoic acid may
      protect adriamycin-induced toxicity of human renal tubular epithelial cells,
      meanwhile, adriamycin-induced toxicity of human renal tubular epithelial cells
      possibly involves inhibiting cytochrome P4504A11 expression.

PMID- 22421402
TI  - Congenital heart surgeon's technical proficiency affects neonatal hospital
      survival.
AB  - OBJECTIVE: Risk factors for mortality after neonatal cardiac surgery have been
      seldom studied. We sought to identify contemporary risk factors for mortality and
      the impact of surgical technical performance on surgical outcomes after neonatal
      cardiac surgery. METHODS: We conducted a matched case-control study comparing 56
      neonates who died after cardiac surgery (2002-2008) with 56 survivors matched by
      surgical procedure and year of surgery. Surgical efficacy for repair or
      palliation was graded using a reliable simple surgical technical score. Patient
      and surgical characteristics were compared for the survivors and nonsurvivors
      using paired analyses. RESULTS: There was no significant difference between
      patients who died and their matched controls in terms of age, Aristotle score,
      Risk Adjustment in Congenital Heart Surgery-1 category, and single versus
      biventricular repair. When compared with survivors, patients who died were more
      likely to be premature (41% vs 5%, P < .001), to weigh less than 2.5 kg (25% vs
      9%, P = .05), and to have inadequate surgical repair or palliation (55% vs 9%, P
      < .001). Cardiopulmonary bypass time was longer for the patients who died
      (median, 159 vs 133 minutes, P = .002). Highest postoperative lactate (median,
      9.0 vs 6.0, P < .001), use of extracorporeal membrane oxygenation (71% vs 13%, P
      < .001), and reoperation during the same admission (75% vs 2%, P < .001) were
      also associated with death. In multivariable analysis, inadequate surgical repair
      or palliation (odds ratio, 11, P = .02) and need for postoperative extracorporeal
      membrane oxygenation (odds ratio, 5.1, P = .009) were the only risk factors
      associated with hospital death. CONCLUSIONS: Our study highlights the need for
      optimal technical performance to minimize neonatal deaths. This has important
      implications when sustaining or developing a pediatric cardiac program.

PMID- 22421403
TI  - Performance evaluation of a pediatric viscous impeller pump for Fontan
      cavopulmonary assist.
AB  - OBJECTIVE: The anatomic and physiologic constraints for pediatric cavopulmonary
      assist differ markedly from adult Fontan circulations owing to smaller vessel
      sizes and risk of elevated pulmonary resistance. In this study, hemodynamic and
      hemolysis performance of a catheter-based viscous impeller pump (VIP) to power
      the Fontan circulation is assessed at a pediatric scale (~15 kg) and performance
      range (0-30 mm Hg). METHODS: Computer simulation and mock circulation studies
      were conducted to assess the hydraulic performance, acute hemodynamic response to
      different levels VIP support, and the potential for vena caval collapse.
      Computational fluid dynamics simulations were used to estimate VIP hydraulic
      performance, shear rates, and potential for hemolysis. Hemolysis was quantified
      in a mock loop with fresh bovine blood. RESULTS: A VIP augmented 4-way total
      cavopulmonary connection flow at pediatric scales and restored systemic pressures
      and flows to biventricular values, without causing flow obstruction or suction.
      VIP generated flows up to 4.1 L/min and pressure heads of up to 38 mm Hg at
      11,000 rpm. Maximal shear rate was 160 Pa, predicting low hemolysis risk.
      Observed hemolysis was low with plasma free hemoglobin of 11.4 mg . dL(-1) . h(
      1). CONCLUSIONS: A VIP will augment Fontan cavopulmonary flow in the proper
      pressure and flow ranges, with low hemolysis risk under more stringent pediatric
      scale and physiology compared with adult scale. This technology may be developed
      to simultaneously reduce systemic venous pressure and improve cardiac output
      after stage 2 or 3 Fontan repair. It may serve to compress surgical staging,
      lessening the pathophysiologic burden of repair.

PMID- 22421404
TI  - A new method to fenestrate the Fontan circulation.

PMID- 22421405
TI  - Baicalin is anti-inflammatory in cigarette smoke-induced inflammatory models in
      vivo and in vitro: A possible role for HDAC2 activity.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease
      characterized by airway obstruction and progressive lung inflammation, which is
      insensitive to corticosteroids therapies. In this study, we investigated the
      mechanism underlying the attenuation of cigarette smoke (CS)-induced respiratory
      inflammation by baicalin, a flavonoid compound isolated from the root of
      Scutellaria baicalensis Georgi, in vivo and in vitro. In vivo, mice were exposed
      to smoke of 15 cigarettes for 1 h/day, 6 days/week for 3 months and dosed with
      baicalin (25, 50 and 100mg/kg) or dexamethasone (1mg/kg). In vitro, A549 cells
      were incubated with baicalin (10, 50 and 100 MUM) or dexamethasone (10(-12), 10(
      10), 10(-8) and 10(-6)M) followed by treatments with cigarette smoke extract
      (CSE, 2.5 and 5%), or TNF-alpha (10 ng/ml), or trichostatin A (TSA, 100 ng/ml).
      We found that baicalin significantly protected pulmonary function and attenuated
      CS-induced inflammatory response by decreasing inflammatory cells and production
      of TNF-alpha, IL-8 and MMP-9. This result was not found in the group treated with
      dexamethasone. Baicalin also showed efficacy in enhancing histone deacetylase
      (HDAC)2 activity and protein expression, however, it did not affect HDAC2 mRNA.
      Further studies revealed that baicalin inhibited HDAC2 phosphorylation,
      suggesting that it may directly affect the protein structure and effect by
      modification at post-translational level. Together these results suggest that
      baicalin has anti-inflammatory effects in cigarette smoke induced inflammatory
      models in mice and A549 cells, possibly achieved by modulating HDAC2.

PMID- 22421406
TI  - Blockade of the renin-angiotensin-aldosterone system (RAAS) for primary
      prevention of non-valvular atrial fibrillation: a systematic review and meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: The renin-angiotensin-aldosterone system is suggested to play a key
      role in the development of atrial fibrillation through structural and electrical
      remodeling. This review aims to assess the effectiveness of blockade of the renin
      angiotensin-aldosterone system in the prevention of new onset atrial
      fibrillation. METHODS: Electronic databases from 1984 onwards and previous
      systematic reviews were searched in addition to contacting experts in the field.
      Two reviewers independently selected eligible randomized controlled trials that
      reported on new onset atrial fibrillation, and that compared at least one of the
      following drugs: angiotensin-converting enzyme inhibitors, angiotensin II
      receptor blockers, and aldosterone antagonists with conventional therapy or
      placebo. RESULTS: Fourteen trials including 92,817 randomized patients met the
      inclusion criteria. RAAS inhibition compared with conventional therapy or placebo
      reduced new onset atrial fibrillation (RR=0.79; 95% CI; 0.69-0.90, p
      value<0.001). ARBs showed a strong effect in the reduction of onset atrial
      fibrillation (RR=0.78; 95% CI: 0.66-0.92, p-value=0.009), whereas results for ACE
      inhibitors were not as clear but likely show no effect (RR=0.79, 95% CI: 0.62
      1:00, p-value: 0.05). Aldosterone antagonists, did not appear to play a role in
      the prevention of new onset atrial fibrillation (RR=0.77, 95%CI: 0.55-1.08, p
      value: 0.21). Risk reduction was highest among heart failure patients.
      CONCLUSIONS: RAAS inhibition appears to reduce the risk of developing new onset
      atrial fibrillation in different patient groups with coronary artery disease. Yet
      these results were considered of low quality evidence and therefore further
      research with stronger quality trials is required to confirm current results.

PMID- 22421407
TI  - Determination of ginsenosides Rb1, Rb2, and Rb3 in rat plasma by a rapid and
      sensitive liquid chromatography tandem mass spectrometry method: Application in a
      pharmacokinetic study.
AB  - A sensitive rapid resolution liquid chromatography-tandem mass spectrometry
      method was developed to determine the pharmacokinetics of ginsenoside Rb(1),
      Rb(2), and Rb(3) in rats, after oral administration (50mg/kg) and intravenous
      administration (10mg/kg) of Rb(1), Rb(2), and Rb(3), respectively. The plasma
      samples were extracted by saturated N-butanol with Rg(2) as internal standard.
      Chromatographic separation was performed on a Zorbax SB-C18 column (50 mm * 4.6
      mm, 1.8 MUm) with a mobile phase consisting of methanol and 1mM ammonium formate
      (74:26, v/v). Multiple reaction monitoring mode was performed using the
      fragmentation transitions of m/z 1107.7->m/z 178.9, m/z 1077.7->m/z 148.6, and
      m/z 1077.7->m/z 783.4 for Rb(1), Rb(2), and Rb(3), respectively. Calibration
      curves were recovered over a concentration range of 20-1000 ng/ml for Rb(1) and
      Rb(2), and 50-2500 ng/ml for Rb(3). The limits of detection were 3.0 ng/ml, 4.0
      ng/ml, and 6.5 ng/ml. Both intra-day and inter-day variances were less than 15%
      and the accuracy was within 86-114% for the three ginsenosides. All three
      ginsenosides had poor oral bioavailability (0.78%, 0.08%, and 0.52% for Rb(1),
      Rb(2), and Rb(3), respectively). The value of Rb(1) is higher than that of Rb(2)
      or Rb(3), indicating that ginsenosides with hexose and hydroxyl groups (Rb(1))
      could present better pharmacokinetic behaviors than those with pentose groups in
      the same glycosylation site by oral administration.

PMID- 22421408
TI  - Effect of aspirin administration on reversal of tumor-induced suppression of
      myelopoiesis in T-cell lymphoma bearing host.
AB  - The present investigation studied the effect of aspirin administration in tumor
      bearing hosts on bone marrow cellularity and myelopoiesis. Aspirin administration
      to mice bearing a transplantable T-cell lymphoma, designated as Dalton's lymphoma
      (DL), augmented proliferation of bone marrow cells (BMC). BMC of aspirin
      administered tumor-bearing mice were found to be predominantly in the S phase of
      cell cycle releasing them from G0/G1 arrest. Aspirin-exposed BMC also showed an
      altered expression of survival and cell cycle regulatory proteins p53, bcl2,
      caspase-activated deoxyribonuclease (CAD), cyclin B1 and cyclin D. Moreover, the
      BMC of aspirin-administered tumor-bearing mice showed an augmented colony-forming
      ability and differentiation in the macrophage lineage with an activated phenotype
      of bone marrow-derived macrophages (BMDM) with respect to macrophage-mediated
      tumoricidal activity and production of nitric oxide, IL-1beta, TNFalpha and VEGF.
      On the other hand aspirin administration to normal mice showed little effect on
      bone marrow cellularity and myeloid differentiation. In this model, aspirin had a
      myelopoetic action in tumor-bearing host.

PMID- 22421409
TI  - Evaluation of dysplasia through detailed cytomorphology in 3156 patients from the
      Dusseldorf Registry on myelodysplastic syndromes.
AB  - Using the Dusseldorf MDS registry with standardized cytomorphology we here
      describe dysplastic features in detail, concentrating on 16 different dysplastic
      features in the blood and 19 in the marrow in 3156 patients. The most frequent
      dysplastic features were megaloblastoid changes and bi- and multinuclearity in
      the erythropoiesis, pseudo-Pelger cells and hypogranulation in the granulopoiesis
      and micromegakaryoctes and mononuclear megakaryocytes in the megakaryopoiesis.
      The frequency of dysplastic changes did not differ significantly among the WHO
      types with the exception of MDS with del(5q) and CMML types. No single sign of
      dysplasia is exclusive for the diagnosis of MDS.

PMID- 22421410
TI  - Expression of soluble HLA-G in multiple myeloma patients and patients with renal
      failure.
AB  - Human lymphocyte antigen-G (HLA-G) is an immunosuppressive molecule that induces
      functional silencing of immune component cells and can be responsible for
      immunosuppression in patients with multiple myeloma (MM). Immune dysfunction is
      an important feature of MM and leads to infections as well as may promote disease
      progression. Ninety-five patients were included in this study. In MM, the sHLA-G
      levels were increased when compared to healthy volunteers and the levels of sHLA
      G correlated with concentration of creatinine. Interestingly, we detected high
      levels of sHLA-G in patients with renal insufficiency without any malignant
      disease but levels were lower than in MM.

PMID- 22421411
TI  - Interleukin-6, osteopontin and Raf/MEK/ERK signaling modulate the sensitivity of
      human myeloma cells to alkylphosphocholines.
AB  - Alkylphosphocholines are highly active against multiple myeloma (MM) cells in
      vitro and are devoid of myelotoxicity. Little is known about the determinants of
      MM cell responsiveness or resistance to these drugs. In this study we
      investigated the effects of disease-relevant cytokines, such as interleukin-6 (IL
      6) and osteopontin (OPN), on the in vitro antimyeloma activity of erufosine and
      perifosine. The role of the Raf/MEK/ERK pathway was also studied. Exogenous IL-6
      reduced the cytotoxicity of erufosine against OPM-2 cells and, to a smaller
      extent, against U-266 cells. This was accompanied by inhibition of apoptosis in
      OPM-2 cells. The efficacy of perifosine was similarly affected, but to a greater
      extent. IL-6 slightly enhanced the sensitivity of RPMI-8226 cells to erufosine,
      thus emphasizing the heterogeneity of MM. Induced overexpression of OPN isoforms
      made OPM-2 cells less sensitive to erufosine. In all cases of IL-6- or OPN
      induced resistance, the effective concentrations of erufosine were still within
      the clinically achievable range. Like other alkylphosphocholines, erufosine
      enhanced Raf/MEK/ERK signaling in MM cells but in some cases this contributed to
      cytotoxicity.

PMID- 22421412
TI  - [Black hairy tongue in an infant].

PMID- 22421413
TI  - [Recurrent urticaria and autoimmune thyroiditis: the influence of thyroxine
      treatment on the outcome of the urticaria].

PMID- 22421414
TI  - Immobilization of Candida antarctica A and Thermomyces lanuginosus lipases on
      cotton terry cloth fibrils using polyethyleneimine.
AB  - In this study, cotton terry cloth fibrils were coated with 0.2% polyethyleneimine
      (PEI). Lipases from Candida antarctica A (CALA) and Thermomyces lanuginosus (TL)
      were immobilized on this support through adsorption followed by cross-linking
      with 0.2% glutaraldehyde. PEI-enzyme aggregates formation and growth of
      aggregates on cotton cloth fibrils lead to multilayer immobilization of the
      lipases. PEI and lipase was mixed to form PEI-enzyme complex/aggregate. The
      highest amount of enzyme precipitate was obtained at the PEI to enzyme ratio of
      1/20-1/40 for both lipases. The effect of pH was also investigated for aggregates
      formation. The results showed that when pH values were below 8, aggregation and
      precipitation were not occurred for C. antarctica A lipase. However, pH did not
      affect PEI-enzyme aggregate formation for T. lanuginosus lipase. Immobilized
      enzyme amount was approximately 180 mg/g support and 200 mg/g support for T.
      lanuginosus and C. antarctica A lipases, respectively. Effect of the reaction
      temperature on the relative activity of the free and immobilized lipases at
      various temperature (30-80  degrees C) was studied. It was found that
      immobilization had no effect on the optimum temperature and it was 60  degrees C
      for both free and immobilized enzymes. The effect of operational and storage
      stability on activity of free and immobilized lipases were also investigated.
      Immobilized lipases exhibited that they could be stored at room temperature with
      a little activity lost during 28 days.

PMID- 22421415
TI  - Preparation of vesicle drug carrier from palm oil- and palm kernel oil-based
      glycosides.
AB  - A new mixture of alkyl glycosides derived from palm oil (PO) or palm kernel oil
      (PKO) was synthesised. This mixture contains glycosylated disaccharide of either
      maltose or lactose with aliphatic chain that varies according to the PO or PKO
      fatty acids composition. The synthesis method produced no polymerised sugar
      unlike the production of the commercial glycosides (APG). The mixture only
      contains various glycosides differing by the alkyl chain and stereoisomers. Three
      anomeric mixtures can be produced depending on the reaction time and catalyst:
      alpha-dominant mixture, beta-dominant mixture and equal mixture. The PO and PKO
      derived glycosides were able to form a stable vesicle with a small amount of
      dicetyl phosphate (DCP) and showed high vitamin E encapsulation efficiency. Low
      packing density of the membrane bilayer enabled more vitamin E to participate in
      the membrane formation. The anomeric mixtures of the maltosides provide no
      difference in membrane packing behaviour as it was governed by the hydrophilic
      region. Significant difference in membrane packing density was observed for
      lactosides anomeric mixtures because the packing behaviour was influenced by the
      hydrophobic region. Inclusion of cholesterol led to decrease in vitamin E
      encapsulation as well as reducing the stability of the vesicle system. The
      vesicular formulations of the glycosides were stable for 3 months when stored at
      refrigeration temperature.

PMID- 22421416
TI  - Probing nanoparticle interactions in cell culture media.
AB  - Nanoparticle research is often performed in vitro with little emphasis on the
      potential role of cell culture medium. In this study, gold nanoparticle
      interactions with cell culture medium and two cancer cell lines (human T-cell
      leukemia Jurkat and human pancreatic carcinoma PANC1) were investigated. Gold
      nanoparticles of 10, 25, 50, and 100 nm in diameter at fixed mass concentration
      were tested. Size distributions and zeta potentials of gold nanoparticles
      suspended in deionized (DI) water and Dulbecco's Modified Eagle's Media (DMEM)
      supplemented with fetal calf serum (FCS) were measured using dynamic light
      scattering (DLS) technique. In DI water, particle size distributions exhibited
      peaks around their nominal diameters. However, the gold nanoparticles suspended
      in DMEM supplemented with FCS formed complexes around 100 nm, regardless of their
      nominal sizes. The DLS and UV-vis spectroscopy results indicate gold nanoparticle
      agglomeration in DMEM that is not supplemented by FCS. The zeta potential results
      indicate that protein rich FCS increases the dispersion quality of gold
      nanoparticle suspensions through steric effects. Cellular uptake of 25 and 50 nm
      gold nanoparticles by Jurkat and PANC1 cell lines were investigated using
      inductively coupled plasma-mass spectroscopy. The intracellular gold level of
      PANC1 cells was higher than that of Jurkat cells, where 50 nm particles enter
      cells at faster rates than the 25 nm particles.

PMID- 22421417
TI  - Temperature-modulated adsorption of poly(N-isopropylacrylamide)-grafted ferritin
      on solid substrate.
AB  - Ferritin grafted with temperature-responsive poly(N-isopropylacrylamide) (PIPAAm
      ferritin) was synthesized by a coupling reaction using PIPAAm and ferritin for
      obtaining stimuli-responsive biomaterials. The hydrodynamic diameter of PIPAAm
      ferritins in aqueous solution increased at 37  degrees C at a higher protein
      concentration (>0.2mg/mL) because of the intermolecular aggregation through the
      hydrophobic interaction of PIPAAm chains. On the other hand, PIPAAm-ferritins at
      a lower concentration (<0.2mg/mL) were unable to increase their size even at 37 
      degrees C. The adsorption kinetics of PIPAAm-ferritins on hydrophobically
      modified Si substrate were evaluated with a quartz crystal microbalance in 10
      mmol/L Bis-Tris/HCl buffer (pH 5.8) with and without poly(oxyethylene) sorbitan
      monolaurate (TWEEN 20) (0.05 wt%) as a surfactant. Although the adsorption of
      PIPAAm-ferritins on hydrophobic Si substrate at 25  degrees C in the buffer with
      TWEEN 20 was hardly observed, PIPAAm-ferritins were considerably adsorbed on the
      substrate at 37  degrees C, indicating that the hydrophobic interaction between
      the substrate and PIPAAm grafts on the ferritins after the destruction of the
      hydrophobic interaction between the protein and the substrate by TWEEN 20.

PMID- 22421418
TI  - Optimization of x-ray spectra in digital mammography through Monte Carlo
      simulations.
AB  - In this work, a Monte Carlo code was used to investigate the performance of
      different x-ray spectra in digital mammography, through a figure of merit (FOM),
      defined as FOM = CNR2/(-)D(g), with CNR being the contrast-to-noise ratio in
      image and [Formula: see text] being the average glandular dose. The FOM was
      studied for breasts with different thicknesses t (2 cm <= t <= 8 cm) and
      glandular contents (25%, 50% and 75% glandularity). The anode/filter combinations
      evaluated were those traditionally employed in mammography (Mo/Mo, Mo/Rh, Rh/Rh),
      and a W anode combined with Al or K-edge filters (Zr, Mo, Rh, Pd, Ag, Cd, Sn),
      for tube potentials between 22 and 34 kVp. Results show that the W anode combined
      with K-edge filters provides higher values of FOM for all breast thicknesses
      investigated. Nevertheless, the most suitable filter and tube potential depend on
      the breast thickness, and for t >= 6 cm, they also depend on breast glandularity.
      Particularly for thick and dense breasts, a W anode combined with K-edge filters
      can greatly improve the digital technique, with the values of FOM up to 200%
      greater than that obtained with the anode/filter combinations and tube potentials
      traditionally employed in mammography. For breasts with t < 4 cm, a general good
      performance was obtained with the W anode combined with 60 MUm of the Mo filter
      at 24-25 kVp, while 60 MUm of the Pd filter provided a general good performance
      at 24-26 kVp for t = 4 cm, and at 28-30 and 29-31 kVp for t = 6 and 8 cm,
      respectively.

PMID- 22421419
TI  - Losing my grip.

PMID- 22421420
TI  - Cerebral oxygen saturation measured by near-infrared spectroscopy and jugular
      venous bulb oxygen saturation during arthroscopic shoulder surgery in beach chair
      position under sevoflurane-nitrous oxide or propofol-remifentanil anesthesia.
AB  - BACKGROUND: We examined the effects of different anesthetics on cerebral
      oxygenation and systemic hemodynamics in patients undergoing surgery in beach
      chair position (BCP). Jugular venous bulb oxygen saturation (SjvO2) and regional
      cerebral tissue oxygen saturation (SctO2) were determined while patients were
      placed from the supine to BCP. Whether SctO2 and SjvO2 are interchangeable in
      assessing the cerebral oxygenation was also examined. METHODS: Forty patients
      undergoing shoulder surgery in BCP were randomly assigned to receive sevoflurane
      nitrous oxide (S/N) or propofol-remifentanil (P/R) anesthesia. Four patients
      taking angiotensin II receptor antagonists were excluded post hoc. Mean arterial
      pressure and heart rate, as well as SjvO2 and SctO2, were measured before
      (postinduction baseline in supine position) and after BCP. RESULTS: Mean arterial
      pressure decreased by BCP in both groups. It was, however, significantly higher
      in S/N (n = 19) than in P/R group (n = 17) at 7 to 8 min after the positioning.
      SjvO2 also significantly decreased after BCP in both groups, the magnitude of
      which was lower in S/N than in P/R group (11 +/- 10% vs. 23 +/- 9%, P = 0.0006).
      The incidences of SjvO2 <50% and mean arterial pressure less than 50 mmHg were
      lower in S/N group, but SctO2and the incidence of cerebral desaturation (more
      than 20% decrease from baseline) did not significantly differ between the groups.
      SctO2 and SjvO2 were only weakly correlated (beta = 0.218, r2 = 0.133). Bland
      Altman analysis showed a mean difference of -7.2% with 95% limit of agreement
      between -38.2% and 23.8%. CONCLUSIONS: The margin of safety against impaired
      cerebral oxygenation is greater and SjvO2 is more preserved with S/N than with
      P/R anesthesia. SctO2 may not be reliable in detecting a low SjvO2 during the
      surgery in BCP.

PMID- 22421421
TI  - Intracranial self-stimulation of the paraventricular nucleus of the hypothalamus:
      increased faciliation by morphine compared to cocaine.
AB  - BACKGROUND: Neuropathic pain attenuates opioid facilitation of rewarding
      electrical stimulation of limbic dopaminergic pathways originating from the
      ventral tegmental area. Whether neuropathic pain alters opioid effects of other
      brain-reward systems is unknown. METHODS: Control and spinal nerve-ligated (SNL)
      rats had electrodes implanted into the paraventricular nucleus (PVN) of the
      hypothalamus or medial forebrain bundle. Control and SNL rats were trained to
      lever-press for intracranial self-stimulation (ICSS), and modulation by morphine
      or cocaine was assessed. RESULTS: Control and SNL rats lever-pressed for
      stimulation of the PVN and medial forebrain bundle. Morphine produced greater
      reductions in the frequency at which rats emitted 50% of maximal responding for
      PVN ICSS (maximal effect 24.67 +/- 4.60 [mean +/- SEM] and 24.11 +/- 5.96 in SNL
      [n = 6] and control [n = 8] rats, respectively, compared with medial forebrain
      bundle ICSS (12.38 +/- 6.77 [n = 8] and 12.69 +/- 1.55 [n = 7]). In contrast,
      cocaine was less efficacious in potentiating PVN ICSS (maximal effect 11.76 +/-
      2.86 and 12.38 +/- 4.01 in SNL [n = 12] and control [n = 8] rats, respectively)
      compared with medial forebrain bundle ICSS (30.58 +/- 3.40 [n = 9] and 27.55 +/-
      4.51 [n = 7]). CONCLUSIONS: PVN ICSS is facilitated to a greater extent by
      morphine than cocaine, and the effects of each drug on this behavior are
      unaltered after spinal nerve ligation. These effects contrast those observed with
      direct stimulation of limbic dopamine pathways, suggesting that the PVN may have
      a greater role in the reinforcing effects of opioids than classic limbic regions,
      particularly in the presence of chronic pain.

PMID- 22421422
TI  - Interaction between polymeric multilayer capsules and immune cells.
AB  - Polymeric multilayer capsules are emerging carrier systems in the field of drug
      delivery. These materials are fabricated by set-wise assembly of interaction
      species onto a sacrificial template followed by the decomposition of this
      template, yielding hollow capsules. Using bio-responsive polymers that can be
      triggered by pH, enzymes or reduction, several groups are exploring these systems
      for intracellular drug delivery. In this review we focus on the recent efforts
      made in investigating the in vitro and in vivo interaction between these capsules
      and cells of the immune system.

PMID- 22421423
TI  - E-selectin liposomal and nanotube-targeted delivery of doxorubicin to circulating
      tumor cells.
AB  - The presence of circulating tumor cells (CTCs) is believed to lead to the
      formation of secondary tumors via an adhesion cascade involving interaction
      between adhesion receptors of endothelial cells and ligands on CTCs. Many CTCs
      express sialylated carbohydrate ligands on their surfaces that adhere to selectin
      protein found on inflamed endothelial cells. We have investigated the feasibility
      of using immobilized selectin proteins as a targeting mechanism for CTCs under
      flow. Herein, targeted liposomal doxorubicin (L-DXR) was functionalized with
      recombinant human E-selectin (ES) and polyethylene glycol (PEG) to target and
      kill cancer cells under shear flow, both when immobilized along a microtube
      device or sheared in a cone-and-plate viscometer in a dilute suspension. Healthy
      circulating cells such as red blood cells were not targeted by this mechanism and
      were left to freely circulate, and minimal leukocyte death was observed.
      Halloysite nanotube (HNT)-coated microtube devices immobilized with nanoscale
      liposomes significantly enhanced the targeting, capture, and killing of cancer
      cells. This work demonstrates that E-selectin functionalized L-DXR, sheared in
      suspension or immobilized onto microtube devices, provides a novel approach to
      selectively target and deliver chemotherapeutics to CTCs in the bloodstream.

PMID- 22421424
TI  - Doxorubicin-conjugated chimeric polypeptide nanoparticles that respond to mild
      hyperthermia.
AB  - This paper reports the design, physicochemical characterization and in vitro
      cytotoxicity of a thermally responsive chimeric polypeptide (CP), derived from an
      elastin-like polypeptide (ELP). The CP self-assembles into ~40 nm diameter
      nanoparticles upon conjugation of multiple copies of doxorubicin (Dox), and
      displays a nanoparticle-to-aggregate phase transition between 39 and 42  degrees
      C in media, a temperature range suitable for mild hyperthermia of solid tumors.
      The CP-Dox nanoparticle is stable upon dilution to low micromolar concentrations,
      and is cytotoxic at both 37 and 42  degrees C. A thermally responsive
      nanoparticle formulation of Dox may prove to be broadly useful in hyperthermia
      targeted chemotherapy of a variety of solid tumors.

PMID- 22421425
TI  - Hydrogels for protein delivery in tissue engineering.
AB  - Tissue defects caused by diseases or trauma present enormous challenges in
      regenerative medicine. Recently, a better understanding of the biological
      processes underlying tissue repair led to the establishment of new approaches in
      tissue engineering which comprise the combination of biodegradable scaffolds and
      appropriate cells together with specific environmental cues, such as growth or
      adhesive factors. These factors (in fact proteins) have to be loaded and
      sustainably released from the scaffolds in time. This review provides an overview
      of the various hydrogel technologies that have been proposed to control the
      release of bioactive molecules of interest for tissue engineering applications.
      In particular, after a brief introduction on bioactive protein drugs that have
      remarkable relevance for tissue engineering, this review will discuss their
      release mechanisms from hydrogels, their encapsulation and immobilization methods
      and will overview the main classes of hydrogel forming biomaterials used in vitro
      and in vivo to release them. Finally, an outlook on future directions and a
      glimpse into the current clinical developments are provided.

PMID- 22421426
TI  - Prevention of infusion reactions to PEGylated liposomal doxorubicin via
      tachyphylaxis induction by placebo vesicles: a porcine model.
AB  - PEGylated liposomal doxorubicin (Doxil) has been used in cancer chemotherapy for
      16 years. Clinical experience shows that it can cause mild-to-severe
      hypersensitivity (infusion) reactions, which are manifestations of complement (C)
      activation-related pseudoallergy (CARPA). Although in most cases CARPA is
      inconsequential, a main symptom, cardiopulmonary distress, may be life
      threatening in hypersensitive individuals. To date, the prevention of Doxil
      induced CARPA is based on premedication and a slow infusion protocol. The present
      study suggests desensitization by Doxil-like empty liposomes, called placebo
      Doxil (Doxebo), as an alternative strategy, which is based on the tachyphylactic
      nature of Doxil reactions. Doxebo-induced tolerance to Doxil was shown to develop
      within minutes and to be specific to Doxil-like PEGylated liposomes. The
      procedure of desensitization involves slow, low-dose pre-infusion of Doxebo
      before Doxil treatment which minimizes the ensuing physiological changes or keeps
      them subclinical. Although the mechanism of tolerance induction is not yet clear,
      the effector arm of C response is unlikely to be affected, as the vascular
      reactivity of desensitized pigs to zymosan remains intact. Desensitization with
      empty vesicles represents a novel approach for reducing the risk of anaphylactic
      reactions to drug carrier liposomes. The underlying immediate, most likely
      passive silencing of an innate immune response may represent a novel mechanism of
      tolerance induction which may work for other reactogenic nanosystems as well.

PMID- 22421427
TI  - Sickness absence because of musculoskeletal diagnoses and risk of all-cause and
      cause-specific mortality: a nationwide Swedish cohort study.
AB  - Knowledge regarding mortality as a potential consequence of being sickness absent
      because of musculoskeletal diagnoses is almost nonexistent. The association
      between sickness absence because of musculoskeletal diagnoses and risk of
      premature death was examined in a prospective, nationwide, population-based
      cohort study based on Swedish registers. Included were all 4,760,987 individuals
      who were living in Sweden December 31, 2005, aged 20 to 64 years, and not on
      disability or old-age pension. Those sickness absent in 2005 because of
      musculoskeletal diagnoses were compared to those sickness absent because of non
      musculoskeletal diagnoses and to those with no sickness absence. Musculoskeletal
      diagnoses were categorized as follows: 1) artropathies/systemic connective tissue
      disorders; 2) dorsopathies; and 3) soft tissue
      disorders/osteopathies/chondropathies/other musculoskeletal disorders. All-cause
      mortality was followed from 2006 to 2009 and cause-specific mortality was
      followed from 2006 to 2008. Hazard ratios (HRs) and 95% confidence intervals
      (CIs) were estimated using Cox regression. In models adjusted for socio
      demographic factors, and morbidity, sickness absence because of all 3 categories
      of musculoskeletal diagnoses was associated with 1.3- to 1.5-fold increased risks
      of all-cause mortality (adjusted model, category 1 diagnoses, HR=1.50, 95%
      CI=1.38-1.63). Similar associations were observed among both women and men.
      Moreover, increased mortality risks due to tumors (HR=1.6-1.7), circulatory
      diseases (HR=1.2-1.5), mental disorders (HR=1.2-3.2), and suicide (HR=1.5-1.9)
      were observed among persons sickness absent because of musculoskeletal diagnoses.
      This nationwide cohort study reveals, for the first time, an increased risk of
      premature death among both women and men sickness absent because of
      musculoskeletal diagnoses after adjustment for several potential confounders.

PMID- 22421428
TI  - Is touch gating due to sensory or cognitive interference?
AB  - Touch gating, the attenuation of tactile sensitivity in the presence of pain, is
      a well-documented phenomenon, but its mechanism is unknown. The ability of pain
      to capture attention suggests that touch gating may be an example of distraction,
      but the fact that pain raises tactile but not auditory thresholds argues that
      touch gating is a form of somatosensory interaction. Therefore, the present study
      was carried out to determine whether touch gating is the result of sensory or
      cognitive interference. Touch gating was repeatedly produced by delivering a
      colocalized painful heat stimulus (45 degrees C) during forced-choice
      measurements of vibration threshold on the palm. Noxious heat significantly
      increased thresholds compared with those measured at normal skin temperature, and
      this interference did not decline over the course of an extended series of
      experiments during which pain intensity significantly habituated. Touch gating
      was thus related to the constant physical intensity, rather than to the changing
      subjective intensity, of the noxious stimulus. For comparison, a form of
      unambiguously cognitive interference, the Stroop effect, was also measured
      repeatedly; it declined significantly across sessions, unlike touch gating
      interference. Finally, touch gating was not correlated with measures of
      participants' distractibility, fear of pain, hypervigilance, or anxiety,
      variables previously found to influence pain on a cognitive level. Taken
      together, the results suggest that touch gating is a robust, stimulus-locked form
      of sensory interaction, rather than a transitory result of distraction or other
      cognitive processes.

PMID- 22421429
TI  - Organochlorine residue and toxic metal (Pb, Cd and Cr) levels in the surface
      sediments of the Marmara Sea and the coast of Istanbul, Turkey.
AB  - In this study, organochlorine and toxic metal (Pb, Cd and Cr) analyses have been
      done in the surface sediments. Sediment samples have been collected from 7 parts
      of the Marmara Sea and the coast of Istanbul during 2009. Total Pb, Cd and Cr
      contents vary between 32 MUg g(-1) and 122 MUg g(-1); 0.19 MUg g(-1) and 1.16 MUg
      g(-1); 62 MUg g(-1) and 372 MUg g(-1), respectively. EF values of Pb and Cr are
      higher than 1.5 in all the stations. EF value of Cd is considerably high at
      Station MY1 (Tuzla Port). Total organochlorine residue contents range between
      4.33 ng g(-1) and 22.2 ng g(-1) in the surface sediments.

PMID- 22421430
TI  - Whole-body distribution and radiation dosimetry of [11C]telmisartan as a
      biomarker for hepatic organic anion transporting polypeptide (OATP) 1B3.
AB  - INTRODUCTION: Telmisartan, a nonpeptide angiotensin II AT1 receptor antagonist
      used as an antihypertensive drug, is specifically taken up by the liver through
      the OATP1B3. PET imaging with [(11)C]telmisartan is expected to provide
      information about the whole body pharmacokinetics of telmisartan as well as its
      transport property by OATP1B3. The purpose of the study was to determine the
      biodistribution and radiation dosimetry of [(11)C]telmisartan in humans. METHODS:
      Biodistribution of [(11)C]telmisartan was measured in three rats and six healthy
      male human volunteers. In the rat study, a dynamic emission scan was performed
      for 90 min. In the human study, dynamic whole-body PET images were acquired after
      intravenous injection of [(11)C]telmisartan. ROIs were defined for source organs
      on the PET images to measure time-course of [(11)C]telmisartan uptake as
      percentage injected dose and the number of disintegration for each organ.
      Radiation dosimetry was calculated with OLINDA/EXM. RESULTS: In the rat study,
      most radioactivity was rapidly taken up by the liver and part of it was excreted
      into the biliary tract and intestine. Extrapolating from the rat data, the
      effective dose for the adult human being was estimated to be 3.65+/-0.01
      microSv/MBq (n=3). In the human study, most of the tracer was taken up by the
      liver as well, although not as rapidly as in the rat. The activity in the gall
      bladder and intestine increased gradually. The effective dose for the adult human
      being was 4.24+/-0.09 microSv/MBq (n=6). CONCLUSIONS: [(11)C]Telmisartan is a
      safe PET tracer with a dosimetry profile comparable to other common (11)C PET
      tracers.

PMID- 22421431
TI  - In vivo and in vitro evaluation of Cy5.5 conjugated epidermal growth factor
      receptor binding peptide.
AB  - The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor and
      plays an important role in carcinogenesis. In this study, the epidermal growth
      factor receptor binding peptide (EGBP) was identified using a phage display
      method and evaluated in U87MG cells in order to investigate the possibility to
      target the EGFR using an optical imaging system. Cyanine dye 5.5 (Cy5.5) was
      conjugated with EGBP-GGG-SC, EGBP-AOC-SC, and EGBP-AM2BA-SC. Cellular binding
      study of EGBP-Linker-Cy5.5 conjugates or (125)I-EGBP-Linker compounds was
      performed in U87MG cells. Optical imaging studies were performed in U87MG bearing
      mice. Three of seven clones from the 12-mer peptide library showed a specific
      binding affinity to rhEGFR, and they encoded the same 12 amino acid peptide
      sequence, FPMFNHWEQWPP. Confocal images show that the fluorescent signal of EGBP
      Linker-Cy5.5 conjugates was decreased in the order: EGBP-AOC-Cy5.5?EGBP-AM2BA
      Cy5.5>EGBP-GGG-Cy5.5. EGBP-AOC-Cy5.5 appeared in cell cytoplasm and surface, and
      it was inhibited by free EGBP apparently. The cellular binding of EGBP-AOC-Cy5.5
      exhibited a higher average radiance value than EGBP-GGG-Cy5.5 and EGBP-AM2BA
      Cy5.5. Among various (125)I-EGBP-Linker compounds, EGBP-GGG showed a higher
      binding than other compounds. However, uptake of (125)I-EGBP-AOC was clearly
      inhibited by free EGBP in inhibition study. In an in vivo study, the fluorescent
      signal of EGBP-AOC-Cy5.5 treated mouse was mainly detected in the tumor and
      kidney. Among the three derivatives, EGBP-AOC-Cy5.5 was the optimized optical
      imaging agent for U87MG EGFR positive tumors in the animal model. This study
      demonstrated the EGBP-Linker-Cy5.5 conjugates may be useful as a potential EGFR
      target optical probe.

PMID- 22421432
TI  - Direct observation of multiple misfolding pathways in a single prion protein
      molecule.
AB  - Protein misfolding is a ubiquitous phenomenon associated with a wide range of
      diseases. Single-molecule approaches offer a powerful tool for deciphering the
      mechanisms of misfolding by measuring the conformational fluctuations of a
      protein with high sensitivity. We applied single-molecule force spectroscopy to
      observe directly the misfolding of the prion protein PrP, a protein notable for
      having an infectious misfolded state that is able to propagate by recruiting
      natively folded PrP. By measuring folding trajectories of single PrP molecules
      held under tension in a high-resolution optical trap, we found that the native
      folding pathway involves only two states, without evidence for partially folded
      intermediates that have been proposed to mediate misfolding. Instead, frequent
      but fleeting transitions were observed into off-pathway intermediates. Three
      different misfolding pathways were detected, all starting from the unfolded
      state. Remarkably, the misfolding rate was even higher than the rate for native
      folding. A mutant PrP with higher aggregation propensity showed increased
      occupancy of some of the misfolded states, suggesting these states may act as
      intermediates during aggregation. These measurements of individual misfolding
      trajectories demonstrate the power of single-molecule approaches for
      characterizing misfolding directly by mapping out nonnative folding pathways.

PMID- 22421433
TI  - Lipid-derived nanoparticles for immunostimulatory RNA adjuvant delivery.
AB  - The specific activation of Toll-like receptors (TLRs) has potential utility for a
      variety of therapeutic indications including antiviral immunotherapy and as
      vaccine adjuvants. TLR7 and TLR 8 may be activated by their native ligands,
      single-stranded RNA, or by small molecules of the imidazoquinoline family.
      However the use of TLR7/8 agonists for in vivo therapy is limited by instability,
      in the case of RNA, or systemic biodistribution and toxicity in the case of small
      molecule agonists. We hypothesized that unique lipid-like materials, termed
      "lipidoids," could be designed to efficiently deliver immunostimulatory RNA
      (isRNA) to TLR-expressing cells to drive innate and adaptive immune responses. A
      library of lipidoids was synthesized and screened for the ability to induce type
      I IFN activation in human peripheral blood mononuclear cells when combined with
      isRNA oligonucleotides. Effective lipidoid-isRNA nanoparticles, when tested in
      mice, stimulated strong IFN-alpha responses following subcutaneous injection, had
      robust antiviral activity that suppressed influenza virus replication, and
      enhanced antiovalbumin humoral and cell-mediated responses when used as a vaccine
      adjuvant. Further, we demonstrate that whereas all immunological activity was
      MyD88-dependent, certain materials were found to engage both TLR7-dependent and
      TLR7-independent activity in the mouse suggestive of cell-specific delivery.
      These lipidoid formulations, which are materials designed specifically for
      delivery of isRNA to Toll-like receptors, were superior to the commonly used N-[1
      (2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate-RNA delivery
      system and may provide new tools for the manipulation of TLR responses in vitro
      and in vivo.

PMID- 22421434
TI  - Divergent role of the Hox gene Antennapedia in spiders is responsible for the
      convergent evolution of abdominal limb repression.
AB  - Evolution often results in morphologically similar solutions in different
      organisms, a phenomenon known as convergence. However, there is little knowledge
      of the processes that lead to convergence at the genetic level. The genes of the
      Hox cluster control morphology in animals. They may also be central to the
      convergence of morphological traits, but whether morphological similarities also
      require similar changes in Hox gene function is disputed. In arthropods, body
      subdivision into a region with locomotory appendages ("thorax") and a region with
      reduced appendages ("abdomen") has evolved convergently in several groups, e.g.,
      spiders and insects. In insects, legs develop in the expression domain of the Hox
      gene Antennapedia (Antp), whereas the Hox genes Ultrabithorax (Ubx) and abdominal
      A mediate leg repression in the abdomen. Here, we show that, unlike Antp in
      insects, the Antp gene in the spider Achaearanea tepidariorum represses legs in
      the first segment of the abdomen (opisthosoma), and that Antp and Ubx are
      redundant in the following segment. The down-regulation of Antp in A.
      tepidariorum leads to a striking 10-legged phenotype. We present evidence from
      ectopic expression of the spider Antp gene in Drosophila embryos and imaginal
      tissue that this unique function of Antp is not due to changes in the Antp
      protein, but likely due to divergent evolution of cofactors, Hox collaborators or
      target genes in spiders and flies. Our results illustrate an interesting example
      of convergent evolution of abdominal leg repression in arthropods by altering the
      role of distinct Hox genes at different levels of their action.

PMID- 22421435
TI  - Shaggy/glycogen synthase kinase 3beta and phosphorylation of Sarah/regulator of
      calcineurin are essential for completion of Drosophila female meiosis.
AB  - The Ca(2+)/Calmodulin-dependent phosphatase calcineurin is essential for exit
      from meiotic arrest at metaphases I and II in Drosophila and Xenopus oocytes. We
      previously found that Sarah, the Drosophila homolog of regulator of calcineurin,
      acts as a positive regulator of calcineurin and is required to complete anaphase
      I of female meiosis. Here, we undertook biochemical approaches, including MS and
      posttranslational modification analyses, to better understand the mechanism by
      which Sarah regulates calcineurin. A search for phosphorylated residues revealed
      that Sarah is highly phosphorylated at Ser100, Thr102, and Ser219 in both ovaries
      and activated eggs and that Ser215 is phosphorylated only in activated eggs.
      Functional analyses using mutant forms of Sarah showed that phosphorylation at
      Ser215, a consensus phosphorylation site for glycogen synthase kinase 3beta (GSK
      3beta) and its priming kinase site Ser219, are essential for Sarah function.
      Furthermore, germ-line clones homozygous for a null allele of shaggy (Drosophila
      GSK-3beta) both fail to complete meiosis and lack phosphorylation of Sarah at
      Ser215, suggesting that the phosphorylation of Sarah by Shaggy/GSK-3beta is
      required to complete meiosis. Our findings suggest a mechanism in which
      Shaggy/GSK-3beta activates calcineurin through Sarah phosphorylation on egg
      activation in Drosophila.

PMID- 22421437
TI  - Permian Coal Forest offers a glimpse of late Paleozoic ecology.

PMID- 22421436
TI  - Neuronal adenosine release, and not astrocytic ATP release, mediates feedback
      inhibition of excitatory activity.
AB  - Adenosine is a potent anticonvulsant acting on excitatory synapses through A1
      receptors. Cellular release of ATP, and its subsequent extracellular enzymatic
      degradation to adenosine, could provide a powerful mechanism for astrocytes to
      control the activity of neural networks during high-intensity activity. Despite
      adenosine's importance, the cellular source of adenosine remains unclear. We
      report here that multiple enzymes degrade extracellular ATP in brain tissue,
      whereas only Nt5e degrades AMP to adenosine. However, endogenous A1 receptor
      activation during cortical seizures in vivo or heterosynaptic depression in situ
      is independent of Nt5e activity, and activation of astrocytic ATP release via
      Ca(2+) photolysis does not trigger synaptic depression. In contrast, selective
      activation of postsynaptic CA1 neurons leads to release of adenosine and synaptic
      depression. This study shows that adenosine-mediated synaptic depression is not a
      consequence of astrocytic ATP release, but is instead an autonomic feedback
      mechanism that suppresses excitatory transmission during prolonged activity.

PMID- 22421438
TI  - Structure of TIGIT immunoreceptor bound to poliovirus receptor reveals a cell
      cell adhesion and signaling mechanism that requires cis-trans receptor
      clustering.
AB  - Nectins (nectin1-4) and Necls [nectin-like (Necl1-5)] are Ig superfamily cell
      adhesion molecules that regulate cell differentiation and tissue morphogenesis.
      Adherens junction formation and subsequent cell-cell signaling is initiated by
      the assembly of higher-order receptor clusters of cognate molecules on juxtaposed
      cells. However, the structural and mechanistic details of signaling cluster
      formation remain unclear. Here, we report the crystal structure of poliovirus
      receptor (PVR)/Nectin-like-5/CD155) in complex with its cognate immunoreceptor
      ligand T-cell-Ig-and-ITIM-domain (TIGIT). The TIGIT/PVR interface reveals a
      conserved specific "lock-and-key" interaction. Notably, two TIGIT/PVR dimers
      assemble into a heterotetramer with a core TIGIT/TIGIT cis-homodimer, each TIGIT
      molecule binding one PVR molecule. Structure-guided mutations that disrupt the
      TIGIT/TIGIT interface limit both TIGIT/PVR-mediated cell adhesion and TIGIT
      induced PVR phosphorylation in primary dendritic cells. Our data suggest a cis
      trans receptor clustering mechanism for cell adhesion and signaling by the
      TIGIT/PVR complex and provide structural insights into how the PVR family of
      immunoregulators function.

PMID- 22421439
TI  - Mixed lineage kinase domain-like is a key receptor interacting protein 3
      downstream component of TNF-induced necrosis.
AB  - Tumor necrosis factor (TNF) is an important inflammatory cytokine and induces
      many cellular responses, including inflammation, cell proliferation, apoptosis,
      and necrosis. It is known that receptor interacting protein (RIP) kinases, RIP1
      and RIP3, are key effectors of TNF-induced necrosis, but little is known about
      how these two RIP kinases mediate this process, although reactive oxygen species
      (ROS) generation and JNK activation have been suggested to be two downstream
      events of RIP kinases. Here we report the identification of mixed lineage kinase
      domain-like, MLKL, as a key RIP3 downstream component of TNF-induced necrosis.
      Through screening a kinase/phosphatase shRNA library in human colon
      adenocarcinoma HT-29 cells, we found that knockdown of MLKL blocked TNF-induced
      necrosis. Our data suggest that MLKL functions downstream of RIP1 and RIP3 and is
      recruited to the necrosome through its interaction with RIP3. Finally, we found
      that MLKL is required for the generation of ROS and the late-phase activation of
      JNK during TNF-induced necrosis. However, because these two events are not
      involved in TNF-induced necrosis in HT-29 cells, the target of MLKL during TNF
      induced necrosis remains elusive. Taken together, our study suggests that MLKL is
      a key RIP3 downstream component of TNF-induced necrotic cell death.

PMID- 22421441
TI  - Doxycycline treatment attenuates acute lung injury in mice infected with virulent
      influenza H3N2 virus: involvement of matrix metalloproteinases.
AB  - Acute respiratory distress syndrome, a severe form of acute lung injury (ALI), is
      a major cause of death during influenza pneumonia. We have provided evidence for
      the involvement of recruited neutrophils, their toxic enzymes such as
      myeloperoxidase and matrix metalloproteinases (MMPs), and neutrophil
      extracellular traps in aggravating alveolar-capillary damage. In this study, we
      investigated the effects of doxycycline (DOX), an inhibitor of MMPs, on influenza
      induced ALI. BALB/c mice were infected with a sublethal dose of mouse-adapted
      virulent influenza A/Aichi/2/68 (H3N2) virus, and administered daily with 20mg/kg
      or 60 mg/kg DOX orally. The effects of DOX on ALI were determined by measuring
      inflammation, capillary leakage, and MMP activities. Furthermore, levels of T1
      alpha (a membrane protein of alveolar type I epithelium) and thrombomodulin (an
      endothelial protein) in the bronchoalveolar lavage fluid were evaluated by
      Western blot analysis. Our results demonstrate significantly decreased
      inflammation and protein leakage in the lungs after DOX treatment. Levels of MMP
      2 and MMP-9 activity, T1-alpha and thrombomodulin were also diminished in the DOX
      treated group. These findings were corroborated by histopathologic analyses,
      which demonstrated significant reduction in lung damage. Although DOX treatment
      reduced ALI, there were no effects on virus titers and body weights. Taken
      together, these results demonstrate that DOX may be useful in ameliorating ALI
      during influenza pneumonia. Further studies are warranted to determine whether
      DOX can be used in combination with anti-viral agents to alleviate severe
      influenza pneumonia.

PMID- 22421440
TI  - Sleeping Beauty mutagenesis reveals cooperating mutations and pathways in
      pancreatic adenocarcinoma.
AB  - Pancreatic cancer is one of the most deadly cancers affecting the Western world.
      Because the disease is highly metastatic and difficult to diagnosis until late
      stages, the 5-y survival rate is around 5%. The identification of molecular
      cancer drivers is critical for furthering our understanding of the disease and
      development of improved diagnostic tools and therapeutics. We have conducted a
      mutagenic screen using Sleeping Beauty (SB) in mice to identify new candidate
      cancer genes in pancreatic cancer. By combining SB with an oncogenic Kras allele,
      we observed highly metastatic pancreatic adenocarcinomas. Using two independent
      statistical methods to identify loci commonly mutated by SB in these tumors, we
      identified 681 loci that comprise 543 candidate cancer genes (CCGs); 75 of these
      CCGs, including Mll3 and Ptk2, have known mutations in human pancreatic cancer.
      We identified point mutations in human pancreatic patient samples for another 11
      CCGs, including Acvr2a and Map2k4. Importantly, 10% of the CCGs are involved in
      chromatin remodeling, including Arid4b, Kdm6a, and Nsd3, and all SB tumors have
      at least one mutated gene involved in this process; 20 CCGs, including Ctnnd1,
      Fbxo11, and Vgll4, are also significantly associated with poor patient survival.
      SB mutagenesis provides a rich resource of mutations in potential cancer drivers
      for cross-comparative analyses with ongoing sequencing efforts in human
      pancreatic adenocarcinoma.

PMID- 22421442
TI  - Autoreactive antibodies raised by self derived de novo peptides can identify
      unrelated antigens on protein microarrays. Are autoantibodies really
      autoantibodies?
AB  - The development of arrays of human proteins has been a huge boon to the search
      for autoantibody diagnostics. Typically, slides with thousands of recombinant
      human proteins arrayed in an addressable fashion are incubated with sera from
      diseased or normal people. If an antibody binds a protein more in the diseased
      than in the normal cohort it is considered an autoantibody response. It is
      usually presumed that the autoantibody was elicited by the protein bound on the
      array. However, our studies using human protein and random peptide arrays
      indicate that antibody specificity may not be as high as commonly thought.
      Therefore we have tested the assumption of the source of autoantibodies. One test
      was to generate antibodies to two totally random peptides and bind these
      antibodies to a human protein array. One of the antibodies generated bound two
      human proteins. A second test was to generate an antibody to a frameshift peptide
      occurring in cancers. This antibody also bound several proteins on the array. We
      conclude that one should be cautious about assuming a particular autoantibody
      target on an array which elicited the original immune response.

PMID- 22421443
TI  - Characterization of solid polymer dispersions of active pharmaceutical
      ingredients by 19F MAS NMR and factor analysis.
AB  - In this contribution the ability of (19)F MAS NMR spectroscopy to probe
      structural variability of poorly water-soluble drugs formulated as solid
      dispersions in polymer matrices is discussed. The application potentiality of the
      proposed approach is demonstrated on a moderately sized active pharmaceutical
      ingredient (API, Atorvastatin) exhibiting extensive polymorphism. In this
      respect, a range of model systems with the API incorporated in the matrix of
      polvinylpyrrolidone (PVP) was prepared. The extent of mixing of both components
      was determined by T(1)((1)H) and T(1rho)((1)H) relaxation experiments, and it was
      found that the API forms nanosized domains. Subsequently it was found out that
      the polymer matrix induces two kinds of changes in (19)F MAS NMR spectra. At
      first, this is a high-frequency shift reaching 2-3 ppm which is independent on
      molecular structure of the API and which results from the long-range polarization
      of the electron cloud around (19)F nucleus induced by electrostatic fields of the
      polymer matrix. At second, this is broadening of the signals and formation of
      shoulders reflecting changes in molecular arrangement of the API. To avoid
      misleading in the interpretation of the recorded (19)F MAS NMR spectra, because
      both the contributions act simultaneously, we applied chemometric approach based
      on multivariate analysis. It is demonstrated that factor analysis of the recorded
      spectra can separate both these spectral contributions, and the subtle structural
      differences in the molecular arrangement of the API in the nanosized domains can
      be traced. In this way (19)F MAS NMR spectra of both pure APIs and APIs in solid
      dispersions can be directly compared. The proposed strategy thus provides a
      powerful tool for the analysis of new formulations of fluorinated pharmaceutical
      substances in polymer matrices.

PMID- 22421444
TI  - Variants in follicle-stimulating hormone receptor gene in infertile Brazilian men
      and the correlation to FSH serum levels and sperm count.
AB  - The aim of the study was to analyze the distribution of the follicle-stimulating
      hormone (FSH) receptor (FSHR) Ala307Thr and Asn680Ser polymorphisms in infertile
      Brazilian men and evaluate the possible role of these polymorphisms on the serum
      levels of FSH and in sperm count. A case-control study was performed
      comprising138 infertile men with nonobstructive azoospermia (n = 53) or severe
      oligozoospermia (n = 85), and 217 fertile men as controls. Genotyping of FSHR
      polymorphisms was performed by real-time polymerase chain reaction (PCR). The
      results were analyzed statistically and a P value <.05 was considered
      significant. According to the sperm count, relatively similar FSHR polymorphisms
      genotype and allele frequencies were found among the groups, and combined
      genotypes of 2 polymorphisms did not identify a haplotype associated with sperm
      count. Considering FSH serum level according to genotypes of the Ala307Thr and
      Asn680Ser polymorphisms individually, statistical analysis showed no difference
      among the groups. When the combined genotypes of the FSHR polymorphisms were
      compared to FSH serum levels, no difference was also found among the groups. In
      conclusion, the findings demonstrate that, in Brazilian population studied,
      genetic variations, Asn680Ser and Thr307Ala, of the FSHR gene are not correlated
      with serum FSH levels or sperm count in male infertility.

PMID- 22421445
TI  - Pathogenic mechanisms linking periodontal diseases with adverse pregnancy
      outcomes.
AB  - In the last 2 decades, a large proportion of studies have focused on the
      relationship between maternal periodontal disease and poor obstetric outcomes.
      The aim of the present review is to summarize the current knowledge about human
      studies on the pathogenetic mechanisms linking periodontal diseases with adverse
      pregnancy outcomes. A search of the medical literature was conducted using NIH
      (National Institute of Health) Pubmed through April 2011. Articles were
      identified with the Medical Subject Heading (MeSH) and free text terms "small for
      gestational age (SGA)," "preeclampsia," "preterm labor," and "periodontal
      disease." Experimental human studies have shown that periodontal pathogens may
      disseminate toward placental and fetal tissues accompanied by an increase in
      inflammatory mediators in the placenta. As such, new inflammatory reactions
      within the placental tissues of the pregnant woman may occur, the physiological
      levels of prostaglandin E(2) (PGE(2)) and tumor necrosis factor-alpha (TNF-alpha)
      in the amniotic fluid may increase and eventually lead to premature delivery.
      Although many data from clinical trials suggest that periodontal disease may
      increase the adverse pregnancy outcome, the exact pathogenetic mechanism involved
      remains controversial. The findings explain the potential link between
      periodontal infections and adverse pregnancy outcomes. First, periodontal
      bacteria can directly cause infections both of the uteroplacenta and the fetus;
      second, systemic inflammatory changes induced by periodontal diseases can
      activate responses at the maternal-fetal interface. Of note, associative studies
      have produced different results in different population groups and no conclusive
      evidence has still been produced for the potential role of preventive periodontal
      care to reduce the risk factors of preterm birth.

PMID- 22421446
TI  - Mid-gestation ovine cardiomyocytes are vulnerable to mitotic suppression by
      thyroid hormone.
AB  - Circulating fetal 3,3',5-tri-iodo-l-thyronine (T(3) ) is maintained at very low
      levels until a dramatic prepartum surge. 3,3',5-Tri-iodo-l-thyronine inhibits
      serum-stimulated proliferation in near-term ovine cardiomyocytes, but it is not
      known whether midgestation myocytes are also inhibited. Because early cessation
      of cardiomyocyte mitosis would result in an underendowed heart, we hypothesized
      that 0.67 gestation (100 of 145 days gestation) ovine cardiomyocytes would be
      insensitive to suppressive growth effects of T(3) . These younger cardiomyocytes
      were grown with T(3) in 10% serum-enriched media for 24 hours. Physiological
      (0.37, 0.75, and 1.5 nmol/L) concentrations of T(3) dramatically suppressed
      mitotic activity in cardiomyocytes (P < .001). 3,3',5-Tri-iodo-l-thyronine
      stimulated phosphorylation of extracellular signal-regulated kinase and AKT (also
      known as Protein Kinase B [PKB]) signaling pathways. Nevertheless, the protein
      content of the cell cycle suppressor, p21, increased 2-fold (P < .05), and
      promoter, cyclin D1, decreased by 50%. Contrary to our hypothesis, elevated
      levels of T(3) powerfully inhibit proliferation of midgestation fetal
      cardiomyocytes. Thus, midgestation maternal hyperthyroidism might lead to an
      underendowed fetal myocardium.

PMID- 22421447
TI  - Influence of HPV16 E6/7 on the expression of FGF2 and FGFR type B in cervical
      carcinogenesis.
AB  - This study investigates the influence of fibroblast growth factor receptor type B
      (FGFRb) and fibroblast growth factor on cervical carcinogenesis associated with
      HPV16 E6/7 infection, using primary cancer cells isolated from Taiwanese patients
      with cervical cancer. Functional interaction between FGFRb in Cx cells and HPV16
      E6/7 transfected Cx cells (CxWJ cells) following treatment with FGF-7, according
      to cell growth, invasive ability, and tumor growth in SCID mice. Our results
      indicate that the downregulation of FGFRb gene expression in CxWJ cells partially
      represses proliferation and the invasive ability provided by FGF-7 stimulation.
      In SCID mice, the FGF2 and FGFR1 gene expression ascend in CxWJ tumor nodule.
      These data provide evidence of a functional interaction between HPV16 E6/7 in
      FGFRb and FGF2, suggesting that cooperative stimulation of HPV E6/7 in
      inactivated FGFRb and the upregulation of FGF2 may be necessary to completely
      overcome the oncogenic function associated with the progression of cervical
      carcinogenesis.

PMID- 22421448
TI  - Changes in fetal thymic immune cell populations in a sheep model of intrauterine
      inflammation.
AB  - Intrauterine inflammation is a common antecedent of preterm birth and can alter
      the development of the fetal thymus, the site of development, and maturation of T
      lymphocytes. The effects of intrauterine inflammation on specific thymic T
      lymphocyte populations are largely unknown. We hypothesized that intrauterine
      inflammation would alter fetal thymic T cell populations. Immunohistochemistry
      was used to quantitate the relative proportions of thymic cortical and medullary
      cell populations in fetal sheep 7 days after intra-amniotic lipopolysaccharide
      (LPS) injection. The proportions of CD8+and MHC II+ cells in the fetal thymus
      were reduced in response to LPS. The ratio of CD4:CD8 cells was increased by LPS
      exposure. No changes were observed in the percentage of CD4+, gammadelta(WC1)+,
      CD45R+B cells, or CD44+ cells. These studies indicate that intrauterine
      inflammation impacts thymic composition of CD8 T cells and the development and/or
      activation of CD4 T cells in the fetal thymus.

PMID- 22421449
TI  - Administration of the PARP inhibitor Pj34 ameliorates the impaired vascular
      function associated with eNOS(-/-) mice.
AB  - A low-resistance/high-flow uteroplacental circulation is integral to a healthy
      pregnancy. Impaired flow in the uterine circulation is associated with
      intrauterine growth restriction (IUGR) and preeclampsia (PE). Poly(ADP-ribose)
      polymerase (PARP) is a nuclear enzyme which has been associated with oxidative
      stress-induced vascular dysfunction. Using the endothelial nitric oxide synthase
      (eNOS(-/ -)) knockout mouse model, which features vascular dysfunction and IUGR,
      we tested the hypothesis that administration of a PARP inhibitor may ameliorate
      the vascular dysfunction associated with the eNOS(-/-) model. eNOS(-/-) animals
      were characterized by impaired uterine artery function when compared to controls.
      Administration of the PARP inhibitor PJ34 prevented this dysfunction. Gestational
      day (GD) 17.5 eNOS(-/-) mice did not exhibit altered systolic blood pressure when
      compared to control mice. However, treatment of eNOS(-/-) mice with PJ34
      significantly reduced systolic blood pressure when compared to vehicle-treated
      eNOS(-/-). Administration of a PARP inhibitor protects uterine artery function in
      the face of eNOS(-/-) deficiency.

PMID- 22421450
TI  - Neuraminidase inhibitors for treatment of equine influenza - when all else fails?

PMID- 22421451
TI  - Genotoxic potential of arsenic at its reference dose.
AB  - Arsenic, a highly hazardous contaminant in our drinking water, accounts for
      various toxic effects (including cancer) in human. However, intake of arsenic
      @0.3 MUg kg(-1)day(-1) through drinking water, containing arsenic at its
      guideline value or maximum contaminant limit (10 MUg L(-1)), has been estimated
      to pose very little or no measurable risk to cancer in humans. The value also
      appears to be equal to the human reference dose (or index dose) of arsenic based
      on human skin toxicity data. The present work was a quantitative assessment of
      the genotoxic potential of arsenic in mice at doses equivalent to its human
      reference dose as well as its multiples. Significant increases in the frequencies
      of chromosome abnormalities in the bone marrow cells were registered over the
      control level upon exposure to all the doses of arsenic including its reference
      dose (or index dose). The assessment of arsenic genotoxicity in humans at low
      doses will therefore be highly instrumental in establishing a permissible limit
      of arsenic in drinking water.

PMID- 22421452
TI  - Associations between circulating levels of bisphenol A and phthalate metabolites
      and coronary risk in the elderly.
AB  - Studies have pointed out associations between various chemicals with estrogenic
      activity and cardiovascular disease. Being ubiquitous, the plastic additive
      substances bisphenol A (BPA), and phthalates have been detected in almost all
      types of analyzed human samples. The aim of this study was to investigate whether
      circulating levels of BPA and/or four selected phthalate metabolites are
      associated to coronary risk in an elderly population. In the Prospective
      Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, coronary risk
      was assessed by the Framingham Risk Score (FRS) together with circulating serum
      levels of BPA and the four phthalate metabolites monoisobutyl phthalate (MiBP),
      monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-(2-ethylhexyl)
      phthalate (MEHP) in 1016 subjects aged 70 years. BPA, MEHP, and MMP were
      associated to LDL-cholesterol and MEHP to HDL-cholesterol, MEP to diastolic blood
      pressure and MiBP to fasting glucose when the compounds were investigated one by
      one. After Bonferronni correction, only the relations for MMP to LDL-cholesterol
      (p<0.0001), MEP to diastolic blood pressure (p<0.0002), and MiBP to fasting
      glucose (p<0.0001) remained significant. MMP was associated to the FRS (p=0.02),
      but after Bonferronni correction, this association was not significant. In
      conclusion, associations were found between MMP and LDL-cholesterol, MEP and
      diastolic blood pressure, and MiBP and fasting glucose. We did not observe any
      strong associations between BPA nor any of the four phthalate metabolites and
      Framingham Risk Score in this elderly population.

PMID- 22421453
TI  - Antioxidant enzyme activities as biomarkers of Zn pollution in fluvial biofilms.
AB  - The potential of the antioxidant enzyme catalase (CAT) and ascorbate peroxidase
      (APX) as molecular biomarkers of Zn toxicity in freshwater biofilms has been
      explored in this study jointly with other classical functional and structural
      endpoints (photosynthetic parameters, algal group composition and
      bioaccumulation). Biofilms were colonized in an indoor microcosm system for 5
      weeks and then exposed to Zn for 5 weeks. To evaluate Zn effects, biofilms were
      sampled 5 and 3 days before exposure, just before exposure (time 0), and after
      6h, 1, 3, 7, 21 and 35 days of metal exposure. Most endpoints measured were
      affected by Zn exposure (320 MUg Zn L(-1)) during both periods of exposure. APX
      was the only functional parameter responding after a few hours of Zn exposure,
      highlighting its use as an early toxicity biomarker. Structural changes began
      after 3 days of exposure, starting with a decrease in algal biomass and an
      increase in the OD 430:665 ratio. Structural changes in biofilm communities were
      observed after 1 week, leading to a shift from diatoms to cyanobacteria and green
      algae-dominated communities. CAT activity was thereafter enhanced (after three
      weeks of exposure) and attributed not only to a direct effect of Zn
      bioaccumulation but also to an indirect effect of the community composition
      changes driven by chronic metal exposure. It can be concluded that biofilm
      antioxidant enzyme activities may provide evidence of early stress caused by
      metal exposure and also provide information about the mechanism of community
      adaptation. This information can be of great interest to improve current tools
      used for risk assessment.

PMID- 22421454
TI  - Exogenous nitric oxide donor protects Artemisia annua from oxidative stress
      generated by boron and aluminium toxicity.
AB  - Nitric oxide (NO) is an important signal molecule modulating the response of
      plants to environmental stress. Here we report the effects of boron (B) and
      aluminium (Al) contamination in soil, carried out with or without application of
      exogenous SNP (NO donor), on various plant processes in Artemisia annua,
      including changes in artemisinin content. The addition of B or Al to soil medium
      significantly reduced the yield and growth of plants and lowered the values of
      net photosynthetic rate, stomatal conductance, internal CO(2) concentration and
      total chlorophyll content. The follow-up treatment of NO donor favoured growth
      and improved the photosynthetic efficiency in stressed as well as non-stressed
      plants. Artemisinin content was enhanced by 24.6% and 43.8% at 1mmole of soil
      applied B or Al. When SNP was applied at 2mmole concentration together with
      either 1mmole of B and/or Al, it further stimulated artemisinin biosynthesis
      compared to the control. Application of B+Al+SNP proved to be the best treatment
      combination for the artemisinin content in Artemisia annua leaves.

PMID- 22421455
TI  - Cushing's disease as a cause of severe osteoporosis: a clinical challenge.
AB  - Secondary osteoporosis is a frequently underestimated bone disorder. It is a
      secondary cause of bone loss that affects more than half of men and premenopausal
      and perimenopausal women, and about one-fitfth of postmenopausal women. We herein
      report an uncommon case of multiple fractures due to secondary osteoporosis
      caused by Cushing's disease. In this case the appearance of fractures in a 41
      years old woman was the sign of alarm that ultimately lead us to the diagnosis.

PMID- 22421456
TI  - Cost-utility and budget impact analysis of primary prevention with alendronate of
      osteoporotic hip fractures in Catalonia.
AB  - OBJECTIVES: To determine whether primary drug prevention of osteoporotic hip
      fracture is a useful measure in Catalonia and what would be their budgetary
      impact. MATERIAL AND METHODS: We performed a cost-utility social perspective
      study with a time horizon of 10 to 20 years. Univariate sensitivity analysis was
      performed. Doing nothing is compared with an intervention that includes screening
      for osteoporosis in women> 64 years and in those diagnosed and who received
      treatment with generic alendronate for 10 years. Decision trees are developed for
      groups of 65-69, 70-74 and 75-79. HF data is from 2009 hospital discharges .Costs
      are derived from fees paid by public insurance. RESULTS: In 2009 there were 9262
      HF. The direct cost was ? 55 million (? 5,943.4/patient). The total cost was ?
      227 million for 10 years. The intervention dominates in all age groups in a 20
      year perspective. In any horizon and age group, the different scenario puts the
      value per QALY below or within the proposed values for Spain. The budgetary
      impact is estimated at ? 8.9 million which increased by 31% the actual direct
      cost, and 0.5% of the public pharmacy budget. Considering the total costs and the
      prospect of 20 years, annual savings of 7.4 million ? were seen. CONCLUSIONS: The
      prevention of HF with alendronate in osteoporotic women>64 years is cost-useful
      in the long term (20 years) with a low budgetary impact in the 75-79 year group.

PMID- 22421457
TI  - [New therapeutic targets in psoriatic arthritis].
AB  - Registries estimate that one third of patients with psoriatic arthritis (PsA) are
      "resistant" to of TNF-alpha blockers. Therefore, the search for new approaches to
      treatment of this disease may be justified. Currently the treatment options that
      have proven effective are associated with inhibition of the T cell costimulatory
      pathway (abatacept and alefacept) and blocking the P40 fraction of IL-12 and IL
      23 (ustekinumab). A novel pathway inhibition, which deserves special attention is
      offered by apremilast. This molecule inhibits phosphodiesterase IV, responsible
      for hydrolyzing cyclic adenosine monophosphate to adenosine monophosphate, which
      causes an increase in cAMP. This metabolite is associated with decreased TNF
      alpha. It has a modest efficacy (ACR 20 response of 43%), and subsequent studies
      have shown an improvement in visual analog scale and the SF36 compared to
      placebo. Currently there are five clinical trials in phase III to assess its
      effectiveness in parameters of inflammation and radiographic progression. The
      spectrum of possibilities before treatment failure with anti-TNF alpha, is
      augmented by the appearance of several reports that show efficacy with the
      individual use of CD20 inhibitors and IL-1. In patients with rheumatoid arthritis
      (RA) the effectiveness of molecules that inhibit signal transduction of cytokines
      (Anti-JAK) has been proven, so it is possible that in the future they may be used
      in patients with PsA.

PMID- 22421458
TI  - [Diagnosis and treatment of Chlamydia-induced reactive arthritis].
AB  - Urogenital chlamydia infections are the most prevalent of all sexually
      transmitted diseases although the number of chlamydia-induced reactive arthritis
      cases are generally below the estimated incidence of the disease. This may be
      related with the high rate of asymptomatic chlamydial infections and the lack of
      adequate diagnostic criteria. Polymerase chain reaction (PCR), a new system for
      detection of Chlamydia, is one of the most useful techniques for the diagnosis of
      this disease. Biologic therapy produces theoretical doubts regarding its
      indication and there is little information related with chlamydia induced
      reactive arthritis treatment efficacy. Although the usefulness of long antibiotic
      treatment is not clear, the use of combination antibiotics opens new therapeutic
      strategies for chlamydia induced reactive arthritis.

PMID- 22421459
TI  - Mixed-norm estimates for the M/EEG inverse problem using accelerated gradient
      methods.
AB  - Magneto- and electroencephalography (M/EEG) measure the electromagnetic fields
      produced by the neural electrical currents. Given a conductor model for the head,
      and the distribution of source currents in the brain, Maxwell's equations allow
      one to compute the ensuing M/EEG signals. Given the actual M/EEG measurements and
      the solution of this forward problem, one can localize, in space and in time, the
      brain regions that have produced the recorded data. However, due to the physics
      of the problem, the limited number of sensors compared to the number of possible
      source locations, and measurement noise, this inverse problem is ill-posed.
      Consequently, additional constraints are needed. Classical inverse solvers, often
      called minimum norm estimates (MNE), promote source estimates with a small l2
      norm. Here, we consider a more general class of priors based on mixed norms. Such
      norms have the ability to structure the prior in order to incorporate some
      additional assumptions about the sources. We refer to such solvers as mixed-norm
      estimates (MxNE). In the context of M/EEG, MxNE can promote spatially focal
      sources with smooth temporal estimates with a two-level l1/l2 mixed-norm, while a
      three-level mixed-norm can be used to promote spatially non-overlapping sources
      between different experimental conditions. In order to efficiently solve the
      optimization problems of MxNE, we introduce fast first-order iterative schemes
      that for the l1/l2 norm give solutions in a few seconds making such a prior as
      convenient as the simple MNE. Furthermore, thanks to the convexity of the
      optimization problem, we can provide optimality conditions that guarantee global
      convergence. The utility of the methods is demonstrated both with simulations and
      experimental MEG data.

PMID- 22421460
TI  - Do socio-economic, behavioural and biological risk factors explain the poor
      health profile of the UK's sickest city?
AB  - BACKGROUND: The extent to which the poor health profile of Glasgow, the city with
      the highest mortality rates in the UK, can be explained solely by socio-economic
      factors is unclear. This paper additionally considers behavioural and biological
      factors as explanations of excess risk. METHODS: Scottish Health Survey data for
      2008-09 were analysed using logistic regression models to compare the odds of
      physical and mental health outcomes, as well as adverse health behaviours, for
      residents of the Greater Glasgow and Clyde (GGC) conurbation compared with the
      rest of Scotland. RESULTS: After adjustment for age and sex, significant
      differences were observed among Glasgow residents for most mental and physical
      health outcomes, but not for most adverse health behaviours. Adjustment for area
      and individual-level socio-economic characteristics explained the differences for
      all outcomes except anxiety, psychological ill-health, heart attack and men being
      overweight. After additional adjustment for behavioural and biological
      characteristics, significantly higher odds of anxiety and heart attack remained
      for residents of the Glasgow area. CONCLUSIONS: Adjusting for area- and
      individual-level socio-economic conditions explained the excess risk associated
      with residents of GGC for most (16 out of 18) outcomes; however, significant
      excess risks for two outcomes remained: anxiety and heart attack. Additional
      explanations are, therefore, required.

PMID- 22421461
TI  - Inequalities, migration and ethnicity Comment on Dr Raj S. Bhopal's Research
      agenda for tackling inequalities related to migration and ethnicity in Europe.

PMID- 22421462
TI  - Antibiotic-loaded polymethylmethacrylate beads for the treatment of extracavitary
      vascular surgical site infections.
AB  - OBJECTIVE: This study assessed the efficacy of antibiotic-loaded
      polymethylmethacrylate (PMMA) beads in the treatment of lower extremity vascular
      surgical site infections (VSSIs). METHODS: This was a retrospective review of all
      patients with a VSSI of a lower extremity bypass treated with antibiotic-loaded
      PMMA beads and culture-specific antibiotics during a 4.5-year period. Data
      collected included patient demographics, comorbidities, site of initial graft
      infection, symptoms and signs at presentation, initial and additional surgical
      debridement, wound culture results, type of antibiotic beads implanted, and graft
      treatment strategy, comprising conduit preservation or in situ replacement, with
      associated soft tissue management by muscle flap or vacuum-assisted closure.
      Primary outcome measures included death, recurrent infection, and limb salvage.
      RESULTS: Forty patients developed 42 extracavitary lower extremity VSSIs
      (bilateral groin infections in two). Patients were treated according to our
      treatment algorithm with antibiotic-impregnated PMMA beads. Previous
      reconstructions included nine aortofemoral bypasses (groin infection only), 20
      infrainguinal bypasses, five extra-anatomic bypasses, five femoral
      interpositions, two combined inflow-outflow bypass procedures, and one patch
      angioplasty with VSSI. Cultures isolated 59 pathogens (39 gram-positive, 18 gram
      negative, 2 Candida spp). Methicillin-resistant Staphylococcus aureus was
      cultured from 10 VSSs (23.8%) overall and from 27.7% of those patients with
      attempted graft preservation or in situ reconstructions. Two patients (4.8%) had
      no growth despite clinical signs of infection. Repeat VSS exploration and culture
      results led to an average of 1.4 bead replacements before definitive treatment.
      Final treatment strategy included graft preservation of patent bypasses in 28,
      partial graft excision with in situ replacement in eight, graft removal only with
      residual graft remaining at implant site (ie, incorporated anastomotic conduit,
      11.9%) in five, and extra-anatomic reconstruction in one. Sartorius muscle flap
      was performed in 14 groin infections (37.8%). The 30-day mortality was 0%, and
      limb loss was 7.1% (n = 3). At the median follow-up of 17 months, the limb loss
      was 21.4% and the recurrent infection rate was 19.4% (seven of 36) in those with
      attempted graft preservation or in situ replacement. CONCLUSIONS: Antibiotic
      loaded PMMA beads may serve as an adjunct in the management of VSSIs and may also
      expand treatment options for graft preservation or in situ reconstruction, with
      expected recurrent infection rate approaching 20%. Further experience with this
      adjunct may help elucidate its role in the management of this complicated
      problem, including the need for bead exchanges, until perigraft cultures are free
      of microbes.

PMID- 22421463
TI  - Carbohydrate supplementation increases intramyocellular lipid stores in elite
      runners.
AB  - The objective was to determine the effects of carbohydrate (CHO) supplementation
      on exercise-induced hormone responses and post-training intramyocellular lipid
      stores (IMCL). Twenty-four elite male athletes (28.0+/-1.2 years) were randomized
      to receive CHO (maltodextrin solution) or zero energy placebo solution (control
      group). The high-intensity running protocol consisted of 10*800 m at 100% of the
      best 3000-m speed (Vm3 km) and 2*1000 m maximal bouts in the morning and a
      submaximal 10-km continuous easy running in the afternoon of day 9. IMCL
      concentrations were assessed by (1)H-MRS before (-day 9) and after training (day
      9) in soleus (SO) and tibialis anterior (TA) muscles. Blood hormones were also
      measured before, during, and post-exercise. The percent change (Delta%) in TA
      IMCL was higher in the CHO group (47.9+/-24.5 IMCL/Cr) than in the control group
      (-1.7+/-13.1, respectively) (P=.04). Insulin concentrations were higher in the
      CHO group post-intermittent running compared to control (P=.02). Circulating
      levels of free fatty acids and GH were lower in the CHO group (P>.01). The
      decline in performance in the 2nd 1000-m bout was also attenuated in this group
      compared to control (P<.001 and P=.0035, respectively). The hormonal milieu
      (higher insulin and lower GH levels) in the CHO group, together with unchanged
      free fatty acid levels, probably contributed to the increased IMCL stores. This
      greater energy storage capacity may have improved post-exercise recovery and thus
      prevented performance deterioration.

PMID- 22421464
TI  - An SYBR Green-based real-time RT-PCR assay for the detection of H5 hemagglutinin
      subtype avian influenza virus.
AB  - Increasing diversity among H5 hemagglutinin (HA) subtype avian influenza (AI)
      viruses has resulted in the need of novel sensitive and specific molecular
      assays. In this study, an SYBR Green-based real-time reverse transcription-PCR
      (RRT-PCR) assay was developed for the detection of H5 subtype AI virus. Sequence
      analysis of the Mexican lineage H5N2 isolates (subgroup B) revealed several
      mismatches in the primer/hydrolysis probe set reported in the commonly used RRT
      PCR assay for the detection of H5 North American lineage. The present assay was
      designed to circumvent the challenge that these viruses represent for the
      specific detection of H5 subtype AI viruses. This RRT-PCR assay successfully
      detected a range of different H5 subtype AI strains from both Eurasian and North
      American lineages representing different avian H5 HA clades from diverse
      geographical locations. The sensitivity of the present method was determined by
      using in vitro-transcribed RNA and 10-fold serial dilutions of titrated AI
      viruses. High sensitivity levels were obtained, with limits of detection of 10(0)
      50% egg infectious dose (EID50)/mL and 4.2 gene copies/MUl. The linear ranges of
      the assay span within 10(6)-10(0) EID50/mL and 10(6)-10(0) gene copies/MUl. The
      results obtained from this method were directly compared with those of the H5 RRT
      PCR assay recommended by the OIE. The comparison was performed with 110 tracheal
      and cloacal swabs from various bird species collected during field and laboratory
      investigations in Eurasia and Africa in 2006 and 2008 and showed 100% agreement.
      This assay is recommended as an alternative method, also allowing a 'double
      check' approach detection, to be use mainly in outbreak scenarios with higher
      risk of poultry infections by Central American/Caribbean H5 AI viruses.

PMID- 22421465
TI  - Voice characteristics before versus after mandibular setback surgery in patients
      with mandibular prognathism using nonlinear dynamics and conventional acoustic
      analyses.
AB  - OBJECTIVES: The purpose of this study was to explore the voice characteristics of
      patients with mandibular prognathism, and to investigate the effects of
      mandibular setback surgery on these characteristics using nonlinear dynamics and
      conventional acoustic analyses. MATERIALS AND METHODS: Sixteen patients (8 males
      and 8 females) who had skeletal 3, class III malocclusion without cleft palate,
      and who underwent a bilateral sagittal split ramus osteotomy (BSSRO), were
      enrolled. As controls, 50 healthy adults (25 males and 25 females) were enrolled.
      The mean first LEs (mLE1) computed for each one-second interval, and the
      fundamental frequency (F0) and frequencies of the first and second formant (F1,
      F2) were calculated for each Japanese vowel. RESULTS AND CONCLUSIONS: The mLE1s
      for /u/ in males, and /o/ in females and the F2s for /i/ and /u/ in males,
      changed significantly after BSSRO. Class III voice characteristics were observed
      in the mLE1s for /i/ in both males and females, in the F0 for /a/, /i/, /u/ and
      /o/ in females, and in the F1 and F2 for /a/ in males, and the F1 for /u/ and the
      F2 for /i/ in females. Most of these characteristics were preserved after BSSRO.

PMID- 22421466
TI  - Isolation and characterization of multipotent postnatal stem/progenitor cells
      from human alveolar bone proper.
AB  - In the search for an ideal minimally-invasive multipotent postnatal stem cells'
      source, the aim of the present study was to isolate and characterize multipotent
      postnatal stem/progenitor cells from the human alveolar bone proper tissue of the
      oral cavity. Cells were isolated from human alveolar bone parts,
      immunomagnetically sorted using STRO-1 antibodies and characterized flow
      cytometrically for the expression of CD14, CD34, CD45, CD73, CD90, CD105,
      CD146/MUC18 and STRO-1 surface markers. Colony-formation and multilineage
      differentiation potential were tested. Mineralized tissue marker expression was
      examined using real time polymerase chain reaction (PCR). The cells were plastic
      adherent and showed colony-formation. Cells expressed the surface markers CD73,
      CD90, CD105, STRO-1 and CD146/MUC18, while lacking the expression of the
      hematopoietic markers CD14, CD34 and CD45. Cells could be differentiated into
      osteoblastic, adipocytic and chondroblastic lineages. Unstimulated cells
      expressed alkaline phosphatase (ALP), type I, III and V collagens, osteonectin
      and osteocalcin in a very distinctive pattern. This study presents a practical
      and minimally-invasive scheme for the isolation of multipotent postnatal
      stem/progenitor cells from the human alveolar bone tissue of the oral cavity.

PMID- 22421467
TI  - Use of gas combination cryosurgery for treating ameloblastomas of the jaw.
AB  - This study evaluated the results of curettage followed by spray propane, butane,
      and isobutane gas combination cryosurgery in 10 patients with ameloblastoma. The
      patients' age ranged from 7 to 87 years (mean, 31 years), with equal prevalence
      in both men and women. Five cases were diagnosed as solid ameloblastomas and 5 as
      unicystic ameloblastomas. Before enucleation and cryosurgery, the unicystic
      lesions received marsupialisation to decrease their size. No patient showed
      evidence of clinical or radiographic recurrence, pathologic fracture, or
      infection after treatment with enucleation and cryosurgery. The most common
      complication was wound dehiscence, which was observed in all cases. The average
      follow-up period was 60.5 months (range 48-108 months). These results show that
      enucleation followed by cryosurgery is an effective therapy for managing
      ameloblastomas.

PMID- 22421468
TI  - Evaluation of nasal reconstruction procedures results.
AB  - Before undergoing a reconstructive procedures of the nose most patients ask how
      they will look postoperatively. Anthropometric measurements of the nose described
      by Farkas represent standard values. A comparison of pre- and postoperative
      anthropometric measurements may help to double-check the correctness of
      intraoperative "eye-balling" measurements with regards to postoperative
      appearance. Sixty-three patients underwent reconstruction of nasal ala, tip or
      dorsum. An analysis of standardized pre- and postoperative photographs included
      measurements of nose width, nose height, nasal tip protrusion, columella width,
      ala length, intercanthal width, mouth width, philtrum width, upper lip height,
      lateral upper lip height, cutaneous upper lip height and upper face height.
      Preoperative measurements were compared to data given by Farkas in young adults.
      Postoperative changes were evaluated clearly distinguishing between
      reconstruction of nasal ala, tip and dorsum. All anthropometric indices showed
      significant differences compared to the Farkas population. There was no
      significant pre- to postoperative change in any reconstructed region observed,
      indicating adequate intraoperative measurements. The application of Farkas'
      anthropometric measurements described in this study showed reliable and objective
      results and can help to double-check the previous intraoperative measurements.
      The correct application of these surgical techniques leads to a satisfying and
      near to normal postoperative look of the patient.

PMID- 22421469
TI  - Use of intermaxillary forces in early treatment of maxillary deficient class III
      patients: results of a case series.
AB  - INTRODUCTION: The early treatment of Class III malocclusion with a protraction
      facemask can produce forward movement of the maxilla but is generally associated
      with posterior rotation of the mandible and dentoalveolar compensations. This
      article shows the dental and skeletal effects of intermaxillary elastics applied
      to temporary anchorage devices in the treatment of maxillary deficient Class III
      patients. MATERIALS AND METHODS: A total of 6 patients with skeletal Class III
      malocclusion were treated with intermaxillary elastics only. This traction was
      applied between modified miniplates placed in the maxilla and a modified lower
      acrylic resin plate bonded on mandibular tooth surfaces. To evaluate the
      orthodontic changes, lateral cephalograms were taken at the start of the
      treatment (T1), at the end of the orthopaedic treatment (T2) and at the follow-up
      (T3). RESULTS: All patients showed orthopaedic correction of the skeletal Class
      III relationship with reduction of facial concavity. No dentoalveolar
      compensations or changes in mandibular position were observed. CONCLUSION: The
      treatment of maxillary deficiency with orthopaedic forces from skeletal anchorage
      directed to the hooks of a modified lower acrylic resin plate bonded on the
      mandibular tooth surfaces, seems to be a promising technique.

PMID- 22421470
TI  - Comparative analysis of preemptive analgesic effect of tramadol chlorhydrate and
      nimesulide following third molar surgery.
AB  - The aim of this prospective, randomized, controlled, paired trial was to perform
      a comparative analysis of the preemptive analgesic effect of nimesulide and
      tramadol chlorhydrate during third molar surgery. The study was carried out
      between March and November 2009, involving 94 operations in 47 male and female
      patients with bilateral impacted lower third molars in comparable positions. The
      sample was divided into two groups. Group A received an oral dose of 100 mg of
      nimesulide 1 h prior to surgery. Group B received an oral dose of 100 mg of
      tramadol chlorhydrate 1 h prior to surgery. The following aspects were evaluated
      in the postoperative period: adverse effects of the drugs; amount of rescue
      medication used (acetaminophen 750 mg); and pain 5, 6, 24, 36, 48, 60, 72 and 84
      h after surgery using a visual analog pain scale. Peak pain occurred 5 h after
      surgery in both groups, with a mean pain score of 2.3 in Group A and 3.0 in Group
      B; this difference did not achieve statistical significance (p > 0.141). Based on
      the sample studied, nimesulide and tramadol chlorhydrate demonstrate similar
      preemptive analgesic effects when used in lower third molar surgeries.

PMID- 22421471
TI  - Mirror, mirror on the wall...: self-perception of facial beauty versus judgement
      by others.
AB  - In 1878, Margaret Wolfe Hungerford published a simple but insightful phrase in
      her novel 'Molly Bawn' that was to be quoted so often it has almost become
      cliche: "Beauty is in the eye of the beholder". While many questions regarding
      the perception and neural processing of facial attractiveness have been resolved,
      it became obvious to us that study designs have been principally based on either
      facial self-perception or perception by others. The relationship between these
      however, remains both crucial and unknown. Standardized images were taken of 141
      subjects. These 141 subjects were asked to complete the adjective mood scale
      (AMS) and to rank specific issues related to their looks on a visual analogue
      scale. The images were then shown to independent judges to rank specific issues
      related to their looks on a visual analogue scale. Our results show proof for a
      strikingly simple observation: that individuals perceive their own beauty to be
      greater than that expressed in the opinions of others (p < 0.001). This
      observation provides insight into our basic behavioural patterns and suggests
      that there are strong psychological mechanisms in humans supporting self
      identification and thereby encouraging the self-confidence and resilience
      necessary to maintain one's social standing. While the psychological basis of
      self-confidence is multifactorial, our finding provides critical objective
      insight. We prove here for the first time that nothing more than the beauty of
      the beholder is in the eyes of the latter.

PMID- 22421473
TI  - Mondor's thrombophlebitis 13 years after breast augmentation.
AB  - PATIENT: A 37-year-old woman presented with Mondor's thrombophlebitis 13 years
      after augmentation mammaplasty with subpectoral saline implants. She presented
      complaining of 1 week of "band-like" cords and pain involving the
      thoracoepigastric and lateral thoracic vessels. She was evaluated and ruled out
      for other etiologies of her breast symptoms. BACKGROUND: Mondor's disease is a
      benign and self-limiting disease characterized by thrombophlebitis of the
      subcutaneous veins of the chest and abdominal wall. The inflammation causes
      painful superficial cords manifesting as skin retraction. Mondor's disease has
      been described in aesthetic breast surgery literature, but most cases occur
      within the first few postoperative weeks. CONCLUSIONS: Mondor's disease may be
      idiopathic, iatrogenic, or a manifestation of underlying pathology such as breast
      cancer. The diagnosis of iatrogenic Mondor's disease can be made with high
      clinical certainty when following aesthetic breast surgery in the early
      postoperative period. However, in late presentations that are not immediately
      related to surgery, Mondor's disease remains a diagnosis of exclusion, and other
      underlying pathologic etiologies must be ruled out.

PMID- 22421474
TI  - Use of fetal bovine acellular dermal xenograft with tissue expansion for staged
      breast reconstruction.
AB  - INTRODUCTION: Staged breast reconstruction with implants and human acellular
      cadaveric dermis offers advantages of precise expander positioning, higher
      initial expander fill volumes, and improved outcomes. This study reports breast
      reconstruction using fetal bovine acellular dermal matrix (FBADM). The high type
      III collagen content of FBADM may allow for more rapid tissue incorporation and
      healing. METHODS: A total of 49 breast reconstructions in 28 patients (group A)
      with FBADM were retrospectively compared with 123 reconstructions in 91 patients
      operated without FBADM (group B). RESULTS: FBADM sizes ranged from 48 to 100 cm2
      (mean size: 70.6 cm2). The mean immediate fill volume in group A was 181.2 +/-
      148.3 mL and 117.7 +/- 66.3 mL in group B (P < 0.001). The duration of drainage
      was significantly shorter in group A (8.51 +/- 3.4 days) as compared with
      controls (11.07 +/- 5.1 days), t-test (P = 0.015). There was no significant
      difference in the overall complication rate (20.8% in group A, 13.0% in group B).
      Further subgroup analysis of group A patients with complications and without
      complications, showed that group with complications had significantly longer
      drain removal time (9.48 vs. 7.97 days), larger initial fill volumes (238.1 vs.
      145.3 mL), and a higher BMI (25.8 vs. 22.6 kg/m2) when compared with the
      complication-free subgroup. CONCLUSIONS: The use of FBADM in breast
      reconstruction offers results comparable with that of human acellular dermal
      matrix as reported in the literature. However, FBADM significantly reduced wound
      drainage time in our study when compared with patients without FBADM.

PMID- 22421475
TI  - Supercharged free fibula for complex ankle arthrodesis: a case report.
AB  - We report the successful use of a supercharged free fibula for tibial
      reconstruction and ankle arthrodesis. A 28-year-old woman underwent resection of
      a giant cell tumor of the distal tibia and reconstruction using a methyl
      methacrylate cement spacer 12 years prior. The spacer eroded into her ankle joint
      causing significant pain with ambulation. Therefore, she required ankle
      arthrodesis but lacked distal tibia bone stock. The ipsilateral fibula was
      harvested for reconstruction and transferred on its distal blood supply into the
      bony tibial defect. The proximal blood supply of the fibula flap was then
      anastomosed to the posterior tibial vessels to supercharge the blood supply. An
      Ilizarov was placed for external fixation. The combination of a supercharged free
      fibula and stable external fixation for tibial reconstruction led to timely bony
      union and ambulation, as well as avoiding the potential complications that can
      occur with other reconstructive options.

PMID- 22421476
TI  - A systematic review and meta-analysis of complications associated with acellular
      dermal matrix-assisted breast reconstruction.
AB  - BACKGROUND: Multiple outcome studies have been published on the use of acellular
      dermal matrix (ADM) in breast reconstruction with disparate results. The purpose
      of this study was to conduct a systematic review and meta-analysis to determine
      an aggregate estimate of risks associated with ADM-assisted breast
      reconstruction. METHODS: The MEDLINE, Web of Science, and Cochrane Library
      databases were queried, and relevant articles published up to September 2010 were
      analyzed based on specific inclusion criteria. Seven complications were studied
      including seroma, cellulitis, infection, hematoma, skin flap necrosis, capsular
      contracture, and reconstructive failure. A pooled random effects estimate for
      each complication and 95% confidence intervals (CI) were derived. For comparisons
      of ADM and non-ADM, the pooled random effects odds ratio (OR) and 95% CI were
      derived. Heterogeneity was measured using the I2 statistic. RESULTS: Sixteen
      studies met the inclusion criteria. The pooled complication rates were seroma
      (6.9%; 95% CI, 5.3%-8.8%), cellulitis (2.0%; 95% CI, 1.2%-3.1%), infection (5.7%;
      95% CI, 4.3%-7.3%), skin flap necrosis (10.9%; 95% CI, 8.7%-13.5%), hematoma
      (1.3%; 95% CI, 0.6%-2.4%), capsular contracture (0.6%; 95% CI, 0.1%-1.7%), and
      reconstructive failure (5.1%; 95% CI, 3.8%-6.7%). Five studies reported findings
      for both the ADM and non-ADM patients and were used in the meta-analysis to
      calculate pooled OR. ADM-assisted breast reconstructions had a higher likelihood
      of seroma (pooled OR, 3.9; 95% CI, 2.4-6.2), infection (pooled OR, 2.7; 95% CI,
      1.1-6.4), and reconstructive failure (pooled OR, 3.0; 95% CI, 1.3-6.8) than
      breast reconstructions without the use of ADM. The relation of ADM use to
      hematoma (pooled OR, 2.0; 95% CI, 0.8-5.2), cellulitis (pooled OR, 2.0; 95% CI,
      0.9-4.3), and skin flap necrosis (pooled OR, 1.9; 95% CI, 0.6-5.4) was
      inconclusive. CONCLUSIONS: In the studies evaluated, ADM-assisted breast
      reconstructions exhibited a higher likelihood of seroma, infection, and
      reconstructive failure than prosthetic-based breast reconstructions using
      traditional musculofascial flaps. ADM is associated with a lower rate of capsular
      contracture. A careful risk/benefit analysis should be performed when choosing to
      use ADM in implant-based breast reconstruction.

PMID- 22421477
TI  - Gynecomastia associated with herniated nipples: an optimal surgical approach.
AB  - INTRODUCTION: Gynecomastia is a common disorder observed in male plastic surgery
      patients. Treatment options may include observation, surgical excision, or
      liposuction techniques. Congenital herniated nipple is a more rare condition,
      especially in male patients. We present the case of a 12-year-old boy with
      bilateral gynecomastia and herniated nipple-areolar complexes. METHODS: A staged
      repair was undertaken in this patient with grade 2 gynecomastia. The first
      operation was ultrasonic liposuction bilaterally, yielding 200 mL of aspirate
      from the left and 400 mL on the right, to correct the gynecomastia. The second
      procedure, performed 6 months later, was a bilateral periareolar mastopexy to
      repair the herniated nipple-areolar complexes. RESULTS: The result of the first
      procedure was flattened and symmetrical breast tissue bilaterally, essentially a
      correction of the gynecomastia. The herniated nipples were still present,
      however. Bilateral periareolar mastopexies were then performed with resulting
      reduction of the herniations. There were no complications with either procedure,
      and a good cosmetic result was achieved. CONCLUSIONS: A staged surgical approach
      was successful in correcting both conditions with an excellent aesthetic result
      and the advantage of decreased risk for nipple complications.

PMID- 22421478
TI  - Surgical correction of pixie-ear defect without an exposed incision on the lobe.
AB  - Pixie ear is a condition in which the posterior edge of the helix extends
      straight down to the cheek-jaw intersection, without sweeping back up anteriorly
      to form a lobe. It occurs congenitally, but more commonly is a postoperative
      condition, following facelift surgery. Over the years, a handful of methods have
      been proposed to restore a normal earlobe contour in patients with pixie-ear
      defects, regardless of etiology. However, virtually all either result in an
      exposed scar or have limited or undocumented follow-up. The technique described
      here, resulting in a hidden scar on the mastoid-facing portion of the newly
      formed lobe and at the mastoid, behind the lobe, has been performed 26 times,
      with follow-up as long as 20 years.

PMID- 22421479
TI  - Vertical island trapezius myocutaneous flap for cervical esophagoplasty: case
      report and review of the literature.
AB  - Reconstruction of the cervical esophagus can be fraught with a variety of
      complications, such as fistula formation or stricture. Additional complicating
      factors may include local tumor recurrence, failed prior reconstruction, partial
      or total flap necrosis, and compromised tissues in an irradiated field. Once
      complications occur, the chance of a successful reconstruction in subsequent
      operations is greatly reduced. We report a case of a patient who had local tumor
      recurrence despite chemoradiotherapy necessitating cervical esophagectomy.
      Reconstruction of the esophagus was initially performed with a tubed
      anterolateral thigh flap, which was complicated by partial flap necrosis and
      salivary fistula. Since the patient was elderly and already had a pectoralis flap
      used in a previous operation, we elected to perform a vertical island trapezius
      myocutaneous flap as a salvage procedure to restore esophageal continuity.
      Postoperatively, the patient had no evidence of further fistula and was able to
      tolerate a regular diet.

PMID- 22421480
TI  - Preferences for the white female nasal supratip break.
AB  - BACKGROUND: The debate on how to create ideal facial proportions--once the remit
      of artists and sculptors--has been reignited during the past 5 decades, with the
      emergence of aesthetic facial surgery. Classic ideals exist, but few individuals
      actually satisfy these criteria. Aesthetic ideals are culturally and temporally
      variable. For centuries, the optimum nasal profile, particularly the supratip
      break (STB), has long been a matter for debate. Little is published on
      preferences for the STB. We therefore undertook a population study to determine
      the preferred angulation of the STB. METHODS: Lateral profile photographs of 10
      models were taken under standard conditions in forward gaze. The angulation of
      the STB was altered in one of the photographs of each model, so that one
      photograph had a subtle angulation of the STB and the other had a more marked
      angulation. Participants in the study were shown 2 photographs of each of the 10
      models. One hundred male and female participants were recruited to the study and
      asked to indicate their preference for the nasal tip for each of the models.
      Statistical analysis was performed using the Wilcoxon signed-rank test to
      determine significance. RESULTS: Both male and female participants in the study
      indicated an overall, and statistically significant, preference for lateral
      profile photographs showing a nasal tip with a very subtle angulation of the STB,
      compared with a larger angulation of the STB. CONCLUSIONS: This study provides
      strong evidence that a subtle STB in the white female subject is most favorable.

PMID- 22421481
TI  - Long-term reconstructive outcomes after expander-implant breast reconstruction
      with serious infectious or wound-healing complications.
AB  - INTRODUCTION: Immediate expander-implant breast reconstruction has been
      associated with postoperative complications, including infection and wound
      healing problems. In extreme cases, these issues can lead to expander-implant
      loss. Little is known about the long-term reconstructive outcomes for patients
      who develop major complications threatening their expander-implant
      reconstructions. METHODS: A review of all patients who underwent mastectomy and
      immediate expander-implant reconstruction at University of California, San
      Francisco (UCSF) from 2005 to 2007 was performed. A prospective database was
      queried for patients who developed a major postoperative complication related to
      infection or wound-healing problems requiring unplanned operative intervention.
      Only patients who had a minimum of 3 years' follow-up were included in the study.
      RESULTS: Twenty-nine patients were identified who met study criteria. Mean follow
      up time was 52.5 months (range, 41-71 months). Six of the 29 (20.7%) patients had
      received prior breast irradiation, and 9 patients (31%) underwent postoperative
      radiation therapy. Reasons for unplanned return to the operating room included
      infection (n = 11, 37.9%), expander-implant exposure (n = 5, 17.2%), nonhealing
      wounds without underlying exposure (n = 3, 1.3%), or >1 of these indications (n =
      10, 34.5%). Unplanned operative intervention (such as wound debridement or
      expander-implant exchange or removal) was required once in 10 patients (34.5%),
      twice in 10 patients (34.5%), 3 times in 4 patients (13.8%), 4 times in 1 patient
      (3.4%), and 5 or greater times in 4 patients (13.8%). At the conclusion of all
      operative interventions, 15 patients (51.7%) had successful breast reconstruction
      using an expander-implant technique. Five additional patients (17.3%) ultimately
      achieved successful salvage reconstruction with either a transverse rectus
      abdominis myocutaneous (TRAM) or deep inferior epigastric perforator (DIEP) flap.
      Nine patients (31%) did not have successful breast reconstruction. Of these 9
      patients, 5 elected to abandon reconstructive efforts after 1 unplanned return to
      the operating room for expander-implant removal, whereas the rest underwent at
      least 1 attempt at expander-implant salvage, with the overall rate of final
      successful reconstruction after attempt at salvage 83.3% (20 of 24 patients).
      CONCLUSIONS: Even when unplanned operative intervention is required to address
      postoperative wound-healing or infectious complications after expander-implant
      reconstruction, the majority of patients can achieve successful reconstructive
      outcomes at long-term follow-up, including those patients requiring multiple
      operative interventions to treat their complication.

PMID- 22421482
TI  - Outcomes of complex gunshot wounds to the hand and wrist: a 10-year level I urban
      trauma center experience.
AB  - PURPOSE: To assess the consequences of gunshot wounds (GSWs) to the hand, we
      reviewed our 10-year experience at an urban level I trauma center. METHOD: A
      retrospective review was performed on patients admitted with GSWs to the
      extremities between January 1, 1997 and January 1, 2007. Those with GSWs to the
      hand and wrist needing surgery were studied. A telephone survey supplemented the
      data. RESULTS: Of 1358 patients admitted with GSWs involving the upper
      extremities, 62 patients with complex hand and wrist injuries requiring operative
      intervention were identified. Most patients sustained low-velocity handgun
      injuries and presented within 12 hours of injury. In many individuals (97%), the
      gunshot injury to the hand or wrist was only part of a multiple gunshot assault.
      All patients underwent surgical debridement and repair followed by an early
      aggressive rehabilitation program. Mean length of hospital stay was 5.0 (+/-5.1)
      days, with 9.7% of patients requiring ICU care for 3.3 (+/-1.4) days, with an
      average cost of $47,819 (+/-$53,548) per patient. Although 65% of the individuals
      subsequently reported being "disabled from work" due to pain, the quality of
      life, and ultimate function was good in 61%, fair in 26.1%, and bad in 13%.
      CONCLUSION: GSWs to the hand and wrist are often part of multiple handgun wounds
      in one individual. Most produce comminuted fractures, seldom requiring bone
      grafts, fusion, or amputation. Vascular injuries, though rare, necessitate vein
      grafts due to loss of length. Few patients require free flaps, and few sustain
      nerve or tendon injuries. Most complain of pain or numbness. However, a good
      quality of life and a return to the activities of daily living occurred in two
      third individuals.

PMID- 22421483
TI  - Gunshot wounds to the face: level I urban trauma center:  a 10-year level I urban
      trauma center experience.
AB  - INTRODUCTION: Gunshot wounds (GSWs) to the face are an infrequent occurrence
      outside of a war zone. However, when they occur, they constitute a significant
      reconstructive challenge. We present our 10-year experience at an urban level I
      trauma center to define the patterns of injury, assess the morbidity and
      mortality, and estimate the cost to the health care system. METHODS: A
      retrospective review was performed on all patients admitted to Harbor-UCLA
      Medical Center with GSWs to the head and neck region between January 1997 and
      January 2007. Those who had sustained GSWs to the face requiring operative
      intervention were closely reviewed. RESULTS: Between 1997 and 2007, a total of
      702 patients were admitted to the Harbor UCLA Emergency Department having
      sustained GSWs to the head and neck region, of which 501 patients survived. Of
      the survivors, 28 patients (26 male, 2 female) sustained GSWs to their face
      requiring operative intervention. The mean age of these patients was 28 (+/-8.3)
      years. They generally presented within a few hours of the injury, but 1
      individual arrived over 24 hours later. Low-velocity single gunshots (from
      handguns) were predominantly involved, with facial fractures occurring in all
      cases. Fractures were of a localized shattering type without the major
      displacement of bony complexes seen in motor vehicle accidents. Most required
      wound debridement and fracture fixation. A few patients (14.2%) underwent free
      tissue transfer for reconstruction (3 fibular flaps, 1 TRAM). Tracheostomy was
      performed in 35.7% of patients. Mean length of hospital stay was 8.3 (+/-7.1)
      days, with 50% of cases requiring admission to the intensive care unit. Mean
      length of intensive care unit stay was 5.2 (+/-5.7) days. The average cost per
      patient exceeded $100,000.

PMID- 22421484
TI  - Outcomes of complex abdominal herniorrhaphy: experience with 106 cases.
AB  - PURPOSE: Reconstruction of abdominal wall defects is a challenging problem.
      Often, the surgeon is presented with a patient having multiple comorbidities, who
      has already endured numerous unsuccessful operations, leaving skin and fascia
      that are attenuated and unreliable. Our study investigated preoperative,
      intraoperative, and postoperative factors and techniques during abdominal wall
      reconstruction to determine which variables were associated with poor outcomes.
      METHODS: Data were collected on all patients who underwent ventral abdominal
      hernia repair by 3 senior-level surgeons at our institution during an 8-year
      period. In all cases, placement of either a synthetic or a biologic mesh was used
      to provide additional reinforcement of the repair. RESULTS: A total of 106
      patients were included. Seventy-nine patients (75%) had preoperative comorbid
      conditions. Sixty-seven patients developed a postoperative complication (63%).
      Skin necrosis was the most common complication (n = 21, 19.8%). Other
      complications included seroma (n = 19, 17.9%), cellulitis (n = 19, 17.9%),
      abscess (n = 14 13.2%), pulmonary embolus/deep vein thrombosis (n = 3, 2.8%),
      small bowel obstruction (n = 2, 1.9%), and fistula (n = 8, 7.5%). Factors that
      significantly contributed to postoperative complications (P < 0.05) included
      obesity, diabetes, hypertension, fistula at the time of the operation, a history
      of >2 prior hernia repairs, a history of >3 prior abdominal operations, hospital
      stay for >14 days, defect size > 300 square cm, and the use of human-derived mesh
      allograft. Factors that significantly increased the likelihood of a hernia
      recurrence (P < 0.05) included a history of >2 prior hernia repairs, the use of
      human-derived allograft, using an overlay-only mesh placement, and the presence
      of a postoperative complication, particularly infection. Hernia recurrences were
      significantly reduced (P < 0.05) by using a "sandwich" repair with both a mesh
      overlay and underlay and by using component separation. CONCLUSIONS: A history of
      multiple abdominal operations is a major predictor of complications and
      recurrences. If needed, component separation should be used to achieve primary
      tension-free closure, which helps to reduce the likelihood of hernia recurrences.
      Our data suggest that mesh reinforcement used concomitantly in a "sandwich"
      repair with component separation release may lead to reduced recurrence rates and
      may provide the optimal repair in complex hernia defects.

PMID- 22421485
TI  - The utility of multimedia in the diagnosis and management of acute and subacute
      problems in hand surgery.
AB  - A typical consultation is based on a phone conversation between the consulting
      service and the surgeon. If the description given to the surgeon misrepresents
      the severity of the condition, unnecessary transfer of the patient could follow.
      In an attempt to reduce the occurrence of unnecessary transfers, we started
      supplementing our consultation with video captured with a cell phone camera
      demonstrating specific points in clinical examination of the hand. These videos
      were sent to the surgeon to clarify the clinical picture. We found this method
      useful in some cases in ruling out the need for urgent transfer.

PMID- 22421486
TI  - "Phantom" publications among plastic surgery residency applicants.
AB  - PURPOSE: Previous studies in other medical specialties have shown a significant
      percentage of publications represented in residency applications are not actually
      published. A comprehensive evaluation of applicants to plastic surgery residency
      over an extended period has not been previously reported in the literature. The
      purpose of our study was to determine the incidence of misrepresented or
      "phantom" publications in plastic surgery residency applicants and to identify
      possible predisposing characteristics. METHODS: We used the Electronic Residency
      Application Services database to our plastic surgery residency program during a 4
      year period from 2006 to 2009. Applicant demographic information and listed
      citations were extracted. Peer-reviewed journal article citations were verified
      using robust methods including PubMed, Institute for Scientific Information (ISI)
      Web of Knowledge, and Google. Unverifiable articles were categorized as phantom
      publications and then evaluated with respect to applicant demographic information
      and characteristics. RESULTS: During the 4-year study period, there were 804
      applications (average, 201 applicants per year). There was a total of 4725
      publications listed; of which, 1975 had been categorized as peer-reviewed journal
      articles. Two hundred seventy-six (14%) of peer-reviewed publications could not
      be verified and were categorized as phantom publications. There was an overall
      significant positive trend in percentage of phantom publications during the 4
      application years (P = 0.005). A positive predictive factor for having phantom
      publications was being a foreign medical graduate (P = 0.02). A negative
      predictive factor for phantom publications was being a female applicant (P =
      0.03). There also appeared to be a positive correlation with the number of
      publications listed and likelihood of phantom publications. CONCLUSIONS: Among
      plastic surgery residency applicants, we found a significant percentage of
      unverifiable publications. There are several possible explanations for our
      findings, which include the fact that plastic surgery is a highly sought-after
      specialty and applicants may feel the need to appear competitive to residency
      programs. Publications are an important aspect of the residency selection process
      and factors into applicant ranking, but our study suggests publications listed in
      plastic surgery residency applications may not necessarily be an accurate
      representation of actual published articles. Program directors and faculty are
      advised to scrutinize listed publications carefully when evaluating applicants.

PMID- 22421487
TI  - Hospital-based plastic surgery volunteerism: a resident's international
      experience.
AB  - The purpose of this presentation is to describe an American plastic surgery
      resident's experience working for an academic year in a district-level general
      hospital in rural Kenya. The operative experience, educational value, and
      cultural adaptation over the custom-designed year are discussed. Furthermore, the
      logistics and ethics of picking a location, adjusting to the milieu, and treating
      patients are evaluated. The importance of a qualified, supportive, and perceptive
      mentor is emphasized. International volunteerism in plastic surgery beyond the
      more typical 1- or 2-week short-term trips can be extremely beneficial to a
      resident's experience, although long-term benefit to the served population should
      not be overestimated. A careful understanding of plastic surgery in relation to
      the global burden of disease highlights the fact that plastic surgery, although
      valuable, is limited in its role within international medical volunteerism. Not
      unexpectedly, obstetric, orthopedic, and general surgical skills are vital in the
      management of the most common surgical maladies.

PMID- 22421488
TI  - Is microsurgical head and neck reconstruction profitable?: analysis at an
      academic medical center.
AB  - The complexity of modern head and neck reconstruction is paralleled by
      consumption of large amounts of resources provided by both treating physicians as
      well as the institution, that is, hospital. In times of increasing economic
      constraints, analysis of the financial value of providing these services seems
      prudent. A retrospective analysis of medical and billing records of patients who
      underwent immediate microsurgical reconstruction of postablative head and neck
      defects from 2007 to 2010 at Stanford University Medical Center was performed.
      Financial data related to the treatment of 60 patients were analyzed. Total
      reimbursement for plastic surgery services was $319,609, representing a
      collection rate of 18.4%. Total hospital charges were $31,038,846.10. Actual
      reimbursement was $9,109,776.55, which represents a collection rate of 29.3%.
      Analysis of hospital revenue revealed a net profit of $1,512,136.46, which
      represents a mean net revenue of $25,202.27 per case. Microsurgical
      reconstruction secures substantial revenue for the institution. Innovative
      reimbursement models need to be implemented to attract skilled microsurgeons, who
      represent the backbone of these services.

PMID- 22421489
TI  - Plastic surgery residency graduate outcomes: a 43-year experience at a single
      institution and the first "integrated" training program in the United States.
AB  - INTRODUCTION: The Accreditation Council for Graduate Medical Education emphasizes
      outcome-based residency education. This project is an outcomes study on graduates
      of the Stanford University Integrated Plastic Surgery Residency. METHODS: A
      survey assessing various outcomes, including practice profile, financial,
      personal, and educational issues, was electronically distributed to all 130
      graduates between 1966 and 2009. RESULTS: There was a 65% response rate. Nearly
      all respondents are currently in practice. Popular fellowships included hand and
      microsurgery. Most respondents participated in research and held leadership
      roles. Adequate residency education was noted in areas of patient care, board
      preparation, and ethical and legal issues. Inadequate residency education was
      noted in areas of managing a practice, coding, and cost-effective medicine.
      CONCLUSIONS: This is the first long-term outcomes study of plastic surgery
      graduates. Most are in active, successful practice. We have incorporated
      educational content related to running a small business, contract negotiating,
      and marketing to better prepare our residents for future practice.

PMID- 22421490
TI  - Microsurgery education in residency training: validating an online curriculum.
AB  - INTRODUCTION: Plastic surgery training has traditionally been modeled as an
      "apprenticeship," where faculty teach surgical skills to residents on live
      patients. Although this is a well-established process, the demand by the public
      and healthcare agencies for improved patient care, outcomes, and patient safety
      has led to the development of adjunct methods of teaching. The goal of this
      project is to assess the effectiveness of a web-based microsurgical curriculum.
      METHODS: We developed an interactive Web site to teach essential microsurgical
      competencies. Residents were randomly divided into 2 cohorts: one experimental
      group completed this online resource and the other control group did not. Pre-
      and postassessments were administered, consisting of a written test and a
      recorded microsurgery skills session. RESULTS: A total of 17 plastic surgery
      residents of various training levels participated in the study. Residents who
      completed the web-based curriculum showed dramatic improvement in their knowledge
      and skills, with a 17-percentage point increase in their test scores (P = 0.01)
      compared with controls (P = 0.80). The experimental group was more likely to
      perform microanastomoses faster with an average of 4.5-minute improvement
      compared with 1.25-minute change among the control group. Residents performed
      self-assessments, and those who rated themselves as "very confident" had higher
      overall test scores (85% test score vs. 59%, P = 0.004), as well as shorter times
      to complete the microsurgical task (7.5 minutes vs. 13.6 minutes, P = 0.007).
      Overall, 62% of residents rated the online webpage as extremely valuable. The
      majority of residents reported the webpage improved their knowledge and markedly
      improved their microsurgical technique, which was confirmed by faculty experts.
      CONCLUSIONS: Our interactive Web-based curriculum is a novel resource, teaching
      microsurgery in an organized, competency-based manner, which we believe is the
      first Web site of this nature. An individualized, self-paced Web site is ideal
      for plastic surgery trainees of all levels. Overall, the widespread
      implementation of our proposed curriculum--online self-directed training combined
      with regular practice sessions--will establish a strong foundation of
      microsurgery knowledge and skills acquisition for all plastic surgery residents.

PMID- 22421491
TI  - Telemedicine as a means of effective speech evaluation for patients with cleft
      palate.
AB  - Providing long-term multidisciplinary care for cleft lip/palate is a challenge
      for international humanitarian organizations that perform surgery across borders.
      The use of telemedicine as a means of evaluating speech in patients with cleft
      lip/palate has not been studied previously. We looked at determining whether a
      speech evaluation performed by a speech-language pathologist (SLP) using
      telemedicine would be equivalent to a speech evaluation performed in-person, in
      an international setting between Tijuana, Mexico and San Diego, CA. Spanish
      speaking SLPs developed an informal protocol to evaluate several speech
      characteristics. Patients were simultaneously evaluated by 2 SLPs, one in-person
      in Tijuana and the other over telemedicine videoconference from San Diego, CA. In
      addition, we obtained data regarding the parents experience with telemedicine
      through a satisfaction survey. Results showed no statistically significant
      differences between the 2 methods of speech evaluation, particularly in oral
      muscle tone, resonance, lingual lateralization, oral pressure, and dentition. The
      satisfaction survey showed family satisfaction with the speech evaluation
      performed using telemedicine. Thus, telemedicine represents an effective medium
      for conducting speech assessment in patients with cleft lip/palate, allowing for
      increased access to care for underserved populations.

PMID- 22421492
TI  - On farm evaluation of the coproantigen ELISA and coproantigen reduction test in
      Scottish sheep naturally infected with Fasciola hepatica.
AB  - The liver fluke, Fasciola hepatica, is a cause of significant economic losses in
      sheep farming. Lack of convenient and sensitive diagnostic tests in the live
      animal hampers the ability to monitor infection status and treatment efficacy.
      Use of a coproantigen ELISA and coproantigen reduction test, based on this ELISA,
      may address these issues but has, to date, only been evaluated in experimental
      challenge studies. We evaluated the coproantigen ELISA under working farm
      conditions in Scotland to assess its usefulness as a diagnostic test for liver
      fluke infection and as a diagnostic test to help determine the efficacy of
      flukicide treatment in sheep. First, liver fluke infection status was monitored
      longitudinally in a group of lambs, using monthly blood samples for biochemical
      assays and serum antibody ELISA and using monthly faecal samples for faecal egg
      count (FEC) and coproantigen ELISA. The average serum antibody ELISA titre became
      positive in September, two months ahead of faecal indicators of fluke infection.
      In contrast to results from experimental challenge studies, FEC and coproantigen
      ELISA became positive at the same time point. Secondly, treatment efficacy was
      measured in 100 ewes, from two farms, after treatment with triclabendazole (TCBZ)
      or closantel. Group level estimates of treatment efficacy were similar between
      faecal egg count reduction testing and coproantigen reduction testing at 7, 14
      and 21 days post treatment. For individual animals, some inconsistencies between
      tests were observed. TCBZ treatment failure was noted on both farms, despite
      accurate weighing of animals and dosing of treatment products. We conclude that
      (1) coproantigen ELISA is a more convenient test than faecal egg counts and holds
      promise as a diagnostic tool for natural fluke infections in sheep but further
      evaluation of interpretation criteria may be needed; (2) the coproantigen ELISA
      has performed differently in the field compared with experimental challenge
      studies in sheep and (3) TCBZ-resistant fluke were present on both farms.

PMID- 22421493
TI  - Hepatobiliary cystadenoma of the liver prolapsing into the extrahepatic bile duct
      (with video).

PMID- 22421494
TI  - Diagnostic yield of EUS-guided FNA and cytology in suspected tubercular intra
      abdominal lymphadenopathy.
AB  - BACKGROUND: Intra-abdominal lymphadenopathy is a common diagnostic challenge
      faced by clinicians. In the absence of palpable peripheral nodes, tissue is
      usually obtained from the abdominal nodes by image-guided biopsy or surgery. We
      speculate that EUS-guided FNA (EUS-FNA) avoids the morbidity of a laparotomy and
      might be equally effective. OBJECTIVE: To evaluate the role of EUS-FNA in
      abdominal lymphadenopathy. DESIGN: Prospective study conducted over 42 months.
      SETTING: Tertiary care center in New Delhi, India. PATIENTS: Patients with
      abdominal lymphadenopathy in whom image-guided node biopsy failed were considered
      for EUS-FNA. INTERVENTION: A total of 3 passes were performed at each site.
      Slides were prepared per protocol and sent for cytopathologic evaluation.
      RESULTS: A total of 142 patients were enrolled, but only 130 (91.5%) underwent
      FNA. The mean lymph node size was 22 +/- 3.2 mm; 71.8% of the nodes were
      hypoechoic (n = 102), and 28.1% were heterogeneous with an anechoic center (n =
      40). In 120 patients (84.5%), the lymph nodes were intra-abdominal only, and in
      22 patients (15.5%), they were both intra-abdominal and mediastinal in location.
      MAIN OUTCOME MEASUREMENT: EUS-FNA was successful in establishing a diagnosis in
      90.8% of these patients; 76.1% were found to have tuberculosis, 7.04%
      sarcoidosis, 6.33% Hodgkin's lymphoma, and 0.74% non-Hodgkin's lymphoma.
      LIMITATIONS: In 8.4% patients, nodes were inaccessible because of their
      retropancreatic location. CONCLUSIONS: EUS-FNA is a safe, accurate, and minimally
      invasive modality for diagnosing the cause of abdominal lymphadenopathy. In
      highly endemic areas, tuberculosis is the most common cause.

PMID- 22421495
TI  - Endoscopic treatment of congenital duodenal membrane.

PMID- 22421496
TI  - Randomized crossover study comparing efficacy of transnasal endoscopy with that
      of standard endoscopy to detect Barrett's esophagus.
AB  - BACKGROUND: Unsedated transnasal endoscopy (TNE) may be safer and less expensive
      than standard endoscopy (SE) for detecting Barrett's esophagus (BE). Emerging
      technologies require robust evaluation before routine use. OBJECTIVE: To evaluate
      the sensitivity, specificity, and acceptability of TNE in diagnosing BE compared
      with those of SE. DESIGN: Prospective, randomized, crossover study. SETTING:
      Single, tertiary-care referral center. PATIENTS: This study enrolled consecutive
      patients with BE or those referred for diagnostic assessment. INTERVENTION: All
      patients underwent TNE followed by SE or the reverse. Spielberger State-Trait
      Anxiety Inventory short-form questionnaires, a visual analogue scale, and a
      single question addressing preference for endoscopy type were administered. MAIN
      OUTCOME MEASUREMENTS: Diagnostic accuracy and tolerability of TNE were compared
      with those of SE. RESULTS: Of 95 patients randomized, 82 completed the study. We
      correctly diagnosed 48 of 49 BE cases by TNE for endoscopic findings of columnar
      lined esophagus compared with the criterion standard, SE, giving a sensitivity
      and specificity of 0.98 and 1.00, respectively. The BE median length was 3 cm
      (interquartile range [IQR] 1-5 cm) with SE and 3 cm (IQR 2-4 cm) with TNE, giving
      high correlations between the two modalities (R(2) = 0.97; P < .001). The
      sensitivity and specificity for detecting intestinal metaplasia by TNE compared
      with those by SE was 0.91 and 1.00, respectively. The mean (+/- standard
      deviation) post-endoscopy Spielberger State-Trait Anxiety Inventory short-form
      score for TNE (30.0 +/- 1.10 standard error of the mean [SEM]) was lower than
      that for SE (30.7 +/- 1.29 SEM), (P = .054). The visual analogue scale scores
      were no different (P = .07). The majority of patients (59%) expressed a
      preference for TNE. LIMITATIONS: This is a small study, with limited
      generalizability, a high prevalence of patients with BE, differential drop-out
      between the two procedures, and use of sedation. CONCLUSION: TNE is an accurate
      and well-tolerated method for diagnosing BE compared with SE. TNE warrants
      further evaluation as a screening tool for BE.

PMID- 22421497
TI  - An unusual cause of lower GI bleeding in a young woman: metastatic gestational
      choriocarcinoma.

PMID- 22421498
TI  - Knowledge of quality performance measures associated with endoscopy among
      gastroenterology trainees and the impact of a web-based intervention.
AB  - BACKGROUND: Knowledge of quality measures in endoscopy among trainees is unknown.
      OBJECTIVE: To assess knowledge of endoscopy-related quality indicators among U.S.
      trainees and determine whether it improves with a Web-based intervention. DESIGN:
      Randomized, controlled study. SETTING: Multicenter. PARTICIPANTS: This study
      involved trainees identified from the American Society for Gastrointestinal
      Endoscopy membership database. INTERVENTION: Participants were invited to
      complete an 18-question online test. Respondents were randomized to receive a Web
      based tutorial (intervention) or not. The test was readministered 6 weeks after
      randomization to determine the intervention's impact. MAIN OUTCOME MEASUREMENTS:
      Baseline knowledge of endoscopy-related quality indicators and impact of the
      tutorial. RESULTS: A total of 347 of 1220 trainees (28%) completed the test; the
      mean percentage of correct responses was 55%. For screening colonoscopy, 44% knew
      the adenoma detection rate benchmark, 42% identified the cecal intubation rate
      goal, and 74% knew the recommended minimum withdrawal time. A total of 208 of 347
      trainees (59%) completed the second test; baseline scores were similar for the
      tutorial (n = 106) and no tutorial (n = 102) groups (56.4% vs 56.9%,
      respectively). Scores improved after intervention for the tutorial group (65%, P
      = .003) but remained unchanged in the no tutorial group. On multivariate
      analysis, each additional year in training (odds ratio [OR] 2.3; 95% confidence
      interval [CI], 1.5-3.4), training at an academic institution (OR 2.6; 95% CI, 1.1
      6.3), and receiving the tutorial (OR 3.2; 95% CI, 1.7-5.9) were associated with
      scores in the upper tertile. LIMITATIONS: Low response rate. CONCLUSION:
      Knowledge of endoscopy-related quality performance measures is low among trainees
      but can improve with a Web-based tutorial. Gastroenterology training programs may
      need to incorporate a formal didactic curriculum to supplement practice-based
      learning of quality standards in endoscopy.

PMID- 22421499
TI  - New information concerning the history of the Olavide Museum and its wax models.

PMID- 22421500
TI  - Perianal ulcers on a segmental hemangioma with minimal or arrested growth.
AB  - Hemangiomas with minimal or arrested growth are a type of infantile hemangioma in
      which the proliferative component characteristic of such lesions is not observed
      or accounts for less than 25% of the surface area of the hemangioma. For this
      reason, these lesions are frequently confused with capillary vascular
      malformations or may even go undetected. Awareness of these lesions is, however,
      important because they can become ulcerated, as occurs with typical infantile
      hemangiomas. A proper diagnosis is therefore important to enable administration
      of appropriate treatment. We present the case of a 3-month-old girl with slowly
      progressing perianal ulcers first detected when she was 20 days old. She had
      received many different therapies without any response. A pathology study of the
      ulcer showed a GLUT-1-positive infantile hemangioma. Response to treatment with
      propranolol 2mg/kg/d and local wound care was excellent.

PMID- 22421502
TI  - [Multiple cutaneous metastases from hepatocellular carcinoma as the first sign of
      tumor recurrence in a transplant patient].

PMID- 22421501
TI  - [Atypical lentiginous nevus: a clinical and histopathologic study of 14 cases].
AB  - BACKGROUND: Atypical lentiginous nevus (of the elderly) is a peculiar form of
      dysplastic nevus. Clinically, this condition can resemble malignant melanoma and
      histologically, it has a lentiginous pattern with variable degrees of atypia and
      an absence of dermal nests. These features may lead to an erroneous diagnosis of
      lentigo maligna melanoma or lentiginous melanoma. MATERIAL AND METHODS: We
      reviewed 14 cases of atypical lentiginous nevus diagnosed at the dermatology
      department of Hospital General de Valencia in Valencia, Spain between December
      2007 and March 2009. We studied the clinical and histopathologic features of the
      lesions after hematoxylin-eosin, Melan-A, and Ki-67 staining and compared our
      results to data reported in the literature. RESULTS: Four (28%) of the 14
      patients (7 men, 7 women) were under 50 years of age. Clinically, most of the
      lesions (8/14) resembled atypical nevi and they were all located on the back.
      Histologically, they all had irregular lentiginous epidermal hyperplasia, with a
      proliferation of individual melanocytes only in the basal layer of the epidermis
      and an absence of dermal nests. Focal upward migration of melanocytes into the
      epidermis was present in just 4 cases. All the lesions had cellular atypia, which
      was moderate in 85% of cases. The Ki-67 proliferation index was low (<5%) in all
      the lesions analyzed. CONCLUSIONS: Atypical lentiginous nevi, which can be
      classified as atypical pigmented lesions with a lentiginous pattern, may
      clinically and histologically resemble melanoma. Our findings support earlier
      reports that both clinical and histologic findings may suggest a diagnosis of
      dysplastic nevus. All of the patients in our series are healthy and free of
      recurrence after 18 months or longer.

PMID- 22421503
TI  - A Bayesian zero-truncated approach for analysing capture-recapture count data
      from classical scrapie surveillance in France.
AB  - Capture-recapture (CR) methods are used to study populations that are monitored
      with imperfect observation processes. They have recently been applied to the
      monitoring of animal diseases to evaluate the number of infected units that
      remain undetected by the surveillance system. This paper proposes three bayesian
      models to estimate the total number of scrapie-infected holdings in France from
      CR count data obtained from the French classical scrapie surveillance programme.
      We fitted two zero-truncated Poisson (ZTP) models (with and without holding size
      as a covariate) and a zero-truncated negative binomial (ZTNB) model to the 2006
      national surveillance count dataset. We detected a large amount of heterogeneity
      in the count data, making the use of the simple ZTP model inappropriate. However,
      including holding size as a covariate did not bring any significant improvement
      over the simple ZTP model. The ZTNB model proved to be the best model, giving an
      estimation of 535 (CI(95%) 401-796) infected and detectable sheep holdings in
      2006, although only 141 were effectively detected, resulting in a holding-level
      prevalence of 4.40/00 (CI(95%) 3.2-6.3) and a sensitivity of holding-level
      surveillance of 26% (CI(95%) 18-35). The main limitation of the present study was
      the small amount of data collected during the surveillance programme. It was
      therefore not possible to build complex models that would allow depicting more
      accurately the epidemiological and detection processes that generate the
      surveillance data. We discuss the perspectives of capture-recapture count models
      in the context of animal disease surveillance.

PMID- 22421504
TI  - Correlation of noninvasive markers of cardiac allograft rejection with
      endomyocardial biopsy: a case report.
AB  - Although endomyocardial biopsy remains the gold standard to diagnose cardiac
      allograft rejection, the search continues for clinical parameters that may aid in
      the early diagnosis of rejection. We report the case of a 29-year-old man who
      underwent orthotopic heart transplantation and subsequently had multifocal
      moderate allograft rejection. During the patient's hospital course, he exhibited
      a number of clinical parameters that served as important clues for the worsening
      rejection. After aggressive immunosuppression, the improvement of these markers
      hinted toward his eventual recovery.

PMID- 22421505
TI  - Complete heart block in takotsubo cardiomyopathy.
AB  - Tako-tsubo cardiomyopathy is a relatively recently recognized clinical entity,
      which presents similar to an acute myocardial infarction but there is no evidence
      of obstructive coronary artery disease on cardiac catheterization. It mostly
      affects postmenopausal women and an episode of acute illness or stress can often
      be identified preceding the presentation. Tako-tsubo cardiomyopathy (TCM) usually
      has a favorable outcome and an excellent prognosis but, in rare instances, it can
      be associated with life threatening complications. We report a unique case of TCM
      where the patient presented with a transient complete heart block.

PMID- 22421506
TI  - Association of body mass index with exercise cardiopulmonary responses in lung
      function-matched patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND AND OBJECTIVES: Lung function is traditionally used to define the
      severity of chronic obstructive pulmonary disease (COPD). However, this does not
      exclude other factors. This study investigated the influence of body mass index
      (BMI) on exercise responses and quality of life in patients with COPD matched for
      values of forced expiratory volume in 1 second (FEV(1)). METHODS: Underweight,
      normal-weight, and overweight patients with COPD, matched for FEV(1), were
      studied. All patients were evaluated by spirometry, a cardiopulmonary exercise
      test, respiratory muscle strength, and, St. George's Respiratory Questionnaire
      (SGRQ). RESULTS: The baseline characteristics and mean FEV(1) of the 3 groups
      were similar (P > .05). Respiratory muscle strengths and SGRQ scores were lowest
      in underweight patients (P < .05). In terms of exercise response, the lowest
      oxygen uptake at anaerobic threshold and peak exercise, the highest ventilatory
      equivalent, and the lowest oxygen pulse were evident in underweight patients (P <
      .05). CONCLUSIONS: Underweight patients with COPD had lower respiratory muscle
      strength, impaired exercise capacity, earlier anaerobic metabolism, ineffective
      ventilation, and poorer quality of life.

PMID- 22421508
TI  - B-type natriuretic peptide predicts new-onset atrial fibrillation in patients
      with ST-segment elevation myocardial infarction treated by primary percutaneous
      coronary intervention.
AB  - The predictive value of B-type natriuretic peptide (BNP) with respect to the
      occurrence of new-onset atrial fibrillation (AF) in patients with ST-segment
      elevation myocardial infarction (STEMI) treated by primary percutaneous coronary
      intervention (PCI) is unknown. The aim of this study was to evaluate whether BNP
      has a predictive value for the occurrence of new-onset AF in patients with STEMI
      treated by primary PCI. In 180 patients with STEMI treated by primary PCI, BNP
      concentrations were measured 24h after chest pain onset. The Receiver Operating
      Characteristic analysis was performed to identify the most useful BNP cut-off
      level for the prediction of AF. The patients were divided into the two groups
      according to calculated cut-off level: high BNP group (BNP>=720 pg/mL, n=33) and
      low BNP group (BNP<720 pg/mL, n=147). The incidence of AF was 5.0%, and occurred
      more frequently in high BNP group (7/33, 21.2%) than in low BNP group (2/147,
      1.4%), (p<0.001). Patients with high BNP were older (p=0.017), had more often
      anterior wall infarction (p=0.015), higher Killip class on admission (p=0.038),
      higher peak troponin I (p=0.002), lower left ventricular ejection fraction
      (p=0.029) than patients with low BNP. After multivariate adjustment, BNP was an
      independent predictor of AF (OR 3.70, 95% CI 1.40-9.77, p=0.008). BNP
      independently predicts the occurrence of new-onset AF in STEMI patients treated
      by primary PCI.

PMID- 22421507
TI  - Erythropoietin neuroprotection with traumatic brain injury.
AB  - Numerous experimental studies in recent years have suggested that erythropoietin
      (EPO) is an endogenous mediator of neuroprotection in various central nervous
      system disorders, including TBI. Many characteristics of EPO neuroprotection that
      have been defined in TBI experimental models suggest that it is an attractive
      candidate for a new treatment of TBI. EPO targets multiple mechanisms known to
      cause secondary injury after TBI, including anti-excitotoxic, antioxidant, anti
      edematous, and anti-inflammatory mechanisms. EPO crosses the blood-brain barrier.
      EPO has a known dose response and time window for neuroprotection and
      neurorestoration that would be practical in the clinical setting. However, EPO
      also stimulates erythropoiesis, which can result in thromboembolic complications.
      Derivatives of EPO which do not bind to the classical EPO receptor (carbamylated
      EPO) or that have such a brief half-life in the circulation that they do not
      stimulate erythropoiesis (asialo EPO and neuro EPO) have the neuroprotective
      activities of EPO without these potential thromboembolic adverse effects
      associated with EPO administration. Likewise, a peptide based on the structure of
      the Helix B segment of the EPO molecule that does not bind to the EPO receptor
      (pyroglutamate Helix B surface peptide) has promise as another alternative to EPO
      that may provide neuroprotection without stimulating erythropoiesis.

PMID- 22421509
TI  - Biosynthesis of proTRH-derived peptides in prohormone convertase 1 and 2 knockout
      mice.
AB  - Prohormone convertases (PCs) 1 and 2 are the primary endoproteases involved in
      the post-translational processing of proThyrotropin Releasing Hormone (proTRH) to
      give rise to TRH and other proposed biologically active non-TRH peptides.
      Previous evidence suggests that PC1 is responsible for most proTRH cleavage
      events. Here, we used the PC1 and PC2 knockout (KO) mouse models to examine the
      effects of PC1 or PC2 loss on proTRH processing. The PC1KO mouse presented a
      decrease in five proTRH-derived peptides, whereas the PC2KO mouse showed only
      lesser reduction in three TRH (Gln-His-Pro), TRH-Gly (Gln-His-Pro-Gly), and the
      short forms preproTRH(178-184) (pFQ(7)) and preproTRH(186-199) (pSE(14)) of
      pFE(22) (preproTRH(178-199)). Also, PC1KO and not PC2KO showed a decrease in
      pEH(24) indicating that PC1 is more important in generating this peptide in the
      mouse, which differs from previous studies using rat proTRH. Furthermore,
      downstream effects on thyroid hormone levels were evident in PC1KO mice, but not
      PC2KO mice suggesting that PC1 plays the more critical role in producing
      bioactive hypophysiotropic TRH. Yet loss of PC1 did not abolish TRH entirely
      indicating a complementary action for both enzymes in the normal processing of
      proTRH. We also show that PC2 alone is responsible for catalyzing the conversion
      of pFE(22) to pFQ(7) and pSE(14), all peptides implicated in regulation of
      suckling-induced prolactin release. Collectively, results characterize the
      specific roles of PC1 and PC2 in proTRH processing in vivo.

PMID- 22421510
TI  - Orexin receptor type-1 antagonist SB-334867 inhibits the development of morphine
      analgesic tolerance in rats.
AB  - Herein the effect of orexin receptor type-1 antagonist SB-334867 on the
      development of tolerance to analgesic effects of morphine was studied in rats. To
      incite tolerance, morphine sulfate was injected intraperitoneally (i.p., 10mg/kg)
      once a day for 7 days. The tail flick test was used to evaluate antinociceptive
      effects of the morphine. A selective OxR1 receptor antagonist, SB-334867, was
      microinjected (i.c.v.) into the right cerebral ventricle (10 MUg/10 MUl)
      immediately before each morphine injection. Repeated morphine application
      resulted in tolerance to morphine analgesic effects as a decreasing trend during
      7 days. Also, repeated administration of SB-334867 (i.c.v.) alone was without
      significant effect on the nociception as compared to control. Microinjection of
      SB-334867 prior to each morphine injection inhibited the development of
      tolerance, so that the analgesic effects of morphine were significantly higher in
      SB-334867 plus morphine treated rats than that of vehicle plus morphine treated
      ones on days 4-7. It is concluded that orexin receptor type-1 might be involved
      in the development of tolerance to morphine analgesic effects.

PMID- 22421511
TI  - Apicobasal polarity in the kidney.
AB  - The apicobasal polarization of epithelia is critical for many aspects of kidney
      function. Over the last decade there have been major advances in our
      understanding of the mechanisms that underlie this polarity. Critical to this
      understanding has been the identification of protein complexes on the apical and
      basolateral sides of epithelial cells that act in a mutually antagonistic manner
      to define these domains. Concomitant with the creation of apical and basolateral
      domains is the formation of highly specialized cell-cell junctions including
      adherens junctions and tight junctions. Recent research points to variability in
      the polarity and junctional complexes amongst different species and between
      different cell types of the kidney. Defects in apicobasal polarity are prominent
      in several disorders including acute renal failure and polycystic kidney disease.

PMID- 22421512
TI  - Podocytes: gaining a foothold.
AB  - In an attempt to understand the basis of glomerular disease, significant progress
      has been made in understanding the mechanisms that determine podocyte development
      and the maintenance of podocyte health. This review examines recent advances in
      this area focusing on the podocyte intercellular junction, actin cytoskeletal
      dynamics, and determinants of podocyte cell polarity, autophagy and mTOR biology.

PMID- 22421515
TI  - Testosterone deficiency in older men: a problem worth treating.
AB  - Testosterone levels decrease with normal aging, and researchers estimate that
      more than 4.5 million American men may have symptoms related to low testosterone.
      Termed late-onset hypogonadism (LOH), low testosterone levels in older men may be
      associated not only with symptoms such as depressed mood and fatigue, but also
      comorbidities such as diabetes and heart failure. Understanding the symptoms,
      diagnosis, and treatment of LOH is important for all practitioners who care for
      older men.

PMID- 22421513
TI  - Role of FGF23 in vitamin D and phosphate metabolism: implications in chronic
      kidney disease.
AB  - FGF23 is a bone-derived hormone that regulates systemic phosphate homeostasis,
      vitamin D metabolism and alpha-Klotho expression through a novel bone-kidney
      axis. FGF23 inhibits renal tubular reabsorption of phosphate through mechanisms
      independent of PTH as well as reduces circulating 1, 25(OH)(2)D through its dual
      effects to suppress Cyp27b1 production and to stimulate Cyp24 catabolism of
      1,25(OH)(2)D. 1,25(OH)(2)D and other factors regulating bone
      remodeling/mineralization are the major physiological regulators of FGF23
      expression. FGF23 also suppresses the gene transcription of alpha-klotho by the
      kidney, which exists as a membrane and soluble protein. Membrane Klotho acts as a
      coreceptor for and dictates organ specificity of FGF23, whereas soluble Klotho
      act as an endocrine factor that regulates activity of cell surface glycoproteins
      and receptors in multiple tissues. Elevated FGF23 levels are responsible for
      several hereditary and acquired hypophosphatemic rickets disorders. FGF23 and
      Klotho deficiency have similar phenotypes characterized by hyperphosphatemia,
      elevated 1,25(OH)(2)D and tumoral calcinosis. FGF23 levels progressively increase
      during chronic kidney disease (CKD). FGF23 has been proposed to be the initial
      adaptive response leading to reductions in 1,25(OH)(2)D and secondary
      hyperparathyroidism (HPT) in CKD. The overall biological effect of this initial
      step may be to orchestrate a coordinated adaptation to protect the organism from
      the adverse effects of excess phosphate retention. The second step involves the
      effects of PTH on bone remodeling that further stimulates FGF23 production
      through both direct and indirect mechanisms related to alterations in
      extracellular matrix factors. PTH further amplifies FGF23 expression in later
      stages of CKD to compensate for the increased phosphate efflux from bone caused
      by excessive bone turnover. While many aspects of the regulation and functions of
      FGF23 remain to be established, the idea that FGF23 hormone is the initial
      adaptive hormonal response in CKD that suppresses 1,25(OH)(2)D, reduces
      gastrointestinal calcium and phosphate absorption and leads to a secondary HPT
      represents a paradigm shift in the conceptualization of the pathogenesis of
      secondary hyperparathyroidism. In addition, the prevalent thought that CKD is a
      functional "vitamin D deficient state" requiring therapy with 1,25(OH)(2)D
      analogs is challenged by effects of FGF23 to potentially lower both 25(OH)D and
      1,25(OH)D by induction of Cyp24-mediated degradation. Finally, increments in
      FGF23 are associated with increased cardiovascular mortality in CKD. Whether
      these effects represent direct effects of FGF23 or represent a marker of other
      abnormalities in CKD remains to be determined.

PMID- 22421514
TI  - MicroRNAs and the glomerulus.
AB  - MicroRNAs (miRNAs) are short non-coding RNAs regulating gene expression at the
      post-transcriptional level by blocking translation or promoting cleavage of their
      target mRNAs. Increasing evidence shows that miRNAs play central roles in gene
      transcription, signal transduction and pathogenesis of human diseases. Diabetic
      nephropathy (DN) is a severe microvascular complication that can lead to end
      stage renal disease. Increased expansion (hypertrophy) and accumulation of
      extracellular matrix (ECM) proteins such as collagen (fibrosis) in the glomerular
      mesangium along with glomerular podocyte dysfunction are major features of DN.
      Profiling of miRNAs and study? of their functions in renal glomeruli can provide
      critical new information to advance our knowledge of DN as well as other kidney
      diseases and thereby uncover much needed new therapeutic targets. In this review,
      we summarize the biogenesis of miRNAs and their functions in the glomerulus, with
      particular emphasis on glomerular mesangial cells and podocytes related to the
      pathogenesis of DN.

PMID- 22421516
TI  - Carving out the pharmacist's role in the elusive ACO.
AB  - Accountable care organizations (ACOs) were established as part of the Affordable
      Care Act, the health care reform act signed by President Obama in 2010. An ACO,
      comprising a network of physicians and facilities that managed the health care
      needs of Medicare beneficiaries, is an innovative model for delivering health
      care services. While pharmacist involvement in ACOs is not federally mandated,
      their skills and experience suggest that they can play a viable role in these
      organizations. The medication-related activities that the ACO will need to
      provide are consistent with those currently being performed by consultant
      pharmacists in long-term care, so there could well be opportunities for these
      practitioners as ACOs are established and evolve.

PMID- 22421517
TI  - Reducing unnecessary hospital readmissions: the pharmacist's role in care
      transitions.
AB  - OBJECTIVE: Nearly one in five Medicare patients is readmitted to a hospital
      within 30 days of discharge. Most of these admissions are preventable, coming at
      a cost both to the patient's health and function and resulting in unnecessary
      health expenditures. With nearly two-thirds of postdischarge adverse events
      attributed to medications, pharmacists are uniquely suited to implement a
      homebased care transitions program with the goal of reducing unnecessary 30-day
      readmissions. SETTING: Our model of care, which has been implemented by Medicare
      Advantage plans in Massachusetts and California, focuses on the transition from
      the acute and subacute setting to home. PRACTICE DESCRIPTION: Within the first
      few days following discharge from acute or subacute facilities, the pharmacist
      visits patients in their homes. PRACTICE INNOVATION: In collaboration with other
      health care providers, the pharmacist reconciles and optimizes medications from
      the multiple settings of care. In addition, he or she provides care management
      and ongoing support for 30 days postdischarge. MAIN OUTCOME MEASUREMENTS: The
      pharmacists' involvement in an interdisciplinary home-based transitions of care
      program provides patients with medication and care-management interventions that
      reduce 30-day readmission rates. RESULTS: Over the past two years, Dovetail
      Health has demonstrated up to 30% reductions in network readmission rates for our
      health plan and provider group partners. CONCLUSIONS: The novel role of the
      pharmacist in managing patient transitions of care from one site to another not
      only reduces unnecessary health care utilization and cost, but more importantly
      benefits the patient, who remains healthy at home following a hospitalization.

PMID- 22421518
TI  - Gastrointestinal bleeding and possible hypothyroidism.
AB  - An 88-year-old female, living independently in the community, developed duodenal
      and gastric ulcers from using overthe-counter naproxen sodium for pain related to
      a shoulder fracture and arthritis of the knees. She was hospitalized and received
      packed red blood cells and intravenous proton pump inhibitor therapy. During her
      hospitalization, she developed atrial fibrillation (AF). Warfarin was not
      prescribed for stroke prevention because of the gastrointestinal (GI) bleeding.
      The patient was initially placed on atenolol, and then amiodarone was added.
      After a two-week hospital stay she was discharged to a nursing facility to gain
      strength, further correct her anemia, and receive physical therapy for the
      shoulder and ambulation problems from arthritis of the knees. The amiodarone was
      continued in the nursing facility. After 15 days of amiodarone therapy (hospital
      and nursing facility), a laboratory report indicated an elevated thyroid
      stimulating hormone level. Levothyroxine was prescribed. The patient was
      eventually discharged to an assisted living facility once her strength returned
      and her ambulation improved. GI bleeding with anemia and weakness from
      nonsteroidal anti-inflammatory drug use and changes in thyroid function with
      amiodarone therapy for AF will be discussed.

PMID- 22421519
TI  - Clinical Considerations for Roflumilast: A New Treatment for COPD.
AB  - Chronic obstructive pulmonary disease (COPD) causes significant morbidity and
      mortality and represents the fourth leading cause of death in the world.
      Roflumilast is the first oral phosphodiesterase inhibitor indicated to reduce the
      risk of COPD exacerbations in patients with severe COPD associated with chronic
      bronchitis and history of exacerbations. Roflumilast and its active metabolite
      have been associated with increased cyclic adenosine monophosphate (cyclic AMP)
      in the lungs and positive responses with inflammatory markers. Significant
      improvements in forced expiratory volume (1 sec) have been observed in clinical
      trials comparing roflumilast with placebo. Combination therapy of roflumilast
      (500 MUg) with long-acting beta agonists resulted in reduced COPD exacerbations
      in patients with severe COPD. Adverse effects include weight loss, diarrhea,
      nausea, and psychiatric disturbances. Roflumilast may be associated with
      significant drug-drug interactions with CYP3A4 inducers (strong) and
      immunosuppressants. Roflumilast is a promising new agent in the treatment of
      COPD; however, additional studies comparing roflumilast with inhaled
      corticosteroids plus long-acting bronchodilators are needed.

PMID- 22421520
TI  - Semantic similarity-based alignment between clinical archetypes and SNOMED CT: an
      application to observations.
AB  - PURPOSE: One of the main challenges of eHealth is semantic interoperability of
      health systems. But, this will only be possible if the capture, representation
      and access of patient data is standardized. Clinical data models, such as OpenEHR
      Archetypes, define data structures that are agreed by experts to ensure the
      accuracy of health information. In addition, they provide an option to normalize
      clinical data by means of binding terms used in the model definition to standard
      medical vocabularies. Nevertheless, the effort needed to establish the
      association between archetype terms and standard terminology concepts is
      considerable. Therefore, the purpose of this study is to provide an automated
      approach to bind OpenEHR archetypes terms to the external terminology SNOMED CT,
      with the capability to do it at a semantic level. METHODS: This research uses
      lexical techniques and external terminological tools in combination with context
      based techniques, which use information about structural and semantic proximity
      to identify similarities between terms and so, to find alignments between them.
      The proposed approach exploits both the structural context of archetypes and the
      terminology context, in which concepts are logically defined through the
      relationships (hierarchical and definitional) to other concepts. RESULTS: A set
      of 25 OBSERVATION archetypes with 477 bound terms was used to test the method. Of
      these, 342 terms (74.6%) were linked with 96.1% precision, 71.7% recall and 1.23
      SNOMED CT concepts on average for each mapping. It has been detected that about
      one third of the archetype clinical information is grouped logically. Context
      based techniques take advantage of this to increase the recall and to validate a
      30.4% of the bindings produced by lexical techniques. CONCLUSIONS: This research
      shows that it is possible to automatically map archetype terms to a standard
      terminology with a high precision and recall, with the help of appropriate
      contextual and semantic information of both models. Moreover, the semantic-based
      methods provide a means of validating and disambiguating the resulting bindings.
      Therefore, this work is a step forward to reduce the human participation in the
      mapping process.

PMID- 22421521
TI  - Progression of chronic subdural haematomas in an infant boy after abusive head
      trauma.
AB  - Abusive head trauma is a serious form of child abuse that can lead to severe
      neuropsychological sequelae or death in infants. In questionable cases, without a
      confession from the caregivers and ambiguous clinical information, evidence for
      the diagnosis of abusive head trauma is often based on typical patterns that have
      been observed in neuro-imaging. This study shows the progressive evolution of
      multifocal chronic subdural haematomas, including re-bleedings, in a case of
      abusive head trauma in an infant boy who was documented with repeated magnetic
      resonance imaging. The chronic subdural haematomas occurred during closely
      monitored in-patient rehabilitative care, and repeated maltreatment did not
      appear to be likely. Due to excessive growth, neurosurgical intervention with
      endoscopic craniotomy, evacuation of the subdural haematomas and temporal
      external cerebrospinal fluid drainage was performed with a favourable recovery.
      This study discusses the current pathophysiological knowledge concerning the
      development and clinical course of chronic subdural haematomas and draws relevant
      conclusions for the clinical practice and psychosocial management of caring for
      victims of abusive head trauma.

PMID- 22421522
TI  - Chronic cough with limited response to treatment and incidence of
      gastroesophageal reflux.
AB  - Our objective was to evaluate the association between chronic cough and the
      variables that could influence the course of the cough in order to develop a
      profile for coughers with poor response to treatment. In our Chronic Cough Unit,
      192 patients were prospectively followed up for 3 months, during which time all
      the variables that could influence the cough reflex were evaluated and treated.
      The improvement in cough was evaluated by the response of the patients to a
      visual analogical scale with scores from 0 to 4, considering 0 as "no changes"
      and an improvement as a score of 3 or 4. The cough was considered to have little
      response to treatment if it persisted without any improvement for more than 3
      months. Using a multivariate logistic regression model, we input variables that
      were candidates for being associated with the improvement in cough 3 months
      later. In the final profile model of the cougher with poor prognosis, three
      variables remained: sex, typical gastroesophageal reflux and psychosocial
      disorder. Being male is associated with an improvement in cough 3 months later
      (OR=2.10, 95%CI 1.00-4.38). However, having gastroesophageal reflux is associated
      with a reduction in the improvement three months later in 55% (OR=0.45, 95%CI
      0.24-0.84), and having a psychosocial disorder reduces the probability for
      improvement of the cough 3 months later in 70% (OR=0.30, 95%CI 0.09-1.03).

PMID- 22421523
TI  - Use of the electronic nose for diagnosing respiratory diseases.

PMID- 22421524
TI  - Genetic testing of candidate genes in arrhythmogenic right ventricular
      cardiomyopathy/dysplasia.
AB  - Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a rare
      cardiac genetic disease characterized by the presence of structural alterations
      in the right ventricle which may cause ventricular arrhythmias and may induce
      sudden cardiac death. ARVC/D has been associated with mutations in genes encoding
      myocyte adhesion proteins. However, only 30%-50% of patients have mutations in
      these genes. Genetic testing is useful in obtaining a diagnosis, particularly in
      individuals who do not completely fulfill clinical criteria, thereby also
      enabling the undertaking of preventive strategies in family members. The main
      goal of this study was to identify mutations in candidate genes associated with
      intercalate disks that could be potentially involved in ARVC/D pathogenesis. We
      analyze a cohort of 14 Spanish unrelated patients clinically diagnosed with
      ARVC/D without any genetic alteration in all previously known responsible genes.
      Thus, a genetic screening has been performed in 7 additional potential candidate
      genes (ACTC1 -actin alpha cardiac muscle 1-, CDHN -cadherin 2 type 1 or N
      cadherin-, CTNNA1 -catenin alpha 1-, Cx43 or GJA1 -gap junction protein alpha 1-,
      MVCL -Metavinculin-, MYL2 -myosin light chain 2- and MYL3 -myosin light chain 3-)
      by direct sequencing analysis. Our genetic analysis did not identify any disease
      causing mutation. Thirty single nucleotides polymorphisms were found, six of them
      novel. In conclusion, our ARVC/D Spanish cohort has not shown any mutations in
      the analyzed candidate genes despite their involvement in formation and
      maintenance of the intercalated disk.

PMID- 22421525
TI  - Subspace electrode selection methodology for the reduction of the effect of
      uncertain conductivity values in the EEG dipole localization: a simulation study
      using a patient-specific head model.
AB  - The simulation of the electroencephalogram (EEG) using a realistic head model
      needs the correct conductivity values of several tissues. However, these values
      are not precisely known and have an influence on the accuracy of the EEG source
      analysis problem. This paper presents a novel numerical methodology for the
      increase of accuracy of the EEG dipole source localization problem. The presented
      subspace electrode selection (SES) methodology is able to limit the effect of
      uncertain conductivity values on the solution of the EEG inverse problem,
      yielding improved source localization accuracy. We redefine the traditional cost
      function associated with the EEG inverse problem and introduce a selection
      procedure of EEG potentials. In each iteration of the presented EEG cost function
      minimization procedure, potentials are selected that are affected as little as
      possible by the uncertain conductivity value. Using simulation data, the proposed
      SES methodology is able to enhance the neural source localization accuracy
      dependent on the dipole location, the assumed versus actual conductivity and the
      possible noise in measurements.

PMID- 22421526
TI  - Obstetric decision-making and the late and moderately preterm infant.
AB  - The decision of when to deliver a patient for medical or obstetric complication
      directly affects the neonatal outcome. When the fetus is in danger due to
      suspected utero-placental insufficiency, the decision to deliver is thought to
      benefit the neonate. However, the opposite may be true when a normally developing
      fetus needs to be delivered for a maternal indication such as a persistently
      bleeding placenta praevia. These decisions are made daily by obstetric providers.
      The following is a review of obstetric decision-making for moderate and late
      preterm pregnancies.

PMID- 22421527
TI  - Biology and management of transient abnormal myelopoiesis (TAM) in children with
      Down syndrome.
AB  - Children with Down syndrome (DS) have an increased risk of Acute Myeloid
      Leukaemia (ML-DS), particularly megakaryoblastic leukaemia, which is clonally 
      related to the neonatal myeloproliferative syndrome, Transient Abnormal
      Myelopoiesis (TAM) unique to infants with DS. Molecular, biological, and clinical
      data indicate that TAM is initiated before birth when fetal liver haematopoietic
      cells trisomic for chromosome 21 acquire mutations in GATA1. TAM usually resolves
      spontaneously by 6 months; however 20-30% subsequently develop ML-DS harbouring
      the same GATA1 mutation(s). This review focuses on recent studies describing
      haematological, clinical and biological features of TAM and discusses approaches
      to diagnose, treat and monitor minimal residual disease in TAM. An important
      unanswered question is whether ML-DS is always preceded by TAM as it may be
      clinically and possibly haematologically 'silent'. We have briefly discussed the
      role of population-based screening for TAM and development of treatment
      strategies to eliminate the preleukaemic TAM clone, thereby preventing ML-DS.

PMID- 22421528
TI  - Effects of yokukansan on behavioral and psychological symptoms of vascular
      dementia: an open-label trial.
AB  - Previous clinical trials suggest that the traditional Japanese medicine
      yokukansan has beneficial effects on the behavioral and psychological symptoms of
      dementia (BPSD). The present study was conducted to elucidate the efficacy of
      yokukansan on BPSD in patients with vascular dementia. Thirteen Japanese patients
      (9 men and 4 women) who were diagnosed as having vascular dementia (VaD)
      according to the diagnostic criteria of NINDS-AIREN were subjected to the open
      label clinical trial in which yokukansan (7.5g/day) has been given for 4 weeks.
      Their mean age was 71.2+/-6.5 years. The BPSD was evaluated using the
      Neuropsychiatric Inventory (NPI), cognitive function was evaluated by the Mini
      Mental State Examination (MMSE), the activities of daily living was evaluated by
      Barthel index (BI) and Disability Assessment for Dementia (DAD), and the
      extrapyramidal signs were evaluated by United Parkinson's Disease Rating Scale
      (UPDRS). The mean NPI was 33.0+/-17.3 and 23.6+/-13.9 for the baseline and after
      treatment, respectively. It was significantly improved after treatment (p<0.05).
      In the NPI-subcategories, there was a significant improvement in agitation and
      disinhibition after the treatment. There was no significant change in MMSE, BI,
      DAD or UPDRS before and after the treatment. There was no adverse effect during
      the treatment period. The present results suggest that yokukansan is beneficial
      for the treatment of BPSD in VaD patients.

PMID- 22421529
TI  - Cannabis exposure associated with weight reduction and beta-cell protection in an
      obese rat model.
AB  - The aim of this study was to investigate the effect of an organic cannabis
      extract on beta-cell secretory function in an in vivo diet-induced obese rat
      model and determine the associated molecular changes within pancreatic tissue.
      Diet-induced obese Wistar rats and rats fed on standard pellets were
      subcutaneously injected with an organic cannabis extract or the vehicle over a 28
      day period. The effect of diet and treatment was evaluated using the
      intraperitoneal glucose tolerance tests (IPGTTs) and qPCR analysis on rat
      pancreata harvested upon termination of the experiment. The cafeteria diet
      induced an average weight difference of 32g and an overall increase in body
      weight in the experimental groups occurred at a significantly slower rate than
      the control groups, irrespective of diet. Area under the curve for glucose
      (AUC(g)) in the obese group was significantly lower compared to the lean group
      (p<0.001), with cannabis treatment significantly reducing the AUC(g) in the lean
      group (p<0.05), and remained unchanged in the obese group, relative to the obese
      control group. qPCR analysis showed that the cafeteria diet induced down
      regulation of the following genes in the obese control group, relative to lean
      controls: UCP2, c-MYC and FLIP. Cannabis treatment in the obese group resulted in
      up-regulation of CB1, GLUT2, UCP2 and PKB, relative to the obese control group,
      while c-MYC levels were down-regulated, relative to the lean control group.
      Treatment did not significantly change gene expression in the lean group. These
      results suggest that the cannabis extract protects pancreatic islets against the
      negative effects of obesity.

PMID- 22421530
TI  - Risk factors for surgical site infections after breast surgery: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Breast surgical site infections (SSIs) are major sources of
      postoperative morbidity and mortality, and it's established that surveillance of
      risk factors is effective in reducing hospital-acquired infections. However,
      studies about risk factors for breast SSIs were still under controversy because
      of limited data, contradictory results and lack of uniformity. MATERIALS AND
      METHODS: We searched the electronic database of PubMed for case-control studies
      about risk factors for breast SSIs, and a meta-analysis was conducted. RESULTS:
      Eight studies including 681 cases and 2064 controls were eligible, and data was
      combined if the risk factor was studied by at least two studies. Of the 20
      possible risk factors involved, 14 were proved significant for SSIs as follows:
      increased age, hypertension, higher body mass index (BMI), diabetes mellitus,
      American society of anesthesiologists (ASA) 3 or 4, previous breast biopsy or
      operation, preoperative chemoradiation, conservation therapy versus other
      surgical approaches, hematoma, seroma, more intraoperative bleeding,
      postoperative drain, longer drainage time and second drainage tube placed.
      However, other factors like smoking habit, immediate reconstruction, axillary
      lymph node dissection, preoperative chemotherapy, corticosteroid usage and
      prophylactic antibiotic didn't show statistical significance. CONCLUSIONS: This
      meta-analysis provided a list of predictable or preventable factors that could be
      taken measures to reduce the rate of breast SSIs and excluded some negligible
      factors. This could be useful for developing effective prevention and treatment
      policies for patients with SSIs and improving the overall quality of life.

PMID- 22421531
TI  - Combined excitotoxic-oxidative stress and the concept of non-cell autonomous
      pathology of ALS: insights into motoneuron axonopathy and astrogliosis.
AB  - Non-cell autonomous pathology is widely accepted to determine the demise of
      motoneurons (MNs) in amyotrophic lateral sclerosis (ALS) with astrocytes, GFAP
      and glutamate transport suggested to play roles in reactive astrogliosis.
      Previously we described actions of excitotoxicity and oxidative stress to produce
      differential injury of motoneurons and astrocytes, respectively, and our goal
      here was to define patterns of MN injury and astrogliosis during a combined
      excitotoxic-oxidative injury since such a paradigm more closely models disease
      pathology. Using an in vitro neuronal-glial culture of embryonic mouse spinal
      cord, we demonstrate that glutamate transport activity was maintained or
      increased initially, despite a loss of cellular viability, induced by exposure to
      combinations of excitotoxic [(S)-5-fluorowillardiine (FW)] and oxidative [3
      morpholinosydnonimine (SIN-1)] insults over 48 h. Under these conditions, injury
      was slow in time course and apoptotic-like as shown by the patterns of annexin V
      and propidium iodide (PI) labelling. Immunocytochemistry for SMI-32 revealed that
      injury produced time- and insult-dependent reductions in the size of MN arbours,
      axonal dieback and appreciable neuritic blebbing. These changes were preceded by
      early hypertrophy of GFAP-positive astrocytes, and followed by more delayed
      stellation and eventual gliotoxicity. Alterations to EAAT2 immunolabelling were
      similar to those found for GFAP being initially maintained and then eventually
      reduced at 48 h. Image analysis of immunocytochemical data confirmed the
      differential time-dependent changes found with SMI-32, GFAP and EAAT2. Axonopathy
      and blebbing of MNs was frequently associated with areas of low GFAP
      immunoreactivity. The exact profile of changes to MNs and astrocytes was context
      dependent and sensitive to subtle changes in the mix of excitotoxic-oxidative
      insults. Overall our findings are consistent with the concepts that the nature,
      extent and time-course of astrogliosis are insult-dependent, and that discrete
      pro-survival and destructive components of astrogliosis are likely to determine
      the precise profile of MN injury in non-cell autonomous pathology of ALS.

PMID- 22421532
TI  - Polycation-mediated enhancement of retroviral transduction efficiency depends on
      target cell types and pseudotyped Env proteins: implication for gene transfer
      into neural stem cells.
AB  - Polycations such as polybrene (PB) are routinely used for most retroviral vector
      mediated gene transfer studies because they can increase the infectivity of
      retroviruses. However, it was not systematically determined if addition of the
      polycation is an essential prerequisite for all retroviral transductions. To test
      this, we measured the effects of the polycation on transduction efficiency using
      various combinations of target cells and pseudotyped viral envelope (Env)
      proteins. Here, we show polycations do not always increase retroviral
      transduction efficiency and that their enhancing effect depends on both the type
      of target cells and Env proteins. The findings presented here also suggest that
      high transduction rates can be achieved in primary neural stem cells in vitro and
      in vivo by choosing an appropriate Env protein for pseudotyping without using
      polycations which are potentially toxic to primary cells and may change the
      intrinsic characteristics of cells.

PMID- 22421533
TI  - Cuprizone-induced demyelination in the rat cerebral cortex and thyroid hormone
      effects on cortical remyelination.
AB  - Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the Central
      Nervous System which is characterized by multifocal demyelinated lesions
      dispersed throughout the brain. Although white matter lesions have been the most
      extensively studied, cortical demyelinaton lesions are also detected in MS
      brains. Cuprizone (CPZ)-induced demyelination in rodents has been widely used as
      a model for MS. Most of these studies focus on oligodendrocyte-rich structures,
      such as the corpus callosum (CC) and the cerebellar peduncles. However, it has
      been recently described that CPZ administration in mice also produces cortical
      demyelination, resembling some of the lesions found in MS patients. In this work
      we used CPZ-demyelinating model in Wistar rats to study demyelination in cortical
      forebrain areas. At the ultrastructural level, demyelination in the cortex was
      observed before detectable myelin loss in the subcortical white matter. During
      the course of CPZ intoxication Myelin Basic Protein immunodetection was decreased
      in cortical layers I-III due to a reduction in the number of cortical
      oligodendrocytes (OL). Oligodendroglial loss in CPZ-intoxicated rats correlated
      with an increase in the number of Glial Fibrillary Acidic Protein positive
      astrocytes and a shift in the location of Carbonic Anhydrase II from OL to
      astrocytes. After removal of CPZ from the diet, we evaluate intranasal Thyroid
      hormone (TH) effects on the progression of cortical lesions. As previously
      reported in the CC, TH treatment also accelerates remyelination rate in the
      cortex compared to rats undergoing spontaneous remyelination. Our results suggest
      that manipulation of TH levels could be considered as a strategy to promote
      remyelination process in the cortex and to prevent neuronal irreversible damage
      in patients suffering from MS.

PMID- 22421534
TI  - Ammonium chloride influences in vitro-neuronal network activity.
AB  - The objective of the present work is to image functional alterations in hepatic
      encephalopathy (HE) by ammonia-induced changes of in vitro-neuronal network
      activity and to identify counteracting strategies. Synchronous bursting behavior
      of rat cortical cells which is the result of synaptic interaction of excitatory
      and inhibitory neurons was recorded in vitro on microelectrode arrays (MEAs)
      after ammonium chloride exposure. In order to test the involvement of astrocytic
      glutamine metabolism and N-methyl-d-aspartic acid- (NMDA-) receptor function in
      the observed ammonia-induced network dysregulation and to identify potentially
      protective strategies, we investigated effects of the glutamine synthetase (GS)
      inhibitor methionine-sulfoximine (MSO) and the NMDA-receptor antagonist DL-2
      Amino-5-phosphono-pentanoic acid (AP-5), respectively. We observed a
      characteristic ammonia-induced increase of global network activity while network
      synchrony was suppressed. The increase of global activity, but not the
      suppression of network synchrony was prevented by inhibiting GS. However,
      blocking NMDA-receptors prevented both, network excitation and desynchronization.
      CONCLUSIONS: 1. The observed desynchronization of in vitro-neuronal network
      activity after ammonium chloride treatment might reflect global neuronal network
      changes in HE in vivo and suggests the MEA technology as a valuable tool for
      measuring changes of neuronal connectivity in vitro. 2. Astrocytic glutamine
      metabolism might be involved in increased global network activity, but not in the
      suppression of network synchrony. 3. Overactivation of NMDA-receptors might
      underlie both, the ammonia-induced increase of activity and suppression of
      network synchrony, suggesting that NMDA-receptor function is involved in HE and
      that their blockage might be protective. 4. Measuring neuronal network activity
      in vitro by the MEA technology might help to describe functionally protective
      measures in HE.

PMID- 22421535
TI  - Quantitative determination of IgM antibodies reduces the pitfalls in the
      serodiagnosis of tick-borne encephalitis.
AB  - BACKGROUND: Tick-borne encephalitis (TBE) is the most important arbovirus disease
      in parts of Europe and Asia. Its laboratory diagnosis depends on the detection of
      specific IgM antibodies which can be impeded by (1) long-time persistence of IgM
      antibodies after infection, (2) vaccine-induced IgM antibodies, and (3) cross
      reactive IgM antibodies from other flavivirus infections. OBJECTIVES: To assess
      the extent of interference factors in the serodiagnosis of TBE that might lead to
      the false positive assignment of a recent infection. STUDY DESIGN: We quantified
      TBE virus-specific IgM and IgG antibodies in sera collected at different time
      points from cohorts of (1) 61 TBE patients, (2) 131 TBE vaccinees, and (3) 42
      patients with recent dengue or West Nile virus infections. RESULTS: All of the
      TBE patients were IgM- and IgG-positive upon hospitalization and 87% of acute TBE
      sera had IgM antibody titers of >500 Arbitrary Units (AU). These titers rapidly
      declined and only 16% of TBE patients had low IgM titers >=9 months after
      infection. Vaccine-induced as well as flavivirus cross-reactive IgM antibodies
      were rarely detectable and of low titer. CONCLUSIONS: Most of the potential
      problems of TBE serodiagnosis can be resolved by the quantification of IgM
      antibodies in a single serum sample taken upon hospitalization. High IgM values
      (>500 AU in our assay) are indicative of a recent infection. Lower IgM values,
      however, may require the analysis of a follow-up sample and/or a specific
      neutralization assay to exclude the possibilities of IgM persistence, vaccine
      induced IgM antibodies or heterologous flavivirus infections.

PMID- 22421536
TI  - A dilemma in management of an unwell infant: short term mortality vs. long term
      morbidity.

PMID- 22421537
TI  - Urine viral load and correlation with disease severity in infants with congenital
      or postnatal cytomegalovirus infection.
AB  - BACKGROUND: A correlation between cytomegalovirus (CMV) load in urine and
      severity of disease in congenitally infected infants has previously been
      reported. CMV load in postnatally infected infants has not been studied before.
      OBJECTIVE: To investigate CMV load in urine of infants with postnatal or
      congenital infection and correlate this with clinical symptoms of CMV disease and
      cerebral abnormalities. STUDY DESIGN: Infants admitted to our NICU between July
      2000 and February 2010, and diagnosed with congenital or postnatal CMV infection
      were included. Clinical symptoms of CMV infection, cranial ultrasonography (cUS)
      and magnetic resonance imaging (MRI) findings were evaluated. CMV urine loads of
      postnatally infected infants were analyzed and compared with CMV urine loads of
      congenitally infected infants. RESULTS: Seventeen infants with congenital CMV
      infection and 45 infants with postnatal CMV infection were included. Thirteen/17
      (76%) congenitally infected infants had clinical symptoms of CMV infection at
      birth and 11/17 (65%) had cerebral abnormalities diagnosed by neuro-imaging. None
      of the four asymptomatic infants had cerebral abnormalities. Of the postnatally
      infected infants 43/45 (96%) did not develop any clinical symptoms of CMV
      infection, but in 23/45 (51%) cerebral abnormalities such as lenticulostriate
      vasculopathy and germinolytic cysts were identified. The median CMV load in
      postnatally infected infants was significantly lower than in congenitally
      infected infants (1.0*10(5)copies/ml versus 8.5*10(6)copies/ml, p<0.001,
      respectively). CONCLUSIONS: CMV load in urine is significantly lower in infants
      with postnatal CMV infection than in infants with congenital CMV infection
      irrespective of clinical symptoms of CMV infection or cerebral abnormalities.

PMID- 22421538
TI  - Plasmacytoid dendritic cell depletion leads to an enhanced mononuclear phagocyte
      response in lungs of mice with lethal influenza virus infection.
AB  - Plasmacytoid dendritic cells (pDCs) have been implicated both in the control and
      pathogenesis of influenza virus infection. We demonstrate that pDC depletion has
      marked effects on the response of mononuclear phagocytes, including conventional
      DCs (cDCs) and macrophages, to lethal influenza virus infection. Infection of
      mice lacking pDCs through antibody-mediated depletion resulted in substantially
      increased accumulation of mononuclear phagocytes and their progenitors in lungs
      compared to non-treated controls. pDC ablation resulted in a 5- to 35-fold
      enhancement of intracellular TNF-alpha and IL-6 production from inflammatory cDCs
      and exudate macrophages. Purified pulmonary cDCs and macrophages cultured from
      pDC-depleted mice produced significantly elevated levels of pro-inflammatory
      cytokines and chemokines compared to pDC-intact counterparts. Elimination of pDCs
      resulted in decreased lung IFN-alpha production and an immediate and transient
      reduction in lung virus burden but did not impact disease outcome. These data
      reveal a suppressive effect of pDCs on the inflammatory response to influenza
      virus infection in the lung.

PMID- 22421539
TI  - Binomial regression with a misclassified covariate and outcome.
AB  - Misclassification occurring in either outcome variables or categorical covariates
      or both is a common issue in medical science. It leads to biased results and
      distorted disease-exposure relationships. Moreover, it is often of clinical
      interest to obtain the estimates of sensitivity and specificity of some
      diagnostic methods even when neither gold standard nor prior knowledge about the
      parameters exists. We present a novel Bayesian approach in binomial regression
      when both the outcome variable and one binary covariate are subject to
      misclassification. Extensive simulation results under various scenarios and a
      real clinical example are given to illustrate the proposed approach. This
      approach is motivated and applied to a dataset from the Baylor Alzheimer's
      Disease and Memory Disorders Center. 

PMID- 22421540
TI  - Mitochondrial translational inhibitors in the pharmacopeia.
AB  - The vast majority of energy necessary for cellular function is produced in the
      mitochondria by the phosphorylation of ADP to ATP. Other critical mitochondrial
      functions include apoptosis and free-radical production. Chemical agents,
      including those found in the modern pharmacopeia, may impair mitochondrial
      function by a number of mechanisms. The mitochondria are vulnerable to
      environmental injury because of their complex physical structure, electrochemical
      properties of the inner mitochondrial membrane (IMM), dual genetic control from
      both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) and inherent properties of
      the translational and transcriptional machinery. Mitochondria have evolved from
      alpha-proteobacteria and the residual structural similarity to bacterial
      translational machinery has left the mtDNA genes vulnerable to inhibition by
      commonly used translation-targeted antibiotics. Many of these medications cause
      adverse effects in otherwise healthy people, but there are also examples where
      particular gene mutations may predispose to increased drug toxicity. It is hoped
      that preclinical pharmacogenetic and functional studies of mitochondrial
      toxicity, along with personalized genomic medicine, will improve both our
      understanding of the spectrum of disease caused by inhibition of mitochondrial
      translation and improve the safe and effective use of antibiotics that inhibit
      bacterial and human mitochondrial translation. This article is part of a Special
      Issue entitled: Mitochondrial Gene Expression.

PMID- 22421541
TI  - Multidisciplinary consultation within a paediatric medical setting: a personal
      view.

PMID- 22421542
TI  - Determining reactive hyperaemia time in deep inferior epigastric perforators
      after temporary occlusion to allow the intraoperative comparison of vascular
      territories.

PMID- 22421543
TI  - Denis F. Keegan: forgotten pioneer of plastic surgery.

PMID- 22421544
TI  - Ultraviolet Resonance Raman spectroscopy used to study formulations of salmon
      calcitonin, a starch-peptide conjugate and TGF-beta3.
AB  - Ultraviolet Resonance Raman (UVRR) spectroscopy with excitation at 244 nm was
      investigated here as a possible useful tool for fast characterization of
      biopharmaceuticals. Studies were performed on three protein drugs: salmon
      calcitonin (sCT), starch-peptide conjugate, and transforming growth factor-beta3
      (TGF-beta3) adsorbed onto solid granules of tricalcium phosphate (TCP). Secondary
      structure of sCT was investigated for solutions of 0.5mg/mL up to 200mg/mL,
      regardless of the turbidity or aggregation states. An increase in beta-sheet
      content was detected when sCT solutions aggregated. UVRR spectroscopy also
      detected a small amount of residual organic solvent in a starch-peptide conjugate
      solution containing only 40 MUg/mL of peptide. UVRR spectroscopy was then used to
      characterize a protein, TGF-beta3, adsorbed onto solid granules of TCP at 50 and
      250 MUg/cm(3). This study shows that UVRR is suitable to characterize the protein
      formulations in a broad range of concentrations, in liquid, aggregated, and solid
      states.

PMID- 22421545
TI  - H2B monoubiquitylation is a 5'-enriched active transcription mark and correlates
      with exon-intron structure in human cells.
AB  - H2B monoubiquitylation (H2Bub1), which is required for multiple methylations of
      both H3K4 and H3K79, has been implicated in gene expression in numerous organisms
      ranging from yeast to human. However, the molecular crosstalk between H2Bub1 and
      other modifications, especially the methylations of H3K4 and H3K79, remains
      unclear in vertebrates. To better understand the functional role of H2Bub1, we
      measured genome-wide histone modification patterns in human cells. Our results
      suggest that H2Bub1 has dual roles, one that is H3 methylation dependent, and
      another that is H3 methylation independent. First, H2Bub1 is a 5'-enriched active
      transcription mark and co-occupies with H3K79 methylations in actively
      transcribed regions. Second, this study shows for the first time that H2Bub1
      plays a histone H3 methylations-independent role in chromatin architecture.
      Furthermore, the results of this work indicate that H2Bub1 is largely positioned
      at the exon-intron boundaries of highly expressed exons, and it demonstrates
      increased occupancy in skipped exons compared with flanking exons in the human
      and mouse genomes. Our findings collectively suggest that a potentiating
      mechanism links H2Bub1 to both H3K79 methylations in actively transcribed regions
      and the exon-intron structure of highly expressed exons via the regulation of
      nucleosome dynamics during transcription elongation.

PMID- 22421546
TI  - Chromatin state signatures associated with tissue-specific gene expression and
      enhancer activity in the embryonic limb.
AB  - The regulatory elements that direct tissue-specific gene expression in the
      developing mammalian embryo remain largely unknown. Although chromatin profiling
      has proven to be a powerful method for mapping regulatory sequences in cultured
      cells, chromatin states characteristic of active developmental enhancers have not
      been directly identified in embryonic tissues. Here we use whole-transcriptome
      analysis coupled with genome-wide profiling of H3K27ac and H3K27me3 to map
      chromatin states and enhancers in mouse embryonic forelimb and hindlimb. We show
      that gene-expression differences between forelimb and hindlimb, and between limb
      and other embryonic cell types, are correlated with tissue-specific H3K27ac
      signatures at promoters and distal sites. Using H3K27ac profiles, we identified
      28,377 putative enhancers, many of which are likely to be limb specific based on
      strong enrichment near genes highly expressed in the limb and comparisons with
      tissue-specific EP300 sites and known enhancers. We describe a chromatin state
      signature associated with active developmental enhancers, defined by high levels
      of H3K27ac marking, nucleosome displacement, hypersensitivity to sonication, and
      strong depletion of H3K27me3. We also find that some developmental enhancers
      exhibit components of this signature, including hypersensitivity, H3K27ac
      enrichment, and H3K27me3 depletion, at lower levels in tissues in which they are
      not active. Our results establish histone modification profiling as a tool for
      developmental enhancer discovery, and suggest that enhancers maintain an open
      chromatin state in multiple embryonic tissues independent of their activity
      level.

PMID- 22421547
TI  - Prevalence and determinants of coronary artery disease in first-degree relatives
      of premature coronary artery disease.
AB  - BACKGROUND: This study aimed to investigate the prevalence of subclinical
      coronary artery disease (CAD) in first-degree relatives (FDRs) with premature CAD
      and its associating factors other than conventional risk factors. METHODS: A
      total of 122 FDRs (58 men, 50+/-7 years) of patients with premature CAD were
      enrolled. The individuals who had undergone health checkups were included in the
      control group. Multidetector coronary computed tomography was performed to detect
      subclinical CAD. RESULTS: The prevalence of subclinical CAD (35 vs. 14%, P<0.001)
      and at least 50% subclinical CAD (16 vs. 2.5%, P<0.001) was higher in FDRs than
      that in the control group. In conditional regression analysis, the urinary
      albumin-creatinine ratio showed a significant interaction with CAD in FDRs than
      the control (odds ratio 1.063, 95% confidence interval 1.009-1.118, P=0.021).
      CONCLUSION: FDRs of premature CAD are more prevalent in subclinical CAD
      independent of conventional risk factors. Urinary albumin-creatinine ratio may
      have an interaction with the development of subclinical CAD in FDRs of premature
      CAD.

PMID- 22421548
TI  - Identification of residual risk factors for the development of venous
      thromboembolism in medical inpatients receiving subcutaneous heparin therapy for
      prophylaxis.
AB  - OBJECTIVES: Venous thromboembolism (VTE) such as pulmonary embolism and deep
      venous thrombosis is the most common cause of preventable morbidity and mortality
      in hospitalized patients. Prophylaxis is recommended for medical patients older
      than 40 years with at least one risk factor. However, the currently recommended
      regimen prevents only about half of in-hospital VTE. The aim of this study was to
      identify the risk factors for development of VTE in medical inpatients who were
      already on recommended pharmacological prophylaxis. METHODS: We performed a
      retrospective cohort study of 10,633 patients who were admitted to the medicine
      service and received prophylaxis with subcutaneous unfractionated heparin. The
      diagnoses of pulmonary embolism and deep venous thrombosis were confirmed with
      computed tomography angiography and Doppler ultrasound, respectively. Univariate
      analysis with the chi(2)-test, followed by log-linear Poisson regression analysis
      was performed to determine the relative risk associated with each factor.
      RESULTS: Sixty cases of in-hospital VTE [raw incidence, 0.6%; 95% confidence
      interval (0.43-0.72)] were observed. On univariate analysis, a previous history
      of VTE or an active malignancy were found to be significant residual risk factors
      for the development of in-hospital VTE. On multivariate analysis, only a previous
      history of VTE remained a significant independent risk factor [relative
      risk=30.1; 95% confidence interval (17.1-53.0); P<0.0001]. CONCLUSION: Among
      hospitalized patients admitted to the medicine service and receiving VTE
      prophylaxis with subcutaneous unfractionated heparin, those with a previous
      history of VTE were at a significant risk of developing in-hospital VTE. This at
      risk population should be considered for more aggressive therapy to prevent
      recurrent VTE.

PMID- 22421549
TI  - Ischemic postconditioning through percutaneous transluminal coronary angioplasty
      in pigs:  roles of PI3K activation.
AB  - BACKGROUND: Ischemic postconditioning (IPOC) has been suggested to reduce
      ischemic reperfusion injury. It remains unclear whether the activation of
      phosphatidylinositol 3 kinase (PI3K)/Akt is a causal mechanism in the
      cardioprotection afforded by IPOC, which was examined in the model of
      percutaneous transluminal coronary angioplasty (PTCA) minipigs. METHODS AND
      RESULTS: Minipigs underwent 45-min occlusion of the left anterior descending
      artery and 24-h reperfusion by PTCA. Postconditioning was elicited by three
      cycles of 30-s reperfusion followed by 30-s ischemia at the onset of reperfusion.
      Infarct size was determined by triphenyl tetrazolium chloride staining after 24-h
      reperfusion, and mRNA and protein expression levels of PI3K were ascertained by
      reverse transcriptase-PCR and western-blot analysis in biopsies. Infarct size was
      significantly reduced and myocardial PI3K (Akt and GSK-3beta) phosphorylation was
      significantly increased with IPOC treatment compared with ischemic reperfusion.
      The administration of the PI3K inhibitor wortmannin (30 ug/kg) attenuated the
      protection of IPOC in the infarct size and decreased the expression of Akt and
      GSK-3beta phosphorylation compared with IPOC. IPOC had no impact on mRNA
      expression of AKT and GSK-3beta. CONCLUSION: Our findings show that IPOC is
      capable of protecting the myocardium against IR injury in the PTCA minipig model.
      The PI3K/Akt-signaling pathway is involved in the cardioprotective effect of
      IPOC.

PMID- 22421550
TI  - A critique of human rights based approaches should demonstrate an understanding
      of human rights based approaches.

PMID- 22421551
TI  - Global Fund investments in harm reduction from 2002 to 2009.
AB  - BACKGROUND: Injecting drug use has been documented in 158 countries and is a
      major contributor to HIV epidemics. People who inject drugs have poor and
      inequitable access to HIV services. The Global Fund to Fight AIDS, Tuberculosis
      and Malaria is the leading multilateral donor for HIV programmes and encourages
      applicants to include harm reduction interventions in their proposals. This study
      is the first detailed analysis of Global Fund investments in harm reduction
      interventions. METHODS: The full list of more than 1000 Global Fund grants was
      analysed to identify HIV grants that contain activities for people who inject
      drugs. Data were collected from the detailed budgets agreed between the Global
      Fund and grant recipients. Relevant budget lines were recorded and analysed in
      terms of the resources allocated to different interventions. RESULTS: 120 grants
      from 55 countries and territories contained activities for people who inject
      drugs worth a total of US$ 361 million, increasing to US$ 430 million after
      projections were made for grants that had yet to enter their final phase of
      funding. Two-thirds of the budgeted US$ 361 million was allocated to core harm
      reduction activities as defined by the United Nations. Thirty-nine of the 55
      countries were in Eastern Europe and Asia. Only three countries with generalised
      HIV epidemics had grants that included harm reduction activities. CONCLUSION:
      This study represents the most comprehensive assessment of Global Fund
      investments in harm reduction. This funding, while substantial, falls short of
      the estimated needs. Investments in harm reduction must increase if HIV
      transmission among people who inject drugs is to be halved by 2015.

PMID- 22421552
TI  - Drug treatment court of Vancouver: an empirical evaluation of recidivism.
AB  - BACKGROUND: Drug treatment courts (DTCs) have proliferated on the basis of their
      promise to reduce criminal recidivism among the burgeoning numbers of drug
      related offenders. Empirical research on the effectiveness of DTCs indicates that
      they produce reductions in recidivism, primarily drawn from experiences in the
      US. There are no published outcome studies on Canadian DTCs. Canada's second DTC
      has operated in Vancouver's Downtown Eastside since 2001. We examine longitudinal
      changes in recidivism and characteristics of participants in the DTC in Vancouver
      (DTCV). METHODS: DTCV participants (n=180) were included in a longitudinal cohort
      design (intent-to-treat), and a comparison group was derived using the propensity
      score matching method. Matching variables represented the domains of health,
      offending, and socio-economic histories as well as demographics. Annualized rates
      of offending were compared for the two years prior to entering DTCV and two years
      following programme termination. RESULTS: Compared to the matched group of
      offenders, DTCV participants exhibited significantly greater reductions in
      offending, and a significant decrease in drug-related offences. The
      characteristics of DTCV participants differ significantly from those of the
      larger offender population in the DTES. CONCLUSION: Results provide empirical
      support for the DTCV in relation to the goal of reducing criminal recidivism.
      Participants in the DTCV are disadvantaged in diverse ways apart from their
      offence-related difficulties. These results have implications for the design of
      DTC programmes, as well as for future research.

PMID- 22421553
TI  - Examination of the risk of reinfection with hepatitis C among injecting drug
      users who have been tested in Glasgow.
AB  - BACKGROUND: Unsafe injecting practices put injecting drug users (IDUs) at repeat
      exposure to infection with the hepatitis C virus (HCV). It has not yet been
      determined if spontaneously clearing one's primary infection influences the risk
      of reinfection; our aim was to estimate the relative risk of reinfection in IDUs
      who have cleared the virus. METHODS: We conducted a retrospective study using a
      large database of HCV test results covering Greater Glasgow Health Board during
      1993-2007 to calculate rates of infection and reinfection in current/former IDUs.
      The relative risk of (re)infection in previously infected compared with never
      infected IDUs was estimated using Poisson regression, adjusting for age at study
      entry, sex, and calendar period of test. RESULTS: Although the rate of
      reinfection in IDUs who were HCV antibody-positive, RNA-negative at baseline was
      lower (7/100 person-years, 95% CI: 5-9) than the rate of acute infection in IDUs
      who were HCV antibody-negative at baseline (10/100 person-years, 95% CI: 9-12),
      the risk of reinfection was not significantly different than the risk of initial
      infection (adjusted rate ratio=0.78, 95% CI: 0.57-1.08). CONCLUSION: We found
      only weak evidence for a reduced risk of HCV reinfection in IDUs who had cleared
      their previous infection. Further research among those who have cleared infection
      through antiviral therapy is needed to help inform decisions regarding treatment
      of IDUs.

PMID- 22421554
TI  - HCV seroconversion among never-injecting heroin users at baseline: no predictors
      identified other than starting injection.
AB  - BACKGROUND: Heroin users who do not inject constitute a large pool of drug users
      with a potentially important impact on public health. We aimed to estimate the
      incidence of hepatitis C virus (HCV) among heroin users who had never injected
      (NIDUS) at baseline, and the effect of starting injecting during follow-up, other
      percutaneous exposures, sharing snorting paraphernalia, cocaine/crack use, and
      risky sexual behaviour on HCV-seroconversion. METHODS: Prospective cohort of 305
      HCV-negative NIDUs at baseline, aged 18-30 and street-recruited in three Spanish
      cities in 2001-2003. Computer-assisted personal interviews were conducted and
      dried blood-spot samples were collected. Bivariate and multivariable Poisson
      models were used. RESULTS: Among the 305 never-injectors who were HCV-negative at
      baseline, 197 (64.6%) were followed-up and 21 seroconverted [HCV-incidence
      rate=5.8/100 person-years at risk (pyar) (95% CI: 3.6-8.9)]. HCV incidence in new
      injectors was 28.4/100 pyar [(95% CI, 14.7-49.7) vs. 2.8/100 pyar (95% CI, 1.3
      5.4)] among NIDUs. Of the risk exposures considered, starting injecting was the
      only predictor of HCV-seroconversion [adjusted relative risk=10.1, 95% CI: 3.8
      26.7]. CONCLUSION: The HCV-seroconversion rate was 10 times higher among new
      injectors than never-injectors. No predictors other than starting injecting were
      found for HCV-seroconversion. Harm reduction interventions to prevent HCV
      infection should include prevention of drug injection.

PMID- 22421555
TI  - Understanding the gendered patterns of substance use initiation among adolescents
      living in rural, central Mexico.
AB  - BACKGROUND: Little is known about the age of initiation and gender differences in
      substance use among adolescents in rural, central Mexico. METHODS: The cross
      sectional data were collected from students enrolled in the Videobachillerato
      (VIBA) (video high school) programme in Guanajuato, Mexico. Questionnaires asked
      students about the age at which they had used alcohol, cigarettes, or cannabis
      for the first time. Kaplan-Meier Survival Functions were used to estimate if
      males and females were significantly different in their cumulative probabilities
      of initiating substances over time. RESULTS: On average, alcohol is initiated at
      14.7 years of age, cigarettes at 15.1 years of age, and cannabis at 16.5 years of
      age. Over time, males had a significantly higher probability of initiating
      alcohol (Kaplan-Meier Failure Curve: X(2)=26.35, p<0.001), cigarettes (Kaplan
      Meier Failure Curve: X(2)=41.90, p<0.001), and cannabis (Kaplan-Meier Failure
      Curve: X(2)=38.01, p<0.001) compared to females. CONCLUSIONS: These results
      highlight the gendered patterns of substance use initiation among adolescents in
      rural, central Mexico and underscore the need for gendered substance use
      prevention interventions with these adolescents. By putting forth efforts to
      understand substance use initiation patterns of adolescents living in rural,
      central Mexico, culturally specific and efficacious prevention efforts can be
      tailor-made to create lasting differences.

PMID- 22421556
TI  - The gendered trouble with alcohol: young people managing alcohol related
      violence.
AB  - BACKGROUND: Alcohol related violence is a troubling backdrop to the social lives
      and relationships of many young people in post-industrial societies. The
      development of the night-time economy where young people are encouraged to drink
      heavily in entertainment precincts has increased the risk of violence. METHODS:
      This paper reports on 60 individual structured in-depth interviews about the
      drinking biographies of young people (aged 20-24) living in Victoria, Australia.
      Twenty-six males and 34 females participated in the research. The participants
      discussed their experiences with alcohol over their life course to date. The
      material on alcohol related violence is analysed in this paper. RESULTS: Just
      over half of the participants (33/60) recounted negative experiences with alcohol
      related violence. The findings demonstrate the continuing gendered nature of
      experiences of perpetration and victimization. Participants reported that
      aggression and violence perpetrated by some men was fuelled by alcohol
      consumption and required ongoing management. Experiences of violence were also
      spatialized. Men were more likely to report managing and avoiding violence in
      particular public settings whilst more women than men discussed managing violence
      in domestic settings. CONCLUSION: The central argument of this paper is that
      incidents of alcohol related violence and reactions to it are specific gender
      performances that occur in specific socio-cultural contexts. In contrast to
      research which has found some young people enjoy the adventure and excitement of
      alcohol related violence the mainstream participants in this study saw violence
      as a negative force to be managed and preferably avoided. Understanding violence
      as a dynamic gender performance complicates the development of policy measures
      designed to minimize harm but also offers a more holistic approach to developing
      effective policy in this domain. There is a need for greater acknowledgement that
      alcohol related violence in public venues and in families is primarily about
      particular performances of masculinity and this is where policy should be
      targeted in addition to venue based interventions.

PMID- 22421557
TI  - Hepatitis B vaccination of susceptible elderly residents of long term care
      facilities during a hepatitis B outbreak.
AB  - Protection of older persons, particularly those with diabetes, against hepatitis
      B virus (HBV) infection is of growing concern because of increased reports of
      outbreaks among long-term care facility residents receiving assisted blood
      glucose monitoring. We evaluated hepatitis B vaccine immunogenicity among
      residents immunized in response to two such outbreaks in skilled nursing
      facilities during June 2009-July 2010. One hundred forty-eight (71%) of 209
      residents were found to be susceptible to HBV infection. Of 105 patients who
      began a vaccination series with Twinrix((r)) (0-, 1-, 6-month dosing), 86 (82%)
      completed the series and postvaccination testing. Of these, most were elderly
      (median age 79.5 years; range 45-101), female (56%), and African-American (51%).
      Twenty-nine (34%) vaccinated residents had post-vaccination hepatitis B surface
      antibody levels >=10 mIU/ml. There were no significant differences in vaccine
      response by age, gender, race, diabetes status, body mass index, or current
      smoking status. Our findings indicate that a low proportion of skilled nursing
      facility residents achieved a seroprotective response after hepatitis B
      vaccination.

PMID- 22421558
TI  - Do the media provide transparent health information? A cross-cultural comparison
      of public information about the HPV vaccine.
AB  - The media is a powerful tool for informing the public about health treatments. In
      particular, the Internet has gained importance as a widely valued source for
      health information for parents and adolescents. Nonetheless, traditional sources,
      such as newspapers, continue to report on health innovations. But do websites and
      newspaper reports provide balanced information? We performed a systematic media
      analysis to evaluate and compare media coverage of the human papillomavirus (HPV)
      vaccine on websites and in newspapers in Germany and Spain. We assessed to what
      extent the media provide complete (pros and cons), transparent (absolute instead
      of relative numbers), and correct information about the epidemiology and etiology
      of cervical cancer as well as the effectiveness and costs of the HPV vaccine. As
      a basis for comparison, a facts box containing current scientific evidence about
      cervical cancer and the HPV vaccine was developed. The media analysis included 61
      websites and 141 newspaper articles in Germany, and 41 websites and 293 newspaper
      articles in Spain. Results show that 57% of German websites and 43% of German
      newspaper reports communicated correct estimates of epidemiological data, whereas
      in Spain 39% of the websites and 20% of the newspaper did so. While two thirds of
      Spanish websites explicitly mentioned causes of cervical cancer as well as
      spontaneous recovery, German websites communicated etiological information less
      frequently. Findings reveal that correct estimates about the vaccine's
      effectiveness were mentioned in 10% of German websites and 6% of German newspaper
      reports; none of the Spanish newspaper reports and 2% of Spanish websites
      reported effectiveness correctly. Only German websites (13%) explicitly referred
      to scientific uncertainty regarding the vaccine's evaluation. We conclude that
      the media lack balanced reporting on the dimensions completeness, transparency,
      and correctness. We propose standards for more balanced reporting on websites and
      in newspapers.

PMID- 22421560
TI  - NASPAG 25 years later.

PMID- 22421561
TI  - OHVIRA syndrome (obstructed hemivagina and ipsilateral renal anomaly) with uterus
      didelphys, an unusual presentation.
AB  - BACKGROUND: Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA), or
      Herlyn-Werner-Wunderlich syndrome, is a rare Mullerian duct anomaly with uterus
      didelphys, unilateral obstructed hemivagina, and ipsilateral renal agenesis.
      Patients with this anomaly usually present after menarche with pelvic pain and/or
      a mass and rarely, in later years, with primary infertility. Strong suspicion and
      knowledge of this anomaly are essential for a precise diagnosis. CASE: A 14-year
      old female presented with acute retention of urine and was diagnosed as a case of
      OHVIRA syndrome with uterus didelphys. Acute retention of urine as the initial
      clinical presentation has been rarely reported in this syndrome. She was treated
      with hemivaginal septal resection. SUMMARY AND CONCLUSION: OHVIRA syndrome should
      be considered among the differential diagnoses in young females with renal
      anomalies presenting with pelvic mass, symptoms of acute abdomen, and acute
      urinary retention.

PMID- 22421562
TI  - Associations between oxytocin receptor gene (OXTR) polymorphisms and self
      reported aggressive behavior and anger: Interactions with alcohol consumption.
AB  - Oxytocin has been implicated in the regulation of social as well as aggressive
      behaviors, and in a recent study we found that the effect of alcohol on
      aggressive behavior was moderated by the individual's genotype on an oxytocin
      receptor gene (OXTR) polymorphism (Johansson et al., 2012). In this study we
      wanted to deepen and expand the analysis by exploring associations between three
      (rs1488467, rs4564970, rs1042778) OXTR polymorphisms and aggressive behavior,
      trait anger as well as anger control in a population-based sample of Finnish men
      and women (N=3577) aged between 18 and 49 years (M=26.45 years, SD=5.02). A
      specific aim was to investigate if the polymorphisms would show interactive
      effects with alcohol consumption on aggressive behavior and trait anger, as well
      as to explore whether these polymorphisms affect differences in anger control
      between self-reported sober and intoxicated states. The results showed no main
      effects of the polymorphisms, however, three interactions between the
      polymorphisms and alcohol consumption were found. The effect of alcohol
      consumption on aggressive behavior was moderated by the genotype of the
      individual on the rs4564970 polymorphism, in line with previous results
      (Johansson et al., 2012). For trait anger, both the rs1488467 and the rs4564970
      polymorphisms interacted with alcohol consumption. It appears that the region of
      the OXTR gene including both the rs4564970 and the rs1488467 polymorphisms may be
      involved in the regulation of the relationship between alcohol and aggressive
      behavior as well as between alcohol and the propensity to react to situations
      with elevated levels of anger.

PMID- 22421563
TI  - Psychosocial animal model of PTSD produces a long-lasting traumatic memory, an
      increase in general anxiety and PTSD-like glucocorticoid abnormalities.
AB  - Post-traumatic stress disorder (PTSD) is characterized by a pathologically
      intense memory for a traumatic experience, persistent anxiety and physiological
      abnormalities, such as low baseline glucocorticoid levels and increased
      sensitivity to dexamethasone. We have addressed the hypothesis that rats
      subjected to chronic psychosocial stress would exhibit PTSD-like sequelae,
      including traumatic memory expression, increased anxiety and abnormal
      glucocorticoid responses. Adult male Sprague-Dawley rats were exposed to a cat on
      two occasions separated by 10 days, in conjunction with chronic social
      instability. Three weeks after the second cat exposure, the rats were tested for
      glucocorticoid abnormalities, general anxiety and their fear-conditioned memory
      of the two cat exposures. Stressed rats exhibited reduced basal glucocorticoid
      levels, increased glucocorticoid suppression following dexamethasone
      administration, heightened anxiety and a robust fear memory in response to cues
      that were paired with the two cat exposures. The commonalities in endocrine and
      behavioral measures between psychosocially stressed rats and traumatized people
      with PTSD provide the opportunity to explore mechanisms underlying psychological
      trauma-induced changes in neuroendocrine systems and cognition.

PMID- 22421564
TI  - Relation between anterior cruciate ligament graft obliquity and knee laxity in
      elite athletes at the National Football League combine.
AB  - PURPOSE: The purposes of this study were to determine the incidence of vertical
      anterior cruciate ligament (ACL) reconstructions in elite athletes and to
      determine whether graft obliquity correlates with knee stability in this
      population. METHODS: One hundred thirty-seven knees in 125 athletes at the 2005
      2009 National Football League Combine were identified as having had previous ACL
      reconstructions. The graft type, fixation, and physical examination findings were
      recorded for each athlete. Graft obliquity was measured by previously described
      methods based on plain radiography and magnetic resonance imaging (MRI).
      Radiographic measurements included tibial tunnel and femoral tunnel locations, as
      well as a sum of these tunnel positions on the lateral radiograph (sum score).
      MRI measurements included sagittal and coronal ACL angles and the ACL-Blumensaat
      line angle. The relation of graft obliquity to physical examination findings was
      assessed. RESULTS: Sixty-four percent of knees had vertical grafts based on
      radiography and 35% based on MRI criteria. The average tibial tunnel location on
      radiography was 33% from the anterior tibial plateau in the oblique group
      compared with 42% in the vertical group (P < .0001). Knees with a sum score of 66
      or less, tibial tunnel 37% or less from the anterior tibial plateau, and sagittal
      obliquity of 60 degrees  or less were less likely to have increased translation
      on the Lachman examination than knees with a sum score greater than 66, tibial
      tunnel greater than 37% from the anterior tibial plateau, and sagittal obliquity
      greater than 60 degrees  (P < .05). CONCLUSIONS: There was a wide range of ACL
      graft obliquity in the examined cohort of elite athletes who continued to perform
      at high levels. Less oblique (more vertical) grafts were associated with greater
      anterior tibial translation on Lachman testing. ACL graft obliquity, which is
      particularly sensitive to tibial tunnel placement, can influence knee stability.
      LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 22421565
TI  - Long-term results of anterior cruciate ligament reconstruction using bone
      patellar tendon-bone: an analysis of the factors affecting the development of
      osteoarthritis.
AB  - PURPOSE: To evaluate the clinical outcomes and incidence of knee osteoarthritis
      (OA) and the factors associated with the onset of OA in the 3 compartments of the
      knee joint separately after anterior cruciate ligament (ACL) reconstruction with
      bone-patellar tendon-bone autograft. METHODS: Clinical and radiologic assessments
      were obtained from 117 patients (80.1%). At follow-up, knee function was
      evaluated with the Lysholm score, Hospital for Special Surgery (HSS) score,
      Tegner score, and International Knee Documentation Committee (IKDC) 2000 forms.
      We also evaluated stability and donor-site morbidity. On the follow-up
      radiographs, OA was assessed by IKDC grading. The factors affecting the onset of
      OA in the 3 compartments of the knee joint were evaluated. RESULTS: The mean
      follow-up period was 10.3 +/- 1.0 years. The mean Lysholm and HSS scores
      significantly increased at final follow-up (P < .001). The mean IKDC subjective
      score was 90.6, and 93.9% of patients had grade A or grade B knees on the
      objective evaluation. The mean side-to-side difference measured by KT-2000
      arthrometer (MEDmetric, San Diego, CA) was 1.6 +/- 1.7 mm, with 82.0% of patients
      showing a difference of less than 3 mm. Discomfort from knee walking on hard
      ground and skin numbness were reported by 38.4% and 37.6% of patients,
      respectively. OA developed in the medial, lateral, and patellofemoral
      compartments in 30.7%, 9.3%, and 7.6% of patients, respectively. The onset of OA
      was associated with partial meniscectomy (odds ratio [OR], 20.73; P = .005) or
      sagittal tibial tunnel position (OR, 1.18; P = .02) in the medial compartment and
      body mass index (BMI) (OR, 1.56; P = .02) in the lateral compartment.
      CONCLUSIONS: ACL reconstruction with bone-patellar tendon-bone autograft showed
      satisfactory clinical results after a mean of 10.3 years. However, pain when
      walking on hard ground (38.4%) and numbness of the skin (37.6%) were reported.
      Moreover, the onset of OA appeared in over 40% of the patients. The onset of OA
      in the medial compartment was correlated with partial meniscectomy and sagittal
      tibial tunnel position, and the onset of OA in the lateral compartment was
      correlated with higher BMI. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 22421566
TI  - Is femoral tunnel length correlated with the intercondylar notch and femoral
      condyle geometry after double-bundle anterior cruciate ligament reconstruction
      using the transportal technique? An in vivo computed tomography analysis.
AB  - PURPOSE: To analyze femoral tunnel geometry using computed tomography (CT)
      imaging and evaluate the anatomic factors affecting femoral tunnel length after
      anterior cruciate ligament (ACL) reconstruction by the transportal technique.
      METHODS: Twenty-nine patients underwent an anatomic double-bundle ACL
      reconstruction with a femoral tunnel drill by the transportal technique. CT
      imaging with OsiriX software (version 3.8; Pixmeo, Geneva, Switzerland) was used
      to measure femoral tunnel length (anteromedial [AM], posterolateral [PL], and
      central), femoral tunnel divergent angle, and femoral condyle size and
      intercondylar notch size parameters. Correlations between femoral tunnel length
      and femoral condyle size and intercondylar notch size parameters were analyzed.
      RESULTS: The mean AM, PL, and central femoral tunnel lengths were 33.3 +/- 3.9
      mm, 33.6 +/- 3.6 mm, and 34.3 +/- 3.2 mm, respectively. A femoral tunnel length
      of less than 30 mm developed in 7 cases (24.1%) in the AM aspect and 4 cases
      (13.8%) in the PL aspect. The mean femoral tunnel divergent angle was 14.4
      degrees  +/- 4.1 degrees . A positive correlation was found between AM, not PL or
      central, femoral tunnel length and medial femoral condyle anteroposterior (AP)
      distance (P = .01, r = 0.46), lateral femoral condyle AP distance (P = .01, r =
      0.43), medial-to-lateral epicondylar distance (P = .03, r = 0.39), middle notch
      width (P = .009, r = 0.47), notch height (P = .001, r = 0.57), and notch area (P
      < .001, r = 0.58). CONCLUSIONS: After double-bundle ACL reconstruction with the
      transportal technique through the accessory anteromedial portal, the AM and PL
      femoral tunnels showed mean tunnel length greater than 30 mm and a divergent
      angle. However, a femoral tunnel length of less than 30 mm developed in some
      cases. AM femoral tunnel length was correlated with femoral condyle size (medial
      femoral condyle AP distance, lateral femoral condyle AP distance, and medial-to
      lateral epicondylar distance) and intercondylar notch size (notch width, notch
      height, and notch area). LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 22421567
TI  - Arthroscopic arthrolysis for recalcitrant frozen shoulder: a lateral approach.
AB  - PURPOSE: The purpose of this study was to evaluate a new all-arthroscopic
      technique in the management of recalcitrant globally stiff frozen shoulders. This
      adopts an initial extra-articular approach followed by intra-articular entry to
      perform a 360 degrees  capsular release. METHODS: Ten patients with global
      adhesive capsulitis were prospectively evaluated. All patients had not improved
      after undergoing a minimum of 6 months of physiotherapy, and 5 received intra
      articular injections of steroids. The mean age was 47 years (range, 33 to 56
      years). Patients were examined preoperatively and postoperatively for range of
      motion. A Constant score and visual analog scale score for pain were recorded. We
      described an all-arthroscopic technique by entering the subacromial space
      laterally and opening the rotator interval from the outside in, followed by a
      complete 360 degrees  capsular release and biceps tenotomy. RESULTS: The mean
      follow-up was 42 months (range, 18 to 90 months), and the mean Constant score
      improved from 21 to 72 (P < .01). Preoperative abduction improved from a mean of
      40 degrees  to 165 degrees , elevation improved from 55 degrees  to 175 degrees ,
      and external rotation improved from 6 degrees  to 58 degrees . The visual analog
      scale pain score improved from 7 to 1.6, and all patients reported an excellent
      outcome after surgery. There were no complications particularly regarding
      axillary nerve injury, fracture, or infection. CONCLUSIONS: This study shows a
      combined extra-articular and intra-articular approach that is controlled and
      anatomic and achieves excellent results that were maintained at the midterm. The
      technique permits anatomic debridement of the rotator interval, enabling
      excellent intra-articular access, a circumferential capsular release, and biceps
      tenotomy. There were no complications, and no manipulations were required, which
      pose a risk of creating soft-tissue lesions, fractures, or dislocations. We
      recommend this 360 degrees  capsular release technique for releasing globally
      stiff shoulders where the surgeon is experienced in arthroscopy.

PMID- 22421568
TI  - Patterns of BCR/ABL Gene Rearrangements in Chronic Myeloid Leukemia with Complex
      t(9;22) Using Fluorescence In Situ Hybridization (FISH).
AB  - Chronic myeloid leukemia (CML) is characterized by the reciprocal translocation
      t(9;22)(q34;q11.2) which fuses the ABL1 oncogene    on chromosome 9 with the BCR 
      gene on chromosome 22. It is the BCR/ABL protein that drives the neoplasm and the
      ABL/BCR is not    necessary for the disease. In the majority of CML cases, the 
      BCR/ABL fusion gene is cytogenetically recognizable as a small derivative   
      chromosome 22(der 22), which is known as the Philadelphia (Ph) chromosome.
      However, approximately 2-10% of patients with CML    involve cryptic or complex
      variant translocations with deletions on the der(9) and/or der(22) occuring in
      roughly 10-15% of CML  cases.    Fluorescence in situ hybridization (FISH)
      analysis can help identify deletions and complex or cryptic rearrangements.
      Various BCR/ABL    FISH probes are available, which include dual color single
      fusion, dual color extra signal (ES), dual color dual fusion and tri color dual  
      fusion probes. To test the utility of these probes, six patients diagnosed with
      CML carrying different complex variant Ph translocations    were studied by G
      banding and FISH analysis using the BCR/ABL ES, BCR/ABL dual color dual fusion,
      and BCR/ABL tricolor probes.    There are differences among the probes in their
      ability to detect variant rearrangements, with or without accompanying chromoso
      me 9    and/or 22 deletions, and low level disease.

PMID- 22421570
TI  - Change in atrial fibrillation status, comments to Val-FAAP registry.

PMID- 22421572
TI  - The many roles of IL-7 in B cell development; mediator of survival, proliferation
      and differentiation.
AB  - Interleukin-7 (IL-7) plays several important roles during B cell development
      including aiding in; the specification and commitment of cells to the B lineage,
      the proliferation and survival of B cell progenitors; and maturation during the
      pro-B to pre-B cell transition. Regulation and modulation of IL-7 receptor (IL
      7R) signaling is critical during B lymphopoiesis, because excessive or deficient
      IL-7R signaling leads to abnormal or inhibited B cell development. IL-7 works
      together with E2A, EBF, Pax-5 and other transcription factors to regulate B cell
      commitment, while also functions to regulate Ig rearrangement by modulating FoxO
      protein activation and Rag enhancer activity. Suppressor of cytokine signaling
      (SOCS) proteins are inhibitors of cytokine activation and, in B cells, function
      to fine tune IL-7R signaling; ensuring that appropriate IL-7 signals are
      transmitted to allow for efficient B cell commitment and development.

PMID- 22421571
TI  - Intrathymic IL-7: the where, when, and why of IL-7 signaling during T cell
      development.
AB  - The thymus is the birthplace of all T lineage cells. But the thymus is also a
      cradle as it provides the environment for further maturation and differentiation
      of immature thymocytes. While many factors contribute to make the thymus a unique
      place for T cell development, here we review the essential role of intrathymic
      interleukin-7 (IL-7). In the absence of IL-7 signaling, survival, proliferation
      and differentiation of immature thymocytes are all severely impaired.
      Consequently, IL-7 is critical to nurture and guide T precursor cells through the
      diverse steps of thymic maturation. Interestingly, even as IL-7 signaling is such
      a critical factor, IL-7 signaling must be also actively suppressed during
      specific stages of T cell differentiation. These contradictory observations are
      puzzling but can be satisfactorily explained when understanding the developmental
      context of IL-7 signaling. In this regard, here we will discuss the
      spatiotemporal expression of intrathymic IL-7 and address the stage-specific
      effects of IL-7 signaling in developing thymocytes. Specifically, we will review
      other facets of intrathymic IL-7 beyond its role as a pro-survival factor and so
      clarify and reaffirm the unique role of IL-7 as a prime factor in T cell
      development and differentiation.

PMID- 22421573
TI  - The key role of IL-7 in lymphopoiesis.
AB  - In mice, interleukin 7, although initially thought to be predominantly a cytokine
      acting on B cells, appears to have potent survival and growth activity during
      both B and T lymphopoiesis. Although acting on both lineages at the very immature
      stages, T cell differentiation becomes independent of IL-7 at the intermediate
      stages before regaining dependence on IL-7 for survival and proliferation at the
      mature T cell stage. In contrast, although essential for B lymphopoiesis, mature
      B cell survival is independent of IL-7. In this review, we focus on and discuss
      the similarities and differences between the role of IL-7 in these two processes.

PMID- 22421574
TI  - The influence of HIV on CD127 expression and its potential implications for IL-7
      therapy.
AB  - Interleukin-7 (IL-7) is critical for early T-cell development and plays an
      important role in T-cell homeostasis, differentiation and function. Signalling
      via the IL-7 receptor is dependent on the expression of its components, IL
      7Ralpha (CD127) and IL-2Rgamma (CD132) and is mediated in part by alterations in
      CD127 expression levels in different cell subsets. Naive and memory T-cells
      express high levels of CD127, while effector cells are CD127(lo) and retention of
      the receptor is thought to influence the development of memory cells. Reduced
      expression of CD127 has been associated with markers of disease severity in HIV
      infection and other chronic viral infections as well as in various cancers. In
      HIV infection, decreased CD127 expression on T-cells is correlated with reduced
      CD4(+) T-cell counts, increased viral replication and immune activation. The loss
      of IL-7 activity, due to decreased CD127 expression, may contribute to the
      observed loss of CD8(+) cytotoxic T lymphocyte (CTL) activity in HIV infection.
      The downregulation of CD127 expression in HIV infection may be due to host (e.g.
      IL-7, IL-4, immune activation) and/or viral (e.g. HIV-tat) factors and mechanisms
      of receptor regulation may differ by cell type. In addition, the expression of a
      soluble form of CD127 (sCD127) has been shown to be increased in HIV infection.
      This protein may affect IL-7 activity in vivo and therefore may have implications
      for IL-7-based therapies which are currently being tested in clinical trials.
      Understanding how CD127 is regulated during HIV infection will provide insight
      for the development of novel therapeutics to improve immune function and anti
      viral T-cell activity.

PMID- 22421576
TI  - Evaluation of patient-rated stiffness associated with fibromyalgia: a post-hoc
      analysis of 4 pooled, randomized clinical trials of duloxetine.
AB  - BACKGROUND: Patients with fibromyalgia (FM) rate stiffness as one of the most
      troublesome symptoms of the disorder. However, there are few published studies
      that have focused on better understanding the nature of stiffness in FM.
      OBJECTIVES: The primary objectives of these analyses were to characterize the
      distribution of stiffness severity in patients at baseline, evaluate changes in
      stiffness after 12 weeks of treatment with duloxetine, and determine which
      outcomes were correlated with stiffness. METHODS: These were post-hoc analyses of
      3-month data from 4 randomized, double-blind, placebo-controlled studies that
      assessed efficacy of duloxetine in adults with FM. Severity of stiffness was
      assessed by using the Fibromyalgia Impact Questionnaire (FIQ) on a scale from 0
      (no stiffness) to 10 (most severe stiffness). The association between changes in
      stiffness and other measures was evaluated by using Pearson's correlation
      coefficient. The FIQ total score and items, the Brief Pain Inventory (BPI
      modified short form), the Clinical Global Impression-Severity scale, the
      Multidimensional Fatigue Inventory, the 17-item Hamilton Depression Rating Scale,
      the Sheehan Disability Scale, the 36-item Short-Form Health Survey, and the
      EuroQoL Questionnaire-5 Dimensions were evaluated in the correlation analyses.
      Stepwise linear regression was used to identify the variables that were most
      highly predictive of the changes in FIQ stiffness. RESULTS: The analysis included
      1332 patients (mean age, 50.2 years; 94.7% female; and 87.8% white). The mean
      (SD) baseline FIQ stiffness score was 7.7 (2.0), and this score correlated with
      baseline BPI pain score and FIQ function. Duloxetine significantly improved the
      FIQ stiffness score compared with placebo (P < 0.001) and provided a moderate
      effect size (0.23 for the 60-mg dose and 0.38 for the 120-mg dose). Changes in
      stiffness were best correlated (range, 0.52-0.75; all, P < 0.001) with changes in
      BPI/FIQ pain and interference scores, FIQ nonrefreshing sleep, FIQ anxiety, 36
      item Short-Form Health Survey bodily pain, and Sheehan Disability Scale total
      score. Variables related to severity of pain, pain interfering with daily
      activities, and physical functioning were predictors of change in stiffness.
      CONCLUSIONS: Stiffness scores were high in this population with FM and best
      correlated at baseline with BPI pain score and FIQ function. Not unexpectedly,
      improvement in stiffness with duloxetine correlated with many of the other
      markers of FM severity, presumably a result of amelioration in FM comorbidities.

PMID- 22421577
TI  - Validation of a genotyping method for analysis of TPMT polymorphisms.
AB  - BACKGROUND: Thiopurine methyltransferase (TPMT) catalyzes the methylation of
      thiopurine drugs such as azathioprine and 6-mercaptopurine. Several mutations in
      the TPMT gene correlate with low enzyme activity and adverse effects such as
      myelotoxicity. Hence, genotyping TPMT makes it possible to identify patients at
      high risk for drug toxicity. OBJECTIVE: The aim of this study was to validate a
      TPMT genotyping method by comparing it with a conventional polymerase chain
      reaction (PCR) approach. METHODS: LightSNiP is a real-time PCR method for the
      detection of TPMT*2, *3B, and *3C without a sequencing step. We evaluated the
      frequencies of 3 TPMT alleles in 111 white adult patients by comparing genotyping
      by LightSNiP with conventional PCR (sequencing). RESULTS: No differences were
      observed between conventional genotyping with sequencing and LightSNiP for *2,
      *3B, and *3C, suggesting the validity of this method. CONCLUSIONS: Compared with
      the conventional PCR sequencing method, the data suggest that LightSNiP correctly
      detected the TPMT *2, *3B, and *3C in this select population.

PMID- 22421575
TI  - IL-7: the global builder of the innate lymphoid network and beyond, one niche at
      a time.
AB  - The development and homeostasis of adaptive and innate lymphocytes is dependent
      on the stromal cytokine IL-7. The initial priming of immune responses to
      pathogenic challenges is executed by innate lymphoid cells (ILCs) with programmed
      capacity to rapidly secrete effector cytokines. How ILCs are controlled by IL-7
      in distinct anatomical locale has evolved into a more complex problem as IL-7
      receptor is not only expressed on ILCs, but also on surrounding neighbors,
      including vascular endothelium and mesenchymal cells that compete for limiting IL
      7. For the generation of gammadelta T and B cells IL-7 is required for the
      production of antigen receptors, and it is likely that IL-7 performs critical
      function in facilitating ILC effector programming in addition to its regulatory
      actions on cell survival and proliferation. Most of our current understanding of
      the highly calibrated regulatory circuits of IL-7 function and IL-7 receptor
      signaling has derived from studies of adaptive, conventional lymphocytes. Here we
      highlight recent advances in mapping the gene circuits and cellular interactions
      that regulate temporospatial activities of IL-7 in diverse macro and micro niches
      that have direct relevance to deciphering the sphere of impact of IL-7 on ILC
      differentiation.

PMID- 22421578
TI  - External validation of aminoglycoside models used in web calculators and clinical
      decision support systems after laboratory conversion to serum creatinine isotope
      dilution mass spectrometry assay.
AB  - BACKGROUND: Models to predict gentamicin t(1/2) from serum creatinine (SCr)
      estimated creatinine clearance (CrCl) are currently being incorporated into smart
      device applications and clinical decision support modules without external
      validation. OBJECTIVE: The aim of this study was to determine whether such models
      remain viable after conversion to isotope dilution mass spectrometry (IDMS) SCr
      assay. METHODS: This study analyzed data from retrospective reviews of the
      medical records of nonobese adults receiving the aminoglycoside gentamicin and
      having >=2 evaluable serum gentamicin concentrations after laboratory IDMS SCr
      conversion, from January 2008 to August 2009, at a tertiary care hospital in
      Florida. A literature search found a number of cited aminoglycoside models. This
      group of models was classified as group 1. The World Wide Web was also searched
      for the term aminoglycoside dosing calculators, with 6 models found and referred
      to as group 2. Predictive performance measures were used to compare the model
      results with the t(1/2) calculated from gentamicin concentrations using the
      Nelder-Mead algorithm. RESULTS: The records of 39 patients met the inclusion
      criteria (23 men, 16 women; age range, 18-86 years; range of estimated CrCl, 55
      115 mL/min) and provided the "gold standard" aminoglycoside t(1/2). A gentamicin
      t(1/2) was predicted from several published models (group 1) and from other
      models used in online smart-device applications (group 2) and clinical decision
      modules. The median (interquartile range) root mean square errors were 0.48 (0.44
      to 0.65) and 0.48 (0.45 to 0.70) hours from group-1 and -2 models, respectively.
      The median mean relative prediction errors were 9% (-14% to +13%) and 11% (+1% to
      +21%) from groups 1 and 2. The median mean absolute prediction errors were 21%
      (19% to 28%) and 21% (20% to 30%) from groups 1 and 2. Adjusting SCr by +20%
      improved the predictive ability in 3 of 12 cited models and in 5 of 6 models used
      in applications. CONCLUSIONS: Models to predict gentamicin t(1/2) should be
      externally validated at one's institution before use. The findings from the
      present study provide a framework for conducting external validation.

PMID- 22421579
TI  - Prediction of survival, second fracture, and functional recovery following the
      first hip fracture surgery in elderly patients.
AB  - This study was designed to investigate predictable factors of mortality, second
      fracture, and functional recovery within 24 months of hip fracture surgery in
      elderly patients. In addition, the authors sought to identify differences in
      survival and functional outcomes according to fracture type. Four hundred and
      fifteen patients with acute, first-time and lower-energy trauma hip fractures
      were enrolled into this prospective cohort study and followed for a minimum of 24
      months. The potential risk factors of mortality and functional outcomes
      considered were; (1) age, gender, body mass index, previous fracture history,
      preoperative ambulatory ability and residency type; (2) 8 comorbidity items,
      cognitive impairment, smoking, and American Society of Anesthesiologists'
      classification; and (3) delay prior to surgery, fracture type, operation time,
      operation method, and postoperative fall history. Multivariate logistic
      regression and Cox regression models were used for analysis. One-year and 2-year
      mortality rates after hip fracture surgery were 14.7% and 24.3%, respectively.
      The 2-year second fracture rate was 9.2% and the 2-year functional recovery rate
      was 38.6%. Advanced age, cancer, a prior fracture history, and a solitary life
      were found to be significantly associated with the risk of increased 2-year
      mortality. A fall within 1 year of surgery and a solitary life were found to be
      closely associated with the risk of a second fracture, and malignancy and
      cognitive impairment with a poor functional outcome. Operation time and the 2
      year second fracture rate differed significantly between the two fracture groups.
      An understanding of the incidences and risk factors of mortality and
      postoperative outcomes following hip fracture surgery in elderly patients
      provides a valuable basis to improve in health care of geriatric population.

PMID- 22421581
TI  - An official American Thoracic Society workshop report: Climate change and human
      health.
AB  - This document presents the proceedings from the American Thoracic Society Climate
      Change and Respiratory Health Workshop that was held on May 15, 2010, in New
      Orleans, Louisiana. The purpose of the one-day meeting was to address the threat
      to global respiratory health posed by climate change. Domestic and international
      experts as well as representatives of international respiratory societies and key
      U.S. federal agencies convened to identify necessary research questions
      concerning climate change and respiratory health and appropriate mechanisms and
      infrastructure needs for answering these questions. After much discussion, a
      breakout group compiled 27 recommendations for physicians, researchers, and
      policy makers. These recommendations are listed under main issues that the
      workshop participants deemed of key importance to respiratory health. Issues
      include the following: (1) the health impacts of climate change, with specific
      focus on the effect of heat waves, air pollution, and natural cycles; (2)
      mitigation and adaptation measures to be taken, with special emphasis on
      recommendations for the clinical and research community; (3) recognition of
      challenges specific to low-resource countries when coping with respiratory health
      and climate change; and (4) priority research infrastructure needs, with special
      discussion of international needs for cooperating with present and future
      environmental monitoring and alert systems.

PMID- 22421583
TI  - Notice of duplicate publication.

PMID- 22421582
TI  - An official American Thoracic Society workshop report: the Integrated Care of The
      COPD Patient.
AB  - The optimal care of the patient with chronic obstructive pulmonary disease (COPD)
      requires an individualized, patient-centered approach that recognizes and treats
      all aspects of the disease, addresses the systemic effects and comorbidities, and
      integrates medical care among healthcare professionals and across healthcare
      sectors. In many ways the integration of medical care for COPD is still in its
      infancy, and its implementation will undoubtedly represent a paradigm shift in
      our thinking. This article summarizes the proceedings of a workshop, The
      Integrated Care of the COPD Patient, which was funded by the American Thoracic
      Society. This workshop included participants who were chosen because of their
      expertise in the area as well as their firsthand experience with disease
      management models. Our summary describes the concepts of integrated care and
      chronic disease management, details specific components of disease management as
      they may apply to the patient with COPD, and provides several innovative examples
      of COPD disease management programs originating from different healthcare
      systems. It became clear from the discussions and review of the literature that
      more high-quality research in this area is vital. It is our hope that the
      information presented here provides a "call to arms" in this regard.

PMID- 22421584
TI  - The genotoxic, hepatotoxic, nephrotoxic, haematotoxic and histopathological
      effects in rats after aluminium chronic intoxication.
AB  - Aluminium (Al) is used in water purification and is also present in several
      manufactured foods and medicines. Al is known to induce a broad range of
      physiological, biochemical and behavioural dysfunctions in laboratory animals and
      humans. This investigation was carried out to investigate the effects of
      subchronic exposure to Al (as AlCl3) in rats. Sprague-Dawley rats were randomly
      separated into two groups. Group 1 rats treated with sodium chloride served as
      the control, group 2 rats were treated with Al (as AlCl3, 5 mg/kg body weight)
      intraperitonally for 10 weeks. Animals were killed and blood samples were
      analyzed for blood serum alkaline phosphatase (ALP), aspartate aminotransferase
      (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) enzyme
      activities and creatinine, urea (U) and uric acid (UA) levels for evaluating
      hepatotoxicity and nephrotoxicity. Blood parameters including red blood cells
      (RBCs), haemoglobin (Hb) concentration, haematocrit (Ht), platelets (PLTs) and
      white blood cells (WBCs) were compared between control and experimental group to
      assess haematoxicity. In order to determine the genotoxicity, the number of
      micronucleated hepatocytes (MNHEPs) was counted in isolated hepatocytes. In
      addition, histological alterations in liver and kidney samples were investigated.
      After exposure with Al, the enzymatic activities of ALP, AST, ALT and LDH, and
      the levels of U and UA significantly increased. RBC, WBC, PLT, Hb and Ht revealed
      significant decreases in experimental group compared to the control. AlCl3 caused
      a significant increase in MNHEPs. Furthermore, severe pathological damages were
      established in both liver and kidney samples. Subchronic exposure to low doses of
      Al can produce serious dysfunctions in rat blood, liver and kidney, and exposure
      to this metal can result in greater damages.

PMID- 22421585
TI  - Protective value of prophylactic antibiotic treatment of tick bite for Lyme
      disease prevention: an animal model.
AB  - Clinical studies have demonstrated that prophylactic antibiotic treatment of tick
      bites by Ixodes scapularis in Lyme disease hyperendemic regions in the
      northeastern United States can be effective in preventing infection with Borrelia
      burgdorferi sensu stricto, the Lyme disease spirochete. A large clinical trial in
      Westchester County, NY (USA), demonstrated that treatment of tick bite with 200mg
      of oral doxycycline was 87% effective in preventing Lyme disease in tick-bite
      victims (Nadelman, R.B., Nowakowski, J., Fish, D., Falco, R.C., Freeman, K.,
      McKenna, D., Welch, P., Marcus, R., Aguero-Rosenfeld, M.E., Dennis, D.T.,
      Wormser, G.P., 2001. Prophylaxis with single-dose doxycycline for the prevention
      of Lyme disease after an Ixodes scapularis tick bite. N. Engl. J. Med. 345, 79
      84.). Although this excellent clinical trial provided much needed information,
      the authors enrolled subjects if the tick bite occurred within 3 days of their
      clinical visit, but did not analyze the data based on the exact time between tick
      removal and delivery of prophylaxis. An animal model allows for controlled
      experiments designed to determine the point in time after tick bite when delivery
      of oral antibiotics would be too late to prevent infection with B. burgdorferi.
      Accordingly, we developed a tick-bite prophylaxis model in mice that gave a level
      of prophylactic protection similar to what had been observed in clinical trials
      and then varied the time post tick bite of antibiotic delivery. We found that two
      treatments of doxycycline delivered by oral gavage to mice on the day of removal
      of a single potentially infectious nymphal I. scapularis protected 74% of test
      mice compared to controls. When treatment was delayed until 24 h after tick
      removal, only 47% of mice were protected; prophylactic treatment was totally
      ineffective when delivered >=2 days after tick removal. Although the dynamics of
      antibiotic treatment in mice may differ from humans, and translation of animal
      studies to patient management must be approached with caution, we believe our
      results emphasize the point that antibiotic prophylactic treatment of tick bite
      to prevent Lyme disease is more likely to be efficacious if delivered promptly
      after potentially infectious ticks are removed from patients. There is only a
      very narrow window for prophylactic treatment to be effective post tick removal.

PMID- 22421586
TI  - Restless legs syndrome responsive to rasagiline treatment:  a case report.
AB  - We describe a patient with idiopathic restless legs syndrome (iRLS) who was
      responsive to rasagiline treatment. A 70-year-old woman presented with an 8-year
      history of iRLS symptoms and a 1-year history of resting tremor. The patient met
      the UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria (UK
      Parkinson Disease [PD] Brain Bank criteria) for the diagnosis of idiopathic PD
      and the criteria of the International Restless Legs Syndrome Study Group for the
      diagnosis of iRLS. One milligram of rasagiline once daily was started with the
      diagnosis of early PD as monotherapy. At week 8, the patient was almost iRLS
      symptoms free. Rasagiline has also been shown to mildly improve PD symptoms.
      Rasagiline was well tolerated during the follow-up. We suggest that rasagiline
      could represent a useful therapeutic option in the treatment of iRLS.

PMID- 22421587
TI  - Rituximab and multiple sclerosis.
AB  - B lymphocytes seem to have a fundamental role in multiple sclerosis, acting as
      sensors, coordinators, and regulators of the immune response. Furthermore, they
      are important in activating T cells and they can mediate tissue injury through
      diverse mechanisms. Such findings have important therapeutic implications in
      autoimmune central nervous system diseases in a fashion similar to other
      autoimmune processes. The best known monoclonal antibody targeting B cells that
      has been used as a novel therapy for various autoimmune conditions, as well as
      multiple sclerosis, is rituximab. This review summarizes the available data on
      the role of B cell in multiple sclerosis and further reports on current knowledge
      on the B-cell-depleting monoclonal antibody rituximab, its mechanism of action,
      and its efficacy on multiple sclerosis. Data presented were categorized in 3
      groups based on the nature of data presented (radiological, clinical, and
      immunological data). Both case-control studies and case reports were included,
      while table classification was in chronological order.

PMID- 22421588
TI  - An enzymatic immunoassay microfluidics integrated with membrane valves for
      microsphere retention and reagent mixing.
AB  - The present study presents a new microfluidic device integrated with pneumatic
      microvalves and a membrane mixer for enzyme-based immunoassay of acute myocardial
      infarction (AMI) biomarkers, namely, myoglobin, and heart-type fatty acid binding
      protein (H-FABP). Superparamagnetic microspheres with carboxyl groups on their
      surfaces were used as antibody solid carriers. A membrane mixer consisting of
      four psi-type membrane valves was assembled under the reaction chamber for on
      chip performing microsphere trapping and reagent mixing. The entire immunoassay
      process, including microsphere capture, reagent input, mixing, and subsequent
      reaction, was accomplished on the device either automatically or manually. The
      post-reaction substrate resultant was analyzed using a microplate reader. The
      results show that the average absorbance value is correlated with the
      concentration of cardiac markers, in agreement with the results obtained using a
      conventional microsphere-based immunoassay; this indicated that the proposed on
      chip immunoassay protocol could be used to detect both myoglobin and H-FABP. The
      minimum detectable concentration is 5 ng/mL for myoglobin and 1 ng/mL for H-FABP.

PMID- 22421589
TI  - 20-year experience of prolonged extracorporeal membrane oxygenation in critically
      ill children with cardiac or pulmonary failure.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for
      life-threatening respiratory or circulatory failure. Although outcomes are
      favorable with short-term ECMO therapy, data on the outcomes of prolonged ECMO
      therapy in children are very limited. This study aimed to study morbidity and
      mortality associated with prolonged ECMO therapy (>=28 days) in children with
      refractory cardiac or pulmonary failure. METHODS: We conducted a retrospective
      review of all children<=18 years supported with ECMO for >=28 days between
      January 1991 and September 2011 at the Arkansas Children's Hospital. The data
      collected in our study included patient demographic information; diagnosis;
      indication for ECMO; ECMO support details; medical and surgical history;
      laboratory, microbiologic, and radiographic data; information on organ
      dysfunction; complications; and patient outcomes. The outcome variables evaluated
      in this report included survival to ECMO decannulation, survival to hospital
      discharge, and current survival with emphasis on neurologic, renal, pulmonary,
      and other end organ function. RESULTS: During the study period, 984 events in 951
      patients were supported with ECMO with a 30-day survival of 666 events (68%).
      Only 22 ECMO runs were >=28 days and were eligible for inclusion in this report.
      The longest ECMO run in our series was 1,206 hours (50 days). The average length
      of ECMO run in this cohort was 855+/-133 hours, with a mean intensive care unit
      length of stay of 56+/-27 days. Ten patients (45%) were successfully decannulated
      from ECMO. Six patients (27%) were alive 30 days after decannulation, and only 4
      patients (19%) survived to hospital discharge. Of the 4 survivors, only 3
      patients (14%) are living to date. Of the 3 living children, 2 have significant
      neurologic issues with brain atrophy and developmental delay, and 1 is awaiting
      renal transplant; all 3 survivors have chronic lung disease. CONCLUSIONS: This
      case series highlights that the prolonged use of ECMO in children with refractory
      cardiac failure, respiratory failure, or both is associated with low survival.
      Furthermore, it suggests that the survivors of prolonged ECMO runs have
      significant long-term sequelae.

PMID- 22421590
TI  - Thymic carcinoma: outcomes after surgical resection.
AB  - BACKGROUND: Thymic carcinoma is a rare malignancy with little information
      regarding outcomes after therapy with curative intent. We undertook a
      retrospective analysis of all patients who underwent resection of thymic
      carcinoma at 2 hospitals. METHODS: From 1990 to 2011, 16 patients (9 men, 7
      women) underwent surgical resection of thymic carcinoma at a mean age of 52
      years. Patient demographics, extent of surgical resection, and outcomes were
      compiled. RESULTS: The distribution of Masaoka stages at presentation was I in 3
      (19%), II in 4 (25%), III in 8 (50%), and IV in 1 (6%). Neoadjuvant chemotherapy
      was administered to 6 patients (38%) whose tumors were deemed to be more locally
      invasive. Surgical resection included en bloc extrapleural pneumonectomy in 1,
      lobectomy in 2, and superior vena cava resection and reconstruction in 4. There
      were no perioperative deaths. Complete resection was achieved in 14 (88%), and of
      these patients, only 1 experienced local recurrence. At last follow-up, 10
      patients were alive and well, 1 patient was alive with disease, and 5 patients
      had died. Mean survival was 4.2 years. CONCLUSIONS: Although considered to have
      greater malignant potential, long-term survival can be achieved in patients with
      thymic carcinoma who are amenable to surgical therapy. With increased use of
      computed tomography imaging, patients with early-stage disease are being
      identified more frequently, and complete surgical resection appears to have
      favorable cure rates in these patients. Select patients with locally advanced
      disease can experience long-term survival with a multimodality approach.

PMID- 22421591
TI  - Impact of timing and surgical approach on outcomes after mitral valve
      regurgitation operations.
AB  - BACKGROUND: This study investigated whether the timing of mitral valve (MV)
      repair or surgical approach affects outcomes in patients with MV regurgitation.
      METHODS: Between 1992 and 2009, 2,255 patients underwent MV operations, including
      1,305 with isolated MV regurgitation operations (1,054 repairs, 251
      replacements). Surgical approaches were sternotomy in 377, video-assisted right
      minithoracotomy in 481, or robot-assisted in 447. Mean follow-up was 6.4+/-4.5
      years (maximum, 19 years). RESULTS: Sternotomy MV repairs decreased during the
      study while minimally invasive MV repairs increased. Robotic MV repair patients
      were younger, with fewer women, had better left ventricular ejection fractions,
      and were more likely to have myxomatous degeneration (all p<0.001). The robotic
      approach led to a higher MV repair rate and increased use of leaflet/chordal
      procedures but had longer cardiopulmonary bypass and aortic cross-clamp times
      (all p<0.001). The 30-day mortality for isolated MV repair was similar for all
      approaches (p=0.409). Fewer neurological events were observed in the videoscopic
      and robotic groups (p=0.013). Adjusted survival was similar for all approaches
      (p=0.357). Survival in patients in New York Heart Association class I to II with
      myxomatous degeneration or annular dilatation was similar to a matched population
      but was worse for patients in class III to IV or undergoing MV replacement.
      CONCLUSIONS: MV repair in patients with severe MV regurgitation should be
      performed before New York Heart Association class III to IV symptoms develop.
      Minimally invasive MV repair techniques render similar outcomes as the sternotomy
      approach.

PMID- 22421592
TI  - Influence of cigarette smoking on survival and tumor invasiveness in clinical
      stage IA lung adenocarcinoma.
AB  - BACKGROUND: The objective of this study was to investigate the association
      between cigarette smoking, cancer survival, and pathological features of clinical
      stage IA lung adenocarcinoma. METHODS: Between August 1992 and December 2007,
      1,070 consecutive patients with clinical stage IA lung adenocarcinoma underwent
      complete resection with systematic lymph node dissection. Univariate analysis by
      log-rank tests was performed to determine unfavorable prognostic factors, and the
      Cox proportional hazards regression model was used to identify the potential
      independent predictors. RESULTS: The overall 5-year survival rate of patients
      with greater than 20 pack-years (PY>20) was 71%, significantly lower than
      patients with 20 or less pack-years (PY<=20; 86%; p<0.001). Postoperative
      pathological prognostic factors, including moderate or poor histologic
      differentiation, lymphatic permeation, intratumoral vascular invasion, visceral
      pleural invasion, and lymph node metastasis, were detected more often in patients
      with greater than 20 PY. Sixty-five percent of the patients in this study had
      pathological stage IA tumors, and their overall 5-year survival rates with 20 or
      less PY and greater than 20 PY were 97% and 86%, respectively (p<0.001).
      CONCLUSIONS: In patients with clinical stage IA adenocarcinoma, a history of
      heavy smoking was associated with poor outcomes and was a statistically
      significant predictor of histologic tumor invasion.

PMID- 22421593
TI  - Postoperative assessment of laryngopharyngeal dysfunction in neonates after
      Norwood operation.
AB  - BACKGROUND: The purpose of this study was to evaluate the incidence of vocal cord
      (VC) and swallowing dysfunction in infants after the Norwood operation and to
      examine the relationship between laryngopharyngeal dysfunction and postoperative
      outcomes. METHODS: We conducted a retrospective review of 63 infants who
      underwent routine postoperative fiberoptic endoscopic evaluation of swallowing
      function and vocal cords after a Norwood operation at our institution during a
      recent 6-year period (2003-2009). RESULTS: The overall incidence of VC
      dysfunction after the Norwood operation was 58.7%. After a modification of the
      aortic arch dissection technique in 2007, the incidence of VC dysfunction
      decreased significantly from 79.5% in 2003 through 2006 to 25% in 2007 through
      2009 (p<0.001). The incidence of swallowing dysfunction also decreased from 23.1%
      in 2003 through 2006 to 4.2% in 2007 through 2009 (p=0.07). Swallowing
      dysfunction was more common in patients with VC dysfunction (21.6%) as compared
      with patients without VC dysfunction (7.7%; p=0.18). Patients with VC dysfunction
      were more often discharged home on tube-only feeding regimens compared with
      infants without VC dysfunction (46% versus 26.9%). In infants with both VC and
      swallowing dysfunction, 75% were discharged exclusively to have tube feeding.
      Median hospital length of stay tended to be longer in infants with swallowing
      dysfunction (31 days) than in infants without swallowing dysfunction (23 days;
      p=0.16). CONCLUSIONS: Vocal cord and swallowing dysfunction are common in infants
      after the Norwood operation and may increase the need for tube feeding regimens.
      Modification of surgical techniques for dissection and mobilization of the aorta
      can significantly reduce the incidence of these adverse outcomes.

PMID- 22421594
TI  - Perlecan modulates VEGF signaling and is essential for vascularization in
      endochondral bone formation.
AB  - Perlecan (Hspg2) is a heparan sulfate proteoglycan expressed in basement
      membranes and cartilage. Perlecan deficiency (Hspg2(-/-)) in mice and humans
      causes lethal chondrodysplasia, which indicates that perlecan is essential for
      cartilage development. However, the function of perlecan in endochondral
      ossification is not clear. Here, we report the critical role of perlecan in VEGF
      signaling and angiogenesis in growth plate formation. The Hspg2(-/-) growth plate
      was significantly wider but shorter due to severely impaired endochondral bone
      formation. Hypertrophic chondrocytes were differentiated in Hspg2(-/-) growth
      plates; however, removal of the hypertrophic matrix and calcified cartilage was
      inhibited. Although the expression of MMP-13, CTGF, and VEGFA was significantly
      upregulated in Hspg2(-/-) growth plates, vascular invasion into the hypertrophic
      zone was impaired, which resulted in an almost complete lack of bone marrow and
      trabecular bone. We demonstrated that cartilage perlecan promoted activation of
      VEGF/VEGFR by binding to the VEGFR of endothelial cells. Expression of the
      perlecan transgene specific to the cartilage of Hspg2(-/-) mice rescued their
      perinatal lethality and growth plate abnormalities, and vascularization into the
      growth plate was restored, indicating that perlecan in the growth plate, not in
      endothelial cells, is critical in this process. These results suggest that
      perlecan in cartilage is required for activating VEGFR signaling of endothelial
      cells for vascular invasion and for osteoblast migration into the growth plate.
      Thus, perlecan in cartilage plays a critical role in endochondral bone formation
      by promoting angiogenesis essential for cartilage matrix remodeling and
      subsequent endochondral bone formation.

PMID- 22421597
TI  - A global health workforce for diabetes IDF Centres of Education working to
      strengthen capacity.

PMID- 22421595
TI  - Connective tissue mineralization in Abcc6-/- mice, a model for pseudoxanthoma
      elasticum.
AB  - Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder characterized
      by ectopic mineralization. However, the structure of the mineral deposits, their
      interactions with the connective tissue matrix, and the details of the
      progressive maturation of the mineral crystals are currently unknown. In this
      study, we examined the mineralization processes in Abcc6(-/-) mice, a model
      system for PXE, by energy dispersive X-ray and Fourier transform infrared imaging
      spectroscopy (FT-IRIS). The results indicated that the principal components of
      the mineral deposits were calcium and phosphate which co-localized within the
      histologically demonstrable lesions determined by topographic mapping. The Ca/P
      ratio increased in samples with progressive mineralization reaching the value
      comparable to that in endochondral bone. A progressive increase in mineralization
      was also reflected by increased mineral-to-matrix ratio determined by FT-IRIS.
      Determination of the mineral phases by FT-IRIS suggested progressive maturation
      of the mineral deposits from amorphous calcium phosphate to hydroxyapatite. These
      results provide critical information of the mechanisms of mineralization in PXE,
      with potential pharmacologic implications.

PMID- 22421598
TI  - Potential for use of 1,5-anhydroglucitol when initiating insulin therapy in
      people with type 2 diabetes and suboptimal control with oral antidiabetic drugs.
AB  - Endpoint HbA(1c) <7.0% was achieved by 80 (73.4%) lispro mix 25 (LM25)-treated
      patients and 67 (60.9%) glargine-treated patients (p=0.027) with baseline 1,5
      anhydroglucitol (1,5AG) below median and 75 (70.8%) LM25-treated patients and 72
      (63.7%) glargine-treated patients (p=0.238) with 1,5AG>=median, suggesting, 1,5AG
      may offer therapeutic insight when starting insulin therapy.

PMID- 22421599
TI  - [A history of nicotine: two hundred years later].

PMID- 22421596
TI  - Cannabinoid receptors: nomenclature and pharmacological principles.
AB  - The CB1 and CB2 cannabinoid receptors are members of the G protein-coupled
      receptor (GPCR) family that are pharmacologically well defined. However, the
      discovery of additional sites of action for endocannabinoids as well as synthetic
      cannabinoid compounds suggests the existence of additional cannabinoid receptors.
      Here we review this evidence, as well as the current nomenclature for classifying
      a target as a cannabinoid receptor. Basic pharmacological definitions, principles
      and experimental conditions are discussed in order to place in context the
      mechanisms underlying cannabinoid receptor activation. Constitutive (agonist
      independent) activity is observed with the overexpression of many GPCRs,
      including cannabinoid receptors. Allosteric modulators can alter the
      pharmacological responses of cannabinoid receptors. The complex molecular
      architecture of each of the cannabinoid receptors allows for a single receptor to
      recognize multiple classes of compounds and produce an array of distinct
      downstream effects. Natural polymorphisms and alternative splice variants may
      also contribute to their pharmacological diversity. As our knowledge of the
      distinct differences grows, we may be able to target select receptor
      conformations and their corresponding pharmacological responses. Importantly, the
      basic biology of the endocannabinoid system will continue to be revealed by
      ongoing investigations.

PMID- 22421600
TI  - [Altitude and the cardiovascular system].
AB  - A stay at high altitude exposes an individual to various environmental changes
      (cold, exercise, isolation) but the most stressful for the body is hypoxia.
      However, the cardiovascular system yields some efficient mechanisms of
      acclimatization to oxygen lack. Hypoxia activates the adrenergic system and
      induces a tachycardia that decreases during a prolonged stay at altitude. The
      desensitization of the adrenergic system leads to a decrease in maximal heart
      rate and a protection of the myocardium against an energy disequilibrium that
      could be potentially harmful for the heart. Hypoxia induces a peripheral
      vasodilation and a pulmonary vasoconstriction, leading to few changes in systemic
      blood pressure and an increase in pulmonary blood pressure (PHT) that can
      contribute to a high altitude pulmonary edema. Advice to a cardiac patient who
      plans to go to high altitude should take into account that all diseases
      aggravated by increased adrenergic activity or associated with a PHT or a
      hypoxemia (right-to-left shunt) will be aggravated at high altitude. As altitude
      increases, a patient with a coronary disease will present an ischemic threshold
      for a lower power output during an EKG exercise test. The only test allowing
      predicting the tolerance to high altitude is the hypoxia exercise test realized
      at 30% of maxVO(2)and at an equivalent altitude of 4,800m.

PMID- 22421601
TI  - [Posterior reversible encephalopathy syndrome in an adult patient with sickle
      cell anemia].

PMID- 22421602
TI  - Trichinellosis in developing countries: is it neglected?
AB  - Trichinellosis is a foodborne zoonosis caused by the parasitic nematode
      Trichinella, which is characterized by an extremely wide host range and
      geographical distribution. The aim of the present review is to provide
      epidemiological information on animal and human trichinellosis occurring in
      developing countries in the different continents, where cooking habits along with
      poverty and poor sanitary conditions and lack of veterinary controls may
      facilitate the occurrence of human trichinellosis outbreaks. Countries have been
      considered according to the six regions designated by the World Health
      Organization (WHO): 1) WHO African Region, 2) WHO Region of the Americas, 3) WHO
      South-East Asia Region, 4) WHO European Region, 5) WHO Eastern Mediterranean
      Region, and 6) WHO Western Pacific Region. For the purposes of this article,
      developing countries are defined as those not industrialised according to the
      World Economic Outlook Report of the International Monetary Fund
      (http://www.imf.org); however, with regard to the European Region of WHO, only
      those countries that are not member states of the European Union will be
      considered.

PMID- 22421603
TI  - Methicillin-resistant Staphylococcus aureus metrics for patients in Saudi Arabia.
AB  - INTRODUCTION: The World Health Organization recommends essential measures to
      "combat drug resistance", including instituting surveillance "everywhere".
      Standardized metrics are crucial for reliable surveillance. Studies publish
      metrics with varying definitions for multi-drug resistant organisms (MDRO). The
      Society for Healthcare Epidemiology of America (SHEA) and the Healthcare
      Infection Control Practices Advisory Committee (HICPAC) proposed standardized
      metrics for MDRO for consistent reporting, identifying high-risk groups, and
      evaluating interventions. METHODOLOGY: We retrieved 73 studies through PubMed
      using the search terms "methicillin-resistant Staphylococcus aureus", "MRSA", and
      "Saudi Arabia". We selected 20 studies that reported MRSA incidence or prevalence
      in patients and/or percentage among Staphylococcus aureus isolates and evaluated
      these metrics against the closest matching SHEA/HICPAC metrics. RESULTS: We
      outlined issues applicable to MRSA metrics such as comparison of risk-unadjusted
      metrics; their pooling for different hospitals; not accounting for post-discharge
      infections; non-specification of AST-based, and healthcare and community
      associated infections' related, standardized metrics by SHEA/HICPAC; and
      appropriate temporal criteria for nosocomial infections. We elaborated salient
      features of reviewed metrics versus their SHEA/HICPAC complements. Terminology
      and definitions of reviewed metrics differed from SHEA/HICPAC counterparts. Some
      did not satisfy the epidemiological or statistical criteria for their reported
      category; e.g. prevalence indicators were classified as incidence and vice versa.
      CONCLUSIONS: SHEA/HICPAC metrics would be useful for future studies. Our results
      show an imminent need for an international consensus on fundamental MDRO
      surveillance metrics; illustrate surveillance scenarios requiring standardized
      metrics; identify some indicators from Saudi studies supplementing SHEA/HICPAC
      metrics; and underscore SHEA/HICPAC's advice for avoiding comparison of risk
      unadjusted metrics between hospitals.

PMID- 22421604
TI  - Epidemic cholera in Kakuma Refugee Camp, Kenya, 2009: the importance of
      sanitation and soap.
AB  - INTRODUCTION: Cholera remains a major public health problem that causes
      substantial morbidity and mortality in displaced populations due to inadequate or
      unprotected water supplies, poor sanitation and hygiene, overcrowding, and
      limited resources. A cholera outbreak with 224 cases and four deaths occurred in
      Kakuma Refugee Camp in Kenya from September to December 2009. METHODOLOGY: We
      conducted a case-control study to characterize the epidemiology of the outbreak.
      Cases were identified by reviewing the hospital registry for patients meeting the
      World Health Organization (WHO) case definition for cholera. For each case a
      matched control was selected. A questionnaire focusing on potential risk factors
      was administered to cases and controls. RESULTS: From 18 September to 15 December
      2009, a total of 224 cases were identified and were hospitalised at Kakuma IRC
      hospital.  Three refugees and one Kenyan national died of cholera. V. cholerae
      O1, serotype Inaba was isolated in 44 (42%) out of 104 stool specimens collected.
      A total of 93 cases and 93 matched controls were enrolled in the study. In a
      multivariate model, washing hands with soap was protective against cholera
      (adjusted odds ratio [AOR] =0.25[0.09-0.71]; p < 0.01), while presence of dirty
      water storage containers was a risk factor (AOR=4.39[1.12-17.14]; p=0.03).
      CONCLUSION: Provision of soap, along with education on hand hygiene and cleaning
      water storage containers, may be an affordable intervention to prevent cholera.

PMID- 22421606
TI  - Presence of Helicobacter pylori in drinking water of Karachi, Pakistan.
AB  - BACKGROUND: Prevalence of Helicobacter pylori (H. pylori) infection is an
      increasing problem in developing countries. Several environmental factors such as
      overcrowding, poverty, contaminated drinking water and food are considered to
      contribute toward transmission of infection; however, little is known about their
      definitive roles. The aim of this study is to investigate the presence of H.
      pylori in drinking water samples of Karachi, Pakistan. METHODOLOGY: Samples of
      drinking water were collected from 18 different towns located in the metropolitan
      area of Karachi. Samples were concentrated by membrane filtration method and
      subjected to PCR for the detection of H. pylori. RESULTS: Two out of 50 (4%)
      samples collected from two different densely populated town areas were found to
      be positive for H. pylori. CONCLUSION: The study provides evidence for the
      presence of H. pylori in municipal drinking water of Karachi.

PMID- 22421605
TI  - Prevalence of virulence determinants in Staphylococcus epidermidis from ICU
      patients in Kampala, Uganda.
AB  - INTRODUCTION: Staphylococcus epidermidis is often considered a non-pathogenic
      organism but it causes nosocomial infections. To distinguish invasive strains,
      comparative studies of patient and community isolates may offer some clues. We
      investigated the distribution of virulence determinants in patient isolates from
      Uganda. METHODOLOGY: S. epidermidis isolates were identified with the Staph API
      ID 32 kit. Antimicrobial susceptibility, biofilm formation and hemolysis were
      detected with standard procedures. Genes associated with virulence (aap, atlE,
      bhp, hla, hld, ica, IS256, sdrE, sea, tsst) and antimicrobial resistance (aac(6')
      Ie-aph(2'')-Ia, aph(3')-IIIa, ant(4')-Ia, blaZ, mecA, vanA/vanB1) were detected
      by PCR. RESULTS: S. epidermidis grew in 30 (30/50, 60%) ICU samples and 20
      (20/60, 33%) community samples (one isolate per sample per patient/person). All
      ICU isolates (30/30, 100%) were IS256 and hld positive, 22 (22/30, 73%) were
      biofilm/ica positive, 21 (21/30, 70%) were hemolytic on blood agar, nine (9/30,
      30%) contained atlE gene, six (6/30, 20%) hla gene, five (5/30, 17%) aap gene,
      and three (3/30, 10%) bhp gene. A gene encoding an aminoglycoside-modifying
      enzyme, aph(3')-IIIa, was highly prevalent (28/30, 93%), while blaZ (2/30, 7%),
      mecA (3/30, 10%), vanA (3/30, 10%) and vanB1 (3/30, 10%) were less prevalent. Of
      the community isolates, one (1/20, 5%) was ica positive, two (2/20, 10%) formed
      biofilms, and three (3/20, 15%) possessed the atlE gene. bhp, aap, IS256, hld and
      antimicrobial resistance genes were not detected in community isolates.
      CONCLUSIONS: S. epidermidis from ICU patients in Mulago Hospital is potentially
      virulent and could be a reservoir for antimicrobial resistant genes.

PMID- 22421607
TI  - Rats born to Brucella abortus infected mothers become latent carriers of
      Brucella.
AB  - INTRODUCTION: Rats are known to be infected with Brucella. Vertical transmission
      of brucellosis was recorded in rats. The study was performed to judge whether
      rats born from Brucella abortus infected mothers can act as latent carriers of
      Brucella infection. METHODOLOGY: Female Sprague Dawley (SD) rats were
      experimentally infected with B. abortus biotype 1 and subsequently bred 10 days
      post infection (PI). Serum samples of rats (n = 48) born from infected dams were
      tested using the Rose Bengal plate test (RBPT), tube agglutination test (TAT),
      and enzyme-linked immunosorbent assay (ELISA) at one, two and three months of
      age. Tissue samples were plated onto Brucella agar and blood agar media and
      incubated at 37  degrees C with 5% CO2 for five to seven days for isolation of
      bacteria. RESULTS: B. abortus was isolated from 18 out of 48 rats born to
      infected dams, and the isolates were confirmed as B. abortus by AMOS (B. abortus,
      melitensis, ovis and suis) PCR assay with the production of a 498 bp PCR
      amplicon. Serum samples of rats (n = 48) born from infected dams were tested
      negative using the RBPT, TAT and ELISA at all time points. CONCLUSION: We
      conclude from the study that rats born to infected dams may become latent
      carriers of Brucella infection potentially providing a reservoir for future
      transmission.

PMID- 22421608
TI  - Health-care providers' preparedness for H1N1/09 influenza prevention and
      treatment in Dar es Salaam, Tanzania.
AB  - INTRODUCTION: In Tanzania, the first case of H1N1/09 influenza was reported in
      September 2009. By March 2010, the reported number of cases was 770 with one
      death. Due to shortage of qualified human resources, essential medicines and
      laboratory supplies in health facilities, it was not known how well health-care
      providers in the country were prepared to deal with the pandemic. METHODOLOGY:
      The study was conducted from December 2009 to May 2010 in public hospitals and
      private community pharmacies in Dar es Salaam, Tanzania. Fifty-three prescribers
      and 200 dispensers were interviewed to assess their knowledge on the prevention
      and treatment of H1N1/09 influenza, and dissemination of correct information to
      the public regarding the pandemic. RESULTS: Most participants had inadequate
      knowledge on the transmission, prevention and management of H1N1/09 influenza.
      The majority of prescribers knew neither the antiviral drugs recommended for the
      treatment of H1N1 influenza (64%) nor their adverse effects (92.5%). The drug
      dispensers' knowledge was also inadequate regarding the transmission, prevention
      and treatment of H1N1/09 influenza. Forty-one (20.5%) salespersons without formal
      training in pharmaceutical or medical sciences were found dispensing and
      supervising the pharmacies. Most participants had misconceptions on how H1N1/09
      virus was transmitted. CONCLUSION: The results of the study revealed gaps in the
      knowledge of the health-care providers on the prevention and treatment of H1N1/09
      influenza infection. This indicates the need for strengthening of health-care
      systems and provision of continuing education and professional development for
      health-care providers on new and re-emerging diseases in the community.

PMID- 22421609
TI  - Predictive power of Koplik's spots for the diagnosis of measles.
AB  - INTRODUCTION: Measles is a major cause of mortality globally. In many countries,
      management of measles is based on clinical suspicion, but the predictive value of
      clinical diagnosis depends on knowledge and population prevalence of measles. In
      the pre-vaccine era with high measles incidence, Koplik's spots (KS) were said to
      be "pathognomonic". This study prospectively evaluated test properties and
      diagnostic odds ratios (OR) of KS. METHODOLOGY: Data including KS status were
      prospectively collected for a six-month period on all suspected measles cases
      reported to the North-West London Health Protection Unit. Saliva test kits were
      sent to all cases and KS test properties were analysed against measles
      confirmation by PCR or IgM testing (gold standard). RESULTS: The positive
      predictive value (PPV) of clinically suspecting measles was 50%. Using KS as
      diagnostic tool improved the PPV to 80% and the presence of KS was associated
      with confirmed measles in the multi-variable analysis (OR 7.2, 95% Confidence
      Interval 2.1-24.9, p=0.001). CONCLUSION: We found that Koplik's spots were highly
      predictive of confirmed measles and could be a good clinical tool to enable
      prompt measles management and control measures, as action often needs to be taken
      in the absence of laboratory confirmation. We suggest that current clinical case
      definitions might benefit from the inclusion of KS.

PMID- 22421610
TI  - Sexually transmitted infections in HIV-infected patients in Kabale Hospital,
      Uganda.
AB  - INTRODUCTION: Acquisition of sexually transmitted infections (STIs) is an
      epidemiological marker of high-risk sexual behavior in HIV-infected patients. We
      assessed the prevalence of STIs among patients attending an HIV care and support
      centre. METHODOLOGY: From January to August 2009, we assessed socio-demographic
      variables, sexuality, disclosure of sero-status and STI treatment for 400
      patients attending the HIV care and support centre. Characteristics of those who
      had been treated and those who had never been treated for STIs were compared to
      identify factors independently associated with STIs. RESULTS: Of the 400
      respondents, 25.3% were male, 47.3% were aged 25-34 years, over 85% were
      currently married or had ever been married, and 62% had primary level of
      education or less. Though 82.5% were on antiretroviral drugs, only 53.1%
      disclosed their sero-status to their regular partners and only 41.9% knew the
      sero-status of their regular partners. Furthermore, 151 (37.7%) had been treated
      for STIs. The STIs were gonorrhoea (15; 9.7%), chlamydia (11; 7.1%), Trichomonas
      vaginalis (5; 3.3%), syphilis (99; 64.3%), and mixed infections (21; 13.6%).
      Factors associated with STI treatment on univariable analysis were age at sexual
      debut, whether the respondent had had sex in the previous six months, frequency
      of sexual intercourse, having changed sexual partners, number of sexual partners,
      and age when the respondent had a first child. CONCLUSION: Unprotected sexual
      intercourse and STIs are common among patients seeking HIV care in Uganda. Only
      the age of sexual debut (odds ratio 0.82, confidence limits 0.71, 0.94) was
      independently (though inversely) associated with STIs.